PMID- 26193788
TI  - State of the field: Are the results of science contingent or inevitable?
AB  - This paper presents a survey of the literature on the problem of contingency in
      science. The survey is structured around three challenges faced by current
      attempts at understanding the conflict between "contingentist" and
      "inevitabilist" interpretations of scientific knowledge and practice. First, the
      challenge of definition: it proves hard to define the positions that are at stake
      in a way that is both conceptually rigorous and does justice to the plethora of
      views on the issue. Second, the challenge of distinction: some features of the
      debate suggest that the contingency issue may not be sufficiently distinct from
      other philosophical debates to constitute a genuine, independent philosophical
      problem. And third, the challenge of decidability: it remains unclear whether and
      how the conflict could be settled on the basis of empirical evidence from the
      actual history of science. The paper argues that in order to make progress in the
      present debate, we need to distinguish more systematically between different
      expressions that claims about contingency and inevitability in science can take.
      To this end, it introduces a taxonomy of different contingency and inevitability
      claims. The taxonomy has the structure of an ordered quadruple. Each contingency
      and each inevitability claim contains an answer to the following four questions:
      (how) are alternatives to current science possible, what types of alternatives
      are we talking about, how should the alternatives be assessed, and how different
      are they from actual science? 

PMID- 26193789
TI  - Collaborative explanation and biological mechanisms.
AB  - This paper motivates and outlines a new account of scientific explanation, which
      I term 'collaborative explanation.' My approach is pluralist: I do not claim that
      all scientific explanations are collaborative, but only that some important
      scientific explanations are-notably those of complex organic processes like
      development. Collaborative explanation is closely related to what philosophers of
      biology term 'mechanistic explanation' (e.g., Machamer et al., Craver, 2007). I
      begin with minimal conditions for mechanisms: complexity, causality, and
      multilevel structure. Different accounts of mechanistic explanation interpret and
      prioritize these conditions in different ways. This framework reveals two
      distinct varieties of mechanistic explanation: causal and constitutive. The two
      have heretofore been conflated, with philosophical discussion focusing on the
      former. This paper addresses the imbalance, using a case study of modeling
      practices in Systems Biology to reveals key features of constitutive mechanistic
      explanation. I then propose an analysis of this variety of mechanistic
      explanation, in terms of collaborative concepts, and sketch the outlines of a
      general theory of collaborative explanation. I conclude with some reflections on
      the connection between this variety of explanation and social aspects of
      scientific practice. 

PMID- 26193790
TI  - Re-orienting discussions of scientific explanation: A functional perspective.
AB  - Philosophy of science offers a rich lineage of analysis concerning the nature of
      scientific explanation, but the vast majority of this work, aiming to provide an
      analysis of the relation that binds a given explanans to its corresponding
      explanandum, presumes the proper analytic focus rests at the level of individual
      explanations. There are, however, other questions we could ask about explanation
      in science, such as: What role(s) does explanatory practice play in science?
      Shifting focus away from explanations, as achievements, toward explaining, as a
      coordinated activity of communities, the functional perspective aims to reveal
      how the practice of explanatory discourse functions within scientific communities
      given their more comprehensive aims and practices. In this paper, I outline the
      functional perspective, argue that taking the functional perspective can reveal
      important methodological roles for explanation in science, and consequently, that
      beginning here provides resources for developing more adequate responses to
      traditional concerns. In particular, through an examination of the ideal gas law,
      I emphasize the normative status of explanations within scientific communities
      and discuss how such status underwrites a compelling rationale for explanatory
      power as a theoretical virtue. 

PMID- 26193791
TI  - Collaborative explanation, explanatory roles, and scientific explaining in
      practice.
AB  - Scientific explanation is a perennial topic in philosophy of science, but the
      literature has fragmented into specialized discussions in different scientific
      disciplines. An increasing attention to scientific practice by philosophers is
      (in part) responsible for this fragmentation and has put pressure on criteria of
      adequacy for philosophical accounts of explanation, usually demanding some form
      of pluralism. This commentary examines the arguments offered by Fagan and Woody
      with respect to explanation and understanding in scientific practice. I begin by
      scrutinizing Fagan's concept of collaborative explanation, highlighting its
      distinctive advantages and expressing concern about several of its assumptions.
      Then I analyze Woody's attempt to reorient discussions of scientific explanation
      around functional considerations, elaborating on the wider implications of this
      methodological recommendation. I conclude with reflections on synergies and
      tensions that emerge when the two papers are juxtaposed and how these draw
      attention to critical issues that confront ongoing philosophical analyses of
      scientific explanation. 

PMID- 26193793
TI  - Network analysis of immunotherapy-induced regressing tumours identifies novel
      synergistic drug combinations.
AB  - Cancer immunotherapy has shown impressive results, but most patients do not
      respond. We hypothesized that the effector response in the tumour could be
      visualized as a complex network of interacting gene products and that by mapping
      this network we could predict effective pharmacological interventions. Here, we
      provide proof of concept for the validity of this approach in a murine
      mesothelioma model, which displays a dichotomous response to anti-CTLA4 immune
      checkpoint blockade. Network analysis of gene expression profiling data from
      responding versus non-responding tumours was employed to identify modules
      associated with response. Targeting the modules via selective modulation of hub
      genes or alternatively by using repurposed pharmaceuticals selected on the basis
      of their expression perturbation signatures dramatically enhanced the efficacy of
      CTLA4 blockade in this model. Our approach provides a powerful platform to
      repurpose drugs, and define contextually relevant novel therapeutic targets. 

PMID- 26193794
TI  - Identification of PblB mediating galactose-specific adhesion in a successful
      Streptococcus pneumoniae clone.
AB  - The pneumococcal genome is variable and there are minimal data on the influence
      of the accessory genome on phenotype. Pneumococcal serotype 14 sequence type (ST)
      46 had been the most prevalent clone causing pneumonia in children in Taiwan. A
      microarray was constructed using the genomic DNA of a clinical strain (NTUH-P15)
      of serotype 14 ST46. Using DNA hybridization, genomic variations in NTUH-P15 were
      compared to those of 3 control strains. Microarray analysis identified 7 genomic
      regions that had significant increases in hybridization signals in the NTUH-P15
      strain compared to control strains. One of these regions encoded PblB, a phage
      encoded virulence factor implicated (in Streptococcus mitis) in infective
      endocarditis. The isogenic pblB mutant decreased adherence to A549 human lung
      epithelial cell compared to wild-type NTUH-P15 strain (P = 0.01). Complementation
      with pblB restored the adherence. PblB is predicted to contain a galactose
      binding domain-like region. Preincubation of NTUH-P15 with D-galactose resulted
      in decreases of adherence to A549 cell in a dose-dependent manner. Challenge of
      mice with NTUH-P15, isogenic pblB mutant and pblB complementation strains
      determined that PblB was required for bacterial persistence in the nasopharynx
      and lung. PblB, as an adhesin mediating the galactose-specific adhesion activity
      of pneumococci, promote pneumococcal clonal success.

PMID- 26193795
TI  - Chemical Synthesis of the Epimeric (23R)- and (23S)-Fluoro Derivatives of Bile
      Acids via Horner-Wadsworth-Emmons Reaction.
AB  - A method for the synthesis of two (23R)- and (23S)-epimeric pairs of 23-fluoro
      3alpha,7alpha,12alpha-trihydroxy-5beta-cholan-24-oic acid and 23-fluoro
      3alpha,7alpha-dihydroxy-5beta-cholan-24-oic acid is described. The key
      intermediates, 23,24-dinor-22-aldehyde peracetates were prepared from cholic and
      chenodeoxycholic acids via the 24-nor-22-ene, 24-nor-22xi,23-epoxy, and 23,24
      dinor-22-aldehyde derivatives. The Horner-Wadsworth-Emmons reaction of the 23,24
      dinor-22-aldehydes using triethyl 2-fluoro-2-phosphonoacetate in the presence of
      LiCl and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), and subsequent hydrogenation
      of the resulting 23xi-fluoro-22-ene ethyl esters, followed by hydrolysis, gave a
      mixture of the epimeric (23R)- and (23S)-fluorinated bile acids which were
      resolved efficiently by preparative RP-HPLC. The stereochemical configuration of
      the fluorine atom at C-23 in the newly synthesized compounds was confirmed
      directly by the X-ray crystallographic data. The (1)H and (13)C NMR spectral
      differences between the (23R)- and (23S)-epimers were also discussed.

PMID- 26193796
TI  - Lymph node involvement by mycosis fungoides and Sezary syndrome mimicking
      angioimmunoblastic T-cell lymphoma.
AB  - Clinical management of cutaneous T-cell lymphoma (CTCL) and angioimmunoblastic T
      cell lymphoma (AITL) differs markedly. Diagnostic distinction is critical.
      Herein, we describe a series of 4 patients with clinically, molecularly, and
      histopathologically annotated mycosis fungoides or Sezary syndrome whose nodal
      disease mimicked AITL. The patients otherwise exhibited classic clinical
      manifestations of mycosis fungoides/Sezary syndrome preceding the onset of
      lymphadenopathy by 1 to 5 years. Skin biopsies revealed epidermotropic
      infiltrates characteristic of CTCL. Lymph node biopsies revealed dense CD4+ T
      cell infiltrates that coexpressed follicular helper T-cell markers and were
      accompanied by proliferations of high endothelial venules and arborizing CD21+
      follicular dendritic cell networks. Two patients had T-cell receptor gene
      rearrangement studies performed on their skin, lymph node, and peripheral blood
      demonstrating identical polymerase chain reaction clones in all 3 tissues. A
      small secondary clonal B-cell population was present in 1 patient that mimicked
      the B-cell proliferations known to accompany AITL and persisted on successive
      nodal biopsies over several years. This latter phenomenon has not previously been
      described in CTCL. The potential for patients to be misdiagnosed with AITL for
      lack of consideration of advanced-stage CTCL with nodal involvement underscores
      the necessity of information sharing among the various pathologists and
      clinicians involved in the care of each patient. 

PMID- 26193797
TI  - Upregulation of Abelson interactor protein 1 predicts tumor progression and poor
      outcome in epithelial ovarian cancer.
AB  - Abelson interactor protein 1 (Abi1) is a key regulator of actin reorganization
      and lamellipodia formation. Because of its role in cell migration, Abi1 has been
      implicated in tumor progression. In the present study, we investigated the role
      of Abi1 in epithelial ovarian cancer (EOC) by analyzing its expression and
      correlation with clinicopathological and survival data. We evaluated the
      expression of Abi1 in 223 paraffin-embedded EOC specimens by immunohistochemistry
      and 46 frozen EOC samples by Western blot and real-time reverse transcription
      polymerase chain reaction analysis. Results showed that Abi1 protein and mRNA
      expression was significantly higher in EOC tissue compared with noncancerous
      tumors and normal ovaries (P < .05). Moreover, high level of Abi1 expression was
      significantly correlated with advanced stage, high grade, elevated Ca-125 level,
      and suboptimal surgical debulking (P < .05). By Western blot analysis, Abi1 was
      expressed in highly invasive cells compared with weakly invasive cells (P < .05).
      Immunofluorescence was performed to demonstrate Abi1 expression in SKOV3 cells.
      Additionally, upregulation of Abi1 significantly correlated with shorter survival
      (P < .05). Most importantly, multivariate analysis showed that Abi1
      overexpression is an independent prognostic factor, complementary to clinical
      stage and residual tumor size. In conclusion, our findings suggest that Abi1 acts
      as a tumor-promoting gene in EOC progression, which may lead to unfavorable
      prognosis. Abi1 may serve as a potential effective prognostic marker for EOC. 

PMID- 26193798
TI  - Use of Community Assessments for Public Health Emergency Response (CASPERs) to
      Rapidly Assess Public Health Issues - United States, 2003-2012.
AB  - INTRODUCTION: Community Assessment for Public Health Emergency Response (CASPER)
      is an epidemiologic technique designed to provide quick, inexpensive, accurate,
      and reliable household-based public health information about a community's
      emergency response needs. The Health Studies Branch at the Centers for Disease
      Control and Prevention (CDC) provides in-field assistance and technical support
      to state, local, tribal, and territorial (SLTT) health departments in conducting
      CASPERs during a disaster response and in non-emergency settings. Data from
      CASPERs conducted from 2003 through 2012 were reviewed to describe uses of
      CASPER, ascertain strengths of the CASPER methodology, and highlight significant
      findings. METHODS: Through an assessment of the CDC's CASPER metadatabase, all
      CASPERs that involved CDC support performed in US states and territories from
      2003 through 2012 were reviewed and compared descriptively for differences in
      geographic distribution, sampling methodology, mapping tool, assessment settings,
      and result and action taken by decision makers. RESULTS: For the study period, 53
      CASPERs were conducted in 13 states and one US territory. Among the 53 CASPERS,
      38 (71.6%) used the traditional 2-stage cluster sampling methodology, 10 (18.8%)
      used a 3-stage cluster sampling, and two (3.7%) used a simple random sampling
      methodology. Among the CASPERs, 37 (69.9%) were conducted in response to specific
      natural or human-induced disasters, including 14 (37.8%) for hurricanes. The
      remaining 16 (30.1%) CASPERS were conducted in non-disaster settings to assess
      household preparedness levels or potential effects of a proposed plan or program.
      The most common recommendations resulting from a disaster-related CASPER were to
      educate the community on available resources (27; 72.9%) and provide services
      (18; 48.6%) such as debris removals and refills of medications. In preparedness
      CASPERs, the most common recommendations were to educate the community in
      disaster preparedness (5; 31.2%) and to revise or improve preparedness plans (5;
      31.2%). Twenty-five (47.1%) CASPERs documented on the report or publications the
      public health action has taken based on the result or recommendations. Findings
      from 27 (50.9%) of the CASPERs conducted with CDC assistance were published in
      peer-reviewed journals or elsewhere. CONCLUSION: The number of CASPERs conducted
      with CDC assistance has increased and diversified over the past decade. The
      CASPERs' results and recommendations supported the public health decisions that
      benefitted the community. Overall, the findings suggest that the CASPER is a
      useful tool for collecting household-level disaster preparedness and response
      data and generating information to support public health action.

PMID- 26193799
TI  - Mitogen-activated protein kinase-activated protein kinase 2 is a critical
      regulator of pig oocyte meiotic maturation.
AB  - Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2), a
      direct substrate of p38 MAPK, plays key roles in multiple cellular processes. In
      the present study, we showed that MK2 affected not only cumulus expansion, but
      also the oocyte meiotic cell cycle in porcine oocytes. Inhibition of MK2 arrested
      oocytes at the germinal vesicle (GV) stage or the prometaphase I/metaphase I
      stage. Unlike in mouse oocytes, where phosphorylated (p-) MK2 was localised at
      the minus end of spindle microtubules and close to the spindle poles, in porcine
      oocytes p-MK2 was concentrated at the spindle equator and localised at the plus
      end of spindle microtubules. Knockdown or inhibition of MK2 resulted in spindle
      defects: spindles were surrounded by irregular chromosome non-disjunction or by
      chromosomes detached from the spindles. MK2 regulated spindle organisation and
      chromosome alignment by connecting microtubules with kinetochores. In addition,
      unlike in mitotic cells and meiotic mouse oocytes, the MK2-p38 MAPK pathway may
      not play an important role during meiotic cell cycle in porcine oocytes. In
      conclusion, MK2 is an important regulator of porcine oocyte meiotic maturation.

PMID- 26193800
TI  - Residents in distress: an exploration of assistance-seeking and reporting
      behaviors.
AB  - BACKGROUND: This study explores assistance-seeking and reporting behaviors in
      surgical residents faced with stressful circumstances. METHODS: Three surgical
      societies distributed a multiple choice, free-text response survey to residents.
      RESULTS: One hundred sixty-four residents (39% male) responded; 58% of women (43%
      men) were married; and 22% of men (7% women) were international medical
      graduates. Residents' dominant action to colleagues' concerning behavior was to
      approach him/her directly. Women were more likely to report colleagues'
      unpredictable behavior toward staff (28% vs 10%, P < .05), alcohol on breath at
      work (53% vs 32%, P = nonsignificant), and personal hygiene deterioration (15% vs
      2%, P < .05) to an authority. Men were more likely to ignore frequent
      interpersonal conflicts and illnesses. CONCLUSIONS: Male and female surgery
      residents adopt different strategies in dealing with perceived distress in their
      colleagues. These impact their response to signs of impairment. Educators should
      consider sex while providing residents with an understanding of their role in the
      recognition of personal impairment and that of their peers.

PMID- 26193801
TI  - Surgery in high-volume hospitals not commission on cancer accreditation leads to
      increased cancer-specific survival for early-stage lung cancer.
AB  - BACKGROUND: Quality of oncologic outcomes is of paramount importance in the care
      of patients with non-small cell lung cancer (NSCLC). We sought to evaluate the
      relationship of hospital volume for lobectomy on cancer-specific survival in
      NSCLC patients treated in California, as well as the influence of Commission on
      Cancer (CoC) accreditation. METHODS: The California Cancer Registry was queried
      from 2004 to 2011 for cases of Stage I NSCLC and 8,345 patients were identified.
      Statistical analysis was used to determine prognostic factors for cancer-specific
      survival. RESULTS: A total of 7,587 patients were treated surgically. CoC
      accreditation was not significant for cancer-specific survival, but treatment in
      high-volume centers was associated with longer survival when compared with low-
      and medium-volume centers (hazard ratio 1.77, 1.474 to 2.141 and hazard ratio
      1.23, 1.058 to 1.438). CONCLUSION: These data suggest that surgical treatment in
      high-volume hospitals is associated with longer cancer-specific survival for
      early-stage NSCLC, but that CoC accreditation is not.

PMID- 26193802
TI  - Risk of seizures in children with tectal gliomas.
AB  - The objective of this study was to determine the prevalence of seizures in
      children with tectal gliomas and to determine if there are common clinical,
      electroencephalography (EEG), or radiologic findings that predict risk of
      seizures in these patients. We conducted a retrospective review of all patients
      with tectal gliomas over a 22-year period at a single institution. Data
      extraction included sex, age at presentation of tectal glioma and age of
      presentation with seizures, magnetic resonance imaging (MRI) findings, seizure
      frequency and semiology, and EEG findings. We identified 79 patients, 66 of whom
      had adequate imaging and clinical data for further analysis. Eight patients
      (12.1%) had a history of seizures. Three patients had a clear symptomatic cause
      of seizures. Three patients were diagnosed with a tectal glioma as an incidental
      finding after a first seizure. One patient had a history of febrile convulsions.
      One patient had a generalized seizure 5 years after presenting with macrocephaly.
      Although the risk of seizure in children with known tectal glioma was relatively
      high, we did not identify specific clinical, radiologic, EEG, or MRI features
      that are predictive of increased risk. Thus, in children with tectal gliomas who
      have seizures, alternative causes for the seizures must be sought.

PMID- 26193803
TI  - Behavioral Changes in General Practitioners towards Chronic Obstructive Pulmonary
      Disease Over Five Years: An Observational Study.
AB  - OBJECTIVE: Early detection of chronic obstructive pulmonary disease (COPD) is
      critical for preventing progression; however, the disease is rarely detected in
      the early stages. One reason for this is that COPD is not generally recognized
      and diagnosed by general practitioners (GPs). The objective of this study was to
      observe changes in the knowledge and behavior of GPs regarding the diagnosis and
      treatment of COPD over a five-year period. METHODS: The surveys were performed
      using identical and anonymous questionnaires in 2005, 2006 and 2010. During this
      period, various educational campaigns were conducted. MATERIALS: All members of
      the Shiga Medical Association working as GPs in Shiga Prefecture. RESULTS: The
      number of questionnaires collected was 216 of 711, 269 of 731 and 326 of 856,
      respectively. Throughout the study period, the number of doctors who prescribed
      inhaled long-acting muscarinic antagonists (LAMAs) significantly increased
      (p<0.001). However, there were no significant changes in the rate of possession
      of spirometers or recognition of COPD guidelines. When we focused on the data for
      internists, the rate of recognition of the guidelines increased significantly
      (p<0.01), despite a lack of change in the rate of possession of spirometers.
      Furthermore, the results of the multivariate analysis revealed that increased
      knowledge concerning COPD was associated with the doctor's specialty, ownership
      of a spirometer, number of COPD patients attending their clinic and their level
      of recognition of the guidelines. CONCLUSION: During the study period, the GPs
      prescribed more inhaled LAMAs. The rate of recognition of COPD guidelines was
      also increased among internists. Educational campaigns may be more effective if
      the backgrounds of the GPs are taken into consideration.

PMID- 26193804
TI  - Erratum to "AWAJI criteria are not always superior to the previous criteria: A
      meta-analysis" by Jae-Sik Jang and Jong Seok Bae, published in the June 2015
      issue of Muscle & Nerve (Muscle Nerve. 51[6]:822-829 DOI:10.1002/mus.24575 and
      Epub 2015 Mar 31).

PMID- 26193810
TI  - Sarcoplasmic Reticulum Phospholipid Fatty Acid Composition and Sarcolipin Content
      in Rat Skeletal Muscle.
AB  - In a previous study, we reported lower sarcoplasmic reticulum (SR) Ca(2+) pump
      ionophore ratios in rat soleus compared to red and white gastrocnemius (RG, WG)
      muscles which may be indicative of greater SR Ca(2+) permeability in soleus. Here
      we assessed the lipid composition of the SR membranes obtained from these muscles
      to determine if SR docosahexaenoic acid (DHA) content and fatty acid unsaturation
      could help to explain the previously observed differences in SR Ca(2+)
      permeability. Since we have shown previously that sarcolipin may also influence
      SR Ca(2+) permeability, we also examined the levels of sarcolipin in rat muscle.
      We found that SR membrane DHA content was significantly higher in soleus (5.3 +/-
      0.2 %) compared to RG (4.2 +/- 0.2 %) and WG (3.3 +/- 0.2 %). Likewise, total SR
      membrane unsaturation and unsaturation index (UI) were significantly higher in
      soleus (% unsaturation: 59.1 +/- 2.4; UI: 362.9 +/- 0.8) compared to RG (%
      unsaturation: 55.3 +/- 1.0; UI: 320.9 +/- 2.5) and WG (% unsaturation: 52.6 +/-
      1.1; UI: 310. +/- 2.2). Sarcolipin protein was 17-fold more abundant in rat
      soleus compared to RG and was not detected in WG; however, comparisons between
      soleus, RG, and WG in sarcolipin-null mice revealed that, in the absence of
      sarcolipin, ionophore ratios are still lowest in soleus and highest in WG.
      Overall, our results suggest that SR membrane DHA content and unsaturation, and,
      in part, sarcolipin expression may contribute to SR Ca(2+) permeability and, in
      turn, may have implications in muscle-based metabolism and diet-induced obesity.

PMID- 26193811
TI  - Treatments for erectile dysfunction in spinal cord patients: alternatives to
      phosphodiesterase type 5 inhibitors? A review study.
AB  - STUDY DESIGN: Review study. OBJECTIVES: Alternative treatments to oral
      phosphodiesterase type 5 inhibitors (PDE5Is) in individuals with spinal cord
      lesions (SCLs) and erectile dysfunction (ED). SETTING: Italy. METHODS: Research
      clinical trials (1999-2014). RESULTS: Twelve studies were selected. One article
      documented that 76% of subjects reached satisfactory sexual intercourse (SI)
      using intracavernosal injection of vasoactive medications (papaverine and
      prostaglandin E1). One study regarding perineal training showed a significant
      increase (P<0.05) in penile tumescence in 10 individuals with preserved sacral
      segment. Two studies reported contrasting results on erectile function (EF) using
      various dosages of oral fampridine (25-40 mg). Furthermore, 95.1% of patients on
      fampridine 25 mg experienced drawbacks. Disappointing findings were found with
      intraurethral alprostadil (125-1000 MUg) and sublingual apomorphine 3 mg. Two
      studies concerning penile prosthesis reported valid SI more than 75% of the time
      with a mean follow-up of 11 years, although around 15% of individuals showed side
      effects. As for surgical treatments, 88% of males submitted to Brindley sacral
      anterior root stimulator after sacral dorsal rhizotomy achieved valid erection up
      to 8 years following the procedure. Three studies documented the impact of
      definitive sacral neuromodulation implant (Medtronic, Minneapolis, MN, USA) also
      on EF. After surgery, 20-37.5% of patients with ED recovered normal EF.
      CONCLUSIONS: Data are scant on the efficacy of ED treatments for SCL subjects who
      did not respond to PDE5Is. Further research should investigate the effects of any
      SCL treatments even when they are not strictly used for neurogenic sexual
      dysfunction.

PMID- 26193812
TI  - A cost-effectiveness analysis of long-term intermittent catheterisation with
      hydrophilic and uncoated catheters.
AB  - STUDY DESIGN: Cost-effectiveness analysisObjective:To establish a model to
      investigate the cost effectiveness for people with spinal cord injury (SCI), from
      a lifetime perspective, for the usage of two different single-use catheter
      designs: hydrophilic-coated (HC) and uncoated (UC). The model includes the long
      term sequelae of impaired renal function and urinary tract infection (UTI).
      SETTING: Analysis based on a UK perspective. METHODS: A probabilistic Markov
      decision model was constructed, to compare lifetime costs and quality-adjusted
      life years, taking renal and UTI health states into consideration, as well as
      other catheter-related events. UTI event rates for the primary data set were
      based on data from hospital settings to ensure controlled and accurate reporting.
      A sensitivity analysis was applied to evaluate best- and worst-case scenarios.
      RESULTS: The model predicts that a 36-year-old SCI patient with chronic urinary
      retention will live an additional 1.4 years if using HC catheters compared with
      UC catheters, at an incremental cost of L2100. Moreover, the lifetime number of
      UTI events will be reduced by 16%. All best- and worst-case estimates were within
      the UK threshold of being cost effective. CONCLUSION: The use of HC catheters for
      intermittent catheterisation in SCI patients is highly cost effective. The
      outcome is consistent irrespective of whether UTI data are collected in hospital
      or community settings.

PMID- 26193813
TI  - Functional assessment of SCI patients by FIM: yes or no?

PMID- 26193814
TI  - Return-to-work intentions during spinal cord injury rehabilitation: an audit of
      employment outcomes.
AB  - STUDY DESIGN: Single-centre, retrospective cohort study. OBJECTIVES: To analyse
      the return-to-work intentions during spinal cord injury (SCI) rehabilitation.
      SETTING: Tertiary care, spinal cord injury rehabilitation unit, National Spinal
      Injuries Centre, Stoke Mandeville Hospital, Ayelsbury, UK. METHODS: Employment
      outcomes were obtained from the Needs Assessment Checklist (NAC), for all
      patients admitted to the unit between February 2008 and October 2014. NAC1 is
      completed within 4 weeks post-mobilisation and NAC2 upon the patient moving to
      the pre-discharge ward. Data from 362 participants were analysed for return-to
      work intentions, by gender, age and injury severity. RESULTS: Seventy-six percent
      of the sample population was employed at the time of their injury. At NAC1, 22.4%
      of individuals had made plans to return to work, whereas 44.2% had not; at NAC2,
      34.3% had made plans to return to work and 31.2% had not. This difference was
      found to be statistically significant. There were significant differences in
      return-to-work intentions by injury severity at NAC1 but not NAC2, and by age
      group at NAC2 but not NAC1. CONCLUSION: Less than half of those employed at the
      time of their injury had made plans to return to work before their discharge from
      the unit. The low proportion of individuals with SCI returning to work--just one
      in three--is concerning in view of the lost health and psychosocial benefits, and
      requires greater prominence during rehabilitation. Future research into effective
      employment interventions to improve employment outcomes in this population is
      required.

PMID- 26193815
TI  - A telephone-based version of the spinal cord injury-secondary conditions scale: a
      reliability and validity study.
AB  - OBJECTIVE: The objective of this study was to determine the inter-rater
      reliability and validity of using a telephone-based version of the spinal cord
      injury-secondary conditions scale (SCI-SCS). TRIAL DESIGN: A psychometric study
      was conducted. SETTING: The study was conducted in Royal North Shore Hospital,
      Sydney, Australia. PARTICIPANTS: Forty people with a complete or an incomplete
      spinal cord injury. METHODS: Inter-rater reliability was tested by comparing the
      telephone-based version of the SCI-SCS administered on two different days by two
      different telephone assessors. Validity was tested by comparing the telephone
      based version of the SCI-SCS with the paper-based version of the SCI-SCS.
      RESULTS: The median (interquartile range) age and time since injury were 54 (48
      63) years and 28 (14-35) years, respectively. The intraclass correlation
      coefficient (95% confidence interval) reflecting the agreement between the
      telephone-based version of the SCI-SCS administered on two different days by two
      different assessors was 0.96 (0.93-0.98). The corresponding value reflecting
      agreement between the telephone-based assessment and the paper-based assessment
      was 0.90 (0.83-0.95). CONCLUSION: The telephone-based version of the SCI-SCS is a
      simple and a quick questionnaire to administer that has both inter-rater
      reliability and validity. It may be useful as a way to screen for secondary
      health conditions in low- and middle-income countries where it is not always
      feasible to provide routine face-to-face follow-ups and where literacy may be a
      problem.

PMID- 26193816
TI  - The influence of orthotic gait training with an isocentric reciprocating gait
      orthosis on the walking ability of paraplegic patients: a pilot study.
AB  - OBJECTIVES: The aim of this study was to evaluate the influence of walking with
      an isocentric reciprocating gait orthosis (IRGO) by spinal cord injury (SCI)
      patients on walking speed, distance walked and energy consumption whilst
      participating in a 12-week gait re-training program. METHODS: Six people with
      motor complete SCI (mean age 29 years, weight 63 kg and height 160 cm with injury
      levels ranging from T8 to T12) participated in this study. Gait evaluation was
      performed at baseline and after 4, 8 and 12 weeks. Walking speed and heart rate
      were measured to calculate the resulting physiological cost index (PCI). RESULTS:
      Reductions in energy consumption were observed after 4, 8 and 12 weeks compared
      with baseline but were not significant. However, walking distance increased
      significantly (P=0.010, P=0.003 and P=0.005, respectively) and also did so during
      the 8-12-week period (P=0.013). Walking speed also improved, but not
      significantly. CONCLUSION: Intensive gait training with the IRGO improved walking
      speed and the distance walked by paraplegics, as well as reducing the PCI of
      walking, as compared with baseline during the whole 12-week period. This
      indicates that further improvements in these parameters may be expected when
      utilizing gait training longer than 8 weeks.

PMID- 26193817
TI  - Effectiveness of transcranial direct current stimulation for the management of
      neuropathic pain after spinal cord injury: a meta-analysis.
AB  - OBJECTIVES: To conduct a systematic review and meta-analysis to examine the
      effect of transcranial direct current stimulation (tDCS) on reducing neuropathic
      pain intensity in individuals with spinal cord injury (SCI). METHODS: Medline,
      CINAHL, EMBASE and PsycINFO databases were searched for all relevant articles
      published from 1980 to November 2014. Trials were included if (i) tDCS
      intervention group and a placebo control group were present; (ii) at least 50% of
      participants in the study had an SCI and there were at least three participants;
      (iii) participants were aged 18 years or older; and (iv) persistent pain for at
      least 3 months. Studies were excluded if: (i) the tDCS intervention group was
      compared with an active treatment group; (ii) there was insufficient reporting
      detail to enable pooling of data; and (iii) it was a nonclinical trial (that is,
      reviews, epidemiology, basic sciences). A standardized mean difference (SMD) +/-
      s.e. and 95% confidence interval (CI) was calculated for each outcome of interest
      and the results were pooled using a fixed or random effects model, as
      appropriate. Effect sizes were interpreted as: small > 0.2, moderate > 0.5, large
      > 0.8. RESULTS: Five studies met inclusion criteria of which four were randomized
      controlled trials and one was a prospective controlled trial. The pooled analysis
      found a significant effect of tDCS on reducing neuropathic pain after SCI post
      treatment (SMD = 0.510 +/- 0.202; 95% CI, 0.114-0.906; P < 0.012); however, this
      effect was not maintained at follow-up (SMD = 0.353 +/- 0.272; 95% CI, -0.179 to
      0.886; P < 0.194). A reduction of 1.33 units on a 10-item scale was observed post
      treatment. No significant adverse events were reported. CONCLUSION: Meta-analytic
      results indicate a moderate effect of tDCS in reducing neuropathic pain among
      individuals with SCI; however, the effect was not maintained at follow-up. A mean
      pooled decrease of 1.33 units on a 10-item scale was found post treatment.
      Several factors were implicated in the effectiveness of tDCS in reducing pain.
      Due to the limited number of studies and lack of follow-up, more evidence is
      required before treatment recommendations can be made.

PMID- 26193818
TI  - Strong electric fields at a prototypical oxide/water interface probed by ab
      initio molecular dynamics: MgO(001).
AB  - We report a density-functional theory (DFT)-based study of the interface of bulk
      water with a prototypical oxide surface, MgO(001), and focus our study on the
      often-overlooked surface electric field. In particular, we observe that the bare
      MgO(001) surface, although charge-neutral and defectless, has an intense electric
      field on the A scale. The MgO(001) surface covered with 1 water monolayer (1 ML)
      is investigated via a supercell accounting for the experimentally-observed (2 *
      3) reconstruction, stable at ambient temperature, and in which two out of six
      water molecules are dissociated. This 1 ML-hydrated surface is also found to have
      a high, albeit short-ranged, normal component of the field. Finally, the
      oxide/water interface is studied via room-temperature ab initio molecular
      dynamics (AIMD) using 34 H2O molecules between two MgO(001) surfaces. To our best
      knowledge this is the first AIMD study of the MgO(001)/liquid water interface in
      which all atoms are treated using DFT and including several layers above the
      first adsorbed layer. We observe that the surface electric field, averaged over
      the AIMD trajectories, is still very strong on the fully-wet surface, peaking at
      about 3 V A(-1). Even in the presence of bulk-like water, the structure of the
      first layer in contact with the surface remains similar to the (2 * 3)
      reconstructed ice ad-layer on MgO(001). Moreover, we observe proton exchange
      within the first layer, and between the first and second layers - indeed, the O-O
      distances close to the surface are found to be distributed towards shorter
      distances, a property which has been shown to directly promote proton transfer. 

PMID- 26193819
TI  - Using decision lists to construct interpretable and parsimonious treatment
      regimes.
AB  - A treatment regime formalizes personalized medicine as a function from individual
      patient characteristics to a recommended treatment. A high-quality treatment
      regime can improve patient outcomes while reducing cost, resource consumption,
      and treatment burden. Thus, there is tremendous interest in estimating treatment
      regimes from observational and randomized studies. However, the development of
      treatment regimes for application in clinical practice requires the long-term,
      joint effort of statisticians and clinical scientists. In this collaborative
      process, the statistician must integrate clinical science into the statistical
      models underlying a treatment regime and the clinician must scrutinize the
      estimated treatment regime for scientific validity. To facilitate meaningful
      information exchange, it is important that estimated treatment regimes be
      interpretable in a subject-matter context. We propose a simple, yet flexible
      class of treatment regimes whose members are representable as a short list of if
      then statements. Regimes in this class are immediately interpretable and are
      therefore an appealing choice for broad application in practice. We derive a
      robust estimator of the optimal regime within this class and demonstrate its
      finite sample performance using simulation experiments. The proposed method is
      illustrated with data from two clinical trials. 

PMID- 26193820
TI  - Morphology, microstructure, crystallography, and chemistry of distinct CaCO3
      deposits formed by early recruits of the scleractinian coral Pocillopora
      damicornis.
AB  - Scleractinian corals begin their biomineralization process shortly after larval
      settlement with the formation of calcium carbonate (CaCO(3)) structures at the
      interface between the larval tissues and the substrate. The newly settled larvae
      exert variable degrees of control over this skeleton formation, providing an
      opportunity to study a range of biocarbonate structures, some of which are
      transient and not observed in adult coral skeletons. Here we present a
      morphological, structural, crystallographic, and chemical comparison between two
      types of aragonite deposits observed during the skeletal development of 2-days
      old recruits of Pocillopora damicornis: (1) Primary septum and (2) Abundant,
      dumbbell-like structures, quasi-randomly distributed between initial deposits of
      the basal plate and not present in adult corals-At the mesoscale level, initial
      septa structures are formed by superimposed fan-shaped fasciculi consisting of
      bundles of fibers, as also observed in adult corals. This organization is not
      observed in the dumbbell-like structures. However, at the ultrastructural level
      there is great similarity between septa and dumbbell components. Both are
      composed of <100 nm granular units arranged into larger single-crystal
      domains.Chemically, a small difference is observed between the septae with an
      average Mg/Ca ratio around 11 mmol/mol and the dumbbell-like structures with ca.
      7 mmol/mol; Sr/Ca ratios are similar in the two structures at around 8 mmol/mol
      Overall, the observed differences in distribution, morphology, and chemistry
      between septa, which are highly conserved structures fundamental to the
      architecture of the skeleton, and the transient, dumbbell-like structures,
      suggest that the latter might be formed through less controlled biomineralization
      processes. Our observations emphasize the inherent difficulties involved in
      distinguishing different biomineralization pathways based on ultrastructural and
      crystallographical observations.

PMID- 26193821
TI  - Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8
      that recruits inflammatory monocytes.
AB  - Lamina propria (LP) macrophages are constantly exposed to commensal bacteria, and
      are refractory to those antigens in an interleukin (IL)-10-dependent fashion.
      However, the mechanisms that discriminate hazardous invasion by bacteria from
      peaceful co-existence with them remain elusive. Here we show that CD169(+)
      macrophages reside not at the villus tip, but at the bottom-end of the LP
      microenvironment. Following mucosal injury, the CD169(+) macrophages recruit
      inflammatory monocytes by secreting CCL8. Selective depletion of CD169(+)
      macrophages or administration of neutralizing anti-CCL8 antibody ameliorates the
      symptoms of experimentally induced colitis in mice. Collectively, we identify an
      LP-resident macrophage subset that links mucosal damage and inflammatory monocyte
      recruitment. Our results suggest that CD169(+) macrophage-derived CCL8 serves as
      an emergency alert for the collapse of barrier defence, and is a promising target
      for the suppression of mucosal injury. 

PMID- 26193822
TI  - Scanning electron microscopy of antennal sensory organs of the cattle grub,
      Hypoderma lineatum (Diptera: Oestridae).
AB  - Hypoderma lineatum (Villers, 1789) (Diptera: Oestridae) is a hypodermosis fly
      that has resulted in great economic losses worldwide. The antennae of cattle grub
      males and females were examined through stereoscopic microscopy and scanning
      electron microscopy to reveal the general morphology, combined with distribution,
      type, size, and ultrastructure of the antennal sensilla. All of the three
      antennal segments (antennal scape, pedicel, and funiculus) possess microtrichiae
      on their surface. Mechanoreceptors only exist on the antennal scape and pedicel.
      The antennal funiculus presents four types of antennal sensilla: trichoid,
      basiconic, coeloconic, and clavate sensilla. Three distinctive characters of H.
      lineatum are obvious: (1) the relatively slender, flexible, and equal-height
      mechanoreceptors; (2) the enlarged antennal pedicel, and numerous antennal
      sensory pits and pit sensilla on the antennal funiculus; and (3) all types of
      antennal sensilla clustered in sensory pits, respectively. Additionally, the
      enlarged antennal pedicel and abundant sensory pits and pit sensilla might
      facilitate odor detection, enhance olfactory sensitivity and accuracy, and also
      protect the fragile antennal sensilla from mechanical irritation or damage. 

PMID- 26193823
TI  - Prevalence and diversity of avian malaria parasites in migratory Black Skimmers
      (Rynchops niger, Laridae, Charadriiformes) from the Brazilian Amazon Basin.
AB  - The Medium Solimoes River region in the Brazilian Amazon Basin is an area
      utilized for reproduction and nesting by a variety of species of migratory
      aquatic birds such as Black Skimmers (Rynchops niger). These migratory birds form
      mixed-species reproductive colonies with high population densities and exhibit a
      large range of migration routes. This study aimed to describe the prevalence and
      diversity of the avian malaria parasites Plasmodium and Haemoproteus in Black
      Skimmers, on the basis of the association between microscopic observation of
      blood smears and amplification of the mitochondrial cytochrome b gene (mtDNA cyt
      b). The overall prevalence rates of the parasites for juvenile and adult bird
      specimens were 16% (5/31) and 22% (15/68), respectively. Sequencing the mtDNA cyt
      b marker revealed two Plasmodium lineages, which had been previously described in
      different regions of the American continent, including a Neotropical region in
      Southeast Brazil, and one Haemoproteus lineage. The fact that avian malarial
      parasites have been found infecting the Black Skimmers in the Brazilian Amazon
      ecosystem, which exhibits considerable diversity, highlights the importance of
      these migratory birds as a potential source of infection and dispersion of
      pathogens to other susceptible birds of the Nearctic and Neotropical regions.

PMID- 26193824
TI  - Parasites of fish larvae: do they follow metabolic energetic laws?
AB  - Eumetazoan parasites in fish larvae normally exhibit large body sizes relative to
      their hosts. This observation raises a question about the potential effects that
      parasites might have on small fish. We indirectly evaluated this question using
      energetic metabolic laws based on body volume and the parasite densities. We
      compared the biovolume as well as the numeric and volumetric densities of
      parasites over the host body volume of larval and juvenile-adult fish and the
      average of these parasitological descriptors for castrator parasites and the
      parasites found in the fish studied here. We collected 5266 fish larvae using
      nearshore zooplankton sampling and 1556 juveniles and adult fish from intertidal
      rocky pools in central Chile. We considered only the parasitized hosts: 482 fish
      larvae and 629 juvenile-adult fish. We obtained 31 fish species; 14 species were
      in both plankton and intertidal zones. Fish larvae exhibited a significantly
      smaller biovolume but larger numeric and volumetric densities of parasites than
      juvenile-adult fish. Therefore, fish larvae showed a large proportion of parasite
      biovolume per unit of body host (cm(3)). However, the general scaling of
      parasitological descriptors and host body volume were similar between larvae and
      juvenile-adult fish. The ratio between the biovolume of parasites and the host
      body volume in fish larvae was similar to the proportion observed in castrator
      parasites. Furthermore, the ratios were different from those of juvenile-adult
      fish, which suggests that the presence of parasites implies a high energetic cost
      for fish larvae that would diminish the fitness of these small hosts. 

PMID- 26193825
TI  - The association between obesity and oligoclonal band formation in multiple
      sclerosis patients.
AB  - Since some neurological disorders present with increased body-mass index (BMI)
      and cerebrospinal fluid (CSF) oligoclonal bands (OCB), obesity-induced
      inflammation has been previously speculated in formation of OCB. We investigated
      the association between BMI, OCB formation and clinical features of MS in 120
      patients with relapsing remitting multiple sclerosis (RRMS), a disease with high
      OCB positivity incidence. Thirty RRMS patients had BMI>=30 and 100 patients
      displayed CSF OCB. OCB positive and negative patients had comparable BMI and
      weight values. Disease duration, annual attack number and EDSS were not
      correlated with BMI and body weight. Patients with normal and high BMI did not
      significantly differ by means of OCB positivity, gender, annual attack number,
      disease duration and EDSS scores. Our results argue against a possible role of
      obesity in OCB formation. Moreover, obesity does not appear to influence
      disability and clinical progression of MS patients. 

PMID- 26193826
TI  - Correlating intracellular nonviral polyplex localization with transfection
      efficiency using high-content screening.
AB  - High-content screening (HCS) has gained interest in cellular imaging because of
      its ability to provide statistically significant data from multiple parameters
      simultaneously in cell-based assays. Although HCS has been mainly used in drug
      discovery, it has other potentially useful applications, such as elucidating the
      processes involved in nonviral gene vector-mediated gene delivery, as was
      explored in this study. HCS was used to measure transfection efficiency and
      cytotoxicities of polyplexes made from fluorescently labeled polyethylenimine
      (PEI) and pDNA encoding EGFP (pEGFP-N1). The results generated using HCS were
      confirmed using more conventional and labor-intensive methods. For the first
      time, a relationship between transfected cells and the number of polyplexes in
      the cytoplasm was shown. Four to five polyplex signals were found in the
      cytoplasm of successfully transfected cells, whilst nontransfected cells harbored
      less than one polyplex signal within the cytoplasm. HCS has the potential to be
      used as a tool in the field of gene delivery. HCS can not only simultaneously
      measure transfection efficiency and cytotoxicity of various nonviral gene
      vectors; it can also be used to track such vectors through various subcellular
      compartments.

PMID- 26193827
TI  - A randomized controlled clinical trial of a nurse-led structured psychosocial
      intervention program for people with first-onset mental illness in psychiatric
      outpatient clinics.
AB  - This study aimed to test the effectiveness of a nurse-led structured psychosocial
      intervention program in Chinese patients with first-onset mental illness. A
      single-blind, parallel group, randomized controlled trial design was used. The
      study involved 180 participants with mild to moderate-severe symptoms of
      psychotic or mood disorders who were newly referred to two psychiatric outpatient
      clinics in Hong Kong. Patients were randomly assigned to either an eight-session
      nurse-led psychosocial intervention program (plus usual care) or usual
      psychiatric outpatient care (both n=90). The primary outcome was psychiatric
      symptoms. Outcomes were measured at recruitment, one week and 12 months post
      intervention. Patients in the psychosocial intervention group reported
      statistically significant improvements in symptoms compared to treatment as
      usual. There were also significant improvements in illness insight and perceived
      quality of life and reduction in length of re-hospitalizations over the 12-month
      follow-up. The findings provide evidence that the nurse-led psychosocial
      intervention program resulted in improved health outcomes in Chinese patients
      with first-onset mental illness. 

PMID- 26193828
TI  - Association analysis of the HLA-DRB1*01 and HLA-DRB1*04 with schizophrenia by tag
      SNP genotyping in the Japanese population.

PMID- 26193829
TI  - [Influence of active commuting on happiness, well-being, psychological distress
      and body shape in adolescents].
AB  - OBJECTIVE: To analyse the association between active commuting to secondary
      school and indicators of psychological health in a sample of 1012 adolescents.
      METHOD: Active commuting was assessed through a questionnaire, subjective
      happiness with the Subjective Happiness Scale, well-being and psychological
      distress with the General Well-Being Scale, and body shape was assessed using the
      short version of the Body Shape Questionnaire. RESULTS: Adolescents who spent
      more than 15 minutes per day actively commuting to secondary school had higher
      levels of subjective happiness (p=0.032) and psychological well-being (p=0.021)
      and lower levels of psychological distress (p=0.021) than adolescents who spent
      15 minutes or less per day. There were no differences in body shape between less
      and more active adolescents (p >0.05). CONCLUSION: Active commuting to secondary
      school for more of 15 minutes per day is recommended because it is associated
      with higher levels of happiness and well-being in adolescents.

PMID- 26193830
TI  - Cepharanthine mitigates lung injury in lower limb ischemia-reperfusion.
AB  - BACKGROUND: Oxidation and inflammation caused by lower limb ischemia-reperfusion
      (I/R) readily induce lung injury. We elucidated whether cepharanthine, a potent
      antioxidative and anti-inflammatory drug, can mitigate lung injury induced by
      lower limb I/R. Role of heme oxygenase 1 (HO-1) was also investigated. MATERIALS
      AND METHODS: Adult male Sprague-Dawley rats were randomized to receive I/R, I/R
      plus cepharanthine, or I/R plus cepharanthine plus the HO-1 activity inhibitor
      tin protoporphyrin (SnPP; n = 12 in each group). Sham control groups were run
      simultaneously. I/R was induced by applying rubber band tourniquets high around
      each thigh for 3 h followed by reperfusion for 24 h. RESULTS: Rats receiving I/R
      had significant increases in concentrations of nitric oxide, malondialdehyde
      (lipid peroxidation marker), and inflammatory molecules (including interleukin 6,
      macrophage inflammatory protein 2, and prostaglandin E2) in plasma, and the
      lungs, indicating that I/R caused significant oxidation and inflammation in rats.
      Rats receiving I/R also had significant increases in concentration of
      phosphorylated inhibitor-kappaB, indicating that I/R caused significant nuclear
      factor kappaB activation. Assays of arterial blood gas, biochemistry, and
      histopathology confirmed that I/R-induced significant lung injury in rats.
      Cepharanthine significantly reduced the oxidation, inflammation, nuclear factor
      kappaB activation, and lung injury induced by I/R. Of note, cepharanthine
      significantly enhanced pulmonary HO-1 expression after I/R. Moreover, these
      previously mentioned effects of cepharanthine were partially reversed by
      inhibiting the activity of HO-1. CONCLUSIONS: Cepharanthine mitigates lung injury
      induced by bilateral lower limb I/R in rats. The mechanisms may involve its
      effects on reducing oxidation and inflammation. The mechanisms may also involve
      enhancing HO-1 expression.

PMID- 26193831
TI  - Appendectomy increased the risk of ischemic heart disease.
AB  - BACKGROUND: Although the appendix may not be considered vital, recent studies
      have noted adverse health consequences after appendectomy. This study aimed to
      use a population-based data set to explore whether appendectomy increases the
      risk for subsequent ischemic heart disease (IHD) in a 3-y follow-up period.
      MATERIALS AND METHODS: This study used data from the Longitudinal Health
      Insurance Database 2000 in Taiwan. The study cohort included 5413 patients who
      underwent appendectomies. The comparison cohort was selected by randomly
      recruiting 16,239 enrollees matched with the study group in terms of sex, age,
      hypertension, hyperlipidemia, and diabetes. Each individual was tracked for 3 y
      to identify whether he and/or she developed IHD during the follow-up period. Cox
      proportional hazard regressions were performed for analysis. RESULTS: During a 3
      y follow-up, 196 (3.62%) and 375 (2.31%) IHD incidents developed in the study and
      the comparison cohorts, respectively. For adults aged >=18 y, experiencing an
      appendectomy was independently associated with a 1.54-fold increased risk of IHD
      during the 3 y of follow-up (95% CI = 1.29-1.84). The association persisted in
      further analyses stratified by age. CONCLUSIONS: There is an increased risk of
      subsequent IHD within 3 y after appendectomy, and this underscores the need for
      more serious clinical decision-making in removing the appendix. Regular
      monitoring for IHDs is also recommended for patients who have undergone an
      appendectomy.

PMID- 26193832
TI  - Mesenchymal stem cells reverse trauma and hemorrhagic shock-induced bone marrow
      dysfunction.
AB  - BACKGROUND: Lung contusion (LC) followed by hemorrhagic shock (HS) causes
      persistent bone marrow (BM) dysfunction lasting up to 7 d after injury.
      Mesenchymal stem cells (MSCs) are multipotent cells that can hasten healing and
      exert protective immunomodulatory effects. We hypothesize that MSCs can attenuate
      BM dysfunction after combined LCHS. MATERIALS AND METHODS: Male Sprague-Dawley
      rats (n = 5-6 per group) underwent LC plus 45 min of HS (mean arterial pressure
      of 30-35). Allogeneic MSCs (5 * 10(6) cells) were injected intravenously after
      resuscitation. At 7 d, BM was analyzed for cellularity and growth of
      hematopoietic progenitor cell (HPC) colonies (colony-forming unit-erythroid;
      burst-forming unit-erythroid; and colony-forming unit-granulocyte, erythrocyte,
      monocyte, megakaryocyte). Flow cytometry measured %HPCs in peripheral blood;
      plasma granulocyte colony-stimulating factor (G-CSF) levels were measured via
      enzyme-linked immunosorbent assay. Data were analyzed by one-way analysis of
      variance followed by the Tukey multiple comparison test. RESULTS: As previously
      shown, at 7 d, LCHS resulted in 22%, 30%, and 24% decreases in colony-forming
      unit-granulocyte, erythrocyte, monocyte, megakaryocyte, burst-forming unit
      erythroid, and colony-forming unit-erythroid colony growth, respectively, versus
      naive. Treatment with MSCs returned all BM parameters to naive levels. There was
      no difference in %HPCs in peripheral blood between groups; however, G-CSF
      remained increased up to 7 d after LCHS. MSCs returned G-CSF to naive levels.
      Plasma from animals receiving MSCs was not suppressive to the BM. CONCLUSIONS:
      One week after injury, the persistent BM dysfunction observed in animals
      undergoing LCHS is reversed by treatment with MSCs with an associated return of
      plasma G-CSF levels to normal. Plasma from animals undergoing LCHS plus MSCs was
      not suppressive to BM cells in vitro. Treatment with MSCs after injury and shock
      reverses BM suppression and returns plasma G-CSF levels to normal.

PMID- 26193833
TI  - Characterization and assessment of contaminated soil and groundwater at an
      organic chemical plant site in Chongqing, Southwest China.
AB  - Contamination from organic chemical plants can cause serious pollution of soil
      and groundwater ecosystems. To characterize soil contamination and to evaluate
      the health risk posed by groundwater at a typical organic chemical plant site in
      Chongqing, China, 91 soil samples and seven groundwater samples were collected.
      The concentrations of different contaminants and their three-dimensional
      distribution were determined based on the 3D-krige method. Groundwater chemistry
      risk index (Chem RI) and cancer risk were calculated based on TRIAD and RBCA
      models. The chemistry risk indices of groundwater points SW5, SW18, SW22, SW39,
      SW52, SW80, and SW82 were 0.4209, 0.9972, 0.9324, 0.9990, 0.9991, 1.0000, and
      1.0000, respectively, indicating that the groundwater has poor environmental
      status. By contrast, the reference Yangtse River water sample showed no pollution
      with a Chem RI of 0.1301. Benzene and 1,2-dichloroethane were the main
      contaminants in the groundwater and were responsible for the elevated cancer
      risk. The cumulative health risk of groundwater points (except SW5 and SW18) were
      all higher than the acceptable baselines of 10(-6), which indicates that the
      groundwater poses high cancer risk. Action is urgently required to control and
      remediate the risk for human health and groundwater ecosystems. 

PMID- 26193834
TI  - Trace Elements in Water, Sediments and the Elongate Tigerfish Hydrocynus
      forskahlii (Cuvier 1819) from Lake Turkana, Kenya Including a Comprehensive
      Health Risk Analysis.
AB  - This study presents the distribution of 17 major and trace elements in surface
      water, sediments and fish tissues from Lake Turkana, Kenya. Eight sediment and
      ten water samples from the west bank of the lake, as well as 34 specimens of the
      elongate tigerfish Hydrocynus forskahlii caught in that region were examined. It
      is the first report for Li, Rb, Sr, Mo from the lake and the first report on most
      of the trace elements for this fish species. The concentrations of elements in
      the water and sediments showed no sign of pollution. In fish muscle, Li, Zn and
      Cd showed relatively high abundances, with mean concentrations of 206, 427 and
      0.56 mg/kg dw, respectively. The calculated target hazard quotient values for Li,
      Zn, Sr and Cd were 138.7, 1.9, 4.1 and 0.76, respectively; therefore the
      consumption of these fish poses a health risk to humans in the area.

PMID- 26193835
TI  - Persistence of Pendimethalin in/on Wheat, Straw, Soil and Water.
AB  - Pendimethalin, a dinitroaniline group of organic herbicide compounds used as pre
      emergence weed control in wheat, onion and soyabean crops in India. The
      experiments were designed to study the harvest time residues of pendimethalin in
      wheat grain and straw its dissipation behaviour in soil and water. At harvest
      time, the residues of pendimethalin in wheat grain and straw were found to be
      below determination limit of 0.001 mg kg(-1) following single application of the
      herbicide at the rate of 1 (T1/single dose) and 2 (T2/double dose) kg a.i. ha(
      1). Soil samples from the field were collected periodically and analysed by GC
      ECD system. In soil, initial deposits of 4.069 and 10.473 mg kg(-1) of
      pendimethalin persisted up to 90 days and dissipation followed first order
      kinetics with half life period of 12.03 days in T1 and 13.00 days in T2. Residues
      of pendimethalin studied in water under laboratory conditions at 0.5 (T1) and 1.0
      (T2) mg L(-1) levels persisted up to 90 days. Dissipation kinetics followed first
      order kinetics with half-life values of 12.70 and 13.78 days at single and double
      dose, respectively. Limit of determination in grain, straw and soil were 0.001 mg
      kg(-1) and in water was 0.001 mg L(-1). Application of the herbicide is
      considered quite safe from consumer and environmental point of view. 

PMID- 26193836
TI  - Acute Toxicity of Endosulfan to the Non-target Organisms Hyalella curvispina and
      Cnesterodon decemmaculatus.
AB  - Pesticide consumption in Argentina has steadily increased over the last two
      decades, while one of these compounds, namely endosulfan, is commonly found in
      environmental samples. Also the fish Cnesterodon decemmaculatus and the amphipod
      Hyalella curvispina are widely distributed in agricultural areas of southern
      South America. The aim of the present contribution was therefore to determine the
      acute toxicity of endosulfan to both organisms, and compare it with species
      sensitivity distributions (SSD) and measured field concentrations. The 48 h-LC50
      (with 95 % confidence limits) were 1.8 (1.6-2.1) ug/L for C. decemmaculatus and
      16.4 (15.1-17.7) ug/L for H. curvispina. C. decemmaculatus was more sensitive
      than 74 % of fish based on the SSD. Endosulfan concentrations in stream water
      reported in the literature were often higher than the C. decemmaculatus LC50. It
      may hence be concluded that C. decemmaculatus is a suitable sentinel organism for
      ecotoxicological risk assessment in South America.

PMID- 26193837
TI  - Metals Bioaccumulation Mechanism in Neem Bark.
AB  - The aim of this work was to define the bioaccumulation mechanism of metals onto
      the non-living biomaterial prepared from an extensively available plant bark
      biomass of neem (Azadirachta indica). Based on maximum ultimate fixation
      capacities (mmol/g) of the product, metals ions could be arranged as Hg(2+) <
      Cd(2+) < Pb(2+) ? Cu(2+). Surface properties of the biomaterial were
      characterized by X-ray photoelectron spectroscopy and X-ray diffraction
      techniques for their sorption mechanism. Whewellite (C2CaO4 . H2O) was identified
      in the biomaterial, which indicated that calcium ions are electrovalently bonded
      with carboxylate ions facilitating the ion exchange mechanism with metal ions.
      Bioaccumulation of metal ions was also studied by Fourier transform infrared
      spectroscopy, which indicated the presence of functional groups implicated in
      adsorbing metal ions. Biomaterial did not adsorb anionic As(III), As(V) and
      Cr(VI), because of their electrostatic repulsion with carboxylic functional
      groups. Neem bark can be used as bioindicators, bioaccumulators and biomonitors
      while determining environmental pressures. Metal bioaccumulative properties and
      structural investigation of plant bark has potential in providing quantitative
      information on the metal contamination in the surrounding environment.

PMID- 26193838
TI  - Theory of fracture formation in a heterogeneous fibrillar membrane.
AB  - We present a statistical model of fracture in hierarchical structured
      heterogeneous materials. We describe the material as a network of fibre bundles.
      The time to fracture is analytically derived as a function of the bundle size and
      the local stress. This provides a straightforward criterium for material
      selection. The original framework here proposed proves versatile: it can be
      adapted to various practical specific cases upon tuning of its parameters which
      corresponds to experimentally measurable quantities. 

PMID- 26193839
TI  - Insights into the consequences of co-polymerisation in the early stages of IAPP
      and Abeta peptide assembly from mass spectrometry.
AB  - The precise molecular mechanisms by which different peptides and proteins
      assemble into highly ordered amyloid deposits remain elusive. The fibrillation of
      human amylin (also known as islet amyloid polypeptide, hIAPP) and the amyloid
      beta peptide (Abeta-40) are thought to be pathogenic factors in Type 2 diabetes
      mellitus (T2DM) and Alzheimer's disease (AD), respectively. Amyloid diseases may
      involve co-aggregation of different protein species, in addition to the self
      assembly of single precursor sequences. Here we investigate the formation of
      heterogeneous pre-fibrillar, oligomeric species produced by the co-incubation of
      hIAPP and Abeta-40 using electrospray ionisation-ion mobility spectrometry-mass
      spectrometry (ESI-IMS-MS)-based methods. Conformational properties and gas-phase
      stabilities of amyloid oligomers formed from hIAPP or Abeta40 alone, and from a 1
      : 1 mixture of hIAPP and Abeta40 monomers, were determined and compared. We show
      that co-assembly of the two sequences results in hetero-oligomers with distinct
      properties and aggregation kinetics properties compared with the homo-oligomers
      present in solution. The observations may be of key significance to unravelling
      the mechanisms of amyloid formation in vivo and elucidating how different
      sequences and/or assembly conditions can result in different fibril structures
      and/or pathogenic outcomes. 

PMID- 26193840
TI  - The value of cytoplasmic Y-box-binding protein 1 as a prognostic marker for
      breast cancer in Korean.
AB  - BACKGROUND: The human Y-box-binding protein 1 (YB-1) is a member of the DNA/RNA
      binding family of proteins that regulates transcription and translation of genes.
      Previous studies suggest that YB-1 may have an oncogenic role in various cancers.
      In this study, we evaluate the prognostic value of cytoplasmic YB-1 with respect
      to breast cancer. METHODS: Immunohistochemical staining study was performed with
      YB-1 using tissue block from 233 patients with invasive ductal carcinoma.
      Patients were divided into two groups according to expression of cytoplasmic YB-1
      in tumor cell (high versus low). The relationship between the expression of YB-1,
      clinicopathological characteristics and breast cancer prognosis was analyzed.
      RESULTS: Hormone receptor negativity, worse histologic and nuclear grade, high
      tumor stage, lymphovascular invasion and high Ki67 (>=14 %) were related with the
      increased expression of cytoplasmic YB-1 in tumor cell (p < 0.05). Although there
      was no significant difference in relapse-free survival (RFS) between the two
      groups (p = 0.412), difference in overall survival (OS) was statistically
      significant (p = 0.035). In multivariate analysis for OS, YB-1 was an independent
      prognostic factor (p = 0.043). CONCLUSION: This suggests that the increased
      expression of cytoplasmic YB-1 in tumor cells can be regarded as an independent
      prognostic factor for breast cancer, related to poor prognostics. Expression of
      cytoplasmic YB-1 in cancer cell could be used as an independent prognostic marker
      for predicting OS in breast cancer.

PMID- 26193841
TI  - Effect of tamoxifen and fulvestrant long-term treatments on ROS production and
      (pro/anti)-oxidant enzymes mRNA levels in a MCF-7-derived breast cancer cell
      line.
AB  - BACKGROUND: Reactive oxygen species (ROS) are key players in the apoptotic
      effects induced by short-term tamoxifen treatment of breast cancer cells, but
      also in acquired resistance following long-term treatment. Whereas the use of the
      selective estrogen receptor down-regulator fulvestrant is promising, especially
      in patients who develop tamoxifen resistance, only few studies addressed its
      implication in the modulation of cellular redox status. METHODS: The regulation
      of (pro/anti)-oxidant players were first investigated at the mRNA level in a MCF
      7-derived cell line after short-term (24 h) estradiol treatment. Long-term anti
      estrogen treated MCF-7 derived cell lines were also developed: 3 months of 4
      hydroxytamoxifen alone (MCF7L-OHTLT) or followed by 3 months of fulvestrant
      (MCF7L-ICILT). Growth properties, hormone sensitivity, receptor content, ROS
      production and relative mRNA expression of pro or antioxidant enzymes were
      evaluated in these long-term treated cell lines. RESULTS: Short-term estradiol
      treatment showed a hormone sensitivity of Nox2, GPx1, GPx2 and SOD1 mRNA levels.
      The long-term fulvestrant treatment (3 months) of MCF7L-OHTLT led to a reduced
      level of ROS production accompanied with a drastic drop of the accessory protein
      p22(phox) mRNA. This ROS reduction, although not clearly related to antioxidant
      enzymes level, seems to be involved in fulvestrant sensitivity of long-term anti
      estrogen treated cells, as suggested by the effects of antiradical tempol
      treatment. CONCLUSION: When compared to long-term 4-hydroxytamoxifen-treated
      breast cancer cells, addition of fulvestrant treatment was able to diminish ROS
      production and p22(phox) mRNA level, and made cells more sensitive to growth
      inhibition induced by tempol. These effects may be a valuable asset of the
      fulvestrant treatment.

PMID- 26193842
TI  - The Adult Life After Childhood Cancer in Scandinavia (ALiCCS) Study: Design and
      Characteristics.
AB  - BACKGROUND: During the last five decades, survival of childhood cancer has
      increased from 25% to 80%. At the same time, however, it has become evident that
      survivors experience a broad range of therapy-related late adverse health
      effects. The aim of the Adult Life after Childhood Cancer in Scandinavia (ALiCCS)
      study is to investigate long-term health consequences of past and current
      therapies in order to improve follow-up care of survivors and to reduce treatment
      related morbidity of future patients. PROCEDURE: Childhood cancer survivors were
      identified through the five Nordic cancer registries and a comparison cohort was
      established through random selection of cancer-free individuals from the civil
      registration systems. A unique personal identification number was used to link
      between different health registries. Abstraction of treatment information for a
      subset of survivors allows investigation of the association between the various
      components of cancer therapy and late occurring comorbidity. RESULTS: The
      childhood cancer survivor cohort comprises 33,160 1-year survivors and the
      comparison cohort comprises 212,892 cancer free individuals from the general
      population. In the childhood cancer survivor cohort, all types of childhood
      cancer are represented including leukemia (21%), lymphoma (14%), central nervous
      system tumors (24%), sarcomas (5%), retinoblastoma (3%), and neuroblastoma (4%).
      Among the survivors, 22% have been followed beyond the age of 40 years.
      CONCLUSION: The ALiCCS study constitutes a new large resource for research on
      late effects of childhood cancers that include all types of childhood
      malignancies and has followed a large proportion of the survivors well into late
      adulthood.

PMID- 26193843
TI  - Osteogenesis imperfecta type III and hypogonadotropic hypogonadism result in
      severe bone loss: a case report.
AB  - We present the case of a 33-year-old male patient with multiple fractures and
      typical radiographical and clinical characteristics of osteogenesis imperfecta
      (OI) type III. Furthermore, the patient has suffered from hypogonadotropic
      hypogonadism since childhood. On the basis of antiresorptive therapy, no further
      fractures occurred within several years. Recently, recurrent nontraumatic
      fractures without bone healing were observed. Decreased bone mineral density was
      assessed by dual X-ray absorptiometry (DXA). High-resolution peripheral
      quantitative computed tomography (HR-pQCT) showed impaired trabecular bone
      structure. Due to recurrent fragility fractures and severe deterioration of bone
      structure, an osteoanabolic treatment with teriparatide was initiated to
      potentially stimulate fracture healing and to increase bone formation. 

PMID- 26193844
TI  - 'Pre-entry screening for tuberculosis' commentary: authors' response.

PMID- 26193845
TI  - Want a better way to control antibiotic resistance? Fight the corruption.

PMID- 26193846
TI  - A simple and gentle technique for reduction after anterior shoulder dislocation.
AB  - BACKGROUND: Anterior shoulder dislocation (ASD) is a common sports injury. The
      goal of this study was to evaluate a new procedure for reduction after ASD with
      respect to success rate, the need for medication for muscle relaxation, sedation,
      and application of pain medication and put it into context to a systematic
      literature review. PATIENTS AND METHODS: We retrospectively evaluated the new
      method in 263 patients in an Austrian skiing area from December 2005 till April
      2009. We included patients with unilateral ASD and excluded those with a combined
      trauma and consecutive admission to hospital. RESULTS: The new procedure is
      performed in a supine position, the therapist takes the patients hand of the
      injured limb with his one hand and with his other hand counter holds against the
      acromion. Then he enhances the traction on the upper limp by using his trunk as a
      kind of fulcrum. With eye contact and instructions to relax, the therapist is
      able to detect the muscular tension, so that he can adjust the amount of traction
      accordingly. The presented procedure was successful in all reported cases. For
      196 patients (74.5 %) no medication for muscle relaxation, sedation, or pain
      medication were needed. CONCLUSION: The new method is a promising option to
      popular techniques for reduction of anterior shoulder dislocations. The benefits
      of this protocol are a gentle and simple application of the procedure as well as
      an easy acquisition.

PMID- 26193847
TI  - Radiologic healing of lateral femoral wall fragments after intramedullary nail
      fixation for A3.3 intertrochanteric fractures.
AB  - INTRODUCTION: Intramedullary nail fixation is a useful treatment option for A3
      intertrochanteric fractures. Occasionally, we have encountered displaced lateral
      femoral wall (LFW) fragment during surgery with intramedullary nail system. We
      investigated the postoperative spontaneous reduction of displaced LFW fragments
      without further fixation and the factors that affected the spontaneous reduction
      of displaced LFW fragments. MATERIALS AND METHODS: Forty-four patients with A3.3
      intertrochanteric fracture were treated by surgery using intramedullary nails
      (PFNA; Synthes, Paoli) between March 2007 and December 2012. All patients had a
      minimum follow-up period of 12 months. We calculated the amount of spontaneous
      reduction of the displaced LFW fragments from immediate postoperative and last
      follow-up anteroposterior radiographs. We measured the tilting angle of the LFW
      fragment, tip-apex distance (TAD), and telescoping of the blade, and evaluated
      the quality of postoperative reduction. RESULTS: Twenty-five of the 44 patients
      had displaced LFW fragments, and the average amount of spontaneous reduction of
      the displaced LFW fragment was 4.8 mm with statistical significance (p = 0.005).
      The average tilting angle of all patients was -4.97 degrees , telescoping was
      6.83 mm, and TAD was 19.77 mm. Twenty-one patients had good quality of reduction,
      21 had acceptable quality, and 2 had poor quality. Multivariate logistic
      regression analysis for these factors indicated that tilting angle was the only
      significant factor related to spontaneous reduction of a displaced LFW fragment
      (p = 0.007, odds ratio = 1.336). CONCLUSIONS: In intramedullary nailing of A3.3
      intertrochanteric fractures, the displaced LFW fragments tend to reduce
      spontaneously without any additional fixation during the postoperative period. We
      conclude that no additional fixation is needed for the displaced LFW fragment
      after surgery with intramedullary nail.

PMID- 26193848
TI  - A novel implant-free tibial pull-press-fixation for ACL reconstruction.
AB  - INTRODUCTION: Extracortical fixation techniques in anterior cruciate ligament
      reconstruction bear the risk of tunnel enlargement, while close-to-aperture
      fixations often show lower failure loads. The purpose for this study was to
      investigate the biomechanical benefits of a novel implant-free combination of an
      extra-cortical and close-to-aperture fixation. MATERIALS AND METHODS: Quadrupled
      human cadaveric semitendinosus tendons were fixed to 30 porcine tibiae with
      either a cannulated interference screw (I), an implant-free post-fixation (S), or
      a novel pull-press fixation (P). Specimens were cyclically loaded 20 times
      between 20 and 60 N followed by 500 cycles with 60-200 N, followed by a load-to
      failure test with 1 mm/s. RESULTS: The mean elongation of the tendons in the P
      group during the 500 cycles between 60 and 200 N was significantly lower (5.69 +/
      2.16 mm) compared to 9.20 +/- 3.21 mm in S-group and 9.37 +/- 3.1 mm in the I
      group (p < 0.05). The mean maximum load-to-failure was significantly higher in
      the P-group (728.2 +/- 76.4 N) compared to 476.4 +/- 68.8 N in the S-group and
      625.9 +/- 82.5 N in the I-group (p < 0.05). Stiffness of the constructs in the P
      group was significantly higher (121.7 +/- 44.9 N/mm) compared to 46.2 +/- 17.7
      N/mm in the S- and 72.8 +/- 29.8 N/mm in the I-group (p < 0.03). CONCLUSIONS:
      This study indicates superior biomechanical properties of a novel implant-free
      tibial pull-press fixation to conventional implant-free and close-to-aperture
      interference screw fixations in terms of cyclic elongation and maximum load-to
      failure. LEVEL OF EVIDENCE: Not applicable, basic science study.

PMID- 26193849
TI  - Mind the gap: An empirical study of post-trial access in HIV biomedical
      prevention trials.
AB  - The principle of providing post-trial access for research participants to
      successful products of that research is widely accepted and has been enshrined in
      various declarations and guidelines. While recent ethical guidelines recognise
      that the responsibility to provide post-trial access extends to sponsors,
      regulators and government bodies as well as to researchers, it is the researchers
      who have the direct duty of care to participants. Researchers may thus need to
      act as advocates for trial participants, especially where government bodies,
      sponsors, and regulatory bodies have complex interests vested in decisions about
      whether or not new interventions are made available, how, and to whom. This paper
      provides an empirical account of post-trial access in the context of HIV
      prevention research. It describes both access to the successful products of
      research and the provision antiretroviral drugs for trial participants who
      acquire HIV. First, we provide evidence that, in the current system, there is
      considerable variation in the duration and timeliness of access. We then argue
      that by analysing the difficulties faced by researchers to this point, and their
      efforts to meet this obligation, much can be learned about how to secure post
      trial access in HIV biomedical preventions trials. While researchers alone have a
      limited obligation, their advocacy on behalf of trial participants may be
      necessary to call the other parties to account. 

PMID- 26193850
TI  - Morphological and Structural Evolutions of Metal-Organic Framework Particles from
      Amorphous Spheres to Crystalline Hexagonal Rods.
AB  - Compositions as well as morphologies and structures of particles are vital
      factors that define their properties and applications. However, the morphology
      and structure changes associated with the composition change of metal-organic
      frameworks (MOFs) are barely studied. Herein, we report the morphology and
      structure changes of MOF particles associated with the ratio of two organic
      linkers incorporated within MOF particles, when they are constructed from the
      reactions of In(NO3)3 in the presence of isophthalic acid (H2IPA) and/or 1,4
      benzenedicarboxylic acid (H2BDC). Two tendencies-the tendency of BDC and In(3+)
      to form porous crystalline hexagonal rods, and the tendency of IPA and In(3+) to
      form non-porous amorphous spherical particles-compete during the formation of MOF
      particles. Eventually, the incorporated ratio of BDC and IPA within the MOF
      particles, and thus their morphology and porosity, are controlled by altering the
      relative amounts of H2BDC and H2IPA used during the reactions.

PMID- 26193851
TI  - Early detection of cytomegalovirus-specific cytotoxic T lymphocytes against
      cytomegalovirus antigenemia in human leukocyte antigen haploidentical
      hematopoietic stem cell transplantation.
AB  - Human leukocyte antigen (HLA)-haploidentical stem cell transplantation (haplo
      SCT) is associated with a high incidence of cytomegalovirus (CMV) infection,
      probably originating from the delayed reconstitution of CMV-specific T cell
      immunity. There have been few reports on the presence of CMV-specific cytotoxic T
      lymphocytes (CMV-CTLs) after haplo-SCT. We have studied CMV-specific immune
      reconstitution by measuring the absolute number of CMV-CTLs using a flow
      cytometry method with HLA-A2-restricted NLVPMVATV peptide dextramers. We examined
      the association between reconstitution patterns of CMV-CTLs and the duration of
      CMV antigenemia in 15 patients who underwent first allogeneic SCT from HLA
      haploidentical-related donors with HLA-A2. In seven and eight patients, CMV
      antigenemia consecutively resolved for more than 4 weeks (the CMV antigenemia
      'resolved' group) and intermittently persisted (the CMV antigenemia 'persistent'
      group) during a 100-day observation period, respectively. The group of the seven
      patients, in whom levels of CMV antigenemia were reduced to zero, had a
      significantly lower maximum level of CMV antigenemia than the CMV antigenemia
      persistent group. In contrast, the CMV antigenemia persistent group had a
      significantly higher maximum level of CMV-CTLs, but the levels took longer to
      peak. Despite no difference in general lymphocyte recovery between the two
      groups, the CMV antigenemia resolved group had significantly higher median CMV
      CTL counts than the CMV antigenemia persistent group at 6 weeks after onset of
      CMV infection. Flow cytometry analysis of CMV-CTLs is a convenient method of
      monitoring reconstitution of CMV-specific lymphocyte immunity following haplo
      SCT. 

PMID- 26193852
TI  - Antiviral prophylaxis in patients with solid tumours and haematological
      malignancies--update of the Guidelines of the Infectious Diseases Working Party
      (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).
AB  - Reactivation of viral infections is common in patients with solid tumour or
      haematological malignancy. Incidence and severity depend on the extent of
      cellular immunosuppression. Antiviral prophylaxis may be effective to prevent
      viral reactivation. In 2006, the Infectious Diseases Working Party of German
      Society for Hematology and Medical Oncology (DGHO) published guidelines for
      antiviral prophylaxis in these patient populations. Here, we present an update of
      these guidelines for patients with solid and haematological malignancies
      undergoing antineoplastic treatment but not allogeneic stem cell transplantation.
      Relevant literature for reactivation of different viruses (herpes simplex virus
      (HSV), varicella zoster virus (VZV), hepatitis B virus (HBV) and respiratory
      viruses) is discussed to provide evidence-based recommendations for clinicians
      taking care of this patient population. We recommend a risk-adapted approach with
      (val)acyclovir against HSV and VZV in patients treated with alemtuzumab,
      bortezomib or purine analogues. Seasonal vaccination against influenza is
      recommended for all patients with solid or haematological malignancies regardless
      of antineoplastic therapy. Hepatitis B screening is recommended in
      lymphoproliferative disorders, acute leukaemia, and breast cancer, and during
      treatment with monoclonal anti-B-cell antibodies, anthracyclines, steroids and in
      autologous stem cell transplantation. In those with a history of hepatitis B
      prophylactic lamivudine, entecavir or nucleotide analogues as adefovir are
      recommended to prevent reactivation. 

PMID- 26193853
TI  - Characterisation of Atherogenic Effects of Low Carbohydrate, High Protein Diet
      (LCHP) in ApoE/LDLR-/- Mice.
AB  - INTRODUCTION: Low Carbohydrate High Protein diet represents a popular strategy to
      achieve weight loss. OBJECTIVE: The aim of this study was to characterize effects
      of low carbohydrate, high protein diet (LCHP) on atherosclerotic plaque
      development in brachiocephalic artery (BCA) in apoE/LDLR-/- mice and to elucidate
      mechanisms of proatherogenic effects of LCHP diet. MATERIALS AND METHODS:
      Atherosclerosis plaques in brachiocephalic artery (BCA) as well as in aortic
      roots, lipoprotein profile, inflammation biomarkers, expression of SREBP-1 in the
      liver as well as mortality were analyzed in Control diet (AIN-93G) or LCHP (Low
      Carbohydrate High Protein) diet fed mice. RESULTS: Area of atherosclerotic
      plaques in aortic roots or BCA from LCHP diet fed mice was substantially
      increased as compared to mice fed control diet and was characterized by increased
      lipids and cholesterol contents (ORO staining, FT-IR analysis), increased
      macrophage infiltration (MOMA-2) and activity of MMPs (zymography). Pro
      atherogenic phenotype of LCHP fed apoE/LDLR-/- mice was associated with increased
      plasma total cholesterol concentration, and in LDL and VLDL fractions, increased
      TG contents in VLDL, and a modest increase in plasma urea. LCHP diet increased
      SCD-1 index, activated SREBP-1 transcription factor in the liver and triggered
      acute phase response as evidence by an increased plasma concentration of
      haptoglobin, CRP or AGP. Finally, in long-term experiment survival of apoE/LDLR-/
      mice fed LCHP diet was substantially reduced as compared to their counterparts
      fed control diet suggesting overall detrimental effects of LCHP diet on health.
      CONCLUSIONS: The pro-atherogenic effect of LCHP diet in apoE/LDLR-/- mice is
      associated with profound increase in LDL and VLDL cholesterol, VLDL
      triglicerides, liver SREBP-1 upregulation, and systemic inflammation.

PMID- 26193854
TI  - Serum Polyunsaturated Fatty Acid Composition and Serum High-Sensitivity C
      Reactive Protein Levels in Healthy Japanese Residents: The KOBE Study.
AB  - BACKGROUND/OBJECTIVES: Serum polyunsaturated fatty acid (PUFA) composition
      reflects dietary intake and is related to risks for cardiovascular diseases. We
      hypothesized that serum n-3 PUFA composition, especially including long-chain n-3
      PUFA such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is
      associated with inflammatory status, which is related to increased risk for
      cardiovascular diseases. SUBJECTS/METHODS: We investigated the relationship
      between serum PUFA composition and high-sensitivity C-reactive protein (hs-CRP)
      levels in a cross-sectional study among 1,102 healthy men and women aged 40-74
      years who reside in Kobe City. Multiple linear regression models that predict hs
      CRP level were prepared to confirm the contribution of serum total n-3 PUFA, long
      chain n-3 PUFA, EPA and DHA compositions after adjusting for other PUFAs and
      atherosclerotic risk factors. RESULTS: The serum n-3 PUFA, particularly long
      chain n-3 PUFA, compositions were inversely associated with the hs-CRP levels.
      The standardized regression coefficient was -0.089 (p < 0.01) for total n-3 PUFA,
      -0.091 (p < 0.01) for long-chain n-3 PUFA, -0.071 (p = 0.03) for EPA, and -0.068
      (p = 0.04) for DHA. The n-6 PUFA compositions were also inversely associated with
      the hs-CRP levels (-0.169 [p < 0.01] for total n-6 PUFA and -0.159 [p < 0.01] for
      linoleic acid). CONCLUSIONS: The serum n-3 PUFA compositions were inversely
      related with the hs-CRP levels, similar associations were also observed in n-6
      PUFA compositions. Our results suggest that dietary PUFA intake was inversely
      associated with attenuated inflammation in healthy Japanese population.

PMID- 26193855
TI  - Evaluation of CONUT for Clinical Malnutrition Detection and Short-Term Prognostic
      Assessment in Hospitalized Elderly People.
AB  - OBJECTIVES: To assess agreement between the CONUT and Mini Nutritional Assessment
      (MNA) instruments in detecting malnutrition in hospitalized elderly patients and
      to determine their prognostic value compared to that of serum albumin alone in
      relation to in-hospital and 1-month and 6-month post-discharge mortality rates.
      DESIGN: Prospective observational study. SETTING: A Catalan regional hospital.
      PARTICIPANTS: 2155 patients admitted to an acute geriatric unit were assessed
      using MNA and CONUT and were followed up for 6 months after discharge.
      MEASUREMENTS: On admission, data were collected on age, sex, referral, geriatric
      syndromes, cognitive status, functional status and nutritional status according
      to MNA (as the gold standard). Plasma albumin, total cholesterol and lymphocyte
      levels were recorded to implement CONUT. Mortality was recorded until 6 months
      after discharge. RESULTS: Sample characteristics: 61.3% females, mean age 84.9
      years, mean Charlson index 2.2. CONUT sensitivity and specificity for
      malnutrition were 43% and 71.6%, respectively, with positive and negative
      predictive values of 88.9% and 19.2%. MNA, CONUT and albumin alone were good
      predictors of mortality but showed similar sensitivity and specificity results.
      CONCLUSION: CONUT agreement with MNA in nutritional risk assessments for elderly
      people is poor. Although CONUT is a good predictor of short-and medium-term
      mortality, it adds little to information provided by albumin alone.

PMID- 26193856
TI  - Knowledge and Attitudes of Nursing Staff Towards Malnutrition Care in Nursing
      Homes: A Multicentre Cross-Sectional Study.
AB  - BACKGROUND: The international literature shows that there are considerable
      deficits in nutritional care provision in nursing homes. Limited knowledge and
      negative attitudes can contribute to these deficits but international studies on
      knowledge and attitudes among nursing staff are rare. OBJECTIVE: The study aimed
      to assess the knowledge and attitudes of registered nurses and nurse aides
      towards malnutrition care in nursing homes. DESIGN: This study followed a
      multicentre, cross sectional design. SETTING AND PARTICIPANTS: The study was
      performed in 66 Austrian nursing homes with 1152 participants. MEASUREMENTS: The
      validated Knowledge of Malnutrition-Geriatric (KoM-G) questionnaire and the Staff
      Attitudes to Nutritional Nursing Care Geriatric (SANN-G) scale were used for data
      collection. RESULTS: On average, 60.6% of the respondents answered the questions
      correctly, whereas registered nurses knew significantly more (65.6%) than nurse
      aides (57.3%). The question that was answered correctly by most dealt with the
      factors that positively affect oral nutritional intake (87.2%) while the question
      which was incorrectly answered by most was on the professions involved in
      malnutrition treatment (26.1%). 39.2% of respondents had positive attitudes
      towards nutritional care. Registered nurses displayed more positive attitudes
      (48.1%) than nurse aides (33.6%). The most positive attitudes were shown in the
      'Intervention' subscale while the least positive attitudes were indicated in the
      'Norms' subscale. A medium positive correlation between knowledge and attitudes
      was found (r=.423, p<0.000). CONCLUSION: This study identified specific knowledge
      deficits and areas of negative attitudes in registered nurses and nurse aides,
      which will enable tailored training programmes to be developed.

PMID- 26193857
TI  - The Rapid Cognitive Screen (RCS): A Point-of-Care Screening for Dementia and Mild
      Cognitive Impairment.
AB  - OBJECTIVES: There is a need for a rapid screening test for mild cognitive
      impairment (MCI) and dementia to be used by primary care physicians. The Rapid
      Cognitive Screen (RCS) is a brief screening tool (< 3 min) for cognitive
      dysfunction. RCS includes 3-items from the Veterans Affairs Saint Louis
      University Mental Status (SLUMS) exam: recall, clock drawing, and insight. Study
      objectives were to: 1) examine the RCS sensitivity and specificity for MCI and
      dementia, 2) evaluate the RCS predictive validity for nursing home placement and
      mortality, and 3) compare the RCS to the clock drawing test (CDT) plus recall.
      METHODS: Patients were recruited from the St. Louis, MO Geriatric Research
      Education and Clinical Center (GRECC), Veterans Affairs Medical Center (VAMC)
      hospitals (study 1) or the Saint Louis University Geriatric Medicine and
      Psychiatry outpatient clinics (study 2). Study 1 participants (N=702; ages 65-92)
      completed cognitive evaluations and 76% (n=533/706) were followed up to 7.5 years
      for nursing home placement and mortality. Receiver operator characteristic (ROC)
      curves were computed to determine sensitivity and specificity for MCI (n=180) and
      dementia (n=82). Logistic regressions were computed for nursing home placement
      (n=31) and mortality (n=176). Study 2 participants (N=168; ages 60-90) completed
      the RCS and SLUMS exam. ROC curves were computed to determine sensitivity and
      specificity for MCI (n=61) and dementia (n=74). RESULTS: RCS predicted dementia
      and MCI in study 1 with optimal cutoff scores of <= 5 for dementia
      (sensitivity=0.89, specificity=0.94) and <= 7 for MCI (sensitivity=0.87,
      specificity=0.70). The CDT plus recall predicted dementia and MCI in study 1 with
      optimal cutoff scores of <= 2 for dementia (sensitivity=0.87, specificity=0.85)
      and <= 3 for MCI (sensitivity=0.62, specificity=0.62). Higher RCS scores were
      protective against nursing home placement and mortality. The RCS predicted
      dementia and MCI in study 2. CONCLUSIONS: The 3-item RCS exhibits good
      sensitivity and specificity for the detection of MCI and dementia, and higher
      cognitive function on the RCS is protective against nursing home placement and
      mortality. The RCS may be a useful screening instrument for the detection of
      cognitive dysfunction in the primary care setting.

PMID- 26193858
TI  - Effect of Vitamin Intake on Cognitive Decline in Older Adults: Evaluation of the
      Evidence.
AB  - OBJECTIVES: The objective of this review was to evaluate the evidence from human
      studies on the intake of vitamins, either as monotherapies or in combination with
      other vitamins, as neuroprotective agents that may delay the onset of cognitive
      decline in older adults. METHODS: Evidence-based methodologies were used to
      capture and evaluate the highest levels of evidence. FINDINGS: The current
      evidence available showed no association for cognitive benefits of vitamins B6 or
      B12 as a monotherapy, and recent systematic reviews provide no clear evidence
      that supplementation with vitamin B6, B12 and/or folic acid improves dementia
      outcomes or slows cognitive decline, even though it may normalise homocysteine
      levels. Meta-analyses from systematic reviews have shown an association between
      low vitamin D levels and diminished cognitive function, although causality cannot
      be confirmed from the available evidence. There is no convincing evidence for an
      association of vitamin A, vitamin C or vitamin E either as a monotherapy or in
      combination with other antioxidant vitamins such as beta-carotene and the
      prevention of cognitive decline. The appraisal of nineteen systematic reviews and
      meta-analyses has highlighted the heterogeneity between studies, and the need for
      better consensus on definitions of cognitive decline, duration of testing and
      agreement on which specific endpoints are clinically relevant. CONCLUSIONS:
      Evaluation of the totality of the currently available evidence indicates that
      intake of the above vitamins, either as a monotherapy, or in combination with
      other vitamins, has no clinically-relevant effect on delaying cognitive decline
      or delaying the onset of dementia in older adults.

PMID- 26193859
TI  - Predictivity of Early Depressive Symptoms for Post-Stroke Depression.
AB  - OBJECTIVES: Depression is a frequent complication after stroke. However, little
      is known about the predictive value of early self-reported depressive symptoms
      (DS) for later development of post-stroke depression (PSD) 6 months after
      discharge. DESIGN: Using a prospective longitudinal design, we investigated the
      prevalence of DS and examined their predictive value for depressive disorders 6
      months after stroke while statistically controlling major established PSD risk
      factors. SETTING AND PARTICIPANTS: During inpatient rehabilitation, 96 stroke
      patients were screened for DS. After 6 months, 71 patients were attainable for a
      follow-up. MEASUREMENTS: DS was assessed using the 15-item Geriatric Depression
      Scale (GDS-15). At follow-up a telephone interview that included the Structured
      Clinical Interview for Psychiatric Disorders (SCID), which is based on DSM-IV
      criteria, and the GDS-15 was conducted. Patients with major depression (MD) at
      the follow-up were considered to have PSD. RESULTS: Regression analyses were
      conducted to examine the influence of early DS on PSD after 6 months while
      controlling for age, premorbid depression, and functional and cognitive
      impairments. The percentage of patients who scored above the GDS-15 cut-off for
      clinically relevant DS increased significantly, from 37% to 44%, after 6 months.
      According to the SCID, 27% of stroke patients fulfilled the criteria for MD, and
      another 16% fulfilled those for minor depression. Logistic regression showed that
      DS at baseline significantly predicted PSD at follow-up (odds ratio: 1.43; 95%
      CI: 1.15-1.8). CONCLUSION: Self-reported DS during inpatient rehabilitation are
      predictive for PSD 6 months after discharge. Assessment of early DS contributes
      to identifying stroke patients at risk for PSD, thereby facilitating prevention
      and treatment.

PMID- 26193860
TI  - Wrist Actigraphy: A Simple Way to Record Motor Activity in Elderly Patients with
      Dementia and Apathy or Aberrant Motor Behavior.
AB  - INTRODUCTION: In dementia, behavioral psychological symptoms are frequent and
      variable. OBJECTIVE: To assess the value of wrist actigraphy as a measure of
      disorder in motor behavior especially apathy, aberrant motor behavior, agitation
      and anxiety. METHODS: Cross sectional observational study of consecutive patients
      older than 75 years admitted to an intermediate care unit of a geriatric hospital
      ward during a two-year period. Psycho behavioral symptoms and cognitive status
      were assessed using the NPI scale and MMSE and diagnosis of dementia was done
      using DSMIV criteria. A wrist actigraph was worn for 10 days to record motor
      activity, sleep time and number of periods of sleep. RESULTS: 183 patients were
      included. Among patients with dementia, a significant decrease in motor activity
      was recorded in those with apathy from 9h to 12h and 18h to 21h (p <0.05) and in
      those with anxiety from 21h to 24h (p <0.05). Aberrant motor behavior in dementia
      was associated with a significant increase in motor activity from 21h to 24h (p
      <0.01). Agitation was not associated with a significant differences in motor
      activity. CONCLUSIONS: Wrist actigraphy can be used to record motor activity in
      elderly patients with dementia especially in those with apathy and aberrant motor
      behavior.

PMID- 26193861
TI  - In Vivo Antioxidant Properties of Lotus Root and Cucumber: A Pilot Comparative
      Study in Aged Subjects.
AB  - OBJECTIVES: To compare the effects of lotus root and cucumber on antioxidant
      function in aged subjects. DESIGN: Pilot comparative study. SETTING: Research
      setting with vegetable intervention. PARTICIPANTS: Healthy aged subjects over the
      age of sixty. INTERVENTION: 30-day supplementation of lotus root or cucumber
      powder. MEASUREMENTS: Plasma value of ferric reducing antioxidant power assay,
      activity of antioxidant enzymes, contents of some antioxidants, oxidation
      products, hemolysis, blood mononuclear cell DNA damage and urinary excretion of 8
      hydroxy-2'-deoxyguanosine were measured before and after the intervention.
      RESULTS: Plasma glutathione peroxidase activity, contents of vitamin C, total
      phenolics were significantly increased, while plasma uric acid content
      significantly decreased in both groups at the end of the intervention. Meanwhile,
      hemolysis was significantly reduced in both groups and DNA injury rate of blood
      mononuclear cells in lotus root group and the ratio of comet tail length to total
      length in cucumber group were also declined significantly post-intervention.
      However, plasma value of ferric reducing antioxidant power assay, contents of
      reduced glutathione, vitamin E, malondialdehyde, oxidized low density
      lipoprotein, carbonyls and activity of superoxide dismutase and catalase were not
      changed significantly in both group after the intervention. CONCLUSION: These
      results suggest that lotus root and cucumber are not remarkably different in
      improving antioxidant function in aged subjects, though they are significantly
      different in antioxidant capacity in vitro. The benefits observed in this study
      may come from the additive or synergistic combinations of antioxidants contained
      in vegetables.

PMID- 26193862
TI  - Consumption of Branched-Chain Amino Acids Is Inversely Associated with Central
      Obesity and Cardiometabolic Features in a Population of Brazilian Middle-Aged
      Men: Potential Role of Leucine Intake.
AB  - OBJECTIVE: To assess the potential associations of branched-chain amino acids
      (BCAA) consumption with central obesity (CObesity) and cardiometabolic risk
      factors in a population of Brazilian middle-aged men. Special attention was given
      to leucine intake. DESIGN: Cross-sectional study. SETTING: Universidade Federal
      de Vicosa, Vicosa, Brazil. PARTICIPANTS: Two-hundred ninety-six middle-aged men
      (Age: 50.5 +/- 5.0 years; Body mass index: 25.8 +/- 3.5 kg/m2). MEASUREMENTS:
      Anthropometry, lifestyle features, blood biochemical parameters were assessed and
      dietary intake was estimated by a food frequency questionnaire. Participants were
      classified by the occurrence of CObesity, hypertriglyceridemia (HTG),
      hypertriglyceridemic waist phenotype (HWP) and metabolic syndrome (MetS).
      RESULTS: Subjects in the BCAA highest tertile (>=0.17 g/kg/d) presented lower
      occurrence of CObesity (36.0% vs 72.4%, P<0.01, z=-5.10), HTG (17.0% vs 30.6%
      P<0.032, z=-2.32), HWP (23.0% vs 46.9%, P<0.01, z=-3.57) and MetS (19.0% vs
      34.7%, P<0.01, z=-2.57). They also exhibited lower values for Castelli index
      (total cholesterol:HDL-c) and triglycerides: HDL-c ratio than those in the first
      tertile, regardless of interfering factors (i.e. habitual physical activity, work
      position, smoking habit, and energy intake). Interestingly, leucine consumption
      showed similar associations with cardiometabolic risk factors, as compared to
      BCAA consumption (P<0.05). CONCLUSION: BCAA consumption was cross-sectionally and
      negatively associated with relevant cardiometabolic risk factors in a population
      of Brazilian middle-aged men. The content of leucine in BCAA consumption may have
      contributed to such relationship.

PMID- 26193863
TI  - Physical Fitness, Activity and Hand-Grip Strength Are Not Associated with
      Arterial Stiffness in Older Individuals.
AB  - OBJECTIVES: Whereas evidence exists about the benefits of intensive exercise on
      cardiovascular outcomes in older adults, data are lacking regarding long-term
      effects of physical fitness and physical activity on cardiovascular health.
      Therefore, we aimed to investigate the longitudinal association of physical
      fitness, physical activity and muscle strength with arterial stiffness measures.
      DESIGN: a longitudinal follow-up study (2 years) of data from the B-PROOF study.
      SETTING: a subgroup of the B-PROOF study (n=497). PARTICIPANTS: Four hundred
      ninety-seven participants with a mean age of 72.1 years (SD 5.4) of which 57% was
      male. MEASUREMENTS: All performed at baseline and after two-year follow-up.
      Arterial stiffness was estimated by pulse wave velocity (PWV) measured with
      applanation tonometry. Furthermore, augmentation index (AIx) and aortic pulse
      pressure (PP) were assessed. Physical activity was estimated using a validated
      questionnaire regarding daily activities. Physical fitness was measured with a
      physical performance score, resulting from a walking, chair-stand and balance
      test. Muscle strength was assessed with hand-grip strength using a handheld
      dynamometer. RESULTS: The median performance score was 9.0 [IQR 8.0-11.0], the
      mean physical activity was 744.4 (SD 539.4) kcal/day and the mean hand-grip
      strength was 33.1 (SD 10.2) kg. AIx differed between the baseline and follow-up
      measurement (26.2% (SD 10.1) vs. 28.1% (SD 9.9); p < 0.01), whereas PWV and
      aortic PP did not. In multivariable linear regression analysis, physical
      performance, physical activity and hand-grip strength at baseline were not
      associated with the amount of arterial stiffness after two years of follow-up.
      CONCLUSION: Physical fitness, activity and muscle strength were not associated
      with arterial stiffness. More research is warranted to elucidate the long-term
      effects of daily and intensive physical activity on arterial stiffness in an
      elderly population.

PMID- 26193864
TI  - Obesity, Muscular Strength, Muscle Composition and Physical Performance in an
      Elderly Population.
AB  - OBJECTIVE: To evaluate the association between BMI levels, muscular strength,
      muscle composition and physical performance in the elderly. DESIGN: Italians
      subjects from the Progetto Veneto Anziani (ProVA) study were analyzed. SETTING:
      The ProVa was a population study focused on chronic diseases and functional
      limitations in Italian subjects aged >=65 years living in two Northeast Italian
      cities. PARTICIPANTS: The ProVa study included 3099 subjects. ProVa participants
      with unknown information on BMI or disability status were excluded. The final
      sample was thus represented by 1.188 men, and 1.723 women. MEASUREMENTS: Physical
      performance was measured with the Short Physical Performance Battery (SPPB) and
      leg muscular strength with dynamometry. Fat distribution and skeletal muscle
      composition were measured in an abdominal single-scan magnetic resonance (MRI) in
      a randomly selected sample of 348 subjects. Study population was stratified by
      BMI classes. RESULTS: An association between BMI levels and SPPB was observed.
      Normal weight subjects showed the best SPPB scores (8.29+/-0.03), with
      significant differences compared to underweight (7.50+/-0.15; p<0.001),
      overweight (8.12+/-0.02; p<0.001), class I (7.72+/-0.04; p<0.001), class II
      (6.67+/-0.09; p<0.001) and class III obesity (5.88+/-0.24; p<0.001). This pattern
      was not modified by adjustment for possible confounders. Compared to normal
      weight subjects (22.9+/-0.1 kg), leg muscular strength was higher in overweight
      (23.8+/-0.1; p<0.001) and in class I obesity (24.5+/-0.1; p<0.001), but it was
      reduced in class II (21.4+/-0.3; p<0.001) and class III (19.8+/-0.9; p<0.001).
      The association between BMI and impaired physical performance was not affected by
      adjustment for muscular strength. An inverse association between SPPB scores and
      fat infiltration in skeletal muscle was observed in patients with abdominal MRI.
      CONCLUSION: A poor physical performance was observed in overweight and obese
      elderly subjects. Leg strength was reduced only in subjects with severe obesity.
      Physical performance was negatively influenced by the degree of fat infiltration
      in skeletal muscle.

PMID- 26193865
TI  - C-Reactive Protein and Resistance Exercise in Community Dwelling Old Adults.
AB  - OBJECTIVES: C-reactive protein (CRP), an acute phase reactant, has been
      associated with atherosclerosis and has also been discussed as a target for
      intervention. The effects of resistance exercise on CRP are currently not clear.
      The present analysis investigated the response of CRP to resistance exercise in
      old adults. DESIGN: Intervention study. SETTING: Community. PARTICIPANTS: Old
      Icelandic adults (N = 235, 73.7 +/- 5.7 years, 58.2% female). INTERVENTION:
      Twelve-week resistance exercise program (3 times/week; 3 sets, 6-8 repetitions at
      75-80% of the 1-repetition maximum) designed to increase strength and muscle mass
      of major muscle groups. MEASUREMENTS: C-reactive protein (CRP). RESULTS: Mean CRP
      levels were 7.1 +/- 4.6 mg/dL at baseline, thirty-six (15.6%) subjects had
      abnormally high CRP (>10 mg/L) values at baseline. After the resistance exercise
      program the overall changes in CRP were minor and not significant. However, CRP
      decreased considerably in participants with high CRP at baseline (-4.28 +/- 9.41
      mg/L; P = 0.015) but increased slightly in participants with normal CRP (0.81 +/-
      4.58 mg/L, P = 0.021). CONCLUSIONS: Our study shows that the concentrations of
      circulating CRP decreased considerably after a 12-week resistance exercise
      program in participants with abnormally high CRP at baseline, possibly reducing
      thus risk for future disease. CRP changed little in participants with normal CRP
      at the start of the study.

PMID- 26193866
TI  - Isolation and characterization of mesenchymal stromal progenitors from the
      temporomandibular joint disc.
AB  - Disorders of the temporomandibular joint (TMJ) complex affect 6-12% of the
      population; the joint's disc is usually involved. Tissue engineering and
      regenerative medicine may constitute a promising therapeutic approach, with
      resident stromal progenitor cells a key factor in the process. We hypothesized
      that the TMJ disc (TMJD) contains multipotent stromal progenitors that may play
      an important role in regeneration of the disc. TMJD cells were cultured and
      evaluated for growth kinetics and colony-forming units (CFUs). Single cell
      derived clones were isolated and induced to differentiate toward the osteogenic,
      adipogenic and chondrogenic lineages by culturing in various induction media.
      Flow cytometry was used to identify multipotent stromal cell surface markers in
      additional cell samples, and reverse transcription-polymerase chain reaction (RT
      PCR) was used to determine gene expression patterns within isolated cells. High
      numbers of CFUs were observed, indicating cell self-renewal. Biochemical assays
      showed significantly higher alkaline phosphatase (ALP) activity, lipid droplet
      concentration and glycosaminoglycan levels in cells cultured in osteogenic,
      adipogenic and chondrogenic induction medium, respectively. Approximately 1% of
      the total cell population demonstrated the capability to differentiate into all
      three mesenchymal lineages. Chondrogenic gene levels within TMJD-derived cells
      were significantly reduced in passaged culture. Our results support the
      hypothesis that multipotent stromal progenitor cells populate the TMJD and
      possess proliferation and differentiation capabilities. These cells may
      contribute to the regeneration potential of dysfunctional tissue and become the
      primary component in future attempts at tissue engineering or regeneration of
      this complex. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26193867
TI  - Combination therapy: New hope for alcoholic hepatitis?
AB  - Alcoholic hepatitis (AH) is a severe form of alcoholic liver disease with high
      mortality. The pathogenesis of AH is not fully understood, but it is generally
      believed that inflammation is a key factor leading to liver failure in AH.
      Steroids, which have broad immunosuppressive effects, have been used for the
      treatment of AH over the last forty years. Steroids elicit modest improvement in
      short-term survival rate in patients with severe AH, but also cause severe side
      effects. Several specific inflammatory targets (e.g., IL-1, LPS, and gut
      microbiota) are currently under investigation for the treatment of AH with the
      goal to obviate or reduce steroid administration. In addition to inflammation,
      impaired liver regeneration is another major cause of liver failure in AH, which
      deteriorates further after steroid treatment because inflammation plays a key
      role in promoting liver repair. Interleukin-22 (IL-22) is a promising drug for
      the treatment of AH because of its hepatoprotective and anti-fibrotic functions
      and relatively few known side effects. In addition, IL-22 treatment also
      ameliorates bacterial infection and kidney injury, two major complications
      associated with severe AH. IL-22 is currently under investigation in preclinical
      and clinical studies and may hold great promise for AH by providing more
      beneficial effects and fewer side effects than current therapies. 

PMID- 26193868
TI  - Chronic alcohol drinking: Liver and pancreatic cancer?
AB  - Cancer is a multifactorial disease that results from complex interactions of
      numerous risk factors - genetic and environmental - over time, eventually leading
      to the diseased phenotypes. Thus, while epidemiological studies can point to risk
      factors, they cannot determine cause and effect relationships, and are unable to
      give biological and clinical insights into carcinogenesis. The link between any
      risk factor and carcinogenesis needs to be validated in experimental models. This
      is particularly true in epidemiological studies on alcohol consumption and its
      consequences. While there is no doubt that heavy alcohol consumption has
      devastating health effects, the inconsistencies in alcohol-related
      epidemiological studies and cancer suffer from possible sources of the
      variability in outcomes, ranging from inaccuracy of self-report of consumption to
      the problem of correlating cancer that started decades earlier to current or
      recent alcohol consumption. To further study the interactions between alcohol and
      cancer, the use of "Molecular Pathological Epidemiology" (MPE) advocated by Ogino
      et al. for dissecting the interplay between etiological factors, cellular and
      molecular characteristics, and disease progression in cancer is appropriate. MPE
      does not consider cancer as a single entity, rather it integrates analyses of
      epidemiological studies with the macroenvironment and molecular and
      microenvironment. This approach allows investigating the relationships between
      potential etiological agents and cancer based on molecular signatures. More
      research is needed to fully elucidate the link between heavy alcohol consumption
      and pancreatic cancer, and to further investigate the roles of acetaldehyde and
      FAEEs in pancreatic carcinogenesis.

PMID- 26193869
TI  - Management of alcohol recurrence before and after liver transplantation.
AB  - Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide
      and can lead to steatosis, steatohepatitis, fibrosis, cirrhosis and
      hepatocellular carcinoma. The primary effective treatment for patients with ALD
      is total alcohol abstinence, although sometimes impossible, liver transplant (LT)
      is the gold standard treatment for end-stage ALD, which represents the second
      most common diagnosis among patients undergoing this procedure. Liver transplant
      in ALD has better results than those for other etiologies. The alcohol
      consumption recidivism after LT is frequent and 10% to 15% of these resume heavy
      drinking with consequences to the new liver. The "6-month rule" of abstinence is
      an arbitrary threshold used in many transplant centers and has never been shown
      to affect survival after LT. The optimal abstinence period in pre-transplant
      remains unclear. The patients in the pre- and post-transplant period need
      evaluation of a multidisciplinary team, as psychiatrist, addiction specialists,
      including counselling and attendance to support groups. The impact of alcohol
      relapse on post-transplant outcomes is not entirely clear but is worse with
      continuing heavy drinking, with poorer survival beyond the fifth post-transplant
      year malignancy and cardiovascular disease and not recurrent liver failure. Acute
      alcoholic hepatitis, in careful selected cases, should be transplanted and have
      comparable survival outcomes. Prevention of alcoholic recidivism has proved to be
      the most important treatment after liver transplantation. 

PMID- 26193870
TI  - Proangiogenic factors in the development of HCC in alcoholic cirrhosis.
AB  - Alcoholic liver disease, the most common cause of liver cirrhosis, is associated
      with an increased risk for hepatocellular carcinoma. Angiogenic factors have been
      implicated in pathophysiology of cirrhosis, and of hepatocellular carcinoma, and
      in particular of alcoholic liver cirrhosis, due to alcohol induced hypoxia
      associated with increased hepatic oxygen consumption. In one study, it was found
      that among genetic polymorphisms in proangiogenic factors, KDR and VEFGA may
      confer an increased risk of HCC, in patients with ALD. There is need of further
      studies of the proangiogenic factors in HCC, in order to help us define their use
      as prognostic markers and also as markers of response to treatment.

PMID- 26193871
TI  - New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and
      Metastasis.
AB  - The medicinal use of aspirin stretches back to ancient times, before it was
      manufactured in its pure form in the late 19th century. Its accepted mechanistic
      target, cyclooxygenase (COX), was discovered in the 1970s and since this landmark
      discovery, the therapeutic application of aspirin and other non-steroidal anti
      inflammatory drugs (NSAIDs) has increased dramatically. The most significant
      benefits of NSAIDs are in conditions involving chronic inflammation (CI). Given
      the recognized role of CI in cancer development, the use of long-term NSAID
      treatment in the prevention of cancer is an enticing possibility. COX-2 is a key
      driver of CI, and here we review COX-2 expression as a predictor of survival in
      various cancer types, including breast. Obesity and post-partum involution are
      natural inflammatory states that are associated with increased breast cancer
      risk. We outline the COX-2 mediated mechanisms contributing to the growth of
      cancers. We dissect the cellular mechanism of epithelial-mesenchymal transition
      (EMT) and how COX-2 may induce this to facilitate tumor progression. Finally we
      examine the potential regulation of COX-2 by c-Myb, and the possible interplay
      between c-Myb/COX-2 in proliferation, and hypoxia inducible factor-1 alpha
      (HIF1alpha)/COX-2 in invasive pathways in breast cancer. 

PMID- 26193872
TI  - ERrrr...where are the progenitors? Hormone receptors and mammary cell
      heterogeneity.
AB  - The mammary epithelium is a highly heterogenous and dynamic tissue that includes
      a range of cell types with varying levels of proliferative capacity and
      differentiation potential, from stem to committed progenitor and mature cells.
      Generation of mature cells through expansion and specification of immature
      precursors is driven by hormonal and local stimuli. Intriguingly, although
      circulating hormones can be directly sensed only by a subset of mammary cells,
      they also regulate the behaviour of cells lacking their cognate receptors through
      paracrine mechanisms. Thus, mapping the hormonal signalling network on to the
      emerging mammary cell hierarchy appears to be a difficult task. Nevertheless, a
      first step towards a better understanding is the characterization of the hormone
      receptor expression pattern across individual cell types in the mammary
      epithelium. Here we review the most relevant findings on the cellular
      distribution of hormone receptors in the mammary gland, taking into account
      differences between mice and humans, the methods employed to assess receptor
      expression as well as the variety of approaches used to resolve the mammary cell
      heterogeneity. 

PMID- 26193873
TI  - X-linked protoporphyria: Iron supplementation improves protoporphyrin overload,
      liver damage and anaemia.

PMID- 26193875
TI  - Does the isolation effect require attention?
AB  - An item that differs from the surrounding items is remembered better than an item
      that is consistent with its surroundings; this is known as the von Restorff
      effect or isolation effect (von Restorff, Psychologische Forschung, 18, 299-342,
      1933). Theoretical explanations have proposed that the isolate is processed
      differently from control items, though some research has suggested that this
      processing might require more attention for semantic than for physical isolates.
      To test this possibility, in the present study we examined the isolation effects
      for physical isolates and semantic isolates under full and divided attention.
      Participants viewed lists of categorized words, with some lists containing either
      a physical or a semantic isolate, followed by immediate written free recall.
      Across three experiments, divided attention eliminated the semantic isolation
      effect but did not impact the physical isolation effect. Furthermore, semantic
      isolates were output earlier in recall than controls, whereas physical isolates
      were output more similarly to controls. These findings suggest that semantic
      isolation effects require attention during encoding, whereas physical isolation
      effects are relatively automatic. 

PMID- 26193876
TI  - Drug discovery approaches to irritable bowel syndrome.
AB  - INTRODUCTION: Irritable bowel syndrome (IBS) is defined by symptoms of abdominal
      pain and altered bowel habits without detectable organic disease. Antidepressants
      and serotonin receptor modulators are used to treat IBS, but rare serious adverse
      events highlight the safety hurdle. Newer drugs with secretory and motility
      effects via local gut mechanisms have been successfully approved for IBS, often
      by registering first in a related, non-IBS condition to optimize dosing,
      formulation and therapeutic window. AREAS COVERED: This review looks at
      approaches for novel IBS drug discovery. The underlying pathologies can be
      tackled locally from the 'outside-in' (intestinal lumen, mucosa and
      neuromuscular) to identify therapeutic targets. The article discusses the
      mechanisms associated with bile acid malabsorption, microbial dysbiosis,
      decreased intestinal barrier function, immune dysregulation, motility and
      visceral hypersensitivity. EXPERT OPINION: Challenges for new drug discovery are
      the unknown mechanisms underlying IBS, making it difficult to predict clinically
      efficacious molecular targets, limited options for translational research and
      disease progression biomarkers. Drugs acting locally via multiple targets (e.g.,
      eluxadoline [The U.S. Food and Drug Administration approved Viberzi (eluxadoline)
      for IBS-D on May 27th 2015], crofelemer) to validated mechanisms are proving
      successful with tolerable safety margins. Novel mechanisms, identified and
      optimized based on the emerging role of nutrient signaling, probiotics or
      microbial products, are promising. Therapeutic treatment earlier in disease
      progression may improve response and have longer term benefits.

PMID- 26193878
TI  - Egg cell-specific promoter-controlled CRISPR/Cas9 efficiently generates
      homozygous mutants for multiple target genes in Arabidopsis in a single
      generation.
AB  - Arabidopsis mutants produced by constitutive overexpression of the CRISPR/Cas9
      genome editing system are usually mosaics in the T1 generation. In this study, we
      used egg cell-specific promoters to drive the expression of Cas9 and obtained non
      mosaic T1 mutants for multiple target genes with high efficiency. Comparisons of
      12 combinations of eight promoters and two terminators found that the efficiency
      of the egg cell-specific promoter-controlled CRISPR/Cas9 system depended on the
      presence of a suitable terminator, and the composite promoter generated by fusing
      two egg cell-specific promoters resulted in much higher efficiency of mutation in
      the T1 generation compared with the single promoters. 

PMID- 26193879
TI  - Genotype-independent association between profound vitamin D deficiency and
      delayed sputum smear conversion in pulmonary tuberculosis.
AB  - BACKGROUND: Both vitamin D deficiency and genetic variants in the vitamin D
      receptor (VDR) have been reported to associate with delayed response to intensive
      phase therapy for pulmonary tuberculosis. Studies investigating the influence of
      genetic variants in vitamin D binding protein (DBP) and vitamin D 25-hydroxylase
      (CYP2R1) on vitamin D status and response to antituberculous therapy are lacking.
      METHODS: We conducted a longitudinal study in 260 patients initiating treatment
      for smear-positive pulmonary tuberculosis in Lahore, Pakistan. Vitamin D status
      and genotypes for polymorphisms in VDR (rs2228570, rs731236, rs1544410), DBP
      (rs7041, rs4588) and CYP2R1 (rs2060793, rs10500804, rs10766197) were determined
      at baseline. Sputum smear microscopy was performed at 2, 4, 6 and 8 weeks, and
      time to sputum smear conversion was estimated for each participant. Analyses were
      conducted to determine demographic, clinical and genetic determinants of baseline
      vitamin D status and time to sputum smear conversion. RESULTS: Profound vitamin D
      deficiency (serum 25[OH]D < 25 nmol/L) was highly prevalent at TB diagnosis
      (present in 54 % of patients), and was independently associated with female vs.
      male sex (adjusted OR 2.60, 95 % CI 1.50 to 4.52, P = 0.001), recruitment in
      October to March inclusive (adjusted OR 1.75, 95 % CI 1.00 to 3.04, P = 0.047)
      and bilateral vs. unilateral disease (adjusted OR 1.89, 95 % CI 1.49 to 4.52 P =
      0.025). Profound vitamin D deficiency was also independently associated with
      impaired response to antituberculous therapy (median time to sputum smear
      conversion 22.5 vs. 7.5 days for patients with serum 25[OH]D < 25 nmol/L vs. >=
      25 nmol/L, respectively; aHR 4.36, 95 % CI 3.25 to 6.65, P < 0.001). No
      polymorphisms in VDR, CYP2R1 and DBP studied associated with either baseline
      vitamin D status or time to sputum smear conversion. CONCLUSIONS: Profound
      vitamin D deficiency is very common among TB patients in Lahore, Pakistan, and is
      independently associated with significantly delayed sputum smear conversion.
      Polymorphisms in VDR, CYP2R1 and DBP did not associate with baseline vitamin D
      status or response to intensive-phase treatment in this patient group.

PMID- 26193880
TI  - First report of Edwardsiellosis in cage-cultured sharpsnout sea bream, Diplodus
      puntazzo from the Mediterranean.
AB  - BACKGROUND: Edwardsiella tarda, is a serious bacterial pathogen affecting a broad
      range of aquaculture fish species. The bacterium has also been reported as a
      human pathogen, however recent studies have dissociated the fish pathogenic
      Edwardsiella from those isolated from humans by placing them in a new species, E.
      piscicida. Here we report the first case of Edwardsiellosis in cultured
      sharpsnout sea breams, Diplodus puntazzo in Greece. CASE PRESENTATION: The
      disease has affected cultured sharpsnout sea breams of a commercial fish farm in
      a single location in East Greece. Two populations of sharpsnout sea breams
      stocked in two consecutive years in floating cages presented signs of disease
      which included nodules and abscesses in spleen and kidney, morbidity and
      cumulative mortality reaching 5.3 %. Using microbiological, biochemical and
      molecular tools we have identified Edwardsiella sp. as the main aetiological
      factor of the disease. Following phylogenetic analysis the bacterial isolates are
      grouped with the newly described Edwardsiella piscicida species. CONCLUSIONS:
      This is the first report of Edwardsiellosis in this species but most importantly
      in sea cage-cultured fish in the Mediterranean which may pose a serious threat
      for aquaculture fish species in this region.

PMID- 26193881
TI  - Eicosapentaenoic and docosahexaenoic acid-enriched high fat diet delays the
      development of fatty liver in mice.
AB  - BACKGROUND: Low hepatic content of n-3 PUFA has been associated with NAFLD in
      humans. Whether this is associated with reduced dietary intake or increased
      turnover of these FA is not clear. We have here investigated the effects of
      dietary fat quality on hepatic lipid storage and transcriptomics over time. AIM:
      To investigate the effects of quality of fat in a high fat diet (HFD) over time
      on hepatic lipid storage and liver transcriptomics. METHODS AND RESULTS: Male
      C57BL/6J mice were fed control, HFD-eicosapentaenoic acid (EPA)/ docosahexaenoic
      acid (DHA) or HFD-corn oil diet for 8 or 12 weeks. Body weight, body composition,
      plasma and hepatic triglyceride contents were measured. Hepatic transcriptomes
      were analysed by microarray followed by gene-set enrichment analyses. At 8 weeks,
      the HFD-corn oil mice had higher body weight and adipose depot mass than the HFD
      EPA/DHA but there were no differences at 12 weeks. Hepatic triglyceride content
      was lower in HFD-EPA/DHA fed compared with the HFD-corn oil fed mice at both time
      points. Enrichment analyses of the hepatic transcriptomes showed that lipid/fatty
      acid biosynthesis; transport and homeostasis were lower in the HFD-EPA/DHA fed
      compared with the HFD-corn oil fed mice. Genes encoding proteins associated to
      cytoplasmic lipid droplets were expressed at higher levels in livers from the HFD
      corn oil compared to HFD-EPA/DHA mice. CONCLUSIONS: Dietary EPA and DHA
      counteracted development of HFD-induced fatty liver. The liver transcriptome data
      implicate that the quality of dietary fat could modulate Ppar-related gene
      expression that in turn affects hepatic lipid storage and maintenance of
      metabolic health.

PMID- 26193882
TI  - Effects of the Swedish physical activity on prescription model on health-related
      quality of life in overweight older adults: a randomised controlled trial.
AB  - BACKGROUND: The effects of physical activity on prescription (PAP) on health
      related quality of life (HRQoL) in overweight adults are unclear. We therefore
      aimed to explore the effects of the Swedish PAP model on HRQoL in overweight
      older adults. METHODS: Participants were recruited from a cohort of men and women
      born between 1937 and 1938, and living in Stockholm County. Inclusion criteria
      were; insufficiently physically active, i.e. <30 min of at least moderate
      intensity physical activity (PA) per day; body mass index >25 kg/m(2); and waist
      circumference >=102 cm (men) or >=88 cm (women). Altogether, 101 individuals,
      aged 67 years, were randomly assigned to two parallel groups: intervention group
      (n = 47) receiving individualised PAP or control group (n = 54). The 36-item
      Short Form Health Survey (SF-36) was administered before and after the six months
      intervention. Main outcomes were the SF-36 physical component summary (PCS) and
      mental component summary (MCS) scores. Intention to treat analysis was utilised.
      Regression analysis was performed to assess whether changes in PA and body weight
      affected changes in HRQoL. RESULTS: At the six months follow-up, regarding the
      MCS score, the intervention group had improved significantly more (median: 4.4
      [interquartile range (IQR): -2.4 to 23.3]) vs (median: 0.0 [IQR: -4.0 to 4.9]); p
      < 0.05) and a higher proportion of participants had attained relevant
      improvements (OR 2.43 (95% CI 1.00-5.88) p < 0.05) compared to the controls. A
      within group improvement in the PCS score (median: 3.8 [IQR: -1.9 to 19.5] p <
      0.05) was found in the intervention group. Changes in PA and body weight had a
      small, but significant, mediating effect on the changes in HRQoL. CONCLUSIONS:
      PAP had a positive effect on HRQoL, measured by the SF-36 MCS, but no significant
      between group effect was seen on the PCS in overweight older adults. These
      effects were, to some extent, mediated by changes in PA and body weight. Our
      findings support clinical use of the Swedish PAP model. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02320760.

PMID- 26193883
TI  - beta-Catenin destruction complex-independent regulation of Hippo-YAP signaling by
      APC in intestinal tumorigenesis.
AB  - Mutations in Adenomatous polyposis coli (APC) underlie familial adenomatous
      polyposis (FAP), an inherited cancer syndrome characterized by the widespread
      development of colorectal polyps. APC is best known as a scaffold protein in the
      beta-catenin destruction complex, whose activity is antagonized by canonical Wnt
      signaling. Whether other effector pathways mediate APC's tumor suppressor
      function is less clear. Here we report that activation of YAP, the downstream
      effector of the Hippo signaling pathway, is a general hallmark of tubular
      adenomas from FAP patients. We show that APC functions as a scaffold protein that
      facilitates the Hippo kinase cascade by interacting with Sav1 and Lats1.
      Consistent with the molecular link between APC and the Hippo signaling pathway,
      genetic analysis reveals that YAP is absolutely required for the development of
      APC-deficient adenomas. These findings establish Hippo-YAP signaling as a
      critical effector pathway downstream from APC, independent from its involvement
      in the beta-catenin destruction complex. 

PMID- 26193884
TI  - The Negative Mode Proteome with Activated Ion Negative Electron Transfer
      Dissociation (AI-NETD).
AB  - The field of proteomics almost uniformly relies on peptide cation analysis,
      leading to an underrepresentation of acidic portions of proteomes, including
      relevant acidic posttranslational modifications. Despite the many benefits
      negative mode proteomics can offer, peptide anion analysis remains in its infancy
      due mainly to challenges with high-pH reversed-phase separations and a lack of
      robust fragmentation methods suitable for peptide anion characterization. Here,
      we report the first implementation of activated ion negative electron transfer
      dissociation (AI-NETD) on the chromatographic timescale, generating 7,601 unique
      peptide identifications from Saccharomyces cerevisiae in single-shot nLC-MS/MS
      analyses of tryptic peptides-a greater than 5-fold increase over previous results
      with NETD alone. These improvements translate to identification of 1,106
      proteins, making this work the first negative mode study to identify more than
      1,000 proteins in any system. We then compare the performance of AI-NETD for
      analysis of peptides generated by five proteases (trypsin, LysC, GluC,
      chymotrypsin, and AspN) for negative mode analyses, identifying as many as 5,356
      peptides (1,045 proteins) with LysC and 4,213 peptides (857 proteins) with GluC
      in yeast-characterizing 1,359 proteins in total. Finally, we present the first
      deep-sequencing approach for negative mode proteomics, leveraging offline low-pH
      reversed-phase fractionation prior to online high-pH separations and peptide
      fragmentation with AI-NETD. With this platform, we identified 3,467 proteins in
      yeast with trypsin alone and characterized a total of 3,730 proteins using
      multiple proteases, or nearly 83% of the expressed yeast proteome. This work
      represents the most extensive negative mode proteomics study to date,
      establishing AI-NETD as a robust tool for large-scale peptide anion
      characterization and making the negative mode approach a more viable platform for
      future proteomic studies. 

PMID- 26193885
TI  - Reply to the letter to the editor 'Ablative therapies for lung metastases: a need
      to acknowledge the efficacy and toxicity of stereotactic ablative body
      radiotherapy' by Siva et al.

PMID- 26193886
TI  - Insulin down-regulates the expression of ubiquitin E3 ligases partially by
      inhibiting the activity and expression of AMP-activated protein kinase in L6
      myotubes.
AB  - While insulin is an anabolic hormone, AMP-activated protein kinase (AMPK) is not
      only a key energy regulator, but it can also control substrate metabolism
      directly by inducing skeletal muscle protein degradation. The hypothesis of the
      present study was that insulin inhibits AMPK and thus down-regulates the
      expression of the ubiquitin E3 ligases, muscle atrophy F-box (MAFbx) and muscle
      RING finger 1 (MuRF1) in skeletal muscle cells. Differentiated L6 myotubes were
      treated with 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR)
      and/or compound C to stimulate and/or block AMPK respectively. These treatments
      were also conducted in the presence or absence of insulin and the cells were
      analysed by western blot and quantitative real-time PCR. In addition, nucleotide
      levels were determined using HPLC. The activation of AMPK with AICAR enhanced the
      mRNA levels of MAFbx and MuRF1. Insulin reduced the phosphorylation and activity
      AMPK, which was accompanied by reduced MAFbx and MuRF1 mRNA levels. Using a
      protein kinase B (PKB/Akt) inhibitor, we found that insulin regulates AMPK
      through the activation of Akt. Furthermore, insulin down-regulated AMPK alpha2
      mRNA. We conclude that insulin inhibits AMPK through Akt phosphorylation in L6
      myotubes, which may serve as a possible signalling pathway for the down
      regulation of protein degradation. In addition, decreased expression of AMPK
      alpha2 may partially participate in inhibiting the activity of AMPK.

PMID- 26193887
TI  - Serum adiponectin levels in patients with acute coronary syndromes: Serial
      changes and relation to infarct size.
AB  - BACKGROUND: The role of adiponectin in patients with acute coronary syndromes is
      incompletely defined. This study investigated adiponectin levels in patients with
      acute coronary syndromes and the association between adiponectin and 30-day
      infarct size and 1-year clinical outcomes. METHODS: Retrospective analysis of 120
      participants with acute coronary syndromes enrolled in the Immediate Myocardial
      Metabolic Enhancement During Initial Assessment and Treatment in Emergency care
      Trial. Blood levels were tested three times within 24 h of onset of ischaemic
      symptoms. Infarct size was measured at 30 days. The 1-year clinical outcome was
      the composite of all-cause mortality or hospitalization for heart failure.
      RESULTS: Using linear mixed models, log adiponectin levels decreased by -0.005
      ug/mL per hour (p = 0.035). After stratifying the analysis by gender, there was
      no decrease in log adiponectin in men; however, levels decreased by -0.01 ug/mL
      per hour in women (p = 0.02). Results of multivariable regression models showed
      no association between log adiponectin and infarct size (beta = -1.1, p = 0.64).
      Log adiponectin levels did not predict 1-year outcomes using Cox-proportional
      hazard models. CONCLUSION: There was a small decrease in plasma adiponectin
      shortly after symptoms of ischaemia, more noticeable in women. No relationship
      was found between adiponectin and infarct size or clinical outcomes. This adds to
      evidence showing no clear association between adiponectin and adverse outcomes in
      patients with acute coronary syndromes.

PMID- 26193888
TI  - Validation of markers with non-additive effects on milk yield and fertility in
      Holstein and Jersey cows.
AB  - BACKGROUND: It has been suggested that traits with low heritability, such as
      fertility, may have proportionately more genetic variation arising from non
      additive effects than traits with higher heritability, such as milk yield. Here,
      we performed a large genome scan with 408,255 single nucleotide polymorphism
      (SNP) markers to identify chromosomal regions associated with additive, dominance
      and epistatic (pairwise additive * additive) variability in milk yield and a
      measure of fertility, calving interval, using records from a population of 7,055
      Holstein cows. The results were subsequently validated in an independent set of
      3,795 Jerseys. RESULTS: We identified genomic regions with validated additive
      effects on milk yield on Bos taurus autosomes (BTA) 5, 14 and 20, whereas SNPs
      with suggestive additive effects on fertility were observed on BTA 5, 9, 11, 18,
      22, 27, 29 and the X chromosome. We also confirmed genome regions with suggestive
      dominance effects for milk yield (BTA 2, 3, 5, 26 and 27) and for fertility (BTA
      1, 2, 3, 7, 23, 25 and 28). A number of significant epistatic effects for milk
      yield on BTA 14 were found across breeds. However on close inspection, these were
      likely to be associated with the mutation in the diacylglycerol O-acyltransferase
      1 (DGAT1) gene, given that the associations were no longer significant when the
      additive effect of the DGAT1 mutation was included in the epistatic model.
      CONCLUSIONS: In general, we observed a low statistical power (high false
      discovery rates and small number of significant SNPs) for non-additive genetic
      effects compared with additive effects for both traits which could be an artefact
      of higher dependence on linkage disequilibrium between markers and causative
      mutations or smaller size of non-additive effects relative to additive effects.
      The results of our study suggest that individual non-additive effects make a
      small contribution to the genetic variation of milk yield and fertility. Although
      we found no individual mutation with large dominance effect for both traits under
      investigation, a contribution to genetic variance is still possible from a large
      number of small dominance effects, so methods that simultaneously incorporate
      genotypes across all loci are suggested to test the variance explained by
      dominance gene actions.

PMID- 26193889
TI  - What Brings You Here? Exploring Why Young Adults Seek Help for Social Anxiety.
AB  - Social anxiety disorder typically manifests in young adulthood, but there is an
      absence of qualitative research on the actual experiences of young adults
      suffering with this disorder. The aim of the present study was to investigate the
      lived experiences of 29 Norwegian university students who were seeking
      professional help for symptoms of social anxiety. We conducted in-depth
      interviews prior to a clinical trial. The interviews were transcribed and
      analyzed using a team-based thematic analysis method based on a hermeneutic
      phenomenological epistemology. We identified five themes: (a) from being shy to
      interpreting anxiety as a mental health problem, (b) experiencing emotions as
      threatening and uncontrollable, (c) encountering loneliness as relationships fall
      away, (d) hiding the vulnerable self from others, and (e) deciding to face social
      fears in the future. We relate our findings to existing theory and research,
      discuss our process of reflexivity, highlight study limitations, and suggest
      implications for future research. 

PMID- 26193890
TI  - Vibrational Properties of the Phosphate Group Investigated by Molecular Dynamics
      and Density Functional Theory.
AB  - The phosphate group (PO2(-)) is an important building block occurring in many
      components of living matter including nucleic acids. It provides distinct
      features in vibrational spectra and is useful as a local probe of NA conformation
      and interactions with the environment. For this purpose, it is desirable to
      explore in detail various factors influencing spectral shapes of characteristic
      phosphate vibrations. In the present study, effects of the solvent and
      conformational averaging are analyzed for simple model molecules,
      dimethylphosphate, ethylmethylphosphate, and ethylmethylthiophosphate. Infrared
      absorption (IR) and Raman spectra were measured and calculated using a
      combination of molecular dynamics (MD) and density functional theory (DFT). To
      fully understand the link between the structure and the spectra, the solvent has
      to be explicitly included in the computational modeling. The results indicate
      that vibrational properties of the phosphate moiety are very sensitive to its
      conformation and interactions with the aqueous environment indeed. Polarizable
      continuum solvent models without explicit water molecules provided significantly
      worse agreement with the experiment. The combined MD/DFT approach captures well
      spectral characteristics for the model systems and constitutes the most reliable
      basis for exploration of phosphate vibrational properties in biomolecular
      structural studies. 

PMID- 26193891
TI  - Low-dose growth hormone supplementation increases clinical pregnancy rate in poor
      responders undergoing in vitro fertilisation.
AB  - Poor ovarian response (POR) often means low success rates after in vitro
      fertilisation (IVF). We aim to study the impact of a low-dose growth hormone (GH)
      supplementation in pregnancy rates in poor responders in a prospective, self
      controlled study of 64 poor responders to previous IVF cycles, who failed to
      achieve pregnancy and were supplemented with low-doses of GH in a subsequent
      cycle using the same gonadotropin dose and protocol. Our primary endpoint was the
      clinical pregnancy rate (CPR), considering secondary endpoints, the number of
      retrieved oocytes, embryos, embryo quality and the proportion of cycles with
      embryo transfer. CPR in the GH group was 34.4%. Significant differences were
      observed for the GH group both in the number of top quality embryos (0.64 +/-
      0.88 versus 1.03 +/- 1.17, p < 0.05) and cryopreserved embryos (0.3 +/- 0.81
      versus 0.85 +/- 1.49, p < 0.05). This is, to our knowledge, the first clinical
      trial to use a low dose of GH as a supplement for IVF in POR patients. Despite
      this low dose, we achieved excellent success rates in patients with a very poor
      prognosis, at a reasonable cost and without side effects, which makes this a safe
      and cost-effective alternative. 

PMID- 26193892
TI  - Effects of hyperprolactinemia on the tibial epiphyseal plate of mice treated with
      sex hormones.
AB  - The aim of this study was to evaluate the effects of metoclopramide-induced
      hyperprolactinemia on the tibial epiphyseal plate of hormone-treated
      oophorectomized mice. For this purpose, 18 animals with intact ovaries were
      allocated to two groups, M (metoclopramide) and V (vehicle). One hundred and
      eight oophorectomized animals were allocated to 12 subgroups: Oophx/V (vehicle);
      Ooph/M (metoclopramide); Oophx/V + E (vehicle + estradiol); Oophx/M + E
      (metoclopramide + estradiol); Oophx/V + P (vehicle + progesterone); Oophx/M + P
      (metoclopramide + progesterone); Oophx/V + T (vehicle + testosterone); Oophx/M +
      T (metoclopramide + testosterone); Oophx/V + E + P (Vehicle + estradiol +
      progesterone); Oophx/M + E + P (metoclopramide + estradiol + progesterone);
      Oophx/V + E + P + T (vehicle + estradiol + progesterone + testosterone); Oophx/M
      + E + P + T (metoclopramide + estradiol + progesterone + testosterone). After a
      50-day treatment was performed histomorphometric and immunohistochemical cell
      death analysis. In the epiphyseal plate of the hyperprolactinemic and/or
      oophorectomized animals, cell proliferation and bone formation decreased,
      inducing intensified cell death. In the sex steroid-treated animals, estrogen
      boosted cell proliferation; progesterone, bone formation and testosterone, both
      cell proliferation and bone formation. These findings suggest that oophorectomy
      and hyperprolactinemia changed epiphyseal plate morphology causing cartilage
      degeneration. Treatment with combined sex steroids may diminish such deleterious
      effects.

PMID- 26193893
TI  - The Relationship Between a Person's Criminal History, Immediate Situational
      Factors, and Lethal Versus Non-Lethal Events.
AB  - When investigating serious violence, studies tend to look primarily at offenders
      and their background. This study investigates the influence of offenders' and
      victims' criminal history and immediate situational factors on the likelihood
      that violent events will end lethally. For this purpose, we compare lethal with
      non-lethal events, and combine Dutch criminal records with data from court files
      of those involved in lethal (i.e., homicide, n = 126) versus non-lethal events
      (i.e., attempted homicide, n = 141). Results reveal that both criminal history
      and immediate situational factors clearly matter for the outcome of violent
      events; however, immediate situational factors have the strongest effect on
      violent outcomes.

PMID- 26193894
TI  - Open-Source Data and the Study of Homicide.
AB  - To date, no discussion has taken place in the social sciences as to the
      appropriateness of using open-source data to augment, or replace, official data
      sources in homicide research. The purpose of this article is to examine whether
      open-source data have the potential to be used as a valid and reliable data
      source in testing theory and studying homicide. Official and open-source homicide
      data were collected as a case study in a single jurisdiction over a 1-year
      period. The data sets were compared to determine whether open-sources could
      recreate the population of homicides and variable responses collected in official
      data. Open-source data were able to replicate the population of homicides
      identified in the official data. Also, for every variable measured, the open
      sources captured as much, or more, of the information presented in the official
      data. Also, variables not available in official data, but potentially useful for
      testing theory, were identified in open-sources. The results of the case study
      show that open-source data are potentially as effective as official data in
      identifying individual- and situational-level characteristics, provide access to
      variables not found in official homicide data, and offer geographic data that can
      be used to link macro-level characteristics to homicide events.

PMID- 26193895
TI  - Muscle mass, structural and functional investigations of senescence-accelerated
      mouse P8 (SAMP8).
AB  - Sarcopenia is an age-related systemic syndrome with progressive deterioration in
      skeletal muscle functions and loss in mass. Although the senescence-accelerated
      mouse P8 (SAMP8) was reported valid for muscular ageing research, there was no
      report on the details such as sarcopenia onset time. Therefore, this study was to
      investigate the change of muscle mass, structure and functions during the
      development of sarcopenia. Besides the average life span, muscle mass, structural
      and functional measurements were also studied. Male SAMP8 animals were examined
      at month 6, 7, 8, 9, and 10, in which the right gastrocnemius was isolated and
      tested for ex vivo contractile properties and fatigability while the
      contralateral one was harvested for muscle fiber cross-sectional area (FCSA) and
      typing assessments. Results showed that the peak of muscle mass appeared at month
      7 and the onset of contractility decline was observed from month 8. Compared with
      month 8, most of the functional parameters at month 10 decreased significantly.
      Structurally, muscle fiber type IIA made up the largest proportion of the
      gastrocnemius, and the fiber size was found to peak at month 8. Based on the
      altered muscle mass, structural and functional outcomes, it was concluded that
      the onset of sarcopenia in SAMP8 animals was at month 8. SAMP8 animals at month 8
      should be at pre-sarcopenia stage while month 10 at sarcopenia stage. It is
      confirmed that SAMP8 mouse can be used in sarcopenia research with established
      time line in this study. 

PMID- 26193896
TI  - Elevated Hepatic miR-22-3p Expression Impairs Gluconeogenesis by Silencing the
      Wnt-Responsive Transcription Factor Tcf7.
AB  - Levels of miR-22-3p, a highly abundant hepatic microRNA, are abnormally increased
      in mouse models of insulin resistance and type 2 diabetes, yet its contribution
      to deregulated hepatic metabolism under diseased states is not well understood.
      Here, we unravel a novel link between elevated hepatic miR-22-3p expression and
      impaired gluconeogenesis in diabetic db/db mice via the regulation of Tcf7
      (transcription factor 7). Our data demonstrate that miR-22-3p binds to the 3'
      untranslated region of TCF7 and downregulates it, and this microRNA-mediated
      regulation of TCF7 increases the expression of enzymes of the gluconeogenic
      pathway in HepG2 cells. Small interfering RNA-mediated knockdown of TCF7 in HepG2
      cells also causes similar upregulation of gluconeogenic genes. Furthermore, in
      vivo silencing of miR-22-3p by antagomiR administration lowered random as well as
      fasting glucose levels in diabetic mice. miR-22-3p antagonism improved glucose
      tolerance and insulin sensitivity. Importantly, the hepatic Tcf7 levels were
      restored along with reduced hepatic glucose output, which was also reflected by
      the decreased expression of gluconeogenic genes. Our results support a critical
      role for miR-22-3p and its target, Tcf7, in the pathogenesis of diabetes by
      upregulating gluconeogenesis. Moreover, targeting the miR-22/Tcf7/Wnt axis might
      hold therapeutic potential for the treatment of altered hepatic physiology during
      insulin resistance and type 2 diabetes. 

PMID- 26193897
TI  - Local perceptions of causes of death in rural South Africa: a comparison of
      perceived and verbal autopsy causes of death.
AB  - BACKGROUND: Understanding how lay people perceive the causes of mortality and
      their associated risk factors is important for public health. In resource-limited
      settings, where verbal autopsy (VA) is used as the most expedient method of
      determining cause of death, it is important to understand how pre-existing
      concepts of cause of death among VA-informants may influence their VA-responses
      and the consequential impact on cause of death assessment. This study describes
      the agreement between VA-derived causes of death and informant-perceived causes
      and associated influential factors, which also reflects lay health literacy in
      this setting. METHOD: Using 20 years of VA data (n=11,228) from the Agincourt
      Health and Demographic Surveillance System (HDSS) site in rural South Africa, we
      explored the agreement between the causes of death perceived by the VA-informants
      and those assigned by the automated Inter-VA tool. Kappa statistics and
      concordance correlation coefficients were applied to measure agreement at
      individual and population levels, respectively. Multivariable regression models
      were used to explore factors associated with recognised lay perceptions of causes
      of mortality. RESULTS: Agreement between informant-perceived and VA-derived
      causes of death at the individual level was limited, but varied substantially by
      cause of death. However, agreement at the population level, comparing cause
      specific mortality fractions was higher, with the notable exception of
      bewitchment as a cause. More recent deaths, those in adults aged 15-49 years,
      deaths outside the home, and those associated with external causes showed higher
      concordance with InterVA. CONCLUSION: Overall, informant perception of causes of
      death was limited, but depended on informant characteristics and causes of death,
      and to some extent involved non-biomedical constructs. Understanding discordance
      between perceived and recognised causes of death is important for public health
      planning; low community understanding of causes of death may be detrimental to
      public health. These findings also illustrate the importance of using rigorous
      and standardised VA methods rather than relying on informants' reported causes of
      death.

PMID- 26193898
TI  - Quality of life among immigrants in Swedish immigration detention centres: a
      cross-sectional questionnaire study.
AB  - BACKGROUND: Detention of immigrants negatively affects their health and well
      being. Quality of life (QOL) is a broad concept incorporating the self-evaluation
      of one's own health and well-being that can provide an understanding of the
      health and well-being of immigrant detainees. The aim of this study was to
      estimate QOL among immigrant detainees in Sweden and to assess its relationship
      with the services provided in detention centres and with the duration of
      detention. DESIGN: All immigrants in all five existing Swedish detention centres
      (N=193) were invited to participate in the study (n=127). In this cross-sectional
      study, QOL was measured using the WHOQOL-BREF questionnaire, which was
      administered by the first author. The questionnaire contained four additional
      questions measuring participants' satisfaction with the services provided in
      detention. Associations between QOL domain scores and service satisfaction scores
      were assessed using regression analysis. The Spearman's rank correlation
      coefficient was calculated to measure the degree of association between the
      duration of detention and QOL scores. RESULTS: The mean QOL domain scores (out of
      100) were 47.0, 57.5, 41.9, and 60.5 for the environmental, physical,
      psychological, and social domains, respectively. The level of support detainees
      received from detention staff was significantly positively associated with
      detainees' physical (betaadjusted 3.93, confidence interval [CI] 0.06-7.80) and
      psychological (betaadjusted 5.72, CI 1.77-9.66) domain scores. There was also
      significant positive association between detainees' satisfaction with the care
      they received from detention staff and the domain scores. The general health
      score in the WHOQOL-BREF was significantly associated with the detainees' ability
      to understand the Swedish or English languages. Although not statistically
      significant, a longer duration of detention was negatively correlated with QOL
      scores. CONCLUSION: Immigrant detainees report low QOL. Services provided at the
      centres, especially the support received from detention staff, is positively
      associated with their QOL. A review of detention guidelines addressing language
      barriers, staff training, and duration of detention is highly recommended.

PMID- 26193899
TI  - Assessment of intravascular granulomas in testicular seminomas and their
      association with tumour relapse and dissemination.
AB  - AIMS: First, to determine the frequency of intravascular granulomas (IVGs) in
      seminomas and assess for the presence of entrapped seminoma cells. Second, to
      identify the relationship of this unusual form of vascular space invasion with
      tumour relapse and/or dissemination. METHODS: 86 cases of seminoma were reviewed
      to identify IVGs. Immunostaining for OCT3/4 and CD68 was performed. Pathological
      stage, presence of conventional vascular and rete testis invasion, parenchymal
      granulomas and follow-up were recorded. Multivariable analysis incorporating
      tumour size, vascular invasion (conventional granulomas and IVGs) and rete testis
      invasion was performed. RESULTS: IVGs were identified in 13 cases (13/86). CD68
      confirmed histiocytes in all cases. OCT3/4 identified tumour cells in 9/13
      seminomas. 27 patients had disease progression with either dissemination at
      presentation (n=11) or relapse (n=16). Of these 27 patients, 8 had IVG (29.6%).
      By comparison, 6 of 57 clinical stage 1 seminomas that did not relapse had IVG
      (10.53%). Multivariable analysis revealed that no single parameter was
      statistically significant at predicting tumour relapse and/or dissemination
      (size: HR 1.65; CI 0.71 to 3.82, p=0.24, rete testis invasion: HR 1.04; CI 0.48
      to 2.26, p=0.92, lymphovascular space invasion/IVG: HR 1.62; CI 0.65 to 4.01,
      p=0.30). CONCLUSIONS: IVGs may represent a previously unrecognised form of
      vascular space invasion in seminomas. Studies on larger cohorts are needed to
      demonstrate its clinical value.

PMID- 26193900
TI  - EBV-related primary splenic lymphocyte-depleted classical Hodgkin lymphoma.
AB  - Lymphocyte-depleted classical Hodgkin lymphoma (LDCHL) is the rarest entity among
      the classical Hodgkin lymphoma (CHL) subtypes, accounting for <1% of CHL cases in
      Western countries. Similarly, primary splenic Hodgkin lymphoma is a rare
      diagnosis among all cases of lymphomatous involvement of spleen. Representing a
      combination of these two rare entities is the primary splenic LDCHL, with only
      one case reported in the literature. Here, we report second case of primary
      splenic LDCHL with a unique presentation. The patient was a 60-year-old Caucasian
      HIV-negative woman with a history of extranodal pleuropulmonary marginal zone
      lymphoma (MZL) treated with rituximab who presented with new-onset splenomegaly.
      Splenectomy revealed large number of Hodgkin/Reed-Sternberg cells (CD15+, CD30+,
      PAX5+ and EBER+) with the background consisting of histiocytes and smaller number
      of lymphocytes and eosinophils. There was no evidence of nodal or other
      extranodal site involvement. Thus, in addition to being a very rare entity, this
      case also provides an additional point of interest: the disease arose in the
      backdrop of previous diagnosis of extranodal pleuropulmonary MZL successfully
      treated with rituximab. We discuss the potential implications. 

PMID- 26193901
TI  - Eosinophil chimerism in the differential diagnosis between DEK-NUP214-positive
      acute myeloid leukaemia relapse and chronic graft-versus-host disease.

PMID- 26193903
TI  - Tree holes as larval habitats for Aedes aegypti in urban, suburban and forest
      habitats in a dengue affected area.
AB  - Aedes aegypti (L.) (Diptera: Culicidae), the main vector of dengue and urban
      yellow fever in the world, is highly adapted to the human environment. Artificial
      containers are the most common larval habitat for the species, but it may develop
      in tree holes and other phytotelmata. This study assessed whether tree holes in
      San Ramon de la Nueva Oran, a city located in subtropical montane moist forest
      where dengue outbreaks occur, are relevant as larval habitat for Ae. aegypti and
      if the species may be found in natural areas far from human habitations. Water
      holding tree holes were sampled during 3 years once a month along the rainy
      season using a siphon bottle, in urban and suburban sites within the city and in
      adjacent forested areas. Larvae and pupae were collected and the presence and
      volume of water in each tree hole were recorded. Finding Ae. aegypti in forested
      areas was an isolated event; however, the species was frequently collected from
      tree holes throughout the city and along the sampling period. Moreover, larvae
      were collected in considerably high numbers, stressing the importance of taking
      into account these natural cavities as potential reinfestation foci within dengue
      control framework. 

PMID- 26193904
TI  - The Second Lebanon War Experience at Western Galilee Hospital.
AB  - The summer of 2006 in northern Israel served as the battleground for the second
      war against Hezbollah based along Israel's border with southern Lebanon. Western
      Galilee Hospital (WGH), which is located only 6 miles from the Lebanese border,
      served as a major medical center in the vicinity of the fighting. The hospital
      was directly impacted by Hezbollah with a Katyusha rocket, which struck the
      ophthalmology department on the 4th floor. WGH was able to utilize a 450-bed
      underground facility that maintained full hospital functionality throughout the
      conflict. In a major feat of rapid evacuation, the entire hospital population was
      relocated under the cover of darkness to these bunkers in just over 1 hour, thus
      emptying the building prior to the missile impact. Over half of the patients
      presenting during the conflict did not incur physical injury but qualified as
      acute stress disorder patients. The particulars of this evacuation remain unique
      owing to the extraordinary circumstances, but many of the principles employed in
      this maneuver may serve as a template for other hospitals requiring emergency
      evacuation. Hospital functionality drastically changed to accommodate the
      operational reality of war, and many of these tactics warrant closer
      investigation for possible implementation in other conflict zones.

PMID- 26193905
TI  - The extrusion of root canal cement containing paraformaldehyde into the inferior
      alveolar nerve canal resulting in infection and numbness.
AB  - AIM: To describe the impact of extruded paraformaldehyde-containing root canal
      cement into the inferior alveolar nerve canal following a delay in removal and
      the subsequent management of the case. SUMMARY: A 30-year-old man was referred
      for management of prolonged anaesthesia in the right mandibular region following
      root canal treatment. Panoramic and cone beam computed tomography findings
      revealed that overextruded root canal cement had penetrated into the inferior
      alveolar nerve canal beyond the distal root of the mandibular right second molar
      (tooth 47). The root canal cement contained paraformaldehyde. Initially, the
      patient refused surgical removal of the cement. However, after 3.5 months, the
      patient returned with an acute infection in the same region. After resolution of
      the acute abscess and root canal retreatment, surgical treatment was performed
      under general anaesthesia. Granulation tissue and necrotic bone were found
      associated with the cement.

PMID- 26193902
TI  - Evolutionary determinants of cancer.
AB  - Our understanding of cancer is being transformed by exploring clonal diversity,
      drug resistance, and causation within an evolutionary framework. The therapeutic
      resilience of advanced cancer is a consequence of its character as a complex,
      dynamic, and adaptive ecosystem engendering robustness, underpinned by genetic
      diversity and epigenetic plasticity. The risk of mutation-driven escape by self
      renewing cells is intrinsic to multicellularity but is countered by multiple
      restraints, facilitating increasing complexity and longevity of species. But our
      own species has disrupted this historical narrative by rapidly escalating
      intrinsic risk. Evolutionary principles illuminate these challenges and provide
      new avenues to explore for more effective control. SIGNIFICANCE: Lifetime risk of
      cancer now approximates to 50% in Western societies. And, despite many advances,
      the outcome for patients with disseminated disease remains poor, with drug
      resistance the norm. An evolutionary perspective may provide a clearer
      understanding of how cancer clones develop robustness and why, for us as a
      species, risk is now off the scale. And, perhaps, of what we might best do to
      achieve more effective control.

PMID- 26193906
TI  - Non-equivalent roles of two periplasmic subunits in the function and assembly of
      triclosan pump TriABC from Pseudomonas aeruginosa.
AB  - In Gram-negative bacteria, multidrug efflux transporters function in complexes
      with periplasmic membrane fusion proteins (MFPs) that enable antibiotic efflux
      across the outer membrane. In this study, we analyzed the function, composition
      and assembly of the triclosan efflux transporter TriABC-OpmH from Pseudomonas
      aeruginosa. We report that this transporter possesses a surprising substrate
      specificity that encompasses not only triclosan but the detergent SDS, which are
      often used together in antibacterial soaps. These two compounds interact
      antagonistically in a TriABC-dependent manner and negate antibacterial properties
      of each other. Unlike other efflux pumps that rely on a single MFP for their
      activities, two different MFPs, TriA and TriB, are required for triclosan/SDS
      resistance mediated by TriABC-OpmH. We found that analogous mutations in the
      alpha-helical hairpin and membrane proximal domains of TriA and TriB
      differentially affect triclosan efflux and assembly of the complex. Furthermore,
      our results show that TriA and TriB function as a dimer, in which TriA is
      primarily responsible for stabilizing interactions with the outer membrane
      channel, whereas TriB is important for the stimulation of the transporter. We
      conclude that MFPs are engaged into complexes as asymmetric dimers, in which each
      protomer plays a specific role.

PMID- 26193907
TI  - Effectiveness of a partnership-based self-management programme for patients with
      mild and moderate chronic obstructive pulmonary disease: a pragmatic randomized
      controlled trial.
AB  - AIMS: To evaluate the effectiveness of a 6-month, partnership-based self
      management programme for patients with mild and moderate chronic obstructive
      pulmonary disease. BACKGROUND: Self-management is a widely valued concept used to
      address contemporary issues of chronic health problems. Findings of self
      management programmes for people with chronic obstructive pulmonary disease are
      inconclusive. DESIGN: Pragmatic randomized control trial. METHODS: Patients, 45
      65 years old, with mild and moderate chronic obstructive pulmonary disease were
      invited with a family member. Experimental group (n = 48) participated in a 6
      month, partnership-based self-management programme consisting of: (a) three to
      four conversations between nurse and patient-family member; (b) 6 months of
      smoking cessation; and (c) interdisciplinary team-patient-family member group
      meeting. Control group (n = 52) received usual care. Data were collected at
      months zero, six and 12. The trial lasted from June 2009-March 2013. RESULTS:
      Patients with mild and moderate chronic obstructive pulmonary disease who
      participated in the partnership-based self-management programme perceived less
      intrusiveness of the disease and its treatment than patients in the control
      group. Patients in the experimental group did not have better health-related
      quality of life, less anxiety or depression, increased physical activity, fewer
      exacerbations or better smoking status than patients in the control group.
      Patients in both groups found participation in the research useful and important.
      CONCLUSION: The partnership-based self-management programme had benefits
      concerning perception of the intrusiveness of chronic obstructive pulmonary
      disease and its treatment on lifestyles, activities and interests for young
      patients with the disease in its early stages. High satisfaction in control
      group, low family attendance and the relatively short treatment period may
      explain the less than expected benefits of the programme.

PMID- 26193908
TI  - Looking Back to the Future: Current Issues Facing Nursing Education From the
      Reflections of a Member of the Silent Generation.
AB  - PROBLEM: As a member of the Silent Generation, the author, through her lived
      experiences, reflects upon the successes and challenges facing nursing education
      in the mid-20th to 21st centuries. METHOD: The author looks "back to the future"
      and reviews current issues that surround four key nursing education milestones.
      FINDINGS: From the early entry-level baccalaureate programs in the 1950s to the
      current growth of the Doctor of Nursing Practice as entry into advanced practice,
      milestones in nursing education are linked to the cultural changes and healthcare
      system demands that took place at the time and their influence on nursing
      education and the profession. CONCLUSION: Looking to the future, the author
      speaks of the implications from the forecasted changes in the healthcare system
      that will demand interdisciplinary education and practice and the continued need
      for nursing research to increase the body of scientific knowledge in practice,
      education, and technology. Keating.

PMID- 26193909
TI  - Distribution of Hypertrophy and Late Gadolinium Enhancement in Children and
      Adolescents with Hypertrophic Cardiomyopathy.
AB  - BACKGROUND: While well characterized in adult patients, the pattern of
      hypertrophy and the extent of myocardial scarring in hypertrophic cardiomyopathy
      (HCM) are insufficiently known. The aim of this study was to assess the
      hypertrophy patterns and the prevalence and clinical significance of scars in the
      hearts of young patients with HCM. METHODS AND RESULTS: A retrospective analysis
      of the imaging findings of 38 children (aged 12.83 +/- 2 years, 30 males) with
      HCM who underwent cardiac magnetic resonance imaging (CMR) was performed. In
      addition to left ventricular mass and volumes, the examinations were assessed for
      the pattern of hypertrophy and presence of late gadolinium enhancement (LGE). A
      myocardial signal intensity >=6 standard deviations above the mean of normal
      myocardium defined positive LGE. Left ventricular mass index averaged 110 +/- 34
      g/m(2) . Nineteen children (50%) had diffuse septal, 13 (34%) diffuse concentric
      and 6 (16%) isolated basal hypertrophy. Seven children (18%) had LGE. Patients
      with LGE had a greater left ventricular mass index than those without (136 +/- 34
      g/m(2) vs. 104 +/- 31 g/m(2) , P = .025). The only two patients who presented
      with an episode of aborted sudden cardiac death had LGE (P = .03). CONCLUSIONS:
      The most common hypertrophy pattern in children with HCM was diffuse septal
      hypertrophy. The incidence of LGE observed is lower than that reported in adults.
      The presence of LGE appears to confer a risk for adverse events.

PMID- 26193910
TI  - Reduced thalamocortical functional connectivity in temporal lobe epilepsy.
AB  - OBJECTIVE: In temporal lobe epilepsy (TLE), the thalamus is well known for its
      role in the propagation and spread of epileptiform activity. However, the
      integrity of thalamocortical functional connectivity (FC) in TLE and its relation
      to specific seizure patterns have not yet been determined. We address these
      issues with resting-state functional magnetic resonance imaging (fMRI). METHODS:
      Resting-state fMRI was performed on two groups of unilateral TLE patients: those
      with focal seizures only (16 left TLE, 16 right TLE) and those with additional
      generalized seizures (16 left TLE, 10 right TLE), and 16 matched controls. A
      thalamic parcellation based on FC between five nonoverlapping cortical seeds
      (prefrontal, motor, somatosensory, parietal-occipital, and temporal) and the
      ipsilateral thalamus was carried out to parcel each thalamus into five
      corresponding segments. FCs between each segment and its ipsilateral cortical
      seed were extracted and compared across groups using analyses of variance
      (ANOVAs). RESULTS: Compared to healthy controls, patients with TLE displayed
      decreased thalamocortical FC in multiple posterior and ventromedial thalamic
      segments of both the ictal and nonictal hemispheres. Our parcellation analysis
      revealed that these thalamic regions were functionally connected to the
      parietal/occipital and temporal lobes. In patients with TLE with focal seizures
      these regional thalamocortical FC decreases were limited to the ictal hemisphere.
      In contrast, TLE patients with both focal and generalized epileptiform activity
      displayed FC decreases in both the ictal and nonictal thalamus involving the
      dorsolateral pulvinar, a region preferentially connected to the parietal and
      occipital lobes. SIGNIFICANCE: Our data provide the first evidence of regional
      specific thalamocortical FC decreases in patients with unilateral TLE.
      Furthermore, our results demonstrate that patients with different seizure types
      present different thalamoparietal/occipital FC decrease patterns. While patients
      with focal seizures present thalamocortical FC decreases in the ictal hemisphere
      only, patients with additional generalized seizure activity also show
      thalamocortical FC decreases involving the thalamus in the nonictal hemisphere.

PMID- 26193911
TI  - Merging multiple longitudinal studies with study-specific missing covariates: A
      joint estimating function approach.
AB  - Merging multiple datasets collected from studies with identical or similar
      scientific objectives is often undertaken in practice to increase statistical
      power. This article concerns the development of an effective statistical method
      that enables to merge multiple longitudinal datasets subject to various
      heterogeneous characteristics, such as different follow-up schedules and study
      specific missing covariates (e.g., covariates observed in some studies but
      missing in other studies). The presence of study-specific missing covariates
      presents great statistical methodology challenge in data merging and analysis. We
      propose a joint estimating function approach to addressing this challenge, in
      which a novel nonparametric estimating function constructed via splines-based
      sieve approximation is utilized to bridge estimating equations from studies with
      missing covariates to those with fully observed covariates. Under mild regularity
      conditions, we show that the proposed estimator is consistent and asymptotically
      normal. We evaluate finite-sample performances of the proposed method through
      simulation studies. In comparison to the conventional multiple imputation
      approach, our method exhibits smaller estimation bias. We provide an illustrative
      data analysis using longitudinal cohorts collected in Mexico City to assess the
      effect of lead exposures on children's somatic growth. 

PMID- 26193912
TI  - Autologous blood transfusion in dogs with thoracic or abdominal hemorrhage: 25
      cases (2007-2012).
AB  - OBJECTIVE: To describe the use and outcome following autologous blood transfusion
      (ABT) in dogs. DESIGN: Retrospective study (January 2007-July 2012). SETTING:
      Private veterinary referral center. ANIMALS: Twenty-five dogs that underwent ABT
      secondary to thoracic or abdominal hemorrhage. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: The hospital transaction database was searched using the
      keyword "autotransfusion" from January 2007 to July 2012. Data collected included
      signalment, body weight, etiology of hemorrhage, source and method of collection,
      volumes and method of ABT administration, use of anticoagulant, reported
      complications, and outcome. Twenty-five dogs were included for a total of 27
      ABTs. Causes of hemorrhage included vascular trauma (14/25 dogs, 56%), ruptured
      tumor (8/25, 32%), and coagulopathy attributed to brodifacoum toxicosis (3/25,
      12%). Autologous blood was collected from the abdominal (19/25, 76%), thoracic
      (5/25, 20%), or abdominal and thoracic cavities (1/25, 4%). Anticoagulant was
      added to the ABT blood in 13 of 25 (52%) cases. A median ABT volume of 29.3 mL/kg
      (range 2.9-406.9 mL/kg) was infused through either a 210 MUm blood administration
      filter (21/27, 78%) or an 18 MUm hemonate filter (6/27, 22%). Reported
      complications that may have been associated with ABT included hypocalcemia (4/17,
      24%), hemolyzed serum (5/19, 26%), and prolonged coagulation times (4/5, 80%).
      These complications were considered of minimal clinical significance. Additional
      blood products were administered in 17 of 25 (68%) dogs. Seventeen (68%) dogs
      survived to discharge. Cause of death in the remaining cases was euthanasia or
      cardiac arrest secondary to uncontrollable hemorrhage. CONCLUSIONS: ABT is an
      adjunct to volume replacement in dogs with thoracic or abdominal hemorrhage
      secondary to vascular trauma, ruptured tumor, or anticoagulant rodenticide
      toxicosis. ABT may be used as bridge to definitive hemorrhage control,
      particularly when other blood products are not available or affordable.
      Complications may include hypocalcemia, prolonged coagulation times, and
      hemolysis.

PMID- 26193913
TI  - Successful abdominal operation without replacement therapy in a patient with
      combined factor V (FV) and FVIII deficiency due to novel homozygous mutation in
      LMAN1.

PMID- 26193914
TI  - An innate immune system-mimicking, real-time biosensing of infectious bacteria.
AB  - An animal cell-based biosensor was investigated to monitor bacterial
      contamination in an unattended manner by mimicking the innate immune response.
      The cells (RAW 264.7 cell line) were first attached onto the solid surfaces of a
      96-well microtiter plate and co-incubated in the culture medium with a sample
      that might contain bacterial contaminants. As Toll-like receptors were present on
      the cell membrane surfaces, they acted as a sentinel by binding to pathogen
      associated molecular patterns (PAMPs) of any contaminant. Such biological
      recognition initiates signal transmission along various pathways to produce
      different proinflammatory mediators, one of which, tumor necrosis factor-alpha
      (TNF-alpha) was measured using an immunosensor. To demonstrate automated
      bacterium monitoring, a capture antibody specific for TNF-alpha was immobilized
      on an optical fiber sensor tip and then used to measure complex formation in a
      label-free sensor system (e.g., Octet Red). The sensor response time depended
      significantly on the degree of agitation of the culture medium, controlling the
      biological recognition and further autocrine/paracrine signaling by cytokines.
      The response, particularly under non-agitated conditions, was also influenced by
      the medium volume, revealing a local gradient change of the cytokine
      concentration and also acidity, caused by bacterial growth near the bottom
      surfaces. A biosensor system retaining 50 MUL medium and not employing agitation
      could be used for the early detection of bacterial contamination. This novel
      biosensing model was applied to the real-time monitoring of different bacteria,
      Shigella sonnei, Staphylococcus aureus, and Listeria monocytogenes. They (<100
      CFU mL(-1)) could be detected automatically within the working time. Such
      analysis was carried out without any manual handling regardless of the bacterial
      species, suggesting the concept of non-targeted bacterial real-time monitoring.
      This technique was further applied to real sample testing (e.g., with milk) to
      exemplify, for example, the food quality control process without using any
      additional sample pretreatment such as magnetic concentration. 

PMID- 26193915
TI  - Dual template effect of supercritical CO2 in ionic liquid to fabricate a highly
      mesoporous cobalt metal-organic framework.
AB  - A hierarchical meso- and microporous metal-organic framework (MOF) was facilely
      fabricated in an ionic liquid (IL)/supercritical CO2 (SC CO2)/surfactant emulsion
      system. Notably, CO2 exerts a dual effect during the synthesis; that is, CO2
      droplets act as a template for the cores of nanospheres while CO2-swollen
      micelles induce mesopores on nanospheres. 

PMID- 26193916
TI  - Two-dimensional ultrafast vibrational spectroscopy of azides in ionic liquids
      reveals solute-specific solvation.
AB  - The stereochemistry and the reaction rates of bimolecular nucleophilic
      substitution reactions involving azides in ionic liquids are governed by solute
      solvent interactions. Two-dimensional ultrafast vibrational spectroscopy (2D-IR)
      shows that the picosecond dynamics of inorganic azides are substantially slower
      than organic azides in a series of homologous imidazolium ionic liquids. In
      water, both organic and inorganic azides spectrally diffuse with a ~2 ps time
      constant. In the aprotic solvent tetrahydrofuran, both kinds of azides spectrally
      diffuse on a timescale >5 ps. In ionic liquids, like 1-butyl-3-methylimidazolium
      tetrafluoroborate ([BMIM][BF4]), organic azides spectrally diffuse with a 2-4 ps
      time constant, and inorganic azides spectrally diffuse with a >40 ps time
      constant. Such a striking difference suggests that neutral (organic) and charged
      (inorganic) azides are incorporated in the ionic liquids with different solvation
      structures. 

PMID- 26193917
TI  - Systemic and Intravitreal Delivery of Dendrimers to Activated
      Microglia/Macrophage in Ischemia/Reperfusion Mouse Retina.
AB  - PURPOSE: Microglial activation and associated neuroinflammation play a key role
      in the pathogenesis of many diseases of the retina, including viral infection,
      diabetes, and retinal degeneration. Strategies to target activated microglia and
      macrophages and attenuate inflammation may be valuable in treating these
      diseases. We seek to develop dendrimer-based formulations that target retinal
      microglia and macrophages in a pathology-dependent manner, and deliver drugs,
      either intravenously or intravitreally. METHODS: Retinal uptake of cyanine dye
      (Cy5)-conjugated dendrimer (D-Cy5) was assessed in normal and
      ischemia/reperfusion (I/R) mouse eyes. Microglia/macrophage uptake of the
      dendrimer was assessed with immunofluorescence using rabbit Iba-1 antibody with
      Cy3-tagged secondary antibody (microglia/macrophage). Uptake in retina and other
      organs was quantified using fluorescence spectroscopy. RESULTS: Clearance of D
      Cy5 from normal eyes was almost complete by 72 hours after intravitreal injection
      and 24 hours after intravenous delivery. In eyes with activated microglia after
      I/R injury, D-Cy5 was retained by activated microglia/macrophage (Iba1+ cells) up
      to 21 days after intravitreal and intravenous administration. In I/R eyes, the
      relative retention of intravitreal and intravenous D-Cy5 was comparable, if a 30
      fold higher intravenous dose was used. CONCLUSIONS: Intravitreal and systemic
      dendrimers target activated microglia and show qualitatively similar retinal
      biodistribution when administered by either route. Results provide proof-of
      concept insights for developing dendrimer drug formulations as treatment options
      for retinal diseases associated with microglia or macrophage activation such as
      age-related macular degeneration, diabetic retinopathy, and retinal
      degenerations.

PMID- 26193918
TI  - Lacrimal Gland Volume Changes in Unilateral Primary Acquired Nasolacrimal
      Obstruction.
AB  - PURPOSE: To investigate whether unilateral primary acquired nasolacrimal duct
      obstruction (PANDO) causes Schirmer score and lacrimal gland volume changes in
      the contralateral non-PANDO eye. METHODS: Sixteen unilateral female PANDO and 16
      female controls were enrolled in the study. Exclusion criteria were orbital
      trauma, inflammation, infection, tumor involvement or infiltrative diseases,
      history of ocular surgery, ocular surface disorder, systemic drug use that
      interferes with tear secretion, and chronic use of topical eye drops. Bilateral
      lacrimal gland volumes were measured in computed tomography (CT) images of the
      participants. A Schirmer test without anesthesia was also performed on each
      participant. RESULTS: As there was no significant difference between the right
      and left eye values for Schirmer and gland size (P > 0.05), both eyes of the
      control group were enrolled in the study. The groups were age matched and the
      mean lacrimal gland was 0.479 cm3 in the PANDO as well as the contralateral non
      PANDO side, which was statistically smaller compared to the control eyes (0.580
      cm3) (P = 0.04). The mean Schirmer scores in the same order were 18.5 +/- 7.1 mm,
      13.2 +/- 8.9 mm, and 21.3 +/- 10.5 mm, respectively. Non-PANDO side Schirmer
      scores were lower compared to the other two groups, but statistical significance
      was present for the control group (P = 0.04). CONCLUSIONS: Compared to the
      control group, lacrimal gland volumes were bilaterally smaller in unilateral
      PANDO patients. Schirmer scores were statistically lower in the contralateral non
      PANDO side compared to the controls.

PMID- 26193919
TI  - Normal Perceptual Sensitivity Arising From Weakly Reflective Cone Photoreceptors.
AB  - PURPOSE: To determine the light sensitivity of poorly reflective cones observed
      in retinas of normal subjects, and to establish a relationship between cone
      reflectivity and perceptual threshold. METHODS: Five subjects (four male, one
      female) with normal vision were imaged longitudinally (7-26 imaging sessions,
      representing 82-896 days) using adaptive optics scanning laser ophthalmoscopy
      (AOSLO) to monitor cone reflectance. Ten cones with unusually low reflectivity,
      as well as 10 normally reflective cones serving as controls, were targeted for
      perceptual testing. Cone-sized stimuli were delivered to the targeted cones and
      luminance increment thresholds were quantified. Thresholds were measured three to
      five times per session for each cone in the 10 pairs, all located 2.2 to 3.3
      degrees  from the center of gaze. RESULTS: Compared with other cones in the same
      retinal area, three of 10 monitored dark cones were persistently poorly
      reflective, while seven occasionally manifested normal reflectance. Tested
      psychophysically, all 10 dark cones had thresholds comparable with those from
      normally reflecting cones measured concurrently (P = 0.49). The variation
      observed in dark cone thresholds also matched the wide variation seen in a large
      population (n = 56 cone pairs, six subjects) of normal cones; in the latter, no
      correlation was found between cone reflectivity and threshold (P = 0.0502).
      CONCLUSIONS: Low cone reflectance cannot be used as a reliable indicator of cone
      sensitivity to light in normal retinas. To improve assessment of early retinal
      pathology, other diagnostic criteria should be employed along with imaging and
      cone-based microperimetry.

PMID- 26193920
TI  - A Novel Motion-on-Color Paradigm for Isolating Magnocellular Pathway Function in
      Preperimetric Glaucoma.
AB  - PURPOSE: This study investigated a novel motion-on-color paradigm to functionally
      isolate the magnocellular pathway and evaluate its diagnostic value in
      preperimetric glaucoma patients. METHODS: Thirty patients with preperimetric
      primary open-angle glaucoma and 30 controls participated in this study. They were
      tested in both the foveal and peripheral locations. Contrast sensitivity was
      assessed for the direction discrimination of a moving luminance-modulated grating
      presented on top of a red/green isoluminant grating. The moving test grating was
      designed to target the magnocellular pathway, while the background red/green
      isoluminant grating was designed to saturate the parvocellular pathway. The
      luminance-modulated grating was presented at spatial frequency of 0.5 cyc/deg,
      moving horizontally at four temporal frequencies (3 Hz, 8 Hz, 15 Hz, 25 Hz).
      Participants were asked to indicate the direction of motion for the luminance
      grating. As a comparison condition, frequency-doubling stimuli were also
      presented in the periphery and participants were asked to detect the occurrence
      of the frequency-doubled pattern. Two-way repeated-measures analysis of variance
      was performed with temporal frequency modulations as within-subject factor and
      group as between-subject factor, while contrast sensitivity was the dependent
      variable. Receiver operating characteristic (ROC) analysis was used to
      characterize diagnostic performance of the new procedure in comparison with the
      frequency-doubling tests for preperimetric glaucoma. RESULTS: The contrast
      sensitivity function in both the fovea and the periphery showed an inverted "V"
      shape with highest sensitivity in the intermediate temporal frequencies,
      consistent with physiological properties of the magnocellular pathway. At the
      fovea, compared to the control group, the sensitivity for the glaucoma patients
      was slightly but not significantly reduced (P > 0.05), and there was no
      significant interaction between groups and temporal frequency (P > 0.05). In the
      periphery, patients' sensitivity was significantly lower (P < 0.001) than that of
      normal participants, especially in high temporal frequencies, as supported by a
      statistically significant interaction between groups and temporal frequency (P <
      0.001). The areas under ROC curves (AUROC) obtained for the motion-on-color
      paradigm in the periphery were 0.957 (25 Hz), 0.870 (15 Hz), 0.758 (8 Hz), and
      0.561 (3 Hz) and were 0.761 for the traditional frequency-doubling test.
      CONCLUSIONS: The motion-on-color paradigm revealed a loss of contrast sensitivity
      in the peripheral visual field in preperimetric glaucoma. When applied with
      stimuli at high temporal frequency, the new paradigm had higher diagnostic
      sensitivity and specificity than the traditional frequency-doubling test. The
      findings also support the viewpoint that selective evaluation of magnocellular
      pathway function could facilitate the earlier detection of functional defects in
      glaucoma before visual field defects by standard perimetry.

PMID- 26193922
TI  - Establishment of a Cell Line From Conjunctival Squamous Cell Carcinoma: PeCa-UkHb
      01.
AB  - PURPOSE: Until now, no epithelial cell line from conjunctival squamous cell
      carcinoma (SCC), to our knowledge, has existed; therefore, the establishment of a
      model cell line would be a useful tool for further studies. In particular, the
      phenotypic and molecular characterization in comparison to other SCC cells is of
      high interest because this would enable the development of new treatment options
      for clinical application in ophthalmic oncology. METHODS: Epithelial cells were
      isolated from a bulbar conjunctiva SCC obtained from a 74-year-old male,
      harvested by stepwise trypsinization and named PeCa-UkHb-01. Cell doubling and
      the number of passages were determined. Short tandem repeats (STR) and karyotype
      analyses were performed. Semiquantitative real-time PCR and immunocytochemical
      fluorescence staining were carried out to detect tumor and epithelial cell
      markers. RESULTS: The cells had an epithelial and conjunctival phenotype. They
      grew above passage number 50 in a doubling time at approximately 34.5 hours.
      Short tandem repeat analyses confirmed the cell origin, although loss of
      heterozygosity occurred. Karyotype analyses revealed a heterogeneous composition
      of the cell culture and the karyogram itself showed aberrations and changes in
      the chromosome numbers. Real-time PCR and immunocytochemical fluorescence
      staining revealed the expression of the stem cell markers such as ABCG2, p63,
      OCT4, c-MYC, and SOX2 as well as the conjunctival cytokeratin K19. CONCLUSIONS:
      PeCa-UkHb-01 cells fulfill the criteria of a cell line. They display
      characteristics of ocular carcinoma cells and therefore the presented cell line
      might serve for further basic research in ophthalmic oncology.

PMID- 26193921
TI  - Dexamethasone Stiffens Trabecular Meshwork, Trabecular Meshwork Cells, and
      Matrix.
AB  - PURPOSE: Treatment with corticosteroids can result in ocular hypertension and may
      lead to the development of steroid-induced glaucoma. The extent to which
      biomechanical changes in trabecular meshwork (TM) cells and extracellular matrix
      (ECM) contribute toward this dysfunction is poorly understood. METHODS: Primary
      human TM (HTM) cells were cultured for either 3 days or 4 weeks in the presence
      or absence of dexamethasone (DEX), and cell mechanics, matrix mechanics and
      proteomics were determined, respectively. Adult rabbits were treated topically
      with either 0.1% DEX or vehicle over 3 weeks, and mechanics of the TM were
      determined. RESULTS: Treatment with DEX for 3 days resulted in a 2-fold increase
      in HTM cell stiffness, and this correlated with activation of extracellular
      signal-related kinase 1/2 (ERK1/2) and overexpression of alpha-smooth muscle
      actin (alphaSMA). Further, the matrix deposited by HTM cells chronically treated
      with DEX is approximately 4-fold stiffer, more organized, and has elevated
      expression of matrix proteins commonly implicated in glaucoma (decorin, myocilin,
      fibrillin, secreted frizzle-related protein [SFRP1], matrix-gla). Also, DEX
      treatment resulted in a 3.5-fold increase in stiffness of the rabbit TM.
      DISCUSSION: This integrated approach clearly demonstrates that DEX treatment
      increases TM cell stiffness concurrent with elevated alphaSMA expression and
      activation of the mitogen-activated protein kinase (MAPK) pathway, stiffens the
      ECM in vitro along with upregulation of Wnt antagonists and fibrotic markers
      embedded in a more organized matrix, and increases the stiffness of TM tissues in
      vivo. These results demonstrate glucocorticoid treatment can initiate the
      biophysical alteration associated with increased resistance to aqueous humor
      outflow and the resultant increase in IOP.

PMID- 26193923
TI  - Stereo Photo Measured ONH Shape Predicts Development of POAG in Subjects With
      Ocular Hypertension.
AB  - PURPOSE: To identify objective, quantitative optic nerve head (ONH) structural
      features and model the contributions of glaucoma. METHODS: Baseline stereoscopic
      optic disc images of 1635 glaucoma-free participants at risk for developing
      primary open-angle glaucoma (POAG) were collected as part of the Ocular
      Hypertension Treatment Study. A stereo correspondence algorithm designed for
      fundus images was applied to extract the three-dimensional (3D) information about
      the ONH. Principal component analysis was used to identify ONH 3D structural
      features and the contributions of demographic features, clinical variables, and
      disease were modeled using linear regression and linear component analysis. The
      computationally identified features were evaluated based on associations with
      glaucoma and ability to predict which participants would develop POAG. RESULTS:
      The computationally identified features were significantly associated with future
      POAG, POAG-related demographics (age, ethnicity), and clinical measurements
      (horizontal and vertical cup-to-disc ratio, central corneal thickness, and
      refraction). Models predicting future POAG development using the OHTS baseline
      data and STEP features achieved an AUC of 0.722 in cross-validation testing. This
      was a significant improvement over using only demographics (age, sex, and
      ethnicity), which had an AUC of 0.599. CONCLUSIONS: Methods for identifying
      objective, quantitative measurements of 3D ONH structure were developed using a
      large dataset. The identified features were significantly associated with POAG
      and POAG-related variables. Further, these features increased predictive model
      accuracy in predicting future POAG. The results indicate that the computationally
      identified features might be useful in POAG early screening programs or as
      endophenotypes to investigate POAG genetics.

PMID- 26193924
TI  - Effects of Different Levels of Refractive Blur on Nighttime Pedestrian
      Visibility.
AB  - PURPOSE: The aim of this study was to systematically investigate the effect of
      different levels of refractive blur and driver age on nighttime pedestrian
      recognition and determine whether clothing that has been shown to improve
      pedestrian conspicuity is robust to the effects of blur. METHODS: Nighttime
      pedestrian recognition was measured for 24 visually normal participants (12
      younger mean = 24.9 +/- 4.5 years and 12 older adults mean = 77.6 +/- 5.7 years)
      for three levels of binocular blur (+0.50 diopter [D], +1.00 D, +2.00 D) compared
      with baseline (optimal refractive correction). Pedestrians walked in place on a
      closed road circuit and wore one of three clothing conditions: everyday clothing,
      a retro-reflective vest, and retro-reflective tape positioned on the extremities
      in a configuration that conveyed biological motion (known as "biomotion"); the
      order of conditions was randomized among participants. Pedestrian recognition
      distances were recorded for each blur and pedestrian clothing combination while
      participants drove an instrumented vehicle around a closed road course. RESULTS:
      The recognition distances for pedestrians were significantly reduced (P < 0.05)
      by all levels of blur compared with baseline. Pedestrians wearing biomotion
      clothing were recognized at significantly longer distances than for the other
      clothing configurations in all blur conditions. However, these effects were
      smaller for the older adults, who had much shorter recognition distances for all
      conditions tested. CONCLUSIONS: In summary, even small amounts of blur had a
      significant detrimental effect on nighttime pedestrian recognition. Biomotion
      retro-reflective clothing was effective, even under moderately degraded
      visibility conditions, for both young and older drivers.

PMID- 26193925
TI  - Being Conspicuous at Night on a Blurred Road.

PMID- 26193926
TI  - Comparison of Retinal Nerve Fiber Layer Thinning and Retinal Ganglion Cell Loss
      After Optic Nerve Transection in Adult Albino Rats.
AB  - PURPOSE: We compared the time-course and magnitude of retinal nerve fiber layer
      (RNFL) thinning with that of retinal ganglion cell (RGC) loss after intraorbital
      optic nerve transection (IONT) in adult rats. METHODS: At 3, 7, 12, or 21 days,
      or 1, 2, or 4 months after ONT, the retinas were imaged with spectral-domain
      optical coherence tomography (SD-OCT) using the circular-peripapillary scan and
      volume scan raster pattern (61 horizontal sections equally spaced) both centered
      in the optic nerve. In all sections, the RNFL and retinal thickness were measured
      to obtain the total values of the peripapillary scan and the values of three
      concentric sectors (400, 1200, and 2400 MUm in diameter) from the volume scan.
      After SD-OCT, retinas were dissected and immunoreacted for Brn3a and
      neurofilaments (pNFH) to identify RGCs and their intraretinal axons,
      respectively. Total numbers of RGCs were quantified. RESULTS: Thinning of the
      RNFL was first observed at 12 days in peripapillary scan (10% decrease) and
      progressed up to 4 months (72% decrease). The volume scan showed transient RNFL
      swelling in central and medial sectors at 3, 7, and 12 days followed by
      progressive significant thinning first observed at 21 days (central sector, 30%;
      medial sector, 40%) and 12 days (peripheral sector, 15%), respectively. Following
      IONT, Brn3a+ RGCs decreased to approximately 80%, 52%, 17%, 9%, 5%, 3%, and 2% at
      3, 7, 12, 21 days, and at 1, 2, and 4 months, respectively. Retinal ganglion cell
      axon immunodetection decreased from 12 days onwards. CONCLUSIONS: After IONT, RGC
      death is more severe and precedes thinning of the RNFL.

PMID- 26193927
TI  - Control of the cavity size of flexible covalent cages by silver coordination to
      the peripheral binding sites.
AB  - The synthesis of covalent cages consisting of two porphyrins connected by four
      flexible spacers each incorporating two 1,2,3-triazolyl ligands is reported.
      Binding of four silver(I) to the peripheral ligands induces conformational
      changes in solution and locks the porphyrins in a face-to-face disposition.

PMID- 26193928
TI  - Enantioselective, Catalytic Trichloromethylation through Visible-Light-Activated
      Photoredox Catalysis with a Chiral Iridium Complex.
AB  - An enantioselective, catalytic trichloromethylation of 2-acyl imidazoles and 2
      acylpyridines is reported. Several products are formed with enantiomeric excess
      of >=99%. In this system, a chiral iridium complex serves a dual function, as a
      catalytically active chiral Lewis acid and simultaneously as a precursor for an
      in situ assembled visible-light-triggered photoredox catalyst. 

PMID- 26193930
TI  - Immunoglobulin G (IgG) to IgM ratio in secondary adult dengue infection using
      samples from early days of symptoms onset.
AB  - BACKGROUND: Dengue virus (DENV) infection is an emerging arboviral infection in
      tropical and sub-tropical countries in South-East Asia, the Western Pacific and
      South and Central America. Secondary DENV infection is the most widely accepted
      risk factor for the development of severe forms. Methods to discriminate primary
      and secondary DENV infection may be of great prognostic value. ELISA based
      detection of specific antibodies (IgG and IgM) to the four DENV serotypes is
      valuable for determination of primary or secondary infection. Several studies had
      been performed to discriminate primary and secondary DENV infection using the
      ratio of IgG and IgM at the various days of symptoms onset. The aim of this study
      is to determine the best cut-off point of IgG to IgM ratio is able to
      discriminating secondary from primary DENV infection in adult using samples from
      early days of symptoms onset. METHODS: This prospective cohort study on 48 adult
      patients with DENV infected patients on the period of August 2011-January 2012 in
      5 out-patient settings health facilities in Tangerang district, Banten province,
      Indonesia with chief complaint of fever less than 3 days. Datas were collected on
      the day the patients attended health facilities, consisted of demographic,
      clinical, laboratory, and serological data. Serological data from 48 serum sample
      from adult patients were evaluated using Focus Diagnostics Dengue Virus IgM and
      IgG Capture DxSelectTM ELISA Kits to determine IgG, IgM index values and SD
      Bioline Dengue DuoTM Rapid Tests to determine NS1, IgG, and IgM result. RESULTS:
      According to NS1, IgG and IgM results, 36 patients were classified as secondary
      infection, 12 were primary Infection. The mean (SD) of IgG/IgM ratios for
      secondary and primary infection were 3.28 (0.54) and 0.18 (0.11) consecutively.
      The IgG/IgM ratio of >= 1.14 confirmed secondary infection with sensitivity of
      80.56 %, specificity 91.67 %, accuracy level 83.33 %, and likely hood ratio of
      (LR) 9.67. CONCLUSION: The IgG/IgM ratio of >= 1.14 as the best cut off point to
      determine secondary DENV infection in early days of symptoms onset.

PMID- 26193931
TI  - Structural Bioinformatics Inspection of neXtProt PE5 Proteins in the Human
      Proteome.
AB  - One goal of the Human Proteome Project is to identify at least one protein
      product for each of the ~20,000 human protein-coding genes. As of October 2014,
      however, there are 3564 genes (18%) that have no or insufficient evidence of
      protein existence (PE), as curated by neXtProt; these comprise 2647 PE2-4 missing
      proteins and 616 PE5 dubious protein entries. We conducted a systematic
      examination of the 616 PE5 protein entries using cutting-edge protein structure
      and function modeling methods. Compared to a random sample of high-confidence PE1
      proteins, the putative PE5 proteins were found to be over-represented in the
      membrane and cell surface proteins and peptides fold families. Detailed
      functional analyses show that most PE5 proteins, if expressed, would belong to
      transporters and receptors localized in the plasma membrane compartment. The
      results suggest that experimental difficulty in identifying membrane-bound
      proteins and peptides could have precluded their detection in mass spectrometry
      and that special enrichment techniques with improved sensitivity for membrane
      proteins could be important for the characterization of the PE5 "dark matter" of
      the human proteome. Finally, we identify 66 high scoring PE5 protein entries and
      find that six of them were reported in recent mass spectrometry databases; an
      illustrative annotation of these six is provided. This work illustrates a new
      approach to examine the potential folding and function of the dubious proteins
      comprising PE5, which we will next apply to the far larger group of missing
      proteins comprising PE2-4.

PMID- 26193932
TI  - Task sharing within a managed clinical network to improve child health in Malawi.
AB  - BACKGROUND: Eighty per cent of Malawi's 8 million children live in rural areas,
      and there is an extensive tiered health system infrastructure from village health
      clinics to district hospitals which refers patients to one of the four central
      hospitals. The clinics and district hospitals are staffed by nurses, non
      physician clinicians and recently qualified doctors. There are 16 paediatric
      specialists working in two of the four central hospitals which serve the urban
      population as well as accepting referrals from district hospitals. In order to
      provide expert paediatric care as close to home as possible, we describe our plan
      to task share within a managed clinical network and our hypothesis that this will
      improve paediatric care and child health. PRESENTATION OF THE HYPOTHESIS: Managed
      clinical networks have been found to improve equity of care in rural districts
      and to ensure that the correct care is provided as close to home as possible. A
      network for paediatric care in Malawi with mentoring of non-physician clinicians
      based in a district hospital by paediatricians based at the central hospitals
      will establish and sustain clinical referral pathways in both directions.
      Ultimately, the plan envisages four managed paediatric clinical networks, each
      radiating from one of Malawi's four central hospitals and covering the entire
      country. This model of task sharing within four hub-and-spoke networks may
      facilitate wider dissemination of scarce expertise and improve child healthcare
      in Malawi close to the child's home. TESTING THE HYPOTHESIS: Funding has been
      secured to train sufficient personnel to staff all central and district hospitals
      in Malawi with teams of paediatric specialists in the central hospitals and
      specialist non-physician clinicians in each government district hospital. The
      hypothesis will be tested using a natural experiment model. Data routinely
      collected by the Ministry of Health will be corroborated at the district. This
      will include case fatality rates for common childhood illness, perinatal
      mortality and process indicators. Data from different districts will be compared
      at baseline and annually until 2020 as the specialists of both cadres take up
      posts. IMPLICATIONS OF THE HYPOTHESIS: If a managed clinical network improves
      child healthcare in Malawi, it may be a potential model for the other countries
      in sub-Saharan Africa with similar cadres in their healthcare system and face
      similar challenges in terms of scarcity of specialists.

PMID- 26193933
TI  - The gender gap in sickness absence from work and the influence of parental
      absence on offspring absence 15 years later: register-based cohort of Norwegians
      born in 1974-1976.
AB  - BACKGROUND: Women have shown consistently higher levels of sickness absence from
      work in comparison to men, but explanations for this gender gap have not been
      completely understood. Life-course studies suggest that health and health-related
      social benefits in adult age are influenced by early life experiences. We aimed
      to estimate intergenerational associations with a 15-year time gap between
      parents' and offspring sickness absences, pursuing the hypothesis that this
      parental influence would have a stronger impact for women than for men. METHODS:
      All persons born alive between 1974 and 1976 in Norway were followed up in
      several national registries. Employed persons considered to be at risk of
      sickness absence and also with parents at risk of sickness absence (n = 78,878)
      were followed in the calendar year of their 33(rd) birthday with respect to
      spells lasting >16 days. The probability of one or more spells during this year
      constituted the one-year risk under study. Additive risk differences in
      association with an exposure (parental sickness absence 15 years earlier) were
      estimated in a binomial regression analysis. The estimates were adjusted for
      parental socioeconomic factors. RESULTS: The 1-year sickness absence risk was
      higher for women (30.4%) than for men (12.3%). The crude risk differences between
      those exposed and those unexposed to parental sickness absence were similar in
      percentage points (PP) for women (3.8; 95% confidence interval (CI) 2.6 to 4.9)
      and men (3.8; 95% CI 2.9 to 4.6). The risk differences were moderately attenuated
      after adjustment for parental education and father's income to 3.4 PP (2.2 to
      4.5) for women and 2.8 PP (2.0 to 3.7) for men. Male absence was more strongly
      associated with the father's than with the mother's sickness absence, while
      associations for women were stronger for the same diagnostic groups as their
      parents. CONCLUSIONS: Parental sickness absence was moderately associated with
      sickness absence in the next generation. Bias from unmeasured confounders cannot
      be entirely dismissed. Contrary to our hypothesis, associations were not stronger
      for women than for men. If parental sickness absence has a long-term causal
      effect, preventive measures could have an impact over generations.

PMID- 26193934
TI  - Impact of genetic similarity on imputation accuracy.
AB  - BACKGROUND: Genotype imputation is a common technique in genetic research.
      Genetic similarity between target population and reference dataset is crucial for
      high-quality results. Although several reference panels are available, it is
      often not clear which is the most optimal for a particular target dataset to be
      imputed. Maximizing genetic similarity between study sample and intended
      reference panels may be the straight forward method for selecting the genetically
      best-matched reference. However, the impact of genetic similarity on imputation
      accuracy has not yet been studied in detail. RESULTS: We performed a simulation
      study in 20 ethnic groups obtained from POPRES. High-quality SNPs were masked and
      re-imputed with MaCH, MaCH-minimac and IMPUTE2 using four different HapMap
      reference panels (CEU, CHB-JPT, MEX and YRI). Imputation accuracy was assessed by
      different statistics. Genetic similarity between ethnic groups and reference
      populations were measured by F -statistics (F(ST)) originally proposed by Wright
      and G -statistics (G(ST)) introduced by Nei and others. To assess the predictive
      power of these measures regarding imputation accuracy, we analysed relations
      between them and corresponding imputation accuracy scores. We found that
      population genetic distances between homogeneous reference and target populations
      were strongly linearly correlated with resulting imputation accuracies
      irrespective of considered distance measure, imputation accuracy measure,
      missingness and imputation software used. Possible exception was African
      population. CONCLUSION: Usage of G(ST) or F(ST)-related measures for predicting
      the optimal reference panel for imputation frameworks relying on a specific
      reference is highly recommended. A cut-off of G(ST) < 0.01 is recommended to
      achieve good imputation results for high-frequency variants and small data sets.
      The linear relationship is less pronounced for low-frequency variants for which
      we also observed a dependence of imputation accuracy on the number of polymorphic
      sites in the reference. We also show that the software specific measures MaCH-Rsq
      and IMPUTE-info must be interpreted with caution if the genetic distance of
      target and reference population is high.

PMID- 26193935
TI  - Histone deacetylase inhibitors merged with protein tyrosine kinase inhibitors.
AB  - Histone deacetylases (HDACs) are a family of metal enzymes which mainly regulates
      the acetylation level of histone, together with histone acetyl transferases
      (HATs). Recently, because many HDAC inhibitors (HDACis) have entered clinical
      trials for both solid and liquid tumors, HDACs are recognized as one of the
      promising targets for cancer treatment. The current trend is that more and more
      HDAC inhibitors are used in combination with other antitumor agents in order to
      optimize their effect and toxicity. Protein tyrosine kinases (PTKs) which play
      important roles in cellular signal transduction pathways and regulate series of
      physiological and biochemical processes, are another family of hot antitumor
      targets. This brief review will mainly talk about several reported chimeric HDACs
      PTKs inhibitors. 

PMID- 26193936
TI  - Multidrug resistant tuberculosis treatment in India.
AB  - Multidrug-resistant tuberculosis (MDR-TB) is posing a major public health threat
      as well as a big challenge to global efforts of tuberculosis control. The
      management of MDR-TB patients is difficult, expensive, challenging and quite
      often leads to treatment failure. To avoid further transmission, a comprehensive
      approach for rapid detection, proper treatment and effective public health
      measures must be ensured. It must also be emphasized that even optimal treatment
      of MDR-TB will not alone curb the epidemic. Efforts must be focused on the
      effective use of first-line drugs in every new case so as to prevent the ultimate
      emergence of MDR-TB. 

PMID- 26193937
TI  - Efficiency of dinoprostone insert for cervical ripening and induction of labor in
      women of full-term pregnancy compared with dinoprostone gel: A meta-analysis.
AB  - The aim of this study is to evaluate the efficiency of dinoprostone insert,
      compared with dinoprostone gel, for cervical ripening and induction of labor in
      women at term. We searched electronic databases and bibliographies of relevant
      papers to identify randomized controlled trials (RCTs) reporting dinoprostone
      insert and gel used for cervical ripening and induction of labor. Fifteen RCTs
      involving 1779 women were included. Dinoprostone insert could greatly contribute
      to vaginal delivery (VD) within 24 h compared with dinoprostone gel (OR = 2.35,
      95% CI = 1.34, 4.13) and the researchers found obvious statistically significant
      difference (p = 0.003). Yet a meta-analysis of the rates of VD, artificial
      assisted vaginal delivery and caesarean section (CS) revealed no margin between
      dinoprostone insert and gel. Dinoprostone insert showed a distinct superiority in
      terms of VD within 24 h and had an advantage of a shorter hospital stay and less
      postpartum hemorrhage in contrast to gel. Even though the insert did not perform
      much better than gel in decreasing the rate of CS and increasing the rate of VD,
      yet the superior benefit of the vaginal insert compared to gel was still not
      difficult to observe. 

PMID- 26193938
TI  - Topical administration of tranexamic acid in total hip arthroplasty: A meta
      analysis of Randomized Controlled Trials.
AB  - Tranexamic acid (TXA) is an antifibrinolytic drug which has been widely used in
      many areas of surgery. The purpose of our meta-analysis was to review randomized
      controlled trials (RCT) of the effectiveness and safety of topical TXA treatment
      in reducing total blood loss and transfusion rate for patients undergoing primary
      total hip arthroplasty (THA). A literature search was undertaken. Five eligible
      reports match the inclusion and exclusion standard. The topical administration of
      TXA groups revealed lower total blood loss(mean difference - 347 ml, 95% CI, -
      411 to - 282 mL; p < 0.00001) and transfusion rate (OR, 0.23 (p < 0.00001; 95%
      CI, 0.14-0.38)) compared with control groups. Meanwhile there was no
      statistically significant difference in the risk of developing thromboembolic
      events (OR, 1.64 (95% CI, 0.39-6.97); p = 0.5). Topical administration of TXA
      could significantly reduce total blood loss and transfusion requirements in
      primary THA, without increased thromboembolic complications.

PMID- 26193939
TI  - Compounds in a particular production lot of tryptic soy broth inhibit
      Staphylococcus aureus cell growth.
AB  - Staphylococcus aureus Newman strain and several methicillin-resistant S. aureus
      (MRSA) clinical isolates were grown on agar plates prepared with conventional
      lots of tryptic soy broth (TSB). Cell growth of these strains was inhibited on
      agar plates containing TSB of a particular product lot (lot A), whereas the cell
      growth of S. aureus RN4220 strain and several other MRSA clinical isolates was
      not inhibited. The cell growth of a strain of S. epidermidis was also inhibited
      on agar plates containing TSB of lot A, whereas the cell growth of Bacillus
      subtilis, Lactococcus lactis, Klebsiella pneumonia, Salmonella enterica, Serratia
      marcescens, Pseudomonas aeruginosa, and Escherichia coli was not inhibited.
      Although cell growth of the Newman strain was inhibited on agar plates containing
      TSB of lot A that was autoclaved in stainless steel or glass containers, cell
      growth inhibition was not observed when the medium was autoclaved in
      polypropylene containers. Compounds that inhibited the cell growth of the Newman
      strain were extracted from a polypropylene tube that was preincubated with liquid
      medium prepared from TSB of lot A. These findings suggest that polypropylene
      binding compounds in TSB of lot A inhibited the cell growth of S. aureus Newman
      strain, some MRSA clinical isolates, and S. epidermidis. 

PMID- 26193940
TI  - Identification and methods for prevention of Enterococcus mundtii infection in
      silkworm larvae, Bombyx mori, reared on artificial diet.
AB  - Previously, it was reported that Enterococcus mundtii (E. mundtii) was associated
      with flacherie disease of silkworm larvae reared on artificial diet. In this
      study, we report that E. mundtii was isolated from diseased silkworm larvae, and
      validated as a pathogenic bacterium of the animal. When silkworm larva was
      infected with 1.04 * 106 colony-forming units of E. mundtii via oral
      administration of diet, half population died within six days, indicating that the
      bacterium is pathogenic to silkworm. Less severe infection was found to cause
      anorexia and hamper the development of larvae. This pathogen was found to
      proliferate in both time- and dose-dependent manner in the gastrointestinal tract
      of the animal. The bacterium was isolated from powder of artificial diet made
      from mulberry leaves, and from mulberry leaves growing at a field. Minimum
      inhibitory concentration determination revealed that this bacterium was
      susceptible to tested antibiotics. Vancomycin treatment of diet significantly
      decreased the number of E. mundtii in intestine of silkworm larvae infected with
      the bacteria, compared to control. Furthermore, autoclaving or gamma ray
      irradiation of diet was also effective for exclusion of E. mundtii from the diet
      without the loss of its nutrient capacities. These results suggest that mulberry
      leaves used in making artificial diet for silkworm larvae is one of the sources
      of E. mundtii infection; and that antibiotic treatment, autoclaving or gamma ray
      irradiation of artificial diet can exclude the bacteria.

PMID- 26193941
TI  - Differentially expressed proteins in fluconazole-susceptible and fluconazole
      resistant isolates of Candida glabrata.
AB  - The current study aimed to identify the differences presented in the proteome of
      fluconazole-susceptible isolates of Candida glabrata compared to those with
      fluconazole-resistant ones. Two-dimensional differential gel electrophoresis was
      applied to identify proteins that were differentially expressed in fluconazole
      susceptible and fluconazole-resistant isolates of C. glabrata. Eight proteins
      including aspartyl-tRNA synthetase, translation elongation factor 3, 3
      phosphoglycerate kinase, ribosomal protein L5, coproporphyrinogen III oxidase,
      pyruvate kinase, G-beta like protein, and F1F0-ATPase alpha subunit were found to
      be more abundantly represented, while four proteins including vitamin B12
      (cobalamin)-independent isozyme of methionine synthase, microtubule-associated
      protein, adenylosuccinate synthetase, and aldose reductase were found to be less
      abundantly represented in fluconazole-resistant strains versus those with
      fluconazole-susceptible ones. These differentially expressed proteins were
      primarily associated with energy metabolism, stress response, and macromolecule
      synthesis. Proteins associated with energy metabolism, stress response, and
      macromolecule synthesis may play a role in the development of fluconazole
      resistance in the clinical isolates of C. glabrata. Multiple different mechanisms
      are involved in the development of fluconazole resistance in C. glabrata. These
      findings provide a scientific basis for discovering new genes and mechanisms
      associated with fluconazole resistance in C. glabrata.

PMID- 26193942
TI  - Hispidin and related herbal compounds from Alpinia zerumbet inhibit both PAK1
      dependent melanogenesis in melanocytes and reactive oxygen species (ROS)
      production in adipocytes.
AB  - Recently several compounds from Okinawa plants including Alpinia zerumbet
      (alpinia) were shown to inhibit directly the oncogenic/ageing kinase PAK1 (p21
      activated kinase 1). Furthermore, it was recently revealed that both PAK1 and
      PAK4 (p21-activated kinase 4) are equally essential for the melanogenesis in
      melanoma cells. Thus, in this study, we tested if several alpinia compounds
      inhibit the melanogenesis in melanoma (B16F10) cells, as well as the PAK1
      dependent up-regulation of both reactive oxygen species (ROS) and nitric oxide
      (NO) in cultured adipocytes (3T3-L1) without any cytotoxicity. The effect of
      alpinia compounds on the melanogenesis was measured by both the melanin content
      and intracellular tyrosinase activity in melanoma cells treated with 3-isobutyl-1
      methylxanthine (IBMX), a melanogenesis stimulating hormone. We found that
      (1E,3E,5E)-6-methoxyhexa-1,3,5-trien-1-yl)-2,5-dihydrofuran (MTD), 5,6
      dehydrokawain (DK), labdadiene, hispidin and dihydro-5,6-dehydrokawain (DDK) at
      50 MUg/mL reduced the melanin content by 63-79%. The MTD, DK and hispidin, at 50
      MUg/mL, inhibited tyrosinase activity by 70-83% in melanoma cells. Among these
      compounds, labdadiene, MTD, (E)-2,2,3,3-Tetramethyl8-methylene-7-(oct-6-en-1
      yl)octahydro-1H-quinolizine (TMOQ) and hispidin strongly inhibited the ROS
      production. Hispidin, labdadiene and MTD at 20 MUg/mL inhibited NO production by
      over 70%. These findings altogether suggest that some of these alpinia compounds
      could be potentially useful for the prevention or treatment of hyperpigmentation
      and obesity. 

PMID- 26193943
TI  - Liposome encapsulated of temozolomide for the treatment of glioma tumor:
      preparation, characterization and evaluation.
AB  - Temozolomide plays a critical role in curing glioma at present. The purpose of
      this work was to develop a suitable drug delivery system which could prolong the
      half-life, improve the brain targeting, and reduce the systemic effect of the
      drug. Temozolomide-liposomes were formulated by the method of proliposomes. They
      were found to be relatively uniform in size of 156.70 +/- 11.40 nm with a narrow
      polydispersity index (PI) of 0.29 +/- 0.04. The average drug entrapment
      efficiency and loading capacity were 35.45 +/- 1.48% and 2.81 +/- 0.20%,
      respectively. The pH of temozolomide-liposomes was 6.46. In vitro release studies
      were conducted by a dynamic dialysis. The results showed that temozolomide
      released slowly from liposomes compared with the solution group. The release
      behavior of temozolomide-liposomes was in line with First-order kinetics and
      Weibull equation. The pharmacokinetics study was evaluated by pharmacokinetics
      parameters. The t(1/2beta) and MRT of temozolomide-liposomes were 3.57 times and
      1.27 times greater than that of temozolomide solution. The Cmax and AUC values of
      temozolomide-liposomes were 1.10 times and 1.55 times greater than that of
      temozolomide solution. The results of pharmacokinetics study showed temozolomide
      liposomes prolonged the in vivo circulation time and increased AUC. Furthermore,
      the biodistribution in mice showed that temozolomide-liposomes preferentially
      decreased the accumulation of temozolomide in heart and lung and increased the
      drug concentration in brain after i.v. injection, which implied that temozolomide
      liposomes improved the therapeutic effect in the brain and reduced the toxicity
      in lung and heart.

PMID- 26193944
TI  - Preparation and evaluation of gelling granules to improve oral administration.
AB  - We investigated the preparation of oral granules that are solid when stored and
      that will swell and gel via water absorption, to address problems experienced by
      patients when taking medication. Important physical properties of gelling
      granules include elasticity that is normally smooth, quick water absorption and
      swelling properties that allow easy swallowing. We selected gelatin (GEL),
      succinylated gelatin (SUC-GEL) and iota-carrageenan (CAR) as matrix polymers that
      can undergo gelation at room temperature or at cold temperatures. Saccharide and
      polyethylene glycol (PEG) were added to prepare the experimental granules. The
      best matrix gelling granule was SUC-GEL. When xylitol (XYL), sorbitol (SOR) and
      maltitol (MAL) were added, elasticity was improved, and PEG improved the
      granule's water absorption behavior, which is an important element involved in
      gelation. The best granules were prepared by selecting SUC-GEL as the matrix and
      adding a small amount of PEG and XYL in amounts equal to that of SUC-GEL. 

PMID- 26193945
TI  - Effect of rice variety on the physicochemical properties of the modified rice
      powders and their derived mucoadhesive gels.
AB  - In the present study; the glutinous Niaw Sanpatong (NSP) and Niaw Koko-6 (NKK),
      and the non-glutinous Jasmine (JM) and Saohai (SH) were chemically modified. The
      difference of these rice varieties on the physicochemical characteristics of the
      modified rice powders and the properties of the derived gels were evaluated. X
      ray diffractometer was used for crystalline structure investigation of the rice
      powders and gels. A parallel plate rheometer was used to measure the rheological
      property of the gels. It was found that the non-glutinous varieties produced gels
      with higher mucoadhesive properties than the glutinous rice. Rheological behavior
      of JM and SH gels was pseudoplastic without yield value whereas that of NSP and
      NKK gels was plastic with the yield values of 1077.4 +/- 185.9 and 536.1 +/- 45.8
      millipascals-second (mPas), respectively. These different properties are
      considered to be due to the amylose content in different rice variety. The
      results suggest that the non-glutinous rice varieties with high amylose content
      are the most suitable for preparing gels as local delivery systems via the
      mucosal membrane. 

PMID- 26193946
TI  - Generic Selection Criteria for Safety and Patient Benefit [IV] - Physicochemical
      and pharmaceutical properties of brand-name and generic ketoprofen tapes.
AB  - The physicochemical and pharmaceutical properties (pH, peel force, water-vapor
      permeability, and stretchability) of brand-name and generic ketoprofen products
      were evaluated and compared. The pHs of Mohrus as a brand-name product and
      Teikoku as a generic product were low (about 4). Among the other generic
      products, Patell and Nichi-Iko had a pH of about 4.3 while Frestol, Raynanon,
      BMD, and Touchron showed a pH of 4.6-5.2, which was in the pH range of normal
      healthy skin (4.5-6.5). The adhesive force was high (>= 1.38) for Mohrus as a
      brand-name product as well as for Teikoku and Patell as generic products, but it
      was low (<= 0.57) for the other 5 generic products. The water-vapor
      permeabilities of Mohrus as a brand-name product and Teikoku and Patell as
      generic products were low, being less than 1/6 of those for the other 5 generic
      products. Among the 5 generic products, BMD showed the highest water-vapor
      permeability (1,330 g/m2), and the other products also showed a value >= 1,100
      g/m2. The elongatedness of Mohrus was the lowest (15.5 cm), and that of Raynanon
      was the highest (24.5 cm); the difference was 9 cm. In this study, the
      physiochemical and pharmaceutical properties of ketoprofen tapes were clarified,
      which will allow pharmacists to provide products according to the needs of each
      patient when a brand-name product is changed to a generic one.

PMID- 26193947
TI  - Genome-wide characterization and expression analysis of common bean bHLH
      transcription factors in response to excess salt concentration.
AB  - Members of basic helix-loop-helix (bHLH) gene family found in all eukaryotes play
      crucial roles in response to stress. Though, most eukaryotes carry the proteins
      of this family, biological functions of the most bHLH family members are not
      deeply evaluated in plants. In this study, we conducted a comprehensive genome
      wide analysis of bHLH transcription factors in salt tolerant common bean. We
      identified 155 bHLH protein-encoding genes (PvbHLH) by using in silico
      comparative genomics tools. Based on the phylogenetic tree, PvbHLH genes were
      classified into 8 main groups with 21 subfamilies. Exon-intron analysis indicated
      that proteins belonging to same main groups exhibited a closely related gene
      structure. While, the PvbHLH gene family has been mainly expanded through
      segmental duplications, a total of 11 tandem duplication were detected. Genome
      wide expression analysis of bHLH genes showed that 63 PvbHLH genes were
      differentially expressed in at least one tissue. Three of them displayed higher
      expression values in both leaf and root tissues. The in silico micro-RNA target
      transcript analyses revealed that totally 100 PvHLH genes targeted by 86 plant
      miRNAs. The most abundant transcripts, which were targeted by all 18 plant miRNA,
      were belonging to PvHLH-22 and PvHLH-44 genes. The expression of 16 PvbHLH genes
      in the root and leaf tissues of salt-stressed common bean was evaluated using qRT
      PCR. Among them, two of PvbHLHs, PvbHLH-54, PvbHLH-148, were found to be up
      regulated in both tissues in correlation with RNA-seq measurements. The results
      of this study could help improve understanding of biological functions of common
      bean bHLH family under salt stress. Additionally, it may provide basic resources
      for analyzing bHLH protein function for improving economic, agronomic and
      ecological benefit in common bean and other species. 

PMID- 26193948
TI  - Production and secretion of naphthoquinones is mediated by the MFS transporter
      MFS1 in the entomopathogenic fungus Ophiocordyceps sp. BCC1869.
AB  - Naphthoquinones are deep red polyketide pigments produced by the ant-pathogenic
      fungus Ophiocordyceps sp. BCC1869. In culture, biosynthesis of these
      naphthoquinones remains at a low level during the first 20 days and reaches its
      maximum production level at approximately 50 days. The MFS transporter gene MFS1
      was previously identified in Ophiocordyceps sp. BCC1869 from a subtractive EST
      library between the fungus grown under naphthoquinone-inductive and
      naphthoquinone-repressive conditions. We cloned and sequenced this transporter
      gene, which has an open reading frame of 1505 bp and three introns (48, 52, and
      58 bp). Phylogenetic analysis showed this MFS transporter was tightly clustered
      with fungal riboflavin transporters. Functional analysis of this gene was
      performed by overexpression of MFS1 under the control of a strong, constitutive
      promoter. We successfully transformed the fungus with this overexpression plasmid
      using PEG-protoplast transformation, which generated nine transformants per ug of
      plasmid. RT-PCR indicated that the MFS1 expression level in the overexpressing
      strains increased 3- to 10-fold compared to the wild type. HPLC analysis of crude
      extracts of mutants and wild type demonstrated that four naphthoquinone
      derivatives, erythrostominone, epierythrostominol, deoxyerythrostominone, and
      deoxyerythrostominol, were the major naphthoquinones produced and excreted in
      staggering quantities (20- to 2300-fold) in 7-day old liquid cultures by the
      mutant C7, compared to the wild type. High resolution electrospray ionization
      mass spectrometry verified mass spectra of these purified metabolites. Three
      other naphthoquinone derivatives, whose structures have not been identified, were
      also detected in high amount in the mutant liquid cultures.

PMID- 26193950
TI  - Nursing students' understanding and enactment of resilience: a grounded theory
      study.
AB  - AIM: The aim of this study was to explore nursing students' understanding and
      enactment of resilience. BACKGROUND: Stress is considered to be a major factor
      affecting the health, well-being and academic performance of nursing students.
      Resilience has been extensively researched as a process that allows individuals
      to successfully adapt to adversity and develop positive outcomes as a result.
      However, relatively little is known about the resilience of nursing students.
      DESIGN: A constructivist, grounded theory qualitative design was used for this
      study. METHOD: In-depth individual interviews were conducted with 38 nursing
      students enrolled in a four-year, integrated baccalaureate nursing degree
      programme at a university in Ontario, Canada. Face-to-face interviews were
      conducted from January to April 2012 using a semi-structured interview guide.
      FINDINGS: The basic social process of 'pushing through' emerged as nursing
      students' understanding and enactment of resilience. Participants employed this
      process to withstand challenges in their academic lives. This process was
      comprised of three main phases: 'stepping into', 'staying the course' and
      'acknowledging'. 'Pushing through' also included a transient 'disengaging'
      process where students were temporarily unable to push through their adversities.
      The process of 'pushing through' was based on a progressive trajectory, which
      implied that nursing students enacted the process to make progress in their
      academic lives and to attain goals. CONCLUSION: Study findings provide important
      evidence for understanding the phenomenon of resilience as a dynamic, contextual
      process that can be learnt and developed, rather than a static trait or
      personality characteristic.

PMID- 26193949
TI  - Inhibitory effect of totarol on exotoxin proteins hemolysin and enterotoxins
      secreted by Staphylococcus aureus.
AB  - Staphylococcus aureus (S. aureus) causes a wide variety of infections, which are
      of major concern worldwide. S. aureus produces multiple virulence factors,
      resulting in food infection and poisoning. These virulence factors include
      hyaluronidases, proteases, coagulases, lipases, deoxyribonucleases and
      enterotoxins. Among the extracellular proteins produced by S. aureus that
      contribute to pathogenicity, the exotoxins alpha-hemolysin, staphylococcal
      enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) are thought to be of
      major significance. Totarol, a plant extract, has been revealed to inhibit the
      proliferation of several pathogens effectively. However, there are no reports on
      the effects of totarol on the production of alpha-hemolysin, SEA or SEB secreted
      by S. aureus. The aim of this study was to evaluate the effects of totarol on
      these three exotoxins. Hemolysis assay, western blotting and real-time reverse
      transcriptase-PCR assay were performed to identify the influence of graded
      subinhibitory concentrations of totarol on the production of alpha-hemolysin and
      the two major enterotoxins, SEA and SEB, by S. aureus in a dose-dependent manner.
      Moreover, an enzyme linked immunosorbent assay showed that the TNF-alpha
      production of RAW264.7 cells stimulated by S. aureus supernatants was inhibited
      by subinhibitory concentrations of totarol. Form the data, we propose that
      totarol could potentially be used as a promising natural compound in the food and
      pharmaceutical industries. 

PMID- 26193951
TI  - Health-Related Quality of Life in the Aftermath of the L'Aquila Earthquake in
      Italy.
AB  - OBJECTIVE: A recent article reported a reduction in the suicide rate in the
      inhabitants of L'Aquila (Italy) in 2009, when on the night of April 6, a
      devastating earthquake struck the city. The potential implications of the role of
      resilience in the aftermath of natural disasters, together with the limitations
      of existing evidence on this topic, suggest a need for more research. We aimed to
      retrospectively investigate the impact of the L'Aquila earthquake on a
      standardized self-reported measure of health-related quality of life (HRQoL).
      METHODS: HRQoL data were collected through 2 separate cross-sectional surveys
      conducted during 2008 and 2010, before and after the earthquake that occurred in
      2009, on 2 random samples of adults living in L'Aquila. RESULTS: The data seemed
      to suggest no decrease in the inhabitants' HRQoL level after the disaster, which
      may suggest the role of resilience in supporting survivors' HRQoL. The findings
      were also consistent with previous observations of a reduction in the suicide
      rate in the same inhabitants after the earthquake. CONCLUSIONS: After a natural
      disaster, people likely activate personal resources and protective social factors
      that result in better subjective outcomes.

PMID- 26193952
TI  - The co-expression of GPER and Gankyrin in ovarian endometriosis and its
      correlation with the rASRM stages.
AB  - OBJECTIVE: The aim of this study was to examine the expression of G protein
      coupled estrogen receptor (GPER) and Gankyrin in ovarian endometriosis, analyze
      their clinicopathological significance, and investigate their correlation.
      METHODS: Quantitative real-time polymerase chain reaction and Western blot were
      performed to testify mRNA and protein expression of GPER and Gankyrin in ovarian
      endometriosis. Immunohistochemical staining (streptavidin-peroxidase method) was
      conducted to determine the expression and distribution of GPER and Gankyrin
      protein in matched ectopic and eutopic endometrium of endometriosis and normal
      endometrium. We also investigated their associations with rASRM stages and the
      correlation between the two proteins. RESULTS: GPER and Gankyrin were found
      overexpressed in ectopic endometrium of endometriosis compared with either its
      eutopic counterpart or endometrium from normal patients. The immunohistochemical
      analysis also revealed that higher expression was observed in eutopic endometrium
      with or without endometriosis during proliferative phase in comparison to
      secretory phase. These two proteins were positively correlated with the stages of
      endometriosis. Moreover, a significant positive correlation was found between
      GPER and Gankyrin both in ectopic and eutopic endometrium of the ovarian
      endometriosis. CONCLUSION: GPER and Gankyrin might be implicated in the hormonal
      regulation of endometriosis and be associated with the severity of endometriosis.
      In addition, GPER and Gankyrin were found to be positively correlated, which
      could possibly serve as novel therapeutic targets for this disease.

PMID- 26193953
TI  - Pelvic floor muscle electromyography during different running speeds: an
      exploratory and reliability study.
AB  - PURPOSE: Stress urinary incontinence (SUI) affects women of all ages including
      young athletes, especially those involved in high-impact sports. To date, hardly
      any studies are available testing pelvic floor muscles (PFM) during sports
      activities. The aim of this study was the description and reliability test of six
      PFM electromyography (EMG) variables during three different running speeds. The
      secondary objective was to evaluate whether there was a speed-dependent
      difference between the PFM activity variables. METHODS: This trial was designed
      as an exploratory and reliability study including ten young healthy female
      subjects to characterize PFM pre-activity and reflex activity during running at
      7, 9 and 11 km/h. Six variables for each running speed, averaged over ten steps
      per subject, were presented descriptively, tested regarding their reliability
      (Friedman, ICC, SEM, MD) and speed difference (Friedman). RESULTS: PFM EMG
      variables varied between 67.6 and 106.1 %EMG, showed no systematic error and were
      low for SEM and MD using the single value model. Applying the average model over
      ten steps, ICC (3,k) were >0.75 and SEM and MD about 50 % lower than for the
      single value model. Activity was found to be highest in 11 km/h. CONCLUSION: EMG
      variables showed excellent ICC and very low SEM and MD. Further studies should
      investigate inter-session reliability and PFM reactivity patterns of SUI patients
      using the average over ten steps for each variable as it showed very high ICC and
      very low SEM and MD. Subsequently, longer running distances and other high-impact
      sports disciplines could be studied.

PMID- 26193954
TI  - Development of obstetrical and gynecological journals, 2007 to 2013: a trend
      analysis.
AB  - PURPOSE: To analyze the trends and developments among journals in the specialty
      of obstetrics and gynecology. METHODS: Using the Journal Citation Reports from
      2007 to 2013, we analyzed the impact factor (IF), Eigenfactor(r) Score (ES), and
      Article Influence(r) Score (AIS) of 43 journals in the field of obstetrics and
      gynecology published in this time period. RESULTS: From 78 journals of the
      Journal Citation Report 2013, 43 were selected for this study. The mean IF grew
      from 1.68 +/- 0.97 in 2007 to 2.12 +/- 1.05 in 2013, the ES from 0.0113 +/-
      0.0169 to 0.0114 +/- 0.0140, and the AIS from 0.513 +/- 0.302 to 0.663 +/- 0.359.
      Differences in the IF, ES, and AIS between journals from the United States versus
      Europe could be observed. In most cases, the IF, ES, and AIS increased between
      2007 and 2013. Strong correlations could be found between IF, AIS, and ES.
      CONCLUSIONS: The overall mean IF for obstetrical and gynecological journals
      increased over the analyzed time period. The IF remains the standard measure to
      compare scientific journals. It correlates well with two major alternative
      measures of scientific impact, the ES and especially the AIS. Other measures are
      evolving and might show superior usage in the future.

PMID- 26193955
TI  - Fetal heart rate patterns of pregnancies with vasa previa and velamentous cord
      insertion.
AB  - OBJECTIVE: To investigate the fetal heart rate (FHR) patterns in pregnancies
      complicated with vasa previa and velamentous cord insertion (VCI). METHODS: A
      retrospective study comparing FHR patterns in pregnancies and subsequent
      pregnancies with/without VCI and in pregnancies with/without vasa previa was
      conducted. For each patient, FHR patterns were compared to the subsequent
      pregnancy. Deliveries occurred between the years 1988 and 2012 in a tertiary
      medical center. FHR patterns were evaluated according to the ACOG guidelines.
      RESULTS: During the study period, there were 184 pregnancies with VCI and 37
      pregnancies with vasa previa, undetected during pregnancy. FHR patterns of the
      VCI group included more cases of abnormal baseline (7 vs. 2 %, p < 0.05), out of
      which 7 % were fetal tachycardia (vs. 2 %) and 4 % were bradycardia (vs. 1 %).
      There were also more cases of abnormal baseline and abnormal variability (7 vs. 2
      % and 32 vs. 22 %, respectively, p < 0.05) in the VCI group. FHR categories also
      differed between the velamentous cord insertion pregnancies and subsequent ones.
      VCI pregnancies had more category 2 patterns, not statistically significant (64
      vs. 55 %, p = 0.11). FHR patterns of the vasa previa group included more cases of
      abnormal baseline (27 vs. 7 %, p < 0.05), out of which 18 % were tachycardia and
      9 % were bradycardia. Decelerations were recorded in a total of 61 % of the vasa
      previa cases (61 vs. 31 %, p = 0.02), most of which were variable decelerations
      (48 vs. 17 %). Vasa previa pregnancies had more category 2 patterns (64 vs. 52
      %). CONCLUSIONS: Fetal heart rate patterns in pregnancies complicated with VCI or
      vasa previa have several non-specific pathological characteristics; none can be
      used for early detection of these conditions.

PMID- 26193956
TI  - Biocompatible porcine dermis graft to treat severe cystocele: impact on quality
      of life and sexuality.
AB  - PURPOSE: To study the quality of life (QoL) and sexual function changes of women
      affected by severe cystocele treated using biocompatible porcine dermis graft.
      METHODS: 20 women (ranging in age from 47 to 71 years, mean age 58.7) with third-
      and fourth-degree cystocele (according to Baden and Walker classification) were
      enrolled. The Short Form-36 questionnaire to assess QoL was administrated at
      baseline and 12 months after surgical treatment. The Pelvic Organ
      Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) to measure the
      changes of sexual behavior was used at baseline and 12 months after surgical
      treatment. Each woman underwent translabial color Doppler ultrasonography to
      measure the clitoral blood flow before and 12 months after surgical treatment.
      RESULTS: Women reported QoL improvement (P < 0.001). By PISQ-12, improvement of
      the behavioral emotive factor score, the physical factor score, the partner
      related factor score and of the total score during the 12-month follow-up with
      respect to baseline experience was observed (P < 0.001). Color Doppler
      measurement showed that the mean pulsatility index, peak systolic velocity,
      resistance index and end-diastolic velocity of clitoral arteries did not
      significantly change (P = NS). CONCLUSIONS: Biocompatible porcine dermis graft to
      treat severe cystocele considerably improves QoL and sexual function, and does
      not influence clitoral blood flow. Our data could add new information about
      sexual behavior after prolapse treatment using this kind of graft, particularly
      about the impact on clitoral blood flow changes.

PMID- 26193957
TI  - Effects of scanner acoustic noise on intrinsic brain activity during auditory
      stimulation.
AB  - INTRODUCTION: Although the effects of scanner background noise (SBN) during
      functional magnetic resonance imaging (fMRI) have been extensively investigated
      for the brain regions involved in auditory processing, its impact on other types
      of intrinsic brain activity has largely been neglected. The present study
      evaluated the influence of SBN on a number of intrinsic connectivity networks
      (ICNs) during auditory stimulation by comparing the results obtained using sparse
      temporal acquisition (STA) with those using continuous acquisition (CA). METHODS:
      Fourteen healthy subjects were presented with classical music pieces in a block
      paradigm during two sessions of STA and CA. A volume-matched CA dataset (CAm) was
      generated by subsampling the CA dataset to temporally match it with the STA data.
      Independent component analysis was performed on the concatenated STA-CAm
      datasets, and voxel data, time courses, power spectra, and functional
      connectivity were compared. RESULTS: The ICA revealed 19 ICNs; the auditory,
      default mode, salience, and frontoparietal networks showed greater activity in
      the STA. The spectral peaks in 17 networks corresponded to the stimulation cycles
      in the STA, while only five networks displayed this correspondence in the CA. The
      dorsal default mode and salience networks exhibited stronger correlations with
      the stimulus waveform in the STA. CONCLUSIONS: SBN appeared to influence not only
      the areas of auditory response but also the majority of other ICNs, including
      attention and sensory networks. Therefore, SBN should be regarded as a serious
      nuisance factor during fMRI studies investigating intrinsic brain activity under
      external stimulation or task loads.

PMID- 26193958
TI  - Detection of subgingival periodontal pathogens--comparison of two sampling
      strategies.
AB  - OBJECTIVE: The aim of the study is to compare detection frequency of periodontal
      pathogens in patients with aggressive/severe chronic periodontitis using pooled
      plaque samples from the deepest pockets per quadrant/per sextant. METHODS: In 100
      patients with aggressive/chronic periodontitis, subgingival plaque was sampled
      from the deepest pockets per quadrant (MT4) and per sextant (MT6). Plaque samples
      were taken using two sterile paper points simultaneously. One paper point from
      each pocket was pooled with the three other paper points of the pockets (MT4).
      Subsequently, the remaining four paper points were pooled with two paper points
      from the deepest pockets from the two remaining sextants (MT6). The content of
      each vial was analyzed with nucleic-acid based methods for Aggregatibacter
      actinomycetemcomitans, Tannerella forsythia, Porphyromonas gingivalis, Treponema
      denticola, Prevotella intermedia, Parvimonas micra, Fusobacterium nucleatum,
      Campylobacter rectus, Eubacterium nodatum, Eikenella corrodens, and
      Capnocytophaga sp. RESULTS: The detection frequency of A. actinomycetemcomitans
      (MT4/MT6) at 22/24 %, T. forsythia at 93/96 %, P. gingivalis at 78/79 %, T.
      denticola at 88/90 %, P. intermedia at 40/46 %, P. micra at 75/79 %, F. nucleatum
      at both 99 %, C. rectus at 84/89 %, E. nodatum at 62/65 %, E. corrodens at 80/87
      %, and Capnocytophaga sp. at 49/58 % was higher with MT6 than with MT4. None of
      these differences were statistically significant. CONCLUSION: The detection
      frequency of the investigated periopathogens was statistically insignificant
      higher with the sampling method MT6 compared with MT4. CLINICAL RELEVANCE: In
      daily dental practice, the plaque sampling of the deepest pockets per quadrant
      seems to be sufficient.

PMID- 26193959
TI  - Identification and characterization of cis- and trans-acting elements involved in
      prophage induction in Streptococcus thermophilus J34.
AB  - The genetic switch region of temperate Streptococcus thermophilus phage TP-J34
      contains two divergently oriented promoters and several predicted operator sites.
      It separates lytic cycle-promoting genes from those promoting lysogeny. A
      polycistronic transcript comprises the genes coding for repressor Crh,
      metalloproteinase-motif protein Rir and superinfection exclusion lipoprotein Ltp.
      Weak promoters effecting monocistronic transcripts were localized for ltp and int
      (encoding integrase) by Northern blot and 5'-RACE-PCR. These transcripts appeared
      in lysogenic as well as lytic state. A polycistronic transcript comprising genes
      coh (encoding Cro homolog), ant (encoding putative antirepressor), orf7, orf8 and
      orf9 was only detected in the lytic state. Four operator sites, of which three
      were located in the intergenic regions between crh and coh, and one between coh
      and ant, were identified by competition electromobility shift assays. Cooperative
      binding of Crh to two operator sites immediately upstream of coh could be
      demonstrated. Coh was shown to bind to the operator closest to crh only.
      Oligomerization was proven by cross-linking Crh by glutaraldehyde. Knock-out of
      rir revealed a key role in prophage induction. Rir and Crh were shown to form a
      complex in solution and Rir prevented binding of Crh to its operator sites. 

PMID- 26193960
TI  - Vascular alterations in apolipoprotein A-I amyloidosis (Leu75Pro). A case-control
      study.
AB  - BACKGROUND: Among hereditary amyloidoses, apolipoprotein A-I (APO A-I)
      amyloidosis (Leu75Pro) is a rare, autosomal dominant condition in which renal,
      hepatic, and testicular involvement has been demonstrated. OBJECTIVE: To
      investigate vascular structural as well as functional alterations. METHODS: In
      131 carriers of the amyloidogenic Leu75Pro APO A-I mutation (mean age 52 + 16
      years, 56 women) and in 131 subjects matched for age, sex, body mass index and
      clinic blood pressure (BP), arterial stiffness (pulse wave velocity, PWV) and
      carotid intima-media thickness (IMT) were measured. RESULTS: By definition no
      differences for age, sex, body mass index, and BP were observed. Meanmax IMT
      (Mmax-IMT) in the common (CC), bifurcation (BIF) and internal (ICA) carotid
      artery were comparable in the two groups. After adjustment for high-density
      lipoprotein cholesterol and renal function differences between the two groups, a
      lower meanmax-IMT was observed in APO A-I Leu75Pro mutation carriers than in
      controls (CC Mmax-IMT 0.87 +/- 0.21 versus 0.93 +/- 0.2 mm, p = 0.07; BIF Mmax
      IMT 1.19 +/- 0.48 versus 1.36 +/- 0.46 mm, p = 0.025; ICA Mmax-IMT 0.9 +/- 0.37
      versus 1.02 +/- 0.35 mm, p = 0.028). On the other hand, aortic stiffness was
      significantly greater in patients with APO A-I amyloidosis than controls (PWV
      11.5 +/- 2.9 and 10.7 +/- 2.3 m/s, p < 0.05), even after adjusting for
      confounders. CONCLUSIONS: In carriers of the amyloidogenic Leu75Pro APO A-I
      mutation, a significant increase in arterial stiffness is observed; on the
      contrary, carotid artery IMT is comparable to that of control subjects. These
      results may add significant information to the clinical features of this rare
      genetic disorder.

PMID- 26193961
TI  - Personalized medicine approach for optimizing the dose of tafamidis to
      potentially ameliorate wild-type transthyretin amyloidosis (cardiomyopathy).
AB  - Placebo-controlled clinical trials are useful for identifying the dose of a drug
      candidate that produces a meaningful clinical response in a patient population.
      Currently, Pfizer, Inc. is enrolling a 400-person clinical trial to test the
      efficacy of 20 or 80 mg of tafamidis to ameliorate transthyretin (TTR)-associated
      cardiomyopathy using clinical endpoints. Herein, we provide guidance for how to
      optimize the dose of tafamidis for each WT TTR cardiomyopathy patient using its
      mechanism of action as the key readout, i.e. we identify the dose of tafamidis
      that maximally kinetically stabilizes TTR in the blood. Tetramer dissociation is
      rate limiting for TTR aggregation, which appears to drive the pathology of the
      TTR amyloidoses. Hence, we measure the TTR tetramer dissociation rate (kinetic
      stability) in the patient's plasma as a function of tafamidis dose to optimize
      the dose employed to maximize kinetic stability. Historical data tell us that a
      subset of patients exhibiting higher tafamidis plasma concentrations are
      maximally kinetically stabilized at the 20-mg tafamidis dose, whereas the patient
      studied herein required a 60 mg once daily dose to achieve maximum kinetic
      stabilization. We anticipate that establishing the dose of tafamidis that
      achieves maximal TTR kinetic stabilization will translate into a maximal clinical
      effect, but that remains to be demonstrated. 

PMID- 26193962
TI  - Drug Sensitivity Testing in Cytoreductive Surgery and Intraperitoneal
      Chemotherapy of Pseudomyxoma Peritonei.
AB  - BACKGROUND: Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) is
      an established therapy for pseudomyxoma peritonei (PMP). However, the role of IPC
      is unclear. By ex vivo assessment of PMP tumor cell sensitivity to cytotoxic
      drugs, we investigated the basis for IPC drug selection and the role of IPC in
      the management of PMP. METHODS: Tumor cells were prepared by collagenase
      digestion of tumor tissue from 133 PMP patients planned for CRS and IPC. Tumor
      cell sensitivity to oxaliplatin, 5FU, mitomycin C, doxorubicin, irinotecan, and
      cisplatin was assessed in a 72-h cell-viability assay. Drug sensitivity was
      correlated to progression-free survival (PFS) and overall survival (OS). RESULTS:
      Samples from 92 patients were analyzed successfully. Drug sensitivity varied
      considerably between samples. Peritoneal mucinous carcinomatosis (PMCA), compared
      with PMCA intermediate or disseminated peritoneal adenomucinosis, was slightly
      more resistant to platinum and 5FU and tumor cells from patients previously
      treated with chemotherapy were generally less sensitive than those from untreated
      patients. Multivariate analysis showed patient performance status and
      completeness of CRS to be prognostic for OS. Among patients with complete CRS (n
      = 61), PFS tended to be associated with sensitivity to mitomycin C and cisplatin
      (p ~ 0.06). At the highest drug concentration tested, the hazard ratio for
      disease relapse increased stepwise with drug resistance for all drugs.
      CONCLUSIONS: Ex vivo assessment of drug sensitivity in PMP provides prognostic
      information. The results suggest a role for IPC as therapeutic adjunct to CRS and
      for individualization of IPC by pretreatment assessment of drug sensitivity.

PMID- 26193963
TI  - Skin Flap Necrosis After Mastectomy With Reconstruction: A Prospective Study.
AB  - BACKGROUND: Rates of mastectomy with immediate reconstruction are rising. Skin
      flap necrosis after this procedure is a recognized complication that can have an
      impact on cosmetic outcomes and patient satisfaction, and in worst cases can
      potentially delay adjuvant therapies. Many retrospective studies of this
      complication have identified variable event rates and inconsistent associated
      factors. METHODS: A prospective study was designed to capture the rate of skin
      flap necrosis as well as pre-, intra-, and postoperative variables, with follow
      up assessment to 8 weeks postoperatively. Uni- and multivariate analyses were
      performed for factors associated with skin flap necrosis. RESULTS: Of 606
      consecutive procedures, 85 (14 %) had some level of skin flap necrosis: 46 mild
      (8 %), 6 moderate (1 %), 31 severe (5 %), and 2 uncategorized (0.3 %). Univariate
      analysis for any necrosis showed smoking, history of breast augmentation, nipple
      sparing mastectomy, and time from incision to specimen removal to be significant.
      In multivariate models, nipple-sparing, time from incision to specimen removal,
      sharp dissection, and previous breast reduction were significant for any
      necrosis. Univariate analysis of only moderate or severe necrosis showed body
      mass index, diabetes, nipple-sparing mastectomy, specimen size, and expander size
      to be significant. Multivariate analysis showed nipple-sparing mastectomy and
      specimen size to be significant. Nipple-sparing mastectomy was associated with
      higher rates of necrosis at every level of severity. CONCLUSIONS: Rates of skin
      flap necrosis are likely higher than reported in retrospective series. Modifiable
      technical variables have limited the impact on rates of necrosis. Patients with
      multiple risk factors should be counseled about the risks, especially if they are
      contemplating nipple-sparing mastectomy.

PMID- 26193964
TI  - Incidental and Intentional Medicine Achieve Similar Results in Primary
      Hyperaldosteronism.
AB  - BACKGROUND: Primary hyperaldosteronism is a common cause of hypertension, with
      significant cardiovascular, renal, and metabolic sequelae. Delayed diagnosis of
      primary hyperaldosteronism can lead to severe disease and lower cure rates after
      adrenalectomy. This study investigated the presentation and outcomes of patients
      who had primary hyperaldosteronism diagnosed after incidental discovery of an
      adrenal mass. METHODS: A retrospective cohort study investigated patients
      receiving adrenalectomy for primary hyperaldosteronism at the authors'
      institution from 2001 to 2014. Patients were classified as nonincidental if the
      aldosteronoma was identified on imaging performed for a hypertension or
      hypokalemia workup or after a biochemical diagnosis or as incidental if the
      aldosteronoma was identified on imaging performed for any other reason.
      Nonincidental and incidental patients were compared in terms of patient
      demographics, clinical history, preoperative test results, surgical pathology
      findings, and postoperative course. RESULTS: The study included 210 patients, 17
      (8.1 %) of whom were incidental. At the time of surgical evaluation, 88 % of the
      incidental patients met the criteria for primary hyperaldosteronism screening
      based on hypokalemia or the degree of hypertension. The incidental patients were
      younger than the nonincidental patients, but the two groups were otherwise
      demographically and clinically similar. The incidental patients had larger
      aldosteronomas than the nonincidental patients. The nonincidental and incidental
      patients had similar rates of postoperative cure and failure. CONCLUSIONS:
      Nonincidental and incidental patients have comparable disease severity before
      surgical evaluation and similar rates of postoperative cure. Increased adherence
      to guidelines for screening of primary hyperaldosteronism will lead to a more
      timely diagnosis for all patients and a higher potential for surgical cure.

PMID- 26193965
TI  - Discordance of Histologic Grade Between Primary and Metastatic Neuroendocrine
      Carcinomas.
AB  - BACKGROUND: The prognosis and management of neuroendocrine carcinoma are largely
      driven by histologic grade as assessed by mitotic activity. The authors reviewed
      their institutional experience to determine whether the histologic grade of
      neuroendocrine carcinoma can differ between primary and metastatic tumors.
      METHODS: This study examined patients who underwent operative resection of both
      primary and metastatic foci of neuroendocrine carcinoma. Resected tumors were
      independently reviewed and categorized as low, intermediate, or high grade as
      determined by mitotic count. RESULTS: The authors identified 20 patients with
      metastatic neuroendocrine carcinoma treated at their institution between 1997 and
      2013 for whom complete pathologic review of primary and metastatic tumors was
      possible. Primary lesions were found in the small intestine (n = 12), pancreas (n
      = 7), ampulla (n = 1), stomach (n = 1), and rectum (n = 1). The timing of hepatic
      metastasis was synchronous in 15 cases and metachronous in 5 cases. The
      histologic grade was concordant between primary and metastatic tumors in 9 cases
      and discordant in 11 cases. Among the discordant cases, 7 had a higher metastatic
      grade than primary grade, and 4 had a lower metastatic grade than primary grade.
      Metachronous presentation was associated with a higher likelihood of grade
      discordance (p = 0.03). The histologic grade of all metachronous metastases
      differed from that of the primary tumors. CONCLUSION: There is a high prevalence
      of histologic grade discordance between primary and metastatic foci of
      neuroendocrine carcinoma, particularly among patients with a metachronous
      metastatic presentation. Given the importance of histologic grade in disease
      prognostication and treatment planning, this finding may be informative for the
      management of patients with metastatic neuroendocrine carcinoma.

PMID- 26193966
TI  - Current Trends and Emerging Future of Indocyanine Green Usage in Surgery and
      Oncology: An Update.
AB  - BACKGROUND: Indocyanine green (ICG) is a widely available dye of clinical
      importance that has been used for more than 50 years. Near-infrared (NIR) ICG
      fluorescence imaging has found a niche in cancer care since 2005, and was
      reviewed in 2011. There is a need for a comprehensive update and we aim to
      provide this through a review of the most recent literature. METHODS: A
      systematic review of the literature using PubMed, EMBASE, and MEDLINE databases
      of articles published from 2000 to June 2015 evaluated topics pertinent to NIR
      fluorescence imaging with ICG in the diagnosis and surgical treatment of cancer.
      Articles previously referenced in a 2011 review and a 2015 meta-analysis were
      excluded, while articles that referenced future directions and economics were
      included in this current review. RESULTS: Since 2011, the literature has grown
      exponentially, with significant advances at the molecular level. Significant
      findings from 89 select articles and 10 reviews, most of which were published
      between 2011 and 2015, are summarized. Preclinical studies are currently underway
      investigating tumor-specific fluorescence and targeted therapeutic delivery. The
      potential for ICG exists at every level of cancer care, from diagnosis to
      surveillance. CONCLUSION: The indications, applications, and potential for ICG
      have grown exponentially in the past decade; an updated review of the literature
      is overdue and we present the most comprehensive review to date.

PMID- 26193967
TI  - Potential Unintended Consequences of a Conservative Management Strategy for
      Patent Ductus Arteriosus.
AB  - BACKGROUND: A recent review supports a strategy of deferring treatment of patent
      ductus arteriosus (PDA) in the preterm neonate until at least the second week
      after birth. In light of previous suggestion that later initiation of treatment
      may be less efficacious for closing PDAs it is reasonable to question if delayed
      treatment may be less effective. DESIGN: We conducted a single center
      retrospective review of a neonatal intensive care unit database of infants <=37
      weeks gestation with the diagnosis of PDA and treated with indomethacin from 1999
      to 2007. We determined gestational age (GA), timing of indomethacin initiation,
      and status of the PDA at hospital discharge. Treatment failure was defined as
      neonates requiring further intervention to close their PDA or those who died
      without echo-proven PDA closure. RESULTS: Of the 341 infants meeting the study
      criteria, 77 (23%) had defined treatment failure. The failure group had a younger
      median GA of 25 weeks (interquartile range [IQR], 24-26) vs. 28 weeks (IQR, 26
      30) for the successful group (P < .0001). The failure group had a median
      treatment initiation on day of life (DOL) 4 (IQR, 1-8) compared with DOL 3 (IQR,
      1-6) for those in the successful group (P = .15). Taken as a whole, infants
      treated after DOL 5 were significantly more likely to have treatment failure
      (30.1% vs. 19.3% for those treated DOL 1-5, P = .03). CONCLUSIONS: Our study
      confirms that younger GA at birth is correlated with increased likelihood of
      failed PDA closure. We also show a trend indicating that later initiation of
      treatment may decrease the chances of successfully closing a PDA. Future
      examination of PDA management should consider the potential unintended
      consequences that may accompany a delayed treatment strategy.

PMID- 26193968
TI  - [Cement augmentation on the spine : Biomechanical considerations].
AB  - BACKGROUND: Vertebral compression fractures are the most common osteoporotic
      fractures. Since the introduction of vertebroplasty and screw augmentation, the
      management of osteoporotic fractures has changed significantly. AIMS: The
      biomechanical characteristics of the risk of adjacent fractures and novel
      treatment modalities for osteoporotic vertebral fractures, including pure cement
      augmentation by vertebroplasty, and cement augmentation of screws for posterior
      instrumentation, are explored. MATERIALS AND METHODS: Eighteen human osteoporotic
      lumbar spines (L1-5) adjacent to vertebral bodies after vertebroplasty were
      tested in a servo-hydraulic machine. As augmentation compounds we used standard
      cement and a modified low-strength cement. Different anchoring pedicle screws
      were tested with and without cement augmentation in another cohort of human
      specimens with a simple pull-out test and a fatigue test that better reflects
      physiological conditions. RESULTS: Cement augmentation in the osteoporotic spine
      leads to greater biomechanical stability. However, change in vertebral stiffness
      resulted in alterations with the risk of adjacent fractures. By using a less firm
      cement compound, the risk of adjacent fractures is significantly reduced. Both
      screw augmentation techniques resulted in a significant increase in the
      withdrawal force compared with the group without cement. Augmentation using
      perforated screws showed the highest stability in the fatigue test. DISCUSSION
      AND CONCLUSION: The augmentation of cement leads to a significant change in the
      biomechanical properties. Differences in the stability of adjacent vertebral
      bodies increase the risk of adjacent fractures, which could be mitigated by a
      modified cement compound with reduced strength. Screws that were specifically
      designed for cement application displayed greatest stability in the fatigue test.

PMID- 26193969
TI  - [Periprosthetic knee infection after a cat bite].
AB  - BACKGROUND: Infections caused by Pasteurella multocida are extremely rare in
      arthroplasty. We report the case of a patient who was bitten by his domestic cat,
      causing an infection of his knee arthroplasty. DIAGNOSIS AND TREATMENT: The
      puncture of the knee resulted in putrid joint effusion. After removal of the knee
      prosthesis, infection with Pasteurella multocida was verified. We performed a two
      stage revision combined with intravenous antibiotic therapy. DISCUSSION:
      Infections caused by cats and dogs should attract more attention especially as
      prosthesis material represents a significant "locus minoris resistentiae".
      Patients with domestic pets should be informed about this source of infection and
      possible complications. In the case of a bite, prompt and liberal antibiotic
      treatment should be administered.

PMID- 26193970
TI  - 'Smart' nanoparticles as drug delivery systems for applications in tumor therapy.
AB  - INTRODUCTION: In the therapy of clinical diseases such as cancer, it is important
      to deliver drugs directly to tumor sites in order to maximize local drug
      concentration and reduce side effects. This objective may be realized by using
      'smart' nanoparticles (NPs) as drug delivery systems, because they enable
      dramatic conformational changes in response to specific physical/chemical stimuli
      from the diseased cells for targeted and controlled drug release. AREAS COVERED:
      In this review, we first briefly summarize the characteristics of 'smart' NPs as
      drug delivery systems in medical therapy, and then discuss their targeting
      transport, transmembrane and endosomal escape behaviors. Lastly, we focus on the
      applications of 'smart' NPs as drug delivery systems for tumor therapy. EXPERT
      OPINION: Biodegradable 'smart' NPs have the potential to achieve maximum efficacy
      and drug availability at the desired sites, and reduce the harmful side effects
      for healthy tissues in tumor therapy. It is necessary to select appropriate NPs
      and modify their characteristics according to treatment strategies of tumor
      therapy.

PMID- 26193971
TI  - Sixty Girls, Three Nuns, One Home.
AB  - This article describes the experience of a nurse volunteer working with girls in
      India who had been trafficked and/or were children of mothers who were (are)
      prostitutes. The article describes how nuns who care, provide values and a safe
      home give the girls opportunities. The article illustrates how, with little
      recourse, three nuns care for 60 girls living in one home. The girls range in age
      from 4 to 18 years. The girls are motivated to live happily, work hard, study
      often, and play together. Lessons learned from the nurse volunteer who worked and
      lived with the girls are described. This article illustrates how nurses in
      retirement can still fulfill their passion of helping others. 

PMID- 26193972
TI  - Uptake of inorganic phosphorus by temperate seagrass beds of Posidonia and
      Amphibolis in Southern Australia.
AB  - Seagrasses occupy a narrow band of sandy seabed close to the coast and are
      therefore vulnerable to anthropogenic influences, particularly meadows near large
      population centres. Over 5000 ha of seagrasses have been lost from Adelaide
      coastal waters (South Australia) over the past 70 years and much of this loss has
      been attributed to nutrient inputs from wastewater, industrial and stormwater
      discharges. This led to the Adelaide Coastal Waters Study to understand processes
      along the Adelaide metropolitan coast that led to seagrass loss. This study, a
      subset of the larger ACWS study, used in situ nutrient spike approach to obtain
      ecologically relevant estimates of seasonal variability in phosphorus uptake in
      two species of temperate seagrass common to this coast (Amphibolis antarctica and
      Posidonia angustifolia). Total uptake of phosphorus by biological components in
      the seagrass beds, viz., seagrass, epiphytes and phytoplankton, was negligible,
      never exceeding 0.5% of the total resource. Phosphorus uptake rate varied
      seasonally with higher rates in winter (1.49 MUmol P.g(-1) DW.h(-1)) and lower
      rates in spring (0.70 MUmol P.g(-1) DW.h(-1)) for Amphibolis and highest in
      winter (2.09 MUmol P.g(-1) DW.h(-1)) and least in spring (0.14 MUmol P.g(-1)
      DW.h(-1)) for Posidonia. Low biological uptake rates of inorganic phosphorus
      could be attributed to carbonate sediments and particulates in the water column
      binding inorganic phosphorus, limiting its availability for biological uptake.
      From an environmental perspective, seagrass beds in the Adelaide coastal waters
      account for the assimilation of only 5.4% (19.53 t yr(-1)) of the total
      anthropogenic inputs of phosphorus.

PMID- 26193973
TI  - Determination of Human Hemoglobin Derivatives.
AB  - The levels of the inactive hemoglobin (Hb) pigments [such as methemoglobin
      (metHb), carboxyhemoglobin (HbCO) and sulfohemoglobin (SHb)] and the active Hb
      [in the oxyhemoglobin (oxyHb) form] as well as the blood Hb concentration in
      healthy non pregnant female volunteers were determined using a newly developed
      multi-component spectrophotometric method. The results of this method revealed
      values of SHb% in the range (0.0727-0.370%), metHb% (0.43-1.0%), HbCO% (0.4
      1.52%) and oxyHb% (97.06-98.62%). Furthermore, the results of this method
      revealed values of blood Hb concentration in the range (12.608-15.777 g/dL). The
      method is highly sensitive, accurate and reproducible. 

PMID- 26193974
TI  - beta-Thalassemia Intermedia Associated with Heterozygous and Isolate beta-Globin
      Gene Mutation [IVS-II-1 (HBB: c.315G>A)].
AB  - A 4-year-old male child of Caucasian ethnicity was investigated for moderate
      hemolytic and non immune-mediated anemia. The presence of splenomegaly and the
      elevation of Hb A(2) and Hb F and the exclusion of a defect of protein of red
      blood cell (RBC) membranes defined a clinical picture of beta-thalassemia
      intermedia (beta-TI). The molecular analysis showed a heterozygous IVS-II-1 (HBB:
      c.315G > A) mutation on the beta-globin gene, in the absence of extra alpha
      globin genes or unstable hemoglobin (Hb) chains.

PMID- 26193975
TI  - Experimental Characterization of Hb Flurlingen (HBA2: c.177 C > G, p.His > Gln)
      and Hb Boghe (HBA2: c.177 C > A, p.His > Gln) Reveals Contradictory HBA2
      Expression and Translation Patterns Despite Identical Amino Acid Substitutions.
AB  - In this study, we describe the clinical features and provide experimental
      analyses of Hb Flurlingen (HBA2: c.177 C > G, p.His > Gln) that contrasted with
      Hb Boghe (HBA2: c.177 C > A, p.His > Gln). Despite the identical amino acid
      substitution in both variants, Hb Flurlingen shows the phenotype of alpha
      thalassemia (alpha-thal), whereas Hb Boghe has no impact on alpha2-globin (HBA2)
      production. For in vitro transcription analysis, HBA2 expression constructs
      carrying the HBA2-WT (wild type), Hb Flurlingen and Hb Boghe sequences were
      generated and expressed in human bladder carcinoma 5637 cells for downstream
      analyses by quantitative real time-polymerase chain reaction (qReTi-PCR) and
      immunofluorochemistry (IFC). In silico analysis of secondary folding structures
      of the HBA2-WT, Hb Flurlingen and Hb Boghe mRNA sequences was performed using
      Mfold software. The gene transcription and translation analyses revealed that
      cells transfected with the Hb Flurlingen construct had significantly lower HBA2
      transcription (-55.4%, p <= 0.01) and reduced protein synthesis when compared to
      the wild type group. In contrast, cells transfected with the Hb Boghe construct
      showed no significant changes in HBA2 transcription or translation activities
      when compared to the wild type group. The in silico prediction of possible
      effects of these mutations on the folding structures of the HBA2 transcripts
      showed a change of secondary folding pattern in the Hb Flurlingen transcript when
      compared to those of HBA2-WT and Hb Boghe. Our experimental findings support the
      clinical presentation of an alpha-thalassemic phenotype for Hb Flurlingen in
      contrast with Hb Boghe, despite identical amino acid substitutions. The results
      confirm the importance of experimental analysis in establishing the impact of
      novel base substitutions. 

PMID- 26193976
TI  - The Prevalence and Spectrum of alpha-Thalassemia in Guizhou Province of South
      China.
AB  - alpha-Thalassemia (alpha-thal) is one of the most prevalent genetic diseases in
      the world and is especially frequent in tropical and subtropical regions,
      including South China. The aim of this study was to investigate the prevalence
      and spectrum of alpha-thal in Guizhou Province as this information was unknown. A
      total of 40 alpha-thal carriers were determined in 1219 newborn umbilical cord
      blood samples by hemoglobin (Hb) electrophoresis combined with DNA analysis,
      which revealed that the carrier rate of alpha-thal in Guizhou Province was 3.28%.
      One thousand and forty-five individuals referred to our hospital were tested for
      alpha-thal mutations. Two hundred and twenty-four cases were determined as alpha
      thal carriers or patients. A total of 11 genotypes and five different alpha-thal
      mutations were identified in these 224 cases. Of these mutations, more than 96.0%
      were deletions, including - -(SEA) (65.89%), -alpha(3.7) (rightward) (22.87%) and
      -alpha(4.2) (leftward) (7.74%). The other two nondeletional mutations, Hb
      Constant Spring (Hb CS, alpha(CS)alpha, HBA2: c.427T > C) and Hb Quong Sze [Hb
      QS, alpha(QS)alpha, HBA2: c.377T > C (or HBA1)] account for 2.71% and 0.78%,
      respectively. The results of this study will be useful in genetic counseling and
      prenatal diagnosis (PND) of alpha-thal in Guizhou Province. 

PMID- 26193977
TI  - Homozygosity for the AATAAA > AATA- - Polyadenylation Site Mutation on the alpha2
      Globin Gene Causing Transfusion-Dependent Hb H Disease in an Iranian Patient: A
      Case Report.
AB  - We describe a case of Hb H disease associated with homozygosity for a two
      nucleotide deletion in the polyadenylation signal of the alpha2-globin gene
      (HBA2: c.*93_*94delAA). The patient, a 27-year-old son of a consanguineous
      couple, needs regular blood transfusions every 6 months. 

PMID- 26193978
TI  - Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or
      rabeprazole 10 mg in healthy adult male subjects--a randomised open-label cross
      over study.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are widely used for the treatment of
      acid-related diseases. Vonoprazan is a member of a new class of acid
      suppressants; potassium-competitive acid blockers. Vonoprazan may thus be an
      alternative to PPIs. AIM: To evaluate efficacy, rapidity and duration of acid
      inhibitory effects of vonoprazan vs. two control PPIs, esomeprazole and
      rabeprazole, in 20 healthy Japanese adult male volunteers with CYP2C19 extensive
      metaboliser genotype. METHODS: In this randomised, open-label, two-period cross
      over study, vonoprazan 20 mg and esomeprazole 20 mg (Study V vs. E) or
      rabeprazole 10 mg (Study V vs. R) were orally administered daily for 7 days.
      Primary pharmacodynamic endpoint was gastric pH over 24 h measured as percentage
      of time pH >=3, >=4 and >=5 (pH holding time ratios; HTRs) and mean gastric pH.
      RESULTS: Acid-inhibitory effect (pH4 HTR) of vonoprazan was significantly greater
      than that of esomeprazole or rabeprazole on both Days 1 and 7; Day 7 difference
      in pH4 HTR for vonoprazan vs. esomeprazole was 24.6% [95% confidence interval
      (CI): 16.2-33.1] and for vonoprazan vs. rabeprazole 28.8% [95% CI: 17.2-40.4].
      The Day 1 to Day 7 ratio of 24-h pH4 HTRs was >0.8 for vonoprazan, compared with
      0.370 for esomeprazole and 0.393 for rabeprazole. Vonoprazan was generally well
      tolerated. One vonoprazan subject withdrew due to a rash which resolved after
      discontinuation. CONCLUSIONS: This study demonstrated a more rapid and sustained
      acid-inhibitory effect of vonoprazan 20 mg vs. esomeprazole 20 mg or rabeprazole
      10 mg. Therefore, vonoprazan may be a potentially new treatment for acid-related
      diseases.

PMID- 26193979
TI  - Cardiac malposition (ectopia cordis) in a cat.
AB  - OBJECTIVE: To describe a case of cardiac malposition in a cat, and the successful
      management of the anomaly. CASE DESCRIPTION: A 2-year-old male neutered male
      British Shorthair cat weighing 7.58 kg was referred for bicavitary effusion.
      Ultrasonography and echocardiography demonstrated displacement of the heart into
      the abdomen through a diaphragmatic defect. Clinical signs of right-sided
      congestive heart failure were attributed to mechanical restriction of diastolic
      function by a constrictive segment of fibrous pericardium and to impaired venous
      return due to a kink in the caudal vena cava. Surgical repositioning of the heart
      into the thoracic cavity and a subtotal pericardectomy were performed, and the
      diaphragmatic defect was repaired. The patient recovered well postoperatively.
      NEW OR UNIQUE INFORMATION PROVIDED: The diagnosis and management of cardiac
      malposition has not been previously described in cats. With timely diagnosis and
      surgical intervention, a favorable outcome is possible.

PMID- 26193980
TI  - Effects of fine-needle aspiration biopsy (FNAB) nodule depth on pain score.
AB  - PURPOSE: Fine-needle aspiration biopsy (FNAB) of the thyroid is generally a well
      tolerated procedure associated with weak levels of pain. However, pain may be
      very intense in some patients. The cause for the pain in these patients has not
      been identified. The hypothesis of this study is that there is a likely
      relationship between pain level and nodule depth during FNAB. MATERIALS AND
      METHODS: Included in the study were 98 patients with euthyroid nodular goiter who
      underwent FNAB. When ultrasound guided thyroid fine-needle aspiration biopsy was
      performed findings such as the distance of the nodule to the skin, the size of
      the nodule, visual analogue scale (VAS) score values were recorded. FINDINGS: The
      distance of nodule to skin and nodule size was measured, respectively, as 10.7 +/
      2.8 mm and 21.7 +/- 8.6 mm. Mean VAS score was 36 +/- 16. FNAB-related pain was
      correlated with the nodule depth (r = 0.43, p < 0.001). In the logistic
      regression analysis, we also found that high VAS score class was effected by only
      nodule depth (B = -1.619; OR 1.287; CI 1.057-1.565, p < 0.05). CONCLUSION: Our
      results show that pain increased significantly during FNAB in patients who had
      more deeply situated nodules. Local anesthetic methods may be recommended for
      these patients.

PMID- 26193981
TI  - Endoscopic transnasal approach to medial orbital lesions.
AB  - OBJECTIVE: This case report presents our experience of endoscopic transnasal
      management of medial intra- and extraconal lesions. CASE REPORT: An endoscopic
      transnasal approach to intra-orbital lesions was used for nine patients. Four
      patients had intraconal lesions and five had lesions in the extraconal space.
      Post-operatively, seven patients reported an improvement in visual acuity and two
      reported stable vision. There were no complications of cerebrospinal leakage or
      diplopia. CONCLUSION: This case series demonstrated the safety and effectiveness
      of an endoscopic transnasal approach to managing intraconal and extraconal
      lesions. This minimally invasive technique should be considered a valid
      alternative for accessing orbital tumours, particularly those located in the
      medial compartment.

PMID- 26193982
TI  - Hilbert-Huang Transformation Based Analyses of FP1, FP2, and Fz
      Electroencephalogram Signals in Alcoholism.
AB  - Chronic alcoholism may damage the central nervous system, causing imbalance in
      the excitation-inhibition homeostasis in the cortex, which may lead to hyper
      arousal of the central nervous system, and impairments in cognitive function. In
      this paper, we use the Hilbert-Huang transformation (HHT) method to analyze the
      electroencephalogram (EEG) signals from control and alcoholic observers who
      watched two different pictures. We examined the intrinsic mode function (IMF)
      based energy distribution features of FP1, FP2, and Fz EEG signals in the time
      and frequency domains for alcoholics. The HHT-based characteristics of the IMFs,
      the instantaneous frequencies, and the time-frequency-energy distributions of the
      IMFs of the clinical FP1, FP2, and Fz EEG signals recorded from normal and
      alcoholic observers who watched two different pictures were analyzed. We observed
      that the number of peak amplitudes of the alcoholic subjects is larger than that
      of the control. In addition, the Pearson correlation coefficients of the IMFs,
      and the energy-IMF distributions of the clinical FP1, FP2, and Fz EEG signals
      recorded from normal and alcoholic observers were analyzed. The analysis results
      show that the energy ratios of IMF4, IMF5, and IMF7 waves of the normal observers
      to the refereed total energy were larger than 10 %, respectively. In addition,
      the energy ratios of IMF3, IMF4, and IMF5 waves of the alcoholic observers to the
      refereed total energy were larger than 10 %. The FP1 and FP2 waves of the normal
      observers, the FP1 and FP2 waves of the alcoholic observers, and the FP1 and Fz
      waves of the alcoholic observers demonstrated extremely high correlations. On the
      other hand, the FP1 waves of the normal and alcoholic observers, the FP1 wave of
      the normal observer and the FP2 wave of the alcoholic observer, the FP1 wave of
      the normal observer and the Fz wave of the alcoholic observer, the FP2 waves of
      the normal and alcoholic FP2 observers, and the FP2 wave of the normal observer
      and the Fz wave of the alcoholic observer demonstrated extremely low
      correlations. The IMF4 of the FP1 and FP2 signals of the normal observer, and the
      IMF5 of the FP1 and FP2 signals of the alcoholic observer were correlated. The
      IMF4 of the FP1 signal of the normal observer and that of the FP2 signal of the
      alcoholic observer as well as the IMF5 of the FP1 signal of the normal observer
      and that of the FP2 signal of the alcoholic observer exhibited extremely low
      correlations. In this manner, our experiment leads to a better understanding of
      the HHT-based IMFs features of FP1, FP2, and Fz EEG signals in alcoholism. The
      analysis results show that the energy ratios of the wave of an alcoholic observer
      to its refereed total energy for IMF4, and IMF5 in the delta band for FP1, FP2,
      and Fz channels were larger than those of the respective waves of the normal
      observer. The alcoholic EEG signals constitute more than 1 % of the total energy
      in the delta wave, and the reaction times were 0_4, 4_8, 8_12, and 12_16 s. For
      normal EEG signals, more than 1 % of the total energy is distributed in the delta
      wave, with a reaction time 0 to 4 s. We observed that the alcoholic subject
      reaction times were slower than those of the normal subjects, and the alcoholic
      subjects could have experienced a cognitive error. This phenomenon is due to the
      intoxicated central nervous systems of the alcoholic subjects.

PMID- 26193983
TI  - Role of autologous platelet-rich plasma in treatment of long-bone nonunions: a
      prospective study.
AB  - PURPOSE: Fracture union is a complex biological process, which depends upon
      several systemic and local factors. Disturbance of any of these factors may lead
      to nonunion of the fracture. These nonunions have a huge impact on quality of
      life as well as socioeconomical aspects. The platelets on activation release a
      number of growth factors and differentiation factors, which play important role
      in fracture healing. This study aimed to look for efficacy of platelet-rich
      plasma in the treatment of established fracture nonunions of long bones. METHODS:
      A total of 94 patients with established nonunion of long bone (35 tibia, 30
      femur, 11 humerus, 4 radius, 12 ulna, 2 with both radius and ulna) were included
      in this study. We injected 15-20 ml of autologous platelet-rich plasma
      (>2,000,000 platelets/MUl) under image intensifier at each nonunion site. The
      fracture union was evaluated clinically and radiologically regularly at monthly
      interval till 4 months. RESULTS: Eighty-two patients had their fracture united at
      the end of 4 months. Thirty-four patients showed bridging trabeculae on X-rays at
      the end of 2 months, while 41 patients showed bridging trabeculae at the end of
      third month. Twelve patients did not show any attempt of union at 4 months and
      were labeled as failure of treatment. There were no complications. CONCLUSION:
      Platelet-rich plasma is a safe and effective treatment for the treatment of
      nonunions. More studies are needed to look into molecular mechanism of this
      fracture healing acceleration by platelet-rich plasma.

PMID- 26193984
TI  - Patients with brain metastases derived from gastrointestinal cancer: clinical
      characteristics and prognostic factors.
AB  - PURPOSE: This study seeks to evaluate the natural history, outcome, and possible
      prognostic factors in patients with brain metastases derived from
      gastrointestinal cancers. METHODS: The clinical features, prognostic factors, and
      the effects of different treatment modalities on survival were retrospectively
      investigated in 103 patients with brain metastases derived from gastrointestinal
      cancers. RESULTS: The median time from diagnosis of primary tumor to brain
      metastasis was 22.00 months. The interval between diagnosis of primary tumor
      relapse and brain metastasis was 8.00 months. The median follow-up time was 7.80
      months. The median survival time after diagnosis of brain metastases was 4.10
      months for all patients and 1.17 months for patients who received only steroids
      (36.9 %), 3.97 months for patients who only received whole-brain radiation
      therapy (WBRT 31.1 %), 11.07 months for patients who received gamma-knife surgery
      alone or/and WBRT (20.4 %), and 13.70 months for patients who underwent surgery
      and radiotherapy (12 patients, 11.6 %) (P < 0.001). Multivariate analysis
      revealed that recursive partitioning analysis (RPA) class, extracranial
      metastasis, and chemotherapy were independent prognostic factors. Brain
      metastasis derived from gastrointestinal tract cancer is rare, and overall
      patient survival is poor. CONCLUSION: RPA class, chemotherapy after brain
      metastases, and treatment regimens were independent prognostic factors for the
      survival of patients with brain metastases derived from gastrointestinal cancers.

PMID- 26193985
TI  - The relationship between polymorphisms of genes regulating DNA repair or cell
      division and the toxicity of platinum and vinorelbine chemotherapy in advanced
      NSCLC patients.
AB  - INTRODUCTION: Platinum-based chemotherapy and 3rd generation drugs is still the
      main treatment option for advanced non-small cell lung cancer (NSCLC) patients
      without activating EGFR mutations or ALK rearrangements. However, the side
      effects associated with cytostatics are well known. Changes in the genes (e.g.
      single nucleotide polymorphisms, SNPs) encoding proteins regulating DNA repair or
      cell division could potentially influence on both the susceptibility of cancer
      cells to chemotherapy, and the occurrence of toxicities. MATERIALS AND METHODS:
      In presented study, the relationship between the fourteen SNPs in nine DNA repair
      and cell division regulating genes: ERCC1, XPD, XPA, XPC, XRCC1, XPG, RRM1,
      BRCA1, STMN1 and the toxicity of first-line chemotherapy in NSCLC patients were
      investigated. SNPs were determined by SNaPshot PCR(r) in DNA isolated from
      peripheral blood of 55 NSCLC patients treated with platinum compound and
      vinorelbine. The toxicity of therapy was evaluated according to the Common
      Toxicity Criteria (CTC) Version 4.03. RESULTS: The odds ratio (OR) of severe
      haematological toxicity was significantly lower in carriers of the T allele of
      XRCC1 gene (1196A > G, OR = 0.22, 95 % CI: 0.06-0.82, p = 0.018) and higher in
      the carriers of the T allele (2704C > A) of XPC gene (OR: 7.50, 95 % CI: 0.89
      63.17, p = 0.036) compared to the remaining patients. Risk of severe
      hepatotoxicity was significantly lower in carriers of the C allele of STMN1 (
      2166T > C, OR = 0.09, 95 % CI: 0.01-1.12, p = 0.025) than in patients with T
      allele of this gene. In carriers of G allele (2251A > C, OR: 0.24, 95 % CI: 0.07
      0.81, p = 0.017) and T (934G > A, OR: 0.26, 95 % CI: 0.07-0.90, p = 0.029) of XPD
      gene, risk of severe nephrotoxicity was significantly lower than in other
      patients. CONCLUSIONS: Selected SNPs of genes encoding DNA repair enzymes and
      cell division regulation proteins could be useful biomarkers for prediction of
      platinum and vinorelbine-based chemotherapy toxicity in patients with advanced
      NSCLC.

PMID- 26193986
TI  - Are the motor features of verb meanings represented in the precentral motor
      cortices? Yes, but within the context of a flexible, multilevel architecture for
      conceptual knowledge.
AB  - One of the most controversial issues in the cognitive neuroscience literature on
      concepts is whether the motor features of verb meanings are represented in the
      precentral motor cortices. Much of this debate stems from the fact that the
      empirical data are mixed with regard to (1) whether action verbs engage the
      precentral motor cortices in the predicted ways, (2) whether that engagement is
      automatic, and (3) whether it is essential for comprehension. I argue that the
      available data can best be accommodated by theoretical models which assume that
      conceptual knowledge is underpinned by a flexible, multilevel architecture that
      includes not only low-level modality-specific systems for perception, action, and
      emotion, but also high-level cross-modal convergence/divergence zones, as well as
      the statistical co-occurrence patterns of word-forms across discourses. From the
      perspective of such pluralistic approaches, the motor features of verb meanings
      are indeed represented in the precentral motor cortices, but their retrieval is
      modulated by task and context and is not always necessary for word comprehension.

PMID- 26193987
TI  - Influence of infusion method on gemcitabine pharmacokinetics: a controlled
      randomized multicenter trial.
AB  - PURPOSE: Ensuring the correct administration of antineoplastic drugs is a
      constantly challenging task. Nowadays, several specific infusion devices have
      been marketed to decrease occupational exposure to these drugs through a post
      administration rinsing step. As their impact on drug pharmacokinetics has never
      been evaluated, the objective of this study was to assess how the infusion
      process may alter the pharmacokinetics of antineoplastic drugs. METHODS: We
      developed a prospective randomized multicenter pharmacokinetic study (ONCOPERF01)
      to compare the influence of three infusion techniques (gravity-fed infusion-GFI,
      infusion pump-IP, and gravity-fed infusion with post-administration rinsing-PAR)
      to assess the impact of both flow rate and post-administration rinsing on
      gemcitabine pharmacokinetics during three consecutive administrations.
      Gemcitabine pharmacokinetics was determined with a two-compartment model after
      plasma dosing with an HPLC-UV method. Statistical comparisons of the three groups
      were made using repeated-measure analysis of variance (PROC MIXED). RESULTS:
      Patients received gemcitabine by gravity-fed infusion (GFI, n = 9; IP, n = 9;
      PAR, n = 7). Significant differences were noted between infusion duration (GFI =
      30.0 +/- 2.6 min, IP = 29.1 +/- 1.2 min, PAR = 33.7 +/- 3.5 min; p = 0.003) and
      AUCt (GFI = 23.5 +/- 8.2 uM h, IP = 25.4 +/- 9.1 uM h, PAR = 28.5 +/- 6.3 uM h; p
      = 0.0009), which was significantly higher in the infusion group with post
      administration rinsing than in the other groups. CONCLUSIONS: The ONCOPERF01
      study indicates that post-administration rinsing leads to a significant increase
      in patient exposure to gemcitabine, whereas controlling flow rate has no
      significance. Further surveys are required to assess the impact of such infusion
      techniques on other antineoplastic drugs.

PMID- 26193988
TI  - Characterization of the metabolism of benzaldehyde dimethane sulfonate (NSC
      281612, DMS612).
AB  - INTRODUCTION: Benzaldehyde dimethane sulfonate (BEN, DMS612, NSC281612) is a
      bifunctional alkylating agent currently in clinical trials. We previously
      characterized the degradation products of BEN in plasma and blood. The conversion
      of BEN to its carboxylic acid analogue (BA) in whole blood, but not plasma,
      suggests that an enzyme in RBCs may be responsible for this conversion. BEN
      conversion to BA was observed in renal carcinoma cells and appeared to correlate
      with IC50. To better understand the pharmacology of BEN, we aimed to evaluate the
      metabolism and enzymes potentially responsible for the conversion of BEN to BA.
      METHODS: Human red blood cells (RBC) were used to characterize kinetics and
      susceptibility to enzyme-specific inhibitors. Recombinant enzymes were used to
      confirm metabolism of BEN to BA. Analytes were quantitated with established LC
      MS/MS methods. RESULTS: Average apparent Vmax and Km were 68 ng/mL min(-1) [10%
      RBC](-1) and 373 ng/mL, respectively. The conversion of BEN to BA in RBC was not
      inhibited by carbon monoxide, nitrogen gas, or menadione, an inhibitor of
      aldehyde oxidase. The conversion was inhibited by disulfiram, an inhibitor of
      ALDH. Of available ALDH isoforms ALDH1A1, ALDH3A1, ALDH2, and ALDH5A1, only
      ALDH1A1 converted BEN to BA. CONCLUSION: The activating conversion of BEN to BA
      is mediated not by CYP450 enzymes or aldehyde oxidase, but by ALDH1A1. This
      enzyme, a potential stem cell marker, may be a candidate biomarker for clinical
      activity of BEN.

PMID- 26193989
TI  - Assessment and management of pain in children and adolescents with bleeding
      disorders: a cross-sectional study from three haemophilia centres.
AB  - INTRODUCTION: Pain is a major clinical problem in patients with bleeding
      disorders. This study aimed to determine the level of pain and how it is managed
      in children and adolescents with bleeding disorders. METHODS: This cross
      sectional study was performed in three haemophilia centres (one in Shiraz and two
      in London).The data were collected using questions about pain management and Wong
      Baker Faces Pain Rating Scale at routine clinical review as well as attendance
      for bleed treatment in summer 2014. RESULTS: This study indicated no difference
      among the three haemophilia centres regarding having pain, however, a significant
      difference was found among them concerning the mean score of pain intensity.
      Among the 154 subjects, 20.8% had pain on the study day, most reporting moderate
      levels of pain. The study participant's most frequently described their pain as
      aching, dull, throbbing and stabbing. Moreover, 84.38% of pain was experienced in
      joints and the most common painful joints were knees, ankles, elbows, hands and
      hips. The most common pain relief strategies included factor administration,
      immobilization and rest, ice packs and analgesia. Pain was significantly
      associated with disease severity and age. CONCLUSION: As the intensity of pain in
      on-demand patients was highest, using prophylaxis treatment is suggested.
      Moreover, adolescent patients reported more pain; giving more self-care
      information to them and their parents is recommended. Since little evidence was
      published for pain assessment and management in children and adolescents with
      bleeding disorders, more research is recommended.

PMID- 26193990
TI  - Antimicrobial-resistant and ESBL-producing Escherichia coli in different
      ecological niches in Bangladesh.
AB  - INTRODUCTION: The rapid and wide-scale environmental spread of multidrug
      resistant bacteria in different ecosystems has become a serious issue in recent
      years. OBJECTIVES: To investigate the epidemiology of antimicrobial resistance
      and extended spectrum beta-lactamase (ESBL) in Bangladeshi wild birds and aquatic
      environments, samples were taken from Open Bill Stork (Anastomus oscitans) (OBS)
      and the nearby water sources. METHODS: Water and fresh fecal samples were
      collected from several locations. All samples were processed and cultured for
      Escherichia coli and tested for antibiotic susceptibility against commonly used
      antibiotics. ESBL producers were characterized at genotypic level using
      polymerase chain reaction (PCR), sequencing, multilocus sequence typing, and rep
      PCR. RESULTS AND DISCUSSION: A total of 76 E. coli isolates from the 170 OBS and
      8 E. coli isolates from three river sources were isolated. In total, 29% of E.
      coli isolated from OBS and all of the E. coli isolated from water sources were
      resistant to at least one of the tested antimicrobials. Resistant phenotypes were
      observed with all antimicrobials except tigecycline, gentamicin, imipenem, and
      chloramphenicol. Multidrug resistance was observed in 2.6% of OBS and 37.5% of
      the water isolates. Also, 1.2% of the ESBL-producing E. coli were isolated from
      OBS, whereas 50% of the E. coli isolated from water sources were ESBL producers
      possessing the CTX-M-15 gene. The most concerning aspect of our findings was the
      presence of human-associated E. coli sequence types in the water samples, for
      example, ST156-complex156, ST10-complex10 and ST46. CONCLUSION: This study
      reports the presence of multidrug-resistant ESBL-producing E. coli in OBSs and
      nearby aquatic sources in Bangladesh.

PMID- 26193991
TI  - A novel substitution -sensing for hydroquinone and catechol based on a poly(3
      aminophenylboronic acid)/MWCNTs modified electrode.
AB  - A facile electrochemical sensor for hydroquinone (HQ) and catechol (CC)
      determination was successfully fabricated by the modification of poly(3
      aminophenylboronic acid) (pAPBA) film and multi-walled carbon nanotubes (MWCNTs)
      on a glassy carbon electrode (pAPBA/MWCNTs/GCE). The prepared sensor was
      characterized by scanning electron microscope and electrochemical impedance
      spectroscopy. Under optimal conditions, differential pulse voltammetry was
      employed to quantify individual HQ and CC within the concentration range of 5.0 *
      10(-7)-4.0 * 10(-5) mol L(-1) and 7.0 * 10(-6)-1.0 * 10(-4) mol L(-1),
      respectively. Based on the covalent binding between the boronic acid groups of
      pAPBA film and the cis-diol-containing molecule, a novel substitution-sensing
      strategy was proposed for the highly sensitive determination of CC. With the
      addition of CC into HQ solution, covalent interaction between CC and APBA
      occurred and the HQ was displaced by CC, resulting in a decrease of HQ oxidation
      peak current and the increase of the CC oxidation peak current. The summation of
      both current changes (Delta|IHQ| + Delta|ICC|) were combined for CC sensitive
      detection in a concentration range of 4.0 * 10(-8)-1.7 * 10(-5) mol L(-1) with a
      limit of detection of 4.3 * 10(-9) mol L(-1). The sensor was successfully applied
      to the determination of CC in spiked water samples. 

PMID- 26193992
TI  - Highly efficient and selective photocatalytic reduction of nitroarenes using the
      Ni2P/CdS catalyst under visible-light irradiation.
AB  - A highly efficient and selective heterogeneous photocatalytic system for nitro
      reduction to amino organics was established using CdS, Ni2P and Na2S/Na2SO3 as a
      photosensitizer, a cocatalyst and a sacrificial electron donor in aqueous
      solution, respectively. Two competing pathways for photocatalytic H2 production
      and nitro reduction were found. Also, the reduction of nitroarenes to aniline was
      confirmed to proceed through both the direct and condensation routes. 

PMID- 26193993
TI  - Role of gold nanoparticles as drug delivery vehicles for chondroitin sulfate in
      the treatment of osteoarthritis.
AB  - Osteoarthritis is a disease which is characterized by joint pain, swelling and
      stiffness. Articular cartilage has limited self-repair capacity due to its
      avascular and aneural nature. In this work, we show the use of gold nanoparticles
      (AuNps) for enhancing the delivery of chondroitin sulfate (CS), a drug used in
      the treatment of osteoarthritis (OA). AuNps were synthesized and were
      characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV
      Vis) spectroscopy, Fourier transform infrared spectroscopy (FTIR), and X-Ray
      diffraction analysis. AuNps were combined with CS (AuNps-CS) and their effect on
      primary goat chondrocytes was studied using MTT assay, Hoechst staining,
      production of glycosaminoglycan and collagen. Cell viability studies by MTT
      revealed that AuNps-CS stimulate cell proliferation. A two-fold increase in GAG
      and collagen production was observed in presence of AuNps-CS combination as
      compared to native CS, indicating that this combination stimulates chondrocyte
      proliferation and enhances extracellular matrix production (ECM). Hence, this
      study exhibits the potential of AuNps as a carrier of CS for treatment of
      osteoarthritis.

PMID- 26193994
TI  - A unified diabatic description for electron transfer reactions, isomerization
      reactions, proton transfer reactions, and aromaticity.
AB  - While diabatic approaches are ubiquitous for the understanding of electron
      transfer reactions and have been mooted as being of general relevance, alternate
      applications have not been able to unify the same wide range of observed
      spectroscopic and kinetic properties. The cause of this is identified as the
      fundamentally different orbital configurations involved: charge-transfer
      phenomena involve typically either 1 or 3 electrons in two orbitals whereas most
      reactions are typically closed shell. As a result, two vibrationally coupled
      electronic states depict charge-transfer scenarios whereas three coupled states
      arise for closed-shell reactions of non-degenerate molecules and seven states for
      the reactions implicated in the aromaticity of benzene. Previous diabatic
      treatments of closed-shell processes have considered only two arbitrarily chosen
      states as being critical, mapping these states to those for electron transfer. We
      show that such effective two-state diabatic models are feasible but involve
      renormalized electronic coupling and vibrational coupling parameters, with this
      renormalization being property dependent. With this caveat, diabatic models are
      shown to provide excellent descriptions of the spectroscopy and kinetics of the
      ammonia inversion reaction, proton transfer in N2H7(+), and aromaticity in
      benzene. This allows for the development of a single simple theory that can semi
      quantitatively describe all of these chemical phenomena, as well as of course
      electron-transfer reactions. It forms a basis for understanding many
      technologically relevant aspects of chemical reactions, condensed-matter physics,
      chemical quantum entanglement, nanotechnology, and natural or artificial solar
      energy capture and conversion. 

PMID- 26193995
TI  - Hirshfeld-based intrinsic polarizability density representations as a tool to
      analyze molecular polarizability.
AB  - In this work, a general scheme to visualize polarizability density distributions
      is proposed and implemented in a Hirshfeld-based partitioning scheme. This allows
      us to obtain easy-to-interpret pictorial representations of both total and
      intrinsic polarizabilities where each point of the density is formed by the
      contribution of any atom or group of atoms in the molecule. In addition, the
      procedure used here permits the possibility of removing the size dependence of
      the electric-dipole polarizability. Such a development opens new horizons in
      exploring new applications for the analysis of the molecular polarizability
      tensor. For instance, this visualization shows which atoms or regions are more
      polarizable distinguishing, moreover, the fine structure of atoms affected by the
      vicinity, and might extend the dipole polarizability as a tool for aromaticity
      studies in polycyclic aromatic hydrocarbons. Additionally, this approach can
      serve us to assess the methods performance in describing the interaction of
      electric fields with a molecule and local electron correlation effects in
      intrinsic polarizabilities.

PMID- 26193996
TI  - Structurally Diverse Polyamines: Solid-Phase Synthesis and Interaction with DNA.
AB  - A versatile solid-phase approach based on peptide chemistry was used to construct
      four classes of structurally diverse polyamines with modified backbones: linear,
      partially constrained, branched, and cyclic. Their effects on DNA duplex
      stability and structure were examined. The polyamines showed distinct activities,
      thus highlighting the importance of polyamine backbone structure. Interestingly,
      the rank order of polyamine ability for DNA compaction was different to that for
      their effects on circular dichroism and melting temperature, thus indicating that
      these polyamines have distinct effects on secondary and higher-order structures
      of DNA. 

PMID- 26193997
TI  - Comparative finite element analysis of the cranial performance of four
      herbivorous marsupials.
AB  - Marsupial herbivores exhibit a wide variety of skull shapes and sizes to exploit
      different ecological niches. Several studies on teeth, dentaries, and jaw
      adductor muscles indicate that marsupial herbivores exhibit different
      specializations for grazing and browsing. No studies, however, have examined the
      skulls of marsupial herbivores to determine the relationship between stress and
      strain, and the evolution of skull shape. The relationship between skull
      morphology, biomechanical performance, and diet was tested by applying the finite
      element method to the skulls of four marsupial herbivores: the common wombat
      (Vombatus ursinus), koala (Phascolarctos cinereus), swamp wallaby (Wallabia
      bicolor), and red kangaroo (Macropus rufus). It was hypothesized that grazers,
      requiring stronger skulls to process tougher food, would have higher
      biomechanical performance than browsers. This was true when comparing the koala
      and wallaby (browsers) to the wombat (a grazer). The cranial model of the wombat
      resulted in low stress and high mechanical efficiency in relation to a robust
      skull capable of generating high bite forces. However, the kangaroo, also a
      grazer, has evolved a very different strategy to process tough food. The cranium
      is much more gracile and has higher stress and lower mechanical efficiency, but
      they adopt a different method of processing food by having a curved tooth row to
      concentrate force in a smaller area and molar progression to remove worn teeth
      from the tooth row. Therefore, the position of the bite is crucial for the
      structural performance of the kangaroo skull, while it is not for the wombat
      which process food along the entire tooth row. In accordance with previous
      studies, the results from this study show the mammalian skull is optimized to
      resist forces generated during feeding. However, other factors, including the
      lifestyle of the animal and its environment, also affect selection for skull
      morphology to meet multiple functional demands.

PMID- 26193998
TI  - An Increased Risk of Second Malignant Neoplasms After Rhabdomyosarcoma:
      Population-Based Evidence for a Cancer Predisposition Syndrome?
AB  - BACKGROUND: Rhabdomyosarcoma survivors have an increased risk of developing
      second malignant neoplasms (SMN); this risk is traditionally attributed to the
      effects of multidisciplinary management required for cure. However, the impact of
      constitutional predisposition has not been properly analyzed. METHODS: We
      analyzed the risk of SMN among 1,151 children diagnosed with rhabdomyosarcoma and
      reported to the Surveillance, Epidemiology, and End Results registries (SEER-9)
      from 1973 to 2010. Standardized incidence ratios (SIR) and corresponding 95%
      confidence intervals (CI) were calculated using SEERStat 8.1.2. RESULTS: Children
      with pleomorphic and embryonal rhabdomyosarcoma had an increased risk of
      developing a SMN (SIR = 15.77, 95%CI 1.91-56.96 and SIR = 5.6, 95%CI 3.32-8.85,
      respectively). The risk was age-dependent; the highest was among children <2
      years (SIR = 13.38, 95%CI 4.34-31.22) and the lowest was in children >10 years
      (SIR = 3.35, 95%CI 1.53-6.35). The risk for the youngest patients was higher for
      those with embryonal rhabdomyosarcoma (SIR = 14.72, 95%CI 4.01-37.70) compared to
      other histiotypes. Additionally, the risk of SMN was independent of the use of
      radiation to the primary (SIR = 6.50, 95%CI 3.97-10.03 and SIR = 4.57, 95%CI 2.09
      8.68, for children receiving and not receiving radiation, respectively). The
      pattern of SMN observed was consistent with the Li-Fraumeni spectrum.
      CONCLUSIONS: Children with rhabdomyosarcoma are at high risk of developing SMN.
      This risk is higher for a subgroup of young children with pleomorphic and
      embryonal histologies, and is independent of the use of radiation. This suggests
      that a subgroup of children with pleomorphic and embryonal rhabdomyosarcoma may
      have a constitutional cancer predisposition.

PMID- 26193999
TI  - Complex karyotype is a stronger predictor than del(17p) for an inferior outcome
      in relapsed or refractory chronic lymphocytic leukemia patients treated with
      ibrutinib-based regimens.
AB  - BACKGROUND: Ibrutinib is active in patients with relapsed/refractory (R/R)
      chronic lymphocytic leukemia (CLL). In patients treated with ibrutinib for R/R
      CLL, del(17p), identified by interphase fluorescence in situ hybridization
      (FISH), is associated with inferior progression-free survival despite equivalent
      initial response rates. Del(17p) is frequently associated with a complex
      metaphase karyotype (CKT); the prognostic significance of CKT in ibrutinib
      treated patients has not been reported. METHODS: This study reviewed 88 patients
      treated for R/R CLL at The University of Texas MD Anderson Cancer Center with
      investigational ibrutinib-based regimens from 2010 to 2013. Pretreatment FISH and
      lipopolysaccharide-stimulated metaphase cytogenetic analysis were performed on
      bone marrow. RESULTS: An adequate pretreatment metaphase karyotype was available
      for 56 of the 88 patients. The karyotype was complex in 21 of the 56 cases; 17 of
      the 21 had del(17p) according to FISH. The overall response rate, including
      partial remission with persistent lymphocytosis, was 94%; 18% had complete
      responses. In a multivariate analysis (MVA), only CKT was significantly
      associated with event-free survival (EFS; hazard ratio [HR], 6.6 [95% CI 1.7
      25.6]; P = .006). Fludarabine-refractory CLL (HR, 6.9 [95% CI 1.8-27.1], P =
      .005) and CKT (HR 5.9 [95% CI 1.6-22.2], P = .008) were independently associated
      with inferior overall survival (OS) in MVA. Del(17p) by FISH was not
      significantly associated with EFS or OS in MVA. CONCLUSIONS: CKT is a powerful
      predictor of outcomes for ibrutinib-treated patients with R/R CLL and may be a
      stronger predictor of biological behavior than del(17p) by FISH. Because of their
      relatively poor outcomes, patients with CKT are ideal candidates for studies of
      consolidative treatment strategies or novel treatment combinations.

PMID- 26194000
TI  - Hexahedron Prism-Anchored Octahedronal CeO2: Crystal Facet-Based Homojunction
      Promoting Efficient Solar Fuel Synthesis.
AB  - An unprecedented, crystal facet-based CeO2 homojunction consisting of hexahedron
      prism-anchored octahedron with exposed prism surface of {100} facets and
      octahedron surface of {111} facets was fabricated through solution-based
      crystallographic-oriented epitaxial growth. The photocatalysis experiment reveals
      that growth of the prism arm on octahedron allows to activate inert CeO2
      octahedron for an increase in phototocatalytic reduction of CO2 into methane. The
      pronounced photocatalytic performance is attributed to a synergistic effect of
      the following three factors: (1) band alignment of the {100} and {111} drives
      electrons and holes to octahedron and prism surfaces, respectively, aiming to
      reach the most stable energy configuration and leading to a spatial charge
      separation for long duration; (2) crystallographic-oriented epitaxial growth of
      the CeO2 hexahedron prism arm on the octahedron verified by the interfacial
      lattice fringe provides convenient and fast channels for the photogenerated
      carrier transportation between two units of homojuntion; (3) different effective
      mass of electrons and holes on {100} and {111} faces leads to high charge carrier
      mobility, more facilitating the charge separation. The proposed facet-based
      homojunction in this work may provide a new concept for the efficient separation
      and fast transfer of photoinduced charge carriers and enhancement of the
      photocatalytic performance. 

PMID- 26194002
TI  - Erratum: From link-prediction in brain connectomes and protein interactomes to
      the local-community-paradigm in complex networks.

PMID- 26194003
TI  - Analysis of context factors in compulsory and incentive strategies for improving
      attraction and retention of health workers in rural and remote areas: a
      systematic review.
AB  - BACKGROUND: Current literature systematically reports that interventions to
      attract and retain health workers in underserved areas need to be context
      specific but rarely defines what that means. In this systematic review, we try to
      summarize and analyse context factors influencing the implementation of
      interventions to attract and retain rural health workers. METHODS: We searched
      online databases, relevant websites and reference lists of selected literature to
      identify studies on compulsory rural service programmes and financial incentives.
      Forty studies were selected. Information regarding context factors at macro, meso
      and micro levels was extracted and synthesized. RESULTS: Macro-level context
      factors include political, economic and social factors. Meso-level factors
      include health system factors such as maldistribution of health workers, growing
      private sector, decentralization and health financing. Micro-level factors refer
      to the policy implementation process including funding sources, administrative
      agency, legislation process, monitoring and evaluation. CONCLUSIONS: Macro-, meso
      and micro-level context factors can play different roles in agenda setting,
      policy formulation and implementation of health interventions to attract and
      retain rural health workers. These factors should be systematically considered in
      the different stages of policy process and evaluation.

PMID- 26194004
TI  - Increasing trend of fluconazole-non-susceptible Cryptococcus neoformans in
      patients with invasive cryptococcosis: a 12-year longitudinal study.
AB  - BACKGROUND: This study aimed to investigate the rate of fluconazole-non
      susceptible Cryptococcus neoformans in Southern Taiwan for the period 2001-2012
      and analyze the risk factors for acquiring it among patients with invasive
      cryptococcosis. METHODS: All enrolled strains were isolated from blood or
      cerebrospinal fluid samples of the included patients. If a patient had multiple
      positive results for C. neoformans, only the first instance was enrolled.
      Susceptibility testing was performed using the Clinical and Laboratory Standards
      Institutes M27-A3 broth micro-dilution method. The MIC interpretative criteria
      for susceptibility to fluconazole were <= 8 MUg/ml. A total of 89 patients were
      included. Patients (n = 59) infected by fluconazole-susceptible strains were
      compared with those (n = 30) infected by non-susceptible strains. The patients'
      demographic and clinical characteristics were analyzed. RESULTS: The rate of
      fluconazole-non-susceptible C. neoformans in the study period significantly
      increased over time (p < 0.001). The C. neoformans isolated in 2011-2012 (odds
      ratio: 10.68; 95 % confidence interval: 2.87-39.74; p < 0.001) was an independent
      predictive factor for the acquisition of fluconazole-non-susceptible C.
      neoformans. CONCLUSIONS: The rate of fluconazole-non-susceptible C. neoformans
      has significantly increased recently. Continuous and large-scale anti-fungal
      susceptibility tests for C. neoformans are warranted to confirm this trend.

PMID- 26194005
TI  - Research advances in microneme protein 3 of Toxoplasma gondii.
AB  - Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite. It
      has extensive host populations and is prevalent globally; T. gondii infection can
      cause a zoonotic parasitic disease. Microneme protein 3 (MIC3) is a secreted
      protein that is expressed in all stages of the T. gondii life cycle. It has
      strong immunoreactivity and plays an important role in the recognition, adhesion
      and invasion of host cells by T. gondii. This article reviews the molecular
      structure of MIC3, its role in the invasion of host cells by parasites, its
      relationship with parasite virulence, and its induction of immune protection to
      lay a solid foundation for an in-depth study of potential diagnostic agents and
      vaccines for preventing toxoplasmosis. 

PMID- 26194006
TI  - Barbed Roman blinds technique for the treatment of obstructive sleep apnea: how
      we do it?
AB  - Retro-palatal obstruction is often involved in the pathogenesis of obstructive
      sleep apnea syndrome (OSAS), which is currently treated by means of various
      surgical procedures. The aim of this paper is to describe our preliminary results
      using a new, minimally invasive and non-resective procedure called the "barbed
      Roman blinds technique" (BRBT), which was used to treat severe OSAS due to retro
      palatal obstruction. The apnea-hypopnea index (AHI), time with <90 % O2
      saturation, and Epworth Sleepiness Scale (ESS) of 32 consecutive adult
      outpatients (mean age 47.3 +/- 8.6 years) were compared before and after surgery.
      The tolerability of the procedure was assessed using a 0-10 visual analog scale
      (VAS). All of the treated patients experienced a clinical and subjective
      improvement as documented by the significant differences (P < 0.001) in their pre
      and post-BRBT AHI, time with <90 % O2 saturation, and ESS scores. There were no
      minor or major adverse events, and the good tolerability of the procedure was
      documented by the short mean hospital stay (1.2 +/- 0.5 days) and the mean VAS
      value of 4.3 +/- 0.7. The mean follow-up period was 12.2 +/- 2.0 months. The
      preliminary results indicate that the BRBT is safe and effective, but long-term
      follow-up and comparative studies of larger case series are needed to confirm
      these encouraging findings.

PMID- 26194007
TI  - Impact of opportunistic testing in a systematic cervical cancer screening
      program: a nationwide registry study.
AB  - BACKGROUND: Systematic screening for precancerous cervical lesions has resulted
      in decreased incidence and mortality of cervical cancer. However, even in
      systematic screening programs, many women are still tested opportunistically.
      This study aimed to determine the spread of opportunistic testing in a systematic
      cervical cancer screening program, the impact of opportunistic testing in terms
      of detecting cytological abnormalities and examine the associations between
      sociodemography and opportunistic testing. METHODS: A nationwide registry study
      was undertaken including women aged 23-49 years (n = 807,624) with a cervical
      cytology between 2010 and 2013. The women were categorised into: 1) screening
      after invitation; 2) routine opportunistic testing, if they were either tested
      more than 9 months after the latest invitation or between 2.5 years and 3 years
      after the latest cervical cytology and 3) sporadic opportunistic testing, if they
      were tested less than 2.5 years after the latest cervical cytology. Cytological
      diagnoses of women in each of the categories were identified and prevalence
      proportion differences (PPD) and 95% confidence intervals (CIs) were used to
      explore group differences. Associations between sociodemography and undergoing
      opportunistic testing were established by multinomial logistic regression.
      RESULTS: In total, 28.8% of the cervical cytologies were due to either routine
      (20.7%) or sporadic (8.1%) opportunistic testing. Among women undergoing routine
      opportunistic testing, a larger proportion had high-grade squamous
      intraepithelial abnormalities than invited women (PPD: 0.6%, 95 % CI: 0.03
      1.17%). A similar proportion of cytological abnormalities among women undergoing
      sporadic opportunistic testing and invited women was found. In multivariate
      analyses, younger age, being single or a social welfare recipient and residence
      region (North Denmark) were especially associated with opportunistic testing
      (routine or sporadic). CONCLUSIONS: One fourth of cervical cytologies in this
      study were collected opportunistically. Compared to invited women, women
      undergoing routine opportunistic testing were more likely to be diagnosed with
      abnormal cytologies. Hence, routine opportunistic testing might serve as an
      important supplement to the systematic screening program by covering non
      participating women who may otherwise be tested with a delay or not tested at
      all. Among women tested more often than recommended (sporadic testing), no
      benefits in terms of detecting more cytological abnormalities were identified.

PMID- 26194008
TI  - Populational landscape of INDELs affecting transcription factor-binding sites in
      humans.
AB  - BACKGROUND: Differences in gene expression have a significant role in the
      diversity of phenotypes in humans. Here we integrated human public data from
      ENCODE, 1000 Genomes and Geuvadis to explore the populational landscape of INDELs
      affecting transcription factor-binding sites (TFBS). A significant fraction of
      TFBS close to the transcription start site of known genes is affected by INDELs
      with a consequent effect at the expression of the associated gene. RESULTS:
      Hundreds of TFBS-affecting INDELs (TFBS-ID) show a differential frequency between
      human populations, suggesting a role of natural selection in the spread of such
      variant INDELs. A comparison with a dataset of known human genomic regions under
      natural selection allowed us to identify several cases of TFBS-ID likely involved
      in populational adaptations. Ontology analyses on the differential TFBS-ID
      further indicated several biological processes under natural selection in
      different populations. CONCLUSION: Together, our results strongly suggest that
      INDELs have an important role in modulating gene expression patterns in humans.
      The dataset we make available, together with other data reporting variability at
      both regulatory and coding regions of genes, represent a powerful tool for
      studies aiming to better understand the evolution of gene regulatory networks in
      humans.

PMID- 26194009
TI  - Transplantation of MSCs Overexpressing HGF into a Rat Model of Liver Fibrosis.
AB  - PURPOSE: The aim of this study is to evaluate the effect of overexpressing human
      hepatocyte growth factor (HGF) for mesenchymal stem cells (MSCs) in liver
      fibrosis regeneration and magnetic resonance (MR) tracking of MSCs in rat liver.
      PROCEDURES: MSCs were transfected with ad-HGF/ad-green fluorescent protein (GFP)
      and labeled with superparamagnetic iron oxide (SPIO). The characteristics of SPIO
      HGF/MSCs were investigated. Prussian blue staining for iron assessment was
      conducted in vitro and in vivo. SPIO-HGF/MSCs (group A) or SPIO-GFP/MSCs (group
      B) were transplanted into a rat model of liver fibrosis, and MR imaging of the
      rat liver was performed. The signal to noise ratio (SNR) and R2* (1/T2*) value
      were measured. Prussian blue staining was performed to detect the in vivo
      distribution of MSCs, and liver Ki67 immunohistochemistry (IHC) staining was
      studied. The serum levels of HGF, alanine aminotransferase (ALT) and hyaluronic
      acid (HA) were determined. RESULTS: The positive rate of HGF transfection was
      93.17 % and the HGF/MSCs were labeled with SPIO successfully (97.80 +/- 1.06 %).
      Labeling of MSCs with SPIO did not alter cell proliferation in vitro. The signal
      intensity of liver T2* WI images decreased on day 1 after cell transplantation
      and recovered to pre-transplantation level on day 15 (group A) and day 13 (group
      B). The SNR of group A were significantly lower than that of group B (P = 0.006),
      and the R2* values of group A were significantly higher than those of group B (P
      < 0.001). The R2* value had a significantly negative correlation with SNR. There
      were more Prussian blue-positive cells in of group A were more than in group B in
      vivo. The positive rate of Ki67 was 16.11 +/- 2.13 %, and the serum level of
      ALT/HA was decreased in group A. CONCLUSION: HGF transfection improved MSCs
      localization in the liver and aided liver repair. The R2* value might be a
      feasible index in addition to SNR to track the SPIO-MSC transplantation in the
      liver.

PMID- 26194010
TI  - Evaluation of PET Imaging Performance of the TSPO Radioligand [18F]DPA-714 in
      Mouse and Rat Models of Cancer and Inflammation.
AB  - PURPOSE: Many radioligands have been explored for imaging the 18-kDa translocator
      protein (TSPO), a diagnostic and therapeutic target for inflammation and cancer.
      Here, we investigated the TSPO radioligand [(18)F]DPA-714 for positron emission
      tomography (PET) imaging of cancer and inflammation. PROCEDURES: [(18)F]DPA-714
      PET imaging was performed in 8 mouse and rat models of breast and brain cancer
      and 4 mouse and rat models of muscular and bowel inflammation. RESULTS:
      [(18)F]DPA-714 showed different uptake levels in healthy organs and malignant
      tissues of mice and rats. Although high and displaceable [(18)F]DPA-714 binding
      is observed ex vivo, TSPO-positive PET imaging of peripheral lesions of cancer
      and inflammation in mice did not show significant lesion-to-background signal
      ratios. Slower [(18)F]DPA-714 metabolism and muscle clearance in mice compared to
      rats may explain the elevated background signal in peripheral organs in this
      species. CONCLUSION: Although TSPO is an evolutionary conserved protein, inter-
      and intra-species differences call for further exploration of the pharmacological
      parameters of TSPO radioligands.

PMID- 26194011
TI  - Preclinical Evaluation of [(18)F]THK-5105 Enantiomers: Effects of Chirality on
      Its Effectiveness as a Tau Imaging Radiotracer.
AB  - PURPOSE: Noninvasive imaging of tau and amyloid-beta pathologies would facilitate
      diagnosis of Alzheimer's disease (AD). Recently, we have developed [(18)F]THK
      5105 for selective detection of tau pathology by positron emission tomography
      (PET). The purpose of this study was to clarify biological properties of
      optically pure [(18)F]THK-5105 enantiomers. PROCEDURES: Binding for tau
      aggregates in AD brain section was evaluated by autoradiography (ARG). In vitro
      binding assays were performed to evaluate the binding properties of enantiomers
      for AD brain homogenates. The pharmacokinetics in the normal mouse brains was
      assessed by ex vivo biodistribution assay RESULTS: The ARG of enantiomers showed
      the high accumulation of radioactivity corresponding to the distribution of tau
      deposits. In vitro binding assays revealed that (S)-[(18)F]THK-5105 has slower
      dissociation from tau than (R)-[(18)F]THK-5105. Biodistribution assays indicated
      that (S)-[(18)F]THK-5105 eliminated faster from the mouse brains and blood
      compared with (R)-[(18)F]THK-5105. CONCLUSION: (S)-[(18)F]THK-5105 could be more
      suitable than (R)-enantiomer for a tau imaging agent.

PMID- 26194013
TI  - Genome-wide uniparental disomy screen in human discarded morphologically abnormal
      embryos.
AB  - Uniparental disomy (UPD) has been shown to be rare in human normal blastocysts,
      but its frequency in discarded morphologically abnormal embryos and its relevance
      to embryonic self-correction of aneuploid remains unknown. The aim of this study
      was to detect UPD in discarded morphologically abnormal embryos. Both discarded
      morphologically abnormal embryos, including zero-pronuclear zygotes (0PN), one
      pronuclear zygotes (1PN), three-pronuclear zygotes (3PN) and 2PN embryos scored
      as low development potential were cultured into blastocysts then underwent
      trophectoderm biopsy. Genome-wide UPD screening of the trophectoderm of 241
      discarded morphologically abnormal embryo sourced blastocysts showed that UPD
      occurred in nine embryos. Five embryos exhibited UPDs with euploid chromosomes,
      and four displayed UPDs with chromosomal aneuploid. The percentage of UPDs among
      the morphologically abnormal sourced blastocysts was 3.73%, which is significant
      higher than the percentage observed in normal blastocysts. The frequency of UPD
      in 3PN-sourced blastocysts was 7.69%, which is significantly higher than that in
      normal blastocysts. This study provides the first systematic genome-wide profile
      of UPD in discarded morphologically abnormal embryos. Our results indicated that
      UPD may be a common phenomenon in discarded morphologically abnormal embryos and
      may be relevant to human embryonic self-correction. 

PMID- 26194012
TI  - Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor
      Molecular Imaging.
AB  - PURPOSE: Quantitative molecular imaging of beta cell mass (BCM) would enable
      early detection and treatment monitoring of type 1 diabetes. The glucagon-like
      peptide-1 (GLP-1) receptor is an attractive target due to its beta cell
      specificity and cell surface location. We quantitatively investigated the impact
      of plasma clearance and receptor internalization on targeting efficiency in
      healthy B6 mice. PROCEDURES: Four exenatide-based probes were synthesized that
      varied in molecular weight, binding affinity, and plasma clearance. The GLP-1
      receptor internalization rate and in vivo receptor expression were quantified.
      RESULTS: Receptor internalization (54,000 receptors/cell in vivo) decreased
      significantly within minutes, reducing the benefit of a slower-clearing agent.
      The multimers and albumin binding probes had higher kidney and liver uptake,
      respectively. CONCLUSIONS: Slow plasma clearance is beneficial for GLP-1 receptor
      peptide therapeutics. However, for exendin-based imaging of islets, down
      regulation of the GLP-1 receptor and non-specific background uptake result in a
      higher target-to-background ratio for fast-clearing agents.

PMID- 26194014
TI  - Parents Produce Explicit Cues That Help Toddlers Distinguish Joking and
      Pretending.
AB  - While separate pieces of research found parents offer toddlers cues to express
      that they are (1) joking and (2) pretending, and that toddlers and preschoolers
      understand intentions to (1) joke and (2) pretend, it is not yet clear whether
      parents and toddlers consider joking and pretending to be distinct concepts. This
      is important as distinguishing these two forms of non-literal acts could open a
      gateway to understanding the complexities of the non-literal world, as well as
      the complexities of intentions in general. Two studies found parents offer
      explicit cues to help 16- to 24-month-olds distinguish pretending and joking.
      Across an action play study (n = 25) and a verbal play study (n = 40) parents
      showed more disbelief and less belief through their actions and language when
      joking versus pretending. Similarly, toddlers showed less belief through their
      actions, and older toddlers showed less belief through their language. Toddlers'
      disbelief could be accounted for by their response to parents' language and
      actions. Thus, these studies reveal a mechanism by which toddlers learn to
      distinguish joking and pretending. Parents offer explicit cues to distinguish
      these intentions, and toddlers use these cues to guide their own behaviors, which
      in turn allows toddlers to distinguish these intentional contexts.

PMID- 26194015
TI  - The stochastic thermodynamics of a rotating Brownian particle in a gradient flow.
AB  - We compute the entropy production engendered in the environment from a single
      Brownian particle which moves in a gradient flow, and show that it corresponds in
      expectation to classical near-equilibrium entropy production in the surrounding
      fluid with specific mesoscopic transport coefficients. With temperature gradient,
      extra terms are found which result from the nonlinear interaction between the
      particle and the non-equilibrated environment. The calculations are based on the
      fluctuation relations which relate entropy production to the probabilities of
      stochastic paths and carried out in a multi-time formalism. 

PMID- 26194016
TI  - Investigation into FlhFG reveals distinct features of FlhF in regulating
      flagellum polarity in Shewanella oneidensis.
AB  - Rod-shaped bacterial cells are polarized, with many organelles confined to a
      polar cellular site. In polar flagellates, FlhF and FlhG, a multiple-domain (B-N
      G) GTPase and a MinD-like ATPase respectively, function as a cognate pair to
      regulate flagellar localization and number as revealed in Vibrio and Pseudomonas
      species. In this study, we show that FlhFG of Shewanella oneidensis (SoFlhFG), a
      monotrichous gamma-proteobacterium renowned for respiratory diversity, also play
      an important role in the flagellar polar placement and number control. Despite
      this, SoFlhFG exhibit distinct features that are not observed in the
      characterized counterparts. Most strikingly, the G domain of SoFlhF determines
      the polar placement, contrasting the N domain of the Vibrio cholerae FlhF. The
      SoFlhF N domain in fact counteracts the function of the G domain with respect to
      the terminal targeting in the absence of the B domain. We further show that
      GTPase activity of SoFlhF is essential for motility but not positioning. Overall,
      our results suggest that mechanisms underlying the polar placement of organelles
      appear to be diverse, even for evolutionally relatively conserved flagellum. 

PMID- 26194017
TI  - Detection of Dientamoeba fragilis in Portuguese children with acute
      gastroenteritis between 2011 and 2013.
AB  - Dientamoeba fragilis is an inhabitant of human gastrointestinal tract with a
      worldwide distribution. The first description considered this protozoan a rare
      and harmless commensal, since then it has struggled to gain recognition as a
      pathogen. Commercial multiplex real-time PCR was used to detect D. fragilis in
      fecal samples from hospitalized children (?18 years) with acute gastrointestinal
      disease, admitted to two hospitals of Lisbon area, with different demographic
      characteristics. A total of 176 children were studied, 103 (58.5%) male, 144
      (81.8%) children between 0 and 5 years and 32 (18.2%) above 6 years old. The
      overall protozoa frequency considering the four tested microorganisms were 8.5%
      (15/176), and the most frequently found protozoan was D. fragilis, 6.3% (11/176).
      Dientamoeba fragilis frequency was higher among older children (21.9%), than
      younger children (2.8%), and greater in boys (6.8%) than in girls (5.5%). All
      positive children presented with diarrhoea associated with vomiting, fever and
      abdominal pain. Infection was associated with the age of children (P < 0.001),
      school attendance (P = 0.002) and consumption of certain foods (P = 0.014), e.g.
      cakes with creme and ham. The frequency of diantamoebiasis found in a cohort of
      hospitalized Portuguese children, with acute gastrointestinal disease, could be
      considered a very high value when compared with the protozoan frequency normally
      associated with this pathology. 

PMID- 26194019
TI  - Highly Sensitive Mechanochromic Photonic Hydrogels with Fast Reversibility and
      Mechanical Stability.
AB  - We present a fast and efficient strategy for the preparation of photonic
      hydrogels for compression and organic solvent sensing by the self-assembly of
      monodisperse carbon-encapsulated Fe3O4 nanoparticles (NPs). The hydrogel film was
      composed of acrylamide (AM) and cross-linker N,N'-methylenebis(acrylamide) (BIS),
      and the formed 1D NPs chain structure can be fixed within the hydrogels under a
      magnetic field by in situ photopolymerization. The resulting photonic hydrogels
      display vivid structural color which can be tuned by pressing and organic solvent
      treatment. The 0.2 kPa compression applied to the photonic hydrogels can be
      detected by the 37 nm blue shift of a reflection peak. Importantly, the photonic
      hydrogels can recover to their original state (<1 s) after being compressed on a
      pattern. Moreover, the sensitivity of mechanochromic photonic hydrogels can be
      adjusted by manipulating the concentration of monomers, and a large reflection
      peak shift (4.3 kPa, 200 nm) was observed. The detection range of the compression
      sensor can thus increase from 0-4.3 to 0-130.6 kPa. The photonic hydrogels are
      nearly monochromatic, with high sensitivity and stability and fast reversibility,
      and are potentially useful in displays, diagnostics, compression and solvent
      sensing. 

PMID- 26194018
TI  - Cinnoline derivatives as human neutrophil elastase inhibitors.
AB  - Compounds that can effectively inhibit the proteolytic activity of human
      neutrophil elastase (HNE) represent promising therapeutics for treatment of
      inflammatory diseases. We present here the synthesis, structure-activity
      relationship analysis, and biological evaluation of a new series of HNE
      inhibitors with a cinnoline scaffold. These compounds exhibited HNE inhibitory
      activity but had lower potency compared to N-benzoylindazoles previously reported
      by us. On the other hand, they exhibited increased stability in aqueous solution.
      The most potent compound, 18a, had a good balance between HNE inhibitory activity
      (IC50 value = 56 nM) and chemical stability (t1/2 = 114 min). Analysis of
      reaction kinetics revealed that these cinnoline derivatives were reversible
      competitive inhibitors of HNE. Furthermore, molecular docking studies of the
      active products into the HNE binding site revealed two types of HNE inhibitors:
      molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195
      hydroxyl group at the amido moiety, and cinnoline derivatives containing an ester
      function at C-4, which is the point of attack of Ser195. 

PMID- 26194020
TI  - Imidazolium Catalysts Formed by an Iterative Synthetic Process as a Model System
      for Chemical Evolution.
AB  - Processes exhibiting diversity and selection would have been necessary to promote
      chemical evolution on early Earth. In this work, a model process was developed
      using non-kinetic selection to synthesize and isolate small molecule imidazolium
      catalysts. These catalysts were purified by affinity chromatography and recycled
      back into the process, forming a product feedback loop. In dimethylformamide, the
      catalysts activated the coupling of formaldehyde to short chain sugars. This
      sugar mixture was reacted with aniline, acetic acid, and paraformaldehyde to
      generate new catalysts. Thus chemical diversity was produced through non
      selective, multi-component synthesis. Applying sequential dilution-reaction
      purification cycles it was demonstrated that this process can function
      independently of starting catalyst. Over three process cycles, the initiator
      catalyst is effectively diluted out as a new catalyst population emerges to take
      its place. This system offers an alternative viewpoint for chemical evolution via
      the generation of small molecule organocatalysts.

PMID- 26194021
TI  - Neoplastic and non-neoplastic complications of solid organ transplantation in
      patients with preexisting monoclonal gammopathy of undetermined significance.
AB  - Monoclonal gammopathy of undetermined significance (MGUS) occurs in 3-7% of the
      elderly population, with higher prevalence in renal failure patients, and is
      associated with a 25-fold increased lifetime risk for plasma cell myeloma (PCM),
      also known as multiple myeloma. Using the California State Inpatient, Emergency
      Department, and Ambulatory Surgery Databases components of the Healthcare Cost
      and Utilization Project (HCUP), we sought to determine whether patients with MGUS
      who undergo solid organ allograft (n = 22,062) are at increased adjusted relative
      risk (aRR) for hematologic malignancy and other complications. Among solid organ
      transplant patients, patients with preexisting MGUS had higher aRR of PCM (aRR
      19.46; 95% CI 7.05, 53.73; p < 0.001), venous thromboembolic events (aRR 1.66;
      95% CI 1.15, 2.41; p = 0.007), and infection (aRR 1.24; 95% CI 1.06, 1.45; p =
      0.007). However, when comparing MGUS patients with and without solid organ
      transplant, there was decreased aRR for PCM with transplant (aRR 0.34; 95% CI
      0.13, 0.88; p = 0.027), and increased venous thromboembolic events (aRR 2.33; 95%
      CI 1.58, 3.44; p < 0.001) and infectious risks (aRR 1.44; 95% CI 1.23, 1.70; p <
      0.001). While MGUS increased the risk of PCM overall following solid organ
      transplantation, there was lower risk of PCM development compared to MGUS
      patients who did not receive a transplant. MGUS should not preclude solid organ
      transplant.

PMID- 26194022
TI  - Theoretical studies of the structure, stability, and detonation properties of
      vicinal-tetrazine 1,3-dioxide annulated with a five-membered heterocycle. 1.
      Annulation with a triazole ring.
AB  - 1,2,3,4-Tetrazine (vicinal-tetrazine) high-energy-density compounds (HEDCs) are
      receiving increasing attention due to their promise as explosives. We have
      performed a series of studies of vicinal-tetrazine 1,3-dioxides annulated with a
      range of five-membered heterocycles, considering their potential as high-energy,
      low-sensitivity explosives. In the present work, twelve 1,2,3-triazol-1,2,3,4
      tetrazine 1,3-dioxides (TTDOs; T1-T12) were studied theoretically. Their
      geometric structures in the gas phase were studied at the B3LYP/6-311++G(d,p)
      level of density functional theory (DFT). Their gas-phase enthalpies of formation
      were calculated by the homodesmotic reaction method. Their enthalpies of
      sublimation and solid-phase enthalpies of formation were also predicted. Their
      detonation properties were estimated with the Kamlet-Jacobs equations, based on
      their predicted densities and enthalpies of formation in the solid state. Their
      bond dissociation activation energies (BDAEs) and the available free space in the
      lattice of each compound were calculated to evaluate their stabilities. T2, T5,
      and T11 were found to have higher energies than RDX and acceptable stabilities,
      and are therefore considered to be the three most promising TTDOs for use as high
      energy, low-sensitivity explosives. We believe that further studies, both
      experimental and theoretical, of these three targets would be worthwhile. 

PMID- 26194023
TI  - A new exploration of the addition reaction of the silylenoid H2SiLiF with
      ethylene.
AB  - The addition reactions of the simplest silylenoid H2SiLiF with ethylene were
      studied theoretically. The geometries of the stationary points along the
      potential energy surfaces were optimized using DFT B3LYP method with the 6
      311+G(d,p) basis set, and the single point energies were calculated at QCISD/6
      311++G(d,p) level of theory. The theoretical calculations demonstrated that the
      addition reaction of H2SiLiF and C2H4 can occur through two different pathways.
      One is path A via a three-membered ring transition state, the other is path B,
      while through a four-membered ring transition state. The calculated energy
      barriers of path A and path B are 58.90 and 248.08 kJ?mol(-1), respectively.
      Therefore, pathway A is more favorable than pathway B. The solvent effect on the
      addition reactions were investigated using the PCM model, and the calculated
      results indicated that in the THF solvent, the addition reaction is much easier
      than that in vacuum. The present work provided a new pathway to synthesize
      silicon heterocyclic compounds.

PMID- 26194025
TI  - Intensive Suffering.

PMID- 26194024
TI  - Consensus statement from the 2014 International Microdialysis Forum.
AB  - Microdialysis enables the chemistry of the extracellular interstitial space to be
      monitored. Use of this technique in patients with acute brain injury has
      increased our understanding of the pathophysiology of several acute neurological
      disorders. In 2004, a consensus document on the clinical application of cerebral
      microdialysis was published. Since then, there have been significant advances in
      the clinical use of microdialysis in neurocritical care. The objective of this
      review is to report on the International Microdialysis Forum held in Cambridge,
      UK, in April 2014 and to produce a revised and updated consensus statement about
      its clinical use including technique, data interpretation, relationship with
      outcome, role in guiding therapy in neurocritical care and research applications.

PMID- 26194027
TI  - Comparison of the Prevalence and Predictors of Depression in Taiwanese and
      American Older Patients With Arthritis.
AB  - PURPOSE: To compare the prevalence and predictors of depression in Taiwanese and
      American older patients with arthritis. DESIGN AND METHODS: A secondary analysis
      was conducted to assess 151 Taiwanese and 70 American arthritic patients in
      Taipei, Taiwan and Chicago, USA. FINDINGS: The prevalence of depression of
      Taiwanese and American older arthritic patients was 34% and 40%, respectively.
      Depression was explained by life satisfaction and functional ability in Taiwanese
      patients, and by life satisfaction and level of pain in American patients.
      PRACTICE IMPLICATIONS: Nurses should assess patients' level of pain and
      functional ability, as well as their life satisfaction and depression.

PMID- 26194026
TI  - Pros and cons of using biomarkers versus clinical decisions in start and stop
      decisions for antibiotics in the critical care setting.
AB  - INTRODUCTION: Patients in the intensive care unit (ICU) frequently receive
      prolonged or even unnecessary antibiotic therapy, which selects for antibiotic
      resistant bacteria. Over the last decade there has been great interest in
      biomarkers, particularly procalcitonin, to reduce antibiotic exposure. METHODS:
      In this narrative review, we discuss the value of biomarkers and provide
      additional information beyond clinical evaluation in order to be clinically
      useful and review the literature on sepsis biomarkers outside the neonatal
      period. Both benefits and limitations of biomarkers for clinical decision-making
      are reviewed. RESULTS: Several randomized controlled trials (RCTs) have shown the
      safety and efficacy of procalcitonin to discontinue antibiotic therapy in
      patients with severe sepsis or septic shock. In contrast, there is limited
      utility of procalcitonin for treatment initiation or withholding therapy
      initially. In addition, an algorithm using procalcitonin for treatment escalation
      has been ineffective and is probably associated with poorer outcomes. Little data
      from interventional studies are available for other biomarkers for antibiotic
      stewardship, except for C-reactive protein (CRP), which was recently found to be
      similarly effective and safe as procalcitonin in a randomized controlled trial.
      We finally briefly discuss biomarker-unrelated approaches to reduce antibiotic
      duration in the ICU, which have shown that even without biomarker guidance, most
      patients with sepsis can be treated with relatively short antibiotic courses of
      approximately 7 days. CONCLUSIONS: In summary, there is an ongoing unmet need for
      biomarkers which can reliably and early on identify patients who require
      antibiotic therapy, distinguish between responders and non-responders and help to
      optimize antibiotic treatment decisions among critically ill patients. Available
      evidence needs to be better incorporated in clinical decision-making.

PMID- 26194028
TI  - Quantum mechanics of excitation transport in photosynthetic complexes: a key
      issues review.
AB  - For a long time microscopic physical descriptions of biological processes have
      been based on quantum mechanical concepts and tools, and routinely employed by
      chemical physicists and quantum chemists. However, the last ten years have
      witnessed new developments on these studies from a different perspective, rooted
      in the framework of quantum information theory. The process that more, than
      others, has been subject of intense research is the transfer of excitation energy
      in photosynthetic light-harvesting complexes, a consequence of the unexpected
      experimental discovery of oscillating signals in such highly noisy systems. The
      fundamental interdisciplinary nature of this research makes it extremely
      fascinating, but can also constitute an obstacle to its advance. Here in this
      review our objective is to provide an essential summary of the progress made in
      the theoretical description of excitation energy dynamics in photosynthetic
      systems from a quantum mechanical perspective, with the goal of unifying the
      language employed by the different communities. This is initially realized
      through a stepwise presentation of the fundamental building blocks used to model
      excitation transfer, including protein dynamics and the theory of open quantum
      system. Afterwards, we shall review how these models have evolved as a
      consequence of experimental discoveries; this will lead us to present the
      numerical techniques that have been introduced to quantitatively describe photo
      absorbed energy dynamics. Finally, we shall discuss which mechanisms have been
      proposed to explain the unusual coherent nature of excitation transport and what
      insights have been gathered so far on the potential functional role of such
      quantum features. 

PMID- 26194029
TI  - MR imaging features for improved diagnosis of hepatocellular carcinoma in the non
      cirrhotic liver: Multi-center evaluation.
AB  - PURPOSE: To determine MR-imaging features for the differentiation between
      hepatocellular carcinoma (HCC) and benign hepatocellular tumors in the non
      cirrhotic liver. MATERIAL AND METHODS: 107 consecutive patients without liver
      cirrhosis (46 male; 45 +/- 14 years) who underwent liver resection due to
      suspicion of HCC were included in this multi-center study. The following imaging
      features were assessed: lesion diameter and demarcation, satellite-lesions,
      central-scar, capsule, fat-content, hemorrhage, vein-infiltration and signal
      intensity (SI) on native T1-, T2- and dynamic-enhanced T1-weighted images (center
      versus periphery). In addition, contrast-media (CM) uptake in the liver specific
      phase was analyzed in a sub-group of 42 patients. RESULTS: Significant
      differences between HCC (n=55) and benign lesions (n=52) were shown for native T1
      , T2- and dynamic-enhanced T1-SI, fat-content, and satellite-lesions (all,
      P<.05). Independent predictors for HCC were T1-hypointensity (odds-ratio, 4.81),
      T2-hypo-/hyperintensity (5.07), lack of central tumor-enhancement (3.36), and
      satellite-lesions (5.78; all P<0.05). Sensitivity and specificity of HCC was 91%
      and 75% respectively for two out-of four independent predictors, whereas
      specificity reached 98% for all four predictors. Sub-analysis, showed significant
      differences in liver specific CM uptake between HCC (n=18) and benign lesions
      (n=24; P<0.001) and revealed lack of liver specific CM uptake (odds-ratio, 2.7)
      as additional independent feature for diagnosis of HCC. CONCLUSION: Independent
      MRI features indicating HCC are T1-hypointensity, T2-hypo- or hyperintensity,
      lack of central tumor-enhancement, presence of satellite-lesions and lack of
      liver specific CM-uptake. These features may have the potential to improve the
      diagnosis of HCC in the non-cirrhotic liver.

PMID- 26194030
TI  - Detecting epistasis from an ensemble of adapting populations.
AB  - The role that epistasis plays during adaptation remains an outstanding problem,
      which has received considerable attention in recent years. Most of the recent
      empirical studies are based on ensembles of replicate populations that adapt in a
      fixed, laboratory controlled condition. Researchers often seek to infer the
      presence and form of epistasis in the fitness landscape from the time evolution
      of various statistics averaged across the ensemble of populations. Here, we
      provide a rigorous analysis of what quantities, drawn from time series of such
      ensembles, can be used to infer epistasis for populations evolving under weak
      mutation on finite-site fitness landscapes. First, we analyze the mean fitness
      trajectory-that is, the time course of the ensemble average fitness. We show that
      for any epistatic fitness landscape and starting genotype, there always exists a
      non-epistatic fitness landscape that produces the exact same mean fitness
      trajectory. Thus, the presence of epistasis is not identifiable from the mean
      fitness trajectory. By contrast, we show that two other ensemble statistics-the
      time evolution of the fitness variance across populations, and the time evolution
      of the mean number of substitutions-can detect certain forms of epistasis in the
      underlying fitness landscape. 

PMID- 26194031
TI  - Three-dimensional kinematics of the pelvis and hind limbs in chimpanzee (Pan
      troglodytes) and human bipedal walking.
AB  - The common chimpanzee (Pan troglodytes) is a facultative biped and our closest
      living relative. As such, the musculoskeletal anatomies of their pelvis and hind
      limbs have long provided a comparative context for studies of human and fossil
      hominin locomotion. Yet, how the chimpanzee pelvis and hind limb actually move
      during bipedal walking is still not well defined. Here, we describe the three
      dimensional (3-D) kinematics of the pelvis, hip, knee and ankle during bipedal
      walking and compare those values to humans walking at the same dimensionless and
      dimensional velocities. The stride-to-stride and intraspecific variations in 3-D
      kinematics were calculated using the adjusted coefficient of multiple
      correlation. Our results indicate that humans walk with a more stable pelvis than
      chimpanzees, especially in tilt and rotation. Both species exhibit similar
      magnitudes of pelvis list, but with segment motion that is opposite in phasing.
      In the hind limb, chimpanzees walk with a more flexed and abducted limb posture,
      and substantially exceed humans in the magnitude of hip rotation during a stride.
      The average stride-to-stride variation in joint and segment motion was greater in
      chimpanzees than humans, while the intraspecific variation was similar on
      average. These results demonstrate substantial differences between human and
      chimpanzee bipedal walking, in both the sagittal and non-sagittal planes. These
      new 3-D kinematic data are fundamental to a comprehensive understanding of the
      mechanics, energetics and control of chimpanzee bipedalism. 

PMID- 26194032
TI  - Distal phalanges of Eosimias and Hoanghonius.
AB  - Seven primate distal phalanges have been identified from two middle Eocene fossil
      localities (Locality 1 and Nanbaotou) in the Yuanqu Basin, China, providing the
      first evidence of distal phalangeal morphology in Asian Eocene adapiform and
      eosimiid primates. The bones are best allocated to the basal anthropoid Eosimias
      centennicus and to hoanghoniine adapiforms. All distal phalangeal specimens
      display a morphology consistent with nail-bearing fingers and toes. The hallucal
      distal phalanx of the basal anthropoid Eosimias is more similar to that of
      primitive tarsiiforms than to crown group anthropoids. The adapiform distal
      phalanges from Locality 1 are allocated to Hoanghonius stehlini while those from
      Nanbaotou are tentatively assigned to an indeterminate hoanghoniine because
      dental remains of adapiforms have yet to be identified from this site. The distal
      phalangeal anatomy of hoanghoniines differs slightly from that documented for
      adapines and notharctines. One distal phalanx from Locality 1 shows a second
      pedal digit "grooming claw" morphology as noted for notharctines by Maiolino et
      al. (2012) and cercamoniines by Von Koenigswald et al. (2012).

PMID- 26194033
TI  - Clinical Use of CSF Neurotransmitters.
AB  - BACKGROUND: Cerebrospinal fluid neurotransmitter collection, analysis, and follow
      up are integral to the diagnosis and management of multiple inborn metabolic
      errors, some of which require prompt identification and intervention to improve
      outcome. Cerebrospinal fluid pterins and monoamine metabolites are diagnostic in
      a range of primary neurotransmitter disorders, including disorders of biogenic
      amine synthesis, metabolism, and transport. RELEVANT DISORDERS: Recently
      described mutations of the human dopamine transporter are associated with an
      elevated cerebrospinal fluid homovanillic acid:hydroxyindoleacetic acid ratio.
      Disorders of pyridoxine metabolism are also detectable via cerebrospinal fluid
      quantification of bioamines, amino acids, and pyridoxal-5-phosphate levels.
      Cerebrospinal fluid amino acids are diagnostic in disorders of gamma aminobutyric
      acid, glycine, and serine metabolism. A wide range of acquired and genetic
      disorders has also been associated with secondary alterations in cerebrospinal
      fluid levels of monoamine metabolites, glycine, and neopterin. CONCLUSIONS:
      Lumbar puncture is required to detect abnormal cerebrospinal fluid metabolites in
      a significant proportion of these disorders, including treatable entities such as
      dopa-responsive deficiencies of guanosine-5'-triphosphate cyclohydrolase I
      (Segawa disease), sepiapterin reductase, and tyrosine hydroxylase.

PMID- 26194034
TI  - Impact of acute exposure to WTC dust on ciliated and goblet cells in lungs of
      rats.
AB  - Clinical studies and the World Trade Center (WTC) Health Registry have revealed
      increases in the incidence of chronic (non-cancer) lung disorders among first
      responders (FR) who were at Ground Zero during the initial 72 h after the
      collapse. Our previous analyses of rats exposed to building-derived WTC dusts
      using exposure scenarios/levels that mimicked FR mouth-breathing showed that a
      single WTC dust exposure led to changes in expression of genes whose products
      could be involved in the lung ailments, but few other significant pathologies. We
      concluded that rather than acting as direct inducers of many of the FR health
      effects, it was more likely inhaled WTC dusts instead may have impacted on
      toxicities induced by other rescue-related co-pollutants present in Ground Zero
      air. To allow for such effects to occur, we hypothesized that the alkaline WTC
      dusts induced damage to the normal ability of the lungs to clear inhaled
      particles. To validate this, rats were exposed on two consecutive days (2 h/d, by
      intratracheal inhalation) to WTC dust (collected 12-13 September 2001) and
      examined over a 1-yr period thereafter for changes in the presence of ciliated
      cells in the airways and hyperplastic goblet cells in the lungs. WTC dust levels
      in the lungs were assessed in parallel to verify that any changes in levels of
      these cells corresponded with decreases in host ability to clear the particles
      themselves. Image analyses of the rat lungs revealed a significant decrease in
      ciliated cells and increase in hyperplastic goblet cells due to the single series
      of WTC dust exposures. The study also showed there was only a nominal non
      significant decrease (6-11%) in WTC dust burden over a 1-yr period after the
      final exposure. These results provide support for our current hypothesis that
      exposure to WTC dusts caused changes in airway morphology/cell composition; such
      changes could, in turn, have led to potential alterations in the
      clearance/toxicities of other pollutants inhaled at Ground Zero in the critical
      initial 72-h period. 

PMID- 26194035
TI  - A mechanistic review of silica-induced inhalation toxicity.
AB  - Crystalline forms of silica have been proposed as positive control material for
      the toxicity test of inhaled particulate/fibrous matter, although mechanism of
      silica-induced inhalation toxicity has not yet been established. Inhalation
      exposure of alpha-quartz to rodents induces severe lung inflammation and fibrosis
      only after a certain period of latency, despite strong surface reactivity. The
      delayed occurrence of inhalation toxicity by alpha-quartz may be largely
      attributed to the sequestration of alpha-quartz particles by alternatively
      activated (M2) macrophages that express abundant levels of scavenger receptors
      but are relatively insensitive to inflammatory stimuli. When exposure to alpha
      quartz continues, lung dust burden reaches a particle overload level, at which M2
      macrophages cannot accommodate further quartz particles. Free quartz particles
      distributed in the interstitium interact with another subtype of macrophages,
      classically activated/inflammatory (M1) macrophages, which secrete various
      inflammatory cytokines, but silica-laden M1 macrophages initiate granuloma
      formation, which sequesters silica particles, too. Furthermore, the ability of M2
      macrophages to clear foreign matter, particularly bacterial endotoxins
      [lipopolysaccharides (LPS)], may decrease due to alpha-quartz cytotoxicity. When
      LPS concentration in the lung reaches a certain level, LPS primes M1 macrophages
      to prepare for interleukin-1beta production in response to alpha-quartz and also
      stimulates M1 macrophages and plasmacytoid dendritic cells (pDCs) to produce
      tumor necrosis factor (TNF)-alpha and interferon (IFN)-beta, respectively.
      Besides, IFN-beta may enhance TNF-alpha production in LPS-stimulated M1
      macrophages. The elevated levels of inflammatory cytokines produce progressive
      lung inflammation and fibrosis. 

PMID- 26194037
TI  - Syringomyelia in VACTERL-H association: a new neurological feature in an adult
      patient.

PMID- 26194036
TI  - Olfactory deposition of inhaled nanoparticles in humans.
AB  - CONTEXT: Inhaled nanoparticles can migrate to the brain via the olfactory bulb,
      as demonstrated in experiments in several animal species. This route of exposure
      may be the mechanism behind the correlation between air pollution and human
      neurodegenerative diseases, including Alzheimer's disease and Parkinson's
      disease. OBJECTIVES: This article aims to (i) estimate the dose of inhaled
      nanoparticles that deposit in the human olfactory epithelium during nasal
      breathing at rest and (ii) compare the olfactory dose in humans with our earlier
      dose estimates for rats. MATERIALS AND METHODS: An anatomically-accurate model of
      the human nasal cavity was developed based on computed tomography scans. The
      deposition of 1-100 nm particles in the whole nasal cavity and its olfactory
      region were estimated via computational fluid dynamics (CFD) simulations. Our CFD
      methods were validated by comparing our numerical predictions for whole-nose
      deposition with experimental data and previous CFD studies in the literature.
      RESULTS: In humans, olfactory dose of inhaled nanoparticles is highest for 1-2 nm
      particles with ~1% of inhaled particles depositing in the olfactory region. As
      particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled
      particles. DISCUSSION AND CONCLUSION: Our results suggest that the percentage of
      inhaled particles that deposit in the olfactory region is lower in humans than in
      rats. However, olfactory dose per unit surface area is estimated to be higher in
      humans in the 1--7 nm size range due to the larger inhalation rate in humans.
      These dose estimates are important for risk assessment and dose-response studies
      investigating the neurotoxicity of inhaled nanoparticles.

PMID- 26194038
TI  - Eliminating mother-to-child transmission of the human immunodeficiency virus in
      sub-Saharan Africa: The journey so far and what remains to be done.
AB  - This review was carried out to provide a comprehensive overview of efforts toward
      elimination of mother-to-child transmission (MTCT) of human immunodeficiency
      virus (HIV) with respect to progress, challenges, and recommendations in 21 sub
      Saharan African priority countries. We reviewed literature published from 2011 to
      April 2015 using 3 databases; PubMed, Scopus, and Web of Science, as well as the
      2014 Global Plan Progress Report. A total of 39 studies were included. Between
      2009 and 2013, there was a 43% reduction in new HIV infections, the final MTCT
      rate was reduced from 28% to 18%, and antiretroviral therapy (ART) coverage
      increased from 11% to 24%. Challenges included poor adherence to antiretroviral
      therapy, poor linkage between mother-child pairs and post-natal healthcare
      services low early infant diagnosis coverage, low pediatric ART coverage, and
      high unmet needs for contraceptive services. Future recommendations include
      identification of key barriers, health system strengthening, strengthening
      community involvement, and international collaboration. There has been
      significant progress toward eliminating MTCT of HIV, but more effort is still
      needed. 

PMID- 26194039
TI  - Bone Pose Estimation in the Presence of Soft Tissue Artifact Using Triangular
      Cosserat Point Elements.
AB  - Accurate estimation of the position and orientation (pose) of a bone from a
      cluster of skin markers is limited mostly by the relative motion between the bone
      and the markers, which is known as the soft tissue artifact (STA). This work
      presents a method, based on continuum mechanics, to describe the kinematics of a
      cluster affected by STA. The cluster is characterized by triangular cosserat
      point elements (TCPEs) defined by all combinations of three markers. The effects
      of the STA on the TCPEs are quantified using three parameters describing the
      strain in each TCPE and the relative rotation and translation between TCPEs. The
      method was evaluated using previously collected ex vivo kinematic data. Femur
      pose was estimated from 12 skin markers on the thigh, while its reference pose
      was measured using bone pins. Analysis revealed that instantaneous subsets of
      TCPEs exist which estimate bone position and orientation more accurately than the
      Procrustes Superimposition applied to the cluster of all markers. It has been
      shown that some of these parameters correlate well with femur pose errors, which
      suggests that they can be used to select, at each instant, subsets of TCPEs
      leading an improved estimation of the underlying bone pose. 

PMID- 26194040
TI  - Full-Length Recombinant Human Proteoglycan 4 Interacts with Hyaluronan to Provide
      Cartilage Boundary Lubrication.
AB  - Proteoglycan 4 (PRG4) is a mucin-like glycoprotein present in synovial fluid and
      at the surface of articular cartilage. The objectives of this study were to (1)
      assess the articular cartilage surface adsorption and in vitro cartilage boundary
      lubricating ability of full-length recombinant human PRG4 (rhPRG4), and (2)
      cartilage boundary lubricating ability of purified rhPRG4, both alone and in
      combination with hyaluronan (HA). rhPRG4 adsorption onto articular cartilage
      explants was assessed by immunohistochemistry and dot blot. An in vitro cartilage
      cartilage friction test was used to assess rhPRG4's cartilage boundary
      lubricating ability compared to bovine PRG4, and that of purified rhPRG4 both
      alone and in combination with HA. rhPRG4 was able to adsorb to the articular
      surface, as well as the cut surface, of cartilage explants. The kinetic
      coefficient of friction of rhPRG4 was similar to that of PRG4 (p = 0.16) and
      lower than phosphate-buffered saline (p < 0.05), while that of purified rhPRG4 +
      HA was significantly lower than rhPRG4 alone (p < 0.05). This study demonstrates
      that rhPRG4 can adsorb to an intact articular cartilage surface and functions as
      an effective boundary lubricant, both alone and with HA, and provides the
      foundation for in vivo evaluation of this clinically relevant full-length rhPRG4
      for treatment of osteoarthritis.

PMID- 26194041
TI  - Ocular Manifestation of Diphtheria in a Fully Immunised Infant.

PMID- 26194042
TI  - Decreased Overall and Bladder Cancer-Specific Mortality with Adjuvant
      Chemotherapy After Radical Cystectomy: Multivariable Competing Risk Analysis.
AB  - Adding chemotherapy to radical cystectomy (RC) may improve outcome. Neoadjuvant
      treatment is advocated by guidelines based on meta-analysis data but is severely
      underused in clinical practice. Adjuvant treatment of patients at risk could be
      an alternative. We analyzed a sample of 798 patients who underwent RC between
      1993 and 2011 for high-risk superficial or muscle-invasive urothelial or
      undifferentiated bladder cancer, of which 23% received adjuvant cisplatin-based
      chemotherapy and %5 received neoadjuvant chemotherapy. The use of adjuvant
      chemotherapy was an independent predictor of decreased overall mortality (hazard
      ratio [HR]: 0.50; 95% confidence interval [CI], 0.38-0.66; p<0.0001) and bladder
      cancer-specific mortality (HR: 0.71; 95% CI, 0.52-0.97; p=0.0321), but it was not
      associated with competing mortality. Similar figures were obtained when analyzing
      the number of cisplatin-containing cycles administered or when restricting the
      analysis to patients with lymph node-positive or extravesical but lymph node
      negative disease, suggesting a mortality-reducing treatment effect after
      adjusting for several patient- and tumor-related confounders. Future trials
      should directly compare the concepts of neoadjuvant and adjuvant application of
      chemotherapy in candidates for RC. PATIENT SUMMARY: Adjuvant chemotherapy may
      decrease overall and bladder cancer-specific mortality after radical cystectomy
      (RC). Future trials should directly compare the concepts of neoadjuvant and
      adjuvant application of chemotherapy in candidates for RC.

PMID- 26194043
TI  - Tibial Nerve Stimulation for Treating Neurogenic Lower Urinary Tract Dysfunction:
      A Systematic Review.
AB  - CONTEXT: Tibial nerve stimulation (TNS) is a promising therapy for non-neurogenic
      lower urinary tract dysfunction and might also be a valuable option for patients
      with an underlying neurological disorder. OBJECTIVE: We systematically reviewed
      all available evidence on the efficacy and safety of TNS for treating neurogenic
      lower urinary tract dysfunction (NLUTD). EVIDENCE ACQUISITION: The review was
      performed according to the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses Statement. EVIDENCE SYNTHESIS: After screening 1943 articles, 16
      studies (4 randomized controlled trials [RCTs], 9 prospective cohort studies, 2
      retrospective case series, and 1 case report) enrolling 469 patients (283 women
      and 186 men) were included. Five studies reported on acute TNS and 11 on chronic
      TNS. In acute and chronic TNS, the mean increase of maximum cystometric capacity
      ranged from 56 to 132mL and from 49 to 150mL, and the mean increase of bladder
      volume at first detrusor overactivity ranged from 44 to 92mL and from 93 to
      121mL, respectively. In acute and chronic TNS, the mean decrease of maximum
      detrusor pressure during the storage phase ranged from 5 to 15cm H2O and from 4
      to 21cm H2O, respectively. In chronic TNS, the mean decrease in number of voids
      per 24h, in number of leakages per 24h, and in postvoid residual ranged from 3 to
      7, from 1 to 4, and from 15 to 55mL, respectively. No TNS-related adverse events
      have been reported. Risk of bias and confounding was high in most studies.
      CONCLUSIONS: Although preliminary data of RCTs and non-RCTs suggest TNS might be
      effective and safe for treating NLUTD, the evidence base is poor, derived from
      small, mostly noncomparative studies with a high risk of bias and confounding.
      More reliable data from well-designed RCTs are needed to reach definitive
      conclusions. PATIENT SUMMARY: Early data suggest tibial nerve stimulation might
      be effective and safe for treating neurogenic lower urinary tract dysfunction,
      but more reliable evidence is required.

PMID- 26194044
TI  - Anti-programmed Cell Death Protein 1 (PD-1) Antibody Nivolumab Leads to a
      Dramatic and Rapid Response in Papillary Renal Cell Carcinoma with Sarcomatoid
      and Rhabdoid Features.

PMID- 26194045
TI  - Influence of timing on electrodiagnosis of Guillain-Barre syndrome in the first
      six weeks: a retrospective study.
AB  - The effect of timing is uncertain on the electrophysiology of Guillain-Barre
      syndrome (GBS). On this may however depend the usefulness of systematic serial
      studies performed at specific time intervals. We retrospectively analyzed records
      of 118 consecutive patients with GBS from Birmingham, U.K. (2001-2012), studied
      between 0-14days, or, 15-42days post-onset using new criteria which we recently
      proposed [4]. Rates of acute inflammatory demyelinating polyneuropathy (AIDP)
      (p=0.45), axonal GBS (p=0.32) and equivocal forms (p=0.46) were similar for both
      timings. Similarly, no significant differences between timings were observed
      using Hadden et al.'s criteria. Proportions were comparable to published serial
      studies for both timings, for AIDP (p=0.25; p=0.10) and axonal GBS (p=0.73;
      p=0.56) but were higher than with serial studies for equivocal forms in patients
      studied on days 0-14 (p=0.012), although not in those studied on days 15-42
      (p=0.17). This suggests that over the initial 6weeks post-onset, timing fails to
      influence subtype proportions in a large GBS cohort, irrespective of criteria
      used. Repeat studies appear therefore unlikely to be helpful when systematically
      performed within this time frame, except in equivocal cases. The benefit of
      repeat studies remains possible at other times but may need to be individualized,
      and requires future prospective evaluation.

PMID- 26194046
TI  - More evidence of a neurocardiac prodrome in anti-LGI1 encephalitis.

PMID- 26194047
TI  - Hindi language tool for assessing pediatric cochlear implant recipients.
AB  - INTRODUCTION: Presently, in India, western material is mainly used for the
      assessment and planning of habilitation activities for paediatric cochlear
      implant (CI) recipients. There is no assessment material available in Hindi.
      Therefore, the present study aimed to develop a parental questionnaire to assess
      auditory, speech and language skills of paediatric CI recipients in Hindi
      language for the age range of 3-7 years. METHOD: Most commonly used assessment
      material/curricula used in Indian cochlear implant clinics and primary school
      Hindi language teachers were consulted during the development of the parental
      questionnaire. The developed questionnaire was then given to the parents of 50
      normal hearing, Hindi speaking children in the age range of 3-7 years, five
      experienced speech and language pathologist working in the field of paediatric CI
      and to the same primary school Hindi language teachers who were consulted in the
      beginning to validate the content of the questionnaire. Based on the feedback
      from parents, personal observations and views from other professionals, the
      questionnaire was modified to incorporate the suggestions and the questionnaire
      was finalized. The final questionnaire has three subtests (1, 2 and 3) to assess
      auditory, language and speech skills of the CI recipients respectively. The final
      questionnaire was given to the Hindi speaking parents of 50 CI recipients in the
      age range of 3-7 years who fulfilled the eligibility criteria. Both the parents
      were asked to fill the final questionnaire together in the clinic at 0 (switch
      on), 1, 6 and 12 months post switch-on of the implant. RESULT AND DISCUSSION: All
      the cochlear implant recipients could be evaluated by the questionnaire and none
      of the recipient scored zero on the questionnaire at any time interval. The
      developed questionnaire had shown high reliability and internal consistency
      producing alpha values of 0.9201, 0.7425 and 0.9311 for the subtest 1, 2 and the
      entire questionnaire respectively. The alpha value was not calculated for subtest
      3 as it was a rating scale and not much variation was noticed in this section.

PMID- 26194048
TI  - Is inpatient admission necessary following removal of airway foreign bodies?
AB  - OBJECTIVE: To determine the need for postoperative admission following airway
      foreign body retrieval by examining the preoperative presentation, operative
      details, and postoperative recovery. INTRODUCTION: Inpatient admission following
      foreign body removal is common, however little evidence supports this practice.
      In the era of cost containment and prudent utilization of hospital resources,
      careful examination of the postoperative course following airway foreign body
      removal is required. METHODS: A retrospective review of cases over a four year
      period from a pediatric tertiary care pediatric hospital was performed. All
      children presenting with concerns for airway foreign bodies were included.
      Children without identification of an airway foreign body during bronchoscopy
      were excluded. Microlaryngoscopy and bronchoscopy with airway foreign body
      extraction was performed. Details concerning demographics, operative findings,
      and pre and postoperative course including pulse oximetry were collected. All
      respiratory events, intubations, and persistent oxygen requirements were
      investigated. RESULTS: Thirty five children underwent successful airway foreign
      body removal. The mean age was 3.2+/-2.6 years with a preponderance of males
      (68.6%). The retrieved items included: nuts (31.4%), popcorn (14.3%), seeds
      (8.6%), and inorganic materials (34.3%). Mean operative time was 29.7+/-25.6min.
      The mean length of stay following surgery was 1.3+/-1.9 days. Most patients
      (31/35) (88.6%) were extubated prior to transfer to recovery. 30/35 (85.7%)
      patients required no supplemental oxygen without desaturations following post
      anesthesia care unit (PACU) recovery. One patient developed laryngospasm
      requiring reintubation within 15min of surgery. Two patients were intubated prior
      to transfer for respiratory distress and remained intubated following surgery.
      Two patients breathing spontaneously prior to surgery were left intubated
      following surgery secondary to prolonged pneumonia treatment or multifocal
      foreign bodies with airway edema. All patients subsequently extubated without
      complication. In total, 30/31 (96.7%) of patients extubated in the operating room
      returned to room air oxygenation within 2h of surgery. CONCLUSIONS: PACU
      observation and discharge is feasible in select children following airway foreign
      body extraction. Patients carefully monitored in the recovery unit without oxygen
      requirement are candidates for discharge. Inpatient monitoring is advised in
      'children with preoperative respiratory distress or a complicated operative
      course.

PMID- 26194049
TI  - Second primary malignancies after radiotherapy including HDR (252)Cf
      brachytherapy for cervical cancer.
AB  - PURPOSE: Second primary malignancies (SPMs) are among the most serious late
      adverse effects after radiotherapy experienced over time by the increasing
      population of cancer survivors worldwide. The study aim was to determine the rate
      and distribution of SPMs for neutron- and photon-emitting brachytherapy (BT)
      sources for patients treated for cervical cancer. METHODS AND MATERIALS: The
      cohort comprised 662 patients with invasive cervical cancer (Stages IIB and IIIB)
      and contributed 5,224 patient-years (PY) of observation. These patients were
      treated by radiotherapy during the 1989-1999 year period with cobalt-60 source
      ((60)Co) teletherapy. The first group of patients (N = 375; 3,154 PY) received
      high-dose-rate (HDR) californium-252 source ((252)Cf) BT, whereas the second
      group (N = 287; 2,070 PY) received HDR (60)Co BT. RESULTS: Over a 25-year period,
      35 SPMs were observed, amounting to 5.3% of all observed patients: in 16 (2.4%)
      heavily, 2 (0.3%) moderately, 14 (2.1%) lightly irradiated body sites, and 3
      (0.5%) other sites. Of these, 21 cases (5.6%) were observed in the HDR (252)Cf BT
      group, whereas 14 cases (4.9%) were observed in the HDR (60)Co BT group.
      Exposures received during (60)Co teletherapy and HDR BT with either (252)Cf or
      (60)Co had statistically equivalent (p = 0.68) effects on SPM development.
      CONCLUSIONS: Cure rates are improving, and therefore, there are more long-term
      survivors from cervical cancer. This study shows no significant difference in
      rates or distribution of SPMs in women treated with neutron BT compared with
      photon BT (p = 0.68). After reviewing related literature and our research
      results, it is evident that a detailed investigation of SPM frequency,
      localization, and dose to adjacent organs is a suitable topic for further
      research.

PMID- 26194050
TI  - Moesin regulates the motility of oral cancer cells via MT1-MMP and E
      cadherin/p120-catenin adhesion complex.
AB  - OBJECTIVE: The present study aimed to clarify the role of Moesin in oral squamous
      cell carcinoma (OSCC) progression, especially in regulation of cell motility.
      MATERIALS AND METHODS: Immunohistochemistry and western blotting were used to
      investigate the expression of Moesin, E-cadherin, p120-catenin and MT1-MMP in
      normal epithelia, dysplasia and OSCCs. Then, Moesin was knockdown by siRNA in
      OSCC cell lines, WSU-HN6 and CAL27, and the biological role of Moesin in cell
      adhesion and motility was evaluated by transwell system, cell spreading and
      aggregation assays. The interactions between Moesin, MT1-MMP and E-cadherin/p120
      catenin complex were determined by co-immunoprecipitation and immunofluorescence.
      RESULTS: Moesin expression was found decreased in the membrane and increased in
      cytoplasm during the malignant transformation of oral epithelia, and cytoplasmic
      overexpression of Moesin correlated with nodal metastasis and poor prognosis of
      OSCCs. Furthermore, Moesin-silencing induced an increased cell-cell adhesion but
      decreased invasiveness, which was subsequently demonstrated might due to Moesin
      mediated E-cadherin and p120-catenin interaction. Meantime, Moesin-silencing
      significantly down-regulated MT1-MMP expression, accompanied by reduced cell
      motility and impaired filopodia formation, which was also observed when MT1-MMP
      knockdown by RNAi or tissue inhibitor (TIMP2), indicating the involvement of MT1
      MMP in Moesin-mediated cell motility. Finally, the relationship between Moesin, E
      cadherin and MT1-MMP was confirmed in OSCC tissue samples. CONCLUSION: Taken
      together, our results indicate Moesin may regulate cell motility through its
      interactions with MT1-MMP and E-cadherin/p120-catenin adhesion complex and
      cytoplasmic expression of Moesin correlates with nodal metastasis and poor
      prognosis of OSCCs, indicating Moesin may be a potential candidate for targeted
      gene therapy for OSCCs.

PMID- 26194051
TI  - Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte
      derived macrophages.
AB  - Neutrophil apoptosis and clearance by macrophages are essential for wound
      healing. Evidence suggests that hyperbaric oxygen (HBO) exposure may enhance
      neutrophil apoptosis, but HBO effects leading to neutrophil clearance by
      macrophages are still unclear. In the current study, bovine neutrophils and
      monocyte-derived macrophages (MDMPhi) were co-cultured under HBO (97.9% O2, 2.1%
      CO2 at 2.4 atm absolute (ATA)) (1 atm = 101.325 kPa), hyperbaric normoxia (8.8%
      O2 at 2.4 ATA), normobaric hyperoxia (95% O2, 5% CO2), normoxia (air), and
      normobaric hypoxia (5% O2, 5% CO2). Phagocytosis of fresh and 22 h aged
      neutrophils by MDMPhi was increased after HBO pre-treatment, assessed using flow
      cytometry and light microscopy. Enhanced clearance of neutrophils was accompanied
      by an increase in H2O2 levels following HBO pre-treatment with upregulation of IL
      10 (anti-inflammatory cytokine) mRNA expression in LPS-stimulated MDMPhi that had
      ingested aged neutrophils. TNF-alpha (pro-inflammatory cytokine) gene expression
      did not change in LPS-stimulated MDMPhi that had ingested fresh or aged
      neutrophils after HBO, pressure, and hyperoxia. These findings suggest that HBO
      activated MDMPhi participate in the clearance of apoptotic cells. Uptake of
      neutrophils by MDMPhi exposed to HBO may contribute to resolution of
      inflammation, because HBO induced up-regulation of IL-10 mRNA expression. 

PMID- 26194052
TI  - Modified veranda-trap hut for improved evaluation of vector control
      interventions.
AB  - Experimental huts with veranda traps have been used in Tanzania since 1963 for
      the study of residual insecticides for use with insecticide-treated nets and
      indoor residual spraying. Mosquitoes are allowed unrestricted entry through the
      eaves to facilitate the collection of an estimable proportion of mosquitoes that
      attempt to exit through the eave gaps, which are left open on two sides of the
      hut. This study was designed to validate the use of eave baffles to funnel entry
      and to prevent mosquito escape, and to determine biting times of Anopheles
      arabiensis (Patton) (Diptera: Culicidae). Anopheles arabiensis and Culex
      quinquefasciatus (Say) (Diptera: Culicidae) were released into the room at 20.30
      hours and collected the following morning from veranda traps, window traps and
      the room. Centers for Disease Control light traps hung overnight next to
      volunteers were emptied every 2 h to determine peak biting times. A total of 55%
      of An. arabiensis were trapped before 22.30 hours and the highest peak in
      'biting' was recorded during 18.30-20.30 hours. Of the released An. arabiensis
      that exited into veranda traps, 7% were captured in veranda traps entered through
      baffles and 93% were captured in traps entered through unmodified eaves. When
      veranda screens were left open to allow for escape outdoors, recapture rates were
      68% for huts with eave baffles and 39% for huts with unmodified eaves. The
      comparison of open eaves with baffled eaves validated the assumption that in huts
      of the traditional non-baffled design, 50% of mosquitoes escape through open
      eaves. Eave baffles succeeded in reducing the potential for mosquito exit and
      produced more precise estimates of effect. 

PMID- 26194053
TI  - Anticoagulant effects of inhaled unfractionated heparin in the dog as determined
      by partial thromboplastin time and factor Xa activity.
AB  - OBJECTIVE: To evaluate the anticoagulant effects of inhaled heparin in dogs.
      DESIGN: This study was conducted in 3 phases. In phase 1, bronchoalveolar lavage
      fluid (BALf) was collected to generate an in vitro calibration curve to relate
      heparin concentration to the activated partial thromboplastin time (aPTT). In
      phase 2, heparin was administered via nebulization to determine the threshold
      dose needed to prolong systemic aPTT. In phase 3, the local anticoagulant
      activity of inhaled heparin was determined by measurement of BALf anti-Xa
      activity and aPTT. SETTING: University teaching hospital. ANIMALS: Six healthy
      intact female Walker Hounds were used in this study. Two dogs were used for each
      phase. INTERVENTIONS: Inhaled unfractionated sodium heparin was administered in
      doses ranging from 50,000 to 200,000 IU. RESULTS: In vitro addition of heparin to
      BALf caused a prolongation in aPTT. Inhaled heparin at doses as high as 200,000
      IU failed to prolong systemic aPTT, and a threshold dose could not be determined.
      No significant local anticoagulant effects were detected. CONCLUSIONS: Even at
      doses higher than those known to be effective in people, inhaled heparin appears
      to have no detectable local or systemic anticoagulant effects in dogs with the
      current delivery method.

PMID- 26194055
TI  - Tropical Medicine & International Health.

PMID- 26194054
TI  - Alternative splicing mechanisms orchestrating post-transcriptional gene
      expression: intron retention and the intron-rich genome of apicomplexan
      parasites.
AB  - Apicomplexan parasites including Toxoplasma gondii and Plasmodium species have
      complex life cycles that include multiple hosts and differentiation through
      several morphologically distinct stages requiring marked changes in gene
      expression. This review highlights emerging evidence implicating regulation of
      mRNA splicing as a mechanism to prime these parasites for rapid gene expression
      upon differentiation. We summarize the most important insights in alternative
      splicing including its role in regulating gene expression by decreasing mRNA
      abundance via 'Regulated Unproductive Splicing and Translation'. As a related but
      less well-understood mechanism, we discuss also our recent work suggesting a role
      for intron retention for precluding translation of stage specific isoforms of T.
      gondii glycolytic enzymes. We additionally provide new evidence that intron
      retention might be a widespread mechanism during parasite differentiation.
      Supporting this notion, recent genome-wide analysis of Toxoplasma and Plasmodium
      suggests intron retention is more pervasive than heretofore thought. These
      findings parallel recent emergence of intron retention being more prevalent in
      mammals than previously believed, thereby adding to the established roles in
      plants, fungi and unicellular eukaryotes. Deeper mechanistic studies of intron
      retention will provide important insight into its role in regulating gene
      expression in apicomplexan parasites and more general in eukaryotic organisms. 

PMID- 26194056
TI  - Downregulation of Glutamate Transporter EAAT4 by Conditional Knockout of Rheb1 in
      Cerebellar Purkinje Cells.
AB  - Excitatory amino acid transporter 4 (EAAT4) is believed to be critical to the
      synaptic activity of cerebellar Purkinje cells by limiting extracellular
      glutamate concentrations and facilitating the induction of long-term depression.
      However, the modulation of EAAT4 expression has not been elucidated. It has been
      shown that Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin
      (mTOR) signaling plays essential roles in the regulation of protein translation,
      cell size, and cell growth. In addition, we previously found that a cascade
      including mTOR suppression and Akt activation induces increased expression of
      EAAT2 in astrocytes. In the present work, we explored whether Rheb/mTOR signaling
      is involved in the regulation of EAAT4 expression using conditional Rheb1
      knockout mice. Our results demonstrated that Rheb1 deficiency resulted in the
      downregulation of EAAT4 expression, as well as decreased activity of mTOR and
      increased activity of Akt. The downregulation of EAAT4 was also confirmed by
      reduced EAAT4 currents and slowed kinetics of alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid receptor-mediated currents. On the other hand,
      conditional knockout of Rheb1 did not alter the morphology of Purkinje cell layer
      and the number of Purkinje cells. Overall, our findings suggest that small GTPase
      Rheb1 is a modulator in the expression of EAAT4 in Purkinje cells.

PMID- 26194057
TI  - Use of Heparin in Acute Ischemic Stroke: Is There Still a Role?
AB  - Heparin has long been a contested therapy in acute ischemic stroke (AIS). In
      current practice, heparin is considered on a case-by-case basis, but there is no
      consensus as to the appropriate timing of anticoagulation or for which ischemic
      stroke subtypes heparin may be beneficial. To provide better clarity on this
      issue, we review current research focusing on the use of heparin in AIS in each
      stroke subtype and subsequently make recommendations to provide readers with a
      systematic approach to managing complex stroke patients for which acute
      anticoagulation may be valuable. We conclude that there are certain
      subpopulations of ischemic stroke patients that may derive benefit from heparin
      when given acutely, including patients with symptomatic large artery stenosis >70
      %, non-occlusive intraluminal thrombus, and in patients with high-risk cardiac
      conditions including left ventricular thrombus, left ventricular assist devices,
      and mechanical heart valves.

PMID- 26194058
TI  - Sensing cisplatin-induced permeation of single live human bladder cancer cells by
      scanning electrochemical microscopy.
AB  - Cisplatin is a widely used anti-cancer agent, which was believed to trigger
      apoptosis of cancer cells by forming DNA adducts. However, recent studies
      evidenced a cisplatin-induced extrinsic apoptotic pathway through interaction
      with plasma membranes. We present quantitative time-course imaging of cisplatin
      induced permeation of ferrocenemethanol to single live human bladder cancer cells
      (T24) using scanning electrochemical microscopy (SECM). Simultaneous
      quantification of cellular topography and membrane permeability was realized by
      running SECM in the depth scan mode. It was demonstrated that the acute addition
      of cisplatin to the outer environment of T24 cells immediately induced membrane
      permeability change in 5 min, which indicated a loosened structure of the
      cellular membrane upon cisplatin dosage. The cisplatin-induced permeation of T24
      cells might be a one-step action, an extrinsic mechanism, since the cell response
      was quick, and no continuous increase in the membrane permeability was observed.
      The time-lapse SECM depth scan method provided a simple and facile way of
      monitoring cisplatin-induced membrane permeability changes. Our study is
      anticipated to lead to a methodology of screening anti-cancer drugs through their
      interactions with live cells. 

PMID- 26194059
TI  - Evidence for glycosylation as a regulator of the pigmentary system: key roles of
      sialyl(alpha2-6)gal/GalNAc-terminated glycans in melanin synthesis and transfer.
AB  - The major regulators of melanogenesis are glycoproteins, however no role for
      glycosylation in the pathway has yet been described. We stained skin biopsies and
      melanocyte-keratinocyte co-cultures with a panel of 20 lectins as oligosaccharide
      markers. Notably, the Elderberry Bark Lectin (EBL/SNA) stained melanocytes in
      both systems. EBL binds the sequence Neu5Ac(alpha(2-6)Gal/GalNAc)- at the termini
      of some oligosaccharide antennae. We used inhibitors of synthesis and/or binding
      of this sequence to assess effects on pigmentation. METHODS: Cell culture, lectin
      histochemistry, siRNA transfection, and assays for dopa oxidase and melanin were
      carried out by standard techniques. RESULTS: 6'-sialyllactose, a short homolog of
      the sequence in question, anti-sialyltransferase 6 (ST6) siRNA, and cytidine, a
      sialyltransferase (ST) inhibitor, each inhibited EBL binding, melanogenesis and
      melanosome transfer. Unexpectedly, 3'-sialyllactose and siRNA for ST3, chosen as
      a negative controls, also inhibited these processes. Though strong inhibitors of
      melanization, none of the agents affected tyrosinase/dopa oxidase activity,
      indicating previously unrecognized post-tyrosinase regulation of melanization.
      CONCLUSIONS: We report for the first time that Neu5Ac (alpha(2-6)Gal/GalNAc)- and
      possibly Neu5Ac(alpha(2-3)Gal/GalNAc)-terminated oligosaccharides play multiple
      roles in melanin synthesis and transfer.

PMID- 26194060
TI  - Hypoxia remodels the composition of the constituent ceramide species of HexCer
      and Hex2Cer with phytosphingosine and hydroxy fatty acids in human colon cancer
      LS174T cells.
AB  - Oxygen-requiring enzymes, such as Delta4-desaturase (dihydroceramide desaturase),
      sphingolipid Delta4-desaturase/C-4-hydroxylase, and fatty acid 2-hydroxylase are
      involved in ceramide synthesis. We prepared free ceramides, sphingomyelins and
      glycosphingolipids (GSLs) from cancer cells cultivated under conditions of
      normoxia and hypoxia, and analyzed these compounds using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. Human colon cancer LS174T
      cells were employed because these cells highly express hydroxyl fatty acids and
      phytosphingosine (t18:0) which are expected to be greatly influenced by changes
      in oxygen levels. As expected, the populations of dihydro-species of free
      ceramide and sphingomyelin with C16:0 non-hydroxy fatty acid were elevated, and
      the populations of HexCers and Hex2Cers, composed of C16:0 or C16:0 hydroxy fatty
      acid (C16:0h), and sphingosine (d18:1) or t18:0, were decreased under hypoxia.
      However, appreciable populations of HexCer and Hex2Cer species of C24:0 or C24:0h
      and t18:0 remained. These results suggest that the individual species of GSLs
      with fatty acids possessing different alkyl chain lengths, either non-hydroxy
      fatty acids or hydroxyl fatty acids, may be metabolized individually. 

PMID- 26194061
TI  - The influence of ovariectomy on anti-convulsant effect of pioglitazone in mice.
AB  - The anti-convulsant effects of pioglitazone in male animals have been reported in
      previous studies. Both clinical and animal studies demonstrated that ovarian
      hormones can influence seizure activity. Pioglitazone has direct effects on
      ovaries and changes the level of gonadal hormones. In the current study, we
      examined the influence of ovariectomy on seizure threshold in pioglitazone
      treated female mice. Two models of intravenous and intraperitoneal
      pentylenetetrazole-induced clonic seizures were used to analyze the effect of
      pioglitazone in sham and ovariectomized female mice. Different doses of
      pioglitazone were administered orally for 10 days in different groups. We
      demonstrated that chronic administration of pioglitazone (10 and 20mg/kg)
      increased clonic seizure threshold in intravenous pentylenetetrazole seizure
      model of female mice. We also indicated that chronic treatment with pioglitazone
      (10 and 20mg/kg) increased clonic seizure latency in intraperitoneal
      pentylenetetrazole seizure model in female mice, while the incidence of tonic
      seizure and death remained unchanged. Ovariectomy abolished anti-seizure effect
      of pioglitazone in both seizure models of intravenous and intraperitoneal
      pentylenetetrazole. In conclusion, pioglitazone exerts anti-convulsant effect in
      both seizure models of intravenous and intraperitoneal pentylenetetrazole
      possibly through gonadal hormones of ovary in female mice. 

PMID- 26194062
TI  - The efficacy of uracil DNA glycosylase pretreatment in amplicon-based massively
      parallel sequencing with DNA extracted from archived formalin-fixed paraffin
      embedded esophageal cancer tissues.
AB  - Advances in mutation testing for molecular-targeted cancer therapies have led to
      the increased use of archived formalin-fixed paraffin-embedded (FFPE) tumors.
      However, DNA extracted from FFPE tumors (FFPE DNA) is problematic for mutation
      testing, especially for amplicon-based massively parallel sequencing (MPS), owing
      to DNA fragmentation and artificial C:G > T:A single nucleotide variants (SNVs)
      caused by deamination of cytosine to uracil. Therefore, to reduce artificial C:G
      > T:A SNVs in amplicon-based MPS using FFPE DNA, we evaluated the efficacy of
      uracil DNA glycosylase (UDG) pretreatment, which can eliminate uracil-containing
      DNA molecules, with 126 archived FFPE esophageal cancer specimens. We also
      examined the association between the frequency of C:G > T:A SNVs and DNA quality,
      as assessed by a quantitative PCR (qPCR)-based assay. UDG pretreatment
      significantly lowered the frequency of C:G > T:A SNVs in highly fragmented DNA
      (by approximately 60%). This effect was not observed for good- to moderate
      quality DNA, suggesting that a predictive assay (i.e., DNA quality assessment)
      needs to be performed prior to UDG pretreatment. These results suggest that UDG
      pretreatment is efficacious for mutation testing by amplicon-based MPS with
      fragmented DNA from FFPE samples. 

PMID- 26194063
TI  - [Switch of methoxy-polyethylene-glycol-epoetin beta to darbepoetin alfa in 263
      dialysis patients].
AB  - In early 2012, due to national supply disruption, the methoxy-polyethylene glycol
      epoetin beta (CERA) was no longer available and has been replaced by darbepoetin
      alfa (DA) in all dialysis patients. Official recommendations for the replacement
      of one by the other is missing or unclear. On this occasion, we wanted to examine
      how the shift from CERA to DA was done in terms of dose conversion factor and the
      other factors that could have influenced the dose of DA prescribed (hemoglobin,
      patient weight, dose of CERA). This retrospective multicenter open conducted in
      six dialysis centers in Alsace is the first large study (n=263) that evaluated
      the switch from CERA to DA in all chronic hemodialysis patients. We found that
      the instantaneous ratio of dose adjustment is close to 1 and that nephrologists
      are mainly based on the dose of CERA for determining the DA dose, before
      hemoglobin and weight. However, establishing a true dose-response ratio between
      the two molecules requires a long term prospective study. 

PMID- 26194064
TI  - Traditional and novel aspects of the metabolic actions of growth hormone.
AB  - Growth hormone has been known to be diabetogenic for almost a century and it's
      diabetogenic properties fostered consideration of excessive and abnormal GH
      secretion as a cause of diabetes, as well as a role in the microvascular
      complications, especially retinopathy. However, besides inducing insulin
      resistance, GH also is lipolytic and a major anabolic hormone for nitrogen
      retention and protein synthesis. These actions are best illustrated at the
      extremes of GH secretion: Gigantism/acromegaly is characterized by excessive
      growth, CHO intolerance, hyperplasia of bone, little body fat and prominent
      muscle development, whereas total deficiency of GH secretion or action is
      associated with adiposity, poor growth, and poor muscle development. These
      actions also become apparent during puberty and pregnancy, times when GH
      secretion is increased and account for the characteristic changes in body
      composition and tendency to diabetes. More recently, tissue specific deletions of
      the GH receptor (GHR), have uncovered newer metabolic effects including it's
      essential role in triglyceride export from the liver when GHR is deleted in the
      liver, leading to hepatic steatosis and ultimately to hepatic adenoma formation,
      effects which may explain these findings in obesity, a state of diminished GH
      secretion and action. In addition deletion of GH action in muscle and fat is
      associated with specific patterns of disturbed phenotype and metabolic effects in
      CHO, fat, and protein metabolism affecting the specific tissue and whole body
      function. This chapter provides an overview of these classic and newer metabolic
      functions of GH, placing this hormone and its actions in a central role of body
      fuel economy in health and disease.

PMID- 26194065
TI  - PPARalpha/gamma agonists and antagonists differently affect hepatic lipid
      metabolism, oxidative stress and inflammatory cytokine production in
      steatohepatitic rats.
AB  - Peroxisome proliferator-activated receptor (PPAR) alpha/gamma may control lipid
      metabolism and inflammatory response by regulating the downstream target genes,
      and play a crucial role in the process of non-alcoholic steatohepatitis (NASH)
      formation, but the difference and interaction between PPARalpha and PPARgamma are
      poorly understood. The rat model with NASH was established by orally feeding high
      fat and high-sucrose emulsion for 6weeks. The results shown that after the model
      rats were simultaneously treated with PPARalpha/gamma agonists, the total
      cholesterol (TC), triglyceride (TG) and inflammatory cytokine levels in serum and
      hepatic tissue, the hepatic steatosis and inflammatory cellular infiltration were
      decreased, and were consistent with the results of hepatic lipogenic gene and
      nuclear factor (NF)-kappaB protein expressions. Conversely, these indexes were
      increased by PPARalpha/gamma antagonist treatment. Compared with the model group,
      the serum free fatty acid (FFA) level was increased in the PPARalpha agonist
      treated group, decreased in the PPARgamma agonist-treated group, and unchanged in
      the PPARalpha/gamma agonists-treated group. The hepatic FFA level was low in the
      PPARalpha/gamma agonists-treated groups, but no significant variation in the
      PPARalpha/gamma antagonists-treated groups. The increments of hepatic reduced
      glutathione (GSH) and superoxide dismutase (SOD) contents in the PPARalpha/gamma
      agonists-treated groups were accompanied by decreased hepatic malondialdehyde
      (MDA) content. These findings demonstrated that PPARalpha/gamma activation might
      decrease the hepatic lipid accumulation, oxidative stress and inflammatory
      cytokine production, and PPARgamma could counterbalance the adverse effect of
      PPARalpha on circulating FFA. It was concluded that the integrative application
      of PPARalpha and PPARgamma agonists might exert a synergic inhibitory effect on
      NASH formation through the modulation of PPARalpha/gamma-mediated lipogenic and
      inflammatory gene expressions.

PMID- 26194066
TI  - House dust mite allergen Der f 1 induces IL-8 in human basophilic cells via ROS
      ERK and p38 signal pathways.
AB  - Der f 1, a major house dust mite allergen and member of the papain-like cysteine
      protease family, can provoke immune responses with its proteolytic activity. To
      understand the role of Der f 1 in inflammatory immune responses, we studied the
      mechanism of the regulation of interleukin (IL)-8 expressions in human basophilic
      cell KU812 by proteolytically active recombinant Der f 1. Not only production of
      IL-8 mRNA was induced but also the DNA binding activity of activator protein-1
      (AP-1) and phosphorylation of NF-kappaB p65 were increased in Der f 1-treated
      KU812. Furthermore, Der f 1 induction of IL-8 expression was sensitive to
      pharmacological inhibition of ERK and p38 mitogen activated protein kinase (MAPK)
      pathways. Der f 1 also activated ERK and p38 MAPK phosphorylation and rapidly
      induced reactive oxygen species (ROS) production. The antioxidant N-acetyl
      cysteine (NAC) inhibited phosphorylation of ERK, but not p38, suggesting that
      secretion of IL-8 in KU812 cells treated with Der f 1 is dependent on ROS, ERK
      MAPK and p38 MAPK. We describe the mechanism of Der f 1-induced IL-8 secretion
      from human basophilic cells, which are thought to be important for allergic
      inflammation independent of IgE antibodies. These findings improve our
      understanding of the inflammatory immune response in human basophils to protease
      allergens. 

PMID- 26194068
TI  - Flexible band gap tuning of hexagonal boron nitride sheets interconnected by
      acetylenic bonds.
AB  - The energetic and electronic properties of acetylenic-bond-interconnected
      hexagonal boron nitride sheets (BNyne), in which the number of rows of BN
      hexagonal rings (denoted as BN width) between neighboring arrays of acetylenic
      linkages increases consecutively, have been explored using first-principles
      calculations. Depending on the spatial position of B/N atoms with respect to the
      acetylenic linkages, there are two different types of configurations. The band
      structure features and band gap evolutions of BNyne structures as a function of
      the BN width can be categorized into two families, corresponding to two distinct
      types of configurations. In particular, for both types of BNyne structures, the
      band gap variations exhibit odd-even oscillating behavior depending on the BN
      width, which is related to the different symmetries of acetylenic chains in the
      unit cell. These results suggest that the embedded linear acetylenic chains can
      provide more flexibility for manipulation of the atomic and electronic properties
      of hexagonal boron nitride. These sp-sp(2) hybrid structures might promise
      importantly potential applications for developing nanoscale electronic and
      optoelectronic devices. 

PMID- 26194069
TI  - Identifiability of PBPK models with applications to dimethylarsinic acid
      exposure.
AB  - Any statistical model should be identifiable in order for estimates and tests
      using it to be meaningful. We consider statistical analysis of physiologically
      based pharmacokinetic (PBPK) models in which parameters cannot be estimated
      precisely from available data, and discuss different types of identifiability
      that occur in PBPK models and give reasons why they occur. We particularly focus
      on how the mathematical structure of a PBPK model and lack of appropriate data
      can lead to statistical models in which it is impossible to estimate at least
      some parameters precisely. Methods are reviewed which can determine whether a
      purely linear PBPK model is globally identifiable. We propose a theorem which
      determines when identifiability at a set of finite and specific values of the
      mathematical PBPK model (global discete identifiability) implies identifiability
      of the statistical model. However, we are unable to establish conditions that
      imply global discrete identifiability, and conclude that the only safe approach
      to analysis of PBPK models involves Bayesian analysis with truncated priors.
      Finally, computational issues regarding posterior simulations of PBPK models are
      discussed. The methodology is very general and can be applied to numerous PBPK
      models which can be expressed as linear time-invariant systems. A real data set
      of a PBPK model for exposure to dimethyl arsinic acid (DMA(V)) is presented to
      illustrate the proposed methodology. 

PMID- 26194067
TI  - IL-1 family members in the pathogenesis and treatment of metabolic disease: Focus
      on adipose tissue inflammation and insulin resistance.
AB  - Obesity is characterized by a chronic, low-grade inflammation that contributes to
      the development of insulin resistance and type 2 diabetes. Cytokines and
      chemokines produced by immunocompetent cells influence local as well as systemic
      inflammation and are therefore critical contributors to the pathogenesis of type
      2 diabetes. Hence, cytokines that modulate inflammatory responses are emerging as
      potential targets for intervention and treatment of the metabolic consequences of
      obesity. The interleukin-1 (IL-1) family of cytokines and receptors are key
      mediators of innate inflammatory responses and exhibit both pro- and anti
      inflammatory functions. During the last decades, mechanistic insights into how
      the IL-1 family affects the initiation and progression of obesity-induced insulin
      resistance have increased significantly. Here, we review the current knowledge
      and understanding, with emphasis on the therapeutic potential of individual
      members of the IL-1 family of cytokines for improving insulin sensitivity in
      patients with diabetes. 

PMID- 26194070
TI  - Baccharis dracunculifolia methanol extract enhances glucose-stimulated insulin
      secretion in pancreatic islets of monosodium glutamate induced-obesity model
      rats.
AB  - CONTEXT: Obesity is the main risk factor for type 2 diabetes mellitus. Secondary
      metabolites with biological activities and pharmacological potential have been
      identified in species of the Baccharis genus that are specifically distributed in
      the Americas. OBJECTIVE: This study evaluated the effects of methanol extracts
      from Baccharis dracunculifolia DC. Asteraceae on metabolic parameters, satiety,
      and growth in monosodium glutamate (MSG) induced-obesity model rats. MATERIALS
      AND METHODS: MSG was administered to 32 newborn rats (4 mg/g of body weight) once
      daily for 5 consecutive days. Four experimental groups (control, control +
      extract, MSG, and MSG + extract) were treated for 30 consecutive days with 400
      mg/kg of B. dracunculifolia extract by gavage. Biochemical parameters,
      antioxidant activity, total extract phenolic content (methanolic, ethanolic, and
      acetone extractions), and pancreatic islets were evaluated. RESULTS: High levels
      of phenolic compounds were identified in B. dracunculifolia extracts (methanol:
      46.2 +/- 0.4 mg GAE/L; acetate: 70.5 +/- 0.5 mg GAE/L; and ethanol: 30.3 +/- 0.21
      mg GAE/L); high antioxidant activity was detected in B. dracunculifolia ethanol
      and methanol extracts. The concentration of serum insulin increased 30% in obese
      animals treated with extract solutions (1.4-2.0 uU/mL, p < 0.05). Insulin
      secretion in pancreatic islets was 8.3 mM glucose (58%, p < 0.05) and 16.7 mM
      (99.5%, p < 0.05) in rats in the MSG + extract and MSG groups, respectively.
      DISCUSSION AND CONCLUSION: Treatment with B. dracunculifolia extracts protected
      pancreatic islets and prevented the irreversible cellular damage observed in
      animals in obesity and diabetes models.

PMID- 26194071
TI  - Mitochondrial Energy Metabolism and Thyroid Cancers.
AB  - Primary thyroid cancers including papillary, follicular, poorly differentiated,
      and anaplastic carcinomas show substantial differences in biological and clinical
      behaviors. Even in the same pathological type, there is wide variability in the
      clinical course of disease progression. The molecular carcinogenesis of thyroid
      cancer has advanced tremendously in the last decade. However, specific inhibition
      of oncogenic pathways did not provide a significant survival benefit in advanced
      progressive thyroid cancer that is resistant to radioactive iodine therapy.
      Accumulating evidence clearly shows that cellular energy metabolism, which is
      controlled by oncogenes and other tumor-related factors, is a critical factor
      determining the clinical phenotypes of cancer. However, the role and nature of
      energy metabolism in thyroid cancer remain unclear. In this article, we discuss
      the role of cellular energy metabolism, particularly mitochondrial energy
      metabolism, in thyroid cancer. Determining the molecular nature of metabolic
      remodeling in thyroid cancer may provide new biomarkers and therapeutic targets
      that may be useful in the management of refractory thyroid cancers. 

PMID- 26194073
TI  - Trends in the Diabetes Epidemic in Korea.
AB  - Diabetes mellitus is a leading cause of mortality and increased disability
      adjusted life years worldwide. In Korea, the prevalence of diabetes increased
      from 8.6% to 11.0% in 2001 to 2013 and the prevalence of adult obesity, which is
      the most important risk factor of diabetes, increased from 29.2% to 31.8% during
      the same period. There has been a dramatic increase in the number of obese
      Koreans with diabetes in recent decades and the prevalence of diabetes in people
      aged 40 years and older also increased in 2001 to 2013. Nevertheless, the mean
      age at the first diagnosis of diabetes was very similar for men in 2005 and 2013,
      while the mean age for women decreased slightly. There is an inverse linear
      relationship between body mass index and age at the diagnosis of diabetes among
      those who are newly diagnosed. Accordingly, the prevalence of diabetes is
      increasingly shifting to younger individuals and those who are obese. Therefore,
      public efforts should focus on healthy lifestyle changes, primary prevention
      measures, screening for the early detection of diabetes, and long-term
      management. 

PMID- 26194074
TI  - Genetic Studies on Diabetic Microvascular Complications: Focusing on Genome-Wide
      Association Studies.
AB  - Diabetes is a common metabolic disorder with a worldwide prevalence of 8.3% and
      is the leading cause of visual loss, end-stage renal disease and amputation.
      Recently, genome-wide association studies (GWASs) have identified genetic risk
      factors for diabetic microvascular complications of retinopathy, nephropathy, and
      neuropathy. We summarized the recent findings of GWASs on diabetic microvascular
      complications and highlighted the challenges and our opinion on future
      directives. Five GWASs were conducted on diabetic retinopathy, nine on
      nephropathy, and one on neuropathic pain. The majority of recent GWASs were
      underpowered and heterogeneous in terms of study design, inclusion criteria and
      phenotype definition. Therefore, few reached the genome-wide significance
      threshold and the findings were inconsistent across the studies. Recent GWASs
      provided novel information on genetic risk factors and the possible
      pathophysiology of diabetic microvascular complications. However, further
      collaborative efforts to standardize phenotype definition and increase sample
      size are necessary for successful genetic studies on diabetic microvascular
      complications. 

PMID- 26194072
TI  - Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders.
AB  - Kisspeptin has recently emerged as a key regulator of the mammalian reproductive
      axis. It is known that kisspeptin, acting centrally via the kisspeptin receptor,
      stimulates secretion of gonadotrophin releasing hormone (GnRH). Loss of
      kisspeptin signaling causes hypogonadotrophic hypogonadism in humans and other
      mammals. Kisspeptin interacts with other neuropeptides such as neurokinin B and
      dynorphin, to regulate GnRH pulse generation. In addition, a growing body of
      evidence suggests that kisspeptin signaling be regulated by nutritional status
      and stress. Kisspeptin may also represent a novel potential therapeutic target in
      the treatment of fertility disorders. Early human studies suggest that peripheral
      exogenous kisspeptin administration stimulates gonadotrophin release in healthy
      adults and in patients with certain forms of infertility. This review aims to
      concisely summarize what is known about kisspeptin as a regulator of reproductive
      function, and provide an update on recent advances within this field. 

PMID- 26194075
TI  - New Directions in Chronic Disease Management.
AB  - A worldwide epidemic of chronic disease, and complications thereof, is underway,
      with no sign of abatement. Healthcare costs have increased tremendously,
      principally because of the need to treat chronic complications of non
      communicable diseases including cardiovascular disease, blindness, end-stage
      renal disease, and amputation of extremities. Current healthcare systems fail to
      provide an appropriate quality of care to prevent the development of chronic
      complications without additional healthcare costs. A new paradigm for prevention
      and treatment of chronic disease and the complications thereof is urgently
      required. Several clinical studies have clearly shown that frequent communication
      between physicians and patients, based on electronic data transmission from
      medical devices, greatly assists in the management of chronic disease. However,
      for various reasons, these advantages have not translated effectively into real
      clinical practice. In the present review, we describe current relevant studies,
      and trends in the use of information technology for chronic disease management.
      We also discuss limitations and future directions. 

PMID- 26194076
TI  - Clinical Implications of Glucose Variability: Chronic Complications of Diabetes.
AB  - Glucose variability has been identified as a potential risk factor for diabetic
      complications; oxidative stress is widely regarded as the mechanism by which
      glycemic variability induces diabetic complications. However, there remains no
      generally accepted gold standard for assessing glucose variability.
      Representative indices for measuring intraday variability include calculation of
      the standard deviation along with the mean amplitude of glycemic excursions
      (MAGE). MAGE is used to measure major intraday excursions and is easily measured
      using continuous glucose monitoring systems. Despite a lack of randomized
      controlled trials, recent clinical data suggest that long-term glycemic
      variability, as determined by variability in hemoglobin A1c, may contribute to
      the development of microvascular complications. Intraday glycemic variability is
      also suggested to accelerate coronary artery disease in high-risk patients. 

PMID- 26194077
TI  - Adipokine Profiles and Metabolic Health.

PMID- 26194078
TI  - Exendin-4 Inhibits the Expression of SEPP1 and Fetuin-A via Improvement of
      Palmitic Acid-Induced Endoplasmic Reticulum Stress by AMPK.
AB  - BACKGROUND: Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived
      glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty
      liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1
      receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is
      unknown. METHODS: The human hepatoma cell line HepG2 was treated with palmitic
      acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100
      nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and
      endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated
      using quantitative real-time reverse transcription polymerase chain reaction and
      Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK)
      small interfering RNA (siRNA) was performed to establish the effect of exendin-4
      mediated AMPK in the regulation of SEPP1 and fetuin-A expression. RESULTS:
      Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers
      including PKR-like ER kinase, inositol-requiring kinase 1alpha, activating
      transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4
      also reduced the expression of SEPP1 and fetuin-A in cells treated with
      tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5
      aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic
      SEPP1 and fetuin-A were negatively related by AMPK, which is the target of
      exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A
      expression in cells transfected with AMPK siRNA. CONCLUSION: These data suggest
      that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via
      improvement of PA-induced ER stress by AMPK.

PMID- 26194079
TI  - Anaplastic Thyroid Cancer: Experience of the Philippine General Hospital.
AB  - BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare type of thyroid malignancy
      and one of the most aggressive solid tumors, responsible for between 14% and 50%
      of the total annual mortality associated with thyroid cancer. METHODS: A
      retrospective study was made of all ATC cases diagnosed by biopsy in the
      Philippine General Hospital between 2008 and 2013. RESULTS: A total of 15
      patients were identified, with a median age at diagnosis of 63 years. All tumors
      were at least 6 cm in size upon diagnosis. All patients had a previous history of
      thyroid pathology, presenting with an average duration of 11 years. Eleven
      patients presented with cervical lymphadenopathies, whereas seven exhibited signs
      of distant metastases, for which the lungs appeared to be the most common site.
      More than 70% of the patients presented with a rapidly growing neck mass, leading
      to airway obstruction. Only three patients were treated using curative surgery;
      the majority received palliative and supportive forms of treatment. In addition,
      only three patients were offered radiotherapy. Chemotherapy was not offered to
      any patient. Only two patients were confirmed to still be alive during the study
      period. The median survival time for the other patients was 3 months; in the
      majority of cases the patient died within the first year following diagnosis.
      CONCLUSION: Our experience with ATC demonstrated concordance with other
      institutions with respect to current clinical profile, presentation, and
      prognosis. An absence of distant metastases and lymph node involvement was
      associated with improved survival outcomes, whereas age at diagnosis and tumor
      size did not affect survival. Curative surgery offers the most effective means of
      prolonging survival. Radiotherapy and chemotherapy in combination with surgery
      represents a promising treatment strategy.

PMID- 26194080
TI  - Apolipoprotein B Is Related to Metabolic Syndrome Independently of Low Density
      Lipoprotein Cholesterol in Patients with Type 2 Diabetes.
AB  - BACKGROUND: Increased low density lipoprotein cholesterol (LDL-C) level and the
      presence of metabolic syndrome (MetS) are important risk factors for
      cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Recent studies
      demonstrated apolipoprotein B (apoB), a protein mainly located in LDL-C, was an
      independent predictor of the development of CVD especially in patients with T2DM.
      The aim of this study was to investigate the relationship between apoB and MetS
      in T2DM patients. METHODS: We analyzed 912 patients with T2DM. Fasting blood
      samples were taken for glycated hemoglobin, high-sensitivity C-reactive protein,
      total cholesterol, triglyceride (TG), high density lipoprotein cholesterol, LDL
      C, and apoB. MetS was defined by the modified National Cholesterol Education
      Program Adult Treatment Panel III criteria. We performed a hierarchical
      regression analysis with apoB as the dependent variable. Age, sex, the number of
      components of MetS and LDL-C were entered at model 1, the use of lipid-lowering
      medications at model 2, and the individual components of MetS were added at model
      3. RESULTS: Seventy percent of total subjects had MetS. ApoB level was higher in
      subjects with than those without MetS (104.5+/-53.3 mg/dL vs. 87.7+/-33.7 mg/dL,
      P<0.01) even after adjusting for LDL-C. ApoB and LDL-C were positively correlated
      to the number of MetS components. The hierarchical regression analysis showed
      that the increasing number of MetS components was associated with higher level of
      apoB at step 1 and step 2 (beta=0.120, P<0.001 and beta=0.110, P<0.001,
      respectively). At step 3, TG (beta=0.116, P<0.001) and systolic blood pressure
      (beta=0.099, P<0.05) were found to significantly contribute to apoB. CONCLUSION:
      In patients with T2DM, apoB is significantly related to MetS independently of LDL
      C level. Of the components of MetS, TG, and systolic blood pressure appeared to
      be determinants of apoB.

PMID- 26194081
TI  - Glucagon-Like Peptide-1 Increases Mitochondrial Biogenesis and Function in INS-1
      Rat Insulinoma Cells.
AB  - Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that increases
      glucose-stimulated insulin secretion in pancreatic beta-cells. Since
      mitochondrial function is crucial to insulin secretion, we hypothesized that GLP
      1 may increase mitochondrial biogenesis in pancreatic beta-cells. We treated INS
      1 rat insulinoma cells with GLP-1 or exendin-4 for 48 hours and measured
      mitochondrial mass and function. Both GLP-1 and exendin-4 increased mitochondrial
      mass by approximately 20%. The mitochondria/cytosol ratio was increased from
      7.60+/-3.12% to 10.53+/-2.70% by exendin-4. In addition, GLP-1 increased the
      mitochondrial membrane potential and oxygen consumption. Proliferator-activated
      receptor-gamma coactivator 1alpha expression was increased approximately 2-fold
      by GLP-1 treatment. In conclusion, the present study presents evidence for a new
      mechanism of action by which GLP-1 improves pancreatic beta-cell function via
      enhanced mitochondrial mass and performance. 

PMID- 26194082
TI  - Letter: Expression of Glucagon-Like Peptide-1 Receptor in Papillary Thyroid
      Carcinoma and Its Clinicopathologic Significance (Endocrinol Metab 2014;29:536
      44, Min Jung Jung et al.).

PMID- 26194083
TI  - Response: Expression of Glucagon-Like Peptide-1 Receptor in Papillary Thyroid
      Carcinoma and Its Clinicopathologic Significance (Endocrinol Metab 2014;29:536
      44, Min Jung Jung et al.).

PMID- 26194084
TI  - Projected CAP/SAC-CI method with smooth Voronoi potential for calculating
      resonance states.
AB  - The complex absorbing potential (CAP)/symmetry-adapted cluster-configuration
      interaction (SAC-CI) method has been combined with a smooth Voronoi potential,
      which was recently introduced in the extrapolation procedure, to locate pi*
      resonance states of small- to medium-size molecules. Here, the projected CAP/SAC
      CI method is combined with this potential and used to calculate the double-bond
      and heteroaromatic pi* resonances of acetaldehyde, butadiene, glyoxal, pyridine,
      pyrazine, and furan. As observed in the pilot applications, the corrected eta
      trajectories provide a stable resonance energy and width or lifetime regardless
      of the size parameter (rcut ) of the smooth Voronoi potential. However, in
      general, the stabilization behavior of the trajectories is clearer for larger
      rcut values, which implies that the interaction of the CAP with the valence
      electrons is more advantageously addressed by a larger "cavity" size.

PMID- 26194085
TI  - Incidence of syphilis in Greenland 2010-2014: the beginning of a new epidemic?
AB  - OBJECTIVE: To estimate the incidence of syphilis from 2010 to 2014 and to assess
      whether contact tracing has been performed. STUDY DESIGN: Observational cross
      sectional study. METHOD: Data on reported cases were collected from the national
      register of the chief medical officer in Greenland. Unreported cases were found
      by searching the electronic medical record system for patients who had received
      an electronic prescription of benzathine penicillin, doxycycline or tetracycline.
      Medical records were reviewed to verify the diagnosis of syphilis and to evaluate
      if contact tracing had been performed. RESULTS: Ninety-four cases of syphilis (51
      males and 43 females) with a median age of 27 years (20-40) were included. The
      incidence of syphilis in Greenland has increased from zero cases in 2010 to 95.7
      per 100,000 inhabitants in 2014 affecting mainly young people. Contact tracing
      was performed in 80.9% (76/94) of the cases. CONCLUSION: Syphilis has re-occurred
      in Greenland and a new epidemic may be underway. Sustained awareness of
      treatment, contact tracing, monitoring and preventive initiatives are desirable.

PMID- 26194086
TI  - Comparative morphology of the oocyte surface and early development in four
      characiformes from the Sao Francisco River, Brazil.
AB  - Early development from the egg fertilization to complete resorption of the yolk
      sac is a critical period in the life cycle of teleost fish. Knowledge of this
      process provides essential parameters for aquaculture and identification of
      spawning sites in the wild. In the present study, a comparative morphological
      analysis of the oocyte surface as well as early development was performed in four
      commercially valuable species from the Sao Francisco River: Brycon orthotaenia,
      Leporinus obtusidens, Prochilodus argenteus, and Salminus franciscanus. Stripped
      oocytes, embryo, and yolk-sac larvae were analyzed by scanning electron
      microscopy (SEM) and histology. A set of 10 lectins was used for investigation of
      lectin-binding pattern in oocytes. In the four species, the outer layer of the
      zona radiata reacted to most lectins, indicating complex polysaccharides at the
      oocyte surface while no reactivity was detected in the inner zona radiata and
      yolk globules. Typical structural arrangements were recognized at the micropylar
      region by SEM. The four species showed nonadhesive eggs, short embryonic period
      (18-20 h at 24 +/- 1 degrees C), and poorly developed larvae at hatching. At 24 h
      posthatching (hph), larvae of the four species had neuromasts on the body
      surface. Rudimentary cement glands for larval attachment were identified on the
      cephalic region at 24 and 48 hph in B. orthotaenia and S. franciscanus, and
      following they were in regression. The time for whole yolk resorption varied
      among species from 48 to 120 hph, occurring earlier in S. franciscanus, followed
      by B. orthotaenia, P. argenteus, and L. obtusidens. The formation of the
      digestive tract and the mouth opening indicated initiation of exogenous feeding
      24 h before complete resorption of the yolk. Together, our data indicate
      similarities in the early development among species that may be related to the
      life cycle strategies and phylogeny.

PMID- 26194087
TI  - Characterization of Heronamide Biosynthesis Reveals a Tailoring Hydroxylase and
      Indicates Migrated Double Bonds.
AB  - Heronamides belong to a growing family of beta-amino acid polyketide macrolactams
      (betaPMs) with an unsaturated side chain. The biosynthetic gene cluster for
      heronamide F was identified from the deep-sea-derived Streptomyces sp. SCSIO
      03032. The involvement of the gene cluster in heronamide biosynthesis was
      confirmed by the functional characterization of the P450 enzyme HerO as an 8
      hydroxylase for tailoring heronamide biosynthesis. The presence of migrated
      double bonds in the conjugated diene-containing side chain of heronamides was
      confirmed by feeding experiments with labeled small carboxylic acid molecules.
      This study is the first demonstration of migrated double bonds in betaPMs with an
      unsaturated side chain. 

PMID- 26194088
TI  - Anomalous Stagewise Lithiation of Gold-Coated Silicon Nanowires: A Combined In
      Situ Characterization and First-Principles Study.
AB  - Through a combined density functional theory and in situ scanning electron
      microscopy study, the effects of presence of gold (Au) spreading on the
      lithiation process of silicon nanowire (SiNW) were systematically examined.
      Different from a pristine SiNW, an Au-coated SiNW (Au-SiNW) is lithiated in three
      distinct stages; Li atoms are found to be incorporated preferentially in the Au
      shell, whereas the thin AuSi interface layer may serve as a facile diffusion path
      along the nanowire axial direction, followed by the prompt lithiation of the Si
      core in the radial direction. The underlying mechanism of the intriguing
      stagewise lithiation behavior is explained through our theoretical analysis,
      which appears well-aligned with the experimental evidence. 

PMID- 26194089
TI  - Metallic Nanoparticle (TiO2 and Fe3O4) Application Modifies Rhizosphere
      Phosphorus Availability and Uptake by Lactuca sativa.
AB  - Application of engineered nanoparticles (NPs) with respect to nutrient uptake in
      plants is not yet well understood. The impacts of TiO2 and Fe3O4 NPs on the
      availability of naturally soil-bound inorganic phosphorus (Pi) to plants were
      studied along with relevant parameters. For this purpose, Lactuca sativa
      (lettuce) was cultivated on the soil amended with TiO2 and Fe3O4 (0, 50, 100,
      150, 200, and 250 mg kg(-1)) over a period of 90 days. Different techniques, such
      as scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy
      (EDX), Raman, and Fourier transform infrared spectroscopy (FTIR) were used to
      monitor translocation and understand the possible mechanisms for phosphorus (P)
      uptake. The trends for P accumulation were different for roots (TiO2 > Fe3O4 >
      control) and shoots (Fe3O4 > TiO2 > control). Cystine and methionine were
      detected in the rhizosphere in Raman spectra. Affinities of NPs to adsorb
      phosphate ions, modifications in P speciation, and NP stress in the rhizosphere
      had possibly contributed to enhanced root exudation and acidification. All of
      these changes led to improved P availability and uptake by the plants. These
      promising results can help to develop an innovative strategy for using NPs for
      improved nutrient management to ensure food security. 

PMID- 26194090
TI  - Cucurbit[8]uril-templated H and J dimers of bichromophoric coumarin dyes: origin
      of contrasting emission.
AB  - We report the supramolecular control and mechanism for the contrasting dimer
      emission from selected bichromophoric coumarin dyes caught in the cucurbit[8]uril
      cavity-a facile approach to developing photo-responsive molecular assemblies
      through structural tuning. 

PMID- 26194094
TI  - An active atmospheric methane sink in high Arctic mineral cryosols.

PMID- 26194091
TI  - Childhood acute lymphoblastic leukemia: Integrating genomics into therapy.
AB  - Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a
      genetically complex entity that remains a major cause of childhood cancer-related
      mortality. Major advances in genomic and epigenomic profiling during the past
      decade have appreciably enhanced knowledge of the biology of de novo and relapsed
      ALL and have facilitated more precise risk stratification of patients. These
      achievements have also provided critical insights regarding potentially
      targetable lesions for the development of new therapeutic approaches in the era
      of precision medicine. In this review, the authors delineate the current genetic
      landscape of childhood ALL, emphasizing patient outcomes with contemporary
      treatment regimens as well as therapeutic implications of newly identified
      genomic alterations in specific subsets of ALL.

PMID- 26194093
TI  - Protection against beta-amyloid-induced synaptic and memory impairments via
      altering beta-amyloid assembly by bis(heptyl)-cognitin.
AB  - beta-amyloid (Abeta) oligomers have been closely implicated in the pathogenesis
      of Alzheimer's disease (AD). We found, for the first time, that bis(heptyl)
      cognitin, a novel dimeric acetylcholinesterase (AChE) inhibitor derived from
      tacrine, prevented Abeta oligomers-induced inhibition of long-term potentiation
      (LTP) at concentrations that did not interfere with normal LTP. Bis(heptyl)
      cognitin also prevented Abeta oligomers-induced synaptotoxicity in primary
      hippocampal neurons. In contrast, tacrine and donepezil, typical AChE inhibitors,
      could not prevent synaptic impairments in these models, indicating that the
      modification of Abeta oligomers toxicity by bis(heptyl)-cognitin might be
      attributed to a mechanism other than AChE inhibition. Studies by using dot
      blotting, immunoblotting, circular dichroism spectroscopy, and transmission
      electron microscopy have shown that bis(heptyl)-cognitin altered Abeta assembly
      via directly inhibiting Abeta oligomers formation and reducing the amount of
      preformed Abeta oligomers. Molecular docking analysis further suggested that
      bis(heptyl)-cognitin presumably interacted with the hydrophobic pockets of Abeta,
      which confers stabilizing powers and assembly alteration effects on Abeta. Most
      importantly, bis(heptyl)-cognitin significantly reduced cognitive impairments
      induced by intra-hippocampal infusion of Abeta oligomers in mice. These results
      clearly demonstrated how dimeric agents prevent Abeta oligomers-induced synaptic
      and memory impairments, and offered a strong support for the beneficial
      therapeutic effects of bis(heptyl)-cognitin in the treatment of AD. 

PMID- 26194095
TI  - Functional genomics identifies negative regulatory nodes controlling phagocyte
      oxidative burst.
AB  - The phagocyte oxidative burst, mediated by Nox2 NADPH oxidase-derived reactive
      oxygen species, confers host defense against a broad spectrum of bacterial and
      fungal pathogens. Loss-of-function mutations that impair function of the Nox2
      complex result in a life-threatening immunodeficiency, and genetic variants of
      Nox2 subunits have been implicated in pathogenesis of inflammatory bowel disease
      (IBD). Thus, alterations in the oxidative burst can profoundly impact host
      defense, yet little is known about regulatory mechanisms that fine-tune this
      response. Here we report the discovery of regulatory nodes controlling oxidative
      burst by functional screening of genes within loci linked to human inflammatory
      disease. Implementing a multi-omics approach, we define transcriptional,
      metabolic and ubiquitin-cycling nodes controlled by Rbpj, Pfkl and Rnf145,
      respectively. Furthermore, we implicate Rnf145 in proteostasis of the Nox2
      complex by endoplasmic reticulum-associated degradation. Consequently, ablation
      of Rnf145 in murine macrophages enhances bacterial clearance, and rescues the
      oxidative burst defects associated with Ncf4 haploinsufficiency. 

PMID- 26194096
TI  - Pretransplant malnutrition, inflammation, and atherosclerosis affect
      cardiovascular outcomes after kidney transplantation.
AB  - BACKGROUND: Malnutrition, inflammation, and atherosclerosis (MIA) syndrome is
      associated with a high mortality rate in patients with end-stage renal disease.
      However, the clinical relevance of MIA syndrome in kidney transplantation (KT)
      recipients remains unknown. METHODS: We enrolled 1348 adult KT recipients.
      Recipients were assessed based on serum albumin, cholesterol, or body mass index
      for the malnutrition factor and C-reactive protein level for the inflammation
      factor. Any history of cardiovascular (CV), cerebrovascular, or peripheral
      vascular disease satisfied the atherosclerosis factor. Each MIA factors were
      assessed by univariate analysis and we calculated an overall risk score by
      summing up scores for each independent variable. The enrolled patients were
      divided into 4 groups depending on the MIA score (0, 2-4, 6, 8-10). RESULTS: The
      patients with higher MIA score showed worse outcome of fatal/non-fatal acute
      coronary syndrome (ACS) (p < 0.001) and composite outcomes of ACS and all-cause
      mortality (p < 0.001) than with the lower MIA score. In multivariate analysis,
      ACS showed significantly higher incidence in the MIA score 8-10 group than in the
      MIA score 0 group (Hazard ratio 6.12 95 % Confidence interval 1.84-20.32 p =
      0.003). CONCLUSIONS: The presence of MIA factors before KT is an independent
      predictor of post-transplant CV outcomes.

PMID- 26194097
TI  - Clinicopathological characteristics of immunoglobulin G4-related sialadenitis.
AB  - INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized
      fibro-inflammatory condition. Forty-two cases with immunoglobulin G4-related
      sialadenitis (IgG4-RS) confirmed by histopathological and immunohistochemical
      assessment were studied to clarify the clinicopathologic characteristics of the
      salivary glands involved in IgG4-RS, especially the relationship between the
      histopathologic features and function of salivary glands or serum levels of IgG4.
      METHODS: Clinical, serologic, imaging and histopathological data of these cases
      were analyzed. CT volumes of submandibular, parotid, and lacrimal glands were
      calculated. The saliva flow rate was measured. Scintigraphy with 99mTc
      pertechnetate was undertaken in 31 cases, and the concentration index (CI) and
      secretion index (SI) was calculated. Relationships between fibrosis severity and
      salivary gland function or serum IgG4 levels were analyzed. RESULTS: The first
      symptom was swelling of bilateral submandibular or lacrimal glands. Physical
      examination showed multiple bilateral major salivary glands (including sublingual
      and accessory parotid glands) and lacrimal glands were enlarged in IgG4 RS.
      Multiple enlarged cervical lymph nodes were noted in 30 patients. Saliva flow at
      rest was lower than normal in 34 cases; stimulated saliva flow was lower than
      normal in 15 cases. Secretory function was reduced more severely in the
      submandibular glands than in the parotid glands. Serum levels of IgG4 were
      elevated in 95.2% of cases and 78.6% patients had increased IgE levels. Serum
      IgG4 level was higher and saliva secretion lower as glandular fibrosis increased.
      CONCLUSIONS: Prominent changes in the morphology, histology, immunohistochemistry
      and secretion of the major salivary glands of IgG4-RS patients were accompanied
      by involvement of the lacrimal glands and cervical lymph nodes. Elevated IgE,
      allergic history, eosinophil infiltration suggest allergic reactions as a
      potential pathogenesis of IgG4-RS. Severity of glandular fibrosis correlated with
      salivary function and serum levels of IgG4.

PMID- 26194098
TI  - PCDD and PCDF exposures among fishing community through intake of fish and
      shellfish from the Straits of Malacca.
AB  - BACKGROUND: Exposure to PCDD/PCDF (dioxin and furan) through consumption of fish
      and shellfish is closely related to the occurrence of skin diseases, such as
      chloracne and hyperpigmentation. This study aimed to determine the exposure of
      PCDD/PCDF and its congeners in fish and shellfish obtained from different regions
      of the Straits of Malacca among the fishing community. METHODS: The risk of fish
      and shellfish consumption and exposure to PCDD/PCDF among fishermen living in
      coastal areas of the Straits were evaluated based on a cross-sectional study
      involving face to face interviews, blood pressure and anthropometric
      measurements, and administration of food frequency questionnaires (FFQ). Skin
      examination was done by a dermatologist after the interview session.
      Determination of 17 congeners of PCDD/PCDF in 48 composite samples of fish and
      shellfish was performed based on HRGC/HRMS analysis. RESULTS: The total PCDD/PCDF
      in the seafood samples ranged from 0.12 to 1.24 pg WHO-TEQ/g fresh weight (4.6
      21.8 pg WHO-TEQ/g fat). No significant difference found for the concentrations of
      PCDD/PCDF between the same types of seafood samples obtained from the three
      different regions. The concentrations of the most potent congener, 2,3,7,8-TCDD
      in the seafood samples ranged from 0.01 to 0.11 pg WHO-TEQ/g FW (1.9 pg WHO-TEQ/g
      fat). A positive moderate correlation was found between the fat contents and
      concentrations of PCDD/PCDF determined in the seafood samples. The total
      PCDD/PCDF in all seafood samples were below the 1 pg WHO-TEQ/g fresh weight, with
      the exception of grey eel-catfish. The respondents had consumed fish and
      shellfish with the amounts ranging between 2.02 g and 44.06 g per person per day.
      The total PCDD/PCDF exposures through consumption of fish and shellfish among the
      respondents were between 0.01 and 0.16 pg WHO-TEQ/kg BW/day. With regard to the
      two PCDD/PCDF-related skin diseases, no chloracne case was found among the
      respondents, but 2.2% of the respondents were diagnosed to have
      hyperpigmentation. CONCLUSION: Intake of a moderate amount of fish and shellfish
      from the area is safe and does not pose a risk for skin diseases. An over
      consumption of seafood from the potentially polluted area of the Straits should
      be monitored in future.

PMID- 26194099
TI  - Airways resistance and specific conductance for the diagnosis of obstructive
      airways diseases.
AB  - BACKGROUND: Airway resistance (RAW) and specific airway conductance (sGAW) are
      measures that reflect the patency of airways. Little is known of the variability
      of these measures between different lung diseases. This study investigated the
      contribution of RAW and sGAW to a diagnosis of obstructive airways disease and
      their role in differentiating asthma from COPD. METHODS: 976 subjects admitted
      for the first time to a pulmonary practice in Belgium were included. Clinical
      diagnoses were based on complete pulmonary function tests and supported by
      investigations of physicians' discretion. 651 subjects had a final diagnosis of
      obstructive diseases, 168 had another respiratory disease and 157 subjects had no
      respiratory disease (healthy controls). RESULTS: RAW and sGAW were significantly
      different (p < 0.0001) between obstructive and other groups. Abnormal RAW and
      sGAW were found in 39 % and 18 % of the population, respectively, in which 81 %
      and 90 % had diagnosed airway obstruction. Multiple regression revealed sGAW to
      be a significant and independent predictor of an obstructive disorder. To
      differentiate asthma from COPD, RAW was found to be more relevant and
      statistically significant. In asthma patients with normal FEV1/FVC ratio, both
      RAW and sGAW were more specific than sensitive diagnostic tests in
      differentiating asthma from healthy subjects. CONCLUSIONS: RAW and sGAW are
      significant factors that contribute to the diagnosis and differentiation of
      obstructive airways diseases.

PMID- 26194100
TI  - Amplification of microsatellite repeat motifs is associated with the evolutionary
      differentiation and heterochromatinization of sex chromosomes in Sauropsida.
AB  - The sex chromosomes in Sauropsida (reptiles and birds) have evolved independently
      many times. They show astonishing diversity in morphology ranging from cryptic to
      highly differentiated sex chromosomes with male (XX/XY) and female heterogamety
      (ZZ/ZW). Comparing such diverse sex chromosome systems thus provides unparalleled
      opportunities to capture evolution of morphologically differentiated sex
      chromosomes in action. Here, we describe chromosomal mapping of 18 microsatellite
      repeat motifs in eight species of Sauropsida. More than two microsatellite repeat
      motifs were amplified on the sex-specific chromosome, W or Y, in five species
      (Bassiana duperreyi, Aprasia parapulchella, Notechis scutatus, Chelodina
      longicollis, and Gallus gallus) of which the sex-specific chromosomes were
      heteromorphic and heterochromatic. Motifs (AAGG)n and (ATCC)n were amplified on
      the W chromosome of Pogona vitticeps and the Y chromosome of Emydura macquarii,
      respectively. By contrast, no motifs were amplified on the W chromosome of
      Christinus marmoratus, which is not much differentiated from the Z chromosome.
      Taken together with previously published studies, our results suggest that the
      amplification of microsatellite repeats is tightly associated with the
      differentiation and heterochromatinization of sex-specific chromosomes in
      sauropsids as well as in other taxa. Although some motifs were common between the
      sex-specific chromosomes of multiple species, no correlation was observed between
      this commonality and the species phylogeny. Furthermore, comparative analysis of
      sex chromosome homology and chromosomal distribution of microsatellite repeats
      between two closely related chelid turtles, C. longicollis and E. macquarii,
      identified different ancestry and differentiation history. These suggest multiple
      evolutions of sex chromosomes in the Sauropsida. 

PMID- 26194101
TI  - Effect of species-specific differences in chromosome morphology on chromatin
      compaction and the frequency and distribution of RAD51 and MLH1 foci in two bovid
      species: cattle (Bos taurus) and the common eland (Taurotragus oryx).
AB  - Meiotic recombination between homologous chromosomes is crucial for their correct
      segregation into gametes and for generating diversity. We compared the frequency
      and distribution of MLH1 foci and RAD51 foci, synaptonemal complex (SC) length
      and DNA loop size in two related Bovidae species that share chromosome arm
      homology but show an extreme difference in their diploid chromosome number:
      cattle (Bos taurus, 2n = 60) and the common eland (Taurotragus oryx, 2nmale =
      31). Compared to cattle, significantly fewer MLH1 foci per cell were observed in
      the common eland, which can be attributed to the lower number of initial double
      strand breaks (DSBs) detected as RAD51 foci in leptonema. Despite the
      significantly shorter total autosomal SC length and longer DNA loop size of the
      common eland bi-armed chromosomes compared to those of bovine acrocentrics, the
      overall crossover density in the common eland was still lower than in cattle,
      probably due to the reduction in the number of MLH1 foci in the proximal regions
      of the bi-armed chromosomes. The formation of centric fusions during karyotype
      evolution of the common eland accompanied by meiotic chromatin compaction has
      greater implications in the reduction in the number of DSBs in leptonema than in
      the decrease of MLH1 foci number in pachynema. 

PMID- 26194103
TI  - Mapping a surgeon's becoming with Deleuze.
AB  - The process of 'becoming' shapes professionals' capability, confidence and
      identity. In contrast to notions of rugged individuals who achieve definitive
      status as experts, 'becoming' is a continuous emergent condition. It is often a
      process of struggle, and is always interminably linked to its environs and
      relationships. 'Becoming' is a way of understanding the tensions of everyday
      practice and knowledge of professionals. In this paper, we explore the notion of
      'becoming' from the perspective of surgeons. We suggest that 'becoming', as
      theorised by Deleuze, offers a more nuanced understanding than is often
      represented using conventional vocabularies of competence, error, quality and
      improvement. We develop this conception by drawing from our Deleuze-inspired
      study of mapping experience in surgery. We argue for Deleuzian mapping as a
      method to research health professionals' practice and experience, and suggest the
      utility of this approach as a pedagogical tool for medical education. 

PMID- 26194102
TI  - Evolution of selenophosphate synthetases: emergence and relocation of function
      through independent duplications and recurrent subfunctionalization.
AB  - Selenoproteins are proteins that incorporate selenocysteine (Sec), a nonstandard
      amino acid encoded by UGA, normally a stop codon. Sec synthesis requires the
      enzyme Selenophosphate synthetase (SPS or SelD), conserved in all prokaryotic and
      eukaryotic genomes encoding selenoproteins. Here, we study the evolutionary
      history of SPS genes, providing a map of selenoprotein function spanning the
      whole tree of life. SPS is itself a selenoprotein in many species, although
      functionally equivalent homologs that replace the Sec site with cysteine (Cys)
      are common. Many metazoans, however, possess SPS genes with substitutions other
      than Sec or Cys (collectively referred to as SPS1). Using complementation assays
      in fly mutants, we show that these genes share a common function, which appears
      to be distinct from the synthesis of selenophosphate carried out by the Sec- and
      Cys- SPS genes (termed SPS2), and unrelated to Sec synthesis. We show here that
      SPS1 genes originated through a number of independent gene duplications from an
      ancestral metazoan selenoprotein SPS2 gene that most likely already carried the
      SPS1 function. Thus, in SPS genes, parallel duplications and subsequent
      convergent subfunctionalization have resulted in the segregation to different
      loci of functions initially carried by a single gene. This evolutionary history
      constitutes a remarkable example of emergence and evolution of gene function,
      which we have been able to trace thanks to the singular features of SPS genes,
      wherein the amino acid at a single site determines unequivocally protein function
      and is intertwined to the evolutionary fate of the entire selenoproteome. 

PMID- 26194105
TI  - Automated Device for Asynchronous Extraction of RNA, DNA, or Protein Biomarkers
      from Surrogate Patient Samples.
AB  - Many biomarker-based diagnostic methods are inhibited by nontarget molecules in
      patient samples, necessitating biomarker extraction before detection. We have
      developed a simple device that purifies RNA, DNA, or protein biomarkers from
      complex biological samples without robotics or fluid pumping. The device design
      is based on functionalized magnetic beads, which capture biomarkers and remove
      background biomolecules by magnetically transferring the beads through processing
      solutions arrayed within small-diameter tubing. The process was automated by
      wrapping the tubing around a disc-like cassette and rotating it past a magnet
      using a programmable motor. This device recovered biomarkers at ~80% of the
      operator-dependent extraction method published previously. The device was
      validated by extracting biomarkers from a panel of surrogate patient samples
      containing clinically relevant concentrations of (1) influenza A RNA in nasal
      swabs, (2) Escherichia coli DNA in urine, (3) Mycobacterium tuberculosis DNA in
      sputum, and (4) Plasmodium falciparum protein and DNA in blood. The device
      successfully extracted each biomarker type from samples representing low levels
      of clinically relevant infectivity (i.e., 7.3 copies/uL of influenza A RNA, 405
      copies/uL of E. coli DNA, 0.22 copies/uL of TB DNA, 167 copies/uL of malaria
      parasite DNA, and 2.7 pM of malaria parasite protein).

PMID- 26194106
TI  - Noninvasive Arterial Testing in Patients With Diabetes: A Guide for Foot and
      Ankle Surgeons.
AB  - BACKGROUND: This study was designed to compare the findings of noninvasive
      arterial testing in patients with and without diabetic foot pathology. METHODS:
      The ABI (ankle brachial index), TBI (toe brachial index), and great toe pressures
      were measured in 207 patients. PAD (peripheral artery disease) was defined as an
      ABI < 0.91 on either extremity or a TBI < 0.7. RESULTS: PAD was identified in 103
      of the 207 patients (49.8%), 80 patients with diabetic foot pathology and 23
      patients with nondiabetic foot pathology. Although patients with diabetic foot
      pathology were 1.4 times more likely to have PAD compared to patients without
      diabetic pathology, this increased risk was not statistically significant (OR
      1.41 [95% CI 0.75-2.64], P = .28). Patients with PAD and diabetic foot pathology
      were 4.9 times more likely to have ischemia (toe pressure < 60 mm Hg) than
      patients with PAD and nondiabetic foot pathology (OR 4.93 [95% CI 1.35-17.94], P
      < .05). Patients on dialysis had a 7.3 times increased likelihood of having PAD
      compared to patients not on dialysis (OR 7.3 [95% CI 1.6-33.6], P < .01).
      Patients with absent pedal pulses were 4.9 more likely to have PAD than patients
      with normal pulses (OR 4.9 [95% CI 2.6-9.4], P < .0001). PAD was identified in 97
      of 188 patients (51.6%) with peripheral neuropathy compared to 6 of 19 patients
      (31.5%) without peripheral neuropathy (OR 2.31 [95% CI 0.84-6.33], P = .10).
      CONCLUSIONS: Combining the ABI with TBI improved the ability to diagnose PAD in
      diabetic patients because the ABI has high specificity (low false positives) and
      the TBI has high sensitivity (low false negatives). The TBI was more reliable in
      patients with noncompressible arteries, medial artery calcinosis and/or
      neuropathy. Due to the relative incompressibility of calcified distal arteries in
      patients with DM, the ABI may be within normal limits in patients with PAD. This
      false negative result may lead surgeons to assume that normal perfusion is
      present.

PMID- 26194104
TI  - Marsupials and monotremes possess a novel family of MHC class I genes that is
      lost from the eutherian lineage.
AB  - BACKGROUND: Major histocompatibility complex (MHC) class I genes are found in the
      genomes of all jawed vertebrates. The evolution of this gene family is closely
      tied to the evolution of the vertebrate genome. Family members are frequently
      found in four paralogous regions, which were formed in two rounds of genome
      duplication in the early vertebrates, but in some species class Is have been
      subject to additional duplication or translocation, creating additional clusters.
      The gene family is traditionally grouped into two subtypes: classical MHC class I
      genes that are usually MHC-linked, highly polymorphic, expressed in a broad range
      of tissues and present endogenously-derived peptides to cytotoxic T-cells; and
      non-classical MHC class I genes generally have lower polymorphism, may have
      tissue-specific expression and have evolved to perform immune-related or non
      immune functions. As immune genes can evolve rapidly and are subject to different
      selection pressure, we hypothesised that there may be divergent, as yet
      unannotated or uncharacterised class I genes. RESULTS: Application of a novel
      method of sensitive genome searching of available vertebrate genome sequences
      revealed a new, extensive sub-family of divergent MHC class I genes, denoted as
      UT, which has not previously been characterized. These class I genes are found in
      both American and Australian marsupials, and in monotremes, at an evolutionary
      chromosomal breakpoint, but are not present in non-mammalian genomes and have
      been lost from the eutherian lineage. We show that UT family members are
      expressed in the thymus of the gray short-tailed opossum and in other immune
      tissues of several Australian marsupials. Structural homology modelling shows
      that the proteins encoded by this family are predicted to have an open, though
      short, antigen-binding groove. CONCLUSIONS: We have identified a novel sub-family
      of putatively non-classical MHC class I genes that are specific to marsupials and
      monotremes. This family was present in the ancestral mammal and is found in
      extant marsupials and monotremes, but has been lost from the eutherian lineage.
      The function of this family is as yet unknown, however, their predicted structure
      may be consistent with presentation of antigens to T-cells.

PMID- 26194107
TI  - Efficient Direct Reduction of Graphene Oxide by Silicon Substrate.
AB  - Graphene has been studied for various applications due to its excellent
      properties. Graphene film fabrication from solutions of graphene oxide (GO) have
      attracted considerable attention because these procedures are suitable for mass
      production. GO, however, is an insulator, and therefore a reduction process is
      required to make the GO film conductive. These reduction procedures require
      chemical reducing agents or high temperature annealing. Herein, we report a novel
      direct and simple reduction procedure of GO by silicon, which is the most widely
      used material in the electronics industry. In this study, we also used silicon
      nanosheets (SiNSs) as reducing agents for GO. The reducing effect of silicon was
      confirmed by various characterization methods. Furthermore, the silicon wafer was
      also used as a reducing template to create a reduced GO (rGO) film on a silicon
      substrate. By this process, a pure rGO film can be formed without the impurities
      that normally come from chemical reducing agents. This is an easy and
      environmentally friendly method to prepare large scale graphene films on Si
      substrates. 

PMID- 26194108
TI  - Unveiling hidden ferrimagnetism and giant magnetoelectricity in polar magnet
      Fe2Mo3O8.
AB  - Magnetoelectric (ME) effect is recognized for its utility for low-power
      electronic devices. Largest ME coefficients are often associated with phase
      transitions in which ferroelectricity is induced by magnetic order.
      Unfortunately, in these systems, large ME response is revealed only upon
      elaborate poling procedures. These procedures may become unnecessary in single
      polar-domain crystals of polar magnets. Here we report giant ME effects in a
      polar magnet Fe2Mo3O8 at temperatures as high as 60 K. Polarization jumps of 0.3
      MUC/cm(2), and repeated mutual control of ferroelectric and magnetic moments with
      differential ME coefficients on the order of 10(4) ps/m are achieved.
      Importantly, no electric or magnetic poling is needed, as necessary for
      applications. The sign of the ME coefficients can be switched by changing the
      applied "bias" magnetic field. The observed effects are associated with a hidden
      ferrimagnetic order unveiled by application of a magnetic field.

PMID- 26194109
TI  - Molecular mechanisms of xylose utilization by Pseudomonas fluorescens:
      overlapping genetic responses to xylose, xylulose, ribose and mannitol.
AB  - Bacterial degradation of xylose is sequentially mediated by two enzymes - an
      isomerase (XutA) and a xylulokinase (XutB) - with xylulose as an intermediate.
      Pseudomonas fluorescens SBW25, though capable of growth on xylose as a sole
      carbon source, encodes only one degradative enzyme XutA at the xylose utilization
      (xut) locus. Here, using site-directed mutagenesis and transcriptional assays, we
      have identified two functional xylulokinase-encoding genes (xutB1 and xutB2) and
      further show that expression of xutB1 is specifically induced by xylose.
      Surprisingly, xylose-induced xutB1 expression is mediated by the mannitol
      responsive regulator MtlR, using xylulose rather than xylose as the direct
      inducer. In contrast, expression of the xutA operon is regulated by XutR - a
      transcriptional activator of the AraC family - in a xylose-, xylulose- and ribose
      dependent manner. Detailed genetic and biochemical analyses of XutR, including
      DNase I footprinting assays, suggest an unconventional model of XutR regulation
      that does not involve DNA-looping, a mechanism typically found for AraC-type
      regulators from enteric bacteria. XutR functions as a dimer and recognizes two
      inverted repeat sequences, but binding to one half site is weak thus requiring an
      inducer molecule such as xylose for activation. 

PMID- 26194110
TI  - Comparison of microperc and mini-percutaneous nephrolithotomy for medium-sized
      lower calyx stones.
AB  - The objective of this study was to present the outcomes of comparative clinical
      study of microperc versus mini-percutaneous nephrolithotomy (mini-PNL) in the
      treatment of lower calyx stones of 10-20 mm. Patients with lower calyx stones
      treated with microperc (Group-1) or mini-PNL (Group-2) between 2011 and 2014 were
      retrospectively analyzed. Demographics of the patients were compared, including
      age, gender, BMI, stone size, laterality and procedural parameters (operation and
      fluoroscopy time), and outcomes (success and complication rates). A total of 98
      patients were evaluated, assigned to Group-1 (n = 58) and to Group-2 (n = 40).
      Groups were statistically similar in terms of age, stone size, and BMI (p = 0.3,
      0.07, 0.6, respectively). The mean procedure and fluoroscopy duration for Group-1
      were 43.02 +/- 27.98 min and 112.05 +/- 72.5 s, and 52.25 +/- 23.09 min and
      138.53 +/- 56.39 s in Group-2 (p = 0.006 and 0.006). The mean hematocrit drop was
      significantly higher in Group-2 compared to Group-1 (3.98 vs. 1.96%; p < 0.001);
      however, none of the cases required blood transfusion. Overall complication rates
      exhibited no statistically significant difference (p = 0.57). Stone-free status
      was similar (86.2 vs. 82.5%, p = 0.66). The tubeless procedure rate was
      significantly higher in Group-1 (p < 0.001). In Group-2, duration of
      hospitalization was significantly longer than in Group-1 (2.63 vs. 1.55 days; p <
      0.01). Outcomes of the present retrospective study show that microperc is a
      treatment option for medium-sized lower calyx stone, being associated with lower
      blood loss, procedure, reduced fluoroscopy and hospitalization time, and a higher
      tubeless rate.

PMID- 26194112
TI  - Investigation of genes important in neurodevelopment disorders in adult human
      brain.
AB  - Several neurodevelopmental disorders (NDDs) are caused by mutations in genes
      expressed in fetal brain, but little is known about these same genes in adult
      human brain. Here, we test the hypothesis that genes associated with NDDs
      continue to have a role in adult human brain to explore the idea that NDD
      symptoms may be partially a result of their adult function rather than just their
      neurodevelopmental function. To demonstrate adult brain function, we performed
      expression analyses and ChIPseq in human neural stem cell(NSC) lines at different
      developmental stages and adult human brain, targeting two genes associated with
      NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been
      associated with NDDs. Analysis of DNA interaction sites in neural stem cells
      reveals high (40-50 %) overlap between proliferating and differentiating cells
      for each gene in temporal space. Studies in adult brain demonstrate that
      consensus sites are similar to NSCs but occur at different genomic locations. We
      also performed expression analyses using BrainSpan data for NDD-associated genes
      SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A,
      and DYRK1A and find high expression of these genes in adult brain, at least
      comparable to developing human brain, confirming that genes associated with NDDs
      likely have a role in adult tissue. Adult function of genes associated with NDDs
      might be important in clinical disease presentation and may be suitable targets
      for therapeutic intervention.

PMID- 26194113
TI  - Introduction of a Psychosocial Post-Discharge Intervention Program Aimed at
      Reducing Psychiatric Rehospitalization Rates and at Improving Mental Health and
      Functioning.
AB  - PURPOSE: Based on the premises of assertive community treatment and intensive
      case management, we designed a program delivered by social workers that is
      targeted at transition to community treatments and social support. DESIGN AND
      METHODS: Narrative review and qualitative analysis of three patients who
      participated in the program. FINDINGS: Case reports revealed that patients'
      social networks are small and their relationships are commonly conflictual and
      unstable. PRACTICE IMPLICATIONS: Access to patients' social networks is a
      challenging task. Based on our preliminary experiences with the program, we
      suggest that more efforts should be made to enhance patients' social and
      interpersonal abilities.

PMID- 26194111
TI  - The role of 15-LOX-1 in colitis and colitis-associated colorectal cancer.
AB  - INTRODUCTION: Chronic inflammation is known to be mechanistically linked to the
      development of cancer. This article reviews and discusses the role of 15
      lipoxygenase-1 (15-LOX-1) in the resolution of colitis and prevention of colitis
      associated colorectal cancer. DISCUSSION: 15-LOX-1 is an inducible and highly
      regulated enzyme in cells that play an important role in the production of lipid
      signaling mediators from linoleic acid and arachidonic acid. Together, these
      acids and 15-LOX-1 are the driving force for the resolution of acute and chronic
      inflammation in normal cells. Widespread inflammation can progress from local
      inflammation to ulcerative colitis, tumorigenesis, and finally invasive,
      metastatic, or benign colon cancer. Thus, reversing inflammation will halt the
      proliferation of cancerous cells. Decreased expression of 15-LOX-1 may lead to
      the development of colitis-associated colorectal cancer and colorectal cancer.
      CONCLUSION: n-3 Polyunsaturated fatty acids are potent anti-inflammatory and pro
      resolution products of 15-LOX-1 that can potentially prevent colitis-associated
      colorectal cancer and colorectal cancer.

PMID- 26194114
TI  - No Association of Chronic Cerebrospinal Venous Insufficiency with Multiple
      Sclerosis.

PMID- 26194115
TI  - Translation, cultural adaptation, and validation of the Sleep Apnea Quality of
      Life Index (SAQLI) in Persian-speaking patients with obstructive sleep apnea.
AB  - PURPOSE: The aim of this study was the translation, cross-cultural adaptation,
      and validation of the Sleep Apnea Quality of Life Index (SAQLI) in Persian
      speaking patients with obstructive sleep apnea (OSA). METHODS: Ninety-six
      patients with OSA completed a series of questionnaires including SAQLI, Epworth
      Sleepiness Scale (ESS),10-item Functional Outcomes of Sleep Questionnaire (FOSQ
      10), and Medical Outcome Survey Short form 12 (SF-12) for assessment of
      reliability, validity, and responsiveness of Persian version of SAQLI. RESULTS:
      The Persian version of SAQLI had a very good internal consistency and also
      demonstrated good test-retest reliability. Concurrent validity was confirmed by
      significant correlations with ESS, FOSQ-10 and SF-12 subscale scores. Comparison
      of SAQLI scores in groups of patients categorized by ESS showed the high
      discriminative power of this instrument. However, there was no significant
      difference in the SAQLI scores of patients with mild, moderate, and severe sleep
      apnea. The results of sensitivity to change verified that the SAQLI was able to
      detect changes after continuous positive airway pressure (CPAP) treatment.
      CONCLUSION: The findings of this study indicate that the Persian version of SAQLI
      is a reliable, valid, and responsive measure for evaluation of quality of life in
      patients with OSA.

PMID- 26194116
TI  - Bacillus stamsii sp. nov., a facultatively anaerobic sugar degrader that is
      numerically dominant in freshwater lake sediment.
AB  - A novel type of anaerobic bacteria was previously isolated from profundal lake
      sediment by direct dilution of the sediment in mineral agar medium containing
      glucose and a background lawn of Methanospirillum hungatei as a syntrophic
      partner. The isolated bacteria grouped with aerobic Bacillus spp. according to
      their 16S rRNA gene sequence, and the most closely related species is Bacillus
      thioparans. Fermentative growth of the novel strain with glucose was possible
      only in the presence of syntrophic partners, and cocultures produced acetate and
      methane, in some cases also lactate and traces of succinate as fermentation
      products. In contrast, the closely related strains Bacillus jeotgali and Bacillus
      sp. strain PeC11 are able to grow with glucose axenically by mixed acid
      fermentation yielding lactate, acetate, formate, succinate, and ethanol as
      fermentation products. Alternatively, the isolated strain grew anaerobically in
      pure culture if pyruvate was added to glucose-containing media, and lactate,
      acetate and formate were the major fermentation products, but the strain never
      produced ethanol. Aerobic growth was found with a variety of organic substrates
      in the presence of partly reduced sulfur compounds. In the absence of sulfide and
      oxygen, nitrate served as an electron acceptor. Strain BoGlc83 was characterized
      as the type strain of a new species for which the name Bacillus stamsii sp. nov.
      (DSM 19598=JCM 30025) is proposed. 

PMID- 26194117
TI  - Anatomical study of the articular branch of the lateral pectoral nerve to the
      shoulder joint.
AB  - PURPOSE: The purpose of this study was to document the distribution of the
      articular branch of the lateral pectoral nerve (LPN) to the shoulder and to
      identify a suitable point for its blockade. METHODS: This study involved the
      dissection of 43 shoulders of 22 unembalmed cadavers (6 male and 16 female) to
      identify the LPN and its articular branch to the shoulder. To identify the
      suitable anatomical point for blocking the articular branch of the LPN, several
      anatomical landmarks around the shoulder were measured. RESULTS: The articular
      branch of the LPN to the shoulder was present in 29 of 43 cases (67.4 %). The
      appropriate point to block the articular branch of the LPN was identified at a
      mean distance of 1.5 cm below the clavicle, on the line connecting the closest
      points between the clavicle and the coracoid process, and at a mean depth of 1.0
      cm from the skin. CONCLUSION: The articular branch of the LPN to the shoulder, as
      well as the muscular and cutaneous branches of the LPN, covers a portion of the
      shoulder joint with suprascapular and axillary nerves. Surgeons might consider a
      peripheral block of the suprascapular, axillary, and LPNs to provide maximum
      block coverage after shoulder joint surgery.

PMID- 26194118
TI  - Posterior reference guides do not always maintain the size of posterior femoral
      condyles in TKA.
AB  - PURPOSE: Posterior reference guides are provided by many manufacturers. However,
      the true posterior femoral condyle bone resection thicknesses using posterior
      reference guides are not stated by the manufacturers. The purpose of this study
      was to analyse the influence of the posterior reference guide designs on the
      posterior femoral condyle bone resection thickness. METHODS: Thickness of
      posterior femoral condyle bone resection and thickness of prostheses were
      investigated in 8 types of total knee prostheses using the production drawings
      provided by the manufacturers. RESULTS: Posterior femoral condyle bone resection
      thickness differed between prostheses. Change in size of the medial posterior
      condyle ranged from -0.5 to 1.4 mm at 0 degrees  external rotation, from -2.9 to
      1.4 mm at 3 degrees  external rotation, and from -5.3 to 1.4 mm at 6 degrees 
      external rotation. Change in size of lateral posterior condyle ranged from -0.5
      to 1.4 mm at 0 degrees  external rotation, from -0.4 to 3.4 mm at 3 degrees 
      external rotation, and from -0.4 to 5.3 mm at 6 degrees  external rotation.
      CONCLUSIONS: This study showed that posterior femoral condyle bone resection
      thickness was different for each posterior reference guide. The rotation centre
      of posterior reference guides influenced the bone resection thickness in the
      posterior femoral condyle. The size of the posterior femoral condyles increased
      in some guides but decreased in other guides. The maximum differences in size
      changes of the posterior femoral condyles between the guides were 1.9 mm at 0
      degrees  external rotation, 4.1 mm at 3 degrees  external rotation, and 6.3 mm at
      6 degrees  external rotation. To control the size of posterior femoral condyles,
      the posterior reference guide design should be checked before use.

PMID- 26194119
TI  - Local adaptation: Mechanical fit between floral ecotypes of Nerine humilis
      (Amaryllidaceae) and pollinator communities.
AB  - Geographic variation in floral morphology is often assumed to reflect geographic
      variation in pollinator communities and associated divergence in selective
      pressures. We studied populations of Nerine humilis (Amaryllidaceae) to assess
      whether geographic variation in floral form is the result of local adaptation to
      different pollinator communities. We first tested for associations between floral
      traits and visitor communities, and found that populations with similar floral
      morphologies were visited by similar insect communities. Mean style length in
      each population was also closely associated with the mean body length of the
      local visitor community. A reciprocal translocation experiment demonstrated that
      native phenotypes set more seed than translocated phenotypes. Single visitation
      experiments showed that native flowers received more pollen, and set more seed
      per visit, than introduced phenotypes in both populations. This suggests that the
      effectiveness of pollinator visits is determined by the degree of mechanical fit
      between flowers and visitors. We provide strong evidence that the observed among
      population variation in floral traits is an adaptive response to geographic
      variation in the pollinator community. 

PMID- 26194120
TI  - Pharmacological basis and scientific rationale underlying the targeted use of
      inhaled corticosteroid/long-acting beta2-adrenergic agonist combinations in
      chronic obstructive pulmonary disease treatment.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a complex
      respiratory disorder, whose medical and socioeconomic burden as one of the main
      causes of morbidity and mortality is increasing worldwide. COPD pathophysiology
      includes chronic airway/lung inflammation and progressive airflow limitation.
      Therefore, anti-inflammatory and bronchodilator agents are key players in COPD
      treatment. AREAS COVERED: This review article discusses the complementary
      molecular interactions connecting the respective mechanisms of action of inhaled
      corticosteroids (ICS) and long-acting beta2-adrenergic agonists (LABAs).
      Moreover, attention is also focused on clinical trials, which have shown that
      ICS/LABA combinations are very effective in improving COPD symptoms and lung
      function, being also able to significantly reduce disease exacerbations. EXPERT
      OPINION: In selected subgroups of COPD patients, ICS/LABA combinations represent
      a very useful therapeutic approach for this widespread chronic respiratory
      disease. In addition to the well-known fixed-dose drug associations such as
      fluticasone propionate/salmeterol xinafoate and budesonide/formoterol fumarate,
      other newly developed ICS/LABA combinations are currently emerging as very
      interesting pharmacological options for COPD treatment.

PMID- 26194121
TI  - Family history of venous thromboembolism and risk of hospitalized thromboembolism
      in cancer patients: A nationwide family study.
AB  - BACKGROUND: The importance of family history of venous thromboembolism (VTE) in
      cancer patients is unclear. We conducted a nationwide study to determine whether
      family history of VTE is a risk factor for hospitalized VTE in cancer patients.
      METHODS: The Swedish Multi-Generation Register was linked to the Swedish Hospital
      Discharge Register and the Swedish Cancer Registry. Familial (sibling/parent
      history of VTE) hazard ratios (HRs) for VTE in 20 cancer types were determined by
      cause-specific Cox regression for 258877 cancer patients in 1987-2010 without
      previous VTE. Familial HRs were also determined in 7644203 individuals without
      cancer or VTE before 1987, with follow-up in 1987-2010. RESULTS: Significant
      familial HRs for VTE in cancer patients were observed for the following cancer
      types: cancers of the breast (HR=1.79), lung (HR=1.21), colon (HR=1.30), prostate
      (HR=1.46), testis (HR=2.02), nervous system (HR=1.31), stomach (HR=1.73), and
      rectum (HR=1.77), as well as melanoma (HR=1.71), non-Hodgkin lymphoma (HR=1.32),
      myeloma (HR=1.69), and leukemia (HR=1.44). In a time-dependent analysis the
      familial HRs for VTE were significant before diagnosis of cancer (p-values
      <0.0001). After diagnosis of cancer the familial HRs VTE were weaker, with
      significant HRs for 12 cancer types. On an additive scale, the joint effect of
      cancer and family history was significantly increased compared to separate
      effects in four cancer types. However, for certain cancers the familial VTE cases
      were limited. CONCLUSIONS: Family history of VTE is a risk factor for VTE in
      several cancer types. However, familial factors are relatively more important in
      non-cancer than in cancer patients.

PMID- 26194122
TI  - A case of perioperative glucose control by using an artificial pancreas in a
      patient with glycogen storage disease.
AB  - A 57-year-old woman was diagnosed with type I glycogen storage disease in her
      twenties. She had undergone hepatectomy under general anesthesia with epidural
      anesthesia. Fifty minutes after the induction of anesthesia, a 20-gauge venous
      catheter was inserted in the patient's right hand, and an artificial pancreas
      (STG-55, Nikkiso Co., Tokyo, Japan) was connected for continuous glucose
      monitoring and automatic glucose control. Insulin was infused when the blood
      glucose level reached 120 mg/dL or higher, and glucose was infused when the level
      fell to 100 mg/dL or lower. After the Pringle maneuver, the blood glucose level
      increased, and insulin was administered automatically via an artificial pancreas.
      Hypoglycemia did not occur during the operation. After total parenteral nutrition
      was started in the intensive care unit (ICU), the blood glucose level increased,
      and the artificial pancreas controlled the blood glucose level through automatic
      insulin administration. Thirty-four hours after admission to the ICU, the
      artificial pancreas was removed because the blood sampling failed. After the
      removal of the artificial pancreas, blood glucose level was measured every 2 h
      until extubation. During the ICU stay, hypoglycemia never occurred, with the
      average blood glucose level being 144 mg/dL. In conclusion, the use of an
      artificial pancreas for perioperative blood glucose management in a patient with
      glycogen storage disease had the beneficial effect of enabling the management of
      blood glucose levels without hypoglycemia. 

PMID- 26194123
TI  - [New Therapeutic Agent for Chronic Hepatitis C: Direct Acting Agent].
AB  - Peg-interferon and ribavirin has been the standard therapy of chronic hepatitis C
      for the past 15 years in Korea. However, the treatment paradigm is changing.
      Direct acting agents (DAAs) are oral pills that can be easily taken. In addition,
      DAAs are more effective and have less adverse reactions compared to the
      previously used drugs. Chronic hepatitis C is hard to treat because the virus is
      error-prone virus. Host immunity is helpless against the hepatitis C virus since
      it evades the host immunity through various complex mechanisms. There are 6
      genotypes. Quasispecies can co-exist even in the same patients. The treatment
      strategy is based on the combination of the individual drug corresponding to each
      step of viral replication process. NS5B nucleosides are the most powerful and
      effective drug available until now. Other drugs with different mechanisms of
      action can be used to provide synergy. NS5A and NS5B inhibition drugs currently
      belong to the leading group amongst many DAAs. These drugs will soon be available
      in Korea. We have to know the merits and adverse drug reactions of the new drug. 

PMID- 26194124
TI  - [Efficacy and Safety of FOLFIRI after Failure of FOLFOX-4 in Advanced Gastric
      Cancer].
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate the efficacy and
      safety of irinotecan based FOLFIRI chemotherapy as a second-line treatment after
      failure of FOLFOX-4 chemotherapy in patients with advanced gastric cancer.
      METHODS: Fifty-two patients who were pathologically diagnosed with unresectable
      gastric cancer and received FOLFIRI chemotherapy after failure of FOLFOX-4
      chemotherapy between September 2005 and February 2012 were enrolled in this
      study. Data were collected by retrospectively reviewing the medical records. The
      response to chemotherapy was assessed every 3 cycles by World Health Organization
      criteria and long term survival was analyzed. The toxicities were evaluated for
      every course of chemotherapy according to National Cancer Institution (NCI)
      toxicity criteria version 3.0. RESULTS: Median age of the patients was 57 years.
      Median overall survival (OS) and time to progression (TTP) were 7.8 and 5 months,
      respectively. The number of patients showing complete remission, partial
      remission, stable disease, and progressive disease were 0 (0.0%), 9 (17.3%), 30
      (57.7%), and 13 (25.0%), respectively. The overall response rate was 17.3%.
      During a total of 345 cycles, anemia worse than NCI toxicity grade 3 occurred in
      2.9%, leukopenia in 20.3%, neutropenia in 12.2%, and thrombocytopenia in 1.5%.
      Patients with less organ involvement by metastasis, less than 34 U/mL of CA 19-9
      and good responsiveness to third cycle of second line chemotherapy were
      associated with longer OS and TTP. CONCLUSIONS: FOLFIRI chemotherapy has a modest
      efficacy with acceptable toxicities in patients with advanced gastric cancer as a
      second-line treatment. Further well-controlled studies are needed to elucidate
      the efficacy of FOLFIRI chemotherapy as second-line treatment in patients with
      advanced stomach cancer.

PMID- 26194125
TI  - [Efficacy and Safety of New Prokinetic Agent Benachio Q Solution(r) in Patients
      with Postprandial Distress Syndrome Subtype in Functional Dyspepsia: A Single
      center, Randomized, Double-blind, Placebo-controlled Pilot Study].
AB  - BACKGROUND/AIMS: Functional dyspepsia (FD) is a gastrointestinal disorder in
      which the patient suffers from chronic abdominal symptoms despite the absence of
      organic disease. Benachio Q solution (soln.)(r) is a new prokinetic herbal
      medicine. The aim of the present study is to determine the efficacy and safety of
      Benachio Q soln.(r) in patients with postprandial distress syndrome (PDS) subtype
      in FD. METHODS: A single-center, randomized, double-blind, placebo-controlled
      pilot study was performed in 20 patients with PDS. Patients were assigned to
      receive either Benachio Q soln.(r) or placebo three times a day. After 4 weeks of
      treatment, the data on response rates, symptoms severity of PDS and gastric
      emptying time were analyzed to evaluate its efficacy. Adverse events, laboratory
      tests and vital sign were analyzed to assess its safety. RESULTS: Nine patients
      were assigned to Benachio group and 10 patients to placebo group. The response
      rate after 4 weeks was 44.4% and 20.0% in Benachio and placebo group,
      respectively (p=0.350). The response rate during the first week in Benachio group
      was better compared to that of placebo group with marginal difference (33.3% vs.
      0.0%, p=0.087). Changes of severity score in early satiety on second and third
      week were -1.8 +/- 0.6, -1.9 +/- 0.4 and -1.3 +/- 0.5, -1.4 +/- 0.6 in Benachio
      and placebo group, respectively (p=0.059 vs. p=0.033). No adverse event was
      observed. CONCLUSIONS: The new herbal drug, Benachio Q soln.(r) seems to improve
      the symptoms of PDS subtype in FD and could be used safely. Further larger trial
      is needed in the future.

PMID- 26194126
TI  - Clinical Characteristics and Outcomes of Pyogenic Liver Abscess in Elderly Korean
      Patients.
AB  - BACKGROUND/AIMS: Incidence of pyogenic liver abscess (PLA) has been increasing
      worldwide, especially in the elderly population. Therefore, the aim of this study
      is to elucidate the clinical features and outcomes of PLA in elderly patients.
      METHODS: A total of 602 patients diagnosed with PLA from January 2003 to January
      2013 were analyzed retrospectively. The patients were divided according to two
      age groups;>= 65 years (n=296) and <65 years (n=306). RESULTS: The mean age was
      73.59 +/- 5.98 (range, 65-93) years in the elderly group. Significantly higher
      incidence of females (52.4% vs. 29.1%, p<0.001), hepatobiliary disease (41.2% vs.
      24.8%, p<0.001), hepatobiliary procedure (29.4% vs. 13.7%, p<0.001), underlying
      malignancy (18.2% vs. 4.6%, p<0.001), culture positivity of resistant organism
      (20.6% vs. 14.4%, p=0.047), occurrence of complication (19.6% vs. 12.8%,
      p=0.026), and higher white blood cell (13.44 +/- 6.56 vs. 12.26 +/- 5.89,
      p=0.021), but lower rates of right lobe abscess (67.2% vs. 80.4%, p<0.001), fever
      (68.6% vs. 79.3%, p=0.003), and lower CRP (16.79 +/- 9.67 vs. 18.80 +/- 9.86,
      p=0.012) was observed in elderly PLA patients, compared to younger patients.
      Regarding complications, elderly patients had higher incidence of septic shock
      (8.1% vs. 2.3%, p=0.001) and cardiovascular disease (2% vs. 0%, p=0.014).
      CONCLUSIONS: More atypical presentations and complications tend to occur in
      elderly PLA patients compared with younger patients. Clinicians should be aware
      of these age-related differences in PLA and devise management strategies
      accordingly.

PMID- 26194127
TI  - Clinical Significance of Biliary Dilatation and Cholelithiasis after Subtotal
      Gastrectomy.
AB  - BACKGROUND/AIMS: The well-organized study to support that increased
      cholelithiasis and bile duct dilatation can occur after gastrectomy has not been
      reported. The aim of this study was to determine the incidence of cholelithiasis
      and the degree of common bile duct (CBD) dilatation in patients undergoing
      subtotal gastrectomy, compared to those undergoing endoscopic treatment for
      gastric cancer. METHODS: Patients who diagnosed with gastric cancer and received
      treatment at six academic referral centers were investigated for the incidence
      and time of cholelithiasis and the degree of CBD dilatation after treatment by
      analysis of 5-year follow-up CTs. The operation group underwent subtotal
      gastrectomy without vagotomy, while in the control group endoscopic treatment was
      administered for gastric cancer. RESULTS: A total of 802 patients were enrolled
      in 5-year analysis (735 patients in the operation group and 67 patients in the
      control group). Cholelithiasis occurred in 47 patients (6.39%) in the operation
      group and 3 patients (4.48%) in the control group (p=0.7909). The incidences of
      cholelithiasis were 4.28% in Billoth-I and 7.89% in Billoth-II (p=0.0487). The
      diameter of proximal CBD and distal CBD increased by 1.11 mm and 1.41 mm,
      respectively, in the operation group, compared to 0.4 mm and 0.38 mm,
      respectively, in the control group (p?0.05). Patients with increased CBD
      dilatation more than 5 mm showed statistically significant increases in alkaline
      phosphatase and gamma-glutamyltransferase. CONCLUSIONS: The incidence of
      cholelithiasis was not increased due to subtotal gastrectomy without vagotomy,
      but the incidence was higher after Billoth-II compared to Billoth-I. In addition,
      significant change in the CBD diameter was observed after subtotal gastrectomy.

PMID- 26194128
TI  - [A Case of Intra-abdominal Paragonimiasis Mimicking Metastasis of Lung Cancer
      Diagnosed by Endoscopic Ultrasound-guided Fine Needle Aspiration].
AB  - Paragonimiasis has been continuously decreasing in Korea. However, it still
      occurs by ingesting raw or incompletely cooked fresh water crab or crayfish. The
      diagnosis of paragonimiasis is challenging because of its rarity. It may be
      confused with other inflammatory disease or carcinomatosis. Endoscopic ultrasound
      guided fine needle aspiration (EUS-FNA) has lower risk of complications such as
      bleeding, perforation than percutaneous fine needle aspiration. EUS-FNA is more
      accurate and popular method to find mucosal or submucosal tumors and the lesions
      of several organs. Benign and malignant tumors, infectious diseases have been
      diagnosed by EUS-FNA, but there was no report describing the use of EUS-FNA for
      diagnosing paragonimiasis. Herein, we present a 47-year-old male patient with
      paragonimiasis diagnosed by EUS-FNA. Imaging studies revealed mass lesions in the
      lung and peritoneal cavity, which was eventually confirmed as paragonimiasis
      using EUS-FNA. 

PMID- 26194129
TI  - [Successful Removal of Hard Sigmoid Fecaloma Using Endoscopic Cola Injection].
AB  - Colorectal fecaloma is hardening of feces into lumps of varying size that is much
      harder in consistency than a fecal impaction. Complications of colorectal
      fecaloma include ulceration, bleeding, perforation and obstruction of the colon.
      Most fecalomas are successfully removed by conservative treatment with laxatives,
      enemas and rectal evacuation to relieve fecal impaction. When conservative
      treatments have failed, a surgical intervention may be needed. Herein, we report
      a case of 4.7 cm sized sigmoid fecaloma showing no response to conservative
      treatments that was successfully removed by endoscopic fragmentation with Coca
      Cola injection instead of surgery. 

PMID- 26194130
TI  - Hepatocellular Carcinoma with Cervical Spine and Pelvic Bone Metastases
      Presenting as Unknown Primary Neoplasm.
AB  - The occurrence of hepatocellular carcinoma (HCC) is closely associated with viral
      hepatitis or alcoholic hepatitis. Although active surveillance is ongoing in
      Korea, advanced or metastatic HCC is found at initial presentation in many
      patients. Metastatic HCC presents with a hypervascular intrahepatic tumor and
      extrahepatic lesions such as lung or lymph node metastases. Cases of HCC
      presenting as carcinoma of unknown primary have been rarely reported. The authors
      experienced a case of metastatic HCC in a patient who presented with a metastatic
      bone lesion but no primary intrahepatic tumor. This case suggests that HCC should
      be considered as a differential diagnosis when evaluating the primary origin of
      metastatic carcinoma. 

PMID- 26194131
TI  - Volume-reserving Surgery after Photodynamic Therapy for Biliary Papillomatosis: A
      Case Report.
AB  - Biliary papillomatosis is rare, and its pathogenic mechanisms are not yet clear.
      Because of its high risk for malignancy transformation, surgical resection is
      regarded as a standard treatment. Photodynamic therapy (PDT) has been used by the
      intravenous administration of hematoporphyrin derivative followed by laser
      exposure. A photochemical process causes disturbance of the microvascular
      structure and degradation of membrane. Cholangitis is a major complication after
      PDT. A healthy 56-year-old man was diagnosed with biliary papillomatosis
      involving the common hepatic duct, both proximal intrahepatic bile ducts (IHD),
      and the right posterior IHD. After biliary decompression by endoscopic
      nasobiliary drainage, PDT was performed to avoid extensive liver resection and
      recurrence using endoscopic retrograde cholangiographic guidance. After portal
      vein embolization, the patient underwent extended right hemihepatectomy.
      Following administration of chemoradiation therapy with tegafur-uracil and 45 Gy
      due to local recurrence at postoperative 13 months, there was no local recurrence
      or distant metastases. This is the first case report on PDT for biliary
      papillomatosis in Korea. Preoperative PDT is beneficial for reducing the lesion
      in diffuse or multifocal biliary papillomatosis and may lead to curative and
      volume reserving surgery. Thus, PDT could improve the quality of life and prolong
      life expectation for biliary papillomatosis patients. 

PMID- 26194132
TI  - Association between age at menarche and diabetes in Korean post-menopausal women:
      results from the Korea National Health and Nutrition Examination Survey (2007
      2009).
AB  - Early menarche is known to be associated with diabetes, however this association
      remains controversial. Our study aimed to investigate the possible association
      between age at menarche and diabetes prevalence in post-menopausal Korean women.
      This study included 3,254 post-menopausal Korean women aged 50-85 years from the
      Korea National Health and Nutrition Examination Survey IV (KNHANES 2007-2009).
      Logistic regression analyses were used to estimate odds ratios (ORs) for diabetes
      prevalence. Levels of biochemical markers were compared according to groups by
      age at menarche. Women in the earlier menarche age group (10-12 years) showed
      higher levels of fasting blood glucose (FBG) and scores of homeostatic model
      assessment in the insulin resistance (HOMA-IR) index than other groups (p <0.05).
      After adjusting for potential confounding factors, early age at menarche was
      significantly associated with a higher prevalence of diabetes (OR 1.86, 95%
      confidence intervals [CI] 1.07-3.23). The observed association remained
      significant despite additional adjustment for body mass index and waist
      circumference (OR 1.82, 95% CI 1.03-3.23) and despite further adjustments for FBG
      levels and HOMA-IR index (OR 2.25, 95% CI 1.11-4.55). Our findings strengthen the
      hypothesis that younger age at menarche is associated with increased diabetes
      prevalence in the Korean population. 

PMID- 26194133
TI  - Is the human mirror neuron system plastic? Evidence from a transcranial magnetic
      stimulation study.
AB  - Virtual lesions in the mirror neuron network using inhibitory low-frequency (1Hz)
      transcranial magnetic stimulation (TMS) have been employed to understand its
      spatio-functional properties. However, no studies have examined the influence of
      neuro-enhancement by using excitatory high-frequency (20Hz) repetitive
      transcranial magnetic stimulation (HF-rTMS) on these networks. We used three
      forms of TMS stimulation (HF-rTMS, single and paired pulse) to investigate
      whether the mirror neuron system facilitates the motor system during goal
      directed action observation relative to inanimate motion (motor resonance), a
      marker of putative mirror neuron activity. 31 healthy individuals were randomized
      to receive single-sessions of true or sham HF-rTMS delivered to the left inferior
      frontal gyrus - a component of the human mirror system. Motor resonance was
      assessed before and after HF-rTMS using three TMS cortical reactivity paradigms:
      (a) 120% of resting motor threshold (RMT), (b) stimulus intensity set to evoke
      motor evoked potential of 1-millivolt amplitude (SI1mV) and (c) a short latency
      paired pulse paradigm. Two-way RMANOVA showed a significant group (true versus
      sham) X occasion (pre- and post-HF-rTMS motor resonance) interaction effect for
      SI1mV [F(df)=6.26 (1, 29), p=0.018] and 120% RMT stimuli [F(df)=7.01 (1, 29),
      p=0.013] indicating greater enhancement of motor resonance in the true HF-rTMS
      group than the sham-group. This suggests that HF-rTMS could adaptively modulate
      properties of the mirror neuron system. This neuro-enhancement effect is a
      preliminary step that can open translational avenues for novel brain stimulation
      therapeutics targeting social-cognition deficits in schizophrenia and autism. 

PMID- 26194134
TI  - Metazoan tRNA introns generate stable circular RNAs in vivo.
AB  - We report the discovery of a class of abundant circular noncoding RNAs that are
      produced during metazoan tRNA splicing. These transcripts, termed tRNA intronic
      circular (tric)RNAs, are conserved features of animal transcriptomes. Biogenesis
      of tricRNAs requires anciently conserved tRNA sequence motifs and processing
      enzymes, and their expression is regulated in an age-dependent and tissue
      specific manner. Furthermore, we exploited this biogenesis pathway to develop an
      in vivo expression system for generating "designer" circular RNAs in human cells.
      Reporter constructs expressing RNA aptamers such as Spinach and Broccoli can be
      used to follow the transcription and subcellular localization of tricRNAs in
      living cells. Owing to the superior stability of circular vs. linear RNA
      isoforms, this expression system has a wide range of potential applications, from
      basic research to pharmaceutical science. 

PMID- 26194135
TI  - Nonorthogonal tRNA(cys)(Amber) for protein and nascent chain labeling.
AB  - In vitro-transcribed suppressor tRNAs are commonly used in site-specific
      fluorescence labeling for protein and ribosome-bound nascent chains (RNCs)
      studies. Here, we describe the production of nonorthogonal Bacillus subtilis
      tRNA(cys)(Amber) from Escherichia coli, a process that is superior to in vitro
      transcription in terms of yield, ease of manipulation, and tRNA stability. As
      cysteinyl-tRNA synthetase was previously shown to aminoacylate tRNA(cys)(Amber)
      with lower efficiency, multiple tRNA synthetase mutants were designed to optimize
      aminoacylation. Aminoacylated tRNA was conjugated to a fluorophore to produce
      BODIPY FL-cysteinyl-tRNA(cys)(Amber), which was used to generate ribosome-bound
      nascent chains of different lengths with the fluorophore incorporated at various
      predetermined sites. This tRNA tool may be beneficial in the site-specific
      labeling of full-length proteins as well as RNCs for biophysical and biological
      research.

PMID- 26194136
TI  - An exploration of physical activity and wellbeing in university employees.
AB  - AIMS: The aim was to explore levels of physical activity (PA) and mental
      wellbeing in university employees, as well as barriers to and incentives for
      workplace PA. METHODS: An electronic survey was distributed to all staff at one
      UK university. The survey consisted of a PA stages of change questionnaire, an
      international PA questionnaire (short-form), the Warwick-Edinburgh Mental Well
      being Scale (WEMWBS), questions on perceived barriers to and incentives for
      workplace PA, questions on methods of enhancing employee wellbeing and
      demographics. A self-selected sample participated in two focus groups to explore
      key themes arising from the survey. Descriptive statistics were reported for
      survey data; associations between PA and wellbeing were tested for using Kruskal
      Wallis with post hoc Mann-Whitney. Descriptive, thematic analysis was performed
      on focus group transcripts. RESULTS: A total of 502 surveys were completed (34%
      response rate); 13 staff participated in focus groups. In all, 42% of the sample
      reported PA below the recommended guideline amount. Females were less active than
      males (p < 0.005). The mean WEMWBS was 49.2 (95% confidence interval (CI): 48.3
      49.9). Low PA levels were related to lower WEMWBS scores, with statistically
      significant differences in WEMWBS demonstrated between low and moderate PA (p =
      0.05) and low and high PA (p = 0.001). Lack of time and perceived expense of
      facilities were common barriers to workplace PA. The main focus group finding was
      the impact of university culture on workplace PA and wellbeing. CONCLUSION:
      University staff demonstrate PA levels and a relationship between PA and
      wellbeing similar to the general population. Carefully designed strategies aimed
      at enhancing PA and wellbeing in university staff are required. The specific
      cultural and other barriers to workplace PA that exist in this setting should be
      considered. These results are being used to inform PA and wellbeing interventions
      whose effectiveness will be evaluated in future research.

PMID- 26194137
TI  - Completion of fit notes by GPs: a mixed methods study.
AB  - AIMS: The aim of this study was to investigate the completion of fit notes by UK
      general practitioners (GPs). A series of actual fit notes issued to employed
      patients were examined, and their GPs' reflections and experiences of fit note
      completion explored. METHODS: A mixed-methods design was used. Data were
      collected from copies of 94 fit notes issued to employed patients by 11 GPs, and
      from 86 questionnaires completed by these GPs reflecting on the fit notes they
      had issued. Face-to-face interviews were then conducted with each GP. RESULTS:
      Fit note completion is not meeting expectations for a number of reasons. These
      include the following: limited knowledge and awareness of the guidance in fit
      note completion; problems with the fit note format; lack of mandatory training in
      completing fit notes; lack of incentive to change practice; incomplete
      implementation of the electronic fit note; GPs' lack of confidence in, and doubts
      about the appropriateness of performing this role. CONCLUSION: If UK GPs are to
      continue their contractual responsibility for completing fit notes, further
      consideration of their education and training needs is urgently required.
      Weaknesses in the design and format of the fit note and the availability of the
      electronic version also need to be addressed.

PMID- 26194138
TI  - Helping Authors Organize Their Research: ORCID in the AGA Journals.

PMID- 26194139
TI  - Linking a Hepatology Clinical Service Line to Quality Improvement.

PMID- 26194140
TI  - Necrotizing herpes-simplex virus tonsillitis mimicking peritonsillar abscess.

PMID- 26194141
TI  - Determinants of readiness to adopt mHealth in a rural community of Bangladesh.
AB  - INTRODUCTION: Evidence in favor of mHealth for healthcare delivery in settings
      where trained health workforce is limited or unavailable is accumulating. With
      rapid growth in access to mobile phones and an acute shortage of health workforce
      in Bangladesh, mHealth initiatives are increasing with more than 20 current
      initiatives in place. "Readiness" is a crucial prerequisite to the successful
      implementation of telehealth programs. However, systematic assessment of the
      community readiness for mHealth-based services in the country is lacking. We
      report on a recent study describing the influence of community readiness for
      mHealth of a rural Bangladesh community. METHODS: A conceptual framework for
      mHealth readiness was developed, which included three categories: technological,
      motivational and resource readiness. This guided the questionnaire development
      for the survey conducted in the Chakaria sub-district of Bangladesh from November
      2012 to April 2013. Multivariate logistic regression was used to examine
      ownership of mobile phones, use of the technology, and knowledge regarding
      awareness of mHealth services as predictors of the community readiness to adopt
      mHealth. RESULTS: A total of 4915 randomly selected household members aged 18
      years and over completed the survey. The data explained the sub-categories of the
      readiness dimensions. In terms of access, 45% of respondents owned a mobile phone
      with ownership higher among males, younger participants and those in the highest
      socioeconomic quintiles. Results related to technological readiness showed that
      among mobile phone owners, 50% were aware of SMS but only sending and receiving
      SMS. Only 37% generally read the received SMS. Only 5% of respondents used the
      internet capabilities on their phone and 25% used voice messages. The majority
      (73%) of the participants were interested in joining mHealth programs in the
      future. Multivariate analysis showed that ownership of a mobile phone (aOR 1.3,
      95% CI 1.1-1.5), younger age (aOR 2.6, 95% CI 2.1-3.3), males (aOR 1.8, 95% CI
      1.6-2.1), educated respondents (11 years or more education) (aOR 11.1, 95% CI 6.2
      19.2) and those belonging to the highest socio-economic group (aOR 3.7, 95% CI
      2.9-4.7) were significantly independently associated with knowledge regarding
      awareness of current mHealth services. CONCLUSIONS: We developed a conceptual
      framework to assess community readiness for mHealth. We described three high
      level dimensions of readiness and have partially tested the conceptual framework
      in a rural sub-district in Bangladesh. We found that the community has some
      technological readiness but inequity was observed for human resource readiness
      and technological capabilities. The study population is motivated to use mHealth.
      Our conceptual framework is a promising tool to assist policy-makers in planning
      and implementing mHealth programs.

PMID- 26194142
TI  - Reply to 'Accurate measurement of the normality values of macroaggregated albumin
      lung perfusion scan in hepatopulmonary syndrome'.

PMID- 26194143
TI  - Relationship of quantitative parameters of myocardial perfusion SPECT and
      ventricular arrhythmia in patients receiving cardiac resynchronization therapy.
AB  - BACKGROUND: Ventricular arrhythmia is the major cause of sudden cardiac death for
      patients with heart failure, including those receiving implantation of cardiac
      resynchronization therapy (CRT). The purpose of this study was to assess the
      value of myocardial perfusion SPECT (MPS) in predicting ventricular arrhythmia
      for patients with CRT. METHODS AND METHODS: Fifty-one patients (35 males, mean
      age 64 +/- 12 years) who had received CRT for at least 6 months were enrolled for
      resting gated MPS. Three main quantitative parameters of MPS, including extent of
      myocardial scar, left ventricular ejection fraction (LVEF) and LV dyssynchrony
      (phase SD), were generated by Emory Cardiac Toolbox. Using the recorded
      ventricular arrhythmia in the device, including ventricular tachycardia (VT) and
      ventricular fibrillation (VF), as the primary end point, the value of
      quantitative parameters of MPS in predicting the development of VT/VF was
      assessed. RESULTS: Twenty (39 %) of the 51 patients developed VT/VF during the
      follow-up (15.3 +/- 12.7 months). The patients with VT/VF had significantly lower
      LVEF (24 +/- 12 vs. 36 +/- 17 %, p < 0.005), larger scar areas (36 +/- 19 vs. 22
      +/- 12 %, p < 0.05) and larger phase SD (57 degrees  +/- 20 degrees  vs. 43
      degrees  +/- 17 degrees , p < 0.01). When categorizing the patients by the median
      values of LVEF, scar and phase SD, univariate regression analysis showed that
      lower LVEF (<29 %), larger scar (>23 %) and larger phase SD (>50 degrees ) were
      related to the development of VT/VF (p = 0.006, 0.011 and 0.064, respectively).
      However, only LVEF was marginally significant as an independent predictor of
      VT//VF on multivariate regression analysis (p = 0.0573). Survival analysis with
      Kaplan-Meier curves showed that the survival probability for VT/VF in those with
      LVEF >29 %, scar areas <23 % and phase SD < 50 degrees  was significantly better
      than in the others (HR 5.16, 95 % CI 1.20-22.16) by log-rank test (chi (2) =
      5.9894, p = 0.014). CONCLUSION: Lower LVEF, larger scar and/or more dyssynchrony
      assessed by MPS were related to the development of ventricular arrhythmia for
      patients with CRT, and further defibrillator implantation may be considered for
      these patients.

PMID- 26194144
TI  - Can we shorten the overall treatment time in postoperative brachytherapy of
      endometrial carcinoma? Comparison of two brachytherapy schedules.
AB  - PURPOSE: To analyze vaginal-cuff relapses (VCR) and toxicity of two brachytherapy
      (BT) schedules in postoperative endometrial carcinoma and to correlate vaginal
      toxicity with vaginal-surface-EQD2Gy3 dose (VS-EQD2Gy3). METHODS/MATERIALS: 319
      patients (p) I-IIIC-Figo-stage were treated with 2 BT schedules. One schedule
      included 166p (Group-1) to whom 3 fractions (Fr) of 4-6Gy per week (w) of BT were
      administered after external beam radiotherapy (EBI) (125p) and 6Fr/2w of 4-6Gy in
      exclusive-BT (41p). The second schedule included 153p (Group-2) with BT
      administered daily with 2Fr/w of 5-6Gy after EBI (94p) and 5-6Gy/4Fr/w in
      exclusive-BT (59p). Doses were prescribed at 5mm from the vaginal surface.
      Toxicity was evaluated using RTOG scores for the rectum and bladder and objective
      LENT-SOMA scores for the vagina. STATISTICS: Chi-square, Fisher and Student's-t
      tests. RESULTS: Mean follow-up (months): Group-1: 66.55 (7.73-115.40), Group-2:
      41.49 (3.13-87.90). VCR: Group-1: 3p (1.88%); Group-2: 2p (1.3%). No differences
      were found between the two schedules comparing rectal (p=0.170), bladder
      (p=0.125) and vagina (p=0.680) late toxicities and comparing vagina EBI+BTp vs.
      exclusive-BTp (p=0.667). Significant differences in VS-EQD23Gy were observed
      considering EBI+BT (Groups 1+2) vs. exclusive-BT (Groups 1+2) (p<0.0001);
      nevertheless, no association was found between VS-EQD23Gy and vaginal
      complications. CONCLUSIONS: No differences were found between the two schedules.
      No association was found between vaginal toxicity and VS-EQD23Gy. Consequently,
      treatment with the least number of fractions is preferable.

PMID- 26194145
TI  - Facial reanimations: part II--long-standing paralyses.
AB  - Long-standing facial paralyses are those in which fibroadipose metaplasia of
      mimetic musculature has grown because of the time that has lapsed since the onset
      of the palsy: generally more than 18-24 months. Unlike the treatment of recent
      paralyses, to provide a neural input to reactivate the mimetic musculature is not
      enough. New healthy muscles must be transferred to the face. Operations may be
      subdivided into free-flap transplantations or masticatory muscle transpositions.
      The principles of treatment are correction of the asymmetry of the face by static
      means, and restoration of movements. Static correction of ptosis is achieved by
      deep-lifting, suspensions of fascia lata, and other procedures. Among movements,
      most efforts are concentrated on the restitution of smiling and closure of the
      eyelids. One of several techniques may be chosen after careful examination of the
      patient and paying close attention to their needs and expectations. Closure of
      the eyelids is generally achieved by a transposition of a double-belly temporalis
      flap or implantation of a gold/titanium lid plate. Other procedures are less
      used. Restoration of blinking remains impossible in most cases. The most popular
      techniques to restore smiling are rotation of a temporalis flap and transfer of a
      gracilis free flap with double innervation: both pros and cons must be
      considered. Surgery of the lower lip palsy is mainly based on limiting evident
      dragging upwards during smiling, because depressor function is difficult to
      achieve. Symmetry may also be reached by paralysing the lower lip on the other
      side. Movement of the forehead is a neglected area: reconstruction is possible,
      although the extent required seems disproportionate to the deficit. The need for
      ancillary surgery must be stressed. Only rarely are optimal results achieved
      without further fine-tuning of details. 

PMID- 26194146
TI  - Acidosis-induced downregulation of hepatocyte mitochondrial aquaporin-8 and
      ureagenesis from ammonia.
AB  - It has been proposed that, during metabolic acidosis, the liver downregulates
      mitochondrial ammonia detoxification via ureagenesis, a bicarbonate-consuming
      process. Since we previously demonstrated that hepatocyte mitochondrial aquaporin
      8 channels (mtAQP8) facilitate the uptake of ammonia and its metabolism into
      urea, we studied whether mtAQP8 is involved in the liver adaptive response to
      acidosis. Primary cultured rat hepatocytes were adapted to acidosis by exposing
      them to culture medium at pH 7.0 for 40 h. Control cells were exposed to pH 7.4.
      Hepatocytes exposed to acid medium showed a decrease in mtAQP8 protein expression
      (-30%, p < 0.05). Ureagenesis from ammonia was assessed by incubating the cells
      with (15)N-labeled ammonia and measuring (15)N-labeled urea synthesis by nuclear
      magnetic resonance. Reduced ureagenesis was found in acidified hepatocytes (-31%,
      p < 0.05). In vivo studies in rats subjected to 7 days acidosis also showed
      decreased protein expression of hepatic mtAQP8 (-50%, p < 0.05) and reduced liver
      urea content (-35%; p < 0.05). In conclusion, our in vitro and in vivo data
      suggest that hepatic mtAQP8 expression is downregulated in acidosis, a mechanism
      that may contribute to decreased ureagenesis from ammonia in response to
      acidosis. 

PMID- 26194147
TI  - The Double Helix: Applying an Ethic of Care to the Duty to Warn Genetic Relatives
      of Genetic Information.
AB  - Genetic testing reveals information about a patient's health status and
      predictions about the patient's future wellness, while also potentially
      disclosing health information relevant to other family members. With the
      increasing availability and affordability of genetic testing and the integration
      of genetics into mainstream medicine, the importance of clarifying the scope of
      confidentiality and the rules regarding disclosure of genetic findings to genetic
      relatives is prime. The United Nations International Declaration on Human Genetic
      Data urges an appreciation for principles of equality, justice, solidarity and
      responsibility in the context of genetic testing, including a commitment to
      honoring the privacy and security of the person tested. Considering this global
      mandate and recent professional statements in the context of a legal amendment to
      patient privacy policies in Australia, a fresh scrutiny of the legal history of a
      physician's duty to warn is warranted. This article inquiries whether there may
      be anything ethically or socially amiss with a potential future recommendation
      for health professionals or patients to universally disclose particular cancer
      predisposition genetic diagnosis to genetic family members. While much of the
      discussion remains applicable to all genetic diagnosis, the article focuses on
      the practice of disclosure within the context of BRCA1/2 diagnosis. An 'ethic of
      care' interpretation of legal tradition and current practice will serve to
      reconcile law and medical policy on the issue of physician disclosure of genetic
      results to family members without patient consent. 

PMID- 26194148
TI  - Parathyroid hormone and its receptor gene polymorphisms: implications in
      osteoporosis and in fracture healing.
AB  - Parathyroid glands secrete parathyroid hormone (PTH) which plays multiple roles
      in calcium homeostasis and in bone remodeling. Secretion of PTH is regulated by
      extracellular calcium levels and other humoral factors including
      1alpha,25(OH)2D3. PTH regulates gene expression and induces biological effects
      directly and indirectly. The human gene encoding PTH is located on chromosome 11.
      In this review, we study the diverse PTH along with its receptor gene
      polymorphisms and their association with osteoporosis and fracture healing.
      Genetic factors are associated with osteoporosis by influencing bone mineral
      density (BMD), bone turnover, calcium homeostasis, and susceptibility to
      osteoporotic fractures. Polymorphisms in genes encoding PTH may contribute to
      genetic regulation of BMD and thus susceptibility to fracture risk. PTH
      stimulates the proliferation of osteoprogenitor cells, production of alkaline
      phosphatise, and bone matrix proteins that contribute to hard callus formation
      and increases strength at the site of fractured bone. During remodeling, PTH
      promotes osteoclastogenesis restoring the original shape, structure, and
      mechanical strength of the bone. Some PTH polymorphisms have shown an association
      with fracture risk. Further research is needed to elucidate the relative
      importance of PTH genetics and the mechanisms of genetic contributions to gene
      gene interactions in the pathogenesis of osteoporosis and in fracture healing.

PMID- 26194149
TI  - Risk of Sjogren's syndrome in Taiwanese female adults with irregular menstrual
      cycles: a population-based case-control study.
AB  - Primary Sjogren's syndrome (pSS) is a progressive systemic autoimmune disorder
      with a strong female predominance. Hormonal influences are thought to play a role
      in the development of pSS. However, no studies have specifically evaluated the
      association between irregular menstrual cycles and pSS. Therefore, using a health
      claims database, this study investigated the risk of pSS in women with irregular
      menstrual cycles. We conducted a case-control study using the Taiwan's National
      Health Insurance Research Database. A total of 360 patients diagnosed with pSS
      (International Classification of Diseases, ninth revision, clinical modification,
      ICD-9-CM code 710.2) between 2001 and 2012 were identified. Controls were
      frequency-matched at a rate of 5:1 to the cases by five-year age interval and
      index year. Both cases and controls were retrospectively traced back until 2001
      for the diagnosis of irregular menstrual cycles (ICD-9-CM code 626.4). The risk
      of pSS was assessed using multivariate logistic regression analyses. Irregular
      menstrual cycles were significantly associated with pSS [adjusted odds ratio,
      (AOR) = 1.38, p = 0.027], after adjusted for insured amount, urbanization level,
      and thyroid disorder. In addition, when the data were stratified by three age
      categories, only the patients in the age category of 45-55 years showed
      significant association between irregular menstrual cycles and pSS (AOR = 1.74, p
      = 0.005). In this nationwide, population-based case-control study, we found a
      significant increased risk of pSS in female patients with irregular menstrual
      cycles, particularly those in their mid-forties to mid-fifties.

PMID- 26194150
TI  - Type 2 Diabetes Mellitus Patients' Healthcare Costs Related to Inpatient
      Hospitalizations: A Retrospective Administrative Claims Database Study.
AB  - INTRODUCTION: Diabetes-related healthcare costs are increasing in the United
      States, with inpatient hospitalization the largest component of medical
      expenditures. The aims of this study were to characterize hospitalized type 2
      diabetes mellitus (T2DM) patients, understand the relationship between
      hospitalization and healthcare costs, and explore treatment modification after
      inpatient hospitalization. METHODS: A retrospective cohort analysis of Humana
      Medicare Advantage and commercial members with T2DM was conducted. T2DM members
      were identified and assigned to three groups: (1) inpatient hospitalization (IPH)
      without a 30-day readmit (IPH group); (2) IPH with a 30-day readmission (IPH
      readmission group); and, (3) matched non-IPH group. Demographics, clinical
      characteristics, comorbidities and healthcare costs were measured based on
      enrollment data and claims. Descriptive statistics were used and the relationship
      between IPH and costs was assessed using generalized linear models. RESULTS: A
      total of 15,555 IPH patients, 1757 IPH readmission patients, and 17,312 matched
      non-IPH patients were included in the study. The IPH readmission group had the
      highest adjusted mean all-cause total costs ($76,806), followed by the IPH group
      ($42,011), and the non-IPH group ($9624). A similar trend was observed for
      adjusted all-cause mean medical and pharmacy costs. DM-related total healthcare
      costs were highest for the IPH readmission group ($13,714), followed by the IPH
      group ($7477), and non-IPH group ($1620). While overall therapy modification
      (discontinuation, addition, switch) was low, T2DM patients with an IPH (with or
      without a readmission) had greater rates of therapy modification relative to the
      non-IPH patients. CONCLUSION: Adjusted all-cause and DM-related total costs were
      greatest for IPH readmission patients. Rates of treatment modification within 10
      days of discharge after IPH were generally low. Identifying T2DM patients at high
      risk of readmission and employing methods to decrease that risk during the index
      hospitalization could have a significant impact on health system costs. FUNDING:
      Novo Nordisk.

PMID- 26194152
TI  - Detection and quantification of the opioid tramadol in urine using surface
      enhanced Raman scattering.
AB  - There is an on going requirement for the detection and quantification of illicit
      substances. This is in particular the case for law enforcement where portable
      screening methods are needed and there has been recent interest in breath tests
      for a range of narcotics. In this study we first developed surface enhanced Raman
      scattering (SERS) for the detection of tramadol in water and establish robust and
      reproducible methods based on silver hydroxylamine colloid. We used 0.5 M NaCl as
      the aggregating agent, with the pH ~ 7.0 and SERS data were collected immediately
      (i.e., the analyte association and colloid aggregation times were zero). The
      limit of detection was rather high and calculated to be 5 * 10(-4) M which would
      not be practical in the field. Undeterred we continued with spiking tramadol in
      artificial urine and found that no aggregating agent or modification of pH was
      necessary. Indeed aggregation occurred spontaneously due to the complexity of the
      medium which is rich in multiple salts, which are commonly used for SERS. We
      estimated the limit of detection in artificial urine to be 2.5 * 10(-6) M which
      is equivalent to 657.5 ng mL(-1) and very close to the levels typically found in
      individuals who use tramadol for pain relief. We believe this opens up
      opportunities for testing SERS in real world samples and this will be an area of
      future study. 

PMID- 26194153
TI  - COMBINATION OF COMPUTED TOMOGRAPHIC IMAGING CHARACTERISTICS OF MEDIAL
      RETROPHARYNGEAL LYMPH NODES AND NASAL PASSAGES AIDS DISCRIMINATION BETWEEN
      RHINITIS AND NEOPLASIA IN CATS.
AB  - Feline nasal diseases are a diagnostic challenge. The objective of this
      retrospective, cross-sectional study was to determine whether computed tomography
      (CT) imaging characteristics of the medial retropharyngeal lymph nodes (MRPLN),
      alone or in combination with CT imaging characteristics of the nasal passages,
      could aid in differentiation between rhinitis and nasal neoplasia. Cats were
      recruited from record archives at two veterinary facilities during the period of
      2008-2012. Selection criteria were presentation for chronic nasal discharge,
      contrast-enhanced CT of the head that included the MRPLN, and rhinoscopic nasal
      biopsy resulting in diagnosis of rhinitis or neoplasia. For each CT scan, two
      board-certified veterinary radiologists recorded MRPLN size, attenuation,
      heterogeneity, contrast-medium enhancement, margination, shape, presence of a
      lymph node hilus, perinodal fat, turbinate lysis, paranasal bone lysis, and nasal
      mass. Both readers were unaware of patient information at the time of CT
      interpretation. Thirty-four cats with rhinitis and 22 cats with neoplasia were
      included. Computed tomographic characteristics significantly associated with
      neoplasia included abnormal MRPLN hilus (OR 5.1), paranasal bone lysis (OR 5.6),
      turbinate lysis (5.6), mass (OR 26.1), MRPLN height asymmetry (OR 4.5), and
      decreased MRPLN precontrast heterogeneity (OR 7.0). The combined features
      predictive of neoplasia were a nasal mass with abnormal hilus (OR 47.7); lysis of
      turbinates/paranasal bones with abnormal MRPLN hilus (OR 16.2). Findings
      supported the hypothesis that combining CT features of the nasal passages and
      MRPLN aided in differentiating rhinitis from neoplasia in cats. 

PMID- 26194154
TI  - Salt Restriction in Diabetes.
AB  - There are no long-term interventions examining the effects of salt reduction in
      people with diabetes, and these are urgently required. Sodium reduction is
      controversial as it appears that an intake below 2.5 g and above 6 g/day of salt
      is associated with increased cardiovascular disease risk. However, pre-existing
      illness leading to a lower salt intake may confound the findings. Only a few
      studies have prospectively collected data on the sodium intake and excretion of
      people with diabetes and examined hard end points. In addition, future studies
      need to collect more data on food intake as well as coexistent illnesses to
      address potential confounding. The World Health Organization recommends a
      reduction to less than 5 g/day salt in adults. Given that the available evidence
      suggests that the salt intake of people with type 2 diabetes is generally well
      above 6 g/day it seems reasonable to ensure individuals with diabetes have an
      intake below 6 g/day. However, such recommendations need to be individualized. 

PMID- 26194155
TI  - Impact of Lifestyle Modification on Diabetic Kidney Disease.
AB  - Kidney disease is common in patients with type 1 and type 2 diabetes mellitus and
      is associated with adverse health outcomes, including progression to end-stage
      renal disease. In the general population, adherence to a healthy lifestyle is
      known to reduce the risk of cardiovascular events and death. Among individuals
      with diabetic kidney disease, modifications in lifestyle factors, including diet,
      physical activity, smoking habits, and body mass index, represent a promising
      cost-effective therapeutic adjunct to pharmacologic treatment of kidney disease
      incidence and progression. 

PMID- 26194156
TI  - From Individuals to International Policy: Achievements and Ongoing Needs in
      Diabetes Advocacy.
AB  - Diabetes impacts tens of millions of people in the United States of America and 9
      % of the worldwide population. Given the public health implications and economic
      burden of diabetes, the needs of people with diabetes must be addressed through
      strategic and effective advocacy efforts. Diabetes advocacy aims to increase
      public awareness about diabetes, raise funds for research and care, influence
      policy impacting people with diabetes, and promote optimal individual outcomes.
      We present a framework for diabetes advocacy activities by individuals and at the
      community, national, and international levels and identify challenges and gaps in
      current diabetes advocacy. Various groups have organized successful diabetes
      advocacy campaigns toward these goals, and lessons for further advancing diabetes
      advocacy can be learned from other health-related populations. Finally, we
      discuss the role of healthcare providers and mental/behavioral health
      professionals in advocacy efforts that can benefit their patients and the broader
      population of people with diabetes. 

PMID- 26194157
TI  - Global Health Justice and the Right to Health.
AB  - This paper reflects on Lawrence Gostin's Global Health Law. In so doing seeks to
      contribute to the debate about how global health justice is best conceived and
      achieved. Gostin's vision of global health is one which is communal and in which
      health is directly connected to other justice concerns. Hence the need for health
      in-all policies, and the importance of focusing on basic and communal health
      goods rather than high-tech and individual ones. This paper asks whether this
      broadly communal vision of global health justice is best served by making the
      right to health central to the project. It explores a number of reasons why
      rights-talk might be problematic in the context of health justice; namely,
      structurally, rights are individual and state-centric and politically, they are
      oppositional and better suited to single-issue campaigns. The paper argues that
      stripping rights of their individualist assumptions is difficult, and perhaps
      impossible, and hence alternative approaches, such as those Gostin endorses based
      on global public goods and health security, might deliver much, perhaps most,
      global health goods, while avoiding the problems of rights-talk. 

PMID- 26194159
TI  - Epistaxis: The role of arterial embolization.
AB  - Epistaxis is defined as flow of blood from the nasal fossae and is a common and
      benign disorder in the great majority of cases which does not require medical
      care. It may however become a genuine medical or surgical emergency because of
      the amount, repeated episodes or patient's medical vulnerability (such as
      coronary artery disease patients). Epistaxis may be either primary or a symptom
      of an underlying disease. Four levels of problems need to be answered faced with
      epistaxis: recognizing it, and in particular not missing "epistaxis" due to
      swallowed blood or venous hemorrhage, which falls outside of the scope of
      interventional radiology; establishing the amount and its repercussions,
      particularly as a decompensating factor in another disease; investigating its
      cause and in particular never missing a tumor (male adolescents); obtaining
      hemostasis. Epistaxis varies not only in type and cause but must be considered in
      its clinical context. Arterial embolization is a treatment of choice for severe
      refractory epistaxis and some hemorrhages. When carried out by trained operators,
      it is an effective method with few risks of complications and is increasingly
      being used in reference centers (Brinjikji et al.). It remains, however, a method
      which is less widely used than surgery, particularly in the United States where
      in a series of 69,410 patients treated over the last 10 years for refractory
      epistaxis, 92.6% underwent surgical ligation, 6.4% embolization and 1% combined
      treatments (Brinjikji et al.). Epistaxis is occasionally catastrophic and
      requires extremely urgent management. In each case, close collaboration with the
      surgeon, the presence of an intensive care anesthetist and at least sedation are
      all factors which improve management and therefore the results of embolization.
      All patients and/or their friends/close family should have given "reliable, clear
      and appropriate" information. 

PMID- 26194158
TI  - SM50 repeat-polypeptides self-assemble into discrete matrix subunits and promote
      appositional calcium carbonate crystal growth during sea urchin tooth
      biomineralization.
AB  - The two major proteins involved in vertebrate enamel formation and echinoderm sea
      urchin tooth biomineralization, amelogenin and SM50, are both characterized by
      elongated polyproline repeat domains in the center of the macromolecule. To
      determine the role of polyproline repeat polypeptides in basal deuterostome
      biomineralization, we have mapped the localization of SM50 as it relates to
      crystal growth, conducted self-assembly studies of SM50 repeat polypeptides, and
      examined their effect on calcium carbonate and apatite crystal growth. Electron
      micrographs of the growth zone of Strongylocentrotus purpuratus sea urchin teeth
      documented a series of successive events from intravesicular mineral nucleation
      to mineral deposition at the interface between tooth surface and odontoblast
      syncytium. Using immunohistochemistry, SM50 was detected within the cytoplasm of
      cells associated with the developing tooth mineral, at the mineral secreting
      front, and adjacent to initial mineral deposits, but not in muscles and
      ligaments. Polypeptides derived from the SM50 polyproline alternating hexa- and
      hepta-peptide repeat region (SM50P6P7) formed highly discrete, donut-shaped self
      assembly patterns. In calcium carbonate crystal growth studies, SM50P6P7 repeat
      peptides triggered the growth of expansive networks of fused calcium carbonate
      crystals while in apatite growth studies, SM50P6P7 peptides facilitated the
      growth of needle-shaped and parallel arranged crystals resembling those found in
      developing vertebrate enamel. In comparison, SM50P6P7 surpassed the PXX24
      polypeptide repeat region derived from the vertebrate enamel protein amelogenin
      in its ability to promote crystal nucleation and appositional crystal growth.
      Together, these studies establish the SM50P6P7 polyproline repeat region as a
      potent regulator in the protein-guided appositional crystal growth that occurs
      during continuous tooth mineralization and eruption. In addition, our studies
      highlight the role of species-specific polyproline repeat motifs in the formation
      of discrete self-assembled matrices and the resulting control of mineral growth. 

PMID- 26194160
TI  - Five Key Exercises for Upper Body Strength: A Guide for Persons With Paraplegia.

PMID- 26194161
TI  - Information/Education Page. Vision Problems After Traumatic Brain Injury.

PMID- 26194162
TI  - The mouse wellhaarig (we) mutations result from defects in epidermal-type
      transglutaminase 3 (Tgm3).
AB  - The recessive wellhaarig (we) mutations, named for the wavy coat and curly
      whiskers they generate in homozygotes, have previously been mapped on mouse
      Chromosome 2. To further limit the possible location of the we locus, we crossed
      hybrid (C57BL/6*AKR)F1, we(4J)/+ females with AKR, we(4J)/we(4J) mutant males to
      create a large backcross family that was typed for various microsatellite markers
      and single-nucleotide polymorphisms (SNPs) that distinguish strains AKR and B6.
      This analysis restricted the location of we(4J) between sites that flank only one
      gene known to be expressed in skin: epidermal-type transglutaminase 3 (Tgm3). To
      test Tgm3 as a candidate for the basis of the wellhaarig phenotype we took two
      approaches. First, we sequenced all Tgm3 coding regions in mice homozygous for
      four independent, naturally-occurring wellhaarig alleles (we, we(Bkr), we(3J) and
      we(4J)) and found distinct defects in three of these mutants. Second, we crossed
      mice homozygous for an induced mutant allele of Tgm3 (Tgm3(Btlr)) with mice
      heterozygous for one of the wellhaarig alleles we possess (we(4J) or we(Bkr)) to
      test for complementation. Because the progeny inheriting both a recessive we
      allele and a recessive Tgm3(Btlr) allele displayed wavy hair, we conclude that
      the classic wellhaarig mutations result from defects in Tgm3. 

PMID- 26194163
TI  - The combination of hypomethylating agents and histone deacetylase inhibitors
      produce marked synergy in preclinical models of T-cell lymphoma.
AB  - T-cell lymphomas (TCL) are aggressive lymphomas usually treated with CHOP
      (cyclophsophamide, doxorubicin, vincristine, prednisolone)-like regimens upfront.
      Recent data suggest that TCL are driven by epigenetic defects, potentially
      rendering them sensitive to epigenetic therapies. We explored the therapeutic
      merits of a combined epigenetic platform using histone deacetylase inhibitors
      (HDACIs) and DNA methyltransferase inhibitors (DNMT) in in vitro and in vivo
      models of TCL. The 50% inhibitory concentration (IC50 ) values revealed
      romidepsin was the most potent HDACI, with an IC50 in the low nanomolar range.
      The combination with a hypomethylating agent produced synergy across all cell
      lines, which was confirmed in cytotoxicity and apoptosis assays. An in vivo
      xenograft study demonstrated inhibition of tumour growth in the combination
      cohort compared to the single agent. Gene expression array and global methylation
      profiling revealed differentially expressed genes and modulated pathways for each
      of the single treatment conditions and the combination. Most of the effects
      induced by the single agent treatment were maintained in the combination group.
      In total, 944 unique genes were modulated by the combination treatment,
      supporting the hypothesis of molecular synergism. These data suggest combinations
      of hypomethylating agents and HDACIs are synergistic in models of TCL, which is
      supported at the molecular level.

PMID- 26194165
TI  - Electromagnetic interference shielding in 1-18 GHz frequency and electrical
      property correlations in poly(vinylidene fluoride)-multi-walled carbon nanotube
      composites.
AB  - Electromagnetic interference (EMI) shielding properties in the 1-18 GHz frequency
      range for multi-walled carbon nanotube (MWNT)-poly(vinylidene fluoride) (PVDF)
      composites are reported. A simple and gentle acid-treatment of MWNT showed a
      percolation threshold (PT) of 0.15 wt% in the PVDF matrix as against 0.35 wt% for
      unfunctionalized MWNT. Acid-treatment of MWNT significantly improves dispersion,
      interfacial adhesion with the matrix and the EMI shielding properties of PVDF
      composites. Further, the EMI shielding properties are correlated with the
      electrical properties. Using composite films of 0.3 mm thickness, the maximum
      shielding effectiveness (SET) values for 4 wt% unfunctionalized MWNT composites
      are found to be about 110, 45, 30, 26, and 58 dB for L (1-2 GHz), S (2-4 GHz), C
      (4-5.8 GHz), J (5.8-8 GHz), and X (8-12 GHz) bands, while the corresponding
      values for only 0.5 wt% acid functionalized MWNT composites are about 98, 45, 26,
      19, and 47 dB, respectively. The electrical conductivity for both the cases is
      ~10(-3) S cm(-1) and the weight contents of CNTs are higher than the PT for the
      respective composites. The comparable EMI SE and electrical conductivity values
      for both the composites at different weight fractions of CNTs suggest that there
      is a critical electrical conductivity above which the composites attain improved
      EMI shielding properties. Further, the shielding mechanism was found to be
      dominated by absorption loss. Therefore, the composites may also serve as a radar
      absorbing material. 

PMID- 26194164
TI  - Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae
      type b and meningococcal group C conjugate vaccines and components.
AB  - The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis
      serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was
      studied. By measuring the amount of polysaccharide and protein in the non
      adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be
      less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at
      concentrations relevant to licensed vaccine formulations and when equimolar. At
      neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier
      protein, with only weak binding of AlPO4 to CRM197 being observed. There was
      slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to
      CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP-Hib,
      where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib.
      At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind
      to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate
      ions reduced the binding of the conjugates to the adjuvants. These patterns of
      adjuvant adsorption can form the basis for future formulation studies with
      individual and combination vaccines containing saccharide-protein conjugates. 

PMID- 26194166
TI  - Non-native megaherbivores: the case for novel function to manage plant invasions
      on islands.
AB  - There is a heated debate about whether all non-native species are 'guilty until
      proven innocent', or whether some should be accepted or even welcomed. Further
      fanning the flames, I here present a case where introductions of carefully
      vetted, non-native species could provide a net conservation benefit. On many
      islands, native megaherbivores (flightless birds, tortoises) recently went
      extinct. Here, rewilding with carefully selected non-native species as ecological
      replacements is increasingly considered a solution, reinstating a herbivory
      regime that largely benefits the native flora. Based on these efforts, I suggest
      that restoration practitioners working on islands without a history of native
      megaherbivores that are threatened by invasive plants should consider introducing
      a non-native island megaherbivore, and that large and giant tortoises are ideal
      candidates. Such tortoises would be equally useful on islands where eradication
      of invasive mammals has led to increased problems with invasive plants, or on
      islands that never had introduced mammalian herbivores, but where invasive plants
      are a problem. My proposal may seem radical, but the reversibility of using giant
      tortoises means that nothing is lost from trying, and that indeed much is to be
      gained. As an easily regulated adaptive management tool, it represents an
      innovative, hypothesis-driven 'innocent until proven guilty' approach. 

PMID- 26194167
TI  - Low redundancy in seed dispersal within an island frugivore community.
AB  - The low species diversity that often characterizes island ecosystems could result
      in low functional redundancy within communities. Flying foxes (large fruit bats)
      are important seed dispersers of large-seeded species, but their redundancy
      within island communities has never been explicitly tested. In a Pacific
      archipelago, we found that flying foxes were the sole effective disperser of 57 %
      of the plant species whose fruits they consume. They were essential for the
      dispersal of these species either because they handled >90 % of consumed fruit,
      or were the only animal depositing seeds away from the parent canopy, or both.
      Flying foxes were especially important for larger-seeded fruit (>13 mm wide),
      with 76 % of consumed species dependent on them for dispersal, compared with 31 %
      of small-seeded species. As flying foxes decrease in abundance, they cease to
      function as dispersers long before they become rare. We compared the seed
      dispersal effectiveness (measured as the proportion of diaspores dispersed beyond
      parent crowns) of all frugivores for four plant species in sites where flying
      foxes were, and were not, functionally extinct. At both low and high abundance,
      flying foxes consumed most available fruit of these species, but the proportion
      of handled diaspores dispersed away from parent crowns (quality) was
      significantly reduced at low abundance. Since alternative consumers (birds,
      rodents and land crabs) were unable to compensate as dispersers when flying foxes
      were functionally extinct, we conclude that there is almost no redundancy in the
      seed dispersal function of flying foxes in this island system, and potentially on
      other islands where they occur. Given that oceanic island communities are often
      simpler than continental communities, evaluating the extent of redundancy across
      different ecological functions on islands is extremely important. 

PMID- 26194168
TI  - Consequences of waterlogging in cotton and opportunities for mitigation of yield
      losses.
AB  - Climatic variability, typified by erratic heavy-rainfall events, causes
      waterlogging in intensively irrigated crops and is exacerbated under warm
      temperature regimes on soils with poor internal drainage. Irrigated cotton is
      often grown in precisely these conditions, exposing it to waterlogging-induced
      yield losses after substantial summer rainfall. This calls for a deeper
      understanding of mechanisms of waterlogging tolerance and its relevance to
      cotton. Hence this review suggests possible causes of waterlogging-induced yield
      loss in cotton and approaches to improvement of waterlogging tolerance, drawing
      upon the slight body of published data in cotton and principles from other
      species. The yield penalty depends on soil type, phenological stage and
      cumulative period of root exposure to air-filled porosities below 10 %. Events in
      the soil include O2 deficiency in the root zone that changes the redox state of
      nutrients, making them unavailable (e.g. nitrogen) or potentially toxic for
      plants. Furthermore, root-derived hormones that are transported in the xylem have
      long been associated with oxygen deficits. These belowground effects (impaired
      root growth, nutrient uptake and transport, hormonal signalling) affect the
      shoots, interfering with canopy development, photosynthesis and radiation-use
      efficiency. Compared with the more waterlogging-tolerant cereals, cotton does not
      have identified adaptations to waterlogging in the root zone, forming no
      conspicuous root aerenchyma and having low fermentative activity. We speculate
      that these factors contribute substantially to the sensitivity of cotton to
      sustained periods of waterlogging. We discuss the impact of these belowground
      factors on shoot performance, photosynthesis and yield components. Management
      practices, i.e. soil aeration, scheduling irrigation and fertilizer application,
      can reduce waterlogging-induced damage. Limiting ethylene biosynthesis using anti
      ethylene agents and down-regulating expression of genes controlling ethylene
      biosynthesis are strong candidates to minimize yield losses in waterlogged cotton
      crops. Other key pathways of anoxia tolerance are also cited as potential tools
      towards waterlogging-tolerant cotton genotypes. 

PMID- 26194169
TI  - Reliability and Validity of the Spiritual Care-Giving Scale in a Turkish
      Population.
AB  - This study aimed to adapt an English version of the survey tool Spiritual Care
      Giving Scale for Turkish students and to evaluate its psychometric properties.
      Spiritual care is a central element of holistic nursing, but is not often made
      explicit in the theoretical and practical components of preregistration nursing
      programs. A composite scale will assist in identifying students' perceptions and
      issues to be addressed in curricula and practice settings in Turkey. The scale
      was composed of 35 items and five subscales. Cronbach's alpha reliability
      coefficient was .96, and item-total point correlations were between .37 and .77.
      In addition, split-half reliability coefficient was .88. The Spiritual Care
      Giving Scale was found to be a valid and reliable instrument for measuring the
      multifaceted perspectives of spirituality and spiritual care in practice by
      students. Further testing of this scale is required with other student
      populations and clinicians.

PMID- 26194170
TI  - Isolation and Characterization of Multipotential Mesenchymal Stromal Cells from
      Congenital Pseudoarthrosis of the Tibia: Case Report.
AB  - Congenital pseudoarthrosis of the tibia (CPT) is an uncommon disease whose
      etiology and pathogenesis is unknown. Several evidences suggest that decreased
      osteogenic capacities, impaired local vascularization, and microenvironment
      alterations may play a role in the pathogenesis of CPT. Additionally, it is not
      clear if the pathogenesis of this disease is related to the absence of cells with
      osteogenic capacity of differentiation. In this work, a two-year-old patient
      diagnosed with CPT underwent an orthopedic surgery to promote bone union in a
      pseudoarthrosis lesion. Tissue from CPT lesion was excised, and histological
      evaluation and tissue culture were performed. Histologic analysis of the soft CPT
      lesion showed the presence of highly cellular fibrous tissue, vascularization,
      and abundant extracellular matrix. Fusiform cells of mesenchymal appearance were
      observed but osteoblasts, osteoclasts, chondrocytes, and adipose cells were not
      found. There was no evidence of osteogenesis. CPT tissue cultured as explants
      showed, after one month of culture, evidence of osteogenesis, chondrogenesis, and
      adipogenesis. Cells isolated from explants of CPT tissue showed a fibroblast-like
      morphology and expressed the mesenchymal stromal cell (MSC) markers: CD105, CD73,
      and CD90 (CPT-MSC). Functional analysis showed that CPT-MSC differentiate, in
      vitro, into osteogenic, chondrogenic, and adipocytic cells. CPT-MSC expressed
      osteocalcin and agrecan. CPT-MSC produced collagen in the presence of ascorbic
      acid. MSC from BM of normal individuals were used as control. In summary, our
      results indicate that CPT tissue contains MSC with osteogenic capacity of
      differentiation. It is possible that CPT microenvironment may contribute to
      impair the osteogenic capacity of differentiation of CPT-MSC.

PMID- 26194171
TI  - A 32-year longitudinal study of alcohol consumption in Swedish women: Reduced
      risk of myocardial infarction but increased risk of cancer.
AB  - OBJECTIVE: To assess associations between the intake of different types of
      alcoholic beverages and the 32-year incidence of myocardial infarction, stroke,
      diabetes, and cancer, as well as mortality, in a middle-aged female population.
      DESIGN: Prospective study. SETTING: Gothenburg, Sweden, population about 430 000.
      SUBJECTS: Representative sample of a general population of women (1462 in total)
      aged 38 to 60 years in 1968-1969, followed up to the ages of 70 to 92 years in
      2000-2001. MAIN OUTCOME MEASURES: Associations between alcohol intake and later
      risk of mortality and morbidity from myocardial infarction, stroke, diabetes, and
      cancer, studied longitudinally. RESULTS: During the follow-up period, 185 women
      developed myocardial infarction, 162 developed stroke, 160 women became diabetic,
      and 345 developed cancer. Women who drank beer had a 30% lower risk (hazards
      ratio (HR) 0.70, 95% confidence interval (CI) 0.50-0.95) of developing myocardial
      infarcion and almost half the risk (HR 0.51 CI 0.33-0.80). A significant
      association between increased risk of death from cancer and high spirits
      consumption was also shown (hazards ratio [HR] 1.47, CI 1.06-2.05). CONCLUSIONS:
      Women with moderate consumption of beer had a reduced risk of developing
      myocardial infarction. High spirits consumption was associated with increased
      risk of cancer mortality.

PMID- 26194172
TI  - Early intervention for childhood overweight: A randomized trial in general
      practice.
AB  - OBJECTIVE: To evaluate the effect of two intervention modalities concerning
      overweight and obesity among children in general practice. DESIGN: Prospective
      randomized controlled trial. SETTING: A total of 60 general practices in the
      former County of Funen, Denmark. SUBJECTS: Overweight children, identified by
      International Obesity Task Force criteria, aged 5-9 years. INTERVENTION: Model 1
      with health consultations in general practice during a two-year period or Model
      2, an educational programme for the children and their families in addition to
      the health consultations. MAIN OUTCOME MEASURES: Change in body mass index (BMI)
      z-score in order to compare the results, independent of gender- and age-related
      changes over time. RESULTS: A total of 80 children were recruited with 35 and 45
      children allocated to Model 1 and Model 2, respectively. No significant
      differences were found in the change in BMI z-score (SDS) between the two groups.
      A decrease in the mean BMI z-score from baseline to study end of -0.20 (95%CI 
      0.38 to -0.01) in Model 1 and -0.26 (95%CI -0.44 to -0.09) in Model 2,
      respectively, was detected. The majority of the participants (2/3) continued in
      the study for more than one year in both models, with a mean of 12 consultations
      in general practice. CONCLUSION: In this particular setting the two intervention
      strategies against overweight and obesity did not differ significantly with
      regard to change in BMI z-scores.

PMID- 26194173
TI  - Alterations of the CD58 gene in classical Hodgkin lymphoma.
AB  - Immune evasion plays a central role in the pathophysiology of classical Hodgkin
      lymphoma (cHL). As mutations of the CD58 gene contribute to immune evasion of
      diffuse large B cell lymphoma tumor cells, we studied whether alterations of the
      CD58 gene also occur in Hodgkin and Reed/Sternberg (HRS) cells of cHL. Single
      nucleotide polymorphism chip analysis revealed homozygous deletions within the
      CD58 gene in two cHL cell lines (SUP-HD1 and U-HO1). Sequencing of the CD58 gene
      in seven cHL cell lines disclosed in addition a homozygous splice site mutation
      in cell line KM-H2. None of the three mutated lines expressed CD58 protein on
      their surface. Thus, three of seven cHL cell lines analyzed harbor destructive
      CD58 mutations. Molecular analysis of isolated HRS cells from 10 primary cases of
      cHL; however, did not reveal any case with a CD58 mutation. A FICTION study
      indicated heterozygous deletions of CD58 in 3 of 13 cHL analyzed. Overall, we
      report frequent inactivating mutations of CD58 in cHL cell lines, but their rare
      occurrence in primary HRS cells. As the three cHL cell lines with CD58 mutations
      were all established from HRS cells located in pleural effusions, i.e., outside
      the normal lymph node microenvironment, in end-stages of the disease, CD58
      inactivation in cHL might be predominantly prevalent to such situations.

PMID- 26194174
TI  - Feasibility and reproducibility of ShearWave(TM) elastography of fetal baboon
      organs.
AB  - OBJECTIVES: The purpose of this study was to assess the feasibility and
      reproducibility of transabdominal ShearWave(TM) elastography of fetal organs in
      pregnant baboons. MATERIALS AND METHODS: Fetal ultrasounds of all pregnant
      baboons in a single primate research center were performed prospectively during 9
      months. The visualization of fetal targeted organs (liver, proximal and distal
      lungs, brain white matter and periventricular gray matter) was initially
      performed using 2D ultrasound, and then elastography mode was activated. For each
      organ, three measurements were carried out by two operators. Intra-observer and
      inter-observer intra-class correlation coefficients (ICC) were calculated.
      RESULTS: During the study period (03/2013-12/2013), 21 pregnant baboons (21
      fetuses) were included. One to three ultrasound scans were performed for each
      fetus. The measurements were feasible by the two operators in all cases. The
      intra-observer and inter-observer ICC were 0.654, 95% CI (0.606 to 0.699) and
      0.645, 95% CI (0.553 to 0.721) respectively. CONCLUSION: Transabdominal
      ShearWave(TM) Elastography of fetal organs can be achieved in pregnant baboons.
      The intra-observer and inter-observer reproducibility is correct but vary
      according to the targeted organs.

PMID- 26194175
TI  - Trends in pesticide use on soybean, corn and cotton since the introduction of
      major genetically modified crops in the United States.
AB  - BACKGROUND: Genetically modified (GM) varieties of soybean, corn and cotton have
      largely replaced conventional varieties in the United States. The most widely
      used applications of GM technology have been the development of crops that are
      resistant to a specific broad-spectrum herbicide (primarily glyphosate) or that
      produce insecticidal compounds within the plant itself. With the widespread
      adoption of GM crops, a decline in the use of conventional pesticides was
      expected. RESULTS: There has been a reduction in the annual herbicide application
      rate to corn since the advent of GM crops, but the herbicide application rate is
      mostly unchanged for cotton. Herbicide use on soybean has increased. There has
      been a substantial reduction in the amount of insecticides used on both corn and
      cotton since the introduction of GM crops. CONCLUSIONS: The observed changes in
      pesticide use are likely to be the result of many factors, including the
      introduction of GM crops, regulatory restrictions on some conventional
      pesticides, introduction of new pesticide technologies and changes in farming
      practices. In order to help protect human and environmental health and to help
      agriculture plan for the future, more detailed and complete documentation on
      pesticide use is needed on a frequent and ongoing basis. Published 2015. This
      article is a U.S. Government work and is in the public domain in the USA.

PMID- 26194176
TI  - Nanometer-sized extracellular matrix coating on polymer-based scaffold for tissue
      engineering applications.
AB  - Surface modification can play a crucial role in enhancing cell adhesion to
      synthetic polymer-based scaffolds in tissue engineering applications. Here, we
      report a novel approach for layer-by-layer (LbL) fabrication of nanometer-size
      fibronectin and gelatin (FN-G) layers on electrospun fibrous poly(carbonate
      urethane)urea (PCUU) scaffolds. Alternate immersions into the solutions of
      fibronectin and gelatin provided thickness-controlled FN-G nano-layers (PCUU(FN
      G) ) which maintained the scaffold's 3D structure and width of fibrous bundle of
      PCUU as evidenced by scanning electron miscroscopy. The PCUU(FN-G) scaffold
      improved cell adhesion and proliferation of bladder smooth muscles (BSMCs) when
      compared to uncoated PCUU. The high affinity of PCUU(FN-G) for cells was further
      demonstrated by migration of adherent BSMCs from culture plates to the scaffold.
      Moreover, the culture of UROtsa cells, human urothelium-derived cell line, on
      PCUU(FN-G) resulted in an 11-15 MUm thick multilayered cell structure with cell
      to-cell contacts although many UROtsa cells died without forming cell connections
      on PCUU. Together these results indicate that this approach will aid in advancing
      the technology for engineering bladder tissues in vitro. Because FN-G nano-layers
      formation is based on nonspecific physical adsorption of fibronectin onto polymer
      and its subsequent interactions with gelatin, this technique may be applicable to
      other polymer-based scaffold systems for various tissue engineering/regenerative
      medicine applications.

PMID- 26194177
TI  - Effect of Nitrogen Fertilization and Harvest Time on Steviol Glycosides,
      Flavonoid Composition, and Antioxidant Properties in Stevia rebaudiana Bertoni.
AB  - This work investigated the effect of nitrogen fertilization and harvest time on
      the flavonoid composition and antioxidant properties of Stevia rebaudiana leaves.
      At the same time, changes in stevioside (Stev) and rebaudioside A (RebA) contents
      were recorded. A pot trial under open air conditions was set up, testing five N
      rates and three harvest times. The results showed that, by using an adequate N
      rate and choosing an appropriate harvest time, it was possible to significantly
      increase and optimize the bioactive compound levels. In particular, higher RebA,
      RebA/Stev ratio, total phenols and flavonoids, luteolin-7-O-glucoside, and
      apigenin-7-O-glucoside levels and antioxidant capacity were recorded by supplying
      150 kg N ha(-1). Reduced or increased N availability in comparison with N150 had
      no consistent effect on Stevia phytochemicals content. Significant correlations
      were also found between stevioside and some of the flavonoids, indicating a
      possible role of flavonoids in the stevioside metabolic pathway, which deserves
      more investigations. 

PMID- 26194178
TI  - Functionalized PDMS with Versatile and Scalable Surface Roughness Gradients for
      Cell Culture.
AB  - This manuscript describes a simple and versatile approach to engineering surface
      roughness gradients via combination of microfluidics and photopolymerization.
      Through UV-mediated polymerization, N-isopropylacrylamide with concentration
      gradients are successfully grafted onto PDMS surface, leading to diverse
      roughness degrees on the obtained PDMS substrate. Furthermore, the extent of
      surface roughness can be controllably regulated via tuning the flow rate ratio
      between the monomer solution and deionized water. Average roughness ranging from
      2.6+/-0.7 nm to 163.6+/-11.7 nm has been well-achieved in this work. Such PDMS
      samples are also demonstrated to be capable of working as supporting substrates
      for controlling cell adhesion or detachment. Because of the different degrees of
      surface roughness on a single substrate, our method provides an effective
      approach for designing advanced surfaces for cell culture. Finally, the
      thermosensitive property of N-isopropylacrylamide makes our sample furnish as
      another means for controlling the cell detachment from the substrates with
      correspondence to the surrounding temperature.

PMID- 26194179
TI  - Optimized exosome isolation protocol for cell culture supernatant and human
      plasma.
AB  - Extracellular vesicles represent a rich source of novel biomarkers in the
      diagnosis and prognosis of disease. However, there is currently limited
      information elucidating the most efficient methods for obtaining high yields of
      pure exosomes, a subset of extracellular vesicles, from cell culture supernatant
      and complex biological fluids such as plasma. To this end, we comprehensively
      characterize a variety of exosome isolation protocols for their efficiency, yield
      and purity of isolated exosomes. Repeated ultracentrifugation steps can reduce
      the quality of exosome preparations leading to lower exosome yield. We show that
      concentration of cell culture conditioned media using ultrafiltration devices
      results in increased vesicle isolation when compared to traditional
      ultracentrifugation protocols. However, our data on using conditioned media
      isolated from the Non-Small-Cell Lung Cancer (NSCLC) SK-MES-1 cell line
      demonstrates that the choice of concentrating device can greatly impact the yield
      of isolated exosomes. We find that centrifuge-based concentrating methods are
      more appropriate than pressure-driven concentrating devices and allow the rapid
      isolation of exosomes from both NSCLC cell culture conditioned media and complex
      biological fluids. In fact to date, no protocol detailing exosome isolation
      utilizing current commercial methods from both cells and patient samples has been
      described. Utilizing tunable resistive pulse sensing and protein analysis, we
      provide a comparative analysis of 4 exosome isolation techniques, indicating
      their efficacy and preparation purity. Our results demonstrate that current
      precipitation protocols for the isolation of exosomes from cell culture
      conditioned media and plasma provide the least pure preparations of exosomes,
      whereas size exclusion isolation is comparable to density gradient purification
      of exosomes. We have identified current shortcomings in common extracellular
      vesicle isolation methods and provide a potential standardized method that is
      effective, reproducible and can be utilized for various starting materials. We
      believe this method will have extensive application in the growing field of
      extracellular vesicle research. 

PMID- 26194180
TI  - Peripheral blood brain-derived neurotrophic factor in bipolar disorder: a
      comprehensive systematic review and meta-analysis.
AB  - Peripheral blood brain-derived neurotrophic factor (BDNF) has been proposed as a
      potential biomarker related to disease activity and neuroprogression in bipolar
      disorder, speculated to mirror alterations in brain expression of BDNF. The
      research area is rapidly evolving; however, recent investigations have yielded
      conflicting results with substantial variation in outcomes, highlighting the need
      to critically assess the state of current evidence. The aims of the study were to
      investigate differences in peripheral blood BDNF concentrations between bipolar
      disorder patients and healthy control subjects and between affective states in
      bipolar disorder patients, including assessment of the effect of treatment of
      acute episodes on BDNF levels. A systematic review of English language studies
      without considering publication status was conducted in PubMed (January 1950
      November 2014), Embase (1974-November 2014) and PsycINFO (1806-November 2014),
      and 35 studies comprising a total of 3798 participants were included in the meta
      analysis. The results indicated that crude peripheral blood BDNF levels may be
      lower in bipolar disorder patients overall (Hedges' g=-0.28, 95% CI: -0.51 to 
      0.04, P=0.02) and in serum of manic (g=-0.77, 95% CI: -1.36 to -0.18, P=0.01) and
      depressed (g=-0.87, 95% CI: -1.42 to -0.32, P=0.002) bipolar disorder patients
      compared with healthy control subjects. No differences in peripheral BDNF levels
      were observed between affective states overall. Longer illness duration was
      associated with higher BDNF levels in bipolar disorder patients. Relatively low
      study quality, substantial unexplained between-study heterogeneity, potential
      bias in individual studies and indications of publication bias, was observed and
      studies were overall underpowered. It could thus not be excluded that identified
      differences between groups were due to factors not related to bipolar disorder.
      In conclusion, limitations in the evidence base prompt tempered conclusions
      regarding the role of peripheral BDNF as a biomarker in bipolar disorder and
      substantially improving the quality of further research is warranted. 

PMID- 26194181
TI  - Evidence that the rab5 effector APPL1 mediates APP-betaCTF-induced dysfunction of
      endosomes in Down syndrome and Alzheimer's disease.
AB  - beta-Amyloid precursor protein (APP) and its cleaved products are strongly
      implicated in Alzheimer's disease (AD). Endosomes are highly active APP
      processing sites, and endosome anomalies associated with upregulated expression
      of early endosomal regulator, rab5, are the earliest known disease-specific
      neuronal response in AD. Here, we show that the rab5 effector APPL1 (adaptor
      protein containing pleckstrin homology domain, phosphotyrosine binding domain and
      leucine zipper motif) mediates rab5 overactivation in Down syndrome (DS) and AD,
      which is caused by elevated levels of the beta-cleaved carboxy-terminal fragment
      of APP (betaCTF). betaCTF recruits APPL1 to rab5 endosomes, where it stabilizes
      active GTP-rab5, leading to pathologically accelerated endocytosis, endosome
      swelling and selectively impaired axonal transport of rab5 endosomes. In DS
      fibroblasts, APPL1 knockdown corrects these endosomal anomalies. betaCTF levels
      are also elevated in AD brain, which is accompanied by abnormally high
      recruitment of APPL1 to rab5 endosomes as seen in DS fibroblasts. These studies
      indicate that persistent rab5 overactivation through betaCTF-APPL1 interactions
      constitutes a novel APP-dependent pathogenic pathway in AD. 

PMID- 26194182
TI  - De novo deleterious genetic variations target a biological network centered on
      Abeta peptide in early-onset Alzheimer disease.
AB  - We hypothesized that de novo variants (DNV) might participate in the genetic
      determinism of sporadic early-onset Alzheimer disease (EOAD, onset before 65
      years). We investigated 14 sporadic EOAD trios first by array-comparative genomic
      hybridization. Two patients carried a de novo copy number variation (CNV). We
      then performed whole-exome sequencing in the 12 remaining trios and identified 12
      non-synonymous DNVs in six patients. The two de novo CNVs (an amyloid precursor
      protein (APP) duplication and a BACE2 intronic deletion) and 3/12 non-synonymous
      DNVs (in PSEN1, VPS35 and MARK4) targeted genes from a biological network
      centered on the Amyloid beta (Abeta) peptide. We showed that this a priori
      defined genetic network was significantly enriched in amino acid-altering DNV,
      compared with the rest of the exome. The causality of the APP de novo duplication
      (which is the first reported one) was obvious. In addition, we provided evidence
      of the functional impact of the following three non-synonymous DNVs targeting
      this network: the novel PSEN1 variant resulted in exon 9 skipping in patient's
      RNA, leading to a pathogenic missense at exons 8-10 junction; the VPS35 missense
      variant led to partial loss of retromer function, which may impact neuronal APP
      trafficking and Abeta secretion; and the MARK4 multiple nucleotide variant
      resulted into increased Tau phosphorylation, which may trigger enhanced Abeta
      induced toxicity. Despite the difficulty to recruit Alzheimer disease (AD) trios
      owing to age structures of the pedigrees and the genetic heterogeneity of the
      disease, this strategy allowed us to highlight the role of de novo pathogenic
      events, the putative involvement of new genes in AD genetics and the key role of
      Abeta network alteration in AD. 

PMID- 26194184
TI  - Response of aboveground biomass and diversity to nitrogen addition along a
      degradation gradient in the Inner Mongolian steppe, China.
AB  - Although nitrogen addition and recovery from degradation can both promote
      production of grassland biomass, these two factors have rarely been investigated
      in combination. In this study, we established a field experiment with six N
      treatment (CK, 10, 20, 30, 40, 50 g N m(-2) yr(-1)) on five fields with different
      degradation levels in the Inner Mongolian steppe of China from 2011-2013. Our
      observations showed that while the external nitrogen increased the aboveground
      biomass in all five grasslands, the magnitude of the effects differed with the
      severity of degradation. Fields with a higher level of degradation tended to have
      a higher saturation value (20 g N m(-2) yr(-1)) than those with a lower
      degradation level ( < 10 g N m(-2) yr(-1)). After three years of experimentation,
      species richness showed little change across degradation levels. Among the four
      functional groups of grasses, sedges, forbs and legumes, grasses shared the most
      similar response patterns with those of the whole community, demonstrating the
      predominant role that they play in the restoration of grassland under a stimulus
      of nitrogen addition.

PMID- 26194183
TI  - Elevated peripheral cytokines characterize a subgroup of people with
      schizophrenia displaying poor verbal fluency and reduced Broca's area volume.
AB  - Previous studies on schizophrenia have detected elevated cytokines in both brain
      and blood, suggesting neuroinflammation may contribute to the pathophysiology in
      some cases. We aimed to determine the extent to which elevated peripheral
      cytokine messenger RNA (mRNA) expression: (1) characterizes a subgroup of people
      with schizophrenia and (2) shows a relationship to cognition, brain volume and/or
      symptoms. Forty-three outpatients with schizophrenia or schizoaffective disorder
      and matched healthy controls were assessed for peripheral cytokine mRNAs
      (interleukin (IL)-1beta, IL-2, IL-6, IL-8 and IL-18), intelligence quotient,
      memory and verbal fluency, symptom severity and cortical brain volumes integral
      to language (that is, Broca's and Wernicke's areas). IL-1beta mRNA levels were
      28% increased in schizophrenia compared with controls (t(82)=2.64, P<0.01). Using
      a two-step clustering procedure, we identified a subgroup of people displaying
      relatively elevated cytokine mRNA levels (17/43 people with schizophrenia and
      9/42 controls). Individuals with schizophrenia in the elevated cytokine subgroup
      performed significantly worse than the low-cytokine subgroup on verbal fluency
      (F(1,40)=15.7, P<0.001). There was a 17% volume reduction of the left pars
      opercularis (POp) (Broca's area) in patients with elevated cytokines compared
      with patients with lower cytokines (F(1,29)=9.41, P=0.005). Negative linear
      relationships between IL-1beta mRNA levels and both verbal fluency and left POp
      volume were found in schizophrenia. This study is among the first to link blood
      biomarkers of inflammation with both cognitive deficits and brain volume
      reductions in people with schizophrenia, supporting that those with elevated
      cytokines represent a neurobiologically meaningful subgroup. These findings raise
      the possibility that targeted anti-inflammatory treatments may ameliorate
      cognitive and brain morphological abnormalities in some people with
      schizophrenia.

PMID- 26194187
TI  - Identification of key factors affecting the water pollutant concentration in the
      sluice-controlled river reaches of the Shaying River in China via statistical
      analysis methods.
AB  - The construction of sluices creates a strong disturbance in water environmental
      factors within a river. The change in water pollutant concentrations of sluice
      controlled river reaches (SCRRs) is more complex than that of natural river
      segments. To determine the key factors affecting water pollutant concentration
      changes in SCRRs, river reaches near the Huaidian Sluice in the Shaying River of
      China were selected as a case study, and water quality monitoring experiments
      based on different regulating modes were implemented in 2009 and 2010. To
      identify the key factors affecting the change rates for the chemical oxygen
      demand of permanganate (CODMn) and ammonia nitrogen (NH3-N) concentrations in the
      SCRRs of the Huaidian Sluice, partial correlation analysis, principal component
      analysis and principal factor analysis were used. The results indicate four
      factors, i.e., the inflow quantity from upper reaches, opening size of sluice
      gates, water pollutant concentration from upper reaches, and turbidity before the
      sluice, which are the common key factors for the CODMn and NH3-N concentration
      change rates. Moreover, the dissolved oxygen before a sluice is a key factor for
      the permanganate concentration from CODMn change rate, and the water depth before
      a sluice is a key factor for the NH3-N concentration change rate. Multiple linear
      regressions between the water pollutant concentration change rate and key factors
      were established via multiple linear regression analyses, and the quantitative
      relationship between the CODMn and NH3-N concentration change rates and key
      affecting factors was analyzed. Finally, the mechanism of action for the key
      factors affecting the water pollutant concentration changes was analyzed. The
      results reveal that the inflow quantity from upper reaches, opening size of
      sluice gates, permanganate concentration from CODMn from upper reaches and
      dissolved oxygen before the sluice have a negative influence and the turbidity
      before the sluice has a positive influence on the permanganate concentration from
      CODMn change rates and that the opening size of sluice gates, NH3-N concentration
      from upper reaches, and water depth before the sluice have a negative influence
      and the inflow quantity from upper reaches and turbidity before the sluice have a
      positive influence on the NH3-N concentration change rates, which provides a
      scientific grounding for pollution control and sluice operations in SCRRs. 

PMID- 26194186
TI  - TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus
      preoperative chemoradiation plus perioperative ECF chemotherapy for resectable
      gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC
      CTG).
AB  - BACKGROUND: The optimal management of patients with resectable gastric cancer
      continues to evolve in Western countries. Following publication of the US
      Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two
      standards of care for adjuvant therapy in resectable gastric cancer, at least in
      the Western world: postoperative chemoradiotherapy and perioperative
      epirubicin/cisplatin/fluorouracil (ECF) chemotherapy. We hypothesize that adding
      chemoradiation to standard perioperative ECF chemotherapy will achieve further
      survival gains. We also believe there are advantages to administering
      chemoradiation in the preoperative rather than postoperative setting. In this
      article, we describe the TOPGEAR trial, which is a randomised phase III trial
      comparing control arm therapy of perioperative ECF chemotherapy with experimental
      arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy.
      METHODS/DESIGN: Eligible patients with resectable adenocarcinoma of the stomach
      or gastroesophageal junction will be randomized to receive either perioperative
      chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or
      perioperative chemotherapy plus preoperative chemoradiation. In the
      chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to
      surgery, and then following surgery 3 further cycles of ECF are given. The trial
      is being conducted in two Parts; Part 1 (phase II component) has recruited 120
      patients with the aim of assessing feasibility, safety and preliminary efficacy
      of preoperative chemoradiation. Part 2 (phase III component) will recruit a
      further 632 patients to provide a total sample size of 752 patients. The primary
      endpoint of the phase III trial is overall survival. The trial includes quality
      of life and biological substudies, as well as a health economic evaluation. In
      addition, the trial incorporates a rigorous quality assurance program that
      includes real time central review of radiotherapy plans and central review of
      surgical technique. DISCUSSION: TOPGEAR is an international, intergroup
      collaboration led by the Australasian Gastro-Intestinal Trials Group (AGITG), in
      collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European
      Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical
      Trials Group. It addresses a globally significant question that will help inform
      future international standards for clinical practice in resectable gastric
      cancer. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12609000035224 . Registered 30 May 2009.

PMID- 26194185
TI  - Development and external validation of nomograms predicting distant metastases
      and overall survival after neoadjuvant chemotherapy and surgery for patients with
      nonmetastatic osteosarcoma: A multi-institutional study.
AB  - BACKGROUND: In this era of individualized cancer treatment, data that could be
      applied to predicting the survival of patients with osteosarcoma are still
      limited because of the rarity of the disease and the difficulty in accumulating a
      sufficient number of patients. Therefore, a multi-institutional collaboration was
      implemented to develop and externally validate nomograms that would predict
      metastasis-free survival (MFS) and overall survival (OAS) for patients with
      nonmetastatic osteosarcoma. METHODS: This study retrospectively examined 1070
      patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic
      osteosarcoma. Data from Japanese patients (n = 557) were used to develop
      multivariate nomograms based on Cox regression. Six clinical and pathologic
      variables were built into nomograms estimating the probability of MFS and OAS 3
      and 5 years after diagnosis. The model was internally validated for
      discrimination and calibration with bootstrap resampling and was externally
      validated with an independent patient cohort from Korea (n = 513). RESULTS: A
      patient's age, tumor site, and histologic response were found to have a stronger
      influence on MFS and OAS in the model than sex, tumor size, or pathologic
      fracture. The nomograms and calibration plots based on these results well
      predicted the probability of MFS (concordance index, 0.631) and OAS (concordance
      index, 0.679). The concordance indices for external validation were 0.682 for MFS
      and 0.665 for OAS. CONCLUSIONS: The nomograms were externally validated and
      verified to be useful for the prediction of MFS and OAS and for the assessment of
      the postoperative prognosis. They can be used for counseling patients and for
      establishing appropriate surveillance strategies after surgery.

PMID- 26194188
TI  - Enhancement of insulin-mediated rat muscle glucose uptake and microvascular
      perfusion by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside.
AB  - BACKGROUND: Insulin-induced microvascular recruitment is important for optimal
      muscle glucose uptake. 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
      (AICAR, an activator of AMP-activated protein kinase), can also induce
      microvascular recruitment, at doses that do not acutely activate glucose
      transport in rat muscle. Whether low doses of AICAR can augment physiologic
      insulin action is unknown. In the present study we used the euglycemic
      hyperinsulinemic clamp to assess whether insulin action is augmented by low dose
      AICAR. METHODS: Anesthetized rats were studied during saline infusion or
      euglycemic insulin (3 mU/kg/min) clamp for 2 h in the absence or presence of
      AICAR for the last hour (5 mg bolus followed by 3.75 mg/kg/min). Muscle glucose
      uptake (R'g) was determined radioisotopically with (14)C-2-deoxyglucose and
      muscle microvascular perfusion by contrast-enhanced ultrasound with microbubbles.
      RESULTS: AICAR did not affect blood glucose, or lower leg R'g, although it
      significantly (p < 0.05) increased blood lactate levels and augmented muscle
      microvascular blood volume via a nitric oxide synthase dependent pathway. Insulin
      increased femoral blood flow, whole body glucose infusion rate (GIR), R'g,
      hindleg glucose uptake, and microvascular blood volume. Addition of AICAR during
      insulin infusion increased lactate production, further increased R'g in Type IIA
      (fast twitch oxidative) and IIB (fast twitch glycolytic) fiber containing
      muscles, and hindleg glucose uptake, but decreased R'g in the Type I (slow twitch
      oxidative) fiber muscle. AICAR also decreased GIR due to inhibition of insulin
      mediated suppression of hepatic glucose output. AICAR augmented insulin-mediated
      microvascular perfusion. CONCLUSIONS: AICAR, at levels that have no direct effect
      on muscle glucose uptake, augments insulin-mediated microvascular blood flow and
      glucose uptake in white fiber type muscles. Agents targeted to endothelial AMPK
      activation are promising insulin sensitizers, however, the decrease in GIR and
      the propensity to increase blood lactate cautions against AICAR as an acute
      insulin sensitizer.

PMID- 26194189
TI  - Breast cancer screening disparities among urban immigrants: a population-based
      study in Ontario, Canada.
AB  - BACKGROUND: Breast cancer is one of the leading cause of mortality and morbidity
      in Canada. Screening is the most promising approach in identification and
      treatment of the disease at early stage of its development. Research shows higher
      rate of breast cancer mortality among ethno-racial immigrant women despite their
      lower incidence which suggests disparities in mammography screening. This study
      aimed to compare the prevalence of appropriate mammography screening among
      immigrant and native borne women and determine predicators of low mammography
      screening. METHODS: We conducted secondary data analyses on Ontario linked social
      and health databases to determine the proportion of women who were screened
      during the two-year period of 2010-2012 among 1.4 million screening-eligible
      women living in urban centres in Ontario. We used multivariate Poisson regression
      to adjust for various socio-demographic, health care-related and migration
      related variables. RESULTS: 64% of eligible women were appropriately screened.
      Screening rates were lowest among new and recent immigrants compared to referent
      group (Canadian-born women and immigrant who arrived before 1985) (Adjusted Rate
      Ratio (ARR) (0.87, 95% CI 0.85-0.88 for new immigrants and 0.90, 95% CI 0.89-0.91
      for recent immigrants. Factors that were associated with lower rates of screening
      included living in low-income neighborhoods, having a male physician, having
      internationally-trained physician and not being enrolled in primary care patient
      enrolment models. Those not enrolled were 22% less likely to be screened compared
      to those who were (ARR 0.78, 95% CI 0.77-0.79). CONCLUSION: To enhance immigrant
      women screening rates efforts should made to increase their access to primary
      care patient enrolment models and preferably female health professionals. Support
      should be provided to interventions that address screening barriers like
      language, acculturation limitations and knowledge deficit. Health professionals
      need to be educated and take an active role in offering screening guidelines
      during health encounters.

PMID- 26194190
TI  - Evolutionary engineering of a wine yeast strain revealed a key role of inositol
      and mannoprotein metabolism during low-temperature fermentation.
AB  - BACKGROUND: Wine produced at low temperature is often considered to improve
      sensory qualities. However, there are certain drawbacks to low temperature
      fermentations: e.g. low growth rate, long lag phase, and sluggish or stuck
      fermentations. Selection and development of new Saccharomyces cerevisiae strains
      well adapted at low temperature is interesting for future biotechnological
      applications. This study aimed to select and develop wine yeast strains that well
      adapt to ferment at low temperature through evolutionary engineering, and to
      decipher the process underlying the obtained phenotypes. RESULTS: We used a pool
      of 27 commercial yeast strains and set up batch serial dilution experiments to
      mimic wine fermentation conditions at 12  degrees C. Evolutionary engineering was
      accomplished by using the natural yeast mutation rate and mutagenesis procedures.
      One strain (P5) outcompeted the others under both experimental conditions and was
      able to impose after 200 generations. The evolved strains showed improved growth
      and low-temperature fermentation performance compared to the ancestral strain.
      This improvement was acquired only under inositol limitation. The transcriptomic
      comparison between the evolved and parental strains showed the greatest up
      regulation in four mannoprotein coding genes, which belong to the DAN/TIR family
      (DAN1, TIR1, TIR4 and TIR3). Genome sequencing of the evolved strain revealed the
      presence of a SNP in the GAA1 gene and the construction of a site-directed mutant
      (GAA1 (Thr108)) in a derivative haploid of the ancestral strain resulted in
      improved fermentation performance. GAA1 encodes a GPI transamidase complex
      subunit that adds GPI, which is required for inositol synthesis, to newly
      synthesized proteins, including mannoproteins. CONCLUSIONS: In this study we
      demonstrate the importance of inositol and mannoproteins in yeast adaptation at
      low temperature and the central role of the GAA1 gene by linking both
      metabolisms.

PMID- 26194192
TI  - The copper-catalyzed synthesis of beta-trifluoromethylated acrylonitriles and
      trifluoromethyl-substituted 2H-azirines.
AB  - The direct assembly of acrylonitriles and valuable 2H-azirines from readily
      available starting materials is described. This novel alkyne difunctionalization
      reaction proceeded under mild reaction conditions. Considering the versatile
      roles of 2H-azirines, this work paves the way for further modification into
      various heterocycles. 

PMID- 26194193
TI  - A new class of thermotropic lanthanidomesogens: Eu(III) nitrate complexes with
      mesogenic 4-pyridone ligands.
AB  - A new class of thermotropic lanthanidomesogens has been designed and prepared.
      They are based on 4-pyridone ligands that possess mesogenic cyanobiphenyl groups
      attached to the 4-pyridone unit via a flexible long alkyl spacer and show a very
      high thermal stability (decomposition temperatures near 300  degrees C).
      Depending on the alkyl length spacer, these complexes exhibit a SmA phase with
      transition temperatures influenced by the number of mesogenic groups employed and
      the spacer length. 

PMID- 26194191
TI  - Loss of Stromal IMP1 Promotes a Tumorigenic Microenvironment in the Colon.
AB  - The colon tumor microenvironment is becoming increasingly recognized as a complex
      but central player in the development of many cancers. Previously, we identified
      an oncogenic role for the mRNA-binding protein IMP1 (IGF2BP1) in the epithelium
      during colon tumorigenesis. In the current study, we reveal the contribution of
      stromal IMP1 in the context of colitis-associated colon tumorigenesis.
      Interestingly, stromal deletion of Imp1 (Dermo1Cre;Imp1(LoxP/LoxP), or
      Imp1(DeltaMes)) in the azoxymethane/dextran sodium sulfate (AOM/DSS) model of
      colitis-associated cancer resulted in increased tumor numbers of larger size and
      more advanced histologic grade than controls. In addition, Imp1(DeltaMes) mice
      exhibited a global increase in protumorigenic microenvironment factors, including
      enhanced inflammation and stromal components. Evaluation of purified mesenchyme
      from AOM/DSS-treated Imp1(DeltaMes) mice demonstrated an increase in hepatocyte
      growth factor (HGF), which has not been associated with regulation via IMP1.
      Genetic knockdown of Imp1 in human primary fibroblasts confirmed an increase in
      HGF with Imp1 loss, demonstrating a specific, cell-autonomous role for Imp1 loss
      to increase HGF expression. Taken together, these data demonstrate a novel tumor
      suppressive role for IMP1 in colon stromal cells and underscore an exquisite,
      context-specific function for mRNA-binding proteins, such as IMP1, in disease
      states. IMPLICATIONS: The tumor-suppressive role of stromal IMP1 and its ability
      to modulate protumorigenic factors suggest that IMP1 status is important for the
      initiation and growth of epithelial tumors.

PMID- 26194194
TI  - Effects of acute administration of melatonin on attentional, executive, and
      working memory processes in rats.
AB  - Melatonin is a potential candidate for additive therapy in cancer,
      neurodegenerative, and mental disorders requiring administration during the
      activity phase. Nevertheless, because melatonin has mostly been used as a
      hypnotic, less is known about its cognitive effects. In this study, we
      investigated the effects of acute administration of melatonin on executive,
      attentional, and working memory processes in rats during the activity phase.
      Three doses of melatonin (6, 18, or 36 mg/kg) were tested and compared to a
      saline control group in two behavioral tests: the Attentional Set Shifting task
      (for attentional and executive processes assessment) and the Spontaneous
      Alternation test in a Y-maze (for working memory assessment). Our results
      revealed that, up to 36 mg/kg, the acute administration dose of melatonin did not
      alter the attentional or executive processes, nor the working memory in rats.
      Consequently, this result may be encouraging for the use of melatonin in additive
      therapy during the activity phase. 

PMID- 26194195
TI  - A multimodal neuroimaging study of a case of crossed nonfluent/agrammatic primary
      progressive aphasia.
AB  - Crossed aphasia has been reported mainly as post-stroke aphasia resulting from
      brain damage ipsilateral to the dominant right hand. Here, we described a case of
      a crossed nonfluent/agrammatic primary progressive aphasia (nfvPPA), who
      developed a corticobasal syndrome (CBS). We collected clinical, cognitive, and
      neuroimaging data for four consecutive years from a 55-year-old right-handed lady
      (JV) presenting with speech disturbances. 18-fluorodeoxyglucose positron emission
      tomography ((18)F-FDG PET) and DaT-scan with (123)I-Ioflupane were obtained.
      Functional MRI (fMRI) during a verb naming task was acquired to characterize
      patterns of language lateralization. Diffusion tensor MRI was used to evaluate
      white matter damage within the language network. At onset, JV presented with
      prominent speech output impairment and right frontal atrophy. After 3 years,
      language deficits worsened, with the occurrence of a mild agrammatism. The
      patient also developed a left-sided mild extrapyramidal bradykinetic-rigid
      syndrome. The clinical picture was suggestive of nfvPPA with mild left-sided
      extrapyramidal syndrome. At this time, voxel-wise SPM analyses of (18)F-FDG PET
      and structural MRI showed right greater than left frontal hypometabolism and
      damage, which included the Broca's area. DaT-scan showed a reduced uptake in the
      right striatum. FMRI during naming task demonstrated bilateral language
      activations, and tractography showed right superior longitudinal fasciculus (SLF)
      involvement. Over the following year, JV became mute and developed frank left
      sided motor signs and symptoms, evolving into a CBS clinical picture. Brain
      atrophy worsened in frontal areas bilaterally, and extended to temporo-parietal
      regions, still with a right-sided asymmetry. Tractography showed an extension of
      damage to the left SLF and right inferior longitudinal fasciculus. We report a
      case of crossed nfvPPA followed longitudinally and studied with advanced
      neuroimaging techniques. The results highlight a complex interaction between
      individual premorbid developmental differences and the clinical phenotype.

PMID- 26194196
TI  - A novel OPA1 mutation causing variable age of onset autosomal dominant optic
      atrophy plus in an Australian family.
AB  - Pathogenic mutations in the OPA1 gene can be associated with Autosomal Dominant
      Optic Atrophy (ADOA). In approximately 20 % of patients with OPA1 mutations, a
      more complex neurodegenerative disorder with extraocular manifestations, known as
      ADOA Plus, can arise. 12 members of a multigenerational family were assessed
      clinically and screened for a genetic mutation in OPA1. Eight family members
      displayed manifestations consistent with ADOA Plus and four did not. Affected
      members of the oldest available generation displayed the most severe phenotype,
      which included severe optic atrophy, deafness, ptosis, ophthalmoplegia, proximal
      myopathy, neuropathy and ataxia. The next generation was less severely affected
      but several members displayed manifestations only after the fifth decade. Genetic
      analysis revealed a heterozygous variant in the OPA1 gene (c.1053T>A,
      p.Asp351Glu) that segregated with disease. The affected family members described
      here exhibited visual loss later than is typical for OPA1-related disease, as
      well as later onset of other neurological abnormalities in the fifth or sixth
      decades of life that progressed to severe neurological disability by the seventh
      decade. These findings expand the clinical spectrum of OPA1-related disease
      associated with a novel OPA1 mutation.

PMID- 26194197
TI  - Absence of HINT1 mutations in a UK and Spanish cohort of patients with inherited
      neuropathies.
AB  - Biallelic mutations in the HINT1 gene were recently identified as the cause of
      axonal neuropathy with neuromyotonia. It has been suggested that HINT1 mutations
      may indeed account for 11% of all inherited neuropathies with autosomal recessive
      inheritance. However, 81% of patients HINT1-related neuropathies reported to date
      are originally from five European countries and the global prevalence of the
      disorder is still unknown. In our study, we aimed to determine the frequency of
      HINT1 mutations by direct sequencing in a cohort of 152 patients with inherited
      neuropathies from the UK and Spain, where no cases have been described to date.
      We failed to identify patients with clinical myotonia, neuromyotonia or
      pathogenic mutations in HINT1. Our results support that HINT1-related
      neuropathies are not homogeneously distributed among European populations, which
      may be explained by founder effects. This geographical variability also
      underlines the importance of considering the ethnic background when screening for
      mutations in neuropathy-related genes.

PMID- 26194198
TI  - Rituximab as first-line therapy in neuromyelitis optica: efficiency and
      tolerability.
AB  - Neuromyelitis optica (NMO) is a life-threatening disease without any validated
      treatment strategy. Recent retrospective studies suggested the efficacy of B cell
      depletion without any distinction between first-line or rescue therapy. To assess
      whether rituximab as first-line therapy in NMO could efficiently control the
      occurrence of relapses. A retrospective analysis of NMO patients from NOMADMUS
      network found 32 patients receiving rituximab as first-line therapy. Main
      measures were number of relapse-free patients, changes in the annualized relapse
      rate (ARR), and changes in the EDSS. Tolerance was reported. At baseline, NMO
      patients were 45 +/- 12.1 years old, with a sex ratio of 5.4, and 87.5 % of them
      had AQP4 antibodies. The median disease duration was 6.5 months (1-410), the mean
      EDSS was 5.8 +/- 2.4 and the mean ARR was 3.8 +/- 4.3. After rituximab with a
      mean follow-up of 28.7 +/- 21 months, twenty-seven patients (84.3 %) were relapse
      free. Patients presented a 97 % decrease of ARR (p = 0.00001). EDSS decreased
      significantly to 3.9 +/- 2.6 (p = 0.01). No relevant side effect was noted. New
      retrospective data are presented on RTX use in NMOSD. When used as first-line
      therapy RTX is highly effective and well tolerated.

PMID- 26194199
TI  - Speech and voice disorders in patients with psychogenic movement disorders.
AB  - Psychogenic speech and voice disorders (PSVDs) may occur in isolation but more
      typically are encountered in the setting of other psychogenic disorders. We aimed
      to characterize the phenomenology, frequency, and correlates of PSVDs in a cohort
      of patients with psychogenic movement disorders (PMDs). We studied 182
      consecutive patients with PMDs, 30 of whom (16.5 %) also exhibited PSVD.
      Stuttering was the most common speech abnormality (n = 16, 53.3 %), followed by
      speech arrests (n = 4, 13.3 %), foreign accent syndrome (n = 2, 6.6 %),
      hypophonia (n = 2, 6.6 %), and dysphonia (n = 2, 6.6 %). Four patients (13.2 %)
      had more complex presentations with different combinations of these patterns. No
      differences in gender, age at onset, and distribution of PMDs were observed
      between patients with and without PSVD. PSVDs are relatively frequent in patients
      with PMDs and are manifested by a wide variety of abnormal speech and voice
      phenomena, with stuttering being the most common presentation. Speech therapy and
      insight-oriented counseling may be helpful to some patients.

PMID- 26194200
TI  - Testing new treatments for paediatric epilepsies.

PMID- 26194201
TI  - Frequent misdiagnosis of adult polyglucosan body disease.
AB  - Adult polyglucosan body disease (APBD) is a rare glycogenosis manifesting
      progressive spastic paraparesis, sensorimotor polyneuropathy and neurogenic
      bladder. Misdiagnosis of APBD may lead to unnecessary investigations and to
      potentially harmful therapeutic interventions. To examine the frequency of
      misdiagnosis of APBD, we retrospectively reviewed the clinical data of 30
      patients diagnosed between 1991 and 2013. Diagnosis was based on the combination
      of typical clinical and imaging findings, reduced glycogen branching enzyme
      activity, and the presence of p.Y326S GBE1 mutation. Initial symptoms started in
      the 5th-6th decade with bladder dysfunction (47 %), gait problems (33 %) or both.
      Diagnosis of APBD was delayed by 6.8 (+/-4.8) years. Consistent signs at
      diagnosis were spasticity in the legs (93 %), decreased or absent ankle reflexes
      (100 %), bilateral extensor plantar response (100 %) and distal sensory deficit
      (80 %). Nerve conduction study showed invariable sensorimotor polyneuropathy, and
      MRI demonstrated cervical spinal cord atrophy (100 %) and leukoencephalopathy (97
      %). All 30 patients were initially misdiagnosed. Common misdiagnoses included
      cerebral small vessel disease (27 %), multiple sclerosis (17 %), amyotrophic
      lateral sclerosis (17 %) and peripheral neuropathies (20 %). Consequently, 27 %
      received inappropriate therapy. In addition, lower urinary tract symptoms in 60 %
      of men were attributed solely to prostatic disorders but did not respond to
      medical treatment or prostatectomy. These findings suggest that despite limited
      clinical variability, APBD is invariably misdiagnosed and patients are often
      mistreated. Physicians' unfamiliarity with the typical clinical and imaging
      features of APBD appears as the main reason for misdiagnosis.

PMID- 26194202
TI  - Cystathionine gamma-lyase regulates arteriogenesis through NO-dependent monocyte
      recruitment.
AB  - AIMS: Hydrogen sulfide (H2S) is a vasoactive gasotransmitter that is endogenously
      produced in the vasculature by the enzyme cystathionine gamma-lyase (CSE).
      However, the importance of CSE activity and local H2S generation for ischaemic
      vascular remodelling remains completely unknown. In this study, we examine the
      hypothesis that CSE critically regulates ischaemic vascular remodelling involving
      H2S-dependent mononuclear cell regulation of arteriogenesis. METHODS AND RESULTS:
      Arteriogenesis including mature vessel density, collateral formation, blood flow,
      and SPY angiographic blush rate were determined in wild-type (WT) and CSE
      knockout (KO) mice at different time points following femoral artery ligation
      (FAL). The role of endogenous H2S in regulation of IL-16 expression and
      subsequent recruitment of monocytes, and expression of VEGF and bFGF in ischaemic
      tissues, were determined along with endothelial progenitor cell (CD34/Flk1)
      formation and function. FAL of WT mice significantly increased CSE activity,
      expression and endogenous H2S generation in ischaemic tissues, and monocyte
      infiltration, which was absent in CSE-deficient mice. Treatment of CSE KO mice
      with the polysulfide donor diallyl trisulfide restored ischaemic vascular
      remodelling, monocyte infiltration, and cytokine expression. Importantly,
      exogenous H2S therapy restored nitric oxide (NO) bioavailability in CSE KO mice
      that was responsible for monocyte recruitment and arteriogenesis. CONCLUSION:
      Endogenous CSE/H2S regulates ischaemic vascular remodelling mediated during hind
      limb ischaemia through NO-dependent monocyte recruitment and cytokine induction
      revealing a previously unknown mechanism of arteriogenesis.

PMID- 26194203
TI  - Genome-Wide Association Study of Down Syndrome-Associated Atrioventricular Septal
      Defects.
AB  - The goal of this study was to identify the contribution of common genetic
      variants to Down syndrome-associated atrioventricular septal defect, a severe
      heart abnormality. Compared with the euploid population, infants with Down
      syndrome, or trisomy 21, have a 2000-fold increased risk of presenting with
      atrioventricular septal defects. The cause of this increased risk remains
      elusive. Here we present data from the largest heart study conducted to date on a
      trisomic background by using a carefully characterized collection of individuals
      from extreme ends of the phenotypic spectrum. We performed a genome-wide
      association study using logistic regression analysis on 452 individuals with Down
      syndrome, consisting of 210 cases with complete atrioventricular septal defects
      and 242 controls with structurally normal hearts. No individual variant achieved
      genome-wide significance. We identified four disomic regions (1p36.3, 5p15.31,
      8q22.3, and 17q22) and two trisomic regions on chromosome 21 (around PDXK and
      KCNJ6 genes) that merit further investigation in large replication studies. Our
      data show that a few common genetic variants of large effect size (odds ratio
      >2.0) do not account for the elevated risk of Down syndrome-associated
      atrioventricular septal defects. Instead, multiple variants of low-to-moderate
      effect sizes may contribute to this elevated risk, highlighting the complex
      genetic architecture of atrioventricular septal defects even in the highly
      susceptible Down syndrome population. 

PMID- 26194205
TI  - Addressing Health Literacy Challenges With a Cutting-Edge Infectious Disease
      Curriculum for the High School Biology Classroom.
AB  - This study reports the secondary analysis of evaluation data from an innovative
      high school biology curriculum focused on infectious disease (ID) to examine the
      health literacy implications of teaching claims evaluation, data interpretation,
      and risk assessment skills in the context of 21st-Century health science. The
      curriculum was implemented between 2010 and 2013 in Biology II classes held in
      four public high schools (three in Massachusetts and one in Ohio), plus a private
      school in Virginia. A quasi-experimental design was used in which student
      participants (n = 273) were compared to an age-matched, nonparticipant, peer
      group (N = 125). Participants in each school setting demonstrated increases in
      conceptual content knowledge (Cohen's d > 1.89) as well as in understanding how
      to apply scientific principles to health claims evaluation and risk assessment
      (Cohen's d > 1.76) and in self-efficacy toward learning about ID (Cohen's d >
      2.27). Participants also displayed enhanced communication about ID within their
      social networks relative to the comparison group (p < .05). The data show that
      integrating the claims evaluation, data interpretation, and risk assessment
      skills critical for 21st-century health literacy health into high school biology
      classrooms is effective at fostering both the skills and self-efficacy pertinent
      to health literacy learning in diverse populations. 

PMID- 26194204
TI  - Metabolic Impacts of Using Nitrogen and Copper-Regulated Promoters to Regulate
      Gene Expression in Neurospora crassa.
AB  - The filamentous fungus Neurospora crassa is a long-studied eukaryotic microbial
      system amenable to heterologous expression of native and foreign proteins.
      However, relatively few highly tunable promoters have been developed for this
      species. In this study, we compare the tcu-1 and nit-6 promoters for controlled
      expression of a GFP reporter gene in N. crassa. Although the copper-regulated tcu
      1 has been previously characterized, this is the first investigation exploring
      nitrogen-controlled nit-6 for expression of heterologous genes in N. crassa. We
      determined that fragments corresponding to 1.5-kb fragments upstream of the tcu-1
      and nit-6 open reading frames are needed for optimal repression and expression of
      GFP mRNA and protein. nit-6 was repressed using concentrations of glutamine from
      2 to 20 mM and induced in medium containing 0.5-20 mM nitrate as the nitrogen
      source. Highest levels of expression were achieved within 3 hr of induction for
      each promoter and GFP mRNA could not be detected within 1 hr after transfer to
      repressing conditions using the nit-6 promoter. We also performed metabolic
      profiling experiments using proton NMR to identify changes in metabolite levels
      under inducing and repressing conditions for each promoter. The results
      demonstrate that conditions used to regulate tcu-1 do not significantly change
      the primary metabolome and that the differences between inducing and repressing
      conditions for nit-6 can be accounted for by growth under nitrate or glutamine as
      a nitrogen source. Our findings demonstrate that nit-6 is a tunable promoter that
      joins tcu-1 as a choice for regulation of gene expression in N. crassa. 

PMID- 26194206
TI  - The Impact of Condom Use Negotiation Self-Efficacy and Partnership Patterns on
      Consistent Condom Use Among College-Educated Women.
AB  - This study sought to explore the impact of condom negotiation self-efficacy,
      interpersonal factors, and sensational factors on condom use behavior among a
      population of college-educated women with different patterns and types of sexual
      partner. We administered an online questionnaire capturing sexual behavior,
      partnership patterns, perceived benefits of and barriers to condom use, and
      condom use negotiation self-efficacy. A total of 433 women completed the online
      survey. Perceived sensual, erotic, and interpersonal benefits and barriers to
      condom use, along with negotiation self-efficacy, were found to be significantly
      associated with consistent condom use. When compared to respondents reporting
      only main partners, respondents reporting only casual partners were more likely
      to use condoms while respondents reporting both main and casual partners were
      least likely to use condoms. Previous negative experiences with condoms were
      significantly associated with decreased condom use, while history of sexually
      transmitted infection diagnosis was not consistently associated with condom use.
      This study supports the importance of negotiation self-efficacy in promoting
      condom use; however, building women's self-efficacy is not enough for effective
      condom use promotion among women. The impact of interpersonal, sensual and erotic
      factors, as well as the context of different partnership patterns, must be
      considered in future interventions. 

PMID- 26194207
TI  - Stentoplasty effectiveness and safety for the treatment of osteoporotic vertebral
      fractures: a systematic review.
AB  - To assess the effectiveness and safety of stentoplasty in people with
      osteoporotic vertebral body fractures. A systematic search of databases including
      MEDLINE, EMBASE and Cochrane library, between others, was conducted to June 9,
      2014. Clinical trials and observational studies that included alive adults with
      osteoporotic vertebral body fractures and the comparators were the intervention
      himself, vertebroplasty or balloon kyphoplasty were selected. Quality of evidence
      was graded according to the GRADE approach. Two review authors independently
      selected studies, assessed risk of bias and extracted data. Forty-two citations
      were identified during the search. After removing duplicates, five studies were
      included: two clinical trials and three observational studies. Stentoplasty,
      showed higher rate of adverse events related to material (P=0.043) and cuff
      pressure (P=0.014) in comparison to kyphoplasty. There was no difference between
      two procedures in terms of reduction of kyphosis, time of exposure to radiation
      or postoperative loss of cement. Stentoplasty in comparison to vertebroplasty,
      showed an improvement of restoration of vertebral height (P=0.042), kyphosis
      correction and volume of bone cement. No differences were found between two
      procedures in terms of loss of vertebral body volume. Based on observational
      studies, stentoplasty improved vertebral height, pain and functional disability
      at 6 and 12months follow-up, and corrected the angle vertebral fractures in
      patients with osteoporotic vertebral body. Stentoplasty was presented as a safe
      procedure in short-medium term, with a low complication rate, a reduced loss of
      cement and new vertebral body fractures lower rates. Stentoplasty improves
      vertebral height, reduces the pain and functional disability and correct the
      vertebral angle in patients with osteoporotic vertebral body fracture with
      minimum adverse events. Stentoplasty is comparable to kyphoplasty in terms of
      correction of kyphosis, time of exposure to radiation and cement postoperative
      loss, and comparable to vertebroplasty in terms of restoration of vertebral
      height correction and bone cement volume. LEVEL OF EVIDENCE: Level II systematic
      review.

PMID- 26194208
TI  - Evolution of adolescent idiopathic scoliosis: results of a multicenter study at
      20 years' follow-up.
AB  - INTRODUCTION: To date there is no consensus on therapeutic indications in
      adolescent idiopathic scoliosis (AIS) with curvature between 30 degrees  and 60
      degrees  at the end of growth. OBJECTIVE: The objective of this study was to
      assess outcome in patients with moderate AIS. MATERIAL AND METHODS: A multicenter
      retrospective study was conducted. Inclusion criteria were: Cobb angle, 30-60
      degrees  at end of growth; and follow-up > 20 years. The data collected were
      angular values in adolescence and at last follow-up, and quality of life scores
      at follow-up. RESULTS: A total of 258 patients were enrolled: 100 operated on in
      adolescence, 116 never operated on, and 42 operated on in adulthood. Mean follow
      up was 27.8 years. Cobb angle progression significantly differed between the 3
      groups: 3.2 degrees  versus 8.8 degrees  versus 23.6 degrees , respectively; P <
      0.001. In lumbar scoliosis, the risk of progression to >= 20 degrees  was
      significantly higher for initial Cobb angle > 35 degrees  (OR=4.278, P=0.002).
      There were no significant differences in quality of life scores. DISCUSSION:
      Patients operated on in adolescence showed little radiological progression,
      demonstrating the efficacy of surgical treatment for curvature greater than 50
      degrees . Curvature greater than 40 degrees  was progressive and may require
      surgery in adulthood. Lumbar scoliosis showed greater potential progression than
      thoracic scoliosis in adulthood, requiring fusion as of 35 degrees  angulation.
      LEVEL OF EVIDENCE: IV, retrospective study.

PMID- 26194209
TI  - Clinical and stereoradiographic analysis of adult spinal deformity with and
      without rotatory subluxation.
AB  - INTRODUCTION: In degenerative adult spinal deformity (ASD), sagittal malalignment
      and rotatory subluxation (RS) correlate with clinical symptomatology. RS is
      defined as axial rotation with lateral listhesis. Stereoradiography, recently
      developed for medical applications, provides full-body standing radiographs and
      3D reconstruction of the spine, with low radiation dose. HYPOTHESIS: 3D
      stereoradiography improves analysis of RS and of its relations with transverse
      plane and spinopelvic parameters and clinical impact. MATERIAL AND METHODS: One
      hundred and thirty adults with lumbar ASD and full-spine EOS(r) radiographs (EOS
      Imaging, Paris, France) were included. Spinopelvic sagittal parameters and
      lateral listhesis in the coronal plane were measured. The transverse plane study
      parameters were: apical axial vertebral rotation (apex AVR), axial intervertebral
      rotation (AIR) and torsion index (TI). Two groups were compared: with RS (lateral
      listhesis>5mm) and without RS (without lateral listhesis exceeding 5mm: non-RS).
      Correlations between radiologic and clinical data were assessed. RESULTS: RS
      patients were significantly older, with larger Cobb angle (37.4 degrees  vs. 26.6
      degrees , P=0.0001), more severe sagittal deformity, and greater apex AVR and TI
      (respectively: 22.9 degrees  vs. 11.3 degrees , P<0.001; and 41.0 degrees  vs.
      19.9 degrees , P<0.001). Ten percent of patients had AIR>10 degrees  without
      visible RS on 2D radiographs. RS patients reported significantly more frequent
      low back pain and radiculalgia. DISCUSSION: In this EOS(r) study, ASD patients
      with RS had greater coronal curvature and sagittal and transverse deformity, as
      well as greater pain. Further transverse plane analysis could allow earlier
      diagnosis and prognosis to guide management. LEVEL OF EVIDENCE: 4, retrospective
      study.

PMID- 26194211
TI  - First-line treatment in the management of advanced renal cell carcinoma:
      systematic review and network meta-analysis.
AB  - OBJECTIVES: To conduct a systematic review and network meta-analysis (NMA) to
      assess effectiveness of first-line treatments for advanced renal cell carcinoma
      (RCC). METHODS: Database searches were conducted to identify randomized
      controlled trials (RCTs) reporting results for eligible treatments. A fixed
      effect Bayesian NMA was conducted to assess the relative effectiveness of
      treatments, with progression-free survival (PFS) reported as hazard ratios (HRs)
      and 95% credible intervals (CrIs). RESULTS: Eleven unique RCTs were suitable for
      inclusion in the NMA. In the base case, in terms of PFS, sunitinib was superior
      compared with bevacizumab + IFN-alpha (HR = 0.79, 95% CrI: 0.64 - 0.96),
      everolimus (HR = 0.70, 95% CrI: 0.56 - 0.87), sorafenib (HR = 0.56, 95% CrI: 0.40
      - 0.77) and temsirolimus + bevacizumab (HR = 0.74, 95% CrI: 0.56 - 0.96).
      Although, the point values for the mean and median HRs were < 1.0, there was no
      significant difference in PFS between sunitinib and axitinib, pazopanib or
      tivozanib. Although sensitivity analyses impacted the results of the NMA, no
      treatment was significantly more efficacious than sunitinib. CONCLUSION: Results
      from this analysis suggest that there is no treatment superior to the current
      benchmark treatment, sunitinib, in the management of advanced RCC in the first
      line setting.

PMID- 26194210
TI  - Conversion paralysis after cervical spine arthroplasty: a case report and
      literature review.
AB  - We report a case of conversion paralysis after cervical spine arthroplasty
      performed in a 45-year-old woman to treat cervico-brachial neuralgia due to a
      left-sided C6-C7 disc herniation. Upon awakening from the anaesthesia, she had
      left hemiplegia sparing the face, with normal sensory function. Magnetic
      resonance imaging (MRI) of the brain ruled out a stroke. MRI of the spinal cord
      showed artefacts from the cobalt-chrome prosthesis that precluded confident
      elimination of mechanical spinal cord compression. Surgery performed on the same
      day to substitute a cage for the prosthesis ruled out spinal cord compression,
      while eliminating the source of MRI artefacts. Findings were normal from follow
      up MRI scans 1 and 15days later, as well as from neurophysiological testing
      (electromyogram and motor evoked potentials). The deficit resolved fully within
      the next 4days. A psychological assessment revealed emotional distress related to
      an ongoing divorce. The most likely diagnosis was conversion paralysis. Surgeons
      should be aware that conversion disorder might develop after a procedure on the
      spine, although the risk of litigation requires re-operation. Familiarity with
      specific MRI sequences that minimise artefacts can be valuable. A preoperative
      psychological assessment might improve the detection of patients at high risk for
      conversion disorder.

PMID- 26194212
TI  - Pharmacotherapy options to treat asthma during pregnancy.
AB  - INTRODUCTION: Pregnancy may be complicated by new onset or pre-existing asthma.
      This article reviews the recognition and management of asthma during pregnancy,
      paying close attention to the general principles of asthma medication use during
      pregnancy. Asthma is one of the most common potentially serious medical problems
      to complicate pregnancy, and asthma may adversely affect both maternal quality of
      life and perinatal outcomes. Therefore, optimal management of asthma during
      pregnancy is important for both mother and baby. This article reviews asthma
      pharmacotherapy during pregnancy, with an emphasis on gestational safety of
      commonly used medications. AREAS COVERED: In this review of asthma
      pharmacotherapy during pregnancy, the most pertinent recent publications are
      reported. Electronic databases such as PubMed were searched for terms pregnan* or
      perinat* or obstet* and asthma or wheeze and treatment. EXPERT OPINION: Although
      retrospective data have been reassuring, since pregnant women are generally
      excluded from clinical trials, there is a lack of adequate safety information for
      most medications taken during pregnancy. One of the most important needs for the
      future is the availability of further safety information for asthma medications
      used during pregnancy that can also account for asthma control.

PMID- 26194214
TI  - Ethinyl estradiol and levonorgestrel in a transdermal contraceptive delivery
      system.
AB  - INTRODUCTION: The new transdermal contraceptive delivery system (TCDS) developed
      by Agile Therapeutics containing ethinyl estradiol and levonorgestrel (EE/LNG) is
      a reversible contraceptive method that maintains stable serum levels of both
      estrogen and progestin, and has efficacy similar to that of combination oral
      contraceptives (COC). AREAS COVERED: We provided information of this new TCDS
      compared with the only TCDS available on the market that contains EE and
      norelgestromin, and has a higher EE exposure than a COC with 35 ug of EE
      potentially increasing the risk of venous thromboembolism. The article will
      summarize finding from clinical studies Phase I, II and III of EE/LNG TCDS.
      EXPERT OPINION: The development of the lower dose EE/LNG TCDS has demonstrated
      less EE exposure. The serum levels of EE and LNG were stable and comparable
      between various application sites and daily life conditions. Moreover, the EE/LNG
      TCDS showed comparable efficacy among obese and non-obese users. However, the
      Pearl index of this EE/LNG TCDS is questionable and the problem of compliance is
      a potential confounder of the results. The current Phase III efficacy study will
      contribute to a further evaluation of compliance and efficacy and will be
      completed in 2016.

PMID- 26194216
TI  - Carcass Composition and Cuts of Bulls and Steers Fed with Three Concentrate
      Levels in the Diets.
AB  - In this paper, weight, carcass dressing, weights of the primary cuts, weights of
      the physical components of the primary cuts, and weights of the main commercial
      cuts of 66 Puruna animals, of which 33 were bulls and 33 were steers were
      evaluated. These animals, with an average age of 19 months at the beginning of
      the experiment, were finished in a feedlot system during 116 days, and were fed
      with diets containing three levels of concentrate (0.8%, 1.1%, and 1.4% of body
      weight). The concentrate was formulated with 25% soybean meal, 73% ground corn
      grain, 1% of a mineral mix, and 1% of limestone. The interaction between sexual
      groups and the concentrate level was not significant for any of the variables.
      Likewise, no effect of the concentrate level was detected on the same variable
      traits. The bulls demonstrated higher hot carcass weights (265.1 vs 221.7 kg) and
      a higher proportion of forequarter (38.4% vs 36.1%) however the steers presented
      with higher proportions of side (19.7% vs 18.5%) and hindquarter (44.2% vs
      43.1%). The bulls produced higher yields of muscle in the three primary cuts,
      there by resulting in higher yields of edible portions of the carcass. The bulls
      also produced higher weights of tenderloin, knuckle, topside, flat, eye round,
      rump, and rump cover. The finishing of young bulls in feedlot is to be
      recommended, since the animals produce carcasses with higher amounts of edible
      meat and higher yields of commercial cuts, thus allowing for a better price for
      the carcass. Low concentrate level could be used due to the lower cost of
      production for farmers. 

PMID- 26194213
TI  - A re-evaluation of the role of inhaled corticosteroids in the management of
      patients with chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Inhaled corticosteroids (ICS) (in fixed combinations with long
      acting beta2-agonists [LABAs]) are frequently prescribed for patients with
      chronic obstructive pulmonary disease (COPD), outside their labeled indications
      and recommended treatment strategies and guidelines, despite having the potential
      to cause significant side effects. AREAS COVERED: Although the existence of
      asthma in patients with asthma-COPD overlap syndrome (ACOS) clearly supports the
      use of anti-inflammatory treatment (typically an ICS/LABA combination, as ICS
      monotherapy is usually not indicated for COPD), the current level of ICS/LABA use
      is not consistent with the prevalence of ACOS in the COPD population. Data have
      recently become available showing the comparative efficacy of fixed
      bronchodilator combinations (long-acting muscarinic antagonist [LAMA]/LABA with
      ICS/LABA combinations). Additionally, new information has emerged on ICS
      withdrawal without increased risk of exacerbations, under cover of effective
      bronchodilation. EXPERT OPINION: For patients with COPD who do not have ACOS, a
      LAMA/LABA combination may be an appropriate starting therapy, apart from those
      with mild disease who can be managed with a single long-acting bronchodilator.
      Patients who remain symptomatic or present with exacerbations despite effectively
      delivered LAMA/LABA treatment may require additional drug therapy, such as ICS or
      phosphodiesterase-4 inhibitors. When prescribing an ICS/LABA, the risk:benefit
      ratio should be considered in individual patients.

PMID- 26194217
TI  - Genetic Analysis of Milk Yield in First-Lactation Holstein Friesian in Ethiopia:
      A Lactation Average vs Random Regression Test-Day Model Analysis.
AB  - The development of effective genetic evaluations and selection of sires requires
      accurate estimates of genetic parameters for all economically important traits in
      the breeding goal. The main objective of this study was to assess the relative
      performance of the traditional lactation average model (LAM) against the random
      regression test-day model (RRM) in the estimation of genetic parameters and
      prediction of breeding values for Holstein Friesian herds in Ethiopia. The data
      used consisted of 6,500 test-day (TD) records from 800 first-lactation Holstein
      Friesian cows that calved between 1997 and 2013. Co-variance components were
      estimated using the average information restricted maximum likelihood method
      under single trait animal model. The estimate of heritability for first-lactation
      milk yield was 0.30 from LAM whilst estimates from the RRM model ranged from 0.17
      to 0.29 for the different stages of lactation. Genetic correlations between
      different TDs in first-lactation Holstein Friesian ranged from 0.37 to 0.99. The
      observed genetic correlation was less than unity between milk yields at different
      TDs, which indicated that the assumption of LAM may not be optimal for accurate
      evaluation of the genetic merit of animals. A close look at estimated breeding
      values from both models showed that RRM had higher standard deviation compared to
      LAM indicating that the TD model makes efficient utilization of TD information.
      Correlations of breeding values between models ranged from 0.90 to 0.96 for
      different group of sires and cows and marked re-rankings were observed in top
      sires and cows in moving from the traditional LAM to RRM evaluations. 

PMID- 26194218
TI  - Estimation of Growth Curves and Suitable Slaughter Weight of the Liangshan Pig.
AB  - The Liangshan pig is a traditional Chinese small-sized breed; it has a relatively
      long feeding period and low meat production ability but superior meat quality.
      This study utilized three non-linear growth models (Von Bertalanffy, Gompertz,
      and logistic) to fit the growth curve of Liangshan pigs from an unselected,
      random-bred pig population and estimate the pigs most suitable slaughter weight.
      The growth development data at 20 time points of 275 Liangshan pigs (from birth
      to 250 d) were collected. To analyze the relative gene expression related to
      development, seven slaughter weight phases (50, 58, 66, 74, 82, 90, and 98 kg)
      (20 pigs per phase) were examined. We found that the Liangshan pig growth curve
      fit the typical S-curve well and that their growth turning point was 193.4 days
      at a weight of 62.5 kg, according to the best fit Von Bertalanffy model based on
      the goodness of fit criteria. Furthermore, we estimated that the most suitable
      slaughter weight was 62.5 to 74.9 kg based on the growth curve and the relative
      expression levels of growth-related genes. 

PMID- 26194219
TI  - Effect of Dietary Protein Levels on Composition of Odorous Compounds and
      Bacterial Ecology in Pig Manure.
AB  - This study was performed to investigate the effect of different levels of dietary
      crude protein (CP) on composition of odorous compounds and bacterial communities
      in pig manure. A total of 48 male pigs (average initial body weight 45 kg) fed
      diets containing three levels of dietary CP (20%, 17.5%, and 15%) and their
      slurry samples were collected from the pits under the floor every week for one
      month. Changes in composition of odorous compounds and bacterial communities were
      analyzed by gas chromatography and 454 FLX titanium pyrosequencing systems,
      respectively. Levels of phenols, indoles, short chain fatty acid and branched
      chain fatty acid were lowest (p<0.05) in CP 15% group among three CP levels.
      Relative abundance of Bacteroidetes phylum and bacterial genera including
      Leuconostoc, Bacillus, Atopostipes, Peptonphilus, Ruminococcaceae_uc,
      Bacteroides, and Pseudomonas was lower (p<0.05) in CP 15% than in CP 20% group.
      There was a positive correlation (p<0.05) between odorous compounds and bacterial
      genera: phenol, indole, iso-butyric acid, and iso-valeric acid with Atopostipes,
      p-cresol and skatole with Bacteroides, acetic acid and butyric acid with
      AM982595_g of Porphyromonadaceae family, and propionic acid with Tissierella.
      Taken together, administration of 15% CP showed less production of odorous
      compounds than 20% CP group and this result might be associated with the changes
      in bacterial communities especially whose roles in protein metabolism. 

PMID- 26194220
TI  - Effects of Nitrate Addition on Rumen Fermentation, Bacterial Biodiversity and
      Abundance.
AB  - This study examined changes of rumen fermentation, ruminal bacteria biodiversity
      and abundance caused by nitrate addition with Ion Torrent sequencing and real
      time polymerase chain reaction. Three rumen-fistulated steers were fed diets
      supplemented with 0%, 1%, and 2% nitrate (dry matter %) in succession. Nitrate
      supplementation linearly increased total volatile fatty acids and acetate
      concentration obviously (p = 0.02; p = 0.02; p<0.01), butyrate and isovalerate
      concentration numerically (p = 0.07). The alpha (p>0.05) and beta biodiversity of
      ruminal bacteria were not affected by nitrate. Nitrate increased typical
      efficient cellulolytic bacteria species (Ruminococcus flavefaciens, Ruminococcus
      ablus, and Fibrobacter succinogenes) (p<0.01; p = 0.06; p = 0.02). Ruminobactr,
      Sphaerochaeta, CF231, and BF311 genus were increased by 1% nitrate. Campylobacter
      fetus, Selenomonas ruminantium, and Mannheimia succiniciproducens were core
      nitrate reducing bacteria in steers and their abundance increased linearly along
      with nitrate addition level (p<0.01; p = 0.02; p = 0.04). Potential nitrate
      reducers in the rumen, Campylobacter genus and Cyanobacteria phyla were
      significantly increased by nitrate (p<0.01; p = 0.01). To the best of our
      knowledge, this was the first detailed view of changes in ruminal microbiota by
      nitrate. This finding would provide useful information on nitrate utilization and
      nitrate reducer exploration in the rumen. 

PMID- 26194221
TI  - Effects of Dietary L-carnosine and Alpha-lipoic Acid on Growth Performance, Blood
      Thyroid Hormones and Lipid Profiles in Finishing Pigs.
AB  - The present study was conducted to determine the effects of L-carnosine (LC)
      and/or alpha-lipoic acid (ALA) supplementation on growth performance, blood
      thyroid hormones and lipid profiles in finishing pigs. A total of 40
      (Landrace*Yorkshire) pigs with an initial body weight of 57.93+/-3.14 kg were
      randomly allocated to 4 experimental diets using a 2*2 factorial arrangement with
      2 LC supplemental levels (0 or 0.1%) and 2 ALA supplemental levels (0 or 0.03%)
      in basal diets. The results showed that pigs fed LC-supplemented diets increased
      final live weight, average daily gain, and average daily feed intake compared to
      those of pigs fed without LC-supplemented diets (p<0.05). Dietary supplementation
      with ALA did not affect the growth performance and carcass traits of pigs
      (p>0.05). Additionally, LC supplementation increased serum triiodothyronine,
      thyroxine levels, and ALA supplementation increased serum triiodothyronine levels
      (p<0.05). Serum total cholesterol and triglycerides levels were significantly
      decreased in LC and ALA supplemented groups, respectively (p<0.05). Moreover,
      serum low density lipoprotein cholesterol levels were lower in the ALA
      supplemented groups than those of pigs fed without ALA-supplemented diets
      (p<0.05). However, no significant LC*ALA interaction effect on growth
      performance, blood thyroid hormones and lipid profiles was found. This study
      suggested that dietary supplementation of LC resulted in better growth
      performance compared to that of ALA supplementation. L-carnosine and/or ALA
      supplementation positively modified blood lipid profiles, which may have the
      potential to prevent cardiovascular diseases. 

PMID- 26194222
TI  - Genetic Association of the Porcine C9 Complement Component with Hemolytic
      Complement Activity.
AB  - The complement system is a part of the natural immune regulation mechanism
      against invading pathogens. Complement activation from three different pathways
      (classical, lectin, and alternative) leads to the formation of C5-convertase, an
      enzyme for cleavage of C5 into C5a and C5b, followed by C6, C7, C8, and C9 in
      membrane attack complex. The C9 is the last complement component of the terminal
      lytic pathway, which plays an important role in lysis of the target cells
      depending on its self-polymerization to form transmembrane channels. To address
      the association of C9 with traits related to disease resistance, the complete
      porcine C9 cDNA was comparatively sequenced to detect single nucleotide
      polymorphisms (SNPs) in pigs of the breeds Hampshire (HS), Duroc (DU), Berlin
      miniature pig (BMP), German Landrace (LR), Pietrain (PIE), and Muong Khuong
      (Vietnamese potbelly pig). Genotyping was performed in 417 F2 animals of a
      resource population (DUMI: DU*BMP) that were vaccinated with Mycoplasma
      hyopneumoniae, Aujeszky diseases virus and porcine respiratory and reproductive
      syndrome virus at 6, 14 and 16 weeks of age, respectively. Two SNPs were detected
      within the third exon. One of them has an amino acid substitution. The European
      porcine breeds (LR and PIE) show higher allele frequency of these SNPs than
      Vietnamese porcine breed (MK). Association of the substitution SNP with hemolytic
      complement activity indicated statistically significant differences between
      genotypes in the classical pathway but not in the alternative pathway. The
      interactions between eight time points of measurement of complement activity
      before and after vaccinations and genotypes were significantly different. The
      difference in hemolytic complement activity in the both pathways depends on
      genotype, kind of vaccine, age and the interaction to the other complement
      components. These results promote the porcine C9 (pC9) as a candidate gene to
      improve general animal health in the future. 

PMID- 26194223
TI  - Genetic Relationship of Productive Life, Production and Type Traits of Korean
      Holsteins at Early Lactations.
AB  - The present study was performed to study the genetic relationship of productive
      life with production and type traits of Korean Holsteins at first three
      lactations. The data for the analysis from 56,054, 28,997, and 11,816 animals of
      first, second and third parity cows which were born from 2006 to 2011 were
      collected by Dairy Cattle Improvement Center, National Agricultural Co-operative
      Federation. Milk, protein and fat yields adjusted for 305 days and average
      somatic cell score considered as production traits and analyzed type traits were
      stature, strength, body depth, dairy form, rump angle, rump width, rear leg side
      view, foot angle, front attachment placement, rear attachment height, rear
      attachment width, udder cleft, udder depth, front teat placement and front teat
      length. A multi trait genetic analysis was performed using Wombat program with
      restricted maximum likelihood animal model composed of fixed effect of birth
      year, farm and the random effect of animal and random residual effect according
      to the traits. Heritability estimates of productive life were between 0.06 and
      0.13. Genetic and phenotypic correlations between production and productive life
      traits ranged from 0.35 to 0.04 for milk, 0.16 to 0.05 for protein and 0.18 to
      0.02 f 15-0034 (2nd) 150520 or fat. Somatic cells score showed a negative genetic
      and phenotypic correlation with productive life and also udder type traits,
      indicating that the selection for higher udder traits will likely to improve
      resistance to mastitis and persistence in the herd. Among all dairy form type
      traits, udder characters such as udder cleft showed a significant relationship
      with productive life. However, a specific change of heritabilities or
      correlations were not observed with the change of parity. Moreover, further
      studies are needed to further confirm the significance of the above traits and
      the effect of parity on above relationships in order to minimize both voluntary
      and involuntary culling rates while improving herd health and maintaining high
      yielding dairy cows. 

PMID- 26194224
TI  - Responses to Starch Infusion on Milk Synthesis in Low Yield Lactating Dairy Cows.
AB  - The effect of starch infusion on production, metabolic parameters and relative
      mRNA abundance was investigated in low yield lactating cows from 86 days in milk.
      Six Holstein cows fitted with permanent ruminal cannulas were arranged into one
      of two complete 3*3 Latin squares and infused with a starch solution containing
      800 grams starch for 16 days. The three treatments were: i) ruminal and abomasal
      infusion with water (Control); ii) ruminal infusion with cornstarch solution and
      abomasal infusion with water (Rumen); iii) ruminal infusion with water and
      abomasal infusion with cornstarch solution (Abomasum). There were no significant
      differences (p>0.05) among the three treatments with low yield lactating cows in
      feed and energy intake, milk yield and composition, plasma metabolism, or even on
      gene expression. However, cows receiving starch through rumen performed better
      than directly through the abomasum during the glucose tolerance test procedure
      with a higher area under the curve (AUC; p = 0.08) and shorter half-time (t(1/2);
      p = 0.11) of plasma insulin, therefore, it increased glucose disposal, which
      stated a lipid anabolism other than mobilization after energy supplementation. In
      conclusion, extra starch infusion at concentration of 800 g/d did not enhance
      energy supplies to the mammary gland and improve the lactating performance in low
      yield lactating cows. 

PMID- 26194225
TI  - Influence of Feeding Enzymatically Hydrolyzed Yeast Cell Wall on Growth
      Performance and Digestive Function of Feedlot Cattle during Periods of Elevated
      Ambient Temperature.
AB  - In experiment 1, eighty crossbred steers (239+/-15 kg) were used in a 229-d
      experiment to evaluate the effects of increasing levels of enzymatically
      hydrolyzed yeast (EHY) cell wall in diets on growth performance feedlot cattle
      during periods of elevated ambient temperature. Treatments consisted of steam
      flaked corn-based diets supplemented to provide 0, 1, 2, or 3 g EHY/hd/d. There
      were no effects on growth performance during the initial 139-d period. However,
      from d 139 to harvest, when 24-h temperature humidity index averaged 80, EHY
      increased dry matter intake (DMI) (linear effect, p<0.01) and average daily gain
      (ADG) (linear effect, p = 0.01). There were no treatment effects (p>0.10) on
      carcass characteristics. In experiment 2, four Holstein steers (292+/-5 kg) with
      cannulas in the rumen and proximal duodenum were used in a 4*4 Latin Square
      design experiment to evaluate treatments effects on characteristics of ruminal
      and total tract digestion in steers. There were no treatment effects (p>0.10) on
      ruminal pH, total volatile fatty acid, molar proportions of acetate, butyrate, or
      estimated methane production. Supplemental EHY decreased ruminal molar proportion
      of acetate (p = 0.08), increased molar proportion of propionate (p = 0.09), and
      decreased acetate:propionate molar ratio (p = 0.07) and estimated ruminal methane
      production (p = 0.09). It is concluded that supplemental EHY may enhance DMI and
      ADG of feedlot steers during periods of high ambient temperature. Supplemental
      EHY may also enhance ruminal fiber digestion and decrease ruminal
      acetate:propionate molar ratios in feedlot steers fed steam-flaked corn-based
      finishing diets. 

PMID- 26194226
TI  - Apparent or Standardized Ileal Digestibility of Amino Acids of Diets Containing
      Different Protein Feedstuffs Fed at Two Crude Protein Levels for Growing Pigs.
AB  - The current study determined the apparent or standardized ileal digestibility of
      amino acids (AID or SID of AA) in growing pigs fed diets containing three protein
      feedstuffs with different fiber characteristics at two dietary crude protein (CP)
      levels. Twenty boars (Yorkshire*Landrace) with average initial body weight of 35
      (+/-2.6) kg were fitted with a simple T-cannula at the distal ileum. These pigs
      were offered six diets containing soybean meal (SBM), canola meal (CM) or corn
      distillers dried grains with solubles (corn-DDGS) that were either adequate (19%)
      or marginal (15%) in CP using a triplicated 6*2 Youden Square Design. Except for
      Met, Trp, Cys, and Pro, AID of AA was greater (p<0.05) in the SBM diet compared
      with the CM diet. Apparent ileal digestibility for Gly and Asp was greater
      (p<0.05) in the SBM diet compared with the corn-DDGS diet. The AID of Ile, Leu,
      Phe, Val, Ala, Tyr, and Asp was greater (p<0.05) in the corn-DDGS diet compared
      with the CM diet. Standardized ileal digestibility of AA was greater (p<0.05) in
      the SBM diet compared with the CM diet for all AA except Trp and Pro. The SID of
      Ile, Leu, Val, Ala, Tyr, and Asp was greater (p<0.05) in the corn-DDGS diet
      compared with the CM diet. It was concluded that protein feedstuff affects ileal
      AA digestibility and is closely related to dietary fiber characteristics, and a 4
      percentage unit reduction in dietary CP had no effect on ileal AA digestibility
      in growing pigs. 

PMID- 26194227
TI  - Energy Value of Cassava Products in Broiler Chicken Diets with or without Enzyme
      Supplementation.
AB  - This study investigated the metabolizable energy (ME) intake, net energy of
      production (NEp), heat production (HP), efficiencies of ME use for energy, lipid
      and protein retention as well as the performance of broiler chickens fed diets
      based on cassava chips or pellets with or without supplementation with an enzyme
      product containing xylanase, amylase, protease and phytase. The two products,
      cassava chips and pellets, were analysed for nutrient composition prior to feed
      formulation. The cassava chips and pellets contained 2.2% and 2.1% crude protein;
      1.2% and 1.5% crude fat; and 75.1% and 67.8% starch, respectively. Lysine and
      methionine were 0.077%, 0.075%, and 0.017%, 0.020% protein material,
      respectively, while calculated ME was 12.6 and 11.7 MJ/kg, respectively. Feed
      intake to day 21 was lower (p<0.01) on the diet containing cassava chips compared
      to diets with cassava pellets. Enzyme supplementation increased (p<0.01) feed
      intake on all diets. Live weight at day 21 was significantly (p<0.01) reduced on
      the diet based on cassava chips compared to pellets, but an improvement (p<0.01)
      was noticed with the enzyme supplementation. Metabolizable energy intake was
      reduced (p<0.01) by both cassava chips and pellets, but was increased (p<0.01) on
      all diets by enzyme supplementation. The NEp was higher (p<0.01) in the maize
      based diets than the diets containing cassava. Enzyme supplementation improved
      (p<0.01) NEp in all the diets. Heat production was highest (p<0.01) on diets
      containing cassava pellets than on cassava chips. It is possible to use cassava
      pellets in diets for broiler chickens at a level close to 50% of the diet to
      reduce cost of production, and the nutritive value of such diets can be improved
      through supplementation of enzyme products containing carbohydrases, protease,
      and phytase. 

PMID- 26194228
TI  - Study on the Changes in Enzyme and Insulin-like Growth Factor-1 Concentrations in
      Blood Serum and Growth Characteristics of Velvet Antler during the Antler Growth
      Period in Sika Deer (Cervus nippon).
AB  - This study was conducted to investigate changes in blood enzyme parameters and to
      evaluate the relationship between insulin-like growth factor-1 (IGF-1), antler
      growth and body weight during the antler growth of sika deer (Cervus nippon).
      Serum enzyme activity and IGF-1 concentrations were measured in blood samples
      collected from the jugular and femoral veins at regular intervals during the
      antler growth period. Blood samples were taken in the morning from fasted stags
      (n = 12) which were healthy and showed no clinical signs of disease. Alfalfa was
      available ad libitum and concentrates were given at 1% of body weight to all
      stags. The experimental diet was provided at 9 am with water available at all
      times. There were no significant differences in alkaline phosphatase, aspartate
      aminotransferase, and alanine aminotransferase during antler growth, but alkaline
      phosphatase concentrations increased with antler growth progression, and the
      highest alkaline phosphatase concentration was obtained 55 days after antler
      casting. Serum IGF-1 concentrations measured from blood samples taken from the
      jugular vein during antler growth, determined that levels of IGF-1 was associated
      with body weight and antler growth patterns. Serum IGF-1 concentrations were
      higher at the antler cutting date than other sampling dates. Antler length
      increased significantly during antler growth (p<0.001), and there was a similar
      trend to between right and left beams. Body weight increased with antler growth
      but was not significant. Consequently it appeared that serum alkaline phosphatase
      concentration was related to antler growth and both antler growth and body weight
      were associated positively with IGF-1 concentrations during antler growth. 

PMID- 26194229
TI  - Stories and Challenges of Genome Wide Association Studies in Livestock - A
      Review.
AB  - Undoubtedly livestock is one of the major contributors to the economy of any
      country. The economic value of livestock includes meat, dairy products, fiber,
      fertilizer etc. Understanding and identifying the associations of quantitative
      trait loci (QTL) with the economically important traits is believed to
      substantially benefit the livestock industry. The past two decades have seen a
      flurry of interest in mapping the QTL associated with traits of economic
      importance on the genome. With the availability of single nucleotide polymorphism
      chip of various densities it is possible to identify regions, QTL and genes on
      the genome that explain the association and its effect on the phenotype under
      consideration. Remarkable advancement has been seen in genome wide association
      studies (GWAS) since its inception till the present day. In this review we
      describe the progress and challenges of GWAS in various livestock species. 

PMID- 26194230
TI  - Validation of Prediction Equations of Energy Values of a Single Ingredient or
      Their Combinations in Male Broilers.
AB  - A set of prediction equations to estimate the nitrogen-corrected apparent
      metabolizable energy (AMEn) of individual ingredients and diets used in the
      poultry feed industry was evaluated. The AMEn values of three energy ingredients
      (maize, sorghum and defatted maize germ meal), four protein ingredients (soybean
      meal, maize gluten meal 60% crude protein, integral micronized soy and roasted
      whole soybean) and four diets (three containing four feedstuffs, complex diets,
      and one containing only corn-soybean meal, basal diet) were determined using a
      metabolism assay with male broilers from 1 to 7, 8 to 21, 22 to 35, and 36 to 42
      days old. These values were compared to the AMEn values presented in the tables
      of energy composition or estimated by equation predictions based on chemical
      composition data of feedstuffs. In general, the equation predictions more
      precisely estimated the AMEn of feedstuffs when compared to the tables of energy
      composition. The equation AMEn (dry matter [DM] basis) = 4,164.187+51.006 ether
      extract (% in DM basis)-197.663 ash-35.689 crude fiber (% in DM basis)-20.593
      neutral detergent fiber (% in DM basis) (R(2) = 0.75) was the most applicable for
      the prediction of the energy values of feedstuffs and diets used in the poultry
      feed industry. 

PMID- 26194231
TI  - Circadian and ultradian rhythms of clock gene expression in the suprachiasmatic
      nucleus of freely moving mice.
AB  - In mammals, the temporal order of physiology and behavior is primarily regulated
      by the circadian pacemaker located in the hypothalamic suprachiasmatic nucleus
      (SCN). Rhythms are generated in cells by an auto-regulatory
      transcription/translation feedback loop, composed of several clock genes and
      their protein products. Taking advantage of bioluminescence reporters, we have
      succeeded in continuously monitoring the expression of clock gene reporters Per1
      luc, PER2::LUC and Bmal1-ELuc in the SCN of freely moving mice for up to 3 weeks
      in constant darkness. Bioluminescence emitted from the SCN was collected with an
      implanted plastic optical fiber which was connected to a cooled photomultiplier
      tube. We found robust circadian rhythms in the clock gene expression, the phase
      relation of which were the same as those observed ex vivo. The circadian rhythms
      were superimposed by episodic bursts which had ultradian periods of approximately
      3.0 h. Episodic bursts often accompanied activity bouts, but stoichiometric as
      well as temporal analyses revealed no causality between them. Clock gene
      expression in the SCN in vivo is regulated by the circadian pacemaker and
      ultradian rhythms of unknown origin.

PMID- 26194232
TI  - Impact of short-term climate variation and hydrology change on thermal structure
      and water quality of a canyon-shaped, stratified reservoir.
AB  - Climate variation can have obvious effects on hydrologic conditions, which in
      turn can have direct consequences for the thermal regime and quality of water for
      human use. In this research, weekly surveys were conducted from 2011 to 2013 to
      investigate how changes of climate and hydrology affect the thermal regime and
      water quality at the Heihe Reservoir. Our results show that the hydrology change
      during the flooding season can both increase the oxygen concentration and
      accelerate the consumption of dissolved oxygen. Continuous heavy rainfall events
      occurred in September 2011 caused the mixing of the entire reservoir, which led
      to an increase in dissolved oxygen at the bottom until the next year. Significant
      turbid density flow was observed following the extreme rainfall events in 2012
      which leading to a rapid increase in turbidity at the bottom (up to 3000 NTU).
      Though the dissolved oxygen at the bottom increased from 0 to 9.02 mg/L after the
      rainfall event, it became anoxic within 20 days due to the increase of water
      oxygen demand caused by the suspended matter brought by the storm runoff. The
      release of compounds from the sediments was more serious during the anaerobic
      period after the rainfall events and the concentration of total iron, total
      phosphorus, and total manganese at the bottom reached 1.778, 0.102, and 0.125
      mg/L. The improved water-lifting aerators kept on running after the storm runoff
      occurred in 2013 to avoid the deterioration of water quality during anaerobic
      conditions and ensured the good water quality during the mixing period. Our
      results suggest preventive and remediation actions that are necessary to improve
      water quality and status.

PMID- 26194233
TI  - Enhanced photodegradation of pentachlorophenol by single and mixed nonionic and
      anionic surfactants using graphene-TiO2 as catalyst.
AB  - The photodegradation of pentachlorophenol (PCP) in a surfactant-containing
      (single and mixed) complex system using graphene-TiO2 (GT) as catalyst was
      investigated. The objective was to better understand the behavior of surfactants
      in a GT catalysis system for its possible use in remediation technology of soil
      contaminated by hydrophobic organic compounds (HOCs). In a single-surfactant
      system, surfactant molecules aggregated on GT via hydrogen bonding and
      electrostatic force; nonideal mixing between nonionic and anionic surfactants
      rendered GT surface with mixed admicelles in a mixed surfactant system. Both
      effects helped incorporating PCP molecules into surfactant aggregates on catalyst
      surface. Hence, the targeted pollutants were rendered easily available to photo
      yielded oxidative radicals, and photodegradation efficiency was significantly
      enhanced. Finally, real soil washing-photocatalysis trials proved that anionic
      nonionic mixed surfactant soil washing coupled with graphene-TiO2 photocatalysis
      can be one promising technology for HOC-polluted soil remediation. 

PMID- 26194235
TI  - Ecological significance of Synergistetes in the biological treatment of tuna
      cooking wastewater by an anaerobic sequencing batch reactor.
AB  - Lab-scale 2L-anaerobic sequencing batch reactor was operated under mesothermic
      conditions. The degradation of protein-rich organic matter was determined by
      chemical oxygen demand, biogas production, and protein-removal activity over the
      operation. The structure of the microbial community was determined by qPCR and
      next-generation sequencing on 16S rRNA genes. At the steady state, a very
      efficient removal of protein (92%) was observed. Our results demonstrate a
      decrease of archaeal and bacterial abundance over time. Members of the phylum
      Synergistetes, with a peculiar emphasis for those pertaining to families
      Dethiosulfovibrionaceae and Aminiphilaceae, are of major ecological significance
      regarding the treatment of this industrial wastewater. The prominent role to be
      played by members of the phylum Synergistetes regarding protein and/or amino acid
      degradation is discussed.

PMID- 26194236
TI  - Oxidative stress tolerance in intertidal red seaweed Hypnea musciformis (Wulfen)
      in relation to environmental components.
AB  - Oxidative stress parameters in relation to temperature and other factors have
      been analysed in Hypnea musciformis, the red seaweed from Anjuna beach, Goa, with
      an aim to understand its susceptibility to the changing seasons. The results
      indicate that elevated temperature, sunshine and dessication during peak summer
      in May enhanced the activity of lipid peroxide, hydrogen peroxide and
      antioxidants such as catalase, glutathione and ascorbic acid. Statistical tests
      using multivariate analysis of variance and correlation analysis showed that
      oxidative stress and antioxidants maintain significant relation with temperature,
      salinity, sunshine and pH at an individual or interactive level. The dissolved
      nitrates, phosphates and biological oxygen demand in ambient waters and the trace
      metals in seaweeds maintained sufficiently low values to provide any indication
      that could exert contaminant oxidative stress responses. The present field
      studies suggest that elevated antioxidant content in H. musciformis offer
      sufficient relief to sustain against harsh environmental stresses for its
      colonization in the rocky intertidal zone. 

PMID- 26194237
TI  - PCBs in schools--where communities and science come together.
AB  - A novel aspect of the 8th International PCB Workshop at Woods Hole, MA, was the
      interaction between scientists and activists. While earlier workshops in this
      series had mentioned policy making, this Workshop focused on the problem of PCBs
      in schools. Focus on a problem brought an activist to give a plenary talk and
      facilitated a 1-day registration for other non-scientists to attend. The workshop
      was cohosted by the Superfund Research Programs at University of Iowa and Boston
      University and included active participation of each Program's Research
      Translation and Community Engagement Cores. A mandate of each National Institute
      of Environmental Health Science (NIEHS)-funded Superfund Research Program is
      bidirectional communication between scientists and community groups. The authors
      describe the events leading up to community involvement in the Workshop and the
      substance of the community engagement aspects of the workshop, in particular the
      participation by a parent-teacher group, Malibu Unites. The authors also discuss
      the value of such communication in terms of making important research accessible
      to those who are most affected by the results and poised to use it and the value
      of making scientists aware of the important role they play in society in
      addressing difficult questions that originate in community settings. 

PMID- 26194234
TI  - The uptake and bioaccumulation of heavy metals by food plants, their effects on
      plants nutrients, and associated health risk: a review.
AB  - Heavy metal contamination is a globally recognized environmental issue,
      threatening human life very seriously. Increasing population and high demand for
      food resulted in release of various contaminants into environment that finally
      contaminate the food chain. Edible plants are the major source of diet, and their
      contamination with toxic metals may result in catastrophic health hazards. Heavy
      metals affect the human health directly and/or indirectly; one of the indirect
      effects is the change in plant nutritional values. Previously, a number of review
      papers have been published on different aspects of heavy metal contamination.
      However, no related information is available about the effects of heavy metals on
      the nutritional status of food plants. This review paper is focused upon heavy
      metal sources, accumulation, transfer, health risk, and effects on protein, amino
      acids, carbohydrates, fats, and vitamins in plants. The literature about heavy
      metals in food plants shows that both leafy and nonleafy vegetables are good
      accumulators of heavy metals. In nonleafy vegetables, the bioaccumulation pattern
      was leaf > root ~ stem > tuber. Heavy metals have strong influence on nutritional
      values; therefore, plants grown on metal-contaminated soil were nutrient
      deficient and consumption of such vegetables may lead to nutritional deficiency
      in the population particularly living in developing countries which are already
      facing the malnutrition problems. 

PMID- 26194238
TI  - Solid surface photochemistry of montmorillonite: mechanisms for the arsenite
      oxidation under UV-A irradiation.
AB  - Transformation of inorganic arsenic species has drawn great concern in recent
      decades because of worldwide and speciation-dependent pollution and the hazards
      that they pose to the environment and to human health. As(III) photooxidation in
      aquatic systems has received much attention, but little is known about
      photochemical transformation of arsenic species on top soil. As(III)
      photooxidation on natural montmorillonite under UV-A radiation was investigated
      by using a moisture- and temperature-controlled photochemical chamber with two
      black-light lamps. Initial As(III) concentration, pH, layer thickness, humic acid
      (HA) concentration, the presence of additional iron ions, and the contribution of
      reactive oxygen species (ROS) were examined. The results show that pH values of
      the clay layers greatly influenced As(III) photooxidation on montmorillonite.
      As(III) photooxidation followed the Langmuir-Hinshelwood model. HA and additional
      iron ions greatly promoted photooxidation, but excess Fe(II) competed with
      As(III) for oxidation by ROS. Scavenging experiments revealed that natural
      montmorillonite induced the conversion of As(III) to As(V) by generating ROS
      (mainly HO(*) and HO2(*)/O2(*-)) and that HO(*) radical was the predominant
      oxidant in this system. Our work demonstrates that photooxidation on the surface
      of natural clay minerals in top soil can be important to As(III) transformation.
      This allows understanding and predicting the speciation and behavior of arsenic
      on the soil surface.

PMID- 26194239
TI  - Air sampling of flame retardants based on the use of mixed-bed sorption tubes--a
      validation study.
AB  - An analytical methodology using automatic thermal desorption and gas
      chromatography mass spectrometry analysis was optimized and validated for
      simultaneous determination of a set of components from three different flame
      retardant chemical classes: polybrominated diphenyl ethers (PBDEs) (PBDE-28, PBDE
      47, PBDE-66, PBDE-85, PBDE-99, PBDE-100), organophosphate flame retardants (PFRs)
      (tributyl phosphate, tripropyl phosphate, tris(2-chloroethyl)phosphate-, tris(1,3
      dichloro-2-propyl) phosphate, tris(2-ethylhexyl) phosphate, triphenyl phosphate,
      tris(2-chloro-1-methylethyl) phosphate and tricresylphosphate), and "novel"
      brominated flame retardants (NBFRs) (pentabromotoluene, 2,3,4,5,6
      pentabromoethylbenzene, (2,3-dibromopropyl) (2,4,6-tribromophenyl) ether,
      hexabromobenzene, and 2-ethylhexyl 2,3,4,5-tetrabromobenzoate) in air. The
      methodology is based on low volume active air sampling of gaseous and particulate
      air fractions on mixed-bed (polydimethylsiloxane (PDMS)/Tenax TA) sorption tubes.
      The optimized method provides recoveries >88%; a limit of detection in the range
      of 6-25 pg m(-3) for PBDEs, 6-171 pg m(-3) for PFRs, and 7-41 pg m(-3) for NBFRs;
      a linearity greater than 0.996; and a repeatability of less than 10% for all
      studied compounds. The optimized method was compared with a standard method using
      active air sampling on XAD-2 sorbent material, followed by liquid extraction. On
      the one hand, the PDMS/Tenax TA method shows comparable results at longer
      sampling time conditions (e.g., indoor air sampling, personal air sampling). On
      the other hand, at shorter sampling time conditions (e.g., sampling from emission
      test chambers), the optimized method detects up to three times higher
      concentrations and identifies more flame retardant compounds compared to the
      standard method based on XAD-2 loading.

PMID- 26194240
TI  - Analysis of ambient formaldehyde in the eastern region of India along Indo
      Gangetic Plain.
AB  - Ambient levels of formaldehyde (HCHO) were measured in the tropical urban mega
      city of Kolkata from July 2012 to April 2014, based on USEPA Compendium Method TO
      11A using 2,4-dinitrophenylhydrazine (2,4-DNPH). The samples were analyzed by
      isocratic reverse-phase high-performance liquid chromatography (HPLC) with an
      ultraviolet detector at a wavelength of 360 nm. High values of HCHO were recorded
      at our site. The highest and average HCHO mixing ratio measured for the entire
      study period was 803 and 217 ppbv respectively. Seasonal wind regimes have been
      found to influence the seasonal pattern of HCHO mixing ratio at this site
      resulting in relatively higher mixing ratio of HCHO during the pre-monsoon
      periods as compared to the others. Apart from these, sampling-based measurements
      of CH4 and continuous measurements of ozone (O3) and CO were also performed with
      the objective to study the interrelationship of HCHO with these species. The
      results suggest the presence of highly complex chemistry among them.

PMID- 26194241
TI  - Removal of Microcystis aeruginosa using nano-Fe3O4 particles as a coagulant aid.
AB  - Blue-green algae bloom is of great concern globally since they adversely affect
      the water ecosystem and also drinking water treatment processes. This work
      investigated the removal of Microcystis aeruginosa (M. aeruginosa) by combining
      the conventional coagulant polyaluminum chloride (PACl) with nano-Fe3O4 particles
      as a coagulant aid. The results showed that the addition of nano-Fe3O4
      significantly improved the removal efficiency of M. aeruginosa by reducing the
      amount of PACl dosage and simultaneously hastening the sedimentation. At the M.
      aeruginosa density of an order of magnitude of 10(7), 10(6), and 10(5) pcs/mL,
      respectively, the corresponding PACl dose of 200, 20, and 2 mg/L and the mass
      ratio of PACl to nano-Fe3O4 of 4:1, the removal efficiency of M. aeruginosa could
      be increased by 33.0, 44.7, and 173.1%, respectively. Compared to PACl, PACl
      combined with the nano-Fe3O4 as a coagulant aid had higher removal efficiency at
      a wider pH range. SEM images showed that nano-Fe3O4 first combined with PACl to
      form clusters and further generated the flocs with algae. Results from the laser
      particle analyzer further suggested that the floc size increased with the
      addition of nano-Fe3O4. It was noted that the addition of nano-Fe3O4 led to
      aluminum species change after PACl hydrolyzed in the algae solution, from Ala to
      Alb and Alc subsequently. As a coagulant aid, the nano-Fe3O4, in conjunction with
      PACl, apparently provided nucleation sites for larger flocs to integrate with M.
      aeruginosa. In addition, increased floc density improved the removal of M.
      aeruginosa.

PMID- 26194242
TI  - Selective and comprehensive analysis of organohalogen compounds by GC * GC
      HRTofMS and MS/MS.
AB  - Thousands of organohalogen compounds, including hazardous chemicals such as
      polychlorinated biphenyls (PCBs) and other persistent organic pollutants (POPs),
      were selectively and simultaneously detected and identified with simple, or no,
      purification from environmental sample extracts by using several advanced
      methods. The methods used were software extraction from two-dimensional gas
      chromatography-high-resolution time-of-flight mass spectrometry (GC * GC-HRTofMS)
      data, measurement by negative chemical ionization with HRTofMS, and neutral loss
      scanning (NLS) with GC * GC-MS/MS. Global and selective detection of
      organochlorines and bromines in environmental samples such as sediments and fly
      ash was achieved by NLS using GC * GC-MS/MS (QQQ), with the expected losses of
      35Cl and 79Br. We confirmed that negative chemical ionization was effective for
      sensitive and selective ionization of organohalogens, even using GC * GC-HRTofMS.
      The 2D total ion chromatograms obtained by using negative chemical ionization and
      selective extraction of organohalogens using original software from data measured
      by electron impact ionization were very similar; the software thus functioned
      well to extract organohalogens. Combining measurements made by using these
      different methods will help to detect organohalogens selectively and globally.
      However, to compare the data obtained by individual measurements, the retention
      times of the peaks on the 2D chromatograms need to match.

PMID- 26194243
TI  - Effects of drought on cadmium accumulation in peanuts grown in a contaminated
      calcareous soil.
AB  - This study aimed to investigate the effects of drought stress on cadmium (Cd)
      accumulation in peanut (Arachis hypogaea L.) grown in contaminated calcareous
      soils. Five peanut cultivars were grown in a calcareous soil spiked with 4 mg Cd
      kg(-1) soil (dry weight) under well-watered, mild drought, and severe drought
      conditions. The biomass production, gas exchange, spectral reflectance, and Cd
      accumulation in plant tissues were determined. The five cultivars significantly
      differed from each other in biomass production, gas exchange, spectral
      reflectance, and Cd accumulation. The effect of drought on Cd accumulation in
      peanuts varies with plant tissues, cultivars, and developmental stages. Drought
      decreased root Cd concentrations in seedlings of the two high Cd-accumulating
      cultivars (Haihua 1 and Zhenghong 3), which is associated with increasing leaf
      active Fe content. However, for the mature plants, drought stress caused an
      increase in Cd accumulation in roots, pod walls, and seeds depending on peanut
      cultivars. Negative correlations were found between seed Cd concentration and
      biomasses in both preflowering seedlings and mature plants. The seed Cd
      concentration in mature plants was also observed to be positively correlated with
      the shoot Cd concentration in preflowering seedlings. The increased Cd
      concentration in seeds of drought-stressed peanut plants grown in Cd-contaminated
      calcareous soils might be attributed to the drought-induced decrease of biomass
      production.

PMID- 26194244
TI  - Antimony (SbIII) reduces growth, declines photosynthesis, and modifies leaf
      tissue anatomy in sunflower (Helianthus annuus L.).
AB  - The role of antimony (Sb)--a non-essential trace metalloid--in physiological
      processes running in crops is still poorly understood. Present paper describes
      the effect of Sb tartrate (SbIII) on growth, Sb uptake, photosynthesis,
      photosynthetic pigments, and leaf tissue organization in young sunflower plants
      grown in hydroponics. We found that growth of below- and aboveground part was
      reduced with increasing concentration of Sb in the medium. Although Sb was mostly
      taken up by sunflower roots and only small part (1-2%) was translocated to the
      shoots, decline in photosynthesis, transpiration, and decreased content of
      photosynthetic pigments were observed. This indicates that despite relatively low
      mobility of Sb in root-shoot system, Sb in shoot noticeably modifies
      physiological status and reduced plant growth. Additionally, leaf anatomical
      changes indicated that Sb reduced the size of intercellular spaces and made leaf
      tissue more compact.

PMID- 26194245
TI  - Evaluation of labor-related pelvic floor changes 3 months after delivery: a 3D
      transperineal ultrasound study.
AB  - INTRODUCTION AND HYPOTHESIS: The levator hiatus and puborectalis muscle play a
      critical role in supporting the pelvic organs. Vaginal birth is known to be the
      main etiological factor for development of levator defects. The aim of this study
      was to define and evaluate changes in the levator ani immediately and at 3 months
      after delivery with 3D transperineal ultrasonography. METHODS: Of 92 eligible
      primiparous women who delivered vaginally, 84 were examined within 36 h of
      delivery (early evaluation) and 3 months after delivery (late evaluation) with 3D
      transperineal ultrasonography. 3D volumes were evaluated in the supine position
      after voiding. Levator biometry, levator defect and loss of tenting were
      determined in the axial plane. RESULTS: The levator defect rate was significantly
      higher at the early evaluation (71.4 %) than at the late evaluation (39.6 %; p <
      0.0001). Levator thickness and transverse hiatal diameters on resting and during
      maximal Valsalva maneuver were greater at the late evaluation than at the early
      evaluation. Anteroposterior hiatal dimension, hiatal area on resting and maximal
      during the Valsalva maneuver were greater at the early evaluation than at the
      late evaluation. Head circumference and the length of the first stage of labor
      were associated with levator defects. CONCLUSIONS: Changes in the levator hiatus
      could be transitional or persist over time. There were significant changes in
      levator hiatus measurements, levator thickness, levator defect incidence and loss
      of tenting rate between early postpartum and late postpartum. The head
      circumference of the fetus and the length of the first stage of labor are the
      shared and consistent factors that can be associated with pelvic floor trauma.

PMID- 26194247
TI  - Risk factors for methicillin-resistant Staphylococcus aureus skin and soft tissue
      infection in MRSA-colonized patients discharged from a Veterans Affairs hospital.
AB  - Currently, limited studies have quantified the risk of methicillin-resistant
      Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) for MRSA
      colonized patients on discharge from hospital. Our retrospective, case-control
      study identified independent risk factors for the development of MRSA SSTIs among
      such patients detected by active MRSA nasal screening in an acute care hospital
      by PCR on admission, and bacteriological cultures on discharge. Cases were MRSA
      colonized patients aged ?18 years who developed a MRSA SSTI post-discharge and
      controls were those who did not develop a MRSA SSTI post-discharge. Controls were
      matched to cases by length of follow-up (+/-10 days) for up to 18 months.
      Potential demographic and clinical risk factors for MRSA infection were
      identified using electronic queries and manual chart abstraction; data were
      compared by standard statistical tests and variables with P values ?0.05 in
      bivariable analysis were entered into a logistic regression model. Multivariable
      analysis demonstrated prior hospital admission within 12 months (P = 0.02), prior
      MRSA infection (P = 0.05), and previous myocardial infarction (P = 0.01) were
      independently predictive of a MRSA SSTI post-discharge. Identification of MRSA
      colonization upon admission and recognition of risk factors could help identify a
      high-risk population that could benefit from MRSA SSTI prevention strategies. 

PMID- 26194246
TI  - Molecular basis of claudin-17 anion selectivity.
AB  - Claudin-17 is a paracellular channel-forming tight junction protein. Unlike the
      cation channels claudin-2 and -15, claudin-17 forms a distinct anion-selective
      channel. Aim of this study was to determine the molecular basis of channel
      formation and charge selectivity of this protein. To achieve this, residues
      located in the extracellular loops (ECL) 1 and 2 of claudin-17 were substituted,
      preferably those whose charges differed in claudin-17 and in claudin-2 or -15.
      The respective mutants were stably expressed in MDCK C7 cells and their ability
      to form charge-selective channels was analyzed by measuring ion permeabilities
      and transepithelial electrical resistance. The functional data were combined with
      homology modeling of the claudin-17 protomer using the structure of claudin-15 as
      template. In ECL1, K65, R31, E48, and E44 were found to be stronger involved in
      Cldn17 channel function than the clustered R45, R56, R59, and R61. For K65, not
      only charge but also stereochemical properties were crucial for formation of the
      anion-selective channel. In ECL2, both Y149 and H154 were found to contribute to
      constitution of the anion channel in a distinct manner. In conclusion, we provide
      insight into the molecular mechanism of the formation of charge- and size
      selective paracellular ion channels. In detail, we propose a hydrophilic furrow
      in the claudin-17 protomer spanning from a gap between the ends of TM2 and TM3
      along R31, E48, and Y67 to a gap between K65 and S68 lining the anion channel. 

PMID- 26194248
TI  - Effect of Knockout of Mdr1a and Mdr1b ABCB1 Genes on the Systemic Exposure of a
      Doxorubicin-Conjugated Block Copolymer in Mice.
AB  - We previously elucidated that ATP-binding cassette subfamily B member 1 (ABCB1)
      mediates the efflux of doxorubicin-conjugated block copolymers from HeLa cells.
      Here, we investigated the role of ABCB1 in the in vivo behavior of a doxorubicin
      conjugated polymer in Mdr1a/1b(-/-) mice. The area under the curve for
      intravenously administered polymer in Mdr1a/1b(-/-) mice was 2.2-fold greater
      than that in wild-type mice. The polymer was mostly distributed in the liver
      followed by spleen and less so in the brain, heart, kidney, and lung. The amount
      of polymer excreted in the urine was significantly decreased in Mdr1a/1b(-/-)
      mice. The amounts of polymers excreted in the feces were similar in both groups
      despite the higher systemic exposure in Mdr1a/1b(-/-) mice. Confocal microscopy
      images showed polymer localized in CD68(+) macrophages in the liver. These
      results show that knockout of ABCB1 prolonged systemic exposure of the
      doxorubicin-conjugated polymer in mice. Our results suggest that ABCB1 mediated
      the excretion of doxorubicin-conjugated polymer in urine and feces. Our results
      provide valuable information about the behavior of block copolymers in vivo,
      which is important for evaluating the pharmacokinetics of active substances
      conjugated to block copolymers or the accumulation of block copolymers in vivo. 

PMID- 26194249
TI  - Impact of single-incision laparoscopic cholecystectomy (SILC) versus conventional
      laparoscopic cholecystectomy (CLC) procedures on surgeon stress and workload: a
      randomized controlled trial.
AB  - INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) may lead to
      higher patient satisfaction; however, SILC may expose the surgeon to increased
      workload. The goal of this study was to compare surgeon stress and workload
      between SILC and conventional laparoscopic cholecystectomy (CLC). METHODS: During
      a double-blind randomized controlled trial comparing patient outcomes for SILC
      versus CLC (NCT0148943), surgeon workload was assessed by four measures: surgery
      task load index questionnaire (Surg-TLX), maximum heart rate, salivary cortisol
      level, and instruments usability survey. The maximum heart rate and salivary
      cortisol levels were sampled from the surgeon before the random assignment of the
      surgical procedure, intraoperatively after the cystic duct was clipped, and at
      skin closure. After each procedure, the surgeon completed the Surg-TLX and an
      instrument usability survey. Student's t tests, Wilcoxon rank sum test, and
      Kruskal-Wallis nonparametric ANOVAs on the dependent variables by the technique
      (SILC vs. CLC) were performed with alpha = 0.05. RESULTS: Twenty-three SILC and
      25 CLC procedures were included in the intent-to-treat analysis. No significant
      differences were observed between SILC and CLC for patient demographics and
      procedure duration. SILC had significantly higher post-surgery surgeon maximum
      heart rates than CLC (p < 0.05). SILC also had significantly higher mean change
      in the maximum heart rate between during and post-procedure (p < 0.05) than CLC.
      Salivary cortisol level was significantly higher during SILC than CLC (p < 0.01).
      Awkward manipulation of the instruments and limited fine motions were reported
      significantly more frequently with SILC than CLC (p < 0.01). In the surgeon
      reported Surg-TLX, subscale of physical demand was significantly more demanding
      for SILC than CLC (p < 0.05). CONCLUSIONS: Surgeon heart rate, salivary cortisol
      level, instrument usability, and Surg-TLX ratings indicate that SILC is
      significantly more stressful and physically demanding than the CLC. Surgeon
      stress and workload may impact patients' outcomes; thus, ergonomic improvement on
      SILC is necessary.

PMID- 26194250
TI  - A prospective 1-year comparative study of transaxillary total thyroidectomy
      regarding functional outcomes: Is it really promising?
AB  - BACKGROUND: The purpose of this study was to evaluate postoperative voice
      outcomes and functional parameters in total thyroidectomy via a transaxillary
      (TA) approach. METHODS: Seventy-six patients who underwent total thyroidectomy
      via a TA approach (TA group) were included. A total of 204 patients who underwent
      conventional open total thyroidectomy (conventional group) in the same time
      period were analyzed as a control group. All patients underwent prospective
      functional evaluations before surgery and at 1 week and 1, 3, 6, and 12 months
      postoperatively using a comprehensive battery of functional assessments. RESULTS:
      There was no conversion to conventional open thyroidectomy in the TA group.
      Operation time and the amount of drainage were significantly higher in the TA
      group than in the conventional group (p < 0.001 and p = 0.033, respectively),
      while vocal cord paralysis, hypoparathyroidism, and hematoma were not different
      among two groups (p = 0.215, 0.290, and 0.385, respectively). Regarding GRBAS,
      the TA group showed a more aggravated tendency postoperatively, although
      statistical significance was attained only at postoperative 6 months (p = 0.043).
      The voice handicap index abruptly increased postoperatively in the TA group,
      showing significant differences with the conventional group at postoperative 1
      week and 1 month (p < 0.001 and p = 0.001, respectively). Fundamental frequency
      and maximal vocal pitch did not significantly change postoperatively in either
      group. The conventional group showed a more rapid decline in pain than the TA
      group, and paresthesias on the neck and chest were more aggravated in the TA
      group during the early postoperative period. The dysphagia handicap index was
      higher in the TA group, while cosmesis was better in the TA group at all
      postoperative periods. CONCLUSIONS: Although cosmetic outcome was better with the
      TA approach, the longer operation time, aggravated subjective voice outcomes,
      paresthesia, and swallowing function need to be considered in selecting the
      operative approach.

PMID- 26194251
TI  - Laparoscopic narrow band imaging for detection of occult cancer metastases: a
      randomized feasibility trial.
AB  - BACKGROUND: Selection of cancer treatment fundamentally relies on staging of the
      underlying malignancy. The aim of this study was to evaluate the feasibility and
      effectiveness of laparoscopic narrow band imaging (NBI) for operative staging and
      detection of occult peritoneal cancer metastases. METHODS: A randomized,
      controlled feasibility trial with crossover design evaluating adult patients with
      gastrointestinal or gynecologic malignancies who have a clinical indication for
      diagnostic laparoscopy was conducted. Twenty-three patients were randomized to
      white-light followed by NBI laparoscopy (n = 11) or NBI followed by white-light
      laparoscopy (n = 12) using the Olympus Evis Exera II system. Three patients were
      excluded from analysis. RESULTS: In all 20 study patients, the abdominal cavity
      was sufficiently illuminated. An enhanced contrast of microvasculature and organ
      surface pattern was appreciated. Eight of the 20 patients (40%) were found to
      have metastases of the peritoneal surface. While NBI did not show any additional
      peritoneal lesions, 2 of the 63 suspicious-appearing nodules seen on white-light
      imaging were not visible on NBI (p = 0.50). The median diameter of all the
      nodules identified was 2 mm (range 1-50 mm) and was identical with each method.
      CONCLUSIONS: The information from this feasibility study demonstrated that NBI
      provides adequate illumination of the abdominal cavity and a unique contrast that
      enhances microvasculature and architectural surface pattern. The results suggest
      that NBI laparoscopy is not superior in detecting peritoneal metastases compared
      to standard white-light laparoscopy, but might provide a technology that could be
      applied for other abdominal pathologies.

PMID- 26194252
TI  - A multimodal, one-session endoscopic approach for management of patients with
      advanced pancreatic cancer.
AB  - BACKGROUND: A number of patients with inoperable pancreatic cancer may
      concurrently complain of pain, biliary obstruction, and duodenal stenosis.
      Endoscopic palliative treatments and opioid therapy are generally performed in
      these patients. The study aimed to assess the efficacy and safety of a multimodal
      'one-Session Three Endoscopic Procedures' (one-STEP) to simultaneously treat
      cholestasis, restore duodenal transit, and achieve pain relief in selected
      patients with advanced pancreatic cancer. METHODS: Selected patients diagnosed
      with an advanced pancreatic cancer presenting with biliary obstruction, duodenal
      stenosis, and severe pain treated with the one-STEP were considered. The one-STEP
      endoscopic approach included biliary and duodenal stenting, and EUS-guided celiac
      plexus neurolysis. The technical success rate, complications, pain relief, and
      opioid use at follow-up were assessed. RESULTS: A total of 15 patients were
      treated. The one-STEP was successful in 13 (87 %) cases, while it failed in two
      patients due to the impossibility of dilating the neoplastic mass for creating a
      fistula. No endoscopy-related complications occurred. The median of pain
      intensity was 8 (range 7-10) at entry and significantly decreased to 2 (range 2
      4) 72 h following celiac plexus neurolysis. At follow-up (median survival 4
      months; range 3-8), only 3 (20 %) needed of narcotic treatment in the last
      period. CONCLUSIONS: The multimodal one-STEP is an effective and safe endoscopic
      approach for palliative treatment of biliary and duodenal stenosis, and for
      relieving chronic pain in patients with advanced pancreatic cancer.

PMID- 26194253
TI  - Biomolecular inflammatory response to surgical energy usage in laparoscopic
      surgery: results of a randomized study.
AB  - OBJECTIVE: Use of surgical energy is integral to laparoscopic surgery (LS).
      Energized dissection (ED) has a potential to impact the biomolecular expression
      of inflammation due to ED-induced collateral inflammation. We did this triple
      blind randomized controlled (RCT) study to assess this biomolecular footprint in
      an index LS, i.e., laparoscopic cholecystectomy (LC). METHODS AND PROCEDURES:
      This RCT was conducted in collaboration with tertiary-level institutions, from
      January 2014 to December 2014 with institutional review board clearance.
      Consecutive, unselected, consenting candidates for LC were randomized (after
      anesthesia induction) into group I (ED) and group II (non-ED). They were managed
      with compliance to universal protocols for ethics, informed consent, anesthesia,
      drug usage and clinical pathway with blinded observers. Biomolecular inflammatory
      markers, i.e., interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and
      highly sensitive CRP (HS-CRP), were measured with blood drawn juxta
      preoperatively (H0), at 4 h (H4) and at 24 h (H24). The quantitative changes
      induced by ED on IL-6, TNF-alpha and HS-CRP at H0, H4 and H24 with their kinetic
      behavior were the study endpoint. Prospective data were analyzed statistically
      with a p value of <0.05 being significant. RESULTS: Two cases from the ED group
      had biliary injury and hence were withdrawn from analysis. The ED (n = 49) and
      non-ED (n = 51) groups had similar demographic, clinical and H0 biomolecular
      variables. There was a significant increase in IL-6, TNF-alpha and HS-CRP from H0
      to H4 in both the groups (p values <0.001). From H4 to H24, all three cytokines
      showed significant increase in ED group (p < 0.05), whereas in the non-ED group,
      IL-6 showed significant fall (p = 0.004) and TNF-alpha showed no significant
      change (p = 0.063). Both the groups showed H4-H24 elevation of HS-CRP (p =
      0.000). CONCLUSION: Energized dissection adds to the cytokine-mediated
      postoperative inflammation. The additional ED-induced inflammation can be
      measured objectively by IL-6 and TNF-alpha levels. CLINICAL TRIALS REGISTRY:
      Clinical Trials Registry, India (REF/2014/06/007153).

PMID- 26194254
TI  - The uncinate process first approach: a novel technique for laparoscopic right
      hemicolectomy with complete mesocolic excision.
AB  - BACKGROUND: Current evidence suggests that complete mesocolic excision (CME) for
      right-sided colon cancer could be beneficial in terms of long-term survival.
      However, CME is a considerably more complex operation than standard right
      hemicolectomy; this is especially true for the laparoscopic approach.
      Consequently, we have explored a new laparoscopic approach that provides surgical
      radicality at the mesenteric root on the one hand and maximum safety on the other
      hand. METHODS: The key feature of the uncinate process first approach (UFA) is
      the commencement of the dissection at the fourth part of the duodenum using a
      medial to lateral approach, thus mobilizing the whole mesenteric root posteriorly
      before the central parts of the mesenteric vessels are accessed. Twenty-eight
      selected patients with right-sided colon cancer underwent surgery using the UFA
      and were compared with 51 patients who underwent an open CME procedure (CON). In
      11/28 and 51/51 patients in the UFA and CON groups, respectively, a planimetric
      assessment of the specimen was performed. RESULTS: Surgical time was longer
      (144.8 vs. 202.5 min; p < 0.000) and postoperative stay shorter (8.0 vs. 10.5
      days; p < 0.01) for the laparoscopic approach. The area of the resected mesentery
      (UFA, 15,097 mm(2); CON, 15,788 mm(2); p = 0.47) and the lymph node count (UFA,
      59.0; CON, 51.0; p = 0.09) was not significantly different; additionally, no
      difference was observed regarding anastomotic leakage (both n = 0) and
      postoperative mortality (UFA, 0/28; CON, 1/51; p = 1.0). CONCLUSION: Laparoscopic
      right hemicolectomy with CME using the UFA provides adequate radicality according
      to the CME principles and seems feasible and as safe as an open technique.
      However, future trails will have to demonstrate whether the theoretical
      advantages of the UFA, with a higher degree of mobility and accessibility of the
      mesenteric root, translate into a significant clinical benefit, especially
      relative to the other laparoscopic techniques.

PMID- 26194255
TI  - Laparoscopic versus open major hepatectomy for hepatocellular carcinoma: a
      matched pair analysis.
AB  - BACKGROUND: Laparoscopic major hepatectomy (LMH) for hepatocellular carcinoma
      (HCC) is currently perceived a complex and challenging laparoscopic procedure and
      is limited to a few expert teams. This study analyzed the short- and long-term
      outcomes of LMH for HCC compared with open hepatectomy. METHODS: From January
      2006 to May 2014, 38 patients underwent LMH for HCC (10 left and 28 right
      hepatectomy). They were matched and compared to 38 patients (10 left and 28 right
      hepatectomy) who underwent a conventional open approach. Short-term operative and
      postoperative outcomes as well as long-term outcomes, including disease-free
      survival and overall survival rates, were evaluated. RESULTS: Patients were well
      matched for several preoperative factors. Overall complication rates were
      significantly higher for the open group. No significant difference was seen in 3
      year overall survival between the open and laparoscopic groups (69.2 vs. 73.4 %;
      p = 0.951). A trend toward better 3-year disease-free survival after laparoscopy
      was observed (29.7 vs. 50.3 %; p = 0.219), even though the difference did not
      reach statistical significance. The same trend was seen in subgroup analyses of
      right and left hepatectomy. CONCLUSIONS: This study shows the feasibility of LMH
      for HCC compared to open hepatectomy in regard to both short- and long-term
      outcomes. LMH offers many advantages commonly attributed to laparoscopy and is
      well suited for HCC with cirrhosis when performed by experienced surgeons.

PMID- 26194256
TI  - Non-alcoholic fatty liver disease resolution following sleeve gastrectomy.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a disease highly prevalent
      among the morbidly obese population, is one of the most common causes of chronic
      liver disease today. The purpose of this study was to observe the effect of
      laparoscopic sleeve gastrectomy (LSG) on the resolution of NAFLD. METHODS: A
      retrospective study was conducted of 84 patients diagnosed with NAFLD prior to
      undergoing LSG. The diagnosis of NAFLD was achieved based on transabdominal
      ultrasonographic imaging as per the 2012 joint guidelines for the diagnosis of
      NAFLD (American Gastroenterological Association, American Association for the
      Study of Liver Diseases, and American College of Gastroenterology). The patients
      had follow-up anthropometric measurements and were re-evaluated with
      postoperative ultrasounds at different time frames to assess the resolution of
      the disease. RESULTS: The median age of the patients was 44 (17-62), and 66.7 %
      were female. Average time since surgery was 3.3 years (range 1-5 years). The mean
      pre- and postoperative BMIs were 46.6 +/- 7.8 and 33.0 +/- 7.1, respectively,
      with a mean percent excess weight loss (%EWL) of 55.7 % +/- 23.0. A total of 47
      (56 %) patients showed complete resolution of NAFLD postoperatively. Multivariate
      analysis showed a significant resolution of NAFLD in patients achieving >50 % EWL
      (OR 10.1; p < 0.001) after controlling for age and sex. CONCLUSIONS: Weight loss
      after LSG effectively resolved NAFLD in more than half of the obese patients in
      this study and can prove to be a useful tool in tackling the disease in the
      future.

PMID- 26194258
TI  - Importance of pouch size in laparoscopic Roux-en-Y gastric bypass: a cohort study
      of 14,168 patients.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most
      common bariatric procedures worldwide, but the importance of gastric pouch size
      is still under debate. We have studied how pouch size affects risk of marginal
      ulcer and excess body mass index loss (EBMIL%) at 6 weeks and 1 year
      postoperatively. METHODS: Scandinavian Obesity Surgery Registry included 14,168
      LRYGB patients with linear stapled gastrojejunostomies, having complete pre- and
      postoperative data concerning length of stapler needed to complete the gastric
      pouch, incidence of marginal ulcers and weight loss. LRYGB technique in Sweden is
      highly standardized, and total length of stapler was used as a proxy for pouch
      size. RESULTS: Mean length of stapler used for the pouch was 145 mm. At 1 year,
      symptomatic marginal ulcers were noted in 0.9 % of the patients. The relative
      risk of marginal ulcer increased by 14 % (95 % confidence interval 9-20 %), for
      each centimeter of stapler used for the pouch. Body mass index (BMI) was reduced
      from 42.4 +/- 5.1 to 36.1 kg/m(2) at 6 weeks and 28.9 kg/m(2) at 1 year. The
      total length of stapler predicted EBMIL% at 6 weeks but not at 1 year. Female
      gender, low preoperative BMI, young age and absence of diabetes predicted better
      EBMIL% at 1 year. CONCLUSION: A smaller pouch reduces the risk of marginal
      ulcers, but does not predict better weight loss at 1 year. Additional stapling
      should be avoided as each extra centimeter increases the relative risk of
      marginal ulcers by 14 %.

PMID- 26194257
TI  - Safety and feasibility of laparoscopic liver resection with associated
      lymphadenectomy for intrahepatic cholangiocarcinoma: a propensity score-based
      case-matched analysis from a single institution.
AB  - BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is still a relatively uncommon
      indication for laparoscopic surgery because of technical challenges related to
      the frequent need for major hepatectomies and the necessity to perform formal
      regional lymphadenectomy. The aim of the present case-matched study was to
      compare laparoscopic and open resections for ICC. METHODS: In a case-matched
      retrospective analysis, 20 consecutive patients who had undergone laparoscopic
      resection for ICC (LPS group) were compared with 60 of 83 patients who had
      undergone open surgery (open group) in the same institution. The groups were
      matched in a ratio of 1:3 using propensity scores based on covariates
      representing relevant patient characteristics and severity of disease. The main
      endpoints were short- and long-term outcomes and impact and adequacy of
      laparoscopic lymphadenectomy. RESULTS: The groups were well matched in terms of
      patient and disease characteristics. The laparoscopic approach resulted in less
      blood loss (200 vs. 350 mL, p = 0.040) despite less extensive use of the Pringle
      maneuver. There was no difference in perioperative morbidity and mortality rates;
      however, the laparoscopic approach was associated with faster functional recovery
      (median 3 vs. 4 days, p = 0.050). After a mean follow-up of 39 months, disease
      free and overall survivals were 33 and 51 months, respectively, for the LPS and
      36 and 63, respectively, for the open group (p ns). The number of harvested nodes
      was comparable between groups. CONCLUSIONS: Compared with open surgery,
      laparoscopic resection of ICC is feasible and safe, providing short-term benefits
      without negatively affecting oncologic adequacy in terms of rate of R0
      resections, depth of margins, and long-term overall and disease-free survivals.
      Laparoscopic regional lymphadenectomy is technically possible but should be the
      object of future focused studies.

PMID- 26194259
TI  - Revision endoscopic stapler Zenker's diverticulotomy.
AB  - BACKGROUND: Endoscopic stapler diverticulotomy (ESD) has become an accepted
      primary treatment for Zenker's diverticulum (ZD). Recurrence of symptoms after
      surgical treatment of ZD is not uncommon, and traditionally patients with
      recurrent symptomatic ZD were referred to revision surgery by the transcervical
      Zenker's diverticulectomy approach. Our objective was to evaluate the technical
      feasibility, safety and effectiveness of revision endoscopic stapler
      diverticulotomy (RESD) for recurrent ZD. METHODS: A case series with chart review
      study conducted in a tertiary referral center. The records of all patients who
      underwent ESD at our institute between 2002 and 2013 were retrieved and those who
      underwent RESD were identified and screened for primary surgical history,
      symptoms of recurrent ZD, time to recurrence, intraoperative and postoperative
      RESD course, complications and symptom resolution. The surgical history and
      outcome results of RESD and primary ESD (PESD) patients were compared. RESULTS:
      Eighty-nine ESDs were performed. Twenty were RESDs for recurrent ZD, and 69 were
      PESDs. Nine RESDs were performed for recurrent ZD after transcervical Zenker's
      diverticulectomy, 10 RESDs for recurrent ZD after ESD, and one initial surgical
      approach was unknown. The mean time from first operation for ZD to RESD was 4.7
      years. The average RESD surgery time and hospital stay were 21.4 min and 2.8
      days, respectively. Endoscopic stapling of the ZD was feasible in 19 of 20 RESDs.
      Relief of symptoms without recurrence was achieved after 18 RESDs. Four RESD
      patients experienced minor postoperative complications. There were no significant
      differences in operative time, technical feasibility, hospital stay and
      complication rate between the RESD and PESD groups (P > .05). CONCLUSION: RESD
      for ZD is technically feasible, safe and effective. The results are comparable to
      those of PESD.

PMID- 26194260
TI  - The impact of postoperative complications on the recovery of elderly surgical
      patients.
AB  - BACKGROUND: While the negative impact of postoperative complications on hospital
      costs, survival, and cancer recurrence is well known, few studies have quantified
      the impact of postoperative complications on patient-centered outcomes such as
      functional status. The objective of this study was to estimate the impact of
      postoperative complications on recovery of functional status after elective
      abdominal surgery in elderly patients. METHODS: Elderly patients (70 years and
      older) undergoing elective abdominal surgery, with a planned length of stay >1
      day, were prospectively enrolled between July 2012 and December 2014. The primary
      outcome was time to recovery to the preoperative functional status measured by
      the short physical performance battery (SPPB) preoperatively and at 1 week, 1, 3,
      and 6 months after surgery. The comprehensive complication index was calculated
      to grade the severity and number of postoperative complications. A Weibull
      survival model with interval censoring was performed, controlling for age, sex,
      body mass index (BMI), comorbidities (Charlson comorbidity index-CCI), frailty,
      presence of cancer, nutritional status, wound class, preoperative functional
      status, and surgical approach. RESULTS: Hundred and forty-nine patients (79 men
      and 70 women) were included in the analysis. Mean age was 77.7 +/- 4.9 years,
      mean BMI was 27.2 +/- 5.5 kg/m(2), and the median CCI was 3 (IQR 2-6). The mean
      preoperative SPPB score was 9.62 +/- 2.33. A total of 52 patients (34.9 %)
      experienced one or more postoperative complications, including four mortalities,
      and a total of 72 complications. The mean comprehensive complication index score
      for these patients was 25.7 +/- 23.8. In the presence of all other variables
      included in the model, a higher comprehensive complication index score was found
      to significantly decrease the hazard of recovery (HR 0.96, CI 0.94-0.98, p value
      = 0.0004) and hence increase the time to recovery. CONCLUSION: Following elective
      abdominal surgery, elderly patients who experience a greater number and more
      severe postoperative complications take longer to return to their preoperative
      functional status.

PMID- 26194261
TI  - A systematic review of the effect of distraction on surgeon performance:
      directions for operating room policy and surgical training.
AB  - BACKGROUND: Distractions during surgical procedures have been linked to medical
      error and team inefficiency. This systematic review identifies the most common
      and most significant forms of distraction in order to devise guidelines for
      mitigating the effects of distractions in the OR. METHODS: In January 2015, a
      PubMed and Google Scholar search yielded 963 articles, of which 17 (2 %) either
      directly observed the occurrence of distractions in operating rooms or conducted
      a laboratory experiment to determine the effect of distraction on surgical
      performance. RESULTS: Observational studies indicated that movement and case
      irrelevant conversation were the most frequently occurring distractions, but
      equipment and procedural distractions were the most severe. Laboratory studies
      indicated that (1) auditory and mental distractions can significantly impact
      surgical performance, but visual distractions do not incur the same level of
      effects; (2) task difficulty has an interaction effect with distractions; and (3)
      inexperienced subjects reduce their speed when faced with distractions, while
      experienced subjects did not. CONCLUSION: This systematic review suggests that
      operating room protocols should ensure that distractions from intermittent
      auditory and mental distractions are significantly reduced. In addition, surgical
      residents would benefit from training for intermittent auditory and mental
      distractions in order to develop automaticity and high skill performance during
      distractions, particularly during more difficult surgical tasks. It is unclear as
      to whether training should be done in the presence of distractions or
      distractions should only be used for post-training testing of levels of
      automaticity.

PMID- 26194262
TI  - Trans-oral cricomyotomy using a flexible endoscope: technique and clinical
      outcomes.
AB  - INTRODUCTION: Zenker's diverticulum (ZD) is a rare upper esophageal pathology
      that is most prevalent in the sixth and seventh decade. Three different
      therapeutical options are available: (1) open trans-cervical approach, (2) rigid
      endoscopy and (3) flexible endoscopy. Our hypothesis is that a flexible
      endoscopic cricomyotomy represents a safe and effective treatment of ZD as well
      as cricopharyngeal spasm. METHODS: A retrospective analysis of all patients that
      underwent a flexible endoscopic cricomyotomy at our institution between October
      2008 and May 2014 was performed. Preoperative and postoperative (1 month and long
      term follow-up) symptom scores and clinical outcomes were collected. Briefly, the
      ZD is carefully identified endoscopically and the common wall is divided using
      needle knife cautery with the help of an endoscopic cap. Clips are used to close
      the mucosal defect starting with the apex. RESULTS: Twenty-six patients underwent
      a flexible endoscopic myotomy for a ZD. Of 26 patients, five (19.2 %) had a
      history of previous open or stapled trans-oral myotomy and four (15.4 %)
      underwent a concomitant foregut procedure. Mean length of stay was 1.5 days
      (range 1-11). Mean operative time was 68 min (range 28-149). One patient
      presented with a postoperative leak, and one patient presented with a retained
      clip. Both were treated endoscopically. Recurrent weekly dysphagia was present in
      3/26 (11.5 %). One patient (3.8 %) underwent an endoscopic bougie dilatation
      postoperatively. With regard to clinical outcomes, there was a statistically
      significant improvement in both short-term (1 month) and long-term (median follow
      up 21.8 months; range 1-68.2 months) dysphagia (p < 0.001; p < 0.001),
      regurgitation (p = 0.001; p = 0.017), cough (p = 0.006; p = 0.025) and aspiration
      (p = 0.013; p = 0.013). CONCLUSION: Flexible endoscopic cricomyotomy offers
      durable relief of dysphagia, regurgitation, cough and aspiration in ZD patients.
      It appears to have a good safety profile with symptomatic recurrence occurring in
      up to 11.5 % of cases.

PMID- 26194263
TI  - Paraesophageal hernia repair in the emergency setting: is laparoscopy with the
      addition of a fundoplication the new gold standard?
AB  - BACKGROUND: Laparoscopic repair of paraesophageal hernia (PEH) with
      fundoplication is currently the preferred elective strategy, but emergent cases
      are often done open without an anti-reflux (AR) procedure. This study examined
      PEH repair in elective and urgent/emergent settings and investigated patient
      characteristic influence on the use of adjunctive techniques, such as AR
      procedures or gastrostomy tube (GT) placement. METHODS: Utilizing the University
      HealthSystem Consortium Clinical Database Resource Manager, selected discharge
      data were retrieved using International Classification of Disease 9 diagnosis
      codes for PEH and procedure specific codes. Chi-squared and paired t tests were
      applied (alpha = 0.05). RESULTS: Discharge data from October 2010 through June
      2014 indicated 7950 patients (>=18 years) underwent PEH surgery, 84.7 % were
      performed laparoscopically and 15.3 % open. 24.6 % of cases were classified
      urgent/emergent upon admission, and almost 70 % of these were completed
      laparoscopically. Open paraesophageal hernia repairs (OHR) represented a higher
      proportion of urgent/emergent cases but were only 30 % of this total.
      Laparoscopic paraesophageal hernia repair (LHR) patients were more likely to
      receive an AR procedure in all situations (54.9 % LHR vs. 26.3 % OHR). Almost 90
      % of elective PEH repairs in this cohort were laparoscopic. Elective cases were
      more commonly associated with AR procedures than emergent cases which frequently
      incorporated GT placement. CONCLUSION: We demonstrate that laparoscopic PEH
      repair has become accepted in emergent cases. Open PEH repair is often reserved
      for emergent surgeries and less commonly includes an AR procedure. Laparoscopy
      with an AR procedure is clearly the standard of care in elective surgery. The
      decision to perform an open or laparoscopic surgery, with or without adjunctive
      techniques, may be based more on the physician's comfort with laparoscopic
      surgery and surgical practices than the patient's condition. Long-term follow-up
      studies are needed to determine the functional outcomes of these strategies.

PMID- 26194264
TI  - Fluorocholangiography: reincarnation in the laparoscopic era-evaluation of intra
      operative cholangiography in 3635 laparoscopic cholecystectomies.
AB  - BACKGROUND: The introduction of laparoscopic cholecystectomy (LC) resulted in the
      decline of routine intra-operative cholangiography (IOC). Common bile duct stones
      are being diagnosed preoperatively using magnetic resonance
      cholangiopancreatography (MRCP). We aim to evaluate the use and benefits of IOC
      during laparoscopic biliary surgery at a high-volume biliary surgery unit.
      METHODS: Prospective data from 4088 patients undergoing LC over 22 years were
      analysed. Referral protocols allow one firm to receive the great majority of
      biliary emergencies and all suspected ductal stones. All patients with gall
      stones on ultrasound scanning, fit for surgery, will undergo LC during the index
      admission. MRCP and ERCP are not part of preoperative investigation. A four-port
      LC is performed with a size 5Fr ureteric catheter within an open cannula to
      obtain an IOC through right sub-costal port. RESULTS: Of 4088 patients, IOC was
      attempted in 3691 (90.2 %) and 3635 had a successful IOC (98.4 %). 75 % were
      females. The mean age was 59 years. Patients presented with one or more of the
      following: chronic biliary pain in 60 %, acute pain 26.7 %, acute cholecystitis
      8.4 %, gallstone pancreatitis 7.8 % and jaundice with or without cholangitis in
      19.2 %. A total of 1328 patients (36.5 %) had risk factors for CBD stones. The
      IOC was abnormal in 975 cases (26.8 %), recording 1599 abnormalities. IOC
      identified 774 patients with CBD stones (21.3 %), including previously
      unsuspected CBD stones in 4.7 %. IOC was false negative in 20 cases (0.5 %) found
      to have stones on basket exploration. A decision not to perform IOC in 453 cases
      (11 %) was made preoperatively in 74.2 % and intra-operatively in 12.3 %.
      CONCLUSION: IOC can be safely and routinely performed in LC. It helps to identify
      CBD stones, even in patients with no known risk factors, delineate bile duct
      anatomy and facilitate single-stage management of CBD stones.

PMID- 26194265
TI  - Laparoscopic sleeve gastrectomy with 27 versus 39 Fr bougie calibration: a
      randomized controlled trial.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a widely used
      primary bariatric surgery. As this is a restrictive procedure, calibrating bougie
      size is assumed to impact on both morbidity and weight loss. However, no
      prospective studies have confirmed this hypothesis. The objective of this trial
      was to compare LSG outcomes using different calibrating bougie diameters.
      MATERIALS AND METHODS: A randomized controlled trial: 126 patients undergoing LSG
      were randomized to either a 27-Fr (group A) or a 39-Fr (group B) calibrating
      bougie. Inclusion criteria were BMI 40-50 kg/m(2), aged 20-70 and absence of
      prior gastric surgery. All surgeries were performed by the same surgeon. Sample
      size was calculated to detect a six-point difference in percentage of excess
      weight loss (%EWL) at 1 year after surgery, considering an alpha error = 0.05 and
      a beta error = 0.2. The volume of resected stomach, morbidity and weight loss at
      6 months and at 1 year after surgery were analyzed. RESULTS: Groups (group A n =
      62, group B n = 64) were similar in BMI (44.3 vs. 43.5), aged (41.9 vs. 42.2) and
      female percentage (87.1 vs. 84.3 %). A 1-year follow-up was achieved in 90.1 and
      87.1 %, respectively. Two major complications occurred, one leak in each group
      (1.6 %). The volume of resected stomach was similar (426 vs. 402 ml, P = 0.71),
      as well as 6 months %EWL (66.3 vs. 66.6 %; P = 0.91) and 1 year %EWL (75.6 vs.
      71.3 %, P = 0.21). A 1-year %EWL higher than 50 was achieved in 96.5 % of
      patients in group A versus 85.2 % in group B (P = 0.11). CONCLUSIONS: The use of
      different bougie diameters had no impact on the volume of resected stomach,
      morbidity or short-term weight loss after LSG, although a trend was seen toward
      better weight loss with the smaller bougie. A longer-lasting follow-up will be
      necessary to further assess differences.

PMID- 26194266
TI  - Gender differences in patients undergoing surgery for acute type A aortic
      dissection: Is there really a glass ceiling?

PMID- 26194267
TI  - Bilateral weighted radiographs are required for accurate classification of
      acromioclavicular separation: an observational study of 59 cases.
AB  - INTRODUCTION: Misinterpretation of the Rockwood classification system for
      acromioclavicular joint (ACJ) separations has resulted in a trend towards using
      unilateral radiographs for grading. Further, the use of weighted views to
      'unmask' a grade III injury has fallen out of favour. Recent evidence suggests
      that many radiographic grade III injuries represent only a partial injury to the
      stabilising ligaments. This study aimed to determine (1) whether accurate
      classification is possible on unilateral radiographs and (2) the efficacy of
      weighted bilateral radiographs in unmasking higher-grade injuries. METHODS:
      Complete bilateral non-weighted and weighted sets of radiographs for patients
      presenting with an acromioclavicular separation over a 10-year period were
      analysed retrospectively, and they were graded I-VI according to Rockwood's
      criteria. Comparison was made between grading based on (1) a single antero
      posterior (AP) view of the injured side, (2) bilateral non-weighted views and (3)
      bilateral weighted views. Radiographic measurements for cases that changed grade
      after weighted views were statistically compared to see if this could have been
      predicted beforehand. RESULTS: Fifty-nine sets of radiographs on 59 patients (48
      male, mean age of 33 years) were included. Compared with unilateral radiographs,
      non-weighted bilateral comparison films resulted in a grade change for 44
      patients (74.5%). Twenty-eight of 56 patients initially graded as I, II or III
      were upgraded to grade V and two of three initial grade V patients were
      downgraded to grade III. The addition of a weighted view further upgraded 10
      patients to grade V. No grade II injury was changed to grade III and no injury of
      any severity was downgraded by a weighted view. Grade III injuries upgraded on
      weighted views had a significantly greater baseline median percentage
      coracoclavicular distance increase than those that were not upgraded (80.7% vs.
      55.4%, p=0.015). However, no cut-off point for this value could be identified to
      predict an upgrade. CONCLUSIONS: The accurate classification of ACJ separation
      requires weighted bilateral comparative views. Attempts to predict grade on a
      single AP radiograph result in a gross underestimation of severity. The value of
      bilateral weighted views is to 'unmask' a grade V injury, and it is recommended
      as a first-line investigation.

PMID- 26194268
TI  - Severity and treatment of "occult" intra-abdominal injuries in blunt trauma
      victims.
AB  - BACKGROUND: to assess the severity and treatment of "occult" intra-abdominal
      injuries in blunt trauma victims. METHOD: Retrospective analysis of charts and
      trauma register data of adult blunt trauma victims, admitted without abdominal
      pain or alterations in the abdominal physical examination, but were subsequently
      diagnosed with intra-abdominal injuries, in a period of 2 years. The severity was
      stratified according to RTS, AIS, OIS and ISS. The specific treatment for
      abdominal injuries and the complications related to them were assessed. RESULTS:
      Intra-abdominal injuries were diagnosed in 220 (3.8%) out of the 5785 blunt
      trauma victims and 76 (34.5%) met the inclusion criteria. The RTS and ISS median
      (lower quartile, upper quartile) were 7.84 (6.05, 7.84) and 25 (16, 34). Sixty
      seven percent had a GCS>=13 on admission. Injuries were identified in the spleen
      (34), liver (33), kidneys (9), intestines (4), diaphragm (3), bladder (3) and
      iliac vessels (1). Abdominal injuries scored AIS>=3 in 67% of patients. Twenty
      one patients (28%) underwent laparotomy, 5 of which were nontherapeutic. The
      surgical procedures performed were splenectomy (8), suturing of the diaphragm
      (3), intestines (3), bladder (2), kidneys (1), enterectomy/anastomosis (1),
      ligation of the common iliac vein (1), and revascularization of the common iliac
      artery (1). Angiography and embolization of liver and/or spleen injuries were
      performed in 3 cases. Three patients developed abdominal complications, all of
      which were operatively treated. There were no deaths directly related to the
      abdominal injuries. CONCLUSION: Severe "occult" intra-abdominal injuries,
      requiring specific treatment, may be present in adult blunt trauma patients.

PMID- 26194269
TI  - Constructing populations in biobanking.
AB  - This article poses the question of whether biobanking practices and standards are
      giving rise to the construction of populations from which various biobanking
      initiatives increasingly draw on for legitimacy? We argue that although recent
      biobanking policies encourage various forms of engagement with publics to ensure
      legitimacy, different biobanks conceptualize their engagement strategies very
      differently. We suggest that biobanks undertake a broad range of different
      strategies with regard to engagement. We argue that these different approaches to
      engagement strategies are contributing to the construction of populations,
      whereby specific nationalities, communities, societies, patient groups and
      political systems become imbued or bio-objectified with particular
      characteristics, such as compliant, distant, positive, commercialized or
      authoritarian. This bio-objectification process is problematic in relation to
      policy aspirations ascribed to biobanking engagement since it gives rise to
      reified notions of different populations. 

PMID- 26194271
TI  - Change of maternal thyroid function in twin-twin transfusion syndrome.
AB  - Human chorionic gonadotropin (hCG) has weak thyroid-stimulating activity because
      of its homology with thyroid stimulating hormone (TSH). In twin-twin transfusion
      syndrome (TTTS), which is a severe complication of monochorionic twin
      pregnancies, a close association between maternal serum hCG concentration and
      TTTS has been reported. And, TTTS can be treated by fetoscopic laser coagulation
      of the communicating vessels. To clarify the relationship between maternal serum
      hCG and maternal thyroid function in TTTS, the present study investigated the
      change in thyroid hormone and hCG levels after laser therapy. The protocol
      included collection of serial maternal blood samples in TTTS before laser
      therapy, and at two and four weeks after laser therapy. For 131 cases of TTTS,
      the following parameters were determined at each point: hCG, TSH, free
      triiodothyronine (fT3), and free thyroxine (fT4). The multiple of the median
      (MoM) of pre-operative hCG concentration in TTTS was 5.39 MoM (interquartile
      range, 2.83 - 8.64). There was a moderate positive correlation between hCG and
      fT3 in TTTS pre-operatively (R = 0.22, P = 0.030). fT4 was also positively
      correlated with hCG (R = 0.33, P < 0.001). Some cases showed very high
      concentration in fT3. When laser therapy for TTTS was effective, the hCG
      concentration significantly decreased, and fT3 and fT4 decreased progressively in
      concert with the decrease in hCG. The relationship between hCG and thyroid
      function in TTTS supports the finding of TTTS as a novel etiology of hCG-mediated
      hyperthyroidism during pregnancy. 

PMID- 26194270
TI  - The role of outcome expectancies for a training program consisting of meditation,
      breathing exercises, and cold exposure on the response to endotoxin
      administration: a proof-of-principle study.
AB  - Expectancies play a major role for the treatment outcome of a broad variety of
      immune-mediated conditions and may strengthen or mimic the effects of regular
      long-term therapies. This study adds to a recently published study of Kox et al.
      (PNAS 111:7379-7384, 2014) on the ability to voluntarily influence the
      physiological stress response in healthy men after a training program consisting
      of meditation, breathing techniques, and exposure to cold, which found highly
      promising results on the clinical, autonomic, and immune response to
      experimentally induced inflammation (using the experimental human endotoxemia
      model). Within this project, a number of variables were included to assess the
      role of generalized (optimism, neuroticism) and specific outcome expectancies
      (related to the effects of the training on health) on the response to endotoxin
      administration after training. Indications were found that especially the
      generalized outcome expectancy optimism is a potential determinant of the
      autonomic (epinephrine: rho = 0.76, p < .01) and immune response (interleukin-10:
      rho = 0.60, p < .05) to induced inflammation after training, whereas more
      specific expectations with regard to the effects of the training could be
      especially relevant for the clinical symptom report (flu-like symptoms: rho = 
      0.71, p < .01). This proof-of-principle study provides first indications for
      potential innovative treatments to change immune-modulating responses by means of
      psychological mechanisms. If replicated, these findings may be used for
      predicting training responses and potentiate their effects by means of optimism
      inducing interventions in patients with immune-mediated rheumatic conditions. 

PMID- 26194272
TI  - Improvement of beta-cell function ameliorated glycemic variability in patients
      with newly diagnosed type 2 diabetes after short-term continuous subcutaneous
      insulin infusion or in combination with sitagliptin treatment: a randomized
      control trial.
AB  - Glycemic variability (GV) has been proposed as contributor to diabetes-related
      macrovascular complications. This randomized control trial evaluated a new
      combination therapy with continuous subcutaneous insulin infusion (CSII) plus
      sitagliptin (CSII + sitagliptin) vs. CSII only in terms of metabolic control, GV
      and beta-cell function in patients with newly diagnosed type 2 diabetes (T2DM).
      217 patients were randomized to two weeks of CSII (n = 108) or CSII + sitagliptin
      (n = 109) therapy. As a measure of GV, the coefficient of variation (CV) was
      computed from capillary blood glucose during the first and second week,
      respectively. beta-cell function before and after treatment was determined with
      the Insulin Secretion-Sensitivity Index-2 (ISSI-2). Good metabolic controls were
      established with both therapies. CSII + sitagliptin therapy resulted in greater
      improvements in CV and ISSI-2 than CSII alone (all P = 0.000). For each group,
      change in CV was inversely correlated with change in ISSI-2 (r = -0.529, P =
      0.000 and r = -0.433, P = 0.000, respectively). The multivariate regression
      analysis demonstrated that improved ISSI-2 was the only independent contributor
      to reduced CV in both groups (standardized beta = -0.388, P = 0.004 and
      standardized beta = -0.472, P = 0.000, respectively). Correction of beta-cell
      function in newly diagnosed T2DM patients via use of either CSII or CSII +
      sitagliptin therapy was feasible in controlling GV to prevent secondary
      complications of T2DM. Moreover, CSII + sitagliptin therapy was superior to CSII
      monotherapy in terms of GV.

PMID- 26194273
TI  - Low threshold optical bistability at terahertz frequencies with graphene surface
      plasmons.
AB  - We propose a modified Kretschmann-Raether configuration to realize the low
      threshold optical bistable devices at the terahertz frequencies. The metal layer
      is replaced by the dielectric sandwich structure with the insertion of graphene,
      and this configuration can support TM-polarization surface electromagnetic wave.
      The surface plasmon resonance is strongly dependent on the Fermi-level of
      graphene and the thickness of the sandwich structure. It is found that the
      switching-up and switching-down intensities required to observe the optical
      bistable behavior are lowered markedly due to the excitation of the graphene
      surface plasmons, thus making this configuration a prime candidate for
      experimental investigation at the terahertz range. And the switching threshold
      value can be further reduced by decreasing the Fermi-level or increasing the
      thickness of sandwich structure, hence providing a new way for realizing tunable
      optical bistable devices. Finally, the optical bistability at higher terahertz
      frequency and the influence of relaxation time under the actual experimental
      condition on Fermi-level are discussed. 

PMID- 26194274
TI  - The geography of sex-specific selection, local adaptation, and sexual dimorphism.
AB  - Local adaptation and sexual dimorphism are iconic evolutionary scenarios of
      intraspecific adaptive differentiation in the face of gene flow. Although theory
      has traditionally considered local adaptation and sexual dimorphism as
      conceptually distinct processes, emerging data suggest that they often act
      concurrently during evolutionary diversification. Here, I merge theories of local
      adaptation in space and sex-specific adaptation over time, and show that their
      confluence yields several new predictions about the roles of context-specific
      selection, migration, and genetic correlations, in adaptive diversification. I
      specifically revisit two influential predictions from classical studies of clinal
      adaptation and sexual dimorphism: (1) that local adaptation should decrease with
      distance from the species' range center and (2) that opposing directional
      selection between the sexes (sexual antagonism) should inevitably accompany the
      evolution of sexual dimorphism. I show that both predictions can break down under
      clinally varying selection. First, the geography of local adaptation can be
      sexually dimorphic, with locations of relatively high local adaptation differing
      profoundly between the sexes. Second, the intensity of sexual antagonism varies
      across the species' range, with subpopulations near the range center representing
      hotspots for antagonistic selection. The results highlight the context-dependent
      roles of migration versus sexual conflict as primary constraints to adaptive
      diversification. 

PMID- 26194275
TI  - Balancing family life with a science career.

PMID- 26194276
TI  - DPP4 in anti-tumor immunity: going beyond the enzyme.

PMID- 26194277
TI  - XBP1, a determinant of the eosinophil lineage.

PMID- 26194278
TI  - NLRP3 moonlights in TH2 polarization.

PMID- 26194279
TI  - Tuning up FALCs: immunological shielding in the body cavities.

PMID- 26194287
TI  - Erratum: TET1 is a tumor suppressor of hematopoietic malignancy.

PMID- 26194288
TI  - Erratum: The diverse role of RIP kinases in necroptosis and inflammation.

PMID- 26194286
TI  - Guarding the frontiers: the biology of type III interferons.
AB  - Type III interferons (IFNs) or IFN-lambdas regulate a similar set of genes as
      type I IFNs, but whereas type I IFNs act globally, IFN-lambdas primarily target
      mucosal epithelial cells and protect them against the frequent viral attacks that
      are typical for barrier tissues. IFN-lambdas thereby help to maintain healthy
      mucosal surfaces through immune protection, without the significant immune
      related pathogenic risk associated with type I IFN responses. Type III IFNs also
      target the human liver, with dual effects: they induce an antiviral state in
      hepatocytes, but specific IFN-lambda4 action impairs the clearance of hepatitis C
      virus and could influence inflammatory responses. This constitutes a paradox that
      has yet to be resolved. 

PMID- 26194289
TI  - Multiparametric MRI Improves Accuracy of Clinical Nomograms for Predicting
      Extracapsular Extension of Prostate Cancer.
AB  - OBJECTIVE: To compare the accuracy of multiparametric magnetic resonance imaging
      (MP-MRI) with the Partin tables and Memorial Sloan-Kettering (MSK) nomogram for
      predicting extracapsular extension (ECE) in prostate cancer and to create a tool
      for clinicians to estimate pathologic ECE risk. METHODS: A retrospective review
      of 112 patients who underwent 3T MP-MRI of the prostate and radical prostatectomy
      was performed. Regression analyses were carried out to identify predictors of
      ECE. Predictive accuracy of models based on nomogram and MP-MRI were compared.
      RESULTS: A total of 33 of patients (29%) had ECE on MP-MRI whereas 26 patients
      (23%) had ECE on final pathology. Mean age was 62.8 years and mean prostate
      specific antigen was 8.2 ng/dL. MRI was a significant predictor of ECE that was
      independent of age, prostate-specific antigen, Gleason score, clinical stage, and
      percent positive cores on biopsy. Sensitivity, specificity, positive predictive
      value, and negative predictive value of MP-MRI for ECE were 84.6%, 87.2%, 66.7%,
      and 94.9%, respectively. Areas under the curve for Partin and MSK nomograms for
      predicting ECE were 0.85 and 0.86, respectively. Area under the curve increased
      to 0.92 and 0.94, respectively, when MP-MRI was added to each nomogram. We
      provide an online tool that integrates Partin or MSK nomogram results with ECE
      status determined from MRI to predict pathologic ECE. Within the typical range of
      risks for ECE provided by the clinical nomograms (ie, 15%-40%), MRI was useful
      for predicting pathologic ECE. CONCLUSION: MP-MRI may be a useful adjunct for
      clinically staging prostate cancer. MP-MRI improved accuracy of existing clinical
      nomograms for prediction of pathologic ECE.

PMID- 26194290
TI  - Prevalence of Hydronephrosis in Women With Advanced Pelvic Organ Prolapse.
AB  - OBJECTIVE: To describe the prevalence of hydronephrosis in advanced pelvic organ
      prolapse (POP) and to describe clinical and urodynamic parameters associated with
      hydronephrosis. MATERIALS AND METHODS: Prospective, observational cohort study
      examining the prevalence of hydronephrosis in advanced POP. Women with a POP-Q
      examination of at least +1 for points C, Aa, or Ba were enrolled and screened for
      hydronephrosis. Basic demographics, clinical, and urodynamic findings among women
      with and without hydronephrosis were compared. The University of Southern
      California IRB approved this protocol. RESULTS: A total of 180 participants were
      enrolled. Fifty-five women had some hydronephrosis, for a prevalence of 30.6%
      (24.3%-37.6%). Mean age was 57.9 (+/-9.0) years and mean body mass index was 29.2
      kg/m(2) (+/- 4.6). Of the participants, 80.6% were postmenopausal. The presence
      of diabetes mellitus was significantly associated with hydronephrosis (8% without
      vs 21.8% with, P = .009), as was the degree of anterior and apical (median Aa,
      Ba, C, and D higher with hydronephrosis than without, P <.01) but not posterior
      POP (median Ap and Bp, P = .13, and .2, respectively). On multichannel
      urodynamics, participants with hydronephrosis had higher mean post void residuals
      (64.8 vs 38.5 mL, P = .007), lower mean first leak (199.6 vs 280.8 mL, P = .006),
      and higher mean maximum cystometric capacity (525.2 vs 476.7 mL, P = .02)
      compared with participants without hydronephrosis. CONCLUSION: The prevalence of
      hydronephrosis in women with advanced POP is 30.6%. Clinical factors associated
      with hydronephrosis include degree of anterior or apical POP and diabetes
      mellitus. Urodynamic factors associated with hydronephrosis include elevated
      postvoid residuals, larger cystometric capacity, and lower volume at first leak.

PMID- 26194291
TI  - Editorial Comment.

PMID- 26194292
TI  - Congenital Aphallia: Review of Pathogenesis and Current Treatment Guidelines.
AB  - Congenital aphallia is an extremely rare disorder with <100 cases reported
      globally. We report on an 11-month-old infant with aphallia and associated syrinx
      formation. We also review the pathogenesis, associated malformations, and current
      treatment guidelines for penile agenesis. 

PMID- 26194293
TI  - Associate Editor for Review Articles: Dr. Fred Saad.

PMID- 26194294
TI  - Patients With Prostatic Inflammation Undergoing Transurethral Prostatic Resection
      Have a Larger Early Improvement of Storage Symptoms.
AB  - OBJECTIVE: To evaluate the association between prostate inflammation, metabolic
      syndrome (MetS), and postoperative lower urinary tract symptoms in patients
      treated with transurethral resection of the prostate (TURP). METHODS: From April
      2011, a consecutive series of patients treated with TURP were prospectively
      included in this observational study. MetS was defined according to the National
      Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria.
      Patients were evaluated at baseline and 1 month postoperative with the
      International Prostate Symptom Score (IPSS), including the storage IPSS (sIPSS)
      and voiding IPSS (vIPSS) subscores, the Overactive Bladder questionnaire (OAB-q),
      and uroflowmetry. Prostate volume was evaluated at baseline. Complications were
      classified using the modified Clavien system. TURP specimens were examined to
      define grade, location, and extent of the inflammatory infiltrate according to
      the standardized classification system of chronic prostatitis and/or chronic
      pelvic pain syndrome. RESULTS: One hundred and thirty-one subjects were enrolled,
      in which 54 patients (41.3%) presented with MetS. No differences were observed in
      terms of preoperative prostate-specific antigen, OAB score, IPSS, vIPSS, sIPSS,
      Qmax, post void residual, and prostate volume in subjects with and without MetS.
      An incidence of postoperative complications of 10.6% was recorded: 79% were
      classified as Clavien type I or II; 21% Clavien IIIb. Of 131 subjects, 97 (74.1%)
      presented with an inflammatory infiltrate. Patients with MetS presented a high
      proportion of inflammatory infiltrates compared to patients without MetS (45 of
      54; 83% vs 52 of 77; 67%, P = .01). Patients with prostate inflammation presented
      a 50% risk reduction of postoperative storage urinary symptoms. CONCLUSION: We
      confirmed the association between MetS and prostate inflammation.Patients with
      inflammatory infiltrates mostly benefit from TURP, particularly regarding storage
      symptoms.

PMID- 26194295
TI  - Postprostatectomy Anastomosis Stenosis: A Systematic Review.
AB  - Anastomotic strictures (AS) are uncommon but a vexing problem after radical
      prostatectomy. We reviewed the literature for AS treatment modalities to
      summarize the best management strategies for AS, as supported by current
      evidence. Twenty studies fit the inclusion and exclusion criteria. Weighted
      success rates and incontinence rates were calculated and used to create a
      treatment algorithm. Repeat attempts of minimally invasive methods seem to
      improve the success rate. Repeat procedures and more invasive techniques,
      however, may lead to higher incontinence rates. 

PMID- 26194296
TI  - Robot-assisted Laparoscopic Repair of Vesicovaginal Fistula: A Single-center
      Experience.
AB  - OBJECTIVE: To describe our surgical technique and outcomes with robot-assisted
      laparoscopic repair of vesicovaginal fistula (VVF) in 10 patients. METHODS: From
      November 2010 to April 2014, a total of 10 patients with VVF underwent robot
      assisted laparoscopic VVF repair. The principles of VVF repair were followed. The
      fistula tract was excised. The vagina defect and the cystotomy were closed with a
      flap of epiploica of sigmoid colon, a peritoneal inlay, or a bladder adventitia
      layer interposed between the bladder and vaginal suture lines. Perioperative
      patient characteristics, complications, operative data, and follow-up results
      were retrospectively reviewed with institutional review board approval. RESULTS:
      All 10 patients developed VVF as a result of previous elective hysterectomies for
      benign indications. Mean operative time was 214 minutes (range, 120-457 minutes).
      Longer operative times were caused by concomitant surgeries (3 ureteral
      reimplantations and 1 planned sigmoid colectomy). Median length of stay was 1 day
      (range, 1-5 days). There were no intraoperative complications. Perioperatively,
      there was 1 Clavien-Dindo grade 1 complication (ileus), and 2 grade 2
      complications (readmission with Clostridium difficile infection and atelectasis).
      All patients were cured and were without VVF recurrence at a median follow-up
      close to 2 years. CONCLUSION: Robot-assisted laparoscopic VVF repair is an
      effective approach to manage VVF even in complex medical scenarios. It is
      anticipated that an increasing number of VVF repairs will be undertaken with
      robot-assisted approach in the future, offering more patients who need VVF repair
      the advantages of minimally invasive surgery.

PMID- 26194297
TI  - Editorial Comment.

PMID- 26194298
TI  - Editorial Comment.

PMID- 26194299
TI  - Reply: To PMID 26194291.

PMID- 26194300
TI  - Elucidation of the Pattern of the Onset of Male Lower Urinary Tract Symptoms
      Using Cluster Analysis: Efficacy of Tamsulosin in Each Symptom Group.
AB  - OBJECTIVE: To present a new grouping of male patients with lower urinary tract
      symptoms (LUTS) based on symptom patterns and clarify whether the therapeutic
      effect of alpha1-blocker differs among the groups. METHODS: We performed
      secondary analysis of anonymous data from 4815 patients enrolled in a
      postmarketing surveillance study of tamsulosin in Japan. Data on 7 International
      Prostate Symptom Score (IPSS) items at the initial visit were used in the cluster
      analysis. IPSS and quality of life (QOL) scores before and after tamsulosin
      treatment for 12 weeks were assessed in each cluster. Partial correlation
      coefficients were also obtained for IPSS and QOL scores based on changes before
      and after treatment. RESULTS: Five symptom groups were identified by cluster
      analysis of IPSS. On their symptom profile, each cluster was labeled as minimal
      type (cluster 1), multiple severe type (cluster 2), weak stream type (cluster 3),
      storage type (cluster 4), and voiding type (cluster 5). Prevalence and the mean
      symptom score were significantly improved in almost all symptoms in all clusters
      by tamsulosin treatment. Nocturia and weak stream had the strongest effect on QOL
      in clusters 1, 2, and 4 and clusters 3 and 5, respectively. CONCLUSION: The study
      clarified that 5 characteristic symptom patterns exist by cluster analysis of
      IPSS in male patients with LUTS. Tamsulosin improved various symptoms and QOL in
      each symptom group. The study reports many male patients with LUTS being
      satisfied with monotherapy using tamsulosin and suggests the usefulness of alpha1
      blockers as a drug of first choice.

PMID- 26194301
TI  - The Utility of the Remnant Kidney Volume/Body Surface Area Ratio and Tumor
      Diameter as Predictors of Postoperative Degree of Renal Functional Decline in
      Patients With Renal Cell Carcinoma Treated by Radical Nephrectomy.
AB  - OBJECTIVE: To characterize the preoperative factors affecting renal cell
      carcinoma patients as predictive of post-radical nephrectomy (RN) mild (M
      decline) or severe (S-decline) renal functional decline and to elucidate the
      histopathologic features of the resected normal kidney cortex, as well as the
      occurrence of cardiovascular disease (CVD) in both M-decline and S-decline
      patients. MATERIALS AND METHODS: M-decline and S-decline were categorized as a
      percentage of postoperative estimated glomerular filtration rate decline of <20
      and of >40, respectively. The preoperative factors analyzed were patient
      demographics, comorbidities, and radiographic findings, including remnant kidney
      status and tumor size. The factors based on postoperative information analyzed
      were tumor and normal cortex pathology and CVD events. RESULTS: In 175 patient
      cohort, 21 and 32 cases were categorized as M-decline and S-decline,
      respectively. Absence of comorbidities, larger remnant kidney volume (RKV)/body
      surface area (BSA) ratio, and larger tumor diameter were significantly predictive
      of M-decline, whereas smaller tumor diameter was significantly predictive of S
      decline. The global glomerulosclerosis extent in nephrectomized normal cortex of
      S-decline cases was significantly higher than in other types of cases. No CVD
      event was observed in M-decline cases. CONCLUSION: This is the first report to
      identify the RKV/BSA ratio as a promising predictor of post-RN degree of renal
      functional decline. Post-RN prevention of life-threatening outcomes according to
      preoperative and postoperative information, including the degree of post-RN renal
      functional decline and histopathology of the nephrectomized normal cortex, should
      be considerable in future urological tasks.

PMID- 26194302
TI  - Reply: To PMID 26194296.

PMID- 26194303
TI  - Mercury in Forage Fish from Mexico and Central America: Implications for Fish
      Eating Birds.
AB  - Mercury (Hg) is a global contaminant of aquatic food chains. Aquatic birds, such
      as the osprey (Pandion haliaetus), with migratory populations breeding in Canada
      and the northern United States and wintering in the Central and South America,
      can be exposed to mercury on both the breeding and wintering ranges. We examined
      Hg levels in 14 fish taxa from 24 osprey wintering sites identified from
      satellite telemetry. Our main goal was to determine whether fish species that
      feature in the diet of overwintering and resident fish-eating birds reached
      toxicity thresholds for Hg. Mean Hg levels in fish whole carcasses ranged from a
      high of 0.18 ug g(-1) (wet weight) in Scomberomorus sierra to a low of 0.009 ug
      g(-1) in Catostomidae. Average Hg levels were within published toxicity threshold
      values in forage fish for only two sites in Mexico (Puerto Vallarta and San Blas
      Estuary), and all were marine species, such as mackerel (Scomberomorus sierra),
      sea catfish (Ariopus spp.), and sardinas species (Centropomus spp.). Except for
      one sample from Nicaragua, sea catfish from Puerto Morazan, none of the fish from
      sites in Central America had Hg levels which exceeded the thresholds. Nonmetric
      multidimensional scaling revealed geographical differences in Hg levels with
      significant pairwise differences between sites along the Pacific Ocean (Mexico)
      versus the Bay of Campeche, partly due to differences in species composition of
      sampled fish (and species distributions). Hg increased with trophic level, as
      assessed by nitrogen stable isotope ratios (delta(15)N but not delta(13)C), in
      freshwater and marine, but not estuarine, environments. Hg concentrations in
      forage fish do not account for the elevated Hg reported for many osprey
      populations on the breeding grounds, thus primary sources of contamination appear
      to be in the north. 

PMID- 26194304
TI  - Insights into copper effect on Proteus hauseri through proteomic and metabolic
      analyses.
AB  - This is the first-attempt to use liquid chromatography coupled with tandem mass
      (LC-MS-MS) in deciphering the effects of copper ion on Proteus hauseri. Total 941
      proteins in copper-addition (+Cu) group and 898 proteins in non-copper-addition (
      Cu) group were found, which containing 221 and 178 differential proteins in +Cu
      and -Cu group, respectively. Differential proteins in both groups were defined
      into 14 groups by their functional classification which transport/membrane
      function proteins were the major different part between the two groups, which
      took 19.5% and 7.7%, respectively. The result of BioCyc and KEGG analyses on
      metabolic pathway indicated that copper could interrupted the pathway of
      chemotaxis CheY and inhibited the swarming of P. hauseri, which provided a
      potential in controlling the pathogenicity of this strain. 

PMID- 26194305
TI  - Fucoidan from sea cucumber Cucumaria frondosa exhibits anti-hyperglycemic effects
      in insulin resistant mice via activating the PI3K/PKB pathway and GLUT4.
AB  - The present study investigated the anti-hyperglycemic properties and mechanisms
      of fucoidan, isolated from Cucumaria frondosa (Cf-FUC), in insulin resistant
      mice. Male C57BL/6J mice were fed regular diet or high-fat/high-sucrose diet for
      19 weeks. Model animals were dietary administrated either rosiglitazone (RSG, 1
      mg/kg.bw), fucoidan (Cf-FUC, 80 mg/kg.bw) or their combinations. Results showed
      that Cf-FUC significantly reduced fasting blood glucose and insulin levels, and
      enhanced glucose tolerance and insulin tolerance in insulin-resistant mice.
      Quantitative real-time PCR analysis showed that Cf-FUC increased the mRNA
      expressions of insulin receptors (IR), insulin receptor substrate 1 (IRS-1),
      phosphatidylinositol 3 kinase (PI3K), protein kinase B (PKB), and glucose
      transporter 4 (GLUT4). Western blot assays demonstrated that Cf-FUC showed no
      effect on total protein expression but nevertheless enhanced the phosphorylation
      of proteins listed above and increased translocation of GLUT4 to the cell
      membrane. Furthermore, Cf-FUC enhanced the effects of RSG. These results
      indicated that Cf-FUC exhibited significant anti-hyperglycemic effects via
      activating PI3K/PKB pathway and GLUT4 in skeletal muscle and adipose tissue. 

PMID- 26194306
TI  - Discrepancies in Left Ventricular Mass Calculation Based on Echocardiography and
      Cardiovascular Magnetic Resonance Measurements in Patients with Left Ventricular
      Hypertrophy.
AB  - BACKGROUND: Increased left ventricular (LV) mass is associated with adverse
      cardiovascular outcomes, and its accurate assessment is important. The aim of
      this study was to analyze the degree of difference among various methods of LV
      mass calculation based on transthoracic echocardiographic (TTE) measurements and
      cardiovascular magnetic resonance (CMR) measurements, especially in patients with
      aortic stenosis with varying degrees of LV hypertrophy (LVH). The mechanism
      underlying this disagreement was also investigated. METHODS: Ninety-nine patients
      with moderate to severe aortic stenosis and 33 control subjects matched for age,
      sex, body weight, and height were enrolled in this prospective observational
      cohort study. All patients underwent TTE and CMR imaging. LV mass index (LVMI)
      was calculated using three formulas on the basis of TTE measurements (the Penn
      cube, American Society of Echocardiography [ASE], and Teichholz methods) and
      compared with measurements obtained using CMR, the reference method. RESULTS:
      Although all methods calculated using TTE measurements showed good correlations
      with CMR measurements, LVMI measured using the Penn-cube and ASE methods tended
      to be larger than LVMI measured using CMR (difference in LVMI by the Penn-cube
      and ASE methods, 59.3 +/- 29.7 and 30.6 +/- 22.3 g/m2, respectively). This
      tendency decreased with the Teichholz method (difference in LVMI by the Teichholz
      method, 22.9 +/- 19.1 g/m2). The degree of LVMI overestimation was significantly
      different among the three methods (P < .001 by one-way analysis of variance),
      which was more significant in patients with LVH, especially with the Penn-cube
      method (differences between CMR and TTE measurements in patients with aortic
      stenosis and LVH, 66.3 +/- 34.8 vs 31.2 +/- 26.6 vs 15.5 +/- 20.9 g/m2 for the
      Penn-cube, ASE, and Teichholz methods, respectively; P < .001 with post hoc Tukey
      analysis). There was a good correlation between LVMI and LV diameter-to-length
      ratio (r = 0.468, P < .001), which suggested that the left ventricle takes on a
      more globular shape with the increase of LVMI, resulting in a significant
      deviation from the basic assumptions on which the Penn-cube and ASE methods were
      built. CONCLUSIONS: Current methods of calculating LVMI from echocardiographic
      measurements carry a tendency to measure LVMI larger than methods based on CMR
      measurements, which was more significant in patients with LVH. The change of the
      left ventricle's shape with LVH may be a plausible explanation for this, and a
      correction method may be needed when calculating LVMI from echocardiographic
      measurements, especially in patients with LVH and smaller body size.

PMID- 26194307
TI  - Alzheimer's Disease Neuroimaging Initiative: A decade of progress in Alzheimer's
      disease.

PMID- 26194308
TI  - Introduction to special issue: Overview of Alzheimer's Disease Neuroimaging
      Initiative.
AB  - The Alzheimer's Disease Neuroimaging Initiative (ADNI), designed as a
      naturalistic longitudinal study to develop and validate magnetic resonance,
      positron emission tomography, cerebrospinal fluid, and genetic biomarkers for use
      in AD clinical trials, has made many impacts in the decade since its inception.
      The initial 5-year study, ADNI-1, enrolled cognitively normal, mild cognitive
      impairment (MCI) and AD subjects, and the subsequent studies (ADNI-GO and ADNI-2)
      added early- and late-MCI cohorts. The development of standardized methods
      allowed comparison of data gathered across multiple sites, and these data are
      available to qualified researchers without embargo. ADNI data have been used in
      >600 publications including those describing relationships between biomarkers,
      improved methods for disease diagnosis and the prediction of future decline, and
      identifying novel genetic AD risk loci. ADNI has provided a framework for similar
      initiatives worldwide. 

PMID- 26194309
TI  - Alzheimer's Disease Neuroimaging Initiative 2 Clinical Core: Progress and plans.
AB  - INTRODUCTION: This article reviews the current status of the Clinical Core of the
      Alzheimer's Disease Neuroimaging Initiative (ADNI), and summarizes planning for
      the next stage of the project. METHODS: Clinical Core activities and plans were
      synthesized based on discussions among the Core leaders and external advisors.
      RESULTS: The longitudinal data in ADNI-2 provide natural history data on a
      clinical trials population and continue to inform refinement and standardization
      of assessments, models of trajectories, and clinical trial methods that have been
      extended into sporadic preclinical Alzheimer's disease (AD). DISCUSSION: Plans
      for the next phase of the ADNI project include maintaining longitudinal follow-up
      of the normal and mild cognitive impairment cohorts, augmenting specific clinical
      cohorts, and incorporating novel computerized cognitive assessments and patient
      reported outcomes. A major hypothesis is that AD represents a gradually
      progressive disease that can be identified precisely in its long presymptomatic
      phase, during which intervention with potentially disease-modifying agents may be
      most useful.

PMID- 26194311
TI  - The Alzheimer's Disease Neuroimaging Initiative 2 PET Core: 2015.
AB  - INTRODUCTION: This article reviews the work done in the Alzheimer's Disease
      Neuroimaging Initiative positron emission tomography (ADNI PET) core over the
      past 5 years, largely concerning techniques, methods, and results related to
      amyloid imaging in ADNI. METHODS: The PET Core has used [(18)F]florbetapir
      routinely on ADNI participants, with over 1600 scans available for download. Four
      different laboratories are involved in data analysis, and have examined factors
      such as longitudinal florbetapir analysis, use of [(18)F]fluorodeoxyglucose (FDG)
      PET in clinical trials, and relationships between different biomarkers and
      cognition. RESULTS: Converging evidence from the PET Core has indicated that
      cross-sectional and longitudinal florbetapir analyses require different reference
      regions. Studies have also examined the relationship between florbetapir data
      obtained immediately after injection, which reflects perfusion, and FDG-PET
      results. Finally, standardization has included the translation of florbetapir PET
      data to a centiloid scale. CONCLUSION: The PET Core has demonstrated a variety of
      methods for the standardization of biomarkers such as florbetapir PET in a
      multicenter setting.

PMID- 26194310
TI  - Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2.
AB  - INTRODUCTION: Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its
      10th year. The primary objective of the magnetic resonance imaging (MRI) core of
      ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD)
      and related disorders. METHODS: We review the contributions of the MRI core from
      present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also
      review plans for the future-ADNI-3. RESULTS: Contributions of the MRI core
      include creating standardized acquisition protocols and quality control methods;
      examining the effect of technical features of image acquisition and analysis on
      outcome metrics; deriving sample size estimates for future trials based on those
      outcomes; and piloting the potential utility of MR perfusion, diffusion, and
      functional connectivity measures in multicenter clinical trials. DISCUSSION: Over
      the past decade the MRI core of ADNI has fulfilled its mandate of improving
      methods for clinical trials in AD and will continue to do so in the future.

PMID- 26194312
TI  - The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of
      progress and plans.
AB  - INTRODUCTION: We describe Alzheimer's Disease Neuroimaging Initiative (ADNI)
      Biomarker Core progress including: the Biobank; cerebrospinal fluid (CSF) amyloid
      beta (Abeta1-42), t-tau, and p-tau181 analytical performance, definition of
      Alzheimer's disease (AD) profile for plaque, and tangle burden detection and
      increased risk for progression to AD; AD disease heterogeneity; progress in
      standardization; and new studies using ADNI biofluids. METHODS: Review
      publications authored or coauthored by ADNI Biomarker core faculty and selected
      non-ADNI studies to deepen the understanding and interpretation of CSF Abeta1-42,
      t-tau, and p-tau181 data. RESULTS: CSF AD biomarker measurements with the
      qualified AlzBio3 immunoassay detects neuropathologic AD hallmarks in preclinical
      and prodromal disease stages, based on CSF studies in non-ADNI living subjects
      followed by the autopsy confirmation of AD. Collaboration across ADNI cores
      generated the temporal ordering model of AD biomarkers varying across individuals
      because of genetic/environmental factors that increase/decrease resilience to AD
      pathologies. DISCUSSION: Further studies will refine this model and enable the
      use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic
      trials.

PMID- 26194314
TI  - Brain collection, standardized neuropathologic assessment, and comorbidity in
      Alzheimer's Disease Neuroimaging Initiative 2 participants.
AB  - INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative Neuropathology Core
      (ADNI-NPC) facilitates brain donation, ensures standardized neuropathologic
      assessments, and maintains a tissue resource for research. METHODS: The ADNI-NPC
      coordinates with performance sites to promote autopsy consent, facilitate tissue
      collection and autopsy administration, and arrange sample delivery to the NPC,
      for assessment using National Institute on Aging-Alzheimer's Association
      neuropathologic diagnostic criteria. RESULTS: The ADNI-NPC has obtained 45
      participant specimens, and neuropathologic assessments have been completed in 36
      to date. Challenges in obtaining consent at some sites have limited the voluntary
      autopsy rate to 58%. Among assessed cases, clinical diagnostic accuracy for
      Alzheimer disease (AD) is 97%; however, 58% of cases show neuropathologic
      comorbidities. DISCUSSION: Challenges facing autopsy consent and coordination are
      largely resource related. The neuropathologic assessments indicate that ADNI's
      clinical diagnostic accuracy for AD is high; however, many AD cases have
      comorbidities that may impact the clinical presentation, course, and imaging and
      biomarker results. These neuropathologic data permit multimodal and genetic
      studies of these comorbidities to improve diagnosis and provide etiologic
      insights.

PMID- 26194315
TI  - The Alzheimer's Disease Neuroimaging Initiative phase 2: Increasing the length,
      breadth, and depth of our understanding.
AB  - INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a
      multisite study designed to characterize the trajectories of biomarkers across
      the aging process. We present ADNI Biostatistics Core analyses that integrate
      data over the length, breadth, and depth of ADNI. METHODS: Relative progression
      of key imaging, fluid, and clinical measures was assessed. Individuals with
      subjective memory complaints (SMC) and early mild cognitive impairment (eMCI)
      were compared with normal controls (NC), MCI, and individuals with Alzheimer's
      disease. Amyloid imaging and magnetic resonance imaging (MRI) summaries were
      assessed as predictors of disease progression. RESULTS: Relative progression of
      markers supports parts of the amyloid cascade hypothesis, although evidence of
      earlier occurrence of cognitive change exists. SMC are similar to NC, whereas
      eMCI fall between the cognitively normal and MCI groups. Amyloid leads to faster
      conversion and increased cognitive impairment. DISCUSSION: Analyses support
      features of the amyloid hypothesis, but also illustrate the considerable
      heterogeneity in the aging process.

PMID- 26194316
TI  - The Alzheimer's Disease Neuroimaging Initiative informatics core: A decade in
      review.
AB  - The Informatics Core of the Alzheimer's Disease Neuroimaging Initiative has
      coordinated data integration and dissemination for a continually growing and
      complex data set in which both data contributors and recipients span
      institutions, scientific disciplines, and geographic boundaries. This article
      provides an update on the accomplishments and future plans. 

PMID- 26194313
TI  - Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress,
      opportunities, and plans.
AB  - INTRODUCTION: Genetic data from the Alzheimer's Disease Neuroimaging Initiative
      (ADNI) have been crucial in advancing the understanding of Alzheimer's disease
      (AD) pathophysiology. Here, we provide an update on sample collection, scientific
      progress and opportunities, conceptual issues, and future plans. METHODS:
      Lymphoblastoid cell lines and DNA and RNA samples from blood have been collected
      and banked, and data and biosamples have been widely disseminated. To date, APOE
      genotyping, genome-wide association study (GWAS), and whole exome and whole
      genome sequencing data have been obtained and disseminated. RESULTS: ADNI genetic
      data have been downloaded thousands of times, and >300 publications have
      resulted, including reports of large-scale GWAS by consortia to which ADNI
      contributed. Many of the first applications of quantitative endophenotype
      association studies used ADNI data, including some of the earliest GWAS and
      pathway-based studies of biospecimen and imaging biomarkers, as well as memory
      and other clinical/cognitive variables. Other contributions include some of the
      first whole exome and whole genome sequencing data sets and reports in healthy
      controls, mild cognitive impairment, and AD. DISCUSSION: Numerous genetic
      susceptibility and protective markers for AD and disease biomarkers have been
      identified and replicated using ADNI data and have heavily implicated immune,
      mitochondrial, cell cycle/fate, and other biological processes. Early sequencing
      studies suggest that rare and structural variants are likely to account for
      significant additional phenotypic variation. Longitudinal analyses of
      transcriptomic, proteomic, metabolomic, and epigenomic changes will also further
      elucidate dynamic processes underlying preclinical and prodromal stages of
      disease. Integration of this unique collection of multiomics data within a
      systems biology framework will help to separate truly informative markers of
      early disease mechanisms and potential novel therapeutic targets from the vast
      background of less relevant biological processes. Fortunately, a broad swath of
      the scientific community has accepted this grand challenge.

PMID- 26194317
TI  - Perspective: The Alzheimer's Disease Neuroimaging Initiative and the role and
      contributions of the Private Partner Scientific Board (PPSB).
AB  - The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partner Scientific
      Board (PPSB) is comprised of representatives of private, for-profit entities
      (including pharmaceutical, biotechnology, diagnostics, imaging companies, and
      imaging contract research organizations), and nonprofit organizations that
      provide financial and scientific support to ADNI through the Foundation for the
      National Institutes of Health. The PPSB serves as an independent, open, and
      precompetitive forum in which all private sector and not-for-profit partners in
      ADNI can collaborate, share information, and offer scientific and private-sector
      perspectives and expertise on issues relating to the ADNI project. In this
      article, we review and highlight the role, activities, and contributions of the
      PPSB within the ADNI project, and provide a perspective on remaining unmet needs
      and future directions. 

PMID- 26194318
TI  - The Worldwide Alzheimer's Disease Neuroimaging Initiative: An update.
AB  - The Alzheimer's Disease Neuroimaging Initiative (ADNI), launched in 2004, has
      worked to accelerate drug development by validating imaging and
      blood/cerebrospinal fluid biomarkers for Alzheimer's disease clinical treatment
      trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A
      true public-private partnership, the initiative has set a new standard for data
      sharing without embargo and for the use of biomarkers in dementia research. The
      ADNI effort in North America is not the only such effort in the world. The
      Alzheimer's Association recognized these global efforts and formed Worldwide ADNI
      (WW-ADNI). By creating a platform for international collaboration and
      cooperation, WW-ADNI's goals are to harmonize projects and results across
      geographical regions and to facilitate data management and availability to
      investigators around the world. WW-ADNI projects include those based in North
      America, Europe, Japan, Australia, Korea, and Argentina. 

PMID- 26194319
TI  - The impact of the Alzheimer's Disease Neuroimaging Initiative 2: What role do
      public-private partnerships have in pushing the boundaries of clinical and basic
      science research on Alzheimer's disease?
AB  - In the growing landscape of biomedical public-private-partnerships, particularly
      for Alzheimer's disease, the question is posed as to their value. What impacts do
      public-private-partnerships have on clinical and basic science research in
      Alzheimer's disease? The authors answer the question using the Alzheimer's
      Disease Neuroimaging Initiative (ADNI) as a test case and example. ADNI is an
      exemplar of how public-private-partnerships can make an impact not only on
      clinical and basic science research and practice (including clinical trials), but
      also of how similar partnerships using ADNI as an example, can be designed to
      create a maximal impact within their fields. 

PMID- 26194321
TI  - Donepezil attenuates high glucose-accelerated senescence in human umbilical vein
      endothelial cells through SIRT1 activation.
AB  - Cellular senescence of endothelial cells is a damage and stress response which
      induces pro-inflammatory, pro-atherosclerotic, and pro-thrombotic phenotypes.
      Donepezil is a drug used for the treatment of mild to moderate dementia of the
      Alzheimer's disease (AD). The aim of the present study was to investigate the
      attenuation of endothelial cell senescence by donepezil and to explore the
      mechanisms underlying the anti-aging effects of donepezil. Our results indicated
      that high glucose (HG) markedly decreased cell viability of human umbilical vein
      endothelial cells (HUVECs), and this phenomenon was reversed by treatment with
      donepezil. Importantly, our results displayed that the frequency of senescent (SA
      beta-gal-positive) cells and the expression level of senescence genes (PAI-1 and
      p21) were significantly higher in the HG group compared with the normal glucose
      (NG) group, and these changes were blocked by treatment with donepezil. Also, our
      results showed that donepezil inhibits the generation of reactive oxygen species
      (ROS), which promotes cellular senescence. Pretreatment with nicotinamide (NAM),
      a sirtuin 1 (SIRT1) inhibitor, inhibited the reduction in senescence associated
      with donepezil. Indeed, our results indicated that donepezil increased the SIRT1
      enzyme activity. Therefore, these results show that donepezil delays cellular
      senescence that is promoted under HG condition via activation of SIRT1. 

PMID- 26194322
TI  - Hsp27 and Hsp70 in chronic obstructive pulmonary disease: certainties vs doubts.

PMID- 26194323
TI  - Do cardiac actin mutations lead to altered actomyosin interactions?
AB  - It is currently hypothesized that increased heart muscle contractility leads to
      hypertrophic cardiomyopathy (HCM), and reduced contractility leads to dilated
      cardiomyopathy (DCM). To determine if changes in the core interaction between
      actin and myosin occur due to mutations in the cardiac actin gene (ACTC), we
      measured the interactions between myosin and 8 ACTC mutant proteins found in
      patients with HCM or DCM. R312H showed a decreased actin-activated myosin S1
      ATPase rate (13.1 +/- 0.63 MUmol/L/min) compared to WT (15.3 +/- 1.6
      MUmol/L/min), whereas the rate with E99K was significantly higher (20.1 +/- 1.5
      MUmol/L/min). In vitro motility assays with varying ATP concentrations showed
      that the KM for E99K remains unchanged with a significantly decreased Vmax (1.90
      +/- 0.37 MUm/sec) compared to WT (3.33 +/- 0.46 MUm/sec). Based on a 5 nm myosin
      step size, we calculated a duty ratio of approximately 0.04 for WT and the
      majority of mutant actins; however, the duty ratio for E99K was twice as high.
      Based on our analysis of 8 ACTC mutants, we infer that mutations in ACTC lead to
      disease through various molecular mechanisms. While changes in actomyosin
      interactions with the E99K mutation might cause increased ATP usage and tension
      leading to HCM, measurable changes in the basic interaction between actin and
      myosin do not appear to be involved in the mechanisms of disease development for
      the other ACTC mutants tested. 

PMID- 26194320
TI  - Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014.
AB  - INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) was
      established in 2004 to facilitate the development of effective treatments for
      Alzheimer's disease (AD) by validating biomarkers for AD clinical trials.
      METHODS: We searched for ADNI publications using established methods. RESULTS:
      ADNI has (1) developed standardized biomarkers for use in clinical trial subject
      selection and as surrogate outcome measures; (2) standardized protocols for use
      across multiple centers; (3) initiated worldwide ADNI; (4) inspired initiatives
      investigating traumatic brain injury and post-traumatic stress disorder in
      military populations, and depression, respectively, as an AD risk factor; (5)
      acted as a data-sharing model; (6) generated data used in over 600 publications,
      leading to the identification of novel AD risk alleles, and an understanding of
      the relationship between biomarkers and AD progression; and (7) inspired other
      public-private partnerships developing biomarkers for Parkinson's disease and
      multiple sclerosis. DISCUSSION: ADNI has made myriad impacts in its first decade.
      A competitive renewal of the project in 2015 would see the use of newly developed
      tau imaging ligands, and the continued development of recruitment strategies and
      outcome measures for clinical trials.

PMID- 26194324
TI  - When Opportunity Knocks Twice: Dual Living Kidney Donation, Autonomy and the
      Public Interest.
AB  - Living kidney transplantation offers the best treatment in terms of life
      expectancy and quality of life for those with end-stage renal disease. The long
      term risks of living donor nephrectomy, although real, are very small, with
      evidence of good medium-term outcomes. Who should be entitled to donate, and in
      which circumstances, is nevertheless a live question. We explore the ethical
      dimensions of a request by an individual to donate both of their kidneys during
      life: 'dual living kidney donation'. Our ethical analysis is tethered to a
      hypothetical case study in which a father asks to donate a kidney to each of his
      twin boys. We explore the autonomy of the protagonists, alongside different
      dimensions of the public interest, such as the need to protect not only the
      recipients, but also the donor and even the wider community. Whilst acknowledging
      objections to 'dual-donation', not least by reference to the harms that the donor
      might be expected to endure, we suggest there is a prima facie case for
      permitting this, provided that both donor and recipients are willing and that due
      attention is paid to such considerations as the autonomy and welfare of all
      parties, as well as to the wider ramifications of acting on such a request. We
      argue for broader interpretations of the concepts of autonomy and welfare,
      recognizing the importance of relationships and the relevance of more than merely
      physical well-being. Equipped with such a holistic assessment, we suggest there
      is a prima facie case for allowing 'dual living kidney donation'. 

PMID- 26194325
TI  - Mothers' perceptions of their health choices, related duties and
      responsibilities: A qualitative interview study.
AB  - OBJECTIVE: to describe mothers' perceptions of their health choices, related
      duties and responsibilities. DESIGN: descriptive exploratory study with
      qualitative research method. SETTING: interviews conducted after the clients'
      regular health visits to one publicly provided maternity clinic in a southern
      city in Finland. PARTICIPANTS: 13 mothers aged between 21 and 40-years-old, who
      were pregnant or had given birth in the past four weeks. Six of participants were
      pregnant or had delivered for first time and it was the second to fourth
      pregnancy for the remainder. DATA COLLECTION AND DATA ANALYSIS: one-to-one semi
      structured interviews using the inductive content analysis method. FINDINGS:
      women reported increased responsibility for their health choices for themselves
      and their baby during pregnancy. However, their duties and responsibilities were
      seldom discussed at maternity clinics. The duty to reconsider their health
      choices was described as a predictor of commitment to their pregnancy and
      motherhood, but they recognised that it required sufficient knowledge to realise
      this. In addition, the mothers said their health choices changed from private to
      one of public interest during this period. CONCLUSIONS: health choices are
      connected to maternal duties and responsibilities, but they can sometimes lack
      clarity during this new phase of life. In future, more research should be
      conducted to study maternal duties and responsibilities in different contexts.
      IMPLICATIONS FOR PRACTICE: findings highlight the skills of nurses and midwives
      at maternity clinics to discuss and support mothers' moral pondering during
      pregnancy. Although health choices in general are well recognised as a part of
      maternal counselling, these findings suggest a moral perspective should be
      incorporated into the advice that is provided.

PMID- 26194326
TI  - A preterm lifeline: Early discharge programme based on family-centred care.
AB  - PURPOSE: To present an Early Discharge Programme model for preterm infants based
      on family-centred care, and to describe its impact on the infants and families.
      DESIGN AND METHODS: Methods included longitudinal growth assessments of 218
      premature infants and a qualitative synthesis of two focus group interviews with
      15 parents. RESULTS: The main finding was the experience of "parents in control
      with lifeline to neonatal intensive care unit" based on five syntheses. PRACTICE
      IMPLICATIONS: An early discharge programme based on family-centred care has been
      implemented and integrated into our neonatal intensive care unit that could be
      implemented by other hospitals.

PMID- 26194327
TI  - Mutations in the three Arabidopsis genes that encode the E2 subunit of the
      mitochondrial pyruvate dehydrogenase complex differentially affect enzymatic
      activity and plant growth.
AB  - KEY MESSAGE: Three members of the E2 subunit of the Arabidopsis mitochondrial
      pyruvate dehydrogenase (mtPDC) complex differentially affect mtPDC activity and
      plant growth. In all organisms, the mitochondrial pyruvate dehydrogenase complex
      (mtPDC) consists of three components: E1, E2, and E3. In this multi-enzyme
      complex, the E2 subunits form the core structure. In Arabidopsis, the E2 subunits
      are encoded by three genes: mtE2-1, mtE2-2, and mtE2-3. The contribution of each
      mtE2 gene to total mtPDC activity, however, is unknown. In this study, we show
      that knockdown of the expression of the mtE2-1 gene to 17% of that in the wild
      type has only a slight effect on plant growth whereas knockout of mtE2-2 leads to
      an embryo-lethal phenotype. The nearly null mutation of mtE2-3 does not cause any
      developmental abnormality. Based on these results, we conclude that mtE2-2 plays
      a major role in determining the total activity of the mtPDC in Arabidopsis while
      mtE2-1 and mtE2-3 are more or less functionally redundant with mtE2-2 under
      normal growth condition. Our results provide genetic evidence for a recently
      proposed novel mechanism that regulates plant mtPDC activity.

PMID- 26194328
TI  - Xanthones from roots, hairy roots and cell suspension cultures of selected
      Hypericum species and their antifungal activity against Candida albicans.
AB  - KEY MESSAGE: Highest xanthone contents were found in Hypericum pulchrum and H.
      annulatum untransformed roots. The best anti- Candida activity was obtained for
      hairy roots extracts of H. tetrapterum clone 2 ATCC 15834. Extracts of root
      cultures, hairy roots and cell suspensions of selected Hypericum spp. were
      screened for the presence of xanthones and tested for their antifungal activity
      against Candida albicans strain ATCC 10231. At least one of the following
      xanthones, 5-methoxy-2-deprenylrheediaxanthone; 1,3,6,7-tetrahydroxyxanthone;
      1,3,5,6-tetrahydroxyxanthone; paxanthone; kielcorin or mangiferin was identified
      in methanolic extracts of the untransformed root cultures. The highest total
      xanthone content, with five xanthones, was found in untransformed H. pulchrum and
      H. annulatum root cultures. Hairy roots and the controls of H. tetrapterum
      contained 1,7-dihydroxyxanthone, while hairy root cultures and the corresponding
      controls of H. tomentosum contained toxyloxanthone B, 1,3,6,7- and 1,3,5,6
      tetrahydroxyxanthone. Two xanthones, cadensin G and paxanthone, were identified
      in cell suspension cultures of H. perforatum. Their content increased about two
      fold following elicitation with salicylic acid. The anti-Candida activity of the
      obtained extracts ranged from MIC 64 to >256 ug ml(-1). Among the extracts of
      Hypericum untransformed roots, the best antifungal activity was obtained for
      extracts of H. annulatum grown under CD conditions. Extracts of hairy roots
      clones A4 and 7 ATCC15834 of H. tomentosum and clone 2 ATCC15834 of H.
      tetrapterum displayed inhibition of 90% of Candida growth with 256 MUg ml(-1).
      Extracts from chitosan-elicitated cells did not show antifungal activity.

PMID- 26194329
TI  - Ceratomyxa tunisiensis n. sp. (Myxosporea: Bivalvulida) from the Gallbladders of
      Two Carangid Fish Caught Off the Coast of Tunisia.
AB  - A new coelozoic Myxozoan species, Ceratomyxa tunisiensis n. sp., was found
      infecting the gallbladders of two carangid fish, Caranx rhonchus and Trachurus
      trachurus (Perciforme, Carangidae), from the Gulf of Gabes, on the southern coast
      of Tunisia. The parasite develops in spherical mono-, diplo-, or polysporic
      tropozoites in the gallbladder of the hosts. Mature spores are typical of the
      genus Ceratomyxa. They are transversely elongated and narrowly crescent-shaped
      with a slightly convex anterior and concave posterior, and measure 23 +/- 0. 27
      (20-25) MUm width * 6 +/- 0.26 (5-8) MUm in length. Spore shell valves are
      symmetrical with rounded ends. Two spherical polar capsules situated on either
      side of the sutural line measure 2.2 MUm (2.0-3.0) in diam. Periodical sampling
      of C. rhonchus and T. trachurus from Marsh 2012 to February 2013 showed that
      infection due to C. tunisiensis occurs in 59% and 69% of the examined fish,
      respectively. Molecular analysis based on the small subunit (SSU) rRNA sequence
      shows high genetic divergence with all other ceratomyxid species. A Maximum
      Likelihood phylogenetic tree shows association with the species C. leatharjecketi
      Fiala, kova, Kodadkova, Freeman, Bartosova-Sojkova, and Atkinson, 2015 reported
      from the gallbladder of Aluterusmonoceros (L.) caught in the Andaman Sea, off
      Malaysia. Nonetheless, the SSU rRNA sequences of C. tunisiensis and C.
      leatharjecketi have only a 90% similarity.

PMID- 26194330
TI  - Impact of using different guideline recommended serum natriuretic peptide
      thresholds on the diagnosis and referral rates of a diagnostic heart failure
      clinic.
AB  - AIMS: The aims of this study were to determine the diagnostic yield of a
      dedicated heart failure diagnosis clinic and the impact of using different
      guideline recommended N-terminal pro B-type natriuretic peptide (NT-proBNP)
      referral thresholds on diagnosis and referral patterns. METHODS AND RESULTS:
      Patients referred by primary care between September 2011 and May 2013 were
      included in the analysis. Data collected included baseline characteristics, NT
      proBNP levels, echocardiographic and clinical findings, final diagnosis and
      outcome. The impact of using Newcastle (locally modified age-adjusted NT-proBNP
      thresholds), National Institute for Health and Care Excellence (NICE) and
      European Society of Cardiology (ESC) NT-proBNP thresholds on diagnosis and
      referrals was determined by applying the different guidelines to this population.
      A total of 208 patients were referred; median age 77.5 years and 62.5% were
      women. Thirty-four patients (16.3%) had systolic heart failure, 50 patients
      (24.0%) had heart failure with preserved ejection fraction. One hundred and six
      patients (51.0%) did not have heart failure. Using NICE guidelines (NT-proBNP >=
      400 ng/l) instead of the Newcastle age-adjusted NT-proBNP referral thresholds
      results in 59 fewer referrals, but eight heart failure diagnoses were missed.
      Using the ESC cut-off of NT-proBNP >= 125 ng/l would result in 88 additional
      referrals; one diagnosis of heart failure would be missed. Over a mean follow-up
      of 16.8 +/- 6 months there were 21 deaths and 47 hospital admissions. CONCLUSION:
      The Newcastle age-adjusted thresholds led to more referrals in comparison to NICE
      guidelines but are more sensitive in diagnosing heart failure. Using ESC
      recommended thresholds results in a similar diagnostic yield to our age-adjusted
      thresholds, but has the potential to significantly increase the referrals in
      patients >= 75 years, which may result in a lower diagnostic yield.

PMID- 26194331
TI  - Protective effect of Blumea lacera DC aerial parts in indomethacin-induced
      enterocolitis in rats.
AB  - Traditionally Blumea lacera DC is used to treat inflammation and bowel ailments.
      Lack of specific, curative treatment for IBD enticed us to investigate the
      therapeutic efficacy of ethanolic extract of aerial parts of Blumea lacera DC
      (EEBL) against indomethacin-induced enterocolitis. Male Wistar rats were divided
      into six groups (n = 5) and different doses of EEBL (100 and 200 mg/kg, p.o) and
      sulphasalazine (100 mg/kg, p.o) were administered for seven days. Enterocolitis
      was induced by two subsequent doses of indomethacin (7.5 mg/kg, s.c) on 7th and
      8th day. Treatments were continued up to 12th day and sacrificed. The protective
      effect was assessed on the basis of macroscopic scores of ileum strips, changes
      in biochemical parameters such as serum lactate dehydrogenase (LDH), tissue
      myeloperoxidase (MPO), lipid peroxidation (LPO), and total thiols (TT). Further,
      activity was ascertained by histopathological evaluations. HPLC fingerprinting
      profiling of EEBL was also carried out. Pre-treatment with EEBL or sulphasalazine
      significantly attenuated the indomethacin-induced proximal ileal damage, elevated
      levels of serum LDH, tissue MPO, LPO and lower levels of TT. Further, observed
      activity of EEBL was well correlated with histopathological alterations. The
      results revealed the protective action of the title plant against the
      indomethacin-induced enterocolitis in rats, which might be attributed by its
      antioxidant, anti-inflammatory, antimicrobial, and membrane-stabilizing
      properties.

PMID- 26194332
TI  - Influence of chronic kidney disease on cardiac structure and function.
AB  - Chronic kidney disease (CKD), the presence of kidney dysfunction and/or damage,
      is a worldwide public health issue. Although CKD is independently associated with
      various subtypes of cardiovascular diseases, a recent international collaborative
      meta-analysis demonstrates that CKD is particularly strongly associated with
      heart failure, suggesting its critical impact on cardiac structure and function.
      Although numerous studies have investigated the association of CKD and cardiac
      structure and function, these studies substantially vary regarding source
      populations and methodology (e.g., measures of CKD and/or parameters of cardiac
      structure and function), making it difficult to reach universal conclusions.
      Nevertheless, in this review, we comprehensively examine relevant studies,
      discuss potential mechanisms linking CKD to alteration of cardiac structure and
      function, and demonstrate clinical implications as well as potential future
      research directions. We exclusively focus on studies investigating both CKD
      measures, kidney function (i.e., glomerular filtration rate [GFR], creatinine
      clearance, or levels of filtration markers), and kidney damage represented by
      albuminuria, since current international clinical guidelines of CKD recommend
      staging CKD and assessing its clinical risk based on both GFR and albuminuria. 

PMID- 26194333
TI  - Sugar-Sweetened Beverages and Obesity Risk in Children and Adolescents: A
      Systematic Analysis on How Methodological Quality May Influence Conclusions.
AB  - BACKGROUND: In the context of a worldwide high prevalence of childhood obesity,
      the role of sugar-sweetened beverage (SSB) consumption as a cause of excess
      weight gain remains controversial. Conflicting results may be due to
      methodological issues in original studies and in reviews. OBJECTIVE: The aim of
      this review was to systematically analyze the methodology of studies
      investigating the influence of SSB consumption on risk of obesity and obesity
      among children and adolescents, and the studies' ability to answer this research
      question. METHODS: A systematic review of cohort and experimental studies
      published until December 2013 in peer-reviewed journals was performed on Medline,
      CINAHL, Web of Knowledge, and ClinicalTrials.gov. Studies investigating the
      influence of SSB consumption on risk of obesity and obesity among children and
      adolescents were included, and methodological quality to answer this question was
      assessed independently by two investigators using the Academy of Nutrition and
      Dietetics Quality Criteria Checklist. RESULTS: Among the 32 identified studies,
      nine had positive quality ratings and 23 studies had at least one major
      methodological issue. Main methodological issues included SSB definition and
      inadequate measurement of exposure. Studies with positive quality ratings found
      an association between SSB consumption and risk of obesity or obesity (n=5) (ie,
      when SSB consumption increased so did obesity) or mixed results (n=4). Studies
      with a neutral quality rating found a positive association (n=7), mixed results
      (n=9), or no association (n=7). CONCLUSIONS: The present review shows that the
      majority of studies with strong methodology indicated a positive association
      between SSB consumption and risk of obesity or obesity, especially among
      overweight children. In addition, study findings highlight the need for the
      careful and precise measurement of the consumption of SSBs and of important
      confounders.

PMID- 26194334
TI  - Interference of melanin in the susceptibility profile of Sporothrix species to
      amphotericin B.
AB  - BACKGROUND: The presence of melanin in the fungal cell is a major virulence
      factor of the genus Sporothrix since it protects the fungal cells against the
      defense systems. AIMS: The present study aimed to investigate the interference of
      melanin in the susceptibility of Sporothrix brasiliensis and Sporothrix schenckii
      sensu stricto to amphotericin B and itraconazole, drugs recommended as therapy
      for disseminated and subcutaneous sporotrichosis, respectively. METHODS: Yeast
      cells were cultivated in minimal medium with or without l-DOPA in order to induce
      the production of melanin. Microdilution and killing assay methods were used to
      determine the antifungal activity against yeast cells with different amounts of
      melanin. RESULTS: The killing assay showed that melanization protected isolates
      within the S. schenckii complex from amphotericin B, particularly in the lower
      concentrations tested. CONCLUSIONS: Studies combining amphotericin B and
      inhibitors of melanin are required in order to avoid this effect.

PMID- 26194335
TI  - Tunable dipole induced hydrogen bonds between a hydrogen molecule and alkali
      halides.
AB  - Hydrogen bonding (HB) systems are known to be X-H???Y type complexes, which are
      called conventional HB systems if the X and Y are strongly electronegative atoms
      such as O, N and halides or unconventional systems if the X is replaced by C. In
      this study, we devise a new dipole-induced HB that is formed between a hydrogen
      molecule and an alkali halide using ab initio calculations. The HB is depicted as
      H-H???Y-M, in which MY are alkali halides. Analysis of the possible structures
      and properties of the proposed compounds, including their geometries,
      frequencies, bond strength, and natural charge distribution, as well as a
      topological analysis of electronic density, shows that the large dipole moment of
      the Y-M molecule is responsible for the generation of the proposed HB. We also
      find that the strength of HB can be tuned by adopting MY with various polarities.
      We hope that our findings could provide a new insight into HB.

PMID- 26194336
TI  - Monoclonal B-cell lymphocytosis and hypogammaglobulinaemia.

PMID- 26194337
TI  - 24 h Accelerometry: impact of sleep-screening methods on estimates of sedentary
      behaviour and physical activity while awake.
AB  - Although accelerometers can assess sleep and activity over 24 h, sleep data must
      be removed before physical activity and sedentary time can be examined
      appropriately. We compared the effect of 6 different sleep-scoring rules on
      physical activity and sedentary time. Activity and sleep were obtained by
      accelerometry (ActiGraph GT3X) over 7 days in 291 children (51.3% overweight or
      obese) aged 4-8.9 years. Three methods removed sleep using individualised time
      filters and two methods applied standard time filters to remove sleep each day (9
      pm-6 am, 12 am-6 am). The final method did not remove sleep but simply defined
      non-wear as at least 60 min of consecutive zeros over the 24-h period. Different
      methods of removing sleep from 24-h data markedly affect estimates of sedentary
      time, yielding values ranging from 556 to 1145 min/day. Estimates of non-wear
      time (33-193 min), wear time (736-1337 min) and counts per minute (384-658) also
      showed considerable variation. By contrast, estimates of moderate-to-vigorous
      activity (MVPA) were similar, varying by less than 1 min/day. Different scoring
      methods to remove sleep from 24-h accelerometry data do not affect measures of
      MVPA, whereas estimates of counts per minute and sedentary time depend
      considerably on which technique is used. 

PMID- 26194338
TI  - Adolescent Body Image Distortion: A Consideration of Immigrant Generational
      Status, Immigrant Concentration, Sex and Body Dissatisfaction.
AB  - Immigrant adolescents represent a significant and growing proportion of the
      population in the United States. Yet, little is known about their experiences of
      body image distortion. This is particularly concerning given that body image
      distortion has been identified as a significant and modifiable risk factor for a
      number of mental illnesses, including depression and eating disorders. This study
      uses multi-level modeling to examine the associations between immigrant
      generational status, neighborhood immigrant concentration, sex, body
      dissatisfaction and risk for body image distortion. Data come from the National
      Longitudinal Study of Adolescent Health and includes 10,962 11-19 year olds (49.6
      % female). First generation immigrant females were significantly more likely than
      3rd generation-or-later adolescents to experience underweight body image
      distortion. There was no association between neighborhood immigrant concentration
      and risk for body image distortion. Body dissatisfaction was associated with
      greater risk for underweight and overweight body image distortion, with the
      magnitude of underweight distortion risk significantly greater among 1st
      generation immigrants. Interventions that encourage the development of a healthy
      body image have the potential to reduce the onset and duration of body image
      distortion among immigrant and non-immigrant adolescents.

PMID- 26194340
TI  - Cytopathology meets basic science.

PMID- 26194339
TI  - Dopamine D1/D5 receptor signaling regulates synaptic cooperation and competition
      in hippocampal CA1 pyramidal neurons via sustained ERK1/2 activation.
AB  - Synaptic cooperation and competition are important components of synaptic
      plasticity that tune synapses for the formation of associative long-term
      plasticity, a cellular correlate of associative long-term memory. We have
      recently reported that coincidental activation of weak synapses within the
      vicinity of potentiated synapses will alter the cooperative state of synapses to
      a competitive state thus leading to the slow decay of long-term plasticity, but
      the molecular mechanism underlying this is still unknown. Here, using acute
      hippocampal slices of rats, we have examined how increasing extracellular
      dopamine concentrations interact and/or affect electrically induced long-term
      potentiation (LTP) in the neighboring synapses. We demonstrate that D1/D5
      receptor-mediated potentiation at the CA1 Schaffer collateral synapses
      differentially regulates synaptic co-operation and competition. Further
      investigating the molecular players involved, we reveal an important role for
      extracellular signal-regulated kinases-1 and 2 (ERK1/2) as signal integrators and
      dose-sensors. Interestingly, a sustained activation of ERK1/2 pathway seems to be
      involved in the differential regulation of synaptic associativity. The
      concentration-dependent effects of the modulatory transmitter, as demonstrated
      for dopaminergic signaling in the present study, might offer additional
      computational power by fine tuning synaptic associativity processes for
      establishing long-term associative memory in neural networks.

PMID- 26194341
TI  - Recognition and identification of active components from Radix Bupleuri using
      human neuroblastoma SH-SY5Y cells.
AB  - The aim of the study was to screen active components of Radix Bupleuri (a
      traditional Chinese herb) and discover novel anti-schizophrenic candidate drugs
      using human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were used for preparation
      of the stationary phase in the cell membrane chromatography model. Retention
      components by the SH-SY5Y/CMC model were collected and then analyzed by GC/MS
      under the optimized conditions in offline conditions. After investigating the
      suitability and reliability of the SH-SY5Y/CMC method using amisulpride and
      haloperidol as standard compounds, this method was applied to screening active
      components from the extracts of Radix Bupleuri. Retention components of SH
      SY5Y/CMC model were saikosaponin A, saikosaponin B1, saikosaponin B2,
      saikosaponin C and saikosaponin D, which were identified by the GC/MS method. In
      vitro pharmacological trials-MTT, saikosaponin B1, saikosaponin B2 and
      saikosaponin C could protect SY5Y cells. The protective effects of saikosaponin
      B1 and saikosaponin C were concentration dependent. Saikosaponin A and
      saikosaponin D inhibited cell viability at concentrations >30 ug/mL (p < 0.05).
      Via SH-SY5Y/CMC method and SH-SY5Y MTT trial, we rapidly detected target
      components from Radix Bupleuri, accurately identified them and determined their
      different effects on SH-SY5Y cells. Saikosaponin B1, saikosaponin B2 and
      saikosaponin C may be anti-schizophrenic candidate drugs.

PMID- 26194342
TI  - Lethal trap trees: a potential option for emerald ash borer (Agrilus planipennis
      Fairmaire) management.
AB  - BACKGROUND: Economic and ecological impacts of ash (Fraxinus spp.) mortality
      resulting from emerald ash borer (EAB) (Agrilus planipennis Fairmaire) invasion
      are severe in forested, residential and urban areas. Management options include
      girdling ash trees to attract ovipositing adult beetles and then destroying
      infested trees before larvae develop or protecting ash with a highly effective,
      systemic emamectin benzoate insecticide. Injecting this insecticide and then
      girdling injected trees a few weeks later could effectively create lethal trap
      trees, similar to a bait-and-kill tactic, if girdling does not interfere with
      insecticide translocation. We compared EAB larval densities on girdled trees,
      trees injected with the emamectin benzoate insecticide, trees injected with the
      insecticide and then girdled 18-21 days later and untreated controls at multiple
      sites. RESULTS: Pretreatment larval densities did not differ among treatments.
      Current-year larval densities were higher on girdled and control trees than on
      any trees treated with insecticide at all sites. Foliar residue analysis and
      adult EAB bioassays showed that girdling trees after insecticide injections did
      not reduce insecticide translocation. CONCLUSIONS: Girdling ash trees to attract
      adult EAB did not reduce efficacy of emamectin benzoate trunk injections applied
      >= 18 days earlier and could potentially be used in integrated management
      programs to slow EAB population growth.

PMID- 26194344
TI  - LoMA-B: a simple and versatile lab-on-a-chip system based on single-channel
      bisulfite conversion for DNA methylation analysis.
AB  - Miniaturized lab-on-a-chip (LOC) systems have been developed for genetic and
      epigenetic analyses in clinical applications because of advantages such as
      reduced sample size and reagent consumption, rapid processing speed, simplicity,
      and enhanced sensitivity. Despite tremendous efforts made towards developing LOC
      systems for use in the clinical setting, the development of LOC systems to
      analyze DNA methylation, which is an emerging epigenetic marker causing the
      abnormal silencing of genes including tumor suppressor genes, is still
      challenging because of the gold standard methods involving a bisulfite conversion
      step. Existing bisulfite conversion-based techniques are not suitable for
      clinical use due to their long processing time, labor intensiveness, and the
      purification steps involved. Here, we present a lab-on-a-chip system for DNA
      methylation analysis based on bisulfite conversion (LoMA-B), which couples a
      sample pre-processing module for on-chip bisulfite conversion and a label-free,
      real-time detection module for rapid analysis of DNA methylation status using an
      isothermal DNA amplification/detection technique. The methylation status of the
      RARbeta gene in human genomic DNA extracted from MCF-7 cells was analyzed by the
      LoMA-B system within 80 min (except 16 h for sensor preparation) compared to
      conventional MS-PCR within 24 h. Furthermore, the LoMA-B system is highly
      sensitive and can detect as little as 1% methylated DNA in a
      methylated/unmethylated cell mixture. Therefore, the LoMA-B system is an
      efficient diagnostic tool for the simple, versatile, and quantitative evaluation
      of DNA methylation patterns for clinical applications. 

PMID- 26194343
TI  - Prognostic significance of copy number alterations in adolescent and adult
      patients with precursor B acute lymphoblastic leukemia enrolled in PETHEMA
      protocols.
AB  - BACKGROUND: Some copy number alterations (CNAs) have independent prognostic
      significance for adults with acute lymphoblastic leukemia (ALL). METHODS: This
      study analyzed via multiplex ligation-dependent probe amplification the frequency
      and prognostic impact of CNAs of 12 genetic regions in 142 adolescents and adults
      with de novo precursor B-cell ALL. RESULTS: The cyclin-dependent kinase inhibitor
      2A/B (CDKN2A/B) deletion (59 of 142 or 42%) was the most frequent CNA, and it was
      followed by Ikaros family zinc finger 1 (IKZF1) losses (49 of 142 or 35%). IKZF1
      deletions were more prevalent in Philadelphia chromosome (Ph)-positive ALL and
      were associated with advanced age and high white blood cell (WBC) counts. The
      multivariate analysis showed that advanced age and early B-cell factor 1 (EBF1)
      deletions were associated with chemotherapy resistance in both the whole series
      (hazard ratios, 0.949 and 0.135, respectively) and the Ph-negative subgroup
      (hazard ratios, 0.946 and 0.118, respectively). High WBC counts and focal IKZF1
      deletions correlated with disease recurrence (hazard ratios, 1.005 and 1.869,
      respectively), whereas advanced age and CDKN2A/B losses influenced overall
      survival in both the whole series (hazard ratios, 1.038 and 2.545, respectively)
      and the Ph-negative subgroup (hazard ratios, 1.044 and 2.105, respectively).
      CONCLUSIONS: Deletions of EBF1, IKZF1, and CDKN2A/B have an independent adverse
      prognosis for adolescents and adults with B-precursor ALL, and this suggests that
      these CNAs should be included in the initial risk assessment of ALL.

PMID- 26194345
TI  - Ocotillol, a Majonoside R2 Metabolite, Ameliorates 2,4,6-Trinitrobenzenesulfonic
      Acid-Induced Colitis in Mice by Restoring the Balance of Th17/Treg Cells.
AB  - In a preliminary experiment, majonoside R2 (MR2), isolated from Vietnamese
      ginseng (Panax vietnamensis Ha et Grushv.), inhibited differentiation to Th17
      cells and was metabolized to ocotillol via pseudoginsenoside RT4 (PRT4) by gut
      microbiota. Therefore, we examined the inhibitory effects of MR2 and its
      metabolites PRT4 and ocotillol against Th17 cell differentiation. These
      ginsenosides significantly suppressed interleukin (IL)-6/tumor growth factor beta
      induced differentiation of splenic CD4(+) T cells into Th17 cells and expression
      of IL-17 in vitro. Among these ginsenosides, ocotillol showed the highest
      inhibitory effect. We also examined the anti-inflammatory effect of ocotillol in
      mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Oral
      administration of ocotillol significantly suppressed TNBS-induced colon
      shortening, macroscopic score, myeloperoxidase activity, and production of nitric
      oxide and prostaglandin E2. Ocotillol treatment increased TNBS-suppressed
      expression of tight junction proteins ZO-1, occludin, and claudin-1 in the colon.
      Treatment with ocotillol inhibited TNBS-induced expression of tumor necrosis
      factor (TNF)-alpha and IL-1beta, as well as activation of NF-kappaB and MAPKs.
      Moreover, treatment with ocotillol inhibited TNBS- induced differentiation to
      Th17 cells in the lamina propria of colon, as well as expression of T-bet,
      RORgammat, IL-17, and IL-23. Ocotillol treatment also increased Treg cell
      differentiation and Foxp3 and IL-10 expression. These findings suggest that
      orally administered MR2 may be metabolized to ocotillol in the intestine by gut
      microbiota and the transformed ocotillol may ameliorate inflammatory diseases
      such as colitis by restoring the balance of Th17/Treg cells. 

PMID- 26194348
TI  - Ending overly broad HIV criminalization: Canadian scientists and clinicians stand
      for justice.
AB  - In Canada, people living with HIV who do not disclose their HIV status prior to
      sexual acts risk prosecution for aggravated sexual assault even if they have sex
      with a condom or while having a low (or undetectable) viral load, they had no
      intent to transmit HIV, and no transmission occurred. In 2013, six distinguished
      Canadian HIV scientists and clinicians took ground-breaking action to advance
      justice by co-authoring the "Canadian consensus statement on HIV and its
      transmission in the context of the criminal law." This effort was born out of the
      belief that the application of criminal law to HIV non-disclosure was being
      driven by a poor appreciation of the science of HIV. More than 75 HIV scientists
      and clinicians Canada-wide have now endorsed the statement, agreeing that "[they]
      have a professional and ethical responsibility to assist those in the criminal
      justice system to understand and interpret current medical and scientific
      evidence regarding HIV." As some 61 countries have adopted laws that specifically
      allow for HIV criminalization, and prosecutions for HIV non-disclosure, exposure
      and transmission have been reported in at least 49 countries, the authors hope
      that others around the world will take similar action. 

PMID- 26194346
TI  - Homocysteine and the risk of age-related macular degeneration: a systematic
      review and meta-analysis.
AB  - Contrasting results have been reported regarding the associations between plasma
      total homocysteine (tHcy) and B vitamin levels and age-related macular
      degeneration (AMD) risk. Thus, we aimed to systematically evaluate these
      associations. Relevant case control studies in English were identified via a
      thorough search of the PubMed, Medline, and Embase databases from inception to
      June 2014. The results were pooled using Review Manager 5.2.1. Eleven studies
      (including 1072 cases and 1202 controls) were eligible for analysis of tHcy
      levels; additionally, 3 studies (including 152 cases and 98 controls) were
      eligible for analysis of folic acid and vitamin B12 levels. The cumulative
      results demonstrated that the plasma tHcy level among the AMD cases was 2.67
      MUmol/L (95% confidence interval [CI], 1.60-3.74) higher than that among the
      controls. In contrast, the vitamin B12 level among the AMD cases was 64.16 pg/mL
      (95% CI, 19.32-109.00) lower than that among the controls. Subgroup analyses
      showed that the folic acid level was 1.66 ng/mL (95% CI, 0.10-3.21) lower for the
      wet type. Together, the results demonstrated that AMD is associated with elevated
      tHcy levels and decreased vitamin B12 levels. Plasma tHcy may act as a modulator
      of the risk for AMD based on the current evidence.

PMID- 26194347
TI  - Nrf2 is a potential prognostic marker and promotes proliferation and invasion in
      human hepatocellular carcinoma.
AB  - BACKGROUND: Nuclear factor E2-related factor 2 (Nrf2 or NFE2L2) is abundantly
      expressed in cancer cells and relates to proliferation, invasion, and
      chemoresistance. Our early observations also found that expression of Nrf2 was up
      regulated in kinds of cancer including human hepatocellular carcinoma (HCC)
      cells. But there are limited reports about the expression, significance, function
      of Nrf2 in HCC. METHODS: First, Nrf2 expression was analyzed in HCC cell lines
      and tumor samples. Then, the relationship of Nrf2 with clinicopathological
      factors and survival were analyzed. Further, the effect of Nrf2 on cell
      proliferation, apoptosis, and metastasis was examined in vitro by modulating
      expression of Nrf2 through specific shRNA or expression plasmid. Last, the
      potential mechanisms were also investigated. RESULTS: Nrf2 was up-regulated in
      HCC, and expression of Nrf2 was correlated with tumor differentiation,
      metastasis, and tumor size. Univariate and multivariate analyses indicated that
      high Nrf2 expression might be a poor prognostic factor. Further studies
      demonstrated that inhibition of Nrf2 expression inhibited proliferation by
      inducing apoptosis and repressed invasion, and up-regulation of Nrf2 expression
      resulted in opposite phenotypes. Moreover, there are positive correlation between
      Nrf2 expression and that of Bcl-xL and MMP-9. CONCLUSION: Nrf2 is a potential
      prognostic marker and promotes proliferation and invasion in human hepatocellular
      carcinoma partly through regulating expression of Bcl-xL and MMP-9.

PMID- 26194349
TI  - Assorted morphosynthesis: access to multi-faceted nano-architectures from a super
      responsive dual pi-functional amphiphilic construct.
AB  - An electronically segmented amphiphile was created by conjugating two pi
      functional units hydroxyquinoline and naphthalenediimide (HQ/NDI) for the first
      time. The differential electrostatic potential of the pi-surfaces, H-bonding
      units, etc. trigger a manifold response and direct the assembly of a unique
      collection of seven diverse nano-architectures. Chiral assembly, distinct classes
      of fibers, 3-D sheets, and metallo-spheres/fibrils with MUM levels of
      Co/Cu/Zn(ii) ions emerged from this new approach of assorted morphosynthesis
      under ambient conditions. 

PMID- 26194350
TI  - Distribution of health literacy strengths and weaknesses across socio-demographic
      groups: a cross-sectional survey using the Health Literacy Questionnaire (HLQ).
AB  - BACKGROUND: Recent advances in the measurement of health literacy allow
      description of a broad range of personal and social dimensions of the concept.
      Identifying differences in patterns of health literacy between population sub
      groups will increase understanding of how health literacy contributes to health
      inequities and inform intervention development. The aim of this study was to use
      a multi-dimensional measurement tool to describe the health literacy of adults in
      urban and rural Victoria, Australia. METHODS: Data were collected from clients (n
      = 813) of 8 health and community care organisations, using the Health Literacy
      Questionnaire (HLQ). Demographic and health service data were also collected.
      Data were analysed using descriptive statistics. Effect sizes (ES) for
      standardised differences in means were used to describe the magnitude of
      difference between demographic sub-groups. RESULTS: Mean age of respondents was
      72.1 (range 19-99) years. Females comprised 63% of the sample, 48% had not
      completed secondary education, and 96% reported at least one existing health
      condition. Small to large ES were seen for mean differences in HLQ scales between
      most demographic groups. Compared with participants who spoke English at home,
      those not speaking English at home had much lower scores for most HLQ scales
      including the scales 'Understanding health information well enough to know what
      to do' (ES -1.09 [95% confidence interval (CI) -1.33 to -0.84]), 'Ability to
      actively engage with healthcare providers' (ES -1.00 [95% CI -1.24, -0.75]), and
      'Navigating the healthcare system' (ES -0.72 [95% CI -0.97, -0.48]). Similar
      patterns and ES were seen for participants born overseas compared with those born
      in Australia. Smaller ES were seen for sex, age group, private health insurance
      status, number of chronic conditions, and living alone. CONCLUSIONS: This study
      has revealed some large health literacy differences across nine domains of health
      literacy in adults using health services in Victoria. These findings provide
      insights into the relationship between health literacy and socioeconomic position
      in vulnerable groups and, given the focus of the HLQ, provide guidance for the
      development of equitable interventions.

PMID- 26194351
TI  - A population-level study of place of death and associated factors in Sweden.
AB  - AIMS: The aims of this study were to examine, on a population level, where people
      die in Sweden, and to investigate associations between place of death and
      underlying cause of death, socioeconomic and environmental characteristics, with
      a particular interest in people dying from life-limiting conditions typically in
      need of palliative care. METHODS: This population-level study is based on death
      certificate data for all deceased individuals in Sweden in 2012, with a
      registered place of death (n=83,712). Multivariable logistic regression was
      performed to investigate associations between place of death and individual,
      socioeconomic and environmental characteristics. RESULTS: The results show that,
      in 2012, 42.1% of all deaths occurred in hospitals, 17.8% occurred at home and
      38.1% in nursing home facilities. Individuals dying of conditions indicative of
      potential palliative care needs were less likely to die in hospital than those
      dying of other conditions (OR = 0.73; 95% CI = 0.70-0.77). Living at home in
      urban areas was associated with higher likelihood of dying in hospital or in a
      nursing home (OR = 1.04 and 1.09 respectively). Educational attainment and
      marital status were found to be somewhat associated with the place of death.
      CONCLUSIONS: The majority of deaths in Sweden occur in institutional settings,
      with comparatively larger proportions of nursing home deaths than most countries.
      Associations between place of death and other variables point to inequalities in
      availability and/or utilization of health services at the end of life.

PMID- 26194352
TI  - Emerging evidence that the ban on asbestos use is reducing the occurrence of
      pleural mesothelioma in Sweden.
AB  - AIMS: Several countries have banned the use of asbestos. The future health
      impacts of previous use have been modeled but there are to our knowledge no
      convincing studies showing a decreased occurrence of asbestos-related diseases
      due to a ban. The aim of our study was to estimate the effects of the ban and
      other measures to decrease the use of asbestos in Sweden. METHODS: The effect was
      measured through comparing the incidence of pleural malignant mesothelioma in
      birth cohorts who started to work before and after the decrease in the use of
      asbestos, i.e. in mid-1970s. Cases were identified through the Swedish Cancer
      Registry and the analysis was restricted to persons born in Sweden. RESULTS: Men
      and women born 1955-79 had a decreased risk of malignant pleural mesothelioma
      compared to men and women born 1940-49 (RR 0.16, 95% CI 0.11-0.25; and RR 0.47,
      95% CI 0.23-0.97 respectively). The decreased use of asbestos prevented each year
      about 10 cases in men and two cases in women below the age of 57 years in 2012.
      CONCLUSIONS: The ban and decreased use of asbestos in Sweden can be measured
      today in birth cohorts that started their working career after the decrease.

PMID- 26194353
TI  - Health care services and maternal education in South Africa.
AB  - AIMS: The aim of the study is to investigate the influence of maternal education
      on the utilization of maternal health care services in selected areas of the
      Eastern Cape. Moreover, the study's aim also is to examine the reasons for non
      use as well as determinants and levels of maternal health care utilization.
      METHODS: From the 422 participants sampled, 345 fully completed questionnaires
      were returned and included in the analysis. The study used multilevel analyses.
      The dependent variables included antenatal care, delivery care, and postnatal
      care within 2 months after birth. The independent variables were socioeconomic
      and demographic factors selected based on literature on the subject. RESULTS: Use
      of antenatal and delivery care services was high in the study areas, but
      postnatal check-ups were reported below 50%. The majority of the women (50%)
      reported that the ambulance arrived too late, and, as such, they did not use
      health facilities when giving birth. Women with four or more children use
      antenatal and delivery care less than women with one child, while women with four
      or more children use postnatal care more than women with just one child.
      CONCLUSIONS: This study will be immense useful for the policy-makers, public
      health research managers and concerned health care decision-makers.

PMID- 26194355
TI  - Prostanoids are not involved in postocclusive reactive hyperaemia in human skin.
AB  - Several mediators contribute to postocclusive reactive hyperaemia (PORH) in the
      skin, including sensory nerves and endothelium-derived hyperpolarizing factors.
      The main objective of this study was to investigate the specific involvement of
      prostanoids in human skin PORH. We tested the effect of the inhibition of cyclo
      oxygenases (COX) by 4 mm ketoprofen, infused through microdialysis fibers
      inserted into the healthy volunteers forearm skin, following 5 min brachial
      artery occlusion. Skin microvascular blood flux was recorded using two
      dimensional Laser Speckle Contrast Imaging. Maximal cutaneous vascular
      conductance (CVCmax ) was obtained following the perfusion of 29 mm sodium
      nitroprusside. A systematic review of the effects of COX inhibitors on skin peak
      PORH was also performed. We observed no significant difference between ketoprofen
      and placebo for the PORH peak (78 +/- 8 and 71 +/- 19% CVCmax , respectively) and
      area under the curve (2951 +/- 721 and 2490 +/- 936% CVCmax .s). A meta-analysis
      showed a substantial heterogeneity between studies, with overall a neutral effect
      of COX inhibition on peak PORH. Cyclo-oxygenase inhibition does not alter skin
      PORH, suggesting no involvement of prostanoids in cutaneous postocclusive
      vasodilatation in healthy humans. 

PMID- 26194354
TI  - Chronic Rho-kinase inhibition improves left ventricular contractile dysfunction
      in early type-1 diabetes by increasing myosin cross-bridge extension.
AB  - BACKGROUND: Impaired actin-myosin cross-bridge (CB) dynamics correlate with
      impaired left ventricular (LV) function in early diabetic cardiomyopathy (DCM).
      Elevated expression and activity of Rho kinase (ROCK) contributes to the
      development of DCM. ROCK targets several sarcomeric proteins including myosin
      light chain 2, myosin binding protein-C (MyBP-C), troponin I (TnI) and troponin T
      that all have important roles in regulating CB dynamics and contractility of the
      myocardium. Our aim was to examine if chronic ROCK inhibition prevents impaired
      CB dynamics and LV dysfunction in a rat model of early diabetes, and whether
      these changes are associated with changes in myofilament phosphorylation state.
      METHODS: Seven days post-diabetes induction (65 mg/kg ip, streptozotocin),
      diabetic rats received the ROCK inhibitor, fasudil (10 mg/kg/day ip) or vehicle
      for 14 days. Rats underwent cardiac catheterization to assess LV function
      simultaneous with X-ray diffraction using synchrotron radiation to assess in situ
      CB dynamics. RESULTS: Compared to controls, diabetic rats developed mild systolic
      and diastolic dysfunction, which was attenuated by fasudil. End-diastolic and
      systolic myosin proximity to actin filaments were significantly reduced in
      diabetic rats (P < 0.05). In all rats there was an inverse correlation between
      ROCK1 expression and the extension of myosin CB in diastole, with the lowest ROCK
      expression in control and fasudil-treated diabetic rats. In diabetic and fasudil
      treated diabetic rats changes in relative phosphorylation of TnI and MyBP-C were
      not significant from controls. CONCLUSIONS: Our results demonstrate a clear role
      for ROCK in the development of LV dysfunction and impaired CB dynamics in early
      DCM.

PMID- 26194357
TI  - Question 2: what are the risk factors for antibiotic resistant Gram-negative
      bacteraemia in children with cancer?

PMID- 26194356
TI  - RiTE database: a resource database for genus-wide rice genomics and evolutionary
      biology.
AB  - BACKGROUND: Comparative evolutionary analysis of whole genomes requires not only
      accurate annotation of gene space, but also proper annotation of the repetitive
      fraction which is often the largest component of most if not all genomes larger
      than 50 kb in size. RESULTS: Here we present the Rice TE database (RiTE-db)--a
      genus-wide collection of transposable elements and repeated sequences across 11
      diploid species of the genus Oryza and the closely-related out-group Leersia
      perrieri. The database consists of more than 170,000 entries divided into three
      main types: (i) a classified and curated set of publicly-available repeated
      sequences, (ii) a set of consensus assemblies of highly-repetitive sequences
      obtained from genome sequencing surveys of 12 species; and (iii) a set of full
      length TEs, identified and extracted from 12 whole genome assemblies.
      CONCLUSIONS: This is the first report of a repeat dataset that spans the majority
      of repeat variability within an entire genus, and one that includes complete
      elements as well as unassembled repeats. The database allows sequence browsing,
      downloading, and similarity searches. Because of the strategy adopted, the RiTE
      db opens a new path to unprecedented direct comparative studies that span the
      entire nuclear repeat content of 15 million years of Oryza diversity.

PMID- 26194358
TI  - Paediatric emergency medicine consultant provision in the UK: are we there yet?

PMID- 26194359
TI  - Coeliac disease: the association between quality of life and social support
      network participation.
AB  - BACKGROUND: There is little information available on the use of social support
      systems for patients with coeliac disease (CD). We performed a cross-sectional
      study aiming to examine the association between participation in different types
      of social support networks and quality of life (QOL) in adults with CD. METHODS:
      A survey including a validated CD specific QOL instrument was administered online
      and in-person to adults with CD who were following a gluten-free diet.
      Participation in social support networks (type, frequency and duration) were
      assessed. RESULTS: Among the 2138 participants, overall QOL scores were high,
      averaging 68.9 out of 100. Significant differences in QOL scores were found for
      age, length of time since diagnosis and level of education. Most (58%) reported
      using no social support networks. Of the 42% reporting use of social support
      networks (online 17.9%, face-to-face 10.8% or both 12.8%), QOL scores were higher
      for those individuals who used only face-to-face social support compared to only
      online support (72.6 versus 66.7; P < 0.0001). A longer duration of face-to-face
      social support use was associated with higher QOL scores (P < 0.0005). By
      contrast, a longer duration and increased frequency of online social support use
      was associated with lower QOL scores (P < 0.03). CONCLUSIONS: Participation in
      face-to-face social support networks is associated with greater QOL scores
      compared to online social support networks. These findings have potential
      implications for the management of individuals with CD. Emphasis on face-to-face
      support may improve long-term QOL and patient outcomes.

PMID- 26194360
TI  - Preservation of an intra-pancreatic hepatic artery during pancreato-duodenectomy.

PMID- 26194361
TI  - Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on
      the SCOTROC1 trial.
AB  - Carboplatin/taxane combination is first-line therapy for ovarian cancer. However,
      patients can encounter treatment delays, impaired quality of life, even death
      because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene
      study was conducted to assess potential association of genetic variants with GI
      toxicity in 808 patients who received carboplatin/taxane in the Scottish
      Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into
      discovery and validation cohorts consisting of 404 patients each. Clinical
      covariates and genetic variants associated with grade III/IV GI toxicity in
      discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI
      toxicity was significantly associated with seven single-nucleotide polymorphisms
      in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at
      1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity
      (P<0.01). Variants in the VEGF gene were marginally associated with survival
      time. Our data provide potential targets for modulation/inhibition of GI toxicity
      in ovarian cancer patients.

PMID- 26194362
TI  - Paradoxical psoriasiform reactions to anti-TNFalpha drugs are associated with
      genetic polymorphisms in patients with psoriasis.
AB  - Paradoxical psoriasiform reactions to anti-tumor necrosis factor alpha (TNFalpha)
      agents have been described. We aimed to study the association between these
      reactions and polymorphisms in genes previously associated with psoriasis or
      other autoimmune diseases. A total of 161 patients with plaque-type psoriasis
      treated with anti-TNFalpha drugs were genotyped for 173 single-nucleotide
      polymorphisms (SNPs) using the Illumina Veracode genotyping platform. Among the
      161 patients, 25 patients developed a paradoxical psoriasiform reaction
      consisting of a change in morphology, mostly to guttate psoriasis (88%). These
      lesions developed 9.20+/-13.52 months after initiating treatment, mainly with
      etanercept (72%). Psoriasis type and a Psoriasis Area and Severity Index (PASI)
      75 response to treatment were not associated with lesions. Multivariate logistic
      regression revealed that five SNPs (rs11209026 in IL23R, rs10782001 in FBXL19,
      rs3087243 in CTLA4, rs651630 in SLC12A8 and rs1800453 in TAP1) were associated
      with paradoxical reactions. This is the first study to show an association
      between genetic polymorphisms and paradoxical reactions in patients with
      psoriasis treated with anti-TNFalpha drugs.The Pharmacogenomics Journal advance
      online publication, 21 July 2015; doi:10.1038/tpj.2015.53.

PMID- 26194363
TI  - HPMA Copolymer-Conjugated Pirarubicin in Multimodal Treatment of a Patient with
      Stage IV Prostate Cancer and Extensive Lung and Bone Metastases.
AB  - Nanomedicine allows achievement of tumor-selective drug delivery because of the
      enhanced permeability and retention (EPR) effect of solid tumors. We report here
      the first clinical application of a new agent-HPMA copolymer-conjugated
      pirarubicin (P-THP)-with a molecular size of about 8 nm, or 38.5 kDa. A patient
      had advanced prostate cancer with multiple metastases in the lung, pelvis, femur,
      and perhaps the sacrum. In April 2013, this 60-year-old patient started treatment
      with leuprorelin and estradiol, which continued until July 2014, but the patient
      became refractory to this treatment. So the patient underwent proton beam
      radiotherapy targeted to the primary prostate cancer, and P-THP was administered
      for numerous metastatic tumor nodules concomitantly with radiotherapy. This
      combination therapy had remarkable results, with complete remission of multiple
      metastases in the lung and bone. The prostate-specific antigen (PSA) value was
      decreased from about 1000 ng/mL on April 30, 2013, to about 100 ng/mL on June 24,
      2013, with hormone therapy, but rose again to 964.2 ng/mL and then to 1472 ng/mL
      in July 2013, during leuprorelin administration. P-THP treatment administered
      concomitantly with proton beam irradiation was started in August 2013. The PSA
      value was decreased to 102 ng/mL on August 26, 2013, and then to 0.971 ng/mL on
      October 8, 2013, and 0.277 ng/mL on January 15, 2015. The P-THP doses ranged from
      30 to 75 mg of free THP equivalent/patient every 2-3 weeks without signs of
      serious toxicity, such as cardiovascular side effects or a reduction in quality
      of life. No evidence of relapse was found more than 20 months after P-THP
      administration. This case demonstrates the value of hydrazone-bonded polymeric
      drugs in multimodal therapy.

PMID- 26194364
TI  - [Transcatheter aortic valve implantation (TAVI): Current perspectives].
AB  - Transcatheter aortic valve implantation (TAVI) has evolved as the treatment
      modality of choice for elderly patients with symptomatic severe aortic stenosis
      who are at high risk for surgery. More than 10,000 TAVI procedures were
      undertaken in Germany during 2014.A mortality benefit has been shown for TAVI
      compared with conservative treatment in patients deemed inoperable, and the
      procedure was proven to be at least non-inferior to surgical aortic valve
      replacement in high-risk patients. Through improvements in preprocedural imaging
      and in valve technology as well as increasing operator and surgical team
      experience, TAVI has developed rapidly in the past few years. Complication rates
      declinded considerably and the latest study results even suggest a superiority of
      TAVI to surgical valve replacement in patients at intermediate operative risk.
      Nevertheless, the challenge to avoid procedure-specific complications influencing
      the outcome still remains. Therefore, making an individual decision about the
      approach and the valve prosthesis in an interdisciplinary heart team consisting
      of a cardiologist and a cardiac surgeon is indispensable for guaranteeing the
      best therapy for the patient.Considering the rapid developments and procedural
      improvements in this field, randomized trials are required to assess whether the
      indication for TAVI may be extended to patients at lower perioperative risk in
      the future. 

PMID- 26194365
TI  - Serological evidence for the circulation of flaviviruses in seabird populations
      of the western Indian Ocean.
AB  - Birds play a central role in the epidemiology of several flaviviruses of concern
      for public and veterinary health. Seabirds represent the most abundant and
      widespread avifauna in the western Indian Ocean and may play an important role as
      host reservoirs and spreaders of arthropod-borne pathogens such as flaviviruses.
      We report the results of a serological investigation based on blood samples
      collected from nine seabird species from seven islands in the Indian Ocean. Using
      a commercial competitive enzyme-linked immunosorbent assay directed against the
      prototypic West Nile flavivirus, antibodies against flaviviruses were detected in
      the serum of 47 of the 855 seabirds tested. They were detected in bird samples
      from three islands and from four bird species. Seroneutralization tests on adults
      and chicks suggested that great frigatebirds (Fregata minor) from Europa were
      infected by West Nile virus during their non-breeding period, and that Usutu
      virus probably circulated within bird colonies on Tromelin and on Juan de Nova.
      Real-time polymerase chain reactions performed on bird blood samples did not
      yield positive results precluding the genetic characterization of flavivirus
      using RNA sequencing. Our findings stress the need to further investigate
      flavivirus infections in arthropod vectors present in seabird colonies. 

PMID- 26194366
TI  - Second Primary Cancer after Diagnosis and Treatment of Cervical Cancer.
AB  - PURPOSE: This study was conducted to investigate the incidence and survival
      outcomes of second primary cancers after the diagnosis of cervical cancer.
      MATERIALS AND METHODS: Data from the Korea Central Cancer Registry between 1993
      and 2010 were reviewed and analyzed. Standardized incidence ratios (SIRs) of
      second primary cancers among women with cervical cancer were analyzed. Kaplan
      Meier survival curves were constructed for cervical cancer patients with or
      without a second primary cancer. RESULTS: Among 72,805 women with cervical
      cancer, 2,678 (3.68%) developed a second primary cancer within a mean follow-up
      period of 7.34 years. The overall SIR for a second cancer was 1.08 (95%
      confidence interval, 1.04 to 1.12). The most frequent sites of second primary
      cancers were the vagina, bone and joints, vulva, anus, bladder, lung and
      bronchus, corpus uteri, and esophagus. However, the incidence rates of four
      second primary cancers (breast, rectum, liver, and brain) were decreased. The 5
      year and 10-year overall survival rates were 78.3% and 72.7% in all women with
      cervical cancer, and for women with a second primary cancer, these rates were
      83.2% and 65.5% from the onset of cervical cancer and 54.9% and 46.7% from the
      onset of the second primary cancer, respectively. CONCLUSION: The incidence rates
      of second primary cancers were increased in women with cervical cancer compared
      to the general population, with the exception of four decreasing cancers. The 10
      year overall survival rates were decreased in cervical cancer patients with a
      second primary cancer.

PMID- 26194367
TI  - Do Biliary Complications after Hypofractionated Radiation Therapy in
      Hepatocellular Carcinoma Matter?
AB  - PURPOSE: The purpose of this study is to evaluate the efficacy of
      hypofractionated radiation therapy (RT) in the treatment of unresectable
      hepatocellular carcinoma (HCC) after failure of transarterial chemoembolization
      (TACE) or in cases of refractory HCC, and to investigate biliary complications
      after hypofractionated RT. MATERIALS AND METHODS: We retrospectively enrolled
      patients with unresectable, TACE-unresponsive, or refractory HCC treated with
      hypofractionated RT between July 2006 and December 2012. The perihilar region was
      defined as the 1-cm area surrounding the right, left, and the common hepatic
      duct, including the gallbladder and the cystic duct. Significant elevation of
      total bilirubin was defined as an increase of more than 3.0 mg/dL, and more than
      two times that of the previous level after completion of RT. RESULTS: Fifty
      patients received hypofractionated RT and 27 (54%) had a tumor located within the
      perihilar region. The median follow-up period was 24.7 months (range, 4.3 to 95.5
      months). None of the patients developed classic radiation disease symptoms, but
      four patients (8%) showed significant elevation of total bilirubin within 1 year
      after RT. During follow-up, 12 patients (24%) developed radiologic biliary
      abnormalities, but only two patients had toxicities requiring intervention.
      Estimated local progression-free survival, progression-free survival, and overall
      survival of the patients at 3-year post-hypofractionated RT were 89.7%, 11.2%,
      and 57.4%, respectively. CONCLUSION: Biliary complications associated with a
      higher dose exposure of hypofractionated RT were minimal, even in the perihilar
      region. Hypofractionated RT provided excellent local control and may be a
      valuable option for treatment of unresectable cases of TACE-unresponsive or
      refractory HCC.

PMID- 26194368
TI  - Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Tissue Type
      Involving the Dura.
AB  - Primary central nervous system marginal zone B-cell lymphoma (MZBCL) is very
      rare, with only a few reported cases worldwide. It has an indolent disease course
      with high cure potential. We experienced a rare case of dural MZBCL of mucosa
      associated lymphoid tissue (MALT) in a 69-year-old man who presented with
      headache. A magnetic resonance imaging scan of brain showed a 1.9*3.6-cm-sized
      extra-axial mass with a broad based dural attachment to the anterosuperior aspect
      of the falx cerebri, radiographically consistent with meningioma. Surgical
      resection yielded a MZBCL of the MALT type. Histopathology revealed a
      lymphoplasmacytic infiltration of the dura, and immunohistochemical study showed
      a B-cell phenotype with CD20, bcl-2, MUM-1, Ki-67 positive. He was treated with
      chemotherapy after complete surgical resection and remained free of disease at 30
      months after chemotherapy. MALT lymphoma must be considered in the differential
      diagnosis in patients presenting radiographically with meningioma. 

PMID- 26194370
TI  - Prognostic Value of Log Odds of Positive Lymph Nodes after Radical Surgery
      Followed by Adjuvant Treatment in High-Risk Cervical Cancer.
AB  - PURPOSE: The purpose of this study is to compare the prognostic efficacy of the
      number and location of positive lymph nodes (LN), LN ratio (LNR), and log odds of
      positive LNs (LODDs) in high-risk cervical cancer treated with radical surgery
      and adjuvant treatment. MATERIALS AND METHODS: Fifty high-risk patients who
      underwent radical hysterectomy and pelvic node dissection followed by adjuvant
      treatment were analyzed retrospectively. The patients had International
      Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIB. Upper LN is defined
      as common iliac or higher LN, and LNR is the ratio of positive LNs to harvested
      LNs. LODDs is log odds between positive LNs and negative LNs. Radiotherapy was
      delivered to the whole pelvis with median 50.4 Gy/28 Fx+/- to the para-aortic
      regions. Platinum-based chemotherapy was used in most patients (93%). The median
      follow-up duration was 80 months. RESULTS: The 5-year disease-free survival (DFS)
      rate was 76.1%, and the overall survival (OS) rate was 86.4%. Treatment failure
      occurred in 11 patients, and distant failure (DF) was the dominant pattern
      (90.9%). In univariate analysis, significantly lower DFSwas observed in patients
      with perineural invasion, >= 2 LN metastases, LNR >= 10%, upper LN metastasis,
      and >= -1.05 LODDs. In multivariate analysis, >= -1.05 LODDs was the only
      significant factor for DFS (p=0.011). Of patients with LODDs >= -1.05, 40.9%
      experienced DF. LODDs was the only significant prognostic factor for OS as well
      (p=0.006). CONCLUSION: LODDs >= -1.05 was the only significant prognostic factor
      for both DFS and OS. In patients with LODDs >= -1.05, intensified chemotherapy
      might be required, considering the high rate of DF.

PMID- 26194369
TI  - Population-Based Regional Cancer Incidence in Korea: Comparison between Urban and
      Rural Areas.
AB  - PURPOSE: The purpose of this study is to investigate differences in organ
      specific cancer incidence according to the region and population size in Korea.
      MATERIALS AND METHODS: We reviewed the data of the cancer registration program of
      Gyeongnam Regional Cancer Center between 2008 and 2011. Age-standardized rates of
      cancer incidence were analyzed according to population size of the region and
      administrative zone. RESULTS: Incidence of thyroid cancer has been increasing
      rapidly in both urban and rural areas. However, the thyroid cancer incidence was
      much lower in rural areas than in urban areas and megalopolis such as Seoul.
      Gastric cancer was relatively more common in rural areas, in megalopolis near the
      sea (Ulsan, Busan, and Incheon), and other southern provinces (Chungcheongnam-do,
      Gyeongsangbuk-do, and Gyeongsangnam-do). A detailed analysis in Gyeongsangnam-do
      revealed that rural areas have relatively low incidence of thyroid and colorectal
      cancer, and relatively high incidence of gastric and lung cancer compared to
      urban areas. CONCLUSION: This study suggests that there are some differences in
      cancer incidence by population size. Thyroid and colorectal cancer incidence was
      increasing, and gastric and lung cancer was slightly decreasing in urban areas,
      whereas gastric and lung cancer incidence still remains high in rural areas.

PMID- 26194371
TI  - Tumor Volume Reduction Rate during Adaptive Radiation Therapy as a Prognosticator
      for Nasopharyngeal Cancer.
AB  - PURPOSE: The purpose of this study is to evaluate the prognostic significance of
      the tumor volume reduction rate (TVRR) measured during adaptive definitive
      radiation therapy (RT) for nasopharyngeal cancer (NPC). MATERIALS AND METHODS: We
      reviewed the RT records of 159 NPC patients treated with definitive RT with or
      without concurrent chemotherapy between January 2006 and February 2013. Adaptive
      re-planning was performed in all patients at the third week of RT. The pre- and
      mid-RT gross tumor volumes (GTVs) of the primary tumor and the metastatic lymph
      nodes were measured and analyzed for prognostic implications. RESULTS: After a
      median follow-up period of 41.5 months (range, 11.2 to 91.8 months) for
      survivors, there were 43 treatment failures. The overall survival and progression
      free survival (PFS) rates at 5 years were 89.6% and 69.7%, respectively. The mean
      pre-RT GTV, mid-RT GTV, and TVRR were 45.9 cm(3) (range, 1.5 to 185.3 cm(3)),
      26.7 cm(3) (1.0 to 113.8 cm(3)), and -41.9% (range, -87% to 78%), respectively.
      Patients without recurrence had higher TVRR than those with recurrence (44.3% in
      the no recurrence group vs. 34.0% in the recurrence group, p=0.004), and those
      with TVRR > 35% achieved a significantly higher rate of PFS at 5 years (79.2% in
      TVRR > 35% vs. 53.2% in TVRR <= 35%; p < 0.001). In multivariate analysis, TVRR
      was a significant factor affecting PFS (hazard ratio, 2.877; 95% confidence
      interval, 1.555 to 5.326; p=0.001). CONCLUSION: TVRR proved to be a significant
      prognostic factor in NPC patients treated with definitive RT, and could be used
      as a potential indicator for early therapeutic modification during the RT course.

PMID- 26194372
TI  - Long-Term Low-Dose Aspirin Use Reduces Gastric Cancer Incidence: A Nationwide
      Cohort Study.
AB  - PURPOSE: The aim of this study was to investigate whether aspirin use can reduce
      the incidence of gastric cancer in patients with hypertension or type 2 diabetes.
      MATERIALS AND METHODS: A total of 200,000 patients with hypertension or type 2
      diabetes were randomly selected from the Korean National Health Insurance claim
      database. Of these, 3,907 patients who used 100 mg of aspirin regularly (regular
      aspirin users) and 7,808 patients who did not use aspirin regularly (aspirin non
      users) were selected at a frequency of 1:2, matched by age, sex, comorbid
      illnesses (type 2 diabetes and hypertension), and observation periods. The
      incidence of gastric cancer in this cohort was then assessed during the
      observation period of 2004 to 2010. RESULTS: In the matched cohort, the incidence
      rates of gastric cancer were 0.8% (31/3,907) for regular aspirin users and 1.1%
      (86/7,808) for aspirin non-users, but the cumulative incidence rates were not
      significantly different between groups (p=0.116, log-rank test). However, in
      multivariate analysis, regular aspirin users had a reduced risk of gastric cancer
      (adjusted hazard ratio [aHR], 0.71; 95% confidential interval [CI], 0.47 to 1.08;
      p=0.107). Duration of aspirin use showed significant association with reduction
      of gastric cancer risk (aHR for each year of aspirin use, 0.85; 95% CI, 0.73 to
      0.99; p=0.044), particularly in patients who used aspirin for more than 3 years
      (aHR, 0.40; 95% CI, 0.16 to 0.98; p=0.045). CONCLUSION: Long-term low-dose
      aspirin use was associated with reduced gastric cancer risk in patients with
      hypertension or type 2 diabetes.

PMID- 26194373
TI  - Impact of Job Status on Accessibility of Cancer Screening.
AB  - PURPOSE: Cancer is a leading cause of death worldwide with approximately 75,000
      cancer deaths in Korea alone in 2013. Cancer screening is an important method of
      prevention; however, only 63.4% of Koreans sought cancer screening in 2012 even
      though it was widely offered at no cost. We focused on part time workers because
      they often experience job instability and relative discrimination. Therefore, we
      investigated the correlation between job status and cancer screening. MATERIALS
      AND METHODS: Data from the 2013 Korea National Health and Nutrition Examination
      Survey (KNHANES) were used for selection of individuals who participated in the
      national cancer screening program. A total of 1,326 wage earners were selected
      for our study. The association between cancer screening and part time job status
      was examined using logistic regression models. RESULTS: Of the 1,326 individuals
      selected for the study, 869 (64.5%) had participated in the cancer screening
      program; among these, 421 (48.4%) were part time workers and 448 (51.6%) were
      full time workers. Lower prevalence of cancer screening was observed for part
      time workers compared to full time workers (odds ratio, 0.72; confidence
      interval, 0.53 to 1.00; p=0.0495). Factors including age, marital status, private
      insurance, chronic disease, smoking, and residential area emerged as showed
      significant association with participation in screening programs. CONCLUSION: We
      found that part time workers had difficulty participating in prevention programs.
      Change in the workplace environment as well as development of positive social
      programs targeted to part time workers is necessary in order to encourage
      participation of part time workers in prevention programs.

PMID- 26194374
TI  - Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in
      Patients with Metastatic Breast Cancer.
AB  - PURPOSE: This study analyzed the role of plasma biomarkers for TSU-68 in a
      previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in
      patients with metastatic breast cancer. MATERIALS AND METHODS: A total of 77
      patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39
      in the docetaxel alone arm). Blood samples were collected prior to the start of
      each cycle, and vascular endothelial growth factor (VEGF), platelet-derived
      growth factor (PDGF)-AA, -AB, -BB, fibroblast growth factor, M30, C-reactive
      protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked
      immunosorbent assay. The primary endpoint was progression-free survival (PFS).
      RESULTS: In patients with baseline PDGF-AA >= median, median PFS was
      significantly worse in the TSU-68 plus docetaxel group than in the docetaxel
      alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS
      benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0
      months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS
      showed significant association with fold changes in CRP (p=0.001), IL-6 (p <
      .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle.
      CONCLUSION: Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6
      levels were predictive for the efficacy of TSU-68.

PMID- 26194376
TI  - A plan to protect the world--and save WHO.

PMID- 26194375
TI  - VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid
      Cystic Carcinoma.
AB  - PURPOSE: The purpose of this study was to evaluate potential prognostic factors
      in patients with adenoid cystic carcinoma (ACC). MATERIALS AND METHODS: A total
      of 68 patients who underwent curative surgery and had available tissue were
      enrolled in this study. Their medical records and pathologic slides were reviewed
      and immunohistochemistry for basic fibroblast growth factor, fibroblast growth
      factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet
      derived growth factor receptor beta, vascular endothelial growth factor (VEGF),
      and Ki-67 was performed. Univariate and multivariate analysis was performed for
      determination of disease-free survival (DFS) and overall survival (OS). RESULTS:
      In univariate analyses, primary site of nasal cavity and paranasal sinus
      (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically
      significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032),
      high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were
      poor prognostic factors. In multivariate analyses, primary site of nasal cavity
      and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were
      independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and
      Ki-67 (p=0.011) showed independent association with poor OS. CONCLUSION: High
      expression of VEGF and Ki-67 were independent poor prognostic factors for OS in
      ACC.

PMID- 26194377
TI  - The Greek health crisis.

PMID- 26194378
TI  - Cuba: defeating AIDS and advancing global health.

PMID- 26194379
TI  - The Global Financing Facility: country investments for every woman, adolescent,
      and child.

PMID- 26194380
TI  - Future inequalities in life expectancy in England and Wales.

PMID- 26194383
TI  - Tackling the UK's alcohol problems.

PMID- 26194385
TI  - Beyond Bazalgette: 150 years of sanitation.

PMID- 26194386
TI  - Michael Francis Oliver.

PMID- 26194387
TI  - Neonatal vitamin A: time to move on?

PMID- 26194388
TI  - Strategies to prevent future Ebola epidemics.

PMID- 26194389
TI  - Neonatal vitamin A: time to move on?

PMID- 26194390
TI  - Neonatal vitamin A: time to move on?

PMID- 26194391
TI  - Neonatal vitamin A: time to move on?

PMID- 26194392
TI  - Isotonic fluid for intravenous hydration maintenance in children.

PMID- 26194393
TI  - Isotonic fluid for intravenous hydration maintenance in children.

PMID- 26194394
TI  - Department of Error.

PMID- 26194395
TI  - Department of Error.

PMID- 26194396
TI  - Department of Error.

PMID- 26194397
TI  - Isotonic fluid for intravenous hydration maintenance in children - Authors'
      reply.

PMID- 26194398
TI  - Dieckol, a phlorotannin of Ecklonia cava, suppresses IgE-mediated mast cell
      activation and passive cutaneous anaphylactic reaction.

PMID- 26194400
TI  - Stevens-Johnson syndrome after treatment with azithromycin: an uncommon culprit.
AB  - Azithromycin is a commonly prescribed antibiotic but is not considered a common
      etiologic agent for Stevens-Johnson syndrome (SJS). SJS is a dermatologic
      emergency that occurs within a spectrum of severity and can result in severe
      morbidity and mortality.

PMID- 26194399
TI  - Decreasing sepsis mortality at Kaiser Permanente Northern California.

PMID- 26194401
TI  - Survival without sequelae after prolonged cardiopulmonary resuscitation after
      electric shock.
AB  - "Electrical shock is the physiological reaction or injury caused by electric
      current passing through the human body. It occurs upon contact of a human body
      part with any source of electricity that causes a sufficient current through the
      skin, muscles, or hair causing undesirable effects ranging from simple burns to
      death." Ventricular fibrillation is believed to be the most common cause of death
      after electrical shock. "The ideal duration of cardiac resuscitation is unknown.
      Typically prolonged cardiopulmonary resuscitation is associated with poor
      neurologic outcomes and reduced long term survival. No consensus statement has
      been made and traditionally efforts are usually terminated after 15-30 minutes."
      The case under discussion seems worthy of the somewhat detailed description
      given. It is for a young man who survived after 65 minutes after electrical shock
      (ES) after prolonged high-quality cardiopulmonary resuscitation (CPR), multiple
      defibrillations, and artificial ventilation without any sequelae. Early start of
      adequate chest compressions and close adherence to advanced cardiac life support
      protocols played a vital role in successful CPR.

PMID- 26194402
TI  - Risk of persistent steroid dependency after switching from cyclosporine to
      mycophenolate mofetil in children with idiopathic nephrotic syndrome.

PMID- 26194403
TI  - The role of mast cells in functional GI disorders.
AB  - Functional gastrointestinal disorders (FGIDs) are characterized by chronic
      complaints arising from disorganized brain-gut interactions leading to
      dysmotility and hypersensitivity. The two most prevalent FGIDs, affecting up to
      16-26% of worldwide population, are functional dyspepsia and irritable bowel
      syndrome. Their etiopathogenic mechanisms remain unclear, however, recent
      observations reveal low-grade mucosal inflammation and immune activation, in
      association with impaired epithelial barrier function and aberrant neuronal
      sensitivity. These findings come to challenge the traditional view of FGIDs as
      pure functional disorders, and relate the origin to a tangible organic substrate.
      The mucosal inflammatory infiltrate is dominated by mast cells, eosinophils and
      intraepithelial lymphocytes in the intestine of FGIDs. It is well established
      that mast cell activation can generate epithelial and neuro-muscular dysfunction
      and promote visceral hypersensitivity and altered motility patterns in FGIDs,
      postoperative ileus, food allergy and inflammatory bowel disease. This review
      will discuss the role of mucosal mast cells in the gastrointestinal tract with a
      specific focus on recent advances in disease mechanisms and clinical management
      in irritable bowel syndrome and functional dyspepsia. 

PMID- 26194404
TI  - Surgical feasibility and biocompatibility of wide-field dual-array suprachoroidal
      transretinal stimulation prosthesis in middle-sized animals.
AB  - PURPOSE: To investigate the safety and efficacy of a newly-developed wide-field
      dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in middle
      sized animals. METHODS: The prosthesis consisted of two arrays with 50 to 74
      electrodes. To test the feasibility of implanting the prosthesis and its
      efficacy, the prosthesis was implanted for 14 days into two rabbits. Optical
      coherence tomography (OCT) and ophthalmoscopy were performed 7 and 14 days after
      the implantation. Then the rabbits were euthanized, eyes were enucleated, and the
      posterior segment of the eye was examined histologically. In a second experiment,
      the arrays were implanted into two cats, and their ability to elicit neural
      responses was determined by electrically evoked potentials (EEPs) at the chiasm
      and by optical imaging of the retina. RESULTS: All arrays were successfully
      implanted, and no major complications occurred during the surgery or during the 2
      week postoperative period. Neither OCT nor ophthalmoscopy showed any major
      complications or instability of the arrays. Histological evaluations showed only
      mild cellular infiltration and overall good retinal preservation. Stimulation of
      the retina by the arrays evoked EEPs recorded from the chiasm. Retinal imaging
      showed that the electrical pulses from the arrays altered the retinal images
      indicating an activation of retinal neurons. The thresholds were as low as 100
      MUA for a chiasm response and 300 MUA for the retinal imaging. CONCLUSION:
      Implantation of a newly-developed dual-array STS prosthesis for 2 weeks in
      rabbits was feasible surgically, and safe. The results of retinal imaging showed
      that the dual-array system was able to activate retinal neurons. We conclude that
      the dual-array design can be implanted without complication and is able to
      activate retinal neurons and optic nerve axons.

PMID- 26194405
TI  - Experts contradict established classification.

PMID- 26194406
TI  - Distribution and ecotoxicology of bioavailable metals and As in surface sediments
      of Paraguacu estuary, Todos os Santos Bay, Brazil.
AB  - Surface sediments collected in the intertidal zone of Paraguacu estuary in July,
      2013, were analyzed for organic matter, nitrogen, phosphorus, grain size
      fractions and partial concentrations of 16 metals. The USEPA 3051A method and ICP
      OES and CV-AAS techniques were chosen to metal analysis. Pollution indices (EF,
      Igeo and PIN) and a comparison with sediment quality guidelines (UET, ERL, ERM,
      TEL and PEL of NOAA) were conducted in order to evaluate the potential metal
      impacts over the area. Principal Component Analysis (PCA) and Pearson correlation
      results showed the importance of organic matter content and the fine-grained
      fraction of sediments on the control of the bioavailable metals distribution. The
      Paraguacu estuary already has anthropogenic enrichment relative to the background
      level, especially for Mn, whose values exceeded almost 30 times the background at
      one site (Mn: 1197.30 mg kg(-1)). However, metal levels are still below the
      reference values with the exception of Hg at one site (Hg: 0.25 mg kg(-1),
      exceeded TEL and ERL).

PMID- 26194407
TI  - n-Alkanes and stable C, N isotopic compositions as identifiers of organic matter
      sources in Posidonia oceanica meadows of Alexandroupolis Gulf, NE Greece.
AB  - We analyzed n-alkane contents and their stable carbon isotope composition, as
      well as the carbon and nitrogen isotope composition (delta(13)C, delta(15)N) of
      sediment organic matter and different tissues of Posidonia oceanica seagrass
      sampled in Alexandroupolis Gulf (A.G.), north-eastern Greece, during 2007-2011. n
      Alkane contents in P. oceanica and in sediments showed similar temporal trends,
      but relative to bulk organic carbon content, n-alkanes were much more enriched in
      sediments compared to seagrass tissue. Individual n-alkanes in sediments had
      similar values than seagrass roots and rhizomes and were more depleted in (13)C
      compared to seagrass leaves and sheaths, with delta(13)C values ranging from 
      350/00 to -280/00 and from -250/00 to -200/00, respectively. n-Alkane indexes
      such as the Carbon Preference Index, carbon number maximum, and n-alkane proxy 1
      (C23+C25/C23+C25+C29+C31) indicate strong inputs of terrestrial organic matter,
      while the presence of unresolved complex mixtures suggests potential oil
      pollution in some sampled areas.

PMID- 26194408
TI  - Dynamic modeling of environmental risk associated with drilling discharges to
      marine sediments.
AB  - Drilling discharges are complex mixtures of base-fluids, chemicals and
      particulates, and may, after discharge to the marine environment, result in
      adverse effects on benthic communities. A numerical model was developed to
      estimate the fate of drilling discharges in the marine environment, and
      associated environmental risks. Environmental risk from deposited drilling waste
      in marine sediments is generally caused by four types of stressors: oxygen
      depletion, toxicity, burial and change of grain size. In order to properly model
      these stressors, natural burial, biodegradation and bioturbation processes were
      also included. Diagenetic equations provide the basis for quantifying
      environmental risk. These equations are solved numerically by an implicit-central
      differencing scheme. The sediment model described here is, together with a fate
      and risk model focusing on the water column, implemented in the DREAM and OSCAR
      models, both available within the Marine Environmental Modeling Workbench (MEMW)
      at SINTEF in Trondheim, Norway.

PMID- 26194409
TI  - Patients' refusal of recommended treatment.
AB  - When patients require information to decide whether to accept recommended
      treatments, a question in both law and ethics is whether the same information is
      adequate whether they consent or refuse, or whether refusal requires more or
      repeated information. Refusals of recommended treatment can carry increased risks
      for patients' well-being and so require more emphatic disclosure without imposing
      pressure. A related question is whether guardians of dependents who would decline
      recommended treatment for themselves--for instance on religious grounds--can
      similarly decline it for their dependents. When pregnant women, children, and
      adolescents are able to give consent for recommended treatment, the question
      arises whether they are equally competent to refuse it and prevent their
      decisions being overridden by guardians or courts. Consenting to and refusing
      medical treatments recommended in one's own or dependents' best interests might
      not be the same sorts of decisions and could require different levels of
      disclosure and capacity.

PMID- 26194410
TI  - Identification of Candidates for Active Surveillance: Should We Change the
      Current Paradigm?
AB  - Active surveillance (AS) has been claimed to avoid overtreatment of prostate
      cancer (PCa). It remains unclear which patients may benefit from AS. One way to
      clarify this is to improve the definition of insignificant PCa. PSA and Gleason
      score--the basic instruments used to select patients for AS--suffer from
      systematic errors. The nomograms used to define insignificant PCa are based on
      patients whose disease was classified before changes were introduced in the 2005
      Consensus Conference on Gleason Grading; thus, the experience obtained cannot be
      directly applied to today's patients. Additionally, despite the standardization
      of prostate-specific antigen assays promoted by the World Health Organization,
      differences persist and could lead to misclassification of patients. These
      factors lead to an incorrect classification of patients into risk groups.
      Although new variables would increase risk group classification, the necessary
      first step is to optimize the use of both prostate-specific antigen serum levels
      and Gleason score.

PMID- 26194411
TI  - Gender differences in couple attachment behaviors as predictors of dietary habits
      and physical activity levels.
AB  - This study used an Actor-Partner Interdependence Model to examine the
      relationship between attachment behaviors and health practices, as measured by
      physical activity levels and dietary habits. The sample included 1031 married
      couples, the majority of which is Caucasian (83.8%). Results suggest that women's
      attachment behaviors significantly influenced their own health practices (p =
      .038), such that for every unit increase in poor attachment behaviors, women were
      199.8 percent more likely to have poor diet and low physical activity levels
      (exp(1.098) = 2.998). Men's attachment behaviors were not significantly related
      to their own health practices. There were also no significant partner paths.
      Implications for treating women who present with health problems are discussed,
      as are directions for future research.

PMID- 26194412
TI  - Beyond survivorship? A discursive analysis of how people with pancreatic cancer
      negotiate identity transitions in their health.
AB  - We explored how people negotiate, and respond to, identity transitions following
      a diagnosis of pancreatic cancer. Interviews with 19 people with pancreatic
      cancer were analysed using thematic discourse analysis. While discursively
      negotiating two transitions, 'moving from healthy to ill' and 'moving from active
      treatment to end-of-life care', participants positioned themselves as 'in
      control', 'optimistic' and managing their health and illness. In the absence of
      other discourses or models of life post-cancer, many people draw on the promise
      of survival. Moving away from 'survivorship' may assist people with advanced
      cancer to make sense of their lives in a short timeframe.

PMID- 26194413
TI  - Not eating like a pig: European wild boar wash their food.
AB  - Carrying food to water and either dunking or manipulating it before consumption
      has been observed in various taxa including birds, racoons and primates. Some
      animals seem to be simply moistening their food. However, true washing aims to
      remove unpleasant surface substrates such as grit and sand and requires a
      distinction between items that do and do not need cleaning as well as deliberate
      transportation of food to a water source. We provide the first evidence for food
      washing in suids, based on an incidental observation with follow-up experiments
      on European wild boar (Sus scrofa) kept at Basel Zoo, Switzerland. Here, all
      adult pigs and some juveniles of a newly formed group carried apple halves soiled
      with sand to the edge of a creek running through their enclosure where they put
      the fruits in the water and pushed them to and fro with their snouts before
      eating. Clean apple halves were never washed. This indicates that pigs can
      discriminate between soiled and unsoiled foods and that they are able to delay
      gratification for long enough to transport and wash the items. However, we were
      unable to ascertain to which degree individual and/or social learning brought
      this behaviour about. 

PMID- 26194414
TI  - Baboons (Papio papio), but not humans, break cognitive set in a visuomotor task.
AB  - Cognitive set can be both helpful and harmful in problem solving. A large set of
      similar problems may be solved mechanically by applying a single-solution method.
      However, efficiency might be sacrificed if a better solution exists and is
      overlooked. Despite half a century of research on cognitive set, there have been
      no attempts to investigate whether it occurs in nonhuman species. The current
      study utilized a nonverbal, computer task to compare cognitive set between 104
      humans and 15 baboons (Papio papio). A substantial difference was found between
      humans' and baboons' abilities to break cognitive set. Consistent with previous
      studies, the majority of humans were highly impaired by set, yet baboons were
      almost completely unaffected. Analysis of the human data revealed that children
      (aged 7-10) were significantly better able to break set than adolescents (11-18)
      and adults (19-68). Both the evolutionary and developmental implications of these
      findings are discussed. 

PMID- 26194415
TI  - Double-bellied latissimus dorsi free flap to correct full dental smile palsy.
AB  - A 45-year-old woman with left facial palsy presented to our department. She
      developed the condition after radical resection of a neurinoma of the homolateral
      VIII cranial nerve 2 years prior. On physical examination, a complete palsy of
      the lower third of the face was reported. Electromyographic examination showed no
      fibrillation potentials in mimic muscles. A latissimus dorsi muscle free flap (6
      cm * 3 cm), split into two bellies linked by their own neurovascular pedicle, was
      used to restore full-mouth smile. Ten years after surgery, the patient showed a
      near-natural smile without need of any ancillary procedure.

PMID- 26194416
TI  - Delayed diagnosis of spindle cell sarcoma presenting as a large mass on the back.

PMID- 26194417
TI  - Longitudinally extensive transverse myelitis and meningitis due to a rare
      infectious cause.

PMID- 26194418
TI  - Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell
      differentiation from M2 to M1 type, which mediates inhibition of tumour immune
      evasion via the Toll-like receptor 2 pathway.
AB  - Gr-1(+) CD11b(+) myeloid-derived suppressor cells (MDSCs) accumulate in tumor
      bearing animals and play a critical negative role during tumor immunotherapy.
      Strategies for inhibition of MDSCs are expected to improve cancer immunotherapy.
      Polysaccharide Agaricus blazei Murill (pAbM) has been found to have anti-cancer
      activity, but the underlying mechanism of this is poorly understood. Here, pAbM
      directly activated the purified MDSCs through inducing the expression of
      interleukin-6 (IL-6), IL-12, tumour necrosis factor and inducible nitric oxide
      synthase (iNOS), CD86, MHC II, and pSTAT1 of it, and only affected natural killer
      and T cells in the presence of Gr-1(+) CD11b(+) monocytic MDSCs. On further
      analysis, we demonstrated that pAbM could selectively block the Toll-like
      receptor 2 (TLR2) signal of Gr-1(+) CD11b(+) MDSCs and increased their M1-type
      macrophage characteristics, such as producing IL-12, lowering expression of
      Arginase 1 and increasing expression of iNOS. Extensive study showed that Gr-1(+)
      CD11b(+) MDSCs by pAbM treatment had less ability to convert the CD4(+) CD25(-)
      cells into CD4(+) CD25(+) phenotype. Moreover, result from selective depletion of
      specific cell populations in xenograft mice model suggested that the anti-tumour
      effect of pAbM was dependent on Gr-1(+ ) CD11b(+) monocytes, nether CD8(+) T
      cells nor CD4(+) T cells. In addition to, pAbM did not inhibit tumour growth in
      TLR2(-/-) mice. All together, these results suggested that pAbM, a natural
      product commonly used for cancer treatment, was a specific TLR2 agonist and had
      potent anti-tumour effects through the opposite of the suppressive function of Gr
      1(+) CD11b(+) MDSCs.

PMID- 26194420
TI  - Ambient PM2.5 exposure exacerbates severity of allergic asthma in previously
      sensitized mice.
AB  - OBJECTIVE: Epidemiological studies have shown that elevated concentrations of
      ambient particulate matter (aerodynamic diameter <=2.5 MUm; PM2.5) correlates
      with increased incidence of asthma. The aim of this study was to determine
      whether PM2.5 participates in the exacerbation of asthma. METHODS: Effects of 1,
      10 and 100 MUg PM2.5 instilled intratracheally in ovalbumin (OVA)-sensitized or
      asthmatic mice were compared. RESULTS: PM2.5 exposure in the OVA-sensitized and
      especially asthmatic groups increased Mch responsiveness in a dose-dependent
      manner. In OVA-sensitized groups, exposure to 1 MUg of PM2.5 caused no detectable
      lung inflammation, while 10 and 100 MUg of PM2.5 resulted in a slightly increased
      trend in numbers of neutrophils and macrophages. Compared with the asthmatic
      control group, both 10 and 100 MUg of PM2.5 provoked a significant increase in
      eosnophils and neutrophils whereas only 100 MUg of PM2.5 noticeably enhanced
      lymphocytes. In asthmatic groups, administration of 100 MUg of PM2.5 greatly
      increased levels of the pro-inflammatory cytokine TNF-alpha and Th2-related
      cytokines IL-4 and IL-10 in bronchoalveolar lavage fluid, but it decreased Th1
      related INF-gamma. In addition, 10 and 100 MUg of PM2.5 exacerbated inflammatory
      infiltration, goblet cell metaplasia and lung ultrastructure lesions in asthmatic
      mice. CONCLUSIONS: Our results suggested that acute exposure of PM2.5 could
      synergize with allergens in the subsequent challenge to aggravate the severity of
      asthma in sensitized mice, possibly by promoting a Th2-biased immune response.

PMID- 26194419
TI  - The Neuro-Environmental Loop of Plasticity: A Cross-Species Analysis of Parental
      Effects on Emotion Circuitry Development Following Typical and Adverse
      Caregiving.
AB  - Early experiences critically shape the structure and function of the brain.
      Perturbations in typical/species-expected early experiences are known to have
      profound neural effects, especially in regions important for emotional
      responding. Parental care is one species-expected stimulus that plays a
      fundamental role in the development of emotion neurocircuitry. Emerging evidence
      across species suggests that phasic variation in parental presence during the
      sensitive period of childhood affects the recruitment of emotional networks on a
      moment-to-moment basis. In addition, it appears that increasing independence from
      caregivers cues the termination of the sensitive period for environmental input
      into emotion network development. In this review, we examine how early parental
      care, the central nervous system, and behavior come together to form a 'neuro
      environmental loop,' contributing to the formation of stable emotion regulation
      circuits. To achieve this end, we focus on the interaction of parental care and
      the developing amygdala-medial prefrontal cortex (mPFC) network-that is at the
      core of human emotional functioning. Using this model, we discuss how individual
      or group variations in parental independence, across chronic and brief
      timescales, might contribute to neural and emotional phenotypes that have
      implications for long-term mental health. 

PMID- 26194421
TI  - Characterization of fecal vancomycin-resistant enterococci with acquired and
      intrinsic resistance mechanisms in wild animals, Spain.
AB  - The objectives were to evaluate the presence of vancomycin-resistant enterococci
      with acquired (VRE-a) and intrinsic (VRE-i) resistance mechanisms in fecal
      samples from different wild animals, and analyze their phenotypes and genotypes
      of antimicrobial resistance. A total of 348 cloacal/rectal samples from red
      legged partridges (127), white storks (81), red kites (59), and wild boars (81)
      (June 2014/February 2015) were inoculated in Slanetz-Bartley agar supplemented
      with vancomycin (4 MUg/mL). We investigated the susceptibility to 12
      antimicrobials and the presence of 19 antimicrobial resistance and five virulence
      genes. In addition, we performed multilocus sequence typing, detection of IS16
      and studied Tn1546 structure. One VRE-a isolate was identified in one wild boar.
      This isolate was identified as Enterococcus faecium, harbored vanA gene included
      into Tn1546 (truncated with IS1542/IS1216), and belonged to the new ST993. This
      isolate contained the erm(A), erm(B), tet(M), dfrG, and dfrK genes. Neither
      element IS16 nor the studied virulence genes were detected. Ninety-six VRE-i
      isolates were identified (89 Enterococcus gallinarum and seven Enterococcus
      casseliflavus), with the following prevalence: red kites (71.2 %), white storks
      (46.9 %), red-legged partridges (7.9 %), and wild boars (4.9 %). Most E.
      gallinarum isolates showed resistance to tetracycline (66.3 %) and/or
      erythromycin (46.1 %). High-level resistance to aminoglycosides was present among
      our VRE-i isolates: kanamycin (22.9 %), streptomycin (11.5 %), and gentamicin
      (9.4 %). In general, VRE-i isolates of red kites showed higher rates of
      resistance for non-glycopeptide agents than those of other animal species. The
      dissemination of acquired resistance mechanisms in natural environments could
      have implications in the global spread of resistance with public health
      implications.

PMID- 26194422
TI  - Risk factors and clinical aspects of delirium in elderly hospitalized patients in
      Iran.
AB  - BACKGROUND: Recognition of the risk factors of delirium has been clearly
      advantageous in preventing and managing it as it occurs. AIMS: The main aims of
      this study were to investigate the occurrence of delirium and identify the
      associated risk factors in a sample of hospitalized elderly in Southwestern Iran.
      METHODS: A cross-sectional, hospital-based study was performed on a total of 200
      elderly patients, admitted to a general hospital for various health reasons. Data
      were gathered over a 3-month period of time in 2010. Abbreviated Mental Test
      score (AMTs) used for delirium detection in post-admission days 1, 3, and 5,
      followed by clinical diagnostic confirmation according to the DSM-IV-TR criteria
      for delirium. Information regarding physical, cognitive, emotional, and
      functional states of the participants was collected, too. RESULTS: Delirium
      developed in 22 % of the participants. The demographic characteristics of the
      patients with delirium indicated that they were typically single, older men who
      lived alone and had a lower level of education and poorer functional status.
      Among other variables, the following were significantly associated with delirium:
      hemoglobin <=12 (P < 0.001); Blood urea nitrogen/creatinine ratio >=1/20 (P <
      0.005); and positive C-reactive protein (P = 0.022); depressive symptoms (P <
      0.001), and previous cognitive decline (P < 0.001). Patients with more than six
      different categories of medications were at high risk for delirium as well.
      CONCLUSIONS: Delirium is a serious and common problem in people over 60 years of
      age who are admitted to hospitals. Understanding risk factors and clinical
      aspects of delirium in elderly hospitalized patients will provide us with a
      better delirium management strategy.

PMID- 26194423
TI  - The CAM test: a novel tool to quantify the decline in vertical upper limb
      pointing movements with ageing.
AB  - BACKGROUND AND AIM: Although upper limb movements in the vertical plane are very
      commonly used during the activities of daily life, there is still a lack of a
      reliable and easy standardized procedure to quantify them. In particular, ageing
      is associated with a decline in performances of coordinated movements, but a tool
      to quantify this decline is missing. METHODS: We created a novel portable test
      called counting arm movement test (CAM test). Participants were asked to perform
      fast and accurate successive pointing movements towards two fixed targets
      (mechanical counters) located in a vertical plane in the parasagittal axis during
      three different time periods (15, 30, 45 s). Each upper limb was assessed
      separately. The test was evaluated in a group of 63 healthy subjects (mean age +/
      SD 49.1 +/- 19.8 years; F/M 33/30; range 18-87 years). RESULTS: Motor
      performances (number of clicks) significantly decreased as a function of age for
      both the dominant side (age effect; linear regression; p < 0.0001 for 15, 30 and
      45 s) and the non-dominant side (linear regression; p < 0.0001 for 15, 30 and 45
      s). Performances on the dominant and non-dominant side were linearly correlated
      with the time periods (p < 0.0001 on both sides). The symmetry index (ratio of
      performance on the dominant side divided by performance on the non-dominant side)
      was correlated linearly and positively with the duration of the test (y = 0.002x
      + 1.053; p = 0.0056). We also found a linear relationship between upper limb
      length and motor performance on the non-dominant side for 15 s (p = 0.023) and 45
      s (p = 0.041). The test was characterized by a very high correlation between the
      results obtained by two investigators during two successive sessions in a
      subgroup of 7 subjects (Pearson product moment correlation: 0.989 for the
      dominant side and 0.988 for the non-dominant side). CONCLUSION: The CAM test
      appears as a robust and low cost tool to quantify upper limb pointing movements.
      In particular, the test strongly discriminates the effects of age upon motor
      performances in upper limbs. Future studies are now required to establish the
      sensitivity, specificity and reliability of this procedure in selected
      neuromuscular or skeletal diseases affecting the elderly.

PMID- 26194424
TI  - Development and Integration of Antibody-Drug Conjugate in Non-Hodgkin Lymphoma.
AB  - Rituximab, a monoclonal antibody (MAb) against CD20, was the first MAb approved
      by the US Food and Drug Administration (FDA) for treatment of B cell non-Hodgkin
      lymphoma (B-NHL). Conjugating toxins to MAb was a technical challenge; however,
      with improvements in linker technology, immunoconjugates were constructed and
      revolutionized cancer treatment. Gemtuzumab ozogamicin was the first antibody
      drug conjugate (ADC) approved by the FDA. Because of the success of brentuximab
      vedotin and ado-trastuzumab emtansine in treating Hodgkin lymphoma (HL) and HER2
      positive breast cancer, respectively, newer ADCs are being investigated.
      Brentuximab vedotin is approved for both HL and anaplastic large cell lymphoma.
      Newer ADCs, such as polatuzumab vedotin (targeting CD79b), pinatuzumab vedotin
      (targeting CD22), inotuzumab ozogamicin (targeting CD19), SAR3419 (targeting
      CD19), IMGN529 (targeting CD37), and SGN-CD19A (targeting CD19), have shown
      promising preclinical and early clinical activity. These findings will change the
      landscape of B-NHL treatment away from age-old "CHOP"-based chemotherapies. 

PMID- 26194425
TI  - Erratum to: Promoting Female Condom Use Among Female University Students in
      KwaZulu-Natal, South Africa: Results of a Randomized Behavioral Trial.

PMID- 26194426
TI  - Antiretroviral Treatment and Sexual Risk Behavior in South Africa.
AB  - The sexual behavior of individuals living with HIV determines the onward
      transmission of HIV. With the understanding that antiretroviral therapy (ART)
      prevents transmission of HIV, the sexual behaviors of the individuals not on ART
      with unsuppressed viral loads becomes of the greatest importance in elucidating
      transmission. We assessed the association between being on ART and sexual risk
      behavior among those living with HIV in a nationally representative population
      based cross-sectional survey of households in South Africa that was conducted in
      2012. Of 2237 adults (aged 15-49) who tested HIV-seropositive, 667 (29.8 %) had
      detectable antiretroviral drugs in their blood specimens. Among males, 77.7 % of
      those on ART reported having had sex in the past year contrasted with 88.4 % of
      those not on ART (p = 0.001); among females, 72.2 % of those on ART reported
      having had sex in the past year while 80.3 % of those not on ART did (p < 0.001).
      For males and females, the odds of reporting consistent condom use and condom use
      at last sex were statistically significantly higher for individuals on ART
      compared to those not on ART (males: consistent condom use aOR 2.8, 95 % CI 1.6
      4.9, condom use at last sex aOR 2.6, 95 % CI 1.5-4.6; females: consistent condom
      use aOR 2.3, 95 % CI 1.7-3.1, condom use at last sex aOR 2.3, 95 % CI 1.7-3.1),
      while there were no statistically significant differences in odds of reporting
      multiple sexual partners in the past year. In this nationally representative
      population-based survey of South African adults, we found evidence of less risky
      sexual risk behavior among people living with HIV on ART compared to those not on
      ART.

PMID- 26194427
TI  - Large-Volume Microfluidic Cell Sorting for Biomedical Applications.
AB  - Microfluidic cell-separation technologies have been studied for almost two
      decades, but the limited throughput has restricted their impact and range of
      application. Recent advances in microfluidics enable high-throughput cell sorting
      and separation, and this has led to various novel diagnostic and therapeutic
      applications that previously had been impossible to implement using microfluidics
      technologies. In this review, we focus on recent progress made in engineering
      large-volume microfluidic cell-sorting methods and the new applications enabled
      by them. 

PMID- 26194428
TI  - High-Throughput Assessment of Cellular Mechanical Properties.
AB  - Traditionally, cell analysis has focused on using molecular biomarkers for basic
      research, cell preparation, and clinical diagnostics; however, new
      microtechnologies are enabling evaluation of the mechanical properties of cells
      at throughputs that make them amenable to widespread use. We review the current
      understanding of how the mechanical characteristics of cells relate to underlying
      molecular and architectural changes, describe how these changes evolve with cell
      state and disease processes, and propose promising biomedical applications that
      will be facilitated by the increased throughput of mechanical testing: from
      diagnosing cancer and monitoring immune states to preparing cells for
      regenerative medicine. We provide background about techniques that laid the
      groundwork for the quantitative understanding of cell mechanics and discuss
      current efforts to develop robust techniques for rapid analysis that aim to
      implement mechanophenotyping as a routine tool in biomedicine. Looking forward,
      we describe additional milestones that will facilitate broad adoption, as well as
      new directions not only in mechanically assessing cells but also in perturbing
      them to passively engineer cell state. 

PMID- 26194429
TI  - Anthelmintic activity of Artemisia vestita Wall ex DC. and Artemisia maritima L.
      against Haemonchus contortus from sheep.
AB  - Current study was designed to evaluate in vivo and in vitro anthelmintic activity
      of Artemisia vestita Wall ex DC. and Artemisia maritima L. against Haemonchus
      contortus in comparison with ivermectin to investigate the effect of plant
      extracts on survival of infective L3 and adults under in vitro condition. Plant
      extracts were given to H. contortus infected sheep orally and it was infected
      with L3 stage of H. contortus at dose of 5000 larvae/sheep. Total of 25-30 larvae
      were incubated with plant extracts in PBS alone and ivermectin at different
      concentration used as positive control. It was recorded that there is a
      significant decrease in fecal egg count (FEC) after post-treatment period for
      both plants. The highest fecal egg count reduction for A. vestita was 87.2% at
      100mg/kg while for A. maritima it was 84.5% on day 28 post-treatment.
      Investigated extracts indicated significant activity against larvae and adult
      worms. 

PMID- 26194430
TI  - In vitro infection by Leishmania infantum in the peripheral blood mononuclear
      cell-derived macrophages from crab-eating foxes (Cerdocyon thous).
AB  - Wild canids are natural reservoirs of visceral leishmaniais (VL). In Brazil, only
      the crab-eating fox (Cerdocyon thous) is a natural reservoir of this zoonotic
      disease, but there is still a lack of understanding regarding the sylvatic
      transmission of the Leishmania infantum infection. This is the first study on the
      isolation, cultivation and infection with L. infantum in the peripheral blood
      mononuclear cell-derived macrophages from crab-eating foxes. It is also the first
      to compare macrophages from crab-eating foxes to other canine macrophages under
      the same conditions. Blood samples collected from crab-eating foxes held at the
      local zoo were processed to obtain macrophages that were subsequently infected
      with stationary phase L. infantum promastigotes. The percentage of infected
      macrophages and intracellular amastigotes per 100 macrophages were similar in
      both fox and dog blood samples at 2h after infection. Unlike dog macrophages, in
      fox macrophages there was a significant reduction in the number of infected
      macrophages after 24 and 48 h. At 72 h after infection, the intracellular
      amastigotes were practically undetectable. These results indicate that crab
      eating foxes have cellular mechanisms of infection control as efficient as the
      domestic dog. Further study is required to discern the potential epidemiologic
      role of crab-eating foxes in the visceral leishmaniasis transmission cycle.

PMID- 26194432
TI  - Development of a Knowledge-based Application Utilizing Ontologies for the
      Continuing Site-specific JJ1017 Master Maintenance.
AB  - The purpose of this study was to develop the JJ1017 Knowledge-based Application
      (JKA) to support the continuing maintenance of a site-specific JJ1017 master
      defined by the JJ1017 guideline as a standard radiologic procedure master for
      medical information systems that are being adopted by some medical facilities in
      Japan. The method consisted of the following three steps: (1) construction of the
      JJ1017 Ontology (JJOnt) as a knowledge base using the Hozo (an environment for
      building/using ontologies); (2) development of modules (operation, I/O, graph
      modules) that are required to continue the maintenance of a site-specific JJ1017
      master; and (3) unit testing of the JKA that consists of the JJOnt and the
      modules. As a result, the number of classes included in the JJOnt was 21,697.
      Within the radiologic procedure classes included in the above, the ratio of a
      JJ1017 master code for an external beam radiotherapy was the highest (51%). In
      unit testing of the JKA, we checked the main operations (e.g., keyword search of
      a JJ1017 master code/code meaning, editing the description of classes, etc.). The
      JJOnt is a knowledge base for implementing features that medical technologists
      find necessary in medical information systems. To enable medical technologists to
      exchange/retrieve semantically accurate information while using medical
      information systems in the future, we expect the JKA to support the maintenance
      and improvement of the site-specific JJ1017 master.

PMID- 26194431
TI  - Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced
      nephropathy in rats.
AB  - Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no
      ideal treatment. Evidence suggest that multidrug therapy has more effect than
      monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the
      major active component of Salviae Miltiorrhizae Bunge. Previous studies have
      demonstrated that SAA is a multi-target agent and has various pharmacological
      activities. The pleiotropic properties of SAA predict its potential in the
      treatment of NS. The study investigated the effect of SAA on doxorubicin-induced
      nephropathy. The kidney function related-biochemical changes, hemorheological
      parameters and oxidative stress status were determined, and histological
      examination using light and transmission electron microcopies and western blot
      analysis were also performed. Results revealed that treatment with SAA alleviated
      histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia,
      reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA
      restored podocin expression, down-regulated the expression of NF-kappaB p65 and p
      IkappaBalpha while up-regulating IkappaBalpha protein expression. Overall, as a
      multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced
      nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury,
      improvement of hemorheology and hypolipidemic properties may constituent an
      important part of its therapeutic effects. All these indicate that SAA is likely
      to be a promising agent for NS. 

PMID- 26194433
TI  - Evaluation of Imaging Quality and ADC for the Tetrahedral Gradients of Diffusion
      Weighted Imaging.
AB  - The diffusion weighted images (DWIs) are used widely in clinical practice.
      Recently, the gradient overplus imaging was developed in addition to orthogonal
      technique for the duration method of motion-probing gradient pulses. The gradient
      overplus technique can reduce the load of a gradient strength, and enables
      setting of the shortest TE compared with the orthogonal gradients, and moreover
      it has the information on diffusion tensor. The apparent diffusion coefficient
      (ADC) values, signal-to-noise ratio (SNR), and geometric distortion were compared
      for the two duration methods of DWI using four different phantoms of coefficient
      of viscosity. In the gradient overplus, the time of smallest TE became smaller
      than the orthogonal gradients according to the increase of the b value. As a
      result, SNR increased by shortening of TE, and thus the geometric distortion was
      improved. Moreover, the ADC value did not show any difference in the two duration
      methods of DWI. The gradient overplus technique is a more useful technique in a
      clinical study than the orthogonal gradients because the quality of image is
      improved, and the ADC value is the same as the orthogonal gradients.

PMID- 26194434
TI  - Effects of Non-radioactive Material around Radioactive Material on PET Image
      Quality.
AB  - PURPOSE: Subcutaneous fat is a non-radioactive material surrounding the
      radioactive material. We developed a phantom, and examined the effect of
      subcutaneous fat on PET image quality. METHODS: We created a cylindrical
      nonradioactive mimic of subcutaneous fat, placed it around a cylindrical phantom
      in up to three layers with each layer having a thickness of 20 mm to reproduce
      the obesity caused by subcutaneous fat. In the cylindrical phantom, hot spheres
      and cold spheres were arranged. The radioactivity concentration ratio between the
      hot spheres and B.G. was 4:1. The radioactivity concentration of B.G. was changed
      as follows: 1.33, 2.65, 4.00, and 5.30 kBq/mL. 3D-PET images were collected
      during 10 minutes. RESULTS: When the thickness of the mimicked subcutaneous fat
      increased from 0 mm to 60 mm, noise equivalent count decreased by 58.9-60.9% at
      each radioactivity concentration. On the other hand, the percentage of background
      variability increased 2.2-5.2 times. Mimic subcutaneous fat did not decrease the
      percentage contrast of the hot spheres, and did not affect the cold spheres.
      CONCLUSION: Subcutaneous fat decreases the noise equivalent count and increases
      the percentage of background variability, which degrades PET image quality.

PMID- 26194435
TI  - New Regression Equation for 123I-IMP Non-invasive Cerebral Blood Flow Measurement
      Using the Graph Plot Method.
AB  - PURPOSE: A graph plot (GP) method using 123I-N-isopropyl-p-iodoamphetamine (123I
      IMP) has been proposed as a simple and non-invasive estimation of quantitative
      cerebral bloodflow (CBF). A regression equation for the GP method was estimated
      by the data of resting state. Therefore, the accuracy of CBF values in high flow
      range may be an underestimated possibility in this method.The aim of this study
      was to formulate a new regression equation for the GP method by the data of
      resting state and acetazolamide (ACZ) challenge, and to clarify the accuracy of
      it. METHODS: The images of 26 consecutive patients who underwent both 123I-IMP
      chest radioisotope-angiography (RIA) and single photon emission computed
      tomography (SPECT) examinations were used to construct the new regression
      equation. Examinations of the resting state and ACZ challenge were performed in
      different days. All patients were analyzed by both the GP method and
      autoradiography (ARG) method which is the conventional examination with the one
      point arterial blood sampling. A linear regression equation between the index of
      the input function was obtained by the GP method and CBF value of ARG. The linear
      regression equation based on the resting data was compared with the equation
      based on the resting and ACZ challenge (rest+stress) data. RESULTS: Goodliner
      correlation was obtained between the index of the input function obtained by the
      GP method and CBF value of the ARG method in the rest+stress state (y=2.75x+15.1,
      r=0.78). In contrast, correlation results between the index of the input function
      obtained by the GP method and CBF value of the ARG method in the resting state
      was expressed as y=2.28x+18.4, r=0.54 rCBF values based on the resting data was
      20% underestimated in the high flow range compared with values based on the
      rest+stress data. CONCLUSION: The new linear regression equation for the GP
      method is useful for clinical study. Key words: non-invasive cerebral blood flow
      measurement method, graph plot (GP), autoradiography (ARG), 123I-N-isopropyl-p
      iodoamphetamine (123I-IMP).

PMID- 26194436
TI  - 11. Application of Monte Carlo Simulation to Radiological Technology--No.2 Focus
      on Changed Particles.

PMID- 26194437
TI  - 8. Radiation Therapy for Brain Tumor--No.1 Focus on Liniac, Gamma Knife and
      CyberKnife Treatment.

PMID- 26194438
TI  - Research guidance given to me by Professor Kunio for writing an article in
      English.

PMID- 26194439
TI  - Activity of JIRA Industry Strategy Planning Office.

PMID- 26194440
TI  - Evolution in Japanese Society of Radiological Technology.

PMID- 26194441
TI  - What we have learned from a decade of ED crowding research.

PMID- 26194442
TI  - Distinct glucose-lowering properties in good responders treated with sitagliptin
      and alogliptin.
AB  - BACKGROUND AND OBJECTIVES: All dipeptidyl peptidase 4 (DPP-4) inhibitors display
      similar glycemic efficacies, although they differ greatly in their chemical
      structures and pharmacological properties. This may be due to the inclusions of
      non- or poor-responders in the analysis, thereby masking the real effects of
      these drugs. The aim of this study was to identify any differences in diabetic
      parameters only in good responders treated with sitagliptin and alogliptin.
      METHODS: Treatment naive subjects with type 2 diabetes mellitus were assigned to
      either sitagliptin 25-50 mg/day (n = 69) or alogliptin 12.5-25 mg/day monotherapy
      (n = 62) for 3 months. Only those who showed good response selected by a novel
      parameter called A1c index were further analysed (n = 24 for sitagliptin and n =
      21 for alogliptin). RESULTS: At baseline, FBG and BMI were significantly higher
      and CPR-index was significantly lower in alogliptin good responders. At 3 months,
      while similar reductions of HbA1c were observed in these two groups, decreases of
      fasting blood glucose (FBG) were significantly higher in alogliptin good
      responders. Homeostasis model assessment (HOMA)-R significantly decreased only in
      alogliptin good responders, while HOMA-B similarly and significantly increased in
      these two groups. BMI significantly increased only in sitagliptin good
      responders. Significant negative correlations were observed between A1c index and
      changes (Delta) of HOMA-B in both groups. By contrast, significant positive and
      negative correlations were observed between DeltaFBG and DeltaHOMA-R, and between
      DeltaFBG and DeltaHOMA-B, respectively, only in alogliptin good responders.
      CONCLUSIONS: These results implicate that the effects on diabetic parameters and
      the glucose-lowering mechanisms of these two drugs might be different in those
      who have good response with these drugs. Accordingly, the choice of these drugs
      may be dependent on the characteristics of the patients.

PMID- 26194443
TI  - Mental toughness as a moderator of the intention-behaviour gap in the
      rehabilitation of knee pain.
AB  - OBJECTIVES: The purpose of this study was to investigate the role of mental
      toughness in maximising the effect of intentions to perform rehabilitative
      exercises on behaviour among a sample of people with knee pain. DESIGN: Cross
      sectional survey, with a 2-week time-lagged assessment of exercise behaviour.
      METHODS: In total, 193 individuals (nfemale=107, nmale=84) aged between 18 and 69
      years (M=30.79, SD=9.39) participated, with 136 (70.5%) retained at both
      assessment points. At time 1, participants completed an online, multisection
      survey that encompassed measures of demographic details, severity of problems
      associated with the knee (e.g., pain, symptoms), past behaviour, mental
      toughness, and the theory of planned behaviour constructs (TPB; attitudes,
      subjective norms, perceived behavioural, intentions). Two weeks later,
      participants retrospectively reported their exercise behaviour for the past 14
      days using an online survey. RESULTS: Moderated regression analyses indicated
      that mental toughness and its interaction with intention accounted for an
      additional 3% and 4% of the variance in exercise behaviour, respectively. Past
      behaviour, attitudes, and mental toughness all had direct effects on behaviour,
      alongside a meaningful interaction between intentions and mental toughness.
      Specifically, intentions had a stronger effect on exercise behaviour among those
      individuals high in mental toughness compared to those low in this personal
      resource. CONCLUSIONS: The results of this study shed new light on the intention
      behaviour gap by indicating that mental toughness increases the likelihood that
      intention is translated into action.

PMID- 26194444
TI  - Breastfeeding and child development outcomes: an investigation of the nurturing
      hypothesis.
AB  - This study investigated whether the nurturing hypothesis - that breastfeeding
      serves as a proxy for family socio-economic characteristics and parenting
      behaviours - accounts for the association of breastfeeding with children's
      academic abilities. Data used were from the Child Development Supplement of the
      Panel Study of Income Dynamics, which followed up a cohort of 3563 children aged
      0-12 in 1997. Structural equation modelling simultaneously regressed outcome
      variables, including three test scores of academic ability and two subscales of
      behaviour problems, on the presence and duration of breastfeeding, family socio
      economic characteristics, parenting behaviours and covariates. Breastfeeding was
      strongly related to all three tests scores but had no relationships with
      behaviour problems. The adjusted mean differences in the Letter-Word
      Identification, Passage Comprehension) and Applied Problems test scores between
      breastfed and non-breastfed children were 5.14 [95% confidence interval (CI):
      3.14, 7.14], 3.46 (95% CI: 1.67, 5.26) and 4.24 (95% CI: 2.43, 6.04),
      respectively. Both socio-economic characteristics and parenting behaviours were
      related to higher academic test scores and were associated with a lower
      prevalence of externalising and internalising behaviour problems. The
      associations of breastfeeding with behaviour problems are divergent from those of
      socio-economic characteristics and parenting behaviours. The divergence suggests
      that breastfeeding may not be a proxy of socio-economic characteristics and
      parenting behaviours, as proposed by the nurturing hypothesis. The mechanism of
      breastfeeding benefits is likely to be different from those by which family socio
      economic background and parenting practices exert their effects. Greater clarity
      in understanding the mechanisms behind breastfeeding benefits will facilitate the
      development of policies and programs that maximise breastfeeding's impact.

PMID- 26194445
TI  - [Isocitrate dehydrogenase type I mutation as a prognostic factor in glioblastoma
      and a literature review].
AB  - OBJECTIVE: Treatment response and prognosis in glioblastoma (GBM) tumours can
      differ among patients, highlighting the growing relevance of genetic biomarkers
      to differentiate glioblastoma sub-types. The biomarker isocitrate dehydrogenase
      (IDH1) is currently receiving considerable attention. The objective of this work
      was to analyse the clinical and prognostic differences between glioblastomas with
      and without the IDH1 mutation. METHODS: A retrospective study was performed on
      patients with GBM who underwent surgery between 2007 and 2012. The inclusion
      criteria were: patient age between 18-85 years who underwent surgery for the
      first time with complete macroscopic resection, complete adjuvant treatment with
      chemotherapy and radiotherapy, and a Karnofsky performance score>70. RESULTS: A
      total of 61 patients (36 males/25 famales) were included and with a mean age of
      62.3 years. An IDH1mutation was found in 14 patients (23%). Median survival in
      patients with the IDH1 mutation (IDH1-m) was 23.6 months compared with 11.9
      months in those with the wild type IDH1 (IDH1-wt) (P=.028). Disease onset in IDH1
      m patients tended to be at a younger age, 58.7 vs. 63.4 years, but this
      difference was not statistically significant. CONCLUSION: Glioblastomas with IDH1
      m should be considered a different entity from the IDH1-wt, as their natural
      history and prognosis differ. In the near future we should be classified
      glioblastomas based on the presence of the IDH1 mutation.

PMID- 26194446
TI  - Targeted individual prophylaxis offers superior risk stratification for
      cytomegalovirus reactivation after liver transplantation.
AB  - Cytomegalovirus (CMV) can reactivate following liver transplantation. Management
      of patients currently considered low risk based on pretransplant serology remains
      contentious, with universal prophylaxis and preemptive strategies suffering from
      significant deficiencies. We hypothesized that a CMV-specific T cell assay
      performed early after transplant as part of a preemptive strategy could better
      stratify "low-risk" (recipient seropositive) patients. We conducted a
      prospective, blinded, observational study in 75 adult recipients. QuantiFERON
      cytomegalovirus was performed both before and at multiple times after transplant.
      Low-risk patients (n = 58) were monitored as per unit protocol and treatment was
      commenced if CMV > 1000 copies/mL (DNAemia). Twenty patients needed antiviral
      treatment for other reasons and were censored (mainly for rejection or herpes
      simplex virus infection); 19/38 (50%) of the remaining low-risk patients
      developed DNAemia at mean 34.6 days after transplant. A week 2 result of <0.1
      IU/mL was significantly associated with risk of subsequent DNAemia (hazard ratio
      [HR], 6.9; P = 0.002). The positive predictive value of 80% suggests these
      patients are inappropriately labeled low risk and are actually at high likelihood
      of CMV reactivation. A secondary cutoff of <0.2 IU/mL was associated with
      moderate risk (HR, 2.8; P = 0.01). In conclusion, a protocol based on a single
      early CMV-specific T cell based assay would offer improved risk stratification
      and individualization of patient management after transplant. This could offer
      improved drug and service utilization and potentially result in significant
      improvements over both currently used protocols to manage supposedly low-risk
      patients.

PMID- 26194448
TI  - Experimental model for controlling shear using the Ilizarov frame.
AB  - OBJECTIVE: This study has been designed to ascertain whether a standard
      configuration Ilizarov tibial frame can control shear motion at the fracture site
      of an oblique fracture within acceptable limits for axial micro-motion, and
      therefore promote bony union. If not, are there simple modifications to the frame
      design that can achieve this? METHODS: Four Ilizarov frame designs were tested on
      a load test rig. Fracture site shear displacement was measured using a clip gauge
      attached to an automated data recording system. FINDINGS: The standard Ilizarov
      frame allowed 4mm of fracture site displacement at 340N of load. Our fourth frame
      design, the locked olive frame, allowed a maximum of 0.61mm displacement at 700N.
      INTERPRETATION: This is one of only two studies to look at circular frame
      fracture site control in oblique fractures. This is the only study to
      characterise Ilizarov frame stiffness in oblique fractures. We have shown that
      the standard Ilizarov frame design is inadequate for control of oblique fractures
      in this mechanical model. Our data show that with the application of simple
      principles, the Ilizarov frame can be modified to provide better fracture site
      control. These frame designs can be applied clinically to reduce fracture site
      shear motion in oblique fractures, resulting in improved union rates.

PMID- 26194447
TI  - Pre-transplant comorbidity burden and post-transplant chronic graft-versus-host
      disease.
AB  - The Haematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) was designed
      as a predictor of non-relapse mortality after HCT. Chronic graft-versus-host
      disease (GVHD) contributes to mortality after HCT. Here, we investigated whether
      the HCT-CI could predict development of chronic GVHD or post-chronic GVHD
      mortality. We retrospectively analysed data from 2909 patients treated with
      allogeneic HCT for malignant and non-malignant haematological conditions at four
      institutions. In Cox regression models adjusted for potential confounders,
      increasing HCT-CI was not statistically significantly associated with the
      development of chronic GVHD [hazard ratio (HR) = 1.02, P = 0.34]. Yet, the index
      was associated with an increased risk of non-relapse mortality (HR = 1.29, P <
      0.0001) as well as overall mortality (HR = 1.25, P < 0.001) following the
      development of chronic GVHD. The association between HCT-CI and post-chronic GVHD
      mortality was similar regardless of donor type or stem cell source. HCT-CI scores
      could be incorporated in the design of clinical trials for treatment of chronic
      GVHD.

PMID- 26194449
TI  - Mediating effects of resistance training skill competency on health-related
      fitness and physical activity: the ATLAS cluster randomised controlled trial.
AB  - The purpose of this study was to examine the mediating effect of resistance
      training skill competency on percentage of body fat, muscular fitness and
      physical activity among a sample of adolescent boys participating in a school
      based obesity prevention intervention. Participants were 361 adolescent boys
      taking part in the Active Teen Leaders Avoiding Screen-time (ATLAS) cluster
      randomised controlled trial: a school-based program targeting the health
      behaviours of economically disadvantaged adolescent males considered "at-risk" of
      obesity. Body fat percentage (bioelectrical impedance), muscular fitness (hand
      grip dynamometry and push-ups), physical activity (accelerometry) and resistance
      training skill competency were assessed at baseline and post-intervention (i.e.,
      8 months). Three separate multi-level mediation models were analysed to
      investigate the potential mediating effects of resistance training skill
      competency on each of the study outcomes using a product-of-coefficients test.
      Analyses followed the intention-to-treat principle. The intervention had a
      significant impact on the resistance training skill competency of the boys, and
      improvements in skill competency significantly mediated the effect of the
      intervention on percentage of body fat and the combined muscular fitness score.
      No significant mediated effects were found for physical activity. Improving
      resistance training skill competency may be an effective strategy for achieving
      improvements in body composition and muscular fitness in adolescent boys. 

PMID- 26194450
TI  - Intracardiac echocardiography for percutaneous transluminal septal myocardial
      ablation in the treatment of hypertrophic obstructive cardiomyopathy.

PMID- 26194451
TI  - Input-output analysis on the economic impact of medical care in Japan.
AB  - OBJECTIVES: Since the Cabinet's decision concerning the Basic Policies 2005, the
      Japanese government has implemented specific measures to suppress increases in
      national medical care expenditure. However, we believe that the economic
      significance of medical care should be quantified in terms of its economic impact
      on national medical care expenditure. No one has examined the economic impact of
      all medical institutions in Japan using data from a statement of profits and
      losses. We used an input-output analysis to quantitatively estimate economic
      impact of medical care and examined its estimation range with a probabilistic
      sensitivity analysis. METHODS: To estimate the economic impact and economic
      impact multipliers of all medical institutions in Japan, an input-output analysis
      model was developed using an input-output table, statement of profits and losses,
      margin rates, employee income rates, consumption propensity and an equilibrium
      output model. Probabilistic sensitivity analysis was conducted using a Monte
      Carlo simulation. RESULTS: Economic impact of medical care in all medical
      institutions was Y72,107.4 billion ($661.5 billion). This impact yielded a 2.78
      fold return of medical care expenditure with a 95 % confidence interval ranging
      from 2.74 to 2.90. CONCLUSION: Economic impact of medical care in Japan was two
      to three times the medical care expenditure (per unit). Production inducement of
      medical care is comparable to other industrial sectors that are highly
      influential toward the economy. The contribution to medical care should be
      evaluated more explicitly in national medical care expenditure policies.

PMID- 26194452
TI  - Epidemiology, attitudes and perceptions toward cigarettes and hookah smoking
      amongst adults in Jordan.
AB  - OBJECTIVES: The aims of this study are to assess cigarette and hookah smoking
      rates amongst adult population in Jordan and to determine predictors of smoking
      status. Selected beliefs, perceptions and attitudes toward cigarettes and hookah
      smoking were also assessed. METHODS: This cross-sectional study was conducted in
      five regional governorates of Jordan through face-to-face interviews on a random
      sample of adult population aged 18-79 years. Data was collected using a piloted
      questionnaire based on the Global Adult Tobacco Questionnaire. RESULTS: The
      overall prevalence of cigarette smoking in our sample (869) was 59.1 % amongst
      males and 23.3 % amongst females, while the overall prevalence of hookah smoking
      was 18.9 % amongst males and 23.1 % amongst females. Leisure and imitation were
      the most commonly reported reasons for smoking. Regardless of smoking status,
      people were aware of health risks associated smoking and also had negative
      perceptions toward smoking. CONCLUSIONS: Smoking rates for both genders have
      reached alarmingly high rates in Jordan. There is an urgent need for a
      comprehensive national programme to target the country's growing burden of
      smoking. Suggestions on leisure time activities should be included in such
      programmes.

PMID- 26194453
TI  - Preventive Effects on Birth Outcomes: Buffering Impact of Maternal Stress,
      Depression, and Anxiety.
AB  - OBJECTIVE: Although maternal stress, anxiety, and depression have been linked to
      negative birth outcomes, few studies have investigated preventive interventions
      targeting maternal mental health as a means of reducing such problems. This
      randomized controlled study examines whether Family Foundations (FF)-a transition
      to parenthood program for couples focused on promoting coparenting quality, with
      previously documented impact on maternal stress, depression, and anxiety-can
      buffer the negative effects of maternal mental health problems. METHODS: To
      assess the effects of FF, we used a randomized block design with a sample of 259
      expectant mothers assigned to FF or a control condition and analyzed using
      propensity score models. We examine two-way interactions of condition
      (intervention vs. control) with maternal mental health problems (financial
      stress, depression, and anxiety) on birth outcomes (birth weight, days in
      hospital for mothers and infants). For birth weight, we assess whether
      intervention effects depend on length of gestation by including a third
      interaction term. RESULTS: FF buffered (p < 0.05) the negative impact of maternal
      mental health problems on birth weight and both mother and infant length of post
      partum hospital stay. For birth weight, assignment to FF was associated with
      higher birth weight for infants born before term. CONCLUSIONS: These results
      demonstrate that a psycho-educational program for couples focused on enhancing
      mutual coparental support, with preventive effects on maternal mental health, can
      reduce incidence of birth problems among women at elevated risk. Such
      improvements in birth outcomes could translate into substantial reductions in
      public and personal healthcare costs. Future work should assess mediating
      mechanisms of intervention impact and cost-benefit ratio of the intervention.
      CLINICAL TRIALS REGISTRATION: The Family Foundations follow-up intervention study
      is currently registered with www.clinicaltrials.gov . The study identifier is
      NCT01907412.

PMID- 26194454
TI  - Quantitative phosphoproteomic analysis reveals gamma-bisabolene inducing p53
      mediated apoptosis of human oral squamous cell carcinoma via HDAC2 inhibition and
      ERK1/2 activation.
AB  - gamma-Bisabolene, one of main components in cardamom, showed potent in vitro and
      in vivo anti-proliferative activities against human oral squamous cell carcinoma
      (OSCC). gamma-Bisabolene activated caspases-3/9 and decreased mitochondrial
      memebrane potential, leading to apoptosis of OSCC cell lines (Ca9-22 and SAS),
      but not normal oral fibroblast cells. Phosphoproteome profiling of OSCC cells
      treated with gamma-bisabolene was identified using TiO2-PDMS plate and LC-MS/MS,
      then confirmed using Western blotting and real-time RT-PCR assays.
      Phosphoproteome profiling revealed that gamma-bisabolene increased the
      phosphorylation of ERK1/2, protein phosphatases 1 (PP1), and p53, as well as
      decreased the phosphorylation of histone deacetylase 2 (HDAC2) in the process of
      apoptosis induction. Protein-protein interaction network analysis proposed the
      involvement of PP1-HDAC2-p53 and ERK1/2-p53 pathways in gamma-bisabolene-induced
      apoptosis. Subsequent assays indicated gamma-bisabolene eliciting p53 acetylation
      that enhanced the expression of p53-regulated apoptotic genes. PP1 inhibitor-2
      restored the status of HDAC2 phosphorylation, reducing p53 acetylation and PUMA
      mRNA expression in gamma-bisabolene-treated Ca9-22 and SAS cells. Meanwhile, MEK
      and ERK inhibitors significantly decreased gamma-bisabolene-induced PUMA
      expression in both cancer cell lines. Notably, the results ascertained the
      involvement of PP1-HDAC2-p53 and ERK1/2-p53 pathways in mitochondria-mediated
      apoptosis of gamma-bisabolene-treated cells. This study demonstrated gamma
      bisabolene displaying potent anti-proliferative and apoptosis-inducing activities
      against OSCC in vitro and in vivo, elucidating molecular mechanisms of gamma
      bisabolene-induced apoptosis. The novel insight could be useful for developing
      anti-cancer drugs.

PMID- 26194455
TI  - ESGAR consensus statement on liver MR imaging and clinical use of liver-specific
      contrast agents.
AB  - OBJECTIVES: To develop a consensus and provide updated recommendations on liver
      MR imaging and the clinical use of liver-specific contrast agents. METHODS: The
      European Society of Gastrointestinal and Abdominal Radiology (ESGAR) formed a
      multinational European panel of experts, selected on the basis of a literature
      review and their leadership in the field of liver MR imaging. A modified Delphi
      process was adopted to draft a list of statements. Descriptive and Cronbach's
      statistics were used to rate levels of agreement and internal reliability of the
      consensus. RESULTS: Three Delphi rounds were conducted and 76 statements composed
      on MR technique (n = 17), clinical application of liver-specific contrast agents
      in benign, focal liver lesions (n = 7), malignant liver lesions in non-cirrhotic
      (n = 9) and in cirrhotic patients (n = 18), diffuse and vascular liver diseases
      (n = 12), and bile ducts (n = 13). The overall mean score of agreement was 4.84
      (SD +/-0.17). Full consensus was reached in 22 % of all statements in all working
      groups, with no full consensus reached on diffuse and vascular diseases.
      CONCLUSIONS: The consensus provided updated recommendations on the methodology,
      and clinical indications, of MRI with liver specific contrast agents in the study
      of liver diseases. KEY POINTS: * Liver-specific contrast agents are recommended
      in MRI of the liver. * The hepatobiliary phase improves the detection and
      characterization of hepatocellular lesions. * Liver-specific contrast agents can
      improve the detection of HCC.

PMID- 26194458
TI  - Substrate effects on Li(+) electrodeposition in Li secondary batteries with a
      competitive kinetics model.
AB  - A Li22Sn5 alloy was prepared as a novel substrate of the metallic Li anode of
      rechargeable Li batteries for Li(+) deposition. The performance of this alloy
      substrate was compared with those of Li, Cu, and Sn substrates. The deposition
      stripping cycling performance of Li on the substrates was studied through the
      galvanostatic charge-discharge method and cyclic voltammetry. The morphologies of
      the substrates before and after Li(+) deposition were investigated through
      scanning electron microscopy and digital video microscopy. The electrochemical
      kinetics of Li(+) electrodeposition on the different substrates was studied
      through the galvanostatic pulse method and linear sweep voltammetry. The solid
      electrolyte interface films of Li deposits on the substrates were characterized
      through electrochemical impedance spectroscopy. Results show that Li22Sn5 is an
      excellent substrate for metallic Li electrodes. "The competitive kinetics model"
      was proposed as a novel mechanistic model to explain the electrodeposition
      behavior of Li(+) on general substrates based on electrochemical kinetic
      principles. 

PMID- 26194457
TI  - Panitumumab: A safe option for oncologic patients sensitized to galactose-alpha
      1,3-galactose.

PMID- 26194456
TI  - Prevalence of degenerative and spondyloarthritis-related magnetic resonance
      imaging findings in the spine and sacroiliac joints in patients with persistent
      low back pain.
AB  - OBJECTIVE: To estimate the prevalence of degenerative and spondyloarthritis (SpA)
      related magnetic resonance imaging (MRI) findings in the spine and sacroiliac
      joints (SIJs) and analyse their association with gender and age in persistent low
      back pain (LBP) patients. METHODS: Degenerative and SpA-related MRI findings in
      the whole spine and SIJs were evaluated in Spine Centre patients aged 18-40 years
      with LBP. RESULTS: Among the 1,037 patients, the prevalence of disc degeneration,
      disc contour changes and vertebral endplate signal (Modic) changes were 87 % (+/
      SEM 1.1), 82 % (+/-1.2) and 48 % (+/-1.6). All degenerative spinal findings were
      most frequent in men and patients aged 30-40 years. Spinal SpA-related MRI
      findings were rare. In the SIJs, 28 % (+/-1.4) had at least one MRI finding, with
      bone marrow oedema being the most common (21 % (+/-1.3)). SIJ erosions were most
      prevalent in patients aged 18-29 years and bone marrow oedema in patients aged 30
      40 years. SIJ sclerosis and fatty marrow deposition were most common in women.
      SIJ bone marrow oedema, sclerosis and erosions were most frequent in women
      indicating pregnancy-related LBP. CONCLUSION: The high prevalence of SIJ MRI
      findings associated with age, gender, and pregnancy-related LBP need further
      investigation of their clinical importance in LBP patients. KEY POINTS: * The
      location of vertebral endplate signal changes supports a mechanical aetiology. *
      Several sacroiliac joint findings were associated with female gender and
      pregnancy-related back pain. * Sacroiliac joint bone marrow oedema was frequent
      and age-associated, indicating a possible degenerative aetiology. * More
      knowledge of the clinical importance of sacroiliac joint MRI findings is needed.

PMID- 26194459
TI  - Unilateral calf swelling.

PMID- 26194460
TI  - Online combination algorithm for non-invasive assessment of chronic hepatitis B
      related liver fibrosis and cirrhosis in resource-limited settings.
AB  - OBJECTIVE: The use of commercially available noninvasive markers for chronic
      hepatitis B (CHB) related fibrosis is not widely available in developing
      countries so clinicians in those countries frequently use free alternatives. We
      aimed to create an optimized algorithm for selection of patients with the highest
      probability for presence/absence of significant liver fibrosis and cirrhosis
      based on the use of multiple free scores. METHODS: We evaluated six free
      noninvasive markers for CHB related fibrosis against liver biopsy and selected
      the best thresholds for prediction/exclusion of significant fibrosis and
      cirrhosis in CHB patients. Algorithm based on four scores and their corresponding
      thresholds was created. RESULTS: The calculator based on developed algorithm can
      be found at http://www.chb-lfc.com. We evaluated 211 patients in main group and
      65 patients in external validation group. We selected four scores for creation of
      combination algorithm. The algorithm was able to classify 123/211 (58.3%)
      patients with a 93.5% accuracy of correct classification for prediction of
      presence/absence of significant fibrosis in main group. In validation group, the
      algorithm was able to classify 48/65 (73.8%) of patients with 93.8% (45/48)
      overall accuracy. When used to predict presence/absence of cirrhosis, the
      algorithm was able to correctly classify 181/211 (85.8%) and 59/65 (90.8%) of
      patients in main and validation group, respectively, with an overall accuracy of
      97.8% and 98.3%, respectively. CONCLUSION: Developed algorithm based on routine
      laboratory tests is a usable, applicable and accurate tool for diagnosis of CHB
      related fibrosis and cirrhosis, suitable for resource-limited settings where more
      expensive modalities are unavailable.

PMID- 26194461
TI  - Nursing intervention to enhance outpatient chemotherapy symptom management:
      Patient-reported outcomes of a randomized controlled trial.
AB  - BACKGROUND: The authors conducted a randomized controlled trial to evaluate a
      nurse practitioner (NP)-delivered symptom management intervention for patients
      initiating chemotherapy for nonmetastatic cancer. The aim was to reduce patient
      reported symptom burden by facilitating patient-NP collaboration and the early
      management of symptoms. METHODS: At the time of the first chemotherapy visit,
      adult participants with nonmetastatic breast, colorectal, or lung cancer (120
      participants) completed self-report measures and were then randomly assigned to
      standard care plus the intervention or standard care alone. Intervention
      participants received proactive telephone calls from their oncology team NP
      during the week after each of the first 2 chemotherapy administration visits.
      Measures were repeated at the second and third chemotherapy visits. Group
      differences were analyzed with regard to patient-reported symptoms (Memorial
      Symptom Assessment Scale-Short Form items), satisfaction with care (Family
      Caregiver Satisfaction-patient scale), and the likelihood of depression or
      anxiety symptoms (Patient Health Questionnaire-4). RESULTS: At the time of the
      first visit, 50.8% of participants reported >=1 physical symptom, most commonly
      lack of energy (35.8%) and drowsiness (30.8%). The number of symptoms (gamma
      coefficient [gamma] = 0.16; P<.001), symptom distress (gamma = 0.45; P<.001), and
      satisfaction with care (gamma = 0.24; P = .004) increased whereas the likelihood
      of anxiety symptoms decreased (gamma = -0.19; P = .02) and the likelihood of
      depression symptoms did not change (gamma = 0.01; P = .91). Outcomes did not
      differ by randomized group. Randomized group interacted with emetogenic potential
      in predicting symptom distress (gamma = 0.43; P = .03) and satisfaction with care
      (gamma = -0.45; P = .045). CONCLUSIONS: The intervention did not appear to reduce
      symptom burden compared with standard care. Early symptoms highlight the
      importance of continuing to examine strategies to improve symptom management
      during chemotherapy for nonmetastatic disease.

PMID- 26194462
TI  - Surface-catalyzed C-C covalent coupling strategies toward the synthesis of low
      dimensional carbon-based nanostructures.
AB  - Carbon-based nanostructures have attracted tremendous interest because of their
      versatile and tunable properties, which depend on the bonding type of the
      constituting carbon atoms. Graphene, as the most prominent representative of the
      pi-conjugated carbon-based materials, consists entirely of sp(2)-hybridized
      carbon atoms and exhibits a zero band gap. Recently, countless efforts were made
      to open and tune the band gap of graphene for its applications in semiconductor
      devices. One promising method is periodic perforation, resulting in a graphene
      nanomesh (GNM), which opens the band gap while maintaining the exceptional
      transport properties. However, the typically employed lithographic approach for
      graphene perforation is difficult to control at the atomic level. The
      complementary bottom-up method using surface-assisted carbon-carbon (C-C)
      covalent coupling between organic molecules has opened up new possibilities for
      atomically precise fabrication of conjugated nanostructures like GNM and graphene
      nanoribbons (GNR), although with limited maturity. A general drawback of the
      bottom-up approach is that the desired structure usually does not represent the
      global thermodynamic minimum. It is therefore impossible to improve the long
      range order by postannealing, because once the C-C bond formation becomes
      reversible, graphene as the thermodynamically most stable structure will be
      formed. This means that only carefully chosen precursors and reaction conditions
      can lead to the desired (non-graphene) material. One of the most popular and
      frequently used organic reactions for on-surface C-C coupling is the Ullmann
      reaction of aromatic halides. While experimentally simple to perform, the
      irreversibility of the C-C bond formation makes it a challenge to obtain long
      range ordered nanostructures. With no postreaction structural improvement
      possible, the assembly process must be optimized to result in defect-free
      nanostructures during the initial reaction, requiring complete reaction of the
      precursors in the right positions. Incomplete connections typically result when
      mobile precursor monomers are blocked from reaching unsaturated reaction sites of
      the preformed nanostructures. For example, monomers may not be able to reach a
      randomly formed internal cavity of a two-dimensional (2D) nanostructure island
      due to steric hindrance in 2D confinement, leaving reaction sites in the internal
      cavity unsaturated. Wrong connections between precursor monomers, here defined as
      intermolecular C-C bonds forcing the monomer into a nonideal position within the
      structure, are usually irreversible and can induce further structural defects.
      The relative conformational flexibility of the monomer backbones permits
      connections between deformed monomers when they encounter strong steric
      hindrance. This, however, usually leads to heterogeneous structural motifs in the
      formed nanostructures. This Account reviews some of the latest developments
      regarding on-surface C-C coupling strategies toward the synthesis of carbon-based
      nanostructures by addressing the above-mentioned issues. The strategies include
      Ullmann coupling and other, "cleaner" alternative C-C coupling reactions like
      Glaser coupling, cyclo-dehydrogenation, and dehydrogenative coupling. The choice
      of substrate materials and precursor designs is crucial for optimizing substrate
      reactivity and precursor diffusion rates, and to reduce events of wrong linkage.
      Hierarchical polymerization is employed to steer the coupling route, which
      effectively improves the completeness of the reaction. Effects of byproducts on
      nanostructure formation is comprehended with both experimental and theoretical
      studies. 

PMID- 26194463
TI  - Playback responses of socially monogamous black-fronted titi monkeys to simulated
      solitary and paired intruders.
AB  - Many birds and primates use loud vocalizations to mediate agonistic interactions
      with conspecifics, either as solos by males or females, or as coordinated duets.
      The extensive variation in duet complexity, the contribution of each sex, and the
      context in which duets are produced suggest that duets may serve several
      functions, including territory and mate defense. Titi monkeys (Callicebus spp.)
      are believed to defend their home range via solo loud calls or coordinated duets.
      Yet there are remarkably few experimental studies assessing the function of these
      calls. Observations of interactions between wild established groups and solitary
      individuals are rare and, therefore, controlled experiments are required to
      simulate such situations and evaluate the mate and joint territorial defense
      hypotheses. We conducted playback experiments with three free-ranging groups of
      habituated black-fronted titi monkeys (Callicebus nigrifrons) to test these
      hypotheses. We found that titi monkeys responded to the three conspecific
      playback treatments (duets, female solos, and male solos) and did not respond to
      the heterospecific control treatment. The monkeys did not show sex-specific
      responses to solos (N = 12 trials). Partners started to duet together in 79% of
      their responses to playback-simulated rivals (N = 14 calls in response to
      playback). Males started to approach the loudspeaker before females regardless of
      the type of stimulus. The strength of the response of mated pairs to all three
      conspecific treatments was similar. Overall, our results are consistent with the
      idea that black-fronted titi monkeys use their loud calls in intergroup
      communication as a mechanism of joint territorial defense.

PMID- 26194465
TI  - Africa needs streamlined regulation to support the deployment of GM crops.
AB  - Future food security in sub-Saharan Africa (SSA) requires enhancement of its crop
      production. Transgenic crops with a poverty focus can enhance harvests and are
      available for staples such as cooking bananas and plantains. One constraint is
      optimisation of national biosafety processes to support rapid and safe uptake of
      such beneficial crops. 

PMID- 26194467
TI  - A computational method for the identification of new candidate carcinogenic and
      non-carcinogenic chemicals.
AB  - Cancer is one of the leading causes of human death. Based on current knowledge,
      one of the causes of cancer is exposure to toxic chemical compounds, including
      radioactive compounds, dioxin, and arsenic. The identification of new
      carcinogenic chemicals may warn us of potential danger and help to identify new
      ways to prevent cancer. In this study, a computational method was proposed to
      identify potential carcinogenic chemicals, as well as non-carcinogenic chemicals.
      According to the current validated carcinogenic and non-carcinogenic chemicals
      from the CPDB (Carcinogenic Potency Database), the candidate chemicals were
      searched in a weighted chemical network constructed according to chemical
      chemical interactions. Then, the obtained candidate chemicals were further
      selected by a randomization test and information on chemical interactions and
      structures. The analyses identified several candidate carcinogenic chemicals,
      while those candidates identified as non-carcinogenic were supported by a
      literature search. In addition, several candidate carcinogenic/non-carcinogenic
      chemicals exhibit structural dissimilarity with validated carcinogenic/non
      carcinogenic chemicals.

PMID- 26194468
TI  - Low bone mineral density and risk of incident fracture in HIV-infected adults.
AB  - BACKGROUND: Prevalence rates of low bone mineral density (BMD) and bone fractures
      are higher among HIV-infected adults compared with the general United States (US)
      population, but the relationship between BMD and incident fractures in HIV
      infected persons has not been well described. METHODS: Dual energy X-ray
      absorptiometry (DXA) results of the femoral neck of the hip and clinical data
      were obtained prospectively during 2004-2012 from participants in two HIV cohort
      studies. Low BMD was defined by a T-score in the interval >-2.5 to <-1.0
      (osteopenia) or <=-2.5 (osteoporosis). We analysed the association of low BMD
      with risk of subsequent incident fractures, adjusted for sociodemographics, other
      risk factors and covariables, using multivariable proportional hazards
      regression. RESULTS: Among 1,006 participants analysed (median age 43 years [IQR
      36-49], 83% male, 67% non-Hispanic white, median CD4(+) T-cell count 461
      cells/mm(3) [IQR 311-658]), 36% (n=358) had osteopenia and 4% (n=37)
      osteoporosis; 67 had a prior fracture documented. During 4,068 person-years of
      observation after DXA scanning, 85 incident fractures occurred, predominantly
      rib/sternum (n=18), hand (n=14), foot (n=13) and wrist (n=11). In multivariable
      analyses, osteoporosis (adjusted hazard ratio [aHR] 4.02, 95% CI 2.02, 8.01) and
      current/prior tobacco use (aHR 1.59, 95% CI 1.02, 2.50) were associated with
      incident fracture. CONCLUSIONS: In this large sample of HIV-infected adults in
      the US, low baseline BMD was significantly associated with elevated risk of
      incident fracture. There is potential value of DXA screening in this population.

PMID- 26194464
TI  - Phosphorylation status determines the opposing functions of Smad2/Smad3 as STAT3
      cofactors in TH17 differentiation.
AB  - Transforming growth factor-beta (TGF-beta) and interleukin-6 (IL-6) are the
      pivotal cytokines to induce IL-17-producing CD4(+) T helper cells (TH17); yet
      their signalling network remains largely unknown. Here we show that the highly
      homologous TGF-beta receptor-regulated Smads (R-Smads): Smad2 and Smad3
      oppositely modify STAT3-induced transcription of IL-17A and retinoic acid
      receptor-related orphan nuclear receptor, RORgammat encoded by Rorc, by acting as
      a co-activator and co-repressor of STAT3, respectively. Smad2 linker
      phosphorylated by extracellular signal-regulated kinase (ERK) at the serine 255
      residue interacts with STAT3 and p300 to transactivate, whereas carboxy-terminal
      unphosphorylated Smad3 interacts with STAT3 and protein inhibitor of activated
      STAT3 (PIAS3) to repress the Rorc and Il17a genes. Our work uncovers carboxy
      terminal phosphorylation-independent noncanonical R-Smad-STAT3 signalling network
      in TH17 differentiation. 

PMID- 26194469
TI  - Effectiveness of the extended parallel process model in promoting colorectal
      cancer screening.
AB  - OBJECTIVE: Relatives of colorectal cancer (CRC) patients are at increased risk
      for the disease, yet screening rates still remain low. Guided by the Extended
      Parallel Process Model, we examined the impact of a personalized, remote risk
      communication intervention on behavioral intention and colonoscopy uptake in
      relatives of CRC patients, assessing the original additive model and an
      alternative model in which each theoretical construct contributes uniquely.
      METHODS: We collected intention-to-screen and medical record-verified colonoscopy
      information on 218 individuals who received the personalized intervention.
      RESULTS: Structural equation modeling showed poor main model fit (root mean
      square error of approximation (RMSEA) = 0.109; standardized root mean residual
      (SRMR) = 0.134; comparative fit index (CFI) = 0.797; Akaike information criterion
      (AIC) = 11,601; Bayesian information criterion (BIC) = 11,884). However, the
      alternative model (RMSEA = 0.070; SRMR = 0.105; CFI = 0.918; AIC = 11,186; BIC =
      11,498) showed good fit. Cancer susceptibility (B = 0.319, p < 0.001) and
      colonoscopy self-efficacy (B = 0.364, p < 0.001) perceptions predicted intention
      to screen, which was significantly associated with colonoscopy uptake (B = 0.539,
      p < 0.001). CONCLUSIONS: Our findings provide support of the utility of Extended
      Parallel Process Model for designing effective interventions to motivate CRC
      screening in persons at increased risk when individual elements of the model are
      considered. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26194470
TI  - Comparative Study of Soybean Oil and the Mixed Fatty Acids as Acyl Donors for
      Enzymatic Preparation of Feruloylated Acylglycerols in Ionic Liquids.
AB  - Feruloylated acylglycerols (FAGs) are the lipophilic derivatives of ferulic acid.
      In this work, soybean oil (SBO) and the mixed fatty acids (MFA) were selected as
      fatty acyl donors, and reacted with glyceryl monoferulate (GMF) to prepare FAGs
      in ionic liquids (ILs). Effect of various reaction parameters (time, temperature,
      enzyme concentration, and substrate ratio) and ILs on the GMF conversion and the
      reaction selectivity for FAGs formation were investigated. Response surface
      methodology (RSM) based on a 3-level-4-factor Box-Behnken experimental design was
      employed to evaluate the inactive effect of reaction parameters. For the
      esterification of GMF with MFA, the maximum GMF conversion (98.9 +/- 0.9%) and
      FAG yield (88.9 +/- 0.6%) were achieved in [C10mim]PF6. However, for the
      transesterification of GMF with SBO, the maximum GMF conversion (94.3 +/- 0.7%)
      and FAG yield (83.8 +/- 1.0%) were obtained in [C12mim]PF6. High FAG
      selectivities (~0.90) were also obtained using SBO or MFA as acyl donors. 

PMID- 26194471
TI  - Relationship between circulating tumor cells and epithelial to mesenchymal
      transition in early breast cancer.
AB  - BACKGROUND: Circulating tumor cells (CTCs) play a crucial role in tumor
      dissemination and are an independent survival predictor in breast cancer (BC)
      patients. Epithelial to mesenchymal transition (EMT) is involved in cancer
      invasion and metastasis. The aim of this study was to assess correlation between
      CTCs and expression of EMT transcription factors TWIST1 and SLUG in breast tumor
      tissue. METHODS: This study included 102 early BC patients treated by primary
      surgery. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic
      cells using RossetteSepTM negative selection kit. RNA extracted from CD45
      depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, FOXC2
      and ZEB1) and epithelial (KRT19) gene transcripts by qRT-PCR. Expression of
      TWIST1 and SLUG in surgical specimens was evaluated by immunohistochemistry and
      quantified by multiplicative score. RESULTS: CTCs were detected in 24.5 %
      patients. CTCs exhibiting only epithelial markers were present in 8.8 % patients,
      whereas CTCs with only EMT markers were observed in 12.8 % of pts and CTCs co
      expressing both markers were detected in 2.9 % pts. We observed lack of
      correlation between CTCs and expression of TWIST1 and SLUG in breast cancer cells
      or cancer associated stroma. Lack of correlation was observed for epithelial CTCs
      as well as for CTCs with EMT. CONCLUSIONS: In this translational study, we showed
      a lack of association between CTCs and expression of EMT-inducing transcription
      factors, TWIST1 and SLUG, in breast tumor tissue. Despite the fact that EMT is
      involved in cancer invasion and metastasis our results suggest, that expression
      of EMT proteins in unselected tumor tissue is not surrogate marker of CTCs with
      either mesenchymal or epithelial features.

PMID- 26194472
TI  - Streptococcal IdeS: therapeutic potential for Guillain-Barre syndrome.
AB  - Plasma exchange and intravenous immunoglobulin are effective in treating Guillain
      Barre syndrome (GBS) probably because the former removes IgG autoantibodies and
      complement and the latter inhibits complement activation subsequent to the
      autoantibody binding to peripheral nerve antigens. IgG degrading enzyme of
      Streptococcus pyogenes (IdeS) can cleave the pathogenic autoantibodies into
      F(ab')2 and Fc. The purpose of this study is to show whether IdeS has novel
      therapeutic potential for GBS. Sera with anti-ganglioside IgG antibodies from 15
      patients with GBS or Miller Fisher syndrome were used. We tested whether IdeS
      cleaved the anti-ganglioside IgG antibodies and inhibited deposition of activated
      complement component on ELISA plates. IdeS efficiently cleaved IgG and blocked
      complement activation mediated by anti-GM1, anti-GD1a and anti-GQ1b IgG
      antibodies. IdeS has therapeutic potential for GBS and related conditions. 

PMID- 26194473
TI  - Insight into the esterase like activity demonstrated by an imidazole appended
      self-assembling hydrogelator.
AB  - A low molecular weight hydrogelator with a covalently appended imidazole moiety
      is reported. Capable of percolating water in the pH range of 6 to 8, it proves to
      be an efficient catalyst upon self-assembly, showing Michaelis-Menten type
      kinetics. Activities at different pH values correlated with dramatic structural
      changes were observed. It can hydrolyse p-nitrophenyl acetate (pNPA) as well as
      inactivated esters, and L and D-phenylalanine methyl esters. The enhanced
      activity can be related to the conglomeration of catalytic groups upon
      aggregation resulting in their close proximity and the formation of hydrophobic
      pockets.

PMID- 26194474
TI  - Correction: A supramolecular approach for designing emissive solid-state
      carbazole arrays.

PMID- 26194475
TI  - Successful use of cryocrit for monitoring response to therapeutic plasma exchange
      in type 1 cryoglobulinemia.
AB  - Waldenstrom macroglobulinemia (WM) is a clinical syndrome that is defined as
      lymphoplasmacytic lymphoma with bone marrow involvement and IgM monoclonal
      gammopathy of any level. In some instances WM can result in a type I
      cryoglobulinemia with very high cryocrits, which is unusual in type II and III
      cryoglobulinemia. We describe a case of an 80 year old male with WM, severe type
      I cryoglobulinemia, and an extremely elevated cryocrit (69%). Over the course of
      five weeks we performed nine therapeutic plasma exchanges (TPE), and after seven
      treatments his cryocrit had decreased to 6% with improvement in his symptoms. By
      monitoring his cryocrit throughout his TPE sessions, we were able to assess his
      response to treatment, determine the ideal length of treatment in addition to his
      symptomatic improvement. J. Clin. Apheresis 31:403-404, 2016. (c) 2015 Wiley
      Periodicals, Inc. 

PMID- 26194476
TI  - Couple based family planning education: changes in male involvement and
      contraceptive use among married couples in Jimma Zone, Ethiopia.
AB  - BACKGROUND: Family planning contributes substantially in achieving the Millennium
      Development Goals. Recently, male involvement has gained considerable attention
      in family planning programs but the implementation thereof remains a challenge.
      In that context, our study aimed at measuring the effect of a six-month-long
      family planning education program on male involvement in family planning, as well
      as on couples' contraceptive practice. METHODS: We conducted a quasi-experimental
      research among 811 married couples in Jimma Zone, southwest Ethiopia. Our study
      consisted of an intervention and a control group for comparative purpose; and
      surveyed before and after the implementation of the intervention. The
      intervention consisted of family planning education, given to both men and women
      at the household level in the intervention arm, in addition to monthly community
      gatherings. During the intervention period, households in the control group were
      not subject to particular activities but had access to routine health care
      services. RESULTS: We obtained follow-up data from 760 out of 786 (96.7%) couples
      who were originally enrolled in the survey. Findings were compared within and
      between groups before and after intervention surveys. At the baseline,
      contraceptive use in both control and intervention households were similar. After
      the intervention, we observed among men in the intervention arm a significantly
      higher level of willingness to be actively involved in family planning compared
      to the men in the control arm (p < 0.001). In addition, the difference between
      spouses that discussed family planning issues was less reported within the
      control group, both in the case of men and women ((p = 0.031) and (p < 0.001))
      respectively. In general, a significant, positive difference in male involvement
      was observed. Concerning contraceptive use, there was change observed among the
      intervention group who were not using contraception at baseline. CONCLUSIONS:
      This study showed that family planning educational intervention, which includes
      both spouses and promotes spousal communication, might be useful to foster
      contraceptive practice among couples. The results also offer practical
      information on the benefits of male involvement in family planning as a best
      means to increase contraceptive use. Thus, providing opportunities to reinforce
      family planning education may strengthen the existing family planning service
      delivery system.

PMID- 26194477
TI  - Half of the children who received oral immunotherapy for a cows' milk allergy
      consumed milk freely after 2.5 years.
AB  - AIM: Strict milk protein avoidance has been the standard therapy of cows' milk
      allergy (CMA) in children, but oral immunotherapy (OIT) seems to provide an
      alternative treatment. The aim of this study was to evaluate the impact of OIT on
      milk consumption during the first 2.5 years after a start of OIT. METHODS: This
      open-label, noncontrolled, real-life OIT study was conducted in 74 children with
      CMA, who were aged 5-15. It included a 6-month induction phase and a 2-year
      maintenance phase. Data on the complete 2.5-year trial were available for 57
      children. RESULTS: Most of the children (82%) completed the 6-month induction
      phase and were able to consume at least 200 mL of milk or 6400 mg of milk protein
      a day. After the 2-year maintenance phase, half were consuming milk daily. Risk
      factors for OIT failure during the induction phase were asthma and high milk
      specific immunoglobulin E, but a history of anaphylaxis before OIT was not.
      Allergies to eggs or wheat decreased the risk of immediate OIT failure.
      CONCLUSION: This study confirmed the efficacy of milk OIT in real life, including
      the whole spectrum of persistent CMA at school age, and revealed certain risk
      factors associated with OIT failure.

PMID- 26194478
TI  - Unusual microbial lactonization and hydroxylation of asiatic acid by Umbelopsis
      isabellina.
AB  - Asiatic acid (1) is a natural triterpenoid isolated from Centella asiatica. This
      paper reports the microbial transformation of asiatic acid by an endophytic
      fungus Umbelopsis isabellina to obtain derivatives potentially useful for further
      studies. Incubation of asiatic acid with U. isabellina afforded two derivatives
      2alpha,3beta,7beta, 23-tetrahydroxyurs-12-ene-28-oic acid (2) and
      2alpha,3beta,7beta,23-tetrahydroxyurs-11-ene-28,13-lactone (3). The structures of
      these compounds were elucidated by spectral data. Compound 3 has formed an
      unusual lactone. These two products are new compounds. The possible
      transformation passway was also discussed. 

PMID- 26194479
TI  - Allopatric integrations selectively change host transcriptomes, leading to varied
      expression efficiencies of exotic genes in Myxococcus xanthus.
AB  - BACKGROUND: Exotic genes, especially clustered multiple-genes for a complex
      pathway, are normally integrated into chromosome for heterologous expression. The
      influences of insertion sites on heterologous expression and allotropic
      expressions of exotic genes on host remain mostly unclear. RESULTS: We compared
      the integration and expression efficiencies of single and multiple exotic genes
      that were inserted into Myxococcus xanthus genome by transposition and attB-site
      directed recombination. While the site-directed integration had a rather stable
      chloramphenicol acetyl transferase (CAT) activity, the transposition produced
      varied CAT enzyme activities. We attempted to integrate the 56-kb gene cluster
      for the biosynthesis of antitumor polyketides epothilones into M. xanthus genome
      by site-direction but failed, which was determined to be due to the insertion
      size limitation at the attB site. The transposition technique produced many
      recombinants with varied production capabilities of epothilones, which, however,
      were not paralleled to the transcriptional characteristics of the local sites
      where the genes were integrated. Comparative transcriptomics analysis
      demonstrated that the allopatric integrations caused selective changes of host
      transcriptomes, leading to varied expressions of epothilone genes in different
      mutants. CONCLUSIONS: With the increase of insertion fragment size, transposition
      is a more practicable integration method for the expression of exotic genes.
      Allopatric integrations selectively change host transcriptomes, which lead to
      varied expression efficiencies of exotic genes.

PMID- 26194481
TI  - A nickel complex of a conjugated bis-dithiocarbazate Schiff base for the
      photocatalytic production of hydrogen.
AB  - We report a nickel complex containing a conjugated bis-dithiocarbazate ligand
      that is an active catalyst for the reduction of protons into hydrogen gas. Light
      driven hydrogen generation is observed from a system containing this molecular
      nickel catalyst coupled with a fluorescein photosensitizer and triethylamine
      sacrificial donor. The photocatalytic system is stable for over 70 hours,
      achieving 3300 turnovers with respect to catalyst. The complex is also an active
      electrocatalyst for proton reduction with catalysis occurring at -1.7 V vs.
      Fc(+)/Fc. The nickel bis-dithiocarbazate complex represents a highly active and
      stable catalyst for hydrogen generation. 

PMID- 26194480
TI  - B cells in the aging immune system: time to consider B-1 cells.
AB  - The investigation of immune senescence has uncovered many changes in B cell
      development, maintenance, and function with increasing age. However, most of
      these studies have focused on conventional B cell subsets in the spleen. The B-1
      cell subset is an essential arm of the innate immune system, which in general has
      been understudied in terms of immune senescence. Here, we review what is
      currently known about B cells during aging and go on to describe why B-1 cell
      biology is an important component of the aging immune system in the context of
      diseases that most affect the aged population. 

PMID- 26194482
TI  - The oral case presentation: toward a performance-based rhetorical model for
      teaching and learning.
AB  - The oral case presentation is an important communicative activity in the teaching
      and assessment of students. Despite its importance, not much attention has been
      paid to providing support for teachers to teach this difficult task to medical
      students who are novices to this form of communication. As a formalized piece of
      talk that takes a regularized form and used for a specific communicative goal,
      the case presentation is regarded as a rhetorical activity and awareness of its
      rhetorical and linguistic characteristics should be given due consideration in
      teaching. This paper reviews practitioners' and the limited research literature
      that relates to expectations of medical educators about what makes a good case
      presentation, and explains the rhetorical aspect of the activity. It is found
      there is currently a lack of a comprehensive model of the case presentation that
      projects the rhetorical and linguistic skills needed to produce and deliver a
      good presentation. Attempts to describe the structure of the case presentation
      have used predominantly opinion-based methodologies. In this paper, I argue for a
      performance-based model that would not only allow a description of the rhetorical
      structure of the oral case presentation, but also enable a systematic examination
      of the tacit genre knowledge that differentiates the expert from the novice. Such
      a model will be a useful resource for medical educators to provide more
      structured feedback and teaching support to medical students in learning this
      important genre. 

PMID- 26194485
TI  - Intraoperative CT as a registration benchmark for intervertebral motion
      compensation in image-guided open spinal surgery.
AB  - PURPOSE: An accurate and reliable benchmark of registration accuracy and
      intervertebral motion compensation is important for spinal image guidance. In
      this study, we evaluated the utility of intraoperative CT (iCT) in place of bone
      implanted screws as the ground-truth registration and illustrated its use to
      benchmark the performance of intraoperative stereovision (iSV). METHODS: A
      template-based, multi-body registration scheme was developed to individually
      segment and pair corresponding vertebrae between preoperative CT and iCT of the
      spine. Intervertebral motion was determined from the resulting vertebral pair
      wise registrations. The accuracy of the image-driven registration was evaluated
      using surface-to-surface distance error (SDE) based on segmented bony features
      and was independently verified using point-to-point target registration error
      (TRE) computed from bone-implanted mini-screws. Both SDE and TRE were used to
      assess the compensation accuracy using iSV. RESULTS: The iCT-based technique was
      evaluated on four explanted porcine spines (20 vertebral pairs) with artificially
      induced motion. We report a registration accuracy of 0.57 [Formula: see text]
      0.32 mm (range 0.34-1.14 mm) and 0.29 [Formula: see text] 0.15 mm (range 0.14
      0.78 mm) in SDE and TRE, respectively, for all vertebrae pooled, with an average
      intervertebral rotation of [Formula: see text] (range 1.5[Formula: see text]
      7.9[Formula: see text]). The iSV-based compensation accuracy for one sample (four
      vertebrae) was 1.32 [Formula: see text] 0.19 mm and 1.72 [Formula: see text] 0.55
      mm in SDE and TRE, respectively, exceeding the recommended accuracy of 2 mm.
      CONCLUSION: This study demonstrates the effectiveness of iCT in place of invasive
      fiducials as a registration ground truth. These findings are important for future
      development of on-demand spinal image guidance using radiation-free images such
      as stereovision and ultrasound on human subjects.

PMID- 26194486
TI  - Automatic measurement and visualization of focal femoral cartilage thickness in
      stress-based regions of interest using three-dimensional knee models.
AB  - PURPOSE: Thinning of cartilage is a common manifestation of osteoarthritis. This
      study addresses the need of measuring the focal femoral cartilage thickness at
      the weight- bearing regions of the knee by developing a reproducible and
      automatic method from MR images. METHODS: 3D models derived from semiautomatic MR
      image segmentations were used in this study. Two different methods were examined
      for identifying the mechanical loading of the knee articulation. The first was
      based on a generic weight-bearing regions definition, derived from gait
      characteristics and cadaver studies. The second used a physically based
      simulation to identify the patient-specific stress distribution of the femoral
      cartilage, taking into account the forces and movements of the knee. For this
      purpose, four different scenarios were defined in our 3D finite element (FE)
      simulations. The radial method was used to calculate the cartilage thickness in
      stress-based regions of interest, and a study was performed to validate the
      accuracy and suitability of the radial thickness measurements. RESULTS: Detailed
      focal maps using our simulation data and regional measurements of cartilage
      thickness are given. We present the outcome of the different simulation scenarios
      and discuss how the internal/external rotations of the knee alter the overall
      stress distribution and affect the shape and size of the calculated weight
      bearing areas. The use of FE simulations allows for a patient-specific
      calculation of the focal cartilage thickness. CONCLUSION: It is important to
      assess the quantification of focal knee cartilage morphology to monitor the
      progression of joint diseases or related treatments. When this assessment is
      based on MR images, accurate and robust tools are required. In this paper, we
      presented a set of techniques and methodologies in order to accomplish this goal
      and move toward personalized medicine.

PMID- 26194487
TI  - Surgical process analysis identifies lack of connectivity between sequential
      fluoroscopic 2D alignment as a critical impediment in femoral intramedullary
      nailing.
AB  - PURPOSE: Identifying key steps and barriers within complex and simple surgical
      procedures can be accomplished in a structured and rigorous manner using surgical
      process modeling. For lower extremity long bone fracture stabilization, the
      current standard of care is closed intramedullary (IM) nailing, which, despite
      its widespread use, is associated with challenges that greatly impact operative
      time and lead to the frustration of medical staff. The aim of this study was to
      identify challenging surgical steps in IM nailing and understand their underlying
      causation. METHODS: Eight semi-structured interviews with staff orthopedic
      surgeons and eight detailed surgical observations were conducted to understand
      the surgical steps, challenges and adapted techniques used in IM nailing.
      Hierarchical decomposition was then utilized to structure the IM nailing surgical
      procedure into phases, steps and activities. RESULTS: In the developed IM nailing
      surgical process model, the most challenging steps were identified as fracture
      reduction (75%) and entry point selection (25%), both of which were associated
      with high levels of frustration in the observed surgeries. Both of these steps
      utilize 2D fluoroscopic imaging to guide 3D alignment. Challenges arise when the
      alignment in one plane is lost while adjusting the alignment in the perpendicular
      plane. This leads to unpredictable repetition of activities which can be time
      consuming and frustrating. CONCLUSION: Identifying the causation of surgical
      challenges in IM nailing through surgical process modeling forms a knowledge base
      that can be used to guide future improvements to techniques and surgical
      instrumentation.

PMID- 26194489
TI  - Hyperglycemia in acute coronary syndromes: from mechanisms to prognostic
      implications.
AB  - Hyperglycemia is a frequent condition in patients with acute coronary syndromes
      (ACS). Hyperglycemia during ACS is caused by an inflammatory and adrenergic
      response to ischemic stress, when catecholamines are released and glycogenolysis
      induced. Although the involved pathophysiological mechanisms have not yet been
      fully elucidated, it is believed that hyperglycemia is associated with an
      increase in free fat acids (which induce cardiac arrhythmias), insulin
      resistance, chemical inactivation of nitric oxide and the production of oxygen
      reactive species (with consequent microvascular and endothelial dysfunction), a
      prothrombotic state, and vascular inflammation. It is also related to myocardial
      metabolic disorders, leading to thrombosis, extension of the damaged area,
      reduced collateral circulation, and ischemic preconditioning. In the last few
      years, several observational studies demonstrated that hyperglycemia in ACS is a
      powerful predictor of survival, increasing the risk of immediate and long-term
      complications in patients both with and without previously known diabetes
      mellitus. Glucose management strategies in ACS may improve outcomes in patients
      with hyperglycemia, perhaps by reducing inflammatory and clotting mediators, by
      improving endothelial function and fibrinolysis and by reducing infarct size.
      Recent clinical trials of insulin in ACS have resulted in varying levels of
      benefit, but the clinical benefit of an aggressive treatment with insulin is yet
      unproved. 

PMID- 26194490
TI  - Assessment of the quality of fall detection and management in primary care in the
      Netherlands based on the ACOVE quality indicators.
AB  - We determined adherence to nine fall-related ACOVE quality indicators to
      investigate the quality of management of falls in the elderly population by
      general practitioners in the Netherlands. Our findings demonstrate overall low
      adherence to these indicators, possibly indicating insufficiency in the quality
      of fall management. Most indicators showed a positive association between
      increased risk for functional decline and adherence, four of which with
      statistical significance. INTRODUCTION: This study aims to investigate the
      quality of detection and management of falls in the elderly population by general
      practitioners in the Netherlands, using the Assessing Care of Vulnerable Elders
      (ACOVE) quality indicators. METHODS: Community-dwelling persons aged 70 years or
      above, registered in participating general practices, were asked to fill in a
      questionnaire designed to determine general practitioner (GP) adherence to fall
      related indicators. We used logistic regression to estimate the association
      between increased risk for functional decline-quantified by the Identification of
      Seniors At Risk for Primary Care score-and adherence. We then cross-validated the
      self-reported falls with medical records. RESULTS: Of the 950 elders responding
      to our questionnaire, only 10.6 % reported that their GP proactively asked them
      about falls. Of the 160 patients who reported two or more falls, or one fall for
      which they visited the GP, only 23.1 % had fall documentation in their records.
      Adherence ranged between 13.6 and 48.6 %. There was a significant positive
      association between the ISAR-PC scores and adherence in four QIs. Documentation
      of falls was highest (36.7 %) in patients whom the GP had proactively asked about
      falls. CONCLUSION: Based on patient self-reports, adherence to the ACOVE fall
      related indicators was poor, suggesting that the quality of evaluation and
      management of falls in community-dwelling older persons in the Netherlands is
      poor. The documentation of falls and fall-related risk factors was also poor.
      However, for most QIs, adherence to them increased with the increase in the risk
      of functional decline.

PMID- 26194492
TI  - Medication persistence in older women with osteoporosis: a pilot study.
AB  - Most osteoporosis patients stop their medications before they should. Side
      effects are the most common reason patients in this sample stopped their
      medication before they told their physician. Physicians should use shared
      decision-making and discuss side effects of osteoporosis medications with their
      patients and explain the risks of the medications. INTRODUCTION: The aims of this
      study were to (a) qualitatively examine reasons for medication non-persistence in
      osteoporosis, and (b) investigate how medication non-persistence in osteoporosis
      is associated with outcome expectations, self-efficacy, trust in physicians, and
      health locus of control. METHODS: Subjects were recruited from online support
      groups to answer an anonymous online survey. Subjects were eligible if they (a)
      were female, (b) were at least 40 years of age, (c) self-identify as having
      osteoporosis, and (d) have taken at least one medication for osteoporosis. During
      the survey, subjects completed measures of self-efficacy, outcome expectations,
      trust in physicians generally, health locus of control, and demographic
      information. RESULTS: Thirty-four subjects completed the online survey and had
      usable data. Approximately 82 % (n = 28) of subjects reported discontinuing an
      osteoporosis medication without first consulting a physician. The most common
      reason patients discontinued an osteoporosis medication was adverse effects.
      Subjects were more likely to discontinue their medications when they had poorer
      outcome expectations on average (p = 0.01), had lower trust in physicians on
      average (p < 0.0001), and had more of a doctors-centered locus of control (p =
      0.03). Self-efficacy, age, insurance, status, and other measures of locus of
      control were not associated with medication non-persistence. CONCLUSIONS: Side
      effects are a significant concern for women with osteoporosis and may be a cause
      for medication non-persistence.

PMID- 26194491
TI  - Age-associated declines in muscle mass, strength, power, and physical
      performance: impact on fear of falling and quality of life.
AB  - This 3-year longitudinal study among older adults showed that declining muscle
      mass, strength, power, and physical performance are independent contributing
      factors to increased fear of falling, while declines of muscle mass and physical
      performance contribute to deterioration of quality of life. Our findings
      reinforce the importance of preserving muscle health with advancing age.
      INTRODUCTION: The age-associated loss of skeletal muscle quantity and function
      are critical determinants of independent physical functioning in later life.
      Longitudinal studies investigating how decrements in muscle components of
      sarcopenia impact fear of falling (FoF) and quality of life (QoL) in older adults
      are lacking. METHODS: Twenty-six healthy older subjects (age, 74.1 +/- 3.7; Short
      Physical Performance Battery (SPPB) score >=10) and 22 mobility-limited older
      subjects (age, 77.2 +/- 4.4; SPPB score <=9) underwent evaluations of lower
      extremity muscle size and composition by computed tomography, strength and power,
      and physical performance at baseline and after 3-year follow-up. The Falls
      Efficacy Scale (FES) and Short Form-36 questionnaire (SF-36) were also
      administered at both timepoints to assess FoF and QoL, respectively. RESULTS: At
      3-year follow-up, muscle cross-sectional area (CSA) (p < 0.013) and power
      decreased (p < 0.001), while intermuscular fat infiltration increased (p <
      0.001). These decrements were accompanied with a longer time to complete 400 m by
      22 +/- 46 s (p < 0.002). Using linear mixed-effects regression models, declines
      of muscle CSA, strength and power, and SPPB score were associated with increased
      FES score (p < 0.05 for each model). Reduced physical component summary score of
      SF-36 over follow-up was independently associated with decreased SPPB score (p <
      0.020), muscle CSA (p < 0.046), and increased 400 m walk time (p < 0.003).
      CONCLUSIONS: In older adults with and without mobility limitations, declining
      muscle mass, strength, power, and physical performance contribute independently
      to increase FoF, while declines of muscle mass and physical performance
      contribute to deterioration of QoL. These findings provide further rationale for
      developing interventions to improve aging muscle health.

PMID- 26194493
TI  - A common polymorphism rs1800247 in osteocalcin gene was associated with serum
      osteocalcin levels, bone mineral density, and fracture: the Shanghai Changfeng
      Study.
AB  - We evaluated the relationship between a common polymorphism rs1800247 in
      osteocalcin gene and serum osteocalcin levels, bone mineral density and fracture
      in Chinese. This was a population-based cross-sectional study. We demonstrated
      that rs1800247 was associated with bone mineral density and fracture in men and
      serum osteocalcin levels in women. INTRODUCTION: This study aimed to evaluate the
      relationship between a common polymorphism rs1800247 in osteocalcin gene and
      serum total osteocalcin levels, bone mineral density (BMD) and fracture in
      Chinese middle-aged and elderly men and women. METHODS: This was a population
      based cross-sectional study included 5561 individuals aged 45 years or older.
      Information on fractures sustained after age of 45 were collected. BMD at the
      lumbar spine, femoral neck and total hip were measured using dual-energy X-ray
      absorptiometry. The genotyping of rs1800247 was performed by matrix-assisted
      laser desorption/ionization time-of-flight mass spectroscopy. RESULTS: rs1800247
      was associated with lumbar spine BMD and femoral neck BMD in the dominant model
      adjusted for age, body mass index (BMI), serum total osteocalcin in men (both P =
      0.04). Besides, rs1800247 was associated with fracture adjusted for age, BMI,
      serum total osteocalcin and total hip BMD in the additive and dominant models in
      men (P = 0.04 and 0.01). In the dominant model, the carriers of CC and TC
      genotypes was associated with a lower odds of fracture compared with the carriers
      of TT genotype (OR = 0.60, 95%CI 0.40-0.88, P = 0.01). In men, rs1800247 was not
      associated with serum total osteocalcin levels in additive, dominant or recessive
      models. However, rs1800247 was associated with serum total osteocalcin levels in
      all models adjusted for age, BMI, menopausal status and total hip BMD in women
      (all p < 0.001), with osteocalcin levels decreasing across TT, TC and CC
      genotypes. rs1800247 was not associated with BMD or fracture in all models in
      women. CONCLUSIONS: A common polymorphism rs1800247 in osteocalcin gene may
      affect the risk of osteoporosis and fracture and serum total osteocalcin levels
      in Chinese, and there may be gender differences underlying these associations.

PMID- 26194494
TI  - Erratum to: The utility of lumbar spine trabecular bone score and femoral neck
      bone mineral density for identifying asymptomatic vertebral fractures in well
      compensated type 2 diabetic patients.

PMID- 26194496
TI  - The microRNA-325 inhibits hepatocellular carcinoma progression by targeting high
      mobility group box 1.
AB  - BACKGROUND: MicroRNAs (miRNAs) can serve as tumor suppressors and might provide
      an efficient strategy for annihilating tumor cells. Nevertheless, the potential
      role of miR-325 in hepatocellular carcinoma (HCC) is still unknown. METHODS:
      Using RT-PCR, immunoblots invasion assays and bioinformatics strategies, we
      investigated the potential role of miR-325 in HCC. RESULTS: We showed that miR
      325 was decreased and HMGB1 was increased in 99 patients with hepatocellular
      carcinoma. MiR-325 inhibition promoted cell invasion and proliferation, while miR
      325 upregulation inhibited cell invasion and proliferation by using transwell and
      CCK8 assays. We further showed that HMGB1 might be a direct target of miR-325 and
      is negatively regulated by miR-325. Down-regulation of miR-325 predicts poor
      prognosis for HCC patients. CONCLUSIONS: These findings implied that miR-325
      regulates cell invasion and proliferation via targeting HMGB1 and may be a
      potential prognostic marker for HCC. VIRTUAL SLIDES: The virtual slide(s) for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/4655707031717989.

PMID- 26194497
TI  - Development of transgenic wheat (Triticum aestivum L.) expressing avidin gene
      conferring resistance to stored product insects.
AB  - BACKGROUND: Wheat is considered the most important cereal crop all over the
      world. The wheat weevil Sitophilus granarius is a serious insect pests in much of
      the wheat growing area worldwide and is responsible for significant loss of
      yield. Avidin proteins has been proposed to function as plant defense agents
      against insect pests. RESULTS: A synthetic avidin gene was introduced into spring
      wheat (Triticum aestivum L.) cv. Giza 168 using a biolistic bombardment protocol.
      The presence and expression of the transgene in six selected T0 transgenic wheat
      lines were confirmed at the molecular level. Accumulation of avidin protein was
      detected in transgenic plants compared to non-transgenic plants. Avidin transgene
      was stably integrated, transcribed and translated as indicated by Southern blot,
      ELISA, and dot blot analyses, with a high level of expression in transgenic wheat
      seeds. However, no expression was detected in untransformed wheat seeds.
      Functional integrity of avidin was confirmed by insect bioassay. The results of
      bioassay using transgenic wheat plants challenged with wheat weevil revealed 100
      % mortality of the insects reared on transgenic plants after 21 days. CONCLUSION:
      Transgenic wheat plants had improved resistance to Sitophilus granarius.

PMID- 26194495
TI  - Circulating monocytes: an appropriate model for bone-related study.
AB  - Peripheral blood monocytes (PBMs) are an important source of precursors of
      osteoclasts, the bone-resorbing cells and the cytokines produced by PBMs that
      have profound effects on osteoclast differentiation, activation, and apoptosis.
      So PBMs represent a highly valuable and unique working cell model for bone
      related study. Finding an appropriate working cell model for clinical and (epi
      )genomic studies of human skeletal disorders is a challenge. Peripheral blood
      monocytes (PBMs) can give rise to osteoclasts, the bone-resorbing cells.
      Particularly, PBMs provide the sole source of osteoclast precursors for adult
      peripheral skeleton where the bone marrow is normally hematopoietically inactive.
      PBMs can secrete potent pro- and anti-inflammatory cytokines, which are important
      for osteoclast differentiation, activation, and apoptosis. Reduced production of
      PBM cytokines represents a major mechanism for the inhibitory effects of sex
      hormones on osteoclastogenesis and bone resorption. Abnormalities in PBMs have
      been linked to various skeletal disorders/traits, strongly supporting for the
      biological relevance of PBMs with bone metabolism and disorders. Here, we briefly
      review the origin and further differentiation of PBMs. In particular, we discuss
      the close relationship between PBMs and osteoclasts, and highlight the utility of
      PBMs in study the pathophysiological mechanisms underlying various skeletal
      disorders. 

PMID- 26194498
TI  - Vitamin D deficiency in adult fracture patients: prevalence and risk factors.
AB  - PURPOSE: Although vitamin D levels are not routinely monitored in outpatient
      fracture patients, identification of fracture patients with a deficient vitamin D
      status may be clinically relevant because of the potential role of vitamin D in
      fracture healing. This study aimed to determine the prevalence of and risk
      factors for vitamin D deficiency in non-operatively treated adult fracture
      patients. PATIENTS AND METHODS: Vitamin D levels were determined in a cross
      sectional study of adult patients, who were treated non-operatively for a
      fracture of the upper or lower extremity in the outpatient clinic of a level 1
      trauma center, during one calendar year. Potential risk factors for (severe)
      vitamin D deficiency were analyzed using multivariable logistic regression
      analysis. RESULTS: A total of 208 men and 319 women with a mean age of 49.7 years
      (SD 19.9) were included. In this population, 71 % had a serum calcidiol <75
      nmol/L, 40 % were vitamin D deficient (serum calcidiol <50 nmol/L) and 11 % were
      severely vitamin D deficient (serum calcidiol <25 nmol/L). Smoking and season
      (winter and spring) were independent risk factors for vitamin D deficiency. An
      increasing age, a non-Caucasian skin type, winter and smoking were identified as
      independent risk factors for severe vitamin D deficiency. The use of vitamin D,
      alcohol consumption and higher average daily sun exposure were independent
      protective factors against (severe) vitamin D deficiency. CONCLUSION: Given the
      potential role of vitamin D in fracture healing, clinicians treating adult
      fracture patients should be aware of the frequent presence of vitamin D
      deficiency during the winter, especially in smoking and non-Caucasian patients.
      Research on the effect of vitamin D deficiency or supplementation on fracture
      healing is needed, before suggesting routine monitoring or supplementation.

PMID- 26194499
TI  - Unconscious trauma patients: outcome differences between southern Finland and
      Germany-lesson learned from trauma-registry comparisons.
AB  - PURPOSE: International trauma registry comparisons are scarce and lack
      standardised methodology. Recently, we performed a 6-year comparison between
      southern Finland and Germany. Because an outcome difference emerged in the
      subgroup of unconscious trauma patients, we aimed to identify factors associated
      with such difference and to further explore the role of trauma registries for
      evaluating trauma-care quality. METHODS: Unconscious patients [Glasgow Coma Scale
      (GCS) 3-8] with severe blunt trauma [Injury Severity Score (ISS) >=16] from
      Helsinki University Hospital's trauma registry (TR-THEL) and the German Trauma
      Registry (TR-DGU) were compared from 2006 to 2011. The primary outcome measure
      was 30-day in-hospital mortality. Expected mortality was calculated by Revised
      Injury Severity Classification (RISC) score. Patients were separated into
      clinically relevant subgroups, for which the standardised mortality ratios (SMR)
      were calculated and compared between the two trauma registries in order to
      identify patient groups explaining outcome differences. RESULTS: Of the 5243
      patients from the TR-DGU and 398 from the TR-THEL included, nine subgroups were
      identified and analyzed separately. Poorer outcome appeared in the Finnish
      patients with penetrating head injury, and in Finnish patients under 60 years
      with isolated head injury [TR-DGU SMR = 1.06 (95 % CI = 0.94-1.18) vs. TR-THEL
      SMR = 2.35 (95 % CI = 1.20-3.50), p = 0.001 and TR-DGU SMR = 1.01 (95 % CI = 0.87
      1.16) vs. TR-THEL SMR = 1.40 (95 % CI = 0.99-1.81), p = 0.030]. A closer analysis
      of these subgroups in the TR-THEL revealed early treatment limitations due to
      their very poor prognosis, which was not accounted for by the RISC. CONCLUSION:
      Trauma registry comparison has several pitfalls needing acknowledgement: the
      explanation for outcome differences between trauma systems can be a coincidence,
      a weakness in the scoring system, true variation in the standard of care, or
      hospitals' reluctance to include patients with hopeless prognosis in registry. We
      believe, however, that such comparisons are a feasible method for quality
      control.

PMID- 26194500
TI  - Description of two waterborne disease outbreaks in France: a comparative study
      with data from cohort studies and from health administrative databases.
AB  - Waterborne disease outbreaks (WBDO) of acute gastrointestinal illness (AGI) are a
      public health concern in France. Their occurrence is probably underestimated due
      to the lack of a specific surveillance system. The French health insurance
      database provides an interesting opportunity to improve the detection of these
      events. A specific algorithm to identify AGI cases from drug payment
      reimbursement data in the health insurance database has been previously
      developed. The purpose of our comparative study was to retrospectively assess the
      ability of the health insurance data to describe WBDO. Data from the health
      insurance database was compared with the data from cohort studies conducted in
      two WBDO in 2010 and 2012. The temporal distribution of cases, the day of the
      peak and the duration of the epidemic, as measured using the health insurance
      data, were similar to the data from one of the two cohort studies. However,
      health insurance data accounted for 54 cases compared to the estimated 252 cases
      accounted for in the cohort study. The accuracy of using health insurance data to
      describe WBDO depends on the medical consultation rate in the impacted
      population. As this is never the case, data analysis underestimates the total
      number of AGI cases. However this data source can be considered for the
      development of a detection system of a WBDO in France, given its ability to
      describe an epidemic signal. 

PMID- 26194501
TI  - Injury risk is low among world-class volleyball players: 4-year data from the
      FIVB Injury Surveillance System.
AB  - BACKGROUND: Little is known about the rate and pattern of injuries in
      international volleyball competition. OBJECTIVE: To describe the risk and pattern
      of injuries among world-class players based on data from the The International
      Volleyball Federation (FIVB) Injury Surveillance System (ISS) (junior and senior,
      male and female). METHODS: The FIVB ISS is based on prospective registration of
      injuries by team medical staff during all major FIVB tournaments (World
      Championships, World Cup, World Grand Prix, World League, Olympic Games). This
      paper is based on 4-year data (September 2010 to November 2014) obtained through
      the FIVB ISS during 32 major FIVB events (23 senior and 9 junior). RESULTS: The
      incidence of time-loss injuries during match play was 3.8/1000 player hours (95%
      CI 3.0 to 4.5); this was greater for senior players than for junior players
      (relative risk: 2.04, 1.29 to 3.21), while there was no difference between males
      and females (1.04, 0.70 to 1.55). Across all age and sex groups, the ankle was
      the most commonly injured body part (25.9%), followed by the knee (15.2%),
      fingers/thumb (10.7%) and lower back (8.9%). Injury incidence was greater for
      centre players and lower for liberos than for other player functions; injury
      patterns also differed between player functions. CONCLUSIONS: Volleyball is a
      very safe sport, even at the highest levels of play. Preventive measures should
      focus on acute ankle and finger sprains, and overuse injuries in the knee, lower
      back and shoulder.

PMID- 26194502
TI  - Is there a role for segmental adrenal venous sampling and adrenal sparing surgery
      in patients with primary aldosteronism?
AB  - OBJECTIVE AND DESIGN: Adrenal venous sampling (AVS) is critical to determine the
      subtype of primary aldosteronism (PA). Central AVS (C-AVS)--that is, the
      collection of effluents from bilateral adrenal central veins (CV)--sometimes does
      not allow differentiation between bilateral aldosterone-producing adenomas (APA)
      and idiopathic hyperaldosteronism. To establish the best treatment course, we
      have developed segmental AVS (S-AVS); that is, we collect effluents from the
      tributaries of CV to determine the intra-adrenal sources of aldosterone
      overproduction. We then evaluated the clinical utility of this novel approach in
      the diagnosis and treatment of PA. METHODS: We performed C-AVS and/or S-AVS in
      297 PA patients and assessed the accuracy of diagnosis based on the results of C
      AVS (n=138, 46.5%) and S-AVS (n=159, 53.5%) by comparison with those of
      clinicopathological evaluation of resected specimens. RESULTS: S-AVS demonstrated
      both elevated and attenuated secretion of aldosterone from APA and non-tumorous
      segments, respectively, in patients with bilateral APA and recurrent APA. These
      findings were completely confirmed by detailed histopathological examination
      after surgery. S-AVS, but not C-AVS, also served to identify APA located distal
      from the CV. CONCLUSIONS: Compared to C-AVS, S-AVS served to identify APA in some
      patients, and its use should expand the pool of patients eligible for adrenal
      sparing surgery through the identification of unaffected segments, despite the
      fact that S-AVS requires more expertise and time. Especially, this new technique
      could enormously benefit patients with bilateral or recurrent APA because of the
      preservation of non-tumorous glandular tissue.

PMID- 26194505
TI  - Health professionals: be prepared for heatwaves.

PMID- 26194503
TI  - Estimated glomerular filtration rate by serum cystatin C correlates with
      cardiometabolic parameters in patients with primary hyperparathyroidism.
AB  - OBJECTIVE: Patients with primary hyperparathyroidism (PHPT) are at risk of
      chronic kidney disease (CKD). Cystatin C (Cys-C) is considered a more reliable
      tool to assess glomerular filtration rate (GFR) than creatinine. The study aimed
      to assess circulating Cys-C and its relationships with biochemical PHPT and
      cardiometabolic parameters. DESIGN AND METHODS: The present cross-sectional study
      was performed in academic endocrine units on PHPT patients (n=190) and non
      hypertensive, non-diabetic, age- and sex-matched healthy controls (n=135) with no
      established CKD. The main outcomes were creatinine by alkaline picrate method,
      Cys-C by immunonephelometry and calculation of estimated GFR based on creatinine
      and Cys-C (eGFRcr-cys) using the CKD-EPI equation. RESULTS: In PHPT patients,
      circulating Cys-C ranged 0.45-3.13  mg/l and correlated with creatinine, age and
      BMI. Mean Cys-C level was higher in PHPT patients than in controls (0.93+/-0.02
      vs 0.78+/-0.14  mg/l; P=0.03). Cys-C levels in PHPT patients were predicted by
      age, BMI, ionized calcium, hypertension and HDL-cholesterol, the most significant
      determinant being ionized calcium. Cys-C positively correlated with
      cardiovascular disease (CVD) occurrence. Overall, 18.4% of PHPT patients with
      eGFRcr >60  ml/min per 1.73  m(2) (n=169) had Cys-C levels higher than the 95th
      percentile in controls (1.03  mg/l), consistent with a preclinical CKD, which was
      associated with hypertension and insulin resistance. Considering eGFRcr-cys, CKD
      (stages G3a, G3b, 4) was diagnosed in 13.7% of PHPT patients. Estimated GFRcr
      cys, but not eGFR based on creatinine, was predicted by insulin resistance and
      hypertension and positively correlated with CVD. CONCLUSIONS: Elevated Cys-C
      levels were associated with ionized calcium, cardiometabolic risk factors and
      CVD, and identified preclinical CKD in PHPT patients.

PMID- 26194506
TI  - Medicare opens up the end-of-life conversation.

PMID- 26194504
TI  - Is idiopathic hirsutism (IH) really idiopathic? mRNA expressions of skin
      steroidogenic enzymes in women with IH.
AB  - OBJECTIVE: Hirsutism results from hyperandrogenemia and/or exaggerated androgen
      responsiveness. Among various causes of hirsutism, some patients do not exhibit
      androgen excess which is called idiopathic hirsutism (IH). The pathogenesis of IH
      could not so far be clearly established. DESIGN: To investigate the mRNA
      expression of aromatase enzyme and the other enzymes having functional roles in
      the steroidogenic pathway, in freshly obtained skin tissue from subumbilical skin
      and the arm of the patients with IH and healthy women. METHODS: Twenty-one women
      with IH and 15 healthy women were included in the study. We aimed to determine
      mRNA expressions of genes associated with local androgen synthesis and metabolism
      (CYP11A1, STS, CYP19A1, SRD5A1, SRD5A2, HSD3B1, AR, COMT, ESR1, ESR2, HSD3B2,
      CYP17A1, SULT2A1, SULT1E1, HSD17B2, IL6, TGFB1, TNFA) from skin biopsy and blood
      samples of patients with IH and the data compared with healthy subjects. RESULTS:
      Patients with IH exhibit significantly lower interleukin 6 (IL6) mRNA expression
      and higher steroid sulphatase (STS) and hydroxysteroid (17beta) dehydrogenase 2
      (HSD17B2), gene mRNA expression, respectively, in the subumbilical region skin
      biopsies. Similarly, patients with IH exhibit significantly lower IL6 mRNA
      expression and higher STS and HSD17B2 gene mRNA expression, respectively, in the
      arm skin compared to healthy women's subumbilical region. CONCLUSIONS: In both
      arm and subumbilical skin biopsy of patients with IH, we observed an up
      regulation of HSD17B2 and STS, decreased IL6 mRNA expression, probably
      determining an increase in the local amount of active androgens, which could then
      be used as substrate for other androgen metabolic routes.

PMID- 26194507
TI  - Addressing opioid drug misuse in America.

PMID- 26194508
TI  - Measuring the SDGs: a two-track solution.

PMID- 26194510
TI  - Russia's war on drugs leaves patients without pain relief.

PMID- 26194511
TI  - Morocco debates liberalisation of abortion.

PMID- 26194512
TI  - Profile: The Liggins Institute, New Zealand.

PMID- 26194516
TI  - Wayne Cutfield: putting the spotlight on early life development.

PMID- 26194517
TI  - Care: in search of a health agenda.

PMID- 26194518
TI  - McLeod Ernest Chitiyo.

PMID- 26194519
TI  - Zika virus: following the path of dengue and chikungunya?

PMID- 26194520
TI  - P2X3 receptor antagonist in chronic cough--Authors' reply.

PMID- 26194521
TI  - P2X3 receptor antagonist in chronic cough.

PMID- 26194522
TI  - Discrimination against people with hepatitis B in China.

PMID- 26194523
TI  - Mobilising the Campaign to End Fistula.

PMID- 26194524
TI  - Lessons taught by acute promyelocytic leukemia cure.

PMID- 26194525
TI  - A tale of two clubs.

PMID- 26194526
TI  - Department of Error.

PMID- 26194527
TI  - Department of Error.

PMID- 26194528
TI  - Photodynamic therapy utilizing liposomal ClAlPc in human melanoma 3D cell
      cultures.

PMID- 26194529
TI  - Atypical Presentation of Right Ventricular Outflow Tract Ventricular Tachycardia.
AB  - BACKGROUND: Ventricular tachycardia (VT) in the pediatric population is rare, has
      a wide differential diagnosis, and can present in numerous ways. In the absence
      of underlying heart disease, VT is considered idiopathic and is associated with
      an excellent prognosis. Right ventricular outflow tract ventricular tachycardia
      (RVOT-VT) represents the most common form of idiopathic VT. The differential
      diagnosis, mechanism, presentation, management, and prognosis of RVOT-VT in the
      pediatric population will be discussed. CASE REPORT: We report a case of RVOT-VT
      that was incidentally discovered in an 11-year-old girl during an emergency
      department workup for severe headache. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE
      OF THIS?: It is essential for emergency physicians to have an approach to
      pediatric VT and appreciate the wide range of potential presentations.
      Differentiating idiopathic VT, such as RVOT-VT, from more malignant forms of VT
      can be challenging and requires expert consultation for further diagnostic workup
      and management.

PMID- 26194530
TI  - The influence of intravesical administration of resiniferatoxin (RTX) on the
      chemical coding of sympathetic chain ganglia (SChG) neurons supplying the porcine
      urinary bladder.
AB  - Resiniferatoxin (RTX) is used as an experimental drug in therapy of neurogenic
      urinary bladder disorders. The present study investigated the chemical coding of
      sympathetic chain ganglia (SChG) neurons supplying porcine urinary bladder after
      intravesical RTX instillation. The SChG neurons were visualized with retrograde
      tracing method and their chemical profile was disclosed with double-labeling
      immunohistochemistry using antibodies against dopamine beta-hydroxylase (DbetaH;
      marker of noradrenergic neurons), neuropeptide Y (NPY), vasoactive intestinal
      polypeptide (VIP), somatostatin (SOM), galanin, Leu(5)-enkephalin and neuronal
      nitric oxide synthase (nNOS). It was found that in both the control (n = 5) and
      RTX-treated pigs (n = 5), the vast majority (90.4 +/- 2.8 and 89.7 +/- 2.3%,
      respectively) of FB-positive (FB+) nerve cells were DbetaH+. RTX instillation
      caused a decrease in the number of FB+/DbetaH+ neurons immunopositive to NPY
      (71.1 +/- 12.1 vs 43.2 +/- 6.7%), VIP (21.3 +/- 10.7 vs 5.3 +/- 4.3%) or SOM
      (16.5 +/- 4.6 vs 2.3 +/- 2.6%) and a distinct increase in the number of
      FB+/DbetaH+ neurons immunoreactive to nNOS (0.8 +/- 1 vs 5.3 +/- 1.9 %). The
      present study for the first time has provided some information that therapeutic
      effects of RTX on the mammalian urinary bladder can be partly mediated by SChG
      neurons.

PMID- 26194531
TI  - The response of ecosystem carbon fluxes to LAI and environmental drivers in a
      maize crop grown in two contrasting seasons.
AB  - The eddy correlation technique was used to investigate the influence of
      biophysical variables and crop phenological phases on the behaviour of ecosystem
      carbon fluxes of a maize crop, in two contrasting growing seasons. In 2009, the
      reduced water supply during the early growing stage limited leaf area expansion,
      thus negatively affecting canopy photosynthesis. The variability of gross primary
      production (GPP) and ecosystem respiration (R eco) was mainly explained by
      seasonal variation of leaf area index (LAI). The seasonal variation of R eco was
      positively influenced by soil temperatures (T soil) in 2008 but not in 2009. In
      2008, a contribution of both autotrophic and heterotrophic components to total R
      eco could be hypothesized, while during 2009, autotrophic respiration is supposed
      to be the most important component. Crop phenological phases affected the
      response of ecosystem fluxes to biophysical drivers. 

PMID- 26194532
TI  - [Protective effect of GnRH analogues on the reproductive capacity of women with
      neoplasia or autoimmune disease who require chemotherapy. Final results of a
      phase ii clinical trial].
AB  - BACKGROUND AND OBJECTIVE: In order to avoid the toxic effect of chemotherapy, it
      has been proposed to use GnRH agonist analogues (GnRHa) to inhibit the depletion
      of ovarian follicles. Nevertheless, there is controversy about its effectiveness.
      This clinical trial has been conducted with the aim to assess the protective
      effect of GnRH analogues on the reproductive capacity of women with malignancies
      or autoimmune diseases, which require chemotherapy. PATIENTS AND METHODS: Open
      phase ii single-center clinical trial. During chemotherapy, a total of 5 doses of
      GnRH antagonist analogue at a dose interval of 3 days and/or a monthly dose of
      GnRHa were administered. Hormonal determinations prior to the start of the CT
      treatment were conducted during treatment and at the end of it. RESULTS: The
      inclusion of patients was prematurely concluded when incorporating the
      determination of anti-Mullerian hormone (AMH) as a parameter for assessing the
      ovarian reserve. Out of 38 patients, 23 (60.5%, 95%CI 43.4-76.0) had AMH values
      below normal following completion of treatment. An intermediate analysis was
      carried out observing that while most patients were recovering the menstrual
      cycle (86.6% 95%CI 71.9-95.6), they had reduced levels of AMH. CONCLUSION:
      Although most patients recovered their menstrual cycles, the ovarian reserve,
      assessed by the concentration of AMH, decreased in many patients. Therefore, we
      can conclude that the concomitant treatment of chemotherapy and GnRH analogues
      does not preserve the loss of follicular ovarian reserve.

PMID- 26194533
TI  - The use of serum glial fibrillary acidic protein test as a promising tool for
      intracerebral hemorrhage diagnosis in Chinese patients and prediction of the
      short-term functional outcomes.
AB  - The objective of this study was to explore the efficacy of glial fibrillary
      acidic protein (GFAP) in differentiating intracerebral hemorrhage (ICH) from
      ischemic stroke (IS). Suspicious patients of acute stroke were screened and
      finally diagnosed by computed tomography and magnetic resonance imaging. Blood
      samples were collected within 2-6 h after onset of symptoms, and serum GFAP level
      was determined by ELISA assay. The functional outcome for the patients was
      determined by modified Rankin Scale (mRS) 90 days after onset of symptoms. 43 ICH
      patients and 65 IS patients were enrolled. GFAP concentration in ICH group was
      significantly higher than in IS group (p < 0.001). Significant correlation was
      found when comparing GFAP with National Institutes of Health Stroke Scale (NIHSS)
      (r = 0.418, p = 0.005) and hemorrhage volume (r = 0.840, p < 0.001) in ICH group,
      while such correlation was not observed in IS group. ROC analysis indicated that
      GFAP level at the cut-point of 0.7 ng/ml yielded an AUC of 0.901 (95 % CI 0.828
      0.950) with high sensitivity (86.0 %) and specificity (76.9 %) to differentiate
      ICH from IS. Patients with higher serum GFAP concentration in ICH group
      experienced poorer functional disability (r = 0.755, p < 0.001), while this
      phenomenon was not observed in IS group (r = -0.114, p = 0.368). ROC curve
      analysis found that GFAP level at the cut-point of 1.04 ng/ml yielded an AUC of
      0.936 (95 % CI 0.817-0.988) in identifying patients with poor functional outcome,
      at the sensitivity and specificity of 95.7 and 80.0 %, respectively. GFAP test is
      a promising technique for diagnosis of ICH from IS and prediction of short-term
      functional outcomes. 

PMID- 26194534
TI  - Molecularly based management of gliomas in clinical practice.
AB  - Histological subtyping and grading of malignancy are the cornerstone of the
      present World Health Organization (WHO) Classification of CNS tumors. However,
      among diffuse gliomas of the adult, patients with histologically identical tumors
      may have different outcomes. As the genomic analysis of these tumors has
      progressed, it has become clear that specific molecular features transcend
      histologically defined variants, and may become markers of prognostic and/or
      predictive value. At the present time, the number of molecular biomarkers with
      confirmed clinical relevance (MGMT promoter methylation, 1p/19q codeletion,
      IDH1/2 mutations) remains limited, but new technologies will hopefully provide
      new candidates requiring rigorous validation in well-designed clinical trials.

PMID- 26194535
TI  - Idiopathic pes cavus in adults is not associated with neurophysiological
      impairment in the lower limbs.
AB  - The nerve conduction characteristics of adults with idiopathic pes cavus/hammer
      toes have not been studied extensively. Among 2048 out-patients (59.5 +/- 13.9
      years) referring to a laboratory of Neurophysiology in Rome, we recruited 18
      patients with idiopathic pes cavus (61.3 +/- 12.5 years). Fifty-four age/sex
      matched controls were also studied. No nerve conduction differences were observed
      between patients with and without cavus foot (p > 0.05). The absence of deep
      tendon reflexes and slight muscle weakness and hypotrophy in the lower limbs were
      more common in subjects with cavus foot deformity than in controls (p < 0.001).
      Adult patients with idiopathic pes cavus/hammer toes do not differ from healthy
      controls from a neurophysiological standpoint, but they could show minor signs of
      clinical impairment, such as lower limb weakness, hypotrophy and areflexia.

PMID- 26194537
TI  - Population-based data on asthma and allergic disease call for advanced
      epidemiologic methods.

PMID- 26194536
TI  - A genetic study of the FMR1 gene in a Sardinian multiple sclerosis population.
AB  - Multiple sclerosis (MS) is a complex autoimmune disease originated from the
      interplay between genetic and environmental factors. An overlap of clinical and
      neuroradiological parameters has been described between MS and an adult-onset
      neurodegenerative disorder, the fragile-X-associated tremor/ataxia syndrome
      (FXTAS). This syndrome is caused by a trinucleotide premutation expansion of a
      CGG sequence in the 55-200 repeat range, which is located in the fragile-X mental
      retardation 1 (FMR1) gene. Female premutation carriers have an increased
      propensity for immune-mediated disorders. Recently, a case of co-occurrence of MS
      and FXTAS was reported. Assuming that the premutation expansion may play a role
      in the MS susceptibility, we evaluated its frequency in a cohort of MS patients
      from Sardinia, an island characterized by a very high frequency of MS. Nuclear
      DNA was extracted by standard methods, purified with bisulfite treatment and then
      amplified twice by PCR with specific primers. Microsatellite analysis was
      performed and emizogotic subjects were sequenced. Clinical data of patients were
      also collected. Only 1/755 MS patients exhibited the premutation expansion with a
      heterozygosis pattern (30/58). No pathogenic repeat expansions (>200 repeats)
      were found in the entire cohort. Repeats labeled as the gray zone (45-60 repeats)
      were observed in 15/755 patients. No specific clinical features concerning
      disease course, disease activity, and disability were reported for these
      patients. Our results do not support a possible role for premutation or gray zone
      alleles in MS Sardinian patients. Further studies are needed to better understand
      the relationship between FXTAS and MS.

PMID- 26194538
TI  - Platelet activation markers overexpressed specifically in patients with aspirin
      exacerbated respiratory disease.
AB  - BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by
      respiratory reactions on ingestion of COX-1 inhibitors and cysteinyl leukotriene
      overproduction. The hypersensitivity reaction is induced by low doses of aspirin
      that inhibit COX-1 in platelets. OBJECTIVE: We sought to explore the role of
      platelets in the pathogenesis of AERD in patients under stable conditions and
      during an aspirin challenge test. METHODS: Stable patients with AERD (n = 30),
      aspirin-tolerant asthma (ATA; n = 21), or idiopathic chronic eosinophilic
      pneumonia (n = 10) were enrolled. Platelet activation was estimated based on
      expression levels of P-selectin (CD62P), CD63, CD69, and GPIIb/IIIa (PAC-1) in
      peripheral platelets; percentages of circulating platelet-adherent leukocytes;
      and plasma levels of soluble P-selectin (sP-selectin) and soluble CD40 ligand
      (sCD40L). RESULTS: In the stable condition, expression of all surface markers on
      platelets, the percentage of platelet-adherent eosinophils, and the plasma levels
      of sP-selectin and sCD40L were significantly higher in patients with AERD
      compared with those in patients with ATA. P-selectin and CD63 expression on
      platelets and plasma sP-selectin and sCD40L levels were positively correlated
      with the percentage of platelet-adherent eosinophils. Among these markers, P
      selectin expression and plasma sP-selectin levels positively correlated with
      urinary concentrations of leukotriene E4. Additionally, plasma sP-selectin and
      sCD40L levels were negatively correlated with lung function. In contrast,
      platelet activation markers in patients with AERD did not change during the
      aspirin challenge test. CONCLUSION: Peripheral platelets were activated more in
      patients with stable AERD compared with those in patients with stable ATA,
      patients with idiopathic chronic eosinophilic pneumonia, and control subjects.
      Platelet activation was involved in cysteinyl leukotriene overproduction and
      persistent airflow limitations in patients with AERD.

PMID- 26194539
TI  - Evaluation of antithymocyte globulin pharmacokinetics and pharmacodynamics in
      children.

PMID- 26194540
TI  - Blood eosinophil counts predict treatment response in patients with severe
      eosinophilic asthma.

PMID- 26194541
TI  - Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic
      patients.
AB  - BACKGROUND: Patients with IgE-mediated cow's milk allergy who are nonreactive to
      baked milk (BM) can be desensitized with BM to promote tolerance to unheated milk
      (UM). OBJECTIVE: We sought to test whether patients who are BM reactive can
      progress in BM oral immunotherapy (OIT) and become desensitized to UM as well.
      METHODS: Fifteen patients (>4 years) who previously failed to complete our milk
      OIT program were enrolled into the BM OIT protocol. A dose of BM (180  degrees C
      for 30 minutes) which was less than the eliciting dose was increased 50% monthly
      while under medical supervision until the primary outcome dose of 1.3 g/d BM
      protein was achieved. Basophil reactivity and milk protein-specific IgE binding
      were analyzed at the first round of BM OIT therapy (T0) and at 12 months of BM
      treatment. RESULTS: In terms of the primary outcome, only 3 (21%) of 14 patients
      tolerated the 1.3 g/d BM dose. Although some patients initially progressed in BM
      OIT, 8 of 11 failed because of IgE-mediated reactions. Three did not complete the
      program because of non-IgE-mediated factors. An increase in challenge threshold
      to UM was noted in patients continuing until 12 months (P = .003), including
      those among whom reactions precluded continuation in the program. Patients (n =
      3) who successfully reached maintenance had decreased milk-specific IgE
      reactivity. Furthermore, the mean difference at T0 between induced HM and UM
      percentages of CD203c expression was significantly lower in patients who
      successfully completed BM OIT than in those who did not (-11% vs 4.4%, P =
      .0002), which is consistent with their decreased clinical reactivity to BM.
      CONCLUSIONS: Although use of hypoallergenic BM in OIT is a promising therapy,
      care must be taken before its administration in BM-reactive patients because of
      the risk for anaphylaxis and only limited increase in challenge threshold
      attained.

PMID- 26194543
TI  - Neonatal adiposity increases the risk of atopic dermatitis during the first year
      of life.
AB  - BACKGROUND: Early nutrition and adiposity have been linked to atopic dermatitis
      (AD) development. OBJECTIVE: We sought to describe risk factors for AD in the
      first year of life in infants participating in the Cork BASELINE birth cohort
      study (n = 1537). METHODS: Prospective data on early-life events, infant feeding,
      and nutritional and environmental exposures were collected at 15 weeks'
      gestation, birth, and 2, 6, and 12 months of age. Body composition was assessed
      by using air displacement plethysmography at day 2 and 2 months. The primary
      outcome, persistent AD, was determined if the U.K. Working Party Diagnostic
      Criteria were satisfied at both 6 and 12 months. RESULTS: At 6 and 12 months, the
      point prevalence of AD was 14.2% (99% CI, 10.5% to 17.8%) and 13.7% (99% CI,
      10.3% to 17.6%), respectively; 7.5% (99% CI, 5.0% to 9.9%) of infants had AD at
      both 6 and 12 months of age. At hospital discharge, 35% of infants were
      exclusively breast-fed, decreasing to 14% by 2 months. Complementary feeding was
      commenced at a median of 19 weeks (interquartile range, 17-22 weeks; 19% at <17
      weeks and 6% at >=26 weeks). Median fat mass at day 2 was 0.35 kg (interquartile
      range, 0.25-0.48 kg). A parental history of atopic disease was self-reported by
      43% of mothers and 34% of fathers. Risk factors for AD at 6 and 12 months were
      maternal atopy (adjusted odds ratio, 2.99; 99% CI, 1.35-6.59; P = .0004) and fat
      mass of the 80th percentile or greater at day 2 (adjusted odds ratio, 2.31; 99%
      CI, 1.02-2.25; P = .009). CONCLUSION: This is the first report of neonatal
      adiposity as a predictor of AD at 6 and 12 months of age in a well-characterized
      atopic disease-specific birth cohort.

PMID- 26194542
TI  - Defects of B-cell terminal differentiation in patients with type-1 Kabuki
      syndrome.
AB  - BACKGROUND: Kabuki syndrome (KS) is a complex multisystem developmental disorder
      associated with mutation of genes encoding histone-modifying proteins. In
      addition to craniofacial, intellectual, and cardiac defects, KS is also
      characterized by humoral immune deficiency and autoimmune disease, yet no
      detailed molecular characterization of the KS-associated immune phenotype has
      been reported. OBJECTIVE: We sought to characterize the humoral immune defects
      found in patients with KS with lysine methyltransferase 2D (KMT2D) mutations.
      METHODS: We comprehensively characterized B-cell function in a cohort (n = 13) of
      patients with KS (age, 4 months to 27 years). RESULTS: Three quarters (77%) of
      the cohort had a detectable heterozygous KMT2D mutation (50% nonsense, 20% splice
      site, and 30% missense mutations), and 70% of the reported mutations are novel.
      Among the patients with KMT2D mutations (KMT2D(Mut/+)), hypogammaglobulinemia was
      detected in all but 1 patient, with IgA deficiency affecting 90% of patients and
      a deficiency in at least 1 other isoform seen in 40% of patients. Numbers of
      total memory (CD27(+)) and class-switched memory B cells (IgM(-)) were
      significantly reduced in patients with KMT2D(Mut/+) mutations compared with
      numbers in control subjects (P < .001). Patients with KMT2D(Mut/+) mutations also
      had significantly reduced rates of somatic hypermutation in IgG (P = .003) but
      not IgA or IgM heavy chain sequences. Impaired terminal differentiation was noted
      in primary B cells from patients with KMT2D(Mut/+) mutations. Autoimmune
      pathology was observed in patients with missense mutations affecting the SET
      domain and its adjacent domains. CONCLUSIONS: In patients with KS, autosomal
      dominant KMT2D mutations are associated with dysregulation of terminal B-cell
      differentiation, leading to humoral immune deficiency and, in some cases,
      autoimmunity. All patients with KS should undergo serial clinical immune
      evaluations.

PMID- 26194544
TI  - Increased numbers of activated group 2 innate lymphoid cells in the airways of
      patients with severe asthma and persistent airway eosinophilia.
AB  - BACKGROUND: In patients with severe eosinophilic asthma, local maturation rather
      than systemic recruitment of mature cells might contribute to persistent airway
      eosinophilia. Group 2 innate lymphoid cells (ILC2s) are a major source of type 2
      cytokines (IL-5 and IL-13) and can facilitate eosinophilic inflammatory responses
      in mouse models of asthma in the absence of CD4+ lymphocytes. This study
      investigated the potential role of ILC2s in driving chronic airway eosinophilia
      in patients with severe asthma, despite regular high-dose oral corticosteroid
      therapy. METHODS: In a cross-sectional study we enumerated blood and sputum ILC2s
      (lin(-)CD45(+)127(+)ST2(+)) and levels of intracellular IL-5 and IL-13 in
      patients with severe asthma (n = 25), patients with steroid-naive mild atopic
      asthma (n = 19), and nonatopic control subjects (n = 5). Results were compared
      with numbers of CD4+ lymphocytes, eosinophil lineage-committed progenitors
      (eosinophilopoietic progenitor cells [EoPs]), and mature eosinophils. RESULTS:
      Significantly greater numbers of total and type 2 cytokine-producing ILC2s were
      detected in blood and sputum of patients with severe asthma compared to mild
      asthmatics. In contrast, intracellular cytokine expression by CD4 cells and EoPs
      within the airways did not differ between the asthmatic groups. In patients with
      severe asthma, although sputum CD4+ cells were more abundant than ILC2s and EoPs,
      proportionally, ILC2s were the predominant source of type 2 cytokines. In
      addition, there were significantly greater numbers of sputum IL-5(+)IL-13(+)
      ILC2s in patients with severe asthma whose airway eosinophilia was greater than
      3%, despite normal blood eosinophil numbers (<300/MUL). CONCLUSIONS: Our findings
      suggest that ILC2s can promote the persistence of airway eosinophilia in patients
      with severe asthma through uncontrolled localized production of the type 2
      cytokines IL-5 and IL-13, despite high-dose oral corticosteroid therapy.

PMID- 26194545
TI  - MicroRNA activation signature in patients with hemophagocytic lymphohistiocytosis
      and reversibility with disease-specific therapy.

PMID- 26194546
TI  - Comparison of risk factors for viral and nonviral asthma exacerbations.

PMID- 26194547
TI  - Altered expression of chemoattractant receptor-homologous molecule expressed on
      T(H)2 cells on blood basophils and eosinophils in patients with chronic
      spontaneous urticaria.

PMID- 26194548
TI  - Distinct transcriptome profiles differentiate nonsteroidal anti-inflammatory drug
      dependent from nonsteroidal anti-inflammatory drug-independent food-induced
      anaphylaxis.
AB  - BACKGROUND: Lipid transfer protein (LTP), an abundant protein in fruits,
      vegetables, and nuts, is a common food allergen in Mediterranean areas causing
      diverse allergic reactions. Approximately 40% of food-related anaphylaxis induced
      by LTPs requires nonsteroidal anti-inflammatory drugs (NSAIDs) as a triggering
      cofactor. OBJECTIVE: We sought to better understand the determinants of NSAID
      dependent and NSAID-independent LTP-induced anaphylaxis (LTP-A). METHODS:
      Selection of patients was based on a proved clinical history of NSAID-dependent
      or NSAID-independent anaphylaxis to LTPs, positive skin prick test response to
      LTPs, and serum LTP IgE. Whole-transcriptome (RNA sequencing) analysis of blood
      cells from 14 patients with NSAID-related LTP-A (NSAID-LTP-A), 7 patients with
      LTP-A, and 13 healthy control subjects was performed to identify distinct gene
      expression signatures. RESULTS: Expression of genes regulating gastrointestinal
      epithelial renewal was altered in both patient sets, particularly in those with
      LTP-A, who also presented with gene expression profiles characteristic of an
      inflammatory syndrome. These included altered B-cell pathways, increased
      neutrophil activation markers, and increased reactive oxygen species levels.
      Increased expression of the IgG receptor (CD64) in patients with LTP-A was
      mirrored by the presence of LTP-specific IgG1 and IgG3. Conversely, patients with
      NSAID-LTP-A were characterized by reduced expression of IFN-gamma-regulated genes
      and IFN-gamma levels, as well as upregulated expression of adenosine receptor 3
      (ADORA3) and genes related to adenosine metabolism. CONCLUSIONS: Gene ontology
      analysis suggests disturbances in gut epithelial homeostasis in both groups with
      LTP-A, with potential integrity breaches in patients with LTP-A that might
      explain their distinct inflammatory signatures. Differential regulation in
      patients with LTP-A and those with NSAID-LTP-A of the IFN-gamma pathway, IgG
      receptors, and ADORA3 might provide the pathogenic basis of their distinct
      responses.

PMID- 26194549
TI  - Viral myocarditis--diagnosis, treatment options, and current controversies.
AB  - Myocarditis--a frequent cause of dilated cardiomyopathy and sudden cardiac death-
      typically results from cardiotropic viral infection followed by active
      inflammatory destruction of the myocardium. Characterization of this disease has
      been hampered by its heterogeneous clinical presentations and diverse
      aetiologies. Advances in cardiac MRI and molecular detection of viruses by
      endomyocardial biopsy have improved our ability to diagnose and understand the
      pathophysiological mechanisms of this elusive disease. However, therapeutic
      options are currently limited for both the acute and chronic phases of
      myocarditis. Several randomized, controlled trials have demonstrated potential
      benefit with immunosuppressive and immunomodulatory therapies, but further
      investigations are warranted. In this Review, we explore the pathophysiology,
      natural history, and modes of diagnosis of myocarditis, as well as evidence-based
      treatment strategies. As novel imaging techniques and human in vitro models of
      the disease emerge, the landscape of therapies for myocarditis is poised to
      improve.

PMID- 26194550
TI  - Regulatory science: Trust and transparency in clinical trials of medical devices.

PMID- 26194551
TI  - Iron deficiency and cardiovascular disease.
AB  - Iron deficiency affects up to one-third of the world's population, and is
      particularly common in elderly individuals and those with certain chronic
      diseases. Iron excess can be detrimental in cardiovascular illness, and research
      has now also brought anaemia and iron deficiency into the focus of cardiovascular
      medicine. Data indicate that iron deficiency has detrimental effects in patients
      with coronary artery disease, heart failure (HF), and pulmonary hypertension, and
      possibly in patients undergoing cardiac surgery. Around one-third of all patients
      with HF, and more than one-half of patients with pulmonary hypertension, are
      affected by iron deficiency. Patients with HF and iron deficiency have shown
      symptomatic improvements from intravenous iron administration, and some evidence
      suggests that these improvements occur irrespective of the presence of anaemia.
      Improved exercise capacity has been demonstrated after iron administration in
      patients with pulmonary hypertension. However, to avoid iron overload and T-cell
      activation, it seems that recipients of cardiac transplantations should not be
      treated with intravenous iron preparations. 

PMID- 26194554
TI  - [Exfoliative zonulopathy leading to an inferior subluxation of the "caspular bag,
      caspular tension ring and intraocular lens" complex].

PMID- 26194553
TI  - Combined cytotoxic activity of an infectious, but non-replicative herpes simplex
      virus type 1 and plasmacytoid dendritic cells against tumour cells.
AB  - Malignant melanoma is an aggressive tumour of the skin with increasing incidence,
      frequent metastasis and poor prognosis. At the same time, it is an immunogenic
      type of cancer with spontaneous regressions. Most recently, the tumoricidal
      effect of plasmacytoid dendritic cells (pDC) and their capacity to overcome the
      immunosuppressive tumour microenvironment are being investigated. In this
      respect, we studied the effect of the infectious, but replication-deficient,
      herpes simplex virus 1 (HSV-1) d106S vaccine strain, which lacks essential
      immediate early genes, in pDC co-cultures with 11 melanoma cell lines. We
      observed a strong cytotoxic activity, inducing apoptotic and necrotic cell death
      in most melanoma cell lines. The cytotoxic activity of HSV-1 d106S plus pDC was
      comparable to the levels of cytotoxicity induced by natural killer cells, but
      required only a fraction of cells with effector : target ratios of 1 : 20 (P <
      0.05). The suppressive activity of cell-free supernatants derived from virus
      stimulated pDC was significantly neutralized using antibodies against the
      interferon-alpha receptor (P < 0.05). In addition to type I interferons, TRAIL
      and granzyme B contributed to the inhibitory effect of HSV-1 d106S plus pDC to a
      minor extent. UV-irradiated viral stocks were significantly less active than
      infectious particles, both in the absence and presence of pDC (P < 0.05),
      indicating that residual activity of HSV-1 d106S is a major component and
      sensitizes the tumour cells to interferon-producing pDC. Three leukaemic cell
      lines were also susceptible to this treatment, suggesting a general anti-tumour
      effect. In conclusion, the potential of HSV-1 d106S for therapeutic vaccination
      should be further evaluated in patients suffering from different malignancies. 

PMID- 26194555
TI  - [Bilateral chorio-retinal coloboma].

PMID- 26194552
TI  - Drug-induced proarrhythmia: risk factors and electrophysiological mechanisms.
AB  - Drug-induced ventricular tachyarrhythmias can be caused by cardiovascular drugs,
      noncardiovascular drugs, and even nonprescription agents. They can result in
      arrhythmic emergencies and sudden cardiac death. If a new arrhythmia or
      aggravation of an existing arrhythmia develops during therapy with a drug at a
      concentration usually considered not to be toxic, the situation can be defined as
      proarrhythmia. Various cardiovascular and noncardiovascular drugs can increase
      the occurrence of polymorphic ventricular tachycardia of the 'torsade de pointes'
      type. Antiarrhythmic drugs, antimicrobial agents, and antipsychotic and
      antidepressant drugs are the most important groups. Age, female sex, and
      structural heart disease are important risk factors for the occurrence of torsade
      de pointes. Genetic predisposition and individual pharmacodynamic and
      pharmacokinetic sensitivity also have important roles in the generation of
      arrhythmias. An increase in spatial or temporal dispersion of repolarization and
      a triangular action-potential configuration have been identified as crucial
      predictors of proarrhythmia in experimental models. These studies emphasized that
      sole consideration of the QT interval is not sufficient to assess the
      proarrhythmic risk. In this Review, we focus on important triggers of
      proarrhythmia and the underlying electrophysiological mechanisms that can enhance
      or prevent the development of torsade de pointes. 

PMID- 26194556
TI  - Crouzon syndrome: Ophthalmologic complications in an untreated adult patient.

PMID- 26194557
TI  - Production of ginseng saponins: elicitation strategy and signal transductions.
AB  - Ginseng is one of the most important plants in oriental medicine. The
      pharmacological effects of this medicinal herb are mostly correlated to the major
      bioactive triterpene saponin, called ginsenoside. Due to the long cultivation
      period of ginseng and increased ginsenoside level in aged root, we need to
      develop strategies to increase ginseng productivity in cell and tissue culture in
      a faster way. Elicitation is already considered to improve the yield of this
      valuable secondary metabolite; especially, different types, timings, and
      durations of elicitation could affect the ginsenoside production and
      heterogeneity. Activation of ginsenoside biosynthetic genes and ginsenoside
      accumulation mediated by elicitor-induced signaling molecules would be helpful
      for commercial production of individual ginsenosides. Jasmonic acid is the well
      known signaling molecule which mainly involved in ginsenoside accumulation.
      Ca(2+) spiking and reactive oxygen species, nitric oxide, and ethylene production
      are other messengers which mediate production of ginsenoside. This review
      highlights the elicitation strategies for production of the ginsenoside based on
      the principle of putative signal transduction pathways.

PMID- 26194558
TI  - Identification and application of ssDNA aptamers against H37Rv in the detection
      of Mycobacterium tuberculosis.
AB  - Microscopy of direct smear with the Ziehl-Neelsen stain is still broadly used in
      tuberculosis diagnosis. However, this method suffers from low specificity and is
      difficult to distinguish Mycobacterium tuberculosis (MTB) from nontuberculosis
      mycobacterial (NTM), since all mycobacterial species are positive in Ziehl
      Neelsen stain. In this study, we utilized whole cell SELEX to obtain species
      specific aptamers for increasing the specificity of MTB detection. Whole cell
      SELEX was performed in MTB reference strain H37Rv by two selection processes
      based on enzyme-linked plate or Eppendorf tube, respectively. To increase success
      rate of generating aptamers, the selection processes were systematically
      monitored to understand the dynamic evolution of aptamers against complex
      structure of target bacteria. Two preponderant groups and ten high-affinity
      aptamers were obtained by analyzing the dynamic evolution. Preponderant aptamer
      MA1 from group I showed relatively high binding affinity with apparent
      dissociation constant (KD value) of 12.02 nM. Sandwich ELISA assay revealed five
      aptamer combinations effectively bound MTB strains in preliminary evaluation,
      especially the combination based on aptamer MA2 (another preponderant aptamer
      from group II) and MA1. Further evaluated in many other strains, MA2/MA1
      combination effectively identified MTB from NTM or other pathogenic bacteria, and
      displayed the high specificity and sensitivity. Binding analysis of aptamer MA1
      or MA2 by fluorescence microscopy observation showed high binding reactivity with
      H37Rv, low apparent cross-reactivity with M. marinum, and no apparent cross
      reactivity with Enterobacter cloacae. Taken together, this study provides
      attractive candidate species-specific aptamers to effectively capture or
      discriminate MTB strains.

PMID- 26194559
TI  - Combining rational metabolic engineering and flux optimization strategies for
      efficient production of fumaric acid.
AB  - Fumaric acid is an important C4-dicarboxylic acid widely used in chemical, food,
      and pharmaceutical industries. Rational metabolic engineering together with flux
      optimization were performed for the development of an Escherichia coli strain
      capable of efficiently producing fumaric acid. The initial engineered strain,
      CWF4N overexpressing phosphoenolpyruvate carboxylase (PPC), produced 5.30 g/L of
      fumaric acid. Optimization of PPC flux by examining 24 types of synthetic PPC
      expression vectors further increased the titer up to 5.72 g/L with a yield of
      0.432 g/g.glucose. Overexpression of the succinate dehydrogenase complex
      (sdhCDAB) led to an increase in carbon yield up to 0.493 g/g.glucose. Based on
      this mutant strain, citrate synthase (CS) was combinatorially overexpressed and
      balanced with PPC using 48 types of synthetic expression vectors. As a result,
      6.24 g/L of fumaric acid was produced with a yield of 0.500 g/g.glucose. Fed
      batch culture of this final strain allowed production of 25.5 g/L of fumaric acid
      with a yield of 0.366 g/g.glucose. Deletion of the aspA gene encoding aspartase
      and supplementation of aspartic acid further increased the fumaric acid titer to
      35.1 g/L with a yield of 0.490 g/g.glucose.

PMID- 26194560
TI  - Does cup-cage reconstruction with oversized cups provide initial stability in THA
      for osteoporotic acetabular fractures?
AB  - BACKGROUND: The incidence of acetabular fractures in osteoporotic patients is
      increasing. Immediate total hip arthroplasty (THA) has potential advantages, but
      achieving acetabular component stability is challenging and, at early followup,
      reported revision rates for loosening are high. QUESTIONS/PURPOSES: This study
      measured acetabular component stability and the initial surface contact achieved
      between the acetabular component and unfractured region of the pelvis after THA
      using an oversized acetabular component and cup-cage reconstruction. METHODS:
      Between November 2011 and November 2013, we treated 40 acute acetabular fractures
      in patients older than 70 years of age. Of these, 12 (30%) underwent immediate
      THA using an oversized acetabular component with screws inserted only into the
      ilium and a cup-cage construct. Postoperatively all patients were mobilized
      without weightbearing restrictions. Indications for immediate THA after
      acetabular fractures were displaced articular comminution deemed unreducible.
      Eleven of the 12 were prospectively studied to evaluate the initial stability of
      the reconstructions using radiostereometric analysis. One of the patients died of
      a pulmonary embolism after surgery, and the remaining 10 (median age, 81 years;
      range, 72-86 years) were studied. Of these, five were analyzed at 1 year and five
      were analyzed at 2 years. Acetabular component migration was defined as
      acceptable if less than the limits for primary THA that predict later loosening
      (1.76 mm of proximal migration and 2.53 degrees  of sagittal rotation). The
      contact surface between the acetabular component and ilium in direct continuity
      with the sacroiliac joint, and the ischium and pubis in direct continuity with
      the symphysis pubis, was measured on postoperative CT scans. RESULTS: At 1 year
      the median proximal migration was 0.83 mm (range, 0.09-5.13 mm) and sagittal
      rotation was 1.3 degrees  (range, 0.1 degrees -7.4 degrees ). Three of the 10
      components had migration above the suggested limits for primary THA at 1 year
      postoperatively. The contact surface achieved at surgery between the acetabular
      component and pelvis ranged from 11 to 17 cm(2) (15%-27% of each component).
      CONCLUSIONS: The majority of acetabular components in this cohort were stable
      despite the small contact surface achieved between the component and pelvic bone.
      Three of 10 migrated in excess of the limits that predict later loosening in
      primary THA but it remains to be seen whether these limits apply to this selected
      group of frail osteoporotic patients. We continue to use this technique routinely
      to treat patients with the same indications, but since the analysis of these data
      we have added screw fixation of the acetabular component to the ischial
      tuberosity and the superior pubic ramus. LEVEL OF EVIDENCE: Level IV, therapeutic
      study.

PMID- 26194562
TI  - Endocrinology and art. A goiter at the court of Theodolinda, queen of the
      Lombards: a fifteenth-century painting.

PMID- 26194561
TI  - Lengthening With External Fixation Is Effective in Congenital Femoral Deficiency.
AB  - BACKGROUND: Treatment of congenital femoral deficiency is a complex, multistage
      protocol and a variety of strategies have been devised to address joint
      instability, limb length inequality, and deformities. Despite being an important
      part of the algorithmic approach to the overall treatment of patients with
      congenital femoral deficiency, a reproducible, safe, and functional treatment for
      femoral length discrepancy in patients with mild and moderate congenital femoral
      deficiency has not been reported. QUESTIONS/PURPOSES: (1) Does femoral
      lengthening by means of distraction osteogenesis, using a monolateral external
      fixator, result in effective lengthening without loss of hip or knee range of
      motion? (2) Does femoral lengthening cause an inhibition of femoral growth in
      patients with congenital femoral deficiency? (3) Do patients/families report
      satisfactory functional and emotional outcomes after undergoing femoral
      lengthening? (4) What proportion of patients develops complications after femoral
      lengthening with this technique? METHODS: Between 2005 and 2009, we evaluated 38
      patients for femoral length discrepancy secondary to unilateral congenital
      femoral deficiency. Thirty-two patients completed treatment with distraction
      osteogenesis using a monolateral external fixator; general indications for this
      approach were congenital femoral deficiency Paley Types 1a, 1b, or 2a that had
      not previously undergone lengthening and had stable hip and knee joints. Of the
      32 patients that completed treatment, 30 (94%) were available at a minimum of 2
      years (mean, 3 years; range, 2-4.5 years) and were evaluated in this
      retrospective study. Preoperative and postoperative radiographic analysis,
      physiotherapy data, patient-based outcomes scores, and complications were
      reviewed for all eligible patients. Growth inhibition was measured using serial
      radiographs over the 2-year followup with the unaffected limb considered the
      norm. Functional and emotional outcomes were reported by adolescent patients or
      parents of younger children using the Pediatric Orthopaedic Society of North
      America Pediatric Outcomes Data Collection Instruments (PODCI), a validated
      patient-based outcomes measure. RESULTS: The mean distal femoral lengthening was
      6 cm (SD +/- 2 cm; range, 1.6-9 cm), for a mean percent of femoral length
      discrepancy correction of 112% (SD +/- 55%; range, 15%-215%). Comparison of
      patient preoperative with postoperative mean hip and knee flexion and extension
      showed no difference with the numbers available (hip flexion: p = 0.219, mean
      difference of -5, 95% confidence interval [CI], 10, SD = 20; hip extension: p =
      0.423, mean difference of -1, 95% CI, 2, SD = 5; knee flexion: mean difference of
      -7 degrees , SD +/- 29 degrees , CI, 15, p = 0.467; knee extension: mean
      difference of -1 degrees , SD +/- 9 degrees , CI, 4, p = 0.757). A comparison of
      the mean preoperative inhibition of 41% (range, -38% to 300%; SD +/- 72; 95% CI,
      29%) with the mean postoperative inhibition of 16% (range, -242% to 100%; SD +/-
      61%; 95% CI, 25%) for a mean postoperative stimulation of 25% (p = 0.055, SD +/-
      90%; 95% CI, 36%). In all six PODCI categories surveyed, patients had favorable
      standardized and normative scores, but patients who underwent femoral lengthening
      greater than 6 cm had both lower global functioning scores (90, SD +/- 10 versus
      96, SD +/- 3, p = 0.043) and worse pain/comfort scores (79, SD +/- 25 versus 96,
      SD +/- 7, p = 0.029), and patients who had mean percent femoral lengthening
      greater than 25% of initial femur length had worse pain/comfort scores (79, SD +/
      23 versus 97, SD +/- 4, p = 0.012) with similar global functioning scores (90,
      SD +/- 9 versus 96, SD +/- 3, p = 0.058). The total number of postsurgical
      complications was 30 in 60 planned surgical procedures (50%). CONCLUSIONS: Our
      study results support the use of the described surgical technique for femoral
      lengthening in treating patients with congenital femoral deficiency. Additional
      studies are needed both to follow long-term patient-reported outcome measures,
      especially after a second or third lengthening, and to determine the effect of
      serial lengthening on the stimulation or inhibition of growth and rate of
      complications. LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID- 26194563
TI  - Endocrinology and art: "The Annunciation"-Girolamo Francesco Maria Mazzola called
      Parmigianino (1503-1540).

PMID- 26194564
TI  - Sleepiness and Cognitive Performance among Younger and Older Adolescents across a
      28-Hour Forced Desynchrony Protocol.
AB  - STUDY OBJECTIVES: Quantify the homeostatic and circadian effects on sleepiness
      and performance of adolescents. Examine age-related changes in homeostatic and
      circadian regulation of sleepiness and performance by comparing younger and older
      adolescent groups. DESIGN: Three-week laboratory study including 12 cycles of a
      28-h forced desynchrony protocol. SETTING: Controlled laboratory environment with
      individual sleep and performance testing rooms and shared common areas.
      PARTICIPANTS: Twenty-seven healthy adolescents including 16 females. Ages ranged
      from 9.6-15.2 years and participants were split into younger (n = 14 ages 9-12)
      and older (n = 13 ages 13-15) groups based on median age split of 13.0 years.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Testing occurred every 2 h during
      scheduled wake periods. Measures included sleep latency during repeated nap
      opportunities and scores from a computerized neurobehavioral assessment battery
      including a 10-min psychomotor vigilance task, a digit symbol substitution task,
      and the Karolinska Sleepiness Scale. Significant main effects of circadian and
      homeostatic factors were observed, as well as several circadian and homeostatic
      interaction effects. Age group did not have a significant main effect on sleep
      and performance data. A significant interaction of circadian phase and age group
      was found for sleep latency, with younger adolescents showing greater circadian
      modulation than older teens during the circadian night. CONCLUSIONS: Adolescents
      demonstrated a similar pattern of response to forced desynchrony as reported for
      adults. Sleepiness and performance were affected by homeostatic and circadian
      factors, and age group did not interact with homoeostatic and circadian factors
      for subjective sleepiness and most performance metrics. Younger adolescents had a
      shorter latency to sleep onset than older during the circadian bin spanning 4 to
      8 h after the onset of melatonin secretion.

PMID- 26194565
TI  - Benefits of Sleep Extension on Sustained Attention and Sleep Pressure Before and
      During Total Sleep Deprivation and Recovery.
AB  - OBJECTIVES: To investigate the effects of 6 nights of sleep extension on
      sustained attention and sleep pressure before and during total sleep deprivation
      and after a subsequent recovery sleep. DESIGN: Subjects participated in two
      experimental conditions (randomized cross-over design): extended sleep (EXT, 9.8
      +/- 0.1 h (mean +/- SE) time in bed) and habitual sleep (HAB, 8.2 +/- 0.1 h time
      in bed). In each condition, subjects performed two consecutive phases: (1) 6
      nights of either EXT or HAB (2) three days in-laboratory: baseline, total sleep
      deprivation and after 10 h of recovery sleep. SETTING: Residential sleep
      extension and sleep performance laboratory (continuous polysomnographic
      recording). PARTICIPANTS: 14 healthy men (age range: 26-37 years). INTERVENTIONS:
      EXT vs. HAB sleep durations prior to total sleep deprivation. MEASUREMENTS AND
      RESULTS: Total sleep time and duration of all sleep stages during the 6 nights
      were significantly higher in EXT than HAB. EXT improved psychomotor vigilance
      task performance (PVT, both fewer lapses and faster speed) and reduced sleep
      pressure as evidenced by longer multiple sleep latencies (MSLT) at baseline
      compared to HAB. EXT limited PVT lapses and the number of involuntary microsleeps
      during total sleep deprivation. Differences in PVT lapses and speed and MSLT at
      baseline were maintained after one night of recovery sleep. CONCLUSION: Six
      nights of extended sleep improve sustained attention and reduce sleep pressure.
      Sleep extension also protects against psychomotor vigilance task lapses and
      microsleep degradation during total sleep deprivation. These beneficial effects
      persist after one night of recovery sleep.

PMID- 26194566
TI  - Sleep Dependent Memory Consolidation in Children with Autism Spectrum Disorder.
AB  - STUDY OBJECTIVES: Examine the role of sleep in the consolidation of declarative
      memory in children with autism spectrum disorder (ASD). DESIGN: Case-control
      study. SETTING: Home-based study with sleep and wake conditions. PARTICIPANTS:
      Twenty-two participants with ASD and 20 control participants between 9 and 16 y
      of age. MEASUREMENTS AND RESULTS: Participants were trained to criterion on a
      spatial declarative memory task and then given a cued recall test. Retest
      occurred after a period of daytime wake (Wake) or a night of sleep (Sleep) with
      home-based polysomnography; Wake and Sleep conditions were counterbalanced.
      Children with ASD had poorer sleep efficiency than controls, but other sleep
      macroarchitectural and microarchitectural measures were comparable after
      controlling for age and medication use. Both groups demonstrated better memory
      consolidation across Sleep than Wake, although participants with ASD had poorer
      overall memory consolidation than controls. There was no interaction between
      group and condition. The change in performance across sleep, independent of
      medication and age, showed no significant relationships with any specific sleep
      parameters other than total sleep time and showed a trend toward less forgetting
      in the control group. CONCLUSION: This study shows that despite their more
      disturbed sleep quality, children with autism spectrum disorder (ASD) still
      demonstrate more stable memory consolidation across sleep than in wake
      conditions. The findings support the importance of sleep for stabilizing memory
      in children with and without neurodevelopmental disabilities. Our results suggest
      that improving sleep quality in children with ASD could have direct benefits to
      improving their overall cognitive functioning.

PMID- 26194568
TI  - Evidence for a Possible Link between Bedtime and Change in Body Mass Index.
AB  - OBJECTIVES: The aim of the current study was to examine the longitudinal
      relationship between bedtimes and body mass index (BMI) from adolescence to
      adulthood in a nationally representative sample. DESIGN: Three waves of data from
      the National Longitudinal Study of Adolescent Health were used to assess the
      bedtimes and BMI of 3,342 adolescents between 1994 and 2009. Hypotheses were
      tested with hierarchical linear models using a two-level, random intercept and
      slopes model. RESULTS: Later average bedtime during the workweek, in hours, from
      adolescence to adulthood was associated with an increase in BMI over time (b =
      0.035 kg/m(2) per min later bedtime per 6 years; standard error = 0.016; t =
      2.12, degrees of freedom = 3,238, P < 0.05). These results remained significant
      after controlling for demographic characteristics and baseline BMI. Although
      sleep duration, screen time, and exercise frequency did not attenuate the
      relationship between workday bedtime and BMI over time, fast-food consumption was
      recognized as a significant partial mediator of the relationship between bedtimes
      and BMI longitudinally. CONCLUSIONS: The results highlight bedtimes as a
      potential target for weight management during adolescence and during the
      transition to adulthood.

PMID- 26194569
TI  - Interictal Hippocampal Spiking Influences the Occurrence of Hippocampal Sleep
      Spindles.
AB  - OBJECTIVES: The significance of hippocampal sleep spindles and their relation to
      epileptic activity is still a matter of controversy. Hippocampal spindles have
      been considered a physiological phenomenon, an evoked response to afferent
      epileptic discharges, or even the expression of an epileptic manifestation. To
      address this question, we investigated the presence and rate of hippocampal
      spindles in focal pharmacoresistant epilepsy patients undergoing scalp
      intracerebral electroencephalography (EEG). DESIGN: Sleep recording with scalp
      intracerebral EEG. SETTING: Tertiary referral epilepsy center. PATIENTS: Twenty
      five epilepsy patients (extratemporal: n = 6, temporal: n = 15, and multifocal
      including the temporal lobe: n = 4). INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: We analyzed associations between hippocampal spindles and hippocampal
      electrophysiological findings (interictal spiking, seizure onset zone) and
      magnetic resonance imaging volumetry. Sixteen of 25 patients (64%) had
      hippocampal spindles (extratemporal epilepsy: 6/6; temporal epilepsy: 10/15; and
      multifocal epilepsy: 0/4; P = 0.005). Median spindle rate was 0.6 (range, 0.1
      8.6)/min in nonrapid eye movement sleep. Highest spindle rates were found in
      hippocampi of patients with extratemporal epilepsy (P < 0.001). A negative
      association was found between hippocampal spiking activity and spindle rate (P =
      0.003). We found no association between the presence (n = 21) or absence (n = 17)
      of hippocampal seizure onset zone and hippocampal spindle rate (P = 0.114), and
      between a normal (n = 30) or atrophic (n = 8) hippocampus and hippocampal spindle
      rate (P = 0.195). CONCLUSIONS: Hippocampal spindles represent a physiological
      phenomenon, with an expression that is diminished in epilepsy affecting the
      temporal lobe. Hippocampal spiking lowered the rate of hippocampal spindles,
      suggesting that epileptic discharges may at least in part be a transformation of
      these physiological events, similar to the hypothesis considering generalized
      spike-and-waves a transformation of frontal spindles.

PMID- 26194567
TI  - Insomnia Caused by Serotonin Depletion is Due to Hypothermia.
AB  - STUDY OBJECTIVE: Serotonin (5-hydroxytryptamine, 5-HT) neurons are now thought to
      promote wakefulness. Early experiments using the tryptophan hydroxylase inhibitor
      para-chlorophenylalanine (PCPA) had led to the opposite conclusion, that 5-HT
      causes sleep, but those studies were subsequently contradicted by
      electrophysiological and behavioral data. Here we tested the hypothesis that the
      difference in conclusions was due to failure of early PCPA experiments to control
      for the recently recognized role of 5-HT in thermoregulation. DESIGN: Adult male
      C57BL/6N mice were treated with PCPA (800 mg/kg intraperitoneally for 5 d; n =
      15) or saline (n = 15), and housed at 20  degrees C (normal room temperature) or
      at 33  degrees C (thermoneutral for mice) for 24 h. In a separate set of
      experiments, mice were exposed to 4  degrees C for 4 h to characterize their
      ability to thermoregulate. MEASUREMENTS AND RESULTS: PCPA treatment reduced brain
      5-HT to less than 12% of that of controls. PCPA-treated mice housed at 20 
      degrees C spent significantly more time awake than controls. However, core body
      temperature decreased from 36.5  degrees C to 35.1  degrees C. When housed at 33 
      degrees C, body temperature remained normal, and total sleep duration, sleep
      architecture, and time in each vigilance state were the same as controls. When
      challenged with 4  degrees C, PCPA-treated mice experienced a precipitous drop in
      body temperature, whereas control mice maintained a normal body temperature.
      CONCLUSIONS: These results indicate that early experiments using para
      chlorophenylalanine that led to the conclusion that 5-hydroxytryptamine (5-HT)
      causes sleep were likely confounded by hypothermia. Temperature controls should
      be considered in experiments using 5-HT depletion.

PMID- 26194570
TI  - Early Blood Lead Levels and Sleep Disturbance in Preadolescence.
AB  - STUDY OBJECTIVES: Little is known about the effect of lead exposure on children's
      sleep. This study examined the association between blood lead levels (BLL) and
      sleep problems in a longitudinal study of children. SETTING: Four community-based
      elementary schools in Jintan City, China. PARTICIPANTS: 1,419 Chinese children.
      MEASUREMENT AND RESULTS: BLL were measured when children were aged 3-5 y, and
      sleep was assessed at ages 9-13 y. Sleep was assessed by both parents' report,
      using the Children's Sleep Habits Questionnaire (CSHQ), and children's report,
      using an adolescent sleep questionnaire. A total of 665 children with complete
      data on BLL and sleep at both ages were included in the current study. Mean age
      of the sample at BLL assessment was 4.74 y (standard deviation [SD] = 0.89) and
      at sleep assessment was 11.05 y (SD = 0.88). Mean BLL was 6.26 MUg/dL (SD =
      2.54). There were significant positive correlations between BLL and 3 CSHQ
      subscales: Sleep onset delay (r = 0.113, P < 0.01), sleep duration (r = 0.139, P
      < 0.001), and night waking (r = 0.089, P < 0.05). Excessive daytime sleepiness
      (EDS) (26.1% versus 9.0%, P < 0.001) and use of sleeping pills (6.5% versus 1.8%,
      P = 0.03) were more prevalent in children BLL >= 10.0 MUg/dL than in those
      children BLL < 10.0 MUg/dL. After adjusting for demographics, BLL >= 10.0 MUg/dL
      was significantly associated with increased risk for insomnia symptoms (odds
      ratio [OR] = 2.01, 95% confidence interval [CI] = 1.03-3.95) and EDS (OR = 2.90,
      95% CI = 1.27-6.61). CONCLUSION: The findings indicate that elevated blood lead
      levels in early childhood are associated with increased risk for sleep problems
      and excessive daytime sleepiness in later childhood.

PMID- 26194571
TI  - Parsing Race by Genetic Ancestry.

PMID- 26194572
TI  - Putting Some Teeth into It: Connecting Periodontitis with Sleep Apnea.

PMID- 26194573
TI  - Does Treatment of Sleep Apnea Prevent Perioperative Complications? Wish We Knew!

PMID- 26194574
TI  - Weaving the Internet of Sleep: The Future of Patient-Centric Collaborative Sleep
      Health Management Using Web-Based Platforms.

PMID- 26194575
TI  - Sleep Doesn't Waste Time, It's Good for the Waist Line.

PMID- 26194577
TI  - Experimental Sleep Restriction Facilitates Pain and Electrically Induced Cortical
      Responses.
AB  - STUDY OBJECTIVES: Sleep restriction (SR) has been hypothesized to sensitize the
      pain system. The current study determined whether experimental sleep restriction
      had an effect on experimentally induced pain and pain-elicited
      electroencephalographic (EEG) responses. DESIGN: A paired crossover study.
      INTERVENTION: Pain testing was performed after 2 nights of 50% SR and after 2
      nights with habitual sleep (HS). SETTING: Laboratory experiment at research
      center. PARTICIPANTS: Self-reported healthy volunteers (n = 21, age range: 18-31
      y). MEASUREMENTS AND RESULTS: Brief high-density electrical stimuli to the
      forearm skin produced pinprick-like pain. Subjective pain ratings increased after
      SR, but only in response to the highest stimulus intensity (P = 0.018). SR
      increased the magnitude of the pain-elicited EEG response analyzed in the time
      frequency domain (P = 0.021). Habituation across blocks did not differ between HS
      and SR. Event-related desynchronization (ERD) was reduced after SR (P = 0.039).
      Pressure pain threshold of the trapezius muscle region also decreased after SR (P
      = 0.017). CONCLUSION: Sleep restriction (SR) increased the sensitivity to
      pressure pain and to electrically induced pain of moderate, but not low,
      intensity. The increased electrical pain could not be explained by a difference
      in habituation. Increased response magnitude is possibly related to reduced
      processing within the somatosensory cortex after partial SR.

PMID- 26194578
TI  - Symptoms of Depression and Difficulty Initiating Sleep from Early Adolescence to
      Early Adulthood: A Longitudinal Study.
AB  - STUDY OBJECTIVES: To assess the direction of the relationship and degree of
      shared associations between symptoms of depression and difficulty initiating
      sleep (DIS) from early adolescence to early adulthood. DESIGN: Cross-sectional
      and longitudinal assessment of the symptoms of depression-DIS association from
      early adolescence (age 13 y) to early adulthood (age 23 y). SETTING: Hordaland,
      Norway. PARTICIPANTS: There were 1,105 individuals (55% male) who took part in
      the Norwegian Longitudinal Health Behaviour Study (NLHB) and participated at
      least once across seven data collection waves during the years 1990-2000.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Characteristic data were obtained
      during the first assessment. Symptoms of depression and instances of DIS were
      assessed during each data collection wave. Symptoms of depression and DIS were
      associated in all data waves, and one-step cross-lagged bivariate correlations
      were significant and comparatively high for both factors. Structural equation
      modelling indicated that DIS and symptoms of depression at wave 1 remain
      relatively stable across waves (all P < 0.001), and a significant and consistent
      unidirectional cross-lagged effect was noted running from symptoms of depression
      to DIS from early adolescence to early adulthood. DIS is only marginally and
      inconsistently associated with the lagged symptoms of depression score across
      waves. CONCLUSIONS: These results suggest that symptoms of depression established
      in early adolescence are a moderate predictor of difficulty initiating sleep
      (DIS) in early adulthood, whereas the reverse association of DIS predicting
      depression was not convincingly supported. These findings are in contrast to
      previous findings that suggest sleep problems as a risk factor for the later
      development of depression.

PMID- 26194580
TI  - From chemistry to biology database curation.

PMID- 26194579
TI  - Changes in Plasma Lipids during Exposure to Total Sleep Deprivation.
AB  - STUDY OBJECTIVES: The effects of sleep loss on plasma lipids, which play an
      important role in energy homeostasis and signaling, have not been systematically
      examined. Our aim was to identify lipid species in plasma that increase or
      decrease reliably during exposure to total sleep deprivation. DESIGN: Twenty
      individuals underwent sleep deprivation in a laboratory setting. Blood was drawn
      every 4 h and mass spectrometry techniques were used to analyze concentrations of
      263 lipid species in plasma, including glycerolipids, glycerophospholipids,
      sphingolipids, and sterols. SETTING: Chronobiology and Sleep Laboratory, Duke-NUS
      Graduate Medical School. PARTICIPANTS: Healthy ethnic-Chinese males aged 21-28 y
      (n = 20). INTERVENTIONS: Subjects were kept awake for 40 consecutive hours.
      MEASUREMENTS AND RESULTS: Each metabolite time series was modeled as a sum of
      sinusoidal (circadian) and linear components, and we assessed whether the slope
      of the linear component differed from zero. More than a third of all individually
      analyzed lipid profiles exhibited a circadian rhythm and/or a linear change in
      concentration during sleep deprivation. Twenty-five lipid species showed a linear
      and predominantly unidirectional trend in concentration levels that was
      consistent across participants. Choline plasmalogen levels decreased, whereas
      several phosphatidylcholine (PC) species and triacylglycerides (TAG) carrying
      polyunsaturated fatty acids increased. CONCLUSIONS: The decrease in choline
      plasmalogen levels during sleep deprivation is consistent with prior work
      demonstrating that these lipids are susceptible to degradation by oxidative
      stress. The increase in phosphatidylcholines and triacylglycerides suggests that
      sleep loss might modulate lipid metabolism, which has potential implications for
      metabolic health in individuals who do not achieve adequate sleep.

PMID- 26194581
TI  - Expanding opportunities for mining bioactive chemistry from patents.
AB  - Bioactive structures published in medicinal chemistry patents typically exceed
      those in papers by at least twofold and may precede them by several years. The
      Big-Bang of open automated extraction since 2012 has contributed to over 15
      million patent-derived compounds in PubChem. While mapping between chemical
      structures, assay results and protein targets from patent documents is
      challenging, these relationships can be harvested using open tools and are
      beginning to be curated into databases. 

PMID- 26194582
TI  - Target discovery from protein databases: challenges for curation.
AB  - Protein databases are a gold mine of potential new drug targets. The ready access
      to a complete overview of all aspects of protein biology provides the most
      benefit at the outset of drug discovery pipelines. Ideally, curation strategies
      used to move from the raw data to the validated knowledge should contain the
      checks and balances necessary for accuracy. The neXtProt human protein
      knowledgebase is used here as an example to give insight into these methods. 

PMID- 26194576
TI  - Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep
      Research Society on the Recommended Amount of Sleep for a Healthy Adult:
      Methodology and Discussion.
AB  - The American Academy of Sleep Medicine and Sleep Research Society recently
      released a Consensus Statement regarding the recommended amount of sleep to
      promote optimal health in adults. This paper describes the methodology,
      background literature, voting process, and voting results for the consensus
      statement. In addition, we address important assumptions and challenges
      encountered during the consensus process. Finally, we outline future directions
      that will advance our understanding of sleep need and place sleep duration in the
      broader context of sleep health.

PMID- 26194583
TI  - Chemical databases: curation or integration by user-defined equivalence?
AB  - There is a wealth of valuable chemical information in publicly available
      databases for use by scientists undertaking drug discovery. However finite
      curation resource, limitations of chemical structure software and differences in
      individual database applications mean that exact chemical structure equivalence
      between databases is unlikely to ever be a reality. The ability to identify
      compound equivalence has been made significantly easier by the use of the
      International Chemical Identifier (InChI), a non-proprietary line-notation for
      describing a chemical structure. More importantly, advances in methods to
      identify compounds that are the same at various levels of similarity, such as
      those containing the same parent component or having the same connectivity, are
      now enabling related compounds to be linked between databases where the structure
      matches are not exact. 

PMID- 26194584
TI  - Chemical biology databases: from aggregation, curation to representation.
AB  - Systems chemical biology offers a novel way of approaching drug discovery by
      developing models that consider the global physiological environment of protein
      targets and their perturbations by drugs. However, the integration of all these
      data needs curation and standardization with an appropriate representation in
      order to get relevant interpretations. In this mini review, we present some
      databases and services, which integrated together with computational tools and
      data standardization, could assist scientists in decision making during the
      different drug development process. 

PMID- 26194585
TI  - Reporting biological assay screening results for maximum impact.
AB  - A very large corpus of biological assay screening results exist in the public
      domain. The ability to compare and analyze this data is hampered due to missing
      details and lack of a commonly used terminology to describe assay protocols and
      assay endpoints. Minimum reporting guidelines exist that, if followed, would
      greatly enhance the utility of biological assay screening data so it may be
      independently reproduced, readily integrated, effectively compared, and rapidly
      analyzed. 

PMID- 26194586
TI  - Medicinal chemistry in the era of big data.
AB  - In the era of big data medicinal chemists are exposed to an enormous amount of
      bioactivity data. Numerous public data sources allow for querying across medium
      to large data sets mostly compiled from literature. However, the data available
      are still quite incomplete and of mixed quality. This mini review will focus on
      how medicinal chemists might use such resources and how valuable the current data
      sources are for guiding drug discovery. 

PMID- 26194587
TI  - The Role of Neighborhood in the Development of Aggression in Urban African
      American Youth: A Multilevel Analysis.
AB  - The purpose of this study was to examine the role of neighborhood disadvantage
      and perceptions of neighborhood on the development of aggressive behavior among a
      sample of urban low-income African American middle school aged youth (mean age =
      11.65 years). Results of hierarchical linear modeling indicated that youth
      experienced significant changes in rates of aggression across the three middle
      school years, and that on average, negative youth perceptions of neighborhood
      predicted increases in aggression. Both parent and youth perceptions of
      neighborhood disadvantage trended toward significance as a moderator between
      objective neighborhood characteristics and aggression. These results are in
      accordance with past research, which suggests that personal evaluations of the
      disadvantage of a neighborhood influence child development and behavior. Future
      studies should examine the role that perceptions play in youth development, as
      well as in interventions geared towards thwarting youth aggression. 

PMID- 26194588
TI  - Predicting Bystander Behavior to Prevent Sexual Assault on College Campuses: The
      Role of Self-Efficacy and Intent.
AB  - Bystander intervention has been increasingly applied to prevent sexual violence
      on college campuses. Its underlying theory assumes unidirectional relationships
      between variables, predicting that bystander behaviors (i.e., actions taken to
      intervene in sexual violence situations) will be influenced by bystander
      intentions (BI; i.e., likelihood to intervene in the future), which in turn will
      be affected by bystander efficacy (BE; i.e., confidence to intervene). One
      question for theory is whether a reciprocal relationship exists between BI and
      BE. We used structural equation modeling (SEM) with longitudinal data to test
      unidirectional and reciprocal causal relations between BI and BE. Participants (n
      = 1390) were students at a northeastern US university. Four models were examined
      using SEM: (1) a baseline model with autoregressive paths; (2) a model with
      autoregressive effects and BI predicting future BE; (3) a model with
      autoregressive effects and BE predicting future BI; and, (4) a fully cross-lagged
      model. Results indicated that reciprocal causality was found to occur between BI
      and BE. In addition, a final model demonstrated indirect effects of a bystander
      intervention program on bystander behaviors through both BI and BE at different
      time points. Implications for theory and practice are described, and directions
      for future research discussed. 

PMID- 26194589
TI  - Evaluation of the orbit using contrast-enhanced radial 3D fat-suppressed T1
      weighted gradient echo (Radial-VIBE) sequence.
AB  - OBJECTIVE: Contrast-enhanced fat-suppressed T1 weighted (T1W) two-dimensional
      (2D) turbo spin echo (TSE) and magnetization-prepared gradient echo (MPRAGE)
      sequences with water excitation are routinely obtained to evaluate orbit
      pathology. However, these sequences can be marred by artefacts. The radial-volume
      interpolated breath-hold examination (VIBE) sequence is a motion-robust fat
      suppressed T1W sequence which has demonstrated value in paediatric and body
      imaging. The purpose of our study was to evaluate its role in assessing the orbit
      and to compare it with routinely acquired sequences. METHODS: A Health Insurance
      Portability and Accountability Act-compliant and institutional review board
      approved retrospective study was performed in 46 patients (age range: 1-81 years)
      who underwent orbit studies on a 1.5-T MRI system using contrast-enhanced Radial
      VIBE, MPRAGE and 2D TSE sequences. Two radiologists blinded to the sequence
      analysed evaluated multiple parameters of image quality including motion
      artefact, degree of fat suppression, clarity of choroidal enhancement,
      intraorbital vessels, extraocular muscles, optic nerves, brain parenchyma and
      evaluation of pathology. Each parameter was assessed on a 5-point scale, with a
      higher score indicating the more optimal examination. Mix model analysis of
      variance and interobserver variability were assessed. RESULTS: Radial-VIBE
      demonstrated superior quality (p < 0.001) for all orbit parameters when compared
      with MPRAGE and 2D TSE. Interobserver agreement demonstrated average fair-to-good
      agreement for degree of motion artefact (0.745), fat suppression (0.678), clarity
      of choroidal enhancement (0.688), vessels (0.655), extraocular muscles (0.675),
      optic nerves (0.518), brain parenchyma (0.710) and evaluation of pathology
      (0.590). CONCLUSION: Radial-VIBE sequence demonstrates superior image quality
      when evaluating the orbits as compared with conventional MPRAGE and 2D TSE
      sequences. ADVANCES IN KNOWLEDGE: Radial-VIBE employs unique non-Cartesian k
      space sampling in a radial or spoke-wheel fashion which provides superior image
      quality improving diagnostic capability in the evaluation of the orbits.

PMID- 26194590
TI  - Clinical application of surface projection in the localization of metal foreign
      bodies using computed tomography scan.
AB  - OBJECTIVE: To analyse the clinical efficacy of surface projection in the
      localization and removal of metal foreign bodies using CT scan. METHODS: Total
      795 cases with 1008 metal foreign bodies were treated at our hospital in 2012.
      Pre-operative surface projection was performed to localize foreign bodies in
      patients under the guidance of CT scan. The removal path from the skin surface to
      foreign body and puncture site were then determined. Finally, the foreign bodies
      were extracted using proper foreign body forceps which were chosen according to
      the size, depth and position of the foreign bodies in different parts of the
      human body. The incision length, operative time and intraoperative blood loss
      were recorded. Additionally, outpatient follow-up was scheduled post-operatively
      for 1 week. RESULTS: The accurate localization rate under the guidance of CT scan
      was 100%, and 1008 pieces of metal foreign bodies were all successfully removed
      with a removal rate of 100%. The mean incision length was 0.4 +/- 0.1 cm, the
      mean operative time was 4.1 +/- 2.0 min and the intraoperative blood loss was 1.1
      +/- 0.5 ml. These results showed minimal invasiveness, shorter operative time and
      minimal blood loss, respectively. Additionally, the results of outpatient follow
      up showed that the wound healed spontaneously. Moreover, there were no
      significant bleeding, incision infections or complications. CONCLUSION: Surface
      projection may be an accurate and effective method for the pre-operative
      localization and extraction of metal foreign bodies. ADVANCES IN KNOWLEDGE: (1)
      Surface projection was applied for localization of metal foreign bodies in our
      study. (2) The accurate localization rate of surface projection under the
      guidance of CT scan was 100%. (3) All foreign bodies were successfully removed
      with a removal rate of 100%. (4) Surface projection technique has advantages in
      the removal of foreign bodies.

PMID- 26194591
TI  - Risk and resiliency: thrombotic and ischemic vascular events, in cyanotic
      congenital heart disease.

PMID- 26194592
TI  - The Gordian knot of thromboembolism in congenital heart disease.

PMID- 26194593
TI  - Dosimetric Comparison and Evaluation of Three Radiotherapy Techniques for Use
      after Modified Radical Mastectomy for Locally Advanced Left-sided Breast Cancer.
AB  - This study aimed to compare the post-modified radical mastectomy radiotherapy
      (PMRMRT) for left-sided breast cancer utilizing 3-dimensional conformal
      radiotherapy with field-in-field technique (3DCRT-FinF), 5-field intensity
      modulated radiation therapy (5F-IMRT) and 2- partial arc volumetric modulated arc
      therapy (2P-VMAT). We created the 3 different PMRMRT plans for each of the ten
      consecutive patients. We performed Kruskal-Wallis analysis of variance (ANOVA)
      followed by the Dunn's-type multiple comparisons to establish a hierarchy in
      terms of plan quality and dosimetric benefits. P < 0.05 was considered
      statistically significant. Both 5F-IMRT and 2P-VMAT plans exhibited similar PTV
      coverage (V95%), hotspot areas (V110%) and conformity (all p > 0.05), and
      significantly higher PTV coverage compared with 3DCRT-FinF (both p < 0.001). In
      addition, 5F-IMRT plans provided significantly less heart and left lung radiation
      exposure than 2P-VMAT (all p < 0.05). The 3DCRT-FinF plans with accurately
      estimated CTV displacement exhibited enhanced target coverage but worse organs at
      risk (OARs) sparing compared with those plans with underestimated displacements.
      Our results indicate that 5F-IMRT has dosimetrical advantages compared with the
      other two techniques in PMRMRT for left-sided breast cancer given its optimal
      balance between PTV coverage and OAR sparing (especially heart sparing).
      Individually quantifying and minimizing CTV displacement can significantly
      improve dosage distribution.

PMID- 26194595
TI  - The Role of Clinical Registries in Monitoring Drug Safety and Efficacy.
AB  - The last 20 years has seen a rapid growth in the area of clinical registries to
      monitor the safety and quality of healthcare delivery across the globe. Clinical
      registries have predominantly focussed on tertiary care service delivery, often
      procedurally based and directed to identifying variation in patient outcomes.
      They are also often used to determine whether evidence-based therapeutic
      guidelines are being adopted and whether safety signals are being identified when
      novel therapies are first released into clinical practice. This paper will
      examine the role of clinical quality registries as a pharmacovigilance
      methodology for the 21st Century. 

PMID- 26194594
TI  - Effect of exercise training on neuromuscular function of elbow flexors and knee
      extensors of type 2 diabetic patients.
AB  - PURPOSE: The effects of exercise training on neuromuscular function of arm and
      leg muscles in type 2 diabetic patients (T2D) was investigated. METHODS: Eight
      T2D sedentary male patients (61.0+/-2.3years) and eight sedentary healthy age
      matched control subjects (H, 63.9+/-3.8years) underwent a 16-week supervised
      combined endurance and resistance exercise program. Before and after training,
      maximal isometric (MVIC), isokinetic (15, 30, 60, 120, 180, 240 degrees s(-1))
      torque and muscle endurance of the elbow flexors (EF) and knee extensors (KE)
      were assessed. Simultaneously, surface electromyographic signals from biceps
      brachii (BB) and vastus lateralis (VL) muscles were recorded and muscle fiber
      conduction velocity (MFCV) estimated. RESULTS: Following training, maximal torque
      of the KE increased during MVIC and isokinetic contractions at 15 and 30 degrees
      s(-1) in the T2D (+19.1+/-2.7% on average; p<0.05) but not in the H group (+7+/
      0.9%; p>0.05). MFCV recorded from the VL during MVIC and during isokinetic
      contractions at 15 and 30 degrees s(-1) increased (+11.2+/-1.6% on average;
      p<0.01), but in the diabetic group only. Muscular endurance was lower in T2D
      (20.1+/-0.7s) compared to H (26.9+/-1.3s), with an associated increase in the
      MFCV slope after training in the KE muscles only. CONCLUSION: The effect of a
      combined exercise training on muscle torque appears to be angular velocity
      specific in diabetic individuals, with a more pronounced effect on KE muscles and
      at slow contraction velocities, along with an associated increase in the MFCV.
      MFCV appears to be a more sensitive marker than torque in detecting the early
      signs of neuromuscular function reconditioning.

PMID- 26194596
TI  - Condition-specific Streaming versus an Acuity-based Model of Cardiovascular Care:
      A Historically-controlled Quality Improvement Study Evaluating the Association
      with Early Clinical Events.
AB  - BACKGROUND: Ensuring optimal evidence translation is challenging when health
      service design has not kept pace with developments in care. Differences in
      patient outcomes were evident when specific cardiac conditions were discordant
      with the subspecialty of the cardiologists managing their care. We prospectively
      explored the clinical and health service implications of a "condition-based"
      redesign in cardiac care delivery, rather than acuity-based, within a tertiary
      hospital. METHODS: Prospective evaluation of a disease-specific streaming model
      of care compared to propensity-matched historical controls, among cardiac
      patients admitted to a tertiary hospital cardiology unit was undertaken. The
      outcome measures of 30-day death, and readmission for myocardial infarction,
      cardiac arrhythmia, and heart failure were explored. RESULTS: In total, 2018
      patients admitted subsequent to the implementation of the streaming model were
      compared with 1830 patients admitted prior. The median age was 68.9 years, and
      39.5% were female. There was no significant difference in the overall proportion
      of patients admitted with an acute coronary syndrome, arrthythmia or heart
      failure, nor their Charlson index before and after streaming. Subsequent to the
      implementation, there was a reduction in the use of angiography (pre: 35.4% vs.
      post: 31.2%, p=0.007) and echocardiography (pre: 59.4% vs. post: 55.6%, p=0.007).
      A reduction in length of length-of-stay was observed in the entire cohort (pre:
      2.7 (range: 1.2-5.0) days vs. post: 2.3 (range 1.0-4.5) days, p=0.0003). By 30
      days, the propensity-adjusted hazard ratio for major adverse cardiac events and
      death or any cardiovascular admission was 0.76 (95% C.I. 0.59-0.97, p=0.026).
      CONCLUSION: Cardiac service redesign that streams cardiac patients by presenting
      diagnosis into teams designed to treat that condition may provide capacity and
      productivity gains for health services striving to improve outcome and
      efficiency.

PMID- 26194597
TI  - Successful Treatment of a Giant Left Atrial Mass Stemming from Pulmonary Vein
      after Chemotherapy-radiotherapy Combination in a Patient with Lung
      Adenocarcinoma.

PMID- 26194599
TI  - Efficacy of e-technologies in improving breastfeeding outcomes among perinatal
      women: a meta-analysis.
AB  - A growing line of research has highlighted that e-technologies may play a
      promising role in improving breastfeeding outcomes. The objective of this review
      was to synthesise the best of available evidence by conducting a meta-analysis to
      evaluate whether e-technologies have had any effect in improving breastfeeding
      outcomes among perinatal women. The review was conducted using nine electronic
      databases to search for English-language research studies from 2007 to 2014. A
      'risk of bias' table was used to assess methodological quality. Meta-analysis was
      performed with the RevMan software. The Q test and I(2) test was used to assess
      the heterogeneity. The test of overall effect was assessed using z-statistics at
      P < 0.05. Of 1842 studies identified through electronic searches and reference
      lists, 16 experimental studies were selected after applying the inclusion and
      exclusion criteria. Half of the selected studies had a low risk of bias, from
      which a total of 5505 women in six countries in these studies were included. Meta
      analyses revealed that e-technologies significantly improved exclusive
      breastfeeding initiation (z = 6.90, P < 0.00001), exclusive breastfeeding at 4
      weeks (z = 2.12, P = 0.03) and 6 months (z = 3.2, P = 0.001), breastfeeding
      attitude (z = 3.01, P = 0.003) and breastfeeding knowledge (z = 4.54, P = <
      0.00001) in subgroup analyses. This review provides support for the development
      of web-based, texting messaging, compact disc read-only memory, electronic
      prompts and interactive computer agent interventions for promoting and supporting
      breastfeeding.

PMID- 26194600
TI  - Coexistence of Malakoplakia and Papillary Urothelial Carcinoma of the Urinary
      Bladder.
AB  - Malakoplakia is a rare granulomatous disease that commonly involves the
      genitourinary tract, with the urinary bladder being the most frequently affected
      site. Grossly, malakoplakia can present as soft yellow plaques, nodules, bladder
      mass, or even without any visible lesion. In this article, we present a 74-year
      old female with a background of hypertension, hyperlipidemia, and poorly
      controlled diabetes who presented with sepsis of unknown origin. During the
      course of the investigation of the source of her sepsis, an incidental bladder
      tumor was discovered. She subsequently underwent transurethral resection of the
      bladder tumor. Histology revealed ordinary low-grade papillary urothelial
      carcinoma that had small colonies of malakoplakia that appeared to have developed
      secondary to the tumor and presented concurrently. We seek to demonstrate the
      rare association of papillary urothelial carcinoma and malakoplakia. 

PMID- 26194601
TI  - Thymic Tumor With Adenoid Cystic Carcinoma-Like Features: A Study of a Clinically
      Favorable Case Followed for 9 Years.
AB  - Thymic tumors with adenoid cystic carcinoma-like features are true rarities, with
      only 6 cases reported. Our knowledge of their clinical behavior is insufficient.
      We present a case of a noninvasive cribriform tumor that was followed, including
      a 4-year period after tumor resection and radiation therapy, for a total of 9
      years. The tumor was purely epithelial. It was positive for keratins (AE-1/AE-3,
      CK19, 34betaE12,CK5/6), MOC-31, P63, P40, CD10, and MYB, and was negative for
      myoepithelial or neuroendocrine markers. Presence of cell processes, desmosome
      like junctions with tonofilaments and multifocally reduplicated basal lamina was
      noted on ultrastructural examination. Two signals of the MYB gene per cell were
      detected by fluorescence in situ hybridization. No monosomy or translocations of
      the gene were found. Although additional clinical studies are necessary, it seems
      that indolent behavior of cribriform noninvasive subset of these tumors may be
      anticipated. 

PMID- 26194598
TI  - Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth
      Cohort.
AB  - BACKGROUND: Evidence from animal and human studies indicates that thyroid hormone
      deficiency during early gestation alters brain development. As schizophrenia is
      associated with prenatal brain insults and premorbid cognitive deficits, we
      tested the a priori hypothesis that serologically defined maternal thyroid
      deficiency during early gestation to mid-gestation is associated with
      schizophrenia in offspring. METHODS: The investigation is based on the Finnish
      Prenatal Study of Schizophrenia, a nested case-control study that included
      archived maternal sera from virtually all pregnancies since 1983 (N = >1
      million). We identified all offspring in the cohort with a diagnosis of
      schizophrenia based on the national inpatient and outpatient register and matched
      them on sex, date of birth, and residence in Finland at time of onset of the case
      to comparison subjects (1:1) from the cohort. Maternal sera of 1010 case-control
      pairs were assessed for free thyroxine, and sera of 948 case-control pairs were
      assessed for thyroid-stimulating hormone. RESULTS: Maternal hypothyroxinemia
      (free thyroxine <=10th percentile, normal thyroid-stimulating hormone) was
      associated with an increased odds of schizophrenia (odds ratio = 1.75, 95%
      confidence interval = 1.22-2.50, p = .002). When adjusted for maternal
      psychiatric history, province of birth, and maternal smoking during pregnancy,
      the association remained significant (odds ratio = 1.70, 95% confidence interval
      = 1.13-2.55, p = .010). CONCLUSIONS: In a large, national birth cohort,
      prospectively documented hypothyroxinemia during early gestation to mid-gestation
      was associated with increased odds of schizophrenia in offspring. This
      information can inform translational studies of maternal hypothyroxinemia
      examining molecular and cellular deviations relevant to schizophrenia.

PMID- 26194602
TI  - Serum fibrosis biomarkers predict death and graft loss in liver transplantation
      recipients.
AB  - Noninvasive serum fibrosis biomarkers predict clinical outcomes in pretransplant
      patients with chronic liver disease. We investigated the role of serum fibrosis
      biomarkers and of changes in biomarkers in predicting death and graft loss after
      liver transplantation (LT). We included 547 patients who underwent LT between
      1991 and 2012 and who met the following criteria: patient and graft survival > 12
      months; serum fibrosis biomarkers aspartate aminotransferase-to-platelet ratio
      index (APRI), fibrosis score 4 (FIB-4), and nonalcoholic fatty liver disease
      (NAFLD) fibrosis score available at 1 year after LT; and a minimum follow-up of 1
      year. Delta of fibrosis biomarkers was defined as (end of follow-up score-
      baseline score)/follow-up duration. Baseline and delta fibrosis biomarkers were
      associated with death: APRI > 1.5 (adjusted hazard ratio [aHR], 2.2; 95%
      confidence interval [CI], 1.4-3.3; P < 0.001) and delta APRI > 0.5 (aHR, 5.3; 95%
      CI, 3.4-8.2; P < 0.001); FIB-4 > 3.3 (aHR, 1.9; 95% CI, 1.3-2.8; P = 0.002) and
      delta FIB-4 > 1.4 (aHR, 2.4; 95% CI, 1.4-4.1; P = 0.001); and NAFLD fibrosis
      score > 0.7 (aHR, 1.9; 95% CI, 1.3-2.9; P = 0.002) and delta NAFLD fibrosis score
      (aHR, 3.7; 95% CI, 2.6-5.4; P < 0.001). Baseline and delta fibrosis biomarkers
      were associated also with graft loss. In conclusion, serum fibrosis biomarkers 1
      year after LT and changes in serum fibrosis biomarkers predict death and graft
      loss in LT recipients. They may help in risk stratification of LT recipients and
      identify patients requiring closer monitoring.

PMID- 26194604
TI  - Assessing satisfaction in men with premature ejaculation after dapoxetine
      treatment in real-world practice.
AB  - INTRODUCTION: There are limited data on the treatment satisfaction with
      dapoxetine in patients with premature ejaculation (PE). AIMS: We aimed to
      evaluate the treatment satisfaction, effectiveness and safety of dapoxetine for
      PE patients. METHODS: Subjects received dapoxetine (30 mg or 60 mg) alone or in
      combination with a phosphodiesterase type 5 inhibitor, if concurrent with
      erectile dysfunction for more than 4 weeks in clinical practice. Main outcome
      measures include Clinical Global Impression of Change (CGIC) and Clinical Global
      Impression of Satisfaction (CGIS). RESULTS: From March 2014 to January 2015, a
      total of 286 PE patients received dapoxetine treatment in this study, with 137
      (47.9%) patients diagnosed with lifelong PE and 149 (52.1%) patients diagnosed
      with acquired PE. At the final follow-up visit, the mean intravaginal ejaculatory
      latency time (an increase of 3.4 min) and mean score of Premature Ejaculation
      Diagnostic Tool (a decrease of -5.0) improved significantly from baseline, and
      the satisfaction rate and response rate to dapoxetine treatment were 45.0% and
      74.6%, respectively. Satisfaction with dapoxetine treatment was highly correlated
      with treatment response, and might be improved by scheduled follow-up visits and
      escalation to a higher dose. Subjects with diabetes mellitus (DM) reported a
      lower treatment response than those without DM. Treatment-emergent adverse event
      (TEAEs) occurred in 47.7% of patients, but no serious TEAEs were reported.
      CONCLUSION: Our real-world data highlight the effectiveness of dapoxetine and the
      importance of follow-up visits for the treatment of PE. Half of PE patients were
      not satisfied with dapoxetine treatment, which reflects an unmet need of present
      approach or an unrealistic expectation from PE patients.

PMID- 26194603
TI  - Psychological Distress Among School-Aged Children with and Without Intrauterine
      Cocaine Exposure: Perinatal Versus Contextual Effects.
AB  - Whether intrauterine cocaine exposure (IUCE) explains unique variance in
      psychiatric functioning among school age children, even after controlling for
      other biological and social risk factors, has not been fully delineated. As part
      of a longitudinal birth cohort study of children with and without IUCE, we
      conducted and analyzed data based on structured clinical interviews with 105
      children (57% male) and their caregivers when the child was approximately 8.5
      years old; 47% of the children had experienced IUCE. Interviews included past and
      current major psychological disorders and sub-threshold mental health symptoms.
      Potential covariates were ascertained by interviews of birth mothers and other
      caregivers from shortly after the child's birth until the 8.5-year visit. More
      than one-third of children met DSM-IV criteria for one or more mood, anxiety,
      attention deficit, or disruptive behavior disorders. IUCE was not significantly
      associated with children's history of psychological distress, in either bivariate
      or multiple logistic regressions. In contrast, birth mothers' acknowledgement of
      greater psychiatric distress at baseline and higher levels of alcohol consumption
      during pregnancy, and at 8.5 years caregivers' reports of their own psychological
      distress, and children's lower IQ were predictors of higher rates of
      psychological morbidity. Findings are consistent with prior reports suggesting
      that, regardless of IUCE status, children from low-income, urban backgrounds are
      at heightened risk for psychological distress. Results underscore the need for
      closer monitoring of the mental health of children living in low-income
      households, with or without intrauterine substance exposures, to facilitate
      access to appropriate services.

PMID- 26194605
TI  - Analysis of the equine ovarian structure during the first twelve months of life
      by three-dimensional internal structure microscopy.
AB  - A three-dimensional internal structure microscopy (3D-ISM) can clarify the
      anatomical arrangement of internal structures of equine ovaries. In this study,
      morphological changes of the equine ovary over the first 12 months of life were
      investigated by 3D-ISM in 59 fillies and by histological analysis in 2 fillies.
      The weight and volume of the paired ovaries initially decreased from 0 to 1
      months to 2 to 3 months of age and then significantly increased at 8 to 12 months
      of age. The ovulation fossa was first observed around the 3rd month and became
      evident after the 6th month. The number of follicles with a diameter of >=10 mm
      and the diameter of the largest follicle increased gradually after 6 months of
      age. On a volume basis, the medulla accounted for nearly 90% of the whole ovary
      at 0 to 1 months of age, but significantly decreased from 2 to 3 months of age.
      The volume of the cortex increased progressively after birth and reached
      approximately 60% of the total volume at 8 to 12 months of age. This significant
      development of the cortex coincided with the increased number and size of large
      follicles observed from 6 months of age. These results suggest that the
      development of the cortex plays a role in the maturation of the follicles and the
      equine ovary undergoes substantial morphological changes postnatally until
      puberty. 

PMID- 26194606
TI  - Ontogenic and morphological study of gonadal formation in genetically-modified
      sex reversal XY(POS) mice.
AB  - Mammalian sexual fate is determined by the presence or absence of sex determining
      region of the Y chromosome (Sry) in the "bipotential" gonads. Recent studies have
      demonstrated that both male and female sexual development are induced by distinct
      and active genetic pathways. Breeding the Y chromosome from Mus m. domesticus
      poschiavinus (POS) strains into C57BL/6J (B6J) mice (B6J-XY(POS)) has been shown
      to induce sex reversal (75%: bilateral ovary, 25%: true hermaphrodites). However,
      our B6N-XY(POS) mice, which were generated by backcrossing of B6J-XY(POS) on an
      inbred B6N-XX, develop as males (36%: bilateral testis with fertility as well as
      bilateral ovary (34%), and the remainder develop as true hermaphrodites. Here, we
      investigated in detail the expressions of essential sex-related genes and
      histological features in B6N-XY(POS) mice from the fetal period to adulthood. The
      onsets of both Sry and SRY-box 9 (Sox9) expressions as determined
      spatiotemporally by whole-mount immunohistochemistry in the B6N-XY(POS) gonads
      occurred 2-3 tail somites later than those in B6N-XY(B6) gonads, but earlier than
      those in B6J-XY(POS), respectively. It is possible that such a small difference
      in timing of the Sry expression underlies testicular development in our B6N
      XY(POS). Our study is the first to histologically show the expression and ectopic
      localization of a female-related gene in the XY(POS) testes and a male-related
      gene in the XY(POS) ovaries. The results from these and previous experiments
      indicate that the interplay between genome variants, epigenetics and
      developmental gene regulation is crucial for testis development. 

PMID- 26194607
TI  - A preprocedural checklist improves the safety of emergency department intubation
      of trauma patients.
AB  - OBJECTIVES: Endotracheal intubation of trauma patients is a vital and high-risk
      procedure in the emergency department (ED). The hypothesis was that
      implementation of a standardized, preprocedural checklist would improve the
      safety of this procedure. METHODS: A preprocedural intubation checklist was
      developed and then implemented in a prospective pre-/postinterventional study in
      an academic trauma center ED. The proportions of trauma patients older than 16
      years who experienced intubation-related complications during the 6 months before
      checklist implementation and 6 months after implementation were compared.
      Intubation-related complications included oxygen desaturation, emesis, esophageal
      intubation, hypotension, and cardiac arrest. Additional outcomes included time
      from paralysis to intubation and adherence to safety process measures. RESULTS:
      During the study, 141 trauma patients were intubated, including 76 in the
      prechecklist period and 65 in the postchecklist period. A lower proportion of
      patients experienced intubation-related complications in the postchecklist period
      (1.5%) than the prechecklist period (9.2%), representing a 7.7% (95% confidence
      interval = 0.5% to 14.8%) absolute risk reduction. Paralysis-to-intubation time
      was also lower in the postchecklist period (median = 82 seconds, interquartile
      range [IQR] = 68 to 101 seconds) compared to the prechecklist period (median = 94
      seconds, IQR = 78 to 115 seconds; p = 0.02). Adherence to safety process measures
      also improved, with all safety measures performed in 69.2% in the postchecklist
      period compared to 17.1% before the checklist (p < 0.01). CONCLUSIONS:
      Implementation of a preintubation checklist for ED intubation of trauma patients
      was associated with a reduction in intubation-related complications, decreased
      paralysis-to-intubation time, and improved adherence to recognized safety
      measures.

PMID- 26194608
TI  - Xanthohumol impairs glucose uptake by a human first-trimester extravillous
      trophoblast cell line (HTR-8/SVneo cells) and impacts the process of
      placentation.
AB  - In this study, we aimed to investigate modulation of glucose uptake by the HTR
      8/SVneo human first-trimester extravillous trophoblast cell line by a series of
      compounds and to study its consequences upon cell proliferation, viability and
      migration. We observed that uptake of (3)H-deoxy-d-glucose ((3)H-DG; 10 nM) was
      time-dependent, saturable, inhibited by cytochalasin B (50 and 100 uM), phloretin
      (0.5 mM) and phloridzin (1 mM), insulin-insensitive and sodium-independent. In
      the short term (30 min), neither 5-HT (100-1000 uM), melatonin (10 nM) nor the
      drugs of abuse ethanol (100 mM), nicotine (100 uM), cocaine (25 uM), amphetamine
      (10-25 uM) and 3,4-methylenedioxy-N-methamphetamine (10 uM) affected (3)H-DG
      uptake, while dexamethasone (100-1000 uM), fluoxetine (100-300 uM), quercetin,
      epigallocatechin-3-gallate (30-1000 uM), xanthohumol (XH) and resveratrol (1-500
      uM) decreased it. XH was the most potent inhibitor [IC50 = 3.55 (1.37-9.20) uM]
      of (3)H-DG uptake, behaving as a non-competitive inhibitor of (3)H-DG uptake,
      both after short- and long-term (24 h) treatment. The effect of XH (5 uM; 24 h)
      upon (3)H-DG uptake involved mammalian target of rapamycin, tyrosine kinases and
      c-Jun N-terminal kinases intracellular pathways. Moreover, XH appeared to
      decrease cellular uptake of lactate due to inhibition of the monocarboxylate
      transporter 1. Additionally, XH (24 h; 5 uM) decreased cell viability,
      proliferation, culture growth and migration. The effects of XH upon cell
      viability and culture growth, but not the antimigratory effect, were mimicked by
      low extracellular glucose conditions and reversed by high extracellular glucose
      conditions. We thus suggest that XH, by inhibiting glucose cellular uptake and
      impairing HTR-8/SVneo cell viability and proliferation, may have a deleterious
      impact in the process of placentation. 

PMID- 26194609
TI  - Clinical and radiological cervical spine evaluation in retired professional rugby
      players.
AB  - OBJECT Acute cervical spine injuries have been extensively studied in high-level
      contact sports. However, the relation between the appearance of degenerative
      cervical spine disease and the exposure to repeated trauma in such sports as
      rugby is still unclear. Using clinical and MRI evaluation, we aimed to determine
      if former professional rugby players had more serious degenerative cervical spine
      symptoms than the general population. METHODS Two groups, one composed of 101
      former rugby players (all men, mean age 40.3 years, range 35-47 years, SD 2.3
      years) and the other of 85 male volunteers serving as a control group (mean age
      41.6 years, range 35-49 years, SD 4.5 years) were studied. The former rugby
      players were evaluated on average 5.8 years after retirement (range 1-16 years,
      SD 3.5 years). The groups were matched in terms of sex, age, job, current sports
      training, and smoking habits. Each participant received a complete neurological
      evaluation. Clinical symptoms were evaluated using the Japanese Orthopaedic
      Association (JOA) questionnaire, and chronic neck pain was specifically evaluated
      using a visual analog scale (VAS) and the Neck Disability Index (NDI). Overall,
      25 MRI studies were performed in each group. MRI studies, including dynamic
      sequences, focused on degenerative lesions (Matsumoto score and canal diameter)
      and on muscular and medullary morphological analysis. RESULTS Significantly more
      former rugby players than controls complained of chronic neck pain (51 [50.50%]
      of 101 vs 27 [31.76%] of 85, p = 0.01). Rugby players also had significant
      reductions of neck mobility. Nevertheless, in those complaining of pain, there
      was no statistically significant difference between groups with respect to VAS
      and NDI scores (p = 0.57). On MRI, former rugby players had a narrower vertebral
      canal (on average 0.88 +/- 0.167 cm vs 0.99 +/- 0.130 cm, p = 0.007) and more
      foraminal stenosis (p = 0.01). No significant difference in the Matsumoto score
      was found between the 2 groups with respect to other degenerative lesions. Former
      rugby players had more often undergone surgery for a degenerative condition than
      had members of the control group (10 cases vs 0 in the control group, p =
      0.0021). CONCLUSIONS A few years after retirement, former professional rugby
      players seem to have more frequent cervical spine pain and MRI degenerative
      lesions, such as foraminal stenosis and narrowing of the spinal canal, compared
      with controls who had not been professional rugby players. A longer evaluation is
      necessary to determine if these findings persist over time.

PMID- 26194611
TI  - Higher interleukin 21 level is predictive of relapse in immune thrombocytopenia.
      Is it associated with activation of the complement system?

PMID- 26194613
TI  - The genetics of celiac disease: A comprehensive review of clinical implications.
AB  - Celiac disease (CD) is a complex immune-related disease with a very strong
      genetic component. Multiple genetic findings over the last decade have added to
      the already known MHC influence numerous genetic variants associated to CD
      susceptibility. Currently, it is well-established that 6 MHC and 39 non-MHC loci,
      including a higher number of independent genetic variants, are associated to
      disease risk. Moreover, additional regions have been recently implicated in the
      disease, which would increase the number of involved loci. Together, the firmly
      described genetic variants account for roughly 31% of CD heritability, being 25%
      explained by the MHC influence. These new variants represent markers of disease
      risk and turn the identification of the causal genes and the causal variants
      inside the associated loci, as well as their precise biological role on the
      disease, into a major challenge in CD research. Numerous studies have been
      developed with this aim showing the high impact of risk variants on gene
      expression. These studies also indicate a central role of CD4(+) T cells in CD
      pathogenesis and point to B cells as important players, which is in accordance
      with the key steps highlighted by the immunological models of pathogenesis. We
      comprehensively summarize the current knowledge about the genetic architecture of
      CD, characterized by multiple low-risk variants located within diverse loci which
      are most likely affecting genes with immune-related functions. These findings are
      leading to a better understanding of CD pathogenesis and helping in the design of
      new treatments. The repertoire of potential drug targets for CD has largely
      broadened last years, bringing us closer to get alternative or complementary
      treatments to the life-long gluten-free diet, the only effective treatment so
      far. Epigenetics and microbiota are emerging as potent factors modulating disease
      risk and putatively affecting disease manifestation, which are also being
      explored as therapeutic targets.

PMID- 26194612
TI  - PHI and PCA3 improve the prognostic performance of PRIAS and Epstein criteria in
      predicting insignificant prostate cancer in men eligible for active surveillance.
AB  - PURPOSE: To assess the performance of prostate health index (PHI) and prostate
      cancer antigen 3 (PCA3) when added to the PRIAS or Epstein criteria in predicting
      the presence of pathologically insignificant prostate cancer (IPCa) in patients
      who underwent radical prostatectomy (RP) but eligible for active surveillance
      (AS). METHODS: An observational retrospective study was performed in 188 PCa
      patients treated with laparoscopic or robot-assisted RP but eligible for AS
      according to Epstein or PRIAS criteria. Blood and urinary specimens were
      collected before initial prostate biopsy for PHI and PCA3 measurements.
      Multivariate logistic regression analyses and decision curve analysis were
      carried out to identify predictors of IPCa using the updated ERSPC definition.
      RESULTS: At the multivariate analyses, the inclusion of both PCA3 and PHI
      significantly increased the accuracy of the Epstein multivariate model in
      predicting IPCa with an increase of 17 % (AUC = 0.77) and of 32 % (AUC = 0.92),
      respectively. The inclusion of both PCA3 and PHI also increased the predictive
      accuracy of the PRIAS multivariate model with an increase of 29 % (AUC = 0.87)
      and of 39 % (AUC = 0.97), respectively. DCA revealed that the multivariable
      models with the addition of PHI or PCA3 showed a greater net benefit and
      performed better than the reference models. In a direct comparison, PHI
      outperformed PCA3 performance resulting in higher net benefit. CONCLUSIONS: In a
      same cohort of patients eligible for AS, the addition of PHI and PCA3 to Epstein
      or PRIAS models improved their prognostic performance. PHI resulted in greater
      net benefit in predicting IPCa compared to PCA3.

PMID- 26194614
TI  - GSK3beta Interactions with Amyloid Genes: An Autopsy Verification and Extension.
AB  - Glyocogen synthase kinase 3 (GSK3) plays an important role in the pathophysiology
      of Alzheimer's disease (AD) through the phosphorylation of tau. Recent work has
      suggested that GSK3beta also plays a role in the amyloid pathway of AD through
      genetic interactions with APP and APBB2 on in vivo measures of amyloid. This
      project extends the previously identified genotype interactions to an autopsy
      measure of amyloid, while also testing the same interactions leveraging gene
      expression data quantified in the prefrontal cortex. 797 participants (251
      cognitively normal, 196 mild cognitive impairment, and 350 Alzheimer's disease)
      were drawn from the Religious Orders Study and Rush Memory and Aging Project. A
      mean score of amyloid load was calculated across eight brain regions, gene
      expression levels from frozen sections of the dorsolateral prefrontal cortex were
      quantified using RNA amplification, and expression signals were generated using
      Beadstudio. Three SNPs previously identified in genetic interactions were
      genotyped using the Illumina 1M genotyping chip. Covariates included age, sex,
      education, and diagnosis. We were able to evaluate 2 of the 3 previously
      identified interactions, of which the interaction between GSK3beta (rs334543) and
      APBB2 (rs2585590) was found in this autopsy sample (p = 0.04). We observed a
      comparable interaction between GSK3beta and APBB2 when comparing the highest
      tertile of gene expression to the lowest tertile, t(1) = -2.03, p = 0.043. These
      results provide additional evidence of a genetic interaction between GSK3beta and
      APBB2 and further suggest that GSK3beta is involved in the pathophysiology of
      both of the primary neuropathologies of Alzheimer's disease.

PMID- 26194615
TI  - Cognitive Impairment After Sleep Deprivation Rescued by Transcranial Magnetic
      Stimulation Application in Octodon degus.
AB  - Sleep is indispensable for maintaining regular daily life activities and is of
      fundamental physiological importance for cognitive performance. Sleep deprivation
      (SD) may affect learning capacity and the ability to form new memories,
      particularly with regard to hippocampus-dependent tasks. Transcranial magnetic
      stimulation (TMS) is a non-invasive procedure of electromagnetic induction that
      generates electric currents, activating nearby nerve cells in the stimulated
      cortical area. Several studies have looked into the potential therapeutic use of
      TMS. The present study was designed to evaluate how TMS could improve learning
      and memory functions following SD in Octodon degus. Thirty juvenile (18 months
      old) females were divided into three groups (control, acute, and chronic TMS
      treatment-with and without SD). TMS-treated groups were placed in plastic
      cylindrical cages designed to keep them immobile, while receiving head magnetic
      stimulation. SD was achieved by gently handling the animals to keep them awake
      during the night. Behavioral tests included radial arm maze (RAM), Barnes maze
      (BM), and novel object recognition. When TMS treatment was applied over several
      days, there was significant improvement of cognitive performance after SD, with
      no side effects. A single TMS session reduced the number of errors for the RAM
      test and improved latency and reduced errors for the BM test, which both evaluate
      spatial memory. Moreover, chronic TMS treatment brings about a significant
      improvement in both spatial and working memories.

PMID- 26194616
TI  - The Addiction-Related Gene Ankk1 is Oppositely Regulated by D1R- and D2R-Like
      Dopamine Receptors.
AB  - The ankyrin repeat and kinase domain containing 1 (ANKK1) TaqIA polymorphism has
      been extensively studied as a marker of the gene for dopamine receptor D2 (DRD2)
      in addictions and other dopamine-associated traits. In vitro mRNA and protein
      studies have shown a potential connection between ANKK1 and the dopaminergic
      system functioning. Here, we have investigated whether Ankk1 expression in the
      brain is regulated by treatment with dopaminergic agonists. We used quantitative
      RT-PCR of total brain and Western blots of specific brain areas to study Ankk1 in
      murine brain after dopaminergic treatments. We found that Ankk1 mRNA was
      upregulated after activation of D1R-like dopamine receptors with SKF38393 (2.660
      +/- 1.035-fold; t: 4.066, df: 11, P = 0.002) and apomorphine (2.043 +/- 0.595
      fold; t: 3.782, df: 8, P = 0.005). The D2R-like agonist quinelorane has no effect
      upon Ankk1 mRNA (1.004 +/- 0.580-fold; t: 0.015, df: 10, P = 0.9885). In
      contrast, mice treatment with the D2R-like agonists 7-OH-DPAT and aripiprazole
      caused a significant Ankk1 mRNA downregulation (0.606 +/- 0.057-fold; t: 2.786,
      df: 10, P = 0.02 and 0.588 +/- 0.130-fold; t: 2.394, df: 11, P = 0.036,
      respectively). With respect the Ankk1 proteins profile, no effects were found
      after SKF38393 (t: 0.54, df: 2, P = 0.643) and Quinelorane (t: 0.286, df: 8, P =
      0.782) treatments. In contrast, the D2R-like agonist 7-OH-DPAT (+/-) caused a
      significant increment of Ankk1 in the striatum (t: 2.718, df: 7; P = 0.03) when
      compared to the prefrontal cortex. The activation of D1R-like and D2-R-like leads
      to opposite transcriptional regulation of Ankk1 by specific pathways. 

PMID- 26194617
TI  - Failure of Neuroprotection Despite Microglial Suppression by Delayed-Start
      Myeloperoxidase Inhibition in a Model of Advanced Multiple System Atrophy:
      Clinical Implications.
AB  - Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease.
      Post-mortem hallmarks of MSA neuropathology include oligodendroglial alpha
      synuclein (alphaSYN) inclusions, striatonigral degeneration, olivopontocerebellar
      atrophy, and increased microglial activation that accompanies the wide spread
      neurodegeneration. Recently, we demonstrated upregulation of myeloperoxidase
      (MPO) in activated microglia and provided evidence for the role of microglial MPO
      in the mediation of MSA-like neurodegeneration (Stefanova et al. Neurotox Res
      21:393-404, 2015). The aim of the current study was to assess the therapeutic
      potency of MPO inhibition (MPOi) in a model of advanced MSA. We replicated the
      advanced pathology of MSA by intoxicating transgenic PLP-alpha-synuclein
      transgenic mice with 3-nitropropionic acid (3NP). After onset of the full-blown
      pathology, MSA mice received either MPOi or vehicle over 3 weeks. Motor phenotype
      and neuropathology were analyzed to assess the therapeutic efficacy of MPOi
      compared to vehicle treatment in MSA mice. MPOi therapy initiated after the onset
      of severe MSA-like neuropathology in mice failed to attenuate motor impairments
      and neuronal loss within the striatum, substantia nigra pars compacta, inferior
      olives, pontine nuclei, and cerebellar cortex. However, we observed a significant
      reduction of microglial activation in degenerating brain areas. Further, nitrated
      alphaSYN accumulation was reduced in the striatonigral region. In summary,
      delayed-start MPOi treatment reduced microglial activation and levels of nitrated
      alphaSYN in a mouse model of advanced MSA. These effects failed to impact on
      motor impairments and neuronal loss in contrast to previously reported disease
      modifying efficacy of early-start therapy with MPOi in MSA.

PMID- 26194618
TI  - Mango polyphenolics suppressed tumor growth in breast cancer xenografts in mice:
      role of the PI3K/AKT pathway and associated microRNAs.
AB  - The cytotoxic and anti-inflammatory properties of mango polyphenolics including
      gallic acid and gallotannins have been demonstrated in numerous types of cancers.
      We hypothesized that the phosphoinositide 3-kinase (PI3K)/AKT pathway and the
      expression of related miRNAs are involved in the chemotherapeutic activities of
      mango polyphenolics in a mouse xenograft model for breast cancer. The objectives
      of this research were to determine the tumor-cytotoxic activities of mango
      polyphenolics and the underlying molecular mechanisms involving
      posttranscriptional targets in BT474 breast cancer cells and xenografts in mice.
      In vitro findings showed cytotoxic effects of mango polyphenolics in BT474 breast
      cancer cells within a concentration range of 2.5 to 20 mg/L gallic acid
      equivalents. Mango polyphenolics suppressed the expression of PI3K, AKT, hypoxia
      inducible factor-1alpha, and vascular endothelial growth factor (VEGF) mRNA, and
      pAKT, AKT, pPI3K (p85), VEGF and nuclear factor-kappa B protein levels. The
      involvement of miR-126 was verified by using antagomiR for miR-126, where mango
      reversed the effect of the antagomiR of miR-126. In vivo, the intake of mango
      polyphenolics decreased the tumor volume by 73% in BT474 xenograft-bearing mice
      compared with the control group. In addition, mango reduced the expression of
      nuclear factor-kappa B (p65), pAKT, pPI3K, mammalian target of rapamycin, hypoxia
      inducible factor-1alpha, and VEGF protein in athymic nude mice. A screening for
      miRNA expression changes confirmed that mango polyphenolics modulated the
      expression of cancer-associated miRNAs including miR-126 in the xenografted
      tumors. In summary, mango polyphenolics have a chemotherapeutic potential against
      breast cancer that at least in part is mediated through the PI3K/AKT pathway and
      miR-126. 

PMID- 26194619
TI  - Loss of neprilysin alters protein expression in the brain of Alzheimer's disease
      model mice.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease displaying extracellular
      plaques formed by the neurotoxic amyloid beta-peptide (Abeta), and intracellular
      neurofibrillary tangles consisting of protein tau. However, how these pathologies
      relate to the massive neuronal death that occurs in AD brains remain elusive.
      Neprilysin is the major Abeta-degrading enzyme and a lack thereof increases Abeta
      levels in the brain twofold. To identify altered protein expression levels
      induced by increased Abeta levels, we performed a proteomic analysis of the brain
      of the AD mouse model APPsw and compared it to that of APPsw mice lacking
      neprilysin. To this end we established an LC-MS/MS method to analyze brain
      homogenate, using an (18) O-labeled internal standard to accurately quantify the
      protein levels. To distinguish between alterations in protein levels caused by
      increased Abeta levels and those induced by neprilysin deficiency independently
      of Abeta, the brain proteome of neprilysin deficient APPsw mice was also compared
      to that of neprilysin deficient mice. By this approach we identified
      approximately 600 proteins and the levels of 300 of these were quantified.
      Pathway analysis showed that many of the proteins with altered expression were
      involved in neurological disorders, and that tau, presenilin and APP were key
      regulators in the identified networks. The data have been deposited to the
      ProteomeXchange Consortium with identifiers PXD000968 and PXD001786
      (http://proteomecentral.proteomexchange.org/dataset/PXD000968 and
      (http://proteomecentral.proteomexchange.org/dataset/PXD001786). Interestingly,
      the levels of several proteins, including some not previously reported to be
      linked to AD, were associated with increased Abeta levels.

PMID- 26194620
TI  - Brilliant glyconanocapsules for trapping of bacteria.
AB  - Nanoprecipitation of miglyol into droplets surrounded by a functional
      glycopolymer generates nanocapsules of biointerest. Fluorophores are trapped in
      situ or post-grafted onto the crosslinked polymer shell for efficient imaging.
      The resulting colloids induce aggregation of bacteria through strong specific
      interactions and promote their facile removal. 

PMID- 26194622
TI  - Coupling effect between the structure and surface characteristics of electrospun
      carbon nanofibres on the electrochemical activity towards the VO2(+)/VO(2+) redox
      couple.
AB  - In order to investigate the structure-function relationship of electrospun carbon
      nanofibres (ECNFs), polyacrylonitrile (PAN)-based electrospun carbon webs (ECWs)
      have been developed, consisting of ECNFs carbonized over the temperature range of
      1000-1500  degrees C in a nitrogen atmosphere. The surface morphology,
      microstructure, composition, electrical conductivity and hydrophilicity of the
      ECNFs have been characterized. The electrochemical activity of the ECNFs towards
      the VO2(+)/VO(2+) redox reaction has been measured by cyclic voltammetry (CV) and
      electrochemical impedance spectroscopy (EIS). It is worth noting that the
      electrochemical performance of the ECNFs decreases firstly and then rises
      gradually with the increase in carbonization temperature, and a carbonization
      temperature of about 1300  degrees C is the turning point. This unusual
      phenomenon might be attributed to the coupling effect between the surface and
      structure characteristics of the ECNFs towards the VO2(+)/VO(2+) redox couple.
      The surface composition plays a leading role in the electrochemical activity of
      ECNFs carbonized over the temperature range of 1000-1300  degrees C; however, the
      edge planes of graphite crystallites which form during the high temperature range
      from 1300-1500  degrees C then become the dominant factor. Therefore, the
      electrochemical activity decreases with the reduction of functional groups on the
      surface from carbonization at 1000-1300  degrees C, and then increases with the
      addition of the edge planes of graphite crystallites from carbonization at 1300
      1500  degrees C. 

PMID- 26194621
TI  - Alpha male replacements and delayed dispersal in crested macaques (Macaca nigra).
AB  - In species with a high male reproductive skew, competition between males for the
      top dominant position is high and escalated fights are common between
      competitors. As a consequence, challenges incur potentially high costs. Selection
      should favor males who time an alpha male challenge to maximize chances of a
      successful outcome minimizing costs. Despite the importance of alpha male
      replacements for individual males, we know little about the timing of challenges
      and the condition of the challenger. We investigated the timing and process of
      alpha male replacements in a species living in multi-male groups with high male
      reproductive skew, the crested macaque. We studied four wild groups over 6 years
      in the Tangkoko Reserve, North Sulawesi, Indonesia, during which 16 alpha male
      replacements occurred. Although unusual for cercopithecines, male crested
      macaques delayed their natal dispersal until they attained maximum body mass and
      therefore fighting ability whereupon they emigrated and challenged the alpha male
      in another group. Accordingly, all observed alpha male replacements were from
      outside males. Ours is the first report of such a pattern in a primate species
      living in multi-male groups. Although the majority of alpha male replacements
      occurred through direct male-male challenges, many also took place
      opportunistically (i.e., after the alpha male had already been injured or had
      left the group). Furthermore, alpha male tenures were very short (averaging ca.
      12 months). We hypothesize that this unusual pattern of alpha male replacements
      in crested macaques is related to the species-specific combination of high male
      reproductive skew with a large number of males per group. Am. J. Primatol.
      79:e22448, 2017. (c) 2015 The Authors. American Journal of Primatology Published
      by Wiley Periodicals, Inc.

PMID- 26194623
TI  - Severe early onset ethylmalonic encephalopathy with West syndrome.
AB  - Ethylmalonic encephalopathy (EE) is a rare autosomal recessive disorder
      characterized by early onset encephalopathy, chronic diarrhoea, petechiae,
      orthostatic acrocyanosis and defective cytochrome c oxidase (COX) in muscle and
      brain. High levels of lactic, ethylmalonic and methylsuccinic acids are detected
      in body fluids. EE is caused by mutations in ETHE1 gene, a mitochondrial sulfur
      dioxygenase. Neurologic signs and symptoms include progressively delayed
      development, hypotonia, seizures, and abnormal movements. We report on the
      clinical, electroencephalographic and MRI findings of a baby with a severe early
      onset encephalopathy associated with novel ETHE1 gene mutation. This is the first
      case described in literature with an early pure epileptic onset, presenting with
      West syndrome. 

PMID- 26194624
TI  - Associations of circulating natriuretic peptides with haemodynamics in
      precapillary pulmonary hypertension.
AB  - BACKGROUND: While N-terminal B-type natriuretic peptide (NT-proBNP) has been
      examined extensively in pulmonary hypertension (PH), limited data exists on the
      subtype A, C and D. The aim of this prospective pilot study was a head-to-head
      comparison of NPs in respect to haemodynamic parameters and the influence of
      renal function. METHODS: Plasma samples were drawn during routine right heart
      catheterization in 62 patients with precapillary PH and 20 control patients. MR
      proANP measurements were performed on the automated Kryptor platform, NT-proBNP
      by CLIA, NT-proCNP and DNP levels by ELISA. Results are expressed as median
      [range] and tested non-parametrically. Non-parametric locally linear multiple
      regression was performed to determine the influence of renal function on NP
      levels. P-values <0.05 were considered significant. RESULTS: Patients with PH had
      significantly higher MR-proANP and NT-proBNP levels. NT-proCNP showed a trend to
      higher levels, while DNP did not differ from control subjects. Both MR-proANP and
      NT-proBNP were associated with cardiac index (CI), right atrial pressure (RAP),
      mean pulmonary artery pressure (PAPm) and pulmonary vascular resistance index
      (PVRI). NT-proCNP was associated with RAP, while DNP showed no associations with
      haemodynamic variables. Associations of haemodynamic parameters with NPs were
      weakened in patients with in elevated serum creatinine and showed increased
      regression slopes. CONCLUSION: MR-proANP demonstrated equivalent associations
      with haemodynamics compared to NT-proBNP, but both markers depend on intact renal
      function. NT-proCNP was correlated with RAP and renal function, while DNP showed
      no associations. Larger studies should evaluate MR-proANP as candidate prognostic
      biomarker in PH.

PMID- 26194626
TI  - Exploring biomolecular dynamics and interactions using advanced sampling methods.
AB  - Molecular dynamics (MD) and Monte Carlo (MC) simulations have emerged as a
      valuable tool to investigate statistical mechanics and kinetics of biomolecules
      and synthetic soft matter materials. However, major limitations for routine
      applications are due to the accuracy of the molecular mechanics force field and
      due to the maximum simulation time that can be achieved in current simulations
      studies. For improving the sampling a number of advanced sampling approaches have
      been designed in recent years. In particular, variants of the parallel tempering
      replica-exchange methodology are widely used in many simulation studies. Recent
      methodological advancements and a discussion of specific aims and advantages are
      given. This includes improved free energy simulation approaches and
      conformational search applications. 

PMID- 26194625
TI  - Towards a mechanistic understanding of carbon stabilization in manganese oxides.
AB  - Minerals stabilize organic carbon (OC) in sediments, thereby directly affecting
      global climate at multiple scales, but how they do it is far from understood.
      Here we show that manganese oxide (Mn oxide) in a water treatment works filter
      bed traps dissolved OC as coatings build up in layers around clean sand grains at
      3%w/wC. Using spectroscopic and thermogravimetric methods, we identify two main
      OC fractions. One is thermally refractory (>550  degrees C) and the other is
      thermally more labile (<550  degrees C). We postulate that the thermal stability
      of the trapped OC is due to carboxylate groups within it bonding to Mn oxide
      surfaces coupled with physical entrapment within the layers. We identify a
      significant difference in the nature of the surface-bound OC and bulk OC . We
      speculate that polymerization reactions may be occurring at depth within the
      layers. We also propose that these processes must be considered in future studies
      of OC in natural systems. 

PMID- 26194627
TI  - [Management of craniofacial type 1 neurofibromatosis].
AB  - Type I neurofibromatosis (NF) is the most common autosomal dominant disease. It
      concerns one in 3000 births, the penetrance is close to 100% and 50% of new cases
      are de novo mutations (17q11.2 chromosome 17 location). Cranio-maxillofacial
      region is concerned in 10% of the cases, in different forms: molluscum
      neurofibroma, plexiform neurofibroma, cranio-orbital neurofibroma, parotido-jugal
      neurofibroma, cervical neurofibroma. These lesions have different prognosis
      depending on the craniofacial localization: ocular functional risk, upper airway
      compressive risk, nerve compression risk, aesthetic and social impact. The
      maxillofacial surgeon in charge of patients with type I NF should follow the
      patient from the diagnosis and organize the different surgical times in order to
      take care about the different issues: vital, functional and aesthetic. We
      describe the treatment of facial localizations of type 1 NF as it is done at the
      University Hospital of Lyon and at the Rhone-Alpes-Auvergne neurofibromatosis
      reference center. 

PMID- 26194628
TI  - Association of Porphyromonas gingivalis with high levels of stress-induced
      hormone cortisol in chronic periodontitis patients.
AB  - AIM: The aim of the present study was to evaluate the association between the
      occurrence of periodontopathogens with cortisol levels in chronic periodontitis
      patients. METHODS: Seventy-five chronic periodontitis patients were invited to
      participate in the present study. Cortisol levels in serum were measured using an
      immunoassay method. Porphyromonas gingivalis (P. gingivalis) Tannerella
      forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans were
      detected by polymerase chain reaction using primers designed to target the
      respective 16S rRNA gene sequences. RESULTS: Severe chronic periodontitis
      patients showed higher mean levels of cortisol (P < 0.05). Twenty-six patients
      had hypercortisolemia. High cortisol levels showed a positive significant
      correlation with P. gingivalis (r = 0.237, P < 0.01). Of the 26 patients with
      hypercortisolemia, 81% had P. gingivalis, of which 86% had severe chronic
      periodontitis (P < 0.001). There were higher levels of cortisol with the presence
      of P. gingivalis (478.65 +/- 122.57 vs 402.58 +/- 139.60, P = 0.01). The adjusted
      logistic regression model showed a significant association between high cortisol
      levels and P. gingivalis (odds ratio = 1.7, 95% confidence interval = 1.6-1.8).
      CONCLUSIONS: This research offers support for the association between P.
      gingivalis and higher levels of cortisol in chronic periodontitis patients. These
      results suggest that high levels of cortisol could increase the occurrence of P.
      gingivalis in the biofilm.

PMID- 26194629
TI  - Amphotericin B and anidulafungin directly interact with DNA and induce oxidative
      damage in the mammalian genome.
AB  - Amphotericin B and anidulafungin are widely used antifungal drugs for the
      treatment of systemic and serious mycoses. Amphotericin B is a relatively toxic
      drug which has long been established. This study is first of its kind to
      systematically investigate the nature of binding to DNA, and to evaluate
      intercalation of AMP-B or ANIDULA with the aid of UV-Vis, ITC, and CD
      spectroscopy. The binding affinity of AMP-B with exclusion sites of 4.68 base
      pairs (1.2 * 10(5) M(-1)) was found to be higher than that of ANIDULA with
      exclusion sites of 6.67 base pairs (3.78 * 10(4) M(-1)); consistent with the
      binding affinity values obtained for AMP-B (10(5) M(-1)) and ANIDULA (10(4) M(
      1)). The binding of two drugs with double-stranded DNA was favoured by negative
      enthalpy as well as negative entropy changes. The intercalation of drugs to
      duplex polynucleotide induced changes in the intrinsic CD spectra and revealed
      comparatively higher affinity towards AMP-B than ANIDULA. Molecular docking
      studies revealed that the negative binding energy was higher in the case of AMP-B
      reflecting more affinity towards single-stranded DNA. The results of the
      cytotoxicity, immunoblotting, and gene specific LA-QPCR assay have indicated that
      ANIDULA is less genotoxic than AMP-B. Hence, the superiority of ANIDULA over AMP
      B as a systemic antifungal drug has been established beyond doubt.

PMID- 26194632
TI  - Abdominal pain symptoms are associated with anxiety and depression in young
      children.
AB  - AIM: Abdominal pain symptoms and incontinence are common in childhood. The aim of
      this study was to analyse abdominal pain symptoms and their associations with
      incontinence and symptoms of anxiety and depression in young children. METHODS:
      We examined 1130 children during the school entry check-up (mean age 6.2 years)
      and 951 participated in the study. Parents completed a questionnaire contained 11
      items regarding Rome-III functional gastrointestinal disorders (FGIDs) and
      incontinence and 14 items from the anxious/depressed scale of the Child Behavior
      Checklist (CBCL). RESULTS: Of the 951 children (55.6% boys) we recruited, 30.1%
      had experienced abdominal pain symptoms in the past two months and 14% had
      complained of them at least once a week. In addition, 2.6% had irritable bowel
      syndrome, 11.3% had childhood functional abdominal pain, 2.4% were affected by
      faecal incontinence, 2.1% were affected by daytime urinary incontinence, and 5.5%
      were affected by nocturnal enuresis. One in ten (10.6%) had symptoms of anxiety
      and depression, and these were significantly higher in the children with FGIDs,
      particularly if they were also incontinent. CONCLUSION: Nearly a third of the
      children (30.1%) had abdominal pain symptoms, and FGIDs were associated with
      significantly higher symptoms of anxiety and depression, especially if children
      were also incontinent.

PMID- 26194633
TI  - Plasmapheresis therapy in ANCA-associated vasculitides: A single-center
      retrospective analysis of renal outcome and mortality.
AB  - BACKGROUND: The evidence of the benefit of plasmapheresis in renal and survival
      outcomes in patients with severe manifestations of ANCA-associated vasculitides
      is inconsistent. PURPOSE: To address whether plasmapheresis is associated with
      improvement in renal function and survival at 12 months in patients with severe
      manifestations of ANCA-associated vasculitides. PATIENTS AND METHODS: Single
      center retrospective comparative cohort of 24 patients with granulomatosis with
      polyangiitis or microscopic polyangiitis that received plasmapheresis adjunctive
      to conventional therapy (steroids and immunosuppressants), matched 1:1 according
      to age, estimated glomerular filtration rate (eGFR) and disease activity with 24
      patients treated with standard treatment only. Comorbidities, demographic,
      clinical, treatment and laboratory characteristics were recorded. RESULTS: After
      12 months both groups showed improvement in eGFR (19.0 +/- 14.34 to 41.61 +/-
      37.77 ml/min, p = 0.003 in plasmapheresis group; 23.16 +/- 14.71 to 39.86 +/-
      25.67 ml/min, p = 0.001 in conventional therapy group). No differences were found
      between groups (p = 0.68). Patients free of dialysis at 12 months after
      intervention increased in the plasmapheresis group from 9/24 (38%) to 12/24
      (50%), p = 0.5; and in the conventional therapy group from 19/24 (79%) to 22/24
      (92%), p = 0.25. Difference between groups was significant at 12 months (p =
      0.001). Survival at 12 months after intervention was 79% in the plasmapheresis
      group and 96% in the conventional therapy group (p = 0.08). The main cause of
      death was infectious and a tendency for a higher prevalence of severe infections
      was observed in patients that received plasmapheresis (p = 0.07). CONCLUSION:
      Both plasmapheresis and conventional therapy improved eGFR at 12 months after
      intervention. Dialysis independence and survival were similar between groups. J.
      Clin. Apheresis 31:411-418, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26194630
TI  - Novel Cathelicidins from Pigeon Highlights Evolutionary Convergence in Avain
      Cathelicidins and Functions in Modulation of Innate Immunity.
AB  - Cathelicidins are short cationic host defense peptides and play a central role in
      host innate immune system. Here we identified two novel cathelicidins, Cl-CATH2
      and 3, from Columba livia. Evolutionary analysis of avian cathelicidins via
      phylogenetic tree and Ka/Ks calculations supported the positive selection that
      prompted evolution of CATH2 to CATH1 and 3, which originate from common ancestor
      and could belong to one superfamily. Cl-CATH2 and 3 both adopt amphipathic alpha
      helical comformations identified by circular dichroism and the 3D structures
      built by Rosetta. Cl-CATH2 of CATH2 family with the most expression abundance in
      bird, exhibited relatively weak antimicrobial activity, but acted instead on the
      innate immune response without showing undesirable toxicities. In macrophages
      primed by LPS, Cl-CATH2 significantly down-regulated the gene and protein
      expressions of inducible nitric oxide synthase and pro-inflammatory cytokines
      while enhancing the anti-inflammatory cytokine, acting through MAPK and NF-kappaB
      signaling pathways. Molecular docking shows for the first time that cathelicidin
      binds to the opening region of LPS-binding pocket on myeloid differentiation
      factor 2 (MD-2) of toll-like receptor (TLR)4-MD-2 complex, which in turn inhibits
      the TLR4 pathway. Our results, therefore, provide new insight into the mechanism
      underlying the blockade of TLR4 signaling by cathelicidins. 

PMID- 26194635
TI  - Wet-chemical synthesis of different bismuth telluride nanoparticles using metal
      organic precursors - single source vs. dual source approach.
AB  - Thermolysis of the single source precursor (Et2Bi)2Te in DIPB at 80  degrees C
      yielded phase-pure Bi4Te3 nanoparticles, while mixtures of Bi4Te3 and elemental
      Bi were formed at higher temperatures. In contrast, cubic Bi2Te particles were
      obtained by thermal decomposition of Et2BiTeEt in DIPB. Moreover, a dual source
      approach (hot injection method) using the reaction of Te(SiEt3)2 and Bi(NMe2)3
      was applied for the synthesis of different pure Bi-Te phases including Bi2Te,
      Bi4Te3 and Bi2Te3, which were characterized by PXRD, REM, TEM and EDX. The
      influence of reaction temperature, precursor molar ratio and thermolysis
      conditions on the resulting material phase was verified. Moreover, reactions of
      alternate bismuth precursors such as Bi(NEt2)3, Bi(NMeEt)3 and BiCl3 with
      Te(SiEt3)2 were investigated. 

PMID- 26194634
TI  - Prospective, randomized, double-blind trial to investigate the efficacy and
      safety of corneal cross-linking to halt the progression of keratoconus.
AB  - BACKGROUND: Corneal cross-linking is widely used to treat keratoconus. However,
      to date, only limited data from randomized trials support its efficacy. METHODS:
      The efficacy and safety of corneal cross-linking for halting progression of
      keratoconus were investigated in a prospective, randomized, blinded, placebo
      controlled, multicentre trial. Twenty-nine keratoconus patients were randomized
      in three trial centres. The mean age at inclusion was 28 years. Longitudinal
      changes in corneal refraction were assessed by linear regression. The best
      corrected visual acuity, surface defects and corneal inflammation were also
      assessed. These data were analysed with a multifactorial linear regression model.
      RESULTS: A total of 15 eyes were randomized to the treatment and 14 to the
      control group. Follow-up averaged 1098 days. Corneal refractive power decreased
      on average (+/-standard deviation) by 0.35 +/- 0.58 dioptres/year in the
      treatment group. The controls showed an increase of 0.11 +/- 0.61 dioptres/year.
      This difference was statistically significant (p = 0.02). CONCLUSIONS: Our data
      suggest that corneal cross-linking is an effective treatment for some patients to
      halt the progression of keratoconus. However, some of the treated patients still
      progressed, whereas some untreated controls improved. Therefore, further
      investigations are necessary to decide which patients require treatment and which
      do not. TRIAL REGISTRATION: NCT00626717, Date of registration: February 20, 2008.

PMID- 26194636
TI  - Siglec-G is a B-1 cell inhibitory receptor and also controls B cell tolerance.
AB  - B cell antigen receptor signaling on B-1 cells is controlled by several
      inhibitory receptors, including Siglec-G, which is a member of the Siglec (sialic
      acid-binding immunoglobulin-like lectin) family and inhibits B cell signaling.
      The inhibitory function of Siglec-G is largely restricted to B-1 cells, as
      demonstrated by studies of Siglec-G-deficient mice showing a phenotype affecting
      mostly B-1 cells. Siglec-G-deficient mice show a markedly increased B-1a cell
      population, enhanced B-1 cell signaling, and a shift in the immunoglobulin
      repertoire secreted by their B-1 cells. Mouse models have provided evidence that
      Siglec-G binds to the B cell receptor (BCR) on the B cell surface via interaction
      with sialic acid ligands. As an inhibitory receptor on B cells, Siglec-G controls
      B cell tolerance, and deficiency of this protein can increase the severity of
      autoimmune diseases. Despite its importance on B-1 cells, there is evidence that
      the control of B cell tolerance by Siglec-G occurs on conventional B-2 cells. 

PMID- 26194637
TI  - [Conclusions].

PMID- 26194638
TI  - The hidden costs of drug and alcohol use in hospital emergency departments.
AB  - INTRODUCTION AND AIMS: This study estimates the burden of drug and alcohol
      morbidity on hospitals in New South Wales (NSW) by observing a multi-site
      collective sample utilising survey information and data linkage. Specifically we
      aimed to determine the prevalence of alcohol and other drug (AOD) problems and to
      estimate patterns of utilisation of hospital services, costs of presentations,
      and admissions for patients with AOD problems. DESIGN AND METHODS: Patients were
      recruited from eight NSW public hospitals presenting to the hospital emergency
      department over a 10 day period. Participants completed a self-administered
      survey with demographic characteristics and questions about substance use. More
      than two-thirds (68%) of participants consented to provide access to their NSW
      Health medical data for a period spanning 2.5 years. RESULTS: One-third (35%) of
      the total sample were identified as having problematic AOD use with one in five
      of these patients requiring a high level of intervention. Those patients
      requiring a high level of intervention present more often and cost more per
      presentation. If admitted they were more likely to have longer stays and were
      also more likely to be admitted to a psychiatric ward and have a longer stay in
      the ward. DISCUSSION: This study demonstrates a need for AOD interventions in the
      emergency department setting, both because it represents an opportunity for
      intervention in a population in which problems with substance use is highly
      prevalent, and because there is evidence that AOD imposes additional costs on the
      health system. [Butler K, Reeve R, Arora S, Viney R, Goodall S, van Gool K, Burns
      L. The hidden costs of drug and alcohol use in hospital emergency departments.
      Drug Alcohol Rev 2016;35:359-366].

PMID- 26194639
TI  - Laboratory investigation of the microbiologically influenced corrosion (MIC)
      resistance of a novel Cu-bearing 2205 duplex stainless steel in the presence of
      an aerobic marine Pseudomonas aeruginosa biofilm.
AB  - The microbiologically influenced corrosion (MIC) resistance of a novel Cu-bearing
      2205 duplex stainless steel (2205 Cu-DSS) against an aerobic marine Pseudomonas
      aeruginosa biofilm was investigated. The electrochemical test results showed that
      Rp increased and icorr decreased sharply after long-term immersion in the
      inoculation medium, suggesting that 2205 Cu-DSS possessed excellent MIC
      resistance to the P. aeruginosa biofilm. Fluorescence microscope images showed
      that 2205 Cu-DSS possessed a strong antibacterial ability, and its antibacterial
      efficiency after one and seven days was 7.75% and 96.92%, respectively. The pit
      morphology comparison after 14 days between 2205 DSS and 2205 Cu-DSS demonstrated
      that the latter showed a considerably reduced maximum MIC pit depth compared with
      the former (1.44 MUm vs 9.50 MUm). The experimental results suggest that
      inhibition of the biofilm was caused by the copper ions released from the 2205 Cu
      DSS, leading to its effective mitigation of MIC by P. aeruginosa.

PMID- 26194640
TI  - Enhancing the Role of the Nurse in Primary Care: The RN "Co-Visit" Model.

PMID- 26194641
TI  - That Which Bends Up: A Case Report and Literature Review of Chikungunya Virus.
AB  - We present a case of chikungunya virus (CHIKV) in a 39-year-old female who
      developed an acute febrile illness marked by polyarthralgia and rash after
      returning from Saint Lucia. This epidemic-prone pathogen is increasingly likely
      to be encountered by primary care and hospital physicians in the coming months.
      The virus was first locally transmitted in the Caribbean in December 2013 and has
      since spread to 44 countries and 47 US states, affecting a suspected 1.2 million
      people. A mosquito-borne virus, CHIKV causes a severe and symmetric
      polyarthralgia that can relapse for months to years, creating debilitating
      illness and profound socioeconomic consequences. Current treatment is limited to
      supportive measures, which are dependent on nonsteroidal anti-inflammatory drugs.
      Research into immunomodulatory agents, antiviral therapies, and vaccines is
      ongoing. Prevention remains key in slowing the spread of disease. Patient
      education should focus on personal protective measures, such as insect repellant
      and remaining indoors, while public health departments should implement
      strategies to control vector breeding grounds. Given the possibility of relapsing
      and debilitating disease, general internists should consider CHIKV in the
      differential diagnosis of a returning traveler with acute onset of fever,
      polyarthralgia, and rash. 

PMID- 26194642
TI  - Triamterene Enhances the Blood Pressure Lowering Effect of Hydrochlorothiazide in
      Patients with Hypertension.
AB  - BACKGROUND: Triamterene, because of its potassium-sparing properties, is
      frequently used in combination with hydrochlorothiazide (HCTZ) to treat patients
      with hypertension. By inhibiting the epithelial sodium channel (ENaC) in the
      cortical collecting duct, triamterene reduces potassium secretion, thus reducing
      the risk of hypokalemia. Whether triamterene has an independent effect on blood
      pressure (BP) has not been well studied. OBJECTIVE: To determine if triamterene
      provides an effect to further lower BP in patients treated with HCTZ. DESIGN: We
      conducted an observational study using electronic medical record data from the
      Indiana Network for Patient Care. Participants were 17,291 patients with the
      diagnosis of hypertension between 2004 and 2012. MAIN MEASURES: BP was the
      primary outcome. We compared the BP between patients who were taking HCTZ, with
      and without triamterene, either alone or in combination with other
      antihypertensive medications, by using a propensity score analysis. For each
      medication combination, we estimated the propensity score (i.e., probability) of
      a patient receiving triamterene using a logistic regression model. Patients with
      similar propensity scores were stratified into subclasses and BP was compared
      between those taking triamterene or not within each subclass; the effect of
      triamterene was then assessed by combining BP differences estimated from all
      subclasses. KEY RESULTS: The mean systolic BP in the triamterene + HCTZ group was
      3.8 mmHg lower than in the HCTZ only group (p < 0.0001); systolic BP was
      similarly lower for patients taking triamterene with other medication
      combinations. Systolic BP reduction was consistently observed for different
      medication combinations. The range of systolic BP reduction was between 1 and 4
      mm Hg, depending on the concurrently used medications. CONCLUSIONS: In the
      present study, triamterene was found to enhance the effect of HCTZ to lower BP.
      In addition to its potassium-sparing action, triamterene's ability to lower BP
      should also be considered.

PMID- 26194643
TI  - Double-burden of malnutrition among the indigenous peoples (Orang Asli) of
      Peninsular Malaysia.
AB  - BACKGROUND: Double-burden of malnutrition (DBM) is an emerging public health
      concern among the Orang Asli (indigenous peoples) of Peninsular Malaysia. This
      study aimed to identify the presence of DBM at the community and household levels
      in Orang Asli population and its associated demographic and socio-economic
      factors. METHODS: This cross-sectional study was conducted in 11 Orang Asli
      villages surrounding the Krau Wildlife Reserve, Peninsular of Malaysia from
      October 2011 to January 2012. Of 438 households, a total of 981 adults and 304
      children who met the study criteria agreed to participate. About 160 households
      were further selected with pairs of children aged 3-59 months and non-pregnant
      mothers aged 15-55 years. Demographic and socio-economic data were obtained using
      interviewer-administered questionnaire while weight and height were measured
      using standard procedures. Double-burden of malnutrition was defined as
      overweight/obese mother-underweight child (OWOBM/UWC), overweight/obese mother
      stunted child (OWOBM/STC) or overweight/obese mother-underweight or/and stunted
      child (OWOBM/UWSTC). Binary logistic regression identified the demographic and
      socio-economic factors associated with double-burden households. RESULTS: About
      26 % of overweight and obese adults coexisting with high proportions of
      underweight (49%) and stunted (64%) children in these Orang Asli villages. There
      was a higher prevalence of households with OWOBM/UWSTC (20%) and OWOBM/STC
      (19.4%) than households with OWOBM/UWC (12.5%). Boys (P < 0.05), older age
      mothers (P < 0.05), mothers with higher education (P < 0.05) and households with
      income per capita less than USD 29.01 (RM 97.00) (P < 0.01) were associated with
      higher odds of OWOBM/STC. Jah Hut (P < 0.05) and higher number of children (P <
      0.05) were significantly associated with lower odds of OWOBM/UWC. CONCLUSIONS:
      The occurrence of double-burden of malnutrition in Orang Asli population deserves
      attention. Poverty reduction, access to quality diet and improved health and
      nutrition literacy are among strategies that could address the coexistence of DBM
      in this population.

PMID- 26194644
TI  - Reporter cell lines for skin sensitization testing.
AB  - Skin sensitization has been described as an adverse outcome pathway (AOP),
      comprising a number of molecular events leading to the final adverse effect. In a
      new paradigm of toxicology, attempts are made to collect information using single
      mechanistic tests addressing different targets along such an AOP and to then
      integrate this information to arrive at a final toxicological prediction. This
      proposal is strongly influenced by the availability of methods for high
      throughput screening of cellular events. Reporter cell lines are a particularly
      useful tool in such screening paradigms, as they can deliver highly reproducible
      and easily measureable results, and they can be designed to quantify induction or
      suppression at the transcription level of very specific molecular targets within
      cells. The first cell-based assay for skin sensitization, which has recently
      received ECVAM and OECD endorsement, is the reporter cell assay KeratinoSensTM,
      reflecting activation of the Nrf2 pathway, and other assays measuring the Nrf2
      pathway are under development or validation. An alternative approach (THP-G8) was
      recently developed based on activation of the Interleukin-8 gene. Here, we review
      these assays, their role in the AOP, their mechanistic interrelationships, their
      use for hazard and risk assessment, and their application in integrated testing
      strategies. At the same time, this study reviews (1) other cellular markers for
      sensitizers, and the potential to develop new reporter gene assays providing
      additional, non-redundant information, and (2) it presents approaches and new
      experimental data on attempts to further improve the predictivity of the existing
      assay. 

PMID- 26194645
TI  - Association of Nrf2 with airway pathogenesis: lessons learned from genetic mouse
      models.
AB  - Nrf2 is a key transcription factor for antioxidant response element (ARE)-bearing
      genes involved in diverse host defense functions including redox balance, cell
      cycle, immunity, mitochondrial biogenesis, energy metabolism, and carcinogenesis.
      Nrf2 in the airways is particularly essential as the respiratory system
      continuously interfaces with environmental stress. Since Nrf2 was determined to
      be a susceptibility gene for a model of acute lung injury, its protective
      capacity in the airways has been demonstrated in experimental models of human
      disorders using Nrf2 mutant mice which were susceptible to supplemental
      respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke,
      allergens, virus, environmental pollutants, and fibrotic agents compared to wild
      type littermates. Recent studies also determined that Nrf2 is indispensable in
      developmental lung injury. While association studies with genetic NRF2
      polymorphisms supported a protective role for murine Nrf2 in oxidative airway
      diseases, somatic NRF2 mutations enhanced NRF2-ARE responses, and were favorable
      for lung carcinogenesis and chemoresistance. Bioinformatic tools have elucidated
      direct Nrf2 targets as well as Nrf2-interacting networks. Moreover, potent Nrf2
      ARE agonists protected oxidant-induced lung phenotypes in model systems,
      suggesting a therapeutic or preventive intervention. Further investigations on
      Nrf2 should yield greater understanding of its contribution to normal and
      pathophysiological function in the airways. 

PMID- 26194647
TI  - Impact of a synthetic cannabinoid (CP-47,497-C8) on protein expression in human
      cells: evidence for induction of inflammation and DNA damage.
AB  - Synthetic cannabinoids (SCs) are marketed worldwide as legal surrogates for
      marihuana. In order to predict potential health effects in consumers and to
      elucidate the underlying mechanisms of action, we investigated the impact of a
      representative of the cyclohexylphenols, CP47,497-C8, which binds to both
      cannabinoid receptors, on protein expression patterns, genomic stability and on
      induction of inflammatory cytokines in human lymphocytes. After treatment of the
      cells with the drug, we found pronounced up-regulation of a variety of enzymes in
      nuclear extracts which are involved in lipid metabolism and inflammatory
      signaling; some of the identified proteins are also involved in the endogenous
      synthesis of endocannabinoids. The assumption that the drug causes inflammation
      is further supported by results obtained in additional experiments with cytosols
      of LPS-stimulated lymphocytes which showed that the SC induces pro-inflammatory
      cytokines (IL12p40 and IL-6) as well as TNF-alpha. Furthermore, the proteome
      analyses revealed that the drug causes down-regulation of proteins which are
      involved in DNA repair. This observation provides an explanation for the
      formation of comets which was seen in single-cell gel electrophoresis assays and
      for the induction of micronuclei (which reflect structural and numerical
      chromosomal aberrations) by the drug. These effects were seen in experiments with
      human lymphocytes which were conducted under identical conditions as the proteome
      analysis. Taken together, the present findings indicate that the drug (and
      possibly other structurally related SCs) may cause DNA damage and inflammation in
      directly exposed cells of consumers. 

PMID- 26194646
TI  - Toxicogenomic assessment of liver responses following subchronic exposure to
      furan in Fischer F344 rats.
AB  - Furan is a widely used industrial chemical and a contaminant in heated foods.
      Chronic furan exposure causes cholangiocarcinoma and hepatocellular tumors in
      rats at doses of 2 mg/kg bw/day or greater, with gender differences in frequency
      and severity. The hepatic transcriptional alterations induced by low doses of
      furan (doses below those previously tested for induction of liver tumors) and the
      potential mechanisms underlying gender differences are largely unexplored. We
      used DNA microarrays to examine the global hepatic mRNA and microRNA
      transcriptional profiles of male and female rats exposed to 0, 0.03, 0.12, 0.5 or
      2 mg/kg bw/day furan over 90 days. Marked gender differences in gene expression
      responses to furan were observed, with many more altered genes in exposed males
      than females, confirming the increased sensitivity of males even at the low
      doses. Pathway analysis supported that key events in furan-induced liver tumors
      in males include gene expression changes related to oxidative stress, apoptosis
      and inflammatory response, while pathway changes in females were consistent with
      primarily adaptive responses. Pathway benchmark doses (BMDs) were estimated and
      compared to relevant apical endpoints. Transcriptional pathway BMDs could only be
      examined in males. These median BMDs ranged from 0.08 to 1.43 mg/kg bw/day and
      approximated those derived from traditional histopathology. MiR-34a (a P53
      target) was the only microRNA significantly increased at the 2 mg/kg bw/day,
      providing evidence to support the importance of apoptosis and cell proliferation
      in furan hepatotoxicity. Overall, this study demonstrates the use of
      transcriptional profiling to discern mode of action and mechanisms involved in
      gender differences. 

PMID- 26194649
TI  - Molecular epidemiology and genetic diversity of Blastocystis infection in humans
      in Italy.
AB  - In order to describe the molecular epidemiology of Blastocystis infection in
      Italy, 189 isolates, which had been collected during the years 2012-2014 from
      mildly symptomatic patients, or those affected by inflammatory bowel disease
      (IBD), irritable bowel syndrome (IBS) or chronic diarrhoea, or otherwise
      immunosuppressed, were subtyped by sequence analysis of the SSU rRNA gene (536
      bp). Six subtypes (STs) were detected: ST1 (15.3%), ST2 (13.8%), ST3 (46.0%), ST4
      (21.7%), ST6 (3.2%) and ST8 (0.5%). They clustered in distinct clades, as
      inferred from Bayesian inference phylogenetic and median joining network
      analyses. A high genetic differentiation was found at the inter-subtype level; it
      ranged from Jukes-Cantor (JC) distance = 0.02 (between ST1 and ST4) to JC = 0.11
      (between ST6 and ST2). At the intra-ST level, a high genetic homogeneity was
      registered in ST4, whereas higher genetic variation was found in isolates
      corresponding to ST1 and ST2. Accordingly, high values of haplotype and
      nucleotide diversity were observed in ST1, ST2 and ST3. No association was found
      between patient gender and ST, whereas ST3 and ST1 were significantly more
      prevalent in patients aged 15-50 years. A significant occurrence of Blastocystis
      ST4 in patients suffering from IBS, IBD or chronic diarrhoea was observed; in
      addition, a slight significant association between ST1 and ST3 and IBS patients
      was found. Multiple correspondence analysis showed some significant contribution
      of different variables (subtypes, haplotypes, age) in the observed pattern of
      ordination of the 189 patients in the symptom categories. 

PMID- 26194648
TI  - Design of a study to determine the impact of insecticide resistance on malaria
      vector control: a multi-country investigation.
AB  - BACKGROUND: Progress in reducing the malaria disease burden through the
      substantial scale up of insecticide-based vector control in recent years could be
      reversed by the widespread emergence of insecticide resistance. The impact of
      insecticide resistance on the protective effectiveness of insecticide-treated
      nets (ITN) and indoor residual spraying (IRS) is not known. A multi-country study
      was undertaken in Sudan, Kenya, India, Cameroon and Benin to quantify the
      potential loss of epidemiological effectiveness of ITNs and IRS due to decreased
      susceptibility of malaria vectors to insecticides. The design of the study is
      described in this paper. METHODS: Malaria disease incidence rates by active case
      detection in cohorts of children, and indicators of insecticide resistance in
      local vectors were monitored in each of approximately 300 separate locations
      (clusters) with high coverage of malaria vector control over multiple malaria
      seasons. Phenotypic and genotypic resistance was assessed annually. In two
      countries, Sudan and India, clusters were randomly assigned to receive universal
      coverage of ITNs only, or universal coverage of ITNs combined with high coverage
      of IRS. Association between malaria incidence and insecticide resistance, and
      protective effectiveness of vector control methods and insecticide resistance
      were estimated, respectively. RESULTS: Cohorts have been set up in all five
      countries, and phenotypic resistance data have been collected in all clusters. In
      Sudan, Kenya, Cameroon and Benin data collection is due to be completed in 2015.
      In India data collection will be completed in 2016. DISCUSSION: The paper
      discusses challenges faced in the design and execution of the study, the analysis
      plan, the strengths and weaknesses, and the possible alternatives to the chosen
      study design.

PMID- 26194650
TI  - [Reversible cerebral vasoconstriction syndrome. Challenge for diagnostics and
      intensive care therapy].
AB  - Reversible cerebral vasoconstriction syndrome (RCVS) is a disease of unclear
      incidence frequently affecting middle aged women and is usually associated with
      use of adrenergic or serotoninergic substances. The exclusion of relevant
      differential diagnoses, such as aneurysmal subarachnoid hemorrhage, primary
      cerebral angiitis, posterior reversible encephalopathy syndrome and carotid
      artery dissection is critical in terms of time and significance. Thunderclap
      headache as well as multiple and multilocular vasospasms with direct or indirect
      angiography without substantial findings in cerebrospinal fluid diagnostics are
      typical symptoms. The necessity for intensive care treatment is often justified
      by initial acute impairment of vital functions and possible development of
      cerebral or extracerebral complications. Because the exact pathophysiology
      remains unknown, a specific therapy does not exist. This poses significant
      challenges in intensive care medicine, which are illustrated on the basis of the
      case study presented. 

PMID- 26194651
TI  - [Acute non-allergic angioedema. Rare cause for intensive care unit admission].
AB  - Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema usually follows
      an uneventful clinical course; however, if upper airway structures are involved,
      life-threatening complications may develop. Thus, affected patients should be
      carefully monitored in an intensive care unit and, if need be, the airway has to
      be secured early on. This case report discusses diagnostic and therapeutic
      approaches in a patient with suspected ACE inhibitor-induced angioedema, who had
      initially been admitted for neoadjuvant radiochemotherapy of rectal cancer. 

PMID- 26194652
TI  - [Perioperative thermal management in Germany varies depending on the hospital
      size].
AB  - BACKGROUND: Improvement of quality of care and patient safety while decreasing
      costs are major challenges in healthcare systems. This challenge includes the
      avoidance of perioperative hypothermia to reduce the associated adverse effects,
      length of stay and treatment costs. Due to the medical and economic relevance the
      national S3 guidelines for the prevention of perioperative hypothermia were
      recently published. AIM: This study presents and analyses the reality of
      utilization of thermal management in German hospitals depending on the size of
      the hospital, which is based on the number of beds. MATERIAL AND METHODS: Based
      on the data of an online survey among all members of the German Society of
      Anesthesiology and Intensive Care Medicine about perioperative thermal
      management, a subgroup analysis differentiating between the size of hospitals was
      performed. The survey included questions about the structural and organizational
      conditions, the practical implementation of temperature measurement and warming
      therapy and the developmental status of clinical standard operating procedures
      (SOP) and educational training. RESULTS: Comparing the structural quality, major
      differences were found with respect to the availability of core body temperature
      measurement and the provision of warming devices especially at different
      peripheral anesthesia workplaces as well as the existence of SOPs and educational
      training. The availability increased with hospital size. With respect to process
      quality, the frequency of prewarming increased with hospital size as well as the
      frequency of intraoperative temperature measurements during different anesthesia
      procedures. CONCLUSION: Major differences were found in several aspects of
      perioperative thermal management depending on the hospital size. The main
      potential for improvement was found in smaller hospitals. Developmental needs
      primarily exist in the configuration of peripheral anesthesia workplaces,
      educational training, implementation of SOPs and prewarming of patients.

PMID- 26194653
TI  - [Venoarterial extracorporeal membrane oxygenation for out-of-hospital cardiac
      arrest. Case series of prehospital and in-hospital therapies].
AB  - Despite new concepts and strategies of basic and advanced life support, the
      outcome of patients with out-of-hospital cardiac arrest (OHCA) remains poor. The
      main reason accounting for these poor results is a low-flow phase during
      conventional cardiopulmonary resuscitation (CPR) with insufficient end organ
      perfusion. The early use of venoarterial extracorporeal membrane oxygenation
      (vaECMO) during CPR, i.e. extracorporeal resuscitation (ECPR) might improve OHCA
      survival rates as well as the neurological outcome in resuscitated patients. This
      article on a case series discusses the management of ECPR in three patients with
      OHCA. All patients suffered from a witnessed OHCA and received effective
      bystander CPR. After subsequent advanced cardiac life support could not achieve a
      return of spontaneous circulation (ROSC), vaECMO support was established as a
      bridge to therapy on site or after transportation to a primary or tertiary
      hospital. During the course of therapy two patients died and one patient was
      discharged after a full recovery. Early ECPR might improve the outcome in
      patients with prolonged cardiac arrest without ROSC. The use of ECPR should be
      based on the individual decision of an experienced ECPR team considering defined
      inclusion and exclusion criteria. As the outcome mainly depends on the duration
      and quality of conventional CPR, ECPR support should be requested immediately
      after establishing advanced life support (approximately 10-15 min). 

PMID- 26194654
TI  - [Individualized coagulation therapy: Wish or already reality?].

PMID- 26194655
TI  - Effects of an 8-Week Outdoor Brisk Walking Program on Fatigue in Hi-Tech Industry
      Employees: A Randomized Control Trial.
AB  - Over 73% of hi-tech industry employees in Taiwan lack regular exercise. They are
      exposed to a highly variable and stressful work environment for extended periods
      of time, and may subsequently experience depression, detrimental to workers'
      physiological and mental health. In this cross-sectional survey, the authors
      explored the effect of an 8-week brisk walking program on the fatigue of
      employees in the hi-tech industry. The participants, from a hi-tech company in
      northern Taiwan, were randomly assigned to an experimental group (EG; 41
      subjects, Mage = 33.34 +/- 6.40) or control group (CG; 45 subjects, Mage = 29.40
      +/- 3.60). Following the 8-week brisk walking program, the EG showed
      significantly lower scores for subjective fatigue, working motivation, attention,
      and overall fatigue. The authors confirmed that the 8-week outdoor brisk walking
      program significantly improved the level of fatigue among employees of the hi
      tech industry. The finding serves as an important reference for health
      authorities in Taiwan and provides awareness of workplace health promotion in the
      hi-tech industry. 

PMID- 26194656
TI  - Bispectral index-guided general anaesthesia in combination with interscalene
      block reduces desflurane consumption in arthroscopic shoulder surgery: a clinical
      comparison of bupivacaine versus levobupivacaine.
AB  - BACKGROUND: The goal of this study was to compare the influence of an
      interscalene brachial plexus block (ISB) performed with either bupivacaine or
      levobupivacaine in conjunction with general anaesthesia (GA) on desflurane
      consumption, which was titrated to maintain the recovery profiles and
      postoperative analgesia while also keeping the bispectral index score (BIS)
      between 40 and 60 in patients undergoing arthroscopic shoulder surgery. METHODS:
      Sixty patients undergoing arthroscopic shoulder surgery were prospectively
      randomized to receive GA with desflurane alone (group C) or in combination with a
      preoperative ISB by either bupivacaine 0.25 % (group B) 40 ml or levobupivacaine
      0.25 % (group L) 40 ml. BIS scores or respiratory and hemodynamic parameters
      during the operation, recovery characteristics, consumed doses of desflurane and
      pain intensities were evaluated. RESULTS: The eye opening time was 4.0 +/- 2.5
      minutes for group B, 4.6 +/- 2.4 minutes for group L, and 6.2 +/- 2.1 minutes for
      group C (p < 0.05). Group B and group L saved 36 % and 25 % desflurane per unit
      time respectively when compared with group C (p < 0.001and p < 0.05) while the
      mean pain scores and analgesic requirements the first day after surgery were
      higher in group C (p < 0.05). CONCLUSIONS: Because of lower desflurane
      consumption, a superior recovery profile, and a high degree of patient
      acceptance, general anaesthesia in combination with interscalene block may be
      preferred in arthroscopic shoulder surgery. TRIAL REGISTRATION: The trial
      registration number is ACTRN12613000381785.

PMID- 26194657
TI  - Tissue microRNA-126 expression level predicts outcome in human osteosarcoma.
AB  - BACKGROUND: MicroRNA-126 has been found to be consistently under-expressed in
      osteosarcoma tissues and cell lines compared with normal bone tissues and normal
      osteoblast cells, respectively. The purpose of the present study was to detect
      the expression levels of miR-126 in osteosarcoma patients and to further
      investigate the clinicopathological, and prognostic value of miR-126. METHODS: We
      recruited 122 patients with osteosarcomas from the Department of Orthopedic
      Surgery, Yantaishan Hospital between May 2008 and April 2013. The expression
      level of miR-126 was determined by qRT-PCR. Associations between miR-126
      expression and various clinicopathological characteristics were analyzed using
      the chi (2) test. Survival rate was determined with Kaplan-Meier and
      statistically analyzed with the log-rank method between groups. Survival data
      were evaluated through multivariate Cox regression analysis. RESULTS: miR-126
      expression was significantly decreased in osteosarcoma tissues compared to
      adjacent normal bone tissues (2.421 +/- 1.250 vs. 6.212 +/- 1.843, P = 0.001). We
      found that low miR-126 expression had significant association with advanced TNM
      stage (P <0.001), distant metastasis (P <0.001), and higher tumor grade (P =
      0.001). Kaplan-Meier survival analysis showed that the miR-126 low-expression
      group had significantly shorter overall survival time than those with high
      expression (log-rank test, P = 0.008). Furthermore, multivariate Cox proportional
      hazards model analysis showed that miR-126 expression was independently
      associated with overall survival of patients with osteosarcoma (HR = 3.102, 95 %
      CI: 1.113-9.023, P = 0.018). CONCLUSIONS: This is the first study revealing that
      miR-126 down-expression may be related to the prediction of poor prognosis for
      osteosarcoma patients, suggesting that miR-126 may serve as a prognostic marker
      for the optimization of clinical treatments.

PMID- 26194658
TI  - MLVA as an Epidemiological Tool To Trace Back Brucella melitensis Biovar 1 Re
      Emergence in Italy.
AB  - Brucellosis is an important zoonosis caused by Brucella spp., still prevalent in
      most areas of the world. Brucellosis control in animals is the key to protect
      humans. The knowledge of Brucella spp. prevailing genotypes in a territory
      represents an important epidemiological tool to formulate policies and strategies
      for disease control and to trace back the introduction of new strains previously
      considered as exotic. In the last years, multiple-locus variable number tandem
      repeat analysis (MLVA) has been proposed as complementary to classical biotyping
      methods. MLVA may add important information to the classical epidemiological
      investigation techniques, to help in tracing back sources of infection in
      brucellosis outbreaks. Sardinia is an Italian region officially free from sheep
      and goats brucellosis since 1998. In 2011, Brucella melitensis biovar 1, a
      biotype not reported in Italy since 1995, was isolated in one flock in the
      region. The genotyping MLVA-16 showed that isolates belonged to a rare American
      lineage, confirming it was introduced from other countries. The strain was
      considered as probably originating from Spain, where this lineage is endemic.
      BrucellaMLVA-16 has been proved to be useful to analyse the epidemiological
      correlation of strains enabling to trace its geographic origin by comparing their
      previously reported genetic patterns.

PMID- 26194659
TI  - Increment of subcutaneous adipose tissue is associated with decrease of elastic
      fibres in the dermal layer.
AB  - Obesity is a significant risk factor for various skin disorders, including
      pressure ulcer and delayed wound healing. We previously showed that increment of
      subcutaneous adipose tissue contributes to poor skin condition by decreasing
      dermal elasticity. Here, we examined the mechanism involved. Histologic
      observation of abdominal skin from middle-aged females with a wide range of body
      mass index (BMI), an indicator of subcutaneous fat mass, showed that dermal
      elastic fibre abundance was significantly decreased with increment of BMI.
      Concomitantly, adipocytes were significantly enlarged. Adipocyte enlargement was
      significantly negatively correlated with dermal elastic fibre abundance. We
      hypothesized that enlarged adipocytes negatively influence dermal elastic fibres,
      so we investigated elastic fibre-degrading factors in in vitro-cultured enlarged
      adipocytes. MMP9 gene expression and secretion were significantly increased;
      further, these changes were blocked by extracellular signal-regulated kinase
      (ERK) inhibitor. Nuclear translocation (activation) of AP-1, a downstream ERK
      signalling molecule, was also observed in enlarged adipocytes. MMP9 abundance was
      significantly increased in skin of subjects with high BMI and enlarged
      adipocytes. These results suggest that increment of subcutaneous adipose tissue
      leads to adipocyte enlargement together with increased degradation of dermal
      elastic fibres, mediated at least in part by an ERK signalling-mediated increase
      of MMP9 in enlarged adipocytes.

PMID- 26194661
TI  - Letters Regarding the TARGIT-A Trial: The Editor's Introduction.

PMID- 26194660
TI  - Serum concentrations of chlorinated dibenzo-p-dioxins, furans and PCBs, among
      former phenoxy herbicide production workers and firefighters in New Zealand.
AB  - PURPOSE: To quantify serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) and dioxin-like compounds in former phenoxy herbicide production plant
      workers and firefighters, 20 years after 2,4,5-T production ceased. METHODS: Of
      1025 workers employed any time during 1969-1984, 430 were randomly selected and
      invited to take part in a morbidity survey and provide a blood sample; 244 (57%)
      participated. Firefighters stationed in close proximity of the plant and/or
      engaged in call-outs to the plant between 1962 and 1987 also participated (39 of
      70 invited). Reported here are the serum concentrations of TCDD and other
      chlorinated dibenzo-dioxins, dibenzofurans, and polychlorinated biphenyls (PCBs).
      Determinants of the serum concentrations were assessed using linear regression.
      RESULTS: The 60 men who had worked in the phenoxy/TCP production area had a mean
      TCDD serum concentration of 19.1 pg/g lipid, three times the mean concentration
      of the 141 men and 43 women employed in other parts of the plant (6.3 and 6.0
      pg/g respectively), and more than 10 times the mean for the firefighters (1.6
      pg/g). Duration of employment in phenoxy herbicide synthesis, maintenance work,
      and work as a boilerman, chemist, and packer were associated with increased serum
      concentrations of TCDD and 1,2,3,4,7-pentachlorodibenzo-p-dioxin (PeCDD).
      Employment as a boilerman was also associated with elevated serum concentrations
      of PCBs. CONCLUSIONS: Occupations in the plant associated with phenoxy herbicide
      synthesis had elevated levels of TCDD and PeCDD. Most other people working within
      the plant, and the local firefighters, had serum concentrations of dioxin-like
      compounds comparable to those of the general population.

PMID- 26194662
TI  - In Regard to Vaidya et al.

PMID- 26194663
TI  - In Regard to Hepel and Wazer.

PMID- 26194664
TI  - In Regard to Vaidya et al.

PMID- 26194665
TI  - In Regard to Hepel and Wazer.

PMID- 26194666
TI  - In Regard to Vaidya et al.

PMID- 26194667
TI  - In Regard to Hepel and Wazer.

PMID- 26194668
TI  - In Regard to Vaidya et al.

PMID- 26194669
TI  - In Regard to Vaidya et al.

PMID- 26194670
TI  - In Regard to Vaidya et al.

PMID- 26194671
TI  - In Regard to Hepel and Wazer.

PMID- 26194672
TI  - Is Less, More? The Evolving Role of Radiation Therapy for Brain Metastases.

PMID- 26194673
TI  - Shine a Light or Back to the Basement?

PMID- 26194674
TI  - Employment After Radiation Oncology Residency: A Survey of the Class of 2014.

PMID- 26194675
TI  - Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma
      in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus
      Standard Radiation Therapy and Maintenance Chemotherapy.
AB  - PURPOSE: In the European HIT-SIOP PNET4 randomized controlled trial, children
      with standard risk medulloblastoma were allocated to hyperfractionated radiation
      therapy (HFRT arm, including a partially focused boost) or standard radiation
      therapy (STRT arm), followed, in both arms, by maintenance chemotherapy. Event
      free survival was similar in both arms. Previous work showed that the HFRT arm
      was associated with worse growth and better questionnaire-based executive
      function, especially in children <8 years of age at diagnosis. Therefore, the aim
      of this study was to compare performance-based cognitive outcomes between
      treatment arms. METHODS AND MATERIALS: Neuropsychological data were collected
      prospectively in 137 patients. Using the Wechsler Intelligence Scales, Kaufman
      Assessment Battery for Children, and Raven's Progressive Matrices, we estimated
      full-scale intelligence quotient (FSIQ) and, when available, verbal IQ (VIQ),
      performance IQ (PIQ), working memory index (WMI), and processing speed index
      (PSI). RESULTS: Among the 137 participants (HFRT arm n=71, STRT arm n=66, 63.5%
      males), mean (+/-SD) ages at diagnosis and assessment respectively were 9.3 (+/
      3.2) years of age (40.8% < 8 years of age at diagnosis) and 14.6 (+/-4.3) years
      of age. Mean (+/-SD) FSIQ was 88 (+/-19), and mean intergroup difference was 3.88
      (95% confidence interval: -2.66 to 10.42, P=.24). No significant differences were
      found in children >8 years of age at diagnosis. In children <8 years of age at
      diagnosis, a marginally significant trend toward higher VIQ was found in those
      treated in the HFRT arm; a similar trend was found for PSI but not for PIQ, WMI,
      or FSIQ (mean intergroup differences were: 12.02 for VIQ [95% CI: 2.37-21.67;
      P=.02]; 3.77 for PIQ [95% CI: -5.19 to 12.74; P>.10]; 5.20 for WMI [95% CI: -2.07
      to 12.47; P>.10]; 10.90 for PSI [95% CI: -1.54 to 23.36; P=.08]; and 5.28 for
      FSIQ [95% CI: -4.23 to 14.79; P>.10]). CONCLUSIONS: HFRT was associated with
      marginally higher VIQ in children <8 years of age at diagnosis, consistent with a
      previous report using questionnaire-based data. However, overall cognitive
      ability was not significantly different.

PMID- 26194676
TI  - A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone
      Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma.
AB  - PURPOSE: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase
      inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to
      radiation in preclinical models. We evaluated the addition of VPA to standard
      radiation therapy (RT) plus temozolomide (TMZ) in patients with newly diagnosed
      GBM. METHODS AND MATERIALS: Thirty-seven patients with newly diagnosed GBM were
      enrolled between July 2006 and April 2013. Patients received VPA, 25 mg/kg
      orally, divided into 2 daily doses concurrent with RT and TMZ. The first dose of
      VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and
      subsequently increased up to 25 mg/kg/day over the week prior to radiation. VPA-
      and TMZ-related acute toxicities were evaluated using Common Toxicity Criteria
      version 3.0 (National Cancer Institute Cancer Therapy Evaluation Program) and
      Cancer Radiation Morbidity Scoring Scheme for toxicity and adverse event
      reporting (Radiation Therapy Oncology Group/European Organization for Research
      and Treatment). RESULTS: A total of 81% of patients took VPA according to
      protocol. Median overall survival (OS) was 29.6 months (range: 21-63.8 months),
      and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2
      months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at
      6, 12, and 24 months was 70%, 43%, and 38% respectively. The most common grade
      3/4 toxicities of VPA in conjunction with RT/TMZ therapy were blood and bone
      marrow toxicity (32%), neurological toxicity (11%), and metabolic and laboratory
      toxicity (8%). Younger age and class V recursive partitioning analysis (RPA)
      results were significant for both OS and PFS. VPA levels were not correlated with
      grade 3 or 4 toxicity levels. CONCLUSIONS: Addition of VPA to concurrent RT/TMZ
      in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may
      result in improved outcomes compared to historical data and merits further study.

PMID- 26194677
TI  - Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain
      Irradiation, for New Brain Metastases After Initial SRS.
AB  - PURPOSE: To report the outcomes of repeat stereotactic radiosurgery (SRS),
      deferring whole-brain radiation therapy (WBRT), for distant intracranial
      recurrences and identify factors associated with prolonged overall survival (OS).
      PATIENTS AND METHODS: We retrospectively identified 652 metastases in 95 patients
      treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox
      regression analyzed factors predictive for OS. RESULTS: Patients had a median of
      2 metastases (range, 1-14) treated per course, with a median of 2 courses (range,
      2-14) of SRS per patient. With a median follow-up after first SRS of 15 months
      (range, 3-98 months), the median OS from the time of the first and second course
      of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17),
      respectively. On multivariate analysis, histology, graded prognostic assessment
      score, aggregate tumor volume (but not number of metastases), and performance
      status correlated with OS. The 1-year cumulative incidence, with death as a
      competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75
      deaths were from neurologic causes. Nineteen patients (20%) eventually received
      WBRT. Adverse radiation events developed in 2% of SRS sites. CONCLUSION: Multiple
      courses of SRS, deferring WBRT, for distant brain metastases after initial SRS,
      seem to be a safe and effective approach. The graded prognostic assessment score,
      updated at each course, and aggregate tumor volume may help select patients in
      whom the deferral of WBRT might be most beneficial.

PMID- 26194678
TI  - Computed Tomography-Guided Interstitial High-Dose-Rate Brachytherapy in
      Combination With Regional Positive Lymph Node Intensity-Modulated Radiation
      Therapy in Locally Advanced Peripheral Non-Small Cell Lung Cancer: A Phase 1
      Clinical Trial.
AB  - PURPOSE: To assess the technical safety, adverse events, and efficacy of computed
      tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in
      combination with regional positive lymph node intensity modulated radiation
      therapy in patients with locally advanced peripheral non-small cell lung cancer
      (NSCLC). METHODS AND MATERIALS: Twenty-six patients with histologically confirmed
      NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary
      tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to
      the 90% isodose line of the gross lung tumor volume. A total dose of at least 70
      Gy was administered to the 95% isodose line of the planning target volume of
      malignant lymph nodes using 6-MV X-rays. The patients received concurrent or
      sequential chemotherapy. We assessed treatment efficacy, adverse events, and
      radiation toxicity. RESULTS: The median follow-up time was 28 months (range, 7-44
      months). There were 3 cases of mild pneumothorax but no cases of hemothorax,
      dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic
      toxicity was observed in 5 patients. During follow-up, mild fibrosis around the
      puncture point was observed on the CT scans of 2 patients, but both patients were
      asymptomatic. The overall response rates (complete and partial) for the primary
      mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2
      year overall survival (OS) rates were 90.9% and 67%, respectively, with a median
      OS of 22.5 months. CONCLUSION: Our findings suggest that HDR brachytherapy is
      safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2
      clinical trial.

PMID- 26194679
TI  - Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer
      Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in
      Radiation Therapy Planning.
AB  - PURPOSE: Proliferating bone marrow is exquisitely sensitive to ionizing
      radiation. Knowledge of its distribution could improve radiation therapy planning
      to minimize unnecessary marrow exposure and avoid consequential prolonged
      myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)-positron
      emission tomography (PET) is a novel imaging modality that provides detailed
      quantitative images of proliferating tissues, including bone marrow. We used FLT
      PET imaging in cancer patients to produce an atlas of marrow distribution with
      potential clinical utility. METHODS AND MATERIALS: The FLT-PET and fused CT scans
      of eligible patients with non-small cell lung cancer (no distant metastases, no
      prior cytotoxic exposure, no hematologic disorders) were reviewed. The
      proportions of skeletal FLT activity in 10 predefined bony regions were
      determined and compared according to age, sex, and recent smoking status.
      RESULTS: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87)
      years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant
      differences in marrow distribution occurred between sex and age groups. No effect
      was detected from smoking in the preceding 3 months. Using the mean percentages
      of FLT uptake per body region, we created an atlas of the distribution of
      functional bone marrow in 4 subgroups defined by sex and age. CONCLUSIONS: This
      atlas has potential utility for estimating the distribution of active marrow in
      adult cancer patients to guide radiation therapy planning. However, because of
      interindividual variation it should be used with caution when radiation therapy
      risks ablating large proportions of active marrow; in such cases, individual FLT
      PET scans may be required.

PMID- 26194680
TI  - Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation
      Agreement Among NRG Sarcoma Radiation Oncologists.
AB  - PURPOSE: The purpose of this study was to evaluate the variability in target
      volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma
      (RPS) among 12 sarcoma radiation oncologists. METHODS AND MATERIALS: Radiation
      planning computed tomography (CT) scans for 2 cases of RPS were distributed among
      12 sarcoma radiation oncologists with instructions for contouring gross tumor
      volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to
      be at high risk of resulting in positive margins after resection), and OARs:
      bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour
      agreement was performed using the simultaneous truth and performance level
      estimation (STAPLE) algorithm and kappa statistics. RESULTS: Ten radiation
      oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only
      RPS2 such that each case was contoured by 11 radiation oncologists. The first
      case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a
      predominant well-differentiated (WD) component, and the second case (RPS 2) was a
      patient with DD LPS made up almost entirely of a DD component. Contouring
      agreement for GTV and CTV contours was high. However, the agreement for HR CTVs
      was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and
      colon was high, but agreement for duodenum (distorted by tumor in one of these
      cases) was fair to moderate. CONCLUSIONS: For preoperative treatment of RPS,
      sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level
      of agreement. HR CTV contours were more variable. Further clarification of this
      volume with the help of sarcoma surgical oncologists is necessary to reach
      consensus. More attention to delineation of the duodenum is also needed.

PMID- 26194681
TI  - Combined Limb-Sparing Surgery and Radiation Therapy to Treat Sarcomas of the
      Hands and Feet: Long-Term Cancer Outcomes and Morbidity.
AB  - PURPOSE: The purpose of this study was to investigate local control, survival
      outcomes, and complication rates of patients treated with limb-sparing surgery
      and radiation therapy (RT) for soft tissue sarcomas (STS) of the hands and feet.
      METHODS AND MATERIALS: We reviewed the medical records of 85 consecutive patients
      treated for STS of the hands (n=38, 45%) and feet (n=47, 55%) between 1966 and
      2012. The median age was 41 years (range, 10-82 years of age). Sixty-seven
      patients (79%) received postoperative RT after resection of their tumor (median
      dose, 60 Gy; range, 45-70 Gy). The remaining 18 patients (21%) were treated with
      preoperative RT followed by tumor resection (median dose, 50 Gy; range, 50-64
      Gy). RESULTS: Median follow-up was 140 months (range, 24-442 months). Five-year
      local control, overall survival, and disease-specific survival rates were 86%,
      89%, and 89%, respectively. Positive or uncertain surgical margin status was the
      only factor adversely associated with local recurrence (19% vs 6% for negative
      margins, P=.046) but this lost significance on multivariate analysis when
      adjusting for RT dose >=64 Gy. Of the 12 patients who had local relapses, 6 (50%)
      were salvaged, and only 2 of those required salvage amputation. Five patients had
      grade >=3 late RT sequelae, with 2 patients (2%) having moderate limitations of
      limb function and 3 patients (4%) having severe limitations requiring procedures
      for skin ulceration. CONCLUSIONS: Limb-sparing surgery combined with RT provides
      excellent local control outcomes for sarcomas arising in the hands or feet. In
      patients who have local recurrence, salvage without amputation is possible. The
      excellent cancer control outcomes observed, considering the minimal impact on
      limb function, support use of combined modality, limb-sparing local therapy for
      STS arising in the hands or feet.

PMID- 26194682
TI  - Intraoperative Electron-Beam Radiation Therapy for Pediatric Ewing Sarcomas and
      Rhabdomyosarcomas: Long-Term Outcomes.
AB  - PURPOSE: To assess long-term outcomes and toxicity of intraoperative electron
      beam radiation therapy (IOERT) in the management of pediatric patients with Ewing
      sarcomas (EWS) and rhabdomyosarcomas (RMS). METHODS AND MATERIALS: Seventy-one
      sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary
      (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November
      2012. Local control (LC), overall survival (OS), and disease-free survival were
      estimated using Kaplan-Meier methods. For survival outcomes, potential
      associations were assessed in univariate and multivariate analyses using the Cox
      proportional hazards model. RESULTS: After a median follow-up of 72 months
      (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%,
      and 68%, respectively. In multivariate analysis after adjustment for other
      covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and
      P=.04) remained significantly associated with LC and OS. Nine patients (13%)
      reported severe chronic toxicity events (all grade 3). CONCLUSIONS: A multimodal
      IOERT-containing approach is a well-tolerated component of treatment for
      pediatric EWS and RMS patients, allowing reduction or substitution of external
      beam radiation exposure while maintaining high local control rates.

PMID- 26194683
TI  - Inverse Planned High-Dose-Rate Brachytherapy for Locoregionally Advanced Cervical
      Cancer: 4-Year Outcomes.
AB  - PURPOSE: Evaluate the efficacy and toxicity of image guided brachytherapy using
      inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB)
      boost for locoregionally advanced cervical cancer. METHODS AND MATERIALS: From
      December 2003 through September 2009, 111 patients with primary cervical cancer
      were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions)
      after external radiation at our institution. We performed a retrospective review
      of our experience using image guided brachytherapy. Of the patients, 70% had a
      tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident
      distant metastasis, including nonregional nodal disease, at the time of
      diagnosis. Surgical staging involving pelvic lymph node dissection was performed
      in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy.
      Toxicities are reported according to the Common Terminology Criteria for Adverse
      Events version 4.0 guidelines. RESULTS: With a median follow-up time of 42 months
      (range, 3-84 months), no acute or late toxicities of grade 4 or higher were
      observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1
      constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year
      Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed
      in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72
      months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost).
      The 4-year estimates of local, locoregional, and distant control of disease were
      94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival
      rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0%
      (95% CI, 51%-70%), respectively. CONCLUSIONS: Definitive radiation by use of
      inverse planned HDRB boost for locoregionally advanced cervical cancer is well
      tolerated and achieves excellent local control of disease. However, overall
      survival continues to be limited by the high rates of distant metastasis.

PMID- 26194684
TI  - Multileaf Collimator Tracking Improves Dose Delivery for Prostate Cancer
      Radiation Therapy: Results of the First Clinical Trial.
AB  - PURPOSE: To test the hypothesis that multileaf collimator (MLC) tracking improves
      the consistency between the planned and delivered dose compared with the dose
      without MLC tracking, in the setting of a prostate cancer volumetric modulated
      arc therapy trial. METHODS AND MATERIALS: Multileaf collimator tracking was
      implemented for 15 patients in a prostate cancer radiation therapy trial; in
      total, 513 treatment fractions were delivered. During each treatment fraction,
      the prostate trajectory and treatment MLC positions were collected. These data
      were used as input for dose reconstruction (multiple isocenter shift method) to
      calculate the treated dose (with MLC tracking) and the dose that would have been
      delivered had MLC tracking not been applied (without MLC tracking). The
      percentage difference from planned for target and normal tissue dose-volume
      points were calculated. The hypothesis was tested for each dose-volume value via
      analysis of variance using the F test. RESULTS: Of the 513 fractions delivered,
      475 (93%) were suitable for analysis. The mean difference and standard deviation
      between the planned and treated MLC tracking doses and the planned and without
      MLC tracking doses for all 475 fractions were, respectively, PTV D99% -0.8% +/-
      1.1% versus -2.1% +/- 2.7%; CTV D99% -0.6% +/- 0.8% versus -0.6% +/- 1.1%; rectum
      V65% 1.6% +/- 7.9% versus -1.2% +/- 18%; and bladder V65% 0.5% +/- 4.4% versus 
      0.0% +/- 9.2% (P<.001 for all dose-volume results). CONCLUSION: This study shows
      that MLC tracking improves the consistency between the planned and delivered
      doses compared with the modeled doses without MLC tracking. The implications of
      this finding are potentially improved patient outcomes, as well as more reliable
      dose-volume data for radiobiological parameter determination.

PMID- 26194686
TI  - Erratum to: Mathilda L. Bongers, Veerle M.H. Coupe, Dirk De Ruysscher, Cary
      Oberije, Philippe Lambin, and Cornelia A. Uyl-de Groot. Individualized Positron
      Emission Tomography-Based Isotoxic Accelerated Radiation Therapy Is Cost
      Effective Compared With Conventional Radiation Therapy: A Model-Based Evaluation.
      Int J Radiat Oncol Biol Phys 2015;91:857-865.

PMID- 26194685
TI  - Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck
      Cancer Patients Based on Individual and Subgroup Normal Tissue Complication
      Probability Analysis.
AB  - PURPOSE: The purpose of this study was to determine, by treatment plan comparison
      along with normal tissue complication probability (NTCP) modeling, whether a
      subpopulation of patients with head and neck squamous cell carcinoma (HNSCC)
      could be identified that would gain substantial benefit from proton therapy in
      terms of NTCP. METHODS AND MATERIALS: For 45 HNSCC patients, intensity modulated
      radiation therapy (IMRT) was compared to intensity modulated proton therapy
      (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP
      values, using modern models for acute mucositis, xerostomia, aspiration,
      dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on
      primary tumor location. RESULTS: Generally, IMPT reduced the NTCP values while
      keeping similar target coverage for all patients. Subgroup analyses revealed a
      higher individual reduction of swallowing-related side effects by IMPT for
      patients with tumors in the upper head and neck area, whereas the risk reduction
      of acute mucositis was more pronounced in patients with tumors in the larynx
      region. More patients with tumors in the upper head and neck area had a reduction
      in NTCP of more than 10%. CONCLUSIONS: Subgrouping can help to identify patients
      who may benefit more than others from the use of IMPT and, thus, can be a useful
      tool for a preselection of patients in the clinic where there are limited PT
      resources. Because the individual benefit differs within a subgroup, the relative
      merits should additionally be evaluated by individual treatment plan comparisons.

PMID- 26194689
TI  - [Dr. Elisa Einwallner, PhD is Researcher of the Month, July2015].

PMID- 26194690
TI  - The development of a prototype measure of the co-production of health in routine
      consultations for people with long-term conditions.
AB  - OBJECTIVES: (i) To develop a prototype measure of co-production of health (CPH)
      in consultations for people with long-term conditions (LTCs); and (ii) to
      undertake initial validation of it, using a measure of patient-centred care, as
      defined by the Roter interaction analysis system (RIAS). METHODS: Mixed methods
      were applied. A qualitative study gathered 11 experts' views on what comprised
      CPH behaviours. These were operationalised and a prototype measure applied to a
      convenience sample of 50 video-recorded consultations involving clinicians
      trained in self-management support and patients with LTCs at health services in
      six UK locations. RESULTS: Twenty-two CPH behaviours were identified. High
      frequencies of CPH behaviours in consultations were associated with greater
      patient-centeredness, less clinician verbal dominance, and more patient
      communication control in comparison to consultations where CPH behaviours were
      less frequent. CONCLUSION: Although the CPH tool is promising, further testing is
      required in order to improve reliability and validity. PRACTICAL IMPLICATIONS: In
      the future, the measure could be used to test interventions to promote patient
      participation in decision making about self-management.

PMID- 26194691
TI  - Increased thrombin generation in women with polycystic ovary syndrome: A pilot
      study on the effect of metformin and oral contraceptives.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with risk factors for
      cardiovascular disease (CVD) which may be modified by the use of metformin and
      oral contraceptives (OC). Thrombin generation (TG) measures are risk markers of
      CVD and address the composite of multiple factors that influence blood
      coagulation. This prospective, randomized, intervention study evaluated the
      potential influence of PCOS on TG measures and the effect of OC and/or metformin
      on TG measures in women with PCOS. MATERIAL AND METHODS: Ninety patients with
      PCOS and 35 controls were included. Patients were randomized to 12 months of
      treatment with metformin, metformin+OC or OC alone. C-reactive protein (CRP),
      fibrinogen, total cholesterol, trunk fat mass, body mass index, estradiol,
      testosterone, sex hormone binding globulin (SHBG) as well as TG measures, i.e.
      the lag time for formation of thrombin, the endogenous thrombin potential (ETP),
      peak thrombin concentration (peak) and time to peak were determined at baseline
      and after 12 months of treatment. RESULTS: CRP and total testosterone were
      significantly higher and SHBG significantly lower in PCOS women than in controls
      (P=0.012, P<0.001 and P=0.008, respectively). The TG measures ETP, peak and lag
      time were increased in women with PCOS compared to controls (P<0.01). Significant
      correlations were observed between TG measures and fibrinogen, CRP, SHBG and fat
      trunk mass (P>0.01). ETP (P=0.006), peak (P=0.003) and lag time (P=0.023)
      remained increased after adjustment for these potential confounders. Treatment
      with OC and metformin+OC further increased ETP (P<0.001) and peak (P<0.005) and
      reduced time to peak (P<0.04). The increase in ETP was significantly lower in the
      metformin+OC group than in the OC group (P<0.05). Metformin alone did not affect
      TG significantly. CONCLUSIONS: PCOS is associated with increase in TG measures
      independent of other risk factors of CVD. OC increase TG measures further and may
      thus add to the increased risk of CVD already present in women with PCOS.

PMID- 26194692
TI  - Environmental survival of vancomycin-sensitive ampicillin-resistant Enterococcus
      faecium (AREfm).
AB  - Ampicillin-resistant Enterococcus faecium (AREfm) has gained increased footholds
      in many hospital intensive care units (ICUs) and belongs to specific hospital
      adapted E. faecium sub-populations. Three AREfm strains survived in an in vitro
      survival setting for approximately 5.5 years. These findings have important
      consequences for the epidemiology of AREfm in hospital settings and stress the
      importance of maintaining a good level of hospital hygiene. 

PMID- 26194693
TI  - Polymorphisms in host genes encoding NOSII, C-reactive protein, and adhesion
      molecules thrombospondin and E-selectin are risk factors for Plasmodium
      falciparum malaria in India.
AB  - Cytoadherence of Plasmodium falciparum-infected red blood cells (RBCs) in host
      microvasculature and complex regulation of the immune response are important
      contributors to the clinical outcome of disease. We tested the association of 23
      single nucleotide polymorphisms (SNPs) and a microsatellite repeat in adhesion
      molecule genes THBS1 and ESEL, and immune regulatory molecule genes NOSII, CRP,
      and MBL2 with falciparum malaria in populations residing in a malaria-endemic and
      a non-endemic region of India. The THBS1 haplotype CCCCA (rs1478604, rs7170682,
      rs2664141, rs12912082, rs3743125) was a risk factor in the endemic region
      (relative risk = 3.78) and an ESEL SNP (rs5368, His468Tyr) associated with
      cerebral malaria (CM) [CM vs. non-cerebral malaria (NCM), odds ratio (OR) = 2.23,
      p = 0.03]. In the non-endemic region, an ESEL 3'UTR SNP (rs5359) associated with
      enhanced risk of disease (OR = 3.62, p = 1 * 10(-4)) and the CT genotype of the
      CRP promoter SNP (C/T/A) strongly associated with protection (severe vs. control,
      OR = 0.29, p = 6 * 10(-5)). Long repeat alleles of the NOSII promoter
      microsatellite (CCTTT)n exhibited strong association with protection and the
      NOSII ATG haplotype (rs3729508, rs2297520, rs9282801) was strongly protective
      against severe malaria in both regions (endemic, severe vs. control, OR = 0.05, p
      = 0.0001; non-endemic, severe vs. control, OR = 0.3, p = 1 * 10(-5)). Our results
      suggest differential contribution of variants of the investigated genes in
      determining the outcome of malaria in Indian populations.

PMID- 26194694
TI  - In vitro antimicrobial susceptibility of Helcococcus kunzii and molecular
      analysis of macrolide and tetracycline resistance.
AB  - Thanks to the recent advent of matrix-assisted laser desorption/ionisation time
      of-flight (MALDI-TOF) technology, Helcococcus kunzii is now easily identifiable
      and considered as an opportunistic pathogen. However, data about antimicrobial
      susceptibilities remain very limited. The aim of the study was, then, to assess
      its in vitro susceptibility to 18 antimicrobial agents and to investigate the
      genetic basis of macrolide and tetracycline resistance. Thirty-nine human
      clinical isolates of H. kunzii collected from 2008 to 2013 were studied, as well
      as the type strain ATCC 51366(T). Minimum inhibitory concentrations (MICs) of
      penicillin G, amoxicillin, cefotaxime, imipenem, gentamicin, erythromycin,
      clindamycin, quinupristin-dalfopristin, ciprofloxacin, levofloxacin,
      tetracycline, tigecycline, vancomycin, teicoplanin, linezolid, daptomycin,
      cotrimoxazole and rifampin were determined by the microdilution method. Screening
      for macrolide [erm(A) including erm(TR), erm(B), erm(C), erm(F), erm(T), erm(X),
      msr(A) and mef(A)] and tetracycline [tet(L), tet(M) and tet(O)] resistance genes
      was performed, as well as the detection of mutations in 23S rRNA. Except for one
      strain resistant to cefotaxime, all strains were categorised as susceptible to
      beta-lactams, glycopeptides, linezolid, daptomycin and tigecycline. Whereas
      ciprofloxacin and gentamicin exhibited limited activity, 95% of strains were
      categorised as susceptible to levofloxacin. Concerning erythromycin, a bimodal
      distribution was observed, with 29 'wild-type' strains (MICs from 0.25 to 2 mg/L)
      and 11 'resistant' strains (MICs >= 256 mg/L), including ten harbouring erm(TR).
      Two isolates exhibited acquired tetracycline resistance (MICs of 16 mg/L) by the
      production of tet(M). This large study on the in vitro antimicrobial
      susceptibility of H. kunzii suggests that beta-lactams (especially penicillins)
      should be preferred for the treatment.

PMID- 26194695
TI  - ERBB3 is required for tumor promotion in a mouse model of skin carcinogenesis.
AB  - The epidermal growth factor receptor (EGFR) plays a key role in skin
      inflammation, wound healing, and carcinogenesis. Less is known about the
      functions of the structurally related receptor ERBB3 (HER3) in the skin. We
      assessed the requirement of ERBB3 for skin homeostasis, wound healing, and
      tumorigenesis by crossing mice carrying a conditional Erbb3 allele with animals
      expressing cre under the control of the keratin 5 promoter. Erbb3(del) mice,
      lacking ERBB3 specifically in keratinocytes, showed no obvious abnormalities. The
      EGFR was upregulated in Erbb3(del) skin, possibly compensating the loss of ERBB3.
      Nonetheless, healing of full-thickness excisional wounds was negatively affected
      by ERBB3 deficiency. To analyze the function of ERBB3 during tumorigenesis, we
      employed the established DMBA/TPA multi-stage chemical carcinogenesis protocol.
      Erbb3(del) mice remained free of papillomas for a longer time and had
      significantly reduced tumor burden compared to control littermates. Tumor cell
      proliferation was considerably reduced in Erbb3(del) mice, and loss of ERBB3 also
      impaired keratinocyte proliferation after a single application of TPA. In human
      skin tumor samples, upregulated ERBB3 expression was observed in squamous cell
      carcinoma, condyloma, and malignant melanoma. Thus, we conclude that ERBB3, while
      dispensable for the development and the homeostasis of the epidermis and its
      appendages, is required for proper wound healing and for the progression of skin
      tumors during multi-stage chemical carcinogenesis in mice. ERBB3 may also be
      important for human skin cancer progression. The latter effects most probably
      reflect a key role for ERBB3 in increasing cell proliferation after stimuli as
      wounding or carcinogenesis. 

PMID- 26194696
TI  - A simple and efficient method to transfect small interference RNA into bovine
      SCNT embryos.
AB  - RNA interference is an important tool to study the gene function. Microinjection
      and electroporation are usually used to transfer DNA, small interference RNA
      (siRNA), morpholinos, and protein into oocytes or embryos. This study used a
      simple and effective method to transfect siRNA into bovine somatic cell nuclear
      transfer (SCNT) embryos. In this method, siRNA transfection and electrofusion of
      SCNT were combined. A pair of platinum microelectrodes was used during SCNT to
      complete electrofusion. A CY3-labeled siRNA-targeted DNA methyltransferase-1
      (DNMT1) was chosen to verify the siRNA transfection efficiency of this approach.
      First, a suitable concentration of siRNA was mixed with Zimmermann's fusion
      medium. Reconstructed embryos were then added into the microdrops of the mixed
      fusion medium to simultaneously transfect the siRNA and electrofuse the SCNT
      embryos. Our results showed that transfecting DNMT1 siRNA via the proposed method
      caused obvious CY3 fluorescence and significant downregulation of DNMT1 messenger
      RNA, DNMT1 protein, and global DNA methylation levels in the SCNT embryos.
      Meanwhile, the survival rate after electrofusion (90.4% vs. 89.4% vs. 89.1%, P >
      0.05) and developmental rates of the SCNT embryos (72.8% vs. 74.9% vs. 72.4%, P >
      0.05; 29.7% vs. 31.7% vs. 29.7%, P > 0.05) were not significantly affected. In
      summary, siRNAs were effectively transfected into the SCNT embryos via the
      proposed method and exert their functions, and the normal development of
      preimplantation SCNT embryos was not affected by the method used.

PMID- 26194697
TI  - Ultrasonographic and progesterone changes during Days 21 to 63 of pregnancy in
      queens.
AB  - Ultrasonography has been used to diagnose and monitor pregnancy. However, in the
      queen, most of ultrasonographic and endocrinological studies have been performed
      using small number of observations during limited periods of pregnancy. The aim
      of this study was to derive equations to predict the gestation age and
      parturition time using ultrasonographic embryo fetus measurements and serum
      progesterone (P4) concentration measurements. Mixed-breed queens (n = 16), aged
      between 24 and 36 months and weighing between 2 and 4 kg, were daily monitored by
      ultrasonography since 21 days after the first mating to parturition. Gestational
      sac (GS) was measured from longitudinal (length [LEN], anterior-posterior [ATP])
      and transverse images (width [WID]), GS volume was calculated by the prolate
      ellipse formula, and GS diameter was calculated by orthogonal measurements. Fetal
      measurements included crown-rump length (CRL), head diameter (HD), and body
      diameter (BD). Gestational sac, fetal measurements, and serum P4 concentration
      were recorded and analyzed by ANOVA. Correlation and linear regression analyses
      were performed and equations were derived to estimate predicted values and 95%
      confidence interval for GS parameters and P4 concentrations from 21 to 63 days
      after the first mating and to estimate predicted values and 95% confidence
      interval for fetal parameters from Day 35 to 63 of gestation. The average
      concentrations of serum P4 concentration from Day 22 to 47 of gestation remained
      between 32.27 +/- 4.25 and 16.25 +/- 2.45 ng/mL. After that, a gradual decline
      occurs reaching a concentration of 2.99 +/- 1.29 ng/mL 1 day before parturition.
      A positive and significant correlation between the ultrasonographic measurements
      (LEN, ATP, WID, GS volume and diameter, uterine wall thickness, CRL, HD, and BD)
      with number of days after the first mating was observed (P < 0.001). We observed
      a positive and significant correlation between GS measurements (LEN, ATP, and
      WID) and between fetal measurements (CRL, HD, and BD) and a negative and
      significant correlation between serum P4 concentration with GS (LEN, ATP, and
      WID), uterine wall thickness, and fetal (CRL, HD, and BD) measurements. In
      addition, there was a positive and significant correlation between serum P4
      concentrations with days after the first mating to parturition. In conclusion,
      the equations derived from this study will be useful for pregnancy monitoring and
      for estimating pregnancy age in queens from Day 21 until parturition for animals
      with similar weight and age.

PMID- 26194698
TI  - The effects of human recombinant granulocyte-colony stimulating factor treatment
      during in vitro maturation of porcine oocyte on subsequent embryonic development.
AB  - Granulocyte colony-stimulating factor (G-CSF) is required for proliferation,
      differentiation, and survival of cells. It is also a biomarker of human oocyte
      developmental competence for embryo implantation. In humans, the G-CSF
      concentration peaks during the ovulatory phase of the ovarian cycle. In this
      study, the expressions of G-CSF and its receptor were analyzed by polymerase
      chain reaction in granulosa cells (GCs), CL, cumulus cells (CCs), and oocytes.
      Cumulus-oocyte complexes were aspirated from antral follicles of 1 to 3 mm (small
      follicles) and 4 to 6 mm (medium follicles). Cumulus-oocyte complexes from two
      kinds of follicles were matured in protein-free maturation medium supplemented
      with various concentrations of G-CSF (0, 10, and 100 ng/mL). By real-time
      polymerase chain reaction, the expressions of G-CSF and its receptor were
      detected in GCs, CL, CCs, and oocytes. Interestingly, the G-CSF transcript levels
      were significantly lower in oocytes than in the other cell types, whereas the G
      CSF receptor transcript levels in oocytes were similar to those in GCs. After 44
      hours of IVM, no differences in the rate of nuclear maturation were detected;
      however, the intracellular reactive oxygen species levels in oocytes from both
      groups of follicles matured with 10 ng/mL of human recombinant G-CSF (hrG-CSF)
      groups were significantly lower (P < 0.05). After parthenogenetic activation, the
      cleavage rates were significantly (P < 0.05) higher in 100 ng/mL hrG-CSF-treated
      small (63.3%) follicles than in 0, 10 ng/mL hrG-CSF-treated small (38.6% and
      49.0%, respectively) follicles and 0 ng/mL hrG-CSF-treated medium (52.1%)
      follicles, and the cleavage rates were significantly (P < 0.05) higher in 10
      ng/mL hrG-CSF-treated medium (76.3%) follicles than in all other groups. The
      blastocyst formation rates were significantly (P < 0.05) higher in 100 ng/mL hrG
      CSF-treated small (31.2%) follicles than in 0 and 10 ng/mL hrG-CSF small (10.4%
      and 15.6%, respectively) follicles, and the 10 ng/mL hrG-CSF medium (45.7%)
      follicle was significantly (P < 0.05) higher than in all other groups. The total
      cell number in blastocysts from the 10 ng/mL hrG-CSF medium (106.5) follicles was
      significantly (P < 0.05) increased compared to 0, 10, 100 ng/mL hrG-CSF small
      (55.0, 73.7 and 59.5, respectively) follicles and 0, 100 ng/mL hrG-CSF-treated
      medium (82.5 and 93.5, respectively) follicles. After IVF, the blastocysts stage
      was significantly (P < 0.05) increased in 10 ng/mL hrG-CSF-treated medium (36.4%)
      follicles. Fertilization efficiency was significantly high in 100 ng/mL of small
      (29.1%) and 10 ng/mL of medium (44.0%) follicles. We also examined the Bcl2 and
      ERK2 transcript levels and found that they were significantly higher in the small
      and medium follicle treatment groups. In conclusion, these results indicate that
      hrG-CSF improve the viability of porcine embryos.

PMID- 26194699
TI  - Effect of age and endometrial degenerative changes on uterine blood flow during
      early gestation in mares.
AB  - The present experiment was divided into three studies to investigate the effect
      of age and endometrial degeneration on uterine blood flow of mares. In study 1,
      the influence of semen infusion and conception was evaluated using noninseminated
      (non-AI), inseminated nonpregnant (AI-NP), and inseminated pregnant (AI-P) mares
      (n = 7 mares/group). In study 2, the effect of age was investigated using young
      (<=6 years), adult (from 8 to 12 years), and old (>=15 years) pregnant mares (n =
      7 mares/group). In study 3, uterine blood flow was also characterized in pregnant
      mares (n = 7 mares/group) with minimal, moderate, or severe endometrial
      degenerative changes (GI, GII, and GIII, respectively). Uterine vascular
      perfusion and pulsatility index from mesometrium attachment arteries were
      recorded daily from Day 0 (day of ovulation) to Day 12 and between Days 0 and 20
      in nonpregnant and pregnant mares. Analysis according to the position of the
      embryo (uterine horn with embryo vs. opposite horn) was performed from Day 12
      until Day 20. In study 1, increased uterine vascular perfusion and decreased
      pulsatility index were detected (P < 0.001) between Days 3 and 5 in non-AI and AI
      P mares, whereas the uterine vascular perfusion of AI-NP mares did not change (P
      > 0.05) throughout the experiment. In study 2, the vascular perfusion of the
      uterine horn with embryo was higher (P < 0.001) than in the opposite uterine horn
      from Day 12 until Day 20 in both young and adult mares. With exception of Day 15,
      both uterine horns of old mares showed similar (P > 0.1) vascular perfusion from
      Day 12. In study 3, vascular perfusion of both uterine horns was lower (P <
      0.001) in GIII mares than in GI and GII mares. After Day 15, the scores for
      uterine vascular perfusion were consistently greater (P < 0.001) in the uterine
      horn with embryo than in the opposite horn in GI mares. Results showed, for the
      first time, the reduced blood flow of the gravid uterus during early gestation in
      older mares and in mares with significant endometrial degeneration.

PMID- 26194700
TI  - Protein kinase C in the immune system: from signalling to chromatin regulation.
AB  - Protein kinase C (PKC) form a key family of enzymes involved in signalling
      pathways that specifically phosphorylates substrates at serine/threonine
      residues. Phosphorylation by PKC is important in regulating a variety of cellular
      events such as cell proliferation and the regulation of gene expression. In the
      immune system, PKCs are involved in regulating signal transduction pathways
      important for both innate and adaptive immunity, ultimately resulting in the
      expression of key immune genes. PKCs act as mediators during immune cell
      signalling through the immunological synapse. PKCs are traditionally known to be
      cytoplasmic signal transducers and are well embedded in the signalling pathways
      of cells to mediate the cells' response to a stimulus from the plasma membrane to
      the nucleus. PKCs are also found to transduce signals within the nucleus, a
      process that is distinct from the cytoplasmic signalling pathway. There is now
      growing evidence suggesting that PKC can directly regulate gene expression
      programmes through a non-traditional role as nuclear kinases. In this review, we
      will focus on the role of PKCs as key cytoplasmic signal transducers in immune
      cell signalling, as well as its role in nuclear signal transduction. We will also
      highlight recent evidence for its newly discovered regulatory role in the nucleus
      as a chromatin-associated kinase. 

PMID- 26194705
TI  - Genital involvement in pemphigus vulgaris (PV): correlation with clinical and
      cervicovaginal Pap smear findings.
AB  - BACKGROUND: The frequency of genital involvement in pemphigus vulgaris (PV) has
      not been clearly defined. OBJECTIVES: We sought to evaluate the frequency of
      cervical, vaginal, and vulvar involvement in PV and to determine their
      association with genital symptoms, clinical involvement, and cytological status.
      METHODS: The current study's sample included 34 female patients with PV.
      Gynecologic and ear, nose, and throat examinations and indirect
      immunofluorescence analyses were performed, and Pap smears were collected.
      RESULTS: Genital involvement was observed in 44.1% of patients. It was
      significantly associated with disease severity and clinical involvement.
      Pharyngeal involvement was observed in 61.8% of patients and was the second-most
      frequently involved mucosal region. Genital involvement was significantly
      associated with nasal mucosa involvement. Cervicovaginal Pap smears showed
      acantholytic cells of PV in 35.3% of patients. LIMITATION: The sample size is
      small. CONCLUSION: Genital involvement in PV is not rare. Genital mucosa is the
      most affected mucosal region after oral and pharyngeal mucosa. Furthermore,
      genital involvement is significantly associated with nasal involvement and
      genital symptoms. The need for complete gynecologic evaluations of patients with
      PV, nasal involvement, and genital symptoms is emphasized.

PMID- 26194706
TI  - Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor
      tofacitinib citrate.
AB  - BACKGROUND: Treatment of moderate to severe atopic dermatitis (AD) is often
      inadequate. OBJECTIVE: We sought to evaluate the efficacy of the oral Janus
      kinase inhibitor tofacitinib citrate in the treatment of moderate to severe AD.
      METHODS: Six consecutive patients with moderate to severe AD who had failed
      standard treatment were treated with tofacitinib citrate. Response to treatment
      was assessed using the Scoring of AD index. RESULTS: Decreased body surface area
      involvement of dermatitis and decreased erythema, edema/papulation,
      lichenification, and excoriation were observed in all patients. The Scoring of AD
      index decreased by 66.6% from 36.5 to 12.2 (P < .05) during 8 to 29 weeks of
      treatment. There were no adverse events. LIMITATIONS: Small sample size, lack of
      placebo control group, and the possibility of bias are limitations. CONCLUSION:
      The oral Janus kinase inhibitor tofacitinib citrate may be beneficial in the
      treatment of moderate to severe AD.

PMID- 26194707
TI  - De Novo Assembly of Plasmids Using Yeast Recombinational Cloning.
AB  - Molecular cloning is a cornerstone of modern biology laboratories. However,
      traditional cloning can be time-consuming and problematic. We outline herein a
      method that utilizes the endogenous gap repair system of yeast cells to clone and
      assemble DNA constructs. This system is simple, cheap, and requires minimal
      reagents. It can be used for the assembly of both simple (single DNA fragments)
      and complex (multiple DNA fragments) constructs into plasmids. 

PMID- 26194708
TI  - Conjugative Transfer in Staphylococcus aureus.
AB  - The acquisition of plasmids has led to a significant increase in antimicrobial
      resistance within the staphylococci. In order to study these plasmids
      effectively, one must be able move the plasmid DNA into genetically clean
      backgrounds. While the smaller staphylococcal class I (1-5 kb) and class II (10
      30 kb) plasmids are readily transferred using bacteriophage transduction or
      electroporation, these methods are inefficient at moving the larger class III (30
      60 kb) plasmids. This review describes methods to transfer class III plasmids via
      conjugative mobilization.

PMID- 26194709
TI  - Electrophoretic Mobility Shift Assays.
AB  - Experimental demonstration of regulatory protein interactions with the sequences
      upstream of potential target genes is an important element in gene expression
      studies. These experiments termed electrophoretic mobility shift assays (EMSAs)
      provide valuable insight into the mechanism of action of transcription factors.
      EMSAs combined with downstream applications such as transcriptional analysis help
      uncover precisely how regulatory proteins control target gene expression. This
      chapter comprises a guideline for expression and purification of recombinant
      transcription factor proteins followed by a detailed protocol for EMSAs.

PMID- 26194704
TI  - Expert consensus document: European Consensus Statement on congenital
      hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment.
AB  - Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the
      deficient production, secretion or action of gonadotropin-releasing hormone
      (GnRH), which is the master hormone regulating the reproductive axis. CHH is
      clinically and genetically heterogeneous, with >25 different causal genes
      identified to date. Clinically, the disorder is characterized by an absence of
      puberty and infertility. The association of CHH with a defective sense of smell
      (anosmia or hyposmia), which is found in ~50% of patients with CHH is termed
      Kallmann syndrome and results from incomplete embryonic migration of GnRH
      synthesizing neurons. CHH can be challenging to diagnose, particularly when
      attempting to differentiate it from constitutional delay of puberty. A timely
      diagnosis and treatment to induce puberty can be beneficial for sexual, bone and
      metabolic health, and might help minimize some of the psychological effects of
      CHH. In most cases, fertility can be induced using specialized treatment regimens
      and several predictors of outcome have been identified. Patients typically
      require lifelong treatment, yet ~10-20% of patients exhibit a spontaneous
      recovery of reproductive function. This Consensus Statement summarizes approaches
      for the diagnosis and treatment of CHH and discusses important unanswered
      questions in the field. 

PMID- 26194710
TI  - Batch Transduction of Transposon Mutant Libraries for Rapid Phenotype Screening
      in Staphylococcus.
AB  - In the gram-positive pathogen Staphylococcus aureus, transposon mutagenesis is a
      useful method of screening large numbers of mutants for a given phenotype.
      However, constructing a transposon mutant library can take several months of work
      and validation in the laboratory. In this chapter, we describe a method for batch
      transduction of existing transposon mutations into new genetic backgrounds.
      Transduction in S. aureus is accomplished quickly and easily in most commonly
      used laboratory strains. The method described herein utilizes transduction to
      facilitate the rapid creation of new libraries and quick screening in strains
      containing phenotypic reporter constructs. 

PMID- 26194711
TI  - Understanding Staphylococcal Nomenclature.
AB  - Bacteria are often grouped by a variety of properties, including biochemical
      activity, appearance, and more recently, nucleic acid sequence differences. In
      the case of human pathogens, significant work goes into "typing" strains to
      understand relatedness. This is especially true when trying to understand the
      epidemiology of these organisms. In attempts to group Staphylococci, a variety of
      methods and nomenclatures have been employed, which can often serve as a point of
      confusion to those entering the field. Therefore, the intent of this chapter is
      to give a brief overview of some common methods and associated nomenclature used
      to type Staphylococci, with S. aureus as an example. 

PMID- 26194712
TI  - Two Novel Algicidal Isolates Kill Chlorella pyrenoidosa by Inhibiting their Host
      Antioxidase Activities.
AB  - In the biocontrol of harmful algal blooms, there has been considerable interest
      about the role of algicidal bacteria in algicidal activity. In this experiment,
      two novel algicidal bacteria (strains NP23 and AM11) against Chlorella
      pyrenoidosa were isolated from the Baiguishan reservoir in China. Phylogenetic
      analysis based on 16S rRNA gene sequences revealed that strains NP23 and AM11
      belonged to Enterobacter cloacae and Gibberella moniliformis, respectively. To
      further understand the algicidal activities, five parameters including the
      chlorophyll a content, cell survival rate, superoxide dismutase (SOD) peroxide
      dismutase (POD), and catalase (CAT) were tested in the C. pyrenoidosa cells after
      inoculation with the algicidal bacteria Enterobacter cloacae NP23 and Gibberella
      moniliformis AM11. As a result, the growth of the treated C. pyrenoidosa was
      significantly restrained with a great decline of chlorophyll a content.
      Meanwhile, three antioxidase activities of the treated C. pyrenoidosa were
      initially stimulated from day 1 to day 3 but then dramatically inhibited at low
      level. These results induced that the oxidative imbalance (i.e., inhibition of
      antioxidase activities) caused by algicidal bacteria could be the killing agent
      of the C. pyrenoidosa cells.

PMID- 26194713
TI  - PET-based compartmental modeling of (124)I-A33 antibody: quantitative
      characterization of patient-specific tumor targeting in colorectal cancer.
AB  - PURPOSE: The molecular specificity of monoclonal antibodies (mAbs) directed
      against tumor antigens has proven effective for targeted therapy of human
      cancers, as shown by a growing list of successful antibody-based drug products.
      We describe a novel, nonlinear compartmental model using PET-derived data to
      determine the "best-fit" parameters and model-derived quantities for optimizing
      biodistribution of intravenously injected (124)I-labeled antitumor antibodies.
      METHODS: As an example of this paradigm, quantitative image and kinetic analyses
      of anti-A33 humanized mAb (also known as "A33") were performed in 11 colorectal
      cancer patients. Serial whole-body PET scans of (124)I-labeled A33 and blood
      samples were acquired and the resulting tissue time-activity data for each
      patient were fit to a nonlinear compartmental model using the SAAM II computer
      code. RESULTS: Excellent agreement was observed between fitted and measured
      parameters of tumor uptake, "off-target" uptake in bowel mucosa, blood clearance,
      tumor antigen levels, and percent antigen occupancy. CONCLUSION: This approach
      should be generally applicable to antibody-antigen systems in human tumors for
      which the masses of antigen-expressing tumor and of normal tissues can be
      estimated and for which antibody kinetics can be measured with PET. Ultimately,
      based on each patient's resulting "best-fit" nonlinear model, a patient-specific
      optimum mAb dose (in micromoles, for example) may be derived.

PMID- 26194714
TI  - Survival outcomes in patients with cervical cancer after inclusion of PET/CT in
      staging procedures.
AB  - PURPOSE: In cancer of the uterine cervix, lymph node metastases are associated
      with a poor prognosis. Even so, the International Federation of Gynecology and
      Obstetrics (FIGO) does not take into account diagnostic results of methods such
      as PET/CT, since these are not readily available everywhere. As undetected lymph
      node metastases can lead to undertreatment, any difference in the underlying
      prevalence of false-negative scans between CT and PET/CT may be reflected in
      treatment outcomes. This study investigated survival outcomes in node-negative
      patients before and after the introduction of PET/CT. METHODS: This was a single
      institution retrospective analysis of 301 patients with a histopathological
      diagnosis of cervical cancer. The patients were receiving chemoradiotherapy with
      curative intent according to the standard protocol of the department for patients
      without lymph node metastases as assessed by pretreatment CT or PET/CT. Patients
      were stratified into two groups: PET/CT and non-PET/CT. Patient characteristics
      and treatment outcomes were acquired from the treatment database. RESULTS:
      Significant differences of 23 % (95 % CI 17 - 29 %), 19 % (95 % CI 13 - 25 %) and
      12 % (95 % CI 6 - 18 %) in 5-year overall, disease-free and disease-specific
      survival, respectively, were observed between the two patient groups. The
      difference remained significant in univariate and multivariate analyses of
      overall survival (hazard ratio 0.61, 95 % CI 0.42 - 0.89; p = 0.010), including
      age, FIGO stage, performance status, BMI, and histopathology. CONCLUSION:
      Inclusion of PET/CT in the preradiotherapy diagnostic protocol may lead to nodal
      stage migration not reflected in the FIGO stage. It was found to be a significant
      covariate, and could lead to selection bias that needs to be taken into account
      when designing and reporting on clinical trials.

PMID- 26194715
TI  - Gastric injury from (90)Y to left hepatic lobe tumors adjacent to the stomach:
      fact or fiction?
AB  - PURPOSE: Radioembolization with (90)Y microspheres is a locoregional radiation
      therapy for unresectable hepatic neoplasm. Non-target delivery of (90)Y
      microspheres resulting in gastrointestinal (GI) symptoms is a recognized
      complication; there is minimal knowledge regarding the radiation effect to the
      gastric wall from left hepatic lobe (90)Y treatments. Our aim was to study the
      incidence of GI complications when the target tissue (hepatic parenchyma +/-
      tumor) is in close proximity to the gastric wall. We hypothesized that liver
      (tumor) to stomach proximity does not correlate with increased toxicity. METHODS:
      Between November 2011 and September 2013, we studied all patients who underwent
      left lobe radioembolization with (90)Y glass microspheres. With Institutional
      Review Board (IRB) approval, we retrospectively reviewed MRI/CT images of these
      patients, identifying a subset of patients with the left hepatic lobe <1 cm from
      the gastric wall. Patients were seen in clinic 1 month posttreatment and
      subsequently at 3-month intervals. Short- and long-term gastric adverse events
      were tabulated. RESULTS: Ninety-seven patients successfully underwent left
      hepatic lobe (90)Y microsphere radioembolization in which the average distance
      from the liver to the stomach wall was 1.0 +/- 2.8 mm. The average dose for
      patients who received radioembolization to the left hepatic lobe was 109 +/- 57
      Gy. Fifty patients had tumor within 1 cm of the gastric wall. The average dose
      for patients who received radioembolization to the left hepatic lobe with tumor
      within 1 cm of the gastric wall was 121 +/- 41 Gy. There were no reportable or
      recordable medical events. Of the patients, 34% reported abdominal pain that was
      grade 1-2; 65% of the patients reported no abdominal pain. None of the 97
      patients developed a clinically evident GI ulcer. CONCLUSION: Patients with left
      lobe tumors adjacent to or abutting the stomach do not exhibit acute or chronic
      radiation effects following radioembolization with glass microspheres.

PMID- 26194716
TI  - Prognostic value of metabolic parameters and clinical impact of 18F-fluorocholine
      PET/CT in biochemical recurrent prostate cancer.
AB  - PURPOSE: To evaluate the therapeutic impact of (18)F-fluorocholine (FCH) PET/CT
      in biochemical recurrent prostate cancer (PC) and to investigate the value of
      quantitative FCH PET/CT parameters in predicting progression-free survival (PFS).
      METHODS: This retrospective study included 172 consecutive patients with PC who
      underwent FCH PET/CT for biochemical recurrence. Mean rising PSA was 10.7 +/-
      35.0 ng/ml. Patients with positive FCH PET were classified into three groups:
      those with uptake only in the prostatic bed, those with locoregional disease, and
      those with distant metastases. Referring physicians were asked to indicate the
      hypothetical therapeutic strategy with and without the FCH PET/CT results.
      Clinical variables and PET parameters including SUVmax, SUVpeak, SUVmean, total
      lesion choline kinase activity (TLCKA) and standardized added metabolic activity
      (SAM) were recorded and a multivariate analysis was performed to determine the
      factors independently predicting PFS. RESULTS: In 137 of the 172 patients, the
      FCH PET/CT scan was positive, and of these, 29.9 % (41/137) had prostatic
      recurrence, 42.3 % (58/137) had pelvic lymph node recurrence with or without
      prostatic recurrence, and 27.7 % (38/137) had distant metastases. The FCH PET/CT
      result led to a change in treatment plan in 43.6 % (75/172) of the 172 patients.
      Treatment was changed in 49.6 % (68/137) of those with a positive FCH PET/CT scan
      and in 20 % (7/35) of those with a negative FCH PET/CT scan. After a median
      follow-up of 29.3 months (95 % CI 18.9 - 45.9 months), according to multivariate
      analysis age <70 years, SAM >=23 and SUVmean >=3 were parameters independently
      predicting PFS. A nomogram constructed using the three parameters showed 49
      months of PFS in patients with the best scores (0 or 1) and only 11 months in
      patients with a poor score (score 3). CONCLUSION: This study indicates that a
      positive FCH PET result in PC patients with biochemical recurrence predicts a
      shorter PFS and confirms the major impact of the FCH PET result on the management
      of biochemical recurrent PC.

PMID- 26194717
TI  - Clinical value of FDG-PET/CT in suspected paraneoplastic syndromes: a
      retrospective analysis of 137 patients.
AB  - PURPOSE: Paraneoplastic syndromes (PNS) are relatively infrequent manifestations
      appearing before or after a cancer declares itself. Autoimmune mechanisms may be
      involved, but their cause and pathogenesis are often unknown. Due to disparity of
      symptoms, PNS remain a major diagnostic challenge. We examined the value of FDG
      PET/CT for ruling in or out malignancy in a heterogeneous group of patients with
      suspected PNS. METHODS: We retrospectively extracted data from all patients
      referred 2009-2013 with suspected PNS. Data included age, sex, follow-up period,
      scan report, further diagnostic procedures, and final clinical diagnosis.
      Conclusions of the scan reports were compared to the final follow-up outcome as
      determined during an average follow-up of 31 months (range 6-51.5) in patients
      who were not diagnosed with cancer in immediate continuation of a positive PET/CT
      scan. RESULTS: A total of 137 patients were included. Main causes for referral
      were neurological (n = 67), rheumatological (n = 25), dermatological (n = 18),
      nephrological (n = 6), haematological (n = 2), abnormal biochemistry (n = 11),
      and others (n = 8). The cancer prevalence was 8.8%. The FDG-PET/CT results were
      as follows: nine true positives, 22 false positives, 103 true negatives, and
      three false negatives. Corresponding diagnostic values were: sensitivity 75%,
      specificity 82%, accuracy 82%, and positive and negative predictive values of 29%
      and 97%, respectively. CONCLUSION: FDG-PET/CT has in patients with suspected PNS
      an impressively high negative predictive value and may be of value in ruling out
      PNS, the more so, the more the number of false positives can be minimized or used
      in differential diagnosis. We believe that FDG-PET/CT may become an important
      adjunct to the work-up and triage of patients with suspected PNS.

PMID- 26194718
TI  - Chronotropic response to vasodilator-stress in patients submitted to myocardial
      perfusion imaging: impact on the accuracy in detecting coronary stenosis.
AB  - AIMS: A lower heart rate response (HRR) during vasodilator MPI has been shown to
      have a relevant adverse prognostic impact. We sought to evaluate the interaction
      among individual HRR to vasodilator stress and myocardial perfusion imaging (MPI)
      accuracy in patients with suspected ischemic heart disease (IHD). METHODS AND
      RESULTS: One hundred and sixty-five consecutive patients were submitted to
      vasodilator-stress MPI on a cardiac camera equipped with cadmium-zinc-thelluride
      detectors and coronary angiography. A coronary stenosis >70 % was considered
      significant. In every patient, the summed difference score (SDS) was computed
      from MPI images. Patients were categorized according to the tertiles of the
      distribution of individual HRR during dipyridamole: "Group 1" (HRR < 8 bpm;
      lowest tertile); "Group 2" (8 <= HRR <= 12 bpm; middle tertile); "Group 3" (HRR
      >12 bpm; highest tertile). Significant coronary artery disease (CAD) was present
      in 102 (62 %) patients. In the overall population, MPI showed a significant
      accuracy (AUC: 0.81, 95 % CI 0.74-0.86; p < 0.001) in unmasking the presence of
      significant coronary stenosis. Interestingly, in patients with a blunted HRR
      during dipyridamole ("Group 1") MPI showed a significantly lower sensitivity (68
      %) in detecting CAD than in those with a higher HRR ("Group 3") (91 %, p =
      0.007), despite a preserved specificity (76 % vs 77 %, P=NS). Similarly, the
      correlation among CAD extent and post-stress LV functional stunning was limited
      to "Group 3" patients, while it disappeared in those with blunted HRR.
      CONCLUSIONS: In patients with suspected IHD, MPI sensitivity is strongly
      influenced by the magnitude of patient heart rate increase to the pharmacologic
      stressor, suggesting an interaction among blunted HRR and lower accuracy in
      unmasking CAD.

PMID- 26194719
TI  - Fluorescent radiocolloids: are hybrid tracers the future for lymphatic mapping?

PMID- 26194720
TI  - Risk factors, psychological impacts and current treatments of acne in  Shanghai
      area of China.
AB  - Acne is one complex skin disorders, which can lead to adverse psychological
      effects. Multiple factors are correlated with risk of acne and several treatments
      have been explored. The prevalence and risk factors are suspected to be varied in
      different populations with different genetic backgrounds and lifestyle.
      Therefore, this study investigated the risk factors, psychological impacts and
      current treatments of acne in Shanghai area of China by a retrospective
      questionnaire study. This study showed that the subjects with family history
      (especially paternal history) were prone to develop severe acne (p<0.001).
      Besides, patients with severe acne might exhibit more severe psychological
      disorders (p<0.001). The most frequently used methods were pharmacological
      treatments. These results indicate that acne is prone to induce severe
      psychological disorders, and could be affected by multiple factors. Furthermore,
      these results provide valuable reference for exploring the preventive measures
      and treatments of acne in Shanghai area of China.

PMID- 26194721
TI  - Meta-analysis of randomized controlled trials of renal denervation in treatment
      resistant hypertension.
AB  - OBJECTIVE: The blood pressure (BP)-lowering effect of renal sympathetic nervous
      denervation (RDN) in resistant hypertension (rHT) shows large variation among
      studies. METHODS: We meta-analyzed summary statistics of randomized clinical
      trials on RDN in rHT. For continuous outcomes, we assessed heterogeneity by
      Cochran's Q test and used random-effect models weighted for the inverse of the
      variance. We assessed safety by assessing the risk of major adverse events from
      stratified contingency tables. RESULTS: Of 5652 patients screened in seven
      trials, 985 (17.4%) qualified and were randomized to control (n = 397) or RDN
      with SYMPLICITY(TM) catheters (n = 588). Follow-up was 6 months. In both control
      and RDN patients, antihypertensive treatment was continued or optimized. At
      enrolment, age averaged 58.1 years, systolic/diastolic office and 24 h BP
      168.5/93.3 mmHg and 151.8/86.1 mmHg, respectively, and estimated glomerular
      filtration rate (eGFR) 79.3 ml/min/1.73 m2. For BP outcomes, there was
      heterogeneity among trials. Pooled effects (control minus RDN) were -4.9/-3.5
      mmHg (95% confidence interval, -20.9 to 11.1/-8.9 to 1.9) for office BP, -2.8/
      1.5 mmHg (-6.5 to 0.8/-3.3 to 0.4) for 24 h BP and 0.81 ml/min/1.73 m2 (-1.69 to
      3.30) for eGFR. Removing one trial at a time produced confirmatory results.
      Adverse events occurred in 7.4% and 9.9% of control and RDN patients,
      respectively (p = 0.24). CONCLUSION: In selected rHT patients maintained on
      antihypertensive drugs, RDN with the SYMPLICITY systems does not significantly
      decrease BP but is safe. Future trials with next-generation catheters should aim
      at identifying responders in patients with evidence of sympathetic nervous
      overactivity.

PMID- 26194722
TI  - Phylogenic diversity and tissue specificity of fungal endophytes associated with
      the pharmaceutical plant, Stellera chamaejasme L. revealed by a cultivation
      independent approach.
AB  - The fungal endophytes associated with medicinal plants have been demonstrated as
      a reservoir with novel natural products useful in medicine and agriculture. It is
      desirable to explore the species composition, diversity and tissue specificity of
      endophytic fungi that inhabit in different tissues of medicinal plants. In this
      study, a culture-independent survey of fungal diversity in the rhizosphere,
      leaves, stems and roots of a toxic medicinal plant, Stellera chamaejasme L., was
      conducted by sequence analysis of clone libraries of the partial internal
      transcribed spacer region. Altogether, 145 fungal OTUs (operational taxonomic
      units), represented by 464 sequences, were found in four samples, of these 109
      OTUs (75.2 %) belonging to Ascomycota, 20 (13.8 %) to Basidiomycota, 14 (9.7 %)
      to Zygomycota, 1 (0.7 %) to Chytridiomycota, and 1 (0.7 %) to Glomeromycota. The
      richness and diversity of fungal communities were strongly influenced by plant
      tissue environments, and the roots are associated with a surprisingly rich
      endophyte community. The endophyte assemblages associated with S. chamaejasme
      were strongly shaped by plant tissue environments, and exhibited a certain degree
      of tissue specificity. Our results suggested that a wide variety of fungal
      assemblages inhabit in S. chamaejasme, and plant tissue environments
      conspicuously influence endophyte community structure.

PMID- 26194723
TI  - Neutrophils fan cancer's flames.

PMID- 26194725
TI  - What is the future of biomedical research?
AB  - Randomized controlled trials require hard work and financial commitment, whereas
      meta-analyses and systematic reviews can be relatively easy to perform and often
      get published in high impact journals. Many researchers might decide to devote
      themselves to the latter approach, resulting in a negative impact on clinical
      research. We have reviewed the number of indexed meta-analyses and systematic
      reviews on PubMed and compared it with the number of randomized controlled trials
      over the same period. Statistical analysis showed an exponential increase of
      synthetic studies with respect to randomized trials. The ratio between RCTs and
      synthetic studies is quickly decreasing. These results suggest that a growing
      number of researchers might prefer to commit themselves to synthetic studies more
      than be involved in more time consuming and funds demanding observational trials.
      If we are unable to invert this trend, in the future we will have a growing
      number of synthetic studies utilizing someone else's original data and fewer raw
      data to base our knowledge upon. 

PMID- 26194724
TI  - Chimeric adaptor proteins translocate diverse type VI secretion system effectors
      in Vibrio cholerae.
AB  - Vibrio cholerae is a diverse species of Gram-negative bacteria, commonly found in
      the aquatic environment and the causative agent of the potentially deadly disease
      cholera. These bacteria employ a type VI secretion system (T6SS) when they
      encounter prokaryotic and eukaryotic competitors. This contractile puncturing
      device translocates a set of effector proteins into neighboring cells.
      Translocated effectors are toxic unless the targeted cell produces immunity
      proteins that bind and deactivate incoming effectors. Comparison of multiple V.
      cholerae strains indicates that effectors are encoded in T6SS effector modules on
      mobile genetic elements. We identified a diverse group of chimeric T6SS adaptor
      proteins required for the translocation of diverse effectors encoded in modules.
      An example for a T6SS effector that requires T6SS adaptor protein 1 (Tap-1) is
      TseL found in pandemic V. cholerae O1 serogroup strains and other clinical
      isolates. We propose a model in which Tap-1 is required for loading TseL onto the
      secretion apparatus. After T6SS-mediated TseL export is completed, Tap-1 is
      retained in the bacterial cell to load other T6SS machines. 

PMID- 26194726
TI  - Unpacking Sleep and Suicide in Older Adults in a Combined Online Sample.
AB  - OBJECTIVE: Duration of insomnia symptoms and nightmares are related to suicidal
      risk in young adults independent of current symptoms of insomnia, nightmares,
      anxiety, depression, and PTSD. However, this relation has yet to be examined
      among older adults, despite older adults being at higher risk of suicidal
      behavior. Further, the current study aims to replicate previous research among
      younger adults showing that insomnia symptoms and nightmares are associated with
      suicide risk independent of the interpersonal psychological theory of suicide
      (IPTS). METHODS: The present study utilized 167 participants age 55 and older
      obtained by combining two independent mTurk data collections of adults in the
      United States. RESULTS: In the current sample, duration of nightmares was
      associated with suicide risk in older adults independent of symptoms of current
      insomnia and nightmares, duration of insomnia, and symptoms of PTSD, anhedonia,
      and the IPTS. CONCLUSIONS: Our findings suggest that the duration of nightmares
      (i.e., how long someone has been experiencing nightmares) predict substantial
      variance in suicide risk among older adults in addition to the risk factors
      typically examined. Thus, assessment of sleep dysfunction is important when
      assessing suicide risk among older adults.

PMID- 26194727
TI  - Measuring Sleep Efficiency: What Should the Denominator Be?
AB  - ABSTRACT: Inconsistency in operationally defining sleep efficiency (SE) creates
      confusion with regard to the conceptualization and use of the construct by
      researchers and clinicians. The source of the inconsistency is the denominator of
      the widely published operational definition of SE: ratio of total sleep time
      (TST) to time in bed (TIB) (multiplied by 100 to yield a percentage). When taken
      literally, TIB includes non-sleep-related activity (e.g., reading, texting,
      conversing with a partner, watching television) both prior to initiating sleep
      and after the final awakening. However, the construct of SE refers to TST
      compared to the amount of time spent attempting to initially fall asleep and
      sleep discontinuity. Non-sleep related activities in bed do not reflect that
      construct. Also, time out of bed during nighttime awakenings, a manifestation of
      sleep discontinuity, should be included in the SE denominator. Using TIB as the
      denominator can also create a methodological problem when SE is an outcome
      measure in sleep intervention research. It is proposed that research and practice
      would benefit by clarifying and adopting a consistent operational definition that
      more accurately captures the construct of SE. An alternate denominator, duration
      of the sleep episode (DSE), is suggested, where DSE = sleep onset latency (SOL) +
      TST + time awake after initial sleep onset but before the final awakening (WASO)
      + time attempting to sleep after final awakening (TASAFA). The proposed formula
      for SE would be: SE = TST / DSE (* 100). DSE can be easily calculated using
      standard sleep diary entries along with one item from the Expanded Consensus
      Sleep Diary. Implications for insomnia research and practice are discussed.

PMID- 26194728
TI  - Effects of Suvorexant, an Orexin Receptor Antagonist, on Respiration during Sleep
      In Patients with Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: To investigate the respiratory effects of suvorexant, an orexin
      receptor antagonist for treating insomnia, in patients with obstructive sleep
      apnea (OSA). METHODS: This was a randomized, double-blind, placebo-controlled, 2
      period (4 days per period), crossover, sleep laboratory study. Twenty-six
      patients aged 18-65 years with mild (apnea-hypopnea index [AHI] >= 5 and < 15) to
      moderate (AHI >= 15 and < 30) OSA were randomized to receive suvorexant 40 mg or
      placebo in period-1 and then crossed over to the other treatment in period-2.
      Breathing during sleep was measured by AHI (primary endpoint) and oxygen
      saturation assessed by pulse oximetry (SpO2, secondary endpoint). The study was
      powered to rule out a mean increase in AHI between suvorexant and placebo of 5 or
      greater on Day 4. RESULTS: There was a small increase in mean AHI (2.66) in OSA
      patients after multiple doses of suvorexant relative to placebo, with the upper
      90% CI bound slightly exceeding 5.00 (0.22, 5.09). No increase in mean AHI was
      observed after a single dose of suvorexant versus placebo (mean difference = 
      0.47 [-3.20, 2.26]), and there was no treatment effect on mean SpO2 during total
      sleep time after single or multiple doses (Day 1: mean difference = -0.04 [-0.49,
      0.42]; Day 4: mean difference = -0.06 [-0.45, 0.33]). There was inter- and intra
      individual variability in suvorexant respiratory effects. CONCLUSIONS: Suvorexant
      40 mg, twice the 20 mg maximum recommended dose for treating insomnia in the USA
      and Japan, does not appear to have clinically important respiratory effects
      during sleep in patients with mild to moderate OSA as assessed by mean AHI and
      SpO2. Due to inter- and intra-individual variability in respiratory effects,
      suvorexant should be used with caution in patients with compromised respiratory
      function, and at the lowest effective dose. CLINICAL TRIAL REGISTRATION:
      clinicaltrials.gov, NCT01300455.

PMID- 26194729
TI  - Nocturnal Hypoxemia Is Associated with White Matter Hyperintensities in Patients
      with a Minor Stroke or Transient Ischemic Attack.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a risk factor for stroke,
      which is modulated by accompanying nocturnal hypoxemia. White matter
      hyperintensities (WMH) share many of the same risk factors as stroke. The purpose
      of this study was to investigate whether OSA and nocturnal hypoxemia are
      associated with white matter disease in patients with minor stroke and transient
      ischemic attack. METHODS: Patients with minor stroke or TIA were recruited. Level
      3 diagnostic sleep testing was used to diagnose OSA and quantify nocturnal
      hypoxemia. Significant OSA was defined as respiratory disturbance index >= 15,
      and nocturnal hypoxemia was defined as oxyhemoglobin saturation < 90% for >= 12%
      of total monitoring time. WMH were assessed and quantified on FLAIR MRI. The
      volume of WMH was compared between those with and without significant OSA and
      between those with and without nocturnal hypoxemia. RESULTS: One hundred nine
      patients were included. Thirty-four (31%) had OSA and 37 (34%) had nocturnal
      hypoxemia. Total WMH volume was significantly greater in the OSA than in the non
      OSA groups (p = 0.04). WMH volume was also significantly higher in the hypoxic
      than the non-hypoxic groups (p = 0.001). Mutivariable analysis with adjustment
      for age, hypertension, and diabetes showed that nocturnal hypoxemia was
      independently associated with WMH volume (p = 0.03) but OSA was not (p = 0.29).
      CONCLUSIONS: We conclude that nocturnal hypoxemia, predominantly related to OSA,
      is independently associated with WMH in patients who present with minor ischemic
      stroke and TIA and may contribute to its pathogenesis.

PMID- 26194731
TI  - How the CPAP Download Unexpectedly Helped a Young Man with a Sleeping Problem.

PMID- 26194730
TI  - Temporal Characteristics of the Sleep EEG Power Spectrum in Critically Ill
      Children.
AB  - STUDY OBJECTIVES: Although empirical evidence is limited, critical illness in
      children is associated with disruption of the normal sleep-wake rhythm. The
      objective of the current study was to examine the temporal characteristics of the
      sleep electroencephalogram (EEG) in a sample of children with critical illness.
      METHODS: Limited montage EEG recordings were collected for at least 24 hours from
      8 critically ill children on mechanical ventilation for respiratory failure in a
      pediatric intensive care unit (PICU) of a tertiary-care hospital. Each PICU
      patient was age- and gender-matched to a healthy subject from the community.
      Power spectral analysis with the fast Fourier transform (FFT) was used to
      characterize EEG spectral power and categorized into 4 frequency bands: delta
      (0.8 to 4.0 Hz), theta (4.1 to 8.0 Hz), alpha (8.1 to 13.0 Hz), and beta1/beta2
      (13.1 to 20.0 Hz). RESULTS: PICU patients did not manifest the ultradian
      variability in EEG power spectra including the typical increase in delta-power
      during the first third of the night that was observed in healthy children.
      Differences noted included significantly lower mean nighttime delta and theta
      power in the PICU patients compared to healthy children (p < 0.001). Moreover, in
      the PICU patients, mean delta and theta power were higher during daytime hours
      than nighttime hours (p < 0.001). CONCLUSIONS: The results presented herein
      challenge the assumption that children experience restorative sleep during
      critical illness, highlighting the need for interventional studies to determine
      whether sleep promotion improves outcomes in critically ill children undergoing
      active neurocognitive development.

PMID- 26194733
TI  - Evolve Sleep: Optimized Solutions To Help Your Sleep Medicine Practice Thrive.

PMID- 26194734
TI  - Relationship between Clinical and Polysomnography Measures Corrected for CPAP
      Use.
AB  - OBJECTIVES: The changes in patient-reported measures of obstructive sleep apnea
      (OSA) burden are largely discordant with the change in apnea-hypopnea index (AHI)
      and other polysomnography measures before and after treatment. For patients
      treated with continuous positive airway pressure (CPAP), some investigators have
      theorized that this discordance is due in part to the variability in CPAP use. We
      aim to test the hypothesis that patient-reported outcomes of CPAP treatment have
      stronger correlations with AHI when it is corrected for mean nightly CPAP use.
      METHODS: This was a cross-sectional study of 459 adults treated with CPAP for
      OSA. Five patient-reported measures of OSA burden were collected at baseline and
      after 6 months of CPAP therapy. The correlations between the change in each
      patient-reported measure and the change in AHI as well as mean nightly AHI
      (corrected for CPAP use with a weighted average formula) were measured after 6
      months of treatment. The same analysis was repeated for 4 additional
      polysomnography measures, including apnea index, arousal index, lowest
      oxyhemoglobin saturation, and desaturation index. RESULTS: The change in AHI was
      weakly but significantly correlated with change in 2 of the 5 clinical measures.
      The change in mean nightly AHI demonstrated statistically significant
      correlations with 4 out of 5 clinical measures, though each with coefficients
      less than 0.3. Similar results were seen for apnea index, arousal index, lowest
      oxyhemoglobin saturation, and desaturation index. CONCLUSIONS: Correction for
      CPAP use yielded overall small but significant improvements in the correlations
      between patient-reported measures of sleep apnea burden and polysomnography
      measures after 6 months of treatment.

PMID- 26194736
TI  - Escherichia coli of sequence type 3835 carrying bla NDM-1, bla CTX-M-15, bla CMY
      42 and bla SHV-12.
AB  - New Delhi metallo-beta-lactamase (NDM) represents a serious challenge for
      treatment and public health. A carbapenem-resistant Escherichia coli clinical
      strain WCHEC13-8 was subjected to antimicrobial susceptibility tests, whole
      genome sequencing and conjugation experiments. It was resistant to imipenem (MIC,
      >256 MUg/ml) and meropenem (MIC, 128 MUg/ml) and belonged to ST3835. bla NDM-1
      was the only carbapenemase gene detected. Strain WCHEC13-8 also had a plasmid
      borne AmpC gene (bla CMY-42) and two extended-spectrum beta-lactamase genes (bla
      CTX-M-15 and bla SHV-12). bla NDM-1 and bla SHV-12 were carried by a 54-kb IncX3
      self-transmissible plasmid, which is identical to plasmid pNDM-HF727 from
      Enterobacter cloacae. bla CMY-42 was carried by a 64-kb IncI1 plasmid and bla CTX
      M-15 was located on a 141-kb plasmid with multiple F replicons (replicon type:
      F36:A4:B1). bla CMY-42 was in a complicated context and the mobilisation of bla
      CMY-42 was due to the transposition of ISEcp1 by misidentifying its right-end
      boundary. Genetic context of bla NDM-1 in strain WCHEC13-8 was closely related to
      those on IncX3 plasmids in various Enterobacteriaceae species in China. In
      conclusion, a multidrug-resistant ST3835 E. coli clinical strain carrying bla NDM
      1, bla CTX-M-15, bla CMY-42 and bla SHV-12 was identified. IncX3 plasmids may be
      making a significant contribution to the dissemination of bla NDM among
      Enterobacteriaceae in China.

PMID- 26194735
TI  - Polysomnographic Study of Sleep in Survivors of Breast Cancer.
AB  - STUDY OBJECTIVE: Insomnia is a frequent complaint in breast cancer patients
      during and after treatment. Breast cancer survivors, 1-10 years posttreatment,
      underwent in-lab polysomnography (PSG) to objectively define the insomnia in
      those patients with such a complaint. METHODS: Twenty-six breast cancer survivors
      (aged 39-80, mean 54.0 months posttreatment) spent 2 nights in the sleep
      laboratory. Sleep on Night 2 was scored for sleep stages, sleep onset latency,
      REM sleep onset latency, wake time, apneas and hypopneas, periodic limb movements
      and arousals. Subjects were allocated into 2 groups by their scores on the
      Pittsburgh Sleep Quality Index (PSQI): no/ mild sleep disturbance (PSQI score <=
      9, n = 15) or moderate/ severe sleep disturbance (PSQI >= 10, n = 11). RESULTS:
      Standard PSG/EEG parameters failed to differentiate insomniacs from non
      insomniacs. The single variable that distinguished the insomnia group was
      periodic limb movements in sleep (PLMS). PLMS were significantly correlated (r ?
      0.7, p < 0.02) with subjective report of insomnia on PSQI and insomnia severity
      index. Log[Number of PLMS] was higher in the moderate/severe insomnia group (p =
      0.008). Five of 11 patients in the moderate/severe insomnia group had a PLMS
      index >= 15, compared to only one of 15 patients in the none/mild insomnia group
      (p = 0.02). Menopausal symptoms and use of caffeine, hypnotics, and
      antidepressants were unrelated to insomnia severity or PLMS. CONCLUSIONS: PLMS
      was the sole PSG variable that separated breast cancer survivors with
      moderate/severe insomnia from those with no/mild sleep disturbance. Further study
      of the incidence and significance of PLMS in breast cancer survivors with the
      complaint of insomnia is merited.

PMID- 26194737
TI  - Improving the Informed Consent Conversation: A Standardized Checklist that Is
      Patient Centered, Quality Driven, and Legally Sound.
AB  - The informed consent conversation is a key component of patient-centered
      medicine, a concept that emphasizes the importance of patients actively
      participating in their care. Studies reveal that many informed consent
      conversations throughout medical practice lack essential elements and leave
      patients' needs unmet. This review addresses these deficiencies, discusses
      solutions, and introduces a standardized checklist that values the patient's role
      in shared decision making during the informed consent conversation. The checklist
      could be particularly helpful to interventional radiologists and other consulting
      physicians who usually obtain informed consent early in their encounters with
      patients. 

PMID- 26194738
TI  - A Comparison of DSM-5 and DSM-IV Diagnostic Criteria for Posttraumatic Stress
      Disorder in Traumatized Refugees.
AB  - The aim of this study was to compare the prevalence rate and factor structure of
      posttraumatic stress disorder (PTSD) based on the diagnostic criteria of the
      fourth and fifth editions of the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-IV; DSM-5; American Psychiatric Association, , ) in traumatized
      refugees. There were 134 adult treatment-seeking, severely and multiply
      traumatized patients from various refugee backgrounds were assessed in their
      mother tongue using a computerized set of questionnaires consisting of a trauma
      list, the Posttraumatic Diagnostic Scale, and the new PTSD items that had been
      suggested by the DSM-5 Task Force of the American Psychiatric Association. Using
      DSM-IV, 60.4% of participants met diagnostic criteria for PTSD; using DSM-5, only
      49.3% fulfilled all criteria (p < .001). Confirmatory factor analysis of DSM-IV
      and DSM-5 items showed good and comparable model fits. Furthermore,
      classification functions in the DSM-5 were satisfactory. The new Cluster D
      symptoms showed relatively high sensitivity, specificity, positive predictive
      power, and negative predictive power. The DSM-5 symptom structure appears to be
      applicable to traumatized refugees. Negative alterations in cognitions and mood
      may be especially useful for clinicians, not only to determine the extent to
      which an individual refugee is likely to meet criteria for PTSD, but also in
      providing targets for clinical intervention.

PMID- 26194739
TI  - F-18 DG PET/CT ear chondritis image in a patient with giant cell arteritis.

PMID- 26194740
TI  - Cervical rib mimicking supraclavicular mass.

PMID- 26194741
TI  - A prospective evaluation of dental and periodontal status in patients with
      suspected Sjogren's syndrome.

PMID- 26194742
TI  - Floral nectar production and nectary structure of a bee-pollinated shrub from
      Neotropical savanna.
AB  - Biotic pollination is critical for tropical ecosystem functioning, and nectar
      plays an essential role as it represents the main trophic resource for
      pollinators. Nevertheless, little is known about the mechanisms that underlie its
      production, which is essential for understanding the basis of nectar-mediated
      interactions in ecological and evolutionary approaches. Therefore, this study
      explores the relationship between the nectar secretion pattern and nectary
      functional changes in Anemopaegma album, a bee-pollinated species. We analysed
      the pattern of nectar production under field conditions and investigated floral
      nectary structural changes in two different developmental stages using light,
      transmission and scanning electron microscopy. We measured 30.95 +/- 23.02 MUl
      (mean +/- SD, n = 30) of nectar accumulated inside the nectar chamber (29.26 +/-
      3.48% sucrose equivalents) at the moment of flower opening. Nectar removal did
      not influence the pattern of floral nectar production in terms of volume or total
      sugar but reduced the concentration of the nectar produced during the first 24 h
      of anthesis. The nectary consisted of an epidermis, a nectary parenchyma and a
      subnectary parenchyma supplied only by phloem. Starch grains decreased in size
      and abundance from the subnectary parenchyma toward the epidermis. We observed
      the degradation of starch grains and incorporation of amyloplasts into vacuoles
      at the pre-anthesis stage as well as the transformation of amyloplasts into
      elaioplasts during anthesis. Nectar secretion was continuous during the A. album
      flower life span, which was related to the functional features of its floral
      nectary, especially the presence of starch stored in the parenchyma.

PMID- 26194743
TI  - Perspectives and reflections on the practice of behaviour change communication
      for infant and young child feeding.
AB  - Behaviour change communication (BCC) is a critical component of infant and young
      child feeding (IYCF) interventions. In this study we asked BCC practitioners
      working in low- and middle-income countries to participate in an examination of
      BCC practice. We focus here on results of their personal reflections related to
      larger issues of practice. We used a combination of iterative triangulation and
      snowball sampling procedures to obtain a sample of 29 BCC professionals. Major
      themes include (1) participants using tools and guidelines to structure their
      work, and many consider their organisation's tools to be their most important
      contribution to the field; (2) they value research to facilitate programme design
      and implementation; (3) half felt research needed to increase; (4) they have a
      strong commitment to respecting cultural beliefs and culturally appropriate
      programming; (5) they are concerned about lack of a strong theoretical foundation
      for their work. Based on participants' perspectives and the authors' reflections,
      we identified the following needs: (1) conducting a systematic examination of the
      alternative theoretical structures that are available for nutrition BCC, followed
      by a review of the evidence base and suggestions for future programmatic research
      to fill the gaps in knowledge; (2) developing a checklist of common patterns to
      facilitate efficiency in formative research; (3) developing an analytic
      compendium of current IYCF BCC guidelines and tools; (4) developing tools and
      guidelines that cover the full programme process, including use of innovative
      channels to support 'scaling up nutrition'; and (5) continued support for
      programmes of proven effectiveness. 

PMID- 26194744
TI  - Obesity adversely affects serum anti-mullerian hormone (AMH) levels in Caucasian
      women.
AB  - OBJECTIVE: Previous studies regarding the effect of obesity on serum anti
      mullerian hormone (AMH) levels have been conflicting. Our aim was to determine
      the effect of obesity on serum AMH levels among women from different racial
      backgrounds. METHODS: The medical records of 350 women (159 Caucasian, 99 African
      American, 58 Hispanic, 34 Asian with ages 16-46) evaluated for infertility at an
      academic-affiliated center and who had AMH levels measured as part of their
      evaluation were reviewed. Age, AMH, body mass index (BMI), self-reported race,
      etiology of infertility, smoking history, maximum serum early follicular follicle
      stimulating hormone (FSH) levels, antral follicle count (AFC), and history of
      ovarian surgery, chemotherapy, or radiotherapy were recorded. RESULTS: Age
      correlated negatively with AMH and antral follicle count across all races (p <
      0.05). After adjusting for age, polycystic ovary syndrome diagnosis, and smoking,
      elevated BMI had a negative correlation with AMH in Caucasian women (beta = 0.17,
      p = 0.01) but not in African-American, Hispanic, or Asian women. CONCLUSION:
      Elevated BMI correlates negatively with AMH in Caucasian women but not in African
      American, Hispanic, or Asian women. Additional studies are needed to elucidate
      further the effect of race on the interaction between obesity and ovarian
      reserve.

PMID- 26194745
TI  - Diagnosis of a large splenic tumor in a dog: computed tomography versus magnetic
      resonance imaging.
AB  - This study demonstrated magnetic resonance imaging (MRI) and computed tomography
      for large-sized splenic hemangiosarcoma. Radiography and ultrasonography revealed
      the presence of a large-sized soft-tissue mass in the cranial abdomen. Computed
      tomography showed hypoattenuating mass. The mass was located in contact with
      liver, spleen and stomach, and the origin of the mass remained ambiguous. The
      mass was T2-hyperintense and T1-hypointense with mild contrast enhancement. MRI
      allowed a differentiation between large-sized tumor and neighboring normal
      structure, and the mass was consequently identified as arising from spleen. These
      results suggested that MRI might be a useful tool to visualize large-sized
      splenic tumors and improve the accuracy of diagnosis. 

PMID- 26194746
TI  - Outcomes including liver histology after liver transplantation for chronic
      hepatitis B using oral antiviral therapy alone.
AB  - The outcomes of hepatitis B virus (HBV)-related hepatitis after liver
      transplantation (LT) without hepatitis B immune globulin (HBIG) is not well
      documented. This study aims to determine the outcomes of chronic hepatitis B
      (CHB) patients using an HBIG-free regimen. All biopsies performed 3 months or
      more after LT in consecutive CHB patients transplanted from 2003 to 2012 were
      reviewed. None of the patients received HBIG. Results of all liver histologies
      were reviewed to determine the cause of graft dysfunction. Of the 435 patients
      transplanted during this period, 263 liver biopsies were performed in 144
      patients. Thirty-six patients were positive for hepatitis B surface antigen
      (HBsAg) with undetectable HBV DNA at the time of biopsy, and none had
      histological evidence of HBV infection. Of the 263 biopsies, 44 (17%) had
      evidence of fibrosis. There was a significantly higher rate of fibrosis in those
      with large duct obstruction compared to those without (51% versus 9%,
      respectively; P < 0.001). Of the 291 patients without a liver biopsy during the
      same period, 43 were HBsAg+. Seven patients had evidence of virological rebound,
      of whom 6 had evidence of rtM204V/I mutation and 1 had recurrence of
      hepatocellular carcinoma with low-level rebound and wild-type virus. In
      conclusion, for patients without virological rebound, positive serum HBsAg was
      not associated with histological evidence of HBV-related hepatitis after LT. To
      prevent virological rebound, nucleos(t)ide analogues with higher barriers to
      resistance should be used.

PMID- 26194748
TI  - [Analysis of the joint and a posteriori probability between primary empty sella,
      its comorbidities and audiovestibular pathology].
AB  - BACKGROUND: Primary empty sella is a herniation of the sellar diaphragm into the
      pituitary space. It is an incidental finding and patients may manifest
      neurological, ophthalmological and/or endocrine disorders. Episodes of vertigo,
      dizziness, and hearing loss, have been reported. OBJECTIVE: To determine the
      conditional probability, as well as the statistical dependency, through the
      Bayesian analysis in patients with primary empty sella and audiovestibular
      disorders. PATIENTS: Individuals who attended the National Rehabilitation
      Institute from January 2010 to December 2011, diagnosed with primary empty sella
      and audiovestibular disorders. MATERIAL AND METHODS: An analysis was performed on
      a sample of 18 patients with a diagnosis of primary empty sella confirmed with
      magnetic resonance studies and who had signs of vertigo, hearing loss and
      dizziness. RESULTS: Of the 18 patients studied, 3 (16.66%) had primary empty
      sella as the only clinical evidence. In 9 patients (50%) empty sella was
      associated with vertigo, and 16 patients (88.88%) were diagnosed with hearing
      loss, with sensorineural hearing loss being the most frequent (77.77%). The
      intersection between the proportions of primary empty sella with the presence and
      type of hearing loss was calculated. Thus for sensorineural hearing loss, the
      calculated ratio was P(AB)=0.6912, and for conductive and mixed hearing loss the
      value of P(AB)=0.0493 in both cases. CONCLUSIONS: Bayesian analysis and
      conditional probability enables the dependence between two or more variables to
      be calculated. In this study both mathematical models were used to analyse
      comorbidities and audiovestibular disorders in patients diagnosed with primary
      empty sella.

PMID- 26194750
TI  - The mouse antibody heavy chain repertoire is germline-focused and highly variable
      between inbred strains.
AB  - The human and mouse antibody repertoires are formed by identical processes, but
      like all small animals, mice only have sufficient lymphocytes to express a small
      part of the potential antibody repertoire. In this study, we determined how the
      heavy chain repertoires of two mouse strains are generated. Analysis of IgM- and
      IgG-associated VDJ rearrangements generated by high-throughput sequencing
      confirmed the presence of 99 functional immunoglobulin heavy chain variable
      (IGHV) genes in the C57BL/6 genome, and inferred the presence of 164 IGHV genes
      in the BALB/c genome. Remarkably, only five IGHV sequences were common to both
      strains. Compared with humans, little N nucleotide addition was seen in the
      junctions of mouse VDJ genes. Germline human IgG-associated IGHV genes are rare,
      but many murine IgG-associated IGHV genes were unmutated. Together these results
      suggest that the expressed mouse repertoire is more germline-focused than the
      human repertoire. The apparently divergent germline repertoires of the mouse
      strains are discussed with reference to reports that inbred mouse strains carry
      blocks of genes derived from each of the three subspecies of the house mouse. We
      hypothesize that the germline genes of BALB/c and C57BL/6 mice may originally
      have evolved to generate distinct germline-focused antibody repertoires in the
      different mouse subspecies. 

PMID- 26194749
TI  - The evolution within us.
AB  - The B-cell immune response is a remarkable evolutionary system found in jawed
      vertebrates. B-cell receptors, the membrane-bound form of antibodies, are capable
      of evolving high affinity to almost any foreign protein. High germline diversity
      and rapid evolution upon encounter with antigen explain the general adaptability
      of B-cell populations, but the dynamics of repertoires are less well understood.
      These dynamics are scientifically and clinically important. After highlighting
      the remarkable characteristics of naive and experienced B-cell repertoires,
      especially biased usage of genes encoding the B-cell receptors, we contrast
      methods of sequence analysis and their attempts to explain patterns of B-cell
      evolution. These phylogenetic approaches are currently unlinked to explicit
      models of B-cell competition, which analyse repertoire evolution at the level of
      phenotype, the affinities and specificities to particular antigenic sites. The
      models, in turn, suggest how chance, infection history and other factors
      contribute to different patterns of immunodominance and protection between
      people. Challenges in rational vaccine design, specifically vaccines to induce
      broadly neutralizing antibodies to HIV, underscore critical gaps in our
      understanding of B cells' evolutionary and ecological dynamics. 

PMID- 26194751
TI  - Ageing of the B-cell repertoire.
AB  - Older people are more susceptible to infection, less responsive to vaccination
      and have a more inflammatory immune environment. Using spectratype analysis, we
      have previously shown that the B-cell repertoire of older people shows evidence
      of inappropriate clonal expansions in the absence of challenge, and that this
      loss of B-cell diversity correlates with poor health. Studies on response to
      vaccination, using both spectratyping and high-throughput sequencing of the
      repertoire, indicate that older responses to challenge are lacking in magnitude
      and/or delayed significantly. Also that some of the biologically significant
      differences may be in different classes of antibody. We have also previously
      shown that normal young B-cell repertoires can vary between different phenotypic
      subsets of B cells. In this paper, we present an analysis of immunoglobulin
      repertoire in different subclasses of antibody in five different populations of B
      cell, and show how the repertoire in these different groups changes with age.
      Although some age-related repertoire differences occur in naive cells, before
      exogenous antigen exposure, we see indications that there is a general
      dysregulation of the selective forces that shape memory B-cell populations in
      older people. 

PMID- 26194752
TI  - Restricted, canonical, stereotyped and convergent immunoglobulin responses.
AB  - It is becoming evident that B-cell responses to particular epitopes or in
      particular contexts can be highly convergent at the molecular level. That is,
      depending on the epitope targeted, persons of diverse genetic backgrounds and
      immunological histories can use highly similar, stereotyped B-cell receptors
      (BCRs) for a particular response. In some cases, multiple people with immunity to
      a particular epitope or with a type of B-cell neoplasia will elicit antibodies
      encoded by essentially identical immunoglobulin gene rearrangements. In other
      cases, particular VH genes encode antibodies important for immunity against
      pathogens such as influenza and HIV. It appears that the conserved antibody
      structures driving these stereotyped responses are highly limited and selected.
      There are interesting and important convergences in the types of stereotyped BCRs
      induced in conditions of immunity and B-cell-related pathology such as cancer and
      autoimmunity. By characterizing and understanding stereotyped B-cell responses,
      novel approaches to B-cell immunity and in understanding the underlying causes of
      B-cell pathology may be discovered. In this paper, we will review stereotyped BCR
      responses in various contexts of B-cell immunity and pathology. 

PMID- 26194753
TI  - The analysis of clonal expansions in normal and autoimmune B cell repertoires.
AB  - Clones are the fundamental building blocks of immune repertoires. The number of
      different clones relates to the diversity of the repertoire, whereas their size
      and sequence diversity are linked to selective pressures. Selective pressures act
      both between clones and within different sequence variants of a clone.
      Understanding how clonal selection shapes the immune repertoire is one of the
      most basic questions in all of immunology. But how are individual clones defined?
      Here we discuss different approaches for defining clones, starting with how
      antibodies are diversified during different stages of B cell development. Next,
      we discuss how clones are defined using different experimental methods. We focus
      on high-throughput sequencing datasets, and the computational challenges and
      opportunities that these data have for mining the antibody repertoire landscape.
      We discuss methods that visualize sequence variants within the same clone and
      allow us to consider collections of shared mutations to determine which sequences
      share a common ancestry. Finally, we comment on features of frequently
      encountered expanded B cell clones that may be of particular interest in the
      setting of autoimmunity and other chronic conditions. 

PMID- 26194754
TI  - Assigning and visualizing germline genes in antibody repertoires.
AB  - Identifying the germline genes involved in immunoglobulin rearrangements is an
      essential first step in the analysis of antibody repertoires. Based on our prior
      work in analysing diverse recombinant viruses, we present IgSCUEAL
      (Immunoglobulin Subtype Classification Using Evolutionary ALgorithms), a
      phylogenetic approach to assign V and J regions of immunoglobulin sequences to
      their corresponding germline alleles, with D regions assigned using a simple
      pairwise alignment algorithm. We also develop an interactive web application for
      viewing the results, allowing the user to explore the frequency distribution of
      sequence assignments and CDR3 region length statistics, which is useful for
      summarizing repertoires, as well as a detailed viewer of rearrangements and
      region alignments for individual query sequences. We demonstrate the accuracy and
      utility of our method compared with sequence similarity-based approaches and
      other non-phylogenetic model-based approaches, using both simulated data and a
      set of evaluation datasets of human immunoglobulin heavy chain sequences.
      IgSCUEAL demonstrates the highest accuracy of V and J assignment amongst existing
      approaches, even when the reassorted sequence is highly mutated, and can
      successfully cluster sequences on the basis of shared V/J germline alleles. 

PMID- 26194756
TI  - The mutation patterns in B-cell immunoglobulin receptors reflect the influence of
      selection acting at multiple time-scales.
AB  - During the several-week course of an immune response, B cells undergo a process
      of clonal expansion, somatic hypermutation of the immunoglobulin (Ig) genes and
      affinity-dependent selection. Over a lifetime, each B cell may participate in
      multiple rounds of affinity maturation as part of different immune responses.
      These two time-scales for selection are apparent in the structure of B-cell
      lineage trees, which often contain a 'trunk' consisting of mutations that are
      shared across all members of a clone, and several branches that form a 'canopy'
      consisting of mutations that are shared by a subset of clone members. The
      influence of affinity maturation on the B-cell population can be inferred by
      analysing the pattern of somatic mutations in the Ig. While global analysis of
      mutation patterns has shown evidence of strong selection pressures shaping the B
      cell population, the effect of different time-scales of selection and
      diversification has not yet been studied. Analysis of B cells from blood samples
      of three healthy individuals identifies a range of clone sizes with lineage trees
      that can contain long trunks and canopies indicating the significant diversity
      introduced by the affinity maturation process. We here show that observed
      mutation patterns in the framework regions (FWRs) are determined by an almost
      purely purifying selection on both short and long time-scales. By contrast,
      complementarity determining regions (CDRs) are affected by a combination of
      purifying and antigen-driven positive selection on the short term, which leads to
      a net positive selection in the long term. In both the FWRs and CDRs, long-term
      selection is strongly dependent on the heavy chain variable gene family. 

PMID- 26194757
TI  - Inferring processes underlying B-cell repertoire diversity.
AB  - We quantify the VDJ recombination and somatic hypermutation processes in human B
      cells using probabilistic inference methods on high-throughput DNA sequence
      repertoires of human B-cell receptor heavy chains. Our analysis captures the
      statistical properties of the naive repertoire, first after its initial
      generation via VDJ recombination and then after selection for functionality. We
      also infer statistical properties of the somatic hypermutation machinery
      (exclusive of subsequent effects of selection). Our main results are the
      following: the B-cell repertoire is substantially more diverse than T-cell
      repertoires, owing to longer junctional insertions; sequences that pass initial
      selection are distinguished by having a higher probability of being generated in
      a VDJ recombination event; somatic hypermutations have a non-uniform distribution
      along the V gene that is well explained by an independent site model for the
      sequence context around the hypermutation site. 

PMID- 26194755
TI  - Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals.
AB  - Advances in immunoglobulin (Ig) sequencing technology are leading to new
      perspectives on immune system dynamics. Much research in this nascent field has
      focused on resolving immune responses to viral infection. However, the dynamics
      of B-cell diversity in early HIV infection, and in response to anti-retroviral
      therapy, are still poorly understood. Here, we investigate these dynamics through
      bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1
      infected patients, five of whom received anti-retroviral therapy during the first
      half of the study period. We applied previously published methods for visualizing
      and quantifying B-cell sequence diversity, including the Gini index, and compared
      their efficacy to alternative measures. While we found significantly greater
      clonal structure in HIV-infected patients versus healthy controls, within HIV
      patients, we observed no significant relationships between statistics of B-cell
      clonal expansion and clinical variables such as viral load and CD4(+) count.
      Although there are many potential explanations for this, we suggest that
      important factors include poor sampling resolution and complex B-cell dynamics
      that are difficult to summarize using simple summary statistics. Importantly, we
      find a significant association between observed Gini indices and sequencing read
      depth, and we conclude that more robust analytical methods and a closer
      integration of experimental and theoretical work is needed to further our
      understanding of B-cell repertoire diversity during viral infection. 

PMID- 26194758
TI  - Quantifying evolutionary constraints on B-cell affinity maturation.
AB  - The antibody repertoire of each individual is continuously updated by the
      evolutionary process of B-cell receptor (BCR) mutation and selection. It has
      recently become possible to gain detailed information concerning this process
      through high-throughput sequencing. Here, we develop modern statistical molecular
      evolution methods for the analysis of B-cell sequence data, and then apply them
      to a very deep short-read dataset of BCRs. We find that the substitution process
      is conserved across individuals but varies significantly across gene segments. We
      investigate selection on BCRs using a novel method that side-steps the
      difficulties encountered by previous work in differentiating between selection
      and motif-driven mutation; this is done through stochastic mapping and empirical
      Bayes estimators that compare the evolution of in-frame and out-of-frame
      rearrangements. We use this new method to derive a per-residue map of selection,
      which provides a more nuanced view of the constraints on framework and variable
      regions. 

PMID- 26194760
TI  - The challenges of modelling antibody repertoire dynamics in HIV infection.
AB  - Antibody affinity maturation by somatic hypermutation of B-cell immunoglobulin
      variable region genes has been studied for decades in various model systems using
      well-defined antigens. While much is known about the molecular details of the
      process, our understanding of the selective forces that generate affinity
      maturation are less well developed, particularly in the case of a co-evolving
      pathogen such as HIV. Despite this gap in understanding, high-throughput antibody
      sequence data are increasingly being collected to investigate the evolutionary
      trajectories of antibody lineages in HIV-infected individuals. Here, we review
      what is known in controlled experimental systems about the mechanisms underlying
      antibody selection and compare this to the observed temporal patterns of antibody
      evolution in HIV infection. We describe how our current understanding of antibody
      selection mechanisms leaves questions about antibody dynamics in HIV infection
      unanswered. Without a mechanistic understanding of antibody selection in the
      context of a co-evolving viral population, modelling and analysis of antibody
      sequences in HIV-infected individuals will be limited in their interpretation and
      predictive ability. 

PMID- 26194759
TI  - Trade-offs in antibody repertoires to complex antigens.
AB  - Pathogens vary in their antigenic complexity. While some pathogens such as
      measles present a few relatively invariant targets to the immune system, others
      such as malaria display considerable antigenic diversity. How the immune response
      copes in the presence of multiple antigens, and whether a trade-off exists
      between the breadth and efficacy of antibody (Ab)-mediated immune responses, are
      unsolved problems. We present a theoretical model of affinity maturation of B
      cell receptors (BCRs) during a primary infection and examine how variation in the
      number of accessible antigenic sites alters the Ab repertoire. Naive B cells with
      randomly generated receptor sequences initiate the germinal centre (GC) reaction.
      The binding affinity of a BCR to an antigen is quantified via a genotype
      phenotype map, based on a random energy landscape, that combines local and
      distant interactions between residues. In the presence of numerous antigens or
      epitopes, B-cell clones with different specificities compete for stimulation
      during rounds of mutation within GCs. We find that the availability of many
      epitopes reduces the affinity and relative breadth of the Ab repertoire. Despite
      the stochasticity of somatic hypermutation, patterns of immunodominance are
      strongly shaped by chance selection of naive B cells with specificities for
      particular epitopes. Our model provides a mechanistic basis for the diversity of
      Ab repertoires and the evolutionary advantage of antigenically complex pathogens.

PMID- 26194762
TI  - The new science of ageing.

PMID- 26194761
TI  - Masking of antigenic epitopes by antibodies shapes the humoral immune response to
      influenza.
AB  - The immune responses to influenza, a virus that exhibits strain variation, show
      complex dynamics where prior immunity shapes the response to the subsequent
      infecting strains. Original antigenic sin (OAS) describes the observation that
      antibodies to the first encountered influenza strain, specifically antibodies to
      the epitopes on the head of influenza's main surface glycoprotein, haemagglutinin
      (HA), dominate following infection with new drifted strains. OAS suggests that
      responses to the original strain are preferentially boosted. Recent studies also
      show limited boosting of the antibodies to conserved epitopes on the stem of HA,
      which are attractive targets for a 'universal vaccine'. We develop multi-epitope
      models to explore how pre-existing immunity modulates the immune response to new
      strains following immunization. Our models suggest that the masking of antigenic
      epitopes by antibodies may play an important role in describing the complex
      dynamics of OAS and limited boosting of antibodies to the stem of HA. Analysis of
      recently published data confirms model predictions for how pre-existing
      antibodies to an epitope on HA decrease the magnitude of boosting of the antibody
      response to this epitope following immunization. We explore strategies for
      boosting of antibodies to conserved epitopes and generating broadly protective
      immunity to multiple strains. 

PMID- 26194763
TI  - Direct and immune-mediated cytotoxicity of interleukin-21 contributes to
      antitumor effects in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma
      characterized by overexpression of cyclin D1 in 95% of patients. MCL patients
      experience frequent relapses resulting in median survival of 3 to 5 years,
      requiring more efficient therapeutic regimens. Interleukin (IL)-21, a member of
      the IL-2 cytokine family, possesses potent antitumor activity against a variety
      of cancers not expressing the IL-21 receptor (IL-21R) through immune activation.
      Previously, we established that IL-21 exerts direct cytotoxicity on IL-21R
      expressing diffuse large B-cell lymphoma cells. Herein, we demonstrate that IL-21
      possesses potent cytotoxicity against MCL cell lines and primary tumors. We
      identify that IL-21-induced direct cytotoxicity is mediated through signal
      transducer and activator of transcription 3-dependent cMyc upregulation,
      resulting in activation of Bax and inhibition of Bcl-2 and Bcl-XL. IL-21-mediated
      cMyc upregulation is only observed in IL-21-sensitive cells. Further, we
      demonstrate that IL-21 leads to natural killer (NK)-cell-dependent lysis of MCL
      cell lines that were resistant to direct cytotoxicity. In vivo treatment with IL
      21 results in complete FC-muMCL1 tumor regression in syngeneic mice via NK- and T
      cell-dependent mechanisms. Together, these data indicate that IL-21 has potent
      antitumor activity against MCL cells via direct cytotoxic and indirect, immune
      mediated effects. 

PMID- 26194764
TI  - Cladribine and cytarabine in refractory multisystem Langerhans cell
      histiocytosis: results of an international phase 2 study.
AB  - An international phase 2 study combining cladribine and cytarabine (Ara-C) was
      initiated for patients with refractory, risk-organ-positive Langerhans cell
      histiocytosis (LCH) in 2005. The protocol, comprising at least two 5-day courses
      of Ara-C (1 g/m(2) per day) plus cladribine (9 mg/m(2) per day) followed by
      maintenance therapy, was administered to 27 patients (median age at diagnosis,
      0.7 years; median follow-up, 5.3 years). At inclusion, all patients were
      refractory after at least 1 course of vinblastine (VBL) plus corticosteroid, all
      had liver and spleen involvement, and 25 patients had hematologic cytopenia.
      After 2 courses, disease status was nonactive (n = 2), better (n = 23), or stable
      (n = 2), with an overall response rate of 92%. Median disease activity scores
      decreased from 12 at the start of therapy to 3 after 2 courses (P < .0001).
      During maintenance therapy, 4 patients experienced reactivation in risk organs.
      There were 4 deaths; 2 were related to therapy toxicity and 2 were related to
      reactivation. All patients experienced severe toxicity, with World Health
      Organization grade 4 hematologic toxicity and 6 documented severe infections. The
      overall 5-year survival rate was 85% (95% confidence interval, 65.2%-94.2%).
      Thus, the combination of cladribine/Ara-C is effective therapy for refractory
      multisystem LCH but is associated with high toxicity. 

PMID- 26194765
TI  - Lectin binding to surface Ig variable regions provides a universal persistent
      activating signal for follicular lymphoma cells.
AB  - The vast majority of cases of follicular lymphoma (FL), but not normal B cells,
      acquire N-glycosylation sites in the immunoglobulin variable regions during
      somatic hypermutation. Glycans added to sites are unusual in terminating at high
      mannoses. We showed previously that the C-type lectins, dendritic cell-specific
      intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) and mannose
      receptor, bound to FL surface immunoglobulin (sIg), generating an intracellular
      Ca(2+) flux. We have now mapped further intracellular pathways activated by DC
      SIGN in a range of primary FL cells with detection of phosphorylated ERK1/2, AKT,
      and PLCgamma2. The SYK inhibitor (tamatinib) or the BTK inhibitor (ibrutinib)
      each blocked phosphorylation. Activation by DC-SIGN occurred in both IgM(+) and
      IgG(+) cases and led to upregulation of MYC expression, with detection in vivo
      observed in lymph nodes. Unlike cells of chronic lymphocytic leukemia, FL cells
      expressed relatively high levels of sIg, unchanged by long-term incubation in
      vitro, indicating no antigen-mediated downregulation in vivo. In contrast,
      expression of CXCR4 increased in vitro. Engagement of sIg in FL cells or normal B
      cells by anti-Ig led to endocytosis in vitro as expected, but DC-SIGN, even when
      cross-linked, did not lead to significant endocytosis of sIg. These findings
      indicate that lectin binding generates signals via sIg but does not mediate
      endocytosis, potentially maintaining a supportive antigen-independent signal in
      vivo. Location of DC-SIGN in FL tissue revealed high levels in sinusoidlike
      structures and in some colocalized mononuclear cells, suggesting a role for
      lectin-expressing cells at this site. 

PMID- 26194766
TI  - Therapeutic targeting of N-cadherin is an effective treatment for multiple
      myeloma.
AB  - Elevated expression of the cell adhesion molecule N-cadherin (cadherin 2, type 1,
      N-cadherin (neuronal); CDH2) is associated with poor prognosis in newly-diagnosed
      multiple myeloma (MM) patients. In this study, we investigated whether targeting
      of N-cadherin represents a potential treatment for the ~50% of MM patients with
      elevated N-cadherin. Initially, we stably knocked-down N-cadherin in the mouse MM
      plasma cell (PC) line 5TGM1 to assess the functional role of N-cadherin in MM
      pathogenesis. When compared with 5TGM1-scramble-shRNA cells, 5TGM1-Cdh2-shRNA
      cells had significantly reduced adhesion to bone marrow endothelial cells.
      However, N-cadherin knock-down did not affect 5TGM1 cell proliferation or
      adhesion to bone marrow stromal cells. In the C57BL/KaLwRij murine MM model, mice
      intravenously inoculated with 5TGM1-Cdh2-shRNA cells showed significantly
      decreased tumour burden after 4 weeks, compared with animals bearing 5TGM1
      scramble-shRNA cells. Finally, the N-cadherin antagonist ADH-1 had no effect on
      tumour burden in the established disease setting, whereas up-front ADH-1
      treatment resulted in significantly reduced tumour burden after 4 weeks. Our
      findings demonstrate that N-cadherin may play a key role in the extravasation of
      circulating MM PCs promoting bone marrow homing. Moreover, these studies suggest
      that N-cadherin may represent a viable therapeutic target to prevent the
      dissemination of MM PCs and delay MM disease progression.

PMID- 26194767
TI  - A Bayesian approach to estimating causal vaccine effects on binary post-infection
      outcomes.
AB  - To estimate causal effects of vaccine on post-infection outcomes, Hudgens and
      Halloran (2006) defined a post-infection causal vaccine efficacy estimand VEI
      based on the principal stratification framework. They also derived closed forms
      for the maximum likelihood estimators of the causal estimand under some
      assumptions. Extending their research, we propose a Bayesian approach to
      estimating the causal vaccine effects on binary post-infection outcomes. The
      identifiability of the causal vaccine effect VEI is discussed under different
      assumptions on selection bias. The performance of the proposed Bayesian method is
      compared with the maximum likelihood method through simulation studies and two
      case studies - a clinical trial of a rotavirus vaccine candidate and a field
      study of pertussis vaccination. For both case studies, the Bayesian approach
      provided similar inference as the frequentist analysis. However, simulation
      studies with small sample sizes suggest that the Bayesian approach provides
      smaller bias and shorter confidence interval length.

PMID- 26194768
TI  - Amphibious auditory evoked potentials in four North American Testudines genera
      spanning the aquatic-terrestrial spectrum.
AB  - Animals exhibit unique hearing adaptations in relation to the habitat media in
      which they reside. This study was a comparative analysis of auditory
      specialization in relation to habitat medium in Testudines, a taxon that includes
      both highly aquatic and fully terrestrial members. Evoked potential audiograms
      were collected in four species groups representing diversity along the aquatic
      terrestrial spectrum: terrestrial and fossorial Gopherus polyphemus, terrestrial
      Terrapene carolina carolina, and aquatic Trachemys scripta and Sternotherus (S.
      odoratus and S. minor). Additionally, underwater sensitivity was tested in T. c.
      carolina, T. scripta, and Sternotherus with tympana submerged just below the
      water surface. In aerial audiograms, T. c. carolina were most sensitive, with
      thresholds 18 dB lower than Sternotherus. At 100-300 Hz, thresholds in T. c.
      carolina, G. polyphemus, and T. scripta were similar to each other. At 400-800
      Hz, G. polyphemus thresholds were elevated to 11 dB above T. c. carolina. The
      underwater audiograms of T. c. carolina, T. scripta, and Sternotherus were
      similar. The results suggest aerial hearing adaptations in emydids and high
      frequency hearing loss associated with seismic vibration detection in G.
      polyphemus. The underwater audiogram of T. c. carolina could reflect retention of
      ancestral aquatic auditory function.

PMID- 26194770
TI  - Treatment of the nasal abnormalities of Hallermann-Streiff syndrome by
      lipofilling.
AB  - Hallermann-Streiff syndrome (HSS) is a rare congenital abnormality affecting
      mostly the head and face area. Craniofacial deformities, which are present in 98
      99% of cases, are the principal abnormalities detected. We focus here on a
      particular subset of these deformities: atrophy of the skin of the centre of the
      face and nose. Two patients diagnosed with HSS were treated in our department.
      Both patients underwent nasal lipofilling to treat the atrophy of the nasal skin,
      as described by Nguyen et al. In both cases, a satisfactory improvement in nasal
      skin colour and texture was observed. A functional gain was also reported by the
      parents and observed during follow-up consultations. Lipofilling thus appears to
      be an excellent option for treating craniofacial deformities in children.

PMID- 26194769
TI  - Diode laser surgery versus scalpel surgery in the treatment of fibrous
      hyperplasia: a randomized clinical trial.
AB  - Fibrous hyperplasia is treated by surgical incision using a scalpel, together
      with removal of the source of chronic trauma. However, scalpel techniques do not
      provide the haemostasis that is necessary when dealing with highly vascular
      tissues. Diode laser surgery can be used in the management of oral tissues due to
      its high absorption by water and haemoglobin, and has provided good results in
      both periodontal surgery and oral lesions. The aim of the present study was to
      compare the effects of diode laser surgery to those of the conventional technique
      in patients with fibrous hyperplasia. A randomized clinical trial was performed
      in which surgical and postoperative evaluations were analyzed. On comparison of
      the laser-treated (study group) patients to those treated with a scalpel (control
      group), significant differences were observed in the duration of surgery and the
      use of analgesic medications. Over a 3-week period, clinical healing of the
      postoperative wound was significantly faster in the control group as compared to
      the study group. In conclusion, diode laser surgery proved to be more effective
      and less invasive when compared to scalpel surgery in the management of fibrous
      hyperplasia. However, wound healing proved to be faster when using scalpel
      surgery. 

PMID- 26194771
TI  - Evaluation of single implants placed in the posterior mandibular area under
      immediate loading: a prospective study.
AB  - The aim of this study was to evaluate the survival of single dental implants
      subjected to immediate function. Twelve patients with edentulous areas in the
      posterior mandible were included in the study. All received at least one regular
      platform dental implant (3.75mm*11mm or 3.75mm*13mm). Clinical and radiographic
      parameters were evaluated. The survival rate after 12 months was 83.3%. The
      implants showed no clinical mobility, had implant stability quotient values (ISQ;
      Osstell) around 70, bone loss of up to 2mm, and a probing depth of <=3mm.
      Although the posterior mandible is an area in which the immediate loading of
      dental implants should be performed with caution, this treatment presented a good
      success rate in the present study sample. 

PMID- 26194772
TI  - Correction of facial asymmetry associated with vertical maxillary excess and
      mandibular prognathism by combined orthognathic surgery and guiding templates and
      splints fabricated by rapid prototyping technique.
AB  - The facial asymmetry associated with vertical maxillary excess and mandibular
      prognathism is one of the more complicated types in the field of oral and
      maxillofacial surgery. The purpose of this study was to investigate the efficacy
      of combined orthognathic surgeries, together with guiding templates and splints
      fabricated by rapid prototyping technique, for the correction of facial
      asymmetry. Fourteen patients with facial asymmetry associated with vertical
      maxillary excess and mandibular prognathism were included. A maxillary Le Fort I
      osteotomy, a sagittal split ramus osteotomy on the shorter side of the face, and
      an intraoral vertical ramus osteotomy on the longer side of the face were
      performed with the aid of guiding templates and splints fabricated by rapid
      prototyping technique. Parameters reflecting maxillary canting, ramal
      inclination, mandibular deviation, and chin inclination were measured before
      surgery, 7 days after surgery, and 1 year after surgery, and compared.
      Significant differences in these parameters were found between the two sides
      preoperatively, whereas no differences were observed postoperatively. Facial
      asymmetry was corrected in all patients with satisfactory outcomes. In
      conclusion, combined orthognathic surgery and guiding templates and splints can
      offer improvements in accuracy, complexity, and duration over traditional
      procedures for the correction of facial asymmetry associated with vertical
      maxillary excess and mandibular prognathism. 

PMID- 26194773
TI  - Strain induced in the condyle by self-tapping screws in the Biomet alloplastic
      temporomandibular joint: a preliminary experimental study.
AB  - The main aim of this study was to analyze how screws affect the strain
      concentration induced on the mandibular condyle during implantation, screwing,
      and drilling, as well as after condylar loading. A clean cadaveric mandible was
      analyzed experimentally in the intact state and was then implanted with a
      Biomet/Lorenz Microfixation temporomandibular joint (TMJ) implant with seven
      bicortical self-tapping screws. The external surface of the mandible was
      instrumented with three strain gauges. A load of 500N on the TMJ was applied to
      the condyle before and after implantation. The results showed a strain
      concentration of -1500MUE near the screws due to their implantation on the
      external surface of the mandible. The drilling process induced up to 80MUE near
      the hole. The strain concentration did not change when there were more than six
      screws. Loading on the TMJ before and after implantation presented only a 10%
      difference in maximum principal strain. This study demonstrates the importance of
      the strain concentration induced by the screws. The process of implanting screws
      shows the importance of lateral surface preparation for a good fit in the
      condyle. Strain distribution after implantation and loading of the Biomet implant
      was found to be similar to that in the intact condyle. 

PMID- 26194774
TI  - Temporomandibular joint osteoarthritis: cone beam computed tomography findings,
      clinical features, and correlations.
AB  - The aim of this study was to determine the prevalence of and associations between
      clinical signs and symptoms and cone beam computed tomography (CBCT) findings of
      temporomandibular joint osteoarthritis (TMJ-OA). Seventy-six patients (total 117
      TMJ) with osteoarthritis were included in this study. Clinical signs and symptoms
      and CBCT findings were reviewed retrospectively. A considerable decrease in
      mandibular motions and mastication efficiency, and considerable increase in joint
      sounds and general pain complaints were observed. The most frequent condylar bony
      changes were erosion (110 joints, 94.0%), followed by flattening (108 joints,
      92.3%), osteophytes (93 joints, 79.5%), hypoplasia (22 joints, 18.8%), sclerosis
      (14 joints, 12.0%), and subchondral cyst (four joints, 3.4%). Flattening of the
      articular eminence and pneumatization were each observed in five joints. Forty
      one patients had bilateral degeneration and 35 had unilateral degeneration.
      Hypermobility was detected in 47 degenerative joints. Masticatory efficiency was
      negatively correlated with both condylar flattening and sclerosis, and general
      pain complaints was positively correlated with condylar flattening. Condylar
      erosion, flattening, osteophytes, pain, joint sounds, reduced jaw movements, and
      worsened mastication were common findings in TMJ-OA in the present study. Poor
      correlations were found between osseous changes and clinical signs and symptoms
      of TMJ-OA. CBCT is a powerful diagnostic tool for the diagnosis of TMJ-OA.

PMID- 26194775
TI  - Dependence of cytokine levels on the sex of experimental animals: a pilot study
      on the effect of oestrogen in the temporomandibular joint synovial tissues.
AB  - The aim of this study was to evaluate the effects of 17beta-oestradiol (E2) on
      cartilage thickness and cytokine levels in the temporomandibular joint (TMJ).
      Thirty rats (15 female, 15 male) were orchidectomized (ORX), ovariectomized
      (OVX), or sham-operated. After 21 days, animals were assigned to six groups: (1)
      sham-ORX; (2) ORX; (3) ORX+E2; (4) sham-OVX; (5) OVX; and (6) OVX+E2. Treatments
      were administered daily for 21 days. The thickness of cartilage layers (fibrous,
      proliferative, maturation, and hypertrophic) and cytokine levels (interleukins IL
      1alpha, IL-1beta, IL-6, and tumour necrosis factor alpha (TNF-alpha)) were
      measured by histomorphometry and ELISA, respectively. Kruskal-Wallis/Dunn's tests
      were used (alpha=5%). Sham-ORX showed thicker layers than ORX+E2, but not thicker
      than ORX. All layers, except the hypertrophic layer, were thicker in sham-OVX
      than OVX or OVX+E2. Although IL-1beta levels were higher in castrated animals, E2
      did not affect the level of this cytokine. IL-1alpha levels were higher in both
      ORX (P=0.0010) and ORX+E2 (P=0.0053) than in sham-ORX. However, E2 decreased IL
      1alpha levels in OVX (P=0.0129). When compared to sham-ORX/OVX, IL-6 levels were
      not affected by E2 in males but were reduced in OVX (P=0.0079) and increased in
      OVX+E2 (P=0.0434). Levels of TNF-alpha were reduced by E2 in both ORX+E2 and
      OVX+E2. E2 treatment caused gender- and layer-dependent changes in the cartilage.
      Castration increased all cytokine levels, except for IL-6, without respect to
      gender. 

PMID- 26194776
TI  - Effect of statins on preventing infectious complications after surgery:
      Systematic review and meta-analysis.
AB  - OBJECTIVE: *These authors contributed equally to this work.A meta-analysis to
      investigate the association between preoperative statin use and the risk of
      postoperative infectious complications in patients undergoing surgery. METHODS:
      PubMed((r)) and Embase((r)) databases were searched for relevant studies. Data
      were extracted using a standardized data collection form. The primary effect
      measure was the odds ratio (OR) of postoperative infectious complications.
      Summary OR were calculated. RESULTS: The analysis included 10 cohort studies with
      a total of 147 263 participants. Statin use was associated with a lower incidence
      of postoperative infectious complications in all studies (summary OR 0.917, 95%
      confidence intervals [CI] 0.862, 0.975, fixed-effects model; summary OR 0.731,
      95% CI 0.584, 0.870, random-effects model); cardiac surgery (summary OR 0.673;
      95% CI 0.535, 0.847); treatment in the USA (summary OR 0.678; 95% CI 0.597,
      0.770); retrospective cohort studies (summary OR 0.664; 95% CI 0.521, 0.846).
      CONCLUSION: Preoperative statin use is associated with a reduced risk of
      postoperative infectious complications.

PMID- 26194778
TI  - Perspectives on Breast Health Education and Services Among Recent Hispanic
      Immigrant Women in the Midwest: a Qualitative Study in Lancaster County,
      Nebraska.
AB  - Breast cancer is the most common cause of cancer death among Hispanic women in
      the USA. Throughout the country, Hispanic immigrants face many barriers to
      achieving optimal breast health. Three focus groups were conducted to explore
      challenges and opportunities in access to breast health services and information
      among recent Hispanic immigrant women in Lancaster Country, Nebraska. Respondents
      perceived breast cancer as a serious issue and were concerned about it, but there
      were few cues to action to improve health given the limited information and
      access to services available to low-income Spanish-speaking individuals in the
      community. Results highlighted the need for culturally and linguistically
      appropriate health education and services, accessibility and promotion of low
      cost screening and treatment services, and inclusive policies to promote
      preventative healthcare services for all women regardless of immigration status.
      Health is more than just clinical care, and therefore, it is important to
      understand the contextual and cultural factors that have resulted in low
      screening rates and develop methods to address these them. Failure to address
      these aspects of social determinants of health could hamper efforts to improve
      breast health and reduce disparities.

PMID- 26194777
TI  - Sun Protection Belief Clusters: Analysis of Amazon Mechanical Turk Data.
AB  - This study aimed (i) to determine whether people could be differentiated on the
      basis of their sun protection belief profiles and individual characteristics and
      (ii) explore the use of a crowdsourcing web service for the assessment of sun
      protection beliefs. A sample of 500 adults completed an online survey of sun
      protection belief items using Amazon Mechanical Turk. A two-phased cluster
      analysis (i.e., hierarchical and non-hierarchical K-means) was utilized to
      determine clusters of sun protection barriers and facilitators. Results yielded
      three distinct clusters of sun protection barriers and three distinct clusters of
      sun protection facilitators. Significant associations between gender, age, sun
      sensitivity, and cluster membership were identified. Results also showed an
      association between barrier and facilitator cluster membership. The results of
      this study provided a potential alternative approach to developing future sun
      protection promotion initiatives in the population. Findings add to our knowledge
      regarding individuals who support, oppose, or are ambivalent toward sun
      protection and inform intervention research by identifying distinct subtypes that
      may best benefit from (or have a higher need for) skin cancer prevention efforts.

PMID- 26194779
TI  - Multiscale modelling of DNA mechanics.
AB  - Mechanical properties of DNA are important not only in a wide range of biological
      processes but also in the emerging field of DNA nanotechnology. We review some of
      the recent developments in modeling these properties, emphasizing the multiscale
      nature of the problem. Modern atomic resolution, explicit solvent molecular
      dynamics simulations have contributed to our understanding of DNA fine structure
      and conformational polymorphism. These simulations may serve as data sources to
      parameterize rigid base models which themselves have undergone major development.
      A consistent buildup of larger entities involving multiple rigid bases enables us
      to describe DNA at more global scales. Free energy methods to impose large
      strains on DNA, as well as bead models and other approaches, are also briefly
      discussed. 

PMID- 26194780
TI  - Ways of Hoping: Navigating the Paradox of Hope and Despair in Chronic Pain.
AB  - In this paper, we explore hope in the context of living with chronic pain.
      Individuals with chronic pain from temporomandibular disorder(s) were interviewed
      four to five times over the course of their 18-month participation in a clinical
      trial investigating the effectiveness of Traditional Chinese Medicine. We sought
      to understand shifts in participants' descriptions of expectations and
      hopefulness, particularly with regard to the work involved in counterbalancing
      positive thinking with buffers against disappointment. We found hope to be a
      dynamic and multifaceted mindset as distinct from being a single entity to be
      measured. Drawing upon Polanyi's concept of tacit knowing, we explore how
      different ways of hoping emerge and index one another in participant narratives.
      We offer a working typology of hope and raise as an issue the manner in which the
      paradox of hope--hoping enough to carry on while keeping hopes in check to avoid
      the ever-present possibility of despair--complicates simplistic notions of the
      relationship between positive thinking and the placebo response.

PMID- 26194782
TI  - Computational screening for effective Ge1-xSix nanowire photocatalyst.
AB  - We perform a comprehensive mapping of GeSi nanowire (NW) electronic band
      characteristics versus the alloy composition and the diameter (up to 3 nm) using
      hybrid density functional theory (DFT) calculations, the cluster expansion method
      and Monte Carlo simulations. We reveal that stable alloy GeSi NW configurations
      across compositions tend to exhibit asymmetric core-shell structures, which
      enhance spatial separation of the band edges, making them more effective for
      electron-hole charge separation as compared to conventional symmetric core-shell
      structures. More importantly, from the composition-size map of the NW band edges,
      we show that GeSi NWs with diameters below 3 nm are thermodynamically capable of
      photocatalysing water-splitting reactions (alkaline conditions) and CO2
      reduction. In particular, NWs with diameters of 2 and 3 nm possess desirable
      properties for efficient photo-conversion; their bandgaps (1.4 to 2.0 eV) match
      well with the solar spectrum. 

PMID- 26194783
TI  - "I felt for a long time like everything beautiful in me had been taken out":
      Women's suffering, remembering, and survival following the loss of child custody.
AB  - BACKGROUND: Child Protective Services' (CPS) placements of children in out-of
      home care disproportionately impact families marginalized by poverty, racism and
      criminalization. CPS' mandate to protect children from neglect and abuse is
      frequently criticized as failing to address the multiple social and structural
      domains shaping parents' lives, especially mothers. METHODS: We conducted a
      thematic narrative analysis of in-depth interviews to explore the impact of child
      custody loss on 19 women who use drugs residing in Toronto, Canada. We also
      assessed the potential roles of intersectional forms of violence and inequities
      in power that can both give rise to child custody loss and mediate its
      consequences. RESULTS: Trauma was identified as a key impact of separation,
      further exacerbated by women's cumulative trauma histories and ongoing mother
      child apartness. Women described this trauma as unbearable and reported
      persistent symptoms of post-traumatic stress disorder and other mental health
      conditions. Practices of dissociation through increased use of drugs and alcohol
      were central in tending to the pain of separation, and were often synergistically
      reinforced by heightened structural vulnerability observed in increased exposure
      to housing instability, intimate partner violence, and initiation of injection
      drug use and sex work. Women's survival hinged largely on hopefulness of
      reuniting with children, a goal pivotal to their sense of future and day-to-day
      intentions toward ameliorated life circumstances. CONCLUSION: Findings highlight
      needs for strategies addressing women's health and structural vulnerability
      following custody loss and also direct attention to altering institutional
      processes to support community-based alternatives to parent-child separation.

PMID- 26194781
TI  - Carbohydrate scaffolds as glycosyltransferase inhibitors with in vivo
      antibacterial activity.
AB  - The rapid rise of multi-drug-resistant bacteria is a global healthcare crisis,
      and new antibiotics are urgently required, especially those with modes of action
      that have low-resistance potential. One promising lead is the liposaccharide
      antibiotic moenomycin that inhibits bacterial glycosyltransferases, which are
      essential for peptidoglycan polymerization, while displaying a low rate of
      resistance. Unfortunately, the lipophilicity of moenomycin leads to unfavourable
      pharmacokinetic properties that render it unsuitable for systemic administration.
      In this study, we show that using moenomycin and other glycosyltransferase
      inhibitors as templates, we were able to synthesize compound libraries based on
      novel pyranose scaffold chemistry, with moenomycin-like activity, but with
      improved drug-like properties. The novel compounds exhibit in vitro inhibition
      comparable to moenomycin, with low toxicity and good efficacy in several in vivo
      models of infection. This approach based on non-planar carbohydrate scaffolds
      provides a new opportunity to develop new antibiotics with low propensity for
      resistance induction. 

PMID- 26194784
TI  - Incidence and persistence of carcinogenic genital human papillomavirus infections
      in young women with or without Chlamydia trachomatis co-infection.
AB  - We assessed whether infection with chlamydia increases the incidence of
      carcinogenic human papillomavirus (HPV) infections and if HPV persistence is
      affected by chlamydia co-infection. For 1982 women (16-29 years-old)
      participating in two consecutive rounds of a chlamydia screening implementation
      trial, swabs were polymerase chain reaction tested to detect chlamydia and 14
      carcinogenic HPV genotypes. HPV type-specific incidence and persistence rates
      were stratified for chlamydia positivity at follow-up. Associations were assessed
      by multilevel logistic regression analyses with correction for sexual risk
      factors. HPV type-specific incidence ranged from 1.4% to 8.9% and persistence
      from 22.7% to 59.4% after a median follow-up of 11 months (interquartile range:
      11-12). Differences in 1-year HPV persistence rates between chlamydia -infected
      and noninfected women were less distinct than differences in HPV incidence rates
      (pooled adjusted odds ratios of 1.17 [95% CI: 0.69-1.96] and 1.84 [95% CI: 1.36
      2.47], respectively). The effect of chlamydia co-infection on HPV-infection risk
      did not significantly differ by HPV genotype. In conclusion, infection with
      chlamydia increases the risk of infection by carcinogenic HPV types and may
      enhance persistence of some HPV types. Although these findings could reflect
      residual confounding through unobserved risk factors, our results do give reason
      to explore more fully the association between chlamydia and HPV type-specific
      acquisition and persistence.

PMID- 26194785
TI  - Synthesis of N-Sulfonylamidated and Amidated Azobenzenes under Rhodium Catalysis.
AB  - The rhodium(III)-catalyzed ortho-C-H amidation of azobenzenes with arylsulfonyl
      and aryl and alkyl isocyanates is described. The N-sulfonyl amidation reaction
      using arylsulfonyl isocyanates is first reported in the C-H activation strategy.
      These transformations provide the facile and efficient construction of a range of
      amide moieties into azobenzenes. 

PMID- 26194786
TI  - DNA-fueled molecular machine enables enzyme-free target recycling amplification
      for electronic detection of microRNA from cancer cells with highly minimized
      background noise.
AB  - The variations in microRNA (miRNA) expression levels can be useful biomarkers for
      the diagnosis of different cancers. In this work, on the basis of a new miRNA
      triggered molecular machine for enzyme-free target recycling signal
      amplification, the development of a simple electronic sensor for highly sensitive
      detection of miRNA-21 from human breast cancer cells is described. The three
      stand DNA duplex probes are self-assembled on the gold electrode surface to
      fabricate the sensor. The miRNA-21 target binds to the terminal toehold region of
      the probes, displaces one of the short strands through toehold-mediated strand
      displacement reactions, and exposes the secondary toehold region for subsequent
      hybridization with the methylene blue (MB)-modified DNA fuel strand, which
      further displaces both the miRNA-21 target and the other short strand to activate
      the operation of the molecular machine. As a result, the miRNA-21 target is
      cyclically reused, and many MB-DNA fuel strands are attached to the sensor
      surface, leading to a significantly amplified current response for sensitive
      detection of miRNA-21 down to 1.4 fM. The developed sensor also shows high
      sequence discrimination capability and can be used to monitor miRNA-21 expression
      levels in cancer cells. Moreover, this sensor avoids the involvement of any
      enzymes for target recycling amplification and features with highly minimized
      background noise for miRNA detection, which makes this method hold great
      potential for convenient monitoring of different miRNA biomarkers for early
      diagnosis of various cancers. 

PMID- 26194788
TI  - omega-Transaminases for the amination of functionalised cyclic ketones.
AB  - The potential of a number of enantiocomplementary omega-transaminases (omega
      TAms) in the amination of cyclic ketones has been investigated. After a
      preliminary screening of several compounds with increasing complexity, different
      approaches to shift the equilibrium of the reaction to the amine products were
      studied, and reaction conditions (temperature and pH) optimised. Interestingly, 2
      propylamine as an amine donor was tolerated by all five selected omega-TAms, and
      therefore used in further experiments. Due to the higher conversions observed and
      interest in chiral amines studies then focused on the amination of alpha
      tetralone and 2-methylcyclohexanone. Both ketones were aminated to give the
      corresponding amine with at least one of the employed enzymes. Moreover, the
      amination of 2-methylcyclohexanone was investigated in more detail due to the
      different stereoselectivities observed with TAms used. The highest yields and
      stereoselectivities were obtained using the omega-TAm from Chromobacterium
      violaceum (CV-TAm), producing 2-methylcyclohexylamine with complete
      stereoselectivity at the (1S)-amine position and up to 24 : 1 selectivity for the
      cis : trans [(1S,2R) : (1S,2S)] isomer. 

PMID- 26194787
TI  - Characterizing the Processes for Navigating Internet Health Information Using
      Real-Time Observations: A Mixed-Methods Approach.
AB  - BACKGROUND: Little is known about the processes people use to find health-related
      information on the Internet or the individual characteristics that shape
      selection of information-seeking approaches. OBJECTIVE: Our aim was to describe
      the processes by which users navigate the Internet for information about a
      hypothetical acute illness and to identify individual characteristics predictive
      of their information-seeking strategies. METHODS: Study participants were
      recruited from public settings and agencies. Interested individuals were screened
      for eligibility using an online questionnaire. Participants listened to one of
      two clinical scenarios-consistent with influenza or bacterial meningitis-and then
      conducted an Internet search. Screen-capture video software captured Internet
      search mouse clicks and keystrokes. Each step of the search was coded as
      hypothesis testing (etiology), evidence gathering (symptoms), or action/treatment
      seeking (behavior). The coded steps were used to form a step-by-step pattern of
      each participant's information-seeking process. A total of 78 Internet health
      information seekers ranging from 21-35 years of age and who experienced barriers
      to accessing health care services participated. RESULTS: We identified 27 unique
      patterns of information seeking, which were grouped into four overarching
      classifications based on the number of steps taken during the search, whether a
      pattern consisted of developing a hypothesis and exploring symptoms before ending
      the search or searching an action/treatment, and whether a pattern ended with
      action/treatment seeking. Applying dual-processing theory, we categorized the
      four overarching pattern classifications as either System 1 (41%, 32/78),
      unconscious, rapid, automatic, and high capacity processing; or System 2 (59%,
      46/78), conscious, slow, and deliberative processing. Using multivariate
      regression, we found that System 2 processing was associated with higher
      education and younger age. CONCLUSIONS: We identified and classified two
      approaches to processing Internet health information. System 2 processing, a
      methodical approach, most resembles the strategies for information processing
      that have been found in other studies to be associated with higher-quality
      decisions. We conclude that the quality of Internet health-information seeking
      could be improved through consumer education on methodical Internet navigation
      strategies and the incorporation of decision aids into health information
      websites.

PMID- 26194789
TI  - A Long Neglected Damper in the El Nino--Typhoon Relationship: a 'Gaia-Like'
      Process.
AB  - Proposed in the early 1970's, the Gaia hypothesis suggests that our planet earth
      has a self-regulating ability to maintain a stable condition for life. Tropical
      cyclone (TC) is one of the earth's most hazardous disasters; it is intriguing to
      explore whether 'Gaia-like' processes may exist in nature to regulate TC
      activities. El Nino can shift the forming position of the Western Pacific
      typhoons away from land. This shift enables typhoons to travel longer distances
      over ocean and is known to be a positive process to promote TCs to achieve higher
      intensity. What is neglected, however, is that there co-exists a negative
      process. Here we show that during El Nino, typhoons intensify over region
      undergoing strong ocean subsurface shoaling where upper ocean heat content can
      drop by 20-50%. This 'worsen' ocean pre-condition can effectively reduce ocean's
      energy supply for typhoon intensification during typhoon-ocean interaction. We
      find this an elegant, 'Gaia-like' process demonstrating nature's self-regulating
      ability. Though during El Nino, typhoons can take advantage of the longer
      travelling distance over ocean to achieve higher intensity, nature is also
      providing a damper to partially cancel this positive impact. Without the damper,
      the situation could be even worse. 

PMID- 26194790
TI  - Development of a novel imaging system for cell therapy in the brain.
AB  - INTRODUCTION: Stem cells have been evaluated as a potential therapeutic approach
      for several neurological disorders of the central and peripheral nervous system
      as well as for traumatic brain and spinal cord injury. Currently, the lack of a
      reliable and safe method to accurately and non-invasively locate the site of
      implantation and track the migration of stem cells in vivo hampers the
      development of stem cell therapy and its clinical application. In this report, we
      present data that demonstrate the feasibility of using the human sodium iodide
      symporter (hNIS) as a reporter gene for tracking neural stem cells (NSCs) after
      transplantation in the brain by using single-photon emission tomography/computed
      tomography (SPECT/CT) imaging. METHODS: NSCs were isolated from the hippocampus
      of adult rats (Hipp-NSCs) and transduced with a lentiviral vector containing the
      hNIS gene. Hipp-NSCs expressing the hNIS (NIS-Hipp-NSCs) were characterized in
      vitro and in vivo after transplantation in the rat brain and imaged by using
      technetium-99m ((99m)Tc) and a small rodent SPECT/CT apparatus. Comparisons were
      made between Hipp-NSCs and NIS-Hipp-NSCs, and statistical analysis was performed
      by using two-tailed Student's t test. RESULTS: Our results show that the
      expression of the hNIS allows the repeated visualization of NSCs in vivo in the
      brain by using SPECT/CT imaging and does not affect the ability of Hipp-NSCs to
      generate neuronal and glial cells in vitro and in vivo. CONCLUSIONS: These data
      support the use of the hNIS as a reporter gene for non-invasive imaging of NSCs
      in the brain. The repeated, non-invasive tracking of implanted cells will
      accelerate the development of effective stem cell therapies for traumatic brain
      injury and other types of central nervous system injury.

PMID- 26194792
TI  - JALA Special Issue: New Developments in Biosensing Technologies.

PMID- 26194791
TI  - Study protocol: a randomised controlled trial testing the effectiveness of 'Op
      Volle Kracht' in Dutch residential care.
AB  - BACKGROUND: Although adolescents are often referred to residential treatment
      centres because of severe externalizing behaviours, a vast majority demonstrated
      comorbid symptoms of depression and anxiety. Covert internalizing symptoms in
      these adolescents might be easily unrecognized and therefore untreated.
      Adolescents with mild intellectual disability (MID) are overrepresented among
      youth with both externalizing and internalizing problems. There are yet few
      treatment programs available for adolescents with both externalizing and
      internalizing problems. METHODS/DESIGN: The CBT-based resiliency program, Op
      Volle Kracht (OVK), which is based on the US Penn Resiliency Program (PRP), was
      adapted to suit the needs of adolescents with both externalizing and
      internalizing problems, either with or without MID, in Dutch residential
      treatment centres. The effectiveness of this group intervention program of eight
      sessions will be tested in a randomised controlled trial (RCT) with N = 182
      adolescents aged 12-16, allocated to either the target intervention plus
      treatment as usual (OVK + TAU) or treatment as usual only (TAU). The main outcome
      variables include depressive symptoms (primary), anxiety, behavioural problems,
      and group therapeutic climate. Cognitive styles and coping styles will be
      included as possible mediators. Assessments take place at baseline (T1), one week
      before the start of the program (T2), immediately after the program (T3), and at
      three months follow-up (T4). DISCUSSION: The program assets include its wide
      implementation possibilities due to low costs, the short duration of the program
      and the delivery by group care workers, and its suitability for adolescents with
      MID. Further strengths of the present study design include its robust method
      (RCT), the ecological validity, and the inclusion of possible mediators of
      treatment effect. The program emphasizes individual risk factors for depression
      rather than social and family factors. Implications for practice and future
      research are discussed. TRIAL REGISTRATION: Dutch Trial Register NTR4836.

PMID- 26194794
TI  - Increased efficiency in identifying mixed pollen samples by meta-barcoding with a
      dual-indexing approach.
AB  - BACKGROUND: Meta-barcoding of mixed pollen samples constitutes a suitable
      alternative to conventional pollen identification via light microscopy. Current
      approaches however have limitations in practicability due to low sample
      throughput and/or inefficient processing methods, e.g. separate steps for
      amplification and sample indexing. RESULTS: We thus developed a new primer
      adapter design for high throughput sequencing with the Illumina technology that
      remedies these issues. It uses a dual-indexing strategy, where sample-specific
      combinations of forward and reverse identifiers attached to the barcode marker
      allow high sample throughput with a single sequencing run. It does not require
      further adapter ligation steps after amplification. We applied this protocol to
      384 pollen samples collected by solitary bees and sequenced all samples together
      on a single Illumina MiSeq v2 flow cell. According to rarefaction curves, 2,000
      3,000 high quality reads per sample were sufficient to assess the complete
      diversity of 95% of the samples. We were able to detect 650 different plant taxa
      in total, of which 95% were classified at the species level. Together with the
      laboratory protocol, we also present an update of the reference database used by
      the classifier software, which increases the total number of covered global plant
      species included in the database from 37,403 to 72,325 (93% increase).
      CONCLUSIONS: This study thus offers improvements for the laboratory and
      bioinformatical workflow to existing approaches regarding data quantity and
      quality as well as processing effort and cost-effectiveness. Although only tested
      for pollen samples, it is furthermore applicable to other research questions
      requiring plant identification in mixed and challenging samples.

PMID- 26194795
TI  - Evaluation of the population structure and genetic diversity of Plasmodium
      falciparum in southern China.
AB  - BACKGROUND: Yunnan and Hainan provinces are the two major endemic regions for
      Plasmodium falciparum malaria in China. However, few studies have investigated
      the characteristics of this parasite. Therefore, this study aimed to evaluate the
      genetic diversity and population structure of P. falciparum to predict the
      geographic origin of falciparum malaria. METHODS: Thirteen highly polymorphic
      microsatellite loci were studied to estimate the genetic diversity and population
      structure of 425 P. falciparum isolates obtained from blood samples collected
      from Yunnan and Hainan provinces of South China. The isolates were analysed for
      genetic diversity, linkage disequilibrium, and population structure. The parasite
      populations were clustered into two subgroups (i.e., Yunnan and Hainan) and a
      classification algorithm was used to identify molecular markers for classifying
      the P. falciparum populations. RESULTS: All 13 microsatellite loci were highly
      polymorphic, with the number of alleles per locus varying from 5 to 20. The mean
      expected heterozygosity (He) in Yunnan and Hainan was 0.766 +/- 0.036 and 0.677
      +/- 0.039, respectively, revealing a moderate high level of genetic diversity.
      Significant linkage disequilibrium was found for some regions of Yunnan (Lazan
      county and Xishuangbanna region) and Hainan (Dongfang city and Sanya city)
      province. According to the classification algorithm, a combination of three
      microsatellites could be used as a discriminatory marker to identify the origin
      of P. falciparum isolates. CONCLUSIONS: The results on the genetic structure of
      P. falciparum populations from South China provide a basis for developing a
      genetic marker-based tool to trace the source of the parasite infections and
      consequently improve malaria control and elimination strategies.

PMID- 26194797
TI  - Preoperative hypoalbuminemia and anemia as predictors of transfusion in radical
      nephrectomy for renal cell carcinoma: a retrospective study.
AB  - BACKGROUND: The only curative therapy for renal cell carcinoma is the complete
      removal of malignant tissue. Surgical bleeding during radical nephrectomy may
      require blood transfusion. Blood transfusion, however, is associated with
      postoperative morbidity and mortality. This study investigated predictive factors
      of transfusion requirement in patients undergoing radical nephrectomy, as well as
      the effects of transfusion on postoperative outcomes. METHODS: This study
      retrospectively enrolled 526 patients who underwent open radical nephrectomy for
      renal cell carcinoma between 2010 and 2012. Univariate and multivariate logistic
      regression analyses were used to determine independent predictive factors of a
      requirement for packed red blood cell (PRBC) transfusion. Postoperative outcomes
      included an admission to the intensive care unit (ICU) and lengths of ICU and
      hospital stay. RESULTS: Of the 526 patients, 93 (17.7 %) required PRBC
      transfusion, with these patients requiring a mean 5.5 units. Preoperative
      hypoalbuminemia (serum albumin <3.5 g/dL) was observed in 75 (14.3 %) patients,
      and preoperative anemia (hemoglobin <12.0 g/dL) in 121 (23.0 %). Multivariate
      logistic regression analysis showed that preoperative hypoalbuminemia,
      preoperative anemia, and a high cancer stage were independent factors
      significantly associated with PRBC transfusion in open radical nephrectomy. The
      transfused group had higher incidence of ICU admission and longer lengths of ICU
      and hospital stay than the non-transfused group. CONCLUSIONS: Preoperative
      hypoalbuminemia and anemia are important predictors of PRBC transfusion during
      radical nephrectomy for renal cell carcinoma. Furthermore, transfusion is
      associated with poor postoperative outcomes.

PMID- 26194796
TI  - Chronic inflammation and the development of malignancy in the GI tract.
AB  - The role of immunologic factors in the development of gastrointestinal (GI)
      neoplasia, made evident from the high degree of association of chronic intestinal
      or gastric inflammation with the development of cancer, has attracted much
      attention because it promises new ways of treating disease. Here we develop the
      idea that immunologic factors influence the appearance of GI cancer on two
      levels: (i) a basic and initiating level during which the epithelial cell is
      induced to undergo pre-cancerous molecular changes that render it prone to
      further cancer progression; and (ii) a secondary level that builds on this
      vulnerability and drives the cell into frank malignancy. This secondary level is
      uniquely dependent on a single epithelial cell signaling pathway centered on
      STAT3, and it is this pathway upon which stimulation of mucosal cytokine
      production and microbiota effects converge. 

PMID- 26194798
TI  - Psychometric properties of the Drinking Motives Questionnaire-Revised among
      community-dwelling current drinkers in the Ningxia autonomous region of China.
AB  - INTRODUCTION AND AIMS: The 20-item Drinking Motives Questionnaire-Revised (DMQ-R)
      which assesses social, enhancement, coping and conformity-related motives for
      drinking-has not previously been used in China. The aim of this paper is to
      evaluate the psychometric properties of the DMQ-R in China. DESIGN AND METHODS:
      DMQ-R was administered to 612 current drinkers identified from a representative
      sample of 2425 non-institutionalised adults living in Ningxia Province, China; 44
      of these current drinkers were re-administered the questionnaire an average of
      2.5 days later. Confirmatory factor analysis compared the adequacy of fit of
      alternative conceptual models. Due to the collectivist culture in China, we
      considered the possibility that item 12 ('to fit in the group I like') is an
      indicator of a 'social' motive (in Western studies, it is an indicator of a
      'conformity' motive). RESULTS: Social motives for drinking were more frequently
      endorsed than other motives. The intraclass correlation coefficients for the test
      retest reliability of the four subscales varied from 0.63 to 0.80. The originally
      conceptualised four-factor model showed good fit to the data [root mean square
      error of approximation (RMSEA) = 0.043, comparative fit index = 0.949 and Tucker
      Lewis index = 0.941]. Fit indices improved (RSMEA = 0.034, comparative fit index
      = 0.968 and Tucker-Lewis index = 0.963) when item 12 was included in the 'social'
      dimension rather than the 'conformity' dimension. The 12-item short form of DMQ-R
      showed similar psychometric properties, but the fit indices were suboptimal.
      DISCUSSION AND CONCLUSIONS: DMQ-R is a valid and reliable tool to assess drinking
      motives among current drinkers in China. Future studies in China using the DMQ-R
      should consider item 12 a social motive. [Cheng HG, Phillips MR, Zhang Y, Wang Z.
      Psychometric properties of the Drinking Motives Questionnaire-Revised among
      community-dwelling current drinkers in the Ningxia autonomous region of China.
      Drug Alcohol Rev 2016;35:433-441].

PMID- 26194799
TI  - Isolation and characterization of primary microglia from post-natal murine brain
      tissues: a comparison of two methods.
AB  - Microglia are resident macrophages of the central nervous system (CNS). Apart
      from playing vital roles as sentinel cells, they are crucial in physiological
      processes such as synaptic pruning during brain development. CNS disorders
      require an understanding of the contribution of each cellular compartment to the
      pathogenesis. Elucidating the role of microglia in disease development and
      progression in the intricate CNS environment is technically challenging and
      requires the establishment of reliable, reproducible techniques to isolate and
      culture microglia. A number of different protocols have been developed for
      isolation of neonatal microglia and here we compare two widely used methods,
      namely, mild trypsinization and EasySep(r) magnetic separation. EasySep(r)
      magnetic separation provided higher microglia yield, and flow cytometric
      evaluation of CD11b and F4/80 markers revealed that EasySep(r) separation method
      also produced significantly higher purity compared to mild trypsinization.
      Microglia isolated using EasySep(r) separation method were functional, as
      demonstrated by the generation of nitric oxide, IL-6, TNF-alpha, and MCP-1 in
      response to lipopolysaccharide stimulation. In summary, this study has revealed
      that magnetic separation is superior to mild trypsinization in terms of yield and
      purity of microglia. 

PMID- 26194801
TI  - The role of preterm placental calcification on assessing risks of stillbirth.
AB  - INTRODUCTION: Stillbirth is an important issue in antenatal care and much remains
      unknown. This cohort study aims to explore the previously un-identified risk
      factor of third-trimester stillbirth to determine if Grade III preterm placental
      calcification (PPC) is associated with stillbirth. METHODS: At a tertiary
      teaching hospital, obstetric ultrasonography was performed at 28 weeks' gestation
      to establish a diagnosis of PPC. Pregnancies with multifetal gestations, major
      fetal congenital anomalies, termination, cord accidents, apparent intrauterine
      infection, and antepartum complications were excluded. RESULTS: 15,122 eligible
      pregnancies were categorized as stillbirth (n = 99) and livebirth (n = 15,023)
      groups. Between these two groups, there were no significant differences in
      maternal age, BMI, and parity, but significant differences in smoking and in PPC
      (35.4% vs 6.3%, p < 0.001) were observed. The peak occurrence of stillbirths was
      at 30 and 37 weeks' gestation, with a bimodal distribution of 11 and 17
      stillbirths, respectively. For pregnancies with or without PPC, the incidences of
      stillbirths per-1000-births were 35.9 and 4.5, respectively. Using Kaplan-Meier
      survival analysis, at 40 weeks' gestation the cumulative stillbirth risk for
      pregnancies with PPC was higher compared to those without PPC. Logistic
      regression revealed that after adjusting for the effects of smoking and
      demographic factors, the risk of stillbirth (adjusted OR:7.62; 95% CI:5.00-11.62)
      was much higher when PPC was present. DISCUSSION: Grade III PPC is associated
      with a higher incidence of stillbirth, and identified an independent risk factor.
      Being a pathologic implication, it may precede this negative outcome and can
      serve as a warning sign or marker when noted on ultrasonography.

PMID- 26194802
TI  - Selenocystine-induced cell apoptosis and S-phase arrest inhibit human triple
      negative breast cancer cell proliferation.
AB  - Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer
      with limited effective treatment options. New therapeutic approaches are urgently
      needed to improve the prognosis of TNBC. Here we demonstrated that a redox
      modulator, selenocystine (SeC), significantly inhibits TNBC cell proliferation in
      a dose- and time-dependent manner. Through cell apoptosis assays and cell cycle
      distribution analyses, we have shown that the in vitro inhibitory effect of SeC
      on TNBC cells can be attributed to the induction of apoptosis and the S-phase
      arrest in a dose-dependent manner. Therefore, this finding implies that SeC
      potentially is a novel therapeutic agent for TNBC. 

PMID- 26194804
TI  - Assessing the impact of including leaflets in the simulation of TAVI deployment
      into a patient-specific aortic root.
AB  - Computational simulation of transcatheter aortic valve implantation (TAVI) device
      deployment presents a significant challenge over and above similar simulations
      for percutaneous coronary intervention due to the presence of prosthetic
      leaflets. In light of the complexity of these leaflets, simulations have been
      performed to assess the effect of including the leaflets in a complete model of a
      balloon-expandable TAVI device when deployed in a patient-specific aortic root.
      Using an average model discrepancy metric, the average frame positions (with and
      without the leaflets) are shown to vary by 0.236% of the expanded frame diameter
      (26 mm). This relatively small discrepancy leads to the conclusion that for a
      broad range of replacement valve studies, including new frame configurations and
      designs, patient-specific assessment of apposition, paravalvular leakage and
      tissue stress, modelling of the prosthetic leaflets is likely to have a marginal
      effect on the results

PMID- 26194803
TI  - von Hippel-Lindau gene plays a role during zebrafish pronephros development.
AB  - von Hippel-Lindau (pVHL)-mediated ubiquitination of HIF-1alpha plays a central
      role in the cellular responses to changes in oxygen availability. In the present
      study, using zebrafish as a model, we showed that specific knockdown of
      endogenous vhl leads to pronephros malformation and renal failure. Knockdown of
      vhl resulted in abnormal kidney development, including curved and cystic
      pronephric tubule or/and cystic and atrophic glomerulus. Co-injecting capped vhl
      messenger RNA (mRNA) partially rescued pronephros morphant phenotype, confirming
      the specificity of the morpholino oligonucleotide (MO)-induced pronephric
      defects. In keeping with the pronephros phenotype, renal function was affected as
      well in vhl morphants. Dextran clearance abilities of vhl morphants were
      significantly reduced as compared with those of control embryos. Further analysis
      indicated that glomerular integrity is impaired in vhl morphants, while the
      organization of pronephric duct was minimally affected. Vhl morphants display
      global increased vegf signaling and angiogenesis. In addition, we found that vhl
      morphants displayed elevated expression of vegfa in podocytes and increased
      angiogenesis at pronephric glomerulus and the nearby vessels. Treatment of vegf
      inducer to embryos also caused pronephros phenotype resembling vhl morphants,
      further supporting that increased vegfa signaling contribute to the pronephros
      morphant phenotype. Our study establishes the zebrafish as an alternative
      vertebrate model system for studying Vhl function during kidney development. 

PMID- 26194805
TI  - Cloning and Characterization of ifitm1 and ifitm3 Expression During Early
      Zebrafish Development - CORRIGENDUM.
AB  - The authors apologise for errors in the corresponding authors details given on
      page 1 of the article. Below is the correct information of the corresponding
      author and email address : 1) Wei-Wei Xue, Huan-Nan Wang, Zhi-Meng Wang, Meng-Xi
      Qiu, Jing Che, Feng-Jiao Deng* and Jiang-Dong Liu* 2) *All correspondence to:
      Feng-Jiao Deng and Jiang-Dong Liu. e-mail: fish4@whu.edu.cn 3) All authors are
      from the same one laboratory. The second laboratory was superfluous and should be
      deleted. 

PMID- 26194806
TI  - Lipophylic Statins in Heart Failure.

PMID- 26194807
TI  - Cancer-associated TERT promoter mutations abrogate telomerase silencing.
AB  - Mutations in the human telomerase reverse transcriptase (TERT) promoter are the
      most frequent non-coding mutations in cancer, but their molecular mechanism in
      tumorigenesis has not been established. We used genome editing of human
      pluripotent stem cells with physiological telomerase expression to elucidate the
      mechanism by which these mutations contribute to human disease. Surprisingly,
      telomerase-expressing embryonic stem cells engineered to carry any of the three
      most frequent TERT promoter mutations showed only a modest increase in TERT
      transcription with no impact on telomerase activity. However, upon
      differentiation into somatic cells, which normally silence telomerase, cells with
      TERT promoter mutations failed to silence TERT expression, resulting in increased
      telomerase activity and aberrantly long telomeres. Thus, TERT promoter mutations
      are sufficient to overcome the proliferative barrier imposed by telomere
      shortening without additional tumor-selected mutations. These data establish that
      TERT promoter mutations can promote immortalization and tumorigenesis of
      incipient cancer cells. 

PMID- 26194808
TI  - Taking the brakes off telomerase.
AB  - Studies using human embryonic stem cells have revealed how common cancer
      associated mutations exert their effect on telomerase after cells differentiate
      into more specialized cell types. 

PMID- 26194809
TI  - Effects of neutropenia and histological responses in esophageal squamous cell
      carcinoma with neo-adjuvant chemotherapy.
AB  - BACKGROUND: Neo-adjuvant chemotherapy (NAC) followed by radical esophagectomy has
      been shown to prolong survival in patients with locally advanced esophageal
      squamous cell carcinoma (ESCC). However, neutropenia, one of the major adverse
      events due to NAC, influences the therapeutic course. The aim of this study is to
      clarify the relationship between neutropenia and therapeutic response in ESCC
      with NAC. METHODS: A total of 117 patients with clinical stage II/III ESCC who
      had undergone NAC followed by radical esophagectomy were retrospectively analyzed
      in terms of the relationship between neutropenia and clinicopathological features
      or outcomes. RESULTS: Neutropenia was the major adverse event observed in 56 %
      (66/117) and grade 3/4 neutropenia occurred in 29 % of patients. Grade 3/4
      neutropenia correlated with a high histological response (Grade 1b-3) (p < 0.01).
      Correlative analysis identified grade 3/4 neutropenia and poor differentiation as
      independent predictors of a high histological response (odds ratio 5.13 and 3.25,
      p < 0.01 and p = 0.01, respectively). Survival analysis showed that patients with
      a high histological response had significantly longer survival than those with a
      low histological response (Grade 0-1a) (p = 0.03), whereas no significant
      differences were found for survival according to the grade of neutropenia (p =
      0.45). In a subgroup analysis according to histological response, grade 3/4
      neutropenia correlated with worse survival in patients with a low histological
      response (p = 0.05). CONCLUSION: Severe neutropenia due to NAC correlates with a
      high histological response in ESCC. However, severe neutropenia may also result
      in a worse prognosis for patients with a low histological response.

PMID- 26194810
TI  - Strategies for dealing with fraud in clinical trials.
AB  - Research misconduct and fraud in clinical research is an increasing problem
      facing the scientific community. This problem is expected to increase due to
      discoveries in central statistical monitoring and with the increase in first-time
      clinical trial investigators in the increasingly global reach of oncology
      clinical trials. This paper explores the most common forms of fraud in clinical
      trials in order to develop offensive and defensive strategies to deal with fraud.
      The offensive strategies are used when fraud is detected during a trial and the
      defensive strategies are those design strategies that seek to minimize or
      eliminate the effect of fraud. This leads to a proposed fraud recovery plan (FRP)
      that would be specified before the start of a clinical trial and would indicate
      actions to be taken upon detecting fraud of different types.
      Statistical/regulatory issues related to fraud include: dropping all patients
      from a site that committed fraud, or just the fraudulent data (perhaps replacing
      the latter through imputation); the role of intent-to-treat analysis; effect on a
      planned interim analysis; effect on stratified analyses and model adjustment when
      fraud is detected in covariates; effect on trial-wide randomization, etc. The
      details of a typical defensive strategy are also presented. It is concluded that
      it is best to follow a defensive strategy and to have an FRP in place to follow
      if fraud is detected during the trial. 

PMID- 26194811
TI  - Revisiting the potential signs of colorectal cancer on contrast-enhanced computed
      tomography without bowel preparation.
AB  - Colorectal cancer (CRC) is the second most common cause of cancer death in the
      US. Earlier detection can allow treatment with curative intent and improve
      prognosis. Optical and virtual colonoscopy are widely used in screening for
      colonic polyps and in the investigation of suspected CRC. However, contrast
      enhanced computed tomography (CT) is still performed to investigate various non
      specific abdominal complaints. Hence, a significant number of CRC are identified
      on contrast-enhanced CT without bowel preparation. We describe several signs,
      which when present in tandem, raise suspicion of CRC, and may warrant further
      investigation with optical colonoscopy. These include an intraluminal mass,
      eccentric or circumferential wall thickening >3 mm, focal wall enhancement,
      pericolic fat stranding, a cluster of >3 local lymph nodes, and enlarged lymph
      nodes >10 mm in short axis. Multiplanar evaluation of the bowel should be
      performed on all CT abdominal studies, including those without bowel preparation,
      to identify subtle features of CRC.

PMID- 26194812
TI  - Role of imaging for patients with colorectal hepatic metastases: what the
      radiologist needs to know.
AB  - Surgical resection of colorectal metastatic disease has increased as surgeons
      have adopted a more aggressive ideology. Current exclusion criteria are patients
      for whom a negative resection margin is not feasible or a future liver remnant
      (FLR) of greater than 20% is not achievable. The goal of preoperative imaging is
      to identify the number and distribution of liver metastases, in addition to
      establishing their relation to relevant intrahepatic structures. FLR can be
      calculated utilizing cross-sectional imaging to select out patients at risk for
      hepatic dysfunction after resection. MRI, specifically with gadoxetic acid
      contrast, is currently the preferred modality for assessment of hepatic
      involvement for patients with newly diagnosed colorectal cancer, to include those
      who have undergone neoadjuvant chemotherapy. Employment of liver-directed
      therapies has recently expanded and they may provide an alternative to
      hepatectomy in order to obtain locoregional control in poor surgical candidates
      or convert patients with initially unresectable disease into surgical candidates.

PMID- 26194813
TI  - Errors in imaging the pregnant patient with acute abdomen.
AB  - Pregnant women with an acute abdomen present a critical issue due to the
      necessity for an immediate diagnosis and treatment; in fact, a diagnostic delay
      could worsen the outcome for both the mother and the fetus. There is evidence
      that emergencies during pregnancy are subject to mismanagement; however, the
      percentage of errors in the diagnosis of emergencies in pregnancy has not been
      studied in depth. The purpose of this article is to review the most common
      imaging error emergencies. The topics covered are divided into gynecological and
      non-gynecological entities and, for each pathology, possible errors have been
      dealt with in the diagnostic pathway, the possible technical errors in the exam
      execution, and finally the possible errors in the interpretation of the images.
      These last two entities are often connected owing to a substandard examination,
      which can cause errors in the interpretation. Consequently, the systemization of
      errors reduces the possibility of reoccurrences in the future by providing a
      valid approach in helping to learn from these errors. 

PMID- 26194814
TI  - Providing parents with individualised support in a neonatal intensive care unit
      reduced stress, anxiety and depression.

PMID- 26194815
TI  - Contemporary results of carotid endarterectomy in "normal-risk" patients from the
      Society for Vascular Surgery Vascular Registry.
AB  - OBJECTIVE: Acceptable complication rates after carotid endarterectomy (CEA) are
      drawn from decades-old data. The recent Carotid Revascularization Endarterectomy
      versus Stenting Trial (CREST) demonstrated improved stroke and mortality outcomes
      after CEA compared with carotid artery stenting, with 30-day periprocedural CEA
      stroke rates of 3.2% and 1.4% for symptomatic (SX) and asymptomatic (ASX)
      patients, respectively. It is unclear whether these target rates can be attained
      in "normal-risk" (NR) patients experienced outside of the trial. This study was
      done to determine the contemporary results of CEA from a broader selection of NR
      patients. METHODS: The Society for Vascular Surgery (SVS) Vascular Registry was
      examined to determine in-hospital and 30-day event rates for NR, SX, and ASX
      patients undergoing CEA. NR was defined as patients without anatomic or
      physiologic risk factors as defined by SVS Carotid Practice Guidelines. Raw data
      and risk-adjusted rates of death, stroke, and myocardial infarction (MI) were
      compared between the ASX and SX cohorts. RESULTS: There were 3977 patients (1456
      SX, 2521 ASX) available for comparison. The SX group consisted of more men (61.7%
      vs 57.0%; P = .0045) but reflected a lower proportion of white patients (91.3% vs
      94.4%; P = .0002), with lower prevalence of coronary artery disease (P < .0001),
      prior MI (P < .0001), peripheral vascular disease (P = .0017), and hypertension
      (P = .029), although New York Heart Association grade >3 congestive heart failure
      was equally present in both groups (P = .30). Baseline stenosis >80% on duplex
      imaging was less prevalent among SX patients (54.2% vs 67.8%; P < .0001).
      Perioperative stroke rates were higher for SX patients in the hospital (2.8% vs
      0.8%; P < .0001) and at 30 days (3.4% vs 1.0%; P < .0001), which contributed to
      the higher composite death, stroke, and MI rates in the hospital (3.6% vs 1.8; P
      = .0003) and at 30 days (4.5% vs 2.2%; P < .0001) observed in SX patients. After
      risk adjustment, the rate of stroke/death was greater among SX patients in the
      hospital (odds ratio, 2.05; 95% confidence interval, 1.18-3.58) although not at
      30 days (odds ratio, 1.36; 95% confidence interval, 0.85-2.17). No in-hospital or
      30-day differences were observed for death or MI by symptom status. CONCLUSIONS:
      The SVS Vascular Registry results for CEA in NR patients are similar by symptom
      status to those reported for CREST and may serve as a benchmark for comparing
      results of alternative therapies for treatment of carotid stenosis in NR patients
      outside of monitored clinical trials. The contemporary perioperative risk of
      stroke after CEA in NR patients continues to be higher for SX than for ASX
      patients.

PMID- 26194816
TI  - Endovascular treatment of thoracoabdominal aortic aneurysm using physician
      modified endografts.
AB  - OBJECTIVE: To report an initial experience with physician-modified thoracic
      endografts for endovascular treatment of thoracoabdominal aortic aneurysm (TAAA).
      METHODS: Single-center cohort study of the treatment of TAAA using a physician
      modified fenestrated thoracic endograft for patients deemed to be at high risk of
      open repair. The cohort includes 21 patients in a prospective physician-sponsored
      U.S. Food and Drug Administration-approved investigational device exemption study
      and three patients treated outside the investigational device exemption. The
      procedure involves physician modification of a Cook TX2 thoracic stent graft with
      reinforced fenestrations. Branch stents were iCast balloon expandable stents.
      Treatment success was defined as successful aneurysm exclusion with freedom from
      permanent organ system dysfunction and return to preoperative level of
      independent functional status. RESULTS: Twenty-four consecutive patients were
      treated. Twenty-one patients (88%) met the endpoint of treatment success at a
      mean of 11 months follow-up. One patient (4%) died within 30 days due to
      complications of spinal cord injury (SCI). One patient (4%) died 4 months
      postoperatively after a prolonged recovery from surgery. One other patient (4%)
      is alive 13 months after operation with permanent SCI. One renal reintervention
      has been required. No device failures have occurred. CONCLUSIONS: Early-term data
      suggest that physician-modified fenestrated thoracic endografts can be used to
      safely and effectively treat TAAA in patients at high risk of open repair.
      Physician-modified devices perform similarly to commercially manufactured grafts
      in terms of treatment success, SCI, perioperative death, and clinical outcome at
      short-term follow-up. Physician modification is immediately available and allows
      for a high level of customizability. Procedure success is contingent upon careful
      preoperative planning, patient selection, experienced providers, and a high
      volume center.

PMID- 26194817
TI  - Bacteria and archaea paleomicrobiology of the dental calculus: a review.
AB  - Dental calculus, a material observed in the majority of adults worldwide, emerged
      as a source for correlating paleomicrobiology with human health and diet. This
      mini review of 48 articles on the paleomicrobiology of dental calculus over 7550
      years discloses a secular core microbiota comprising nine bacterial phyla -
      Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, TM7, Synergistetes,
      Chloroflexi, Fusobacteria, Spirochetes - and one archaeal phylum Euryarchaeota;
      and some accessory microbiota that appear and disappear according to time frame.
      The diet residues and oral microbes, including bacteria, archaea, viruses and
      fungi, consisting of harmless organisms and pathogens associated with local and
      systemic infections have been found trapped in ancient dental calculus by
      morphological approaches, immunolabeling techniques, isotope analyses,
      fluorescent in situ hybridization, DNA-based approaches, and protein-based
      approaches. These observations led to correlation of paleomicrobiology,
      particularly Streptococcus mutans and archaea, with past human health and diet. 

PMID- 26194818
TI  - Increased Oxidative DNA Damage in Placenta Contributes to Cadmium-Induced
      Preeclamptic Conditions in Rat.
AB  - To explore the possible mechanisms of cadmium (Cd)-induced preeclamptic
      conditions in rats. In the present study, we introduced the in vivo model of
      preeclampsia by giving intraperitoneal injections of cadmium chloride (CdCl2) to
      pregnant rats from gestational day (GD) 4 to 19. Maternal body weights were
      recorded on GD 0, 14, and 20, while their systolic blood pressures (SBPs)
      monitored on GD 3, 11, and 18. On GD 20, rats were sacrificed and the specimens
      were collected. The morphological changes of placenta and kidney tissues of
      pregnant rats were examined by hematoxylin and eosin staining assay. Blood Cd
      level was detected by inductively coupled plasma mass spectrometry. Total
      antioxidant capacity (TAC) was evaluated using FRAP method and total nitrite
      (NOx) was detected with Griess reagent. Antioxidative factors and DNA
      damage/repair biomarkers were measured by real-time qPCR, western blot or
      immunohistochemistry study. The current results showed that CdCl2-treated
      pregnant rats developed preeclampsia (PE)-like manifestations, such as
      hypertension, albuminuria, with decreased TAC and increased blood Cd level, and
      pro-oxidative/antioxidative or DNA damage/repair biomarkers. Our study
      demonstrated that increased oxidative DNA damage in placenta could contribute to
      Cd-induced preeclamptic conditions in rat. 

PMID- 26194819
TI  - Elemental Analysis of Asian Elephant (Elephas maximus) Teeth Using X-ray
      Fluorescence and a Comparison to Other Species.
AB  - Elemental composition in bone of the different species has variation depending on
      genetic and environmental factors especially their food habitat. The aims of this
      study were to conduct an elemental analysis of Asian elephant teeth, both
      deciduous (first molar, second molar, and tusk) and permanent (molar and tusk),
      and compare the elemental composition of permanent teeth among 15 species, mostly
      mammalian. These teeth were analyzed using X-ray fluorescence at two voltages: 15
      and 50 kV. In Asian elephants, deciduous tusk showed a lower Ca/Zn ratio compared
      to permanent tusk, because of the lack of Zn in permanent molars. Ca/Fe ratio was
      higher in deciduous than permanent molars. For permanent teeth, elephant molars
      presented a high Ca/Pb ratio but no Ca/Zn, Ca/Sr, and Zn/Fe ratios because of the
      lack of Zn and Sr in the samples tested. The key elemental ratios for
      differentiating elephant deciduous and permanent tusk were Ca/P and Ca/Zn. The
      considerable variation in elemental ratio data across 15 species was observed.
      All tooth samples contained Ca and P, which was not surprising; however, Pb also
      was present in all samples and Cd in a large majority, suggesting exposure to
      environmental contaminants. From discriminant analysis, the combination of
      Ca/P+Ca/Zn+Ca/Pb+Ca/Fe+Ca/Sr+Zn/Fe can generate two equations that successfully
      classified six (dog, pig, goat, tapir, monkey, and elephant) out of 15 species at
      100 % specificity. In conclusion, determining the elemental profile of teeth may
      serve as a tool to identify the tooth "type" of elephants and to potentially
      classify other species. 

PMID- 26194821
TI  - pxn-1 and pxn-2 May Interact Negatively during Neuronal Development and Aging in
      C. elegans.
AB  - C. elegans has two functional peroxidasins (PXN), PXN-1 and PXN-2. PXN-2 is
      essential to consolidate the extracellular matrix during development and is
      suggested to interact with PXN-1 antagonistically. pxn-1 is involved in neuronal
      development and possibly maintenance; therefore, we investigated the relationship
      between pxn-1 and pxn-2 in neuronal development and in aging. During neuronal
      development, defects caused by pxn-1 overexpression were suppressed by
      overexpression of both pxn-1 and pxn-2. In neuronal aging process, pxn-1 mutants
      showed less age-related neuronal defects, such as neuronal outgrowth, neuronal
      wavy processes, and enhanced short-term memory performance. In addition, pxn-2
      overexpressing animals retained an intact neuronal morphology when compared with
      age-matched controls. Consistent with these results, overexpression of both pxn-1
      and pxn-2 restored the severe neuronal defects present with pxn-1 overexpression.
      These results implied that there is a negative relationship between pxn-1 and pxn
      2 via pxn-1 regulating pxn-2. Therefore, pxn-1 may function in neuronal
      development and age-related neuronal maintenance through pxn-2. 

PMID- 26194820
TI  - Exploiting the Fanconi Anemia Pathway for Targeted Anti-Cancer Therapy.
AB  - Genome instability, primarily caused by faulty DNA repair mechanisms, drives
      tumorigenesis. Therapeutic interventions that exploit deregulated DNA repair in
      cancer have made considerable progress by targeting tumor-specific alterations of
      DNA repair factors, which either induces synthetic lethality or augments the
      efficacy of conventional chemotherapy and radiotherapy. The study of Fanconi
      anemia (FA), a rare inherited blood disorder and cancer predisposition syndrome,
      has been instrumental in understanding the extent to which DNA repair defects
      contribute to tumorigenesis. The FA pathway functions to resolve blocked
      replication forks in response to DNA interstrand cross-links (ICLs), and
      accumulating knowledge of its activation by the ubiquitin-mediated signaling
      pathway has provided promising therapeutic opportunities for cancer treatment.
      Here, we discuss recent advances in our understanding of FA pathway regulation
      and its potential application for designing tailored therapeutics that take
      advantage of deregulated DNA ICL repair in cancer. 

PMID- 26194822
TI  - Proteomic Analysis to Identify Tightly-Bound Cell Wall Protein in Rice Calli.
AB  - Rice is a model plant widely used for basic and applied research programs. Plant
      cell wall proteins play key roles in a broad range of biological processes.
      However, presently, knowledge on the rice cell wall proteome is rudimentary in
      nature. In the present study, the tightly-bound cell wall proteome of rice callus
      cultured cells using sequential extraction protocols was developed using mass
      spectrometry and bioinformatics methods, leading to the identification of 1568
      candidate proteins. Based on bioinformatics analyses, 389 classical rice cell
      wall proteins, possessing a signal peptide, and 334 putative non-classical cell
      wall proteins, lacking a signal peptide, were identified. By combining previously
      established rice cell wall protein databases with current data for the classical
      rice cell wall proteins, a comprehensive rice cell wall proteome, comprised of
      496 proteins, was constructed. A comparative analysis of the rice and Arabidopsis
      cell wall proteomes revealed a high level of homology, suggesting a predominant
      conservation between monocot and eudicot cell wall proteins. This study
      importantly increased information on cell wall proteins, which serves for future
      functional analyses of these identified rice cell wall proteins. 

PMID- 26194823
TI  - Dephosphorylation of DBC1 by Protein Phosphatase 4 Is Important for p53-Mediated
      Cellular Functions.
AB  - Deleted in breast cancer-1 (DBC1) contributes to the regulation of cell survival
      and apoptosis. Recent studies demonstrated that DBC is phosphorylated at Thr454
      by ATM/ATR kinases in response to DNA damage, which is a critical event for p53
      activation and apoptosis. However, how DBC1 phosphorylation is regulated has not
      been studied. Here we show that protein phosphatase 4 (PP4) dephosphorylates
      DBC1, regulating its role in DNA damage response. PP4R2, a regulatory subunit of
      PP4, mediates the interaction between DBC1 and PP4C, a catalytic subunit. PP4C
      efficiently dephosphorylates pThr454 on DBC1 in vitro, and the depletion of
      PP4C/PP4R2 in cells alters the kinetics of DBC1 phosphorylation and p53
      activation, and increases apoptosis in response to DNA damage, which are
      compatible with the expression of the phosphomimetic DBC-1 mutant (T454E). These
      suggest that the PP4-mediated dephosphorylation of DBC1 is necessary for
      efficient damage responses in cells. 

PMID- 26194825
TI  - Brazilin from Caesalpinia sappan heartwood and its pharmacological activities: A
      review.
AB  - Caesalpinia sappan L. (CS) is a plant of Leguminosae family, commonly known as
      Brazil or Sappan wood. CS is distributed in Southeast Asia and its dried
      heartwood has been used as traditional ingredient of food or beverages and has a
      wide variety of medicinal properties. Higher extraction yield of CS wood was
      achieved with 95% ethanol for 2 h. Chemical constituent's investigation of sappan
      wood resulted in the isolation of various structural types of phenolic components
      including one xanthone, one coumarin, three chalcones, two flavones three
      homoisoflavonoids and brazilin. Brazilin [(6a S-cis)-7, 11b
      dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10(6H)- tetrol], a major and active
      compound found in CS heartwood. Most of the folkloric uses of brazilin were
      validated by the scientific studies such as antioxidant, antibacterial, anti
      inflammatory, anti-photoaging, hypoglycemic, vasorelaxant, hepatoprotective and
      anti-acne activity. CS heartwood extract is safe and did not produce any acute or
      subacute toxicity in both male and female rats. Brazilin is the safe natural
      compound having potential to develop as a medicinal compound with application in
      food, beverage, cosmetics and pharmaceutical industries to screen its clinical
      use in modern medicine. The information gained could provide the important and
      potential approach for pharmaceutical researcher to implicate the knowledge of
      brazilin in the formulation of new drug and to reveal therapeutic and gaps
      requiring future research opportunities. More studies are needed to evaluate the
      potential application of brazilin as preservative and coloring agent in food
      processing industries. 

PMID- 26194824
TI  - Increased Stability of Nucleolar PinX1 in the Presence of TERT.
AB  - PinX1, a nucleolar protein of 328 amino acids, inhibits telomerase activity,
      which leads to the shortening of telomeres. The C-terminal region of PinX1 is
      responsible for its nucleolar localization and binding with TERT, a catalytic
      component of telomerase. A fraction of TERT localizes to the nucleolus, but the
      role of TERT in the nucleolus is largely unknown. Here, we report a functional
      connection between PinX1 and TERT regarding PinX1 stability. The C-terminal of
      PinX1(205-328), a nucleolar fragment, was much more stable than the N-terminal of
      PinX1(1-204), a nuclear fragment. Interestingly, PinX1 was less stable in TERT
      depleted cells and more stable in TERT-myc expressing cells. Stability assays for
      PinX1 truncation forms showed that both PinX1(1-328) and PinX1(205-328),
      nucleolar forms, were more rapidly degraded in TERT-depleted cells, while they
      were more stably maintained in TERT-overexpressing cells, compared to each of the
      controls. However, PinX1(1-204) was degraded regardless of the TERT status. These
      results reveal that the stability of PinX1 is maintained in nucleolus in the
      presence of TERT and suggest a role of TERT in the regulation of PinX1 steady
      state levels. 

PMID- 26194826
TI  - Antitumor activity of Aponogeton undulatus against Ehrilich ascites carcinoma in
      Swiss albino mice.
AB  - OBJECTIVE: To investigate in vitro antioxidant and in vivo antitumor activity of
      the crude methanolic extract of Aponogeton undulatus (A. undulatus) (MAU) along
      with its various organic fractions. METHODS: A. undulatus leaves were
      successively extracted using methanol (MAU) and then fractionated by chloroform,
      ethyl acetate (EAU) and water. The total antioxidant capacity, lipid peroxidation
      inhibition assay, 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging
      assay and ferrous reducing power assessment were used to evaluate the antioxidant
      potential of the crude extract and its organic fractions. The in vivo antitumor
      activity is evaluated against Ehrlich ascites carcinoma (EAC) cell bearing in
      Swiss albino mice. RESULTS: EAU showed the highest antioxidant capacity as
      (175.80 +/- 0.41) mg/g, IC50 value of DPPH scavenging activity was (38.84 +/-
      0.02) MUg/mL and also exhibited maximum lipid peroxidation inhibition activity
      with the IC50 value of (42.52 +/- 0.32) MUg/mL than other fractions. The results
      demonstrate that reducing power of the extract was concentration dependent. In
      addition, EAU was administered at 50, 100 and 200 mg/kg body weight respectively
      to EAC cell bearing mice and a significant (P < 0.05) decrease in tumor volume,
      packed cell volume and viable cell count and also increased the life span
      (17.52%, 42.53% and 62.05%). Hematological profiles were restored to normal
      levels in MAU treated mice as compared to EAC control mice. CONCLUSIONS: The
      results were found to be significant and confirmed that the A. undulatus has
      remarkable antitumor activity with antioxidant potential.

PMID- 26194827
TI  - High prevalence of multidrug-resistance in Acinetobacter baumannii and
      dissemination of carbapenemase-encoding genes blaOXA-23-like, blaOXA-24-like and
      blaNDM-1 in Algiers hospitals.
AB  - OBJECTIVE: To assess and characterize antibiotic resistance in Acinetobacter
      baumannii strains recovered from 5 health-care facilities in Algiers. METHODS:
      Antibiotic susceptibility testing was performed by agar diffusion and agar
      dilution methods, resistance genes were identified by PCR and sequencing, and
      molecular typing of isolates was carried out by enterobacterial repetitive
      intergenic consensus-PCR (ERIC-PCR). RESULTS: Among 125 tested isolates, 117
      (93.6%) were multidrug-resistant, of which 94 (75.2%) were imipenem resistant.
      The blaADC and blaOXA-51-like genes were detected in all isolates, in association
      with ISAba1 sequence in 84% and 8% (imipenem resistant) of isolates,
      respectively. The blaOXA-23-like and blaOXA-24-like carbapenemase genes were
      detected in 67.02% and 20.21% of imipenem-resistant isolates, respectively. The
      blaOXA-23-like gene is linked to ISAba1 or ISAba4 elements. The metallo-beta
      lactamase NDM-1 gene was found in 10 (10.6%) imipenem-resistant strains from
      three hospitals, it is linked to ISAba125 element in nine strains. Extended
      spectrum beta-lactamases production was not detected. Imipenem and cefotaxime
      resistance phenotypes could not be transferred to Escherichia coli by
      conjugation. Outer membrane protein CarO gene was not detected in four imipenem
      resistant isolates. The aac(6')-Ib, sul1, sul2, tetA and tetB genes were present
      in 5.31%, 36.17%, 77.65%, 1.06% and 65.92% of strains, respectively. Class 1
      integrons were detected in 23.4% strains. ERIC-PCR typing showed a genetic
      diversity among blaOXA-23-like and blaOXA-24-like positive strains, while
      clonality was observed among blaNDM-1 positives. CONCLUSIONS: This study
      highlighted the high prevalence of imipenem resistance in Acinetobacter baumannii
      in Algiers hospitals mediated mainly by blaOXA-23-like, blaOXA-24-like, and
      blaNDM-1 genes.

PMID- 26194828
TI  - Comparison of histopathology and PCR based assay for detection of experimentally
      induced toxoplasmosis in murine model.
AB  - OBJECTIVE: To compare histopathology and PCR based detection in diagnosis of
      experimentally induced toxoplasmosis of RH human strain of the parasite in murine
      models. METHODS: A comparison of histopathology and PCR based detection was done
      to diagnose experimentally induced toxoplasmosis in ten inbred swiss albino mice
      after intraperitoneal inoculation of 100 tachyzoites of laboratory mantained
      human RH strain of the parasite. Tissue samples from lung, liver, spleen, brain,
      heart and kidney were taken and processed for histopathological examination while
      all the samples also were subjected to PCR, using primers directed to the
      multicopy of SAG 3 gene, in dublicates. RESULTS: Histopathology revealed presence
      of tachyzoites only in liver while along with lung, liver, spleen and brain
      tissue yielded desired positive PCR amplicons. CONCLUSIONS: The SAG 3 based PCR
      is able to diagnose toxoplasmosis in those tissues which are declared negative by
      histopathological assay.

PMID- 26194829
TI  - Metabolomics for characterization of gender differences in patients infected with
      dengue virus.
AB  - OBJECTIVE: To determine the metabolic response associate with dengue infection
      based on human gender metabolic differences by means of (1)H NMR-spectrometry.
      METHODS: The mid-stream urine collected from both male and female patients
      diagnosed with dengue fever at Penang General Hospital and fourty-three healthy
      individuals were analyzed with (1)H NMR spectroscopy, followed by chemometric
      multivariate analysis. NMR signals which highlighted in the OPLS-DA S-plot were
      further selected and identified using Human Metabolome Database, Chenomx
      Profiler. RESULTS: The results pointed out that NMR urine profiling was able to
      capture human gender metabolic differences that are important for the distinction
      of classes of individuals of similar physiological conditions; infected with
      dengue. Distinct differences between dengue infected patients versus healthy
      individuals and subtle differences in male versus female infected with dengue
      were found to be related to the metabolism of amino acid and tricarboxylic acid
      intermediates cycle. CONCLUSIONS: The (1)H NMR metabolomic investigation combined
      with appropriate algorithms and pattern recognition procedures, gave an evidence
      for the existence of distinct metabolic differentiation of individuals, according
      to their gender, modulates with the infection risk.

PMID- 26194830
TI  - Schistosoma mansoni infection prevalence and associated risk factors among
      schoolchildren in Demba Girara, Damot Woide District of Wolaita Zone, Southern
      Ethiopia.
AB  - OBJECTIVE: To establish the prevalence and associated risk factors of Schistosoma
      mansoni (S. mansoni) infection among schoolchildren at a village in Wolaita Zone,
      Southern Ethiopia. METHODS: A cross-sectional study was carried out among primary
      schoolchildren. A total of 384 randomly selected study subjects provided stool
      samples for parasitological examination by Kato-Katz and Formalin-Ether
      concentration techniques. Secondary parasitological data were obtained from
      Health Center Laboratory to see the previous history of S. mansoni infection in
      the area. Statistical analysis was performed using SPSS software version 16.
      RESULTS: From the total children examined, 85.4% were found positive for at least
      one helminth infection. S. mansoni infection (81.3%) was the most prevalent and
      the prevalence of STH was 32%. Moderate and heavy infection intensities were only
      observed in S. mansoni infections. The overall heavy intensity of infection was
      56.4%. Contact to Bisare stream was the most important factor for S. mansoni
      infection (OR 3.9) followed by herding cattle near the stream (OR 2.527). Males
      were twice more likely to get the infection than females (OR 1.923). Analysis of
      secondary parasitological data showed that S. mansoni infection was a leading
      helminthic infection over the past years. CONCLUSIONS: The present study found a
      higher intensity and prevalence of S. mansoni infection in a rural village of
      Wolaita Zone. Therefore, appropriate integrated control and prevention measures
      need to be implemented in the study area.

PMID- 26194832
TI  - Effect of mesenchymal stem cells transplantation combining with hyperbaric oxygen
      therapy on rehabilitation of rat spinal cord injury.
AB  - OBJECTIVE: To investigate the effect of BMSCs transplantation plus hyperbaric
      oxygen (HBO) on repair of rat SCI. METHODS: Seventy five male rats were divided
      randomly into five groups: sham, vehicle, BMSCs transplantation group,
      combination group, 15 rats in each group. Every week after the SCI onset, all
      animals were evaluated for behavior outcome by Basso-Beattle-Bresnahan (BBB)
      score and inclined plane test. Axon recovery was examined with focal spinal cord
      tissue by electron microscope at 6 weeks after the SCI onset. HE staining and
      BrdU staining were performed to examine the BMSCs and lesion post injury.
      Somatosensory evoked potential (SEP) testing was performed to detect the recovery
      of neural conduction. RESULTS: Results from the behavior tests from combination
      group were significant higher than rats which received only transplantation or
      HBO treatment. Results from histopathology showed favorable recovery from
      combination group than other treatment groups. The number of BrdU(+) in
      combination group were measureable more than transplantation group (P < 0.05).
      The greatest decrease in TNF-alpha, IL-1beta, IL-6, IFN-alpha determined by Elisa
      assay in combination group were evident too. CONCLUSIONS: BMSCs transplantation
      can promote the functional recovery of rat hind limbs after SCI, and its
      combination with HBO has a synergistic effect.

PMID- 26194831
TI  - Characterization of two Achromobacter xylosoxidans isolates from patients with
      pertussis-like symptoms.
AB  - OBJECTIVE: To characterize two Achromobacter xylosoxidans recovered from 2
      patients diagnosed with pertussis during a Bordetella pertussis surveillance
      program. METHODS: Nasopharyngeal swabs from 2 children under 1 year of age with
      clinical suspicion of pertussis were analyzed by culture and PCR. RESULTS: Two
      Achromobacter xylosoxidans A8, closely related to Bordetella spp. were recovered
      from 2 patients diagnosed of pertussis, both carrying the ptxA gene and IS418 the
      pertussis toxin encoding gene. Subsequently, antibiotic susceptibility was
      evaluated by disk-diffusion method and by PCR. CONCLUSIONS: Although more
      detailed studies are needed, the present data highlight the possibility that
      Achromobacter xylosoxidans, closely related Bordetella pertusssis microorganisms
      and not covered under the vaccine umbrella, might also result in cases of
      whooping cough. Thereby further surveillance is necessary to determine the
      extension and relevance of their pathogenic role in order to discriminate their
      real public health implication.

PMID- 26194833
TI  - Protective effect of TMP on pancreas function of acute pancreatitis rats.
AB  - OBJECTIVE: To explore the protective effect and mechanism of Tetramethy1Pyrazine
      (TMP) on the pancreas function of acute pancreatitis rats. METHODS: A total of 75
      SD rats were randomly divided into three groups (A, B, C) with 25 rats in each
      group. Group A served as sham operation group. In the groups B and C, AP model
      was prepared as by injecting taurocholic acid sodium. Group B was model group.
      After modeling, rats were administrated by intraperitoneal injection of normal
      saline. Group C was TMP treatment group, which was administrated by
      intraperitoneal injection of 0.6% TMP after modeling. The rat blood specimens in
      each group were collected with 1 mL/100 g solution after modeling of 2, 6, 12 and
      24 h. Levels of amylase (AMS), blood urea nitrogen (BUN), creatinine (CR), TNF
      alpha and IL-6 were detected, and 5 rats were sacrificed. Histopathological
      examination was performed in he pancreatic tissue specimens of each group to
      observe pancreatic tissue damage. RESULTS: After modeling in each time point,
      AMS, BUN, CR, TNF-alpha and IL-6 in groups B and C were significantly higher than
      that of in group A (P < 0.05). After modeling of 2 h, AMS, BUN and CR in group B
      increased significantly and reached the peak value at 6 h. After modeling of 12
      h, serum level of TNF-alpha and IL-6 were significantly lower than that of in
      control group, while after 24 h of modeling, serum level of AMS, BUN, CR, TNF
      alpha and IL-6 were significantly lower than that of in control group (P < 0.05).
      The histological observation showed that pancreatic tissue in rats of group A was
      normal without damage lesions. Massive bleeding, necrosis and serious injury were
      visible in pancreatic tissue of group B. The rat pancreatic tissue was bleeding
      in group C with small pieces of necrotic lesions. The degree of inflammatory cell
      infiltration was lower than group B, and the degree of injury was significantly
      lower than group B. CONCLUSIONS: TMP can significantly decrease the serum level
      of TNF-alpha and IL-6 in AP rats, inhibits inflammatory response of AP, and has
      significant protective effect on pancreatic tissue and function in AP rats.

PMID- 26194834
TI  - Mechanism of miR-21 via Wnt/beta-catenin signaling pathway in human A549 lung
      cancer cells and Lewis lung carcinoma in mice.
AB  - OBJECTIVE: To study the mechanism of effect of miR-21 via Wnt/beta-catenin
      signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in
      mice. METHODS: The effect of miR-21 on A549 cells were detected by MTT method.
      MiR-21 expression levels were overexpressed or inhibited in A549 cells by
      transfecting with miR-21 mimics or inhibitors. Correlation among key molecules
      (Wnt1, beta-catenin, CyclinD1 and miR-21) of mRNA and protein levels in Wnt/beta
      catenin signaling pathway were studied by Real-time PCR and Western blot
      hybridization assay. Invasive ability of A549 cells was determined via Transwell
      chamber cell invasion assay; the role of miR-21 in A549 cells was explored via
      the Wnt/beta-catenin signaling pathway. A Lewis lung carcinoma animal model was
      established to detect miR-21 expressions in tumor animals and controlled animal
      tissues, and verify expression changes of the above molecules in the Wnt/beta
      catenin signaling pathway was determined in the animal level. RESULTS: MTT assay
      results showed that miR-21 overexpression could markedly enhance cell absorbance
      value; that is, miR-21 could increase the ability proliferation of A549 cells.
      beta-catenin and CyclinD1 expression levels were significantly higher in miR-21
      mimic transfected cells (P < 0.05), and Wnt1 gene had no significant change.
      Wnt1, beta-catenin and CyclinD1 gene expression showed no significant change when
      miR-21 expression was suppressed, compared with controls. After cells were
      transfected with miR-21 mimics, cell invasion assay revealed that the perforated
      cells was significantly higher than the perforated cells in the control group (P
      < 0.01). Lewis lung assay revealed that miR-21 expression levels in the Lewis
      lung carcinoma were significantly higher; and at the same time, Wnt1, beta
      catenin and CyclinD1 gene expression levels were significantly increased,
      compared to controls. CONCLUSIONS: In A549 human lung cancer cells and Lewis lung
      carcinoma in mice, key molecules beta-catenin and CyclinD1of miR-21 expressions
      and the Wnt/beta-catenin signaling pathway are positively correlated.

PMID- 26194835
TI  - Effect of bortezomib on migration and invasion in cervical carcinoma HeLa cell.
AB  - OBJECTIVE: To explore the effect of bortezomib on migration and invasion of
      cervical carcinoma HeLa cell and specific molecular mechanism. METHODS: The
      effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The
      effect of bortezomib on cell migration and invasion was measured by Transwell
      assay and invasion experiment respectively. The activation of Akt/mTOR signaling
      pathway and expression level of MMP2, MMP9 were assayed by western blot. RESULTS:
      MTT assay indicated bortezomib (2.5 MUM, 5 MUM, 10 MUM) could inhibit HeLa cell
      viability, and the inhibitory rate was highest at 48 h. Transwell assay and
      invasion experiment results showed that bortezomib inhibited HeLa cell migration
      and invasion. Western blotting assays presented bortezomib could suppress the
      phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and
      MMP9. CONCLUSIONS: These results suggested bortezomib could inhibit migration and
      invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR
      signal pathway.

PMID- 26194836
TI  - Netrin-1: The new tumor markers in renal clear cell carcinoma.
AB  - OBJECTIVE: To explore the expression of Netrin-1 protein in human renal clear
      cell carcinoma (RCCC) and the relationships between Netrin-1, pathology and
      prognosis. METHODS: 72 cases of RCCC admitted in our hospital from 2008 June to
      2009 June and their adjacent tissues were selected for study. They included 30
      cases in stage I-II, 42 cases in stage III-IV; 9 cases in grade I, 9 cases in
      grade II, 40 cases in grade III and 14 cases in grade IV. All cases were followed
      up for more than 5 years. Survival analysis lines were made by Kaplan-Meier
      method and the difference between groups was tested by the Log-rank test. The
      expression of Netrin-1 protein was detected by immunohistochemistry staining and
      its clinical significance was analyzed. RESULTS: Renal clear cell carcinoma: 51
      cases in high expression of Netrin-1 and 21 cases in low expression, normal
      tissues: 12 cases in high expression of Netrin-1 and 60 cases in low expression,
      the difference between the two groups is significant (chi(2) = 42.921, P < 0.01).
      The difference of the expression of Netrin-1in Fuhrman grade and AJCC clinical
      stage is significant (chi(2) = 8.000, chi(2) = 6.203; P<0.05). The 5-year
      survival rate in low protein expression group and in high protein expression
      group was 79% (17/21) and 62% (32/51). The survival curve had different trend,
      with no significant difference between groups ((chi(2) = 1.360, P = 0.245).
      CONCLUSIONS: Netrin-1 protein plays an important role in the development of RCCC.
      It might be a new specific tumor marker of RCCC, and might become a new target in
      treatment of RCCC.

PMID- 26194837
TI  - Effect of 1,25-dihydroxyvitamin D3 on mast cells tryptase in asthmatic guinea
      pigs.
AB  - OBJECTIVE: To explore the effect of 1,25-dihydroxyvitamin D3 on the mast cell
      tryptase (MCT) in asthmatic guinea pigs. METHODS: A total of 60 male or female
      healthy guinea pigs were randomly divided into control group (group A), asthmatic
      group (group B), and 1,25-dihydroxyvitamin D3 group (group C), with 20 cases in
      each group. To establish asthmatic guinea pig models, 1 mL peanut oil was filled
      into stomach in the morning in group A and group B, and 1 mL peanut oil with 1,25
      dihydroxyvitamin D3 was filled into stomach in group C. Airway resistance (Re) of
      asthmatic guinea pigs was detected, and the bronchoalveolar lavage fluid (BALF)
      cells were counted. Lung tissue with HE and MCT immunohistochemical staining were
      used to observe the pathological changes in lung tissue and the distribution of
      MCT. RESULTS: After injection of different concentration of acetylcholine
      chloride, the Re in group B and group C were increased significantly compared
      with group A (P < 0.05); compared with group B, the Re in group C were decreased
      significantly (t = -5.385, -5.761, -6.184, -13.574, P < 0.05); the total number
      of BALF cells and eosinophils were increased significantly in group B and C (t =
      19.618, 9.598, 10.854, 5.388, P < 0.05); compared with group B, the total number
      of BALF cells and eosinophils in group C was decreased significantly (t = -5.555,
      -5.392, P < 0.05); the number of tryptase positive cells in group B was increased
      significantly than that in group A (t = 21.312, P < 0.05), and in addition to the
      alveolar septum and submucosa, the cells were also distributed around blood
      vessels and outside the cells; the number of tryptase positive cells in group C
      was decreased significantly compared with group B, and the difference was
      statistically significant (t = 5.043, P < 0.05). CONCLUSIONS: After the asthmatic
      guinea pigs are treated with 1,25-dihydroxyvitamin D3, their BALF, Re,
      infiltration degree of inflammatory cells in the trachea and lung tissue and
      airway inflammatory reaction are reduced significantly. 1,25-dihydroxyvitamin D3
      has a certain inhibiting effect on the activation of mast cells and the release
      of MCT granules.

PMID- 26194838
TI  - Protective effect of telmisartan on rats with renal failure and its mechanism.
AB  - OBJECTIVE: To study the protective effect of telmisartan on rats with renal
      failure and its mechanism. METHODS: 60 Wistar rats were chosen as study
      objective, and were divided into 4 groups randomly: 15 in group A (sham operation
      group), 15 in group B (model group), 15 in group C (telmisartan group) and 15 in
      group D (telmisartan + GW9962 group). The difference of survival rate, blood
      urine biochemical indexes, renal pathological change, and the expression level of
      PPARgamma and nNOS were compared. RESULTS: After 12 weeks, the survival rate of
      group A was 93.33% (14/15), that of group B was 46.67% (7/15), that of group C
      was 86.67% (13/15), that of group D was 60.00% (9/15), and the difference among 4
      groups had statistical significance (P < 0.05). After 1 week, the difference of
      Scr, that of BUN and that of 24 h protein urine among 4 groups was not
      statistical significant (P > 0.05); after 3 weeks, 6 weeks and 12 weeks, these
      difference was statistical significant (P < 0.05). The difference of blood-urine
      biochemical indexes, that of renal pathological change, and that of the
      expression level of PPARgamma and nNOS was statistical significant (P < 0.05).
      CONCLUSIONS: Telmisartan has protective effect on renal failure caused by 5/6
      nephrectomy, which might be relative to the expression level of PPARgamma and
      nNOS.

PMID- 26194839
TI  - Effect of microRNA-101 on apoptosis of rabbit condylar cartilage cells by
      inhibiting target gene SOX9.
AB  - OBJECTIVE: To explore the effect of microRNA-101 on apoptosis of condylar
      cartilage cells and the specific mechanism of molecular biology. METHODS: IL-1
      was used to stimulate and establish the model of apoptosis of condylar cartilage
      cells. The expression change of miR-101 in control group was compared with that
      in IL-1 stimulation group by qRT-PCR. Overexpression and down-regulation models
      of miR-101 were established by transfecting Mimics and Inhibitor and verified by
      qRT-PCR. Flow cytometry was used to detect the effect of miR-101 overexpression
      and down-regulation on apoptosis. Target gene of miR-101 was analyzed and
      calculated through bioinformatics. Western blot and Luciferase report assay were
      used to detect whether SOX9 could become the target gene of miR-101. RESULTS: qRT
      PCR results showed that IL-1 stimulation could cause the increase of miR-101
      expression. After the transfection of rabbit condylar cartilage cells by Mimics
      and Inhibitor, qRT-PCR results confirmed the significant effect of miR-101
      overexpression and down-regulation. It was confirmed by flow cytometry that
      overexpression of miR-101 could promote the apoptosis of condylar cartilage
      cells, and down-regulation of miR-101 could reduce the apoptosis. It was
      confirmed by Western blot and Luciferase report assay that SOX9 was the target
      gene of miR-101, and miR-101 inhibited SOX9 expression through complementary
      pairing with 3'UTR of SOX9 mRNA. CONCLUSIONS: miR-101 can promote the apoptosis
      of condylar cartilage cells through inhibiting the protein level of target gene
      SOX9.

PMID- 26194840
TI  - Abstracts of Scientific Papers Presented at the 18th Annual Meeting of the
      Biofeedback Federation of Europe.

PMID- 26194841
TI  - Determination and Pharmacokinetic Study of Apatinib in Rat Plasma by UPLC.
AB  - In this study, a simple, sensitive, and robust analytical method based on ultra
      performance liquid chromatography (UPLC) has been developed for the determination
      of apatinib in rat plasma using carbamazepine as internal standard (IS). After
      sample preparation by a simple liquid-liquid extraction, chromatography was
      performed on an Acquity UPLC BEH C18 column (2.1 * 50 mm, 1.7 um particle size)
      and total run time was 2.0 min. The method was linear over the concentration
      range 5-1000 ng/mL with a lower limit of quantification of 5 ng/mL. Inter- and
      intraday precision were all within 6.5% and the accuracy was <=3.5%. Recoveries
      of apatinib and IS were >80%. Stability studies showed that apatinib was stable
      under a variety of storage conditions. The method was successfully applied to a
      pharmacokinetic study involving oral administration of apatinib to rats. 

PMID- 26194842
TI  - A simple HPLC-UV method for the quantification of theophylline in rabbit plasma
      and its pharmacokinetic application.
AB  - A simple, precise and accurate high-performance liquid chromatography-ultraviolet
      method was developed and validated for the quantification of theophylline in
      rabbit plasma using hydroxyethyl theophylline as an internal standard. Separation
      was performed on Waters((r)) C18 column (uBondapakTM 5 um, 150 * 3.9 mm) using a
      mobile phase consisting of water-acetonitrile (96:4 v/v) at a flow rate of 1
      mL/min. Validation of the method was performed in order to demonstrate its
      selectivity, linearity, precision, accuracy and stability. The calibration curves
      of theophylline were linear over a concentration range of 0.1-25 ug/mL. The
      within- and between-day coefficient of variation (CV) were <10%. The extraction
      recoveries of theophylline at the three levels of quality control samples were
      63.1, 69.4 and 69.7%. The method was rapid with retention time of theophylline
      and the internal standard observed at ~5.2 and 6.5 min, respectively. The
      developed method was applied successfully for studying the pharmacokinetics of
      theophylline in rabbits. 

PMID- 26194844
TI  - Sleep Quality and Reexperiencing Symptoms of PTSD Are Associated With Current
      Pain in U.S. OEF/OIF/OND Veterans With and Without mTBIs.
AB  - Pain, a debilitating condition, is frequently reported by U.S. veterans returning
      from Afghanistan and Iraq. This study investigated how commonly reported clinical
      factors were associated with pain and whether these associations differed for
      individuals with a history of chronic pain. From the Boston metropolitan area,
      171 veterans enrolled in the Veterans Affairs Center of Excellence were assessed
      for current posttraumatic stress disorder (PTSD) symptom severity, current mood
      and anxiety diagnoses, lifetime traumatic brain injury, combat experiences, sleep
      quality, and alcohol use. Hierarchical regression models were used to determine
      the association of these conditions with current pain. Average pain for the
      previous 30 days, assessed with the McGill Pain Questionnaire, was 30.07 out of
      100 (SD = 25.43). Sleep quality, PTSD symptom severity, and alcohol use were
      significantly associated with pain (R(2) = .24), as were reexperiencing symptoms
      of PTSD (R(2) = .25). For participants with a history of chronic pain (n = 65),
      only PTSD symptoms were associated with pain (R(2) = .19). Current pain severity
      was associated with increased PTSD severity (notably, reexperiencing symptoms),
      poor sleep quality, and increased alcohol use. These data support the hypothesis
      that PTSD symptoms influence pain, but suggest that problems with sleep and
      alcohol use may exacerbate the relationship.

PMID- 26194845
TI  - [Training of residents in obstetrics and gynecology: Assessment of an educational
      program including formal lectures and practical sessions using simulators].
AB  - OBJECTIVES: Evaluate an educational program in the training of residents in
      gynecology-obstetrics (GO) with a theory session and a practical session on
      simulators and analyze their learning curve. METHODS: Single-center prospective
      study, at the university hospital (CHU). Two-day sessions were leaded in April
      and July 2013. An evaluation on obstetric and gynecological surgery simulator was
      available to all residents. Theoretical knowledge principles of obstetrics were
      evaluated early in the session and after formal lectures was taught to them. At
      the end of the first session, a satisfaction questionnaire was distributed to all
      participants. RESULTS: Twenty residents agreed to participate to the training
      sessions. Evaluation of theoretical knowledge: at the end of the session, the
      residents obtained a significant improvement in their score on 20 testing
      knowledge. Obstetrical simulator: a statistically significant improvement in
      scores on assessments simulator vaginal delivery between the first and second
      session. Subjectively, a larger increase feeling was seen after breech delivery
      simulation than for the cephalic vaginal delivery. However, the confidence level
      of the resident after breech delivery simulation has not been improved at the end
      of the second session. Simulation in gynecological surgery: a trend towards
      improvement in the time realized on the peg-transfer between the two sessions was
      noted. In the virtual simulation, no statistically significant differences
      showed, no improvement for in salpingectomy's time. Subjectively, the residents
      felt an increase in the precision of their gesture. Satisfaction: All residents
      have tried the whole program. They considered the pursuit of these sessions on
      simulators was necessary and even mandatory. CONCLUSION: The approach chosen by
      this structured educational program allowed a progression for the residents, both
      objectively and subjectively. This simulation program type for the resident's
      training would use this tool in assessing their skills and develop learning
      curves.

PMID- 26194846
TI  - The pain receptor TRPV1 displays agonist-dependent activation stoichiometry.
AB  - The receptor channel TRPV1 (Transient Receptor Potential Vanilloid 1) is
      expressed by primary afferent sensory neurons of the pain pathway, where it
      functions as a sensor of noxious heat and various chemicals, including
      eicosanoids, capsaicin, protons and peptide toxins. Comprised of four identical
      subunits that organize into a non-selective cationic permeable channel, this
      receptor has a variety of binding sites responsible for detecting their
      respective agonists. Although its physiological role as a chemosensor has been
      described in detail, the stoichiometry of TRPV1 activation by its different
      ligands remains unknown. Here, we combined the use of concatemeric constructs
      harboring mutated binding sites with patch-clamp recordings in order to determine
      the stoichiometry for TRPV1 activation through the vanilloid binding site and the
      outer-pore domain by capsaicin and protons, respectively. We show that, while a
      single capsaicin-bound subunit was sufficient to achieve a maximal open-channel
      lifetime, all four proton-binding sites were required. Thus, our results
      demonstrate a distinct stoichiometry of TRPV1 activation through two of its
      different agonist-binding domains. 

PMID- 26194847
TI  - A Case of Complete Recovery of Fluctuating Monocular Blindness Following
      Endovascular Treatment in Internal Carotid Artery Dissection.
AB  - BACKGROUND: Monocular blindness may appear as the first symptom of internal
      carotid artery dissection (ICAD). However, there have been no reports that
      monocular visual loss repeatedly occurs and disappears in response to postural
      change in ICAD. METHODS: A 33-year-old woman presented with transient monocular
      blindness (TMB) following acute-onset headache. TMB repeatedly occurred in
      response to postural change. Two days later, she experienced transient dysarthria
      and right hemiparesis in upright position. Pupil size and light reflex were
      normal, but a relative afferent pupillary defect was positive in the left eye.
      Diffusion-weighted imaging showed no acute lesion, but perfusion-weighted imaging
      showed perfusion delay in the left ICA territory. Digital subtraction angiography
      demonstrated a false lumen and an intraluminal filling defect in proximal segment
      of the left ICA. RESULTS: Carotid stenting was performed urgently. After carotid
      stenting, left relative afferent pupillary defect disappeared and TMB was not
      provoked anymore by upright posture. At discharge, left visual acuity was
      completely normalized. CONCLUSIONS: Because fluctuating visual symptoms in the
      ICAD may be associated with hemodynamically unstable status, assessment of the
      perfusion status should be done quickly. Carotid stenting may be helpful to
      improve the fluctuating visual symptoms and hemodynamically unstable status in
      selected patient with the ICAD.

PMID- 26194848
TI  - Cerebral Blood Flow after Acute Bypass with Parent Artery Trapping in Patients
      with Ruptured Supraclinoid Internal Carotid Artery Aneurysms.
AB  - BACKGROUND: Bypass with parent artery trapping is an alternative treatment method
      for ruptured internal carotid artery (ICA) aneurysms when clipping or coiling is
      contraindicated. However, the efficacy and safety of this strategy during the
      acute stage of subarachnoid hemorrhage (SAH) is undetermined. METHODS: A
      retrospective review of 955 consecutive patients presenting SAH between 2006 and
      2014 identified 17 patients with ruptured ICA aneurysms treated by bypass with
      parent artery trapping within 72 hours after the bleeding (bypass group). The 26
      cases with ruptured posterior communicating artery aneurysms treated with
      clipping during the same period were defined as a control group (clipping group).
      Postoperative cerebral blood flow (CBF) was evaluated by single photon emission
      computed tomography (SPECT). We analyzed the postoperative hemodynamic status,
      surgical complications, and the clinical outcomes. RESULTS: Postoperative
      rebleeding did not occur in any of the cases. CBF in the first postoperative week
      in the bypass group was lower than that in the clipping group (P = .0165). This
      CBF decrease improved in the second postoperative week and did not differ from
      that of the clipping group. The incidence of acute ischemic complications was
      significantly higher in the bypass group (P = .0284), but the incidence of
      delayed cerebral ischemia did not differ between the 2 groups. The incidence of
      favorable outcomes at 6 months was 82.4% in the bypass group and 81% in the
      clipping group. CONCLUSIONS: Although the transient CBF decrease with acute
      ischemic complications should be noted, acute bypass with parent artery trapping
      is safe and effective for unclippable/uncoilable ruptured ICA aneurysms.

PMID- 26194849
TI  - Sarcopenia, as defined by low muscle mass, strength and physical performance,
      predicts complications after surgery for colorectal cancer.
AB  - AIM: Recent studies have shown that sarcopenia is associated with negative
      postoperative outcomes. However, none of these studies analysed muscle strength
      or physical performance, which are also important components of sarcopenia. The
      present study aimed to investigate whether sarcopenia itself, as defined by low
      muscle mass, strength and physical performance, would predict complications after
      surgery for colorectal cancer. METHOD: We conducted a prospective study of
      patients who underwent surgery for colorectal cancer at our department between
      August 2014 and February 2015. Sarcopenia was diagnosed by a combination of third
      lumbar vertebra muscle index (L3 MI), handgrip strength and 6-m usual gait speed.
      Univariate and multivariate analyses evaluating the risk factors for
      postoperative complications were performed. Only complications classified as
      Grade II or above according to the Clavien-Dindo classification were analysed in
      this study. RESULTS: A total of 142 patients were included in the study, and 17
      patients were diagnosed as having sarcopenia. Postoperative complications of
      Grade II or above occurred in 40 patients, including 10 with sarcopenia and 30
      without sarcopenia. Multivariate analysis showed that sarcopenia and previous
      abdominal surgery were independent risk factors for postoperative complications.
      Patients with sarcopenia also had an obvious tendency to a higher incidence of
      infectious complications. By comparing two logistic regression models, sarcopenia
      showed a better predictive power for postoperative complications than did low
      muscle mass. CONCLUSION: Sarcopenia and previous abdominal surgery are
      independent risk factors for complications after surgery for colorectal cancer.
      Including a functional aspect to the definition of sarcopenia may result in a
      better prediction of postoperative complications.

PMID- 26194850
TI  - Nutrient supplementation may adversely affect maternal oral health--a randomised
      controlled trial in rural Malawi.
AB  - Nutritional supplementation during pregnancy is increasingly recommended
      especially in low-resource settings, but its oral health impacts have not been
      studied. Our aim was to examine whether supplementation with multiple
      micronutrients (MMN) or small-quantity lipid-based nutrient supplements affects
      dental caries development or periodontal health in a rural Malawian population.
      The study was embedded in a controlled iLiNS-DYAD trial that enrolled 1391
      pregnant women <20 gestation weeks. Women were provided with one daily iron-folic
      acid capsule (IFA), one capsule with 18 micronutrients (MMN) or one sachet of
      lipid-based nutrient supplements (LNS) containing protein, carbohydrates,
      essential fatty acids and 21 micronutrients. Oral examination of 1024
      participants was conducted and panoramic X-ray taken within 6 weeks after
      delivery. The supplement groups were similar at baseline in average socio
      economic, nutritional and health status. At the end of the intervention, the
      prevalence of caries was 56.7%, 69.1% and 63.3% (P = 0.004), and periodontitis
      34.9%, 29.8% and 31.2% (P = 0.338) in the IFA, MMN and LNS groups, respectively.
      Compared with the IFA group, women in the MMN group had 0.60 (0.18-1.02) and in
      the LNS group 0.59 (0.17-1.01) higher mean number of caries lesions. In the
      absence of baseline oral health data, firm conclusions on causality cannot be
      drawn. However, although not confirmatory, the findings are consistent with a
      possibility that provision of MMN or LNS may have increased the caries incidence
      in this target population. Because of the potential public health impacts,
      further research on the association between gestational nutrient interventions
      and oral health in low-income settings is needed.

PMID- 26194851
TI  - Modeling ligand recognition at the P2Y12 receptor in light of X-ray structural
      information.
AB  - The G protein-coupled P2Y12 receptor (P2Y12R) is an important antithrombotic
      target and of great interest for pharmaceutical discovery. Its recently solved,
      highly divergent crystallographic structures in complex either with nucleotides
      (full or partial agonist) or with a nonnucleotide antagonist raise the question
      of which structure is more useful to understand ligand recognition. Therefore, we
      performed extensive molecular modeling studies based on these structures and
      mutagenesis, to predict the binding modes of major classes of P2Y12R ligands
      previously reported. Various nucleotide derivatives docked readily to the agonist
      bound P2Y12R, but uncharged nucleotide-like antagonist ticagrelor required a
      hybrid receptor resembling the agonist-bound P2Y12R except for the top portion of
      TM6. Supervised molecular dynamics (SuMD) of ticagrelor binding indicated
      interactions with the extracellular regions of P2Y12R, defining possible meta
      binding sites. Ureas, sulfonylureas, sulfonamides, anthraquinones and glutamic
      acid piperazines docked readily to the antagonist-bound P2Y12R. Docking
      dinucleotides at both agonist- and antagonist-bound structures suggested
      interactions with two P2Y12R pockets. Thus, our structure-based approach
      consistently rationalized the main structure-activity relationships within each
      ligand class, giving useful information for designing improved ligands. 

PMID- 26194852
TI  - Vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitors: development
      and validation of predictive 3-D QSAR models through extensive ligand- and
      structure-based approaches.
AB  - Vascular endothelial growth factor receptor-2, (VEGFR-2), is a key element in
      angiogenesis, the process by which new blood vessels are formed, and is thus an
      important pharmaceutical target. Here, 3-D quantitative structure-activity
      relationship (3-D QSAR) were used to build a quantitative screening and
      pharmacophore model of the VEGFR-2 receptors for design of inhibitors with
      improved activities. Most of available experimental data information has been
      used as training set to derive optimized and fully cross-validated eight mono
      probe and a multi-probe quantitative models. Notable is the use of 262 molecules,
      aligned following both structure-based and ligand-based protocols, as external
      test set confirming the 3-D QSAR models' predictive capability and their
      usefulness in design new VEGFR-2 inhibitors. From a survey on literature, this is
      the first generation of a wide-ranging computational medicinal chemistry
      application on VEGFR2 inhibitors. 

PMID- 26194853
TI  - The origin of Cretaceous black shales: a change in the surface ocean ecosystem
      and its triggers.
AB  - Black shale is dark-colored, organic-rich sediment, and there have been many
      episodes of black shale deposition over the history of the Earth. Black shales
      are source rocks for petroleum and natural gas, and thus are both geologically
      and economically important. Here, we review our recent progress in understanding
      of the surface ocean ecosystem during periods of carbonaceous sediment
      deposition, and the factors triggering black shale deposition. The stable
      nitrogen isotopic composition of geoporphyrins (geological derivatives of
      chlorophylls) strongly suggests that N2-fixation was a major process for
      nourishing the photoautotrophs. A symbiotic association between diatoms and
      cyanobacteria may have been a major primary producer during episodes of black
      shale deposition. The timing of black shale formation in the Cretaceous is
      strongly correlated with the emplacement of large igneous provinces such as the
      Ontong Java Plateau, suggesting that black shale deposition was ultimately
      induced by massive volcanic events. However, the process that connects these
      events remains to be solved.

PMID- 26194854
TI  - Discovery of NKT cells and development of NKT cell-targeted anti-tumor
      immunotherapy.
AB  - Natural Killer T (NKT) cells are unique lymphocytes characterized by their
      expression of a single invariant antigen receptor encoded by Valpha14Jalpha18 in
      mice and Valpha24Jalpha18 in humans, which recognizes glycolipid antigens in
      association with the monomorphic CD1d molecule. NKT cells mediate adjuvant
      activity to activate both CD8T cells to kill MHC-positive tumor cells and NK
      cells to eliminate MHC-negative tumor at the same time in patients, resulting in
      the complete eradication of tumors without relapse. Therefore, the NKT cell
      targeted therapy can be applied to any type of tumor and also to anyone
      individual, regardless of HLA type.Phase IIa clinical trials on advanced lung
      cancers and head and neck tumors have been completed and showed significantly
      prolonged median survival times with only the primary treatment. Another
      potential treatment option for the future is to use induced pluripotent stem cell
      (iPS)-derived NKT cells, which induced adjuvant effects on anti-tumor responses,
      inhibiting in vivo tumor growth in a mouse model.

PMID- 26194855
TI  - Strength and precision of neurotransmission at mammalian presynaptic terminals.
AB  - Classically, the basic concept of chemical synaptic transmission was established
      at the frog neuromuscular junction, and direct intracellular recordings from
      presynaptic terminals at the squid giant presynaptic terminal have further
      clarified principles of neurotransmitter release. More recently, whole-cell patch
      camp recordings from the calyx of Held in rodent brainstem slices have extended
      the classical concept to mammalian synapses providing new insights into the
      mechanisms underlying strength and precision of neurotransmission and
      developmental changes therein. This review summarizes findings from our
      laboratory and others on these subjects, mainly at the calyx of Held, with a
      particular focus on precise, high-fidelity, fast neurotransmission. The
      mechanisms by which presynaptic terminals acquire strong, precise
      neurotransmission during postnatal development are also discussed.

PMID- 26194857
TI  - Acknowledging the Limitations of Treatment: Surrendering to Reality.

PMID- 26194856
TI  - Mechanism of the calcium-regulation of muscle contraction--in pursuit of its
      structural basis.
AB  - The author reviewed the research that led to establish the structural basis for
      the mechanism of the calcium-regulation of the contraction of striated muscles.
      The target of calcium ions is troponin on the thin filaments, of which the main
      component is the double-stranded helix of actin. A model of thin filament was
      generated by adding tropomyosin and troponin. During the process to provide the
      structural evidence for the model, the troponin arm was found to protrude from
      the calcium-depleted troponin and binds to the carboxyl-terminal region of actin.
      As a result, the carboxyl-terminal region of tropomyosin shifts and covers the
      myosin-binding sites of actin to block the binding of myosin. At higher calcium
      concentrations, the troponin arm changes its partner from actin to the main body
      of calcium-loaded troponin. Then, tropomyosin shifts back to the position near
      the grooves of actin double helix, and the myosin-binding sites of actin becomes
      available to myosin resulting in force generation through actin-myosin
      interactions.

PMID- 26194859
TI  - Presentations to Alberta emergency departments for asthma: a time series
      analysis.
AB  - OBJECTIVES: Asthma is a common chronic respiratory condition, and exacerbations
      may cause individuals to seek care in emergency departments (EDs). This study
      examines the monthly patterns of asthma presentations to EDs in Alberta, Canada.
      METHODS: All presentations to the ED for asthma from April 1999 to March 2011
      were extracted from provincial administrative health databases. Data included
      age, sex, and health zone of residence. Crude rates per 100,000 population were
      calculated. Seasonal autoregressive integrated moving average (SARIMA) time
      series models were developed. RESULTS: There were a total of 362,430 ED
      presentations for asthma, and the monthly rate of presentation declined from
      115.5 to 41.6 per 100,000 during the study period. Males made 50.1% of ED
      presentations, and adults made 52.8%. The absolute number of ED presentations for
      asthma declined in each of the five administrative health zones in the province,
      with smaller percentage decreases seen in the most urbanized zones (32.1%) than
      the other zones (46.9%). One SARIMA model closely predicted overall presentation
      rates as well as the rates of ED presentations for age and zone subgroups. These
      models showed strong seasonal components, with the strongest estimates occurring
      for the pediatric subgroup and the southernmost provincial zone. CONCLUSIONS:
      Rates of ED presentations for asthma have been declining in this province during
      the past decade. The reasons for this decline warrant further exploration. The
      SARIMA models quantified the temporal patterns and may be helpful for planning
      research and health care service needs.

PMID- 26194858
TI  - Molecular Testing in Myelodysplastic Syndromes for the Practicing Oncologist:
      Will the Progress Fulfill the Promise?
AB  - Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic neoplasms that
      are driven by somatically acquired genetic mutations and epigenetic alterations.
      Accurate risk stratification is essential for delivery of risk-adaptive
      therapeutic interventions. The current prognostic tools sum the impact of
      clinical, pathologic, and laboratory parameters. Newer technologies with next
      generation targeted deep sequencing and whole-genome and -exome sequencing have
      identified several recurrent mutations that play a vital role in the
      pathophysiology of MDS and the impact of these genetic changes on disease
      phenotype. Equally important, well-annotated databases of MDS patients with
      paired clinicopathologic and genetic data have enabled better understanding of
      the independent prognostic impact of several molecular mutations on important
      clinical endpoints such as overall survival and probability of leukemic
      progression. Cumulative evidence suggests that genomic data can also be used
      clinically to aid with the diagnosis, prognosis, prediction of response to
      specific therapies, and the development of novel and rationally targeted
      therapies. However, the optimal use of this mutational profiling remains a work
      in progress and currently there is no standard set of genes or techniques that
      are recommended for routine use in the clinic. In this review, we discuss the
      genomic revolution and its impact on our understanding of MDS biology and risk
      stratification. We also discuss the current role and the challenges of the
      application of genetic mutational data into daily clinical practice and how
      future research could help improve the prognostication precision and specific
      therapy selection for patients with MDS. IMPLICATIONS FOR PRACTICE: Heterogeneity
      in clinical outcomes of MDS is partly related to interpatient variability of
      recurrent somatic mutations that drive disease phenotype and progression.
      Although clinical risk stratification tools have functioned well in
      prognostication for patients with MDS, their ability to predict clinical benefits
      of specific MDS therapies is limited. Molecular testing shows promise in aiding
      diagnosis, risk stratification, and therapy-specific benefit prediction for MDS
      patients. Nonetheless, logistical issues related to assay performance
      standardization, validation, interpretation, and development of guidelines for
      how to use the results to inform clinical decisions are yet to be resolved.

PMID- 26194860
TI  - Postoperative CT in pancreas transplantation.
AB  - AIM: To examine the usage and value of computed tomography (CT) following
      simultaneous pancreas and kidney (SPK) transplantation. MATERIALS AND METHODS:
      Indications for postoperative CT, key findings, and their influence on management
      were determined by retrospective analysis. RESULTS: Ninety-eight patients
      underwent 313 CT examinations. Common indications for the examinations included
      suspected intra-abdominal collection (31.1%) and elevated serum amylase/lipase
      (24.1%). CT findings most frequently showed non-specific mild inflammation
      (27.6%), a normal scan (17.1%) and fluid collections (16.3%). High capillary
      blood glucose (CBG) was associated with resultant CT demonstration of graft
      vascular abnormalities, but otherwise, particular clinical indications were not
      associated with specific CT findings. CONCLUSION: Clinical findings in patients
      with SPK transplants are non-specific. The pattern of abnormalities encountered
      is significantly different to those seen in native pancreatic disease and demands
      a tailored protocol. CT enables accurate depiction of vascular abnormalities and
      fluid collections, thus reducing the number of surgical interventions that might
      otherwise be required. Elevated CBG should prompt urgent CT to exclude
      potentially reversible vascular complications.

PMID- 26194861
TI  - Fitting additive hazards models for case-cohort studies: a multiple imputation
      approach.
AB  - In this paper, we consider fitting semiparametric additive hazards models for
      case-cohort studies using a multiple imputation approach. In a case-cohort study,
      main exposure variables are measured only on some selected subjects, but other
      covariates are often available for the whole cohort. We consider this as a
      special case of a missing covariate by design. We propose to employ a popular
      incomplete data method, multiple imputation, for estimation of the regression
      parameters in additive hazards models. For imputation models, an imputation
      modeling procedure based on a rejection sampling is developed. A simple
      imputation modeling that can naturally be applied to a general missing-at-random
      situation is also considered and compared with the rejection sampling method via
      extensive simulation studies. In addition, a misspecification aspect in
      imputation modeling is investigated. The proposed procedures are illustrated
      using a cancer data example. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26194862
TI  - Migration-induced variation of fatty acid transporters and cellular metabolic
      intensity in passerine birds.
AB  - Because lipids are the main fuel supporting avian endurance activity, lipid
      transport and oxidation capacities may increase during migration. We measured
      enzyme activities, mRNA expression and protein levels in pectoralis and heart for
      several key steps of lipid transport and catabolism pathways to investigate
      whether these pathways were upregulated during migration. We used yellow-rumped
      (Setophaga coronata) and yellow (S. petechia) warblers and warbling vireos (Vireo
      gilvus) as study species because they all show migration-induced increases in
      organismal metabolic capacities. For yellow-rumped warblers, beta-hydroxyacyl CoA
      dehydrogenase (HOAD) activities and fatty acid transporter mRNA and/or protein
      levels were higher during spring than fall in pectoralis and heart, except that
      fatty acid translocase (FAT/CD36) protein levels showed the opposite pattern in
      heart. Lipid transporter protein levels, but not mRNA expression, in pectoralis
      and heart of warbling vireos were higher either during spring or fall than
      summer, but this was not true for HOAD activities. For yellow warblers,
      pectoralis, but not heart, protein levels of lipid transporters were upregulated
      during migration relative to summer, but this pattern was not evident for mRNA
      expression or HOAD activity. Finally, muscle and heart citrate synthase and
      carnitine palmitoyl transferase activities showed little seasonal variation for
      any species. These data suggest that pectoralis and heart lipid transport and
      catabolism capacities are often, but not universally, important correlates of
      elevated organismal metabolic capacity during migration. In contrast, migration
      induced variation in cellular metabolic intensity and mitochondrial membrane
      transport are apparently not common correlates of the migratory phenotype in
      passerines. 

PMID- 26194863
TI  - Evidence that fibroblast growth factor 10 plays a role in follicle selection in
      cattle.
AB  - There is evidence that regulation of follicle selection in cattle involves
      locally produced growth factors. In the present study, we investigated the
      expression of members of the fibroblast growth factor (FGF) 7 family during
      follicle deviation. The largest and second largest follicles were recovered
      during the second day of a synchronised follicle wave and the future dominant and
      future subordinate follicles were identified based on diameter and cytochrome
      P450, family 19, subfamily A, polypeptide 1 (CYP19A1) mRNA levels in granulosa
      cells. Theca cells of the future dominant follicle contained less mRNA encoding
      FGF7 and FGF10 compared with those from the future subordinate follicle 2.5 days
      after ovulation, before a significant difference between the diameters of the
      future dominant and future subordinate follicles could be observed, but FGF22
      mRNA levels did not change. Levels of mRNA encoding FGF receptors FGFR1B and
      FGFR2B in theca and granulosa cells, respectively, were lower in the future
      dominant follicle compared with the future subordinate follicle. Addition of
      FGF10 to granulosa cells in vitro significantly decreased oestradiol secretion,
      as well as CYP19A1, FSH receptor (FSHR) and insulin-like growth factor 1 receptor
      (IGF1R) mRNA abundance, whereas FGF22 had no effect. We conclude that FGF10 and
      FGFR2B expression is increased in the future subordinate follicle before
      morphological deviation, which may contribute to follicle selection.

PMID- 26194864
TI  - miR-203 suppression in gastric carcinoma promotes Slug-mediated cancer
      metastasis.
AB  - MicroRNAs (miRNAs) play critical roles in tumorigenesis and cancer metastasis.
      Recently, miR-203 was reported as a tumor suppressor microRNA silenced in
      different malignancies including hepatocellular carcinoma, prostate cancer, oral
      cancer, breast cancer, and hematopoietic malignancy, whereas its role in the
      carcinogenesis of gastric carcinoma (GC) has not been evaluated. Here, we
      analyzed the levels of miR-203 and Slug in the GC specimen and studied their
      correlation. We analyzed the binding of miR-203 to the 3'-UTR of Slug messenger
      RNA (mRNA) and its effects on Slug translation by bioinformatics analysis and by
      luciferase-reporter assay, respectively. We modified miR-203 levels in GC cells
      and studied their effects on the cell invasiveness in transwell cell migration
      assay. We found that in GC, miR-203 levels were significantly decreased and Slug
      levels were significantly increased. miR-203 and Slug inversely correlated in
      patients' specimen. Bioinformatic analysis predicted that miR-203 may target the
      3'-UTR of Slug mRNA to inhibit its translation, which was confirmed by luciferase
      reporter assay. Overexpression of miR-203 inhibited Slug and cell invasiveness,
      while depletion of miR-203 increased Slug and cell invasiveness. These data
      suggest that miR-203 suppression in GC promotes Slug-mediated cancer metastasis.

PMID- 26194865
TI  - Inverse regulation of bridging integrator 1 and BCR-ABL1 in chronic myeloid
      leukemia.
AB  - Endocytosis is the major regulator process of tyrosine kinase receptor (RTK)
      functional activities. Bridging integrator 1 (BIN1) is a key protein involved in
      RTK intracellular trafficking. Here, we report, by studying 34 patients with
      chronic myeloid leukemia (CML) at diagnosis, that BIN1 gene is downregulated in
      CML as compared to healthy controls, suggesting an altered endocytosis of RTKs.
      Rab interactor 1 (RIN1), an activator of BIN1, displayed a similar behavior.
      Treatment of 57 patients by tyrosine kinase inhibitors caused, along with BCR
      ABL1 inactivation, an increase of BIN1 and RIN1 expression, potentially restoring
      endocytosis. There was a significant inverse correlation between BIN1-RIN1 and
      BCR-ABL1 expression. In vitro experiments on both CML and nontumorigenic cell
      lines treated with Imatinib confirmed these results. In order to provide another
      proof in favor of BIN1 and RIN1 endocytosis function in CML, we demonstrated that
      Imatinib induced, in K562 cell line, BIN1-RIN1 upregulation accompanied by a
      parallel AXL receptor internalization into cytoplasmic compartment. This study
      shows a novel deregulated mechanism in CML patients, indicating BIN1 and RIN1 as
      players in the maintenance of the abnormal RTK signaling in this hematological
      disease. 

PMID- 26194867
TI  - Protective effect of angiotensin II receptor blocker and calcium channel blocker
      on endothelial vasomotor function after everolimus-eluting stent implantation.
AB  - BACKGROUND: Endothelial dysfunction after drug-eluting stent implantation has
      been demonstrated. It may be associated with adverse cardiovascular events during
      follow-up. Olmesartan, an angiotensin II receptor antagonist, ameliorates
      endothelial dysfunction. The present study evaluated the protective effect of
      olmesartan on endothelial function after everolimus-eluting stent (EES)
      implantation. METHODS: A total of 40 patients who underwent EES implantation were
      randomly assigned to the olmesartan group (20 patients with 30 lesions) or the
      non-olmesartan group (20 patients with 32 lesions). Endothelial function was
      estimated by measuring the coronary vasoreactivity in the segments 15mm proximal
      and distal to EES in response to intracoronary infusion of acetylcholine (Ach;
      10(-8) and 10(-7)mol/L) at 9-month follow-up. Endothelium-independent vasomotion
      was assessed after an intracoronary bolus of isosorbide dinitrate. RESULTS: In
      both groups, Ach infusion did not induce significant vasoconstriction in the
      segment either proximal or distal to the EES. The changes in coronary diameter in
      response to 10(-8)mol/L (-2.0+/-4.4% vs. -0.6+/-4.1%, p=0.33) and 10(-7)mol/L (
      1.8+/-7.9% vs. -0.3+/-7.6%, p=0.57) Ach infusion in the segment proximal to EES
      were not significantly different between the olmesartan group and the non
      olmesartan group. There were no significant differences in vasoconstriction in
      response to 10(-8)mol/L (-0.8+/-5.8% vs. -0.9+/-7.0%, p=0.96) and 10(-7)mol/L
      (1.8+/-9.7% vs. -1.8+/-9.7%, p=0.16) Ach infusion in the segment distal to EES
      between the 2 groups. Endothelium-independent vasodilation after nitrate infusion
      did not differ between the 2 groups. CONCLUSIONS: Endothelial dysfunction is not
      observed after EES implantation. Olmesartan does not improve endothelial function
      after EES implantation.

PMID- 26194866
TI  - Hesperidin from Citrus seed induces human hepatocellular carcinoma HepG2 cell
      apoptosis via both mitochondrial and death receptor pathways.
AB  - Citrus seeds are full of phenolic compounds, such as flavonoids. The aims of this
      study were to identify the types of flavonoids in Citrus seed extracts, the
      cytotoxic effect, mode of cell death, and signaling pathway in human hepatic
      cancer HepG2 cells. The flavonoids contain anticancer, free radical scavenging,
      and antioxidant activities. Neohesperidin, hesperidin, and naringin, active
      flavanone glycosides, were identified in Citrus seed extract. The cytotoxic
      effect of three compounds was in a dose-dependent manner, and IC50 levels were
      determined. The sensitivity of human HepG2 cells was as follows: hesperidin >
      naringin > neohesperidin > naringenin. Hesperidin induced HepG2 cells to undergo
      apoptosis in a dose-dependent manner as evidenced by the externalization of
      phosphatidylserine and determined by annexin V-fluorescein isothiocyanate and
      propidium iodide staining using flow cytometry. Hesperidin did not induce the
      generation of reactive oxygen species, which was determined by using 2',7'
      dichlorohydrofluorescein diacetate and flow cytometry method. The number of
      hesperidin-treated HepG2 cells with the loss of mitochondrial transmembrane
      potential increased concentration dependently, using 3,3'-dihexyloxacarbocyanine
      iodide employing flow cytometry. Caspase-9, -8, and -3 activities were activated
      and increased in hesperidin-treated HepG2 cells. Bcl-xL protein was downregulated
      whereas Bax, Bak, and tBid protein levels were upregulated after treatment with
      hesperidin in a dose-dependent manner. In conclusion, the bioflavanone from
      Citrus seeds, hesperidin, induced human HepG2 cell apoptosis via mitochondrial
      pathway and death receptor pathway. Citrus seed flavonoids are beneficial and can
      be developed as anticancer drug or food supplement, which still needs further in
      vivo investigation in animals and human beings. 

PMID- 26194869
TI  - Platelet refractoriness--practical approaches and ongoing dilemmas in patient
      management.
AB  - Platelet refractoriness can represent a significant clinical problem that
      complicates the provision of platelet transfusions, is associated with adverse
      clinical outcomes and increases health care costs. Although it is most frequently
      due to non-immune platelet consumption, immunological factors are also often
      involved. Human leucocyte antigen (HLA) alloimmunization is the most important
      immune cause. Despite the fact that systematic reviews of the clinical studies
      evaluating different techniques for selecting HLA compatible platelets have not
      been powered to demonstrate improved clinical outcomes, platelet refractoriness
      is currently managed by the provision of HLA-matched or cross matched platelets.
      This review will address a practical approach to the diagnosis and management of
      platelet refractoriness while highlighting on-going dilemmas and knowledge gaps. 

PMID- 26194868
TI  - Stabilization of atherosclerotic plaque by pitavastatin in Watanabe heritable
      hyperlipidemic rabbits: A serial tissue-characterizing intravascular ultrasound
      study.
AB  - BACKGROUND: To examine the effects of pitavastatin on atherosclerotic plaque in
      Watanabe heritable hyperlipidemic (WHHL) rabbits using serial in vivo tissue
      characterizing intravascular ultrasound. METHODS: A total of 11 WHHL rabbits of
      10-12 weeks of age were divided into two groups, control and pitavastatin
      administered groups. A total of 29 atherosclerotic plaque segments from control
      group and 43 plaque segments from the pitavastatin group were serially imaged by
      40MHz intravascular ultrasound in vivo with a tissue characterization software
      (iMAPTM, Boston Scientific, Natick, MA, USA) at the baseline and the follow-up
      (16th week). RESULTS: The level of low-density lipoprotein cholesterol was
      significantly decreased in pitavastatin group. During the follow-up period,
      plaque area was significantly increased in the control group, whereas it was not
      significantly changed in the pitavastatin group. The fibrotic, necrotic, and
      necrotic plus lipidic areas were significantly increased in the control group,
      while no significant change was revealed for tissue profile in pitavastatin
      group. The change in the percent areas of fibrotic and lipidic plus necrotic
      tissues were significantly different between the two groups especially in the
      superficial half portion of plaque. CONCLUSIONS: These data indicate that
      pitavastatin could attenuate atherosclerotic plaque formation and that it could
      stabilize the plaque in WHHL rabbits. Considering the fact that these were
      observed even with a high follow-up level of cholesterol, these data might come
      from the pleiotropic effects of pitavastatin.

PMID- 26194870
TI  - Nanomaterials, Autophagy, and Lupus Disease.
AB  - Nanoscale materials hold great promise in the therapeutic field. In particular,
      as carriers or vectors, they help bioactive molecules reach their primary
      targets. Furthermore, by themselves, certain nanomaterials-regarded as protective
      can modulate particular metabolic pathways that are deregulated in pathological
      situations. They can also synergistically improve the effects of a payload drug.
      These properties are the basis of their appeal. However, nanoscale materials can
      also have intrinsic properties that limit their use, and this is the case for
      certain types of nanomaterials that influence autophagy. This property can be
      beneficial in some pathological settings, but in others, if the autophagic flux
      is already accelerated, it can be deleterious. This is notably the case for
      systemic lupus erythematosus (SLE) and other chronic inflammatory diseases,
      including certain neurological diseases. The nanomaterial-autophagy interaction
      therefore must be treated with caution for therapeutic molecules and peptides
      that require vectorization for their administration. 

PMID- 26194871
TI  - Professional ethics in extreme circumstances: responsibilities of attending
      physicians and healthcare providers in hunger strikes.
AB  - Hunger strikes potentially present a serious challenge for attending physicians.
      Though rare, in certain cases, a conflict can occur between the obligations of
      beneficence and autonomy. On the one hand, physicians have a duty to preserve
      life, which entails intervening in a hunger strike before the hunger striker
      loses his life. On the other hand, physicians' duty to respect autonomy implies
      that attending physicians have to respect hunger strikers' decisions to refuse
      nutrition. International medical guidelines state that physicians should follow
      the strikers' unpressured advance directives. When physicians encounter an
      unconscious striker, in the absence of reliable advance directives, the
      guidelines advise physicians to make a decision on the basis of the patient's
      values, previously expressed wishes, and best interests. I argue that if there
      are no advance directives and the striker has already lost his competence, the
      physician has the responsibility to resuscitate the striker. Once the striker
      regains his decision-making capacity, he should be asked about his decision. If
      he is determined to continue fasting and refuses treatment, the physician has a
      moral obligation to respect this decisions and follow his advance directives. 

PMID- 26194872
TI  - Biomembranes in atomistic and coarse-grained simulations.
AB  - The architecture of biological membranes is tightly coupled to the localization,
      organization, and function of membrane proteins. The organelle-specific
      distribution of lipids allows for the formation of functional microdomains (also
      called rafts) that facilitate the segregation and aggregation of membrane
      proteins and thus shape their function. Molecular dynamics simulations enable to
      directly access the formation, structure, and dynamics of membrane microdomains
      at the molecular scale and the specific interactions among lipids and proteins on
      timescales from picoseconds to microseconds. This review focuses on the latest
      developments of biomembrane force fields for both atomistic and coarse-grained
      molecular dynamics (MD) simulations, and the different levels of coarsening of
      biomolecular structures. It also briefly introduces scale-bridging methods
      applicable to biomembrane studies, and highlights selected recent applications.

PMID- 26194873
TI  - GPs must redesign Health Check programme if they want it to work, conference
      hears.

PMID- 26194874
TI  - Kinematic analysis of reaching movements of the upper limb after total or reverse
      shoulder arthroplasty.
AB  - Studies have analyzed three-dimensional complex motion of the shoulder in healthy
      subjects or patients undergoing total shoulder arthroplasty (TSA) or reverse
      shoulder arthroplasty (RSA). No study to date has assessed the reaching movements
      in patients with TSA or RSA. Twelve patients with TSA (Group A) and 12 with RSA
      (Group B) underwent kinematic analysis of reaching movements directed at four
      targets. The results were compared to those of 12 healthy subjects (Group C). The
      assessed parameters were hand-to-target distance, target-approaching velocity,
      humeral-elevation angular velocity, normalized jerk (indicating motion fluidity),
      elbow extension and humeral elevation angles. Mean Constant score increased by 38
      points in Group A and 47 in Group B after surgery. In three of the tasks, there
      were no significant differences between healthy subjects and patients in the
      study groups. Mean target-approaching velocity and humeral-elevation angular
      velocity were significantly greater in the control group than in study groups
      and, overall, greater in Group A than Group B. Movement fluidity was
      significantly greater in the controls, with patients in Group B showing greater
      fluidity than those in Group A. Reaching movements in the study groups were
      comparable, in three of the tasks, to those in the control group. However, the
      latter performed significantly better with regard to target-approaching velocity,
      humeral-elevation angular velocity and movement fluidity, which are the most
      representative characteristics of reaching motion. These differences, that may be
      related to deterioration of shoulder proprioception after prosthetic implant,
      might possibly be decreased with appropriate rehabilitation. 

PMID- 26194875
TI  - Topological data analysis of contagion maps for examining spreading processes on
      networks.
AB  - Social and biological contagions are influenced by the spatial embeddedness of
      networks. Historically, many epidemics spread as a wave across part of the
      Earth's surface; however, in modern contagions long-range edges-for example, due
      to airline transportation or communication media-allow clusters of a contagion to
      appear in distant locations. Here we study the spread of contagions on networks
      through a methodology grounded in topological data analysis and nonlinear
      dimension reduction. We construct 'contagion maps' that use multiple contagions
      on a network to map the nodes as a point cloud. By analysing the topology,
      geometry and dimensionality of manifold structure in such point clouds, we reveal
      insights to aid in the modelling, forecast and control of spreading processes.
      Our approach highlights contagion maps also as a viable tool for inferring low
      dimensional structure in networks. 

PMID- 26194876
TI  - Is the regulation of the electronic properties of organic molecules by
      polynuclear superhalogens more effective than that by mononuclear superhalogens?
      A high-level ab initio case study.
AB  - The regulation of the electronic properties of organic molecules induced by
      polynuclear superhalogens is theoretically explored here for sixteen composite
      structures. It is clearly indicated by the higher vertical electron detachment
      energy (VDE) that polynuclear superhalogens are more effective in regulating the
      electronic properties than mononuclear structures. However, this enhanced
      regulation is not only determined by superhalogens themselves but also related to
      the distribution of the extra electron of the final composites. The composites,
      in which the extra electron is mainly aggregated into the superhalogen moiety,
      will possess higher VDE values, as reported in the case of C1', 7.12 eV at the
      CCSD(T) level. This is probably due to the fact that, compared with organic
      molecules, superhalogens possess stronger attraction towards the extra electron
      and thus should lead to lower energies of the extra electrons and to higher VDE
      values eventually. Compared with CCSD(T), the Outer Valence Green's Function
      (OVGF) method fails completely for composite structures containing Cl atoms,
      while MP2 results are generally consistent in terms of the relative order of
      VDEs. Actually if the extra electron distribution of the systems could be
      approximated by the HOMO, the results at the OVGF level will be consistent with
      the CCSD(T) results. Conversely, the difference in VDEs between OVGF and CCSD(T)
      is significantly large. Besides superhalogen properties, the structures, relative
      stabilities and thermodynamic stabilities with respect to various fragmentation
      channels were also investigated for all the composite structures.

PMID- 26194877
TI  - Synthesis of o-Carboxyarylacrylic Acids by Room Temperature Oxidative Cleavage of
      Hydroxynaphthalenes and Higher Aromatics with Oxone.
AB  - A simple procedure for the synthesis of a variety of o-carboxyarylacrylic acids
      has been developed with Oxone (2KHSO5.KHSO4.K2SO4); the oxidation reaction
      involves the stirring of methoxy/hydroxy-substituted naphthalenes, phenanthrenes,
      anthracenes, etc. with Oxone in an acetonitrile-water mixture (1:1, v/v) at rt.
      Mechanistically, the reaction proceeds via initial oxidation of naphthalene to o
      quinone, which undergoes cleavage to the corresponding o-carboxyarylacrylic acid.
      The higher aromatics are found to yield carboxymethyl lactones derived from the
      initially formed o-carboxyarylacrylic acids. 

PMID- 26194879
TI  - Bisphenol A and its structural analogues in household waste paper.
AB  - Bisphenol A (BPA) is an industrial chemical produced in large volumes. Its main
      use is associated with polycarbonate plastic, epoxy resins and thermal paper. In
      contrast to other applications, thermal paper contains BPA in its un-reacted form
      as an additive, which is subjected to migration. Receiving a significant amount
      of attention from the scientific community and beyond, due to its controversial
      endocrine-disrupting effects, the industry is attempting to substitute BPA in
      variety of applications. Alternative phenolic compounds have been proposed for
      use in thermal paper; however, information to what extent BPA alternatives have
      been used in paper is sparse. The aim of the present work was to quantify BPA and
      its alternatives (bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB), 4
      cumylphenol (HPP) and bisphenol F (BPF)) in waste paper and board from Danish
      households, thermal paper receipts, non-carbon copy paper and conventional
      printer paper. BPA was found in all waste paper samples analysed, while BPS was
      identified in 73% of them. Only BPB was not identified in any of the samples. BPA
      and BPS were found in the majority of the receipts, which contained no measurable
      concentrations of the remaining alternatives. Although receipts showed the
      highest concentrations of BPA and BPS, office paper, flyers and corrugated boxes,
      together with receipts, represented the major flux of the two compounds in waste
      paper streams. 

PMID- 26194878
TI  - Clinical relevance of copy number profiling in oral and oropharyngeal squamous
      cell carcinoma.
AB  - Current conventional treatment modalities in head and neck squamous cell
      carcinoma (HNSCC) are nonselective and have shown to cause serious side effects.
      Unraveling the molecular profiles of head and neck cancer may enable promising
      clinical applications that pave the road for personalized cancer treatment. We
      examined copy number status in 36 common oncogenes and tumor suppressor genes in
      a cohort of 191 oropharyngeal squamous cell carcinomas (OPSCC) and 164 oral
      cavity squamous cell carcinomas (OSCC) using multiplex ligation probe
      amplification. Copy number status was correlated with human papillomavirus (HPV)
      status in OPSCC, with occult lymph node status in OSCC and with patient survival.
      The 11q13 region showed gain or amplifications in 59% of HPV-negative OPSCC,
      whereas this amplification was almost absent in HPV-positive OPSCC. Additionally,
      in clinically lymph node-negative OSCC (Stage I-II), gain of the 11q13 region was
      significantly correlated with occult lymph node metastases with a negative
      predictive value of 81%. Multivariate survival analysis revealed a significantly
      decreased disease-free survival in both HPV-negative and HPV-positive OPSCC with
      a gain of Wnt-induced secreted protein-1. Gain of CCND1 showed to be an
      independent predictor for worse survival in OSCC. These results show that copy
      number aberrations, mainly of the 11q13 region, may be important predictors and
      prognosticators which allow for stratifying patients for personalized treatment
      of HNSCC. 

PMID- 26194880
TI  - Effectiveness of Using Mobile Phone Image Capture for Collecting Secondary Data:
      A Case Study on Immunization History Data Among Children in Remote Areas of
      Thailand.
AB  - BACKGROUND: Entering data onto paper-based forms, then digitizing them, is a
      traditional data-management method that might result in poor data quality,
      especially when the secondary data are incomplete, illegible, or missing.
      Transcription errors from source documents to case report forms (CRFs) are
      common, and subsequently the errors pass from the CRFs to the electronic
      database. OBJECTIVE: This study aimed to demonstrate the usefulness and to
      evaluate the effectiveness of mobile phone camera applications in capturing
      health-related data, aiming for data quality and completeness as compared to
      current routine practices exercised by government officials. METHODS: In this
      study, the concept of "data entry via phone image capture" (DEPIC) was introduced
      and developed to capture data directly from source documents. This case study was
      based on immunization history data recorded in a mother and child health (MCH)
      logbook. The MCH logbooks (kept by parents) were updated whenever parents brought
      their children to health care facilities for immunization. Traditionally, health
      providers are supposed to key in duplicate information of the immunization
      history of each child; both on the MCH logbook, which is returned to the parents,
      and on the individual immunization history card, which is kept at the health care
      unit to be subsequently entered into the electronic health care information
      system (HCIS). In this study, DEPIC utilized the photographic functionality of
      mobile phones to capture images of all immunization-history records on logbook
      pages and to transcribe these records directly into the database using a data
      entry screen corresponding to logbook data records. DEPIC data were then compared
      with HCIS data-points for quality, completeness, and consistency. RESULTS: As a
      proof-of-concept, DEPIC captured immunization history records of 363 ethnic
      children living in remote areas from their MCH logbooks. Comparison of the 2
      databases, DEPIC versus HCIS, revealed differences in the percentage of
      completeness and consistency of immunization history records. Comparing the
      records of each logbook in the DEPIC and HCIS databases, 17.3% (63/363) of
      children had complete immunization history records in the DEPIC database, but no
      complete records were reported in the HCIS database. Regarding the individual's
      actual vaccination dates, comparison of records taken from MCH logbook and those
      in the HCIS found that 24.2% (88/363) of the children's records were absolutely
      inconsistent. In addition, statistics derived from the DEPIC records showed a
      higher immunization coverage and much more compliance to immunization schedule by
      age group when compared to records derived from the HCIS database. CONCLUSIONS:
      DEPIC, or the concept of collecting data via image capture directly from their
      primary sources, has proven to be a useful data collection method in terms of
      completeness and consistency. In this study, DEPIC was implemented in data
      collection of a single survey. The DEPIC concept, however, can be easily applied
      in other types of survey research, for example, collecting data on changes or
      trends based on image evidence over time. With its image evidence and audit trail
      features, DEPIC has the potential for being used even in clinical studies since
      it could generate improved data integrity and more reliable statistics for use in
      both health care and research settings.

PMID- 26194881
TI  - Usability and utility of the CONSORT calculator for FSH starting doses: a
      prospective observational study.
AB  - This prospective, multicentre, observational study assessed usability and utility
      (co-primary endpoints) of the consistency in r-hFSH starting doses for
      individualized treatment (CONSORT) calculator in French routine clinical
      practice. Physicians first planned their recombinant human follicle-stimulating
      hormone (r-hFSH) starting dose. The CONSORT calculator was then used to recommend
      a starting dose. Data were collected for 197 women aged 18-35 years undergoing
      ovarian stimulation. The usability rate was high: 44/45 (97.8%) physicians found
      CONSORT user-friendly and easy to use for >=75% of patients. Utility data showed
      that physicians followed the CONSORT recommendation for 89/197 (45.2%) patients.
      Reasons given for not following the CONSORT-calculated dose (N = 108) included:
      the CONSORT-calculated dose was too divergent from the planned dose (48.1%;
      52/108) and/or the CONSORT-calculated dose did not correspond to the patient
      profile (46.3%; 50/108). The mean +/- SD starting dose of r-hFSH planned by
      physicians was 163.9 +/- 51.2 IU; the mean (SD) starting dose recommended by the
      CONSORT calculator was 119.7 +/- 20.9 IU and the mean (SD) dose actually
      prescribed to patients was 151.7 +/- 51.1 IU. Despite low physician-reported
      utility in this study, post-hoc analyses suggest the CONSORT calculator has
      potential for use in routine clinical practice.

PMID- 26194882
TI  - Live births achieved via IVF are increased by improvements in air quality and
      laboratory environment.
AB  - Infertility is a common disease, which causes many couples to seek treatment with
      assisted reproduction techniques. Many factors contribute to successful assisted
      reproduction technique outcomes. One important factor is laboratory environment
      and air quality. Our facility had the unique opportunity to compare consecutively
      used, but separate assisted reproduction technique laboratories, as a result of a
      required move. Environmental conditions were improved by strategic engineering
      designs. All other aspects of the IVF laboratory, including equipment,
      physicians, embryologists, nursing staff and protocols, were kept constant
      between facilities. Air quality testing showed improved air quality at the new
      IVF site. Embryo implantation (32.4% versus 24.3%; P < 0.01) and live birth
      (39.3% versus 31.8%, P < 0.05) were significantly increased in the new facility
      compared with the old facility. More patients met clinical criteria and underwent
      mandatory single embryo transfer on day 5 leading to both a reduction in multiple
      gestation pregnancies and increased numbers of vitrified embryos per patient with
      supernumerary embryos available. Improvements in IVF laboratory conditions and
      air quality had profound positive effects on laboratory measures and patient
      outcomes. This study further strengthens the importance of the laboratory
      environment and air quality in the success of an IVF programme. 

PMID- 26194883
TI  - Contrasting effects of G1.2/G2.2 and SOF1/SOF2 embryo culture media on pre- and
      post-implantation development of non-transgenic and transgenic cloned goat
      embryos.
AB  - This study compared the efficiency of two embryo culture media (SOF1/SOF2 and
      G1.2/G2.2) for pre- and post-implantation development of somatic cell nuclear
      transfer goat embryos derived from non-transgenic and transgenic (for htPA and
      hrcfIX genes) fibroblasts. Despite similar cleavage rates, G1.2/G2.2 supported
      significantly higher blastocyst development than SOF1/SOF2 (30-35% versus 21%; P
      < 0.05), irrespective of cell transgenesis. However, following embryo transfer,
      pregnancy outcomes (establishment, full-term development and live birth) were all
      significantly higher (P < 0.05) for embryos developed in SOF1/SOF2 versus
      G1.2/G2.2. Gene expression profiling of 17 developmentally important genes
      revealed that: (i) SOX2, FOXD3, IFNT, FZD, FGFR4, ERK1, GCN5, PCAF, BMPR1, SMAD5,
      ALK4, CDC25 and LIFR were significantly induced in blastocysts developed in
      SOF1/SOF2 but not G1.2/G2.2; (ii) OCT4, CTNNB and CDX2 were similarly expressed
      in both groups; and (iii) AKT was significantly higher in G1.2/G2.2 than
      SOF1/SOF2 (P < 0.05). Following IVF, although blastocyst development in G1.2/G2.2
      was significantly higher than SOF1/SOF2 counterparts, the majority of assessed
      genes were similarly expressed in blastocysts developed in both groups. It was
      concluded that the long-term programming effects of embryo culture medium and/or
      embryo production method may irreversibly affect post-implantation development of
      cloned embryos through defined molecular pathways. 

PMID- 26194884
TI  - Randomized trial comparing luteinizing hormone supplementation timing strategies
      in older women undergoing ovarian stimulation.
AB  - In this open-label study, women aged 36-40 years undergoing ovarian stimulation
      were randomized to recombinant human FSH (rhFSH) plus recombinant human
      luteinizing hormone (rhLH) from stimulation day 1 (group A; n = 103), or rhFSH
      alone (days 1-5) followed by rhFSH plus rhLH from day 6 (group B; n = 99). The
      primary objective was equivalence in number of oocytes retrieved per patient. The
      mean (+/-SD) number of oocytes retrieved was 9.7 (+/-6.9) in group A and 10.9 (+/
      6.5) in group B; the estimated difference between groups (-1.28 oocytes [95%
      confidence interval: -3.15 to 0.59]) did not reach the predefined limit of
      equivalence (+/-3 oocytes). The study's primary objective was therefore not met.
      In both groups, a mean (+/-SD) of 1.9 (+/-0.6) embryos were transferred per
      patient. Implantation rates were 24.7% in group A and 13.3% in group B. Clinical
      pregnancy rates per started cycle and per embryo transfer were 31.6% and 34.4% in
      Group A, 17.2% and 18.9% in Group B. Ovarian hyperstimulation syndrome was
      reported in four (group A) and five (group B) patients. The potential benefit of
      initiating LH supplementation earlier during ovarian stimulation in older women
      is of interest, warranting further exploration. 

PMID- 26194885
TI  - Mmu-miR-126a-3p plays a role in murine embryo implantation by regulating Itga11.
AB  - miR-126a-3p has been found to be specifically up-regulated in the process of
      murine embryo implantation. This study aimed to further clarify the role of miR
      126a-3p in embryo implantation. The expression of miR-126a-3p in implantation
      sites was significantly higher than that in interimplantation sites (P = 0.009).
      Its expression dynamics in a series of models, including pseudopregnancy, delayed
      implantation and artificial decidualization, suggested that the induction of miR
      126a-3p is dependent on hormonal signalling and decidualization of the
      endometrium. Bioinformatic analysis predicted and luciferase activity assay
      confirmed that Itga11, a member of the integrin family, was a target gene of miR
      126a-3p. miR-126a-3p bound to the 3' untranslated region of Itga11 and regulated
      Itga11 by inhibiting mRNA translation and affecting mRNA stability. Transwell
      assay showed that miR-126a-3p promoted cell migratory and invasive capacity in
      vitro. Loss of function of miR-126a-3p significantly reduced the number of
      implantation sites in vivo (P = 0.013). Collectively, miR-126a-3p may play a
      major role in embryo implantation by regulating Itga11, possibly through
      impairing cell migratory and invasive capacity. These findings should contribute
      to a better understanding of the miRNA-based mechanism of embryo implantation. 

PMID- 26194886
TI  - In-vitro effects of Thymus munbyanus essential oil and thymol on human sperm
      motility and function.
AB  - Traditional medicine has been used worldwide for centuries to cure or prevent
      disease and for male or female contraception. Only a few studies have directly
      investigated the effects of herbal compounds on spermatozoa. In this study,
      essential oil from Thymus munbyanus was extracted and its effect on human
      spermatozoa in vitro was analysed. Gas chromatography and Gas chromatography-mass
      spectrometry analyses identified 64 components, accounting for 98.9% of the
      composition of the oil. The principal components were thymol (52.0%), gamma
      terpinene (11.0%), rho-cymene (8.5%) and carvacrol (5.2%). Freshly ejaculated
      spermatozoa was exposed from control individuals to various doses of the
      essential oil for different time periods, and recorded the vitality, the mean
      motility, the movement characteristics (computer-aided sperm analysis), the
      morphology and the ability to undergo protein hyperphosphorylation and acrosomal
      reaction, which constitute two markers of sperm capacitation and fertilizing
      ability. In vitro, both the essential oil extracted from T. munbyanus and thymol,
      the principal compound present in this oil, impaired human sperm motility and its
      capacity to undergo hyperphosphorylation and acrosome reaction. These compounds
      may, therefore, be of interest in the field of reproductive biology, as potential
      anti-spermatic agents. 

PMID- 26194887
TI  - The codon 72 polymorphism of the TP53 gene and endometriosis risk: a meta
      analysis.
AB  - Endometriosis is a chronic, inflammatory and common gynaecological disease. This
      study investigated the association between TP53 codon 72 polymorphism and the
      risk of endometriosis. A search for relevant articles was conducted in PubMed,
      Embase, CNKI, Wanfang, Weipu databases and Google Scholar. The strength of the
      relationships between TP53 codon 72 polymorphism and the risk of endometriosis
      was assessed by odds ratios (OR) and with 95% confidence intervals (CI). Sixteen
      case-control studies in 15 articles were included. Significant association was
      found in the dominant model (CC + GC versus GG) with an OR of 1.38 and 95% CI
      (1.14, 1.67). The results suggested that individuals who carried CC homozygote
      and heterozygote GC might have a 38% increased endometriosis risk when compared
      with the homozygote GG. In the subgroup analysis by ethnicity, significantly
      increased risk was observed among Asians (OR = 1.62, 95% CI = 1.18-2.23, P =
      0.003) and Latin Americans (OR = 1.54, 95% CI = 1.16-2.03, P = 0.002) but not in
      Caucasians (OR = 1.02, 95% CI = 0.80-1.30) for the dominant model. The current
      meta-analysis suggested that TP53 codon 72 polymorphism was associated with the
      endometriosis risk, especially in Asians and Latin Americans. 

PMID- 26194888
TI  - A microfluidic device to study neuronal and motor responses to acute chemical
      stimuli in zebrafish.
AB  - Zebrafish larva is a unique model for whole-brain functional imaging and to study
      sensory-motor integration in the vertebrate brain. To take full advantage of this
      system, one needs to design sensory environments that can mimic the complex
      spatiotemporal stimulus patterns experienced by the animal in natural conditions.
      We report on a novel open-ended microfluidic device that delivers pulses of
      chemical stimuli to agarose-restrained larvae with near-millisecond switching
      rate and unprecedented spatial and concentration accuracy and reproducibility. In
      combination with two-photon calcium imaging and recordings of tail movements, we
      found that stimuli of opposite hedonic values induced different circuit activity
      patterns. Moreover, by precisely controlling the duration of the stimulus (50-500
      ms), we found that the probability of generating a gustatory-induced behavior is
      encoded by the number of neurons activated. This device may open new ways to
      dissect the neural-circuit principles underlying chemosensory perception.

PMID- 26194889
TI  - Rivaroxaban versus high dose nadroparin for thromboprophylaxis after hip or knee
      arthroplasty.
AB  - Deep-vein thrombosis and subsequent pulmonary embolism are major complications in
      total joint arthroplasty of the lower limbs. New oral anticoagulants are
      increasingly prescribed as thromboprophylaxis due to their simple administration
      and encouraging phase III marketing studies. PATIENTS, METHODS: In this
      observational study, we compared the efficacy and safety of rivaroxaban with
      nadroparin in 1302 unselected patients receiving hip or knee arthroplasty.
      RESULTS: Venous thrombembolism occurred in 3.3% (2.3%; 4.7%, 95% CI, n = 838) of
      patients receiving rivaroxaban and in 4.3% (2.7%; 6.7%, 95% CI, n = 464) of
      patients receiving nadroparin resulting in an absolute risk reduction (ARR) of
      1.0% (-1.4%; 3.3%, 95% CI). CONCLUSIONS: With an odds ratio of 0.6 (0.4; 1.0, 95%
      CI), rivaroxaban was associated with a decreased perioperative drop in
      haemoglobin exhibiting an improved thromboprophylactic profile when compared to
      high dose nadroparin. Furthermore, transfusion rates were 8.8% (-2.7%; 19.9%, 95%
      CI) lower in patients receiving rivaroxaban. However, as previous studies have
      shown, low preoperative haemoglobin remains the most predictive factor for
      postoperative transfusions (OR: 2.4 [1.3; 4.4, 95% CI]).

PMID- 26194890
TI  - Assessing health status in informal schizophrenia caregivers compared with health
      status in non-caregivers and caregivers of other conditions.
AB  - BACKGROUND: Research indicates schizophrenia is a cause of burden for patients
      and caregivers. This study examined health-related quality of life (HRQoL) and
      comorbidities experienced by informal schizophrenia caregivers compared with non
      caregivers and caregivers of adults with other conditions (e.g., Alzheimer's
      disease, cancer, and stroke). METHODS: Data were obtained from the 5EU (France,
      Germany, Italy, Spain, UK) National Health and Wellness Survey, an online
      questionnaire that is representative of the total 5EU adult (18+ years)
      population. Respondents provided information on HRQoL (SF-36v2: mental and
      physical component summary (MCS, PCS) and SF-6D (health utility) scores), items
      from the Caregiver Reaction Assessment (strongly disagree to strongly agree) and
      comorbidities (sleep difficulties, insomnia, pain, headaches, heartburn, anxiety,
      depression) experienced in the past 12 months. Schizophrenia caregivers (n = 398)
      were matched to non-caregivers (n = 158,989) and caregivers of other conditions
      (n = 14,341) on baseline characteristics via propensity scores. Chi-square tests
      and ANOVAs were used to determine significant differences across groups. RESULTS:
      The average age of schizophrenia caregivers was 45.3 years (SD = 15.8), and 59.6%
      were female. After matching, schizophrenia caregivers reported lower MCS (40.3
      vs. 45.9), PCS (46.8 vs. 49.0), and health utilities (0.64 vs. 0.71) compared
      with non-caregivers (all p < 0.001). Schizophrenia caregivers were more likely to
      experience sleep difficulties (42.7% vs. 28.5%), insomnia (32.4% vs. 18.5%), pain
      (39.7% vs. 30.4%), headaches (48.0% vs. 42.0%), heartburn (31.7% vs. 22.9%),
      anxiety (37.9% vs. 23.6%), and depression (29.4% vs. 19.4%) than non-caregivers.
      Comparing schizophrenia caregivers and other caregivers, schizophrenia caregivers
      reported lower MCS (40.3 vs. 42.7, p < 0.001), and health utilities (0.64 vs.
      0.67, p < 0.001). Schizophrenia caregivers were more likely to experience sleep
      difficulties, insomnia, pain, and anxiety than other caregivers. Almost 60% of
      schizophrenia caregivers agree/strongly agree that caring for the patient is
      important to them, but only 31.9% agree/strongly agree that they have the
      financial resources to provide adequate care. CONCLUSIONS: Schizophrenia
      caregivers reported worse HRQoL than non-caregivers and caregivers of other
      conditions. Providing care for an adult relative with schizophrenia is important
      to caregivers, but caregivers need more resources to provide adequate care.
      Providing informal schizophrenia caregivers with support services to help better
      manage patients may improve their health status.

PMID- 26194891
TI  - Translational Rodent Paradigms to Investigate Neuromechanisms Underlying
      Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia.
AB  - Amotivation and reward-processing deficits have long been described in patients
      with schizophrenia and considered large contributors to patients' inability to
      integrate well in society. No effective treatments exist for these symptoms,
      partly because the neuromechanisms mediating such symptoms are poorly understood.
      Here, we propose a translational neuroscientific approach that can be used to
      assess reward/motivational deficits related to the negative symptoms of
      schizophrenia using behavioral paradigms that can also be conducted in
      experimental animals. By designing and using objective laboratory behavioral
      tools that are parallel in their parameters in rodents and humans, the
      neuromechanisms underlying behaviors with relevance to these symptoms of
      schizophrenia can be investigated. We describe tasks that measure the motivation
      of rodents to expend physical and cognitive effort to gain rewards, as well as
      probabilistic learning tasks that assess both reward learning and feedback-based
      decision making. The latter tasks are relevant because of demonstrated links of
      performance deficits correlating with negative symptoms in patients with
      schizophrenia. These tasks utilize operant techniques in order to investigate
      neural circuits targeting a specific domain across species. These tasks therefore
      enable the development of insights into altered mechanisms leading to negative
      symptom-relevant behaviors in patients with schizophrenia. Such findings will
      then enable the development of targeted treatments for these altered
      neuromechanisms and behaviors seen in schizophrenia. 

PMID- 26194892
TI  - Aberrant Salience Is Related to Dysfunctional Self-Referential Processing in
      Psychosis.
AB  - BACKGROUND: A dysfunctional differentiation between self-relevant and irrelevant
      information may affect the perception of environmental stimuli as abnormally
      salient. The aberrant salience hypothesis assumes that positive symptoms arise
      from an attribution of salience to irrelevant stimuli accompanied by the feeling
      of self-relevance. Self-referential processing relies on the activation of
      cortical midline structures which was demonstrated to be impaired in psychosis.
      We investigated the neural correlates of self-referential processing, aberrant
      salience attribution, and the relationship between these 2 measures across the
      psychosis continuum. METHODS: Twenty-nine schizophrenia patients, 24 healthy
      individuals with subclinical delusional ideation, and 50 healthy individuals
      participated in this study. Aberrant salience was assessed behaviorally in terms
      of reaction times to task irrelevant cues. Participants performed a self
      reference task during fMRI in which they had to apply neutral trait words to them
      or to a public figure. The correlation between self-referential processing and
      aberrant salience attribution was tested. RESULTS: Schizophrenia patients
      displayed increased aberrant salience attribution compared with healthy controls
      and individuals with subclinical delusional ideation, while the latter exhibited
      intermediate aberrant salience scores. In the self-reference task, schizophrenia
      patients showed reduced activation in the ventromedial prefrontal cortex (vmPFC),
      but individuals with subclinical delusional ideation did not differ from healthy
      controls. In schizophrenia patients, vmPFC activation correlated negatively with
      implicit aberrant salience attribution. CONCLUSIONS: Higher aberrant salience
      attribution in schizophrenia patients is related to reduced vmPFC activation
      during self-referential judgments suggesting that aberrant relevance coding is
      reflected in decreased neural self-referential processing as well as in aberrant
      salience attribution.

PMID- 26194893
TI  - Cis-existence of H3K27me3 and H3K36me2 in mouse embryonic stem cells revealed by
      specific ions of isobaric modification chromatogram.
AB  - INTRODUCTION: Histone H3 lysine 27 trimethylation (H3K27me3) and H3 lysine 36
      trimethylation (H3K36me3) are important epigenetic modifications correlated with
      transcription repression and activation, respectively. These two opposing
      modifications rarely co-exist in the same H3 polypeptide. However, a small but
      significant amount of H3 tails are modified with 5 methyl groups on K27 and K36
      in mouse embryonic stem cells (mESCs) and it is unclear how the trimethylation is
      distributed on K27 or K36. METHODS: A label-free, bottom-up mass spectrum method,
      named specific ions of isobaric modification chromatogram (SIMC), was established
      to quantify the relative abundance of K27me2-K36me3 and K27me3-K36me2 in the same
      histone H3 tail. RESULTS: By using this method, we demonstrated that the H3K27me3
      K36me2 comprises about 85 % of the penta-methylated H3 tails at K27 and K36 in
      mESCs. Upon mESC differentiation, the abundance of H3K27me3-K36me2 significantly
      decreased, while the level of H3K27me2-K36me3 remains unchanged. CONCLUSION: Our
      study not only revealed the cis-existence of H3K27me3-K36me2 in mESCs, but also
      suggested that this combinatorial histone modification may assume a specific
      regulatory function during differentiation.

PMID- 26194894
TI  - Patterns and correlates of new psychoactive substance use in a sample of
      Australian high school students.
AB  - INTRODUCTION AND AIMS: In recent years there has been growing concern about new
      psychoactive substances (NPS) designed to mimic the effects of established
      illicit drugs. This paper explores the patterns and correlates of NPS use in a
      sample of Australian students. DESIGN AND METHODS: A cross-sectional survey was
      conducted in Australia in 2014. Data were collected from 1126 students (mean age:
      14.9 years) from 11 secondary schools. Students completed a self-report
      questionnaire assessing NPS use and knowledge, beliefs and intentions to use
      these substances. NPS users were compared with non-users and illicit drug users,
      who had not used NPS, in terms of gender, binge drinking, tobacco use,
      psychological distress and self-efficacy to resist peer pressure. RESULTS: Of the
      1126 students, 3% reported having ever tried NPS, 2.4% had used synthetic
      cannabis and 0.4% had used a synthetic stimulant. Analyses revealed that NPS
      users were more likely to have had an episode of binge drinking in the past 6
      months, tried tobacco and had higher levels of psychological distress and lower
      perceived self-efficacy to resist peer pressure than non-users, but did not
      significantly differ from users of other illicit drugs. DISCUSSION AND
      CONCLUSIONS: NPS use appears to be uncommon among Australian school students.
      Although adolescents that do use these substances did not differ from students
      that had used traditional illicit drugs, both appear to be higher-risk groups of
      students than non-users. Our findings suggest that universal education about NPS
      be incorporated into existing drug prevention programmes, and that targeted NPS
      prevention may also be warranted among high-risk adolescents. [Champion KE,
      Teesson M, Newton NC. Patterns and correlates of new psychoactive substance use
      in a sample of Australian high school students. Drug Alcohol Rev 2016;35:338
      344].

PMID- 26194895
TI  - Predictors of health worker performance after Integrated Management of Childhood
      Illness training in Benin: a cohort study.
AB  - BACKGROUND: Correct treatment of potentially life-threatening illnesses (PLTIs)
      in children under 5 years, such as malaria, pneumonia, and diarrhea, can
      substantially reduce mortality. The Integrated Management of Childhood Illness
      (IMCI) strategy has been shown to improve treatment of child illnesses, but
      multiple studies have shown that gaps in health worker performance remain after
      training. To better understand factors related to health worker performance, we
      analyzed 9,330 patient consultations in Benin from 2001-2002, after training one
      of the first cohorts of 32 health workers in IMCI. METHODS: With data abstracted
      from patient registers specially designed for IMCI-trained health workers, we
      examined associations between health facility-, health worker-, and patient-level
      factors and 10 case-management outcomes for PLTIs. RESULTS: Altogether, 63.6% of
      children received treatment for all their PLTIs in accordance with IMCI
      guidelines, and 77.8% received life-saving treatment (i.e., clinically effective
      treatment, even if not exactly in accordance with IMCI guidelines). Performance
      of individual health workers varied greatly, from 15-88% of patients treated
      correctly, on average. Multivariate regression analyses identified several
      factors that might have influenced case-management quality, many outside a
      manager's direct control. Younger health workers significantly outperformed older
      ones, and infants received better care than older children. Children with danger
      signs, those with more complex illnesses, and those with anemia received worse
      care. Health worker supervision was associated with improved performance for some
      outcomes. CONCLUSIONS: A variety of factors, some outside the direct control of
      program managers, can influence health worker practices. An understanding of
      these influences can help inform the development of strategies to improve
      performance.

PMID- 26194896
TI  - Posterior parasagittal in-plane ultrasound-guided infraclavicular brachial plexus
      block-a case series.
AB  - BACKGROUND: The brachial plexus at the infraclavicular level runs deeper compared
      to its course proximally, giving rise to impaired needle visualisation due to the
      steep angle of needle insertion with the current ultrasound-guided approach. A
      new posterior parasagittal in-plane ultrasound-guided infraclavicular approach
      was introduced to improve needle visibility. However no further follow up study
      was done. METHODS: We performed a case series and a cadaveric dissection to
      assess its feasibility in a single centre, University of Malaya Medical Centre,
      Kuala Lumpur, Malaysia from November 2012 to October 2013. After obtaining
      approval from the Medical Ethics Committee, University Malaya Medical Centre, 18
      patients undergoing upper limb surgery were prospectively recruited. A cadaveric
      dissection was also performed. The endpoints of this study were the success rate,
      performance time, total anaesthesia-related time, quality of anaesthesia and any
      incidence of complications. RESULTS: All patients had 100 % success rate. The
      imaging time, needling time and performance time were comparable with previously
      published study. There were no adverse events encountered in this study. The
      cadaveric dissection revealed a complete spread of methylene blue dye over the
      brachial plexus. CONCLUSION: This study demonstrated that the posterior
      parasagittal in-plane approach is a feasible and reliable technique with high
      success rate. Future studies shall compare this technique with the conventional
      lateral parasagittal in-plane approach. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02312453 . Registered on 8 December 2014.

PMID- 26194897
TI  - Src family kinases maintain the balance between replication stress and the
      replication checkpoint.
AB  - Progression of DNA replication is tightly controlled by replication checkpoints
      to ensure the accurate and rapid duplication of genetic information. Upon
      replication stress, the replication checkpoint slows global DNA replication by
      inhibiting the late-firing origins and by slowing replication fork progression.
      Activation of the replication checkpoint has been studied in depth; however,
      little is known about the termination of the replication checkpoint. Here, we
      show that Src family kinases promote the recovery from replication checkpoints.
      shRNA knockdown of a Src family kinase, Lyn, and acute chemical inhibition of Src
      kinases prevented inactivation of Chk1 after removal of replication stress.
      Consistently, Src inhibition slowed resumption of DNA replication, after the
      removal of replication blocks. The effect of Src inhibition was not observed in
      the presence of an ATM/ATR inhibitor caffeine. These data indicate that Src
      kinases promote the resumption of DNA replication by suppressing ATR-dependent
      replication checkpoints. Surprisingly, the resumption of replication was delayed
      by caffeine. In addition, Src inhibition delayed recovery from replication fork
      collapse. We propose that Src kinases maintain the balance between replication
      stress and the activity of the replication checkpoint.

PMID- 26194898
TI  - Urban and architectural risk factors for malaria in indigenous Amazonian
      settlements in Brazil: a typological analysis.
AB  - In the Amazon, m alaria is highly endemic in indigenous populations, which are
      often considered one of the last barriers to malaria elimination due to
      geographic isolation. Although the improvement of housing conditions is a good
      strategy towards the control and prevention of vector-borne diseases, such as
      malaria, this preventive practice has been barely undertaken in Latin America. An
      analysis of the architectural and urban features of indigenous Amazonian
      populations is essential to define and adapt these vector control measures. A
      total of 32 villages of 29 different ethnicities were studied and mapped by
      reviewing literature and visual information, and using a geographic information
      system. The most important architectural and urban characteristics influencing
      malaria were analysed according to the following categories: number of households
      and dimensions, supporting area, openings, materials, lifespan and location.
      Housing typologies found were classified within each of these variables. The
      results of this typological analysis included an easy-to-handle working template
      and revealing of features that benefit or hamper the presence of malaria vectors
      in Amerindians communities. Among risk factors, presence of open eaves, permeable
      walls, open-side constructions, large number of sleepers indoors, temporary
      ephemeral houses, linear villages along stream banks, houseboats villages, poor
      urban drainage and villages surrounded by anthropogenic environments were
      highlighted. Indigenous settlements very permissive for anophelines were
      identified in ethnic groups, such as the Yanomami, Palikur, Paumari, Waimiri
      Atroari and Wajapi. Positive features were also recognized, including opaque and
      closed houses, large radial villages on bare soil, highly elevated stilted houses
      and the fire indoors, found among the Yawalapiti, Ashaninka, and Gaviao-Parkateje
      tribes. However, as Amazonian indigenous settlement typologies vary greatly even
      among villages of the same ethnic group, it is imperative to undertake an
      individual study for each community. Using the working template in Amazonian
      settlements it is possible to obtain data that will help researchers not only
      understand how architectural and urban features affect transmission, but also
      define vector control measures easily applicable by health authorities and
      acceptable by these communities. 

PMID- 26194899
TI  - Mechanism of the inhibition of leukemia cell growth and induction of apoptosis
      through the activation of ATR and PTEN by the topoisomerase inhibitor 3EZ, 20Ac
      ingenol.
AB  - The PI3K/Akt signaling pathway is constitutively activated in various leukemias.
      In the present study, the topoisomerase inhibitor, 3EZ, 20Ac-ingenol, was more
      effective in inhibiting the growth of BALL-1 cells than that of normal lymphocyte
      cells. ATM/ATR protein levels were increased, PTEN protein was upregulated, and p
      Akt protein was downregulated at early time points after treatment with 3EZ, 20Ac
      ingenol. In further experiments, p53 protein expression was increased, and H2AX
      phosphorylation and p21 protein expression were induced after treatment with 3EZ,
      20Ac-ingenol. Moreover, the activation of caspase 3 followed decrease in the Bcl
      2/Bax ratio after treatment with 3EZ, 20Ac-ingenol, and accumulation of sub-G1
      phase cells was observed in flow cytometry analyses. These data suggest that 3EZ,
      20Ac-ingenol-induced DNA damage downregulates p-Akt and upregulates ATR leading
      to cell cycle arrest and increased apoptosis in BALL-1 cells. 

PMID- 26194901
TI  - Yield and cost-effectiveness of laboratory testing to identify metabolic
      contributors to falls and fractures in older persons.
AB  - Falls and fractures constitute a major cause of morbidity and mortality among
      older adults. Although falls and fractures share similar risk factors, there is
      no integrated approach to identifying secondary causes of both entities. We
      report a cost-effective approach to identify metabolic causes of falls and
      fractures in the clinical setting. PURPOSE: Falls and fractures are a major cause
      of morbidity and mortality among older adults. Metabolic disorders contributing
      to the combined risk of falls and fractures are frequent but often go undetected.
      The most efficient and cost-effective laboratory screening strategy to unmask
      these disorders remains unknown. The purpose of this study was to identify the
      most cost-effective laboratory tests to detect undiagnosed metabolic contributors
      and to decide treatment of these disorders in older persons. METHODS: This is a
      cross-sectional study design, which included all participants attending the Falls
      & Fractures Clinic, Nepean Hospital (Penrith, Australia) between 2008 and 2013.
      Chemistry profile included 25(OH) vitamin D, parathyroid hormone (PTH), albumin,
      creatinine, calcium, phosphate, vitamin B-12, folate, and thyroid-stimulating
      hormone (TSH) for all patients, and serum testosterone in men. The number of new
      diagnoses identified and their cost-effectiveness (cost in US$ per patient
      screened and cost per new diagnosis) were calculated. RESULTS: A total of 739
      participants (mean age 79, 71 % female) were assessed. Among 233 participants
      with complete laboratory tests, previously undiagnosed disorders were identified
      in 148 (63.5 %). Vitamin D deficiency (27 %) and hyperparathyroidism (21.5 %)
      were the most frequent diagnoses. A testing strategy including serum vitamin D,
      calcium, PTH, creatinine/estimated glomerular filtration rate (eGFR), and TSH for
      all patients and serum testosterone in men would have been sufficient to identify
      secondary causes of falls and fractures in 94 % of patients at an estimated cost
      of $190.19 per patient screened and $257.64 per diagnosis. CONCLUSIONS: The
      minimum cost-effective battery for occult metabolic disorders in older adults at
      risk of falls and fractures should include serum vitamin D, PTH, TSH,
      creatinine/eGFR, testosterone (in men), and calcium.

PMID- 26194902
TI  - Computational method for the real-time calculation of the full-body muscle load
      distribution.
AB  - A method is described for minimising a quadratic function subject to equality and
      inequality constraints. This approach is applicable to solving the full-body
      muscle load distribution problem and calculating joint contact loads. It has been
      found that this approach can provide the solution on modest computing facilities
      and in significantly less time than using active set and interior point quadratic
      programming techniques. Hence the approach is suitable for providing real-time
      feedback to subjects undergoing biomechanical analysis of muscle, skeletal and
      joint loadings.

PMID- 26194903
TI  - Amorphous Sb2S3 embedded in graphite: a high-rate, long-life anode material for
      sodium-ion batteries.
AB  - Amorphous Sb2S3 embedded in a conductive graphite matrix is designed for sodium
      ion batteries. Owing to the amorphous structure of the active phase and the
      conductive graphite matrix, the Sb2S3-graphite electrode exhibits a high initial
      Coulomblic efficiency, a high rate capacity, and stable cycle performance in
      sodium-ion batteries. 

PMID- 26194905
TI  - [Severe head trauma by speargun].

PMID- 26194904
TI  - Concise Synthesis of v-Coelenterazines.
AB  - A novel synthetic method for v-coelenterazine (v-CTZ), which is a vinylene
      bridged analog of native CTZ with a large red-shifted luminescence property, is
      described. The synthesis was achieved in a concise way through the use of three
      sequential cross-coupling reactions and ring-closing metathesis (RCM). A newly
      synthesized C2-modified trifluoromethyl analog cf3-v-CTZ showed slightly more red
      shifted luminescence than v-CTZ when it was used as a substrate for Renilla
      luciferases. 

PMID- 26194906
TI  - Thrombolytics for late superior caval vein thrombus in a patient with tricuspid
      atresia and single-lung Glenn anastomosis.
AB  - BACKGROUND: Those with cyanotic heart disease have an elevated bleeding risk but
      also are hypercoaguable. Treating haemodynamically significant thrombi in this
      unique cohort poses a monumental challenge. Case A 29-year-old women with
      tricuspid atresia and left pulmonary artery atresia presented with superior caval
      vein syndrome. She had a right modified Blalock-Taussig shunt as a neonate. A
      left modified Blalock-Taussig shunt performed later failed to establish flow to
      her left lung. At age 5, she had a Fontan procedure to the right lung but could
      not tolerate the physiology and had a low cardiac output syndrome. The Fontan was
      taken down and she was left with a Glenn anastamosis to the right pulmonary
      artery. She did well for years until she had dyspnea, upper extremity oedema and
      "facial fullness". On examination she was tachycardic, hypotensive, and more
      desaturated than baseline. She also had facial plethora. Decision-making
      Echocardiogram showed a large 9 * 3 mm nearly occlusive thrombus in the superior
      caval vein at the bifurcation of the left and right innominate veins. An emergent
      venogram confirmed the location and size of the thrombus. Given the thrombus
      burden and potential for distal embolisation through the Glenn to the single
      functional lung, we chose to treat the patient with thrombolytics. She had
      uncomplicated ICU course and was sent home on warfarin. Follow-up echocardiogram
      showed complete resolution of clot. CONCLUSION: This case shows the importance of
      history and physical exam in caring for this complex cohort of adult patients
      with CHD.

PMID- 26194907
TI  - Recalibrating Rambotti: Disentangling concepts of poverty and inequality.

PMID- 26194908
TI  - [Rivaroxaban versus standard of care in venous thromboembolism prevention
      following hip or knee arthroplasty in daily clinical practice (Spanish data from
      the international study XAMOS)].
AB  - OBJECTIVE: To analyse the effectiveness and safety of rivaroxaban vs. standard
      treatment (ST) in the prevention of venous thromboembolism after hip or knee
      replacement in daily clinical practice in Spain. MATERIAL AND METHOD: A sub
      analysis of the Spanish data in the XAMOS international observational study that
      included patients>18 years who received 10mg o.d. rivaroxaban or ST. FOLLOW-UP:
      up to 3 months after surgery. PRIMARY OUTCOMES: incidence of
      symptomatic/asymptomatic thromboembolic events, bleeding, mortality, and other
      adverse events; SECONDARY OUTCOMES: use of health resources and satisfaction
      after hospital discharge. RESULTS: Of the total 801 patients included, 410
      received rivaroxaban and 391 ST (64.7% heparin, 24.0% fondaparinux, 11%
      dabigatran). The incidence of symptomatic thromboembolic events and major
      bleeding was similar in both groups (0.2% vs. 0.8% wit ST and 0.7% vs. 1.3% with
      ST [EMA criteria]/0.0% vs. 0.3% with ST [RECORD criteria]). The adverse events
      incidence associated with the drug was significantly higher rivaroxaban (overall:
      4.4% vs. 0.8% with ST, P=.001; serious: 1.5% vs. 0.0% with ST, P=.03). The
      rivaroxaban used less health resources after discharge, and the majority
      considered the tolerability as "very good" and the treatment as "very
      comfortable". DISCUSSION: Rivaroxaban is at least as effective as ST in the
      prevention of venous thromboembolism prevention in daily clinical practice, with
      a similar incidence of haemorrhages. It provides greater satisfaction/comfort,
      and less health resources after discharge. These results should be interpreted
      taking into account the limitations inherent in observational studies.

PMID- 26194909
TI  - Anesthetic management of pediatric patients with Sturge-Weber syndrome: our
      experience and a review of the literature.
AB  - INTRODUCTION: Sturge-Weber syndrome (SWS) is a rare sporadic congenital
      neurocutaneous syndrome which is characterized by vascular malformation involving
      the brain, face and eye. The anesthetic management is complicated by its
      localized as well as systemic manifestations, associated anomalies and difficult
      airway due to the presence of angiomas of the oral cavity and airway. We
      retrospective analyzed the perioperative anesthetic management of children with
      SWS undergoing ophthalmic surgery and reviewed the literature. METHODS: Medical
      records and anesthetic charts of all the children with SWS who had undergone an
      ophthalmic procedure under general anesthesia during the past 6 years were
      reviewed. Information related to the demographic profile, preoperative
      evaluation, anesthetic techniques, and perioperative complications were collected
      and analyzed. RESULTS: Forty children with SWS received general anesthesia for an
      ophthalmic procedure within the 6-year period. The median age of the children was
      3 years. 30 (92.5%) children had facial port-wine staining, 10 (25%) had facial
      hypertrophy, 15 (37.5%) had a history of convulsion and 4 (10%) children had
      mental retardation. Inhalational induction was performed in 34 (85%) children
      (sevoflurane 82.8%). A laryngeal mask airway (LMA) and endotracheal tube were
      used in 32 (80%) and 5 (12.5%) cases, respectively. One patient had difficult
      mask ventilation and difficult LMA insertion. There was no significant problem in
      any of the other children. CONCLUSION: Preoperative evaluation with airway
      assessment should be performed with the knowledge of local and systemic
      manifestation of the syndrome. Proconvulsant and anticonvulsant properties of the
      anesthetics, as well as drug interactions of antiepileptic medications should be
      considered when planning anesthesia. Avoiding a rise in intracranial and
      intraocular pressures, vigilant intraoperative monitoring and postoperative care
      are the key for conducting safe anesthesia in these children. For ophthalmic
      procedures, LMAs can be used for airway maintenance with minimal complications in
      children with SWS.

PMID- 26194910
TI  - Mitochondrial roles in disease: a box full of surprises.

PMID- 26194911
TI  - Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease
      mechanisms.
AB  - Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa
      (RDEB)-a severe skin fragility disorder associated with lifelong blistering and
      disabling progressive soft tissue fibrosis. Causative therapies for this complex
      disorder face major hurdles, and clinical implementation remains elusive. Here,
      we report an alternative evidence-based approach to ameliorate fibrosis and
      relieve symptoms in RDEB. Based on the findings that TGF-beta activity is
      elevated in injured RDEB skin, we targeted TGF-beta activity with losartan in a
      preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF
      beta signaling in chronically injured forepaws and halted fibrosis and subsequent
      fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle
      treated RDEB skin uncovered changes in multiple proteins related to tissue
      inflammation. In line with this, losartan reduced inflammation and diminished TNF
      alpha and IL-6 expression in injured forepaws. Collectively, the data argue that
      RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-beta
      mediated inflammation, and matrix remodeling. Inhibition of TGF-beta activity
      limits these unwanted outcomes and thereby substantially ameliorates long-term
      symptoms.

PMID- 26194912
TI  - Mitochondrial diseases caused by toxic compound accumulation: from etiopathology
      to therapeutic approaches.
AB  - Mitochondrial disorders are a group of highly invalidating human conditions for
      which effective treatment is currently unavailable and characterized by faulty
      energy supply due to defective oxidative phosphorylation (OXPHOS). Given the
      complexity of mitochondrial genetics and biochemistry, mitochondrial inherited
      diseases may present with a vast range of symptoms, organ involvement, severity,
      age of onset, and outcome. Despite the wide spectrum of clinical signs and
      biochemical underpinnings of this group of dis-orders, some common traits can be
      identified, based on both pathogenic mechanisms and potential therapeutic
      approaches. Here, we will review two peculiar mitochondrial disorders,
      ethylmalonic encephalopathy (EE) and mitochondrial neurogastrointestinal
      encephalomyopathy (MNGIE), caused by mutations in the ETHE1 and TYMP nuclear
      genes, respectively. ETHE1 encodes for a mitochondrial enzyme involved in sulfide
      detoxification and TYMP for a cytosolic enzyme involved in the
      thymidine/deoxyuridine catabolic pathway. We will discuss these two clinical
      entities as a paradigm of mitochondrial diseases caused by the accumulation of
      compounds normally present in traces, which exerts a toxic and inhibitory effect
      on the OXPHOS system. 

PMID- 26194913
TI  - Semaphorin-3C signals through Neuropilin-1 and PlexinD1 receptors to inhibit
      pathological angiogenesis.
AB  - Retinopathy of prematurity causes visual impairment due to destructive
      neoangiogenesis after degeneration of the retinal microvasculature. This study
      was aimed at analyzing whether local delivery of Semaphorin-3C (Sema3C)
      suppresses pathological retinal angiogenesis. Sema3C exerted potent inhibiting
      effects in cellular models of angiogenesis. In an endothelial cell
      xenotransplantation assay, Sema3C acted primarily on immature microvessels by
      inducing endothelial cell apoptosis. Intravitreal administration of recombinant
      Sema3C disrupted endothelial tip cell formation and cell-cell contacts, which led
      to decreased vascular bed expansion and vessel branching in the growing retinal
      vasculature of newborn mice, while not affecting mature vessels in the adult
      retina. Sema3C administration strongly inhibited the formation of pathological
      pre-retinal vascular tufts during oxygen-induced retinopathy. Mechanistically,
      Sema3C signaled through the receptors Neuropilin-1 and PlexinD1, which were
      strongly expressed on vascular tufts, induced VE-cadherin internalization, and
      abrogated vascular endothelial growth factor (VEGF)-induced activation of the
      kinases AKT, FAK, and p38MAPK. This disrupted endothelial cell junctions, focal
      adhesions, and cytoskeleton assembly resulted in decreased cell migration and
      survival. Thus, this study identified Sema3C as a potent and selective inhibitor
      of pathological retinal angiogenesis. 

PMID- 26194914
TI  - The effect of repeated exposure to ethanol on pre-existing fear memories in rats.
AB  - RATIONALE: There is a high degree of comorbidity between alcohol use disorder and
      post-traumatic stress disorder (PTSD), but little is known about the interactions
      of ethanol with traumatic memories. OBJECTIVES: Using auditory fear conditioning
      in rats, we asked if repeated exposure to ethanol could modify the retrieval of
      fear memories acquired prior to ethanol exposure. METHODS: Following auditory
      fear conditioning, Sprague-Dawley rats were given daily injections of ethanol
      (1.5 g/kg) or saline over 5 days. Two days later, they were given 20 trials of
      extinction training and then tested for extinction memory the following day. In a
      separate experiment, conditioned rats were given repeated ethanol injections and
      processed for c-Fos immunohistochemistry following a fear retrieval session.
      RESULTS: Two days following the cessation of ethanol, the magnitude of
      conditioned fear responses (freezing and suppression of bar pressing) was
      significantly increased. This increase persisted the following day. Waiting 10
      days following cessation of ethanol eliminated the effect on fear retrieval. In
      rats conditioned with low shock levels, repeated exposure to ethanol converted a
      sub-threshold fear memory into a supra-threshold fear memory. It also increased c
      Fos expression in the prelimbic prefrontal cortex, paraventricular thalamus, and
      the central and basolateral nuclei of the amygdala, areas implicated in the
      retrieval of fear memories. CONCLUSIONS: These results suggest that repeated
      exposure to ethanol may exacerbate pre-existing traumatic memories.

PMID- 26194916
TI  - Risk factors for adverse cardiac events in hip fracture patients: an analysis of
      NSQIP data.
AB  - PURPOSE: Cardiovascular complications constitute morbidity and mortality for hip
      fracture patients. Relatively little data exist exploring risk factors for post
      operative complications. Using the American College of Surgeons National Surgical
      Quality Improvement (ACS-NSQIP) database, we identified significant risk factors
      associated with adverse cardiac events in hip fracture patients and provide
      recommendations for practising orthopaedists. METHODS: A cohort of 27,441
      patients with hip fractures from 2006 to 2013 was identified using Current
      Procedural Terminology codes. Cardiac complications were defined as cardiac
      arrests or myocardial infarctions occurring within 30 days after surgery.
      Bivariate analysis was run on over 30 patient and surgical factors to determine
      significant associations with cardiac events. Multivariate logistical analysis
      was then performed to determine risk factors most predictive for cardiac events.
      RESULTS: Of the 27,441 hip fracture patients, 594 (2.2%) had cardiac
      complications within 30 days post-operatively. There was no significant
      association with respect to type of hip fracture surgery and adverse cardiac
      event rates (p = 0.545). After multivariate analysis, dialysis use (OR: 2.22, p =
      0.026), and histories of peripheral vascular disease (OR: 2.11, p = 0.016),
      stroke (OR: 1.83, p = 0.009), COPD (OR: 1.69, p = 0.014), and cardiac disease
      (OR: 1.55, p = 0.017) were significantly predictive of post-operative cardiac
      events in all hip fracture patients. CONCLUSION: Orthopaedic trauma surgeons
      should be aware of cardiac disease history and atherosclerotic conditions (PVD,
      stroke) in risk stratifying patients to prevent cardiac complications. Our
      recommendations to reduce cardiac events include simple pre-operative lab-work to
      full-fledged cardiac work-up and referrals to specific medicine disciplines based
      on the specific risk factors present.

PMID- 26194915
TI  - Comparing the effects of subchronic phencyclidine and medial prefrontal cortex
      dysfunction on cognitive tests relevant to schizophrenia.
AB  - RATIONALE: It is becoming increasingly clear that the development of treatments
      for cognitive symptoms of schizophrenia requires urgent attention, and that valid
      animal models of relevant impairments are required. With subchronic
      psychotomimetic agent phencyclidine (scPCP), a putative model of such impairment,
      the extent to which changes following scPCP do or do not resemble those following
      dysfunction of the prefrontal cortex is of importance. OBJECTIVES: The present
      study carried out a comparison of the most common scPCP dosing regimen with
      excitotoxin-induced medial prefrontal cortex (mPFC) dysfunction in rats, across
      several cognitive tests relevant to schizophrenia. METHODS: ScPCP subjects were
      dosed intraperitoneal with 5 mg/kg PCP or vehicle twice daily for 1 week followed
      by 1 week washout prior to behavioural testing. mPFC dysfunction was induced via
      fibre-sparing excitotoxin infused into the pre-limbic and infralimbic cortex.
      Subjects were tested on spontaneous novel object recognition, touchscreen object
      location paired-associates learning and touchscreen reversal learning. RESULTS: A
      double-dissociation was observed between object-location paired-associates
      learning and object recognition: mPFC dysfunction impaired acquisition of the
      object-location task but not spontaneous novel object recognition, while scPCP
      impaired spontaneous novel object recognition but not object-location associative
      learning. Both scPCP and mPFC dysfunction resulted in a similar facilitation of
      reversal learning. CONCLUSIONS: The pattern of impairment following scPCP raises
      questions around its efficacy as a model of cognitive impairment in
      schizophrenia, particularly if importance is placed on faithfully replicating the
      effects of mPFC dysfunction.

PMID- 26194917
TI  - Section of the anterior cruciate ligament in the rabbit as animal model for
      osteoarthritis progression.
AB  - PURPOSE: The purpose of this study was to determine whether instability of knee
      is a risk factor in the progression of osteoarthritis (OA). METHODS: Twenty-four
      mature New Zealand White rabbits were randomly divided into four groups. The
      control group received 0.3 ml saline in the first, fourth and seventh days in the
      right knee, while the other three groups received the same dosage 4 % papain and
      its activator 0.03 M L-cystein. The P3w group knees were harvested at three weeks
      after the last papain injection, the P6w group knees received a sham surgery at
      three weeks and were harvested at six weeks after the last papain injection,
      while the P+ACLT group knees received ACL transection at three weeks and were
      harvested at six weeks after the last papain injection. Cartilage degradation of
      femoral condyles and tibial plateaus were evaluated by X-rays, macroscopy, light
      microscopic and transmission electron microscopy (TEM). RESULTS: According to X
      rays grade scale, macroscopic grade scale, light microscopic modified Mankin
      scale and TEM, in the P3w knees, cartilage degeneration of femoral condyles and
      tibial plateaus were significantly severe compared to those of the control group
      (P < 0.05), but the differences were not apparent in comparison with the P6w
      knees (P > 0.05). However, in P+ACLT knees, cartilage degeneration of femoral
      condyles and tibial plateaus appeared more severe in comparison with P6w knees,
      and the difference was significant (P < 0.05). CONCLUSIONS: Instability of knee
      plays a significant role in increasing the severity of cartilage degradation in
      rabbit knees and should be considered as a risk factor in OA knee progression.
      Our data may suggest that reconstruction of knee stability may prevent or delay
      the progression of OA.

PMID- 26194918
TI  - Tracheostomy following anterior cervical spine fusion in trauma patients.
AB  - PURPOSE: Traumatic injuries to the cervical spine are frequently accompanied by
      cervical spinal cord injuries-often necessitating tracheostomy. The purpose of
      this study was to evaluate patient characteristics and outcomes after undergoing
      anterior cervical spine fusion (ACSF) with tracheostomy. METHODS: All patients
      with cervical spine injury (CSI) who underwent ACSF and tracheostomy between
      December 1992 and June 2014 were included in this retrospective data analysis.
      The study group consisted of 32 men (84 %) and six women (16 %), with an average
      age of 47 +/- 20 years. Blunt trauma to the cervical spine was the cause of CSI
      in all 38 patients. RESULTS: The mean Injury Severity Score (ISS) was 30.50 +/-
      6.25. Eighteen patients sustained severe concomitant injuries related to the
      spinal injury. In 15 patients (39.5 %), traumatic brain injury (TBI) with
      fractures of the cranium and/or intracranial lesions were observed. The mean
      Glasgow Coma Scale (GCS) score was 11 +/- 4.5 (range 3-15). Two tracheostomies
      (5.3 %) were performed simultaneously with ACSF. The remaining 36 were performed
      with an average "delay" of 15 +/- ten days. We observed no difference in time to
      tracheostomy among patients initially presenting with an American Spinal Injury
      Association (ASIA) score of either A, B, C or D. Only two patients (5.3 %) were
      identified as having an infection at the site of ACSF after placement of a
      tracheostomy. There were no deaths directly related to airway difficulties in our
      cohort. CONCLUSIONS: Our data show that tracheostomy is safely performed after an
      average of 15 days post-ACSF, thereby being associated with a very low rate of
      complications. However, future prospective randomised studies are needed to
      identify the optimal timing of tracheostomy placement after ACSF. LEVEL OF
      EVIDENCE: IV; retrospective case series.

PMID- 26194919
TI  - Clinical and radiographic outcomes of medial open-wedge high tibial osteotomy
      with Anthony-K plate: prospective minimum five year follow-up data.
AB  - PURPOSE: The purpose of this study was to prospectively evaluate the clinical and
      radiographic outcomes, and complication rates, after a minimum of five years of
      follow-up after medial open wedge high tibial osteotomy (MOWHTO) using an Anthony
      K plate. METHODS: MOWHTO was performed on 35 knees of 34 consecutive patients. A
      visual analogue scale (VAS), and Western Ontario and McMaster University
      Osteoarthritis (WOMAC) and Lysholm scores, were used in clinical evaluation. Upon
      radiographic assessment, alignment was expressed as the femorotibial angle (FTA).
      The posterior tibial slope (PTS) and the Insall-Salvati Index (ISI) were also
      measured. RESULTS: VAS, WOMAC, and Lysholm scores improved significantly upon
      follow-up (p < 0.001 for all). The overall mean FTA was 4.68 +/- 4.39 degrees 
      varus pre-operatively; at the last post-operative follow-up, the value was 8.43
      +/- 2.02 degrees  valgus. The mean correction angle was 13.1 +/- 2.7 degrees . A
      significant increase in PTS was evident (p < 0.01), as was a significant decrease
      in the ISI (p < 0.01). The overall complication rate was 8.6 %. CONCLUSIONS: The
      Anthony-K plate affords accurate correction, initially stabilises the osteotomy
      after surgery, and maintains such stability until the osteotomy gap is completely
      healed, without correction loss. The plate survival rate was 97.2 % after a
      minimum of five years of follow-up. The plate increased the PTS, as do other
      medial osteotomy fixation plates.

PMID- 26194920
TI  - Assessing risk factors for in-hospital acute myocardial infarction after total
      joint arthroplasty.

PMID- 26194921
TI  - Transanal total mesorectal excision: a pure NOTES approach for selected patients.
AB  - BACKGROUND: The concept of natural orifice transluminal endoscopic surgery
      (NOTES) has stimulated the development of various "incisionless" procedures. One
      of the most popular is the transanal approach for rectal lesions. The aims of
      this study were to report how we standardized NOTES technique for transanal
      mesorectal excision without abdominal assistance, discuss the difficulties and
      surgical outcomes of this technique and report its feasibility in a small group
      of selected patients. METHODS: Three consecutive female patients underwent
      transanal NOTES rectal resection without transabdominal laparoscopic assistance
      for rectal lesions. Functional results were assessed with the Fecal Incontinence
      Quality of Life scale and the Wexner score. RESULTS: The technical steps are
      described in details and complemented with a video. All procedures were completed
      without transabdominal laparoscopic help. The mesorectal plane was entirely
      dissected without any disruption, and distal and circumferential margins were
      tumor-free. No major complications were observed. Functional results show a
      significant impairment after surgery with improvement at 6 months to levels near
      those of the preoperative period. CONCLUSIONS: The performance and publication of
      NOTES procedures are subject to much discussion. Despite the small number of
      patients, this procedure appears feasible and can be accomplished maintaining
      fecal continence and respecting oncologic principles.

PMID- 26194922
TI  - Alzheimer's disease: a time for cautious optimism.

PMID- 26194923
TI  - Progress towards a neuroimaging biomarker for amyotrophic lateral sclerosis.

PMID- 26194924
TI  - Corrections.

PMID- 26194925
TI  - Corrections.

PMID- 26194926
TI  - William Klunk: imaging Alzheimer's disease in vivo.

PMID- 26194927
TI  - The hinterland of delirium.

PMID- 26194928
TI  - Lifeline.

PMID- 26194929
TI  - UK Government's handling of mad cow disease.

PMID- 26194931
TI  - Pathophysiology, presentation, prognosis, and management of intracranial arterial
      dolichoectasia.
AB  - Up to 12% of patients with stroke have intracranial arterial dolichoectasia
      (IADE) and the basilar artery is affected in 80% of these cases. Diagnostic
      criteria and prognosis studies of IADE are based on basilar artery diameter,
      which is a good quantitative marker for the severity of the disease. The
      pathophysiology is largely unknown, but IADE can be viewed as a common final
      pathway of arterial wall response or damage in the tunica media due to various
      mechanisms, such as matrix metalloproteinase dysfunction or muscle cell or
      elastic fibre injury. No randomised controlled trials have been undertaken in
      IADE and thus little high-level evidence is available on which to base treatment
      guidelines. IADE management depends on clinical presentation and disease
      severity, and includes blood pressure control, antithrombotic treatments,
      endovascular procedures, and surgery. Further studies are needed to better define
      IADE in the general population, to establish its prevalence and pathophysiology,
      to identify subgroups at risk of life-threatening complications, and to offer
      effective treatment options. 

PMID- 26194933
TI  - Automated control of inspired oxygen in ventilated preterm infants: crossover
      physiological study.
AB  - AIM: To evaluate the efficacy of automated control of the fraction of inspired
      oxygen (FiO2 ) in comparison with manual FiO2 control in maintaining target pulse
      oxygen saturation (SpO2 ) range. METHODS: Crossover physiological study involving
      preterm infants requiring mechanical ventilation and supplemental oxygen. Each
      infant was studied for two consecutive 12 hours in a random sequence. Outcome
      measures included the proportion of time with SpO2 within and outside the target
      range of 90-95%, extreme hypoxaemia (< 80%) and hyperoxaemia (>= 98%). RESULTS:
      Complete data set was available in 27 infants. The percentage of time (median,
      IQR) within the target range was higher during automated control 72.8 (58.8-82.6)
      compared to manual control 59.6 (49.3-73.3), p = 0.031. Corresponding reduction
      in per cent time below the target range was 18.1 (12.7-23.6) versus 25.9 (17.8
      30.7), p = 0.028, and above the target range 4.8 (3-16) versus 10.1 (6.4-22.5), p
      = 0.026. Median (IQR) per cent time spent with severe hypoxaemia (SpO2 < 80%) and
      severe hyperoxaemia (SpO2 >= 98%) was 1.3 (0.1-2.9) versus 3.2 (1.4-6.1), p =
      0.022 and 0.08 (0.05-0.36) versus 1.7 (0.7-6.8), p = 0.001, respectively. Median
      number of manual adjustments of FiO2 per 12 hour was 0 and 63, respectively.
      CONCLUSION: Automated control of FiO2 significantly improved compliance of oxygen
      saturation targeting and significantly reduced exposure to hypoxaemia as well as
      hyperoxaemia.

PMID- 26194932
TI  - Runners maintain locomotor-respiratory coupling following isocapnic voluntary
      hyperpnea to task failure.
AB  - INTRODUCTION: Evidence has long suggested that mammalian ventilatory and
      locomotor rhythms are linked, yet determinants and implications of locomotor
      respiratory coupling (LRC) continue to be investigated. Anecdotally, respiratory
      muscle fatigue seen at the end of heavy exercise may result in an uncoupling of
      movement-ventilation rhythms; however, there is no scientific evidence to
      substantiate this claim. PURPOSE: We sought to determine whether or not fatigue
      of the respiratory muscles alters locomotor-respiratory coupling patterns
      typically observed in highly trained individuals while running. A related query
      was to examine the relationship between the potential changes in LRC and measures
      of running economy. METHOD: Twelve male distance runners ran at four submaximal
      workloads (68-89 % VO2peak) on two separate days while LRC was quantified. One
      LRC trial served as a control (CON), while the other was performed following an
      isocapnic voluntary hyperpnea to task failure to induce respiratory muscle
      fatigue (FT+). LRC was assessed as stride-to-breathing frequency ratios (SF/fB)
      and degree of LRC (percentage of breaths occurring during the same decile of the
      step cycle). RESULT: Hyperpnea resulted in significant declines in maximal
      voluntary inspiratory (MIP) and expiratory (MEP) mouth pressures (DeltaMIP = -10
      +/- 12 cm H2O; DeltaMEP = -6 +/- 9 cm H2O). There were no differences in minute
      ventilation between CON and FT+ (CON, all speeds pooled = 104 +/- 25 L min(-1);
      FT+ pooled = 106 +/- 23 L min(-1)). Stride frequency was not different between
      trials; however, breathing frequency was significantly greater during FT+
      compared to CON at all speeds (CON pooled = 47 +/- 10 br min(-1); FT+ pooled = 52
      +/- 9 br min(-1)), resulting in smaller corresponding SF/fB. Yet, the degree of
      LRC was the same during CON and FT+ (CON pooled = 63 +/- 15 %; FT+ pooled = 64 +/
      18 %). CONCLUSION: The results indicate that trained runners are able to
      continue entraining breath and step cycles, despite marked changes in exercise
      breathing frequency, after a fatiguing hyperpnea challenge.

PMID- 26194934
TI  - Application of FISH method for preimplantation genetic diagnostics of reciprocal
      and Robertsonian translocations.
AB  - INTRODUCTION: Carriers of reciprocal (RCP) and Robertsonian (RT) translocations
      are known to be at risk for reproductive difficulties. Preimplantation genetic
      diagnosis (PGD) is one of the options these carriers have to try to fulfill their
      desire to have a child. The FISH technique is one of the best method to detect
      RCPs, and, together with the Next Generation Sequencing, to diagnose RTs. The aim
      of the present study was to assess the usefulness of the FISH method for rapid
      diagnosis of translocations in our center to improve the reproductive counseling.
      MATERIAL AND METHODS: From 2008 to 2012 one hundred and twenty seven fresh cycles
      of the in vitro fertilization (IVF; without freezing embryos) were performed in
      42 couples with an RCP and 35 couples with an RT translocations. The patients
      were diagnosed before IVF as translocation carriers and therefore they opted for
      PGD. The classical FISH protocol has been applied with specific oligonucleotide
      probes. RESULTS: In total 521 blastomeres were tested in order to determine the
      presence or absence of genetic anomalies resulting from one of the parents being
      a translocation carrier. Despite the large number of abnormal embryos (407
      embryos - 78.1% of all examined embryos), 19.4% of blastomeres appeared to come
      from a normal or balanced embryos that may have been transferred to the uterus.
      In 63 of the 127 cycles embryo transfer (ET) was feasible and 24 women had a
      successful singleton or twin pregnancy. Thus, a live delivery rate of 18.9% per
      started cycles and 38.1% per cycle with ET was obtained. CONCLUSION: FISH should
      be regarded as an optimal preimplantation genetic diagnosis method for specific
      RCP and RT translocation carriers to increase the chance of successful IVF
      procedure.

PMID- 26194935
TI  - Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled,
      Randomized, Multicenter Trial.
AB  - STUDY OBJECTIVE: We assess the efficacy and safety of tamsulosin compared with
      placebo as medical expulsive therapy in patients with distal ureteric stones less
      than or equal to 10 mm in diameter. METHODS: This was a randomized, double-blind,
      placebo-controlled, multicenter trial of adult participants with calculus on
      computed tomography (CT). Patients were allocated to 0.4 mg of tamsulosin or
      placebo daily for 28 days. The primary outcomes were stone expulsion on CT at 28
      days and time to stone expulsion. RESULTS: There were 403 patients randomized,
      81.4% were men, and the median age was 46 years. The median stone size was 4.0 mm
      in the tamsulosin group and 3.7 mm in the placebo group. Of 316 patients who
      received CT at 28 days, stone passage occurred in 140 of 161 (87.0%) in the
      tamsulosin group and 127 of 155 (81.9%) with placebo, a difference of 5.0% (95%
      confidence interval -3.0% to 13.0%). In a prespecified subgroup analysis of large
      stones (5 to 10 mm), 30 of 36 (83.3%) tamsulosin participants had stone passage
      compared with 25 of 41 (61.0%) with placebo, a difference of 22.4% (95%
      confidence interval 3.1% to 41.6%) and number needed to treat of 4.5. There was
      no difference in urologic interventions, time to self-reported stone passage,
      pain, or analgesia requirements. Adverse events were generally mild and did not
      differ between groups. CONCLUSION: We found no benefit overall of 0.4 mg of
      tamsulosin daily for patients with distal ureteric calculi less than or equal to
      10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia
      requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did
      increase passage and should be considered.

PMID- 26194936
TI  - A regulatory CD9(+) B-cell subset inhibits HDM-induced allergic airway
      inflammation.
AB  - BACKGROUND: Exposure to respiratory allergens triggers airway hyperresponsiveness
      and inflammation characterized by the expansion of TH 2 cells and the production
      of allergen specific IgE. Allergic asthma is characterized by an alteration in
      immune regulatory mechanisms leading to an imbalance between pro- and anti
      inflammatory components of the immune system. AIMS: Recently B cells have been
      described as central regulators of exacerbated inflammation, notably in the case
      of autoimmunity. However, to what extent these cells can regulate airway
      inflammation and asthma remains to be elucidated. MATERIALS & METHODS: We took
      advantage of a allergic asthma model in mice induced by percutaneous
      sensitization and respiratory challenge with an extract of house dust mite.
      RESULTS: In this study, we showed that the induction of allergic asthma alters
      the homeostasis of IL-10(+) Bregs and favors the production of inflammatory
      cytokines by B cells. Deeper transcriptomic and phenotypic analysis of Bregs
      revealed that they were enriched in a CD9(+) B cell subset. In asthmatic mice the
      adoptive transfer of CD9(+) B cells normalized airway inflammation and lung
      function by inhibiting TH 2- and TH 17-driven inflammation in an IL-10-dependent
      manner, restoring a favorable immunological balance in lung tissues. Indeed we
      further showed that injection of CD9(+) Bregs controls the expansion of lung
      effector T cells allowing the establishment of a favorable regulatory T
      cells/effector T cells ratio in lungs. CONCLUSION: This finding strengthens the
      potential for Breg-targeted therapies in allergic asthma.

PMID- 26194937
TI  - Dynamic NMR study of dinitrophenyl derivatives of seven-membered cyclic ketals of
      pyridoxine.
AB  - Two pyridoxine derivatives containing a dinitrophenyl moiety were investigated by
      (1)H NMR spectroscopy. Conformational dynamics in solution were studied for each
      compound using dynamic NMR experiments. It was shown that both compounds studied
      are involved into two conformational exchange processes. The first process is a
      transformation of the seven-membered cycle conformation between the enantiomeric
      P-twist and M-twist forms, and the second is a rotation of the dinitrophenyl
      fragment of the molecules around the C-O bond. Energy barriers of both
      conformational transitions were determined.

PMID- 26194938
TI  - Age-Related Trends in Hip Arthroscopy: A Large Cross-Sectional Analysis.
AB  - PURPOSE: To analyze a large national private payer population in the United
      States for trends over time in hip arthroscopy by age groups and to determine the
      rate of conversion to total hip arthroplasty (THA) after hip arthroscopy.
      METHODS: We performed a retrospective analysis using the PearlDiver private
      insurance patient record database from 2007 through 2011. Hip arthroscopy
      procedures including newly introduced codes such as osteochondroplasty of cam and
      pincer lesions and labral repair were queried. Hip arthroscopy incidence and
      conversion rates to THA were stratified by age. Chi-squared analysis was used for
      statistical comparison. Conversion to THA was evaluated using Kaplan-Meier
      analysis. RESULTS: From 2007 through 2011, 20,484,172 orthopaedic patients were
      analyzed. Hip arthroscopy was performed in 8,227 cases (mean annual incidence,
      2.7 cases per 10,000 orthopaedic patients). The incidence of hip arthroscopies
      increased over 250% from 1.6 cases per 10,000 in 2007 to 4.0 cases per 10,000 in
      2011 (P < .0001). Patients in the 40 to 49 age group made up 28% of cases,
      followed by patients ages 30 to 39 (22%) and 50 to 59 (19%). Patients under 30
      years old showed the greatest increase in incidence from 2007 to 2011 (335%), but
      patients over 60 still had over a 200% increase. Labral debridement was the most
      common procedure (6,031 cases), and approximately 1.6 procedural codes were
      billed for every case performed. Labral repair was more common in patients under
      30, while labral debridement was more common in older age groups (P = .046).
      Within 24 months of hip arthroscopy, 17% of patients older than 50 required
      conversion to THA, compared with <1% of patients under 30 (P < .0001).
      CONCLUSIONS: Hip arthroscopy procedures are increasing in popularity across all
      age groups, with patients ages 40 to 49 having the highest incidence in this
      large cross-sectional population, despite a high rate of early conversion to THA
      within 2 years in patients over 50. LEVEL OF EVIDENCE: IV, cross-sectional study.

PMID- 26194939
TI  - Surgical Techniques for the Reconstruction of Medial Collateral Ligament and
      Posteromedial Corner Injuries of the Knee: A Systematic Review.
AB  - PURPOSE: To systematically review reconstruction techniques of the medial
      collateral ligament (MCL) and associated medial structures of the knee (e.g.,
      posterior oblique ligament). METHODS: A systematic review of Medline/PubMed
      Database (1966 to November 2013), reference list scanning and citation searches
      of included articles, and manual searches of high-impact journals (2000 to July
      2013) and conference proceedings (2009 to July 2013) were performed to identify
      publications describing MCL reconstruction techniques of the knee. Exclusion
      criteria included (1) MCL primary repair techniques or advancement procedures,
      (2) lack of clear description of MCL reconstruction technique, (3) animal models,
      (4) nonrelevant study design, (5) and foreign language articles without available
      translation. RESULTS: After review of 4,600 references, 25 publications with 359
      of 388 patients (92.5%) were isolated for analysis, including 18 single-bundle
      MCL and 10 double-bundle reconstruction techniques. Only 2 techniques were
      classified as anatomic reconstructions, and clinical and objective outcomes (n =
      28; 100% <3 mm side-to-side difference [SSD]) were superior to those with
      nonanatomic reconstruction (n = 182; 79.1% <3 mm SSD) and tendon transfer
      techniques (n = 114; 52.6% <3 mm SSD). CONCLUSIONS: This systematic review
      demonstrated that numerous medial reconstruction techniques have been used in the
      treatment of isolated and combined medial knee injuries in the existent
      literature. Many variations exist among reconstruction techniques and may differ
      by graft choices, method of fixation, number of bundles, tensioning protocol, and
      degree of anatomic restoration of medial and posteromedial corner knee
      restraints. Further studies are required to better ascertain the comparative
      clinical outcomes with anatomic, non-anatomic, and tendon transfer techniques for
      medial knee reconstruction. LEVEL OF EVIDENCE: Level IV, systematic review of
      level IV studies and surgical techniques.

PMID- 26194942
TI  - Placebo effects and their determinants in gastrointestinal disorders.
AB  - Placebo effects in clinical trials have sparked an interest in the placebo
      phenomenon, both in randomized controlled trials (RCTs) and in experimental
      gastroenterology. RCTs have demonstrated similar short-term and long-term placebo
      response rates in gastrointestinal compared to other medical diagnoses. Most
      mediators and moderators of placebo effects in gastrointestinal diseases are also
      of similar type and size to other medical diagnoses and not specific for
      gastrointestinal diagnoses. Other characteristics such as an increase in the
      placebo response over time and the placebo-enhancing effects of unbalanced
      randomization were not seen, at least in IBS. Experimental placebo and nocebo
      studies underscore the 'power' of expectancies and conditioning processes in
      shaping gastrointestinal symptoms not only at the level of self-reports, but also
      within the brain and along the brain-gut axis. Brain imaging studies have
      redressed earlier criticism that placebo effects might merely reflect a response
      bias. These findings raise hope that sophisticated trials and experiments
      designed to boost positive expectations and minimize negative expectations could
      pave the way for a practical and ethically sound use of placebo knowledge in
      daily practice. Rather than focusing on a 'personalized' choice of drugs based on
      biomarkers or genes, it might be the doctor-patient communication that needs to
      be tailored. 

PMID- 26194945
TI  - Immunology: Gut migration of innate lymphoid cells.

PMID- 26194940
TI  - Eosinophilic Esophagitis: A Comprehensive Review.
AB  - Eosinophilic esophagitis (EoE) is an emerging chronic atopic clinical-pathologic
      disease with an estimated prevalence of 1/1000 similar to the one of Crohn's
      diseases. Usually, EoE is firstly suspected due to symptoms that are caused by
      esophageal dysfunction and/or fibrosis. EoE diagnosis is confirmed if the
      esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf) as
      a peak value in one or more of at least four specimens obtained randomly from the
      esophagus. Most of the patients affected by EoE have other atopic diseases such
      as allergic rhinitis, asthma, IgE-mediated food allergies, and/or atopic
      dermatitis. The local inflammation is a T helper type 2 (Th2) flogosis, which
      most likely is driven by a mixed IgE and non-IgE-mediated reaction to food and/or
      environmental allergens. Recently published genetic studies showed also that EoE
      is associated with single nucleotide polymorphism (SNP) on genes which are
      important in atopic inflammation such as thymic stromal lymphopoietin (TSLP)
      located close to the Th2 cytokine cluster (IL-4, IL-5, IL-13) on chromosome 5q22.
      When the EoE diagnosis is made, it is imperative to control the local
      eosinophilic inflammation not only to give symptomatic relief to the patient but
      also to prevent complications such as esophageal stricture and food impaction.
      EoE is treated like many other atopic diseases with a combination of topical
      steroids and/or food antigen avoidance. 

PMID- 26194946
TI  - Coeliac disease &gluten sensitivity: Epithelial stress enters the dance in
      coeliac disease.

PMID- 26194948
TI  - The promise of metabolic phenotyping in gastroenterology and hepatology.
AB  - Disease risk and treatment response are determined, at the individual level, by a
      complex history of genetic and environmental interactions, including those with
      our endogenous microbiomes. Personalized health care requires a deep
      understanding of patient biology that can now be measured using a range of '
      omics' technologies. Patient stratification involves the identification of
      genetic and/or phenotypic disease subclasses that require different therapeutic
      strategies. Stratified medicine approaches to disease diagnosis, prognosis and
      therapeutic response monitoring herald a new dimension in patient care. Here, we
      explore the potential value of metabolic profiling as applied to unmet clinical
      needs in gastroenterology and hepatology. We describe potential applications in a
      number of diseases, with emphasis on large-scale population studies as well as
      metabolic profiling on the individual level, using spectrometric and imaging
      technologies that will leverage the discovery of mechanistic information and
      deliver novel health care solutions to improve clinical pathway management. 

PMID- 26194949
TI  - Morphology and Physicochemical Properties of 3 Lilium Bulb Starches.
AB  - Lilium (Liliaceae) is an important wild plant and is used as food and traditional
      medicine worldwide. One Lilium cultivar (Lilium lancifolium) and 2 wild types
      (Lilium leucanthum and Lilium rosthornii) that are commonly distributed in
      Western China were investigated to completely utilize Lilium resources. The
      morphology of the flowers, bulbs, and scales and soluble sugar, total starch and
      amylose contents was remarkably different among the 3 Lilium species. Starches
      from the 3 Lilium species presented different granule size and shape. The starch
      of L. lancifolium exhibited higher swelling power and solubility than that of L.
      leucanthum and L. rosthornii. The starches from the 3 Lilium bulbs presented
      similar X-ray diffraction patterns and Fourier transform infrared spectroscopy.
      Among the 3 Lilium species, L. lancifolium showed the lowest crystallinity and
      the largest proportion of ordered structures in granule external region.
      Gelatinization temperatures and retrogradation percentage were significantly
      lower, but gelatinization enthalpy was significantly higher in L. lancifolium
      than those in L. leucanthum and L. rosthornii. Pasting properties of starch were
      different among the 3 Lilium species. Starch from L. lancifolium showed the
      highest degree of amylopectin branching, followed by L. leucanthum and L.
      rosthornii. Starches from L. leucanthum and L. rosthornii showed higher
      resistance to porcine pancreatic alpha-amylase hydrolysis compared to that of L.
      lancifolium. These results indicated that 3 Lilium bulbs exhibited remarkable
      differences in morphological, crystal, thermal, pasting, and hydrolysis
      properties of starches. 

PMID- 26194950
TI  - Prediction of Intraoperative Circulatory Risk Based on Preoperative Neutrophil-to
      Lymphocyte Ratio in Patients Undergoing Living Donor Liver Transplantation.
AB  - BACKGROUND: Intraoperative circulatory risk factors are associated with
      unfavorable outcomes after living donor liver transplantation (LDLT). We
      investigated whether the preoperative neutrophil-to-lymphocyte ratio (NLR) can
      predict intraoperative circulatory risks. MATERIAL AND METHODS: The perioperative
      data of 276 patients who underwent LDLT were reviewed retrospectively. The
      intraoperative circulatory risk score (ICRS) was calculated using the inotropic
      score, hypotension, blood transfusion, oliguria, and change in serum lactate
      during LDLT. Perioperative variables including NLRs were compared between the
      high (>=3.0) and low (<3.0) ICRS groups, and a predictive model for high ICRS was
      developed. RESULTS: A high ICRS was associated with poor preoperative physical
      condition and unfavorable postoperative outcomes. The NLR progressively increased
      during the LDLT perioperative period. However, only preoperative NLRs differed
      significantly between the high and low ICRS groups (6.2 vs. 3.9, respectively;
      p<0.05). The predictive accuracy of the NLR (area under the receiver operator
      curve, 0.635) did not differ from those of the model for end-stage liver disease
      (MELD) and Child-Pugh-Turcotte scores. After multivariate adjustment,
      preoperative NLR >=3.8 was identified as an independent predictor of high ICRS
      (risk ratio 3.15; p=0.004) together with preoperative hemodialysis and
      intraoperatively administered calcium chloride. CONCLUSIONS: Intraoperative
      circulatory risks are associated with several detrimental outcomes following
      LDLT. The preoperative NLR is predictive of intraoperative circulatory risks.

PMID- 26194951
TI  - Diagnostic role of an oligonucleotide array in a heart transplantation patient
      with invasive pulmonary aspergillosis.

PMID- 26194952
TI  - Molecular characterization of extended-spectrum beta-lactamase-producing
      Escherichia coli and Klebsiella spp. isolates in Mongolia.
AB  - BACKGROUND/PURPOSE: The aim of this study was to determine the molecular
      characteristics of beta-lactamase genes in extended-spectrum beta-lactamase
      (ESBL)-producing Enterobacteriaceae isolates from Mongolia. METHODS: Fifty-six
      ESBL-producing Enterobacteriaceae isolates were collected, of which 46 were
      Escherichia coli, seven were Klebsiella pneumoniae, and three were K. oxytoca.
      Minimum inhibitory concentrations for selected antibiotics were tested using the
      agar dilution method, and the beta-lactamase genes were determined using
      polymerase chain reaction combined with sequencing. Pulsed-field gel
      electrophoresis (PFGE) was used for genotyping all isolates, and phylogenetic
      grouping was performed on ESBL-producing E. coli isolates. Conjugation tests
      combined with plasmid digestion assays were used to determine whether there was a
      horizontal spread in Mongolia. RESULTS: Among the 56 ESBL-producing isolates, 43
      isolates (76.8%) were resistant to fluoroquinolones, but all isolates were
      susceptible to carbapenems and amikacin. The polymerase chain reaction sequencing
      results showed that the dominant CTX-M genotype was CTX-M-15 (19/46, 41.3%) in
      the ESBL-producing E. coli isolates. By contrast, CTX-M-14 and CTX-M-3 were the
      major genotypes found in Klebsiella spp. Phylogenetic analysis revealed that 21
      ESBL-producing E. coli isolates belonged to group D (21/46, 45.6%), followed by
      group A (13/46, 28.3%), group B2 (11/46, 23.9%), and group B1 (1/46, 2.2%). Only
      four E. coli isolates (4/46, 8.7%) belonged to the ST131 clone. PFGE showed that
      the ESBL-producing Enterobacteriaceae were genetically unrelated. The conjugation
      assay showed that two plasmids harboring CTX-M-15 in E. coli isolates were
      genetic unrelated, whereas seven plasmids harboring CTX-M-14 (5/7 and 2/7) and
      four plasmids harboring CTX-M-55 (4/4) showed genetic relatedness, indicating the
      dissemination of resistance plasmids in this area.

PMID- 26194953
TI  - Remodeling of extracellular matrix due to solid stress accumulation during tumor
      growth.
AB  - Solid stresses emerge as the expanding tumor displaces and deforms the
      surrounding normal tissue, and also as a result of intratumoral component
      interplay. Among other things, solid stresses are known to induce extensive
      extracellular matrix synthesis and reorganization. In this study, we developed a
      mathematical model of tumor growth that distinguishes the contribution to stress
      generation by collagenous and non-collagenous tumor structural components, and
      also investigates collagen fiber remodeling exclusively due to solid stress. To
      this end, we initially conducted in vivo experiments using an orthotopic mouse
      model for breast cancer to monitor primary tumor growth and derive the mechanical
      properties of the tumor. Subsequently, we fitted the mathematical model to
      experimental data to determine values of the model parameters. According to the
      model, intratumoral solid stress is compressive, whereas extratumoral stress in
      the tumor vicinity is compressive in the radial direction and tensile in the
      periphery. Furthermore, collagen fibers engaged in stress generation only in the
      peritumoral region, and not in the interior where they were slackened due to the
      compressive stress state. Peritumoral fibers were driven away from the radial
      direction, tended to realign tangent to the tumor-host interface, and were also
      significantly stretched by tensile circumferential stresses. By means of this
      remodeling, the model predicts that the tumor is enveloped by a progressively
      thickening capsule of collagen fibers. This prediction is consistent with long
      standing observations of tumor encapsulation and histologic sections that we
      performed, and it further corroborates the expansive growth hypothesis for the
      capsule formation. 

PMID- 26194954
TI  - Convergent evolution of highly reduced fruiting bodies in Pezizomycotina suggests
      key adaptations to the bee habitat.
AB  - BACKGROUND: Among the understudied fungi found in nature are those living in
      close association with social and solitary bees. The bee-specialist genera
      Bettsia, Ascosphaera and Eremascus are remarkable not only for their specialized
      niche but also for their simple fruiting bodies or ascocarps, which are
      morphologically anomalous in Pezizomycotina. Bettsia and Ascosphaera are
      characterized by a unicellular cyst-like cleistothecium known as a spore cyst,
      while Eremascus is characterized by completely naked asci, or asci not formed
      within a protective ascocarp. Before molecular phylogenetics the placement of
      these genera within Pezizomycotina remained tentative; morphological characters
      were misleading because they do not produce multicellular ascocarps, a defining
      character of Pezizomycotina. Because of their unique fruiting bodies, the close
      relationship of these bee-specialist fungi and their monophyly appeared certain.
      However, recent molecular studies have shown that Bettsia is not closely related
      to Ascosphaera. In this study, I isolated the very rare fungus Eremascus fertilis
      (Ascomycota, Pezizomycotina) from the bee bread of honey bees. These isolates
      represent the second report of E. fertilis both in nature and in the honey bee
      hive. To establish the systematic position of E. fertilis and Bettsia alvei, I
      performed phylogenetic analyses of nuclear ribosomal LSU + SSU DNA sequences from
      these species and 63 additional ascomycetes. RESULTS: The phylogenetic analyses
      revealed that Eremascus is not monophyletic. Eremascus albus is closely related
      to Ascosphaera in Eurotiomycetes while E. fertilis belongs in Myxotrichaceae, a
      putative member of Leotiomycetes. Bettsia is not closely related to Ascosphaera
      and like E. fertilis apparently belongs in Leotiomycetes. These results indicate
      that both the naked ascus and spore cyst evolved twice in the Pezizomycotina and
      in distantly related lineages. The new genus Skoua is described to accommodate E.
      fertilis. CONCLUSIONS: The naked ascus and spore cyst are both shown to have
      evolved convergently within the bee habitat. The convergent evolution of these
      unusual ascocarps is hypothesized to be adaptive for bee-mediated dispersal.
      Elucidating the dispersal strategies of these fungal symbionts contributes to our
      understanding of their interaction with bees and provides insight into the
      factors which potentially drive the evolution of reduced ascocarps in
      Pezizomycotina.

PMID- 26194956
TI  - The Innovation Paradox.

PMID- 26194955
TI  - ADAPTA: A pilot randomised controlled trial of an alcohol-focused intervention
      versus a healthy living intervention for problem drinkers identified in a general
      hospital setting.
AB  - AIM: To examine the relative feasibility, acceptability, applicability,
      effectiveness and explore cost-effectiveness of a healthy living focused
      intervention (HL) compared to an alcohol-focused intervention (AF) for problem
      drinkers identified in hospital. METHODS: A pragmatic, randomised, controlled,
      open pilot trial. Feasibility and acceptability were measured by recruitment,
      attrition, follow-up rates and number of treatment sessions attended.
      Effectiveness was measured using the Alcohol Use Disorders Identification Test
      score at six months. Additional economic and secondary outcome measures were
      collected. RESULTS: Eighty-six participants were randomised and 72% (n=62) were
      retained in full participation. Forty-one participants attended at least one
      treatment session (48%). A greater proportion in the HL group attended all four
      treatment sessions (33% vs 19%). Follow-up rates were 29% at six months and 22%
      at twelve months. There was no evidence of a difference in AUDIT score between
      treatment groups at six months. Mean cost of health care and social services,
      policing and the criminal justice system use decreased while EQ-5D scores
      indicated minor improvement in both arms. However, this pilot trial was not
      powered to detect differences in either measure between groups. CONCLUSIONS:
      While no treatment effect was observed, this study demonstrated a potential to
      engage patients drinking at harmful or dependent levels in a healthy living
      intervention. However, recruitment proved challenging and follow-up rates were
      poor. Better ways need to be found to help these patients recognise the harms
      associated with their drinking and overcome the evident barriers to their
      engagement with specialist treatment.

PMID- 26194957
TI  - Perceptions of the Role of the Doctor of Nursing Practice-Prepared Nurse: Clarity
      or Confusion.
AB  - Confusion and disagreement about the DNP degree and its implications continues
      despite the rapid and steady growth of DNP programs. There is a paucity of
      literature that examines nurses' perceptions of the role of the DNP-prepared
      nurse. The purpose of this study was to explore how nurses perceive the role of
      the DNP-prepared nurse and identify areas of ambiguity in understanding the roles
      that DNP-prepared nurses fulfill. A descriptive, cross-sectional design, using
      self-administered questionnaires, explored the perceptions of n = 340 nurses with
      various educational levels and backgrounds. Descriptives of the sample and
      instruments were conducted as well as chi-square analyses to detect differences
      in perceptions across levels of education. Results indicated that nurses clearly
      supported the DNP degree with a focus on the improvement of health care outcomes
      through the roles of leadership in health organizations, policy,
      interprofessionalism, and translation of evidence into practice. Multiple areas
      of confusion concerning the role of DNP-prepared nurse existed in academia,
      academia leadership, and scholarship. In order to reduce role ambiguity, the
      distinctive contributions of the DNP-prepared nurse must be embraced, valued, and
      operationalized. Otherwise, the role of the DNP-prepared nurse will continue to
      be discussed, debated, and challenged. 

PMID- 26194958
TI  - Beyond Academic Evidence: Innovative Uses of Technology Within e-Portfolios in a
      Doctor of Nursing Practice Program.
AB  - Portfolios have been used in higher education for the past several years for
      assessment of student learning and growth and serve as the basis for summative
      and formative evaluations. While there is some information in the literature on
      how undergraduate and graduate medical, nursing, and allied health students might
      use portfolios to showcase acquired knowledge and skills, there is a dearth of
      information on the use of e-Portfolios with students in doctor of nursing
      practice programs. There are also limited findings regarding the creative use of
      technology (that includes infographics and other multimedia tools) to enhance
      learning outcomes (Stephens & Parr, 2013). This article presents engaging and
      meaningful ways technology can be used within e-Portfolios. Thus, e-Portfolios
      become more than a repository for academic evidence; they become unique stories
      that reflect the breadth and depth of students' learner-centered outcomes. 

PMID- 26194959
TI  - Sense Making and Knowledge Transfer: Capturing the Knowledge and Wisdom of
      Nursing Leaders.
AB  - Experienced nurse leaders possess leadership wisdom that must be passed on in
      thoughtful, systematic ways to younger leaders. Sense making is an intentional
      process that has been useful in bringing forward a leader's implicit knowledge
      and wisdom gained over the years. This article examines leadership wisdom,
      complexity, and knowledge in the context of today's dynamic environment-and
      offers a concrete example of how the sense-making methodology can work. 

PMID- 26194960
TI  - Academic Leadership Development: A Case Study.
AB  - A dean at a private school of nursing implemented a leadership development
      program for early- to mid-career nursing faculty consisting of one 4-hour evening
      session per academic quarter for 7 quarters. Eight faculty members who had
      expressed interest in assuming a leadership role or been recommended by their
      supervisors as having strong leadership potential were invited to join. Program
      topics included leadership pathways, legal issues, budgeting and governance,
      diversity, the political arena, human resources, and student issues. Interviews
      with participants revealed 6 themes: the support a peer cohort provided, a desire
      for real-life application, a lack of previous exposure to related content or
      experiences, new perceptions of themselves as academic nurse leaders, the value
      of the program as preparation for academic nursing leadership roles, and broad
      program applicability. 

PMID- 26194961
TI  - Systematic Preparation for Teaching in a Nursing Doctor of Philosophy Program.
AB  - Lack of preparation for the faculty role, particularly for teaching, has long
      been an area of concern in graduate nursing education. This article describes a
      systematic approach to preparing students in a doctor of philosophy (PhD) program
      for their future roles as nurse educators. All PhD students at Rush University
      are required to take a nursing education course that contains four modules: the
      teacher, learner, and learning environment; the basics of curriculum and course
      design; evaluation of the learner, course, program, and institution; and the new
      faculty member. Students also complete a practicum in the course. Students are
      interviewed before the course begins and complete a self-assessment of their
      teaching experiences. Based on their learning needs, students are enrolled in the
      course for variable credit. The course has received excellent evaluations since
      its inception. The success of this course demonstrates that an education course
      can be an essential component of the nursing PhD curriculum. 

PMID- 26194962
TI  - Capacity of, and Demand for, Pediatric Nurse Practitioner Educational Programs: A
      Missing Piece of the Workforce Puzzle.
AB  - BACKGROUND: In contrast to family nurse practitioners and other adult nurse
      practitioners, the percentage of new pediatric nurse practitioners (PNPs)
      graduating each year has not increased. PURPOSE: The aim of this study was to
      determine whether the marginal increase in the pipeline for PNPs is related to a
      limit in the capacity of educational programs or whether unfilled student
      openings exist. METHODS: Self-administered survey of program directors at all
      recognized PNP educational programs in the United States. RESULTS: Approximately
      10% of PNP programs in the United States were either closed, put on hold, or did
      not have new graduates in the last 3 years. Even with these closures, over 25% of
      active programs did not fill all available positions for the class entering in
      2012. CONCLUSION: Despite evidence that demonstrates plans by employers to hire a
      greater number of PNPs in a variety of clinical venues including pediatric
      hospitals, primary care and subspecialty pediatric practices, the PNP pipeline
      has remained relatively stagnant. More than one third of program directors do not
      believe that their PNP program is currently at capacity, indicating that
      underutilized capacity to educate PNPs is a hindrance to meeting the current and
      future demands for these professionals.

PMID- 26194963
TI  - Capacity of, and Demand for, Neonatal Nurse Practitioner Educational Programs: A
      Missing Piece of the Workforce Puzzle.
AB  - BACKGROUND: Studies have demonstrated a dramatic increase in the number of new
      nurse practitioners (NPs) overall completing NP education each year. However, NPs
      who provide specialized care to children have not experienced increases in their
      pipeline at all. This has resulted in shortages of neonatal nurse practitioners
      (NNPs). PURPOSE: The aim of this study was to gain a greater understanding of the
      NNP pipeline and potential for increasing the number of new NNPs graduating each
      year. METHODS: Telephone survey of all NNP educational programs. DISCUSSION:
      Approximately one fourth of all NNP education programs had closed over the past
      several years. This is despite a strong job market, planned increases in hiring
      NNPs, and a seemingly growing shortage of NNPs. CONCLUSION: Problems with the NNP
      pipeline are not due to a lack of capacity of existing programs, but rather to
      difficulties in increasing the enrollment demand.

PMID- 26194964
TI  - "Never in All My Years... ": Nurses' Education About LGBT Health.
AB  - In spite of recent calls for patient-centered care and greater attention to the
      needs of lesbian, gay, bisexual, and transgender (LGBT) patients, nurses still
      lack basic education about LGBT patient care and, as a result, may have negative
      attitudes, endorse stereotypes, and/or feel uncomfortable providing care. This
      study reports on education/training of practicing nurses and explores some of the
      reasons for nurses reporting feelings of discomfort with LGBT patient care.
      Transcripts from structured interviews with 268 nurses in the San Francisco Bay
      Area revealed that 80% had no education or training on LGBT issues. Although most
      said they were comfortable with LGBT patient care, some of their comments
      indicated that they might not be providing culturally sensitive care.
      Implications for nursing education and for policies and procedures of health care
      institutions are addressed. 

PMID- 26194965
TI  - Changes in Perceptions and Attitudes of Healthcare Profession Students Pre and
      Post Academic Course Experience of Team-Based 'Care for the Critically Ill'.
AB  - The aim of this study was to describe the development and outcomes of an
      interprofessional course "Interprofessional Care of the Critically Ill,"
      involving pharmacy, nursing, social work, and respiratory therapy students from
      two universities. An institutional review board-approved survey was adapted from
      the TeamSTEPPS surveys investigating clinical practitioners' attitudes and
      perceptions regarding teamwork, collaboration, and interprofessional engagement.
      Items applicable to an academic setting were revised and resulted in a 28
      statement survey and comments section. Participation was voluntary, and students
      were requested to participate in the survey on the first and last day of class.
      There was a significant increase in the perceived understanding of scope of
      practice of other disciplines from the beginning to end of class (24.4 to 60%,
      strongly agreed/agreed). Furthermore, students gained appreciation for the
      complexities associated with working in an interprofessional team with a
      significant increase in the percent agreeing and strongly agreeing that working
      on an interdisciplinary team is challenging (66.7 to 81%). Students and faculty
      gained a greater understanding and appreciation for other disciplines represented
      in the class and are therefore better prepared to engage in health care teams
      upon graduation. IPE should be embedded in curriculums and not just an add-on. 

PMID- 26194966
TI  - Evidence-Guided Integration of Interprofessional Collaborative Practice into
      Nurse Managed Health Centers.
AB  - The Division of Nursing, Bureau of Health Workforce, has spearheaded a 3-year
      effort to increase the skills of nurses to lead interprofessional collaborative
      practice (IPCP) teams. Since 2012, the Nurse Education, Practice, Quality and
      Retention program has funded 53 sites engaged in this work. The purposes of this
      report are to describe the IPCP framework undergirding implementation at one such
      site, describe the evaluation components and approach, describe how health
      professions students are integrated into this model, and discuss implications of
      IPCP for future nurse-managed/nurse-led initiatives within an evolving health
      care environment. Core team members include a family nurse practitioner,
      physician, pharmacist, social worker, and community health advocate. The clinic
      is located within a public housing complex; the target population is largely
      uninsured or underinsured with a historically high rate of emergency department
      utilization. 

PMID- 26194967
TI  - Academic-Practice Partnerships for Unemployed New Graduates in California.
AB  - In California, academic-practice partnerships offer innovative transition
      programs to new registered nurse (RN) graduates who have not yet found positions
      in nursing. This report describes the formation of 4 partnerships between 1 or
      more schools of nursing and clinical practice sites that included hospitals and
      nonacute care settings, such as hospice, clinics, school districts, and skilled
      nursing facilities. Factors facilitating the partnerships included relationships
      established as nurse leaders from practice and academia came together to address
      previous workforce issues, positive interpersonal experiences, an independent
      convening and coordinating organization, a shared understanding of the employment
      challenge faced by new RN graduates, and a shared vision for its solution.
      Partnerships face continuing challenges that include sustaining engagement,
      resource constraints, and insufficient nursing leadership succession planning.
      Partnership benefits include improved relationships between academia and
      practice, a forum to address contemporary issues in nursing education and
      practice advances, and stimulation of a reassessment of how to integrate
      ambulatory, transitional, and community-based nursing into prelicensure
      education. 

PMID- 26194968
TI  - Linking Learners for Life Where They Live (L4): Developing a Global Health
      Initiative for Student Engagement.
AB  - This article describes a graduate student learning experience as part of an
      international nursing collaborative working together to develop an academic
      partnership for global health education in the circumpolar north. The experience
      provided an opportunity to conduct a pilot project in a rural, remote, northern
      community using an indigenous, global context. Building on the Canadian-Siberian
      collaboration, the graduate student attended an academic institution in Siberia,
      where she focused on the sharing of expertise, knowledge, and insights in order
      to address the challenges facing indigenous people in achieving optimal health
      and well-being in the circumpolar north. The goal was to create a foundation for
      "putting health into place" in a northern context, with the hope of creating
      shared learning opportunities for undergraduate students between the 2
      countries.The intent is to share the approach used by the graduate student to use
      a conceptual model to assess the feasibility of creating a context-relevant
      global health experience for northern nursing education. 

PMID- 26194969
TI  - Lack of Preparation: Iranian Nurses' Experiences During Transition From College
      to Clinical Practice.
AB  - Graduate nurse transition from college to professional practice is an important
      matter in a nurse's professional life. In many cases, this period is
      characterized by unhealthy physical and mental reactions, loss of interest in
      one's profession, and unacceptable caregiving. By examining the phenomenon from
      the point of view of experienced nurses, we can recognize the major factors in a
      successful transition from college life to professional life. This is a
      qualitative study and was conducted based on conventional qualitative content
      analysis method; 14 nurses were selected through purposive sampling, and the data
      were collected using semistructured interviews in teaching hospitals in Iran.
      Eight subthemes emerged from the analysis of the interviews: lack of practical
      skills, limited academic knowledge, inadequate social skills, poor self
      confidence, lack of independence, frustration, stress, and loneliness. These
      items, in turn, fall under 3 themes: poor efficiency, low self-assurance, and
      unhealthy emotional reactions. The findings of this study indicate that the
      participants were not well prepared to assume their clinical roles, which in turn
      gives rise to other problems; to eliminate this defect, the curriculum needs to
      be revised, proper training programs should accompany the students' studies, and
      management in clinical environments recommended should be improved in order to
      facilitate nurses' transition from college to practice. 

PMID- 26194970
TI  - Retzius-sparing robot-assisted laparoscopic radical prostatectomy: Critical
      appraisal of the anatomic landmarks for a complete intrafascial approach.
AB  - To provide an overview of the anatomical landmarks needed to guide a retropubic
      (Retzius)-sparing robot-assisted laparoscopic prostatectomy (RALP), and a step-by
      step description of the surgical technique that maximizes preservation of the
      periprostatic neural network. The anatomy of the pelvic fossae is presented,
      including the recto-vesical pouch (pouch of Douglas) created by the reflections
      of the peritoneum. The actual technique of the trans-Douglas, intrafascial nerve
      sparing robotic radical prostatectomy is described. The technique allows the
      prostate gland to be shelled out from under the overlying detrusor apron and
      dorsal vascular complex (DVC-Santorini plexus), entirely avoiding the pubovesical
      ligaments. There is no need to control the DVC, since the line of dissection
      passes beneath the plexus. Three key points to ensure enhanced nerve preservation
      should be respected: (1) the tips of the seminal vesicles, enclosed in a "cage"
      of neuronal tissue; a seminal vesicle-sparing technique is therefore advised when
      oncologically safe; (2) the external prostate-vesicular angle; (3) the lateral
      surface of the prostate gland and the apex. The principles of tension and energy
      free dissection should guide all the maneuvers in order to minimize neuropathy.
      Using robotic technology, a complete intrafascial dissection of the prostate
      gland can be achieved through the Douglas space, reducing surgical trauma and
      providing excellent functional and oncological outcomes.

PMID- 26194971
TI  - Infidelity in Dating Relationships: Gender-Specific Correlates of Face-to-Face
      and Online Extradyadic Involvement.
AB  - This study examined the gender-specific correlates of face-to-face and online
      extradyadic involvement (EDI) in dating relationships. The sample consisted of
      561 women (M age = 23.19 years) and 222 men (M age = 23.97 years), all of whom
      reported being in an exclusive dating relationship for an average of 35 months.
      Participants completed the following self-report measures: Extradyadic Behavior
      Inventory, Attitudes toward Infidelity Scale, and Investment Model Scale. During
      the current relationship, men were more likely than women to report engagement in
      face-to-face physical/sexual EDI (23.4 vs. 15.5 %) and online sexual EDI (15.3
      vs. 4.6 %). Both men and women with a history of infidelity in a prior
      relationship were more likely to engage in EDI. More positive attitudes toward
      infidelity, lower relationship satisfaction, lower commitment, and higher quality
      of alternatives were significantly associated with EDI, regardless of gender.
      Women reporting infidelity of a partner in a prior relationship were more likely
      to engage in face-to-face and online emotional EDI; a longer relationship and a
      younger age at the first sexual encounter were significant correlates of the
      engagement in face-to-face emotional EDI. Women with higher education were
      approximately three times more likely to engage in online sexual EDI. Although
      men and women are converging in terms of overall EDI, men still report higher
      engagement in physical/sexual extradyadic behaviors, and the correlates of sexual
      and emotional EDI vary according to gender. This study contributes to a
      comprehensive approach of factors influencing the likelihood of EDI and
      encourages future research in this area. 

PMID- 26194972
TI  - Common dependence on stress for the statistics of granular avalanches and
      earthquakes.
AB  - Both earthquake size-distributions and aftershock decay rates obey power laws.
      Recent studies have demonstrated the sensibility of their parameters to faulting
      properties such as focal mechanism, rupture speed or fault complexity. The
      faulting style dependence may be related to the magnitude of the differential
      stress, but no model so far has been able to reproduce this behaviour. Here we
      investigate the statistical properties of avalanches in a dissipative, bimodal
      particulate system under slow shear. We find that the event size-distribution
      obeys a power law only in the proximity of a critical volume fraction, whereas
      power-law aftershock decay rates are observed at all volume fractions accessible
      in the model. Then, we show that both the exponent of the event size-distribution
      and the time delay before the onset of the power-law aftershock decay rate are
      decreasing functions of the shear stress. These results are consistent with
      recent seismological observations of earthquake size-distribution and aftershock
      statistics. 

PMID- 26194973
TI  - Sexual protective strategies and condom use in middle-aged African American
      women: a qualitative study.
AB  - The heterosexual transmission of HIV has affected middle-aged African American
      women at alarming rates; yet there is a paucity of research and interventions
      focused on this population. This study used a qualitative approach to understand
      middle-aged urban African American women's experiences with HIV-related sexual
      risk behaviors and to identify the sexual protective strategies they employed to
      reduce their risk for HIV infection. Ten African American women, ages 45 to 56
      years, were recruited from low-income neighborhoods in New York City. Data were
      collected using in-depth interviews and analyzed using content analysis.
      Investigator triangulation and member checking were used to ensure rigor. Five
      salient themes emerged that highlighted the individual, gender/relationship power
      factors, and the sociocultural elements that influenced sexual protection or risk
      taking behavior. Findings provide new insight into the complexities of HIV sexual
      risk behavior and can guide future HIV prevention interventions for middle-aged,
      African American, urban women. 

PMID- 26194974
TI  - Emergence of antimicrobial-resistant uropathogens isolated from pediatric
      patients with cystitis on daily clean intermittent catheterization.
AB  - One of the major complications of clean intermittent catheterization (CIC) is
      urinary tract infection (UTI). Recent reports showed that community-acquired UTIs
      caused by antimicrobial-resistant pathogens were gradually presenting in adults.
      However, there have been few reports about UTIs caused by antimicrobial-resistant
      bacteria in pediatric patients. Therefore, we retrospectively reviewed the
      medical charts of 45 children with CIC due to neurogenic bladder dysfunction from
      January 2010 to March 2013. Sixty-two episodes of cystitis occurred in 27
      patients. Seventy bacterial strains were isolated from urine samples. The rate of
      Gram-negative bacteria was 84.3%. Six extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli (E. coli) strains were isolated from 4 patients. An
      ESBL-producing Proteus mirabilis strain and a methicillin-resistant
      Staphylococcus aureus strain were isolated from one patient each. Most of the
      pathogens of cystitis in the pediatric patients with CIC were Gram-negative
      bacilli, especially E. coli. We should be aware that ESBL producing E. coli as
      potential pathogens cause cystitis and regularly survey antimicrobial
      susceptibility to understand the resistant strains that develop.

PMID- 26194975
TI  - Distinct actin oligomers modulate differently the activity of actin nucleators.
AB  - Polymerization of actin monomers into filaments requires the initial formation of
      nuclei composed of a few actin subunits; however, their instability has hindered
      their detailed study. Therefore we used chemically crosslinked actin oligomers to
      analyse their effect on actin polymerization. Actin dimer (upper dimer, UD),
      trimer and tetramer intermolecularly crosslinked by phenylene-bismaleimide along
      the genetic helix (between Lys199 and Cys374) were isolated by gel filtration and
      found to increasingly stimulate actin polymerization as shown by the pyrene assay
      and total internal reflection fluorescence microscopy. In contrast, the so-called
      lower actin dimer (LD) characterized by a Cys374-Cys374 crosslink stimulated
      actin polymerization only at low but inhibited it at high concentrations. UD and
      trimer stimulated the repolymerization of actin from complexes with thymosin
      beta4 (Tbeta4) or profilin, whereas the LD stimulated repolymerization only from
      the profilin : actin but not the actin : Tbeta4 complex. In vivo, actin
      polymerization is stimulated by nucleation factors. Therefore the interaction and
      effects of purified LD, UD and trimer on the actin-nucleating activity of
      gelsolin, mouse diaphanous related (mDia) formin and the actin-related protein
      2/3 (Arp2/3) complex were analysed. Native gel electrophoresis demonstrated
      binding of LD, UD and trimer to gelsolin and its fragment G1-3, to the FH2
      domains of the formins mDia1 and mDia3, and to Arp2/3 complex. UD and trimer
      increased the nucleating activity of gelsolin and G1-3, but not of the mDia-FH2
      domain nor of the Arp2/3 complex. In contrast, LD at equimolar concentration to
      Arp2/3 complex stimulated its nucleating activity, but inhibited that of mDia-FH2
      domains, gelsolin and G1-3, demonstrating differential regulation of their
      nucleating activity by dimers containing differently oriented actin subunits.

PMID- 26194976
TI  - Effect of silver nanoparticle geometry on methicillin susceptible and resistant
      Staphylococcus aureus, and osteoblast viability.
AB  - Orthopedic implant failure as a result of bacterial infection affects
      approximately 0.5-5% of patients. These infections are often caused by
      Staphylococcus aureus which is capable of attaching and subsequently forming a
      biofilm on the implant surface, making it difficult to eradicate with systemic
      antibiotics. Further, with the emergence of antibiotic-resistant bacteria,
      alternative treatments are necessary. Silver nanoparticles have received much
      attention for their broad spectrum antibacterial activity which has been reported
      to be both size and shape dependent. The purpose of this study was therefore to
      evaluate the effect of three different geometries on their effect on microbial
      susceptibility as well as evaluate their effect on bone cell viability. Silver
      nanoparticles of spherical, triangular and cuboid shapes were synthesized by
      chemical reduction methods. The susceptibility of S. aureus and methicillin
      resistant S. aureus was evaluated a 24 h period and determined using a
      colorimetric assay. Further, the viability of human fetal osteoblast (hFOB) cells
      in the presence of the silver nanoparticles was evaluated over a period of 7 days
      by AlmarBlue fluorescence assay. hFOB morphology was also evaluated by light
      microscopy imaging. Results indicated that silver nanoparticle geometry did not
      have an effect on microbiota susceptibility or hFOB viability. However, high
      concentrations of silver nanoparticles (0.5 nM) conferred significant
      susceptibility towards the bacteria and significantly reduced hFOB viability. It
      was also found that the hFOBs exhibited an increasingly reduced viability to
      lower silver nanoparticle concentrations with an increase in exposure time.

PMID- 26194977
TI  - Inhibition of pathogenic bacterial growth on excision wound by green synthesized
      copper oxide nanoparticles leads to accelerated wound healing activity in Wistar
      Albino rats.
AB  - An impaired wound healing is one of the major health related problem in diabetic
      and non-diabetic patients around the globe. The pathogenic bacteria play a
      predominant role in delayed wound healing, owing to interaction in the wound
      area. In our previous work we developed green chemistry mediated copper oxide
      nanoparticles using Ficus religiosa leaf extract. In the present study we make an
      attempt to evaluate the anti-bacterial, and wound healing activity of green
      synthesized copper oxide nanoparticles in male Wistar Albino rats. The agar well
      diffusion assay revealed copper oxide nanoparticles have substantial inhibition
      activity against human pathogenic strains such as Klebsiella pneumoniae, Shigella
      dysenteriae, Staphylococcus aureus, Salmonella typhimurium and Escherichia coli,
      which were responsible for delayed wound healing process. Furthermore, the
      analyses results of wound closure, histopathology and protein profiling confirmed
      that the F. religiosa leaf extract tailored copper oxide nanoparticles have
      enhanced wound healing activity in Wistar Albino rats. 

PMID- 26194978
TI  - Cascade Screening in Familial Hypercholesterolemia: Advancing Forward.
AB  - Familial hypercholesterolemia is a genetic disorder associated with elevated LDL
      cholesterol and high lifetime cardiovascular risk. Both clinical and molecular
      cascade screening programs have been implemented to increase early definition and
      treatment. In this systematic review, we discuss the main issues found in 65
      different articles related to cascade screening and familial
      hypercholesterolemia, covering a range of topics including different
      types/strategies, considerations both positive and negative regarding cascade
      screening in general and associated with the different strategies, cost and
      coverage consideration, direct and indirect contact with patients, public policy
      around life insurance and doctor-patient confidentiality, the "right to know,"
      and public health concerns regarding familial hypercholesterolemia. 

PMID- 26194979
TI  - Hepatic Lipase: a Comprehensive View of its Role on Plasma Lipid and Lipoprotein
      Metabolism.
AB  - Hepatic lipase (HL) is a key enzyme catalyzing the hydrolysis of triglycerides
      (TG) and phospholipids (PLs) in several lipoproteins. It is generally recognized
      that HL is involved in the remodeling of remnant, low-density lipoprotein (LDL),
      high-density lipoprotein (HDL) and the production of small, dense low-density
      lipoproteins (sd-LDLs).On the other hand, it is unclear whether HL accelerates or
      retards atherosclerosis. From the clinical point of view, HL deficiency may
      provide useful information on answering this question, but the rarity of this
      disease makes it impossible to conduct epidemiological study.In this review, we
      describe a comprehensive and updated view of the clinical significance of HL on
      lipid and lipoprotein metabolism. 

PMID- 26194980
TI  - Time Course for Onset and Recovery from Effects of a Novel Male Reproductive
      Toxicant: Implications for Apical Preclinical Study Designs.
AB  - In the pharmaceutic ICH S5(R2) guidelines for reproductive toxicity testing, a
      premating dose duration of 14 days is considered sufficient for assessment of
      male fertility for compounds that are not testicular toxicants. A novel alpha7
      subtype of nicotinic acetylcholine receptor (alpha7nAChR) agonist, originally
      intended for treatment of Alzheimer's disease, did not cause changes in sperm
      counts, motility, or testicular histopathology in rat toxicity studies of up to 6
      months duration. However, profound decrements in male fertility (reduced
      pregnancy rates and litter sizes) occurred after 11 weeks of dosing in male rats.
      In two time-course investigations, dosed male rats were paired with undosed
      females after 5, 14, and 28 daily doses and again after 2 and 4 weeks off-dose.
      Effects on male fertility were undetectable after 5 days. After 14 days, there
      was no effect on pregnancy rate, but preimplantation losses were increased.
      Effects on both pregnancy rates and preimplantation losses were clearly
      detectable after 28 days, but were of lesser magnitude than after 11 weeks of
      dosing. Fertility recovered rapidly after dose cessation. These studies
      illustrate the sensitivity of a long premating dose period at revealing hazard
      and determining the magnitude of effect on male fertility for compounds that are
      intended for chronic administration and do not affect testicular histopathology. 

PMID- 26194981
TI  - Antibodies to m-type phospholipase A2 receptor in children with idiopathic
      membranous nephropathy.
AB  - Idiopathic membranous nephropathy (IMN), the commonest cause of adult nephrotic
      syndrome (NS), accounts for only a minority of paediatric NS. Antibodies to m
      type phospholipase A2 receptor (PLA2R) are seen in two-thirds of adult IMN cases.
      PLA2R staining in glomerular deposits is observed in 74% and 45% of adult and
      paediatric IMN cases, respectively. However, there are no reports of anti-PLA2R
      in paediatric IMN. We evaluated anti-PLA2R levels and PLA2R in gloemrular
      deposits in paediatric IMN seen at our center. Five cases were enrolled, all the
      cases stained for PLA2R in glomeruli and three (60%) had antibodies to PLA2R
      antigen. There was a parellel reduction in proteinuria and anti-PLA2R titer. The
      present report suggests that PLA2R has a contributory role in the pathogenesis of
      paediatric IMN.

PMID- 26194982
TI  - Dimethylarginines as biomarkers for the kidney transplant management in
      methylmalonic aciduria.
AB  - Methylmalonic aciduria (MMA) is an inborn error of metabolism associated with
      many complications despite treatment. Chronic renal failure is the most common
      problem, and patients may eventually require kidney transplant. Therefore, it is
      worth investigating whether living donor kidney transplant offers a better option
      than deceased kidney donors; and the value of novel vascular risk biomarkers in
      the assessment of transplanted MMA patients. We report a case of a 26-year-old
      man with MMA, who progressed to end-stage renal disease and received kidney
      transplant from a heterozygous next-of-kin living donor at 20 years of age.
      Although post-transplant urinary levels of methylmalonic acid decreased, this
      reduction was lower than previously reported for deceased donors. No episodes of
      metabolic decompensation were observed after transplantation. During his clinical
      progress, vascular complications appeared; and finally, pancreatitis was the
      cause of death. After kidney transplant, we evaluated novel vascular risk
      factors, such as asymmetric dimethylarginine (ADMA) and symmetric
      dimethylarginine (SDMA), which were used as early biomarkers of progression and
      metabolic management for this transplanted patient. This case report illustrates
      the disadvantage of transplantation with an allograft from a heterozygous living
      donor, and the utility of vascular risk biomarkers in renal transplant
      assessment. 

PMID- 26194983
TI  - Acute cholecystitis in a peritoneal dialysis patient: percutaneous trans-hepatic
      gallbladder drainage is a challenging therapeutic option.

PMID- 26194984
TI  - Novel COL4A3 gene mutations in a consanguineous family with autosomal recessive
      Alport syndrome.

PMID- 26194985
TI  - Abdominal pain, emesis and dyspnea after kidney transplantation.

PMID- 26194986
TI  - Hypocalcaemic tetany occurring post a single denosumab dose in a patient with
      stage 4 chronic kidney disease, followed by calcium- and calcitriol-induced
      hypercalcaemia.

PMID- 26194987
TI  - Response to Wiwanitkit et al. comment on the report: 'A randomised trial
      investigating the safety and efficacy of influenza vaccination in patients with
      ANCA-associated vasculitis'.

PMID- 26194988
TI  - A versatile test for equality of two survival functions based on weighted
      differences of Kaplan-Meier curves.
AB  - With censored event time observations, the logrank test is the most popular tool
      for testing the equality of two underlying survival distributions. Although this
      test is asymptotically distribution free, it may not be powerful when the
      proportional hazards assumption is violated. Various other novel testing
      procedures have been proposed, which generally are derived by assuming a class of
      specific alternative hypotheses with respect to the hazard functions. The test
      considered by Pepe and Fleming (1989) is based on a linear combination of
      weighted differences of the two Kaplan-Meier curves over time and is a natural
      tool to assess the difference of two survival functions directly. In this
      article, we take a similar approach but choose weights that are proportional to
      the observed standardized difference of the estimated survival curves at each
      time point. The new proposal automatically makes weighting adjustments
      empirically. The new test statistic is aimed at a one-sided general alternative
      hypothesis and is distributed with a short right tail under the null hypothesis
      but with a heavy tail under the alternative. The results from extensive numerical
      studies demonstrate that the new procedure performs well under various general
      alternatives with a caution of a minor inflation of the type I error rate when
      the sample size is small or the number of observed events is small. The survival
      data from a recent cancer comparative study are utilized for illustrating the
      implementation of the process.

PMID- 26194989
TI  - Effects of reduced glutathione on acrosin activity in frozen-thawed boar
      spermatozoa.
AB  - In pigs, acrosin activity in extended semen is correlated with reproductive
      performance and has recently been identified as a freezability marker. Reduced
      glutathione (GSH) is known to decrease sperm cryodamage and increase the
      reproductive performance of frozen-thawed boar spermatozoa. However, the effects
      of GSH on the acrosin activity of good and poor freezability ejaculates (GFE and
      PFE, respectively) is yet to be examined. The present study investigated how
      supplementing cryopreservation media with GSH affected acrosin activity in GFE
      and PFE, as well as the relationship between acrosin activity and reproductive
      performance in frozen-thawed boar spermatozoa. In addition, we examined whether
      the increase in fertility rates and litter sizes observed after the addition of
      2mM GSH to cryopreservation extenders was related to acrosin activity.
      Supplementing freezing media with 2mM GSH partially counteracted the
      cryopreservation-related decrease in acrosin activity in GFE but not PFE. Acrosin
      activity was found to be significantly correlated with in vivo reproductive
      performance of frozen-thawed boar semen. In conclusion, the effects of adding GSH
      to freezing extenders on the acrosin activity of frozen-thawed boar spermatozoa
      rely on the intrinsic freezability of the ejaculate. Furthermore, the maintenance
      of proper acrosin activity could contribute to the increase in reproductive
      performance mediated by GSH.

PMID- 26194990
TI  - Conversion during laparoscopic colorectal resections: a complication or a
      drawback? A systematic review and meta-analysis of short-term outcomes.
AB  - PURPOSE: Several studies compared the outcomes of laparoscopically completed
      colorectal resections (LCR) to those requiring conversion to open surgery (COS).
      However, a comparative analysis between COS patients and patients undergoing
      planned open surgery (POS) would be useful to clarify if the conversion can be
      considered a simple drawback or a complication, being cause of additional
      postoperative morbidity. The aim of this study is to perform a meta-analysis of
      current evidences comparing postoperative outcomes of COS patients to POS
      patients. METHODS: A systematic search of Medline, ISI Web of Knowledge, and
      Scopus was performed to identify studies reporting short-term outcomes of COS and
      POS patients. Primary outcomes were 30-day overall morbidity and length of
      postoperative hospital stay. Data were analyzed with fixed-effect modeling, and
      sensitivity analyses were performed to test the robustness of the results.
      RESULTS: Twenty studies involving 30,656 patients undergoing POS and 1935 COS
      patients were selected. The mean conversion rate was 0.17. Similar 30-day overall
      morbidity and length of postoperative hospital stay were found in COS and POS
      patients. Wound infection (OR 1.43, 95 % CI 1.12 to 1.83, p < 0.01) was higher in
      the COS group. Other results were robust. Outcomes were comparable for patients
      undergoing resection for different natures of the disease (benign vs. malignant)
      and at different sites (colon vs. rectum). CONCLUSION: Conversions from
      laparoscopic to open procedure during colorectal resection are not associated
      with a poorer postoperative outcome compared to patients undergoing planned open
      surgery, except for a higher risk of wound infection.

PMID- 26194991
TI  - Minimally invasive liver surgery in a hepato-biliary unit: learning curve and
      indications.
AB  - Operative indications and type of resection represent a crucial issue of
      minimally invasive liver surgery (MILS), and they should not be modified by the
      increased experience of laparoscopic liver surgeons. The aim of this study was to
      define the indications for MILS and the learning curve in a high-volume
      hepatobiliary surgery Unit. Between 2009 and 2014, 993 liver resections were
      performed in our unit, and MILS was performed in 81 of these (8.2%). The
      proportion of MILS significantly increased over the study period of time and was
      significantly higher during the last 2 years than during the first 2 years (10.8
      vs. 6.4%; p = 0.042). Rate of liver resections for benign disease between the
      first 2 years and the last 2 years of the study period was not significantly
      different (14.7 vs. 10.5%; p = 0.098). Rate of MILS for malignant disease
      significantly increased from the first 2 years to the last 2 years: 3.2 vs. 7.5%
      (p < 0.001). Indication for left lateral sectionectomy in the whole series was
      rare. It was performed in 37 cases as the only liver surgical procedure, on 993
      liver resections (3.7%). In 25 (67.6%) of these, a minimally invasive approach
      was used. Rate of left lateral sectionectomies between the first 2 years and the
      last 2 years of the study period was not significantly different: 4.5 vs. 3.8% (p
      = 0.645). This study shows that the proportion of MILS significantly increased
      over the study period of time in our high-volume hepatobiliary surgery Unit
      without changing surgical indications for benign disease and type of resections.

PMID- 26194992
TI  - Procalcitonin levels in schizophrenic patients and patients with sepsis.

PMID- 26194993
TI  - A dangerous method? The use of induced pluripotent stem cells as a model for
      schizophrenia.
AB  - Schizophrenia is a devastating and prevalent psychiatric illness. Progress in
      understanding the basic pathophysiological processes underlying this disorder has
      been hindered by the lack of appropriate models. With the advent of induced
      pluripotent stem cell (iPSC) technology, it is now possible to generate live
      neurons in vitro from somatic tissue of schizophrenia patients. Despite its
      several limitations, this revolutionary technology has already helped to advance
      our understanding of schizophrenia. The phenotypic insights garnered with iPSC
      models of schizophrenia include transcriptional dysregulation, oxidative stress
      synaptic dysregulation, and neurodevelopmental abnormalities. Potential pitfalls
      of this work include the possibility of introducing random genetic mutations
      during the reprogramming process, the inadequacy of using neurons from other
      patients as controls, the inability to capture the complex environmental
      contribution to schizophrenia pathogenesis, the difficulty in modelling
      neurodevelopment, and the difficulty in modelling the interaction of multiple
      neuronal and non-neuronal cell types. However, with the increasing sophistication
      of available reprogramming techniques, co-culture technology, and gene correction
      strategies, iPSC-derived neurons will continue to elucidate how neuronal function
      is disrupted in schizophrenia. 

PMID- 26194995
TI  - The current state of respiratory research in the UK.

PMID- 26194994
TI  - Molecular dynamics studies of aqueous silica nanoparticle dispersions: salt
      effects on the double layer formation.
AB  - The ion distribution around hydroxylated silica nanoparticles (NP-H) dispersed in
      brine was investigated by fully atomistic molecular dynamics. The NP-H
      dispersions in aqueous electrolyte media are simulated in solutions of varying
      salinity (NaCl, CaCl2, and MgCl2), salt concentration (0.06  *  10(-3) to 3.00  *
      10(-3) mole fraction [Formula: see text]), and temperature (300 and 350 K) at 1
      atm. The NP-H models reproduce the observed experimental concentration of silanol
      and geminal surface sites, which are responsible for local charge variations on
      the nanoparticles' surface. Interestingly, under certain salt concentration
      conditions, the formation of an electrical double layer (DL) around the overall
      neutral NP-H occurs. The resulting DLs are attenuated with increasing temperature
      for all evaluated salts. With increasing salt concentration, a sign inversion of
      the effective charge at the first ion layer is observed, which modifies the
      electrostatic environment around the nanoparticle. The minimum salt concentration
      that leads to a DL formation at 300 K is 1.05  *  10(-3), 0.37  *  10(-3), and
      0.06  *  10(-3) chis for NaCl, CaCl2, and MgCl2, respectively. The width of the
      DL decreases sequentially in ionic strength from NaCl to CaCl2 to MgCl2, which is
      similar to that found for highly charged surfaces. These results are in line with
      our previous experimental data for negative charged NP-H. All together, these
      observations suggest an interplay mechanism between the formation and narrowing
      of electric double layers on the stability of NP dispersions in both neutral and
      negatively charged NP-H.

PMID- 26194996
TI  - Neural respiratory drive predicts clinical deterioration and safe discharge in
      exacerbations of COPD.
AB  - RATIONALE: Hospitalised patients with acute exacerbation of COPD may deteriorate
      despite treatment, with early readmission being common. OBJECTIVES: To
      investigate whether neural respiratory drive, measured using second intercostal
      space parasternal muscle electromyography (EMGpara), would identify worsening
      dyspnoea and physician-defined inpatient clinical deterioration, and predict
      early readmission. METHODS: Patients admitted to a single-site university
      hospital with exacerbation of COPD were enrolled. Spirometry, inspiratory
      capacity (IC), EMGpara, routine physiological parameters, modified early warning
      score (MEWS), modified Borg scale for dyspnoea and physician-defined episodes of
      deterioration were recorded daily until discharge. Readmissions at 14 and 28 days
      post discharge were recorded. MEASUREMENTS AND MAIN RESULTS: 120 patients were
      recruited (age 70 +/- 9 years, forced expiratory volume in 1 s (FEV1) of 30.5 +/-
      11.2%). Worsening dyspnoea, defined as at least one-point increase in Borg scale,
      was associated with increases in EMGpara%max and MEWS, whereas an increase in
      EMGpara%max alone was associated with physician-defined inpatient clinical
      deterioration. Admission-to-discharge change (Delta) in the normalised value of
      EMGpara (DeltaEMGpara%max) was inversely correlated with DeltaFEV1 (r = -0.38, p
      < 0.001) and DeltaIC (r = -0.44, p < 0.001). DeltaEMGpara%max predicted 14-day
      readmission (OR 1.13, 95% 1.03 to 1.23) in the whole cohort and 28-day
      readmission in patients under 85 years (OR 1.09, 95% CI 1.01 to 1.18). Age (OR
      1.08, 95% CI 1.03 to 1.14) and 12-month admission frequency (OR 1.29, 1.01 to
      1.66), also predicted 28-day readmission in the whole cohort. CONCLUSIONS:
      Measurement of neural respiratory drive by EMGpara represents a novel
      physiological biomarker that may be helpful in detecting inpatient clinical
      deterioration and identifying the risk of early readmission among patients with
      exacerbations of COPD. TRIAL REGISTRATION: NCT01361451.

PMID- 26194997
TI  - Use of controversial ACC/AHA guidelines for statin therapy is supported by US
      studies.

PMID- 26194999
TI  - Fine-scale population structure of Malays in Peninsular Malaysia and Singapore
      and implications for association studies.
AB  - Fine scale population structure of Malays - the major population in Malaysia, has
      not been well studied. This may have important implications for both evolutionary
      and medical studies. Here, we investigated the population sub-structure of Malay
      involving 431 samples collected from all states from peninsular Malaysia and
      Singapore. We identified two major clusters of individuals corresponding to the
      north and south peninsular Malaysia. On an even finer scale, the genetic
      coordinates of the geographical Malay populations are in correlation with the
      latitudes (R(2) = 0.3925; P = 0.029). This finding is further supported by the
      pairwise FST of Malay sub-populations, of which the north and south regions
      showed the highest differentiation (FST [North-south] = 0.0011). The collective
      findings therefore suggest that population sub-structure of Malays are more
      heterogenous than previously expected even within a small geographical region,
      possibly due to factors like different genetic origins, geographical isolation,
      could result in spurious association as demonstrated in our analysis. We suggest
      that cautions should be taken during the stage of study design or interpreting
      the association signals in disease mapping studies which are expected to be
      conducted in Malay population in the near future. 

PMID- 26195000
TI  - The adoption of a new diagnostic technology for tuberculosis in two Brazilian
      cities from the perspective of patients and healthcare workers: a qualitative
      study.
AB  - BACKGROUND: This article presents the qualitative component linked to a larger
      study of implementation of the XpertTM MTB/Rif technology in two Brazilian
      cities. Despite intrinsic advantages of new health technologies, its introduction
      can be disruptive to existing routines, and it is thus important to understand
      how these innovations are perceived by the different groups involved in its
      regular use. METHODS: This study was based on semi-structured interviews with
      patients, lab technicians, health care workers and managers involved with
      diagnosis and care of Tuberculosis (TB). The interviews had their content
      analyzed in order to abstract the different perspectives for the various actors.
      RESULTS: For patients the changes were not perceived as significant, since their
      greatest concerns were related to treatment and the stigma associated with TB.
      The professionals in general welcomed the new technique, which dramatically
      decreases the workload, time and reliability of diagnosis, in their view.
      However, we noted difficulties with the concomitant implementation of new IT
      technology for recording and reporting test results, which negatively impacted
      the time necessary to get lab diagnosis to physicians. CONCLUSIONS: Through this
      analysis we detected some bottlenecks in the surrounding environment, not
      necessarily linked to the technology itself but which could hamper considerably
      its advantages.

PMID- 26195001
TI  - Impact of daily supplementation of Spirulina platensis on the immune system of
      naive HIV-1 patients in Cameroon: a 12-months single blind, randomized,
      multicenter trial.
AB  - BACKGROUND: Micronutrient deficiencies occur early in Human Immunodeficiency
      Virus (HIV) infections they have reverse effects on the nutritional status. The
      diet supplementation with a natural nutraceutical rich in proteins and
      micronutrient like Spirulina platensis, may be effective and efficient in
      delaying HIV disease progression by frequently reported improvement in immune
      response. METHODS: A prospective single-blind, randomized, multicenter study
      conducted on 320 HIV-1 ARV-naive participants for 12 months. Participants
      received either S. platensis supplementation and standard care or standard care
      and local balanced diet without S. platenis. Selected hematological and
      biochemical as well as CD4 count cells, viral load copies were assessed at three
      separate times. RESULTS: Among the 169 ART-naive participants enrolled in the
      study, the female was mostly represented (67.1%). The significant increase of CD4
      count cells (596.32-614.92 cells count) and significant decrease of viral load
      levels (74.7 * 10(3)-30.87 * 10(3) copies/mL) of the patients who received a
      supplementation of S. platensis was found after 6 months of treatment.
      Haemoglobin level was also significantly higher in the same group while the
      fasting blood glucose concentration decreased after 12 months compared to
      control. CONCLUSION: A daily supplementation with S. platensis to diet combined
      with a reasonable balanced diet has significantly increased the CD4 cells and
      reduced the viral load after 6 months. Further studies are recommended among a
      large specific group of people infected by the HIV in order to investigate the
      mechanisms involved on the effect of S. platensis on immune system.

PMID- 26195002
TI  - Chlamydia trachomatis, Neisseria gonorrhoeae and syphilis among men who have sex
      with men in Brazil.
AB  - BACKGROUND: Sexually transmitted diseases (STD) are frequently asymptomatic and
      increase the likelihood of transmitting and acquiring HIV. In Brazil, the
      guidelines for STDs diagnosis and treatment are based on the syndromic approach.
      Nucleic acid amplification tests (NAAT) has been recommended as routine STDs
      screening in some countries, especially for men who have sex with men (MSM).
      Limited data are available about how to best define target groups for routine
      screening by NAATs within this population. We aimed to assess the prevalence of
      rectal and urethral Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)
      infections and syphilis, and the factors associated with having at least one STD
      among HIV-infected and uninfected MSM in Rio de Janeiro, Brazil. METHODS: From
      August 2010 to June 2012, 391 MSM were enrolled into the Evandro Chagas National
      Institute of Infectious Diseases-INI-Fiocruz cohort, and 292 MSM (HIV
      infected:211 and HIV-uninfected:81) were included in this study. NAATs were
      performed on the rectal swabs and urine for CT and NG. The rapid plasma reagin
      test and microhemagglutination assay for Treponema pallidum were performed for
      syphilis diagnosis. RESULTS: The overall prevalence of STD was 20.0% (95%CI:15.7
      25.1): 10% anorectal chlamydia; syphilis 9.9%; anorectal gonorrheae 2.5%; and
      urethral chlamydia 2.2%; no case of urethral gonorrheae was detected. The
      proportion of HIV-positive MSM who had at least one STD was nearly two times that
      of HIV-negative MSM (22.6% vs 13.2%; P = 0.09). The frequency of each STD, except
      for anorectal NG (1.5% vs.5.2%), was higher among HIV-positive than HIV-negative
      individuals. Among the 211 asymptomatic participants, 17.5% (n = 37) were
      identified as having at least one STD; 10.4% (n = 22/211) tested positive for
      anorectal chlamydia. Sixty five percent of HIV-positive MSM were asymptomatic at
      the time of the STD diagnosis, while 100.0% of the HIV-negative MSM. Age (APR =
      0.78; 95%CI:0.60-1.00 for each additional ten years) and a positive-HIV
      serostatus (APR = 2.05; 95%CI:1.03-4.08) were significantly associated with STD
      diagnosis. CONCLUSION: An overall high STD-prevalence rate was observed,
      especially among HIV-infected and in younger individuals, and the majority of
      STDs were asymptomatic. STD screening using NAATs among asymptomatic MSM is a
      potentially cost-effective intervention for the prevention of HIV infection among
      MSM.

PMID- 26195003
TI  - The importance of plasma D-2HG measurement in screening for IDH mutations in
      acute myeloid leukaemia.

PMID- 26195004
TI  - Troponin in diabetic patients with and without chronic coronary artery disease.
AB  - BACKGROUND: Cardiac-specific troponin detected with the new high-sensitivity
      assays can be chronically elevated in response to cardiovascular comorbidities
      and confer important prognostic information, in the absence of unstable coronary
      syndromes. Both diabetes mellitus and coronary artery disease are known
      predictors of troponin elevation. It is not known whether diabetic patients with
      coronary artery disease have different levels of troponin compared with diabetic
      patients with normal coronary arteries. To investigate this question, we
      determined the concentrations of a level 1 troponin assay in two groups of
      diabetic patients: those with multivessel coronary artery disease and those with
      angiographically normal coronary arteries. METHODS: We studied 95 diabetic
      patients and compared troponin in serum samples from 50 patients with coronary
      artery disease (mean age = 63.7, 58 % male) with 45 controls with
      angiographically normal coronary arteries. Brain natriuretic peptide and the
      oxidative stress biomarkers myeloperoxidase, nitrotyrosine and oxidized LDL were
      also determined. RESULTS: Diabetic patients with coronary artery disease had
      higher levels of troponin than did controls (median values, 12.0 pg/mL (95 %
      CI:10-16) vs 7.0 pg/mL (95 % CI: 5.9-8.5), respectively; p = 0.0001). The area
      under the ROC curve for the diagnosis of CAD was 0.712 with a sensitivity of 70 %
      and a specificity of 66 %. Plasma BNP levels and oxidative stress variables
      (myeloperoxidase, nitrotyrosine, and oxidized LDL) were not different between the
      two groups. In a multivariate analysis, gender (p = 0.04), serum glucose (0.03)
      and Troponin I (p = 0.01) had independent statistical significance. CONCLUSION:
      Troponin elevation is related to the presence of chronic coronary artery disease
      in diabetic patients with multiple associated cardiovascular risk factors.
      Troponin may serve as a biomarker in this high-risk population. TRIAL
      REGISTRATION: http://www.controlled-trials.com REGISTRATION NUMBER:
      ISRCTN26970041.

PMID- 26195005
TI  - Use of computed tomography to compare two femoral head and neck excision
      ostectomy techniques as performed by two novice veterinarians.
AB  - OBJECTIVES: To compare the results of femoral head and neck excision (FHNE)
      ostectomy performed by two novice veterinarians using an osteotome and mallet or
      microsagittal saw. METHODS: In this ex vivo cadaveric study, hindlimbs of eight
      canine cadavers were randomized to FHNE with osteotome or micro sagittal saw as
      performed by two recently graduated veterinarians. The hindimbs were imaged by
      computed tomography (CT) before and after the osteotomy. Post FHNE CT images were
      evaluated by a board certified radiologist blinded to the ostectomy technique for
      assessment of the number of bone fragments, fissures, smoothness of osteotomy
      margination, and volume of residual femoral neck. RESULTS: Femoral head and neck
      excision performed with the osteotome produced more peri-ostectomy bone
      fragments, cortical fissures, irregular margins, and residual femoral neck
      volume, compared with osteotomy using a saw. CLINICAL RELEVANCE: Compared to FHNE
      performed with a sagittal saw, osteotome FHNE resulted in a greater bone trauma
      and residual neck bone volume, which would require post-ostectomy modification in
      a clinical setting.

PMID- 26195006
TI  - Comparative Evaluation of Two Methods for Preparative Fractionation of
      Proteinaceous Subvisible Particles--Differential Centrifugation and FACS.
AB  - PURPOSE: The goal of this study was to compare and evaluate two preparative
      techniques for fractionation of proteinaceous subvisible particles. This work
      enables future studies to address the potential biological consequences of
      proteinaceous subvisible particles in protein therapeutic products. METHODS:
      Particles were generated by heat stress and separated by size using differential
      centrifugation and FACS (Fluorescence-activated cell sorter). Resulting fractions
      were characterized by size-exclusion chromatography, light obscuration, flow
      imaging microscopy and resonant mass measurement. RESULTS: Here we report the
      optimization and comprehensive evaluation of two methods for preparative
      fractionation of subvisible proteinaceous particles into distinct size fractions
      in the range between 0.25 and 100 MUm: differential centrifugation and FACS.
      Using these methods, well-defined size fractions were prepared and characterized
      in detail. Critical assessment and comparison of the two techniques demonstrated
      their complementarity and for the first time-their relative advantages and
      drawbacks. CONCLUSIONS: FACS and differential centrifugation are valuable tools
      to prepare well-defined size-fractions of subvisible proteinaceous particles.
      Both techniques possess unique and advantageous attributes and will likely find
      complementary application in future research on the biological consequences of
      proteinaceous subvisible particles.

PMID- 26195007
TI  - In Silico Estimation of Skin Concentration Following the Dermal Exposure to
      Chemicals.
AB  - PURPOSE: To develop an in silico method based on Fick's law of diffusion to
      estimate the skin concentration following dermal exposure to chemicals with a
      wide range of lipophilicity. METHODS: Permeation experiments of various chemicals
      were performed through rat and porcine skin. Permeation parameters, namely,
      permeability coefficient and partition coefficient, were obtained by the fitting
      of data to two-layered and one-layered diffusion models for whole and stripped
      skin. The mean skin concentration of chemicals during steady-state permeation was
      calculated using the permeation parameters and compared with the observed values.
      RESULTS: All permeation profiles could be described by the diffusion models. The
      estimated skin concentrations of chemicals using permeation parameters were close
      to the observed levels and most data fell within the 95% confidence interval for
      complete prediction. The permeability coefficient and partition coefficient for
      stripped skin were almost constant, being independent of the permeant's
      lipophilicity. CONCLUSIONS: Skin concentration following dermal exposure to
      various chemicals can be accurately estimated based on Fick's law of diffusion.
      This method should become a useful tool to assess the efficacy of topically
      applied drugs and cosmetic ingredients, as well as the risk of chemicals likely
      to cause skin disorders and diseases.

PMID- 26195008
TI  - Obituary: Paul M. Bummer (1955 - 2015).

PMID- 26195010
TI  - Influence of Steric Crowding on Diastereoselective Arabinofuranosylations.
AB  - The occurrence of arabinofuranosides on the cell surface of Mycobacterium
      tuberculosis (Mtb) and their significance in controlling disease spurred interest
      in developing strategies for their diastereoselective synthesis. Mtb uses enzymes
      to achieve diastereoselectivity through noncovalent interactions. Of the two
      possible glycosidic linkages, chemically, 1,2-trans linkage is relatively easy to
      synthesize by taking advantage of neighboring group participation, whereas
      synthesis of the 1,2-cis linkage is notoriously difficult. In this article,
      stereochemical effects on the diastereoselectivity of arabinofuranosidation are
      investigated with thiopyridyl, imidate, and thiotolyl donors as well as
      differently crowded glycosyl acceptors; subtle differences in the stereochemical
      environment of the acceptors were observed to alter the diastereoselectivity of
      the furanoside formation. Results from this endeavor suggest that 1,2-cis
      arabinofuranosides can be synthesized conveniently by conducting the reaction at
      lower temperature on sterically demanding and less reactive substrates. 

PMID- 26195011
TI  - [Fillet flap for axillary reconstruction].
AB  - INTRODUCTION: Among all complications that affect patients with
      neurofibromatosis, type I (NF1) are very aggressive malignant nerve sheath tumors
      (MPNSTs). Surgery is their first line therapy. CLINICAL CASE: We report the case
      of a non metastatic neurofibrosarcoma of the axillary area in a 22-year-old male
      with NF1. An interscapulothoracic resection was performed to resect the tumor and
      had sacrificed the homolateral latissimus dorsi pedicled myocutaneous flap. In
      this extreme and not codified situation, the coverage of the tissue loss was
      possible in the same time using a free flap harvested on the amputated limb
      (fillet flap). The free flap based on the humeral pedicle was composed of the
      entire skin and muscles of the amputated forearm. It was anastomosed on the
      subclavian vessels. Only a free flap was suitable in this tissue loss. The use of
      a fillet flap allows a wide and reliable coverage without donor site morbidity.

PMID- 26195012
TI  - [Rehabilitation of facial paralysis].
AB  - Rehabilitation takes an important part in the treatment of facial paralysis,
      especially when these are severe. It aims to lead the recovery of motor activity
      and prevent or reduce sequelae like synkinesis or spasms. It is preferable that
      it be proposed early in order to set up a treatment plan based on the results of
      the assessment, sometimes coupled with an electromyography. In case of surgery,
      preoperative work is recommended, especially in case of hypoglossofacial
      anastomosis or lengthening temporalis myoplasty (LTM). Our proposal is to present
      an original technique to enhance the sensorimotor loop and the cortical control
      of movement, especially when using botulinum toxin and after surgery. 

PMID- 26195013
TI  - [4th Amiens' perforator flap course. 2nd Duplex ultrasound workshop for plastic
      surgeon].

PMID- 26195014
TI  - Forest tree growth response to hydroclimate variability in the southern
      Appalachians.
AB  - Climate change will affect tree species growth and distribution; however, under
      the same climatic conditions species may differ in their response according to
      site conditions. We evaluated the climate-driven patterns of growth for six
      dominant deciduous tree species in the southern Appalachians. We categorized
      species into two functional groups based on their stomatal regulation and xylem
      architecture: isohydric, diffuse porous and anisohydric, ring porous. We
      hypothesized that within the same climatic regime: (i) species-specific
      differences in growth will be conditional on topographically mediated soil
      moisture availability; (ii) in extreme drought years, functional groups will have
      markedly different growth responses; and (iii) multiple hydroclimate variables
      will have direct and indirect effects on growth for each functional group. We
      used standardized tree-ring chronologies to examine growth of diffuse-porous
      (Acer, Liriodendron, and Betula) and ring-porous (Quercus) species vs. on-site
      climatic data from 1935 to 2003. Quercus species growing on upslope sites had
      higher basal area increment (BAI) than Quercus species growing on mesic, cove
      sites; whereas, Acer and Liriodendron had lower BAI on upslope compared to cove
      sites. Diffuse-porous species were more sensitive to climate than ring porous,
      especially during extreme drought years. Across functional groups, radial growth
      was more sensitive to precipitation distribution, such as small storms and dry
      spell length (DSL), rather than the total amount of precipitation. Based on
      structural equation modeling, diffuse-porous species on upslope sites were the
      most sensitive to multiple hydroclimate variables (r(2)  = 0.46), while ring
      porous species on upslope sites were the least sensitive (r(2)  = 0.32). Spring
      precipitation, vapor pressure deficit, and summer storms had direct effects on
      summer AET/P, and summer AET/P, growing season small storms and DSL partially
      explained growth. Decreasing numbers of small storms and extending the days
      between rainfall events will result in significant growth reduction, even in
      regions with relatively high total annual rainfall. 

PMID- 26195015
TI  - Helicobacter pylori Coinfection Is Associated With Decreased Markers of Immune
      Activation in ART-Naive HIV-Positive and in HIV-Negative Individuals in Ghana.
AB  - BACKGROUND: Helicobacter pylori coinfection in human immunodeficiency virus (HIV)
      patients has been associated with higher CD4+ cell counts and lower HIV-1 viral
      loads, with the underlying mechanisms being unknown. The objective of this study
      was to investigate the impact of H. pylori infection on markers of T-cell
      activation in HIV-positive and HIV-negative individuals. METHODS: In a cross
      sectional, observational study, HIV patients (n = 457) and HIV-negative blood
      donors (n = 79) presenting to an HIV clinic in Ghana were enrolled. Data on
      clinical and sociodemographic parameters, CD4+/CD8+ T-cell counts, and HIV-1
      viral load were recorded. Helicobacter pylori status was tested using a stool
      antigen test. Cell surface and intracellular markers related to T-cell immune
      activation and turnover were quantified by flow cytometry and compared according
      to HIV and H. pylori status. RESULTS: Helicobacter pylori infection was
      associated with decreased markers of CD4+ T-cell activation (HLA-DR+CD38+CD4+;
      22.55% vs 32.70%; P = .002), cell proliferation (Ki67; 15.10% vs 26.80%; P =
      .016), and immune exhaustion (PD-1; 32.45% vs 40.00%; P = .005) in 243
      antiretroviral therapy (ART)-naive patients, but not in 214 patients on ART. In
      HIV-negative individuals, H. pylori infection was associated with decreased
      frequencies of activated CD4+ and CD8+ T cells (6.31% vs 10.40%; P = .014 and
      18.70% vs 34.85%, P = .006, respectively). CONCLUSIONS: Our findings suggest that
      H. pylori coinfection effectuates a systemic immune modulatory effect with
      decreased T-cell activation in HIV-positive, ART-naive patients but also in HIV
      negative individuals. This finding might, in part, explain the observed
      association of H. pylori infection with favorable parameters of HIV disease
      progression. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT01897909.

PMID- 26195016
TI  - The Case for Routine Environmental Testing for Legionella Bacteria in Healthcare
      Facility Water Distribution Systems-Reconciling CDC Position and Guidance
      Regarding Risk.

PMID- 26195018
TI  - Reply to Gamage et al.

PMID- 26195019
TI  - Facile Fabrication of Micro-Nano Structured Triboelectric Nanogenerator with High
      Electric Output.
AB  - In this article, a new method is used to fabricate a high-performance
      triboelectric nanogenerator (TENG), which is convenient and cost-effective. A
      polyformaldehyde (POM) film with novel structures is prepared through
      electrospinning and is combined with a polytetrafluoroethylene (PTFE) film to
      assemble micro-nano structured TENG. The short-circuit current (I s) and open
      circuit voltage (V o) of the TENG are up to 0.4343 mA and 236.8 V, respectively,
      and no significant change is observed by applying different frequencies of
      external impact forces from 1 to 10 Hz. Finally, we successfully drive an
      electrochromic device (ECD) directly using TENG within just 2 min for the first
      time. 

PMID- 26195017
TI  - Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of
      Low Disease Incidence.
AB  - BACKGROUND: Lyme disease is diagnosed by 2-tiered serologic testing in patients
      with a compatible clinical illness, but the significance of positive test results
      in low-prevalence regions has not been investigated. METHODS: We reviewed the
      medical records of patients who tested positive for Lyme disease with
      standardized 2-tiered serologic testing between 2005 and 2010 at a single
      hospital system in a region with little endemic Lyme disease. Based on clinical
      findings, we calculated the positive predictive value of Lyme disease serology.
      Next, we reviewed the outcome of serologic testing in patients with select
      clinical syndromes compatible with disseminated Lyme disease (arthritis, cranial
      neuropathy, or meningitis). RESULTS: During the 6-year study period 4723 patients
      were tested for Lyme disease, but only 76 (1.6%) had positive results by
      established laboratory criteria. Among 70 seropositive patients whose medical
      records were available for review, 12 (17%; 95% confidence interval, 9%-28%) were
      found to have Lyme disease (6 with documented travel to endemic regions). During
      the same time period, 297 patients with a clinical illness compatible with
      disseminated Lyme disease underwent 2-tiered serologic testing. Six of them (2%;
      95% confidence interval, 0.7%-4.3%) were seropositive, 3 with documented travel
      and 1 who had an alternative diagnosis that explained the clinical findings.
      CONCLUSIONS: In this low-prevalence cohort, fewer than 20% of positive Lyme
      disease tests are obtained from patients with clinically likely Lyme disease.
      Positive Lyme disease test results may have little diagnostic value in this
      setting.

PMID- 26195021
TI  - Ongoing search for better policies: A response to commentaries'.

PMID- 26195022
TI  - Evaluation of the left ventricle longitudinal deformity using myocardial-tracking
      signals in severely obese adolescents.
AB  - BACKGROUND: The global prevalence of obesity in school-age children and
      adolescents has increased in recent decades. Obesity modifies some aspects of the
      cardiovascular system in order to preserve the body homoeostasis.
      Echocardiography to study ventricular function plays an important role in the
      evaluation of pathological re-modelling associated with left ventricular
      dysfunction. The aim of this study was to evaluate the left ventricle function
      and structure with conventional echocardiography and to analyse the longitudinal
      deformity of the left ventricle using myocardial-tracking signals in a group of
      severely obese adolescents. Methods and results We carried out a descriptive
      cross-sectional study. We describe the evaluation of the left ventricle using
      conventional bi-dimensional echocardiography and the myocardial-tracking signals
      in severely obese adolescents. There were 34 severely obese adolescents included
      in our study; 52% had a left ventricular ejection fraction<55%, the left
      ventricular end-diastolic diameter was increased in 70.5% of patients, and 32.3%
      had an increase in left ventricular mass. On average, 78.9% had abnormal values
      of left ventricle longitudinal deformations. The number of segments affected per
      patient was, on average, 5.8, with the anterior apical segment being the most
      commonly affected. There was a decrease in global longitudinal deformity in 79.4%
      of the cases. CONCLUSION: More than half of this group of asymptomatic severely
      obese adolescents showed abnormalities in left ventricular structure and function
      evaluated using traditional echocardiographic methods, but 100% of the cases
      showed abnormalities in longitudinal deformation in at least one of the 17 left
      ventricle segments evaluated using myocardial-tracking signals.

PMID- 26195020
TI  - Pain, Fatigue, and Psychological Impact on Health-Related Quality of Life in
      Childhood-Onset Lupus.
AB  - OBJECTIVE: To evaluate pain, fatigue, and psychological functioning of childhood
      onset systemic lupus erythematosus (SLE) patients and examine how these factors
      impact health-related quality of life (HRQOL). METHODS: At a tertiary
      rheumatology clinic, 60 childhood-onset SLE patients completed the following: a
      visual analog scale (VAS) of pain intensity (0-10), the Pediatric Quality of Life
      (PedsQL) multidimensional fatigue scale, Pain Coping Questionnaire, Pain
      Catastrophizing Scale (PCS), Children's Depression Inventory I (CDI-I), the
      Screen for Child Anxiety Related Emotional Disorders (SCARED) questionnaire, and
      the PedsQL generic core (GC) scale and rheumatology module (RM).
      Sociodemographics and multiple disease activity indicators were recorded.
      RESULTS: Fatigue was present in 65% of the patients. Clinically relevant pain
      (pain-VAS >3), anxiety (SCARED >=25), and depressive symptoms (CDI-I >12) were
      observed in 40%, 37%, and 30% of the patients, respectively; 22% had high
      catastrophizing (PCS >=26). On average, the PedsQL-GC and -RM scores for
      childhood-onset SLE were lower than in healthy norms. Reduced PedsQL-GC and -RM
      scores were highly correlated with greater levels of fatigue, anxiety, and
      depressive symptoms (Pearson's r > 0.65), but had weak correlation with disease
      activity (Pearson's r < 0.25). Regression analysis demonstrated HRQOL was most
      impacted by fatigue, pain, and anxiety when evaluating all factors concurrently
      (P < 0.001). CONCLUSION: Childhood-onset SLE is associated with decreased HRQOL,
      and psychological aspects of health contribute substantially to low HRQOL,
      whereas measures of childhood-onset SLE activity seem less relevant. Fatigue,
      pain, mood, and anxiety symptoms are present in a large subgroup of patients and
      need medical attention to achieve optimal health outcomes.

PMID- 26195023
TI  - Re-orienting a remote acute care model towards a primary health care approach:
      key enablers.
AB  - INTRODUCTION: The objective of this study was to identify the key enablers of
      change in re-orienting a remote acute care model to comprehensive primary
      healthcare delivery. The setting of the study was a 12-bed hospital in Fitzroy
      Crossing, Western Australia. METHODS: Individual key informant, in-depth
      interviews were completed with five of six identified senior leaders involved in
      the development of the Fitzroy Valley Health Partnership. Interviews were
      recorded and transcripts were thematically analysed by two investigators for
      shared views about the enabling factors strengthening primary healthcare delivery
      in a remote region of Australia. RESULTS: Participants described theestablishment
      of a culturally relevant primary healthcare service, using a community-driven,
      'bottom up' approach characterised by extensive community participation. The
      formal partnership across the government and community controlled health services
      was essential, both to enable change to occur and to provide sustainability in
      the longer term. A hierarchy of major themes emerged. These included community
      participation, community readiness and desire for self-determination; linkages in
      the form of a government community controlled health service partnership;
      leadership; adequate infrastructure; enhanced workforce supply; supportive
      policy; and primary healthcare funding. CONCLUSIONS: The strong united leadership
      shown by the community and the health service enabled barriers to be overcome and
      it maximised the opportunities provided by government policy changes. The
      concurrent alignment around a common vision enabled implementation of change. The
      key principle learnt from this study is the importance of community and health
      service relationships and local leadership around a shared vision for the re
      orientation of community health services.

PMID- 26195024
TI  - A porohyperelastic finite element model of the eye: the influence of stiffness
      and permeability on intraocular pressure and optic nerve head biomechanics.
AB  - Progressively deteriorating visual field is a characteristic feature of primary
      open-angle glaucoma (POAG), and the biomechanics of optic nerve head (ONH) is
      believed to be important in its onset. We used porohyperelasticity to model the
      complex porous behavior of ocular tissues to better understand the effect
      variations in ocular material properties can have on ONH biomechanics. An
      axisymmetric model of the human eye was constructed to parametrically study how
      changes in the permeabilities of retina-Bruch's-choroid complex (k(RBC)), sclera
      k(sclera), uveoscleral pathway (k(UVSC)) and trabecular meshwork k(TM) as well as
      how changes in the stiffness of the lamina cribrosa (LC) and sclera affect IOP,
      LC strains, and translaminar interstitial pressure gradients (TLIPG). Decreasing
      k(RBC) from 5 * 10(- 12) to 5 * 10(- 13) m/s increased IOP and LC strains by 17%,
      and TLIPG by 21%. LC strains increased by 13% and 9% when the scleral and LC
      moduli were decreased by 48% and 50%, respectively. In addition to the trabecular
      meshwork and uveoscleral pathway, the retina-Bruch's-choroid complex had an
      important effect on IOP, LC strains, and TLIPG. Changes in k(RBC) and scleral
      modulus resulted in nonlinear changes in the IOP, and LC strains especially at
      the lowest k(TM) and k(UVSC). This study demonstrates that porohyperelastic
      modeling provides a novel method for computationally studying the biomechanical
      environment of the ONH. Porohyperelastic simulations of ocular tissues may help
      provide further insight into the complex biomechanical environment of posterior
      ocular tissues in POAG.

PMID- 26195025
TI  - Clinical outcomes of allograft with locking compression plates for elderly four
      part proximal humerus fractures.
AB  - BACKGROUND: The aim of this study is to explore the clinical outcomes of
      anatomical allograft or fibula shaft augmentation with locking compression plates
      (LCPs) in elderly patients with four-part proximal humeral fracture (PHF).
      METHODS: A total of 22 elderly patients with four-part PHF underwent allograft
      augmentation with LCPs for treatment. Among them, 7 cases received anatomical
      allograft and 15 patients received fibula shaft. Constant-Murley score (CMS), the
      disability of the arm, shoulder and hand (DASH) score, and subjective ratings,
      radiographic imaging, range of motion (ROM), and complications were recorded as
      postoperative evaluations. RESULTS: Although the ROM and strength were
      considerably limited compared with the normal side, there were no significant
      differences in pain and daily activity between the unaffected and affected sides
      at the last follow-up according to the CMS. Additionally, no significant
      differences were found in the subjective ratings and CMS and DASH scores between
      the patients augmented with fibular shaft and anatomical allograft. Among the 15
      patients who received fibular shaft, one case developed avascular necrosis (AVN)
      and screw cutout, but satisfactory outcomes were obtained after removal of
      implant. Besides, varus displacement occurred in one case, the patient acquired
      good function without revision. There were no infection, bone nonunion, and
      hardware-related complications occurred in any case. CONCLUSIONS: Both anatomical
      allograft and fibula shaft with LCPs showed relatively good clinical outcomes for
      elderly patients with four-part PHF.

PMID- 26195026
TI  - Education and Imaging. Gastrointestinal: Covered duodenal metal stent fracture
      and its removal with "lasso" technique.

PMID- 26195027
TI  - Comparison of multi-recognition molecularly imprinted polymers for recognition of
      melamine, cyromazine, triamterene, and trimethoprim.
AB  - Three fragmental templates, including 2,4-diamino-6-methyl-1,3,5-triazine (DMT),
      cyromazine (CYR), and trimethoprim (TME), were used to prepare the fragment
      molecularly imprinted polymers (FMIPs), respectively, in polar ternary porogen
      which was composed of ionic liquid ([BMIM]BF4), methanol, and water. The
      morphology, specific surface areas, and selectivity of the obtained FMIPs for
      fragmental analogues were systematically characterized. The experimental results
      showed that the FMIPs possessed the best specific recognition ability to the
      relative template and the greatest imprinting factor (IF) was 5.25, 6.69, and
      7.11 of DMT on DMT-MIPs, CYR on CYR-MIPs, and TME on TME-MIPs, respectively. In
      addition, DMT-MIPs also showed excellent recognition capability for fragmental
      analogues including CYR, melamine (MEL), triamterene (TAT), and TME, and the IFs
      were 2.08, 3.89, 2.18, and 2.60, respectively. The effects of pH and temperature
      on the retention of the fragmental and structural analogues were studied in
      detail. Van't Hoff analysis indicated that the retention and selectivity on FMIPs
      were an entropy-driven process, i.e., steric interaction. The resulting DMT-MIPs
      were used as a solid-phase extraction material to enrich CYR, MEL, TAT, and TME
      in different bio-matrix samples for high-performance liquid chromatography
      analysis. The developed method had acceptable recoveries (86.8-98.6%, n = 3) and
      precision (2.7-4.6%) at three spiked levels (0.05-0.5 MUg g(-1)).

PMID- 26195028
TI  - Identification of species' blood by attenuated total reflection (ATR) Fourier
      transform infrared (FT-IR) spectroscopy.
AB  - Blood is one of the most common and informative forms of biological evidence
      found at a crime scene. A very crucial step in forensic investigations is
      identifying a blood stain's origin. The standard methods currently employed for
      analyzing blood are destructive to the sample and time-consuming. In this study,
      attenuated total reflection (ATR) Fourier transform infrared (FT-IR) spectroscopy
      is used as a confirmatory, nondestructive, and rapid method for distinction
      between human and animal (nonhuman) blood. Partial least squares-discriminant
      analysis (PLS-DA) models were built and demonstrated complete separation between
      human and animal donors, as well as distinction between three separate species:
      human, cat, and dog. Classification predictions of unknown blood donors were
      performed by the model, resulting in 100 % accuracy. This study demonstrates ATR
      FT-IR spectroscopy's great potential for blood stain analysis and species
      discrimination, both in the lab and at a crime scene since portable ATR FT-IR
      instrumentation is commercially available. 

PMID- 26195029
TI  - Family matters? The effect of kinship care on foster care disruption rates.
AB  - Compared with other types of out-of-home care, kinship care is cheap, and offers
      the child a more familiar environment. However, little is known about the causal
      effect of kinship care on important outcomes. This study is the first to estimate
      causal effects of kinship care on placement stability, using full-sample
      administrative data (N=13,157) and instrumental variables methods. Results show
      that, in a sample of children of age 0-17 years, kinship care is as stable as
      other types of care, and only when the kin caregiver is particularly empathic and
      dutiful does this type of care prove more stable. Thus, in terms of stability,
      most children do not benefit additionally from being placed with kin. 

PMID- 26195030
TI  - Molecular phylogeny of the subfamily Stevardiinae Gill, 1858 (Characiformes:
      Characidae): classification and the evolution of reproductive traits.
AB  - BACKGROUND: The subfamily Stevardiinae is a diverse and widely distributed clade
      of freshwater fishes from South and Central America, commonly known as "tetras"
      (Characidae). The group was named "clade A" when first proposed as a monophyletic
      unit of Characidae and later designated as a subfamily. Stevardiinae includes 48
      genera and around 310 valid species with many species presenting inseminating
      reproductive strategy. No global hypothesis of relationships is available for
      this group and currently many genera are listed as incertae sedis or are
      suspected to be non-monophyletic. RESULTS: We present a molecular phylogeny with
      the largest number of stevardiine species analyzed so far, including 355 samples
      representing 153 putative species distributed in 32 genera, to test the group's
      monophyly and internal relationships. The phylogeny was inferred using DNA
      sequence data from seven gene fragments (mtDNA: 12S, 16S and COI; nuclear: RAG1,
      RAG2, MYH6 and PTR). The results support the Stevardiinae as a monophyletic group
      and a detailed hypothesis of the internal relationships for this subfamily.
      CONCLUSIONS: A revised classification based on the molecular phylogeny is
      proposed that includes seven tribes and also defines monophyletic genera,
      including a resurrected genus Eretmobrycon, and new definitions for Diapoma,
      Hemibrycon, Bryconamericus sensu stricto, and Knodus sensu stricto, placing some
      small genera as junior synonyms. Inseminating species are distributed in several
      clades suggesting that reproductive strategy is evolutionarily labile in this
      group of fishes.

PMID- 26195031
TI  - Correlating preoperative imaging with intraoperative fluoroscopy in iliosacral
      screw placement.
AB  - BACKGROUND: Percutaneous iliosacral screw placement can successfully stabilize
      unstable posterior pelvic ring injuries. Intraoperative fluoroscopic imaging is a
      vital component needed in safely placing iliosacral screws. Obtaining and
      appropriately interpreting fluoroscopic views can be challenging in certain
      clinical scenarios. We report on a series of patients to demonstrate how
      preoperative computed tomography (CT) imaging can be used to anticipate the
      appropriate intraoperative inlet and outlet fluoroscopic views. MATERIALS AND
      METHODS: 24 patients were retrospectively identified with unstable pelvic ring
      injuries requiring operative fixation using percutaneous iliosacral screws.
      Utilizing the sagittal reconstructions of the preoperative CT scans, anticipated
      inlet and outlet angle measurements were calculated. The operative reports were
      reviewed to determine the angles used intraoperatively. Postoperative CT scans
      were reviewed for repeat measurements and to determine the location and safety of
      each screw. RESULTS: Preoperative CT scans showed an average inlet of 20.5
      degrees  (7 degrees -37 degrees ) and an average outlet of 42.8 degrees  (30
      degrees -59 degrees ). Intraoperative views showed an average inlet of 24.9
      degrees  (12 degrees -38 degrees ) and an average outlet of 42.4 degrees  (29
      degrees -52 degrees ). Postoperative CT scans showed an average inlet of 19.4
      degrees  (8 degrees -31 degrees ) and an average outlet of 43.2 degrees  (31
      degrees -56 degrees ). The average difference from preoperative to intraoperative
      was 4.4 degrees  (-21 degrees  to 5 degrees ) for the inlet and 0.45 degrees  (-9
      degrees  to 7 degrees ) for the outlet. The average difference between the
      preoperative and postoperative CT was 2.04 degrees  (0 degrees -6 degrees ) for
      the inlet and 2.54 degrees  (0 degrees -7 degrees ) for the outlet. CONCLUSION:
      There is significant anatomic variation of the posterior pelvic ring. The
      preoperative CT sagittal reconstruction images allow for appropriate preoperative
      planning for anticipated intraoperative fluoroscopic inlet and outlet views
      within 5 degrees . Having knowledge of the desired intraoperative views
      preoperatively prepares the surgeon, aids in efficiently obtaining correct
      intraoperative views, and ultimately assists in safe iliosacral screw placement.

PMID- 26195032
TI  - [Cutaneous symptoms of various vasculitides].
AB  - The skin is one of the organs most frequently involved in vasculitides. Cutaneous
      vasculitis may present (1) part of a systemic vasculitis (e.g., IgA vasculitis),
      (2) a skin-restricted or skin-dominant variant of the corresponding systemic
      vasculitis without clinically apparent visceral involvement (e.g., cutaneous IgA
      vasculitis), or (3) a vasculitis occurring exclusively in the skin (e.g.,
      erythema elevatun diutinum). The clinical symptoms of vasculitides are markedly
      determined by the size of the predominantly affected blood vessels. Systemic
      polyarteritis nodosa is regarded as a medium vessel vasculitis and is associated
      with multiple skin symptoms: (1) vasculitis of digital arteries with ensuing
      digital infarction, (2) livedo racemosa and subcutaneous nodules, and (3) in some
      patients even purpura and hemorrhagic macules due to additional small vessel
      vasculitis. In contrast, in its skin-restricted entity (i.e., cutaneous
      polyarteritis nodosa), the predominant symptoms are subcutaneous nodules
      surrounded by livedo racemosa, often on the lower legs. Among small-vessel
      vasculitides palpable purpura with predilection for the legs is a nearly
      pathognomonic feature of immune complex vasculitis. Variations in clinical
      symptoms indicate additional pathophysiological mechanisms or different
      vascultides: (1) ANCA-associated vasculitides often also entail nodules or
      sometimes livedo, (2) cryoglobulinemic vasculitis additionally may present with
      necrosis at cold exposed areas and involvement of vessels of various size, (3)
      small vessel vasculitis associated with systemic lupus erythematosus or
      rheumatoid arthritis shows predilection for additional sites (e.g., nailfolds)
      and also involvement of vessels beyond postcapillary venules, (4) recurrent
      macular vasculitis in hypergammaglobulinemia also occurs on dependent parts, but
      shows numerous small hemorrhagic macules instead of palpable purpura, (5)
      erythema elevatum diutinum begins with brightly red to violaceous plaques at
      extensor sites, followed by fibrotic nodules. Consequently, cutaneous symptoms
      provide pivotal clues for further diagnosis and ensuing management of
      vasculitides.

PMID- 26195033
TI  - All-carbon based graphene field effect transistor with graphitic electrodes
      fabricated by e-beam direct writing on PMMA.
AB  - A so called all-carbon based graphene field effect transistor (GFET) in which the
      electrodes are composed of graphite-like nano-sheets instead of metals in the
      traditional devices is fabricated by one-step e-beam direct writing (EBDW). It is
      also found that the graphite-like nano-sheets in electrodes are perpendicular to
      the channel graphene, which is confirmed by the transmission electron microscopy
      (HRTEM). The one-step fabrication of the carbonaceous electrodes is more
      convenient and lower-cost comparing to the preparation of traditional metal
      electrodes and can be applied to many other nano-electronic devices. 

PMID- 26195034
TI  - Development of an achiral supercritical fluid chromatography method with
      ultraviolet absorbance and mass spectrometric detection for impurity profiling of
      drug candidates. Part I: Optimization of mobile phase composition.
AB  - Supercritical fluid chromatography (SFC) is a very useful tool in the purpose of
      impurity profiling of drug candidates, as an adequate selection of stationary
      phases can provide orthogonal separations so as to maximize the chances to see
      all impurities. The purpose of the present work is to develop a method for
      chemical purity assessment. The first part, presented here, focuses on mobile
      phase selection to ensure adequate elution and detection of drug-like molecules,
      while the second part focuses on stationary phase selection for optimal
      separation and orthogonality. The use of additives in the carbon dioxide -
      solvent mobile phase in SFC is now commonplace, and enables in particular to
      increase the number of eluted compounds and to improve peak shapes. The objective
      of this first part was to test different additives (acids, bases, salts and
      water) for their chromatographic performance assessed in gradient elution with a
      diode-array detector, but also for the mass responses obtained with a single
      quadrupole mass detector, equipped with an electrospray ionization source (Waters
      ACQUITY QDa). In this project, we used a selection of one hundred and sixty
      compounds issued from Servier Research Laboratories to screen a set of columns
      and additives in SFC with a Waters ACQUITY UPC(2) system. The selected columns
      were all high-performance columns (1.7-1.8MUm with totally porous particles or
      2.6-2.7MUm with superficially porous particles) with a variety of stationary
      phase chemistries. Initially, eight additives dissolved in the methanol co
      solvent were tested on a UPC(2) ACQUITY UPC(2) HSS C18 SB column. A Derringer
      desirability function was used to classify the additives according to selected
      criteria: elution capability, peak shapes, UV baseline drift, and UV and mass
      responses (signal-to-noise ratios). Following these tests, the two best additives
      (ammonium acetate and ammonium hydroxide) were tested on a larger number of
      columns (10) where the two additives appeared to provide very comparable overall
      scores. However, ammonium acetate was selected for slightly better
      chromatographic quality. In a second step, we investigated the effects of
      ammonium acetate concentration (between 0 and 25mM in the methanol co-solvent) on
      retention and peak efficiency. Two types of silica supports were tested by
      working with ACQUITY UPC(2) HSS C18 SB and BEH columns. 20mM ammonium acetate in
      methanol with 2% water was finally selected as the best co-solvent composition. 

PMID- 26195035
TI  - Evaluation of steroidomics by liquid chromatography hyphenated to mass
      spectrometry as a powerful analytical strategy for measuring human steroid
      perturbations.
AB  - This review presents the evolution of steroid analytical techniques, including
      gas chromatography coupled to mass spectrometry (GC-MS), immunoassay (IA) and
      targeted liquid chromatography coupled to mass spectrometry (LC-MS), and it
      evaluates the potential of extended steroid profiles by a metabolomics-based
      approach, namely steroidomics. Steroids regulate essential biological functions
      including growth and reproduction, and perturbations of the steroid homeostasis
      can generate serious physiological issues; therefore, specific and sensitive
      methods have been developed to measure steroid concentrations. GC-MS measuring
      several steroids simultaneously was considered the first historical standard
      method for analysis. Steroids were then quantified by immunoassay, allowing a
      higher throughput; however, major drawbacks included the measurement of a single
      compound instead of a panel and cross-reactivity reactions. Targeted LC-MS
      methods with selected reaction monitoring (SRM) were then introduced for
      quantifying a small steroid subset without the problems of cross-reactivity. The
      next step was the integration of metabolomic approaches in the context of steroid
      analyses. As metabolomics tends to identify and quantify all the metabolites
      (i.e., the metabolome) in a specific system, appropriate strategies were proposed
      for discovering new biomarkers. Steroidomics, defined as the untargeted analysis
      of the steroid content in a sample, was implemented in several fields, including
      doping analysis, clinical studies, in vivo or in vitro toxicology assays, and
      more. This review discusses the current analytical methods for assessing steroid
      changes and compares them to steroidomics. Steroids, their pathways, their
      implications in diseases and the biological matrices in which they are analysed
      will first be described. Then, the different analytical strategies will be
      presented with a focus on their ability to obtain relevant information on the
      steroid pattern. The future technical requirements for improving steroid analysis
      will also be presented. 

PMID- 26195036
TI  - Development of an achiral supercritical fluid chromatography method with
      ultraviolet absorbance and mass spectrometric detection for impurity profiling of
      drug candidates. Part II. Selection of an orthogonal set of stationary phases.
AB  - Impurity profiling of organic products that are synthesized as possible drug
      candidates requires complementary analytical methods to ensure that all
      impurities are identified. Supercritical fluid chromatography (SFC) is a very
      useful tool to achieve this objective, as an adequate selection of stationary
      phases can provide orthogonal separations so as to maximize the chances to see
      all impurities. In this series of papers, we have developed a method for achiral
      SFC-MS profiling of drug candidates, based on a selection of 160 analytes issued
      from Servier Research Laboratories. In the first part of this study, focusing on
      mobile phase selection, a gradient elution with carbon dioxide and methanol
      comprising 2% water and 20mM ammonium acetate proved to be the best in terms of
      chromatographic performance, while also providing good MS response [1]. The
      objective of this second part was the selection of an orthogonal set of ultra
      high performance stationary phases, that was carried out in two steps. Firstly, a
      reduced set of analytes (20) was used to screen 23 columns. The columns selected
      were all 1.7-2.5MUm fully porous or 2.6-2.7MUm superficially porous particles,
      with a variety of stationary phase chemistries. Derringer desirability functions
      were used to rank the columns according to retention window, column efficiency
      evaluated with peak width of selected analytes, and the proportion of analytes
      successfully eluted with good peak shapes. The columns providing the worst
      performances were thus eliminated and a shorter selection of columns (11) was
      obtained. Secondly, based on 160 tested analytes, the 11 columns were ranked
      again. The retention data obtained on these columns were then compared to define
      a reduced set of the best columns providing the greatest orthogonality, to
      maximize the chances to see all impurities within a limited number of runs. Two
      high-performance columns were thus selected: ACQUITY UPC(2) HSS C18 SB and
      Nucleoshell HILIC. 

PMID- 26195037
TI  - Exploring the potentialities of an improved ultrasound-assisted quick, easy,
      cheap, effective, rugged, and safe-based extraction technique combined with
      ultrahigh pressure liquid chromatography-fluorescence detection for determination
      of Zearalenone in cereals.
AB  - Zearalenone (ZEA), a secondary metabolite from Fusarium graminearum fungi that
      invade crops and grow during blooming in moist cool field conditions, is a
      nonsteroidal oestrogen, biologically very potent, although hardly toxic.
      Different analytical methods, among which a quick, easy, cheap, effective,
      rugged, and safe (QuEChERS) strategy, combined with or liquid chromatography,
      have been proposed for ZEA determination in foods. However, this extraction
      procedure has the disadvantage of using large amount of organic solvents,
      partitioning salts and sample volume, which limits the technique application on
      the fields where the sample amount is critical. Therefore in this work an
      improved sample preparation step based on the original QuEChERS (O-QuEChERS)
      approach, the MU-QuEChERS, combined with ultrasound-assisted extraction (USAE)
      and ultrahigh pressure liquid chromatography (UHPLC) analysis with fluorescence
      detection (FLR) is proposed for the sensitive and high-throughput quantification
      of ZEA in cereals. The proposed analytical strategy, MU-QuEChERSUSAE, uses up to
      32 times lower amounts of partitioning salts, lower sample amount and lower
      extraction solvents, in comparison with O-QuEChERS technique. The performance of
      the analytical approach was assessed by studying the selectivity, specificity,
      limits of detection and quantification, linear dynamic range, matrix effect and
      precision. Good linearity (r(2)>0.99) was achieved for ZEA, and limits of
      detection (LOD=3.4MUgkg(-1)) and limits of quantification (LOQ=4.7MUgkg(-1)) were
      found below the tolerance levels set by European Commission. Good recoveries were
      obtained with different spiked concentrations, ranged from 80.2% to 109.7%, with
      relative standard deviations (RSD) lower than 5.0%. The comparison of the
      analytical performance of the proposed MU-QuEChERSUSAE with O-QuEChERS showed the
      powerful ability of the proposed strategy since it gives comparable results but
      using lower amounts of sample, partitioning salts and volume of the organic
      solvent, revealing of great potential and improvement of the proposed method. 

PMID- 26195038
TI  - Polypropylene membrane coated with carbon nanotubes functionalized with chitosan:
      Application in the microextraction of polychlorinated biphenyls and
      polybrominated diphenyl ethers from environmental water samples.
AB  - Acid oxidized multi-walled carbon nanotubes (CNTs) functionalized with chitosan
      were coated on polypropylene membrane and used as sorbent to extract trace
      polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) from
      environmental water samples. The analytes were extracted by the hydrophobic
      interaction between analytes and the functionalized CNTs. The chitosan polymer
      coating also contributed to extraction efficiency. Microextraction conditions
      (different types of desorption solvent, extraction time, salt concentration,
      stirring rate and desorption time) were optimized by means of orthogonal array
      design (OAD). A mixed level OAD matrix, OA16 (4(1)*2(12)) was employed for the
      initial optimization. Based on the results of the first step, n-hexane was chosen
      as desorption solvent and 5min was selected as desorption time. Extraction time,
      stirring rate and salt concentration were further optimized in the second step by
      an OA16 (4(5)) matrix. Under the optimized conditions, calibration curves with
      coefficients of determination higher than 0.993 over the concentration range of
      0.2 and 50ng/ml. Low limits of detection (<0.60ng/l) and acceptable
      reproducibility with relative standard deviations in the range of 0.17% and
      5.01%, were achieved. The developed method was applied to extract PCBs and PBDEs
      from environmental water samples. The relative recoveries of the analytes spiked
      into the real water samples ranged from 85.6 to 104.1% at 0.2ng/ml of each
      analyte, and from 82.4 to 98.6% at 2ng/ml of each analyte. 

PMID- 26195039
TI  - Ion-pair reversed phase liquid chromatography with ultraviolet detection for
      analysis of ultraviolet transparent cations.
AB  - This paper describes the use of an anionic ion-pair reagent (IPR) to impove the
      ultraviolet (UV) detection and hydrophobic retention of polar and UV transparent
      cations. Anionic IPR added to the mobile phase forms an ion-pair with cations.
      Formation of the ion-pair causes a redshift in the absorption wavength, making it
      possible for direct UV detection of UV-inactive cations. The ion-pairs with
      increased hydrophobicity were separated by reversed phase liquid chromatography
      (RPLC). Different perfluorinated caboxylic acids (trifluoroacetic acid,
      heptafluorobutyric acid, nonafluoropentanoic acid) were evaluted as IPR in the
      separation and detection of the common cations sodium, ammonium and
      Tris(hydroxymethyl)aminomethane (Tris). The effects of the IPR type and
      concentration on separation and detection have been investigated to understand
      the separation and detection mechanisms. The optimal separation and detection
      condtions were attained with mobile phase containing 0.1% nonafluoropentanoic
      acid and with the UV detection at 210nm. UV detection and charged aerosol
      detection (CAD) were compared in the quantitation of the cations. The limit of
      quantitation (LOQ) of sodium and Tris with UV detection is comparable to that by
      CAD. The LOQ of ammonium with UV detection (1ppm or 3ng) is about 20-fold lower
      than that (20ppm or 60ng) by CAD. The RPLC-UV method was used to monitor ammonium
      clearance during ultrafiltration and diafiltration in the manfucaturing of
      biopharmceutical drug substance. 

PMID- 26195041
TI  - A contamination-insensitive probe for imaging specific biomolecules by secondary
      ion mass spectrometry.
AB  - Imaging techniques should differentiate between specific signals, from the
      biomolecules of interest, and non-specific signals, from the background. We
      present a probe containing (15)N and (14)N isotopes in approximately equal
      proportion, for secondary ion mass spectrometry imaging. This probe designed for
      a precise biomolecule analysis is insensitive to background signals. 

PMID- 26195042
TI  - Abstracts of the 13th International Congress of the European Association for
      Veterinary Pharmacology and Toxicology (EAVPT 2015), 19-22 July, Nantes, France.

PMID- 26195040
TI  - Active suppression of intestinal CD4(+)TCRalphabeta(+) T-lymphocyte maturation
      during the postnatal period.
AB  - Priming of the mucosal immune system during the postnatal period substantially
      influences host-microbial interaction and susceptibility to immune-mediated
      diseases in adult life. The underlying mechanisms are ill defined. Here we show
      that shortly after birth, CD4 T cells populate preformed lymphoid structures in
      the small intestine and quickly acquire a distinct transcriptional profile. T
      cell recruitment is independent of microbial colonization and innate or adaptive
      immune stimulation but requires beta7 integrin expression. Surprisingly, neonatal
      CD4 T cells remain immature throughout the postnatal period under homeostatic
      conditions but undergo maturation and gain effector function on barrier
      disruption. Maternal SIgA and regulatory T cells act in concert to prevent immune
      stimulation and maintain the immature phenotype of CD4 T cells in the postnatal
      intestine during homeostasis. Active suppression of CD4 T-cell maturation during
      the postnatal period might contribute to prevent auto-reactivity, sustain a broad
      TCR repertoire and establish life-long immune homeostasis. 

PMID- 26195043
TI  - Confirmation of TTC8 as a disease gene for nonsyndromic autosomal recessive
      retinitis pigmentosa (RP51).
AB  - Nonsyndromic retinitis pigmentosa (RP) is genetically highly heterogeneous, with
      >100 disease genes identified. However, mutations in these genes explain only 60%
      of all RP cases. Blood samples were collected from 12 members of an autosomal
      recessive RP family. Whole genome homozygosity mapping and haplotype analysis
      placed the RP locus in this family at chromosome 14q31.3. Whole-exome sequencing
      (WES) in proband revealed a mutation in TTC8, which was flagged as most likely
      candidate gene by bioinformatic analysis. TTC8 is mutated in Bardet-Biedl
      syndrome 8 (BBS8), and once reported previously in a family with nonsyndromic RP.
      Sequencing of amplified products of exon 13 of TTC8 validated c.1347G>C
      (p.Gln449His), a novel change that affects the final nucleotide of exon 13 and
      might deleteriously affect splicing. This mutation segregated completely with the
      disease in the family and was not observed in 100 ethnically matched controls
      from same population. This represents second report of a TTC8 mutation in
      nonsyndromic RP, thus confirming the identity of TTC8 as causative gene for RP51.

PMID- 26195044
TI  - The effect of menarche age, parity and lactation on bone mineral density in
      premenopausal ambulatory multiple sclerosis patients.
AB  - Although pregnancy and breast-feeding do not have any deleterious effect on
      disease activity in female multiple sclerosis (MS) patients, their role on bone
      mineral density (BMD) and osteoporosis risk is unknown. We investigated the role
      of age at menarche, parity and lactation on BMD expressed as percentage of the
      mean BMD (%BMD) in 46 pre-menopausal ambulatory female MS patients using dual
      energy X-ray absorptiometry (DXA) scans in lumbar spine (LS) and hip. MS female
      patients with age at menarche >=13 years old had reduced %BMD compared to those
      with menarche age <13 years (95.2+/-10.7 vs 102.1+/-13.3, p=0.05 in LS; 90.5+/
      12.6 vs 99.8+/-12.6, p=0.02 in hip). Parity did not result in any statistically
      significant changes in either LS or hip. Patients that breastfed their offspring
      compared to those that did not had significantly lower BMD in both LS (93.9+/-9.3
      vs 110.7+/-15.6, p=0.004) and hip (91.6+/-10.7 vs 105.6+/-15.3, p=0.02). MS
      female patients with menarche at age>=13 years and those who breastfed their
      offspring may have reduced BMD. Larger studies are needed to verify these
      findings and establish a definite role of menarche age and breast feeding with
      BMD. 

PMID- 26195045
TI  - Neurologists' accuracy in predicting cognitive impairment in multiple sclerosis.
AB  - Cognitive impairment affects approximately 40-70% of MS patients. As management
      of MS typically begins with, and is co-ordinated by neurologists, they are often
      the first to raise concerns about a patient's cognitive functioning. However, it
      is not known how accurate the neurological examination is in identifying
      cognitive impairment. To this end, we conducted a retrospective chart review of
      97 MS patients referred by neurologists for neuropsychological assessment based
      on suspected cognitive impairment. Patients were classified as globally-impaired
      or intact according to failure on 2 or more of 11 cognitive indices comprising
      the MACFIMS, a recommended neuropsychological battery for MS. Neurologists'
      accuracy was not significantly different from chance, Chi(2)=1.25, p=0.26, with
      44.3% of patients with suspected cognitive impairment showing global impairment
      on objective testing. Cognitively intact patients when compared to those who were
      impaired had higher levels of education and were less likely to have mood
      disturbances. These findings indicate the clinical interview and standard
      neurological examination are not sufficiently sensitive to detect cognitive
      impairment in MS, and suggest the need for a brief, accurate cognitive screen to
      complement routine clinical evaluation.

PMID- 26195046
TI  - Health care utilization before and after intensive care unit admission in
      multiple sclerosis.
AB  - OBJECTIVES: The incidence of intensive care unit (ICU) admission is elevated in
      the multiple sclerosis (MS) population but the reasons for this are incompletely
      understood, as are outcomes post-ICU admission. Among MS patients we examined the
      association between ICU admission and health care utilization in the year
      preceding admission, and compared health care utilization following ICU admission
      among persons with MS and persons from the general population. METHODS: We used
      population-based administrative data from Manitoba, Canada to identify 4237 MS
      cases of which 2547 were incident. We compared the incidence rates of ICU
      admission in the prevalent MS population according to health care utilization in
      the year before admission, adjusting for age, sex, comorbidity and socioeconomic
      status. Among incident cases of MS we compared rates of health care utilization
      after ICU admission to those in a matched general population cohort. We used
      generalized linear models adjusting for age, sex, socioeconomic status, region,
      comorbidity and utilization before admission. RESULTS: Of 4219 prevalent MS
      cases, 222 (5.3%) were admitted to the ICU. After adjustment, any hospitalization
      in the prior year conferred an 80% increased incidence, and physician visits in
      the highest tertile and prescription costs in the highest quartile in the prior
      year each conferred a more than two-fold increased incidence of admission. Among
      2547 incident cases of MS, 109 (4.3%) were admitted to the ICU and 93 survived
      their admission. Thirty-eight percent of the MS population were re-hospitalized
      in the year following admission, similar to the matched population (33.8%). Seven
      percent of both populations were readmitted to the ICU. The MS population had
      more hospital days after ICU admission than the matched population (adjusted RR
      3.11; 95% CI: 1.34-5.90). After adjustment the number of physician visits did not
      differ between populations. CONCLUSIONS: The incidence of ICU admission is higher
      among persons with MS who have higher prior health care utilization. Health care
      utilization remains high after ICU admission. Efforts to prevent ICU admission in
      this population are needed.

PMID- 26195047
TI  - Relation of quantitative visual and neurologic outcomes to fatigue in multiple
      sclerosis.
AB  - BACKGROUND: The relation of fatigue in multiple sclerosis (MS) to the visual
      system, an emerging structural and functional surrogate in MS, has not been well
      established. OBJECTIVE: We examined how physical and cognitive fatigue could be
      associated with visual dysfunction and neurologic impairment. METHODS: At a
      single time-point, we assessed 143 patients with: Low-contrast letter acuity
      (LCLA) and high-contrast visual acuity (VA) testing, the 25-Item National Eye
      Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Neuro-Ophthalmic
      Supplement, the Modified Fatigue Impact Scale (MFIS), the MS Functional Composite
      (MSFC), and the Expanded Disability Status Scale (EDSS). RESULTS: Worse binocular
      LCLA scores were associated with increased levels of total and physical fatigue
      (p<=0.026). Greater levels of fatigue were also associated with reduced vision
      specific QOL (p<0.001). Patients with more physical, but not cognitive, fatigue
      had greater levels of impairment by the Timed 25-Foot Walk (T25W, r=0.39,
      p<0.001), 9-Hole Peg Test (9HP r=0.22, p=0.011) and EDSS (r=0.45, p<0.001).
      CONCLUSIONS: Reduced vision in MS is highly associated with physical fatigue and
      could be used to capture more global, difficult to describe, symptoms. The
      potential differences in physical vs. cognitive fatigue and their correlates may
      begin to provide insight into their underlying mechanisms.

PMID- 26195048
TI  - CLIPPERS syndrome: Case report in a Brazilian patient with a long term disease
      evolution.
AB  - INTRODUCTION: Chronic Lymphocytic Inflammation with Pontine Perivascular
      Enhancement Responsive to Steroids (CLIPPERS Syndrome) was first described in
      2010. Since then, about 50 cases have been reported around the world, but none in
      Portuguese-speaking countries. We report a case of patient of the Neurological
      Rehabilitation ward of Sarah Hospital/Brasilia, with clinical and radiologic
      features compatible with CLIPPERS Syndrome. The diagnosis was made only after
      fourteen years of symptoms onset. CASE REPORT: 49-year-old male, presenting with
      progressive pancerebellar syndrome followed by spastic paraplegia with neurogenic
      bladder and progressive worsening over 14 years. The radiological response to
      steroid was suggestive of CLIPPERS Syndrome, however it was not accompanied by
      significant clinical improvement. CONCLUSION: This is the first described case in
      Brazil,and this pattern of progression suggests that CLIPPERS is a degenerative
      disease. Its relevance must be acknowledged for being an important differential
      diagnosis of multiple sclerosis and other demyelinating diseases. Early diagnosis
      may be critical to halt the progression and affect outcome of the disease.

PMID- 26195049
TI  - Occupational stress and personality traits in multiple sclerosis: A preliminary
      study.
AB  - Multiple Sclerosis (MS) is a demyelinating and neurodegenerative disease of the
      central nervous system, causing a wide range of neurological and psychological
      symptoms. Impairment of ambulation and cognition in particular are associated
      with work difficulties and unemployment. Although many aspects of work status
      have been investigated in MS, there are no reports on factors that predict the
      development of occupational stress, prior to job loss. The aim of this
      preliminary study was to ascertain if personality traits predispose MS patients
      to occupational stress. We evaluated 26 MS patients using physical disability
      scales and self-report questionnaires focused on mood, fatigue, and personality
      [measured with the NEO Five Factor Inventory]. The primary outcome measure was
      the Occupational Stress Indicator [OSI]. Results showed significant positive
      correlations (p<.05) between high neuroticism, and occupational stress.
      Conversely, low extraversion and conscientiousness were also associated with job
      stress. The direction of these correlations was consistent with prior research
      showing that high neuroticism, and low extraversion and conscientiousness, are
      risk factors for MS disease severity as evidenced by brain atrophy, cognitive
      impairment and adaptation in MS. We are developing interventions to help patients
      cope with these maladaptive personality dispositions in the hope that employment
      may be maintained. 

PMID- 26195050
TI  - Clinical decision-making in multiple sclerosis: Challenges reported
      internationally with emerging treatment complexity.
AB  - INTRODUCTION: The introduction of several new disease-modifying therapies (DMTs)
      to the field of Multiple Sclerosis (MS) treatment requires that MS healthcare
      providers have a comprehensive understanding of the implications of each new
      treatment option in order to select the treatment that best suits their patient.
      An international study was conducted in 6 countries to obtain a better
      understanding of the issues and challenges experienced by Neurologists and Nurses
      in the treatment and management of their patients with MS. The goal of this
      research was to obtain evidence to inform future Continuing Medical Education
      (CME) initiatives and health policies that promote knowledge translation to
      clinical practice. This article focuses on challenges reported in relation to the
      use of newly approved therapies, in light of the risks of these new treatments,
      as well as screening and monitoring precautions that must be taken. MATERIALS AND
      METHODS: An exploratory study and literature review informed the design of an IRB
      approved online survey deployed to MS Neurologists and Nurses practicing in 6
      countries (Germany, France, Italy, Spain, UK, USA). RESULTS: The sample consisted
      of actively practicing Neurologists (n=156) and Nurses (n=153). Substantive
      challenges were reported in participant's knowledge of and confidence in three
      categories: i) safety profile of newly approved therapies, ii) screening patients
      for treatment with newly approved therapies, and iii) monitoring for serious
      adverse events. DISCUSSION AND CONCLUSION: Findings indicate that,
      internationally, healthcare providers report substantive challenges integrating
      newly approved therapies into their clinical decision-making. This study
      highlights potential factors underlying the challenges, and identifies important
      targets for CME interventions and policymakers to enhance clinical decision
      making amongst MS providers.

PMID- 26195051
TI  - Is it time to target no evident disease activity (NEDA) in multiple sclerosis?
AB  - The management of multiple sclerosis is becoming increasingly complex with the
      emergence of new and more effective disease-modifying therapies (DMT). We propose
      a new treatment paradigm that individualises treatment based on a choice between
      two interchangeable therapeutic strategies of maintenance-escalation or induction
      therapy. We propose treating- to-target of no evident disease activity (NEDA) as
      defined using clinical and MRI criteria. This algorithm requires active
      monitoring with a rebaselining MRI, at a point in time after the specific DMT
      concerned has had sufficient time to work, and at least annual MRI studies to
      monitor for subclinical relapses. Disease activity on the maintenance-escalation
      therapy arm of the algorithm indicates a sub-optimal treatment response and
      should trigger a discussion about switching, or escalating, therapy or the
      consideration of switching to the induction therapy arm of the algorithm. In
      comparison, disease activity on an induction therapy arm would be an indication
      for retreatment or a switch to the maintenance-escalation therapy arm. We
      envisage the definition of NEDA evolving with time as new technological
      innovations are adopted into clinical practice, for example the normalisation of
      whole, or regional, brain atrophy rates and cerebrospinal fluid neurofilament
      levels. 

PMID- 26195052
TI  - Association between soluble L-selectin and anti-JCV antibodies in natalizumab
      treated relapsing-remitting MS patients.
AB  - OBJECTIVE: In relapsing-remitting MS (RRMS) patients treated with natalizumab,
      the low level of L-selectin-expressing CD4+ T cells has been associated with the
      risk of progressive multifocal leukoencephalopathy (PML). In this study, our aim
      was to correlate the levels of soluble L-selectin and the anti-JCV antibody index
      in the sera of RRMS patients treated with natalizumab. METHODS: This study
      included 99 subjects, including 44 RRMS patients treated with natalizumab, 30
      with interferon beta (IFN-beta) and 25 healthy controls. The levels of soluble L
      selectin (sL-selectin) in sera were measured by ELISA, and the anti-JC Virus
      (JCV) antibody index was determined by the second-generation ELISA (STRATIFY
      JCVTM DxSelectTM) assay. RESULTS: A significant correlation was found between the
      levels of sL-selectin and anti-JCV antibody indices in sera in the natalizumab
      treated patients (r=0.402; p=0.007; n=44), but not in those treated with IFN
      beta. This correlation became even stronger in JCV seropositive patients treated
      with natalizumab for longer than 18 months (r=0.529; p=0.043; n=15). CONCLUSION:
      The results support the hypothesis of sL-selectin being connected to the anti-JCV
      antibody index values and possibly cellular L-selectin. Measurement of serum sL
      selectin should be evaluated further as a potential biomarker for predicting the
      risk of developing PML.

PMID- 26195053
TI  - Effects of dimethyl fumarate on lymphocyte subsets.
AB  - OBJECTIVE: To evaluate changes in absolute lymphocyte counts, lymphocyte subsets,
      and infections in patients treated with dimethyl fumarate (DMF) in comparison to
      the baseline pre-DMF levels. METHODS: A retrospective chart review was conducted
      of 23 MS patients treated with DMF. Absolute lymphocyte counts and lymphocyte
      subsets were obtained at baseline and after at least 3 months of DMF treatment.
      Data on infections requiring medical attention were also collected. RESULTS: A
      total of 23 patients were included in this analysis, 11 male (48%), 12 female
      (52%), with a mean age of 44.5+/-14.1 years, disease duration of 13.7+/-8.9
      years, and EDSS of 3.5+/-1.7. The time between baseline and treatment lymphocyte
      counts was 3.9+/-1.2 months. Significant reductions in absolute lymphocyte counts
      by 35% (p<0.0001), CD3(+) by 34% (p<0.0001), CD4(+) by 34% (p<0.0001), CD8(+) by
      40% (p<0.0001), and CD19(+) counts by 48% (p=0.0098) were found. Grade 2
      lymphopenia occurred in 24% of patients and grade 3 lymphopenia occurred in 1
      patient. Infections occurred in 26% of patients, mainly as urinary tract
      infections (22%) and one fatal case of West Nile encephalitis in a patient with
      grade 3 lymphopenia, who had been on DMF for 5 months. A detailed summary of this
      fatal case is provided. CONCLUSION: Lymphocyte subsets may help to provide better
      understanding of immunologic and safety impact of DMF.

PMID- 26195054
TI  - Muscular dystrophy in a patient with multiple sclerosis. Another "double
      trouble"?
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is considered a relatively common
      muscular dystrophy affecting approximately 1:15,000 individuals in the general
      population. Single case reports have described the rare co-occurrence of FSHD
      with other hereditary neuromuscular disorders, leading to atypical phenotypes. We
      report herein the case of a 26-year-old woman with genetically proven FSHD, who
      additionally developed otherwise typical multiple sclerosis (MS). Although there
      is no direct relationship between FSHD and MS, they might, nevertheless, share
      some common pathophysiological mechanisms, as recent research suggests. In
      particular, we comment on the potential, but not yet proven, role of
      immunological factors in the pathogenesis of FSHD. 

PMID- 26195055
TI  - Specificity and sensitivity of aquaporin 4 antibody detection tests in patients
      with neuromyelitis optica: A meta-analysis.
AB  - OBJECTIVE: Antibodies against water channel protein aquaporin 4 (AQP4) in
      astrocytes play a role in the etiology and physiopathology of neuromyelitis
      optica (NMO); detection of this immunoglobulin in serum is highly suggestive of
      this diagnosis. There are several immunoassays to detect the antibody with
      different sensitivities and specificities. We conducted a meta-analysis to
      determine the overall diagnostic accuracy from these tests. METHODS: We conducted
      a systematic review in five different electronic databases: Pubmed, Embase, The
      Cochrane Library, Scopus, Database of Abstracts of Reviews of Effect (DARE) and
      Lilacs. We included both case control and consecutive enrollment studies that
      evaluated the performance of the immunoassays in patients with suspected NMO in
      comparison with the 2006 Wingerchuk diagnostic criteria. Articles were assessed
      by two different reviewers, who also extracted data. RESULTS: 30 studies for
      three different immunoassays were included in the meta-analysis. To obtain a
      summary estimate for the sensitivity and specificity with 95% confidence interval
      a bivariate random effect model was used. The approximated sensitivity for the
      cell based assay (CBA), the tissue-based assay (TBA) and the ELISA test were
      0.76(95% CI 0.67-0.82), 0.59(95% CI 0.50-0.67), and 0.65(95% CI 0.53-0.75)
      respectively. The mean specificity of the CBA was 0.99 (95% CI 0.97-0.99), TBA
      0.98 (95% CI 0.97-0.99) and ELISA 0.97(95% CI 0.96-0.99). CONCLUSIONS: AQP4
      detection in serum with immunoassay is a great tool for the diagnosis of patients
      with NMO, due to the high specificity, allowing the clinician to differentiate
      this disease from other neurological conditions that resemble NMO.

PMID- 26195056
TI  - Impact of peginterferon beta-1a and disease factors on quality of life in
      multiple sclerosis.
AB  - BACKGROUND: The Phase III ADVANCE study has shown clinical benefits for
      peginterferon beta-1a 125 ug dosed every 2 weeks versus placebo at 1 year in
      patients with relapsing-remitting multiple sclerosis (MS). This study assessed
      the impact of peginterferon beta-1a and disease factors on health-related quality
      of life (HRQoL) using data from ADVANCE. METHODS: HRQoL was assessed at baseline
      and 12, 24, and 48 weeks using the 29-item Multiple Sclerosis Impact Scale (MSIS
      29) and other generic HRQoL measures. Changes in scores from baseline within each
      group and differences in mean change from baseline between groups were evaluated.
      Post-hoc mixed-effects repeated measures analyses were performed to assess the
      impact of confirmed disability progression and relapses, and the interactions of
      treatment and these MS events on HRQoL. Predictors with p>=0.1 were excluded from
      the final models, unless they were clinically meaningful. RESULTS: Relapses and
      confirmed disability progression were major drivers of HRQoL. When comparing week
      48 to baseline, in placebo-treated patients (n=500), confirmed disability
      progression was associated with a 6.0-point worsening (p<0.0001) of MSIS-29
      physical scores, relative to a 1.9-point worsening (p=0.044) with peginterferon
      beta-1a every 2 weeks (n=512). Such findings were observed consistently with
      other generic HRQoL measures. Additionally, having a recent relapse (<=29 days
      before the HRQoL assessment) was associated with a 10.0-point worsening
      (p<0.0001) of MSIS-29 psychological scores in placebo-treated patients, compared
      with a 3.5-point (p=0.031) worsening with peginterferon beta-1a every 2 weeks.
      CONCLUSION: Treatment with peginterferon beta-1a could help to improve or
      maintain HRQoL in addition to clinical outcomes. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00906399.

PMID- 26195057
TI  - Effectiveness of telerehabilitation interventions in persons with multiple
      sclerosis: A systematic review.
AB  - BACKGROUND: Telerehabilitation, a service delivery model using telecommunications
      technology to provide therapy at a distance, is used in persons with multiple
      sclerosis (pwMS), but evidence for their effectiveness is yet to be determined.
      OBJECTIVE: To investigate the effectiveness and safety of telerehabilitation
      intervention pwMS. METHOD: A comprehensive literature search was conducted using
      medical and health science electronic databases. Three reviewers selected
      potential studies and independently assessed the methodological quality. A meta
      analysis was not possible due to heterogeneity amongst included trials, and a
      qualitative analysis was performed for best evidence synthesis. RESULTS: Ten RCTs
      and 2 observational studies (n=564 participants) investigated a wide variety of
      telerehabilitation intervention in pwMS, which included: physical activity;
      educational, behavioural and symptom management programmes. All studies scored
      "low to moderate" on the methodological quality assessment implying high risk of
      bias. Overall, the review found low level evidence for the effectiveness of
      telerehabilitation on reducing short-term disability and reducing and/or
      improving symptoms, such as fatigue. There was low level evidence suggesting some
      benefit of telerehabilitation in improving functional activities; improving
      symptoms in the longer-term; and psychological outcomes and quality of life.
      There is limited data on safety, process evaluation and no data on cost
      effectiveness of telerehabilitation. CONCLUSIONS: A wide range of
      telerehabilitation is used in pwMS, however, the quality of evidence on these
      interventions was low. More robust trials are needed to build evidence about
      these interventions.

PMID- 26195058
TI  - GLACIER: An open-label, randomized, multicenter study to assess the safety and
      tolerability of glatiramer acetate 40 mg three-times weekly versus 20 mg daily in
      patients with relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: The efficacy and safety of glatiramer acetate (GA) 20 mg/mL once
      daily subcutaneous injections (GA20) in relapsing-remitting multiple sclerosis
      (RRMS) is well-established. However, injection-related adverse events (IRAEs) may
      impede treatment adherence and tolerability. GA 40 mg/mL three-times weekly
      (GA40) also has a favorable efficacy and safety profile. OBJECTIVE: To evaluate
      the safety, tolerability, and patient experience when converting from GA20 to
      GA40. METHODS/TRIAL DESIGN: GLACIER was an open-label, randomized, parallel-group
      trial conducted at 31 sites in the US between June 2013 and December 2013. Stable
      RRMS patients on GA20 were randomized in a 1:1 ratio to continue with GA20 or
      convert to GA40. The adjusted mean annualized rate of IRAEs was the primary
      endpoint for this study. Additionally, the severity of IRAEs, rate of injection
      site reactions (ISRs), and patient-reported MS impact and treatment satisfaction
      were compared for the two treatment groups over the 4-month core study. RESULTS:
      A total of 209 patients were randomized to convert to GA40 (n=108) or continue
      with GA20 (n=101). The adjusted mean annualized rate of IRAEs was reduced by 50%
      with GA40 (35.3 events per year; n=108) versus GA20 (70.4 events per year; n=101)
      (risk ratio (RR)=0.50; 95% confidence interval [CI]=0.34-0.74; p=0.0006). There
      was a 60% reduction in the rate of moderate/severe events (GA40 (n=108): 0.9
      events per year versus GA20 (n=101): 2.2 events per year; RR=0.40; p=0.0021).
      Perception of treatment convenience improved for GA40-treated patients soon after
      converting and was sustained. CONCLUSIONS: The GLACIER study demonstrates a
      favorable IRAE and convenience profile of GA40 for RRMS patients. TRIAL
      REGISTRATION: NCT01874145 available at clinicaltrial.gov.

PMID- 26195059
TI  - The effect of dimethyl fumarate (TecfideraTM) on lymphocyte counts: A potential
      contributor to progressive multifocal leukoencephalopathy risk.
AB  - Dimethyl fumarate (TecfideraTM) is an effective therapy for relapsing forms of
      multiple sclerosis (MS). Our study suggests that this drug may have
      immunosuppressive properties evidenced by significant sustained reduction in CD8
      lymphocyte counts and, to a lesser extent, CD4 lymphocyte counts. This
      observation is relevant in light of the recent case of progressive multifocal
      leukoencephalopathy in a patient receiving this drug. 

PMID- 26195060
TI  - Natalizumab is effective in controlling the inflammatory rebound after its
      discontinuation and failure of an alternative treatment.
AB  - Progressive multifocal leukoencephalopathy (PML) is the most feared complication
      when natalizumab (NAT) is used in the treatment of relapsing multiple sclerosis
      (MS). JC virus serologic status is a currently established risk factor for PML.
      When seroconversion occurs, NAT discontinuation should be based on a solid
      rationale to avoid an MS inflammatory resurgence. The JC virus index value may
      also provide further useful information to help practitioners and patients in
      their decision process. 

PMID- 26195061
TI  - Why some of us do not like the expression "no evidence of disease activity"
      (NEDA) in multiple sclerosis.

PMID- 26195062
TI  - Corrigendum to "Cardiovascular autonomic dysfunction in multiple sclerosis: A
      meta-analysis" [Mult. Scler. Relat. Disord. 4 (2015) 104-111].

PMID- 26195063
TI  - Editors' Welcome.

PMID- 26195064
TI  - Cholinergic and serotonergic modulations differentially affect large-scale
      functional networks in the mouse brain.
AB  - Resting-state functional MRI (rsfMRI) is a widely implemented technique used to
      investigate large-scale topology in the human brain during health and disease.
      Studies in mice provide additional advantages, including the possibility to
      flexibly modulate the brain by pharmacological or genetic manipulations in
      combination with high-throughput functional connectivity (FC) investigations.
      Pharmacological modulations that target specific neurotransmitter systems, partly
      mimicking the effect of pathological events, could allow discriminating the
      effect of specific systems on functional network disruptions. The current study
      investigated the effect of cholinergic and serotonergic antagonists on large
      scale brain networks in mice. The cholinergic system is involved in cognitive
      functions and is impaired in, e.g., Alzheimer's disease, while the serotonergic
      system is involved in emotional and introspective functions and is impaired in,
      e.g., Alzheimer's disease, depression and autism. Specific interest goes to the
      default-mode-network (DMN), which is studied extensively in humans and is
      affected in many neurological disorders. The results show that both cholinergic
      and serotonergic antagonists impaired the mouse DMN-like network similarly,
      except that cholinergic modulation additionally affected the retrosplenial
      cortex. This suggests that both neurotransmitter systems are involved in
      maintaining integrity of FC within the DMN-like network in mice. Cholinergic and
      serotonergic modulations also affected other functional networks, however,
      serotonergic modulation impaired the frontal and thalamus networks more
      extensively. In conclusion, this study demonstrates the utility of
      pharmacological rsfMRI in animal models to provide insights into the role of
      specific neurotransmitter systems on functional networks in neurological
      disorders.

PMID- 26195065
TI  - Commentary to "Appraisal of pathogenesis of bladder exstrophy. Proposal of a new
      hypothesis".

PMID- 26195066
TI  - [Hypersensitivity reactions to non-steroidal anti-inflammatory drugs and
      tolerance to alternative drugs].
AB  - INTRODUCTION: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs
      (NSAIDs) are the most common reactions to drugs. The prevalence varies from 0.6
      to 5.7% in general population, but there are no data available in children. The
      aim of this study is to determine the frequency of patients diagnosed with
      hypersensitivity to NSAIDs, and describe their clinical characteristics, type of
      hypersensitivity, and tolerance to alternative drugs. METHODS: Retrospective
      study was conducted on children with suspected hypersensitivity to NSAIDs from
      January 2012 to December 2013. The diagnosis was confirmed by oral drug
      provocation test (DPT) to the drug involved in the group with a history of one
      episode, while in the group with a history of more than one episode with the same
      drug the diagnosis was based on clinical data. Subsequently, a DPT with
      acetylsalicylic acid (ASA) was done in order to classify hypersensitivity into
      selective or multiple. In those cases with a positive result, a DPT was performed
      with alternative drugs. RESULTS: Out of a total of 93 children studied, 26 were
      diagnosed with hypersensitivity to NSAIDs: 7 confirmed by oral DPT, and 19 based
      on clinical data. Multiple hypersensitivity was diagnosed in 50% of patients.
      Ibuprofen was involved in all reactions. The most common clinical manifestation
      was angioedema (44%). Acetaminophen was the best tolerated alternative drug.
      CONCLUSIONS: More than one quarter (28%) of the population studied was diagnosed
      with hypersensitivity to NSAIDs, and 50% had multiple hypersensitivity.
      Acetaminophen is a safe alternative in children with hypersensitivity to NSAIDs.
      Meloxicam may be an alternative in cases that do not tolerate acetaminophen.

PMID- 26195067
TI  - Construction of Anti-CD20 Single-Chain Antibody-CD28-CD137-TCRzeta Recombinant
      Genetic Modified T Cells and its Treatment Effect on B Cell Lymphoma.
AB  - BACKGROUND: Immunotherapy has been explored as a new therapy for B cell lymphoma,
      which is a non-Hodgkin's lymphoma. Because CD20 is a B lymphocyte-specific
      marker, anti-CD20 single chain-tagged T lymphocytes have already begun to be
      experimentally used in B cell lymphoma treatment, but its use is still limited
      because of its unspecific targeting. T cells transfected with CD28 and CD137 can
      significantly improve the ability of cytokines secretion and anti-tumor effect,
      as well as extending T cell survival time and improving their proliferation
      ability. MATERIAL AND METHODS: Genes containing anti-CD20-CD28-CD137-TCRzeta were
      constructed. After cloning and sequencing, the plasmid was constructed and
      packaged by lentivirus. It was transfected to the peripheral blood T lymphocyte
      after identification transfection to induce the fusion protein expression. The
      cells were incubated with Raji cells and the LDH test was performed to detect the
      cytotoxic effect of CAR-T cells; the tumor volume and survival rate were measured
      to observe its inhibitory effect on B cell lymphoma in nude mice. RESULTS: Gene
      with anti-CD20-CD28-CD137-TCRzeta was successfully constructed and transfected to
      the T cell surface. LDH assay revealed that CAR-T cells can kill the Raji cells
      with a killing rate of 32.89+/-6.26%. It can significantly inhibit B cell
      lymphoma growth in nude mice. CONCLUSIONS: T lymphocytes transfected with anti
      CD20-CD28-CD137-TCRzeta fusion gene can kill B cell lymphoma, which could provide
      a new strategy for tumor treatment.

PMID- 26195068
TI  - Neuropathologic correlates of regional brain volumes in a community cohort of
      older adults.
AB  - The objective of this work was 2-fold: to generate macrostructural brain
      signatures of age-related neuropathologies in a community cohort of older adults
      and to determine the contribution of brain macrostructure to the variation in
      antemortem cognition after accounting for the contributions of neuropathologies
      and demographics. Cerebral hemispheres from 165 participants of 2 cohort studies
      of aging were imaged with magnetic resonance imaging ex vivo (mean age at death =
      90 years; standard deviation = 6 years). The volumes of white matter and 42 gray
      matter regions were measured. The same hemispheres also underwent neuropathologic
      examination. Alzheimer's disease pathology was negatively associated with volumes
      of mainly temporal, frontal, and parietal gray matter regions, and with total
      white matter volume (p < 0.05, false discovery rate-corrected). A negative
      association was also detected between hippocampal sclerosis and volumes of the
      hippocampus, as well as other temporal and frontal gray matter regions (p < 0.05,
      false discovery rate-corrected). The volume of mainly medial temporal lobe
      regions explained an additional 5%-6% of the variation in antemortem cognition,
      above and beyond what was explained by neuropathologies and demographics.

PMID- 26195069
TI  - Pancreatic cancer-secreted miR-155 implicates in the conversion from normal
      fibroblasts to cancer-associated fibroblasts.
AB  - Cancer-associated fibroblasts (CAF) are a major constituent of the pancreatic
      cancer microenvironment and that the meaning is as intended. Pancreatic cancer
      cells can induce normal fibroblasts to convert into CAF and, reciprocally, CAF
      promote tumor invasions and proliferations. The mechanism of the conversion from
      normal fibroblasts (NF) to CAF remains unclear. MicroRNA are short non-coding RNA
      involved in the post-transcription gene regulation, which have been defined as an
      imperative controller in tumor invasions, proliferations and colony formations.
      Microvesicles (MV) have been proved to be an important mediator of intercellular
      communication and can selectively transport secreted microRNA from a donor cell
      into a recipient cell. In this study, we isolated primary pancreatic fibroblasts
      from wild type C57 mice and co-cultured them with pancreatic cancer cell lines,
      BxPC-3 and SW1990, and observed the conversion from NF to CAF, or at least CAF
      like cells. This phenomenon could also be replicated in primary fibroblasts
      treated with MV separated from a cancer cell media. We identified that miR-155
      was upregulated in PaC-derived MV and we confirmed that normal fibroblasts could
      convert into CAF after MV containing miR-155 had been taken up. TP53INP1 is a
      target of miR-155 in fibroblasts and a downregulation of TP53INP1 protein levels
      could contribute to the fibroblasts' activation. These results indicated that
      pancreatic cancer cells might reprogram normal adjacent fibroblasts into CAF by
      means of secreted MV containing miR-155. Targeting the circulating microRNA might
      be a potential therapy for malignant tumors. 

PMID- 26195070
TI  - Increased risk of anxiety among patients with urolithiasis: A nationwide
      population-based cohort study.
AB  - OBJECTIVES: To investigate whether patients with urolithiasis are at an increased
      risk of anxiety and depression. METHODS: We used universal insurance claims data
      in Taiwan from 2000 to 2011 to identify patients with newly diagnosed
      urolithiasis (n = 32 617) and those without urolithiasis (n = 130 465).
      Incidences, hazard ratios, and incidence rate ratios of anxiety and depression
      were determined in both cohorts in terms of baseline demographic characteristics
      and comorbidities until December 2011. RESULTS: The urolithiasis cohort yielded a
      higher incidence of anxiety (11.9 vs 6.91 per 1000 person-years) with an adjusted
      hazard ratio of 1.5 (95% confidence interval 1.42-1.57) than the non-urolithiasis
      cohort. The urolithiasis cohort also showed a higher incidence of depression
      (5.79 vs 3.95 per 1000 person-years) with an adjusted hazard ratio of 1.26 (95%
      confidence interval 1.18-1.35) than the non-urolithiasis cohort. Regardless of
      the patients' baseline comorbidities, patients with urolithiasis showed a higher
      incidence rate ratio of anxiety and depression than those without urolithiasis
      (with no comorbidities: adjusted hazard ratio 1.62, 95% confidence interval 1.49
      1.76] for anxiety and adjusted hazard ratio 1.37, 95% confidence interval 1.23
      1.54 for depression). CONCLUSION: Urolithiasis is recurrent, and significantly
      associated with anxiety and depression. Therefore, urologists should diagnose
      patients suspected with this disease and provide proper medical care.

PMID- 26195071
TI  - Development, Optimization, and Characterization of PEGylated Nanoemulsion of
      Prostaglandin E1 for Long Circulation.
AB  - Lipo-PGE1 is the most widely used formulation of PGE1 in clinic. However, PGE1 is
      easier to leak out from lipo-PGE1 and this will lead to the phlebophlogosis when
      intravenous injection. The stability of lipo-PGE1 in storage and in vivo is also
      discounted. The aim of this study is to develop a long-circulating prostaglandin
      E1-loaded nanoemulsion modified with 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG) to improve
      the stability and pharmacokinetics profiles of lipo-PGE1. PEGylated PGE1
      nanoemulsion was prepared using a dispersing-homogenized method. The stability of
      nanoemulsion in 1 month was investigated. Pharmacokinetic studies were employed
      to evaluate the in vivo profile of the optimized nanoemulsion. The optimized
      nanoemulsion PGE1-PEG2000(1%)-NE showed an oil droplet size <100 nm with a
      surface charge of -14 mV. Approximately, 97% of the PGE1 was encapsulated in the
      nanoemulsion. The particle size, zeta potential, and drug loading of PGE1
      PEG2000(1%)-NE were stable in 1 month. After PGE1-PEG2000(1%)-NE was
      intravenously administered to rats, the area under curve (AUC) and half-life of
      PGE1 were, respectively, 1.47-fold and 5.98-fold higher than those of lipo-PGE1
      (commercial formulation). PGE1-PEG2000(1%)-NE was an ideal formulation for
      prolonging the elimination time of PGE1. This novel parenteral colloidal delivery
      system of PGE1 has a promising potential in clinic use.

PMID- 26195072
TI  - Development of Motivate4Change Using the Intervention Mapping Protocol: An
      Interactive Technology Physical Activity and Medication Adherence Promotion
      Program for Hospitalized Heart Failure Patients.
AB  - BACKGROUND: It is important that heart failure (HF) patients adhere to their
      medication regimen and engage in physical activity. Evidence shows that adherence
      to these HF self-management behaviors can be improved with appropriate
      interventions. OBJECTIVE: To further promote medication adherence and physical
      activity among HF patients, we developed an intervention for hospitalized HF
      patients. METHODS: The intervention mapping protocol was applied in the
      development of the intervention. This entailed performing a needs assessment,
      defining change objectives, selecting determinants and strategies, and developing
      the materials. RESULTS: The resulting intervention, Motivate4Change, makes use of
      interactive technology and provides HF patients with personalized feedback and
      advice. Specific change objectives were defined. The relevant behavioral
      determinants for the physical activity program were practical knowledge on
      physical activity performance and self-efficacy for, and perceived benefits of,
      physical activity. For medication-taking, the selected determinants were
      practical knowledge on medication-taking, perceived barriers to medication
      taking, beliefs about the necessity and harm regarding the medication prescribed,
      and beliefs about overprescribing and harm of medication in general. The change
      objectives and behavior change determinants were translated in feedback and
      advice strategies in an interactive technology program that included tailored
      feedback and advice, and role models in videos in which the behaviors and
      overcoming barriers were demonstrated. Relevant stakeholders were involved in the
      interventions development process. The intervention was pretested among HF
      patients and adjustments were made accordingly. CONCLUSIONS: The interactive
      technology physical activity and medication adherence promotion program for
      hospitalized HF patients was systematically developed using the intervention
      mapping protocol and was based on the available theory and evidence regarding HF
      self-management behavior change. The intervention's efficacy is yet to be
      determined in evaluation research.

PMID- 26195073
TI  - Fast and catalyst-free hydrazone ligation via ortho-halo-substituted
      benzaldehydes for protein C-terminal labeling at neutral pH.
AB  - Rapid and catalyst-free hydrazone ligation reaction between ortho
      halobenzaldehyde derivatives and peptide/protein hydrazides was observed at
      neutral pH and room temperature. 2-Chlorobenzaldehyde exhibited the fastest
      reaction and highest conversion rates among the series of ortho
      halobenzaldehydes. The resulting hydrazone-containing bioconjugation products
      were also found to be fairly stable under experimental conditions. The new
      ligation strategy was successfully used for protein C-terminal labeling and
      should provide a practical approach for the modification of proteins. 

PMID- 26195074
TI  - Independent task force unveils five year plan to overhaul cancer services in
      England.

PMID- 26195076
TI  - Automated protein structure determination by NMR.

PMID- 26195075
TI  - Effect of carbamazepine and gabapentin on excitability in the trigeminal
      subnucleus caudalis of neonatal rats using a voltage-sensitive dye imaging
      technique.
AB  - BACKGROUND: The antiepileptic drugs carbamazepine and gabapentin are effective in
      treating neuropathic pain and trigeminal neuralgia. In the present study, to
      analyze the effects of carbamazepine and gabapentin on neuronal excitation in the
      spinal trigeminal subnucleus caudalis (Sp5c) in the medulla oblongata, we
      recorded temporal changes in nociceptive afferent activity in the Sp5c of
      trigeminal nerve-attached brainstem slices of neonatal rats using a voltage
      sensitive dye imaging technique. RESULTS: Electrical stimulation of the
      trigeminal nerve rootlet evoked changes in the fluorescence intensity of dye in
      the Sp5c. The optical signals were composed of two phases, a fast component with
      a sharp peak followed by a long-lasting component with a period of more than 500
      ms. This evoked excitation was not influenced by administration of carbamazepine
      (10, 100 and 1,000 MUM) or gabapentin (1 and 10 MUM), but was increased by
      administration of 100 MUM gabapentin. This evoked excitation was increased
      further in low Mg(2+) (0.8 mM) conditions, and this effect of low Mg(2+)
      concentration was antagonized by 30 MUM DL-2-amino-5-phosphonopentanoic acid
      (AP5), a N-methyl-D-aspartate (NMDA) receptor blocker. The increased excitation
      in low Mg(2+) conditions was also antagonized by carbamazepine (1,000 MUM) and
      gabapentin (100 MUM). CONCLUSION: Carbamazepine and gabapentin did not decrease
      electrically evoked excitation in the Sp5c in control conditions. Further
      excitation in low Mg(2+) conditions was antagonized by the NMDA receptor blocker
      AP5. Carbamazepine and gabapentin had similar effects to AP5 on evoked excitation
      in the Sp5c in low Mg(2+) conditions. Thus, we concluded that carbamazepine and
      gabapentin may act by blocking NMDA receptors in the Sp5c, which contributes to
      its anti-hypersensitivity in neuropathic pain.

PMID- 26195077
TI  - MolProbity for the masses-of data.
AB  - MolProbity is a powerful software program for validating structures of proteins
      and nucleic acids. Although MolProbity includes scripts for batch analysis of
      structures, because these scripts analyze structures one at a time, they are not
      well suited for the validation of a large dataset of structures. We have created
      a version of MolProbity (MolProbity-HTC) that circumvents these limitations and
      takes advantage of a high-throughput computing cluster by using the HTCondor
      software. MolProbity-HTC enables the longitudinal analysis of large sets of
      structures, such as those deposited in the PDB or generated through theoretical
      computation-tasks that would have been extremely time-consuming using previous
      versions of MolProbity. We have used MolProbity-HTC to validate the entire PDB,
      and have developed a new visual chart for the BioMagResBank website that enables
      users to easily ascertain the quality of each model in an NMR ensemble and to
      compare the quality of those models to the rest of the PDB. 

PMID- 26195078
TI  - Selection of distal fusion level in posterior instrumentation and fusion of
      Scheuermann kyphosis: is fusion to sagittal stable vertebra necessary?
AB  - PURPOSE: Distal junctional kyphosis (DJK) is a major instrumentation-related
      complication after the surgical correction of Scheuermann kyphosis (SK). The
      exact criteria to avoid DJK have been controversial. It has been recommended to
      include the SSV into the fusion by some authors, while others suggest that fusion
      to FLV is sufficient. The purpose of this study was to investigate the occurrence
      of DJK in relation to distal fusion level selection in SK surgery by
      investigating the relationship between the sagittal stable vertebra (SSV), first
      lordotic vertebra (FLV), and the lowest instrumented vertebra (LIV). METHODS: 54
      patients (mean age: 21.2 years, range 12-43; male/female: 20/34) with SK who were
      treated by posterior segmental instrumentation and fusion were prospectively
      evaluated. Patients were allocated into 3 groups according to distal fusion
      level. In group 1, SSV was chosen as LIV (n = 20), and in group 2, LIV was the
      FLV (n = 16). Third group consisted of 18 patients in whom SSV and FLV was the
      same vertebra. Distal junctional angle, sagittal plane analysis, and clinical
      outcomes according to SF-36 were evaluated. RESULTS: Mean preoperative kyphosis
      angles were 77.2 degrees , 73.4 degrees , and 76.7 degrees  in groups 1, 2, and
      3, respectively (p = 0.281), which decreased to 38.1 degrees , 37.3 degrees , and
      37.8 degrees  postoperatively at final follow-up (p = 0.988). Mean follow-up time
      was 28.3 months. Correction amounts were similar between the groups (p = 0.409).
      3 patients in SSV group, 5 patients in FLV group, and 3 patients in SSV-FLV group
      developed DJK, which was statistically insignificant. The C7 sagittal plumbline,
      lumbar lordosis, and pelvic parameters were not significantly different before or
      after surgery between the groups. Preoperative and postoperative results of SF-36
      questionnaire were similar in all the groups. None of the patients who had DJK
      required revision surgery during the follow-up time. CONCLUSION: Proper selection
      of distal fusion level is important in order to prevent DJK after SK surgery.
      According to this study, it is not necessary to extend the fusion down to the
      SSV. Fusion to FLV is sufficient and saves a level.

PMID- 26195079
TI  - Cost-utility of minimally invasive versus open transforaminal lumbar interbody
      fusion: systematic review and economic evaluation.
AB  - PURPOSE: To assess the cost-utility and perioperative costs of minimally invasive
      transforaminal lumbar interbody fusion (MI-TLIF) versus open-TLIF for
      degenerative lumbar pathologies. METHODS: Relevant articles were identified from
      six electronic databases. Predefined end points were extracted and meta-analysis
      conducted from the identified studies. RESULTS: For each study, the direct
      hospital cost for MI-TLIF was found to be less than that of open-TLIF. When these
      outcomes were pooled, direct hospital costs were found to be significantly lower
      in the MI-TLIF group [weighted mean difference (WMD), -$2820; I (2) = 61 %; P <
      0.00001]. MI-TLIF was also associated with shorter hospitalization (WMD, 0.99; 95
      % CI -1.81, -0.17; I (2) = 96 %; P = 0.02), trend toward reduced complications
      (relative risk 0.53; 95 % CI 0.23, 1.06; I (2) = 0 %; P = 0.07), and reduced
      blood loss (WMD, -246.40 mL; I (2) = 98 %; P = 0.003), but was not associated
      with a significant difference in operation time (WMD, -67.05; 95 % CI -169.44,
      35.35; I (2) = 100 %; P = 0.20). CONCLUSIONS: From the limited evidence, the
      available data suggest a trend of significantly reduced perioperative costs,
      length of stay, and blood loss for minimally invasive compared with open surgical
      approaches for TLIF. MI-TLIF may represent an opportunity for optimal utilization
      and allocation of health-care resources from both a hospital and societal
      perspective.

PMID- 26195080
TI  - Giant cystic sacral schwannoma mimicking tarlov cyst: a case report.
AB  - PURPOSE: To present a rare case of a giant schwannoma of the sacrum mimicking a
      Tarlov cyst. METHODS: A 58-year-old woman had a 1-year history of low back pain.
      MRI revealed a large cystic mass in the sacral canal with bony erosion.
      Radiological diagnosis of Tarlov cyst was made. RESULTS: The patient underwent
      surgical treatment for the lesion, which revealed a solid mass. Histopathological
      examination of the tumor confirmed the diagnosis of schwannoma. The postoperative
      course was uneventful and the patient has had significant improvement in her pain
      1 month postoperatively. CONCLUSION: Giant cystic schwannoma of the sacrum is a
      very rare diagnosis overlooked by practitioners for more common cystic
      etiologies, but its treatment is significantly different. Care should be taken to
      include this diagnosis in a differential for a cystic sacral mass.

PMID- 26195081
TI  - Single-stage surgery for compressive thoracic myelopathy associated with
      compressive cervical myelopathy and/or lumbar spinal canal stenosis.
AB  - PURPOSE: The clinical impact of the coexistence of compressive cervical
      myelopathy (CM) and/or lumbar spinal canal stenosis (LCS) with compressive
      thoracic myelopathy (TM) remains unknown. The purpose of this study was to
      examine the incidence, clinical pictures, and surgical outcomes of patients with
      compressive TM and the coexistence of compressive CM and/or LCS. METHODS: We
      retrospectively reviewed 50 patients (18 women and 32 men; mean age 68.4 years)
      who underwent decompression surgery for TM. Mean follow-up period was 44 months.
      The incidence and clinical features of the coexistence of CM and/or LCS were
      investigated. The surgical outcomes after single-stage multilevel decompression
      surgery were also examined using the Japanese Orthopedic Association (JOA)
      scores. RESULTS: Of 50 patients, 35 had concurrent CM and/or LCS (combined
      group), and the remaining 15 only had TM (T group). No significant differences
      were found with regard to sex, the etiology of TM, or the level of thoracic
      stenosis between the groups; however, the patients' age and preoperative JOA
      scores in the combined group were significantly higher than those in the T group.
      In both groups, the JOA score at the final follow-up significantly improved
      compared to the preoperative JOA score. CONCLUSIONS: About 70 % of patients who
      underwent surgery for TM had concurrent CM and/or LCS, and they were initially
      diagnosed with CM or LCS. Single-stage multilevel decompression surgery for TM
      with concurrent CM and/or LCS is comparable to thoracic only surgery with regard
      to complications and surgical results, and it is well tolerated in elderly
      patients.

PMID- 26195082
TI  - Surgical treatment of double thoracic adolescent idiopathic scoliosis with a
      rigid proximal thoracic curve.
AB  - PURPOSE: There is limited consensus on the optimal surgical strategy for double
      thoracic adolescent idiopathic scoliosis (AIS). Recent studies have reported that
      pedicle screw constructs to maximize scoliosis correction cause further thoracic
      spine lordosis. The objective of this study was to apply a new surgical technique
      for double thoracic AIS with rigid proximal thoracic (PT) curves and assess its
      clinical outcomes. METHODS: Twenty one consecutive patients with Lenke 2 AIS and
      a rigid PT curve (Cobb angle >=30o on side-bending radiographs, flexibility <=30
      %) treated with the simultaneous double-rod rotation technique (SDRRT) were
      included. In this technique, a temporary rod is placed at the concave side of the
      PT curve. Then, distraction force is applied to correct the PT curve, which
      reforms a sigmoid double thoracic curve into an approximate single thoracic
      curve. As a result, the PT curve is typically converted from an apex left to an
      apex right curve before applying the correction rod for PT and main thoracic
      curve. RESULTS: All patients were followed for at least 2 years (average 2.7
      years). The average main thoracic and PT Cobb angle correction rate at the final
      follow-up was 74.7 and 58.0 %, respectively. The average preoperative T5-T12
      thoracic kyphosis was 9.3 degrees , which improved significantly to 19.0 degrees 
      (p < 0.0001) at the final follow-up. Although 71 % patients had preoperative
      level shoulders or a positive radiographic shoulder height, all patients had
      mildly imbalanced or balanced shoulders at the final follow-up. The average
      preoperative main thoracic apical vertebral rotation angle of 20.7 degrees 
      improved significantly after surgery to 16.4 degrees  (p = 0.0046), while the
      average preoperative total SRS questionnaire score of 3.7 improved significantly
      to 4.4 (p = 0.0012) at the final follow-up. CONCLUSIONS: Radiographic findings
      and patient outcomes were satisfactory. Thoracic kyphosis can be maintained or
      improved, while coronal and axial deformities can be corrected using SDRRT for
      Lenke 2 AIS with a rigid PT curve.

PMID- 26195083
TI  - In vitro toxicity evaluations of Tibetan medicine Zuota from four institutions.
AB  - Zuota is regarded as the king of Tibetan medicine. However, the major starting
      material of Zuota is mercury, which is one very toxic heavy metal. This has
      aroused serious doubts on the biosafety of Zuota containing drugs. In this study,
      we quantified the Hg contents in four Zuota samples, monitored the release of Hg
      in simulated gastric/intestinal juice and evaluated their cytotoxicity to Caco-2
      cells. Our results showed that the Hg contents in Zuota samples were in the range
      of 566-676 mg/g. Fortunately, the release of Hg from Zuota samples was very low
      in simulated gastric juice, and much lower in simulated intestinal juice. Direct
      contact of Zuota with Caco-2 cells led to dose-dependent cytotoxicity, including
      activity loss and membrane leakage. The toxicity was closely related to
      apoptosis, because the caspase 3/7 levels of Caco-2 cells increased after the
      exposure to Zuota. Interestingly, Zuota samples inhibited the oxidative stress at
      low concentrations, but the toxicity could be relived by antioxidants. The
      possible toxicity should be attributed to the cellular uptake of Zuota
      particulates. Beyond the cytotoxicity, significant differences among Zuota
      samples from different institutions were observed, suggesting that the
      preparation process of Zuota had meaningful influence of its biosafety. The
      implications to the safety and clinical applications of Zuota are discussed. 

PMID- 26195084
TI  - A new NMR approach for structure determination of thermally unstable biflavanones
      and application to phytochemicals from Garcinia buchananii.
AB  - Previous activity-guided phytochemical studies on Garcinia buchananii stem bark,
      which is traditionally used in Africa to treat various gastrointestinal and
      metabolic illnesses, revealed xanthones, polyisoprenylated benzophenones,
      flavanone-C-glycosides, biflavonoids, and/or biflavanones as bioactive key
      molecules. Unequivocal structure elucidation of biflavonoids and biflavanones by
      means of NMR spectroscopy is often complicated by the hindered rotation of the
      monomers around the C-C axis (atropisomerism), resulting in a high spectral
      complexity. In order to facilitate an unrestricted rotation, NMR spectra are
      usually recorded at elevated temperatures, commonly over 80  degrees C, which
      effects in a single set of resonance signals. However, under these conditions,
      one of the target compounds of this investigation, (2R,3S,2"R,3"R)-manniflavanone
      (1), undergoes degradation. Therefore, we demonstrated in the present study that
      the 1,1-ADEQUATE could be successfully used as a powerful alternative approach to
      confirm the C-C connectivities in 1, avoiding detrimental conditions. However, a
      moderate increase in temperature up to 50  degrees C was sufficient to deliver
      sharp signals in the proton NMR experiment of (2R,3S,2"R,3"R)-isomanniflavanone
      (2) and (2"R,3"R)-preussianone (3). In addition, two new compounds could be
      isolated, namely (2R,3S,2"R,3"R)-GB-2 7"-O-beta-D-glucopyranoside (4) and
      (2R,3S,2"R,3"R)-manniflavanone-7"-O-beta-D-glucopyranoside (5), and whose
      structures were elucidated by spectroscopic analysis including 1D and 2D NMR and
      mass spectrometry methods. The absolute configurations were determined by a
      combination of NMR and electronic circular dichroism (ECD) spectroscopy. The
      aforementioned compounds exhibited high anti-oxidative capacity in the H2O2
      scavenging, hydrophilic Trolox equivalent antioxidant capacity (H-TEAC) and
      hydrophilic oxygen radical absorbance capacity (H-ORAC) assays.

PMID- 26195086
TI  - The Code of Professional Conduct for the Neurocritical Care Society.
AB  - Part of the responsibility of a professional society is to establish the
      expectations for appropriate behavior for its members. Some codes are so
      essential to a society that the code itself becomes the central document defining
      the organization and its tenets, as we see with the Hippocratic Oath. In that
      tradition, we have revised the code of professional conduct for the Neurocritical
      Care Society into its current version, which emphasizes guidelines for personal
      behavior, relationships with fellow members, relationships with patients, and our
      interactions with society as a whole. This will be a living document and updated
      as the needs of our society change in time.Available online:
      http://www.neurocriticalcare.org/about-us/bylaws-procedures-and-code-professional
      conduct (1) Code of professional conduct (this document) (2) Leadership code of
      conduct (3) Disciplinary policy. 

PMID- 26195085
TI  - The potential for prevention of dementia across two decades: the prospective,
      population-based Rotterdam Study.
AB  - BACKGROUND: Cardiovascular factors and low education are important risk factors
      of dementia. We provide contemporary estimates of the proportion of dementia
      cases that could be prevented if modifiable risk factors were eliminated, i.e.,
      population attributable risk (PAR). Furthermore, we studied whether the PAR has
      changed across the last two decades. METHODS: We included 7,003 participants of
      the original cohort (starting in 1990) and 2,953 participants of the extended
      cohort (starting in 2000) of the Rotterdam Study. Both cohorts were followed for
      dementia until ten years after baseline. We calculated the PAR of overweight,
      hypertension, diabetes mellitus, cholesterol, smoking, and education.
      Additionally, we assessed the PAR of stroke, coronary heart disease, heart
      failure, and atrial fibrillation. We calculated the PAR for each risk factor
      separately and the combined PAR taking into account the interaction of risk
      factors. RESULTS: During 57,996 person-years, 624 participants of the original
      cohort developed dementia, and during 26,177 person-years, 145 participants of
      the extended cohort developed dementia. The combined PAR in the original cohort
      was 0.23 (95 % CI, 0.05-0.62). The PAR in the extended cohort was slightly higher
      at 0.30 (95 % CI, 0.06-0.76). The combined PAR including cardiovascular diseases
      was 0.25 (95 % CI, 0.07-0.62) in the original cohort and 0.33 (95 % CI, 0.07
      0.77) in the extended cohort. CONCLUSIONS: A substantial part of dementia cases
      could be prevented if modifiable risk factors would be eliminated. Although
      prevention and treatment options of cardiovascular risk factors and diseases have
      improved, the preventive potential for dementia has not declined over the last
      two decades.

PMID- 26195087
TI  - The Effect of Packed Red Blood Cell Transfusion on Cerebral Oxygenation and
      Metabolism After Subarachnoid Hemorrhage.
AB  - BACKGROUND: Anemia adversely affects cerebral oxygenation and metabolism after
      subarachnoid hemorrhage (SAH) and is also associated with poor outcome. There is
      limited evidence to support the use of packed red blood cell (PRBC) transfusion
      to optimize brain homeostasis after SAH. The aim of this study was to investigate
      the effect of transfusion on cerebral oxygenation and metabolism in patients with
      SAH. METHODS: This was a prospective observational study in a neurological
      intensive care unit of a university hospital. Nineteen transfusions were studied
      in 15 consecutive patients with SAH that underwent multimodality monitoring
      (intracranial pressure, brain tissue oxygen, and cerebral microdialysis). Data
      were collected at baseline and for 12 h after transfusion. The relationship
      between hemoglobin (Hb) change and lactate/pyruvate ratio (LPR) orbrain tissue
      oxygen (PbtO2) was tested using univariate and multivariable analyses. RESULTS:
      PRBC transfusion was administered on the median post-bleed day 8. The average Hb
      concentration at baseline was 8.1 g/dL and increased by 2.2 g/dL after
      transfusion. PbtO2 increased between hours 2 and 4 post-transfusion and this
      increase was maintained until hour 10. LPR did not change significantly during
      the 12-h monitoring period. After adjusting for SpO2, cerebral perfusion
      pressure, and LPR, the change in Hb concentration was independently and
      positively associated with a change in PbtO2 (adjusted b estimate = 1.39 [95%
      confidence interval 0.09-2.69]; P = 0.04). No relationship between the change in
      Hb concentration and LPR was found. CONCLUSIONS: PRBC transfusion resulted in
      PbtO2 improvement without a clear effect on cerebral metabolism prior to SAH.

PMID- 26195088
TI  - Bowel Ischemia in Refractory Status Epilepticus: Report of Two Cases and Review
      of the Literature.
AB  - BACKGROUND: Bowel ischemia is a rare life threatening complication seen in
      patients with refractory status epilepticus (RSE). The few reported cases of
      bowel ischemia in this setting have been associated with the use continuous
      barbiturate infusions. We report two patients with RSE in the absence of
      barbiturate infusion and without clear structural, infectious, anatomic,
      vascular, or autoimmune etiology. We review the clinical details of the cases and
      potential factors involved in the development of non-occlusive bowel ischemia in
      patients with RSE. METHODS: The following is a retrospective review of two cases
      of non-occlusive mesenteric ischemia that occurred during the management of RSE.
      The clinical data and the details of pathological examination of the infarcted
      segments of bowel are presented in both cases. RESULTS: In both cases, the bowel
      ischemia occurred in the absence of barbiturate infusion or evidence of clear
      thrombosis, infection, or autoimmune etiology. Case 1 had extensive ischemic
      necrosis of the small bowel with secondary pseudomembrane formation, and case 2
      had full thickness infarction of both the large and small bowel. CONCLUSIONS: The
      mechanism of bowel infarction in these cases is likely multifactorial and was not
      associated with barbiturate use. Likely contributors to ischemia include RSE
      itself, systemic hypotension, vasopressor use, general anesthesia, and abnormal
      cardiac function. During the management of RSE, every effort must be made to
      avoid the secondary complications such as bowel ischemia.

PMID- 26195089
TI  - On the importance of sensor height variation for detection of magnetic labels by
      magnetoresistive sensors.
AB  - Magnetoresistive sensors are widely used for biosensing by detecting the signal
      from magnetic labels bound to a functionalized area that usually covers the
      entire sensor structure. Magnetic labels magnetized by a homogeneous applied
      magnetic field weaken and strengthen the applied field when they are over and
      outside the sensor area, respectively, and the detailed origin of the sensor
      signal in experimental studies has not been clarified. We systematically analyze
      the signal from both a single sensor stripe and an array of sensor stripes as
      function of the geometrical parameters of the sensor stripes as well as the
      distribution of magnetic labels over the stripes. We show that the signal from
      sensor stripes with a uniform protective coating, contrary to conventional wisdom
      in the field, is usually dominated by the contribution from magnetic labels
      between the sensor stripes rather than by the labels on top of the sensor stripes
      because these are at a lower height. We therefore propose a shift of paradigm to
      maximize the signal due to magnetic labels between sensor stripes. Guidelines for
      this optimization are provided and illustrated for an experimental case from the
      literature. 

PMID- 26195090
TI  - Oral supplementation with fish oil reduces dryness and pruritus in the acetone
      induced dry skin rat model.
AB  - BACKGROUND: Pruritus and discomfort are often present in patients with xerosis
      and atopic dermatitis. Several studies suggest an important role of diet in skin
      pathophysiology. OBJECTIVE: This study evaluated the effect of dietary fatty
      acids in the skin physiology via an itch-related animal model with and without
      supplementation with fish oil (FO), a source of polyunsaturated fatty acids
      (PUFA), especially omega 3 (n-3). METHODS: Male Wistar rats were divided into two
      groups-non-supplemented (control) and supplemented with FO (3g/kg/day) by gavage
      for 90 days. Every 30 days, scratching and skin parameters (transepidermal water
      loss (TEWL), hydration, and local blood flow) were evaluated before and after
      dorsal skin exposure to acetone to induce the itch-related dry skin. At the end
      of the study, animals were sacrificed, and skin samples collected for fatty acids
      composition analysis by GC-FID. RESULTS: FO supplementation reduced the TEWL and
      increased the skin hydration, with significant changes from day 60 on, while skin
      microcirculation registered no changes. It also alleviated the acetone induced
      skin barrier alteration, revealed by a faster resolution of TEWL and hydration,
      and elimination of itch-related scratching induced by dry skin. These changes
      were associated with the shift in the skin fatty acids incorporation pattern
      (richer in n-3 with n-6/n-3<5) resulting from the FO supplementation. CONCLUSION:
      Skin barrier dynamics seem to be influenced by FO n-3 PUFA, with suppressive
      effects on the scratching behaviour induced by dry skin. Hence, long-term
      supplementation with n-3 PUFA rich nutrients might reinforce and restore
      cutaneous integrity and function.

PMID- 26195091
TI  - Steroidal contraceptives and bone fractures in women: evidence from observational
      studies.
AB  - BACKGROUND: Age-related decline in bone mass increases the risk of skeletal
      fractures, especially those of the hip, spine, and wrist. Steroidal
      contraceptives have been associated with changes in bone mineral density in
      women. Whether such changes affect the risk of fractures later in life is
      unclear. Hormonal contraceptives are among the most effective and most widely
      used contraceptives. Concern about fractures may limit the use of these effective
      contraceptives. Observational studies can collect data on premenopausal
      contraceptive use as well as fracture incidence later in life. OBJECTIVES: We
      systematically reviewed the evidence from observational studies of hormonal
      contraceptive use for contraception and the risk of fracture in women. SEARCH
      METHODS: Through June 2015, we searched for observational studies. The databases
      included PubMed, POPLINE, Cochrane Central Register of Controlled Trials
      (CENTRAL), LILACS, EMBASE, CINAHL, and Web of Science. We also searched for
      recent clinical trials through ClinicalTrials.gov and the ICTRP. For other
      studies, we examined reference lists of relevant articles and wrote to
      investigators for additional reports. SELECTION CRITERIA: We included cohort and
      case-control studies of hormonal contraceptive use. Interventions included
      comparisons of a hormonal contraceptive with a non-hormonal contraceptive, no
      contraceptive, or another hormonal contraceptive. The primary outcome was the
      risk of fracture. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted the data. One author entered the data into RevMan, and a second author
      verified accuracy. We examined the quality of evidence using the Newcastle-Ottawa
      Quality Assessment Scale (NOS), developed for case-control and cohort studies.
      Sensitivity analysis included studies of moderate or high quality based on our
      assessment with the NOS.Given the need to control for confounding factors in
      observational studies, we used adjusted estimates from the models as reported by
      the authors. Where we did not have adjusted analyses, we calculated the odds
      ratio (OR) with 95% confidence interval (CI). Due to varied study designs, we did
      not conduct meta-analysis. MAIN RESULTS: We included 14 studies (7 case-control
      and 7 cohort studies). These examined oral contraceptives (OCs), depot
      medroxyprogesterone acetate (DMPA), and the hormonal intrauterine device (IUD).
      This section focuses on the sensitivity analysis with six studies that provided
      moderate or high quality evidence.All six studies examined oral contraceptive
      use. We noted few associations with fracture risk. One cohort study reported OC
      ever-users had increased risk for all fractures (RR 1.20, 95% CI 1.08 to 1.34).
      However, a case-control study with later data from a subset reported no
      association except for those with 10 years or more since use (OR 1.55, 95% CI
      1.03 to 2.33). Another case-control study reported increased risk only for those
      who had 10 or more prescriptions (OR 1.09, 95% CI 1.03 to 1.16). A cohort study
      of postmenopausal women found no increased fracture risk for OC use after
      excluding women with prior fracture. Two other studies found little evidence of
      association between OC use and fracture risk. A cohort study noted increased risk
      for subgroups, such as those with longer use or specific intervals since use. A
      case-control study reported increased risk for any fracture only among young
      women with less than average use.Two case-control studies also examined progestin
      only contraceptives. One reported increased fracture risk for DMPA ever-use (OR
      1.44, 95% CI 1.01 to 2.06), more than four years of use (OR 2.16, 95% CI 1.32 to
      3.53), and women over 50 years old. The other reported increased risk for any
      past use, including one or two prescriptions (OR 1.17, 95% CI 1.07 to 1.29) and
      for current use of 3 to 9 prescriptions (OR 1.36, 95% CI 1.15 to 1.60) or 10 or
      more (OR 1.54, 95% CI 1.33 to 1.78). For the levonorgestrel-releasing IUD, one
      study reported reduced fracture risk for ever-use (OR 0.75, 95% CI 0.64 to 0.87)
      and for longer use. AUTHORS' CONCLUSIONS: Observational studies do not indicate
      an overall association between oral contraceptive use and fracture risk. Some
      reported increased risk for specific user subgroups. DMPA users may have an
      increased fracture risk. One study indicated hormonal IUD use may be associated
      with decreased risk. Observational studies need adjusted analysis because the
      comparison groups usually differ. Investigators should be clear about the
      variables examined in multivariate analysis.

PMID- 26195092
TI  - Excessive Body Weight in Older Adults.
AB  - The health challenges prompted by obesity in the older adult population are
      poorly recognized and understudied. A defined treatment of geriatric obesity is
      difficult to establish, as it must take into account biological heterogeneity,
      age-related comorbidities, and functional limitations (sarcopenia/dynapenia).
      This retrospective article highlights the current understanding of the optimal
      body mass index (BMI) in later life, addressing appropriate recommendations based
      on BMI category, age, and health history. The findings of randomized control
      trials of weight loss/maintenance interventions help one to move closer to
      evidence-based and appropriately individualized recommendations for body weight
      management in older adults. 

PMID- 26195093
TI  - Protein and Older Persons.
AB  - An optimal protein intake is important for the preservation of muscle mass,
      functionality, and quality of life in older persons. In recent years, new
      recommendations regarding the optimal intake of protein in this population have
      been published. Based on the available scientific literature, 1.0 to 1.2 g
      protein/kg body weight (BW)/d are recommended in healthy older adults. In certain
      disease states, a daily protein intake of more than 1.2 g/kg BW may be required.
      The distribution of protein intake over the day, the amount per meal, and the
      amino acid profile of proteins are also discussed. 

PMID- 26195094
TI  - Gastric Emptying in the Elderly.
AB  - Aging is characterized by a diminished homeostatic regulation of physiologic
      functions, including slowing of gastric emptying. Gastric and small intestinal
      motor and humoral mechanisms in humans are complex and highly variable: ingested
      food is stored, mixed with digestive enzymes, ground into small particles, and
      delivered as a liquefied form into the duodenum at a rate allowing efficient
      digestion and absorption. In healthy aging, motor function is well preserved
      whereas deficits in sensory function are more apparent. The effects of aging on
      gastric emptying are relevant to the absorption of oral medications and the
      regulation of appetite, postprandial glycemia, and blood pressure. 

PMID- 26195095
TI  - Vitamin Supplementation in the Elderly.
AB  - Vitamin supplementation is fairly common among the elderly. Supplements are often
      used to prevent disease and improve health. In the United States, the use of
      dietary supplements has continued to increase over the last 30 years, and more
      than half of adults report using one or more dietary supplements. Epidemiologic
      evidence suggests that a diet rich in fruits and vegetables does have a
      protective effect on health. However, clinical trials on the use of vitamin
      supplements for promotion of health and prevention of disease have failed to
      demonstrate the strong associations seen in observational studies.

PMID- 26195096
TI  - Sarcopenia as the Biological Substrate of Physical Frailty.
AB  - Physical function decreases with aging, which may result in adverse outcomes (eg,
      disability, loss of independence, institutionalization, death). Physical function
      impairment is a common trait of frailty and sarcopenia. These two conditions,
      albeit highly common, have not yet received a unique operational definition,
      which has impeded their implementation in standard practice. Here, we introduce a
      conceptual model in which sarcopenia is proposed as the biological substrate and
      the pathway whereby the consequences of physical frailty develop. This
      conceptualization may open new venues for the design of interventions against
      physical frailty and promote the translation of findings to the clinical arena. 

PMID- 26195097
TI  - Frailty, Exercise and Nutrition.
AB  - This article first reports the spontaneous course of frailty conditions, and then
      focuses on randomized, controlled frailty interventions (such as physical
      exercise, nutrition, combined exercise plus nutrition, and multifactorial
      interventions) or metaanalysis in community-dwelling older adults or volunteers
      published in 2012, 2013, and 2014. The main take-home messages that emerge from
      recent literature are summarized. 

PMID- 26195098
TI  - Dehydration, Hypernatremia, and Hyponatremia.
AB  - Disturbances of serum sodium are one of the most common findings in older
      persons. They are also a major cause of hospital admissions and delirium and are
      associated with frailty, falls, and hip fractures. Both hypernatremia and
      hyponatremia are potentially preventable. Treatment involves treating the
      underlying cause and restoring sodium and volume status to normal. The arginine
      vasopressin antagonists, vaptans, have increased the therapeutic armamentarium
      available to physicians. 

PMID- 26195099
TI  - The Role of Nutrition and Physical Activity in Cholesterol and Aging.
AB  - Cholesterol is a precursor of several substances with important biologic
      activities; however, it is common to associate this molecule only with bad
      outcomes. This article reviews the cholesterol metabolism, its functions in the
      human body, its pathogenicity, and its elimination. The modifications in
      biochemical paths of cholesterol in aging are highlighted. Finally, the role of
      diet, physical activity, and exercise in cholesterol management is discussed. 

PMID- 26195100
TI  - Anorexia of Aging.
AB  - The anorexia of aging is common, leading to adverse health consequences. As
      populations age, the impacts from anorexia in the older population are set to
      increase. Only greater awareness will allow for prevention or early intervention.
      This article discusses the physiologic anorexia of aging, highlights contributing
      factors, and proposes management strategies, including screening, especially in
      primary care. Many neuroendocrine factors have been implicated in the
      pathophysiology; it is clear that further human research is necessary if there is
      to be a pharmacologic breakthrough. There are currently no approved pharmacologic
      treatment strategies to prevent or treat the anorexia of aging. 

PMID- 26195101
TI  - Screening for Malnutrition in Older People.
AB  - Malnutrition risk increases with age and level of care. Despite significant
      medical advances, malnutrition remains a significant and highly prevalent public
      health problem of developed countries. Earlier identification and appropriate
      nutrition support may help to reverse or halt the malnutrition trajectory and the
      negative outcomes associated with poor nutritional status. A nutrition screening
      process is recommended to help detect people with protein-energy malnutrition
      (PEM) or at malnutrition risk. Evidence supports that oral nutritional
      supplements and dietary counseling can increase dietary intake and improve
      quality of life in elderly with PEM or at malnutrition risk. This article
      examines nutritional screening and assessment tools designated for older adults. 

PMID- 26195102
TI  - Diabetes, Nutrition, and Exercise.
AB  - Aging is associated with body composition changes that lead to glucose
      intolerance and increased risk of diabetes. The incidence of diabetes increases
      with aging, and the prevalence has increased because of the increased life
      expectancy of the population. Lifestyle modifications through nutrition and
      exercise in combination with medications are the main components of diabetes
      management. The potential benefits of nutrition and exercise intervention in
      older people with diabetes are enormous. Nutrition and exercise training are
      feasible even in frail older people living in care homes and should take into
      consideration individual circumstances, cultural factors, and ethnic preferences.

PMID- 26195103
TI  - Nutrition and Cognition in Aging Adults.
AB  - Numerous longitudinal observational studies have suggested that nutrients, such
      as antioxidants, B vitamins, and omega-3 fatty acids, may prevent cognitive
      decline or dementia. There is very little evidence from well-sized randomized
      controlled trials that nutritional interventions can benefit cognition in later
      life. Nutritional interventions may be more effective in individuals with poorer
      nutritional status or as part of multidomain interventions simultaneously
      targeting multiple lifestyle factors. Further evidence, notably from randomized
      controlled trials, is required to prove or refute these hypotheses. 

PMID- 26195104
TI  - Novel Approaches to Nutrition in Older Persons. Preface.

PMID- 26195105
TI  - Associations between residence at birth and mental health disorders: a spatial
      analysis of retrospective cohort data.
AB  - BACKGROUND: Mental health disorders impact approximately one in four US adults.
      While their causes are likely multifactorial, prior research has linked the risk
      of certain mental health disorders to prenatal and early childhood environmental
      exposures, motivating a spatial analysis to determine whether risk varies by
      birth location. METHODS: We investigated the spatial associations between
      residence at birth and odds of depression, bipolar disorder, and post-traumatic
      stress disorder (PTSD) in a retrospective cohort (Cape Cod, Massachusetts, 1969
      1983) using generalized additive models to simultaneously smooth location and
      adjust for confounders. Birth location served as a surrogate for prenatal
      exposure to the combination of social and environmental factors related to the
      development of mental illness. We predicted crude and adjusted odds ratios (aOR)
      for each outcome across the study area. The results were mapped to identify areas
      of increased risk. RESULTS: We observed spatial variation in the crude odds
      ratios of depression that was still present even after accounting for spatial
      confounding due to geographic differences in the distribution of known risk
      factors (aOR range: 0.61-3.07, P = 0.03). Similar geographic patterns were seen
      for the crude odds of PTSD; however, these patterns were no longer present in the
      adjusted analysis (aOR range: 0.49-1.36, P = 0.79), with family history of mental
      illness most notably influencing the geographic patterns. Analyses of the odds of
      bipolar disorder did not show any meaningful spatial variation (aOR range: 0.58
      1.17, P = 0.82). CONCLUSION: Spatial associations exist between residence at
      birth and odds of PTSD and depression, but much of this variation can be
      explained by the geographic distributions of available risk factors. However,
      these risk factors did not account for all the variation observed with
      depression, suggesting that other social and environmental factors within our
      study area need further investigation.

PMID- 26195106
TI  - Cost effectiveness of nonoperative management versus laparoscopic appendectomy
      for acute uncomplicated appendicitis.
AB  - BACKGROUND: Appendectomy remains the gold standard in the treatment of acute,
      uncomplicated appendicitis in the United States. Nonetheless, there is growing
      evidence that nonoperative management is safe and efficacious. METHODS: We
      constructed a decision tree to compare nonoperative management of appendicitis
      with laparoscopic appendectomy in otherwise healthy adults. Model variables were
      abstracted from a literature review, data from the Healthcare Cost and
      Utilization Project data, the Medicare Physician Fee schedule, and the American
      College of Surgeons Surgical Risk Calculator. Uncertainty surrounding parameters
      of the model was assessed via 1-way and probabilistic sensitivity analyses.
      RESULTS: Operative management cost $12,213 per patient. Nonoperative management
      without interval appendectomy (IA) was the dominant strategy, costing $1,865 less
      and producing 0.03 more quality-adjusted life-years (QALYs). Nonoperative
      management with IA cost $4,271 more than operative management, but yielded only
      0.01 additional QALY. One-way sensitivity analysis suggested operative management
      would become the preferred strategy if the recurrence rate was >40.5% or the
      total cost of appendectomy was decreased to <$5,468. Probabilistic sensitivity
      analysis confirmed nonoperative management without IA was the preferred strategy
      in 95.6% of cases. CONCLUSION: Nonoperative management without IA is the least
      costly, most effective treatment for acute, uncomplicated appendicitis and
      warrants further evaluation in a disease thought to be definitively surgical.

PMID- 26195107
TI  - Understanding the determinants of patient satisfaction with surgical care using
      the Consumer Assessment of Healthcare Providers and Systems surgical care survey
      (S-CAHPS).
AB  - BACKGROUND: Patient satisfaction has been emphasized increasingly in all aspects
      of medicine, including the imposition of financial penalties for
      underperformance. Current measures of patient satisfaction, however, do not
      address aspects specific to the care of operative patients. Therefore, our aim
      was to examine the recently validated Consumer Assessment of Healthcare Providers
      and Systems (S-CAHPS) to determine which aspects of perioperative care are
      predictive of satisfaction with the surgeon. METHODS: All patients undergoing a
      general surgery operation at our institution during a 5-month period were sent a
      modified S-CAHPS within 3 days of discharge. Patients were then divided into 2
      groups: those who rated their surgeon as the best possible and those giving a
      lower rating. Univariate and multivariate analyses were used to determine
      predictors of satisfaction with operative care. S-CAHPS results were then
      compared with other satisfaction measures in a subset of patients. RESULTS: The
      response rate was 45.3% (456/1,007). The average age was 59 +/- 16 years,
      duration of stay was 4.1 +/- 6.6 days, and 23% underwent unscheduled operations.
      A total of 72% of patients rated their surgeon as the best surgeon possible. On
      multivariate analysis, preoperative communication and attentiveness on the day of
      operation were the most important determinants of overall surgeon rating. S-CAHPS
      scores correlated with other standard measures of satisfaction (HCAHPS scores).
      CONCLUSION: S-CAHPS is a novel operative satisfaction tool and is feasible to
      administer to patients undergoing general operative procedures. Surgeon
      characteristics most predictive of high patient satisfaction are effective
      preoperative communication and attentiveness on the day of operation.

PMID- 26195108
TI  - Growth Rates of Microbes in the Oceans.
AB  - A microbe's growth rate helps to set its ecological success and its contribution
      to food web dynamics and biogeochemical processes. Growth rates at the community
      level are constrained by biomass and trophic interactions among bacteria,
      phytoplankton, and their grazers. Phytoplankton growth rates are approximately 1
      d(-1), whereas most heterotrophic bacteria grow slowly, close to 0.1 d(-1); only
      a few taxa can grow ten times as fast. Data from 16S rRNA and other approaches
      are used to speculate about the growth rate and the life history strategy of
      SAR11, the most abundant clade of heterotrophic bacteria in the oceans. These
      strategies are also explored using genomic data. Although the methods and data
      are imperfect, the available data can be used to set limits on growth rates and
      thus on the timescale for changes in the composition and structure of microbial
      communities. 

PMID- 26195109
TI  - Assessment of yellowtail kingfish (Seriola lalandi) as a surrogate host for the
      production of southern bluefin tuna (Thunnus maccoyii) seed via spermatogonial
      germ cell transplantation.
AB  - Germ cell transplantation is an innovative technology for the production of
      interspecies surrogates, capable of facilitating easier and more economical
      management of large-bodied broodstock, such as the bluefin tuna. The present
      study explored the suitability of yellowtail kingfish (Seriola lalandi) as a
      surrogate host for transplanted southern bluefin tuna (Thunnus maccoyii)
      spermatogonial cells to produce tuna donor-derived gametes upon sexual maturity.
      Germ cell populations in testes of donor T. maccoyii males were described using
      basic histology and the molecular markers vasa and dead-end genes. The peripheral
      area of the testis was found to contain the highest proportions of dead-end
      expressing transplantable Type A spermatogonia. T. maccoyii Type A spermatogonia
      enriched preparations were transplanted into the coelomic cavity of 6-10-day-old
      post-hatch S. lalandi larvae. Fluorescence microscopy and polymerase chain
      reaction analysis detected the presence of tuna cells in the gonads of the
      transplanted kingfish fingerlings at 18, 28, 39 and 75 days after
      transplantation, indicating that the transplanted cells migrated to the genital
      ridge and had colonised the developing gonad. T. maccoyii germ cell-derived DNA
      or RNA was not detected at later stages, suggesting that the donor cells were not
      maintained in the hosts' gonads.

PMID- 26195110
TI  - Anti-zinc transporter protein 8 autoantibodies significantly improve the
      diagnostic approach to type 1 diabetes: an Italian multicentre study on
      paediatric patients.
AB  - BACKGROUND AND AIM: Anti-ZnT8 antibodies (ZnT8A) were recently proposed as a new
      independent serological marker in Type 1 diabetes (T1D), leading to a significant
      improvement of the positive predictive value of autoantibody measurement in this
      setting. The aim of this retrospective multicentre study was to investigate ZnT8A
      as a complement to the current T1D autoantibody assays in a large cohort of
      paediatric Italian patients. METHODS: ZnT8A were assessed by ELISA in 213 T1DM
      paediatric patients referred to six different centres in North-East Italy. Fifty
      four were analysed at disease onset, 79 within 4 years from diagnosis and 80
      after 5 or more years from diagnosis. Retrospective data about islet cell
      autoantibodies (ICA), anti-insulin (IAA), anti-glutamate decarboxylase (GADA) and
      anti-protein tyrosine phosphatase IA-2 (IA-2A) antibodies were collected and
      compared. RESULTS: Overall, ZnT8A showed positive results in 106/213 (49.8 %) T1D
      patients and were found in 10 (4.7 %) subjects previously classified as
      autoantibody negative based on the existing markers (GADA, IA-2A, IAA and ICA),
      increasing the overall diagnostic sensitivity from 85.9 to 90.6 %. ZnT8A
      disclosed the same sensitivity (61.1 %) at disease onset as GADA (61.1 %) and
      higher than IA-2A (53.7 %), with only GADA showing much persistence in the long
      term follow-up. Focusing on patients at disease onset, all the ICA positive were
      associated with at least one positive autoantibody among GADA, IA-2A and ZnT8A,
      16.7 % of whom presenting only anti-ZnT8-positive antibodies. CONCLUSION: This
      study confirms ZnT8A as an important additional and independent diagnostic marker
      of T1D and supports its introduction in the routine diagnostic process to replace
      less sensitive methods and improve the overall autoantibody sensitivity.

PMID- 26195111
TI  - Evaluation of DNA typing as a positive identification method for soft and hard
      tissues immersed in strong acids.
AB  - Identification of human remains can be hindered by several factors (e.g.,
      traumatic mutilation, carbonization or decomposition). Moreover, in some criminal
      cases, offenders may purposely adopt various expedients to thwart the victim's
      identification, including the dissolution of body tissues by the use of corrosive
      reagents, as repeatedly reported in the past for Mafia-related murders. By means
      of an animal model, namely porcine samples, we evaluated standard DNA typing as a
      method for identifying soft (muscle) and hard (bone and teeth) tissues immersed
      in strong acids (hydrochloric, nitric and sulfuric acid) or in mixtures of acids
      (aqua regia). Samples were tested at different time intervals, ranging between 2
      and 6h (soft tissues) and 2-28 days (hard tissues). It was shown that, in every
      type of acid, complete degradation of the DNA extracted from soft tissues
      preceded tissue dissolution and could be observed within 4h of immersion.
      Conversely, high molecular weight DNA amenable to STR analysis could be isolated
      from hard tissues as long as cortical bone fragments were still present (28 days
      for sulfuric acid, 7 days for nitric acid, 2 days for hydrochloric acid and aqua
      regia), or the integrity of the dental pulp chamber was preserved (7 days, in
      sulfuric acid only). The results indicate that DNA profiling of acid-treated body
      parts (in particular, cortical bone) is still feasible at advanced stages of
      corrosion, even when the morphological methods used in forensic anthropology and
      odontology can no longer be applied for identification purposes.

PMID- 26195112
TI  - [Bronchopulmonary carcinoid tumors: Tunisian experience with 115 surgically
      treated cases].
AB  - INTRODUCTION: Bronchial carcinoid tumors are rare well-differentiated, neuro
      endocrine tumors, with low-grade malignancy. They are distinguished in two
      different groups: typical and atypical carcinoid. The purpose of this study was
      to review clinical, surgical and pathological characteristics in patients with
      primary bronchopulmonary carcinoid tumors. METHODS: This retrospective study
      included 115 bronchial carcinoid tumors surgically treated at a single
      institution during a twenty-one-year period, between 1992 and 2012. RESULTS:
      There were 56 men and 59 women, with a mean age of 43.73 years. Hundred patients
      had typical carcinoids and 15 atypical carcinoids. The majority of patients were
      symptomatic (96.52%). CT revealed a proximal mass in 51% which was obstructive
      leading to ventilator disorders in 80%. Bronchoscopy showed an endo-bronchial
      tumor in 83.48% of the cases. Anatomical resection had been achieved among 99
      patients, and a conservative resection among 16 patients with typical carcinoid
      tumor. Lymph node metastases were present in 12.17% of the cases. Follow-up
      revealed recurrence in one patient and distant metastasis in 4 others. The 5-year
      survival rate was worse for atypical carcinoid with 45% than typical carcinoid
      with 95%. CONCLUSIONS: Carcinoids are rare malignant tumors, and their outcome is
      usually favorable after surgery. However, local recurrence and/or metastases can
      occur with both typical and atypical carcinoid tumors, justifying the need of
      prompt diagnosis and long-term follow-up. The factors influencing the survival
      included the pathological type, distant metastasis and mediastinal lymph node
      involvement.

PMID- 26195113
TI  - [Hydatid cysts of the liver ruptured into the thorax (about five cases)].
AB  - INTRODUCTION: Hydatid cyst of the liver remains a serious public health problem
      in Tunisia. This benign affection can sometimes cause fatal complications such as
      cyst rupture into the thorax. CLINICAL CASES: We report 5 cases of patients who
      experienced intrathoracic rupture of hydatic cyst of liver. There were four rural
      women and an urban man. Patients were between 60 and 75 years of age. We present
      2 cases of cyst rupture into pleura, 3 cases of hydatid bronchial fistula and 3
      cases of biliothoracic fistulas. Surgical treatment was performed by laparotomy
      in 3 cases, thoracic approach in one case and by thoracoabdominal approach in the
      other case. We deplore one case of early death by hemorrhagic shock. CONCLUSION:
      Authors emphasize the complexity of the management of hydatic cyst of liver
      ruptured into the thorax. Surgical treatment remains responsible of high
      perioperative morbidity and mortality. Early diagnostic and improvement of
      reanimation measures are important to improve the prognosis of this serious
      complication.

PMID- 26195114
TI  - [Arrhythmia and sleep apnea syndrome].
AB  - CONTEXT: Arrhythmia is a major cause of morbidity and mortality in Europe and in
      the United States. The aim of this review article was to assess the results of
      the prospective studies that evaluated the risk of arrhythmia in patients with
      sleep apnea syndrome and discuss the management of this arrhythmia. EVIDENCE
      ACQUISITION: Reports published with the following search terms were searched:
      sleep apnea syndrome, atrial flutter, supraventricular arrhythmia, ventricular
      arrhythmia, ventricular tachycardia, ventricular fibrillation, torsade de pointe,
      atrial fibrillation and sudden death. The investigation was restricted to reports
      published in English and French. EVIDENCE SYNTHESIS: The outcome of this analysis
      suggests that patients with untreated overt sleep apnea syndrome are at increased
      risk of arrhythmia. CONCLUSIONS: The timely recognition and effective treatment
      of sleep apnea syndrome in patients with arrhythmia are mandatory because the
      prognosis of arrhythmia may be improved with the appropriate treatment of sleep
      apnea syndrome.

PMID- 26195115
TI  - [Urinothorax, an unusual cause of pleural effusion].

PMID- 26195116
TI  - [Influence of care pathways on the time of initiation of TB treatment].
AB  - INTRODUCTION: Untreated positive pulmonary TB smear has both individual
      implications, increasing morbidity and mortality, and collective implications,
      increasing the contagiousness of the disease. The present study aims to identify
      the course of patient care and the influence of care pathway on the time of
      initiation of TB treatment in Abidjan. METHODS: We conducted a prospective and
      comparative study between two groups with pulmonary smear-positive: 38 with a
      conventional course (use of only the health facilities) and 198 with mixed
      driving (combining health facilities, self-medication and traditional medicine).
      RESULTS: The average time between onset of symptoms and initiation of treatment
      for patients with conventional path was significantly different from that
      observed in patients with mixed course (4.28 weeks versus 8.57 weeks, P < 0.001).
      Multivariate analysis mixed route was related to level of education (OR=2.728
      [1.165-6.386]; P=0.02), the district of residence (OR=2.690 [1.168-6.195];
      P=0.02), the mode of onset of symptoms (OR=0.33 [0.101-0.6607]; P=0.013) and
      weight loss (OR=0.259 [0.139-0.798]; P=0.004). CONCLUSIONS: The course of
      patients are multiple and can induce delays in starting treatment for
      tuberculosis. The sensitization of the population and the involvement of
      traditional healers in TB screening may contribute to the early therapeutic
      management.

PMID- 26195117
TI  - [Children exposed to multidrug-resistant tuberculosis: How should we manage?
      Analysis of 46 child contacts and review of the literature].
AB  - INTRODUCTION: Tuberculosis-related morbidity and mortality remain important.
      Emergence and diffusion of multidrug-resistance tuberculosis (MDR-TB) is a global
      public health concern. Cases of MDR-TB in children are a sentinel event
      indicating the spread of a mycobacterial strain within a community. Latent TB
      precedes MDR-TB and screening and follow-up of contact individuals are key points
      of TB infection control. METHODS: We performed the case-investigation of 20 adult
      cases of MDR-TB managed in our institution. RESULTS: Forty-six pediatric contact
      individuals were identified. A high proportion of these children were lost to
      follow-up (80% at 12 months), showing that monitoring this reservoir population
      with migrant history is challenging. Five (11%) children presented a secondary
      infection: one child was diagnosed with active TB infection (positive tuberculin
      skin test associated with abnormalities on chest computer tomography [CT] scan).
      Four children were diagnosed with latent TB infection (isolated positive
      tuberculin skin test with normal CT scan). Two of these children received a
      treatment adjusted to the strain of the index case. DISCUSSION: In the setting of
      emerging MDR-TB, tuberculin skin test may be likely replaced by specific
      interferon-gamma release assays (IGRA), independent of prior BCG vaccination. In
      addition, chest CT scan is preferred to chest X-ray to detect TB lesions. The
      management of latent TB infection is controversial: immediate treatment with
      second-line anti-TB drugs adapted to the index case strain or, consistently with
      WHO guidelines, a simple follow-up with subsequent treatment in case of active
      TB.

PMID- 26195118
TI  - [Lung function in patients with diabetes mellitus].
AB  - INTRODUCTION: Diabetes mellitus is a disease affecting a lot of organs. One of
      the little known diabetes complication is impairment of pulmonary function. The
      aim of this study was to compare pulmonary function in two groups: diabetic
      individuals and obese non-diabetic individuals and to investigate predictive
      factors of alteration of diffusing capacity of lung for carbon monoxide (DLCO).
      PATIENTS AND METHOD: We retrospectively included all patients hospitalized in
      department of endocrinology between 1st July 2013 and 31 December 2013 and who
      underwent pulmonary function tests. All these medical charts of patients were
      reviewed and patients were classified in two groups: diabetic and obese non
      diabetic individuals. RESULTS: Overall, 89 patients were included, 62 diabetic
      patients and 27 obese non-diabetic patients. Forced vital capacity (FVC), forced
      expiratory volume in 1 second (FEV1), medium expiratory flow, expiratory residual
      volume, total lung capacity (TLC) and DLCO were significantly lower in patients
      with diabetes mellitus compared to obese non-diabetic patients. A low DLCO was
      significantly associated with diabetic neuropathy, macrovascular complication
      (carotid atheroma), impairment of renal function, and insulin treatment.
      CONCLUSION: Respiratory function is impaired in diabetes mellitus, with a
      significant decrease in FVC, FEV1, TLC and DLCO.

PMID- 26195119
TI  - Agent Orange Exposure and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) in Human
      Milk.
AB  - Agent Orange was sprayed in parts of southern Vietnam during the U.S.-Vietnam war
      and was a mixture of two chlorophenoxy herbicides. The mixture was contaminated
      with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD and other dioxins and
      furans are measurable in the milk of Vietnamese women. We explored whether the
      TCDD in milk from these women was from Agent Orange and whether lactational
      exposure can be a mode of transgenerational effects of TCDD from Agent Orange. A
      review of the world's literature on milk concentrations of polychlorinated
      compounds showed the presence of TCDD and other dioxins and furans in all
      countries that have been assessed. The congener profile of these chemicals, that
      is, the proportion of different congeners in the sample, can be used to assess
      the source of milk contamination. Measurements in most countries, including
      contemporary measurements in Vietnam, are consistent with non-Agent Orange
      exposure sources, including industrial activities and incineration of waste.
      Models and supporting human data suggest that TCDD from breastfeeding does not
      persist in a child past adolescence and that the adult body burden of TCDD is
      independent of whether the individual was breast- or bottle-fed as a child. These
      findings suggest that exposure to Agent Orange in Vietnam did not result in
      persistent transgenerational exposure through human milk. 

PMID- 26195120
TI  - The prognostic impact of age in different molecular subtypes of breast cancer.
AB  - Breast cancer is a heterogeneous entity composed of distinct molecular subgroups
      with different molecular and clinical features. We analyzed the association
      between molecular breast cancer subgroups, age at diagnosis, and prognosis in a
      compilation of publicly available gene expression datasets. Affymetrix gene
      expression data (U133A or U133Plus2.0 arrays) of 4467 breast cancers from 40
      datasets were compiled and homogenized. Breast cancer subgroups were defined
      based on expression of ESR1, PR, HER2, and Ki67. Event-free survival was
      calculated as recurrence-free survival or distant metastasis-free survival if
      recurrence-free survival was not available. Young age at diagnosis is associated
      with higher frequency of triple negative and HER2 subtypes and lower frequency of
      luminal A breast cancers. The 5-year event-free survival rates of patients aged
      less than 40, between 40 and 50, and >50 years were 54.3 +/- 3.5, 68.5 +/- 1.9,
      and 70.4 +/- 1.3 %, respectively. When controlling for breast cancer subtype, we
      found that age <40 years remained significantly associated with poor prognosis in
      triple negative breast cancer. The effect was modest in luminal tumors and not
      found in HER2 subtype. Both subtypes and age retained their significances in
      multivariate analysis. Association of age at diagnosis with molecular breast
      cancer subtype contributes to its important role as prognostic factor among
      patients with breast cancer. Still, within the group of triple negative breast
      cancer, young age <40 years has a significant prognostic value which was retained
      in multivariate analysis.

PMID- 26195121
TI  - Breast cancer risk for Korean women with germline mutations in BRCA1 and BRCA2.
AB  - The average age-specific cumulative risk (penetrance) of breast cancer has been
      studied for BRCA1 and BRCA2 mutation carriers living in Western countries, but
      not for those living in East Asian countries where the population breast cancer
      incidence is lower. From 2007 to 2011, the Korean Hereditary Breast Cancer study
      identified 151 BRCA1 and 225 BRCA2 mutation-carrying families from family cancer
      clinics. We estimated the hazard ratio (HR) for female carriers relative to the
      population, and hence the penetrance, using a modified segregation analysis of
      cancer family histories conditioned on ascertainment. The breast cancer HR
      estimates [95 % confidence interval (CI)] for BRCA1 and BRCA2 mutation carriers
      were 18 (3-103) and 11 (5-27), respectively. The breast cancer penetrance
      estimates (95 % CI) to age 70 years were 49 % (11-98) and 35 % (16-65) for BRCA1
      and BRCA2 mutation carriers, respectively. The breast cancer HR and penetrance
      estimates were similar for Korean and Western women (all P > 0.4). The point
      estimates of breast cancer penetrance were similar to age 50 years, though less
      for Korean carriers at older ages. Breast cancer risk for Korean and Western
      mutation carriers might reflect underlying population risks which in turn likely
      reflect differences in environmental and lifestyle factors. This raises the
      possibility of identifying modifiers of cancer risk for carriers with
      implications for prevention.

PMID- 26195122
TI  - In vitro and in vivo studies of the combination of IGF1R inhibitor figitumumab
      (CP-751,871) with HER2 inhibitors trastuzumab and neratinib.
AB  - The insulin-like growth factor I receptor (IGF1R) has been linked to resistance
      to HER2-directed therapy with trastuzumab (Herceptin). We examined the anti-tumor
      activity of figitumumab (CP-751,871), a human monoclonal antibody that blocks
      IGF1R ligand binding, alone and in combination with the therapeutic anti-HER2
      antibody trastuzumab and the pan-HER family tyrosine kinase inhibitor neratinib,
      using in vitro and in vivo breast cancer model systems. In vitro assays of
      proliferation, apoptosis, and signaling, and in vivo anti-tumor experiments were
      conducted in HER2-overexpressing (BT474) and HER2-normal (MCF7) models. We find
      single-agent activity of the HER2-targeting drugs but not figitumumab in the
      BT474 model, while the reverse is true in the MCF7 model. However, in both
      models, combining figitumumab with HER2-targeting drugs shows synergistic anti
      proliferative and apoptosis-inducing effects, and optimum inhibition of
      downstream signaling. In murine xenograft models, synergistic anti-tumor effects
      were observed in the HER2-normal MCF7 model for the combination of figitumumab
      with trastuzumab, and, in the HER2-overexpressing BT474 model, enhanced anti
      tumor effects were observed for the combination of figitumumab with either
      trastuzumab or neratinib. Analysis of tumor extracts from the in vivo experiments
      showed evidence of the most optimal inhibition of downstream signaling for the
      drug combinations over the single-agent therapies. These results suggest promise
      for such combinations in treating patients with breast cancer, and that, unlike
      the case for single-agent therapy, the therapeutic effects of such combinations
      may be independent of expression levels of the individual receptors or the single
      agent activity profile. 

PMID- 26195124
TI  - Perceived facilitators to change in hospital pharmacy practice in England.
AB  - BACKGROUND: Traditionally, hospital pharmacists' roles have been associated with
      dispensing medications prescribed by doctors and offering advice about medicines
      to patients and other healthcare professionals. In England, significant changes
      in the structure of hospital pharmacy practice began in the 1970s and currently
      hospital pharmacists are undertaking a number of advanced roles including
      prescribing. OBJECTIVE: This study investigated the facilitators to change in
      hospital pharmacy practice in England in order to identify lessons that might
      assist in the potential changes needed in other countries for extended clinical
      roles. SETTING: The study was conducted in England. METHODS: A qualitative study
      using semi-structured interviews was conducted with 28 participants, comprising
      22 pharmacists and 6 pharmacy technicians from England. They were recruited
      through a snowball sampling technique. Transcribed interviews were entered into
      the QSR NVivo 10 software for data management and analysed thematically. Main
      outcome measure Pharmacists and pharmacy technicians' perception of the
      facilitators to hospital pharmacy practice change in England. RESULT: Three major
      themes emerged from this study: drivers for change, strategies for change and
      efficiency. Many of the drivers identified were linked to changes in the
      structure of hospital pharmacy including education and training; specialisation
      in practice and career structure. Strategies employed to achieve practice change
      included broadening the role of pharmacy technicians in order to free-up
      pharmacists' time; seizing opportunities for extended roles; developing a
      relationship with the medical profession and professional leadership influence.
      Participants perceived that the development of pharmacists' clinical roles have
      resulted in a more efficient healthcare provision where patients were offered
      seamless services. CONCLUSION: Changes in the professional structure of pharmacy
      including education and training, specialisation, career structure and the roles
      of pharmacy technicians could benefit the development of pharmacists' clinical
      roles in other countries.

PMID- 26195123
TI  - Rectal indomethacin versus placebo to reduce the incidence of pancreatitis after
      endoscopic retrograde cholangiopancreatography: results of a controlled clinical
      trial.
AB  - BACKGROUND: Acute pancreatitis is the most common major complication after
      endoscopic retrograde cholangiopancreatography (ERCP). Many drugs have been
      evaluated for prophylaxis, including nonsteroidal anti-inflammatory drugs
      (NSAIDs), which are potent inhibitors of phospholipase A2 and play a role in the
      pathogenesis of acute pancreatitis. Rectal NSAIDs have been shown in prospective
      studies to decrease the incidence of this complication, but the indication is not
      generalized in clinical practice. The aim of this study was to evaluate the
      efficacy of rectal administration of indomethacin in reducing the incidence of
      post-ERCP pancreatitis in high-risk patients. METHODS: This was a controlled
      clinical trial where patients with an elevated risk of developing post-ERCP
      pancreatitis were assigned to receive 100 mg of rectal indomethacin or a 2.6 g
      suppository of glycerin immediately after ERCP, without placement of a pancreatic
      stent. The patients were determined to be at high risk based on validated patient
      and procedure-related risk factors. Post-ERCP pancreatitis was defined as the
      presence of new upper abdominal pain, hyperamylasemia/hyperlipasemia (at least
      three times the upper limit) 2 hours after the procedure and hospitalization at
      least 48 hours because of the complication. Pancreatitis severity was defined
      according to Cotton's criteria. RESULTS: One hundred sixty-six patients were
      included; 82 in the study group and 84 in the placebo group. Patients had at
      least one major and/or two minor risk factors for developing post-ERCP
      pancreatitis. The incidence of the complication was 4.87% (4/82) in the study
      group and 20.23% (17/84) in the placebo group; this difference was significant (P
      = 0.01). According to Cotton's criteria, 17 patients (80.9%) developed mild
      pancreatitis and 4 (19.1%) had moderate pancreatitis; 3 of these 4 patients
      belonged to the placebo group (P = 0.60). Based on these results, an absolute
      risk reduction of 0.15 (15%), a relative risk reduction of 0.75 (75%) and a
      number needed to treat of 6.5 patients were calculated to prevent an episode of
      post-ERCP pancreatitis. There was no mortality. CONCLUSIONS: Rectal indomethacin
      reduced the incidence of post-ERCP pancreatitis among patients at high risk of
      developing this complication. TRIAL REGISTRATION: National Clinical Trials
      NCT02110810. Date April 7, 2014.

PMID- 26195125
TI  - Pregnancy outcome after exposure to the novel oral anticoagulant rivaroxaban in
      women at suspected risk for thromboembolic events: a case series from the German
      Embryotox Pharmacovigilance Centre.
AB  - BACKGROUND: New oral anticoagulants are increasingly used in women of
      childbearing age, but apart from one case report there is no published experience
      with rivaroxaban exposure during pregnancy. METHODS: From October 2008 to
      December 2014, the German Embryotox Pharmacovigilance Centre identified 63
      exposed pregnancies among 94 requests concerning rivaroxaban use during
      childbearing age. Follow-up included paediatric checks until 6 weeks after birth.
      RESULTS: All pregnancies with completed follow-up were exposed at least during
      the first trimester. Treatment indications included venous thromboembolism, knee
      surgery, and atrial fibrillation. 37 pregnancies were prospectively ascertained
      and resulted in six spontaneous abortions, eight elective terminations of
      pregnancy, and 23 live births. All women had discontinued rivaroxaban after
      recognition of pregnancy, mostly in the first trimester, but in one woman
      treatment continued until gestational week 26. There was one major malformation
      (conotruncal cardiac defect) among the 37 prospectively ascertained pregnancies
      in a woman with complex medication and a previous foetus with cardiac
      malformation without exposure to rivaroxaban. Only one case of bleeding
      concerning a retrospective report of surgery for missed abortion was observed in
      our case series. CONCLUSION: Our results might give reassurance to those women,
      who were inadvertently exposed to rivaroxaban in early pregnancy. However, our
      limited cohort size does not allow ruling out an increased malformation risk and
      does not support the use of rivaroxaban during pregnancy. In all cases of
      (inadvertent) rivaroxaban exposure during 1st trimester, anticoagulation regimen
      should be reconsidered and a detailed ultrasound assessment recommended to
      confirm normal foetal development.

PMID- 26195127
TI  - Obtaining equilibrium states in ultrasoft cluster forming systems using a
      combined thermo- and barostat.
AB  - By compressing a (two-dimensional) system of ultrasoft, cluster-forming particles
      via a combined thermo- and barostat, a cluster crystal is created that is
      obviously not in its equilibrium: launching from such a configuration expansion
      and compression runs leads to systems that differ in their density distinctively
      from the one of the initial state. With our analysis we can discard dynamic lag
      as the origin of these discrepancies and can confirm that they occur due to the
      complex interplay between the two mechanisms which accompany any change in volume
      of a cluster crystal, namely the variation of the lattice spacing and of the
      number of lattice sites. In our investigations we show that only combined melting
      and annealing runs are able to transform the system in its equilibrium. This is
      evidenced by the fact that the density of this state remains unchanged even after
      the application of combined compression- and expansion-experiments as well as
      combined melting- and annealing-runs; furthermore, the cluster crystal shows an
      essentially perfect hexagonal arrangement. 

PMID- 26195126
TI  - Estimation of inbreeding using pedigree, 50k SNP chip genotypes and full sequence
      data in three cattle breeds.
AB  - BACKGROUND: Levels of inbreeding in cattle populations have increased in the past
      due to the use of a limited number of bulls for artificial insemination. High
      levels of inbreeding lead to reduced genetic diversity and inbreeding depression.
      Various estimators based on different sources, e.g., pedigree or genomic data,
      have been used to estimate inbreeding coefficients in cattle populations.
      However, the comparative advantage of using full sequence data to assess
      inbreeding is unknown. We used pedigree and genomic data at different densities
      from 50k to full sequence variants to compare how different methods performed for
      the estimation of inbreeding levels in three different cattle breeds. RESULTS:
      Five different estimates for inbreeding were calculated and compared in this
      study: pedigree based inbreeding coefficient (F(PED)); run of homozygosity (ROH)
      based inbreeding coefficients (F(ROH)); genomic relationship matrix (GRM)-based
      inbreeding coefficients (F(GRM)); inbreeding coefficients based on excess of
      homozygosity (F(HOM)) and correlation of uniting gametes (F(UNI)). Estimates
      using ROH provided the direct estimated levels of autozygosity in the current
      populations and are free effects of allele frequencies and incomplete pedigrees
      which may increase in inaccuracy in estimation of inbreeding. The highest
      correlations were observed between F(ROH) estimated from the full sequence
      variants and the F(ROH) estimated from 50k SNP (single nucleotide polymorphism)
      genotypes. The estimator based on the correlation between uniting gametes
      (F(UNI)) using full genome sequences was also strongly correlated with F(ROH)
      detected from sequence data. CONCLUSIONS: Estimates based on ROH directly
      reflected levels of homozygosity and were not influenced by allele frequencies,
      unlike the three other estimates evaluated (F(GRM), F(HOM) and FU(NI)), which
      depended on estimated allele frequencies. F(PED) suffered from limited pedigree
      depth. Marker density affects ROH estimation. Detecting ROH based on 50k chip
      data was observed to give estimates similar to ROH from sequence data. In the
      absence of full sequence data ROH based on 50k can be used to access homozygosity
      levels in individuals. However, genotypes denser than 50k are required to
      accurately detect short ROH that are most likely identical by descent (IBD).

PMID- 26195128
TI  - A Novel Four-step Approach for Systematic Identification of Naphthoquinones in
      Juglans cathayensis Dode using Various Scan Functions of Liquid Chromatography
      Tandem Mass Spectrometry along with Data Mining Strategies.
AB  - INTRODUCTION: Systematic analyses of naphthoquinones in Juglans cathayensis have
      not yet been reported. It is very challenging to identify naphthoquinones with
      various structural diversities, especially those at trace levels. OBJECTIVE: To
      develop an efficient analytical approach for systematic discovery and
      identification of naphthoquinones in Juglans cathayensis. METHODOLOGY: A novel
      four-step approach was evaluated by utilizing various scan functions of liquid
      chromatography-triple quadrupole-linear ion trap mass spectrometry (LC-QTRAP
      MS/MS) and liquid chromatography-quadrupole time-of-flight tandem mass
      spectrometry (LC-QTOF-MS/MS) along with data mining strategies. First, MS/MS
      fragmentation behaviors of naphthoquinones were investigated. Second, multiple
      ion monitoring triggered enhanced product ion scan (MIM-EPI) with specified ions
      was conducted to identify targeted naphthoquinones. Third, other scan functions
      of QTRAP-MS/MS and data mining strategies were explored to identify untargeted
      naphthoquinones. Fourth, structural rationalization and confirmation of
      naphthoquinones were performed using QTOF-MS/MS via its accurate mass measurement
      and MS/MS fragmentation functions. RESULTS: Optimal scan methods and data mining
      strategies using QTRAP-MS/MS were obtained for identification of targeted and
      untargeted naphthoquinones. Consequently, 48 naphthoquinones including 24 novel
      ones were identified or tentatively identified from Juglans cathayensis.
      CONCLUSION: A novel four-step approach for efficient discovery and identification
      of naphthoquinones was developed by exploring various scan functions of current
      LC-MS/MS technologies and data mining strategies, providing an example for
      systematic characterization of certain classes of phytochemicals, especially
      trace analytes in complex samples.

PMID- 26195129
TI  - The Soft Triangle: An Often Neglected Area in Rhinoplasty.
AB  - BACKGROUND: This study aims to focus on one of the lesser mentioned topics in
      discussions of aesthetic nose operations, the soft triangle. In addition to
      outlining the characteristics of the area, the various complications specific to
      the soft triangle are discussed along with methods and techniques utilized by the
      authors to avoid such complications. METHODS: One hundred twenty-seven of 841 (15
      %) patients who were assessed both preoperatively and intraoperatively for the
      presence of an anatomical issue of the soft triangle were included in the study.
      Patients were divided into three groups according to their anatomical features
      that were identified intraoperatively. The preoperative and postoperative
      photographs of all patients were compared to assess the effects of the respective
      soft triangle grafts on both nostril length and the nostril/lobule harmony.
      RESULTS: The average follow-up time of the patients was 27 months (6-60).
      Postoperative notching (of various degrees) was found in six (6/127) total
      patients: one (1/31) patient in the first group, two (2/24) patients in the
      second group, and three (3/72) patients in the third group. CONCLUSION:
      Neglecting the soft triangle area might yield grim results in terms of cosmetic
      and functional aspects. To avoid these problems, incisions should be planned
      purposefully, and patients who have anatomically weak support should be
      identified so that additional precautions should be taken for these cases. 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- 26195130
TI  - Proximally Based Anterolateral-Thigh (ALT) Flap for Knee Reconstruction: An
      Advancement Propeller Perforator Flap.
AB  - BACKGROUND: Adequate coverage of the knee region is often challenging for plastic
      and orthopedic surgeons. In the last decade, among several reconstructive
      techniques, local perforator flaps have become useful reconstructive units. After
      a wide resection for soft-tissue sarcoma, the knee vascular web may be reasonably
      damaged and, consequently, perforator flaps based on a local pedicle [such as the
      distally based anterolateral thigh (ALT) flap] are not reliable. Thus, we
      harvested a proximally based ALT for knee coverage. METHODS: A 52-year-old man
      underwent local radiation therapy and a wide resection of a soft-tissue sarcoma
      on the anterior-lateral aspect of the left knee, which resulted in a 15 * 10 cm
      defect. The defect was covered with a proximally based ALT, through an
      advancement and propeller relocation of its skin paddle. RESULTS: All margins
      were tumor free. After 5 days, the donor site was closed primarily because of
      edema. Neither necrosis of the flap nor dehiscence of the wound was detected. No
      local relapses were detected at 6-month follow-up. CONCLUSIONS: In case of soft
      tissue defects of the knee region, with likely involvement of the local vascular
      web, a local perforator solution is the advancement and propeller proximally
      based ALT flap. 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- 26195131
TI  - Non-motor symptoms and quality of life in tremor dominant vs postural instability
      gait disorder Parkinson's disease patients.
AB  - OBJECTIVES: To explore the differences in the features and impact on quality of
      life (QOL) of non-motor symptoms (NMS) of tremor dominant (TD) and postural
      instability gait disorder (PIGD) phenotypes early Parkinson's disease (PD), as
      well as the determinants of poor QOL for TD and PIGD phenotypes. METHODS: This
      cross-sectional study recruited 301 patients with early PD and 101 healthy
      controls. Specific assessments used for NMS included NMS scale (NMSS), the
      Hamilton Rating Scale for Depression (HRSD-24), the Hamilton Anxiety Scale
      (HAMA), the Mini-Mental state examination (MMSE), and Addenbrooke's Cognitive
      Exam-Revised (ACE-R). QOL was evaluated with the PD Quality of Life Questionnaire
      (PDQ-39). RESULTS: Tremor dominant phenotype patients were 117 (38.9%), and PIGD
      were 155 (51.5%). Compared with TD patients, patients with PIGD had higher
      frequency of NMS (9.0 +/- 5.3 vs 6.7 +/- 4.6, P < 0.001), NMSS total scores (39.6
      +/- 34.5 vs 24.4 +/- 22.7, P < 0.001) and more poorly for PDQ-39 summary index
      (19.2 +/- 14.0 vs 13.8 +/- 11.5, P = 0.001). There was no difference in the
      impact of NMS measured with NMSS on QOL between PIGD and TD phenotypes. PIGD
      phenotype had little impact on poor QOL once the effect of depression was taken
      into account. Depression was a primary negative predictor for QOL in both TD and
      PIGD patients (Beta: 0.697 and 0.619, respectively, P < 0.001). CONCLUSIONS: PIGD
      phenotype had a higher prevalence of NMS and worse QOL than TD phenotype.
      Depression is related to a dramatic decline in QOL in both TD and PIGD phenotype
      patients with PD.

PMID- 26195132
TI  - Modulation of Energy Conversion Processes in Carbonaceous Molecular Bearings.
AB  - The energetics and photodynamics of carbonaceous molecular bearings with discrete
      molecular structures were investigated. A series of supramolecular bearings
      comprising belt-persistent tubular cycloarylene and fullerene molecules accepted
      photonic stimuli to afford charge-separated species via a photoinduced electron
      transfer process. The energy conversion processes associated with the
      photoexcitation, however, differed depending on the molecular structure. A pi
      lengthened tubular molecule allowed for the emergence of an intermediary triplet
      excited state at the bearing, which should lead to an energy conversion to
      thermal energy. On the other hand, low-lying charge-separated species induced by
      an endohedral lithium ion in fullerene enabled back electron transfer processes
      to occur without involving triplet excited species. The structure-photodynamics
      relationship was analyzed in terms of the Marcus theory to reveal a large
      electronic coupling in this dynamic supramolecular system. 

PMID- 26195133
TI  - A new sagittal parameter to estimate pelvic tilt using the iliac cortical density
      line and iliac tilt: a retrospective X-ray measurement study.
AB  - BACKGROUND: When spinal kyphosis increases, the compensatory mechanism activates
      and the pelvic position changes. Increasing the pelvic tilt, which is the
      orientation of the pelvis with respect to the femoral head, is known to associate
      with the clinical symptoms in kyphosis in the aging population. It is often
      difficult to detect the femoral head on radiographs, limiting the ability to
      determine the pelvic tilt. Therefore, there is a need to establish another
      parameter independent of the femoral head which closely correlates with the
      pelvic tilt. METHODS: Eighty-two adult patients with full-length lateral standing
      spine radiographs were recruited (mean age: 73.0 years). A new parameter, the
      iliac cortical density line (a component of the arcuate line of the ilium) and
      the iliac tilt (defined as the angle between the iliac cortical density line and
      the vertical), was analyzed to determine the correlation with the pelvic tilt.
      RESULTS: Both the pelvic tilt (PT) and iliac tilt (IT) could be identified in 67
      patients, and a significant correlation was observed between the PT and IT (r =
      0.86, P < 0.0001). The PT could be estimated using the following formula: PT = IT
      - 12.9 (in females), PT = IT - 16.7 (in males). CONCLUSIONS: The iliac tilt,
      which can be easily and directly measured using the iliac cortical density line,
      is a new parameter that can reliably estimate the pelvic tilt even when the
      femoral head is not detectable on the radiograph.

PMID- 26195135
TI  - A new approach to blood flow simulation in vascular networks.
AB  - A proper analysis of blood flow is contingent upon accurate modelling of the
      branching pattern and vascular geometry of the network of interest. It is
      challenging to reconstruct the entire vascular network of any organ
      experimentally, in particular the pulmonary vasculature, because of its very high
      number of vessels, complexity of the branching pattern and poor accessibility in
      vivo. The objective of our research is to develop an innovative approach for the
      reconstruction of the full pulmonary vascular tree from available morphometric
      data. Our method consists of the use of morphometric data on those parts of the
      pulmonary vascular tree that are too small to reconstruct by medical imaging
      methods. This method is a three-step technique that reconstructs the entire
      pulmonary arterial tree down to the capillary bed. Vessels greater than 2 mm are
      reconstructed from direct volume and surface analysis using contrast-enhanced
      computed tomography. Vessels smaller than 2 mm are reconstructed from available
      morphometric and distensibility data and rearranged by applying Murray's laws.
      Implementation of morphometric data to reconstruct the branching pattern and
      applying Murray's laws to every vessel bifurcation simultaneously leads to an
      accurate vascular tree reconstruction. The reconstruction algorithm generates
      full arterial tree topography down to the first capillary bifurcation. Geometry
      of each order of the vascular tree is generated separately to minimize the
      construction and simulation time. The node-to-node connectivity along with the
      diameter and length of every vessel segment is established and order numbers,
      according to the diameter-defined Strahler system, are assigned. In conclusion,
      the present model provides a morphological foundation for future analysis of
      blood flow in the pulmonary circulation.

PMID- 26195136
TI  - Hybrid pyrimidine alkynyls inhibit the clinically resistance related Bcr
      Abl(T315I) mutant.
AB  - A series of pyrimidine alkynyl derivatives were designed and synthesized as new
      Bcr-Abl inhibitors by hybriding the structural moieties from GNF-7, ponatinib and
      nilotinib. One of the most potent compounds 4e strongly suppresses Bcr-Abl(WT)
      and Bcr-Abl(T315I) kinase with IC50 values of 5.0 and 9.0 nM, and inhibits the
      proliferation of K562 and murine Ba/F3 cells ectopically expressing Bcr
      Abl(T315I) cells with IC50 values of 2 and 50 nM, respectively. It also displays
      good pharmacokinetics properties with an oral bioavailability of 35.3% and T(1/2)
      value of 48.7 h, and demonstrates significantly suppression on tumor growth in
      xenografted mice of K562 and Ba/F3 cells expressing Bcr-Abl(T315I). These
      inhibitors may serve as lead compounds for further developing new anticancer
      drugs overcoming the clinically acquired resistance against current Bcr-Abl
      inhibitors.

PMID- 26195134
TI  - Evolutionary history of the Azteca-like mariner transposons and their host ants.
AB  - Three different complete mariner elements were found in the genome of the ant
      Tapinoma nigerrimum. One (Tnigmar-Mr) was interrupted by a 900-bp insertion that
      corresponded to an incomplete member of a fourth mariner element, called Azteca.
      In this work, we isolate and characterize full-length Tnigmar-Az elements in T.
      nigerrimum. The purpose of this study is to clarify the evolutionary history of
      Azteca elements and their hosts as well as the possible existence of horizontal
      transfer processes. For this, Azteca-like elements were also retrieved from the
      available sequences of various ant genomes, representing four different ant
      subfamilies: Dolichoderinae, Formicinae, Myrmicinae, and Ponerinae. The tree
      topology resulting for the Azteca-like elements bore very little resemblance to
      that of their respective hosts. The pervasive presence of Azteca-like elements in
      all ant genomes, together with the observation that extant copies are usually
      younger than the genomes that host them, could be explained either by lineage
      sorting or by recent horizontal transfer of active elements. However, the finding
      of closer genetic relationships between elements than between the ants that host
      them is consistent with the latter scenario. This is clearly observed in Sinvmar
      Az, Tnigmar-Az, Acepmar-Az, and Cflomar-Az elements, suggesting the existence of
      horizontal transfer processes. On the contrary, some elements displayed more
      divergence than did the hosts harboring them. This may reflect either further
      horizontal transfer events or random lineage sorting. 

PMID- 26195137
TI  - Methyl-substitution of an iminohydantoin spiropiperidine beta-secretase (BACE-1)
      inhibitor has a profound effect on its potency.
AB  - The IC50 of a beta-secretase (BACE-1) lead compound was improved ~200-fold from
      11 MUM to 55 nM through the addition of a single methyl group. Computational
      chemistry, small molecule NMR, and protein crystallography capabilities were used
      to compare the solution conformation of the ligand under varying pH conditions to
      its conformation when bound in the active site. Chemical modification then
      explored available binding pockets adjacent to the ligand. A strategically placed
      methyl group not only maintained the required pKa of the piperidine nitrogen and
      filled a small hydrophobic pocket, but more importantly, stabilized the
      conformation best suited for optimized binding to the receptor.

PMID- 26195138
TI  - Decelerated vascularization in tissue-engineered constructs in association with
      diabetes mellitus in vivo.
AB  - AIMS: Rapid blood vessel ingrowth in transplanted tissue engineering constructs
      is the key factor for successful incorporation, but many potential patients who
      may use engineered tissues suffer from widespread diseases that limit the
      capacity of neovascularization (e.g. diabetes). Thus, in vivo vascularization
      analyses of tissue-engineered constructs in angiogenically affected organisms are
      required. METHODS: We therefore investigated the in vivo incorporation of
      collagen-coated and cell-seeded poly-L-lactide-co-glycolide scaffolds in diabetic
      B6.BKS(D)-Lepr(db)/J mice using repetitive intravital fluorescence microscopy
      over a time period of two weeks. For this purpose, scaffolds were seeded with
      osteoblast-like or bone marrow mesenchymal stem cells and implanted into the
      dorsal skinfold chambers of diabetic and non-diabetic (C57BL/6) mice. RESULTS:
      Apart from slightly increased inflammatory parameters, diabetic mice showed
      significantly reduced capillary densities compared with non-diabetic animals from
      day 6 onward. In line with previous studies, more densely meshed microvascular
      networks were demonstrated in cell-seeded than in collagen-coated scaffolds from
      day 6 onward within the single groups (diabetic and control). CONCLUSIONS: A
      large number of patients who suffer from systemic diseases that affect
      angiogenesis would profit from tissue engineering. Therefore, the challenge for
      the clinical introduction of tissue-engineered constructs will be to overcome the
      decreased angiogenesis in diabetic organisms.

PMID- 26195139
TI  - Tibial anatomy in normal small breed dogs including anisometry of various
      extracapsular stabilizing suture attachment sites.
AB  - OBJECTIVES: To investigate proximal tibial anatomy and its influence on
      anisometry of extracapsular stabilizing sutures in small dog breeds. MATERIALS
      AND METHODS: Mediolateral radiographs of the femora, stifles, and tibiae of 12
      small breed dogs were acquired with the stifles positioned at various angles.
      Measurements taken included tibial plateau angle (TPA), diaphyseal: proximal
      tibial angle (DPA), patellar tendon angle (PTA), Z-angle, relative tibial
      tuberosity width (rTTW), and the distance between six combinations of two femoral
      and three tibial extra-capsular stabilizing suture (ECS) attachment sites.
      Theoretical strain through stifle range-of-motion was recorded. RESULTS: The TPA
      (32 degrees  +/- 5.8 degrees ), DPA (10.2 degrees  +/- 7.3 degrees ), PTA (103.7
      degrees  +/- 6.2 degrees ), and Z-angle (70.4 degrees  +/- 9.0 degrees ) were
      positively correlated with one another (R >0.7), but none were correlated with
      rTTW (0.93 +/- 0.10). The F2-T1 combination of ECS attachment sites had lowest
      strain for nine stifles. The shortest attachment site separation was at a stifle
      flexion of 50 degrees  for nine stifles. Proximal tibial anatomy measurements
      could not predict optimal attachment site combination, optimal stifle angle for
      suture placement, or ECS strain. CLINICAL SIGNIFICANCE: There is individual
      variation in the optimal attachment site combination and stifle angle for suture
      placement, which may influence consistency of outcomes with ECS.

PMID- 26195140
TI  - Multiple C2 domains transmembrane protein 1 is expressed in CNS neurons and
      possibly regulates cellular vesicle retrieval and oxidative stress.
AB  - Multiple C2 domains transmembrane protein 1 (MCTP1) contains two transmembrane
      regions and three C2 domains of high Ca(2+)-binding affinity. Single-nucleotide
      polymorphism (SNP) of human MCTP1 gene is reportedly associated with bipolar
      disorder, but expression and function of MCTP1 in the CNS is still largely
      unknown. We cloned rat MCTP1 isoforms, and studied expression of MCTP1 transcript
      and protein in the CNS. Subcellular distribution and functional roles of MCTP1
      were investigated in cultured primary neurons or PC12 cells by over-expression,
      cell imaging, and flow cytometry. MCTP1 immunostaining was seen in both CNS
      neuronal cell bodies and processes, especially in the hippocampus, dentate gyrus,
      medial habenular nucleus, amygdala, and selected cerebral and cerebellar cortical
      areas/layers. Under an electron microscope, MCTP1 immunoreactivity was observed
      on vesicles in neuronal cell bodies and pre-synaptic axon terminals. In cultured
      primary neurons and PC12 cells MCTP1 was detected on selected populations of
      secretory vesicles and endosomes. MCTP1 over-expression significantly inhibited
      neuronal transferrin endocytosis, secretory vesicle retrieval, cell migration,
      and oxidative stress from glutamate toxicity. Thus MCTP1 might be involved in
      regulating endocytic recycling of specific CNS neurons and synapses. MCTP1
      abnormality might cause altered synaptic vesicle recycling, and thereby lead to
      vulnerability to neuropsychiatric diseases.

PMID- 26195142
TI  - Glomerular disease: TRPC6 and NPHS1 mediate FSGS risk.

PMID- 26195145
TI  - Therapy: Maintenance of steroid-free remission in nephrotic syndrome.

PMID- 26195147
TI  - Chronic kidney disease-mineral and bone disorder: Fracture burden in children
      with CKD.

PMID- 26195148
TI  - Ligand-induced conformation changes drive ATP hydrolysis and function in
      SMARCAL1.
AB  - Mutations and deletions in SMARCAL1, an SWI2/SNF2 protein, cause Schimke immuno
      osseous dysplasia (SIOD). SMARCAL1 preferentially binds to DNA molecules
      possessing double-stranded to single-stranded transition regions and mediates
      annealing helicase activity. The protein is critical for alleviating replication
      stress and maintaining genome integrity. In this study, we have analysed the
      ATPase activity of three mutations - A468P, I548N and S579L - present in SIOD
      patients. These mutations are present in RecA-like domain I of the protein.
      Analysis using active DNA-dependent ATPase A domain (ADAAD), an N-terminal
      deleted construct of bovine SMARCAL1, showed that all three mutants were unable
      to hydrolyse ATP. Conformational studies indicated that the alpha-helix and beta
      sheet content of the mutant proteins was altered compared to the wild-type
      protein. Molecular simulation studies confirmed that major structural changes had
      occurred in the mutant proteins. These changes included alteration of a loop
      region connecting motif Ia and II. As motif Ia has been implicated in DNA
      binding, ligand binding studies were done using fluorescence spectroscopy. These
      studies revealed that the Kd for protein-DNA interaction in the presence of ATP
      was indeed altered in the case of mutant proteins compared to the wild-type.
      Finally, in vivo studies were done to complement the in vitro and in silico
      studies. The results from these experiments demonstrate that mutations in human
      SMARCAL1 that result in loss in ATPase activity lead to increased replication
      stress and therefore possibly manifestation of SIOD.

PMID- 26195150
TI  - A Continuous Quality Improvement Project to Implement Infant-Driven Feeding as a
      Standard of Practice in the Newborn/Infant Intensive Care Unit.
AB  - OBJECTIVE: To increase the number of neonates who were fed according to cues
      prior to discharge and potentially decrease length of stay. DESIGN: Continuous
      quality improvement. SETTING: Eighty-five bed level IV neonatal intensive care
      unit. PATIENTS: Surgical and nonsurgical neonates of all gestational ages.
      Neonates younger than 32 weeks gestation, who required intubation, continuous
      positive airway pressure (CPAP), high flow nasal cannula (HFNC), or did not have
      suck or gag reflexes were excluded as potential candidates for infant-driven
      feeding. INTERVENTION/MEASUREMENTS: The project was conducted over a 13-month
      period using the following methods: (a) baseline data collection, (b) designation
      of Infant Driven Feeding (IDF) Champions, (c) creation of a multidisciplinary
      team, (d) creation of electronic health record documentation, (e) initial staff
      education, (f) monthly team meetings, (g) reeducation throughout the duration of
      the project, and (h) patient-family education. RESULTS: Baseline data were
      collected on 20 neonates with a mean gestational age of 36 0/7(th) weeks and a
      mean total length of stay (LOS) of 43 days. Postimplementation data were
      collected on 150 neonates with a mean gestational age of 36 1/7(th) weeks and a
      mean total LOS of 36.4 days. A potential decrease in the mean total LOS of stay
      by 6.63 days was achieved during this continuous quality improvement (CQI)
      project. CONCLUSIONS: Neonates who are fed according to cues can become
      successful oral feeders and can be safely discharged home regardless of
      gestational age or diagnosis.

PMID- 26195151
TI  - Refusing to imagine? On the possibility of psychogenic aphantasia. A commentary
      on Zeman et al. (2015).

PMID- 26195152
TI  - Implicit attention to negative social, in contrast to nonsocial, words in the
      Stroop task differs between individuals high and low in loneliness: Evidence from
      event-related brain microstates.
AB  - Being on the social perimeter is not only sad, it is dangerous. Our evolutionary
      model of the effects of perceived social isolation (loneliness) on the brain as
      well as a growing body of behavioral research suggests that loneliness promotes
      short-term self-preservation, including an increased implicit vigilance for
      social, in contrast to nonsocial, threats. However, this hypothesis has not been
      tested previously in a neuroimaging study. We therefore used high density EEG and
      a social Stroop interference task to test the hypothesis that implicit attention
      to negative social, in contrast to nonsocial, Words in the Stroop task differs
      between individuals high versus low in loneliness and to investigate the brain
      dynamics of implicit processing for negative social (vs nonsocial) stimuli in
      lonely individuals, compared to nonlonely individuals (N = 70). The present study
      provides the first evidence that negative social stimuli are differentiated from
      negative nonsocial stimuli more quickly in the lonely than nonlonely brains.
      Given the timing of this differentiation in the brain and the fact that
      participants were performing a Stroop task, these results also suggest that these
      differences reflect implicit rather than explicit attentional differences between
      lonely and nonlonely individuals. Source estimates were performed for purposes of
      hypothesis generation regarding underlying neural mechanisms, and the results
      implicated the neural circuits reminiscent of orienting and executive control
      aspects of attention as contributing to these differences. Together, the results
      are in accord with the evolutionary model of loneliness.

PMID- 26195153
TI  - Patterns of frontoparietal activation as a marker for unsuccessful visuospatial
      processing in healthy aging.
AB  - Visuospatial abilities are sensitive to age-related decline, although the neural
      basis for this decline (and its everyday behavioral correlates) is as yet poorly
      understood. fMRI was employed to examine age-related differences in patterns of
      functional activation that underlie changes in visuospatial processing. All
      participants completed a brief neuropsychological battery and also a figure
      ground task (FGT) assessing visuospatial processing while fMRI was recorded.
      Participants included 16 healthy older adults (OA; aged 69-82 years) and 16
      healthy younger adults (YA; aged 20-35 years). We examined age-related
      differences in behavioral performance on the FGT in relation to patterns of fMRI
      activation. OA demonstrated reduced performance on the FGT task and showed
      increased activation of supramarginal parietal cortex as well as increased
      activation of frontal and temporal regions compared to their younger
      counterparts. Performance on the FGT related to increased supramarginal gyrus
      activity and increased medial prefrontal activity in OAs, but not YAs. Our
      results are consistent with an anterior-posterior compensation model. Successful
      FGT performance requires the perception and integration of multiple stimuli and
      thus it is plausible that healthy aging may be accompanied by changes in
      visuospatial processing that mimic a subtle form of dorsal simultanagnosia.
      Overall, decreased visuospatial processing in OA relates to an altered
      frontoparietal neurobiological signature that may contribute to the general
      phenomenon of increasingly fragmented execution of behavior associated with
      normal aging.

PMID- 26195154
TI  - Supramolecular quantum dots as biodegradable nano-probes for upconversion-enabled
      bioimaging.
AB  - We report the biodegradable supramolecular quantum dots (SQDs) of hydrogen-bonded
      graphitic carbon nitride (g-C3N4) with low cytotoxicity and desirable
      biocompatibility for promising upconversion-enabled fluorescent bio-probes. A
      remarkable biodegradation of up to 97% within 24 hours is presented. 

PMID- 26195155
TI  - Autoimmune haemolytic anaemia occurring during ibrutinib therapy for chronic
      lymphocytic leukaemia--response to Rider et al.

PMID- 26195156
TI  - Unusual prolongation of radiation-induced G2 arrest in tumor xenografts derived
      from HeLa cells.
AB  - The effect of ionizing radiation on cell cycle kinetics in solid tumors remains
      largely unknown because of technical limitations and these tumors' complicated
      structures. In this study, we analyzed intratumoral cell cycle kinetics after X
      irradiation of tumor xenografts derived from HeLa cells expressing the
      fluorescent ubiquitination-based cell cycle indicator (Fucci), a novel system to
      visualize cell cycle kinetics in vivo. Cell cycle kinetics after X-irradiation
      was examined by using tumor sections and in vivo real-time imaging system in
      tumor xenografts derived from HeLa cells expressing Fucci. We found that G2
      arrest was remarkably prolonged, up to 5 days after 10-Gy irradiation, in
      contrast to monolayer cultures where G2 arrest returned within 24 h. Cells
      isolated from tumors 5 days after irradiation exhibited a higher surviving
      fraction than those isolated immediately or one day after irradiation. In this
      study, we clearly demonstrated unusual post-irradiation cell cycle kinetics in
      tumor xenografts derived from HeLa-Fucci cells. Our findings imply that prolonged
      G2 arrest occurring in tumor microenvironments following irradiation may function
      as a radioresistance mechanism.

PMID- 26195157
TI  - Intrapulmonary Solitary Fibrous Tumors: Benign or Malignant?

PMID- 26195158
TI  - Impact of rurality on maternal and infant health indicators and outcomes in
      Maine.
AB  - INTRODUCTION: Rural residents may face health challenges related to geographic
      barriers to care, physician shortages, poverty, lower educational attainment, and
      other demographic factors. In maternal and child health, these disparities may be
      evidenced by the health risks and behaviors of new mothers, the health of infants
      born to these mothers, and the care received by both mothers and infants.
      METHODS: To determine the impact of rurality on maternal and child health in
      Maine, USA, 11 years of data (2000-2010) for the state of Maine from the
      Pregnancy Risk Assessment Monitoring System (PRAMS) project were analyzed. PRAMS
      is a national public health surveillance system that uses questionnaires to
      survey women who had delivered live infants in the previous 2-4 months. Using a
      geographic information system, each questionnaire response was assigned a
      rurality tier (urban, suburban, large rural town, or isolated rural community)
      based on the rural-urban commuting area code of the town of residence of the
      mother. Results from the four rurality tiers were compared using the survey
      procedures in Statistical Analysis Software to adjust for the complex sampling
      strategy of the PRAMS dataset. Means (for continuous variables) and percentages
      (for categorical variables) were calculated for each rurality tier, along with
      95% confidence intervals. Significant differences between rurality tiers were
      tested for using F-tests or chi2 tests. If significant differences between
      rurality tiers existed (p<0.05), specific tiers were judged to be different from
      each other if their 95% confidence intervals did not overlap. RESULTS: A total of
      12 600 mothers responded to the PRAMS questionnaire during the study period.
      Compared to mothers from more urban areas, rural mothers were younger (10.5% of
      mothers from isolated rural areas were teenagers compared to 6.2% of mothers from
      urban areas), less well educated, less likely to be married, and more likely to
      live in lower income households (39.6% of isolated rural mothers had household
      incomes <=US$20 000/year vs 28.8% of urban mothers). Rural mothers had higher pre
      pregnancy body mass indexes (BMIs; average BMI 26.1 for isolated rural women vs
      25.3 for urban women) and were more likely to smoke but less likely to drink
      alcohol (both before and during pregnancy). Compared to mothers from more urban
      areas, rural mothers were not sure they were pregnant until a later gestational
      age but received prenatal care just as early and were just as likely to receive
      prenatal care as early as they wished. There were no differences among rurality
      tiers in Caesarean section rates, rates of premature births (<37 weeks
      gestation), or rates of underweight births (<2500 g). However infants born to
      rural mothers were less likely to be breastfed (52.9% of isolated rural vs 60.9%
      of urban infants breast fed for >=8 weeks). CONCLUSIONS: These results show that,
      while rural women face significant demographic and behavior challenges, their
      access to prenatal care, the care they receive while pregnant, and the outcomes
      of their pregnancies are similar to those of urban women. These results highlight
      areas where focused pre-pregnancy and prenatal education may improve maternal and
      child health in rural Maine.

PMID- 26195159
TI  - Editorial Comment from Dr Schiavina and Dr Borghesi to Postoperative prostate
      specific antigen monitoring interval for radical prostatectomy patients with low
      recurrence risk.

PMID- 26195160
TI  - Ninety-Day Subchronic Oral Toxicity Study of Senecio scandens Extract in Rats.
AB  - The present study assessed the safety/toxicity of Senecio scandens, a well-known
      Chinese herb that is used as an anti-inflammatory, antibiosis, and antipyretic
      drug. A 90-d subchronic oral toxicity study of S. scandens was performed in
      Wistar rats. The extract of S. scandens was administered orally to male and
      female rats at a single dose of 225, 450, and 900 mg/kg/d. There was no obvious
      toxicity. Certain changes in hematology and coagulation parameters (red cell
      distribution width (RDW), platelet count (PLT), monocyte percentage (Mo%),
      activated partial thromboplastin time (APTT), prothrombin time (PT)) were
      observed in some administration groups. In regards to the blood biochemical
      parameters, the levels of creatinine (CRN), potassium, and chloride were
      increased in a number of the treated rats. There were no significant changes in
      other hematology, coagulation, or biochemical parameters in rats orally
      administered S. scandens. S. scandens has a slight effect on rat coagulation and
      metabolism systems. The herb was safe at all doses tested, but caution should be
      taken when administering S. scandens at higher doses. 

PMID- 26195162
TI  - Erratum to: Excitability of the infraspinatus, but not the middle deltoid, is
      affected by shoulder elevation angle.

PMID- 26195161
TI  - An Efficient Genome-Wide Fusion Partner Screening System for Secretion of
      Recombinant Proteins in Yeast.
AB  - To produce rarely secreted recombinant proteins in the yeast Saccharomyces
      cerevisiae, we developed a novel genome-wide optimal translational fusion partner
      (TFP) screening system that involves recruitment of an optimal secretion signal
      and fusion partner. A TFP library was constructed from a genomic and truncated
      cDNA library by using the invertase-based signal sequence trap technique. The
      efficiency of the system was demonstrated using two rarely secreted proteins,
      human interleukin (hIL)-2 and hIL-32. Optimal TFPs for secretion of hIL-2 and hIL
      32 were easily selected, yielding secretion of these proteins up to hundreds of
      mg/L. Moreover, numerous uncovered yeast secretion signals and fusion partners
      were identified, leading to efficient secretion of various recombinant proteins.
      Selected TFPs were found to be useful for the hypersecretion of other recombinant
      proteins at yields of up to several g/L. This screening technique could provide
      new methods for the production of various types of difficult-to-express proteins.

PMID- 26195163
TI  - Mathematical impairment associated with high-contrast abnormalities in change
      detection and magnocellular visual evoked response.
AB  - The cause of developmental dyscalculia, a specific deficit in acquisition of
      arithmetic skills, particularly of enumeration, has never been investigated with
      respect to the patency of the visual magnocellular system. Here, the question of
      dysfunction of the afferent magnocellular cortical input and its dorsal stream
      projections was tested directly using nonlinear analysis of the visual evoked
      potential (VEP) and through the psychophysical ability to rapidly detect visual
      change. A group of young adults with self-reported deficiencies of arithmetical
      ability, showed marked impairment in magnitude estimation and enumeration
      performance-though not in lexical decision reaction times when compared with an
      arithmetically capable group controlled for age and handedness. Multifocal
      nonlinear VEPs were recorded at low (24 %) and high (96 %) contrast. First- and
      second-order VEP kernels were comparable between groups at low contrast, but not
      at high contrast. The mathematically impaired group showed an abnormal lack of
      contrast saturation in the shortest latency first-order peak (N60) and a delayed
      P100 positivity in the first slice of the second-order kernel. Both features have
      previously been argued to be physiological markers of magnocellular function.
      Mathematically impaired participants also performed worse on a gap paradigm
      change detection for digit task showing increased reaction times for high
      contrast stimuli but not for low-contrast stimuli compared with controls. The VEP
      results give direct evidence of abnormality in the occipital processing of
      magnocellular information in those with mathematical impairment. The anomalous
      high visual contrast physiological and psychophysical performance suggests an
      abnormality in the inhibitory processes that normally result in saturation of
      contrast gain in the magnocellular system.

PMID- 26195165
TI  - Comment on Iodice P, Cesinaro S, Romani GL, Pezzulo G: More gain less pain:
      balance control learning shifts the activation patterns of leg and neck muscles
      and increases muscular parsimony.

PMID- 26195164
TI  - Chronic deep brain stimulation of the medial forebrain bundle reverses depressive
      like behavior in a hemiparkinsonian rodent model.
AB  - Preclinical and clinical evidence suggests that depression might be associated
      with a dysfunction in the reward/motivation circuitry. Deep brain stimulation
      (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has been
      shown in a recent clinical trial to provide a prompt and consistent improvement
      of depressive symptoms in treatment-resistant patients. In order to better
      understand the underlying mechanisms of neuromodulation in the context of
      depression, the effects of chronic bilateral MFB-DBS were assessed in a combined
      rodent model of depression and Parkinson's disease. Female Sprague-Dawley rats
      received unilateral 6-OHDA injection in the right MFB and were divided into three
      groups: CMS-STIM, CMS-noSTIM and control group. The CMS groups were submitted to
      chronic unpredictable mild stress (CMS) protocol for 6 weeks. MFB-DBS was applied
      only to the CMS-STIM group for 1 week. All groups were repeatedly probed on a
      series of behavioral tasks following each intervention, and to a postmortem
      histological analysis. CMS led to an increase in immobility in the forced swim
      test, to a decrease in sucrose solution consumption in the sucrose preference
      test, as well as to an increased production of ultrasonic vocalizations in the 22
      kHz range, indicating increased negative affect. MFB-DBS reversed the anhedonic
      like and despair-like behaviors. The results suggest that unilateral dopamine
      depletion did not preclude MFB-DBS in reversing depressive-like and anhedonic
      like behavior in the rodent. Further understanding of the importance of
      hemispheric dominance in neuropsychiatric disorders is essential in order to
      optimize stimulation as a therapeutic strategy in these diseases. 

PMID- 26195166
TI  - Anticipatory and compensatory postural adjustments in conditions of body
      asymmetry induced by holding an object.
AB  - The effect of body asymmetry on anticipatory and compensatory postural
      adjustments was studied. Ten healthy subjects stood on the force platform and
      held an object in one hand which induced body asymmetry. Subjects were exposed to
      external perturbations applied to their shoulders while standing with either
      normal or narrow base of support. Bilateral electromyographic activity (EMG) of
      dorsal and ventral trunk and leg muscles and center-of-pressure displacements
      were recorded. Data was analyzed within the intervals typical for anticipatory
      (APA) and compensatory postural adjustments. Integrals of EMG activity and co
      contraction and reciprocal activation of muscles were calculated and analyzed.
      Reciprocal activation of muscles on the target side and co-contraction of muscles
      on the contralateral side were seen when standing in asymmetrical stance and
      being subjected to external perturbations. Decreased magnitudes of co-contraction
      and reciprocal activation of muscles were seen in the APA phase while standing
      asymmetrically with narrow base of support. The findings highlight the importance
      of investigating the role of body asymmetry in maintaining control of vertical
      posture. The outcome of the study provides a foundation for future studies
      focusing on improvement in postural control in individuals with body asymmetry
      due to unilateral weakness. 

PMID- 26195167
TI  - Online processing of shape information for control of grasping.
AB  - When picking up objects, we tend to grasp at contact points that minimize
      slippage and torsion, which depend on the particular shape. Normally, grasp
      points could be planned before initiating movement. We tested whether grasp
      points can be determined during online control. Subjects reached to grasp virtual
      planar objects with varied shapes. On some trials, the object was changed during
      movement, either rotated by 45 degrees  or replaced with a different object. In
      all conditions, grasp axes were well adapted to the target shape, passing near
      the center of mass with low force closure angles. On perturbed trials, corrective
      adjustments were detectable within 320 ms and were toward the same grasp axes
      observed on unperturbed trials. Perturbations had little effect on either
      kinematics or the optimality of final grasp points. Our results demonstrate that
      the visuomotor system is capable of online processing of shape information to
      determine appropriate contact points for grasping. 

PMID- 26195168
TI  - Shining new light on dark percepts: visual sensations induced by TMS.
AB  - Phosphenes induced by transcranial magnetic stimulation (TMS) are sensations of
      light, whereas a missing region in the visual field induced by TMS is generally
      referred to as a scotoma. It is believed that phosphenes are caused by neural
      excitation, while scotomas are due to neural inhibition. In light of the recent
      literature it might, however, be surmised that both phenomena are the result of
      neural noise injected into the cortex by TMS and that the likelihood of
      perceiving the two kinds of percepts depends on the state of the cortex at the
      time of stimulation. In the present study, TMS was applied over the left
      occipital cortex under different background conditions (Experiments 1-2) and
      using different TMS intensities (Experiment 3). Behavioral responses indicate the
      visual system processes luminance in a standardized manner, as lighter percepts
      were reacted to faster than darker percepts; this effect, however, did not extend
      to percept size. Our results suggest that phenomenological characteristics of
      artificial visual percepts are in line with the proposed effects of TMS as the
      induction of random neural noise interfering with the neural dynamics (the state
      of the cortex) at the time of stimulation. 

PMID- 26195169
TI  - Early attenuation of long-term potentiation in senescence-accelerated mouse prone
      8.
AB  - Senescence-accelerated mouse (SAM) is an experimental model animal showing a
      short lifespan and rapid advancement of senescence. Especially, SAM prone 8
      (SAMP8) shows age-related impairment of learning and memory, and thus, it is a
      good model for age-related cognitive function. However, the synaptic
      characteristics related to cognitive function of SAMP8 have been poorly
      understood. In this study, we quantitatively evaluated the synaptic transmission
      and synaptic plasticity using hippocampal slices obtained from SAMP8 with
      electrophysiological methods to elucidate the synaptic features of SAMP8. We used
      the field recordings to measure some synaptic parameters. The slope of field
      excitatory postsynaptic potentials decreased with age in both SAMP8 and SAM
      resistant 1 (SAMR1), the control strain of SAMP8. The paired-pulse ratio (PPR), a
      representative of short-term synaptic plasticity, also decreased in both strains
      with age. On the other hand, although both SAMR1 and SAMP8 exhibited age
      dependent decrease in long-term potentiation (LTP), a representative of long-term
      synaptic plasticity, the decrease in LTP in SAMP8 started at 6 months of age,
      while in SAMR1, it was observed at 14 months but not at 6 months of age. The PPRs
      after high-frequency stimulation for LTP induction were smaller than those before
      the stimulation. These results indicate that synaptic plasticity in SAMP8
      deteriorates at an earlier age compared to SAMR1, and are consistent with
      behavioral tests showing early impairment of learning and memory of SAMP8. Our
      study is the first report on quantitative analysis of synaptic function at SAMP8
      hippocampus and corroborates the behavioral studies showing cognitive dysfunction
      with age; therefore, it will be helpful for future studies on aging. 

PMID- 26195170
TI  - Multisensory distortions of the hand have differential effects on tactile
      perception.
AB  - Research has suggested that altering the perceived shape and size of the body
      image significantly affects perception of somatic events. The current study
      investigated how multisensory illusions applied to the body altered tactile
      perception using the somatic signal detection task. Thirty-one healthy volunteers
      were asked to report the presence or absence of near-threshold tactile stimuli
      delivered to the index finger under three multisensory illusion conditions:
      stretched finger, shrunken finger and detached finger, as well as a veridical
      baseline condition. Both stretching and shrinking the stimulated finger enhanced
      correct touch detections; however, the mechanisms underlying this increase were
      found to be different. In contrast, the detached appearance reduced false touch
      reports-possibly due to reduced tactile noise, as a result of attention being
      directed to the tip of the finger only. These findings suggest that distorted
      representations of the body could have different modulatory effects on attention
      to touch and provide a link between perceived body representation and
      somatosensory decision-making. 

PMID- 26195172
TI  - General Formation of M(x)Co(3-x)S4 (M=Ni, Mn, Zn) Hollow Tubular Structures for
      Hybrid Supercapacitors.
AB  - A simple and versatile method for general synthesis of uniform one-dimensional
      (1D) M(x)Co(3-x)S4 (M=Ni, Mn, Zn) hollow tubular structures (HTSs), using soft
      polymeric nanofibers as a template, is described. Fibrous core-shell polymer@M-Co
      acetate hydroxide precursors with a controllable molar ratio of M/Co are first
      prepared, followed by a sulfidation process to obtain core-shell polymer@M(x)Co(3
      x)S4 composite nanofibers. The as-made M(x)Co(3-x)S4 HTSs have a high surface
      area and exhibit exceptional electrochemical performance as electrode materials
      for hybrid supercapacitors. For example, the MnCo2S4 HTS electrode can deliver
      specific capacitance of 1094 F g(-1) at 10 A g(-1), and the cycling stability is
      remarkable, with only about 6% loss over 20,000 cycles.

PMID- 26195171
TI  - Intersegmental coordination scales with gait speed similarly in men and women.
AB  - We applied principal component analysis (PCA) to thigh, shank, and foot elevation
      angles to examine the impact of speed on intra-limb coordination during gait. The
      specific aims were to (1) determine speed-related changes in segment loadings on
      three principal components (PCs) and (2) examine differences between men and
      women. The subjects (26 women, 21 men) walked overground at five self-selected
      paces (very slow, slow, normal, fast, very fast). PCA yielded percent variation
      (PV) explained by each PC and thigh, shank, and foot loadings on PC1-PC3. These
      parameters were regressed against the speed normalized to body height (BH/s) to
      derive individual and aggregate slopes and P values, separately for men and
      women. PV1 increased with speed, whereas PV2 and PV3 decreased (all P < 0.001).
      The loadings of thigh and foot segments on PC1 increased with speed (0.14 and
      0.04 per BH/s, P < 0.001, respectively), and the loading of shank decreased (
      0.10, P < 0.001). Compared to PC1, the changes in segment loadings on PC3 were
      the opposite (thigh -0.18, shank 0.09, foot -0.04 per BH/s, P < 0.001). The
      changes in segment loadings on PC2 were inconsistent and generally small. The
      only significance (P = 0.006), albeit a minor difference between men and women,
      was in the slope of thigh loading on PC2 (-0.005 +/- 0.019 and 0.015 +/- 0.026
      per BH/s, respectively). We conclude that intersegmental coordination during gait
      scales with speed, with the greatest impact on the thigh segment, but no
      differently between men and women. 

PMID- 26195174
TI  - Deep Brain Stimulation for Major Depression-Steps on a Long and Winding Road.

PMID- 26195173
TI  - Use of Decision Support for Improved Knowledge, Values Clarification, and
      Informed Choice in Patients With Rheumatoid Arthritis.
AB  - OBJECTIVE: To examine the potential value of a theory-based, interactive decision
      support tool in clinical practice for patients with rheumatoid arthritis who are
      candidates for biologic agents. METHODS: We conducted an 8-week, 2-arm, parallel,
      single-blind pilot trial in which candidates for treatment escalation with a
      biologic agent were randomized to receive either a link to a web-based tool or
      usual care. Outcomes included changes in objective knowledge, subjective
      knowledge, values clarification, and satisfaction with risk communication as well
      as the proportion of subjects defined as making an informed choice to escalate
      care at 2 weeks. RESULTS: A total of 125 subjects were randomized. Significant
      between-group differences at 2 weeks favoring the intervention group were seen
      for changes in objective knowledge, subjective knowledge, and values
      clarification. No significant between-group differences were found in subjects'
      satisfaction with risk communication. Among those deciding to escalate care, a
      greater percentage met the criteria for an informed choice at 2 weeks in the
      intervention group compared to the control group (32% versus 13%; P = 0.02).
      Improvements in subjective knowledge and values clarification persisted at 8
      weeks. There were no between-group differences in objective knowledge at 8 weeks.
      CONCLUSION: In this study, use of a decision support tool at the time of decision
      making resulted in improved objective and subjective knowledge, as well as values
      clarity, compared to usual care. Not all improvements were sustained, emphasizing
      the need to offer educational support should additional escalation of care be
      required over the course of the illness.

PMID- 26195175
TI  - Circadian Rhythms and Psychopathology: From Models of Depression to Rhythms in
      Clock Gene Expression and Back Again.

PMID- 26195176
TI  - Erythropoietin as an Innovative Add-on Therapy for Depression.

PMID- 26195177
TI  - Evaluation of the impact of Brazil's sustainability on the behavioral intentions
      of stakeholders toward the country.
AB  - This paper examines the influence of sustainability as a dimension of country
      image on behavioral intentions (so-called conations) of stakeholders toward
      Brazil. In addition, sustainable consumption, a moderating variable of the
      country-of-origin effect (not been identified in other studies), and consumers'
      gender and familiarity with the country are investigated as moderating variables.
      The empirical research is of a descriptive nature, and in terms of data
      collection, a survey method has been used on a sample of undergraduate students
      from foreign institutions. In total, 427 questionnaires have been considered in
      the analysis. The results of a multiple regression analyses show that the
      dimensions of country image (affective, political, technical and sustainability)
      are reliable factors that have a positive influence on conations toward Brazil,
      with the affective dimension exerting the strongest influence. Further
      comparisons show that the sustainability dimension is more important in shaping
      the conations of female respondents and those with low familiarity with Brazil,
      whereas the political dimension is more relevant in shaping the conations of male
      respondents and those with high familiarity with Brazil. Finally, the
      sustainability dimension has a minor influence on individuals with higher levels
      of sustainable consumption. 

PMID- 26195178
TI  - Efficacy of colchicine in a child with relapsing bullous Henoch-Schonlein
      purpura.
AB  - Colchicine is not usually considered a treatment option for cutaneous lesions of
      Henoch-Schonlein purpura (HSP) in children. We report a case of pediatric HSP
      with severe chronic and relapsing cutaneous manifestations that were resistant to
      corticosteroids. Colchicine had remarkable therapeutic efficacy, with positive
      dechallenge and rechallenge, without any adverse effects. CONCLUSION: Colchicine
      should be considered for chronic, severe cutaneous lesions of pediatric HSP. WHAT
      IS KNOWN: Colchicine is not usually considered a treatment option for cutaneous
      lesions of Henoch-Schonlein purpura (HSP) in children. What is New: We report a
      case of pediatric HSP with severe cutaneous manifestations that responded well to
      colchicine. Colchicine should be considered for chronic cutaneous lesions of HSP
      in children.

PMID- 26195179
TI  - Health Insurance Paid Costs and Drivers of Costs for Patients With Crohn's
      Disease in the United States.
AB  - OBJECTIVES: The cost of medical care for Crohn's disease (CD) and comorbidities
      in the era of biologics is unclear. We examined insurance claims data from US
      health plans to understand this relationship. METHODS: Longitudinal CD patient
      data and reimbursement information from 11 health plans engaged with Accordant
      Health Services between 2011 and 2013 were analyzed. The analysis considered data
      for all CD patients and for the patient subgroup <=20 years and >20 years of age.
      Descriptive statistics measured the mean health-plan paid costs per patient, the
      relative cost contribution of anti-tumor necrosis factor (TNF) agents, and health
      care costs for 31 specific comorbid conditions among CD patients. RESULTS:
      Overall, there were 5,090 CD patients (57% women) of which 587 CD patients were
      <=20 years of age. The mean health-plan paid cost per member per year was $18,637
      (s.d. $32,023) for all CD patients, $22,796 (s.d. $ 41,905) for CD patients <=20
      years, and $18,095 (s.d. $30,065) for patients >20 years of age. Twenty-eight
      percent of CD patients accounted for 80% of total costs. No differences were
      found in costs based on gender. Increased health-plan paid costs were
      significantly correlated with the number of comorbid conditions across all ages.
      Pharmacy utilization costs account for nearly one-half (45.5%) of the total CD
      attributable costs, exceeding inpatient care costs. Anti-TNF agents alone
      comprised nearly one-third (29.5%) of total costs. Aside from anti-TNF costs,
      other major categories of expense were as follows: inpatient 23.1%, outpatient
      hospital setting 15.7%, and MD office 8.2%. CONCLUSIONS: Total health-care costs
      in CD exceed previous estimates, with the majority of costs being allocated to a
      relatively small subgroup of patients. Pharmacy utilization costs, owing to anti
      TNF use, result in increasing total health-care costs and currently exceed costs
      for inpatient care. Pragmatic strategies to encourage gastroenterologists in the
      best clinical practice of optimizing anti-TNF use-in particular for younger age
      patients and those with multiple comorbidities-are necessary to reduce avoidable
      pharmacy utilization and inpatient care costs.

PMID- 26195180
TI  - Impact of statin use on survival in patients undergoing resection for early-stage
      pancreatic cancer.
AB  - OBJECTIVES: It has been suggested that statins exert potential anti-tumor
      effects. The relationship between statin use and outcomes in pancreatic cancer is
      controversial. We hypothesized that statin use at baseline would impact survival
      among patients with early-stage pancreatic cancer and that the effect might vary
      by individual statin agent. METHODS: We conducted a retrospective cohort study on
      data from an integrated healthcare system. We included patients with pancreatic
      cancer stage I-IIb who underwent resection for curative intent between January
      2005 and January 2011. Baseline statin use was characterized as any prior use as
      well as active use of either simvastatin or lovastatin. Intensity of exposure was
      calculated as average daily dose prior to surgery. Overall and disease-free
      survival was assessed from surgery until the end of study (April 2014). We used
      the Kaplan-Meier method and Cox proportional hazards regression to evaluate the
      impact of baseline statin use on survival, adjusting for age, sex, Charlson
      comorbidity score, resection margin, disease stage, and receipt of adjuvant
      chemotherapy. RESULTS: Among 226 patients, 71 (31.4%) had prior simvastatin use
      and 27 (11.9%) had prior lovastatin use at baseline. Prior simvastatin but not
      lovastatin use was associated with improved survival (median 28.5 months (95%
      confidence limit (CL) 20.8, 38.4) for simvastatin vs. 12.9 months (9.6, 15.5) for
      lovastatin vs. 16.5 months (14.1, 18.9) for non-statin users; log-rank P=0.0035).
      In Cox regression, active simvastatin use was independently associated with
      reduced risk for mortality (adjusted hazard ratio (HR) 0.56 (95% CL 0.38, 0.83),
      P=0.004) and risk for recurrence (adjusted HR 0.61 (0.41, 0.89), P=0.01).
      Survival improved significantly among patients who received moderate-high
      intensity (median 42.1 months (24.0,52.7)) doses compared with those who received
      low-intensity doses of simvastatin (median 14.1 months (8.6, 23.8), log-rank
      P=0.03). CONCLUSIONS: The effects of statins varied by agent and dose. Active use
      of moderate-high-dose simvastatin at baseline was associated with improved
      overall and disease-free survival among patients undergoing resection for
      pancreatic cancer.

PMID- 26195182
TI  - Eliminating material constraints for nonlinearity with plasmonic metamaterials.
AB  - Nonlinear optical materials comprise the foundation of modern photonics, offering
      functionalities ranging from ultrafast lasers to optical switching, harmonic and
      soliton generation. Optical nonlinearities are typically strong near the
      electronic resonances of a material and thus provide limited tuneability for
      practical use. Here we show that in plasmonic nanorod metamaterials, the Kerr
      type nonlinearity is not limited by the nonlinear properties of the constituents.
      Compared with gold's nonlinearity, the measured nonlinear absorption and
      refraction demonstrate more than two orders of magnitude enhancement over a broad
      spectral range that can be engineered via geometrical parameters. Depending on
      the metamaterial's effective plasma frequency, either a focusing or defocusing
      nonlinearity is observed. The ability to obtain strong and fast optical
      nonlinearities in a given spectral range makes these metamaterials a flexible
      platform for the development of low-intensity nonlinear applications. 

PMID- 26195181
TI  - Cumulative incidence of, risk factors for, and outcome of dermatological
      complications of anti-TNF therapy in inflammatory bowel disease: a 14-year
      experience.
AB  - OBJECTIVES: The broader and prolonged use of anti-tumor necrosis factor (TNF)
      agents in inflammatory bowel disease (IBD) could expose patients to an increased
      risk of adverse reactions, including dermatological complications. We assessed
      the cumulative incidence of anti-TNF-induced cutaneous adverse reactions in IBD
      patients, their risk factors, their dermatological management, and their outcome
      in a large cohort of IBD patients. METHODS: In a single-center observational
      retrospective study, including all consecutive adult IBD patients treated with an
      anti-TNF agent between 2001 and 2014, all patients with dermatological
      complications under anti-TNF therapy were identified in a well-defined cohort of
      IBD patients. We conducted a survival analysis to determine the cumulative
      incidence of dermatological complications and risk factors for developing any
      dermatological complications, cutaneous infections, and psoriasiform lesions.
      Survival curves were estimated by the Kaplan-Meier method, and we used a Cox
      proportional hazards model to test the association between parameters and time to
      each event: any dermatological complication, cutaneous infections, and psoriasis
      lesions. RESULTS: Among 583 IBD patients, 176 dermatological complications
      occurred, involving 20.5% of patients. Median duration of follow-up was 38.2
      months (range: 1-179). Psoriasiform lesions (10.1%; 59/583) and cutaneous
      infections (11.6%, 68/583) were the most frequently observed, with a cumulative
      incidence of, respectively, 28.9% and 17.6% at 10 years. They led to anti-TNF
      discontinuation, respectively, in 18.6% and 2.9% of patients. In case of
      switching to another anti-TNF agent for psoriasiform lesions, recurrence occurred
      in 57% of patients. Ulcerative colitis was associated with a lower risk of
      developing cutaneous infections than Crohn's disease (hazard ratio (HR)=0.25; 95%
      confidence interval (CI)=0.09-0.68; P=0.007). Higher dosing of anti-TNF agent was
      associated with a higher risk of developing cutaneous infections (HR=1.99; 95%
      CI=1.09-3.64; P=0.025). A younger age at time of anti-TNF initiation was
      associated with a higher risk of dermatological complications (HR=2.25; 95%
      CI=1.39-3.62; P<0.001). CONCLUSIONS: Dermatological complications involve one of
      five patients treated with anti-TNF therapy after a 14-year follow-up.
      Association of cutaneous infections with higher anti-TNF dosing suggests a dose
      dependent effect. Discontinuation of anti-TNF therapy due to dermatological
      complications is required in one out of five patients with psoriasiform lesions,
      but specific dermatological treatment allows to continue anti-TNF therapy in half
      of them.

PMID- 26195185
TI  - Muscle synergies: input or output variables for neural control?

PMID- 26195183
TI  - A Robust e-Epidemiology Tool in Phenotyping Heart Failure with Differentiation
      for Preserved and Reduced Ejection Fraction: the Electronic Medical Records and
      Genomics (eMERGE) Network.
AB  - Identifying populations of heart failure (HF) patients is paramount to research
      efforts aimed at developing strategies to effectively reduce the burden of this
      disease. The use of electronic medical record (EMR) data for this purpose is
      challenging given the syndromic nature of HF and the need to distinguish HF with
      preserved or reduced ejection fraction. Using a gold standard cohort of manually
      abstracted cases, an EMR-driven phenotype algorithm based on structured and
      unstructured data was developed to identify all the cases. The resulting
      algorithm was executed in two cohorts from the Electronic Medical Records and
      Genomics (eMERGE) Network with a positive predictive value of >95 %. The
      algorithm was expanded to include three hierarchical definitions of HF (i.e.,
      definite, probable, possible) based on the degree of confidence of the
      classification to capture HF cases in a whole population whereby increasing the
      algorithm utility for use in e-Epidemiologic research.

PMID- 26195186
TI  - Pathways to suicide attempts among male offenders: the role of agency.
AB  - Suicide is common among offenders, who are at increased risk of homelessness,
      unemployment and mental illness and are prone to impulsivity. Release from prison
      is a particularly vulnerable time. This qualitative study investigated the views
      of 35 offenders in South-West England prior to and after release from prison,
      enquiring into their previous suicide attempts and how they saw their future.
      Semi-structured interviews were analysed thematically, comparing individuals who
      had made one, more than one, and no suicide attempts. Multiple attempters were
      often in despair and enmeshed in substance misuse, with little control over their
      lives. Most of those with one-off or no previous attempts portrayed themselves as
      having more mastery. One-off attempters described using particularly violent
      means. The role of different types of agency in pathways to and from suicide is
      discussed. Iterational agency, the selective reactivation of past patterns of
      behaviour, appeared to dominate in individuals who were choosing between further
      suicide attempts and substance use. Projective agency, having a more future
      orientation, appeared more prominent in some single attempters and in those
      individuals with plans to escape crime and social exclusion. 

PMID- 26195184
TI  - Liraglutide improves carotid intima-media thickness in patients with type 2
      diabetes and non-alcoholic fatty liver disease: an 8-month prospective pilot
      study.
AB  - OBJECTIVE: To explore the effects of the glucagon-like peptide-1 receptor
      analogue liraglutide on subclinical atherosclerosis in diabetic subjects with non
      alcoholic fatty liver disease (NAFLD). RESEARCH DESIGN AND METHODS: In this 8
      month prospective study, 29 subjects with type 2 diabetes (T2DM) and NAFLD (16
      men and 13 women, mean age: 61 +/- 10 years) were matched for age and gender with
      29 subjects with T2DM without NAFLD (16 men and 13 women, mean age: 61 +/- 8
      years). Liraglutide 0.6 mg/day for 2 weeks, followed by 1.2 mg/day, was given in
      addition to metformin. MAIN OUTCOME MEASURES: Anthropometric variables,
      glucometabolic parameters and carotid intima-media thickness (IMT) using B-mode
      real-time ultrasound were assessed at baseline and 4 and 8 months. RESULTS:
      Glycated hemoglobin reduced significantly in both groups. No significant changes
      were found in body weight, waist circumference and lipids. Carotid IMT decreased
      significantly in the T2DM patients with NAFLD (from 0.96 +/- 0.27 to 0.82 +/-
      0.17 to 0.85 +/- 0.12 mm, p = 0.0325), but not in the T2DM patients without NAFLD
      (from 0.91 +/- 0.23 to 0.88 +/- 0.17 to 0.85 +/- 0.15 mm, p = 0.4473).
      CONCLUSION: Eight months of liraglutide use in patients with T2DM and NAFLD
      significantly reduced carotid IMT, a surrogate marker of atherosclerosis,
      independently of glucometabolic changes.

PMID- 26195188
TI  - Prolonged Living as a Refugee from the Area Around a Stricken Nuclear Power Plant
      Increases the Risk of Death.
AB  - Although it is well known that the Great East Japan Earthquake (March 11, 2011)
      resulted in a large number of disaster-related deaths, it is not common knowledge
      that the number of disaster-related deaths continues to increase, even four years
      after the earthquake, in Fukushima Prefecture, where the nuclear power plant
      accident occurred. There has been a lack of a minute and critical analysis for
      the causes for this continuous increase. In this report, the causes for the
      increase in disaster-related deaths in Fukushima Prefecture were analyzed by
      aggregating and comparing multiple data released by public organizations (the
      Reconstruction Agency, the National Police Agency, and Fukushima Prefecture),
      which may also have implications for developing response strategies to other
      disasters. The disaster-related death rate, the dead or missing rate, and the
      refugee rate (the number of disaster-related deaths, dead or missing persons, and
      refugees per 1,000 people) in each prefecture in stricken areas, and also each
      city, county, town, and village in Fukushima Prefecture, were calculated and
      compared with each other. The populations which were used for the calculation of
      each death rate in the area were based on the number of dead victims who had
      lived in the area when the earthquake occurred, regardless of where they were at
      the time of their death. The disaster-related death rate was higher than the dead
      or missing rate in the area around a stricken nuclear power plant in Fukushima
      Prefecture. These areas coincide exactly with the Areas under Evacuation Orders
      because of unsafe radiation levels. The external and internal radiation doses of
      most of the victims of the Great East Japan Earthquake have appeared not to be so
      high to harm their health, until now. The psychological stress associated with
      being displaced from one's home for a long time with an uncertain future may be
      the cause for these disaster-related deaths. There is an urgent need to recognize
      refugees' stressful situations, which could even cause death, and to provide them
      with high-quality medical treatment, including care for their long-term mental
      health

PMID- 26195187
TI  - Early problematic eating behaviours are associated with lower fruit and vegetable
      intake and less dietary variety at 4-5 years of age. A prospective analysis of
      three European birth cohorts.
AB  - Problematic eating behaviours during early childhood could be mediators of poor
      dietary habits. This study aims to prospectively relate early eating behaviours
      with fruit and vegetable (F&V) intake and a healthy diet variety score of
      children aged between 4 and 5 years. Eating behaviours were assessed in three
      European birth cohorts (Generation XXI from Portugal, ALSPAC from the UK and EDEN
      from France) at 4-6, 12-15, 24 and 48-54 months of age, based on the child's
      feeding difficulties, mother's perception of child's poor eating (eating small
      quantities at each meal, not eating enough or needing to be stimulated to eat),
      food refusal and difficulties in the establishment of daily food routines. Daily
      servings of F&V (>1 v. <=1 serving/d, except in Generation XXI: >3 v. <=3) and
      the Healthy Plate Variety Score (categorised by the median score of each sample)
      were calculated using FFQ. Associations were tested by logistic regressions
      adjusted for maternal age, education, smoking during pregnancy, any breast
      feeding and the child's z-score BMI at 4-5 years of age. Children with more
      feeding difficulties, poor eating, food refusal/neophobia and difficulties in
      establishing a daily routine at 12-15, 24 and 48-54 months of age had in general
      lower F&V intake at 4-5 years of age. The association with vegetables was
      slightly stronger than with fruits. These early feeding problems were also
      inversely associated with the variety score at 4-5 years of age, particularly
      when eating behaviours were reported after 12-15 months of age. A better
      understanding of these early feeding difficulties may help define strategies to
      increase the dietary quality in children. 

PMID- 26195189
TI  - The era of antibiotic-resistant bacteria--Time for political, travel medicine and
      healthcare decisions.

PMID- 26195190
TI  - Flying and pregnant?--Regulations of the main airlines in Latin America.

PMID- 26195191
TI  - Characterization of the nuclear import and export signals of pseudorabies virus
      UL31.
AB  - The pseudorabies virus (PRV) UL31 protein (pUL31) is a homologue of the herpes
      simplex virus 1 pUL31, which is a multifunctional protein that is important for
      HSV-1 infection. However, little is known concerning the subcellular localization
      signal of PRV UL31. Here, by transfection with a series of PRV UL31 deletion
      mutants fused to an enhanced yellow fluorescent protein (EYFP) gene, a bipartite
      nuclear localization signal (NLS) and a PY motif NLS of UL31 were identified and
      mapped to amino acids (aa) 4 to 20 (RRRLLRRKSSAARRKTL) and aa 21 to 34
      (TRAARDRYAPYFAY), respectively. Additionally, the predicted nuclear export signal
      (NES) was shown to be nonfunctional. Taken together, this information opens up
      new avenues for investigating the biological functions of UL31 during PRV
      infection. 

PMID- 26195192
TI  - First full-length genome sequence of the polerovirus luffa aphid-borne yellows
      virus (LABYV) reveals the presence of at least two consensus sequences in an
      isolate from Thailand.
AB  - Luffa aphid-borne yellows virus (LABYV) was proposed as the name for a previously
      undescribed polerovirus based on partial genome sequences obtained from samples
      of cucurbit plants collected in Thailand between 2008 and 2013. In this study, we
      determined the first full-length genome sequence of LABYV. Based on phylogenetic
      analysis and genome properties, it is clear that this virus represents a distinct
      species in the genus Polerovirus. Analysis of sequences from sample TH24, which
      was collected in 2010 from a luffa plant in Thailand, reveals the presence of two
      different full-length genome consensus sequences. 

PMID- 26195193
TI  - De novo KCNMA1 mutations in children with early-onset paroxysmal dyskinesia and
      developmental delay.

PMID- 26195194
TI  - Aboveground and Belowground Herbivores Synergistically Induce Volatile Organic
      Sulfur Compound Emissions from Shoots but Not from Roots.
AB  - Studies on aboveground (AG) plant organs have shown that volatile organic
      compound (VOC) emissions differ between simultaneous attack by herbivores and
      single herbivore attack. There is growing evidence that interactive effects of
      simultaneous herbivory also occur across the root-shoot interface. In our study,
      Brassica rapa roots were infested with root fly larvae (Delia radicum) and the
      shoots infested with Pieris brassicae, either singly or simultaneously, to study
      these root-shoot interactions. As an analytical platform, we used Proton Transfer
      Reaction Mass Spectrometry (PTR-MS) to investigate VOCs over a 3 day time period.
      Our set-up allowed us to monitor root and shoot emissions concurrently on the
      same plant. Focus was placed on the sulfur-containing compounds; methanethiol,
      dimethylsulfide (DMS), and dimethyldisulfide (DMDS), because these compounds
      previously have been shown to be biologically active in the interactions of
      Brassica plants, herbivores, parasitoids, and predators, yet have received
      relatively little attention. The shoots of plants simultaneously infested with AG
      and belowground (BG) herbivores emitted higher levels of sulfur-containing
      compounds than plants with a single herbivore species present. In contrast, the
      emission of sulfur VOCs from the plant roots increased as a consequence of root
      herbivory, independent of the presence of an AG herbivore. The onset of root
      emissions was more rapid after damage than the onset of shoot emissions. The
      shoots of double infested plants also emitted higher levels of methanol. Thus,
      interactive effects of root and shoot herbivores exhibit more strongly in the VOC
      emissions from the shoots than from the roots, implying the involvement of
      specific signaling interactions.

PMID- 26195195
TI  - Mycosis Fungoides of the Rectum: Case Report and Review of the Literature.

PMID- 26195196
TI  - Biomacromolecular logic gate, encoder/decoder and keypad lock based on DNA damage
      with electrochemiluminescence and electrochemical signals as outputs.
AB  - Based on the damage of natural DNA, a 3-input/4-output logic gate system and
      other biomacromolecular devices, such as a 2-to-1 encoder, a 1-to-2 decoder and a
      keypad lock, were developed using simultaneously obtained
      electrochemiluminescence (ECL) and cyclic voltammetry (CV) signals as outputs in
      the presence of Ru(bpy)3(2+). 

PMID- 26195198
TI  - Surmounting intrinsic quantum-measurement uncertainties in Gaussian-state
      tomography with quadrature squeezing.
AB  - We reveal that quadrature squeezing can result in significantly better quantum
      estimation performance with quantum heterodyne detection (of H. P. Yuen and J. H.
      Shapiro) as compared to quantum homodyne detection for Gaussian states, which
      touches an important aspect in the foundational understanding of these two
      schemes. Taking single-mode Gaussian states as examples, we show analytically
      that the competition between the errors incurred during tomogram processing in
      homodyne detection and the Arthurs-Kelly uncertainties arising from simultaneous
      incompatible quadrature measurements in heterodyne detection can often lead to
      the latter giving more accurate estimates. This observation is also partly a
      manifestation of a fundamental relationship between the respective data
      uncertainties for the two schemes. In this sense, quadrature squeezing can be
      used to overcome intrinsic quantum-measurement uncertainties in heterodyne
      detection. 

PMID- 26195197
TI  - Effects of oral temazepam on sleep spindles during non-rapid eye movement sleep:
      A high-density EEG investigation.
AB  - Benzodiazepines are commonly used medications that alter sleep spindles during
      non-rapid eye movement (NREM) sleep, however the topographic changes to these
      functionally significant waveforms have yet to be fully elucidated. This study
      utilized high-density electroencephalography (hdEEG) to investigate topographic
      changes in sleep spindles and spindle-range activity caused by temazepam during
      NREM sleep in 18 healthy adults. After an accommodation night, sleep for all
      participants was recorded on two separate nights after taking either placebo or
      oral temazepam 15 mg. Sleep was monitored using 256-channel hdEEG. Spectral
      analysis and spindle waveform detection of sleep EEG data were performed for each
      participant night. Global and topographic data were subsequently compared between
      temazepam and placebo conditions. Temazepam was associated with significant
      increases in spectral power from 10.33 to 13.83 Hz. Within this frequency band,
      temazepam broadly increased sleep spindle duration, and topographically increased
      spindle amplitude and density in frontal and central-posterior regions,
      respectively. Higher frequency sleep spindles demonstrated increased spindle
      amplitude and a paradoxical decrease in spindle density in frontal and
      centroparietal regions. Further analysis demonstrated temazepam both slowed the
      average frequency of spindle waveforms and increased the relative proportion of
      spindles at peak frequencies in frontal and centroparietal regions. These
      findings suggest that benzodiazepines have diverse effects on sleep spindles that
      vary by frequency and cortical topography. Further research that explores the
      relationships between topographic and frequency-dependent changes in
      pharmacologically-induced sleep spindles and the functional effects of these
      waveforms is indicated.

PMID- 26195199
TI  - Thyroid cancer patient perceptions of radioactive iodine treatment choice: Follow
      up from a decision-aid randomized trial.
AB  - BACKGROUND: Patient decision aids (P-DAs) inform medical decision making, but
      longer term effects are unknown. This article describes extended follow-up from a
      thyroid cancer treatment P-DA trial. METHODS: In this single-center, parallel
      design randomized controlled trial conducted at a Canadian tertiary/quaternary
      care center, early-stage thyroid cancer patients from a P-DA trial were contacted
      15 to 23 months after randomization/radioactive iodine (RAI) decision making to
      evaluate longer term outcomes. It was previously reported that the use of the
      computerized P-DA in thyroid cancer patients considering postsurgical RAI
      treatment significantly improved medical knowledge in comparison with usual care
      alone. The P-DA and control groups were compared for the following outcomes:
      feeling informed about the RAI treatment choice, decision satisfaction, decision
      regret, cancer-related worry, and physician trust. In a subgroup of 20
      participants, in-depth interviews were conducted for a qualitative analysis.
      RESULTS: Ninety-five percent (70 of 74) of the original population enrolled in
      follow-up at a mean of 17.1 months after randomization. P-DA users perceived
      themselves to be significantly more 1) informed about the treatment choice (P =
      .008), 2) aware of options (P = .009), 3) knowledgeable about treatment benefits
      (P = .020), and 4) knowledgeable about treatment risks/side effects (P = .001) in
      comparison with controls. There were no significant group differences in decision
      satisfaction (P = .142), decision regret (P = .199), cancer-related worry (P =
      .645), mood (P = .211), or physician trust (P = .764). In the qualitative
      analysis, the P-DA was perceived to have increased patient knowledge and
      confidence in decision making. CONCLUSIONS: The P-DA improved cancer survivors'
      actual and long-term perceived medical knowledge with no adverse effects. More
      research on the long-term outcomes of P-DA use is needed.

PMID- 26195200
TI  - New Methods of Testing and Brain Imaging in Hepatic Encephalopathy: A Review.
AB  - The diagnosis of hepatic encephalopathy is predominantly clinical, and the tests
      available assist in the diagnosis only by excluding other causes. Covert hepatic
      encephalopathy, which is defined as abnormal performance on psychometric tests
      when standard neurologic examination is completely normal, has gained widespread
      attention in recent years due to its effect on quality of life. This review
      focuses on the tests available to aid in the diagnosis of this significant
      complication of liver disease, and discusses the complex pathophysiologic
      mechanisms identified through new imaging techniques and their significance
      toward development of new therapeutic targets for this condition. 

PMID- 26195201
TI  - Clinical and Neurologic Manifestation of Minimal Hepatic Encephalopathy and Overt
      Hepatic Encephalopathy.
AB  - Hepatic encephalopathy (HE) shows a wide spectrum of neuropsychiatric
      manifestations. A combined effort with neuropsychological and psychometric
      evaluation has to be performed to recognize the syndrome, whereas minimal HE
      (MHE) is largely under-recognized. Subtle symptoms of MHE can only be diagnosed
      through specialized neuropsychiatric testing. Early diagnosis and treatment may
      drastically improve the quality of life for many cirrhotic patients. Further
      research to gain better insight into the pathophysiology and diagnostic accuracy
      of HE will help determine future management strategies. 

PMID- 26195202
TI  - Covert Hepatic Encephalopathy: Who Should Be Tested and Treated?
AB  - Covert hepatic encephalopathy is a common problem in cirrhosis, affecting up to
      80% of patients. It is defined as test-dependent brain dysfunction with clinical
      consequences in the setting of cirrhosis in patients who are not disoriented.
      Because it is not apparent clinically, and diagnostic testing has not been
      standardized, the issue has often been ignored in clinical practice. Yet, the
      clinical consequences are notable, including impaired quality of life, diminished
      work productivity, and poor driving skills. 

PMID- 26195203
TI  - Should We Treat Minimal/Covert Hepatic Encephalopathy, and with What?
AB  - Hepatic encephalopathy exists along a continuum from abnormal neuropsychiatric
      testing in the absence of clinical findings to varying degrees of detectable
      clinical findings. The International Society for Hepatic Encephalopathy and
      Nitrogen Metabolism has endorsed the term "covert" to encompass minimal hepatic
      encephalopathy and grade I overt hepatic encephalopathy. Covert hepatic
      encephalopathy has been associated with poor quality of life, decreased
      employment, increased falls, and increased traffic accidents that significantly
      impact quality of life and health care expenditures. Probiotics, nonabsorbable
      dissacharides, rifaximin, and l-ornithine-l-aspartate have been evaluated with
      varying levels of success. Because of the lack of universally accepted diagnostic
      tools, optimal timing of testing and treatment remains controversial. 

PMID- 26195204
TI  - Diets in Encephalopathy.
AB  - As many as 80% of patients with end-stage liver disease and hepatic
      encephalopathy have significant protein-calorie malnutrition. Because of the
      severe hypercatabolic state of cirrhosis, the provision of liberal amounts of
      carbohydrate (at least 35 to 40 kcal/kg per day), and between 1.2 and 1.6 g/kg of
      protein is necessary. Protein restriction is not recommended. Branched-chain
      amino acid supplementation and vegetable protein are associated with improved
      outcomes. Dietary supplementation with vitamins, minerals (with the notable
      exception of zinc) and probiotics should be decided on a case-by-case basis. 

PMID- 26195205
TI  - The Role of Sarcopenia and Frailty in Hepatic Encephalopathy Management.
AB  - Normal regulation of total body and circulating ammonia requires a delicate
      interplay in ammonia formation and breakdown between several organ systems. In
      the setting of cirrhosis and portal hypertension, the decreased hepatic clearance
      of ammonia leads to significant dependence on skeletal muscle for ammonia
      detoxification; however, cirrhosis is also associated with muscle depletion and
      decreased functional muscle mass. Thus, patients with diminished muscle mass and
      sarcopenia may have a decreased ability to compensate for hepatic insufficiency
      and a higher likelihood of developing physiologically significant hyperammonemia
      and hepatic encephalopathy. 

PMID- 26195206
TI  - Ammonia and Its Role in the Pathogenesis of Hepatic Encephalopathy.
AB  - Hepatic encephalopathy (HE) is a commonly encountered sequela of chronic liver
      disease and cirrhosis with significant associated morbidity and mortality.
      Although ammonia is implicated in the pathogenesis of HE, the exact underlying
      mechanisms still remain poorly understood. Its role in the urea cycle, astrocyte
      swelling, and glutamine and gamma-amino-n-butyric acid systems suggests that the
      pathogenesis is multifaceted. Greater understanding in its underlying mechanism
      may offer more targeted therapeutic options in the future, and thus further
      research is necessary to fully understand the pathogenesis of HE. 

PMID- 26195207
TI  - Novel Ammonia-Lowering Agents for Hepatic Encephalopathy.
AB  - Hepatic encephalopathy (HE) is a common complication of cirrhosis, leading to
      frequent hospitalizations. Because ammonia is thought to play an important role
      in the pathogenesis of HE, therapies specifically aimed at reducing ammonia
      levels have been developed for conditions causing hyperammonemia, including HE.
      Ammonia scavengers have been used in HE patients, leading to improvements in
      symptoms. Bowel cleansing with polyethylene glycol has also been studied
      recently, resulting in more rapid improvement in acute HE compared with
      lactulose. Extracorporeal devices have been used in cases of refractory HE but
      currently are used primarily in research settings and not approved for clinical
      management for HE. 

PMID- 26195208
TI  - Treatment of Overt Hepatic Encephalopathy.
AB  - Hepatic encephalopathy (HE) is defined by an altered mental status in the setting
      of portosystemic shunting, with or without cirrhosis. The basis of HE is probably
      multi-factorial, but increased ammonia delivery to the brain is thought to play a
      pivotal role. Medical therapies have typically focused on reducing blood ammonia
      concentrations. These measures are moderately effective, but further improvements
      will require identification of new therapeutic targets. Two medications,
      lactulose and rifaximin, are currently approved for the treatment of HE in the
      USA - new compounds are available off-label, and are in clinical trials. The
      presence of HE is associated with a higher risk of death in cirrhotic patients.
      Liver transplantation typically cures HE, but HE does not increase the MELD
      score, and therefore does not contribute to the likelihood of liver
      transplantation. 

PMID- 26195209
TI  - Diagnosis and Management of Hepatic Encephalopathy in Fulminant Hepatic Failure.
AB  - Hepatic encephalopathy (HE) is associated with cerebral edema (CE), increased
      intracranial pressure (ICP), and subsequent neurologic complications; it is the
      most important cause of morbidity and mortality in fulminant hepatic failure. The
      goal of therapy should be early diagnosis and treatment of HE with measures to
      reduce CE. A combination of clinical examination and diagnostic modalities can
      aid in prompt diagnosis. ICP monitoring and transcranial Doppler help diagnose
      and monitor response to treatment. Transfer to a transplant center and intensive
      care unit admission with airway management and reduction of CE with hypertonic
      saline, mannitol, hypothermia, and sedation are recommended as a bridge to liver
      transplantation. 

PMID- 26195210
TI  - Legal Responsibilities of Physicians When They Diagnose Hepatic Encephalopathy.
AB  - Both covert hepatic encephalopathy (CHE) and overt hepatic encephalopathy (OHE)
      impair the ability to operate machinery. The legal responsibilities of US
      physicians who diagnose and treat patients with hepatic encephalopathy vary among
      states. It is imperative that physicians know the laws regarding reporting in
      their state. OHE represents a neuropsychiatric impairment that meets general
      reporting criteria. The medical advisory boards of the states have not identified
      OHE as a reportable condition. In the absence of validated diagnostic guidelines,
      physicians are not obligated to perform tests for CHE. There is a need for
      explicit guidance from professional associations regarding this issue. 

PMID- 26195211
TI  - HE or not HE? That is Frequently the Question.

PMID- 26195212
TI  - Margaret McCartney: Hunt's plan will shame patients who need costly drugs.

PMID- 26195213
TI  - Environmental and socio-economic determinants of infant mortality in Poland: an
      ecological study.
AB  - BACKGROUND: Health status of infants is related to the general state of health of
      women of child-bearing age; however, women's occupational environment and socio
      economic conditions also seem to play an important role. The aim of the present
      ecological study was to assess the relationship between occupational environment,
      industrial pollution, socio-economic status and infant mortality in Poland.
      METHODS: Data on infant mortality and environmental and socio-economic
      characteristics for the 66 sub-regions of Poland for the years 2005-2011 were
      used in the analysis. Factor analysis was used to extract the most important
      factors explaining total variance among the 23 studied exposures. Generalized
      Estimating Equations model was used to evaluate the link between infant mortality
      and the studied extracted factors. RESULTS: Marked variation for infant mortality
      and the characteristics of industrialization was observed among the 66 sub
      regions of Poland. Four extracted factors: "poor working environment",
      "urbanization and employment in the service sector", "industrial pollution",
      "economic wealth" accounted for 77.3% of cumulative variance between the studied
      exposures. In the multivariate regression analysis, an increase in factor "poor
      working environment" of 1 SD was related to an increase in infant mortality of 40
      (95% CI: 28-53) per 100,000 live births. Additionally, an increase in factor
      "industrial pollution" of 1 SD was associated with an increase in infant
      mortality of 16 (95% CI: 2-30) per 100,000 live births. The factors "urbanization
      and employment in the service sector" and "economic wealth" were not
      significantly related to infant mortality. CONCLUSION: The study findings
      suggested that, at the population level, infant mortality was associated with an
      industrial environment. Strategies to improve working conditions and reduce
      industrial pollution might contribute to a reduction in infant mortality in
      Poland.

PMID- 26195214
TI  - Phylogenetic relationship of Eurasian lynx (Lynx lynx) revealed by complete
      mitochondrial genome.
AB  - The Eurasian lynx (Lynx lynx) is an Endangered species in northeast China. We
      first obtained muscle sample, extracted the sample DNA and sequenced the whole
      mtDNA genome of lynx from northeast China. We reconstructed the phylogenetic tree
      of Eurasian lynx and 10 other most closely related Felidae species. This lynx's
      complete mitogenome is 17 054bp in length, includes 13 protein-coding genes, 22
      tRNA genes, 2 rRNA genes and one control region. The phylogenetic tree confirmed
      previous research results.

PMID- 26195215
TI  - The complete mitochondrial genome of Babax lanceolatus (Passeriformes:
      Timaliidae).
AB  - The complete mitochondrial of Babax lanceolatus is 17 849 bp in length. The
      contents of A, C, T, and G in the mitochondrial genome were 29.53%, 32.62%,
      23.72%, and 14.13%, respectively. The mitogenome of B. lanceolatus were composed
      of 13 typical protein-coding genes, 22 transfer RNA (tRNA) genes, two ribosomal
      RNA (rRNA) genes, and two putative control regions. All protein-coding, rRNA, and
      tRNA genes were similar to those of other Passeriformes in gene arrangement and
      composition. Garrulax perspicillatus was the nearest sister to B. lanceolatus,
      and they were clustered with other species of Garrulax family. The results could
      provide essential information for molecular phylogenetic and evolutionary
      analyses of Passeriformes.

PMID- 26195216
TI  - The complete mitochondrial genome of the White-throated Tinamou, Tinamus guttatus
      (Tinamiformes, Tinamidae).
AB  - The White-throated Tinamou, Tinamus guttatus (Tinamiformes, Tinamidae) is a
      species of the family Tinamidae. Herein, we firstly reported the complete
      mitochondrial genome of White-throated Tinamou. The length of mitogenome was 16
      750 bp, and composed of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and
      1 putative misc-feature region. Most protein-coding genes started with a
      traditional ATG codon, but specially, COX1 and COX2 initiated with an infrequent
      start codon GTG instead, ND3 and ND5 initiated with ATA instead. Protein-coding
      genes terminated with the mitochondria stop codon (TAA/TAG/AGG/AGA) or a single
      base(A/T). The mitogenome structural organization was identical to the closely
      related species Tinamus major. The GC content was 42.66%. To verify the accuracy
      and utility of new determined mitogenome sequences, we constructed the species
      phylogenetic tree with the 12 protein-coding genes of Tinamus guttatus together
      with nine other closely species. We expected that using the full mitogenome to
      address taxonomic issues and study the related evolution events.

PMID- 26195217
TI  - Complete mitochondrial genome of Lycodon flavozonatum and implications for
      Colubridae taxonomy.
AB  - Lycodon flavozonatum, a species of Colubcridae family, is mainly inhabited in
      hilly region of forest in South China, India, Myanmar, and Vietnam. In this
      study, the complete mtDNA of L. flavozonatum is 17 172 bp long, which contains 13
      protein-coding genes, 22 tRNA genes, two rRNA (12S and 16S rRNA), and two control
      regions and a stem-loop region. Most of these genes are encoded in the H-strand;
      only ND6, stem-loop and other nine tRNA genes are on the L-strand. The
      phylogenetic tree among the 14 Serpentiformes species was divided into three
      major clade; Lycodon makes up the first clade, which showed a sister relationship
      to the second clade, Elaphe; Hypsiglena forms the third clade and is sister to
      Lycodon and Elaphe. And the species of L. flavozonatum which we studied belongs
      to the first clade.

PMID- 26195218
TI  - First isolation, identification, phenotypic and genotypic characterization of
      Brucella abortus biovar 3 from dairy cattle in Tanzania.
AB  - BACKGROUND: Brucellosis is a disease of worldwide public health and economic
      importance. Successful control is based on knowledge of epidemiology and strains
      present in an area. In developing countries, most investigations are based on
      serological assays. This study aimed at investigating a dairy herd experiencing
      abortions in order to establish within-herd seroprevalence to Brucella spp.,
      identify, characterize Brucella strains by Multiple Loci Variable Number of
      Tandem Repeats Analysis (MLVA-VNTR) and investigate possible spillover to other
      species. RESULTS: The within-herd seroprevalence in cattle (n = 200) was 48 % (95
      % CI 41-55), using an indirect ELISA, while the Rose Bengal Test (RBT) yielded
      lower prevalence (21.5 %; 95 % CI 16-27). Two sheep (n = 35) and one goat (n =
      50) were seropositive using ELISA while none of the dogs (n = 6) was positive
      with the RBT. Three Brucella were isolated from an aborted fetus and associated
      membranes. Real time PCR (IS711), Bruce-ladder and classical biotyping classified
      the isolates as B. abortus biovar 3. MLVA-VNTR revealed two different but closely
      related genotypes. The isolates showed unique profiles, providing the first
      genotypic data from Tanzania. These genotypes were not related to B. abortus
      biovar 3 reference strain Tulya originally isolated from a human patient in
      Uganda in 1958, unlike the genotypes isolated and characterized recently in
      Kenya. High within-herd prevalence, isolation of the pathogen and abortion
      confirm that B. abortus is circulating in this herd with cattle as reservoir
      hosts. A low seroprevalence in sheep and goats suggests a spillover of B. abortus
      from cattle to small ruminants in the herd. CONCLUSIONS: This is the first
      isolation and characterization of B. abortus biovar 3 from a dairy cow with
      abortion in Tanzania. The origin of the Tanzanian genotypes remain elusive,
      although they seem to be related to genotypes found in Europe, Turkey and China
      but not related to B. abortus biovar 3 reference strain or genotypes from Kenya.
      Importantly, replacement heifers are commonly sourced from large farms like this
      to smallholder farmers, which poses risk of spread of bacteria to other herds. B.
      abortus is a significant zoonotic risk and animal health problem in this
      production system, therefore further studies on humans is recommended.

PMID- 26195219
TI  - IRF2BP2 Reduces Macrophage Inflammation and Susceptibility to Atherosclerosis.
AB  - RATIONALE: Inflammation impairs macrophage cholesterol clearance from vascular
      tissues and promotes atherosclerosis. Inflammatory macrophages suppress
      expression of the transcription cofactor interferon regulatory factor 2-binding
      protein 2 (IRF2BP2), and genetic variants near IRF2BP2 associate with ischemic
      heart disease progression in humans. OBJECTIVES: To test whether IRF2BP2 in
      macrophages affects atherosclerosis in mice and humans. METHODS AND RESULTS: We
      generated mice that delete IRF2BP2 in macrophages. IRF2BP2-deficient macrophages
      worsened atherosclerosis in irradiated low-density lipoprotein receptor null
      recipient mice and in apolipoprotein E null mice. IRF2BP2-deficient macrophages
      were inflammatory and had impaired cholesterol efflux because of their inability
      to activate the cholesterol transporter ABCA1 in response to cholesterol loading.
      Their expression of the anti-inflammatory transcription factor Kruppel-like
      factor 2 was markedly reduced. Promoter studies revealed that IRF2BP2 is required
      for MEF2-dependent activation of Kruppel-like factor 2. Importantly, restoring
      Kruppel-like factor 2 in IRF2BP2-deficient macrophages attenuated M1 inflammatory
      and rescued M2 anti-inflammatory gene activation and improved the cholesterol
      efflux deficit by restoring ABCA1 activation in response to cholesterol loading.
      In a cohort of 1066 angiographic cases and 1011 controls, homozygous carriers of
      a deletion polymorphism (rs3045215) in the 3' untranslated region sequence of
      human IRF2BP2 mRNA had a higher risk of coronary artery disease (recessive model,
      odds ratio [95% confidence interval]=1.560 [1.179-2.065], P=1.73E-03) and had
      lower IRF2BP2 (and Kruppel-like factor 2) protein levels in peripheral blood
      mononuclear cells. The effect of this deletion polymorphism to suppress protein
      expression was confirmed in luciferase reporter studies. CONCLUSION: Ablation of
      IRF2BP2 in macrophages worsens atherosclerosis in mice, and a deletion variant
      that lowers IRF2BP2 expression predisposes to coronary artery disease in humans.

PMID- 26195220
TI  - Endothelial NO-Synthase Gene-Enhanced Progenitor Cell Therapy for Pulmonary
      Arterial Hypertension: The PHACeT Trial.
AB  - RATIONALE: Pulmonary arterial hypertension (PAH) remains a progressive and
      eventually lethal disease characterized by increased pulmonary vascular
      resistance because of loss of functional lung microvasculature, primarily at the
      distal (intracinar) arteriolar level. Cell-based therapies offer the potential to
      repair and regenerate the lung microcirculation and have shown promise in
      preclinical evaluation in experimental models of PAH. OBJECTIVE: The Pulmonary
      Hypertension and Angiogenic Cell Therapy (PHACeT) trial was a phase 1, dose
      escalating clinical study of the tolerability of culture-derived endothelial
      progenitor cells, transiently transfected with endothelial nitric oxide synthase,
      in patients with PAH refractory to PAH-specific therapies. METHODS AND RESULTS:
      Seven to 50 million endothelial nitric oxide synthase-transfected endothelial
      progenitor cells, divided into 3 doses on consecutive days, were delivered into
      the right atrium via a multiport pulmonary artery catheter during continuous
      hemodynamic monitoring in an intensive care unit setting. Seven patients (5
      women) received treatment from December 2006 to March 2010. Cell infusion was
      well tolerated, with no evidence of short-term hemodynamic deterioration; rather,
      there was a trend toward improvement in total pulmonary resistance during the 3
      day delivery period. However, there was 1 serious adverse event (death) which
      occurred immediately after discharge in a patient with severe, end stage disease.
      Although there were no sustained hemodynamic improvements at 3 months, 6-minute
      walk distance was significantly increased at 1, 3, and 6 months. CONCLUSION:
      Delivery of endothelial progenitor cells overexpressing endothelial nitric oxide
      synthase was tolerated hemodynamically in patients with PAH. Furthermore, there
      was evidence of short-term hemodynamic improvement, associated with long-term
      benefits in functional and quality of life assessments. However, future studies
      are needed to further establish the efficacy of this therapy. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00469027.

PMID- 26195221
TI  - Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac
      Adaptation in Chronic Heart Failure.
AB  - RATIONALE: In chronic heart failure, increased adrenergic activation contributes
      to structural remodeling and altered gene expression. Although adrenergic
      signaling alters histone modifications, it is unknown, whether it also affects
      other epigenetic processes, including DNA methylation and its recognition.
      OBJECTIVE: The aim of this study was to identify the mechanism of regulation of
      the methyl-CpG-binding protein 2 (MeCP2) and its functional significance during
      cardiac pressure overload and unloading. METHODS AND RESULTS: MeCP2 was
      identified as a reversibly repressed gene in mouse hearts after transverse aortic
      constriction and was normalized after removal of the constriction. Similarly,
      MeCP2 repression in human failing hearts resolved after unloading by a left
      ventricular assist device. The cluster miR-212/132 was upregulated after
      transverse aortic constriction or on activation of alpha1- and beta1
      adrenoceptors and miR-212/132 led to repression of MeCP2. Prevention of MeCP2
      repression by a cardiomyocyte-specific, doxycycline-regulatable transgenic mouse
      model aggravated cardiac hypertrophy, fibrosis, and contractile dysfunction after
      transverse aortic constriction. Ablation of MeCP2 in cardiomyocytes facilitated
      recovery of failing hearts after reversible transverse aortic constriction.
      Genome-wide expression analysis, chromatin immunoprecipitation experiments, and
      DNA methylation analysis identified mitochondrial genes and their transcriptional
      regulators as MeCP2 target genes. Coincident with its repression, MeCP2 was
      removed from its target genes, whereas DNA methylation of MeCP2 target genes
      remained stable during pressure overload. CONCLUSIONS: These data connect
      adrenergic activation with a microRNA-MeCP2 epigenetic pathway that is important
      for cardiac adaptation during the development and recovery from heart failure.

PMID- 26195223
TI  - Underlying mechanism of drug-drug interaction between pioglitazone and
      gemfibrozil: Gemfibrozil acyl-glucuronide is a mechanism-based inhibitor of
      CYP2C8.
AB  - While co-administered gemfibrozil can increase the area under the
      concentration/time curve (AUC) of pioglitazone more than 3-fold, the underlying
      mechanism of the drug-drug interaction between gemfibrozil and pioglitazone has
      not been fully understood. In the present study, gemfibrozil preincubation time
      dependently inhibited the metabolism of pioglitazone in the cytochrome P450 (CYP)
      and UDP-glucuronosyltransferase (UGT)-activated human liver microsomes. We
      estimated the kinact and K'app values, which are the maximum inactivation rate
      constant and the apparent dissociation constant, of gemfibrozil to be 0.071 min(
      1) and 57.3 MUM, respectively. In this study, the kobs, in vivo value was defined
      as a parameter that indicates the potency of the mechanism-based inhibitory
      effect at the blood drug concentration in vivo. The kobs, in vivo values of
      potent mechanism-based inhibitors, clarithromycin and erythromycin, were
      estimated to be 0.0096 min(-1) and 0.0051 min(-1), respectively. The kobs, in
      vivo value of gemfibrozil was 0.0060 min(-1), which was comparable to those of
      clarithromycin and erythromycin, suggesting that gemfibrozil could be a mechanism
      based inhibitor as potent as clarithromycin and erythromycin in vivo. 

PMID- 26195222
TI  - Tetanus toxoid-loaded layer-by-layer nanoassemblies for efficient systemic,
      mucosal, and cellular immunostimulatory response following oral administration.
AB  - The present study reports the tetanus toxoid (TT)-loaded layer-by-layer
      nanoassemblies (layersomes) with enhanced protection, permeation, and
      presentation for comprehensive oral immunization. The stable and lyophilized TT
      loaded layersomes were prepared by a thin-film hydration method followed by
      alternate layer-by-layer coating of an electrolyte. The developed system was
      assessed for in vitro stability of antigen and formulation, cellular uptake, ex
      vivo intestinal uptake, and immunostimulatory response using a suitable
      experimental protocol. Layersomes improved the stability in simulated biological
      media as well as protected the integrity/conformation and native 3D structure of
      TT as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), circular dichroism (CD), and fluorescence spectroscopy, respectively. The
      cell culture studies demonstrated a 3.8-fold higher permeation of layersomes in
      Caco-2 cells and an 8.5-fold higher uptake by antigen-presenting cells (RAW
      264.7). The TT-loaded layersomes elicited a complete immunostimulatory profile
      consisting of higher systemic (serum IgG titer), mucosal (sIgA titer), and
      cellular (interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) levels) immune
      response after peroral administration in mice. The modified TT inhibition assay
      further confirmed the elicitation of complete protective levels of anti-TT
      antibody (>0.1 IU/mL) by layersomes. In conclusion, the proposed strategy is
      expected to contribute significantly in the field of stable liposome technology
      for mass immunization through the oral route.

PMID- 26195224
TI  - Variation in the inhibitory potency of terbinafine among genetic variants of
      CYP2D6.
AB  - Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic enzyme that is involved in
      the metabolism of many drugs. Terbinafine (TER) is a CYP2D6 inhibitor and causes
      persistent drug interactions in the clinical setting; however, its inhibitory
      mechanism and the differences in its inhibitory potency among genetic variants of
      CYP2D6 remain to be investigated. This study aimed to investigate the inhibitory
      mechanism of TER and the differences in its inhibitory potency among three CYP2D6
      variants, CYP2D6.1, CYP2D6.2, and CYP2D6.10. In a competitive inhibition study,
      the metabolic activity of the CYP2D6 was assessed based on their demethylation of
      dextromethorphan in the presence or absence of TER, and the time-dependency of
      the inhibitory effects were examined by preincubating the enzymes with TER. TER
      had weaker inhibitory effects on CYP2D6.2 and CYP2D6.10 than on CYP2D6.1; i.e.,
      TER exhibited Ki values (the concentration of inhibitor that results in half
      maximal inhibition) of 0.0525, 0.355, and 1.85 MUM for CYP2D6.1, CYP2D6.2, and
      CYP2D6.10, respectively. The inhibitory effects of TER were not time-dependent.
      Since TER's Ki value for CYP2D6.10 was 35.2-fold higher than its Ki value for
      CYP2D6.1, the CYP2D6 genotype of subjects should be taken into account when
      estimating the severity of drug interactions involving TER. 

PMID- 26195225
TI  - Serum flecainide S/R ratio reflects the CYP2D6 genotype and changes in CYP2D6
      activity.
AB  - The aims of this study were to clarify whether the ratio of S- to R-flecainide
      (S/R ratio) in the serum flecainide concentration was associated with the
      stereoselectivity of flecainide metabolism, and to investigate the effects of the
      cytochrome P450 (CYP) 2D6 (CYP2D6) genotype and CYP2D6 inhibitor on the serum
      flecainide S/R ratio. In vitro studies using human liver microsomes and cDNA
      expressed CYP isoforms suggested that variability in the serum flecainide S/R
      ratio was associated with the stereoselectivity of CYP2D6-mediated flecainide
      metabolism. We examined the serum flecainide S/R ratio in 143 patients with
      supraventricular tachyarrhythmia. The S/R ratio was significantly lower in
      intermediate metabolizers and poor metabolizers (IMs/PMs) than in extensive
      metabolizers (EMs) identified by the CYP2D6 genotype. The cut-off value for the
      S/R ratio to allow the discrimination between CYP2D6 EMs and IMs/PMs was 0.99.
      The S/R ratio in patients with co-administration of bepridil, a potent CYP2D6
      inhibitor, was lower than 0.99, regardless of the CYP2D6 genotype status. Other
      factors, including age, sex, body weight, and renal function, did not affect the
      serum flecainide S/R ratio. This study suggests that the serum flecainide S/R
      ratio reflects the CYP2D6 genotype and changes in CYP2D6 activity on co
      administration of a CYP2D6 inhibitor. 

PMID- 26195226
TI  - Behcet Disease Presenting With Cardiac and Pulmonary Masses.
AB  - Computed tomography and magnetic resonance imaging features of inflammatory
      intracardiac and pulmonary masses secondary to Behcet disease have not been well
      described in the literature. We present a case of Behcet disease, presenting with
      enhancing cardiac and pulmonary inflammatory masses that mimicked the imaging
      appearance of metastatic cardiac angiosarcoma. Subsequent magnetic resonance
      imaging examination showed the mass reduced in size with immunosuppressive
      therapy. This case highlights the importance of considering Behcet disease in the
      differential diagnosis for an enhancing cardiac mass. 

PMID- 26195227
TI  - Percutaneous Paravalvular Leak Closure in "Invisible" Mitral Valve Bioprosthesis
      Without Radio-Opaque Indicators.

PMID- 26195228
TI  - Oral Anticoagulation for Stroke Prevention in Canadian Practice: Stroke
      Prevention and Rhythm Interventions in Atrial Fibrillation (SPRINT-AF)
      Registry(.).
AB  - BACKGROUND: We explored patterns of and factors associated with the use of oral
      anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation
      (AF) in contemporary Canadian practice. METHODS: Phase 1 of the Stroke Prevention
      and Rhythm Intervention in Atrial Fibrillation (SPRINT-AF) registry was a cross
      sectional retrospective study of patients with nonvalvular AF (NVAF). From
      December 2012-July 2013, 936 consecutive patients with NVAF were enrolled in
      SPRINT-AF. Of the 782 patients treated with OAC, the proportion treated with
      warfarin and a new oral anticoagulant (NOAC) was 53.2% and 46.8%, respectively.
      The rate of OAC use was 90.9% among patients with a CHADS2 (Congestive Heart
      Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack) score >=
      2. RESULTS: On multivariable analysis, the 2 strongest factors associated with
      NOAC use (compared with warfarin use) were an improved side effect profile (as
      perceived by the patient) and improved efficacy (as perceived by the physician)
      (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.06-0.17; P < 0.01 and OR,
      0.52; 95% CI, 0.36-0.76; P < 0.01, respectively). Lower cost was strongly
      associated with warfarin use (OR, 5.16; 95% CI, 3.49-7.63; P < 0.01).
      CONCLUSIONS: In this contemporary Canadian AF registry, the rate of guideline
      concordant OAC use was high. About half of OAC-treated patients received NOACs.
      Patient- and physician-driven preferences, such as side effect profile, perceived
      greater efficacy, and cost, were strong determinants of NOAC use over warfarin
      use.

PMID- 26195229
TI  - The Risk of Ischemic Heart Disease and Stroke Among Immigrant Populations: A
      Systematic Review.
AB  - BACKGROUND: The increasing frequency of global migration to Canada and other high
      income countries has highlighted the need for information on the risk of ischemic
      heart disease (IHD) and stroke among migrant populations. METHODS: Using the
      MEDLINE and EMBASE databases, we conducted an English-language literature review
      of articles published from 2000 to 2014 to study patterns in the incidence of IHD
      or stroke in migrant populations to high-income countries. Our search revealed 17
      articles of interest. All studies stratified immigrants according to country or
      region of birth, except 2 from Canada and 1 from Denmark, in which all immigrant
      groups were analyzed together. RESULTS: The risk of IHD or stroke varied by
      country of origin, country of destination, and duration of residence. In our
      review we found that most migrant groups to Western Europe were at a similar or
      higher risk of IHD and stroke compared with the host population. Those at a
      higher risk included many Eastern European, Middle-Eastern, and South Asian
      immigrants. When duration of residence was considered, it appeared that in most
      migrants the risk of IHD worsened over time. In contrast, immigrants overall were
      at lower risk of myocardial infarction and stroke in Ontario compared with long
      term residents of Canada. CONCLUSIONS: The risks of IHD and stroke vary widely in
      immigrant populations in Western Europe. Detailed studies of immigrants to Canada
      according to country of birth and duration of residence should be undertaken to
      guide future cardiovascular health promotion initiatives.

PMID- 26195230
TI  - An Enhanced Pre- and Postnatal Development Study in Cynomolgus Monkeys with
      Tabalumab: A Human IgG4 Monoclonal Antibody.
AB  - Tabalumab, a human IgG4 monoclonal antibody (mAb) with neutralizing activity
      against both soluble and membrane B-cell activating factor (BAFF), has been under
      development for the treatment of autoimmune diseases. The purpose of this study
      was to determine the potential adverse effects of maternal tabalumab exposure on
      pregnancy, parturition, and lactation of the mothers and on the growth,
      viability, and development of the offspring through postnatal day (PND) 204.
      Tabalumab was administered by subcutaneous injection to presumed pregnant
      cynomolgus monkeys (16-19 per group) every 2 weeks from gestation day (GD) 20 to
      22 until parturition at doses of 0, 0.3, or 30 mg/kg. Evaluations in mothers and
      infants included clinical signs, body weight, toxicokinetics, blood lymphocyte
      phenotyping, T-cell-dependent antibody response (infants only), antitherapeutic
      antibody (ATA), organ weights (infants only), and gross and microscopic
      histopathology. Infants were also examined for external and visceral morphologic
      and neurobehavioral development. There were no adverse tabalumab-related effects
      on maternal or infant endpoints. An expected pharmacological decrease in
      peripheral blood B-lymphocytes occurred in adults and infants; however, B-cell
      recovery was evident by PND154 in adults and infants at 0.3 mg/kg and by PND204
      in infants at 30 mg/kg. At 30 mg/kg, a reduced IgM antibody response to T-cell
      dependent antigen keyhole limpet hemocyanin (KLH) was observed following primary
      immunization. Following secondary KLH immunization, all infants in both dose
      groups mounted anti-KLH IgM and IgG antibody responses similar to control.
      Placental and mammary transfer of tabalumab was demonstrated. In conclusion, the
      no-observed-adverse-effect level for maternal and developmental toxicity was 30
      mg/kg, the highest dose tested. Exposures at 30 mg/kg provide a margin of safety
      of 16* the anticipated clinical exposure.

PMID- 26195231
TI  - Diastolic myocardial dysfunction by tissue Doppler imaging predicts mortality in
      patients with cerebral infarction.
AB  - Several clinical prediction score models have been investigated for predicting
      mortality in patients with cerebral infarction. However, none of these include
      echocardiographic measures. Our objective was to evaluate the prognostic value of
      tissue Doppler imaging (TDI) of the myocardium in patients with cerebral
      infarction. Two hundred forty-four patients with cerebral infarction and
      subsequent echocardiographic examination in sinus rhythm were identified. Using
      TDI in three apical projections, longitudinal mitral annular velocities were
      obtained in six segments. Cox regression models, C-statistics and
      reclassification analysis were performed for global and segmental e'. During a
      median follow-up of 3 years 42 patients died. Patients who died had significantly
      impaired systolic and diastolic function (determined by LVEF and E/e'). The risk
      of dying increased with decreasing global e', being approximately 13 times higher
      for patients in the lowest tertile compared to patients in the highest tertile
      (HR 13.4 [3.2;56.3], p < 0.001). Patients with significantly impaired global e'
      showed increased mortality after multivariable adjustment for: LVEF, E/e', age,
      gender, heart failure, chronic obstructive pulmonary disease, prior cerebral
      infarction, ischemic heart disease, cancer, hypertension, hypercholesterolemia,
      carotid stenosis, mitral regurgitation, liver disease and thromboembolisms (HR
      1.9 [1.1;3.2]), per 1 cm/s decrease, p < 0.05). Similar pattern was seen in
      segmental analyses of the e'. In contrast to e', no conventional
      echocardiographic parameters remained independent predictors of mortality after
      multivariable adjustment. Diastolic myocardial dysfunction determined as e' by
      TDI is a significant predictor of mortality in patients with cerebral infarction.
      Applying this parameter can aid the prognostic assessment after cerebral
      infarction.

PMID- 26195232
TI  - Self-reported symptoms and healthcare seeking in the general population-
      exploring "The Symptom Iceberg".
AB  - BACKGROUND: Research has illustrated that the decision-making process regarding
      healthcare seeking for symptoms is complex and associated with a variety of
      factors, including gender differences. Enhanced understanding of the frequency of
      symptoms and the healthcare seeking behaviour in the general population may
      increase our knowledge of this complex field. The primary objective of this study
      was to estimate the prevalence of self-reported symptoms and the proportion of
      individuals reporting GP contact, in a large Danish nationwide cohort. A
      secondary objective was to explore gender differences in GP contacts in response
      to experiencing one of the 44 predefined symptoms. METHODS: A Danish nationwide
      cohort study including a random sample of 100,000 individuals, representative of
      the adult Danish population aged 20 years or above. A web-based questionnaire
      survey formed the basis of this study. A total of 44 different symptoms covering
      a wide area of alarm symptoms and non-specific frequently occurring symptoms were
      selected based on extensive literature search. Further, items regarding contact
      to the GP were included. Data on socioeconomic factors were obtained from
      Statistics Denmark. RESULTS: A total of 49,706 subjects completed the
      questionnaire. Prevalence estimates of symptoms varied from 49.4% (24,537)
      reporting tiredness to 0.11% (54) reporting blood in vomit. The mean number of
      reported symptoms was 5.4 (men 4.8; women 6.0). The proportion of contact to the
      GP with at least one symptom was 37%. The largest proportion of GP contacts was
      seen for individuals reporting blood in the urine (73.2%), whereas only 11.4% of
      individuals with increase in waist circumference reported GP contact. For almost
      2/3 of the symptoms reported, no gender differences were found concerning the
      proportion leading to GP contacts. CONCLUSION: Prevalence of symptoms and GP
      contacts are common in this overview of 44 different self-reported symptoms. For
      almost 2/3 of the reported symptoms no gender differences were found concerning
      the proportion leading to GP contacts. An enhanced understanding of healthcare
      seeking decisions may assist healthcare professionals in identifying patients who
      are at risk of postponing contact to the GP and may help development of health
      campaigns targeting these individuals.

PMID- 26195233
TI  - Quality of Life, Family Support, and Comorbidities in Institutionalized Elders
      With and Without Symptoms of Depression.
AB  - The institutionalization of elders can decrease the health status and quality of
      life in this population. The aim of this study was to analyze the socio
      demographic, quality of life, family support, and comorbidities variables in
      institutionalized elders with and without symptoms of depression. This was a
      cross-sectional study in institutions for long permanence for the elderly in the
      State of Rio Grande do Norte, Brazil. Two institutionalized elderly groups were
      compared (138 elders: 69 with and 69 without depressive symptoms). The
      instruments used were: mini-mental state examination, geriatric depression scale
      in the reduced version, socio-demographic questionnaire, quality of life (World
      Health Organization Quality of Life abbreviated-WHOQOL-bref), and inventory of
      perception of family support. Elders with depressive symptoms had inferior
      quality of life than those without depressive symptoms. Other factors that
      negatively influenced the quality of life in this population include: low
      economic conditions, occurrence of comorbidities, and deficient family
      assistance. These results have important implications in the decision making
      process with regard to strategies for improving the health status of
      institutionalized elders.

PMID- 26195234
TI  - Organizational Health in Our Educational System.

PMID- 26195235
TI  - Influence of cafeteria diet and fish oil in pregnancy and lactation on pups' body
      weight and fatty acid profiles in rats.
AB  - PURPOSE: The aim was to determine the effects of cafeteria diet (CD) and fish oil
      supplements given to pregnant and lactating rats on the birth weight and fatty
      acid profiles of their offspring. METHODS: Female rats were given standard diet
      (STD) or CD for 22 days before pregnancy. After mating, some animals remained on
      STD or CD; for some CD rats, the diet was supplemented with 8.78 % fish oil (CD
      FO). After 12 days, half the CD-FO group returned to CD (CD-FO12) and the others
      remained on CD-FO. RESULTS: At birth, body weights of pups of the three CD groups
      were lower than STD, maintained until 21 days in the CD-FO group only. At the end
      of lactation, dams of the CD groups had increased plasma triacylglycerols (TAG),
      non-esterified fatty acids, and glycerol concentrations, whereas most n-6 long
      chain polyunsaturated fatty acids (LCPUFA) were decreased, the effect being
      greatest in the CD-FO group, where most n-3 LCPUFA were increased and indices of
      Delta(5) and Delta(6) desaturase activities decreased. The 21-day-old pups of the
      CD group had increased plasma TAG, not present in the CD-FO group, which had
      increased 3-hydroxybutyrate concentrations. In both 2- and 21-day-old CD pups,
      plasma concentrations of ARA were lower than STD, and even lower in the two CD-FO
      groups. CONCLUSIONS: The effect of CD and CD-FO decreasing pups body weight could
      be related to decreased concentrations of ARA, caused by the inhibition of the
      Delta(5) and Delta(6) desaturases in the pathway of n-6 LCPUFA biosynthesis.

PMID- 26195237
TI  - Reversible cursive agraphia.

PMID- 26195236
TI  - Cardiovascular and respiratory outcome of preconditioned rats submitted to
      chronic intermittent hypoxia.
AB  - NEW FINDINGS: What is the central question of this study? What are the effects of
      hypoxic preconditioning upon the cardiovascular and respiratory responses to
      subsequent episodes of chronic intermittent hypoxia? What is the main finding and
      its importance? The cardiovascular and respiratory responses to a chronic
      intermittent hypoxia protocol were not altered by previous exposure to
      intermittent or sustained hypoxia. These findings show that preconditioning to
      hypoxia produced neither facilitation nor protection from the cardiovascular and
      respiratory dysfunctions in response to subsequent episodes of chronic
      intermittent hypoxia in juvenile rats. Rats exposed to chronic intermittent
      hypoxia (CIH) develop hypertension, which is associated with changes in the
      coupling of sympathetic and respiratory activities. In this study, we
      hypothesized that previous preconditioning to intermittent or sustained hypoxia
      would affect cardiovascular and respiratory changes produced by subsequent
      protocols of CIH. To test this hypothesis, male Wistar rats were preconditioned
      to either 10 days of CIH or 24 h of sustained hypoxia (SH). After the initial
      exposure to hypoxia, rats were maintained in normoxic conditions for 15 days
      before a new protocol of CIH during 10 days. Cardiovascular and respiratory
      variables obtained from groups of preconditioned rats were compared with a group
      of rats exposed to CIH for the first time and also to a group of rats maintained
      in normoxic conditions throughout the period of time of the respective
      preconditioning protocol. The data show that CIH produced a similar increase in
      arterial pressure and heart rate in both CIH and SH preconditioning protocols.
      Respiratory parameters during basal conditions were also not affected by
      preconditioning to either CIH or SH. We conclude that previous exposure to CIH or
      SH preconditioning does not facilitate or prevent the cardiovascular changes
      produced by CIH.

PMID- 26195238
TI  - Susceptibility-weighted imaging in Todd paralysis.

PMID- 26195239
TI  - Midlife personality and risk of Alzheimer disease and distress: A 38-year follow
      up.

PMID- 26195240
TI  - Clinical Reasoning: An unusual diagnostic triad. Susac syndrome, or
      retinocochleocerebral vasculopathy.

PMID- 26195241
TI  - Clinical Reasoning: A 44-year-old woman with rapidly progressive weakness and
      ophthalmoplegia.

PMID- 26195242
TI  - Teaching NeuroImages: Red forehead dot syndrome and migraine revisited.

PMID- 26195243
TI  - The Usefulness of International Cooperation in the Repair of Inguinal Hernias in
      Sub-Saharan Africa.
AB  - INTRODUCTION: The burden of disease and mortality associated with inguinal hernia
      in Africa, especially in sub-Saharan Africa, is very high. The purpose of this
      study is to show that International Cooperation work in the field of hernia
      repair is effective; it minimizes the delay in hernia repairs in the targeted
      population, and can prevent a large number of disability-adjusted life years
      (DALYs). MATERIALS AND METHODS: As a part of an International Cooperation
      program, a total of 990 black patients with inguinal hernias were studied, in
      whom hernioplasty was performed using polypropylene mesh. The type of hernia and
      surgical technique were studied. Indicators of scientific and technical quality,
      indicators of efficiency and of effectiveness were analyzed. The results on the
      usefulness of interventions were calculated as avoided DALYs. RESULTS: Surgery
      was performed on 926 patients with a total of 1033 hernia repairs. 87.2 % of the
      repairs were made with mesh. There was no mortality in the series, complications
      were minor, and 85.7 % of patients remained less than 24 h in the center. There
      was a 2.8 % of recurrence, with a follow-up 58.7 % of the patients in the first
      year. 5014 DALYs were avoided, and the average of the avoided DALYs per patient
      was of 5.41. CONCLUSIONS: Hernia repair with mesh in low development countries is
      a procedure with low morbidity and high effectiveness that can prevent a large
      number of DALYs.

PMID- 26195244
TI  - Multilevel analysis of elastic morphology: The mantis shrimp's spring.
AB  - Spring systems, whether natural or engineered, are composed of compliant and
      rigid regions. Biological springs are often similar to monolithic structures that
      distribute compliance and rigidity across the whole system. For example, to
      confer different amounts of compliance in distinct regions within a single
      structure, biological systems typically vary regional morphology through
      thickening or elongation. Here, we analyze the monolithic spring in mantis shrimp
      (Stomatopoda) raptorial appendages to rapidly acquire or process prey. We
      quantified the shape of cross-sections of the merus segment of the raptorial
      appendage. We also examined specific regions of the merus that are hypothesized
      to either store elastic energy or provide structural support to permit energy
      storage in other regions of the system. We found that while all mantis shrimp
      contain thicker ventral bars in distal cross-sections, differences in thickness
      are more pronounced in high-impact "smasher" mantis shrimp than in the slower
      striking "spearer" mantis shrimp. We also found that spearer cross-sections are
      more circular while those of smashers are more eccentric with elongation along
      the dorso-ventral axis. The results suggest that the regional thickening of
      ventral bars provides structural support for resisting spring compression and
      also reduces flexural stiffness along the system's long axis. This multilevel
      morphological analysis offers a foundation for understanding the evolution and
      mechanics of monolithic systems in biology.

PMID- 26195245
TI  - Assessing incremental value of biomarkers with multi-phase nested case-control
      studies.
AB  - Accurate risk prediction models are needed to identify different risk groups for
      individualized prevention and treatment strategies. In the Nurses' Health Study,
      to examine the effects of several biomarkers and genetic markers on the risk of
      rheumatoid arthritis (RA), a three-phase nested case-control (NCC) design was
      conducted, in which two sequential NCC subcohorts were formed with one nested
      within the other, and one set of new markers measured on each of the subcohorts.
      One objective of the study is to evaluate clinical values of novel biomarkers in
      improving upon existing risk models because of potential cost associated with
      assaying biomarkers. In this paper, we develop robust statistical procedures for
      constructing risk prediction models for RA and estimating the incremental value
      (IncV) of new markers based on three-phase NCC studies. Our method also takes
      into account possible time-varying effects of biomarkers in risk modeling, which
      allows us to more robustly assess the biomarker utility and address the question
      of whether a marker is better suited for short-term or long-term risk prediction.
      The proposed procedures are shown to perform well in finite samples via
      simulation studies. 

PMID- 26195246
TI  - Energetic Materials Based on 5,5'-Diamino-4,4'-dinitramino-3,3'-bi-1,2,4
      triazole.
AB  - A simple and straightforward synthesis of 5,5'-diamino-4,4'-dinitramino-3,3'-bi
      1,2,4-triazole by the selective nitration of 4,4',5,5'-tetraamino-3,3'-bi-1,2,4
      triazole is presented. The interaction of the amino and nitramino groups improves
      the energetic properties of this functionalized bitriazole. For a deeper
      investigation of these properties, various nitrogen-rich derivatives were
      synthesized. The new compounds were investigated and characterized by
      spectroscopy ((1)H and (13)C NMR, IR, Raman), elemental analysis, mass
      spectrometry, differential thermal analysis (DTA), X-ray analysis, and impact and
      friction sensitivities (IS, FS). X-ray analyses were performed and deliver
      insight into structural characteristics with which the stability of the compounds
      can be explained. The standard enthalpies of formation were calculated for all
      compounds at the CBS-4M level of theory, revealing highly positive heats of
      formation. The energetic performance of the new molecules was predicted with the
      EXPLO5 V6.02 computer. A small-scale shock reactivity test (SSRT) and a toxicity
      test gave a first impression of the performance and toxicity of selective
      compounds.

PMID- 26195248
TI  - [Revised certification criteria for regional and national stroke units in
      Germany].
AB  - The revised criteria for regional and national German stroke units (SU) defined
      by the SU commission of the German Stroke Society come into effect on 1 July
      2015. Due to the already high level of quality, various aspects only needed minor
      adjustments and definitions; therefore, the majority of minimum structural
      standards were carried forward. For medical personnel thresholds for when staff
      further recruitment is necessary were defined for the first time. The current
      evidence for endovascular thrombectomy (ET) resulted in enhanced standards for
      acute brain vessel imaging, network formation and timely transport between
      regional and national SUs with and without ET capability. It further confirmed
      certification criteria for national SUs that have been valid since 2012: at least
      two neurointerventionalists as staff members enabling ET on a 24/7 basis.
      Diagnostic of atrial fibrillation (AF) has been newly implemented following
      current evidence and internal audits on an annual basis have now become
      obligatory. Overall, activities to ensure and improve quality must not only be
      restricted to the minimally required criteria of SU certification but should also
      incorporate recommendations of the SU commission. The continuous further
      development of German SU in recent years underlines the importance of the
      certification procedure as a guarantee of a minimum standard and as the driving
      force of sustainable quality improvements. 

PMID- 26195247
TI  - Implementation of a Multicomponent intervention to Prevent Physical Restraints In
      Nursing home residenTs (IMPRINT): study protocol for a cluster-randomised
      controlled trial.
AB  - BACKGROUND: Physical restraints such as bedrails and belts are regularly applied
      in German nursing homes despite clear evidence showing their lack of
      effectiveness and safety. In a cluster-randomised controlled trial, the efficacy
      and safety of a guideline-based multicomponent intervention programme has been
      proven. The present study aims to evaluate the effectiveness of two different
      versions of the original intervention in nursing home residents in four different
      regions throughout Germany. METHODS/DESIGN: The study is a pragmatic cluster
      randomised controlled trial comparing two intervention groups, i.e. (1) the
      updated original multicomponent intervention programme and (2) the concise
      version of the updated programme, with a control group receiving optimised usual
      care. The first intervention group receives an educational programme for all
      nurses, additional training and structured support for nominated key nurses,
      printed study material and other supportive material. In the second intervention
      group, nurses do not receive education as part of the intervention, but may be
      trained by nominated key nurses who have received a short train-the-trainer
      module. All other components are similar to the first intervention group. The
      control group receives the printed study material only. Overall, 120 nursing
      homes including approximately 10,800 residents will be recruited and randomly
      assigned to one of the three groups. The primary outcome is defined as the
      proportion of residents with at least one physical restraint after 12 months
      follow-up. The use of physical restraints will be assessed by direct observation.
      Secondary outcomes are the residents' quality of life and safety parameters, e.g.
      falls and fall-related fractures. In addition, comprehensive process and economic
      evaluations will be performed. CONCLUSIONS: We expect a clinically relevant
      reduction in the proportion of residents with physical restraints. It is also
      expected that the process outcomes of this trial will enrich the knowledge about
      facilitators and barriers for the implementation of the multicomponent
      intervention programme. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02341898.

PMID- 26195249
TI  - Inter-Anastomosis Drainage Tube Between the Pancreas and Jejunum: A Novel
      Technique for Preventing Pancreatic Fistula after Pancreaticoduodenectomy.

PMID- 26195250
TI  - Reduction in Venous Thromboembolism Events: Trauma Performance Improvement and
      Loop Closure Through Participation in a State-Wide Quality Collaborative.
AB  - BACKGROUND: The Michigan Trauma Quality Improvement Program (MTQIP) is a
      collaborative quality initiative sponsored by Blue Cross Blue Shield of Michigan
      and Blue Care Network (BCBSM/BCN). The MTQIP benchmark reports identified our
      trauma center as a high outlier for venous thromboembolism (VTE) episodes. This
      study outlines the performance improvement (PI) process used to reduce the rate
      of VTE using MTQIP infrastructure. STUDY DESIGN: Trauma patients admitted for >
      24 hours, with an Injury Severity Score (ISS) >= 5, were included in this study.
      We performed a preliminary analysis examining prophylaxis drug type to VTE,
      adjusted by patient confounders and timing of first dose, using MTQIP data
      abstracted for our hospital. It showed that patients receiving enoxaparin had a
      VTE rate that was half that of those receiving unfractionated heparin (odds ratio
      0.46, 95% CI 0.25 to 0.85). Guided by these results, we produced the following
      plan: consolidation to single VTE prophylaxis agent and dose, focused education
      of providers, initiation of VTE prophylaxis for all patients-with clear exception
      rules-and dose withholding minimization. Results were monitored using the MTQIP
      platform. RESULTS: After implementation of our focused PI plan, the VTE rate
      decreased from 6.2% (n = 36/year) to 2.6% (n = 14/year). Our trauma center
      returned to average performance status within MTQIP. CONCLUSIONS: Participation
      in MTQIP provided identification of trauma center outlier status for the outcome
      of VTE. Analysis of MTQIP data allowed creation of a local action plan. The MTQIP
      infrastructure supported execution and monitoring of the action plan consistent
      with loop-closure practices, as advocated by the American College of Surgeons
      Committee on Trauma, and a positive performance improvement result was achieved
      with VTE reduction.

PMID- 26195251
TI  - Indocyanine Green Fluorescent Imaging for Hepatic Resection of the Right Hepatic
      Vein Drainage Area.

PMID- 26195253
TI  - The Social Value of Knowledge and International Clinical Research.
AB  - In light of the growth in the conduct of international clinical research in
      developing populations, this paper seeks to explore what is owed to developing
      world communities who host international clinical research. Although existing
      paradigms for assigning and assessing benefits to host communities offer valuable
      insight, I criticize their failure to distinguish between those benefits which
      can justify the conduct of research in a developing world setting and those which
      cannot. I argue that the justification for human subjects research is
      fundamentally grounded in the social value of knowledge, and that this value is
      context-dependent in a manner which should inform our ethical evaluation of the
      conduct of research in specific settings. I propose a new framework for the
      assessment of research benefits assigned to developing world host communities, a
      natural implication of which is to limit the types of research projects which may
      permissibly be conducted in developing world settings. 

PMID- 26195252
TI  - Comparison of kinetic strategies for avoidance of an obstacle with either the
      paretic or non-paretic as leading limb in persons post stroke.
AB  - The task of stepping over obstacles is known to be particularly risky for persons
      post stroke. A kinetic analysis informing on the movement strategies used to
      ensure clearance of the leading limb over an obstacle is, however, lacking. We
      examined obstacle avoidance strategies in six community dwelling stroke survivors
      comparing the use of paretic and non-paretic limb as the leading limb for
      clearance over obstacles measuring 7.5% and 15% of their total leg length.
      Subjects were able to increase foot clearance height in both limbs in order to
      avoid the two obstacles. Obstacle clearance with the non-paretic limb leading was
      associated with positive knee flexor work that increased when stepping over each
      obstacle, thus showing a normal knee strategy that flexes both the knee and the
      hip for foot clearance. There was also slightly increased hip flexor contribution
      for non-paretic obstacle clearance that was the same for both obstacle heights.
      When the paretic limb led during obstacle clearance, there was also evidence of
      an increased knee flexor moment, suggesting a residual knee strategy, but it was
      less pronounced than for the non-paretic limb and was assisted by greater
      vertical hip elevation and additional positive hip flexor work that both gained
      greater importance with increased obstacle height. These findings suggest that
      rehabilitation should explore the ability to improve the residual, but less
      powerful, knee flexor strategy in the paretic limb in specific patients, with
      further promotion of a hip flexor and limb elevation strategy depending on
      patient deficits and obstacle height. 

PMID- 26195254
TI  - Biomechanical properties of the atlantoaxial joint with naturally-occurring
      instability in a toy breed dog. A comparative descriptive cadaveric study.
AB  - The biomechanical properties of the atlanto-axial joint in a young Yorkshire
      Terrier dog with spontaneous atlantoaxial instability were compared to those of
      another young toy breed dog with a healthy atlantoaxial joint. The range-of
      motion was increased in flexion and lateral bending in the unstable joint. In
      addition, lateral bending led to torsion and dorsal dislocation of the axis
      within the atlas. On gross examination, the dens ligaments were absent and a
      longitudinal tear of the tectorial membrane was observed. These findings suggest
      that both ventral and lateral flexion may lead to severe spinal cord compression,
      and that the tectorial membrane may play a protective role in some cases of
      atlantoaxial instability. 

PMID- 26195255
TI  - Disarming smiles: irrelevant happy faces slow post-error responses.
AB  - When we make errors, we tend to experience a negative emotional state. In
      addition, if our errors are witnessed by other people, we might expect those
      observers to respond negatively. However, little is known about how implicit
      social feedback like facial expressions influences error processing. We explored
      this using the cognitive control phenomenon of post-error slowing: the tendency
      to slow the response immediately following an error. Adult participants performed
      a difficult perceptual task: estimating which of two lines (horizontal or
      vertical) was longer. The background showed an irrelevant distractor face with a
      happy, sad, or neutral expression. Participants slowed after errors only when the
      subsequent distractor face was happy, but not when the subsequent distractor was
      sad or neutral nor when a happy face followed a correct response. This suggests
      that information about others' affect, even non-interactive, task-irrelevant
      information, has performance- and valence-dependent effects on adaptive cognitive
      control. 

PMID- 26195257
TI  - Headache: Chronic migraine linked to reduced antioxidant capacity.

PMID- 26195258
TI  - Neuro-oncology: What is the optimal use of bevacizumab in glioblastoma?

PMID- 26195259
TI  - Epilepsy: New insights into the treatment and consequences of poststroke
      epilepsy.

PMID- 26195260
TI  - Neurodegenerative disease: Multiple system atrophy-new insight from prospective
      studies.

PMID- 26195256
TI  - Clearance systems in the brain-implications for Alzheimer disease.
AB  - Accumulation of toxic protein aggregates-amyloid-beta (Abeta) plaques and
      hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease
      (AD). Abeta accumulation has been hypothesized to result from an imbalance
      between Abeta production and clearance; indeed, Abeta clearance seems to be
      impaired in both early and late forms of AD. To develop efficient strategies to
      slow down or halt AD, it is critical to understand how Abeta is cleared from the
      brain. Extracellular Abeta deposits can be removed from the brain by various
      clearance systems, most importantly, transport across the blood-brain barrier.
      Findings from the past few years suggest that astroglial-mediated interstitial
      fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a
      larger portion of extracellular Abeta (eAbeta) clearance than previously thought.
      The meningeal lymphatic vessels, discovered in 2015, might provide another
      clearance route. Because these clearance systems act together to drive eAbeta
      from the brain, any alteration to their function could contribute to AD. An
      understanding of Abeta clearance might provide strategies to reduce excess Abeta
      deposits and delay, or even prevent, disease onset. In this Review, we describe
      the clearance systems of the brain as they relate to proteins implicated in AD
      pathology, with the main focus on Abeta. 

PMID- 26195262
TI  - Rethinking poster presentations at large-scale scientific meetings - is it time
      for the format to evolve?

PMID- 26195264
TI  - Reply to a Letter to the Editor: Bariatric Surgery in Class I Obesity. A Position
      Statement from the International Federation for the Surgery of Obesity and
      Metabolic Disorders (IFSO)--Obesity Surgery 2014;24:487-519.

PMID- 26195263
TI  - Insights into collective cell behaviour from populations of coupled chemical
      oscillators.
AB  - Biological systems such as yeast show coordinated activity driven by chemical
      communication between cells. Here, we show how experiments with coupled chemical
      oscillators can provide insights into collective behaviour in cellular systems.
      Two methods of coupling the oscillators are described: exchange of chemical
      species with the surrounding solution and computer-controlled illumination of a
      light-sensitive catalyst. The collective behaviour observed includes
      synchronisation, dynamical quorum sensing (a density dependent transition to
      population-wide oscillations), and chimera states, where oscillators
      spontaneously split into coherent and incoherent groups. At the core of the
      different types of behaviour lies an intracellular autocatalytic signal and an
      intercellular communication mechanism that influences the autocatalytic growth. 

PMID- 26195261
TI  - A novel method of consensus pan-chromosome assembly and large-scale comparative
      analysis reveal the highly flexible pan-genome of Acinetobacter baumannii.
AB  - BACKGROUND: Infections by pan-drug resistant Acinetobacter baumannii plague
      military and civilian healthcare systems. Previous A. baumannii pan-genomic
      studies used modest sample sizes of low diversity and comparisons to a single
      reference genome, limiting our understanding of gene order and content. A
      consensus representation of multiple genomes will provide a better framework for
      comparison. A large-scale comparative study will identify genomic determinants
      associated with their diversity and adaptation as a successful pathogen. RESULTS:
      We determine draft-level genomic sequence of 50 diverse military isolates and
      conduct the largest bacterial pan-genome analysis of 249 genomes. The pan-genome
      of A. baumannii is open when the input genomes are normalized for diversity with
      1867 core proteins and a paralog-collapsed pan-genome size of 11,694 proteins. We
      developed a novel graph-based algorithm and use it to assemble the first
      consensus pan-chromosome, identifying both the order and orientation of core
      genes and flexible genomic regions. Comparative genome analyses demonstrate the
      existence of novel resistance islands and isolates with increased numbers of
      resistance island insertions over time, from single insertions in the 1950s to
      triple insertions in 2011. Gene clusters responsible for carbon utilization,
      siderophore production, and pilus assembly demonstrate frequent gain or loss
      among isolates. CONCLUSIONS: The highly variable and dynamic nature of the A.
      baumannii genome may be the result of its success in rapidly adapting to both
      abiotic and biotic environments through the gain and loss of gene clusters
      controlling fitness. Importantly, some archaic adaptation mechanisms appear to
      have reemerged among recent isolates.

PMID- 26195265
TI  - Dipeptidyl peptidase-4 inhibitor sitagliptin improves pancreatic beta-cell
      function in hypertensive diabetic patients treated with angiotensin receptor
      blockers.
AB  - INTRODUCTION: Dipeptidyl peptidase (DPP)-4 inhibitors, a novel oral anti-diabetic
      agents, exert a protective effect on pancreatic beta-cell function in patients
      with type 2 diabetic mellitus (T2DM). However, their beneficial effect in
      hypertensive T2DM patients treated with angiotensin receptor blockers (ARBs) has
      not been investigated. METHODS: In this open-label multicenter randomized study,
      a total of 55 hypertensive T2DM patients treated with ARBs were randomly assigned
      to receive the DPP-4 inhibitor sitagliptin or sulfonylurea (SU). RESULTS: After
      24 weeks of treatment, a significant reduction in fasting blood glucose was only
      observed in the sitagliptin group, while HbA1c was significantly reduced in both
      groups. Homeostasis model assessment of insulin resistance was not significantly
      improved in either group. Indicators of pancreatic beta-cell function, including
      proinsulin to insulin ratio and homeostasis model assessment of beta-cell
      function, were significantly improved in the sitagliptin group, but not in the SU
      group. The beneficial effects of sitagliptin were observed in hypoglycemic drug
      naive patients, but not in patients who had received SU monotherapy prior to the
      study. CONCLUSION: Treatment with the DPP-4 inhibitor sitagliptin might exert
      beneficial effects on pancreatic beta-cell function in ARB-treated T2DM patients
      and its efficacy might be more pronounced in hypoglycemic drug naive patients.

PMID- 26195266
TI  - Possible prevention of dialysis-requiring congestive heart failure by angiotensin
      II receptor blockers in non-dialysis Japanese patients with Stage 5 chronic
      kidney disease.
AB  - BACKGROUND: Preventive medications for dialysis-requiring congestive heart
      failure (CHF) in non-dialysis Japanese patients with Stage 5 chronic kidney
      disease (CKD) are unknown. Our aim was to explore which CKD medication was
      associated with a reduced prevalence of dialysis-requiring CHF in non-dialysis
      Japanese patients with Stage 5 CKD. METHODS: The present multicenter,
      retrospective, cross-sectional study examined the association between CKD
      medications and the prevalence of dialysis-requiring CHF in non-dialysis Japanese
      patients with Stage 5 CKD. RESULTS: There were 1536 Japanese Stage 5 CKD patients
      who satisfied our inclusion criteria. We had 309 (20.1%) patients whom had
      developed dialysis-requiring CHF and 940 patients (60.8%) whom had been using
      angiotensin-II receptor blockers (ARBs) before initiating dialysis. In our
      multivariate analysis, only ARB use was significantly associated with a lower
      risk of CHF (Odds ratio (OR): 0.680, 95% confidence interval (CI): 0.516-0.897; p
      = 0.0064), of the CKD treatments examined in this study. CONCLUSIONS: We found
      that ARB use during the pre-dialysis period is associated with a lower prevalence
      of CHF in the non-dialysis Japanese patients with Stage 5 CKD, suggesting a
      possible prevention of dialysis-requiring CHF by ARBs, in non-dialysis Japanese
      patients with Stage 5 CKD.

PMID- 26195267
TI  - Association of ACE insertion or deletion polymorphisms with the risk of coronary
      restenosis after percutaneous coronary intervention: A meta-analysis.
AB  - OBJECTIVE: Previous case-control studies on the relationship between the
      angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms
      and coronary restenosis did not reach the same conclusion. In the present study,
      we aimed to further evaluate the relationship between the ACE gene I/D
      polymorphisms and coronary restenosis, after percutaneous coronary intervention
      (PCI). METHODS: By searching PubMed, EMBase, the Chinese Biomedical Literature
      Database and Wanfang database, we selected 16 case-control studies related to ACE
      gene I/D polymorphism and coronary restenosis after PCI. To test for
      heterogeneity in each study, we utilized the Q-test and I(2) test. To merge the
      odds ratio (OR) and 95% CI, we utilized the random effects model during the
      analyses. RESULTS: The present study included 4693 subjects: 1241 patients with
      coronary restenosis and 3452 without coronary restenosis. By meta-analysis, we
      found there was significant association of ACE gene I/D polymorphism with
      coronary restenosis (D allele versus I allele: OR = 1.92; 95% CI (1.40-2.43); p <
      0.001). A subgroup analysis, by stratification according to ethnicity, also
      showed that this association was found not only in the Caucasian population ((D
      allele versus I allele: OR = 1.94; 95% CI (1.38-2.80); p < 0.001)), but also in
      the Asian population ((D allele versus I allele: OR = 1.83; 95% CI (1.05-3.20); p
      = 0.03)). After stratification according to age, we found that the D allele
      carriers have a higher risk for development of coronary restenosis in subjects <
      60 years old (OR = 2.13; 95% CI: 1.40-3.24; p = 0.0004); while in the subjects ?
      60 years old, the association was present with bordering significance (OR = 1.48;
      95%CI: 0.98-2.25; p = 0.06). CONCLUSIONS: The present study suggested that the
      ACE gene I/D polymorphism was associated with coronary restenosis, regardless of
      age and ethnicity.

PMID- 26195269
TI  - Autoimmune haemolytic anaemia occurring during ibrutinib therapy for chronic
      lymphocytic leukaemia.

PMID- 26195268
TI  - Angiotensin type 1 receptor mediates renal production and conversion of
      prostaglandins E2 to F2alpha in conscious diabetic rats.
AB  - INTRODUCTION: Previous studies demonstrated that stimulation of angiotensin
      subtype 1 receptor (AT1R) led to increased renal generation of prostaglandins E2
      (PGE2) and renal inflammation. In turn, PGE2 increases AT1R activity. The
      conversion of PGE2 to the less active metabolite prostaglandin F2alpha
      (PGF2alpha) via 9-ketoreductase interrupts this feedback loop. The effects of
      diabetes on the interface between AT1R, PGE2 and PGF2alpha are not well
      established. We hypothesized that in diabetes, an aberrant AT1R activity enhances
      the biosynthesis of PGE2 and impairs the activity of PGE 9-ketoreductase, leading
      to accumulation of PGE2. MATERIALS AND METHODS: Using microdialysis technique, we
      monitored renal interstitial fluid levels of angiotensin II (Ang II), PGE2 and
      PGF2alpha in control and AT1R blocker, valsartan, treated diabetic rats (N=8
      each). We utilized the PGF2alpha to PGE2 ratio as indirect measure of PGE 9
      ketoreductase activity. RESULTS: Diabetes increased renal interstitial fluid
      levels of Ang II, PGE2 and PGF2alpha. PGF2alpha/PGE2 ratio increased by the third
      week, but declined by the sixth week of diabetes. Valsartan reduced PGE2 and
      PGF2alpha levels and increased Ang II and the conversion of PGE2 to PGF2alpha.
      CONCLUSION: Our results suggest that in diabetes, AT1R increases PGE2 generation
      and reduces conversion of PGE2 to PGF2alpha with the progression of diabetes.

PMID- 26195270
TI  - Services for people with communication disability in Fiji: barriers and drivers
      of change.
AB  - CONTEXT: The World Health Organization's World report on disability calls upon
      all nations to 'remove the barriers which prevent [people with disabilities] from
      participating in their communities; getting a quality education, finding decent
      work, and having their voices heard' (p. 5). People with communication disability
      (PWCD), as a consequence of their atypical communication, may be more likely to
      be excluded from society, and denied their basic human rights, than other people
      with disability. Fiji, a multicultural and multilingual nation in the south
      western Pacific Ocean, has limited services for PWCD. Service providers in Fiji
      include disability care workers, special education teachers, traditional healers,
      and a small number of visiting volunteer speech-language pathologists. This paper
      outlines the historical and current barriers to, and drivers of change for,
      service development for PWCD in Fiji. ISSUES: Five barriers to service
      development for PWCD in Fiji were identified. (1) A major structural barrier is
      the small population size to develop appropriate infrastructure including
      professional education programs. (2) Geographical barriers include the dispersed
      geography across 300 islands, low population density, the rural-urban divide, and
      risk of disaster from cyclones and flooding. (3) Linguistic diversity, while
      culturally important, can present a barrier to the provision of quality services
      that are available in the languages spoken by PWCD. (4) Cultural barriers include
      historical political instability, although Fiji has become more stable due to the
      recent democratic elections. The social climate affects development of services
      that are appropriate for different dominant cultural groups. (5) Financial
      barriers include low gross domestic product, low financial security and low human
      development index; however, the financial outlook for Fiji is steadily improving
      due to the change in political stability. LESSONS LEARNED: Three levels of
      drivers of change were identified. Macro-level drivers included Fiji's
      endorsement of international policy and increased globalisation (eg tourism).
      Meso-level drivers of change included receipt of foreign aid and support from
      international non-government organisations, development of disability-inclusive
      legislation and policy within Fiji, and strengthening of government policies that
      support disabled people's organisations. Micro-level drivers of change included
      establishment of disabled people's organisations by consumers, adoption of
      disability-inclusive policy and procedures by service providers, and changes in
      the perceptions of disability within the general community. Fijian prevalence
      data confirms that there is an underserved population of PWCD in need of
      specialist services. Significant advocacy work in the disability field by Fijian
      and international disabled people's organisations has led to the Fiji government
      signing international policy (eg Convention on the Rights of Peoples with
      Disabilities), inclusion of disability rights in national legislation (eg 2013
      Constitution of Fiji Islands) and localised policy and practice documentation (eg
      inclusive education policy by the Fiji Islands Ministry of Education). Continued
      service development is required if Fijians with communication disability are to
      have their needs met. The drivers of change at all levels are positioned well to
      overcome current barriers to change; however, a coordinated approach including
      macro-, meso-, and micro-level drivers is required to ensure the future
      development of adequate services for PWCD in Fiji.

PMID- 26195271
TI  - Infrared evaluation of the heat-sink bipolar diathermy dissection technique.
AB  - BACKGROUND: The use of the bipolar diathermy dissection technique is widespread
      amongst surgeons performing flap perforator dissection and microvascular surgery.
      The 'heat-sink' modification uses a DeBakey forcep as a heat sinking
      interposition between the bipolar tip and the main (vascular or flap) pedicle
      aiming to protect it from the thermal effects of the bipolar diathermy. This
      study examines the thermal effects of bipolar cautery upon the microvasculature
      and investigates the efficacy of heat sinking as a thermally protective technique
      in microsurgical dissection. METHODS: A chicken thigh microsurgical training
      model was used to examine the effects of bipolar cautery. The effects of bipolar
      were examined using high definition, real-time infrared thermographic imaging
      (FLIR Systems) and temperature quantitatively assessed at various distances away
      from the point of bipolar cautery. Comparison was made using the heat sink
      technique to determine if it conferred a thermoprotective effect compared to the
      standard technique without heat sink. RESULTS: Using paired t-test analysis
      (SPSS) the heat sink modification of the bipolar dissection technique was found
      to have a highly statistically significant effect (P < 0.000000001) in reducing
      the conductive temperature along the vascular pedicle. This protective effect
      kept temperatures comparable to controls. CONCLUSION: Bipolar cautery is an
      extremely safe method of electrosurgery, however when its use is required within
      3 mm of important vascular architecture, the heat-sink method is a viable and
      easy technique to prevent thermal spread and limit potential coagulopathic
      changes.

PMID- 26195272
TI  - Failed hypospadias repair: An algorithm for secondary reconstruction using
      remaining local tissue.
AB  - Salvage hypospadias surgery is performed after failed primary reconstruction.
      Several treatment strategies have been suggested, all with pros and cons. The aim
      of this study was to evaluate our treatment algorithm for primary hypospadias
      repair applied to secondary cases in which a salvage procedure is indicated and,
      most importantly, local tissue is present. The algorithm was applied to 36
      consecutive patients who had undergone a total of 109 surgical procedures before
      referral. In accordance with the algorithm, 12 patients without ventral curvature
      achieved a satisfactory result with one procedure by the use of local skin flaps.
      Six patients with moderate ventral curvature underwent orthoplasty, fistula
      closure, and/or urethral reconstruction using local skin flaps in one session.
      Eighteen patients with a severe ventral curvature or a proximal meatus were
      reconstructed in two stages using Byars' technique. After a median of two salvage
      procedures (range: 1-4), all patients but one, who awaits splitting of a skin
      bridge in the meatus, were successfully reconstructed. Two patients in active
      follow-up have potential problems requiring further surgery. Our findings
      indicate that failed hypospadias repairs are often due to an underestimation of
      the ventral curvature at the initial repair. Therefore, reevaluation of the
      degree of curvature is important. One-stage salvage repairs can be used, provided
      that none or minimal curvature remains. In cases of marked curvature, however, a
      meticulous resection of the chordee and ventral scarring is crucial. The
      subsequent repair of the large ventral defect and the long urethral
      reconstruction can, in most cases, be safely managed in a two-stage procedure. 

PMID- 26195273
TI  - Hemorrhagic effects of oral anticoagulants: a comparative study between vitamin K
      antagonists (VKA) and direct oral anticoagulants (DOA).

PMID- 26195274
TI  - Ethylphenidate: availability, patterns of use, and acute effects of this novel
      psychoactive substance.
AB  - PURPOSE: Ethylphenidate is a novel psychoactive substance that is an analogue of
      methylphenidate. This paper describes its availability, patterns of use, and
      acute effects. METHODS: Searches of the scientific and grey literature (publicly
      accessible Internet resources) were undertaken, using the keywords
      "Ethylphenidate", "Ethyl phenidate", "Ethyl phenyl(piperidin-2-yl)acetate", and
      "Nopaine", to identify information on the prevalence and patterns of use, desired
      effects, and toxicity of ethylphenidate. An Internet snapshot survey was
      performed on 10 February 2015 to provide information on availability and cost of
      ethylphenidate. RESULTS: The literature search identified 1 case series of acute
      recreational ethylphenidate toxicity, 1 case report of ethylphenidate dependence,
      1 qualitative analysis of user reports on Internet drug forums, 2 conference
      abstracts for surveillance studies, 1 report of two cases of ethylphenidate
      detected in post-mortem analyses, and 198 user reports on Internet discussion
      forums and social media sites. The Internet snapshot survey found 83 websites
      selling ethylphenidate, with purchase prices ranging from L28.20 +/- 0.63 (?37.71
      +/- 0.85) per gram for a 500-mg amount to L2.64 +/- 0.57 (?3.53 +/- 0.77) per
      gram for 1 kg. The published cases and Internet user reports suggest the acute
      effects of ethylphenidate are similar to other stimulant drugs; the most common
      route of use was by nasal insufflation. The most common desired effects were
      euphoria, stimulation, and increased concentration, sociability, and energy
      levels; the most common unwanted effects included anxiety, palpitations,
      insomnia, and paranoia. CONCLUSION: This review of the scientific and grey
      literature has demonstrated that the acute harms associated with its use are
      stimulant in nature and that ethylphenidate is widely available to users over the
      Internet, with significant discounts for bulk purchases.

PMID- 26195276
TI  - An Analog of electrically induced transparency via surface delocalized modes.
AB  - We demonstrate theoretically and experimentally an interesting opaque state,
      which is based on an analog of electromagnetically induced transparency (EIT) in
      mechanism, in a metal hole array of the dimer lattice. By introducing a small
      difference to the dimer holes of each unit cell, the surface delocalized modes
      launching out from the dimer holes can have destructive interferences.
      Consequently, a narrow opaque window in the transparent background can be
      observed in the transmission spectrum. This surface-mode-induced opacity (SMIO)
      state is very sensitive to the difference of the dimer holes, which will promise
      various applications. 

PMID- 26195275
TI  - Meta-Analysis of the Prognostic Impact of Stroke Volume, Gradient, and Ejection
      Fraction After Transcatheter Aortic Valve Implantation.
AB  - The prognostic implications of several baseline preprocedural variables in
      patients with severe native valve aortic stenosis (AS) undergoing transcatheter
      aortic valve implantation (TAVI) are unclear. The goal of this study was to
      determine the impact of reduced stroke volume index (SVI), low gradient (LG), and
      reduced ejection fraction (EF) on all-cause mortality. We searched MEDLINE,
      CENTRAL, EMBASE, Web of Science, and Scopus through October 13, 2014. We
      evaluated the association between low SVI (<35 ml/m(2)), LG (<40 mm Hg), and low
      EF (<50% and <30%) on 1-year all-cause mortality. We pooled results across
      studies using the random-effects model. We included 16 studies at moderate risk
      of bias enrolling 7,673 patients with severe AS who underwent TAVI. Low EF was
      associated with increased 1-year mortality after TAVI compared to preserved EF
      (for EF <30%, hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.19 to 2.16,
      I(2) = 32%; and for EF <50%, HR 1.52, 95% CI 1.31 to 1.76, I(2) = 17%). LG was
      associated with increased mortality after TAVI compared to high mean gradient
      (>=40 mm Hg; HR 1.60, 95% CI 1.30 to 1.97, I(2) = 36%). Low SVI was associated
      with increased mortality after TAVI compared to normal SVI (HR 1.59, 95% CI 1.23
      to 2.05, I(2) = 27%). In conclusion, low SVI, LG, and low EF are each associated
      with higher mortality after TAVI. These findings highlight the importance of
      including these variables into TAVI risk algorithms and will better inform shared
      decision-making before TAVI. 

PMID- 26195277
TI  - Critical Requirements for Rapid Charging of Rechargeable Al- and Li-Ion
      Batteries.

PMID- 26195279
TI  - [Complications and outcomes in the elderly with intracranial meningioma].
AB  - OBJECT: Surgical treatment in patients older than 70 years old with intracranial
      meningioma is still subject to controversy. The benefit/risk ratio of this
      surgery has not been assessed due to the lack of objective criteria. The aim of
      this study is to assess the surgical complications and outcomes in elderly
      patients in our centre. METHOD: A retrospective analysis was performed on
      patients with intracranial meningioma between January 2010 and March 2014. The
      incidence of post-surgical complications, as well as their associated risk
      factors, was also analysed. Functional outcomes were compared with Glasgow
      Outcome Scale and Karnofsky index with those who underwent surgery and those with
      conservative management. Finally, a comparison was made between patients younger
      than 70 years old operated on for intracranial meningioma. RESULTS: A total of 48
      patients diagnosed with intracranial meningioma older than 70 years old, of which
      37 were operated on and 11 were followed up with conservative management. There
      were no differences between the groups in neurological status at discharge
      (Glasgow Outcome Scale 5 67.6 vs. 72.2%, respectively). No differences were
      observed in functional outcome during 6 months of follow up in the Karnofsky
      index between surgical and non-surgical patients (P=.486). In the comparison
      between older and younger than 70 years old, there were no differences in the
      incidence of surgical complications (P=.64 in early complications and P=.23 in
      late complications). CONCLUSION: The results of the present study suggest that
      age should not be a limitation in surgical indications in patients older than 70
      years old with intracranial meningioma. No statistical differences were found in
      functional status compared with conservative management or in surgical
      complications between younger and elderly patients.

PMID- 26195278
TI  - Low-grade inflammation in symptomatic knee osteoarthritis: prognostic value of
      inflammatory plasma lipids and peripheral blood leukocyte biomarkers.
AB  - OBJECTIVE: Inflammatory mediators, such as prostaglandin E2 (PGE2 ) and
      interleukin-1beta (IL-1beta), are produced by osteoarthritic (OA) joint tissue,
      where they may contribute to disease pathogenesis. We undertook the present study
      to examine whether inflammation, evidenced in plasma and peripheral blood
      leukocytes (PBLs), reflects the presence, progression, or specific symptoms of
      symptomatic knee OA. METHODS: Patients with symptomatic knee OA were enrolled in
      a 24-month prospective study of radiographic progression. Standardized knee
      radiographs were obtained at baseline and 24 months. At baseline, levels of the
      plasma lipids PGE2 and 15-hydroxyeicosatetraenoic acid (15-HETE) were measured,
      and transcriptome analysis of PBLs was performed by microarray and quantitative
      polymerase chain reaction. RESULTS: Baseline PGE2 synthase (PGES) levels
      determined by PBL microarray gene expression and plasma PGE2 levels distinguished
      patients with symptomatic knee OA from non-OA controls (area under the receiver
      operating characteristic curve [AUC] 0.87 and 0.89, respectively, P < 0.0001).
      Baseline plasma 15-HETE levels were significantly elevated in patients with
      symptomatic knee OA versus non-OA controls (P < 0.0195). In the 146 patients who
      completed the 24-month study, elevated baseline expression of IL-1beta, tumor
      necrosis factor alpha, and cyclooxygenase 2 (COX-2) messenger RNA in PBLs
      predicted higher risk of radiographic progression as evidenced by joint space
      narrowing (JSN). In a multivariate model, AUC point estimates of models
      containing COX-2 in combination with demographic traits overlapped the confidence
      interval of the base model in 2 of the 3 JSN outcome measures (JSN >0.0 mm, JSN
      >0.2 mm, and JSN >0.5 mm; AUC 0.62-0.67). CONCLUSION: The inflammatory plasma
      lipid biomarkers PGE2 and 15-HETE identify patients with symptomatic knee OA, and
      the PBL inflammatory transcriptome identifies a subset of patients with
      symptomatic knee OA who are at increased risk of radiographic progression. These
      findings may reflect low-grade inflammation in OA and may be useful as diagnostic
      and prognostic biomarkers in clinical development of disease-modifying OA drugs.

PMID- 26195280
TI  - [Normal variations in lingual soft tissue].

PMID- 26195281
TI  - [Primitive cutaneous neuroectodermal tumour].

PMID- 26195282
TI  - Amphiregulin confers trastuzumab resistance via AKT and ERK activation in HER2
      positive breast cancer.
AB  - PURPOSE: Human epidermal growth factor receptor 2 (HER2) heterodimerizes and
      shares common signaling pathways with epidermal growth factor receptor (EGFR). In
      this study, we investigated the clinical implication of amphiregulin, a ligand
      for EGFR, on trastuzumab therapy in HER2-positive breast cancer. METHODS: Serum
      amphiregulin levels were quantified in 50 consecutive patients with HER2-positive
      metastatic breast cancer who received first-line trastuzumab plus taxane
      chemotherapy between October 2004 and July 2009. In addition, in vitro
      experiments were carried out to validate the results. RESULTS: The median serum
      amphiregulin level was 1.0 ng/mL with a maximum level of 4.4 ng/mL. Patients with
      high serum amphiregulin levels (>=0.5 ng/mL) had significantly shorter
      progression-free survival (15.1 months vs. not reached; P = 0.018). Colony
      forming assays demonstrated that the addition of amphiregulin resulted in
      increased proliferation of cells. In addition, the anti-proliferative effect of
      trastuzumab was decreased in the presence of amphiregulin. Western blot analysis
      showed that amphiregulin activated AKT and ERK pathways. In addition, in the
      presence of amphiregulin, sustained phosphorylation of AKT and ERK pathways was
      observed after trastuzumab treatment. CONCLUSIONS: High serum amphiregulin levels
      were associated with early disease progression in these patients, possibly due to
      AKT and ERK signaling activation by amphiregulin.

PMID- 26195283
TI  - Residue-specific structures and membrane locations of pH-low insertion peptide by
      solid-state nuclear magnetic resonance.
AB  - The pH-low insertion peptide (pHLIP) binds to a membrane at pH 7.4 unstructured
      but folds across the bilayer as a transmembrane helix at pH~6. Despite their
      promising applications as imaging probes and drug carriers that target cancer
      cells for cytoplasmic cargo delivery, the mechanism of pH modulation on pHLIP
      membrane interactions has not been completely understood. Here, we show the first
      study on membrane-associated pHLIP using solid-state NMR spectroscopy. Data on
      residue-specific conformation and membrane location describe pHLIP in various
      surface-bound and membrane-inserted states at pH 7.4, 6.4 and 5.3. The critical
      membrane-adsorbed state is more complex than previously envisioned. At pH 6.4,
      for the major unstructured population, the peptide sinks deeper into the membrane
      in a state II' that is distinct from the adsorbed state II observed at pH 7.4,
      which may enable pHLIP to sense slight change in acidity even before insertion. 

PMID- 26195284
TI  - Methane Emissions from the Natural Gas Transmission and Storage System in the
      United States.
AB  - The recent growth in production and utilization of natural gas offers potential
      climate benefits, but those benefits depend on lifecycle emissions of methane,
      the primary component of natural gas and a potent greenhouse gas. This study
      estimates methane emissions from the transmission and storage (T&S) sector of the
      United States natural gas industry using new data collected during 2012,
      including 2,292 onsite measurements, additional emissions data from 677
      facilities and activity data from 922 facilities. The largest emission sources
      were fugitive emissions from certain compressor-related equipment and "super
      emitter" facilities. We estimate total methane emissions from the T&S sector at
      1,503 [1,220 to 1,950] Gg/yr (95% confidence interval) compared to the 2012
      Environmental Protection Agency's Greenhouse Gas Inventory (GHGI) estimate of
      2,071 [1,680 to 2,690] Gg/yr. While the overlap in confidence intervals indicates
      that the difference is not statistically significant, this is the result of
      several significant, but offsetting, factors. Factors which reduce the study
      estimate include a lower estimated facility count, a shift away from engines
      toward lower-emitting turbine and electric compressor drivers, and reductions in
      the usage of gas-driven pneumatic devices. Factors that increase the study
      estimate relative to the GHGI include updated emission rates in certain emission
      categories and explicit treatment of skewed emissions at both component and
      facility levels. For T&S stations that are required to report to the EPA's
      Greenhouse Gas Reporting Program (GHGRP), this study estimates total emissions to
      be 260% [215% to 330%] of the reportable emissions for these stations, primarily
      due to the inclusion of emission sources that are not reported under the GHGRP
      rules, updated emission factors, and super-emitter emissions. 

PMID- 26195285
TI  - Antiangiogenic activity of herboxidiene via downregulation of vascular
      endothelial growth factor receptor-2 and hypoxia-inducible factor-1alpha.
AB  - Antiangiogenesis is now thought of as one of the most important approaches for
      anticancer therapy. In this study, we determined the antiangiogenic property of
      herboxidiene, a polyketide natural product. Herboxidiene effectively inhibited
      the proliferation of human umbilical vein endothelial cells (HUVECs) at
      concentrations not exhibiting cytotoxicity. Furthermore, the natural product
      significantly suppressed vascular endothelial growth factor-induced invasion and
      tube formation in HUVECs as well as neovascularization of the chorioallantoic
      membrane in developing chick embryos. We also identified an association between
      the antiangiogenic activity of herboxidiene and the downregulation of both the
      phosphorylation of VEGF receptor 2 (KDR/Flk-1) and the expression of hypoxia
      inducible factor-1alpha at the transcriptional level. These results suggest that
      herboxidiene functions as a potential antiangiogenic agent and may be applicable
      for anticancer therapy by targeting tumor angiogenesis. 

PMID- 26195286
TI  - Organelle-specific Hsp90 inhibitors.
AB  - Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone that is
      involved in the folding, activation, and stabilization of numerous oncogenic
      proteins. It has become an attractive therapeutic target, especially for
      eradicating malignant cancers and overcoming chemotherapy resistance. The Hsp90
      family in mammalian cells is composed of four major homologs: Hsp90alpha,
      Hsp90beta, 94-kDa glucose-regulated protein (Grp94), and TNF receptor-associated
      protein 1 (Trap1). Hsp90alpha and Hsp90beta are mainly localized in the
      cytoplasm, while Grp94 and Trap1 reside in the endoplasmic reticulum and the
      mitochondria, respectively. Additionally, some Hsp90 s are secreted from the
      cytoplasm, commonly called extracellular Hsp90. Interestingly, each Hsp90 isoform
      is localized in a particular organelle, possesses a unique biological function,
      and participates in various physiological and pathological processes. To inhibit
      the organelle-specific Hsp90 chaperone function, there have been significant
      efforts to accumulate Hsp90 inhibitors in particular cellular compartments. This
      review introduces current studies regarding the delivery of Hsp90 inhibitors to
      subcellular organelles, particularly to the extracellular matrix and the
      mitochondria, and discusses their biological insights and therapeutic
      implications. 

PMID- 26195287
TI  - Brain structural and microstructural alterations associated with cerebral palsy
      and motor impairments in adolescents born extremely preterm and/or extremely low
      birthweight.
AB  - AIM: To elucidate neurobiological changes underlying motor impairments in
      adolescents born extremely preterm (gestation <28wks) and/or with extremely low
      birthweight (ELBW, <1000g), our aims were the following: (1) to compare
      corticospinal tract (CST) microstructure and primary motor cortex (M1) volume,
      area, and thickness between extremely preterm/ELBW adolescents and a comparison
      group with normal birthweight (>2499g); (2) to compare CST microstructure and M1
      volume, area, and thickness between extremely preterm/ELBW adolescents with
      cerebral palsy (CP), motor impairment without CP, and no motor impairment; and
      (3) to investigate associations between CST microstructure and M1 measures.
      METHOD: This study used diffusion and structural magnetic resonance imaging to
      examine the CST and M1 in a geographical cohort of 191 extremely preterm/ELBW
      adolescents (mean age 18y 2.4mo [SD 9.6mo]; 87 males, 104 females) and 141
      adolescents in the comparison group (mean age 18y 1.2mo [SD 9.6mo]; 59 males, 82
      females). RESULTS: Extremely preterm/ELBW adolescents had higher CST axial,
      radial, and mean diffusivities and lower M1 thickness than the comparison group.
      Extremely preterm/ELBW adolescents with CP had higher CST diffusivities than non
      motor-impaired extremely preterm/ELBW adolescents. CST diffusivities correlated
      with M1 volume and area. INTERPRETATION: Extremely preterm/ELBW adolescents have
      altered CST microstructure, which is associated with CP. Furthermore, the results
      elucidate how CST and M1 alterations interrelate to potentially influence motor
      function in extremely preterm/ELBW adolescents.

PMID- 26195288
TI  - Redox regulation of the MED28 and MED32 mediator subunits is important for
      development and senescence.
AB  - Mediator is a conserved multi-protein complex that acts as a bridge between
      promoter-bound transcriptional regulators and RNA polymerase II. While redox
      signaling is important in adjusting plant metabolism and development, the
      involvement of Mediator in redox homeostasis and regulation only recently started
      to emerge. Our previous results show that the MED10a, MED28, and MED32 Mediator
      subunits form various types of covalent oligomers linked by intermolecular
      disulfide bonds in vitro. To link that with biological significance we have
      characterized Arabidopsis med32 and med28 mutants and found that they are
      affected in root development and senescence, phenotypes possibly associated to
      redox changes. 

PMID- 26195290
TI  - 22q11.2 deletion syndrome presenting with early-onset Parkinson's disease.

PMID- 26195291
TI  - Retraction Note to: A randomized phase II study of everolimus for advanced
      pancreatic neuroendocrine tumors in Chinese patients.

PMID- 26195289
TI  - Migration, Health Care Behaviors, and Primary Care for Rural Latinos with
      Diabetes.
AB  - Many US Latinos migrate or travel between the US and Mexico on a regular basis,
      defined as circular migration. Latinos with diabetes (n = 250) were surveyed
      about circular migration and their ability to use medications and perform
      recommended diabetes self-care activities. A review of medical charts was
      performed. Twenty-eight percent (n = 70) of patients traveled to Mexico during
      the last 12 months. Older Latinos were more likely to report traveling to Mexico
      and back into the US. Among those that traveled, 29 % reported use of less
      medication than they wanted to or were prescribed because of travel and 20 % ran
      out of medications. The rate of reported problem areas while traveling were 39 %
      (27/70) for following a diabetic diet, 31 % (21/70) for taking medication, and 37
      % (26/70) for glucose self-monitoring. The results suggest that the structure of
      primary care and care coordination are important for this population to fully
      engage in diabetes self-care.

PMID- 26195292
TI  - The effect of young age on survival in breast cancer: early results.

PMID- 26195293
TI  - Heregulin and HER3 are prognostic biomarkers in oropharyngeal squamous cell
      carcinoma.
AB  - BACKGROUND: Although heregulin and human epidermal growth factor receptor 3
      (HER3) are frequently expressed at high levels in patients with head and neck
      cancer, their prognostic value remains unclear. The authors explored the
      prognostic significance of heregulin/HER3 expression in patients with
      oropharyngeal squamous cell carcinoma (OPSCC), taking into account other HER
      family members as well as p16 status. METHODS: Ninety-six primary tumor specimens
      from patients with OPSCC were retrospectively collected and analyzed for
      heregulin messenger RNA (mRNA) using in situ hybridization and for HER3,
      epidermal growth factor receptor, and human epidermal growth factor receptor 2
      (HER2) using quantitative immunohistochemistry. Heregulin and HER3 mRNA levels
      were also examined among different tumor types using The Cancer Genome Atlas
      database. RESULTS: High heregulin mRNA (> the median) correlated significantly
      with poor overall survival (OS) (hazard ratio [HR], 8.48; 95% confidence interval
      [95% CI], 2.17-33.17 [P =.002]) but not disease-free survival (HR, 1.52; 95% CI,
      0.64-3.65 [P =.341]) in patients with OPSCC. Heregulin mRNA correlated negatively
      with OS in both patients with p16-positive (P =.049) and p16-negative (P =.091)
      OPSCC on univariate analysis. High HER3 (> the median) also correlated with poor
      OS (HR, 4.68; 95% CI, 1.47-14.90 [P =.009]) on multivariate analysis. Epidermal
      growth factor receptor levels independently correlated with disease-free survival
      (P =.025) and inversely correlated with p16 status (P =.012). In addition, The
      Cancer Genome Atlas data demonstrated that head and neck squamous cell carcinoma
      exhibits higher heregulin expression compared with other solid tumor types
      examined. CONCLUSIONS: High heregulin mRNA and high HER3 protein levels were
      found to independently correlate with poor OS in patients with OPSCC. These data
      support targeting HER3 in patients with heregulin-high OPSCC and warrant further
      clinical investigation.

PMID- 26195294
TI  - Assessing effects of prenatal alcohol exposure using group-wise sparse
      representation of fMRI data.
AB  - Task-based fMRI activation mapping has been widely used in clinical neuroscience
      in order to assess different functional activity patterns in conditions such as
      prenatal alcohol exposure (PAE) affected brains and healthy controls. In this
      paper, we propose a novel, alternative approach of group-wise sparse
      representation of the fMRI data of multiple groups of subjects (healthy control,
      exposed non-dysmorphic PAE and exposed dysmorphic PAE) and assess the systematic
      functional activity differences among these three populations. Specifically, a
      common time series signal dictionary is learned from the aggregated fMRI signals
      of all three groups of subjects, and then the weight coefficient matrices (named
      statistical coefficient map (SCM)) associated with each common dictionary were
      statistically assessed for each group separately. Through inter-group comparisons
      based on the correspondence established by the common dictionary, our
      experimental results have demonstrated that the group-wise sparse coding strategy
      and the SCM can effectively reveal a collection of brain networks/regions that
      were affected by different levels of severity of PAE. 

PMID- 26195295
TI  - Successful antidepressant chronotherapeutics enhance fronto-limbic neural
      responses and connectivity in bipolar depression.
AB  - The identification of antidepressant response predictors in bipolar disorder (BD)
      may provide new potential enhancements in treatment selection. Repeated total
      sleep deprivation combined with light therapy (TSD+LT) can acutely reverse
      depressive symptoms and has been proposed as a model antidepressant treatment.
      This study aims at investigating the effect of TSD+LT on effective connectivity
      and neural response in cortico-limbic circuitries during implicit processing of
      fearful and angry faces in patients with BD. fMRI and Dynamic Causal Modeling
      (DCM) were combined to study the effect of chronotherapeutics on neural responses
      in healthy controls (HC, n = 35) and BD patients either responder (RBD, n = 26)
      or non responder (nRBD, n = 11) to 3 consecutive TSD+LT sessions. Twenty-four
      DCMs exploring connectivity between anterior cingulate cortex (ACC), dorsolateral
      prefrontal cortex (DLPFC), Amygdala (Amy), fusiform gyrus and visual cortex were
      constructed. After treatment, patients significantly increased their neural
      responses in DLPFC, ACC and insula. nRBD showed lower baseline and endpoint
      neural responses than RBD. The increased activity in ACC and in medial prefrontal
      cortex, associated with antidepressant treatment, was positively associated with
      the improvement of depressive symptomatology. Only RBD patients increased
      intrinsic connectivity from DLPFC to ACC and reduced the modulatory effect of the
      task on Amy-DLPFC connection. A successful antidepressant treatment was
      associated with an increased functional activity and connectivity within cortico
      limbic networks, suggesting the possible role of these measures in providing
      possible biomarkers for treatment efficacy.

PMID- 26195296
TI  - Neural correlates of response inhibition in children with attention
      deficit/hyperactivity disorder: A controlled version of the stop-signal task.
AB  - The stop-signal task has been used extensively to investigate the neural
      correlates of inhibition deficits in children with ADHD. However, previous
      findings of atypical brain activation during the stop-signal task in children
      with ADHD may be confounded with attentional processes, precluding strong
      conclusions on the nature of these deficits. In addition, there are recent
      concerns on the construct validity of the SSRT metric. The aim of this study was
      to control for confounding factors and improve the specificity of the stop-signal
      task to investigate inhibition mechanisms in children with ADHD. FMRI was used to
      measure inhibition related brain activation in 17 typically developing children
      (TD) and 21 children with ADHD, using a highly controlled version of the stop
      signal task. Successful inhibition trials were contrasted with control trials
      that were comparable in frequency, visual presentation and absence of motor
      response. We found reduced brain activation in children with ADHD in key
      inhibition areas, including the right inferior frontal gyrus/insula, and anterior
      cingulate/dorsal medial prefrontal cortex. Using a more stringent controlled
      design, this study replicated and specified previous findings of atypical brain
      activation in ADHD during motor response inhibition. 

PMID- 26195297
TI  - Sex differences in abnormal white matter development associated with conduct
      disorder in children.
AB  - Associations between white matter pathway abnormalities and antisocial
      personality disorder in adults are well replicated, and there is some evidence
      for an association of white matter abnormalities with conduct disorder (CD) in
      adolescents. In this study, white matter maturation using diffusion tensor
      imaging (DTI) was examined in 110 children aged 10.0 +/- 0.8 years selected to
      vary widely in their numbers of CD symptoms. The results replicated age-related
      increases in fractional anisotropy (FA) found in previous studies. There was not
      a significant association between the number of CD symptoms and FA, but CD
      symptoms were found to be significantly associated with greater axial and radial
      diffusivity in a broad range of white matter tracts, particularly in girls. In
      complementary analyses, there were similar significant differences in axial and
      radial diffusivity between children who met diagnostic criteria for CD and
      healthy children with no symptoms of CD, particularly in girls. Brain structural
      abnormalities may contribute to the emergence of CD in childhood, perhaps playing
      a greater role in girls.

PMID- 26195299
TI  - Inspection of notch depths in thin structures using transmission coefficients of
      laser-generated Lamb waves.
AB  - The non-contact feature of the Laser/EMAT ultrasonic (LEU) technique is
      attractive for its NDT applications. However, it is challenging to apply it in
      thin structures because of the difficulties in the signal interpretations. In
      this work, the LEU technique is used to inspect the notch depths in thin steel
      plates. A Continuous Wavelet Transform (CWT)-based algorithm is developed to
      calculate the transmission coefficients of laser-generated Lamb waves. The effect
      of varying notch depths on Lamb waves' transmission coefficients is investigated
      both numerically and experimentally. The transmission coefficients of laser
      generated Lamb waves calculated using CWT have been used successfully to predict
      the notch depths in thin structures. 

PMID- 26195298
TI  - Nonfunctional ingestion of plant miRNAs in silkworm revealed by digital droplet
      PCR and transcriptome analysis.
AB  - Since a plant miRNA (miR168) cross-regulating a mammalian transcript was
      reported, miRNA-mediated cross-kingdom communication has become one of the most
      compelling but controversial topics. In the present study, we used silkworm and
      mulberry, which is a model for studies on the interactions between the insect and
      its host plant, to address whether miRNA-mediated cross-kingdom communication is
      a common phenomenon. The results of TA clone, Sanger sequencing and droplet
      digital PCR demonstrated that several mulberry-derived miRNAs could enter to
      silkworm hemolymph and multiple tested tissues. Synthetic miR166b was also
      detected in hemolymph and fat body. However, the ingestion of synthetic miR166b
      did not play roles in silkworm physiological progress, which was revealed by RNA
      seq analyses, RT-PCR, and phenotypic investigations. Mulberry miRNAs are
      convincingly transferred to the silkworm orally and no physiological process
      associated with the miRNAs was demonstrable. The results provided a new aspect of
      cross-kingdom miRNA transfer. 

PMID- 26195300
TI  - Measuring Transition Readiness: A Correlational Study of Perceptions of Parent
      and Adolescents and Young Adults with Sickle Cell Disease.
AB  - Adolescents and young adults (AYAs) often transfer from pediatric to adult care
      without adequate preparation, resulting in increased morbidity and mortality. The
      purpose of this descriptive research study of parent/AYA dyads was to measure
      perceptions of transition readiness. Factors that were found to be associated
      with perceptions of increased readiness to transition included AYA age, the
      amount of responsibility AYAs assume for their healthcare and the degree of
      parent involvement. More attention should be focused on these aspects of care to
      improve transition from pediatric to adult care for AYAs with sickle cell
      disease. 

PMID- 26195301
TI  - Concept Analysis of Health Care Transition in Adolescents with Chronic
      Conditions.
AB  - Children with chronic conditions are living into adulthood and present with
      unique needs. One such need is their transition from pediatric to adult health
      care. This paper examined the literature to analyze and synthesize the concept of
      transition within two contexts, health care and adolescents with chronic
      conditions. Fifty multidisciplinary sources were included for analysis. A
      refined, working definition of the concept of health care transition in
      adolescents with chronic conditions is presented. Results will enable the
      scientific community to discuss salient issues using well-defined, uniform
      terminology. Nursing implications are delineated to ensure that these youths
      thrive into adulthood. 

PMID- 26195303
TI  - The Gut Microbiota of Termites: Digesting the Diversity in the Light of Ecology
      and Evolution.
AB  - Termite guts harbor a dense and diverse microbiota that is essential for
      symbiotic digestion. The major players in lower termites are unique lineages of
      cellulolytic flagellates, whereas higher termites harbor only bacteria and
      archaea. The functions of the mostly uncultivated lineages and their distribution
      in different diet groups are slowly emerging. Patterns in community structure
      match changes in the biology of different host groups and reflect the
      availability of microbial habitats provided by flagellates, wood fibers, and the
      increasing differentiation of the intestinal tract, which also creates new niches
      for microbial symbionts. Whereas the intestinal communities in the closely
      related cockroaches seem to be shaped primarily by the selective forces of
      microhabitat and functional niche, the social behavior of termites reduces the
      stochastic element of community assembly, which facilitates coevolution and may
      ultimately result in cospeciation. 

PMID- 26195302
TI  - Physical Activity Among Adolescents with Cerebral Palsy: An Integrative Review.
AB  - PROBLEM: Physical activity is necessary for optimum physical and psychosocial
      health in the general population. It is even more important for adolescents who
      struggle with impairments that limit motor function. Recommendations for best
      practice are needed as adolescents transition into adulthood. PURPOSE: An
      integrative review was performed to determine the state of the science regarding
      1) what factors impact physical activity in adolescents with cerebral palsy, and
      2) how the needs of this population have been addressed regarding physical
      activity. SEARCH STRATEGY: A literature search of MEDLINE, CINAHL, and PubMed was
      conducted using the terms cerebral palsy, mobility or activity, and adolescents.
      Exclusion criteria were surgical or pharmacological interventions. RESULTS OF THE
      LITERATURE SEARCH: Descriptive and intervention studies were included and
      evaluated for purpose, design, and key findings. SYNTHESIS OF EVIDENCE:
      Correcting the decline of physical activity in adolescents with CP may carry
      benefits over into adulthood. There are few studies that adapt physical activity
      to age and level of impairment. Several studies support approaching physical
      activity from a social model, focusing on participation of the person in the
      context of environment. There is a lack of research incorporating family-centered
      care. Many study designs are shallow and lack the proper instruments for
      assessing outcomes. IMPLICATIONS FOR PRACTICE: Home and community based
      interventions need to be developed that are individualized. More studies are
      needed with stronger research designs and better instruments in order to
      generalize results for practice.

PMID- 26195304
TI  - Perception and Homeostatic Control of Iron in the Rhizobia and Related Bacteria.
AB  - Iron is an essential nutrient, but it can also be toxic. Therefore, iron
      homeostasis must be strictly regulated. Transcriptional control of iron-dependent
      gene expression in the rhizobia and other taxa of the Alphaproteobacteria is
      fundamentally different from the Fur paradigm in Escherichia coli and other model
      systems. Rather than sense iron directly, the rhizobia employ the iron response
      regulator (Irr) to monitor and respond to the status of an iron-dependent
      process, namely, heme biosynthesis. This novel control mechanism allows iron
      homeostasis to be integrated with other cellular processes, and it permits
      differential control of iron regulon genes in a manner not readily achieved by
      Fur. Moreover, studies of Irr have defined a role for heme in conditional protein
      stability that has been subsequently described in eukaryotes. Finally, Irr
      mediated control of iron metabolism may reflect a cellular strategy that
      accommodates a greater reliance on manganese. 

PMID- 26195305
TI  - Anthrax Pathogenesis.
AB  - Anthrax is caused by the spore-forming, gram-positive bacterium Bacillus
      anthracis. The bacterium's major virulence factors are (a) the anthrax toxins and
      (b) an antiphagocytic polyglutamic capsule. These are encoded by two large
      plasmids, the former by pXO1 and the latter by pXO2. The expression of both is
      controlled by the bicarbonate-responsive transcriptional regulator, AtxA. The
      anthrax toxins are three polypeptides-protective antigen (PA), lethal factor
      (LF), and edema factor (EF)-that come together in binary combinations to form
      lethal toxin and edema toxin. PA binds to cellular receptors to translocate LF (a
      protease) and EF (an adenylate cyclase) into cells. The toxins alter cell
      signaling pathways in the host to interfere with innate immune responses in early
      stages of infection and to induce vascular collapse at late stages. This review
      focuses on the role of anthrax toxins in pathogenesis. Other virulence
      determinants, as well as vaccines and therapeutics, are briefly discussed. 

PMID- 26195306
TI  - Microsporidia: Eukaryotic Intracellular Parasites Shaped by Gene Loss and
      Horizontal Gene Transfers.
AB  - Microsporidia are eukaryotic parasites of many animals that appear to have
      adapted to an obligate intracellular lifestyle by modifying the morphology and
      content of their cells. Living inside other cells, they have lost many, or all,
      metabolic functions, resulting in genomes that are always gene poor and often
      very small. The minute content of microsporidian genomes led many to assume that
      these parasites are biochemically static and uninteresting. However, recent
      studies have demonstrated that these organisms can be surprisingly complex and
      dynamic. In this review I detail the most significant recent advances in
      microsporidian genomics and discuss how these have affected our understanding of
      many biological aspects of these peculiar eukaryotic intracellular pathogens. 

PMID- 26195307
TI  - Comment on: "Energetics and Kinetics of Thermal Ionization Models of MALDI" by
      Richard Knochenmuss. J. Am. Soc. Mass Spectrom. 25, 1521-1527 (2014).

PMID- 26195308
TI  - CycloBranch: De Novo Sequencing of Nonribosomal Peptides from Accurate Product
      Ion Mass Spectra.
AB  - Nonribosomal peptides have a wide range of biological and medical applications.
      Their identification by tandem mass spectrometry remains a challenging task. A
      new open-source de novo peptide identification engine CycloBranch was developed
      and successfully applied in identification or detailed characterization of 11
      linear, cyclic, branched, and branch-cyclic peptides. CycloBranch is based on
      annotated building block databases the size of which is defined by the user
      according to ribosomal or nonribosomal peptide origin. The current number of
      involved nonisobaric and isobaric building blocks is 287 and 521, respectively.
      Contrary to all other peptide sequencing tools utilizing either peptide libraries
      or peptide fragment libraries, CycloBranch represents a true de novo sequencing
      engine developed for accurate mass spectrometric data. It is a stand-alone and
      cross-platform application with a graphical and user-friendly interface; it
      supports mzML, mzXML, mgf, txt, and baf file formats and can be run in parallel
      on multiple threads. It can be downloaded for free from
      http://ms.biomed.cas.cz/cyclobranch/ , where the User's manual and video
      tutorials can be found.

PMID- 26195309
TI  - Endoscopic Resection of Malignant Colonic Polyps: Why Clinicopathological
      Correlation (CPC) Is Needed for Optimal Treatment of CRC?

PMID- 26195310
TI  - EUS Diagnostic Criteria for Chronic Pancreatitis: A Comparison of Conventional
      Versus Rosemont Criteria.
AB  - OBJECTIVE: To compare the Rosemont criteria, which are graded features chosen by
      experts in 2007, versus the conventional criteria, which require >= 3-5 of the 9
      features that are "counted as equal," for the diagnosis of chronic pancreatitis
      by EUS. METHODS: This is a retrospective cohort study. EUS examinations were
      scored using both criteria, and the following categories compared: 3-CC versus
      "consistent with" chronic pancreatitis by RC; 3-CC versus "consistent with" and
      "suggestive of" chronic pancreatitis by RC; 5-CC versus "consistent with" chronic
      pancreatitis by RC; and 5-CC versus "consistent with" and "suggestive of" chronic
      pancreatitis by RC. RESULTS: There was a statistically significant difference
      between 3-CC and RC, either "consistent with" alone or both "consistent with" and
      "suggestive of" (p < 0.0001). Comparing 5-CC and "consistent with" showed a
      statistical difference (p = 0.0014), but no difference comparing 5-CC to
      "consistent with" and "suggestive of." CONCLUSION: CC diagnose more cases of
      chronic pancreatitis than RC when using 3-CC or when comparing 5-CC to
      "consistent with" chronic pancreatitis by Rosemont, indicating that the Rosemont
      criteria are more stringent.

PMID- 26195311
TI  - Hepatitis C Virus Infection Increases the Risk of Developing Chronic Kidney
      Disease: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND RATIONALE: Chronic kidney disease and hepatitis C virus are
      prevalent in the general population worldwide, and controversy exists about the
      impact of HCV infection on the development and progression of kidney disease.
      DESIGN: A systematic review of the published medical literature was made to
      assess whether positive anti-HCV serologic status plays an independent impact on
      the development of chronic kidney disease in the adult general population. We
      used a random-effects model to generate a summary estimate of the relative risk
      of chronic kidney disease (defined by reduced glomerular filtration rate or
      detectable proteinuria) with HCV across the published studies. Meta-regression
      and stratified analysis were also conducted. RESULTS: Twenty-three studies (n =
      2,842,421 patients) were eligible, and separate meta-analyses were performed
      according to the outcome. Pooling results of longitudinal studies (n = 9;
      1,947,034 unique patients) demonstrated a relationship between positive HCV
      serologic status and increased incidence of chronic kidney disease, the summary
      estimate for adjusted hazard ratio was 1.43 (95% confidence interval 1.23; 1.63,
      P = 0.0001), and between-studies heterogeneity was noted (P value by Q test
      <0.0001). The risk of the incidence of chronic kidney disease associated with
      HCV, in the subset of Asian surveys, was 1.31 (95% confidence interval 1.16;
      1.45) without heterogeneity (P value by Q test = 0.6). HCV positive serology was
      an independent risk factor for proteinuria; adjusted odds ratio, 1.508 (95%
      confidence intervals 1.19; 1.89, P = 0.0001) (n = 6 studies; 107,356 unique
      patients). CONCLUSIONS: HCV infection is associated with an increased risk of
      developing chronic kidney disease in the adult general population.

PMID- 26195312
TI  - Novel Colitis Immunotherapy Targets Bin1 and Improves Colon Cell Barrier
      Function.
AB  - BACKGROUND: Ulcerative colitis (UC) is associated with defects in colonic
      epithelial barriers as well as inflammation of the colon mucosa resulting from
      the recruitment of lymphocytes and neutrophils in the lamina propria. Patients
      afflicted with UC are at increased risk of colorectal cancer. Currently, UC
      management employs general anti-inflammatory strategies associated with a variety
      of side effects, including heightened risks of infection, in patients where the
      therapy is variably effective. Thus, second generation drugs that can more
      effectively and selectively limit UC are desired. AIM: Building on genetic
      evidence that attenuation of the Bin1 (Bridging integrator 1) gene can limit UC
      pathogenicity in the mouse, we pursued Bin1 targeting as a therapeutic option.
      METHODS: Mice were injected with a single dose of Bin1 mAb followed by oral
      administration of 3 % DSS in water for 7 days. RESULTS: In this study, we offer
      preclinical proof of concept for a monoclonal antibody (mAb) targeting the Bin1
      protein that blunts UC pathogenicity in a mouse model of experimental colitis.
      Administration of Bin1 mAb reduced colitis morbidity in mice; whereas unprotected
      mice is characterized by severe lesions throughout the mucosa, rupture of the
      lymphoid follicle, high-level neutrophil and lymphocyte infiltration into the
      mucosal and submucosal areas, and loss of surface crypts. In vitro studies in
      human Caco-2 cells showed that Bin1 antibody altered the expression of tight
      junction proteins and improved barrier function. CONCLUSIONS: Our results suggest
      that a therapy based on Bin1 monoclonal antibody supporting mucosal barrier
      function and protecting integrity of the lymphoid follicle could offer a novel
      strategy to treat UC and possibly limit risks of colorectal cancer.

PMID- 26195313
TI  - Individuals with Primary Sclerosing Cholangitis Have Elevated Levels of
      Biomarkers for Apoptosis but Not Necrosis.
AB  - BACKGROUND AND AIM: Hepatocyte apoptosis or necrosis from accumulation of bile
      salts may play an important role in the disease progression of primary sclerosing
      cholangitis (PSC). The aim of the current study was to measure serum markers of
      hepatocyte apoptosis (cytokeratin-18 fragments--K18) and necrosis (high-mobility
      group protein B1--HMGB1) in adults with PSC and examine the relationship with
      disease severity. METHODS: We measured serum levels of K18 and HMGB1 in well
      phenotyped PSC (N = 37) and 39 control subjects (N = 39). Severity of PSC was
      assessed biochemically, histologically, and PSC Mayo risk score. Quantification
      of hepatocyte apoptosis was performed using TUNEL assay. RESULTS: The mean age of
      the study cohort was 49.7 +/- 13.3 years and comprised of 67% men and 93%
      Caucasian. Serum K18 levels were significantly higher in the PSC patients
      compared to control (217.4 +/- 78.1 vs. 157.0 +/- 58.2 U/L, p = 0.001). However,
      HMGB1 levels were not different between the two groups (5.38 +/- 2.99 vs. 6.28 +/
      2.85 ng/mL, p = 0.15). Within the PSC group, K18 levels significantly correlated
      with AST (r = 0.5, p = 0.002), alkaline phosphatase (r = 0.5, p = 0.001), total
      bilirubin (r = 0.61, p <= 0.001), and albumin (r = -0.4, p = 0.02). Serum K18
      levels also correlated with the level of apoptosis present on the liver biopsy (r
      = 0.8, p <= 0.001) and Mayo risk score (r = 0.4, p = 0.015). CONCLUSION: Serum
      K18 but not HMGB1 levels were increased in PSC and associated with severity of
      underlying liver disease and the degree of hepatocyte apoptosis.

PMID- 26195314
TI  - Pisa syndrome in progressive supranuclear palsy: A case report.

PMID- 26195315
TI  - Developmental Toxicity and Fertility Assessment in Rabbits with Tabalumab: A
      Human IgG4 Monoclonal Antibody.
AB  - Tabalumab is a human immunoglobulin G subclass 4 monoclonal antibody that has
      been under development for autoimmune disorders. Tabalumab has full neutralizing
      activity against both soluble and membrane B-cell activating factor, a B-cell
      survival factor. The objectives of these studies were to assess the effects of
      tabalumab on embryo-fetal development and on male (M) and female (F) fertility in
      rabbits, a pharmacologically relevant species. Doses were administered at 0
      (vehicle control), 0.3 (embryo-fetal study only), 1.0, and 30 mg/kg. In the
      embryo-fetal study, pregnant rabbits does were given a single dose by intravenous
      injection on gestation day (GD) 7. In the fertility studies, tabalumab was
      administered by intravenous injection every 7 days starting 2 (F) or 4 (M) weeks
      before mating, during cohabitation, and until necropsy (M) or through GD 18 (F).
      Treated animals were mated with untreated partners. Parental clinical signs, body
      weight, food consumption, blood lymphocyte phenotyping, organ weights,
      morphologic pathology, ovarian and uterine observations, sperm parameters, and
      fertility indices were evaluated along with conceptus viability, weight, and
      morphology. Exposure assessments were made in all main study animals and
      satellite animals. No adverse parental, reproductive, or developmental effects
      were observed in any study at any dose. A pharmacodynamic response consisting of
      dose-dependent decreases in the percent and number of total B lymphocytes and
      increases in the percent and/or number of total T lymphocytes was observed in
      parental rabbits at 1.0 and 30 mg/kg. In conclusion, no adverse reproductive or
      developmental effects were observed in rabbits following exposure to tabalumab at
      doses as high as 30 mg/kg and exposures at least 14-fold greater than human
      exposure levels.

PMID- 26195316
TI  - Suspected cancer (part 2--adults): reference tables from updated NICE guidance.

PMID- 26195317
TI  - Reliability and validity of the Cancer Therapy Satisfaction Questionnaire in lung
      cancer.
AB  - PURPOSE: To test the reliability and validity of the Cancer Treatment
      Satisfaction Questionnaire (CTSQ), to assess its relation with quality of life
      (QoL), and to assess the interpretability of the domain scores in lung cancer
      patients receiving intravenous chemotherapy. METHODS: Patients with stage IIIB
      and IV non-squamous non-small cell lung carcinoma treated with pemetrexed were
      enrolled in our study. They completed the 16-item CTSQ and two other (health
      related) QoL questionnaires. Information about sociodemographic characteristics,
      cancer stage, and the experience of adverse events was collected. Internal
      consistency, construct validity, and clinical interpretability were calculated.
      RESULTS: Fifty-five patients completed the CTSQ. Correlations of the CTSQ items
      with its domain were all above 0.40. A high correlation between item 8 and the
      expectations of therapy and satisfaction with therapy domain was observed (0.50
      and 0.48, respectively). The CTSQ domains demonstrated good internal consistency
      and low to moderate correlations of the CTSQ with the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire-C30 and World
      Health Organization Quality of Life-BREF. No significant differences in mean
      domain scores were observed in relation to the number and severity of different
      adverse events and chemotherapy-related adverse events. CONCLUSIONS: The Dutch
      version of the CTSQ was found to be a reliable and valid instrument to assess
      satisfaction and expectations of treatment in lung cancer patients receiving
      intravenous chemotherapy. Furthermore, the CTSQ proved to be of additional
      informative value as not all of its domains correlated with the various domains
      of the existing HRQoL instruments.

PMID- 26195318
TI  - The joint subclinical elevation of CRP and IL-6 is associated with lower health
      related quality of life in comparison with no elevation or elevation of only one
      of the biomarkers.
AB  - BACKGROUND: Measures of health-related quality of life (HRQoL), like the Short
      Form (SF)-36, have been suggested to correlate with inflammatory biomarkers. It
      is, however, unclear whether a joint measure of two inflammatory biomarkers would
      bring additional information in comparison with evaluation of one inflammatory
      biomarker. OBJECTIVE: To evaluate associations between SF-36 and low-grade
      inflammation in a Swedish population, with emphasis on a combined measure of C
      reactive protein (CRP) and interleukin-6 (IL-6) as a proxy for low-grade
      inflammation. METHODS: In a randomly selected sample of a middle-aged Swedish
      general population (n = 905; aged 45-69 years, 50% women), relations between SF
      36 parameters and the biomarkers were tested. Regression and correlation analyses
      were adjusted for sex, age, presence of disease, lifestyle, and psychological
      factors. RESULTS: After adjustment for sex and age, HRQoL was significantly lower
      in the group with a joint elevation of CRP and IL-6 in comparison with either the
      group with no elevation or the groups showing elevation of one of the two
      biomarkers. Also after full adjustments, the combined measure of elevated CRP and
      IL-6, with few exceptions, was associated with significantly lower HRQoL in
      comparison with elevations in one of them, difference ranging from 4 (Mental
      Health scale) to 18 scale steps (Role-Physical scale). CONCLUSION: This study
      confirms that there is a relationship between HRQoL and low-grade inflammation.
      In particular, SF-36 scores are significantly lower in a group with joint
      elevation of IL-6 and CRP, in comparison with elevation of either one of them.

PMID- 26195319
TI  - Quality of life and emotional distress in patients and burden in caregivers: a
      comparison between assisted peritoneal dialysis and self-care peritoneal
      dialysis.
AB  - PURPOSE: Assisted peritoneal dialysis (PD) involving caregivers allows more
      patients to get started on home-based dialysis with good clinical outcomes, but
      evidence on patient-reported and caregiver-reported outcomes is lacking. This
      study aimed to compare assisted PD versus self-care PD on quality of life (QoL)
      and psychosocial outcomes for patients and caregivers. The effect of PD modality
      [automated PD (APD); continuous ambulatory PD (CAPD)] in relation to self-care or
      assisted care was also examined. METHODS: A cross-sectional sample of 231 PD
      patients [142 self-care (57 APD/85 CAPD) and 89 assisted care PD (45 APD/44
      CAPD)], 72 caregivers of assisted PD patients and 39 family members of self-care
      PD patients completed the Kidney Disease Quality of Life Short Form (KDQOL-SF),
      World Health Organisation Quality of Life Instrument-brief and the Hospital
      Anxiety and Depression Scale. Caregivers and family members completed the Lay
      Care-Giving for Adults Receiving Dialysis questionnaire and Zarit Burden
      Interview. RESULTS: Case-mix-adjusted comparisons indicated comparable QoL in all
      dimensions with the exception of physical SF-12 (p = .001) and the KDQOL effects
      of kidney disease in favour of self-care PD. Levels of anxiety (9.72 +/- 4.90;
      8.25 +/- 5.22) and depression (8.63 +/- 3.80; 6.35 +/- 4.76) were equivalent in
      assisted PD and self-care PD, respectively. Assisted PD caregivers reported more
      task-orientated duties (p = .007), yet levels of perceived burden were equal to
      those reported by family members of self-care PD. CONCLUSION: Our findings of
      mostly comparable patient and caregiver outcomes in assisted PD and self-care PD
      suggest that caregiver burden and QoL should not be a barrier to using assisted
      PD.

PMID- 26195320
TI  - Deep Brain Stimulation Modulates Gamma Oscillations and Theta-Gamma Coupling in
      Treatment Resistant Depression.
AB  - BACKGROUND: Deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG)
      is becoming an effective therapeutic option for treatment resistant depression
      (TRD). OBJECTIVE/HYPOTHESIS: Identifying the neurophysiological mechanisms
      altered by DBS may lead to more tailored treatment parameters and enhanced
      efficacy. METHODS: Twenty TRD patients with implanted DBS in the SCG were
      recruited. Patients participated in three EEG recording sessions, one with DBS
      ON, one with DBS randomized to ON or OFF, and one with DBS OFF. During each
      session, subjects performed N-back working memory tasks, namely the 0-back and 3
      back. Fourteen subjects with valid EEG were included in the analysis. Changes in
      frontal gamma oscillations (30-50 Hz) and coupling between theta (4-7 Hz) and
      gamma oscillations as a result of DBS stimulation were quantified and correlated
      with depressive symptoms. RESULTS: DBS stimulation resulted in suppression of
      frontal oscillations in the ON state relative to the OFF state during the N-back
      tasks. Greatest suppression was demonstrated in beta and gamma oscillations and
      most pronounced during the 3-back. Suppression of gamma oscillations in the 3
      back correlated with a reduction in depressive symptoms. DBS ON relative to OFF
      in the 3-back also resulted in an increase in theta-gamma coupling that
      correlated with a reduction in depressive symptoms. CONCLUSION: Suppression of
      gamma oscillations and increased theta-gamma coupling through DBS is likely
      mediated by both SCG activation of inhibitory circuits and an enhancement of
      plasticity in the frontal cortex. Activation of both pathways may explain the
      therapeutic properties of DBS in TRD.

PMID- 26195321
TI  - Primary Motor Cortex Excitability During Recovery After Stroke: Implications for
      Neuromodulation.
AB  - BACKGROUND: Non-invasive brain stimulation techniques may be useful adjuvants to
      promote recovery after stroke. They are typically used to facilitate ipsilesional
      cortical excitability directly, or indirectly by suppressing contralesional
      cortical excitability and reducing interhemispheric inhibition from the
      contralesional to ipsilesional hemisphere. However, most of the evidence for this
      approach comes from studies of patients at the chronic stage of recovery.
      HYPOTHESIS: We hypothesized that corticomotor excitability and interhemispheric
      inhibition would initially be asymmetric, with greater interhemispheric
      inhibition from contralesional to ipsilesional M1. We also hypothesized that
      balancing of corticomotor excitability and interhemispheric inhibition would be
      associated with greater improvements in paretic upper-limb impairment and
      function. METHODS: We conducted a retrospective analysis of longitudinal data
      collected from 46 patients during the first six months after stroke. Transcranial
      magnetic stimulation was used to measure rest motor threshold, stimulus-response
      curves, and ipsilateral silent periods from the extensor carpi radialis muscles
      of both upper limbs. Analyses of variance and linear regression modeling were
      used to evaluate the effect of time on corticomotor excitability and
      interhemispheric inhibition in both hemispheres, and associations between these
      effects and improvements in paretic upper-limb impairment and function. RESULTS:
      All participants had subcortical damage and only two had motor cortex
      involvement. As expected, ipsilesional corticomotor excitability was initially
      suppressed and increased over time, and this increase was associated with
      improved upper-limb impairment and function. However, interhemispheric inhibition
      was symmetrical and stable over time, and there was no evidence for a decrease in
      contralesional corticomotor excitability. CONCLUSIONS: Neuromodulation
      interventions applied during spontaneous recovery may be more beneficial if they
      facilitate ipsilesional corticomotor excitability directly.

PMID- 26195322
TI  - Somatostatin receptor 2a is a more sensitive diagnostic marker of meningioma than
      epithelial membrane antigen.

PMID- 26195323
TI  - TERT promoter mutations in primary central nervous system lymphoma are associated
      with spatial distribution in the splenium.

PMID- 26195324
TI  - Counseling in fetal medicine: evidence-based answers to clinical questions on
      morbidly adherent placenta.
AB  - Although the incidence of morbidly adherent placenta (MAP) has risen
      progressively in the last two decades, there remains uncertainty about the
      diagnosis and management of this condition. The aim of this review is to provide
      up-to-date and evidence-based answers to common clinical questions regarding the
      diagnosis and management of MAP. Different risk factors have been associated with
      MAP; however, previous Cesarean section and placenta previa are the most
      frequently associated. Ultrasound is the primary method for diagnosing MAP and
      has a good overall diagnostic accuracy for its detection. When considering the
      different ultrasound signs of MAP, color Doppler seems to provide the best
      diagnostic performance. Magnetic resonance imaging has the same accuracy in
      diagnosing MAP as does ultrasound examination; its use should be considered when
      a resective procedure, such as hysterectomy, is planned as it can provide
      detailed information about the topography of placental invasion and predict
      difficulties that may arise in surgery. The optimal gestational age for delivery
      in pregnancies with MAP is yet to be established; planning surgery between 34 and
      36 weeks of gestation provides the best balance between fetal maturity and the
      risk of unexpected episodes of heavy bleeding, which are more likely to occur
      with delivery after this timepoint, especially in severe cases of MAP. The
      optimal surgical approach to MAP depends on multiple factors, including
      availability of an experienced team, specific surgical skills and hospital
      resources. Copyright (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 26195325
TI  - Scale structure in the Australian lungfish, Neoceratodus forsteri (Osteichthyes:
      Dipnoi).
AB  - Scales of the Australian lungfish, Neoceratodus forsteri, are secreted within the
      dermis by a capsule of scleroblasts, and enclosed in a pouch made of collagen
      fibers, in contact with the epidermis over the posterior third of the scale. Each
      scale grows from a focus, which represents the first formed part of the scale. On
      the internal surface of the scale is elasmodin, made of collagen fiber bundles
      arranged in layers. Elasmodin, unmineralized in N. forsteri, contains cells in
      the living animal, and the number of layers increases as the scales grow.
      Squamulin, on the thin external part of the scale, is also laid down in layers,
      and based on a matrix of fine collagen fibrils, mineralized with a poorly
      crystalline biogenic calcium hydroxylapatite. Squamulin is divided into separate
      sections called squamulae, and contains long tubules with cells applied to the
      wall of the tubule. The anterior and lateral surfaces of the squamulin are
      ornamented with pediculae, and the posterior surface has longitudinal ridges,
      from which collagen fibers extend to anchor the scale within the pouch. Elasmodin
      and squamulin are linked by unmineralized collagen fibrils. The layers, formed at
      irregular intervals, are connected around the margin of the scale, effectively
      converting the whole scale into a flat structure resembling a pearl, with the
      first formed tissues deeply embedded inside the scale, and the youngest on the
      outer surface. Incremental lines in the hard tissue, and the number of layers in
      the elasmodin, do not reflect the chronological age of the fish.

PMID- 26195326
TI  - Temporal branch of the posterior cerebral artery arising from the posterior
      communicating artery diagnosed by MR angiography.
AB  - We report a case in which the temporal branch of the posterior cerebral artery
      (PCA) arose from the posterior communicating artery (PCoA) and was diagnosed by
      magnetic resonance (MR) angiography. The PCoA arose from its normal point on the
      supraclinoid internal carotid artery and fused with the PCA at its normal point
      of the P1-P2 junction. We believe this is the first report of such a variation.
      Careful review of MR angiographic images is important to detect rare arterial
      variations, and partial maximum-intensity-projection images aid their
      identification on MR angiography. 

PMID- 26195327
TI  - Identifying longitudinal trends within EEG experiments.
AB  - Differential brain response to sensory stimuli is very small (a few microvolts)
      compared to the overall magnitude of spontaneous electroencephalogram (EEG),
      yielding a low signal-to-noise ratio (SNR) in studies of event-related potentials
      (ERP). To cope with this phenomenon, stimuli are applied repeatedly and the ERP
      signals arising from the individual trials are averaged at the subject level.
      This results in loss of information about potentially important changes in the
      magnitude and form of ERP signals over the course of the experiment. In this
      article, we develop a meta-preprocessing step utilizing a moving average of ERP
      across sliding trial windows, to capture such longitudinal trends. We embed this
      procedure in a weighted linear mixed effects model to describe longitudinal
      trends in features such as ERP peak amplitude and latency across trials while
      adjusting for the inherent heteroskedasticity created at the meta-preprocessing
      step. The proposed unified framework, including the meta-processing and the
      weighted linear mixed effects modeling steps, is referred to as MAP-ERP (moving
      averaged-processed ERP). We perform simulation studies to assess the performance
      of MAP-ERP in reconstructing existing longitudinal trends and apply MAP-ERP to
      data from young children with autism spectrum disorder (ASD) and their typically
      developing counterparts to examine differences in patterns of implicit learning,
      providing novel insights about the mechanisms underlying social and/or cognitive
      deficits in this disorder. 

PMID- 26195328
TI  - Enhanced Charge Transport in Tantalum Nitride Nanotube Photoanodes for Solar
      Water Splitting.
AB  - In the present work we grow anodic self-organized Ta2O5 nanotube layers, which
      are converted by ammonolysis to Ta3 N5 nanotubes, and then are used as
      photoanodes for photoanalytic water splitting. We introduce a two-step
      anodization process that not only improves order (reduced growth defects) and
      overall light absorption in the nanotube layers, but also provides a
      significantly reduced interface charge resistance at the nitride/metal interface
      due to subnitride (TaNx ) formation. As a result, such nanotube anodes afford a
      15-fold increase of the photocurrent compared with conventional nanotubular Ta3
      N5 electrodes under AM 1.5 G simulated sunlight (100 mW cm(-2)) conditions.

PMID- 26195330
TI  - Visually directed vs. software-based targeted biopsy compared to transperineal
      template mapping biopsy in the detection of clinically significant prostate
      cancer.
AB  - OBJECTIVES: Targeted biopsy based on cognitive or software magnetic resonance
      imaging (MRI) to transrectal ultrasound registration seems to increase the
      detection rate of clinically significant prostate cancer as compared with
      standard biopsy. However, these strategies have not been directly compared
      against an accurate test yet. The aim of this study was to obtain pilot data on
      the diagnostic ability of visually directed targeted biopsy vs. software-based
      targeted biopsy, considering transperineal template mapping (TPM) biopsy as the
      reference test. METHODS AND MATERIALS: Prospective paired cohort study included
      50 consecutive men undergoing TPM with one or more visible targets detected on
      preoperative multiparametric MRI. Targets were contoured on the Biojet software.
      Patients initially underwent software-based targeted biopsies, then visually
      directed targeted biopsies, and finally systematic TPM. The detection rate of
      clinically significant disease (Gleason score >=3+4 and/or maximum cancer core
      length >=4mm) of one strategy against another was compared by 3*3 contingency
      tables. Secondary analyses were performed using a less stringent threshold of
      significance (Gleason score >=4+3 and/or maximum cancer core length >=6mm).
      RESULTS: Median age was 68 (interquartile range: 63-73); median prostate-specific
      antigen level was 7.9ng/mL (6.4-10.2). A total of 79 targets were detected with a
      mean of 1.6 targets per patient. Of these, 27 (34%), 28 (35%), and 24 (31%) were
      scored 3, 4, and 5, respectively. At a patient level, the detection rate was 32
      (64%), 34 (68%), and 38 (76%) for visually directed targeted, software-based
      biopsy, and TPM, respectively. Combining the 2 targeted strategies would have led
      to detection rate of 39 (78%). At a patient level and at a target level, software
      based targeted biopsy found more clinically significant diseases than did
      visually directed targeted biopsy, although this was not statistically
      significant (22% vs. 14%, P = 0.48; 51.9% vs. 44.3%, P = 0.24). Secondary
      analysis showed similar results. Based on these findings, a paired cohort study
      enrolling at least 257 men would verify whether this difference is statistically
      significant. CONCLUSION: The diagnostic ability of software-based targeted biopsy
      and visually directed targeted biopsy seems almost comparable, although utility
      and efficiency both seem to be slightly in favor of the software-based strategy.
      Ongoing trials are sufficiently powered to prove or disprove these findings.

PMID- 26195331
TI  - [Aspects of radiation protection during chest X-radiography].
AB  - BACKGROUND: Radiation safety in conventional X-ray diagnostics is based on the
      concepts of justification, optimization of an X-ray examination and limitation of
      the radiation exposure achieved during the examination. Optimization of an X-ray
      examination has to be considered as a multimodal process in which all technical
      components of the X-ray equipment have to be adapted to each other and also have
      to be adapted to the anthropometric characteristics of patients and the clinical
      indications. OBJECTIVES: In this article the technical components of a
      conventional pediatric chest X-radiograph are presented, and recommendations for
      optimizing chest X-rays in children are provided. RESULTS AND DISCUSSION: The
      following measures are of prime importance: correct x-ray beam limitation, using
      the posteroanterior projection when possible and not using anti-scatter grids in
      children under approximately 8 years old. In pediatric radiology chest x-rays
      that are taken not at the peak of inspiration can also be of some diagnostic
      significance. Optimization of an X-ray examination inevitably results in the
      limitation of radiation exposure.

PMID- 26195329
TI  - Challenges in engineering osteochondral tissue grafts with hierarchical
      structures.
AB  - INTRODUCTION: A major hurdle in treating osteochondral (OC) defects is the
      different healing abilities of two types of tissues involved - articular
      cartilage and subchondral bone. Biomimetic approaches to OC-construct
      engineering, based on recapitulation of biological principles of tissue
      development and regeneration, have potential for providing new treatments and
      advancing fundamental studies of OC tissue repair. AREAS COVERED: This review on
      state of the art in hierarchical OC tissue graft engineering is focused on tissue
      engineering approaches designed to recapitulate the native milieu of cartilage
      and bone development. These biomimetic systems are discussed with relevance to
      bioreactor cultivation of clinically sized, anatomically shaped human
      cartilage/bone constructs with physiologic stratification and mechanical
      properties. The utility of engineered OC tissue constructs is evaluated for their
      use as grafts in regenerative medicine, and as high-fidelity models in biological
      research. EXPERT OPINION: A major challenge in engineering OC tissues is to
      generate a functionally integrated stratified cartilage-bone structure starting
      from one single population of mesenchymal cells, while incorporating perfusable
      vasculature into the bone, and in bone-cartilage interface. To this end, new
      generations of advanced scaffolds and bioreactors, implementation of mechanical
      loading regimens and harnessing of inflammatory responses of the host will likely
      drive the further progress.

PMID- 26195332
TI  - Sudden unexpected death, epilepsy and familial cardiac pathology.
AB  - We evaluated the prevalence of epilepsy in a cohort of patients who suffered a
      sudden unexpected death (SUDEP), and determined the proportion of the deaths that
      were related to an identifiable underlying familial cardiac pathology. Epilepsy
      is common in people who experience a sudden unexpected death, with approximately
      a quarter having identifiable familial electrophysiological abnormalities.
      Familial cardiac pathology may be an important cause of SUDEP. A retrospective
      evaluation was performed of 74 families that were referred to the Royal Melbourne
      Hospital Cardiac Genetic Clinic over a 5 year period for investigation following
      a family member's sudden, presumed cardiac, death. This state-wide referral
      clinic includes all patients who have died from a sudden unexpected death in whom
      the cause of death is unascertained. An epilepsy diagnosis was categorised as
      either definite, probable, possible or unlikely. The family members underwent
      comprehensive clinical evaluations and investigations in an attempt to identify a
      familial cardiac cause for the sudden unexpected death. Our findings suggest that
      systematic referral to a cardiac genetics service is warranted for the first
      degree relatives of people with epilepsy who experience a sudden unexplained
      death, for further evaluation and to identify those who are at higher risk for
      sudden death. Interventions may then be instituted to potentially reduce this
      risk.

PMID- 26195333
TI  - Natural history and treatment of craniocervical junction dural arteriovenous
      fistulas.
AB  - Dural arteriovenous fistulas (DAVFs) located at the craniocervical junction are
      rare vascular malformations with distinctive features, and their natural history
      and the optimal treatment strategy remains unclear. We retrospectively reviewed
      eight patients with craniocervical junction DAVF who were evaluated at our
      institution between 2009 and 2012. We also conducted a MEDLINE search for all
      reports of craniocervical junction DAVF between 1970 and 2013, and reviewed 119
      patients from 56 studies. From a total of 127 patients, 46 (37.1%) presented with
      myelopathy, 53 (43.1%) with subarachnoid hemorrhage (SAH), and four (3.3%) with
      brainstem dysfunction. SAH was typically mild, most often Hunt and Hess Grade I
      or II (83.3%), and associated with ascending venous drainage via the intracranial
      veins (p<0.001). Higher rates of obliteration were observed after microsurgery
      compared to embolization. Overall, younger age (odds ratio [OR] 1.07; 95%
      confidence interval [CI] 1.01-1.12; p=0.011), hemorrhagic presentation (OR 0.17;
      95% CI 0.06-0.50; p=0.001), and microsurgery (OR 0.23; 95% CI 0.08-0.6; p=0.004)
      were independently predictive of good outcome at the last follow-up. Microsurgery
      was the only independent predictor of overall improvement at the last follow-up
      (OR 4.35; 95% CI 1.44-13.2; p=0.009). Prompt diagnosis and microsurgical
      management, offering a greater chance of immediate obliteration, may optimize the
      outcomes for patients with craniocervical junction DAVF. Endovascular treatment
      is often not feasible due to lesion angioarchitecture, and is associated with a
      higher risk of lesion recanalization or recurrence. However, long term studies
      with newer embolic agents such as Onyx (ev3 Endovascular, Plymouth, MN, USA) are
      yet to be performed. 

PMID- 26195334
TI  - Phosphorylated neurofilament subunit levels in the serum of cervical compressive
      myelopathy patients.
AB  - We investigated the serum levels of the phosphorylated form of the high molecular
      weight neurofilament subunit (pNF-H) in patients with cervical compressive
      myelopathy. pNF-H is becoming increasingly recognized as a biomarker for axonal
      injury, however, it remains unclear whether serum pNF-H is elevated in chronic
      spinal cord compression. We examined 26 patients who underwent surgery for
      cervical compressive myelopathy. Peripheral blood samples were obtained both
      preoperatively and 1 week after surgery to evaluate the serum pNF-H levels using
      an enzyme-linked immunosorbent assay. A history of recent aggravation of
      myelopathy was also investigated. Of the 26 myelopathy patients, the preoperative
      serum pNF-H level was negative in 20 patients and moderately elevated in six.
      Patients who were positive for pNF-H were more likely to have had a recent
      aggravation of myelopathy compared with the pNF-H negative patients (83 versus
      25%; p=0.02). All patients who were positive for pNF-H before surgery remained
      positive after surgery. Two patients who became positive after surgery
      demonstrated a neurologic deterioration associated with the surgery. In
      conclusion, the serum pNF-H level was negative in the majority of patients with
      cervical compressive myelopathy. Our results suggest that an elevated serum level
      of pNF-H is associated with an acute worsening of myelopathy and that a positive
      conversion of pNF-H after surgery is a marker of perioperative neural damage.

PMID- 26195335
TI  - What does burst suppression really mean?
AB  - This paper describes the various electroencephalographic (EEG) patterns expressed
      by the comatose brain, starting with the sleep-like oscillations associated with
      light coma. Deeper coma generally displays a burst-suppression pattern
      characterized by alternating episodes of isoelectric (flat) EEG and bursting slow
      waves. The latter are the result of cortical hyperexcitability, as demonstrated
      by intracellular recordings in anesthetized animals. Further deepening of the
      coma yields to continuous isoelectric electroencephalogram and eventually results
      in a newly discovered type of spiky waves that have been termed Nu-complexes. The
      paper discusses the structures participating in the genesis of burst suppression,
      the afferent mechanisms, and the reasons for which this activity should or should
      not be regarded as an epileptic disorder. This article is part of a Special Issue
      entitled "Status Epilepticus". 

PMID- 26195337
TI  - Rheumatoid arthritis: 2014 treat-to-target RA recommendations--strategy is key.
AB  - The treatment recommendations for rheumatoid arthritis (RA) have been updated.
      Among the changes included, rheumatologists are advised to share treatment
      decision-making with patients and to maximize patients' quality of life by aiming
      for clinical remission. The update is based on scientific evidence, but more
      research is needed to strengthen RA treatment strategies.

PMID- 26195341
TI  - Predictors of return to work with upper limb disorders.
AB  - BACKGROUND: Return to work (RTW) is a key goal in the proper management of upper
      limb disorders (ULDs). ULDs stem from diverse medical aetiologies and numerous
      variables can affect RTW. The abundance of factors, their complex interactions
      and the diversity of human behaviour make it difficult to pinpoint those at risk
      of not returning to work (NRTW) and to intervene effectively. AIMS: To weigh
      various clinical, functional and occupational parameters that influence RTW in
      ULD sufferers and to identify significant predictors. METHODS: A retrospective
      analysis of workers with ULD referred to an occupational health clinic and
      further examined by an occupational therapist. Functional assessment included
      objective and subject ive [Disability of the Arm, Shoulder and Hand (DASH) score]
      parameters. Quantification of work requirements was based on definitions from the
      Dictionary of Occupational Titles web site. RTW status was confirmed by a follow
      up telephone questionnaire. RESULTS: Among the 52 subjects, the RTW rate was 42%.
      The DASH score for the RTW group was 27 compared with 56 in the NRTW group (P <
      0.001). In multivariate analyses, only the DASH score was found to be a
      significant independent predictor of RTW (P < 0.05). CONCLUSIONS: Physicians and
      rehabilitation staff should regard a high DASH score as a warning sign when
      assessing RTW prospects in ULD cases. It may be advisable to focus on workers
      with a large discrepancy between high DASH scores and low objective disability
      and to concentrate efforts appropriately.

PMID- 26195338
TI  - Cartilage damage in osteoarthritis and rheumatoid arthritis--two unequal
      siblings.
AB  - Cartilage damage is a key feature of degenerative joint disorders-primarily
      osteoarthritis (OA)-and chronic inflammatory joint diseases, such as rheumatoid
      arthritis (RA). Substantial progress has been made towards understanding the
      mechanisms that lead to degradation of the cartilage matrix in either condition,
      which ultimately results in the progressive remodelling of affected joints. The
      available data have shown that the molecular steps in cartilage matrix breakdown
      overlap in OA and RA. However, they have also, to a great extent, changed our
      view of the roles of cartilage in the pathogenesis of these disorders. In OA,
      cartilage loss occurs as part of a complex programme that resembles aspects of
      embryonic bone formation through endochondral ossification. In RA, early
      cartilage damage is a key trigger of cellular reactions in the synovium. In a
      proposed model of RA as a site-specific manifestation of a systemic autoimmune
      disorder, early cartilage damage in the context of immune activation leads to a
      specific cellular response within articular joints that could explain not only
      the organ specificity of RA, but also the chronic nature and perpetuation of the
      disease. 

PMID- 26195342
TI  - Investigation of the optimal collagen fibre orientation in human iliac arteries.
AB  - The distribution of collagen fibres plays a significant role in the mechanical
      behaviour of artery walls. Experimental data show that in most artery wall layers
      there are two (or more) in-plane symmetrically disposed families of fibres.
      However, a recent investigation revealed that some artery wall layers have only
      one preferred fibre direction, notably in the medial layer of human common iliac
      arteries. This paper aims to provide a possible explanation for this intriguing
      phenomenon. An invariant-based constitutive model is utilized to characterize the
      mechanical behaviour of tissues. We then use three different hypotheses to
      determine the 'optimal fibre angle' in an iliac artery model. All three
      hypotheses lead to the same result that the optimal fibre angle in the medial
      layer of the iliac artery is close to the circumferential direction. The axial
      pre-stretch, in particular, is found to play an essential role in determining the
      optimal fibre angle. 

PMID- 26195343
TI  - Water regime history drives responses of soil Namib Desert microbial communities
      to wetting events.
AB  - Despite the dominance of microorganisms in arid soils, the structures and
      functional dynamics of microbial communities in hot deserts remain largely
      unresolved. The effects of wetting event frequency and intensity on Namib Desert
      microbial communities from two soils with different water-regime histories were
      tested over 36 days. A total of 168 soil microcosms received wetting events
      mimicking fog, light rain and heavy rainfall, with a parallel "dry condition"
      control. T-RFLP data showed that the different wetting events affected desert
      microbial community structures, but these effects were attenuated by the effects
      related to the long-term adaptation of both fungal and bacterial communities to
      soil origins (i.e. soil water regime histories). The intensity of the water
      pulses (i.e. the amount of water added) rather than the frequency of wetting
      events had greatest effect in shaping bacterial and fungal community structures.
      In contrast to microbial diversity, microbial activities (enzyme activities)
      showed very little response to the wetting events and were mainly driven by soil
      origin. This experiment clearly demonstrates the complexity of microbial
      community responses to wetting events in hyperarid hot desert soil ecosystems and
      underlines the dynamism of their indigenous microbial communities. 

PMID- 26195344
TI  - Single-Molecule Visualization of the Activity of a Zn(2+)-Dependent DNAzyme.
AB  - We demonstrate the single-molecule imaging of the catalytic reaction of a Zn(2+)
      dependent DNAzyme in a DNA origami nanostructure. The single-molecule catalytic
      activity of the DNAzyme was examined in the designed nanostructure, a DNA frame.
      The DNAzyme and a substrate strand attached to two supported dsDNA molecules were
      assembled in the DNA frame in two different configurations. The reaction was
      monitored by observing the configurational changes of the incorporated DNA
      strands in the DNA frame. This configurational changes were clearly observed in
      accordance with the progress of the reaction. The separation processes of the
      dsDNA molecules, as induced by the cleavage by the DNAzyme, were directly
      visualized by high-speed atomic force microscopy (AFM). This nanostructure-based
      AFM imaging technique is suitable for the monitoring of various chemical and
      biochemical catalytic reactions at the single-molecule level.

PMID- 26195345
TI  - Assurance of monoclonality in one round of cloning through cell sorting for
      single cell deposition coupled with high resolution cell imaging.
AB  - Regulatory authorities require that cell lines used in commercial production of
      recombinant proteins must be derived from a single cell progenitor or clone. The
      limiting dilution method of cell cloning required multiple rounds of low-density
      cell plating and microscopic observation of a single cell in order to provide
      evidence of monoclonality. Other cloning methods rely on calculating statistical
      probability of monoclonality rather than visual microscopic observation of cells.
      We have combined the single cell deposition capability of the Becton Dickinson
      InfluxTM cell sorter with the microscopic imaging capability of the SynenTec
      Cellavista to create a system for producing clonal production cell lines. The
      efficiency of single cell deposition by the InfluxTM was determined to be 98%
      using fluorescently labeled cells. The centrifugal force required to settle the
      deposited cells to the bottom of the microplate well was established to be 1,126g
      providing a 98.1% probability that all cells will be in the focal plane of the
      Cellavista imaging system. The probability that a single cell was deposited by
      the cell sorter combined with the probability of every cell settling into the
      focal plane of the imager yield a combined >99% probability of documented
      monoclonality.

PMID- 26195346
TI  - [Isolation of Candida spp. from ascites in cirrhotic patients].
AB  - The isolation of Candida spp. in ascites of cirrhotic patients is an uncommon
      situation in clinical practice. Factors that have been associated with increased
      susceptibility to primary fungal peritonitis are exposure to broad-spectrum
      antibiotics and immunosuppression, a typical situation of these patients. We
      report seven episodes of Candida spp. isolation in ascites of cirrhotic patients
      detected in our hospital during the past 15years. 

PMID- 26195347
TI  - Screening and case finding for major depressive disorder using the Patient Health
      Questionnaire (PHQ-9): a meta-analysis.
AB  - OBJECTIVE: The Patient Health Questionnaire (PHQ-9) is a widely used screening
      tool for major depressive disorder (MDD), although there is debate surrounding
      its diagnostic properties. For the PHQ-9, we aimed to: 1. Establish the
      diagnostic performance at the standard cutoff point (10). 2. Compare the
      diagnostic performance at the standard cutoff point in different clinical
      settings. 3. Assess whether there is selective reporting of cutoff points other
      than 10. METHODS: We searched three databases - Embase, MEDLINE and PSYCHInfo -
      and performed a reverse citation search in Web of Science. We selected for
      inclusion studies of any design that assessed the PHQ-9 in adult populations
      against recognized gold-standard instruments for the diagnosis of either
      Diagnostic and Statistical Manual of Mental Disorders or International
      Classification of Diseases criteria for major depression. Included studies had to
      report sufficient information to calculate 2*2 contingency tables. Data
      extraction and synthesis were performed independently by two researchers. For the
      included studies, we calculated pooled sensitivity, pooled specificity, positive
      likelihood, negative likelihood ratio and diagnostic odds ratio for cutoff points
      7 to 15. RESULTS: Thirty-six studies (21,292 patients) met inclusion criteria.
      Pooled sensitivity for cutoff point 10 was 0.78 [95% confidence interval (CI),
      0.70-0.84], and pooled specificity was 0.87 (95% CI, 0.84-0.90). At this cutoff,
      the PHQ-9 is a better screener in primary care than secondary care settings. No
      conclusions could be drawn at cutoff points other than 10 due to selective
      reporting of data. CONCLUSIONS: For MDD, the PHQ-9 has acceptable diagnostic
      properties at cutoff point 10 in different settings. We recommend that future
      studies report the full range of cutoff points to allow exploration of optimal
      cutoff points in different settings.

PMID- 26195348
TI  - Describing the precursors to and management of medication nonadherence on acute
      psychiatric wards.
AB  - OBJECTIVE: This study aims to (a) describe what conflict (aggression, absconding
      etc.) and containment (de-escalation, restraining etc.) events occur before and
      after events of medication nonadherence on acute psychiatric wards and (b)
      identify which patient characteristics are associated with medication
      nonadherence. METHOD: Conflict and containment events for each shift over the
      first 2 weeks of admission were coded retrospectively from nursing records for a
      sample of 522 adult psychiatric inpatients. The frequency and order of the
      conflict and containment events were identified. Univariate logistic regression
      models were conducted to examine which patient characteristics were linked with
      medication noncompliance. RESULTS: Medication refusals were commonly preceded by
      aggression whereas demands for pro re nata (PRN) (psychotropic) were commonly
      preceded by the same patient having been given PRN medication. Refusals and
      demands for medication were commonly followed by de-escalation and given PRN
      (psychotropic) medication. Only refusal of PRN medication was commonly followed
      by forced (intramuscular) medication. Ethnicity, previous self-harm and physical
      health problems were also linked to nonadherence. CONCLUSIONS: Greater attention
      to the conflict and containment events that precede and follow medication
      nonadherence may reduce the likelihood of medication nonadherence.

PMID- 26195349
TI  - Transient signal generation in a self-assembled nanosystem fueled by ATP.
AB  - A fundamental difference exists in the way signal generation is dealt with in
      natural and synthetic systems. While nature uses the transient activation of
      signalling pathways to regulate all cellular functions, chemists rely on sensory
      devices that convert the presence of an analyte into a steady output signal. The
      development of chemical systems that bear a closer analogy to living ones (that
      is, require energy for functioning, are transient in nature and operate out-of
      equilibrium) requires a paradigm shift in the design of such systems. Here we
      report a straightforward strategy that enables transient signal generation in a
      self-assembled system and show that it can be used to mimic key features of
      natural signalling pathways, which are control over the output signal intensity
      and decay rate, the concentration-dependent activation of different signalling
      pathways and the transient downregulation of catalytic activity. Overall, the
      reported methodology provides temporal control over supramolecular processes. 

PMID- 26195350
TI  - A new gene for primary familial brain calcification: The importance of phosphate
      homeostasis.

PMID- 26195351
TI  - Two-dimensional second-order quadrupolar exchange powder spectra for nuclei with
      half-integer spins. Calculations and an experimental example using oxygen NMR.
AB  - Two-dimensional chemical exchange spectra are determined for powders containing
      half-integer quadrupolar nuclei that evolve under the second-order quadrupolar
      interaction. For simple exchange processes it is shown that the calculated
      exchange patterns depend sensitively on the jump angles, the tensor parameters,
      and the rotation axes characterizing the geometry of the underlying molecular
      motion. The inclusion of other interactions is discussed. To demonstrate the
      feasibility of the experimental method a two-dimensional second-order quadrupolar
      exchange spectrum was recorded for a clathrate hydrate using oxygen NMR.
      Simulations based on a motional model involving a six-site jump capture the
      essential features of the experimental results. 

PMID- 26195353
TI  - Total Knee Arthroplasty in Patients With a Prior Tibial Plateau Fracture: A Long
      Term Report at 15 Years.
AB  - The goal of the current study was to determine the 15-year outcomes of 62
      patients who underwent a total knee arthroplasty (TKA) after a prior tibial
      plateau fracture. Mean age at the index surgical intervention was 63 years. At
      most recent followup, there were 11 revisions. The 15-year survivorship free from
      revision for aseptic loosening was 96%. In unrevised cases, the components were
      radiographically well-fixed. There were a total of 21 complications, 90% of which
      occurred at <2 years. While patients undergoing TKA after a tibial plateau
      fracture have an increased rate of complications, the 15-year results indicate
      that subsequent survivorship is similar to that of patients undergoing TKA for
      degenerative arthritis if early complications can be avoided. 

PMID- 26195352
TI  - Hyperosmotic stress activates the expression of members of the miR-15/107 family
      and induces downregulation of anti-apoptotic genes in rat liver.
AB  - microRNAs are an abundant class of small non-coding RNAs that negatively regulate
      gene expression. Importantly, microRNA activity has been linked to the control of
      cellular stress response. In the present study, we investigated whether the
      expression of hepatic microRNAs is affected by changes in ambient osmolarity. It
      is shown that hyperosmotic exposure of perfused rat liver induces a rapid
      upregulation of miR-15a, miR-15b and miR-16, which are members of the miR-15/107
      microRNAs superfamily. It was also identified that hyperosmolarity significantly
      reduces the expression of anti-apoptotic genes including Bcl2, Ccnd1, Mcl1, Faim,
      Aatf, Bfar and Ikbkb, which are either validated or predicted targets of these
      microRNAs. Moreover, through the application of NOX and JNK inhibitors as well as
      benzylamine it is shown that the observed response is mediated by reactive oxygen
      species (ROS), suggesting that miR-15a, miR-15b and miR-16 are novel redoximiRs.
      It is concluded that the response of these three microRNAs to osmotic stress is
      ROS-mediated and that it might contribute to the development of a proapoptotic
      phenotype. 

PMID- 26195354
TI  - Regaining Native Knee Kinematics Following Joint Arthroplasty: A Novel Biomimetic
      Design with ACL and PCL Preservation.
AB  - Lack of ACL and non-anatomic articular surfaces in contemporary total knee
      implants result in kinematic abnormalities. We hypothesized that such
      abnormalities may be addressed with a biomimetic bi-cruciate retaining (BCR)
      design having anatomical articular surfaces. We used dynamic computer simulations
      to compare kinematics among the biomimetic BCR, a contemporary BCR and cruciate
      retaining implant for activities of daily living. During simulated deep knee
      bend, chair-sit and walking, the biomimetic BCR implant showed activity dependent
      kinematics similar to healthy knees in vivo. Restoring native knee geometry
      together with ACL preservation provided these kinematic improvements over
      contemporary ACL-preserving and ACL-sacrificing implants. Further clinical
      studies are required to determine if such biomimetic implants can result in more
      normal feeling knees and improve quality of life for active patients. 

PMID- 26195355
TI  - Predictors of Low Patient-Reported Outcomes Response Rates in the California
      Joint Replacement Registry.
AB  - Total joint arthroplasty registries are increasingly collecting Patient Reported
      Outcome Measures (PROM) to more directly measure clinical success after surgery.
      Obtaining these valuable, complete pre- and post-operative surveys is
      challenging. We sought to identify specific patient or provider characteristics
      that are associated with low-reporting of PROM surveys in the California Joint
      Replacement Registry (CJRR). All reported total hip and knee arthroplasties
      (n=6861) during 2011-2014 were retrospectively reviewed. PROMs were prospectively
      collected to determine factors associated with non-participation. The critical
      factor in predicting ongoing participation post-operatively was the collection of
      PROM surveys pre-operatively. Specific patient demographics (race, discharge
      disposition, occurrence of a complication) and surgeon volume were predictive of
      non-response and are potential targets for increasing reporting rates. 

PMID- 26195356
TI  - Re: Comparison of Partial Nephrectomy and Percutaneous Ablation for cT1 Renal
      Masses.

PMID- 26195357
TI  - Re: Impact of Warm versus Cold Ischemia on Renal Function following Partial
      Nephrectomy.

PMID- 26195358
TI  - Re: Salvage Surgery after Energy Ablation for Renal Masses.

PMID- 26195359
TI  - Re: Robot-Assisted Surgery for Kidney Cancer Increased Access to a Procedure that
      can Reduce Mortality and Renal Failure.

PMID- 26195361
TI  - Re: Discovery and Validation of Novel Expression Signature for Postcystectomy
      Recurrence in High-Risk Bladder Cancer.

PMID- 26195360
TI  - Re: Human Papillomavirus (HPV) Genotype- and Age-Specific Analyses of External
      Genital Lesions among Men in the HPV Infection in Men (HIM) Study.

PMID- 26195362
TI  - Re: Screening and Prostate Cancer Mortality: Results of the European Randomised
      Study of Screening for Prostate Cancer (ERSPC) at 13 Years of Follow-up.

PMID- 26195363
TI  - Re: Effect of Enzalutamide on Time to First Skeletal-Related Event, Pain, and
      Quality of Life in Men with Castration-Resistant Prostate Cancer: Results from
      the Randomised, Phase 3 AFFIRM Trial.

PMID- 26195364
TI  - Re: Improving the Specificity of Screening for Lethal Prostate Cancer Using
      Prostate-Specific Antigen and a Panel of Kallikrein Markers: A Nested Case
      Control Study.

PMID- 26195365
TI  - Re: Salvage Radical Prostatectomy for Recurrent Prostate Cancer: Verification of
      EAU Guideline Criteria.

PMID- 26195366
TI  - Re: The Impact of Obesity on the Predictive Accuracy of PSA in Men Undergoing
      Prostate Biopsy.

PMID- 26195367
TI  - Re: The Value of Magnetic Resonance Imaging in the Detection of Prostate Cancer
      in Patients with Previous Negative Biopsies and Elevated Prostate-Specific
      Antigen Levels: A Meta-Analysis.

PMID- 26195368
TI  - Re: Phenotypic Characterisation of Immune Cell Infiltrates in Testicular Germ
      Cell Neoplasia.

PMID- 26195369
TI  - Re: Effectiveness of Acupuncture on Chronic Prostatitis-Chronic Pelvic Pain
      Syndrome Category IIIB Patients: A Prospective, Randomized, Nonblinded, Clinical
      Trial.

PMID- 26195370
TI  - Re: Levofloxacin for BK Virus Prophylaxis following Kidney Transplantation: A
      Randomized Clinical Trial.

PMID- 26195371
TI  - Re: Antibiotic Prophylaxis for Urinary Tract Infections after Removal of Urinary
      Catheter: Meta-Analysis.

PMID- 26195372
TI  - Re: ABO Incompatible Renal Transplantation without Antibody Removal Using
      Conventional Immunosuppression Alone.

PMID- 26195373
TI  - Re: Oxalobacter formigenes: Opening the Door to Probiotic Therapy for the
      Treatment of Hyperoxaluria.

PMID- 26195374
TI  - Re: Biopsy Proven Medullary Sponge Kidney: Clinical Findings, Histopathology, and
      Role of Osteogenesis in Stone and Plaque Formation.

PMID- 26195375
TI  - Re: Demographics and Characterization of 10,282 Randall Plaque-Related Kidney
      Stones: A New Epidemic?

PMID- 26195376
TI  - Re: Analysis of Commercial Kidney Stone Probiotic Supplements.

PMID- 26195377
TI  - Re: Penile Fracture: Outcomes of Early Surgical Intervention.

PMID- 26195378
TI  - Re: Dorsal Plication without Degloving is Safe and Effective for Correcting
      Ventral Penile Deformities.

PMID- 26195379
TI  - Re: Sports-Related Testicular Injuries and the Use of Protective Equipment among
      Young Male Athletes.

PMID- 26195380
TI  - Re: Underlying Reasons Associated with Hospital Readmission following Surgery in
      the United States.

PMID- 26195381
TI  - Re: A Model for Predicting the Risk of De Novo Stress Urinary Incontinence in
      Women Undergoing Pelvic Organ Prolapse Surgery.

PMID- 26195382
TI  - Re: Urinary Incontinence Management Costs are Reduced following Burch or Sling
      Surgery for Stress Incontinence.

PMID- 26195383
TI  - Re: Decrease in Urinary Incontinence Management Costs in Women Enrolled in a
      Clinical Trial of Weight Loss to Treat Urinary Incontinence.

PMID- 26195384
TI  - Re: Pelvic Floor Muscle Training Added to Another Active Treatment versus the
      Same Active Treatment Alone for Urinary Incontinence in Women.

PMID- 26195385
TI  - Re: Lower Urinary Tract Symptoms in Women with Benign Joint Hypermobility
      Syndrome: A Case-Control Study.

PMID- 26195386
TI  - Re: Current Controversies Regarding Oncologic Risk Associated with Polypropylene
      Midurethral Slings.

PMID- 26195387
TI  - Re: Urodynamic Studies for Management of Urinary Incontinence in Children and
      Adults: A Short Version Cochrane Systematic Review and Meta-Analysis.

PMID- 26195388
TI  - Re: Pathophysiology of Idiopathic Overactive Bladder and the Success of
      Treatment: A Systematic Review from ICI-RS 2013.

PMID- 26195389
TI  - Re: The Impact of Tension-Free Vaginal Tape on the Urethral Closure Function:
      Mechanism of Action.

PMID- 26195390
TI  - Re: Do Continence Management Strategies Reduce Falls? A Systematic Review.

PMID- 26195391
TI  - Re: Lifetime Risk of Stress Urinary Incontinence or Pelvic Organ Prolapse
      Surgery.

PMID- 26195392
TI  - Re: Quality of Life (QoL) and Help-Seeking in Postmenopausal Women with Urinary
      Incontinence (UI): A Population Based Study.

PMID- 26195393
TI  - Re: Anticholinergic Drug Use and Negative Outcomes among the Frail Elderly
      Population Living in a Nursing Home.

PMID- 26195394
TI  - Re: Antimuscarinic Use among Individuals with Urinary Incontinence who Reside in
      Long-Term Care Facilities.

PMID- 26195395
TI  - Re: Risk of Medication-Associated Initiation of Oxybutynin in Elderly Men and
      Women.

PMID- 26195396
TI  - Re: Safety and Effectiveness of Thulium VapoEnucleation of the Prostate (ThuVEP)
      in Patients on Anticoagulant Therapy.

PMID- 26195397
TI  - Re: Temporal Trends in Anticholinergic Medication Prescription in Older People:
      Repeated Cross-Sectional Analysis of Population Prescribing Data.

PMID- 26195398
TI  - Re: 180-W XPS GreenLight Laser Vaporisation versus Transurethral Resection of the
      Prostate for the Treatment of Benign Prostatic Obstruction: 6-Month Safety and
      Efficacy Results of a European Multicentre Randomised Trial-the GOLIATH Study.

PMID- 26195399
TI  - Re: Morbidity and Mortality after Benign Prostatic Hyperplasia Surgery: Data from
      the American College of Surgeons National Surgical Quality Improvement Program.

PMID- 26195400
TI  - Re: Factors Associated with Continuing Medical Therapy after Transurethral
      Resection of Prostate.

PMID- 26195401
TI  - Re: Outcomes in Kidney Transplant Recipients from Older Living Donors.

PMID- 26195402
TI  - Re: Frailty and Mortality in Kidney Transplant Recipients.

PMID- 26195403
TI  - Re: Robotic Trans-Abdominal Transplant Nephrectomy for a Failed Renal Allograft.

PMID- 26195404
TI  - Re: Increased Risk of Erectile Dysfunction among Patients with Sleep Disorders: A
      Nationwide Population-Based Cohort Study.

PMID- 26195405
TI  - Re: Men's Contraceptive Practices in France: Evidence of Male Involvement in
      Family Planning.

PMID- 26195406
TI  - Re: Correlation between Premature Ejaculation and Female Vaginal Penetration
      Difficulties.

PMID- 26195407
TI  - Re: A Home-Based Walking Program Improves Erectile Dysfunction in Men with an
      Acute Myocardial Infarction.

PMID- 26195408
TI  - Re: Efficacy of Once-Daily Administration of Udenafil for 24 Weeks on Erectile
      Dysfunction: Results from a Randomized Multicenter Placebo-Controlled Clinical
      Trial.

PMID- 26195409
TI  - Re: The Impact of Multimorbidity on Sexual Function in Middle-Aged and Older
      Women: Beyond the Single Disease Perspective.

PMID- 26195410
TI  - Re: Sexual Function in the Late Postmenopause: A Decade of Follow-up in a
      Population-Based Cohort of Australian Women.

PMID- 26195411
TI  - Re: The Relationship between Health-Related Quality of Life, Obesity and
      Testosterone Levels in Older Men.

PMID- 26195412
TI  - Re: Low Testosterone Levels, Depressive Symptoms, and Falls in Older Men: A Cross
      Sectional Study.

PMID- 26195413
TI  - Re: Lower Urinary Tract Symptoms Improve with Testosterone Replacement Therapy in
      Men with Late-Onset Hypogonadism: 5-Year Prospective, Observational and
      Longitudinal Registry Study.

PMID- 26195414
TI  - Re: Relationship between Semen Production and Medical Comorbidity.

PMID- 26195415
TI  - Re: Dietary Fatty Acid Intakes and Asthenozoospermia: A Case-Control Study.

PMID- 26195416
TI  - Re: Cholesterol-Enriched Diet Disrupts the Blood-Testis Barrier in Rabbits.

PMID- 26195417
TI  - Re: Hepatitis B Virus Infection and the Risk of Male Infertility: A Population
      Based Analysis.

PMID- 26195418
TI  - Re: Vasectomy Reversal Outcomes in Men Previously on Testosterone Supplementation
      Therapy.

PMID- 26195419
TI  - Re: Disparities in Stage at Diagnosis, Treatment, and Survival in Nonelderly
      Adult Patients with Cancer According to Insurance Status.

PMID- 26195420
TI  - Re: National Health Expenditure Projections, 2013-23: Faster Growth Expected with
      Expanded Coverage and Improving Economy.

PMID- 26195421
TI  - Re: Making Cuts to Medicare: The Views of Patients, Physicians, and the Public.

PMID- 26195422
TI  - Re: A Model of Disruptive Surgeon Behavior in the Perioperative Environment.

PMID- 26195423
TI  - Re: Comparison between Laparoscopic and Open Radical Nephrectomy for the
      Treatment of Primary Renal Tumors in Children: Single-Center Experience over a 5
      Year Period.

PMID- 26195424
TI  - Re: British Association of Paediatric Urologists Consensus Statement on the
      Management of the Primary Obstructive Megaureter.

PMID- 26195425
TI  - Re: Refluxing Ureteral Reimplantation: A Logical Method for Managing Neonatal UVJ
      Obstruction.

PMID- 26195426
TI  - Re: Staphylococcus aureus Urinary Tract Infections in Children are Associated
      with Urinary Tract Abnormalities and Vesico-Ureteral Reflux.

PMID- 26195427
TI  - Re: Sall1 Maintains Nephron Progenitors and Nascent Nephrons by Acting as Both an
      Activator and a Repressor.

PMID- 26195428
TI  - Re: Expression and Localization of a UT-B Urea Transporter in the Human Bladder.

PMID- 26195429
TI  - Re: Circulating Biomarkers of One-Carbon Metabolism in Relation to Renal Cell
      Carcinoma Incidence and Survival.

PMID- 26195430
TI  - Re: Artificial Hand for Minimally Invasive Surgery: Design and Testing of Initial
      Prototype.

PMID- 26195431
TI  - Monitoring of TiO2-catalytic UV-LED photo-oxidation of cyanide contained in mine
      wastewater and leachate.
AB  - A photo-oxidation process using UV-LEDs and TiO2 was studied for removal of
      cyanide contained in mine wastewater and leachates. This study focused on
      monitoring of a TiO2-catalyzed LED photo-oxidation process, particularly
      emphasizing the effects of TiO2 form and light source on the efficiency of
      cyanide removal. The generation of hydroxyl radicals was also examined during the
      process to evaluate the mechanism of the photo-catalytic process. The apparent
      removal efficiency of UV-LEDs was lower than that achieved using a UV-lamp, but
      cyanide removal in response to irradiation as well as consumption of electrical
      energy was observed to be higher for UV-LEDs than for UV-lamps. The Degussa P25
      TiO2 showed the highest performance of the TiO2 photo-catalysts tested. The
      experimental results indicate that hydroxyl radicals oxidize cyanide to OCN(-),
      NO2(-), NO3(-), HCO3(-), and CO3(2-), which have lower toxicity than cyanide. In
      addition, the overall efficacy of the process appeared to be significantly
      affected by diverse operational parameters, such as the mixing ratio of anatase
      and rutile, the type of gas injected, and the number of UV-LEDs used. 

PMID- 26195432
TI  - Methylmercury in colostrum and milk of Japanese mothers.

PMID- 26195433
TI  - Insights into IL-23 biology: From structure to function.
AB  - Interleukin (IL-)23 is a central cytokine controlling TH17 development.
      Overshooting IL-23 signaling contribute to autoimmune diseases. Moreover, GWAS
      studies have identified several SNPs within the IL-23 receptor, which are
      associated with autoimmune diseases. IL-23 is a member of the IL-12-type cytokine
      family and consists of IL-23p19 and p40. Within the IL-12 family, IL-12 and IL-23
      share the p40 cytokine subunit and the IL-12Rbeta1 as one chain of the receptor
      complex. For signaling, IL-23 triggers heterodimerization of IL-12Rbeta1 and the
      IL-23R. Subsequently, signal transduction pathways including JAK/STAT, MAPK and
      PI3K are activated. Most studies have investigated the biological relevance of IL
      23 in the development of TH17 cells and autoimmunity, whereas less is known about
      the molecular context of IL-23 biology. Therefore, we focused on IL-23 receptor
      complex assembly, signal transduction and functional relevance of IL-23R SNPs in
      the context of IL-23-inhibitory principles. 

PMID- 26195434
TI  - The biology of interleukin-27 reveals unique pro- and anti-inflammatory functions
      in immunity.
AB  - Interleukin (IL)-27 is a multifaceted heterodimeric cytokine with pronounced pro-
      and anti-inflammatory as well as immunoregulatory functions. It consists of the
      two subunits p28/IL-30 and Epstein Bar virus-induced protein 3 (EBI3). EBI3
      functions as a soluble alpha-receptor, and IL-27 can therefore directly activate
      its target cells through a heterodimer of glycoprotein 130 (gp130) and WSX-1.
      Being a heterodimeric cytokine that signals through gp130, IL-27 is either
      grouped into the IL-6 or the IL-12 family of cytokines. Originally identified as
      an IL-12-like cytokine that induces proliferation of CD4+ T cells and production
      of IFN-gamma more than ten years ago, subsequent research revealed a much broader
      role of IL-27 in inflammation, cancer development and regulation and
      differentiation of immune cells. In this review, we summarize the current
      biochemical and molecular knowledge about the signal transduction of IL-27. Based
      on this, we highlight functional overlaps and plasticity with other cytokines and
      cytokine receptors of the IL-6/IL-12 superfamily, and describe the important role
      of IL-27 with regard to the differentiation of T cells, infections and cancer
      development. We further discuss IL-27 as a therapeutic target and how specific
      blockade of this cytokine could be achieved. 

PMID- 26195435
TI  - Brentuximab Vedotin in CD30-Positive Lymphomas: A SIE, SIES, and GITMO Position
      Paper.
AB  - Brentuximab vedotin (BV) is approved for the treatment of patients with relapsed
      or refractory CD30-positive Hodgkin lymphoma, and relapsed or refractory systemic
      anaplastic large-cell lymphoma. Several uncertainties remain regarding the
      optimal use of the drug in its approved indications as well as outside them. This
      article reports recommendations on the use of BV issued during a consensus
      project, sponsored by the Italian Society of Hematology (SIE) and its affiliate
      societies, Societa Italiana di Ematologia Sperimentale (SIES) and Gruppo Italiano
      Trapianto di Midollo Osseo (GITMO). Scientific evidence on BV was evaluated by a
      panel of experts, and consensus was developed by group discussion for key
      questions selected according to the clinical relevance. The following key issues
      were addressed: testing CD30 positivity to assess eligibility to BV; assessing
      practice indications of BV in Hodgkin lymphoma and systemic anaplastic large-cell
      lymphoma; providing pretreatment evaluation of patients candidates to BV;
      monitoring the response to BV; managing patients treated with BV; and assessing
      the role of BV in other CD30-positive lymphomas.

PMID- 26195436
TI  - Postoperative CMF Does Not Ameliorate Poor Outcomes in Women With Residual
      Invasive Breast Cancer After Neoadjuvant Epirubicin/Docetaxel Chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NACT) is an accepted treatment approach in
      early-stage breast cancer. In contrast, the potential role of postneoadjuvant
      chemotherapy after taxane-containing NACT remains unclear. The aim of this study
      was to evaluate postneoadjuvant chemotherapy and further prognostic factors that
      predict outcome in women without pathologic complete remission (pCR). PATIENTS
      AND METHODS: A total of 377 patients with breast cancer who received preoperative
      chemotherapy were included in this retrospective study. Patients without standard
      NACT (6 cycles of epirubicin with docetaxel) or primary metastatic breast cancer
      and locally advanced, inoperable cancer were excluded from further analysis (n =
      186). This resulted in a study population of 191 women (30 [15.7%] with pCR; 161
      [84.3%] without pCR). Major outcome parameters were event-free survival (EFS) and
      overall survival (OS). The following parameters were tested for their prognostic
      role: postneoadjuvant chemotherapy, patient age, breast cancer subtype
      (luminal/HER2-negative tumors, HER2-positive tumors, and triple-negative tumors),
      histological grade, pCR, residual lymph node invasion, and residual invasive
      tumor size. RESULTS: At a median follow-up of 54 months, 51 disease relapses
      (26.7%) and 21 deaths (11%) were observed. In a comparison of patients with pCR
      with those without, no significant differences in EFS or OS were observed.
      Postneoadjuvant chemotherapy was significantly associated with shorter OS in
      patients without pCR. CONCLUSION: In this population, which included a high
      percentage of patients with luminal cancers, pCR did not predict for improved OS.
      Postneoadjuvant chemotherapy showed no discernible benefit even in subgroups with
      aggressive tumor biology or significant remaining tumor burden. The use of such
      treatment should therefore be discouraged outside of clinical trials.

PMID- 26195437
TI  - Epigenetic Inactivation of BRCA1 Through Promoter Hypermethylation and Its
      Clinical Importance in Triple-Negative Breast Cancer.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) has many similarities with basal
      like breast cancer. Additionally, TNBCs are associated with Breast cancer
      susceptibility gene I (BRCA1) functional loss, which leads to impaired homologous
      recombination-mediated DNA repair. Although somatic mutations in BRCA1 rarely
      occur in sporadic breast cancer, lower than normal rates of expression of BRCA1
      is reported to be an important factor that contributes to tumorigenesis in
      sporadic tumors. The epigenetic inactivation of BRCA1 expression might thus play
      an important role in sporadic breast cancer cases. PATIENTS AND METHODS: Breast
      cancer specimens were obtained from 69 TNBC and 161 non-TNBC patients who
      underwent surgery without neoadjuvant systemic therapy. BRCA1 promoter
      methylation status was investigated using combined bisulfite and restriction
      analysis. BRCA1 mRNA expression was evaluated using quantitative reverse
      transcriptase polymerase chain reaction and BRCA1 protein expression was assessed
      using immunohistochemistry. RESULTS: BRCA1 promoter methylation was found in 11
      tumors and all of these were in TNBC cases (P < .0001). BRCA1 promoter
      methylation was significantly associated with lymphovessel invasion (P = .02),
      high nuclear grade (P = .05), low BRCA1 mRNA expression (P < .0001), and loss of
      BRCA1 protein expression (P = .0015). BRCA1 promoter methylation was
      significantly associated with shorter overall survival (P = .038). CONCLUSION:
      BRCA1 promotor methylation was found only in TNBC cases and the methylated cases
      account for 16% of TNBC. BRCA1 promoter methylation was significantly associated
      with reduced BRCA1 expression, aggressive phenotype, and poor prognosis. BRCA1
      promoter methylation is an important mechanism that leads to functional loss of
      BRCA1.

PMID- 26195438
TI  - Multiple reasonably tolerated percutaneous coronary interventions in a patient
      with iodide mumps.

PMID- 26195439
TI  - Non-adherence to subcutaneous allergen immunotherapy: inadequate health insurance
      coverage is the leading cause.
AB  - BACKGROUND: To sustain the long-lasting beneficial effects of subcutaneous
      allergen immunotherapy, the recommended duration of treatment is 3 to 5 years.
      Nevertheless, many patients discontinue allergy injections prematurely and
      therefore might not appreciate the full therapeutic benefit. OBJECTIVE: To
      examine factors leading to premature discontinuation of subcutaneous allergen
      immunotherapy (cessation before completion of the recommended duration). METHODS:
      Patients who discontinued immunotherapy before the completion of the prescribed
      duration and received their final injection from January 2008 through September
      2013 were contacted to identify the reason for stopping the allergy injections.
      Phase of treatment (escalation or maintenance) was used to measure the duration
      of treatment at the time of cessation and patients were grouped accordingly.
      RESULTS: The study population consisted of 555 patients with allergic rhinitis
      and/or asthma who terminated immunotherapy prematurely. Two hundred thirteen
      (38%) were men and 342 (62%) were women. The following reasons were cited by
      patients for non-adherence to immunotherapy: requirement of copayment for allergy
      injections and/or payment for allergen extract by their health insurer (40%);
      inconvenience of travel (15%); change of residence (8%); concurrent health
      problems (5%); patient-perceived ineffectiveness (4%); patient-perceived lack of
      need to continue immunotherapy (2%); adverse effects from injection (local
      reaction 1%; systemic allergic reaction 0.5%); and trial of alternative medicine
      (0.1%). The remaining 24.4% did not provide a reason for discontinuation.
      CONCLUSION: Of the various factors, inadequate reimbursement for allergen extract
      and allergy injections by health insurers is the most common reason cited for non
      adherence to subcutaneous allergen immunotherapy.

PMID- 26195440
TI  - Boletus dermatitis: a new variant of flagellate erythema.

PMID- 26195441
TI  - Relation of lung function and current inhalant allergen-specific immunoglobulin E
      concentrations in adolescents (GINIplus cohort).
AB  - BACKGROUND: The prevalence of allergen sensitization reaches up to 46.6% in 14-
      to 17-year-old German adolescents. Polysensitization is strongly associated with
      a higher risk of allergic rhinitis or asthma. Whether or how sensitization also
      is related to lung function remains uncertain. OBJECTIVE: To assess whether
      sensitization to common inhalant allergens is associated with lung function in
      adolescents after stratification by allergic respiratory disease. METHODS: In
      total, 1,719 15-year-old participants of the German Infant Study on the Influence
      of Nutrition Intervention plus Air Pollution and Genetics on Allergy Development
      (GINIplus) birth cohort provided valid spirometric indices, including forced
      expiratory volume in 1 second, forced vital capacity (FVC), forced expiratory
      flow rate at 25% to 75% of the FVC, and specific immunoglobulin E (IgE) screening
      test to 8 inhalant allergens (ImmunoCAP). Complete information on allergic
      rhinitis and asthma status was available for 1,128 subjects. Associations between
      lung function parameters and sensitization, classified into 4 groups (no
      sensitization to polysensitization) were analyzed using adjusted linear
      regression models. RESULTS: Among participants, 21.1% (n = 347) had allergic
      rhinitis, 10.1% (n = 119) had asthma, and 46.4% (n = 798) had a positive
      screening test to inhalant allergens. Prevalences were consistently higher in
      boys. The percentage of subjects with rhinitis or asthma increased from 5.8% in
      non-sensitized subjects (n = 620) to 69.4% in polysensitized subjects (n = 144).
      Sensitization was not associated with any spirometric parameter considered in
      subjects with allergic rhinitis, asthma, or neither disease. CONCLUSION: Although
      allergen-specific IgE concentrations can contribute to the identification of
      subjects at higher risk for allergic rhinitis and asthma, sensitization to
      inhalant allergens is not related to impaired spirometric lung parameters within
      the different allergic respiratory disease subgroups.

PMID- 26195442
TI  - US Medicare, Medicaid, and nurse practitioners all turn 50.

PMID- 26195443
TI  - Modelling knee flexion effects on joint power absorption and adduction moment.
AB  - BACKGROUND: Knee osteoarthritis is commonly associated with ageing and long-term
      walking. In this study the effects of flexing motions on knee kinetics during
      stance were simulated. Extended knees do not facilitate efficient loading. It was
      therefore, hypothesised that knee flexion would promote power absorption and
      negative work, while possibly reducing knee adduction moment. METHODS: Three
      dimensional (3D) position and ground reaction forces were collected from the
      right lower limb stance phase of one healthy young male subject. 3D position was
      sampled at 100 Hz using three Optotrak Certus (Northern Digital Inc.) motion
      analysis camera units, set up around an eight metre walkway. Force plates (AMTI)
      recorded ground reaction forces for inverse dynamics calculations. The Visual 3D
      (C-motion) 'Landmark' function was used to change knee joint positions to
      simulate three knee flexion angles during static standing. Effects of the flexion
      angles on joint kinetics during the stance phase were then modelled. RESULTS: The
      static modelling showed that each 2.7 degrees  increment in knee flexion angle
      produced 2.74 degrees -2.76 degrees  increments in knee flexion during stance.
      Increased peak extension moment was 6.61 Nm per 2.7 degrees  of increased knee
      flexion. Knee flexion enhanced peak power absorption and negative work, while
      decreasing adduction moment. CONCLUSIONS: Excessive knee extension impairs
      quadriceps' power absorption and reduces eccentric muscle activity, potentially
      leading to knee osteoarthritis. A more flexed knee is accompanied by reduced
      adduction moment. Research is required to determine the optimum knee flexion to
      prevent further damage to knee-joint structures affected by osteoarthritis.

PMID- 26195445
TI  - Bladder cancer: Cancer cell sampling and storage-new filtration device aids
      collection from urine.

PMID- 26195444
TI  - New intraprostatic injectables and prostatic urethral lift for male LUTS.
AB  - Treatment modalities for male lower urinary tract symptoms (LUTS) comprise a
      broad spectrum of medical and surgical options. Interest is growing in minimally
      invasive treatment options, which should ideally be performed in an outpatient
      setting and have a short recovery time, durable efficacy and a good safety
      profile. The preservation of all aspects of sexual function, including antegrade
      ejaculation, seems to be increasingly important for patients. Initial
      experimental data on new minimally invasive procedures-such as the intraprostatic
      injection of novel agents including botulinum neurotoxin A (BoNT-A), NX-1207 and
      PRX302-were promising, but clinical trials have not confirmed the findings.
      Trials of the mechanical prostatic urethral lift device-Urolift((r)) (Neotract,
      Inc., USA)-have been positive, but further long-term results are needed to
      confirm its beneficial effects. 

PMID- 26195448
TI  - Urinary incontinence: Pirt inhibits overactive bladder.

PMID- 26195451
TI  - Incidence of port-site hernia following robotic-assisted sacrocolpopexy.

PMID- 26195452
TI  - The burden of attending a pediatric surgical clinic and family preferences toward
      telemedicine.
AB  - BACKGROUND/PURPOSE: Indirect expenses for accessing health care may place
      significant fiscal strain on Canadian families. Telemedicine alternatives, using
      email, telephone, and video conferencing, can mitigate such financial burdens by
      reducing travel and related costs. Our objectives were to assess costs that
      families incur visiting an outpatient pediatric surgical clinic, and family
      attitudes toward telemedicine alternatives. METHODS: A survey was offered pre
      consult to all families who attended pediatric urology and general surgery
      outpatient clinics over a three-month period. RESULTS: A total of 1032 of 1574
      families screened participated (66.0%). Less than half (18.5%) of participants
      traveled over 200 km, and 32.9% spent over 4 hours in transit, round-trip. The
      proportion of participants who spent over $50 on travel and ancillary expenses
      was 33.0%. In 74.0% of families, 1 or more adults missed work. The proportion of
      families who perceived costs as somewhat high or high was 29.1%. Perceived cost
      was positively correlated to distance traveled, money spent, and missed work
      (p<0.01). Most were comfortable with medical communication using technology; and
      34.3%-42.7% would avoid an in-person clinic visit utilizing email, telephone, and
      video conferencing. Higher perceived cost (p<0.001) and distance traveled
      (p<0.01) were only weakly associated with greater willingness to substitute a
      clinic visit with video conferencing. CONCLUSIONS: Many families face high costs
      related to routine outpatient clinical visits, and there is a substantial
      willingness by them to access telemedicine alternatives, rather than the
      traditional face-to-face clinical visit.

PMID- 26195453
TI  - A High-Throughput Assay for Rho Guanine Nucleotide Exchange Factors Based on the
      Transcreener GDP Assay.
AB  - Ras homologous (Rho) family GTPases act as molecular switches controlling cell
      growth, movement, and gene expression by cycling between inactive guanosine
      diphosphate (GDP)- and active guanosine triphosphate (GTP)-bound conformations.
      Guanine nucleotide exchange factors (GEFs) positively regulate Rho GTPases by
      accelerating GDP dissociation to allow formation of the active, GTP-bound
      complex. Rho proteins are directly involved in cancer pathways, especially cell
      migration and invasion, and inhibiting GEFs holds potential as a therapeutic
      strategy to diminish Rho-dependent oncogenesis. Methods for measuring GEF
      activity suitable for high-throughput screening (HTS) are limited. We developed a
      simple, generic biochemical assay method for measuring GEF activity based on the
      fact that GDP dissociation is generally the rate-limiting step in the Rho GTPase
      catalytic cycle, and thus addition of a GEF causes an increase in steady-state
      GTPase activity. We used the Transcreener GDP Assay, which relies on selective
      immunodetection of GDP, to measure the GEF-dependent stimulation of steady-state
      GTP hydrolysis by small GTPases using Dbs (Dbl's big sister) as a GEF for Cdc42,
      RhoA, and RhoB. The assay is well suited for HTS, with a homogenous format and
      far red fluorescence polarization (FP) readout, and it should be broadly
      applicable to diverse Rho GEF/GTPase pairs. 

PMID- 26195454
TI  - Doctors take to Twitter to refute Hunt's claim that NHS has weekday working
      culture.

PMID- 26195455
TI  - "Improved" But Not Necessarily Safe: An Assessment of Fecal Contamination of
      Household Drinking Water in Rural Peru.
AB  - The indicator used to measure progress toward the Millennium Development Goal
      (MDG) for water is access to an improved water supply. However, improved supplies
      are frequently fecally contaminated in developing countries. We examined factors
      associated with Escherichia coli contamination of improved water supplies in
      rural Pisco province, Peru. A random sample of 207 households with at least one
      child less than 5 years old was surveyed, and water samples from the source and
      storage container were tested for E. coli contamination. Although over 90% of
      households used an improved water source, 47% of source and 43% of stored water
      samples were contaminated with E. coli. Pouring or using a spigot to obtain water
      from the storage container instead of dipping a hand or object was associated
      with decreased risk of contamination of stored water (adjusted prevalence ratio
      [aPR] = 0.58, 95% confidence interval [CI] = 0.42, 0.80). Container cleanliness
      (aPR = 0.67, 95% CI = 0.45, 1.00) and correct handwashing technique (aPR = 0.62,
      95% CI = 0.42, 0.90) were also associated with decreased contamination risk.
      These findings highlighted the limitations of improved water supplies as an
      indicator of safe water access. To ensure water safety in the home, household
      water treatment and improved hygiene, water handling, and storage practices
      should be promoted. 

PMID- 26195456
TI  - Helicobacter pylori Infection in Rural and Urban Dyspeptic Patients from
      Venezuela.
AB  - The goal of this work was to assess the Helicobacter pylori prevalence in a rural
      mestizo population and compare it to an urban population from Venezuela. The
      study was performed in gastric juice samples of 71 dyspeptic patients from
      Caracas (urban) and 39 from Tucupita (rural), in the Orinoco Delta region.
      Helicobacter pylori was detected by amplification of 16S rRNA, glmM, and ureA
      genes in 55.0% patients from urban and 87.2% from rural populations. cagA was
      found positive in 51% and 62% urban and rural patients, respectively. Non-H.
      pylori Helicobacter species were not detected in the urban population, but was
      found in 7.7% of patients in the rural study site. Frequency values of the 16S
      rRNA, glmM, and ureA genes were higher in the rural population. The odds ratio
      for each gene was 15.18 for 16S rRNA, 2.34 for glmM, 2.89 for ureA, and 1.53
      cagA, showing significant differences except for cagA when gene frequency was
      compared in both populations. These results demonstrate a higher frequency of H.
      pylori and gastric non-H. pylori Helicobacter infection in a rural mestizo
      population with low hygienic standards as compared with city dwellers,
      representing a potential risk for the development of gastroduodenal diseases. 

PMID- 26195457
TI  - Potential Contribution of Iron Deficiency and Multiple Factors to Anemia Among 6-
      to 72-Month-Old Children in the Kokang Area of Myanmar.
AB  - The prevalence of anemia among children in Myanmar has been reported to be among
      the highest in the world. This study was conducted to determine 1) the prevalence
      of anemia in preschool children and 2) risk factors associated with anemia. A
      total of 138 children aged from 6 to 72 months were recruited through cluster
      sampling from six villages in Kokang. Hemoglobin (Hb) concentration, blood trace
      elements, and anthropometric indicators were measured. Feces samples were
      collected to examine for the presence of ascarid eggs. The overall prevalence of
      anemia in children was 61.6%, including 10.9% with severe anemia. Meanwhile, high
      prevalence of stunting (40.0%), underweight (22.4%), wasting (6.3%), and small
      head circumference (6.7%) was found. Children with anemia were more prone to
      stunting. Children with severe anemia and moderate anemia had significantly lower
      blood iron and zinc levels than children without anemia (P < 0.001 and P =
      0.007). The prevalence of ascarid infection was 64.9%; however, it was not
      associated with anemia. Drinking spring water was positively associated with
      anemia (odds ratio [OR] = 6.368). This study demonstrated that anemia is an
      important public health problem among children from the Kokang area. Iron
      deficiency and drinking spring water may be the important causes of anemia among
      children. 

PMID- 26195458
TI  - Hyperreactive Malarial Splenomegaly Syndrome--Can the Diagnostic Criteria Be
      Improved?
AB  - Hyperreactive Malarial Splenomegaly Syndrome (HMSS) was described and defined
      before sensitive tests for malaria were available. We present a series of seven
      individuals who were referred to our clinics with possible HMSS. Chronic malaria
      was demonstrated in those successfully treated but not in those who failed to
      respond to therapy. This observation suggests that the newer molecular malaria
      assays have a role to play in the identification of individuals who are likely to
      respond to treatment for HMSS in non-endemic regions. 

PMID- 26195459
TI  - The Impact of Ventilation and Early Diagnosis on Tuberculosis Transmission in
      Brazilian Prisons.
AB  - Prisoners have among the highest incidence of tuberculosis (TB) globally.
      However, the contribution of the prison environment on transmission is not well
      understood and structural characteristics have received little attention as
      effective epidemiological interventions in TB control. We evaluated architectural
      characteristics and estimated ventilation rates in 141 cells in three prisons in
      central west Brazil using steady-state exhaled carbon dioxide (CO2) levels. We
      used a modified Wells-Riley equation to estimate the probability of infection for
      inmates sharing a cell with an infectious case and projected the impact of
      interventions, including early diagnosis and improved ventilation. Overall,
      prison cells were densely populated (mean 2.1 m(2) per occupant) and poorly
      ventilated, with only three cells meeting World Health Organization (WHO)
      standards for per-person ventilation (60 L/s) applied in infection control
      settings. In the absence of interventions, projected mean risk of infection was
      78.0% during a 6-month period. Decreasing time-to-diagnosis by 25% reduced
      transmission risk by 8.3%. Improving ventilation to WHO standards decreased
      transmission by 38.2%, whereas optimizing cross-ventilation reduced transmission
      by 64.4%. Prison environments promote high infection risk over short-time
      intervals. In this context, enhanced diagnostics have a limited impact on
      reducing transmission. Improving natural ventilation may be required to
      effectively control TB in prisons. 

PMID- 26195460
TI  - Long-Lasting Permethrin-Impregnated Clothing Protects Against Mosquito Bites in
      Outdoor Workers.
AB  - Outdoor exposure to mosquitoes is a risk factor for many diseases, including
      malaria and dengue. We have previously shown that long-lasting permethrin
      impregnated clothing protects against tick and chigger bites in a double-blind
      randomized controlled trial in North Carolina outdoor workers. Here, we evaluated
      whether this clothing is protective against mosquito bites by measuring changes
      in antibody titers to mosquito salivary gland extracts. On average, there was a
      10-fold increase in titer during the spring and summer when mosquito exposure was
      likely to be the highest. During the first year of the study, the increase in
      titer in subjects wearing treated uniforms was 2- to 2.5-fold lower than that of
      control subjects. This finding suggests that long-lasting permethrin-impregnated
      clothing provided protection against mosquito bites. 

PMID- 26195461
TI  - Determinants of Utilization of Health Extension Workers in the Context of Scale
      Up of Integrated Community Case Management of Childhood Illnesses in Ethiopia.
AB  - Ethiopia has invested significant resources in integrated community case
      management (iCCM) of childhood illness. In Oromia Region, iCCM scale-up was
      phased in, allowing for comparisons between districts providing iCCM and routine
      services. We assessed the determinants of utilization of health extension workers
      (HEWs) delivering iCCM services at rural health posts by caregivers of sick,
      under-five children in a cross-sectional survey. We found low utilization of HEWs
      with only 9.3% of caregivers of a child sick with diarrhea, fever, and/or
      pneumonia in the previous 2 weeks taking their child to HEWs in both iCCM and
      routine areas. There was a higher likelihood of utilization of HEWs in iCCM areas
      (OR: 1.44; 95% CI: 0.97-2.12; P = 0.07), but this effect disappeared after
      accounting for confounders. In iCCM areas, maternal education, illness type, and
      distance were associated with utilization. Perceptions of illness severity and
      service quality were the primary reasons given for not utilizing the health post.
      Our findings suggest that though iCCM is reaching some vulnerable populations,
      there remain significant barriers to use of HEWs delivering iCCM services.
      Efforts for demand generation and minimization of remaining barriers are urgently
      needed for the sustained success of the iCCM strategy in Ethiopia. 

PMID- 26195462
TI  - Detection of Chikungunya Virus in Nepal.
AB  - Chikungunya virus (CHIKV) is an emerging alphaviral disease and a public health
      problem in South Asia including Nepal in recent years. In this study, sera were
      collected from patients presenting with fever, headache, muscular pain, fatigue,
      and joint pain of both upper and lower extremities. A total of 169 serum samples
      were tested for CHIKV and dengue virus (DENV) by using Immunoglobulin M (IgM) and
      Immunoglobulin G (IgG) antibody using enzyme-linked immunosorbent assay (ELISA)
      method during August to November 2013. Results showed that 3.6% and 27.8% samples
      were positive for CHIKV and DENV IgM positive, respectively. Similarly, results
      of IgG showed 3.0% samples were positive for CHIKV IgG and 29.0% were for DENV
      IgG positive. Further, a 50% focal reduction neutralization test (FRNT50) was
      performed to confirm the presence of CHIKV, which demonstrated that 8.9% of CHIKV
      IgM and/or IgG ELISA positive possessed neutralizing anti-CHIK antibodies. To our
      knowledge, this is the first report in which the presence of CHIKV is confirmed
      in Nepalese patients by FRNT50. Basic scientists and clinicians need to consider
      CHIKV as a differential diagnosis in febrile Nepalese patients, and policy makers
      should consider appropriate surveillance and actions for control strategies. 

PMID- 26195463
TI  - Strongyloides stercoralis Hyperinfection Syndrome Presenting as Severe, Recurrent
      Gastrointestinal Bleeding, Leading to a Diagnosis of Cushing Disease.
AB  - A 50-year-old male immigrant from Ethiopia presented for consultation after 3
      years of hematochezia/melena requiring > 25 units of blood transfusions. Physical
      examination revealed severe proximal muscle wasting and weakness, central
      obesity, proptosis, and abdominal striae, accompanied by eosinophilia, elevated
      hemoglobin A1c, elevated 24-hour urinary cortisol, lack of suppression of 8 am
      cortisol levels by 1 mg dexamethasone, and inappropriately elevated random
      adrenocorticotropic hormone (ACTH) level. Histopathological examination of
      gastrointestinal biopsies showed large numbers of Strongyloides stercoralis,
      indicating Strongyloides hyperinfection. Treatment with 2 days of ivermectin led
      to resolution of gastrointestinal bleeding. This syndrome was due to chronic
      immunosuppression from a pituitary ACTH (corticotroph) microadenoma, of which
      resection led to gradual normalization of urine cortisol, improved glycemic
      control, resolution of eosinophilia, and no recurrence of infection. 

PMID- 26195464
TI  - Payment for Health Care and Perception of the National Health Insurance Scheme in
      a Rural Area in Southwest Nigeria.
AB  - Health insurance coverage of the informal sector is a challenge in Nigeria. This
      study assessed the methods of payment for health care and awareness about the
      National Health Insurance Scheme (NHIS) among members of selected households in a
      rural area in the southwest of Nigeria. Using a multistage sampling technique, a
      semi-structured, pretested interviewer-administered questionnaire was used to
      collect data from 345 households. The majority of the people still pay for health
      care by out-of-pocket (OOP) method. Awareness about the NHIS in Nigeria was poor,
      but attitude to it was encouraging; and from the responses obtained, the people
      implied that they were willing to enroll in the scheme if the opportunity is
      offered. However, lack of trust in government social policies, religious belief,
      and poverty were some of the factors that might impede the implementation and
      expansion of the NHIS in the informal sector. Stakeholders should promote
      socioculturally appropriate awareness program about the NHIS and its benefits.
      Factors that might present challenges to the scheme should be adequately
      addressed by the government and other stakeholders associated with prepayment
      schemes in Nigeria. 

PMID- 26195465
TI  - Shigellosis in Subjects with Traveler's Diarrhea Versus Domestically Acquired
      Diarrhea: Implications for Antimicrobial Therapy and Human Immunodeficiency Virus
      Surveillance.
AB  - An increase of sexually transmitted shigellosis is currently being reported in
      developed countries. In addition, travel-related shigellosis can introduce
      resistant strains that could be disseminated within this new scenario.
      Epidemiological features and antimicrobial susceptibility of shigellosis
      depending on where infection was acquired were investigated. From 2008 to 2013,
      subjects with shigellosis were studied. Patients were classified according to
      acquisition of Shigella as traveler's diarrhea (TD) or domestically acquired
      diarrhea (DAD). Ninety cases of shigellosis were identified: 76 corresponding to
      the TD group and 14 to the DAD group. In the DAD group, most of patients were
      human immunodeficiency virus (HIV)-positive men who have sex with men (MSM),
      being shigellosis associated to male sex (P = 0.007) and HIV infection (P <
      0.0001). S. sonnei (47.8%) and S. flexneri (42.2%) were the predominant species.
      The highest resistance was detected for trimethoprim/sulfamethoxazole (SXT)
      (81.8%), followed by ampicillin (AMP) (37.8%) and ciprofloxacin (CIP) (23.3%).
      Resistant Shigella strains were more frequent in subjects with TD than those with
      DAD, although only for CIP the difference was significant (P = 0.034). Continuous
      monitoring of patients with shigellosis is necessary to control the spread of
      resistant Shigella strains and for effective therapy. Men with shigellosis who
      have not traveled to an endemic area should be screened for HIV infection. 

PMID- 26195466
TI  - Impact of Global Health Research Training on Career Trajectories: The Fogarty
      International Clinical Research Scholars and Fellows Program.
AB  - From 2004 to 2012, the Fogarty International Clinical Research Scholars/Fellows
      Program (FICRS-F) provided 1-year research training opportunities for U.S. and
      international doctoral "Scholars" and postdoctoral "Fellows" at low- and middle
      income country (LMIC) centers. We collected data prospectively and then surveyed
      a representative sample of 100 alumni (94% response), assessing Program impacts
      on their careers and collaborations. Frequently, collaborations continued beyond
      the formal training period with U.S.- (63%) and site-based mentors (66%). U.S.
      Fellows reported the highest post-training focus on research (88 on a 100-point
      scale), and the highest Program impact on competitiveness for career or training
      positions and choices of post-training topics and institutions (95 points).
      Interest in global health research increased markedly during the training period,
      especially for LMIC trainees, and was sustained post-training. LMIC alumni
      reported a significantly higher focus on global health and research than did U.S.
      alumni. Alumni reported that their mentored research training had a substantial
      impact on their career trajectories. 

PMID- 26195468
TI  - Nosocomial Cholera Outbreak in a Mental Hospital: Challenges and Lessons Learnt
      from Butabika National Referral Mental Hospital, Uganda.
AB  - During the last four decades, Uganda has experienced repeated cholera outbreaks
      in communities; no cholera outbreaks have been reported in Ugandan health
      facilities. In October 2008, a unique cholera outbreak was confirmed in Butabika
      National Mental Referral Hospital (BNMRH), Uganda. This article describes actions
      taken to control the outbreak, challenges, and lessons learnt. We reviewed
      patient and hospital reports for clinical symptoms and signs, treatment and
      outcome, patient mental diagnosis, and challenges noted during management of
      patients and contacts. Out of 114 BNMRH patients on two affected wards, 18
      cholera cases and five deaths were documented for an attack rate of 15.8% and a
      case fatality rate of 28%. Wards and surroundings were intensively disinfected
      and 96 contacts (psychiatric patients) in the affected wards received
      chemoprophylaxis with oral ciprofloxacin 500 mg twice daily until November 5,
      2008. We documented a nosocomial cholera outbreak in BNMRH with a high case
      fatality of 28% compared with the national average of 2.4% for cholera outbreaks
      in communities. To avoid cholera outbreaks and potentially high mortality among
      patients in mental institutions, procedures for prompt diagnosis, treatment,
      disinfection, and prophylaxis are needed and preemptive use of oral cholera
      vaccines should be considered. 

PMID- 26195467
TI  - Performance Requirements to Achieve Cost-Effectiveness of Point-of-Care Tests for
      Sepsis Among Patients with Febrile Illness in Low-Resource Settings.
AB  - Bacterial sepsis is an important cause of mortality in low- and middle-income
      countries, yet distinguishing patients with sepsis from those with other
      illnesses remains a challenge. Currently, management decisions are based on
      clinical assessment using algorithms such as Integrated Management of Adolescent
      and Adult Illness. Efforts to develop and evaluate point-of-care tests (POCTs)
      for sepsis to guide decisions on the use of antimicrobials are underway. To
      establish the minimum performance characteristics of such a test, we varied the
      characteristics of a hypothetical POCT for sepsis required for it to be cost
      effective and applied a decision tree model to a population of febrile patients
      presenting at the district hospital level in a low-resource setting. We used a
      case fatality probability of 20% for appropriately treated sepsis and of 50% for
      inappropriately treated sepsis. On the basis of clinical assessment for sepsis
      with established sensitivity of 0.83 and specificity of 0.62, we found that a
      POCT for sepsis with a sensitivity of 0.83 and a specificity of 0.94 was cost
      effective, resulting in parity in survival but costing $1.14 less per live saved.
      A POCT with accuracy equivalent to the best malaria rapid diagnostic test was
      cheaper and more effective than clinical assessment. 

PMID- 26195469
TI  - Systematic review and meta-analysis on management of acute urinary retention.
AB  - BACKGROUND: Acute urinary retention (AUR) is a common urological emergency. In
      this article, we review the current literature and present a structured summary
      in management of AUR. METHODS: A systematic review was conducted using the
      keywords 'acute AND retention AND urin*' within the title in search engines
      including Medline, EMBASE and EBM Review. The obtained literature was manually
      reviewed by the primary author (PDY) and was further refined by confining the
      subject to management of AUR. Exclusion criteria included paediatric and female
      population studies, case reports, reviews, surveys, economical assessment and
      articles on AUR in prostate cancer and post-operative patients. RESULTS: Total of
      54 articles met our inclusion and exclusion criteria. The trial without catheter
      (TWOC) post-immediate catheterisation is widely practiced although there remains
      a significant variability in terms of type and duration of catheterisation
      required, use of concurrent medical therapy or post-catheterisation management.
      Our systematic review and subsequent meta-analysis has shown superiority of
      alpha1-adrenergic receptor blockers over placebo in achieving successful voiding
      in patients with AUR. Suprapubic catheter (SPC) is an alternative to urethral
      catheterisation (indwelling catheter (IDC)) and may provide several advantages.
      Clean intermittent self-catheterisation may be a safe and useful option for
      patients with AUR until their definitive management. The overall long-term
      outcome of in-and-out catheterisation remains promising in selected patients.
      Surgery is an end point in patients with unsuccessful TWOC as well as in those
      with significant lower urinary tract symptoms post-successful TWOC. CONCLUSIONS:
      We recommend use of alpha1-adrenergic receptor blockers before TWOC and
      discourage emergency operative management. Use of SPC over IDC in AUR is
      debatable. Duration of catheterisation is controversial but <3 days is a safe
      option in avoiding catheterisation-related complications. Although TURP remains
      the current gold standard, there has been an emergence of newer operative
      management utilising laser techniques.

PMID- 26195471
TI  - Determining Surgical Complications in the Overweight (DISCOVER): a multicentre
      observational cohort study to evaluate the role of obesity as a risk factor for
      postoperative complications in general surgery.
AB  - INTRODUCTION: Obesity is increasingly prevalent among patients undergoing
      surgery. Conflicting evidence exists regarding the impact of obesity on
      postoperative complications. This multicentre study aims to determine whether
      obesity is associated with increased postoperative complications following
      general surgery. METHODS AND ANALYSIS: This prospective, multicentre cohort study
      will be performed utilising a collaborative methodology. Consecutive adults
      undergoing open or laparoscopic, elective or emergency, gastrointestinal,
      bariatric or hepatobiliary surgery will be included. Day case patients will be
      excluded. The primary end point will be the overall 30-day major complication
      rate (Clavien-Dindo grade III-V complications). Data will be collected to risk
      adjust outcomes for potential confounding factors, such as preoperative cardiac
      risk. This study will be disseminated through structured medical student networks
      using established collaborative methodology. The study will be powered to detect
      a two-percentage point increase in the major postoperative complication rate in
      obese versus non-obese patients. ETHICS AND DISSEMINATION: Following appropriate
      assessment, an exemption from full ethics committee review has been received, and
      the study will be registered as a clinical audit or service evaluation at each
      participating hospital. Dissemination will take place through national and local
      research collaborative networks.

PMID- 26195470
TI  - Evolution of multi-parametric MRI quantitative parameters following transrectal
      ultrasound-guided biopsy of the prostate.
AB  - BACKGROUND: To determine the evolution of prostatic multi-parametric magnetic
      resonance imaging (mp-MRI) signal following transrectal ultrasound (TRUS)-guided
      biopsy. METHODS: Local ethical permission and informed written consent was
      obtained from all the participants (n=14, aged 43-69, mean 64 years). Patients
      with a clinical suspicion of prostate cancer (PSA range 2.2-11.7, mean 6.2) and a
      negative (PIRAD 1-2/5) pre-biopsy mp-MRI (pre-contrast T1, T2, diffusion-weighted
      and dynamic-contrast-enhanced MRI) who underwent 10-core TRUS-guided biopsy were
      recruited for additional mp-MRI examinations performed at 1, 2 and 6 months post
      biopsy. We quantified mp-MRI peripheral zone (PZ) and transition zone (TZ)
      normalized T2 signal intensity (nT2-SI); T1 relaxation time (T10); diffusion
      weighted MRI, apparent diffusion coefficient (ADC); dynamic contrast-enhanced
      MRI, maximum enhancement (ME); slope of enhancement (SoE) and area-under-the
      contrast-enhancement-curve at 120 s (AUC120). Significant changes in mp-MRI
      parameters were identified by analysis of variance with Dunnett's post testing.
      RESULTS: Diffuse signal changes were observed post-biopsy throughout the PZ. No
      significant signal change occurred following biopsy within the TZ. Left and right
      PZ mean nT2-SI (left PZ: 5.73, 5.16, 4.90 and 5.12; right PZ: 5.80, 5.10, 4.84
      and 5.05 at pre-biopsy, 1, 2 and 6 months post biopsy, respectively) and mean T10
      (left PZ: 1.02, 0.67, 0.78, 0.85; right PZ: 1.29, 0.64, 0.78, 0.87 at pre-biopsy,
      1, 2 and 6 months post biopsy, respectively) were reduced significantly (P<0.05)
      from pre-biopsy values for up to 6 months post biopsy. Significant changes
      (P<0.05) of PZ-ME and AUC120 were observed at 1 month but resolved by 2 months
      post biopsy. PZ ADC did not change significantly following biopsy (P=0.23-1.0).
      There was no significant change of any TZ mp-MRI parameter at any time point
      following biopsy (P=0.1-1.0). CONCLUSIONS: Significant PZ (but not TZ) T2 signal
      changes persist up to 6 months post biopsy, whereas PZ and TZ ADC is not
      significantly altered as early as 1 month post biopsy. Caution must be exercised
      when interpreting T1- and T2-weighted imaging early post biopsy, whereas ADC
      images are more likely to maintain clinical efficacy.

PMID- 26195472
TI  - Gonorrhoea treatment position statement.

PMID- 26195473
TI  - Achieving public health competencies for genitourinary medicine trainees: a peer
      led education programme.

PMID- 26195474
TI  - An unusual cause of sore throat and neck swelling.

PMID- 26195477
TI  - Correction.

PMID- 26195475
TI  - Towards evidence-based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET: Is CT thorax necessary to exclude significant injury in
      paediatric patients with blunt chest trauma?
AB  - A shortcut review was carried out to establish if CXR had sufficient sensitivity
      to rule out significant thoracic injury in haemodynamically stable, paediatric
      patients with a significant mechanism of trauma. No studies were found that
      directly answered the three-part question, but 13 studies were found which were
      considered relevant. The author, date and country of publication, patient group
      studied, study type, relevant outcomes, results and study weaknesses of these
      papers are tabulated. The clinical bottom line is that important thoracic
      injuries may not be clinically apparent and that CT scans have a significantly
      higher sensitivity than CXR in detecting such injuries. 

PMID- 26195478
TI  - Profibrotic Role for Interleukin-4 in Cardiac Remodeling and Dysfunction.
AB  - Elevated interleukin-4 (IL-4) levels are associated with cardiac fibrosis in
      hypertension and heart failure in both patients and experimental animals. We
      hypothesized that chronically elevated IL-4 induces cardiac fibrosis, resulting
      in a predisposition of the heart to angiotensin II-induced damage. Wild-type
      Balb/c (WT, high circulating IL-4) and IL-4-deficient Balb/c mice (IL-4(-/-))
      were used. WT mice exhibited cardiac fibrosis (evidenced by an increase in
      expression of procollagen genes/interstitial collagen fraction), enlarged left
      ventricle chamber, and declined cardiac function associated with a greater number
      of mast cells and macrophages in the heart compared with IL-4(-/-). In contrast,
      IL-4(-/-) mice had normal cardiac architecture/function while showing a 57.9%
      reduction in heart interstitial collagen compared with WT, despite elevated
      proinflammatory cytokines in heart tissue. In response to angiotensin II
      administration, IL-4(-/-) had reduced interstitial myocardial fibrosis and were
      protected from developing dilated cardiomyopathy, which was seen in WT mice. This
      was associated with increased macrophage infiltration into the hearts of WT mice,
      despite a similar degree of hypertension and increased cardiac transforming
      growth factor-beta1 in both groups. In vitro data demonstrated that IL-4
      upregulates procollagen genes and stimulates collagen production in mouse cardiac
      fibroblasts. This process is mediated by signal transducer and activator of
      transcription 6 signaling pathway via IL-4 receptor alpha. This study not only
      establishes a causal relationship between IL-4 and cardiac fibrosis/dysfunction,
      but also reveals a critical role for IL-4 in angiotensin II-induced cardiac
      damage. IL-4 could serve as an additional target for the treatment of cardiac
      fibrosis. 

PMID- 26195479
TI  - Role of Chemoreceptor Activation in Hemodynamic Responses to Electrical
      Stimulation of the Carotid Sinus in Conscious Rats.
AB  - Electric carotid baroreflex activation has been used to treat patients with
      resistant hypertension. It is hypothesized that, in conscious rats, combined
      activation of carotid baro- and chemoreceptors afferences attenuates the reflex
      hypotension. Rats were divided into 4 groups: (1) control group, with unilateral
      denervation of the right carotid chemoreceptors; (2) chemoreceptor denervation
      group, with bilateral ligation of the carotid body artery; (3) baroreceptor
      denervation group, with unilateral denervation of the left carotid baroreceptors
      and right carotid chemoreceptors; and (4) carotid bifurcation denervation group,
      with denervation of the left carotid baroreceptors and chemoreceptors, plus
      denervation of the right carotid chemoreceptors. Animals were subjected to 4
      rounds of electric stimulation (5 V, 1 ms), with 15, 30, 60, and 90 Hz applied
      randomly for 20 s. Electric stimulation caused greater hypotensive responses in
      the chemoreceptor denervation group than in the control group, at 60 Hz (-37
      versus -19 mm Hg) and 90 Hz (-33 versus -19 mm Hg). The baroreceptor denervation
      group showed hypertensive responses at all frequencies of stimulation. In
      contrast, the carotid sinus denervation group showed no hemodynamic responses.
      The control group presented no changes in heart rate, whereas the chemoreceptor
      denervation group and the baroreceptor denervation group showed bradycardic
      responses. These data demonstrate that carotid chemoreceptor activation
      attenuates the reflex hypotension caused by combined electric stimulation of the
      carotid sinus and the carotid sinus nerve in conscious rats. These findings may
      provide useful insight for clinical studies using baroreflex activation therapy
      in resistant hypertension and heart failure. 

PMID- 26195480
TI  - Plasma 1,25-Dihydroxyvitamin D and the Risk of Developing Hypertension: The
      Prevention of Renal and Vascular End-Stage Disease Study.
AB  - Previous observational studies on the vascular effects of vitamin D have
      predominantly relied on measurement of its inactive precursor, 25-hydroxyvitamin
      D, whereas the active metabolite 1,25-dihydroxyvitamin D may be of more
      physiological relevance. We prospectively studied the associations of 1,25
      dihydroxyvitamin D and 25-hydroxyvitamin D with hypertension risk (blood pressure
      >=140/90 mm Hg or initiation of blood pressure-lowering drugs) in 5066
      participants aged 28 to 75 years, free of hypertension at baseline from the
      Prevention of Renal and Vascular End-Stage Disease Study, a well-defined cohort
      with serial follow-up. We measured plasma 1,25-dihydroxyvitamin D and 25
      hydroxyvitamin D using liquid chromatography-tandem mass spectrometry. Mean+/-SD
      plasma concentration of 1,25-dihydroxyvitamin D was 145+/-47.0 pmol/L and 25
      hydroxyvitamin D was 58.6+/-23.8 nmol/L. During a median follow-up of 6.4 years,
      1036 participants (20.5%) developed hypertension. As expected, low 25
      hydroxyvitamin D was associated with a higher hypertension risk; each 1-SD
      decrement in 25-hydroxyvitamin D was associated with a 8% higher hypertension
      risk (hazard ratio, 1.08; 95% confidence interval, 1.01-1.16) after adjustment
      for potential confounders. However, the association of 1,25-dihydroxyvitamin D
      was in the opposite direction; each 1-SD decrement of 1,25-dihydroxyvitamin D was
      associated with a 10% lower hypertension risk (hazard ratio, 0.90; 95% confidence
      interval, 0.84-0.96), independent of potential confounders. In contrast to the
      inverse association between 25-hydroxyvitamin D and hypertension risk, 1,25
      dihydroxyvitamin D was positively associated with risk of hypertension. Thus,
      higher circulating concentrations of 1,25-dihydroxyvitamin D are associated with
      a higher risk of hypertension. 

PMID- 26195482
TI  - Longitudinal and Secular Trends in Blood Pressure Among Women and Men in Birth
      Cohorts Born Between 1905 and 1977: The Tromso Study 1979 to 2008.
AB  - High blood pressure is a modifiable risk factor for cardiovascular disease.
      Previous studies showing a blood pressure decline in recent decades lack data to
      follow individuals born in different decades from early and middle adulthood to
      older age. We investigated changes in age-specific blood pressure by repeated
      measurements in 37973 women and men born 1905 to 1977 (aged 20-89 years) examined
      <=5* between 1979 and 2008 in the population-based Tromso Study. Mixed models
      were used to estimate time trends. Mean systolic and diastolic blood pressure
      decreased from 1979 to 2008 in both genders in the age groups 30 to 89 years. The
      decrease was similar in the 80th percentile and the 20th percentile of the
      population blood pressure distribution. The decrease in systolic blood pressure
      in age group 40 to 49 years was 10.6 mm Hg in women and 4.5 mm Hg in men.
      Systolic blood pressure increased with age in women and men born 1920 to 1949,
      whereas a decrease or flattening of curve was observed in the younger birth
      cohorts. Thus, we found both time periodic and cohort effects, and trends were
      more pronounced in women than in men. The findings suggest changes in blood
      pressure in the population rather than an effect of treatment of high-risk
      individuals. 

PMID- 26195481
TI  - Dual Activation of TRIF and MyD88 Adaptor Proteins by Angiotensin II Evokes
      Opposing Effects on Pressure, Cardiac Hypertrophy, and Inflammatory Gene
      Expression.
AB  - Hypertension is recognized as an immune disorder whereby immune cells play a
      defining role in the genesis and progression of the disease. The innate immune
      system and its component toll-like receptors are key determinants of the
      immunologic outcome through their proinflammatory response. Toll-like receptor
      activated signaling pathways use several adaptor proteins of which adaptor
      proteins myeloid differentiation protein 88 (MyD88) and toll-interleukin receptor
      domain-containing adaptor protein-inducing interferon-beta (TRIF) define 2 major
      inflammatory pathways. In this study, we compared the contributions of MyD88 and
      TRIF adaptor proteins to angiotensin II (Ang II)-induced hypertension and cardiac
      hypertrophy in mice. Deletion of MyD88 did not prevent cardiac hypertrophy and
      the pressor response to Ang II tended to increase. Moreover, the increase in
      inflammatory gene expression (Tnfa, Nox4, and Agtr1a) was significantly greater
      in the heart and kidney of MyD88-deficient mice when compared with wild-type
      mice. Thus, pathways involving MyD88 may actually restrain the inflammatory
      responses. However, in mice with nonfunctional TRIF (Trif(mut) mice), Ang II
      induced hypertension and cardiac hypertrophy were abrogated, and proinflammatory
      gene expression in heart and kidneys was unchanged or decreased. Our results
      indicate that Ang II induces activation of a proinflammatory innate immune
      response, causing hypertension and cardiac hypertrophy. These effects require
      functional adaptor protein TRIF-mediated pathways. However, the common MyD88
      dependent signaling pathway, which is also activated simultaneously by Ang II,
      paradoxically exerts a negative regulatory influence on these responses. 

PMID- 26195483
TI  - Aldosterone and Salt Loading Independently Exacerbate the Exercise Pressor Reflex
      in Rats.
AB  - The sympathetic and pressor responses to exercise are exaggerated in
      hypertension. Evidence suggests that an overactive exercise pressor reflex (EPR)
      contributes to this abnormal responsiveness. The mechanisms underlying this EPR
      overactivity are poorly understood. An increasing body of evidence suggests that
      aldosterone and excessive salt intake play a role in regulating resting
      sympathetic activity and blood pressure in hypertension. Therefore, each is a
      good candidate for the generation of EPR dysfunction in this disease. The purpose
      of this study was to examine whether excessive salt intake and chronic
      administration of aldosterone potentiate EPR function. Changes in mean arterial
      pressure and renal sympathetic nerve activity induced by EPR stimulation were
      examined in vehicle and aldosterone-treated (4 weeks via osmotic mini-pump)
      Sprague-Dawley rats given either water or saline (elevated salt load) to drink.
      When compared with vehicle/water-treated rats, stimulation of the EPR by muscle
      contraction evoked significantly greater increases in mean arterial pressure in
      vehicle/saline, aldosterone/water, and aldosterone/saline-treated animals (14+/
      3, 29+/-3, 37+/-6, and 44+/-7 mm Hg/kg, respectively; P<0.01). A similar renal
      sympathetic nerve activity response profile was likewise produced (39+/-11%, 87+/
      15%, 110+/-20%, and 151+/-25%/kg, respectively; P<0.01). The pressor and
      sympathetic responses to the individual activation of the mechanically and
      chemically sensitive components of the EPR were also augmented by both saline and
      aldosterone. These data provide the first direct evidence that both aldosterone
      and high salt intake elicit EPR overactivity. As such, each represents a
      potential mechanism by which sympathetic activity and blood pressure are
      augmented during exercise in hypertension. 

PMID- 26195484
TI  - Greater Sensitivity of Blood Pressure Than Renal Toxicity to Tyrosine Kinase
      Receptor Inhibition With Sunitinib.
AB  - Hypertension and renal injury are off-target effects of sunitinib, a tyrosine
      kinase receptor inhibitor used for the treatment of various tumor types.
      Importantly, these untoward effects are accompanied by activation of the
      endothelin system. Here, we set up a study to explore the dose dependency of
      these side effects. Normotensive Wistar Kyoto rats were exposed to 3 different
      doses of sunitinib or vehicle. After 8 days, rats were euthanized. Telemetrically
      measured blood pressure rose dose dependently, from 13 to 30 mm Hg. Proteinuria
      was present at all doses, but a rise in cystatin C occurred only at the
      intermediate and high doses. Compared with vehicle circulating endothelin-1
      increased dose dependently, whereas 24-hour urinary endothelin excretion
      decreased. Light and electron microscopy revealed glomerular endotheliosis and
      ischemia with the intermediate and high doses of sunitinib but completely absent
      histological abnormalities with the low dose. Podocyte number per glomerular
      circumference did not change. Glomerular nephrin, Neph1, podocin, and endothelin
      converting enzyme gene expression were downregulated in a dose-dependent manner.
      We conclude that the sunitinib-induced rise in blood pressure requires lower
      doses than its induction of renal function impairment and that functional changes
      in glomerular filtration barrier contribute to the occurrence of proteinuria,
      given the lack of histopathologic changes with the low dose of sunitinib. 

PMID- 26195485
TI  - Monitoring and reporting of preanalytical errors in laboratory medicine: the UK
      situation.
AB  - BACKGROUND: Most errors in the clinical laboratory occur in the preanalytical
      phase. This study aimed to comprehensively describe the prevalence and nature of
      preanalytical quality monitoring practices in UK clinical laboratories. METHODS:
      A survey was sent on behalf of the Association for Clinical Biochemistry and
      Laboratory Medicine Preanalytical Working Group (ACB-WG-PA) to all heads of
      department of clinical laboratories in the UK. The survey captured data on the
      analytical platform and Laboratory Information Management System in use; which
      preanalytical errors were recorded and how they were classified and gauged
      interest in an external quality assurance scheme for preanalytical errors.
      RESULTS: Of the 157 laboratories asked to participate, responses were received
      from 104 (66.2%). Laboratory error rates were recorded per number of specimens,
      rather than per number of requests in 51% of respondents. Aside from serum
      indices for haemolysis, icterus and lipaemia, which were measured in 80% of
      laboratories, the most common errors recorded were booking-in errors (70.1%) and
      sample mislabelling (56.9%) in laboratories who record preanalytical errors. Of
      the laboratories surveyed, 95.9% expressed an interest in guidance on recording
      preanalytical error and 91.8% expressed interest in an external quality assurance
      scheme. CONCLUSIONS: This survey observes a wide variation in the definition,
      repertoire and collection methods for preanalytical errors in the UK. Data
      indicate there is a lot of interest in improving preanalytical data collection.
      The ACB-WG-PA aims to produce guidance and support for laboratories to
      standardize preanalytical data collection and to help establish and validate an
      external quality assurance scheme for interlaboratory comparison.

PMID- 26195486
TI  - The impact of change in albumin assay on reference intervals, prevalence of
      'hypoalbuminaemia' and albumin prescriptions.
AB  - BACKGROUND: We studied the impact on reference intervals, classification of
      patients with hypoalbuminaemia and albumin infusion prescriptions on changing
      from a bromocresol green (BCG) to a bromocresol purple (BCP) serum albumin assay.
      METHODS: Passing-Bablok regression analysis and Bland-Altman plot were used to
      compare Abbott BCP and Roche BCG methods. Linear regression analysis was used to
      compare in-house and an external laboratory Abbott BCP serum albumin results.
      Reference intervals for Abbott BCP serum albumin were derived in two different
      laboratories using pathology data from adult patients in primary care.
      Prescriptions for 20% albumin infusions were compared one year before and one
      year after changing the albumin method. RESULTS: Abbott BCP assay had a negative
      bias of approximately 6 g/L compared with Roche BCG method.There was good
      agreement (y = 1.04 x - 1.03; R(2 )= 0.9933) between in-house and external
      laboratory Abbott BCP results. Reference intervals for the serum albumin Abbott
      BCP assay were 31-45 g/L, different to those recommended by Pathology Harmony and
      the manufacturers (35-50 g/L). Following the change in method there was a large
      increase in the number of patients classified as hypoalbuminaemic using Pathology
      Harmony references intervals (32%) but not when retrospectively compared to
      locally derived reference intervals (16%) compared with the previous year (12%).
      The method change was associated with a 44.6% increase in albumin prescriptions.
      This equated to an annual increase in expenditure of L35,234. CONCLUSIONS: We
      suggest that serum albumin reference intervals be method specific to prevent
      misclassification of albumin status in patients. Change in albumin methodology
      may have significant impact on hospital resources.

PMID- 26195487
TI  - A novel high-throughput method for supported liquid extraction of retinol and
      alpha-tocopherol from human serum and simultaneous quantitation by liquid
      chromatography tandem mass spectrometry.
AB  - BACKGROUND: Measurement of vitamin A (retinol) and E (alpha-tocopherol) in UK
      clinical laboratories is currently performed exclusively by high-performance
      liquid chromatography with ultraviolet detection. We investigated whether retinol
      and alpha-tocopherol could be measured simultaneously by liquid chromatography
      tandem mass spectrometry. METHODS: Serum samples (100 MUL) were extracted using
      Isolute + Supported Liquid Extraction plates. Chromatography was performed on a
      Phenomenex Kinetex Biphenyl 2.6 MUm, 50 * 2.1 mm column, and liquid
      chromatography tandem mass spectrometry on a Waters Acquity TQD. Injection-to
      injection time was 4.3 min. The assay was validated according to published
      guidelines. Patient samples were used to compare liquid chromatography tandem
      mass spectrometry and high-performance liquid chromatography with ultraviolet
      detection methods. RESULTS: For retinol and alpha-tocopherol, respectively, the
      assay was linear up to 6.0 and 80.0 MUmol/L, and lower limit of quantification
      was 0.07 and 0.26 MUmol/L. Intra and interassay imprecision were within desirable
      analytical specifications. Analysis of quality control material aligned to NIST
      SRM 968e, and relative spiked recovery from human serum, both yielded results
      within 15% of target values. Method comparison with high-performance liquid
      chromatography with ultraviolet detection methodology demonstrated a negative
      bias for retinol and alpha-tocopherol by the liquid chromatography tandem mass
      spectrometry method. Analysis of United Kingdom National External Quality
      Assurance Scheme samples yielded mean bias from the target value of +3.0% for
      retinol and -11.2% for alpha-tocopherol. CONCLUSIONS: We have developed a novel,
      high-throughput method for extraction of retinol and alpha-tocopherol from human
      serum followed by simultaneous quantitation by liquid chromatography tandem mass
      spectrometry. The method offers a rapid, sensitive, specific and cost-effective
      alternative to high-performance liquid chromatography with ultraviolet detection
      methodology, and is suitable for routine clinical monitoring of patients
      predisposed to fat-soluble vitamin malabsorption.

PMID- 26195488
TI  - Overuse of Cardiovascular Services: Evidence, Causes, and Opportunities for
      Reform.

PMID- 26195489
TI  - ECG Response: July 21, 2015.

PMID- 26195490
TI  - Repetitive Artery-to-Artery Embolism Caused by Dynamic Movement of the Internal
      Carotid Artery and Mechanical Stimulation by the Hyoid Bone.

PMID- 26195491
TI  - Letter by Hoenselaar Regarding Article, "Dietary Linoleic Acid and Risk of
      Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective
      Cohort Studies".

PMID- 26195492
TI  - Letter by Lucas Regarding Articles, "Dietary Linoleic Acid and Risk of Coronary
      Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort
      Studies" and "Circulating Omega-6 Polyunsaturated Fatty Acids and Total and Cause
      Specific Mortality: The Cardiovascular Health Study".

PMID- 26195493
TI  - Letter by Sertoglu et al Regarding Article, "Circulating Omega-6 Polyunsaturated
      Fatty Acids and Total and Cause-Specific Mortality: The Cardiovascular Health
      Study".

PMID- 26195494
TI  - Response to Letters Regarding Article, "Dietary Linoleic Acid and Risk of
      Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective
      Cohort Studies".

PMID- 26195496
TI  - Corrigendum.
AB  - R. Jeffrey Neitz, Steven Chen, Frantisek Supek, Vince Yeh, Danielle Kellar, Jiri
      Gut, Clifford Bryant, Alejandra Gallardo-Godoy, Valentina Molteni, Steven L.
      Roach, Arnab K. Chatterjee, Stephanie Robertson, Adam R. Renslo, Michelle Arkin,
      Richard Glynne, James McKerrow, and Jair L. Siqueira-Neto. Lead Identification to
      Clinical Candidate Selection: Drugs for Chagas Disease J. Biomol. Screen. 2015,
      20, 101-111. (Original doi:10.1177/1087057114553103)In the January 2015 issue of
      the Journal of Biomolecular Screening, the names of two authors were not
      published with this article, Shilpi Khare and Monique Stinson. Their names should
      have appeared after Steven L. Roach, and the affiliation for both of the missing
      authors is the Genomics Institute of the Novartis Research Foundation (GNF), San
      Diego, CA, USA. 

PMID- 26195495
TI  - Response to Letters Regarding Article, "Circulating Omega-6 Polyunsaturated Fatty
      Acids and Total and Cause-Specific Mortality: The Cardiovascular Health Study".

PMID- 26195497
TI  - Transformative Impact of Proteomics on Cardiovascular Health and Disease: A
      Scientific Statement From the American Heart Association.
AB  - The year 2014 marked the 20th anniversary of the coining of the term proteomics.
      The purpose of this scientific statement is to summarize advances over this
      period that have catalyzed our capacity to address the experimental,
      translational, and clinical implications of proteomics as applied to
      cardiovascular health and disease and to evaluate the current status of the
      field. Key successes that have energized the field are delineated; opportunities
      for proteomics to drive basic science research, facilitate clinical translation,
      and establish diagnostic and therapeutic healthcare algorithms are discussed; and
      challenges that remain to be solved before proteomic technologies can be readily
      translated from scientific discoveries to meaningful advances in cardiovascular
      care are addressed. Proteomics is the result of disruptive technologies, namely,
      mass spectrometry and database searching, which drove protein analysis from 1
      protein at a time to protein mixture analyses that enable large-scale analysis of
      proteins and facilitate paradigm shifts in biological concepts that address
      important clinical questions. Over the past 20 years, the field of proteomics has
      matured, yet it is still developing rapidly. The scope of this statement will
      extend beyond the reaches of a typical review article and offer guidance on the
      use of next-generation proteomics for future scientific discovery in the basic
      research laboratory and clinical settings. 

PMID- 26195498
TI  - Delivery of Apical Mesenchymal Stem Cells into Root Canals of Mature Teeth.
AB  - Regenerative endodontic procedures are stem cell-based treatments for immature
      teeth with pulp necrosis. The translation of regenerative endodontic procedures
      into treating mature teeth depends, among other factors, on the availability and
      delivery of mesenchymal stem cells (MSCs) into the root canal system. The aim of
      this clinical study was to evaluate whether evoked bleeding from the periapical
      tissues elicits the influx of MSCs into the root canal system in mature teeth
      with apical lesions. Participants included in this study (N = 20) were referred
      for endodontic treatment of mature teeth with apical lesions. Following
      chemomechanical debridement, intracanal bleeding from the periapical tissues was
      achieved, and intracanal blood samples were collected. A positive blood aspirate
      was also collected in the cartridges during local anesthesia. Total RNA was
      isolated and used as a template in quantitative reverse transcription polymerase
      chain reactions using MSC-specific arrays. Data were analyzed with the Wilcoxon
      signed-rank test, and correlation between gene expression and sex or age was
      tested with Spearman's rank correlation coefficient test. In addition, MSCs were
      isolated from an intracanal bleeding sample and subjected to flow cytometry and
      quantitative osteogenesis assay. Last, the presence and distribution of MSCs
      within periradicular lesions were evaluated with immunohistochemistry (n = 4).
      The MSC markers CD73, CD90, CD105, and CD146 were significantly upregulated, with
      median fold change values of 2.9, 31.7, 4.6, and 6.8, respectively. Conversely,
      the negative marker for MSCs, CD45, was significantly downregulated (median, 
      2.7). There was no correlation with age, sex, tooth type, or treatment for any of
      the evaluated genes. Isolated intracanal cells coexpressed MSC markers and
      demonstrated robust mineralizing differentiation potential. Finally,
      immunohistochemical analysis revealed that MSCs were found compartmentalized
      mainly within vasculature structures located in periapical lesions. Collectively,
      findings indicate that the evoked-bleeding technique delivers MSCs into the root
      canal system in mature teeth with apical lesions. 

PMID- 26195499
TI  - Perceptions of Successful Aging: Intergenerational Voices Value Well-Being.
AB  - This study explored the perceptions of successful aging from intergenerational
      perspectives. A total of 66 participants were interviewed from three different
      generations including college students, parents, and grandparents. After
      qualitative data collection and analyses were used, five conceptual categories
      emerged from the data that related to perceptions of successful aging. The five
      concepts include wisdom, health, financial stability, staying active, and well
      being. Conceptual categories emerged from the participants of different
      generations, and some were interconnected across generations. Each category is
      representative of major thematic patterns. Well-being was the primary concept
      which emerged because all three generations perceived and explicitly discussed
      well-being as the most valued aspect of successful aging. Previous successful
      aging research informed the use of a bio-psycho-social theoretical lens to frame
      the study findings and discussion. 

PMID- 26195500
TI  - Depressive Symptoms of Older Adults Living Alone: The Role of Community
      Characteristics.
AB  - Although some evidence suggests that community characteristics may play an
      important role in the development of depressive symptoms among older adults,
      current literature has not attended to the role of community characteristics in
      depression in South Korea. This study begins to address this gap in the
      literature by examining the relationship of community characteristics and
      depressive symptoms, controlling for individual characteristics. Using a cross
      sectional design and probability sampling, we surveyed 949 older adults living
      alone in 70 communities in the Busan metropolitan area in South Korea in 2012. A
      multilevel logistic regression analysis was conducted to test the hypothesis that
      community characteristics are predictive of depressive symptoms. We find that
      both the proportion of older adults and the number of senior citizen facilities
      in a community are associated with depressive symptoms, whereas community poverty
      is not related to depressive symptoms. Men with lower income, with lower levels
      of functional abilities, and without stronger family and friend social networks
      have a higher risk of depressive symptoms. Implications for research, practice,
      and policy are discussed. 

PMID- 26195501
TI  - Examining the Positivity Effect in Autobiographical Memory Across Adulthood.
AB  - The positivity effect in memory is characterized by enhanced memory for
      emotionally positive information or decreased memory for emotionally negative
      information with increased age. The goals of the current study were to (a)
      examine the positivity effect in autobiographical memory using instructions that
      limited experimental constraints, (b) examine the relationship between memory
      valence and subjective well-being, and (c) examine the relationship between age
      and other memory characteristics across adulthood. In the current study, 281
      individuals between the ages of 18 and 94 (Mage=53.14, SD=17.04) completed a
      modified Memory Experiences Questionnaire using online survey methods.
      Participants answered questions about emotional valence and other
      phenomenological characteristics regarding two memories, including any specific
      memory of their choosing and a personally meaningful memory. Results indicated
      that memory valence was unrelated to age, thus failing to provide evidence for
      the positivity effect. However, memory valence was found to be a significant
      predictor of life satisfaction. Age moderated the relationship between memory
      valence and subjective well-being but did so differently across the two memories.
      Age was also associated with increased vividness, coherence, sensory detail, time
      clarity, and a first-person perspective for the personally meaningful memory.

PMID- 26195502
TI  - Validation of the K6/K10 Scales of Psychological Distress and Their Optimal
      Cutoff Scores for Older Koreans.
AB  - This study aims to assess the psychometric properties of the Korean versions of
      the Kessler 6 and 10 (K-K6/K10) to validate the two scales in relation to the
      Korean versions of the Geriatric Depression Scale-Short Form (K-GDS-SF) and the
      Center for Epidemiological Studies Depression Scale (K-CES-D) and to propose
      optimal cutoff scores appropriate for the elderly Korean population (n=331).
      Psychometric performance was assessed with sensitivity, specificity, receiver
      operating characteristic curves, and area under the receiver operating
      characteristic curve. Cutoff scores were estimated from the Youden index, the
      closest-to-(0,1), and the balanced score. This study found that the K-K6 and K
      K10 appeared to be robust screening tools, with the K-CES-D and K-GDS-SF as
      reference measures. The cutoff scores for the Korean senior population are
      proposed to be 12/13 for the K-K6 and 20/21 for the K-K10. This study indicates
      that the K6 and K10 can be valid and reliable screening tools of psychological
      distress for Korean seniors and may also be used among the Korean American
      elderly in the United States for both clinical and research purposes.

PMID- 26195503
TI  - Corrigendum.

PMID- 26195504
TI  - Lower Dialysate Temperature in Hemodialysis: Is It a Cool Idea?

PMID- 26195506
TI  - An Excision-Competent and Exogenous Mosaic Transposon Harbors the tetM Gene in
      Multiple Mycoplasma hominis Lineages.

PMID- 26195505
TI  - A Prospective International Multicenter Study of AKI in the Intensive Care Unit.
AB  - BACKGROUND AND OBJECTIVES: AKI is frequent and is associated with poor outcomes.
      There is limited information on the epidemiology of AKI worldwide. This study
      compared patients with AKI in emerging and developed countries to determine the
      association of clinical factors and processes of care with outcomes. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective observational study was
      conducted among intensive care unit patients from nine centers in developed
      countries and five centers in emerging countries. AKI was defined as an increase
      in creatinine of >=0.3 mg/dl within 48 hours. RESULTS: Between 2008 and 2012,
      6647 patients were screened, of whom 1275 (19.2%) developed AKI. A total of 745
      (58% of those with AKI) agreed to participate and had complete data. Patients in
      developed countries had more sepsis (52.1% versus 38.0%) and higher Acute
      Physiology and Chronic Health Evaluation (APACHE) scores (mean+/-SD, 61.1+/-27.5
      versus 51.1+/-25.2); those from emerging countries had more CKD (54.3% versus
      38.3%), GN (6.3% versus 0.9%), and interstitial nephritis (7.0% versus 0.6%) (all
      P<0.05). Patients from developed countries were less often treated with dialysis
      (15.5% versus 30.2%; P<0.001) and started dialysis later after AKI diagnosis (2.0
      [interquartile range, 0.75-5.0] days versus 0 [interquartile range, 0-5.0] days;
      P=0.02). Hospital mortality was 22.0%, and 13.3% of survivors were dialysis
      dependent at discharge. Independent risk factors associated with hospital
      mortality included older age, residence in an emerging country, use of
      vasopressors (emerging countries only), dialysis and mechanical ventilation, and
      higher APACHE score and cumulative fluid balance (developed countries only). A
      lower probability of renal recovery was associated with residence in an emerging
      country, higher APACHE score (emerging countries only) and dialysis, while
      mechanical ventilation was associated with renal recovery (developed countries
      only). CONCLUSIONS: This study contrasts the clinical features and management of
      AKI and demonstrates worse outcomes in emerging than in developed countries.
      Differences in variations in care may explain these findings and should be
      considered in future trials.

PMID- 26195508
TI  - First Report of Ceftazidime-Avibactam Resistance in a KPC-3-Expressing Klebsiella
      pneumoniae Isolate.
AB  - Ceftazidime-avibactam is the first antimicrobial approved by the U.S. FDA for the
      treatment of carbapenem-resistant Enterobacteriaceae. Avibactam, a non-beta
      lactam beta-lactamase inhibitor, inactivates class A serine carbapenemases,
      including Klebsiella pneumoniae carbapenemase (KPC). We report a KPC-producing K.
      pneumoniae isolate resistant to ceftazidime-avibactam (MIC, 32/4 MUg/ml) from a
      patient with no prior treatment with ceftazidime-avibactam. 

PMID- 26195507
TI  - Pharmacokinetics and Safety of Ofloxacin in Children with Drug-Resistant
      Tuberculosis.
AB  - Ofloxacin is widely used for the treatment of multidrug-resistant tuberculosis
      (MDR-TB). Data on its pharmacokinetics and safety in children are limited. It is
      not known whether the current internationally recommended pediatric dosage of 15
      to 20 mg/kg of body weight achieves exposures reached in adults with tuberculosis
      after a standard 800-mg dose (adult median area under the concentration-time
      curve from 0 to 24 h [AUC0-24], 103 MUg . h/ml). We assessed the pharmacokinetics
      and safety of ofloxacin in children <15 years old routinely receiving ofloxacin
      for MDR-TB treatment or preventive therapy. Plasma samples were collected predose
      and at 1, 2, 4, 8, and either 6 or 11 h after a 20-mg/kg dose. Pharmacokinetic
      parameters were calculated using noncompartmental analysis. Children with MDR-TB
      disease underwent long-term safety monitoring. Of 85 children (median age, 3.4
      years), 11 (13%) were HIV infected, and of 79 children with evaluable data, 14
      (18%) were underweight. The ofloxacin mean (range) maximum concentration (Cmax),
      AUC0-8, and half-life were 8.97 MUg/ml (2.47 to 14.4), 44.2 MUg . h/ml (12.1 to
      75.8), and 3.49 h (1.89 to 6.95), respectively. The mean AUC0-24, estimated in 72
      participants, was 66.7 MUg . h/ml (range, 18.8 to 120.7). In multivariable
      analysis, AUC0-24 was increased by 1.46 MUg . h/ml for each 1-kg increase in body
      weight (95% confidence interval [CI], 0.44 to 2.47; P = 0.006); no other assessed
      variable contributed to the model. No grade 3 or 4 events at least possibly
      attributed to ofloxacin were observed. Ofloxacin was safe and well tolerated in
      children with MDR-TB, but exposures were well below reported adult values,
      suggesting that dosage modification may be required to optimize MDR-TB treatment
      regimens in children. 

PMID- 26195509
TI  - Baseline Polymorphisms and Emergence of Drug Resistance in the NS3/4A Protease of
      Hepatitis C Virus Genotype 1 following Treatment with Faldaprevir and Pegylated
      Interferon Alpha 2a/Ribavirin in Phase 2 and Phase 3 Studies.
AB  - Analysis of data pooled from multiple phase 2 (SILEN-C1 to 3) and phase 3 studies
      (STARTVerso1 to 4) of the hepatitis C virus (HCV) nonstructural protein 3/4A
      (NS3/4A) protease inhibitor faldaprevir plus pegylated interferon alpha/ribavirin
      (PR) provides a comprehensive evaluation of baseline and treatment-emergent
      NS3/4A amino acid variants among HCV genotype-1 (GT-1)-infected patients. Pooled
      analyses of GT-1a and GT-1b NS3 population-based pretreatment sequences (n =
      3,124) showed that faldaprevir resistance-associated variants (RAVs) at NS3 R155
      and D168 were rare (<1%). No single, noncanonical NS3 protease or NS4A cofactor
      baseline polymorphism was associated with a reduced sustained virologic response
      (SVR) to faldaprevir plus PR, including Q80K. The GT-1b NS3 helicase polymorphism
      T344I was associated with reduced SVR to faldaprevir plus PR (P < 0.0001) but was
      not faldaprevir specific, as reduced SVR was also observed with placebo plus PR.
      Among patients who did not achieve SVR and had available NS3 population sequences
      (n = 507 GT-1a; n = 349 GT-1b), 94% of GT-1a and 83% of GT-1b encoded faldaprevir
      treatment-emergent RAVs. The predominant GT-1a RAV was R155K (88%), whereas GT-1b
      encoded D168 substitutions (78%) in which D168V was predominant (67%). The novel
      GT-1b NS3 S61L substitution emerged in 7% of virologic failures as a covariant
      with D168V, most often among the faldaprevir breakthroughs; S61L in combination
      with D168V had a minimal impact on faldaprevir susceptibility compared with that
      for D168V alone (1.5-fold difference in vitro). The median time to loss of D168
      RAVs among GT-1b-infected patients who did not have a sustained virologic
      response at 12 weeks posttreatment (non-SVR12) after virologic failure was 5
      months, which was shorter than the 14 months for R155 RAVs among GT-1a-infected
      non-SVR12 patients, suggesting that D168V is less fit than R155K in the absence
      of faldaprevir selective pressure. 

PMID- 26195510
TI  - Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in
      Candida albicans.
AB  - Fungal infections, especially infections caused by Candida albicans, remain a
      challenging problem in clinical settings. Despite the development of more
      effective antifungal drugs, their application is limited for various reasons.
      Thus, alternative treatments with drugs aimed at novel targets in C. albicans are
      needed. Knowledge of growth and virulence in fungal cells is essential not only
      to understand their pathogenic mechanisms but also to identify potential
      antifungal targets. This article reviews the current knowledge of the mechanisms
      of growth and virulence in C. albicans and examines potential targets for the
      development of new antifungal drugs. 

PMID- 26195511
TI  - Emergence of Extensively Drug-Resistant Proteus mirabilis Harboring a Conjugative
      NDM-1 Plasmid and a Novel Salmonella Genomic Island 1 Variant, SGI1-Z.
AB  - Acquisition of blaNDM-1 in bacterial species, such as Proteus mirabilis that is
      intrinsically resistant to tetracycline, tigecycline and colistin, will make
      clinical treatment extremely difficult. Here, we characterized an NDM-1-producing
      clinical isolate of P. mirabilis (PM58) that displayed an extensively drug
      resistant (XDR) phenotype, susceptible only to aztreonam. Molecular analysis
      revealed that PM58 harbored both a conjugative NDM-1 plasmid and a novel
      Salmonella genomic island 1 variant on chromosome. 

PMID- 26195512
TI  - Garcinia xanthochymus Benzophenones Promote Hyphal Apoptosis and Potentiate
      Activity of Fluconazole against Candida albicans Biofilms.
AB  - Xanthochymol and garcinol, isoprenylated benzophenones purified from Garcinia
      xanthochymus fruits, showed multiple activities against Candida albicans
      biofilms. Both compounds effectively prevented emergence of fungal germ tubes and
      were also cytostatic, with MICs of 1 to 3 MUM. The compounds therefore inhibited
      development of hyphae and subsequent biofilm maturation. Xanthochymol treatment
      of developing and mature biofilms induced cell death. In early biofilm
      development, killing had the characteristics of apoptosis, including
      externalization of phosphatidyl serine and DNA fragmentation, as evidenced by
      terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling
      (TUNEL) fluorescence. These activities resulted in failure of biofilm maturation
      and hyphal death in mature biofilms. In mature biofilms, xanthochymol and
      garcinol caused the death of biofilm hyphae, with 50% effective concentrations
      (EC50s) of 30 to 50 MUM. Additionally, xanthochymol-mediated killing was
      complementary with fluconazole against mature biofilms, reducing the fluconazole
      EC50 from >1,024 MUg/ml to 13 MUg/ml. Therefore, xanthochymol has potential as an
      adjuvant for antifungal treatments as well as in studies of fungal apoptosis. 

PMID- 26195513
TI  - A Plasmid Bearing the bla(CTX-M-15) Gene and Phage P1-Like Sequences from a
      Sequence Type 11 Klebsiella pneumoniae Isolate.
AB  - Plasmid pKP12226 was extracted and analyzed from a CTX-M-15-producing Klebsiella
      pneumoniae sequence type 11 (ST11) isolate collected in South Korea. The plasmid
      represents chimeric characteristics consisting of a pIP1206-like backbone and
      lysogenized phage P1-like sequences. It bears a resistance region that includes
      resistance genes to several antibiotics and is different from previously
      characterized plasmids from South Korea bearing blaCTX-M-15. It may have resulted
      from recombination between an Escherichia coli plasmid backbone, a blaCTX-M-15
      bearing resistance region, and lysogenized phage P1-like sequences. 

PMID- 26195514
TI  - Antimicrobial Activity of Fosfomycin-Tobramycin Combination against Pseudomonas
      aeruginosa Isolates Assessed by Time-Kill Assays and Mutant Prevention
      Concentrations.
AB  - The antibacterial activity of fosfomycin-tobramycin combination was studied by
      time-kill assay in eight Pseudomonas aeruginosa clinical isolates belonging to
      the fosfomycin wild-type population (MIC = 64 MUg/ml) but with different
      tobramycin susceptibilities (MIC range, 1 to 64 MUg/ml). The mutant prevention
      concentration (MPC) and mutant selection window (MSW) were determined in five of
      these strains (tobramycin MIC range, 1 to 64 MUg/ml) in aerobic and anaerobic
      conditions simulating environments that are present in biofilm-mediated
      infections. Fosfomycin-tobramycin was synergistic and bactericidal for the
      isolates with mutations in the mexZ repressor gene, with a tobramycin MIC of 4
      MUg/ml. This effect was not observed in strains displaying tobramycin MICs of 1
      to 2 MUg/ml due to the strong bactericidal effect of tobramycin alone. Fosfomycin
      presented higher MPC values (range, 2,048 to >2,048 MUg/ml) in aerobic and
      anaerobic conditions than did tobramycin (range, 16 to 256 MUg/ml).
      Interestingly, the association rendered narrow or even null MSWs in the two
      conditions. However, for isolates with high-level tobramycin resistance that
      harbored aminoglycoside nucleotidyltransferases, time-kill assays showed no
      synergy, with wide MSWs in the two environments. glpT gene mutations responsible
      for fosfomycin resistance in P. aeruginosa were determined in fosfomycin
      susceptible wild-type strains and mutant derivatives recovered from MPC studies.
      All mutant derivatives had changes in the GlpT amino acid sequence, which
      resulted in a truncated permease responsible for fosfomycin resistance. These
      results suggest that fosfomycin-tobramycin can be an alternative for infections
      due to P. aeruginosa since it has demonstrated synergistic and bactericidal
      activity in susceptible isolates and those with low-level tobramycin resistance.
      It also prevents the emergence of resistant mutants in either aerobic or
      anaerobic environments. 

PMID- 26195515
TI  - Plasma Tenofovir, Emtricitabine, and Rilpivirine and Intracellular Tenofovir
      Diphosphate and Emtricitabine Triphosphate Pharmacokinetics following Drug Intake
      Cessation.
AB  - Pharmacokinetic (PK) data describing a prolonged time course of antiretrovirals
      in plasma and peripheral blood mononuclear cells (PBMCs) are important for
      understanding and managing late or missed doses and to assess the appropriateness
      of compounds for preexposure prophylaxis (PrEP). This study aimed to evaluate the
      PK of coformulated tenofovir disoproxil fumarate (DF), emtricitabine, and
      rilpivirine in plasma and of the intracellular (IC) anabolites tenofovir
      diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) in healthy
      volunteers up to 9 days after drug cessation. Individuals received daily
      tenofovir DF-emtricitabine-rilpivirine (245/200/25 mg) for 14 days. Drug intake
      was stopped, and serial sampling occurred prior to the final dose and up to 216 h
      (9 days) after stopping drug intake. Concentrations were quantified and PK
      parameters calculated. Eighteen volunteers completed the study. The terminal
      elimination plasma half-lives for tenofovir and emtricitabine over 216 h
      (geometric mean [90% confidence interval]) were higher than those seen over 0 to
      24 h (for tenofovir, 31 h [27 to 40 h] versus 13.3 h [12.5 to 15.1 h]; for
      emtricitabine, 41 h [36 to 54 h] versus 6.4 h (5.9 to 7.6 h]). Model-predicted IC
      half-lives (0 to 168 h) were 116 h (TFV-DP) and 37 h (FTC-TP). The plasma
      rilpivirine concentration at 216 h was 4.5 ng/ml (4.2 to 6.2 ng/ml), and half
      lives over 0 to 216 h and 0 to 24 h were 47 h (41 to 59 h) and 35 h (28 to 46 h),
      respectively. These data contribute to our understanding of drug behavior
      following treatment interruption; however, adherence to therapy should be
      promoted. Validated plasma and IC target concentrations are necessary to allow
      interpretation with respect to sustained virus suppression or HIV prevention.
      (The trial was conducted in accordance with the Declaration of Helsinki [EudraCT
      2012-002781-13].). 

PMID- 26195516
TI  - Antibiotic Susceptibility and Sequence Type Distribution of Ureaplasma Species
      Isolated from Genital Samples in Switzerland.
AB  - Antibiotic resistance in Ureaplasma urealyticum/Ureaplasma parvum and Mycoplasma
      hominis is an issue of increasing importance. However, data regarding the
      susceptibility and, more importantly, the clonality of these organisms are
      limited. We analyzed 140 genital samples obtained in Bern, Switzerland, in 2014.
      Identification and antimicrobial susceptibility tests were performed by using the
      Mycoplasma IST 2 kit and sequencing of 16S rRNA genes. MICs for ciprofloxacin and
      azithromycin were obtained in broth microdilution assays. Clonality was analyzed
      with PCR-based subtyping and multilocus sequence typing (MLST), whereas quinolone
      resistance and macrolide resistance were studied by sequencing gyrA, gyrB, parC,
      and parE genes, as well as 23S rRNA genes and genes encoding L4/L22 ribosomal
      proteins. A total of 103 samples were confirmed as positive for U. urealyticum/U.
      parvum, whereas 21 were positive for both U. urealyticum/U. parvum and M.
      hominis. According to the IST 2 kit, the rates of nonsusceptibility were highest
      for ciprofloxacin (19.4%) and ofloxacin (9.7%), whereas low rates were observed
      for clarithromycin (4.9%), erythromycin (1.9%), and azithromycin (1%). However,
      inconsistent results between microdilution and IST 2 kit assays were recorded.
      Various sequence types (STs) observed previously in China (ST1, ST2, ST4, ST9,
      ST22, and ST47), as well as eight novel lineages, were detected. Only some
      quinolone-resistant isolates had amino acid substitutions in ParC (Ser83Leu in U.
      parvum of serovar 6) and ParE (Val417Thr in U. parvum of serovar 1 and the novel
      Thr417Val substitution in U. urealyticum). Isolates with mutations in 23S rRNA or
      substitutions in L4/L22 were not detected. This is the first study analyzing the
      susceptibility of U. urealyticum/U. parvum isolates in Switzerland and the
      clonality outside China. Resistance rates were low compared to those in other
      countries. We hypothesize that some hyperepidemic STs spread worldwide via sexual
      intercourse. Large combined microbiological and clinical studies should address
      this important issue. 

PMID- 26195517
TI  - Genomic and Functional Portrait of a Highly Virulent, CTX-M-15-Producing H30-Rx
      Subclone of Escherichia coli Sequence Type 131.
AB  - Escherichia coli sequence type 131 (ST131) is a pandemic clone associated with
      multidrug-resistant, extraintestinal infections, attributable to the presence of
      the CTX-M-15 extended-spectrum beta-lactamase gene and mutations entailing
      fluoroquinolone resistance. Studies on subclones within E. coli ST131 are
      critically required for targeting and implementation of successful control
      efforts. Our study comprehensively analyzed the genomic and functional attributes
      of the H30-Rx subclonal strains NA097 and NA114, belonging to the ST131 lineage.
      We carried out whole-genome sequencing, comparative analysis, phenotypic
      virulence assays, and profiling of the antibacterial responses of THP1 cells
      infected with these subclones. Phylogenomic analysis suggested that the strains
      were clonal in nature and confined entirely to a single clade. Comparative
      genomic analysis revealed that the virulence and resistance repertoires were
      comparable among the H30-Rx ST131 strains except for the commensal ST131 strain
      SE15. Similarly, seven phage-specific regions were found to be strongly
      associated with the H30-Rx strains but were largely absent in the genome of SE15.
      Phenotypic analysis confirmed the virulence and resistance similarities between
      the two strains. However, NA097 was found to be more robust than NA114 in terms
      of virulence gene carriage (dra operon), invasion ability (P < 0.05), and
      antimicrobial resistance (streptomycin resistance). RT(2) gene expression
      profiling revealed generic upregulation of key proinflammatory responses in THP1
      cells, irrespective of ST131 lineage status. In conclusion, our study provides
      comprehensive, genome-inferred insights into the biology and immunological
      properties of ST131 strains and suggests clonal diversification of genomic and
      phenotypic features within the H30-Rx subclone of E. coli ST131. 

PMID- 26195518
TI  - In Vitro Activity of AZD0914, a Novel Bacterial DNA Gyrase/Topoisomerase IV
      Inhibitor, against Clinically Relevant Gram-Positive and Fastidious Gram-Negative
      Pathogens.
AB  - AZD0914, a new spiropyrimidinetrione bacterial DNA gyrase inhibitor with a novel
      mode of inhibition, has activity against bacterial species commonly cultured from
      patient infection specimens, including fluoroquinolone-resistant isolates. This
      study assessed the in vitro activity of AZD0914 against key Gram-positive and
      fastidious Gram-negative clinical isolates collected globally in 2013. AZD0914
      demonstrated potent activity, with MIC90s for AZD0914 of 0.25 mg/liter against
      Staphylococcus aureus (n = 11,680), coagulase-negative staphylococci (n = 1,923),
      streptococci (n = 4,380), and Moraxella catarrhalis (n = 145), 0.5 mg/liter
      against Staphylococcus lugdunensis (n = 120) and Haemophilus influenzae (n =
      352), 1 mg/liter against Enterococcus faecalis (n = 1,241), and 2 mg/liter
      against Haemophilus parainfluenzae (n = 70). The activity against Enterococcus
      faecium was more limited (MIC90, 8 mg/liter). The spectrum and potency of AZD0914
      included fluoroquinolone-resistant isolates in each species group, including
      methicillin-resistant staphylococci, penicillin-resistant streptococci,
      vancomycin-resistant enterococci, beta-lactamase-producing Haemophilus spp., and
      M. catarrhalis. Based on these in vitro findings, AZD0914 warrants further
      investigation for its utility against a variety of Gram-positive and fastidious
      Gram-negative bacterial species. 

PMID- 26195519
TI  - A Toll-Like Receptor 5 Agonist Improves the Efficacy of Antibiotics in Treatment
      of Primary and Influenza Virus-Associated Pneumococcal Mouse Infections.
AB  - Prophylactic intranasal administration of the Toll-like receptor 5 (TLR5) agonist
      flagellin protects mice against respiratory pathogenic bacteria. We hypothesized
      that TLR5-mediated stimulation of lung immunity might improve the therapeutic
      index of antibiotics for the treatment of Streptococcus pneumoniae respiratory
      infections in mice. Intranasal administration of flagellin was combined with
      either oral administration of amoxicillin or intraperitoneal injection of
      trimethoprim-sulfamethoxazole to treat S. pneumoniae-infected animals. Compared
      with standalone treatments, the combination of antibiotic and flagellin resulted
      in a lower bacterial load in the lungs and greater protection against S.
      pneumoniae dissemination and was associated with an early increase in neutrophil
      infiltration in the airways. The antibiotic-flagellin combination treatment was,
      however, not associated with any exacerbation of inflammation. Moreover,
      combination treatment was more efficacious than standalone antibiotic treatments
      in the context of post-influenza virus pneumococcal infection. Lastly, TLR5
      signaling was shown to be mandatory for the efficacy of the combined
      antibacterial therapy. This report is the first to show that combining antibiotic
      treatment with the stimulation of mucosal innate immunity is a potent
      antibacterial strategy against pneumonia. 

PMID- 26195520
TI  - Effective Antibiofilm Polyketides against Staphylococcus aureus from the
      Pyranonaphthoquinone Biosynthetic Pathways of Streptomyces Species.
AB  - Streptomyces bacteria are renowned for their ability to produce bioactive
      secondary metabolites. Recently, synthetic biology has enabled the production of
      intermediates and shunt products, which may have altered biological activities
      compared to the end products of the pathways. Here, we have evaluated the
      potential of recently isolated alnumycins and other closely related
      pyranonaphthoquinone (PNQ) polyketides against Staphylococcus aureus biofilms.
      The antimicrobial potency of the compounds against planktonic cells and biofilms
      was determined by redox dye-based viability staining, and the antibiofilm
      efficacy of the compounds was confirmed by viable counting. A novel
      antistaphylococcal polyketide, alnumycin D, was identified. Unexpectedly, the C
      ribosylated pathway shunt product alnumycin D was more active against planktonic
      and biofilm cells than the pathway end product alnumycin A, where a ribose unit
      has been converted into a dioxane moiety. The evaluation of the antibiofilm
      potential of other alnumycins revealed that the presence of the ribose moiety in
      pyranose form is essential for high activity against preformed biofilms.
      Furthermore, the antibiofilm potential of other closely related PNQ polyketides
      was examined. Based on their previously reported activity against planktonic S.
      aureus cells, granaticin B, kalafungin, and medermycin were also selected for
      testing, and among them, granaticin B was found to be the most potent against
      preformed biofilms. The most active antibiofilm PNQs, alnumycin D and granaticin
      B, share several structural features that may be important for their antibiofilm
      activity. They are uncharged, glycosylated, and also contain a similar
      oxygenation pattern of the lateral naphthoquinone ring. These findings highlight
      the potential of antibiotic biosynthetic pathways as a source of effective
      antibiofilm compounds. 

PMID- 26195521
TI  - Robust Algorithm for Systematic Classification of Malaria Late Treatment Failures
      as Recrudescence or Reinfection Using Microsatellite Genotyping.
AB  - Routine therapeutic efficacy monitoring to measure the response to antimalarial
      treatment is a cornerstone of malaria control. To correctly measure drug
      efficacy, therapeutic efficacy studies require genotyping parasites from late
      treatment failures to differentiate between recrudescent infections and
      reinfections. However, there is a lack of statistical methods to systematically
      classify late treatment failures from genotyping data. A Bayesian algorithm was
      developed to estimate the posterior probability of late treatment failure being
      the result of a recrudescent infection from microsatellite genotyping data. The
      algorithm was implemented using a Monte Carlo Markov chain approach and was used
      to classify late treatment failures using published microsatellite data from
      therapeutic efficacy studies in Ethiopia and Angola. The algorithm classified 85%
      of the Ethiopian and 95% of the Angolan late treatment failures as either likely
      reinfection or likely recrudescence, defined as a posterior probability of
      recrudescence of <0.1 or >0.9, respectively. The adjusted efficacies calculated
      using the new algorithm differed from efficacies estimated using commonly used
      methods for differentiating recrudescence from reinfection. In a high
      transmission setting such as Angola, as few as 15 samples needed to be genotyped
      in order to have enough power to correctly classify treatment failures. Analysis
      of microsatellite genotyping data for differentiating between recrudescence and
      reinfection benefits from an approach that both systematically classifies late
      treatment failures and estimates the uncertainty of these classifications.
      Researchers analyzing genotyping data from antimalarial therapeutic efficacy
      monitoring are urged to publish their raw genetic data and to estimate the
      uncertainty around their classification. 

PMID- 26195522
TI  - Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium
      difficile Infection Treated with Metronidazole.
AB  - Consensus on the optimal treatment of Clostridium difficile infection (CDI) is
      rapidly changing. Treatment with metronidazole has been associated with increased
      clinical failure rates; however, the reasons for this are unclear. The purpose of
      this study was to assess age-related treatment response rates in hospitalized
      patients with CDI treated with metronidazole. This was a retrospective,
      multicenter cohort study of hospitalized patients with CDI. Patients were
      assessed for refractory CDI, defined as persistent diarrhea after 7 days of
      metronidazole therapy, and stratified by age and clinical characteristics. A
      total of 242 individuals, aged 60 +/- 18 years (Charlson comorbidity index, 3.8
      +/- 2.4; Horn's index, 1.7 +/- 1.0) were included. One hundred twenty-eight
      patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a
      percentage that increased from 22% to 28% and to 37% for patients aged less than
      50 years, for patients from 50 to 70 years, and for patients aged >70 years,
      respectively (P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR],
      2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR,
      2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR,
      2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors
      of refractory CDI. Age was not identified as an independent risk factor for
      refractory CDI. Therefore, hospitalized elderly patients with CDI treated with
      metronidazole had increased refractory CDI rates likely due to increased
      underlying severity of illness, severity of CDI, and concomitant antibiotic use.
      These results may help identify patients that may benefit from alternative C.
      difficile treatments other than metronidazole. 

PMID- 26195523
TI  - Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant
      Clinical Isolates of Plasmodium falciparum and Plasmodium vivax.
AB  - The 4-aminoquinoline naphthoquine (NQ) and the thiazine dye methylene blue (MB)
      have potent in vitro efficacies against Plasmodium falciparum, but susceptibility
      data for P. vivax are limited. The species- and stage-specific ex vivo activities
      of NQ and MB were assessed using a modified schizont maturation assay on clinical
      field isolates from Papua, Indonesia, where multidrug-resistant P. falciparum and
      P. vivax are prevalent. Both compounds were highly active against P. falciparum
      (median [range] 50% inhibitory concentration [IC50]: NQ, 8.0 nM [2.6 to 71.8 nM];
      and MB, 1.6 nM [0.2 to 7.0 nM]) and P. vivax (NQ, 7.8 nM [1.5 to 34.2 nM]; and
      MB, 1.2 nM [0.4 to 4.3 nM]). Stage-specific drug susceptibility assays revealed
      significantly greater IC50s in parasites exposed at the trophozoite stage than at
      the ring stage for NQ in P. falciparum (26.5 versus 5.1 nM, P = 0.021) and P.
      vivax (341.6 versus 6.5 nM, P = 0.021) and for MB in P. vivax (10.1 versus 1.6
      nM, P = 0.010). The excellent ex vivo activities of NQ and MB against both P.
      falciparum and P. vivax highlight their potential utility for the treatment of
      multidrug-resistant malaria in areas where both species are endemic. 

PMID- 26195524
TI  - Delicate Metabolic Control and Coordinated Stress Response Critically Determine
      Antifungal Tolerance of Candida albicans Biofilm Persisters.
AB  - Candida infection has emerged as a critical health care burden worldwide, owing
      to the formation of robust biofilms against common antifungals. Recent evidence
      shows that multidrug-tolerant persisters critically account for biofilm
      recalcitrance, but their underlying biological mechanisms are poorly understood.
      Here, we first investigated the phenotypic characteristics of Candida biofilm
      persisters under consecutive harsh treatments of amphotericin B. The prolonged
      treatments effectively killed the majority of the cells of biofilms derived from
      representative strains of Candida albicans, Candida glabrata, and Candida
      tropicalis but failed to eradicate a small fraction of persisters. Next, we
      explored the tolerance mechanisms of the persisters through an investigation of
      the proteomic profiles of C. albicans biofilm persister fractions by liquid
      chromatography-tandem mass spectrometry. The C. albicans biofilm persisters
      displayed a specific proteomic signature, with an array of 205 differentially
      expressed proteins. The crucial enzymes involved in glycolysis, the tricarboxylic
      acid cycle, and protein synthesis were markedly downregulated, indicating that
      major metabolic activities are subdued in the persisters. It is noteworthy that
      certain metabolic pathways, such as the glyoxylate cycle, were able to be
      activated with significantly increased levels of isocitrate lyase and malate
      synthase. Moreover, a number of important proteins responsible for Candida
      growth, virulence, and the stress response were greatly upregulated.
      Interestingly, the persisters were tolerant to oxidative stress, despite highly
      induced intracellular superoxide. The current findings suggest that delicate
      metabolic control and a coordinated stress response may play a crucial role in
      mediating the survival and antifungal tolerance of Candida biofilm persisters. 

PMID- 26195525
TI  - Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk
      Factors and Comparison of the Product from Two Different Manufacturers.
AB  - Benznidazole is considered the first-line treatment option against Chagas
      disease. The major drawback of benznidazole is its toxicity profile. The main
      objectives of this study were to describe the adverse events (AEs) in patients
      with chronic Chagas disease treated with benznidazole, determine the risk factors
      involved and compare the toxic profiles of two different preparations of the drug
      from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease
      in a 5-year period, and of these 472 were treated with benznidazole. A high
      proportion of patients (n = 360 [76%]) suffered AEs, the most frequent being
      those related to hypersensitivity (52.9% of patients), headache (12.5%), and
      epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued.
      Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%, P
      = 0.001) and were subject to higher levels of hypersensitivity-related events.
      Dermatological events, digestive tract manifestations, and general symptoms had a
      greater likelihood to appear around day 10 and neurological AEs around day 40
      after starting treatment. With respect to liver function and hematological tests,
      the majority of patients did not suffer significant perturbation of liver enzymes
      or altered blood cell counts. However, 14 patients suffered from neutropenia, and
      14 patients had aminotransferase levels that were more than four times the upper
      limit of the normal range. Patients treated with the ELEA benznidazole product
      experienced more arthromyalgia, neutropenia, and neurological disorders (mainly
      paresthesias) than those treated with the Roche product. Both drug products
      resulted in approximately the same percentage of permanent withdrawals. 

PMID- 26195526
TI  - Carriage of Escherichia coli Producing CTX-M-Type Extended-Spectrum beta
      Lactamase in Healthy Vietnamese Individuals.
AB  - Healthy carriage of CTX-M-type extended-spectrum beta-lactamase (ESBL)-producing
      Escherichia coli was examined by thrice collecting fecal samples from the same
      199 healthy Vietnamese subjects every 6 months. Using pulsed-field gel
      electrophoresis (PFGE), identical PFGE patterns throughout the three samplings
      were not observed, although prevalence of E. coli in the subjects was around 50%
      in the three samplings. Our results suggested a short carriage period of the CTX
      M-type ESBL-producing E. coli in healthy Vietnamese subjects. 

PMID- 26195528
TI  - Differential Effects of Penicillin Binding Protein Deletion on the Susceptibility
      of Enterococcus faecium to Cationic Peptide Antibiotics.
AB  - Beta-lactam antibiotics sensitize Enterococcus faecium to killing by endogenous
      antimicrobial peptides (AMPs) of the innate immune system and daptomycin through
      mechanisms yet to be elucidated. It has been speculated that beta-lactam
      inactivation of select E. faecium penicillin binding proteins (PBPs) may play a
      pivotal role in this sensitization process. To characterize the specific PBP
      inactivation that may be responsible for these phenotypes, we utilized a
      previously characterized set of E. faecium PBP knockout mutants to determine the
      effects of such mutations on the activity of daptomycin and the AMP human
      cathelicidin (LL-37). Enhanced susceptibility to daptomycin was dependent more on
      a cumulative effect of multiple PBP deletions than on inactivation of any single
      specific PBP. Selective knockout of PBPZ rendered E. faecium more vulnerable to
      killing by both recombinant LL-37 and human neutrophils, which produce the
      antimicrobial peptide in high quantities. Pharmacotherapy targeting multiple PBPs
      may be used as adjunctive therapy with daptomycin to treat difficult E. faecium
      infections. 

PMID- 26195527
TI  - The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.
AB  - The protozoan parasite Trypanosoma brucei causes human African trypanosomiasis,
      or sleeping sickness, a neglected tropical disease that requires new, safer, and
      more effective treatments. Repurposing oral drugs could reduce both the time and
      cost involved in sleeping sickness drug discovery. Tafenoquine (TFQ) is an oral
      antimalarial drug belonging to the 8-aminoquinoline family which is currently in
      clinical phase III. We show here that TFQ efficiently kills different T. brucei
      spp. in the submicromolar concentration range. Our results suggest that TFQ
      accumulates into acidic compartments and induces a necrotic process involving
      cell membrane disintegration and loss of cytoplasmic content, leading to parasite
      death. Cell lysis is preceded by a wide and multitarget drug action, affecting
      the lysosome, mitochondria, and acidocalcisomes and inducing a depolarization of
      the mitochondrial membrane potential, elevation of intracellular Ca(2+), and
      production of reactive oxygen species. This is the first report of an 8
      aminoquinoline demonstrating significant in vitro activity against T. brucei. 

PMID- 26195529
TI  - Subinhibitory Doses of Aminoglycoside Antibiotics Induce Changes in the Phenotype
      of Mycobacterium abscessus.
AB  - Subinhibitory doses of antibiotics have been shown to cause changes in bacterial
      morphology, adherence ability, and resistance to antibiotics. In this study, the
      effects of subinhibitory doses of aminoglycoside antibiotics on Mycobacterium
      abscessus were investigated. The treatment of M. abscessus cells with
      subinhibitory doses of amikacin was found to change their colony from a smooth to
      a rough morphotype and increase their ability to adhere to a polyvinylchloride
      plate, aggregate in culture, and resist phagocytosis and killing by macrophages.
      M. abscessus cells treated with a subinhibitory dose of amikacin also became more
      potent in Toll-like receptor 2 (TLR-2) stimulation, leading to increased tumor
      necrosis factor alpha (TNF-alpha) production by macrophages. The MAB_3508c gene
      was shown to play a role in mediating these phenotypic changes, as its expression
      in M. abscessus cells was increased when they were treated with a subinhibitory
      dose of amikacin. In addition, overexpression of MAB_3508c in M. abscessus cells
      caused changes similar to those induced by subinhibitory doses of amikacin,
      including a switch from smooth to rough colony morphology, increased ability to
      aggregate in liquid culture, decreased motility, and increased resistance to
      killing by macrophages. These findings suggest the importance of using sufficient
      doses of antibiotics for the treatment of M. abscessus infections. 

PMID- 26195531
TI  - Addressing Vaccine Hesitancy With Values.

PMID- 26195530
TI  - Epidemiologic Correlates of Pyrazinamide-Resistant Mycobacterium tuberculosis in
      New York City.
AB  - Pyrazinamide (PZA) has important sterilizing activity in tuberculosis (TB)
      chemotherapy. We describe trends, risk factors, and molecular epidemiology
      associated with PZA-resistant (PZA(r)) Mycobacterium tuberculosis in New York
      City (NYC). From 2001 to 2008, all incident culture-positive TB cases reported by
      the NYC Department of Health and Mental Hygiene (DOHMH) were genotyped by IS6110
      based restriction fragment length polymorphism and spoligotype. Multidrug
      resistant (MDR) isolates underwent DNA sequencing of resistance-determining
      regions of pncA, rpoB, katG, and fabG1. Demographic and clinical information were
      extracted from the NYC DOHMH TB registry. During this period, PZA(r) doubled
      (1.6% to 3.6%) overall, accounting for 44% (70/159) of the MDR population and
      1.4% (75/5511) of the non-MDR population. Molecular genotyping revealed strong
      microbial phylogenetic associations with PZA(r). Clustered isolates and those
      from acid-fast bacillus (AFB) smear-positive cases had 2.7 (95% confidence
      interval [CI] = 1.71 to 4.36) and 2.0 (95% CI = 1.19 to 3.43) times higher odds
      of being PZA(r), respectively, indicating a strong likelihood of recent
      transmission. Among the MDR population, PZA(r) was acquired somewhat more
      frequently via primary transmission than by independent pathways. Our molecular
      analysis also revealed that several historic M. tuberculosis strains responsible
      for MDR TB outbreaks in the early 1990s were continuing to circulate in NYC. We
      conclude that the increasing incidence of PZA(r), with clear microbial risk
      factors, underscores the importance of routine PZA drug susceptibility testing
      and M. tuberculosis genotyping for the identification, control, and prevention of
      increasingly resistant organisms. 

PMID- 26195532
TI  - Tip of the Iceberg: Understanding the Unintended Consequences of Antibiotics.

PMID- 26195533
TI  - Antibiotic Exposure and Juvenile Idiopathic Arthritis: A Case-Control Study.
AB  - BACKGROUND AND OBJECTIVE: Recent evidence has linked childhood antibiotic use and
      microbiome disturbance to autoimmune conditions. This study tested the hypothesis
      that antibiotic exposure was associated with newly diagnosed juvenile idiopathic
      arthritis (JIA). METHODS: We performed a nested case-control study in a
      population-representative medical records database from the United Kingdom.
      Children with newly diagnosed JIA were compared with age- and gender-matched
      control subjects randomly selected from general practices containing at least 1
      case, excluding those with inflammatory bowel disease, immunodeficiency, or other
      systemic rheumatic diseases. Conditional logistic regression was used to examine
      the association between antibacterial antibiotics (including number of antibiotic
      courses and timing) and JIA after adjusting for significant confounders. RESULTS:
      Any antibiotic exposure was associated with an increased rate of developing JIA
      (adjusted odds ratio: 2.1 [95% confidence interval: 1.2-3.5]). This relationship
      was dose dependent (adjusted odds ratio over 5 antibiotic courses: 3.0 [95%
      confidence interval: 1.6-5.6]), strongest for exposures within 1 year of
      diagnosis, and did not substantively change when adjusting for number or type of
      infections. In contrast, nonbacterial antimicrobial agents (eg, antifungal,
      antiviral) were not associated with JIA. In addition, antibiotic-treated upper
      respiratory tract infections were more strongly associated with JIA than
      untreated upper respiratory tract infections. CONCLUSIONS: Antibiotics were
      associated with newly diagnosed JIA in a dose- and time-dependent fashion in a
      large pediatric population. Antibiotic exposure may play a role in JIA
      pathogenesis, perhaps mediated through alterations in the microbiome.

PMID- 26195534
TI  - Decision-Making and the Barriers to Judicious Antibiotic Use.

PMID- 26195535
TI  - Use of Serum Bicarbonate to Substitute for Venous pH in New-Onset Diabetes.
AB  - OBJECTIVE: To investigate whether serum bicarbonate (HCO3) levels can be used to
      accurately diagnose diabetic ketoacidosis (DKA) and classify its severity in
      children with new-onset diabetes mellitus (NODM). METHODS: Retrospective study of
      all patients with NODM presenting to Boston Children's Hospital from October 1,
      2007, to July 1, 2013. DKA was defined as blood glucose >=200 mg/dL, venous pH
      (vpH) <7.3, and urine ketones >=2+, and severe DKA as vpH <7.1. Linear regression
      was used to assess serum HCO3 as a predictor of vpH, and logistic regression to
      evaluate serum HCO3 as a predictor of DKA and severe DKA. RESULTS: Of 690 study
      cohort subjects (47% girls, age 10.8 +/- 4.3 years, 76.7% white), 19.4% presented
      with DKA. The relationship between serum HCO3 and vpH was log-linear (r = 0.87,
      95% CI 0.85-0.89, P < .001). HCO3 predicted vpH (R(2) 0.75, P < .001) using the
      formula vpH = 6.81301 + (0.17823*ln[HCO3]) and DKA and severe DKA (c-statistic
      0.97 [95% CI 0.96-0.99, P < .001] and 0.99 [95% CI 0.991-0.999, P < .001],
      respectively). HCO3 cutoffs of <18 and <8 mmol/L had sensitivities of 91.8% and
      95.2%, and specificities of 91.7% and 96.7%, respectively, to diagnose DKA and
      severe DKA. Findings were similar in a validation cohort of 197 subjects.
      CONCLUSIONS: Serum HCO3 concentration alone can substitute for vpH to diagnose
      DKA and classify severity in children with NODM. It is suggested as an
      alternative to reliance on vpH, especially in settings in which access to vpH
      measurement is limited.

PMID- 26195536
TI  - Choosing Wisely in Newborn Medicine: Five Opportunities to Increase Value.
AB  - BACKGROUND: The use of unnecessary tests and treatments contributes to health
      care waste. The "Choosing Wisely" campaign charges medical societies with
      identifying such items. This report describes the identification of 5 tests and
      treatments in newborn medicine. METHODS: A national survey identified candidate
      tests and treatments. An expert panel of 51 individuals representing 28 perinatal
      care organizations narrowed the list over 3 rounds of a modified Delphi process.
      In the final round, the panel was provided with Grading of Recommendation,
      Assessment, Development and Evaluation (GRADE) literature summaries of the top 12
      tests and treatments. RESULTS: A total of 1648 candidate tests and 1222
      treatments were suggested by 1047 survey respondents. After 3 Delphi rounds, the
      expert panel achieved consensus on the following top 5 items: (1) avoid routine
      use of antireflux medications for treatment of symptomatic gastroesophageal
      reflux disease or for treatment of apnea and desaturation in preterm infants, (2)
      avoid routine continuation of antibiotic therapy beyond 48 hours for initially
      asymptomatic infants without evidence of bacterial infection, (3) avoid routine
      use of pneumograms for predischarge assessment of ongoing and/or prolonged apnea
      of prematurity, (4) avoid routine daily chest radiographs without an indication
      for intubated infants, and (5) avoid routine screening term-equivalent or
      discharge brain MRIs in preterm infants. CONCLUSIONS: The Choosing Wisely Top
      Five for newborn medicine highlights tests and treatments that cannot be
      adequately justified on the basis of efficacy, safety, or cost. This list serves
      as a starting point for quality improvement efforts to optimize both clinical
      outcomes and resource utilization in newborn care.

PMID- 26195537
TI  - An Adolescent Case of Citrin Deficiency With Severe Anorexia Mimicking Anorexia
      Nervosa.
AB  - We report a 12-year-old female citrin-deficient patient presenting with severe
      anorexia and body weight loss, mimicking the restricting type of anorexia nervosa
      (AN). She showed normal development until age 10 years when she started to play
      volleyball at school. She then became gradually anorexic, and her growth was
      stunted. At age 12, she was admitted to hospital because of severe anorexia and
      thinness. She was first thought to have AN, and drip infusion of glucose solution
      and high-calorie drinks were given, but her condition deteriorated further. She
      had a history of neonatal hepatitis and was therefore suspected to have citrin
      deficiency (CD). Genetic analysis of SLC25A13 revealed that she was compound
      heterozygous for 851del4 and IVS16ins3kb, and a diagnosis of CD was made. A low
      carbohydrate diet with oral intake of arginine and ursodeoxycholic acid was
      started, and her condition gradually improved. The clinical features in our
      patient were similar to those of AN, and therefore AN may also be an important
      clinical sign in adolescent patients with CD. 

PMID- 26195538
TI  - Prevalence of and Risk Factors for Intracranial Abnormalities in Unprovoked
      Seizures.
AB  - BACKGROUND AND OBJECTIVES: Prospective data are lacking to determine which
      children might benefit from prompt neuroimaging after unprovoked seizures. We
      aimed to determine the prevalence of, and risk factors for, relevant intracranial
      abnormalities in children with first, unprovoked seizures. METHODS: We conducted
      a 6-center prospective study in children aged >28 days to 18 years with seemingly
      unprovoked seizures. Emergency department (ED) clinicians documented clinical
      findings on a standardized form. Our main outcome was the presence of a
      clinically relevant intracranial abnormality on computed tomography (CT) or MRI,
      defined as those that might change management, either emergently, urgently, or
      nonurgently. RESULTS: We enrolled 475 of 625 (76%) eligible patients. Of 354
      patients for whom cranial MRI or CT scans were obtained in the ED or within 4
      months of the ED visit, 40 (11.3%; 95% confidence interval [CI]: 8.0-14.6%) had
      clinically relevant intracranial abnormalities, with 3 (0.8%; 95% CI: 0.1-1.8%)
      having emergent/urgent abnormalities. On logistic regression analysis, a high
      risk past medical history (adjusted odds ratio: 9.2; 95% CI: 2.4-35.7) and any
      focal aspect to the seizure (odds ratio: 2.5; 95% CI: 1.2-5.3) were independently
      associated with clinically relevant abnormalities. CONCLUSIONS: Clinically
      relevant intracranial abnormalities occur in 11% of children with first,
      unprovoked seizures. Emergent/urgent abnormalities, however, occur in <1%,
      suggesting that most children do not require neuroimaging in the ED. Findings on
      patient history and physical examination identify patients at higher risk of
      relevant abnormalities.

PMID- 26195539
TI  - Prevalence of Parental Misconceptions About Antibiotic Use.
AB  - BACKGROUND: Differences in antibiotic knowledge and attitudes between parents of
      Medicaid-insured and commercially insured children have been previously reported.
      It is unknown whether understanding has improved and whether previously
      identified differences persist. METHODS: A total of 1500 Massachusetts parents
      with a child <6 years old insured by a Medicaid managed care or commercial health
      plan were surveyed in spring 2013. We examined antibiotic-related knowledge and
      attitudes by using chi(2) tests. Multivariable modeling was used to assess
      current sociodemographic predictors of knowledge and evaluate changes in
      predictors from a similar survey in 2000. RESULTS: Medicaid-insured parents in
      2013 (n = 345) were younger, were less likely to be white, and had less education
      than those commercially insured (n = 353), P < .01. Fewer Medicaid-insured
      parents answered questions correctly except for one related to bronchitis, for
      which there was no difference (15% Medicaid vs 16% commercial, P < .66). More
      parents understood that green nasal discharge did not require antibiotics in 2013
      compared with 2000, but this increase was smaller among Medicaid-insured (32% vs
      22% P = .02) than commercially insured (49% vs 23%, P < .01) parents. Medicaid
      insured parents were more likely to request unnecessary antibiotics in 2013 (P <
      .01). Multivariable models for predictors of knowledge or attitudes demonstrated
      complex relationships between insurance status and sociodemographic variables.
      CONCLUSIONS: Misconceptions about antibiotic use persist and continue to be more
      prevalent among parents of Medicaid-insured children. Improvement in
      understanding has been more pronounced in more advantaged populations. Tailored
      efforts for socioeconomically disadvantaged populations remain warranted to
      decrease parental drivers of unnecessary antibiotic prescribing.

PMID- 26195540
TI  - Trisomy 21 and Risk of Retinopathy of Prematurity.
AB  - BACKGROUND AND OBJECTIVES: Trisomy 21 is known to decrease the risk of several
      (nonocular) angiogenic-mediated diseases. The objective of this study was to
      determine whether trisomy 21 can also be shown to be significantly protective
      against ocular angiogenic-mediated disorders such as retinopathy of prematurity
      (ROP). METHODS: A retrospective analysis of deidentified data from the Pediatrix
      BabySteps Clinical Warehouse. This large repository of neonatal data is approved
      for use in research studies by the Western Institutional Review Board. The study
      population consisted of 99,080 infants with very low birth weights (BWs; BW <1500
      g), born between 1996 and 2013, cared for at >300 US NICUs, and who had been
      discharged alive from hospital. Statistical significance for unadjusted
      comparisons between groups was determined with Pearson's chi(2) test or Student's
      t test. Logistic regression models were used to calculate the odds of ROP (of any
      stage) and advanced ROP (stage 3 or greater) for infants with trisomy 21 compared
      with all other infants. RESULTS: The prevalence of trisomy 21 was 0.3% in the
      study population (321 of 99,080). After adjustment for BW, gestational age,
      oxygen exposure, and other potential confounders, there was an odds ratio of 0.6
      (95% confidence interval: 0.5-0.8) for ROP in infants with trisomy 21compared
      with other infants and an odds ratio of 0.4 (95% confidence interval: 0.1-0.9)
      for advanced-stage ROP. CONCLUSIONS: Trisomy 21 significantly decreases the odds
      for ROP in very low BW infant survivors. This study unmasks a potentially
      identifiable genetic component to ROP risk, paving the way for the development of
      a laboratory-based ROP screening tool.

PMID- 26195541
TI  - A Tailored Family-Based Obesity Intervention: A Randomized Trial.
AB  - OBJECTIVE: To determine whether a 2-year family-based intervention using frequent
      contact and limited expert involvement was effective in reducing excessive weight
      compared with usual care. METHODS: Two hundred and six overweight and obese (BMI
      >=85th percentile) children aged 4 to 8 years were randomized to usual care (UC)
      or tailored package (TP) sessions at university research rooms. UC families
      received personalized feedback and generalized advice regarding healthy
      lifestyles at baseline and 6 months. TP families attended a single
      multidisciplinary session to develop specific goals suitable for each family,
      then met with a mentor each month for 12 months, and every third month for
      another 12 months to discuss progress and provide support. Outcome measurements
      (anthropometry, questionnaires, dietary intake, accelerometry) were obtained at
      0, 12, and 24 months. RESULTS: BMI at 24 months was significantly lower in TP
      compared with UC children (difference, 95% confidence interval: -0.34, -0.65 to 
      0.02), as was BMI z score (-0.12, -0.20 to -0.04) and waist circumference (-1.5, 
      2.5 to -0.5 cm). TP children consumed more fruit and vegetables (P = .038) and
      fewer noncore foods (P = .020) than UC children, and fewer noncore foods were
      available in the home (P = .002). TP children were also more physically active (P
      = .035). No differences in parental feeding practices, parenting, quality of
      life, child sleep, or behavior were observed. CONCLUSIONS: Frequent, low-dose
      support was effective for reducing excessive weight in predominantly mild to
      moderately overweight children over a 2-year period. Such initiatives could
      feasibly be incorporated into primary care.

PMID- 26195542
TI  - The Development of a Pediatric Inpatient Experience of Care Measure: Child
      HCAHPS.
AB  - The Centers for Medicare and Medicaid Services (CMS) uses Adult Hospital Consumer
      Assessment of Healthcare Providers and Systems (Adult HCAHPS) scores for public
      reporting and pay-for-performance for most US hospitals, but no publicly
      available standardized survey of inpatient experience of care exists for
      pediatrics. To fill the gap, CMS and the Agency for Healthcare Research and
      Quality commissioned the development of a pediatric version (Child HCAHPS), a
      survey of parents/guardians of pediatric patients (<18 years old) who were
      recently hospitalized. This article describes the development of Child HCAHPS,
      which included an extensive review of the literature and quality measures, expert
      interviews, focus groups, cognitive testing, pilot testing of the draft survey, a
      national field test with 69 hospitals in 34 states, psychometric analysis, and
      end-user testing of the final survey. We conducted extensive validity and
      reliability testing to determine which items would be included in the final
      survey instrument and develop composite measures. We analyzed national field test
      data of 17,727 surveys collected in November 2012 to January 2014 from parents of
      recently hospitalized children. The final Child HCAHPS instrument has 62 items,
      including 39 patient experience items, 10 screeners, 12 demographic/descriptive
      items, and 1 open-ended item. The 39 experience items are categorized based on
      testing into 18 composite and single-item measures. Our composite and single-item
      measures demonstrated good to excellent hospital-level reliability at 300
      responses per hospital. Child HCAHPS was developed to be a publicly available
      standardized survey of pediatric inpatient experience of care. It can be used to
      benchmark pediatric inpatient experience across hospitals and assist in efforts
      to improve the quality of inpatient care.

PMID- 26195543
TI  - Home Foreclosure and Child Protective Services Involvement.
AB  - OBJECTIVE: We estimated associations between experiencing a home foreclosure
      filing and experiencing a child protective services (CPS) investigation or
      substantiation. METHODS: We linked a large sample drawn from administrative data
      on foreclosure filings, CPS involvement, and participation in a host of other
      public programs for >60,000 Wisconsin households over a 4-year period from 2008
      to 2011. Our empirical analyses used piecewise exponential survival models to
      estimate the risk of CPS involvement (investigation or substantiation) as a
      function of a home foreclosure filing and a set of individual and household
      characteristics. We fitted these models with and without the inclusion of
      propensity score weights. RESULTS: Households that experienced a foreclosure
      filing had a much higher probability of CPS involvement. This was true in the
      year before the filing as well as the year after the foreclosure filing. However,
      these associations were generally largest in the period before or shortly
      afterward. CONCLUSIONS: Experiencing a foreclosure filing is associated with
      increased CPS involvement. However, it is not clear that this association is
      driven by the foreclosure filing action itself. Rather, increased risk of CPS
      involvement is apparent during the process of moving toward the filing as well as
      the year or so after the filing, both of which are likely characterized by
      limited economic resources as well as by financial and other stress.

PMID- 26195544
TI  - Implementation of Postoperative Respiratory Care for Pediatric Orthopedic
      Patients.
AB  - BACKGROUND AND OBJECTIVES: At our institution, one-fifth of pediatric patients
      undergoing hip and spine surgery require prolonged oxygen supplementation, most
      likely due to postoperative atelectasis. Using quality improvement methodology,
      we aimed to implement an innovative postoperative respiratory care algorithm for
      hip and spine surgery patients, with a global aim of improving respiratory
      outcomes. METHODS: A multidisciplinary team developed a care algorithm that
      relied on an activated respiratory therapist (RT) and engagement of patients and
      families. The algorithm was implemented via multiple rapid tests of change.
      Process measures representing the beginning and end of the care algorithm were
      plotted on standard run charts. We evaluated the association of algorithm
      implementation with a primary outcome of prolonged (>10 hours) oxygen
      supplementation via a quasi-experimental design using Fisher's exact and t tests.
      RESULTS: The team successfully implemented the algorithm, with a reliability to
      process of 80%. Key interventions included education of RTs, a daily huddle, and
      implementation of automated orders. Among all hip and spine patients, algorithm
      implementation was associated with a small, non-statistically significant
      decrease in prolonged oxygen use (21% to 16%). Among patients with underlying
      chronic conditions, there was a significant decrease in prolonged oxygen use from
      22% to 6% after algorithm implementation (P = .04). CONCLUSIONS: We implemented
      an innovative respiratory care algorithm in hip and spine surgery patients by
      empowering RTs and engaging families to participate in care. We found that this
      approach was associated with decreased prolonged oxygen use in patients with
      chronic underlying conditions.

PMID- 26195545
TI  - Recurrence of Neonatal Lupus Post-Cord Blood Transplant for Severe Congenital
      Neutropenia.
AB  - Neonatal lupus erythematosus (NLE) is a rare autoimmune disorder associated with
      transplacental migration of maternal autoantibodies against SS-A (Ro) or SS-B
      (La) antigens that results in cardiac, hepatic, cutaneous, and hematologic
      manifestations. Although NLE-associated neutropenia is considered transient and
      benign, neutropenia caused by severe congenital neutropenia (SCN) is life
      threatening. Diagnosing a complicated picture of neonatal neutropenia can be
      challenging because there are many overlapping features between the acquired and
      inherited etiologies. This article highlights this diagnostic challenge with a
      case of delayed diagnosis of SCN due to an initial diagnosis of concurrent NLE.
      Secondary to SCN refractory to granulocyte colony-stimulating factor, our patient
      underwent a matched sibling cord blood transplant. Posttransplant, the patient
      developed recurrence of NLE symptoms, representing the first case of maternally
      transferred autoantibodies causing symptoms in a cord blood recipient. This novel
      finding prompted a review of the standards for collecting, processing, and
      storing of cord blood donations. This article also discusses the importance of
      physician familiarity with the differences and similarities between publicly and
      privately banked cord blood donations to adequately counsel expectant parents. 

PMID- 26195546
TI  - Choriodecidual Group B Streptococcal Infection Induces miR-155-5p in the Fetal
      Lung in Macaca nemestrina.
AB  - The mechanisms underlying fetal lung injury remain poorly defined. MicroRNAs
      (miRNAs) are small noncoding, endogenous RNAs that regulate gene expression and
      have been implicated in the pathogenesis of lung disease. Using a nonhuman
      primate model of choriodecidual infection, we sought to determine if
      differentially expressed miRNAs were associated with acute fetal lung injury.
      After inoculating 10 chronically catheterized pregnant monkeys (Macaca
      nemestrina) with either group B streptococcus (GBS) at 1 * 10(6) CFU (n = 5) or
      saline (n = 5) in the choriodecidual space, we extracted fetal lung mRNA and
      miRNA and profiled the changes in expression by microarray analysis. We
      identified 9 differentially expressed miRNAs in GBS-exposed fetal lungs, but of
      these, only miR-155-5p was validated by quantitative reverse transcription-PCR (P
      = 0.02). Significantly elevated miR-155-5p expression was also observed when
      immortalized human fetal airway epithelial (FeAE) cells were exposed to
      proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha
      [TNF-alpha]). Overexpression of miR-155-5p in FeAE cells in turn increased the
      production of IL-6 and CXCL10/gamma interferon-induced protein 10, which are
      implicated in leukocyte recruitment but also in protection from lung injury.
      Interestingly, while miR-155-5p decreased fibroblast growth factor 9 (FGF9)
      expression in a luciferase reporter assay, FGF9 levels were actually increased in
      GBS-exposed fetal lungs in vivo. FGF9 overexpression is associated with abnormal
      lung development. Thus, upregulation of miR-155-5p may serve as a compensatory
      mechanism to lessen the increase in FGF9 and prevent aberrant lung development.
      Understanding the complicated networks regulating lung development in the setting
      of infection is a key step in identifying how to prevent fetal lung injury
      leading to bronchopulmonary dysplasia. 

PMID- 26195547
TI  - Pseudomonas aeruginosa Quorum Sensing Molecule N-(3-Oxododecanoyl)-L-Homoserine
      Lactone Induces HLA-G Expression in Human Immune Cells.
AB  - HLA-G is a nonclassical class I human leukocyte antigen (HLA) involved in
      mechanisms of immune tolerance. The objective of this study was to determine
      whether N-(3-oxododecanoyl)-l-homoserine lactone (3O-C12-HSL), a quorum sensing
      molecule produced by Pseudomonas aeruginosa, could modify HLA-G expression to
      control the host immune response. We evaluated the ability of 3O-C12-HSL to
      induce HLA-G expression in primary immune cells, monocytes (U937 and THP1), and T
      cell lines (Jurkat) in vitro and analyzed the cellular pathway responsible for
      HLA-G expression. We studied the HLA-G promoter with a luciferase assay and
      interleukin-10 (IL-10) and p38/CREB signaling with enzyme-linked immunosorbent
      assay and immunofluorescence, respectively. We observed that 3O-C12-HSL is able
      to induce HLA-G expression in human monocytes and T cells. We showed that the
      induction of HLA-G by 3O-C12-HSL is p38/CREB and IL-10 dependent. 3O-C12-HSL
      treatment is able to arrest only the U937 cell cycle, possibly due to the
      peculiar expression of the ILT2 receptor in the U937 cell line. Our observations
      suggest HLA-G as a mechanism to create a protected niche for the bacterial
      reservoir, similar to the role of HLA-G molecules during viral infections. 

PMID- 26195548
TI  - Schistosoma mansoni Larvae Do Not Expand or Activate Foxp3+ Regulatory T Cells
      during Their Migratory Phase.
AB  - Foxp3(+) regulatory T (Treg) cells play a key role in suppression of immune
      responses during parasitic helminth infection, both by controlling damaging
      immunopathology and by inhibiting protective immunity. During the patent phase of
      Schistosoma mansoni infection, Foxp3(+) Treg cells are activated and suppress egg
      elicited Th2 responses, but little is known of their induction and role during
      the early prepatent larval stage of infection. We quantified Foxp3(+) Treg cell
      responses during the first 3 weeks of murine S. mansoni infection in C57BL/6
      mice, a time when larval parasites migrate from the skin and transit the lungs en
      route to the hepatic and mesenteric vasculature. In contrast to other helminth
      infections, S. mansoni did not elicit a Foxp3(+) Treg cell response during this
      early phase of infection. We found that the numbers and proportions of Foxp3(+)
      Treg cells remained unchanged in the lungs, draining lymph nodes, and spleens of
      infected mice. There was no increase in the activation status of Foxp3(+) Treg
      cells upon infection as assessed by their expression of CD25, Foxp3, and Helios.
      Furthermore, infection failed to induce Foxp3(+) Treg cells to produce the
      suppressive cytokine interleukin 10 (IL-10). Instead, only CD4(+) Foxp3(-) IL
      4(+) Th2 cells showed increased IL-10 production upon infection. These data
      indicate that Foxp3(+) Treg cells do not play a prominent role in regulating
      immunity to S. mansoni larvae and that the character of the initial immune
      response invoked by S. mansoni parasites contrasts with the responses to other
      parasitic helminth infections that promote rapid Foxp3(+) Treg cell responses. 

PMID- 26195549
TI  - Parasite Manipulation of the Invariant Chain and the Peptide Editor H2-DM Affects
      Major Histocompatibility Complex Class II Antigen Presentation during Toxoplasma
      gondii Infection.
AB  - Toxoplasma gondii is an obligate intracellular protozoan parasite. This
      apicomplexan is the causative agent of toxoplasmosis, a leading cause of central
      nervous system disease in AIDS. It has long been known that T. gondii interferes
      with major histocompatibility complex class II (MHC-II) antigen presentation to
      attenuate CD4(+) T cell responses and establish persisting infections.
      Transcriptional downregulation of MHC-II genes by T. gondii was previously
      established, but the precise mechanisms inhibiting MHC-II function are currently
      unknown. Here, we show that, in addition to transcriptional regulation of MHC-II,
      the parasite modulates the expression of key components of the MHC-II antigen
      presentation pathway, namely, the MHC-II-associated invariant chain (Ii or CD74)
      and the peptide editor H2-DM, in professional antigen-presenting cells (pAPCs).
      Genetic deletion of CD74 restored the ability of infected dendritic cells to
      present a parasite antigen in the context of MHC-II in vitro. CD74 mRNA and
      protein levels were, surprisingly, elevated in infected cells, whereas MHC-II and
      H2-DM expression was inhibited. CD74 accumulated mainly in the endoplasmic
      reticulum (ER), and this phenotype required live parasites, but not active
      replication. Finally, we compared the impacts of genetic deletion of CD74 and H2
      DM genes on parasite dissemination toward lymphoid organs in mice, as well as
      activation of CD4(+) T cells and interferon gamma (IFN-gamma) levels during acute
      infection. Cyst burdens and survival during the chronic phase of infection were
      also evaluated in wild-type and knockout mice. These results highlight the fact
      that the infection is influenced by multiple levels of parasite manipulation of
      the MHC-II antigen presentation pathway. 

PMID- 26195550
TI  - Expression, Purification, and Biological Characterization of Babesia microti
      Apical Membrane Antigen 1.
AB  - The intraerythrocytic apicomplexan Babesia microti, the primary causative agent
      of human babesiosis, is a major public health concern in the United States and
      elsewhere. Apicomplexans utilize a multiprotein complex that includes a type I
      membrane protein called apical membrane antigen 1 (AMA1) to invade host cells. We
      have isolated the full-length B. microti AMA1 (BmAMA1) gene and determined its
      nucleotide sequence, as well as the amino acid sequence of the AMA1 protein. This
      protein contains an N-terminal signal sequence, an extracellular region, a
      transmembrane region, and a short conserved cytoplasmic tail. It shows the same
      domain organization as the AMA1 orthologs from piroplasm, coccidian, and
      haemosporidian apicomplexans but differs from all other currently known
      piroplasmida, including other Babesia and Theileria species, in lacking two
      conserved cysteines in highly variable domain III of the extracellular region.
      Minimal polymorphism was detected in BmAMA1 gene sequences of parasite isolates
      from six babesiosis patients from Nantucket. Immunofluorescence microscopy
      studies showed that BmAMA1 is localized on the cell surface and cytoplasm near
      the apical end of the parasite. Native BmAMA1 from parasite lysate and refolded
      recombinant BmAMA1 (rBmAMA1) expressed in Escherichia coli reacted with a mouse
      anti-BmAMA1 antibody using Western blotting. In vitro binding studies showed that
      both native BmAMA1 and rBmAMA1 bind to human red blood cells (RBCs). This binding
      is trypsin and chymotrypsin treatment sensitive but neuraminidase independent.
      Incubation of B. microti parasites in human RBCs with a mouse anti-BmAMA1
      antibody inhibited parasite growth by 80% in a 24-h assay. Based on its
      antigenically conserved nature and potential role in RBC invasion, BmAMA1 should
      be evaluated as a vaccine candidate. 

PMID- 26195551
TI  - The Poly-gamma-d-Glutamic Acid Capsule Surrogate of the Bacillus anthracis
      Capsule Is a Novel Toll-Like Receptor 2 Agonist.
AB  - Bacillus anthracis is a pathogenic Gram-positive bacterium that causes a highly
      lethal infectious disease, anthrax. The poly-gamma-d-glutamic acid (PGA) capsule
      is one of the major virulence factors of B. anthracis, along with exotoxins. PGA
      enables B. anthracis to escape phagocytosis and immune surveillance. Our previous
      study showed that PGA activates the human macrophage cell line THP-1 and human
      dendritic cells, resulting in the production of the proinflammatory cytokine
      interleukin-1beta (IL-1beta) (M. H. Cho et al., Infect Immun 78:387-392, 2010,
      http://dx.doi.org/10.1128/IAI.00956-09). Here, we investigated PGA-induced
      cytokine responses and related signaling pathways in mouse bone marrow-derived
      macrophages (BMDMs) using Bacillus licheniformis PGA as a surrogate for B.
      anthracis PGA. Upon exposure to PGA, BMDMs produced proinflammatory mediators,
      including tumor necrosis factor alpha (TNF-alpha), IL-6, IL-12p40, and monocyte
      chemoattractant protein 1 (MCP-1), in a concentration-dependent manner. PGA
      stimulated Toll-like receptor 2 (TLR2) but not TLR4 in Chinese hamster ovary
      cells expressing either TLR2 or TLR4. The ability of PGA to induce TNF-alpha and
      IL-6 was retained in TLR4(-/-) but not TLR2(-/-) BMDMs. Blocking experiments with
      specific neutralizing antibodies for TLR1, TLR6, and CD14 showed that TLR6 and
      CD14 also were necessary for PGA-induced inflammatory responses. Furthermore, PGA
      enhanced activation of mitogen-activated protein (MAP) kinases and nuclear factor
      kappa B (NF-kappaB), which are responsible for expression of proinflammatory
      cytokines. Additionally, PGA-induced TNF-alpha production was abrogated not only
      in MyD88(-/-) BMDMs but also in BMDMs pretreated with inhibitors of MAP kinases
      and NF-kappaB. These results suggest that immune responses induced by PGA occur
      via TLR2, TLR6, CD14, and MyD88 through activation of MAP kinase and NF-kappaB
      pathways. 

PMID- 26195552
TI  - Dual Zinc Transporter Systems in Vibrio cholerae Promote Competitive Advantages
      over Gut Microbiome.
AB  - Zinc is an essential trace metal required for numerous cellular processes in all
      forms of life. In order to maintain zinc homeostasis, bacteria have developed
      several transport systems to regulate its uptake. In this study, we investigated
      zinc transport systems in the enteric pathogen Vibrio cholerae, the causative
      agent of cholera. Bioinformatic analysis predicts that two gene clusters, VC2081
      to VC2083 (annotated as zinc utilization genes znuABC) and VC2551 to VC2555
      (annotated as zinc-regulated genes zrgABCDE), are regulated by the putative zinc
      uptake regulator Zur. Using promoter reporter and biochemical assays, we
      confirmed that Zur represses znuABC and zrgABCDE promoters in a Zn(2+)-dependent
      manner. Under Zn(2+)-limiting conditions, we found that mutations in either the
      znuABC or zrgABCDE gene cluster affect bacterial growth, with znuABC mutants
      displaying a more severe growth defect, suggesting that both ZnuABC and ZrgABCDE
      are involved in Zn(2+) uptake and that ZnuABC plays the predominant role.
      Furthermore, we reveal that ZnuABC and ZrgABCDE are important for V. cholerae
      colonization in both infant and adult mouse models, particularly in the presence
      of other intestinal microbiota. Collectively, our studies indicate that these two
      zinc transporter systems play vital roles in maintaining zinc homeostasis during
      V. cholerae growth and pathogenesis. 

PMID- 26195554
TI  - The Legionella pneumophila Siderophore Legiobactin Is a Polycarboxylate That Is
      Identical in Structure to Rhizoferrin.
AB  - Legionella pneumophila, the agent of Legionnaires' disease, secretes a
      siderophore (legiobactin) that promotes bacterial infection of the lung. In past
      work, we determined that cytoplasmic LbtA (from Legiobactin gene A) promotes
      synthesis of legiobactin, inner membrane LbtB aids in export of the siderophore,
      and outer membrane LbtU and inner membrane LbtC help mediate ferrilegiobactin
      uptake and assimilation. However, the past studies examined legiobactin contained
      within bacterial culture supernatants. By utilizing high-pressure liquid
      chromatography that incorporates hydrophilic interaction-based chemistry, we have
      now purified legiobactin from supernatants of virulent strain 130b that is
      suitable for detailed chemical analysis. High-resolution mass spectrometry (MS)
      revealed that the molecular mass of (protonated) legiobactin is 437.140 Da. On
      the basis of the results obtained from both MS analysis and various forms of
      nuclear magnetic resonance, we found that legiobactin is composed of two citric
      acid residues linked by a putrescine bridge and thus is identical in structure to
      rhizoferrin, a polycarboxylate-type siderophore made by many fungi and several
      unrelated bacteria. Both purified legiobactin and rhizoferrin obtained from the
      fungus Cunninghamella elegans were able to promote Fe(3+) uptake by wild-type L.
      pneumophila as well as enhance growth of iron-starved bacteria. These results did
      not occur with 130b mutants lacking lbtU or lbtC, indicating that both
      endogenously made legiobactin and exogenously derived rhizoferrin are assimilated
      by L. pneumophila in an LbtU- and LbtC-dependent manner. 

PMID- 26195553
TI  - The O-Antigen Capsule of Salmonella enterica Serovar Typhimurium Facilitates
      Serum Resistance and Surface Expression of FliC.
AB  - Group IV polysaccharide capsules are common in enteric bacteria and have more
      recently been described in nontyphoidal Salmonella species. Such capsules are
      known as O-antigen (O-Ag) capsules, due to their high degree of similarity to the
      O-Ag of the lipopolysaccharide (LPSO-Ag). Capsular polysaccharides are known
      virulence factors of many bacterial pathogens, facilitating evasion of immune
      recognition and systemic dissemination within the host. Previous studies on the O
      Ag capsule of salmonellae have focused primarily on its role in bacterial surface
      attachment and chronic infection; however, the potential effects of the O-Ag
      capsule on acute pathogenesis have yet to be investigated. While much of the in
      vivo innate immune resistance of Salmonella enterica serovar Typhimurium is
      attributed to the high-molecular-weight LPS, we hypothesized that the O-Ag
      capsule may enhance this resistance by diminishing surface expression of pathogen
      associated molecular patterns, such as flagella, and increasing resistance to
      host immune molecules. To test this hypothesis, O-Ag capsule-deficient mutants
      were constructed, and the loss of O-Ag capsular surface expression was confirmed
      through microscopy and immunoblotting. Loss of O-Ag capsule production did not
      alter bacterial growth or production of LPS. Western blot analysis and confocal
      microscopy revealed that O-Ag capsule-deficient mutants demonstrate reduced
      resistance to killing by human serum. Furthermore, O-Ag capsule-deficient mutants
      produced exclusively phase I flagellin (FliC). Although O-Ag capsule-deficient
      mutants did not exhibit reduced virulence in a murine model of acute infection,
      in vitro results indicate that the O-Ag capsule may function to modify the
      antigenic nature of the bacterial surface, warranting additional investigation of
      a potential role of the structure in pathogenesis. 

PMID- 26195555
TI  - Unexpected Roles for Toll-Like Receptor 4 and TRIF in Intraocular Infection with
      Gram-Positive Bacteria.
AB  - Inflammation caused by infection with Gram-positive bacteria is typically
      initiated by interactions with Toll-like receptor 2 (TLR2). Endophthalmitis, an
      infection and inflammation of the posterior segment of the eye, can lead to
      vision loss when initiated by a virulent microbial pathogen. Endophthalmitis
      caused by Bacillus cereus develops as acute inflammation with infiltrating
      neutrophils, and vision loss is potentially catastrophic. Residual inflammation
      observed during B. cereus endophthalmitis in TLR2(-/-) mice led us to investigate
      additional innate pathways that may trigger intraocular inflammation. We first
      hypothesized that intraocular inflammation during B. cereus endophthalmitis would
      be controlled by MyD88- and TRIF-mediated signaling, since MyD88 and TRIF are the
      major adaptor molecules for all bacterial TLRs. In MyD88(-/-) and TRIF(-/-) mice,
      we observed significantly less intraocular inflammation than in eyes from
      infected C57BL/6J mice, suggesting an important role for these TLR adaptors in B.
      cereus endophthalmitis. These results led to a second hypothesis, that TLR4, the
      only TLR that signals through both MyD88 and TRIF signaling pathways, contributed
      to inflammation during B. cereus endophthalmitis. Surprisingly, B. cereus
      infected TLR4(-/-) eyes also had significantly less intraocular inflammation than
      infected C57BL/6J eyes, indicating an important role for TLR4 in B. cereus
      endophthalmitis. Taken together, our results suggest that TLR4, TRIF, and MyD88
      are important components of the intraocular inflammatory response observed in
      experimental B. cereus endophthalmitis, identifying a novel innate immune
      interaction for B. cereus and for this disease. 

PMID- 26195556
TI  - Candida albicans Quorum Sensing Molecules Stimulate Mouse Macrophage Migration.
AB  - The polymorphic commensal fungus Candida albicans causes life-threatening disease
      via bloodstream and intra-abdominal infections in immunocompromised and
      transplant patients. Although host immune evasion is a common strategy used by
      successful human fungal pathogens, C. albicans provokes recognition by host
      immune cells less capable of destroying it. To accomplish this, C. albicans white
      cells secrete a low-molecular-weight chemoattractive stimulant(s) of macrophages,
      a phagocyte that they are able to survive within and eventually escape from. C.
      albicans opaque cells do not secrete this chemoattractive stimulant(s). We report
      here a physiological mechanism that contributes to the differences in the
      interaction of C. albicans white and opaque cells with macrophages. E,E-Farnesol,
      which is secreted by white cells only, is a potent stimulator of macrophage
      chemokinesis, whose activity is enhanced by yeast cell wall components and
      aromatic alcohols. E,E-farnesol results in up to an 8.5-fold increase in
      macrophage migration in vitro and promotes a 3-fold increase in the peritoneal
      infiltration of macrophages in vivo. Therefore, modulation of farnesol secretion
      to stimulate host immune recognition by macrophages may help explain why this
      commensal is such a successful pathogen. 

PMID- 26195558
TI  - New Insight of Morning Blood Pressure Surge Into the Triggers of Cardiovascular
      Disease-Synergistic Resonance of Blood Pressure Variability.

PMID- 26195557
TI  - Morning Blood Pressure Surge, Dipping, and Risk of Coronary Events in Elderly
      Treated Hypertensive Patients.
AB  - BACKGROUND: The independent prognostic significance of morning surge (MS) of
      blood pressure (BP) is not yet clear. We investigated the association between MS
      of systolic BP and risk of coronary events in elderly treated hypertensive
      patients. METHODS: The occurrence of coronary events was evaluated in 1,191
      elderly treated hypertensive patients (age range 60-90 years). Subjects were
      divided according to tertiles of MS of systolic BP of the population as a whole,
      by dipping status and by group-specific tertiles of MS of systolic BP in dippers
      and nondippers. RESULTS: During the follow-up (9.1 +/- 4.9 years, range 0.4-20
      years), 120 coronary events occurred. In the population as a whole, coronary
      event risk was not significantly associated with tertiles of MS of systolic BP,
      whereas nondippers were at higher risk than dippers. When nondippers and dippers
      were analyzed separately, by group-specific tertiles of MS of systolic BP,
      coronary event risk was associated with MS of systolic BP in dippers but not in
      nondippers. After adjustment for various covariates, Cox regression analysis
      showed that dippers in the third tertile (>23 mm Hg) of MS of systolic BP (hazard
      ratio 1.912, 95% confidence interval 1.048-3.488, P = 0.03) and nondippers
      (hazard ratio 1.739, 95% confidence interval 1.074-2.815, P = 0.02) were at
      higher coronary event risk than dippers with MS of systolic BP <23 mm Hg .
      CONCLUSIONS: In elderly treated hypertensive patients, high MS of systolic BP
      predicts coronary events in dippers but not in nondippers. Nondippers, however,
      show higher risk of coronary events independently of MS in systolic BP.

PMID- 26195559
TI  - Hematological Parameters as Predictors of Cardiovascular Disease in Obstructive
      Sleep Apnea Syndrome Patients.
AB  - We investigated the role of the red cell distribution width (RDW) and other
      parameters including platelet (PLT) count, mean platelet volume (MPV), and
      platelet distribution width (PDW) in patients with obstructive sleep apnea
      syndrome (OSAS) having cardiovascular diseases (CVDs). Patients (n = 142) having
      sleep disorders and who applied for a night polysomnography were included in this
      study. For statistical analysis, chi-square test, bivarite correlation, and
      logistic and stepwise regression tests were used. A positive correlation between
      RDW MPV, RDW, and body mass index as well as PLT and apnea-hypopnea index were
      observed. A negative correlation between AHI and PDW (P= .041) and a positive
      correlation between AHI and PLT (P= .010) were found in the patients >=40 years
      old with CVD. The RDW was higher in patients >=40 years old who had CVD (P=
      .016), and 19% of them had RDW >14%. The PDW (odds ratio = 6.02 [95% confidence
      interval = 1.3-28.2],P= .023) appeared to be associated with increased risk of
      hyperlipidemia in patients with severe OSAS. If these results are confirmed, RDW
      could be used with other markers, especially PLT and PDW, in prediction of CVD in
      patients with severe OSAS. 

PMID- 26195560
TI  - Smoking and Arterial Stiffness.

PMID- 26195561
TI  - Cell Therapy for Critical Limb Ischemia: A Meta-Analysis of Randomized Controlled
      Trials.
AB  - Early-phase trials showed the feasibility and potential efficacy of cell therapy
      in patients with critical limb ischemia (CLI). For systematic review, randomized
      controlled trials (RCTs) of cell therapy versus no cell therapy in CLI were
      searched from PubMed and the Cochrane library databases. Outcome measures
      included major amputation, complete ulcer healing, ankle-brachial index (ABI),
      and all-cause mortality. Data were pooled using 16 RCTs, involving 774 patients.
      Compared with no cell therapy, cell therapy significantly reduced major
      amputation (odds ratio [OR]: 0.54; 95% CI: 0.34-0.87:P= .01) and improved ulcer
      healing (OR: 2.90; 95% confidence interval [CI]: 1.44-5.82;P< .01) and ABI (OR:
      5.91; 95% CI: 1.85-18.86:P< .01). Peripheral blood-derived mononuclear cells (PB
      MNCs; OR: 0.29; 95% CI: 0.12-0.72;P< .01) and bone marrow concentrate (OR: 0.44;
      95% CI: 0.21-0.93;P= .03) significantly lowered the risk of major amputation. The
      PB-MNCs also significantly increased ulcer healing (OR: 5.77; 95% CI: 1.77
      18.87;P< .01). All-cause mortality was similar in both groups (OR: 0.78; 95% CI:
      0.44-1.40;P= .41). However, all estimates were nonsignificant following
      reanalysis using placebo-controlled RCTs only. Cell therapy remains a potential
      therapeutic option in CLI, but further larger placebo-controlled RCTs are needed.

PMID- 26195562
TI  - Trends and sex differences in prescription opioid deaths in British Columbia,
      Canada.
AB  - Increasing rates of prescription opioid-related death are well documented in
      Ontario (ON) but little is known about prescription opioid-related harms in other
      Canadian provinces. Using administrative mortality data from 2004 to 2013, we
      found that rates of prescription opioid-related death in British Columbia (BC)
      were higher but more stable than published rates for ON over the same period.
      Methadone was involved in approximately 25% of the prescription opioid-related
      deaths in BC. The majority of prescription opioid-related deaths among men and
      women were unintentional. Men had higher overall rates of prescription opioid
      related deaths in BC; women had lower rates of prescription opioid-related deaths
      but a larger proportion of them were suicides. Efforts to reduce prescription
      opioid-related deaths must consider sex differences in patterns of prescription
      opioid use and associated harms.

PMID- 26195563
TI  - Pregnancy outcome for fetuses with increased nuchal translucency but normal
      karyotype.
AB  - OBJECTIVE: To investigate pregnancy outcome for fetuses with nuchal translucency
      (NT) >=3.5 mm but normal karyotype in the Stockholm (Sweden) area. METHODS: A
      retrospective population-based cohort study. From 2006 to 2012, fetal NT was
      measured in 55123 singleton pregnancies. There were 341 pregnancies with NT
      thickness >=3.5 mm; 139 had a normal karyotype, 164 had an abnormal karyotype and
      38 were removed from the study. Pregnancy outcome was defined as adverse
      (termination of pregnancy [TOP], miscarriage [MC], intrauterine fetal death
      [IUFD], or delivery of a child with structural defects or genetic disorders), or
      favourable (delivery of a child without any structural defects or genetic
      disorders diagnosed before discharge). RESULTS: Of the 139 high NT pregnancies
      with normal karyotype, 110 (79.2%) resulted in live births, one (0.7%) IUFD, 23
      (16.5%) TOP and five (3.6%) MC. The risk of an adverse pregnancy outcome
      increased with increasing NT. Structural fetal defects were found in 28 (19.5%)
      of pregnancies undergoing second trimester ultrasound screening, of which seven
      resulted in live births and 21 were terminated. The most common structural defect
      was cardiac defects. CONCLUSIONS: Adverse pregnancy outcome increased with
      increasing NT, even with normal karyotype, however, the prognosis is good if the
      second trimester ultrasound screening is normal.

PMID- 26195564
TI  - Gender differences in faecal haemoglobin concentration.

PMID- 26195565
TI  - Assessment of faecal haemoglobin concentration distributions is vital for faecal
      immunochemical test (FIT)-based colorectal cancer screening programmes.

PMID- 26195566
TI  - Atypical Femur Fractures Associated With Diphosphonate Use.
AB  - Osteoporosis-related fractures create a heavy economic and healthcare burden.
      Although diphosphonate medications have been successful at decreasing the risk of
      osteoporotic fragility fractures and have become staples in the treatment of
      osteoporosis, concerns have been raised about the association of diphosphonate
      therapy with spontaneous nonvertebral fractures. Diphosphonate fractures are
      characteristically transverse or slightly oblique in nature and occur in the
      lateral cortex, or tension side, of the subtrochanteric region of the femur where
      diffuse cortical thickening and fracture can be observed on radiographs. A
      multidisciplinary approach incorporating both medical and surgical teams should
      be used in the case of diphosphonate-associated fractures. Future medical and
      surgical developments that augment fracture fixation and counteract diphosphonate
      associated osteoclast apoptosis may play a role in therapy. Although
      diphosphonate use has decreased the rate of osteoporosis-related fractures,
      increased awareness and association with atypical subtrochanteric fractures is an
      important concern for clinicians to keep in mind. 

PMID- 26195567
TI  - Psychological Factors Affecting Rehabilitation and Outcomes Following Elective
      Orthopaedic Surgery.
AB  - Orthopaedic surgery often requires many months of rehabilitation to achieve a
      successful outcome, regardless of subspecialty. Several important psychological
      factors strongly influence pain perceptions, rehabilitation compliance, and
      patient outcomes after common orthopaedic surgeries that require extensive
      rehabilitation, including total joint arthroplasty, anterior cruciate ligament
      reconstruction, and spine surgery for degenerative disease. Early recognition of
      patients exhibiting psychological distress, fear-avoidance behavior, or poor
      perceived self-efficacy or pessimistic personality traits can be used to improve
      preoperative risk stratification for poor rehabilitation or surgical outcomes.
      Several intervention strategies exist to address these psychological factors when
      they appear to contribute suboptimal postoperative rehabilitation or recovery. 

PMID- 26195568
TI  - Genetic Architecture of Natural Variation in Thermal Responses of Arabidopsis.
AB  - Wild strains of Arabidopsis (Arabidopsis thaliana) exhibit extensive natural
      variation in a wide variety of traits, including response to environmental
      changes. Ambient temperature is one of the major external factors that modulates
      plant growth and development. Here, we analyze the genetic architecture of
      natural variation in thermal responses of Arabidopsis. Exploiting wild accessions
      and recombinant inbred lines, we reveal extensive phenotypic variation in
      response to ambient temperature in distinct developmental traits such as
      hypocotyl elongation, root elongation, and flowering time. We show that variation
      in thermal response differs between traits, suggesting that the individual
      phenotypes do not capture all the variation associated with thermal response.
      Genome-wide association studies and quantitative trait locus analyses reveal that
      multiple rare alleles contribute to the genetic architecture of variation in
      thermal response. We identify at least 20 genomic regions that are associated
      with variation in thermal response. Further characterizations of temperature
      sensitivity quantitative trait loci that are shared between traits reveal a role
      for the blue-light receptor CRYPTOCHROME2 (CRY2) in thermosensory growth
      responses. We show the accession Cape Verde Islands is less sensitive to changes
      in ambient temperature, and through transgenic analysis, we demonstrate that
      allelic variation at CRY2 underlies this temperature insensitivity across several
      traits. Transgenic analyses suggest that the allelic effects of CRY2 on thermal
      response are dependent on genetic background suggestive of the presence of
      modifiers. In addition, our results indicate that complex light and temperature
      interactions, in a background-dependent manner, govern growth responses in
      Arabidopsis. 

PMID- 26195570
TI  - Regulation of Orange Carotenoid Protein Activity in Cyanobacterial
      Photoprotection.
AB  - Plants, algae, and cyanobacteria have developed mechanisms to decrease the energy
      arriving at reaction centers to protect themselves from high irradiance. In
      cyanobacteria, the photoactive Orange Carotenoid Protein (OCP) and the
      Fluorescence Recovery Protein are essential elements in this mechanism.
      Absorption of strong blue-green light by the OCP induces carotenoid and protein
      conformational changes converting the orange (inactive) OCP into a red (active)
      OCP. Only the red orange carotenoid protein (OCP(r)) is able to bind to
      phycobilisomes, the cyanobacterial antenna, and to quench excess energy. In this
      work, we have constructed and characterized several OCP mutants and focused on
      the role of the OCP N-terminal arm in photoactivation and excitation energy
      dissipation. The N-terminal arm largely stabilizes the closed orange OCP
      structure by interacting with its C-terminal domain. This avoids photoactivation
      at low irradiance. In addition, it slows the OCP detachment from phycobilisomes
      by hindering fluorescence recovery protein interaction with bound OCP(r). This
      maintains thermal dissipation of excess energy for a longer time. Pro-22, at the
      beginning of the N-terminal arm, has a key role in the correct positioning of the
      arm in OCP(r), enabling strong OCP binding to phycobilisomes, but is not
      essential for photoactivation. Our results also show that the opening of the OCP
      during photoactivation is caused by the movement of the C-terminal domain with
      respect to the N-terminal domain and the N-terminal arm. 

PMID- 26195569
TI  - Elevation of Pollen Mitochondrial DNA Copy Number by WHIRLY2: Altered Respiration
      and Pollen Tube Growth in Arabidopsis.
AB  - In plants, the copy number of the mitochondrial DNA (mtDNA) can be much lower
      than the number of mitochondria. The biological significance and regulatory
      mechanisms of this phenomenon remain poorly understood. Here, using the pollen
      vegetative cell, we examined the role of the Arabidopsis (Arabidopsis thaliana)
      mtDNA-binding protein WHIRLY2 (AtWHY2). AtWHY2 decreases during pollen
      development, in parallel with the rapid degradation of mtDNA; to examine the
      importance of this decrease, we used the pollen vegetative cell-specific promoter
      Lat52 to express AtWHY2. The transgenic plants (LWHY2) had very high mtDNA levels
      in pollen, more than 10 times more than in the wild type (ecotype Columbia-0).
      LWHY2 plants were fertile, morphologically normal, and set seeds; however,
      reciprocal crosses with heterozygous plants showed reduced transmission of LWHY2
      1 through the male and slower growth of LWHY2-1 pollen tubes. We found that LWHY2
      1 pollen had significantly more reactive oxygen species and less ATP compared
      with the wild type, indicating an effect on mitochondrial respiration. These
      findings reveal that AtWHY2 affects mtDNA copy number in pollen and suggest that
      low mtDNA copy numbers might be the normal means by which plant cells maintain
      mitochondrial genetic information. 

PMID- 26195571
TI  - Genome Structure of the Heavy Metal Hyperaccumulator Noccaea caerulescens and Its
      Stability on Metalliferous and Nonmetalliferous Soils.
AB  - Noccaea caerulescens (formerly known as Thlaspi caerulescens), an extremophile
      heavy metal hyperaccumulator model plant in the Brassicaceae family, is a
      morphologically and phenotypically diverse species exhibiting metal tolerance and
      leaf accumulation of zinc, cadmium, and nickel. Here, we provide a detailed
      genome structure of the approximately 267-Mb N. caerulescens genome, which has
      descended from seven chromosomes of the ancestral proto-Calepineae Karyotype (n =
      7) through an unusually high number of pericentric inversions. Genome analysis in
      two other related species, Noccaea jankae and Raparia bulbosa, showed that all
      three species, and thus probably the entire Coluteocarpeae tribe, have descended
      from the proto-Calepineae Karyotype. All three analyzed species share the
      chromosome structure of six out of seven chromosomes and an unusually high metal
      accumulation in leaves, which remains moderate in N. jankae and R. bulbosa and is
      extreme in N. caerulescens. Among these species, N. caerulescens has the most
      derived karyotype, with species-specific inversions on chromosome NC6, which
      grouped onto its bottom arm functionally related genes of zinc and iron metal
      homeostasis comprising the major candidate genes NICOTIANAMINE SYNTHASE2 and ZINC
      INDUCED FACILITATOR-LIKE1. Concurrently, copper and organellar metal homeostasis
      genes, which are functionally unrelated to the extreme traits characteristic of
      N. caerulescens, were grouped onto the top arm of NC6. Compared with Arabidopsis
      thaliana, more distal chromosomal positions in N. caerulescens were enriched
      among more highly expressed metal homeostasis genes but not among other groups of
      genes. Thus, chromosome rearrangements could have facilitated the evolution of
      enhanced metal homeostasis gene expression, a known hallmark of metal
      hyperaccumulation. 

PMID- 26195572
TI  - Epithelial-Myoepithelial Carcinoma of the Salivary Glands: An Analysis of 246
      Cases.
AB  - OBJECTIVE: Epithelial-myoepithelial carcinoma (EMC) is a rare neoplasm of the
      salivary glands. In this study, we aim to examine the demographic,
      clinicopathologic, and survival features of EMC using a population-based
      approach. STUDY DESIGN AND SETTING: Retrospective cohort study. SUBJECTS AND
      METHODS: The Surveillance, Epidemiology, and End Result (SEER) database (1973
      2010) was queried for EMC of the major salivary glands. Data were analyzed with
      respect to various demographic and clinicopathologic factors. Survival was
      analyzed using the Kaplan-Meier and Cox proportional hazards models. RESULTS: In
      total, 246 cases were available for frequency analysis and 207 for survival
      analysis. Mean +/- SD age at diagnosis was 63.8 +/- 15.4 years. EMC affected
      females more frequently (57.3%). Distant metastases were present at diagnosis in
      only 4.5% of cases. Overall disease-specific survival (DSS) at 60, 120, and 180
      months was 91.3%, 90.2%, and 80.7%, respectively. Patients with low-grade
      histology had significantly better survival at 180 months relative to those with
      high-grade tumors (90.6% vs 0.0%, P = .0246). When stratified by tumor size,
      patients with lesions >4 cm had the worst survival at 180 months (58.8%, P =
      .0003). All but 9 of the 207 cases available for survival analysis underwent
      surgery. A total of 85 patients (41.1%) received radiotherapy in addition to
      surgery. No survival benefit was noted for patients who received radiotherapy
      compared with those who did not (P = .4832). CONCLUSION: This report represents
      the largest series of EMC to date. Despite being regarded as a low-grade,
      indolent tumor, a significant fraction of our cohort underwent radiotherapy in
      addition to surgery, with no apparent added survival benefit.

PMID- 26195573
TI  - The Validity of Self-reported Recent Smoking in Head and Neck Cancer Surgical
      Patients.
AB  - OBJECTIVE: In cancer patients, cigarette smoking causes poorer response to
      treatment, treatment toxicity, increased risk of recurrence, higher surgical
      complication rates, and poorer overall survival. As such a significant
      determinant of patient prognosis, accurate classification of current smoking
      status is important. Self-reported smoking status may lead to misclassification
      if patients conceal their true status. The purpose of this study was to assess
      the validity of self-reported tobacco use during the previous 48 hours in head
      and neck cancer patients on the day of surgery. STUDY DESIGN: Cross-sectional.
      SETTING: Two academic medical centers in the southeastern United States. SUBJECTS
      AND METHODS: On the day of surgery, 108 head and neck cancer patients completed a
      survey asking about tobacco use during the past 48 hours and had semi
      quantitative levels of urinary cotinine measured to biochemically validate self
      reported recent smoking. RESULTS: Self-reported smoking yielded a sensitivity of
      60.9% (95% CI, 45.4%-74.9%) and a specificity of 98.4% (95% CI, 91.3%-100.0%).
      The sensitivity increased to 76.1% (95% CI, 61.2%-87.4%) when allowing for the
      possibility that exposure to secondhand smoke or use of nicotine-containing
      products could have caused a positive cotinine test. CONCLUSION: In this patient
      population, self-reported recent smoking yielded a high (39%) proportion of false
      negatives, and even 24% remained false-negatives after allowing for other sources
      of nicotine exposure. This magnitude of underreporting combined with the
      importance of tobacco use to patient prognosis supports the need for routinely
      biochemically verifying recent tobacco use in self-reported nonsmokers within the
      clinical setting.

PMID- 26195574
TI  - The Lymphatic Malformation Function (LMF) Instrument.
AB  - OBJECTIVE: The Lymphatic Malformation Function (LMF) instrument is a preliminary
      parent-report assessment designed to measure outcomes in children with
      cervicofacial lymphatic malformation (LM). This study aimed to assess the
      measurement properties of the LMF, refine it, test criterion validity, and
      evaluate the test-retest reliability. STUDY DESIGN: Cross-sectional. SETTING: Two
      pediatric tertiary referral centers. SUBJECTS: Parents of 60 children from 6
      months to 15 years old with cervicofacial LM. METHODS: Parents were recruited via
      mail and online. The LMF was administered on paper or online initially and again
      within 21 days. Response distributions and interitem correlations were examined
      for item reduction. Exploratory factor analysis was conducted on retained items.
      Cronbach's alpha, Spearman correlation, and intraclass correlation (ICC)
      coefficients were calculated to test internal consistency, criterion validity
      (compared to stage), and test-retest reliability, respectively. RESULTS: One item
      was removed due to a floor effect. The response scale was collapsed from a 5
      point scale to a 3-point scale due to skewness. Six items were discarded due to
      redundancy (interitem correlations >0.7); 2 items were discarded due to factor
      loadings <0.4. Exploratory factor analysis revealed a 2-factor structure
      explaining 84% of variance, and the domains Signs and Impacts had good internal
      consistency (all Cronbach's alpha >0.80 and <0.90), significant association with
      stage (P < .05), and good overall test-retest reliability (ICC, 0.82).
      CONCLUSION: The LMF has been refined into a 12-item, 2-domain instrument
      measuring LM-specific signs and impacts with internal consistency, criterion
      validity, and test-retest reliability.

PMID- 26195575
TI  - Optimal Management of a 2-Hour-Old Newborn With Severe Congenital Subglottic
      Stenosis and Multiple Congenital Heart Diseases.
AB  - INTRODUCTION: Congenital subglottic stenosis (C-SGS) is the third most common
      congenital anomaly of the larynx. It necessitates tracheotomy in newborns if it
      causes severe airway obstruction. When the negative impact of tracheostomy cannot
      be tolerated, as in presence of congenital heart disease requiring further
      surgical intervention, other alternative procedures are required. This case
      report is the first of its kind reporting airway expansion in a neonate in the
      first few hours after birth. CASE REPORT: A 38-week-fetus male was born with
      multiple congenital heart anomalies and C-SGS of grade III. Single-stage
      laryngotracheoplasty (SS-LTP) with anterior thyroid alar cartilage (TAC) grafting
      was performed. Our team was fully aware of all potential risks during SS-LTP
      procedure in such debilitated patient. DISCUSSION: Treatment of C-SGS in
      premature neonates is tracheostomy to avoid prolonged intubation. In some cases,
      tracheostomy is not a good option as in presence of congenital heart disease
      necessitating urgent further surgical interventions. Among all surgical
      procedures to augment the airway without tracheostomy, SS-LTP with placement of
      anterior TAC graft was our choice. CONCLUSION: This case report demonstrated that
      SS-LTP with anterior TAC graft can be performed in a newborn with severe C-SGS
      and congenital heart disease. It can alleviate the need for tracheostomy and
      avoid unnecessary delay for subsequent cardiac interventions. However, further
      study is likely needed to make a definitive statement of its safety and efficacy.

PMID- 26195576
TI  - Augmentation Autologous Adipose Injections in the Larynx.
AB  - OBJECTIVE: Autologous adipose injection (AAI) is a recognized method for vocal
      fold augmentation. The study's purpose is to explore short- and long-term
      outcomes of AAI. METHODS: Retrospective chart review of 43 patients undergoing
      AAI was performed; patient perception of outcome, Voice Handicap Index (VHI),
      maximum phonatory time (MPT), and disposition were evaluated. RESULTS: Over 5
      years, 43 AAI patients had documented postoperative follow-up (25 paralysis, 8
      paresis, 9 bowing/presbylarynges, and 5 scar/sulci). Mean follow-up was 32 weeks.
      There was gradual patient loss to follow-up. Thirty-nine of 40 (98%) had patient
      reported improvement at 6 weeks, 28 of 34 (82%) had improvement at 2 to 6 months,
      with 10 of 12 (83%) sustaining their improvement for >1 year. Significant
      improvement in mean VHI was observed at 4 to 6 weeks (mean reduction, 26; P <
      .0001) and 2 to 6 months (mean reduction, 23; P < .0001). Improvement in mean MPT
      was observed at 4 to 6 weeks (mean increase, 8 s; P < .0001), 2 to 6 months (6 s;
      P = .007), and >1 year (4 s; P = .03). Eight patients went on to medialization
      laryngoplasty. CONCLUSION: AAI successfully augments vocal folds in short-term
      outcomes with some gradual decrease in effectiveness. Although patient attrition
      limited conclusions, objective long-term benefit may occur in >50% of patients.

PMID- 26195577
TI  - Histopathology of the Inner Ear in a Case With Recent Onset of Cogan's Syndrome:
      Evidence for Vasculitis.
AB  - The association of sensorineural hearing loss and vertigo with inflammatory eye
      disease, usually interstitial keratitis, has been called Cogan's syndrome. The
      pathogenesis of Cogan's syndrome is unknown, but it has been assumed to be an
      immune mediated disorder with vasculitis. The histopathology of the inner ear in
      Cogan's syndrome has been described in 6 case reports. Although common pathologic
      findings in these reports include degeneration of the auditory and vestibular
      neuroepithelium, endolymphatic hydrops, fibrosis, and new bone formation, direct
      pathologic evidence of a vasculitis has not been published. A possible reason for
      this failure to identify vasculitis was a substantial delay (range, 4-40 years)
      between the onset of symptoms and examination of the otopathology. In the current
      case report, the patient had both auditory and vestibular symptoms and
      interstitial keratitis with a time delay of only 2 to 4 weeks between symptoms
      and death. Evidence of a vasculitis as a possible underlying etiology included
      H&E histopathology and anti-CD45 immunostaining of vessels both in the auditory
      and vestibular systems, supporting the hypothesis of a vasculitis as a mechanism
      in this disorder. 

PMID- 26195579
TI  - Lingual Raynaud phenomenon.

PMID- 26195578
TI  - A comparison of the stages at which cancer is diagnosed in physicians and in the
      general population in Taiwan.
AB  - BACKGROUND: Previous investigations have reported that physicians tend to neglect
      their own health care; however, they may also use their professional knowledge
      and networks to engage in healthier lifestyles or seek prompt health services. We
      sought to determine whether the stage at which cancer is diagnosed differs
      between physicians and nonphysicians. METHODS: We conducted a nationwide matched
      cohort study over a period of 14 years in Taiwan. We accessed data from two
      national databases: the National Health Insurance Research Database and the
      Taiwan Cancer Registry File. We collected data on all patients with the 6 most
      common cancers in Taiwan (hepatoma, lung, colorectal, oral, female breast and
      cervical cancer) from 1999 to 2012. We excluded patients less than 25 years of
      age, as well as those with a history of organ transplantation, cancer or AIDS. We
      used propensity score matching for age, sex, residence and income to select
      members for the control (nonphysicians) and experimental (physicians) groups at a
      5:1 ratio. We used chi(2) tests to analyze the distribution of incident cancer
      stages among physicians and nonphysicians. We compared these associations using
      multinomial logistic regression. We performed sensitivity analyses for subgroups
      of doctors and cancers. RESULTS: We identified 274,003 patients with cancer, 542
      of whom were physicians. After propensity score matching, we assigned 536
      physicians to the experimental group and 2680 nonphysicians to the control group.
      We found no significant differences in cancer stage distributions between
      physicians and controls. Multinomial logistic regression and sensitivity analyses
      showed similar cancer stages in most scenarios; however, physicians had 2.64-fold
      higher risk of having stage IV cancer at diagnosis in cases of female breast and
      cervical cancer. INTERPRETATION: In this cohort of physicians in Taiwan, cancer
      was not diagnosed at earlier stages than in nonphysicians, with the exception of
      stage IV cancer of the cervix and female breast.

PMID- 26195580
TI  - Dispensaries: the Wild West of Vancouver.

PMID- 26195581
TI  - Competing interests are a complex problem.

PMID- 26195582
TI  - Nova Scotia targets orthopedic wait times.

PMID- 26195583
TI  - Au-dela des yeux glaces.

PMID- 26195584
TI  - Adopting global guidelines for air pollution: protecting the health of Canadians.

PMID- 26195585
TI  - Cardiac platypnea-orthodeoxia syndrome in a 73-year-old woman.

PMID- 26195586
TI  - Ebola needed better coordinated Canadian response.

PMID- 26195587
TI  - Bidirectional triggering association between migraine and restless legs syndrome:
      A diary study.
AB  - OBJECTIVE: Migraine is comorbid with restless legs syndrome (RLS). However, the
      temporal association between these two episodic disorders remains elusive. The
      current study investigated the temporal relationship between migraine and RLS
      attacks. METHODS: Migraine patients with RLS were recruited from a headache
      clinic. Patients with symptomatic RLS, RLS mimics, daily headaches, or daily RLS
      attacks were excluded. The patients recorded their headaches and RLS attacks for
      two weeks in a diary. The severity of each headache or RLS attack was rated on a
      four-point (0-3) Likert scale. Logit-normal, random-effects models were employed
      to estimate the odds ratios (ORs) for the temporal association between migraine
      and RLS attacks. RESULTS: Thirty migraine patients with RLS (28 F/2 M, mean age
      35.5 +/- 9.0 years) completed the study. On the basis of 420 daily diary records,
      migraine attacks were associated with subsequent RLS attacks occurring on the
      same and next nights (OR = 6.94, 95% confidence interval (CI) = 4.39-11.0 and OR
      = 3.00, CI = 1.92-4.68; both ITALIC! p < 0.001). RLS attacks were associated with
      subsequent migraine attacks only on Day 1 (OR = 1.97 (CI = 1.3-2.98; ITALIC! p =
      0.01). Overall, the frequencies of migraine and RLS attacks in two weeks were
      correlated (Spearman's correlation = 0.56, ITALIC! p = 0.001). CONCLUSIONS: Our
      study results showed a bidirectional triggering association between migraine and
      RLS attacks. The association was stronger and lasted longer for migraine
      triggering subsequent RLS than that for vice versa.

PMID- 26195588
TI  - Evaluating the Impact of Information Technology Tools to Support the Asthma
      Medical Home.
AB  - This study aimed to evaluate the impact of information technology tools on the
      outcomes of children with asthma in the medical home. A registry was established
      for children aged 4 to 18 years with an ICD-9 code for asthma. Changes to the
      electronic health record included modifications to notes, care plans, and orders.
      A retrospective analysis of emergency department and in-patient utilization for a
      cohort of patients was conducted from July 2009 through June 2013. Of the study
      population (n = 1217), 65% had a classification of asthma severity and 63% were
      risk-stratified. Seventy percent had a control assessment at least once. Care
      plan use increased from 5% to 22% and enrollment in care coordination increased
      from 0.1% to 4%. After 3 years, there was a reduction of emergency department and
      inpatient admissions for asthma (P < .05 and P < .005, respectively). The
      implementation of information technology tools was associated with improved
      asthma outcomes. 

PMID- 26195589
TI  - Vinculin is required for cell polarization, migration, and extracellular matrix
      remodeling in 3D collagen.
AB  - Vinculin is filamentous (F)-actin-binding protein enriched in integrin-based
      adhesions to the extracellular matrix (ECM). Whereas studies in 2-dimensional
      (2D) tissue culture models have suggested that vinculin negatively regulates cell
      migration by promoting cytoskeleton-ECM coupling to strengthen and stabilize
      adhesions, its role in regulating cell migration in more physiologic, 3
      dimensional (3D) environments is unclear. To address the role of vinculin in 3D
      cell migration, we analyzed the morphodynamics, migration, and ECM remodeling of
      primary murine embryonic fibroblasts (MEFs) with cre/loxP-mediated vinculin gene
      disruption in 3D collagen I cultures. We found that vinculin promoted 3D cell
      migration by increasing directional persistence. Vinculin was necessary for
      persistent cell protrusion, cell elongation, and stable cell orientation in 3D
      collagen, but was dispensable for lamellipodia formation, suggesting that
      vinculin-mediated cell adhesion to the ECM is needed to convert actin-based cell
      protrusion into persistent cell shape change and migration. Consistent with this
      finding, vinculin was necessary for efficient traction force generation in 3D
      collagen without affecting myosin II activity and promoted 3D collagen fiber
      alignment and macroscopical gel contraction. Our results suggest that vinculin
      promotes directionally persistent cell migration and tension-dependent ECM
      remodeling in complex 3D environments by increasing cell-ECM adhesion and
      traction force generation.

PMID- 26195590
TI  - Novel cell-penetrating peptide targeting mitochondria.
AB  - Cell-penetrating peptides (CPPs) are short, nontoxic peptides with cationic
      and/or amphipathic properties able to cross the cellular membrane. CPPs are used
      for the delivery of a wide variety of cargoes, such as proteins,
      oligonucleotides, and therapeutic molecules. The aim of the present study was to
      synthesize unusually small novel CPPs targeting mitochondria based on the Szeto
      Schiller peptide (SS-31) to influence intramitochondrial processes and to improve
      the biologic effects. All the peptides used were synthesized manually using 9
      fluorenylmethyloxycarbonyl chemistry. In the first part of the study, HeLa 705,
      U87, and bEnd.3 cells were used as in vitro delivery model. Cells were incubated
      for 24 h at 37 degrees C and 5% CO2 with different concentrations of our
      peptides. Cell proliferation assay was performed to evaluate cell viability.
      Biologic effects such as mitochondrial membrane potential and antioxidant
      activity were evaluated. H2O2 was used as positive control. Uptake studies were
      performed using peptides conjugated with 5(6)-carboxyfluorescein (FAM).
      Fluorescent microscopy was used to determine presence and localization of
      peptides into the cells. Isolated mitochondria from pretreated cells and
      mitochondria treated after isolation were used to confirm the targeting ability
      of the peptide. Uptake of FAM alone was used as negative control. Microscopy
      studies confirmed the ability of peptides to penetrate cell. Localization
      analysis showed increase in uptake by 35% compared with SS-31. Mitochondrial CPP
      1 (mtCPP-1) had no effect on mitochondrial membrane potential and prevented
      reactive oxygen species formation in bEnd.3 cells by 2-fold compared with SS-31.
      No cytotoxicity was observed even at high concentration (100 uM). These data
      suggest that mtCPP-1 is a mitochondrial CPP and protect mitochondria from
      oxidative damage due to its own antioxidant activities.

PMID- 26195591
TI  - Cyclic Di-GMP Signaling Contributes to Pseudomonas aeruginosa-Mediated Catheter
      Associated Urinary Tract Infection.
AB  - Bis-(3'-5') cyclic dimeric GMP (c-di-GMP) controls the lifestyle transition
      between the sessile and motile states in many Gram-negative bacteria, including
      the opportunistic human pathogen Pseudomonas aeruginosa. Under laboratory
      conditions, high concentrations of c-di-GMP decrease motility and promote biofilm
      formation, while low concentrations of c-di-GMP promote motility and decease
      biofilm formation. Here we sought to determine the contribution of c-di-GMP
      signaling to biofilm formation during P. aeruginosa-mediated catheter-associated
      urinary tract infection (CAUTI). Using a murine CAUTI model, a decrease in CFU
      was detected in the bladders and kidneys of mice infected with strains
      overexpressing the phosphodiesterases (PDEs) encoded by PA3947 and PA2133
      compared to those infected with wild-type P. aeruginosa. Conversely,
      overexpression of the diguanylate cyclases (DGCs) encoded by PA3702 and PA1107
      increased the number of bacteria in bladder and significantly increased
      dissemination of bacteria to the kidneys compared to wild-type infection. To
      determine which of the DGCs and PDEs contribute to c-di-GMP signaling during
      infection, a panel of PA14 in-frame deletion mutants lacking DGCs and PDEs were
      tested in the CAUTI model. Results from these infections revealed five mutants,
      three containing GGDEF domains (DeltaPA14_26970, DeltaPA14_72420, and DeltasiaD)
      and two containing dual GGDEF-EAL domains (DeltamorA and DeltaPA14_07500), with
      decreased colonization of the bladder and dissemination to the kidneys. These
      results indicate that c-di-GMP signaling influences P. aeruginosa-mediated
      biofilms during CAUTI. IMPORTANCE: Biofilm-based infections are an important
      cause of nosocomial infections, since they resist the immune response and
      traditional antibiotic treatment. Cyclic di-GMP (c-di-GMP) is a second messenger
      that promotes biofilm formation in many Gram-negative pathogens, including
      Pseudomonas aeruginosa. Here we determined the contribution of c-di-GMP signaling
      to catheter-associated urinary tract infection (CAUTI), an animal model of
      biofilm-based infection. P. aeruginosa with elevated levels of c-di-GMP during
      the initial infection produces an increased bacterial burden in the bladder and
      kidneys. Conversely, low concentrations of c-di-GMP decreased the bacterial
      burden in the bladder and kidneys. We screened a library of mutants with
      mutations in genes regulating c-di-GMP signaling and found several mutants that
      altered colonization of the urinary tract. This study implicates c-di-GMP
      signaling during CAUTI.

PMID- 26195592
TI  - Lessons in Fundamental Mechanisms and Diverse Adaptations from the 2015 Bacterial
      Locomotion and Signal Transduction Meeting.
AB  - In response to rapid changes in their environment, bacteria control a number of
      processes, including motility, cell division, biofilm formation, and virulence.
      Research presented in January 2015 at the biennial Bacterial Locomotion and
      Signal Transduction (BLAST) meeting in Tucson, AZ, illustrates the elegant
      complexity of the nanoarrays, nanomachines, and networks of interacting proteins
      that mediate such processes. Studies employing an array of biophysical, genetic,
      cell biology, and mathematical methods are providing an increasingly detailed
      understanding of the mechanisms of these systems within well-studied bacteria.
      Furthermore, comparisons of these processes in diverse bacterial species are
      providing insight into novel regulatory and functional mechanisms. This review
      summarizes research presented at the BLAST meeting on these fundamental
      mechanisms and diverse adaptations, including findings of importance for
      applications involving bacteria of medical or agricultural relevance. 

PMID- 26195593
TI  - RecF and RecR Play Critical Roles in the Homologous Recombination and Single
      Strand Annealing Pathways of Mycobacteria.
AB  - Mycobacteria encode three DNA double-strand break repair pathways: (i) RecA
      dependent homologous recombination (HR), (ii) Ku-dependent nonhomologous end
      joining (NHEJ), and (iii) RecBCD-dependent single-strand annealing (SSA).
      Mycobacterial HR has two presynaptic pathway options that rely on the helicase
      nuclease AdnAB and the strand annealing protein RecO, respectively. Ablation of
      adnAB or recO individually causes partial impairment of HR, but loss of adnAB and
      recO in combination abolishes HR. RecO, which can accelerate annealing of single
      stranded DNA in vitro, also participates in the SSA pathway. The functions of
      RecF and RecR, which, in other model bacteria, function in concert with RecO as
      mediators of RecA loading, have not been examined in mycobacteria. Here, we
      present a genetic analysis of recF and recR in mycobacterial recombination. We
      find that RecF, like RecO, participates in the AdnAB-independent arm of the HR
      pathway and in SSA. In contrast, RecR is required for all HR in mycobacteria and
      for SSA. The essentiality of RecR as an agent of HR is yet another distinctive
      feature of mycobacterial DNA repair.IMPORTANCE This study clarifies the molecular
      requirements for homologous recombination in mycobacteria. Specifically, we
      demonstrate that RecF and RecR play important roles in both the RecA-dependent
      homologous recombination and RecA-independent single-strand annealing pathways.
      Coupled with our previous findings (R. Gupta, M. Ryzhikov, O. Koroleva, M.
      Unciuleac, S. Shuman, S. Korolev, and M. S. Glickman, Nucleic Acids Res 41:2284
      2295, 2013, http://dx.doi.org/10.1093/nar/gks1298), these results revise our view
      of mycobacterial recombination and place the RecFOR system in a central position
      in homology-dependent DNA repair. 

PMID- 26195594
TI  - Regulation Mechanism of the ald Gene Encoding Alanine Dehydrogenase in
      Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC Family
      Regulator AldR.
AB  - In the presence of alanine, AldR, which belongs to the Lrp/AsnC family of
      transcriptional regulators and regulates ald encoding alanine dehydrogenase in
      Mycobacterium smegmatis, changes its quaternary structure from a homodimer to an
      octamer with an open-ring conformation. Four AldR-binding sites (O2, O1, O4, and
      O3) with a consensus sequence of GA/T-N2-NWW/WWN-N2-A/TC were identified upstream
      of the M. smegmatis ald gene by means of DNase I footprinting analysis. O2, O1,
      and O4 are required for the induction of ald expression by alanine, while O3 is
      directly involved in the repression of ald expression. In addition to O3, both O1
      and O4 are also necessary for full repression of ald expression in the absence of
      alanine, due to cooperative binding of AldR dimers to O1, O4, and O3. Binding of
      a molecule of the AldR octamer to the ald control region was demonstrated to
      require two AldR-binding sites separated by three helical turns between their
      centers and one additional binding site that is in phase with the two AldR
      binding sites. The cooperative binding of AldR dimers to DNA requires three AldR
      binding sites that are aligned with a periodicity of three helical turns. The
      aldR gene is negatively autoregulated independently of alanine. Comparative
      analysis of ald expression of M. smegmatis and Mycobacterium tuberculosis in
      conjunction with sequence analysis of both ald control regions led us to suggest
      that the expression of the ald genes in both mycobacterial species is regulated
      by the same mechanism. IMPORTANCE: In mycobacteria, alanine dehydrogenase (Ald)
      is the enzyme required both to utilize alanine as a nitrogen source and to grow
      under hypoxic conditions by maintaining the redox state of the NADH/NAD(+) pool.
      Expression of the ald gene was reported to be regulated by the AldR regulator
      that belongs to the Lrp/AsnC (feast/famine) family, but the underlying mechanism
      was unknown. This study revealed the regulation mechanism of ald in Mycobacterium
      smegmatis and Mycobacterium tuberculosis. Furthermore, a generalized arrangement
      pattern of cis-acting regulatory sites for Lrp/AsnC (feast/famine) family
      regulators is suggested in this study.

PMID- 26195595
TI  - Function of the Histone-Like Protein H-NS in Motility of Escherichia coli:
      Multiple Regulatory Roles Rather than Direct Action at the Flagellar Motor.
AB  - A number of investigations of Escherichia coli have suggested that the DNA
      binding protein H-NS, in addition to its well-known functions in chromosome
      organization and gene regulation, interacts directly with the flagellar motor to
      modulate its function. Here, in a study initially aimed at characterizing the H
      NS/motor interaction further, we identify problems and limitations in the
      previous work that substantially weaken the case for a direct H-NS/motor
      interaction. Null hns mutants are immotile, largely owing to the downregulation
      of the flagellar master regulators FlhD and FlhC. We, and others, previously
      reported that an hns mutant remains poorly motile even when FlhDC are expressed
      constitutively. In the present work, we use better-engineered strains to show
      that the motility defect in a Deltahns, FlhDC-constitutive strain is milder than
      that reported previously and does not point to a direct action of H-NS at the
      motor. H-NS regulates numerous genes and might influence motility via a number of
      regulatory molecules besides FlhDC. To examine the sources of the motility defect
      that persists in an FlhDC-constitutive Deltahns mutant, we measured transcript
      levels and overexpression effects of a number of genes in candidate regulatory
      pathways. The results indicate that H-NS influences motility via multiple
      regulatory linkages that include, minimally, the messenger molecule cyclic di
      GMP, the biofilm regulatory protein CsgD, and the sigma factors sigma(S) and
      sigma(F). The results are in accordance with the more standard view of H-NS as a
      regulator of gene expression rather than a direct modulator of flagellar motor
      performance. IMPORTANCE: Data from a number of previous studies have been taken
      to indicate that the nucleoid-organizing protein H-NS influences motility not
      only by its well-known DNA-based mechanisms but also by binding directly to the
      flagellar motor to alter function. In this study, H-NS is shown to influence
      motility through diverse regulatory pathways, but a direct interaction with the
      motor is not supported. Previous indications of a direct action at the motor
      appear to be related to the use of nonnull strains and, in some cases, a failure
      to effectively bypass the requirement for H-NS in the expression of the flagellar
      regulon. These findings call for a substantially revised interpretation of the
      literature concerning H-NS and flagellar motility and highlight the importance of
      H-NS in diverse regulatory processes involved in the motile-sessile transition.

PMID- 26195596
TI  - Quorum Sensing Protects Pseudomonas aeruginosa against Cheating by Other Species
      in a Laboratory Coculture Model.
AB  - Many species of bacteria use a cell-cell communication system called quorum
      sensing (QS) to coordinate group activities. QS systems frequently regulate the
      production of exoproducts. Some of these products, such as proteases, are "public
      goods" that are shared among the population and vulnerable to cheating by
      nonproducing members of the population. Because the QS system of the
      opportunistic pathogen Pseudomonas aeruginosa regulates several public goods, it
      can serve as a model for studying cooperation. Bacteria also commonly regulate
      antimicrobial production through QS. In this study, we focused on the hypothesis
      that QS-regulated antimicrobials may be important for P. aeruginosa to protect
      against cheating by another bacterial species, Burkholderia multivorans. We
      assessed laboratory cocultures of P. aeruginosa and B. multivorans and
      investigated the importance of three P. aeruginosa QS-regulated antimicrobials,
      hydrogen cyanide, rhamnolipids, and phenazines, for competition. We found that P.
      aeruginosa dominates cocultures with B. multivorans and that the three
      antimicrobials together promote P. aeruginosa competitiveness, with hydrogen
      cyanide contributing the greatest effect. We show that these QS-regulated
      antimicrobials are also critical for P. aeruginosa to prevent B. multivorans from
      cheating under nutrient conditions where both species require a P. aeruginosa
      quorum-regulated protease for growth. Together our results highlight the
      importance of antimicrobials in protecting cooperating populations from
      exploitation by other species that can act as cheaters. IMPORTANCE: Cooperative
      behaviors are threatened by social cheating, wherein individuals do not produce
      but nonetheless benefit from shared public goods. Bacteria have been shown to use
      several genetic mechanisms to restrain the emergence of cheaters from within the
      population, but public goods might also be used by other bacterial species in the
      vicinity. We demonstrate that a public good produced by Pseudomonas aeruginosa
      can be used by another species, Burkholderia multivorans, to obtain carbon and
      energy. We also show that P. aeruginosa antimicrobials that are coregulated with
      the public good prevent invasion by the cheating species. Our results demonstrate
      that cross-species cheating can occur and that coregulation of public goods with
      antimicrobials may stabilize cooperative behavior in mixed microbial communities.

PMID- 26195597
TI  - Enzymatic Synthesis and Functional Characterization of Bioactive Microcin C-Like
      Compounds with Altered Peptide Sequence and Length.
AB  - Escherichia coli microcin C (McC) consists of a ribosomally synthesized
      heptapeptide attached to a modified adenosine. McC is actively taken up by
      sensitive Escherichia coli strains through the YejABEF transporter. Inside the
      cell, McC is processed by aminopeptidases, which release nonhydrolyzable
      aminoacyl adenylate, an inhibitor of aspartyl-tRNA synthetase. McC is synthesized
      by the MccB enzyme, which terminally adenylates the MccA heptapeptide precursor
      MRTGNAN. Earlier, McC analogs with shortened peptide lengths were prepared by
      total chemical synthesis and were shown to have strongly reduced biological
      activity due to decreased uptake. Variants with longer peptides were difficult to
      synthesize, however. Here, we used recombinant MccB to prepare and characterize
      McC-like molecules with altered peptide moieties, including extended peptide
      lengths. We find that N-terminal extensions of E. coli MccA heptapeptide do not
      affect MccB-catalyzed adenylation and that some extended-peptide-length McC
      analogs show improved biological activity. When the peptide length reaches 20
      amino acids, both YejABEF and SbmA can perform facilitated transport of toxic
      peptide adenylates inside the cell. A C-terminal fusion of the carrier maltose
      binding protein (MBP) with the MccA peptide is also recognized by MccB in vivo
      and in vitro, allowing highly specific adenylation and/or radioactive labeling of
      cellular proteins. IMPORTANCE: Enzymatic adenylation of chemically synthesized
      peptides allowed us to generate biologically active derivatives of the peptide
      nucleotide antibiotic microcin C with improved bioactivity and altered entry
      routes into target cells, opening the way for development of various McC-based
      antibacterial compounds not found in nature.

PMID- 26195598
TI  - Transposon Mutagenesis Paired with Deep Sequencing of Caulobacter crescentus
      under Uranium Stress Reveals Genes Essential for Detoxification and Stress
      Tolerance.
AB  - The ubiquitous aquatic bacterium Caulobacter crescentus is highly resistant to
      uranium (U) and facilitates U biomineralization and thus holds promise as an
      agent of U bioremediation. To gain an understanding of how C. crescentus
      tolerates U, we employed transposon (Tn) mutagenesis paired with deep sequencing
      (Tn-seq) in a global screen for genomic elements required for U resistance. Of
      the 3,879 annotated genes in the C. crescentus genome, 37 were found to be
      specifically associated with fitness under U stress, 15 of which were
      subsequently tested through mutational analysis. Systematic deletion analysis
      revealed that mutants lacking outer membrane transporters (rsaFa and rsaFb), a
      stress-responsive transcription factor (cztR), or a ppGpp synthetase/hydrolase
      (spoT) exhibited a significantly lower survival rate under U stress. RsaFa and
      RsaFb, which are homologues of TolC in Escherichia coli, have previously been
      shown to mediate S-layer export. Transcriptional analysis revealed upregulation
      of rsaFa and rsaFb by 4- and 10-fold, respectively, in the presence of U. We
      additionally show that rsaFa mutants accumulated higher levels of U than the wild
      type, with no significant increase in oxidative stress levels. Our results
      suggest a function for RsaFa and RsaFb in U efflux and/or maintenance of membrane
      integrity during U stress. In addition, we present data implicating CztR and SpoT
      in resistance to U stress. Together, our findings reveal novel gene targets that
      are key to understanding the molecular mechanisms of U resistance in C.
      crescentus. IMPORTANCE: Caulobacter crescentus is an aerobic bacterium that is
      highly resistant to uranium (U) and has great potential to be used in U
      bioremediation, but its mechanisms of U resistance are poorly understood. We
      conducted a Tn-seq screen to identify genes specifically required for U
      resistance in C. crescentus. The genes that we identified have previously
      remained elusive using other omics approaches and thus provide significant
      insight into the mechanisms of U resistance by C. crescentus. In particular, we
      show that outer membrane transporters RsaFa and RsaFb, previously known as part
      of the S-layer export machinery, may confer U resistance by U efflux and/or by
      maintaining membrane integrity during U stress.

PMID- 26195599
TI  - Binding of Cyclic Di-AMP to the Staphylococcus aureus Sensor Kinase KdpD Occurs
      via the Universal Stress Protein Domain and Downregulates the Expression of the
      Kdp Potassium Transporter.
AB  - Nucleotide signaling molecules are important intracellular messengers that
      regulate a wide range of biological functions. The human pathogen Staphylococcus
      aureus produces the signaling nucleotide cyclic di-AMP (c-di-AMP). This molecule
      is common among Gram-positive bacteria and in many organisms is essential for
      survival under standard laboratory growth conditions. In this study, we
      investigated the interaction of c-di-AMP with the S. aureus KdpD protein. The
      sensor kinase KdpD forms a two-component signaling system with the response
      regulator KdpE and regulates the expression of the kdpDE genes and the kdpFABC
      operon coding for the Kdp potassium transporter components. Here we show that the
      S. aureus KdpD protein binds c-di-AMP specifically and with an affinity in the
      micromolar range through its universal stress protein (USP) domain. This domain
      is located within the N-terminal cytoplasmic region of KdpD, and amino acids of a
      conserved SXS-X20-FTAXY motif are important for this binding. We further show
      that KdpD2, a second KdpD protein found in some S. aureus strains, also binds c
      di-AMP, and our bioinformatics analysis indicates that a subclass of KdpD
      proteins in c-di-AMP-producing bacteria has evolved to bind this signaling
      nucleotide. Finally, we show that c-di-AMP binding to KdpD inhibits the
      upregulation of the kdpFABC operon under salt stress, thus indicating that c-di
      AMP is a negative regulator of potassium uptake in S. aureus. IMPORTANCE:
      Staphylococcus aureus is an important human pathogen and a major cause of food
      poisoning in Western countries. A common method for food preservation is the use
      of salt to drive dehydration. This study sheds light on the regulation of
      potassium uptake in Staphylococcus aureus, an important aspect of this
      bacterium's ability to tolerate high levels of salt. We show that the signaling
      nucleotide c-di-AMP binds to a regulatory component of the Kdp potassium uptake
      system and that this binding has an inhibitory effect on the expression of the
      kdp genes encoding a potassium transporter. c-di-AMP binds to the USP domain of
      KdpD, thus providing for the first time evidence for the ability of such a domain
      to bind a cyclic dinucleotide.

PMID- 26195601
TI  - Diversity of freshwater Epsilonproteobacteria and dark inorganic carbon fixation
      in the sulphidic redoxcline of a meromictic karstic lake.
AB  - Sulfidic redoxclines are a suitable niche for the growth and activity of
      different chemo- and photolithotrophic sulphide-oxidizing microbial groups such
      as the Epsilonproteobacteria and the green sulfur bacteria (GSB). We have
      investigated the diversity, abundance and contribution to inorganic carbon uptake
      of Epsilonproteobacteria in a meromictic basin of Lake Banyoles. CARD-FISH counts
      revealed that Epsilonproteobacteria were prevalent at the redoxcline in winter
      (maximum abundance of 2 * 10(6) cells mL(-1), ~60% of total cells) but they were
      nearly absent in summer, when GSB bloomed. This seasonal trend was supported by
      16S rRNA gene pyrotag datasets, which revealed that the epsilonproteobacterial
      community was mainly composed of a member of the genus Arcobacter. In situ
      incubations using NaH(14)CO3 and MAR-CARD-FISH observations showed that this
      population assimilated CO2 in the dark, likely being mainly responsible for the
      autotrophic activity at the redoxcline in winter. Clone libraries targeting the
      aclB gene provided additional evidence of the potential capacity of these
      epsilonproteobacteria to fix carbon via rTCA cycle. Our data reinforce the key
      role of Epsilonproteobacteria in linking carbon and sulphur cycles, extend their
      influence to freshwater karstic lakes and raise questions about the actual
      contribution of chemolithotrophy at their redoxcline and euxinic water
      compartments. 

PMID- 26195602
TI  - Governing Health Care through Free Choice: Neoliberal Reforms in Denmark and the
      United States.
AB  - We compare free choice reforms in Denmark and the United States to understand
      what ideas and political forces could generate such similar policy reforms in
      radically different political contexts. We analyze the two cases using our own
      interpretation of neoliberalism as having "two faces." The first face seeks to
      expand private markets and shrink the public sector; the second face seeks to
      strengthen the public sector's capacity to govern through incentives and
      competition. First, we show why these two most-different cases offer a useful
      comparison to understand similar policy tools. Second, we develop our theoretical
      framework of the two faces of neoliberalism. Third, we examine Denmark's
      introduction of a free choice of hospitals in 2002, a policy that for the first
      time allowed some patients to receive care either in a public hospital outside
      their local area or in a private hospital. Fourth, we examine the introduction of
      free choice among private managed care plans into the US Medicare program in
      1997. We show how policy makers in both countries used neoliberal reform as a
      mechanism to make their public health care sectors governable. Fifth, on the
      basis of our analysis, we draw five lessons about neoliberal policy reforms. 

PMID- 26195600
TI  - The enrichment of an alkaliphilic biofilm consortia capable of the anaerobic
      degradation of isosaccharinic acid from cellulosic materials incubated within an
      anthropogenic, hyperalkaline environment.
AB  - Anthropogenic hyperalkaline sites provide an environment that is analogous to
      proposed cementitious geological disposal facilities (GDF) for radioactive waste.
      Under anoxic, alkaline conditions cellulosic wastes will hydrolyze to a range of
      cellulose degradation products (CDP) dominated by isosaccharinic acids (ISA). In
      order to investigate the potential for microbial activity in a cementitious GDF,
      cellulose samples were incubated in the alkaline (~pH 12), anaerobic zone of a
      lime kiln waste site. Following retrieval, these samples had undergone partial
      alkaline hydrolysis and were colonized by a Clostridia-dominated biofilm
      community, where hydrogenotrophic, alkaliphilic methanogens were also present.
      When these samples were used to establish an alkaline CDP fed microcosm, the
      community shifted away from Clostridia, methanogens became undetectable and a
      flocculate community dominated by Alishewanella sp. established. These flocs were
      composed of bacteria embedded in polysaccharides and proteins stabilized by
      extracellular DNA. This community was able to degrade all forms of ISA with >60%
      of the carbon flow being channelled into extracellular polymeric substance (EPS)
      production. This study demonstrated that alkaliphilic microbial communities can
      degrade the CDP associated with some radioactive waste disposal concepts at pH
      11. These communities divert significant amounts of degradable carbon to EPS
      formation, suggesting that EPS has a central role in the protection of these
      communities from hyperalkaline conditions. 

PMID- 26195603
TI  - The Impact of the ACA on Premiums: Evidence from the Self-Employed.
AB  - This article examines the impact of the Affordable Care Act on premiums by
      studying a segment of the nongroup market, the self-employed. Because self
      employed health insurance premiums are deductible, tax data contain comprehensive
      individual-level information on the premiums paid by this group prior to the
      establishment of health insurance exchanges. We compare these prior premiums to
      reference silver premiums available on the exchanges and find that exchange
      premiums are 4.2 percent higher on average among the entire sample but 42.3
      percent lower on average after taxes and subsidies. We also examine which type of
      exchange coverage would cost less than the individual's prior health insurance
      premiums and find that almost 60 percent of families could purchase bronze plans
      for less than their prior premiums, though only about a quarter could purchase
      platinum plans. After taxes and subsidies, the fractions increase to over 85
      percent for bronze plans and over half for platinum plans. 

PMID- 26195604
TI  - The Remarkable Staying Power of "Death Panels".
AB  - Sarah Palin's phrase "death panels" derailed proposed provisions of the
      Affordable Care Act (ACA) to pay physicians for end-of-life discussions with
      patients, a policy designed to make dying more humane, something all Americans
      desire. Even now, "death panels" has truth-value for approximately half of
      Americans and is used to paint ACA components as threatening to "pull the plug on
      Grandma." How can this be? To some, the death panels claim is simply a lie, an
      improvised explosive device hurled against any ACA provision. To others, the
      phrase's power stems from the public's lack of a common vocabulary to discuss end
      of-life care. "Death panels," however, taps into many Americans' fear of
      government involvement, that government's purchasing end-of-life discussions as
      commodities necessitates accountability and cost control. Standardization and
      reduction of humanity follows, something Americans already experience routinely
      in their health care system. Expert jargon, compelling among experts themselves,
      doesn't evoke people's images of chats with Marcus Welby. The jargon is
      unintelligible, off-putting. When that jargon enters the nonjargonized world, it
      mixes with common fears, extant experience of dehumanization and reduction, and
      awareness that someone's plug is getting pulled all the time. "Death panels"
      cannot be dismissed as delusional, but neither can it help fulfill Americans'
      aspirations for a humane last voyage. 

PMID- 26195605
TI  - Like Surfers Waiting for the Big Wave: Health Care Politics in Italy.
AB  - This article focuses on the main health reforms enacted in Italy over the past
      one hundred years. Such reforms were all undertaken in conjunction with a severe
      political and institutional crisis. The 1943 reform was approved a few weeks
      before the fall of the Fascist regime. The National Health Service, established
      by Law No. 833 of 1978 and enacted during one of the most turbulent times in the
      history of the country, represented the apex of the brief experience of the
      "national solidarity" governments. Even the 1992-93 reform was put into effect in
      the midst of the Tangentopoli scandal, which marked the transition from the First
      Republic to the so-called Second Republic. To attempt an analysis of the main
      turning points in Italian health care policies, the well-known multiple streams
      approach is adopted. 

PMID- 26195606
TI  - The Politics of Universal Health Coverage in Low- and Middle-Income Countries: A
      Framework for Evaluation and Action.
AB  - Universal health coverage has recently become a top item on the global health
      agenda pressed by multilateral and donor organizations, as disenchantment grows
      with vertical, disease-specific health programs. This increasing focus on
      universal health coverage has brought renewed attention to the role of domestic
      politics and the interaction between domestic and international relations in the
      health reform process. This article proposes a theory-based framework for
      analyzing the politics of health reform for universal health coverage, according
      to four stages in the policy cycle (agenda setting, design, adoption, and
      implementation) and four variables that affect reform (interests, institutions,
      ideas, and ideology). This framework can assist global health policy researchers,
      multilateral organization officials, and national policy makers in navigating the
      complex political waters of health reforms aimed at achieving universal health
      coverage. To derive the framework, we critically review the theoretical and
      applied literature on health policy reform in developing countries and illustrate
      the framework with examples of health reforms moving toward universal coverage in
      low- and middle-income countries. We offer a series of lessons stemming from
      these experiences to date. 

PMID- 26195607
TI  - Explaining Large-Scale Policy Change in the Turkish Health Care System: Ideas,
      Institutions, and Political Actors.
AB  - Explaining policy change has been one of the major concerns of the health care
      politics and policy development literature. This article aims to explain the
      specific dynamics of large-scale reforms introduced within the framework of the
      Health Transformation Program in Turkey. It argues that confluence of the three
      streams - problem, policy, and politics - with the exceptional political will of
      the Justice and Development Party's (JDP) leaders opened up a window of
      opportunity for a large-scale policy change. The article also underscores the
      contribution of recent ideational perspectives that help explain "why" political
      actors in Turkey would focus on health care reform, given that there are a number
      of issues waiting to be addressed in the policy agenda. Examining how political
      actors framed problems and policies deepens our understanding of the content of
      the reform initiatives as well as the construction of the need to reform. The
      article builds on the insights of both the ideational and institutionalist
      perspectives when it argues that the interests, aspirations, and fears of the
      JDP, alongside the peculiar characteristics of the institutional context, have
      shaped its priorities and determination to carry out this reform initiative.

PMID- 26195609
TI  - Foreword of the Commissioner and General Director of the Istituto Superiore di
      Sanita, Rome.

PMID- 26195610
TI  - Foreword of the President of the Associazione Nazionale Medici Cardiologi
      Ospedalieri, Florence.

PMID- 26195611
TI  - Foreword of the President of the Fondazione per il Tuo Cuore (Heart Care
      Foundation), Florence.

PMID- 26195614
TI  - Corrigendum to the clinical significance of below-knee great saphenous vein
      reflux following endovenous laser ablation of above-knee great saphenous vein.

PMID- 26195612
TI  - Cardiovascular health in Italy. Ten-year surveillance of cardiovascular diseases
      and risk factors: Osservatorio Epidemiologico Cardiovascolare/Health Examination
      Survey 1998-2012.
AB  - BACKGROUND: Surveillance of and monitoring trends for cardiovascular diseases and
      risk factors are relevant when we consider that these diseases and conditions are
      largely preventable. The aim of this paper is to assess time trends of
      cardiovascular diseases, lifestyles, risk factors and high risk conditions in
      different socioeconomic levels. METHODS: Paired but independent population
      samples of men and women aged 35-74 years located in all 20 Italian regions were
      examined in 1998-2002 (n = 9612) and in 2008-2012 (n = 8141). Time trends of
      lifestyles, cardiovascular risk factors, prevalence of high-risk conditions and
      cardiovascular diseases are shown for two different socioeconomic levels, as
      assessed by educational level. RESULTS: Over 10 years, in both genders and
      socioeconomic classes, the prevalence of smoking decreased (from 32% to 23% in
      men) as well as mean levels of blood pressure (systolic from 136 mmHg to 133 mmHg
      in men and from 132 mmHg to 127 mmHg in women), while the prevalence of
      dyslipidemia and obesity increased reaching 35% and 25% of the population
      respectively; the prevalence of myocardial infarction remained stable (1.6% in
      men; about 0.5% in women), that of stroke decreased in men (from 1.2% to 0.7%);
      the prevalence of diabetes did not change (12% in men; 8% in women). In the low
      educational class, cardiovascular risk factors and diseases remained unfavourable
      compared with the high educational class. CONCLUSIONS: The burden of
      cardiovascular diseases and their risk factors remain high and require continuous
      appropriate action at the community and individual levels, as suggested by the
      European Guidelines for Cardiovascular Prevention.

PMID- 26195615
TI  - Sample size adjustment based on promising interim results and its application in
      confirmatory clinical trials.
AB  - BACKGROUND: For a carefully planned and well-designed Phase 3 confirmatory trial,
      there is still a potential risk of failing to meet the study objective due to
      possible differences between Phase 2 and Phase 3 studies. As illustrated by the
      ENGAGE trial, potential sample size increase at an interim analysis can mitigate
      the risk for an otherwise underpowered study. Many approaches for sample size
      adjustment (SSA) require certain modifications to the conventional statistical
      method, such as changing critical values or using a weighted Z-statistic for
      final hypothesis testing. Without modification, the type I error rate can be
      inflated, primarily caused by sample size increase for nonpromising interim
      observation that is close to null or no treatment effect. As illustrated by the
      TOPICAL trial, increasing sample size for nonpromising interim result could waste
      limited resource on ineffective treatment. The modifications in these approaches
      are therefore unnecessary costs of flexibility/interpretability for unnecessary
      scenarios of sample size increase. PURPOSE: To discuss and illustrate the
      appropriateness of SSA based on promising interim results, that is, conditional
      power being greater than 50% (or CDL approach), in a carefully planned and well
      designed Phase 3 confirmatory trial. METHODS: Two clinical trials are used to
      illustrate the clinical setting for the CDL approach and appropriateness of its
      application. Operating characteristics are assessed and compared to other methods
      using numeric computation. Hypothetical trials based on real clinical data are
      used to illustrate the approach. RESULTS: The CDL approach for SSA leads to a
      small increase in expected sample size resulting in a small power gain versus the
      fixed design. This indicates that adding SSA will not on average substantially
      affect the budget at the portfolio level. However, when the interim result is
      promising, the CDL approach can dramatically increase the conditional power
      therefore mitigating the risk of an otherwise underpowered study. LIMITATIONS:
      Implementation challenges of the SSA methods are not in the scope of this paper.
      SSA is not intended to replace careful design of a confirmatory trial; instead,
      it can mitigate the risk for a well-designed trial. CONCLUSIONS: The CDL approach
      for SSA based on promising interim results, that is, conditional power being
      greater than 50%, is particularly useful in mitigating the risk for a carefully
      planned and well-designed Phase 3 confirmatory trial. No modification to the
      conventional statistical procedure is necessary while the type I error rate is
      controlled. Such a feature of ''no interference,'' or no change to the
      conventional statistical procedure with or without sample size adjustment, is
      important for the interpretation of a confirmatory trial. Similar to the fixed
      design, carefully planned and well-designed group sequential studies can also
      benefit from SSA to mitigate the risk of failing to meet the study objective.

PMID- 26195616
TI  - How bacteria maintain location and number of flagella?
AB  - Bacteria differ in number and location of their flagella that appear in regular
      patterns at the cell surface (flagellation pattern). Despite the plethora of
      bacterial species, only a handful of these patterns exist. The correct
      flagellation pattern is a prerequisite for motility, but also relates to biofilm
      formation and the pathogenicity of disease-causing flagellated bacteria. However,
      the mechanisms that maintain location and number of flagella are far from being
      understood. Here, we review our knowledge on mechanisms that enable bacteria to
      maintain their appropriate flagellation pattern. While some peritrichous
      flagellation patterns might occur by rather simple stochastic processes, other
      bacterial species appear to rely on landmark systems to define the designated
      flagellar position. Such landmarks are the Tip system of Caulobacter crescentus
      or the signal recognition particle (SRP)-GTPase FlhF and the MinD/ParA-type
      ATPase FlhG (synonyms: FleN, YlxH and MinD2). The latter two proteins constitute
      a regulatory circuit essential for diverse flagellation patterns in many Gram
      positive and negative species. The interactome of FlhF/G (e.g. C-ring proteins
      FliM, FliN, FliY or the transcriptional regulator FleQ/FlrA) seems evolutionary
      adapted to meet the specific needs for a respective pattern. This variability
      highlights the importance of the correct flagellation pattern for motile species.

PMID- 26195617
TI  - Review of current methods for characterizing virulence and pathogenicity
      potential of industrial Saccharomyces cerevisiae strains towards humans.
AB  - Most industrial Saccharomyces cerevisiae strains used in food or biotechnology
      processes are benign. However, reports of S. cerevisiae infections have emerged
      and novel strains continue to be developed. In order to develop recommendations
      for the human health risk assessment of S. cerevisiae strains, we conducted a
      literature review of current methods used to characterize their pathogenic
      potential and evaluated their relevance towards risk assessment. These studies
      revealed that expression of virulence traits in S. cerevisiae is complex and
      depends on many factors. Given the opportunistic nature of this organism, an
      approach using multiple lines of evidence is likely necessary for the reasonable
      prediction of the pathogenic potential of a particular strain. Risk assessment of
      S. cerevisiae strains would benefit from more research towards the comparison of
      virulent and non-virulent strains in order to better understand those genotypic
      and phenotypic traits most likely to be associated with pathogenicity. 

PMID- 26195618
TI  - The physiological cost index of walking with a powered knee-ankle-foot orthosis
      in subjects with poliomyelitis: A pilot study.
AB  - BACKGROUND: A powered knee-ankle-foot orthosis was developed to provide
      restriction of knee flexion during stance phase and active flexion and extension
      of the knee during swing phase of gait. OBJECTIVE: The purpose of this study was
      to determine its effect on the physiological cost index, walking speed and the
      distance walked in people with poliomyelitis compared to when walking with a knee
      ankle-foot orthosis with drop lock knee joints. STUDY DESIGN: Quasi experimental
      study. METHODS: Seven subjects with poliomyelitis volunteered for the study and
      undertook gait analysis with both types of knee-ankle-foot orthosis. RESULTS:
      Walking with the powered knee-ankle-foot orthosis significantly reduced walking
      speed (p = 0.015) and the distance walked (p = 0.004), and also, it did not
      improve physiological cost index values (p = 0.009) compared to walking with the
      locked knee-ankle-foot orthosis. CONCLUSION: Using a powered knee-ankle-foot
      orthosis did not significantly improve any of the primary outcome measures during
      walking for poliomyelitis subjects. CLINICAL RELEVANCE: This powered knee-ankle
      foot orthosis design did not improve the physiological cost index of walking for
      people with poliomyelitis when compared to walking with a knee-ankle-foot
      orthosis with drop lock knee joints. This may have been due to the short training
      period used or the bulky design and additional weight of the powered orthosis.
      Further research is therefore warranted.

PMID- 26195619
TI  - Comparison of the efficacy of a neutral wrist splint and a wrist splint
      incorporating a lumbrical unit for the treatment of patients with carpal tunnel
      syndrome.
AB  - BACKGROUND: Different types of splints have been used as a conservative
      intervention to improve symptoms in patients with Carpal tunnel syndrome (CTS).
      Although a number of studies have been undertaken to compare different splints,
      information and understanding of the influence of these interventions are
      lacking. OBJECTIVES: The purpose of this study was to compare the effect of a
      classic thermoplastic wrist splint or a wrist splint with an additional
      metacarpophalangeal unit on pain, function, grip strength, and pinch strength in
      patients with mild-to-moderate carpal tunnel syndrome. STUDY DESIGN: Quasi
      experimental design. METHODS: A total of 24 patients received conservative
      treatment using either the classic wrist splint or the wrist splint with the
      metacarpophalangeal unit for a period of 6 weeks. Primary outcome measures were
      pain, function, grip strength, and pinch strength. Data were collected
      immediately before and after using the two types of splints at baseline (0 weeks)
      and 6 weeks. Statistical analysis was performed using the paired t-test and an
      independent t-test. RESULTS: Compared to baseline, both the classic thermoplastic
      wrist splint and the wrist splint with a metacarpophalangeal unit significantly
      decreased pain and increased function, pinch strength, and grip strength.
      Comparisons of the two types of splints for grip strength (P = 0.675) and pinch
      strength (P = 0.650) revealed that there were no significant differences between
      the two after 6 weeks of wear. However, there were significant differences in
      pain levels (P = 0.022) and the Disability of the Arm, Shoulder, and Hand score
      (P = 0.027) between the two types of splints from baseline to 6 weeks.
      CONCLUSION: The wrist splint with a metacarpophalangeal unit was more effective
      than the classic thermoplastic wrist splint in pain reduction and improvement of
      function. CLINICAL RELEVANCE: A wrist splint with a metacarpophalangeal unit may
      be an appropriate conservative treatment in the rehabilitation of patients with
      mild-to-moderate carpal tunnel syndrome.

PMID- 26195620
TI  - Comparison of gait between healthy participants and persons with spinal cord
      injury when using the advanced reciprocating gait orthosis.
AB  - BACKGROUND: The advanced reciprocating gait orthosis (ARGO) has a rigid structure
      which provides restricted movement at the hip, knee, and ankle joints and
      incorporates a pelvic section with an extended section in the lumbar region.
      Healthy subjects, when walking with an RGO in situ, could feasibly demonstrate
      the level of limitation in movement imposed by ARGO-assisted ambulation.
      OBJECTIVE: The aim of this study was to compare the function of the advanced
      reciprocating gait orthosis when fitted with the dorsiflexion-assist ankle-foot
      orthoses on temporal-spatial parameters and kinematics of walking in both able
      bodied people and those with spinal cord injury. STUDY DESIGN: Quasi experimental
      design. METHODS: Data were acquired from six able-bodied and four spinal cord
      injury subjects who used an advanced reciprocating gait orthosis which
      incorporated dorsiflexion-assist ankle-foot orthoses. Kinematics and temporal
      spatial parameters were calculated and compared. RESULTS: All able-bodied
      individuals walked with speeds which were only approximately one-third that of
      when walking without an orthosis. The mean step length and cadence were both
      reduced by 48% and 6%, respectively. There were significant differences in hip,
      knee, and ankle joint range of motions between normal walking and walking with
      the advanced reciprocating gait orthosis both in able-bodied subjects and
      patients with spinal cord injury. There were also significant differences in the
      speed of walking, cadence, step length, hip range of motion, and ankle range of
      motion when using the advanced reciprocating gait orthosis between the two
      groups. CONCLUSION: Temporal-spatial parameters and lower limb sagittal plane
      kinematics of walking were altered compared to normal walking, especially when
      spinal cord injury subjects walked with the advanced reciprocating gait orthosis
      compared to the able-bodied subjects. CLINICAL RELEVANCE: To produce an
      improvement in RGO function, an increase in walking performance should involve
      attention to improvement of hip, knee, and ankle joint kinematics, which differs
      significantly from normal walking.

PMID- 26195621
TI  - Functional effects of a prosthetic torsion adapter in trans-tibial amputees
      during unplanned spin and step turns.
AB  - BACKGROUND: Shear stress at the stump in trans-tibial amputees induced by turning
      movements may be reduced with the use of torsion adapters in the prosthesis.
      OBJECTIVE: Monitoring the motion and kinetic effects of a regular torsion adapter
      in comparison to a rigid placebo in unplanned spin and step turns. STUDY DESIGN:
      Single-blinded placebo-controlled cohort study. METHODS: In total, 10 trans
      tibial amputees underwent three-dimensional gait analysis in level walking and
      unplanned spin and step turns with a torsion adapter and with a rigid placebo.
      RESULTS: Kinetic effects varied among participants. No statistically significant
      reduction of peak internal and peak external transverse plane moments was found
      for the torsion adapter in any walking condition. However, transverse plane
      rotation of the adapter was monitored in all participants. CONCLUSION: Motion
      between the socket and the residual limb may be reduced during turns due to
      transverse plane motion of the torsion adapter and shear stress on the residual
      limb may be reduced. However, there may be good and bad responders to torsion
      adapters due to differences in coupling between the residual limb and the socket.
      CLINICAL RELEVANCE: Strong coupling between stump and socket will help the user
      controlling his prosthesis. Shear stress at the stump may increase in stump
      socket interface stiffness and may be the reason for residual limb problems.
      Torsion adapters therefore may be beneficial for comfort and stump condition in
      individual cases.

PMID- 26195622
TI  - Experience of training in communication skills among trainee neonatologists.

PMID- 26195623
TI  - The blue accessory digit.

PMID- 26195624
TI  - Antenatal factors modulate hearing screen failure risk in preterm infants.
AB  - OBJECTIVE: The objective of this study was to characterise the effects of
      antenatal inflammatory factors and maternal therapies on neonatal hearing screen
      outcomes in very low birthweight infants. METHODS: We conducted a retrospective
      study of a cohort of infants <33 weeks' gestational age and <1501 g birth weight
      prospectively enrolled between 1999 and 2003 for whom placental pathology, cord
      blood interleukin (IL) 6, IL-1beta, tumour necrosis factor-alpha and neonatal
      hearing screen results were available. RESULTS: Of 289 infants with documented
      hearing screen results, 244 (84%) passed and 45 (16%) failed the hearing screen
      (unilateral, N=25 (56%); bilateral, N=20 (44%)). In the final logistic model, the
      fetal inflammatory response syndrome defined as the presence of fetal vasculitis
      and/or cord serum IL-6>18.2 pg/mL was the factor with greatest risk for hearing
      screen failure (OR 3.62, 95% CI 1.38 to 9.5). A patent ductus arteriosus treated
      with indomethacin significantly increased the risk (OR 3.3, 95% CI 1.3 to 8.26),
      while combined maternal steroid and magnesium sulfate exposure (0.37, 95% CI 0.11
      to 0.81) reduced the risk for hearing screen failure. CONCLUSIONS: Intrauterine
      infection with a fetal inflammatory response is a risk factor for neonatal
      hearing loss while maternal therapies significantly reduced the risk of neonatal
      hearing loss in very low birthweight infants.

PMID- 26195625
TI  - Some "Thing" to Talk About? Differential Story Utility From Experiential and
      Material Purchases.
AB  - Psychological research has shown that experiential purchases (a hike in the
      woods, a trip to Rome) bring more happiness than material purchases (a designer
      shirt, a flat-screen television). The research presented in this article
      investigates one cause and consequence of this difference: People talk more about
      their experiences than their possessions and derive more value from doing so. A
      series of eight studies demonstrate that taking away the ability to talk about
      experiences (but not material goods) would diminish the enjoyment they bring;
      that people believe they derive more happiness from talking about experiential
      purchases; that when given a choice about which of their purchases to talk about,
      people are more likely to talk about experiential rather than material
      consumption; and that people report being more inclined to talk about their
      experiences than their material purchases and derive more hedonic benefits as a
      result--both in prospect and in retrospect.

PMID- 26195626
TI  - Mimicry Is Presidential: Linguistic Style Matching in Presidential Debates and
      Improved Polling Numbers.
AB  - The current research used the contexts of U.S. presidential debates and
      negotiations to examine whether matching the linguistic style of an opponent in a
      two-party exchange affects the reactions of third-party observers. Building off
      communication accommodation theory (CAT), interaction alignment theory (IAT), and
      processing fluency, we propose that language style matching (LSM) will improve
      subsequent third-party evaluations because matching an opponent's linguistic
      style reflects greater perspective taking and will make one's arguments easier to
      process. In contrast, research on status inferences predicts that LSM will
      negatively impact third-party evaluations because LSM implies followership. We
      conduct two studies to test these competing hypotheses. Study 1 analyzed
      transcripts of U.S. presidential debates between 1976 and 2012 and found that
      candidates who matched their opponent's linguistic style increased their standing
      in the polls. Study 2 demonstrated a causal relationship between LSM and third
      party observer evaluations using negotiation transcripts. 

PMID- 26195627
TI  - Analysis of Conserved Glutamate and Aspartate Residues in Drosophila Rhodopsin 1
      and Their Influence on Spectral Tuning.
AB  - The molecular mechanisms that regulate invertebrate visual pigment absorption are
      poorly understood. Studies of amphioxus Go-opsin have demonstrated that Glu-181
      functions as the counterion in this pigment. This finding has led to the proposal
      that Glu-181 may function as the counterion in other invertebrate visual pigments
      as well. Here we describe a series of mutagenesis experiments to test this
      hypothesis and to also test whether other conserved acidic amino acids in
      Drosophila Rhodopsin 1 (Rh1) may serve as the counterion of this visual pigment.
      Of the 5 Glu and Asp residues replaced by Gln or Asn in our experiments, none of
      the mutant pigments shift the absorption of Rh1 by more than 6 nm. In combination
      with prior studies, these results suggest that the counterion in Drosophila Rh1
      may not be located at Glu-181 as in amphioxus, or at Glu-113 as in bovine
      rhodopsin. Conversely, the extremely low steady state levels of the E194Q mutant
      pigment (bovine opsin site Glu-181), and the rhabdomere degeneration observed in
      flies expressing this mutant demonstrate that a negatively charged residue at
      this position is essential for normal rhodopsin function in vivo. This work also
      raises the possibility that another residue or physiologic anion may compensate
      for the missing counterion in the E194Q mutant.

PMID- 26195628
TI  - Heme and I.

PMID- 26195629
TI  - A Role for Autoinhibition in Preventing Dimerization of the Transcription Factor
      ETS1.
AB  - ETS1 is the archetype of the ETS transcription factor (TF) family. ETS TFs share
      a DNA-binding domain, the ETS domain. All ETS TFs recognize a core GGA(A/T)
      binding site, and thus ETS TFs are found to redundantly regulate the same genes.
      However, each ETS TF has unique targets as well. One prevailing hypotheses
      explaining this duality is that protein-protein interactions, including
      homodimerization, allow each ETS TF to display distinct behavior. The behavior of
      ETS1 is further regulated by autoinhibition. Autoinhibition apparently modulates
      ETS1 DNA binding affinity, but the mechanism of this inhibition is not completely
      understood. We sought to characterize the relationship between DNA binding and
      ETS1 homodimer formation. We find that ETS1 interrogates DNA and forms dimers
      even when the DNA does not contain an ETS recognition sequence. Mutational
      studies also link nonspecific DNA backbone contacts with dimer formation, in
      addition to providing a new role for the recognition helix of ETS1 in maintaining
      the autoinhibited state. Finally, in showing that residues in the DNA recognition
      helix affect autoinhibition, we define a new function of ETS1 autoinhibition:
      maintenance of a monomeric state in the absence of DNA. The conservation of
      relevant amino acid residues across all ETS TFs indicates that the mechanisms of
      nonspecific DNA interrogation and protein oligomer formation elucidated here may
      be common to all ETS proteins that autoinhibit. 

PMID- 26195630
TI  - Plasma Membrane Tetraspanin CD81 Complexes with Proprotein Convertase
      Subtilisin/Kexin Type 9 (PCSK9) and Low Density Lipoprotein Receptor (LDLR), and
      Its Levels Are Reduced by PCSK9.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important factor in
      plasma cholesterol regulation through modulation of low density lipoprotein
      receptor (LDLR) levels. Naturally occurring mutations can lead to hyper- or
      hypocholesterolemia in human. Recently, we reported that PCSK9 was also able to
      modulate CD81 in Huh7 cells. In the present study, several gain-of-function and
      loss-of-function mutants as well as engineered mutants of PCSK9 were compared for
      their ability to modulate the cell surface expression of LDLR and CD81. Although
      PCSK9 gain-of-function D374Y enhanced the degradation both receptors, D374H and
      D129N seemed to only reduce LDLR levels. In contrast, mutations in the C-terminal
      hinge-cysteine-histidine-rich domain segment primarily affected the PCSK9-induced
      CD81 degradation. Furthermore, when C-terminally fused to an ACE2 transmembrane
      anchor, the secretory N-terminal catalytic or hinge-cysteine-histidine-rich
      domain domains of PCSK9 were able to reduce CD81 and LDLR levels. These data
      confirm that PCSK9 reduces CD81 levels via an intracellular pathway as reported
      for LDLR. Using immunocytochemistry, a proximity ligation assay, and co
      immunoprecipitation, we found that the cell surface level of PCSK9 was enhanced
      upon overexpression of CD81 and that both PCSK9 and LDLR interact with this
      tetraspanin protein. Interestingly, using CHO-A7 cells lacking LDLR expression,
      we revealed that LDLR was not required for the degradation of CD81 by PCSK9, but
      its presence strengthened the PCSK9 effect. 

PMID- 26195631
TI  - Bone Cell-autonomous Contribution of Type 2 Cannabinoid Receptor to Breast Cancer
      induced Osteolysis.
AB  - The cannabinoid type 2 receptor (CB2) has previously been implicated as a
      regulator of tumor growth, bone remodeling, and bone pain. However, very little
      is known about the role of the skeletal CB2 receptor in the regulation of
      osteoblasts and osteoclasts changes associated with breast cancer. Here we found
      that the CB2-selective agonists HU308 and JWH133 reduced the viability of a
      variety of parental and bone-tropic human and mouse breast cancer cells at high
      micromolar concentrations. Under conditions in which these ligands are used at
      the nanomolar range, HU308 and JWH133 enhanced human and mouse breast cancer cell
      induced osteoclastogenesis and exacerbated osteolysis, and these effects were
      attenuated in cultures obtained from CB2-deficient mice or in the presence of a
      CB2 receptor blocker. HU308 and JWH133 had no effects on osteoblast growth or
      differentiation in the presence of conditioned medium from breast cancer cells,
      but under these circumstances both agents enhanced parathyroid hormone-induced
      osteoblast differentiation and the ability to support osteoclast formation.
      Mechanistic studies in osteoclast precursors and osteoblasts showed that JWH133
      and HU308 induced PI3K/AKT activity in a CB2-dependent manner, and these effects
      were enhanced in the presence of osteolytic and osteoblastic factors such as
      RANKL (receptor activator of NFkappaB ligand) and parathyroid hormone. When
      combined with published work, these findings suggest that breast cancer and bone
      cells exhibit differential responses to treatment with CB2 ligands depending upon
      cell type and concentration used. We, therefore, conclude that both CB2-selective
      activation and antagonism have potential efficacy in cancer-associated bone
      disease, but further studies are warranted and ongoing. 

PMID- 26195632
TI  - Aggregation of Polyglutamine-expanded Ataxin 7 Protein Specifically Sequesters
      Ubiquitin-specific Protease 22 and Deteriorates Its Deubiquitinating Function in
      the Spt-Ada-Gcn5-Acetyltransferase (SAGA) Complex.
AB  - Human ataxin 7 (Atx7) is a component of the deubiquitination module (DUBm) in the
      Spt-Ada-Gcn5-acetyltransferase (SAGA) complex for transcriptional regulation, and
      expansion of its polyglutamine (polyQ) tract leads to spinocerebellar ataxia type
      7. However, how polyQ expansion of Atx7 affects DUBm function remains elusive. We
      investigated the effects of polyQ-expanded Atx7 on ubiquitin-specific protease
      (USP22), an interacting partner of Atx7 functioning in deubiquitination of
      histone H2B. The results showed that the inclusions or aggregates formed by polyQ
      expanded Atx7 specifically sequester USP22 through their interactions mediated by
      the N-terminal zinc finger domain of Atx7. The mutation of the zinc finger domain
      in Atx7 that disrupts its interaction with USP22 dramatically abolishes
      sequestration of USP22. Moreover, polyQ expansion of Atx7 decreases the
      deubiquitinating activity of USP22 and, consequently, increases the level of
      monoubiquitinated H2B. Therefore, we propose that polyQ-expanded Atx7 forms
      insoluble aggregates that sequester USP22 into a catalytically inactive state,
      and then the impaired DUBm loses the function to deubiquitinate monoubiquitinated
      histone H2B or H2A. This may result in dysfunction of the SAGA complex and
      transcriptional dysregulation in spinocerebellar ataxia type 7 disease. 

PMID- 26195633
TI  - The Yeast Nbp35-Cfd1 Cytosolic Iron-Sulfur Cluster Scaffold Is an ATPase.
AB  - Nbp35 and Cfd1 are prototypical members of the MRP/Nbp35 class of iron-sulfur
      (FeS) cluster scaffolds that function to assemble nascent FeS clusters for
      transfer to FeS-requiring enzymes. Both proteins contain a conserved NTPase
      domain that genetic studies have demonstrated is essential for their cluster
      assembly activity inside the cell. It was recently reported that these proteins
      possess no or very low nucleotide hydrolysis activity in vitro, and thus the role
      of the NTPase domain in cluster biogenesis has remained uncertain. We have
      reexamined the NTPase activity of Nbp35, Cfd1, and their complex. Using in vitro
      assays and site-directed mutagenesis, we demonstrate that the Nbp35 homodimer and
      the Nbp35-Cfd1 heterodimer are ATPases, whereas the Cfd1 homodimer exhibited no
      or very low ATPase activity. We ruled out the possibility that the observed ATP
      hydrolysis activity might result from a contaminating ATPase by showing that
      mutation of key active site residues reduced activity to background levels.
      Finally, we demonstrate that the fluorescent ATP analog 2'/3'-O-(N'
      methylanthraniloyl)-ATP (mantATP) binds stoichiometrically to Nbp35 with a KD =
      15.6 MUM and that an Nbp35 mutant deficient in ATP hydrolysis activity also
      displays an increased KD for mantATP. Together, our results demonstrate that the
      cytosolic iron-sulfur cluster assembly scaffold is an ATPase and pave the way for
      interrogating the role of nucleotide hydrolysis in cluster biogenesis by this
      large family of cluster scaffolding proteins found across all domains of life.

PMID- 26195634
TI  - Chlamydia trachomatis Scavenges Host Fatty Acids for Phospholipid Synthesis via
      an Acyl-Acyl Carrier Protein Synthetase.
AB  - The obligate intracellular parasite Chlamydia trachomatis has a reduced genome
      but relies on de novo fatty acid and phospholipid biosynthesis to produce its
      membrane phospholipids. Lipidomic analyses showed that 8% of the phospholipid
      molecular species synthesized by C. trachomatis contained oleic acid, an abundant
      host fatty acid that cannot be made by the bacterium. Mass tracing experiments
      showed that isotopically labeled palmitic, myristic, and lauric acids added to
      the medium were incorporated into C. trachomatis-derived phospholipid molecular
      species. HeLa cells did not elongate lauric acid, but infected HeLa cell cultures
      elongated laurate to myristate and palmitate. The elongated fatty acids were
      incorporated exclusively into C. trachomatis-produced phospholipid molecular
      species. C. trachomatis has adjacent genes encoding the separate domains of the
      bifunctional acyl-acyl carrier protein (ACP) synthetase/2
      acylglycerolphosphoethanolamine acyltransferase gene (aas) of Escherichia coli.
      The CT775 gene encodes an acyltransferase (LpaT) that selectively transfers fatty
      acids from acyl-ACP to the 1-position of 2-acyl-glycerophospholipids. The CT776
      gene encodes an acyl-ACP synthetase (AasC) with a substrate preference for
      palmitic compared with oleic acid in vitro. Exogenous fatty acids were elongated
      and incorporated into phospholipids by Escherichia coli-expressing AasC,
      illustrating its function as an acyl-ACP synthetase in vivo. These data point to
      an AasC-dependent pathway in C. trachomatis that selectively scavenges host
      saturated fatty acids to be used for the de novo synthesis of its membrane
      constituents.

PMID- 26195636
TI  - Concept-Based Word Learning in Human Infants.
AB  - Whether infants initially learn object labels by mapping them onto similarity
      defining perceptual features or onto concepts of object kinds remains under
      debate. We addressed this question by attempting to teach infants words for
      behaviorally defined action roles. In a series of experiments, we found that 14
      month-olds could rapidly learn a label for the role played by the chaser in a
      chasing scenario, even when the different instances of chasers did not share
      perceptual features. Furthermore, when infants could choose, they preferred to
      interpret a novel label as expressing the agent's role within the observed
      interaction rather than as being associated with the agent's appearance. These
      results demonstrate that infants can learn labels as easily (or even more easily)
      for concepts identified by abstract behavioral characteristics as for objects
      identified by perceptual features. Thus, at early stages of word learning,
      infants already expect that novel words express concepts. 

PMID- 26195635
TI  - Stanniocalcin-1 Potently Inhibits the Proteolytic Activity of the
      Metalloproteinase Pregnancy-associated Plasma Protein-A.
AB  - Stanniocalcin-1 (STC1) is a disulfide-bound homodimeric glycoprotein, first
      identified as a hypocalcemic hormone important for maintaining calcium
      homeostasis in teleost fish. STC1 was later found to be widely expressed in
      mammals, although it is not believed to function in systemic calcium regulation
      in these species. Several physiological functions of STC1 have been reported,
      although many molecular details are still lacking. We here demonstrate that STC1
      is an inhibitor of the metzincin metalloproteinase, pregnancy-associated plasma
      protein-A (PAPP-A), which modulates insulin-like growth factor (IGF) signaling
      through proteolytic cleavage of IGF-binding proteins (IGFBPs). STC1 potently (Ki
      = 68 pm) inhibits PAPP-A cleavage of IGFBP-4, and we show in a cell-based assay
      that STC1 effectively antagonizes PAPP-A-mediated type 1 IGF receptor (IGF1R)
      phosphorylation. It has recently been found that the homologous STC2 inhibits
      PAPP-A proteolytic activity, and that this depends on the formation of a covalent
      complex between the inhibitor and the proteinase, mediated by Cys-120 of STC2. We
      find that STC1 is unable to bind covalently to PAPP-A, in agreement with the
      absence of a corresponding cysteine residue. It rather binds to PAPP-A with high
      affinity (KD = 75 pm). We further demonstrate that both STC1 and STC2 show
      inhibitory activity toward PAPP-A2, but not selected serine proteinases and
      metalloproteinases. We therefore conclude that the STCs are proteinase
      inhibitors, probably restricted in specificity to the pappalysin family of
      metzincin metalloproteinases. Our data are the first to identify STC1 as a
      proteinase inhibitor, suggesting a previously unrecognized function of STC1 in
      the IGF system. 

PMID- 26195637
TI  - Photo Quiz: High Fevers in the High Desert in Oregon.

PMID- 26195638
TI  - An Obituary for the Case Report in Journal of Clinical Microbiology.

PMID- 26195639
TI  - Correction for Kondas et al., Variola Virus-Specific Diagnostic Assays:
      Characterization, Sensitivity, and Specificity.

PMID- 26195642
TI  - Cangrelor approved for use during coronary angioplasty.

PMID- 26195644
TI  - FDA continues work in identifying substances appropriate for compounding.

PMID- 26195646
TI  - Implementation of a national, Web-based critical care pharmacy journal club.

PMID- 26195647
TI  - Vitamin D overdosage in an infant from nonprescription vitamin D drops.

PMID- 26195648
TI  - Demonstrating the true value of antimicrobial stewardship programs.

PMID- 26195649
TI  - Systematic approach to antimicrobial restriction.

PMID- 26195650
TI  - Utilizing pharmacy students in transitions-of-care services.

PMID- 26195651
TI  - Respecting the risks of sterile compounding.

PMID- 26195652
TI  - Vedolizumab: An integrin-receptor antagonist for treatment of Crohn's disease and
      ulcerative colitis.
AB  - PURPOSE: The pharmacology, pharmacokinetics, safety, efficacy, and dosing
      recommendations of vedolizumab, an integrin-receptor antagonist for the treatment
      of Crohn's disease (CD) and ulcerative colitis (UC), are reviewed. SUMMARY:
      Vedolizumab is an integrin-receptor antagonist for the treatment of CD and UC in
      adults with moderately to severely active disease who have had an inadequate
      response with, lost response to, or were intolerant to anti-tumor necrosis factor
      (TNF) agents or immunomodulators or had an inadequate response with, were
      intolerant to, or demonstrated dependence on corticosteroids. Phase III clinical
      trials have demonstrated efficacy in achieving remission as induction and
      maintenance therapy in CD and UC. Remission was also achieved at week 10 in
      patients with CD in whom previous treatment with anti-TNF agents had failed.
      Adverse effects of vedolizumab include nasopharyngitis, headache, arthralgia,
      nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis,
      influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in
      the extremities. To date, no cases of progressive multifocal leukoencephalopathy
      (PML) have been reported. The recommended dose of vedolizumab in adults with UC
      or CD is 300 mg administered via intravenous infusion at zero, two, and six
      weeks, followed by every eight weeks. The average wholesale unit price is
      $5782.80, but a patient assistance program is available. CONCLUSION: Vedolizumab
      is a new alternative for patients with moderate-to-severe UC or CD, as well as
      patients who have not responded to anti-TNF agents. The current safety profile
      and lack of reported PML make it a promising addition to the treatment of these
      conditions.

PMID- 26195653
TI  - Use and effects of cannabinoids in military veterans with posttraumatic stress
      disorder.
AB  - PURPOSE: Published evidence regarding the use of cannabis and cannabis
      derivatives by military veterans with posttraumatic stress disorder (PTSD) is
      reviewed. SUMMARY: When inhaled or delivered orally or transdermally,
      cannabinoids (the psychoactive components of unrefined marijuana and various
      derivative products) activate endogenous cannabinoid receptors, modulating
      neurotransmitter release and producing a wide range of central nervous system
      effects, including increased pleasure and alteration of memory processes. Those
      effects provide a pharmacologic rationale for the use of cannabinoids to manage
      the three core PTSD symptom clusters: reexperiencing, avoidance and numbing, and
      hyperarousal. A literature search identified 11 articles pertaining to cannabis
      use by military veterans who met standard diagnostic criteria for PTSD. Cross
      sectional studies have found a direct correlation between more severe PTSD
      symptomatology and increased motivation to use cannabis for coping purposes,
      especially among patients with difficulties in emotional regulation or stress
      tolerance. Data from 4 small studies suggested that cannabinoid use was
      associated with global improvements in PTSD symptoms or amelioration of specific
      PTSD symptoms such as insomnia and nightmares. Large well-designed controlled
      trials are needed in order to better delineate the potential role of cannabinoids
      as an adjunct or alternative to conventional approaches to PTSD management.
      CONCLUSION: While further research into cannabinoid treatment effects on PTSD
      symptoms is required, the evaluated evidence indicates that substantial numbers
      of military veterans with PTSD use cannabis or derivative products to control
      PTSD symptoms, with some patients reporting benefits in terms of reduced anxiety
      and insomnia and improved coping ability.

PMID- 26195654
TI  - Laboratory replication of filtration procedures associated with Serratia
      marcescens bloodstream infections in patients receiving compounded amino acid
      solutions.
AB  - PURPOSE: Specific deviations from United States Pharmacopeia standards were
      analyzed to investigate the factors allowing an outbreak of Serratia marcescens
      bloodstream infections in patients receiving compounded amino acid solutions.
      METHODS: Filter challenge experiments using the outbreak strain of S. marcescens
      were compared with those that used the filter challenge organism recommended by
      ASTM International (Brevundimonas diminuta ATCC 19162) to determine the frequency
      and degree of organism breakthrough. Disk and capsule filters (0.22- and 0.2-MUm
      nominal pore size, respectively) were challenged with either the outbreak strain
      of S. marcescens or B. diminuta ATCC 19162. The following variables were
      compared: culture conditions in which organisms were grown overnight or cultured
      in sterile water (starved), solution type (15% amino acid solution or sterile
      water), and filtration with or without a 0.5-MUm prefilter. RESULTS: Small-scale,
      syringe-driven, disk-filtration experiments of starved bacterial cultures
      indicated that approximately 1 in every 1,000 starved S. marcescens cells (0.12%)
      was able to pass through a 0.22-MUm nominal pore-size filter, and about 1 in
      every 1,000,000 cells was able to pass through a 0.1-MUm nominal pore-size
      filter. No passage of the B. diminuta ATCC 19162 cells was observed with either
      filter. In full-scale experiments, breakthrough was observed only when 0.2-MUm
      capsule filters were challenged with starved S. marcescens in 15% amino acid
      solution without a 0.5-MUm prefiltration step. CONCLUSION: Laboratory simulation
      testing revealed that under certain conditions, bacteria can pass through 0.22-
      and 0.2-MUm filters intended for sterilization of an amino acid solution.
      Bacteria did not pass through 0.2-MUm filters when a 0.5-MUm prefilter was used.

PMID- 26195655
TI  - Stability of chlorothiazide sodium in polypropylene syringes.
AB  - PURPOSE: The stability of a solution of chlorothiazide injection diluted with
      sterile water and stored in polypropylene syringes under refrigerated conditions
      was investigated. METHODS: Chlorothiazide solutions were compounded by adding 20
      mL of sterile water for injection to a 500-mg vial of chlorothiazide sodium for
      injection. Six batches of chlorothiazide solution (25 mg/mL) were compounded; 0.5
      mL portions were transferred to 1-mL polypropylene syringes, which were sealed
      with a Luer tip cap and stored at refrigeration temperatures (2-8  degrees C)
      protected from light. Three batches were potency tested by stability-indicating
      high-performance liquid chromatography (HPLC) assay using a 0.5-mL sample from
      each batch at designated time points. Visual and pH testing were performed using
      the three remaining batches; the contents of two syringes per batch were combined
      and visually inspected for container integrity and solution color and clarity,
      with duplicate pH testing performed at each time point. RESULTS: HPLC analyses
      showed that the remaining percentage of the initial chlorothiazide content
      declined at an average daily rate of 1.4%, decreasing to 93% by day 6. All
      samples remained intact, clear, and colorless, with no visible particulate matter
      or precipitation observed throughout the study period. For all samples of
      chlorothiazide solution, pH values remained within the range of 9.2-10.0
      throughout the 10-day study period. CONCLUSION: When packaged in 1-mL
      polypropylene syringes and stored protected from light at refrigerated
      conditions, a solution of chlorothiazide sodium injection in water was stable for
      six days.

PMID- 26195656
TI  - Evaluation of pharmacy generalists performing antimicrobial stewardship services.
AB  - PURPOSE: Improvements in medication use achieved by pharmacy generalists using a
      care bundle approach to antimicrobial stewardship are reported. METHODS: A six
      month prospective, repeated-treatment, quasi-experimental study involving three
      month-long intervention periods and three month-long control periods was
      conducted in the setting of an existing antimicrobial stewardship program at a
      large hospital. The intervention involved prospective audit and feedback
      conducted by pharmacy generalists who were trained in an antimicrobial
      stewardship care bundle approach. During control months, a pharmacy generalist
      who was not trained in antimicrobial stewardship rounded with the
      multidisciplinary team and provided standard-of-care pharmacy services. The
      primary endpoint was compliance with a care bundle of four antimicrobial
      stewardship metrics: documentation of indication for therapy in the medical
      record, selection of empirical therapy according to institutional guidelines,
      documented performance of indicated culture testing, and deescalation of therapy
      when indicated. RESULTS: Two-hundred eighty-six patients were enrolled in the
      study: 124 in the intervention group and 162 in the control group. The cumulative
      rate of full compliance with all care bundle components during the six-month
      study was significantly greater during intervention months than during control
      months (68.5% versus 45.7%, p < 0.001). After adjusting for infection type,
      antimicrobial stewardship provided by an intervention-group pharmacist was
      associated with improved care bundle compliance (adjusted odds ratio, 2.70; p <
      0.001). No significant differences in patient outcomes during intervention and
      control months were detected. CONCLUSION: Pharmacy generalists trained to comply
      with a systematic care bundle approach enhanced the quality of antimicrobial
      management.

PMID- 26195657
TI  - Results of a survey to assess residency preceptor development methods and
      precepting challenges.
AB  - PURPOSE: The results of a survey to (1) assess the current status of preceptor
      development within pharmacy residency programs, (2) understand challenges to
      preceptor development, and (3) identify directions for future preceptor
      development opportunities are presented. METHODS: In June 2012, pharmacy
      residents and preceptors listed in the ASHP online residency directory were
      surveyed. The survey was developed from a review of the literature and underwent
      expert review. The final instrument included 19 preceptor-specific items and 12
      resident-specific items. RESULTS: A total of 1437 preceptors and residents
      participated in the survey. Forty-nine percent of preceptor respondents reported
      having attended a formal Residency Learning System workshop. Most surveyed
      preceptors (88.1%) felt they were adequately trained as a preceptor to be
      effective in educating pharmacy residents, but only 51.5% of preceptors felt they
      had adequate time for precepting residents. Preceptors reported the lack of time
      as the primary barrier to their development as preceptors, with 60% indicating
      that "effectively precepting while meeting employment responsibilities" was their
      primary precepting challenge. CONCLUSION: Less than half of respondents to the
      preceptor survey reported that their institutions had a policy outlining specific
      requirements for preceptor development. Preceptor survey respondents reported the
      lack of time as the primary barrier to preceptor development. Many surveyed
      residents indicated that providing effective verbal feedback and providing
      effective written feedback were the greatest challenges for their preceptors.

PMID- 26195658
TI  - Postintensive care syndrome and the role of a follow-up clinic.

PMID- 26195659
TI  - Leading clinical pharmacogenomics implementation: Advancing pharmacy practice.

PMID- 26195660
TI  - Statistics in Public Understanding of Science review: How to achieve high
      statistical standards?
AB  - This article proposes a checklist to improve statistical reporting in the
      manuscripts submitted to Public Understanding of Science. Generally, these
      guidelines will allow the reviewers (and readers) to judge whether the evidence
      provided in the manuscript is relevant. The article ends with other suggestions
      for a better statistical quality of the journal. 

PMID- 26195661
TI  - Feng Shao: Getting a sense for the defense.

PMID- 26195662
TI  - A spotlight on chromatin choreography.

PMID- 26195663
TI  - Beginning at the end: DNA replication within the telomere.
AB  - Using single molecule analysis of replicated DNA (SMARD), Drosopoulos et al.
      (2015; J. Cell Biol. http://dx.doi.org/10.1083/jcb.201410061) report that DNA
      replication initiates at measurable frequency within the telomere of mouse
      chromosome arm 14q. They demonstrate that resolution of G4 structures on the G
      rich template strand of the telomere requires some overlapping functions of BLM
      and WRN helicase for leading strand synthesis. 

PMID- 26195664
TI  - BLM helicase facilitates telomere replication during leading strand synthesis of
      telomeres.
AB  - Based on its in vitro unwinding activity on G-quadruplex (G4) DNA, the Bloom
      syndrome-associated helicase BLM is proposed to participate in telomere
      replication by aiding fork progression through G-rich telomeric DNA. Single
      molecule analysis of replicated DNA (SMARD) was used to determine the
      contribution of BLM helicase to telomere replication. In BLM-deficient cells,
      replication forks initiating from origins within the telomere, which copy the G
      rich strand by leading strand synthesis, moved slower through the telomere
      compared with the adjacent subtelomere. Fork progression through the telomere was
      further slowed in the presence of a G4 stabilizer. Using a G4-specific antibody,
      we found that deficiency of BLM, or another G4-unwinding helicase, the Werner
      syndrome-associated helicase WRN, resulted in increased G4 structures in cells.
      Importantly, deficiency of either helicase led to greater increases in G4 DNA
      detected in the telomere compared with G4 seen genome-wide. Collectively, our
      findings are consistent with BLM helicase facilitating telomere replication by
      resolving G4 structures formed during copying of the G-rich strand by leading
      strand synthesis. 

PMID- 26195665
TI  - The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle
      assembly in mammalian cells.
AB  - Deubiquitinating enzymes (DUBs) negatively regulate protein ubiquitination and
      play an important role in diverse physiological processes, including mitotic
      division. The BRCC36 isopeptidase complex (BRISC) is a DUB that is specific for
      lysine 63-linked ubiquitin hydrolysis; however, its biological function remains
      largely undefined. Here, we identify a critical role for BRISC in the control of
      mitotic spindle assembly in cultured mammalian cells. BRISC is a microtubule (MT)
      associated protein complex that predominantly localizes to the minus ends of K
      fibers and spindle poles and directly binds to MTs; importantly, BRISC promotes
      the assembly of functional bipolar spindle by deubiquitinating the essential
      spindle assembly factor nuclear mitotic apparatus (NuMA). The deubiquitination of
      NuMA regulates its interaction with dynein and importin-beta, which are required
      for its function in spindle assembly. Collectively, these results uncover BRISC
      as an important regulator of the mitotic spindle assembly and cell division, and
      have important implications for the development of anticancer drugs targeting
      BRISC. 

PMID- 26195666
TI  - IQGAP1 promotes CXCR4 chemokine receptor function and trafficking via EEA-1+
      endosomes.
AB  - IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a cytoskeleton
      interacting scaffold protein. CXCR4 is a chemokine receptor that binds stromal
      cell-derived factor-1 (SDF-1; also known as CXCL12). Both IQGAP1 and CXCR4 are
      overexpressed in cancer cell types, yet it was unclear whether these molecules
      functionally interact. Here, we show that depleting IQGAP1 in Jurkat T leukemic
      cells reduced CXCR4 expression, disrupted trafficking of endocytosed CXCR4 via
      EEA-1(+) endosomes, and decreased efficiency of CXCR4 recycling. SDF-1-induced
      cell migration and activation of extracellular signal-regulated kinases 1 and 2
      (ERK) MAPK were strongly inhibited, even when forced overexpression restored
      CXCR4 levels. Similar results were seen in KMBC and HEK293 cells. Exploring the
      mechanism, we found that SDF-1 treatment induced IQGAP1 binding to alpha-tubulin
      and localization to CXCR4-containing endosomes and that CXCR4-containing EEA-1(+)
      endosomes were abnormally located distal from the microtubule (MT)-organizing
      center (MTOC) in IQGAP1-deficient cells. Thus, IQGAP1 critically mediates CXCR4
      cell surface expression and signaling, evidently by regulating EEA-1(+) endosome
      interactions with MTs during CXCR4 trafficking and recycling. IQGAP1 may
      similarly promote CXCR4 functions in other cancer cell types. 

PMID- 26195667
TI  - Ypt1/Rab1 regulates Hrr25/CK1delta kinase activity in ER-Golgi traffic and
      macroautophagy.
AB  - ER-derived COPII-coated vesicles are conventionally targeted to the Golgi.
      However, during cell stress these vesicles also become a membrane source for
      autophagosomes, distinct organelles that target cellular components for
      degradation. How the itinerary of COPII vesicles is coordinated on these pathways
      remains unknown. Phosphorylation of the COPII coat by casein kinase 1 (CK1),
      Hrr25, contributes to the directional delivery of ER-derived vesicles to the
      Golgi. CK1 family members are thought to be constitutively active kinases that
      are regulated through their subcellular localization. Instead, we show here that
      the Rab GTPase Ypt1/Rab1 binds and activates Hrr25/CK1delta to spatially regulate
      its kinase activity. Consistent with a role for COPII vesicles and Hrr25 in
      membrane traffic and autophagosome biogenesis, hrr25 mutants were defective in ER
      Golgi traffic and macroautophagy. These studies are likely to serve as a paradigm
      for how CK1 kinases act in membrane traffic. 

PMID- 26195668
TI  - Analysis of the interplay of protein biogenesis factors at the ribosome exit site
      reveals new role for NAC.
AB  - The ribosome exit site is a focal point for the interaction of protein-biogenesis
      factors that guide the fate of nascent polypeptides. These factors include
      chaperones such as NAC, N-terminal-modifying enzymes like Methionine
      aminopeptidase (MetAP), and the signal recognition particle (SRP), which targets
      secretory and membrane proteins to the ER. These factors potentially compete with
      one another in the short time-window when the nascent chain first emerges at the
      exit site, suggesting a need for regulation. Here, we show that MetAP contacts
      the ribosome at the universal adaptor site where it is adjacent to the alpha
      subunit of NAC. SRP is also known to contact the ribosome at this site. In the
      absence of NAC, MetAP and SRP antagonize each other, indicating a novel role for
      NAC in regulating the access of MetAP and SRP to the ribosome. NAC also functions
      in SRP-dependent targeting and helps to protect substrates from aggregation
      before translocation. 

PMID- 26195669
TI  - The formation of ordered nanoclusters controls cadherin anchoring to actin and
      cell-cell contact fluidity.
AB  - Oligomerization of cadherins could provide the stability to ensure tissue
      cohesion. Cadherins mediate cell-cell adhesion by forming trans-interactions.
      They form cis-interactions whose role could be essential to stabilize
      intercellular junctions by shifting cadherin clusters from a fluid to an ordered
      phase. However, no evidence has been provided so far for cadherin oligomerization
      in cellulo and for its impact on cell-cell contact stability. Visualizing single
      cadherins within cell membrane at a nanometric resolution, we show that E
      cadherins arrange in ordered clusters, providing the first demonstration of the
      existence of oligomeric cadherins at cell-cell contacts. Studying the
      consequences of the disruption of the cis-interface, we show that it is not
      essential for adherens junction formation. Its disruption, however, increased the
      mobility of junctional E-cadherin. This destabilization strongly affected E
      cadherin anchoring to actin and cell-cell rearrangement during collective cell
      migration, indicating that the formation of oligomeric clusters controls the
      anchoring of cadherin to actin and cell-cell contact fluidity. 

PMID- 26195671
TI  - Structuration Theory: A Conceptual Framework for HIV/AIDS Stigma.
AB  - The continuing paucity of effective interventions to reduce HIV/AIDS stigma is
      troubling, given that stigma has long been recognized as a significant barrier to
      HIV prevention, treatment, care, and support. Ineffectual HIV/AIDS stigma
      reduction interventions are the product of inadequate conceptual frameworks and
      methodological tools. And while there is a paucity of effective interventions to
      reduce stigma, there is no shortage of conceptual frameworks intending to offer a
      comprehensive understanding of stigma, ranging from sociocognitive models at the
      individual level to structural models at the macrolevel. Observations
      highlighting inadequacies in the individualistic and structural models are
      offered, followed by the theory of structuration as a possible complementary
      conceptual base for designing HIV/AIDS stigma-reduction interventions. 

PMID- 26195670
TI  - Myosin 1b functions as an effector of EphB signaling to control cell repulsion.
AB  - Eph receptors and their membrane-tethered ligands, the ephrins, have important
      functions in embryo morphogenesis and in adult tissue homeostasis. Eph/ephrin
      signaling is essential for cell segregation and cell repulsion. This process is
      accompanied by morphological changes and actin remodeling that drives cell
      segregation and tissue patterning. The actin cortex must be mechanically coupled
      to the plasma membrane to orchestrate the cell morphology changes. Here, we
      demonstrate that myosin 1b that can mechanically link the membrane to the actin
      cytoskeleton interacts with EphB2 receptors via its tail and is tyrosine
      phosphorylated on its tail in an EphB2-dependent manner. Myosin 1b regulates the
      redistribution of myosin II in actomyosin fibers and the formation of filopodia
      at the interface of ephrinB1 and EphB2 cells, which are two processes mediated by
      EphB2 signaling that contribute to cell repulsion. Together, our results provide
      the first evidence that a myosin 1 functions as an effector of EphB2/ephrinB
      signaling, controls cell morphology, and thereby cell repulsion. 

PMID- 26195672
TI  - Perspectives in Primary Care: The Foundational Urgent Importance of a Shared
      Primary Care Data Model.

PMID- 26195673
TI  - Corrections.

PMID- 26195675
TI  - Salary and Quality Compensation for Physician Practices Participating in
      Accountable Care Organizations.
AB  - BACKGROUND: The accountable care organization (ACO) is a new organizational form
      to manage patients across the continuum of care. There are numerous questions
      about how ACOs should be optimally structured, including compensation
      arrangements with primary care physicians. METHODS: Using data from a national
      survey of physician practices, we compared primary care physicians' compensation
      between practices in ACOs and practices that varied in their financial risk for
      primary care costs using 3 groups: practices not participating in a Medicare ACO
      and with no substantial risk for primary care costs; practices not participating
      in an ACO but with substantial risk for primary care costs; and practices
      participating in an ACO regardless of their risk for primary care costs. We
      measured physicians' compensation as the percentage of compensation based on
      salary, productivity, clinical quality or patient experience, and other factors.
      Regression models estimated physician compensation as a function of ACO
      participation and risk for primary care costs while controlling for other
      practice characteristics. RESULTS: Physicians in ACO and non-ACO practices with
      no substantial risk for costs on average received nearly one-half of their
      compensation from salary, slightly less from productivity, and about 5% from
      quality and other factors. Physicians not in ACOs but with substantial risk for
      primary care costs received two-thirds of their compensation from salary, nearly
      one-third from productivity, and slightly more than 1% from quality and other
      factors. Participation in ACOs was associated with significantly higher physician
      compensation for quality; however, participation was not significantly associated
      with compensation from salary, whereas financial risk was associated with much
      greater compensation from salary. CONCLUSION: Although practices in ACOs provide
      higher compensation for quality, compared with practices at large, they provide a
      similar mix of compensation based on productivity and salary. Incentives for ACOs
      may not be sufficiently strong to encourage practices to change physician
      compensation policies for better patient experience, improved population health,
      and lower per capita costs.

PMID- 26195674
TI  - Community Health Center Use After Oregon's Randomized Medicaid Experiment.
AB  - PURPOSE: There is debate about whether community health centers (CHCs) will
      experience increased demand from patients gaining coverage through Affordable
      Care Act Medicaid expansions. To better understand the effect of new Medicaid
      coverage on CHC use over time, we studied Oregon's 2008 randomized Medicaid
      expansion (the "Oregon Experiment"). METHODS: We probabilistically matched
      demographic data from adults (aged 19-64 years) participating in the Oregon
      Experiment to electronic health record data from 108 Oregon CHCs within the OCHIN
      community health information network (originally the Oregon Community Health
      Information Network) (N = 34,849). We performed intent-to-treat analyses using
      zero-inflated Poisson regression models to compare 36-month (2008-2011) usage
      rates among those selected to apply for Medicaid vs not selected, and
      instrumental variable analyses to estimate the effect of gaining Medicaid
      coverage on use. Use outcomes included primary care visits, behavioral/mental
      health visits, laboratory tests, referrals, immunizations, and imaging. RESULTS:
      The intent-to-treat analyses revealed statistically significant differences in
      rates of behavioral/mental health visits, referrals, and imaging between patients
      randomly selected to apply for Medicaid vs those not selected. In instrumental
      variable analyses, gaining Medicaid coverage significantly increased the rate of
      primary care visits, laboratory tests, referrals, and imaging; rate ratios ranged
      from 1.27 (95% CI, 1.05-1.55) for laboratory tests to 1.58 (95% CI, 1.10-2.28)
      for referrals. CONCLUSIONS: Our results suggest that use of many different types
      of CHC services will increase as patients gain Medicaid through Affordable Care
      Act expansions. To maximize access to critical health services, it will be
      important to ensure that the health care system can support increasing demands by
      providing more resources to CHCs and other primary care settings.

PMID- 26195676
TI  - Sleep Apnea and Risk of Panic Disorder.
AB  - PURPOSE: Epidemiological studies have identified a trend in the development of
      depressive and anxiety disorders following a diagnosis of sleep apnea. The
      relationship between sleep apnea and subsequent panic disorder, however, remains
      unclear. METHODS: Using a nationwide database, the Taiwan National Health
      Insurance Research Database, patients with sleep apnea and age-, sex-, income-,
      and urbanization-matched control patients who did not have sleep apnea were
      enrolled between 2000 and 2010. Patients with a prior diagnosis of panic disorder
      before enrollment were excluded. The 2 cohorts were observed until December 31,
      2010. The primary endpoint was occurrence of newly diagnosed panic disorder.
      RESULTS: A total of 8,704 sleep apnea patients and 34,792 control patients were
      enrolled. Of the 43,496 patients, 263 (0.60%) suffered from panic disorder during
      a mean follow-up period of 3.92 years, including 117 (1.34%) from the sleep apnea
      cohort and 146 (0.42%) from the control group. The Kaplan-Meier analysis revealed
      a predisposition of patients with sleep apnea to develop panic disorder (log-rank
      test, P <.001). After multivariate adjustment, the hazard ratio for subsequent
      panic disorder among the sleep apnea patients was 2.17 (95% confidence interval,
      1.68-2.81; P <.001). CONCLUSIONS: Sleep apnea appears to confer a higher risk for
      future development of panic disorder.

PMID- 26195677
TI  - Erectile Dysfunction and Undiagnosed Diabetes, Hypertension, and
      Hypercholesterolemia.
AB  - PURPOSE: We investigated whether erectile dysfunction, a marker for future
      cardiovascular disease, is associated with undiagnosed cardiometabolic risk
      factors among US men. Identifying the presence of these risk factors could lead
      to earlier initiation of treatment for primary prevention of cardiovascular
      disease. METHODS: We analyzed cross-sectional data from men aged 20 years and
      older who participated in the National Health and Nutrition Examination Survey
      during 2001-2004. Erectile dysfunction was determined by a single, validated
      survey question. We used logistic regression analyses to investigate the
      relationship between erectile dysfunction and undiagnosed hypertension,
      hypercholesterolemia, and diabetes. RESULTS: After multivariate adjustment, men
      with erectile dysfunction had more than double the odds of having undiagnosed
      diabetes (odds ratio = 2.20; 95% CI, 1.10-4.37), whereas no association was seen
      for undiagnosed hypertension or undiagnosed hypercholesterolemia. For the average
      man aged 40 to 59 years, the predicted probability of having undiagnosed diabetes
      increased from 1 in 50 in the absence of erectile dysfunction to 1 in 10 in the
      presence of erectile dysfunction. CONCLUSIONS: Our results underscore the
      importance of erectile dysfunction as a marker of undiagnosed diabetes. Erectile
      dysfunction should be a trigger to initiate diabetes screening, particularly
      among middle-aged men.

PMID- 26195678
TI  - Correlates of Sexual Activity and Satisfaction in Midlife and Older Women.
AB  - PURPOSE: Sexual activity is an important component of quality of life for women
      across their lifespan. Prior studies show a decline in sexual activity with age,
      but these studies often fail to consider the role of sexual satisfaction. The aim
      of this study is to give updated prevalence estimates of sexual activity among
      women and to elucidate factors associated with sexual activity and sexual
      satisfaction. METHODS: We report a cross-sectional analysis of the second wave of
      a nationally representative sample of US adults aged 28 to 84 years, the Survey
      of Midlife Development in the United States. The survey used self-administered
      questionnaires to assess demographic data, self-rated physical and mental health,
      medical problems and medication use, relationship factors, and sexual activity
      and satisfaction. RESULTS: Of 2,116 women who answered the questions regarding
      sexuality, 1,345 (61.8%) women were sexually active in the previous 6 months. The
      proportion of women who were sexually active decreased with advancing age. Women
      who were married or cohabitating had approximately 8 times higher odds of being
      sexually active (odds ratio = 7.91, 95% CI, 4.16-15.04; P <.001). Among women
      aged 60 years and older who were married or cohabitating, most (59.0%) were
      sexually active. Among women who were sexually active, higher relationship
      satisfaction (P <.001), better communication (P = .011), and higher importance of
      sex P = .040) were related to higher sexual satisfaction, but age was not (P =
      .79). CONCLUSIONS: A considerable proportion of midlife and older women remain
      sexually active if they have a partner available. Psychosocial factors
      (relationship satisfaction, communication with romantic partner, and importance
      of sex) matter more to sexual satisfaction than aging among midlife and older
      women.

PMID- 26195679
TI  - Rates of Anomalous Bupropion Prescriptions in Ontario, Canada.
AB  - PURPOSE: Reports of bupropion misuse have increased since it was first reported
      in 2002. The purpose of this study was to explore trends in bupropion prescribing
      suggestive of misuse or diversion in Ontario, Canada. METHODS: A serial cross
      sectional study was conducted of Ontarians aged younger than 65 years who
      received prescriptions under Ontario's public drug program from April 1, 2000, to
      March 31, 2013. We determined the number of potentially inappropriate
      prescriptions in each quarter, defined as early refills dispensed within 50% of
      the duration of the preceding prescription, as well as potentially duplicitous
      prescriptions, defined as similarly early refills originating from a different
      prescriber and different pharmacy. We replicated these analyses for citalopram
      and sertraline, antidepressants not known to be prone to abuse. RESULTS: We
      identified 1,780,802 prescriptions for bupropion, 3,402,462 for citalopram, and
      1,775,285 for sertraline. Rates of early refills for bupropion declined during
      the study from 4.8% to 3.1%. In the final quarter, rates of early refills for
      bupropion were more common than for citalopram (3.1% vs 2.2%) (P <.001) but not
      for sertraline (3.1% vs 2.9%) (P =.16). Potentially duplicitous prescriptions for
      bupropion increased dramatically, from <0.05% of all prescriptions in early 2000
      to 0.47% in early 2013 and by the final quarter were more common than both
      citalopram (0.11%) and sertraline (0.12%) (P <.001). CONCLUSIONS: Although no
      marked differences were seen for early refills of bupropion relative to its
      comparators, potentially duplicitous prescriptions have increased dramatically in
      Ontario, suggesting growing misuse of the drug.

PMID- 26195680
TI  - Exploring the Patient and Staff Experience With the Process of Primary Care.
AB  - PURPOSE: Previous studies suggest that the highest-risk patients value
      accessible, coordinated primary care that they perceive to be of high technical
      quality. We have limited understanding, however, of how low-income, chronically
      ill patients and the staff who care for them experience each individual step in
      the primary care process. METHODS: We conducted qualitative interviews with
      uninsured or Medicaid patients with chronic illnesses, as well as with primary
      care staff. We interviewed 21 patients and 30 staff members with a variety of job
      titles from 3 primary care practices (1 federally qualified health center and 2
      academically affiliated clinics).] RESULTS: The interviews revealed 3 major
      issues that were present at all stages of a primary care episode: (1) information
      flow throughout an episode of care is a frequent challenge, despite systems that
      are intended to improve communication; (2) misaligned goals and expectations
      among patients, clinicians, and staff members are often an impediment to
      providing and obtaining care; and (3) personal relationships are highly valued by
      both patients and staff. CONCLUSIONS: Vulnerable populations and the primary care
      staff who work with them perceive some of the same challenges throughout the
      primary care process. Improving information flow, aligning goals and
      expectations, and developing personal relationships may improve the experience of
      both patients and staff.

PMID- 26195681
TI  - Catching Up With the HPV Vaccine: Challenges and Opportunities in Primary Care.
AB  - PURPOSE: Data confirm that high rates of human papillomavirus (HPV) vaccination
      have not been achieved despite strong clinician endorsement of the vaccine. We
      conducted a study of primary care clinicians to assess the broad range of health
      care delivery, health policy, and attitudinal factors influencing vaccination
      uptake and opportunities for informed decision making. METHODS: We implemented a
      mixed methods study in RIOS Net, a primary care practice-based research network
      in New Mexico. We first conducted qualitative, in-depth interviews with primary
      care clinicians, health policy makers, and immunization experts, and followed up
      with a confirmatory survey distributed to RIOS Net clinician members. RESULTS:
      Health service delivery challenges emerged as the greatest barrier to HPV
      vaccination, specifically the lack of capacity to track and distribute reminders
      to eligible patients. Clinicians also reported variations in counseling
      approaches attributable to both age and emphasis on the cancer prevention
      benefits of the vaccine. There was no evidence of sociocultural influences on
      vaccine decision making, nor did concerns about perceived overprotection emerge.
      CONCLUSIONS: Our findings, based on a long-term program of research, suggest that
      both patients' attributes and health system delivery are most influential in HPV
      vaccination coverage challenges. Interventions targeting innovative communication
      techniques, as well as health system changes that build on efforts toward
      coordinated care and utilization of other venues to promote vaccination, will be
      necessary to address these challenges.

PMID- 26195682
TI  - Impact of Cervical Cancer Screening Guidelines on Screening for Chlamydia.
AB  - The highest prevalence of chlamydia infection in the United States is among
      people aged 15 to 24 years. We assessed the impact of not doing routine cervical
      cancer screening on the rates of chlamydia screening in women aged 15 to 21
      years. We classified visits to family medicine ambulatory clinics according to
      their timing relative to the 2009 guideline change that led to more restrictive
      cervical cancer screening. Women had higher odds of being screened for chlamydia
      before vs after the guideline change (odds ratio = 13.97; 95% CI, 9.17-21.29; P
      <.001). Chlamydia and cervical cancer screening need to be uncoupled and new
      screening opportunities should be identified. 

PMID- 26195683
TI  - Development and Validation of Search Filters to Identify Articles on Family
      Medicine in Online Medical Databases.
AB  - Physicians and researchers in the field of family medicine often need to find
      relevant articles in online medical databases for a variety of reasons. Because a
      search filter may help improve the efficiency and quality of such searches, we
      aimed to develop and validate search filters to identify research studies of
      relevance to family medicine. Using a new and objective method for search filter
      development, we developed and validated 2 search filters for family medicine. The
      sensitive filter had a sensitivity of 96.8% and a specificity of 74.9%. The
      specific filter had a specificity of 97.4% and a sensitivity of 90.3%. Our new
      filters should aid literature searches in the family medicine field. The
      sensitive filter may help researchers conducting systematic reviews, whereas the
      specific filter may help family physicians find answers to clinical questions at
      the point of care when time is limited. 

PMID- 26195684
TI  - Accountable Communities for Health: Moving From Providing Accountable Care to
      Creating Health.
AB  - Lessons from community-oriented primary care in the United States can offer
      insights into how we could improve population health by integrating the public
      health, social service, and health care sectors to form accountable communities
      for health (ACHs). Unlike traditional accountable care organizations (ACOs) that
      address population health from a health care perspective, ACHs address health
      from a community perspective and consider the total investment in health across
      all sectors. The approach embeds the ACO in a community context where multiple
      stakeholders come together to share responsibility for tackling multiple
      determinants of health. ACOs using the ACH model provide a roadmap for embedding
      health care in communities in a way that uniquely addresses local social
      determinants of health. 

PMID- 26195685
TI  - Affordable Care?
AB  - Once a year, Stuart, a long-haul truck driver, visited a physician to get a
      signature on the forms that allowed him to continue driving his 18-wheeler. Over
      8 years, he had never seen the same physician twice, in large part because of a
      lack of health insurance. Upon seeing him for the first time, I assured him that
      we could make financial arrangements, and he subsequently became my continuity
      patient. Two years later, we both looked forward to his impending 65th birthday,
      allowing Medicare to ease his fiscal health care burdens. His unexpected death
      made me ponder how a lack of access to affordable health care profoundly affects
      patients and their clinicians. 

PMID- 26195687
TI  - Openings.
AB  - Reviewing his clinic patient schedule for the day, a physician reflects on the
      history of a young woman he has been caring for over the past 9 years. What
      starts out as a routine visit then turns into a unique opening for communication
      and connection. A chance glimpse out the window of the exam room leads to a
      deeper meditation on parenthood, survival, and healing, not only for the patient
      but also for the physician. How many missed opportunities have we all had,
      without even realizing it, to allow this kind of fleeting but profound opening? 

PMID- 26195686
TI  - Making Personalized Health Care Even More Personalized: Insights From Activities
      of the IOM Genomics Roundtable.
AB  - Genomic research has generated much new knowledge into mechanisms of human
      disease, with the potential to catalyze novel drug discovery and development,
      prenatal and neonatal screening, clinical pharmacogenomics, more sensitive risk
      prediction, and enhanced diagnostics. Genomic medicine, however, has been limited
      by critical evidence gaps, especially those related to clinical utility and
      applicability to diverse populations. Genomic medicine may have the greatest
      impact on health care if it is integrated into primary care, where most health
      care is received and where evidence supports the value of personalized medicine
      grounded in continuous healing relationships. Redesigned primary care is the most
      relevant setting for clinically useful genomic medicine research. Taking insights
      gained from the activities of the Institute of Medicine (IOM) Roundtable on
      Translating Genomic-Based Research for Health, we apply lessons learned from the
      patient-centered medical home national experience to implement genomic medicine
      in a patient-centered, learning health care system. 

PMID- 26195688
TI  - RESIDENCY PROGRAMS GEAR UP FOR NEW RESIDENCY CLASS WITH STFM RESOURCES.

PMID- 26195689
TI  - ADVANCING THE PRIMARY/SPECIALTY CARE INTERFACE THROUGH ECONSULTS AND ENHANCED
      REFERRALS.

PMID- 26195690
TI  - PROGRAM DIRECTORS AND CERA: AN IMPORTANT RELATIONSHIP.

PMID- 26195691
TI  - EXPANDING NAPCRG'S LEADERSHIP CAPACITY.

PMID- 26195692
TI  - FAMILY PHYSICIAN SALARIES UP, BUT STILL TRAIL THOSE OF SUBSPECIALISTS.

PMID- 26195693
TI  - THE AMERICAN BOARD OF FAMILY MEDICINE FOUNDATION INAUGURATES THE G. GAYLE
      STEPHENS KEYSTONE CONFERENCE SERIES.

PMID- 26195695
TI  - Second-Line Therapy for Endometrial Cancer: The Need for Better Options.

PMID- 26195696
TI  - Impact of Age and Primary Disease Site on Outcome in Women With Low-Grade Serous
      Carcinoma of the Ovary or Peritoneum: Results of a Large Single-Institution
      Registry of a Rare Tumor.
AB  - PURPOSE: Low-grade serous carcinoma of the ovary (LGSOC) or peritoneum (LGSPC) is
      a rare subtype of ovarian or peritoneal cancer characterized by young age at
      diagnosis and relative resistance to chemotherapy. The purpose of this study is
      to report our updated experience with women diagnosed with LGSOC or LGSPC to
      assess the validity of our original observations. PATIENTS AND METHODS:
      Eligibility criteria for patients from our database were: stage I to IV LGSOC or
      LGSPC, original diagnosis before January 2012, and adequate clinical information.
      All patients were included in progression-free survival, overall survival, and
      multivariable Cox regression analyses. A subset analysis was performed among
      patients with stage II to IV low-grade serous carcinoma treated with primary
      surgery followed by platinum-based chemotherapy. RESULTS: We identified 350
      eligible patients. Median progression-free survival was 28.1 months; median
      overall survival was 101.7 months. In the multivariable analysis, compared with
      women age <= 35 years, those diagnosed at age > 35 years had a 43% reduction in
      likelihood of dying (hazard ratio, 0.53; 95% CI, 0.37 to 0.74; P < .001). Having
      disease present at completion of primary therapy was associated with a 1.78
      increased hazard of dying compared with being clinically disease free (P < .001).
      Similar trends were noted in the smaller patient cohort. In this cohort, women
      with LGSPC had a 41% decreased chance of dying (hazard ratio, 0.59; 95% CI, 0.36
      to 0.98; P = .04) compared with those with LGSOC. CONCLUSION: Women age < 35
      years with low-grade serous carcinoma and those with persistent disease at
      completion of primary therapy have the worst outcomes. Patients with LGSPC seem
      to have a better prognosis than those with LGSOC.

PMID- 26195697
TI  - Improving the Evidence Base for Treating Older Adults With Cancer: American
      Society of Clinical Oncology Statement.
AB  - The American Society of Clinical Oncology (ASCO) convened a subcommittee to
      develop recommendations on improving the evidence base for treating older adults
      with cancer in response to a critical need identified by the Institute of
      Medicine. Older adults experience the majority of cancer diagnoses and deaths and
      make up the majority of cancer survivors. Older adults are also the fastest
      growing segment of the US population. However, the evidence base for treating
      this population is sparse, because older adults are underrepresented in clinical
      trials, and trials designed specifically for older adults are rare. The result is
      that clinicians have less evidence on how to treat older adults, who represent
      the majority of patients with cancer. Clinicians and patients are forced to
      extrapolate from trials conducted in younger, healthier populations when
      developing treatment plans. This has created a dearth of knowledge regarding the
      risk of toxicity in the average older patient and about key end points of
      importance to older adults. ASCO makes five recommendations to improve evidence
      generation in this population: (1) Use clinical trials to improve the evidence
      base for treating older adults with cancer, (2) leverage research designs and
      infrastructure for generating evidence on older adults with cancer, (3) increase
      US Food and Drug Administration authority to incentivize and require research
      involving older adults with cancer, (4) increase clinicians' recruitment of older
      adults with cancer to clinical trials, and (5) use journal policies to improve
      researchers' reporting on the age distribution and health risk profiles of
      research participants. 

PMID- 26195698
TI  - Postoperative Radiation Therapy: Passing the Baton for Local Control.

PMID- 26195699
TI  - Can We Predict Bevacizumab Responders in Patients With Glioblastoma?

PMID- 26195700
TI  - Reply to D. Spiegel.

PMID- 26195702
TI  - Salvage Surgery After Chemoradiotherapy in the Management of Esophageal Cancer:
      Is It a Viable Therapeutic Option?
AB  - PURPOSE: The aim of this large multicenter study was to assess the impact of
      salvage esophagectomy after definitive chemoradiotherapy (SALV) on clinical
      outcome. PATIENTS AND METHODS: Data from consecutive adult patients undergoing
      resection for esophageal cancer in 30 European centers from 2000 to 2010 were
      collected. First, groups undergoing SALV (n = 308) and neoadjuvant
      chemoradiotherapy followed by planned esophagectomy (NCRS; n = 540) were
      compared. Second, patients who benefited from SALV for persistent (n = 234)
      versus recurrent disease (n = 74) were compared. Propensity score matching and
      multivariable analyses were used to compensate for differences in some baseline
      characteristics. RESULTS: SALV versus NCRS groups: In-hospital mortality was
      similar in both groups (8.4% v 9.3%). The only significant differences in
      complications were seen for anastomotic leak (17.2% v 10.7%; P = .007) and
      surgical site infection, which were both more frequent in the SALV group. At 3
      years, groups had similar overall (43.3% v 40.1%; P = .542) and disease-free
      survival (39.2% v 32.8%; P = .232) after matching, along with a similar
      recurrence pattern. Persistent versus recurrent disease groups: There were no
      significant differences between groups in incidence of in-hospital mortality or
      major complications. At 3 years, overall (40.9% v 56.2%; P = .046) and disease
      free survival (36.6% v 51.6%; P = .095) were lower in the persistent disease
      group. CONCLUSION: The results of this large multicenter study from the modern
      era suggest that SALV can offer acceptable short- and long-term outcomes in
      selected patients at experienced centers. Persistent cancer after definitive
      chemoradiotherapy seems to be more biologically aggressive, with poorer survival
      compared with recurrent cancer.

PMID- 26195701
TI  - Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma.
AB  - Lenalidomide is an orally active immunomodulatory drug that has direct
      antineoplastic activity and indirect effects mediated through multiple types of
      immune cells found in the tumor microenvironment, including B, T, natural killer
      (NK), and dendritic cells. Recently, the E3 ubiquitin ligase cereblon was
      identified as a molecular target that may underlie the effects of lenalidomide on
      tumor cells, as well as on cells in the tumor microenvironment. Decreases in
      cereblon attenuate these effects and also confer resistance to lenalidomide.
      Tumoricidal effects of lenalidomide are associated with reduced interferon
      regulatory factor 4, a downstream target of cereblon. Lenalidomide stimulates
      proliferation and activation of NK cells, thereby enhancing NK cell-mediated
      cytotoxicity and antibody-dependent cellular cytotoxicity. These effects appear
      to be secondary to cytokine production from T cells. Lenalidomide has been shown
      to produce synergistic effects in experimental models when evaluated in
      combination with rituximab, dexamethasone, bortezomib, and B-cell receptor
      signaling inhibitors, consistent with mechanisms complementary to these agents.
      These experimental findings have translated to the clinic, where single-agent use
      displays durable responses in relapsed/refractory non-Hodgkin lymphoma, and
      combination with rituximab and other agents leads to improved responses at first
      line and in relapsed/refractory disease. The activity of lenalidomide is evident
      across multiple lymphoma subtypes, including indolent and aggressive forms. The
      interaction among cell types in the immune microenvironment is increasingly
      recognized as important to tumor cell recognition and destruction, as well as to
      protection of normal immune cells, as reflected by lenalidomide studies across
      multiple types of B-cell lymphomas. 

PMID- 26195703
TI  - Reply to K. Lu.

PMID- 26195704
TI  - Economic Benefits of Palliative Care Consultation Continue to Unfold.

PMID- 26195705
TI  - Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With
      Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice
      Guideline.
AB  - PURPOSE: To provide recommendations on the appropriate use of breast tumor
      biomarker assay results to guide decisions on systemic therapy for metastatic
      breast cancer. METHODS: A literature search and prospectively defined study
      selection identified systematic reviews, meta-analyses, randomized controlled
      trials (RCTs), prospective-retrospective studies, and prospective comparative
      observational studies published from 2006 through September 2014. RESULTS: The
      literature search revealed 17 articles that met criteria for further review: 11
      studies reporting discordances between primary tumors and metastases in
      expression of hormone receptors or human epidermal growth factor receptor 2
      (HER2), one RCT that addressed the use of a biomarker to decide whether to change
      or continue a treatment regimen, and five prospective-retrospective studies that
      evaluated the clinical utility of biomarkers. RECOMMENDATIONS: In patients with
      accessible metastases, biopsy for confirmation of disease process and retesting
      of estrogen receptor, progesterone receptor, and HER2 status should be offered,
      but evidence is lacking to determine whether changing anticancer treatment on the
      basis of change in receptor status affects clinical outcomes. With discordance of
      results between primary and metastatic tissues, the Panel consensus is to use
      preferentially the estrogen receptor, progesterone receptor, and HER2 status of
      the metastasis to direct therapy if supported by the clinical scenario and
      patient's goals for care. Carcinoembryonic antigen, cancer antigen 15-3, and
      cancer antigen 27-29 may be used as adjunctive assessments, but not alone, to
      contribute to decisions regarding therapy. Recommendations for tumor rebiopsy and
      use of circulating tumor markers are based on clinical experience and Panel
      informal consensus in the absence of studies designed to evaluate the clinical
      utility of the markers. As such, it is also reasonable for clinicians to not use
      these markers as adjunctive assessments.

PMID- 26195706
TI  - Reply to P. Baldo et al.

PMID- 26195707
TI  - Dexrazoxane in Children With Cancer: From Evidence to Practice.

PMID- 26195708
TI  - Reply to H.J. Lee et al.

PMID- 26195709
TI  - Improvements in US Breast Cancer Survival and Proportion Explained by Tumor Size
      and Estrogen-Receptor Status.
AB  - PURPOSE: Breast cancer mortality began declining in many Western countries during
      the late 1980s. We estimated the proportion of improvements in stage- and age
      specific breast cancer survival in the United States explained by tumor size or
      estrogen receptor (ER) status. METHODS: We estimated hazard ratios for breast
      cancer-specific death from time of invasive breast cancer diagnosis in the
      National Cancer Institute's Surveillance, Epidemiology, and End Results 9
      Registries Database from 1973 to 2010, with and without stratification by tumor
      size and ER status. RESULTS: Hazards from breast cancer-specific death declined
      from 1973 to 2010, not only in the first 5 years after diagnosis, but also
      thereafter. Stratification by tumor size explained less than 17% of the
      improvements comparing 2005 to 2010 versus 1973 to 1979, except for women age >=
      70 years with local (49%) or regional (38%) disease. Tumor size usually accounted
      for more of the improvement in the first 5 years after diagnosis than later.
      Additional adjustment for ER status (positive, negative, or unknown) from 1990 to
      2010 did not explain much more of the improvement, except for women age >= 70
      years within 5 years after diagnosis. CONCLUSION: Most stage-specific survival
      improvement in women younger than age 70 years old is unexplained by tumor size
      and ER status, suggesting a key role for treatment. In the first 5 years after
      diagnosis, tumor size contributed importantly for women >= 70 years old with
      local and regional stage, and stratification by tumor size and ER status
      explained even more of the survival improvement among women age >= 70 years.

PMID- 26195710
TI  - Modernizing Eligibility Criteria for Molecularly Driven Trials.
AB  - As more clinical trials of molecularly targeted agents evolve, the number of
      eligibility criteria seems to be increasing. The importance and utility of
      eligibility criteria must be considered in the context of the fundamental goal of
      a clinical trial: to understand the risks and benefits of a treatment in the
      intended-use patient population. Although eligibility criteria are necessary to
      define the population under study and conduct trials safely, excessive
      requirements may severely restrict the population available for study, and often,
      this population is not reflective of the general population for which the drug
      would be prescribed. The American Society of Clinical Oncology Cancer Research
      Committee, which comprises academic faculty, industry representatives, and
      patient advocates, evaluated this issue. Evaluation results were mixed. Most
      physicians agreed that excessive eligibility criterias slow study enrollment
      rates and prolong the duration of enrollment; however, this hypothesis was
      difficult to validate with the data examined. We propose the organization of a
      public workshop, with input from regulatory bodies and key stakeholders, with the
      goal of developing an algorithmic approach to determining eligibility criteria
      for individual study protocols, which may help guide future investigators and
      companies in streamlining eligibility criteria in the era of molecularly driven
      therapy. 

PMID- 26195711
TI  - High Prevalence of Hereditary Cancer Syndromes in Adolescents and Young Adults
      With Colorectal Cancer.
AB  - PURPOSE: Established guidelines recommend evaluation for hereditary cancer
      syndromes in patients younger than 50 years diagnosed with colorectal cancer
      (CRC). This group has been well described in the literature; however, patients
      diagnosed as adolescents and young adults are not well represented in CRC
      studies. Here, we define the clinical profile, including the extent of hereditary
      cancer syndromes and family history of cancer, in patients diagnosed with CRC at
      age 35 or younger. PATIENTS AND METHODS: We reviewed patients who underwent
      genetic counseling at our institution during 5 years (2009 to 2013). Data were
      collected regarding demographics, clinicopathologic information, tumor and
      genetic testing, and family history. Patients with an identified hereditary
      cancer syndrome were compared with those without a syndrome. RESULTS: Of the 193
      patients with evaluable data, 35% had an identifiable hereditary cancer syndrome,
      including 23 with Lynch syndrome, 22 with mutation-negative Lynch syndrome, 16
      with familial adenomatous polyposis, two with constitutional mismatch repair
      deficiency, two with biallelic MUTYH mutations, and one with Li-Fraumeni
      syndrome. Patients without a hereditary syndrome more frequently presented with
      metastatic disease, whereas patients with a syndrome were more likely to present
      at earlier stages and to have a family history of cancer. Nevertheless, a
      substantial proportion of the hereditary syndromes (19%) were diagnosed in
      individuals with no family history of the disease. CONCLUSION: We conclude that
      patients diagnosed with CRC at age 35 years or younger should receive genetic
      counseling regardless of their family history and phenotype.

PMID- 26195712
TI  - Depth of Invasion in High-Grade T1 Bladder Cancer: Added Value In Timely
      Cystectomy?

PMID- 26195713
TI  - Smoothened Inhibitors in Sonic Hedgehog Subgroup Medulloblastoma.

PMID- 26195714
TI  - Just Toxicity, or Toxicity As a Biomarker of Efficacy of Ramucirumab in Breast
      Cancer?

PMID- 26195716
TI  - Predictive Value of Positron Emission Tomography/Computed Tomography to Assess
      Early Treatment Response to Dual Human Epidermal Growth Factor Receptor 2 (HER2)
      Blockade Without Chemotherapy for HER2-Positive Metastatic Breast Cancer: Are We
      Ready to Embrace This "Early Metabolic Look" Strategy?

PMID- 26195715
TI  - Cancer Care Delivery Research: Building the Evidence Base to Support Practice
      Change in Community Oncology.
AB  - Understanding how health care system structures, processes, and available
      resources facilitate and/or hinder the delivery of quality cancer care is
      imperative, especially given the rapidly changing health care landscape. The
      emerging field of cancer care delivery research (CCDR) focuses on how
      organizational structures and processes, care delivery models, financing and
      reimbursement, health technologies, and health care provider and patient
      knowledge, attitudes, and behaviors influence cancer care quality, cost, and
      access and ultimately the health outcomes and well-being of patients and
      survivors. In this article, we describe attributes of CCDR, present examples of
      studies that illustrate those attributes, and discuss the potential impact of
      CCDR in addressing disparities in care. We conclude by emphasizing the need for
      collaborative research that links academic and community-based settings and
      serves simultaneously to accelerate the translation of CCDR results into
      practice. The National Cancer Institute recently launched its Community Oncology
      Research Program, which includes a focus on this area of research. 

PMID- 26195717
TI  - Biliary Tract Cancers: Finding Better Ways to Lump and Split.

PMID- 26195718
TI  - Toxicities and Adverse Drug Reactions Experienced During Anticancer Treatment: It
      Is Desirable to Consider the Problem Within the International System of
      Pharmacovigilance.

PMID- 26195719
TI  - Existential Psychotherapy for Patients With Advanced Cancer: Facing the Future
      and the Past.

PMID- 26195721
TI  - Tumor Genetic Screening Programs: A Call to Action.

PMID- 26195720
TI  - Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides
      and Sezary Syndrome With Variable CD30 Expression Level: A Multi-Institution
      Collaborative Project.
AB  - PURPOSE: In contrast to Hodgkin lymphoma and systemic anaplastic large-cell
      lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and
      Sezary syndrome (SS) is quite variable. Clinical activity and safety of
      brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in
      MF and SS. Tissue and blood biomarkers of clinical response were explored.
      PATIENTS AND METHODS: In this phase II study, patients with MF or SS with
      negligible to 100% CD30 expression levels were treated with brentuximab vedotin
      (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point
      was overall global response rate. Secondary end points included correlation of
      tissue CD30 expression level with clinical response, time to response, duration
      of response, progression-free and event-free survivals, and safety. RESULTS: Of
      the 32 patients enrolled and treated, 30 patients had available efficacy
      evaluations. Objective global response was observed in 21 (70%) of 30 patients
      (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly
      variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30
      expression had a lower likelihood of global response than did those with 5% or
      greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages,
      many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was
      the most common adverse event. CONCLUSION: Brentuximab vedotin demonstrated
      significant clinical activity in treatment-refractory or advanced MF or SS with a
      wide range of CD30 expression levels. Additional biomarker studies may help
      optimize rational design of combination therapies with brentuximab vedotin.

PMID- 26195722
TI  - "Right-to-Try" Legislation: Progress or Peril?

PMID- 26195724
TI  - Basigin is a druggable target for host-oriented antimalarial interventions.
AB  - Plasmodium falciparum is the parasite responsible for the most lethal form of
      malaria, an infectious disease that causes a large proportion of childhood deaths
      and poses a significant barrier to socioeconomic development in many countries.
      Although antimalarial drugs exist, the repeated emergence and spread of drug
      resistant parasites limit their useful lifespan. An alternative strategy that
      could limit the evolution of drug-resistant parasites is to target host factors
      that are essential and universally required for parasite growth. Host-targeted
      therapeutics have been successfully applied in other infectious diseases but have
      never been attempted for malaria. Here, we report the development of a
      recombinant chimeric antibody (Ab-1) against basigin, an erythrocyte receptor
      necessary for parasite invasion as a putative antimalarial therapeutic. Ab-1
      inhibited the PfRH5-basigin interaction and potently blocked erythrocyte invasion
      by all parasite strains tested. Importantly, Ab-1 rapidly cleared an established
      P. falciparum blood-stage infection with no overt toxicity in an in vivo
      infection model. Collectively, our data demonstrate that antibodies or other
      therapeutics targeting host basigin could be an effective treatment for patients
      infected with multi-drug resistant P. falciparum. 

PMID- 26195723
TI  - Novel Biomarker Signature That May Predict Aggressive Disease in African American
      Men With Prostate Cancer.
AB  - PURPOSE: We studied the ethnicity-specific expression of prostate cancer (PC) 
      associated biomarkers to evaluate whether genetic/biologic factors affect ethnic
      disparities in PC pathogenesis and disease progression. PATIENTS AND METHODS: A
      total of 154 African American (AA) and 243 European American (EA) patients from
      four medical centers were matched according to the Cancer of the Prostate Risk
      Assessment postsurgical score within each institution. The distribution of mRNA
      expression levels of 20 validated biomarkers reported to be associated with PC
      initiation and progression was compared with ethnicity using false discovery
      rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models. A
      conditional logistic regression model was used to evaluate the interaction
      between ethnicity and biomarkers for predicting clinicopathologic outcomes.
      RESULTS: Of the 20 biomarkers examined, six showed statistically significant
      differential expression in AA compared with EA men in one or more statistical
      models. These include ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1
      (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04). Dysregulation of
      AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) as well
      as loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P
      = .037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner.
      Dysregulation of GOLM1 (P = .037), SRD5A2 (P = .023), and MKi67 (P = .023)
      predicted clinical outcomes, including 3-year biochemical recurrence and
      metastasis at 5 years. A greater proportion of AA men than EA men had triple
      negative (ERG-negative/ETS-negative/SPINK1-negative) disease (51% v 35%; P =
      .002). CONCLUSION: We have identified a subset of PC biomarkers that predict the
      risk of clinicopathologic outcomes in an ethnicity-dependent manner. These
      biomarkers may explain in part the biologic contribution to ethnic disparity in
      PC outcomes between EA and AA men.

PMID- 26195725
TI  - Identification of resolvin D2 receptor mediating resolution of infections and
      organ protection.
AB  - Endogenous mechanisms that orchestrate resolution of acute inflammation are
      essential in host defense and the return to homeostasis. Resolvin (Rv)D2 is a
      potent immunoresolvent biosynthesized during active resolution that
      stereoselectively stimulates resolution of acute inflammation. Here, using an
      unbiased G protein-coupled receptor-beta-arrestin-based screening and functional
      sensing systems, we identified a receptor for RvD2, namely GPR18, that is
      expressed on human leukocytes, including polymorphonuclear neutrophils (PMN),
      monocytes, and macrophages (MPhi). In human MPhi, RvD2-stimulated intracellular
      cyclic AMP was dependent on GPR18. RvD2-stimulated phagocytosis of Escherichia
      coli and apoptotic PMN (efferocytosis) were enhanced with GPR18 overexpression
      and significantly reduced by shRNA knockdown. Specific binding of RvD2 to
      recombinant GPR18 was confirmed using a synthetic (3)H-labeled-RvD2. Scatchard
      analysis gave a Kd of ~10 nM consistent with RvD2 bioactive concentration range.
      In both E. coli and Staphylococcus aureus infections, RvD2 limited PMN
      infiltration, enhanced phagocyte clearance of bacteria, and accelerated
      resolution. These actions were lost in GPR18-deficient mice. During PMN-mediated
      second organ injury, RvD2's protective actions were also significantly diminished
      in GPR18-deficient mice. Together, these results provide evidence for a novel
      RvD2-GPR18 resolution axis that stimulates human and mouse phagocyte functions to
      control bacterial infections and promote organ protection. 

PMID- 26195726
TI  - CHMP5 controls bone turnover rates by dampening NF-kappaB activity in
      osteoclasts.
AB  - Physiological bone remodeling requires that bone formation by osteoblasts be
      tightly coupled to bone resorption by osteoclasts. However, relatively little is
      understood about how this coupling is regulated. Here, we demonstrate that
      modulation of NF-kappaB signaling in osteoclasts via a novel activity of charged
      multivesicular body protein 5 (CHMP5) is a key determinant of systemic rates of
      bone turnover. A conditional deletion of CHMP5 in osteoclasts leads to increased
      bone resorption by osteoclasts coupled with exuberant bone formation by
      osteoblasts, resembling an early onset, polyostotic form of human Paget's disease
      of bone (PDB). These phenotypes are reversed by haploinsufficiency for Rank, as
      well as by antiresorptive treatments, including alendronate, zolendronate, and
      OPG-Fc. Accordingly, CHMP5-deficient osteoclasts display increased RANKL-induced
      NF-kappaB activation and osteoclast differentiation. Biochemical analysis
      demonstrated that CHMP5 cooperates with the PDB genetic risk factor valosin
      containing protein (VCP/p97) to stabilize the inhibitor of NF-kappaBalpha
      (IkappaBalpha), down-regulating ubiquitination of IkappaBalpha via the
      deubiquitinating enzyme USP15. Thus, CHMP5 tunes NF-kappaB signaling downstream
      of RANK in osteoclasts to dampen osteoclast differentiation, osteoblast coupling
      and bone turnover rates, and disruption of CHMP5 activity results in a PDB-like
      skeletal disorder. 

PMID- 26195727
TI  - T cell development involves TRAF3IP3-mediated ERK signaling in the Golgi.
AB  - Generation of T lymphocytes in the thymus is guided by signal transduction from
      the T cell receptor (TCR), but the underlying mechanism is incompletely
      understood. Here we have identified a Golgi-associated factor, TRAF3-interacting
      protein 3 (TRAF3IP3), as a crucial mediator of thymocyte development. TRAF3IP3
      deficiency in mice attenuates the generation of mature thymocytes caused by
      impaired thymocyte-positive selection. TRAF3IP3 mediates TCR-stimulated
      activation of the mitogen-activated protein kinase (MAPK) extracellular signal
      regulated kinase (ERK) and its upstream kinase mitogen/extracellular signal
      regulated kinase (MEK). Interestingly, TRAF3IP3 exerts this signaling function
      through recruiting MEK to the Golgi and, thereby, facilitating the interaction of
      MEK with its activator BRAF. Transgenic expression of a constitutively active MEK
      rescues the T cell development block in Traf3ip3 knockout mice. These findings
      establish TRAF3IP3 as a novel regulator of T cell development and suggest a Golgi
      specific ERK signaling mechanism that regulates thymocyte development. 

PMID- 26195728
TI  - Type 1 diacylglycerol acyltransferases of Brassica napus preferentially
      incorporate oleic acid into triacylglycerol.
AB  - DGAT1 enzymes (acyl-CoA:diacylglycerol acyltransferase 1, EC 2.3.1.20) catalyse
      the formation of triacylglycerols (TAGs), the most abundant lipids in vegetable
      oils. Thorough understanding of the enzymology of oil accumulation is critical to
      the goal of modifying oilseeds for improved vegetable oil production. Four
      isoforms of BnDGAT1, the final and rate-limiting step in triacylglycerol
      synthesis, were characterized from Brassica napus, one of the world's most
      important oilseed crops. Transcriptional profiling of developing B. napus seeds
      indicated two genes, BnDGAT1-1 and BnDGAT1-2, with high expression and two,
      BnDGAT1-3 and BnDGAT1-4, with low expression. The activities of each BnDGAT1
      isozyme were characterized following expression in a strain of yeast deficient in
      TAG synthesis. TAG from B. napus seeds contain only 10% palmitic acid (16:0) at
      the sn-3 position, so it was surprising that all four BnDGAT1 isozymes exhibited
      strong (4- to 7-fold) specificity for 16:0 over oleic acid (18:1) as the acyl-CoA
      substrate. However, the ratio of 18:1-CoA to 16:0-CoA in B. napus seeds during
      the peak period of TAG synthesis is 3:1. When substrate selectivity assays were
      conducted with 18:1-CoA and 16:0-CoA in a 3:1 ratio, the four isozymes
      incorporated 18:1 in amounts 2- to 5-fold higher than 16:0. This strong
      sensitivity of the BnDGAT1 isozymes to the relative concentrations of acyl-CoA
      substrates substantially explains the observed fatty acid composition of B. napus
      seed oil. Understanding these enzymes that are critical for triacylglycerol
      synthesis will facilitate genetic and biotechnological manipulations to improve
      this oilseed crop. 

PMID- 26195729
TI  - Peptide signalling during angiosperm seed development.
AB  - Cell-cell communication is pivotal for the coordination of various features of
      plant development. Recent studies in plants have revealed that, as in animals,
      secreted signal peptides play critical roles during reproduction. However, the
      precise signalling mechanisms in plants are not well understood. In this review,
      we discuss the known and putative roles of secreted peptides present in the seeds
      of angiosperms as key signalling factors involved in coordinating different
      aspects of seed development. 

PMID- 26195730
TI  - Expanding the repertoire of secretory peptides controlling root development with
      comparative genome analysis and functional assays.
AB  - Plant genomes encode numerous small secretory peptides (SSPs) whose functions
      have yet to be explored. Based on structural features that characterize SSP
      families known to take part in postembryonic development, this comparative genome
      analysis resulted in the identification of genes coding for oligopeptides
      potentially involved in cell-to-cell communication. Because genome annotation
      based on short sequence homology is difficult, the criteria for the de novo
      identification and aggregation of conserved SSP sequences were first benchmarked
      across five reference plant species. The resulting gene families were then
      extended to 32 genome sequences, including major crops. The global phylogenetic
      pattern common to the functionally characterized SSP families suggests that their
      apparition and expansion coincide with that of the land plants. The SSP families
      can be searched online for members, sequences and consensus
      (http://bioinformatics.psb.ugent.be/webtools/PlantSSP/). Looking for putative
      regulators of root development, Arabidopsis thaliana SSP genes were further
      selected through transcriptome meta-analysis based on their expression at
      specific stages and in specific cell types in the course of the lateral root
      formation. As an additional indication that formerly uncharacterized SSPs may
      control development, this study showed that root growth and branching were
      altered by the application of synthetic peptides matching conserved SSP motifs,
      sometimes in very specific ways. The strategy used in the study, combining
      comparative genomics, transcriptome meta-analysis and peptide functional assays
      in planta, pinpoints factors potentially involved in non-cell-autonomous
      regulatory mechanisms. A similar approach can be implemented in different species
      for the study of a wide range of developmental programmes. 

PMID- 26195732
TI  - Multiethnicity, pluralism, and migration in the south central Andes: An alternate
      path to state expansion.
AB  - The south central Andes is known as a region of enduring multiethnic diversity,
      yet it is also the cradle of one the South America's first successful expansive
      state societies. Social structures that encouraged the maintenance of separate
      identities among coexistent ethnic groups may explain this apparent
      contradiction. Although the early expansion of the Tiwanaku state (A.D. 600-1000)
      is often interpreted according to a centralized model derived from Old World
      precedents, recent archaeological research suggests a reappraisal of the socio
      political organization of Tiwanaku civilization, both for the diversity of social
      entities within its core region and for the multiple agencies behind its wider
      program of agropastoral colonization. Tiwanaku's sociopolitical pluralism in both
      its homeland and colonies tempers some of archaeology's global assumptions about
      the predominant role of centralized institutions in archaic states. 

PMID- 26195731
TI  - Hypoxia-induced force increase (HIFI) is a novel mechanism underlying the
      strengthening of labor contractions, produced by hypoxic stresses.
AB  - For successful birth, contractions need to become progressively stronger. The
      underlying mechanisms are unknown, however. We have found that a novel mechanism,
      hypoxia-induced force increase (HIFI), is switched on selectively, at term, and
      is essential to strengthening contractions. HIFI is initiated as contractions
      cyclically reduce blood flow and produce repeated hypoxic stresses, with
      associated metabolic and transcriptomic changes. The increases in contractility
      are a long-lasting, oxytocin-independent, intrinsic mechanism present only in the
      full-term pregnant uterus. HIFI is inhibited by adenosine receptor antagonism and
      blockade of cyclooxygenase-2 signaling, and partially reproduced by brief
      episodes of acidic (but not alkalotic) pH. HIFI explains how labor can progress
      despite paradoxical metabolic challenge, and provides a new mechanistic target
      for the 1 in 10 women suffering dysfunctional labor because of poor contractions.

PMID- 26195733
TI  - Global trends in infectious diseases at the wildlife-livestock interface.
AB  - The role and significance of wildlife-livestock interfaces in disease ecology has
      largely been neglected, despite recent interest in animals as origins of emerging
      diseases in humans. Scoping review methods were applied to objectively assess the
      relative interest by the scientific community in infectious diseases at
      interfaces between wildlife and livestock, to characterize animal species and
      regions involved, as well as to identify trends over time. An extensive
      literature search combining wildlife, livestock, disease, and geographical search
      terms yielded 78,861 publications, of which 15,998 were included in the analysis.
      Publications dated from 1912 to 2013 and showed a continuous increasing trend,
      including a shift from parasitic to viral diseases over time. In particular there
      was a significant increase in publications on the artiodactyls-cattle and bird
      poultry interface after 2002 and 2003, respectively. These trends could be traced
      to key disease events that stimulated public interest and research funding. Among
      the top 10 diseases identified by this review, the majority were zoonoses.
      Prominent wildlife-livestock interfaces resulted largely from interaction between
      phylogenetically closely related and/or sympatric species. The bird-poultry
      interface was the most frequently cited wildlife-livestock interface worldwide
      with other interfaces reflecting regional circumstances. This review provides the
      most comprehensive overview of research on infectious diseases at the wildlife
      livestock interface to date. 

PMID- 26195734
TI  - Quantification and real-time tracking of RNA in live cells using Sticky-flares.
AB  - We report a novel spherical nucleic acid (SNA) gold nanoparticle conjugate,
      termed the Sticky-flare, which enables facile quantification of RNA expression in
      live cells and spatiotemporal analysis of RNA transport and localization. The
      Sticky-flare is capable of entering live cells without the need for transfection
      agents and recognizing target RNA transcripts in a sequence-specific manner. On
      recognition, the Sticky-flare transfers a fluorophore-conjugated reporter to the
      transcript, resulting in a turning on of fluorescence in a quantifiable manner
      and the fluorescent labeling of targeted transcripts. The latter allows the RNA
      to be tracked via fluorescence microscopy as it is transported throughout the
      cell. We use this novel nanoconjugate to analyze the expression level and spatial
      distribution of beta-actin mRNA in HeLa cells and to observe the real-time
      transport of beta-actin mRNA in mouse embryonic fibroblasts. Furthermore, we
      investigate the application of Sticky-flares for tracking transcripts that
      undergo more extensive compartmentalization by fluorophore-labeling U1 small
      nuclear RNA and observing its distribution in the nucleus of live cells. 

PMID- 26195735
TI  - Evolutionary perspectives on clonal reproduction in vertebrate animals.
AB  - A synopsis is provided of different expressions of whole-animal vertebrate
      clonality (asexual organismal-level reproduction), both in the laboratory and in
      nature. For vertebrate taxa, such clonal phenomena include the following: human
      mediated cloning via artificial nuclear transfer; intergenerational clonality in
      nature via parthenogenesis and gynogenesis; intergenerational hemiclonality via
      hybridogenesis and kleptogenesis; intragenerational clonality via polyembryony;
      and what in effect qualifies as clonal replication via self-fertilization and
      intense inbreeding by simultaneous hermaphrodites. Each of these clonal or quasi
      clonal mechanisms is described, and its evolutionary genetic ramifications are
      addressed. By affording an atypical vantage on standard vertebrate reproduction,
      clonality offers fresh perspectives on the evolutionary and ecological
      significance of recombination-derived genetic variety. 

PMID- 26195736
TI  - Does the avoidance of sexual costs increase fitness in asexual invaders?
AB  - The high prevalence of sexual reproduction is considered a paradox mainly for two
      reasons. First, asexuals should enjoy various growth benefits because they
      seemingly rid themselves of the many inefficiencies of sexual reproduction-the so
      called costs of sex. Second, there seems to be no lack of asexual origins because
      losses of sexual reproduction have been described in almost every larger
      eukaryotic taxon. Current attempts to resolve this paradox concentrate on a few
      hypotheses that provide universal benefits that would compensate for these costs
      and give sexual reproduction a net advantage. However, are new asexual lineages
      really those powerful invaders that could quickly displace their sexual
      ancestors? Research on the costs of sex indicates that sex is often stabilized by
      highly lineage-specific mechanisms. Two main categories can be distinguished.
      First are beneficial traits that evolved within a particular species and became
      tightly associated with sex (e.g., a mating system that involves sexual
      selection, or a sexual diapausing stage that allows survival through harsh
      periods). If such traits are absent in asexuals, simple growth efficiency
      considerations will not capture the fitness benefits gained by skipping sexual
      reproduction. Second, lineage-specific factors might prevent asexuals from
      reaching their full potential (e.g., dependence on fertilization in sperm
      dependent parthenogens). Such observations suggest that the costs of sex are
      highly variable and often lower than theoretical considerations suggest. This has
      implications for the magnitude of universal benefits required to resolve the
      paradox of sex. 

PMID- 26195737
TI  - Toward a theory of punctuated subsistence change.
AB  - Discourse on the origins and spread of domesticated species focuses on universal
      causal explanations or unique regional or temporal trajectories. Despite new data
      as to the context and physical processes of early domestication, researchers
      still do not understand the types of system-level reorganizations required to
      transition from foraging to farming. Drawing upon dynamical systems theory and
      the concepts of attractors and repellors, we develop an understanding of
      subsistence transition and a description of variation in, and emergence of, human
      subsistence systems. The overlooked role of attractors and repellors in these
      systems helps explain why the origins of agriculture occurred quickly in some
      times and places, but slowly in others. A deeper understanding of the
      interactions of a limited set of variables that control the size of attractors (a
      proxy for resilience), such as population size, number of dry months, net primary
      productivity, and settlement fixity, provides new insights into the origin and
      spread of domesticated species in human economies. 

PMID- 26195738
TI  - Cloning humans? Biological, ethical, and social considerations.
AB  - There are, in mankind, two kinds of heredity: biological and cultural. Cultural
      inheritance makes possible for humans what no other organism can accomplish: the
      cumulative transmission of experience from generation to generation. In turn,
      cultural inheritance leads to cultural evolution, the prevailing mode of human
      adaptation. For the last few millennia, humans have been adapting the
      environments to their genes more often than their genes to the environments.
      Nevertheless, natural selection persists in modern humans, both as differential
      mortality and as differential fertility, although its intensity may decrease in
      the future. More than 2,000 human diseases and abnormalities have a genetic
      causation. Health care and the increasing feasibility of genetic therapy will,
      although slowly, augment the future incidence of hereditary ailments. Germ-line
      gene therapy could halt this increase, but at present, it is not technically
      feasible. The proposal to enhance the human genetic endowment by genetic cloning
      of eminent individuals is not warranted. Genomes can be cloned; individuals
      cannot. In the future, therapeutic cloning will bring enhanced possibilities for
      organ transplantation, nerve cells and tissue healing, and other health benefits.

PMID- 26195739
TI  - Music training alters the course of adolescent auditory development.
AB  - Fundamental changes in brain structure and function during adolescence are well
      characterized, but the extent to which experience modulates adolescent
      neurodevelopment is not. Musical experience provides an ideal case for examining
      this question because the influence of music training begun early in life is well
      known. We investigated the effects of in-school music training, previously shown
      to enhance auditory skills, versus another in-school training program that did
      not focus on development of auditory skills (active control). We tested
      adolescents on neural responses to sound and language skills before they entered
      high school (pretraining) and again 3 y later. Here, we show that in-school music
      training begun in high school prolongs the stability of subcortical sound
      processing and accelerates maturation of cortical auditory responses. Although
      phonological processing improved in both the music training and active control
      groups, the enhancement was greater in adolescents who underwent music training.
      Thus, music training initiated as late as adolescence can enhance neural
      processing of sound and confer benefits for language skills. These results
      establish the potential for experience-driven brain plasticity during adolescence
      and demonstrate that in-school programs can engender these changes. 

PMID- 26195740
TI  - RNA helicase HEL-1 promotes longevity by specifically activating DAF-16/FOXO
      transcription factor signaling in Caenorhabditis elegans.
AB  - The homeostatic maintenance of the genomic DNA is crucial for regulating aging
      processes. However, the role of RNA homeostasis in aging processes remains
      unknown. RNA helicases are a large family of enzymes that regulate the biogenesis
      and homeostasis of RNA. However, the functional significance of RNA helicases in
      aging has not been explored. Here, we report that a large fraction of RNA
      helicases regulate the lifespan of Caenorhabditis elegans. In particular, we show
      that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by
      specifically activating the DAF-16/forkhead box O (FOXO) transcription factor
      signaling pathway. We find that HEL-1 is required for the longevity conferred by
      reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is
      sufficient for extending lifespan. We further show that the expression of HEL-1
      in the intestine and neurons contributes to longevity. HEL-1 enhances the
      induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL
      1 appears to promote longevity in response to decreased IIS as a transcription
      coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a
      similar mechanism for longevity regulation via an RNA helicase-dependent
      regulation of FOXO signaling may operate in mammals, including humans. 

PMID- 26195741
TI  - Small-molecule enhancers of autophagy modulate cellular disease phenotypes
      suggested by human genetics.
AB  - Studies of human genetics and pathophysiology have implicated the regulation of
      autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These
      findings have motivated the use of small-molecule probes to study how modulation
      of autophagy affects disease-associated phenotypes. Here, we describe the
      discovery of the small-molecule probe BRD5631 that is derived from diversity
      oriented synthesis and enhances autophagy through an mTOR-independent pathway. We
      demonstrate that BRD5631 affects several cellular disease phenotypes previously
      linked to autophagy, including protein aggregation, cell survival, bacterial
      replication, and inflammatory cytokine production. BRD5631 can serve as a
      valuable tool for studying the role of autophagy in the context of cellular
      homeostasis and disease. 

PMID- 26195742
TI  - Replacing SNAP-25b with SNAP-25a expression results in metabolic disease.
AB  - Synaptosomal-associated protein of 25 kDa (SNAP-25) is a key molecule in the
      soluble N-ethylmaleimide-sensitive factor attachment protein (SNARE) complex
      mediating fast Ca(2+)-triggered release of hormones and neurotransmitters, and
      both splice variants, SNAP-25a and SNAP-25b, can participate in this process.
      Here we explore the hypothesis that minor alterations in the machinery mediating
      regulated membrane fusion can increase the susceptibility for metabolic disease
      and precede obesity and type 2 diabetes. Thus, we used a mouse mutant engineered
      to express normal levels of SNAP-25 but only SNAP-25a. These SNAP-25b-deficient
      mice were exposed to either a control or a high-fat/high-sucrose diet. Monitoring
      of food intake, body weight, hypothalamic function, and lipid and glucose
      homeostases showed that SNAP-25b-deficient mice fed with control diet developed
      hyperglycemia, liver steatosis, and adipocyte hypertrophy, conditions
      dramatically exacerbated when combined with the high-fat/high-sucrose diet. Thus,
      modified SNARE function regulating stimulus-dependent exocytosis can increase the
      vulnerability to and even provoke metabolic disease. When combined with a high
      fat/high-sucrose diet, this vulnerability resulted in diabesity. Our SNAP-25b
      deficient mouse may represent a diabesity model. 

PMID- 26195743
TI  - Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating
      device (NE2RD) for diagnostics.
AB  - Recent advances in biosensing technologies present great potential for medical
      diagnostics, thus improving clinical decisions. However, creating a label-free
      general sensing platform capable of detecting multiple biotargets in various
      clinical specimens over a wide dynamic range, without lengthy sample-processing
      steps, remains a considerable challenge. In practice, these barriers prevent
      broad applications in clinics and at patients' homes. Here, we demonstrate the
      nanoplasmonic electrical field-enhanced resonating device (NE(2)RD), which
      addresses all these impediments on a single platform. The NE(2)RD employs an
      immunodetection assay to capture biotargets, and precisely measures spectral
      color changes by their wavelength and extinction intensity shifts in
      nanoparticles without prior sample labeling or preprocessing. We present through
      multiple examples, a label-free, quantitative, portable, multitarget platform by
      rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria,
      eukaryotic cells, and distinct viruses. The linear dynamic range of NE(2)RD is
      five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL
      This range and sensitivity are achieved by self-assembling gold nanoparticles to
      generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We
      demonstrate that this precise platform handles multiple clinical samples such as
      whole blood, serum, and saliva without sample preprocessing under diverse
      conditions of temperature, pH, and ionic strength. The NE(2)RD's broad dynamic
      range, detection limit, and portability integrated with a disposable fluidic chip
      have broad applications, potentially enabling the transition toward precision
      medicine at the point-of-care or primary care settings and at patients' homes. 

PMID- 26195744
TI  - Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells
      associated with protective immunity.
AB  - Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis,
      and correlates of protection from severe dengue disease and vaccine efficacy have
      not yet been established. Although DENV-specific CD8(+) T-cell responses have
      been extensively studied, the breadth and specificity of CD4(+) T-cell responses
      remains to be defined. Here we define HLA-restricted CD4(+) T-cell epitopes
      resulting from natural infection with dengue virus in a hyperepidemic setting. Ex
      vivo flow-cytometric analysis of DENV-specific CD4(+) T cells revealed that the
      virus-specific cells were highly polarized, with a strong bias toward a CX3CR1(+)
      Eomesodermin(+) perforin(+) granzyme B(+) CD45RA(+) CD4 CTL phenotype.
      Importantly, these cells correlated with a protective HLA DR allele, and we
      demonstrate that these cells have direct ex vivo DENV-specific cytolytic
      activity. We speculate that cytotoxic dengue-specific CD4(+) T cells may play a
      role in the control of dengue infection in vivo, and this immune correlate may be
      a key target for dengue virus vaccine development. 

PMID- 26195745
TI  - Stem cells are units of natural selection for tissue formation, for germline
      development, and in cancer development.
AB  - It is obvious that natural selection operates at the level of individuals and
      collections of individuals. Nearly two decades ago we showed that in multi
      individual colonies of protochordate colonial tunicates sharing a blood
      circulation, there exists an exchange of somatic stem cells and germline stem
      cells, resulting in somatic chimeras and stem cell competitions for gonadal
      niches. Stem cells are unlike other cells in the body in that they alone self
      renew, so that they form clones that are perpetuated for the life of the
      organism. Stem cell competitions have allowed the emergence of competitive
      somatic and germline stem cell clones. Highly successful germline stem cells
      usually outcompete less successful competitors both in the gonads of the genotype
      partner from which they arise and in the gonads of the natural parabiotic
      partners. Therefore, natural selection also operates at the level of germline
      stem cell clones. In the colonial tunicate Botryllus schlosseri the formation of
      natural parabionts is prevented by a single-locus highly polymorphic
      histocompatibility gene called Botryllus histocompatibility factor. This limits
      germline stem cell predation to kin, as the locus has hundreds of alleles. We
      show that in mice germline stem cells compete for gonad niches, and in mice and
      humans, blood-forming stem cells also compete for bone marrow niches. We show
      that the clonal progression from blood-forming stem cells to acute leukemias by
      successive genetic and epigenetic events in blood stem cells also involves
      competition and selection between clones and propose that this is a general theme
      in cancer. 

PMID- 26195747
TI  - Influences of clonality on plant sexual reproduction.
AB  - Flowering plants possess an unrivaled diversity of mechanisms for achieving
      sexual and asexual reproduction, often simultaneously. The commonest type of
      asexual reproduction is clonal growth (vegetative propagation) in which parental
      genotypes (genets) produce vegetative modules (ramets) that are capable of
      independent growth, reproduction, and often dispersal. Clonal growth leads to an
      expansion in the size of genets and increased fitness because large floral
      displays increase fertility and opportunities for outcrossing. Moreover, the
      clonal dispersal of vegetative propagules can assist "mate finding," particularly
      in aquatic plants. However, there are ecological circumstances in which
      functional antagonism between sexual and asexual reproductive modes can
      negatively affect the fitness of clonal plants. Populations of heterostylous and
      dioecious species have a small number of mating groups (two or three), which
      should occur at equal frequency in equilibrium populations. Extensive clonal
      growth and vegetative dispersal can disrupt the functioning of these sexual
      polymorphisms, resulting in biased morph ratios and populations with a single
      mating group, with consequences for fertility and mating. In populations in which
      clonal propagation predominates, mutations reducing fertility may lead to sexual
      dysfunction and even the loss of sex. Recent evidence suggests that somatic
      mutations can play a significant role in influencing fitness in clonal plants and
      may also help explain the occurrence of genetic diversity in sterile clonal
      populations. Highly polymorphic genetic markers offer outstanding opportunities
      for gaining novel insights into functional interactions between sexual and clonal
      reproduction in flowering plants. 

PMID- 26195746
TI  - Sex is a ubiquitous, ancient, and inherent attribute of eukaryotic life.
AB  - Sexual reproduction and clonality in eukaryotes are mostly seen as exclusive, the
      latter being rather exceptional. This view might be biased by focusing almost
      exclusively on metazoans. We analyze and discuss reproduction in the context of
      extant eukaryotic diversity, paying special attention to protists. We present
      results of phylogenetically extended searches for homologs of two proteins
      functioning in cell and nuclear fusion, respectively (HAP2 and GEX1), providing
      indirect evidence for these processes in several eukaryotic lineages where sex
      has not been observed yet. We argue that (i) the debate on the relative
      significance of sex and clonality in eukaryotes is confounded by not
      appropriately distinguishing multicellular and unicellular organisms; (ii)
      eukaryotic sex is extremely widespread and already present in the last eukaryotic
      common ancestor; and (iii) the general mode of existence of eukaryotes is best
      described by clonally propagating cell lines with episodic sex triggered by
      external or internal clues. However, important questions concern the relative
      longevity of true clonal species (i.e., species not able to return to sexual
      procreation anymore). Long-lived clonal species seem strikingly rare. We analyze
      their properties in the light of meiotic sex development from existing
      prokaryotic repair mechanisms. Based on these considerations, we speculate that
      eukaryotic sex likely developed as a cellular survival strategy, possibly in the
      context of internal reactive oxygen species stress generated by a (proto)
      mitochondrion. Thus, in the context of the symbiogenic model of eukaryotic
      origin, sex might directly result from the very evolutionary mode by which
      eukaryotic cells arose. 

PMID- 26195748
TI  - Consequences of clonality for sexual fitness: Clonal expansion enhances fitness
      under spatially restricted dispersal.
AB  - Clonality is a pervasive feature of sessile organisms, but this form of asexual
      reproduction is thought to interfere with sexual fitness via the movement of
      gametes among the modules that comprise the clone. This within-clone movement of
      gametes is expected to reduce sexual fitness via mate limitation of male
      reproductive success and, in some cases, via the production of highly inbred
      (i.e., self-fertilized) offspring. However, clonality also results in the spatial
      expansion of the genetic individual (i.e., genet), and this should decrease
      distances gametes and sexually produced offspring must travel to avoid competing
      with other gametes and offspring from the same clone. The extent to which any
      negative effects of clonality on mating success might be offset by the positive
      effects of spatial expansion is poorly understood. Here, we develop spatially
      explicit models in which fitness was determined by the success of genets through
      their male and female sex functions. Our results indicate that clonality serves
      to increase sexual fitness when it is associated with the outward expansion of
      the genet. Our models further reveal that the main fitness benefit of clonal
      expansion might occur through the dispersal of offspring over a wider area
      compared with nonclonal phenotypes. We conclude that, instead of interfering with
      sexual reproduction, clonal expansion should often serve to enhance sexual
      fitness. 

PMID- 26195749
TI  - Impermanence of bacterial clones.
AB  - Bacteria reproduce asexually and pass on a single genome copied from the parent,
      a reproductive mode that assures the clonal descent of progeny; however, a truly
      clonal bacterial species is extremely rare. The signal of clonality can be
      interrupted by gene uptake and exchange, initiating homologous recombination that
      results in the unique sequence of one clone being incorporated into another.
      Because recombination occurs sporadically and on local scales, these events are
      often difficult to recognize, even when considering large samples of completely
      sequenced genomes. Moreover, several processes can produce the appearance of
      clonality in populations that undergo frequent recombination. The rates and
      consequences of recombination have been studied in Escherichia coli for over 40
      y, and, during this time, there have been several shifting views of its clonal
      status, population structure, and rates of gene exchange. We reexamine the
      studies and retrace the evolution of the methods that have assessed the extent of
      DNA flux, largely focusing on its impact on the E. coli genome. 

PMID- 26195750
TI  - Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary
      tumors of the brain and spinal cord.
AB  - Cell-free DNA shed by cancer cells has been shown to be a rich source of putative
      tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord
      tumors cannot usually be detected in the blood, we studied whether the
      cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here
      termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one
      mutation in each tumor using targeted or genome-wide sequencing. Using these
      patient-specific mutations as biomarkers, we identified detectable levels of CSF
      tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All
      medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space
      were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was
      detected in patients whose tumors were not directly adjacent to a CSF reservoir
      (P < 0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be
      useful for the management of patients with primary tumors of the brain or spinal
      cord. 

PMID- 26195751
TI  - Preventing clonal evolutionary processes in cancer: Insights from mathematical
      models.
AB  - Clonal evolutionary processes can drive pathogenesis in human diseases, with
      cancer being a prominent example. To prevent or treat cancer, mechanisms that can
      potentially interfere with clonal evolutionary processes need to be understood
      better. Mathematical modeling is an important research tool that plays an ever
      increasing role in cancer research. This paper discusses how mathematical models
      can be useful to gain insights into mechanisms that can prevent disease
      initiation, help analyze treatment responses, and aid in the design of treatment
      strategies to combat the emergence of drug-resistant cells. The discussion will
      be done in the context of specific examples. Among defense mechanisms, we explore
      how replicative limits and cellular senescence induced by telomere shortening can
      influence the emergence and evolution of tumors. Among treatment approaches, we
      consider the targeted treatment of chronic lymphocytic leukemia (CLL) with
      tyrosine kinase inhibitors. We illustrate how basic evolutionary mathematical
      models have the potential to make patient-specific predictions about disease and
      treatment outcome, and argue that evolutionary models could become important
      clinical tools in the field of personalized medicine. 

PMID- 26195752
TI  - Reduced transmission of human schistosomiasis after restoration of a native river
      prawn that preys on the snail intermediate host.
AB  - Eliminating human parasitic disease often requires interrupting complex
      transmission pathways. Even when drugs to treat people are available, disease
      control can be difficult if the parasite can persist in nonhuman hosts. Here, we
      show that restoration of a natural predator of a parasite's intermediate hosts
      may enhance drug-based schistosomiasis control. Our study site was the Senegal
      River Basin, where villagers suffered a massive outbreak and persistent epidemic
      after the 1986 completion of the Diama Dam. The dam blocked the annual migration
      of native river prawns (Macrobrachium vollenhoveni) that are voracious predators
      of the snail intermediate hosts for schistosomiasis. We tested schistosomiasis
      control by reintroduced river prawns in a before-after-control-impact field
      experiment that tracked parasitism in snails and people at two matched villages
      after prawns were stocked at one village's river access point. The abundance of
      infected snails was 80% lower at that village, presumably because prawn predation
      reduced the abundance and average life span of latently infected snails. As
      expected from a reduction in infected snails, human schistosomiasis prevalence
      was 18 +/- 5% lower and egg burden was 50 +/- 8% lower at the prawn-stocking
      village compared with the control village. In a mathematical model of the system,
      stocking prawns, coupled with infrequent mass drug treatment, eliminates
      schistosomiasis from high-transmission sites. We conclude that restoring river
      prawns could be a novel contribution to controlling, or eliminating,
      schistosomiasis. 

PMID- 26195753
TI  - Heterogeneous binding of the SH3 client protein to the DnaK molecular chaperone.
AB  - The molecular chaperone heat shock protein 70 (Hsp70) plays a vital role in
      cellular processes, including protein folding and assembly, and helps prevent
      aggregation under physiological and stress-related conditions. Although the
      structural changes undergone by full-length client proteins upon interaction with
      DnaK (i.e., Escherichia coli Hsp70) are fundamental to understand chaperone
      mediated protein folding, these changes are still largely unexplored. Here, we
      show that multiple conformations of the SRC homology 3 domain (SH3) client
      protein interact with the ADP-bound form of the DnaK chaperone. Chaperone-bound
      SH3 is largely unstructured yet distinct from the unfolded state in the absence
      of DnaK. The bound client protein shares a highly flexible N terminus and
      multiple slowly interconverting conformations in different parts of the sequence.
      In all, there is significant structural and dynamical heterogeneity in the DnaK
      bound client protein, revealing that proteins may undergo some conformational
      sampling while chaperone-bound. This result is important because it shows that
      the surface of the Hsp70 chaperone provides an aggregation-free environment able
      to support part of the search for the native state. 

PMID- 26195754
TI  - How amide hydrogens exchange in native proteins.
AB  - Amide hydrogen exchange (HX) is widely used in protein biophysics even though our
      ignorance about the HX mechanism makes data interpretation imprecise. Notably,
      the open exchange-competent conformational state has not been identified. Based
      on analysis of an ultralong molecular dynamics trajectory of the protein BPTI, we
      propose that the open (O) states for amides that exchange by subglobal
      fluctuations are locally distorted conformations with two water molecules
      directly coordinated to the N-H group. The HX protection factors computed from
      the relative O-state populations agree well with experiment. The O states of
      different amides show little or no temporal correlation, even if adjacent
      residues unfold cooperatively. The mean residence time of the O state is ~100 ps
      for all examined amides, so the large variation in measured HX rate must be
      attributed to the opening frequency. A few amides gain solvent access via tunnels
      or pores penetrated by water chains including native internal water molecules,
      but most amides access solvent by more local structural distortions. In either
      case, we argue that an overcoordinated N-H group is necessary for efficient
      proton transfer by Grotthuss-type structural diffusion. 

PMID- 26195755
TI  - In the light of evolution IX: Clonal reproduction: Alternatives to sex.

PMID- 26195756
TI  - Toward an evolutionary model of cancer: Considering the mechanisms that govern
      the fate of somatic mutations.
AB  - Our understanding of cancer has greatly advanced since Nordling [Nordling CO
      (1953) Br J Cancer 7(1):68-72] and Armitage and Doll [Armitage P, Doll R (1954)
      Br J Cancer 8(1):1-12] put forth the multistage model of carcinogenesis. However,
      a number of observations remain poorly understood from the standpoint of this
      paradigm in its contemporary state. These observations include the similar age
      dependent exponential rise in incidence of cancers originating from
      stem/progenitor pools differing drastically in size, age-dependent cell division
      profiles, and compartmentalization. This common incidence pattern is
      characteristic of cancers requiring different numbers of oncogenic mutations, and
      it scales to very divergent life spans of mammalian species. Also, bigger mammals
      with larger underlying stem cell pools are not proportionally more prone to
      cancer, an observation known as Peto's paradox. Here, we present a number of
      factors beyond the occurrence of oncogenic mutations that are unaccounted for in
      the current model of cancer development but should have significant impacts on
      cancer incidence. Furthermore, we propose a revision of the current understanding
      for how oncogenic and other functional somatic mutations affect cellular fitness.
      We present evidence, substantiated by evolutionary theory, demonstrating that
      fitness is a dynamic environment-dependent property of a phenotype and that
      oncogenic mutations should have vastly different fitness effects on somatic cells
      dependent on the tissue microenvironment in an age-dependent manner. Combined,
      this evidence provides a firm basis for understanding the age-dependent incidence
      of cancers as driven by age-altered systemic processes regulated above the cell
      level. 

PMID- 26195757
TI  - Impact of fossil fuel emissions on atmospheric radiocarbon and various
      applications of radiocarbon over this century.
AB  - Radiocarbon analyses are commonly used in a broad range of fields, including
      earth science, archaeology, forgery detection, isotope forensics, and physiology.
      Many applications are sensitive to the radiocarbon ((14)C) content of atmospheric
      CO2, which has varied since 1890 as a result of nuclear weapons testing, fossil
      fuel emissions, and CO2 cycling between atmospheric, oceanic, and terrestrial
      carbon reservoirs. Over this century, the ratio (14)C/C in atmospheric CO2
      (Delta(14)CO2) will be determined by the amount of fossil fuel combustion, which
      decreases Delta(14)CO2 because fossil fuels have lost all (14)C from radioactive
      decay. Simulations of Delta(14)CO2 using the emission scenarios from the
      Intergovernmental Panel on Climate Change Fifth Assessment Report, the
      Representative Concentration Pathways, indicate that ambitious emission
      reductions could sustain Delta(14)CO2 near the preindustrial level of 00/00
      through 2100, whereas "business-as-usual" emissions will reduce Delta(14)CO2 to 
      2500/00, equivalent to the depletion expected from over 2,000 y of radioactive
      decay. Given current emissions trends, fossil fuel emission-driven artificial
      "aging" of the atmosphere is likely to occur much faster and with a larger
      magnitude than previously expected. This finding has strong and as yet
      unrecognized implications for many applications of radiocarbon in various fields,
      and it implies that radiocarbon dating may no longer provide definitive ages for
      samples up to 2,000 y old. 

PMID- 26195759
TI  - Plasmid replication initiator interactions with origin 13-mers and polymerase
      subunits contribute to strand-specific replisome assembly.
AB  - Although the molecular basis for replisome activity has been extensively
      investigated, it is not clear what the exact mechanism for de novo assembly of
      the replication complex at the replication origin is, or how the directionality
      of replication is determined. Here, using the plasmid RK2 replicon, we analyze
      the protein interactions required for Escherichia coli polymerase III (Pol III)
      holoenzyme association at the replication origin. Our investigations revealed
      that in E. coli, replisome formation at the plasmid origin involves interactions
      of the RK2 plasmid replication initiation protein (TrfA) with both the polymerase
      beta- and alpha-subunits. In the presence of other replication proteins,
      including DnaA, helicase, primase and the clamp loader, TrfA interaction with the
      beta-clamp contributes to the formation of the beta-clamp nucleoprotein complex
      on origin DNA. By reconstituting in vitro the replication reaction on ssDNA
      templates, we demonstrate that TrfA interaction with the beta-clamp and sequence
      specific TrfA interaction with one strand of the plasmid origin DNA unwinding
      element (DUE) contribute to strand-specific replisome assembly. Wild-type TrfA,
      but not the TrfA QLSLF mutant (which does not interact with the beta-clamp), in
      the presence of primase, helicase, Pol III core, clamp loader, and beta-clamp
      initiates DNA synthesis on ssDNA template containing 13-mers of the bottom
      strand, but not the top strand, of DUE. Results presented in this work uncovered
      requirements for anchoring polymerase at the plasmid replication origin and bring
      insights of how the directionality of DNA replication is determined. 

PMID- 26195758
TI  - Prospective isolation of human erythroid lineage-committed progenitors.
AB  - Determining the developmental pathway leading to erythrocytes and being able to
      isolate their progenitors are crucial to understanding and treating disorders of
      red cell imbalance such as anemia, myelodysplastic syndrome, and polycythemia
      vera. Here we show that the human erythrocyte progenitor (hEP) can be
      prospectively isolated from adult bone marrow. We found three subfractions that
      possessed different expression patterns of CD105 and CD71 within the previously
      defined human megakaryocyte/erythrocyte progenitor (hMEP; Lineage(-) CD34(+)
      CD38(+) IL-3Ralpha(-) CD45RA(-)) population. Both CD71(-) CD105(-) and CD71(+)
      CD105(-) MEPs, at least in vitro, still retained bipotency for the megakaryocyte
      (MegK) and erythrocyte (E) lineages, although the latter subpopulation is skewed
      in differentiation toward the erythroid lineage. Notably, the proliferative and
      differentiation output of the CD71(intermediate(int)/+) CD105(+) subset of cells
      within the MEP population was completely restricted to the erythroid lineage with
      the loss of MegK potential. CD71(+) CD105(-) MEPs are erythrocyte-biased MEPs (E
      MEPs) and CD71(int/+) CD105(+) cells are EPs. These previously unclassified
      populations may facilitate further understanding of the molecular mechanisms
      governing human erythroid development and serve as potential therapeutic targets
      in disorders of the erythroid lineage. 

PMID- 26195761
TI  - Study of the instability of the Poiseuille flow using a thermodynamic formalism.
AB  - The stability of the plane Poiseuille flow is analyzed using a thermodynamic
      formalism by considering the deterministic Navier-Stokes equation with Gaussian
      random initial data. A unique critical Reynolds number, Rec ~ 2,332, at which the
      probability of observing puffs in the solution changes from 0 to 1, is
      numerically demonstrated to exist in the thermodynamic limit and is found to be
      independent of the noise amplitude. Using the puff density as the macrostate
      variable, the free energy of such a system is computed and analyzed. The puff
      density approaches zero as the critical Reynolds number is approached from above,
      signaling a continuous transition despite the fact that the bifurcation is
      subcritical for a finite-sized system. An action function is found for the
      probability of observing puffs in a small subregion of the flow, and this action
      function depends only on the Reynolds number. The strategy used here should be
      applicable to a wide range of other problems exhibiting subcritical
      instabilities.

PMID- 26195760
TI  - Complement membrane attack complexes activate noncanonical NF-kappaB by forming
      an Akt+ NIK+ signalosome on Rab5+ endosomes.
AB  - Complement membrane attack complexes (MACs) promote inflammatory functions in
      endothelial cells (ECs) by stabilizing NF-kappaB-inducing kinase (NIK) and
      activating noncanonical NF-kappaB signaling. Here we report a novel endosome
      based signaling complex induced by MACs to stabilize NIK. We found that, in
      contrast to cytokine-mediated activation, NIK stabilization by MACs did not
      involve cIAP2 or TRAF3. Informed by a genome-wide siRNA screen, instead this
      response required internalization of MACs in a clathrin-, AP2-, and dynamin
      dependent manner into Rab5(+)endosomes, which recruited activated Akt, stabilized
      NIK, and led to phosphorylation of IkappaB kinase (IKK)-alpha. Active Rab5 was
      required for recruitment of activated Akt to MAC(+) endosomes, but not for MAC
      internalization or for Akt activation. Consistent with these in vitro
      observations, MAC internalization occurred in human coronary ECs in vivo and was
      similarly required for NIK stabilization and EC activation. We conclude that MACs
      activate noncanonical NF-kappaB by forming a novel Akt(+)NIK(+) signalosome on
      Rab5(+) endosomes. 

PMID- 26195762
TI  - Force generation by the growth of amyloid aggregates.
AB  - The generation of mechanical forces are central to a wide range of vital
      biological processes, including the function of the cytoskeleton. Although the
      forces emerging from the polymerization of native proteins have been studied in
      detail, the potential for force generation by aberrant protein polymerization has
      not yet been explored. Here, we show that the growth of amyloid fibrils,
      archetypical aberrant protein polymers, is capable of unleashing mechanical
      forces on the piconewton scale for individual filaments. We apply microfluidic
      techniques to measure the forces released by amyloid growth for two systems:
      insulin and lysozyme. The level of force measured for amyloid growth in both
      systems is comparable to that observed for actin and tubulin, systems that have
      evolved to generate force during their native functions and, unlike amyloid
      growth, rely on the input of external energy in the form of nucleotide hydrolysis
      for maximum force generation. Furthermore, we find that the power density
      released from growing amyloid fibrils is comparable to that of high-performance
      synthetic polymer actuators. These findings highlight the potential of amyloid
      structures as active materials and shed light on the criteria for regulation and
      reversibility that guide molecular evolution of functional polymers. 

PMID- 26195763
TI  - The lameness of King Philip II and Royal Tomb I at Vergina, Macedonia.
AB  - King Philip II was the father of Alexander the Great. He suffered a notorious
      penetrating wound by a lance through his leg that was nearly fatal and left him
      lame in 339 B.C.E. (i.e., 3 y before his assassination in 336 B.C.E.). In 1977
      and 1978 two male skeletons were excavated in the Royal Tombs II and I of
      Vergina, Greece, respectively. Tomb I also contained another adult (likely a
      female) and a newborn skeleton. The current view is that Philip II was buried in
      Tomb II. However, the male skeleton of Tomb II bears no lesions to his legs that
      would indicate lameness. We investigated the skeletal material of Tomb I with
      modern forensic techniques. The male individual in Tomb I displays a conspicuous
      case of knee ankylosis that is conclusive evidence of lameness. Right through the
      overgrowth of the knee, there is a hole. There are no obvious signs that are
      characteristic of infection and osteomyelitis. This evidence indicates that the
      injury was likely caused by a severe penetrating wound to the knee, which
      resulted in an active inflammatory process that stopped years before death.
      Standard anthropological age-estimation techniques based on dry bone, epiphyseal
      lines, and tooth analysis gave very wide age ranges for the male, centered around
      45 y. The female would be around 18-y-old and the infant would be a newborn. It
      is concluded that King Philip II, his wife Cleopatra, and their newborn child are
      the occupants of Tomb I. 

PMID- 26195764
TI  - Norbin ablation results in defective adult hippocampal neurogenesis and
      depressive-like behavior in mice.
AB  - Adult neurogenesis in the hippocampus subgranular zone is associated with the
      etiology and treatment efficiency of depression. Factors that affect adult
      hippocampal neurogenesis have been shown to contribute to the neuropathology of
      depression. Glutamate, the major excitatory neurotransmitter, plays a critical
      role in different aspects of neurogenesis. Of the eight metabotropic glutamate
      receptors (mGluRs), mGluR5 is the most highly expressed in neural stem cells. We
      previously identified Norbin as a positive regulator of mGluR5 and showed that
      its expression promotes neurite outgrowth. In this study, we investigated the
      role of Norbin in adult neurogenesis and depressive-like behaviors using Norbin
      deficient mice. We found that Norbin deletion significantly reduced hippocampal
      neurogenesis; specifically, the loss of Norbin impaired the proliferation and
      maturation of newborn neurons without affecting cell-fate specification of neural
      stem cells/neural progenitor cells (NSCs/NPCs). Norbin is highly expressed in the
      granular neurons in the dentate gyrus of the hippocampus, but it is undetectable
      in NSCs/NPCs or immature neurons, suggesting that the effect of Norbin on
      neurogenesis is likely caused by a nonautonomous niche effect. In support of this
      hypothesis, we found that the expression of a cell-cell contact gene,
      Desmoplakin, is greatly reduced in Norbin-deletion mice. Moreover, Norbin-KO mice
      show an increased immobility in the forced-swim test and the tail-suspension test
      and reduced sucrose preference compared with wild-type controls. Taken together,
      these results show that Norbin is a regulator of adult hippocampal neurogenesis
      and that its deletion causes depressive-like behaviors. 

PMID- 26195765
TI  - A genetic basis of variation in eccrine sweat gland and hair follicle density.
AB  - Among the unique features of humans, one of the most salient is the ability to
      effectively cool the body during extreme prolonged activity through the
      evapotranspiration of water on the skin's surface. The evolution of this novel
      physiological ability required a dramatic increase in the density and
      distribution of eccrine sweat glands relative to other mammals and a concomitant
      reduction of body hair cover. Elucidation of the genetic underpinnings for these
      adaptive changes is confounded by a lack of knowledge about how eccrine gland
      fate and density are specified during development. Moreover, although reciprocal
      changes in hair cover and eccrine gland density are required for efficient
      thermoregulation, it is unclear if these changes are linked by a common genetic
      regulation. To identify pathways controlling the relative patterning of eccrine
      glands and hair follicles, we exploited natural variation in the density of these
      organs between different strains of mice. Quantitative trait locus mapping
      identified a large region on mouse Chromosome 1 that controls both hair and
      eccrine gland densities. Differential and allelic expression analysis of the
      genes within this interval coupled with subsequent functional studies
      demonstrated that the level of En1 activity directs the relative numbers of
      eccrine glands and hair follicles. These findings implicate En1 as a newly
      identified and reciprocal determinant of hair follicle and eccrine gland density
      and identify a pathway that could have contributed to the evolution of the unique
      features of human skin. 

PMID- 26195766
TI  - How clonal are Neisseria species? The epidemic clonality model revisited.
AB  - The three species Neisseria meningitidis, Neisseria gonorrheae, and Neisseria
      lactamica are often regarded as highly recombining bacteria. N. meningitidis has
      been considered a paradigmatic case of the "semiclonal model" or of "epidemic
      clonality," demonstrating occasional bouts of clonal propagation in an otherwise
      recombining species. In this model, occasional clonality generates linkage
      disequilibrium in the short term. In the long run, however, the effects of
      clonality are countered by recombination. We show that many data are at odds with
      this proposal and that N. meningitidis fits the criteria that we have proposed
      for predominant clonal evolution (PCE). We point out that (i) the proposed way to
      distinguish epidemic clonality from PCE may be faulty and (ii) the evidence of
      deep phylogenies by microarrays and whole-genome sequencing is at odds with the
      predictions of the semiclonal model. Last, we revisit the species status of N.
      meningitidis, N. gonorrheae, and N. lactamica in the light of the PCE model. 

PMID- 26195768
TI  - Toward a sustainable biomedical research enterprise: Finding consensus and
      implementing recommendations.
AB  - The US research enterprise is under significant strain due to stagnant funding,
      an expanding workforce, and complex regulations that increase costs and slow the
      pace of research. In response, a number of groups have analyzed the problems and
      offered recommendations for resolving these issues. However, many of these
      recommendations lacked follow-up implementation, allowing the damage of stagnant
      funding and outdated policies to persist. Here, we analyze nine reports published
      since the beginning of 2012 and consolidate over 250 suggestions into eight
      consensus recommendations made by the majority of the reports. We then propose
      how to implement these consensus recommendations, and we identify critical
      issues, such as improving workforce diversity and stakeholder interactions, on
      which the community has yet to achieve consensus. 

PMID- 26195767
TI  - Erlotinib protects against LPS-induced endotoxicity because TLR4 needs EGFR to
      signal.
AB  - Several components of the canonical pathway of response to lipopolysaccharide
      (LPS) are required for the EGF-dependent activation of NFkappaB. Conversely, the
      ability of Toll-like Receptor 4 (TLR4) to activate NFkappaB in response to LPS is
      impaired by down regulating EGF receptor (EGFR) expression or by using the EGFR
      inhibitor erlotinib. The LYN proto-oncogene (LYN) is required for signaling in
      both directions. LYN binds to the EGFR upon LPS stimulation, and erlotinib
      impairs this association. In mice, erlotinib blocks the LPS-induced expression of
      tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) and ameliorates
      LPS-induced endotoxity, revealing that EGFR is essential for LPS-induced
      signaling in vivo. 

PMID- 26195769
TI  - Stress controls the mechanics of collagen networks.
AB  - Collagen is the main structural and load-bearing element of various connective
      tissues, where it forms the extracellular matrix that supports cells. It has long
      been known that collagenous tissues exhibit a highly nonlinear stress-strain
      relationship, although the origins of this nonlinearity remain unknown. Here, we
      show that the nonlinear stiffening of reconstituted type I collagen networks is
      controlled by the applied stress and that the network stiffness becomes
      surprisingly insensitive to network concentration. We demonstrate how a simple
      model for networks of elastic fibers can quantitatively account for the mechanics
      of reconstituted collagen networks. Our model points to the important role of
      normal stresses in determining the nonlinear shear elastic response, which can
      explain the approximate exponential relationship between stress and strain
      reported for collagenous tissues. This further suggests principles for the design
      of synthetic fiber networks with collagen-like properties, as well as a mechanism
      for the control of the mechanics of such networks. 

PMID- 26195771
TI  - Quantum dimer model for the pseudogap metal.
AB  - We propose a quantum dimer model for the metallic state of the hole-doped
      cuprates at low hole density, p. The Hilbert space is spanned by spinless,
      neutral, bosonic dimers and spin S = 1/2, charge +e fermionic dimers. The model
      realizes a "fractionalized Fermi liquid" with no symmetry breaking and small hole
      pocket Fermi surfaces enclosing a total area determined by p. Exact
      diagonalization, on lattices of sizes up to 8 * 8, shows anisotropic
      quasiparticle residue around the pocket Fermi surfaces. We discuss the
      relationship to experiments.

PMID- 26195770
TI  - Artificial cloning of domestic animals.
AB  - Domestic animals can be cloned using techniques such as embryo splitting and
      nuclear transfer to produce genetically identical individuals. Although embryo
      splitting is limited to the production of only a few identical individuals,
      nuclear transfer of donor nuclei into recipient oocytes, whose own nuclear DNA
      has been removed, can result in large numbers of identical individuals. Moreover,
      clones can be produced using donor cells from sterile animals, such as steers and
      geldings, and, unlike their genetic source, these clones are fertile. In reality,
      due to low efficiencies and the high costs of cloning domestic species, only a
      limited number of identical individuals are generally produced, and these clones
      are primarily used as breed stock. In addition to providing a means of rescuing
      and propagating valuable genetics, somatic cell nuclear transfer (SCNT) research
      has contributed knowledge that has led to the direct reprogramming of cells
      (e.g., to induce pluripotent stem cells) and a better understanding of epigenetic
      regulation during embryonic development. In this review, I provide a broad
      overview of the historical development of cloning in domestic animals, of its
      application to the propagation of livestock and transgenic animal production, and
      of its scientific promise for advancing basic research. 

PMID- 26195772
TI  - Top-down modulation in the infant brain: Learning-induced expectations rapidly
      affect the sensory cortex at 6 months.
AB  - Recent theoretical work emphasizes the role of expectation in neural processing,
      shifting the focus from feed-forward cortical hierarchies to models that include
      extensive feedback (e.g., predictive coding). Empirical support for expectation
      related feedback is compelling but restricted to adult humans and nonhuman
      animals. Given the considerable differences in neural organization, connectivity,
      and efficiency between infant and adult brains, it is a crucial yet open question
      whether expectation-related feedback is an inherent property of the cortex (i.e.,
      operational early in development) or whether expectation-related feedback
      develops with extensive experience and neural maturation. To determine whether
      infants' expectations about future sensory input modulate their sensory cortices
      without the confounds of stimulus novelty or repetition suppression, we used a
      cross-modal (audiovisual) omission paradigm and used functional near-infrared
      spectroscopy (fNIRS) to record hemodynamic responses in the infant cortex. We
      show that the occipital cortex of 6-month-old infants exhibits the signature of
      expectation-based feedback. Crucially, we found that this region does not respond
      to auditory stimuli if they are not predictive of a visual event. Overall, these
      findings suggest that the young infant's brain is already capable of some
      rudimentary form of expectation-based feedback. 

PMID- 26195773
TI  - Complex dynamics of synergistic coinfections on realistically clustered networks.
AB  - We investigate the impact of contact structure clustering on the dynamics of
      multiple diseases interacting through coinfection of a single individual, two
      problems typically studied independently. We highlight how clustering, which is
      well known to hinder propagation of diseases, can actually speed up epidemic
      propagation in the context of synergistic coinfections if the strength of the
      coupling matches that of the clustering. We also show that such dynamics lead to
      a first-order transition in endemic states, where small changes in
      transmissibility of the diseases can lead to explosive outbreaks and regions
      where these explosive outbreaks can only happen on clustered networks. We develop
      a mean-field model of coinfection of two diseases following susceptible
      infectious-susceptible dynamics, which is allowed to interact on a general class
      of modular networks. We also introduce a criterion based on tertiary infections
      that yields precise analytical estimates of when clustering will lead to faster
      propagation than nonclustered networks. Our results carry importance for
      epidemiology, mathematical modeling, and the propagation of interacting phenomena
      in general. We make a call for more detailed epidemiological data of interacting
      coinfections. 

PMID- 26195774
TI  - Clonal reproduction in fungi.
AB  - Research over the past two decades shows that both recombination and clonality
      are likely to contribute to the reproduction of all fungi. This view of fungi is
      different from the historical and still commonly held view that a large fraction
      of fungi are exclusively clonal and that some fungi have been exclusively clonal
      for hundreds of millions of years. Here, we first will consider how these two
      historical views have changed. Then we will examine the impact on fungal research
      of the concept of restrained recombination [Tibayrenc M, Ayala FJ (2012) Proc
      Natl Acad Sci USA 109 (48):E3305-E3313]. Using animal and human pathogenic fungi,
      we examine extrinsic restraints on recombination associated with bottlenecks in
      genetic variation caused by geographic dispersal and extrinsic restraints caused
      by shifts in reproductive mode associated with either disease transmission or
      hybridization. Using species of the model yeast Saccharomyces and the model
      filamentous fungus Neurospora, we examine intrinsic restraints on recombination
      associated with mating systems that range from strictly clonal at one extreme to
      fully outbreeding at the other and those that lie between, including selfing and
      inbreeding. We also consider the effect of nomenclature on perception of
      reproductive mode and a means of comparing the relative impact of clonality and
      recombination on fungal populations. Last, we consider a recent hypothesis
      suggesting that fungi thought to have the most severe intrinsic constraints on
      recombination actually may have the fewest. 

PMID- 26195775
TI  - Earliest economic exploitation of chicken outside East Asia: Evidence from the
      Hellenistic Southern Levant.
AB  - Chicken (Gallus gallus domesticus) is today one of the most widespread
      domesticated species and is a main source of protein in the human diet. However,
      for thousands of years exploitation of chickens was confined to symbolic and
      social domains such as cockfighting. The question of when and where chickens were
      first used for economic purposes remains unresolved. The results of our faunal
      analysis demonstrate that the Hellenistic (fourth-second centuries B.C.E.) site
      of Maresha, Israel, is the earliest site known today where economic exploitation
      of chickens was widely practiced. We base our claim on the exceptionally high
      frequency of chicken bones at that site, the majority of which belong to adult
      individuals, and on the observed 2:1 ratio of female to male bones. These results
      are supported further by an extensive survey of faunal remains from 234 sites in
      the Southern Levant, spanning more than three millennia, which shows a sharp
      increase in the frequency of chicken during the Hellenistic period. We further
      argue that the earliest secure evidence for economic exploitation of chickens in
      Europe dates to the first century B.C.E. and therefore is predated by the finds
      in the Southern Levant by at least a century. We suggest that the gradual
      acclimatization of chickens in the Southern Levant and its gradual integration
      into the local economy, the latter fully accomplished in the Hellenistic period,
      was a crucial step in the adoption of this species in European husbandry some 100
      y later. 

PMID- 26195776
TI  - The pH low insertion peptide pHLIP Variant 3 as a novel marker of acidic
      malignant lesions.
AB  - Current strategies for early detection of breast and other cancers are limited in
      part because some lesions identified as potentially malignant do not develop into
      aggressive tumors. Acid pH has been suggested as a key characteristic of
      aggressive tumors that might distinguish aggressive lesions from more indolent
      pathology. We therefore investigated the novel class of molecules, pH low
      insertion peptides (pHLIPs), as markers of low pH in tumor allografts and of
      malignant lesions in a mouse model of spontaneous breast cancer, BALB/neu-T.
      pHLIP Variant 3 (Var3) conjugated with fluorescent Alexa546 was shown to insert
      into tumor spheroids in a sequence-specific manner. Its signal reflected pH in
      murine tumors. It was induced by carbonic anhydrase IX (CAIX) overexpression and
      inhibited by acetazolamide (AZA) administration. By using (31)P magnetic
      resonance spectroscopy (MRS), we demonstrated that pHLIP Var3 was retained in
      tumors of pH equal to or less than 6.7 but not in tissues of higher pH. In
      BALB/neu-T mice at different stages of the disease, the fluorescent signal from
      pHLIP Var3 marked cancerous lesions with a very low false-positive rate. However,
      only ~60% of the smallest lesions retained a pHLIP Var3 signal, suggesting
      heterogeneity in pH. Taken together, these results show that pHLIP can identify
      regions of lower pH, allowing for its development as a theranostic tool for
      clinical applications. 

PMID- 26195777
TI  - Clonality and intracellular polyploidy in virus evolution and pathogenesis.
AB  - In the present article we examine clonality in virus evolution. Most viruses
      retain an active recombination machinery as a potential means to initiate new
      levels of genetic exploration that go beyond those attainable solely by point
      mutations. However, despite abundant recombination that may be linked to
      molecular events essential for genome replication, herein we provide evidence
      that generation of recombinants with altered biological properties is not
      essential for the completion of the replication cycles of viruses, and that viral
      lineages (near-clades) can be defined. We distinguish mechanistically active but
      inconsequential recombination from evolutionarily relevant recombination,
      illustrated by episodes in the field and during experimental evolution. In the
      field, recombination has been at the origin of new viral pathogens, and has
      conferred fitness advantages to some viruses once the parental viruses have
      attained a sufficient degree of diversification by point mutations. In the
      laboratory, recombination mediated a salient genome segmentation of foot-and
      mouth disease virus, an important animal pathogen whose genome in nature has
      always been characterized as unsegmented. We propose a model of continuous
      mutation and recombination, with punctuated, biologically relevant recombination
      events for the survival of viruses, both as disease agents and as promoters of
      cellular evolution. Thus, clonality is the standard evolutionary mode for viruses
      because recombination is largely inconsequential, since the decisive events for
      virus replication and survival are not dependent on the exchange of genetic
      material and formation of recombinant (mosaic) genomes. 

PMID- 26195778
TI  - Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii.
AB  - Cancer is a general name for more than 100 malignant diseases. It is postulated
      that all cancers start from a single abnormal cell that grows out of control.
      Untreated cancers can cause serious consequences and deaths. Great progress has
      been made in cancer research that has significantly improved our knowledge and
      understanding of the nature and mechanisms of the disease, but the origins of
      cancer are far from being well understood due to the limitations of suitable
      model systems and to the complexities of the disease. In view of the fact that
      cancers are found in various species of vertebrates and other metazoa, here, we
      suggest that cancer also occurs in parasitic protozoans such as Trypanosoma
      brucei, a blood parasite, and Toxoplasma gondii, an obligate intracellular
      pathogen. Without treatment, these protozoan cancers may cause severe disease and
      death in mammals, including humans. The simpler genomes of these single-cell
      organisms, in combination with their complex life cycles and fascinating life
      cycle differentiation processes, may help us to better understand the origins of
      cancers and, in particular, leukemias. 

PMID- 26195780
TI  - Stanton J. Peale: Deciphering the motions of planets and moons.

PMID- 26195779
TI  - Mitochondrial genomes are retained by selective constraints on protein targeting.
AB  - Mitochondria are energy-producing organelles in eukaryotic cells considered to be
      of bacterial origin. The mitochondrial genome has evolved under selection for
      minimization of gene content, yet it is not known why not all mitochondrial genes
      have been transferred to the nuclear genome. Here, we predict that hydrophobic
      membrane proteins encoded by the mitochondrial genomes would be recognized by the
      signal recognition particle and targeted to the endoplasmic reticulum if they
      were nuclear-encoded and translated in the cytoplasm. Expression of the
      mitochondrially encoded proteins Cytochrome oxidase subunit 1, Apocytochrome b,
      and ATP synthase subunit 6 in the cytoplasm of HeLa cells confirms export to the
      endoplasmic reticulum. To examine the extent to which the mitochondrial proteome
      is driven by selective constraints within the eukaryotic cell, we investigated
      the occurrence of mitochondrial protein domains in bacteria and eukaryotes. The
      accessory protein domains of the oxidative phosphorylation system are unique to
      mitochondria, indicating the evolution of new protein folds. Most of the
      identified domains in the accessory proteins of the ribosome are also found in
      eukaryotic proteins of other functions and locations. Overall, one-third of the
      protein domains identified in mitochondrial proteins are only rarely found in
      bacteria. We conclude that the mitochondrial genome has been maintained to ensure
      the correct localization of highly hydrophobic membrane proteins. Taken together,
      the results suggest that selective constraints on the eukaryotic cell have played
      a major role in modulating the evolution of the mitochondrial genome and
      proteome. 

PMID- 26195781
TI  - Keap1 regulates inflammatory signaling in Mycobacterium avium-infected human
      macrophages.
AB  - Several mechanisms are involved in controlling intracellular survival of
      pathogenic mycobacteria in host macrophages, but how these mechanisms are
      regulated remains poorly understood. We report a role for Kelch-like ECH
      associated protein 1 (Keap1), an oxidative stress sensor, in regulating
      inflammation induced by infection with Mycobacterium avium in human primary
      macrophages. By using confocal microscopy, we found that Keap1 associated with
      mycobacterial phagosomes in a time-dependent manner, whereas siRNA-mediated
      knockdown of Keap1 increased M. avium-induced expression of inflammatory
      cytokines and type I interferons (IFNs). We show evidence of a mechanism whereby
      Keap1, as part of an E3 ubiquitin ligase complex with Cul3 and Rbx1, facilitates
      ubiquitination and degradation of IkappaB kinase (IKK)-beta thus terminating IKK
      activity. Keap1 knockdown led to increased nuclear translocation of transcription
      factors NF-kappaB, IFN regulatory factor (IRF) 1, and IRF5 driving the expression
      of inflammatory cytokines and IFN-beta. Furthermore, knockdown of other members
      of the Cul3 ubiquitin ligase complex also led to increased cytokine expression,
      further implicating this ligase complex in the regulation of the IKK family.
      Finally, increased inflammatory responses in Keap1-silenced cells contributed to
      decreased intracellular growth of M. avium in primary human macrophages that was
      reconstituted with inhibitors of IKKbeta or TANK-binding kinase 1 (TBK1). Taken
      together, we propose that Keap1 acts as a negative regulator for the control of
      inflammatory signaling in M. avium-infected human primary macrophages. Although
      this might be important to avoid sustained or overwhelming inflammation, our data
      suggest that a negative consequence could be facilitated growth of pathogens like
      M. avium inside macrophages. 

PMID- 26195782
TI  - Robust network oscillations during mammalian respiratory rhythm generation driven
      by synaptic dynamics.
AB  - How might synaptic dynamics generate synchronous oscillations in neuronal
      networks? We address this question in the preBotzinger complex (preBotC), a
      brainstem neural network that paces robust, yet labile, inspiration in mammals.
      The preBotC is composed of a few hundred neurons that alternate bursting activity
      with silent periods, but the mechanism underlying this vital rhythm remains
      elusive. Using a computational approach to model a randomly connected neuronal
      network that relies on short-term synaptic facilitation (SF) and depression (SD),
      we show that synaptic fluctuations can initiate population activities through
      recurrent excitation. We also show that a two-step SD process allows activity in
      the network to synchronize (bursts) and generate a population refractory period
      (silence). The model was validated against an array of experimental conditions,
      which recapitulate several processes the preBotC may experience. Consistent with
      the modeling assumptions, we reveal, by electrophysiological recordings, that
      SF/SD can occur at preBotC synapses on timescales that influence rhythmic
      population activity. We conclude that nondeterministic neuronal spiking and
      dynamic synaptic strengths in a randomly connected network are sufficient to give
      rise to regular respiratory-like rhythmic network activity and lability, which
      may play an important role in generating the rhythm for breathing and other
      coordinated motor activities in mammals. 

PMID- 26195783
TI  - Regulation of ribosomal DNA amplification by the TOR pathway.
AB  - Repeated regions are widespread in eukaryotic genomes, and key functional
      elements such as the ribosomal DNA tend to be formed of high copy repeated
      sequences organized in tandem arrays. In general, high copy repeats are
      remarkably stable, but a number of organisms display rapid ribosomal DNA
      amplification at specific times or under specific conditions. Here we demonstrate
      that target of rapamycin (TOR) signaling stimulates ribosomal DNA amplification
      in budding yeast, linking external nutrient availability to ribosomal DNA copy
      number. We show that ribosomal DNA amplification is regulated by three histone
      deacetylases: Sir2, Hst3, and Hst4. These enzymes control homologous
      recombination-dependent and nonhomologous recombination-dependent amplification
      pathways that act in concert to mediate rapid, directional ribosomal DNA copy
      number change. Amplification is completely repressed by rapamycin, an inhibitor
      of the nutrient-responsive TOR pathway; this effect is separable from growth rate
      and is mediated directly through Sir2, Hst3, and Hst4. Caloric restriction is
      known to up-regulate expression of nicotinamidase Pnc1, an enzyme that enhances
      Sir2, Hst3, and Hst4 activity. In contrast, normal glucose concentrations stretch
      the ribosome synthesis capacity of cells with low ribosomal DNA copy number, and
      we find that these cells show a previously unrecognized transcriptional response
      to caloric excess by reducing PNC1 expression. PNC1 down-regulation forms a key
      element in the control of ribosomal DNA amplification as overexpression of PNC1
      substantially reduces ribosomal DNA amplification rate. Our results reveal how a
      signaling pathway can orchestrate specific genome changes and demonstrate that
      the copy number of repetitive DNA can be altered to suit environmental
      conditions. 

PMID- 26195784
TI  - Hole hopping through tyrosine/tryptophan chains protects proteins from oxidative
      damage.
AB  - Living organisms have adapted to atmospheric dioxygen by exploiting its oxidizing
      power while protecting themselves against toxic side effects. Reactive oxygen and
      nitrogen species formed during oxidative stress, as well as high-potential
      reactive intermediates formed during enzymatic catalysis, could rapidly and
      irreversibly damage polypeptides were protective mechanisms not available. Chains
      of redox-active tyrosine and tryptophan residues can transport potentially
      damaging oxidizing equivalents (holes) away from fragile active sites and toward
      protein surfaces where they can be scavenged by cellular reductants. Precise
      positioning of these chains is required to provide effective protection without
      inhibiting normal function. A search of the structural database reveals that
      about one third of all proteins contain Tyr/Trp chains composed of three or more
      residues. Although these chains are distributed among all enzyme classes, they
      appear with greatest frequency in the oxidoreductases and hydrolases. Consistent
      with a redox-protective role, approximately half of the dioxygen-using
      oxidoreductases have Tyr/Trp chain lengths >=3 residues. Among the hydrolases,
      long Tyr/Trp chains appear almost exclusively in the glycoside hydrolases. These
      chains likely are important for substrate binding and positioning, but a
      secondary redox role also is a possibility. 

PMID- 26195785
TI  - Simple mechanism whereby the F1-ATPase motor rotates with near-perfect
      chemomechanical energy conversion.
AB  - F1-ATPase is a motor enzyme in which a central shaft gamma subunit rotates 120
      degrees  per ATP in the cylinder made of alpha3beta3 subunits. During rotation,
      the chemical energy of ATP hydrolysis (DeltaGATP) is converted almost entirely
      into mechanical work by an elusive mechanism. We measured the force for rotation
      (torque) under various DeltaGATP conditions as a function of rotation angles of
      the gamma subunit with quasi-static, single-molecule manipulation and estimated
      mechanical work (torque * traveled angle) from the area of the function. The
      torque functions show three sawtooth-like repeats of a steep jump and linear
      descent in one catalytic turnover, indicating a simple physical model in which
      the motor is driven by three springs aligned along a 120 degrees  rotation angle.
      Although the second spring is unaffected by DeltaGATP, activation of the first
      spring (timing of the torque jump) delays at low [ATP] (or high [ADP]) and
      activation of the third spring delays at high [Pi]. These shifts decrease the
      size and area of the sawtooth (magnitude of the work). Thus, F1-ATPase responds
      to the change of DeltaGATP by shifting the torque jump timing and uses DeltaGATP
      for the mechanical work with near-perfect efficiency. 

PMID- 26195786
TI  - Conformational propensities of intrinsically disordered proteins influence the
      mechanism of binding and folding.
AB  - Intrinsically disordered proteins (IDPs) frequently function in protein
      interaction networks that regulate crucial cellular signaling pathways. Many IDPs
      undergo transitions from disordered conformational ensembles to folded structures
      upon binding to their cellular targets. Several possible binding mechanisms for
      coupled folding and binding have been identified: folding of the IDP after
      association with the target ("induced fit"), or binding of a prefolded state in
      the conformational ensemble of the IDP to the target protein ("conformational
      selection"), or some combination of these two extremes. The interaction of the
      intrinsically disordered phosphorylated kinase-inducible domain (pKID) of the
      cAMP-response element binding (CREB) protein with the KIX domain of a general
      transcriptional coactivator CREB-binding protein (CBP) provides an example of the
      induced-fit mechanism. Here we show by NMR relaxation dispersion experiments that
      a different intrinsically disordered ligand, the transactivation domain of the
      transcription factor c-Myb, interacts with KIX at the same site as pKID but via a
      different binding mechanism that involves elements of conformational selection
      and induced fit. In contrast to pKID, the c-Myb activation domain has a strong
      propensity for spontaneous helix formation in its N-terminal region, which binds
      to KIX in a predominantly folded conformation. The C-terminal region of c-Myb
      exhibits a much smaller helical propensity and likely folds via an induced-fit
      process after binding to KIX. We propose that the intrinsic secondary structure
      propensities of pKID and c-Myb determine their binding mechanisms, consistent
      with their functions as inducible and constitutive transcriptional activators. 

PMID- 26195787
TI  - Ubl4A is required for insulin-induced Akt plasma membrane translocation through
      promotion of Arp2/3-dependent actin branching.
AB  - The serine-threonine kinase Akt is a key regulator of cell proliferation and
      survival, glucose metabolism, cell mobility, and tumorigenesis. Activation of Akt
      by extracellular stimuli such as insulin centers on the interaction of Akt with
      PIP3 on the plasma membrane, where it is subsequently phosphorylated and
      activated by upstream protein kinases. However, it is not known how Akt is
      recruited to the plasma membrane upon stimulation. Here we report that ubiquitin
      like protein 4A (Ubl4A) plays a crucial role in insulin-induced Akt plasma
      membrane translocation. Ubl4A knockout newborn mice have defective Akt-dependent
      glycogen synthesis and increased neonatal mortality. Loss of Ubl4A results in the
      impairment of insulin-induced Akt translocation to the plasma membrane and
      activation. Akt binds actin-filaments and colocalizes with actin-related protein
      2 and 3 (Arp2/3) complex in the membrane ruffles and lamellipodia. Ubl4A directly
      interacts with Arp2/3 to accelerate actin branching and networking, allowing Akt
      to be in close proximity to the plasma membrane for activation upon insulin
      stimulation. Our finding reveals a new mechanism by which Akt is recruited to the
      plasma membrane for activation, thereby providing a missing link in Akt
      signaling. 

PMID- 26195788
TI  - CBR antimicrobials inhibit RNA polymerase via at least two bridge-helix cap
      mediated effects on nucleotide addition.
AB  - RNA polymerase inhibitors like the CBR class that target the enzyme's complex
      catalytic center are attractive leads for new antimicrobials. Catalysis by RNA
      polymerase involves multiple rearrangements of bridge helix, trigger loop, and
      active-center side chains that isomerize the triphosphate of bound NTP and two
      Mg(2+) ions from a preinsertion state to a reactive configuration. CBR inhibitors
      target a crevice between the N-terminal portion of the bridge helix and a
      surrounding cap region within which the bridge helix is thought to rearrange
      during the nucleotide addition cycle. We report crystal structures of CBR
      inhibitor/Escherichia coli RNA polymerase complexes as well as biochemical tests
      that establish two distinct effects of the inhibitors on the RNA polymerase
      catalytic site. One effect involves inhibition of trigger-loop folding via the F
      loop in the cap, which affects both nucleotide addition and hydrolysis of 3'
      terminal dinucleotides in certain backtracked complexes. The second effect is
      trigger-loop independent, affects only nucleotide addition and
      pyrophosphorolysis, and may involve inhibition of bridge-helix movements that
      facilitate reactive triphosphate alignment. 

PMID- 26195789
TI  - Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU:
      Solution structure of a peptide-quadruplex complex.
AB  - Four-stranded nucleic acid structures called G-quadruplexes have been associated
      with important cellular processes, which should require G-quadruplex-protein
      interaction. However, the structural basis for specific G-quadruplex recognition
      by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase
      associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically
      binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18
      amino acid G-quadruplex-binding domain of RHAU and determined the structure of
      this peptide bound to a parallel DNA G-quadruplex. Our structure explains how
      RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a
      terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three
      anchor-point electrostatic interactions between three positively charged amino
      acids and negatively charged phosphate groups. This binding mode is strikingly
      similar to that of most ligands selected for specific G-quadruplex targeting.
      Binding to an exposed G-tetrad represents a simple and efficient way to
      specifically target G-quadruplex structures. 

PMID- 26195790
TI  - The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry
      and suggests a hit-and-run mechanism in mouse cells.
AB  - X-chromosome inactivation (XCI) is initiated by the long noncoding RNA Xist,
      which coats the inactive X (Xi) and targets Polycomb repressive complex 2 (PRC2)
      in cis. Epigenomic analyses have provided significant insight into Xist binding
      patterns and chromatin organization of the Xi. However, such epigenomic analyses
      are limited by averaging of population-wide dynamics and do not inform behavior
      of single cells. Here we view Xist RNA and the Xi at 20-nm resolution using
      STochastic Optical Reconstruction Microscopy (STORM) in mouse cells. We observe
      dynamics at the single-cell level not predicted by epigenomic analysis. Only ~50
      hubs of Xist RNA occur on the Xi in the maintenance phase, corresponding to 50
      100 Xist molecules per Xi and contrasting with the chromosome-wide "coat"
      observed by deep sequencing and conventional microscopy. Likewise, only ~50 hubs
      PRC2 are observed. PRC2 and Xist foci are not randomly distributed but showed
      statistically significant spatial association. Knock-off experiments enable
      visualization of the dynamics of dissociation and relocalization onto the Xi and
      support a functional tethering of Xist and PRC2. Our analysis reveals that Xist
      PRC2 complexes are less numerous than expected and suggests methylation of
      nucleosomes in a hit-and-run model. 

PMID- 26195791
TI  - Manipulating electronic phase separation in strongly correlated oxides with an
      ordered array of antidots.
AB  - The interesting transport and magnetic properties in manganites depend
      sensitively on the nucleation and growth of electronic phase-separated domains.
      By fabricating antidot arrays in La0.325Pr0.3Ca0.375MnO3 (LPCMO) epitaxial thin
      films, we create ordered arrays of micrometer-sized ferromagnetic metallic (FMM)
      rings in the LPCMO films that lead to dramatically increased metal-insulator
      transition temperatures and reduced resistances. The FMM rings emerge from the
      edges of the antidots where the lattice symmetry is broken. Based on our Monte
      Carlo simulation, these FMM rings assist the nucleation and growth of FMM phase
      domains increasing the metal-insulator transition with decreasing temperature or
      increasing magnetic field. This study points to a way in which electronic phase
      separation in manganites can be artificially controlled without changing chemical
      composition or applying external field. 

PMID- 26195793
TI  - Enhanced enstrophy generation for turbulent convection in low-Prandtl-number
      fluids.
AB  - Turbulent convection is often present in liquids with a kinematic viscosity much
      smaller than the diffusivity of the temperature. Here we reveal why these
      convection flows obey a much stronger level of fluid turbulence than those in
      which kinematic viscosity and thermal diffusivity are the same; i.e., the Prandtl
      number Pr is unity. We compare turbulent convection in air at Pr=0.7 and in
      liquid mercury at Pr=0.021. In this comparison the Prandtl number at constant
      Grashof number Gr is varied, rather than at constant Rayleigh number Ra as
      usually done. Our simulations demonstrate that the turbulent Kolmogorov-like
      cascade is extended both at the large- and small-scale ends with decreasing Pr.
      The kinetic energy injection into the flow takes place over the whole cascade
      range. In contrast to convection in air, the kinetic energy injection rate is
      particularly enhanced for liquid mercury for all scales larger than the
      characteristic width of thermal plumes. As a consequence, mean values and
      fluctuations of the local strain rates are increased, which in turn results in
      significantly enhanced enstrophy production by vortex stretching. The normalized
      distributions of enstrophy production in the bulk and the ratio of the principal
      strain rates are found to agree for both Prs. Despite the different energy
      injection mechanisms, the principal strain rates also agree with those in
      homogeneous isotropic turbulence conducted at the same Reynolds numbers as for
      the convection flows. Our results have thus interesting implications for small
      scale turbulence modeling of liquid metal convection in astrophysical and
      technological applications.

PMID- 26195792
TI  - Knockout silkworms reveal a dispensable role for juvenile hormones in
      holometabolous life cycle.
AB  - Insect juvenile hormones (JHs) prevent precocious metamorphosis and allow larvae
      to undergo multiple rounds of status quo molts. However, the roles of JHs during
      the embryonic and very early larval stages have not been fully understood. We
      generated and characterized knockout silkworms (Bombyx mori) with null mutations
      in JH biosynthesis or JH receptor genes using genome-editing tools. We found that
      embryonic growth and morphogenesis are largely independent of JHs in Bombyx and
      that, even in the absence of JHs or JH signaling, pupal characters are not formed
      in first- or second-instar larvae, and precocious metamorphosis is induced after
      the second instar at the earliest. We also show by mosaic analysis that a pupal
      specifier gene broad, which is dramatically up-regulated in the late stage of the
      last larval instar, is essential for pupal commitment in the epidermis.
      Importantly, the mRNA expression level of broad, which is thought to be repressed
      by JHs, remained at very low basal levels during the early larval instars of JH
      deficient or JH signaling-deficient knockouts. Therefore, our study suggests that
      the long-accepted paradigm that JHs maintain the juvenile status throughout
      larval life should be revised because the larval status can be maintained by a JH
      independent mechanism in very early larval instars. We propose that the lack of
      competence for metamorphosis during the early larval stages may result from the
      absence of an unidentified broad-inducing factor, i.e., a competence factor. 

PMID- 26195794
TI  - Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of
      CEACAM20 in the intestinal epithelium.
AB  - Intestinal epithelial cells contribute to regulation of intestinal immunity in
      mammals, but the detailed molecular mechanisms of such regulation have remained
      largely unknown. Stomach-cancer-associated protein tyrosine phosphatase 1 (SAP-1,
      also known as PTPRH) is a receptor-type protein tyrosine phosphatase that is
      localized specifically at microvilli of the brush border in gastrointestinal
      epithelial cells. Here we show that SAP-1 ablation in interleukin (IL)-10
      deficient mice, a model of inflammatory bowel disease, resulted in a marked
      increase in the severity of colitis in association with up-regulation of mRNAs
      for various cytokines and chemokines in the colon. Tyrosine phosphorylation of
      carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an
      intestinal microvillus-specific transmembrane protein of the Ig superfamily, was
      greatly increased in the intestinal epithelium of the SAP-1-deficient animals,
      suggesting that this protein is a substrate for SAP-1. Tyrosine phosphorylation
      of CEACAM20 by the protein tyrosine kinase c-Src and the consequent association
      of CEACAM20 with spleen tyrosine kinase (Syk) promoted the production of IL-8 in
      cultured cells through the activation of nuclear factor-kappaB (NF-kappaB). In
      addition, SAP-1 and CEACAM20 were found to form a complex through interaction of
      their ectodomains. SAP-1 and CEACAM20 thus constitute a regulatory system through
      which the intestinal epithelium contributes to intestinal immunity. 

PMID- 26195795
TI  - Burst pacemaker activity of the sinoatrial node in sodium-calcium exchanger
      knockout mice.
AB  - In sinoatrial node (SAN) cells, electrogenic sodium-calcium exchange (NCX) is the
      dominant calcium (Ca) efflux mechanism. However, the role of NCX in the
      generation of SAN automaticity is controversial. To investigate the contribution
      of NCX to pacemaking in the SAN, we performed optical voltage mapping and high
      speed 2D laser scanning confocal microscopy (LSCM) of Ca dynamics in an ex vivo
      intact SAN/atrial tissue preparation from atrial-specific NCX knockout (KO) mice.
      These mice lack P waves on electrocardiograms, and isolated NCX KO SAN cells are
      quiescent. Voltage mapping revealed disorganized and arrhythmic depolarizations
      within the NCX KO SAN that failed to propagate into the atria. LSCM revealed
      intermittent bursts of Ca transients. Bursts were accompanied by rising diastolic
      Ca, culminating in long pauses dominated by Ca waves. The L-type Ca channel
      agonist BayK8644 reduced the rate of Ca transients and inhibited burst generation
      in the NCX KO SAN whereas the Ca buffer 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid (acetoxymethyl ester) (BAPTA AM) did the opposite. These results
      suggest that cellular Ca accumulation hinders spontaneous depolarization in the
      NCX KO SAN, possibly by inhibiting L-type Ca currents. The funny current (If)
      blocker ivabradine also suppressed NCX KO SAN automaticity. We conclude that
      pacemaker activity is present in the NCX KO SAN, generated by a mechanism that
      depends upon If. However, the absence of NCX-mediated depolarization in
      combination with impaired Ca efflux results in intermittent bursts of pacemaker
      activity, reminiscent of human sinus node dysfunction and "tachy-brady" syndrome.

PMID- 26195797
TI  - Accuracy of initial codon selection by aminoacyl-tRNAs on the mRNA-programmed
      bacterial ribosome.
AB  - We used a cell-free system with pure Escherichia coli components to study initial
      codon selection of aminoacyl-tRNAs in ternary complex with elongation factor Tu
      and GTP on messenger RNA-programmed ribosomes. We took advantage of the universal
      rate-accuracy trade-off for all enzymatic selections to determine how the
      efficiency of initial codon readings decreased linearly toward zero as the
      accuracy of discrimination against near-cognate and wobble codon readings
      increased toward the maximal asymptote, the d value. We report data on the rate
      accuracy variation for 7 cognate, 7 wobble, and 56 near-cognate codon readings
      comprising about 15% of the genetic code. Their d values varied about 400-fold in
      the 200-80,000 range depending on type of mismatch, mismatch position in the
      codon, and tRNA isoacceptor type. We identified error hot spots (d = 200) for U:G
      misreading in second and U:U or G:A misreading in third codon position by His
      tRNA(His) and, as also seen in vivo, Glu-tRNA(Glu). We suggest that the
      proofreading mechanism has evolved to attenuate error hot spots in initial
      selection such as those found here. 

PMID- 26195796
TI  - Huntington's disease: Neural dysfunction linked to inositol polyphosphate
      multikinase.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disease caused by a
      glutamine repeat expansion in mutant huntingtin (mHtt). Despite the known genetic
      cause of HD, the pathophysiology of this disease remains to be elucidated.
      Inositol polyphosphate multikinase (IPMK) is an enzyme that displays soluble
      inositol phosphate kinase activity, lipid kinase activity, and various
      noncatalytic interactions. We report a severe loss of IPMK in the striatum of HD
      patients and in several cellular and animal models of the disease. This depletion
      reflects mHtt-induced impairment of COUP-TF-interacting protein 2 (Ctip2), a
      striatal-enriched transcription factor for IPMK, as well as alterations in IPMK
      protein stability. IPMK overexpression reverses the metabolic activity deficit in
      a cell model of HD. IPMK depletion appears to mediate neural dysfunction, because
      intrastriatal delivery of IPMK abates the progression of motor abnormalities and
      rescues striatal pathology in transgenic murine models of HD. 

PMID- 26195799
TI  - Binary nanoparticle superlattices of soft-particle systems.
AB  - The solid-phase diagram of binary systems consisting of particles of diameter
      sigmaA = sigma and sigmaB = gammasigma (gamma <= 1) interacting with an inverse p
      = 12 power law is investigated as a paradigm of a soft potential. In addition to
      the diameter ratio gamma that characterizes hard-sphere models, the phase diagram
      is a function of an additional parameter that controls the relative interaction
      strength between the different particle types. Phase diagrams are determined from
      extremes of thermodynamic functions by considering 15 candidate lattices. In
      general, it is shown that the phase diagram of a soft repulsive potential leads
      to the morphological diversity observed in experiments with binary nanoparticles,
      thus providing a general framework to understand their phase diagrams. Particular
      emphasis is given to the two most successful crystallization strategies so far:
      evaporation of solvent from nanoparticles with grafted hydrocarbon ligands and
      DNA programmable self-assembly.

PMID- 26195798
TI  - Structural elements that underlie Doc2beta function during asynchronous synaptic
      transmission.
AB  - Double C2-like domain-containing proteins alpha and beta (Doc2alpha and Doc2beta)
      are tandem C2-domain proteins proposed to function as Ca(2+) sensors for
      asynchronous neurotransmitter release. Here, we systematically analyze each of
      the negatively charged residues that mediate binding of Ca(2+) to the beta
      isoform. The Ca(2+) ligands in the C2A domain were dispensable for Ca(2+)
      dependent translocation to the plasma membrane, with one exception:
      neutralization of D220 resulted in constitutive translocation. In contrast, three
      of the five Ca(2+) ligands in the C2B domain are required for translocation.
      Importantly, translocation was correlated with the ability of the mutants to
      enhance asynchronous release when overexpressed in neurons. Finally, replacement
      of specific Ca(2+)/lipid-binding loops of synaptotagmin 1, a Ca(2+) sensor for
      synchronous release, with corresponding loops from Doc2beta, resulted in chimeras
      that yielded slower kinetics in vitro and slower excitatory postsynaptic current
      decays in neurons. Together, these data reveal the key determinants of Doc2beta
      that underlie its function during the slow phase of synaptic transmission. 

PMID- 26195800
TI  - Entner-Doudoroff pathway for sulfoquinovose degradation in Pseudomonas putida
      SQ1.
AB  - Sulfoquinovose (SQ; 6-deoxy-6-sulfoglucose) is the polar head group of the plant
      sulfolipid SQ-diacylglycerol, and SQ comprises a major proportion of the
      organosulfur in nature, where it is degraded by bacteria. A first degradation
      pathway for SQ has been demonstrated recently, a "sulfoglycolytic" pathway, in
      addition to the classical glycolytic (Embden-Meyerhof) pathway in Escherichia
      coli K-12; half of the carbon of SQ is abstracted as dihydroxyacetonephosphate
      (DHAP) and used for growth, whereas a C3-organosulfonate, 2,3-dihydroxypropane
      sulfonate (DHPS), is excreted. The environmental isolate Pseudomonas putida SQ1
      is also able to use SQ for growth, and excretes a different C3-organosulfonate, 3
      sulfolactate (SL). In this study, we revealed the catabolic pathway for SQ in P.
      putida SQ1 through differential proteomics and transcriptional analyses, by in
      vitro reconstitution of the complete pathway by five heterologously produced
      enzymes, and by identification of all four organosulfonate intermediates. The
      pathway follows a reaction sequence analogous to the Entner-Doudoroff pathway for
      glucose-6-phosphate: It involves an NAD(+)-dependent SQ dehydrogenase, 6-deoxy-6
      sulfogluconolactone (SGL) lactonase, 6-deoxy-6-sulfogluconate (SG) dehydratase,
      and 2-keto-3,6-dideoxy-6-sulfogluconate (KDSG) aldolase. The aldolase reaction
      yields pyruvate, which supports growth of P. putida, and 3-sulfolactaldehyde
      (SLA), which is oxidized to SL by an NAD(P)(+)-dependent SLA dehydrogenase. All
      five enzymes are encoded in a single gene cluster that includes, for example,
      genes for transport and regulation. Homologous gene clusters were found in
      genomes of other P. putida strains, in other gamma-Proteobacteria, and in beta-
      and alpha-Proteobacteria, for example, in genomes of Enterobacteria, Vibrio, and
      Halomonas species, and in typical soil bacteria, such as Burkholderia,
      Herbaspirillum, and Rhizobium. 

PMID- 26195801
TI  - IL-15 receptor alpha signaling constrains the development of IL-17-producing
      gammadelta T cells.
AB  - The development and homeostasis of gammadelta T cells is highly dependent on
      distinct cytokine networks. Here we examine the role of IL-15 and its unique
      receptor, IL-15Ralpha, in the development of IL-17-producing gammadelta
      (gammadelta-17) T cells. Phenotypic analysis has shown that CD44(high) gammadelta
      17 cells express IL-15Ralpha and the common gamma chain (CD132), yet lack the IL
      2/15Rbeta chain (CD122). Surprisingly, we found an enlarged population of
      gammadelta-17 cells in the peripheral and mesenteric lymph nodes of adult IL
      15Ralpha KO mice, but not of IL-15 KO mice. The generation of mixed chimeras from
      neonatal thymocytes indicated that cell-intrinsic IL-15Ralpha expression was
      required to limit IL-17 production by gammadelta T cells. gammadelta-17 cells
      also were increased in the peripheral lymph nodes of transgenic knock-in mice,
      where the IL-15Ralpha intracellular signaling domain was replaced with the
      intracellular portion of the IL-2Ralpha chain (that lacks signaling capacity).
      Finally, an analysis of neonatal thymi revealed that the CD44(lo/int) precursors
      of gammadelta-17 cells, which also expressed IL-15Ralpha, were increased in
      newborn mice deficient in IL-15Ralpha signaling, but not in IL-15 itself. Thus,
      these findings demonstrate that signaling through IL-15Ralpha regulates the
      development of gammadelta-17 cells early in ontogeny, with long-term effects on
      their peripheral homeostasis in the adult. 

PMID- 26195802
TI  - Spontaneous retrotransposon insertion into TNF 3'UTR causes heart valve disease
      and chronic polyarthritis.
AB  - Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic
      inflammatory diseases that together affect 2-3% of the population. RA and AS
      predominantly involve joints, but heart disease is also a common feature in RA
      and AS patients. Here we have studied a new spontaneous mutation that causes
      severe polyarthritis in bone phenotype spontaneous mutation 1 (BPSM1) mice. In
      addition to joint destruction, mutant mice also develop aortic root aneurism and
      aorto-mitral valve disease that can be fatal depending on the genetic background.
      The cause of the disease is the spontaneous insertion of a retrotransposon into
      the 3' untranslated region (3'UTR) of the tumor necrosis factor (TNF), which
      triggers its strong overexpression in myeloid cells. We found that several
      members of a family of RNA-binding, CCCH-containing zinc-finger proteins control
      TNF expression through its 3'UTR, and we identified a previously unidentified
      regulatory element in the UTR. The disease in BPSM1 mice is independent of the
      adaptive immune system and does not appear to involve inflammatory cytokines
      other than TNF. To our knowledge, this is the first animal model showing both
      polyarthritis and heart disease as a direct result of TNF deregulation. These
      results emphasize the therapeutic potential of anti-TNF drugs for the treatment
      of heart valve disease and identify potential therapeutic targets to control TNF
      expression and inflammation. 

PMID- 26195804
TI  - Effect of dexamethasone in feed on intestinal permeability, differential white
      blood cell counts, and immune organs in broiler chicks.
AB  - We have previously shown that intestinal barrier function can be adversely
      affected by poorly digested diets or feed restriction, resulting in increased
      intestinal inflammation-associated permeability. Three experiments were conducted
      in broilers to evaluate the effect of dexamethasone (DEX) treatment on systemic
      fluorescein isothiocyanate-dextran (FITC-D; 3-5 kDa) levels, indicative of
      increased gut epithelial leakage. Experiment 1 compared DEX injections of 1
      mg/kg, once per day on d 3, 5, and 9, with feed administration at 0.57, 1.7, or
      5.1 ppm d 4 to 10, with FITC-D serum concentrations 2.5 h after gavage with 4.16
      mg/kg FITC-D. All DEX treatments resulted in marked (2 to 6X; P<0.05) increased
      serum FITC-D levels. Feed DEX administration resulted in greater (P<0.05) gut
      permeability than injection at any dose, with numerically optimal effects at the
      lowest dose tested. In experiments 2 and 3, chicks were randomly assigned to a
      starter ration containing either control (CON) or DEX treated feed (0.57 ppm/kg;
      d 3 to 10 experiment 2, d 4 to 10 experiment 3). At d 10, all chicks were treated
      by oral gavage with FITC-D and serum samples were obtained as described above.
      Samples of the liver were aseptically collected, homogenized, diluted 1:4 wt/vol
      in sterile saline, and serial dilutions were plated on tryptic soy agar to
      evaluate total numbers of aerobic bacteria in the liver as an index of bacterial
      translocation (BT). In both experiments, FITC-D absorption was significantly
      enhanced (P<0.05) in DEX-treated chicks, again indicating increased paracellular
      leakage across the gut epithelium associated with dissolution of tight junctions.
      Experiment 2 differential cell counts showed an increased heterophil/lymphocyte
      ratio, and immune organ (spleen and bursa of Fabricius) weights for experiments 2
      and 3 were decreased (P<0.05) from controls. In experiments 2 and 3, dietary DEX
      administration resulted in numerically (experiment 2) or significantly (P<0.05)
      increased enteric BT to the liver, supporting the observation that dietary DEX
      causes a stress-like inflammatory GI response, which may contribute to
      subclinical or clinical disease, and may be a useful model for ongoing disease
      mitigation research related to stress-related diseases of GIT origin.

PMID- 26195805
TI  - Effect of different levels of calcium and phosphorus and their interaction on the
      performance of young broilers.
AB  - A study was conducted to evaluate the interaction among 3 levels of Ca and 4
      levels of nonphytate phosphorus (NPP) on broiler performance, bone ash, and whole
      body fractional retention of Ca and P. Ross male broiler-chicks (n=420) were
      sorted by BW at d 1 posthatch and assigned to 5 cages/diet with 7 birds/cage.
      Twelve diets were arranged in a 3*4 factorial of 3 levels Ca (at 0.5, 0.7, or
      0.9%) and 4 levels NPP (at 0.25, 0.31, 0.38, or 0.45%) with a high dose of
      phytase (1,150 U/kg) in all diets. On d 14, chickens were euthanized and the
      right tibia was collected from 3 birds/replicate; the rest of the animals were
      used to measure whole-body Ca and P retention. An interaction was observed
      between the level of Ca and NPP on feed intake (FI), tibia weight, and bone-ash
      content (P<0.05). Increasing the level of NPP from 0.25 to 0.38% increased FI
      (P<0.05) on chickens fed the high-Ca diet (0.9%), but not with Ca at 0.5 or 0.7%.
      Broilers achieved their greatest weight gain (WG) and bone formation with 0.7% Ca
      and 0.38% NPP. Increasing the dietary Ca decreased its fractional retention from
      74% with dietary Ca at 0.5 to 46% with Ca at 0.9%. The increase in the levels of
      dietary P steadily increased the fractional retention of Ca from 53 to 61%, and
      increased the whole-body Ca content (g/kg BW). It can be concluded that a dietary
      level of 0.38% NPP/kg in diets containing a high dose of phytase (1,150 U/kg) and
      0.7% Ca are adequate to ensure broiler performance and bone ash of broilers from
      d 0 to d 14 posthatch.

PMID- 26195803
TI  - Activity-dependent mismatch between axo-axonic synapses and the axon initial
      segment controls neuronal output.
AB  - The axon initial segment (AIS) is a structure at the start of the axon with a
      high density of sodium and potassium channels that defines the site of action
      potential generation. It has recently been shown that this structure is plastic
      and can change its position along the axon, as well as its length, in a
      homeostatic manner. Chronic activity-deprivation paradigms in a chick auditory
      nucleus lead to a lengthening of the AIS and an increase in neuronal
      excitability. On the other hand, a long-term increase in activity in dissociated
      rat hippocampal neurons results in an outward movement of the AIS and a decrease
      in the cell's excitability. Here, we investigated whether the AIS is capable of
      undergoing structural plasticity in rat hippocampal organotypic slices, which
      retain the diversity of neuronal cell types present at postnatal ages, including
      chandelier cells. These interneurons exclusively target the AIS of pyramidal
      neurons and form rows of presynaptic boutons along them. Stimulating individual
      CA1 pyramidal neurons that express channelrhodopsin-2 for 48 h leads to an
      outward shift of the AIS. Intriguingly, both the pre- and postsynaptic components
      of the axo-axonic synapses did not change position after AIS relocation. We used
      computational modeling to explore the functional consequences of this partial
      mismatch and found that it allows the GABAergic synapses to strongly oppose
      action potential generation, and thus downregulate pyramidal cell excitability.
      We propose that this spatial arrangement is the optimal configuration for a
      homeostatic response to long-term stimulation. 

PMID- 26195806
TI  - Laying hen movement in a commercial aviary: Enclosure to floor and back again.
AB  - Many producers in the laying hen industry, including in North America, are
      phasing out conventional cages in response to consumer demands and sometimes
      subsequent legislation. Alternative housing systems such as aviaries are being
      implemented in an attempt to improve hen welfare. Aviaries provide additional
      space and resources to groups of hens, including a litter area on the floor.
      However, little is known about hen movement between tiered enclosures and floor
      litter areas in aviary systems. Diurnal rhythms and social attraction may result
      in peak times of movement that could lead to overcrowding of areas, or
      alternatively hen preferences may lead to some areas not being fully utilized. We
      monitored hen movement between tiered enclosures and litter areas, including
      movement on and off the outer perch, across the day at peak, mid and end of lay
      in a commercial aviary. Hens moved onto and off of the open litter area across
      the day, transitioning between tiered enclosures, outer perches, open litter
      areas, and litter areas under tiered enclosures. At certain times of day, there
      were periods of greater hen movement down to the open litter area and between
      litter areas. For example, more hens were typically observed exiting enclosures,
      jumping from perches to open litter, and traveling between open litter and litter
      under tiered enclosures in the morning (all P <= 0.001). In all but one instance,
      more hens were observed on open litter areas in the afternoon than at other times
      of day (all P <= 0.029). However, hen re-entry to tiered enclosures showed less
      circadian patterning. Hen movement was observed between areas of interest at all
      sampled time periods, indicating hens use all areas of the system. Further
      research should examine whether all individual hens do move between areas
      equally, including within levels of the tiered enclosure, or if crowding occurs
      on the outer perches or in the litter during times of peak movement. 

PMID- 26195807
TI  - Fear responses and postmortem muscle characteristics of turkeys of two genetic
      lines.
AB  - Commercial turkey production has increased greatly in recent decades. Along with
      increased production, problems with turkey meat quality have also increased.
      Research with other species has demonstrated that differences in meat quality
      exist among pigs and cattle differing in characteristics such as fearfulness.
      However, associations between fear responses and postmortem (PM) muscle
      characteristics related to the meat quality of turkeys have not been examined.
      This study evaluated the test-retest repeatability of responses of male
      commercial (COMM) and randombred (RB) turkeys in an open field (OF) test, which
      is used to assess fear and activity levels of poultry. Another objective of this
      study was to evaluate the relationship between behavioral OF responses and PM
      breast muscle characteristics (pH and R-value) that are related to meat quality.
      Thirdly, this study evaluated differences in pH and R-value between the turkey
      lines. Male COMM and RB turkeys were each housed in groups in 4 pens. Turkeys
      were individually tested in an OF (2.74*2.74 m, divided into 81 squares) at 1, 4,
      and 11 wk (COMM N=27; RB N=33). Turkeys were then grouped into clusters based on
      a cluster analysis of OF behavior. Turkeys were processed and meat quality
      characteristics were evaluated at 15-17 wk for COMM and 20-21 wk for RB turkeys.
      Results were analyzed using a mixed model (SAS 9.4). Breast muscle pH and R-value
      did not differ between genetic lines, and there were no differences in pH and R
      value among clusters within genetic lines. These findings suggest that OF
      responses measured during rearing are not related to PM breast muscle pH and R
      value, which ultimately affect meat quality. Further research is needed to assess
      whether other types of fear responses are associated with meat quality and
      whether differences in R-value between genetic lines are associated with
      differences in other meat quality characteristics.

PMID- 26195808
TI  - Pharmacokinetic and pharmacodynamic properties of gamithromycin in turkey poults
      with respect to Ornithobacterium rhinotracheale.
AB  - The macrolide gamithromycin (GAM) has the ability to accumulate in tissues of the
      respiratory tract. Consequently, GAM might be a suitable antibiotic to treat
      bacterial respiratory infections in poultry, such as Ornithobacterium
      rhinotracheale. As O. rhinotracheale infections are common in turkey flocks, the
      aim of this study was to determine the pharmacokinetic (PK) parameters of GAM in
      plasma, lung tissue, and pulmonary epithelial lining fluid (PELF) of turkeys and
      to correlate them with pharmacodynamic (PD) characteristics (PK/PD). The animal
      experiment was performed with 64 turkeys, which received either a subcutaneous
      (SC, n=32) or an oral (PO, n=32) bolus of 6 mg GAM/kg body weight (BW). GAM
      concentrations in plasma, lung tissue, and PELF were measured at different time
      points post administration (p.a.), and PK characteristics were determined using
      non-compartmental modeling. The maximum plasma concentration after PO
      administration was ten-fold lower than after SC injection (0.087 and 0.89 MUg/mL,
      respectively), whereas there was no difference in lung concentrations between
      both routes of administration. However, lung concentrations at day 1 p.a. were
      significantly higher than plasma levels for both routes of administration (2.22
      and 3.66 MUg/g for PO and SC, respectively). Consequently, lung/plasma ratios
      were high, up to 50 and 80 after PO and SC administration, respectively. GAM
      could not be detected in PELF, although this might be attributed to the
      collection method of PELF in birds. The GAM minimum inhibitory concentration
      (MIC) was determined for 38 O. rhinotracheale strains; MIC50 and MIC90 were 2 and
      >32 MUg/mL, respectively. PK/PD correlation for lung tissue demonstrated that the
      time above the MIC90 of the susceptible population (2 MUg/mL) was 1 day after PO
      bolus and 3.5 days after SC administration. The area under the curve
      (AUClast)/MIC ratios for lung tissue after SC and PO administration were 233 and
      90, respectively. To conclude, GAM is highly distributed to lung tissue in turkey
      poults, suggesting that it has the potential to be used to treat respiratory
      infections such as O. rhinotracheale.

PMID- 26195809
TI  - Enzymatic hydrolysis of ovomucoid and the functional properties of its
      hydrolysates.
AB  - Ovomucoid is well known as a "trypsin inhibitor" and is considered to be the main
      food allergen in egg. However, the negative functions of ovomucoid can be
      eliminated if the protein is cut into small peptides. The objectives of this
      study were to hydrolyze ovomucoid using various enzyme combinations, and compare
      the functional properties of the hydrolysates. Purified ovomucoid was dissolved
      in distilled water (20 mg/mL) and treated with 1% of pepsin, alpha-chymotrypsin,
      papain, and alcalase, singly or in combinations. Sodium sodium dodecyl sulfate
      polyacrylamide (SDS-PAGE) results of the hydrolysates indicated that pepsin
      (OMP), alcalase (OMAl), alcalase+trypsin (OMAlTr), and alcalase+papain (OMAlPa)
      treatments best hydrolyzed the ovomucoid, and the 4 treatments were selected to
      determine their functional characteristics. Among the 4 enzyme treatments,
      hydrolysate from OMAlTr showed the highest iron-chelating and antioxidant
      activities, while OMP showed higher ACE-inhibitory activity, but lower Fe
      chelating activity than the other treatments. However, no difference in the
      copper-chelating activity among the treatments was found. MS/MS analysis
      identified numerous peptides from the hydrolysates of OMAlPa and OMAlTr, and
      majority of the peptides produced were <2 kDa. Pepsin treatment (OMP), however,
      hydrolyzed ovomucoid almost completely and produced only amino acid monomers, di-
      and tri-peptides. The ACE-inhibitory, antioxidant and iron-chelating activities
      of the enzyme hydrolysates were not consistent with the number and size of
      peptides in the hydrolysates, but we do not have information about the quantity
      of each peptide present in the hydrolysates at this point.

PMID- 26195810
TI  - Effects of 5-hydroxytryptophan and m-hydroxybenzylhydrazine associated to
      Lactobacillus spp. on the humoral response of broilers challenged with Salmonella
      Enteritidis.
AB  - This study investigates the effects of different doses of serotonin, its
      precursor 5-hydroxytry-ptophan (5HTP), and m-hydroxybenzylhydrazine inhibitor
      (NSD1015), administered via intraperitoneal for 5 consecutive days, on behavior
      and average body weight of broilers. We also measured the humoral immune response
      and quantification of Salmonella Enteritidis in broilers chickens that received
      the drugs evaluated and a Lactobacillus pool. The study was divided into 3
      experiments: Experiment 1--administration of pharmaceuticals with choice of
      dosage; Experiment 2--administration of pharmaceuticals and a Lactobacillus pool
      in birds that were not challenged with S. Enteritidis, and Experiment 3-
      administration of pharmaceuticals and a Lactobacillus pool in birds challenged
      with S. Enteritidis. The ELISA was used to scan dosages of intestinal IgA and
      serum IgY. We used colony-forming units to quantify S. Enteritidis. The
      concentrations of IgA and IgY did not show significant differences (P>0.05) in
      Experiment 2. In Experiment 3, NSD1015 associated with Lactobacillus determined
      higher IgA concentrations, promoting greater stimulus to the immune system than
      5HTP. Regarding quantification of S. Enteritidis in the cecal content of birds,
      5HTP associated to Lactobacillus determined the smallest number of bacteria,
      showing possible interaction of 5-hydroxytryptophan and Lactobacillus spp. with
      the immune system of broiler chickens.

PMID- 26195811
TI  - STAT5 Orchestrates Local Epigenetic Changes for Chromatin Accessibility and
      Rearrangements by Direct Binding to the TCRgamma Locus.
AB  - The transcription factor STAT5, which is activated by IL-7R, controls chromatin
      accessibility and rearrangements of the TCRgamma locus. Although STAT-binding
      motifs are conserved in Jgamma promoters and Egamma enhancers, little is known
      about their precise roles in rearrangements of the TCRgamma locus in vivo. To
      address this question, we established two lines of Jgamma1 promoter mutant mice:
      one harboring a deletion in the Jgamma1 promoter, including three STAT motifs
      (Jgamma1P(Delta/Delta)), and the other carrying point mutations in the three STAT
      motifs in that promoter (Jgamma1P(mS/mS)). Both Jgamma1P(Delta/Delta) and
      Jgamma1P(mS/mS) mice showed impaired recruitment of STAT5 and chromatin
      remodeling factor BRG1 at the Jgamma1 gene segment. This resulted in severe and
      specific reduction in germline transcription, histone H3 acetylation, and histone
      H4 lysine 4 methylation of the Jgamma1 gene segment in adult thymus.
      Rearrangement and DNA cleavage of the segment were severely diminished, and
      Jgamma1 promoter mutant mice showed profoundly decreased numbers of gammadelta T
      cells of gamma1 cluster origin. Finally, compared with controls, both mutant mice
      showed a severe reduction in rearrangements of the Jgamma1 gene segment,
      perturbed development of gammadelta T cells of gamma1 cluster origin in fetal
      thymus, and fewer Vgamma3(+) dendritic epidermal T cells. Furthermore,
      interaction with the Jgamma1 promoter and Egamma1, a TCRgamma enhancer, was
      dependent on STAT motifs in the Jgamma1 promoter. Overall, this study strongly
      suggests that direct binding of STAT5 to STAT motifs in the Jgamma promoter is
      essential for local chromatin accessibility and Jgamma/Egamma chromatin
      interaction, triggering rearrangements of the TCRgamma locus. 

PMID- 26195812
TI  - Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory
      Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus.
AB  - CD8(+) T cells that recognize virus-derived peptides presented on MHC class I are
      vital antiviral effectors. Such peptides presented by any given virus vary
      greatly in immunogenicity, allowing them to be ranked in an immunodominance
      hierarchy. However, the full range of parameters that determine immunodominance
      and the underlying mechanisms remain unknown. In this study, we show across a
      range of vaccinia virus strains, including the current clonal smallpox vaccine,
      that the ability of a strain to spread systemically correlated with reduced
      immunodominance. Reduction in immunodominance was observed both in the lymphoid
      system and at the primary site of infection. Mechanistically, reduced
      immunodominance was associated with more robust priming and especially priming in
      the spleen. Finally, we show this is not just a property of vaccine and
      laboratory strains of virus, because an association between virulence and
      immunodominance was also observed in isolates from an outbreak of zoonotic
      vaccinia virus that occurred in Brazil.

PMID- 26195813
TI  - Multiple Cathepsins Promote Pro-IL-1beta Synthesis and NLRP3-Mediated IL-1beta
      Activation.
AB  - Sterile particles induce robust inflammatory responses that underlie the
      pathogenesis of diseases like silicosis, gout, and atherosclerosis. A key
      cytokine mediating this response is IL-1beta. The generation of bioactive IL
      1beta by sterile particles is mediated by the NOD-like receptor containing a
      pyrin domain 3 (NLRP3) inflammasome, although exactly how this occurs is
      incompletely resolved. Prior studies have found that the cathepsin B inhibitor,
      Ca074Me, suppresses this response, supporting a model whereby ingested particles
      disrupt lysosomes and release cathepsin B into the cytosol, somehow activating
      NLRP3. However, reports that cathepsin B-deficient macrophages have no defect in
      particle-induced IL-1beta generation have questioned cathepsin B's involvement.
      In this study, we examine the hypothesis that multiple redundant cathepsins (not
      just cathepsin B) mediate this process by evaluating IL-1beta generation in
      murine macrophages, singly or multiply deficient in cathepsins B, L, C, S and X.
      Using an activity-based probe, we measure specific cathepsin activity in living
      cells, documenting compensatory changes in cathepsin-deficient cells, and
      Ca074Me's dose-dependent cathepsin inhibition profile is analyzed in parallel
      with its suppression of particle-induced IL-1beta secretion. Also, we evaluate
      endogenous cathepsin inhibitors cystatins C and B. Surprisingly, we find that
      multiple redundant cathepsins, inhibited by Ca074Me and cystatins, promote pro-IL
      1beta synthesis, and to our knowledge, we provide the first evidence that
      cathepsin X plays a nonredundant role in nonparticulate NLRP3 activation.
      Finally, we find cathepsin inhibitors selectively block particle-induced NLRP3
      activation, independently of suppressing pro-IL-1beta synthesis. Altogether, we
      demonstrate that both small molecule and endogenous cathepsin inhibitors suppress
      particle-induced IL-1beta secretion, implicating roles for multiple cathepsins in
      both pro-IL-1beta synthesis and NLRP3 activation. 

PMID- 26195814
TI  - Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on
      Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype.
AB  - Antiretroviral therapy (ART) induces rapid suppression of viral replication and a
      progressive replenishment of CD4(+) T cells in HIV-infected individuals. However,
      the effect of ART on restoring pre-existing memory CD4(+) T cells specific for
      common copathogens is still unclear. To better understand the dynamics of Ag
      specific CD4(+) T cells during ART, we assessed the frequency, functional
      capacity, and memory profile of CD4(+) T cells specific for Mycobacterium
      tuberculosis and CMV in 15 HIV-infected individuals before and 1 y after ART
      initiation. After ART initiation, the frequency of M. tuberculosis-specific
      CD4(+) T cells showed little change, whereas CMV-specific CD4(+) T cells were
      significantly lower (p = 0.003). There was no difference in the polyfunctional or
      memory profile of Ag-specific CD4(+) T cells before and after ART. The
      replenishment of Ag-specific CD4(+) T cells correlated with the memory
      differentiation profile of these cells prior to ART. Pathogen-specific CD4(+) T
      cells exhibiting a late differentiated profile (CD45RO(+)CD27(-)) had a lower
      capacity to replenish (p = 0.019; r = -0.5) compared with cells with an early
      differentiated profile (CD45RO(+)CD27(+); p = 0.04; r = 0.45). In conclusion,
      restoration of copathogen-specific memory CD4(+) T cells during treated HIV
      infection is related to their memory phenotype, in which early differentiated
      cells (such as most M. tuberculosis-specific cells) have a higher replenishment
      capacity compared with late differentiated cells (such as most CMV-specific
      cells). These data identify an important, hitherto unrecognized, factor that may
      limit restoration of copathogen immunity in HIV-infected individuals on ART.

PMID- 26195815
TI  - The Contained Self-Reactive Peripheral T Cell Repertoire: Size, Diversity, and
      Cellular Composition.
AB  - Individual self-reactive T cells have been discovered in both humans and mice. It
      is difficult to assess the entire contained self-reactive peripheral T cell
      repertoire in healthy individuals because regulatory T cells (Tregs) can render
      these cells anergic and, therefore, functionally indistinguishable. We addressed
      this issue by removing regulatory T cells, thereby allowing us to characterize
      the exposed self-reactive T cells. This resulted in activation of approximately
      4% of both CD4(+) and CD8(+) T cells. Activation and division of these cells was
      not a bystander product of Ag-independent signals but required TCR stimulation.
      Analysis of TCR sequences showed that these responding cells were polyclonal and
      encompassed a broad range of structural TCR diversity. Adoptive transfer of naive
      and effector/memory T cell populations showed that even the naive T cell pool
      contained self-reactive T cell precursors. In addition, transfer of mature
      thymocytes showed that this response was an intrinsic T cell property rather than
      a peripheral adaptation. Finally, we found that the unexpectedly strong
      contribution of the naive CD5(low) T cell pool showed that the overall self
      reactive response has not only a diverse polyclonal TCR repertoire, but also
      comprises a broad range of affinities for self.

PMID- 26195816
TI  - The high-resolution crystal structure of human LCAT.
AB  - LCAT is intimately involved in HDL maturation and is a key component of the
      reverse cholesterol transport (RCT) pathway which removes excess cholesterol
      molecules from the peripheral tissues to the liver for excretion. Patients with
      loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal
      opacity. Here we report the 2.65 A crystal structure of the human LCAT protein.
      Crystallization required enzymatic removal of N-linked glycans and complex
      formation with a Fab fragment from a tool antibody. The crystal structure reveals
      that LCAT has an alpha/beta hydrolase core with two additional subdomains that
      play important roles in LCAT function. Subdomain 1 contains the region of LCAT
      shown to be required for interfacial activation, while subdomain 2 contains the
      lid and amino acids that shape the substrate binding pocket. Mapping the
      naturally occurring mutations onto the structure provides insight into how they
      may affect LCAT enzymatic activity. 

PMID- 26195817
TI  - Angiogenin Mediates Cell-Autonomous Translational Control under Endoplasmic
      Reticulum Stress and Attenuates Kidney Injury.
AB  - Endoplasmic reticulum (ER) stress is involved in the pathophysiology of kidney
      disease and aging, but the molecular bases underlying the biologic outcomes on
      the evolution of renal disease remain mostly unknown. Angiogenin (ANG) is a
      ribonuclease that promotes cellular adaptation under stress but its contribution
      to ER stress signaling remains elusive. In this study, we investigated the ANG
      mediated contribution to the signaling and biologic outcomes of ER stress in
      kidney injury. ANG expression was significantly higher in samples from injured
      human kidneys than in samples from normal human kidneys, and in mouse and rat
      kidneys, ANG expression was specifically induced under ER stress. In human renal
      epithelial cells, ER stress induced ANG expression in a manner dependent on the
      activity of transcription factor XBP1, and ANG promoted cellular adaptation to ER
      stress through induction of stress granules and inhibition of translation.
      Moreover, the severity of renal lesions induced by ER stress was dramatically
      greater in ANG knockout mice (Ang(-/-)) mice than in wild-type mice. These
      results indicate that ANG is a critical mediator of tissue adaptation to kidney
      injury and reveal a physiologically relevant ER stress-mediated adaptive
      translational control mechanism. 

PMID- 26195819
TI  - Selective peripheral denervation for cervical dystonia: a historical procedure in
      the age of deep brain stimulation?

PMID- 26195818
TI  - Quantitative Micro-Computed Tomography Imaging of Vascular Dysfunction in
      Progressive Kidney Diseases.
AB  - Progressive kidney diseases and renal fibrosis are associated with endothelial
      injury and capillary rarefaction. However, our understanding of these processes
      has been hampered by the lack of tools enabling the quantitative and noninvasive
      monitoring of vessel functionality. Here, we used micro-computed tomography (uCT)
      for anatomical and functional imaging of vascular alterations in three murine
      models with distinct mechanisms of progressive kidney injury: ischemia
      reperfusion (I/R, days 1-56), unilateral ureteral obstruction (UUO, days 1-10),
      and Alport mice (6-8 weeks old). Contrast-enhanced in vivo uCT enabled robust,
      noninvasive, and longitudinal monitoring of vessel functionality and revealed a
      progressive decline of the renal relative blood volume in all models. This
      reduction ranged from -20% in early disease stages to -61% in late disease stages
      and preceded fibrosis. Upon Microfil perfusion, high-resolution ex vivo uCT
      allowed quantitative analyses of three-dimensional vascular networks in all three
      models. These analyses revealed significant and previously unrecognized
      alterations of preglomerular arteries: a reduction in vessel diameter, a
      prominent reduction in vessel branching, and increased vessel tortuosity. In
      summary, using uCT methodology, we revealed insights into macro-to-microvascular
      alterations in progressive renal disease and provide a platform that may serve as
      the basis to evaluate vascular therapeutics in renal disease. 

PMID- 26195820
TI  - RIP1 Cleavage in the Kinase Domain Regulates TRAIL-Induced NF-kappaB Activation
      and Lymphoma Survival.
AB  - Although TRAIL is considered a potential anticancer agent, it enhances tumor
      progression by activating NF-kappaB in apoptosis-resistant cells. Cellular FLICE
      like inhibitory protein (cFLIP) overexpression and caspase-8 activation have been
      implicated in TRAIL-induced NF-kappaB activation; however, the underlying
      mechanisms are unknown. Here, we report that caspase-8-dependent cleavage of RIP1
      in the kinase domain (KD) and intermediate domain (ID) determines the activation
      state of the NF-kappaB pathway in response to tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) treatment. In apoptosis-sensitive cells,
      caspase-8 cleaves RIP1 in the KD and ID immediately after the recruitment of RIP1
      to the receptor complex, impairing IkappaB kinase (IKK) recruitment and NF-kappaB
      activation. In apoptosis-resistant cells, cFLIP restricts caspase-8 activity,
      resulting in limited RIP1 cleavage and generation of a KD-cleaved fragment
      capable of activating NF-kappaB but not apoptosis. Notably, depletion of the
      cytoplasmic pool of TRAF2 and cIAP1 in lymphomas by CD40 ligation inhibits basal
      RIP1 ubiquitination but does not prompt cell death, due to CD40L-induced cFLIP
      expression and limited RIP1 cleavage. Inhibition of RIP1 cleavage at the KD
      suppresses NF-kappaB activation and cell survival even in cFLIP-overexpressing
      lymphomas. Importantly, RIP1 is constitutively cleaved in human and mouse
      lymphomas, suggesting that cFLIP-mediated and caspase-8-dependent limited
      cleavage of RIP1 is a new layer of mechanism that promotes NF-kappaB activation
      and lymphoma survival. 

PMID- 26195821
TI  - Orphan Nuclear Receptor Nur77 Inhibits Cardiac Hypertrophic Response to Beta
      Adrenergic Stimulation.
AB  - The orphan nuclear receptor Nur77 plays critical roles in cardiovascular
      diseases, and its expression is markedly induced in the heart after beta
      adrenergic receptor (beta-AR) activation. However, the functional significance of
      Nur77 in beta-AR signaling in the heart remains unclear. By using Northern blot,
      Western blot, and immunofluorescent staining assays, we showed that Nur77
      expression was markedly upregulated in cardiomyocytes in response to multiple
      hypertrophic stimuli, including isoproterenol (ISO), phenylephrine (PE), and
      endothelin-1 (ET-1). In a time- and dose-dependent manner, ISO increases Nur77
      expression in the nuclei of cardiomyocytes. Overexpression of Nur77 markedly
      inhibited ISO-induced cardiac hypertrophy by inducing nuclear translocation of
      Nur77 in cardiomyocytes. Furthermore, cardiac overexpression of Nur77 by
      intramyocardial injection of Ad-Nur77 substantially inhibited cardiac hypertrophy
      and ameliorated cardiac dysfunction after chronic infusion of ISO in mice.
      Mechanistically, we demonstrated that Nur77 functionally interacts with NFATc3
      and GATA4 and inhibits their transcriptional activities, which are critical for
      the development of cardiac hypertrophy. These results demonstrate for the first
      time that Nur77 is a novel negative regulator for the beta-AR-induced cardiac
      hypertrophy through inhibiting the NFATc3 and GATA4 transcriptional pathways.
      Targeting Nur77 may represent a potentially novel therapeutic strategy for
      preventing cardiac hypertrophy and heart failure. 

PMID- 26195822
TI  - Developmental Switch in the Transcriptional Activity of a Long-Range Regulatory
      Element.
AB  - Eukaryotic gene expression is often controlled by distant regulatory elements. In
      developing B lymphocytes, transcription is associated with V(D)J recombination at
      immunoglobulin loci. This process is regulated by remote cis-acting elements. At
      the immunoglobulin heavy chain (IgH) locus, the 3' regulatory region (3'RR)
      promotes transcription in mature B cells. This led to the notion that the 3'RR
      orchestrates the IgH locus activity at late stages of B cell maturation only.
      However, long-range interactions involving the 3'RR were detected in early B
      cells, but the functional consequences of these interactions were unknown. Here
      we show that not only does the 3'RR affect transcription at distant sites within
      the IgH variable region but also it conveys a transcriptional silencing activity
      on both sense and antisense transcription. The 3'RR-mediated silencing activity
      is switched off upon completion of VH-DJH recombination. Our findings reveal a
      developmentally controlled, stage-dependent shift in the transcriptional activity
      of a master regulatory element. 

PMID- 26195825
TI  - ATP stimulates pannexin 1 internalization to endosomal compartments.
AB  - The ubiquitous pannexin 1 (Panx1) ion- and metabolite-permeable channel mediates
      the release of ATP, a potent signalling molecule. In the present study, we
      provide striking evidence that ATP, in turn, stimulates internalization of Panx1
      to intracellular membranes. These findings hold important implications for
      understanding the regulation of Panx1 when extracellular ATP is elevated. In the
      nervous system, this includes phenomena such as synaptic plasticity, pain,
      precursor cell development and stroke; outside of the nervous system, this
      includes things like skeletal and smooth muscle activity and inflammation. Within
      15 min, ATP led to significant Panx1-EGFP internalization. In a series of
      experiments, we determined that hydrolysable ATP is the most potent stimulator of
      Panx1 internalization. We identified two possible mechanisms for Panx1
      internalization, including activation of ionotropic purinergic (P2X) receptors
      and involvement of a putative ATP-sensitive residue in the first extracellular
      loop of Panx1 (Trp(74)). Internalization was cholesterol-dependent, but clathrin,
      caveolin and dynamin independent. Detailed analysis of Panx1 at specific endosome
      sub-compartments confirmed that Panx1 is expressed in endosome membranes of the
      classical degradation pathway under basal conditions and that elevation of ATP
      levels diverts a sub-population to recycling endosomes. This is the first report
      detailing endosome localization of Panx1 under basal conditions and the potential
      for ATP regulation of its surface expression. Given the ubiquitous expression
      profile of Panx1 and the importance of ATP signalling, these findings are of
      critical importance for understanding the role of Panx1 in health and disease.

PMID- 26195824
TI  - DNA cytosine and methylcytosine deamination by APOBEC3B: enhancing methylcytosine
      deamination by engineering APOBEC3B.
AB  - APOBEC (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like) is a
      family of enzymes that deaminates cytosine (C) to uracil (U) on nucleic acid.
      APOBEC3B (A3B) functions in innate immunity against intrinsic and invading
      retroelements and viruses. A3B can also induce genomic DNA mutations to cause
      cancer. A3B contains two cytosine deaminase domains (CD1, CD2), and there are
      conflicting reports about whether both domains are active. Here we demonstrate
      that only CD2 of A3B (A3BCD2) has C deamination activity. We also reveal that
      both A3B and A3BCD2 can deaminate methylcytosine (mC). Guided by structural and
      functional analysis, we successfully engineered A3BCD2 to gain over two orders of
      magnitude higher activity for mC deamination. Important determinants that
      contribute to the activity and selectivity for mC deamination have been
      identified, which reveals that multiple elements, rather than single ones,
      contribute to the mC deamination activity and selectivity in A3BCD2 and possibly
      other APOBECs. 

PMID- 26195826
TI  - Formation of the ether lipids archaetidylglycerol and archaetidylethanolamine in
      Escherichia coli.
AB  - In archaea, the membrane phospholipids consist of isoprenoid hydrocarbon chains
      that are ether-linked to a sn-glycerol1-phosphate backbone. This unique structure
      is believed to be vital for the adaptation of these micro-organisms to extreme
      environments, but it also reflects an evolutionary marker that distinguishes
      archaea from bacteria and eukaryotes. CDP-archaeol is the central precursor for
      polar head group attachment. We examined various bacterial enzymes involved in
      the attachment of L-serine and glycerol as polar head groups for their
      promiscuity in recognizing CDP-archaeol as a substrate. Using a combination of
      mutated bacterial and archaeal enzymes, archaetidylethanolamine (AE) and
      archaetidylglycerol (AG) could be produced in vitro using nine purified enzymes
      while starting from simple building blocks. The ether lipid pathway constituted
      by a set of archaeal and bacterial enzymes was introduced into Escherichia coli,
      which resulted in the biosynthesis of AE and AG. This is a further step in the
      reprogramming of E. coli for ether lipid biosynthesis.

PMID- 26195823
TI  - The mucolipidosis IV Ca2+ channel TRPML1 (MCOLN1) is regulated by the TOR kinase.
AB  - Autophagy is a complex pathway regulated by numerous signalling events that
      recycles macromolecules and may be perturbed in lysosomal storage disorders
      (LSDs). During autophagy, aberrant regulation of the lysosomal Ca(2+) efflux
      channel TRPML1 [transient receptor potential mucolipin 1 (MCOLN1)], also known as
      MCOLN1, is solely responsible for the human LSD mucolipidosis type IV (MLIV);
      however, the exact mechanisms involved in the development of the pathology of
      this LSD are unknown. In the present study, we provide evidence that the target
      of rapamycin (TOR), a nutrient-sensitive protein kinase that negatively regulates
      autophagy, directly targets and inactivates the TRPML1 channel and thereby
      functional autophagy, through phosphorylation. Further, mutating these
      phosphorylation sites to unphosphorylatable residues proved to block TOR
      regulation of the TRPML1 channel. These findings suggest a mechanism for how TOR
      activity may regulate the TRPML1 channel.

PMID- 26195827
TI  - Shoulder arthroscopy and complications: Can we afford to relax?

PMID- 26195828
TI  - Minimally invasive approach to calcified aortic valve replacement: Anaesthetic
      considerations.
AB  - For symptomatic patients with severe calcified aortic valve stenosis, open heart
      surgery for aortic valve replacement remains the gold standard. However, elderly
      patients with an increased risk profile can be treated by using transcatheter
      approaches (transcatheter aortic valve implantation [TAVI]). The major
      considerations related to use of general and local anaesthesia for TAVI are
      discussed in this review. 

PMID- 26195829
TI  - Effect of peri-operative intravenous infusion of lignocaine on haemodynamic
      responses to intubation, extubation and post-operative analgesia.
AB  - BACKGROUND AND AIMS: Lignocaine in intravenous (IV) bolus dose has been used for
      minimising haemodynamic changes associated with intubation and extubation.
      Furthermore, IV infusion has been used for post-operative analgesia. We
      investigated whether IV peri-operative lignocaine (bolus and infusion) would be
      able to produce both the effects simultaneously in elective laparoscopic
      cholecystectomies. METHODS: In this randomised prospective study, 60 patients
      undergoing elective laparoscopic cholecystectomy were randomly divided into two
      groups of 30 each. In Group A, patients received 6 ml normal saline as bolus over
      10 min followed by 6 ml/h infusion whereas in Group B, patients received
      preservative free 2% lignocaine 1.5 mg/kg IV bolus (made to a volume of 6 ml with
      normal saline) administered over a period of 10 min and thereafter an infusion at
      a rate of 1.5 mg/kg/h (pre-diluted in normal saline made to a volume of 6 ml/h. P
      < 0.05 was considered as significant. RESULTS: The rise in pulse rate (PR) and
      mean arterial pressure (MAP) were less in Group B as compared to the Group A (P <
      0.05) during intubation as well as during extubation. Furthermore, the Group B
      had significant longer mean pain-free post-operative period of 51/2 h as compared
      to 54.43 min in the Group A (P < 0.05). CONCLUSION: Administration of lignocaine
      infusion attenuates the rise in PR as well as MAP during the peri-intubation and
      peri-extubation period. Furthermore, infusion of lignocaine significantly
      increases the mean pain-free period post-operatively.

PMID- 26195830
TI  - Comparison of electroencephalogram entropy versus loss of verbal response to
      determine the requirement of propofol for induction of general anaesthesia.
AB  - BACKGROUND AND AIMS: Propofol causes dose-dependent reduction in blood pressure
      (BP). This study was done to evaluate the use of spectral entropy on the dose of
      propofol required and the haemodynamic stability during induction of general
      anaesthesia (GA). METHODS: In this randomised controlled study, 72 American
      Society of Anesthesiologists' physical status I and II patients undergoing
      general and orthopaedic surgeries were divided into Group S (n-36) and Group C (n
      36). Patients in Group C were induced with propofol till loss of response to
      verbal commands and in Group S until the state entropy was <50 and state and
      response entropy difference was <10. The induction dose of propofol, haemodynamic
      parameters and the entropy values were recorded. Numerical data were expressed as
      a mean +/- standard deviation and analysed using unpaired, two-tailed t-test.
      Categorical data were compared using Chi-square test. P < 0.05 value was
      considered significant. RESULTS: The dose of propofol per kg was significantly
      more in the entropy group (1.80 +/- 0.23 mg/kg in the Group C and 1.98 +/- 0.217
      mg/kg in the Group S [P < 0.05]). After induction, at intubation and 1 min after
      intubation, entropy values were lower in Group S than Group C (P < 0.05). The BP
      decreased significantly after induction compared with the baseline (P < 0.05),
      but there was no difference between the groups. CONCLUSION: Propofol required for
      induction of GA when guided by electroencephalogram entropy was significantly
      higher than the induction dose based on loss of verbal response. Both
      conventional induction and induction with entropy as the endpoint resulted in
      similar haemodynamic profile.

PMID- 26195831
TI  - Effect of intravenous ondansetron on reducing the incidence of hypotension and
      bradycardia events during shoulder arthroscopy in sitting position under
      interscalene brachial plexus block: A prospective randomized trial.
AB  - BACKGROUND AND AIMS: Sudden, profound hypotension and bradycardia events (HBEs)
      have been reported in more than 20% of patients undergoing shoulder arthroscopy
      in the sitting position. The present study was designed to know whether
      intravenous (IV) ondansetron (selective 5-hydroxy tryptamine 3-antagonist) can
      help in reducing the HBEs associated with shoulder arthroscopy performed in
      sitting position under interscalene brachial plexus block (ISBPB). METHODS: A
      total of 100 patients (age 20-50 years) undergoing shoulder arthroscopy performed
      in the sitting position under ISBPB were assigned randomly to one of the two
      groups: Group C received 10 ml of normal saline and Group T received 4 mg of
      ondansetron diluted in 10 ml of normal saline' IV. All patients received ISBPB
      using levobupivacaine 0.5%. Assessment of motor and sensory blockade, pulse rate,
      systolic blood pressure, respiration, and side effects were noted every 5 min for
      first 30 min and every 10 min till the end of surgery. HBEs were recorded in both
      groups. RESULTS: IV injection of ondansetron significantly reduces the incidence
      of HBEs from 11 (22.44% in Group C) to 3 (6.1% in Group T). The duration of
      analgesia was significantly longer in Group C (8.1 +/- 3.3) in comparison with
      Group T (6.3 +/- 4.2 h). CONCLUSION: We conclude that 4 ml of IV ondansetron can
      significantly reduce the HBEs during shoulder arthroscopy done in the sitting
      position under ISBPB.

PMID- 26195832
TI  - Is dexmedetomidine better than propofol and fentanyl combination in minor day
      care procedures? A prospective randomised double-blind study.
AB  - BACKGROUND AND AIMS: The growing popularity and trend of day care (ambulatory)
      anaesthesia has led to the development of newer and efficient drug regimen. We
      decided to evaluate the efficacy of two drug regimens namely dexmedetomidine and
      propofol with midazolam and fentanyl for moderate sedation characteristics in
      minor surgical procedures in terms of analgesia, intra-operative sedation,
      haemodynamic stability and side effects related. METHODS: Totally, 60 adult
      American Society of Anaesthesiologists class I-II patients posted for day care
      surgeries of duration <45 min divided into two groups; Group D, where
      dexmedetomidine loading dose at 1 MUg/kg was administered over 10 min followed by
      maintenance infusion initiated at 0.6 MUg/kg/h and titrated to achieve desired
      clinical effect with dose ranging from 0.2 to 0.7 MUg/kg, Group P, where
      midazolam at 0.02 mg/kg and fentanyl at 2 MUg/kg IV boluses were given followed
      by propofol infusion. Statistical analysis was done using student t-test,
      analysis of variance and Chi-square analysis. P < 0.05 was considered to be
      significant. RESULTS: Degree of sedation (Observer's Assessment of Activity and
      Sedation Scale <=3) was comparable in both groups (P > 0.05). Rescue analgesia
      with fentanyl was needed in 30% patients of Group D compared to 17.63% patients
      of Group P (P < 0.05). The level of arousal was faster and better in Group D at 5
      min after the procedure (P < 0.05). Haemodynamics were stable in Group D as with
      Group P patients (P < 0.005). Dry mouth reported by 16.67% patients. CONCLUSION:
      Dexmedetomidine can be a useful adjuvant rather than the sole sedative-analgesic
      agent during minor surgeries and be a valuable alternative to propofol in terms
      of moderate sedation, haemodynamic stability with minimal transient side effects.

PMID- 26195833
TI  - Change in neck circumference after shoulder arthroscopy: An observational study.
AB  - BACKGROUND AND AIMS: Shoulder arthroscopy requires fluid irrigation, which causes
      soft-tissue oedema around chest, neck, and arm intraoperatively, leading to
      postoperative airway complications. We decided to study the incidence of increase
      in the neck circumference in shoulder arthroscopy and its effects on the airway.
      METHODS: We studied 32 cases of shoulder arthroscopies over a period of 1-year,
      performed under general anaesthesia with interscalene block. The neck
      circumference of patients before and after the procedure was measured along with
      other parameters. The endotracheal tube cuff was deflated at the end of surgery
      to determine air leak around the tube. The negative leak test suggested airway
      oedema. RESULTS: Thirty out of 32 patients showed positive air leak test. The
      average change in neck circumference was 1.17 +/- 1.16 cm and all could be
      extubated uneventfully. Two showed negative leak test with an increase in neck
      circumference by 4.5 and 6.4 cm and were not extubated. Multiple regression
      analysis for risk factors showed intraoperative hypertension as a single
      predictor for an increase in neck circumference. CONCLUSION: Change in the neck
      circumference beyond 4 cm may suggest airway compromise and below 4 cm, airway
      compromise is unlikely even in the presence of extensive soft-tissue oedema
      around the shoulder, upper arm and chest.

PMID- 26195834
TI  - Introducing a teaching module to impart communication skills in the learning
      anaesthesiologists.
AB  - BACKGROUND AND AIMS: Pre-operative negative valence communications adversely
      affect intra and post-operative pain experience. This study was conducted to
      evaluate the teaching of communication skills by teachers in anaesthesia
      department and whether the post-operative pain is effectively modified due to the
      skill of communication acquired by students. METHODS: All students and teachers
      in the department participated in the study. Patients with uncomplicated
      pregnancy posted for elective lower segment caesarean section were involved.
      Students were taught to explain the anaesthesia plan pre-operatively to the
      patients in a positive manner. They were taught the practice of giving positive
      suggestions before any potentially painful stimulus. Pre-operatively all students
      informed the patients about the conduct of spinal anaesthesia. The teachers
      evaluated the students performing spinal block. The performance was rated for
      procedural and interpersonal skills (direct observation of procedural skills
      [DOPS] and Smith and Kendall Behavioural scale [SKBS] respectively). The extent
      of cooperation and the ease with which spinal block could be administered
      correctly by the student was judged by the teacher. Post-operatively students
      were randomly provided questionnaires to elicit answers from patients. RESULTS: P
      value DOPS and SKBS (0.567, 0.867) show no significant statistical variation. P >
      0.05 = not significant, indicates no significant variation in procedural and
      behavioural skills of students in two groups. CONCLUSION: Teaching of
      communication skills to students showed a demonstrable effect on their pre
      operative dialogue with patients. Pain mechanism was effectively modulated by
      improving patients' psychology to undergo anaesthesia.

PMID- 26195835
TI  - Prolonged post spinal anaesthesia paralysis.

PMID- 26195836
TI  - Perioperative management of combined surgery for phaeochromocytoma and double
      outlet right ventricle: A rare combination.

PMID- 26195838
TI  - Reversible cause of intra operative hypoxia in an aspirated patient.

PMID- 26195837
TI  - Cerebral vasospasm after selective amygdalohippocampectomy.

PMID- 26195839
TI  - Inside preview of procuring narcotic license.

PMID- 26195840
TI  - Laparoscopic adrenalectomy in a post-pneumonectomy state.

PMID- 26195841
TI  - Acute Compartment Syndrome of the forearm in a patient undergoing coronary artery
      bypass surgery.

PMID- 26195842
TI  - Massive subcutaneous emphysema following laparoscopic nephroureterectomy: An
      unusual presentation.

PMID- 26195843
TI  - Marble bone disease and the Anaesthesiologist.

PMID- 26195844
TI  - Hyperacute onset of Guillain Barre Syndrome in the immediate postpartum period
      following Caesarean section under spinal anaesthesia.

PMID- 26195845
TI  - Unexpected intra-operative bleeding due to Hermansky-Pudlak Syndrome.

PMID- 26195846
TI  - Ultrasound guided Transversus Abdominis Plane block through surgical wound.

PMID- 26195847
TI  - A home brewed low cost cuff inflator and pressure monitor.

PMID- 26195848
TI  - MALDI-TOF/TOF CID Study of Poly(1,4-dihydroxybenzene terephthalate) Fragmentation
      Reactions.
AB  - MALDI-TOF/TOF collision-induced dissociation (CID) experiments were conducted on
      model aromatic polyester oligomers. CID fragmentation studies identified initial
      fracture of the ester bond and subsequent CO loss as a major pathway, consistent
      with the general fragmentation mechanism used to explain the origin of poly(p
      phenylenediamine terephthalamide) (PPD-T) fragment ions. Specifically, both
      charge-remote and charge-site fragmentation were observed. Different parent-ion
      species were observed, the major ones being carboxyl-hydroxyl, di-carboxyl, di
      hydroxyl, and phenyl-carboxyl terminated. One species observed was hydroxyl
      diethylamine terminated caused by reaction of carboxyl groups with triethylamine
      added to the synthesis reaction mixture. Fragment ions reflected the end groups
      of the parent oligomers. Some MALDI fragment-ion spectra were obtained for
      species showing exchange between Li and H at the carboxyl end group. Bond energy
      calculations provide further insight into suggested fragmentation mechanisms.

PMID- 26195849
TI  - Analysis of longitudinal multivariate outcome data from couples cohort studies:
      application to HPV transmission dynamics.
AB  - We consider a specific situation of correlated data where multiple outcomes are
      repeatedly measured on each member of a couple. Such multivariate longitudinal
      data from couples may exhibit multi-faceted correlations which can be further
      complicated if there are polygamous partnerships. An example is data from cohort
      studies on human papillomavirus (HPV) transmission dynamics in heterosexual
      couples. HPV is a common sexually transmitted disease with 14 known oncogenic
      types causing anogenital cancers. The binary outcomes on the multiple types
      measured in couples over time may introduce inter-type, intra-couple, and
      temporal correlations. Simple analysis using generalized estimating equations or
      random effects models lacks interpretability and cannot fully utilize the
      available information. We developed a hybrid modeling strategy using Markov
      transition models together with pairwise composite likelihood for analyzing such
      data. The method can be used to identify risk factors associated with HPV
      transmission and persistence, estimate difference in risks between male-to-female
      and female-to-male HPV transmission, compare type-specific transmission risks
      within couples, and characterize the inter-type and intra-couple associations.
      Applying the method to HPV couple data collected in a Ugandan male circumcision
      (MC) trial, we assessed the effect of MC and the role of gender on risks of HPV
      transmission and persistence.

PMID- 26195850
TI  - Development of Body Part Vocabulary in Toddlers in Relation to Self
      Understanding.
AB  - To better understand young children's ability to communicate about their bodies,
      toddlers' comprehension and production of 27 common body part words was assessed
      using parental report at 20 and 30 months (n = 64), and self-awareness was
      assessed using mirror self-recognition. Children at both ages comprehended more
      body part words that referred to themselves than to others' bodies, and more
      words referring to locations that they could see on themselves than to those they
      could not see. Children with more advanced mirror self-recognition comprehended
      and produced more body part words. These findings suggest that with age and
      better understanding of the self, children also possess a better understanding of
      the body, and they provide new information about factors that affect how young
      children begin to talk about their own and others' bodies. They should be useful
      for practitioners who need to ask children about their bodies and body parts.

PMID- 26195851
TI  - Risks of Large Portfolios.
AB  - The risk of a large portfolio is often estimated by substituting a good estimator
      of the volatility matrix. However, the accuracy of such a risk estimator is
      largely unknown. We study factor-based risk estimators under a large amount of
      assets, and introduce a high-confidence level upper bound (H-CLUB) to assess the
      estimation. The H-CLUB is constructed using the confidence interval of risk
      estimators with either known or unknown factors. We derive the limiting
      distribution of the estimated risks in high dimensionality. We find that when the
      dimension is large, the factor-based risk estimators have the same asymptotic
      variance no matter whether the factors are known or not, which is slightly
      smaller than that of the sample covariance-based estimator. Numerically, H-CLUB
      outperforms the traditional crude bounds, and provides an insightful risk
      assessment. In addition, our simulated results quantify the relative error in the
      risk estimation, which is usually negligible using 3-month daily data.

PMID- 26195852
TI  - Artificial faces are harder to remember.
AB  - Observers interact with artificial faces in a range of different settings and in
      many cases must remember and identify computer-generated faces. In general,
      however, most adults have heavily biased experience favoring real faces over
      synthetic faces. It is well known that face recognition abilities are affected by
      experience such that faces belonging to "out-groups" defined by race or age are
      more poorly remembered and harder to discriminate from one another than faces
      belonging to the "in-group." Here, we examine the extent to which artificial
      faces form an "out-group" in this sense when other perceptual categories are
      matched. We rendered synthetic faces using photographs of real human faces and
      compared performance in a memory task and a discrimination task across real and
      artificial versions of the same faces. We found that real faces were easier to
      remember, but only slightly more discriminable than artificial faces. Artificial
      faces were also equally susceptible to the well-known face inversion effect,
      suggesting that while these patterns are still processed by the human visual
      system in a face-like manner, artificial appearance does compromise the
      efficiency of face processing.

PMID- 26195853
TI  - Dimensions of Parenting Associated with Child Prekindergarten Emotion Regulation
      and Attention Control in Low-income Families.
AB  - Delays in emotion regulation and attention control are common among children
      growing up in poverty, and they contribute to significant socio-economic gaps in
      school readiness and later school attainment. In this study, the emotion
      regulation and attention control skills of 210 prekindergarten Head Start
      participants were assessed (M age = 4.80 years old). Home interviews and
      videotaped parent-child interactions were used to evaluate three aspects of
      parenting (e.g., warm-sensitive, directive-critical, and parenting stress).
      Structural equation models documented significant, unique associations linking
      directive-critical parenting and parenting stress with poor child emotion
      regulation skills. Directive-critical parenting was also uniquely associated with
      low levels of child attention control. Warm-sensitive parenting was not uniquely
      related to either emotion regulation or attention control at this age. The
      findings suggest that, by prekindergarten, parent stress management and reduced
      directiveness emerge as the primary correlates of child emotion regulation and
      attention control, whereas warm-sensitive parenting plays a diminished role.

PMID- 26195854
TI  - Can we predict neurological outcome following out-of-hospital cardiac arrest
      (OHCA) and therapeutic hypothermia?

PMID- 26195855
TI  - Early clinical prediction of neurological outcome following out of hospital
      cardiac arrest managed with therapeutic hypothermia.
AB  - BACKGROUND: Therapeutic hypothermia (TH) may improve neurological outcome in
      comatose patients following out of hospital cardiac arrest (OHCA). The
      reliability of clinical prediction of neurological outcome following TH remains
      unclear. In particular, there is very limited data on survival and predictors of
      neurological outcome following TH for OHCA from resource-constrained settings in
      general and South Asia in specific. OBJECTIVE: The objective was to identify
      factors predicting unfavorable neurological outcome at hospital discharge in
      comatose survivors of OHCA treated with hypothermia. DESIGN: Retrospective chart
      review. SETTING: Urban 200-bed hospital in Chennai, India. METHODS: Predictors of
      unfavorable neurological outcome (cerebral performance category score [3-5]) at
      hospital discharge were evaluated among patients admitted between January 2006
      and December 2012 following OHCA treated with TH. Hypothermia was induced with
      cold intravenous saline bolus, ice packs and cold-water spray with bedside fan.
      Predictors of unfavorable neurological outcome were examined through multivariate
      exact logistic regression analysis. RESULTS: A total of 121 patients were
      included with 106/121 (87%) experiencing the unfavorable neurological outcome.
      Independent predictors of unfavorable neurological outcome included: Status
      myoclonus <24 h (odds ratio [OR] 21.79, 95% confidence interval [CI] 2.89
      Infinite), absent brainstem reflexes (OR 50.09, 6.55-Infinite), and motor
      response worse than flexion on day 3 (OR 99.41, 12.21-Infinite). All 3 variables
      had 100% specificity and positive predictive value. CONCLUSION: Status myoclonus
      within 24 h, absence of brainstem reflexes and motor response worse than flexion
      on day 3 reliably predict unfavorable neurological outcome in comatose patients
      with OHCA treated with TH.

PMID- 26195856
TI  - Pattern of in-hospital pediatric mortality over a 3-year period at University
      teaching hospitals in Iran.
AB  - INTRODUCTION: Causes of death are different and very important for policy makers
      in different regions. This study was designed to analyze the data for our in
      patient children mortality. MATERIALS AND METHODS: In this cross-sectional study
      from March 2011 to March 2013, all patients from 2 months to 18 years who died in
      pediatric intensive care unit, emergency room or medical pediatric wards in the
      teaching hospitals were studied. RESULTS: From a total of 18,915 admissions
      during a 2-year-period, 256 deaths occurred with a mean age of 4.3 +/- 5 years
      and mortality 1.35%. An underlying disease was present in 70.7% of the patients
      and in 88.5% of them the leading causes of death were related to the underlying
      diseases. The most common underlying diseases were congenital heart disease and
      cardiomyopathy in 50 (27.6%). The four main causes of deaths were sepsis (14.8%),
      pneumonia (14.5%), congestive heart failure (9.8%), and hepatic encephalopathy
      (9.8%). CONCLUSION: We may conclude that after sepsis and pneumonia, congestive
      heart failure, and hepatic encephalopathy are the leading causes of death. Most
      patients who died had underlying diseases including malignancies, heart and liver
      diseases as the most common causes.

PMID- 26195857
TI  - Pulmonary-renal syndromes: Experience from an Indian Intensive Care Unit.
AB  - BACKGROUND: The etiology of patients presenting with pulmonary-renal syndrome
      (PRS) to Intensive Care Units (ICUs) in India is not previously reported. AIMS:
      The aim was to describe the prevalence, etiology, clinical manifestations, and
      outcomes of PRS in an Indian ICU and identify variables that differentiate
      immunologic causes of PRS from tropical syndromes presenting with PRS. MATERIALS
      AND METHODS: We conducted a prospective observational study of all patients
      presenting with PRS over 1-year. Clinical characteristics of patients with
      "definite PRS" were compared with those with "PRS mimics". RESULTS: We saw 27
      patients with "provisional PRS" over the said duration; this included 13 patients
      with "definite PRS" and 14 with "PRS mimics". The clinical symptoms were similar,
      but patients with PRS were younger and presented with longer symptom duration.
      Ninety-two percent of the PRS cohort required mechanical ventilation, 77%
      required vasopressors and 61.5% required dialysis within 48 h of ICU admission.
      The etiologic diagnosis of PRS was made after ICU admission in 61.5%. Systemic
      lupus erythrematosus (54%) was the most common diagnosis. A combination of biopsy
      and serology was needed in the majority (69%, 9/13). Pulse methylprednisolone
      (92%) and cyclophosphamide (61.5%) was the most common protocol employed.
      Patients with PRS had more alveolar hemorrhage, hypoxemia and higher mortality
      (69%) when compared to "PRS mimics". CONCLUSION: The spectrum of PRS is different
      in the tropics and tropical syndromes presenting with PRS are not uncommon.
      Multicentric studies are needed to further characterize the burden, etiology,
      treatment protocols, and outcomes of PRS in India.

PMID- 26195858
TI  - Association between a prolonged corrected QT interval and outcomes in patients in
      a medical Intensive Care Unit.
AB  - INTRODUCTION: Patients admitted into a medical Intensive Care Unit (ICU) have
      varying illnesses and risk factors. An electrocardiogram (ECG) is a useful tool
      to assess the cardiac status. The aim of the study was to determine the
      prevalence of QT prolongation of the ECG in patients admitted to a medical ICU in
      a tertiary hospital, to assess outcomes in terms of mortality, cardiovascular
      events, and duration of ICU stay. MATERIALS AND METHODS: Prospective
      observational study, 6 months duration, assessing the prevalence of prolonged
      corrected QT interval (QTc) at admission into a medical ICU. A QTc calculated by
      Bazett's formula, of >440 ms for males and >460 ms for females was considered
      prolonged. Details of illness, clinical and lab parameters were monitored.
      RESULTS: The total number of patients screened was 182. There was a high
      prevalence of prolonged QTc (30%) on admission to the ICU. This reduced to 19% on
      day 3 (P = 0.011). In patients with a prolonged QTc the odds ratio of adverse
      outcome from ICU was 3.17 (confidence interval [CI]: 1.52-6.63) (P = 0.001) and
      of adverse outcome for hospital stay was 2.27 (CI: 1.11-4.66) (P = 0.014). In the
      study, 35% of all patients received drugs with QT prolonging action. Of patients
      with a prolonged QTc at admission 18 (35%) received a QT prolonging drug.
      CONCLUSIONS: We found that prolonged QTc is common (30%) in our medical ICU at
      admission and a large proportion (35%) received drugs capable of prolonging QT
      interval. These patients with QTc prolongation have a higher odds ratio for
      adverse outcomes.

PMID- 26195859
TI  - Invasive candidiasis in non neutropenic critically ill - need for region-specific
      management guidelines.
AB  - Use of antifungal agents has increased over past few decades. A number of risk
      factors such as immunosuppression, broad spectrum antibiotics, dialysis,
      pancreatitis, surgery, etc., have been linked with the increased risk of invasive
      candidiasis. Though there are various guidelines available for the use of
      antifungal therapy, local/regional epidemiology plays an important role in
      determining the appropriate choice of agent in situations where the offending
      organism is not known (i.e. empirical, prophylactic or preemptive therapy).
      Developing countries like India need to generate their own epidemiological data
      to facilitate appropriate use of antifungal therapy. In this article, the authors
      have highlighted the need for region-specific policies/guidelines for treatment
      of invasive candidiasis. Currently available Indian literature on candidemia
      epidemiology has also been summarized here. 

PMID- 26195860
TI  - High-dose versus low-dose antivenom in the treatment of poisonous snake bites: A
      systematic review.
AB  - Though snake antivenom (SAV) is the mainstay of therapy for poisonous snake
      bites, there is no universally accepted standard regimen regarding the optimum
      dose (low vs. high). We therefore, undertook this systematic review to address
      this important research question. We searched all the published literature
      through the major electronic databases till August 2014. Randomized clinical
      trials (RCTs) were included. Eligible trials compared low versus high dose SAV in
      poisonous snake bite. The review has been registered at PROSPERO (Registration
      number: CRD42014009700). Of 36 citations retrieved, a total of 5 RCTs (n = 473)
      were included in the final analyses. Three trials were open-label, 4 conducted in
      Indian sub-continent and 1 in Brazil. The doses of SAV varied in the high dose
      group from 40 ml to 550 ml, and in the low dose group from 20 ml to 220 ml. There
      was no significant difference between the two groups for any of the outcomes
      except duration of hospital stay, which was lower in the low dose group. The
      GRADE evidence generated was of "very low quality." Low-dose SAV is equivalent or
      may be superior to high-dose SAV in management of poisonous snake bite. Low dose
      is also highly cost-effective as compared to the high dose. But the GRADE
      evidence generated was of "very low quality" as most were open label trials.
      Further trials are needed to make definitive recommendations regarding the dose
      and these should also include children <9 years of age. 

PMID- 26195861
TI  - Catheter associated mycobacteremia: Opening new fronts in infection control.
AB  - Mycobacterium fortuitum is a rapidly growing Mycobacterium ubiquitous in nature,
      known to form biofilms. This property increases its propensity to colonize the in
      situ central line and makes it a prospective threat for nosocomial infection. We
      report a case of 48-year-old female with carcinoma cecum who reported to us with
      clinical illness and neutropenia while on chemotherapy via totally implanted
      central venous device, postlaparoscopic-assisted right hemicolectomy. 

PMID- 26195862
TI  - Induced hypothermia for trauma-related ARDS.
AB  - We report a case of 27-year-old male with lung contusions related acute
      respiratory distress syndrome (ARDS) managed by ARDSNet guidelines and additional
      hypothermia. On 4(th) day, post trauma partial pressure of oxygen dropped to 38
      mm of mercury (Hg), not improving even on high positive end-expiratory pressure
      of 18 cm water (H2O), inverse ratio ventilation and fraction of inspired oxygen
      of 1. Extracorporeal membrane oxygenation was ruled out due to the risk of
      hemorrhage from trauma sites. Thereafter, hypothermia along with muscle paralysis
      was considered to reduce total body oxygen consumption. Patient's condition
      improved under hypothermia, and he was extubated and taken up for fracture
      fixation surgeries and discharged later in stable condition. 

PMID- 26195863
TI  - Intranasal midazolam for rapid sedation of an agitated patient.
AB  - Rapidly, establishing a difficult intravenous access in a dangerously agitated
      patient is a real challenge. Intranasal midazolam has been shown to be effective
      and safe for rapidly sedating patients before anesthesia, for procedural sedation
      and for control of seizure. Here, we report a patient in intensive care unit who
      was on mechanical ventilation and on inotropic support for management of septic
      shock and who turned out extremely agitated after accidental catheter removal.
      Intravenous access was successfully established following sedation with
      intranasal midazolam, using ultrasound guidance. 

PMID- 26195864
TI  - Post-operative quadriplegia as the initial manifestation of tumefactive multiple
      sclerosis.
AB  - Post-operative quadriplegia is a rarely encountered complication and not
      previously reported as the initial presentation of tumefactive multiple
      sclerosis. We present an unusual case of a patient with such manifestation and
      atypical lesions on brain magnetic resonance imaging. The patient was treated
      with methyl prednisolone pulse therapy and showed a dramatic response. Uncommon
      neurologic diseases can have very unusual presentations, which should be taken
      into consideration when encountered with such patients. Considering this fact
      will help physicians in better decision-making and proper treatment planning. 

PMID- 26195865
TI  - A response to "stuck suction catheter in endotracheal tube".

PMID- 26195866
TI  - Endotracheal tube cuff leak: Minor product defect or lack of cuff pressure
      monitoring?

PMID- 26195867
TI  - WhatsApp: What an App!

PMID- 26195868
TI  - Accidental placement of central venous catheter tip into internal mammary vein.

PMID- 26195869
TI  - Scrub typhus: Clinical spectrum and outcome.

PMID- 26195870
TI  - Intensive Care Unit mishap during nebulization.

PMID- 26195871
TI  - Scorpion bite, a sting to the heart and to coronaries resulting in Kounis
      syndrome.

PMID- 26195872
TI  - Catheter-based therapy for acute pulmonary embolism: Lifesaving in a clinical
      dilemma!

PMID- 26195873
TI  - Laparoscopic central pancreatectomy: Our technique and long-term results in 14
      patients.
AB  - INTRODUCTION: Conventional pancreatic resections may be unnecessary for benign
      tumours or for tumours of low malignant potential located in the neck and body of
      pancreas. Such extensive resections can place the patient at increased risk of
      developing postoperative exocrine and endocrine insufficiency. Central
      pancreatectomy is a plausible surgical option for the management of tumours
      located in these locations. Laparoscopic approach seems appropriate for such
      small tumours situated deep in the retroperitoneum. AIMS: To assess the technical
      feasibility, safety and long-term results of laparoscopic central pancreatectomy
      in patients with benign and low malignant potential tumours involving the neck
      and body of pancreas. SETTINGS AND DESIGN: This study was an observational study
      which reports a single-centre experience with laparoscopic central pancreatectomy
      over a 9-year period. MATERIALS AND METHODS: 14 patients underwent laparoscopic
      central pancreatectomy from October 2004 to September 2013. These included
      patients with tumours located in the neck and body of pancreas that were
      radiologically benign-looking tumours of less than 3 cm in size. STATISTICAL
      ANALYSIS USED: The statistical analysis was done using GraphPad Prism software.
      RESULTS: The mean age of patients was 48.93 years. The mean operative time was
      239.7 min. Mean blood loss was 153.2 ml. Mean postoperative ICU stay was 1.2 days
      and overall mean hospital stay was 8.07 days. There were no mortalities and no
      major postoperative complications. Margins were negative in all cases and with a
      median follow-up of 44 months, there was no recurrence. CONCLUSIONS: Laparoscopic
      central pancreatectomy is a feasible procedure with acceptable morbidity. In the
      long term, there were no recurrences and pancreatic function was well preserved.

PMID- 26195874
TI  - Comparison of single port and three port laparoscopic splenectomy in patients
      with immune thrombocytopenic purpura: Clinical comparative study.
AB  - AIM: Single-port laparoscopic surgery (SILS) has become increasingly popular
      during the last decades. This prospective study was undertaken to evaluate the
      feasibility of single-port laparoscopic splenectomy compared with conventional
      multiport laparoscopic splenectomy. MATERIALS AND METHODS: Between February 2,
      2009 and August 29, 2011, a total of 40 patients with the diagnosis of immune
      thrombocytopenic purpura were included to study. Patients were alienated into two
      groups according to the procedure type including SILS and conventional multiport
      splenectomy. RESULTS: There were 19 patients in group 1, and 21 in group 2.
      Operative time was significantly shorter in group 1 versus group 2 (112.4 +/-
      13.56 vs 71.2 +/-18.1 minutes, respectively, P < 0.05). One patient in group 1
      had converted to laparatomy due to preoperative bleeding. Postoperative pain
      analyses (VAS Score) revealed superiority of SILS in the early post-operative
      days (P < 0.05). CONCLUSIONS: SILS splenectomy is a safe and effective
      alternative to standard laparoscopic splenectomy.

PMID- 26195875
TI  - Laparoscopic total proctocolectomy with ileal pouch-anal anastomosis for
      ulcerative colitis.
AB  - AIM: The aim was to study the feasibility of the laparoscopic approach in the
      management of ulcerative colitis, to assess the functional results at 1-year and
      to review of literature on the topic. MATERIALS AND METHODS: All patients
      presenting for surgical management of histopathologically proven ulcerative
      colitis during the study period were included in the study. All patients
      presenting in a non-emergency setting were offered a two-stage procedure (Group
      A). The first-stage consisted of laparoscopic total proctocolectomy (TPC) with
      ileal pouch-anal anastomosis (IPAA) with a diverting split end ileostomy.
      Ileostomy was closed in the second stage. For patients presenting in acute
      setting (Group B), the first-stage consisted of laparoscopic TPC with end
      ileostomy followed by IPAA with diverting split end ileostomy in the second-stage
      and finally ileostomy closure in the third-stage. The technique is described.
      RESULTS: A total of 31 cases underwent laparoscopic TPC-IPAA, of which 28
      belonged to Group A and 3 were included in Group B. All surgeries were
      successfully completed laparoscopically without need for conversion. The average
      operating time was 375 min in Group A (range: 270-500 min) and 390 min in Group B
      (range: 250-480 min). Oral diet was resumed at a mean of 3.4 days (range: 1.5-6
      days) and the mean hospital stay was 8.2 days (range: 4-26 days). Overall
      morbidity rate was 16.2%; re-operation rate was 9.7% while mortality was nil.
      CONCLUSIONS: Laparoscopic TPC-IPAA is feasible in acute as well as non-acute
      setting in patients needing surgical management of ulcerative colitis.

PMID- 26195876
TI  - Safety and feasibility of laparoscopic adrenalectomy: What is the role of tumour
      size? A single institution experience.
AB  - BACKGROUND: Although, there are studies in the literature having shown the
      feasibility and safety of laparoscopic adrenalectomy, there are still debates for
      tumour size and the requirement of the minimal invasive approach. Our hypothesis
      was that the use of laparoscopy facilitates minimally invasive resection of large
      adrenal tumours regardless of tumour size. MATERIALS AND METHODS: Within 7 years,
      149 patients underwent laparoscopic adrenalectomy at one institution. The
      patients were divided into two study groups according to tumour size. Group 1
      included patients with adrenal tumours smaller than 5 cm and group 2 included
      larger than 5 cm. Patient demographics and clinical parameters, operative time,
      complications, hospital stay and final pathology were analysed. Statistical
      analyses of clinical and perioperative parameters were performed using Student's
      t-test and Chi-square tests. RESULTS: There were 88 patients in group 1 and 70 in
      group 2. There were no significant differences between study groups regarding
      patient demographics, operative time, hospital stay, and complications. Estimated
      blood loss was significantly higher in group 2 (P = 0.002). The conversion to
      open rate was similar between study groups with 5.6% versus 4.2%, respectively.
      Pathology was similar between groups. CONCLUSION: Our study shows that the use
      laparoscopy for adrenal tumours larger than 5 cm is a safe and feasible
      technique. Laparoscopic adrenalectomy is our preferred minimally invasive
      surgical approach for removing large adrenal tumours.

PMID- 26195877
TI  - Laparoscopic nephrectomy for autosomal dominant polycystic kidneys in patients
      with end-stage renal disease on maintenance hemodialysis: 10-year single surgeon
      experience from an Indian center.
AB  - CONTEXT: Pure laparoscopic nephrectomy in patients with ADPKD (autosomal dominant
      polycystic kidney disease) and ESRD (end-stage renal disease) on MHD (maintenance
      hemodialysis) is challenging with high incidence of complications. Limited
      experiences from India has been reported in these scenarios. AIMS: To present a
      10-year single surgeon experience from India in laparoscopic nephrectomy in
      autosomal dominant polycystic kidneys (ADPKD) and end-stage renal disease (ESRD)
      on maintenance hemodialysis (MHD). SETTINGS AND DESIGN: Retrospective. MATERIALS
      AND METHODS: Retrospective analysis of records of similar subset of patients who
      were offered laparoscopic nephrectomy between 2003 and 2012. Preoperative,
      operative and postoperative parameters were recorded. Few technical modifications
      were adopted over the years. Patients were sub-classified into two groups (Group
      I: 2003-2006, Group II: 2007-2012) based on surgical technique. STATISTICAL
      ANALYSIS USED: SAS software 9.1 version. RESULTS: 75 patients (84 renal units,
      Group I: 31, Group II: 53) were included in this analysis. Unilateral procedure
      was performed in 66 and bilateral staged or simultaneous procedure in 9. Despite
      larger kidneys in Group II (mean longitudinal renal length 25.7 +/- 3.4 vs 17.5
      +/- 2.7 centimeters, P <0.001), improved operative and postoperative profile were
      noted in Group II in several parameters-mean total operative time (205 +/- 11.5
      vs 310 +/- 15.3 min, P = 0.00), time for specimen retrieval (30.5 +/- 3.5 vs 45
      +/- 4.1 min, P = 0.02), postprocedure drop in hemoglobin (1.1 +/- 0.1 vs 2.27 +/-
      0.03 grams/deciliter, P = 0.00). Conversion rates, intraoperative and
      postoperative events were also considerably less in Group II. CONCLUSIONS:
      Despite existence of comorbidities and technical difficulties, laparoscopic
      nephrectomy in patients with ADPKD with ESRD and on MHD is a feasible option.
      Technical modifications with increasing surgeon's experience allows successful
      conductance of this approach in more complex cases with better outcome.

PMID- 26195878
TI  - Comparison of palanosetron with ondansetron for postoperative nausea and vomiting
      in patients undergoing laparoscopic cholecystectomy under general anesthesia.
AB  - BACKGROUND: Post-operative nausea and vomiting (PONV) is a 'big little' problem
      especially after laparoscopic surgeries. Palanosetron is a new potent 5 hydroxy
      tryptamine 3 antagonists. In this randomized double blind clinical study we
      compared the effects of i.v. ondansetron and palanosetron administered at the end
      of surgery in preventing post-operative nausea and vomiting in patients
      undergoing laparoscopic cholecystectomy under general anesthesia. MATERIALS AND
      METHODS: A total of 100 subjects between 18-60 years with Apfel score >=2, were
      randomly assigned into one of the two groups, containing 50 patients each. Group
      A received ondansetron 4 mg i.v. and Group B received palanosetron 0.07 5mg i.v.
      both as bolus before induction. The incidence of nausea, retching and vomiting,
      incidence of total PONV, requirement of rescue antiemetics and adverse effects
      were evaluated during the first 24 h following end of surgery. RESULTS: The
      incidence of nausea was significantly lower in patients who had received
      palanosetron (16%) as compared to ondansetron (24%). Need of rescue antiemetics
      was significantly higher in patients receiving ondansetron (32%) as compared to
      palanosetron (16%). The incidence of total PONV was also significantly lower in
      group receiving palanosetron (20%) as compared to ondansetron (50%). Among the
      side effects, headache was noted significantly higher with ondansetron (20%) as
      compared to palanosetron (6%). CONCLUSION: Palanosetron has got better anti
      nausea effect, less need of rescue antiemetics, favourable side effect profile
      and a decrease in the incidence of total PONV as compared to ondansetron in 24 h
      post operative period in patients undergoing laproscopic cholecystectomy under
      general anesthesia.

PMID- 26195879
TI  - Review of various liver retraction techniques in single incision laparoscopic
      surgery for the exposure of hiatus.
AB  - BACKGROUND: The main aspect of concern for upper GI procedures has been the
      retraction of the liver especially large left lobes as commonly encountered in
      Bariatric surgery. Not doing so would compromise the view of the hiatus, hence
      theoretically reducing the quality of the surgery and increasing the possibility
      of complications. The aim of this study was to review the various liver
      retraction techniques in single incision surgery being done at our institute and
      analyze them. MATERIAL AND METHODS: A retrospective study of the various
      techniques and a subsequent analysis was made based on advantages and
      disadvantages of each method. Objectively a quantitative measure of hiatal
      exposure was done using a scoring system based on the grade of exposure after
      reviewing the surgical videos. From January 2011 to January 2013 total 104
      patients underwent single incision surgery with the various liver retraction
      techniques with following grades of exposure -liver suspension tube technique
      with naso gastric tubing (2.11) and with corrugated drain (2.09) needlescopic
      method (1.2), Umbilical tape sling (1.95), crural stitch method (2.5).
      Needeloscopic method has the best grade of exposure and is the easiest to start
      with. The average time to create the liver retraction was 2.8 to 8.6 min.There
      was no procedure related morbidity or mortality. CONCLUSIONS: The mentioned liver
      retraction techniques are cost effective and easy to learn. We recommend using
      these techniques to have a good exposure of hiatus, without compromising the
      safety of surgery in single incision surgery.

PMID- 26195880
TI  - Achalasia 5 years following Roux-en-y gastric bypass.
AB  - Oesophageal achalasia is a rare, but serious condition in which the motility of
      the lower oesophageal sphincter (LES) is inhibited. This disorder of idiopathic
      aetiology complicates the peristaltic function and relaxation of the LES that may
      cause symptoms such as dysphagia, epigastric pain, and regurgitation of an
      obstructed food. The following case describes achalasia in a patient 5 years
      following a laparoscopic Roux-en-Y gastric bypass (RYGB). The patient underwent a
      laparoscopic Heller myotomy without a fundoplication. Although achalasia seems to
      be a rare occurrence in obese patients, this is the third case documented in a
      patient who previously had an RYGB. The role of performing a fundoplication in
      these patients remains to be elucidated. 

PMID- 26195881
TI  - Intraoperative identification of adrenal-renal fusion.
AB  - Adrenal - renal fusion is a rare entity defined as incomplete encapsulation of
      the adrenal gland and kidney with histologically adjacent functional tissue. This
      report describes the first published intraoperative identification of this
      anomaly during laparoscopic adrenalectomy. The patient was a 59-year-old man with
      chronic hypertension refractory to multiple antihypertensives found to be caused
      by a right-sided aldosterone-producing adrenal adenoma in the setting of
      bilateral adrenal hyperplasia. During laparoscopic adrenalectomy, the normal
      avascular plane between the kidney and adrenal gland was absent. Pathologic
      evaluation confirmed adrenal - renal fusion without adrenal heterotopia.
      Identified intraoperatively, this may be misdiagnosed as invasive malignancy, and
      thus awareness of this anomaly may help prevent unnecessarily morbid resection. 

PMID- 26195883
TI  - Laparoscopic resection for rectal cancer and cholecystectomy for patient with
      situs inversus totalis.
AB  - Situs inversus totalis (SIT) is a rare congenital anomaly presenting with
      complete transposition of thoracic and abdominal viscera. Laparoscopic surgery
      for either rectal cancer or gallbladder diseases with SIT is rarely reported in
      the literature. A 39-year-old woman was admitted to hospital owing to rectal
      cancer. She was diagnosed with SIT by performing radiography and abdominal
      computed tomography scan as a routine preoperative investigation. We performed
      laparoscopic resection for rectal cancer successfully in spite of technical
      difficulties caused by abnormal anatomy. One year later, she was diagnosed with
      cholecysticpolyp, and we performed laparoscopic cholecystectomy for her
      uneventfully. With this case, we believe that performance by an experienced
      laparoscopic surgeon, either laparoscopic resection for rectal cancer or
      cholecystectomy with SIT is safe and feasible. 

PMID- 26195882
TI  - Retrieval of a self-expanding metal stent after migration and incorporation in
      the omental bursa, using a gastroscopic-transgastric laparoscopic rendezvous
      technique.
AB  - Endoscopic drainage is a widely used treatment for pancreatic pseudocysts.
      Drainage-related complications may be related directly to the procedure or may
      occur later as stents migrate or erode into adjacent structures. Migration of a
      self-expanding metal stent into peritoneal cavity and incorporation in the
      omental bursa is rare. When endoscopic retrieval fails a combined laparoscopic
      endoscopic (rendezvous technique) approach offers an alternative to open surgery.
      We report a case of successful gastroscopic-transgastric laparoscopic removal of
      a stent that was dislocated into the omental bursa after a 1/2 year observation
      period. 

PMID- 26195884
TI  - Laparoscopic management of transverse testicular ectopia with persistent
      mullerian duct syndrome.
AB  - A 4-month-old male child presented with right undescended testis and left
      inguinal hernia with funiculitis. Ultrasonography showed funiculitis on the left
      side testis along with presence of 1.5 * 1 cm testis like structure just above
      left testis and empty right scrotal sac without any evidence of mullerian
      structures. On diagnostic laparoscopy, right testicular vessels were crossing
      from right to left and had uterus with both testes in left hernia sac.
      Mobilization of vessels, division of uterus, and hernia repair was done
      laparoscopically. On the review of literature, there is only one case report of
      total laparoscopic repair of transversetesticular ectopia (TTE) with hernia
      without persistent mullerian duct (PMDS). The uniqueness of our case is that it
      had TTE with hernia and PMDS, which were totally managed by laparoscopy. On 6
      months of follow-up, both the testes are palpable in scrotum. 

PMID- 26195885
TI  - Paravesical gossypiboma following inguinal herniorrhaphy: Laparoscopic retrieval.
AB  - Retained surgical sponge (gossypiboma) following an inguinal herniorrhaphy is a
      rare condition and may cause medicolegal problems. Differential diagnosis for the
      lesion should be made meticulously. We report a case of a 45-year-old man who had
      a herniorrhaphy about 8 years previously. He presented one episode of painless
      gross hematuria. Laboratory and imaging studies excluded any significant lesion
      in the urological organs. Abdominal CT scan demonstrated a heterogeneous neoplasm
      of 4 cm in size in the left paravesical area that was retrieved laparoscopically.
      Abdominal CT and clinical suspicion are helpful for diagnosis. Laparoscopy may be
      used to confirm the diagnosis and to remove the retained surgical gauze, and
      considered as an alternative therapy for some selected patients. 

PMID- 26195886
TI  - Laparoscopic restorative proctocolectomy ileal pouch anal anastomosis: How I do
      it?
AB  - Surgery for ulcerative colitis is a major and complex colorectal surgery.
      Laparoscopy benefits these patients with better outcomes in context of cosmesis,
      pain and early recovery, especially in young patients. For surgeons, it is a
      better tool for improving vision and magnification in deep cavities. This is not
      the simple extension of the laparoscopy training. Starting from preoperative
      preparation to post operative care there are wide variations as compared to open
      surgery. There are also many variations in steps of laparoscopic surgery. It
      involves left colon, right colon and rectal mobilisation, low division of rectum,
      pouch creation and anastomosis of pouch to rectum. Over many years after
      standardisation of this technique, it takes same operative time as open surgery
      at our centre. So we present our standardized technique of laparoscopic assisted
      restorative proctocolectomy and ileal pouch anal anastomosis (IPAA). 

PMID- 26195888
TI  - Hypoxia is no hype: Perspectives across Phylogeny, Stem Cell differentiation &
      Geochemistry.

PMID- 26195889
TI  - Intricacies of Pluripotency.
AB  - Pluripotent stem cells have the potential to differentiate into 200 odd cell
      types present in adult body. Pluripotent stem cells available for regenerative
      medicine include embryonic stem (ES) cells, induced pluripotent stem (iPS) cells
      and very small ES-like stem (VSELs) cells. Nuclear OCT-4 is one of the crucial
      factors that dictate pluripotent state. Compared to ES/iPS cells grown in Petri
      dish, VSELs exist in adult body organs and results are emerging to suggest that
      they may have better potential to regenerate adult organs. This is because of
      their distinct epigenetic status as they are closer to the primordial germ cells
      from the epiblast-stage embryo compared to inner cell mass from which ES cells
      are obtained in vitro. We need to make special efforts to study them as they are
      very small in size and tend to get lost during processing. VSELs exist in adult
      organs, get mobilized in response to stress, undergo asymmetric cell divisions to
      give rise to tissue specific progenitors which further differentiate into various
      cell types and are possibly better candidates for regenerative medicine because
      they have no associated risk of tumor formation or immunological rejection. They
      are possibly also the 'embryonic remnants' in adult organs responsible for
      initiating cancer. Thus, rather than not accepting VSELs because they neither
      form teratoma nor divide in vitro like ES cells, it is time that scientific
      community should think of revising the definition of the term 'pluripotency'. 

PMID- 26195890
TI  - Tendinopathies and platelet-rich plasma (PRP): from pre-clinical experiments to
      therapeutic use.
AB  - OBJECTIVES: The restorative properties of platelets, through the local release of
      growth factors, are used in various medical areas. This article reviews
      fundamental and clinical research relating to platelet-rich plasma applied to
      tendinous lesions. MATERIALS AND METHOD: Articles in French and English,
      published between 1 January 2012 and 31 December 2014. dealing with PRP and
      tendons were searched for using the Medline and Scopus data bases. RESULTS: Forty
      seven articles were identified which addressed pre-clinical and clinical studies:
      27 relating to in vitro and in vivo animal studies and 20 relating to human
      studies. Of these, five addressed lateral epicondylitis, two addressed rotator
      cuff tendinopathies, ten dealt with patellar tendinopathies and three looked at
      Achilles tendinopathies. CONCLUSIONS: The majority of pre-clinical studies show
      that PRP stimulates the tendon's healing process. However, clinical series remain
      more controversial and level 1, controlled, randomised studies are still needed.

PMID- 26195891
TI  - Human mesenchymal stem cells stimulate EaHy926 endothelial cell migration:
      combined proteomic and in vitro analysis of the influence of donor-donor
      variability.
AB  - Mesenchymal stem cells (MSCs) stimulate angiogenesis within a wound environment
      and this effect is mediated through paracrine interactions with the endothelial
      cells present. Here we report that human MSC-conditioned medium (n=3 donors)
      significantly increased EaHy-926 endothelial cell adhesion and cell migration,
      but that this stimulatory effect was markedly donor-dependent. MALDI-TOF/TOF mass
      spectrometry demonstrated that whilst collagen type I and fibronectin were
      secreted by all of the MSC cultures, the small leucine rich proteoglycan, decorin
      was secreted only by the MSC culture that was least effective upon EaHy-926
      cells. These individual extracellular matrix components were then tested as
      culture substrata. EaHy-926 cell adherence was greatest on fibronectin-coated
      surfaces with least adherence on decorin-coated surfaces. Scratch wound assays
      were used to examine cell migration. EaHy-926 cell scratch wound closure was
      quickest on substrates of fibronectin and slowest on decorin. However, EaHy-926
      cell migration was stimulated by the addition of MSC-conditioned medium
      irrespective of the types of culture substrates. These data suggest that whilst
      the MSC secretome may generally be considered angiogenic, the composition of the
      secretome is variable and this variation probably contributes to donor-donor
      differences in activity. Hence, screening and optimizing MSC secretomes will
      improve the clinical effectiveness of pro-angiogenic MSC-based therapies. 

PMID- 26195892
TI  - The effects of short-term hypoxia on human mesenchymal stem cell proliferation,
      viability and p16(INK4A) mRNA expression: Investigation using a simple hypoxic
      culture system with a deoxidizing agent.
AB  - A hypoxic environment is thought to be important for the maintenance of stemness
      and suppressing cell senescence, in stem cells. Therefore, a hypoxic condition is
      induced during cell expansion and/or induction of intended differentiation.
      However, the induction of these conditions requires a specially equipped hypoxia
      chamber and expensive gas mixtures, which are expensive and space-consuming.
      Owing to these restrictions, appropriate hypoxic conditions cannot be provided
      during cell transportation, which is increasingly required for regenerative
      medicine. Hence, a simple and economical culture system is required. The purpose
      of this study was to investigate the effects of short-term hypoxic conditions on
      human mesenchymal stem cell (MSC) proliferation, viability, and senescence,
      utilizing the CulturePal system (CulturePal-Zero and CulturePal-Five), a novel
      and simple hypoxic culture system with a built-in deoxidizing agent. The O2
      concentration in the CulturePal-Zero was observed to reduce to <0.1% within 1 h,
      and to 5% within 24h in the CulturePal-Five system. Cell proliferation under
      these hypoxic conditions showed a sharp increase at 5% O2 concentration, and no
      noticeable cell death was observed even at severe hypoxic conditions (<0.1% O2)
      up to 72h. The p16(INK4A) (cell senescence marker) mRNA expression was retained
      under hypoxic conditions up to 72h, but it was up-regulated under normoxic
      conditions. Interestingly, the p16(INK4A) expression altered proportionately to
      the O2 concentration. These results indicated that the short-term hypoxic
      condition, at an approximate O2 concentration of 5%, would be suitable for
      promoting cell proliferation and repressing cell senescence, without aggravating
      the MSC viability. Therefore, the CulturePal systems may be suitable for
      providing an appropriate hypoxic condition in stem cell research and
      transportation. 

PMID- 26195893
TI  - Depleting medicinal plant resources: A threat for survival of Ayurveda.

PMID- 26195894
TI  - Exploring insights towards definition and laws of health in Ayurveda: Global
      health perspective.
AB  - The current healthcare system is focused on disease management. Our current
      approach to treatment begins only after the diagnosis, and then attempts to treat
      the symptoms and prevent the progression. Despite increased global healthcare
      spending, there has been an increasing incidence, and severity of diseases
      pointing to impaired health of the populace. This progressive deterioration in
      general health has created an unsustainable increase in healthcare costs that has
      hampered the economy. Much of the rising costs in healthcare are secondary to
      treating the progression of preventable diseases and focus on creating new
      treatments. There has been an ongoing discussion of incorporating a "defense" or
      prevention as part of our health system. However, there are few established
      guidelines beyond tactical use of vaccination in known infectious diseases and
      screening for chronic diseases and cancers. Ayurveda has the core competency and
      strategy for prevention of disease. Sushruta has propounded the laws of health,
      which are unknown to the current healthcare system. This article describes these
      laws and strategic combination of Ayurveda (defense) and modern medicine
      (offense) to create a complete healthcare system. This system is called
      Symbiohealth and is potentially more effective, less expensive, less toxic and
      creates a healthier society. 

PMID- 26195895
TI  - Concept of Sukha (comfort) mentioned in Dhatusarata (tissue excellence) w.s.r. to
      vocational guidance.
AB  - Agni (digestive fire), Prakruti (constitution), Dhatusarata (tissue excellence),
      Dosha (bio-energies) are the specialties of Ayurveda on which diagnosis,
      treatment and research are based. The description of Dhatusarata (tissue
      excellence) has been given under Dashavidha Pariksha (tenfold examination) in
      Charak Samhita, Viman Sthana, 8(th) chapter. Some qualities, which are mentioned
      in Dhatusarata are difficult to assess, e.g. Sukha, Aishwarya, Upabhoga, Bala,
      etc., There is a need to develop some quantitative parameters to measure these
      qualities according to tissue excellence i.e. Dhatusarata. By assessing Dhatu
      Sarata, one can judge the true strength of a particular Dhatu but only the
      ability or strength is not enough to get success; the liking or interest is also
      essential to achieve success. The purpose of this study is to elaborate the
      concept of Dhatusarata and reveal different aspects of Sukha according to the
      quality of that particular Dhatu in context of vocational guidance. It will help
      to establish interrelationship between Dhatusarata and vocational guidance. It
      will be assessed whether this Sukha quality is merely happiness or having
      different shades according to the excellence of Dhatus and whether this study is
      useful in guiding the person to choose appropriate profession, which will be
      according to his liking and ability. It has been concluded that shades of Sukha
      quality varies with particular Dhatusaras, which may be helpful in guiding a
      suitable profession to an individual which will be according to his ability and
      liking i.e. Sukha for intimate success. 

PMID- 26195896
TI  - A critical appraisal on Swarnaprashana in children.
AB  - Administration of processed gold in children is a unique practice mentioned in
      Ayurveda as "Swarnaprashana" by Acharya Kashyapa thousands of years back. He
      explained evidently the administration of Swarna (gold) in children for the
      benefits of improving intellect, digestion and metabolism, physical strength,
      immunity, complexion, fertility, and life span. There are various formulations of
      gold and even along with herbal drugs explained by different Acharya for
      prolonged usage in children. Swarnaprashana in children can be mainly implicated
      in two contexts of Ayurveda; Lehana (supplementary feeds) and Jatakarma Samskara
      (newborn care). This review is an effort to critically evaluate the available
      data, which may be helpful in clearing some of the existing fallacies on the
      topic. The age and method of administration, benefits and dosage as per various
      classical textbooks of Ayurveda are discussed here along with the reports of
      related scientific studies. This review proposes that the benefits of
      Swarnaprashana can be achieved at multiple levels like as a general health
      promoter and in specific to enhancement of intelligence, digestion, metabolism,
      immunity, physical strength, complexion, or fertility. Ayurveda recommends only
      purified and processed form of gold for internal administration. The age at which
      Swarnaprashana should be administered and its duration can be determined
      depending upon the desired effect in children as a positive health care program. 

PMID- 26195897
TI  - Contribution of Ayurveda in foundation of basic tenets of bioethics.
AB  - Ethics deal with the set of principles of right conduct. The four basic
      principles of bioethics - autonomy, beneficence, non-maleficence and justice are
      known as "principlism". Though these four principles are influenced by the
      western world; in the medical field they are adapted as universal ethics.
      Originally, Ayurveda, the Indian medical system, has strongly advocated ethical
      code of conduct for physicians, but does not get its due recognition till this
      date. Proposed article aims to compare universally accepted basic tenets of
      bioethics and ancient Ayurvedic ethics. For this purpose classical texts of
      Ayurveda and literature regarding principlism was collected and analyzed
      thoroughly. It was found that the essence of ethics is very well-defined and
      described in the fundamental texts of Ayurveda in the form of Sadvritta,
      Chatushpada, Yogya, Vaidyavritti and Aachara Rasayana. Hence, Ayurveda should be
      considered as a trailblazer in establishing the basic tenets of bioethics. 

PMID- 26195898
TI  - Medical geography in Charaka Samhita.
AB  - Charaka Samhita is the oldest and the most authentic treatise on Ayurveda and is
      the ancient medical science of India. Apart from giving information on medical
      conditions and their treatment; it also gives valuable information on
      geographical, social, and economic conditions of India. This article is an
      attempt to explore geographical conditions of the ancient India, its geographical
      position in present India and its medical significance. 

PMID- 26195899
TI  - Management of Madhumeha Janya Upadrava with special reference to diabetic
      nephropathy - A clinical study.
AB  - BACKGROUND: Diabetic nephropathy (DN) is a microvascular complication of diabetes
      mellitus. As the disease DN manifests secondary to Madhumeha, the disease is
      termed as Madhumeha Janya Upadrava. The diagnosis of DN is microalbuminuria is a
      powerful screening tool in screening DN earlier stages. A diabetic can develop
      nondiabetic renal disease like anyone, but the finding of diabetic retinopathy
      strongly suggests that any proteinuria is due to diabetic glomerulosclerosis. In
      this dissertation, all diabetic patients who showed positive diabetic retinopathy
      changes; were screened for 24 h microalbuminuria, at its earlier asymptomatic
      period itself. This research work is specially intended to instigate effective
      therapies at earlier stage itself, thereby prevent further progression. AIM: To
      evaluate the combined effect of Shilajitvadi Vataka, Punarnavadi Mandura,
      Triphala Guggulu and Pippalimooladi Paneeya added with Amrita and Bringaraja in
      DN. MATERIALS AND METHODS: Single blind clinical study with pre-test and post
      test was designed. The study conducted on 15 patients of both sex aged between 20
      and 80 years, having DN changes through assays for microalbuminuria and other
      biochemical assays; along with prior confirmation of diabetic retinopathy
      changes. The duration of the study was 48 days and patients were assessed on
      every 15 days. RESULTS: After 48 days of treatment, statistically significant
      improvement in levels of microalbuminuria with mean difference 83.76 MUg/24 h,
      highly significant improvement in status of Agni and statistically no significant
      improvement in glomerular filtration rate by 2.381 mL/min/1.73m(2). No
      significant side-effects were observed. CONCLUSION: Overall the study showed
      encouraging results in treating the malady DN.

PMID- 26195900
TI  - Comparative clinical efficacy of Ashtangavaleha and Vyaghreehareetakee Avaleha on
      Tamaka Shwasa (bronchial asthma) in children.
AB  - BACKGROUND: Tamaka Shwasa is a chronic inflammatory condition of the lung airways
      resulting in episodic airflow obstruction. This disease is more predominant in
      children and aged population. Apart from being the leading cause of
      hospitalization for children, it is one of the most important chronic conditions
      causing elementary school absenteeism. The parallel disease entity in
      contemporary medical science to this disorder is Bronchial Asthma. AIM: This
      study was aimed to evaluate the clinical efficacy of Ashtangavaleha and
      Vyaghreehareetakee Avaleha on Tamaka Shwasa (Bronchial Asthma) in Children.
      MATERIALS AND METHODS: The study was therapeutic interventional randomized
      clinical trial. Totally 100 patients suffering from Tamaka Shwasa were selected,
      and 74 patients completed the course of treatment. Patients were divided into two
      groups. Ashtangavaleha was administered in group AG and Vyaghreehareetakee
      Avaleha was administerd in group VG (5-15g in divided doses) for 8 weeks
      duration. Comaprative assesment of both the drugs was done on the signs and
      symptoms of the disease, pulmonary function test and quality of life parameters.
      RESULTS: When the individualized overall effect of therapy was considered, more
      number of patients treated with Ashtangavaleha reached moderate improvement zone
      than the patients treated with Vyaghreehareetakee Avaleha. CONCLUSIONS: The trial
      showed a marginal better efficacy of Ashtangavaleha (66.66%) in comparison to
      Vyaghreehareetakee Avaleha (63.15%) on the overall condition of the patients even
      though the superiority was statistically insignificant (>0.05).

PMID- 26195901
TI  - Clinical assessment of dietary interventions and lifestyle modifications in
      Madhumeha (type- 2 Diabetes Mellitus).
AB  - BACKGROUND: India leads the world with maximum number of diabetes patients being
      termed as the "diabetes capital of the world." Certain risk factors including
      unsatisfactory diet, overweight, and a sedentary lifestyle are potentially
      reversible. Acharayas have widely described the role of diet and activities to
      control Madhumeha (type 2 diabetes mellitus [T2DM]) along with medications.
      Habitual consumption of roasted or dry Barley (Hordeum vulgare L.) flour, Mudga
      (Phaseolus aureus Roxb.) and Amalaki (Emblica officinalis Gaertn.) prevents the
      manifestation of Prameha. AIM: To assess the clinical effects of dietary
      interventions and life style modifications in Madhumeha patients. MATERIALS AND
      METHODS: Present study was carried out on 56 patients of Madhumeha from S.S.
      Hospital, Banaras Hindu University, Varanasi. Dietary interventions and life
      style modifications schedule was prepared based on Ayurvedic principles and
      patients were advised to follow this regimen. Three consecutive follow-ups were
      done for 3 months at the interval of one month each. RESULTS: Significant
      improvement was observed in clinical signs and symptoms along with plasma glucose
      and glycosylated hemoglobin (HbA1c) in Madhumeha patients after these
      interventions (P < 0.001). CONCLUSION: Dietary interventions and life style
      modifications are two important tools by which adequate glycemic control can be
      obtained, especially in newly diagnosed T2DM patients and in patients who are on
      antidiabetic medication, but not properly controlled.

PMID- 26195902
TI  - Effect of Neem oil and Haridra on non-healing wounds.
AB  - BACKGROUND: In Ayurveda, Vrana (wound) has stated as tissue destruction and
      discoloration of viable tissue due to various etiology. In Sushruta Samhita,
      Sushruta described Vrana as a main subject. Most commonly Vrana can be classified
      into Shuddha and Dushta Vrana (chronic wound/nonhealing ulcers). Among the
      various drugs mentioned for Dushta Vrana, two of them, Neem (Azadirechta indica
      A. Juss) oil and Haridra (Curcuma longa Linn.) powder are selected for their wide
      spectrum action on wound. AIM: To compare the effect of Neem oil and Haridra in
      the treatment of chronic non-healing wounds. MATERIALS AND METHODS: Total 60
      patients of wounds with more than 6 weeks duration were enrolled and
      alternatively allocated to Group I (topical application of Neem oil), Group II
      (Haridra powder capsules, 1 g 3 times orally) and Group III (both drugs).
      Duration of treatment was considered until complete healing of the wound, whereas
      4(th) and 8(th) week were considered for assessment of 50% healing. Wound size
      was measured and recorded at weekly intervals. Wound biopsy was repeated after 4
      weeks for assessment of angiogenesis and deoxyribonucleic acid (DNA) analysis.
      RESULTS: After 8 weeks of treatment, 50% wound healing was observed in 43.80%
      patients of Group I, 18.20% patients of Group II, and 70.00% patients of Group
      III. Microscopic angiogenesis grading system scores and DNA concentration showed
      highly significant effect of combined use of both drugs when compared before and
      after results of treatment (P < 0.001). CONCLUSION: Topical use of Neem oil and
      oral use of Haridra powder capsule used in combination were found effective for
      chronic non-healing wounds.

PMID- 26195903
TI  - A clinical study on the Naimittika Rasayana effect of Silajatu and Mamajjaka in
      type-2 Diabetes Mellitus.
AB  - BACKGROUND: Recent years have shown an alarming rise in the incidence of diabetes
      mellitus (DM) all over the world. The present management of DM it not
      satisfactory. Hence, alternative systems of medicine are also being explored.
      Prameha as described in Ayurveda is a disease synonymous with today's DM. The
      patients of Prameha inherently carry the risk of impaired Agni and depleted Ojas
      status, that is, hypometabolic and immuno-compromised state. Now the primary goal
      is not merely to achieve normoglycemia, but also to minimize its complications.
      In this context, many Ayurvedic drugs are undergoing extensive research. AIM: To
      evaluate the anti-diabetic, immune-enhancer and biofire balancing effects of
      Naimittika Rasayana drugs viz. Silajatu and Mamajjaka in type-2 DM. MATERIALS AND
      METHODS: A total of 95 patients of type-2 DM were registered; in which 84
      patients turned up for full follow-up. Patients were randomly allocated into
      three groups; Group-A was treated with Mamajjaka (500mg twice a day) and Group-B
      with Silajatu (500mg twice a day) and Group-C was treated with modern drug and
      assessment was done at monthly intervals for three months. RESULTS: The selected
      Rasayana drugs have shown good response on subjective and objective parameters.
      The Mamajjaka treated patients responded better. However, as regards the
      reduction of post prandial blood sugar, Silajatu was superior. CONCLUSION: The
      Ayurveda-inspired holistic approach seems to have a unique response promoting
      Agni (biofire) and Ojas (immune strength) status leading to good health and
      wellness.

PMID- 26195904
TI  - Effect of Sri Lankan traditional medicine and Ayurveda on Sandhigata Vata
      (osteoarthritis of knee joint).
AB  - Reported case was a 63-year-old female with end-stage osteoarthritis (OA)
      (Sandhigata Vata) of the left knee joint accompanied by exostoses. Radiology (X
      ray) report confirmed it as a Kellgren-Lawrence grade III or less with exostoses.
      At the beginning, the Knee Society Rating System scores of pain, movement and
      stability were poor, and function score was fair. Srilankan traditional and
      Ayurveda medicine treatment was given in three regimens for 70 days. After 70
      days, external treatment of oleation and 2 capsules of Shallaki (Boswellia
      serrata Triana and Planch) and two tablets of Jeewya (comprised of Emblica
      officinalis Gaertn., Tinospora cordifolia [Willd.] Millers. and Terminalia
      chebula Retz.), twice daily were continued over 5 months. Visual analogue scale
      for pain, knee scores in the Knee Society online rating system and a Ayurveda
      clinical assessment criteria was used to evaluate the effects of treatments in
      weekly basis. After treatment for 70 days, the Knee Society Rating System scores
      of pain, movement and stability were also improved up to good level and function
      score was improved up to excellent level. During the follow-up period, joint
      symptoms and signs and the knee scores were unchanged. In conclusion, this OA
      patient's quality of life was improved by the combined treatment of Sri Lankan
      traditional medicine and Ayurveda. 

PMID- 26195905
TI  - Pharmacognostical and high performance thin layer chromatography studies on
      leaves of Clerodendrum infortunatum L.
AB  - BACKGROUND: Clerodendrum infortunatum L. commonly known as Bhant plays a
      significant role in Indian System of Medicine, that is, Ayurveda, due to its
      medicinal properties. It grows easily in waste places of all areas of India,
      Bangladesh, and Myanmar. AIM: The present study was carried out with a view to
      lay down its pharmacognostic standards along with high-performance thin layer
      chromatography (HPTLC) studies in order to document/validate its therapeutic
      benefits. MATERIALS AND METHODS: In this research, leaves of C. infortunatum were
      subjected to pharmacognostic evaluation parameters such as macroscopy,
      quantitative microscopy, physicochemical studies, phytochemical screening. HPTLC
      has been developed for detection and quantification of gallic acid and tyrosine
      in C. infortunatum. Increasing serial dilutions of reference standard gallic acid
      (20-100 MUg/mL) and tyrosine (20-100 MUg/mL) were scanned at 254 nm and 280 nm,
      respectively. RESULTS: Microscopy of leaf revealed the presence of anisocytic
      stomata, sclereids, glandular and covering trichome, and prisms of calcium
      oxalate crystal. The total ash, water-soluble, and acid insoluble ash values of
      leaves were 9.95%, 2.15%, and 0.70%, respectively. The maximum extractive value
      of crude powder was in the water. HPTLC studies revealed that the amount of
      gallic acid in the crude powder of test sample were high (0.244 mg/g) in
      comparison to tyrosine (0.081 mg/g). CONCLUSION: The data generated would be of
      significant use for the authentication of drug and would also serve as a
      reference for the standardization and quality control of C. infortunatum.

PMID- 26195906
TI  - Antioxidant potential and its relationship with polyphenol content and degree of
      polymerization in Opuntia elatior Mill. fruits.
AB  - BACKGROUND: Opuntia elatior Mill. (Nagaphani) fruits are traditionally
      recommended as an expectorant, remedy for whooping cough, asthma, gonorrhea,
      ulcers, tumors, in the treatment of diarrhea and syphilis. Many of these diseases
      are allied with oxidative stress caused by free radicals. Thus, current research
      is directed towards finding naturally-occurring antioxidants of plant origin.
      AIM: To evaluate antioxidant potential of hydro-alcoholic extract of the O.
      elatior fruits (HAOE) and its fractions. MATERIALS AND METHODS: Using 1,1
      diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide radical scavenging assay, total
      polyphenolic, flavonoid (FA), flavanone (FO) contents and degree of
      polymerization in relation with its antioxidant activity were examined. RESULTS:
      The experimental data indicated that the HAOE, ethyl acetate (EAOE) and butanol
      (BFOE) soluble fractions have shown significant antioxidant activity. The highest
      polyphenolic, FA, FO contents and degree of polymerization were found in EAOE.
      The scavenging potential was in the order of Ascorbic Acid > EAOE > BFOE > HAOE >
      BIOE, where ascorbic acid was used as a positive control. The increased
      antioxidant potential of EAOE and BFOE fractions over HAOE extract may be
      attributed to the purification achieved by fractionation of the extract which in
      turn resulted in an increase in the degree of polymerization and segregation of
      secondary metabolites. CONCLUSION: The fruit of O. elatior can be used as the
      best alternative for synthetic antioxidants.

PMID- 26195907
TI  - Standard manufacturing procedure of Shadguna Balijarita Makaradhwaja.
AB  - BACKGROUND: Makaradhwaja is one of the most potent herbomineral medicines of
      Ayurveda. Different references for the preparation of Makaradhwaja were reported
      in classics. According to the proportion of sulfur (Gandhaka), three references
      were mentioned in classics that is, Dwiguna (2:1 = S: Hg), Triguna (3:1 = S: Hg)
      and Shadguna (6:1 = S: Hg). Makaradhwaja is prepared by Kupipakwa system of
      heating. In the preparation of Kupipakwa medicine as the ratio of sulfur to
      mercury increases it becomes difficult to prepare medicine. AIM: To standardize
      manufacturing procedure of Shadguna Balijarita Makaradhwaja (SBM). MATERIALS AND
      METHODS: Total four batches of SBM were prepared by using electrical muffle
      furnace (EMF). All the involved procedures were followed as per classical
      guidelines. RESULTS: Average 13.68% yield of SBM was observed. CONCLUSION: SBM
      requires intermittent heating pattern, that is, mild heat (100-125 degrees  C)
      for 2.5 hrs, moderate heat (250-450 degrees  C) for 4.5 hrs and strong heat (450
      600 degrees  C) for 5 hrs for 290.5 g Kajjali.

PMID- 26195908
TI  - Evaluation of acute toxicity and anti-ulcerogenic study of rhizome starch of two
      source plants of Tugaksheeree (Curcuma angustifolia Roxb. and Maranta arundinacea
      Linn.).
AB  - BACKGROUND: Disorders like hyperacidity and gastric ulcers are found very
      frequently now days because of a faulty lifestyle. Starches (Satwa) obtained from
      the rhizomes of two plants namely, Curcuma angustifolia Roxb. (Fam.
      Zingiberaceae) and Maranta arundinacea Linn. (Fam. Marantaceae) are used in
      folklore practice, as Tugaksheeree, for the treatment of the above-mentioned
      complaints. AIM: To assess the acute toxicity potential of the C. angustifolia
      and M. arundinacea along with their assessment for adaptogenic activity, by
      noting their effect on forced swimming-induced hypothermia and gastric ulceration
      in rats. MATERIALS AND METHODS: For acute toxicity study, the effect of test
      drugs C. angustifolia and M. arundinacea rhizome starch were studied after a
      single administration of up to three dose levels, with 4400 mg/kg as the maximum
      dose. The animals were observed for 72 hours periodically and mortality was
      recorded up to seven days. The adaptogenic and anti-ulcer activities were
      assessed by determining and comparing the changes in rectal temperature, ponderal
      changes, ulcer index and histopathological parameters in the test drug group with
      that of stress control group. RESULTS: Both the drugs did not produce any toxic
      symptoms or mortality even up to the maximum dose level of 4400 mg/kg. Both the
      test drugs significantly reversed the stress-induced gastric ulceration in
      comparison to stress-control rats. Starch from rhizome of C. angustifolia
      reversed forced swimming-induced hypothermia apparently, but not to a significant
      extent. However, the reversal of hypothermia found statistically significant in
      the rhizome starch of the M. arundinacea treated group. CONCLUSION: M.
      arundinacea had better anti-stress activity in comparision to C. angustifolia.

PMID- 26195909
TI  - Bioavailability study of calcium sandoz-250 by atomic absorption spectroscopy in
      albino rats.
AB  - BACKGROUND: Calcium sandoz-250 is an Ayurvedic calcium supplement, containing
      Khatika Churna. Bioavailability study of the formulation is essential for
      estimation of peak plasma concentration (C max), time to C max and rate of
      absorption. AIM: To evaluate the absorption parameters of calcium sandoz-250 in
      albino rats by atomic absorption spectroscopic (AAS) method. MATERIALS AND
      METHODS: Study was carried out as a single dose, open-label, randomized study.
      Estimation of calcium was carried out by AAS, after validating the method for a
      few parameters for the estimation. Pharmacokinetic parameters such as C max, time
      to peak concentration (T max), area under the plasma concentration - time curve
      were calculated for calcium on administration of calcium sandoz-250. RESULTS:
      Linearity curve was plotted for 0.5-2.5 ppm, given R (2) value 0.9975. The C max,
      i.e. C max after administration of calcium sandoz-250 was 0.793 mg/ml at 90 min
      (T max). Measurable calcium-blood levels were noticed in all subjects up to 3.0 h
      after administration of calcium sandoz-250. CONCLUSION: Calcium sandoz-250,
      consisting of Khatika Churna, increases the blood calcium level in albino rats.

PMID- 26195910
TI  - Dolichos biflorus Linn. ameliorates diabetic complications in streptozotocin
      induced diabetic rats.
AB  - BACKGROUND: Horsegram (Dolichos biflorus Linn.) is a known antilithiatic,
      hypolipedemic and has free radical scavenging activity and increased production
      of reactive oxygen species play a role in pathophysiological mechanisms that
      trigger diabetic complications. AIM: To see the effect of daily oral feeding of
      D.biflorous on nephropathy and retinopathy in streptozotocin (STZ) induced
      diabetic rats. MATERIALS AND METHODS: A total of 24 healthy rats were randomly
      grouped into controls, diabetic and diabetic on Dolichos. Diabetes was induced by
      a single dose of STZ (55 mg/kg) and animals were given prepared food and water ad
      libitum. Dolichos was orally given at 300 mg/kg/day to rats in diabetic on
      Dolichos group for next 30 days. Fasting blood glucose levels was monitored at
      beginning and at the end of the experiment while assessment of serum creatinine
      levels and histopathological study of kidney and retina was carried only at the
      end of the experiment. Statistical differences between groups were analyzed using
      analysis of variance followed by, Bonferroni test as posthoc test. RESULTS:
      Results indicated improvement in serum creatinine levels and reduced glomerular
      sclerosing and Bowman's space with interstitial alterations and significantly
      reduced renal hypertrophy in diabetic rat son Dolichos diabetic rats (P < 0.001).
      Retinal layers showed inconsistent improvement in the width of the neuronal
      layers and decreased vacuolization of plexiform layers and retinal vessel
      density. CONCLUSION: D. biflorus at doses of 300 mg/kg/day for 30 days resulted
      in gradual but significant decreased diabetic nephropathy.

PMID- 26195911
TI  - Use of Curcuma longa L. extract to stain various tissue samples for histological
      studies.
AB  - BACKGROUND: Curcuma longa L. is a perennial herb and a member of the
      Zingiberaceae (ginger) family, which is used extensively in foods as well as in
      Ayurvedic and Chinese systems of medicine. Current researches have focused on its
      antioxidant, hepatoprotective, anti-inflammatory, anticarcinogenic and
      antimicrobial properties. Until now, very few studies suggested its role as a
      histological stain. AIM: To ascertain its efficacy to be used as a counterstain
      after hematoxylin, to compare it's staining ability with that of routinely used
      eosin dye and also to ascertain its role in various collagen diseases. MATERIALS
      AND METHODS: Turmeric rhizomes were cut into small pieces and were dried. These
      dried turmeric rhizomes were milled to form fine powder, which was then processed
      to form dye for staining tissue structures. RESULTS: It revealed that turmeric
      can be used as a counterstain after hematoxylin, its staining ability was also
      good and comparable to that of eosin dye with a special affinity for collagen and
      muscle fibers. CONCLUSION: Turmeric dye can be used as a histological stain,
      which stains similar to eosin dye and its specific affinity for collagen and
      muscle fibers authenticates its role in the treatment of collagen and muscle
      disorders.

PMID- 26195912
TI  - Evaluation of polyherbal formulation (SJT-HT-03) for antihypertensive activity in
      albino rats.
AB  - BACKGROUND: Hypertension is an incurable pathological condition and lifelong
      therapy is required. Long term use of conventional synthetic anti-hypertensive
      drugs is associated with a spectrum of toxic effects. However, therapeutic
      interventions using herbal drugs for hypertension have gained considerable
      attention worldwide. AIM: To evaluate the anti-hypertensive activity of
      polyherbal formulation (SJT-HT-03). MATERIALS AND METHODS: The polyherbal
      formulation (SJT-HT-03) comprises of leaves of Aegle marmelos L., fruits of
      Benincasa hispida Thunb., Garcinia indica Thouars, and flowers of Musa
      paradiasica L., Rosa indica L., Hibiscus rosa sinensis L. Selected plants as
      mentioned above were collected, dried and extracted with different solvents.
      Formulation SJT-HT-03 (250 mg/kg, p.o.), was evaluated using two kidney one clip
      (2K1C) model and deoxycorticosterone acetate (DOCA)-salt-induced hypertension
      model using the enalapril (10 mg/kg, p.o.) and hydrochlorothiazide (5 mg/kg,
      p.o.) as a reference standard drug in respective models. RESULTS: SJT-HT-03
      significantly reduced (P < 0.001, one-way analysis of variance followed by
      Turkey's multiple comparison tests) systolic as well as diastolic blood pressure
      (BP) in 2K1C and DOCA-salt model. Further, SJT-HT-03 has shown a significant
      reduction (P < 0.01) in angiotensin converting enzyme (ACE) activity in serum,
      clipped kidney as well as in lungs in 2K1C model, whereas significant reduction
      (P < 0.05) in serum Na(+) and increase in serum K(+) level in DOCA model.
      CONCLUSION: Polyherbal formulation SJT-HT-03 possess significant anti
      hypertensive activity by producing direct depressant effect on heart, inhibition
      of ACE, aldosterone antagonistic as well as diuretic effect and thereby act on
      multiple targets to achieve optimal effect.

PMID- 26195913
TI  - Evaluation of analgesic activity of Terminalia arjuna (Roxb.) Wight and Arn bark:
      A tribal claim.
AB  - BACKGROUND: Plants occupy an important place in folk medicine all over the world
      for centuries and indigenous communities have developed their own specific
      knowledge on plant resources, uses, management, and conservation. Research
      interest and activities in the area of ethno medicine have increased tremendously
      in the last decade. Currently, scientists are evincing keen interest in the
      scientific evaluation of ethno medical claims. Bark powder of Arjuna (Terminalia
      arjuna [Roxb.] Wight and Arn) is used by tribals for the management of some
      painful conditions. AIM: To evaluate analgesic activity of T. arjuna bark in
      rodents. MATERIALS AND METHODS: For evaluation of analgesic activity, different
      experimental models, that is, the acetic acid-induced writhing syndrome in mice,
      formaldehyde-induced paw licking response and tail flick test in rats were
      designed. Experiments were carried out at two-dose levels, that is,
      therapeutically equivalent dose (TED) and TED * 2. Animals were divided into
      three groups (six animals in each group), first group serving as a control group,
      second and third group labeled as test drug group. RESULTS: Test drug at both the
      doses significantly decreased the writhing syndrome in comparison to control the
      group. In comparison to control the group, incidences of formalin-induced paw
      licking were reduced in test drug groups in both early and late phases of pain.
      In tail flick response, threshold was significantly increased in both test drug
      groups at every time intervals. CONCLUSION: Study showed that stem bark of T.
      arjuna possesses analgesic activity in all experimental models.

PMID- 26195914
TI  - Management of spastic cerebral palsy through multiple Ayurveda treatment
      modalities.
AB  - BACKGROUND: Cerebral palsy (CP) is a leading cause of childhood disability
      affecting function and development. The global incidence of CP is 2:1000. It has
      been reported that children with CP and their caretaker have impaired health
      related quality of life (QOL). Of the many types and subtypes of CP, none has any
      known cure. For a detailed description of the disease CP, though, there is no one
      to one correlation in Ayurvedic classics; it can be taken as Vata Vyadhi as far
      as its etiology and symptomatology are concerned. AIM: To assess the effect of
      certain Panchakarma procedures in the management of CP. MATERIALS AND METHODS:
      Total 8 patients were registered and treated with 5 days of Udvartana, 5 days of
      Abhyanga followed by Sarvanga Swedana and then 8 days of Yoga Basti. The same
      course of treatment has been repeated for 3 times with an interval of 14 days.
      Ashtanga Ghrita was given during whole procedures as internal medication. Results
      of treatment were assessed with anthropometrical measurement, developmental
      milestone, Modified Ashworth Scale, spasm scale, reflex scale, and muscle power
      grading. RESULT: This Ayurvedic management shows good result in CP patients,
      especially by improving growth (height, weight, chest circumference) and
      development (head holding and sitting), reducing spasticity of left upper limb
      and muscle spasm. CONCLUSION: Multisystem approach is needed to improve the
      condition of the patient. Panchakarma along with internal medication should be
      given to improve all the facets of spastic CP. Yoga Basti acts by their own mode
      of action and can be used freely for such disease conditions.

PMID- 26195915
TI  - A preliminary physicochemical evaluation of Darvyadi Yoni Varti: A compound
      Ayurvedic formulation.
AB  - BACKGROUND: Darvyadi Yoni Varti is an Ayurvedic formulation indicated for the
      management of Garbhasaya Grivamukhagata Vrana (cervical erosion). Though a number
      of drugs are available in modern medicine, interest towards Ayurveda is gaining.
      Drugs with Vranasodhana, Ropana and Prasadana properties like Sphatika, Darvi,
      Haridra, and Lodhra are useful in this situation and are selected to prepare Yoni
      Varti. AIM: To standardize and evaluate preliminary pharmacognostical as well as
      physicochemical profiles of Darvyadi Yoni Varti. MATERIALS AND METHODS: Raw
      material was analyzed in the Pharmacognostical Laboratory for genuinity before
      converting into Varti. Finished product was analyzed by following pharmacopoeial
      standards. RESULTS: The pH value of Darvyadi Yoni Varti was 5.0, water soluble
      extract was 23.3%w/w, alcohol soluble extract was 8.7%w/w, ash value was
      5.16%w/w, loss on drying was 71.73%w/w. High performance thin layer
      chromatography was carried out; in which maximum 10 spots at 254 nm and 3 spots
      at 366 nm were distinguished. CONCLUSION: Pharmacognostical study of raw drug
      revealed the quality and genuineness of all the constituents of Darvyadi Yoni
      Varti.

PMID- 26195916
TI  - Using implicit attitudes of exercise importance to predict explicit exercise
      dependence symptoms and exercise behaviors.
AB  - OBJECTIVES: "Fast" (i.e., implicit) processing is relatively automatic; "slow"
      (i.e., explicit) processing is relatively controlled and can override automatic
      processing. These different processing types often produce different responses
      that uniquely predict behaviors. In the present study, we tested if explicit,
      self-reported symptoms of exercise dependence and an implicit association of
      exercise as important predicted exercise behaviors and change in problematic
      exercise attitudes. DESIGN: We assessed implicit attitudes of exercise importance
      and self-reported symptoms of exercise dependence at Time 1. Participants
      reported daily exercise behaviors for approximately one month, and then completed
      a Time 2 assessment of self-reported exercise dependence symptoms. METHOD:
      Undergraduate males and females (Time 1, N = 93; Time 2, N = 74) tracked daily
      exercise behaviors for one month and completed an Implicit Association Test
      assessing implicit exercise importance and subscales of the Exercise Dependence
      Questionnaire (EDQ) assessing exercise dependence symptoms. RESULTS: Implicit
      attitudes of exercise importance and Time 1 EDQ scores predicted Time 2 EDQ
      scores. Further, implicit exercise importance and Time 1 EDQ scores predicted
      daily exercise intensity while Time 1 EDQ scores predicted the amount of days
      exercised. CONCLUSION: Implicit and explicit processing appear to uniquely
      predict exercise behaviors and attitudes. Given that different implicit and
      explicit processes may drive certain exercise factors (e.g., intensity and
      frequency, respectively), these behaviors may contribute to different aspects of
      exercise dependence.

PMID- 26195917
TI  - Delving Beyond Conscious Attitudes: Validation of an Innovative Tool for
      Assessing Parental Implicit Attitudes toward Physical Punishment.
AB  - Parenting scholars have long been interested in understanding the prevalence,
      determinants, and child outcomes associated with the use of physical discipline.
      To date, much of the empirical research in this area has utilized self-report
      measures to assess this construct. However, the subjective nature of
      participants' explicit reports presents an important confound to studying this
      issue. Thus, the overarching aim of this study was to provide the first test of
      an implicit assessment of physical discipline through using a Go/No-go
      Association Task (GNAT). A GNAT-Physical Discipline was developed and examined in
      two separate studies of mothers and their 2-3 year old child. One study was
      conducted in an online format and the second within a laboratory design. Across
      both studies, findings suggested that the GNAT-Physical Discipline distinguished
      between positive and negative implicit attitudes towards the use of physical
      discipline. In addition, negative implicit attitudes were uniquely linked to
      maternal reports of physical discipline when compared to other discipline
      practices. Results suggest the potential for the GNAT paradigm in research on
      parental attitudes around the use of physical discipline in parenting contexts.
      In addition, our use of an online format (with implicit assessments of key
      constructs) demonstrates that child and family researchers may be able to explore
      their hypotheses in larger, geographically diverse samples.

PMID- 26195918
TI  - An Interactive Cluster Heat Map to Visualize and Explore Multidimensional
      Metabolomic Data.
AB  - Heat maps are a commonly used visualization tool for metabolomic data where the
      relative abundance of ions detected in each sample is represented with color
      intensity. A limitation of applying heat maps to global metabolomic data,
      however, is the large number of ions that have to be displayed and the lack of
      information provided about important metabolomic parameters such as m/z and
      retention time. Here we address these challenges by introducing the interactive
      cluster heat map in the data-processing software XCMS Online. XCMS Online
      (xcmsonline.scripps.edu) is a cloud-based informatic platform designed to
      process, statistically evaluate, and visualize mass-spectrometry based
      metabolomic data. An interactive heat map is provided for all data processed by
      XCMS Online. The heat map is clickable, allowing users to zoom and explore
      specific metabolite metadata (EICs, Box-and-whisker plots, mass spectra) that are
      linked to the METLIN metabolite database. The utility of the XCMS interactive
      heat map is demonstrated on metabolomic data set generated from different
      anatomical regions of the mouse brain.

PMID- 26195919
TI  - Self-criticism of physicians, patient participation and risk competence.
AB  - Self-criticism of physicians and patient participation are the pillars of modern
      medical ethics and medical programmes. Patients expect risk minimisation from
      physicians, mostly without realising how much they could actively do themselves
      in this respect. But what about the willingness of German people to take risks,
      how high is it really at present? Direct empirical data are not available, but
      results from general empirical research show that people's willingness to take
      risks is probably rather low. Post-heroic societies of welfare states are less
      likely to take risks than supposedly heroic ones. Therefore, the question whether
      it is responsible for medical experts to transfer even more responsibility to non
      medical laypeople becomes increasingly important in a social context. 

PMID- 26195920
TI  - Chances and risks in medical risk communication.
AB  - Communication between physicians and patients in everyday life is marked by a
      number of disruptive factors. Apart from specific interests, mistakes, and
      misunderstandings on both sides, there are main factors that contribute to the
      risk in risk communication. Using the example of mammography screening, the
      current work demonstrates how the meaning of test results and the informative
      value of measures taken to reduce risk are often misunderstood. Finally, the
      current work provides examples of successful risk communication. 

PMID- 26195921
TI  - Societal perspectives on risk awareness and risk competence.
AB  - Medical risks can be assessed by objectifiable therapeutic features; however,
      these risks are also characterised to a considerable degree by individual and
      social values. People tend to strive towards both freedom as well as safety; in a
      medical context, these two aims are taken into account by shared decision-making
      models and by stricter regulations in the pharmaceutical sector. Media reports on
      medical risks are caught between providing information and economic interests,
      and this conflict particularly complicates rational discussions about unexpected
      risks (for instance, in the field of natural medicine). Thus, it is necessary to
      create the type of information culture which allows differentiating between real
      and less pronounced risks. 

PMID- 26195922
TI  - Risks, risk assessment and risk competence in toxicology.
AB  - Understanding the toxic effects of xenobiotics requires sound knowledge of
      physiology and biochemistry. The often described lack of understanding
      pharmacology/toxicology is therefore primarily caused by the general absence of
      the necessary fundamental knowledge. Since toxic effects depend on exposure (or
      dosage) assessing the risks arising from toxic substances also requires
      quantitative reasoning. Typically public discussions nearly always neglect
      quantitative aspects and laypersons tend to disregard dose-effect-relationships.
      One of the main reasons for such disregard is the fact that exposures often occur
      at extremely low concentrations that can only be perceived intellectually but not
      by the human senses. However, thresholds in the low exposure range are often
      scientifically disputed. At the same time, ignorance towards known dangers is
      wide-spread. Thus, enhancing the risk competence of laypersons will have to be
      initially restricted to increasing the awareness of existing problems. 

PMID- 26195923
TI  - Media influence on risk competence in self-medication and self-treatment.
AB  - Media play an important role in the reception of health risks; thus, media
      competence is important for enhancing the risk competence of patients and
      consumers. In addition to life-long health education, risk competence
      particularly requires careful handling of health information because, at present,
      the key problem is not the lack of sufficient information on health topics but
      the quality of such information. Patients and consumers of health procedures and
      health products also require information which relates to their daily life and
      matches their life style. 

PMID- 26195924
TI  - Evidence-based health information and risk competence.
AB  - Consumers and patients want to be included in decisions regarding their own
      health and have an ethically justified claim on informed decisions. Therefore,
      sound information is required, but health information is often misleading and
      based on different interests. The risks of disease and the benefits of medical
      interventions tend to be overestimated, whereas harm is often underestimated.
      Evidence-based health information has to fulfil certain criteria, for instance,
      it should be evidence-based, independent, complete, true as well as
      understandable. The aim of a medical intervention has to be explained. The
      different therapeutic options including the option not to intervene have to be
      delineated. The probabilities for success, lack of success and unwanted side
      effects have to be communicated in a numerical and understandable manner.
      Patients have the right to reject medical interventions without any sanctions. 

PMID- 26195925
TI  - Increasing the risk competence of patients: an interdisciplinary task.

PMID- 26195926
TI  - Developing and piloting a multifactorial intervention to address participation
      and quality of life in nursing home residents with joint contractures
      (JointConImprove): study protocol.
AB  - BACKGROUND: Joint contractures are common problems in frail older people in
      nursing homes. Irrespective of the exact extent of older individuals in geriatric
      care settings living with joint contractures, they appear to be a relevant
      problem. Also, the new emphasis on the syndrome of joint contractures, e. g. by
      the German statutory long term care insurance, led to an increase in assessment
      and documentation efforts and preventive interventions in clinical care. However,
      more attention should be paid to the actual situation of older individuals in
      nursing homes with prevalent joint contractures, particularly their experience of
      related activity limitations and participation restrictions. Thus, the aim of
      this study is 1) to develop a tailored intervention to improve functioning, and
      especially participation and quality of life in older residents with joint
      contractures in nursing homes and 2) to test the feasibility of the intervention
      accompanied by a rigorous process evaluation. METHODS: The complex intervention,
      which will be developed in this project follows the UK Medical Research Council
      (MRC) framework and integrates the perspectives of all potentially relevant user
      groups, from the affected individuals to clinicians and researchers. The
      development process will comprise a systematic literature review, reanalysis of
      existing data and the integration of the knowledge of the affected individuals
      and experts. The developed intervention including a comprehensive process
      evaluation will be pilot tested with residents with joint contractures in three
      nursing homes. DISCUSSION: The projected study will provide a tailored
      intervention to improve functioning, participation and quality of life in older
      residents with joint contractures in nursing homes. With this focus, the
      intervention will support patient relevant outcomes. The pilot study including
      process evaluation will offer a first opportunity to indicate the size of the
      intervention's effect and prepare further studies.

PMID- 26195927
TI  - Influence of Pre-Storage Irradiation on the Oxidative Stress Markers, Membrane
      Integrity, Size and Shape of the Cold Stored Red Blood Cells.
AB  - BACKGROUND: To investigate the extent of oxidative damage and changes in
      morphology of manually isolated red blood cells (RBCs) from whole blood, cold
      stored (up to 20 days) in polystyrene tubes and subjected to pre-storage
      irradiation (50 Gy) and to compare the properties of SAGM-preserved RBCs stored
      under experimental conditions (polystyrene tubes) with RBCs from standard blood
      bag storage. METHODS: The percentage of hemolysis as well as the extracellular
      activity of LDH, thiobarbituric acid-reactive substances, reduced glutathione
      (GSH), and total antioxidant capacity (TAC) were measured. Changes in the
      topology of RBC membrane, shape, and size were evaluated by flow cytometry and
      judged against microscopy images. RESULTS: Irradiation caused significant LDH
      release as well as increased hemolysis and lipid peroxidation, GSH depletion, and
      reduction of TAC. Prolonged storage of irradiated RBCs resulted in
      phosphatidylserine exposure on the cell surface. By day 20, approximately 60% of
      RBCs displayed non-discoid shape. We did not notice significant differences in
      percentage of altered cells and cell volume between RBCs exposed to irradiation
      and those not exposed. CONCLUSION: Irradiation of RBC transfusion units with a
      dose of 50 Gy should be avoided. For research purposes such as studying the role
      of antioxidants, storage of small volumes of RBCs derived from the same donor
      would be more useful, cheaper, and blood-saving.

PMID- 26195928
TI  - Differences in Rat and Human Erythrocytes Following Blood Component
      Manufacturing: The Effect of Additive Solutions.
AB  - BACKGROUND: Small animal models have been previously used in transfusion medicine
      studies to evaluate the safety of blood transfusion products. Although there are
      multiple studies on the effects of blood banking practices on human red blood
      cells (RBCs), little is known about the effect of blood component manufacturing
      on the quality of rat RBCs. METHODS: Blood from Sprague-Dawley rats and human
      volunteers (n = 6) was collected in CPD anticoagulant, resuspended in SAGM or
      AS3, and leukoreduced. In vitro quality was analyzed, including deformability,
      aggregation, microvesiculation, phosphatidylserine (PS) expression, percent
      hemolysis, ATP, 2,3-DPG, osmotic fragility, and potassium concentrations.
      RESULTS: Compared to human RBCs, rat RBCs had decreased deformability, membrane
      rigidity, aggregability, and microvesiculation after component manufacturing
      process. Rat RBCs in SAGM showed higher hemolysis compared to human RBCs in SAGM
      (rat 4.70 +/- 0.83% vs. human 0.34 +/- 0.07%; p = 0.002). Rat RBCs in AS3 had
      greater deformability and rigidity than in SAGM. The number of microparticles/ul
      and the percentage PS expression were lower in rat RBCs in AS3 than in rat RBCs
      in SAGM. Hemolysis was also significantly lower in AS3 compared to SAGM (2.21 +/-
      0.68% vs. 0.87 +/- 0.39%; p = 0.028). CONCLUSION: Rat RBCs significantly differ
      from human RBCs in metabolic and membrane-related aspects. SAGM, which is
      commonly used for human RBC banking, causes high hemolysis and is not compatible
      with rat RBCs.

PMID- 26195929
TI  - Introducing Pathogen Reduction Technology in Poland: A Cost-Utility Analysis.
AB  - BACKGROUND: Mirasol(r) pathogen reduction technology (PRT) uses UV light and
      riboflavin to chemically inactivate pathogens and white blood cells in blood
      components. In the EU, Mirasol PRT is CE-marked for both plasma and platelet
      treatment. In Poland, the decision to introduce PRT treatment of the national
      supply of fresh frozen plasma has spurred interest in evaluating the cost
      effectiveness of this strategy. METHODS: A decision-analytic model evaluated the
      incremental costs and benefits of introducing PRT to the existing blood safety
      protocols in Poland. RESULTS: Addition of PRT treatment of plasma to current
      screening in Poland is estimated to cost 2.595 million PLN per quality-adjusted
      life year (QALY) (610,000 EUR/QALY); treating both plasma and platelet components
      in addition to current safety interventions had a lower cost of 1.480 million
      PLN/QALY (348,000 EUR/QALY). CONCLUSIONS: The results suggest that in Poland the
      cost per QALY of PRT is high albeit lower than found in previous economic
      analyses of PRT and nucleic acid testing in North America. Treating both
      platelets and plasma components is more cost-effective than treating plasma
      alone. Wide confidence intervals indicate high uncertainty; to improve the
      precision of the health economic evaluation of PRT, additional hemovigilance data
      are needed.

PMID- 26195930
TI  - Treatment of Platelet Concentrates with the Mirasol Pathogen Inactivation System
      Modulates Platelet Oxidative Stress and NF-kappaB Activation.
AB  - BACKGROUND: Pathogen inactivation (PI) technologies for platelets aim to improve
      transfusion safety by preventing the replication of contaminating pathogens.
      However, as a consequence of treatment, aspects of the platelet storage lesion
      are amplified. Mirasol treatment also affects platelet signal transduction and
      apoptotic protein expression. The aim of this study was to examine the effect of
      Mirasol treatment on the generation of reactive oxygen species (ROS) and
      subsequent oxidative stress. METHODS: Pooled platelet concentrates were prepared
      in platelet-additive solution (70% SSP+ / 30% plasma). ABO-matched platelets were
      pooled and split, and treated with the Mirasol system (TerumoBCT) or left
      untreated as a control. Platelet samples were tested on day 1, 5, and 7 post
      collection. RESULTS: Mirasol-treated platelets had increased formation of ROS by
      day 5 of storage. Oxidative damage, in the form of protein carbonylation, was
      higher in Mirasol-treated platelets, whilst no effect on nitrotyrosine formation
      or lipid peroxidation was detected. The NF-kappaB signaling pathway was also
      activated in Mirasol-treated platelets, with increased expression and
      phosphorylation of NF-kappaB p65 and IkappaBalpha. CONCLUSION: These data
      demonstrate that Mirasol-treated platelets produce more ROS and display protein
      alterations consistent with oxidative damage.

PMID- 26195931
TI  - Determining the Effect of Preparation and Storage: An Effort to Streamline
      Platelet Components as a Source of Growth Factors for Clinical Application.
AB  - BACKGROUND: In the present study, different methods for preparation of platelet
      rich plasma (PRP) are investigated in order to standardize the component in terms
      of growth factor content. The effects of concentration technique and storage
      duration are also analyzed. METHODS: PRP was collected from 40 donors by
      plateletpheresis as well as by the buffy coat and tube method. Concentration of
      growth factors was performed using double freeze thaw- and CaCl2-induced
      degranulation techniques. Growth factor estimation was performed using ELISA.
      RESULTS: The levels of growth factors were highest in PRP from buffy coat,
      moderately lower in plasma gained by plateletpheresis and lowest in that obtained
      by the tube method. Mean levels of platelet-derived growth factors (PDGF) AB and
      BB are significantly higher when CaCl2 was used for concentrating the growth
      factors. The mean levels of transforming growth factor beta1 and insulin-like
      growth factor I were higher when applying the double freeze thaw technique. There
      was a substantial decline in the levels of growth factors during storage.
      CONCLUSION: The buffy coat method is suitable as preparation method for PRP in
      most settings. The double freeze thaw technique is better suited as concentration
      technique as it causes lysis of both platelets and white blood cells for
      releasing growth factors and is easier to perform. Growth factors are not stable
      in plasma, thus PRP should be frozen immediately after preparation.

PMID- 26195932
TI  - Donor Hemovigilance with Blood Donation.
AB  - BACKGROUND: Reports on unexpected events (UEs) during blood donation (BD)
      inadequately consider the role of technical UEs. METHODS: Defined local and
      systemic UEs were graded by severity; technical UEs were not graded. On January
      1, 2008, E.B.P.S.-Logistics (EBPS) installed the UE module for plasma management
      software (PMS). Donor room physicians entered UEs daily into PMS. Medical
      directors reviewed entries quarterly. EBPS compiled data on donors, donations,
      and UEs from January 1, 2008 to June 30, 2011. RESULTS: 6,605 UEs were observed
      during 166,650 BDs from 57,622 donors for a corrected incidence of 4.30% (0.66%
      local, 1.59% systemic, 2.04% technical UEs). 2.96% of BDs were accompanied by one
      UE and 0.45% by >1 UE (2-4). 6.3% of donors donating blood for their first time,
      3.5% of those giving blood for their second time, and 1.9% of donors giving their
      third or more BD experienced UEs. Most common UEs were: discontinued collections
      due to venous access problems, repeated venipuncture, and small hematomas. Severe
      circulatory UEs occurred at a rate of 16 per 100,000 BDs. CONCLUSIONS: Technical
      UEs were common during BD. UEs accompanied first and second donations
      significantly more often than subsequent donations.

PMID- 26195933
TI  - Advanced Therapy Medicinal Products: How to Bring Cell-Based Medicinal Products
      Successfully to the Market - Report from the CAT-DGTI-GSCN Workshop at the DGTI
      Annual Meeting 2014.
AB  - On September 11, 2014, a workshop entitled 'Advanced Therapy Medicinal Products:
      How to Bring Cell-Based Medicinal Product Successfully to the Market' was held at
      the 47th annual meeting of the German Society for Transfusion Medicine and
      Immunohematology (DGTI), co-organised by the European Medicines Agency (EMA) and
      the DGTI in collaboration with the German Stem Cell Network (GSCN). The workshop
      brought together over 160 participants from academia, hospitals, small- or medium
      sized enterprise developers and regulators. At the workshop, speakers from EMA,
      the Committee for Advanced Therapies (CAT), industry and academia addressed the
      regulatory aspects of development and authorisation of advanced therapy medicinal
      products (ATMPs), classification of ATMPs and considerations on cell-based
      therapies for cardiac repair. The open forum discussion session allowed for a
      direct interaction between ATMP developers and the speakers from EMA and CAT. 

PMID- 26195934
TI  - Alleviating the Breast Cancer Experience: A Plea for Psycho-Oncology.

PMID- 26195935
TI  - Psychosocial Care for Cancer Patients.

PMID- 26195936
TI  - For the Benefit of Others: Reasons Why Women with Breast Cancer Participate in
      RCTs.
AB  - BACKGROUND: Appreciation of the barriers and drivers affecting enrolment in
      randomised clinical trials (RCTs) is important for future trial design,
      communication and information provision. METHODS: As part of an intervention to
      facilitate UK multidisciplinary team communication about RCTs, women with breast
      cancer who discussed trials with doctors or research nurses completed
      questionnaires examining i) clarity of trial information and ii) reasons for
      their trial decision. RESULTS: 152 women completed the questionnaires; 113/152
      (74%) consented to RCT enrolment. Patients' satisfaction with communication about
      the trial information was very good, irrespective of participation decisions.
      Acceptors' and decliners' responses to 9/16 statements concerning decisions about
      trial participation differed significantly. 'Wanting to help with doctor's
      research' influenced 100% acceptors compared to 57% of decliners (p < 0.001).
      Decliners were more likely to be 'worried about randomisation' (20 vs. 39%; p <
      0.035) and to 'want doctor to choose treatment rather than be randomised' (31 vs.
      53%; p < 0.031). Primary reason for trial acceptance was altruism; 'I feel that
      others with my illness will benefit from the results of the trial', 58/108 (54%).
      CONCLUSION: A majority of women accepted RCT entry citing altruistic motivations
      as the primary driver for participation. Trial design and setting (metastatic or
      adjuvant) had little impact on participation.

PMID- 26195937
TI  - Breast Cancer Patients' Fear of Treatment: Results from the Multicenter
      Longitudinal Study BRENDA II.
AB  - BACKGROUND: Fear of cancer treatment can become overwhelming. It is important to
      understand what patients are mainly afraid of and what factors are correlated
      with intense fear of treatment. METHODS: Patients with primary breast cancer (n =
      761) completed questionnaires about fear of treatment before surgery (t1), and
      before (t2) and after (t3) adjuvant treatment. Psychological comorbidity was
      assessed using the Patient Health Questionnaire. Logistic regression identified
      predictors of intense fear of treatment. RESULTS: Patients were most afraid of
      chemotherapy (mean score 3.5), and fear remained high throughout follow-up; fear
      of radiotherapy and of surgery was lower and decreased over time (from 2.7 to
      2.2, p < 0.0001; and from 2.6 to 2.2, p < 0.0001, respectively). Patients with
      psychological co-morbidity (odds ratios (OR) 1.7-3.0) and those who had heard
      reports of negative experiences with cancer treatments from others (OR 3.8-16.2)
      were more likely to have intense fear of all the treatments. Patients with a
      previous cancer less often expressed fear of surgery (OR 0.6, 95% confidence
      interval 0.4-1.0). CONCLUSION: Fear of treatment, especially of chemotherapy, is
      prevalent in many patients with primary breast cancer. Patients with
      psychological co-morbidity and those who have heard reports of negative
      experiences with cancer treatment are at higher risk of experiencing intense
      fear.

PMID- 26195938
TI  - Intimate Relationships Affected by Breast Cancer: Interventions for Couples.
AB  - A cancer diagnosis imposes significant emotional distress on a substantial
      proportion of patients and their partners, posing many challenges for both
      members of a couple. Facing a breast cancer diagnosis, couples may experience
      psychosocial distress, which might also affect their individual and dyadic
      functioning. Coping with cancer from a couple-based perspective as a dyadic
      stressor can profoundly influence psychosocial adjustment as well as individual
      and dyadic functioning of patients and spouses. Dyadic coping allows a better
      matching of needs, sharing of worries, and mutual support, resulting in higher
      relationship satisfaction. The aim of this article is to provide an overview of
      the issues faced by women diagnosed with breast cancer and their spouses, with
      particular emphasis on interventions for couples coping with cancer. The
      effectiveness of couple-based interventions is summarized with a critical
      discussion. For further research, a better understanding of the challenges
      couples coping with cancer may face and more insights on how to improve
      interventions for couples might facilitate improvements in the quality of cancer
      care. 

PMID- 26195939
TI  - Hyperthermia Is Now Included in the NCCN Clinical Practice Guidelines for Breast
      Cancer Recurrences: An Analysis of Existing Data.
AB  - BACKGROUND: Hyperthermia has been included in the 2013 National Comprehensive
      Cancer Network (NCCN) guidelines as an option for the treatment of breast
      recurrences. The purpose of this article is to demonstrate the important role of
      hyperthermia as a therapeutic modality by presenting clinical trials on this
      subject carried out in the last decades. MATERIALS AND METHODS: All relevant
      trials published since 1987 were retrieved from Medline and reviewed. RESULTS:
      Results show that the addition of hyperthermia to radiotherapy and/or
      chemotherapy for the treatment of breast cancer enhances treatment response and
      can increase local control. CONCLUSION: Further studies are required to evaluate
      potential benefits of hyperthermia in the treatment of other kinds of superficial
      tumors.

PMID- 26195940
TI  - Application of a 70-Gene Expression Profile to Japanese Breast Cancer Patients.
AB  - BACKGROUND: As data on using MammaPrint(r), a 70-gene expression profile for
      molecular subtyping of breast cancer, are limited in Japanese patients, we aimed
      to determine the gene profiles of Japanese patients using MammaPrint and to
      investigate its possible clinical application for selecting adjuvant treatments.
      PATIENTS AND METHODS: 50 women treated surgically at our institution were
      examined. The MammaPrint results were compared with the St Gallen 2007 and
      intrinsic subtype risk categorizations. RESULTS: Of 38 cases judged to be at
      intermediate risk based on the St Gallen 2007 Consensus, 11 (29%) were in the
      high-risk group based on MammaPrint. 1 of the 30 luminal A-like tumors (3%) was
      judged as high risk based on MammaPrint results, whereas 7 of the 20 tumors (35%)
      categorized as luminal B-like or triple negative were in the low-risk group.
      There have been no recurrences to date in the MammaPrint group, and this is
      possibly attributable to most of the high-risk patients receiving chemotherapy
      that had been recommended on the basis of their MammaPrint results. CONCLUSIONS:
      Our results indicate that MammaPrint is applicable to Japanese patients and that
      it is of potential value in current clinical practice for devising individualized
      treatments.

PMID- 26195941
TI  - St. Gallen/Vienna 2015: A Brief Summary of the Consensus Discussion.
AB  - The 2015 St. Gallen Consensus Conference on early breast cancer took place in
      Vienna, Austria, for the first time. After 3 days of high-level presentations by
      international panel members of clinical trials having been reported recently in
      the field, the traditional Saturday voting tried to translate the assembled
      knowledge into clinical treatment recommendations intended to guide clinical
      practice of breast cancer care for the 'average' patient. This report summarizes
      the results of the 2015 international panel voting procedures with respect to
      locoregional and endocrine treatment, chemotherapy, targeted therapy, as well as
      adjuvant bisphosphonate use. This report is not aimed to replace the official St.
      Gallen consensus publication - some recommendations may even be altered in the
      final paper - but should serve as a preliminary rapid report of this important
      meeting. 

PMID- 26195942
TI  - Cardiac Toxicity after Radiotherapy for Breast Cancer: Myths and Facts.
AB  - Radiotherapy is an important component in the multidisciplinary treatment of
      breast cancer. In recent years, the cardiac risks of radiation have been
      discussed several times. This problem has long been known and resolved from the
      radiotherapeutic point of view. The current data is briefly described here. 

PMID- 26195944
TI  - Aromatase Inhibitors in the Prevention of Breast Cancer.

PMID- 26195943
TI  - Breast Cancer and Sarcoidosis: Case Series and Review of the Literature.
AB  - BACKGROUND: Sarcoidosis is a chronic inflammatory disease of unknown etiology,
      which can involve different organs and systems. Accordingly, sarcoidosis can
      mimic breast cancer, making the differential diagnosis very difficult. CASE
      REPORT: 5 patients with a diagnosis of both sarcoidosis and breast cancer
      followed by the Rabin Medical Center between January 1993 and June 2012 were
      enrolled in this study. Additionally, a comprehensive literature review which
      identified 104 patients diagnosed with breast cancer and sarcoidosis was carried
      out. In both populations reviewed, the average age at diagnosis of sarcoidosis
      and breast cancer was 57 years. Among the 66 patients with both sarcoidosis and
      breast cancer, sarcoidosis preceded breast cancer in 31 cases, followed it in 23
      cases, and appeared concurrently in 10 cases. CONCLUSION: Based on our clinical
      cases and literature review, a histological study is recommended over imaging if
      sarcoidosis or breast cancer may be present. Furthermore, breast cancer is rarely
      associated with sarcoidosis or sarcoidosis-like reaction.

PMID- 26195945
TI  - Elective Urological Surgery Following Coronary Stent Implantation: To Whom, How
      To Do It?
AB  - Coronary artery disease is one of the most common diseases today and the primary
      cause of sudden death. The development of atherosclerosis and the incidence of
      symptomatic heart and vascular diseases increase depending on the average life
      expectancy in the elderly population. Stent applications in the treatment of
      coronary artery disease are quite widespread and are a standard procedure. Stent
      applications are applied to approximately 2 million people in the United States
      every year. Therefore, there is an increase in the number of patients with
      stents. This increase is an important and complex situation for patients who are
      planned for urological elective surgery. The necessity of treating the patient
      with the least morbidity and mortality, and supplying the balance in terms of the
      dose and duration of antiplatelet agents which are used for patients with stents
      who are planned for elective urological surgery, is main subject of our review.
      To whom and what should be the treatment are assessed accompanied by the
      literature. 

PMID- 26195947
TI  - The Effect of Bisphosphonates on Bone Mineral Density in Metastatic Prostate
      Cancer Patients Who Are Treated with Anti-Androgen Drugs and Radiotherapy.
AB  - OBJECTIVE: To evaluate the potential effect of bisphosphonates on bone mineral
      density (BMD) in patients who are treated with anti-androgen drugs and
      radiotherapy for metastatic prostate cancer. MATERIALS AND METHODS: The data of
      31 patients with metastatic prostate cancer who were treated with anti-androgen
      drugs and radiotherapy during a 1-year period were retrospectively reviewed.
      Patients were divided in 2 groups, in which 17 patients in group 1 were treated
      with zoledronic acid (4 mg/month, intravenous) and 14 patients in group 2 who did
      not receive zoledronic acid. BMD was measured before the treatment and at the end
      of the 1st year by dual energy X-ray absorptiometry. Statistical analyses were
      performed with the T test. RESULTS: Mean age of the patients was 71.42 +/-
      6.7(range 59-85) years. A significant increase was noted for pelvic bone, femoral
      neck, and lumbar vertebrae t scores when pretreatment and 1st year measurements
      were compared in group 1 (p < 0.05). In group 2 a significant decrease was noted
      for pelvic bone and femoral neck t scores at the end of the 1st year (p < 0.05).
      A significant increase was noted for pelvic bone and femoral neck follow-up in
      BMD values at the end of the 1st year compared to initial measurements in group
      1. A significant decrease was noted for lumbar vertebrae follow-up in BMD values
      at the end of the 1st year when compared to initial values in group 2.
      CONCLUSION: Zoledronic acid significantly increases BMD and delays unfavorable
      outcomes for bones in men who are treated with anti-androgen drugs and
      radiotherapy for metastatic prostate cancer.

PMID- 26195946
TI  - A Prospective Randomised Paired Trial of Sirolimus versus Tacrolimus as Primary
      Immunosuppression following Non-Heart Beating Donor Kidney Transplantation.
AB  - INTRODUCTION: With calcineurin inhibitors potentiating damage from ischaemia
      reperfusion injury in kidneys from donors after cardiac death we wanted to
      investigate the role of substituting sirolimus for tacrolimus in the delayed
      introduction of calcineurin inhibitor regime used in our centre. METHOD: A
      prospective randomised paired open-label study was performed taking pairs of
      kidneys from each donor and randomising one to a tacrolimus-based regime and the
      other to a similar regime based on sirolimus. Graft function at one year was the
      primary endpoint. RESULTS: Total 31 pairs of kidneys were randomised to each
      group, with 19 pairs of recipients available for analysis after post
      randomisation study exclusions. Despite a higher incidence of biopsy proven acute
      rejection in the sirolimus group, renal allograft function was similar in both
      groups at three-monthly intervals up to one year post-transplant. All episodes of
      acute rejection in the sirolimus group occurred in the first three months. Graft
      and patient survival at one year was 100% in the tacrolimus group, with one death
      with functioning graft in the sirolimus group (95% survival). Unfortunately, 10
      of the 19 patients in the sirolimus arm required switch of medication to
      tacrolimus due to acute rejection or intolerable drug side effects. CONCLUSIONS:
      Graft survival and function were very similar in the two groups despite the
      higher rate of acute rejection in the sirolimus arm, raising the possibility that
      the damage done by acute rejection was adequately offset by the nephron-sparing
      effect of sirolimus compared to tacrolimus. Sirolimus may have a role as a longer
      term maintenance immunosuppressant after initial treatment with a different agent
      such as tacrolimus or belatacept.

PMID- 26195948
TI  - Diagnostic and Prognostic Significance of Serum and Tissue Galectin 3 Expression
      in Patients with Carcinoma of the Bladder.
AB  - BACKGROUND: Galectins are group of proteins found in the cytoplasm, nucleus, cell
      surface and extracellular matrix. Galectin 3 (Gal-3) displays pathological
      expression in a variety of processes such as tumorigenesis. PATIENTS AND METHOD:
      70 patients classified into the control group, cystitis group, transitional cell
      carcinoma group, and squamous cell carcinoma group were enrolled in this study
      which aimed to detect the serum level and the intensity of tissue expression of
      Gal-3. RESULTS: Both serum level and tissue expression of Gal-3 were
      statistically higher in bladder cancer patients compared to the other groups. Gal
      3 level expression increased from low to high grade urothelial tumors, with a
      statistically significant increase of its level and expression between muscle
      invasive and non-muscle invasive Ta urothelial tumors. CONCLUSION: The serum Gal
      3 level is sensitive and specific for the diagnosis of bladder cancer. The
      prognostic significance of tissue expression is to be confirmed.

PMID- 26195949
TI  - Use of BioPatch(r) (Protective Disk with Chlorhexidine Gluconate) in Closed
      Suction Drainage for Penile Implant Surgery.
AB  - BACKGROUND: The use of closed-suction drains after penile implant surgery remains
      controversial. The use of BioPatch(r), a protective disk with chlorhexidine
      gluconate, may reduce the incidence of drain-related infections, one of the
      feared complications of drains. The aim of this study is to describe a novel use
      of BioPatch(r) in penile implant surgery as well as additional techniques that
      may potentially minimize infection rates. METHODS: A description of operative
      technique and a review of the literature will be presented. A novel approach to
      penile implant surgery that may reduce infection rates is described. RESULTS: A
      simple technique is described for surgeons considering implementation of closed
      suction drains after penile implant surgery. CONCLUSION: Although randomized
      controlled studies looking at drain placement following penile implant surgery
      are lacking, the addition of BioPatch(r) and the implementation of surgical
      techniques as described are potentially helpful in preventing infection following
      this surgery.

PMID- 26195950
TI  - Epididymal Leiomyoadenomatoid Tumor: A Case Report and Review of Literature.
AB  - Primary tumors of the epididymis are rare. Adenomatoid tumors are benign, usually
      found within the wall of fallopian tubes or beneath the uterine serosa. They are
      most frequently diagnosed as benign tumors of the epididymis and represent 30% of
      paratesticular tumors. The origin of this tumor is mesothelial cells. Leiomyoma
      are less common in the paratesticular localization. The origin of this tumor is
      smooth muscle cells. Clinically, these tumors are indistinctive with a painless
      mass of the scrotum. Here, we reported a case of combined leiomyoadenomatoid
      tumor. The histogenesis of this lesion remains unknown. This entity can be the
      result of a collision of the two tumors, or it can be a subtype of adenomatoid
      tumors with smooth muscle hyperplasia. This case showed the difficulty that
      occurs in the identification of this kind of lesion. Only one case of this entity
      in the epididymis was described in the literature. Leiomyoadenomatoid tumor is a
      benign neoplasm. In our case, this lesion was surgically removed in toto and no
      recurrence was observed. 

PMID- 26195951
TI  - Retraction-Related Acute Liver Failure after Urological Laparoscopic Surgery.
AB  - Liver retraction is necessary for optimal exposure during laparoscopic right
      renal surgery. We described a patient who developed fulminant liver failure as a
      result of liver retractor-induced excessive ischemic changes in the right lobe of
      the liver. A 37-year-old male underwent a right side laparoscopic pyeloplasty for
      ureteropelvic junction obstruction. At the beginning of the operation, a small
      snake retractor was placed through a 5-mm port under direct vision. The liver was
      lifted in the appropriate direction to optimize exposure by using the laparoscope
      holder. The operation was prolonged. However, we achieved significant
      improvements in the efficiency of liver retraction using the holder. On the first
      postoperative day, the patient's serum levels of GOT, GPT and LDH had remarkably
      increased. A computerized tomogram confirmed the presence of excessive ischemic
      changes of the right lobe of the liver. Our method which used a laparoscope
      holder device for liver retraction maintained a better surgical field. However,
      neglecting to make minor adjustments to the positioning of the retractor can
      cause significant pressure on the liver parenchyma in a single area. As surgical
      procedures increase in complexity, the surgeon should keep these potential side
      effects in mind and shift the retraction point at regular intervals. In this
      report, we discussed various types of retractor-related liver injuries and their
      management, and highlighted the importance of intermittent release of retraction
      during prolonged surgery. 

PMID- 26195952
TI  - Perinephric Collection: Hematoma or Duodenal Perforation?
AB  - A 74-year-old man presented with a history of collapse and abdominal pain.
      Initial imaging showed a left sided preirenal collection. The initial working
      diagnosis was perirenal hematoma secondary to renal trauma. Subsequent patient
      deterioration led to further imaging which led to the diagnosis of a duodenal
      perforation with tracking of duodenal contents into the left perirenal space.
      This important differential should be a consideration in cases of perinephric
      collections of unknown etiology. 

PMID- 26195953
TI  - Procidentia as a Cause of Obstructive Uropathy and Acute Kidney Injury.
AB  - Pelvic organ prolapse can affect urinary tract function by reducing flow rates
      and increasing post void residual urine volumes secondary to outlet obstruction.
      If the diagnosis is missed or left untreated, pelvic organ prolapse can lead to
      acute renal injury, chronic renal failure or even end stage renal disease.
      Herein, we present a case of a patient who presented to Albert Einstein Medical
      Center in Philadelphia, PA with urinary retention and acute kidney injury
      secondary to complete uterine prolapse, also referred to as procidentia. 

PMID- 26195954
TI  - Primary Ureteral Lymphoma Presenting with Acute Flank Pain.
AB  - Non-Hodgkin's lymphoma (NHL) represents 4% of newly diagnosed cancer in 2013 with
      a 59-82% 5-year survival depending on the tumor location. Primary presentation of
      lymphoma consists of lymphadenopathy or swelling of the lymph nodes and non
      specific systemic symptoms such as fevers, night sweats, and weight loss. Less
      commonly, NHL arises from non-lymphoid tissue. We report a unique case of NHL
      arising from the ureteral wall which was visualized via non-contrast CT and
      direct vision through ureteroscopy. 

PMID- 26195955
TI  - Undescended Testis Presenting as Incarcerated Inguinal Hernia in Adults: A Rare
      Case and Literature Review.
AB  - Most cases of undescended testis are asymptomatic and diagnosed in the first
      years of life. In some rare cases the diagnosis is established during childhood
      due to sudden torsion of the spermatic cord. Its presence in adults is rare and
      its precipitance of an acute abdomen or incarcerated inguinal hernia as first
      clinical manifestation is seldom described in the literature. In this report, we
      described a case of an elderly male with undescended testis associated with a
      reactive inflammatory mass incarcerated at the superficial inguinal ring. To the
      best of our knowledge, this has not been previously described. 

PMID- 26195956
TI  - Malignant Mesothelioma of the Epididymis: A Case Report.
AB  - Malignant mesothelioma of the epididymis is a very rare tumor. We report a case
      of a 33-year old male with a left hydrocele that presented for evaluation of
      infertility. Scrotal ultrasound revealed a left extratesticular mass. Final
      pathology revealed malignant mesothelioma involving the epididymis, with well
      differentiated epithelioid morphology. Metastatic workup was negative. 

PMID- 26195958
TI  - Clinical Pathology of Bartholin's Glands: A Review of the Literature.
AB  - The Bartholin's glands are located symmetrically at the posterior region of the
      vaginal opening and play an important role in the female reproductive system.
      These two pea-sized glands are involved in mucus secretion and vaginal
      lubrication. Cyst formation in the glands is common and results from mucus build
      up in gland ducts. It is important to monitor such cysts because they may occur
      in the form of carcinomas. Larger cysts and abscesses are found in the lower
      vestibular region and typically present with erythema and edema. Biopsy is an
      effective method for distinguishing between Bartholin's gland cysts and
      differential diagnosis. While smaller cysts may be asymptomatic and may be left
      untreated, larger cysts require medical attention. Several treatment options are
      available, including marsupialization and CO2 laser. Healing and recovery depend
      on the severity of infection and course of treatment. 

PMID- 26195959
TI  - Are Adult Ureteroscopes Safe in the Management of Urolithiasis in a Pediatric
      Population?
AB  - INTRODUCTION: Debate remains regarding the optimal caliber of ureteroscopes in
      the management of pediatric urolithiasis, ranging from pediatric scopes to
      standard scopes. The aim of this study was to assess the safety and efficacy of
      stone management in a pediatric population using standard adult ureteroscopes.
      METHODS: A retrospective review of all ureteroscopic procedures in patients under
      the age of 16 years was carried out. Standard adult 7.5 French semi-rigid and 6
      French flexible ureteroscopes were used. RESULTS: During the study period, 8
      patients underwent 21 ureteroscopic procedures. Two patients had rigid
      ureteroscopy, seven had flexible ureterorenoscopy and one had a subsequent open
      procedure. No patients required ureteric dilation. Double J ureteric stents were
      utilized in 7 patients. There were no complications. All patients required extra
      corporeal shock wave lithotripsy. Stone clearance was achieved in all patients.
      CONCLUSION: Our series demonstrates that, in skilled hands, adult ureteroscopes
      can be use safely for the treatment of urolithiasis in pediatric patients.

PMID- 26195960
TI  - Microsurgical Varicocele Repair on Men with Grade III Lesions and Chronic Dull
      Scrotal Pain: A Pilot Study.
AB  - INTRODUCTION: The aim of the present study was to evaluate the effectiveness of
      microsurgical varicocele repair in patients with grade III lesions and chronic
      dull scrotal pain. MATERIALS AND METHODS: The study was based on 8 patients with
      grade III left-sided varicocele and chronic dull scrotal pain for whom a
      microsurgical subinguinal varicocele repair was performed. The 1-year follow-up
      included pain assessment and scrotal examination. RESULTS: Of the 8 patients, 7
      (88%) reported complete resolution of pain with no palpable varicocele on scrotal
      examination. No cases of testicular atrophy or hydrocele formation were reported.
      CONCLUSION: These results indicated that microsurgical varicocele repair may
      benefit patients with grade III lesions and chronic dull scrotal pain.

PMID- 26195961
TI  - Transrectal Ultrasound Guided Biopsy of the Prostate: Is the Information
      Accessible, Usable, Reliable and Readable?
AB  - BACKGROUND/AIMS: To evaluate the accessibility, usability, reliability and
      readability of Internet information regarding transrectal ultrasound (TRUS)
      guided biopsy of the prostate. MATERIALS AND METHODS: The terms "prostate
      biopsy", "TRUS biopsy" and "transrectal ultrasound guided biopsy of the prostate"
      were separately entered into the each of the top 5 most accessed Internet search
      engines. Websites were evaluated for accessibility, usability and reliability
      using the LIDA tool - a validated tool for the assessment of health related
      websites. Website readability was assessed using the Flesch Reading Ease Score
      and the Flesch Kincaid Grade Level. RESULTS: Following the application of
      exclusion criteria, 82 unique websites were analyzed. There was a significant
      difference in scores depending on authorship categories (p <= 0.001), with health
      related charity websites scoring highest (mean 122.29 +/- 13.98) and non-academic
      affiliated institution websites scoring lowest (mean 87 +/- 19.76). The presence
      of advertisements on a website was associated with a lower mean overall LIDA tool
      score (p = 0.024). Only a single website adhered to the National Institutes for
      Health recommendations on readability. CONCLUSIONS: This study demonstrates
      variability in the quality of information available to Internet users regarding
      TRUS biopsies. Collaboration of website design and clinical acumen are necessary
      to develop appropriate websites for patient benefit.

PMID- 26195962
TI  - Cocaine Use in the Infertile Male Population: A Marker for Conditions Resulting
      in Subfertility.
AB  - INTRODUCTION: We sought to evaluate the incidence and effect of cocaine use in
      the infertile male population. MATERIALS AND METHODS: Men presenting for
      fertility evaluation reporting cocaine usage were identified via prospectively
      collected database. Data were analyzed for usage patterns, reproductive history,
      associated drug use and medical conditions, hormonal and semen parameters.
      RESULTS: Thirty-eight out of 4,400 (0.9%) men reported cocaine use. Most used
      cocaine every 3 months or less. Compared with non-cocaine using men, cocaine
      users reported more recreational drug use (89 vs. 9.2%), marijuana use (78.9 vs.
      11.4%), chlamydia (10.5 vs. 3%), herpes (7.9 vs. 2.5%), and tobacco use (55.3 vs.
      19.5%). After excluding men with causes for azoospermia, the mean semen
      parameters for cocaine users were: volume 2.47 +/- 1.02 ml; concentration 53.55
      +/- 84.04 * 10(6)/ml; motility 15.72 +/- 12.26%; total motile sperm count 76.67
      +/- 180.30 * 10(6). CONCLUSIONS: Few (< 1%) men in our infertile population
      reported the use of cocaine, and the frequency of use was low. Given the low use
      rates and limitations of reporting bias, it is difficult to determine the direct
      effect of cocaine use on male fertility. However, while infrequent cocaine use
      seems to have limited impact on semen parameters, men reporting cocaine use
      represent a different cohort of men than the overall infertile population, with
      higher rates of concurrent substance abuse, tobacco use and infections, all of
      which may negatively impact their fertility. Reported cocaine users should be
      screened for concurrent drug use and infections.

PMID- 26195963
TI  - Efficacy of Duloxetine in the Early Management of Urinary Continence after
      Radical Prostatectomy.
AB  - AIM: To evaluate the efficacy of early duloxetine therapy in stress urinary
      incontinence occurring after radical prostatectomy (RP). MATERIAL AND METHOD:
      Patients that had RP were randomly divided into 2 groups following the removal of
      the urinary catheter. Group A patients (n = 28) had pelvic floor exercise and
      duloxetine therapy. Group B patients (n = 30) had only pelvic floor exercise. The
      incontinence status of the patients and number of pads were recorded and 1-hour
      pad test and Turkish validation of International Consultation on Incontinence
      Questionnaire-Short Form test were applied to the patients at the follow-up.
      RESULTS: When the dry state of the patients was evaluated, 5, 17, 3, and 2 of 28
      Group A patients stated that they were completely dry in the 3rd, 6th, 9th and
      12th month respectively and pad use was stopped. There was no continence in 30
      Group B in the first 3 months. Twelve, 6, and 8 patients stated that they were
      completely dry in the 6th, 9th and 12th month, respectively. But 3 of 4 patients
      in whom dryness could not be provided were using a mean of 7.6 pads in the first
      day and a mean of 1.3 pads after 1 year. When pad use of the patients was
      evaluated, the mean monthly number of pad use was determined to be 6.2 (4-8) in
      the initial evaluation, 2.7 (0-5) in the in 3rd month, 2 (0-3) in the 6th month
      and 1.6 (0-2) pad/d in the 9th month in the group taking medicine. The mean
      monthly number of pads used was determined to be 5.8 (4-8) in the initial
      evaluation, 4.3 (3-8) in the 3rd month, 3 (0-6) in the 6th month and 1.6 (0-6)
      pad/d in the 9th month in the group not taking medicine. CONCLUSION: According to
      the results, early duloxetine therapy in stress urinary incontinence that
      occurred after RP provided early continence.

PMID- 26195957
TI  - Research Findings on Overactive Bladder.
AB  - Several physiopathologic conditions lead to the manifestation of overactive
      bladder (OAB). These conditions include ageing, diabetes mellitus, bladder outlet
      obstruction, spinal cord injury, stroke and brain injury, Parkinson's disease,
      multiple sclerosis, interstitial cystitis, stress and depression. This review has
      discussed research findings in human and animal studies conducted on the above
      conditions. Several structural and functional changes under these conditions have
      not only been observed in the lower urinary tract, but also in the brain and
      spinal cord. Significant changes were observed in the following areas:
      neurotransmitters, prostaglandins, nerve growth factor, Rho-kinase, interstitial
      cells of Cajal, and ion and transient receptor potential channels. Interestingly,
      alterations in these areas showed great variation in each of the conditions of
      the OAB, suggesting that the pathophysiology of the OAB might be different in
      each condition of the disease. It is anticipated that this review will be helpful
      for further research on new and specific drug development against OAB. 

PMID- 26195964
TI  - Successful Surgical Management of Giant Condyloma Acuminatum (Buschke Lowenstein
      Tumor) in the Urethra of a Female Patient: A Case Report.
AB  - The Buschke-Lowenstein tumor (BLT) is a slow-growing, locally destructive
      verrucous plaque that typically appears on the penis but may occur elsewhere in
      the anogenital region. It most commonly is considered to be a regional variant of
      verrucous carcinoma. It is rare but accounts for 5-24% of all penile cancers. It
      can also affect the perineum and other portions of the genitalia. It was first
      described by Buschke and Lowenstein in 1925, and is also known as giant condyloma
      acuminatum (GCA). Regardless of the treatment modality, careful follow-up is
      recommended because of the high risk of recurrence and the possibility for
      malignant transformation in 30-56% of patients. We present a case of a 47-year
      old Hispanic female that presented to the urology clinic for dysuria and upon
      work-up was found to have a GCA. GCA typically affects the penis, although the
      perianal region, vulva, vagina, rectum, scrotum, perineum and bladder may be
      involved. To date, we believe this is the only reported case of GCA in the
      urethra of a female patient with sparing of the bladder. This lesion was
      successfully removed with wide local excision. We believe that further studies
      are needed to define this disease, identify its pathogenesis, and the most
      successful treatment protocol. 

PMID- 26195965
TI  - A Case Series of Spontaneous Rupture of the Urinary Bladder.
AB  - We report 2 cases of spontaneous bladder rupture related to chronic outlet
      obstruction and urinary retention. In both cases, focal perforation was
      identified within diverticula. Bladder rupture in the absence of trauma is a rare
      and serious event with a mortality rate approaching 50%. These injuries are often
      initially misdiagnosed and it is our goal to provide insight to the presentation,
      management and treatment of this rare event. 

PMID- 26195966
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000371653.]. 

PMID- 26195968
TI  - The Relationship between Serum Oxalic Acid, Central Hemodynamic Parameters and
      Colonization by Oxalobacter formigenes in Hemodialysis Patients.
AB  - BACKGROUND/OBJECTIVE: Elevated pulse wave velocity (PWV) and central aortic blood
      pressures are independent predictors of increased cardiovascular morbidity and
      mortality in hemodialysis (HD) patients. Oxalic acid is a uremic retention
      molecule that is extensively studied in the pathogenesis of calcium oxalate
      stones. Oxalobacter formigenes, a member of the colon microbiota, has important
      roles in oxalate homeostasis. Data regarding the colonization by and the exact
      role of O. formigenes in the pathogenesis of oxalic acid metabolism in HD
      patients are scant. Hence, we aimed to determine the relationship between fecal
      O. formigenes colonization, serum oxalic acid and hemodynamic parameters in HD
      patients with regard to the colo-reno-cardiac axis. METHODS: Fifty HD patients
      were enrolled in this study. PWV and central aortic systolic (cASBP) and
      diastolic blood pressures (cADBP) were measured with a Mobil-O-Graph (I.E.M.
      GmbH, Stolberg, Germany). Serum oxalic acid levels were assessed by ELISA, and
      fecal O. formigenes DNA levels were isolated and measured by real-time PCR.
      RESULTS: Isolation of fecal O. formigenes was found in only 2 HD patients. One of
      them had 113,609 copies/ml, the other one had 1,056 copies/ml. Serum oxalic acid
      levels were found to be positively correlated with PWV (r = 0.29, p = 0.03),
      cASBP (r = 0.33, p = 0.001) and cADBP (r = 0.42, p = 0.002) and negatively
      correlated with LDL (r = -0.30, p = 0.03). In multivariate linear regression
      analysis, PWV was independently predicted by oxalic acid, glucose and
      triglyceride. CONCLUSIONS: This is the first study that demonstrates the absence
      of O. formigenes as well as a relation between serum oxalic acid and cASBP, cADBP
      and PWV in HD patients. Replacement of O. formigenes with pre- and probiotics
      might decrease serum oxalic acid levels and improve cardiovascular outcomes in HD
      patients.

PMID- 26195967
TI  - Long-Term Risk of Progressive Chronic Kidney Disease in Patients with Severe
      Acute Kidney Injury Requiring Dialysis after Coronary Artery Bypass Surgery.
AB  - AIM: Few studies have evaluated patients after cardiac surgery for subsequent
      chronic kidney disease (CKD) which increases cardiovascular morbidity and
      mortality. This study aimed to ascertain the long-term renal outcome in adult
      patients with severe acute kidney injury (AKI) after coronary artery bypass graft
      (CABG) surgery. METHODS: This is a single-center retrospective cohort study of
      consecutive adult patients who received acute dialysis for AKI after CABG between
      February 8, 2009 and January 30, 2011. Data on pre- and intra-operative factors
      were retrieved from electronic medical records. The primary endpoint was CKD
      progression as defined by dialysis dependence or doubling of serum creatinine
      from the pre-operative level. Secondary endpoints included in-hospital mortality
      and renal function at 3 months and 1 year. RESULTS: Fifty-five patients required
      acute dialysis after CABG. The median age was 67 years (IQR: 61, 75), and 70.9%
      were male. Median pre-operative serum creatinine was 157 umol/l (IQR: 122, 203).
      A total of 19 patients (34.5%) died. The median follow-up time for hospital
      survivors was 44.2 months (IQR: 25.0, 49.4) after surgery. Among the 36
      survivors, 14 patients (38.9%) reached the primary endpoint. Patients with CKD
      progression had higher pre-operative serum creatinine [median 214 umol/l (IQR:
      159, 399) vs. 155 umol/l (112, 187), p = 0.015] and lower eGFR [median 20.4
      ml/min/1.73 m(2) (IQR: 11.9, 38.2) vs. 39.9 ml/min/1.73 m(2) (25.9, 55.5), p =
      0.027] compared to those who did not have CKD progression. CONCLUSION: Patients
      with severe AKI after CABG are at high risk of long-term renal dysfunction and
      should be monitored regularly for deterioration.

PMID- 26195969
TI  - Hyperuricemia: A Biomarker of Renal Hemodynamic Impairment.
AB  - BACKGROUND: Many epidemiological, clinical, and experimental reports have
      demonstrated an association between serum uric acid concentration and a variety
      of cardiovascular and renal diseases, particularly in hypertension. At present,
      there seems to be no resolution to the question whether this relationship is
      causal or coincidental. SUMMARY: This discussion examines a number of biological,
      pathophysiological, fundamental, and clinical relationships between serum uric
      acid concentration and several of these disorders. To this end, discussion and
      review provide some specific insight conclusions and recommendations related to
      their clinical relevance. KEY MESSAGES: We suggest that, in most instances
      (especially in patients with essential hypertension), the increase in serum uric
      acid concentration is coincidental, serving as a useful biomarker that relates
      the magnitude of circulating plasma uric acid concentration with the extent of
      impaired cardiovascular and renal function. Moreover, the value of certain
      pharmaceutical agents affecting the serum uric acid level should be considered
      carefully by taking into consideration the associated pathophysiological
      derangements.

PMID- 26195970
TI  - Ambulatory Blood Pressure Monitoring in Lean, Obese and Diabetic Children and
      Adolescents.
AB  - AIM: To determine if children and adolescents who have obesity (Ob) or type 2
      diabetes (T2DM) of relatively short duration have impaired cardiovascular
      function compared with lean subjects using 24-hour ambulatory blood pressure as a
      surrogate measure of evaluation. METHODS: We enrolled 100 African-Caribbean
      subjects (45 males/55 females), mean ages 14.4-15.2 years (range 11.8-18.5 years)
      and Tanner stage 4.2-4.8. Mean BMI for the Ob (n = 40), T2DM (n = 39) and lean (n
      = 21) groups were 40.3, 34.2 and 20.8, respectively (p < 0.01, Ob and T2DM vs.
      lean). Mean hemoglobin A1c in lean and Ob was 5.4 and 5.5% compared to 8.8% in
      T2DM (p < 0.001, T2DM vs. lean and Ob). Ambulatory blood pressure was recorded
      every 20 min over 24 h using Spacelabs 70207. RESULTS: Mean 24-hour, daytime and
      nighttime systolic blood pressure was significantly higher in Ob and T2DM
      compared with lean subjects (mean 24-hour 117 and 120 vs. 109 mm Hg; daytime 121
      and 123 vs. 113 mm Hg; and nighttime 109 and 115 vs. 101 mm Hg; p < 0.01 for all
      time periods). The nocturnal systolic dip in Ob and T2DM did not differ from that
      of lean, whereas nocturnal diastolic dip decreased significantly in Ob and T2DM
      compared to lean (11.5 and 10.4 vs. 20.6 mm Hg; p < 0.01). Mean pulse pressure
      was significantly increased in the Ob and T2DM groups compared to lean subjects
      (51 and 54 vs. 45 mm Hg; p < 0.01). CONCLUSION: Adolescent Ob and T2DM groups
      share adverse risk factors, which may be harbingers of adult cardiovascular
      events.

PMID- 26195971
TI  - Admission Glucose Levels and the Risk of Acute Kidney Injury in Nondiabetic ST
      Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous
      Coronary Intervention.
AB  - BACKGROUND: Hyperglycemia upon admission is associated with an increased risk for
      acute kidney injury (AKI) in ST segment elevation myocardial infarction (STEMI)
      patients undergoing primary percutaneous coronary intervention (PCI). However,
      the relation of this association to the absence of diabetes mellitus (DM) is less
      studied. We evaluated the effect of acute hyperglycemia levels on the risk of AKI
      among STEMI patients without DM who were all treated with primary PCI. METHODS:
      We retrospectively studied 1,065 nondiabetic STEMI patients undergoing primary
      PCI. Patients were stratified according to admission glucose levels into normal
      (<140 mg/dl), mild (140-200 mg/dl), and severe (>200 mg/dl) hyperglycemia groups.
      Medical records were reviewed for the occurrence of AKI. RESULTS: The mean age
      was 61 +/- 13 years and 81% were males. Hyperglycemia upon hospital admission was
      present in 402 of 1,065 patients (38%). Patients with severe admission
      hyperglycemia had a significantly higher rate of AKI compared to patients with no
      or mild hyperglycemia (20 vs. 7 and 8%, respectively; p = 0.001) and had a
      significantly greater serum creatinine change throughout hospitalization (0.17
      vs. 0.09 and 0.07 mg/dl, respectively; p = 0.04). In multivariate logistic
      regression, severe hyperglycemia emerged as an independent predictor of AKI (OR =
      2.46, 95% CI 1.16-5.28; p = 0.018). CONCLUSION: Severe admission hyperglycemia is
      an independent risk factor for the development of AKI among nondiabetic STEMI
      patients undergoing primary PCI.

PMID- 26195972
TI  - Comparison of Carvedilol and Metoprolol for Preventing Contrast-Induced
      Nephropathy after Coronary Angiography.
AB  - AIMS: Contrast-induced nephropathy (CIN) is one of the most common causes of
      hospital-acquired acute renal failure. Oxidative stress and vasoconstriction
      might play key roles in its pathogenesis. In a few experimental models,
      antioxidant properties of carvedilol have been documented. The aim of this study
      was to analyze and compare the effects of carvedilol and metoprolol on the
      development of CIN in patients undergoing coronary angiography. METHODS: One
      hundred patients currently taking metoprolol and 100 patients currently taking
      carvedilol were enrolled into the study. Venous blood samples were obtained
      before and 48 h after contrast administration. Cystatin C and malondialdehyde
      values were examined and compared. CIN was defined as a creatinine increase of at
      least 25% or 0.5 mg/dl from the baseline value. RESULTS: Seven patients in the
      carvedilol group (7%) and 22 patients in the metoprolol group (22%) developed CIN
      (p = 0.003). In the metoprolol group, the median cystatin C concentration
      increased significantly from 978 to 1,086 ng/ml (p = 0.001) 48 h after
      radiocontrast administration. In the carvedilol group, the median cystatin C
      concentration did not change significantly (1,143 vs. 1,068 ng/ml; p = 0.94). In
      the metoprolol group, the mean malondialdehyde concentration increased
      significantly from 7.09 +/- 1.48 to 8.38 +/- 2.6 nmol/l (p < 0.001). In the
      carvedilol group, the mean serum malondialdehyde concentration did not change
      significantly (7.44 +/- 1.21 vs. 7.56 +/- 1.11 nmol/l; p = 0.59). CONCLUSION:
      When compared to metoprolol, carvedilol might decrease oxidative stress and
      subsequent development of CIN.

PMID- 26195973
TI  - Arrhythmogenic Remodeling in Murine Models of Deoxycorticosterone Acetate-Salt
      Induced and 5/6-Subtotal Nephrectomy-Salt-Induced Cardiorenal Disease.
AB  - BACKGROUND: Renal failure is associated with adverse cardiac remodeling and
      sudden cardiac death. The mechanism leading to enhanced arrhythmogenicity in the
      cardiorenal syndrome is unclear. The aim of this study was to characterize
      electrophysiological and tissue alterations correlated with enhanced
      arrhythmogenicity in two distinct mouse models of renal failure. METHODS: Thirty
      week-old 129Sv mice received a high-salt diet and deoxycorticosterone acetate
      (DOCA) for 8 weeks, followed by an additional period of high-salt diet for 27
      weeks (DOCA-salt aged model). Adult CD-1 mice were submitted to 5/6-subtotal
      nephrectomy (SNx) and treated for 11 weeks with a high-salt diet (SNx-salt adult
      model). Vulnerability to arrhythmia as well as conduction velocities (CVs) of the
      hearts were determined ex vivo with epicardial mapping. Subsequently, the hearts
      were characterized for connexin 43 (Cx43) and fibrosis. RESULTS: DOCA-salt and
      SNx-salt mice developed renal dysfunction characterized by albuminuria. Heart,
      lung and kidney weights were increased in DOCA-salt mice. Both DOCA-salt and SNx
      salt mice were highly susceptible to ventricular arrhythmias. DOCA-salt mice had
      a significant decrease in both longitudinal and transversal CV in the left
      ventricle. Histological analysis revealed a significant reduction in Cx43
      expression as well as an increase in interstitial fibrosis in both DOCA-salt and
      SNx-salt mice. CONCLUSION: DOCA-salt and SNx-salt treatment induced renal
      dysfunction, which resulted in structural and electrical cardiac remodeling and
      enhanced arrhythmogenicity. The reduced Cx43 expression and increased fibrosis
      levels in these hearts are likely candidates for the formation of the
      arrhythmogenic substrate.

PMID- 26195974
TI  - Contrast Medium-Induced Acute Kidney Injury.
AB  - Contrast medium-induced acute kidney injury (CI-AKI) is a predominant cause of
      hospital-acquired renal insufficiency. With an increasing number of contrast
      medium-enhanced radiological procedures being performed in a rapidly increasing
      ageing population in the Western world, it is imperative that more attention is
      given to understand the aetiology of CI-AKI to devise novel diagnostic methods
      and to formulate effective prophylactic and therapeutic regimens to reduce its
      incidence and its associated morbidity and mortality. This article presents high
      yield information on the above-mentioned aspects of CI-AKI, primarily based on
      results of randomised controlled trials, meta-analyses, systematic reviews and
      international consensus guidelines. 

PMID- 26195975
TI  - Evidence of Mild Liver Dysfunction Identifies Stable Heart Failure Outpatients
      with Reversible Renal Dysfunction.
AB  - BACKGROUND: In decompensated heart failure (HF), reversible renal dysfunction
      (RD) is more frequently observed in patients with mild liver dysfunction likely
      due to the shared pathophysiologic factors involved. The objective of this study
      was to determine if these findings also apply to stable HF outpatients. METHODS:
      Patients in the Beta-Blocker Evaluation of Survival Trial (BEST) were studied.
      Improvement in renal function (IRF) was defined as a 20% improvement in the
      estimated glomerular filtration rate from baseline to 3 months. RESULTS: Elevated
      bilirubin (BIL), aspartate aminotransferase (AST), and alanine aminotransferase
      (ALT) were significantly associated with signs of congestion or poor perfusion.
      IRF occurred in 12.0% of all patients and was more common in those with elevated
      BIL (OR = 1.5, p = 0.003), ALT (OR = 1.4, p = 0.01), and AST (OR = 1.4, p =
      0.01). In a model containing all 3 liver parameters and baseline characteristics,
      including markers of congestion/poor perfusion, BIL (OR = 1.6, p = 0.001) and ALT
      (OR = 1.7, p < 0.001) were independently associated with IRF. CONCLUSIONS:
      Biochemical evidence of mild liver dysfunction is significantly associated with
      IRF in stable HF outpatients. Given the widespread availability and low cost of
      these markers, additional research is necessary to determine the utility of these
      parameters in identifying patients with reversible RD who may benefit from
      cardiorenal interventions.

PMID- 26195976
TI  - Balance and Mobility as Predictors of Post-Stroke Cognitive Impairment.
AB  - BACKGROUND: The number of patients with cognitive impairment following stroke is
      increasing due to the rise in the number of stroke survivors. Health authorities
      highlight the need for prediction and early diagnostics. The aims of this study
      were to investigate if balance and mobility may predict cognitive impairment 1
      year after stroke. METHODS: The participants were patients with first-ever stroke
      or transient ischaemic attack (TIA). The exclusion criteria were pre-stroke
      cognitive impairment and dementia. Measurements of balance comprised the Berg
      Balance Scale (BBS) and the Figure of Eight test (Fig8). Mobility was measured by
      maximum walking speed and the Timed Up and Go test. Dementia and mild cognitive
      impairment were merged into a main outcome: cognitive impairment. Unadjusted and
      adjusted multivariate logistic regression models were performed. RESULTS: One
      hundred and eighty subjects performed balance and mobility measures at baseline,
      and 158 participated in the follow-up; 13 died and 9 did not complete the follow
      up. Two variables made a significant contribution in the adjusted analyses (Fig8,
      BBS). The strongest predictor of cognitive impairment was Fig8 with an odds ratio
      of 1.06. CONCLUSION: The results of Fig8 and BBS measured in the acute phase of
      stroke were predictors of cognitive impairment 1 year later in this cohort of
      first-ever stroke or TIA.

PMID- 26195977
TI  - Clinical and Neuropsychological Differences between Mild Parkinson's Disease
      Dementia and Dementia with Lewy Bodies.
AB  - BACKGROUND: The specific profile of dementia in Parkinson's disease (PDD) and
      dementia with Lewy bodies (DLB) in the earliest stages of dementia is still
      unclear and subject of considerable controversy. METHODS: We investigated 27 PDD
      patients and 24 DLB patients with parkinsonism in the early stage of dementia,
      i.e. with a Mini-Mental State Examination score of >=24. RESULTS: Compared to
      PDD, patients with DLB demonstrated significantly lower scores when testing
      attention and executive functions [modified card sorting test (p < 0.001) and
      digit span backward (p < 0.02)], as well as when testing constructive abilities
      [copy of complex designs (p = 0.001) and pentagon (p < 0.001)]. Using logistic
      regression analysis, diagnosis was predicted from the cognitive profile, with an
      overall accuracy of 88.2%. In addition, PDD patients showed a significantly
      higher Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore (p <
      0.001) as well as higher UPDRS motor item scores [tremor at rest (p = 0.01) and
      bradykinesia (p = 0.001)]. CONCLUSIONS: The cognitive profile in PDD differs from
      that in DLB in the early stage of dementia, with worse performance on tests of
      attention and executive functions and constructive abilities in DLB compared to
      PDD patients. In contrast, motor symptoms are more severe in PDD than in DLB.

PMID- 26195978
TI  - A Cluster Randomized Controlled Trial of Nonpharmacological Interventions for Old
      Old Subjects with a Clinical Dementia Rating of 0.5: The Kurihara Project.
AB  - BACKGROUND: Evidence as to the benefits of nonpharmacological interventions for
      the boundary state between normal aging and dementia [mild cognitive impairment
      or a Clinical Dementia Rating (CDR) of 0.5] remains weak due to a lack of
      positive controls. AIMS: To directly compare the effects of cognitive
      interventions (CI), physical activities (PA) and a group reminiscence approach
      (GRA), we conducted a pilot study on the basis of a cluster randomized controlled
      trial design. METHOD: A total of 127 participants aged >74 years with a CDR of
      0.5 were cluster randomized into three groups for CI, PA and GRA. The
      intervention lasted 12 weeks and consisted of weekly group sessions and home
      assignments. Mini-Mental State Examination (MMSE), Trail Making Test part A (TMT
      A), word fluency (WF), 6-meter walk time and Quality of Life (QOL) Face Scale
      scores were evaluated as primary outcomes. RESULTS: Methodology-related benefits
      of CI and PA were found for MMSE scores and walk time, respectively. TMT-A, WF
      and QOL Face Scale scores improved irrespective of the methodologies used.
      CONCLUSIONS: Our findings suggest that CI and PA may be beneficial to cognitive
      and physical abilities, respectively. Executive functions and QOL may improve
      irrespective of the intervention methodologies used.

PMID- 26195979
TI  - The Positivity Effect on the Intensity of Experienced Emotion and Memory
      Performance in Mild Cognitive Impairment and Dementia.
AB  - AIMS: We examined the 'positivity effect' on memory performance in mild cognitive
      impairment (MCI) and dementia patients. METHODS: In 109 subjects (28 controls, 32
      with MCI, 27 with mild and 32 with moderate dementia), we investigated free
      recalls (immediate and delayed) and recognition of 12 pictures. Moreover, the
      emotional valence of the pictures perceived and the emotions evoked in the
      subjects were evaluated. RESULTS: Patients with mild and moderate dementia
      recalled fewer pictures than those with MCI or the healthy controls. Across the
      groups, the positive pictures were better memorized and induced a higher arousal
      than the negative or neutral ones. CONCLUSIONS: Our findings indicate a
      positivity effect on memory performance and intensity of experience not only in
      healthy elderly patients but also in those with MCI or mild and moderate
      dementia. This effect does not refer to the compliance of the patients
      investigated since they perceived and experienced the pictures in the expected
      way.

PMID- 26195980
TI  - Relationship between Dementia Severity and Behavioral and Psychological Symptoms
      of Dementia in Dementia with Lewy Bodies and Alzheimer's Disease Patients.
AB  - BACKGROUND/AIMS: Behavioral and psychological symptoms of dementia (BPSD) are
      common in the clinical manifestation of dementia. Although most patients with
      dementia exhibit some BPSD during the course of the illness, the association of
      BPSD with the stage of dementia remains unclear. It was the aim of this study to
      evaluate the impact of severity of dementia on the expression of BPSD in patients
      with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). METHODS:
      Ninety-seven patients with DLB and 393 patients with AD were recruited from 8
      dementia clinics across Japan. BPSD were assessed by the Neuropsychiatric
      Inventory (NPI). A relationship between BPSD and dementia stage classified by the
      Clinical Dementia Rating (CDR) in each type of dementia was assessed. RESULTS: No
      significant difference was seen in NPI total score across CDR staging in the DLB
      group. On the other hand, the NPI total score significantly increased with
      dementia stage in the AD group. CONCLUSION: The relationship of dementia stage
      with the expression of BPSD was different according to the type of dementia. BPSD
      and dementia stage were correlated in AD subjects, in whom psychiatric symptoms
      increase as the disease progresses, but not in DLB subjects.

PMID- 26195981
TI  - Severe, Persistent and Fatal Delirium in Psychogeriatric Patients Admitted to a
      Psychiatric Hospital.
AB  - BACKGROUND/AIMS: Although delirium is generally regarded as a transient syndrome,
      persistence of delirium in patients with cognitive impairment - even with fatal
      outcome - has been reported as well. This study aims to describe the clinical
      features and neuropathological correlates of this type of delirium. METHODS:
      Inclusion criteria for this case series were: (1) severe persistent delirium
      until death, (2) history of cognitive decline and (3) consent for brain autopsy.
      Medical records were examined in combination with collected clinical data and
      neuropathological findings. RESULT: In 15 patients, all living at home before
      admission, episodes with delirium lasted for 4.2 months on average. No distinct
      medical causes of persistent delirium could be identified. Pathological diagnoses
      included Alzheimer's disease and dementia with Lewy bodies as well as single
      cases of Creutzfeldt-Jakob disease and progressive supranuclear palsy.
      CONCLUSION: Severe, persistent and fatal delirium in patients with cognitive
      impairment can occur relatively early in the disease trajectory and is associated
      with diverse neuropathologies.

PMID- 26195983
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000363621.]. 

PMID- 26195982
TI  - The Q* Index: A Useful Global Measure of Dementia Screening Test Accuracy?
AB  - BACKGROUND/AIMS: Single, global or unitary, indicators of test diagnostic
      performance have intuitive appeal for clinicians. The Q* index, the point in
      receiver operating characteristic (ROC) curve space closest to the ideal top left
      hand corner and where test sensitivity and specificity are equal, is one such
      measure. METHODS: Datasets from four pragmatic accuracy studies which examined
      the Mini-Mental State Examination, Addenbrooke's Cognitive Examination-Revised,
      Montreal Cognitive Assessment, Test Your Memory test, and Mini-Addenbrooke's
      Cognitive Examination were examined to calculate and compare the Q* index, the
      maximal correct classification accuracy, and the maximal Youden index, as well as
      the sensitivity and specificity at these cutoffs. RESULTS: Tests ranked similarly
      for the Q* index and the area under the ROC curve (AUC ROC). The Q* index cutoff
      was more sensitive (and less specific) than the maximal correct classification
      accuracy cutoff, and less sensitive (and more specific) than the maximal Youden
      index cutoff. CONCLUSION: The Q* index may be a useful global parameter
      summarising the test accuracy of cognitive screening instruments, facilitating
      comparison between tests, and defining a possible test cutoff value. As the point
      of equal sensitivity and specificity, its use may be more intuitive and appealing
      for clinicians than AUC ROC.

PMID- 26195984
TI  - Retrospective case note review of chronic spontaneous urticaria outcomes and
      adverse effects in patients treated with omalizumab or ciclosporin in UK
      secondary care.
AB  - BACKGROUND: Omalizumab is approved in the UK as add-on treatment for chronic
      spontaneous urticaria (CSU) in patients with inadequate response to H1
      antihistamines. Ciclosporin is an established but unlicensed 3rd line option for
      CSU. Two parallel retrospective observational studies were conducted to describe
      outcomes of treatment and adverse events with omalizumab or ciclosporin for CSU
      treatment. METHODS: Data from UK specialist centres prescribing omalizumab (five
      centres) or ciclosporin (three centres) in CSU patients were collected from
      hospital records by clinical staff and pooled for analysis. RESULTS: Forty-six
      patients prescribed omalizumab and 72 patients prescribed ciclosporin were
      included. Twenty-two (48%) omalizumab-treated patients had paired Urticaria
      Activity Scores (UAS7), showing a 25.4 point improvement during treatment (P <
      0.0001). Paired Dermatology Life Quality Index (DLQI) was available in 28 (61%)
      omalizumab-treated and 17 (24%) ciclosporin-treated patients. At least a 75%
      improvement in DLQI score was observed in 79% of omalizumab-treated and 41% of
      ciclosporin-treated patients, and 65% of omalizumab-treated patients had complete
      resolution of their quality-of-life impairment (DLQI 0-1) versus 21% of
      ciclosporin-treated patients. Clinician comments reported symptom clearance in
      15/36 (42%) omalizumab-treated and 10/60 (17%) ciclosporin-treated patients.
      Proportions of patients with adverse events were similar but those for omalizumab
      resembled CSU symptoms, making causality assignment difficult, whereas those for
      ciclosporin were consistent with its known adverse effect profile. CONCLUSIONS:
      Validated patient-reported measures of disease severity and quality of life
      should be used routinely in CSU management. Based on clinician comments and DLQI
      scores, symptoms and quality of life showed a greater improvement in the
      omalizumab-treated cohort than in the ciclosporin-treated cohort.

PMID- 26195985
TI  - Cervical intraepithelial lesions in females attending Women's Health Clinics in
      Alexandria, Egypt.
AB  - BACKGROUND: Data from Egyptian studies provide widely varying estimates on the
      prevalence of preinvasive cervical lesions. The aim of this study was to estimate
      the rate of cervical intraepithelial neoplasia (CIN) in Egyptian women living in
      Alexandria to clarify the need for implementing a national organized screening
      program and a vaccination program in our community. MATERIALS AND METHODS: The
      study was conducted over a 6 years period and covered the different socioeconomic
      levels to have a representative sample for women living in Alexandria. All women
      included did not have any cervical disorder related complaints. Conventional Pap
      smears were obtained and diagnosed using the Bethesda system. Women with abnormal
      Pap smears were managed according to the 2006 consensus guidelines within the
      available facilities. Persistent abnormal cytological results were referred for
      colposcopic biopsy. Histological results were grouped into: Reactive changes, CIN
      1, CIN 2/CIN 3 and adenocarcinoma in-situ (AIS). RESULTS: Out of the 6173 smears
      included in the study 6072 (98.36%) were normal and only 101 (1.63%) were
      abnormal. After colposcopic biopsies, 0.08% had CIN 1, 0.03% had CIN 2, 3 and
      0.01% had AIS. CONCLUSION: We concluded that cervical cancer screening programs,
      although life-saving for a number of women, are not a sufficiently high priority
      in our community. Money for national health screening programs should preferably
      be directed more towards recruiting women for breast cancer screening, since
      breast cancer accounts for about 33% of all female cancers in Egypt ranking
      number one, while cervical cancer ranks number 13.

PMID- 26195986
TI  - Survey of cytopathologists and cytotechnologists for the clinical impact of the
      use of atypia or follicular lesion of undetermined significance.
AB  - BACKGROUND: The cytologic diagnosis of atypia of undetermined significance or
      follicular lesion of undetermined significance (AUS/FLUS) is controversial
      because of variation in how it is applied in practice, as well as uncertainty
      about patient management. We aimed to assess the percentage of thyroid fine
      needle aspiration biopsies (FNABs) with AUS/FLUS diagnoses in different North
      American and European practice settings (e.g. community, academic, etc.), assess
      whether patients were managed according to current guidelines, and determine
      patient outcomes. MATERIALS AND METHODS: A detailed questionnaire survey was
      posted in secure websites used separately by cytopathologists and
      cytotechnologists. The questionnaire was posted from August 1 through December
      31, 2013. RESULTS: Endocrinologists and cytopathologists performed 51.7% and
      37.1% of thyroid FNABs, respectively. The Bethesda reporting system for thyroid
      FNAB was used in 90% of practices. The rate of AUS/FLUS varied widely among
      institutions, with 46.1% of represented institutions reporting AUS/FLUS rates of
      3-10%. The median follow-up rate of patients with an initial AUS/FLUS diagnosis
      was 70% (range, 10-100%). For the majority of represented institutions (86.4%),
      patients with initial AUS/FLUS diagnosis had follow-up with endocrinologists. Of
      repeat AUS/FLUS thyroid FNABs, a median of 52% was considered benign, and 18%
      were suspicious of or positive for malignancy (median, 10% and 7.5%,
      respectively). CONCLUSIONS: Reporting of the AUS/FLUS category varied widely
      among different institutions. The median follow-up rate was lower than published
      guidelines. The most common follow-up diagnosis was benign thyroid nodule.
      Improved standardization of cytologic criteria should be adopted to reduce such
      variation.

PMID- 26195988
TI  - lobChIP: from cells to sequencing ready ChIP libraries in a single day.
AB  - BACKGROUND: ChIP-seq is the method of choice for genome-wide studies of protein
      DNA interactions. We describe a new method for ChIP-seq sample preparation,
      termed lobChIP, where the library reactions are performed on cross-linked ChIP
      fragments captured on beads. RESULTS: The lobChIP method was found both to reduce
      time and cost and to simplify the processing of many samples in parallel. lobChIP
      has an early incorporation of barcoded sequencing adaptors that minimizes the
      risk of sample cross-contamination and can lead to reduced amount of adaptor
      dimers in the sequencing libraries, while allowing for direct decross-linking and
      amplification of the sample. CONCLUSIONS: With results for histone modifications
      and transcription factors, we show that lobChIP performs equal to or better than
      standard protocols and that it makes it possible to go from cells to sequencing
      ready libraries within a single day.

PMID- 26195987
TI  - Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and
      beyond.
AB  - The chemical modification of DNA bases plays a key role in epigenetic gene
      regulation. While much attention has been focused on the classical epigenetic
      mark, 5-methylcytosine, the field garnered increased interest through the recent
      discovery of additional modifications. In this review, we focus on the epigenetic
      regulatory roles of DNA modifications in animals. We present the symmetric
      modification of 5-methylcytosine on CpG dinucleotide as a key feature, because it
      permits the inheritance of methylation patterns through DNA replication. However,
      the distribution patterns of cytosine methylation are not conserved in animals
      and independent molecular functions will likely be identified. Furthermore, the
      discovery of enzymes that catalyse the hydroxylation of 5-methylcytosine to 5
      hydroxymethylcytosine not only identified an active demethylation pathway, but
      also a candidate for a new epigenetic mark associated with activated
      transcription. Most recently, N6-methyladenine was described as an additional
      eukaryotic DNA modification with epigenetic regulatory potential. Interestingly,
      this modification is also present in genomes that lack canonical cytosine
      methylation patterns, suggesting independent functions. This newfound diversity
      of DNA modifications and their potential for combinatorial interactions indicates
      that the epigenetic DNA code is substantially more complex than previously
      thought. 

PMID- 26195990
TI  - Unpacking the "Black Box" of Race-Ethnic Variation in Fertility.
AB  - Race-ethnic differences in a range of childbearing behaviors are long-standing
      and well-documented, and these differences are attenuated, but not eliminated,
      when accounting for socioeconomic disparities. The residual differences are often
      attributed to vague and untested variation across race-ethnic groups in
      knowledge, attitudes, psychological attributes, normative beliefs, and social
      context. We use the longitudinal Toledo Adolescent Relationship Study (TARS),
      which contains a rich set of such factors measured in early adolescence, to
      assess whether they contribute to race-ethnic differences in having a birth among
      men and women ages 17-24 (n=1,042). Specifically, we test whether individual
      attitudes, religiosity, and academic behaviors; knowledge and behaviors regarding
      sex and dating; peer normative context; and parental communication about sex
      account for variation in the risk of an early birth. We find that socioeconomic
      factors attenuate but do not reduce differences between Black, Hispanic, and
      White respondents. Including adolescent academic performance and early entry into
      sex reduces the Black-White difference in the odds of early fertility to
      nonsignificance; however, beyond socioeconomic status, none of the broad range of
      factors further attenuate Hispanic-White differences, which remain large and
      statistically significant.

PMID- 26195989
TI  - Secondary findings and carrier test frequencies in a large multiethnic sample.
AB  - BACKGROUND: Besides its growing importance in clinical diagnostics and
      understanding the genetic basis of Mendelian and complex diseases, whole exome
      sequencing (WES) is a rich source of additional information of potential clinical
      utility for physicians, patients and their families. We analyzed the frequency
      and nature of single nucleotide variants (SNVs) considered secondary findings and
      recessive disease allele carrier status in the exomes of 8554 individuals from a
      large, randomly sampled cohort study and 2514 patients from a study of presumed
      Mendelian disease having undergone WES. METHODS: We used the same sequencing
      platform and data processing pipeline to analyze all samples and characterized
      the distributions of reported pathogenic (ClinVar, Human Gene Mutation Database
      (HGMD)) and predicted deleterious variants in the pre-specified American College
      of Medical Genetics and Genomics (ACMG) secondary findings and recessive disease
      genes in different ethnic groups. RESULTS: In the 56 ACMG secondary findings
      genes, the average number of predicted deleterious variants per individual was
      0.74, and the mean number of ClinVar reported pathogenic variants was 0.06. We
      observed an average of 10 deleterious and 0.78 ClinVar reported pathogenic
      variants per individual in 1423 autosomal recessive disease genes. By repeatedly
      sampling pairs of exomes, 0.5 % of the randomly generated couples were at 25 %
      risk of having an affected offspring for an autosomal recessive disorder based on
      the ClinVar variants. CONCLUSIONS: By investigating reported pathogenic and
      novel, predicted deleterious variants we estimated the lower and upper limits of
      the population fraction for which exome sequencing may reveal additional
      medically relevant information. We suggest that the observed wide range for the
      lower and upper limits of these frequency numbers will be gradually reduced due
      to improvement in classification databases and prediction algorithms.

PMID- 26195992
TI  - Prevalence of Mental Health Problems in Children and Its Associated Socio
      Familial Factors in Urban Population of Semnan, Iran (2012).
AB  - BACKGROUND: The World Health Organization (WHO) defines mental health as "a state
      of well-being in which every individual realizes own potential, can cope with the
      normal pressures of life, is able to work effectively, and can make a
      contribution to community". OBJECTIVES: Mental Health Problems (MHP) is a great
      concern for all societies in terms of its burden and impact. This survey screened
      MHP and its impact in an Iranian urban population aged 6 - 12 years old, and
      explored its associated socio-familial factors. PATIENTS AND METHODS: The survey
      was conducted in the elementary schools of Semnan, using random cluster sampling.
      Collection and analysis of data was performed using the parent version of the
      "Strengths and Difficulties Questionnaire (SDQ)" and survey commands of Stata
      nine, taking into account cluster effect and population weights. Associations
      were assessed by fitting simple and multiple logistic regression models. P < 0.05
      was considered significant. RESULTS: With regard to the SDQ total score, 19.3%
      (95% CI: 8.6, 30.1) scored above the normal threshold (9.6% abnormal, 9.7%
      borderline). The frequency of problems ranged between 16.1% (peer problems) and
      8.4% (emotional symptoms), and in all subscales boys were affected more than
      girls. The impact score was abnormal in 68.4% of all children, and was greater in
      girls than in boys. "A previously diagnosed mental health disorder" (OR = 11.11,
      95% CI: 5.55, 25.00), "male gender" (OR = 1.43, 95% CI: 1.10, 1.87 and "less time
      spent with the child by father" (OR = 1.61, 95% CI: 1.20, 2.17) were
      significantly associated with an abnormal SDQ. CONCLUSIONS: The high rate of MHP
      in 6 - 12 year-old children and the lack of any significant correlation with
      their age, underpins the importance of early screening for MHP in schools, with
      particular focus on high risk groups.

PMID- 26195991
TI  - Cellular and Extracellular Matrix Basis for Heterogeneity in Mitral Annular
      Contraction.
AB  - PURPOSE: Regional heterogeneity in mitral annular contraction, which is generally
      ascribed to the fibrous vs. muscular annular composition, ensures proper leaflet
      motion and timing of coaptation. It is unknown whether the fibroblast-like cells
      in the annulus modulate this heterogeneity, even though valvular interstitial
      cells (VICs) can be mechanically "activated." METHODS: Fourteen sheep underwent
      implantation of radiopaque markers around the mitral annulus defining four
      segments: septal (SEPT), lateral (LAT), and anterior (ANT-C) and posterior (POST
      C) commissures. Segmental annular contraction was calculated using biplane
      videofluoroscopy. Immunohistochemistry of annular cross sections assessed
      regional matrix content, matrix turnover, and cell phenotype. Micropipette
      aspiration measured the Young's modulus of the leaflets adjacent to the
      myocardial border. RESULTS: Whereas SEPT contained more collagen I and III, LAT
      demonstrated more collagen and elastin turnover as shown by greater decorin,
      lysyl oxidase, and matrix metalloprotease (MMP)-13 and smooth muscle alpha-actin
      (SMaA). This greater matrix turnover paralleled greater annular contraction in
      LAT vs. SEPT (22.5% vs. 4.1%). Similarly, POST-C had more SMaA and MMP13 than ANT
      C, consistent with greater annular contraction in POST-C (18.8% vs. 11.1%).
      Interestingly, POST-C had the greatest effective modulus, significantly higher
      than LAT. CONCLUSIONS: These data suggest that matrix turnover by activated VICs
      relates to annular motion heterogeneity, maintains steady-state mechanical
      properties in the annulus, and could be a therapeutic target when annular motion
      is impaired. Conversely, alterations in this heterogeneous annular contraction,
      whether through disease or secondary to ring annuloplasty, could disrupt this
      normal pattern of cell-mediated matrix remodeling and further adversely impact
      mitral valve function.

PMID- 26195993
TI  - Regional Disparities in Sedentary Behaviors and Meal Frequency in Iranian
      Adolescents: The CASPIAN-III Study.
AB  - BACKGROUND: The prevalence of obesity is increasing among Iranian youngsters like
      other developing countries. OBJECTIVES: This study was conducted to assess
      regional disparities in sedentary behaviors and meal frequency in Iranian
      adolescents. PATIENTS AND METHODS: In this national survey, 5682 students aged 10
      - 18 years from urban and rural districts of 27 provinces of Iran were selected
      via stratified multi-stage sampling method. The country was classified into four
      sub-national regions, based on criteria of the combination of geography and
      socioeconomic status (SES). Mean of meal frequency and physical activity levels
      as well as prevalence of omitting meals and sedentary behavior were compared
      across regions with different SES after stratifying with sex and age group.
      RESULTS: Meal frequency in lower socio-economic regions was significantly higher
      than two other regions in 10 - 13 and 10 - 18 years old groups (P trend < 0.001).
      However, the mean of working hours with computer was linearly increased with
      increasing the SES in studied regions (P trend < 0.001), whereas the
      corresponding figure was not significant for the mean of watching TV (P trend >
      0.05). Frequency of adolescents omitting their meals was higher in higher SES
      regions especially in West Iran (P < 0.001) in 10 - 13 years old age group.
      Having personal computer and working with it more than two hours per day mainly
      was observed in central Iran which ranked as the highest SES group. CONCLUSIONS:
      Efforts to ensure Iranian youth meet healthy food habits and screen time
      guidelines include limiting access to screen technologies and encouraging parents
      to monitor their own screen time is required.

PMID- 26195994
TI  - Cardiac Tamponade: A Rare Presentation of Childhood Hypothyroidism.

PMID- 26195995
TI  - Horseshoe Lung Associated With Holt-Oram Syndrome.

PMID- 26195996
TI  - Primary Sjogrens Syndrome in a Child.

PMID- 26195997
TI  - Clinical Presentations of Cystic Fibrosis in Iranian Children.

PMID- 26195998
TI  - Lifesaving Vertebral Artery Stenting in a Child With Takayasu Arteritis.

PMID- 26195999
TI  - Presence of a Juvenile Idiopathic Arthritis and Chronic Granulomatous Disease in
      a Child.

PMID- 26196000
TI  - Efficacy of Preoperative Chemotherapy in Treatment of Children With Wilms' Tumor:
      A Meta-Analysis.
AB  - CONTEXT: To assess the efficacy of preoperative chemotherapy in Wilms' tumor
      patients and explore its true value for specific subgroups. OBJECTIVES: In the
      presence of these controversies, a meta-analysis that examines the efficacy of
      preoperative chemotherapy in Wilms' tumor patients and specific subgroups is
      needed to clarify these issues. The objective of this meta-analysis is to assess
      the efficacy of preoperative chemotherapy in Wilms' tumor patients and explore
      its true value for specific subgroups. DATA SOURCES: Computer-based systematic
      search with "preoperative chemotherapy", "Neoadjuvant Therapy" and "Wilms' tumor"
      as search terms till January 2013 was performed. STUDY SELECTION: No language
      restrictions were applied. Searches were limited to randomized clinical trials
      (RCTs) or retrospective studies in human participants under 18 years. A manual
      examination of references in selected articles was also performed. DATA
      EXTRACTION: Relative Risk (RR) and their 95% Confidence Interval (CI) for Tumor
      Shrinkage (TS), total Tumor Resection (TR), Event-Free Survival (EFS) and details
      of subgroup analysis were extracted. Meta-analysis was carried out with the help
      of the software STATA 11.0. Finally, four original Randomized Clinical Trials
      (RCTs) and 28 retrospective studies with 2375 patients were included. RESULTS:
      For preoperative chemotherapy vs. up-front surgery (PC vs. SU) group, the pooled
      RR was 9.109 for TS (95% CI: 5.109 - 16.241; P < 0.001), 1.291 for TR (95% CI:
      1.124 - 1.483; P < 0.001) and 1.101 for EFS (95% CI: 0.980 - 1.238; P = 0.106).
      For subgroup short course vs. long course (SC vs. LC), the pooled RR was 1.097
      for TS (95% CI: 0.784 - 1.563; P = 0.587), 1.197 for TR (95% CI: 0.960 - 1.493; P
      = 0.110) and 1.006 for EFS (95% CI: 0.910 - 1.250; P = 0.430). CONCLUSIONS: Short
      course preoperative chemotherapy is as effective as long course and preoperative
      chemotherapy only benefits Wilms' tumor patients in tumor shrinkage and resection
      but not event-free survival.

PMID- 26196001
TI  - Evaluation of Calretinin as a New Marker in the Diagnosis of Hirschsprung
      Disease.
AB  - BACKGROUND: Hirschsprung's disease (HD) is a congenital intestinal motility
      disorder with absence of ganglion cells in the colonic wall. Diagnosis of the
      disease is mainly based on the identification of the lack of ganglion cells in
      the pathology sections of the colon which is very difficult and time consuming
      and also needs several serial cut sections. There are many proposed markers in
      this field in the literature but none of them has been satisfactory. Calretinin
      immunohistochemistry (IHC) has been introduced as a new diagnostic marker to
      overcome the problems in diagnosis of this disease about 5 years ago. However
      there are few studies regarding the benefits and pitfalls of this marker.
      OBJECTIVES: The aim of this study is to determine the diagnostic value of
      calretinin IHC in detecting aganglionosis (HD). PATIENTS AND METHODS: 27 HD
      patients and 28 non-Hirschsprung's disease (NHD) patients were collected in a
      prospective study and calretinin IHC was performed on 31 aganglionic and 51
      normoganglionic full wall thickness sections of colectomies (some of the cases
      had more than 1 section). The IHC slides were evaluated by two pathologists and
      the diagnostic value was calculated in comparison with gold standard which is the
      presence or absence of ganglion cells in serial Hematoxylin and Eosin (HE)
      stained sections of the colectomies. RESULTS: There was great concordance between
      the final diagnosis of both pathologists and gold standard (k > 0.9). Calretinin
      immunostaining showed 100% specificity and positive predictive value and more
      than 90% sensitivity and negative predictive value. High agreement was present
      between the two pathologists (k > 0.9). CONCLUSIONS: Calretinin IHC is a very
      convenient, useful and valuable method to demonstrate aganglionosis in HD
      patients. Loss of calretinin immunostaining in lamina propria and submucosa is
      characteristic of HD.

PMID- 26196003
TI  - A Case of Cystic Fibrosis With a Rare Mutation (3849 + 10 kbC > T) and Normal
      Sweat Chloride Levels.

PMID- 26196002
TI  - Aortic Intima-Media Thickness and Mean Platelet Volume in Children With Type 1
      Diabetes Mellitus.
AB  - BACKGROUND: Diabetes mellitus type 1 is the most common endocrine metabolic
      disorder occurring in childhood and adolescence due to the autoimmune destruction
      of pancreatic beta cells as a result of various environmental factors interacting
      with an underlying genetic predisposition. Diabetes is a risk factor for early
      onset atherosclerosis, and the high mortality rate seen in these patients is
      partially related to cardiovascular diseases. OBJECTIVES: This study was
      conducted to compare mean platelet volume as a marker of early atherosclerosis
      with aortic intima-media thickness in children with type 1 diabetes and to
      identify its correlation with known cardiovascular risk factors. PATIENTS AND
      METHODS: The study included 27 patients between age range of 6 and 17 years that
      were diagnosed with type 1 diabetes and 30 healthy children of the same age range
      who did not have any chronic disease. In both groups, we used the color Doppler
      ultrasound to measure children's aortic intima-media thickness and identify their
      mean platelet volumes. RESULTS: There was no significant difference between the
      groups regarding gender distribution, age, High-Density Lipoprotein (HDL) and Low
      Density Lipoprotein (LDL) cholesterol levels (P > 0.05). Also no significant
      difference could be documented between the patient and control groups regarding
      the aortic intima-media thickness and mean platelet volume (P > 0.05). However,
      there was a significant correlation between aortic intima-media thickness and
      mean platelet volume (r = 0.351; P < 0.05). CONCLUSIONS: In the present study,
      there was no evidence of early atherosclerosis in children with type 1 diabetes.
      However, mean platelet volume having a significant correlation with aortic intima
      media thickness may be useful as an early marker of atherosclerosis.

PMID- 26196004
TI  - Serum Hsp70 Antigen: Early Diagnosis Marker in Perinatal Asphyxia.
AB  - BACKGROUND: Perinatal asphyxia is an important cause of mortality and permanent
      neurological and developmental deficit. Early and accurate diagnosis would help
      to establish the likely prognosis and may also help in determining the most
      appropriate treatment. Studies in experimental animal models suggest that a
      protein called Hsp70 may be a good and potentially useful marker of cellular
      stress that may be clinically useful in determining the presence of neonatal
      asphyxia. OBJECTIVES: Regarding the importance of early and accurate diagnosis of
      asphyxia, we conducted this study, which is the first investigation of the
      comparison of the serum Hsp70 antigen level between asphyxiated and healthy
      infants. PATIENTS AND METHODS: In this observational study, the serum
      concentrations of Hsp70 antigen were compared between neonates suffering from
      perinatal asphyxia (n = 50) and normal neonates (n = 51). The inclusion criteria
      for the cases were neonates who had reached term and had at least two clinical
      criteria of asphyxia. Exclusion criteria were babies with gestational age < 37
      weeks, infants with congenital abnormalities or positive blood culture. Exclusion
      criteria in this group were the requirement to hospital stay during first week of
      the life or babies whose mothers had difficulties during pregnancy or delivery.
      Term neonates without major anomalies who had asphyxia during delivery were
      enrolled in the first six hours after delivery, and control group consisted of
      healthy term neonates without problems and normal delivery process in the first
      week of life. The cord blood was taken during labor to measure Hsp70 antigen
      level by using an in-house ELISA (The enzyme-linked immunosorbent assay).
      RESULTS: The median values of serum anti Hsp70 titers were significantly higher
      in asphyxiated neonates compared with non-asphyxiated neonates (0.36 [0.04 -
      1.14] vs 0.24 [0.01 - 0.63]). At cutoff point = 0.3125 ng/mL, sensitivity was 58%
      and specificity 76% based on ROC curve. CONCLUSIONS: A significant difference
      between the serum concentrations of Hsp70 of the control and patient group was
      observed in this study. It is inferred serum concentrations of Hsp70 antigen may
      be a useful marker for the early diagnosis of that prenatal hypoxia.

PMID- 26196005
TI  - Efficacy and Safety of Using Amplatzer Ductal Occluder for Transcatheter Closure
      of Perimembranous Ventricular Septal Defect in Pediatrics.
AB  - BACKGROUND: Perimembranous Ventricular Septal Defect (PMVSD) is the most common
      subtype of ventricular septal defects. Transcatheter closure of PMVSD is a
      challenging procedure in management of moderate or large defects. OBJECTIVES: The
      purpose of this study was to show that transcatheter closure of perimembranous
      ventricular septal defect with Amplatzer Ductal Occluder (ADO) is an effective
      and safe method. PATIENTS AND METHODS: Between April 2012 and April 2013, 28
      patients underwent percutaneous closure of PMVSD using ADO. After obtaining the
      size of VSD from the ventriculogram a device at least 2 mm larger than the
      narrowest diameter of VSD at right ventricular side was chosen. The device
      deployed after confirmation of its good position by echocardiography and left
      ventriculography. Follow up evaluations were done 1 month, 6 months, 12 months
      and yearly after discharge with transthoracic echocardiography and 12 lead
      electrocardiography. RESULTS: The mean age of patients at procedure was 4.7 +/-
      6.3 (range 2 to 14) years, mean weight 14.7 +/- 10.5 (range 10 to 40) kg. The
      mean defect size of the right ventricular side was 4.5 +/- 1.6 mm. The average
      device size used was 7.3 +/- 3.2mm (range 4 to 12 mm). The ADOs were successfully
      implanted in all patients. The VSD occlusion rate was 65.7% at completion of the
      procedure, rising up to 79.5% at discharge and 96.4% during follow-up. Small
      residual shunts were seen at completion of the procedure, but they disappeared
      during follow-up in all but one patient. The mean follow-up period was 8.3 +/-
      3.6 months (range 1 to 18 months). Complete atrioventricular block (CAVB), major
      complication or death was not observed in our study. CONCLUSIONS: Transcatheter
      closure of PMVSD with ADO in children is a safe and effective treatment
      associated with excellent success and closure rates, but long-term follow-up in a
      large number of patients would be warranted.

PMID- 26196006
TI  - Flixweed vs. Polyethylene Glycol in the Treatment of Childhood Functional
      Constipation: A Randomized Clinical Trial.
AB  - BACKGROUND: Polyethylene glycol (PEG) is often considered as the first-line
      treatment for functional constipation in children. Descurainia sophia (L.) Webb
      et Berth (D. sophia) is a safe recommended medicine in Iranian folk and
      Traditional Persian Medicine for the treatment of constipation. OBJECTIVES: To
      clinically compare D. sophia with PEG 4000 (without electrolyte) in pediatric
      constipation and to assess its efficacy and side effects. PATIENTS AND METHODS:
      120 patients aged 2 - 12 years with constipation for at least 3 months were
      included in an 8 weeks lasting randomized controlled trial within two parallel
      groups. Children received either PEG, 0.4 g/kg/day, or D. sophia seeds, 2 grams
      (for children aged 2 - 4 years) and 3 grams (for those aged > 4 years) per day.
      RESULTS: A total of 109 patients completed the study (56 in D. sophia and 53 in
      PEG group). At the end of the study, 36 (64.3%) patients in D. sophia group and
      29 (54.7%) in PEG group were out of Rome III criteria (P = 0.205). Median weekly
      stool frequency in 0, 1, 2, 3 weeks of the treatment was found to be 2, 5, 5, 5
      in D. sophia and 3, 4, 4, 5 in PEG group (P = 0.139, 0.076, 0.844, 0.294),
      respectively. The number of patients who suffered flatulence was less (5, 8.9%)
      in D. sophia group as compared to PEG group (6, 11.3%) at the end of the trial (P
      = 0.461). D. sophia taste was less tolerated. CONCLUSIONS: D. sophia is
      introduced as a cheap and available medication which can be applied as a safe
      alternative to conventional PEG in the management of pediatric chronic functional
      constipation.

PMID- 26196007
TI  - Investigation of H19/RsaI Polymorphism in Children With Low Birth Weight in
      Pernambuco, Brazil.
AB  - BACKGROUND: H19 is a strong candidate gene for influencing birth weight variation
      and is exclusively imprinted maternally. In an attempt to understand the
      relationship of this gene polymorphism with low birth weight children, we
      investigated association of H19/RsaI polymorphism with low birth weight and
      normal birth weight in children and their mothers. OBJECTIVES: The aim of our
      study was to establish the association between H19 gene polymorphism and LW in
      children born in Pernambuco, state of Brazil. PATIENTS AND METHODS: It were
      selected 89 children, 40 low birth weight (LW) and 49 normal birth weight (NW)
      and 71 mothers (40 mothers of newborns NW and 31 mothers of newborns LW) attended
      at Dom Malan Hospital, Petrolina, Pernambuco - Brazil. Peripheral blood samples
      were collected from patients and genomic DNA was extracted and detected by
      electrophoresis agarose gel, stained by Blue Green Loading Dye. DNA PCR
      amplification was done using the primers H1 (sense) and H3 (antisense). PCR
      products were digested with RsaI and electrophoresed on agarose gel stained by
      ethidium bromide. Statistical analyses were performed using the program BioEstat
      version 5.0. RESULTS: The RsaI polymorphism in the H19 gene showed that genotype
      frequencies did not differ statistically between low birth weight (AA = 12.5%, AB
      = 45%, BB = 42.5%) and control (AA = 8.6% AB = 36.73%, BB= 55.10% groups) and the
      allele frequencies were not significantly different (P = 0.2897). We also did not
      observe any association between maternal H19 allele polymorphism and low birth
      weight newborns (P =0.7799) or normal birth weight children (P = 0.8976).
      CONCLUSIONS: The small size of sample may be the explanation for these results;
      future studies with more patients are needed to confirm the effect of H19/RsaI
      polymorphism on birth weight of LW newborns.

PMID- 26196008
TI  - Cayler Cardio-Facial Syndrome: An Uncommon Condition in Newborns.
AB  - INTRODUCTION: Cayler cardio-facial syndrome is a rare syndrome associated with
      asymmetric crying faces with congenital heart disease. We report a newborn that
      was diagnosed as case of Cayler Cardio-facial syndrome based on clinical features
      and was confirmed with FISH analysis. CASE PRESENTATION: A term male baby, born
      to non-consanguineous couple through normal vaginal delivery was diagnosed to
      have asymmetric crying faces with deviation of angle of mouth to left side at the
      time of birth. The baby had normal faces while sleeping or silent. Mother was
      known case of hypothyroidism and was on treatment. Baby was diagnosed as case of
      Cayler Cardio-facial Syndrome and was investigated with echocardiogram, brain
      ultrasound, total body X-ray examination, X-ray of cervico-thoracic vertebral
      column and fundus examination. Echocardiogram showed muscular VSD, brain
      ultrasound was normal and fundus examination showed tortuous retinal vessels.
      Whole body X-ray and lateral X-ray of cervico-thoracic vertebral column were not
      suggestive of any skeletal abnormalities. The other associated malformation was
      right ear microtia. Baby FISH karyotype analysis showed deletion of 22q11.2
      deletion. Baby was discharged and now on follow-up. CONCLUSIONS: Cayler syndrome
      is a rare syndrome which must be suspected if a baby has asymmetrical cry pattern
      and normal facies when baby sleeps. Patient must be evaluated with
      echocardiography to find out associated cardiac malformations. These infants
      should undergo FISH analysis for 22q11.2 deletion syndrome.

PMID- 26196009
TI  - Deflazacort Versus Prednisolone: Randomized Controlled Trial in Treatment of
      Children With Idiopathic Nephrotic Syndrome.
AB  - BACKGROUND: Corticosteroids are the main therapy of nephrotic syndrome and goal
      of corticosteroid therapy is to obtain maximum clinical benefit with minimum
      adverse effects. Children are more vulnerable to side effects of corticosteroids
      related to growth and adrenal suppression, so a search for an alternative steroid
      with fewer side-effects is underway. Deflazacort is an oxazoline derivative and
      preliminary data suggest reduced osteoporosis, lesser growth retardation and
      weight gain with deflazacort. OBJECTIVES: This study was done to compare the
      effectiveness and safety of deflazacort in idiopathic nephrotic syndrome.
      PATIENTS AND METHODS: Twenty five children with age between 2 to 12 years, with
      idiopathic nephrotic syndrome were enrolled. They were randomly assigned to
      receive deflazacort (Group A, n = 12) or prednisolone (Group B, n = 13) and were
      followed up for six months. RESULTS: All children of group A and 11 of group B
      had remission. Two children from group B were steroid resistant. Mean time taken
      to induce remission was significantly (P = 0.012) less in group A (10.25 +/- 2.41
      days) than group B (12.55 +/- 1.44 days). One patient in group A had relapse on
      follow up as compared to 3 in group B (P = 0.58). Statistically significant
      difference (P = 0.03) in change in mean height was found between group A (2.13 +/
      0.50cm) and B (1.44 +/- 0.45 cm), with group B gaining less height. CONCLUSIONS:
      Remission rate in both groups was comparable although time taken to induce
      remission was shorter in deflazacort group and there was a significant difference
      in change of mean height on follow up with prednisolone group gaining lesser
      height.

PMID- 26196010
TI  - Noncompaction in Healthy Subjects, Dilated and Hypertrophic Cardiomyopathy, and
      Neuromuscular Disorders Is the Same Entity.

PMID- 26196011
TI  - The relationship between distorted body image and lifestyle among Japanese
      adolescents: a population-based study.
AB  - BACKGROUND: Distorted body image plays a significant role in the development of
      obesity, eating problems, and eating disorders. The aim of this study was to
      investigate the relationship between distorted body image and lifestyle among
      Japanese adolescent boys and girls. METHODS: Subjects were 1731 seventh graders
      (age 12-13 years) from the Ina-town's junior high schools, Japan, from 2005-2009.
      The height and weight of each subject were measured. Childhood underweight,
      overweight, and obesity were defined using the body mass index cutoff points
      proposed by the International Obesity Task Force. Information regarding the self
      perceived weight status and lifestyles (exercise, snacking after dinner,
      breakfast, wakeup time, bedtime) of each subject was collected using a self
      administered questionnaire. Self-perceived weight status was categorized into
      three groups (thin, normal, or heavy), and compared with the subjects' actual
      weight status. Body image perception was categorized into the following three
      groups: an underestimated own weight status group (underestimated group), a
      correct own weight status group (correct group) and an overestimated own weight
      status group (overestimated group). RESULTS: The proportion of boys in the
      underestimated group was higher than that of girls, while the opposite was true
      for the overestimated group (P < 0.001). There were no statistically significant
      differences in lifestyle between the underestimated group and the correct group
      regardless of sex. In contrast, there were statistically significant differences
      between the overestimated group and the correct group in the lifestyle factors of
      exercise among boys and snacking after dinner among girls. The adjusted odds
      ratio (OR) in boys who exercised daily significantly decreased (OR: 0.35, 95 %
      CI: 0.16-0.77), while a significantly increased OR was observed in girls who
      snacked after dinner (OR: 1.53, 95 % CI: 1.07-2.19). CONCLUSION: Adolescent boys
      tended to underestimate their body weight, whereas adolescent girls were likely
      to overestimate their body weight. Furthermore, lifestyle factors associated with
      distorted body image differed by sex, with exercise affecting body image
      perception among boys and snacking after dinner affecting body image perception
      among girls. Thus, lifestyle may lead to distorted body image among adolescents.

PMID- 26196012
TI  - Myeloid derived suppressor and dendritic cell subsets are related to clinical
      outcome in prostate cancer patients treated with prostate GVAX and ipilimumab.
AB  - BACKGROUND: Cancer-related disturbances in myeloid lineage development, marked by
      high levels of myeloid-derived suppressor cells (MDSC) and impaired dendritic
      cell (DC) development, are associated with poor clinical outcome due to immune
      escape and therapy resistance. Redressing this balance may therefore be of
      clinical benefit. Here we investigated the effects of combined Prostate
      GVAX/ipilimumab immunotherapy on myeloid subsets in peripheral blood of
      castration-resistant prostate cancer (CRPC) patients as well as the putative
      predictive value of baseline and on-treatment myeloid parameters on clinical
      outcome. METHODS: Patients with CRPC (n = 28) received thirteen intradermal
      administrations of Prostate GVAX, consisting of two allogeneic GM-CSF-transduced
      and irradiated prostate cancer cell lines (LN-CaP and PC3) and six infusions of
      escalating doses of anti-CTLA4/ipilimumab. Frequencies and activation status of
      peripheral blood DC (PBDC) and MDSC were determined before, during and after
      treatment by flowcytometric analysis and related to clinical benefit. RESULTS:
      Significant treatment-induced activation of conventional and plasmacytoid DC
      subsets (cDC and pDC) was observed, which in the case of BDCA1/CD1c(+) cDC1 and
      MDC8(+)/6-sulfoLacNAc(+) inflammatory cDC3 was associated with significantly
      prolonged overall survival (OS), but also with the development of autoimmune
      related adverse events. High pre-treatment levels of CD14(+)HLA-DR(-)monocytic
      MDSC (mMDSC) were associated with reduced OS. Unsupervised clustering of these
      myeloid biomarkers revealed particular survival advantage in a group of patients
      with high treatment-induced PBDC activation and low pretreatment frequencies of
      suppressive mMDSC in conjunction with our previously identified lymphoid
      biomarker of high pretreatment CD4(+)CTLA4(+) T cell frequencies. CONCLUSIONS:
      Our data demonstrate that DC and MDSC subsets are affected by prostate
      GVAX/ipilimumab therapy and that myeloid profiling may contribute to the
      identification of patients with possible clinical benefit of Prostate
      GVAX/ipilimumab treatment.

PMID- 26196013
TI  - Preclinical evaluation of SMM-189, a cannabinoid receptor 2-specific inverse
      agonist.
AB  - Cannabinoid receptor 2 agonists and inverse agonists are emerging as new
      therapeutic options for a spectrum of autoimmune-related disease. Of particular
      interest, is the ability of CB2 ligands to regulate microglia function in
      neurodegenerative diseases and traumatic brain injury. We have previously
      reported the receptor affinity of 3',5'-dichloro-2,6-dihydroxy-biphenyl-4-yl)
      phenyl-methanone (SMM-189) and the characterization of the beneficial effects of
      SMM-189 in the mouse model of mild traumatic brain injury. Herein, we report the
      further characterization of SMM-189 as a potent and selective CB2 inverse
      agonist, which acts as a noncompetitive inhibitor of CP 55,940. The ability of
      SMM-189 to regulate microglial activation, in terms of chemokine expression and
      cell morphology, has been determined. Finally, we have determined that SMM-189
      possesses acceptable biopharmaceutical properties indicating that the triaryl
      class of CB2 inverse agonists are viable compounds for continued preclinical
      development for the treatment of neurodegenerative disorders and traumatic brain
      injury. 

PMID- 26196014
TI  - Routine diversion of patients with STEMI to high-volume PCI centres: modelling
      the financial impact on referral hospitals.
AB  - OBJECTIVE: To quantify possible revenue losses from proposed ST-elevation
      myocardial infarction (STEMI) patient diversion policies for small hospitals that
      lack high-volume percutaneous coronary intervention (PCI) capability status (ie,
      'STEMI referral hospitals'). BACKGROUND: Negative financial impacts on STEMI
      referral hospitals have been discussed as an important barrier to implementing
      regional STEMI bypass/transfer protocols. However, there is little empirical data
      available that directly quantifies this potential financial impact. METHODS:
      Using detailed financial charges from Florida hospital discharge data, we
      examined the potential negative financial impact on 112 STEMI referral hospitals
      from losing all inpatient STEMI revenue. The main outcome was projected revenue
      loss (PRL), defined as total annual patient with STEMI charges as a proportion of
      total annual charges for all patients. We hypothesised that for most community
      hospitals (>90%), STEMI revenue represented only a small fraction of total
      revenue (<1%). We further examined the financial impact of the 'worst case'
      scenario of loss of all acute coronary syndrome (ACS) (ie, chest pain) patients.
      RESULTS: PRLs were $0.33 for every $100 of patient revenue statewide for STEMI
      and $1.73 for ACS. At the individual hospital level, the 90th centile PRL was
      $0.74 for STEMI and $2.77 for ACS. PRLs for STEMI were not greater in rural areas
      compared with major metropolitan areas. Hospital revenue centres that would be
      most impacted by loss of patients with STEMI were cardiology procedures and
      intensive care units. CONCLUSIONS: Loss of patient with STEMI revenues would
      result in only a small financial impact on STEMI referral hospitals in Florida
      under proposed STEMI diversion/rapid transfer protocols. However, spillover loss
      of patients with ACS would increase revenue loss for many hospitals.

PMID- 26196015
TI  - The ischaemic constellation: an alternative to the ischaemic cascade-implications
      for the validation of new ischaemic tests.
AB  - The ischaemic cascade is the concept that progressive myocardial oxygen supply
      demand mismatch causes a consistent sequence of events, starting with metabolic
      alterations and followed sequentially by myocardial perfusion abnormalities, wall
      motion abnormalities, ECG changes, and angina. This concept would suggest that
      investigations that detect expressions of ischaemia earlier in the cascade should
      be more sensitive tests of ischaemia than those that detect expressions appearing
      later in the cascade. However, careful review of the studies on which the
      ischaemic cascade is based suggests that the ischaemic cascade concept may be
      less well supported by the literature than assumed. In this review we explore
      this, discuss an alternative method for conceptualising ischaemia, and discuss
      the potential implications of this new approach to clinical studies and clinical
      practice. 

PMID- 26196016
TI  - Single-centre cohort study of gender influence in coronary CT angiography in
      patients with a low to intermediate pretest probability of coronary heart
      disease.
AB  - BACKGROUND: In 'real-world' patient populations undergoing coronary CT
      angiography (CCTA), it is unclear whether a correlation exists between gender,
      coronary artery calcium (CAC) score and subsequent referral for invasive coronary
      angiography and coronary revascularisation. We therefore investigated the
      relationship between gender, CAC and use of subsequent invasive coronary
      angiography and coronary revascularisation in a cohort of patients with chest
      discomfort and low to intermediate pretest probability of coronary artery disease
      who underwent a CCTA at our diagnostic centre. METHODS: This is a cohort study
      that included patients examined between 2010 and 2013. Data were obtained from
      the Western Denmark Heart Registry. The follow-up ended 11 March 2014. RESULTS: A
      total of 3541 people (1621 men and 1920 women) were examined by CCTA. The rate of
      invasive coronary angiography during follow-up was 28.5% in men versus 18.3% in
      women (p<0.001). The rate of coronary revascularisation during follow-up was
      11.4% in men versus 5.1% in women (p<0.001). The CAC-adjusted HR in women versus
      men was 0.98 (95% CI 0.85 to 1.13) for invasive coronary angiography and 0.73
      (95% CI 0.57 to 0.93) for coronary revascularisation. Further adjustment for age
      and other risk factors did not change these estimates. CONCLUSIONS: Women had a
      lower CAC score than men and a corresponding lower rate of invasive coronary
      angiography. The risk of coronary revascularisation was modestly reduced in
      women, irrespective of CAC. This may reflect a gender-specific difference in
      coping with chest discomfort, gender-specific referral bias for CCTA, and/or a
      gender-specific difference in the balance between coronary calcification and
      obstructive coronary heart disease.

PMID- 26196017
TI  - Treatment choices in elderly patients with ST: elevation myocardial infarction
      insights from the Vital Heart Response registry.
AB  - BACKGROUND: Management of elderly patients with ST elevation myocardial
      infarction (STEMI) is challenging and they are under-represented in trials.
      Accordingly, we analysed reperfusion strategies and their effectiveness in
      patients with STEMI >=75 years compared to <75 years within a comprehensive
      inclusive registry. METHODS: Consecutive patients with STEMI admitted to hospital
      and tracked within a regional registry (2006-2011) were analysed comparing
      reperfusion strategy (primary percutaneous coronary intervention (PPCI),
      fibrinolysis and no reperfusion) between patients >=75 vs <75 years old as well
      as across the reperfusion strategies in those >=75 years. RESULTS: There were
      3588 patients with STEMI with 646 (18%) >=75 years old. Elderly patients were
      more likely female (46.9% vs 18.4%) and had more prior: angina (28.2% vs 17.2%),
      myocardial infarction (MI; 22.8% vs 13.9%), hypertension (67.6% vs 44.2%), heart
      failure (2.3% vs 0.3%) and atrial fibrillation (2.2% vs 0.5%) (all p<0.001). The
      reperfusion strategy for patients >=75 vs <75: PPCI 45.3% vs 41.2%, fibrinolysis
      24.8% vs 45.7%, and no reperfusion 29.9% vs 13.1% (p<0.001). Time from symptoms
      to first medical contact (median, 93 vs 78 min p=0.008) and PPCI (median, 166 vs
      136 min (p<0.001) were longer for >=75 years. In those >=75 years outcomes by
      reperfusion (PPCI, fibrinolysis and none) were: in-hospital death 13.3%, 9.4% and
      19.7% (p=0.018), and composite of death, recurrent-MI, cardiogenic shock and
      congestive heart failure 28%, 20% and 33.2% (p=0.022). CONCLUSIONS: Elderly
      patients have more comorbidities, worst in-hospital clinical outcomes and are
      less likely to receive reperfusion. Acknowledging physician selection of the
      reperfusion strategy; outcomes appear favourable in the elderly receiving
      fibrinolysis.

PMID- 26196018
TI  - Does valvuloarterial impedance impact prognosis after surgery for severe aortic
      stenosis in the elderly?
AB  - BACKGROUND: Valvuloarterial impedance (Zva) was introduced as a prognostic
      measure in patients with aortic stenosis (AS). However, it is unclear whether Zva
      has a prognostic impact on survival after surgical aortic valve replacement (AVR)
      in patients with severe AS with preserved ejection fraction (EF). METHODS: We
      retrospectively reviewed 929 consecutive patients who had AVR. We investigated
      170 elderly patients (age >65 years, mean 76 years) who had AVR secondary to
      severe AS (mean gradient >=40 mm Hg; aortic valve area <=1 cm(2); peak velocity
      >=4 m/s). Patients with EF <50%, greater than moderate aortic regurgitation,
      prior heart surgery and concomitant mitral or tricuspid valve surgery were
      excluded. Zva was calculated and the patients were divided into two groups; low
      Zva, Zva <4.3 (n=82) and high Zva, Zva >=4.3 (n=88). The end point was all-cause
      of death. Survival curves were calculated according to Kaplan-Meier method.
      RESULTS: Age, prevalence of hypertension, diabetes, chronic kidney disease (CKD),
      atrial fibrillation, symptoms, EF, E/e' and concomitant coronary artery bypass
      graft were not different between the groups. Survival was not different between
      the groups at 5 years (70% in low Zva and 81% in high Zva; p=0.21) and for the
      entire follow-up period (p=0.23). Only age was a significant factor in predicting
      survival by multivariate analyses in Cox proportional hazards model after
      adjusting for Zva, CKD, atrial fibrillation and hypertension. CONCLUSIONS: Our
      results suggest that preoperative Zva does not have a prognostic impact on
      postoperative survival in elderly patients with severe AS with preserved EF.
      Further investigation is needed to elucidate the controversial results.

PMID- 26196019
TI  - Fetuin-A is related to infarct size, left ventricular function and remodelling
      after acute STEMI.
AB  - OBJECTIVE: To investigate the relationship between plasma fetuin-A, an anti
      inflammatory glycoprotein which might be involved in myocardial healing after
      acute infarction, and infarct size, left ventricular (LV) function and dimensions
      as well as the occurrence of adverse remodelling at 4 months after acute ST
      segment elevation myocardial infarction (STEMI). METHODS: In this single-centre
      prospective, observational study, 89 patients underwent cardiac MR within the
      first week and 4 months after mechanical reperfusion for first STEMI. Infarct
      size, LV function and dimensions were assessed at both time points. Fetuin-A
      levels were determined from blood samples drawn at a median of 49 h (IQR 30-59 h)
      after STEMI by an immunofluorescent assay. RESULTS: Fetuin-A levels (median 568
      ug/mL, IQR 478-763 ug/mL) were significantly correlated with infarct size and LV
      ejection fraction at baseline and follow-up (all p<0.05). Moreover, fetuin-A was
      related to the increase in the end-diastolic volume index (r=-0.383, p<0.001).
      According to multivariate logistic regression analysis, fetuin-A concentrations
      (HR=0.17, 95% CI 0.03 to 0.89, p=0.036) besides the presence of late
      microvascular obstruction (HR=10.03, 95% CI 0.98 to 102.43, p=0.05) were
      significantly related to the occurrence of adverse LV remodelling at 4 months.
      CONCLUSIONS: Circulating fetuin-A at day 2 after STEMI is related to acute and
      chronic infarct size, LV function and dimensions. In addition, it might be useful
      to identify patients at increased risk for adverse LV remodelling.

PMID- 26196020
TI  - Effect of the adult pneumococcal polysaccharide vaccine on cardiovascular
      disease: a systematic review and meta-analysis.
AB  - Animal models and clinical studies suggest a mechanistic link between the
      pneumococcal polysaccharide vaccine (PPV) and a cardiovascular protective effect.
      However, conflicting results exist from several large observational studies in
      humans. We set out to systematically review current literature and conduct meta
      analyses of studies on PPV and cardiovascular outcomes. Medline, Embase and
      CENTRAL were searched for randomised controlled trials (RCTs) and observational
      studies in adults, using PPV as the intervention, up to 30 April 2014. Studies
      that compared PPV with a control (another vaccine, no vaccine or placebo) and
      recorded ischaemic events were included in this review. Two investigators
      extracted data independently on study design, baseline characteristics and
      summary outcomes. Study quality was examined using the Newcastle-Ottawa Quality
      Assessment Scale. Pooled estimates using random effects models and their 95% CIs
      were calculated separately for the outcomes of acute coronary syndrome (ACS)
      events and stroke. No RCT data were available. A total of 230 426 patients were
      included in eight observational studies and recorded as ACS events. PPV was
      associated with significantly lower odds of ACS events in patients 65 years and
      older (pooled OR=0.83 (95% CI 0.71 to 0.97), I(2)=77.0%). However, there was no
      significant difference in ACS events when younger people were included (pooled
      OR=0.86 (95% CI 0.73 to 1.01), I(2)=81.4%). Pooling of four studies, covering a
      total of 192 210 patients, did not find a significantly reduced risk of stroke in
      all patients (pooled OR=1.00 (95% CI 0.89 to 1.12), I(2)=55.3%), or when
      restricted to those 65 years and older (pooled OR=0.96 (95% CI 0.87 to 1.05),
      I(2)=22.5%). In this meta-analysis of observational studies, the use of PPV was
      associated with a significantly lower risk of ACS events in the older population,
      but not stroke. An adequately powered and blinded RCT to confirm these findings
      is warranted. 

PMID- 26196021
TI  - Incidence of cardiovascular events and gastrointestinal bleeding in patients
      receiving clopidogrel with and without proton pump inhibitors: an updated meta
      analysis.
AB  - BACKGROUND: Dual antiplatelet therapy is the standard of care after coronary
      stent placement but increases the bleeding risk. The effects of proton pump
      inhibitors (PPIs) on clopidogrel metabolism have been described, but the clinical
      significance is not yet definitive. We aimed to do an updated meta-analysis
      comparing outcomes in patients receiving clopidogrel with and without PPIs.
      METHODS: We systematically searched PubMed, Scopus and the Cochrane Central
      Register of Controlled Trials for randomised controlled trials (RCTs) and
      controlled observational studies in patients taking clopidogrel stratified by
      concomitant PPI use. Heterogeneity was examined with the Cochran Q test and I(2)
      statistics; p values inferior to 0.10 and I(2) >25% were considered significant
      for heterogeneity. RESULTS: We included 39 studies with a total of 214 851
      patients, of whom 73 731 (34.3%) received the combination of clopidogrel and a
      PPI. In pooled analysis, all-cause mortality, myocardial infarction, stent
      thrombosis and cerebrovascular accidents were more common in patients receiving
      both drugs. However, among 23 552 patients from eight RCTs and propensity-matched
      studies, there were no significant differences in mortality or ischaemic events
      between groups. The use of PPIs in patients taking clopidogrel was associated
      with a significant reduction in the risk of gastrointestinal bleeding.
      CONCLUSIONS: The results of our meta-analysis suggest that PPIs are a marker of
      increased cardiovascular risk in patients taking clopidogrel, rather than a
      direct cause of worse outcomes. The pharmacodynamic interaction between PPIs and
      clopidogrel most likely has no clinical significance. Furthermore, PPIs have the
      potential to decrease gastrointestinal bleeding in clopidogrel users.

PMID- 26196022
TI  - An optimized TALEN application for mutagenesis and screening in Drosophila
      melanogaster.
AB  - Transcription activator-like effector nucleases (TALENs) emerged as powerful
      tools for locus-specific genome engineering. Due to the ease of TALEN assembly,
      the key to streamlining TALEN-induced mutagenesis lies in identifying efficient
      TALEN pairs and optimizing TALEN mRNA injection concentrations to minimize the
      effort to screen for mutant offspring. Here we present a simple methodology to
      quantitatively assess bi-allelic TALEN cutting, as well as approaches that permit
      accurate measures of somatic and germline mutation rates in Drosophila
      melanogaster. We report that percent lethality from pilot injection of candidate
      TALEN mRNAs into Lig4 null embryos can be used to effectively gauge bi-allelic
      TALEN cutting efficiency and occurs in a dose-dependent manner. This timely Lig4
      dependent embryonic survival assay also applies to CRISPR/Cas9-mediated
      targeting. Moreover, the somatic mutation rate of individual G0 flies can be
      rapidly quantitated using SURVEYOR nuclease and capillary electrophoresis, and
      germline transmission rate determined by scoring progeny of G0 outcrosses.
      Together, these optimized methods provide an effective step-wise guide for
      routine TALEN-mediated gene editing in the fly.

PMID- 26196023
TI  - Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in
      membrane domains transport and homeostasis.
AB  - Biological membranes in eukaryotes contain a large variety of proteins and lipids
      often distributed in domains in plasma membrane and endomembranes. Molecular
      mechanisms responsible for the transport and the organization of these membrane
      domains along the secretory pathway still remain elusive. Here we show that
      vesicular SNARE TI-VAMP/VAMP7 plays a major role in membrane domains composition
      and transport. We found that the transport of exogenous and endogenous GPI
      anchored proteins was altered in fibroblasts isolated from VAMP7-knockout mice.
      Furthermore, disassembly and reformation of the Golgi apparatus induced by
      Brefeldin A treatment and washout were impaired in VAMP7-depleted cells,
      suggesting that loss of VAMP7 expression alters biochemical properties and
      dynamics of the Golgi apparatus. In addition, lipid profiles from these knockout
      cells indicated a defect in glycosphingolipids homeostasis. We conclude that
      VAMP7 is required for effective transport of GPI-anchored proteins to cell
      surface and that VAMP7-dependent transport contributes to both sphingolipids and
      Golgi homeostasis.

PMID- 26196024
TI  - Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal
      Infections (PANDAS): Experience at a Tertiary Referral Center.
AB  - BACKGROUND: Pediatric autoimmune neuropsychiatric disorder associated with
      streptococcal infections (PANDAS) is an autoimmune disorder presenting with
      obsessive compulsive disorder and/or tics. Like Sydenham's chorea, its presumed
      pathogenesis consists of autoantibodies cross-reacting with neurons in response
      to a group A beta-hemolytic streptococcal infection (GASI). There are currently
      no diagnostic laboratory findings and management ranges from antibiotic
      prophylaxis to intravenous immunoglobulin to plasmapheresis. The diagnosis
      remains controversial, resulting in inconsistent referrals and significant
      patient anxiety. METHODS: A retrospective study was performed on all patients
      referred to the Pediatric Infectious Disease Division with a pre-referral
      diagnosis of PANDAS. Patients were analyzed by demographics, medical history, co
      morbidities, symptoms, prior treatment, laboratory tests, management strategies,
      and treatment outcomes. RESULTS: From 2003 to 2013, there were 21 patients with a
      pre-referral diagnosis of PANDAS. Only five met the diagnostic criteria. No
      patient at referral had an objective scale to monitor symptoms. Eight referrals
      had a major psychiatric disorder, and none fulfilled diagnostic criteria
      (p<0.01). DISCUSSION: The majority of the patients referred with a pre-diagnosis
      of PANDAS do not fulfill diagnostic criteria nor do they have objective criteria
      for symptom monitoring. Major psychiatric disorders do not seem to be associated
      with PANDAS, and better physician education may prevent misdiagnoses.
      Multidisciplinary management is recommended.

PMID- 26196025
TI  - Benign Hereditary Chorea: An Update.
AB  - Benign hereditary chorea (BHC) is a childhood-onset, hyperkinetic movement
      disorder normally with little progression of motor symptoms into adult life. The
      disorder is caused by mutations to the NKX2.1 (TITF1) gene and also forms part of
      the "brain-lung-thyroid syndrome", in which additional developmental
      abnormalities of lung and thyroid tissue are observed. In this review, we
      summarize the main clinical findings in "classical" BHC syndrome and discuss more
      recently reported atypical features, including non-choreiform movement
      phenotypes. We highlight additional non-motor characteristics such as cognitive
      impairment and psychiatric symptoms, while discussing the evidence for BHC as a
      developmental disorder involving impaired neural migration and other multisystem
      developmental abnormalities. Finally, we will discuss the efficacy of available
      therapies in both affected pediatric and adult cohorts. Delineation of the BHC
      disease spectrum will no doubt expand our understanding of this disorder,
      facilitating better targeting of genetic testing and establish a framework for
      future clinical trials. 

PMID- 26196026
TI  - PLA2G6-associated Dystonia-Parkinsonism: Case Report and Literature Review.
AB  - BACKGROUND: Phospholipase-associated neurodegeneration (PLAN) caused by PLA2G6
      mutations is a recessively inherited disorder with three known phenotypes: the
      typical infantile onset neuroaxonal dystrophy (INAD); an atypical later onset
      form (atypical NAD); and the more recently recognized young-onset dystonia
      parkinsonism (PLAN-DP). CASE REPORT: We report the clinical, radiological, and
      genetic findings of a young Pakistani male with PLAN-DP. We review 11 previously
      published case reports cited in PubMed, and summarize the demographic, clinical,
      genetic, and radiological data of the 23 patients described in those articles.
      DISCUSSION: PLAN-DP presents with diverse motor, autonomic, and neuropsychiatric
      features and should be considered in the differential diagnosis of patients with
      young-onset neurodegenerative disorders.

PMID- 26196027
TI  - Comparison of VIM and STN DBS for Parkinsonian Resting and Postural/Action
      Tremor.
AB  - BACKGROUND: Resting tremor is common in Parkinson's disease (PD), but up to 47%
      of PD patients have action tremor, which is sometimes resistant to medications.
      Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the
      thalamus or subthalamic nucleus (STN) is effective for medication-refractory
      tremor in PD, though it remains unclear whether STN DBS is as effective as VIM
      DBS for postural/action tremor related to PD. METHODS: We carried out a single
      center retrospective review of patients with medication-refractory resting,
      postural, and action PD tremor, treated with either VIM or STN DBS between August
      2004 and March 2014. We assessed the degree of improvement using items 20 and 21
      of the Unified Parkinson's Disease Rating Scale (UPDRS) motor scale and examined
      the proportion of patients achieving tremor arrest. RESULTS: A total of 18
      patients were analyzed, 10 treated with STN and eight treated with VIM, with
      similar off-medication motor UPDRS scores. There was no significant difference in
      improvement in tremor scores or in the proportion of patients experiencing tremor
      arrest between the two stimulation sites. Overall, 56% and 72% of patients
      experienced complete absence of postural/action tremor and resting tremor,
      respectively, at last follow-up. DISCUSSION: This study demonstrated excellent
      outcomes on both resting and postural/action tremor after either VIM or STN DBS.
      Resting tremor improved to a greater degree than postural/action tremor in both
      groups. These results suggest that a large randomized controlled trial is needed
      to show a superior effect of one target on PD tremor.

PMID- 26196028
TI  - PANDAS: The Need to Use Definitive Diagnostic Criteria.
AB  - In Response to: Helm CE, Blackwood RA. Pediatric autoimmune neuropsychiatric
      disorder associated with streptococcal infections (PANDAS): Experience at a
      tertiary referral center. Tremor Other Hyperkinet Mov. 2015; 5. doi:
      10.7916/D8348JCX. 

PMID- 26196029
TI  - Posterior lumbar interbody fusion with instrumented posterolateral fusion in
      adult spondylolisthesis: description and association of clinico-surgical
      variables with prognosis in a series of 36 cases.
AB  - BACKGROUND: We present our experience in the treatment of patients with isthmic
      or degenerative spondylolisthesis, by means of a posterior lumbar interbody
      fusion (PLIF) and instrumented posterolateral fusion (IPLF), and we compare them
      with those published in the literature. We analyse whether there exists any
      statistical association between the clinical characteristics of the patient,
      radiological characteristics of the disease and our surgical technique, with the
      complications and the clinical-radiological prognosis of the cases. METHOD: We
      designed a prospective study. A total of 36 cases were operated. The patients
      included were 14 men and 22 women, with an average age of 57.17+/-27.32 years.
      Our technique consists of PLIF+IPLF, using local bone for the fusion. The
      clinical results were evaluated with the Visual Analogical Scale (VAS) and the
      Kirkaldy-Willis criteria. The radiological evaluation followed the Bratingan
      (PLIF) and Lenke (IPLF) methodology. A total of 42 variables were statistically
      analysed by means of SPSS18. We used the Paired Student's T-test, logistic
      regression and Pearson's Chi-square-test. RESULTS: The spondylolisthesis was
      isthmic in 15 cases and degenerative in 21 cases. The postoperative evaluations
      had excellent or good results in 94.5% (n = 34), with a statistically significant
      improvement in the back pain and sciatica (p < 0.01). The rate of circumferential
      fusion reached was approximately 92%. We had 13.88% of transitory morbility and
      0% of mortality associated with our technique. A greater age, degree of listhesis
      or length of illness before the intervention, weakly correlated with worse
      clinical results (p< -0.2). In our series, the logistical regression showed that
      the clinical characteristics of the patient, radiological characteristics of the
      lesion and our surgical technique were not associated with greater postoperative
      complications. CONCLUSION: Although a higher level of training is necessary, we
      believe that the described technique is a very effective decision in cases of
      spondylolisthesis, isthmic or degenerative, refractory to conservative treatment,
      for the obtaining the best clinical results and rates of fusion, with similar
      risks to those of the other published techniques. Our statistical analysis could
      contribute to improve outcomes after surgery.

PMID- 26196030
TI  - Comparison Between Gearshift And Drill Techniques For Pedicle Screw Placement By
      Resident Surgeons.
AB  - BACKGROUND: Various techniques have been described for pedicle screw placement
      with established clinical and radiological success. Suboptimal screw trajectories
      can compromise bony purchase and, worse yet, cause neurological and vascular
      injuries. Thus, it is of paramount importance to achieve maximum accuracy of
      screw placement. Our objective is to evaluate the accuracy of pedicle screw
      placement in the thoracolumbar spine by resident surgeons. Two popular
      techniques, gearshift versus drill, were compared. METHODS: This is a a cadaveric
      surgical technique comparison study. Six resident surgeons instrumented the spine
      from T1 to S1 using both gearshift and drill techniques. Each pedicle was
      randomly assigned to either of the techniques. Pedicle screws were placed
      freehand without radiographic guidance. Violations (medial, lateral, anterior,
      superior and inferior) were recorded by studying the computerized tomographic
      scans of instrumented cadavers by blinded observers. Critical perforations were
      defined as greater than 2mm breach of the pedicle wall. RESULTS: A total of 100
      vertebrae (200 pedicles) were instrumented in the six cadavers. 103 pedicles were
      breached (51.5% of total pedicles). Lateral violations were the most encountered
      (65% of violations, 67 total, 48 critical, 19 noncritical) followed by medial
      (24%, 25 total, 13 critical, 12 noncritical), and the rest were anterior (3%),
      superior (4%) and inferior (4%). There was no overall difference in violations
      comparing the gearshift technique (49.5%, 51 total, 37 critical, 14 noncritical)
      with drill technique (50.5%, 52 total, 33 critical, 19 noncritical). Analyzing
      the breaches at individual vertebra indicated most violations at T6 (11), T5
      (10), followed by T3 (9) and T4 (9), decreasing towards the lumbosacral
      vertebrae. CONCLUSION: The results of this study suggest that the gearshift and
      drill techniques for placement of pedicle screws in the thoracolumbar spine fare
      similarly with regards to risk of breach when applied by resident surgeons.

PMID- 26196031
TI  - Perioperative Risks Associated with Cervical Spondylotic Myelopathy Based on
      Surgical Treatment Strategies.
AB  - BACKGROUND: Few studies have provided nationwide estimates of patient
      characteristics and procedure-related complications, or examined postsurgical
      outcomes for patients with cervical spondylotic myelopathy (CSM) comparatively
      with respect to surgical approach. The objective of this study is to identify
      patients at risk for morbidity and mortality directly related with the selected
      approach, report an overall nation-wide complication rate for each approach
      against which surgeons can compare themselves, and direct future research to
      improve patient outcomes. METHODS: Patients surgically treated for CSM were
      retrospectively identified using ICD-9-CM codes from the Nationwide Inpatient
      Sample (NIS) database. Four cohorts were compared for demographics and hospital
      system-related data: anterior (ACDF, ACCF), posterior decompression without
      fusion, decompression with posterior fusion, and combined anterior-posterior.
      Multivariate analysis was also used to determine the odds ratio of morbidity and
      mortality among the cohorts. RESULTS: 54,416 discharges were identified between
      2001 and 2010: 34,400 anterior, 9,014 decompression procedures without fusion,
      8,741 decompression procedures with posterior fusion, and 2,261 combined anterior
      posterior. Groups were statistically different with respect to age, length of
      hospital stay, mortality, and complications. Groups were statistically different
      for Deyo score except between posterior decompression only and combined
      approaches. Using multivariate analysis and adjusting for covariates, the
      combined (2.74[2.18-3.44]) and laminectomy (1.22[1.04-1.44]) cohorts had an
      increased risk of mortality when compared to anterior alone. CONCLUSION: These
      findings are the first to determine the rates and odds of perioperative risks
      directly related to combined anterior-posterior procedures. This study provides
      clinically useful data for surgeons to educate patients and direct future
      research to improve patient outcomes.

PMID- 26196032
TI  - Quantification of Multifidus Atrophy and Fatty Infiltration Following a Minimally
      Invasive Microdiscectomy.
AB  - BACKGROUND: Multifidus muscle degeneration and atrophy have been demonstrated
      following traditional open spine surgery. The purpose of this study was to
      quantify multifidus muscle atrophy and fatty infiltration following a 1-level
      minimally invasive (MIS) lumbar discectomy. METHODS: Magnetic resonance imaging
      (MRI) of 24 patients who underwent a primary 1-level MIS microdiscectomy were
      reviewed. Demographics, operative levels, and time from surgery to imaging were
      assessed. Total and lean cross-sectional areas (CSA), T1-signal intensity ratio
      between the multifidus and psoas muscles, and lean-to-total CSA ratio were
      measured. Pre- and postoperative values were compared within each patient
      utilizing paired sample T-tests. RESULTS: The mean age was 47.8+/-14.2 years. MRI
      was obtained 182.5+/-194.4 days following index surgery. On the ipsilateral side,
      total CSA decreased at the index level (-4.9%) and the lean CSA decreased at the
      index (-6.2%), inferior pedicle (-13.0%), and inferior disc levels (-18.6%). On
      the contralateral side, no significant decreases in total or lean CSA were
      demonstrated. T1-signal intensity ratios increased at all levels, but the
      differences were not statistically significant. The lean-to-total CSA ratio was
      decreased at the superior disc (-5.2%), inferior pedicle (-8.4%), and inferior
      disc levels (-17.2%) on the ipsilateral side and at the contralateral inferior
      disc level (-5.3%). CONCLUSIONS: Primary 1-level MIS discectomy results in
      minimal short-term atrophy and fatty infiltration of the multifidus at the index
      level. Total CSA atrophy was mainly confined to the ipsilateral side at the index
      level. Lean CSA atrophy was observed mainly at and below the index level on the
      ipsilateral side. Fatty infiltration, as measured by the lean-to-total CSA ratio,
      ranged 1.2-17.2% on the ipsilateral and 0-5.3% on the contralateral side with
      greater fat content demonstrated caudally to the surgical level. CLINICAL
      RELEVANCE: Overall, the majority of the multifidus muscle appears to be
      radiographically preserved following an MIS lumbar discectomy.

PMID- 26196033
TI  - Viscoelastic Disc Arthroplasty Provides Superior Back and Leg Pain Relief in
      Patients with Lumbar Disc Degeneration Compared to Anterior Lumbar Interbody
      Fusion.
AB  - BACKGROUND: Lumbar disc degeneration (LDD) is one of the most frequently
      diagnosed spinal diseases. The symptoms these disorders cause are anticipated to
      increase as the population in Western countries ages. PURPOSE: Compare back and
      leg pain alleviation in patients with LDD and a viscoelastic disc prosthesis
      documented in the SWISSspine registry versus patients with anterior lumbar
      interbody fusion documented in the Spine Tango registry. STUDY DESIGN:
      Prospectively collected clinical and outcome data in two independent spine
      registries. Outcome Measures were back and leg pain relief on 0 to 10 numerical
      rating scales. MATERIALS AND METHODS: The analysis included a single surgeon
      series of 48 patients with viscoelastic total disc replacement (VTDR) from the
      SWISSspine registry which were compared to 131 patients with anterior lumbar
      interbody fusion (ALIF) from the Spine Tango registry. Two linear multivariate
      regression models were built to assess the associations of patient
      characteristics with back and leg pain relief. The following covariates were
      included in the models: patient age and sex, disc herniation as additional
      diagnosis, number of treated segments, level of treated segment, treatment type
      (VTDR, ALIF), preoperative back and leg pain levels and follow-up interval.
      RESULTS: Both models showed VTDR to be associated with significantly higher back
      (2.76 points; 95% confidence interval (CI) 1.78 - 3.73; p < 0.001) and leg pain
      (2.12 points; 95% CI 1.12 to 3.13; p < 0.001) relief than ALIF. Other influential
      factors for higher back pain relief were female sex compared with male sex (1.03
      additional points; 95% CI 0.27 to 1.78; p = 0.008), monosegmental surgery
      compared with bisegmental surgery (1.02 additional points; 95% CI 0.21 to 1.83; p
      = 0.014), and higher back pain at baseline (0.87 points additional pain relief
      per level of preoperative back pain; 95% CI 0.70 to 1.03; p < 0.001). Other
      influential factors for leg pain relief were monosegmental surgery (0.93
      additional points; 95% CI 0.10 to 1.77; p = 0.029) and higher leg pain at
      baseline (0.83 points additional pain relief per level of preoperative leg pain;
      95% CI 0.70 to 0.96). In both models the L3/4 segment showed 2.36 points (95% CI 
      4.27 to -0.45; p = 0.016) and 3.69 points (95% CI -5.66 to -1.71; p < 0.001) less
      pain relief than L5/S1. DISCUSSION: Significantly higher back and leg pain relief
      were observed after viscoelastic total disc replacement in comparison with
      anterior lumbar interbody fusion. The new less rigid materials used in the second
      generation total disc replacements (TDRs) may make artificial disc replacement an
      increasingly attractive option for patients with degenerative lumbar disc
      disease. Further controlled and long-term follow-up studies are required for more
      detailed comparisons of the outcomes of these types of disc implants. The Freedom
      Lumbar Disc is limited by U.S. federal law to investigational use only.

PMID- 26196034
TI  - Relationship between psoas muscle dimensions and post operative thigh pain. A
      possible preoperative evaluation factor.
AB  - INTRODUCTION: Advanced intraoperative neuromonitoring (IONM) is used to attenuate
      postoperative complications and side effects of extreme lateral interbody fusion
      (XLIF). Specific factors relate to the presence of postoperative injury are not
      well understood. This study aims to identify intraoperative variables with
      correlations to new postoperative anterior thigh/groin sensory changes. METHODS:
      Twenty-nine patients with various degenerative lumbar conditions were treated
      with XLIF at a single institution. Mean age was 59 years, 69% were female, and
      21% had undergone previous lumbar surgery. A total of 47 levels (mean 1.6, range
      1-3) were treated with XLIF. Supplemental pedicle screw and rod fixation was used
      in 24 patients (83%). Dynamically-evoked electromyography was used in all cases.
      Analysis of baseline demographic and treatment variables were performed at a per
      patient basis (n = 29), whereas analysis of intraoperative variables were
      performed at a per levels treated basis (n = 47). RESULTS: Within 24 hours
      postoperative, 10 (34%) patients experienced anterior thigh/groin sensory changes
      (4 reported pain only, 5 reported pain plus other sensory changes, and 1
      paresthesia without pain). Symptom resolution occurred at 1 month postoperative
      for 4 patients, at 3 months postoperative for 2 patients. At 3 months
      postoperative, 6 patients had complete symptom resolution, 3 patients had symptom
      improvements, and 1 patient had no change in perioperative symptoms. Psoas
      dimension in the lateral-latero direction were significantly smaller for patients
      with postoperative sensory changes (p = 0.025), and similarly, patients with
      postoperative sensory changes had a significantly higher ratio of psoas muscle in
      the anterior-posterior to lateral-latero directions (p = 0.026). CONCLUSIONS: In
      addition to IONM, MRI evaluation of psoas shape, position, and dimension may be
      of help in preoperative planning of a safe XLIF access and eventually, predict
      those cases with higher risk of approach-related post-operative events.

PMID- 26196035
TI  - On-chip dilution in nanoliter droplets.
AB  - Droplet microfluidics is enabling reactions at nano- and picoliter scale,
      resulting in faster and cheaper biological and chemical analyses. However,
      varying concentrations of samples on a drop-to-drop basis is still a challenging
      task in droplet microfluidics, primarily limited due to lack of control over
      individual droplets. In this paper, we report an on-chip microfluidic droplet
      dilution strategy using three-valve peristaltic pumps. 

PMID- 26196036
TI  - Highly sensitive ligand-binding assays in pre-clinical and clinical applications:
      immuno-PCR and other emerging techniques.
AB  - Recombinant DNA technology and corresponding innovations in molecular biology,
      chemistry and medicine have led to novel therapeutic biomacromolecules as lead
      candidates in the pharmaceutical drug development pipelines. While monoclonal
      antibodies and other proteins provide therapeutic potential beyond the
      possibilities of small molecule drugs, the concomitant demand for supportive
      bioanalytical sample testing creates multiple novel challenges. For example,
      intact macromolecules can usually not be quantified by mass-spectrometry without
      enzymatic digestion and isotopically labeled internal standards are costly and/or
      difficult to prepare. Classical ELISA-type immunoassays, on the other hand, often
      lack the sensitivity required to obtain pharmacokinetics of low dosed drugs or
      pharmacodynamics of suitable biomarkers. Here we summarize emerging state-of-the
      art ligand-binding assay technologies for pharmaceutical sample testing, which
      reveal enhanced analytical sensitivity over classical ELISA formats. We focus on
      immuno-PCR, which combines antibody specificity with the extremely sensitive
      detection of a tethered DNA marker by quantitative PCR, and alternative nucleic
      acid-based technologies as well as methods based on electrochemiluminescence or
      single-molecule counting. Using case studies, we discuss advantages and drawbacks
      of these methods for preclinical and clinical sample testing. 

PMID- 26196037
TI  - Answer to Letter to the Editor.

PMID- 26196038
TI  - Retraction notice to "Decrease in age-related tau hyperphosphorylation and
      cognitive improvement following vitamin D supplementation are associated with
      modulation of brain energy metabolism and redox state" [Neuroscience 262 (2014)
      143-155].

PMID- 26196039
TI  - Professor Fergus Lowe.

PMID- 26196040
TI  - Pollution-Induced Community Tolerance To Diagnose Hazardous Chemicals in Multiple
      Contaminated Aquatic Systems.
AB  - Aquatic ecosystems are often contaminated with large numbers of chemicals, which
      cannot be sufficiently addressed by chemical target analyses. Effect-directed
      analysis (EDA) enables the identification of toxicants in complex contaminated
      environmental samples. This study suggests pollution-induced community tolerance
      (PICT) as a confirmation tool for EDA to identify contaminants which actually
      impact on local communities. The effects of three phytotoxic compounds local
      periphyton communities, cultivated at a reference (R-site) and a polluted site (P
      site), were assessed to confirm the findings of a former EDA study on sediments.
      The sensitivities of R- and P-communities to prometryn, tributyltin (TBT) and N
      phenyl-2-naphthylamine (PNA) were quantified in short-term toxicity tests and
      exposure concentrations were determined. Prometryn and PNA concentrations were
      significantly higher at the P-site, whereas TBT concentrations were in the same
      range at both sites. Periphyton communities differed in biomass, but algal class
      composition and diatom diversity were similar. Community tolerance of P
      communities was significantly enhanced for prometryn, but not for PNA and TBT,
      confirming site-specific effects on local periphyton for prometryn only. Thus,
      PICT enables in situ effect confirmation of phytotoxic compounds at the community
      level and seems to be suitable to support confirmation and enhance ecological
      realism of EDA.

PMID- 26196042
TI  - Descriptions for Articles Introducing a New Game for Health.

PMID- 26196041
TI  - Edaravone, a potent free radical scavenger, reacts with peroxynitrite to produce
      predominantly 4-NO-edaravone.
AB  - OBJECTIVES: 3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone) is used in clinical
      treatment of acute brain infarction to rescue the penumbra, based on its ability
      to prevent lipid peroxidation by scavenging lipid peroxyl radicals. Here, we show
      that edaravone also reacts with peroxynitrite to yield 4-NO-edaravone as the
      major product and 4-NO2-edaravone as a minor product. RESULTS: We observed little
      formation of 3-methyl-1-phenyl-2-pyrazolin-4,5-dione (4-oxoedaravone) and its
      hydrate, 2-oxo-3-(phenylhydrazono)butanoic acid, which are the major free radical
      induced oxidation products of edaravone, suggesting that free radicals are not
      involved in the reaction with peroxynitrite. The reaction of peroxynitrite with
      edaravone is approximately 30-fold greater than with uric acid, a physiological
      peroxynitrite scavenger (reaction rate k = 1.5 * 10 (4)  M(-1) s(-1) vs. 480 M(
      1) s(-1)). DISCUSSION: These results suggest that edaravone functions
      therapeutically as a scavenger of peroxynitrite as well as lipid peroxyl
      radicals, which is consistent with a report that edaravone treatment reduced
      levels of 3-nitrotyrosine in the cerebrospinal fluid of patients with amyotrophic
      lateral sclerosis.

PMID- 26196044
TI  - Levels in Games for Health.
AB  - There is a time-honored procedure in games for pure entertainment wherein games
      challenge their players by offering successfully higher levels of difficulty. An
      eminent researcher proposed that player engagement and enjoyment require the
      player being constantly challenged, but at a level she or he can handle. A game's
      difficulty levels enable the player to face more difficult challenges as she or
      he builds gameplaying skills. Although levels work in games for entertainment, it
      is not clear how effective or important levels are in games for health, or how
      they are designed. We invited several accomplished games for health designers and
      researchers to discuss levels. 

PMID- 26196045
TI  - Big Games: One Company's Experience with Gamification of Health.

PMID- 26196046
TI  - An Exploratory Study of the Impact of Contextual Cues of Violence in an Active
      Videogame.
AB  - OBJECTIVE: With the expanded genres of active videogames, one inevitably raises
      the question of whether it is worthwhile to use active videogames to promote
      physical activity if games involve violent themes. The purpose of the current
      study was to explore the effects of contextual cues of violence in an active
      videogame on (1) state hostility, (2) perceived arousal, (3) game enjoyment, (4)
      perceived effort in the game, and (5) activity intensity in the game. MATERIALS
      AND METHODS: A one-factor between-subjects experiment with three conditions
      (minimal, moderate, and extreme contextual cues of violence) of playing an in
      house-developed active videogame was conducted. Activity intensity was
      objectively measured using the ActiGraph (Pensacola, FL) model GT3X
      accelerometer. Psychological outcomes were measured using established scales.
      RESULTS: We did not find that the level of contextual cues of violence had any
      effect on the outcome variables, although the moderate level of contextual cues
      of violence resulted in a greater amount of feeling mean (P=0.011) and unsociable
      (P=0.038) among the players immediately after gameplay than players in the
      minimal contextual cues of violence condition. We did not find any statistically
      significant difference among the three conditions in terms of enjoyment,
      perceived arousal, or activity intensity. CONCLUSIONS: This study empirically
      examined the effects of contextual cues of violence in active videogames on
      player hostility, arousal, and enjoyment after gameplay as well as their physical
      activity intensity during gameplay. These findings provide some initial evidence
      to guide active videogame designers and researchers on how to design the games to
      be more engaging and thus elicit more activities among the players.

PMID- 26196047
TI  - Building a Better Mousetrap (Exergame) to Increase Youth Physical Activity.
AB  - Although exergames have been demonstrated to induce moderate levels of physical
      activity (PA) if played as designed, there is conflicting evidence on use of
      exergaming leading to increased habitual PA. Exergames have increased PA in some
      home and school studies, but not others. Exergames have been used in community
      centers to good effect, but this has not generally been validated with research.
      PA from exergames may be enhanced by innovative use of sensors, "fun"-enhancing
      procedures, tailored messaging, message framing, story or narrative, goal
      setting, feedback, and values-based messaging. Research is needed on PA-enhancing
      procedures used within exergames for youth to provide a firmer foundation for the
      design and use of exergames in the future. 

PMID- 26196048
TI  - Gaming Habits and Opinions of Brazilian Medical School Faculty and Students:
      What's Next?
AB  - OBJECTIVE: This study assessed habits and opinions of medical educators and
      students from a Brazilian medical school about electronic games for learning or
      for fun. MATERIALS AND METHODS: A questionnaire was sent to Universidade Estadual
      de Londrina medical school faculty members and undergraduate students. RESULTS:
      From the 50 faculty members, 20 percent reported regular use of electronic games
      (at least once a week), spending 1 hour/week with games (median). Among 302
      medical students, 37 percent reported regular gaming. Students spent 3 hours/week
      playing games (median). Male students played games 4.4 times more often than
      female students. About 90 percent of faculty members and students believed that
      games are useful for medical education, and >80 percent would like to play games
      for education of health professionals, but only one-third of students and one
      fifth of faculty had already played one of such games. More than 80 percent of
      faculty would like to use a game for their educational activities. The main
      obstacles to incorporation of games into medical education, reported by faculty
      members, were associated with lack of knowledge on available options, lack of
      time to develop new activities, and lack of resources or institutional support.
      CONCLUSIONS: Playing electronic games is common among medical faculty and
      students, who both present very positive opinions about games for learning, but
      the scarcity of available options and the lack of institutional support prevent a
      more widespread adoption of medical education games.

PMID- 26196049
TI  - Will Nintendo "Wii Fit" Get You Fit? An Evaluation of the Energy Expenditure from
      Active-Play Videogames.
AB  - OBJECTIVE: This study aimed to determine whether Nintendo((r)) (Redmond, WA) "Wii
      FitTM" games can help individuals meet physical activity recommendations.
      SUBJECTS AND METHODS: Thirty young healthy volunteers were recruited for this
      randomized crossover study to evaluate the energy expenditure associated with (1)
      a 30-minute "Wii Fit Free Run," (2) three 10-minute bouts of "Wii Fit" aerobic
      games ("Rhythm Boxing," "Super Hula Hoop," and "Advanced Steps"), and (3) 30
      minute treadmill running/walking. Energy expenditure was measured by indirect
      calorimetry using breath-by-breath analyses of O2 consumption and CO2 production.
      RESULTS: The "Wii Fit" conditions produced a moderate exercise intensity (5.0,
      4.1, 3.9, and 3.8 metabolic equivalents [METs] in "Free Run," "Rhythm Boxing,"
      "Super Hula Hoop," and "Advanced Steps"), whereas the treadmill running/walking
      produced a vigorous exercise intensity (METs=8.0). Based on federal guidelines,
      an individual could achieve the minimum weekly goal of 500 MET-minutes by playing
      selected "Wii Fit" aerobics games for 20-26 minutes a day, 5 days a week.
      CONCLUSIONS: Although not as vigorous as the treadmill, active-play videogames
      such as "Wii Fit" may provide an alternative way to encourage exercise and
      increase adoption and adherence to the physical activity guidelines.

PMID- 26196050
TI  - Measurement Properties of "Wii Fit Free Jogging" Virtual Distance.
AB  - OBJECTIVE: The aim of this study was to examine the measurement properties of an
      outcome associated with the Nintendo((r)) (Kyoto, Japan) game "WiiTM Fit Free
      Jogging" called virtual distance. Investigations into virtual distance were
      carried out with a view towards using this outcome measure as a tool to estimate
      fitness as part of a self-paced field-based exercise test. MATERIALS AND METHODS:
      Virtual distance achieved was recorded while participants jogged on a treadmill
      and stepped up and down a standardized step and while the game controllers (Wii
      remotes) were attached to electrically powered pedals moving at steady rates.
      Virtual distance was recorded at different time points and different speeds,
      using different consoles, using different Wii remotes, and using different
      virtual characters. RESULTS: When movement of the Wii remote was kept constant,
      there was no significant difference in virtual distance reached at different
      times, with different consoles, with different Wii remotes, or with different
      virtual characters (P<0.05). There was a significant difference between virtual
      distances reached when the speed of movement of the Wii remote was changed. An
      increase in the speed of jogging on the spot, an increase in the rate of stepping
      per minute, and an increase in rotations per minute on automated pedals all
      resulted in increased virtual distance. At a constant speed, the rate of increase
      in virtual distance with time was consistent. CONCLUSIONS: Virtual distance
      appears to be a reliable measure that is sensitive to changes in the speed of
      movement of Wii remotes.

PMID- 26196051
TI  - Cyber Buddy Is Better than No Buddy: A Test of the Kohler Motivation Effect in
      Exergames.
AB  - OBJECTIVE: Although exergames are popular, few people take advantage of the
      potential of group dynamics to motivate play (and achieve associated health
      benefits). One motivation gain phenomenon has shown promise for motivating
      greater effort in partnered exergames: The Kohler effect (working at a task with
      a more capable partner where one's performance is indispensable to the group).
      This article examines whether a Kohler effect can be demonstrated in an exergame
      by exercising with a moderately superior humanoid, software-generated partner.
      MATERIALS AND METHODS: Male and female (n=120; mean age, 19.41 years) college
      students completed a series of plank exercises using "CyBuddy Exercise," a
      program developed specifically for this study. In a lab in an academic building,
      participants completed the exercises individually and, after a rest, were
      randomly assigned to complete the same exercises again, but with a "live" human
      partner (HP) presented virtually, a nearly-human-like, humanoid partner (NHP), a
      hardly human-like, software-generated partner (HHP), or a no-partner control
      condition (IC), with equal numbers in each group (i.e., n=30). Exercise
      persistence, perceived exertion, self-efficacy beliefs, enjoyment, and intentions
      to exercise were recorded and analyzed. RESULTS: A 4*2 analysis of variance on
      the (Block 2 - Block 1) difference scores showed that a significant Kohler
      motivation gain was observed in all partner conditions (compared with IC), but
      persistence was significantly greater with HPs than with either NHP or HHP
      humanoid partners (P<0.05). By the conclusion of the study, there were no
      significant differences among the partnered conditions in perceived exertion,
      self-efficacy, enjoyment, or future intentions to exercise. CONCLUSIONS: These
      results suggest that a software-generated partner can elicit the Kohler
      motivation gain in exergames, but not as strongly as a partner who is thought to
      be human.

PMID- 26196052
TI  - Gameplay and Educational Outcomes: Reminders for Educational Game Development.

PMID- 26196053
TI  - Association between genetic polymorphisms in folate-related enzyme genes and
      infertile men with non-obstructive azoospermia.
AB  - Polymorphisms in the genes encoding enzymes in the folate metabolism pathway have
      been associated with male infertility and chromosome abnormalities. The aim of
      this study was to analyze the distribution of the methylenetetrahydrofolate
      reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase
      (MTRR) polymorphisms in fertile men and infertile men with non-obstructive
      azoospermia (NOA). A case-control study comprising 85 infertile men with NOA and
      246 fertile men as controls was carried out. MTHFR c.677C > T (rs1801133), MTHFR
      c.1298A > C (rs1801131), MTR c.2756A > G (rs1805087), and MTRR c.66A > G
      (rs1801394) polymorphisms were determined using the polymerase chain reaction
      restriction fragment length polymorphism technique. There were significant
      differences in AC + CC genotype (OR = 1.9, 95% CI = 1.1-3.2) and C allele
      frequencies (OR = 1.8, 95% CI = 1.2-2.8) of MTHFR c.1298A > C polymorphism
      between NOA patients and controls after applying the Bonferroni correction.
      Moreover, the 1298AC genotype, 1298AC + CC genotype, and 1298C allele frequencies
      were statistically significant in NOA with chromosomal abnormalities and/or a Y
      chromosome deletion compared to the controls (AC genotype: OR = 3.0; AC + CC
      genotype: OR = 3.0; C allele: OR = 2.3). Considering the other polymorphisms, no
      differences were found between cases and controls. Our findings suggest the MTHFR
      c.1298A > C polymorphism is associated with an increased risk of male
      infertility, i.e., NOA.

PMID- 26196054
TI  - Should antidepressant medication be used in the elderly?
AB  - Late-life depression is a serious illness accompanied by medical morbidity,
      cognitive decline and risk of suicide. Antidepressant medications are a
      cornerstone of treatment for depressed elders. Although they are optimally
      provided in conjunction with psychotherapy, in many cases they are used alone.
      Recently, concern has developed over modern antidepressant medication, including
      concerns about their ultimate efficacy and particular risks that may be seen in
      older adult populations. Ultimately, antidepressant medications are effective for
      many individuals and continue to play an important role in treating depressed
      elders, although the potential risks must be weighed with the patient and their
      families. Current data do not support restriction of their use and untreated
      depression has serious negative health consequences. Patients need treatments
      with better efficacy and safety, including new pharmacological options and better
      access to and dissemination of nonpharmacological treatment. 

PMID- 26196055
TI  - Evaluation of a multi-epitope subunit vaccine against avian leukosis virus
      subgroup J in chickens.
AB  - The intricate sequence and antigenic variability of avian leukosis virus subgroup
      J (ALV-J) have led to unprecedented difficulties in the development of vaccines.
      Much experimental evidence demonstrates that ALV-J mutants have caused immune
      evasion and pose a challenge for traditional efforts to develop effective
      vaccines. To investigate the potential of a multi-epitope vaccination strategy to
      prevent chickens against ALV-J infections, a recombinant chimeric multi-epitope
      protein X (rCMEPX) containing both immunodominant B and T epitope concentrated
      domains selected from the major structural protein of ALV-J using bioinformatics
      approach was expressed in Escherichia coli Rosetta (DE3). Its immunogenicity and
      protective efficacy was studied in chickens. The results showed that rCMEPX could
      elicit neutralizing antibodies and cellular responses, and antibodies induced by
      rCMEPX could specifically recognize host cell naturally expressed ALV-J proteins,
      which indicated that the rCMEPX is a good immunogen. Challenge experiments showed
      80% chickens that received rCMEPX were well protected against ALV-J challenge.
      This is the first report of a chimeric multi-epitope protein as a potential
      immunogen against ALV-J. 

PMID- 26196056
TI  - Isolation and characterization of a Korean porcine epidemic diarrhea virus strain
      KNU-141112.
AB  - Severe outbreaks of porcine epidemic diarrhea virus (PEDV) have re-emerged in
      Korea and rapidly swept across the country, causing tremendous economic losses to
      producers and customers. Despite the availability of PEDV vaccines in the
      domestic market, the disease continues to plague the Korean pork industry,
      raising issues regarding their protective efficacy and new vaccine development.
      Therefore, PEDV isolation in cell culture is urgently needed to develop
      efficacious vaccines and diagnostic assays and to conduct further studies on the
      virus biology. In the present study, one Korean PEDV strain, KOR/KNU-141112/2014,
      was successfully isolated and serially propagated in Vero cells for over 30
      passages. The in vitro and in vivo characteristics of the Korean PEDV isolate
      were investigated. Virus production in cell culture was confirmed by
      cytopathology, immunofluorescence, and real-time RT-PCR. The infectious virus
      titers of the viruses during the first 30 passages ranged from 10(5.1) to 10(8.2)
      TCID50 per ml. The inactivated KNU-141112 virus was found to mediate potent
      neutralizing antibody responses in immunized guinea pigs. Animal studies showed
      that KNU-141112 virus causes severe diarrhea and vomiting, fecal shedding, and
      acute atrophic enteritis, indicating that strain KNU-141112 is highly
      enteropathogenic in the natural host. In addition, the entire genomes or complete
      S genes of KNU-141112 viruses at selected cell culture passages were sequenced to
      assess the genetic stability and relatedness. Our genomic analyses indicated that
      the Korean isolate KNU-141112 is genetically stable during the first 30 passages
      in cell culture and is grouped within subgroup G2b together with the recent re
      emergent Korean strains. 

PMID- 26196057
TI  - Noncationic Rigid and Anisotropic Coiled-Coil Proteins Exhibit Cell-Penetration
      Activity.
AB  - Numerous cationic peptides that penetrate cells have been studied intensively as
      drug delivery system carriers for cellular delivery. However, cationic molecules
      tend to be cytotoxic and cause inflammation, and their stability in the blood is
      usually low. We have previously demonstrated that a rigid and fibrous cationic
      coiled-coil protein exhibited cell-penetrating ability superior to that of
      previously reported cell-penetrating peptides. Making use of structural
      properties, here we describe the cell-penetrating activity of a rigid and fibrous
      coiled-coil protein with a noncationic surface. A fibrous coiled-coil protein of
      pI 6.5 penetrated 100% of the cells tested in vitro at a concentration of 500 nM,
      which is comparable to that of previously reported cell-penetrating peptides. We
      also investigated the effect of cell-strain dependency and short-term
      cytotoxicity. 

PMID- 26196058
TI  - Zeolitic Imidazole Framework (ZIF) Nanospheres for Easy Encapsulation and
      Controlled Release of an Anticancer Drug Doxorubicin under Different External
      Stimuli: A Way toward Smart Drug Delivery System.
AB  - The conventional drug delivery systems made from organic- or inorganic-based
      materials suffer from some problems associated with uncontrolled drug release,
      biocompatibility, cytotoxicity, and so forth. To overcome these problems,
      zeolitic imidazole framework (ZIF) hybrid materials can be one of the solutions.
      Here, we report a very easy and successful encapsulation of an anticancer drug
      doxorubicin inside two ZIFs, namely, ZIF-7 and ZIF-8, which are little explored
      as drug delivery systems, and we studied the controlled release of the drug from
      these two ZIFs under external stimuli such as change in pH and upon contact with
      biomimetic systems. Experimental results demonstrate that ZIF-7 remains intact
      when the pH changes from physiological condition to acidic condition, whereas ZIF
      8 successfully releases drug under acidic condition. Interestingly, both the ZIFs
      are excellent for drug release when they come in contact with micelles or
      liposomes. In the case of ZIF-8, the drug delivery can be controlled for 3 h,
      whereas its analogue ZIF-7 delivers the drug for a time span of 10 h. We
      explained the reluctance of ZIF-7 toward drug release in terms of rigidity. This
      study highlights that by using different ZIFs and liposomes, the drug release
      rate can be easily modulated, which implies ample possibility for ZIFs as a good
      drug delivery system. The study shows a novel strategy for easy drug
      encapsulation and its release in a controlled manner, which will help future
      development of the drug delivery system. 

PMID- 26196059
TI  - Facile Synthesis of Na0.33V2O5 Nanosheet-Graphene Hybrids as Ultrahigh
      Performance Cathode Materials for Lithium Ion Batteries.
AB  - Na0.33V2O5 nanosheet-graphene hybrids were successfully fabricated for the first
      time via a two-step route involving a novel hydrothermal method and a freeze
      drying technique. Uniform Na0.33V2O5 nanosheets with a thickness of about 30 nm
      are well-dispersed between graphene layers. The special sandwich-like
      nanostructures endow the hybrids with high discharge capacity, good cycling
      stability, and superior rate performance as cathodes for lithium storage.
      Desirable discharge capacities of 313, 232, 159, and 108 mA.h.g(-1) can be
      delivered at 0.3, 3, 6, and 9 A.g(-1), respectively. Moreover, the Na0.33V2O5
      graphene hybrids can maintain a high discharge capacity of 199 mA.h.g(-1) after
      400 cycles even at an extremely high current density of 4.5 A.g(-1), with an
      average fading rate of 0.03% per cycle. 

PMID- 26196060
TI  - Enzyme Induced Stiffening of Nanoparticle-Hydrogel Composites with Structural
      Color.
AB  - The passive monitoring of biological environments by soft materials has a variety
      of nanobiotechnology applications; however, invoking distinct transitions in
      geometric, mechanical or optical properties remains a prevalent design challenge.
      We demonstrate here that close-packed nanoparticle-hydrogel composites can
      progress through a substantial shift in such properties by the use of a chemical
      to-physical cross-link transition mediated by the catalytic activity of different
      proteases. Catalytic cleavage of the original hydrogel network structure
      initiates the self-assembled formation of a secondary, physically cross-linked
      network, causing a 1200% increase in storage modulus. Furthermore, this unique
      mechanism can be fabricated as a 3D photonic crystal with broad (~240 nm),
      visible responses to the targeted enzymes. Moreover, the material provided
      threshold responses, requiring a certain extent of proteolytic activity before
      the transition occurred. This allowed for the fabrication of Boolean logic gates
      (OR and AND), which responded to a specific assortment of proteases. Ultimately,
      this mechanism enables the design of stimuli-responsive hydrogels, which can
      proceed through a secondary network formation, after an energetic barrier has
      been breached. Protease responsive hydrogel nanocomposites, described here, could
      offer avenues in degradation-stiffening and collapsing materials for a variety of
      biomaterial applications. 

PMID- 26196061
TI  - A Selective, Cell-Permeable Nonphosphorylated Bicyclic Peptidyl Inhibitor against
      Peptidyl-Prolyl Isomerase Pin1.
AB  - Pin1 regulates the levels and functions of phosphoproteins by catalyzing
      phosphorylation-dependent cis/trans isomerization of peptidyl-prolyl bonds.
      Previous Pin1 inhibitors contained phosphoamino acids, which are metabolically
      unstable and have poor membrane permeability. In this work, we report a cell
      permeable and metabolically stable nonphosphorylated bicyclic peptide as a potent
      and selective Pin1 inhibitor, which inhibited the intracellular Pin1 activity in
      cultured mammalian cells but had little effect on other isomerases such as Pin4,
      FKBP12, or cyclophilin A. 

PMID- 26196062
TI  - Gene structure variation in segmental duplication block C of human chromosome 7q
      11.23 during primate evolution.
AB  - Segmental duplication, or low-copy repeat (LCR) event, occurs during primate
      evolution and is an important source of genomic diversity, including gain or loss
      of gene function. The human chromosome 7q 11.23 is related to the William-Beuren
      syndrome and contains large region-specific LCRs composed of blocks A, B, and C
      that have different copy numbers in humans and different primates. We analyzed
      the structure of POM121, NSUN5, FKBP6, and TRIM50 genes in the LCRs of block C.
      Based on computational analysis, POM121B created by a segmental duplication
      acquired a new exonic region, whereas NSUN5B (NSUN5C) showed structural variation
      by integration of HERV-K LTR after duplication from the original NSUN5 gene. The
      TRIM50 gene originally consists of seven exons, whereas the duplicated TRIM73 and
      TRIM74 genes present five exons because of homologous recombination-mediated
      deletion. In addition, independent duplication events of the FKBP6 gene generated
      two pseudogenes at different genomic locations. In summary, these clustered genes
      are created by segmental duplication, indicating that they show dynamic
      evolutionary events, leading to structure variation in the primate genome. 

PMID- 26196063
TI  - Novel BCOR mutation in a boy with Lenz microphthalmia/oculo-facio-cardio-dental
      (OFCD) syndrome.
AB  - Lenz microphthalmia syndrome and oculo-facio-cardio-dental syndrome (OFCD) are
      allelic X-linked syndromes and similarly characterized by ocular, distinctive
      facial morphology, cardiac, dental malformations and intellectual disability. We
      report a seven-month-old boy with congenital glaucoma, complex cardiac defect,
      dextrocardia and cerebral white matter hypoplasia suggestive of Lenz
      microphthalmia/OFCD syndrome. Molecular testing revealed a novel missense
      mutation (c.G1619A; p.R540Q) in BCOR. This boy might be the third male patient
      with a BCOR mutation based on literature search. Previously, Xenopus studies
      showed that BCOR is required for vertebrate laterality determination. Our finding
      provides additional support that the manifestations of defective lateral
      patterning and dextrocardia are associated with Lenz microphthalamia/OFCD
      syndrome. 

PMID- 26196064
TI  - Synthesis, Solid-State Structures, and Molecular Recognition of Chiral Molecular
      Tweezer and Related Structures Based on a Rigid Bis-Naphthalene Cleft.
AB  - The rigid and nonchiral bis-naphthalene cleft was used for the first time as a
      scaffold to build a chiral molecular tweezer. The molecular tweezer and its
      related compounds have been synthesized and carefully characterized by X-ray
      crystallography and NMR spectroscopy. Their solid-state structures and molecular
      recognition properties have also been studied. 

PMID- 26196065
TI  - An Experimental and Computational Study of the Gas-Phase Acidities of the Common
      Amino Acid Amides.
AB  - Using proton-transfer reactions in a Fourier transform ion cyclotron resonance
      mass spectrometer and correlated molecular orbital theory at the G3(MP2) level,
      gas-phase acidities (GAs) and the associated structures for amides corresponding
      to the common amino acids have been determined for the first time. These values
      are important because amino acid amides are models for residues in peptides and
      proteins. For compounds whose most acidic site is the C-terminal amide nitrogen,
      two ions populations were observed experimentally with GAs that differ by 4-7
      kcal/mol. The lower energy, more acidic structure accounts for the majority of
      the ions formed by electrospray ionization. G3(MP2) calculations predict that the
      lowest energy anionic conformer has a cis-like orientation of the [-C(?O)NH](-)
      group whereas the higher energy, less acidic conformer has a trans-like
      orientation of this group. These two distinct conformers were predicted for
      compounds with aliphatic, amide, basic, hydroxyl, and thioether side chains. For
      the most acidic amino acid amides (tyrosine, cysteine, tryptophan, histidine,
      aspartic acid, and glutamic acid amides) only one conformer was observed
      experimentally, and its experimental GA correlates with the theoretical GA
      related to side chain deprotonation. 

PMID- 26196066
TI  - Aerobic capacity is associated with global functioning in people with
      schizophrenia.
AB  - BACKGROUND: Although antipsychotic medications help manage clinical symptom
      severity, most people with schizophrenia continue to function poorly in the
      community. OBJECTIVE: To determine whether the Global Assessment of Functioning
      (GAF) score is associated with aerobic capacity in people with schizophrenia.
      METHOD: Thirty-four male (34.1 +/- 12.0 years) and 16 female (33.1 +/- 8.7 years)
      persons with schizophrenia performed the Astrand-Rhyming cycle ergometer test in
      order to estimate the maximal oxygen uptake (VO2max) and were assessed with the
      GAF, the Psychosis Evaluation tool for Common use by Caregivers and the
      International Physical Activity Questionnaire. RESULTS: The mean GAF-score was
      41.9 +/- 9.4, while the mean estimated VO2max was 34.5 +/- 8.7mlO2/min/kg. There
      was a moderate association between the GAF-score and VO2max (r = 0.45, p <
      0.001). Positive, negative and cognitive symptoms were negatively (p < 0.05)
      associated with the GAF-score, physical activity participation positively (p <
      0.05). A backward regression analysis demonstrated that VO2max explained 19.1% of
      the GAF-score variance. CONCLUSION: In people with schizophrenia, the aerobic
      capacity is associated with a person's global functioning. Clinicians should
      consider incorporating assessment of aerobic capacity into their test battery in
      order to measure the health consequences of schizophrenia and its treatment.

PMID- 26196067
TI  - Long-term frequent prescribed fire decreases surface soil carbon and nitrogen
      pools in a wet sclerophyll forest of Southeast Queensland, Australia.
AB  - Prescribed fire is one of the most widely-used management tools for reducing fuel
      loads in managed forests. However the long-term effects of repeated prescribed
      fires on soil carbon (C) and nitrogen (N) pools are poorly understood. This study
      aimed to investigate how different fire frequency regimes influence C and N pools
      in the surface soils (0-10 cm). A prescribed fire field experiment in a wet
      sclerophyll forest established in 1972 in southeast Queensland was used in this
      study. The fire frequency regimes included long unburnt (NB), burnt every 2 years
      (2yrB) and burnt every 4 years (4yrB), with four replications. Compared with the
      NB treatment, the 2yrB treatment lowered soil total C by 44%, total N by 54%, HCl
      hydrolysable C and N by 48% and 59%, KMnO4 oxidizable C by 81%, microbial biomass
      C and N by 42% and 33%, cumulative CO2-C by 28%, NaOCl-non-oxidizable C and N by
      41% and 51%, and charcoal-C by 17%, respectively. The 4yrB and NB treatments
      showed no significant differences for these soil C and N pools. All soil labile,
      biologically active and recalcitrant and total C and N pools were correlated
      positively with each other and with soil moisture content, but negatively
      correlated with soil pH. The C:N ratios of different C and N pools were greater
      in the burned treatments than in the NB treatments. This study has highlighted
      that the prescribed burning at four year interval is a more sustainable
      management practice for this subtropical forest ecosystem.

PMID- 26196068
TI  - Assessing the impacts of sustainable agricultural practices for water quality
      improvements in the Vouga catchment (Portugal) using the SWAT model.
AB  - The extensive use of fertilizers has become one of the most challenging
      environmental issues in agricultural catchment areas. In order to reduce the
      negative impacts from agricultural activities and to accomplish the objectives of
      the European Water Framework Directive we must consider the implementation of
      sustainable agricultural practices. In this study, we assess sustainable
      agricultural practices based on reductions in N-fertilizer application rates
      (from 100% to 0%) and N-application methods (single, split and slow-release)
      across key agricultural land use classes in the Vouga catchment, Portugal. The
      SWAT model was used to relate sustainable agricultural practices, agricultural
      yields and N-NO3 water pollution deliveries. Results show that crop yields as
      well as N-NO3 exportation rates decrease with reductions in N-application rates
      and single N-application methods lead to lower crop yields and higher N-NO3
      exportation rates as compared to split and slow-release N-application methods. 

PMID- 26196069
TI  - Responses of absolute and specific soil enzyme activities to long term additions
      of organic and mineral fertilizer.
AB  - Long-term phosphorus (P) and nitrogen (N) applications may seriously affect soil
      microbial activity. A long-term field fertilizer application trial was
      established on reddish paddy soils in the subtropical region of southern China in
      1998. We assessed the effects of swine manure and seven different rates or ratios
      of NPK fertilizer treatments on (1) the absolute and specific enzyme activities
      per unit of soil organic carbon (SOC) or microbial biomass carbon (MBC) involved
      in C, N, and P transformations and (2) their relationships with soil
      environmental factors and soil microbial community structures. The results showed
      that manure applications led to increases in the absolute and specific activities
      of soil beta-1,4-glucosidase(betaG), beta-1,4-N-acetylglucosaminidase (NAG), and
      leucine aminopeptidase (LAP). The absolute and specific acid phosphatase (AP)
      activities decreased as mineral P fertilizer application rates and ratios
      increased. Redundancy analysis (RDA) showed that there were negative correlations
      between absolute and specific AP activities, pH, and total P contents, while
      there were positive correlations between soil absolute and specific betaG, NAG,
      and LAP enzyme activities, and SOC and total N contents. RDA showed that the
      contents of actinomycete and Gram-positive bacterium PLFA biomarkers are more
      closely related to the absolute and specific enzyme activities than the other
      PLFA biomarkers (P<0.01). Our results suggest that both the absolute and specific
      enzyme activities could be used as sensitive soil quality indicators that provide
      useful linkages with the microbial community structures and environmental
      factors. To maintain microbial activity and to minimize environmental impacts, P
      should be applied as a combination of inorganic and organic forms, and total P
      fertilizer application rates to subtropical paddy soils should not exceed 44 kg P
      ha(-1) year(-1).

PMID- 26196070
TI  - Re-evaluation of groundwater monitoring data for glyphosate and bentazone by
      taking detection limits into account.
AB  - Current regulatory assessment of pesticide contamination of Danish groundwater is
      exclusively based on samples with pesticide concentrations above detection limit.
      Here we demonstrate that a realistic quantification of pesticide contamination
      requires the inclusion of "non-detect" samples i.e. samples with concentrations
      below the detection limit, as left-censored observations. The median calculated
      pesticide concentrations are shown to be reduced 10(4) to 10(5) fold for two
      representative herbicides (glyphosate and bentazone) relative to the median
      concentrations based upon observations above detection limits alone. 

PMID- 26196071
TI  - Apportioned contributions of PM2.5 fine aerosol particles over the Maldives
      (northern Indian Ocean) from local sources vs long-range transport.
AB  - Urban-like plumes of gases and particulate matter originating from the South
      Asian region are frequently observed over the Indian Ocean, especially during the
      dry winter period. However, in addition to the strong sources on mainland South
      Asia, there are also local Maldivian emissions. The local contributions to the
      load of fine particulate matter (PM2.5) in the Maldivian capital Male was
      assessed using the well-established Maldives Climate Observatory at Hanimaadhoo
      (MCOH) to represent local background, recording the long-range transported
      component for a full-year synoptic campaign at both sites in 2013. The year-round
      levels in both Male and MCOH are strongly influenced by the seasonality of the
      monsoon cycle, including precipitation patterns and air-mass transport pathways,
      with lower levels during the wet summer season. The annual-average PM2.5 levels
      in Male are higher (avg. 19 MUg/m3) than at MCOH (avg. 13 MUg/m3) with the
      difference being the largest during the summer, when local emissions play a
      larger role. The 24-h World Health Organization (WHO) PM2.5 health guideline was
      surpassed for the weeklong collections in 71% of the cases in Male and in 74% of
      the cases for Hanimaadhoo. This study shows that in the dry/winter season 90+/
      11% of PM2.5 levels in Male could be from long-range transport with only 8+/-11%
      from local emissions while in the wet/monsoon season the relative contributions
      are about equal. The concentrations of organic carbon (OC) and elemental carbon
      (EC) showed similar seasonal patterns as bulk mass PM2.5. The relative
      contribution of total carbonaceous matter to bulk mass PM2.5 was 17% in Male and
      13% at MCOH, suggesting larger contributions from incomplete combustion practices
      in the Male local region.

PMID- 26196072
TI  - A simulation-based suitability index of the quality and quantity of agricultural
      drainage water for reuse in irrigation.
AB  - The suitability of agricultural drainage water (ADW) for reuse in irrigation was
      indexed based on a simulation of quality and quantity. The ADW reuse index (DWRI)
      has two components; the first one indicates the suitability of water quality
      (QLT) for reuse in irrigation based on the mixing ratio of ADW to canal
      irrigation water without violating the standards of using mixed water in
      irrigation, while the second indicates the available water quantity (QNT) based
      on the ratio of the available ADW to the required reuse discharge to meet the
      irrigation requirements alongside the drain. The QLT and QNT values ranged from 0
      to >=3 and from 0 to >=0.40, respectively. Correspondingly, five classes from
      excellent to poor and from high scarcity to no scarcity were proposed to classify
      the QLT and QNT values, respectively. This approach was then applied to the
      Gharbia drain in the Nile Delta, Egypt, combined with QUAL2Kw simulations in the
      summer and winter of 2012. The QLT values along the drain ranged from 1.11 to
      2.91 and 0.68 to 1.73 for summer and winter, respectively. Correspondingly, the
      QLT classes ranged from good to very good and from fair to good, respectively. In
      regard to QNT, values ranged from 0.10 to 0.62 and from 0.10 to 0.88 for summer
      and winter, respectively. Correspondingly, the QNT classes ranged from medium
      scarcity to no scarcity for both seasons. The demonstration of DWRI in the
      Gharbia drain suggests that the proposed index presents a simple tool for
      spatially evaluating the suitability of ADW for reuse in irrigation. 

PMID- 26196073
TI  - Alcohol and cocaine co-consumption in two European cities assessed by wastewater
      analysis.
AB  - The quantitative determination of urinary biomarkers in raw wastewater has
      emerged in recent years as a promising tool for estimating the consumption of
      illicit drugs, tobacco and alcohol in a population and for comparing local and
      temporal trends. In this study, a three-year monitoring campaign (2012-2014) was
      conducted to compare alcohol and cocaine use in two European cities (Santiago de
      Compostela, Spain, and Milan, Italy) by wastewater analysis. Ethyl sulphate and
      benzoylecgonine were used, respectively, as biomarkers of ethanol and cocaine
      consumption and cocaethylene as an indicator of co-consumption of both
      substances. Biomarkers were measured using liquid chromatography-tandem mass
      spectrometry and concentrations were converted to rates of consumption using
      specific correction factors. Results were statistically compared in terms of
      geographic and temporal tendencies. Alcohol intake was significantly higher in
      Santiago than in Milan (13.6L versus 5.1L ethanol/1000 people day, averages).
      Cocaine use was higher in Milan than in Santiago de Compostela (800 versus 632
      mg/1000 people day, averages). A significant higher consumption of both alcohol
      and cocaine was observed during the weekends (~23-75% more than on weekdays) in
      both cities. In terms of years, slight changes were observed, but no clear trends
      as representative of the whole year could be identified because of the limited
      number of days sampled. Co-consumption was evaluated using the
      cocaethylene/benzoylecgonine ratio, which was higher during the weekend in both
      cities (58% in Santiago and 47% in Milan over the non-weekend day means),
      indicating a greater co-consumption when cocaine is used as a recreational drug.
      Wastewater-based epidemiology gave estimates of alcohol and cocaine use in
      agreement with previous wastewater studies and with recent European surveillance
      and prevalence data, and weekly profiles of use and preferential patterns of
      consumption could be plot.

PMID- 26196074
TI  - Occurrence, source analysis and risk assessment of androgens, glucocorticoids and
      progestagens in the Hailing Bay region, South China Sea.
AB  - The occurrence and spatial distribution of 40 steroids in the environmental
      matrices of the Hailing Bay region, South China Sea, were investigated by rapid
      resolution liquid chromatography-tandem mass spectrometry (RRLC-MS/MS).
      Seventeen, 14 and 11 of 40 steroids were detected with the concentrations ranging
      from 0.04 (testosterone) to 40.00 ng/L (prednisolone), 1.33 (4-hydroxy-androst-4
      ene-17-dione) to 1855 ng/L (androsta-1,4-diene-3,17-dione) and <0.19 (androsta
      1,4-diene-3,17-dione) to 2.37 ng/g (progesterone) in the seawater, the municipal
      sewage discharged effluent and the sediment samples, respectively. The
      concentrations and risk quotients (RQs) of the steroids detected in the water
      samples decreased in the order of municipal sewage discharge
      site>wharves~aquaculture zones~tourism areas>offshore areas. The distribution of
      steroids in the marine environment was significantly correlated with the levels
      of chemical oxygen demand (COD) and ammonium nitrogen (NH4-N). Source analysis
      indicated that untreated municipal sewage was the main source of steroids in the
      marine environment. Furthermore, progesterone was found to be a reliable chemical
      indicator to surrogate different steroids in both the water and sediment phases
      based on the correlation analysis.

PMID- 26196075
TI  - Detection and Full-Length Genome Characterization of Novel Canine Vesiviruses.
AB  - Vesiviruses have been detected in several animal species and as accidental
      contaminants of cells. We detected vesiviruses in asymptomatic kennel dogs
      (64.8%) and symptomatic (1.1%) and asymptomatic (3.5%) household dogs in Italy.
      The full-length genome of 1 strain, Bari/212/07/ITA, shared 89%-90% nt identity
      with vesiviruses previously detected in contaminated cells. 

PMID- 26196076
TI  - (-)Epigallocatechin-3-gallate prevents the reserpine-induced impairment of short
      term social memory in rats.
AB  - Reserpine has been confirmed to induce cognitive dysfunction and increase brain
      neural oxidative stress. Green tea catechins, particularly (-)epigallocatechin-3
      gallate (EGCG), have strong antioxidative properties and can protect against
      numerous oxidative damages. In this study, we examined the possible protective
      effects of EGCG on reserpine-induced impairment of short-term memory in rats.
      Reserpine (1 mg/kg, intraperitoneal)-induced memory impairment was assessed using
      the social recognition task method; locomotor activity and the olfactory
      discrimination ability were not altered as measured by an open-field test and an
      olfactory discrimination test, respectively. EGCG treatment (100 and 300 mg/kg,
      intraperitoneal, for 7 days, starting 6 days before the reserpine injection)
      could improve the worsened social memory of reserpine-treated rats. Also, EGCG
      treatment reduced reserpine-induced lipid peroxidation and enhanced the
      antioxidation power in the hippocampi of reserpine-treated rats. These results
      suggest a protective effect of EGCG in treating reserpine-induced impairment of
      memory, most probably through its powerful antioxidative activities. Accordingly,
      EGCG may hold a clinically relevant value in preventing reserpine-induced
      cognitive dysfunction.

PMID- 26196077
TI  - Elemental Mercury in Natural Waters: Occurrence and Determination of Particulate
      Hg(0).
AB  - Elemental mercury, Hg(0), is ubiquitous in water and involved in key Hg
      biogeochemical processes. It is extensively studied as a purgeable dissolved
      species, termed dissolved gaseous mercury (DGM). Little information is available
      regarding nonpurgeable particulate Hg(0) in water, Hg(0) bound to suspended
      particulate matter (SPM), which is presumably present due to high affinity of
      Hg(0) adsorption on solids. By employing stable isotope tracer and isotope
      dilution (ID) techniques, we investigated the occurrence and quantification of
      particulate Hg(0) after Hg(0) being spiked into natural waters, aiming to provide
      firsthand information on particulate Hg(0) in water. A considerable fraction of
      (201)Hg(0) spiked in water (about 70% after 4 h equilibration) was bound to SPM
      and nonpurgeable, suggesting the occurrence of particulate Hg(0) in natural
      waters. A scheme, involving isotope dilution, purge and trap, and inductively
      coupled plasma mass spectrometry detection, was proposed to quantify particulate
      Hg(0) by the difference between DGM and total Hg(0), determined immediately and
      at equilibration after spiking ID Hg isotope, respectively. The application of
      this newly established method revealed the presence of particulate Hg(0) in
      Florida Everglades water, as the determined DGM levels (0.14 to 0.22 ng L(-1))
      were remarkably lower than total Hg(0) (0.41 to 0.75 ng L(-1)).

PMID- 26196078
TI  - Comparing human and automated support for depression: Fractional factorial
      randomized controlled trial.
AB  - Web-based interventions for people with depressive symptoms are needed and show
      promising effects. However, it is a consistent finding that human support is
      needed and this makes implementation costly. This study investigates the
      adherence and effectiveness of a human-supported and automated-supported web
      based intervention for people with mild to moderate depressive symptomatology,
      and studies the impact of four persuasive technology components. People with mild
      to moderate depressive symptoms according to the Center of Epidemiological
      Studies depression scale self-report questionnaire were included, but no
      diagnosis was made for the study. Participants (n = 239) were randomized into one
      of eight intervention arms, where each level of each component is present in half
      of the intervention arms. On clinical outcomes, there was a significant
      interaction effect between support condition and time, but there was no
      difference on the extent of improvement from baseline to follow-up, only a
      difference in the time-path of improvement. Effect sizes from baseline to follow
      up were 0.89 for automated and 1.00 for human support. There was no significant
      difference on adherence between support condition. We conclude that an automated
      supported web-based intervention for treatment of depression with persuasive
      technology may achieve similar adherence and effectiveness as the same
      intervention with human support. 

PMID- 26196079
TI  - Cellular and molecular mechanisms of the restoration of human APP transgenic
      mouse cognitive dysfunction after transplant of human iPS cell-derived neural
      cells.
AB  - Cholinergic neuronal loss is a common finding in patients with Alzheimer's
      disease (AD) and AD model mice. We previously transplanted neurons derived from
      human induced pluripotent stem (iPS) cells into the hippocampus of human amyloid
      precursor protein transgenic AD model mice. In the present study, we examined the
      cellular and molecular mechanisms involved in the alleviation of cognitive
      dysfunction in transplanted mice. After transplant, mice showed improvement in
      cognitive function, confirming our previous findings. Human choline
      acetyltransferase (ChAT)-positive cholinergic neurons were distributed throughout
      the cortex of the grafted mice. Human and mouse ChAT-positive neurons and alpha7
      nicotinic acetylcholine receptor (alpha7nAChR)-positive neurons were
      significantly increased in the cortex and hippocampus of the grafted mice
      compared with the vehicle-injected mice. In addition, human and mouse vesicular
      GABA transporter (VGAT)-positive neurons were located mainly in the hippocampus
      and, though the number was small, human VGAT-positive neurons were observed in
      the cortex. In the grafted mouse cortex, the number of GABA receptor (GABAR)
      positive neurons of both human origin and mouse origin were significantly
      increased compared with those in the vehicle-injected mouse cortex. The
      alpha7nAChR-positive and GABAR-positive neurons expressed phosphorylated Akt and
      c-fos in the cortex, suggesting that these receptor-expressing neurons were
      possibly activated by the neurotransmitters secreted from the grafted neurons.
      Collectively, the grafted and host neurons may form positive feedback loops via
      neurotransmitter secretion in both the cerebral cortex and hippocampus, leading
      to alleviation of cognitive dysfunction in dementia model mice. 

PMID- 26196080
TI  - An integrated approach for probing the structure and mechanical properties of
      diatoms: Toward engineered nanotemplates.
AB  - The wide variety of diatom frustule shapes and intricate architectures provide
      viable prototypes to guide the design and fabrication of nanodevices and
      nanostructured materials for applications ranging from sensors to nanotemplates.
      In this study, a combined experimental-simulation method was developed to probe
      the porous structure and mechanical behavior of two distinct marine diatom
      species, Coscinodiscus sp. (centric) and Synedra sp. (pennate), through ambient
      nanoindentation and finite element method analysis. These diatom frustule
      dimensions differed largely depending on diatom species with pore diameters d
      ranging from 0.3 to 3.0 MUm. Young's modulus E and hardness H measurements of the
      diatom frustules were obtained via nanoindentation experiments. These values
      varied depending on diatom species (E between 1.1-10.6 GPa, H between 0.10-1.03
      GPa for the Coscinodiscus sp.; and E between 13.7-18.6 GPa, H between 0.85-1.41
      GPa for the Synedra sp.). Additionally, the mechanical response of diatom
      structures to uniform compression was examined. Predictive simulations were
      performed on the aforementioned diatom frustules, as well as another diatom
      structure (pennate Fragilariopsis kerguelensis), to correlate the mechanical
      response with specific morphology variables (e.g., pore or slit sizes). Results
      from calculated von Mises stress and displacement distributions unveil unique
      information on the effect that uniform loads have on these frustules, which can
      aid the design of tailored nanotemplates. A correlation between mechanical
      properties and porosity was established for selected frustules, and reported for
      the first time in this study.

PMID- 26196081
TI  - Synergistic influence of collagen I and BMP 2 drives osteogenic differentiation
      of mesenchymal stem cells: A cell microarray analysis.
AB  - Cell microarrays are a novel platform for the high throughput discovery of new
      biomaterials. By re-creating a multitude of cell microenvironments on a single
      slide, this approach can identify the optimal surface composition to drive a
      desired cell response. To systematically study the effects of molecular
      microenvironments on stem cell fate, we designed a cell microarray based on
      parallel exposure of mesenchymal stem cells (MSCs) to surface-immobilised
      collagen I (Coll I) and bone morphogenetic protein 2 (BMP 2). This was achieved
      by means of a reactive coating on a slide surface, enabling the covalent
      anchoring of Coll I and BMP 2 as microscale spots printed by a robotic contact
      printer. The surface between the printed protein spots was passivated using poly
      (ethylene glycol) bisamine 10,000Da (A-PEG). MSCs were then captured and cultured
      on array spots composed of binary mixtures of Coll I and BMP 2, followed by
      automated image acquisition and quantitative, multi-parameter analysis of
      cellular responses. Surface compositions that gave the highest osteogenic
      differentiation were determined using Runx2 expression and calcium deposition.
      Quantitative single cell analysis revealed subtle concentration-dependent effects
      of surface-immobilised proteins on the extent of osteogenic differentiation
      obscured using conventional analysis. In particular, the synergistic interaction
      of Coll I and BMP 2 in supporting osteogenic differentiation was confirmed. Our
      studies demonstrate the value of cell microarray platforms to decipher the
      combinatorial interactions at play in stem cell niche microenvironments. 

PMID- 26196082
TI  - A mixed-methods approach to systematic reviews.
AB  - There are an increasing number of published single-method systematic reviews that
      focus on different types of evidence related to a particular topic. As policy
      makers and practitioners seek clear directions for decision-making from
      systematic reviews, it is likely that it will be increasingly difficult for them
      to identify 'what to do' if they are required to find and understand a plethora
      of syntheses related to a particular topic.Mixed-methods systematic reviews are
      designed to address this issue and have the potential to produce systematic
      reviews of direct relevance to policy makers and practitioners.On the basis of
      the recommendations of the Joanna Briggs Institute International Mixed Methods
      Reviews Methodology Group in 2012, the Institute adopted a segregated approach to
      mixed-methods synthesis as described by Sandelowski et al., which consists of
      separate syntheses of each component method of the review. Joanna Briggs
      Institute's mixed-methods synthesis of the findings of the separate syntheses
      uses a Bayesian approach to translate the findings of the initial quantitative
      synthesis into qualitative themes and pooling these with the findings of the
      initial qualitative synthesis. 

PMID- 26196083
TI  - Meta-analysis and the problem of inconsistent effects.

PMID- 26196084
TI  - Cervical Preparation Before Dilation and Evacuation Using Adjunctive Misoprostol
      or Mifepristone Compared With Overnight Osmotic Dilators Alone: A Randomized
      Controlled Trial.
AB  - OBJECTIVE: To evaluate operative time after adjunctive misoprostol or
      mifepristone compared with overnight osmotic dilators alone for cervical
      preparation before dilation and evacuation at 16-23 6/7 weeks of gestation.
      METHODS: This double-blind, three-arm, multicenter, randomized trial compared
      overnight osmotic dilators alone, dilators plus 400 micrograms buccal misoprostol
      3 hours preoperatively, and dilators plus 200 mg oral mifepristone during dilator
      placement for dilation and evacuation. Our primary outcome was dilation and
      evacuation operative time within two cohorts: 16-18 6/7 weeks of gestation
      (N=150) and 19-23 6/7 weeks of gestation (N=150). Three hundred women were
      required for 80% power to detect a 2-minute difference in operative time.
      Secondary outcomes included initial cervical dilation, side effects, physician
      satisfaction by Likert scale, and complications. RESULTS: Between February 2013
      and February 2014 we randomized 300 women evenly across treatment arms. Group
      demographics were similar. We found no difference in operative time in either
      gestational cohort (early cohort [minutes]: 5.11+/-3.0 dilators alone, 4.99+/-3.3
      misoprostol, 4.33+/-2.0 mifepristone, P=.34; late cohort [minutes]: 7.50+/-3.7
      dilators alone, 7.62+/-5.4 misoprostol, 6.74+/-3.2 mifepristone, P=.53). In the
      early cohort, initial dilation was greater with misoprostol than dilators alone
      (2.4 compared with 2.0 cm, P=.007). Patients given misoprostol had significantly
      more pain, fever, and chills. In the late cohort, dilation and evacuation
      procedures were less difficult after mifepristone (4.1%, 95% confidence interval
      [CI] 0.0-9.6) than misoprostol (18.8%, 95% CI 7.7-29.8) or dilators alone (18.8%,
      95% CI 7.7-29.8; P=.04). We had inadequate power to infer differences in
      complications: dilators alone (10%, 95% CI 4.2-16.0) compared with misoprostol
      (2%, 95% CI 0-4.7) compared with mifepristone (2%, 95% CI 0-4.8). CONCLUSION:
      Despite no difference in operative time, adjunctive mifepristone facilitates
      later dilation and evacuation compared with osmotic dilators alone and is better
      tolerated than misoprostol. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      www.clinicaltrials.gov, NCT01751087. LEVEL OF EVIDENCE: I.

PMID- 26196086
TI  - Computer and microswitch-based programs to improve academic activities by six
      children with cerebral palsy.
AB  - This study was aimed at extending the use of assistive technology (i.e.
      microswitch such as a pressure sensor, interface and laptop) with a new setup,
      allowing six children with cerebral palsy and extensive motor disabilities to
      improve their academic activities during classroom. A second objective of the
      study was to assess a maintenance/generalization phase, occurring three months
      after the end of the intervention, at participants' homes, involving their
      parents. A third purpose of the study was to monitor the effects of the
      intervention program on the indices of positive participations (i.e. constructive
      engagement) of participants involved. Finally, a social validation procedure
      involving 36 support teachers as raters was conducted. The study was carried out
      according to a multiple probe design across behaviours followed by
      maintenance/generalization phase for each participant. That is, the two
      behaviours (i.e. choice among academic disciplines and literacy) were learned
      first singly, then combined together. Results showed an increasing of the
      performances for all participants involved during intervention phases.
      Furthermore, during maintenance phase participants consolidated their results.
      Moreover, positive participation augmented as well. Support teachers, involved in
      the social validation assessment, considered the combined intervention as more
      favourable with respect to those singly learned. Clinical, educational and
      practical implications of the findings are discussed. 

PMID- 26196085
TI  - Identification of prostate cancer biomarkers in urinary exosomes.
AB  - Exosomes have recently appeared as a novel source of non-invasive cancer
      biomarkers since tumour-specific molecules can be found in exosomes isolated from
      biological fluids. We have here investigated the proteome of urinary exosomes by
      using mass spectrometry to identify proteins differentially expressed in prostate
      cancer patients compared to healthy male controls. In total, 15 control and 16
      prostate cancer samples of urinary exosomes were analyzed. Importantly, 246
      proteins were differentially expressed in the two groups. The majority of these
      proteins (221) were up-regulated in exosomes from prostate cancer patients. These
      proteins were analyzed according to specific criteria to create a focus list that
      contained 37 proteins. At 100% specificity, 17 of these proteins displayed
      individual sensitivities above 60%. Even though several of these proteins showed
      high sensitivity and specificity for prostate cancer as individual biomarkers,
      combining them in a multi-panel test has the potential for full differentiation
      of prostate cancer from non-disease controls. The highest sensitivity, 94%, was
      observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame
      61). LAMTOR proteins were also distinctly enriched with very high specificity for
      patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to
      100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid
      subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class
      members and proteasomal proteins. In conclusion, this study clearly shows the
      potential of using urinary exosomes in the diagnosis and clinical management of
      prostate cancer. 

PMID- 26196087
TI  - Biologically inspired information theory: Adaptation through construction of
      external reality models by living systems.
AB  - Higher animals act in the world using their external reality models to cope with
      the uncertain environment. Organisms that have not developed such information
      processing organs may also have external reality models built in the form of
      their biochemical, physiological, and behavioral structures, acquired by natural
      selection through successful models constructed internally. Organisms subject to
      illusions would fail to survive in the material universe. How can organisms, or
      living systems in general, determine the external reality from within? This paper
      starts with a phenomenological model, in which the self constitutes a reality
      model developed through the mental processing of phenomena. Then, the it-from-bit
      concept is formalized using a simple mathematical model. For this formalization,
      my previous work on an algorithmic process is employed to constitute symbols
      referring to the external reality, called the inverse causality, with additional
      improvements to the previous work. Finally, as an extension of this model, the
      cognizers system model is employed to describe the self as one of many material
      entities in a world, each of which acts as a subject by responding to the
      surrounding entities. This model is used to propose a conceptual framework of
      information theory that can deal with both the qualitative (semantic) and
      quantitative aspects of the information involved in biological processes. 

PMID- 26196088
TI  - Pragmatic phenomenological types.
AB  - We approach a well-known problem: how to relate component physical processes in
      biological systems to governing imperatives in multiple system levels. The intent
      is to further practical tools that can be used in the clinical context. An
      example proposes a formal type system that would support this kind of reasoning,
      including in machines. Our example is based on a model of the connection between
      a quality of mind associated with creativity and neuropsychiatric dynamics:
      constructing narrative as a form of conscious introspection, which allows the
      manipulation of one's own driving imperatives. In this context, general
      creativity is indicated by an ability to manage multiple heterogeneous worldviews
      simultaneously in a developing narrative. 'Narrative' in this context is framed
      as the organizing concept behind rational linearization that can be applied to
      metaphysics as well as modeling perceptive dynamics. Introspection is framed as
      the phenomenological 'tip' that allows a perceiver to be within experience or
      outside it, reflecting on and modifying it. What distinguishes the approach is
      the rooting in well founded but disparate disciplines: phenomenology, ontic
      virtuality, two-sorted geometric logics, functional reactive programming, multi
      level ontologies and narrative cognition. This paper advances the work by
      proposing a type strategy within a two-sorted reasoning system that supports
      cross-ontology structure. The paper describes influences on this approach, and
      presents an example that involves phenotype classes and monitored creativity
      enhanced by both soft methods and transcranial direct-current stimulation. The
      proposed solution integrates pragmatic phenomenology, situation theory,
      narratology and functional programming in one framework. 

PMID- 26196089
TI  - A novel titania/calcium silicate hydrate hierarchical coating on titanium.
AB  - Recently, surface micron/nano-topographical modifications have attracted a great
      deal of attention because it is capable of mimicking the hierarchical
      characteristics of bone. In the current work, a novel titania/calcium silicate
      hydrate (CSH) bi-layer coating with hierarchical surface topography was
      successfully prepared on titanium substrate through micro-arc oxidation (MAO) and
      subsequent hydrothermal treatment (HT). MAO treatment could lead to a micron
      scale topographical surface with numerous crater-like protuberances. The
      subsequent HT process enables the in situ nucleation and growth of CSH nanoplates
      on MAO-fabricated titania surface. The nucleation of CSH nanoplates is considered
      to follow a dissolution-precipitation mechanism. Compared to MAO-fabricated
      coating with single-scale surface topography, MAO-HT-fabricated coating with
      hierarchical surface topography exhibits enhanced hydrophilicity, fibronectin
      adsorption and initial MG-63 cell attachment. The process of cell-material
      interactions is considered to be triggered by surface properties of the coated
      layer and indirectly mediated by protein adsorption on coating surface. These
      results suggest that MAO-HT treatment is an efficient way to prepare coatings
      with hierarchical surface topography on titanium surface, which is essential for
      altering protein adsorption and initial cell attachment. 

PMID- 26196090
TI  - Bovine alpha-lactalbumin functionalized graphene oxide nano-sheet exhibits
      enhanced biocompatibility: A rational strategy for graphene-based targeted cancer
      therapy.
AB  - Graphene oxide nanosheet (GOns) with sharp edges was synthesized using controlled
      pyrolysis of citric acid. Scanning electron, as well as atomic force microscopy
      of the sample confirmed the formation of multilayered GOns with an average sheet
      length of 150 nm. X-ray diffraction pattern and Raman spectra also confirmed the
      formation of GOns. Furthermore, GOns was successfully functionalized (FGOns) by
      cross-linking with a small protein bovine alpha-lactalbumin (BLA). The
      crosslinking of protein with GOns in FGOns was confirmed by infrared
      spectroscopy, and the conformational change of BLA was observed by fluorescence,
      as well as circular dichroism spectroscopy. When applied to human erythrocytes,
      GOns demonstrated profound hemolysis; however, such hemolytic effect was
      drastically reduced by FGOns. To evaluate the potential biomedical application of
      FGOns, the cytotoxicity of the sample was also assessed. The administration of
      both GOns and FGOns in breast cancer cells MCF-7 and MDAMB-231 demonstrated more
      than 88% cell death within 24 h and such cytotoxicity against cancer cells was
      caused due to the generation of reactive oxygen species (ROS), as revealed from
      the N-acetyl-L-cysteine (NAC, a ROS-inhibitor)-based assay. FGOns demonstrated
      excellent biocompatibility against normal cells such as HaCaT and 3T3 compared to
      GOns that demonstrated dose-dependent toxicity. Moreover, FGOns demonstrated more
      efficient cellular uptake than GOns by cancer cells. Therefore, our present study
      demonstrated that the functionalization of GOns using small protein could improve
      its biocompatibility multifold and such strategy might represent wide opportunity
      to use GO like nanomaterial safely in various biomedical applications.

PMID- 26196091
TI  - Synthesis of multi-functional nanocapsules via interfacial AGET ATRP in
      miniemulsion for tumor micro-environment responsive drug delivery.
AB  - Novel multi-functional polymeric hollow nanocapsules (PHN) based on the
      crosslinked poly(tert-butyl acrylate) (PtBA) shells were synthesized in a
      miniemulsion interfacial polymerization via activator generated electron transfer
      atom transfer radical polymerization (AGET ATRP) technique with N,N'
      bis(acryloyl) cystamine (BACy) as cross-linking agent, CuBr2 as catalyst,
      ascorbic acid (VC) as reducing agent and hexadecane as inert solvent. In the AGET
      ATRP, a folate-conjugated block copolymer, folate-poly(ethylene glycol)-b
      poly(tert-butyl acrylate) (FA-PEG-tBA-Br), was used as macroinitiator/stabilizer,
      and the specific amphiphilic nature of the copolymer led the extending inward of
      polymer chains. The DLS analysis directly showed the PHN with an average diameter
      of 150 nm was obtained. After the PtBA shells were transformed into poly(acrylic
      acid) (PAA) by hydrolysis, doxorubicin (DOX), as a model drug, was loaded
      efficiently into the hydrolyzed polymeric hollow nanocapsules (HPHN), then the in
      vitro release of drug was carried out in phosphate buffer solution (PBS, pH 7.4
      or 5.0, with or without DTT or GSH of different concentrations). It showed that
      the existence of folate group significantly improved pH stimuli-responsive and
      DOX-loading capacity of the polymeric nanocapsules. An acidic pH (5.0) and
      presence of GSH would accelerate the DOX release behavior. Thus, these multi
      functional polymeric nanocapsules have excellent available properties in the
      field of targeted and controlled drug delivery for cancer therapy.

PMID- 26196092
TI  - Effect of immobilized collagen type IV on biological properties of endothelial
      cells for the enhanced endothelialization of synthetic vascular graft materials.
AB  - Regeneration of healthy endothelium onto vascular graft materials is imperative
      for prevention of intimal hyperplasia and thrombogenesis. In this study, we
      investigated the effect of collagen type IV (COL-IV) immobilized onto electrospun
      nanofibers on modulation of endothelial cell (EC) function, as a potential signal
      to rapid endothelialization of vascular grafts. COL-IV is assembled in basement
      membrane underneath intimal layer and regulates morphogenesis of blood vessels.
      For immobilization of COL-IV, poly(l-lactic acid) (PLLA) nanofibers (PL) were
      prepared as a model vascular graft substrate, onto which acrylic acid (AAc) was
      then grafted by using gamma-ray irradiation. AAc graft was dependent on
      irradiation doses and AAc concentrations, which allowed us to select the
      condition of 5% (v/v) AAc and 10 kGy for further conjugation of COL-IV. COL-IV
      immobilization was proportionally controlled as a function of its concentration.
      Atomic force microscope (AFM) analysis qualitatively supported immobilization of
      COL-IV, demonstrating increase in root mean square roughness of the PL from
      665.37 +/- 13.20 nm to 1440.74 +/- 33.24. However, the Young's modulus of
      nanofibers was retained as approximately 1 MPa, regardless of surface
      modification. The number of ECs attached on the nanofibers with immobilized COL
      IV was significantly increased by 5 times (1052 +/- 138 cells/mm(2)) from
      pristine PL (234 +/- 41 cells/mm(2)). In addition, the effect of immobilized COL
      IV was profound for enhancing proliferation and up-regulation of markers
      implicated in rapid endothelialization. Collectively, our results suggest that
      COL-IV immobilized onto electrospun PLLA nanofibers may serve as a promising
      instructive cue used in vascular graft materials.

PMID- 26196093
TI  - Antimicrobial behavior of novel surfaces generated by electrophoretic deposition
      and breakdown anodization.
AB  - Biofilms have devastating impacts on many industries such as increased fuel
      consumption and damage to surfaces in maritime industries. Ideal biofouling
      management is inhibition of initial bacterial attachment. The attachment of a
      model marine bacterium (Halomonas pacfica g) was investigated to evaluate the
      potential of these new novel surfaces to resist initial bacterial adhesion. Novel
      engineered surfaces were generated via breakdown anodization or electrophoretic
      deposition, to modify three parameters: hydrophobicity, surface chemistry, and
      roughness. Mass transfer rates were determined using a parallel plate flow
      chamber under relevant solution chemistries. The greatest deposition was observed
      on the superhydrophilic surface, which had micro- and nano-scale hierarchical
      structures composed of titanium oxide deposited on a titanium plate. Conversely,
      one of the hydrophobic surfaces with micro-porous films overlaid with
      polydimethylsiloxane appeared to be most resistant to cell attachment. 

PMID- 26196094
TI  - Insight on how fishing bats discern prey and adjust their mechanic and sensorial
      features during the attack sequence.
AB  - Several insectivorous bats have included fish in their diet, yet little is known
      about the processes underlying this trophic shift. We performed three field
      experiments with wild fishing bats to address how they manage to discern fish
      from insects and adapt their hunting technique to capture fish. We show that bats
      react only to targets protruding above the water and discern fish from insects
      based on prey disappearance patterns. Stationary fish trigger short and shallow
      dips and a terminal echolocation pattern with an important component of the
      narrowband and low frequency calls. When the fish disappears during the attack
      process, bats regulate their attack increasing the number of broadband and high
      frequency calls in the last phase of the echolocation as well as by lengthening
      and deepening their dips. These adjustments may allow bats to obtain more
      valuable sensorial information and to perform dips adjusted to the level of
      uncertainty on the location of the submerged prey. The observed ultrafast
      regulation may be essential for enabling fishing to become cost-effective in
      bats, and demonstrates the ability of bats to rapidly modify and synchronise
      their sensorial and motor features as a response to last minute stimulus
      variations. 

PMID- 26196095
TI  - Lessons learned from family history in ocular genetics.
AB  - PURPOSE OF REVIEW: Given the vast genetic and phenotypic heterogeneity seen in
      ocular genetic disorders, considering a patient's clinical phenotype in the
      context of the family history is essential. RECENT FINDINGS: Clinicians can
      improve patient care by appropriately incorporating a patient's family history
      into their evaluation. Obtaining, reviewing, and accurately interpreting the
      pedigree are skills geneticists and genetic counselors possess. However, with the
      field of ophthalmic genetics vastly growing, it is becoming essential for
      ophthalmologists to understand the utility of the pedigree and develop their
      abilities in eliciting this information. By not considering a patient's clinical
      history in the context of the family history, diagnoses can be missed or
      inaccurate. SUMMARY: The purpose of this review is to inform ophthalmologists on
      the importance of the family history and highlight how the pedigree can aid in
      establishing an accurate genetic diagnosis. This review also provides to
      ophthalmologists helpful tips on eliciting and interpreting a patient's family
      history.

PMID- 26196096
TI  - Is there anything new in strabismus?

PMID- 26196097
TI  - Achromatopsia: a review.
AB  - PURPOSE OF REVIEW: The purposes of this article are to examine the literature
      published on achromatopsia and provide a comprehensive review of the clinical
      disease, genetic characteristics, and potential for therapy. Specifically, this
      article will describe recent advances in gene therapy in animal models, clinical
      features in human, and barriers to human translation. RECENT FINDINGS: Building
      on prior success with adeno-associated virus (AAV) therapy in mice models for
      achromatopsia with mutations in the CNGB3, CNGA3, or GNAT2 genes, multiple cone
      specific promoters have recently been developed and shown success in mice and
      nonhuman primates. A sheep CNGA3 model has also been characterized. Two clinical
      trials are under way: one to better characterize humans with achromatopsia and
      another to study a ciliary neurotrophic factor (CNTF) implant as a treatment for
      patients with the CNGB3 mutation. SUMMARY: Genetic understanding and disease
      characterization of achromatopsia continues to evolve, as do gene therapy tools
      and animal models. The potential for the treatment of achromatopsia in humans
      with gene therapy shows great promise.

PMID- 26196098
TI  - Development of Framework for Assessing Influenza Virus Pandemic Risk.
AB  - Although predicting which influenza virus subtype will cause the next pandemic is
      not yet possible, public health authorities must continually assess the pandemic
      risk associated with animal influenza viruses, particularly those that have
      caused infections in humans, and determine what resources should be dedicated to
      mitigating that risk. To accomplish this goal, a risk assessment framework was
      created in collaboration with an international group of influenza experts.
      Compared with the previously used approach, this framework, named the Influenza
      Risk Assessment Tool, provides a systematic and transparent approach for
      assessing and comparing threats posed primarily by avian and swine influenza
      viruses. This tool will be useful to the international influenza community and
      will remain flexible and responsive to changing information. 

PMID- 26196099
TI  - Bronchiolectasis due to giant thoracic vertebral osteophytes.

PMID- 26196100
TI  - Trabeculated thoracic spine lesion with paraparesis.

PMID- 26196101
TI  - Cervical myelopathy caused by anomalies at the craniovertebral junction.

PMID- 26196102
TI  - Unilateral absence of the neural arch in the subaxial cervical spine.

PMID- 26196103
TI  - Isolated traumatic craniovertebral junction subdural hematoma.

PMID- 26196104
TI  - Bilateral lumbar pedicle fractures in the absence of a neurologic deficit or
      concomitant osseous injury.

PMID- 26196105
TI  - The adolescent multiple spondylolysis associated with spondylolisthesis in the
      upper lumbar vertebrae.

PMID- 26196106
TI  - Drivers of Emerging Infectious Disease Events as a Framework for Digital
      Detection.
AB  - The growing field of digital disease detection, or epidemic intelligence,
      attempts to improve timely detection and awareness of infectious disease (ID)
      events. Early detection remains an important priority; thus, the next frontier
      for ID surveillance is to improve the recognition and monitoring of drivers
      (antecedent conditions) of ID emergence for signals that precede disease events.
      These data could help alert public health officials to indicators of elevated ID
      risk, thereby triggering targeted active surveillance and interventions. We
      believe that ID emergence risks can be anticipated through surveillance of their
      drivers, just as successful warning systems of climate-based, meteorologically
      sensitive diseases are supported by improved temperature and precipitation data.
      We present approaches to driver surveillance, gaps in the current literature, and
      a scientific framework for the creation of a digital warning system. Fulfilling
      the promise of driver surveillance will require concerted action to expand the
      collection of appropriate digital driver data. 

PMID- 26196107
TI  - Macrolide-Resistant Mycoplasma pneumoniae, United States.
AB  - Macrolide-resistant Mycoplasma pneumoniae (MRMP) is highly prevalent in Asia and
      is now being reported from Europe. Few data on MRMP are available in the United
      States. Using genotypic and phenotypic methods, we detected high-level MRMP in
      13.2% of 91 M. pneumoniae--positive specimens from 6 US locations. 

PMID- 26196109
TI  - The Nature of Culture: an eight-grade model for the evolution and expansion of
      cultural capacities in hominins and other animals.
AB  - Tracing the evolution of human culture through time is arguably one of the most
      controversial and complex scholarly endeavors, and a broad evolutionary analysis
      of how symbolic, linguistic, and cultural capacities emerged and developed in our
      species is lacking. Here we present a model that, in broad terms, aims to explain
      the evolution and portray the expansion of human cultural capacities (the EECC
      model), that can be used as a point of departure for further multidisciplinary
      discussion and more detailed investigation. The EECC model is designed to be
      flexible, and can be refined to accommodate future archaeological,
      paleoanthropological, genetic or evolutionary psychology/behavioral analyses and
      discoveries. Our proposed concept of cultural behavior differentiates between
      empirically traceable behavioral performances and behavioral capacities that are
      theoretical constructs. Based largely on archaeological data (the 'black box'
      that most directly opens up hominin cultural evolution), and on the extension of
      observable problem-solution distances, we identify eight grades of cultural
      capacity. Each of these grades is considered within evolutionary-biological and
      historical-social trajectories. Importantly, the model does not imply an
      inevitable progression, but focuses on expansion of cultural capacities based on
      the integration of earlier achievements. We conclude that there is not a single
      cultural capacity or a single set of abilities that enabled human culture;
      rather, several grades of cultural capacity in animals and hominins expanded
      during our evolution to shape who we are today. 

PMID- 26196108
TI  - Yindanxinnaotong, a Chinese compound medicine, synergistically attenuates
      atherosclerosis progress.
AB  - Yindanxinnaotong (YD), a traditional Chinese medicine, has been introduced to
      clinical medicine for more than a decade, while its pharmacological properties
      are still not to be well addressed. This report aimed to explore the anti
      atherosclerosis properties and underlying mechanisms of YD. We initially
      performed a computational prediction based on a network pharmacology simulation,
      which clued YD exerted synergistically anti-atherosclerosis properties by
      vascular endothelium protection, lipid-lowering, anti-inflammation, and anti
      oxidation. These outcomes were then validated in atherosclerosis rats. The
      experiments provided evidences indicating YD's contribution in this study
      included, (1) significantly reduced the severity of atherosclerosis, inhibited
      reconstruction of the artery wall and regulated the lipid profile; (2) enhanced
      antioxidant power, strengthened the activity of antioxidant enzymes, and
      decreased malondialdhyde levels; (3) significantly increased the viability of
      umbilical vein endothelial cells exposed to oxidative stress due to pretreatment
      with YD; (4) significantly reduced the level of pro-inflammatory cytokines; (5)
      significantly down-regulated NF-kB/p65 and up-regulated IkB in the YD-treated
      groups. Overall, these results demonstrated that YD intervention relieves
      atherosclerosis through regulating lipids, reducing lipid particle deposition in
      the endothelial layer of artery, enhancing antioxidant power, and repressing
      inflammation activity by inhibiting the nuclear factor-kappa B signal pathway. 

PMID- 26196116
TI  - Three hands: one year later.

PMID- 26196117
TI  - Homogeneous sulfopeptides and sulfoproteins: synthetic approaches and
      applications to characterize the effects of tyrosine sulfation on biochemical
      function.
AB  - Post-translational modification of proteins plays critical roles in regulating
      structure, stability, localization, and function. Sulfation of the phenolic side
      chain of tyrosine residues to form sulfotyrosine (sTyr) is a widespread
      modification of extracellular and integral membrane proteins, influencing the
      activities of these proteins in cellular adhesion, blood clotting, inflammatory
      responses, and pathogen infection. Tyrosine sulfation commonly occurs in
      sequences containing clusters of tyrosine residues and is incomplete at each
      site, resulting in heterogeneous mixtures of sulfoforms. Purification of
      individual sulfoforms is typically impractical. Therefore, the most promising
      approach to elucidate the influence of sulfation at each site is to prepare
      homogeneously sulfated proteins (or peptides) synthetically. This Account
      describes our recent progress in both development of such synthetic approaches
      and application of the resulting sulfopeptides and sulfoproteins to characterize
      the functional consequences of tyrosine sulfation. Initial synthetic studies used
      a cassette-based solid-phase peptide synthesis (SPPS) approach in which the side
      chain sulfate ester was protected to enable it to withstand Fmoc-based SPPS
      conditions. Subsequently, to address the need for efficient access to multiple
      sulfoforms of the same peptide, we developed a divergent solid-phase synthetic
      approach utilizing orthogonally side chain protected tyrosine residues. Using
      this methodology, we have carried out orthogonal deprotection and sulfation of up
      to three tyrosine residues within a given sequence, allowing access to all eight
      sulfoforms of a given target from a single solid-phase synthesis. With
      homogeneously sulfated peptides in hand, we have been able to probe the influence
      of tyrosine sulfation on biochemical function. Several of these studies focused
      on sulfated fragments of chemokine receptors, key mediators of leukocyte
      trafficking and inflammation. For the receptor CCR3, we showed that tyrosine
      sulfation enhances affinity and selectivity for binding to chemokine ligands, and
      we determined the structural basis of these affinity enhancements by NMR
      spectroscopy. Using a library of CCR5 sulfopeptides, we demonstrated the critical
      importance of sulfation at one specific site for supporting HIV-1 infection.
      Demonstrating the feasibility of producing homogeneously tyrosine-sulfated
      proteins, in addition to smaller peptides, we have used SPPS and native chemical
      ligation methods to synthesize the leech-derived antithrombotic protein hirudin
      P6, containing both tyrosine sulfation and glycosylation. Sulfation greatly
      enhanced inhibitory activity against thrombin, whereas addition of glycans to the
      sulfated protein decreased inhibition, indicating functional interplay between
      different post-translational modifications. In addition, the success of the
      ligation approach suggests that larger sulfoproteins could potentially be
      obtained by ligation of synthetic sulfopeptides to expressed proteins, using
      intein-based technology. 

PMID- 26196118
TI  - Cavitating Lung Disease: A Novel Presentation of IgG4-Related Disease.
AB  - BACKGROUND: Immunoglobulin (Ig) G4-related disease, previously referred to as
      IgG4-related sclerosing disease or hyper-IgG4 disease, may occur in the lung,
      involving alveolar parenchyma, airways, and pleura. Various pulmonary
      manifestations of IgG4-related disease have been reported, but to the best of our
      knowledge a cavitating lung disease has not been reported previously. CASE
      REPORT: We describe a 60-year-old man who presented with hemoptysis and
      cavitating lung disease with clinical, laboratory, and histopathologic findings
      compatible with IgG4-related disease. Other potential causes of cavitation were
      excluded. Treatment was initiated with oral prednisone and subsequently
      mycophenolate mofetil was added. Follow-up 1 year later shows stable pulmonary
      function with complete resolution of the cavitary lesions. CONCLUSIONS: We
      present a case of cavitating lung disease as a previously unreported
      manifestation of IgG4-related disease. Our patient had an excellent response to
      immunosuppression. An increased awareness of IgG4-related disease and its myriad
      of manifestations is very important for pulmonologists.

PMID- 26196119
TI  - Nanoparticles with photoinduced precipitation for the extraction of pollutants
      from water and soil.
AB  - Nanotechnology may offer fast and effective solutions for environmental clean-up.
      Herein, amphiphilic diblock copolymers are used to develop a platform of
      photosensitive core-shell nanoparticles. Irradiation with ultraviolet light
      removes the protective layer responsible for colloidal stability; as a result,
      the nanoparticles are rapidly and irreversibly converted to macroscopic
      aggregates. The associated phase separation allows measuring the partitioning of
      small molecules between the aqueous phase and nanoparticles; data suggests that
      interactions are enhanced by decreasing the particle size. Adsorption onto
      nanoparticles can be exploited to efficiently remove hydrophobic pollutants from
      water and contaminated soil. Preliminary in vivo experiments suggest that
      treatment with photocleavable nanoparticles can significantly reduce the
      teratogenicity of bisphenol A, triclosan and 17alpha-ethinyl estradiol without
      generating obviously toxic byproducts. Small-scale pilot experiments on
      wastewater, thermal printing paper and contaminated soil demonstrate the
      applicability of the approach. 

PMID- 26196120
TI  - Recent progress in the development of protein-protein interaction inhibitors
      targeting androgen receptor-coactivator binding in prostate cancer.
AB  - The androgen receptor (AR) is a key regulator for the growth, differentiation and
      survival of prostate cancer cells. Identified as a primary target for the
      treatment of prostate cancer, many therapeutic strategies have been developed to
      attenuate AR signaling in prostate cancer cells. While frontline androgen
      deprivation therapies targeting either the production or action of androgens
      usually yield favorable responses in prostate cancer patients, a significant
      number acquire treatment resistance. Known as the castration-resistant prostate
      cancer (CRPC), the treatment options are limited for this advanced stage. It has
      been shown that AR signaling is restored in CRPC due to many aberrant mechanisms
      such as AR mutations, amplification or expression of constitutively active splice
      variants. Coregulator recruitment is a crucial regulatory step in AR signaling
      and the direct blockade of coactivator binding to AR offers the opportunity to
      develop therapeutic agents that would remain effective in prostate cancer cells
      resistant to conventional endocrine therapies. Structural analyses of the AR have
      identified key surfaces involved in protein-protein interaction with coregulators
      that have been recently used to design and develop promising AR-coactivator
      binding inhibitors. In this review we will discuss the design and development of
      small-molecule inhibitors targeting the AR-coactivator interactions for the
      treatment of prostate cancer.

PMID- 26196121
TI  - The effect of fetal growth and nutrient stresses on steroid pathways.
AB  - The early life environment is a crucial time for establishing the trajectory of
      future health. Low birthweight is considered a marker of an adverse in utero
      environment and predisposes to cardio-metabolic disease later in life. It has
      been proposed that this is mediated by glucocorticoids, with life-long activation
      of the HPA axis. Here we review the evidence to support this hypothesis, with
      particular emphasis on the effects of fetal growth and nutrient stresses in utero
      on steroid pathways of the HPA axis. A better understanding of the mechanisms
      underlying these processes could help to optimize in utero health, and identify
      individuals at greatest risk of future disease.

PMID- 26196122
TI  - Inhibition of pulmonary adenoma in diethylnitrosamine-induced rats by Rhizoma
      paridis saponins.
AB  - Nowadays, people pay more and more attention to the natural products based on
      their multiple targets in the antitumor treatment. In our previous research,
      Rhizoma paridis saponins (RPS) were regarded as potent anticancer agent that
      elicits programmed cell death and inhibits metastases in murine lung
      adenocarcinoma in vivo. In the present study, we set up a rat model of
      diethylnitrosamine (DEN) induced pulmonary adenoma to evaluate the antitumor
      effects of RPS again. After 20 weeks treatment, rats were sacrificed in order to
      perform histopathological examinations, blood biochemistry, immunohistochemistry,
      western blot, PCR and metabonomics. As a result, DEN induced pulmonary adenoma
      generation in the lungs and damaged hepatocytes and hepatoma formation in the
      livers. RPS effectively attenuated hepatotoxic and inhibited pulmonary adenoma
      through down-regulating expression of MMP-9 and up-regulating level of TIMP-2 in
      DEN-induced rats. Meanwhile, RPS remarkably decreased energy metabolism, and
      glycine, serine and threonine metabolism to block the tumor growth. In
      conclusion, RPS would be a potent anticancer agent used in the prospective
      application. 

PMID- 26196124
TI  - An M/M/c/K State-Dependent Model for Pedestrian Flow Control and Design of
      Facilities.
AB  - Pedestrian overflow causes queuing delay and in turn, is controlled by the
      capacity of a facility. Flow control or blocking control takes action to avoid
      queues from building up to extreme values. Thus, in this paper, the problem of
      pedestrian flow control in open outdoor walking facilities in equilibrium
      condition is investigated using M/M/c/K queuing models. State dependent service
      rate based on speed and density relationship is utilized. The effective rate of
      the Poisson arrival process to the facility is determined so as there is no
      overflow of pedestrians. In addition, the use of the state dependent queuing
      models to the design of the facilities and the effect of pedestrian personal
      capacity on the design and the traffic congestion are discussed. The study does
      not validate the sustainability of adaptation of Western design codes for the
      pedestrian facilities in the countries like Bangladesh.

PMID- 26196123
TI  - Comparative Phytochemical Analysis of Essential Oils from Different Biological
      Parts of Artemisia herba alba and Their Cytotoxic Effect on Cancer Cells.
AB  - PURPOSE: Carrying out the chemical composition and antiproliferative effects
      against cancer cells from different biological parts of Artemisia herba alba.
      METHODS: Essential oils were studied by gas chromatography coupled to mass
      spectrometry (GC-MS) and their antitumoral activity was tested against P815
      mastocytoma and BSR kidney carcinoma cell lines; also, in order to evaluate the
      effect on normal human cells, oils were tested against peripheral blood
      mononuclear cells PBMCs. RESULTS: Essential oils from leaves and aerial parts
      (mixture of capitulum and leaves) were mainly composed by oxygenated
      sesquiterpenes 39.89% and 46.15% respectively; capitulum oil contained
      essentially monoterpenes (22.86%) and monocyclic monoterpenes (21.48%); esters
      constituted the major fraction (62.8%) of stem oil. Essential oils of different
      biological parts studied demonstrated a differential antiproliferative activity
      against P815 and BSR cancer cells; P815 cells are the most sensitive to the
      cytotoxic effect. Leaves and capitulum essential oils are more active than aerial
      parts. Interestingly, no cytotoxic effect of these essential oils was observed on
      peripheral blood mononuclear cells. CONCLUSION: Our results showed that the
      chemical composition variability of essential oils depends on the nature of
      botanical parts of Artemisia herba alba. Furthermore, we have demonstrated that
      the differential cytotoxic effect depends not only on the essential oils
      concentration, but also on the target cells and the botanical parts of essential
      oils used.

PMID- 26196125
TI  - Eukaryotic rRNA Modification by Yeast 5-Methylcytosine-Methyltransferases and
      Human Proliferation-Associated Antigen p120.
AB  - Modified nucleotide 5-methylcytosine (m5C) is frequently present in various
      eukaryotic RNAs, including tRNAs, rRNAs and in other non-coding RNAs, as well as
      in mRNAs. RNA:m5C-methyltranferases (MTases) Nop2 from S. cerevisiae and human
      proliferation-associated nucleolar antigen p120 are both members of a protein
      family called Nop2/NSUN/NOL1. Protein p120 is well-known as a tumor marker which
      is over-expressed in various cancer tissues. Using a combination of RNA bisulfite
      sequencing and HPLC-MS/MS analysis, we demonstrated here that p120 displays an
      RNA:m5C- MTase activity, which restores m5C formation at position 2870 in domain
      V of 25S rRNA in a nop2Delta yeast strain. We also confirm that yeast proteins
      Nop2p and Rcm1p catalyze the formation of m5C in domains V and IV, respectively.
      In addition, we do not find any evidence of m5C residues in yeast 18S rRNA. We
      also performed functional complementation of Nop2-deficient yeasts by human p120
      and studied the importance of different sequence and structural domains of Nop2
      and p120 for yeast growth and m5C-MTase activity. Chimeric protein formed by Nop2
      and p120 fragments revealed the importance of Nop2 N-terminal domain for correct
      protein localization and its cellular function. We also validated that the
      presence of Nop2, rather than the m5C modification in rRNA itself, is required
      for pre-rRNA processing. Our results corroborate that Nop2 belongs to the large
      family of pre-ribosomal proteins and possesses two related functions in pre-rRNA
      processing: as an essential factor for cleavages and m5C:RNA:modification. These
      results support the notion of quality control during ribosome synthesis by such
      modification enzymes.

PMID- 26196126
TI  - Development and Psychometric Evaluation of the Chinese Feeding Difficulty Index
      (Ch-FDI) for People with Dementia.
AB  - AIMS: To develop and evaluate the psychometric properties of a Chinese Feeding
      Difficulty Index (Ch-FDI) which assesses feeding difficulties in people with
      dementia (PwD). RESEARCH DESIGN AND METHOD: Scale items were developed using
      literature review based on Model of Feeding Difficulty. Content validity was
      evaluated and items were modified by expert panel. Following translation and back
      translation, the Ch-FDI was piloted on residents with dementia. The reliability
      was tested by inter-rater reliability and test-retest reliability. Internal
      reliability was established by calculating Cronbach's alpha coefficient. The
      concurrent validity was evaluated by correlating with similar scale, the
      Edinburgh Feeding Evaluation in Dementia (EdFED). The exploratory factor analysis
      (EFA) with varimax rotation and parallel analysis (PA) was performed to test
      construct validity. METHOD: Participants were recruited from long-term care
      facilities in Taiwan. A total of 213 residents with dementia participated in this
      study during May, 2010 to February, 2011. RESULTS: Content validation,
      translation and psychometric testing were completed on the 19 items of the Ch
      FDI. The translated scale was piloted on 213 residents with dementia of feeding
      difficulty who were recruited from eight long-term care facilities in Taiwan. The
      reliability was supported by the internal consistency of Cronbach's alpha of 0.68
      and a test-retest coefficient of 0.85. The content validity, face validity,
      concurrent validity, and construct validity were used. CONCLUSIONS: The Ch-FDI is
      a newly developed scale with fair psychometric properties aimed to measure
      feeding difficulties among residents with dementia in long-term care facilities
      in Taiwan. Using this reliable and valid tool can help healthcare providers to
      assess feeding problems of PwD and provide feeding assistance in order to promote
      quality of care during mealtime in long-term care facilities.

PMID- 26196127
TI  - The Effectiveness of Conservative Management for Acute Whiplash Associated
      Disorder (WAD) II: A Systematic Review and Meta-Analysis of Randomised Controlled
      Trials.
AB  - OBJECTIVE: To evaluate the effectiveness of conservative management (except drug
      therapy) for acute Whiplash Associated Disorder (WAD) II. DESIGN: Systematic
      review and meta-analysis of Randomised Controlled Trials (RCTs) using a pre
      defined protocol. Two independent reviewers searched information sources, decided
      eligibility of studies, and assessed risk of bias (RoB) of included trials. Data
      were extracted by one reviewer and checked by the other. A third reviewer
      mediated any disagreements throughout. Qualitative trial and RoB data were
      summarised descriptively. Quantitative syntheses were conducted across trials for
      comparable interventions, outcome measures and assessment points. Meta-analyses
      compared effect sizes with random effects, using STATA version 12. DATA SOURCES:
      PEDro, Medline, Embase, AMED, CINAHL, PsycINFO, and Cochrane Library with manual
      searching in key journals, reference lists, British National Bibliography for
      Report Literature, Center for International Rehabilitation Research Information &
      Exchange, and National Technical Information Service were searched from inception
      to 15th April 2015. Active researchers in the field were contacted to determine
      relevant studies. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: RCTs evaluating
      acute (<4 weeks) WADII, any conservative intervention, with outcome measures
      important to the International Classification of Function, Disability and Health.
      RESULTS: Fifteen RCTs all assessed as high RoB (n=1676 participants) across 9
      countries were included. Meta-analyses enabled 4 intervention comparisons:
      conservative versus standard/control, active versus passive, behavioural versus
      standard/control, and early versus late. Conservative intervention was more
      effective for pain reduction at 6 months (95%CI: -20.14 to -3.38) and 1-3 years (
      25.44 to -3.19), and improvement in cervical mobility in the horizontal plane at
      <3 months (0.43 to 5.60) compared with standard/control intervention. Active
      intervention was effective for pain alleviation at 6 months (-17.19 to -3.23) and
      1-3 years (-26.39 to -10.08) compared with passive intervention. Behavioural
      intervention was more effective than standard/control intervention for pain
      reduction at 6 months (-15.37 to -1.55), and improvement in cervical movement in
      the coronal (0.93 to 4.38) and horizontal planes at 3-6 months (0.43 to 5.46).
      For early (<4 days) versus late (>10 days) interventions, there were no
      statistically significant differences in all outcome measures between
      interventions at any time. CONCLUSIONS: Conservative and active interventions may
      be useful for pain reduction in patients with acute WADII. Additionally, cervical
      horizontal mobility could be improved by conservative intervention. The
      employment of a behavioural intervention (e.g. act-as-usual, education and self
      care including regularly exercise) could have benefits for pain reduction and
      improvement in cervical movement in the coronal and horizontal planes. The
      evidence was evaluated as low/very low level according to the Grading of
      Recommendations Assessment, Development and Evaluation system.

PMID- 26196128
TI  - Establishment of a High-Throughput Assay to Monitor Influenza A Virus RNA
      Transcription and Replication.
AB  - Influenza A virus (IAV) poses significant threats to public health because of the
      recent emergence of highly pathogenic strains and wide-spread resistance to
      available anti-influenza drugs. Therefore, new antiviral targets and new drugs to
      fight influenza virus infections are needed. Although IAV RNA
      transcription/replication represents a promising target for antiviral drug
      development, no assay ideal for high-throughput screening (HTS) application is
      currently available to identify inhibitors targeting these processes. In this
      work, we developed a novel HTS assay to analyze the transcription and replication
      of IAV RNA using an A549 cell line stably expressing IAV RNA-dependent RNA
      polymerase (RdRp) complex, NP and a viral mini-genomic RNA. Both secreted Gaussia
      luciferase (Gluc) and blasticidin resistance gene (Bsd) were encoded in the viral
      minigenome and expressed under the control of IAV RdRp. Gluc serves as a reporter
      to monitor the activity of IAV RdRp, and Bsd is used to maintain the expression
      of all foreign genes. Biochemical studies and the statistical analysis presented
      herein demonstrate the high specificity, sensitivity and reproducibility of the
      assay. This work provides an ideal HTS assay for the identification of inhibitors
      targeting the function of IAV RdRp and a convenient reporting system for
      mechanism study of IAV RNA transcription / replication.

PMID- 26196129
TI  - An Experimental Test of Buffer Utility as a Technique for Managing Pool-Breeding
      Amphibians.
AB  - Vegetated buffers are used extensively to manage wetland-dependent wildlife.
      Despite widespread application, buffer utility has not been experimentally
      validated for most species. To address this gap, we conducted a six-year,
      landscape-scale experiment, testing how buffers of different widths affect the
      demographic structure of two amphibian species at 11 ephemeral pools in a working
      forest of the northeastern U.S. We randomly assigned each pool to one of three
      treatments (i.e., reference, 100m buffer, 30m buffer) and clearcut to create
      buffers. We captured all spotted salamanders and wood frogs breeding in each pool
      and examined the impacts of treatment and hydroperiod on breeding-population
      abundance, sex ratio, and recapture rate. The negative effects of clearcutting
      tended to increase as forest-buffer width decreased and be strongest for
      salamanders and when other stressors were present (e.g., at short-hydroperiod
      pools). Recapture rates were reduced in the 30m, but not 100m, treatment.
      Throughout the experiment for frogs, and during the first year post-cut for
      salamanders, the predicted mean proportion of recaptured adults in the 30m
      treatment was only 62% and 40%, respectively, of that in the reference treatment.
      Frog sex ratio and abundance did not differ across treatments, but salamander sex
      ratios were increasingly male-biased in both cut treatments. By the final year,
      there were on average, only about 40% and 65% as many females predicted in the
      100m and 30m treatments, respectively, compared to the first year. Breeding
      salamanders at short-hydroperiod pools were about 10% as abundant in the 100m
      versus reference treatment. Our study demonstrates that buffers partially
      mitigate the impacts of habitat disturbance on wetland-dependent amphibians, but
      buffer width and hydroperiod critically mediate that process. We provide the
      first experimental evidence showing that 30-m-wide buffers may be insufficient
      for maintaining resilient breeding populations of pool-dependent amphibians, at
      least during the first six years post-disturbance.

PMID- 26196130
TI  - Weight Loss Instead of Weight Gain within the Guidelines in Obese Women during
      Pregnancy: A Systematic Review and Meta-Analyses of Maternal and Infant Outcomes.
AB  - BACKGROUND: Controversy exists about how much, if any, weight obese pregnant
      women should gain. While the revised Institute of Medicine guidelines on
      gestational weight gain (GWG) in 2009 recommended a weight gain of 5-9 kg for
      obese pregnant women, many studies suggested even gestational weight loss (GWL)
      for obese women. OBJECTIVES: A systematic review was conducted to summarize
      pregnancy outcomes in obese women with GWL compared to GWG within the 2009
      Institute of Medicine guidelines (5-9 kg). DESIGN: Five databases were searched
      from 1 January 2009 to 31 July 2014. The Cochrane Handbook for Systematic Reviews
      of Interventions and the PRISMA Statement were followed. A modified version of
      the Newcastle-Ottawa scale was used to assess individual study quality. Small for
      gestational age (SGA), large for gestational age (LGA) and preterm birth were our
      primary outcomes. RESULTS: Six cohort studies were included, none of which
      assessed preterm birth. Compared to GWG within the guidelines, women with GWL had
      higher odds of SGA <10th percentile (adjusted odds ratio [AOR] 1.76; 95%
      confidence interval [CI] 1.45-2.14) and SGA <3rd percentile (AOR 1.62; 95% CI
      1.19-2.20) but lower odds of LGA >90th percentile (AOR 0.57; 95% CI 0.52-0.62).
      There was a trend towards a graded relationship between SGA <10th percentile and
      each of three obesity classes (I: AOR 1.73; 95% CI 1.53-1.97; II: AOR 1.63; 95%
      CI 1.44-1.85 and III: AOR 1.39; 95% CI 1.17-1.66, respectively). CONCLUSION:
      Despite decreased odds of LGA, increased odds of SGA and a lack of information on
      preterm birth indicate that GWL should not be advocated in general for obese
      women.

PMID- 26196131
TI  - Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form
      (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination
      History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.
AB  - In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the
      sharing of needles and equipment among intravenous drug users (IDUs). Over the
      last few decades, many studies have proven time and again that the diversity of
      HIV-1 epidemics can often be linked to the route of infection transmission. That
      said, the diversity and complexity of HIV-1 molecular epidemics in the region
      have been increasing at an alarming rate, due in part to the high tendency of the
      viral RNA to recombine. This scenario was exemplified by the discovery of
      numerous circulating recombinant forms (CRFs), especially in Thailand and
      Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which
      was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia.
      The near-full length genomes were composed of CRF01_AE and subtype B', with eight
      breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared
      four and two recombination hotspots with the previously described CRF33_01B and
      the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic
      analysis of CRF74_01B genomic regions showed that it is closely related to both
      CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a
      direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B'
      that could have emerged in the mid-1990s. Additionally, it illustrated the active
      recombination processes between prevalent HIV-1 subtypes and recombinants in
      Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among
      IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of
      considerable significance towards the understanding of the genetic diversity and
      population dynamics of HIV-1 circulating in the region. 

PMID- 26196132
TI  - A New Method for Estimating the Number of Undiagnosed HIV Infected Based on HIV
      Testing History, with an Application to Men Who Have Sex with Men in Seattle/King
      County, WA.
AB  - We develop a new approach for estimating the undiagnosed fraction of HIV cases,
      the first step in the HIV Care Cascade. The goal is to address a critical
      blindspot in HIV prevention and treatment planning, with an approach that
      simplifies data requirements and can be implemented with open-source software.
      The primary data required is HIV testing history information on newly diagnosed
      cases. Two methods are presented and compared. The first is a general methodology
      based on simplified back-calculation that can be used to assess changes in the
      undiagnosed fraction over time. The second makes an assumption of constant
      incidence, allowing the estimate to be expressed as a simple closed formula
      calculation. We demonstrate the methods with an application to HIV diagnoses
      among men who have sex with men (MSM) from Seattle/King County. The estimates
      suggest that 6% of HIV-infected MSM in King County are undiagnosed, about one
      third of the comparable national estimate. A sensitivity analysis on the key
      distributional assumption gives an upper bound of 11%. The undiagnosed fraction
      varies by race/ethnicity, with estimates of 4.9% among white, 8.6% of African
      American, and 9.3% of Hispanic HIV-infected MSM being undiagnosed. 

PMID- 26196133
TI  - Late Post-Conditioning with Sevoflurane after Cardiac Surgery--Are Surrogate
      Markers Associated with Clinical Outcome?
AB  - INTRODUCTION: In a recent randomized controlled trial our group has demonstrated
      in 102 patients that late post-conditioning with sevoflurane performed in the
      intensive care unit after surgery involving extracorporeal circulation reduced
      damage to cardiomyocytes exposed to ischemia reperfusion injury. On the first
      post-operative day the sevoflurane patients presented with lower troponin T
      values when compared with those undergoing propofol sedation. In order to assess
      possible clinical relevant long-term implications in patients enrolled in this
      study, we performed the current retrospective analysis focusing on cardiac and
      non-cardiac events during the first 6 months after surgery. METHODS: All patients
      who had successfully completed the late post-conditioning trial were included
      into this follow-up. Our primary and secondary endpoints were the proportion of
      patients experiencing cardiac and non-cardiac events, respectively. Additionally,
      we were interested in assessing therapeutic interventions such as initiation or
      change of drug therapy, interventional treatment or surgery. RESULTS: Of 102
      patients analyzed in the primary study 94 could be included in this follow-up. In
      the sevoflurane group (with 41 patients) 16 (39%) experienced one or several
      cardiac events within 6 months after cardiac surgery, in the propofol group (with
      53 patients) 19 (36%, p=0.75). Four patients (9%) with sevoflurane vs. 7 (13%)
      with propofol sedation had non-cardiac events (p=0.61). While a similar
      percentage of patients suffered from cardiac and/or non-cardiac events, only 12
      patients in the sevoflurane group compared to 20 propofol patients needed a
      therapeutic intervention (OR: 0.24, 95% CI: 0.04-1.43, p=0.12). A similar result
      was found for hospital admissions: 2 patients in the sevoflurane group had to be
      re-admitted to the hospital compared to 8 in the propofol group (OR 0.23, 95% CI:
      0.04-1.29, p=0.10). CONCLUSIONS: Sevoflurane does not seem to provide protection
      with regard to the occurrence of cardiac and non-cardiac events in the 6-month
      period following cardiac surgery with the use of extracorporeal circulation.
      However, there was a clear trend towards fewer interventions (less need for
      treatment, fewer hospital admissions) associated with sevoflurane post
      conditioning in patients experiencing any event. Such results might encourage
      launching large multicenter post-conditioning trials with clinical outcome
      defined as primary endpoint.

PMID- 26196134
TI  - Hunting, Food Preparation, and Consumption of Rodents in Lao PDR.
AB  - A cross-sectional study was conducted in 29 villages of Khamkeuth District in
      Bolikhamxay Province in the Lao PDR during March to May 2013. The study aimed to
      determine the characteristics associated with rodent consumption and related
      behaviors among different ethnic groups, ages, and genders. Five-hundred-eighty
      four (584) males and females from 18-50 years of age participated in this study.
      Half of them were Hmong (292, 50%) while 152 respondents were Lao-Tai (26%) or
      other ethnic groups (140, 24%). Most of the respondents (79.5%) had farming as
      their main occupation. Prevalences of the studied outcomes were high: 39.9 for
      hunting or capturing rodents in the previous year, 77.7% for preparing rodents as
      food, and 86.3% for rodent consumption. Multivariable logistic regression
      analysis showed that likelihood of these types of rodent contact was more
      consistently associated with behavioral factors (gathering things from the forest
      and elsewhere, cultivation-related activities, and taking measures to prevent
      rodent-borne disease) than with socio-demographic, environmental, or cultural
      factors. The strongest associations were observed for gathering things; these
      associations were consistently positive and statistically significant. Although
      this study did not directly assess rodent-borne zoonosis risk, we believe that
      study findings raise concern that such risk may be substantial in the study area
      and other similar areas. Further epidemiological studies on the association
      between rodent-borne disease infection and rodent hunting, preparation for food,
      and consumption are recommended. Moreover, further studies are needed on the
      association between these potential exposure factors (i.e., rodent hunting,
      preparation for food, and consumption) and rodent-borne infections, especially
      among ethnic groups like the Hmong in Lao PDR and those in neighboring countries
      with similar socio-demographic, environmental, behavioral and cultural contexts.

PMID- 26196136
TI  - Making amends : Adaptive perspectives on conflict remediation in monkeys, apes,
      and humans.
AB  - Conflict is an integral, and potentially disruptive, element in the lives of
      humans and other group-living animals. But conflicts are often settled, sometimes
      within minutes after the altercation has ended. The goal of this paper is to
      understand why primates, including humans, make amends. Primatologists have
      gathered an impressive body of evidence which demonstrates that monkeys and apes
      use a variety of behavioral mechanisms to resolve conflicts. Peaceful post
      conflict interactions in nonhuman primates, sometimes labeled "reconciliation,"
      have clear and immediate effects upon former adversaries, relieving uncertainty
      about whether aggression will continue, reducing stress, increasing tolerance,
      and reducing anxiety about whether aggressors will resume aggression toward
      former victims. However, the long-term effects of these interactions are less
      clearly established, leaving room to debate the adaptive function of conflict
      resolution strategies among primates. It is possible that reconciliatory behavior
      enhances the quality of valued, long-term social relationships or that
      reconciliatory interactions are signals that the conflict has ended and the
      actor's intentions are now benign. Both of these hypotheses may help us to
      understand how and why monkeys, apes, and humans make amends. 

PMID- 26196137
TI  - Sex differences in children's investment in peers.
AB  - It is hypothesized from within an evolutionary framework that females should be
      less invested in peer relations than males. Investment was operationalized as
      enjoyment in Study 1 and as preference for interaction in Study 2. In the first
      study, four- and six-year-old children's enjoyment of peer interaction was
      observed in 26 groups of same-sex peers. Girls were rated as enjoying their
      interactions significantly less than boys. In the second study, six- and nine
      year-old children were interviewed about the individuals with whom they spend
      time in their homes and neighborhoods and about the individuals who participate
      in their favorite activities. The proportion of individuals named by children who
      were peers was significantly lower for girls than boys both in children's
      neighborhoods and in children's favorite activities. Results strongly support the
      hypothesis that females and males have evolved differential preferences for
      interaction with peers. 

PMID- 26196135
TI  - Superiority of Minimally Invasive Oesophagectomy in Reducing In-Hospital
      Mortality of Patients with Resectable Oesophageal Cancer: A Meta-Analysis.
AB  - BACKGROUND: Compared with open oesophagectomy (OE), minimally invasive
      oesophagectomy (MIO) proves to have benefits in reducing the risk of pulmonary
      complications for patients with resectable oesophageal cancer. However, it is
      unknown whether MIO has superiority in reducing the occurrence of in-hospital
      mortality (IHM). OBJECTIVE: The objective of this meta-analysis was to explore
      the effect of MIO vs. OE on the occurrence of in-hospital mortality (IHM). DATA
      SOURCES: Sources such as Medline (through December 31, 2014), Embase (through
      December 31, 2014), Wiley Online Library (through December 31, 2014), and the
      Cochrane Library (through December 31, 2014) were searched. STUDY SELECTION: Data
      of randomized and non-randomized clinical trials related to MIO versus OE were
      included. INTERVENTIONS: Eligible studies were those that reported patients who
      underwent MIO procedure. The control group included patients undergoing
      conventional OE. STUDY APPRAISAL AND SYNTHESIS METHODS: Fixed or random -effects
      models were used to calculate summary odds ratios (ORs) or relative risks (RRs)
      for quantification of associations. Heterogeneity among studies was evaluated by
      using Cochran's Q and I2 statistics. RESULTS: A total of 48 studies involving
      14,311 cases of resectable oesophageal cancer were included in the meta-analysis.
      Compared to patients undergoing OE, patients undergoing MIO had statistically
      reduced occurrence of IHM (OR=0.69, 95%CI =0.55 -0.86). Patients undergoing MIO
      also had significantly reduced incidence of pulmonary complications (PCs)
      (RR=0.73, 95%CI = 0.63-0.86), pulmonary embolism (PE) (OR=0.71, 95%CI= 0.51-0.99)
      and arrhythmia (OR=0.79, 95%CI = 0.68-0.92). Non-significant reductions were
      observed among the included studies in the occurrence of anastomotic leak (AL)
      (OR=0.93, 95%CI =0.78-1.11), or Gastric Tip Necrosis (GTN) (OR=0.89, 95%CI =0.54
      1.49). LIMITATION: Most of the included studies were non-randomized case-control
      studies, with a diversity of study designs, demographics of participants and
      surgical intervention. CONCLUSIONS: Minimally invasive oesophagectomy (MIO) has
      superiority over open oesophagectomy (OE) in terms of the occurrence of in
      hospital mortality (IHM) and should be the first-choice surgical procedure in
      esophageal surgery.

PMID- 26196138
TI  - Experimental mood manipulation does not induce change in preference for natural
      landscapes.
AB  - According to evolutionary theory, emotions are psychological mechanisms that have
      evolved to enhance fitness in specific situations by motivating appropriate
      (adaptive) behavior. Taking this perspective, a previous study examined the
      relationship between mood and preference for natural environments. It reported
      that participants' anxiety level was associated with a preference for landscapes
      offering what Appleton called "refuge," while participants' anger and
      cheerfulness were both associated with a preference for landscapes offering what
      Appleton called "prospect." We attempted to replicate these results and to
      improve on the study by experimentally manipulating mood. Using a between
      subjects design, 80 participants were instructed to self-induce one of four
      moods: anger, sadness, anxiety, or joy. After the mood induction, they viewed
      fourteen landscape photographs and recorded the seven most preferred. It was
      hypothesized that subjects experiencing anger or joy would prefer landscapes rich
      in "prospect" features, whereas participants experiencing sadness or anxiety
      would prefer landscapes rich in "refuge" features. In contrast to the previous
      study, the predictions were not supported: artificially induced moods may not
      provide ecological validity as a test of the "mood as motivator" model;
      alternatively, the first study may have reported an alpha error. To see whether
      the model has practical value, we recommend a study of landscape preference using
      participants with clinically significant levels of mood dysphoria. 

PMID- 26196139
TI  - Lineage interests and nonreproductive strategies : An evolutionary approach to
      medieval religious women.
AB  - The nonreproductive role of religious women in the European Middle Ages presents
      the ideal forum for the discussion of elite family strategies within a historical
      context. I apply the evolutionary concept of kin selection to this group of women
      in order to explain how a social formation in which religious women failed to
      reproduce benefited medieval noble lineages. After a brief review of the roles of
      noble women in the later Middle Ages, I identify two benefits that
      nonreproductive women provided within a patrilineal inheritance system. First,
      spatial segregation and Christian ideology together served to curtail the
      production of offspring who could pose a threat to lineage interests. Second,
      cloistered noble women served as a strong political and economic bloc that could
      further lineage interests within a religious context. Finally, I discuss the
      evolutionary basis for the formation of groups of nonreproductive women. Using
      the foundation provided by animal behavioral studies, I apply the twin concepts
      of cooperative breeding and parental manipulation to noble lineages of the
      medieval period. 

PMID- 26196140
TI  - Demographic contexts and the adaptive role of mother-infant attachment : A
      hypothesis.
AB  - Currently much debate surrounds the significance of cross-cultural variation in
      mother-infant attachment. Is only one form of attachment "healthy," or are
      different types of attachment adaptations to local socioecological conditions?
      Juvenile mortality rates have been promoted as important features of local
      environments that shape attachment, which in turn affects later reproductive
      strategies. To this we add fertility. Fertility changes the environment of a
      child by influencing the number of potential caregivers and competitors for care,
      and the cultural ethos regarding the rights of children. Different combinations
      of fertility and mortality will likely give rise to different attachment forms,
      and only under one regime (low fertility and mortality) do we expect exclusivity
      in attachment. 

PMID- 26196141
TI  - The evolutionary context of postnatal depression.
AB  - "Postnatal depression" denotes the syndrome of dysphoria, debility, and anxiety
      that follows childbirth in about 10-20% of women (as variously estimated). Its
      etiology is seen to be lodged in a variety of psychosocial as well as biological
      factors, among which the isolating and pressured culture of contemporary society
      (especially for women/mothers) is commonly singled out as a powerful
      precipitator. This view is extended here through the evolutionary perspective
      which casts maternal distress as a set of adaptive responses with the function,
      in ancestral environments, of soliciting support for a mother who feels that her
      maternal responsiveness may be threatened. As continuous caretaking of the infant
      is the active expression of evolved maternal responsiveness, departures from this
      pattern result in anxiety and distress that seek resolution. Manifestations of
      maternal distress in contemporary society are dysfunctional, however, since the
      present social structure does not provide spontaneous and immediate support that
      can spring forth within small, closely knit social units. Furthermore, for
      present-day mothers distress is self-perpetuating since the ingrained tendency
      toward continuing responsiveness rarely finds practical expression and is thus
      converted into anxious vigilance and depression. This view generates the
      hypothesis that the emotional and cognitive contents of maternal vigilance are
      associated with the needs of the infant and will therefore be focused on crying
      and feeding. A number of qualitative studies of women's experiences during the
      postpartum bear out this prediction and support the feasibility of the
      evolutionary hypothesis of "postnatal depression" as a set of adaptive responses,
      now out of place in a novel environment. 

PMID- 26196142
TI  - On the impact of sex and birth order on contact with kin.
AB  - Previous research indicates that birth order is a strong predictor of familial
      sentiments, with middleborns less family-oriented than first- or last-borns. In
      this research, effects of sex and birth order on the actual frequency of contact
      with maternal and paternal kin were examined in two studies. In Study 1, one
      hundred and forty undergraduates completed a questionnaire relating to the amount
      of time they spent in contact with specific relatives, while in Study 2, one
      hundred and twelve undergraduates completed the same questionnaire with the
      addition of two questions relating to the subjects' parents' birth orders.
      Subjects were more likely to have frequent contact with maternal, as opposed to
      paternal, kin and women experienced more frequent contact than men with relatives
      in general. The birth order of subjects did not appear to have a significant
      influence on contact but the birth order of the subjects' parents did, with the
      offspring of middleborn mothers having relatively little contact with maternal
      grandparents and the offspring of middleborn fathers having relatively little
      contact with paternal grandparents. These sex and birth order differences are
      discussed in relation to possible differences in how women and men use kinship
      ties and in terms of how birth order may influence parental solicitude. 

PMID- 26196143
TI  - Packer and colleagues' model of menopause for humans.

PMID- 26196145
TI  - The active-zone protein Munc13 controls the use-dependence of presynaptic voltage
      gated calcium channels.
AB  - Presynaptic calcium channel function is critical for converting electrical
      information into chemical communication but the molecules in the active zone that
      sculpt this function are poorly understood. We show that Munc13, an active-zone
      protein essential for exocytosis, also controls presynaptic voltage-gated calcium
      channel (VGCC) function dictating their behavior during various forms of
      activity. We demonstrate that in vitro Munc13 interacts with voltage-VGCCs via a
      pair of basic residues in Munc13's C2B domain. We show that elimination of this
      interaction by either removal of Munc13 or replacement of Munc13 with a Munc13
      C2B mutant alters synaptic VGCC's response to and recovery from high-frequency
      action potential bursts and alters calcium influx from single action potential
      stimuli. These studies illustrate a novel form of synaptic modulation and show
      that Munc13 is poised to profoundly impact information transfer at nerve
      terminals by controlling both vesicle priming and the trigger for exocytosis. 

PMID- 26196144
TI  - Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence.
AB  - In Caenorhabditis elegans, ablation of germline stem cells (GSCs) extends
      lifespan, but also increases fat accumulation and alters lipid metabolism,
      raising the intriguing question of how these effects might be related. Here, we
      show that a lack of GSCs results in a broad transcriptional reprogramming in
      which the conserved detoxification regulator SKN-1/Nrf increases stress
      resistance, proteasome activity, and longevity. SKN-1 also activates diverse
      lipid metabolism genes and reduces fat storage, thereby alleviating the increased
      fat accumulation caused by GSC absence. Surprisingly, SKN-1 is activated by
      signals from this fat, which appears to derive from unconsumed yolk that was
      produced for reproduction. We conclude that SKN-1 plays a direct role in
      maintaining lipid homeostasis in which it is activated by lipids. This SKN-1
      function may explain the importance of mammalian Nrf proteins in fatty liver
      disease and suggest that particular endogenous or dietary lipids might promote
      health through SKN-1/Nrf. 

PMID- 26196146
TI  - Stress induced gene expression drives transient DNA methylation changes at
      adjacent repetitive elements.
AB  - Cytosine DNA methylation (mC) is a genome modification that can regulate the
      expression of coding and non-coding genetic elements. However, little is known
      about the involvement of mC in response to environmental cues. Using whole genome
      bisulfite sequencing to assess the spatio-temporal dynamics of mC in rice grown
      under phosphate starvation and recovery conditions, we identified widespread
      phosphate starvation-induced changes in mC, preferentially localized in
      transposable elements (TEs) close to highly induced genes. These changes in mC
      occurred after changes in nearby gene transcription, were mostly DCL3a
      independent, and could partially be propagated through mitosis, however no
      evidence of meiotic transmission was observed. Similar analyses performed in
      Arabidopsis revealed a very limited effect of phosphate starvation on mC,
      suggesting a species-specific mechanism. Overall, this suggests that TEs in
      proximity to environmentally induced genes are silenced via hypermethylation, and
      establishes the temporal hierarchy of transcriptional and epigenomic changes in
      response to stress. 

PMID- 26196149
TI  - Correction: "Just Another Tool for Online Studies" (JATOS): An Easy Solution for
      Setup and Management of Web Servers Supporting Online Studies.

PMID- 26196148
TI  - Moderate Perinatal Choline Deficiency Elicits Altered Physiology and Metabolomic
      Profiles in the Piglet.
AB  - Few studies have evaluated the impact of dietary choline on the health and well
      being of swine, and those pivotal papers were aimed at determining dietary
      requirements for sows and growing pigs. This is of importance as the piglet is
      becoming a widely accepted model for human infant nutrition, but little is known
      about the impacts of perinatal choline status on overall health and metabolism of
      the growing piglet. In the present study, sows were provided either a choline
      deficient (CD, 625 mg choline/kg dry matter) or choline sufficient (CS, 1306 mg
      choline/kg dry matter) diet for the last 65 d of gestation (prenatal
      intervention). Piglets were weaned from the sow 48 h after farrowing and provided
      either a CD (477 mg choline/kg dry matter) or CS (1528 mg choline/kg dry matter)
      milk replacer (postnatal intervention) for 29 +/- 2 d, resulting in a factorial
      arrangement of 4 treatment (prenatal/postnatal) groups: CS/CS, CS/CD, CD/CS, and
      CD/CD. Piglet growth was normal for artificially-reared piglets, and was not
      impacted by perinatal choline status. Piglets receiving the postnatal CD
      treatment had lower (P < 0.01) plasma choline and choline-containing phospholipid
      concentrations and higher (P < 0.05) liver enzyme (alkaline phosphatase and gamma
      glutamyl transferase) values compared with piglets receiving the postnatal CS
      treatment. Hepatic lipid content of piglets receiving the postnatal CD treatment
      was higher (P < 0.01) compared with piglets receiving the postnatal CS treatment.
      Additionally, postnatally CD piglets had lower (P = 0.01) plasma cholesterol than
      postnatally CS piglets. Brain development was also impacted by perinatal choline
      status, with brains of piglets exposed to prenatal CD being smaller (P = 0.01)
      than those of prenatally CS piglets. These findings support the hypothesis that
      the piglet is a sensitive model for choline deficiency during the perinatal
      period. In the present study, piglets exhibited similarities in health markers
      and metabolomic profiles to rodents and humans when exposed to moderate choline
      deficiency.

PMID- 26196147
TI  - Effect of Carbohydrate Supplementation on Investment into Offspring Number, Size,
      and Condition in a Social Insect.
AB  - Resource availability can determine an organism's investment strategies for
      growth and reproduction. When nutrients are limited, there are potential
      tradeoffs between investing into offspring number versus individual offspring
      size. In social insects, colony investment in offspring size and number may shift
      in response to colony needs and the availability of food resources. We
      experimentally manipulated the diet of a polymorphic ant species (Solenopsis
      invicta) to test how access to the carbohydrate and amino acid components of
      nectar resources affect colony investment in worker number, body size, size
      distributions, and individual percent fat mass. We reared field-collected
      colonies on one of four macronutrient treatment supplements: water, amino acids,
      carbohydrates, and amino acid and carbohydrates. Having access to carbohydrates
      nearly doubled colony biomass after 60 days. This increase in biomass resulted
      from an increase in worker number and mean worker size. Access to carbohydrates
      also altered worker body size distributions. Finally, we found a negative
      relationship between worker number and size, suggesting a tradeoff in colony
      investment strategies. This tradeoff was more pronounced for colonies without
      access to carbohydrate resources. The monopolization of plant-based resources has
      been implicated in the ecological success of ants. Our results shed light on a
      possible mechanism for this success, and also have implications for the success
      of introduced species. In addition to increases in colony size, our results
      suggest that having access to plant-based carbohydrates can also result in larger
      workers that may have better individual fighting ability, and that can withstand
      greater temperature fluctuations and periods of food deprivation. 

PMID- 26196150
TI  - Profiling Aglycon-Recognizing Sites of UDP-glucose:glycoprotein
      Glucosyltransferase by Means of Squarate-Mediated Labeling.
AB  - Because of its ability to selectively glucosylate misfolded glycoproteins, UDP
      glucose:glycoprotein glucosyltransferase (UGGT) functions as a folding sensor in
      the glycoprotein quality control system in the endoplasmic reticulum (ER). The
      unique property of UGGT derives from its ability to transfer a glucose residue to
      N-glycan moieties of incompletely folded glycoproteins. We have previously
      discovered nonproteinic synthetic substrates of this enzyme, allowing us to
      conduct its high-sensitivity assay in a quantitative manner. In this study, we
      aimed to conduct site-selective affinity labeling of UGGT using a functionalized
      oligosaccharide probe to identify domain(s) responsible for recognition of the
      aglycon moiety of substrates. To this end, a probe 1 was designed to selectively
      label nucleophilic amino acid residues in the proximity of the canonical aglycon
      recognizing site of human UGGT1 (HUGT1) via squaramide formation. As expected,
      probe 1 was able to label HUGT1 in the presence of UDP. Analysis by nano-LC
      ESI/MS(n) identified a unique lysine residue (K1424) that was modified by 1. Kyte
      Doolittle analysis as well as homology modeling revealed a cluster of hydrophobic
      amino acids that may be functional in the folding sensing mechanism of HUGT1.

PMID- 26196152
TI  - Time to make the change from 'primary biliary cirrhosis' to 'primary biliary
      cholangitis'.

PMID- 26196151
TI  - Glitazone Treatment and Incidence of Parkinson's Disease among People with
      Diabetes: A Retrospective Cohort Study.
AB  - BACKGROUND: Recent in vitro and animal experiments suggest that peroxisome
      proliferation-activated receptor gamma (PPARgamma) agonist medications, such as
      antidiabetic glitazone (GTZ) drugs, are neuroprotective in models of Parkinson's
      disease (PD). These findings have not been tested in humans. We hypothesized that
      individuals prescribed GTZ drugs would have a lower incidence of PD compared to
      individuals prescribed other treatments for diabetes. METHODS AND FINDINGS: Using
      primary care data from the United Kingdom Clinical Practice Research Datalink
      (CPRD), we conducted a retrospective cohort study in which individuals with
      diabetes who were newly prescribed GTZ (GTZ-exposed group) were matched by age,
      sex, practice, and diabetes treatment stage with up to five individuals
      prescribed other diabetes treatments (other antidiabetic drug-exposed group).
      Patients were followed up from 1999 until the first recording of a PD diagnosis,
      end of observation in the database, or end of the study (1 August 2013). An
      incidence rate ratio (IRR) was calculated using conditional Poisson regression,
      adjusted for possible confounders. 44,597 GTZ exposed individuals were matched to
      120,373 other antidiabetic users. 175 GTZ-exposed individuals were diagnosed with
      PD compared to 517 individuals in the other antidiabetic drug-exposed group. The
      incidence rate (IR) of PD in the GTZ-exposed group was 6.4 per 10,000 patient
      years compared with 8.8 per 10,000 patient years in those prescribed other
      antidiabetic treatments (IRR 0.72, 95% confidence interval [CI] 0.60-0.87).
      Adjustments for potential confounding variables, including smoking, other
      medications, head injury, and disease severity, had no material impact (fully
      adjusted IRR 0.75, 0.59-0.94). The risk was reduced in those with current GTZ
      prescriptions (current GTZ-exposed IRR 0.59, 0.46-0.77) but not reduced among
      those with past prescriptions (past GTZ-exposed IRR 0.85, 0.65-1.10). Our study
      only included patients with diabetes who did not have a PD diagnosis when they
      were first prescribed GTZ, and thus, it cannot establish whether GTZ use prevents
      or slows the progression of PD. CONCLUSIONS: In patients with diabetes, a current
      prescription for GTZ is associated with a reduction in incidence of PD. This
      suggests PPAR gamma pathways may be a fruitful drug target in PD.

PMID- 26196153
TI  - Smallpox Vaccination of Laboratory Workers at US Variola Testing Sites.
AB  - To evaluate the need to revaccinate laboratory workers against smallpox, we
      assessed regular revaccination at the US Laboratory Response Network's variola
      testing sites by examining barriers to revaccination and the potential for
      persistence of immunity. Our data do not provide evidence to suggest prolonging
      the recommended interval for revaccination. 

PMID- 26196154
TI  - Biofuels via Fast Pyrolysis of Perennial Grasses: A Life Cycle Evaluation of
      Energy Consumption and Greenhouse Gas Emissions.
AB  - A well-to-wheel (WTW) life cycle assessment (LCA) model is developed to evaluate
      the environmental profile of producing liquid transportation fuels via fast
      pyrolysis of perennial grasses: switchgrass and miscanthus. The framework
      established in this study consists of (1) an agricultural model used to determine
      biomass growth rates, agrochemical application rates, and other key parameters in
      the production of miscanthus and switchgrass biofeedstock; (2) an ASPEN model
      utilized to simulate thermochemical conversion via fast pyrolysis and catalytic
      upgrading of bio-oil to renewable transportation fuel. Monte Carlo analysis is
      performed to determine statistical bounds for key sustainability and performance
      measures including life cycle greenhouse gas (GHG) emissions and Energy Return on
      Investment (EROI). The results of this work reveal that the EROI and GHG
      emissions (gCO2e/MJ-fuel) for fast pyrolysis derived fuels range from 1.52 to
      2.56 and 22.5 to 61.0 respectively, over the host of scenarios evaluated. Further
      analysis reveals that the energetic performance and GHG reduction potential of
      fast pyrolysis-derived fuels are highly sensitive to the choice of coproduct
      scenario and LCA allocation scheme, and in select cases can change the life cycle
      carbon balance from meeting to exceeding the renewable fuel standard emissions
      reduction threshold for cellulosic biofuels.

PMID- 26196155
TI  - Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by
      Transverse Aortic Constriction in Mice.
AB  - BACKGROUND: Uncoupling protein 2 (UCP2) is critical in regulating energy
      metabolism. Due to the significant change in energy metabolism of myocardium upon
      pressure overload, we hypothesize that UCP2 could contribute to the etiology of
      cardiac hypertrophy. METHODS: Adult male C57BL/6J mice were subjected to pressure
      overload by using transverse aortic constriction (TAC), and then received genipin
      (a UCP2 selective inhibitor; 25 mg/kg/d, ip) or vehicle for three weeks prior to
      histologic assessment of myocardial hypertrophy. ATP concentration, ROS level,
      and myocardial apoptosis were also examined. A parallel set of experiments was
      also conducted in UCP2-/- mice. RESULTS: TAC induced left ventricular
      hypertrophy, as reflected by increased ventricular weight/thickness and increased
      size of myocardial cell (vs. sham controls). ATP concentration was decreased; ROS
      level was increased. Apoptosis and fibrosis markers were increased. TAC increased
      mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels.
      Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical
      changes described above. Hypertrophy and associated changes induced by TAC in
      UCP2-/- mice were much less pronounced than in WT mice. CONCLUSIONS: Blocking
      UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

PMID- 26196156
TI  - Rhodium-Catalyzed Cyanation of C(sp(2))-H Bond of Alkenes.
AB  - Efficient and selective rhodium-catalyzed cyanation of chelation-assisted C-H
      bonds of alkenes has been accomplished using environmentally benign N-cyano-N
      phenyl-p-methylbenzenesulfonamide (NCTS) as a cyanating reagent. The developed
      methodology tolerates various functional groups and allows the synthesis of
      diverse substituted acrylonitriles in good to excellent yields. Furthermore, the
      potential of the methodology was demonstrated through the formal synthesis of
      chlorpheniramine-based antagonist. 

PMID- 26196157
TI  - Direct, Robust Technique for the Measurement of Friction between Microspheres.
AB  - Friction between microscopic objects controls many macroscopic phenomena. For
      instance, the friction between microasperities determines the tribology of rough
      surfaces in contact and in relative motion. Additionally, the friction between
      microparticles is responsible for many aspects of the rheological response of
      granular media, ranging from microscale contacts at the single-particle level to
      macroscopic flow properties of sheared, dry granular systems and non-Brownian
      suspensions. We propose a new, precise, and robust method, based on lateral force
      microscopy, to measure the coefficient of friction between microspheres
      quantitatively and without complex data processing. We have successfully applied
      this method to the contact between silica spheres in liquid with and without a
      polymer coating. 

PMID- 26196158
TI  - Risk for Mycobacterial Disease among Patients with Rheumatoid Arthritis, Taiwan,
      2001-2011.
AB  - Increasing evidence indicates that the risk of acquiring tuberculosis (TB) and
      nontuberculous mycobacterial disease is elevated among patients with rheumatoid
      arthritis (RA). To determine the epidemiology of mycobacterial diseases among RA
      patients in Asia, we conducted a retrospective cohort study. We used a nationwide
      database to investigate the association of RA with mycobacterial diseases. The
      risk for development of TB or nontuberculous mycobacterial disease was 2.28-fold
      and 6.24-fold higher among RA patients than among the general population,
      respectively. Among RA patients, risk for development of mycobacterial disease
      was higher among those who were older, male, or both. Furthermore, among RA
      patients with mycobacterial infections, the risk for death was increased.
      Therefore, RA patients, especially those with other risk factors, should be
      closely monitored for development of mycobacterial disease. 

PMID- 26196159
TI  - Trends in Syntheses, Structures, and Properties for Three Series of Ammine Rare
      Earth Metal Borohydrides, M(BH4)3.nNH3 (M = Y, Gd, and Dy).
AB  - Fourteen solvent- and halide-free ammine rare-earth metal borohydrides
      M(BH4)3.nNH3, M = Y, Gd, Dy, n = 7, 6, 5, 4, 2, and 1, have been synthesized by a
      new approach, and their structures as well as chemical and physical properties
      are characterized. Extensive series of coordination complexes with systematic
      variation in the number of ligands are presented, as prepared by combined
      mechanochemistry, solvent-based methods, solid-gas reactions, and thermal
      treatment. This new synthesis approach may have a significant impact within
      inorganic coordination chemistry. Halide-free metal borohydrides have been
      synthesized by solvent-based metathesis reactions of LiBH4 and MCl3 (3:1),
      followed by reactions of M(BH4)3 with an excess of NH3 gas, yielding M(BH4)3.7NH3
      (M = Y, Gd, and Dy). Crystal structure models for M(BH4)3.nNH3 are derived from a
      combination of powder X-ray diffraction (PXD), (11)B magic-angle spinning NMR,
      and density functional theory (DFT) calculations. The structures vary from two
      dimensional layers (n = 1), one-dimensional chains (n = 2), molecular compounds
      (n = 4 and 5), to contain complex ions (n = 6 and 7). NH3 coordinates to the
      metal in all compounds, while BH4(-) has a flexible coordination, i.e., either as
      a terminal or bridging ligand or as a counterion. M(BH4)3.7NH3 releases ammonia
      stepwise by thermal treatment producing M(BH4)3.nNH3 (6, 5, and 4), whereas
      hydrogen is released for n <= 4. Detailed analysis of the dihydrogen bonds
      reveals new insight about the hydrogen elimination mechanism, which contradicts
      current hypotheses. Overall, the present work provides new general knowledge
      toward rational materials design and preparation along with limitations of PXD
      and DFT for analysis of structures with a significant degree of dynamics in the
      structures. 

PMID- 26196160
TI  - Intrinsically Mn2+-Chelated Polydopamine Nanoparticles for Simultaneous Magnetic
      Resonance Imaging and Photothermal Ablation of Cancer Cells.
AB  - Theranostic agents for magnetic resonance imaging (MRI) guided photothermal
      therapy have attracted intensive interest in cancer diagnosis and treatment.
      However, the development of biocompatible theranostic agents with high
      photothermal conversion efficiency and good MRI contrast effect remains a
      challenge. Herein, PEGylated Mn2+-chelated polydopamine (PMPDA) nanoparticles
      were successfully developed as novel theranostic agents for simultaneous MRI
      signal enhancement and photothermal ablation of cancer cells, based on intrinsic
      manganese-chelating properties and strong near-infrared absorption of
      polydopamine nanomaterials. The obtained PMPDA nanoparticles showed significant
      MRI signal enhancement for both in vitro and in vivo imaging. Highly effective
      photothermal ablation of HeLa cells exposed to PMPDA nanoparticles was then
      achieved upon laser irradiation for 10 min. Furthermore, the excellent
      biocompatibility of PMPDA nanoparticles, because of the use of Mn2+ ions as
      diagnostic agents and biocompatible polydopamine as photothermal agents, was
      confirmed by a standard MTT assay. Therefore, the developed PMPDA nanoparticles
      could be used as a promising theranostic agent for MRI-guided photothermal
      therapy of cancer cells.

PMID- 26196161
TI  - Glucosinolate Diversity in Bretschneidera sinensis of Chinese Origin.
AB  - The glucosinolate (GL) profile in several plant parts (leaf, branch, bark, root,
      and fruit) of Bretschneidera sinensis from three geographical regions of the
      People's Republic of China was established for the first time by HPLC. During
      this investigation, benzyl GL (1), 4-hydroxybenzyl GL (2), 2-hydroxy-2
      methylpropyl GL (3), and 4-methoxybenzyl GL (4) were identified. In addition, one
      new GL, 3-hydroxy-4-methoxybenzyl GL (5), was isolated in a minor amount from the
      fruit and characterized by spectroscopic data interpretation. Furthermore, traces
      of 4-hydroxy-3-methoxyphenylacetonitrile were detected by GC-MS analysis in the
      fruits, thus confirming the presence of the regioisomeric 4-hydroxy-3
      methoxybenzyl GL (6). GLs 1-5 were also quantified for the first time by HPLC in
      the various plant organs. 

PMID- 26196162
TI  - Two-Photon Absorption in Organometallic Bromide Perovskites.
AB  - Organometallic trihalide perovskites are solution-processed semiconductors that
      have made great strides in third-generation thin film light-harvesting and light
      emitting optoelectronic devices. Recently, it has been demonstrated that large,
      high-purity single crystals of these perovskites can be synthesized from the
      solution phase. These crystals' large dimensions, clean bandgap, and solid-state
      order have provided us with a suitable medium to observe and quantify two-photon
      absorption in perovskites. When CH3NH3PbBr3 single crystals are pumped with
      intense 800 nm light, we observe band-to-band photoluminescence at 572 nm,
      indicative of two-photon absorption. We report the nonlinear absorption
      coefficient of CH3NH3PbBr3 perovskites to be 8.6 cm GW(-1) at 800 nm, comparable
      to epitaxial single-crystal semiconductors of similar bandgap. We have leveraged
      this nonlinear process to electrically autocorrelate a 100 fs pulsed laser using
      a two-photon perovskite photodetector. This work demonstrates the viability of
      organometallic trihalide perovskites as a convenient and low-cost nonlinear
      absorber for applications in ultrafast photonics. 

PMID- 26196163
TI  - Tailoring the Electrical Properties of HfO2 MOS-Devices by Aluminum Doping.
AB  - In this work dielectric and electrical properties of Al-doped HfO2 layers
      deposited by plasma-enhanced atomic layer deposition in dependence on the
      thickness and the added Al amount in the films have been investigated. Special
      attention is dedicated to C-V and I-V hysteresis analysis as a measure for
      trapping phenomena in the films. A detailed study of conduction mechanisms in
      dependence on the composition of the layers has also been performed. The
      densities and spatial and energy positions of traps have been examined. It is
      found that only a small amount of Al-doping decreases the trapping which is
      assigned to a reduction of oxygen vacancy-related traps in HfO2. On the contrary,
      higher amounts of Al introduced in HfO2 films increase the trapping ability of
      the stacks which is due to the introduction of deeper Al2O3-related traps. The
      results imply that by adding a proper amount of Al into HfO2 it is possible to
      tailor dielectric and electrical properties of high-k layers toward meeting the
      criteria for particular applications. 

PMID- 26196164
TI  - The Depths of Hydraulic Fracturing and Accompanying Water Use Across the United
      States.
AB  - Reports highlight the safety of hydraulic fracturing for drinking water if it
      occurs "many hundreds of meters to kilometers underground". To our knowledge,
      however, no comprehensive analysis of hydraulic fracturing depths exists. Based
      on fracturing depths and water use for ~44,000 wells reported between 2010 and
      2013, the average fracturing depth across the United States was 8300 ft (~2500
      m). Many wells (6900; 16%) were fractured less than a mile from the surface, and
      2600 wells (6%) were fractured above 3000 ft (900 m), particularly in Texas (850
      wells), California (720), Arkansas (310), and Wyoming (300). Average water use
      per well nationally was 2,400,000 gallons (9,200,000 L), led by Arkansas
      (5,200,000 gallons), Louisiana (5,100,000 gallons), West Virginia (5,000,000
      gallons), and Pennsylvania (4,500,000 gallons). Two thousand wells (~5%)
      shallower than one mile and 350 wells (~1%) shallower than 3000 ft were
      hydraulically fractured with >1 million gallons of water, particularly in
      Arkansas, New Mexico, Texas, Pennsylvania, and California. Because hydraulic
      fractures can propagate 2000 ft upward, shallow wells may warrant special
      safeguards, including a mandatory registry of locations, full chemical
      disclosure, and, where horizontal drilling is used, predrilling water testing to
      a radius 1000 ft beyond the greatest lateral extent.

PMID- 26196165
TI  - Real-Time Microbiology Laboratory Surveillance System to Detect Abnormal Events
      and Emerging Infections, Marseille, France.
AB  - Infectious diseases are a major threat to humanity, and accurate surveillance is
      essential. We describe how to implement a laboratory data-based surveillance
      system in a clinical microbiology laboratory. Two historical Microsoft Excel
      databases were implemented. The data were then sorted and used to execute the
      following 2 surveillance systems in Excel: the Bacterial real-time Laboratory
      based Surveillance System (BALYSES) for monitoring the number of patients
      infected with bacterial species isolated at least once in our laboratory during
      the study periodl and the Marseille Antibiotic Resistance Surveillance System
      (MARSS), which surveys the primary beta-lactam resistance phenotypes for 15
      selected bacterial species. The first historical database contained 174,853
      identifications of bacteria, and the second contained 12,062 results of
      antibiotic susceptibility testing. From May 21, 2013, through June 4, 2014,
      BALYSES and MARSS enabled the detection of 52 abnormal events for 24 bacterial
      species, leading to 19 official reports. This system is currently being refined
      and improved. 

PMID- 26196166
TI  - Yoga as a Therapeutic Intervention: A Bibliometric Analysis of Published Research
      Studies from 1967 to 2013.
AB  - OBJECTIVE: A comprehensive bibliometric analysis was conducted on publications
      for yoga therapy research in clinical populations. METHODS: Major electronic
      databases were searched for articles in all languages published between 1967 and
      2013. Databases included PubMed, PsychInfo, MEDLINE, IndMed, Indian Citation
      Index, Index Medicus for South-East Asia Region, Web of Knowledge, Embase, EBSCO,
      and Google Scholar. Nonindexed journals were searched manually. Key search words
      included yoga, yoga therapy, pranayama, asana. All studies met the definition of
      a clinical trial. All styles of yoga were included. The authors extracted the
      data. RESULTS: A total of 486 articles met the inclusion criteria and were
      published in 217 different peer-reviewed journals from 29 different countries on
      28,080 study participants. The primary result observed is the three-fold increase
      in number of publications seen in the last 10 years, inclusive of all study
      designs. Overall, 45% of the studies published were randomized controlled trials,
      18% were controlled studies, and 37% were uncontrolled studies. Most publications
      originated from India (n=258), followed by the United States (n=122) and Canada
      (n=13). The top three disorders addressed by yoga interventions were mental
      health, cardiovascular disease, and respiratory disease. CONCLUSION: A surge in
      publications on yoga to mitigate disease-related symptoms in clinical populations
      has occurred despite challenges facing the field of yoga research, which include
      standardization and limitations in funding, time, and resources. The population
      at large has observed a parallel surge in the use of yoga outside of clinical
      practice. The use of yoga as a complementary therapy in clinical practice may
      lead to health benefits beyond traditional treatment alone; however, to effect
      changes in health care policy, more high-quality, evidence-based research is
      needed.

PMID- 26196167
TI  - Cardiac autonomic dysfunction in elderly women with myocardial infarction.
AB  - AIMS: Elderly women with myocardial infarction (MI) show poorer outcomes than
      men. In patients with MI, reduced heart rate variability (HRV) is associated with
      an increased risk of mortality. Thus, we aimed to investigate HRV in elderly
      women with MI. METHODS: HRV indexes in women 50 years of age or older were
      compared to those in age-adjusted men with MI: geometric (triangular index),
      linear (low frequency [LF, ms(2)], high frequency [HF, ms(2)], standard deviation
      (SD) of normal R-R wave intervals [SDNN], square root of the mean of the sum of
      the squares of differences between adjacent normal R wave intervals [RMSSD]) and
      nonlinear Poincare analysis [SD1 and SD2, ms]. RESULTS: Women had higher MI
      recurrence than men (11% vs. 5% with two MIs; 6% vs. 1% with three MIs). Overall
      HRV, the triangular index and SDNN were considerably lower in women than men (3.1
      [2.5-4.4] vs. 4.5 [3.2-5.9] and 9.3 [6.9-15.8] vs. 19.2 [11.4-26.4] respectively;
      p < 0.001). Moreover, HRV indexes (HF, LF/HF, RMSSD, and SD1) were significantly
      lower in women (62.2%, 55.6%, 37.1%, and 37.2% respectively; p < 0.01).
      CONCLUSION: This study suggests that elderly women with MI may have a worse
      prognosis than men, indicated by cardiac autonomic dysfunction. Since our study
      is cross-sectional and cannot infer causality, causation should be confirmed in
      further longitudinal studies.

PMID- 26196168
TI  - Intermethod reliability and factors affecting recall with the Temple University
      Community Participation measure.
AB  - BACKGROUND: Increased interest in promoting community inclusion of adults with
      serious mental illnesses will necessitate advances in measuring community
      participation as an outcome of such efforts. AIMS: The primary aim of this study
      is to examine the intermethod reliability of the Temple University Community
      Participation (TUCP) measure with a daily checklist approach. Secondary aims are
      to explore the influence of frequency and importance of participation on recall
      consistency. METHOD: One hundred and seven individuals diagnosed with a
      schizophrenia-spectrum disorder, bipolar disorder, or major depression completed
      a daily checklist of community participation in 25 areas. Approximately 30 days
      later they completed the TUCP measure involving recall of participation in these
      same areas. RESULTS: TUCP responses were highly correlated with totals from the
      daily checklists. Participation areas with more participation days have higher
      TUCP-diary checklist correlations. Importance of the participation area did not
      appear to affect correlations. CONCLUSIONS: The TUCP is a usable and relatively
      unobtrusive measure of community participation. Modest evidence found that more
      frequent events were recalled more consistently.

PMID- 26196169
TI  - Music therapy as a non-pharmacological treatment for epilepsy.
AB  - Epilepsy is one of the most common neurological diseases. Currently, the primary
      methods of treatment include pharmacological and surgical treatment. However,
      approximately one-third of patients exhibit refractory epilepsy. Therefore, a
      novel approach to epilepsy treatment is necessary. Several studies have confirmed
      that music therapy can be effective at reducing seizures and epileptiform
      discharges, thus providing a new option for clinicians in the treatment of
      epilepsy. Although the underlying mechanism of music therapy is unknown, it may
      be related to resonance, mirror neurons, dopamine pathways and parasympathetic
      activation. Large sample, multicenter, randomized double-blind and more
      effectively designed studies are needed for future music therapy studies. 

PMID- 26196170
TI  - Talk to Me, Please!: The Importance of Qualitative Research to Games for Health.

PMID- 26196172
TI  - Effects of Active Videogames on Physical Activity and Related Outcomes Among
      Healthy Children: A Systematic Review.
AB  - OBJECTIVE: This review systematically evaluated the effects of active videogames
      (AVGs) on physical activity (PA) and related outcomes in healthy children.
      MATERIALS AND METHODS: Electronic databases were searched to retrieve articles
      published from January 2000 through August 2013. Included were original studies
      published in English, in peer-reviewed journals, that included at least one
      subgroup of healthy participants not older than 18 years, and that measured at
      least one PA-related cognitive, psychosocial, or behavioral outcome. All study
      designs were included, but only intervention studies with PA comparison between
      groups or across time were assessed for methodological quality. Evidence strength
      for intervention studies was stratified by settings (including the free-living
      home setting, the school, community, or primary care setting with structured AVG
      sessions [i.e., AVG play of participants was organized by teachers or
      researchers], and multiple settings). RESULTS: Fifty-four articles were
      identified, including 32 studies that examined the immediate PA effects (i.e.,
      energy expenditure and PA levels during AVG play), one survey study, and 21
      intervention studies aimed to promote PA. AVGs led to light- to moderate
      intensity PA among studies of immediate PA outcomes. No effect was identified of
      AVGs on PA in the home setting. Moderate evidence was found that structured AVG
      play could improve PA. Inconclusive evidence was found for the effect of AVGs on
      PA in multiple settings. CONCLUSIONS: The present review does not support using
      AVGs alone in the home setting to promote PA. Structured AVG play has the
      potential to promote PA in children.

PMID- 26196173
TI  - Promoting Children's Health with Digital Games: A Review of Reviews.
AB  - Effective, evidence-based, and interesting methods are needed for children's
      health promotion. Digital games can be such a method, but there is need for a
      summary of the evidence on the effectiveness of digital games in promoting
      children's health. The aim of this review of reviews was to evaluate the quality
      of systematic reviews, to summarize the evidence in systematic reviews and
      reviews related to the effectiveness of digital games in children's health
      promotion, and to identify gaps in knowledge. A systematic literature search was
      conducted in May-August 2013 from relevant databases, and 1178 references were
      found. In total, 15 systematic reviews and reviews met the inclusion criteria.
      Most of the systematic reviews were found to be medium quality on the AMSTAR
      checklist. Most commonly, systematic reviews and reviews evaluated active
      videogames. According to the results, evidence of the highest level and quality
      seems to support an increase in physical activity to light to moderate levels and
      energy expenditure, especially when playing active videogames that require both
      upper and lower body movements. In addition, sedentary games were shown to have
      potential in children's health education, especially in supporting changes in
      asthma- and diabetes-related behavior and in dietary habits. However, there are
      still several gaps in the knowledge. There is a need for further high-quality
      systematic reviews and research in the field of health games. 

PMID- 26196174
TI  - Comparing Outcomes of Kinect Videogame-Based Occupational/Physical Therapy Versus
      Usual Care.
AB  - OBJECTIVE: The purpose of this study was to assess the effectiveness of a game
      like exercise tool as a component of occupational and physical therapy treatment
      for patients with shoulder pain and impairment in an outpatient physical therapy
      clinic. MATERIALS AND METHODS: The product evaluated is a hands-free therapy
      (HFT) prototype, using Microsoft((r)) (Redmond, WA) KinectTM technology. HFT was
      designed as a home exercise program (HEP), or adjunct to a clinic-based exercise
      program, with the goal to improve patient compliance and outcomes by providing
      patients with continuous immediate feedback and engaging them in a game-like
      experience. Eight patients with shoulder injuries were randomly assigned to study
      groups. Outcomes in pain, range of motion, and function were assessed. The
      experimental group received six sessions using HFT; the control group received
      six sessions of treatment as usual. RESULTS: The research demonstrated that
      patient outcomes were as good in the group using HFT as outcomes achieved with
      usual care. HFT was found to be a useful adjunct in an outpatient therapy clinic,
      allowing patients to complete exercises with real-time feedback and minimal
      therapist oversight. CONCLUSIONS: These preliminary findings support the
      potential use of technology to provide an effective therapy and HEP system.
      Additional research utilizing a larger sample size is warranted to determine if
      this product can be an effective tool to improve HEP compliance and to determine
      the effectiveness of HFT as an adjunctive treatment in the clinic.

PMID- 26196175
TI  - Design and Evaluation of Virtual Reality-Based Therapy Games with Dual Focus on
      Therapeutic Relevance and User Experience for Children with Cerebral Palsy.
AB  - OBJECTIVE: Virtual reality (VR)-based therapy for motor rehabilitation of
      children with cerebral palsy (CP) is growing in prevalence. Although mainstream
      active videogames typically offer children an appealing user experience, they are
      not designed for therapeutic relevance. Conversely, rehabilitation-specific games
      often struggle to provide an immersive experience that sustains interest. This
      study aims to design and evaluate two VR-based therapy games for upper and lower
      limb rehabilitation and to evaluate their efficacy with dual focus on therapeutic
      relevance and user experience. MATERIALS AND METHODS: Three occupational
      therapists, three physiotherapists, and eight children (8-12 years old), with CP
      Level I-III on the Gross Motor Function Classification System, evaluated two
      games for the Microsoft((r)) (Redmond, WA) KinectTM for Windows and completed the
      System Usability Scale (SUS), Physical Activity Enjoyment Scale (PACES), and
      custom feedback questionnaires. RESULTS: Children and therapists unanimously
      agreed on the enjoyment and therapeutic value of the games. Median scores on the
      PACES were high (6.24+/-0.95 on the 7-point scale). Therapists considered the
      system to be of average usability (50th percentile on the SUS). The most
      prevalent usability issue was detection errors distinguishing the child's
      movements from the supporting therapist's. The ability to adjust difficulty
      settings and to focus on targeted goals (e.g., elbow/shoulder extension, weight
      shifting) was highly valued by therapists. CONCLUSIONS: Engaging both therapists
      and children in a user-centered design approach enabled the development of two VR
      based therapy games for upper and lower limb rehabilitation that are dually (a)
      engaging to the child and (b) therapeutically relevant.

PMID- 26196176
TI  - The Effects of Combining Videogame Dancing and Pelvic Floor Training to Improve
      Dual-Task Gait and Cognition in Women with Mixed-Urinary Incontinence.
AB  - OBJECTIVE: Many women over 65 years of age suffer from mixed urinary incontinence
      (MUI) and executive function (EF) deficits. Both incontinence and EF declines
      increase fall risk. The current study assessed EF and dual-task gait after a
      multicomponent intervention that combined pelvic floor muscle (PFM) training and
      videogame dancing (VGD). MATERIALS AND METHODS: Baseline (Pre1), pretraining
      (Pre2), and post-training (Post) neuropsychological and dual-task gait
      assessments were completed by 23 women (mean age, 70.4 years) with MUI. During
      the dual-task, participants walked and performed an auditory n-back task. From
      Pre2 to Post, all women completed 12 weeks of combined PFM and VGD training.
      RESULTS: After training (Pre2 to Post), the number of errors in the
      Inhibition/Switch Stroop condition decreased significantly, the Trail Making Test
      difference score improved marginally, and the number of n-back errors during dual
      task gait significantly decreased. A subgroup analysis based on continence
      improvements (pad test) revealed that only those subjects who improved in the pad
      test had significantly reduced numbers of n-back errors during dual-task gait.
      CONCLUSIONS: The results of this study suggest that a multicomponent intervention
      can improve EFs and the dual-task gait of older women with MUI. Future research
      is needed to determine if the training-induced improvements in these factors
      reduce fall risk.

PMID- 26196177
TI  - Use of the Wii Gaming System for Balance Rehabilitation: Establishing Parameters
      for Healthy Individuals.
AB  - OBJECTIVE: This study was designed to establish balance parameters for the
      Nintendo((r)) (Redmond, WA) "Wii FitTM" Balance Board system with three common
      games, in a sample of healthy adults, and to evaluate the balance measurement
      reproducibility with separation by age. SUBJECTS AND METHODS: This was a
      prospective, multivariate analysis of variance, cohort study design. Seventy-five
      participants who satisfied all inclusion criteria and completed an informed
      consent were enrolled. Participants were grouped into age ranges: 21-35 years
      (n=24), 36-50 years (n=24), and 51-65 years (n=27). Each participant completed
      the following games three consecutive times, in a randomized order, during one
      session: "Balance Bubble" (BB) for distance and duration, "Tight Rope" (TR) for
      distance and duration, and "Center of Balance" (COB) on the left and right sides.
      RESULTS: COB distributed weight was fairly symmetrical across all subjects and
      trials; therefore, no influence was assumed on or interaction with other "Wii
      Fit" measurements. Homogeneity of variance statistics indicated the assumption of
      distribution normality of the dependent variables (rates) were tenable. The
      multivariate analysis of variance included dependent variables BB and TR rates
      (distance divided by duration to complete) with age group and trials as the
      independent variables. The BB rate was statistically significant (F=4.725,
      P<0.005), but not the TR rate. The youngest group's BB rate was significantly
      larger than those of the other two groups. CONCLUSIONS: "Wii Fit" can
      discriminate among age groups across trials. The results show promise as a viable
      tool to measure balance and distance across time (speed) and center of balance
      distribution.

PMID- 26196179
TI  - Correction.

PMID- 26196178
TI  - Gaming and Conventional Exercises for Improvement of Arm Function After Stroke: A
      Randomized Controlled Pilot Study.
AB  - OBJECTIVE: The use of new technologies in rehabilitation, such as virtual reality
      and/or computerized gaming exercises, may be useful to enable patients to
      practice intensively in a motivating way. The objective of the present randomized
      controlled pilot study was to compare the effect of reach training using a target
      group specific-designed rehabilitation game to time-matched standardized
      conventional reach training on arm function after stroke. MATERIALS AND METHODS:
      Twenty chronic stroke patients were randomized to either the rehabilitation game
      group or the conventional training group. Both groups received three arm training
      sessions of 30 minutes each week, during a period of 6 weeks. Arm (the upper
      extremity part of Fugl-Meyer [FM] assessment) and hand (the Action Research Arm
      [ARA] test) functions were tested 1 week before (T0) and 1 week after (T1)
      training. A follow-up measurement was performed at 1 month after T1 (T2).
      RESULTS: ARA and FM scores improved significantly within both groups. Post hoc
      comparisons revealed significant increases in test scores between T0 and T1 and
      between T0 and T2 for both ARA and FM, but not for changes from T1 to T2. There
      were no significant differences between both groups for either clinical test.
      CONCLUSIONS: The present randomized controlled pilot study showed that both arm
      and hand function improved as much after training with a rehabilitation game as
      after time-matched conventional training.

PMID- 26196180
TI  - Rabies Postexposure Prophylaxis for Travelers Injured by Nonhuman Primates,
      Marseille, France, 2001-2014.
AB  - Most exposures of residents of Marseille to nonhuman primates occurred among
      unvaccinated adult travelers to Southeast Asia within the first 10 days of their
      arrival at 2 major tourist locations in Thailand and 1 in Indonesia. A small
      proportion of travelers received rabies immunoglobulin in the country of
      exposure. 

PMID- 26196181
TI  - Bean common mosaic virus Isolate Exhibits a Novel Pathogenicity Profile in Common
      Bean, Overcoming the bc-3 Resistance Allele Coding for the Mutated eIF4E
      Translation Initiation Factor.
AB  - Resistance against Bean common mosaic virus (BCMV) in Phaseolus vulgaris is
      governed by six recessive resistance alleles at four loci. One of these alleles,
      bc-3, is able to protect P. vulgaris against all BCMV strains and against other
      potyviruses; bc-3 was identified as the eIF4E allele carrying mutated eukaryotic
      translation initiation factor gene. Here, we characterized a novel BCMV isolate
      1755a that was able to overcome bc-2 and bc-3 alleles in common bean. Thus, it
      displayed a novel pattern of interactions with resistance genes in P. vulgaris,
      and was assigned to a new pathogroup, PG-VIII. The IVT7214 cultivar supporting
      the replication of BCMV-1755a was found to have the intact homozygous bc-3
      cleaved amplified polymorphic sequences marker and corresponding mutations in the
      eIF4E allele that confer resistance to BCMV isolates from all other pathogroups
      as well as to other potyviruses. The VPg protein of 1755a had seven amino acid
      substitutions relative to VPgs of other BCMV isolates unable to overcome bc-3.
      The 1755a genome was found to be a recombinant between NL1, US1 (both PG-I), and
      a yet unknown BCMV strain. Analysis of the recombination patterns in the genomes
      of NL1 and US1 (PG-I), NY15P (PG-V), US10 and RU1-OR (PG-VII), and 1755a (PG
      VIII), indicated that P1/HC-Pro cistrons of BCMV strains may interact with most
      resistance genes. This is the first report of a BCMV isolate able to overcome the
      bc-3 resistance allele, suggesting that the virus has evolved mechanisms to
      overcome multiple resistance genes available in common bean. 

PMID- 26196182
TI  - Effects of growth arrest and DNA damage-inducible protein 34 (GADD34) on
      inflammation-induced colon cancer in mice.
AB  - BACKGROUND: Growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a)
      is a family of GADD proteins that are induced by DNA damage. GADD34 protein has
      been suggested to regulate inflammation or host defense systems. However, the in
      vivo function of GADD34 in inflammation is still unclear. Long lasting
      inflammation, such as that seen in Crohn's disease and ulcerative colitis, is
      associated with a higher incidence of colorectal cancer (CRC). METHODS: Using a
      colitis-associated cancer model, we analysed GADD34-deficient (KO) mice to study
      the effect of GADD34 on colitis and colorectal tumorigenesis. RESULTS: We found a
      higher incidence of CRC in wild-type (WT) mice than in GADD34KO mice. Moreover,
      dextran sodium sulfate (DSS)-induced inflammatory responses were downregulated by
      GADD34 deficiency. The expression of pro-inflammatory mediators such as TNFalpha,
      IL-6, and iNOS/NOS2 was higher in the colons of WT mice than GADD34KO mice. IL-6
      is known to activate STAT3 signalling in colonic epithelial cells and
      subsequently induced epithelial proliferation. We found that IL-6-STAT3
      signalling and epithelial proliferation were higher in WT mice compared with
      GADD34KO mice. CONCLUSIONS: These results indicated that GADD34 upregulated pro
      inflammatory mediator production leading to a higher tumour burden following
      azoxymethane (AOM)/DSS treatment.

PMID- 26196183
TI  - Identification of a hypoxia-regulated miRNA signature in bladder cancer and a
      role for miR-145 in hypoxia-dependent apoptosis.
AB  - BACKGROUND: Hypoxia leads to the stabilisation of the hypoxia-inducible factor
      (HIF) transcription factor that drives the expression of target genes including
      microRNAs (miRNAs). MicroRNAs are known to regulate many genes involved in
      tumourigenesis. The aim of this study was to identify hypoxia-regulated miRNAs
      (HRMs) in bladder cancer and investigate their functional significance. METHODS:
      Bladder cancer cell lines were exposed to normoxic and hypoxic conditions and
      interrogated for the expression of 384 miRNAs by qPCR. Functional studies were
      carried out using siRNA-mediated gene knockdown and chromatin
      immunoprecipitations. Apoptosis was quantified by annexin V staining and flow
      cytometry. RESULTS: The HRM signature for NMI bladder cancer lines includes miR
      210, miR-193b, miR-145, miR-125-3p, miR-708 and miR-517a. The most hypoxia
      upregulated miRNA was miR-145. The miR-145 was a direct target of HIF-1alpha and
      two hypoxia response elements were identified within the promoter region of the
      gene. Finally, the hypoxic upregulation of miR-145 contributed to increased
      apoptosis in RT4 cells. CONCLUSIONS: We have demonstrated the hypoxic regulation
      of a number of miRNAs in bladder cancer. We have shown that miR-145 is a novel,
      robust and direct HIF target gene that in turn leads to increased cell death in
      NMI bladder cancer cell lines.

PMID- 26196184
TI  - Targeting LKB1 in cancer - exposing and exploiting vulnerabilities.
AB  - The LKB1 tumour suppressor is a serine/threonine kinase that functions as master
      regulator of cell growth, metabolism, survival and polarity. LKB1 is frequently
      mutated in human cancers and research spanning the last two decades have begun
      decoding the cellular pathways deregulated following LKB1 inactivation. This work
      has led to the identification of vulnerabilities present in LKB1-deficient tumour
      cells. Pre-clinical studies have now identified therapeutic strategies targeting
      this subset of tumours that promise to benefit this large patient population
      harbouring LKB1 mutations. Here, we review the current efforts that are underway
      to translate pre-clinical discovery of therapeutic strategies targeting LKB1
      mutant cancers into clinical practice. 

PMID- 26196187
TI  - Modulation and Functional Role of the Orientations of the N- and P-Domains of Cu+
      -Transporting ATPase along the Ion Transport Cycle.
AB  - Ion transport of different P-type ATPases is regulated similarly through the
      interplay of multiple protein domains. In the presence of ATP, binding of a
      cation to the ion binding site in the transmembrane helices leads to the
      phosphorylation of the P-domain, allowing ion transfer across the membrane. The
      details of the mechanism, however, are not clear. Here, we report the modulation
      of the orientation between the N- and P-domains of Cu(+)-transporting ATPase
      along the ion transport cycle using high-resolution nuclear magnetic resonance
      spectroscopy in solution. On the basis of residual dipolar coupling measurements,
      it is found that the interdomain orientation (relative openness) of the N- and P
      domains is distinctly modulated depending on the specific state of the N- and P
      domains along the ion translocation cycle. The two domains' relative position in
      the apo state is semiopen, whereas it becomes closed upon binding of ATP to the N
      domain. After phosphorylation of the P-domain and the release of ADP, the
      opening, however, becomes the widest among all the states. We reason such wide
      opening resulting from the departure of ADP prepares the N- and P-domains to
      accommodate the A-domain for interaction and, hence, promote ion transport and
      allow dephosphorylation of the P-domain. Such wide interdomain opening is
      abolished when an Asn to Asp mutation is introduced into the conserved DXXK motif
      located in the hinge region of the N- and P-domains of Cu(+)-ATPase, suggesting
      the indispensible role of the N- and P-interdomain orientation during ion
      transportation. Our results shed new light on the structural and mechanistic
      details of P-type ATPase function at large. 

PMID- 26196186
TI  - MDA-MB-231 breast cancer cells overexpressing single VEGF isoforms display
      distinct colonisation characteristics.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is a multifunctional
      cytokine that has important roles in angiogenesis. Our knowledge of the
      significance of VEGF isoforms in human cancer remains incomplete. METHODS:
      Bioluminescence imaging and transcriptomic analysis were used to study the
      colonisation capacity of the human breast cancer cells MDA-MB-231 controlling or
      overexpressing the VEGF165 or VEGF189 isoform (named cV-B, V165-B and V189-B,
      respectively) in nude mice. RESULTS: When injected into the bloodstream, V189-B
      cells induced less metastasis in the lungs and bone than V165-B and cV-B control
      cells, consistent with longer survival of these mice and delay in tumour uptake
      in the mice injected with a V189-B clone. Histological analysis confirmed that
      there were less alphaSMA-positive cells in the lungs of the mice injected with
      V189-B. In vitro V189-B cells decreased both cell invasion and survival. Using
      transcriptomic analysis, we identified a subset of 18 genes expressed
      differentially between V189 and V165 cell lines and in 120 human breast tumours.
      V165 was associated with poor prognosis, whereas V189 was not, suggesting a
      complex regulation by VEGF isoforms. Our results showed a negative correlation
      between the expression pattern of VEGF189 and the levels of expression of seven
      genes that influence metastasis. CONCLUSION: Our findings provide the first
      evidence that VEGF isoforms have different effects on breast cancer cell line
      colonisation in vivo.

PMID- 26196185
TI  - Endoplasmic reticulum ribosome-binding protein 1, RRBP1, promotes progression of
      colorectal cancer and predicts an unfavourable prognosis.
AB  - BACKGROUND: Ribosome-binding protein 1 (RRBP1) has been implicated in the
      regulation of unfolded protein response, which is involved in almost every aspect
      of cancer development. We aimed to explore the significance of RRBP1 in the
      progression and prognosis of colorectal cancer (CRC). METHODS: The study
      population consisted of 856 patients with stage I-III CRC from two hospitals.
      RRBP1 expression was examined by immunohistochemistry (IHC) in colorectal
      tissues. The correlation of RRBP1 expression and CRC occurrence was assessed in
      paired cancer-adjacent tissues. Factors contributing to prognosis were evaluated
      in a training-validation design with univariate and multivariate Cox analysis.
      Colorectal cancer aggressiveness caused by RRBP1 knockdown or overexpression was
      evaluated in CRC cells. RESULTS: RRBP1 was aberrantly overexpressed in CRC.
      Compared with low-RRBP1 patients, high-RRBP1 patients had shorter disease
      specific survival in the training (hazard ratio (HR), 2.423; 95% confidence
      interval (CI), 1.531-3.835) and validation cohorts (HR, 3.749; 95% CI, 2.166
      6.448) in multivariate Cox analysis. High-RRBP1 independently predicted a shorter
      disease-free survival (HR, 4.821; 95% CI, 3.220-7.218) in the validation cohort.
      RRBP1 knockdown reduced the aggressiveness of CRC cells in vitro and inhibited
      the growth of CRC xenografts in vivo. CONCLUSIONS: High RRBP1 expression
      facilitates CRC progression and predicts an unfavourable post-operative
      prognosis.

PMID- 26196188
TI  - Satisfaction of immediate or delayed switch to paliperidone palmitate in patients
      unsatisfied with current oral atypical antipsychotics.
AB  - Patient satisfaction with treatment is an important clinical index associated
      with the efficacy and adherence of treatment in schizophrenia. Although switching
      from oral antipsychotics to the long-acting injectable formulation may improve
      convenience, patient satisfaction has not been studied extensively. We carried
      out a 21-week, multicenter, randomized, open-label comparative study. A total of
      154 patients with schizophrenia unsatisfied with current oral atypical
      antipsychotics were assigned randomly to either immediate or delayed switching to
      paliperidone palmitate, the long-acting injectable formulation of paliperidone.
      The Medication Satisfaction Questionnaire (MSQ) and the Treatment Satisfaction
      Questionnaire for Medication (TSQM) were used to evaluate patient satisfaction
      with treatment, whereas the Positive and Negative Syndrome Scale (PANSS) and the
      Personal and Social Performance (PSP) scale were used to evaluate efficacy. From
      baseline to the final assessment, the MSQ score increased significantly in both
      groups, and the increase was greatest after the first administration of
      paliperidone palmitate in the immediate switch group. The scores of TSQM
      effectiveness, convenience, and global satisfaction as well as the PSP total
      score increased significantly, whereas the PANSS total score decreased
      significantly in both groups. The immediate switch group showed a significant
      improvement in the TSQM convenience score compared with the delayed switch group
      on oral antipsychotics during the comparison period. Most adverse events were
      minor and tolerable. In short, switching from oral atypical antipsychotics to
      paliperidone palmitate because of poor satisfaction significantly improved
      patient satisfaction, with comparable efficacy and tolerability. 

PMID- 26196190
TI  - Early severe preeclampsia with marked platelet dysfunction in association with
      essential thrombocytemia: case report and discussion.
AB  - Essential thrombocytemia--a classic myeloproliferative neoplasm characterized by
      persistent thrombocytosis--may associate both thrombotic and hemorrhagic events,
      as well as platelet dysfunction. Of all myeloproliferative neoplasms, essential
      thrombocytemia is more likely to be associated with pregnancy, because of a
      higher comparative incidence in younger patients. This association significantly
      increases the risk of pregnancy loss and of various pregnancy complications. We
      present a case of early severe preeclampsia with a critical and unusual evolution
      and life-threatening complications.

PMID- 26196189
TI  - Weight change during long-term treatment with lurasidone: pooled analysis of
      studies in patients with schizophrenia.
AB  - The objective of this analysis was to evaluate the effect of 12 months of
      treatment with lurasidone on weight in patients with schizophrenia. Post-hoc,
      observed-case analysis included pooled data from six studies on 40-160 mg/day
      lurasidone; two studies included active comparators (2-6 mg/day risperidone or
      200-800 mg/day quetiapine XR). Overall, 593 patients completed 12 months of
      treatment (N=471 lurasidone, N = 89 risperidone, N = 33 quetiapine XR). The mean
      baseline weight was 72.8, 80.8, and 72.4 kg in the lurasidone, risperidone, and
      quetiapine XR groups, respectively. The mean weight change at month 12 was -0.4
      kg with lurasidone, +2.6 kg with risperidone, and +1.2 kg with quetiapine XR.
      Weight gain of at least 7% from study baseline was observed in 16.0, 25.8, and
      15.2% of patients, and weight loss of at least 7% was seen in 18.5, 6.7, and 9.1%
      of patients treated with lurasidone, risperidone, and quetiapine XR,
      respectively. A shift from normal/underweight baseline BMI status to
      overweight/obese at month 12 occurred in 10.2, 27.6, and 15.0% of patients in the
      lurasidone, risperidone, and quetiapine XR groups, respectively. Conversely,
      14.3, 1.7, and 7.7% of patients, respectively, shifted from overweight/obese to
      normal/underweight. In summary, a low potential for clinically significant weight
      gain was observed in patients with schizophrenia treated continuously with
      lurasidone for 12 months.

PMID- 26196192
TI  - Correction of factor XI deficiency by liver transplantation.
AB  - Orthotopic liver transplantation for other diseases typically results in a
      coincidental cure for hemophilia A and B; however, long-term outcomes of liver
      transplant in hemophilia C are not very well described. Herein, the authors
      report a patient of severe congenital factor XI (FXI) deficiency who received an
      orthotopic liver transplant. The authors discuss the perioperative management and
      long-term outcomes. The normalization of his FXI levels confirms that the liver
      is the most clinically relevant site of synthesis of FXI. 

PMID- 26196193
TI  - Ovine platelet function is unaffected by extracorporeal membrane oxygenation
      within the first 24 h.
AB  - This study investigated platelet dysfunction during short-term extracorporeal
      membrane oxygenation (ECMO) and secondarily to determine if hyperoxaemia
      contributes to this dysfunction. Healthy sheep were anaesthetized and maintained
      on ECMO for either 2 or 24 h, with or without induction of smoke inhalation acute
      lung injury. A specialized animal-operating theatre was used to conduct the
      experimentation. Forty-three healthy female sheep were randomized into either a
      test or a control group. Following anaesthesia, test groups received ECMO +/-
      smoke inhalation acute lung injury (SALI), whereas control groups were maintained
      with ventilation only +/- SALI. Physiological, biochemical and coagulation data
      were obtained throughout via continuous monitoring and blood sampling. Platelet
      function was quantified through whole blood impedance aggregometry using
      Multiplate. Ovine platelet activity induced by adenosine diphosphate (ADP) and
      collagen was unaffected during the first 24 h of ECMO. However, progressive
      divergence of ADP-induced platelet activity was noted at cessation of the
      experiment. PaO2 was inversely related to ADP-dependent platelet activity in the
      ECMO groups--a relationship not identified in the control groups. ADP and
      collagen-dependent platelet activity are not significantly affected within the
      first 24 h of ECMO in sheep. However, dysfunction in ADP-dependent platelet
      activity may have continued to develop if observed beyond 24 h. Hyperoxaemia
      during ECMO does appear to affect how platelets react to ADP and may contribute
      to this developing dysfunction. Long-term animal models and investigation in
      clinical animals are warranted to fully investigate platelet function during
      ECMO.

PMID- 26196194
TI  - Is mean platelet volume a new activity criteria in Behcet's disease?
AB  - The aim of this study was to assess mean platelet volume (MPV) and its
      relationship with disease activity in patients with Behcet's disease. Thirty-six
      patients with an age of 38.9 +/- 11 (mean +/- SD) years and 40 controls aged 36.5
      +/- 12 (mean +/- SD) years were enrolled the study. Demographic data, erythrocyte
      sedimentation rate (ESR), C-reactive protein (CRP), MPV, clinical findings such
      as oral aphthae, genital aphthae, erythema nodosum, acne, central nervous system
      involvement, uveitis, arthritis and arthralgia were all recorded. The MPV value
      in patients with Behcet's disease was 8.06 +/- 1.0 (mean +/- SD) and the MPV
      value of the control participants was 7.45 +/- 0.6 (mean +/- SD). MPV was
      statistically higher in patients with Behcet's disease than in the controls (P =
      0.003). There were also significant differences between patients and controls
      according to ESR and CRP values (P < 0.001 and P = 0.001, respectively). MPV was
      positively correlated with arthralgia (P < 0.001, r = 0.438), arthritis (P =
      0.008, r = 0.307), erythema nodosum (P = 0.002, r =  0.354), central nervous
      system involvement (P = 0.002, r = 0.357), acne (P = 0.008, r = 0.312), genital
      aphthae (P < 0.001, r = 0.401) and oral aphthae (P = 0.001 r = 0.377). MPV can be
      easily obtained from the patients. It was a cheap and practical method. In the
      future, MPV may be used as a new marker to detect the activation of BD.

PMID- 26196195
TI  - Nonacog alfa: an analysis of safety data from six prospective clinical studies in
      different patient populations with haemophilia B treated with different
      therapeutic modalities.
AB  - Nonacog alfa is a recombinant factor IX (FIX) product indicated for treatment and
      prevention of bleeding episodes in patients with haemophilia B. This posthoc
      analysis evaluated the safety of nonacog alfa in key clinical studies across 15
      years. Data were pooled from six prospective studies that utilized on-demand,
      prophylactic and preventive nonacog alfa regimens: three open-label,
      nonrandomized studies that assessed efficacy and safety; a bioequivalence study
      of original and reformulated nonacog alfa; an open-label, randomized study that
      compared on-demand and prophylactic treatment; and a noninterventional
      observational registry study that evaluated safety. Safety assessments included
      adverse events, serious adverse events (SAEs) and events of special interest. In
      total, 412 patients received nonacog alfa treatment. Adverse events occurred in
      220 patients (53.4%), the most common being pyrexia (n = 63), nasopharyngitis (n
      = 53) and cough (n = 52). Forty-eight patients (11.7%) experienced treatment
      related adverse events; the most common were hypersensitivity (n = 6), urticaria
      (n = 6), FIX inhibition (n = 5) and pyrexia (n = 4). Seventy-four patients
      (18.0%) developed SAEs. Thirty-seven events of special interest occurred in 31
      (7.5%) patients. Events of special interest included allergic-type manifestations
      (n = 15), inhibitor development (n = 5), lack of effect (n = 8), red blood cell
      agglutination in tubing or syringe (n = 7), and thrombogenicity (n = 2). Six
      patients (1.5%) withdrew due to seven adverse events: hypersensitivity (n = 3),
      drug eruption, pruritic rash, urticaria and decreased therapeutic response (n = 1
      each). Four patients died during the study; no deaths were related to study
      medication. This pooled safety analysis in haemophilia B patients confirmed the
      safety of nonacog alfa across various patient populations.

PMID- 26196196
TI  - Pegasparaginase treatment alters thrombin generation by modulating the protein C
      and S system in acute lymphoblastic leukaemia/lymphoma.
AB  - Paediatric patients with acute lymphoblastic leukaemia/lymphoma treated with
      pegasparaginase are at an increased risk of thrombosis. We evaluated changes in
      thrombin generation in the presence and absence of thrombomodulin using paired
      plasma samples collected from paediatric patients treated with pegasparaginase.
      Postpegasparaginase samples were significantly less sensitive to reductions in
      thrombin generation in the presence of thrombomodulin compared with
      prepegasparaginase, suggesting reduced protein C and S activity. This
      corresponded to a significant decrease in protein C and protein S antigen.
      Alterations in the protein C and S pathway may contribute to the increased risk
      of thrombosis in patients treated with pegasparaginase. 

PMID- 26196197
TI  - Can rotational thromboelastometry predict septic disseminated intravascular
      coagulation?
AB  - Rotational thromboelastometry (ROTEM), known as point-of-care testing, has been
      incorporated into various kinds of postsurgical management. However, the utility
      of ROTEM for rapid diagnosis of sepsis-induced disseminated intravascular
      coagulation (DIC) has not been investigated. This retrospective study includes 13
      sepsis patients who underwent ROTEM in our emergency department in 2013. All
      patients were divided into two groups on the basis of the presence of DIC
      diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We
      evaluated the demographics, clinical characteristics, laboratory data, ROTEM test
      and outcomes for each patient. The correlations between JAAM DIC score and
      significantly different parameters by univariate analysis and receiver operating
      characteristic (ROC) analysis were performed to assess the accuracy of the
      variables. There were seven and six patients in the DIC group and non-DIC group,
      respectively. The DIC group showed significantly longer prothrombin times,
      international normalized ratio of prothrombin time and clotting times (CTs) in
      the EXTEM test, and higher fibrinogen and fibrin degradation products and D
      dimer. The CT in EXTEM test was correlated more with JAAM DIC score (r = 0.798),
      than the standard coagulation test. These parameters were accurate predictors in
      the diagnosis of septic DIC, with an AUC of 0.952, and a cut-off value of more
      than 46.0 s, resulting in a sensitivity of 100.0% and a specificity of 83.3%. CT
      in the EXTEM test was a single reliable indicator of sepsis-induced DIC diagnosed
      by the JAAM DIC score, and strongly associated with severity of DIC.

PMID- 26196198
TI  - Continuous 48-Hour Wireless Esophageal pH Monitoring in Children: Comparison
      Between Days 1 and 2.
AB  - AIM: Comparison of days 1 and 2 to each other and to the total recording of 48
      hours in continuous 48-hour wireless esophageal pH monitoring in children.
      METHODS: A retrospective study of 105 patients who underwent 48-hour pH
      monitoring (Bravo) studies between January 1992 and June 2010 was performed.
      Reflux variables were compared between days 1 and 2. RESULTS: A total of 58
      (55.2%) patients were men. The number of reflux episodes, number of long reflux
      >5 minutes, duration of the longest reflux (minutes), time pH <4 (minutes),
      fraction time pH <4 supine (%), fraction time pH <4 upright (%), reflux index,
      and DeMeester score did not differ between days 1 and 2. CONCLUSIONS: No effect
      of anesthesia was observed on the gastroesophageal reflux parameters on children.

PMID- 26196199
TI  - Effectiveness of Enteral Versus Oral Nutrition With a Medium-Chain Triglyceride
      Formula to Prevent Malnutrition and Growth Impairment in Infants With Biliary
      Atresia.
AB  - OBJECTIVES: The aim of this study was to compare the effectiveness of oral (PO)
      versus enteral nutrition (EN) medium-chain triglyceride (MCT) containing-formula
      to prevent malnutrition and growth impairment in infants with biliary atresia
      (BA) waiting for a liver transplant. METHODS: A total of 15 infants, 3 to 9
      months old with BA were included. They were randomly assigned to either PO or EN.
      For 12 weeks, both groups received an MCT formula fortified with glucose polymers
      and corn oil to reach a caloric density between 0.8 and 1 kcal/mL. The formula
      given to the PO group was administered ad libitum and that given via EN was
      infused through a nasogastric tube to reach 140% of the energy intake recommended
      by the Dietary Recommended Intake guidelines. Protein intake was adjusted to 4 to
      5 g/kg present weight. Outcome variables were growth and nutritional status
      evaluated periodically by anthropometric indicators. Biochemical and
      hematological variables were evaluated through the study. RESULTS: Baseline
      clinical, nutritional, biochemical, and hematological variables showed no
      differences between the study groups. Baseline length/age was <-2 SD in 10 of the
      15 patients; in the PO group, it fell <-3 SD, whereas in the EN group, it
      remained stable. Head circumference z score dropped 0.6 SD in the PO group,
      whereas in the EN group it remained stable. Triceps skinfold values improved in
      the infants taking EN, P < 0.001. The frequency of adverse effects--respiratory
      infection and diarrhea--was higher in the EN group. No biochemical or
      hematological differences were observed between the study groups throughout the
      study. CONCLUSIONS: A 12-week EN trial with an MCT-fortified formula prevented
      malnutrition and growth impairment in infants with BA waiting for a liver
      transplant.

PMID- 26196200
TI  - Clinical Characteristics of 2 Groups of Children With Feeding Difficulties.
AB  - OBJECTIVES: The primary aim of this study was to describe and compare the
      clinical characteristics of 2 groups of children presenting to a feeding clinic:
      children with autism spectrum disorder (ASD) and children with a nonmedically
      complex history (NMC). A secondary aim was to compare participants according to
      the degree of oral motor impairment, presence of oral hypersensitivity, and
      clinically significant parent stress. METHODS: Children with feeding difficulties
      ages between 2 and 6 years were recruited. Prospective data were collected on
      dietary intake, general development, mealtime behaviors, oral motor skills, oral
      sensory processing, and parental stress via parent questionnaire and clinical
      assessment. RESULTS: In total, 68 children (ASD = 33 and NMC  = 35) participated
      in the study. Both groups presented with a large number of difficult mealtime
      behaviors. Although stress was elevated in both groups, parents of children in
      the ASD group reported significantly higher stress levels than those with
      children in the NMC group (mean difference 27.3 on a percentile scale, 95%
      confidence interval [CI] 15.5-39.2, P < 0.01). Across both groups, the majority
      of children presented with mild-to-moderate oral motor impairments (ASD = 28,
      85%; NMC = 28, 80%). Children with heightened oral sensory sensitivity consumed
      significantly fewer unprocessed fruits and vegetables (mean difference 3.3 foods,
      95% CI 1.3-5.3, P < 0.01), and their parents reported a significantly greater
      frequency of difficult mealtime behaviors (mean difference 5.8 behaviors, 95% CI
      3.4-8.1, P < 0.01). CONCLUSIONS: Features of feeding difficulty presented
      similarly across the ASD and NMC groups in this study. Oral motor impairment,
      oral sensory sensitivity, and parental stress should not be overlooked in the
      management of children with feeding difficulties, regardless of etiology.

PMID- 26196201
TI  - Pilot Study Evaluating Efficacy of 2 Regimens for Hypovitaminosis D Repletion in
      Pediatric Inflammatory Bowel Disease.
AB  - OBJECTIVES: Vitamin D is critical for skeletal health; hypovitaminosis D is
      common in pediatric inflammatory bowel disease (IBD), yet optimal repletion
      therapy is not well studied. We aimed to conduct a pilot trial comparing the
      efficacy of 2 vitamin D regimens of weekly dosing for the repletion of
      hypovitaminosis D in pediatric IBD. METHODS: Subjects identified from our IBD
      clinic with 25-hydroxyvitamin D (25[OH]D) concentrations <30 ng/mL were
      randomized to 10,000 (n = 18) or 5000 (n = 14) IU of oral vitamin D3/10 kg body
      weight per week for 6 weeks. Serum 25(OH)D, Ca, and parathyroid hormone
      concentrations were measured at baseline, week 8, and week 12. RESULTS: In the
      higher dosing group, serum 25(OH)D increased from 23.7 +/- 8.5 ng/mL at baseline
      to 49.2 +/- 13.6 ng/mL at 8 weeks; P < 0.001. In the lower dosing group, serum
      25(OH)D increased from 24.0 +/- 7.0 ng/mL at baseline to 41.5 +/- 9.6 ng/mL at 8
      weeks; P < 0.001. At 12 weeks, serum 25(OH)D concentrations were 35.1 +/- 8.4 and
      30.8 +/- 4.2 ng/mL for the higher and lower dose regimens, respectively. Mean
      serum Ca and parathyroid hormone concentrations did not significantly change
      during the study. No patient exhibited hypercalcemia, and no serious adverse
      events occurred. CONCLUSIONS: Both treatment arms were safe and effective at
      normalizing vitamin D nutriture in pediatric IBD. Although significant repletion
      of 25(OH)D concentration was achieved in both dosing groups at 8 weeks, this
      effect was lost by the 12-week follow-up. Maintenance vitamin D therapy following
      initial repletion is likely required to maintain long-term normalized vitamin D
      status.

PMID- 26196202
TI  - In Vitro Gluten Challenge Test for Celiac Disease Diagnosis.
AB  - OBJECTIVES: The in vitro gluten challenge test is an important diagnostic
      modality in celiac disease (CD), especially in patients who begin treatment with
      a gluten-free diet before adequate diagnostic workup or in cases with atypical
      CD. Available literature was reviewed regarding the accuracy of the in vitro
      gluten challenge test for CD diagnosis. METHODS: MEDLINE, Scopus, and Google
      Scholar were searched, and studies that used serology and bowel biopsy as the
      criterion standard for diagnosis were included in our study. Data on authors,
      publication year, characteristics of the patient and control groups, patients'
      diet, duration of the gluten challenge test, histology findings, endomysial
      antibody (EMA) and anti-tissue transglutaminase (tTG) levels, CD markers, and
      intercellular cell adhesion molecule-1, and human leukocyte antigens before and
      after the gluten challenge test were extracted. RESULTS: Overall, 15 studies were
      included in this meta-analysis. Pooled sensitivity %/specificity % was 84/99 for
      EMA after the challenge, 52/96 for EMA without the challenge, 95.5/98.3 for anti
      tTG after the challenge, and 95.1/98.3 for anti-tTG without the challenge test.
      Sensitivity/specificity for immunological markers were 89/97 for the percentage
      of CD25+-lamina propria lymphocytes, 96/91 for the percentage of CD3+-lamina
      propria lymphocytes, and 96.1/85.7 for the percentage of intercellular cell
      adhesion molecule-1-lamina propria lymphocytes. The factors that increased the
      sensitivity of EMA were longer test duration, and the evaluation of patients on a
      gluten-containing diet or short-term gluten-free diet. CONCLUSIONS: The in vitro
      gluten challenge test can be a useful part of the diagnostic workup of CD, rather
      than only a model to evaluate its mechanisms.

PMID- 26196203
TI  - Trypsin is a Potential Confounder in Calprotectin Results.

PMID- 26196204
TI  - Abdominal X-ray in Pediatric Acute Severe Colitis and Radiographic Predictors of
      Response to Intravenous Steroids.
AB  - BACKGROUND: Abdominal x-ray (AXR) can identify complications in acute severe
      colitis (ASC) and may assist in selecting high-risk children for early aggressive
      treatment. We aimed to describe AXR findings in pediatric ASC and to explore
      radiological predictors of response to intravenous corticosteroid (IVCS) therapy.
      METHODS: A total of 56 children with ASC were included in a multicenter,
      retrospective 1-year cohort study (41% boys, mean age 12.1 +/- 4.2). Radiographs
      of responders to IVCS and those requiring second-line salvage therapy by
      discharge were analyzed independently by 2 blinded radiologists. RESULTS: A total
      of 33 responders to IVCS were compared with 23 nonresponders. The day-3 Pediatric
      Ulcerative Colitis Activity Index (PUCAI) score was significantly higher in
      nonresponders (63 +/- 16 vs 46 +/- 21, P = 0.001). The mean transverse colon
      luminal diameter was 30 +/- 16 mm in responders and 38 +/- 16 mm in nonresponders
      (P = 0.94). The upper range of transverse colonic diameter in children <12 years
      was ~40 mm, whereas in older children it was 60 mm as accepted in adults.
      Ulcerations and megacolon seen on AXR were associated with nonresponse to IVCS (P
      = 0.006 and 0.064, respectively). CONCLUSIONS: The presence of mucosal
      ulcerations and megacolon on AXR could be considered in the risk stratification
      of children with ASC for early aggressive treatment, together with the previously
      known day-3 and day-5 Pediatric Ulcerative Colitis Activity Index scores,
      albumin, and C-reactive protein.

PMID- 26196206
TI  - Small Bowel Bacterial Overgrowth in Children.
AB  - OBJECTIVES: The aim of study was to perform a comprehensive review of the
      pathogenesis, available diagnostic procedures, prevalence, clinical
      manifestations, and consequences of small bowel bacterial overgrowth (SBBO) as
      well as treatment options in the pediatric population. METHODS: A literature
      search including MEDLINE, PubMed, and Web of Science databases was performed.
      RESULTS: SBBO is found in a variety of childhood conditions in which the normal
      homeostatic mechanisms restricting bacterial colonization in the small bowel are
      disturbed by congenital or acquired anatomical abnormalities, diminished gastric
      acid secretion, congenital alteration of intestinal motility or acquired small
      bowel diseases, or other chronic disorders including primary or acquired
      immunodeficiency. Data show that SBBO may be an underrecognized cause of
      pediatric morbidity. Although several diagnostic tests for SBBO determination are
      available, each has its drawbacks and limitations. Indeed, there is still no
      "criterion standard" for SBBO diagnosis in the pediatric population. Owing to
      lack of established guidelines and few published interventional studies that
      assess the effectiveness of SBBO therapy, treatment of children with SBBO remains
      empiric and comprises antibiotic or probiotic therapy. CONCLUSIONS: Further
      research is needed to determine the clinical impact of SBBO and to establish
      diagnostic and therapeutic guidelines applicable to children.

PMID- 26196207
TI  - Temporal Cortical Plasticity in Single-Sided Deafness: A Functional Imaging
      Study.
AB  - HYPOTHESIS: To refine and extend the knowledge on cortical plasticity in single
      sided deafness (SSD) by assessing magnetoencephalographic imaging in a well
      defined group of subjects. BACKGROUND: SSD causes difficulties with directional
      hearing, signal extraction in noise, and multispeaker identification and
      separation. In SSD, the ipsilateral auditory cortex is never powerfully driven by
      sound, which may lead to plastic change and contribute to higher-order
      psychoacoustic dysfunction beyond loss of a peripheral sound sensor. STUDY
      DESIGN: A cross-sectional study on 12 subjects with long-term, adult-onset,
      nontraumatic SSD and 12 normal-hearing controls was conducted using
      magnetoencephalographic imaging, magnetic resonance imaging, and validated
      hearing instruments. Pure-tone stimuli at five frequencies were presented to each
      hearing ear individually. M100 activation peak times of the ipsilateral and
      contralateral auditory cortices were analyzed. RESULTS: Controls showed an M100
      interhemispheric mean latency difference of 6.6 milliseconds. In contrast,
      subjects with SSD exhibited a mean of 1.7 milliseconds. This loss of
      interhemispheric latency difference was statistically significant (p < 0.05,
      analysis of variance with repeated measures). SSD subjects confirmed degraded
      hearing function on both Hearing Handicap Inventory for Adults (p < 0.001) and
      Speech, Spatial, and Qualities of Hearing Scale instruments (p < 0.001).
      CONCLUSION: SSD disrupts M100 latency difference between the two hemispheres to
      sound stimulation. This finding may represent maladaptive temporal cortical
      plasticity because of loss of a peripheral sensor. Based on this premise, a new
      generation of neurophysiologically inspired auditory treatments to correct or
      mitigate central consequences of SSD may be considered to optimize hearing in
      individuals with only one functional ear.

PMID- 26196208
TI  - Initial UK Experience With a Novel Magnetic Transcutaneous Bone Conduction
      Device.
AB  - OBJECTIVE: To assess outcomes with a new transcutaneous bone conduction hearing
      aid. PATIENTS: Patients that underwent implantation with the transcutaneous bone
      conduction device between November 2013 and May 2014. INTERVENTION: Hearing
      rehabilitation using the BAHA Attract. MAIN OUTCOME MEASURES: Quality of life
      measures using Glasgow benefit inventory (GBI) and clinically oriented scale of
      improvement (COSI). Audiological outcome using word discrimination score.
      RESULTS: Ten patients were implanted. Significant improvement in GBI and COSI
      scores comparing preimplantation and postimplantation. An increase in word
      discrimination scores at 30 dBA, with an increase from 0% unaided to a mean of
      50% with the magnetic transcutaneous bone conduction aid and at 50 dBA with an
      increase from a mean of 31.7% to 88.3%. However, the word discrimination score
      increase at 30, 50, and 60 dBA was not statistically significant (p = 0.25;
      Wilcoxon). CONCLUSION: There was a high level of satisfaction with the device
      with significant increases in GBI and COSI scores in patients who were previously
      aided with an acoustic aid. The absence of daily skin hygiene appealed to
      patients.

PMID- 26196209
TI  - Dose Effect of Intratympanic Dexamethasone for Idiopathic Sudden Sensorineural
      Hearing Loss: 24 mg/mL Is Superior to 10 mg/mL.
AB  - OBJECTIVE: To compare outcomes in patients with idiopathic sudden sensorineural
      hearing loss (ISSNHL) treated with intratympanic (IT) dexamethasone (DEX) at
      either 10 mg/mL or 24 mg/mL. STUDY DESIGN: Retrospective case series. SETTING:
      Tertiary referral center. PATIENTS: Thirty-seven adults with ISSNHL.
      INTERVENTIONS: In addition to concurrent prednisone taper, patients received a
      series of IT DEX injections for 2 weeks with either 10 mg/mL or 24 mg/mL. MAIN
      OUTCOME MEASURE: Greater than 30-dB improvement in pure-tone average (PTA).
      RESULTS: Baseline characteristics were similar between groups. Mean follow-up was
      10 weeks. Ten (53%) of 19 patients treated with 24 mg/mL had greater than 30-dB
      improvement in PTA compared with 3 (17%) of 18 treated with 10 mg/mL (p = 0.0382,
      Fisher's exact test). There was a trend toward improved word recognition score
      outcome with 24 mg/mL. The interval between onset and initiation of IT DEX
      significantly affected outcome, with earlier treatment resulting in greater
      improvement in PTA and word recognition score. Multivariate logistic regression
      confirmed that IT DEX dose and interval to starting treatment were both
      independent predictors of PTA outcome. Change in PTA was not significantly
      affected by age, sex, pretreatment hearing levels, or concurrent treatment with
      hyperbaric oxygen. CONCLUSION: To our knowledge, this is the first demonstration
      of superiority of IT DEX at 24 mg/mL for the treatment of ISSNHL, with
      significantly better recovery of PTA. Our data suggest that treatment should be
      initiated as soon as possible. A prospective randomized trial to confirm the
      optimal dose is warranted.

PMID- 26196210
TI  - Response to Letter to the Editor: "Cervical Spine Dysfunctions in Patients with
      Chronic Subjective Tinnitus".

PMID- 26196211
TI  - Near-IR Broadband-Absorbing trans-Bisphosphine Pt(II) Bisacetylide Complexes:
      Preparation and Study of the Photophysics.
AB  - Broadband near-IR absorbing trans-bis(trialkylphosphine) Pt(II) bisacetylide
      binuclear complex (Pt-1) was prepared with boron-dipyrromethene (Bodipy) and
      styrylBodipy acetylide ligands. Pt-1 shows strong absorption bands at 731 and 503
      nm. Singlet energy transfer (EnT) and efficient intersystem crossing of the
      central coordinated Bodipy ligand were proposed to be responsible for the
      efficient funneling of the excitation energy to the triplet-state manifold.
      Reference complexes containing only a single Bodipy ligand were prepared for
      comparison (with styrylBodipy ligand Pt-0 or Bodipy ligand Pt-2). The molecular
      structures were confirmed by single-crystal X-ray diffraction. The photophysical
      properties were studied with steady-state and time-resolved transient absorption
      spectroscopies, electrochemical characterization, and density functional
      theory/time-dependent density functional theory calculations. Dual fluorescence
      was observed for Pt-1. Singlet EnT in Pt-1 was proposed based on the fluorescence
      quenching/excitation spectra, and femtosecond transient absorption spectra
      (energy transfer rate constant kEnT = 2.2 * 10(10) s(-1)). With nanosecond
      transient absorption spectra, intramolecular triplet-state energy transfer in Pt
      1 was proved. Gibbs free energy changes of charge separation indicate that the
      photoinduced intramolecular electron transfer in Pt-1 is thermodynamically
      prohibited. Intermolecular triplet transfer between Pt-2 and L-1 was studied with
      nanosecond transient absorption spectra; the EnT rate and energy transfer
      efficiency were determined as 3.6 * 10(4) s(-1) and 94.5%, respectively. The
      singlet oxygen ((1)O2) photosensitizing of Pt-1 was improved as compared to the
      complexes containing only a single visible-light-absorbing chromophore. 

PMID- 26196212
TI  - Phosphido- and Amidozirconocene Cation-Based Frustrated Lewis Pair Chemistry.
AB  - Methyl abstraction from neutral [Cp2ZrMe(ERR')] complexes 1 (E = N, P; R, R' =
      alkyl, aryl) with either B(C6F5)3 or [Ph3C][B(C6F5)4] results in the formation of
      [Cp2Zr(ERR')][X] complexes 2 (X(-) = MeB(C6F5)3(-), B(C6F5)4(-)). The X-ray
      structure of amido complexes [Cp2Zr(NPh2)][MeB(C6F5)3] (2d) and
      [Cp2Zr(N(t)BuAr)][B(C6F5)4] (2e', Ar = 3,5-C6H3(CH3)2) is reported, showing a
      sterically dependent Zr/N-pi interaction. Complexes 2 catalyze the hydrogenation
      of electron-rich olefins and alkynes under mild conditions (room temperature, 1.5
      bar H2). Complex 2e binds CO2, giving [Cp2Zr(CO2)(N(t)BuAr)]2[MeB(C6F5)3]2 (3e).
      Amido complex 2d reacts with benzaldehyde yielding
      [Cp2Zr(OCH2Ph)((OC)PhNPh2)][MeB(C6F5)3] (7d). Phosphido complex
      [Cp2Zr(PCy2)][MeB(C6F5)3] (2a) reacts with diphenylacetylene to yield frustrated
      Lewis pair [Cp2Zr(PhCCPh)(PCy2)][MeB(C6F5)3] (8a) which further reacts with a
      range of carbonyl substrates. 

PMID- 26196213
TI  - Convergent One-Pot Oxidative [n + 1] Approaches to Spiroacetal Synthesis.
AB  - Two one-pot oxidative annulative approaches to spiroacetal synthesis are
      described. One approach uses a Lewis acid mediated Ferrier reaction in the
      fragment-coupling stage followed by DDQ-promoted oxidative carbon-hydrogen bond
      cleavage and cyclization. An alternative approach employs a Heck reaction for
      fragment coupling followed by DDQ-mediated enone formation and cyclization. These
      strategies provide convergent routes to common subunits in natural products,
      medicinal agents, and chemical libraries under mild reaction conditions. 

PMID- 26196214
TI  - 20 Years of Air-Water Gas Exchange Observations for Pesticides in the Western
      Arctic Ocean.
AB  - The Arctic has been contaminated by legacy organochlorine pesticides (OCPs) and
      currently used pesticides (CUPs) through atmospheric transport and oceanic
      currents. Here we report the time trends and air-water exchange of OCPs and CUPs
      from research expeditions conducted between 1993 and 2013. Compounds determined
      in both air and water were trans- and cis-chlordanes (TC, CC), trans- and cis
      nonachlors (TN, CN), heptachlor exo-epoxide (HEPX), dieldrin (DIEL),
      chlorobornanes (SigmaCHBs and toxaphene), dacthal (DAC), endosulfans and
      metabolite endosulfan sulfate (ENDO-I, ENDO-II, and ENDO SUL), chlorothalonil
      (CHT), chlorpyrifos (CPF), and trifluralin (TFN). Pentachloronitrobenzene (PCNB
      and quintozene) and its soil metabolite pentachlorothianisole (PCTA) were also
      found in air. Concentrations of most OCPs declined in surface water, whereas some
      CUPs increased (ENDO-I, CHT, and TFN) or showed no significant change (CPF and
      DAC), and most compounds declined in air. Chlordane compound fractions TC/(TC +
      CC) and TC/(TC + CC + TN) decreased in water and air, while CC/(TC + CC + TN)
      increased. TN/(TC + CC + TN) also increased in air and slightly, but not
      significantly, in water. These changes suggest selective removal of more labile
      TC and/or a shift in chlordane sources. Water-air fugacity ratios indicated net
      volatilization (FR > 1.0) or near equilibrium (FR not significantly different
      from 1.0) for most OCPs but net deposition (FR < 1.0) for SigmaCHBs. Net
      deposition was shown for ENDO-I on all expeditions, while the net exchange
      direction of other CUPs varied. Understanding the processes and current state of
      air-surface exchange helps to interpret environmental exposure and evaluate the
      effectiveness of international protocols and provides insights for the
      environmental fate of new and emerging chemicals. 

PMID- 26196215
TI  - Broad-Bandwidth Chiral Sum Frequency Generation Spectroscopy for Probing the
      Kinetics of Proteins at Interfaces.
AB  - The kinetics of proteins at interfaces plays an important role in biological
      functions and inspires solutions to fundamental problems in biomedical sciences
      and engineering. Nonetheless, due to the lack of surface-specific and structural
      sensitive biophysical techniques, it still remains challenging to probe protein
      kinetics in situ and in real time without the use of spectroscopic labels at
      interfaces. Broad-bandwidth chiral sum frequency generation (SFG) spectroscopy
      has been recently developed for protein kinetic studies at interfaces by tracking
      the chiral vibrational signals of proteins. In this article, we review our recent
      progress in kinetic studies of proteins at interfaces using broad-bandwidth
      chiral SFG spectroscopy. We illustrate the use of chiral SFG signals of protein
      side chains in the C-H stretch region to monitor self-assembly processes of
      proteins at interfaces. We also present the use of chiral SFG signals from the
      protein backbone in the N-H stretch region to probe the real-time kinetics of
      proton exchange between protein and water at interfaces. In addition, we
      demonstrate the applications of spectral features of chiral SFG that are typical
      of protein secondary structures in both the amide I and the N-H stretch regions
      for monitoring the kinetics of aggregation of amyloid proteins at membrane
      surfaces. These studies exhibit the power of broad-bandwidth chiral SFG to study
      protein kinetics at interfaces and the promise of this technique in research
      areas of surface science to address fundamental problems in biomedical and
      material sciences. 

PMID- 26196217
TI  - Enterovirus A71 Meningoencephalitis Outbreak, Rostov-on-Don, Russia, 2013.
AB  - Seventy-eight cases of enterovirus infection, including 25 neuroinfections,
      occurred in Rostov-on-Don, Russia, during May-June 2013. The outbreak was caused
      by an enterovirus A type 71 (EV-A71) subgenotype C4 lineage that spread to
      neighboring countries from China ~3 years earlier. Enterovirus associated
      neuroinfection may emerge in areas with a preceding background circulation of EV
      A71 with apparently asymptomatic infection. 

PMID- 26196218
TI  - A Facile Method to Modify the Characteristics and Corrosion Behavior of 304
      Stainless Steel by Surface Nanostructuring toward Biomedical Applications.
AB  - The study addresses how surface nanostructuring of AISI 304 stainless steel (SS)
      by surface mechanical attrition treatment (SMAT) influences its characteristic
      properties and corrosion behavior in Ringer's solution. SMAT of 304 SS induced
      plastic deformation, enabled surface nanocrystallization, refined the grain size,
      transformed the austenite phase to strain induced alpha'-martensite phase,
      increased the surface roughness, induced defects/dislocations, imparted
      compressive residual stresses at the surface, decreased the contact angle, and
      increased surface energy. The change in properties of 304 SS following treatment
      using 5 and 8 mm ? balls for 15, 30, 45, and 60 min has caused a deleterious
      influence on its corrosion resistance in Ringer's solution, while an improvement
      in corrosion behavior is observed for those treated using 2 mm ? balls. The
      increase in surface roughness, transformation of the austenite to alpha'
      martensite phase, a higher extent of deformation, and the presence of larger
      number of defects/dislocations are main factors responsible for the lower
      corrosion resistance observed for 304 SS treated using 5 and 8 mm ? balls in
      Ringer's solution. In spite of having these attributes with a relatively lower
      extent, 304 SS treated using 2 mm ? balls offered a better corrosion resistance
      and exhibits a better passivity. For those treated using 2 mm ? balls, the
      ability of the nanocrystalline surface to promote passivation outweighs the
      deleterious influences caused by the limited amount of deformation and
      defects/dislocations. Based on the findings of this study, it is recommend that
      SMAT of 304 SS using 2 mm ? balls for 15-30 min is the optimum condition to
      achieve the suitable surface profile, surface characteristics with better
      corrosion resistance. 

PMID- 26196216
TI  - Prevalence of Hepatitis E Virus Infection in Pigs at the Time of Slaughter,
      United Kingdom, 2013.
AB  - Since 2010, reports of infection with hepatitis E virus (HEV) have increased in
      England and Wales. Despite mounting evidence regarding the zoonotic potential of
      porcine HEV, there are limited data on its prevalence in pigs in the United
      Kingdom. We investigated antibody prevalence, active infection, and virus
      variation in serum and cecal content samples from 629 pigs at slaughter.
      Prevalence of antibodies to HEV was 92.8% (584/629), and HEV RNA was detected in
      15% of cecal contents (93/629), 3% of plasma samples (22/629), and 2% of both
      (14/629). However, although HEV is prevalent in pigs in the United Kingdom and
      viremic pigs are entering the food chain, most (22/23) viral sequences clustered
      separately from the dominant type seen in humans. Thus, pigs raised in the United
      Kingdom are unlikely to be the main source of human HEV infections in the United
      Kingdom. Further research is needed to identify the source of these infections. 

PMID- 26196219
TI  - Urban Particulate Matter-Activated Human Dendritic Cells Induce the Expansion of
      Potent Inflammatory Th1, Th2, and Th17 Effector Cells.
AB  - Exposure to urban particulate matter (UPM) exacerbates asthmatic lung
      inflammation. Lung dendritic cells (DCs) are critical for stimulating T cell
      immunity and in maintaining airway tolerance, but they also react to airway UPM.
      The adjuvant role of UPM in enhancing primary immune responses by naive cells to
      allergen has been reported, but the direct effects of UPM-activated DCs on the
      functionality of human memory CD4 T cells (Tms), which constitute the majority of
      T cells in the lung, has not been investigated. Blood CD1c(+) DCs were purified
      and activated with UPM in the presence or absence of house dust mite or tetanus
      toxoid control antigen. 5-(and -6)-Carboxyfluorescein diacetate succinimidyl
      ester-labeled blood Tms were cocultured with autologous DCs, T cell proliferation
      and effector function were assessed using flow cytometry, and secreted cytokines
      were measured by combined bead array. UPM-DCs elicited IFN-gamma and IL-13
      secretion and induced proliferation in Tms isolated from both allergic patients
      with asthma and healthy control subjects, whereas only IL-13 was produced by Tms
      from patients with atopic asthma stimulated by house dust mite-loaded DCs. UPM
      DCs drove the expansion and differentiation of a mixed population of Th1, Th2,
      and Th17 cell effectors through a mechanism that was dependent on major
      histocompatibility class II but not on cytokine-driven expansion. The data
      suggest that UPM not only has adjuvant properties but is also a source of antigen
      that stimulates the generation of Th2, Th1, and Th17 effector phenotypes, which
      have been implicated in both exacerbations of asthma and chronic inflammatory
      diseases. 

PMID- 26196220
TI  - Challenging conventional risk assessment with respect to human exposure to
      multiple food contaminants in food: A case study using maize.
AB  - Mycotoxins and heavy metals are ubiquitous in the environment and contaminate
      many foods. The widespread use of pesticides in crop production to control
      disease contributes further to the chemical contamination of foods. Thus multiple
      chemical contaminants threaten the safety of many food commodities; hence the
      present study used maize as a model crop to identify the severity in terms of
      human exposure when multiple contaminants are present. High Content Analysis
      (HCA) measuring multiple endpoints was used to determine cytotoxicity of complex
      mixtures of mycotoxins, heavy metals and pesticides. Endpoints included nuclear
      intensity (NI), nuclear area (NA), plasma membrane permeability (PMP),
      mitochondrial membrane potential (MMP) and mitochondrial mass (MM). At
      concentrations representing legal limits of each individual contaminant in maize
      (3ng/ml ochratoxin A (OTA), 1MUg/ml fumonisin B1 (FB1), 2ng/ml aflatoxin B1
      (AFB1), 100ng/ml cadmium (Cd), 150ng/ml arsenic (As), 50ng/ml chlorpyrifos (CP)
      and 5MUg/ml pirimiphos methyl (PM), the mixtures (tertiary mycotoxins plus Cd/As)
      and (tertiary mycotoxins plus Cd/As/CP/PM) were cytotoxic for NA and MM endpoints
      with a difference of up to 13.6% (p<=0.0001) and 12% (p<=0.0001) respectively
      from control values. The most cytotoxic mixture was (tertiary mycotoxins plus
      Cd/As/CP/PM) across all 4 endpoints (NA, NI, MM and MMP) with increases up to
      61.3%, 23.0%, 61.4% and 36.3% (p<=0.0001) respectively. Synergy was evident for
      two endpoints (NI and MM) at concentrations contaminating maize above legal
      limits, with differences between expected and measured values of (6.2-12.4%
      (p<=0.05-p<=0.001) and 4.5-12.3% (p<=0.05-p<=0.001) for NI and MM, respectively.
      The study introduces for the first time, a holistic approach to identify the
      impact in terms of toxicity to humans when multiple chemical contaminants are
      present in foodstuffs. Governmental regulatory bodies must begin to contemplate
      how to safeguard the population when such mixtures of contaminants are found in
      foods and this study starts to address this critical issue. 

PMID- 26196221
TI  - Environmental pollutants parathion, paraquat and bisphenol A show distinct
      effects towards nuclear receptors-mediated induction of xenobiotics-metabolizing
      cytochromes P450 in human hepatocytes.
AB  - Environmental pollutants parathion, bisphenol A and paraquat were not
      systematically studied towards the effects on the expression of phase I
      xenobiotics-metabolizing cytochromes P450 (CYPs). We monitored their effects on
      the expression of selected CYPs in primary cultures of human hepatocytes.
      Moreover, we investigated their effects on the receptors regulating these CYPs,
      particularly arylhydrocarbon receptor (AhR), pregnane X receptor (PXR) and
      glucocorticoid receptor (GR) by gene reporter assays. We found that parathion and
      bisphenol A are the activators of AhR. Moreover, they are the inducers of CYP1A1
      mRNA in hepatoma cells HepG2 as well as in human hepatocytes by AhR-dependent
      mechanism via formation of AhR-DNA-binding complex, as revealed by gel shift
      assay. All three compounds possessed anti-glucocorticoid action as revealed by GR
      dependent gene reporter assay and a decline in tyrosine aminotransferase (TAT)
      gene expression in human hepatocytes. Moreover, parathion and bisphenol A are the
      activators of PXR and inducers of CYP3A4 mRNA and protein in the primary cultures
      of human hepatocytes. In conclusion, the studied compounds displayed distinct
      activities towards nuclear receptors involved in many biological processes and
      these findings may help us to better understand their adverse actions in
      pathological states followed after their exposure. 

PMID- 26196222
TI  - Emerging antibody-based therapeutic strategies for bladder cancer: A systematic
      review.
AB  - Bladder cancer is the most common malignancy of the urinary tract, presents the
      highest recurrence rate among solid tumors and is the second leading cause of
      death in genitourinary cancers. Despite recent advances in understanding of
      pathophysiology of the disease, the management of bladder cancer patients remains
      a clinically challenging problem. Particularly, bladder tumors invading the
      muscularis propria and disseminated disease are often not responsive to currently
      available therapeutic approaches, which include surgery and conventional
      chemotherapy. Antibody-based therapeutic strategies have become an established
      treatment option for over a decade in several types of cancer. However, bladder
      cancer has remained mostly an "orphan disease" regarding the introduction of
      these novel therapeutics, which has been translated in few improvements in
      patients overall survival. In order to shift this paradigm, several clinical
      studies involving antibody-based therapeutic strategies targeting the most
      prominent bladder cancer-related biomolecular pathways and immunological
      mediators are ongoing. This systematic review explores antibody-based
      therapeutics for bladder cancer undergoing clinical trial and discusses the
      future perspectives in this field, envisaging the development of more effective
      guided therapeutics. 

PMID- 26196223
TI  - Characterization of MoS2-Graphene Composites for High-Performance Coin Cell
      Supercapacitors.
AB  - Two-dimensional materials, such as graphene and molybdenum disulfide (MoS2), can
      greatly increase the performance of electrochemical energy storage devices
      because of the combination of high surface area and electrical conductivity.
      Here, we have investigated the performance of solution exfoliated MoS2 thin
      flexible membranes as supercapacitor electrodes in a symmetrical coin cell
      arrangement using an aqueous electrolyte (Na2SO4). By adding highly conductive
      graphene to form nanocomposite membranes, it was possible to increase the
      specific capacitance by reducing the resistivity of the electrode and altering
      the morphology of the membrane. With continued charge/discharge cycles the
      performance of the membranes was found to increase significantly (up to 800%),
      because of partial re-exfoliation of the layered material with continued ion
      intercalation, as well as increasing the specific capacitance through
      intercalation pseudocapacitance. These results demonstrate a simple and scalable
      application of layered 2D materials toward electrochemical energy storage. 

PMID- 26196224
TI  - Underrecognition of Dengue during 2013 Epidemic in Luanda, Angola.
AB  - During the 2013 dengue epidemic in Luanda, Angola, 811 dengue rapid diagnostic
      test-positive cases were reported to the Ministry of Health. To better understand
      the magnitude of the epidemic and identify risk factors for dengue virus (DENV)
      infection, we conducted cluster surveys around households of case-patients and
      randomly selected households 6 weeks after the peak of the epidemic. Of 173 case
      cluster participants, 16 (9%) exhibited evidence of recent DENV infection. Of 247
      random cluster participants, 25 (10%) had evidence of recent DENV infection. Of
      13 recently infected participants who had a recent febrile illness, 7 (54%) had
      sought medical care, and 1 (14%) was hospitalized with symptoms consistent with
      severe dengue; however, none received a diagnosis of dengue. Behavior associated
      with protection from DENV infection included recent use of mosquito repellent or
      a bed net. These findings suggest that the 2013 dengue epidemic was larger than
      indicated by passive surveillance data. 

PMID- 26196225
TI  - Ambrisentan for the treatment of adults with pulmonary arterial hypertension: a
      review.
AB  - OBJECTIVE: To provide an overview of the drug profile of the orally active,
      selective endothelin A receptor antagonist ambrisentan, and its efficacy and
      safety in the treatment of patients with pulmonary arterial hypertension (PAH).
      RESEARCH DESIGN AND METHODS: Medical literature on the use of ambrisentan in PAH
      was identified using MEDLINE and EMBASE. Additional references were identified
      from the reference lists of published articles and from the authors' own
      bibliographies. RESULTS: Significant improvements in exercise capacity were
      observed with approved dosages of ambrisentan (5 or 10 mg once daily) in the AMB
      220 dose-ranging study and the pivotal ARIES-1 and ARIES-2 trials, with sustained
      effects up to 2 years observed in ARIES-E. Improvements in cardiopulmonary
      hemodynamic variables were reported in AMB-220 and ARIES-E (subset analysis).
      Ambrisentan had little or no effect on hepatic transporters in in vitro studies
      and displayed a low risk of potential drug-drug interactions, including those
      with other PAH therapies. Results from the VOLT post-marketing program confirmed
      the safety profile of ambrisentan observed in the ARIES studies, including the
      low incidence of liver function test abnormalities. Peripheral edema and anemia
      were common side effects of endothelin receptor antagonist therapies, including
      ambrisentan. In the recently completed AMBITION study (ClinicalTrials.gov
      Identifier: NCT01178073), upfront initial combination therapy with ambrisentan
      and tadalafil significantly reduced the risk of clinical failure (primary
      endpoint) by 50% compared with the pooled monotherapy groups. CONCLUSIONS: The
      long-term efficacy and safety profile of ambrisentan in patients with PAH is
      supported by data from a comprehensive clinical trial program and real-life, post
      marketing observations.

PMID- 26196226
TI  - The dynamic relationship between current and previous severe hypoglycemic events:
      a lagged dependent variable analysis among patients with type 2 diabetes who have
      initiated basal insulin.
AB  - BACKGROUND AND OBJECTIVE: Past studies have found episodes of severe hypoglycemia
      (SH) to be serially dependent. Those studies, however, only considered the impact
      of a single (index) event on future risk; few have analyzed SH risk as it evolves
      over time in the presence (or absence) of continuing events. The objective of
      this study was to determine the dynamic risks of SH events conditional on
      preceding SH events among patients with type 2 diabetes (T2D) who have initiated
      basal insulin. METHODS: We used an electronic health records database from the
      United States that included encounter and laboratory data and clinical notes on
      T2D patients who initiated basal insulin therapy between 2008 and 2011 and to
      identify SH events. We used a repeated-measures lagged dependent variable
      logistic regression model to estimate the impact of SH in one quarter on the risk
      of SH in the next quarter. RESULTS: We identified 7235 patients with T2D who
      initiated basal insulin. Patients who experienced >=1 SH event during any quarter
      were more likely to have >=1 SH event during the subsequent quarter than those
      who did not (predicted probabilities of 7.4% and 1.0%, respectively; p < 0.01).
      This effect was stronger than the impact of history of SH before starting basal
      insulin (predicted probabilities of 1.0% and 3.2%, respectively; p < 0.01) or of
      a history of SH during the titration period (predicted probabilities of 1.1% and
      2.8%, respectively; p < 0.01). CONCLUSIONS: The risk of experiencing a SH event
      is highly dependent on a patient's immediate history of SH events and therefore
      the value of preventing one SH event may be substantial. These results can inform
      patient care by providing clinicians with dynamic data on a patient's risk of SH,
      which in turn can facilitate appropriate adjustment of the risk-benefit ratio for
      individualized patient care. These results should, however, be interpreted in
      light of the key limitations of our study: not all SH events may have been
      captured or coded in the database, data on filled prescriptions were not
      available, we were unable to adjust for basal insulin dose, and the post
      titration follow-up period could have divided into time units other than quarters
      (3 month blocks) resulting in potentially different conclusions. Further real
      world studies on how to best to identify patients at risk for SH events based on
      the presence of recent SH events, rather than on more distant 'prior' events, can
      help healthcare providers to better manage patients starting basal insulin.

PMID- 26196227
TI  - An optimized protocol for expression and purification of murine perforin in
      insect cells.
AB  - Perforin (PFN) is one of the most important protein effectors of the immune
      system. It is produced by cytotoxic T lymphocytes and natural killer cells and
      helps with the clearance of virus-infected and tumor cells. PFN is a pore-forming
      protein that readily binds to the lipid membranes of target cells, oligomerizes
      at the cell surface and forms transmembrane pores that allow passage of ions and
      other larger molecules. Its characterization was hindered in the past by a lack
      of efficient and reliable expression systems that would result in pure and
      functional product. In this paper we present optimization of PFN expression in a
      baculovirus expression system. We optimized several parameters of murine PFN
      (mPFN) expression and purification and showed that the expressed product is pure
      and hemolytically active and that it forms pores in the plasma membranes of K562
      cells. We could also observe circular pores formed on liposome membranes by cryo
      electron microscopy (cryo-EM). Our protocol opens the door for further
      biochemical and biophysical assessment of PFN properties and interactions with
      small ligands and lipid membranes. 

PMID- 26196228
TI  - Zinc finger protein binding to DNA: an energy perspective using molecular
      dynamics simulation and free energy calculations on mutants of both zinc finger
      domains and their specific DNA bases.
AB  - Energy calculations based on MM-GBSA were employed to study various zinc finger
      protein (ZF) motifs binding to DNA. Mutants of both the DNA bound to their
      specific amino acids were studied. Calculated energies gave evidence for a
      relationship between binding energy and affinity of ZF motifs to their sites on
      DNA. DeltaG values were -15.82(12), -3.66(12), and -12.14(11.6) kcal/mol for
      finger one, finger two, and finger three, respectively. The mutations in the DNA
      bases reduced the value of the negative energies of binding (maximum value for
      DeltaDeltaG = 42Kcal/mol for F1 when GCG mutated to GGG, and DeltaDeltaG = 22
      kcal/mol for F2, the loss in total energy of binding originated in the loss in
      electrostatic energies upon mutation (r = .98). The mutations in key amino acids
      in the ZF motif in positions-1, 2, 3, and 6 showed reduced binding energies to
      DNA with correlation coefficients between total free energy and electrostatic was
      .99 and with Van der Waal was .93. Results agree with experimentally found
      selectivity which showed that Arginine in position-1 is specific to G, while
      Aspartic acid (D) in position 2 plays a complicated role in binding. There is a
      correlation between the MD calculated free energies of binding and those obtained
      experimentally for prepared ZF motifs bound to triplet bases in other reports (),
      our results may help in the design of ZF motifs based on the established
      recognition codes based on energies and contributing energies to the total
      energy. 

PMID- 26196229
TI  - Dual partitioning and attachment effects of rhamnolipid on pyrene biodegradation
      under bioavailability restrictions.
AB  - We investigated the effects of different bioavailability scenarios on the
      rhamnolipid-enhanced biodegradation of pyrene by the representative polycyclic
      aromatic hydrocarbon degrader Mycobacterium gilvum VM552. This biosurfactant
      enhanced biodegradation when pyrene was provided in the form of solid crystals;
      no effect was observed when the same amount of the chemical was preloaded on
      polydimethylsiloxane (PDMS). An enhanced effect was observed when pyrene was
      sorbed into soil but not with the dissolved compound. Synchronous fluorescence
      spectrophotometry and liquid scintillation were used to determine the phase
      exchange of pyrene. We also investigated the phase distribution of bacteria. Our
      results suggest that the rhamnolipid can enhance the biodegradation of pyrene by
      micellar solubilization and increase diffusive uptake. These mechanisms increase
      substrate acquisition by bacterial cells at exposure concentrations well above
      the half-saturation constant for active uptake. The moderate solubilization of
      pyrene from PDMS by the rhamnolipid and the prevention of cell attachment may
      explain the lack of enhancement for pyrene-preloaded PDMS.

PMID- 26196230
TI  - Persistent, circulative transmission of begomoviruses by whitefly vectors.
AB  - Begomoviruses comprise an emerging and economically important group of plant
      viruses exclusively transmitted by the sweetpotato whitefly Bemisia tabaci in
      many regions of the world. The past twenty years have witnessed significant
      progress in studying the molecular interactions between members of this virus
      group and B. tabaci. Mechanisms and proteins encoded by the insect vector and its
      bacterial symbionts, which have been shown to be important for virus
      transmission, have been identified and thoroughly studied. Despite the economic
      importance of this group of viruses and their impact on the global agriculture,
      progress in investigating the virus-vector interactions is moving slowly when
      compared with similar virus-vector systems in plants and animals. Major advances
      in this field and future perspectives will be discussed in this review. 

PMID- 26196231
TI  - Complementation of the human adenovirus type 5 VA RNAI defect by the Vaccinia
      virus E3L protein and serotype-specific VA RNAIs.
AB  - Human adenoviruses (HAdVs) encode for multifunctional non-coding virus-associated
      (VA) RNAs, which function as powerful suppressors of the cellular interferon
      (IFN) and RNA interference (RNAi) systems. In this study we tested the ability of
      various plant and animal virus encoded RNAi and IFN suppressor proteins to
      functionally substitute for the HAdV-5 VA RNAI. Our results revealed that only
      the Vaccinia virus (VACV) E3L protein was able to substitute for the HAdV-5 VA
      RNAI functions in virus-infected cells. Interestingly, the E3L protein rescues
      the translational defect but does not stimulate viral capsid mRNA accumulation
      observed with VA RNA. We further show that the E3L C-terminal region containing
      the dsRNA-binding domain is needed to enhance VA RNAI mutant virus replication.
      Additionally, we show that the HAdV-4 and HAdV-37 VA RNAI are more effective than
      the HAdV-5 VA RNAI in rescuing virus replication. 

PMID- 26196232
TI  - Innate and adaptive cellular phenotypes contributing to pulmonary disease in mice
      after respiratory syncytial virus immunization and infection.
AB  - Respiratory syncytial virus (RSV) is the major leading cause of infantile viral
      bronchiolitis. However, cellular phenotypes contributing to the RSV protection
      and vaccine-enhanced disease remain largely unknown. Upon RSV challenge, we
      analyzed phenotypes and cellularity in the lung of mice that were naive,
      immunized with formalin inactivated RSV (FI-RSV), or re-infected with RSV. In
      comparison with naive and live RSV re-infected mice, the high levels of
      eosinophils, neutrophils, plasmacytoid and CD11b(+) dendritic cells, and IL-4(+)
      CD4(+) T cells were found to be contributing to pulmonary inflammation in FI-RSV
      immune mice despite lung viral clearance. Alveolar macrophages appeared to play
      differential roles in protection and inflammation upon RSV infection of different
      RSV immune mice. These results suggest that multiple innate and adaptive immune
      components differentially contribute to RSV disease and inflammation. 

PMID- 26196233
TI  - Antimullerian hormone: prediction of cumulative live birth in gonadotropin
      releasing hormone antagonist treatment for in vitro fertilization.
AB  - OBJECTIVE: To assess the accuracy of antimullerian hormone (AMH) in predicting
      cumulative live birth rate (CLBR) within 1 year after treatment initiation in
      GnRH antagonist treatment cycles for in vitro fertilization (IVF). DESIGN:
      Observational (retrospective) substudy as part of an ongoing prospective cohort
      study. SETTING: University medical center. PATIENT(S): A total of 487 patients
      scheduled for IVF/intracytoplasmic sperm injection (ICSI). INTERVENTION(S):
      Patients starting their first IVF/ICSI cycle with 150 or 225 IU recombinant FSH
      and GnRH antagonist cotreatment were included. Serum samples collected before the
      first IVF treatment were used to determine AMH. Treatment data after treatment
      initiation for a maximum of 1 year were recorded. MAIN OUTCOME MEASURE(S):
      Prediction of CLBR with the use of AMH. RESULT(S): The model for predicting CLBR
      within 1 year included age at first treatment, AMH, type of infertility, and
      previous assisted reproductive technology treatment leading to live birth. The
      accuracy in discriminating between women who did or did not achieve a live birth
      was only 59%. AMH had intermediate added value in the prediction of CLBR as
      demonstrated by the net reclassification improvement (total 29.8). A nomogram
      based on age and AMH was developed by which a subgroup of patients could be
      identified with the poorest pregnancy prospects. CONCLUSION(S): The predictive
      accuracy of AMH for 1-year CLBR in GnRH antagonist treatment cycles was limited
      and did not yield much additional value on top of age. Withholding treatment
      based on predictors such as age and AMH, or a combination, remains problematic.
      CLINICAL TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov, NCT02309073.

PMID- 26196234
TI  - New strategy for diagnosing embryo implantation potential by combining proteomics
      and time-lapse technologies.
AB  - OBJECTIVE: To develop a diagnostic tool for embryo implantation potential with
      the use of proteomic fingerprinting combined with time-lapse morphokinetic
      analysis. DESIGN: Retrospective cohort study. SETTING: University-affiliated
      private in vitro fertilization center. PATIENT(S): Seventeen infertile patients
      undergoing intracytoplasmic sperm injection (ICSI) from our ovum donation
      program. INTERVENTION(S): No patient intervention. We examined morphokinetic data
      and proteomic data from the spent media of 16 embryos that implanted and 12
      embryos that did not implant. MAIN OUTCOME MEASURE(S): We analyzed seven proteins
      in the embryo spent media-SCF, TNFR1, PIGF-1, IFN-alpha2, IL-6, CXCL13, and GM
      CSF-with the use of a bead-based multiplexing technology and combined this data
      with the exact timing (in hours) of cell cycle duration (cc2), blastomere
      synchrony (s2), and 5-blastomere cleavage (t5) with the use of an incubator
      equipped with time-lapse videography. RESULT(S): Logistic regression analysis
      with the use of the forward-step likelihood selection method revealed that the
      presence/absence of interleukin (IL) 6 and the duration of cc2 were the most
      relevant embryo features for embryo selection. We combined these two parameters
      to obtain a hierarchic model that established four categories (A/B/C/D), based on
      the presence of IL-6 and a cc2 range of 5-12 hours. A direct relationship was
      observed between the morphologic categories and implantation rates: Those with
      the presence of IL-6 and 5-12 h cc2 had significantly higher implantation rates.
      CONCLUSION(S): The strategy we report here combines time-lapse and proteome
      analysis to improve embryo selection while minimizing handling and monitoring by
      the embryologist. Our results describe the utility of a combined
      biochemical/morphokinetic approach to select embryos for transfer according to
      their implantation potential. Clinical validation with larger sample sizes is
      mandatory to confirm the effectiveness of this initial study.

PMID- 26196235
TI  - Genome of Emerging Norovirus GII.17, United States, 2014.
AB  - To determine whether the norovirus strain GII.17 recently detected in Maryland,
      USA, (Hu/GII.17/Gaithersburg/2014/US) is spreading globally, we characterized the
      genome. High similarity with the norovirus GII.17 that caused recent outbreaks in
      Asia indicates that the same strain was present in the United States during the
      2014-15 norovirus season (winter). 

PMID- 26196236
TI  - Emerging therapeutic options for Waldenstrom macroglobulinemia/lymphoplasmacytic
      lymphoma.
AB  - Lymphoplasmacytic lymphoma is an indolent B-cell, non-Hodgkin lymphoma (NHL), the
      majority of which are characterized by production of a monoclonal immunoglobulin
      M (IgM) protein and are known as Waldenstrom macroglobulinemia. Identification of
      highly recurrent activating somatic mutation in MYD88 has improved our
      understanding of the pathogenesis of Waldenstrom macroglobulinemia and has
      therapeutic implications. Here, we review novel therapeutic agents in Waldenstrom
      macroglobulinemia/lymphoplasmacytic lymphoma, which have emerged in the past
      decade and discuss their comparative efficacy and safety, with emphasis on a
      Bruton's tyrosine kinase (BTK) inhibitor, which has been recently approved by the
      US FDA, specifically for Waldenstrom macroglobulinemia/lymphoplasmacytic
      lymphoma. Future research should focus on identifying targeted agents against
      activating mutations and long-term data for currently available novel agents
      should be critically evaluated, both in treatment-naive and in
      relapsed/refractory settings. 

PMID- 26196238
TI  - Cobra venom proteome and glycome determined from individual snakes of Naja atra
      reveal medically important dynamic range and systematic geographic variation.
AB  - Recent progress in snake venomics has shed much light on the intra-species
      variation among the toxins from different geographical regions and has provided
      important information for better snakebite management. Most previous reports on
      snake venomics were based on venoms pooled from different snakes. In this study,
      we present the proteomic and glycomic profiles of venoms from individual Naja
      atra snakes. The results reveal wide dynamic range of three-finger toxins.
      Systematic classification based on cardiotoxin (CTX-) profiles of A2/A4 and A6,
      respectively, allowed the identification of two putative subspecies of Taiwan
      cobra from the eastern and western regions. We also identified four major N
      glycan moieties on cobra snake venom metalloproteinase on the bi-antennary glycan
      core. ELISA showed that these glycoproteins (<3%) could elicit much higher
      antibody response in antiserum when compared to other high-abundance cobra venom
      toxins such as small molecular weight CTXs (~60%). By removing these high
      molecular weight glycoproteins from the immunogen, we demonstrated better
      protection than that achieved with conventional crude venom immunization in mice
      challenged by crude venom. We conclude that both intra-species and inter
      individual variations of proteomic and glycomic profiles of snake venomics should
      be considered to provide better antivenomic approach for snakebite management.
      BIOLOGICAL SIGNIFICANCE: Based on the proteomic and glycomic profiles of venoms
      obtained from individual snakes, we demonstrated a surprisingly wide dynamic
      range and geographical variation of three-finger toxins in cobra venomics. This
      provides a reasonable explanation for the variable neutralization effects of
      antivenom treatment on victims suffering from cobra snakebite and suggests a
      simple and economic method to produce potent antivenom with better efficacy.
      Since two major venomic profiles with distinct dynamic ranges were observed for
      Taiwan cobra venoms isolated from the eastern and western regions, the current
      venomic profile should be used as a quality control for future production of
      antivenom in clinical applications.

PMID- 26196237
TI  - ProteinInferencer: Confident protein identification and multiple experiment
      comparison for large scale proteomics projects.
AB  - Shotgun proteomics generates valuable information from large-scale and target
      protein characterizations, including protein expression, protein quantification,
      protein post-translational modifications (PTMs), protein localization, and
      protein-protein interactions. Typically, peptides derived from proteolytic
      digestion, rather than intact proteins, are analyzed by mass spectrometers
      because peptides are more readily separated, ionized and fragmented. The amino
      acid sequences of peptides can be interpreted by matching the observed tandem
      mass spectra to theoretical spectra derived from a protein sequence database.
      Identified peptides serve as surrogates for their proteins and are often used to
      establish what proteins were present in the original mixture and to quantify
      protein abundance. Two major issues exist for assigning peptides to their
      originating protein. The first issue is maintaining a desired false discovery
      rate (FDR) when comparing or combining multiple large datasets generated by
      shotgun analysis and the second issue is properly assigning peptides to proteins
      when homologous proteins are present in the database. Herein we demonstrate a new
      computational tool, ProteinInferencer, which can be used for protein inference
      with both small- or large-scale data sets to produce a well-controlled protein
      FDR. In addition, ProteinInferencer introduces confidence scoring for individual
      proteins, which makes protein identifications evaluable. This article is part of
      a Special Issue entitled: Computational Proteomics. 

PMID- 26196239
TI  - Impairment of the cortisol stress response mediated by the hypothalamus-pituitary
      interrenal (HPI) axis in zebrafish (Danio rerio) exposed to monocrotophos
      pesticide.
AB  - In teleosts, an important component of the stress response is coordinated by the
      hypothalamic-pituitary-interrenal (HPI) axis. Environmental contaminants might
      disrupt the stress axis and consequently affect the stress response in fish. To
      investigate the effect of monocrotophos (MCP) pesticide on the stress response of
      fish and its potential mechanisms, adult zebrafish (Danio rerio) were exposed to
      0, 1, 10, and 100MUg/L of a 40% MCP-based pesticide for 21d, after which time
      fish were subjected to a 3-min air-exposure stressor. Concentrations of the whole
      body cortisol were measured by radioimmunoassay and abundances of transcripts of
      proteins involved in the HPI axis were determined using quantitative real-time
      PCR. Results showed that 100MUg/L of MCP pesticide decreased whole-body cortisol
      levels of female zebrafish in response to an acute stressor, but without any
      effect on the cortisol response in males. 100MUg/L MCP pesticide reduced POMC and
      GR expression in the brain, MC2R and P45011beta expression in the head kidney,
      but enhanced 20beta-HSD2 expression in the head kidney, suggesting that MCP
      damaged the HPI axis involving acting at pituitary regulatory levels, inhibiting
      cortisol synthesis and stimulating cortisol catabolism, or disturbing the
      negative feedback regulation. Additionally, MCP depressed liver GR transcription
      but did not affect phosphoenolpyruvate carboxykinase and tyrosine
      aminotransferase expression in zebrafish, suggesting a role for this pesticide in
      reducing target tissue responsiveness to cortisol. Considered together, the
      reduced ability to elevate cortisol levels in response to an acute stress may be
      an endocrine dysfunction occurring in zebrafish subchronically exposed to MCP
      pesticide. 

PMID- 26196240
TI  - Contemporary Population-Based Comparison of Localized Ductal Adenocarcinoma and
      High-Risk Acinar Adenocarcinoma of the Prostate.
AB  - OBJECTIVE: To compare pathological characteristics, treatment patterns, and
      survival in patients with ductal adenocarcinoma (DC) compared to those with
      acinar adenocarcinoma (AC). MATERIALS AND METHODS: Using the National Cancer
      Database, we identified patients diagnosed with clinically localized (cN0, cM0)
      pure DC (n = 1328) and AC (n = 751,635) between 1998 and 2011. High-risk AC was
      defined as Gleason 8-10. Demographic, treatment, pathological, and survival
      characteristics of patients were compared. RESULTS: Compared to patients with
      Gleason 8-10 AC, those with DC presented with lower mean prostate-specific
      antigen (10.3 vs 16.2 ng/mL, P <.001), had similar rates (11.7% vs 11.5%, P = .8)
      of clinical extra-capsular extension (stage >= cT3), and were more likely to
      undergo prostatectomy (54% vs 36%, P <.001). Compared to patients with Gleason 8
      10 AC undergoing prostatectomy, those with DC had more favorable pathology: stage
      >= T3 (39% vs 52%, P <.001), fewer positive lymph nodes (4% vs 11%, P <.001), and
      fewer positive margins (25% vs 33%, P <.001). On Kaplan-Meier analysis, patients
      with DC had similar 5-year survival (75.0%, 95% confidence interval [CI] [71.7
      78.9]) compared to those with Gleason 8-10 AC (77.1%, 95% CI [76.6%-77.6%], P =
      .2). On Cox multivariable analysis, patients with Gleason 8-10 AC had a similar
      risk of death compared to those with DC (hazards ratio = 0.92, 95% CI [0.69
      1.23], P = 6). CONCLUSION: In this large contemporary population-based series,
      patients with DC of the prostate presented with lower prostate-specific antigen,
      had more favorable pathological features, and similar overall survival compared
      to men with Gleason 8-10 AC.

PMID- 26196241
TI  - Varicocele Negatively Affects Sperm Mitochondrial Respiration.
AB  - OBJECTIVE: To evaluate the effect of varicocele on oxidative stress, sperm
      mitochondrial respiratory efficiency, sperm morphology, and semen parameters.
      METHODS: A total of 20 patients with varicocele and 20 normozoospermic subjects
      without varicocele (control group) were recruited from a medical center for
      reproductive biology. The levels of serum reactive oxygen metabolites and seminal
      lipid peroxides were assessed for both control and varicocele subjects. Sperm
      deoxyribonucleic acid fragmentation was measured by sperm chromatin dispersion
      test. Mitochondrial respiratory activity was evaluated with a polarographic assay
      of oxygen consumption carried out in hypotonically treated sperm cells. RESULTS:
      In this study, varicocele patients were compared with men without varicoceles.
      Oxidative stress was observed in the serum and seminal fluid of varicocele
      patients. These patients showed an increase of 59% (P <.05) in serum reactive
      oxygen metabolites and a 3-fold increase in the level of sperm lipid peroxides. A
      parallel and significant increase (a 2-fold increase; P <.05) in the degree of
      sperm deoxyribonucleic acid fragmentation was also observed. Varicocele patients
      showed a 27% decrease (P <.05) in mitochondrial respiratory activity in
      comparison to the control group. A 32% increase (P <.05) in sperm midpiece
      defects and a 41% decrease (P <.05) in sperm concentration and motility were also
      observed. CONCLUSION: Men with varicocele have increased markers of oxidative
      stress and decreased mitochondrial respiratory activity. These results correlated
      with abnormalities in semen parameters. For morphology, these correlated with
      midpiece defects.

PMID- 26196242
TI  - Ultrastructural study of cultured ovine bone marrow-derived mesenchymal stromal
      cells.
AB  - Ovine bone marrow-derived mesenchymal stromal cells (oBM-MSCs) represent a good
      animal model for cell-based therapy and tissue engineering. Despite their use as
      a new therapeutic tool for several clinical applications, the morphological
      features of oBM-MSCs are yet unknown. Therefore, in this study the
      ultrastructural phenotype of these cells was analysed by transmission electron
      microscopy (TEM). The oBM-MSCs were isolated from the iliac crest and cultured
      until they reached near-confluence. After trypsinization, they were processed to
      investigate their ultrastructural features as well as specific surface marker
      proteins by flow cytometry and immunogold electron microscopy. Flow cytometry
      displayed that all oBM-MSCs lacked expression of CD31, CD34, CD45, HLA-DR whereas
      they expressed CD44, CD58, HLAI and a minor subset of the cell population (12%)
      exhibited CD90. TEM revealed the presence of two morphologically distinct cell
      types: cuboidal electron-lucent cells and spindle-shaped electron-dense cells,
      both expressing the CD90 antigen. Most of the electron-lucent cells showed
      glycogen aggregates, dilated cisternae of RER, moderately developed Golgi
      complex, and secretory activity. The electron-dense cell type was constituted by
      two different cell-populations: type A cells with numerous endosomes, dense
      bodies, rod-shaped mitochondria and filopodia; type B cells with elongated
      mitochondria, thin pseudopodia and cytoplasmic connectivity with electron-lucent
      cells. These morphological findings could provide a useful support to identify
      "in situ" the cellular components involved in the cell-therapy when cultured oBM
      MSCs are injected. 

PMID- 26196244
TI  - CEACAM1 regulates integrin alphaIIbbeta3-mediated functions in platelets.
AB  - Previous studies have implicated that the Ig-ITIM superfamily member, CEACAM1 may
      regulate integrin function. While CEACAM1 has been demonstrated to play a role as
      an inhibitory co-receptor of ITAM-associated GPVI/FcR gamma-chain signaling
      pathways in platelets, its physiologic role in integrin alphaIIbbeta3-mediated
      platelet function is unclear. In this study, we investigate the functional
      importance of Ceacam1 in murine platelets. We show that CEACAM1 is constitutively
      associated with integrin alphaIIbbeta3 in resting human and mouse platelets as
      demonstrated by co-immunoprecipitation studies. Using Ceacam1-deficient mice, we
      show that they have prolonged tail bleeding times and volume of blood lost that
      is corrected by reconstitution with platelet Ceacam1. Ceacam1(-/-) platelets have
      moderate integrin alphaIIbbeta3 mediated functional defects with impaired
      kinetics of platelet spreading on fibrinogen and failure to retract fibrin clots
      in vitro. This functional integrin alphaIIbbeta3 defect could not be attributed
      to altered integrin alphaIIbbeta3 expression. Ceacam1(-/-) platelets displayed
      normal "inside-out" signaling properties as demonstrated by normal agonist
      induced binding of soluble (fluorescein isothiocyanate) FITC-fibrinogen, JON/A
      antibody binding, and increases in cytosolic free calcium levels. This study
      provides direct evidence that Ceacam1 is essential for normal integrin
      alphaIIbbeta3-mediated platelet function and that disruption of mouse Ceacam1
      induced moderate integrin alphaIIbbeta3-mediated functional defects.

PMID- 26196243
TI  - Fertile fathoms: Deep reproductive refugia for threatened shallow corals.
AB  - The persistence of natural metapopulations may depend on subpopulations that
      exist at the edges of species ranges, removed from anthropogenic stress.
      Mesophotic coral ecosystems (30-150 m) are buffered from disturbance by depth and
      distance, and are potentially massive reservoirs of coral diversity and
      fecundity; yet we know little about the reproductive capabilities of their
      constituent species and the potential for these marginal environments to
      influence patterns of coral reef persistence. We investigated the reproductive
      performance of the threatened depth-generalist coral Orbicella faveolata over the
      extent of its vertical range to assess mesophotic contributions to regional
      larval pools. Over equal habitat area, mesophotic coral populations were found to
      produce over an order of magnitude more eggs than nearby shallow populations.
      Positive changes with depth in both population abundance and polyp fecundity
      contributed to this discrepancy. Relative larval pool contributions of deeper
      living corals will likely increase as shallow habitats further degrade due to
      climate change and local habitat degradation. This is a compelling example of the
      potential for marginal habitat to be critical to metapopulation persistence as
      reproductive refugia. 

PMID- 26196245
TI  - Antidepressant-like effect of quercetin in bulbectomized mice and involvement of
      the antioxidant defenses, and the glutamatergic and oxidonitrergic pathways.
AB  - Olfactory bulbectomy (OB) is an animal model of depression that can mimic
      symptoms that are characteristic of depressive patients, such as behavioral,
      neurochemical and neuromorphological changes. Quercetin decreased the immobility
      time in the forced swimming test and tail suspension test. With the open field
      test, quercetin did not alter the locomotor activity of mice and in the splash
      test, quercetin increased the time spent grooming. The repeated treatment with
      quercetin (25mg/kg, for 14days) reversed the behavioral hyperactivity induced by
      OB in the open field test and was able to prevent depressant-like effects in the
      forced swimming test and tail suspension test. Regarding oxidative stress, OB
      reduced the levels of glutathione and increase the activity of superoxide
      dismutase and lipid hydroperoxide content (LOOH) in the hippocampus. Only the
      increase in LOOH levels was reversed by treatment with quercetin. In a further
      series of experiments with non-bulbectomized mice, the antidepressant effect of
      quercetin in the tail suspension test was reversed by the pretreatment of mice
      with NMDA, l-arginine or sildenafil. The administration of methylene blue and 7
      nitroindazole, in combination with an underactive dose of quercetin (5mg/kg,
      p.o.), decreased the immobility time in the tail suspension test compared with
      the use of drug alone. There was no significant change in locomotor activity in
      the open field test. Our results suggest that the antidepressant effect of
      quercetin is dependent on the inhibition of the NMDA receptors and/or synthesis
      of nitric oxide. In addition, considering the reduction of LOOH levels on the
      hippocampus, we verify that the antioxidant effects of quercetin also contribute
      to its antidepressive potential. These data contribute to the understanding of
      the mechanisms involved in the antidepressant effect of quercetin and reinforce
      the involvement of the NMDA receptors and the nitric oxide on the pathophysiology
      of depression. 

PMID- 26196247
TI  - Label Propagation Prediction of Drug-Drug Interactions Based on Clinical Side
      Effects.
AB  - Drug-drug interaction (DDI) is an important topic for public health, and thus
      attracts attention from both academia and industry. Here we hypothesize that
      clinical side effects (SEs) provide a human phenotypic profile and can be
      translated into the development of computational models for predicting adverse
      DDIs. We propose an integrative label propagation framework to predict DDIs by
      integrating SEs extracted from package inserts of prescription drugs, SEs
      extracted from FDA Adverse Event Reporting System, and chemical structures from
      PubChem. Experimental results based on hold-out validation demonstrated the
      effectiveness of the proposed algorithm. In addition, the new algorithm also
      ranked drug information sources based on their contributions to the prediction,
      thus not only confirming that SEs are important features for DDI prediction but
      also paving the way for building more reliable DDI prediction models by
      prioritizing multiple data sources. By applying the proposed algorithm to 1,626
      small-molecule drugs which have one or more SE profiles, we obtained 145,068
      predicted DDIs. The predicted DDIs will help clinicians to avoid hazardous drug
      interactions in their prescriptions and will aid pharmaceutical companies to
      design large-scale clinical trial by assessing potentially hazardous drug
      combinations. All data sets and predicted DDIs are available at
      http://astro.temple.edu/~tua87106/ddi.html. 

PMID- 26196246
TI  - Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of
      nasopharyngeal carcinoma.
AB  - The expression of annexin A2 (ANXA2) in nasopharyngeal carcinoma (NPC) cells
      induces the immunosuppressive response in dendritic cells; however, the oncogenic
      effect and clinical significance of ANXA2 have not been fully investigated in NPC
      cells. Immunohistochemical staining for ANXA2 was performed in 61 patients and
      the association with clinicopathological status was determined. Short hairpin
      (sh)RNA knockdown of ANXA2 was used to examine cellular effects of ANXA2, by
      investigating alterations in cell proliferation, migration, invasion, adhesion,
      tube-formation assay, and chemo- and radiosensitivity assays were performed. RT
      qPCR, Western blotting, and immunofluorescence were applied to determine
      molecular expression levels. Clinical association studies showed that the
      expression of ANXA2 was significantly correlated with metastasis (p = 0.0326) and
      poor survival (p = 0.0256). Silencing of ANXA2 suppressed the abilities of cell
      proliferation, adhesion, migration, invasion, and vascular formation in NPC cell.
      ANXA2 up-regulated epithelial-mesenchymal transition associated signal proteins.
      Moreover, ANXA2 reduced sensitivities to irradiation and chemotherapeutic drugs.
      These results define ANXA2 as a novel prognostic factor for malignant processes,
      and it can serve as a molecular target of therapeutic interventions for NPC. 

PMID- 26196248
TI  - A novel quantitative assay of mitophagy: Combining high content fluorescence
      microscopy and mitochondrial DNA load to quantify mitophagy and identify novel
      pharmacological tools against pathogenic heteroplasmic mtDNA.
AB  - Mitophagy is a cellular mechanism for the recycling of mitochondrial fragments.
      This process is able to improve mitochondrial DNA (mtDNA) quality in
      heteroplasmic mtDNA disease, in which mutant mtDNA co-exists with normal mtDNA.
      In disorders where the load of mutant mtDNA determines disease severity it is
      likely to be an important determinant of disease progression. Measuring mitophagy
      is technically demanding. We used pharmacological modulators of autophagy to
      validate two techniques for quantifying mitophagy. First we used the IN Cell 1000
      analyzer to quantify mitochondrial co-localisation with LC3-II positive
      autophagosomes. Unlike conventional fluorescence and electron microscopy, this
      high-throughput system is sufficiently sensitive to detect transient low
      frequency autophagosomes. Secondly, because mitophagy preferentially removes
      pathogenic heteroplasmic mtDNA mutants, we developed a heteroplasmy assay based
      on loss of m.3243A>G mtDNA, during culture conditions requiring oxidative
      metabolism ("energetic stress"). The effects of the pharmacological modulators on
      these two measures were consistent, confirming that the high throughput imaging
      output (autophagosomes co-localising with mitochondria) reflects mitochondrial
      quality control. To further validate these methods, we performed a more detailed
      study using metformin, the most commonly prescribed antidiabetic drug that is
      still sometimes used in Maternally Inherited Diabetes and Deafness (MIDD). This
      confirmed our initial findings and revealed that metformin inhibits mitophagy at
      clinically relevant concentrations, suggesting that it may have novel therapeutic
      uses. 

PMID- 26196249
TI  - In vitro screening of clinical drugs identifies sensitizers of oncolytic viral
      therapy in glioblastoma stem-like cells.
AB  - Oncolytic viruses (OV) have broad potential as an adjuvant for the treatment of
      solid tumors. The present study addresses the feasibility of clinically
      applicable drugs to enhance the oncolytic potential of the OV Delta24-RGD in
      glioblastoma. In total, 446 drugs were screened for their viral sensitizing
      properties in glioblastoma stem-like cells (GSCs) in vitro. Validation was done
      for 10 drugs to determine synergy based on the Chou Talalay assay. Mechanistic
      studies were undertaken to assess viability, replication efficacy, viral
      infection enhancement and cell death pathway induction in a selected panel of
      drugs. Four viral sensitizers (fluphenazine, indirubin, lofepramine and
      ranolazine) were demonstrated to reproducibly synergize with Delta24-RGD in
      multiple assays. After validation, we underscored general applicability by
      testing candidate drugs in a broader context of a panel of different GSCs,
      various solid tumor models and multiple OVs. Overall, this study identified four
      viral sensitizers, which synergize with Delta24-RGD and two other strains of OVs.
      The viral sensitizers interact with infection, replication and cell death
      pathways to enhance efficacy of the OV. 

PMID- 26196250
TI  - Precision medicine for metastatic breast cancer--limitations and solutions.
AB  - The development of precision medicine for the management of metastatic breast
      cancer is an appealing concept; however, major scientific and logistical
      challenges hinder its implementation in the clinic. The identification of driver
      mutational events remains the biggest challenge, because, with the few exceptions
      of ER, HER2, PIK3CA and AKT1, no validated oncogenic drivers of breast cancer
      exist. The development of bioinformatic tools to help identify driver mutations,
      together with assessment of pathway activation and dependency should help resolve
      this issue in the future. The occurrence of secondary resistance, such as ESR1
      mutations, following endocrine therapy poses a further challenge. Ultra-deep
      sequencing and monitoring of circulating tumour DNA (ctDNA) could permit early
      detection of the genetic events underlying resistance and inform on combination
      therapy approaches. Beside these scientific challenges, logistical and
      operational issues are a major limitation to the development of precision
      medicine. For example, the low incidence of most candidate genomic alterations
      hinders randomized trials, as the number of patients to be screened would be too
      high. We discuss these limitations and the solutions, which include scaling-up
      the number of patients screened for identifying a genomic alteration, the
      clustering of genomic alterations into pathways, and the development of
      personalized medicine trials. 

PMID- 26196251
TI  - Breast cancer: oophorectomy for BRCA1 ER--negative disease-an open debate.

PMID- 26196253
TI  - ATP Hydrolysis in the RecA-DNA Filament Promotes Structural Changes at the
      Protein-DNA Interface.
AB  - To address the mechanistic roles of ATP hydrolysis in RecA-promoted strand
      exchange reaction in homologous recombination, quantum mechanical calculations
      are performed on key parts of the RecA-DNA complex. We find that ATP hydrolysis
      may induce changes at the protein-DNA interface, resulting in the rearrangement
      of the hydrogen bond network connecting the ATP and the DNA binding sites. 

PMID- 26196254
TI  - Pediatric Index of Cardiac Surgical Intensive Care Mortality Risk Score for
      Pediatric Cardiac Critical Care.
AB  - OBJECTIVE: Comparison of clinical outcomes is imperative in the evaluation of
      healthcare quality. Risk adjustment for children undergoing cardiac surgery poses
      unique challenges, due to its distinct nature. We developed a risk-adjustment
      tool specifically focused on critical care mortality for the pediatric cardiac
      surgical population: the Pediatric Index of Cardiac Surgical Intensive care
      Mortality score. DESIGN: Retrospective analysis of prospectively collected
      pediatric critical care data. SETTING: Pediatric critical care units in the
      United States. PATIENTS: Pediatric cardiac intensive care surgical patients.
      INTERVENTIONS: Prospectively collected data from consecutive patients admitted to
      ICUs were obtained from The Virtual PICU System (VPS, LLC, Los Angeles, CA), a
      national pediatric critical care database. Thirty-two candidate physiologic,
      demographic, and diagnostic variables were analyzed for inclusion in the
      development of the Pediatric Index of Cardiac Surgical Intensive care Mortality
      model. Multivariate logistic regression with stepwise selection was used to
      develop the model. MEASUREMENTS AND MAIN RESULTS: A total of 16,574 cardiac
      surgical patients from the 55 PICUs across the United States were included in the
      analysis. Thirteen variables remained in the final model, including the validated
      Society of Thoracic Surgeons-European Association of Cardio-Thoracic Surgery
      Congenital Heart Surgery Mortality (STAT) score and admission time with respect
      to cardiac surgery, which identifies whether the patient underwent the index
      surgical procedure before or after admission to the ICU. Pediatric Index of
      Cardiac Surgical Intensive Care Mortality (PICSIM) performance was compared with
      the performance of Pediatric Risk of Mortality-3 and Pediatric Index of Mortality
      2 risk of mortality scores, as well as the STAT score and STAT categories by
      calculating the area under the curve of the receiver operating characteristic
      from a validation dataset: PICSIM (area under the curve = 0.87) performed better
      than Pediatric Index of Mortality-2 (area under the curve = 0.81), Pediatric Risk
      of Mortality-3 (area under the curve = 0.82), STAT score (area under the curve =
      0.77), STAT category (area under the curve = 0.75), and Risk Adjustment for
      Congenital Heart Surgery-1 (area under the curve = 0.74). CONCLUSIONS: This newly
      developed mortality score, PICSIM, consisting of 13 risk variables encompassing
      physiology, cardiovascular condition, and time of admission to the ICU showed
      better discrimination than Pediatric Index of Mortality-2, Pediatric Risk of
      Mortality-3, and STAT score and category for mortality in a multisite cohort of
      pediatric cardiac surgical patients. The introduction of the variable "admission
      time with respect to cardiac surgery" allowed prediction of mortality when
      patients are admitted to the ICU either before or after the index surgical
      procedure.

PMID- 26196252
TI  - Cognitive effects of endocrine therapy for breast cancer: keep calm and carry on?
AB  - The number of breast cancer survivors is gradually increasing and a subset of
      these patients experience long-term adverse effects of adjuvant systemic therapy,
      including cognitive decline. Surprisingly, relatively little is known about the
      long-term adverse effects of endocrine treatment on cognition. As 75% of all
      patients with breast cancer are eligible to receive hormonal treatment,
      understanding the potential neurocognitive adverse effects of such therapy is of
      utmost importance. Concerns about adverse cognitive effects of adjuvant endocrine
      therapy are timely, as recently updated guidelines recommend increasing the
      length of such therapy from 5 years to 10 years for a subset of patients. The
      decline of cognitive functions can have a detrimental impact on quality of life
      and might interfere with independent living. This Review discusses the tissue
      selective side effects of endocrine therapies and specifically their impact on
      cognitive function, on the basis of clinical data; the neurobiological effects of
      endocrine therapies as observed in preclinical models are also discussed. We
      highlight the critical issues that need to be addressed in future preclinical and
      clinical studies in order to best assess the cognitive effects of endocrine
      treatment in patients with breast cancer. 

PMID- 26196255
TI  - An Approach to More Accurate Model Systems for Purple Acid Phosphatases (PAPs).
AB  - The active site of mammalian purple acid phosphatases (PAPs) have a dinuclear
      iron site in two accessible oxidation states (Fe(III)2 and Fe(III)Fe(II)), and
      the heterovalent is the active form, involved in the regulation of phosphate and
      phosphorylated metabolite levels in a wide range of organisms. Therefore, two
      sites with different coordination geometries to stabilize the heterovalent active
      form and, in addition, with hydrogen bond donors to enable the fixation of the
      substrate and release of the product, are believed to be required for
      catalytically competent model systems. Two ligands and their dinuclear iron
      complexes have been studied in detail. The solid-state structures and properties,
      studied by X-ray crystallography, magnetism, and Mossbauer spectroscopy, and the
      solution structural and electronic properties, investigated by mass spectrometry,
      electronic, nuclear magnetic resonance (NMR), electron paramagnetic resonance
      (EPR), and Mossbauer spectroscopies and electrochemistry, are discussed in detail
      in order to understand the structures and relative stabilities in solution. In
      particular, with one of the ligands, a heterovalent Fe(III)Fe(II) species has
      been produced by chemical oxidation of the Fe(II)2 precursor. The phosphatase
      reactivities of the complexes, in particular, also of the heterovalent complex,
      are reported. These studies include pH-dependent as well as substrate
      concentration dependent studies, leading to pH profiles, catalytic efficiencies
      and turnover numbers, and indicate that the heterovalent diiron complex discussed
      here is an accurate PAP model system. 

PMID- 26196256
TI  - Accurate ab initio calculations of O-HO and O-H(-)O proton chemical shifts:
      towards elucidation of the nature of the hydrogen bond and prediction of hydrogen
      bond distances.
AB  - The inability to determine precisely the location of labile protons in X-ray
      molecular structures has been a key barrier to progress in many areas of
      molecular sciences. We report an approach for predicting hydrogen bond distances
      beyond the limits of X-ray crystallography based on accurate ab initio
      calculations of O-HO proton chemical shifts, using a combination of DFT and
      contactor-like polarizable continuum model (PCM). Very good linear correlation
      between experimental and computed (at the GIAO/B3LYP/6-311++G(2d,p) level of
      theory) chemical shifts were obtained with a large set of 43 compounds in CHCl3
      exhibiting intramolecular O-HO and intermolecular and intramolecular ionic O-H(
      )O hydrogen bonds. The calculated OH chemical shifts exhibit a strong linear
      dependence on the computed (O)HO hydrogen bond length, in the region of 1.24 to
      1.85 A, of -19.8 ppm A(-1) and -20.49 ppm A(-1) with optimization of the
      structures at the M06-2X/6-31+G(d) and B3LYP/6-31+G(d) level of theory,
      respectively. A Natural Bond Orbitals (NBO) analysis demonstrates a very good
      linear correlation between the calculated (1)H chemical shifts and (i) the second
      order perturbation stabilization energies, corresponding to charge transfer
      between the oxygen lone pairs and sigma antibonding orbital and (ii) Wiberg bond
      order of the O-HO and O-H(-)O hydrogen bond. Accurate ab initio calculations of O
      HO and O-H(-)O (1)H chemical shifts can provide improved structural and
      electronic description of hydrogen bonding and a highly accurate measure of
      distances of short and strong hydrogen bonds. 

PMID- 26196258
TI  - Controllable Assembly of Hierarchical Macroporous-Mesoporous LnFeO3 and Their
      Catalytic Performance in the CO + NO Reaction.
AB  - A new synthesis strategy to prepare hierarchical macroporous-mesoporous materials
      employing poly(ethylene oxide)-poly(phenylene oxide)-poly(ethylene oxide) (PEO
      PPO-PEO) as a single template and an acid adjusting agent was reported. There is
      a hierarchical structure including macropores with a size of 50-100 nm and
      mesopores in the macroporous walls with a size of 3-5 nm. The macroporous walls
      are composed of rare earth orthoferrite nanoparticles with a size of 5-10 nm.
      These hierarchically porous materials show high catalytic activities for the CO +
      NO reaction, and NO can be fully converted to N2 at temperatures as low as 350 
      degrees C, indicating their potential in the catalytic conversion of automotive
      exhaust gas and other catalysis-related fields. This synthesis strategy is a
      facile method for the preparation of hierarchical porous materials and may give
      us a guideline for the synthesis of functional materials with further catalytic
      applications. 

PMID- 26196257
TI  - Diastereoselective, Zinc-Catalyzed Alkynylation of alpha-Bromo Oxocarbenium Ions.
AB  - We have developed a bromination/alkynylation sequence that enables efficient
      transformation of simple cyclic enol ethers to difunctionalized products. The
      success of this strategy relies on a highly diastereselective, zinc-catalyzed
      addition of terminal alkynes to alpha-bromo oxocarbenium ions, formed in situ via
      ionization of acetal precursors. Using this method, trans-alpha-alkynyl-beta-halo
      pyran and furan derivatives can be prepared with high diastereoselectivity and
      excellent functional group tolerance. 

PMID- 26196259
TI  - Long-Term Persistence of an Anxiolytic Drug (Oxazepam) in a Large Freshwater
      Lake.
AB  - Production and human consumption of pharmaceuticals result in contamination of
      surface waters worldwide. Little is known about the long-term (i.e., over
      decades) fate of pharmaceuticals in aquatic systems. Here, we show that the most
      prescribed anxiolytic in Sweden (oxazepam) persists in its therapeutic form for
      several decades after being deposited in a large freshwater lake. By comparing
      sediment cores collected in 1995 and 2013, we demonstrate that oxazepam inputs
      from the early 1970s remained in the sediments until sampling in 2013, despite in
      situ degradation processes and sediment diagenesis. In laboratory and pond
      experiments, we further reveal that therapeutic forms of oxazepam can persist
      over several months in cold (5  degrees C) lake water free from UV light. We
      conclude that oxazepam can persist in lakes over a time scale much longer than
      previously realized and that levels can build up in lakes due to both a legacy of
      past inputs and a growing urban population. 

PMID- 26196260
TI  - Therapy of caustic ingestion: new treatment considerations.
AB  - PURPOSE OF REVIEW: This review will focus on therapeutic considerations and
      recent advances in treatment of caustic ingestion injuries. RECENT FINDINGS: A
      retrospective study suggests that it may be safe to advance the endoscope beyond
      the first circumferential burn to allow for a more complete assessment of extent
      of injury. A randomized controlled prospective study suggested that a 3-day
      course of high-dose methylprednisolone might reduce the occurrence of esophageal
      stricture formation. Balloon dilatation has been shown to be as effective as
      other bougienage techniques with lower risk of perforations. Recent studies
      indicate that esophageal dilatation can be safely performed as early as 5-15 days
      after initial ingestion and may decrease risk for long-term stricture formation.
      The use of adjunctive treatment, such as topical mitomycin C and esophageal
      stents, shows promise in reducing the reoccurrence of stricture formation after
      dilatation. SUMMARY: Caustic ingestion remains a significant problem in children,
      despite continued efforts to educate the public about ways to avoid this
      preventable accident. Because there are few good quality therapeutic trials in
      children, many of the current recommendations regarding treatment are based on
      expert opinion. Large, prospective, multicenter, controlled treatment trials are
      needed to identify the best protocols to prevent serious complications.

PMID- 26196261
TI  - The pediatric heart network: meeting the challenges to multicenter studies in
      pediatric heart disease.
AB  - PURPOSE OF REVIEW: Because of the relatively small numbers of pediatric patients
      with congenital heart disease cared for in any individual center, there is a
      significant need for multicenter clinical studies to validate new medical or
      surgical therapies. The Pediatric Heart Network (PHN), with 15 years of
      experience in multicenter clinical research, has tackled numerous challenges when
      conducting multicenter studies. RECENT FINDINGS: This review describes the
      challenges encountered and the strategies employed to conduct high-quality,
      collaborative research in pediatric cardiovascular disease. SUMMARY: Sharing
      lessons learned from the PHN can provide guidance to investigators interested in
      conducting pediatric multicenter studies.

PMID- 26196262
TI  - Hepatitis C in children in times of change.
AB  - PURPOSE OF REVIEW: The global prevalence of hepatitis C infection is increasing.
      Here, hepatitis C infection in children is reviewed with the assumption that the
      new effective treatment will be available for treating children. RECENT FINDINGS:
      Recently, effective treatment for hepatitis C infection has become available for
      adults. Understanding of vertical transmission, how frequently it occurs, which
      maternal and fetal factors can influence risks is critical in creating these new
      strategies. The natural history of vertically acquired disease, especially the
      chance of spontaneous clearance as well as the incidents of rapid progression,
      needs to be considered in deciding when or if to treat a child. The advantages
      and drawbacks to delayed treatment (pathophysiologic, psychological, societal,
      financial) should be considered with respect to the individual child and in a
      broader context. SUMMARY: Although hepatitis C virus infection is not benign, it
      is usually very slowly progressive and is not easily transmitted through casual
      contact. With the expectation that effective treatment will soon be available to
      children, deferring treatment combined with cautious surveillance will optimize
      hepatitis C virus treatment for children.

PMID- 26196263
TI  - Mono-Mercury Doping of Au25 and the HOMO/LUMO Energies Evaluation Employing
      Differential Pulse Voltammetry.
AB  - Controlling the bimetal nanoparticle with atomic monodispersity is still
      challenging. Herein, a monodisperse bimetal nanoparticle is synthesized in 25%
      yield (on gold atom basis) by an unusual replacement method. The formula of the
      nanoparticle is determined to be Au24Hg1(PET)18 (PET: phenylethanethiolate) by
      high-resolution ESI-MS spectrometry in conjunction with multiple analyses
      including X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis
      (TGA). X-ray single-crystal diffraction reveals that the structure of
      Au24Hg1(PET)18 remains the structural framework of Au25(PET)18 with one of the
      outer-shell gold atoms replaced by one Hg atom, which is further supported by
      theoretical calculations and experimental results as well. Importantly,
      differential pulse voltammetry (DPV) is first employed to estimate the highest
      occupied molecular orbit (HOMO) and the lowest unoccupied molecular orbit (LUMO)
      energies of Au24Hg1(PET)18 based on previous calculations. 

PMID- 26196264
TI  - Estimates of Outbreak Risk from New Introductions of Ebola with Immediate and
      Delayed Transmission Control.
AB  - While the ongoing Ebola outbreak continues in the West Africa countries of
      Guinea, Sierra Leone, and Liberia, health officials elsewhere prepare for new
      introductions of Ebola from infected evacuees or travelers. We analyzed
      transmission data from patients (i.e., evacuees, international travelers, and
      those with locally acquired illness) in countries other than the 3 with
      continuing Ebola epidemics and quantitatively assessed the outbreak risk from new
      introductions by using different assumptions for transmission control (i.e.,
      immediate and delayed). Results showed that, even in countries that can quickly
      limit expected number of transmissions per case to <1, the probability that a
      single introduction will lead to a substantial number of transmissions is not
      negligible, particularly if transmission variability is high. Identifying
      incoming infected travelers before symptom onset can decrease worst-case outbreak
      sizes more than reducing transmissions from patients with locally acquired cases,
      but performing both actions can have a synergistic effect. 

PMID- 26196265
TI  - Non-adiabatic effects in thermochemistry, spectroscopy and kinetics: the general
      importance of all three Born-Oppenheimer breakdown corrections.
AB  - Using a simple model Hamiltonian, the three correction terms for Born-Oppenheimer
      (BO) breakdown, the adiabatic diagonal correction (DC), the first-derivative
      momentum non-adiabatic correction (FD), and the second-derivative kinetic-energy
      non-adiabatic correction (SD), are shown to all contribute to thermodynamic and
      spectroscopic properties as well as to thermal non-diabatic chemical reaction
      rates. While DC often accounts for >80% of thermodynamic and spectroscopic
      property changes, the commonly used practice of including only the FD correction
      in kinetics calculations is rarely found to be adequate. For electron-transfer
      reactions not in the inverted region, the common physical picture that diabatic
      processes occur because of surface hopping at the transition state is proven
      inadequate as the DC acts first to block access, increasing the transition state
      energy by (homega)(2)lambda/16J(2) (where lambda is the reorganization energy, J
      the electronic coupling and omega the vibration frequency). However, the rate
      constant in the weakly-coupled Golden-Rule limit is identified as being only
      inversely proportional to this change rather than exponentially damped, owing to
      the effects of tunneling and surface hopping. Such weakly-coupled long-range
      electron-transfer processes should therefore not be described as "non-adiabatic"
      processes as they are easily described by Born-Huang ground-state adiabatic
      surfaces made by adding the DC to the BO surfaces; instead, they should be called
      just "non-Born-Oppenheimer" processes. The model system studied consists of two
      diabatic harmonic potential-energy surfaces coupled linearly through a single
      vibration, the "two-site Holstein model". Analytical expressions are derived for
      the BO breakdown terms, and the model is solved over a large parameter space
      focusing on both the lowest-energy spectroscopic transitions and the quantum
      dynamics of coherent-state wavepackets. BO breakdown is investigated pertinent
      to: ammonia inversion, aromaticity in benzene, the Creutz-Taube ion, the
      bacterial photosynthetic reaction centre, BNB, the molecular conductor Alq3, and
      inverted-region charge recombination in a ferrocene-porphyrin-fullerene triad
      photosynthetic model compound. Throughout, the fundamental nature of BO breakdown
      is linked to the properties of the cusp catastrophe: the cusp diameter is shown
      to determine the magnitudes of all couplings, numerical basis-set and trajectory
      integration requirements, and to determine the transmission coefficient kappa
      used to understand deviations from transition-state theory. 

PMID- 26196266
TI  - Extensive Nosocomial Transmission of Measles Originating in Cruise Ship
      Passenger, Sardinia, Italy, 2014.
AB  - We report a measles outbreak in Sardinia, Italy, that originated in a cruise ship
      passenger. The outbreak showed extensive nosocomial transmission (44 of 80
      cases). To minimize nosocomial transmission, health care facilities should ensure
      that susceptible health care workers are vaccinated against measles and should
      implement effective infection control procedures. 

PMID- 26196267
TI  - Functionalized Polysilsesquioxane-Based Hybrid Silica Solid Amine Sorbents for
      the Regenerative Removal of CO2 from Air.
AB  - Functionalized polysilsesquioxane-based hybrid silica materials are presented as
      solid amine sorbents for direct CO2 capture from air. The sorbent was synthesized
      from amine and vinyl functionalized alkoxysilanes by a simple, energy efficient,
      and cost-effective co-condensation method. The material, containing bound amine
      functionalities, was found to have a selective CO2 capturing capacity of 1.68
      mmol/g from atmospheric air with an adsorption half time of 50 min. This material
      also showed a maximum adsorption capacity of 2.28 mmol/g in pure CO2 and 1.92
      mmol/g in 10% CO2. Desorption started at a temperature as low as 60  degrees C,
      and complete desorption occurred at 80  degrees C. The sorbent exhibited high
      recycling ability, and 100 cycles of adsorption/desorption were demonstrated in
      pure CO2 and 50 cycles in ambient air without any loss in efficiency. 

PMID- 26196268
TI  - Advancing Model Systems for Fundamental Laboratory Studies of Sea Spray Aerosol
      Using the Microbial Loop.
AB  - Sea spray aerosol (SSA) particles represent one of the most abundant surfaces
      available for heterogeneous reactions to occur upon and thus profoundly alter the
      composition of the troposphere. In an effort to better understand tropospheric
      heterogeneous reaction processes, fundamental laboratory studies must be able to
      accurately reproduce the chemical complexity of SSA. Here we describe a new
      approach that uses microbial processes to control the composition of seawater and
      SSA particle composition. By inducing a phytoplankton bloom, we are able to
      create dynamic ecosystem interactions between marine microorganisms, which serve
      to alter the organic mixtures present in seawater. Using this controlled
      approach, changes in seawater composition become reflected in the chemical
      composition of SSA particles 4 to 10 d after the peak in chlorophyll-a. This
      approach for producing and varying the chemical complexity of a dominant
      tropospheric aerosol provides the foundation for further investigations of the
      physical and chemical properties of realistic SSA particles under controlled
      conditions. 

PMID- 26196269
TI  - Pattern of Female Sexual Assault in Qalyubia Governorate, Egypt, During the
      Period From 2009 to 2013: A Retrospective Study.
AB  - Sexual assault is a serious social problem that affects women's life. In Egypt,
      there is no accurate epidemiological study on sexual assault, although it has
      undergone a dramatic surge in 2013. The goals of this study were to estimate the
      prevalence and the characteristics of sexual assault against female in Qalyubia
      Governorate, Egypt. It is a retrospective study evaluating sexual assault against
      females from 2009 to 2013. Total numbers of cases of female sexual assault was
      130 over the studied years. The mean (SD) age of victims was 15.2 (6) years
      ranging from 4 to 40 years. Fifty-eight percent fall in the age group of 12 to 18
      years. Most victims (61.5%) came from urban areas. Summer was relatively a
      vulnerable season for sexual assault (53.1%); 81.5% of victims was unmarried and
      94.6% with normal mentality. The highest percentage of sexual assault crime was
      found in females with primary education (44.6%). Twenty-two (16.9%) of the
      assaulted cases were considered intrafamilial assault, whereas 83.1% were
      extrafamilial. The most common location for assaults was at the assailant's home
      (50.8%), and 80% of the victims were exposed to assault by 1 assailant. The
      shortest time between alleged assault and the examination was 1 day in 12 cases
      (9.2%). The most frequent type of assault was complete vaginal penetration
      (48.55%). The most common type of physical injury was abrasions (48.1%), whereas
      the least was burn or broken teeth (1.3% for each). The highest percentage of
      genital injury was lacerations (36.4%), and the most common location was the
      hymen (36.4%). 

PMID- 26196270
TI  - Head Trauma and Alcohol: A Lethal Combination.
AB  - There has been much recent attention regarding "concussions" and the role they
      may play in death. As most medical professionals are aware, concussions exist on
      a spectrum ranging from minimal or no loss of consciousness with no residual
      sequelae to diffuse axonal injury and sudden death. The location on the spectrum
      depends not only on the nature of the impact or blow but also on the state of the
      individual impacted. Three previous reports have illustrated 7 deaths due to
      blunt force head trauma with acute ethanol intoxication (postconcussive apnea).
      The present report describes 6 additional deaths, five of which were witnessed.
      The report discusses the pathophysiology of postconcussive apnea and concludes
      that the head trauma results in a concussion, which when combined with the
      ethanol, results in prolonged apnea by disruption of the cardiorespiratory
      centers leading to death. In addition, it is concluded that individuals dying
      from postconcussive apnea become immediately unresponsive after the head trauma,
      demonstrate no significant anatomic abnormalities at autopsy, and have blood
      ethanol concentrations ranging from 0.168 to 0.33 g/dL (mean, 0.258 g/dL; median,
      0.24 g/dL). 

PMID- 26196271
TI  - Deaths in Custody: A 25-Year Review of Jail Deaths in Bexar County, Texas.
AB  - Although deaths in custody are an expected occurrence, they are often subjected
      to increased scrutiny and raise many questions as to circumstances surrounding
      the death as well as the cause and manner of death. It is usually the
      responsibility of the medical examiner to answer these questions. Relatively few
      studies have reviewed the causes and manners of death that occur while in custody
      and even fewer specific to jail populations. This study reviews the cause and
      manner of death of persons in custody in an urban county from 1985 to 2010. A
      retrospective review of death investigations, including death certificates and
      autopsy reports, was conducted on all deaths that occurred in custody during the
      period. The age and sex of the decedent as well as the place of death were also
      recorded. Most deaths were attributed to natural disease followed by suicide, and
      most deaths occurred either in the emergency department or in the hospital.
      Regarding the cause of death, cardiovascular disease followed by suicide by
      hanging accounted for the most number of deaths (25% and 20% of all deaths,
      respectively). It is recommended that all deaths in custody be reported to the
      medical examiner and that a thorough death investigation be conducted to properly
      define and document the cause and manner of death. This is particularly important
      given the increased scrutiny to which deaths in custody are often subjected. 

PMID- 26196274
TI  - Cited but not read and read but not cited.

PMID- 26196273
TI  - Development of antimigraine transdermal delivery systems of pizotifen malate.
AB  - The aim of this study was to develop and evaluate a transdermal delivery system
      of pizotifen malate. Pizotifen is frequently used in the preventive treatment of
      migraine, but is also indicated in eating disorders. In the course of the
      project, the effects of chemical enhancers such as ethanol, 1,8-cineole,
      limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic,
      linoleic and oleic acids) were determined, first using a pizotifen solution.
      Steady state flux, diffusion and partition parameters were estimated by fitting
      the Scheuplein equation to the data obtained. Among the chemical enhancers
      studied, decenoic acid showed the highest enhancement activity, which seemed to
      be due to the length of its alkyl chain and unsaturation at the 9th carbon. The
      influence of iontophoresis and the involvement of electrotransport in said
      process was determined. The absorption profile obtained with iontophoresis was
      similar to that obtained with fatty acids and terpenes, though skin deposition of
      the drug was lower with the former. Transdermal delivery systems (TDS) of
      pizotifen were manufactured by including chemical enhancers, decenoic acid or
      oleic acid, and were subsequently characterized. When the results obtained with
      solutions were compared with those obtained with the TDS, a positive enhancement
      effect was observed with the latter with respect to the partitioning and
      diffusion of the drug across the skin. Our findings endorse the suitability of
      our TDS for delivering therapeutic amounts of pizotifen malate. 

PMID- 26196275
TI  - Investigation on the aerosol performance of dry powder inhalation hypromellose
      capsules with different lubricant levels.
AB  - HPMC capsules are made by a dipping process and a surface lubricant for the mould
      pins is an essential processing aid for removing dried capsules shells. For the
      purpose of this study, the level was determined by quantifying methyloleate (MO)
      a component found in the lubricant but not in the hypromellose capsules. Here we
      investigated the influence of the lubricant, low (10.81 MUg/capsule=60 mg/kg MO),
      medium (15.97 MUg/capsule=90 mg/kg MO) and high (23.23 MUg/capsule=127 mg/kg MO)
      content on powder (binary mixture of salbutamol: lactose, 1:50 w/w)
      aerosolization properties was investigated. Results indicated significantly lower
      emitted dose from capsules with 60 mg/kg MO. Furthermore, the 90 and 127 mg/kg MO
      level of lubricant capsules produced almost double the Fine Particle Dose & Fine
      Particle Fraction compared with the low level of lubricant. The data indicates
      that lubricant level within capsules has an influence on deposition profiles and
      amount of drug remaining in capsule and inhaler device after actuation. It is
      suggested lubricant levels greater than 60 mg/kg MO per capsule are required to
      minimise powder retention within capsules and maximise deposition profiles. AFM
      (atomic force microscopy) data suggest that internal surface roughness may be
      related with this phenomena.

PMID- 26196272
TI  - Metabolomics: Applications and Promise in Mycobacterial Disease.
AB  - Until recently, the study of mycobacterial diseases was trapped in culture-based
      technology that is more than a century old. The use of nucleic acid amplification
      is changing this, and powerful new technologies are on the horizon. Metabolomics,
      which is the study of sets of metabolites of both the bacteria and host, is being
      used to clarify mechanisms of disease, and can identify changes leading to better
      diagnosis, treatment, and prognostication of mycobacterial diseases. Metabolomic
      profiles are arrays of biochemical products of genes in their environment. These
      complex patterns are biomarkers that can allow a more complete understanding of
      cell function, dysfunction, and perturbation than genomics or proteomics.
      Metabolomics could herald sweeping advances in personalized medicine and clinical
      trial design, but the challenges in metabolomics are also great. Measured
      metabolite concentrations vary with the timing within a condition, the intrinsic
      biology, the instruments, and the sample preparation. Metabolism profoundly
      changes with age, sex, variations in gut microbial flora, and lifestyle.
      Validation of biomarkers is complicated by measurement accuracy, selectivity,
      linearity, reproducibility, robustness, and limits of detection. The statistical
      challenges include analysis, interpretation, and description of the vast amount
      of data generated. Despite these drawbacks, metabolomics provides great
      opportunity and the potential to understand and manage mycobacterial diseases. 

PMID- 26196276
TI  - Preparation, characterization and buccal permeation of naratriptan.
AB  - Naratriptan (NAR) is currently used for the management of migraine as the
      hydrochloride salt (NAR.HCl) and is administered as an oral tablet. This work
      evaluates the feasibility of buccal delivery of NAR in order to ensure faster
      onset of action and avoid the side-effects associated with conventional oral
      formulations. We hypothesized that the unionized form of NAR would permeate
      buccal tissue to a greater extent than the salt. Therefore the first stage of
      this work required preparation of the free base from NAR.HCl. Characterisation of
      the base with thermal and elemental analyses confirmed its purity; logP and logD
      values were also determined. The pH permeation profile of NAR was also determined
      in the range 7.4-10. Solubility studies in non-aqueous solvents indicated that
      TranscutolTM (TC) and dipropylene glycol (DPG) were suitable vehicles for the
      free base. Maximum amounts of NAR which permeated after 6h were ~ 130 MUg/cm(2).
      Based on the pH permeation results and studies conducted at two different doses
      NAR appears to permeate porcine buccal tissue via the transcellular route.
      Finally, estimates of likely systemic values suggest that optimised formulations
      should be taken forward for in vivo evaluation.

PMID- 26196277
TI  - Characteristic of core materials in polymeric micelles effect on their micellar
      properties studied by experimental and dpd simulation methods.
AB  - Polymeric micelles are one important class of nanoparticles for anticancer drug
      delivery, but the impact of hydrophobic segments on drug encapsulation and
      release is unclear, which deters the rationalization of drug encapsulation into
      polymeric micelles. This paper focused on studying the correlation between the
      characteristics of hydrophobic segments and encapsulation of structurally
      different drugs (DOX and beta-carotene). Poly(epsilon-caprolactone) (PCL) or
      poly(l-lactide) (PLLA) were used as hydrophobic segments to synthesize micelle
      forming amphiphilic block copolymers with the hydrophilic methoxy-poly(ethylene
      glycol) (mPEG). Both blank and drug loaded micelles were spherical in shape with
      sizes lower than 50 nm. PCL-based micelles exhibited higher drug loading capacity
      than their PLLA-based counterparts. Higher encapsulation efficiency of beta
      carotene was achieved compared with DOX. In addition, both doxorubicin and beta
      carotene were released much faster from PCL-based polymeric micelles. Dissipative
      particle dynamics (DPD) simulation revealed that the two drugs tended to
      aggregate in the core of the PCL-based micelles but disperse in the core of PLLA
      based micelles. In vitro cytotoxicity investigation of DOX loaded micelles
      demonstrated that a faster drug release warranted a more efficient cancer-killing
      effect. This research could serve as a guideline for the rational design of
      polymeric micelles for drug delivery.

PMID- 26196278
TI  - Statin use and the risk of cirrhosis development in patients with hepatitis C
      virus infection.
AB  - BACKGROUND & AIMS: Several animal studies have shown that statins can inhibit the
      progression of cirrhosis; however, few clinical studies have been conducted.
      Previous studies have indicated that statins can prevent the progression of
      hepatic fibrosis in patients with hepatitis C virus (HCV) infection and advanced
      hepatic fibrosis, however data is lacking on patients who have yet to progress to
      cirrhosis. This study investigated the association between the use of statin and
      the risk of cirrhosis development in patients with HCV infection. METHODS: We
      conducted a population-based cohort study by using the Taiwan National Health
      Insurance Research Database. A total of 226,856 patients with HCV infection were
      included as the study cohort. Each patient was followed from 1997 to 2010 to
      identify incident cases of cirrhosis. A Cox proportional hazard regression was
      performed to evaluate the association between statin use and cirrhosis risk.
      RESULTS: A total of 34,273 cases of cirrhosis were identified in the cohort with
      HCV infection during the follow-up period of 2,874,031.7 person-years. The
      incidence rate was 445.5 cases of cirrhosis per 100,000 person-years (95%
      confidence interval (CI), 423.3 to 465.7) for statin users (defined as those who
      used more than 28 cumulative defined daily doses (cDDD)), and 1311.2 cirrhosis
      cases per 100,000 person-years (95% CI, 1297.1 to 1325.6) for non-users. A dose
      response relationship between statin use and cirrhosis risk was observed. The
      adjusted hazard ratios were 0.33 (95% CI, 0.31 to 0.36), 0.24 (95% CI, 0.22 to
      0.25), and 0.13 (95% CI, 0.12 to 0.15) for statin use of 28 to 83, 84 to 365, and
      more than 365 cDDD, respectively, relative to no statin use (<28 cDDD).
      CONCLUSION: Among the patients with HCV infection, statin use was associated with
      a reduced risk of cirrhosis development in a dose-dependent manner. Further
      clinical research is required.

PMID- 26196279
TI  - Random Terpolymer Designed with Tunable Fluorescence Lifetime for Efficient
      Organic/Inorganic Hybrid Solar Cells.
AB  - The long photoluminescence lifetime of the organic semiconductor materials is of
      great importance in assuring the photoexcited extion to have enough time to
      achieve successful separation at the interface and improving the performances of
      organic/inorganic hybrid solar cells. Unfortunately, many efforts have been
      devoted to the bandgap or molecular energy level control, whereas this viewpoint
      is rarely referred. Herein, we prepare a random D-A terpolymers based on PZT and
      BDT cores in conjugation with electron withdrawing BT unit and explore their
      applications in HSCs. Except for the energy level and the bandgap, the role that
      monomers ratio plays in photoluminescence lifetime is particularly involved. As a
      result, the average PL lifetimes of the terpolymer are significantly tuned. The
      optimized terpolymer exhibits a longer PL lifetime and prominent charge transfer
      ability, thus leading to a notable enhancement of PCE when compared with its
      counterparts, although their bandgaps and molecular energy levels are almost the
      same. 

PMID- 26196280
TI  - Gender Inequality in the Couple Relationship and Leisure-Based Physical Exercise.
AB  - AIMS: To analyse whether gender inequality in the couple relationship was related
      to leisure-based physical activity, after controlling for earlier physical
      activity and confounders. METHODS: Data drawn from the Northern Swedish Cohort of
      all pupils in their final year of compulsory schooling in a town in the North of
      Sweden. The sample consisted of 772 respondents (n = 381 men, n = 391 women) in
      the 26-year follow-up (in 2007, aged 42) who were either married or cohabiting.
      Ordinal regression, for men and women separately, was used to assess the
      association between gender inequality (measured as self-perceived equality in the
      couple relationship using dummy variables) and a measure of exercise frequency,
      controlling for prior exercise frequency, socioeconomic status, the presence of
      children in the home, and longer than usual hours in paid work. RESULTS: The
      perception of greater gender equality in the couple relationship was associated
      with higher levels of physical activity for both men and women. This remained
      significant when the other variables were controlled for. Amongst men the
      confidence intervals were high. CONCLUSIONS: The results point to the potential
      of perceived gender equality in the couple relationship to counteract the general
      time poverty and household burden that often arises from the combination of paid
      work and responsibility for children and the home, especially for women. The high
      confidence intervals among men indicate the need for more research within the
      field with larger samples.

PMID- 26196281
TI  - Characterization of Chromosome Inheritance of the Intergeneric BC2 and BC3
      Progeny between Saccharum spp. and Erianthus arundinaceus.
AB  - Erianthus arundinaceus (E. arundinaceus) has many desirable agronomic traits for
      sugarcane improvement, such as high biomass, vigor, rationing ability, tolerance
      to drought, and water logging, as well as resistance to pests and disease. To
      investigate the introgression of the E. arundinaceus genome into sugarcane in the
      higher generations, intergeneric BC2 and BC3 progeny generated between Saccharum
      spp. and E. arundinaceus were studied using the genomic in situ hybridization
      (GISH) technique. The results showed that the BC2 and BC3 generations resulted
      from n + n chromosome transmission. Furthermore, chromosome translocation
      occurred at terminal fragments from the E. arundinaceus chromosome in some
      progeny of Saccharum spp. and E. arundinaceus. Notably, the translocated
      chromosomes could be stably transmitted to their progeny. This study illustrates
      the characterization of chromosome inheritance of the intergeneric BC2 and BC3
      progeny between Saccharum spp. and E. arundinaceus. This work could provide more
      useful molecular cytogenetic information for the germplasm resources of E.
      arundinaceus, and may promote further understanding of the germplasm resources of
      E. arundinaceus for sugarcane breeders to accelerate its progress in sugarcane
      commercial breeding. 

PMID- 26196282
TI  - Impact of Bioreactor Environment and Recovery Method on the Profile of Bacterial
      Populations from Water Distribution Systems.
AB  - Multiple rotating annular reactors were seeded with biofilms flushed from water
      distribution systems to assess (1) whether biofilms grown in bioreactors are
      representative of biofilms flushed from the water distribution system in terms of
      bacterial composition and diversity, and (2) whether the biofilm sampling method
      affects the population profile of the attached bacterial community. Biofilms were
      grown in bioreactors until thickness stabilized (9 to 11 weeks) and harvested
      from reactor coupons by sonication, stomaching, bead-beating, and manual
      scraping. High-throughput sequencing of 16S rRNA amplicons was used to profile
      bacterial populations from flushed biofilms seeded into bioreactors as well as
      biofilms recovered from bioreactor coupons by different methods. beta diversity
      between flushed and reactor biofilms was compared to beta diversity between (i)
      biofilms harvested from different reactors and (ii) biofilms harvested by
      different methods from the same reactor. These analyses showed that average
      diversity between flushed and bioreactor biofilms was double the diversity
      between biofilms from different reactors operated in parallel. The diversity
      between bioreactors was larger than the diversity associated with different
      biofilm recovery methods. Compared to other experimental variables, the method
      used to recover biofilms had a negligible impact on the outcome of water biofilm
      analyses based on 16S amplicon sequencing. Results from this study show that
      biofilms grown in reactors over 9 to 11 weeks are not representative models of
      the microbial populations flushed from a distribution system. Furthermore, the
      bacterial population profile of biofilms grown in replicate reactors from the
      same flushed water are likely to diverge. However, four common sampling
      protocols, which differ with respect to disruption of bacterial cells, provide
      similar information with respect to the 16S rRNA population profile of the
      biofilm community.

PMID- 26196283
TI  - Designing a Monitoring Program to Estimate Estuarine Survival of Anadromous
      Salmon Smolts: Simulating the Effect of Sample Design on Inference.
AB  - A number of researchers have attempted to estimate salmonid smolt survival during
      outmigration through an estuary. However, it is currently unclear how the design
      of such studies influences the accuracy and precision of survival estimates. In
      this simulation study we consider four patterns of smolt survival probability in
      the estuary, and test the performance of several different sampling strategies
      for estimating estuarine survival assuming perfect detection. The four survival
      probability patterns each incorporate a systematic component (constant, linearly
      increasing, increasing and then decreasing, and two pulses) and a random
      component to reflect daily fluctuations in survival probability. Generally,
      spreading sampling effort (tagging) across the season resulted in more accurate
      estimates of survival. All sampling designs in this simulation tended to under
      estimate the variation in the survival estimates because seasonal and daily
      variation in survival probability are not incorporated in the estimation
      procedure. This under-estimation results in poorer performance of estimates from
      larger samples. Thus, tagging more fish may not result in better estimates of
      survival if important components of variation are not accounted for. The results
      of our simulation incorporate survival probabilities and run distribution data
      from previous studies to help illustrate the tradeoffs among sampling strategies
      in terms of the number of tags needed and distribution of tagging effort. This
      information will assist researchers in developing improved monitoring programs
      and encourage discussion regarding issues that should be addressed prior to
      implementation of any telemetry-based monitoring plan. We believe implementation
      of an effective estuary survival monitoring program will strengthen the
      robustness of life cycle models used in recovery plans by providing missing data
      on where and how much mortality occurs in the riverine and estuarine portions of
      smolt migration. These data could result in better informed management decisions
      and assist in guidance for more effective estuarine restoration projects.

PMID- 26196284
TI  - Clinical Implications of iNOS Levels in Triple-Negative Breast Cancer Responding
      to Neoadjuvant Chemotherapy.
AB  - Triple-negative breast cancer is a high-risk breast cancer with poor survival
      rate. To date, there is a lack of targeted therapy for this type of cancer. One
      unique phenomenon is that inflammatory breast cancer is frequently triple
      negative. However, it is still ambiguous how inflammation influences triple
      negative breast cancer growth and responding to chemotherapy. Herein, we
      investigated the levels of inflammation-associated enzyme, iNOS, in 20 triple
      negative breast cancer patients' tumors, and examined its correlation with
      patients' responses to platinum-based neoadjuvant chemotherapy. Our studies
      showed that triple-negative breast cancer patients with attenuated iNOS levels in
      tumor cells after treatment showed better responses to platinum-based neoadjuvant
      chemotherapy than other triple-negative breast cancer patients. Our further in
      vitro studies confirmed that induction of proper levels of NO increased the
      resistance to cisplatin in triple-negative MDA-MB-231 cells. Our data suggest
      that aberrant high level of iNOS/NO are associated with less effectiveness of
      platinum-based neoadjuvant chemotherapy in triple-negative breast cancer.
      Therefore, we propose to monitor iNOS levels as a new predictor for triple
      negative breast cancer patient's response to platinum-based neoadjuvant
      chemotherapy. Moreover, iNOS/NO is considered as a potential target for
      combination therapy with platinum drugs for triple-negative breast cancer. 

PMID- 26196285
TI  - Peptide Inhibitor of Complement C1 (PIC1) Rapidly Inhibits Complement Activation
      after Intravascular Injection in Rats.
AB  - The complement system has been increasingly recognized to play a pivotal role in
      a variety of inflammatory and autoimmune diseases. Consequently, therapeutic
      modulators of the classical, lectin and alternative pathways of the complement
      system are currently in pre-clinical and clinical development. Our laboratory has
      identified a peptide that specifically inhibits the classical and lectin pathways
      of complement and is referred to as Peptide Inhibitor of Complement C1 (PIC1). In
      this study, we determined that the lead PIC1 variant demonstrates a salt
      dependent binding to C1q, the initiator molecule of the classical pathway.
      Additionally, this peptide bound to the lectin pathway initiator molecule MBL as
      well as the ficolins H, M and L, suggesting a common mechanism of PIC1 inhibitory
      activity occurs via binding to the collagen-like tails of these collectin
      molecules. We further analyzed the effect of arginine and glutamic acid residue
      substitution on the complement inhibitory activity of our lead derivative in a
      hemolytic assay and found that the original sequence demonstrated superior
      inhibitory activity. To improve upon the solubility of the lead derivative, a
      pegylated, water soluble variant was developed, structurally characterized and
      demonstrated to inhibit complement activation in mouse plasma, as well as rat,
      non-human primate and human serum in vitro. After intravenous injection in rats,
      the pegylated derivative inhibited complement activation in the blood by 90%
      after 30 seconds, demonstrating extremely rapid function. Additionally, no
      adverse toxicological effects were observed in limited testing. Together these
      results show that PIC1 rapidly inhibits classical complement activation in vitro
      and in vivo and is functional for a variety of animal species, suggesting its
      utility in animal models of classical complement-mediated diseases.

PMID- 26196286
TI  - Disturbances in Hypothalamic-Pituitary-Adrenal Axis and Immunological Activity
      Differentiating between Unipolar and Bipolar Depressive Episodes.
AB  - INTRODUCTION: Differentiating bipolar depression (BD) from unipolar depression
      (UD) is difficult in clinical practice and, consequently, accurate recognition of
      BD can take as long as nine years. Research has therefore focused on the
      discriminatory capacities of biomarkers, such as markers of the hypothalamic
      pituitary-adrenal (HPA) axis or immunological activity. However, no previous
      study included assessments of both systems, which is problematic as they may
      influence each other. Therefore, this study aimed to explore whether cortisol
      indicators and inflammatory markers were a) independently associated with and/or
      b) showed effect modification in relation to a lifetime (hypo)manic episode in a
      large sample of depressed patients. METHODS: Data were derived from the
      Netherlands Study of Depression and Anxiety and comprised 764 patients with a DSM
      IV depressive disorder at baseline, of which 124 (16.2%) had a lifetime
      (hypo)manic episode at the 2-year assessment, or a more recent episode at the 4
      year or 6-year assessment. Baseline cortisol awakening response, evening cortisol
      and diurnal cortisol slope were considered as cortisol indicators, while baseline
      C-reactive Protein (CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor Alpha
      (TNF-alpha) were included as inflammatory markers. RESULTS: In depressed men and
      women, none of the cortisol indicators and inflammatory markers were
      (independently) associated with a (hypo)manic episode. However, effect
      modification was found of diurnal cortisol slope and CRP in relation to a
      (hypo)manic episode. Further analyses showed that depressed men with high levels
      of diurnal cortisol slope and CRP had an increased odds (OR=10.99, p=.001) of
      having a (hypo)manic episode. No significant differences were found in women.
      CONCLUSION: Our findings suggest that the combination of high diurnal cortisol
      slope and high CRP may differentiate between UD and BD. This stresses the
      importance of considering HPA-axis and immunological activity simultaneously, but
      more research is needed to unravel their interrelatedness.

PMID- 26196287
TI  - Individual Participant Data (IPD) Meta-analyses of Randomised Controlled Trials:
      Guidance on Their Use.
AB  - Jayne Tierney and colleagues offer guidance on how to spot a well-designed and
      well-conducted individual participant data meta-analysis. 

PMID- 26196288
TI  - Bilirubin Oxidase from Myrothecium verrucaria Physically Absorbed on Graphite
      Electrodes. Insights into the Alternative Resting Form and the Sources of
      Activity Loss.
AB  - The oxygen reduction reaction is one of the most important chemical processes in
      energy converting systems and living organisms. Mediator-less, direct electro
      catalytic reduction of oxygen to water was achieved on spectrographite electrodes
      modified by physical adsorption of bilirubin oxidases from Myrothecium
      verrucaria. The existence of an alternative resting form of the enzyme is
      validated. The effect on the catalytic cycle of temperature, pH and the presence
      of halogens in the buffer was investigated. Previous results on the
      electrochemistry of bilirubin oxidase and on the impact of the presence of
      halogens are reviewed and reinterpreted.

PMID- 26196289
TI  - Seasonal, Oceanographic and Atmospheric Drivers of Diving Behaviour in a
      Temperate Seal Species Living in the High Arctic.
AB  - The harbour seal (Phoca vitulina) population in Svalbard marks the northernmost
      limit of the species' range. This small population experiences environmental
      extremes in sea and air temperatures, sea ice cover and also in light regime for
      this normally temperate species. This study deployed Conductivity Temperature
      Depth Satellite Relay Data Loggers (CTD-SRDLs) on 30 adult and juvenile harbour
      seals in 2009 and 2010 to study their foraging behaviour across multiple seasons.
      A total of 189,104 dives and 16,640 CTD casts (mean depth 72 m +/- 59) were
      recorded. Individuals dove to a mean depth of 41 m +/- 24 with a maximum dive
      depth range of 24 - 403 m. Dives lasted on average 204 sec +/- 120 with maximum
      durations ranging between 240 - 2,220 sec. Average daily depth and duration of
      dives, number of dives, time spent diving and dive time/surface time were
      influenced by date, while sex, age, sea-ice concentration and their interactions
      were not particularly influential. Dives were deeper (~150 m), longer (~480 sec),
      less numerous (~250 dives/day) and more pelagic during the winter/early spring
      compared to the fall and animals spent proportionally less time at the bottom of
      their dives during the winter. Influxes of warm saline water, corresponding to
      Atlantic Water characteristics, were observed intermittently at depths ~100 m
      during both winters in this study. The seasonal changes in diving behaviour were
      linked to average weekly wind stresses from the north or north-east, which
      induced upwelling events onto the shelf through offshore Ekman transport. During
      these events the shelf became flooded with AW from the West Spitsbergen Current,
      which presumably brought Atlantic fish species close to shore and within the
      seals' foraging depth-range. Predicted increased in the influx of AW in this
      region are likely going to favour the growth and geographic expansion of this
      harbour seal population in the future.

PMID- 26196290
TI  - Estimating the Cost-Effectiveness of HIV Prevention Programmes in Vietnam, 2006
      2010: A Modelling Study.
AB  - INTRODUCTION: Vietnam has been largely reliant on international support in its
      HIV response. Over 2006-2010, a total of US$480 million was invested in its HIV
      programmes, more than 70% of which came from international sources. This study
      investigates the potential epidemiological impacts of these programmes and their
      cost-effectiveness. METHODS: We conducted a data synthesis of HIV programming,
      spending, epidemiological, and clinical outcomes. Counterfactual scenarios were
      defined based on assumed programme coverage and behaviours had the programmes not
      been implemented. An epidemiological model, calibrated to reflect the actual
      epidemiological trends, was used to estimate plausible ranges of programme
      impacts. The model was then used to estimate the costs per averted infection,
      death, and disability adjusted life-year (DALY). RESULTS: Based on observed
      prevalence reductions amongst most population groups, and plausible
      counterfactuals, modelling suggested that antiretroviral therapy (ART) and
      prevention programmes over 2006-2010 have averted an estimated 50,600 [95%
      uncertainty bound: 36,300-68,900] new infections and 42,600 [36,100-54,100]
      deaths, resulting in 401,600 [312,200-496,300] fewer DALYs across all population
      groups. HIV programmes in Vietnam have cost an estimated US$1,972 [1,447-2,747],
      US$2,344 [1,843-2,765], and US$248 [201-319] for each averted infection, death,
      and DALY, respectively. CONCLUSIONS: Our evaluation suggests that HIV programmes
      in Vietnam have most likely had benefits that are cost-effective. ART and direct
      HIV prevention were the most cost-effective interventions in reducing HIV disease
      burden.

PMID- 26196291
TI  - Numerical Investigation of the Effect of Unsteadiness on Three-Dimensional Flow
      of an Oldroyb-B Fluid.
AB  - A spectral relaxation method used with bivariate Lagrange interpolation is used
      to find numerical solutions for the unsteady three-dimensional flow problem of an
      Oldroyd-B fluid with variable thermal conductivity and heat generation. The
      problem is governed by a set of three highly coupled nonlinear partial
      differential equations. The method, originally used for solutions of systems of
      ordinary differential equations is extended to solutions of systems of nonlinear
      partial differential equations. The modified approach involves seeking solutions
      that are expressed as bivariate Lagrange interpolating polynomials and applying
      pseudo-spectral collocation in both independent variables of the governing PDEs.
      Numerical simulations were carried out to generate results for some of the
      important flow properties such as the local skin friction and the heat transfer
      rate. Numerical analysis of the error and convergence properties of the method
      are also discussed. One of the benefits of the proposed method is that it is
      computationally fast and gives very accurate results after only a few iterations
      using very few grid points in the numerical discretization process. 

PMID- 26196292
TI  - Correction: Subretinal Fluid in Eyes with Active Ocular Toxoplasmosis Observed
      Using Spectral Domain Optical Coherence Tomography.

PMID- 26196293
TI  - Health Care-Associated Infection Outbreak Investigations in Outpatient Settings,
      Los Angeles County, California, USA, 2000-2012.
AB  - Health care services are increasingly delivered in outpatient settings. However,
      infection control oversight in outpatient settings to ensure patient safety has
      not improved and literature quantifying reported health care-associated infection
      outbreaks in outpatient settings is scarce. The objective of this analysis was to
      characterize investigations of suspected and confirmed outbreaks in outpatient
      settings in Los Angeles County, California, USA, reported during 2000-2012, by
      using internal logs; publications; records; and correspondence of outbreak
      investigations by characteristics of the setting, number, and type of infection
      control breaches found during investigations, outcomes of cases, and public
      health responses. Twenty-eight investigations met the inclusion criteria.
      Investigations occurred frequently, in diverse settings, and required substantial
      public health resources. Most outpatient settings investigated had >1 infection
      control breach. Lapses in infection control were suspected to be the outbreak
      source for 16 of the reviewed investigations. 

PMID- 26196294
TI  - A Big Five approach to self-regulation: personality traits and health
      trajectories in the Hawaii longitudinal study of personality and health.
AB  - Self-regulatory processes influencing health outcomes may have their origins in
      childhood personality traits. The Big Five approach to personality was used here
      to investigate the associations between childhood traits, trait-related
      regulatory processes and changes in health across middle age. Participants (N =
      1176) were members of the Hawaii longitudinal study of personality and health.
      Teacher assessments of the participants' traits when they were in elementary
      school were related to trajectories of self-rated health measured on 6 occasions
      over 14 years in middle age. Five trajectories of self-rated health were
      identified by latent class growth analysis: Stable Excellent, Stable Very Good,
      Good, Decreasing and Poor. Childhood Conscientiousness was the only childhood
      trait to predict membership in the Decreasing class vs. the combined healthy
      classes (Stable Excellent, Stable Very Good and Good), even after controlling for
      adult Conscientiousness and the other adult Big Five traits. The Decreasing class
      had poorer objectively assessed clinical health measured on one occasion in
      middle age, was less well-educated, and had a history of more lifespan health
      damaging behaviors compared to the combined healthy classes. These findings
      suggest that higher levels of childhood Conscientiousness (i.e. greater self
      discipline and goal-directedness) may prevent subsequent health decline decades
      later through self-regulatory processes involving the acquisition of lifelong
      healthful behavior patterns and higher educational attainment.

PMID- 26196295
TI  - Multidimensional Measurement of Household Water Poverty in a Mumbai Slum: Looking
      Beyond Water Quality.
AB  - OBJECTIVE: A focus on bacterial contamination has limited many studies of water
      service delivery in slums, with diarrheal illness being the presumed outcome of
      interest. We conducted a mixed methods study in a slum of 12,000 people in
      Mumbai, India to measure deficiencies in a broader array of water service
      delivery indicators and their adverse life impacts on the slum's residents.
      METHODS: Six focus group discussions and 40 individual qualitative interviews
      were conducted using purposeful sampling. Quantitative data on water indicators
      quantity, access, price, reliability, and equity-were collected via a structured
      survey of 521 households selected using population-based random sampling.
      RESULTS: In addition to negatively affecting health, the qualitative findings
      reveal that water service delivery failures have a constellation of other adverse
      life impacts-on household economy, employment, education, quality of life, social
      cohesion, and people's sense of political inclusion. In a multivariate logistic
      regression analysis, price of water is the factor most strongly associated with
      use of inadequate water quantity (<=20 liters per capita per day). Water service
      delivery failures and their adverse impacts vary based on whether households
      fetch water or have informal water vendors deliver it to their homes.
      CONCLUSIONS: Deficiencies in water service delivery are associated with many non
      health-related adverse impacts on slum households. Failure to evaluate non-health
      outcomes may underestimate the deprivation resulting from inadequate water
      service delivery. Based on these findings, we outline a multidimensional
      definition of household "water poverty" that encourages policymakers and
      researchers to look beyond evaluation of water quality and health. Use of
      multidimensional water metrics by governments, slum communities, and researchers
      may help to ensure that water supplies are designed to advance a broad array of
      health, economic, and social outcomes for the urban poor.

PMID- 26196296
TI  - The Continuing Growth of Global Cooperation Networks in Research: A Conundrum for
      National Governments.
AB  - Global collaboration continues to grow as a share of all scientific cooperation,
      measured as coauthorships of peer-reviewed, published papers. The percent of all
      scientific papers that are internationally coauthored has more than doubled in 20
      years, and they account for all the growth in output among the scientifically
      advanced countries. Emerging countries, particularly China, have increased their
      participation in global science, in part by doubling their spending on R&D; they
      are increasingly likely to appear as partners on internationally coauthored
      scientific papers. Given the growth of connections at the international level, it
      is helpful to examine the phenomenon as a communications network and to consider
      the network as a new organization on the world stage that adds to and complements
      national systems. When examined as interconnections across the globe over two
      decades, a global network has grown denser but not more clustered, meaning there
      are many more connections but they are not grouping into exclusive 'cliques'.
      This suggests that power relationships are not reproducing those of the political
      system. The network has features an open system, attracting productive scientists
      to participate in international projects. National governments could gain
      efficiencies and influence by developing policies and strategies designed to
      maximize network benefits-a model different from those designed for national
      systems. 

PMID- 26196297
TI  - Transcriptional Analyses of Mandarins Seriously Infected by 'Candidatus
      Liberibacter asiaticus'.
AB  - A range of leaf symptoms, including blotchy mottle, yellowing, and small, upright
      leaves with a variety of chlorotic patterns resembling those induced by zinc
      deficiencies, are associated with huanglongbing (HLB, yellow shoot disease), a
      worldwide destructive citrus disease. HLB is presumably caused by the phloem
      limited fastidious prokaryotic alpha-proteobacterium 'Candidatus Liberibacter
      spp.' Previous studies focused on the proteome and transcriptome analyses of
      citrus 5 to 35 weeks after 'Ca. L. spp.' inoculation. In this study, gene
      expression profiles were analyzed from mandarin Citrus reticulate Blanco cv.
      jiaogan leaves after a 2 year infection with 'Ca. L. asiaticus'. The Affymetrix
      microarray analysis explored 2,017 differentially expressed genes. Of the 1,364
      genes had known functions, 938 (46.5%) were up-regulated. Genes related to
      photosynthesis, carbohydrate metabolic, and structure were mostly down-regulated,
      with rates of 92.7%, 61.0%, and 80.2%, respectively. Genes associated with
      oxidation-reduction and transport were mostly up-regulated with the rates of
      75.0% and 64.6%, respectively. Our data analyses implied that the infection of
      'Ca. L. asiaticus' could alter hormone crosstalk, inducing the jasmine acid
      pathway and depressing the ethylene and salicylic acid pathways in the citrus
      host. This study provides an enhanced insight into the host response of citrus to
      'Ca. L. asiaticus' infection at a two-years infection stage.

PMID- 26196298
TI  - Exposure to Bisphenol A and Phthalates during Pregnancy and Ultrasound Measures
      of Fetal Growth in the INMA-Sabadell Cohort.
AB  - BACKGROUND: Prenatal exposure to bisphenol A (BPA) and phthalates may affect
      fetal growth; however, previous findings are inconsistent and based on few
      studies. OBJECTIVES: We assessed whether prenatal exposure to BPA and phthalates
      was associated with fetal growth in a Spanish birth cohort of 488 mother-child
      pairs. METHODS: We measured BPA and eight phthalates [four di(2-ethylhexyl)
      phthalate metabolites (DEHPm), mono-benzyl phthalate (MBzP), and three low
      molecular-weight phthalate metabolites (LMWPm)] in two spot-urine samples
      collected during the first and third trimester of pregnancy. We estimated growth
      curves for femur length (FL), head circumference (HC), abdominal circumference
      (AC), biparietal diameter (BPD), and estimated fetal weight (EFW) during
      pregnancy (weeks 12-20 and 20-34), and for birth weight, birth length, head
      circumference at birth, and placental weight. RESULTS: Overall, results did not
      support associations of exposure to BPA or DEHPm during pregnancy with fetal
      growth parameters. Prenatal MBzP exposure was positively associated with FL at 20
      34 weeks, resulting in an increase of 3.70% of the average FL (95% CI: 0.75,
      6.63%) per doubling of MBzP concentration. MBzP was positively associated with
      birth weight among boys (48 g; 95% CI: 6, 90) but not in girls (-27 g; 95% CI: 
      79, 25) (interaction p-value = 0.04). The LMWPm mono-n-butyl phthalate (MnBP) was
      negatively associated with HC at 12-20 pregnancy weeks [-4.88% of HC average (95%
      CI: -8.36, -1.36%)]. CONCLUSIONS: This study, one of the first to combine repeat
      exposure biomarker measurements and multiple growth measures during pregnancy,
      finds little evidence of associations of BPA or phthalate exposures with fetal
      growth. Phthalate metabolites MBzP and MnBP were associated with some fetal
      growth parameters, but these findings require replication. CITATION: Casas M,
      Valvi D, Ballesteros-Gomez A, Gascon M, Fernandez MF, Garcia-Esteban R, Iniguez
      C, Martinez D, Murcia M, Monfort N, Luque N, Rubio S, Ventura R, Sunyer J,
      Vrijheid M. 2016. Exposure to bisphenol A and phthalates during pregnancy and
      ultrasound measures of fetal growth in the INMA-Sabadell cohort. Environ Health
      Perspect 124:521-528; http://dx.doi.org/10.1289/ehp.1409190.

PMID- 26196299
TI  - Influence of Sex on Basal and Dickkopf-1 Regulated Gene Expression in the Bovine
      Morula.
AB  - Sex affects function of the developing mammalian embryo as early as the
      preimplantation period. There were two goals of the current objective. The first
      was to determine the degree and nature of differences in gene expression between
      female and male embryos in the cow at the morula stage of development. The second
      objective was to determine whether DKK1, a molecule known to alter
      differentiation of the blastocyst, would affect gene expression differently for
      female and male morulae. In Experiment 1, female and male embryos were treated
      with DKK1 at Day 5 after insemination. Morulae were harvested 24 h after
      treatment, pooled in groups of 20 for microarray analysis and RNA subjected to
      analysis of gene expression by microarray hybridization. There were 662
      differentially expressed genes between females and males and 128 of these genes
      had a fold change >= 1.5 between the two sexes. Of the genes upregulated in
      females, 49.5% were located in the X chromosome. Functional analysis predicted
      that cell survival was greater in female embryos. Experiment 2 involved a similar
      design except that transcripts for 12 genes previously reported to be affected by
      sex, DKK1 or the interaction were quantified by quantitative polymerase chain
      reaction. Expression of all genes tested that were affected by sex in experiment
      1 was affected in a similar manner in Experiment 2. In contrast, effects of DKK1
      on gene expression were largely not repeatable in Experiment 2. The exception was
      for the Hippo signaling gene AMOT, which was inhibited by DKK1. In Experiment 3,
      embryos produced by fertilization with unsorted sperm were treated with DKK1 at
      Day 5 and abundance of transcripts for CDX2, GATA6, and NANOG determined at Days
      5, 6 and 7 after insemination. There was no effect of DKK1 on expression of any
      of the three genes. In conclusion, female and male bovine embryos have a
      different pattern of gene expression as early as the morula stage, and this is
      due to a large extent to expression of genes in the X chromosomes in females.
      Differential gene expression between female and male embryos is likely the basis
      for increased resistance to cell death signals in female embryos and disparity in
      responses of female and male embryos to changes in the maternal environment. 

PMID- 26196300
TI  - The hypotensive effect of acute and chronic AMP-activated protein kinase
      activation in normal and hyperlipidemic mice.
AB  - AMP-activated protein kinase (AMPK) is present in the arterial wall and is
      activated in response to cellular stressors that raise AMP relative to ADP/ATP.
      Activation of AMPK in vivo lowers blood pressure but the influence of
      hyperlipidemia on this response has not been studied. ApoE(-/-) mice on high fat
      diet for 6weeks and age-matched controls were treated with the AMPK activator,
      AICAR daily for two weeks. Under anesthesia, the carotid artery was cannulated
      for blood pressure measurements. Aortic tissue was removed for in vitro
      functional experiments and AMPK activity was measured in artery homogenates by
      Western blotting. ApoE(-/-) mice had significantly raised mean arterial pressure;
      chronic AICAR treatment normalized this but had no effect in normolipidemic mice,
      whereas acute administration of AICAR lowered mean arterial pressure in both
      groups. Chronic AICAR treatment increased phosphorylation of AMPK and its
      downstream target acetyl-CoA carboxylase in normolipidemic but not ApoE(-/-)
      mice. In aortic rings, AMPK activation induced vasodilation and an
      anticontractile effect, which was attenuated in ApoE(-/-) mice. This study
      demonstrates that hyperlipidemia dysregulates the AMPK pathway in the arterial
      wall but this effect can be reversed by AMPK activation, possibly through
      improving vessel compliance. 

PMID- 26196301
TI  - Mechanism of hydralazine-induced relaxation in resistance arteries during
      pregnancy: Hydralazine induces vasodilation via a prostacyclin pathway.
AB  - The cellular mechanisms of hydralazine-induced relaxation were investigated in
      isolated mesenteric resistance arteries from pregnant rats. Administration of
      hydralazine relaxed phenylephrine-constricted mesenteric arteries with an EC50 of
      3.6 +/- 0.3 MUM and an efficacy of 75 +/- 6.2%. These vasodilatory effects were
      abolished by: (1) preconstriction with a potassium depolarizing solution, (2)
      endothelial denudation (for concentrations of hydralazine<10 MUM), (3) addition
      of non-selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors, and (4)
      pretreatment with a prostacyclin receptor antagonist (R01138452). Nitric oxide
      synthase (NOS) inhibition did not significantly alter the sensitivity or
      magnitude of the vasodilatory response; surprisingly, exposure to hydralazine
      also did not elevate endothelial cell Ca(2+), suggesting a novel mechanism of
      activation. In summary, hydralazine is a potent resistance artery vasodilator
      that affects both endothelial and vascular smooth muscle (VSM) cells in a
      concentration-dependent manner. At clinically relevant concentrations (<10 MUM),
      its effects in the splanchnic resistance vasculature are: (1) primarily
      endothelial in origin, require (2) hyperpolarization and (3) activation of COX,
      and (4) are mediated by the PGI2 (IP) receptor.

PMID- 26196302
TI  - Significance of the antiangiogenic mechanisms of thalidomide in the therapy of
      diabetic retinopathy.
AB  - Diabetic retinopathy is an ocular complication associated with the chronic
      endocrine disorder of diabetes mellitus. Angiogenesis is adjudged as a prime
      modulatory event in this complication. The formation of new blood vessels on the
      pre-existing vasculature gives rise to an abundance of anatomical and
      physiological alterations which ultimately results in vision loss. The drastic
      consequences of this complication prompt the obligation of developing effective
      therapies for its cure. The existing therapy mainly includes destructive
      techniques such as laser photocoagulation. Owing to the various drawbacks
      associated with this technique, there is a need to develop alternative therapies
      which could halt the progression of diabetic retinopathy without causing
      considerable damage to the retinal cells. One such possible alternative treatment
      being researched upon is the antiangiogenic therapy. Since angiogenesis is a
      critical event during the progression of this disorder, targeting this event may
      perhaps prove effective in its treatment. Amongst several antiangiogenic agents,
      thalidomide holds a reputable position due to its effectiveness in terminating
      angiogenesis during various pathological conditions. This review focuses on the
      diverse molecular mechanisms proposed to explain the antiangiogenic properties of
      thalidomide and their applicability in diabetic retinopathy.

PMID- 26196303
TI  - Pharmacological activation of AMPK prevents Drp1-mediated mitochondrial fission
      and alleviates endoplasmic reticulum stress-associated endothelial dysfunction.
AB  - BACKGROUND AND PURPOSE: This study aims to investigate whether and how
      pharmacological activation of AMP-activated protein kinase (AMPK) improves
      endothelial function by suppressing mitochondrial ROS-associated endoplasmic
      reticulum stress (ER stress) in the endothelium. Experimental approach Palmitate
      stimulation induced mitochondrial fission and ER stress-associated endothelial
      dysfunction. The effects of AMPK activators salicylate and AICA riboside (AICAR)
      on mitochondrial ROS production, Drp1 phosphorylation, mitochondrial fission, ER
      stress, thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome activation,
      inflammation, cell apoptosis and endothelium-dependent vasodilation were
      observed. Key results "Silencing" of TXNIP by RNA interference inhibited NLRP3
      inflammasome activation in response to ER stress, indicating that TXNIP was a key
      link between ER stress and NLRP3 inflammasome activation. AMPK activators
      salicylate and AICAR prevented ROS-induced mitochondrial fission by enhancing
      dynamin-related protein 1 (Drp1) phosphorylation (Ser 637) and thereby attenuated
      IRE-1alpha and PERK phosphorylation, but their actions were blocked by knockdown
      of AMPK. Salicylate and AICAR reduced TXNIP induction and inhibited NLRP3
      inflammasome activation by reducing NLRP3 and caspase-1 expression, leading to a
      reduction in IL-1beta secretion. As a result, salicylate and AICAR inhibited
      inflammation and reduced cell apoptosis. Meanwhile, salicylate and AICAR enhanced
      eNOS phosphorylation and restored the loss of endothelium-dependent vasodilation
      in the rat aorta. Immunohistochemistry staining showed that AMPK activation
      inhibited ER stress and NLRP3 inflammasome activation in the vascular
      endothelium. CONCLUSION AND IMPLICATIONS: Pharmacological activation of AMPK
      regulated mitochondrial morphology and ameliorated endothelial dysfunction by
      suppression of mitochondrial ROS-associated ER stress and subsequent TXNIP/NLRP3
      inflammasome activation. These findings suggested that regulation of Drp1
      phosphorylation by AMPK activation contributed to suppression of ER stress and
      thus presented a potential therapeutic strategy for AMPK activation in the
      regulation of endothelium homeostasis.

PMID- 26196304
TI  - Multiple quantum filtered (23)Na NMR in the Langendorff perfused mouse heart:
      Ratio of triple/double quantum filtered signals correlates with [Na]i.
AB  - We investigate the potential of multiple quantum filtered (MQF) (23)Na NMR to
      probe intracellular [Na]i in the Langendorff perfused mouse heart. In the
      presence of Tm(DOTP) shift reagent the triple quantum filtered (TQF) signal
      originated largely from the intracellular sodium pool with a 32+/-6% contribution
      of the total TQF signal arising from extracellular sodium, whilst the rank 2
      double-quantum filtered signal (DQF), acquired with a 54.7 degrees  flip-angle
      pulse, originated exclusively from the extracellular sodium pool. Given the
      different cellular origins of the (23)Na MQF signals we propose that the TQF/DQF
      ratio can be used as a semi-quantitative measure of [Na]i in the mouse heart. We
      demonstrate a good correlation of this ratio with [Na]i measured with shift
      reagent at baseline and under conditions of elevated [Na]i. We compare the
      measurements of [Na]i using both shift reagent and TQF/DQF ratio in a cohort of
      wild type mouse hearts and in a transgenic PLM(3SA) mouse expressing a non
      phosphorylatable form of phospholemman, showing a modest but measurable elevation
      of baseline [Na]i. MQF filtered (23)Na NMR is a potentially useful tool for
      studying normal and pathophysiological changes in [Na]i, particularly in
      transgenic mouse models with altered Na regulation. 

PMID- 26196305
TI  - Adiponectin is required for cardiac MEF2 activation during pressure overload
      induced hypertrophy.
AB  - Cardiomyocyte (CM) hypertrophy and increased heart mass in response to pressure
      overload are associated with hyper-activation of the myocyte enhancer factor-2
      (MEF2) family of transcriptional regulators, and concomitant initiation of the
      fetal gene program. Adiponectin, an adipokine that is reduced in individuals with
      obesity and diabetes, has been characterized both as a negative regulator or
      permissive factor in cardiac hypertrophy. We therefore sought to analyze temporal
      regulation of MEF2 activity in response to pressure overload (PO) and changes in
      adiponectin status. To address this we crossed a well characterized transgenic
      MEF2 "sensor" mouse (MEF2-lacZ) with adiponectin null mice (Ad-KO) to create
      compound MEF2 lacZ/Ad-KO mice. Initially, we established that transverse aortic
      banding induced PO in wild-type (WT) mice increased heart mass and CM hypertrophy
      from 1 to 4weeks following surgery, indicated by increased CM diameter and heart
      weight/tibia length ratio. This was associated with cardiac dysfunction
      determined by echocardiography. Hypertrophic changes and dysfunction were
      observed in Ad-KO mice 4weeks following surgery. MEF2 lacZ activity and
      endogenous ANF mRNA levels, used as indicators of hypertrophic gene activation,
      were both robustly increased in WT mice after MTAB but attenuated in the Ad-KO
      background. Furthermore, activation of the pro-hypertrophic molecule p38 was
      increased following MTAB surgery in WT mice, but not in Ad-KO animals, and
      treatment of primary isolated CM with recombinant adiponectin induced p38
      phosphorylation in a time dependent manner. Adiponectin also increased MEF2
      activation in primary cardiomyocytes, an effect attenuated by p38 MAPK
      inhibition. In conclusion, our data indicate that robust hypertrophic MEF2
      activation in the heart in vivo requires a background of adiponectin signaling
      and that adiponectin signaling in primary isolated CM directly enhances MEF2
      activity through activation of p38 MAPK. We conclude that adiponectin is required
      for full induction of cardiomyocyte MEF2 activation, thus contributing to the
      myocardial hypertrophic gene expression program in response to PO. 

PMID- 26196306
TI  - Enhancement of activated sludge dewatering performance by combined composite
      enzymatic lysis and chemical re-flocculation with inorganic coagulants: Kinetics
      of enzymatic reaction and re-flocculation morphology.
AB  - The feasibility of combined process of composite enzymatic treatment and chemical
      flocculation with inorganic salt coagulants was investigated in this study. The
      evolution of extracellular polymeric substances (EPS) distribution, composition
      and morphological properties were analyzed to unravel the sludge conditioning
      mechanism. It was found that sludge filtration performance was deteriorated due
      to release of a large amount of biopolymers after enzymatic treatment. The change
      in EPS followed the pseudo-first-order kinetic equation well under enzymatic
      treatment. The feeding modes of enzymes had a significant influence on sludge
      lysis efficiency under compound enzymes treatment. Alpha amylase + protease was
      more effective in solubilization than other two addition modes (protease + alpha
      amylase or simultaneous addition). The sludge floc re-formed and macromolecule
      biopolymers were effectively removed through coagulation process. At the same
      time, both of filtration rate and cake solid content of sludge treated with
      enzymes were improved with increasing dosage of coagulants, and ferric iron
      (FeCl3) had better performance in sludge dewaterability enhancement than
      polyaluminium chloride (PACl). In addition, sludge filtration property was
      slightly deteriorated, while the cake moisture reduction was favored at the
      optimal dosage of inorganic coagulants. 

PMID- 26196307
TI  - Comparative decay of Catellicoccus marimmalium and enterococci in beach sand and
      seawater.
AB  - Most studies characterize microbial source tracking (MST) target performance
      using sensitivity and specificity metrics. However, it is important to also
      consider the temporal stability of MST targets in relation to regulated microbial
      pollutants. Differences among bacterial target stabilities may lead to erroneous
      conclusions about sources of contamination. The present study evaluates the
      relative stability of MST targets and fecal indicator organisms using the
      gull/pigeon-associated Catellicoccus marimammalium (CAT) marker and enterococci
      (ENT). The decay rates of CAT and ENT measured by culture (cENT) and QPCR (tENT)
      were compared in sand and seawater laboratory microcosms under environmentally
      relevant conditions (subject to tidal wetting versus no wetting in sand, and
      sunlit versus dark conditions in seawater). Bacterial targets were more
      persistent in beach sand than in seawater with decay rates on the order of 0.01
      0.1 per day and 1 to 10 per day, respectively. Targets were more persistent in
      unwetted compared to wetted sand, and dark compared to sunlit seawater. During
      the first 8 days of the sand experiment, the decay rate k of CAT was greater than
      that of cENT. The decay rates of CAT, tENT, and cENT were similar in sand after
      day 8 and in dark seawater. In sunlit seawater, the decay rates were different
      between targets with kcENT > kCAT > ktENT. The decay rates presented here are
      useful for fate and transport models and also inform the use of MST marker
      concentrations to infer ENT sources in the environment. 

PMID- 26196308
TI  - Effects of high nitrogen concentrations on the growth of submersed macrophytes at
      moderate phosphorus concentrations.
AB  - Eutrophication of lakes leading to loss of submersed macrophytes and higher
      turbidity is a worldwide phenomenon, attributed to excessive loading of
      phosphorus (P). However, recently, the role of nitrogen (N) for macrophyte
      recession has received increasing attention. Due to the close relationship
      between N and P loading, disentanglement of the specific effects of these two
      nutrients is often difficult, and some controversy still exists as to the effects
      of N. We studied the effects of N on submersed macrophytes represented by
      Vallisneria natans (Lour.) Hara in pots positioned at three depths (0.4 m, 0.8 m,
      and 1.2 m to form a gradient of underwater light conditions) in 10 large ponds
      having moderate concentrations of P (TP 0.03 +/- 0.04 mg L(-1)) and five targeted
      concentrations of total nitrogen (TN) (0.5, 2, 10, 20, and 100 mg L(-1)), there
      were two ponds for each treatment. To study the potential shading effects of
      other primary producers, we also measured the biomass of phytoplankton (ChlaPhyt)
      and periphyton (ChlaPeri) expressed as chlorophyll a. We found that leaf length,
      leaf mass, and root length of macrophytes declined with increasing concentrations
      of TN and ammonium, while shoot number and root mass did not. All the measured
      growth indices of macrophytes declined significantly with ChlaPhyt, while none
      were significantly related to ChlaPeri. Neither ChlaPhyt nor ChlaPeri were,
      however, significantly negatively related to the various N concentrations. Our
      results indicate that shading by phytoplankton unrelated to the variation in N
      loading and perhaps toxic stress exerted by high nitrogen were responsible for
      the decline in macrophyte growth. 

PMID- 26196309
TI  - Mature ganglioneuroma of the adrenal gland as a new rare cause of visible
      haematuria: A case report & literature review.
AB  - INTRODUCTION: Ganglioneuromas are benign tumours of the sympathetic ganglia and
      the adrenal glands medulla. We describe a case of a fit and well 18 year old
      Caucasian male patient who initially presented to primary care with intermittent
      episodes of painless frank haematuria as well as some non-specific right-sided
      loin pain. PRESENTATION OF CASE: In this 18 year old man, initial ultrasound
      investigations at a 'one stop haematuria' clinic revealed the presence of an
      echogenic solid mass of 120*110*90mm around the upper pole of the right kidney. A
      CT scan of the abdomen proved inconclusive to further determine the aetiology of
      the mass. Following a local multidisciplinary meeting (MDT) an MRI of the abdomen
      was undertaken which confirmed the presence of a large right adrenal mass. A
      biopsy was taken to determine the histology of the mass confirming a mature
      ganglioneuroma. The patient subsequently underwent surgery within 6 weeks of
      having presented to his general practitioner. CONCLUSION AND DISCUSSION: The
      surgery was uncomplicated and excision of the mass was made via a thoraco
      abdominal approach. The patient recovered well post operatively and was
      discharged home within 8 days with outpatient follow-ups organised.

PMID- 26196310
TI  - Arterial injury and pseudoaneurysm formation after lesser trochanter fracture.
AB  - INTRODUCTION: Vascular complications after hip fracture are rare but can be life
      threatening, especially in the elderly and if diagnosed late. PRESENTATION OF THE
      CASE: We report a false aneurysm of the calcified deep femoral artery after hip
      fracture and uneventful stabilization with a gamma nail, in an 85 year old woman.
      Three weeks after surgery there was swelling of the proximal thigh. Ultrasound
      scan revealed a false aneurysm of the deep femoral artery and plain X-ray showed
      a lesser trochanter fragment spiking the calcified deep femoral artery. Open
      repair of the pseudo-aneurysm with a vein patch was performed. DISCUSSION:
      Nowadays the preferred imaging of false aneurysms is by computed tomographic (CT)
      angiography but this involves high radiation and nephrotoxic contrast agents and
      may delay diagnosis. What made this a special case was the post-operative plain X
      ray which showed a displaced fragment of the lesser trochanter spiking the
      calcified deep femoral artery, as confirmed on CT scanning. CONCLUSION: Surgeons
      should pay attention to any displaced bone fragments close to calcified vessels,
      especially in the evaluation of routine x-rays following surgical treatment of
      fractures. This could minimize the potential life-threatening risk of delayed
      diagnosis, especially because it represents a routine image following surgical
      fracture treatments.

PMID- 26196311
TI  - Left Amyand's hernia: An unexpected finding during inguinal hernia surgery.
AB  - INTRODUCTION: Amyand's hernia is a rare finding of the appendix inside an
      inguinal hernia sac with classically estimated incidence of 1%. Most cases are
      found intra-operatively during right-sided inguinal hernia repair. PRESENTATION
      OF CASE: We are reporting a very rare case of left-sided Amyand's hernia. An 81
      year-old man with long standing left inguinal hernia was referred to our surgical
      assessment unit with tender irreducible left inguinal hernia. He was vitally
      stable with no clinical signs of intestinal obstruction. A diagnosis of
      irreducible left inguinal hernia without obstruction was made. Exploration of the
      hernia sac revealed the presence of non-inflamed appendix, caecum and terminal
      ileum. The contents were reduced and a mesh repair was performed with
      satisfactorily outcome. DISCUSSION: The surgical management of Amyand's hernia
      involves appendectomy of inflamed appendix through the inguinal incision together
      with hernia repair. Prophylactic appendectomy is not recommended by most authors
      except in young patients. CONCLUSION: There are less than 20 cases reported in
      the literature describing left-sided Amyand's hernia. Awareness of such very
      unusual condition may help surgeons to be prepared for appropriate management of
      a very usual procedure as inguinal hernia repair.

PMID- 26196312
TI  - Platelet to lymphocyte ratio as a novel indicator of inflammation is correlated
      with the severity of metabolic syndrome: A single center large-scale study.
AB  - Metabolic syndrome (MetS) as a cluster of several cardio-metabolic components is
      rapidly growing public-health problem worldwide and significantly associated with
      poor cardiovascular outcomes. Increased visceral adiposity activates the
      important pathways connecting low-grade chronic inflammation, oxidative stress
      and blood coagulation. Recently, platelet to lymphocyte ratio (PLR) has been
      evidenced as a novel indirect inflammatory marker. Therefore, for the first time,
      we aimed to investigate the association of PLR with both the presence and
      severity of MetS. In this cross-sectional study, a total of 1146 participants
      were enrolled (n = 539 with MetS and n = 607 without MetS). MetS was defined
      according to NCEP-ATP III criteria. MetS (+) group revealed significantly higher
      PLR and C-reactive protein (CRP) levels as compared to MetS (-) group (p < 0.05).
      There was a graded relationship between increasing number of MetS components and
      PLR (p < 0.05). Also, PLR was positively correlated with CRP level (r = 0.163, p
      < 0.001). In multivariate regression analysis, PLR [1.121 (1.113-1.135), p <
      0.001], CRP [1.044 (1.029-1.060), p < 0.001], and age [1.030 (1.017-1.043), p <
      0.001] were remained as independent predictors for the presence of MetS. In
      conclusion, our findings showed that increased PLR was significantly associated
      with both the presence and severity of MetS which was linked to systemic
      inflammation based on the correlation between PLR and CRP. As PLR is an easily
      available, simple and cheap indirect indicator of inflammation, it can be used in
      clinical practice as a predictor of MetS.

PMID- 26196313
TI  - Food preferences and Hg distribution in Chelonia mydas assessed by stable
      isotopes.
AB  - Mercury (Hg) is a highly toxic pollutant that poses in risk several marine
      animals, including green turtles (Chelonia mydas). Green turtles are globally
      endangered sea turtle species that occurs in Brazilian coastal waters as a number
      of life stage classes (i.e., foraging juveniles and nesting adults). We assessed
      total Hg concentrations and isotopic signatures ((13)C and (15)N) in muscle,
      kidney, liver and scute of juvenile green turtles and their food items from two
      foraging grounds with different urban and industrial development. We found
      similar food preferences in specimens from both areas but variable Hg levels in
      tissues reflecting the influence of local Hg backgrounds in food items. Some
      juvenile green turtles from the highly industrialized foraging ground presented
      liver Hg levels among the highest ever reported for this species. Our results
      suggest that juvenile foraging green turtles are exposed to Hg burdens from
      locally anthropogenic activities in coastal areas. 

PMID- 26196315
TI  - Effects of silver sulfide nanomaterials on mycorrhizal colonization of tomato
      plants and soil microbial communities in biosolid-amended soil.
AB  - We investigated effects of Ag2S engineered nanomaterials (ENMs),
      polyvinylpyrrolidone (PVP) coated Ag ENMs (PVP-Ag), and Ag(+) on arbuscular
      mycorrhizal fungi (AMF), their colonization of tomato (Solanum lycopersicum), and
      overall microbial community structure in biosolids-amended soil. Concentration
      dependent uptake was measured in all treatments. Plants exposed to 100 mg kg(-1)
      PVP-Ag ENMs and 100 mg kg(-1) Ag(+) exhibited reduced biomass and greatly reduced
      mycorrhizal colonization. Bacteria, actinomycetes and fungi were inhibited by all
      treatment classes, with the largest reductions measured in 100 mg kg(-1) PVP-Ag
      ENMs and 100 mg kg(-1) Ag(+). Overall, Ag2S ENMs were less toxic to plants, less
      disruptive to plant-mycorrhizal symbiosis, and less inhibitory to the soil
      microbial community than PVP-Ag ENMs or Ag(+). However, significant effects were
      observed at 1 mg kg(-1) Ag2S ENMs, suggesting that the potential exists for
      microbial communities and the ecosystem services they provide to be disrupted by
      environmentally relevant concentrations of Ag2S ENMs. 

PMID- 26196314
TI  - Effects of environmental cadmium and lead exposure on adults neighboring a
      discharge: Evidences of adverse health effects.
AB  - The purpose of the study was to determine Pb and Cd concentrations in humans and
      to assess the effect of co-exposure to these metals on biomarkers of oxidative
      stress and nephrotoxicity. Blood and urine levels of Pb and Cd, oxidative stress
      and urinary renal biomarkers were measured in 77 subjects neighboring a discharge
      and 52 in the control site. Exposed subjects showed significantly higher levels
      of lead and cadmium in blood and urine than the controls. Excessive production of
      reactive oxygen species induced by these metals in exposed subjects conducted to
      a decrease in antioxidant defense system (GPx, Selenium, GSH) and an increase in
      lipid peroxidation (MDA). Moreover, changes in markers of nephrotoxicity (high
      urinary concentrations of total protein, RBP and CC16, as well as GSTalpha and
      LDH increased activities) suggested the occurrence of discrete and early signs of
      impaired renal function for the discharge neighboring population. 

PMID- 26196316
TI  - Effects of landscape heterogeneity on the elevated trace metal concentrations in
      agricultural soils at multiple scales in the Pearl River Delta, South China.
AB  - Based on multiple geo-accumulation indices and correlation and partial redundancy
      analyses, we examined the spatial patterns of agricultural soil contaminations
      for As, Pb, Cd, Cr, and Ni in the Pearl River Delta, South China and their
      relations with landscape heterogeneity at small, medium and large spatial scales.
      We found that the concentrations of trace elements were slightly elevated, and
      most trace metals had a geogenic origin. Landscape variables explained 21-53% of
      the variation of elevated trace metal concentrations with an increasing
      explanatory power from the small to the large scale. The three variable groups
      representing parent materials, distance density characteristics and land use had
      different contributions to the elevated trace metals among scales. Both the
      distance density variables and land use pattern had a stronger influences on
      trace metal concentrations at a small scale than at a larger scale, while the
      parent materials was important at all the scales. 

PMID- 26196318
TI  - Composition and in vitro cytotoxic activities of essential oil of Hedychium
      spicatum from different geographical regions of western Himalaya by principal
      components analysis.
AB  - The rhizome of Hedychium spicatum has been widely used in traditional medicines.
      The present study deals with the evaluation of the cytotoxic potential of rhizome
      essential oils from four different regions of the Western Himalaya (India) along
      with comparative correlation analysis to characterise the bioactive cytotoxic
      component. The essential oils were coded as MHS-1, MHS-2, MHS-3 and MHS-4, and
      characterised using GC-FID and GC-MS. The main volatile compounds identified were
      1,8-cineol, eudesmol, cubenol, spathulenol and alpha-cadinol. In vitro cytotoxic
      activities were assessed against human cancer cell lines such as, the lung
      (A549), colon (DLD-1, SW 620), breast (MCF-7, MDA-MB-231), head and neck (FaDu),
      and cervix (HeLa). MHS-4 is significantly active in comparison to other samples
      against all cancer cell lines. Sample MHS-4 has major proportion of monoterpene
      alcohol mainly 1,8-cineol. Principal components analysis was performed for the
      experimental results and all four samples were clustered according to their
      percentage inhibition at different doses. 

PMID- 26196319
TI  - Definition of a dynamic laparoscopic model for the prediction of incomplete
      cytoreduction in advanced epithelial ovarian cancer: proof of a concept.
AB  - OBJECTIVE: To develop an updated laparoscopy-based model to predict incomplete
      cytoreduction (RT>0) in advanced epithelial ovarian cancer (AEOC), after the
      introduction of upper abdominal surgery (UAS). PATIENTS AND METHODS: The presence
      of omental cake, peritoneal extensive carcinomatosis, diaphragmatic confluent
      carcinomatosis, bowel infiltration, stomach and/or spleen and/or lesser omentum
      infiltration, and superficial liver metastases was evaluated by staging
      laparoscopy (S-LPS) in a consecutive series of 234 women with newly diagnosed
      AEOC, receiving laparotomic PDS after S-LPS. Parameters showing a
      specificity>=75%, PPV>=50%, and NPV>=50% received 1 point score, with an
      additional one point in the presence of an accuracy of >=60% in predicting
      incomplete cytoreduction. The overall discriminating performance of the LPS-PI
      was finally estimated by ROC curve analysis. RESULTS: No-gross residual disease
      at PDS was achieved in 135 cases (57.5%). Among them, UAS was required in 72
      cases (53.3%) for a total of 112 procedures, and around 25% of these patients
      received bowel resection, excluding recto-sigmoid resection. We observed a very
      high overall agreement between S-LPS and laparotomic findings, which ranged from
      74.7% for omental cake to 94.8% for stomach infiltration. At a LPS-PIV>=10 the
      chance of achieving complete PDS was 0, and the risk of unnecessary laparotomy
      was 33.2%. Discriminating performance of LPS-PI was very high (AUC=0.885).
      CONCLUSIONS: S-LPS is confirmed as an accurate tool in the prediction of complete
      PDS in women with AEOC. The updated LPS-PI showed improved discriminating
      performance, with a lower rate of inappropriate laparotomic explorations at the
      established cut-off value of 10.

PMID- 26196321
TI  - Reprint of "Nuclear transport factors: global regulation of mitosis".
AB  - The unexpected repurposing of nuclear transport proteins from their function in
      interphase to an equally vital and very different set of functions in mitosis was
      very surprising. The multi-talented cast when first revealed included the import
      receptors, importin alpha and beta, the small regulatory GTPase RanGTP, and a
      subset of nuclear pore proteins. In this review, we report that recent years have
      revealed new discoveries in each area of this expanding story in vertebrates: (a)
      The cast of nuclear import receptors playing a role in mitotic spindle regulation
      has expanded: both transportin, a nuclear import receptor, and Crm1/Xpo1, an
      export receptor, are involved in different aspects of spindle assembly. Importin
      beta and transportin also regulate nuclear envelope and pore assembly. (b) The
      role of nucleoporins has grown to include recruiting the key microtubule
      nucleator - the gamma-TuRC complex - and the exportin Crm1 to the mitotic
      kinetochores of humans. Together they nucleate microtubule formation from the
      kinetochores toward the centrosomes. (c) New research finds that the original
      importin beta/RanGTP team have been further co-opted by evolution to help
      regulate other cellular and organismal activities, ranging from the actual
      positioning of the spindle within the cell perimeter, to regulation of a newly
      discovered spindle microtubule branching activity, to regulation of the
      interaction of microtubule structures with specific actin structures. (d) Lastly,
      because of the multitudinous roles of karyopherins throughout the cell cycle, a
      recent large push toward testing their potential as chemotherapeutic targets has
      begun to yield burgeoning progress in the clinic.

PMID- 26196320
TI  - Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce
      significant apoptosis via cytochrome c release and suppress growth of castration
      resistant prostate cancer xenografts in vivo.
AB  - Galeterone (Gal) is a first-in-class multi-target oral small molecule that will
      soon enter pivotal phase III clinical trials in castration resistant prostate
      cancer (CRPC) patients. Gal disrupts androgen receptor (AR) signaling via
      inhibition of CYP17, AR antagonism and AR degradation. Resistance to current
      therapy is attributed to up-regulation of full-length AR (fAR), splice variants
      AR (AR-Vs) and AR mutations. The effects of gal and VNPT55 were analyzed on f-AR
      and AR-Vs (AR-V7/ARv567es) in LNCaP, CWR22Rv1 and DU145 (transfected with AR-Vs)
      human PC cells in vitro and CRPC tumor xenografts. Galeterone/VNPT55 decreased
      fAR/AR-V7 mRNA levels and implicates Mdm2/CHIP enhanced ubiquitination of
      posttranslational modified receptors, targeting them for proteasomal degradation.
      Gal and VNPT55 also induced significant apoptosis in PC cells via increased
      Bax/Bcl2 ratio, cytochrome-c release with concomitant cleavage of caspase 3 and
      PARP. More importantly, gal and VNPT55 exhibited strong in vivo anti-CRPC
      activities, with no apparent host toxicities. This study demonstrate that gal and
      VNPT55 utilize cell-based mechanisms to deplete both fAR and AR-Vs. Importantly,
      the preclinical activity profiles, including profound apoptotic induction and
      inhibition of CRPC xenografts suggest that these agents offer considerable
      promise as new therapeutics for patients with CRPC and those resistant to current
      therapy. 

PMID- 26196322
TI  - Genome Sequence and Architecture of the Tobacco Downy Mildew Pathogen Peronospora
      tabacina.
AB  - Peronospora tabacina is an obligate biotrophic oomycete that causes blue mold or
      downy mildew on tobacco (Nicotiana tabacum). It is an economically important
      disease occurring frequently in tobacco-growing regions worldwide. We sequenced
      and characterized the genomes of two P. tabacina isolates and mined them for
      pathogenicity-related proteins and effector-encoding genes. De novo assembly of
      the genomes using Illumina reads resulted in 4,016 (63.1 Mb, N50 = 79 kb) and
      3,245 (55.3 Mb, N50 = 61 kb) scaffolds for isolates 968-J2 and 968-S26,
      respectively, with an estimated genome size of 68 Mb. The mitochondrial genome
      has a similar size (approximately 43 kb) and structure to those of other
      oomycetes, plus several minor unique features. Repetitive elements, primarily
      retrotransposons, make up approximately 24% of the nuclear genome. Approximately
      18,000 protein-coding gene models were predicted. Mining the secretome revealed
      approximately 120 candidate RxLR, six CRN (candidate effectors that elicit
      crinkling and necrosis), and 61 WY domain-containing proteins. Candidate RxLR
      effectors were shown to be predominantly undergoing diversifying selection, with
      approximately 57% located in variable gene-sparse regions of the genome. Aligning
      the P. tabacina genome to Hyaloperonospora arabidopsidis and Phytophthora spp.
      revealed a high level of synteny. Blocks of synteny show gene inversions and
      instances of expansion in intergenic regions. Extensive rearrangements of the
      gene-rich genomic regions do not appear to have occurred during the evolution of
      these highly variable pathogens. These assemblies provide the basis for studies
      of virulence in this and other downy mildew pathogens. 

PMID- 26196323
TI  - Expanding the p53 regulatory network: LncRNAs take up the challenge.
AB  - Long noncoding RNAs (lncRNAs) are rapidly emerging as important regulators of
      gene expression in a wide variety of physiological and pathological cellular
      processes. In particular, a number of studies revealed that some lncRNAs
      participate in the p53 pathway, the unquestioned protagonist of tumor suppressor
      response. Indeed, several lncRNAs are not only part of the large pool of genes
      coordinated by p53 transcription factor, but are also required by p53 to fine
      tune its response and to fully accomplish its tumor suppressor program. In this
      review we will discuss the current and fast growing knowledge about the
      contribution of lncRNAs to the complexity of the p53 network, the different
      mechanisms by which they affect gene regulation in this context, and their
      involvement in cancer. The incipient impact of lncRNAs in the p53 biological
      response may encourage the development of therapies and diagnostic methods
      focused on these noncoding molecules. This article is part of a Special Issue
      entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and
      Dr. Shinichi Nakagawa. 

PMID- 26196324
TI  - Mucosal vaccination by the intranasal route. Nose-associated lymphoid tissue
      (NALT)-Structure, function and species differences.
AB  - The advantage of mucosal vaccination in viral and bacterial infections in
      different age groups is of enormous clinical relevance. The advantages and
      potential hazards of intranasal vaccination have always to be considered. The
      intranasal route for vaccination is very successful for some antigens. Specific
      adjuvants are necessary. In the nose of rodents there is a structured lymphoid
      tissue (nose-associated lymphoid tissue (NALT)). This abbreviation should not be
      used for nasopharynx-associated lymphoid tissue, as this includes parts of the
      tonsils. In children lymphoid tissue is more dispersed in the nose and not
      concentrated at the bottom of the dorsal nose ducts as in rodents. There are no
      data on organized lymphoid tissue in the nose of adults. In NALT of rodents there
      is a unique structure of adhesion molecule expression; the postnatal development
      and the different composition of T and B lymphocytes in comparison with Peyer's
      patches document the uniqueness of this lymphoid organ. There is also a mucosa in
      the nose with antigen-presenting dendritic cells. Thus, it is often unclear
      whether intranasal vaccination is initiated via NALT or the diffuse nasal mucosa.
      There are still many open questions e. g., which adjuvant is necessary for a
      specific virus, bacterium or other allergen, how many doses are critical for an
      effective nasal vaccination. Species differences are of major importance when
      extrapolating results from rodents to humans. 

PMID- 26196326
TI  - Influenza vaccination in India: Challenges for universal adoption.

PMID- 26196325
TI  - Restricted replication of the live attenuated influenza A virus vaccine during
      infection of primary differentiated human nasal epithelial cells.
AB  - Live Attenuated Influenza Vaccine (LAIV) strains are associated with cold
      adapted, temperature sensitive and attenuated phenotypes that have been studied
      in non-human or immortalized cell cultures as well as in animal models. Using a
      primary, differentiated human nasal epithelial cell (hNEC) culture system we
      compared the replication kinetics, levels of cell-associated viral proteins and
      virus particle release during infection with LAIV or the corresponding wild type
      (WT) influenza viruses. At both 33  degrees C and 37  degrees C, seasonal
      influenza virus and an antigenically matched LAIV replicated to similar titers in
      MDCK cells but seasonal influenza virus replicated to higher titers than LAIV in
      hNEC cultures, suggesting a greater restriction of LAIV replication in hNEC
      cultures. Despite the disparity in infectious virus production, the supernatants
      from H1N1 and LAIV infected hNEC cultures had equivalent amounts of viral
      proteins and hemagglutination titers, suggesting the formation of non-infectious
      virus particles by LAIV in hNEC cultures.

PMID- 26196327
TI  - Attitudes toward influenza vaccination improvement strategies in Veterans Affairs
      health care workers providing care for patients with spinal cord injuries and
      disorders: Acceptability of a declination form program.
AB  - BACKGROUND: Influenza is associated with high rates of morbidity and mortality.
      The most effective way to prevent influenza or severe consequences from the
      illness is vaccination, and key organizations recommend that all health care
      workers (HCWs) be vaccinated annually for influenza. Recent literature suggests
      declination form programs (DFPs) are a useful approach to improve HCW influenza
      vaccination rates. OBJECTIVE: To understand support for and beliefs about use of
      an influenza vaccination DFP, and how this is associated with HCW beliefs about
      other influenza vaccination improvement strategies. METHODS: Data were collected
      via a cross-sectional mailed national survey. Participants included HCWs
      providing care to Veterans with spinal cord injuries and disorders (SCI/D) from
      23 nationwide Veterans Affairs facilities. Analyses included bivariate analyses
      of outcomes among DFP supporters vs. non-supporters. RESULTS: Of the HCW
      respondents, 67% reported that they would support a DFP at their facility. A
      greater proportion of HCWs who support (vs. do not support) DFPs reported
      receiving an annual influenza vaccination (86.35% vs. 65.81%, p<0.0001).
      Similarly, a significantly greater proportion of HCWs who support DFPs (vs. do
      not support) reported willingness to receive an influenza vaccination (83.79% vs.
      61.48%, p<0.0001) and nasal spray influenza vaccination (45.75% vs. 32.50%,
      p=0.0156). HCWs who support DFPs were more likely to report a great deal of
      influence in almost all typical vaccination improvement campaign strategies on
      their decision to be vaccinated, and less likely to endorse commonly provided
      reasons for refusing vaccination as valid. CONCLUSION: More HCWs who support DFPs
      engage in important influenza-related health behaviors (e.g., vaccination), and
      support other influenza vaccination improvement strategies. Facilities may
      benefit from implementing DFPs as part of their vaccination improvement campaign.
      Support for DFPs among HCWs is high, suggesting implementing this as a policy
      would be well-received by staff, and potentially effective in increasing HCW
      influenza vaccination.

PMID- 26196328
TI  - An advanced fragment analysis-based individualized subtype classification of
      pediatric acute lymphoblastic leukemia.
AB  - Pediatric acute lymphoblastic leukemia (ALL) is the most common neoplasm and one
      of the primary causes of death in children. Its treatment is highly dependent on
      the correct classification of subtype. Previously, we developed a microarray
      based subtype classifier based on the relative expression levels of 62 marker
      genes, which can predict 7 different ALL subtypes with an accuracy as high as 97%
      in completely independent samples. Because the classifier is based on gene
      expression rank values rather than actual values, the classifier enables an
      individualized diagnosis, without the need to reference the background
      distribution of the marker genes in a large number of other samples, and also
      enables cross platform application. Here, we demonstrate that the classifier can
      be extended from a microarray-based technology to a multiplex qPCR-based
      technology using the same set of marker genes as the advanced fragment analysis
      (AFA). Compared to microarray assays, the new assay system makes the convenient,
      low cost and individualized subtype diagnosis of pediatric ALL a reality and is
      clinically applicable, particularly in developing countries. 

PMID- 26196329
TI  - Computed tomography perfusion evaluation after extracranial-intracranial bypass
      surgery.
AB  - OBJECTIVE: Perfusion imaging is increasingly used for postoperative evaluation of
      extracranial to intracranial (EC-IC) bypass surgery. Altered hemodynamics and
      delayed arrival of the contrast agent in the area fed by the bypass can influence
      perfusion measurement. We compared perfusion asymmetry obtained with different
      algorithms in EC-IC bypass surgery patients. METHODS: We retrospectively
      identified all patients evaluated with computed tomography perfusion (CTP)
      between May 2007 and May 2011 after EC-IC bypass surgery at our institution. CTP
      images were analyzed with three perfusion algorithms that differ among their
      ability to anticipate for delayed arrival time of contrast material: the delay
      sensitive first-moment mean transit time (fMTT), the semi-delay-sensitive
      standard singular value decomposition (sSVD) and the delay-insensitive block
      circulant SVD (bSVD). The interhemispheric difference in bolus arrival time
      (DeltaBAT) was determined to confirm altered hemodynamics. Interhemispheric
      asymmetry in perfusion values (mean transit time (MTT) difference, cerebral blood
      flow (CBF) ratio and cerebral blood volume (CBV) ratio) was compared between the
      three algorithms. Presence of a new infarct in the treated hemisphere was
      evaluated on follow-up imaging and perfusion asymmetry was compared between
      patients with and without infarction. RESULTS: Twenty-two patients were included.
      The median interhemispheric difference in DeltaBAT was 0.98 s. The median MTT
      difference was significantly smaller when calculated with the delay-insensitive
      algorithm than with the other algorithms (0.44 s versus 0.90 s and 0.93 s,
      p<0.01). The CBF ratio was similar for all algorithms (111.98 versus 112.59 and
      112.60). The CBV ratio was similar for all algorithms (113.20 versus 111.95 and
      113.97). There was a significant difference in MTT asymmetry between patients
      with and without infarction with the delay-insensitive algorithm only (1.57 s
      versus 0.38 s, p=0.04). CONCLUSION: In patients with EC-IC bypass surgery, delay
      sensitive algorithms showed larger MTT asymmetry than delay-insensitive
      algorithms. Furthermore, only the delay-insensitive method seems to differentiate
      between patients with and without infarction on follow-up.

PMID- 26196331
TI  - Measles Vaccination Coverage and Cases among Vaccinated Persons.

PMID- 26196330
TI  - On palms, bugs, and Chagas disease in the Americas.
AB  - Palms are ubiquitous across Neotropical landscapes, from pristine forests or
      savannahs to large cities. Although palms provide useful ecosystem services, they
      also offer suitable habitat for triatomines and for Trypanosoma cruzi mammalian
      hosts. Wild triatomines often invade houses by flying from nearby palms,
      potentially leading to new cases of human Chagas disease. Understanding and
      predicting triatomine-palm associations and palm infestation probabilities is
      important for enhancing Chagas disease prevention in areas where palm-associated
      vectors transmit T. cruzi. We present a comprehensive overview of palm
      infestation by triatomines in the Americas, combining a thorough reanalysis of
      our published and unpublished records with an in-depth review of the literature.
      We use site-occupancy modeling (SOM) to examine infestation in 3590 palms sampled
      with non-destructive methods, and standard statistics to describe and compare
      infestation in 2940 palms sampled by felling-and-dissection. Thirty-eight palm
      species (18 genera) have been reported to be infested by ~39 triatomine species
      (10 genera) from the USA to Argentina. Overall infestation varied from 49.1-55.3%
      (SOM) to 62.6-66.1% (dissection), with important heterogeneities among sub
      regions and particularly among palm species. Large palms with complex crowns
      (e.g., Attalea butyracea, Acrocomia aculeata) and some medium-crowned palms
      (e.g., Copernicia, Butia) are often infested; in slender, small-crowned palms
      (e.g., Euterpe) triatomines associate with vertebrate nests. Palm infestation
      tends to be higher in rural settings, but urban palms can also be infested. Most
      Rhodnius species are probably true palm specialists, whereas Psammolestes,
      Eratyrus, Cavernicola, Panstrongylus, Triatoma, Alberprosenia, and some
      Bolboderini seem to use palms opportunistically. Palms provide extensive habitat
      for enzootic T. cruzi cycles and a critical link between wild cycles and
      transmission to humans. Unless effective means to reduce contact between people
      and palm-living triatomines are devised, palms will contribute to maintaining
      long-term and widespread, albeit possibly low-intensity, transmission of human
      Chagas disease. 

PMID- 26196332
TI  - Anti-inflammatory Effects of Perioperative Dexmedetomidine Administered as an
      Adjunct to General Anesthesia: A Meta-analysis.
AB  - The aim of this meta-analysis is to examine the effects of dexmedetomidine on
      serum inflammatory markers when administered perioperatively. We searched
      multiple electronic databases for relevant research papers, and carried out meta
      analyses of weighted mean differences and interpreted in the light of statistical
      heterogeneity (I(2)). Fifteen RCTs recruiting 641 patients were included.
      Dexmedetomidine treatment significantly decreased interleukin-6 (IL-6), IL-8 and
      tumor necrosis factor-alpha (TNF-alpha) levels with mean differences [95% CI] in
      the changes from baseline between dexmedetomidine treated and controls of -25.14
      [-35.29, -15.00]; P < 0.00001 (for IL-6), -5.69 [-10.77, -0.60]; P < 0.04 (for IL
      8), and -20.30 [-30.93, -9.67]; P < 0.0002 (for TNF-alpha) immediately after
      surgery; and -41.55 [-57.41, -25.70]; P < 0.00001 (IL-6), -6.46 [-10.83, -2.08];
      P < 0.005 (IL-8), and -14.67 [-22.61, -6.73]; P < 0.0003 (TNF-alpha) on
      postoperative day 1 (random effects). IL-10 levels were found to increase
      significantly a day after surgery (8.33 [3.31, 13.36]; P = 0.001). Subgroup
      analyses did not reveal significant differences. In conclusion, perioperative
      adjunctive use of dexmedetomidine substantially decreases serum IL-6, IL-8 and
      TNF-alpha levels. 

PMID- 26196333
TI  - Caged ligands to study the role of intracellular GPCRs.
AB  - In addition to cell surface membranes, numerous G protein-coupled receptors
      (GPCRs) are located on intracellular membranes including the nuclear envelope.
      Although the role of numerous GPCRs at the cell surface has been well
      characterized, the physiological function of these same receptors located on
      intracellular membranes remains to be determined. Here, we employ a novel caged
      Ang-II analog, cAng-II, to compare the effects of the activation of cell surface
      versus intracellular angiotensin receptors in intact cardiomyocytes. When added
      extracellularly to HEK 293 cells, Ang-II and photolysed cAng-II increased ERK1/2
      phosphorylation (via AT1R) and cGMP production (AT2R). In contrast unphotolysed
      cAng-II did not. Cellular uptake of cAng-II was 6-fold greater than that of Ang
      II and comparable to the HIV TAT(48-60) peptide. Intracellular photolysis of cAng
      II induced an increase in nucleoplasmic Ca(2+) ([Ca(2+)]n) that was greater than
      that induced by extracellular application of Ang-II. We conclude that cell
      permeable ligands that can access intracellular GPCRs may evoke responses
      distinct from those with access restricted to the same receptor located on the
      cell surface. 

PMID- 26196335
TI  - The natural selection of altruistic traits.
AB  - Proponents of the standard evolutionary biology paradigm explain human "altruism"
      in terms of either nepotism or strict reciprocity. On that basis our underlying
      nature is reduced to a function of inclusive fitness: human nature has to be
      totally selfish or nepotistic. Proposed here are three possible paths to giving
      costly aid to nonrelatives, paths that are controversial because they involve
      assumed pleiotropic effects or group selection. One path is pleiotropic subsidies
      that help to extend nepotistic helping behavior from close family to
      nonrelatives. Another is "warfare"-if and only if warfare recurred in the
      Paleolithic. The third and most plausible hypothesis is based on the morally
      based egalitarian syndrome of prehistoric hunter-gatherers, which reduced
      phenotypic variation at the within-group level, increased it at the between-group
      level, and drastically curtailed the advantages of free riders. In an analysis
      consistent with the fundamental tenets of evolutionary biology, these three paths
      are evaluated as explanations for the evolutionary development of a rather
      complicated human social nature. 

PMID- 26196334
TI  - Shifts in bacterial community composition associated with increased carbon
      cycling in a mosaic of phytoplankton blooms.
AB  - Marine microbes have a pivotal role in the marine biogeochemical cycle of carbon,
      because they regulate the turnover of dissolved organic matter (DOM), one of the
      largest carbon reservoirs on Earth. Microbial communities and DOM are both highly
      diverse components of the ocean system, yet the role of microbial diversity for
      carbon processing remains thus far poorly understood. We report here results from
      an exploration of a mosaic of phytoplankton blooms induced by large-scale natural
      iron fertilization in the Southern Ocean. We show that in this unique ecosystem
      where concentrations of DOM are lowest in the global ocean, a patchwork of blooms
      is associated with diverse and distinct bacterial communities. By using on-board
      continuous cultures, we identify preferences in the degradation of DOM of
      different reactivity for taxa associated with contrasting blooms. We used the
      spatial and temporal variability provided by this natural laboratory to
      demonstrate that the magnitude of bacterial production is linked to the extent of
      compositional changes. Our results suggest that partitioning of the DOM resource
      could be a mechanism that structures bacterial communities with a positive
      feedback on carbon cycling. Our study, focused on bacterial carbon processing,
      highlights the potential role of diversity as a driving force for the cycling of
      biogeochemical elements. 

PMID- 26196336
TI  - Complex societies : The evolutionary origins of a crude superorganism.
AB  - The complexity of human societies of the past few thousand years rivals that of
      social insect societies. We hypothesize that two sets of social "instincts"
      underpin and constrain the evolution of complex societies. One set is ancient and
      shared with other social primate species, and one is derived and unique to our
      lineage. The latter evolved by the late Pleistocene, and led to the evolution of
      institutions of intermediate complexity in acephalous societies. The institutions
      of complex societies often conflict with our social instincts. The complex
      societies of the past few thousand years can function only because cultural
      evolution has created effective "work-arounds" to manage such instincts. We
      describe a series of work-arounds and use the data on the relative effectiveness
      of WWII armies to test the work-around hypothesis. 

PMID- 26196337
TI  - Multilevel selection and the social transmission of behavior.
AB  - Many evolutionary models assume that behaviors are caused directly by genes. An
      implication is that behavioral uniformity should be found only in groups that are
      genetically uniform. Yet, the members of human social groups often behave in a
      uniform fashion, despite the fact that they are genetically diverse. Behavioral
      uniformity can occur through a variety of psychological mechanisms and social
      processes, such as imitation, consensus decision making, or the imposition of
      social norms. We present a series of models in which genes code for social
      transmission rules, which in turn govern the behaviors that are adopted.
      Transmission rules can evolve in randomly formed groups that concentrate
      phenotypic variation at the between-group level, favoring the evolution of
      altruistic behaviors and other group-advantageous traits. In addition, a direct
      bias toward adopting altruistic behaviors can evolve. Our models begin to show
      how group selection can be a strong force in human evolution, despite the absence
      of extreme genetic variation among groups. 

PMID- 26196338
TI  - Multilevel selection, cooperation, and altruism : Reflections on unto others: The
      evolution and psychology of unselfish behavior.
AB  - Unto Others (Sober and Wilson 1998) shows how the general principles of Multi
      Level Selection (MLS) theory apply to selection at multiple levels of the
      biological hierarchy. It also argues for the existence of "genuine" evolutionary
      and psychological altruism. The authors' views on altruism do not follow
      logically from principles of MLS, and their failure do disentangle these two
      themes undermines their otherwise excellent presentation of MLS theory. Rebuttal
      of the view that human nature is completely selfish depends not on the prevalence
      of altruism but on the importance of group-advantageous traits that benefit both
      self and other group members without necessarily inflicting direct costs on
      outsiders. 

PMID- 26196339
TI  - ["Foreign physicians are more often failed" does not apply to all groups].

PMID- 26196340
TI  - [The curse of the impact factor].

PMID- 26196341
TI  - [Not Available].

PMID- 26196342
TI  - Hydrogen/Deuterium Exchange and Molecular Dynamics Analysis of Amyloid Fibrils
      Formed by a D69K Charge-Pair Mutant of Human Apolipoprotein C-II.
AB  - Plasma apolipoproteins form amphipathic alpha helices in lipid environments but
      in the lipid-free state show a high propensity to form beta structure and self
      associate into amyloid fibrils. The widespread occurrence of apolipoproteins in
      amyloid plaques suggests disease-related roles, specifically in atherosclerosis.
      To reconcile the dual abilities of apolipoproteins to form either alpha helices
      or cross-beta sheet structures, we examined fibrils formed by human
      apolipoprotein C-II (apoC-II). A structural model for apoC-II fibrils shows a
      cross-beta core with parallel beta strands, including a buried K30-D69 charge
      pair. We investigated the effect of abolishing this charge pair in mutant D69K
      apoC-II. Fluorescence studies indicated more rapid fibril formation and less
      solvent accessibility of tryptophan (W26) in D69K apoC-II fibrils than in wild
      type (WT) fibrils. X-ray diffraction data of aligned D69K apoC-II fibrils yielded
      a typical cross-beta structure with increased beta sheet spacing compared to that
      of WT fibrils. Hydrogen/deuterium (H/D) exchange patterns were similar for D69K
      apoC-II fibrils compared to WT fibrils, albeit with an overall reduction in the
      level of slow H/D exchange, particularly around residues 29-32. Molecular
      dynamics simulations indicated reduced beta strand content for a model D69K apoC
      II tetramer compared to the WT tetramer and confirmed an expansion of the cross
      beta spacing that contributed to the formation of a stable charge pair between
      K69 and E27. The results highlight the importance of charge-pair interactions
      within the apoC-II fibril core, which together with numerous salt bridges in the
      flexible connecting loop play a major role in the ability of lipid-free apoC-II
      to form stable cross-beta fibrils.

PMID- 26196343
TI  - Application of an Advanced Image-Based Virtual Monoenergetic Reconstruction of
      Dual Source Dual-Energy CT Data at Low keV Increases Image Quality for Routine
      Pancreas Imaging.
AB  - PURPOSE: To compare image quality on contrast-enhanced dual-energy computed
      tomography (DECT) during the pancreatic parenchymal phase of pancreatic masses
      between linearly-blended simulated 120 kVp images (routine) and advanced image
      based virtual monoenergetic reconstructions at 55 keV. METHODS: This was a
      retrospective evaluation of 24 nonconsecutive adults found to have a focal
      pancreatic mass on a multiphasic abdominal dual-source DECT (12 adenocarcinoma, 5
      neuroendocrine, 7 cystic tumors). For pancreatic-parenchymal phase images,
      subjects had routine and 55 keV images reconstructed at the time of clinical
      evaluation. Quantitative evaluation by contrast-to-noise ratio and qualitative
      evaluations of image quality by (1) direct comparison of image pairs (preference)
      and (2) blinded assessment of image quality measures based on Likert scores were
      performed. RESULTS: Mean patient weight was 205.8 +/- 26.6 lbs. Mean pancreatic
      lesion contrast-to-noise ratio was significantly higher at 55 keV (6.8 +/- 4.1)
      compared to the routine image series (5.8 +/- 3.8; P = 0.0002). All 3 readers
      preferred the 55-keV images over routine blended images in 70.1% to 95.8% of
      cases. No significant differences were observed for subjective sharpness of the
      mass, visualization of internal mass structures, or image noise. CONCLUSIONS: Use
      of a single advanced image-based virtual monoenergetic reconstruction at 55 keV
      in pancreatic DECT showed improved objective image quality and reader preference
      compared to routine images. As this image reconstruction can be incorporated into
      the scan protocol, this technique should be considered for routine clinical use.

PMID- 26196344
TI  - Cardiac Hydatid Cysts: Computed Tomography and Magnetic Resonance Imaging
      Findings of the 5 Cases.
AB  - OBJECTIVE: In this article, we aimed to review the computed tomography (CT) and
      magnetic resonance imaging (MRI) findings of cardiac hydatid disease.
      CONCLUSIONS: Regarding the diagnostic work-up of cardiac hydatid disease, CT and
      MRI are complimentary techniques. Whereas CT effectively depicts wall
      calcifications, MRI reveals the exact anatomic location and nature of the
      internal and external structures and is the technique used for the early
      diagnosis, assessment, and follow-up of patients with cardiac hydatid disease.

PMID- 26196345
TI  - Comparison of Free-Breathing With Navigator-Triggered Technique in Diffusion
      Weighted Imaging for Evaluation of Small Hepatocellular Carcinoma: Effect on
      Image Quality and Intravoxel Incoherent Motion Parameters.
AB  - OBJECTIVE: To evaluate the effect on image quality and intravoxel incoherent
      motion (IVIM) parameters of small hepatocellular carcinoma (HCC) from choice of
      either free-breathing (FB) or navigator-triggered (NT) diffusion-weighted (DW)
      imaging. METHODS: Thirty patients with 37 small HCCs underwent IVIM DW imaging
      using 12 b values (0-800 s/mm) with 2 sequences: NT, FB. A biexponential analysis
      with the Bayesian method yielded true diffusion coefficient (D), pseudodiffusion
      coefficient (D*), and perfusion fraction (f) in small HCCs and liver parenchyma.
      Apparent diffusion coefficient (ADC) was also calculated. The acquisition time
      and image quality scores were assessed for 2 sequences. Independent sample t test
      was used to compare image quality, signal intensity ratio, IVIM parameters, and
      ADC values between the 2 sequences; reproducibility of IVIM parameters, and ADC
      values between 2 sequences was assessed with the Bland-Altman method (BA-LA).
      RESULTS: Image quality with NT sequence was superior to that with FB acquisition
      (P = 0.02). The mean acquisition time for FB scheme was shorter than that of NT
      sequence (6 minutes 14 seconds vs 10 minutes 21 seconds +/- 10 seconds P < 0.01).
      The signal intensity ratio of small HCCs did not vary significantly between the 2
      sequences. The ADC and IVIM parameters from the 2 sequences show no significant
      difference. Reproducibility of D*and f parameters in small HCC was poor (BA-LA:
      95% confidence interval, -180.8% to 189.2% for D* and -133.8% to 174.9% for f). A
      moderate reproducibility of D and ADC parameters was observed (BA-LA: 95%
      confidence interval, -83.5% to 76.8% for D and -74.4% to 88.2% for ADC) between
      the 2 sequences. CONCLUSIONS: The NT DW imaging technique offers no advantage in
      IVIM parameters measurements of small HCC except better image quality, whereas FB
      technique offers greater confidence in fitted diffusion parameters for matched
      acquisition periods.

PMID- 26196346
TI  - Prediction of Reperfusion-Associated Hemorrhagic Transformation Using Dynamic
      Contrast-Enhanced Imaging in a Rat Stroke Model.
AB  - BACKGROUND AND PURPOSE: Reperfusion-associated hemorrhagic transformation (HT) is
      an important complication of recanalization therapy. A method to identify stroke
      victims that may undergo HT will improve the patient selection and safety of this
      treatment. In this study, we determined the relationship between timing of
      reperfusion and the frequency and severity of HT, and whether very early dynamic
      contrast-enhanced (DCE) imaging predicts the occurrence of reperfusion-associated
      HT in a model of experimental stroke. METHODS: Intraluminal suture occlusion of
      the middle cerebral artery was used to produce transient ischemia in male Sprague
      Dawley rats (n = 50). Reperfusion was performed by withdrawal of the occluding
      filament after 3 (n = 10), 4 (n = 10), 5 (n = 10), 6 (n = 10), or 7 (n = 10)
      hours. Magnetic resonance imaging studies were performed before reperfusion using
      DCE, susceptibility-weighted imaging, diffusion-weighted imaging, and T2- and T1
      weighted imaging. Follow-up magnetic resonance imaging and histological studies
      were performed at 24 hours. RESULTS: Hemorrhagic transformation occurred by 24
      hours after injury in 8 of 50 animals. The HT rate increased with prolonged
      ischemic duration. All animals exhibiting acute blood-brain barrier (BBB)
      perturbation subsequently developed HT by 24 hours. Statistically significant
      differences in the BBB permeability parameters (P < 0.05) between the HT group
      and non-HT group were detected by DCE imaging. There were also statistically
      significant differences (P < 0.05) between the HT area and adjacent HT area.
      Among the permeability parameters, subcortex rK was the most sensitive and
      specific predictor of HT. CONCLUSIONS: The results suggest that the use of
      quantitative BBB measurements may further improve early prediction and
      identification of HT. The DCE parameters were the sensitive early independent
      predictor of reperfusion-associated HT.

PMID- 26196347
TI  - Computed Tomography Number Measurement Consistency Under Different Beam Hardening
      Conditions: Comparison Between Dual-Energy Spectral Computed Tomography and
      Conventional Computed Tomography Imaging in Phantom Experiment.
AB  - PURPOSE: To compare computed tomography (CT) number measurement consistency under
      different beam hardening conditions in phantom experiment between dual-energy
      spectral CT and conventional CT imaging. MATERIALS AND METHODS: A phantom with 8
      cells in periphery region and 1 cell in central region were used. The 8
      conditioning tubes in the periphery region were filled with 1 of the 3 iodine
      solutions to simulate different beam hardening conditions: 0 for no beam
      hardening (NBH), 20 mg/mL for weak beam hardening (WBH) and 50 mg/mL for severe
      beam hardening (SBH) condition. Test tube filled with 0, 0.1, 0.5, 1, 2, 5, 10,
      20, and 50 mg/mL iodine solution was placed in the central cell alternately. The
      phantom was scanned with conventional CT mode with 80, 100, 120, and 140 kVp and
      dual energy spectral CT mode. For spectral CT, 11 monochromatic image sets from
      40 to 140 keV with interval of 10 keV were reconstructed. The CT number shift
      caused by beam hardening was evaluated by measuring the CT number difference
      (DeltaCT) with and without beam hardening, with the following formulas:
      DeltaCTWBH = |CTWBH - CTNBH| and DeltaCTSBH = |CTSBH - CTNBH|. Data were compared
      with 1-way analysis of variance. RESULTS: Under both WBH and SBH conditions, the
      CT number shifts in all monochromatic image sets were less than those for
      polychromatic images (all P < 0.001). Under WBH condition, the maximum CT number
      shift was less than 6 Hounsfield units for monochromatic spectral CT images of
      all energy levels; under SBH condition, only monochromatic images at 70 keV and
      80 keV had CT number shift less than 6 HU. CONCLUSION: Dual energy spectral CT
      imaging provided more accurate CT number measurement than conventional CT under
      various beam hardening conditions. The optimal keV level for monochromatic
      spectral CT images with the most accurate CT number measurement depends on the
      severities of beam hardening condition.

PMID- 26196348
TI  - Correction: Consistent global structures of complex RNA states through
      multidimensional chemical mapping.

PMID- 26196349
TI  - Evidence-based Health Informatics: How Do We Know What We Know?
AB  - BACKGROUND: Health IT is expected to have a positive impact on the quality and
      efficiency of health care. But reports on negative impact and patient harm
      continue to emerge. The obligation of health informatics is to make sure that
      health IT solutions provide as much benefit with as few negative side effects as
      possible. To achieve this, health informatics as a discipline must be able to
      learn, both from its successes as well as from its failures. OBJECTIVES: To
      present motivation, vision, and history of evidence-based health informatics, and
      to discuss achievements, challenges, and needs for action. METHODS: Reflections
      on scientific literature and on own experiences. RESULTS: Eight challenges on the
      way towards evidence-based health informatics are identified and discussed:
      quality of studies; publication bias; reporting quality; availability of
      publications; systematic reviews and meta-analysis; training of health IT
      evaluation experts; translation of evidence into health practice; and post-market
      surveillance. Identified needs for action comprise: establish health IT study
      registers; increase the quality of publications; develop a taxonomy for health IT
      systems; improve indexing of published health IT evaluation papers; move from
      meta-analysis to meta-summaries; include health IT evaluation competencies in
      curricula; develop evidence-based implementation frameworks; and establish post
      marketing surveillance for health IT. CONCLUSIONS: There has been some progress,
      but evidence-based health informatics is still in its infancy. Building evidence
      in health informatics is our obligation if we consider medical informatics a
      scientific discipline.

PMID- 26196351
TI  - Histone Deacetylase Inhibition and IkappaB Kinase/Nuclear Factor-kappaB Blockade
      Ameliorate Microvascular Proinflammatory Responses Associated With Hemorrhagic
      Shock/Resuscitation in Mice.
AB  - OBJECTIVE: To investigate the consequences of histone deacetylase inhibition by
      histone deacetylase inhibitor valproic acid and IkappaB kinase/nuclear factor
      kappaB signaling blockade by IkappaB kinase inhibitor BAY11-7082 on
      (microvascular) endothelial cell behavior in vitro as well as in mice subjected
      to hemorrhagic shock/resuscitation in vivo. DESIGN: Prospective, randomized
      laboratory investigation using an established mouse model of hemorrhagic shock.
      SETTING: Research laboratory at university teaching hospital. SUBJECTS:
      Endothelial cells and C57BL/6 male mice. INTERVENTIONS: Endothelial cells were
      incubated with tumor necrosis factor-alpha in the absence or presence of valproic
      acid or BAY11-7082 in vitro. Mice were subjected to hemorrhagic shock by blood
      withdrawn until the mean arterial pressure of 30 mm Hg and maintained at this
      pressure for 90 minutes. At 90 minutes, subgroups of mice were resuscitated with
      4% human albumin in the absence or presence of vehicle, valproic acid (300 MUg/g
      body weight) or BAY11-7082 (400 MUg per mouse). Mice were killed 1 hour and 4
      hours after resuscitation. MEASUREMENTS AND MAIN RESULTS: Valproic acid and BAY11
      7082 selectively diminished tumor necrosis factor-alpha-induced endothelial
      proinflammatory activation in vitro. In vivo, both systemic and local
      inflammatory responses were significantly induced by hemorrhagic
      shock/resuscitation. The decreased histone acetylation in kidneys after
      hemorrhagic shock/resuscitation was restored by valproic acid treatment. In
      glomerular endothelial cells, the nuclear translocation of nuclear factor-kappaB,
      which was induced by hemorrhagic shock/resuscitation, was eliminated by BAY11
      7082 treatment while enhanced in the presence of valproic acid. Both valproic
      acid and BAY11-7082 significantly attenuated the hemorrhagic shock/resuscitation
      induced protein expression of endothelial cell adhesion molecules E-selectin and
      vascular cell adhesion molecule-1 in the microvasculature of kidneys and liver,
      although messenger RNA expression levels of these molecules analyzed in whole
      organ lysates of kidneys, lungs, and liver were not extensively affected. The
      reduced protein expression of adhesion molecules was paralleled by diminishing
      the adhesion/transmigration of neutrophils in kidneys and liver after hemorrhagic
      shock/resuscitation. CONCLUSION: Suppression of histone deacetylase activity and
      blockade of IkappaB kinase/nuclear factor-kappaB signaling during resuscitation
      ameliorate microvascular endothelial proinflammatory responses in organs in mice
      after hemorrhagic shock.

PMID- 26196350
TI  - Raised Proinflammatory Cytokine Production Within Cerebrospinal Fluid Precedes
      Fever Onset in Patients With Neurosurgery-Associated Bacterial Meningitis.
AB  - OBJECTIVE: The objective of the present study was to determine whether selective
      inflammatory cytokine concentrations within cerebrospinal fluid are useful
      markers for the differential diagnosis of aseptic and bacterial meningitis within
      neurosurgical patients. DESIGN: Prospective, open-label, observational, cohort
      study. SETTING: Neurosurgical ICU, Chang Gung Memorial Hospital. PATIENTS: Thirty
      two consecutive neurosurgical patients who had postoperative fever following
      external ventricular drain insertion for the treatment of brain injury underwent
      serial cerebrospinal fluid cytokine analysis pre and post fever to determine the
      value of such markers in ascertaining the differential diagnosis of meningitis.
      INTERVENTION: Cerebrospinal fluid samples were collected on the day of fever
      onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis
      factor-alpha, interleukin-1beta, interleukin-6, interleukin-8, transforming
      growth factor-beta, and procalcitonin were subsequently analyzed using enzyme
      linked immunosorbent assay analysis techniques. MEASUREMENT AND MAIN RESULTS:
      Inflammatory marker levels were compared among febrile aseptic, bacterial, and
      nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over
      time. Significant increases in cerebrospinal fluid tumor necrosis factor -alpha,
      interleukin-1beta, interleukin-6, and interleukin-8 levels were observed within
      patients with bacterial meningitis at fever onset, which was not evident in
      aseptic or nonmeningitis patients. Furthermore, significant increases in
      cerebrospinal fluid tumor necrosis factor-alpha, interleukin-1beta, interleukin
      6, and interleukin-8 levels were detected as early as 4 days prior to fever onset
      within patients with bacterial meningitis when compared with both aseptic and
      nonmeningitis groups. Interestingly, procalcitonin was only significantly
      increased in patients with bacterial meningitis on the fourth day post fever.
      CONCLUSION: The present study suggests that raised cerebrospinal fluid tumor
      necrosis factor -alpha, interleukin-1beta, and interleukin-8 in a temporal manner
      may indicate early bacterial meningitis development in neurosurgical patients,
      enabling earlier diagnostic certainty and improved patient outcomes.

PMID- 26196352
TI  - The Involvement of Danger-Associated Molecular Patterns in the Development of
      Immunoparalysis in Cardiac Arrest Patients.
AB  - OBJECTIVES: After cardiac arrest, patients are highly vulnerable toward
      infections, possibly due to a suppressed state of the immune system called
      "immunoparalysis." We investigated if immunoparalysis develops following cardiac
      arrest and whether the release of danger-associated molecular patterns could be
      involved. DESIGN: Observational study. SETTING: ICU of a university medical
      center. PATIENTS: Fourteen post-cardiac arrest patients treated with mild
      therapeutic hypothermia for 24 hours and 11 control subjects. MEASUREMENTS AND
      MAIN RESULTS: Plasma cytokines showed highest levels within 24 hours after
      cardiac arrest and decreased during the next 2 days. By contrast, ex vivo
      production of cytokines interleukin-6, tumor necrosis factor-alpha, and
      interleukin-10 by lipopolysaccharide-stimulated leukocytes was severely impaired
      compared with control subjects, with most profound effects observed at day 0, and
      only partially recovering afterward. Compared with incubation at 37 degrees C,
      incubation at 32 degrees C resulted in higher interleukin-6 and lower interleukin
      10 production by lipopolysaccharide-stimulated leukocytes of control subjects,
      but not of patients. Plasma nuclear DNA, used as a marker for general danger
      associated molecular pattern release, and the specific danger-associated
      molecular patterns (EN-RAGE and heat shock protein 70) were substantially higher
      in patients at days 0 and 1 compared with control subjects. Furthermore, plasma
      heat shock protein 70 levels were negatively correlated with ex vivo production
      of inflammatory mediators interleukin-6, tumor necrosis factor-alpha, and
      interleukin-10. Extracellular newly identified receptor for advanced glycation
      end products-binding protein levels only showed a significant negative
      correlation with ex vivo production of interleukin-6 and tumor necrosis factor
      alpha and a borderline significant inverse correlation with interleukin-10. No
      significant correlations were observed between plasma nuclear DNA levels and ex
      vivo cytokine production. INTERVENTIONS: None. CONCLUSIONS: Release of danger
      associated molecular patterns during the first days after cardiac arrest is
      associated with the development of immunoparalysis. This could explain the
      increased susceptibility toward infections in cardiac arrest patients.

PMID- 26196353
TI  - Critical Care for Multiple Organ Failure Secondary to Ebola Virus Disease in the
      United States.
AB  - OBJECTIVE: This report describes three patients with Ebola virus disease who were
      treated in the United States and developed for severe critical illness and
      multiple organ failure secondary to Ebola virus infection. The patients received
      mechanical ventilation, renal replacement therapy, invasive monitoring,
      vasopressor support, and investigational therapies for Ebola virus disease. DATA
      SOURCES: Patient medical records from three tertiary care centers (Emory
      University Hospital, University of Nebraska Medical Center, and Texas Health
      Presbyterian Dallas Hospital). STUDY SELECTION: Not applicable. DATA EXTRACTION:
      Not applicable. DATA SYNTHESIS: Not applicable. CONCLUSION: In the severe form,
      patients with Ebola virus disease may require life-sustaining therapy, including
      mechanical ventilation and renal replacement therapy. In conjunction with other
      reported cases, this series suggests that respiratory and renal failure may occur
      in severe Ebola virus disease, especially in patients burdened with high viral
      loads. Ebola virus disease complicated by multiple organ failure can be
      survivable with the application of advanced life support measures. This
      collective, multicenter experience is presented with the hope that it may inform
      future treatment of patients with Ebola virus disease requiring critical care
      treatment.

PMID- 26196354
TI  - Ultrarapid Induction of Hypothermia Using Continuous Automated Peritoneal Lavage
      With Ice-Cold Fluids: Final Results of the Cooling for Cardiac Arrest or Acute ST
      Elevation Myocardial Infarction Trial.
AB  - OBJECTIVES: Hypothermia (32-34  degrees C) can mitigate ischemic brain injury,
      and some evidence suggests that it can reduce infarct size in acute myocardial
      infarction and acute ischemic stroke. For some indications, speed of cooling may
      be crucial in determining efficacy. We performed a multicenter prospective
      intervention study to test an ultrarapid cooling technology, the Velomedix
      Automated Peritoneal Lavage System using ice-cold fluids continuously circulating
      through the peritoneal cavity to rapidly induce and maintain hypothermia in
      comatose patients after cardiac arrest and a small number of awake patients with
      acute myocardial infarction. DESIGN: Multicenter prospective intervention study.
      SETTING: Intensive care- and coronary care units of multiple tertiary referral
      centers. MEASUREMENTS AND MAIN RESULTS: Access to the peritoneal cavity was
      gained using a modified blunt dilating instrument, followed by catheter
      placement. Patients were cooled to a temperature of 32.5  degrees C, maintained
      for 24 hours (cardiac arrest) or 3 hours (acute myocardial infarction) followed
      by controlled rewarming. Forty-nine patients were enrolled, and 46 patients
      completed treatment. One placement was unsuccessful (abdominal wall not
      breached), two patients were ultimately not cooled, and only safety data are
      reported. Average catheter insertion time was 2.3 minutes. Mean time to
      temperature less than 33  degrees C was 10.4 minutes (average cooling rate, 14 
      degrees C/hr). Median infarct size in patients who had coronary interventions was
      16% of LV. No cases of stent thrombosis occurred. Survival in cardiac arrest
      patients with initial rhythm of ventricular tachycardia/ventricular fibrillation
      was 56%, of whom 82 had a complete neurologic recovery. This compares favorably
      to outcomes from previous studies. CONCLUSION: Automated peritoneal lavage system
      is a safe and ultrarapid method to induce and maintain hypothermia, which appears
      feasible in cardiac arrest patients and awake patients with acute myocardial
      infarction. The shivering response appeared to be delayed and much reduced with
      this technology, diminishing metabolic disorders associated with cooling and
      minimizing sedation requirement. Our data suggest that ultrarapid cooling could
      prevent subtle neurologic damage compared with slower cooling. This will need to
      be confirmed in direct comparative studies.

PMID- 26196355
TI  - Highly Regioselective Indoline Synthesis under Nickel/Photoredox Dual Catalysis.
AB  - Nickel/photoredox catalysis is used to synthesize indolines in one step from
      iodoacetanilides and alkenes. Very high regioselectivity for 3-substituted
      indoline products is obtained for both aliphatic and styrenyl olefins.
      Mechanistic investigations indicate that oxidation to Ni(III) is necessary to
      perform the difficult C-N bond-forming reductive elimination, producing a Ni(I)
      complex, which in turn is reduced to Ni(0). This process serves to further
      demonstrate the utility of photoredox catalysts as controlled single electron
      transfer agents in multioxidation state nickel catalysis. 

PMID- 26196356
TI  - A Facile FeCl3/I2-Catalyzed Aerobic Oxidative Coupling Reaction: Synthesis of
      Tetrasubstituted Imidazoles from Amidines and Chalcones.
AB  - A facile and efficient route for the synthesis of tetrasubstituted imidazoles
      from amidines and chalcones via FeCl3/I2-catalyzed aerobic oxidative coupling has
      been developed. This new strategy is featured by high regioselectivity and
      yields, good functional group tolerance, and mild reaction conditions. 

PMID- 26196357
TI  - Development of an Immunoassay for the Detection of the Phenylpyrazole Insecticide
      Fipronil.
AB  - Phenylpyrazole insecticides such as fipronil have been used as replacements for
      organophosphates. The wide application of fipronil raises concern about
      environmental contamination and risk for fish, birds, and other nontargeted
      beings as well as human health. A sensitive, competitive indirect heterologous
      enzyme-linked immunosorbent assay (ELISA) was developed. Antibodies with
      different specificities to fipronil and its metabolites were produced. Two ELISAs
      having IC50 values of 0.58 +/- 0.06 and 2.6 +/- 0.4 ng/mL were developed. Design
      of different haptens and coating antigens resulted in two assays with distinct
      cross-reactivity patterns for structurally related compounds: 96, 38, and 101%
      versus 39, 1.4, and 25% for fipronil-sulfide, fipronil-detrifluoromethylsulfonyl,
      and fipronil-desulfinyl, respectively. Performance of the immunoassays was
      demonstrated by a recovery study from spiked water and human serum and urine
      matrices, giving recovery values in the range of 85-111% for different
      concentrations. The assays demonstrated good correlation in fipronil recovery
      with conventional LC-MS/MS analysis. The generic assay 2265 has the sensitivity
      to measure fipronil and its analogs in serum at levels relevant for exposure
      monitoring. The assays were used to analyze human urine samples obtained from
      exposure studies and serum samples from rats treated with a fipronil-containing
      diet.

PMID- 26196359
TI  - Fabrication of hierarchical ZnO/CdS heterostructured nanocomposites for enhanced
      hydrogen evolution from solar water splitting.
AB  - ZnO/CdS heterostructured nanocomposites were fabricated with enhanced light
      harvesting capability and photostability using sequential sonochemical and
      hydrothermal methods from ZnO rods and particles. Interestingly, in the composite
      made up of CdS sensitized ZnO rods, both ZnO and CdS exist in the hexagonal
      wurtzite form with different morphologies. On the other hand, in the composite
      made up of CdS sensitized ZnO particles, ZnO exists in the hexagonal wurtzite
      form, whereas CdS in the cubic form but with a similar morphology. The
      synthesized photocatalysts under simulated solar irradiation exhibited hydrogen
      evolution rates of 870 and 1007 MUmol h(-1) g(-1) for the ZnO rod/CdS and ZnO
      nanoparticle/CdS composites, respectively, compared to the native ZnO (40 MUmol
      h(-1) g(-1) for rods and 154 MUmol h(-1) g(-1) for particles) and CdS (208 MUmol
      h(-1) g(-1)) structures. The apparent quantum yield of CdS was only 1.2%, whereas
      the composites exhibited much higher quantum yields of 4.9% and 5.7%. Our results
      confirmed that the morphology of the host matrix ZnO played a crucial role in
      forming ZnO/CdS heterostructures with improved interface for the direct Z-scheme
      mechanism with enhanced hydrogen evolution efficiency. 

PMID- 26196358
TI  - Transmission Models of Historical Ebola Outbreaks.
AB  - To guide the collection of data under emergent epidemic conditions, we reviewed
      compartmental models of historical Ebola outbreaks to determine their
      implications and limitations. We identified future modeling directions and
      propose that the minimal epidemiologic dataset for Ebola model construction
      comprises duration of incubation period and symptomatic period, distribution of
      secondary cases by infection setting, and compliance with intervention
      recommendations. 

PMID- 26196360
TI  - Enterobius Vermicularis as a Cause of Intestinal Occlusion: How To Avoid
      Unnecessary Surgery.
AB  - Enterobius vermicularis may cause infections of the gastrointestinal tract and
      occurs approximately in 4% to 28% of children worldwide. It is most common in
      children aged 5 to 14 years.The most commonly reported symptoms are pruritus in
      the perianal region, abdominal pain, urinary tract infection, insomnia,
      irritability, salpingitis, and appendicitis, whereas intestinal obstruction is a
      very rare but would be considered to perform the right instrumental examination
      avoiding unnecessary surgical exploration.We report a case of an 8-year-old boy
      with an intestinal occlusion due to a colonic intussusception by Enterobius
      vermicularis managed conservatively. 

PMID- 26196361
TI  - A Rare Cause of Metabolic Acidosis: Fatal Transdermal Methanol Intoxication in an
      Infant.
AB  - Oral methanol intoxication is common, but dermal intoxication is rare. We report
      a previously healthy 19-month-old female infant admitted to the emergency
      department (ED) with vomiting and tonic-clonic seizure. On physical examination,
      she was comatose and presented signs of decompensated shock with Kussmaul
      breathing. Her left thigh was edematous, with purple coloration. Methanol
      intoxication was suspected due to high anion gap metabolic acidosis (pH, 6.89;
      HCO3, <3 meq/L) and exposure to spirit-soaked bandages (%96 methanol) for 24
      hours and 3 days. The patient's serum methanol level was 20.4 mg/dL. She was
      treated with fomepizole and continuous venovenous hemodialysis (CVVHD) in the
      pediatric intensive care unit, and methanol levels decreased to 0 mg/dL after 12
      hours. During follow-up, massive edema and subarachnoid hemorrhage in the
      occipital lobe were detected by computed tomography of the brain. The patient
      died after 7 days.Although methanol intoxication occurs predominantly in adults,
      it must be considered in children with high-anion gap metabolic acidosis. This
      case report demonstrates that fatal transdermal methanol intoxication can occur
      in children, and it is the second report in the English literature of transdermal
      methanol intoxication in an infant. 

PMID- 26196362
TI  - Evaluation of Safety and Cost-Effectiveness of the Low Risk Ankle Rule in One of
      Europe's Busiest Pediatric Emergency Departments.
AB  - OBJECTIVES: Low Risk Ankle Rule (LRAR) has 100% sensitivity for identifying
      clinically important pediatric ankle fractures (high-risk injuries) and has the
      potential to safely reduce imaging by approximately 60%. This study investigates
      the safety and cost-effectiveness of this rule in our institution. METHODS: All
      patients triaged during July and August 2013 with an "ankle injury" had a
      retrospective clinical notes and radiology report review. Data were recorded
      using Excel and tests of significance, chi test. RESULTS: One hundred twenty-one
      patients were included. Of these, 65 were female and 56 were male (no significant
      difference in sex, P = 0.41). Mean age was 9.95 years. Seventy-eight (64%) had
      LRAR positive examinations. Of these, 77 (98.7%) had an x-ray and 12 (15%) had
      fractures. Of those with fractures, none had high-risk injuries.Eighteen (100%)
      of the doctors in our ED felt that a clinical decision rule would be of use
      within the department. Only 8 (44%) had heard of the LRAR, and of these, only 4
      (50%) would be confident to implement the LRAR. Forty-four (88%) of parents felt
      that an x-ray is required in the diagnosis of ankle injuries in children, and 41
      (82%) would want to know whether their child had an ankle sprain or a low-risk
      fracture even if the management was not different. CONCLUSIONS: By implementing
      the LRAR in our institution, we could reduce ankle x-rays by 64%. This would
      offer a significant reduction in radiation exposure to a radiosensitive
      population. Estimated costs of an ankle x-ray and interpretation are Euro 47
      ($65), thus with more than 800 carried out per year in The Children's University
      Hospital, a potential annual saving is Euro 25,000 ($34,500).

PMID- 26196363
TI  - An Evaluation of the Accuracy and Necessity of Fracture Clinic Referrals in a
      Busy Pediatric Emergency Department.
AB  - OBJECTIVES: Injuries account for approximately 18% of all pediatric emergency
      department presentations. Of these, a significant amount will have fractures that
      will require orthopedic management usually in the orthopedic fracture clinic. Our
      aim was to assess the accuracy and necessity of fracture clinic referrals from
      our emergency department and to suggest an approach that might safely reduce the
      referral numbers. METHODS: All fracture clinic referrals from Temple Street
      Emergency Department in August 2013 were retrospectively audited. RESULTS: There
      were 339 fracture clinic referrals in August 2013. Of these, 213 (63%) had
      fractures as reported by a consultant radiologist. One hundred twenty-six (37%)
      had no fracture confirmed, and of these, 24 (19%) had no fracture seen in the
      emergency department but were referred as clinically fractured. Thirty-three
      (10%) of the 339 were buckle fractures of the wrist. There were 21 (6.2%) finger
      injuries referred. Of ankle injuries referred to fracture clinic (n = 43), 14
      (33%) were confirmed Salter-Harris 1 or 2 or avulsion fractures of the lateral
      malleolus and 16 (37%) were suspected Salter-Harris 1 or 2 fractures of the
      lateral malleolus. CONCLUSIONS: Through education and policy change such as the
      establishment of an Advanced Nurse Practioner (ANP)-led clinic or a virtual
      clinic within our emergency department, we could safely and efficiently reduce
      orthopedic fracture clinic referrals by more than 30%.

PMID- 26196364
TI  - Distraction Injury of the Thoracic Spine With Spinal Cord Transection and
      Vascular Injury in a 5-Week-Old Infant Boy: A Case of Child Physical Abuse.
AB  - Distraction injury of the spine with spinal cord transection and adjacent
      vascular injury is rarely described in the setting of child physical abuse. We
      report a 5-week-old infant boy who sustained these injuries after an abusive
      event. The clinical presentation, imaging findings, and recommended evaluation
      modalities are discussed. An overview of pediatric spinal column and vascular
      injuries secondary to physical abuse is given.

PMID- 26196366
TI  - Variation in Computed Tomography Use for Evaluation of Head Injury in a Pediatric
      Emergency Department.
AB  - OBJECTIVES: Recent research has shown significant variation in rates of computed
      tomography (CT) use among pediatric hospital emergency departments (ED) for
      evaluation of head injured children. We examined the rates of CT use by
      individual ED attending physicians for evaluation of head injured children in a
      pediatric hospital ED. METHODS: We used an administrative database to identify
      children younger than 18 years evaluated for head injury from January 2011
      through March 2013 at our children's hospital ED, staffed by pediatric emergency
      medicine (PEM) fellowship trained physicians and pediatricians. We excluded
      encounters with trauma team activation or previous head CT performed elsewhere.
      We excluded physicians whose patient volume was less than 1 standard deviation
      below the group mean. RESULTS: After exclusions, we evaluated 5340 encounters for
      head injury by 27 ED attending physicians. For individual physicians, CT rates
      ranged from 12.4% to 37.3%, with a mean group rate of 28.4%. Individual PEM
      physician CT rates ranged from 18.9% to 37.3%, versus 12.4% to 31.8% for
      pediatricians. Of the 1518 encounters in which CT was done, 128 (8.4%) had a
      traumatic brain injury on CT, and 125 (8.2%) had a simple skull fracture without
      traumatic brain injury on CT. Patient factors associated with CT use included age
      younger than 2 years, higher triage acuity, arrival time of 10:00 PM to 6:00 AM,
      hospital admission, and evaluation by a PEM physician. CONCLUSIONS: Physicians at
      our pediatric hospital ED varied in the use of CT for the evaluation of head
      injured children.

PMID- 26196367
TI  - Effect of increase in birth weight in a newborn on hip ultrasonography.
AB  - Exposure to the pressure experienced by higher birth weight babies during the
      intrauterine period might cause hip dysplasia. The aim of this study is to
      determine the effect of birth weight in newborns on hip ultrasonography when the
      paternal and maternal risk factors are excluded. A total of 701 babies born at 38
      42 gestational weeks were included in the study. Hip ultrasonography was
      performed within 7 days following birth using the Graf technique in the babies
      without risk factors for developmental dysplasia of the hip. Images obtained were
      controlled with respect to conformity to the Graf method and angular measurements
      were performed. According to the alpha and beta angle values obtained, type 1A
      and 1B hips were categorized as mature; type 2A hips were categorized as
      immature; and type 2C, D, 3A, 3B, and 4 hips were categorized as pathological
      hips. The results obtained were analyzed for the effect of birth weight on the
      angular values and hip typing. The birth weight of the babies was 338,488 +/-
      48,241 g (2030-6124 g). It was determined that the birth weight had no effect on
      the values of alpha and beta angles in the male babies (P=0.21, 0.76). It was
      determined that increasing birth weight decreased the alpha angle value (P=0.001)
      and caused no difference in the beta angle value (P=0.057) in the female babies.
      It was found that birth weight had no effect on hip typing in both female and
      male babies (P=0.060, 0.22). Increases in birth weights caused decreases in
      ultrasonographic alpha angles only in female babies.

PMID- 26196368
TI  - Single forearm radius and ulna asymmetric lengthening in multiple cartilaginous
      exostoses: a case report and a long-term follow-up.
AB  - We describe one case of forearm deformity in a patient affected by multiple
      cartilaginous exostoses - also known as the forearm 'candy stick deformity'.
      Surgical treatment usually focuses on the correction of the wrist deformity
      without correcting the forearm shortening, the latter not being given the same
      consideration as lower limb shortening. In the presented case, radius and ulna
      corticotomies were performed and distal forearm deformity and shortening were
      corrected by two independent monoaxial external fixators, with full
      pronosupination. It is our belief that simultaneous treatment of forearm
      shortening and deformity not only results in an improved clinical and functional
      result but also provides significant psychological benefit. We recommend a long
      term follow-up. 

PMID- 26196369
TI  - The distal radius and ulna classification in assessing skeletal maturity: a
      simplified scheme and reliability analysis.
AB  - The aim of this study is to simplify the distal radius and ulna classification
      for practical use and to test its reliability. This was a prospective single
      center study of patients with juvenile and adolescent idiopathic scoliosis. Left
      hand radiographs were retrieved for measurements by three examiners. Reliability
      analysis was carried out by intraclass correlation. 34 females and 16 males were
      recruited, mean age 12.7 years (+/-SD 1.7). The grades varied from R4-R11 to U1
      U9. There was strong to near-perfect intraclass correlation. This study concludes
      that the simplified distal radius and ulna classification is a reliable tool for
      assessment of skeletal maturity.

PMID- 26196370
TI  - Synergistic local drug delivery in a piglet model of ischemic osteonecrosis: a
      preliminary study.
AB  - A locally injectable system sequentially delivering an antiresorptive drug
      (clodronate) followed by an osteogenic agent (simvastatin) was hypothesized to
      improve femoral head microarchitecture, size, and shape compared with untreated
      or partial treatment groups in an established piglet osteonecrosis model. After 6
      weeks, the clodronate+simvastatin treatment resulted in no collapse, microCT
      measurements and epiphyseal quotients within 10% of control, normal
      microstructure, and healthy histology. All other groups exhibited collapse, lower
      epiphyseal quotients and total femoral head volumes (P<0.05), and abnormal
      histology. This pilot study provides evidence of synergistic antiresorptive and
      osteogenic activities, which may prevent femoral head collapse in Perthes
      disease. 

PMID- 26196371
TI  - Sacral fatigue fractures in children with sacral spina bifida occulta.
AB  - In this report, we present two cases of 9-year-old children with spina bifida
      occulta (SBO) of the sacrum, who were diagnosed with sacral fatigue fractures. In
      both patients, MRI showed a linear signal void and high signal in sacral ala on
      the short tau inversion recovery sequence. Sacral SBO at the same level of the
      sacral fracture was observed in each patient on computed tomography images. These
      lesions healed with rest. This is the first literature reporting cases with
      sacral stress fractures who had SBO at the same level of fracture. 

PMID- 26196372
TI  - Catalytic Behavior of Different Sizes of Dendrimer-Encapsulated Au(n)
      Nanoparticles in the Oxidative Degradation of Morin with H2O2.
AB  - Different sizes of icosahedral-like dendrimer-encapsulated Au nanoparticles (Au55
      and Au147-DENs) were prepared in the presence of generation 6 amine-terminated
      dendrimers (G6-PAMAM-NH2) as a template. The synthesis is carried out by the
      complexation of a Au metal precursor (AuHCI4) with the tertiary amine groups
      within the dendrimer framework. The addition of excess reducing agent, NaBH4,
      results in the formation of Au nanoparticles encapsulated within the dendrimer
      cavities. The as-prepared catalysts were characterized using UV-visible (UV-vis)
      spectroscopy, high-resolution transmission electron microscopy (HRTEM), energy
      dispersive X-ray analysis (EDX), and Fourier transform infrared (FTIR). The
      average sizes of Au55- and Au147-DENs were determined to be 1.7 +/- 0.4 and 2.0
      +/- 0.3 nm, respectively. The catalytic activity of these Au-DEN catalysts was
      evaluated in the oxidative decomposition of morin by H2O2. Since morin has a
      maximum absorption band at lambda 410 nm at pH 10, this catalyzed oxidation
      process was monitored by time-resolved UV-vis spectroscopy. The catalytic
      activities of these two catalysts were compared by fitting the kinetic data to
      the Langmuir-Hinshelwood model. This model allows the determination of adsorption
      constants of both morin (K(morin)) and H2O2 (K(H2O2)) on the catalyst surface. A
      full kinetic study for this Au-DEN-catalyzed oxidative degradation of morin is
      reported.

PMID- 26196373
TI  - DNA-Based Self-Assembly of Fluorescent Nanodiamonds.
AB  - As a step toward deterministic and scalable assembly of ordered spin arrays we
      here demonstrate a bottom-up approach to position fluorescent nanodiamonds (NDs)
      with nanometer precision on DNA origami structures. We have realized a reliable
      and broadly applicable surface modification strategy that results in DNA
      functionalized and perfectly dispersed NDs that were then self-assembled in
      predefined geometries. With optical studies we show that the fluorescence
      properties of the nitrogen-vacancy color centers in NDs are preserved during
      surface modification and DNA assembly. As this method allows the nanoscale
      arrangement of fluorescent NDs together with other optically active components in
      complex geometries, applications based on self-assembled spin lattices or plasmon
      enhanced spin sensors as well as improved fluorescent labeling for bioimaging
      could be envisioned. 

PMID- 26196374
TI  - Improved Methanol Barrier Property of Nafion Hybrid Membrane by Incorporating
      Nanofibrous Interlayer Self-Immobilized with High Level of Phosphotungstic Acid.
AB  - High level of phosphotungstic acid (PWA) was self-immobilized on electrospun
      nylon nanofiberous sheet to fabricate highly selective methanol barrier layer for
      sandwich structured proton conducting membranes. Simple tuning for the assembly
      conditions of central layer and thickness of outer Nafion layers allowed
      obtaining different composite membranes with superior methanol barrier properties
      (namely, P=3.59*10(-8) cm2 s(-1)) coupled with proton conductivities reaching
      58.6 mS cm(-1) at 30  degrees C. Comparable activation energy for proton
      transport and more than 20 times higher selectivity than Nafion 115 confirm the
      effectiveness of the central layer and resulting membranes for application in
      direct methanol fuel cells (DMFCs). When tested in DMFC single cell, the
      performance of hybrid membrane was far better than Nafion 115 especially at
      higher methanol concentrations.

PMID- 26196375
TI  - Epidemiology of lupus: an update.
AB  - PURPOSE OF REVIEW: Recent interest in lupus has expanded various efforts to
      better define its population burden. The Centers for Disease Control and
      Prevention coordinated National Lupus Registries that advance our epidemiologic
      understanding of and methodological approach to lupus. RECENT FINDINGS: More
      accurate estimates of incidence and prevalence of lupus in the United States have
      shown significant burden among racial/ethnic minority groups. These efforts
      underscore the need to better coordinate future studies, particularly as it
      relates to case definition. SUMMARY: These efforts confirm the significant burden
      of systemic lupus erythematosus, particularly in younger minority populations.
      Experience from these studies could also inform other surveillance efforts in
      lupus, as well as other medical conditions for which similar methodologic
      challenges exist.

PMID- 26196376
TI  - Newly recognized Mendelian disorders with rheumatic manifestations.
AB  - PURPOSE OF REVIEW: We review newly discovered monogenic immune-dysregulatory
      disorders that were reported in Pubmed over the last year. RECENT FINDINGS:
      Fourteen novel monogenic immune-dysregulatory disorders that present with innate
      and acquired/adaptive immune dysregulation and inflammatory clinical phenotypes
      were identified. These include autosomal-dominant gain-of function mutations in
      viral innate immune sensors or their adaptors, TMEM173/STING IFIH1/MDA5 and
      DDX58/RIG-I that cause complex clinical syndromes distinct from IL-1-mediated
      diseases and present with a chronic type I interferon (IFN Type I) signature in
      peripheral blood. Gain-of-function mutations in NLRC4 add a novel inflammasome
      disorder associated with predisposition to macrophage-activation syndrome and
      highly elevated IL-18 levels. Mutations in ADA2, TRNT1 and COPA, AP1S3, and
      TNFRSF11A cause complex syndromes; loss-of-function mutations in enzymes and
      molecules are linked to the generation of 'cellular stress' and the release of
      inflammatory mediators that likely cause the inflammatory disease manifestations.
      A monogenic form of systemic-onset juvenile idiopathic arthritis is caused by
      homozygous mutations in LACC1. Lastly, mutations in PRKDC (recessive), STAT3,
      CTLA4, and PIK3R1 (all dominant) lead to impaired central and peripheral T-cell
      tolerance and present with variable disease manifestations of immunodeficiency
      and immune dysregulation/autoimmunity. SUMMARY: A number of novel monogenic
      diseases that present with innate and/or acquired immune dysregulation reveal
      novel immune pathways that cause human inflammatory diseases and suggest
      potential novel targets for treatment.

PMID- 26196377
TI  - Broad Negative Thermal Expansion Operation-Temperature Window Achieved by
      Adjusting Fe-Fe Magnetic Exchange Coupling in La(Fe,Si)13 Compounds.
AB  - Cubic La(Fe,Si)13-based compounds have been recently developed as promising
      negative thermal expansion(NTE) materials, but the narrow NTE operation
      temperature window(~110 K) restricts their actual applications. In this work, we
      demonstrate that the NTE operation-temperature window of LaFe(13-x)Si(x) can be
      significantly broadened by adjusting Fe-Fe magnetic exchange coupling as x ranges
      from 2.8 to 3.1. In particular, the NTE operation-temperature window of
      LaFe10.1Si2.9 is extended to 220 K. More attractively, the coefficients of
      thermal expansion of LaFe10.0Si3.0 and LaFe9.9Si3.1 are homogeneous in the NTE
      operation-temperature range of about 200 K, which is much valuable for the
      stability of fabricating devices. The further experimental characterizations
      combined with first-principles studies reveal that the tetragonal phase is
      gradually introduced into the cubic phase as the Si content increases, hence
      modifies the Fe-Fe interatomic distance. The reduction of the overall Fe-Fe
      magnetic exchange interactions contributes to the broadness of NTE operation
      temperature window for LaFe(13-x)Si(x).

PMID- 26196378
TI  - Genomic Assays for Identification of Chikungunya Virus in Blood Donors, Puerto
      Rico, 2014.
AB  - A newly developed transcription-mediated amplification assay was used to detect
      chikungunya virus infection in 3 of 557 asymptomatic donors (0.54%) from Puerto
      Rico during the 2014-2015 Caribbean epidemic. Viral detection was confirmed by
      using PCR, microarray, and next-generation sequencing. Molecular clock analysis
      dated the emergence of the Puerto Rico strains to early 2013. 

PMID- 26196379
TI  - Lack of presynaptic interaction between glucocorticoid and CB1 cannabinoid
      receptors in GABA- and glutamatergic terminals in the frontal cortex of
      laboratory rodents.
AB  - Corticosteroid and endocannabinoid actions converge on prefrontocortical circuits
      associated with neuropsychiatric illnesses. Corticosteroids can also modulate
      forebrain synapses by using endocannabinoid effector systems. Here, we determined
      whether corticosteroids can modulate transmitter release directly in the frontal
      cortex and, in doing so, whether they affect presynaptic CB1 cannabinoid receptor
      (CB1R) mediated neuromodulation. By Western blotting of purified subcellular
      fractions of the rat frontal cortex, we found glucocorticoid receptors (GcRs) and
      CB1Rs enriched in isolated frontocortical nerve terminals (synaptosomes). CB1Rs
      were predominantly presynaptically located while GcRs showed preference for the
      post-synaptic fraction. Additional confocal microscopy analysis of cortical and
      hippocampal regions revealed vesicular GABA transporter-positive and vesicular
      glutamate transporter 1-positive nerve terminals endowed with CB1R
      immunoreactivity, apposing GcR-positive post-synaptic compartments. In functional
      transmitter release assay, corticosteroids, corticosterone (0.1-10 microM) and
      dexamethasone (0.1-10 microM) did not significantly affect the evoked release of
      [(3)H]GABA and [(14)C]glutamate in superfused synaptosomes, isolated from both
      rats and mice. In contrast, the synthetic cannabinoid, WIN55212-2 (1 microM)
      diminished the release of both [(3)H]GABA and [(14)C]glutamate, evoked with
      various depolarization paradigms. This effect of WIN55212-2 was abolished by the
      CB1R neutral antagonist, O-2050 (1 microM), and was absent in the CB1R KO mice.
      CB2R-selective agonists did not affect the release of either neurotransmitter.
      The lack of robust presynaptic neuromodulation by corticosteroids was unchanged
      upon either CB1R activation or genetic inactivation. Altogether, corticosteroids
      are unlikely to exert direct non-genomic presynaptic neuromodulation in the
      frontal cortex, but they may do so indirectly, via the stimulation of trans
      synaptic endocannabinoid signaling. 

PMID- 26196380
TI  - Identification of Api88 Binding Partners in Escherichia coli Using a
      Photoaffinity-Cross-Link Strategy and Label-Free Quantification.
AB  - Gene-encoded antimicrobial peptides (AMPs) kill bacteria very efficiently by
      either lytic mechanisms or inhibition of specific bacterial targets. Proline-rich
      AMPs (PrAMPs), for example, produced in insects and mammals rely on the second
      mechanism. They bind to the 70 kDa bacterial heat shock protein DnaK and the 60
      kDa chaperonin GroEL and interfere with protein folding, but this does not
      explain their strong bactericidal effects. Thus, we looked for further binding
      partners of apidaecin 1b, originally identified in honey bees, and two rationally
      optimized analogues (Api88 and Api137). Because affinity chromatography using
      Api88 as an immobilized ligand enriched only a few proteins at low levels besides
      DnaK, we synthesized Api88 analogues substituting Tyr7 with p-benzoyl
      phenylalanine (Bpa), which can cross-link the peptide to binding partners after
      UV irradiation. Escherichia coli was incubated with biotinylated Api88 Tyr7Bpa or
      the corresponding all-d-peptide, irradiated, and lysed. The protein extract was
      enriched by streptavidin, separated by SDS-PAGE, digested with trypsin, and
      analyzed by nanoRP-UPLC-ESI-QqTOF-MS/MS. Among the 41 proteins identified, 34
      were detected only in the l-Api88 Tyr7Bpa sample, including five 70S ribosomal
      proteins, DNA-directed RNA polymerase, and pyruvate dehydrogenase, indicating
      that PrAMPs might interfere with protein translation and energy metabolism. 

PMID- 26196381
TI  - Common Variants in TRDN and CALM1 Are Associated with Risk of Sudden Cardiac
      Death in Chronic Heart Failure Patients in Chinese Han Population.
AB  - BACKGROUND: Recent studies suggest that variants in two calcium handling genes
      (RyR2 and CASQ2) associated with sudden cardiac death (SCD) and non-sudden
      cardiac death (NSCD) in subjects with heart failure and coronary artery disease,
      respectively. The purpose of this study was to identify other calcium handling
      genes associated with SCD in the long-term of chronic heart failure (CHF) in
      Chinese Han population. METHODS AND RESULTS: We investigated 20 SNPs representing
      10 genes that regulated calcium handling in 1429 patients with CHF, and the
      genetic association with SCD and all-cause death was analysed. During a median
      follow-up period of 63 months, 538 patients (37.65%) died from CHF, of whom 185
      (34.38%) had SCD and the others were NSCD. SNPs that pass a P value cut-off of
      0.0025 were considered as significant. We found that patients carrying the CC
      genotype of rs3814843 on CALM1 gene had greater risks of SCD (HR 5.542, 95% CI
      2.054-14.948, P = .001) and all cause death (HR 3.484, 95% CI 1.651-7.350, P =
      .001). After adjusting for other risk factors, significant associations remained.
      Moreover, patients carrying G allele of rs361508 on TRDN gene also had increased
      risk of SCD. CONCLUSIONS: Common variants in TRDN and CALM1 are associated with
      increased risk of SCD in patients with CHF. These findings provide further
      evidence for association of variants in calcium handling regulating proteins and
      SCD in chronic heart failure.

PMID- 26196382
TI  - The Association of LINE-1 Hypomethylation with Age and Centromere Positive
      Micronuclei in Human Lymphocytes.
AB  - Global hypomethylation in white blood cell (WBC) DNA has recently been proposed
      as a potential biomarker for determining cancer risk through genomic instability.
      However, the amplitude of the changes associated with age and the impacts of
      environmental factors on DNA methylation are unclear. In this study, we
      investigated the association of genomic hypomethylation with age, cigarette use,
      drinking status and the presence of centromere positive micronuclei (MNC+)-a
      biomarker for age-dependent genomic instability. Genomic hypomethylation of the
      repetitive element LINE-1 was measured in WBC DNA from 32 healthy male volunteers
      using the pyrosequencing assay. We also measured MNC+ with the micronucleus
      centromere assay using a pan-centromeric probe. Possibly due to the small sample
      size and resulting low statistical power, smoking and drinking status had no
      significant effect on LINE-1 hypomethylation or the occurrence of MNC+.
      Consequently, we did not include them in further analyses. In contrast, LINE-1
      hypomethylation and age significantly predicted MNC+; therefore, we examined
      whether LINE-1 hypomethylation plays a role in MNC+ formation by age, since
      genomic hypomethylation is associated with genomic instability. However, LINE-1
      hypomethylation did not significantly mediate the effect of age on MNC+. Our data
      indicate that the repetitive element LINE-1 is demethylated with age and
      increasing MNC+ frequency, but additional studies are needed to fully understand
      the relation between genomic DNA hypomethylation, age and genomic instability. 

PMID- 26196383
TI  - Functional Principal Component Analysis and Randomized Sparse Clustering
      Algorithm for Medical Image Analysis.
AB  - Due to the advancement in sensor technology, the growing large medical image data
      have the ability to visualize the anatomical changes in biological tissues. As a
      consequence, the medical images have the potential to enhance the diagnosis of
      disease, the prediction of clinical outcomes and the characterization of disease
      progression. But in the meantime, the growing data dimensions pose great
      methodological and computational challenges for the representation and selection
      of features in image cluster analysis. To address these challenges, we first
      extend the functional principal component analysis (FPCA) from one dimension to
      two dimensions to fully capture the space variation of image the signals. The
      image signals contain a large number of redundant features which provide no
      additional information for clustering analysis. The widely used methods for
      removing the irrelevant features are sparse clustering algorithms using a lasso
      type penalty to select the features. However, the accuracy of clustering using a
      lasso-type penalty depends on the selection of the penalty parameters and the
      threshold value. In practice, they are difficult to determine. Recently,
      randomized algorithms have received a great deal of attentions in big data
      analysis. This paper presents a randomized algorithm for accurate feature
      selection in image clustering analysis. The proposed method is applied to both
      the liver and kidney cancer histology image data from the TCGA database. The
      results demonstrate that the randomized feature selection method coupled with
      functional principal component analysis substantially outperforms the current
      sparse clustering algorithms in image cluster analysis.

PMID- 26196385
TI  - Heuristics to Evaluate Interactive Systems for Children with Autism Spectrum
      Disorder (ASD).
AB  - In this paper, we adapted and expanded a set of guidelines, also known as
      heuristics, to evaluate the usability of software to now be appropriate for
      software aimed at children with autism spectrum disorder (ASD). We started from
      the heuristics developed by Nielsen in 1990 and developed a modified set of 15
      heuristics. The first 5 heuristics of this set are the same as those of the
      original Nielsen set, the next 5 heuristics are improved versions of Nielsen's,
      whereas the last 5 heuristics are new. We present two evaluation studies of our
      new heuristics. In the first, two groups compared Nielsen's set with the modified
      set of heuristics, with each group evaluating two interactive systems. The
      Nielsen's heuristics were assigned to the control group while the experimental
      group was given the modified set of heuristics, and a statistical analysis was
      conducted to determine the effectiveness of the modified set, the contribution of
      5 new heuristics and the impact of 5 improved heuristics. The results show that
      the modified set is significantly more effective than the original, and we found
      a significant difference between the five improved heuristics and their
      corresponding heuristics in the original set. The five new heuristics are
      effective in problem identification using the modified set. The second study was
      conducted using a system which was developed to ascertain if the modified set was
      effective at identifying usability problems that could be fixed before the
      release of software. The post-study analysis revealed that the majority of the
      usability problems identified by the experts were fixed in the updated version of
      the system.

PMID- 26196384
TI  - Genomic Analysis of the Emergence and Rapid Global Dissemination of the Clonal
      Group 258 Klebsiella pneumoniae Pandemic.
AB  - Multidrug-resistant Klebsiella pneumoniae producing the KPC carbapenemase have
      rapidly spread throughout the world, causing severe healthcare-associated
      infections with limited antimicrobial treatment options. Dissemination of KPC
      producing K. pneumoniae is largely attributed to expansion of a single dominant
      strain, ST258. In this study, we explore phylogenetic relationships and evolution
      within ST258 and its clonal group, CG258, using whole genome sequence analysis of
      167 isolates from 20 countries collected over 17 years. Our results show a common
      ST258 ancestor emerged from its diverse parental clonal group around 1995 and
      likely acquired blaKPC prior to dissemination. Over the past two decades, ST258
      has remained highly clonal despite diversity in accessory elements and divergence
      in the capsule polysaccharide synthesis locus. Apart from the large recombination
      event that gave rise to ST258, few mutations set it apart from its clonal group.
      However, one mutation occurs in a global transcription regulator.
      Characterization of outer membrane protein sequences revealed a profile in ST258
      that includes a truncated OmpK35 and modified OmpK37. Our work illuminates
      potential genomic contributors to the pathogenic success of ST258, helps us
      better understand the global dissemination of this strain, and identifies genetic
      markers unique to ST258.

PMID- 26196386
TI  - Mapping of Schistosomiasis and Soil-Transmitted Helminths in Namibia: The First
      Large-Scale Protocol to Formally Include Rapid Diagnostic Tests.
AB  - BACKGROUND: Namibia is now ready to begin mass drug administration of
      praziquantel and albendazole against schistosomiasis and soil-transmitted
      helminths, respectively. Although historical data identifies areas of
      transmission of these neglected tropical diseases (NTDs), there is a need to
      update epidemiological data. For this reason, Namibia adopted a new protocol for
      mapping of schistosomiasis and geohelminths, formally integrating rapid
      diagnostic tests (RDTs) for infections and morbidity. In this article, we explain
      the protocol in detail, and introduce the concept of 'mapping resolution', as
      well as present results and treatment recommendations for northern Namibia.
      METHODS/FINDINGS/INTERPRETATION: This new protocol allowed a large sample to be
      surveyed (N = 17,896 children from 299 schools) at relatively low cost (7 USD per
      person mapped) and very quickly (28 working days). All children were analysed by
      RDTs, but only a sub-sample was also diagnosed by light microscopy. Overall
      prevalence of schistosomiasis in the surveyed areas was 9.0%, highly associated
      with poorer access to potable water (OR = 1.5, P<0.001) and defective (OR = 1.2,
      P<0.001) or absent sanitation infrastructure (OR = 2.0, P<0.001). Overall
      prevalence of geohelminths, more particularly hookworm infection, was 12.2%,
      highly associated with presence of faecal occult blood (OR = 1.9, P<0.001).
      Prevalence maps were produced and hot spots identified to better guide the
      national programme in drug administration, as well as targeted improvements in
      water, sanitation and hygiene. The RDTs employed (circulating cathodic antigen
      and microhaematuria for Schistosoma mansoni and S. haematobium, respectively)
      performed well, with sensitivities above 80% and specificities above 95%.
      CONCLUSION/SIGNIFICANCE: This protocol is cost-effective and sensitive to budget
      limitations and the potential economic and logistical strains placed on the
      national Ministries of Health. Here we present a high resolution map of disease
      prevalence levels, and treatment regimens are recommended.

PMID- 26196388
TI  - Correction: Remembering the Object You Fear: Brain Potentials during Recognition
      of Spiders in Spider-Fearful Individuals.

PMID- 26196387
TI  - Genome Wide Re-Annotation of Caldicellulosiruptor saccharolyticus with New
      Insights into Genes Involved in Biomass Degradation and Hydrogen Production.
AB  - Caldicellulosiruptor saccharolyticus has proven itself to be an excellent
      candidate for biological hydrogen (H2) production, but still it has major
      drawbacks like sensitivity to high osmotic pressure and low volumetric H2
      productivity, which should be considered before it can be used industrially. A
      whole genome re-annotation work has been carried out as an attempt to update the
      incomplete genome information that causes gap in the knowledge especially in the
      area of metabolic engineering, to improve the H2 producing capabilities of C.
      saccharolyticus. Whole genome re-annotation was performed through manual means
      for 2,682 Coding Sequences (CDSs). Bioinformatics tools based on sequence
      similarity, motif search, phylogenetic analysis and fold recognition were
      employed for re-annotation. Our methodology could successfully add functions for
      409 hypothetical proteins (HPs), 46 proteins previously annotated as putative and
      assigned more accurate functions for the known protein sequences. Homology based
      gene annotation has been used as a standard method for assigning function to
      novel proteins, but over the past few years many non-homology based methods such
      as genomic context approaches for protein function prediction have been
      developed. Using non-homology based functional prediction methods, we were able
      to assign cellular processes or physical complexes for 249 hypothetical
      sequences. Our re-annotation pipeline highlights the addition of 231 new CDSs
      generated from MicroScope Platform, to the original genome with functional
      prediction for 49 of them. The re-annotation of HPs and new CDSs is stored in the
      relational database that is available on the MicroScope web-based platform. In
      parallel, a comparative genome analyses were performed among the members of genus
      Caldicellulosiruptor to understand the function and evolutionary processes.
      Further, with results from integrated re-annotation studies (homology and genomic
      context approach), we strongly suggest that Csac_0437 and Csac_0424 encode for
      glycoside hydrolases (GH) and are proposed to be involved in the decomposition of
      recalcitrant plant polysaccharides. Similarly, HPs: Csac_0732, Csac_1862,
      Csac_1294 and Csac_0668 are suggested to play a significant role in biohydrogen
      production. Function prediction of these HPs by using our integrated approach
      will considerably enhance the interpretation of large-scale experiments targeting
      this industrially important organism.

PMID- 26196389
TI  - Molecular and Morphological Species Boundaries in the Gorgonian Octocoral Genus
      Pterogorgia (Octocorallia: Gorgoniidae).
AB  - Most gorgonian octocoral species are described using diagnostic characteristics
      of their sclerites (microscopic skeletal components). Species in the genus
      Pterogorgia, however, are separated primarily by differences in their calyx and
      branch morphology. Specimens of a morphologically unusual Pterogorgia collected
      from Saba Bank in the NE Caribbean Sea were found with calyx morphology similar
      to P. citrina and branch morphology similar to P. guadalupensis. In order to test
      morphological species boundaries, and the validity of calyx and branch morphology
      as systematic characters, a phylogenetic analysis was undertaken utilizing
      partial gene fragments of three mitochondrial (mtMutS, cytochrome b, and igr4;
      726bp total) and two nuclear (ITS2, 166bp; and SRP54 intron, 143bp) loci. The
      datasets for nuclear and mitochondrial loci contained few phylogenetically
      informative sites, and tree topologies did not resolve any of the morphological
      species as monophyletic groups. Instead, the mitochondrial loci and SRP54 each
      recovered two clades but were slightly incongruent, with a few individuals of P.
      guadalupensis represented in both clades with SRP54. A concatenated dataset of
      these loci grouped all P. anceps and P. guadalupensis in a clade, and P. citrina
      and the Pterogorgia sp. from Saba Bank in a sister clade, but with minimal
      variation/resolution within each clade. However, in common with other octocoral
      taxa, the limited genetic variation may not have been able to resolve whether
      branch variation represents intraspecific variation or separate species.
      Therefore, these results suggest that there are at least two phylogenetic
      lineages of Pterogorgia at the species level, and the atypical Pterogorgia sp.
      may represent an unusual morphotype of P. citrina, possibly endemic to Saba Bank.
      Branch morphology does not appear to be a reliable morphological character to
      differentiate Pterogorgia species (e.g., branches "flat" or "3-4 edges" in P.
      guadalupensis and P. anceps, respectively), and a re-evaluation of species-level
      characters (e.g., sclerites) is needed.

PMID- 26196390
TI  - Inhibition of ANO1/TMEM16A Chloride Channel by Idebenone and Its Cytotoxicity to
      Cancer Cell Lines.
AB  - The expression levels of anoctamin 1 (ANO1, TMEM16A), a calcium-activated
      chloride channel (CaCC), are significantly increased in several tumors, and
      inhibition of ANO1 is known to reduce cell proliferation and migration. Here, we
      performed cell-based screening of a collection of natural products and drug-like
      compounds to identify inhibitors of ANO1. As a result of the screening,
      idebenone, miconazole and plumbagin were identified as novel ANO1 inhibitors.
      Electrophysiological studies showed that idebenone, a synthetic analog of
      coenzyme Q10, completely blocked ANO1 activity in FRT cells expressing ANO1
      without any effect on intracellular calcium signaling and CFTR, a cAMP-regulated
      chloride channel. The CaCC activities in PC-3 and CFPAC-1 cells expressing
      abundant endogenous ANO1 were strongly blocked by idebenone. Idebenone inhibited
      cell proliferation and induced apoptosis in PC-3 and CFPAC-1 cells, but not in
      A549 cells, which do not express ANO1. These data suggest that idebenone, a novel
      ANO1 inhibitor, has potential for use in cancer therapy.

PMID- 26196391
TI  - Dietary Caprylic Acid (C8:0) Does Not Increase Plasma Acylated Ghrelin but
      Decreases Plasma Unacylated Ghrelin in the Rat.
AB  - Focusing on the caprylic acid (C8:0), this study aimed at investigating the
      discrepancy between the formerly described beneficial effects of dietary medium
      chain fatty acids on body weight loss and the C8:0 newly reported effect on food
      intake via ghrelin octanoylation. During 6 weeks, Sprague-Dawley male rats were
      fed with three dietary C8:0 levels (0, 8 and 21% of fatty acids) in three
      experimental conditions (moderate fat, caloric restriction and high fat). A
      specific dose-response enrichment of the stomach tissue C8:0 was observed as a
      function of dietary C8:0, supporting the hypothesis of an early preduodenal
      hydrolysis of medium chain triglycerides and a direct absorption at the gastric
      level. However, the octanoylated ghrelin concentration in the plasma was
      unchanged in spite of the increased C8:0 availability. A reproducible decrease in
      the plasma concentration of unacylated ghrelin was observed, which was consistent
      with a decrease in the stomach preproghrelin mRNA and stomach ghrelin expression.
      The concomitant decrease of the plasma unacylated ghrelin and the stability of
      its acylated form resulted in a significant increase in the acylated/total
      ghrelin ratio which had no effect on body weight gain or total dietary
      consumption. This enhanced ratio measured in rats consuming C8:0 was however
      suspected to increase (i) growth hormone (GH) secretion as an increase in the GH
      dependent mRNA expression of the insulin like growth Factor 1 (IGF-1) was
      measured (ii) adipocyte diameters in subcutaneous adipose tissue without an
      increase in the fat pad mass. Altogether, these results show that daily feeding
      with diets containing C8:0 increased the C8:0 level in the stomach more than all
      the other tissues, affecting the acylated/total ghrelin plasma ratio by
      decreasing the concentration of circulating unacylated ghrelin. However, these
      modifications were not associated with increased body weight or food consumption.

PMID- 26196392
TI  - Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the
      Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo.
AB  - Esophageal squamous cell carcinomas (ESCC) have become a severe threat to health
      and the current treatments for ESCC are frequently not effective. Recent
      epidemiological studies suggest that the anti-hyperglycemic agent metformin may
      reduce the risk of developing cancer, including ESCC, among diabetic patients.
      However, the antitumor effects of metformin on ESCC and the mechanisms underlying
      its cell cycle regulation remain elusive. The findings reported herein show that
      the anti-proliferative action of metformin on ESCC cell lines is partially
      mediated by AMPK. Moreover, we observed that metformin induced G0/G1 phase arrest
      accompanied by the up-regulation of p21CIP1 and p27KIP1. In vivo experiments
      further showed that metformin inhibited tumor growth in a ESCC xenograft model.
      Most importantly, the up-regulation of AMPK, p53, p21CIP1, p27KIP1 and the down
      regulation of cyclinD1 are involved in the anti-tumor action of metformin in
      vivo. In conclusion, metformin inhibits the growth of ESCC cells both in cell
      cultures and in an animal model. AMPK, p53, p21CIP1, p27KIP1 and cyclinD1 are
      involved in the inhibition of tumor growth that is induced by metformin and cell
      cycle arrest in ESCC. These findings indicate that metformin has the potential
      for use in the treatment of ESCC.

PMID- 26196393
TI  - The Genetic Relationship between Leishmania aethiopica and Leishmania tropica
      Revealed by Comparing Microsatellite Profiles.
AB  - BACKGROUND: Leishmania (Leishmania) aethiopica and L. (L.) tropica cause
      cutaneous leishmaniases and appear to be related. L. aethiopica is geographically
      restricted to Ethiopia and Kenya; L. tropica is widely dispersed from the Eastern
      Mediterranean, through the Middle East into eastern India and in north, east and
      south Africa. Their phylogenetic inter-relationship is only partially revealed.
      Some studies indicate a close relationship. Here, eight strains of L. aethiopica
      were characterized genetically and compared with 156 strains of L. tropica from
      most of the latter species' geographical range to discern the closeness.
      METHODOLOGY/PRINCIPAL FINDINGS: Twelve unlinked microsatellite markers previously
      used to genotype strains of L. tropica were successfully applied to the eight
      strains of L. aethiopica and their microsatellite profiles were compared to those
      of 156 strains of L. tropica from various geographical locations that were
      isolated from human cases of cutaneous and visceral leishmaniasis, hyraxes and
      sand fly vectors. All the microsatellite profiles were subjected to various
      analytical algorithms: Bayesian statistics, distance-based and factorial
      correspondence analysis, revealing: (i) the species L. aethiopica, though
      geographically restricted, is genetically very heterogeneous; (ii) the strains of
      L. aethiopica formed a distinct genetic cluster; and (iii) strains of L.
      aethiopica are closely related to strains of L. tropica and more so to the
      African ones, although, by factorial correspondence analysis, clearly separate
      from them. CONCLUSIONS/SIGNIFICANCE: The successful application of the 12
      microsatellite markers, originally considered species-specific for the species L.
      tropica, to strains of L. aethiopica confirmed the close relationship between
      these two species. The Bayesian and distance-based methods clustered the strains
      of L. aethiopica among African strains of L. tropica, while the factorial
      correspondence analysis indicated a clear separation between the two species.
      There was no correlation between microsatellite profiles of the eight strains of
      L. aethiopica and the type of leishmaniasis, localized (LCL) versus diffuse
      cutaneous leishmaniasis (DCL), displayed by the human cases.

PMID- 26196394
TI  - Illicit Heroin and Methamphetamine Use among Methadone Maintenance Treatment
      Patients in Dehong Prefecture of Yunnan Province, China.
AB  - OBJECTIVE: Methadone maintenance treatment (MMT) was introduced to China in 2004
      to reduce the harm of injecting drug users (IDUs). However, little is known about
      continued drug use, especially methamphetamine (MAMP), among MMT patients.
      METHODS: A survey was conducted among patients attending five major MMT clinics
      in Dehong Prefecture in 2014 to investigate the heroin and MAMP use and their
      associated risk factors. Participants were administered with face-to-face
      interviews, and urine tests for morphine and MAMP. RESULTS: A total of 2,121 were
      eligible and participated in the study. Among them, 220 (10.4%) were only
      positive for morphine, 12.9% were only positive for MAMP, and 196 (9.2%) were
      positive for both morphine and MAMP. Compared with neither use of heroin nor MAMP
      during MMT, heroin use (not using MAMP) was associated with ethnicity, shorter
      duration of MMT, lower dose of methadone, and having had no more than two sex
      partners in the past year; MAMP use (not using heroin) was associated with
      ethnicity, longer duration of MMT, higher dose of methadone and being aged <30
      years (vs. >=50 years); use of both heroin and MAMP was associated with being Dai
      minority (vs. Han), a marital status of divorced or widowed, having used drugs
      for >=10 years and shorter duration of MMT. CONCLUSION: These findings indicate
      the complexity in the treatment of heroin users and underscore the importance in
      prescribing appropriate methadone dosages in order to reduce both heroin and MAMP
      use.

PMID- 26196395
TI  - Stress Responses of Small Heat Shock Protein Genes in Lepidoptera Point to
      Limited Conservation of Function across Phylogeny.
AB  - The small heat shock protein (sHsp) family is thought to play an important role
      in protein refolding and signal transduction, and thereby protect organisms from
      stress. However little is known about sHsp function and conservation across
      phylogenies. In the current study, we provide a comprehensive assessment of small
      Hsp genes and their stress responses in the oriental fruit moth (OFM), Grapholita
      molesta. Fourteen small heat shock proteins of OFM clustered with related Hsps in
      other Lepidoptera despite a high level of variability among them, and in contrast
      to the highly conserved Hsp11.1. The only known lepidopteran sHsp ortholog
      (Hsp21.3) was consistently unaffected under thermal stress in Lepidoptera where
      it has been characterized. However the phylogenetic position of the sHsps within
      the Lepidoptera was not associated with conservation of induction patterns under
      thermal extremes or diapause. These findings suggest that the sHsps have evolved
      rapidly to develop new functions within the Lepidoptera.

PMID- 26196396
TI  - Structural Evolution of Tcn (n = 4-20) Clusters from First-Principles Global
      Minimization.
AB  - We explore the structural evolution of Tcn (n = 4-20) clusters using a first
      principles global minimization technique, namely, basin-hopping from density
      functional theory geometry optimization (BH-DFT). Significantly more stable
      structures have been found in comparison with previous models, indicating the
      power of DFT-based basin hopping in finding new structures for clusters. The
      growth sequence and pattern for n from 4 to 20 are analyzed from the perspective
      of geometric shell formation. The binding energy per atom, relative stability,
      and magnetic moments are examined as a function of the cluster size. Several
      magic sizes of higher stability and symmetry are discovered. In particular, we
      find that Tc19 prefers an Oh symmetry structure, resembling a piece of a face
      centered-cubic metal, and its electrostatic potential map shows interesting
      features that indicate special reactivity of the corner atoms. 

PMID- 26196397
TI  - Modeling Photo-Bleaching Kinetics to Create High Resolution Maps of Rod Rhodopsin
      in the Human Retina.
AB  - We introduce and describe a novel non-invasive in-vivo method for mapping local
      rod rhodopsin distribution in the human retina over a 30-degree field. Our
      approach is based on analyzing the brightening of detected lipofuscin
      autofluorescence within small pixel clusters in registered imaging sequences
      taken with a commercial 488nm confocal scanning laser ophthalmoscope (cSLO) over
      a 1 minute period. We modeled the kinetics of rhodopsin bleaching by applying
      variational optimization techniques from applied mathematics. The physical model
      and the numerical analysis with its implementation are outlined in detail. This
      new technique enables the creation of spatial maps of the retinal rhodopsin and
      retinal pigment epithelium (RPE) bisretinoid distribution with an ~ 50MUm
      resolution. 

PMID- 26196398
TI  - Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study.
AB  - In a meta-analysis with multiple end points of interests that are correlated
      between or within studies, multivariate approach to meta-analysis has a potential
      to produce more precise estimates of effects by exploiting the correlation
      structure between end points. However, under random-effects assumption the
      multivariate estimation is more complex (as it involves estimation of more
      parameters simultaneously) than univariate estimation, and sometimes can produce
      unrealistic parameter estimates. Usefulness of multivariate approach to meta
      analysis of the effects of a genetic variant on two or more correlated traits is
      not well understood in the area of genetic association studies. In such studies,
      genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium
      within studies, and also their effects on complex traits are generally very small
      to modest and could be heterogeneous across studies for genuine reasons. We
      carried out extensive simulation to explore the comparative performance of
      multivariate approach with most commonly used univariate inverse-variance
      weighted approach under random-effects assumption in various realistic meta
      analytic scenarios of genetic association studies of correlated end points. We
      evaluated the performance with respect to relative mean bias percentage, and root
      mean square error (RMSE) of the estimate and coverage probability of
      corresponding 95% confidence interval of the effect for each end point. Our
      simulation results suggest that multivariate approach performs similarly or
      better than univariate method when correlations between end points within or
      between studies are at least moderate and between-study variation is similar or
      larger than average within-study variation for meta-analyses of 10 or more
      genetic studies. Multivariate approach produces estimates with smaller bias and
      RMSE especially for the end point that has randomly or informatively missing
      summary data in some individual studies, when the missing data in the endpoint
      are imputed with null effects and quite large variance.

PMID- 26196399
TI  - Anti-inflammatory function of ginsenoside Rg1 on alcoholic hepatitis through
      glucocorticoid receptor related nuclear factor-kappa B pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is the dried root of Panax ginseng C.A.
      Mayer. Since ancient times, ginseng has been used as one kind of treatment drug
      or tonic in China and even other eastern countries like Korea and Japan.
      Pharmacological active chemical ingredients and its extract of ginseng are a
      mixture of triterpenoid saponins, collectively called ginsenosides. Among them,
      ginsenoside Rg1 is the most pharmacological active one. AIM OF THE STUDY: Based
      on prior experimental results and the understanding of alcoholic hepatitis, the
      major aim of this study is to investigate whether Rg1 is beneficial in a rodent
      model mimic alcoholic hepatic injury associated with binge drinking and explore
      the underlying possible mechanisms. MATERIALS AND METHODS: C57BL/6 mice were
      given oral consumption of 6g/kg alcohol 1h after treated with Rg1 (10, 20 and
      40mg/kg) or dexamethasone (1mg/kg) for 9 consecutive days. Biochemical analyses
      were performed and liver fragments were processed for microscopy,
      immunohistochemistry and western blot analysis. RESULTS: According to our data,
      Rg1 treatment significantly reversed the high mortality rate induced by alcohol
      consumption and also alleviated liver impairment as evidenced by the decrease of
      serum parameters. Meanwhile, histological and ultrastructural analysis of
      alcoholic groups showed hepatocellular impairment but restored in Rg1-treated
      groups. Overproductive inflammatory cytokines were also suppressed by Rg1 in
      alcohol-intoxicated mouse livers. In addition, changes of GR related NF-kappaB
      pathway, including phospho-IkappaB-alpha, were also modulated to normal levels.
      CONCLUSION: This study demonstrates that Rg1 might promote GR mediating the
      repression of NF-kappaB and inhibit the inflammatory reactions in alcoholic
      hepatitis.

PMID- 26196400
TI  - Effect of total flavonoids from the seeds of Astragali complanati on natural
      killer cell function.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Astragalus complanatus R.Br. (AC), a
      traditional Chinese medicine, have been extensively used for clinical treatment
      of liver and kidney complaints and tumors for more than a thousand years. It was
      believed that AC is warm and sweet in the most authoritative medical book of
      Ancient China "Compendium of Materia Medica". Our previous studies showed that
      the flavonoid component from the seeds of Astragalus complanatus (FAC) is mainly
      an active constituent and has the hepatoprotective effect, anti-liver fibrosis,
      and anti-tumor and immune enhancement. AIM: The aim of this study was to
      investigate in vitro the regulation effect of FAC on NK cells function and
      possible mechanism of action. METHODS: The effect of FAC on the proliferation
      ability of NK-92 cells and the cytolysis of NK-92 cells to K562 and SMMC-7721
      were measured by MTT assay and lactase dehydrogenase (LDH)-releasing assay,
      respectively. The phenotypical characterization (CD3, CD16 and CD56) and
      activation markers (CD25, CD69 and CD95) of NK-92 cell were detected by flow
      cytometry analysis. IFN-gamma production of NK-92 cells stimulating by K562 cells
      was quantitated using ELISA. To explore the mechanism of action, mRNA and protein
      expressions of activating receptors (NKp30, NKp44, NKp46 and NKG2D) in NK-92
      cells were detected by quantitative real-time PCR and flow cytometry analysis.
      RESULTS: Our results demonstrated that FAC significantly promoted the
      proliferation and the cytotoxicity of NK-92 cells in a dose-dependent manner by
      enhancing IFN-gamma and increasing the expression of the activation markers CD25
      and CD69. In addition, FAC had not changed the NK-92 cells phenotypical
      characterization, but markedly enhanced the expression intensity of CD56.
      Furthermore, FAC significantly enhanced mRNA and protein expressions lever of
      NKp44 and NKG2D in NK-92 cells. CONCLUSION: These results suggest that FAC
      upregulate the expressions of NKG2D, NKp44, which in turn influence NK-92 cells
      activation. FAC may serve as an immunostimulatory of NK cells for tumor
      treatment.

PMID- 26196402
TI  - Aqueous extract of Agrostemma githago seed inhibits caspase-3 and induces cell
      cycle arrest at G1 phase in AGS cell line.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A weed plant belonging to the Caryophyllaceae
      family, Agrostemma githago is used in folk medicine to treat cancers and warts.
      AIM OF THE STUDY: The aim of this study was to evaluate the cytotoxic effect of
      the aqueous extract of A. githago seed on gastric cancer cell line (AGS) and to
      investigate the mechanism of apoptosis induction in these cells. MATERIALS AND
      METHODS: Seeds of A. githago were collected from the suburban area of Ardabil
      Province, northwest Iran. After preparing the aqueous extract, dry matter was
      harvested with the lyophilizing technique. The 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay was used to assess the cytotoxicity.
      Apoptotic cells were detected by staining with ethidium bromide/acridine orange
      (EB/AO). Diamidino-2-phenylindole (DAPI) staining was used for cell-cycle
      analysis with a flow cytometer. The annexin V binding level, caspase-3 activity,
      and B-cell lymphoma-2 (Bcl-2) level were also measured to confirm apoptotic cell
      death. RESULTS: After the aqueous extract of A. githago seed was incubated for
      24, 48, and 72 h, inhibited cell growth was observed with IC50 values of 13.51 +/
      0.7, 4.37 +/- 1.01, and 2.42 +/- 0.8 ug/ml, respectively. The EB/AO staining
      method demonstrated that the extract exerts its cytotoxic effect mainly via
      apoptosis, in accordance with the annexin V, blc-2, and caspase-3 results. The
      extract showed a concentration-dependent increase in annexin V binding to
      externally exposed phosphatidylserine as well as caspase-3 activity. The bcl-2
      protein level showed a proportionate decrease with the increase in extract
      concentration. The cell-cycle analysis revealed that the extract can arrest cells
      at the G1 checkpoint. CONCLUSION: The findings of this study revealed the
      cytotoxic effect of the aqueous extract of A. githago seed on gastric cancer
      cells (AGS) mainly via apoptosis and the cell-cycle arrest at the G1 checkpoint.
      Therefore, the extract can be potentially used in gastric cancer therapy in
      vitro.

PMID- 26196401
TI  - Topical anti-inflammatory activity of semisolid containing standardized Aleurites
      moluccana L. Willd (Euphorbiaceae) leaves extract.
AB  - ETHNOPHARMMACOLOGICAL RELEVANCE: Aleurites moluccana is a medicinal plant
      popularly used to treat pain, fever, asthma, hepatitis, gastric ulcer and
      inflammatory process in general. Recently, pre-clinical studies have demonstrated
      that the dry extract obtained from A. moluccana leaves was effective as
      analgesic, anti-inflammatory and wound healing. AIM: The present study has aimed
      to evaluate the mechanisms involved in the topical anti-inflammatory effects of
      the semisolid containing 10mg/g of A. moluccana dried extract. MATERIAL AND
      METHODS: Ear edema induced by croton oil (2.5%) in mice was used throughout the
      study. The level of cytokines tumour necrosis factor (TNF) and interleukine-1beta
      (IL-1beta) and chemokine keratinocyte chemoattractant (CXCL1/KC), and neutrophil
      migration were quantified. The histological analysis has also been performed.
      RESULTS: The topical treatment with the semisolid was able to significantly
      inhibite the ear edema (35.77+/-7.35%). This effect was accompanied by the
      reduction of leukocyte migration, as well as TNF (53.75+/-12.96%), IL-1beta
      (38.36+/-5.92%), and CXCL1/KC (62.29+/-11.65%) decreased levels. CONCLUSIONS:
      This study demonstrated for the first time the mechanisms involved in the topical
      anti-inflammatory effect presented by the semisolid containing A. moluccana dried
      extract pointing as the main mechanism is the reduction in the leukocyte
      migration and consequently resulting in diminished levels of cytokins and
      chemokines, indicating this herbal product as a promissor anti-inflammatory
      phytomedicine to treat skin inflammatory diseases.

PMID- 26196403
TI  - The neuritogenic and synaptogenic effects of the ethanolic extract of radix
      Puerariae in cultured rat hippocampal neurons.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Radix Puerariae, the root of Pueraria montana
      var. lobata (Willd.) Sanjappa & Pradeep, is used in Korean traditional medicine
      to treat neuronal disorders including Parkinson's disease, and its active
      constituent, puerarin has been reported to have a neuroprotective effect in
      experimental models of Parkinson's and Alzheimer's disease. AIMS OF THE STUDY: To
      investigate the neurotrophic effects of these ethnomedicines on the development
      of central nervous system neurons and the molecular bases of these activities.
      MATERIALS AND METHODS: Rat embryonic (E19) brain neurons were cultured in the
      absence or presence of the ethanolic extract of Radix Puerariae (RPE) or
      puerarin. At predetermined times, cells were fixed and immunostained to visualize
      neuronal morphologies, or lysed for protein harvesting. Morphometric analyses of
      neurite outgrowths and synaptogenesis were performed using Image J software. RPE
      or puerarin-mediated changes in the protein profiles of cultured neurons were
      assessed by MALDI-TOF-MS/PMF and measuring immunofluorescent intensities.
      RESULTS: RPE and puerarin alone promoted maximum neurite outgrowths at
      concentrations of 1ug/ml and 5uM, respectively. At these optimal concentrations,
      RPE and puerarin provided neurotrophic support by promoting axo-dendritic arbors
      and synapse formation in cultured neurons. Proteomic study revealed that RPE and
      puerarin both up-regulated a number of proteins, including dynein light chain 2
      (DLC2) and elongation factor 2 (EF2), which are associated with neuritogenesis
      and synaptic potentiation, respectively. Immunofluorescence intensity
      measurements confirmed the expressions of the DLC2 and Dync1h1 subunits of dynein
      in RPE or puerarin treated hippocampal neurons were up-regulated when RPE or
      puerarin induced changes in neuronal cytoarchitecture. CONCLUSIONS: Our study
      demonstrates that RPE and puerarin should be considered potentially valuable
      preventative therapeutics for brain disorders due to their abilities to promote
      the neuronal cytoarchitecture and the synaptic functionality, which are possibly
      associated with dynein-dependent regulation of cytoskeletal structures and up
      regulation of translation machinery.

PMID- 26196404
TI  - Anammox-based technologies for nitrogen removal: Advances in process start-up and
      remaining issues.
AB  - Nitrogen removal from wastewater via anaerobic ammonium oxidation (anammox)-based
      process has been recognized as efficient, cost-effective and low energy
      alternative to the conventional nitrification and denitrification processes. To
      date, more than one hundred full-scale anammox plants have been installed and
      operated for treatment of NH4(+)-rich wastewater streams around the world, and
      the number is increasing rapidly. Since the discovery of anammox process,
      extensive researches have been done to develop various anammox-based
      technologies. However, there are still some challenges in practical application
      of anammox-based treatment process at full-scale, e.g., longer start-up period,
      limited application to mainstream municipal wastewater and poor effluent water
      quality. This paper aimed to summarize recent status of application of anammox
      process and researches on technological development for solving these remaining
      problems. In addition, an integrated system of anammox-based process and
      microbial fuel cell is proposed for sustainable and energy-positive wastewater
      treatment. 

PMID- 26196405
TI  - Catalyzing the oxidation of sulfamethoxazole by permanganate using molecular
      sieves supported ruthenium nanoparticles.
AB  - This study developed a heterogeneous catalytic permanganate oxidation system with
      three molecular sieves, i.e., nanosized ZSM-5 (ZSM-5A), microsized ZSM-5 (ZSM-5B)
      and MCM-41, supported ruthenium nanoparticles as catalyst, denoted as Ru/ZSM-5A,
      Ru/ZSM-5B and Ru/MCM-41, respectively. The presence of 0.5gL(-1) Ru/ZSM-5A,
      Ru/ZSM-5B and Ru/MCM-41 increased the oxidation rate of sulfamethoxazole (SMX) by
      permanganate at pH 7.0 by 27-1144 times. The catalytic performance of Ru
      catalysts toward SMX oxidation by permanganate was strongly dependent on Ru
      loading on the catalysts. The X-ray absorption near edge structure (XANES) and
      extended X-ray absorption fine structure (EXAFS) analyses confirmed that Ru
      catalyst acted as an electron shuttle in catalytic permanganate oxidation
      process. Ru(III) deposited on the surface of catalysts was oxidized by
      permanganate to its higher oxidation state Ru(VII), which could work as a co
      oxidant with permanganate to decompose SMX and was then reduced to its initial
      tri-valence. During the successive runs, Ru/ZSM-5A could not maintain its
      catalytic activity due to the deposition of MnO2, which was the reductive product
      of permanganate, onto the surface of Ru/ZSM-5A. Thus, the regeneration of
      partially deactivated Ru catalysts by reductant NH2OH?HCl or ascorbic acid was
      proposed. Ru/ZSM-5A regenerated by NH2OH?HCl displayed comparable catalytic
      ability to its virgin counterpart, while ascorbic acid could not completely
      remove the deposited MnO2. A trace amount of leaching of Ru into the reaction
      solution was also observed, which would be ameliorated by improving the
      preparation conditions in the future study. 

PMID- 26196406
TI  - Column bioleaching copper and its kinetics of waste printed circuit boards
      (WPCBs) by Acidithiobacillus ferrooxidans.
AB  - Application of bioleaching process for metal recovery from electronic waste has
      received an increasing attention in recent years. In this work, a column
      bioleaching of copper from waste printed circuit boards (WPCBs) by
      Acidithiobacillus ferrooxidans has been investigated. After column bioleaching
      for 28d, the copper recovery reached at 94.8% from the starting materials
      contained 24.8% copper. Additionally, the concentration of Fe(3+) concentration
      varied significantly during bioleaching, which inevitably will influence the Cu
      oxidation, thus bioleaching process. Thus the variation in Fe(3+) concentration
      should be taken into consideration in the conventional kinetic models of
      bioleaching process. Experimental results show that the rate of copper
      dissolution is controlled by external diffusion rather than internal one because
      of the iron hydrolysis and formation of jarosite precipitates at the surface of
      the material. The kinetics of column bioleaching WPCBs remains unchanged because
      the size and morphology of precipitates are unaffected by maintaining the pH of
      solution at 2.25 level. In bioleaching process, the formation of jarosite
      precipitate can be prevented by adding dilute sulfuric acid and maintaining an
      acidic condition of the leaching medium. In such way, the Fe(2)(+)-Fe(3+) cycle
      process can kept going and create a favorable condition for Cu bioleaching. Our
      experimental results show that column Cu bioleaching from WPCBs by A.
      ferrooxidans is promising. 

PMID- 26196407
TI  - Choice of Antihypertensive Combination Therapy Based on Daily Salt Intake.
AB  - BACKGROUND: It is unclear whether thiazide diuretics (TZs) or calcium channel
      blockers (CCBs) are more effective as add-on therapy to angiotensin receptor
      blockers (ARBs) in controlling hypertension. Because TZs are a rational choice in
      salt-sensitive hypertension, patients with high salt intake might preferentially
      benefit from ARB/TZ over ARB/CCB combination therapy. METHODS: Hypertensive
      patients who failed to reach blood pressure goals despite treatment with ARBs
      alone were randomly assigned to receive either ARB/TZ or ARB/CCB combination
      therapy. Estimated daily sodium intake was calculated from spot urine values of
      sodium and creatinine. RESULTS: Blood pressure was measured at baseline, and at
      4, 8 and 12 weeks after starting combination therapy. For all study patients (n =
      87), diastolic blood pressure reduction was greater in patients receiving ARB/CCB
      treatment. However, in the 37 patients with a baseline estimated daily salt
      intake greater than 10 g and baseline systolic blood pressure (SBP) ranging from
      150 to 200 mm Hg, SBP was lower (P < 0.05) and SBP reduction was greater (P <
      0.05) 4 weeks after starting combination therapy in those receiving ARB/TZ
      treatment. In the 31 patients whose estimated daily salt intake increased at 12
      weeks compared with baseline, SBP at 12 weeks was lower in those receiving ARB/TZ
      treatment (P < 0.05). CONCLUSIONS: Estimated daily salt intake is a useful tool
      for guiding antihypertensive therapy and should be measured repeatedly during the
      therapeutic course.

PMID- 26196408
TI  - Atomic-Scale Dynamics of Surface-Catalyzed Hydrogenation/Dehydrogenation: NH on
      Pt(111).
AB  - Low-temperature scanning tunneling microscopy (LT-STM) was used to move hydrogen
      atoms and dissociate NH molecules on a Pt(111) surface covered with an ordered
      array of nitrogen atoms in a (2 * 2) structure. The N-covered Pt(111) surface was
      prepared by ammonia oxydehydrogenation, which was achieved by annealing an
      ammonia-oxygen overlayer to 400 K. Exposing the N-covered surface to H2(g) forms
      H atoms and NH molecules. The NH molecules occupy face-centered cubic hollow
      sites, while the H atoms occupy atop sites. The STM tip was used to dissociate NH
      and to induce hopping of H atoms. Action spectra consisting of the reaction yield
      versus applied bias voltage were recorded for both processes, which revealed that
      they are vibrationally mediated. The threshold voltages for NH dissociation and H
      hopping were found to be 430 and 272 meV, corresponding to the excitation energy
      of the N-H stretching and the Pt-H stretching modes, respectively. Substituting H
      with D results in an isotopic shift of -110 and -84 meV for the threshold
      voltages for ND dissociation and D hopping, respectively. This further supports
      the conclusion that these processes are vibrationally mediated. 

PMID- 26196410
TI  - Leverage Between the Buffering Effect and the Bystander Effect in Social
      Networking.
AB  - This study examined encouraged and inhibited social feedback behaviors based on
      the theories of the buffering effect and the bystander effect. A system program
      was used to collect personal data and social feedback from a Facebook data set to
      test the research model. The results revealed that the buffering effect induced a
      positive relationship between social network size and feedback gained from
      friends when people's social network size was under a certain cognitive
      constraint. For people with a social network size that exceeds this cognitive
      constraint, the bystander effect may occur, in which having more friends may
      inhibit social feedback. In this study, two social psychological theories were
      applied to explain social feedback behavior on Facebook, and it was determined
      that social network size and social feedback exhibited no consistent linear
      relationship. 

PMID- 26196411
TI  - Motivations for Reducing Other HIV Risk-Reduction Practices if Taking Pre
      Exposure Prophylaxis: Findings from a Qualitative Study Among Women in Kenya and
      South Africa.
AB  - Findings from a survey conducted among women at high risk for HIV in Bondo,
      Kenya, and Pretoria, South Africa, demonstrated that a substantial proportion
      would be inclined to reduce their use of other HIV risk-reduction practices if
      they were taking pre-exposure prophylaxis (PrEP). To explore the motivations for
      their anticipated behavior change, we conducted qualitative interviews with 60
      women whose survey responses suggested they would be more likely to reduce condom
      use or have sex with a new partner if they were taking PrEP compared to if they
      were not taking PrEP. Three interrelated themes were identified: (1) "PrEP
      protects"--PrEP was perceived as an effective HIV prevention method that replaced
      the need for condoms; (2) condoms were a source of conflict in relationships, and
      PrEP would provide an opportunity to resolve or avoid this conflict; and (3)
      having sex without a condom or having sex with a new partner was necessary for
      receiving material goods and financial assistance--PrEP would provide reassurance
      in these situations. Many believed that PrEP alone would be a sufficient HIV risk
      reduction strategy. These findings suggest that participants' HIV risk-reduction
      intentions, if they were to use PrEP, were based predominately on their
      understanding of the high efficacy of PrEP and their experiences with the
      limitations of condoms. Enhanced counseling is needed to promote informed
      decision making and to ensure overall sexual health for women using PrEP for HIV
      prevention, particularly with respect to the prevention of pregnancy and other
      sexually transmitted infections when PrEP is used alone.

PMID- 26196412
TI  - Semitransparent Fully Air Processed Perovskite Solar Cells.
AB  - Semitransparent solar cells are highly attractive for application as power
      generating windows. In this work, we present semitransparent perovskite solar
      cells that employ conducting polymer poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) film as the
      transparent counter electrode. The PEDOT: PSS electrode is prepared by transfer
      lamination technique using plastic wrap as the transfer medium. The use of the
      transfer lamination technique avoids the damage of the CH3NH3PbI3 perovskite film
      by direct contact of PEDOT: PSS aqueous solution. The semitransparent perovskite
      solar cells yield a power conversion efficiency of 10.1% at an area of about 0.06
      cm(2) and 2.9% at an area of 1 cm(2). The device structure and the fabrication
      technique provide a facile way to produce semitransparent perovskite solar cells.

PMID- 26196413
TI  - Liver gender dimorphism--insights from quantitative morphology.
AB  - It was shown recently that many genes are differentially expressed in the liver
      of males and females, thus strengthening the concept of liver gender dimorphism.
      This dimorphism exists in many pathological scenarios, from regeneration to
      fibrosis, which has led to the development of gender hepatology. Nevertheless, it
      is still unknown if gender dimorphism occurs in the structure of the normal
      liver. In recent years, it has been shown that, compared with male, the female
      rat liver bears less fibrotic tissue, more Kupffer cells (per volume unit) and
      has higher hepatocellularity, including binucleated hepatocytes (per volume
      unit). Our hypothesis is that the human liver also hides a gender dimorphic
      pattern. Baseline differences in fibrotic tissue would contribute to explain
      severe liver fibrosis in men. As to the disparity of Kupffer cells, this would
      clarify the stronger response to post-surgery infections in women, and it could
      be equated when appraising the higher susceptibility to alcohol. Regarding
      differences in hepatocytes, they not only justify existing differences in some
      liver parameters (e.g., transaminases and bilirubin), but they could also account
      for the higher regenerative potential of the female liver. The structural
      dimorphism in the human liver would sustain the concept of gender hepatology and,
      eventually, should be considered in the context of liver transplantation. 

PMID- 26196409
TI  - The role of platelets in the recruitment of leukocytes during vascular disease.
AB  - Besides their role in the formation of thrombus during haemostasis, it is
      becoming clear that platelets contribute to a number of other processes within
      the vasculature. Indeed, the integrated function of the thrombotic and
      inflammatory systems, which results in platelet-mediated recruitment of
      leukocytes, is now considered to be of great importance in the propagation,
      progression and pathogenesis of atherosclerotic disease of the arteries. There
      are three scenarios by which platelets can interact with leukocytes: (1) during
      haemostasis, when platelets adhere to and are activated on sub-endothelial matrix
      proteins exposed by vascular damage and then recruit leukocytes to a growing
      thrombus. (2) Platelets adhere to and are activated on stimulated endothelial
      cells and then bridge blood borne leukocytes to the vessel wall and. (3) Adhesion
      between platelets and leukocytes occurs in the blood leading to formation of
      heterotypic aggregates prior to contact with endothelial cells. In the following
      review we will not discuss leukocyte recruitment during haemostasis, as this
      represents a physiological response to tissue trauma that can progress, at least
      in its early stages, in the absence of inflammation. Rather we will deal with
      scenarios 2 and 3, as these pathways of platelet-leukocyte interactions are
      important during inflammation and in chronic inflammatory diseases such as
      atherosclerosis. Indeed, these interactions mean that leukocytes possess means of
      adhesion to the vessel wall under conditions that may not normally be permissive
      of leukocyte-endothelial cell adhesion, meaning that the disease process may be
      able to bypass the regulatory pathways which would ordinarily moderate the
      inflammatory response. 

PMID- 26196415
TI  - Beyond the "Cinderella effect" : Life history theory and child maltreatment.
AB  - A central thesis of this paper is that understanding the nature of child
      maltreatment is so complex that no one disciplinary specialty is likely to be
      sufficient for the task. Although life history theory is the guiding principle
      for our analysis, we argue that an evolutionary explanation adds precision by
      incorporating empirical findings originating from the fields of anthropology;
      clinical, developmental, and social psychology; and sociology. Although
      evolutionary accounts of child maltreatment have been largely limited to the role
      of the coefficient of relatedness, the prospective reproductive value of a child,
      and the residual reproductive potential of parents, a case is made for expanding
      this basic application. An explanatory model is presented that describes how
      ecological conditions as well as parental and child traits interact to influence
      the degree of parental investment. As shown in the model, these various "marker
      variables" alter parental perceptions of the benefits and costs associated with
      child care and promote low-investment parenting, which leads to disrupted family
      management practices and to a downward-spiraling, self-perpetuating system of
      coercive family interaction, increased parental rejection of the child, and even
      lower parental investment. Child maltreatment is the ultimate outcome of this
      downward trajectory of family relations. 

PMID- 26196414
TI  - Polygyny and child growth in a traditional pastoral society : The case of the
      datoga of Tanzania.
AB  - In this paper I use measures of childhood growth to assess from both an
      evolutionary theoretical and an applied public health perspective the impact of
      polygyny on maternal-child welfare among the Datoga pastoralists of Tanzania. I
      report that the growth and body composition of children varies in such a way as
      to suggest that polygyny is not generally beneficial to women in terms of
      offspring quality. Cross-sectional analysis of covariance by maternal marriage
      status revealed that children of first and second wives in polygynous marriages
      grow relatively poorly, that this is correlated with maternal physical status,
      and that the pattern is not modified by household wealth. I discuss how the
      dynamics of sexual conflicts operating during the formation and maintenance of
      marriages may be important factors in the etiology of poor child growth in this
      population, leading to complex patterns of variation in anthropometric indicators
      of both women and children. The theoretical conclusion is that improved
      evolutionary models of polygyny should be designed to examine the potential for
      adaptive tradeoffs between the currencies of offspring quality and quantity for
      all types of parents in a polygynous population. The practical conclusion is that
      a better understanding of the relationships between marriage practices and health
      outcomes would assist in the development of culturally appropriate health and
      nutrition interventions. 

PMID- 26196416
TI  - Perceived crime severity and biological kinship.
AB  - Two predictions concerning the perceived severity of crimes can be derived from
      evolutionary theory. The first, arising from the theory of inclusive fitness, is
      that crimes in general should be viewed as more serious to the degree that the
      victim is genetically related to the perpetrator. The second, arising from the
      deleterious effects of inbreeding depression, is that heterosexual sexual
      coercion should be perceived as more serious the closer the genetic relationship
      of victim and perpetrator, particularly when the victim is a female of fertile
      age. Two hundred and thirty university students estimated the magnitude of the
      severity of brief crime descriptions in three separate studies. In the first two,
      the biological kinship of victim and perpetrator was varied, and in the third,
      the hypothetical genetic relatedness of the subject and the fictitious victim was
      varied. All three studies found the linear relationships between biological
      kinship and perceived crime severity predicted by theory. 

PMID- 26196417
TI  - Function of infant-directed speech.
AB  - The relationship between a biological process and a behavioral trait indicates a
      proximate mechanism by which natural selection can act. In that context,
      examining an aspect of infant health is one method of investigating the adaptive
      significance of infant-directed speech (ID speech), and it could help to explain
      the widespread use of this communication style. The correlation between infant
      growth and infant-directed speech is positive and significant, and provides a
      vehicle for testing evolutionary history hypotheses. 

PMID- 26196418
TI  - Biodiesel production from wet microalgae feedstock using sequential wet
      extraction/transesterification and direct transesterification processes.
AB  - Although producing biodiesel from microalgae seems promising, there is still a
      lack of technology for the quick and cost-effective conversion of biodiesel from
      wet microalgae. This study was aimed to develop a novel microalgal biodiesel
      producing method, consisting of an open system of microwave disruption, partial
      dewatering (via combination of methanol treatment and low-speed centrifugation),
      oil extraction, and transesterification without the pre-removal of the co
      solvent, using Chlamydomonas sp. JSC4 with 68.7 wt% water content as the
      feedstock. Direct transesterification with the disrupted wet microalgae was also
      conducted. The biomass content of the wet microalgae increased to 56.6 and 60.5
      wt%, respectively, after microwave disruption and partial dewatering. About 96.2%
      oil recovery was achieved under the conditions of: extraction temperature, 45
      degrees C; hexane/methanol ratio, 3:1; extraction time, 80 min.
      Transesterification of the extracted oil reached 97.2% conversion within 15 min
      at 45 degrees C and 6:1 solvent/methanol ratio with simultaneous Chlorophyll
      removal during the process. Nearly 100% biodiesel conversion was also obtained
      while conducting direct transesterification of the disrupted oil-bearing
      microalgal biomass.

PMID- 26196419
TI  - The role of pH control on biohydrogen production by single stage hybrid dark- and
      photo-fermentation.
AB  - The role of pH control on biohydrogen production by co-culture of dark
      fermentative Clostridium acetobutylicum and photofermentative Rhodobacter
      sphaeroides was studied. Single stage dark fermentation, photofermentation and
      hybrid co-culture systems were studied at different values of controlled and
      uncontrolled pH. Increasing pH during dark fermentation resulted in lower
      hydrogen production rate (HPR) and longer lag time for both controlled and
      uncontrolled conditions. However, it only slightly affected cumulative H2 volume.
      Results have shown that pH control at pH 7.5 increased photofermentative hydrogen
      production from 0.966 to 2.502 L H2/L(medium) when compared to uncontrolled
      process. Fixed pH value has proven to be an important control strategy also for
      the hybrid process and resulted in obtaining balanced co-culture of dark and
      photofermentative bacteria. Control of pH at 7.0 was found optimum for bacteria
      cooperation in the co-culture what resulted in obtaining 2.533 L H2/L(medium) and
      H2 yield of 6.22 mol H2/mol glucose.

PMID- 26196420
TI  - Experiment and simulation study on alkalis transfer characteristic during direct
      combustion utilization of bagasse.
AB  - Bagasse is utilized as fuel in the biggest biomass power plant of China, however,
      alkalis in the fuel created severe agglomeration and slagging problems. Alkalis
      transfer characteristic, agglomeration causes in engineering practice, additive
      improvement effects and mechanism during bagasse combustion were investigated via
      experiments and simulations. Only slight agglomeration occurs in ash higher than
      800 degrees C. Serious agglomeration in practical operation should be attributed
      to the gaseous alkalis evaporating at high temperature and condensing on the
      cooler grain surfaces in CFB. It can be speculated that ash caking can be avoided
      with temperature lower than 750 degrees C and heating surface corrosion caused by
      alkali metal vapor can be alleviated with temperature lower than 850 degrees C.
      Kaolin added into the bagasse has an apparent advantage over CaO additive both in
      enhancing ash fusion point and relieving alkali-chloride corrosion by locking
      alkalis in dystectic solid compounds over the whole temperature range. 

PMID- 26196421
TI  - Techno-economic analysis of decentralized biomass processing depots.
AB  - Decentralized biomass processing facilities, known as biomass depots, may be
      necessary to achieve feedstock cost, quantity, and quality required to grow the
      future U.S. bioeconomy. In this paper, we assess three distinct depot
      configurations for technical difference and economic performance. The depot
      designs were chosen to compare and contrast a suite of capabilities that a depot
      could perform ranging from conventional pelleting to sophisticated pretreatment
      technologies. Our economic analyses indicate that depot processing costs are
      likely to range from ~US$30 to US$63 per dry metric tonne (Mg), depending upon
      the specific technology implemented and the energy consumption for processing
      equipment such as grinders and dryers. We conclude that the benefits of
      integrating depots into the overall biomass feedstock supply chain will outweigh
      depot processing costs and that incorporation of this technology should be
      aggressively pursued. 

PMID- 26196422
TI  - Utilisation of sewage sludge derived adsorbents for the removal of recalcitrant
      compounds from wastewater: Mechanistic aspects, isotherms, kinetics and
      thermodynamics.
AB  - In the present study, the performance of sewage sludge based adsorbents was
      examined for the removal of two recalcitrant pollutants (i.e. lignin and
      amoxicillin) from synthetic wastewater solutions (adsorbate concentration=50-250
      mg/l). The effect of various reaction parameters such as wastewater pH, adsorbent
      dosage and temperature was studied. Possible mechanisms for the adsorption
      process have been proposed which depends upon the behaviour of adsorbent surface
      and adsorbate molecules under specific reaction conditions. Three-parameter
      Redlich-Peterson isotherm model was found the best fit to the equilibrium data.
      Pseudo first and second order models validated the kinetic data for lignin and
      amoxicillin adsorption systems, respectively and the corresponding activation
      energy was 3.5-4.5 and 12-22 kJ/mol. The nature of adsorption was elucidated from
      the thermodynamic parameters.

PMID- 26196423
TI  - The Emergence of Games for Health.

PMID- 26196425
TI  - Curiosity, Hope, and Vision: The Role of the Robert Wood Johnson Foundation's
      Pioneer Portfolio in Funding Early Health Game Research.
AB  - Games for Health Journal Editor Bill Ferguson recently discussed The Robert Wood
      Johnson Foundation's important role in funding health game research with Paul
      Tarini, Senior Program Officer for the Foundation's Pioneer Portfolio. 

PMID- 26196426
TI  - Games? Seriously! A Candid Conversation with Ben Sawyer, Co-Founder of
      Digitalmill.
AB  - I caught up with Ben Sawyer between his many presentations at conferences around
      the globe. I was first introduced to Ben and his amazing expertise and energy at
      the Games for Health Conference where he served as the organizer, Master of
      Ceremonies, and keynote speaker. For quite some time Ben has been known as one of
      the founding fathers of health games, and I was delighted to have the opportunity
      to learn more about his seminal efforts in the field. 

PMID- 26196427
TI  - Health Games Come of Age: An Expert Panel Discussion.

PMID- 26196428
TI  - The UnitedHealth Group and Gaming.

PMID- 26196429
TI  - Using an Avatar-Based Simulation to Train Families to Motivate Veterans with Post
      Deployment Stress to Seek Help at the VA.
AB  - OBJECTIVE: This study examines the effectiveness of "Family of Heroes," an online
      avatar-based post-deployment stress and resiliency training simulation, in
      increasing families' engagement in motivating their veterans who exhibit signs of
      post-deployment stress, including post-traumatic stress disorder (PTSD),
      traumatic brain injury (TBI), depression, and suicide ideation, to seek help at
      the Veterans Administration (VA). MATERIALS AND METHODS: Participants were
      randomly assigned to an experimental group (n=50) that completed the online
      training and pre- and post-intervention and 1-month follow-up surveys or a
      control group (n=44) who only completed a pre-test and a 1-month follow-up
      survey. RESULTS: The experimental group exhibited significantly greater changes
      in its preparedness and likelihood to recognize signs of post-deployment stress
      and in approaching their veteran to discuss their concern and motivate them to
      seek help at the VA. This group also reported significant change in actual
      behavior in terms of discussing their concern with their veteran (79 percent
      approached to discuss vs. 56 percent for the control group). Finally, seven (22
      percent) of the veterans who were approached by the experimental group started to
      receive mental health treatment (five at the VA). All seven were previously
      diagnosed with PTSD and/or depression but never before started treatment at the
      VA. CONCLUSION: Results strongly suggest that "Family of Heroes" is an effective
      tool to engage families in taking an active role in motivating their veterans who
      exhibit signs of post-deployment stress to seek help at the VA. Results also
      suggest that the training can increase the actual number of veterans experiencing
      post-deployment stress who begin to receive treatment at the VA.

PMID- 26196430
TI  - Pilot Study of an Active Screen Time Game Correlates with Improved Physical
      Fitness in Minority Elementary School Youth.
AB  - OBJECTIVE: The aim of our feasibility study was to examine the acceptability and
      utility of "Dance Dance Revolution" (DDR) (Konami of America, Redwood City, CA))
      to increase physical fitness in 8-11-year-old black and Hispanic youth. SUBJECTS
      AND METHODS: Twenty-eight 4(th) and 5(th) grade children attending an afterschool
      program participated. Outcomes included physical activity, physical fitness, use
      of home DDR, survey of safety and acceptability, anthropometrics, and fasting
      metabolic profile measured at baseline, 12 weeks, and 30 weeks. RESULTS: At 12
      weeks, physical fitness (maximum O2 uptake [VO2max]) increased by 4.9+/-9.9
      percent and was sustained through 30 weeks, when the VO2max was 105.0+/-9.9
      percent (range, 93.0-133.9 percent) of baseline values. Absolute VO2max increased
      by 2.97+/-4.99 mL/kg/minute (95% confidence interval 0.75-5.19, P=0.013).
      Participants maintained an average of 1.12 hours/day of increased movement to
      music. Trends suggested increased total moderate-vigorous physical activity,
      decreased light activity, and a modest increase in sedentary screen time. There
      were no significant changes in body mass index, fasting lipids, or glucose.
      Participants and parents approved of the activity. CONCLUSION: DDR appears
      feasible and acceptable to minority youth. DDR may increase moderate-vigorous
      physical activity and improve physical fitness in at-risk populations.

PMID- 26196431
TI  - "Dance Dance Revolution" Used by 7- and 8-Year-Olds to Boost Physical Activity:
      Is Coaching Necessary for Adherence to an Exercise Prescription?
AB  - OBJECTIVE: To increase opportunities for physical activity (PA) for children in
      children's homes, we used a "Dance Dance Revolution" (DDR) (Konami of America,
      Redwood City, CA) coaching protocol for 7- and 8-year-olds. SUBJECTS AND METHODS:
      We randomly assigned youth to either an Enhanced (coaching) or Basic (no
      coaching) group. A DDR prescription of 120 minutes/week was provided to 40
      children. Motor learning principles guided the coaching protocol, provided by
      adult graduate students, which took place weekly during weeks 1-5. PA was
      measured with accelerometry, DDR logs, and Sony (New York, NY) Playstation((r))2
      memory cards at baseline and at week 10. RESULTS: Total accelerometer-measured PA
      was not significantly different between the groups at baseline or week 10;
      however, vigorous PA increased significantly in both groups at week 10. DDR logs
      showed a large range from 0 to 660 minutes/week of dance time. Respective playing
      time for each week (1 and 10) averaged 149 and 64 minutes for the Basic group and
      184 and 47 minutes for the Enhanced group. Coaching significantly increased DDR
      use patterns in this population of youngsters during weeks 1 through 5 (P<0.001).
      CONCLUSION: Adult coaching deserves further study to determine how to maintain
      high levels of participation in exergames for youth who live in an obesogenic
      environment.

PMID- 26196432
TI  - Results of a Dietitian Survey About Nutrition Games.
AB  - OBJECTIVE: Registered dietitians are the nutrition experts in America. As such,
      their opinions about using technology-based nutrition games as teaching tools are
      important. The purpose of this study was to query registered dietitians about
      their experience and recommendations for topics, age, and platforms for future
      nutrition game development. MATERIALS AND METHODS: The author gave a 1-hour talk
      to two state dietetic conference groups about nutrition games and their efficacy,
      concerns, and hopes and opportunities for their future as viable nutrition
      teaching tools. After the talks attendees completed a five-question survey about
      nutrition games, including if they played nutrition games, if they thought games
      could possibly help in their work, and preferences for topics, ages, and
      platforms for which they wanted to see priority development. RESULTS: Although
      only 4% of respondents played nutrition games, 79% thought they could be of
      benefit, and 21% felt that "maybe" they could be beneficial educational tools.
      Games on all nutrition topics were welcome, with preference for computers and
      smartphone apps. CONCLUSION: After a lengthy presentation on the new genre of
      technology-based nutrition games, registered dietitians reported that they are
      open to using technology-based nutrition education apps and feel they could have
      some benefit in educating the public about nutrition, even though dietitians
      presently have little experience with them. The talk was successful in informing
      dietitians about this new game genre, and their suggestions for topics, target
      ages, and tech platforms will be helpful to nutrition game developers and
      designers.

PMID- 26196433
TI  - Comparing Energy Expenditure in Adolescents With and Without Autism While Playing
      Nintendo((r)) Wii(TM) Games.
AB  - OBJECTIVE: Obesity rates are on the rise in individuals with autism spectrum
      disorders (ASD), which underscores the importance of finding new ways in which to
      engage this population in physical activity. We wanted to explore the energetic
      expenditure of adolescents with and without ASD while playing Nintendo((r))
      Wii(TM) (Nintendo of America, Inc., Redmond, WA) games compared with more
      traditional exercise modalities. Specifically, we wanted to compare energy
      expenditure (EE) among the different activities and to see which activities lead
      to the greatest amount of time classified as "moderate to vigorous." SUBJECTS AND
      METHODS: Two groups of adolescents (15 with ASD [mean age, 17.50+/-2.4 years], 15
      without ASD [mean age, 17.23+/-4.1 years]) participated in 20-minute bouts of
      walking, running, and playing Nintendo Wii "Sport(TM)," Wii "Fit(TM)," and "Dance
      Dance Revolution" (DDR) (Konami Digital Entertainment, Inc., El Segundo, CA).
      During each session, EE was calculated using an Actical (Mini Mitter Co., Bend,
      OR) accelerometer. Groups were compared using multiple t tests. RESULTS: Both
      groups expended similar amounts of kilcalories in all activities, except for Wii
      Fit, in which the ASD group expended significantly more kilocalories. For the ASD
      group, EE was greatest in running, followed by walking, DDR, Wii Fit, and Wii
      Sport. Walking, running, and DDR all had at least 75 percent of the total time
      spent in moderate to vigorous intensity levels. CONCLUSION: We suggest videogame
      systems, such as the Nintendo Wii, may be viable alternative for individuals with
      ASD to increase their daily physical activity and help alleviate the growing
      rates of obesity.

PMID- 26196434
TI  - Use of Nintendo((r)) Wii(TM) in Physical Therapy of an Adult with Lower Extremity
      Burns.
AB  - OBJECTIVE: The purpose of this exploratory case study is to describe differences
      in rehabilitation outcomes for a 47-year-old male with bilateral lower extremity
      burns when using conventional therapy techniques alone versus such techniques in
      combination with Nintendo((r)) WiiTM (Nintendo of America, Inc., Redmond, WA)
      videogames. MATERIALS AND METHODS: The patient received three series of
      rehabilitation therapy over 2 weeks. During the second series, the Wii was
      introduced for a portion of the otherwise conventional therapy. Under
      standardized conditions and upon completion of each series, the Limits of
      Stability test with a SMART Balance Master((r)) (NeuroCom((r)), Clackamas, OR)
      was used to measure reaction time (RT), maximum excursion (MXE), endpoint
      excursion (EPE), movement velocity, and directional control. The Timed Up and Go
      (TUG) test for functional mobility and a questionnaire assessing level of
      motivation and interest were administered at the end of each day; these results
      formed mean scores for each series. RESULTS: The patient performed better on RT
      and MXE during the series that combined conventional therapy with the Wii than
      during the two series using conventional therapy alone. Improvement on EPE was
      greater for combined therapy than for conventional therapy alone and continued to
      improve after combined therapy. The patient completed the TUG test faster during
      the combined Wii series. Additionally, the patient reported increased motivation
      and interest levels for the series using combined therapy. CONCLUSIONS: The Wii
      may be a feasible and valuable adjunct to traditional therapy. Improvements
      during the series with Wii were demonstrated for areas of balance and functional
      mobility. Trends toward improvement in motivation and interest with the Wii
      suggest its use may elicit increased patient engagement during burn
      rehabilitation.

PMID- 26196435
TI  - Project Injini: Developing Cognitive Training Games for Children with Special
      Needs.
AB  - With the advent of the Apple iPad((r)), learning applications (apps) have enabled
      children with special needs to have easy access to the technological benefits of
      computer-based learning. As the iPad was introduced into therapy for these
      children, we at Project Injini saw the potential for extending early intervention
      to therapeutic play at home. We developed the Injini Child Development Game Suite
      with specific guidelines in mind to design an app appropriate for children's
      abilities and needs. We field-tested Injini at schools and centers for
      disabilities to receive feedback. This article describes the initial results of
      these efforts. 

PMID- 26196436
TI  - Evaluating Efficacy and Validating Games for Health.
AB  - The field of games for health is growing rapidly, but many games for health are
      not validated for their use as a tool to improve outcomes. The few research
      studies that do exist are often poorly designed, and their conclusions cannot be
      considered valid evidence to support or refute efficacy. Based on lessons learned
      from the field of digital game-based learning in education and recent efforts to
      systematically review games for health in meta-analyses, guidelines are suggested
      for conducting high-quality efficacy studies on games for health. 

PMID- 26196437
TI  - Reality Is Broken by J. McGonigal.

PMID- 26196438
TI  - Behavioral inhibition in childhood predicts smaller hippocampal volume in
      adolescent offspring of parents with panic disorder.
AB  - Behavioral inhibition (BI) is a genetically influenced behavioral profile seen in
      15-20% of 2-year-old children. Children with BI are timid with people, objects
      and situations that are novel or unfamiliar, and are more reactive
      physiologically to these challenges as evidenced by higher heart rate, pupillary
      dilation, vocal cord tension and higher levels of cortisol. BI predisposes to the
      later development of anxiety, depression and substance abuse. Reduced hippocampal
      volumes have been observed in anxiety disorders, depression and posttraumatic
      stress disorder. Animal models have demonstrated that chronic stress can damage
      the hippocampal formation and implicated cortisol in these effects. We,
      therefore, hypothesized that the hippocampi of late adolescents who had been
      behaviorally inhibited as children would be smaller compared with those who had
      not been inhibited. Hippocampal volume was measured with high-resolution
      structural magnetic resonance imaging in 43 females and 40 males at 17 years of
      age who were determined to be BI+ or BI- based on behaviors observed in the
      laboratory as young children. BI in childhood predicted reduced hippocampal
      volumes in the adolescents who were offspring of parents with panic disorder, or
      panic disorder with comorbid major depression. We discuss genetic and
      environmental factors emanating from both child and parent that may explain these
      findings. To the best of our knowledge, this is the first study to demonstrate a
      relationship between the most extensively studied form of temperamentally based
      human trait anxiety, BI, and hippocampal structure. The reduction in hippocampal
      volume, as reported by us, suggests a role for the hippocampus in human trait
      anxiety and anxiety disorder that warrants further investigation. 

PMID- 26196439
TI  - The oxytocin system promotes resilience to the effects of neonatal isolation on
      adult social attachment in female prairie voles.
AB  - Genes and social experiences interact to create variation in social behavior and
      vulnerability to develop disorders of the social domain. Socially monogamous
      prairie voles display remarkable diversity in neuropeptide receptor systems and
      social behavior. Here, we examine the interaction of early-life adversity and
      brain oxytocin receptor (OTR) density on adult social attachment in female
      prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from
      postnatal day 1-14. Adult subjects were tested on the partner preference (PP)
      test to assess social attachment and OTR density in the brain was quantified.
      Neonatal social isolation impaired female PP formation, without affecting OTR
      density. Accumbal OTR density was, however, positively correlated with the
      percent of time spent huddling with the partner in neonatally isolated females.
      Females with high accumbal OTR binding were resilient to neonatal isolation.
      These results are consistent with the hypothesis that parental nurturing shapes
      neural systems underlying social relationships by enhancing striatal OTR
      signaling. Thus, we next determined whether early touch, mimicking parental
      licking and grooming, stimulates hypothalamic OT neuron activity. Tactile
      stimulation induced immediate-early gene activity in OT neurons in neonates.
      Finally, we investigated whether pharmacologically potentiating OT release using
      a melanocortin 3/4 agonist, melanotan-II (10 mg kg(-1) subcutaneously), would
      mitigate the social isolation-induced impairments in attachment behavior.
      Neonatal melanotan-II administration buffered against the effects of early
      isolation on partner preference formation. Thus, variation in accumbal OTR
      density and early OT release induced by parental nurturing may moderate
      susceptibility to early adverse experiences, including neglect.

PMID- 26196440
TI  - Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia.
AB  - Genetic associations involving both rare and common alleles have been reported
      for schizophrenia but there have been no systematic scans for rare recessive
      genotypes using fully phased trio data. Here, we use exome sequencing in 604
      schizophrenia proband-parent trios to investigate the role of recessive
      (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder.
      The burden of recessive genotypes was not significantly increased in probands at
      either a genome-wide level or in any individual gene after adjustment for
      multiple testing. At a system level, probands had an excess of nonsynonymous
      compound heterozygous genotypes (minor allele frequency, MAF ? 1%) in voltage
      gated sodium channels (VGSCs; eight in probands and none in parents, P = 1.5 *
      10(-)(4)). Previous findings of multiple de novo loss-of-function mutations in
      this gene family, particularly SCN2A, in autism and intellectual disability
      provide biological and genetic plausibility for this finding. Pointing further to
      the involvement of VGSCs in schizophrenia, we found that these genes were
      enriched for nonsynonymous mutations (MAF ? 0.1%) in cases genotyped using an
      exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios
      data, synaptic proteins interacting with VGSCs were also enriched for both
      compound heterozygosity (P = 0.018) and de novo mutations (P = 0.04). However, we
      were unable to replicate the specific association with compound heterozygosity at
      VGSCs in an independent sample of Taiwanese schizophrenia trios (N = 614). We
      conclude that recessive genotypes do not appear to make a substantial
      contribution to schizophrenia at a genome-wide level. Although multiple lines of
      evidence, including several from this study, suggest that rare mutations in VGSCs
      contribute to the disorder, in the absence of replication of the original
      findings regarding compound heterozygosity, this conclusion requires evaluation
      in a larger sample of trios.

PMID- 26196441
TI  - Acidic Residues in the Hfq Chaperone Increase the Selectivity of sRNA Binding and
      Annealing.
AB  - Hfq facilitates gene regulation by small non-coding RNAs (sRNAs), thereby
      affecting bacterial attributes such as biofilm formation and virulence.
      Escherichia coli Hfq recognizes specific U-rich and AAN motifs in sRNAs and
      target mRNAs, after which an arginine patch on the rim promotes base pairing
      between their complementary sequences. In the cell, Hfq must discriminate between
      many similar RNAs. Here, we report that acidic amino acids lining the sRNA
      binding channel between the inner pore and rim of the Hfq hexamer contribute to
      the selectivity of Hfq's chaperone activity. RNase footprinting, in vitro binding
      and stopped-flow fluorescence annealing assays showed that alanine substitution
      of D9, E18 or E37 strengthened RNA interactions with the rim of Hfq and increased
      annealing of non-specific or U-tailed RNA oligomers. Although the mutants were
      less able than wild-type Hfq to anneal sRNAs with wild-type rpoS mRNA, the D9A
      mutation bypassed recruitment of Hfq to an (AAN)4 motif in rpoS, both in vitro
      and in vivo. These results suggest that acidic residues normally modulate access
      of RNAs to the arginine patch. We propose that this selectivity limits
      indiscriminate target selection by E. coli Hfq and enforces binding modes that
      favor genuine sRNA and mRNA pairs. 

PMID- 26196443
TI  - Natalizumab for Crohn's Disease: Down but Not Out.

PMID- 26196444
TI  - Reply: To PMID 25460554.

PMID- 26196442
TI  - The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather
      Follicle Regeneration.
AB  - Hair and feathers are unique because (1) their stem cells are contained within a
      follicle structure, (2) they undergo cyclic regeneration repetitively throughout
      life, (3) regeneration occurs physiologically in healthy individuals and (4)
      regeneration is also induced in response to injury. Precise control of this
      cyclic regeneration process is essential for maintaining the homeostasis of
      living organisms. While stem cells are regulated by the intra-follicle-adjacent
      micro-environmental niche, this niche is also modulated dynamically by extra
      follicular macro-environmental signals, allowing stem cells to adapt to a larger
      changing environment and physiological needs. Here we review several examples of
      macro-environments that communicate with the follicles: intradermal adipose
      tissue, innate immune system, sex hormones, aging, circadian rhythm and seasonal
      rhythms. Related diseases are also discussed. Unveiling the mechanisms of how
      stem cell niches are modulated provides clues for regenerative medicine. Given
      that stem cells are hard to manipulate, focusing translational therapeutic
      applications at the environments appears to be a more practical approach. 

PMID- 26196445
TI  - Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is
      Associated With Nonalcoholic Fatty Liver Disease.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) can develop in individuals
      without cirrhosis. We investigated risk factors for development of HCC in the
      absence of cirrhosis in a U.S. METHODS: We identified a national cohort of 1500
      patients with verified HCC during 2005 to 2010 in the U.S. Veterans
      Administration (VA) and reviewed their full VA medical records for evidence of
      cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to
      categories of level 1 evidence for no cirrhosis (very high probability) or level
      2 evidence for no cirrhosis (high probability), which were based on findings from
      histologic analyses, laboratory test results, markers of fibrosis from
      noninvasive tests, and imaging features. RESULTS: A total of 43 of the 1500
      patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%)
      had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had
      confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis,
      greater proportions of patients with HCC without evidence of cirrhosis had
      metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable
      risk factors. Patients with HCC without evidence of cirrhosis were less likely to
      have abused alcohol or have hepatitis C virus infection than patients with
      cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95%
      confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0;
      95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the
      absence of cirrhosis, compared with patients with HCV-related HCC. CONCLUSIONS:
      Approximately 13% of patients with HCC in the VA system do not appear to have
      cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the
      absence of cirrhosis.

PMID- 26196446
TI  - Reply: To PMID 25632807.

PMID- 26196447
TI  - Lassa Virus in Multimammate Rats, Cote d'Ivoire, 2013.

PMID- 26196449
TI  - The Fading Affect Bias shows healthy coping at the general level, but not the
      specific level for religious variables across religious and non-religious events.
AB  - The research on fading emotions has shown that unpleasant emotions fade more over
      time than pleasant emotions, which is a phenomenon referred to as the Fading
      Affect Bias (FAB). Based on the negative relation between the FAB and dysphoria
      (Walker, Skowronski, Gibbons, Vogl, & Thompson, 2003), some researchers have
      argued that the FAB is a healthy coping mechanism (Walker, Skowronski, &
      Thompson, 2003). As religious variables are related to positive emotions and
      emotional coping (e.g., Cohen, 2002; Pargament, Smith, Koenig, & Perez, 1998), we
      examined the FAB as a healthy coping mechanism at the general and specific levels
      of analysis in the context of religion. General healthy coping was supported by
      (1) FAB effects across both religious events (REs) and non-religious events
      (NREs) and (2) a positive relation for spirituality and the FAB. However,
      specific healthy coping was not supported by a small FAB for (1) REs at high
      levels of positive religious coping (PRC) for NREs, (2) NREs at low levels of PRC
      for NREs, and (3) purely REs relative to REs involving spirituality. Other
      implications are discussed. 

PMID- 26196450
TI  - The role of agency for perceived ownership in the virtual hand illusion.
AB  - The rubber hand illusion shows that people can perceive artificial effectors as
      part of their own body under suitable conditions, and the virtual hand illusion
      shows the same for virtual effectors. In this study, we compared a virtual
      version of the rubber-hand setup with a virtual-hand setup, and manipulated the
      synchrony between stimulation or movement of a virtual "effector" and stimulation
      or movement of people's own hand, the similarity between virtual effector and
      people's own hand, and the degree of agency (the degree to which the virtual
      effector could be controlled by people's own movements). Synchrony-induced
      ownership illusion was strongly affected by agency but not similarity, which is
      inconsistent with top-down modulation approaches but consistent with bottom-up
      approaches to ownership. However, both agency and similarity induce a general
      bias towards perceiving an object as part of one's body, suggesting that
      ownership judgments integrate various sources of information. 

PMID- 26196448
TI  - Effects of Different Doses of Nucleocapsid Protein from Hantaan Virus A9 Strain
      on Regulation of Interferon Signaling.
AB  - Hantaan virus A9 strain (HTNV A9) is an etiologic agent of hemorrhagic fever with
      renal syndrome in China. The virulence of the pathogenic hantaviruses is
      determined by their ability to alter key signaling pathways of early interferon
      (IFN) induction within cells. The potential role of HTNV A9 structural proteins,
      such as nucleocapsid (N) and envelope glycoproteins (Gn and Gc), in regulating
      human's innate antiviral immune response has not yet been clarified. In this
      study, we investigated the effect of HTNV A9 N protein on the regulation of the
      IFN pathway. We found that A9 N protein can influence the host innate immune
      response by regulating the activation of IFNbeta. The A9 N protein stimulates IFN
      response in low doses, whereas significantly inhibits IFNbeta production at high
      doses. Furthermore, A9 N protein constitutively inhibits nuclear factor kappa B
      activation. A high dose of A9 N protein could inhibit either Poly IC-induced
      IFNbeta or vesicular stomatitis virus-induced IFNbeta and interferon-stimulated
      gene production. Our results indicate that HTNV A9 N protein helps virus
      establish successful infection by downregulating the IFN response and shed new
      light to the understanding of the interaction between the host innate immunity
      and virus during Hantaan virus infection. 

PMID- 26196451
TI  - A new steroidal glycoside from Corypha taliera Roxb., a globally endangered
      species.
AB  - A new steroidal glycoside, beta-sitosterol-3-O-alpha-L-rhamnopyranosyl-(1->4)
      beta-D-xylopyranosyl-(1->4)-beta-D-glucopyranosyl-(1->4)-beta-D-glucopyranoside
      was isolated from the methanol extract of the pericarp of Corypha taliera Roxb.
      The reversed-phased HPLC analysis of the methanol extract of the pericarp of C.
      taliera Roxb. (Talipalm), a rare species of Arecaceae family, afforded a new
      steroidal glycoside, beta-sitosterol-3-O-alpha-L-rhamnopyranosyl-(1->4)-beta-D
      xylopyranosyl-(1->4)-beta-D-glucopyranosyl-(1->4)-beta-D-glucopyranoside (1). The
      structure of the compound was elucidated unequivocally by UV, IR, HR-ESI-MS, (1)H
      and (13)C NMR spectroscopic studies.

PMID- 26196452
TI  - Infectious origins of childhood leukemia.

PMID- 26196453
TI  - Hydroxylated fullerene: a potential antiinflammatory and antioxidant agent for
      preventing mouse preterm birth.
AB  - OBJECTIVE: Intrauterine infection such as by Escherichia coli and Ureaplasma spp
      induce placental inflammation and are one of the leading causes of preterm birth.
      Here we evaluated hydroxylated fullerene (C60[OH]44) for its in vitro
      antiinflammatory and antioxidant effects against host cellular responses to the
      ureaplasma toll-like receptor 2 (TLR2) ligand, UPM-1. In addition, we
      investigated the preventative effects of C60(OH)44 in vivo in a mouse preterm
      birth model that used UPM-1. STUDY DESIGN: TLR2-overexpressing cell lines and the
      primary cultures of mouse peritoneal macrophages were pretreated with C60(OH)44.
      After UPM-1 addition to the cell lines, the activation of the nuclear factor
      kappa-light chain-enhancer of activated B cells (NF-kappaB) signaling cascade and
      the production of reactive oxygen species were monitored. The levels of
      expression of inflammatory cytokines of interleukin (IL)-6, IL-1beta, tumor
      necrosis factor (TNF)-alpha, and the production of reactive oxygen species were
      quantified after stimulation with UPM-1. The in vivo preventative effects of
      C60(OH)44 on mice preterm birth were evaluated by analyzing the preterm birth
      rates and fetal survival rates in the preterm birth mouse model with placental
      histological analyses. RESULTS: Pretreatment with C60(OH)44 significantly
      suppressed UPM-1-induced NF-kappaB activation and reactive oxygen species
      production in TLR2-overexpressing cell lines. In the primary culture of mouse
      peritoneal macrophages, UPM-1-induced production of reactive oxygen species and
      the expression of inflammatory cytokines such as IL-6, IL-1beta, and TNF-alpha
      were significantly reduced by pretreatment with C60(OH)44. In the UPM-1-induced
      preterm birth mouse model, the preterm birth rate decreased from 72.7% to 18.2%
      after an injection of C60(OH)44. Placental examinations of the group injected
      with C60(OH)44 reduced the damage of the spongiotrophoblast layer and reduced
      infiltration of neutrophils. CONCLUSION: C60(OH)44 was effective as a
      preventative agent of preterm birth in mice.

PMID- 26196454
TI  - Effect of time of birth on maternal morbidity during childbirth hospitalization
      in California.
AB  - OBJECTIVE: This observational study aimed to determine the relationship between
      time of birth and maternal morbidity during childbirth hospitalization. STUDY
      DESIGN: Composite maternal morbidities were determined using International
      Classification of Diseases, Ninth Revision, Clinical Modification and vital
      records codes, using linked hospital discharge and vital records data for
      1,475,593 singleton births in California from 2005 through 2007. Time of birth,
      day of week, and sociodemographic, obstetric, and hospital volume risk factors
      were estimated using mixed effects logistic regression models. RESULTS: The odds
      for pelvic morbidity were lowest between 11 PM-7 AM compared to other time
      periods and the reference value of 7-11 AM. The odds for pelvic morbidity peaked
      between 11 AM-7 PM (adjusted odds ratio [AOR], 1101-1500 = 1.07; 95% confidence
      interval [CI], 1.06-1.09; 1501-1900 = 1.08; 95% CI, 1.06-1.10). Odds for severe
      morbidity were higher between 11 PM-7 AM (AOR, 2301-0300 = 1.31; 95% CI, 1.21
      1.41; 0301-0700 = 1.30; 95% CI, 1.20-1.41) compared to other time periods. The
      adjusted odds were not statistically significant for weekend birth on pelvic
      morbidity (AOR, Saturday = 1.00; 95% CI, 0.98-1.02]; Sunday = 1.01; 95% CI, 0.99
      1.03) or severe morbidity (AOR, Saturday = 1.09; 95% CI, 1.00-1.18; Sunday =
      1.03; 95% CI, 0.94-1.13). Cesarean birth, hypertensive disorders, birthweight,
      and sociodemographic factors that include age, race, ethnicity, and insurance
      status were also significantly associated with severe morbidity. CONCLUSION: Even
      after controlling for sociodemographic factors and known risks such as cesarean
      birth and pregnancy complications such as hypertensive disorders, birth between
      11 PM-7 AM is a significant independent risk factor for severe maternal
      morbidity.

PMID- 26196455
TI  - Cross-sectional survey of California childbirth hospitals: implications for
      defining maternal levels of risk-appropriate care.
AB  - OBJECTIVE: Measures of maternal mortality and severe maternal morbidity have
      risen in the United States, sparking national interest regarding hospitals'
      ability to provide maternal risk-appropriate care. We examined the extent to
      which hospitals could be classified by increasingly sophisticated maternal levels
      of care. STUDY DESIGN: We performed a cross-sectional survey to identify hospital
      specific resources and classify hospitals by criteria for basic, intermediate,
      and regional maternal levels of care in all nonmilitary childbirth hospitals in
      California. We measured hospital compliance with maternal level of care criteria
      that were produced via consensus based on professional standards at 2 regional
      summits funded by the March of Dimes through a cooperative agreement with the
      Community Perinatal Network in 2007 (California Perinatal Summit on Risk
      Appropriate Care). RESULTS: The response rate was 96% (239 of 248 hospitals).
      Only 82 hospitals (34%) were classifiable under these criteria (35 basic, 42
      intermediate, and 5 regional) because most (157 [66%]) did not meet the required
      set of basic criteria. The unmet criteria preventing assignment into the basic
      category included the ability to perform a cesarean delivery within 30 minutes
      100% of the time (only 64% met), pediatrician availability day and night (only
      56% met), and radiology department ultrasound capability within 12 hours (only
      83% met). Only 29 of classified hospitals (35%) had a nursery or neonatal
      intensive care unit level that matched the maternal level of care, and for most
      remaining hospitals (52 of 53), the neonatal intensive care unit level was higher
      than the maternal care level. CONCLUSION: Childbirth services varied widely
      across California hospitals, and most hospitals did not fit easily into proposed
      levels. Cognizance of this existing variation is critical to determining the
      optimal configuration of services for basic, intermediate, and regional maternal
      levels of care.

PMID- 26196456
TI  - Effect of delayed cord clamping on very preterm infants.
AB  - OBJECTIVE: Despite significant proposed benefits, delayed umbilical cord clamping
      (DCC) is not practiced widely in preterm infants largely because of the question
      of feasibility of the procedure and uncertainty regarding the magnitude of the
      reported benefits, especially intraventricular hemorrhage (IVH) vs the adverse
      consequences of delaying the neonatal resuscitation. The objective of this study
      was to determine whether implementation of the protocol-driven DCC process in our
      institution would reduce the incidence of IVH in very preterm infants without
      adverse consequences. STUDY DESIGN: We implemented a quality improvement process
      for DCC the started in August 2013 in infants born at <=32 weeks' gestational
      age. Eligible infants were left attached to the placenta for 45 seconds after
      birth. Neonatal process and outcome data were collected until discharge. We
      compared infants who received DCC who were born between August 2013 and August
      2014 with a historic cohort of infants who were born between August 2012 and
      August 2013, who were eligible to receive DCC, but whose cord was clamped
      immediately after birth, because they were born before the protocol
      implementation. RESULTS: DCC was performed on all the 60 eligible infants; 88
      infants were identified as historic control subjects. Gestational age,
      birthweight, and other demographic variables were similar between both groups.
      There were no differences in Apgar scores or admission temperature, but
      significantly fewer infants in the DCC cohort were intubated in delivery room,
      had respiratory distress syndrome, or received red blood cell transfusions in the
      first week of life compared with the historic cohort. A significant reduction was
      noted in the incidence of IVH in the DCC cohort compared with the historic
      control group (18.3% vs 35.2%). After adjustment for gestational age, an
      association was found between the incidence of IVH and DCC with IVH was
      significantly lower in the DCC cohort compared with the historic cohort; an odds
      ratio of 0.36 (95% confidence interval, 0.15-0.84; P < .05). There were no
      significant differences in deaths and other major morbidities. CONCLUSION: DCC,
      as performed in our institution, was associated with significant reduction in IVH
      and early red blood cell transfusions. DCC in very preterm infants appears to be
      safe, feasible, and effective with no adverse consequences.

PMID- 26196457
TI  - Calcified plaque ablated by rotational atherectomy visualised by optical
      coherence tomography.

PMID- 26196458
TI  - Transcatheter occlusion with an AmplatzerTM Vascular Plug II for incomplete
      surgical ligation of left atrial appendage.

PMID- 26196459
TI  - The dopaminergic response to acute stress in health and psychopathology: A
      systematic review.
AB  - Previous work in animals has shown that dopamine (DA) in cortex and striatum
      plays an essential role in stress processing. For the first time, we
      systematically reviewed the in vivo evidence for DAergic stress processing in
      health and psychopathology in humans. All studies included (n studies=25, n
      observations=324) utilized DA D2/3 positron emission tomography and measured
      DAergic activity during an acute stress challenge. The evidence in healthy
      volunteers (HV) suggests that physiological, but not psychological, stress
      consistently increases striatal DA release. Instead, increased medial prefrontal
      cortex (mPFC) DAergic activity in HV was observed during psychological stress.
      Across brain regions, stress-related DAergic activity was correlated with the
      physiological and psychological intensity of the stressor. The magnitude of
      stress-induced DA release was dependent on rearing conditions, personality traits
      and genetic variations in several SNPs. In psychopathology, preliminary evidence
      was found for stress-related dorsal striatal DAergic hyperactivity in psychosis
      spectrum and a blunted response in chronic cannabis use and pain-related
      disorders, but results were inconsistent. Physiological stress-induced DAergic
      activity in striatum in HV may reflect somatosensory properties of the stressor
      and readiness for active fight-or-flight behavior. DAergic activity in HV in the
      ventral striatum and mPFC may be more related to expectations about the stressor
      and threat evaluation, respectively. Future studies with increased sample size in
      HV and psychopathology assessing the functional relevance of stress-induced
      DAergic activity, the association between cortical and subcortical DAergic
      activity and the direct comparison of different stressors are necessary to
      conclusively elucidate the role of the DA system in the stress response. 

PMID- 26196460
TI  - Prediction of spontaneous closure of traumatic macular hole with spectral domain
      optical coherence tomography.
AB  - It has been known that some traumatic macular holes can close spontaneously.
      However, knowledge about the types of macular hole that can close spontaneously
      is limited. In this retrospective study, we investigated patients with traumatic
      macular hole who were followed-up for at least 6 months without any surgical
      intervention. Clinical data and spectral domain optical coherence tomography (SD
      OCT) images were compared between groups with and without macular hole closure.
      Overall, 27 eyes were included. Spontaneous closure of macular hole was observed
      in 10 (37.0%) eyes. The holes with spontaneous closure had smaller minimum
      diameter (244.9 +/- 114.4 vs. 523.9 +/- 320.0 MUm, p = 0.007) and less
      intraretinal cysts (10% vs. 76.5%, p = 0.001) compared to the holes that did not
      close spontaneously. The area under the curve of receiver operative
      characteristic was 0.812 and 0.832 for minimum diameter of macular hole and
      presence of intraretinal cysts respectively. Multivariate logistic regression
      showed that the presence of intraretinal cysts was an independent predictive
      factor for closure of macular holes. The group with spontaneous macular hole
      closure had a high chance of visual improvement. Our study suggests that the
      absence of intraretinal cysts on SD-OCT can predict spontaneous closure of
      traumatic macular hole. 

PMID- 26196461
TI  - Response Strategies against Meningitis Epidemics after Elimination of Serogroup A
      Meningococci, Niger.
AB  - To inform epidemic response strategies for the African meningitis belt after a
      meningococcal serogroup A conjugate vaccine was introduced in 2010, we compared
      the effectiveness and efficiency of meningitis surveillance and vaccine response
      strategies at district and health area levels using various thresholds of weekly
      incidence rates. We analyzed reports of suspected cases from 3 regions in Niger
      during 2002-2012 (154,392 health area weeks), simulating elimination of serogroup
      A meningitis by excluding health area years with identification of such cases.
      Effectiveness was highest for health area surveillance and district vaccination
      (58-366 cases; thresholds 7-20 cases/100,000 doses), whereas efficiency was
      optimized with health area vaccination (5.6-7.7 cases/100,000 doses). District
      level intervention prevented <6 cases (0.2 cases/100,000 doses). Reducing the
      delay between epidemic signal and vaccine protection by 2 weeks doubled
      efficiency. Subdistrict surveillance and response might be most appropriate for
      meningitis epidemic response after elimination of serogroup A meningitis. 

PMID- 26196462
TI  - Plasticity in the High Affinity Menaquinone Binding Site of the Cytochrome aa3
      600 Menaquinol Oxidase from Bacillus subtilis.
AB  - Cytochrome aa3-600 is a terminal oxidase in the electron transport pathway that
      contributes to the electrochemical membrane potential by actively pumping
      protons. A notable feature of this enzyme complex is that it uses menaquinol as
      its electron donor instead of cytochrome c when it reduces dioxygen to water. The
      enzyme stabilizes a menasemiquinone radical (SQ) at a high affinity site that is
      important for catalysis. One of the residues that interacts with the semiquinone
      is Arg70. We have made the R70H mutant and have characterized the menasemiquinone
      radical by advanced X- and Q-band EPR. The bound SQ of the R70H mutant exhibits a
      strong isotropic hyperfine coupling (a(14)N ~ 2.0 MHz) with a hydrogen bonded
      nitrogen. This nitrogen originates from a histidine side chain, based on its
      quadrupole coupling constant, e(2)qQ/h = 1.44 MHz, typical for protonated
      imidazole nitrogens. In the wild-type cyt aa3-600, the SQ is instead hydrogen
      bonded with Nepsilon from the Arg70 side chain. Analysis of the (1)H 2D electron
      spin echo envelope modulation (ESEEM) spectra shows that the mutation also
      changes the number and strength of the hydrogen bonds between the SQ and the
      surrounding protein. Despite the alterations in the immediate environment of the
      SQ, the R70H mutant remains catalytically active. These findings are in contrast
      to the equivalent mutation in the close homologue, cytochrome bo3 ubiquinol
      oxidase from Escherichia coli, where the R71H mutation eliminates function. 

PMID- 26196463
TI  - Direct Interconversion of BINOL and H8-BINOL-Based Chiral Bronsted Acids Using
      Single-Step Red/Ox Manipulations.
AB  - A direct single-step hydrogenation of BINOL-based chiral phosphoric acids, N
      triflyl phosphoramides, and disulfonimides to the corresponding H8-BINOL Bronsted
      acids in excellent yields and chemoselectivities is described. In addition, the
      conditions for the single-step oxidation of H8-BINOL-based Bronsted acids into
      the corresponding BINOL-based acids have been identified and employed to
      accomplish these interconversions in 41-81% yield. 

PMID- 26196464
TI  - MMSET regulates expression of IRF4 in t(4;14) myeloma and its silencing
      potentiates the effect of bortezomib.
AB  - Multiple myeloma (MM) is characterized by recurrent chromosomal translocations.
      In t(4;14) MM, the MM SET domain (MMSET) protein is universally overexpressed and
      has been suggested to have an important tumorigenic role. However, the exact
      molecular targets underlying MMSET activity are not well understood. Here, we
      found in t(4;14) MM cells that MMSET knockdown decreases interferon regulatory
      factor 4 (IRF4) expression, and ectopic MMSET increases IRF4 expression,
      suggesting that MMSET is an upstream regulator of IRF4. Further analyses
      indicated an interaction between MMSET and nuclear factor-kappaB, which both bind
      to the IRF4 promoter region. A luciferase reporter assay showed that MMSET is an
      important functional element for the IRF4 promoter. MMSET knockdown induces
      apoptosis and potentiates the effects of bortezomib in vitro and in vivo.
      Importantly, we found that bortezomib could reduce expression of MMSET and IRF4.
      This might partly explain the additive effect of combining MMSET knockdown and
      bortezomib treatment. These results identify MMSET as a key regulator involved in
      the regulatory network of transcription factor IRF4, which is critical for MM
      cell survival, suggesting that the combination of MMSET inhibition and bortezomib
      is likely to improve patient outcome in MM. 

PMID- 26196465
TI  - Analysis of crash parameters and driver characteristics associated with lower
      limb injury.
AB  - This study aims to investigate changes in frequency, risk, and patterns of lower
      limb injuries due to vehicle and occupant parameters as a function of vehicle
      model year. From the National Automotive Sampling System-Crashworthiness Data
      System, 10,988 observations were sampled and analyzed, representing 4.7 million
      belted drivers involved in frontal crashes for the years 1998-2010. A logistic
      regression model was developed to understand the association of sustaining knee
      and below knee lower limb injuries of moderate or greater severity with motor
      vehicle crash characteristics such as vehicle type and model years, toepan and
      instrument panel intrusions in addition to the occupant's age, gender, height and
      weight. Toepan intrusion greater than 2cm was significantly associated with an
      increased likelihood of injury (odds ratio: 9.10, 95% confidence interval 1.82
      45.42). Females sustained a higher likelihood of distal lower limb injuries (OR:
      6.83, 1.56-29.93) as compared to males. Increased mass of the driver was also
      found to have a positive association with injury (OR: 1.04, 1.02-1.06), while age
      and height were not associated with injury likelihood. Relative to passenger
      cars, vans exhibited a protective effect against sustaining lower limb injury
      (OR: 0.24, 0.07-0.78), whereas no association was shown for light trucks (OR:
      1.31, 0.69-2.49) or SUVs (OR: 0.76, 0.28-2.02). To examine whether current crash
      testing results are representative of real-world NASS-CDS findings, data from
      frontal offset crash tests performed by the Insurance Institute for Highway
      Safety (IIHS) were examined. IIHS data indicated a decreasing trend in vehicle
      foot well and toepan intrusion, foot accelerations, tibia axial forces and tibia
      index in relation to increasing vehicle model year between the year 1995 and
      2013. Over 90% of vehicles received the highest IIHS rating, with steady
      improvement from the upper and lower tibia index, tibia axial force and the
      resultant foot acceleration considering both left and right extremities.
      Passenger cars received the highest rating followed by SUVs and light trucks,
      while vans attained the lowest rating. These results demonstrate that while there
      has been steady improvement in vehicle crash test performance, below-knee lower
      extremity injuries remain the most common AIS 2+ injury in real-world frontal
      crashes. 

PMID- 26196466
TI  - Developing crash modification functions for pedestrian signal improvement.
AB  - Pedestrian signals are viable traffic control devices that help pedestrians to
      cross safely at intersections. Although the literature is extensive when dealing
      with pedestrian signals design and operations, few studies have focused on the
      potential safety benefits of installing pedestrian signals at intersections. Most
      of these studies employed simple before-after (BA) safety evaluation techniques
      which suffer from methodological and statistical issues. Recent advances in
      safety evaluation research advocate the use of crash modification functions
      (CMFunctions) to represent the safety effectiveness of treatments. Unlike crash
      modification factors (CMFs) that are represented as single values, CMFunctions
      account for variable treatment location characteristics (heterogeneity).
      Therefore, the main objective of this study was to quantify the safety impact of
      installing pedestrian signals at signalized intersections by developing
      CMFunctions within an observational BA study. The use of observational BA
      framework to develop the CMFunctions avoids the cross-sectional approach where
      the functions are derived based on a single time period and no actual treatment
      intervention. Treatment sites heterogeneity was incorporated into CMFunctions
      using fixed-effects and random-effects regression models. In addition to
      heterogeneity, the paper also advocates the use of CMFunctions with a time
      variable to acknowledge that the safety treatment (intervention) effects do not
      occur instantaneously but are spread over future time. This is achieved using non
      linear intervention (Koyck) models, developed within a hierarchical full Bayes
      context. The results demonstrated the importance of considering treatment sites
      heterogeneity (i.e., different circulating volumes and area type among treated
      locations) and time trends when developing CMFunctions for pedestrian signal
      improvement. 

PMID- 26196467
TI  - Free Tissue Transfer in Patients with Sickle Cell Trait: Not Just a Trait.

PMID- 26196468
TI  - Mastering Cosmetic Surgery: Reflections on the Plastic and Reconstructive Surgery
      iPad Cosmetic Surgery App.

PMID- 26196469
TI  - Fighting to Reconstruct Plastic Surgery for Veterans.

PMID- 26196470
TI  - Home Improvement in Maggot Therapy: Designing a Simple, Cost-Effective, Closed
      System Habitat to Facilitate Biodebridement of Complex Distal Lower Extremity
      Wounds.

PMID- 26196471
TI  - Forms of vitality play and symbolic play during the third year of life.
AB  - This article focuses on the development of forms of vitality play, a recently
      described type of play, and links it to the development of symbolic play, one of
      the most studied types of play in developmental psychology. Two adult-infant
      dyads were videotaped longitudinally during in-house free play meetings every 15
      days during the third year of life. Convergence technique was applied in order to
      accelerate the longitudinal study. A total of 17h 48min were registered in 28
      sessions. An observational code with categories of forms of vitality play (a non
      figurative play frame in which child and adult play together with the dynamics of
      their own movements and sounds in a repetition-variation form), symbolic play,
      and categories of combined patterns of both types of play was applied. The rate
      of each play was calculated for different age periods. Forms of vitality play is
      present at a constant rate during the third year of life. Symbolic play
      flourishes during this period. Combined play patterns are not the most frequent
      but are present from the beginning to the end of the third year. We suggest that
      FoVP favours intimate and intersubjective experiences essential to the
      understanding and the development of the interpersonal world; that it can be
      thought of as a good runway for the development of symbolic play; and that it
      prepares the child to participate in the temporal arts that belong to his
      culture. 

PMID- 26196473
TI  - Screening Solid Foods Infants 1 (SSFI-1) development of a screening tool to
      detect problems in the transition from milk to solid food in infants from six to
      nine months of age.
AB  - AIM: To establish the psychometric properties of a newly developed screening tool
      Screening Solid Foods Infants 1 (SSFI-1) used by early childhood professionals,
      to detect problems in the transition from milk to solid food of smooth
      consistency in infants 6-9 months of age. METHODS: The SSFI-1 score was filled
      out by the parents of a subgroup with term infants (n=35); healthy preterm
      infants (n=26); infants with comorbidity (n=17); infants with feeding problems
      (n=13). Internal consistency, reproducibility, construct, criterion and related
      validity was evaluated. RESULTS: The preterm subgroup differed significantly in
      age when starting with fruits/vegetables and period of experience (p<0.01). The
      SSFI-1 was sufficiently reliable for the total group and term subgroup
      (alpha=0.78 and 0.76), but not for the preterm and comorbidity/feeding problem
      subgroup (alpha=0.51 and 0.69). Inter-rater reliability was high for the total
      score (n=25, ICC r=0.93), and moderate to good for individual items (weighted
      kappa range 0.55-0.95). Validity was confirmed by significantly higher scores for
      the comorbidity/feeding problem subgroups and clinically distinguishable
      subgroups (p<0.05) and area under the curve values>0.78. The initial 10-item
      screening tool was modified to a seven item screening tool. A SSFI-1 score of 4,
      +2 SD of the term subgroup, had 76.9% sensitivity and 82.1% specificity, for
      detecting the presence of a feeding problem. CONCLUSION: The seven-item screening
      tool Screening Solid Foods 1 may be used as a screening tool for term infants.
      Further testing of the SSFI-1 in new infants is needed, to confirm reliability
      and validity both for term, preterm and (risk for) feeding problem infants.

PMID- 26196472
TI  - Correlation between maternal and infant cortisol varies by breastfeeding status.
AB  - OBJECTIVE: The objective of this study was to examine associations of mother and
      infant salivary cortisol, measured three times over the course of a day, and
      assess whether these varied by breastfeeding status. METHODS: We conducted a
      cross-sectional study of 54 mothers and their infants aged 4-11 months. Mothers
      collected their own saliva and that of their infants upon awakening, 30min after
      waking and at bedtime. Breastfeeding status was reported by mothers and cortisol
      level was measured in saliva in MUg/dl using standard techniques. We used
      generalized linear models to evaluate relationships between maternal and infant
      cortisol levels, and assessed whether the relationship differed by breastfeeding
      status: formula only compared to partial and full breastfeeding, adjusting for
      infant sex, race, age, maternal education, and family income. RESULTS: Thirty
      four infants received formula only and 20 were either partially or fully
      breastfed. Breastfeeding was associated with higher household income, higher
      maternal education, and white race. Cortisol levels were higher among breastfed
      infants at all three time points. After adjustment, maternal cortisol levels were
      related with infant cortisol at bedtime only (regression estimate 0.06; 95% CI:
      0.10, 1.1; p=0.02). The adjusted association between bedtime maternal and infant
      cortisol was stronger among breastfeeding dyads than among formula-feeding dyads
      (regression estimate 1.0; 95% CI: 0.1, 2.0; p=0.04 vs. 0.6; CI: -0.1, 1.3;
      p=0.10). In addition, we assessed the influence of maternal education and
      household income in our adjusted model; income strengthened the observed
      association, whereas maternal education did not change the estimate. CONCLUSIONS:
      Breastfeeding mothers and infants had significant correlations for cortisol at
      bedtime, while formula-feeding dyads did not. These data suggest that several
      factors may contribute to cortisol synchrony observed in mother/infant dyads,
      including the transfer of cortisol in human milk, physical interaction such as
      skin-to-skin contact, and shared environment. In addition, our findings support
      household income as a possible contributor.

PMID- 26196474
TI  - Cough and Throat Clearing: Atypical GERD Symptoms or Not GERD at All?
AB  - GOALS: To investigate the frequency of throat clearing (TC) and cough and how
      often each is associated with a positive symptom index (SI) for reflux.
      BACKGROUND: Many patients referred to our esophageal laboratory for
      gastroesophageal reflux disease (GERD) evaluation have "atypical" or
      "extraesophageal" symptoms. STUDY: We reviewed ambulatory impedance-pH studies of
      267 patients referred for evaluation of possible GERD symptoms from January 2012
      to December 2013 to evaluate the frequency of cough, TC, and their association
      with an abnormal number of reflux episodes. Patients with <3 symptom events/24
      hours were excluded. Additional analysis was done for those with >=24 (excessive)
      symptoms of TC or cough/24 hours. Eighty percent of patients were tested on
      proton pump inhibitor therapy. SI for either or both symptoms was calculated.
      RESULTS: A total of 112 of 267 patients (42%) reported both TC and cough on study
      day, 76/267 (28%) cough without TC and 79/267 (30%) TC without cough. Only 9/112
      (8%) had a positive SI, versus 20/76 (26%) and 17/79 (22%) for cough (P=0.0006)
      and TC (P=0.007), respectively.A total of 136 of 267 patients (51%) reported 3 to
      23 TC events/24 hours; 27/136 (20%) had a positive SI. Fifty-five of 267 (27%)
      had "excessive" TC. Only 7/55 (13%) had a positive SI (P=0.24).A total of 142 of
      267 patients (53%) reported 3 to 23 cough events/24 hours; 43/142 (30%) had a
      positive SI. Forty-six of 267 (17%) had "excessive" cough. Only 6/46 (13%) had a
      positive SI (P=0.02).Analyses based on ON/OFF therapy, also showed same low rate
      of positive test and significantly higher number of reflux episodes in those with
      positive SI. CONCLUSIONS: Although cough and TC are often considered possible
      GERD symptoms, there is a low probability of objective association. This is even
      less likely if both symptoms are present. Those patients who reported "excessive"
      cough are less likely to have a positive SI.

PMID- 26196475
TI  - Patients With Inflammatory Bowel Disease Are Unaware of the Impact of Smoking on
      Their Disease.
AB  - BACKGOUND: Tobacco is one of the most significant risk factors for inflammatory
      bowel disease (IBD). GOALS: The main objective was to assess the knowledge of
      patients with IBD regarding the effects of tobacco on their disease. Secondary
      objectives were to determine the source of their knowledge, the influence of
      their knowledge on their intent to quit smoking, and the association between
      patients' characteristics and their knowledge. STUDY: Patients with IBD completed
      a self-administered questionnaire on demographic data, severity of disease, and
      effects of tobacco on their disease. RESULTS: In total 259 patients [182 with
      Crohn's disease, 77 with ulcerative colitis (UC)] participated. The prevalence of
      current smokers, exsmokers, and nonsmokers was 19.6%, 40.2%, and 40.2%,
      respectively. Patients with Crohn's disease were more aware of the effects of
      tobacco on their disease compared with those with UC (57.7% vs. 13.0%, P<0.0001).
      In informed patients, the main source of information was the gastroenterologist
      (56.9%). The intent to quit smoking was superior in informed patients compared
      with those uninformed (78.6% vs. 47.8%, P=0.046). Older patients (odds
      ratio=0.97, P=0.01) and patients with UC (odds ratio=0.11, P<0.0001) were less
      likely to be informed. CONCLUSIONS: Only half of patients with IBD are aware of
      the risks of smoking associated with their disease, whereas their intent to quit
      smoking is directly related to their awareness. In the scope of IBD's treatment,
      management of smoking cessation should be undertaken in all smokers.

PMID- 26196476
TI  - The pre-interventional psychiatric history - an underestimated confounder in
      benign intracranial lesions studies.
AB  - OBJECTIVES: The current study was designed to analyze the influence of a positive
      pre-interventional psychiatric history on the quality of life (QOL) after
      successful treatment of benign intracranial extra-cerebral lesions. METHODS:
      Patients treated due to meningioma WHO I or unruptured intracranial aneurysms in
      two German neurosurgical centers between 2007 and 2013 were screened for
      exclusion criteria including malignant/chronic diseases, recurrence of the
      tumor/aneurysm and neurological deficits among others. 131 patients who met the
      criteria of an objectively unaffected health status were included. The pre
      interventional psychiatric histories and the rates of post-interventional
      headaches, sleeping disorders, symptoms of chronic fatigue syndrome (CFS), post
      traumatic stress disorder (PTSD) and QOL were determined by questionnaires which
      were mailed to the patients. RESULTS: 103 patients returned the questionnaires.
      Despite the objectively unaffected health status, the patients with a positive
      pre-interventional psychiatric history demonstrated a post-interventionally
      significantly lower QOL (p=0.002), a significantly higher Pittsburgh Sleep
      Quality Index sum score (p=0.009), as well as significantly higher rates of
      symptoms of a chronic fatigue syndrome (p=0.003) and PTSD (p=0.024), compared to
      the patient collective with a negative pre-interventional psychiatric status.
      CONCLUSION: The results of the current study demonstrate the importance of taking
      the pre-interventional psychiatric history as a significant and independent
      confounder into consideration when evaluating the outcome after treatment of
      benign intracranial extra-cerebral lesions. A pre-interventional psychiatric
      screening and an early psychological intervention might help to improve the
      overall outcome after successful treatment of such lesions.

PMID- 26196477
TI  - Long-term follow-up study of 35 cases after endovascular treatment for
      vertebrobasilar dissecting aneurysms.
AB  - OBJECTIVE: Vertebrobasilar dissecting aneurysm (VBDA) management is challenging
      despite the availability of multiple treatment strategies. We reviewed our
      experiences using endovascular treatment for VBDA patients to assess the efficacy
      and safety of several VBDA treatment strategies. METHODS: Assisted by intra
      arterial digital subtraction angiography, 35 patients in our hospital were
      treated using various VBDA treatment strategies, including stent-assisted coil
      embolization (20 patients), placement of single or multiple overlapping stents (5
      patients) or coil embolization combined with proximal coil trapping of the
      dissected segment of the parent artery (CE+PT; 10 patients). We retrospectively
      reviewed the perioperative records of all 35 patients and the post-procedure
      angiographic and clinical outcomes of 31 available patients. RESULTS: Of the 25
      cases with ruptured VBDAs, 14 underwent stent-assisted coil embolization, 2
      underwent multiple overlapping stent placement and 9 underwent CE+PT.
      Perioperative complications occurred in four cases (16.0%), including one
      aneurysm rupture and one parent artery thrombosis during the procedure and two
      incidences of brainstem ischemia after the procedure. Clinical outcome
      evaluations were performed using the Modified Rankin Scale and resulted in the
      following scores: 0-2 for 22 patients (22/25, 88.0%), 5 for one patient (1/25,
      4.0%) and 6 for two patients (2/25, 8.0%). No cerebral bleeding events or deaths
      occurred during the follow-up period. Of the 10 cases with unruptured VBDAs, six
      underwent stent-assisted coil embolization, three underwent single or multiple
      overlapping stent placement and one patient underwent CE+PT. All 10 of the
      patients with unruptured VBDAs had favorable clinical and radiologic outcomes
      without procedure-related complications. CONCLUSIONS: For patients with ruptured
      VBDAs, the complication rate associated with endovascular treatment is
      acceptable. CE+PT is better than stent coiling in preventing aneurysmal
      rerupture, but is associated with a high incidence of ischemic stroke. For
      unruptured VBDAs, endovascular treatment is associated with good clinical outcome
      without perioperative complications, including rerupture and ischemic stroke.
      However, the high postoperative recurrent aneurysm risk suggests the necessity of
      long-term angiographic follow-up monitoring of VBDA patients who undergo
      endovascular treatments.

PMID- 26196478
TI  - PROSAIKA: a prospective multicenter registry with the first programmable
      gravitational device for hydrocephalus shunting.
AB  - OBJECTIVE: Cerebrospinal fluid (CSF) overdrainage is a major problem in shunt
      therapy for hydrocephalus. The adjustable gravitational valve proSA allows for
      the first time a targeted compensation for overdrainage in the upright position
      without interfering with the differential pressure valve. To evaluate benefit,
      safety and reliability, the multicenter prospective registry PROSAIKA was
      conducted in 10 German neurosurgical centers. METHODS: Between March 2009 and
      July 2010, 120 hydrocephalic patients undergoing first time shunt implantation or
      shunt revision using proSA entered the study. 93 patients completed the 12 months
      follow-up. RESULTS: Hydrocephalus symptoms were improved in 86%, unchanged in 9%
      and deteriorated in 3%. In 51%, the proSA opening pressure was readjusted one or
      several times to treat suspected suboptimal shunt function, this resulted in
      clinical improvement in 55%, no change in 25%, and deterioration in 20% of these
      patients. The 1 year censored proSA shunt survival rate was 89%. Device related
      shunt failure was seen in two cases. CONCLUSIONS: This is the first clinical
      report on the implantation of the adjustable gravitational valve proSA with a
      follow-up of 12 months in a substantial number of patients. Irrespective of
      different hydrocephalus etiologies and indications for shunt surgery, the overall
      results after 12 months were very satisfying. The high frequency of valve
      readjustments underlines the fact that preoperative selection of the appropriate
      valve opening pressure is difficult. The low number of revisions and
      complications compared to other valves proves that proSA implantation adds no
      further risk; this valve is reliable, helpful and safe.

PMID- 26196479
TI  - Chronically Alternating Light Cycles Increase Breast Cancer Risk in Mice.
AB  - Although epidemiological studies in shift workers and flight attendants have
      associated chronic circadian rhythm disturbance (CRD) with increased breast
      cancer risk, causal evidence for this association is lacking. Several scenarios
      have been proposed to contribute to the shift work-cancer connection: (1)
      internal desynchronization, (2) light at night (resulting in melatonin
      suppression), (3) sleep disruption, (4) lifestyle disturbances, and (5) decreased
      vitamin D levels due to lack of sunlight. The confounders inherent in human field
      studies are less problematic in animal studies, which are therefore a good
      approach to assess the causal relation between circadian disturbance and cancer.
      However, the experimental conditions of many of these animal studies were far
      from the reality of human shift workers. For example, some involved xenografts
      (addressing tumor growth rather than cancer initiation and/or progression),
      chemically induced tumor models, or continuous bright light exposure, which can
      lead to suppression of circadian rhythmicity. Here, we have exposed breast cancer
      prone p53(R270H/+)WAPCre conditional mutant mice (in a FVB genetic background) to
      chronic CRD by subjecting them to a weekly alternating light-dark (LD) cycle
      throughout their life. Animals exposed to the weekly LD inversions showed a
      decrease in tumor suppression. In addition, these animals showed an increase in
      body weight. Importantly, this study provides the first experimental proof that
      CRD increases breast cancer development. Finally, our data suggest internal
      desynchronization and sleep disturbance as mechanisms linking shift work with
      cancer development and obesity.

PMID- 26196480
TI  - Egernia lizards.
AB  - While et al's quick guide to Egernia lizards, a group of social lizards from
      Austalasia. 

PMID- 26196481
TI  - Competition drives sophisticated hunting skills of archerfish in the wild.
AB  - Several animals are renowned for their cognitive skills, such as tool use,
      metacognition or social learning. However, it remains puzzling why some species
      excel whereas others - sometimes even closely related ones - do not. Archerfish
      show a remarkable assembly of skills in the context of their unique hunting
      behavior in which they down aerial prey with shots of water. Hoping to find
      ecological factors behind these skills, we have over the past years regularly
      traveled to archerfish mangrove habitats in Thailand (Figure 1A). One of our most
      consistent findings was the presence of other surface-feeding fish, particularly
      the similar-sized halfbeak Zenarchopterus buffonis, wherever we spotted groups of
      archerfish (Figure 1A; Supplemental movie S1). We describe here that
      Zenarchopterus is superbly equipped with water-wave detectors, rapidly detects
      the impact of prey even in the dark, is active at all times, is usually more
      numerous than archerfish and supplements its capabilities with visual skills.
      Without sophisticated additions to their hunting technique archerfish would thus
      lose most of their downed prey to halfbeaks. We suggest that the evolution of
      several skills of archerfish may have thus been influenced not only by
      intraspecific competition [5] but also by competition with other surface-feeding
      fish species.

PMID- 26196482
TI  - The gambler's fallacy in penalty shootouts.
AB  - A well-known bias in subjective perceptions of chance is the gambler's fallacy:
      people typically believe that a streak generated by a series of independent
      random draws, such as a coin toss, becomes increasingly more likely to break when
      the streak becomes longer. In a fascinating study, Misirlisoy and Haggard
      analysed sequential behavior of kickers and goalkeepers in penalty shootouts.
      They report that goalkeepers are prone to the gambler's fallacy: after a series
      of three kicks in the same direction, goalkeepers are more likely to dive in the
      opposite direction at the next kick. Here we argue, first, that a binomial test
      is more appropriate for testing gambler's fallacy than the tests employed by
      Misirlisoy and Haggard, and second, that penalty shootouts may not be well-suited
      to analyze the gambler's fallacy. Using a binomial test, we neither find
      statistically significant evidence for gambler's fallacy in Misirlisoy and
      Haggard's original data, nor in extended data, nor in data from an idealised
      laboratory experiment that we ran to address the second point. In line with
      Misirlisoy and Haggard's original result, we do, however, find evidence for a
      systematic pattern of goalkeeper's behavior that kickers could exploit.

PMID- 26196483
TI  - Reply to Braun and Schmidt.
AB  - We welcome and appreciate the comment by Braun and Schmidt on our recent
      correspondence about the gambler's fallacy in goalkeeper behaviour during penalty
      shoot-outs. Braun and Schmidt assert that the binomial is more appropriate for
      analysing the data than our resampling approach. Their analyses appear to assume
      that dive direction is binomially distributed with a probability of 0.5. In fact,
      there are several biases in goalkeeper behaviour. First, we showed that kickers
      have a slight bias to kick to the goalkeeper's right, and that goalkeepers also
      have a slight bias to dive rightwards. This bias did not cross the conventional
      significance threshold in our data, but it still cannot be ignored when modelling
      sequences of actions. Repeated independent sampling from any distribution
      produces a sequential pattern that depends on the bias. The binomial distribution
      used to test hypotheses about sequential dependence should, therefore, have the
      same biases as the actual sample.

PMID- 26196484
TI  - Social Behavior: A Penny for Your Shocks.
AB  - Antisocial behavior is an enormously costly social problem, but its origins are
      poorly understood. A new study shows that prosocial and antisocial behaviors
      arise from individual differences in how we represent the value of others' pain
      relative to our own potential gain, rather than from variability in the capacity
      for effortful inhibitory control. 

PMID- 26196485
TI  - Chromosome Segregation: A Spatial Code to Correct Kinetochore-Microtubule
      Attachments.
AB  - Erroneous kinetochore-microtubule interactions must be detected and corrected
      before a cell enters anaphase to prevent chromosome mis-segregation. Two new
      studies describe an Aurora A-mediated error correction mechanism based on the
      spatial position of a chromosome within the mitotic spindle. 

PMID- 26196486
TI  - Plant Immune Responses: Aphids Strike Back.
AB  - To survive and complete their life cycle, herbivorous insects face the difficult
      challenge of coping with the arsenal of plant defences. A new study reports that
      aphids secrete evolutionarily conserved cytokines in their saliva to suppress
      host immune responses. 

PMID- 26196487
TI  - Drosophila Neurobiology: No Escape from 'Big Data' Science.
AB  - Combining a variety of large-scale, data-intensive techniques, a recent study has
      unraveled the neural pathways involved in Drosophila larval escape from a
      parasitoid wasp invasion. 

PMID- 26196488
TI  - Sensory Biology: Acoustic Reflectors Attract Bats to Roost in Pitcher Plants.
AB  - A new study shows that a carnivorous plant attracts bats by possessing modified
      pitfall taps that increase the reflectivity of echolocation calls. Bats benefit
      by finding roosting sites, and the plants gain by receiving nitrogen from guano. 

PMID- 26196489
TI  - Gut Microbiome: Westernization and the Disappearance of Intestinal Diversity.
AB  - The environment shapes our intestinal microbiome. By contrasting the gut
      microbiomes of African hunter-gatherer and European subjects, a new study reveals
      that urbanization is associated with a loss of microbial organisms and genes.
      What will be the consequences of the lost biodiversity in the sanitized, western
      diet world? 

PMID- 26196490
TI  - Evolution: Sex Limits Adaptation.
AB  - Evolution is affected by survival of individuals and by mate choice, but how
      sexual selection affects adaptation remains unclear. A new study finds that
      sexual selection can limit adaptation by causing male-induced harm to females and
      thus opposing natural selection. 

PMID- 26196491
TI  - Palaeontology: Clearing the Heads of Cambrian Arthropods.
AB  - Understanding the identity of segments and the evolution of their appendages is a
      prime concern of arthropod evolution studies. This has been challenging for long
      extinct stem-groups. Now, Cambrian fossils offer insights that will help further
      evolutionary considerations. 

PMID- 26196492
TI  - Ecology: Tribal Warfare Maintains Microbial Diversity.
AB  - When two tribes of Myxococcus bacteria attack each other, the most numerous
      usually wins. Established colonies can therefore resist invaders by outnumbering
      them. This shows how positive frequency dependence can maintain diversity across
      spatially structured environments. 

PMID- 26196493
TI  - The Human Face as a Dynamic Tool for Social Communication.
AB  - As a highly social species, humans frequently exchange social information to
      support almost all facets of life. One of the richest and most powerful tools in
      social communication is the face, from which observers can quickly and easily
      make a number of inferences - about identity, gender, sex, age, race, ethnicity,
      sexual orientation, physical health, attractiveness, emotional state, personality
      traits, pain or physical pleasure, deception, and even social status. With the
      advent of the digital economy, increasing globalization and cultural integration,
      understanding precisely which face information supports social communication and
      which produces misunderstanding is central to the evolving needs of modern
      society (for example, in the design of socially interactive digital avatars and
      companion robots). Doing so is challenging, however, because the face can be
      thought of as comprising a high-dimensional, dynamic information space, and this
      impacts cognitive science and neuroimaging, and their broader applications in the
      digital economy. New opportunities to address this challenge are arising from the
      development of new methods and technologies, coupled with the emergence of a
      modern scientific culture that embraces cross-disciplinary approaches. Here, we
      briefly review one such approach that combines state-of-the-art computer
      graphics, psychophysics and vision science, cultural psychology and social
      cognition, and highlight the main knowledge advances it has generated. In the
      light of current developments, we provide a vision of the future directions in
      the field of human facial communication within and across cultures. 

PMID- 26196494
TI  - MOSAIC--A Modular Approach to Data Management in Epidemiological Studies.
AB  - INTRODUCTION: In the context of an increasing number of multi-centric studies
      providing data from different sites and sources the necessity for central data
      management (CDM) becomes undeniable. This is exacerbated by a multiplicity of
      featured data types, formats and interfaces. In relation to methodological
      medical research the definition of central data management needs to be broadened
      beyond the simple storage and archiving of research data. OBJECTIVES: This paper
      highlights typical requirements of CDM for cohort studies and registries and
      illustrates how orientation for CDM can be provided by addressing selected data
      management challenges. METHODS: Therefore in the first part of this paper a short
      review summarises technical, organisational and legal challenges for CDM in
      cohort studies and registries. A deduced set of typical requirements of CDM in
      epidemiological research follows. RESULTS: In the second part the MOSAIC project
      is introduced (a modular systematic approach to implement CDM). The modular
      nature of MOSAIC contributes to manage both technical and organisational
      challenges efficiently by providing practical tools. A short presentation of a
      first set of tools, aiming for selected CDM requirements in cohort studies and
      registries, comprises a template for comprehensive documentation of data
      protection measures, an interactive reference portal for gaining insights and
      sharing experiences, supplemented by modular software tools for generation and
      management of generic pseudonyms, for participant management and for
      sophisticated consent management. CONCLUSIONS: Altogether, work within MOSAIC
      addresses existing challenges in epidemiological research in the context of CDM
      and facilitates the standardized collection of data with pre-programmed modules
      and provided document templates. The necessary effort for in-house programming is
      reduced, which accelerates the start of data collection.

PMID- 26196495
TI  - Not All Hip Dysplasias are the Same: Preoperative CT Version Study and the Need
      for Reverse Bernese Periacetabular Osteotomy.
AB  - BACKGROUND: Dysplastic hip may present with acetabular retroversion with or
      without femoral retroversion. This retroversion, if not accounted for when
      performing a periacetabular osteotomy (PAO), will lead to anterior hip pain and
      early osteoarthritis. A reverse PAO involves anteverting the acetabulum while
      still obtaining lateral coverage. The purpose of this study was to investigate
      the relationship between rotational malalignment of acetabulum and femur on 2
      dimensional computed tomographic (CT) scans of hips that underwent Bernese PAO
      and its role in the surgical decision making. METHODS: This retrospective, case
      control study examined and compared preoperative 2-dimensional CT scans of hips
      that underwent reverse PAO to the hips that underwent traditional PAO. RESULTS:
      Twelve hips underwent reverse PAO from 2005 to 2010. Twelve hips were randomly
      selected from a cohort of 52 hips that underwent traditional PAO during same time
      period. Hips that underwent reverse PAO showed crossover sign on preoperative
      radiographs, but not on postoperative radiographs. Crossover sign was negative
      preoperatively and postoperatively on hips that underwent traditional PAO. The 2
      groups were similar in regards to preoperative lateral center-edge angle,
      acetabular index, and anterior center-edge angle on plain radiographs and showed
      significant improvement after surgery.On preoperative CT scans both acetabulae
      and femurs were retroverted in reverse PAO group. Comparison of the 2 groups
      demonstrated that acetabular version (16.5+/-4.9 degrees vs. 25.3+/-5.6 degrees,
      P=0.001), femoral version (12.8+/-10.4 degrees vs. 31.9+/-8 degrees, P<0.001),
      and McKibbins Instability Index (29.3+/-11.9 degrees vs. 57.1+/-9.8 degrees,
      P<0.001) were significantly lower for the reverse PAO than the traditional PAO
      group. Anterior Acetabular Sector Angle (determines anterior coverage) was
      significantly higher in reverse PAO group, 53.1+/-13.7 degrees versus 39.7+/-10.4
      degrees (P=0.013). CONCLUSIONS: Retroverted acetabulae seem to be associated with
      reduced femoral version. Given that retroverted acetabulum and retroverted femur
      have additive effect and increase chances of anterior hip pain, preoperative
      identification of correct acetabular, and femoral version by CT scan or MRI is
      necessary to determine which hip need reverse PAO as opposed to traditional PAO.
      LEVEL OF EVIDENCE: Level III-Therapeutic.

PMID- 26196496
TI  - Surgical Decompression of Exertional Compartment Syndrome of the Forearm in
      Professional Motorcycling Racers: Comparative Long-term Results of Wide-Open
      Versus Mini-Open Fasciotomy.
AB  - OBJECTIVE: To compare the long-term results of 2 surgical techniques for forearm
      chronic exertional compartment syndrome (CECS) in professional motorcycling
      racers and to study a new diagnostic variable for CECS, TRest. DESIGN:
      Retrospective case series. LEVEL OF EVIDENCE: 4. SETTING: University Hospital.
      PARTICIPANTS: Thirty-four patients identified from a surgical database who had
      been operated on for upper-limb CECS. INTERVENTIONS: The purpose of the study was
      to report and compare the long-term results of 2 surgical techniques using
      fasciotomies [wide-open fasciotomy (WOF) versus mini-open fasciotomy (MOF)] for
      forearm CECS in professional motorcycling racers. MAIN OUTCOME MEASURES:  PATIENT
      CHARACTERISTICS: Pain [visual analog scale (100-point scale)] and functional
      scores (Quick-DASH) at 3 months after surgery and at regular intervals during
      clinical visits. Surgical complications: Level of satisfaction with the outcome.
      Time to return to full activity after surgery. RESULTS: Thirty-four racers, 22
      with bilateral involvement (n = 56), were diagnosed with CECS and were treated
      either with WOF (n = 24) or MOF (n = 32) depending on the surgeon's indication.
      Mini-open fasciotomy was usually selected in cases who need a faster recovery
      because of competition schedule. Visual analog scale and Quick-DASH improved 63
      and 73 points, respectively (P < 0.001) with no significant difference between
      both surgical methods (P = 0.512). Both WOF and MOF were equally effective.
      Ninety-four percent of the patients were satisfied after 45.35 +/- 12 months of
      follow-up, with no significant difference between surgical groups (P = 0.642).
      The time to return to full activity was 2.7 +/- 1 week, also with no significant
      difference (P = 0.544). The time between when the stress testing was halted for
      pain and the return to baseline pressure (TRest) was superior to 15 minutes
      (defined as the mean minus 2 SDs) in 100% patients. CONCLUSIONS: Surgical open or
      mini-invasive fasciotomy is equally successful in motorcycling racers with
      forearm CECS. Although the sensitivity of TRest is quite high in our series,
      further studies are still needed to validate its diagnostic value. CLINICAL
      RELEVANCE: Surgical open or mini-invasive fasciotomy is equally successful in
      motorcycling racers with forearm CECS.

PMID- 26196497
TI  - Flavonoids and Methoxy-galloylquinic Acid Derivatives from the Leaf Extract of
      Copaifera langsdorffii Desf.
AB  - Despite reports on the pharmacological potential of Copaifera langsdorffii Desf.
      (Leguminosae-Caesalpinioideae) leaf extract, little is known about its chemical
      composition. In this work, a phytochemical study from the C. langsdorffii
      ethanol/H2O 7:3 (v/v) extract was undertaken. Separation was performed by high
      speed counter-current (HSCCC) and Sephadex LH-20 column chromatographies,
      followed by preparative HPLC. The EtOAc- and H2O-soluble fractions of the extract
      furnished the flavonoids quercitrin (1) and afzelin (2) and 3-O-(3-O-methyl
      galloyl)quinic acid (3), respectively. The H2O-soluble fraction furnished 3,4-di
      O-(3-O-methyl-galloyl)quinic acid (4), 3,5-di-O-(galloyl)-4-O-(3-O-methyl
      galloyl)quinic acid (5), and 3,5-di-O-(3-O-methyl-galloyl)-4-O-(galloyl)quinic
      acid (6). Their chemical structures were elucidated by NMR means. 

PMID- 26196498
TI  - Isotope Fractionation Associated with the Photochemical Dechlorination of
      Chloroanilines.
AB  - Isotope fractionation associated with the photochemical transformation of organic
      contaminants is not well understood and can arise not only from bond cleavage
      reactions but also from photophysical processes. In this work, we investigated
      the photolytic dechlorination of 2-Cl- and 3-Cl-aniline to aminophenols to obtain
      insights into the impact of the substituent position on the apparent (13)C and
      (15)N kinetic isotope effects (AKIEs). Laboratory experiments were performed in
      aerated aqueous solutions at an irradiation wavelength of 254 nm over the pH
      range 2.0 to 7.0 in the absence and presence of Cs(+) used as an excited singlet
      state quencher. Photolysis of 2-Cl-anilinium cations exhibits normal C and
      inverse N isotope fractionation, while neutral 2-Cl-aniline species shows inverse
      C and normal N isotope fractionation. In contrast, the photolysis of 3-Cl-aniline
      was almost insensitive to C isotope composition and the moderate N isotope
      fractionation points to rate-limiting photophysical processes. (13)C- and (15)N
      AKIE-values of 2-Cl-aniline decreased in the presence of Cs(+), whereas those for
      3-Cl-aniline were not systematically affected by Cs(+). Our current and previous
      work illustrates that photolytic dechlorinations of 2-Cl-, 3-Cl-, and 4-Cl
      aniline isomers are each accompanied by distinctly different and highly variable
      C and N isotope fractionation due to spin selective isotope effects.

PMID- 26196499
TI  - Pulse-driven micro gas sensor fitted with clustered Pd/SnO2 nanoparticles.
AB  - Real-time monitoring of specific gas concentrations with a compact and portable
      gas sensing device is required to sense potential health risk and danger from
      toxic gases. For such purposes, we developed an ultrasmall gas sensor device,
      where a micro sensing film was deposited on a micro heater integrated with
      electrodes fabricated by the microelectromechanical system (MEMS) technology. The
      developed device was operated in a pulse-heating mode to significantly reduce the
      heater power consumption and make the device battery-driven and portable. Using
      clustered Pd/SnO2 nanoparticles, we succeeded in introducing mesopores ranging
      from 10 to 30 nm in the micro gas sensing film (area: phi 150 MUm) to detect
      large volatile organic compounds (VOCs). The micro sensor showed quick, stable,
      and high sensor responses to toluene at ppm (parts per million) concentrations at
      300  degrees C even by operating the micro heater in a pulse-heating mode where
      switch-on and -off cycles were repeated at one-second intervals. The high
      performance of the micro sensor should result from the creation of efficient
      diffusion paths decorated with Pd sensitizers by using the clustered Pd/SnO2
      nanoparticles. Hence we demonstrate that our pulse-driven micro sensor using
      nanostructured oxide materials holds promise as a battery-operable, portable gas
      sensing device. 

PMID- 26196500
TI  - Structural characterization by transmission electron microscopy and
      immunoreactivity of recombinant Hendra virus nucleocapsid protein expressed and
      purified from Escherichia coli.
AB  - Hendra virus (family Paramyxoviridae) is a negative sense single-stranded RNA
      virus (NSRV) which has been found to cause disease in humans, horses, and
      experimentally in other animals, e.g. pigs and cats. Pteropid bats commonly known
      as flying foxes have been identified as the natural host reservoir. The Hendra
      virus nucleocapsid protein (HeV N) represents the most abundant viral protein
      produced by the host cell, and is highly immunogenic with naturally infected
      humans and horses producing specific antibodies towards this protein. The purpose
      of this study was to express and purify soluble, functionally active recombinant
      HeV N, suitable for use as an immunodiagnostic reagent to detect antibodies
      against HeV. We expressed both full-length HeV N, (HeV NFL), and a C-terminal
      truncated form, (HeV NCORE), using a bacterial heterologous expression system.
      Both HeV N constructs were engineered with an N-terminal Hisx6 tag, and purified
      using a combination of immobilized metal affinity chromatography (IMAC) and size
      exclusion chromatography (SEC). Purified recombinant HeV N proteins self
      assembled into soluble higher order oligomers as determined by SEC and negative
      stain transmission electron microscopy. Both HeV N proteins were highly immuno
      reactive with sera from animals and humans infected with either HeV or the
      closely related Nipah virus (NiV), but displayed no immuno-reactivity towards
      sera from animals infected with a non-pathogenic paramyxovirus (CedPV), or
      animals receiving Equivac(r) (HeV G glycoprotein subunit vaccine), using a
      Luminex-based multiplexed microsphere assay. 

PMID- 26196501
TI  - Expression and purification of Canis interferon alpha in Escherichia coli using
      different tags.
AB  - The potent and broad activity of Canis interferon alpha (CaIFNalpha) makes it an
      attractive candidate for the treatment of many viral diseases of dogs. Here, we
      fused CaIFNalpha to three different protein tags: thioredoxin (Trx), glutathione
      S-transferase (GST), and NusA (Nus), to facilitate its expression and
      purification in Escherichia coli. The Trx-CaIFNalpha and GST-CaIFNalpha fusion
      proteins formed inclusion bodies, while the Nus-CaIFNalpha protein was soluble
      when expressed at low temperatures. Trx-CaIFNalpha was purified from inclusion
      bodies and refolded, while Nus-CaIFNalpha was purified under native conditions.
      The purity of Trx-CaIFNalpha and Nus-CaIFNalpha was greater than 90%, and their
      yields were 74.8% and 6.5%, respectively. Both Trx-CaIFNalpha and Nus-CaIFNalpha
      had antiviral activity in vitro. Their anti-viral activity was 1.09+/-0.47*10(14)
      and 2.25+/-0.87*10(12) U/mol, respectively, on Madin-Darby canine kidney cells.
      Both purification methods had advantages and disadvantages. A greater amount of
      Trx-CaIFNalpha was obtained, but refolding was required to obtain active protein.
      In contrast, soluble Nus-CaIFNalpha did not require refolding, which saved time
      and materials. However, Nus-CaIFNalpha, which contained a larger tag, had lower
      activity than Trx-CaIFNalpha. In general, we provided two protocols to obtain
      large amounts of CaIFNalpha with high antiviral activity. These protocols may
      promote the clinical development of CaIFNalpha in treating viral diseases in dog.

PMID- 26196502
TI  - Daclatasvir plus Sofosbuvir for HCV in Patients Coinfected with HIV-1.
AB  - BACKGROUND: The combination of daclatasvir, a hepatitis C virus (HCV) NS5A
      inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with
      HCV monoinfection. Data are lacking on the efficacy and safety of this
      combination in patients coinfected with human immunodeficiency virus type 1 (HIV
      1). METHODS: This was an open-label study involving 151 patients who had not
      received HCV treatment and 52 previously treated patients, all of whom were
      coinfected with HIV-1. Previously untreated patients were randomly assigned in a
      2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose
      of 60 mg daily (with dose adjustment for concomitant antiretroviral medications)
      plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to
      undergo 12 weeks of therapy at the same doses. The primary end point was a
      sustained virologic response at week 12 after the end of therapy among previously
      untreated patients with HCV genotype 1 who were treated for 12 weeks. RESULTS:
      Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had
      compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients
      with genotype 1, a sustained virologic response was reported in 96.4% (95%
      confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in
      75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously
      untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12
      weeks among previously treated patients. Rates of sustained virologic response
      across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to
      86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse
      events were fatigue, nausea, and headache. There were no study-drug
      discontinuations because of adverse events. HIV-1 suppression was not
      compromised. CONCLUSIONS: Among previously untreated HIV-HCV coinfected patients
      receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained
      virologic response across all genotypes was 97.0% after 12 weeks of treatment and
      76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov
      number, NCT02032888.).

PMID- 26196504
TI  - Multidrug-Resistant Tuberculosis in Patients for Whom First-Line Treatment
      Failed, Mongolia, 2010-2011.
AB  - In Ulaanbaatar, Mongolia, multidrug-resistant tuberculosis (MDR TB) was diagnosed
      for more than a third of new sputum smear-positive tuberculosis patients for whom
      treatment had failed. This finding suggests a significant risk for community
      acquired MDR TB and a need to make rapid molecular drug susceptibility testing
      available to more people. 

PMID- 26196503
TI  - Esters of Bendamustine Are by Far More Potent Cytotoxic Agents than the Parent
      Compound against Human Sarcoma and Carcinoma Cells.
AB  - The alkylating agent bendamustine is approved for the treatment of hematopoietic
      malignancies such as non-Hodgkin lymphoma, chronic lymphocytic leukemia and
      multiple myeloma. As preliminary data on recently disclosed bendamustine esters
      suggested increased cytotoxicity, we investigated representative derivatives in
      more detail. Especially basic esters, which are positively charged under
      physiological conditions, were in the crystal violet and the MTT assay up to
      approximately 100 times more effective than bendamustine, paralleled by a higher
      fraction of early apoptotic cancer cells and increased expression of p53.
      Analytical studies performed with bendamustine and representative esters revealed
      pronounced cellular accumulation of the derivatives compared to the parent
      compound. In particular, the pyrrolidinoethyl ester showed a high enrichment in
      tumor cells and inhibition of OCT1- and OCT3-mediated transport processes,
      suggesting organic cation transporters to be involved. However, this hypothesis
      was not supported by the differential expression of OCT1 (SLC22A1) and OCT3
      (SLC22A3), comparing a panel of human cancer cells. Bendamustine esters proved to
      be considerably more potent cytotoxic agents than the parent compound against a
      broad panel of human cancer cell types, including hematologic and solid
      malignancies (e.g. malignant melanoma, colorectal carcinoma and lung cancer),
      which are resistant to bendamustine. Interestingly, spontaneously immortalized
      human keratinocytes, as a model of "normal" cells, were by far less sensitive
      than tumor cells against the most potent bendamustine esters.

PMID- 26196505
TI  - Physical Forces between Humans and How Humans Attract and Repel Each Other Based
      on Their Social Interactions in an Online World.
AB  - Physical interactions between particles are the result of the exchange of gauge
      bosons. Human interactions are mediated by the exchange of messages, goods,
      money, promises, hostilities, etc. While in the physical world interactions and
      their associated forces have immediate dynamical consequences (Newton's laws) the
      situation is not clear for human interactions. Here we quantify the relative
      acceleration between humans who interact through the exchange of messages, goods
      and hostilities in a massive multiplayer online game. For this game we have
      complete information about all interactions (exchange events) between about
      430,000 players, and about their trajectories (movements) in the metric space of
      the game universe at any point in time. We use this information to derive
      "interaction potentials" for communication, trade and attacks and show that they
      are harmonic in nature. Individuals who exchange messages and trade goods
      generally attract each other and start to separate immediately after exchange
      events end. The form of the interaction potential for attacks mirrors the usual
      "hit-and-run" tactics of aggressive players. By measuring interaction intensities
      as a function of distance, velocity and acceleration, we show that "forces"
      between players are directly related to the number of exchange events. We find an
      approximate power-law decay of the likelihood for interactions as a function of
      distance, which is in accordance with previous real world empirical work. We show
      that the obtained potentials can be understood with a simple model assuming an
      exchange-driven force in combination with a distance-dependent exchange rate.

PMID- 26196506
TI  - Intracellular pH-Triggered, Targeted Drug Delivery to Cancer Cells by
      Multifunctional Envelope-Type Mesoporous Silica Nanocontainers.
AB  - In this work, a novel type of pH-sensitive multifunctional envelope-type
      mesoporous silica nanocontainers (SBDAPF) was constructed for targeted drug
      delivery to cancer cells. Poly(N-succinimidyl acrylate) was coated on the
      mesoporous silica nanoparticles surface via an acid-labile acetal linker to
      obtain the SBA particles for pH-triggered drug release. A model drug doxorubicin
      (DOX)-loaded SBA system (SBDA) showed low premature drug release at neutral pH
      and effective stimuli-responsive release under the acidic conditions. To provide
      the colloidal stability and avoid nonspecific uptake of normal or healthy cells,
      the SBDA nanocontainers were modified with a poly(ethylene glycol) (PEG) polymer
      to form a protection layer. Furthermore, folic acid was introduced as a targeting
      component and anchored on the PEG outer layer to achieve the cancer-targeting
      ability. In vitro study demonstrated that SBDAPF could selectively adhere to the
      surface of cancer cells through the specific binding with folate receptor and be
      internalized into cells, subsequently releasing the entrapped DOX with high
      efficiency in slightly acidic intracellular microenvironment to finally kill
      cancer cells. Such a versatile drug delivery system as SBDAPF should have a
      potential application in cancer therapy. 

PMID- 26196507
TI  - Correction: A Role for MicroRNA-155 Expression in Microenvironment Associated to
      HPV-Induced Carcinogenesis in K14-HPV16 Transgenic Mice.

PMID- 26196508
TI  - Effects of Adaptation Rate and Noise Suppression on the Intelligibility of
      Compressed-Envelope Based Speech.
AB  - Temporal envelope is the primary acoustic cue used in most cochlear implant (CI)
      speech processors to elicit speech perception for patients fitted with CI
      devices. Envelope compression narrows down envelope dynamic range and accordingly
      degrades speech understanding abilities of CI users, especially under challenging
      listening conditions (e.g., in noise). A new adaptive envelope compression (AEC)
      strategy was proposed recently, which in contrast to the traditional static
      envelope compression, is effective at enhancing the modulation depth of envelope
      waveform by making best use of its dynamic range and thus improving the
      intelligibility of envelope-based speech. The present study further explored the
      effect of adaptation rate in envelope compression on the intelligibility of
      compressed-envelope based speech. Moreover, since noise reduction is another
      essential unit in modern CI systems, the compatibility of AEC and noise reduction
      was also investigated. In this study, listening experiments were carried out by
      presenting vocoded sentences to normal hearing listeners for recognition.
      Experimental results demonstrated that the adaptation rate in envelope
      compression had a notable effect on the speech intelligibility performance of the
      AEC strategy. By specifying a suitable adaptation rate, speech intelligibility
      could be enhanced significantly in noise compared to when using static envelope
      compression. Moreover, results confirmed that the AEC strategy was suitable for
      combining with noise reduction to improve the intelligibility of envelope-based
      speech in noise. 

PMID- 26196509
TI  - A Synthetic Quorum Sensing System Reveals a Potential Private Benefit for Public
      Good Production in a Biofilm.
AB  - Bacteria predominantly reside in microbial communities known as biofilms, where
      cells are encapsulated and protected by the extracellular matrix (ECM). While all
      biofilm cells benefit from the ECM, only a subgroup of cells carries the burden
      of producing this public good. This dilemma provokes the question of how these
      cells balance the cost of ECM production. Here we show that ECM producing cells
      have a higher gene expression response to quorum sensing (QS) signals, which can
      lead to a private benefit. Specifically, we constructed a synthetic quorum
      sensing system with designated "Sender" and "Receiver" cells in Bacillus
      subtilis. This synthetic QS system allowed us to uncouple and independently
      investigate ECM production and QS in both biofilms and single cells. Results
      revealed that ECM production directly enhances the response to QS signals, which
      may offset the cost of ECM production.

PMID- 26196510
TI  - Trade-Off between Growth and Carbohydrate Accumulation in Nutrient-Limited
      Arthrospira sp. PCC 8005 Studied by Integrating Transcriptomic and Proteomic
      Approaches.
AB  - Cyanobacteria have a strong potential for biofuel production due to their ability
      to accumulate large amounts of carbohydrates. Nitrogen (N) stress can be used to
      increase the content of carbohydrates in the biomass, but it is expected to
      reduce biomass productivity. To study this trade-off between carbohydrate
      accumulation and biomass productivity, we characterized the biomass productivity,
      biomass composition as well as the transcriptome and proteome of the
      cyanobacterium Arthrospira sp. PCC 8005 cultured under N-limiting and N-replete
      conditions. N limitation resulted in a large increase in the carbohydrate content
      of the biomass (from 14 to 74%) and a decrease in the protein content (from 37 to
      10%). Analyses of fatty acids indicated that no lipids were accumulated under N
      limited conditions. Nevertheless, it did not affect the biomass productivity of
      the culture up to five days after N was depleted from the culture medium.
      Transcriptomic and proteomic analysis indicated that de novo protein synthesis
      was down-regulated in the N-limited culture. Proteins were degraded and partly
      converted into carbohydrates through gluconeogenesis. Cellular N derived from
      protein degradation was recycled through the TCA and GS-GOGAT cycles. In
      addition, photosynthetic energy production and carbon fixation were both down
      regulated, while glycogen synthesis was up-regulated. Our results suggested that
      N limitation resulted in a redirection of photosynthetic energy from protein
      synthesis to glycogen synthesis. The fact that glycogen synthesis has a lower
      energy demand than protein synthesis might explain why Arthrospira is able to
      achieve a similar biomass productivity under N-limited as under N-replete
      conditions despite the fact that photosynthetic energy production was impaired by
      N limitation.

PMID- 26196511
TI  - Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine
      Model of CNS Neuroinflammation.
AB  - Gliogenesis under pathophysiological conditions is of particular clinical
      relevance since it may provide evidence for regeneration promoting cells
      recruitable for therapeutic purposes. There is evidence that neurotrophin
      receptor p75 (p75NTR)-expressing cells emerge in the lesioned CNS. However, the
      phenotype and identity of these cells, and signals triggering their in situ
      generation under normal conditions and certain pathological situations has
      remained enigmatic. In the present study, we used a spontaneous, idiopathic and
      inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration
      as a model to study the phenotype of Schwann cells and their relation to Schwann
      cell remyelination within the CNS. Furthermore, the phenotype of p75NTR
      expressing cells within the injured CNS was compared to their counter-part in
      control sciatic nerve and after peripheral nerve injury. In addition, organotypic
      slice cultures were used to further elucidate the origin of p75NTR-positive
      cells. In cerebral and cerebellar white and grey matter lesions as well as in the
      brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but
      not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-alpha. Interestingly, and
      contrary to the findings in control sciatic nerves, p75NTR-expressing cells only
      co-localized with Sox2 in degenerative neuropathy, thus suggesting that such
      cells might represent dedifferentiated Schwann cells both in the injured CNS and
      PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and
      P0-positive mature myelinating Schwann cells, was strikingly associated with the
      presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of
      dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage
      dominated inflammatory response provided an adequate environment for Schwann
      cells plasticity within the injured CNS. Furthermore, axonal damage was reduced
      in brain stem areas with p75NTR/Sox2-positive cells. This study provides novel
      insights into the involvement of Schwann cells in CNS remyelination under natural
      occurring CNS inflammation. Targeting p75NTR/Sox2-expressing Schwann cells to
      enhance their differentiation into competent remyelinating cells appears to be a
      promising therapeutic approach for inflammatory/demyelinating CNS diseases. 

PMID- 26196512
TI  - Nested PCR Biases in Interpreting Microbial Community Structure in 16S rRNA Gene
      Sequence Datasets.
AB  - BACKGROUND: Sequencing of the PCR-amplified 16S rRNA gene has become a common
      approach to microbial community investigations in the fields of human health and
      environmental sciences. This approach, however, is difficult when the amount of
      DNA is too low to be amplified by standard PCR. Nested PCR can be employed as it
      can amplify samples with DNA concentration several-fold lower than standard PCR.
      However, potential biases with nested PCRs that could affect measurement of
      community structure have received little attention. RESULTS: In this study, we
      used 17 DNAs extracted from vaginal swabs and 12 DNAs extracted from stool
      samples to study the influence of nested PCR amplification of the 16S rRNA gene
      on the estimation of microbial community structure using Illumina MiSeq
      sequencing. Nested and standard PCR methods were compared on alpha- and beta
      diversity metrics and relative abundances of bacterial genera. The effects of
      number of cycles in the first round of PCR (10 vs. 20) and microbial diversity
      (relatively low in vagina vs. high in stool) were also investigated. Vaginal swab
      samples showed no significant difference in alpha diversity or community
      structure between nested PCR and standard PCR (one round of 40 cycles). Stool
      samples showed significant differences in alpha diversity (except Shannon's
      index) and relative abundance of 13 genera between nested PCR with 20 cycles in
      the first round and standard PCR (P<0.01), but not between nested PCR with 10
      cycles in the first round and standard PCR. Operational taxonomic units (OTUs)
      that had low relative abundance (sum of relative abundance <0.167) accounted for
      most of the distortion (>27% of total OTUs in stool). CONCLUSIONS: Nested PCR
      introduced bias in estimated diversity and community structure. The bias was more
      significant for communities with relatively higher diversity and when more cycles
      were applied in the first round of PCR. We conclude that nested PCR could be used
      when standard PCR does not work. However, rare taxa detected by nested PCR should
      be validated by other technologies.

PMID- 26196513
TI  - Snake Cathelicidin NA-CATH and Smaller Helical Antimicrobial Peptides Are
      Effective against Burkholderia thailandensis.
AB  - Burkholderia thailandensis is a Gram-negative soil bacterium used as a model
      organism for B. pseudomallei, the causative agent of melioidosis and an organism
      classified category B priority pathogen and a Tier 1 select agent for its
      potential use as a biological weapon. Burkholderia species are reportedly "highly
      resistant" to antimicrobial agents, including cyclic peptide antibiotics, due to
      multiple resistance systems, a hypothesis we decided to test using antimicrobial
      (host defense) peptides. In this study, a number of cationic antimicrobial
      peptides (CAMPs) were tested in vitro against B. thailandensis for both
      antimicrobial activity and inhibition of biofilm formation. Here, we report that
      the Chinese cobra (Naja atra) cathelicidin NA-CATH was significantly
      antimicrobial against B. thailandensis. Additional cathelicidins, including the
      human cathelicidin LL-37, a sheep cathelicidin SMAP-29, and some smaller ATRA
      peptide derivatives of NA-CATH were also effective. The D-enantiomer of one small
      peptide (ATRA-1A) was found to be antimicrobial as well, with EC50 in the range
      of the L-enantiomer. Our results also demonstrate that human alpha-defensins (HNP
      1 & -2) and a short beta-defensin-derived peptide (Peptide 4 of hBD-3) were not
      bactericidal against B. thailandensis. We also found that the cathelicidin
      peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to
      prevent biofilm formation of B. thailandensis. Additionally, we show that LL-37
      and its D-enantiomer D-LL-37 can disperse pre-formed biofilms. These results
      demonstrate that although B. thailandensis is highly resistant to many
      antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing
      peptides, some antimicrobial peptides including the elapid snake cathelicidin NA
      CATH exert significant antimicrobial and antibiofilm activity towards B.
      thailandensis. 

PMID- 26196514
TI  - Trends and Patterns of Urodynamic Studies in U.S. Males, 2000-2012.
AB  - OBJECTIVE: To evaluate trends in urodynamic procedures in the U.S. males from
      2000-2012 and determine if a 2010 decline in reimbursement was associated with
      decreased utilization. SUBJECTS AND METHODS: We analyzed 2000-2012 administrative
      healthcare claims from Truven Health's Marketscan Database and evaluated males
      >=18 years of age. We identified cystometrograms and any concurrent procedures
      using procedure billing codes. Covariates included age, year of cystometrogram,
      region and associated diagnosis codes. We estimated standardized cystometrogram
      utilization rates per 10,000 person-years (PY). We used age, region, and calendar
      year adjusted Poisson regression models to estimate the independent effect of
      calendar year and region. RESULTS: During 127,558,186 PY of observation, we
      identified 153,168 cystometrograms for an overall utilization rate of 12.0 per
      10,000 PY (95% CI 11.9-12.1). Cystometrogram utilization increased with age,
      peaking at age 85 with a rate of 77.7 per 10,000 PY (95% CI 74.7-80.7). Adjusted
      cystometrogram utilization rate ratios show that compared to a referent of 2000
      2004, utilization was significantly higher in each year 2005 to 2011 among all
      patients and in 2012 among patients >= 65. Standardized utilization rates peaked
      in 2008 at 12.4 per 10,000 PY (95% CI 12.2-12.6), remained elevated until 2010,
      then decreased slightly in 2011 and substantially in 2012 to 8.5 per 10,000 PY
      (95% CI 8.4-8.7). CONCLUSIONS: Utilization of urodynamic procedures increased
      until 2010 and decreased thereafter. Utilization was greatest among men older
      than 65.

PMID- 26196515
TI  - The Kinetic Response of the Proteome in A549 Cells Exposed to ZnSO4 Stress.
AB  - Zinc, an essential trace element, is involved in many important physiological
      processes. Cell responses to zinc stress show time-dependent effects besides
      concentration-dependence and tissue-specificity. Herein, we investigated the time
      dependent differential expression of the proteome in A549 cells after
      administered with ZnSO4 for both 9 and 24 h using 2DE. 123 differentially
      expressed protein spots were detected, most of which were up-regulated by Zn2+
      treatment. Interestingly, 49 proteins exhibited significant differential
      expression repeatedly during these two treatment periods, and moreover showed a
      conserved change with different ratios and four time-dependent expression
      patterns. Pattern 1 (up-regulated with rapid initial induction and subsequent
      repression) and pattern 4 (down-regulated with steady repression) were the
      predominant expression patterns. The abundances of the proteins in patterns 1 and
      4 after 24 h of zinc treatment are always lower than that after 9 h, indicating
      that exogenous zinc reduced the expression of proteins in cells after 24 h or
      longer. Importantly, these findings could also reflect the central challenge in
      detecting zinc homeostasis proteins by 2DE or other high throughput analytical
      methods resulting from slight variation in protein expression after certain
      durations of exogenous zinc treatment and/or low inherent protein content in
      cells. These time-dependent proteome expression patterns were further validated
      by measuring dynamic changes in protein content in cells and in expression of two
      proteins using the Bradford method and western blotting, respectively. The time
      dependent changes in total zinc and free Zn2+ ion contents in cells were measured
      using ICP-MS and confocal microscopy, respectively. The kinetic process of zinc
      homeostasis regulated by muffling was further revealed. In addition, we
      identified 50 differentially expressed proteins which are predominantly involved
      in metabolic process, cellular process or developmental process, and function as
      binding, catalytic activity or structural molecule activity. This study further
      elucidates our understanding of dynamic nature of the cellular response to zinc
      stress and the mechanism of zinc homeostasis.

PMID- 26196516
TI  - The Impact of Coexisting Asthma, Chronic Obstructive Pulmonary Disease and
      Tuberculosis on Survival in Patients with Lung Squamous Cell Carcinoma.
AB  - BACKGROUND: Pulmonary diseases [asthma, chronic obstructive pulmonary disease
      (COPD), and tuberculosis (TB)] are associated with lung cancer mortality.
      However, the relationship between coexisting pulmonary diseases and survival in
      patients with lung squamous cell carcinoma (SqCC) has not been well defined.
      METHODS: Patients newly diagnosed with SqCC between 2003 and 2008 were identified
      by linking the National Health Insurance Research Database and Taiwan Cancer
      Registry Database. Cases with SqCC were followed up until death, loss to follow
      up, or study end in 2010. Information on health status, date of death and the
      main causes of death was ascertained from the National Death Registry Database.
      Cox proportional hazard regression was used to calculate the hazard ratio (HR) of
      coexisting asthma, COPD and/or TB. RESULTS: During the study period, a total of
      5406 cases with SqCC were enrolled. For all cause-mortality, HRs were 1.08 [95%
      confidence interval (CI), 0.99-1.18], 1.04 (95% CI, 0.97-1.12), and 1.14 (95% CI,
      1.00-1.31) for individuals with asthma, COPD, and TB, respectively. Specifically,
      among men with coexisting pulmonary diseases, the HRs were 1.56 (95% CI, 1.23
      1.97) and 1.11 (95% CI, 1.00-1.24) for individuals with asthma+COPD+TB and
      asthma+COPD, respectively. Among male patients with stage III SqCC, HRs were 3.41
      (95%CI, 1.27-9.17) and 1.65 (95%CI, 1.10-2.47) for individuals with asthma+TB and
      asthma+COPD+TB, respectively. Among male patients with stage IV SqCC, HRs were
      1.40 (95%CI, 1.00-1.97) and 1.25 (95%CI, 1.03-1.52) for individuals with asthma+
      COPD+TB and asthma. Among female patients with stage I and II, HR was 0.19
      (95%CI, 005-0.77) for individuals with asthma. CONCLUSIONS: Coexisting pulmonary
      diseases increased the risk of mortality from SqCC in male patients. For female
      patients with early stage SqCC, pre-existing asthma decreased mortality. These
      patients deserve greater attention while undergoing cancer treatment.

PMID- 26196517
TI  - Identification of Androgen Receptor Splice Variants in the Pten Deficient Murine
      Prostate Cancer Model.
AB  - Androgen receptor (AR) variants are associated with resistance to anti androgen
      therapy both in human prostate cancer cell lines and clinical samples. These
      observations support the hypothesis that AR isoform accumulation is a consequence
      of selective therapeutic pressure on the full length AR. The Pten deficient
      prostate cancer model proceeds with well-defined kinetics including progression
      to castration resistant prostate cancer (CRPC). While surgical castration and
      enzalutamide treatments yield an initial therapeutic response, Pten-/-epithelia
      continue to proliferate yielding locally invasive primary tumor pathology. That
      most epithelium remains AR positive, but ligand independent, suggests the
      presence of oncogenic AR variants. To address this hypothesis, we have used a
      panel of recently described Pten-/- tumor cell lines derived from both from
      hormone intact (E4, E8) and castrated Pten mutants (cE1, cE2) followed by RACE
      PCR to identify and characterize three novel truncated, amino terminus containing
      AR variants (mAR-Va, b, c). Variants appear not only conserved throughout
      progression but are correlated with nearly complete loss of full length AR (AR
      FL) at castrate androgen levels. The overexpression of variants leads to enhanced
      transcriptional activity of AR while knock down studies show reduced
      transcriptional output. Collectively, the identification of truncated AR variants
      in the conditional PTEN deletion model supports a role for maintaining the CRPC
      phenotype and provides further therapeutic applications of this preclinical
      model. 

PMID- 26196518
TI  - The Effect of Continuous and Discretized Presentations of Concurrent Augmented
      Visual Biofeedback on Postural Control in Quiet Stance.
AB  - The purpose of this study was to evaluate the effect of a continuous and a
      discretized Visual Biofeedback (VBF) on balance performance in upright stance.
      The coordinates of the Centre of Pressure (CoP), extracted from a force plate,
      were processed in real-time to implement the two VBFs, administered to two groups
      of 12 healthy participants. In the first group, a representation of the CoP was
      continuously shown, while in the second group, the discretized VBF was provided
      at an irregular frequency (that depended on the subject's performance) by
      displaying one out of a set of five different emoticons, each corresponding to a
      specific area covered by the current position of the CoP. In the first case,
      participants were asked to maintain a white spot within a given square area,
      whereas in the second case they were asked to keep the smiling emoticon on.
      Trials with no VBF were administered as control. The effect of the two VBFs on
      balance was studied through classical postural parameters and a subset of
      stabilogram diffusion coefficients. To quantify the amount of time spent in
      stable conditions, the percentage of time during which the CoP was inside the
      stability area was calculated. Both VBFs improved balance maintainance as
      compared to the absence of any VBF. As compared to the continuous VBF, in the
      discretized VBF a significant decrease of sway path, diffusion and Hurst
      coefficients was found. These results seem to indicate that a discretized VBF
      favours a more natural postural behaviour by promoting a natural intermittent
      postural control strategy.

PMID- 26196520
TI  - A One Pot Synthesis of Novel Bioactive Tri-Substitute-Condensed-Imidazopyridines
      that Targets Snake Venom Phospholipase A2.
AB  - Drugs such as necopidem, saripidem, alpidem, zolpidem, and olprinone contain
      nitrogen-containing bicyclic, condensed-imidazo[1,2-alpha]pyridines as bioactive
      scaffolds. In this work, we report a high-yield one pot synthesis of 1-(2-methyl
      8-aryl-substitued-imidazo[1,2-alpha]pyridin-3-yl)ethan-1-onefor the first-time.
      Subsequently, we performed in silico mode-of-action analysis and predicted that
      the synthesized imidazopyridines targets Phospholipase A2 (PLA2). In vitro
      analysis confirmed the predicted target PLA2 for the novel imidazopyridine
      derivative1-(2-Methyl-8-naphthalen-1-yl-imidazo [1,2-alpha]pyridine-3-yl)
      ethanone (compound 3f) showing significant inhibitory activity towards snake
      venom PLA2 with an IC50 value of 14.3 MUM. Evidently, the molecular docking
      analysis suggested that imidazopyridine compound was able to bind to the active
      site of the PLA2 with strong affinity, whose affinity values are comparable to
      nimesulide. Furthermore, we estimated the potential for oral bioavailability by
      Lipinski's Rule of Five. Hence, it is concluded that the compound 3f could be a
      lead molecule against snake venom PLA2. 

PMID- 26196521
TI  - Nitro-Assisted Bronsted Acid Catalysis: Application to a Challenging Catalytic
      Azidation.
AB  - A cocatalytic effect of nitro compounds is described for the B(C6F5)3.H2O
      catalyzed azidation of tertiary aliphatic alcohols, enabling catalyst turnover
      for the first time and with a broad range of substrates. Kinetic investigations
      into this surprising effect reveal that nitro compounds induce a switch from
      first order concentration dependence in Bronsted acid to second order
      concentration dependence in Bronsted acid and second order dependence in the
      nitro compounds. Kinetic, electronic, and spectroscopic evidence suggests that
      higher order hydrogen-bonded aggregates of nitro compounds and acids are the
      kinetically competent Bronsted acid catalysts. Specific weak H-bond accepting
      additives may offer a new general approach to accelerating Bronsted acid
      catalysis in solution. 

PMID- 26196519
TI  - Increased Insulin following an Oral Glucose Load, Genetic Variation near the
      Melatonin Receptor MTNR1B, but No Biochemical Evidence of Endothelial Dysfunction
      in Young Asian Men and Women.
AB  - AIM: To identify biochemical and genetic variation relating to increased risk of
      developing type 2 diabetes mellitus and cardiovascular disease in young, lean
      male and female adults of different ethnicities. METHOD: Fasting blood and urine
      and non-fasting blood following oral glucose intake were analysed in 90
      Caucasians, South Asians and South East/East Asians. RESULTS: There were no
      differences in age, birthweight, blood pressure, body mass index, percent body
      fat, total energy, percentage of macronutrient intake, microalbumin, leptin,
      cortisol, adrenocorticotropic hormone, nitric oxide metabolites, C-reactive
      protein, homocysteine, tumor necrosis factor-alpha, interleukin-6, von Willebrand
      factor, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, and
      tissue plasminogen activator. Fasting total cholesterol (P = .000), triglycerides
      (P = .050), low density lipoprotein (P = .009) and non-fasting blood glucose (15
      min) (P = .024) were elevated in South Asians compared with Caucasians, but there
      was no significant difference in glucose area under curve (AUC). Non-fasting
      insulin in South Asians (15-120 min), in South East/East Asians (60-120 min), and
      insulin AUC in South Asians and South East/East Asians, were elevated compared
      with Caucasians (P<=0.006). The molar ratio of C-peptide AUC/Insulin AUC (P =
      .045) and adiponectin (P = .037) were lower in South Asians compared with
      Caucasians. A significant difference in allele frequency distributions in
      Caucasians and South Asians was found for rs2166706 (P = 0.022) and rs10830963 (P
      = 0.009), which are both near the melatonin receptor MTNR1B. CONCLUSIONS:
      Elevated non-fasting insulin exists in young South Asians of normal fasting
      glucose and insulin. Hepatic clearance of insulin may be reduced in South Asians.
      No current biochemical evidence exists of endothelial dysfunction at this stage
      of development. MTNR1B signalling may be a useful therapeutic target in Asian
      populations in the prevention of type 2 diabetes mellitus.

PMID- 26196522
TI  - Safety and Efficacy of Dexmedetomidine as a Sedative Agent for Performing Awake
      Intubation: A Meta-analysis.
AB  - To compare the efficacy and safety of dexmedetomidine with other alternative
      sedative agents used for performing awake intubation. We conducted a meta
      analysis of randomized controlled trials (RCTs) that compared the effects of
      dexmedetomidine with other alternative sedative agents used during awake
      intubation. The biomedical databases PubMed, Science Direct, and the Cochrane
      Library were searched for relevant RCTs with no restriction on the language of
      publication. The efficacy (level of sedation, success rate for intubation at the
      first attempt, intubation time, intubation conditions, and patient satisfaction)
      and safety (incidence of hypertension, hypotension, tachycardia, bradycardia,
      hypoxia, postsurgical memory, hoarseness, and sore throat) were assessed.
      Thirteen RCTs with a combined subject population of 591 patients came within the
      purview of this meta-analysis. Use of dexmedetomidine was associated with a
      higher Ramsay sedation scale score [mean difference (MD): 1.02, 95% confidence
      interval (CI), 0.77-1.28, P < 0.00001], vocal cord movement score (MD = 0.72, 95%
      CI, 0.20-1.24, P = 0.007), coughing scores (MD = 0.66, 95% CI, 0.10-1.22, P =
      0.02), limb movement scores (MD = 0.69, 95% CI, 0.47-0.91, P < 0.00001);
      increased risk of bradycardia [relative risk (RR): 3.03, 95% CI, 1.38-6.68, P =
      0.006] and hypotension (RR: 2.87, 95% CI, 1.44-5.75, P = 0.003); and lower risk
      of hypoxia (RR: 0.32, 95% CI, 0.15-0.70; P = 0.004) and postsurgical memory (RR:
      0.50, 95% CI, 0.35-0.72, P = 0.0002). As indicated by our results,
      dexmedetomidine appears to be an effective and well-tolerated agent for
      performing awake intubation. Its use was associated with better intubation
      conditions, preservation of airway patency, and reduced recall of intubation, as
      compared with the traditional sedative agents. The risk of bradycardia and
      hypotension was significantly higher with dexmedetomidine as compared with that
      with other sedatives. However, these were easily managed with atropine and
      vasoactive agents.

PMID- 26196523
TI  - Erythema Multiforme Associated With Misoprostol: A Case Report.
AB  - A 33-year-old healthy woman at 6 weeks of gestation without any underlying
      disease developed erythema multiforme (EM) after misoprostol. She had no history
      of herpes simplex virus infection and drug allergy to nonsteroidal anti
      inflammatory drugs and antibiotic agents. Medical abortion was performed at 6
      weeks' gestation. Later day, the patient developed oral lesions as several white
      bullae lesions in her buccal mucosa and hyperkeratotic lip plaques with mild
      pain. Then, lesions resolved within approximately 3 weeks. Microscopic finding of
      oral biopsy from beneath the tongue and lesions was performed. The result was
      consistent with erosive mucosa with granulation tissue formation and acute
      inflammation in favor of EM. This is the case report of probable misoprostol
      induced EM. Because EM may produce in skin as a Stevens-Johnson syndrome in
      subsequent attack, monitoring of this adverse drug reaction should be considered
      for proper management and follow-up. 

PMID- 26196524
TI  - Delayed Myocardial Infarction Associated With Rituximab Infusion: A Case Report
      and Literature Review.
AB  - To report a case of delayed myocardial infraction after rituximab infusion. A 52
      year-old woman with history of refractory idiopathic thrombocytopenic purpura had
      hypertension, seizure, and mild coronary artery disease and received rituximab;
      after 24 hours, she returned back with chest pain, nausea, and vomiting. Her
      electrocardiogram showed a ST-elevation in the II, III, aVF, and aVR lead and ST
      depression in I and aVL lead; after another complementary test, the myocardial
      infraction was confirmed. The patient was sent to the intensive care unit, and
      after 8-day hospitalization, she was discharged. Based on the Naranjo Probability
      Scale, the likelihood of rituximab-induced acute myocardial infarction in this
      case was probable. Rituximab is generally well tolerated; however, cardiovascular
      effects of this drug can be fatal. The side effects usually occur during or a
      short time after infusion; this case demonstrated that rituximab side effects may
      occur with delay. This case demonstrates, although a rare phenomenon, myocardial
      infraction may occur after 24 hours and clinicians should be aware of this fatal
      effect even after a period of time in patients receiving rituximab, especially in
      patients with history of coronary artery disease. 

PMID- 26196525
TI  - Seasonal Patterns of Buruli Ulcer Incidence, Central Africa, 2002-2012.
AB  - To determine when risk for Buruli ulcer is highest, we examined seasonal patterns
      in a highly disease-endemic area of Cameroon during 2002-2012. Cases peaked in
      March, suggesting that risk is highest during the high rainy season. During and
      after this season, populations should increase protective behaviors, and case
      detection efforts should be intensified. 

PMID- 26196526
TI  - Series of SHG Materials Based on Lanthanide Borate-Acetate Mixed Anion Compounds.
AB  - The first examples of lanthanide borate-acetate mixed anion compounds, namely,
      Ln2(CH3CO2)2[B5O9(OH)].H2O (Ln = La 1; Ce 2; Pr 3), were synthesized under
      hydrothermal conditions. These compounds are isostructural and crystallize in
      polar space group Cc. They display a unique three-dimensional (3D) framework
      built by a 3D network of lanthanide borate further decorated by acetate anions.
      The borate anion exhibits a 2D layer in the ac plane with large 9-member rings
      (MRs) which are filled by lanthanide(III) ions into a {Ln[B5O9(OH)]}(-) 2D layer.
      Adjacent {Ln[B5O9(OH)]}(-) layers are bridged by remaining lanthanide (III) ions
      to form a 3D network of lanthanide borate. It is noteworthy that
      Ln2(CH3CO2)2[B5O9(OH)].H2O (Ln = La 1; Ce 2; Pr 3) can be changed into
      Ln2(CH3CO2)2[B5O9(OH)] (Ln = La 4; Ce 5; Pr 6) under heating at 500 K. Compounds
      1-4 display moderate SHG signals of about 2.0, 1.0, 1.4, and 2.5 times that of
      KH2PO4, respectively, and they are phase matchable. Their SHG responses mainly
      arise from the synergistic polarization effects of both asymmetric borate
      clusters and pi-conjugated CH3COO(-) anions. 

PMID- 26196527
TI  - The effect of an anaesthetic patient information video on perioperative anxiety:
      A randomised study.
AB  - BACKGROUND: Despite growing evidence that an educational anaesthesia video can
      effectively reduce perioperative anxiety, the ideal medium for addressing
      perioperative anxiety is unclear. OBJECTIVE: The purpose of this study was to
      investigate the effect of viewing an anaesthetic patient information video on
      anxiety levels in patients scheduled to undergo surgery. DESIGN: A randomised
      controlled trial. SETTING: Pingtung Christian Hospital (PTCH), Taiwan. PATIENTS:
      One hundred patients were randomised to either an experimental group (n = 50) or
      a control group (n = 50). INTERVENTIONS: At the preoperative clinic, the
      experimental group watched the an 8 minute educational anaesthetic video, whereas
      the control group received a standard 8-min verbal briefing on anaesthesia after
      preoperative assessment. MAIN OUTCOMES MEASURES: The Chinese version of the
      Spielberger state trait anxiety inventory, which included a state scale (STAI-S)
      and a trait scale (STAI-T), was performed in the preoperative clinic (T1) before
      anaesthetic preassessment, at the preoperative holding area just before surgery
      (T2) and again on the third day after surgery (T3). Scores for overall
      satisfaction with medical care were obtained on the third day after surgery. For
      two time interval comparisons, effect size was used to standardise the extent of
      change as measured by STAI-S. RESULTS: After the educational intervention, state
      anxiety was lower in the experimental group than in the control group at both T2
      (42.9 +/- 6.5 vs. 45.0 +/- 12.7) and T3 (40.2 +/- 5.3 vs. 48.8 +/- 8.5). Compared
      with control group, the experimental group had a larger effect size at T2 and T3
      (-0.65 and -0.36, respectively). Overall satisfaction was significantly higher in
      the experimental group than in the control group (P < 0.05). CONCLUSION:
      Perioperative anxiety was significantly reduced and overall patient satisfaction
      increased after viewing a preoperative educational anaesthesia video compared
      with a standard verbal briefing on anaesthesia.

PMID- 26196528
TI  - Disposition of inorganic mercury in pregnant rats and their offspring.
AB  - Environmental toxicants such as methylmercury have been shown to negatively
      impact fetal health. Despite the prevalence of inorganic mercury (Hg(2+)) in the
      environment and the ability of methylmercury to biotransform into Hg(2+), little
      is known about the ability of Hg(2+) to cross the placenta into fetal tissues.
      Therefore, it is important to understand the handing and disposition of Hg(2+) in
      the reproductive system. The purpose of the current study was to assess the
      disposition and transport of Hg(2+) in placental and fetal tissues, and to test
      the hypothesis that acute renal injury in dams can alter the accumulation of
      Hg(2+) in fetal tissues. Pregnant Wistar rats were injected intravenously with
      0.5 or 2.5 MUmol kg(-1) HgCl2 for 6 or 48 h and the disposition of Hg(2+) was
      measured. Accumulation of Hg(2+) in the placenta was rapid and dose-dependent.
      Very little Hg(2+) was eliminated during the initial 48 h after exposure. When
      dams were exposed to the low dose of HgCl2, fetal accumulation of Hg(2+)
      increased between 6h and 48 h, while at the higher dose, accumulation was similar
      at each time point. Within fetal organs, the greatest concentration of Hg(2+)
      (nmol/g) was localized in the kidneys, followed by the liver and brain. A dose
      dependent increase in the accumulation of Hg(2+) in fetal organs was observed,
      suggesting that continued maternal exposure may lead to increased fetal exposure.
      Taken together, these data indicate that Hg(2+) is capable of crossing the
      placenta and gaining access to fetal organs in a dose-dependent manner.

PMID- 26196529
TI  - Conceptual model for assessing criteria air pollutants in a multipollutant
      context: A modified adverse outcome pathway approach.
AB  - Air pollution consists of a complex mixture of particulate and gaseous
      components. Individual criteria and other hazardous air pollutants have been
      linked to adverse respiratory and cardiovascular health outcomes. However,
      assessing risk of air pollutant mixtures is difficult since components are
      present in different combinations and concentrations in ambient air. Recent
      mechanistic studies have limited utility because of the inability to link
      measured changes to adverse outcomes that are relevant to risk assessment. New
      approaches are needed to address this challenge. The purpose of this manuscript
      is to describe a conceptual model, based on the adverse outcome pathway approach,
      which connects initiating events at the cellular and molecular level to
      population-wide impacts. This may facilitate hazard assessment of air pollution
      mixtures. In the case reports presented here, airway hyperresponsiveness and
      endothelial dysfunction are measurable endpoints that serve to integrate the
      effects of individual criteria air pollutants found in inhaled mixtures. This
      approach incorporates information from experimental and observational studies
      into a sequential series of higher order effects. The proposed model has the
      potential to facilitate multipollutant risk assessment by providing a framework
      that can be used to converge the effects of air pollutants in light of common
      underlying mechanisms. This approach may provide a ready-to-use tool to
      facilitate evaluation of health effects resulting from exposure to air pollution
      mixtures. 

PMID- 26196530
TI  - Oxidative stress-mediated inhibition of intestinal epithelial cell proliferation
      by silver nanoparticles.
AB  - Given the increasing use of silver nanoparticles (Ag NP) by the food and food
      packaging industries, this study investigated potential consequences of Ag NP
      ingestion in intestinal epithelial C2BBe1 cells. Treatment of proliferating cells
      (<10,000 cells/cm(2)) with 0.25 MUg/cm(2) (1.25 MUg/mL) of 23 nm Ag NP for 24 h
      induced 15% necrotic cell death and an 80% reduction in metabolic activity and
      decreased the GSH/GSSG ratio, indicating oxidative stress. G2/M phase cell cycle
      arrest and complete inhibition of cell proliferation was also induced by Ag NP
      treatment. Simulated in vitro digestion of Ag NP prior to cell exposure required
      the use of slightly higher doses to induce the same toxicity, likely due to
      slower Ag dissolution. Treatment of cells with silica, titania, and ZnO NP
      partially inhibited cell proliferation, but inhibition at low doses was unique to
      Ag NP. These data suggest that Ag NP induces oxidative stress, cell cycle arrest,
      and the inhibition of cell proliferation. However, toxicity and induction of
      oxidative stress were not observed in confluent cells (>100,000 cells/cm(2))
      treated with 10 MUg/cm(2) (40-50 MUg/mL) Ag NP, indicating that these cells are
      less sensitive to Ag NP.

PMID- 26196531
TI  - Fabrication of Three-Layer-Component Organoclay Hybrid Films with Reverse
      Deposition Orders by a Modified Langmuir-Schaefer Technique and Their
      Pyroelectric Currents Measured by a Noncontact Method.
AB  - In an aqueous clay mineral (montmorillonite) dispersion at a low concentration,
      isolated clay nanosheets with negative charges were suspended. When a solution of
      amphiphilic octadecylammonium chloride (ODAH(+)Cl(-)) was spread on an air
      dispersion interface, the clay nanosheets were adsorbed on the ODAH(+) cations at
      the interface to form a stable ultrathin floating film. The floating film was
      transferred onto a substrate by the Schaefer method, and then the film was
      immersed in a [Ru(dpp)3]Cl2 (dpp = 4,7-diphenyl-1,10-phenanthroline) solution.
      The Ru(II) complex cations were adsorbed on the film surface because the film
      surface possessed a cation-exchange ability. The layers of ODAH(+), clay
      nanosheets, and [Ru(dpp)3](2+) were deposited in this order. By repeating these
      procedures, three-layer-component films were fabricated (OCR films). In a similar
      way, three-layer-component films in which the layers of [Ru(dpp)3](2+), clay
      nanosheets, and ODAH(+) were deposited in the reverse order (RCO films) were
      prepared by spreading a [Ru(dpp)3](ClO4)2 solution and immersing the films in an
      ODAH(+)Cl(-) solution. Both OCR and RCO films were characterized by surface
      pressure-molecular area (pi-A) curve measurements, IR and visible spectroscopy,
      and the XRD method. The OCR and RCO film systems possessed nearly the same
      properties in the densities of ODAH(+) and [Ru(dpp)3](2+) and the tilt angle of
      the Ru(II) complex cation, although the layer distance for the RCO film was a
      little longer than that for the OCR film and the layered structure for the RCO
      film was less ordered than that for the OCR film. Pyroelectric currents for the
      films were measured by a noncontact method using an (241)Am radioactive
      electrode. When the films were heated, the pyroelectric currents were observed
      and the current directions for the OCR and RCO films were different. This was
      clear evidence that the layer order in the OCR film was reverse of that in the
      RCO film. 

PMID- 26196533
TI  - The use of collagen-based scaffolds to simulate prostate cancer bone metastases
      with potential for evaluating delivery of nanoparticulate gene therapeutics.
AB  - Prostate cancer bone metastases are a leading cause of cancer-related death in
      men with current treatments offering only marginally improved rates of survival.
      Advances in the understanding of the genetic basis of prostate cancer provide the
      opportunity to develop gene-based medicines capable of treating metastatic
      disease. The aim of this work was to establish a 3D cell culture model of
      prostate cancer bone metastasis using collagen-based scaffolds, to characterise
      this model, and to assess the potential of the model to evaluate delivery of gene
      therapeutics designed to target bone metastases. Two prostate cancer cell lines
      (PC3 and LNCaP) were cultured in 2D standard culture and compared to 3D cell
      growth on three different collagen-based scaffolds (collagen and composites of
      collagen containing either glycosaminoglycan or nanohydroxyapatite). The 3D model
      was characterised for cell proliferation, viability and for matrix
      metalloproteinase (MMP) enzyme and Prostate Specific Antigen (PSA) secretion.
      Chemosensitivity to docetaxel treatment was assessed in 2D in comparison to 3D.
      Nanoparticles (NPs) containing siRNA formulated using a modified cyclodextrin
      were delivered to the cells on the scaffolds and gene silencing was quantified.
      Both prostate cancer cell lines actively infiltrated and proliferated on the
      scaffolds. Cell culture in 3D resulted in reduced levels of MMP1 and MMP9
      secretion in PC3 cells. In contrast, LNCaP cells grown in 3D secreted elevated
      levels of PSA, particularly on the scaffold composed of collagen and
      glycosaminoglycans. Both cell lines grown in 3D displayed increased resistance to
      docetaxel treatment. The cyclodextrin.siRNA nanoparticles achieved cellular
      uptake and knocked down the endogenous GAPDH gene in the 3D model. In conclusion,
      development of a novel 3D cell culture model of prostate cancer bone metastasis
      has been initiated resulting, for the first time, in the successful delivery of
      gene therapeutics in a 3D in vitro model. Further enhancement of this model will
      help elucidate the pathogenesis of prostate cancer and also accelerate the design
      of effective therapies which can penetrate into the bone microenvironment for
      prostate cancer therapy.

PMID- 26196532
TI  - Dermal delivery of HSP47 siRNA with NOX4-modulating mesoporous silica-based
      nanoparticles for treating fibrosis.
AB  - Fibrotic diseases such as scleroderma have been linked to increased oxidative
      stress and upregulation of pro-fibrotic genes. Recent work suggests a role of
      NADPH oxidase 4 (NOX4) and heat shock protein 47 (HSP47) in inducing excessive
      collagen synthesis, leading to fibrotic diseases. Herein, we elucidate the
      relationship between NOX4 and HSP47 in fibrogenesis and propose to modulate them
      altogether as a new strategy to treat fibrosis. We developed a nanoparticle
      platform consisting of polyethylenimine (PEI) and polyethylene glycol (PEG)
      coating on a 50-nm mesoporous silica nanoparticle (MSNP) core. The nanoparticles
      effectively delivered small interfering RNA (siRNA) targeting HSP47 (siHSP47) in
      an in vitro model of fibrosis based on TGF-beta stimulated fibroblasts. The MSNP
      core also imparted an antioxidant property by scavenging reactive oxygen species
      (ROS) and subsequently reducing NOX4 levels in the in vitro fibrogenesis model.
      The nanoparticle was far superior to n-acetyl cysteine (NAC) at modulating pro
      fibrotic markers. In vivo evaluation was performed in a bleomycin-induced
      scleroderma mouse model, which shares many similarities to human scleroderma
      disease. Intradermal administration of siHSP47-nanoparticles effectively reduced
      HSP47 protein expression in skin to normal level. In addition, the antioxidant
      MSNP also played a prominent role in reducing the pro-fibrotic markers, NOX4,
      alpha smooth muscle actin (alpha-SMA), and collagen type I (COL I), as well as
      skin thickness of the mice.

PMID- 26196534
TI  - Characterization of human ethmoid sinus mucosa derived mesenchymal stem cells
      (hESMSCs) and the application of hESMSCs cell sheets in bone regeneration.
AB  - Mesenchymal stem cells (MSCs) have been extensively applied in the field of
      tissue regeneration. MSCs derived from various tissues exhibit different
      characteristics. In this study, a cluster of cells were isolated from human
      ethmoid sinus mucosa membrane and termed as hESMSCs. hESMSCs was demonstrated to
      have MSC-specific characteristics of self-renewal and tri-lineage
      differentiation. In particular, hESMSCs displayed strong osteogenic
      differentiation potential, and also remarkably promoted the proliferation and
      osteogenesis of rat bone marrow mesenchymal stem cells (rBMSCs) in vitro. Next,
      hESMSCs were prepared into a cell sheet and combined with a PSeD scaffold seeded
      with rBMSCs to repair critical-sized calvarial defects in rats, which showed
      excellent reparative effects. Additionally, ELISA assays revealed that secreted
      cytokines, such as BMP-2, BMP-4 and bFGF, were higher in the hESMSCs conditioned
      medium, and immunohistochemistry validated that hESMSCs cell sheet promoted the
      expression of BMP signaling downstream genes in newly formed bone. In conclusion,
      hESMSCs were demonstrated to be a class of mesenchymal stem cells that possessed
      high self-renewal capacity along with strong osteogenic potential, and the cell
      sheet of hESMSCs could remarkably promote new bone regeneration, indicating that
      hESMSCs cell sheet could serve as a novel and promising alternative strategy in
      the management of bone regeneration.

PMID- 26196536
TI  - Radical Pathways for the Prebiotic Formation of Pyrimidine Bases from Formamide.
AB  - The prebiotic formation of nucleobases, the building blocks of RNA/DNA, is of
      current interest. Highly reactive radical species present in the atmosphere under
      irradiation have been suggested to be involved in the prebiotic synthesis of
      nucleobases from formamide (FM). We studied several free radical reaction
      pathways for the synthesis of pyrimidine bases (cytosine, uracil, and thymine)
      from FM under cold conditions. These pathways are theoretically determined using
      density functional theory (DFT) computations to examine their kinetic and
      thermodynamic feasibilities. These free radical reaction pathways share some
      common reaction types such as H-rearrangement, (*)H/(*)OH/(*)NH2 radical loss,
      and intramolecular radical cyclization. The rate-determining steps in these
      pathways are characterized with low energy barriers. The energy barriers of the
      ring formation steps are in the range of 3-7 kcal/mol. Although DFT methods are
      known to significantly underestimate the barriers for addition of (*)H radical to
      neutral species, many of these reactions are highly exergonic with energy release
      of -15 to -52 kcal/mol and are thus favorable. Among the suggested pathways for
      formation of cytosine (main route, routes 7a and 1a), uracil (main route, routes
      7b and 1b), and thymine (main route and route 26a), the main routes are in
      general thermodynamically more exergonic and more kinetically favored than other
      alternative routes with lower overall energy barriers. The reaction energies
      released following formation of cytosine, uracil, and thymine from FM via the
      main radical routes amount to -59, -81, and -104 kcal/mol, respectively.
      Increasing temperature induces unfavorable changes in both kinetic and
      thermodynamic aspects of the suggested routes. However, the main routes are still
      more favored than the alternative pathways at the temperature up to the boiling
      point of FM. 

PMID- 26196535
TI  - A novel crosslinking method for improved tear resistance and biocompatibility of
      tissue based biomaterials.
AB  - Over 300,000 heart valve replacements are performed annually to replace stenotic
      and regurgitant heart valves. Bioprosthetic heart valves (BHVs), derived from
      glutaraldehyde crosslinked (GLUT) porcine aortic valve leaflets or bovine
      pericardium are often used. However, valve failure can occur within 12-15 years
      due to calcification and/or progressive degeneration. In this study, we have
      developed a novel fabrication method that utilizes carbodiimide, neomycin
      trisulfate, and pentagalloyl glucose crosslinking chemistry (TRI) to better
      stabilize the extracellular matrix of porcine aortic valve leaflets. We
      demonstrate that TRI treated leaflets show similar biomechanics to GLUT
      crosslinked leaflets. TRI treated leaflets had better resistance to enzymatic
      degradation in vitro and demonstrated better tearing toughness after challenged
      with enzymatic degradation. When implanted subcutaneously in rats for up to 90
      days, GLUT control leaflets calcified heavily while TRI treated leaflets resisted
      calcification, retained more ECM components, and showed better biocompatibility.

PMID- 26196537
TI  - Factors Associated with Time Since Last HIV Test Among Persons at High Risk for
      HIV Infection, National Survey of Family Growth, 2006-2010.
AB  - The Centers for Disease Control and Prevention (CDC) recommends annual HIV
      screening for persons at high risk for HIV infection. We assessed the testing
      history and factors associated with recent testing (tested in the last 12 months)
      among persons at high risk for HIV infection. We analyzed 2006-2010 National
      Survey of Family Growth data and classified respondents aged 15-44 who reported a
      sexual or drug-use risk behavior in the past year as 'high-risk'. Logistic
      regression models estimated prevalence ratios assessing the association between
      demographic and health-related factors and having been recently tested for HIV
      compared with never been tested. Among high-risk men, 29.3% had recently tested
      for HIV, 30.7% tested more than 12 months ago, and 40.0% had never been tested.
      Among high-risk women, 38.0% had recently tested, 36.9% tested more than 12
      months ago, and 26.1% had never been tested. Compared with men who were aged 15
      19, white, heterosexual, and had not recently visited a doctor, men who were aged
      40-44, black/African American, homosexual/gay or bisexual, and had visited a
      doctor in the past year were more likely to have recently tested. Compared with
      women who were white, had not recently visited a doctor, and had never been
      pregnant, women more likely to have recently tested were black/African American,
      had visited a doctor in the past year, and had been pregnant. Approximately two
      thirds of high-risk men and women had not been recently tested for HIV. CDC
      recommendations for annual screening are not being implemented for the majority
      of persons at risk. 

PMID- 26196538
TI  - Topical treatment in pain medicine: from ancient remedies to modern usage.
AB  - Over several millennia, substances have been applied to the skin for treatment of
      pain. Some ingredients are in current use; others have been discontinued.
      Mechanisms of action include interactions with nociceptive neural networks and
      inflammatory processes. Substances must penetrate the stratum corneum barrier and
      vehicles that enhance penetration have been developed. Topical drugs with links
      to the past include menthol, capsaicin, some opioids, local anesthetic agents and
      NSAIDs. Mandragora is also described as an example of a herbal remedy that has
      been discontinued due to its toxicity. The future for topical drugs is promising,
      with the advent of new drugs tailored for specific pain mechanisms and the
      development of both penetration enhancers and sterile preparation methods. 

PMID- 26196539
TI  - Activation of the GLP-1 Receptor by Liraglutide Increases ACE2 Expression,
      Reversing Right Ventricle Hypertrophy, and Improving the Production of SP-A and
      SP-B in the Lungs of Type 1 Diabetes Rats.
AB  - Diabetes alters microvascular function in the vascular beds of organs, including
      the lungs. Cardiovascular complications of pulmonary vascular affectation may be
      a consequence of the overactivation of the vasoconstrictive and proliferative
      components of the renin-angiotensin system. We previously reported that pulmonary
      physiology and surfactant production is improved by the glucagon-like peptide 1
      receptor (GLP-1R) agonist liraglutide (LIR) in a rat model of lung hypoplasia.
      Because we hypothesized that streptozotocin-induced diabetes rats would show
      deficiencies in lung function, including surfactant proteins, and develop an
      imbalance of the renin-angiotensin system in the lungs. This effect would in turn
      be prevented by long-acting agonists of the GLP-1R, such as LIR. The induction of
      diabetes reduced the surfactant protein A and B in the lungs and caused the
      vasoconstrictor component of the renin-angiotensin system to predominate, which
      in turn increased angiotensin II levels, and ultimately being associated with
      right ventricle hypertrophy. LIR restored surfactant protein levels and reversed
      the imbalance in the renin-angiotensin system in this type 1 diabetes mellitus
      rat model. Moreover, LIR provoked a strong increase in angiotensin-converting
      enzyme 2 expression in the lungs of both diabetic and control rats, and in the
      circulating angiotensin(1-7) in diabetic animals. These effects prompted complete
      reversion of right ventricle hypertrophy. The consequences of LIR administration
      were independent of glycemic control and of glucocorticoids, and they involved
      NK2 homeobox 1 signaling. This study demonstrates by first time that GLP-1R
      agonists, such as LIR, might improve the cardiopulmonary complications associated
      with diabetes. 

PMID- 26196540
TI  - Effects of Acupuncture, RU-486 on the Hypothalamic-Pituitary-Adrenal Axis in
      Chronically Stressed Adult Male Rats.
AB  - We have recently reported that pretreatment with electroacupuncture (EA) at
      stomach meridian point 36 (St36) prevents the chronic cold-stress increase in the
      hypothalamus-pituitary-adrenal axis (HPA), an action that may be under central
      control. Given that treatment for stress-related symptoms usually begins after
      onset of the stress responses, the objectives of the present study were to
      determine the efficacy of EA St36 on HPA hormones when EA St36 is given after
      stress was initiated, if the results are long lasting, and if blocking the
      glucocorticoid receptor (GR) using RU-486 had the same effects as EA St36. Adult
      male rats were placed in 4 groups of animals, 3 of which were exposed to cold and
      1 of which was a nontreatment control group. After exposure to the cold stress, 2
      groups were treated with either EA St36 or sham-EA, repeated over 10 days. The
      increase in ACTH and corticosterone observed in stress-only rats was prevented in
      EA St36 animals, and the effects remained intact 4 days after withdrawal of EA
      but continuation of cold stress. When the GR was blocked with RU-486, the
      efficacy of EA St36 remained unchanged. GR blockade did significantly elevate
      ACTH, which is not seen with EA St36, suggesting that EA St36 does act centrally.
      The elevated HPA hormones in stress-only rats were associated with a significant
      increase in depressive and anxious behavior; this was not observed in the
      stressed EA St36 animals. The results indicate that EA specifically at St36 vs
      sham-EA is effective in treating chronic poststress exposure. 

PMID- 26196541
TI  - Hyperleptinemia During Pregnancy Decreases Adult Weight of Offspring and Is
      Associated With Increased Offspring Locomotor Activity in Mice.
AB  - Pregnant women who are obese or have gestational diabetes mellitus have elevated
      leptin levels and their children have an increased risk for child and adult
      obesity. The goals of this study were to determine whether offspring weights are
      altered by maternal hyperleptinemia, and whether this occurs via behavioral
      changes that influence energy balance. We used 2 hyperleptinemic mouse models.
      The first was females heterozygous for a leptin receptor mutation (DB/+), which
      were severely hyperleptinemic, and that were compared with wild-type females. The
      second model was wild-type females infused with leptin (LEP), which were
      moderately hyperleptinemic, and were compared with wild-type females infused with
      saline (SAL). Total food consumption, food preference, locomotor activity,
      coordinated motor skills, and anxiety-like behaviors were assessed in wild-type
      offspring from each maternal group at 3 postnatal ages: 4-6, 11-13, and 19-21
      weeks. Half the offspring from each group were then placed on a high-fat diet,
      and behaviors were reassessed. Adult offspring from both groups of
      hyperleptinemic dams weighed less than their respective controls beginning at 23
      weeks of age, independent of diet or sex. Weight differences were not explained
      by food consumption or preference, because female offspring from hyperleptinemic
      dams tended to consume more food and had reduced preference for palatable, high
      fat and sugar, food compared with controls. Offspring from DB/+ dams were more
      active than offspring of controls, as were female offspring of LEP dams. Maternal
      hyperleptinemia during pregnancy did not predispose offspring to obesity, and in
      fact, reduced weight gain. 

PMID- 26196542
TI  - Impact of Reduced ATGL-Mediated Adipocyte Lipolysis on Obesity-Associated Insulin
      Resistance and Inflammation in Male Mice.
AB  - Emerging evidence suggests that impaired regulation of adipocyte lipolysis
      contributes to the proinflammatory immune cell infiltration of metabolic tissues
      in obesity, a process that is proposed to contribute to the development and
      exacerbation of insulin resistance. To test this hypothesis in vivo, we generated
      mice with adipocyte-specific deletion of adipose triglyceride lipase (ATGL), the
      rate-limiting enzyme catalyzing triacylglycerol hydrolysis. In contrast to
      previous models, adiponectin-driven Cre expression was used for targeted ATGL
      deletion. The resulting adipocyte-specific ATGL knockout (AAKO) mice were then
      characterized for metabolic and immune phenotypes. Lean and diet-induced obese
      AAKO mice had reduced adipocyte lipolysis, serum lipids, systemic lipid
      oxidation, and expression of peroxisome proliferator-activated receptor alpha
      target genes in adipose tissue (AT) and liver. These changes did not increase
      overall body weight or fat mass in AAKO mice by 24 weeks of age, in part due to
      reduced expression of genes involved in lipid uptake, synthesis, and
      adipogenesis. Systemic glucose and insulin tolerance were improved in AAKO mice,
      primarily due to enhanced hepatic insulin signaling, which was accompanied by
      marked reduction in diet-induced hepatic steatosis as well as hepatic immune cell
      infiltration and activation. In contrast, although adipocyte ATGL deletion
      reduced AT immune cell infiltration in response to an acute lipolytic stimulus,
      it was not sufficient to ameliorate, and may even exacerbate, chronic
      inflammatory changes that occur in AT in response to diet-induced obesity. 

PMID- 26196543
TI  - Characterization of Mycobacterium leprae Genotypes in China--Identification of a
      New Polymorphism C251T in the 16S rRNA Gene.
AB  - Leprosy continues to be prevalent in some mountainous regions of China, and
      genotypes of leprosy strains endemic to the country are not known. Mycobacterium
      lepromatosis is a new species that was discovered in Mexico in 2008, and it
      remains unclear whether this species exists in China. Here, we conducted PCR-
      restriction fragment length polymorphism (RFLP) analysis to classify genotypes of
      85 DNA samples collected from patients from 18 different provinces. All 171 DNA
      samples from skin biopsies of leprosy patients were tested for the presence of
      Mycobacterium leprae and Mycobacterium lepromatosis by amplifying the 16S rRNA
      gene using nested PCR, followed by DNA sequencing. The new species M.
      lepromatosis was not found among the 171 specimens from leprosy patients in 22
      provinces in China. However, we found three SNP genotypes among 85 leprosy
      patients. A mutation at C251T in the 16S rRNA gene was found in 76% of the
      strains. We also found that the strains that showed the 16S rRNA C251T mutation
      belonged to SNP type 3, whereas strains without the point mutation belonged to
      SNP type 1. The SNP type 3 leprosy strains were observed in patients from both
      the inner and coastal regions of China, but the SNP type 1 strains were focused
      only in the coastal region. This indicated that the SNP type 3 leprosy strains
      were more prevalent than the SNP type 1 strains in China. In addition, the 16S
      rRNA gene sequence mutation at C251T also indicated a difference in the
      geographical distribution of the strains. To our knowledge, this is the first
      report of a new polymorphism in 16S rRNA gene in M. leprae in China. Our findings
      shed light on the prevalent genotypes and provide insight about leprosy
      transmission that are important for leprosy control in China.

PMID- 26196544
TI  - Three-Dimensional LiMnPO4.Li3V2(PO4)3/C Nanocomposite as a Bicontinuous Cathode
      for High-Rate and Long-Life Lithium-Ion Batteries.
AB  - Olivine-type LiMnPO4 has been extensively studied as a high-energy density
      cathode material for lithium-ion batteries. To improve both the ionic and
      electronic conductivities of LiMnPO4, a series of carbon-decorated
      LiMnPO4.Li3V2(PO4)3 nanocomposites are synthesized by a facile sol-gel method
      combined with the conventional solid-state method. The optimized composite
      presents a three-dimensional hierarchical structure with active nanoparticles
      well-embedded in a conductive carbon matrix. The combination of the nanoscale
      carbon coating and the microscale carbon network could provide a more active site
      for electrochemical reaction, as well as a highly conductive network for both
      electron and lithium-ion transportation. When cycled at 20 C, an initial specific
      capacity of 103 mA h g(-1) can be obtained and the capacity retention reaches 68%
      after 3000 cycles, corresponding to a capacity fading of 0.013% per cycle. The
      stable capacity and excellent rate capability make this carbon-decorated
      LiMnPO4.Li3V2(PO4)3 nanocomposite a promising cathode for lithium-ion batteries. 

PMID- 26196546
TI  - Videogames: The Good, the Bad, and the Ugly.

PMID- 26196545
TI  - Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS)
      versus higher dose ICS for adults with asthma.
AB  - BACKGROUND: Long-acting muscarinic antagonists (LAMA), a class of drugs with
      proven effectiveness in chronic obstructive pulmonary disease (COPD), are being
      considered as an add-on option for adults with asthma whose condition is
      uncontrolled on inhaled corticosteroids (ICS). It is important to assess the
      safety and efficacy of LAMA add-on as an alternative to the prolonged use of
      higher doses of ICS, which are known to cause undesirable side effects in some
      people. OBJECTIVES: To compare the effects of adding a LAMA to any dose of ICS
      versus increasing the dose of ICS, for uncontrolled asthma in adults. SEARCH
      METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR) from
      its inception in 1995 to April 2015, imposing no restriction on language of
      publication. We also handsearched trial registries, reference lists of primary
      studies and existing reviews, as well as manufacturers' websites. SELECTION
      CRITERIA: We looked for parallel or cross-over randomised controlled trials
      lasting at least 12 weeks, in which adults whose asthma was not well controlled
      on ICS alone were randomised to treatment with LAMA add-on to ICS or with an
      increased dose of ICS. Trials were excluded if patients were taking long-acting
      beta2-agonists during the study period. DATA COLLECTION AND ANALYSIS: Two review
      authors independently screened the searches and extracted data from studies
      meeting all the inclusion criteria. We used Covidence to manage duplicate
      screening, data extraction and risk of bias judgements, and to form a consensus
      where discrepancies arose. We used standard methods expected by The Cochrane
      Collaboration.The pre-specified primary outcomes were exacerbations requiring a
      course of oral corticosteroids (OCS), effects on quality of life and serious
      adverse events. MAIN RESULTS: One cross-over randomised controlled trial met the
      inclusion criteria. The trial was performed in 210 patients with moderate to
      severe asthma and compared the use of the LAMA tiotropium bromide with double
      dose beclomethasone (an ICS) using a cross-over design and 14-week treatment
      periods.Compared with people taking a double dose of ICS, fewer people taking a
      LAMA add-on had an exacerbation requiring treatment with OCS (odds ratio (OR)
      0.57, 95% confidence interval (CI) 0.22 to 1.43) or an exacerbation resulting in
      emergency department admission (OR 0.49, 95% CI 0.09 to 2.77), but the confidence
      intervals for both outcomes did not exclude the possibility that double dose ICS
      was more effective. Serious adverse events and exacerbations requiring
      hospitalisation occurred in similarly low numbers of people taking each
      treatment, but confidence intervals were too wide to suggest that the two
      treatment options were equivalent.Asthma-related quality of life was similar in
      both treatment groups (mean difference (MD) in change from baseline 0.10, 95% CI 
      0.07 to 0.27). Those taking LAMA add-on scored slightly better on a scale
      measuring asthma control than those increasing their ICS dose (MD in change from
      baseline - 0.18, 95% CI - 0.34 to - 0.02), although the difference was clinically
      small. Evidence was deemed low quality for both quality of life and asthma
      control.There was moderate-quality evidence that participants' trough forced
      expiratory volume in one second (FEV1) was 100 mL better when taking LAMA add-on
      than with increased ICS dose (MD in change from baseline 0.10, 95% CI 0.03 to
      0.17). AUTHORS' CONCLUSIONS: Only one randomised trial was found, comparing
      tiotropium add-on to increased dose beclomethasone. Differences between the
      treatments were too small or imprecise to understand whether adding a LAMA to ICS
      is safer or more effective than increasing the dose of ICS, and there is a
      possibility of carry-over effects due to the study's cross-over design. LAMA add
      on may lead to more improvement in lung function (FEV1) than an increased dose of
      ICS.The results of this review, alongside pending results from related reviews
      assessing the use of LAMA against other treatments, will help to define the role
      of these drugs in asthma management, and this review should be updated as results
      from future trials emerge. Studies assessing the role of LAMA add-on should be
      longer and include a double-ICS treatment arm so that the results can be
      interpreted in the context of the guideline-recommended treatment options that
      are available to physicians.

PMID- 26196547
TI  - [Not Available].

PMID- 26196549
TI  - Funding for Health Games Research After the Robert Wood Johnson Foundation
      Pioneer Portfolio.

PMID- 26196548
TI  - Eden Institute: Using Health Games for ASD Student and Staff Development.
AB  - Eden Autism Services is a leading-edge resource for children and adults suffering
      from more severe effects of autism spectrum disorder (ASD). The strategic use of
      games in the development of students, staff, teachers, parents, friends, and
      employers has advanced the quality of life of Eden's students and, consequently,
      their relationships, productivity, and happiness. 

PMID- 26196550
TI  - A New Program for Healthy Eating Study Using a Card Game.
AB  - OBJECTIVE: A new program using a card game for study of children's food risk
      communication was developed to meet the needs of learning healthy eating. To
      examine the effects of the new program, an experiment was carried out in an
      elementary school with 132 students. MATERIALS AND METHODS: The game rules
      resemble those of common card games. Keeping seven cards in their hands, players
      exchange one of their cards for another card from the card stack to make a set of
      food they usually eat. Through the process, they can learn other players' dietary
      lives. The effects of the card game program and the control program were
      evaluated by a questionnaire study. RESULTS: Scores for three characteristics
      enjoyment, satisfaction, and communication with the other players-for the new
      program showed higher average values compared with the conventional program
      without the game. CONCLUSIONS: The findings indicate that the newly developed
      program is beneficial for children's learning healthy eating.

PMID- 26196551
TI  - Computer Games as Therapy for Persons with Stroke.
AB  - BACKGROUND: Stroke affects approximately 800,000 individuals each year, with 65%
      having residual impairments. Studies have demonstrated that mass practice leads
      to regaining motor function in affected extremities; however, traditional therapy
      does not include the repetitions needed for this recovery. Videogames have been
      shown to be good motivators to complete repetitions. Advances in technology and
      low-cost hardware bring new opportunities to use computer games during stroke
      therapy. This study examined the use of the Microsoft (Redmond, WA) KinectTM and
      Flexible Action and Articulated Skeleton Toolkit (FAAST) software as a therapy
      tool to play existing free computer games on the Internet. SUBJECTS AND METHODS:
      Three participants attended a 1-hour session where they played two games with
      upper extremity movements as game controls. Video was taken for analysis of
      movement repetitions, and questions were answered about participant history and
      their perceptions of the games. RESULTS: Participants remained engaged through
      both games; regardless of previous computer use all participants successfully
      played two games. Five minutes of game play averaged 34 repetitions of the
      affected extremity. The Intrinsic Motivation Inventory showed a high level of
      satisfaction in two of the three participants. CONCLUSIONS: The Kinect Sensor
      with the FAAST software has the potential to be an economical tool to be used
      alongside traditional therapy to increase the number of repetitions completed in
      a motivating and engaging way for clients.

PMID- 26196552
TI  - Developing Home-Based Virtual Reality Therapy Interventions.
AB  - OBJECTIVE: Stroke is one of the leading causes of serious long-term disability.
      However, home exercise programs given at rehabilitation often lack in
      motivational aspects. The purposes of this pilot study were (1) create
      individualized virtual reality (VR) games and (2) determine the effectiveness of
      VR games for improving movement in upper extremities in a 6-week home therapy
      intervention for persons with stroke. SUBJECTS AND METHODS: Participants were two
      individuals with upper extremity hemiparesis following a stroke. VR games were
      created using the Looking Glass programming language and modified based on
      personal interests, goals, and abilities. Participants were asked to play 1 hour
      each day for 6 weeks. Assessments measured upper extremity movement (range of
      motion and Action Research Arm Test [ARAT]) and performance in functional skills
      (Canadian Occupational Performance Measure [COPM] and Motor Activity Log [MAL]).
      RESULTS: Three VR games were created by a supervised occupational therapist
      student. The participants played approximately four to six times a week and
      performed over 100 repetitions of movements each day. Participants showed
      improvement in upper extremity movement and participation in functional tasks
      based on results from the COPM, ARAT, and MAL. CONCLUSIONS: Further development
      in the programming environment is needed to be plausible in a rehabilitation
      setting. Suggestions include graded-level support and continuation of creating a
      natural programming language, which will increase the ability to use the program
      in a rehabilitation setting. However, the VR games were shown to be effective as
      a home therapy intervention for persons with stroke. VR has the potential to
      advance therapy services by creating a more motivating home-based therapy
      service.

PMID- 26196553
TI  - Machinima and Video-Based Soft-Skills Training for Frontline Healthcare Workers.
AB  - Multimedia training methods have traditionally relied heavily on video-based
      technologies, and significant research has shown these to be very effective
      training tools. However, production of video is time and resource intensive.
      Machinima technologies are based on videogaming technology. Machinima technology
      allows videogame technology to be manipulated into unique scenarios based on
      entertainment or training and practice applications. Machinima is the converting
      of these unique scenarios into video vignettes that tell a story. These vignettes
      can be interconnected with branching points in much the same way that education
      videos are interconnected as vignettes between decision points. This study
      addressed the effectiveness of machinima-based soft-skills education using avatar
      actors versus the traditional video teaching application using human actors in
      the training of frontline healthcare workers. This research also investigated the
      difference between presence reactions when using avatar actor-produced video
      vignettes as compared with human actor-produced video vignettes. Results
      indicated that the difference in training and/or practice effectiveness is
      statistically insignificant for presence, interactivity, quality, and the skill
      of assertiveness. The skill of active listening presented a mixed result
      indicating the need for careful attention to detail in situations where body
      language and facial expressions are critical to communication. This study
      demonstrates that a significant opportunity exists for the exploitation of avatar
      actors in video-based instruction. 

PMID- 26196554
TI  - "Braingame Brian": Toward an Executive Function Training Program with Game
      Elements for Children with ADHD and Cognitive Control Problems.
AB  - In the area of childhood attention-deficit hyperactivity disorder, there is an
      urgent need for new, innovative, and child-focused treatments. A computerized
      executive functioning training with game elements aimed at enhancing self-control
      was developed. The first results are promising, and the next steps involve
      replication with larger samples, evaluating transfer of training effects to daily
      life, and enhancing motivation through more gaming elements. 

PMID- 26196555
TI  - Self-Presence and the Effects of the Avatar on Health and Appearance.
AB  - Self-presence, defined as the degree of connectedness with one's avatar as well
      as the effects of the avatar on perceptions of oneself, suggests that
      interactions with an avatar may have real implications for how one perceives and
      treats the body offline. A study examining the influence of the "Second Life"
      avatar on "Second Life" users' offline appearance, health, and well-being is
      discussed, along with the importance of examining self-presence as a theoretical
      mechanism. This research engages with the idea that immersion with an avatar via
      social virtual play has an influence on our health offline. 

PMID- 26196557
TI  - [Not Available].

PMID- 26196556
TI  - "RAGE-Control": A Game to Build Emotional Strength.
AB  - Emotional regulation is an important skill, and some children require extra
      support to develop that skill. To address this need, we have built an active
      biofeedback videogame and incorporated the game into a cognitive behavioral
      therapy. Our approach requires that players simultaneously attend to a demanding
      task and still maintain emotional control, forcing practice and skill building in
      both domains concurrently. Early studies have shown that our approach improves
      emotional control compared with treatment as usual and has led to promising new
      developments of emotionally aware toys that can reach younger children. 

PMID- 26196558
TI  - Profile of children with new-born brachial plexus palsy managed in a tertiary
      hospital in Ibadan, Nigeria.
AB  - New-born Brachial Plexus Palsy (NBPP) is birth injury resulting from traction to
      the brachial plexus at birth. It is an injury to two or more cervical or thoracic
      nerve roots. It has been reported to be one of the most common birth injuries of
      the new-born. Persistent presentation of children with NBPP in Nigeria paediatric
      practice necessitates the need to examine prevalence, patterns and possible
      predisposing factors. This study therefore investigated retrospectively, profiles
      of children who presented with NBPP over a ten year period and were managed at
      the Physiotherapy department of the University College Hospital, Ibadan Nigeria.
      A retrospective cross-sectional survey, in which files of children with NBPP
      located from the database of the Physiotherapy department were retrieved in order
      to assess infant and maternal information. One hundred and seventy children, 93
      (54.7%) males and 77 (45.3%) females were studied. Their mean birth weight was
      4.21+/-0.54 kg, 99 (58.2%) were delivered in private (non-government) hospitals,
      majority 163 (95.9%) presented with Erb's Palsy. Mothers, 54 (31.8%) were mostly
      primiparous and a seemingly persistent elevation in two-yearly incidence of NBPP
      was observed. Improved healthcare policy in child delivery is encouraged in non
      government hospitals in Nigeria to provide preventive measures toward incidence
      of NBPP. Documentation of physiotherapy management of children with NBPP should
      include outcomes from admission through to discharge. 

PMID- 26196559
TI  - Vascular Effects of Histamine.
AB  - Four subtypes of receptors (H1, H2, H3 and H4) mediate the actions of histamine.
      In the vascular wall, the effects of histamine are mediated via H1 and H2
      receptors and the actions are modulated by H3 receptor subtype located on
      presynaptic neurones. Alterations in vascular responses to histamine are
      associated with experimental as well as a human form of hypertension, suggesting
      a role for histanine in cardiovascular regulation. 

PMID- 26196560
TI  - Effect of zinc treatment on intestinal motility in experimentally induced
      diarrhea in rats.
AB  - Zinc supplementation is a critical new intervention for treating diarrheal
      episodes in children. Recent studies suggest that administration of zinc along
      with new low osmolarity oral rehydration solutions / salts (ORS) can reduce the
      duration and severity of diarrheal episodes for up to three months. Several
      mechanisms of action of zinc has been proposed, however there is dearth of
      information about the effect of zinc on intestinal motility during diarrhea. Male
      albino Wistar rats (80-100g) were used. The effect of different doses of zinc
      sulphate (25, 50, 100, 150 mg/Kg) on the number of wet faeces was investigated.
      Intestinal motility during castor oil induced diarrhea was assessed using
      activated charcoal meal and the mechanisms of action of zinc sulphate on motility
      were investigated. The effective dose of zinc sulphate (100mg/Kg) significantly
      reduced (p< 0.001) the number of wet faeces (3.0 +/- 0.00) compared with control
      (6.8 +/- 0.25) during diarrhea. This antidiarrheal effect of zinc was abolished
      by propranolol and nifedipine. Zinc sulphate significantly reduced (p< 0.05)
      intestinal transit time (60.7 +/- 7.13%) compared with control (85.7 +/- 2.35%).
      It is concluded that zinc sulphate reduces the frequency of wet faeces output and
      intestinal motility during diarrhea via activation of beta adrenergic receptor
      and L-type Ca2+ channel.

PMID- 26196562
TI  - Intestinal glucose uptake responses to infusion of glucose, fructose and
      galactose in dogs Intestinal glucose uptake responses to infusion of glucose,
      fructose and galactose in dogs.
AB  - The present study was designed to investigate the effects of intravanous (i.v)
      infusion of fructose, galactose and glucose on canine IGU during postprandial
      state. Experiments were carried out on fasted, male, anaesthethized adult mongrel
      dogs divided into four groups with 5 dogs per group. Each of the groups was given
      i.v infusion of normal saline, fructose (0.15, 0.55 and 1.1mg/dl/min), galactose
      (0.15, 0.55 and 1.1mg/dl/min) and glucose (0.15, 0.55 and 1.1mg/dl/min)
      respectively. Through a midline laparatomy, the upper jejunum was secured and
      cannulated for blood flow measurement. Blood samples were obtained for
      measurement of glucose content of arterial and venous blood from the upper
      jejunal segment. The blood glucose was determined by glucose oxidase method and
      intestinal glucose uptake was calculated as the product of jejunal blood flow and
      arterio-venous glucose difference. Values are means +/- S.E.M, compared by ANOVA
      and Student t-test. Fructose, galactose and glucose significantly increased
      arterial blood glucose from 97.60 +/- 1.78 mg/dl to 114.20 +/- 1.88, 109.80 +/-
      1.43, and 141.20 +/- 5.65 mg/dl, respectively. Glucose also significantly
      increased jejunal blood flow from 10.0 +/- 0.32 ml/min to 14.40 +/- 0.93 ml/min,
      however, fructose and galactose did not produce any significant effect on
      intestinal blood flow. IGU increased by 600%, 350%, and 700% in response to
      fructose, galactose and glucose respectively. There is no correlation between the
      increase in blood glucose levels induced by each of the sugars and its
      corresponding rise in IGU. The data suggest that the intestine responds to
      fructose and galactose in a similar manner as glucose probably through similar
      mechanism.

PMID- 26196561
TI  - Gender and environmental influences on visual acuity in Owerri, Nigeria.
AB  - This study assessed the gender and environmental influences on visual function
      among adults in Owerri, Nigeria. Visual acuity (V.A.) is a measure of visual
      function in health and disease. Visual disability together with other disabling
      conditions is a barrier to development, yet there is little known about the
      visual acuity and determinants of visual function in Owerri, Imo State, Nigeria.
      Results of a cross-sectional analytical study conducted between September 2007
      and November 2009 using 3451 adults living in Owerri, Nigeria consisting of 2606
      persons (test) and 845 persons( control), randomly selected are presented. Data
      were obtained using interviewer administered structured - questionnaires and
      standard procedures were used to determine gender and environmental influences on
      visual acuity. There were more females with poor vision than males in both study
      and control groups. The majority of the subjects were aged 40-49. At 6 metres,
      20.9% and 39.1% of study and control groups in the right eye; 31.8% and 41.2% of
      study control groups respectively in the left eye had unaided V.A. >= 6/6.
      Similarly at 6m, 18.0% and 4.3% of study and control groups in the right eye;
      15.2% and 5.0% of study and control groups respectively in the left eye had
      unaided V.A. < 6/18. Twenty-nine per cent and 25.0% of study and control groups
      respectively had unaided V.A. at near of N5. Over 70.0% had <= N6 at near and
      V.A. improvement with pin-hole device. Emmetropia was found in 20.5% (study) and
      23.2% (control). The percentage prevalence of reduced VA was higher among
      ametropics and rural dwellers. The contributory factors were poor nutrition &
      irrational and uncontrolled use of chloroquine as first line drug for malaria
      treatment. Health education on diet, drug use and safe environmental health
      practices especially for persons living in rural areas in developing countries
      are recommended.

PMID- 26196563
TI  - Hepatoprotective and anticlastogenic effects of ethanol extract of Irvingia
      gabonensis (IG) leaves in sodium arsenite-induced toxicity in male Wistar rats.
AB  - Consumption of arsenic contaminated water has been associated with diverse health
      defects such as cancer and skin lesions. Some plants of medicinal value have been
      reported to show protective effects against toxins. In this study, the effects of
      ethanol extract of the leaves of Irvingia gabonensis (IG) against sodium arsenite
      (SA) induced hepatotoxicity and clastogenicity in male Wistar rats was
      investigated. Eight groups of five rats each were used for the study. They were
      administered with 250 or 500 mg/kg body weight of IG with or without SA at 2.5
      mg/kg body weight. IG extract has a significant (p<0.05) reducing effect on serum
      liver function enzymes, aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and gamma glutamyltransferase (gammaGT) activities. This
      was corroborated with the histopathological analysis findings. Also the groups
      treated with both the extract and SA recorded significantly (p<0.05) reduced
      number of micronuclei when compared with the group treated with SA only. IG
      extract also reduced the oxidative stress induced by SA as measured by the
      reduced generation of hydrogen peroxide (H2O2) and significant (p<0.05)
      difference in the CAT and SOD activities between the groups treated with both SA
      and extract, and the positive control group administered SA alone. This study
      therefore shows that the ethanol leaf extract of Irvingia gabonensis have
      hepatoprotective and anticlastogenic effects against sodium arsenite-induced
      toxicity possibly by enhancing the antioxidant status in the Wistar rats.

PMID- 26196564
TI  - The role of oropharnygeal receptors in thirst perception after dehydration and
      rehydration.
AB  - This study examined the effect of drinking and gargling on thirst perception (TP)
      in 33 young dehydrated female subjects (18-25 yrs), using the visual analogue
      scale (VAS). Group A subjects drank, while group B gargled the fluid provided -
      0.0%, 0.9% and 1.8% NaCl (7.0 ml/kg body weight of fluid). The procedure was
      alternated two weeks later. All subjects dehydrated for 18 hours prior to the
      study, and the last 12-hour urine was collected and volume recorded. Subject who
      provided a 12 hr urine volume greater than 400 ml was excluded from the study.
      After recording the baseline TP, and voiding the bladder, drinking/gargling was
      done within 5 minutes, and the subsequent TPs were recorded at 5 minutes interval
      for 25 minutes. Blood samples were collected before and at the end of the 30
      minutes, when urine volumes were recorded. Drinking (0.0% and 1.8% NaCl) resulted
      in an initial decrease in thirst perception, which was statistically significant
      (p<0.05) only up to 10 minutes. Water intake ad libitum (mean +/- SEM) at the end
      of the 30 minutes was statistically significantly lower (p<0.05) only in the
      group that drank 0.0% NaCl. Gargling on the other hand did not affect TP and
      water intake throughout the period of study. It can be concluded that drinking,
      but not gargling reduces thirst perception irrespective of the tonicity of the
      fluid as earlier reported (Obika et. al., 2009; Salata et. al., 1987). This study
      suggests that the oropharyngeal receptors for TP are activated by recurrent
      stimulation by the act of drinking rather than gargling.

PMID- 26196565
TI  - Histological changes in the cerebelli of adult wistar rats exposed to cigarette
      smoke.
AB  - The different constituents of tobacco smoke have been linked to different
      diseased conditions. In this work, the histological effects of cigarette smoke on
      the cerebellum of adult male Wistar rats were studied. Sixteen Wistar rats with
      mean weight of 153.24 +/- 4.12 g were grouped equally into four. The Control
      Group A was exposed to fresh air, while Groups B, C and D animals were each
      exposed to smoke from one, two and three sticks of cigarette respectively. Each
      stick of cigarette was completely consumed within an average duration of 11
      minutes. Improvised smoking chambers were constructed and used for the exposure
      daily, while treatment lasted for 28 days. The animals were thereafter sacrificed
      by cervical dislocation, the cranium was exposed and the brain gently removed and
      weighed; the cerebellum was excised, weighed, and fixed in formol calcium, and
      subsequently processed for histological observation using the Haematoxylin and
      Eosin staining principle. Loss of weight and reduction in weight gain were
      noticed in the treatment groups, with corresponding reduction in cerebellar
      weights, in a dose-dependent pattern. Histology also revealed loss of white
      matter, reduction in thickness of cell layers and their cellular components.
      Increasing dosage of cigarette smoke could predispose to progressive compromise
      in the structural integrity and composition of the cerebellum, and this might
      result in cerebellar dysfunction. 

PMID- 26196566
TI  - Bioinformatic analysis of dihydrofolate reductase predicted in the genome
      sequence of Lactobacillus pentosus KCA1.
AB  - Physiologic studies of Lactobacillus species show that some species cannot
      synthesize folate de novo, which is required for growth. Folate plays a critical
      role in regulating the amount of tetrahydrofolate in the cell that is utilized
      for DNA replication, and proliferation of the erythropoietic system. We recently
      sequenced the genome of Lactobacillus pentosus KCA1, isolated from a Nigerian
      subject. The genome has open reading frames coding for the complete genes
      required for folate biosynthesis. Our previous study shows that rats fed with L.
      pentosus KCA1 led to enhancement of haematological parameters. Bioinformatic tool
      such as ClustalW algorithm was used to analyze dihydrofolate reductase
      (folA/dfrA) encoded in the genome sequence of L. pentosus KCA1 for comparative
      multiple sequence alignments. I-TASSER was used to predict the 3-D model
      structure of the protein and potential active binding site residues. Result show
      that two unique amino acid substitutions were found in KCA1_1610 sequence at
      position 85 with alanine (A-Ala85), while other strains have aspartic acid (D
      Asp) for other L. pentosus and threonine (T-Thr) for L. plantarum strains at the
      same position. The result suggests that dihydrofolate reductase can be used as a
      distinguishing marker between L. pentosus KCA1 and other pentosus including L.
      plantarum strains. The secondary structure prediction with I-TASSER revealed 5
      alpha helices and 8 beta-strands. Twelve binding site residues were predicted in
      KCA1_1610 relative to the template protein 2zzaA in protein database (PDB). The
      predicted structure of KCA1_1610 dihydrofolate reductase can serve as a new
      template as an addition to structural genomics and generation of models for use
      in drug screening and physiological function inference.

PMID- 26196567
TI  - Comparative evaluation of the sperm characteristics and morphology of adult
      Wistar rats fed either low or normal protein-energy diets and orally dosed with
      aqueous Cuscuta australis extracts.
AB  - Cuscuta australis (C. australis) seed and stem are commonly used as dietary
      supplements in a maize-meal, "Ogi", by the local population for the management of
      male and female reproductive dysfunctions. This study, as a part of on-going
      efforts, therefore, evaluated and compared the effects of Low Protein-energy (LP)
      and Normal Protein-energy (NP) diets on the sperm morphology and characteristics
      of adult Wistar rats orally dosed aqueous extracts of C. australis seed (LPSE and
      NPSE) and stem (LPST and NPST), 300 mg of extract/kg body weight of rat/day, for
      seven days. The control groups (LPWA and NPWA) received vehicle, water. Live-dead
      ratio and percentage of sperms with curved tail were significantly decreased
      (p<0.01) in the NPST relative to the NPWA, LPWA, LPST, NPSE and LPSE. Total
      abnormal sperm counts, acephalic sperms and tailless head sperms were
      significantly decreased (p<0.001, p<0.05 and p<0.001, respectively) in the LPST
      and NPST relative to LPSE, NPSE, LPWA and NPWA. The LPSE, LPST and NPST showed
      significantly decreased (p<0.05) percentages of sperms with either bent mid-piece
      or curved mid-piece relative to the LPWA. Significantly decreased (p<0.05)
      percentage of sperms with curved mid-piece was also observed in the NPSE relative
      to LPWA. Protein-energy diet significantly influenced (at least p<0.05) the
      effect of each extract on sperm motility and percentage of sperms with curved
      tail. Stem extract significantly decreased (p<0.01) the percentages of acephalic
      sperms and tailless head sperms. Diet-stem extract interaction significantly
      influenced (p<0.05) live-dead ratio. Our data suggest that orally administered
      aqueous extracts of C. australis generally enhanced the sperm morphology and
      characteristics of the male Wistar rat and that the stem extract maintained sperm
      morphology better than the seed extract. It also showed that the stem extract
      decreased live-dead ratio and that the efficacy of orally administered aqueous C.
      australis stem extract may be affected by variations in dietary protein-energy
      levels.

PMID- 26196568
TI  - Normal Limits of Electrocardiogram and Cut-Off Values for Left Ventricular
      Hypertrophy in Young Adult Nigerians.
AB  - This study assessed healthy young adults to determine the normal limits for
      electrocardiographic variables and cut-off values for left ventricular
      hypertrophy. It was a cross sectional descriptive study in which the participants
      were evaluated clinically by standard 12-lead resting electrocardiogram (ECG) at
      25 mm/s during quiet respiration. The heart rate, P wave duration, axis and
      amplitude, PR and QT intervals, QRS duration, axis and amplitude and T wave axis
      were assessed. Three hundred and twenty four (324) volunteers comprising of 175
      males and 149 females aged 20 to 30 years (mean, 23.01 +/- 2.88 years)
      participated in the study. The normal limits for heart rate, P wave duration,
      amplitude and axis in lead II, QRS duration and axis, T wave axis, PR interval,
      QT interval and QTc respectively were; 61-93 beats per minute,0.08-0.12s,1.00
      2.00 mm,22.00-79.000,78.00-106.00 ms,15.50-81.000, 24.25-69.000,0.12-0.19s, 0.32
      0.40s and 0.36-0.44s. The cut-off values for Sokolow-Lyon, Cornell and Araoye
      criteria for assessment of left ventricular hypertrophy (LVH) were higher than
      those previously in use in medical practice. Gender difference exists in some cut
      off values for LVH. This study defined the normal limits for electrocardiographic
      variables for young adult Nigerians. Racial factor should be taken into
      consideration in interpretation of ECG.

PMID- 26196569
TI  - Analgesic activity of the ethanol extract of Curcuma longa rhizome and its
      mechanism of action.
AB  - This study examined the antinociceptive activity and mechanism of action of the
      ethanol extract of Curcuma longa rhizome using animal models of thermal (tail
      flick and hot plate) and chemical (acetic acid writhing and formalin) tests of
      nociception. The mechanism of action was investigated using adrenergic and opioid
      receptor blockers. The extract (50-150 mg/kg) given intraperitoneally (i.p) 30
      minutes to the test produced a dose dependent inhibition of both the acetic acid
      induced writhing and formalin licking in the chemical tests. In the thermal
      tests, the extract produced a prolongation of both the hot plate and tail
      withdrawal latencies. Prior administration of both the adrenergic receptor
      antagonists (prazosin and propranolol) and opioid receptor blocker (naloxone) did
      not produce any significant changes in these observations. These result showed
      that the antinociceptive activity of Curcuma longa is non-adrenergic and non
      opioid dependent. 

PMID- 26196570
TI  - Glucose utilization and anti-oxidative mechanisms of the aqueous hunteria
      umbellata seed extract in alloxan-induced diabetic rats.
AB  - In South-west Nigeria, water decoctions of Hunteria umbellata seeds are highly
      valued by traditional healers in the local management of diabetes mellitus,
      obesity and hyperlipidemia. Previous studies hypothesized one of the
      antihyperglycemic mechanisms of the aqueous seed extract of Hunteria umbellata
      (HU) to be mediated probably via increased peripheral glucose utilization. The
      present study, therefore, was designed at evaluating the peripheral glucose
      utilization and anti-oxidative mechanisms of 50 mg/kg, 100 mg/kg and 200 mg/kg of
      HU in alloxan-induced diabetic rats in Groups IV-VI rats as well as in the
      control groups (Groups I-III). Experimental type 1 DM was induced in male Wistar
      rats through intraperitoneal injection of 150 mg/kg of alloxan monohydrate in
      cold 0.9% normal saline after which the diabetic rats were orally treated with 50
      200 mg/kg of HU for 14 days. Effects of HU on the rat body weight, percentage
      body weight changes and fasting blood glucose (FBG) were determined on days 1 and
      15 of the experiment. Also, on day 15 of the experiment, HU effect on serum
      insulin, liver enzyme markers, proteins, albumin, triglyceride, total cholesterol
      and lactate dehydrogenase as well as on hepatic tissue oxidative stress markers,
      liver glycogen and glucose-6-phosphatase were determined after sacrificing the
      rats under diethyl ether anesthesia. Results showed that oral treatments with 50
      200 mg/kg of HU caused significant (p<0.0001) improvements in the weight loss
      caused by alloxan-induced diabetes, while causing significant (p<0.05, p<0.001
      and p<0.0001) dose-related reductions in the FBG levels despite causing non
      significant (p>0.05) alterations in the serum INS levels in the treated rats.
      Also, repeated oral treatment with HU caused significant (p<0.0001) reversal in
      the decrease and increase in the hepatic glycogen levels and glucose-6
      phosphatase activity, respectively, caused by alloxan-induced diabetes. Similar
      significant (p<0.0001) and complete reversal effects were recorded in the serum
      hepatic enzyme markers, total protein, albumin, triglyceride, total cholesterol
      and lactate dehydrogenase as well as on hepatic tissue oxidative stress markers
      such as superoxidase dismutase (SOD), catalase (CAT), malonialdehyde (MDA) and
      reduced glutathione (GSH) of HU-treated rats when compared to that of untreated
      alloxan-induced diabetic rats. In conclusion, results of this study showed HU
      treatment to significantly ameliorate the hyperglycemia and oxidative stress in
      alloxan-induced diabetic rats which was mediated via increased hepatic glycogen
      deposit, decreased hepatic glucose-6-phosphatase activity and improvement in
      antioxidant/free radicals scavenging activities.

PMID- 26196571
TI  - Intestinal Ischaemia-Reperfusion Injury and Semen Characteristics in West African
      Dwarf Bucks.
AB  - Increasing production of goats takes their reproductive potential and fertility,
      into consideration. Gastrointestinal obstructive lesions can set up an intestinal
      ischaemia-reperfusion. Testicular torsion is an established cause of testicular
      damage and infertility and is a form of ischaemia-reperfusion injury. This study
      investigates the effect of intestinal ischaemia-reperfusion (IIR) injury on semen
      characteristics in WAD bucks. Six healthy adult male WAD goats were divided into
      two groups of three, a control and IIR group, one hour ischaemia and two hours of
      reperfusion were achieved in the intestinal ischaemia-reperfusion (IIR) group
      after all goats underwent a laparotomy. Semen collection was done using the
      electro-ejaculator method pre-operatively and weekly for four weeks post
      operatively. The semen concentration, percentage of normal sperm cells, abnormal
      sperm cells and percentage abnormality were evaluated. In control animals, there
      was an increase in semen concentration postoperatively followed by a decrease
      whereas in IIR animals, a decrease was observed postoperatively till the 4th
      week. Total normal sperm cells decreased postoperatively and then increased to
      preoperative levels whereas a decrease was seen in IIR animals till the 3rd
      postoperative week. Abnormalities in sperm cells, normal head without tail,
      normal tail without head, bent mid-piece, curved mid-piece and rudimentary tail
      were all increased by the 4th week in IIR group though the total number of
      abnormal cells was observed to have decreased. The main effect of intestinal
      ischaemic-reperfusion injury on the semen characteristics of WAD goats is an
      increase in abnormalities with an adequate quantity of semen. Many of the
      abnormalities involved midpiece and tail abnormalities which are very vital to
      propulsion and may cause an inability of the sperm cells to fertilize. This
      hitherto silent phenomenon in farm animals may be the reason for iatrogenic
      causes of infertility. 

PMID- 26196572
TI  - Role of Adrenergic Receptors in Glucose, Fructose and Galactose-Induced Increases
      in Intestinal Glucose Uptake in Dogs.
AB  - The study investigated the role of adrenergic receptors in glucose, fructose-,
      and galactose- induced increases in intestinal glucose uptake. Experiments were
      carried out on fasted male anaesthetized Nigerian local dogs divided into seven
      groups (with five dogs per group). Group I dogs were administered normal saline
      and served as control. Dogs in groups II, III and IV were intravenously infused
      with glucose (1.1 mg/kg/min), fructose (1.1 mg/kg/min) and galactose (1.1
      mg/kg/min) respectively. Another three groups, V, VI and VII were pretreated with
      prazosin (0.2mg/kg), propranolol (0.5mg/kg) or a combination of prazosin
      (0.2mg/kg) and propranolol (0.5mg/kg) followed by glucose infusion, frutose
      infusion or galactose infusion respectively. Through a midline laparatomy, the
      upper jejunum was cannulated for blood flow measurement and blood samples were
      obtained for measurement of glucose content of the arterial blood and venous
      blood from the upper jejunal segment. Glucose uptake was calculated as the
      product of jejunal blood flow and the difference between arterial and venous
      glucose levels (A-V glucose). The results showed that pretreatment of the animal
      with prazosin had no effect on glucose and galactose induced increases in glucose
      uptake. However, pretreatment with propranolol completely abolished glucose,
      fructose and galactose-induced increases in intestinal glucose uptake. Prazosin
      also significantly reduced galactose-induced increase in intestinal glucose
      uptake. The results suggest that the increases in intestinal glucose uptake
      induced by glucose and fructose are mediated mostly by beta adrenergic receptors
      while that of galactose is mediated by both alpha and beta adrenergic receptors. 

PMID- 26196573
TI  - In Vitro Antioxidant Properties of Methanolic Leaf Extract of Vernonia Amygdalina
      Del.
AB  - Various methods employed in evaluating antioxidant activities of various samples
      gives varying results depending on the specificity of the free radical or oxidant
      used as a reactant. This study investigated the antioxidant /radical scavenging
      properties of the methanolic extract of Vernonia amygdalina (MEVA) leaves and
      studied the relationship between the assay methods. Antioxidant capacity of MEVA
      was evaluated by measuring the radical scavenging activity (RSA) of MEVA on 1,1
      diphenyl-2-picrylhydrazyl radical (DPPH*), nitric oxide (NO) and hydrogen
      peroxide (HP), hydroxyl radical (OH*) scavenging activity (HRSA), lipid
      peroxidation inhibition activity (LPIA) against 2,2,-azobis(2-amidinopropane)
      hydrochloride (AAPH) and Trolox Equivalent Antioxidant Capacity (TEAC) of MEVA
      against 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt
      (ABTS+) radicals as well as the reducing power (RP). Assay methods were subjected
      to regression analysis and their correlation coefficients calculated. Results
      were analysed using student"s t-test and ANOVA. MEVA exhibited highest percentage
      RSA of 85.8% on HP, followed by DPPH* (29.6%), OH* (26.4%) and least on NO*
      (21.8%). MEVA inhibited AAPH-induced lipid peroxidation by 30.0% and ABTS-induced
      radical by 1489% with a marked RP of 0.242+/-0.01. DPPH correlated excellently
      with RP (r2 = 0.86), TEAC (r2 = 0.94) and HRSA (r2 = 0.89), the four having good
      relationship with each other, while LPIA correlated moderately with HP (r2 = 0.48
      and NO (r2 = 0.34). MEVA exhibited significant free radical scavenging and
      antioxidant activities. The assay methods correlates very well and could
      therefore be employed for investigating and understanding antioxidant properties
      and scavenging activities of plant materials. 

PMID- 26196574
TI  - Comparison of Outcome of Students' Performance Using the Standard Setting Method
      with the Absolute Grading Method in Preclinical Examination.
AB  - This study compared the outcome of students' performance using the standard
      setting method with the equivalent outcome they would have obtained using the
      absolute grading method. It involved the comparison of fail, pass, honors and
      distinction grades in Digestive System, Endocrine System, Cardiovascular System
      and Health and the Environment courses in the MBBS Stage I examination. The
      performance in Cardiovascular System was significantly better with the standard
      setting method (chi2 = 27.53; p < 0.01), median score in the honors range
      compared with the absolute grading method where the median score was in the pass
      range. On the other hand, the performance in Endocrine System was significantly
      better using the absolute grading method (chi2 = 27.30; p < 0.01), with median
      score in the honors range compared with the standard setting method where the
      median score was in the pass range. There was no difference in the performance in
      Digestive System (chi2 = 7.45; p = 0.06), median score in the pass range and
      Health and the Environment (chi2 = 6.34; p = 0.09), median score in the honors
      range; between the standard setting and absolute grading methods (Wilcoxon's
      signed rank). The overall pass, honors, distinction and failure rates were also
      identical in both methods (Mann Whitney U test). This suggests that overall the
      outcome of the students' performance in the standard setting method compared with
      the absolute grading method were not significantly different. 

PMID- 26196576
TI  - Erythrocyte Osmotic Fragility and Excitability Score in Rabbit fed Hibiscus
      Sabdariffa in Graded Level.
AB  - This study was conducted for 10 weeks with the aim of investigating the
      erythrocyte membrane integrity as measured by erythrocyte osmotic fragility and
      excitability scores of rabbits fed graded level of Hibiscus sabdariffa calyx
      (HSC). Twenty weaners' rabbit of both sexes were used for the study and were
      placed on four experimental diets which contain the following percentages of HSC
      0 %, 25 %, 50 %, 75 %, as feed additive and were added at 0 g, 62.5 g, 125 g,
      187.5 g designated as T1, T2, T3 and T4 experimental diets. Excitability scores
      were measured weekly as described by Voisnet et al. (1997). At the end of the
      experiment, the rabbits were slaughtered by severing the jugular vein. A Blood
      sample (2 ml) was collected from each rabbit into sampled bottles, containing the
      Na EDTA as anticoagulant for hematological analysis. Packed cell volume (PCV)
      Haemoglobin concentration (Hb), Total red blood cell (RBC) count, Total leukocyte
      count as well as differential leukocyte was determined using standard method. The
      percentage haemolysis recorded at 0.3 % to 0.8 % was significantly (P < 0.05)
      higher in rabbits in T1 compared to the remaining 3 diets. The result of
      excitability score shows that rabbit on diet 1 and 2 had a lower value which was
      significantly (P < 0.05) lower than rabbits on diets 3 and 4 with a value of 65.5
      +/- 5.0 and 70.00 +/- 5.50 % respectively. In conclusion this study demonstrated
      for the first time that chronic administration of HSC improves haematological
      parameters, brain mood and function as well as maintaining erythrocyte membrane
      integrity.

PMID- 26196575
TI  - Effect of Chronic Administration of Methanol Extract of Moringa Oleifera on Some
      Biochemical Indices in Female Wistar Rats.
AB  - The study was conducted to investigate safety associated with prolonged
      consumption of Moringa oleifera leaves as beverage. Fourteen rats were used in
      this study. They were divided into 2 groups each containing 7 rats. Rats in group
      I received 2ml/kg of corn oil (standard vehicle drug). Animals in groups II were
      administered with 400mg/kg body of methanolic extract of Moringa oleifera (MEMO)
      for five weeks respectively. Serum collected was analyzed for alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin,
      globulin, blood urea nitrogen (BUN) and creatinine. There was significant
      (P<0.05) decrease in serum total protein, albumin, globulin and AST activity. The
      activity of ALT decreased but not significant. Similarly, 400mg/kg body of MEMO
      led to significant (P<0.05) decrease in serum BUN and creatinine. All
      experimental animals that received 400mg/kb of MEMO had significant (P<0.05)
      decrease in body weight from week to week 4 of the experiment. Taken together,
      400mg/kg body of MEMO seemed to be toxic to the liver with apparently no toxicity
      in the kidney. Hence, prolonged exposure is not advisable as such could portend
      danger to the liver. 

PMID- 26196577
TI  - Estimation of Plasma Arginine Vasopressin Concentration Using Thirst Perception
      and Plasma Osmolality Values.
AB  - In human, thirst and antidiuretic hormone (ADH) are controlled by similar
      sensitive osmoregulatory mechanisms such that above a certain osmotic threshold
      (280-288 mOsm/kg H20) there is a linear relationship between the increase in
      plasma osmolality and increase in ADH and thirst. The purpose of this study was
      to estimate plasma arginine vasopressin (PAVP) using thirst perception (TP) and
      plasma osmolality (POSM) values before and at 60 minutes in control or euhydrate
      (group A, 0.0 ml/kg body weight of distilled water), hydrated (group B, 7.1 ml/kg
      body weight of distilled water) and dehydrated (group C, 0.0 ml/kg body weight of
      distilled water) subjects. A total of twenty five (25) subjects between the ages
      of 18 and 30 years were used for the study. Calculated POSM and TP values were
      used to estimate the PAVP concentration. Data were presented as Mean +/- SEM.
      Analyses of results were done using ANOVA and Student t-test. The estimated
      values of PAVP using TP and POSM respectively at baseline levels were similar in
      euhydrate (2.22+2.00 vs 2.40+2.10 pg/ml), hydrate (2.22+1.34 vs 2.40+1.72 pg/ml)
      and in dehydrate (7.05+1.70 vs 6.92+1.94 pg/ml). Sixty minutes later, the values
      remained similar in euhydrate (3.29+2.40 vs 4.16+2.10 pg/ml), hydrate (1.92+1.60
      vs 1.79+1.25 pg/ml) and in dehydrate (8.40+1.40 vs 9.20+1.50 pg/ml). The results
      show that there was a positive relationship between PAVP calculated from TP and
      POSM values. We therefore concluded that plasma arginine vasopressin
      concentration may be estimated using thirst perception and/or plasma osmolality
      values. Estimation of PAVP using plasma osmolar changes affected by glucose and
      urea may be inappropriate.

PMID- 26196578
TI  - Lactational Vitamin E Protects Against the Histotoxic Effects of Systemically
      Administered Vanadium in Neonatal Rats.
AB  - The work investigated the protective role of lactational vitamin E administration
      on vanadium-induced histotoxicity. Three groups of Wistar rats, with each group
      comprising of two dams and their pups, were used in this study. Group I pups were
      administered intraperitoneal injection of sterile water at volumes corresponding
      to the dose rate of the vanadium (sodium metavanadate) treated group from
      postnatal day (PND) 1-14 while those in Group II were administered
      intraperitoneal injection of 3mg/kg vanadium from PND 1-14. Group III pups were
      administered intraperitoneal injection of 3mg/kg vanadium while the dam received
      oral vitamin E (500 mg) concurrently every 72 hours. The results showed that
      group II pups exhibited histopathological changes which included seminiferous
      tubule disruption of the testes characterised by vacuolar degeneration and
      coagulative necrosis of spermatogonia and Sertoli cells with reduction in
      mitosis, and areas of interstitial thickening with fibroblast proliferation. In
      addition, the lungs showed disruption of the bronchiolar wall and denudation of
      the bronchiolar respiratory epithelium while the liver showed hydropic
      degeneration and coagulative necrosis of the centrilobular hepatocytes. These
      histotoxic changes were ameliorated in the vanadium + vitamin E group. We
      conclude that lactational vitamin E protects against the histotoxic effects of
      vanadium and could be a consideration for supplementation in the occupationally
      and environmentally exposed neonates. However, caution should be taken in vitamin
      E supplementation because there is still equivocal evidence surrounding its
      benefits as a supplement at the moment.

PMID- 26196579
TI  - The Aqueous Calyx Extract of Hibiscus sabdariffa Lowers Blood Pressure and Heart
      Rate via Sympathetic Nervous System Dependent Mechanisms.
AB  - The antihypertensive effect of Hibiscus sabdariffa (HS) has been validated in
      animals and man. This study tested the hypothesis that its hypotensive effect may
      be sympathetically mediated. The cold pressor test (CPT) and handgrip exercise
      (HGE) were performed in 20 healthy subjects before and after the oral
      administration of 15mg/Kg HS. The blood pressure (BP) and heart rate (HR)
      responses were measured digitally. Mean arterial pressure (MAP; taken as
      representative BP) was calculated. Results are expressed as mean +/-SEM. P<0.05
      was considered significant. CPT without HS resulted in a significant rise in MAP
      and HR (111.1+/-2.1mmHg and 100.8+/-2.0/min) from the basal values (97.9+/
      1.9mmHg and 87.8+/-2.1/min; P<0.0001 respectively). In the presence of HS, CPT
      induced changes (DeltaMAP=10.1+/-1.7mmHg; DeltaHR= 8.4+/-1.0/min) were
      significantly reduced compared to its absence (DeltaMAP= 13.2+/-1.2mmHg; DeltaHR=
      13.8+/-1.6/min; P<0.0001 respectively). The HGE done without HS also resulted in
      an increase in MAP and HR (116.3+/-2.1mmHg and 78.4+/-1.2/min) from the basal
      values (94.8+/-1.6mmHg and 76.1+/-1.0/min; p<0.0001 respectively). In the
      presence of HS the HGE-induced changes (DeltaMAP= 11.5+/-1.0mmHg; DeltaHR= 3.3+/
      1.0/min) were significantly decreased compared to its absence (DeltaMAP=21.4+/
      1.2mmHg; DeltaHR= 12.8+/-2.0/min; P<0.0001 respectively). The CPT and HGE 
      induced increases in BP and HR suggest Sympathetic nervous system activation.
      These increases were significantly dampened by HS suggesting, indirectly, that
      its hypotensive effect may be due to an attenuation of the discharge of the
      sympathetic nervous system. 

PMID- 26196580
TI  - Effect of Mobile Phone Radiofrequency Electromagnetic Fields on.
AB  - Since cell phones emit radiofrequency electromagnetic fields (EMFs), this study
      tested the hypothesis that cell phones placed near the heart may interfere with
      the electrical rhythm of the heart or affect the blood pressure. Following
      informed consent, eighteen randomly selected apparently healthy male volunteers
      aged 21.44 +/- 0.53 years had their blood pressure, pulse rates and ECG measured
      before and after acute exposure to a cell phone. The ECG parameters obtained
      were: heart rate (HR), QRS complex duration (QRS), PR interval (PR) and Corrected
      QT interval (QTc). Results are presented as mean +/- SEM. Statistical analyses
      were done using two-tailed paired t test for blood pressure and pulse rate data
      and one way ANOVA with a post hoc Tukey test for the ECG data. P<0.05 was
      considered statistically significant. The blood pressure and pulse rates before
      and after exposure to the cell phone showed no significant difference. The ECG
      parameters (HR: beats/min, QRS:ms, PR:ms and QTc respectively) did not differ
      before (66.33 +/- 2.50, 91.78 +/- 1.36, 151.67 +/- 5.39 and 395.44 +/- 4.96),
      during (66.33 +/- 2.40, 91.11 +/- 1.61, 153.67 +/- 5.06 and 394.33 +/- 4.05) and
      after calls (67.22 +/- 2.77, 91.11 +/- 1.67, 157.44 +/- 4.46 and 396.56 +/- 4.93)
      compared to baseline (67.17 +/- 2.19, 94.33 +/- 1.57, 150.56 +/- 4.93 and 399.56
      +/- 3.88). These results suggest that acute exposure to EMFs from cell phones
      placed near the heart may not interfere with the electrical activity of the heart
      or blood pressure in healthy individuals. 

PMID- 26196581
TI  - The Effect of Intranasal Desmopressin Spray on Basal and Total Tear Secretions in
      Healthy Subjects.
AB  - Many hormones have been implicated in dry eye syndrome. This study was carried
      out to investigate the effects of antidiuretic hormone (ADH) on tear secretion.
      Fifty (50) healthy male and female volunteers between the ages of 21 and 70 years
      were studied. They were given exogenous ADH in the form of intranasal
      desmopressin spray (DDAVP). Total and basal tear secretions were assessed using
      the Schirmer strip at baseline and at 30 minutes intervals for a period of 180
      minutes after the nasal administration of 10 MUg desmopressin spray into each
      nostril. Blood samples were taken before and 60 minutes after desmopressin
      administration for the determination of plasma osmolality and plasma ADH
      concentrations. Results showed a significant reduction (p<0.001) in the means of
      total and basal tear secretions from baselines of 20.04 +/- 1.19 and 14.64 +/-
      1.00 mm/5 mins to 12.80 +/- 0.75 and 9.68 +/- 0.72 mm/5 mins peak reductions
      respectively. The peak reduction was observed at 90 minutes assessment time after
      desmopressin administration. The difference in mean total tear secretions between
      males and females were statistically significant (p < 0.05). The difference in
      mean plasma osmolality before and 60 minutes after desmopressin administration
      was not statistically significant. However, there was a significant increase
      (p<0.05) in mean ADH concentration after DDAVP administration. It is concluded
      from this study that exogenous ADH reduces tear secretion in man with associated
      increase in ADH concentration but no change in plasma osmolality.

PMID- 26196582
TI  - Antioxidant Effects of Methanol Extract of Allium cepa linn on Cyanide-induced
      Renal Toxicity in Male Wistar Rats.
AB  - The protective effects of onion was assessed in the Kidney of rats following sub
      acute exposure to cyanide. These effects were compared to those of sodium
      thiosulphate (Na2S2O3), a classical antidote of cyanide toxicity. The rats were
      divided into 6 groups of 6 animals each. Group 1 was administered distilled
      water, Group 2,3,4, 5, and 6 were administered 600 mg onion/kg bwt/day, 7 mg
      KCN/kg bwt/day, 300 mg onion/kg bwt/day+ 7 mg KCN/kg bwt/day, 600 mg onion/kg
      bwt/day+ 7mgKCN/kg bwt/day, 600mg Na2S2O3/kg bwt/day+ 7mgKCN/kg bwt/day
      respectively for 2 weeks. Group 3, 4 and 5 were pre-administered with 300mg
      onion/kg bwt/day, 600mg onion/kg bwt/day and 600mg Na2S2O3 /kg bwt/day
      respectively for 2 weeks. Serum and urine creatinine and urea level were assessed
      as a measure of kidney function. Oxidative stress and antioxidant parameters were
      estimated in Kidney. Serum creatinine and urea levels were significantly higher
      in the cyanide treated rats compared with control. This was accompanied by
      significant reduction in the urine level of creatinine and urea. Co
      administration with onion extract and Na2S2O3 reverse the situation in both the
      serum and urine. The level of malondialdehyde (MDA) in rats treated with cyanide
      (3.846+/-0.20MUg/g) was significantly increased in the kidney relative to control
      (0.691+/-0.15MUg/g). This was accompanied with a decreased in antioxidant enzymes
      Superoxide Dismutase (SOD) (2.0+/-0.09U/mg), Catalase (CAT) (0.014+/
      0.001katf),Glutathione-S-Tranferase (GST) (0.015+/-0.009nMol/mg) and non
      enzymatic antioxidant Reduced Glutathione (GSH) (4.006+/-0.09MUg/ml) compared
      with control (4.8+/-0.13 U/mg, 0.047+/-0.001 katf, 0.022+/-0.0013 nMol/mg,
      6.802+/-0.2 MUg/ml respectively). Co-administration with onion extract and
      Na2S2O3 significantly increased these antioxidant enzymes and significantly
      decreased the concentration of malondialdehyde in the kidney. The results
      indicate that onion extract reduced lipid peroxidation in the kidney and
      increased antioxidant status of animals exposed to cyanide in a dose dependent
      manner.

PMID- 26196583
TI  - Some Aspects of the State-of-the-Arts in Biomedical Science Research: A
      Perspective for Organizational Change in African Academia.
AB  - In the biomedical sciences, there is need to generate solutions for Africa's
      health and economic problems through the impact of university research. To guide
      organizational transformation, the author here presents some aspects of the state
      of-the-arts of biomedical science research in advanced countries using a
      perspective derived from the FASEB journal publications. The author examines the
      thirty three peer reviewed scientific research articles in a centennial (April
      2012) issue of the FASEB Journal [Volume 26(4)] using the following parameters:
      number of authors contributing to the paper; number of academic departments
      contributing to the paper; number of academic institutions contributing to the
      paper; funding of the research reported in the article. The articles were written
      by 7.97+/-0.61 authors from 3.46+/-0.3 departments of 2.79+/-0.29 institutions.
      The contributors were classified into four categories: basic sciences, clinical
      sciences, institutions and centers, and programs and labs. Amongst the
      publications, 21.2% were single disciplinary. Two tier collaboration amongst any
      two of the four categories were observed in 16/33 (48.5%) of the articles. Three
      tier and four tier collaborations were observed amongst 7/33 (21.2%) and 3/33
      (9%) of the articles respectively. Therefore 26/33 (78.7%) of the articles were
      multidisciplinary. Collaborative efforts between basic science and clinical
      science departments were observed in 9/33 (27.3%) articles. Public funding
      through government agencies provided 85 out of a total of 143 (59.5%) grants. The
      collaborative and multidisciplinary nature and government support are
      characteristic of biomedical science in the US where research tends to result in
      solutions to problems and economic benefits. 

PMID- 26196585
TI  - Origin of life. Primordial genetics: Information transfer in a pre-RNA world
      based on self-replicating beta-sheet amyloid conformers.
AB  - The question of the origin of life on Earth can largely be reduced to the
      question of what was the first molecular replicator system that was able to
      replicate and evolve under the presumably very harsh conditions on the early
      Earth. It is unlikely that a functional RNA could have existed under such
      conditions and it is generally assumed that some other kind of information system
      preceded the RNA world. Here, I present an informational molecular system that is
      stable, self-replicative, environmentally responsive, and evolvable under
      conditions characterized by high temperatures, ultraviolet and cosmic radiation.
      This postulated pregenetic system is based on the amyloid fold, a functionally
      unique polypeptide fold characterized by a cross beta-sheet structure in which
      the beta strands are arranged perpendicular to the fiber axis. Beside an
      extraordinary structural robustness, the amyloid fold possesses a unique ability
      to transmit information by a three-dimensional templating mechanism. In
      amyloidogenesis short peptide monomers are added one by one to the growing end of
      the fiber. From the same monomeric subunits several structural variants of
      amyloid may be formed. Then, in a self-replicative mode, a specific amyloid
      conformer can act as a template and confer its spatially encoded information to
      daughter molecular entities in a repetitive way. In this process, the specific
      conformational information, the spatially changed organization, is transmitted;
      the coding element is the steric zipper structure, and recognition occurs by
      amino acid side chain complementarity. The amyloid information system fulfills
      several basic requirements of a primordial evolvable replicator system: (i) it is
      stable under the presumed primitive Earth conditions, (ii) the monomeric building
      blocks of the informational polymer can be formed from available prebiotic
      compounds, (iii) the system is self-assembling and self-replicative and (iv) it
      is adaptive to changes in the environment and evolvable. 

PMID- 26196586
TI  - Protocol for the Hall Technique study: A trial to measure clinical effectiveness
      and cost-effectiveness of stainless steel crowns for dental caries restoration in
      primary molars in young children.
AB  - BACKGROUND: The Hall Technique (HT) is a carious primary molar treatment that
      does not require local analgesia, carious tissue removal or tooth preparation.
      The carious lesions in carefully selected teeth are sealed with a stainless steel
      crown (preformed metal crown). The study aims are to determine the clinical
      effectiveness, acceptability and cost-effectiveness of the HT for management of
      carious lesions in young dental patients. METHODS/DESIGN: Children, aged 3
      7years, with a primary molar tooth with a carious lesion extending no further
      than the middle third of dentine, with no signs or symptoms of pulp inflammation
      or infection, and attending one of three community agencies are recruited. Target
      sample size is 220. A control tooth with an intra-coronal restoration is sourced
      from the same mouth. The primary outcome is the period of time free from further
      treatment. The assessments are scheduled at 6, 12 and 24months. In addition to
      the clinical assessment, acceptability of the HT will be assessed via
      questionnaires among patients and their primary carers at baseline, 6, 12 and
      24months. Cost-outcome description and cost-effectiveness analysis from
      healthcare provider and societal perspective will be conducted. DISCUSSION: The
      clinical effectiveness, acceptability and cost-effectiveness of the HT in the
      community dental setting will be evaluated. The results of this study will
      determine the implementation of HT in the management of dental caries in young
      children.

PMID- 26196587
TI  - Rickettsia felis Infection among Humans, Bangladesh, 2012-2013.

PMID- 26196588
TI  - The Contributions of Thrombophilic Mutations to Genetic Susceptibility to Deep
      Venous Thrombosis in Iraqi Patients.
AB  - BACKGROUND AND AIMS: There is a paucity of data on the contribution of various
      thrombophilic mutations to the development of venous thrombosis in Iraqi
      patients. Therefore we designed a study to assess the frequencies of known
      thrombophilic mutations in this population. METHODS: 100 consecutive Iraqi
      patients with color Doppler confirmed deep venous thrombosis of the lower
      extremities and 100 age- and sex-matched healthy controls were enrolled in the
      study. Their DNAs were tested by multiplex polymerase chain reaction (PCR)
      followed by reverse hybridization for factor V Leiden (FVL), the prothrombin (PT)
      G20210A SNP, and the MTHFR C677T SNP. The factor V A4070G mutation was assessed
      by restriction fragment length polymorphism-PCR. RESULTS: The prevalence of FVL
      was 13% in patients versus 2% in controls (odd ratios [OR] 7.3; p=0.007).
      Patients with recurrent thrombosis also had a significantly higher frequency of
      Factor V Leiden (OR 8.4, p=0.0007). The prothrombin G20210A, SNP, the factor V
      A4070G SNP, and the MTHFR 677 TT genotypes were present among patients at 5%, 9%,
      and 11%, respectively, and among controls at 2%, 6%, and 6%; none of these single
      mutation prevalence differences were significant. Interestingly, however, when
      these polymorphisms were studied in aggregate we found that 24% of patients had
      two or more thrombophilic alleles, compared to only 8% of the controls (OR 3.6;
      p=0.002). This subgroup included significantly more patients with proximal
      (p=0.007) and recurrent thrombosis (p=0.012), as well as younger patients (<=40
      years) (p=0.026). CONCLUSION: Two or more thrombophilic alleles, as well as FVL
      on its own, were both significantly associated with an increased risk of venous
      thrombosis and recurrence in Iraqi patients. Single thrombophilic mutations on
      their own were not associated with an increased risk.

PMID- 26196589
TI  - Elevated Plasma Soluble CD14 Levels Correlate with the Monocyte Response Status
      During Hantaan Virus Infection in Humans.
AB  - Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal
      syndrome (HFRS) in humans. CD14, a pattern recognition receptor recognizing
      lipopolysaccharide, is highly expressed on monocytes and can be shed as soluble
      CD14 (sCD14) upon monocyte activation. To understand the role of sCD14 in HFRS,
      the sCD14 plasma concentrations from 45 HFRS patients were quantified, and the
      relationships between the plasma sCD14 level and the monocyte response status and
      clinical parameters were analyzed. The plasma sCD14 levels were significantly
      higher in the HFRS patients and they correlated with monocyte expansion and
      activation, which were characterized by increased blood monocyte counts, the
      proportion of CD14(++)CD16(+) intermediate monocytes, as well as elevated plasma
      tumor necrosis factor-alpha (TNF-alpha) and soluble CD163 (sCD163) levels.
      Additionally, the high plasma sCD14 levels positively correlated with white blood
      cell counts and blood urea nitrogen levels and negatively correlated with
      platelet counts in the HFRS patients. Taken together, our data indicate that
      elevated plasma sCD14 levels are associated with the monocyte response status
      during HTNV infection in humans. 

PMID- 26196590
TI  - Characterization of SLC22A18 as a tumor suppressor and novel biomarker in
      colorectal cancer.
AB  - SLC22A18, solute carrier family 22, member 18, has been proposed to function as a
      tumor suppressor based on its chromosomal location at 11p15.5, mutations and
      aberrant splicing in several types of cancer and down-regulation in glioblastoma.
      In this study, we sought to demonstrate the significance of SLC22A18 as a tumor
      suppressor in colorectal cancer (CRC) and provide mechanistic bases for its
      function. We first showed that the expression of SLC22A18 is significantly down
      regulated in tumor tissues using matched normal-tumor samples from CRC patients.
      This finding was also supported by publically accessible data from The Cancer
      Genome Atlas (TCGA). Functionally, SLC22A18 inhibits colony formation and induces
      of G2/M arrest consistent with being a tumor suppressor. Interestingly,
      suppression of KRAS by RNA interference promotes SLC22A18 expression, and
      expression of SLC22A18 in turn inhibits KRAS(G12D)-mediated anchorage independent
      growth of NIH3T3 cells indicating a mutual negative interaction. Finally, we
      evaluated diagnostic and prognostic values of SLC22A18 using clinical and gene
      expression data from TCGA which revealed a significantly worse long-term
      prognosis for patients with low level SLC22A18 expression. In sum, we established
      SLC22A18 as a tumor suppressor in colon epithelial cells and propose that
      SLC22A18 is potentially a marker of diagnostic and prognostic values.

PMID- 26196591
TI  - Raising Darwin's consciousness : Female sexuality and the prehominid origins of
      patriarchy.
AB  - Sociobiologists and feminists agree that men in patriarchal social systems seek
      to control females, but sociobiologists go further, using Darwin's theory of
      sexual selection and Trivers's ideas on parental investment to explain why males
      should attempt to control female sexuality. From this perspective, the stage for
      the development under some conditions of patriarchal social systems was set over
      the course of primate evolution.Sexual selection encompasses both competition
      between males and female choice. But in applying this theory to our "lower
      origins" (prehominid ancestors), Darwin assumed that choices were made by
      essentially "coy" females. I argue here that female solicitation of multiple
      males (either simultaneously or sequentially, depending on the breeding system)
      characterized prehominid females; this prehominid legacy of cyclical sexual
      assertiveness, itself possibly a female counter-strategy to male efforts to
      control the timing of female reproduction, generated further male counter
      strategies. This dialectic had important implications for emerging hominid mating
      systems, human evolution, and the development of patriarchal arrangements in some
      human societies. For hominid males who will invest in offspring, there would be
      powerful selection for emotions, behaviors, and customs that ensure them
      certainty of paternity. The sexual modesty that so struck Darwin can be explained
      as a recent evolved or learned (perhaps both) adaptation in women to avoid
      penalties imposed by patrilines on daughters and mates who failed to conform to
      the patriline's prevailing norms for their sex. Other supposedly innate
      universals, such as female preferences for wealthy husbands, are also likely to
      be facultative accommodations by women to constraints set up when patrilines
      monopolized resources needed by females to survive and reproduce, and passed on
      intergenerational control of these resources preferentially to sons. 

PMID- 26196592
TI  - The evolutionary context of chronic allergic conditions : The Hiwi of Venezuela.
AB  - The question of why populations with ecologies that resemble our evolutionary
      past rarely experience allergic conditions such as asthma has intrigued many
      biomedical scientists. Here we present descriptive data on the ecological context
      of allergic sensitization among the Hiwi of southwestern Venezuela and suggest
      reasons for why this and other lowland South American Indian groups do not
      express the allergic response at levels seen in industrialized contexts. Allergic
      sensitization among the Hiwi appears to be negligible. This absence occurs in the
      context of high exposure to macroparasites (mainly hookworm), nutritional stress,
      frequent and prolonged breastfeeding, low indoor allergen deposition, and few
      hours spent per day indoors. We conclude that seeking unidimensional answers to
      the question of why isolated human groups generally experience few allergic
      conditions is potentially flawed because allergies are produced by a multifaceted
      immunoglobulin E (IgE) system that responds in complex ways to the environmental
      and behavioral exposures we examined. Instead, we propose a general model of
      physiological trade-offs in energy allocation between production of IgE of
      undefined specificity and production of allergen-specific IgE. In addition, we
      consider the simultaneous effects that exposures such as nutritional stress,
      allergen exposure, and breastfeeding may have on these trade-offs. 

PMID- 26196593
TI  - Segmentation in behavior and what it can tell us about brain function.
AB  - Natural human behavior is segmented into action units, functionally related
      groups of movements with durations of a few seconds. This phenomenon can also be
      found in nonhuman primates and other mammals. In humans, a similar segmentation
      can be found in planning, preparatory behavior, perception, and speech.Temporal
      segmentation may be related to the functioning of short-term memory. Segmentation
      may thus be a central feature of neuronal integration. Segment length was
      hitherto thought to be determined by either capacity constraints or temporal
      factors. Instead we show that segment length depends on the interplay between
      capacity and temporal factors. 

PMID- 26196595
TI  - Cholesterol increases the open probability of cardiac KACh currents.
AB  - Cholesterol is one of the major lipid components of membranes in mammalian cells.
      In recent years, cholesterol has emerged as a major regulator of ion channel
      function. The most common effect of cholesterol on ion channels in general and on
      inwardly rectifying potassium (Kir) channels in particular is a decrease in
      activity. In contrast, we have recently shown that native G-protein gated Kir
      (GIRK or Kir3) channels that underlie atrial KACh currents are up-regulated by
      cholesterol. Here we unveil the biophysical basis of cholesterol-induced increase
      in KACh activity. Using planar lipid bilayers we show that cholesterol
      significantly enhances the channel open frequency of the Kir3.1/Kir3.4 channels,
      which underlie KACh currents. In contrast, our data indicate that cholesterol
      does not affect their unitary conductance. Furthermore, using fluorescent and
      TIRF microscopy as well as surface protein biotinylation, we also show that
      cholesterol enrichment in vitro has no effect on surface expression of GFP-tagged
      channels expressed in Xenopus oocytes or transfected into HEK293 cells. Together,
      these data demonstrate for the first time that cholesterol enhances Kir3-mediated
      current by increasing the channel open probability. 

PMID- 26196596
TI  - Genotype-guided dose adjustment for the use of efavirenz in HIV treatment.

PMID- 26196597
TI  - Crimean-Congo haemorrhagic fever and secondary bacteraemia in Turkey.

PMID- 26196598
TI  - Host-Guest Carbon Dots for Enhanced Optical Properties and Beyond.
AB  - Carbon dots, generally small carbon nanoparticles with various forms of surface
      passivation, have achieved the performance level of semiconductor quantum dots in
      the green spectral region, but their absorption and fluorescence in red/near-IR
      are relatively weaker. Conceptually similar to endofullerenes, host-guest carbon
      dots were designed and prepared with red/near-IR dyes encapsulated as guest in
      the carbon nanoparticle core. Beyond the desired enhancement in optical
      properties, the host-guest configuration may significantly broaden the field of
      carbon dots. 

PMID- 26196599
TI  - Phylogeography of Influenza A(H3N2) Virus in Peru, 2010-2012.
AB  - It remains unclear whether lineages of influenza A(H3N2) virus can persist in the
      tropics and seed temperate areas. We used viral gene sequence data sampled from
      Peru to test this source-sink model for a Latin American country. Viruses were
      obtained during 2010-2012 from influenza surveillance cohorts in Cusco, Tumbes,
      Puerto Maldonado, and Lima. Specimens positive for influenza A(H3N2) virus were
      randomly selected and underwent hemagglutinin sequencing and phylogeographic
      analyses. Analysis of 389 hemagglutinin sequences from Peru and 2,192 global
      sequences demonstrated interseasonal extinction of Peruvian lineages. Extensive
      mixing occurred with global clades, but some spatial structure was observed at
      all sites; this structure was weakest in Lima and Puerto Maldonado, indicating
      that these locations may experience greater viral traffic. The broad diversity
      and co-circulation of many simultaneous lineages of H3N2 virus in Peru suggests
      that this country should not be overlooked as a potential source for novel
      pandemic strains. 

PMID- 26196600
TI  - In Situ Synthesis of Magnetic Field-Responsive Hemicellulose Hydrogels for Drug
      Delivery.
AB  - A one-pot synthetic methodology for fabricating stimuli-responsive hemicellulose
      based hydrogels was developed that consists of the in situ formation of magnetic
      iron oxide (Fe3O4) nanoparticles during the covalent cross-linking of O-acetyl
      galactoglucomannan (AcGGM). The Fe3O4 nanoparticle content controlled the thermal
      stability, macrostructure, swelling behavior, and magnetization of the hybrid
      hydrogels. In addition, the magnetic field-responsive hemicellulose hydrogels
      (MFRHHs) exhibited excellent adsorption and controlled release profiles with
      bovine serum albumin (BSA) as the model drug. Therefore, the MFRHHs have great
      potential to be utilized in the biomedical field for tissue engineering
      applications, controlled drug delivery, and magnetically assisted bioseparation.
      Magnetic field-responsive hemicellulose hydrogels, prepared using a
      straightforward one-step process, expand the applications of biomass-derived
      polysaccharides by combining the renewability of hemicellulose and the magnetism
      of Fe3O4 nanoparticles. 

PMID- 26196602
TI  - Editorial: Can There Be a Physics of the Brain?

PMID- 26196603
TI  - Quantum Bounds on Heat Transport Through Nanojunctions.
AB  - We derive rigorous quantum mechanical bounds for the heat current through a
      nanojunction connecting two thermal baths at different temperatures. Based on
      exact sum rules, these bounds compliment the well-known quantum of thermal
      conductance kappa_{Q}=pik_{B}^{2}T/6h, which provides a bound for low-temperature
      heat transport in all systems, but is saturated only for noninteracting
      transport. In contrast, our bounds are saturated at high temperatures-but still
      in the quantum regime-even when interactions are very strong. We evaluate these
      bounds for harmonic and strongly anharmonic junction models and compare with
      numerical approaches. 

PMID- 26196604
TI  - Simple Explanation of the Quantum Limits of Genuine n-Body Nonlocality.
AB  - Quantum n-body correlations cannot be explained with (n-1)-body nonlocality.
      However, this genuine n-body nonlocality cannot surpass certain bounds. Here we
      address the problem of identifying the principles responsible for these bounds.
      We show that, for any n>=2, the exclusivity principle, as derived from axioms
      about sharp measurements, and a technical assumption give the exact bounds
      predicted by quantum theory. This provides a unified explanation of the bounds of
      single-body contextuality and n-body nonlocality, and connects two programs
      towards understanding quantum theory. 

PMID- 26196605
TI  - Bounding Quantum Contextuality with Lack of Third-Order Interference.
AB  - Recently, many simple principles have been proposed that can explain quantum
      limitations on possible sets of experimental probabilities in nonlocality and
      contextuality experiments. However, few implications between these principles are
      known. Here it is shown that the lack of irreducible third-order interference (a
      generalization of the idea that no probabilistic interference remains unaccounted
      for once we have taken into account interference between pairs of slits in a n
      sit experiment) implies the principle known as the E principle or consistent
      exclusivity (that, if each pair of a set of experimental outcomes are exclusive
      alternatives in some measurement, then their probabilities are consistent with
      the existence of a further measurement in which they are all exclusive). This is
      a step towards a more unified understanding of quantum nonlocality and
      contextuality, which promises to allow derivations of important results from
      minimal, easily grasped assumptions. As one example, this result implies that
      lack of third-order interference bounds violation of the Clauser-Horne-Shimony
      Holt-Bell inequality to 2.883. 

PMID- 26196601
TI  - Genetic evidence for two founding populations of the Americas.
AB  - Genetic studies have consistently indicated a single common origin of Native
      American groups from Central and South America. However, some morphological
      studies have suggested a more complex picture, whereby the northeast Asian
      affinities of present-day Native Americans contrast with a distinctive morphology
      seen in some of the earliest American skeletons, which share traits with present
      day Australasians (indigenous groups in Australia, Melanesia, and island
      Southeast Asia). Here we analyse genome-wide data to show that some Amazonian
      Native Americans descend partly from a Native American founding population that
      carried ancestry more closely related to indigenous Australians, New Guineans and
      Andaman Islanders than to any present-day Eurasians or Native Americans. This
      signature is not present to the same extent, or at all, in present-day Northern
      and Central Americans or in a ~12,600-year-old Clovis-associated genome,
      suggesting a more diverse set of founding populations of the Americas than
      previously accepted. 

PMID- 26196606
TI  - Demonstration of Quantum Nonlocality in the Presence of Measurement Dependence.
AB  - Quantum nonlocality stands as a resource for device independent quantum
      information processing (DIQIP), such as, for instance, device independent quantum
      key distribution. We investigate, experimentally, the assumption of limited
      measurement dependence, i.e., that the measurement settings used in Bell
      inequality tests or DIQIP are partially influenced by the source of entangled
      particle and/or by an adversary. Using a recently derived Bell-like inequality
      [G. Putz, Phys. Rev. Lett. 113, 190402 (2014)] and a 99% fidelity source of
      partially entangled polarization photonic qubits, we obtain a clear violation of
      the inequality, excluding a much larger range of measurement dependent local
      models than would be possible with an adapted Clauser-Horne-Shimony-Holt (CHSH)
      inequality. It is therefore shown that the measurement independence assumption
      can be widely relaxed while still demonstrating quantum nonlocality. 

PMID- 26196607
TI  - Individual Quantum Probes for Optimal Thermometry.
AB  - The unknown temperature of a sample can be estimated with minimal disturbance by
      putting it in thermal contact with an individual quantum probe. If the
      interaction time is sufficiently long so that the probe thermalizes, the
      temperature can be read-out directly from its steady state. Here we prove that
      the optimal quantum probe, acting as a thermometer with maximal thermal
      sensitivity, is an effective two-level atom with a maximally degenerate excited
      state. When the total interaction time is insufficient to produce full
      thermalization, we optimize the estimation protocol by breaking it down into
      sequential stages of probe preparation, thermal contact, and measurement. We
      observe that frequently interrogated probes initialized in the ground state
      achieve the best performance. For both fully and partly thermalized thermometers,
      the sensitivity grows significantly with the number of levels, though
      optimization over their energy spectrum remains always crucial. 

PMID- 26196608
TI  - Heralded Storage of a Photonic Quantum Bit in a Single Atom.
AB  - Combining techniques of cavity quantum electrodynamics, quantum measurement, and
      quantum feedback, we have realized the heralded transfer of a polarization qubit
      from a photon onto a single atom with 39% efficiency and 86% fidelity. The
      reverse process, namely, qubit transfer from the atom onto a given photon, is
      demonstrated with 88% fidelity and an estimated efficiency of up to 69%. In
      contrast to previous work based on two-photon interference, our scheme is robust
      against photon arrival-time jitter and achieves much higher efficiencies. Thus,
      it constitutes a key step toward the implementation of a long-distance quantum
      network. 

PMID- 26196609
TI  - Iterated Gate Teleportation and Blind Quantum Computation.
AB  - Blind quantum computation allows a user to delegate a computation to an untrusted
      server while keeping the computation hidden. A number of recent works have sought
      to establish bounds on the communication requirements necessary to implement
      blind computation, and a bound based on the no-programming theorem of Nielsen and
      Chuang has emerged as a natural limiting factor. Here we show that this
      constraint only holds in limited scenarios, and show how to overcome it using a
      novel method of iterated gate teleportations. This technique enables drastic
      reductions in the communication required for distributed quantum protocols,
      extending beyond the blind computation setting. Applied to blind quantum
      computation, this technique offers significant efficiency improvements, and in
      some scenarios offers an exponential reduction in communication requirements. 

PMID- 26196610
TI  - Variational Matrix Product Operators for the Steady State of Dissipative Quantum
      Systems.
AB  - We present a new variational method based on the matrix product operator (MPO)
      ansatz, for finding the steady state of dissipative quantum chains governed by
      master equations of the Lindblad form. Instead of requiring an accurate
      representation of the system evolution until the stationary state is attained,
      the algorithm directly targets the final state, thus, allowing for a faster
      convergence when the steady state is a MPO with small bond dimension. Our
      numerical simulations for several dissipative spin models over a wide range of
      parameters illustrate the performance of the method and show that, indeed, the
      stationary state is often well described by a MPO of very moderate dimensions. 

PMID- 26196611
TI  - Neutral Black Rings in Five Dimensions are Unstable.
AB  - We study nonaxisymmetric linearized gravitational perturbations of the Emparan
      Reall black ring using numerical methods. We find an unstable mode whose onset
      lies within the "fat" branch of the black ring and continues into the "thin"
      branch. Together with previous results using Penrose inequalities that fat black
      rings are unstable, this provides numerical evidence that the entire black ring
      family is unstable. 

PMID- 26196612
TI  - Locality of Gravitational Systems from Entanglement of Conformal Field Theories.
AB  - The Ryu-Takayanagi formula relates the entanglement entropy in a conformal field
      theory to the area of a minimal surface in its holographic dual. We show that
      this relation can be inverted for any state in the conformal field theory to
      compute the bulk stress-energy tensor near the boundary of the bulk spacetime,
      reconstructing the local data in the bulk from the entanglement on the boundary.
      We also show that positivity, monotonicity, and convexity of the relative entropy
      for small spherical domains between the reduced density matrices of any state and
      of the ground state of the conformal field theory are guaranteed by positivity
      conditions on the bulk matter energy density. As positivity and monotonicity of
      the relative entropy are general properties of quantum systems, this can be
      interpreted as a derivation of bulk energy conditions in any holographic system
      for which the Ryu-Takayanagi prescription applies. We discuss an information
      theoretical interpretation of the convexity in terms of the Fisher metric. 

PMID- 26196613
TI  - Effective Field Theories from Soft Limits of Scattering Amplitudes.
AB  - We derive scalar effective field theories-Lagrangians, symmetries, and all-from
      on-shell scattering amplitudes constructed purely from Lorentz invariance,
      factorization, a fixed power counting order in derivatives, and a fixed order at
      which amplitudes vanish in the soft limit. These constraints leave free
      parameters in the amplitude which are the coupling constants of well-known
      theories: Nambu-Goldstone bosons, Dirac-Born-Infeld scalars, and Galilean
      internal shift symmetries. Moreover, soft limits imply conditions on the Noether
      current which can then be inverted to derive Lagrangians for each theory. We
      propose a natural classification of all scalar effective field theories according
      to two numbers which encode the derivative power counting and soft behavior of
      the corresponding amplitudes. In those cases where there is no consistent
      amplitude, the corresponding theory does not exist. 

PMID- 26196614
TI  - Updated Next-to-Next-to-Leading-Order QCD Predictions for the Weak Radiative B
      Meson Decays.
AB  - Weak radiative decays of the B mesons belong to the most important flavor
      changing processes that provide constraints on physics at the TeV scale. In the
      derivation of such constraints, accurate standard model predictions for the
      inclusive branching ratios play a crucial role. In the current Letter we present
      an update of these predictions, incorporating all our results for the
      O(alpha_{s}^{2}) and lower-order perturbative corrections that have been
      calculated after 2006. New estimates of nonperturbative effects are taken into
      account, too. For the CP- and isospin-averaged branching ratios, we find
      B_{sgamma}=(3.36+/-0.23)*10^{-4} and B_{dgamma}=(1.73_{-0.22}^{+0.12})*10^{-5},
      for E_{gamma}>1.6 GeV. Both results remain in agreement with the current
      experimental averages. Normalizing their sum to the inclusive semileptonic
      branching ratio, we obtain R_{gamma}=(B_{sgamma}+B_{dgamma})/B_{clnu}=(3.31+/
      0.22)*10^{-3}. A new bound from B_{sgamma} on the charged Higgs boson mass in the
      two-Higgs-doublet-model II reads M_{H^{+/-}}>480 GeV at 95% C.L.

PMID- 26196617
TI  - QCD inequalities for hadron interactions.
AB  - We derive generalizations of the Weingarten-Witten QCD mass inequalities for
      particular multihadron systems. For systems of any number of identical
      pseudoscalar mesons of maximal isospin, these inequalities prove that near
      threshold interactions between the constituent mesons must be repulsive and that
      no bound states can form in these channels. Similar constraints in less symmetric
      systems are also extracted. These results are compatible with experimental
      results (where known) and recent lattice QCD calculations, and also lead to a
      more stringent bound on the nucleon mass than previously derived,
      m_{N}>=3/2m_{pi}. 

PMID- 26196616
TI  - Possible New Resonance from W_{L}W_{L}-hh Interchannel Coupling.
AB  - We propose and theoretically study a possible new resonance caused by strong
      coupling between the Higgs-Higgs and the W_{L}W_{L} (Z_{L}Z_{L}) scattering
      channels, without regard to the intensity of the elastic interaction in either
      channel at low energy (that could be weak as in the standard model). We expose
      this channel-coupling resonance from unitarity and dispersion relations encoded
      in the inverse amplitude method, applied to the electroweak chiral Lagrangian
      with a scalar Higgs boson. 

PMID- 26196618
TI  - Angular Structure of the In-Medium QCD Cascade.
AB  - We study the angular broadening of a medium-induced QCD cascade. We derive the
      equation that governs the evolution of the average transverse momentum squared of
      the gluons in the cascade as a function of the medium length, and we solve this
      equation analytically. Two regimes are identified. For a medium of a not too
      large size, and for not too soft gluons, the transverse momentum grows with the
      size of the medium according to standard momentum broadening. The other regime,
      visible for a medium of a sufficiently large size and very soft gluons, is a
      regime dominated by multiple branchings: there, the average transverse momentum
      saturates to a value that is independent of the size of the medium. This
      structure of the in-medium QCD cascade is, at least qualitatively, compatible
      with the recent LHC data on dijet asymmetry. 

PMID- 26196620
TI  - Rotational State Microwave Mixing for Laser Cooling of Complex Diatomic
      Molecules.
AB  - We demonstrate the mixing of rotational states in the ground electronic state
      using microwave radiation to enhance optical cycling in the molecule yttrium (II)
      monoxide (YO). This mixing technique is used in conjunction with a frequency
      modulated and chirped continuous wave laser to slow longitudinally a cryogenic
      buffer-gas beam of YO. We generate a flux of YO below 10 m/s, directly loadable
      into a three-dimensional magneto-optical trap. This technique opens the door for
      laser cooling of diatomic molecules with more complex loss channels due to
      intermediate states.

PMID- 26196621
TI  - Optimal State Estimation for Cavity Optomechanical Systems.
AB  - We demonstrate optimal state estimation for a cavity optomechanical system
      through Kalman filtering. By taking into account nontrivial experimental noise
      sources, such as colored laser noise and spurious mechanical modes, we implement
      a realistic state-space model. This allows us to obtain the conditional system
      state, i.e., conditioned on previous measurements, with a minimal least-squares
      estimation error. We apply this method to estimate the mechanical state, as well
      as optomechanical correlations both in the weak and strong coupling regime. The
      application of the Kalman filter is an important next step for achieving real
      time optimal (classical and quantum) control of cavity optomechanical systems. 

PMID- 26196619
TI  - Measurement of Magic Wavelengths for the ^{40}Ca^{+} Clock Transition.
AB  - We demonstrate experimentally the existence of magic wavelengths and determine
      the ratio of oscillator strengths for a single trapped ion. For the first time,
      two magic wavelengths near 396 nm for the ^{40}Ca^{+} clock transition are
      measured simultaneously with high precision. By tuning the applied laser to an
      intermediate wavelength between transitions 4s_{1/2}->4p_{1/2} and 4s_{1/2}
      >4p_{3/2}, the sensitivity of the clock transition Stark shift to the oscillator
      strengths is greatly enhanced. Furthermore, with the measured magic wavelengths,
      we determine the ratio of the oscillator strengths with a deviation of less than
      0.5%. Our experimental method may be applied to measure magic wavelengths for
      other ion clock transitions. Promisingly, the measurement of these magic
      wavelengths paves the way to building all-optical trapped ion clocks.

PMID- 26196622
TI  - Scheme for Achieving a Topological Photonic Crystal by Using Dielectric Material.
AB  - We derive in the present work topological photonic states purely based on
      conventional dielectric material by deforming a honeycomb lattice of cylinders
      into a triangular lattice of cylinder hexagons. The photonic topology is
      associated with a pseudo-time-reversal (TR) symmetry constituted by the TR
      symmetry supported in general by Maxwell equations and the C_{6} crystal symmetry
      upon design, which renders the Kramers doubling in the present photonic system.
      It is shown explicitly for the transverse magnetic mode that the role of
      pseudospin is played by the angular momentum of the wave function of the out-of
      plane electric field. We solve Maxwell equations and demonstrate the new photonic
      topology by revealing pseudospin-resolved Berry curvatures of photonic bands and
      helical edge states characterized by Poynting vectors. 

PMID- 26196623
TI  - Brownian Motion of Molecular Probes in Supercooled Liquids.
AB  - When a supercooled liquid approaches glass transition, viscous flow slows down
      greatly, but often the Brownian motion of a molecular probe in the host liquid
      does not slow down as much, causing the Stokes-Einstein relation to fail by
      orders of magnitude. Here we formulate a theory that relates the Brownian motion
      of the probe to two concurrent processes in the host liquid: viscous flow and
      molecular hopping. Molecular hopping prevails over viscous flow when the probe is
      small and the temperature is low. Our theory generalizes the Stokes-Einstein
      relation and fits the experimental data remarkably well. 

PMID- 26196624
TI  - Weyl Points in Three-Dimensional Optical Lattices: Synthetic Magnetic Monopoles
      in Momentum Space.
AB  - We show that a Hamiltonian with Weyl points can be realized for ultracold atoms
      using laser-assisted tunneling in three-dimensional optical lattices. Weyl points
      are synthetic magnetic monopoles that exhibit a robust, three-dimensional linear
      dispersion, identical to the energy-momentum relation for relativistic Weyl
      fermions, which are not yet discovered in particle physics. Weyl semimetals are a
      promising new avenue in condensed matter physics due to their unusual properties
      such as the topologically protected "Fermi arc" surface states. However,
      experiments on Weyl points are highly elusive. We show that this elusive goal is
      well within experimental reach with an extension of techniques recently used in
      ultracold gases. 

PMID- 26196625
TI  - Antiferromagnetic Spinor Condensates in a Two-Dimensional Optical Lattice.
AB  - We experimentally demonstrate that spin dynamics and the phase diagram of spinor
      condensates can be conveniently tuned by a two-dimensional optical lattice. Spin
      population oscillations and a lattice-tuned separatrix in phase space are
      observed in every lattice where a substantial superfluid fraction exists. In a
      sufficiently deep lattice, we observe a phase transition from a longitudinal
      polar phase to a broken-axisymmetry phase in steady states of lattice-confined
      spinor condensates. The steady states are found to depend sigmoidally on the
      lattice depth and exponentially on the magnetic field. We also introduce a
      phenomenological model that semiquantitatively describes our data without
      adjustable parameters. 

PMID- 26196626
TI  - Damping of Long-Wavelength Collective Modes in Spinor Bose-Fermi Mixtures.
AB  - Using an effective field theory we describe the low energy bosonic excitations in
      a three-dimensional ultracold mixture of spin-1 bosons and spin-1/2 fermions. We
      establish an interesting fermionic excitation induced generic damping of the
      usual undamped long-wavelength bosonic collective Goldstone modes. Two states
      with bosons forming either a ferromagnetic or polar superfluid are studied. The
      linear dispersion of the bosonic Bogoliubov excitations is preserved with a
      renormalized sound velocity. For the polar superfluid we find both gapless modes
      (density and spin) are damped, whereas in the ferromagnetic superfluid we find
      the density (spin) mode is (not) damped. We find that this holds for any mixture
      of bosons and fermions that are coupled through at least a density-density
      interaction. In addition, we predict the existence of the Kohn anomaly in the
      bosonic excitation spectrum of Bose-Fermi mixtures. We discuss the implications
      of our many-body interaction results for experiments on Bose-Fermi mixtures. 

PMID- 26196627
TI  - The Principle of Independent Bond-Level Response: Tuning by Pruning to Exploit
      Disorder for Global Behavior.
AB  - We introduce a principle unique to disordered solids wherein the contribution of
      any bond to one global perturbation is uncorrelated with its contribution to
      another. Coupled with sufficient variability in the contributions of different
      bonds, this "independent bond-level response" paves the way for the design of
      real materials with unusual and exquisitely tuned properties. To illustrate this,
      we choose two global perturbations: compression and shear. By applying a bond
      removal procedure that is both simple and experimentally relevant to remove a
      very small fraction of bonds, we can drive disordered spring networks to both the
      incompressible and completely auxetic limits of mechanical behavior. 

PMID- 26196628
TI  - Specific Heat Anomaly in a Supercooled Liquid with Amorphous Boundary Conditions.
AB  - We study the specific heat of a model supercooled liquid confined in a spherical
      cavity with amorphous boundary conditions. We find the equilibrium specific heat
      has a cavity-size-dependent peak as a function of temperature. The cavity allows
      us to perform a finite-size scaling (FSS) analysis, which indicates that the peak
      persists at a finite temperature in the thermodynamic limit. We attempt to
      collapse the data onto a FSS curve according to different theoretical scenarios,
      obtaining reasonable results in two cases: a "not-so-simple" liquid with
      nonstandard values of the exponents alpha and nu, and random first-order theory,
      with two different length scales. 

PMID- 26196629
TI  - Transition from Order to Configurational Disorder for Surface Reconstructions on
      SrTiO_{3}(111).
AB  - There is growing interest in ternary oxide surfaces due to their role in areas
      ranging from substrates for low power electronics to heterogeneous catalysis.
      Descriptions of these surfaces to date focus on low-temperature explanations
      where enthalpy dominates, and less on the implications of configurational entropy
      at high temperatures. We report here the structure of three members of the n*n 
      (2<=n<=4) reconstructions of the strontium titanate (111) surface using a
      combination of transmission electron diffraction, density functional theory
      modeling, and scanning tunneling microscopy. The surfaces contain a mixture of
      the tetrahedral TiO_{4} units found on the (110) surface sitting on top of
      octahedral TiO_{5}[] (where [] is a vacant octahedral site), and TiO_{6} units in
      the second layer that are similar to those found on the (001) surface. We find
      clear evidence of a transition from the ordered enthalpy-dominated 3*3 and 4*4
      structures to a configurational entropy-dominated 2*2 structure that is formed at
      higher temperatures. This changes many aspects of how oxide surfaces should be
      considered, with significant implications for oxide growth. 

PMID- 26196630
TI  - Origin of Spinel Nanocheckerboards via First Principles.
AB  - Self-organizing nanocheckerboards have been experimentally fabricated in Mn-based
      spinels but have not yet been explained with first principles. Using density
      functional theory, we explain the phase diagram of the ZnMn_{x}Ga_{2-x}O_{4}
      system and the origin of nanocheckerboards. We predict total phase separation at
      zero temperature and then show the combination of kinetics, thermodynamics, and
      Jahn-Teller physics that generates the system's observed behavior. We find that
      the {011} surfaces are strongly preferred energetically, which mandates
      checkerboard ordering by purely geometrical considerations. 

PMID- 26196631
TI  - Interfacial Charge States in Graphene on SiC Studied by Noncontact Scanning
      Nonlinear Dielectric Potentiometry.
AB  - We investigate pristine and hydrogen-intercalated graphene synthesized on a 4H
      SiC(0001) substrate by using noncontact scanning nonlinear dielectric
      potentiometry (NC-SNDP). Permanent dipole moments are detected at the pristine
      graphene-SiC interface. These originate from the covalent bonds of carbon atoms
      of the so-called buffer layer to the substrate. Hydrogen intercalation at the
      interface eliminates these covalent bonds and the original quasi-(6*6)
      corrugation, which indicates the conversion of the buffer layer into a second
      graphene layer by the termination of Si bonds at the interface. NC-SNDP images
      suggest that a certain portion of the Si dangling bonds remains even after
      hydrogen intercalation. These bonds are thought to act as charged impurities
      reducing the carrier mobility in hydrogen-intercalated graphene on SiC. 

PMID- 26196632
TI  - Quantum Monte Carlo Calculations in Solids with Downfolded Hamiltonians.
AB  - We present a combination of a downfolding many-body approach with auxiliary-field
      quantum Monte Carlo (AFQMC) calculations for extended systems. Many-body
      calculations operate on a simpler Hamiltonian which retains material-specific
      properties. The Hamiltonian is systematically improvable and allows one to dial,
      in principle, between the simplest model and the original Hamiltonian. As a by
      product, pseudopotential errors are essentially eliminated using frozen orbitals
      constructed adaptively from the solid environment. The computational cost of the
      many-body calculation is dramatically reduced without sacrificing accuracy.
      Excellent accuracy is achieved for a range of solids, including semiconductors,
      ionic insulators, and metals. We apply the method to calculate the equation of
      state of cubic BN under ultrahigh pressure, and determine the spin gap in NiO, a
      challenging prototypical material with strong electron correlation effects.

PMID- 26196633
TI  - Normal-Mode Splitting in the Coupled System of Hybridized Nuclear Magnons and
      Microwave Photons.
AB  - In the weak ferromagnetic MnCO_{3} system, a low-frequency collective spin
      excitation (magnon) is the hybridized oscillation of nuclear and electron spins
      coupled through the hyperfine interaction. By using a split-ring resonator, we
      performed transmission spectroscopy measurements of the MnCO_{3} system and
      observed avoided crossing between the hybridized nuclear magnon mode and the
      resonator mode in the NMR-frequency range. The splitting strength is quite large
      due to the large spin density of ^{55}Mn, and the cooperativity value C=0.2 (the
      magnon-photon coupling parameter) is close to the conditions of strong coupling.
      The results reveal a new class of spin systems, in which the coupling between
      nuclear spins and photons is mediated by electron spins via the hyperfine
      interaction. 

PMID- 26196634
TI  - Electric-Field-Driven Resistive Switching in the Dissipative Hubbard Model.
AB  - We study how strongly correlated electrons on a dissipative lattice evolve out of
      equilibrium under a constant electric field, focusing on the extent of the linear
      regime and hysteretic nonlinear effects at higher fields. We access the
      nonequilibrium steady states, nonperturbatively in both the field and the
      electronic interactions, by means of a nonequilibrium dynamical mean-field theory
      in the Coulomb gauge. The linear response regime, limited by Joule heating,
      breaks down at fields much smaller than the quasiparticle energy scale. For large
      electronic interactions, strong but experimentally accessible electric fields can
      induce a resistive switching by driving the strongly correlated metal into a Mott
      insulator. We predict a nonmonotonic upper switching field due to an interplay of
      particle renormalization and the field-driven temperature. Hysteretic I-V curves
      suggest that the nonequilibrium current is carried through a spatially
      inhomogeneous metal-insulator mixed state. 

PMID- 26196635
TI  - Non-Fermi-Liquid Behavior and Anomalous Suppression of Landau Damping in Layered
      Metals Close to Ferromagnetism.
AB  - We analyze the low-energy physics of nearly ferromagnetic metals in two spatial
      dimensions using the functional renormalization group technique. We find a new
      low-energy fixed point, at which the fermionic (electronlike) excitations are non
      Fermi-liquid (z_{f}=13/10) and the magnetic fluctuations exhibit an anomalous
      Landau damping whose rate vanishes as Gamma_{q}~|q|^{3/5} in the low-|q| limit.
      We discuss this renormalization of the Landau-damping exponent, which is the
      major novel prediction of our work, and highlight the possible link between that
      renormalization and neutron-scattering data on UGe_{2} and related compounds.
      Implications of our analysis for YFe_{2}Al_{10} are also discussed. 

PMID- 26196636
TI  - Wess-Zumino-Witten Terms in Graphene Landau Levels.
AB  - We consider the interplay between the antiferromagnetic and Kekule valence bond
      solid orderings in the zero energy Landau levels of neutral monolayer and bilayer
      graphene. We establish the presence of Wess-Zumino-Witten terms between these
      orders: this implies that their quantum fluctuations are described by the
      deconfined critical theories of quantum spin systems. We present implications for
      experiments, including the possible presence of excitonic superfluidity in
      bilayer graphene. 

PMID- 26196637
TI  - Topological Crystalline Insulator Phase in Graphene Multilayers.
AB  - While the experimental progress on three dimensional topological insulators is
      rapid, the development of their 2D counterparts has been comparatively slow,
      despite their technological promise. The main reason is materials challenges of
      the to date only realizations of 2D topological insulators, in semiconductor
      quantum wells. Here we identify a 2D topological insulator in a material which
      does not face similar challenges and which is by now most widely available and
      well charaterized: graphene. For certain commensurate interlayer twists, graphene
      multilayers are insulators with sizable band gaps. We show that they are moreover
      in a topological phase protected by crystal symmetry. As its fundamental
      signature, this topological state supports one-dimensional boundary modes. They
      form low-dissipation quantum wires that can be defined purely electrostatically. 

PMID- 26196638
TI  - Tunable Spin-Qubit Coupling Mediated by a Multielectron Quantum Dot.
AB  - We present an approach for entangling electron spin qubits localized on spatially
      separated impurity atoms or quantum dots via a multielectron, two-level quantum
      dot. The effective exchange interaction mediated by the dot can be understood as
      the simplest manifestation of Ruderman-Kittel-Kasuya-Yosida exchange, and can be
      manipulated through gate voltage control of level splittings and tunneling
      amplitudes within the system. This provides both a high degree of tunability and
      a means for realizing high-fidelity two-qubit gates between spatially separated
      spins, yielding an experimentally accessible method of coupling donor electron
      spins in silicon via a hybrid impurity-dot system. 

PMID- 26196639
TI  - Double Path Interference and Magnetic Oscillations in Cooper Pair Transport
      through a Single Nanowire.
AB  - We show that the critical current of the Josephson junction consisting of
      superconducting electrodes coupled through a nanowire with two conductive
      channels can reveal the multiperiodic magnetic oscillations. The multiperiodicity
      originates from the quantum mechanical interference between the channels affected
      by both the strong spin-orbit coupling and the Zeeman interaction. This minimal
      two-channel model is shown to explain the complicated interference phenomena
      observed recently in Josephson transport through Bi nanowires. 

PMID- 26196640
TI  - Spin Pumping in Electrodynamically Coupled Magnon-Photon Systems.
AB  - We use electrical detection, in combination with microwave transmission, to
      investigate both resonant and nonresonant magnon-photon coupling at room
      temperature. Spin pumping in a dynamically coupled magnon-photon system is found
      to be distinctly different from previous experiments. Characteristic coupling
      features such as modes anticrossing, linewidth evolution, peculiar line shape,
      and resonance broadening are systematically measured and consistently analyzed by
      a theoretical model set on the foundation of classical electrodynamic coupling.
      Our experimental and theoretical approach paves the way for pursuing microwave
      coherent manipulation of pure spin current via the combination of spin pumping
      and magnon-photon coupling. 

PMID- 26196641
TI  - One-Third Magnetization Plateau with a Preceding Novel Phase in Volborthite.
AB  - We have synthesized high-quality single crystals of volborthite, a seemingly
      distorted kagome antiferromagnet, and carried out high-field magnetization
      measurements up to 74 T and ^{51}V NMR measurements up to 30 T. An extremely wide
      1/3 magnetization plateau appears above 28 T and continues over 74 T at 1.4 K,
      which has not been observed in previous studies using polycrystalline samples.
      NMR spectra reveal an incommensurate order (most likely a spin-density wave
      order) below 22 T and a simple spin structure in the plateau phase. Moreover, a
      novel intermediate phase is found between 23 and 26 T, where the magnetization
      varies linearly with magnetic field and the NMR spectra indicate an inhomogeneous
      distribution of the internal magnetic field. This sequence of phases in
      volborthite bears a striking similarity to those of frustrated spin chains with a
      ferromagnetic nearest-neighbor coupling J_{1} competing with an antiferromagnetic
      next-nearest-neighbor coupling J_{2}.

PMID- 26196642
TI  - Dispersionless Spin Waves and Underlying Field-Induced Magnetic Order in
      Gadolinium Gallium Garnet.
AB  - We report the results of neutron diffraction and inelastic neutron scattering on
      a powder sample of Gd_{3}Ga_{5}O_{12} at high magnetic fields. Analysis of the
      diffraction data shows that in high fields (B?1.8 T) the spins are not fully
      aligned, but are canted slightly as a result of the dipolar interaction. The
      magnetic phase for fields ?1.8 T is characterized by antiferromagnetic peaks at
      (210) and an incommensurate wave vector. The dominant contribution to inelastic
      scattering at large momentum transfers is from a band of almost dispersionless
      excitations. We show that these correspond to the spin waves localized on ten
      site rings, expected on the basis of nearest neighbor exchange interaction, and
      that the spectrum at high fields B?1.8 T is well described by a spin wave theory.

PMID- 26196643
TI  - Coherent Visible-Light-Generation Enhancement in Silicon-Based Nanoplasmonic
      Waveguides via Third-Harmonic Conversion.
AB  - We report visible third-harmonic conversion at lambda=517 nm in subwavelength
      silicon-based nanoplasmonic waveguides at an unprecedented conversion efficiency
      of 2.3*10^{-5}. This marks both the highest third-harmonic conversion efficiency
      in a silicon-based or nanoplasmonic structure and the smallest silicon waveguide
      structure demonstrated to date. The high conversion efficiency is attributed to
      tight electric field confinement and strong light-matter coupling arising from
      surface plasmon modes in the nanoplasmonic waveguide, enabling efficient
      nonlinear optical mixing over micrometer length scales. The nonresonant geometry
      of the waveguide enables the entire lambda=1550 nm femtosecond pulse spectrum to
      be converted to its third harmonic, which may be easily extended to the entire
      visible spectrum. We envisage that third-harmonic generation in silicon-based
      nanoplasmonic waveguides could provide a platform for integrated, broadband
      visible light sources and entangled triplet photons on future hybrid electronic
      silicon photonic chips.

PMID- 26196644
TI  - Spatially Resolved Thermodynamics of the Partially Ionized Exciton Gas in GaAs.
AB  - We report on the observation of macroscopic free exciton photoluminescence (PL)
      rings that appear in spatially resolved PL images obtained on a high purity GaAs
      sample. We demonstrate that a spatial temperature gradient in the photocarrier
      system, which is due to nonresonant optical excitation, locally modifies the
      population balance between free excitons and the uncorrelated electron-hole
      plasma described by the Saha equation and accounts for the experimentally
      observed nontrivial PL profiles. The exciton ring formation is a particularly
      instructive manifestation of the spatially dependent thermodynamics of a
      partially ionized exciton gas in a bulk semiconductor. 

PMID- 26196645
TI  - Highly Coherent Electron Beam from a Laser-Triggered Tungsten Needle Tip.
AB  - We report on a quantitative measurement of the spatial coherence of electrons
      emitted from a sharp metal needle tip. We investigate the coherence in
      photoemission triggered by a near-ultraviolet laser with a photon energy of 3.1
      eV and compare it to dc-field emission. A carbon nanotube is brought into close
      proximity to the emitter tip to act as an electrostatic biprism. From the
      resulting electron matter wave interference fringes, we deduce an upper limit of
      the effective source radius both in laser-triggered and dc-field emission mode,
      which quantifies the spatial coherence of the emitted electron beam. We obtain
      (0.80+/-0.05) nm in laser-triggered and (0.55+/-0.02) nm in dc-field emission
      mode, revealing that the outstanding coherence properties of electron beams from
      needle tip field emitters are largely maintained in laser-induced emission. In
      addition, the relative coherence width of 0.36 of the photoemitted electron beam
      is the largest observed so far. The preservation of electronic coherence during
      emission as well as ramifications for time-resolved electron imaging techniques
      are discussed.

PMID- 26196646
TI  - Boundary Condition in Liquid Thin Films Revealed through the Thermal Fluctuations
      of Their Free Surfaces.
AB  - We investigate the properties of nanometric liquid films with a new noninvasive
      technique. We measure the spontaneous thermal fluctuations of the free surfaces
      of liquids to probe their hydrodynamic boundary condition at a solid wall. The
      surface fluctuations of a silicon oil film could be described with a no-slip
      boundary condition for film thicknesses down to 20 nm. Oppositely, a 4 nm
      negative slip length had to be introduced to describe the behavior of n
      hexadecane, consistently with previous surface force apparatus data on the same
      system. Our results demonstrate that at vanishing flow a nanometric solidlike
      layer close to the wall may exist according to the nature of the liquid.

PMID- 26196647
TI  - Propagating Stress Waves During Epithelial Expansion.
AB  - Coordinated motion of cell monolayers during epithelial wound healing and tissue
      morphogenesis involves mechanical stress generation. Here we propose a model for
      the dynamics of epithelial expansion that couples mechanical deformations in the
      tissue to contractile activity and polarization in the cells. A new ingredient of
      our model is a feedback between local strain, polarization, and contractility
      that naturally yields a mechanism for viscoelasticity and effective inertia in
      the cell monolayer. Using a combination of analytical and numerical techniques,
      we demonstrate that our model quantitatively reproduces many experimental
      findings [Nat. Phys. 8, 628 (2012)], including the buildup of intercellular
      stresses, and the existence of traveling mechanical waves guiding the oscillatory
      monolayer expansion. 

PMID- 26196649
TI  - Two-Dimensional Clusters of Colloidal Spheres: Ground States, Excited States, and
      Structural Rearrangements.
AB  - We study experimentally what is arguably the simplest yet nontrivial colloidal
      system: two-dimensional clusters of six spherical particles bound by depletion
      interactions. These clusters have multiple, degenerate ground states whose
      equilibrium distribution is determined by entropic factors, principally the
      symmetry. We observe the equilibrium rearrangements between ground states as well
      as all of the low-lying excited states. In contrast to the ground states, the
      excited states have soft modes and low symmetry, and their occupation
      probabilities depend on the size of the configuration space reached through
      internal degrees of freedom, as well as a single "sticky parameter" encapsulating
      the depth and curvature of the potential. Using a geometrical model that accounts
      for the entropy of the soft modes and the diffusion rates along them, we
      accurately reproduce the measured rearrangement rates. The success of this model,
      which requires no fitting parameters or measurements of the potential, shows that
      the free-energy landscape of colloidal systems and the dynamics it governs can be
      understood geometrically. 

PMID- 26196648
TI  - Emergence and Persistence of Collective Cell Migration on Small Circular
      Micropatterns.
AB  - The spontaneous formation of vortices is a hallmark of collective cellular
      activity. Here, we study the onset and persistence of coherent angular motion as
      a function of the number of cells N confined in circular micropatterns. We find
      that the persistence of coherent angular motion increases with N but exhibits a
      pronounced discontinuity accompanied by a geometric rearrangement of cells to a
      configuration containing a central cell. Computer simulations based on a
      generalized Potts model reproduce the emergence of vortex states and show in
      agreement with experiment that their stability depends on the interplay of the
      spatial arrangement and internal polarization of neighboring cells. Hence, the
      distinct migrational states in finite size ensembles reveal significant insight
      into the local interaction rules guiding collective migration. 

PMID- 26196650
TI  - Implicit body representations and tactile spatial remapping.
AB  - To perceive the location of a tactile stimulus in external space (external
      tactile localisation), information about the location of the stimulus on the skin
      surface (tactile localisation on the skin) must be combined with proprioceptive
      information about the spatial location of body parts (position sense)--a process
      often referred to as 'tactile spatial remapping'. Recent research has revealed
      that both of these component processes rely on highly distorted implicit body
      representations. For example, on the dorsal hand surface position sense relies on
      a squat, wide hand representation. In contrast, tactile localisation on the same
      skin surface shows large biases towards the knuckles. These distortions can be
      seen as behavioural 'signatures' of these respective perceptual processes. Here,
      we investigated the role of implicit body representation in tactile spatial
      remapping by investigating whether the distortions of each of the two component
      processes (tactile localisation and position sense) also appear when participants
      localise the external spatial location of touch. Our study reveals strong
      distortions characteristic of position sense (i.e., overestimation of distances
      across vs along the hand) in tactile spatial remapping. In contrast, distortions
      characteristic of tactile localisation on the skin (i.e., biases towards the
      knuckles) were not apparent in tactile spatial remapping. These results
      demonstrate that a common implicit hand representation underlies position sense
      and external tactile localisation. Furthermore, the present findings imply that
      tactile spatial remapping does not require mapping the same signals in a frame of
      reference centred on a specific body part.

PMID- 26196651
TI  - RECURRENT SUBRETINAL HEMORRHAGE ASSOCIATED WITH RIVAROXABAN ANTICOAGULATION.
AB  - PURPOSE: To report a case of spontaneous recurrent significant subretinal
      hemorrhage in a patient on rivaroxaban (Xarelto). METHODS: A case report of a 63
      year-old man on rivaroxaban with peripapillary choroidal neovascular membrane and
      macula involving subretinal hemorrhage. RESULTS: Improvement in visual acuity
      from 20/200 to 20/30 and restoration of foveal contour after pneumatic
      displacement of hemorrhage with C3F8 gas and subsequent treatment with
      ranibizumab. CONCLUSION: The authors report a case of recurrent subretinal
      hemorrhage associated with rivaroxaban use. Pneumatic displacement and subsequent
      treatment of choroidal neovascular membrane with intravitreal ranibizumab
      improved visual acuity.

PMID- 26196652
TI  - Risk of mortality in relation to an updated classification of left ventricular
      geometric abnormalities in a general population: the Pamela study.
AB  - AIM: We estimated the risk of cardiovascular and all-cause mortality associated
      with left ventricular geometric patterns, as defined by a new classification
      system proposed by the Dallas Heart Study, in 1716 representatives of the general
      population of Monza enrolled in the Pressioni Monitorate e Loro Associazioni
      (PAMELA) study. METHODS: Cut-points for abnormal left ventricular geometric
      patterns were derived from reference values of the healthy fraction of the PAMELA
      population by combining left ventricular mass (LVM) index, left ventricular
      diameter and relative wall thickness. Death certificates were collected over an
      average 211 months follow-up period. RESULTS: During follow-up, 89 fatal
      cardiovascular events and 264 all-cause deaths were recorded. Concentric
      remodelling was the most common left ventricular geometric abnormality (9.4%)
      followed by eccentric nondilated left ventricular hypertrophy (LVH) (6.3%),
      concentric LVH (4.6%) and eccentric dilated LVH (3.5%). Compared with normal left
      ventricular geometry, concentric LVH [hazard ratio 2.20, 95% confidence interval
      (95% CI) 1.44-3.37, P < 0.0003], eccentric dilated LVH (hazard ratio 1.90, 95% CI
      1.17-3.08, P = 0.009) and eccentric nondilated LVH (hazard ratio 1.57, 95% CI
      1.07-2.31, P = 0.02) predicted the risk of cardiovascular mortality, after
      adjustment for baseline covariates, including ambulatory blood pressure. Similar
      findings were observed for all-cause mortality. Only concentric LVH maintained a
      significant prognostic value for both outcomes after adjustment for baseline
      differences in LVM index. CONCLUSION: The new classification system of left
      ventricular geometric patterns may improve mortality risk stratification in a
      general population. The risk is markedly dependent on LVM values; only concentric
      LVH provides a prognostic information beyond that conveyed by cardiac mass.

PMID- 26196653
TI  - Exploiting Distributed, Heterogeneous and Sensitive Data Stocks while Maintaining
      the Owner's Data Sovereignty.
AB  - BACKGROUND: To achieve statistical significance in medical research, biological
      or data samples from several bio- or databanks often need to be complemented by
      those of other institutions. For that purpose, IT-based search services have been
      established to locate datasets matching a given set of criteria in databases
      distributed across several institutions. However, previous approaches require
      data owners to disclose information about their samples, raising a barrier for
      their participation in the network. OBJECTIVE: To devise a method to search
      distributed databases for datasets matching a given set of criteria while fully
      maintaining their owner's data sovereignty. METHODS: As a modification to
      traditional federated search services, we propose the decentral search, which
      allows the data owner a high degree of control. Relevant data are loaded into
      local bridgeheads, each under their owner's sovereignty. Researchers can
      formulate criteria sets along with a project proposal using a central search
      broker, which then notifies the bridgeheads. The criteria are, however, treated
      as an inquiry rather than a query: Instead of responding with results,
      bridgeheads notify their owner and wait for his/her decision regarding whether
      and what to answer based on the criteria set, the matching datasets and the
      specific project proposal. Without the owner's explicit consent, no data leaves
      his/her institution. RESULTS: The decentral search has been deployed in one of
      the six German Centers for Health Research, comprised of eleven university
      hospitals. In the process, compliance with German data protection regulations has
      been confirmed. The decentral search also marks the centerpiece of an open source
      registry software toolbox aiming to build a national registry of rare diseases in
      Germany. CONCLUSIONS: While the sacrifice of real-time answers impairs some use
      cases, it leads to several beneficial side effects: improved data protection due
      to data parsimony, tolerance for incomplete data schema mappings and flexibility
      with regard to patient consent. Most importantly, as no datasets ever leave their
      institution, owners can reject projects without facing potential peer pressure.
      By its lower barrier for participation, a decentral search service is likely to
      attract a larger number of partners and to bring a researcher into contact with
      the right potential partners.

PMID- 26196654
TI  - Headspace versus direct immersion solid phase microextraction in complex
      matrixes: investigation of analyte behavior in multicomponent mixtures.
AB  - This work aims to investigate the behavior of analytes in complex mixtures and
      matrixes with the use of solid-phase microextraction (SPME). Various factors that
      influence analyte uptake such as coating chemistry, extraction mode, the
      physicochemical properties of analytes, and matrix complexity were considered. At
      first, an aqueous system containing analytes bearing different hydrophobicities,
      molecular weights, and chemical functionalities was investigated by using
      commercially available liquid and solid porous coatings. The differences in the
      mass transfer mechanisms resulted in a more pronounced occurrence of coating
      saturation in headspace mode. Contrariwise, direct immersion extraction minimizes
      the occurrence of artifacts related to coating saturation and provides enhanced
      extraction of polar compounds. In addition, matrix-compatible PDMS-modified solid
      coatings, characterized by a new morphology that avoids coating fouling, were
      compared to their nonmodified analogues. The obtained results indicate that PDMS
      modified coatings reduce artifacts associated with coating saturation, even in
      headspace mode. This factor, coupled to their matrix compatibility, make the use
      of direct SPME very practical as a quantification approach and the best choice
      for metabolomics studies where wide coverage is intended. To further understand
      the influence on analyte uptake on a system where additional interactions occur
      due to matrix components, ex vivo and in vivo sampling conditions were simulated
      using a starch matrix model, with the aim of mimicking plant-derived materials.
      Our results corroborate the fact that matrix handling can affect analyte/matrix
      equilibria, with consequent release of high concentrations of previously bound
      hydrophobic compounds, potentially leading to coating saturation. Direct
      immersion SPME limited the occurrence of the artifacts, which confirms the
      suitability of SPME for in vivo applications. These findings shed light into the
      implementation of in vivo SPME strategies in quantitative metabolomics studies of
      complex plant-based systems. 

PMID- 26196655
TI  - Symptoms of multiple sclerosis during use of combined hormonal contraception.
AB  - OBJECTIVE: The incidence and disease course of multiple sclerosis (MS) is
      influenced by sex steroids, and several studies have shown less disease activity
      during high estrogen states. We have previously shown variation in symptom
      experience related to the estrogen/progestogen phase in women using combined
      hormonal contraceptives (CHC) in a small sample. The aim of this study was to
      confirm these results in a larger sample. STUDY DESIGN: Self-assessment of
      symptoms of MS in relation to CHC cycle by 22 female MS patients. A symptom diary
      based on a validated instrument for cyclical symptoms was used. Mean symptom
      scores for high and low estrogen/progestogen phases were compared. RESULTS: The
      women scored four out of ten symptoms significantly higher during the pill-free
      week than during the CHC phase (p<.05). CONCLUSION: Women with MS report more
      pronounced symptoms during the pill-free, low-estrogen/progestogen phase of CHC
      use. Future studies should investigate, with a prospective, controlled design,
      the effects that continuous-use regimens of CHC have in women with MS.

PMID- 26196656
TI  - Nerve-sparing abdominal radical trachelectomy: a novel concept to preserve
      uterine branches of pelvic nerves.
AB  - OBJECTIVES: Nerve-sparing techniques to avoid bladder dysfunction in abdominal
      radical hysterectomy have been established during the past two decades, and they
      have been applied to radical trachelectomy. Although trachelectomy retains the
      uterine corpus, no report mentions the preservation of uterine branches of pelvic
      nerves. The aim of the present study was to introduce and discuss our unique
      concept for preserving them. STUDY DESIGN AND RESULTS: Four cases with FIGO stage
      Ia2-Ib1 cervical cancer, in which preservation of uterine branches of the pelvic
      nerves was attempted, are presented. Operative procedures basically followed the
      previously reported standard approaches for nerve-sparing radical hysterectomy or
      trachelectomy, except for some points. Before resection of the sacrouterine
      ligament, the hypogastric nerve was first identified and translocated laterally.
      Subsequently, the uterine branches of the pelvic nerve were identified as a
      continuation of the hypogastric nerve and could be scooped with forceps by
      detachment of the surrounding connective tissues. Further detachment toward the
      uterine corpus enabled them to be completely separated from the cervix. This
      separation was extended up to the level of the junction of the upper and lower
      branches of the uterine artery. Thereafter, standard resection of the parametrium
      and paracolpium was performed, followed by cervical resection when it was
      confirmed that the isolated uterine branches of the pelvic nerves were safely
      translocated and preserved. There were no recurrences of cancer in these
      patients. CONCLUSIONS: Uterine branches of autonomic nerves can be safely
      preserved, and the procedure may be considered one of the nerve-sparing
      techniques for radical abdominal trachelectomy, which may hopefully improve the
      reproductive outcomes of this operation, although it needs to be evaluated with
      more patients.

PMID- 26196657
TI  - Smoking cessation and the cardiovascular patient.
AB  - PURPOSE OF REVIEW: Smoking remains the leading cause of preventable morbidity and
      mortality. Our review highlights research from 2013 to 2015 on the treatment of
      cigarette smoking, with a focus on heart patients and cardiovascular outcomes.
      RECENT FINDINGS: Seeking to maximize the reach and effectiveness of existing
      cessation medications, current tobacco control research has demonstrated the
      safety and efficacy of combination treatment, extended use, reduce-to-quit
      strategies, and personalized approaches to treatment matching. Further, cytisine
      has gained interest as a lower-cost strategy for addressing the global tobacco
      epidemic. On the harm reduction front, snus and electronic nicotine delivery
      systems are being widely distributed and promoted with major gaps in knowledge of
      the safety of long-term and dual use. Quitlines, comparable in outcome to in
      person treatment, make cessation counseling available on a national scale, though
      use rates remain relatively low. Employee reward programs are gaining attention
      given the high costs of tobacco use to employers; sustaining quit rates
      postpayment, however, has proven challenging. SUMMARY: Evidence-based cessation
      treatments exist. Broader dissemination, adoption, and implementation are key to
      addressing the tobacco epidemic. The cardiology team has a professional
      obligation to advance tobacco control efforts and can play an important role in
      achieving a smoke-free future.

PMID- 26196658
TI  - Differentiating the athlete's heart from hypertrophic cardiomyopathy.
AB  - PURPOSE OF REVIEW: Exercise-induced cardiac remodeling (EICR), or athlete's
      heart, refers to the cardiac structural and functional adaptations to exercise
      training. Although the degree of physiological left ventricular hypertrophy (LVH)
      is typically mild in trained athletes, in some LVH is substantial enough to
      prompt concern for hypertrophic cardiomyopathy (HCM). This review summarizes the
      available imaging tools to help make this important clinical distinction. RECENT
      FINDINGS: Advanced echocardiographic techniques (tissue and Doppler and speckle
      tracking) and cardiac magnetic resonance imaging are being investigated to aid in
      the differentiation of EICR and HCM in 'gray-zone' hypertrophy cases. Higher
      early diastolic (E') velocity by tissue Doppler imaging has been documented in
      athletes. HCM patients have been found to have lower global longitudinal strain
      (GLS) when compared with athletes with LVH. Analysis of twisting and untwisting
      of the LV with speckle tracking may also help distinguish athlete's heart from
      HCM. Studies of the expected degree and time course of LVH regression after
      exercise cessation (in the setting of prescribed detraining) are needed as this
      may be a useful adjunct to determine the cause of LVH in particularly challenging
      cases. SUMMARY: Ongoing research with novel imaging techniques continues to
      improve the ability to distinguish athlete's heart from HCM in situations of
      'gray-zone' hypertrophy.

PMID- 26196659
TI  - Using the concept of ideal cardiovascular health to measure population health: a
      review.
AB  - PURPOSE OF REVIEW: This article describes the recent literature from January 2014
      to March 2015 examining the cardiovascular health of populations using the
      concept of ideal cardiovascular health with a particular focus on cardiovascular
      health in different countries and the association with subclinical markers of
      cardiovascular disease (CVD). RECENT FINDINGS: The relatively new concept of
      ideal cardiovascular health, based on the presence of seven healthy behaviours
      and factors including nonsmoking, active physical activity, healthy diet, low
      body mass index, low blood pressure, glucose, and cholesterol, can be used to
      assess a population's health status and develop an understanding of how
      cardiovascular health is associated with biological disease processes and
      clinical outcomes such as CVD incidence and mortality. Recent studies have
      adapted the American Heart Association definition of ideal cardiovascular health
      to fit the available data in different countries and have shown that the
      prevalence of ideal cardiovascular health is low in populations worldwide,
      including North America, Europe, Asia, and the Middle East. Recent studies have
      also uncovered strong associations between ideal cardiovascular health metrics
      and subclinical markers for CVD such as coronary artery calcification, carotid
      intima-media thickness, and pulse wave velocity. SUMMARY: A number of studies
      have demonstrated the low prevalence of ideal cardiovascular health in several
      countries and a strong relationship with subclinical CVD and biomarkers. The
      association with subclinical markers for CVD provides some evidence of the
      intermediary biological pathways through which ideal cardiovascular health
      results in a lower incidence of CVD and highlights the importance of improving
      cardiovascular health metrics in the general population.

PMID- 26196660
TI  - Use of the RSA/RCOD Index to Identify Training Priority in Soccer Players.
AB  - The use of RSA/RCOD index indicates the repeated change-of-direction (RCOD)
      performance relative to the repeated-sprint ability (RSA) and provides a
      standardized approach to prioritize training needs for RSA and RCOD. To compare
      the RSA/RCOD index among different age groups, RSA and RCOD were measured from 20
      under-16 players (U16), 20 under-19 players (U19), and 17 first-team professional
      players (PRO) from a football (soccer) club that has regular participation in the
      UEFA Champions League. Each player performed the RSA and RCOD tests, during which
      the fastest time (FT), average time (AT), total time (TT), and percentage
      decrement score (%Dec) were recorded. No significant differences were found in
      RSA/RCOD index-FT, AT, TT, and %Dec among the 3 groups (p > 0.05) and between U19
      and PRO in all RSA and RCOD measures (p > 0.05). Most values of RSA/RCOD index
      were 0.51 among the U16, U19, and PRO groups. Moreover, we concluded that the
      RSA/RCOD index might not be further changed after 16 years of age unless specific
      training programs for RSA and RCOD are prescribed. Therefore, this study provides
      an empirical case, and coaches can establish the RSA/RCOD index value relevant to
      their training system and monitor players' training needs of RSA and RCOD in a
      longer term.

PMID- 26196661
TI  - Relationship Between Accelerometer Load, Collisions, and Repeated High-Intensity
      Effort Activity in Rugby League Players.
AB  - Triaxial accelerometers have been critical in providing information on the high
      acceleration, low-velocity movements that occur in team sports. In addition,
      these sensors have proven to be useful in quantifying the activities that do not
      involve the vertical acceleration associated with locomotion (e.g., tackling, on
      ground wrestling, and grappling). This study investigated the relationship
      between Player Load (PL), 2D Player Load (2DPL), and Player Load Slow (PL Slow),
      collisions, and repeated high-intensity effort (RHIE) activity in rugby league
      players. One hundred and eighty-two rugby league players (age, 24.3 +/- 3.3
      years) participated in this study. Movement was recorded using a global
      positioning system unit sampling at 10 Hz and triaxial accelerometer sampling at
      100 Hz. Analysis was completed during 26 matches (totaling 386 appearances).
      Pearson product-moment correlation coefficients were used to determine
      relationships between PL, 2DPL, and PL Slow and total collisions and RHIE
      activity. When all players were considered, weak relationships were found between
      PL and the number of collisions and RHIE bouts performed. However, PL was
      strongly associated (p <= 0.05) with total distance, low-speed activity, high
      speed running distance, total collisions, and the number of RHIE bouts for
      forwards and hookers. Weak and typically insignificant relationships were found
      between PL, 2DPL, and PL Slow and the number of collisions and RHIE bouts
      performed by the adjustables and outside backs positional groups. The
      relationships between PL and the number of collisions and RHIE bouts are stronger
      in positions where contact and repeated-effort demands are high. From a practical
      perspective, these results suggest that PL, 2DPL, and PL Slow offer useful "real
      time" measures of collision and RHIE activity, particularly in forwards and
      hookers, to inform interchange strategies and ensure players are training at an
      adequate intensity.

PMID- 26196662
TI  - Muscular Grip Strength Estimates of the U.S. Population from the National Health
      and Nutrition Examination Survey 2011-2012.
AB  - The purposes of this study were to use the National Health and Nutrition
      Examination Study (2011-12) data to determine nationally representative combined
      handgrip strength ranges and percentile information by sex and age group, examine
      trends in strength across age by sex, and to determine the relative proportion of
      children and adults falling into established health benefit zones (HBZ). Results
      indicate that mean strength was greater among men than women and increased
      linearly for children and in a quadratic fashion among adults for both sexes.
      Grip strength peaked in the 30- to 39-year age group for both men (216.4 lbs) and
      women (136.5 lbs) with subsequent age groups showing gradual decline, p < 0.0001.
      Relative and absolute increases in grip strength were greater for men than for
      women, but relative decrease from peak strength was less among women than men.
      Although absolute strength was greater among men than women, HBZ data indicated
      that a higher percentage of men than women overall and at each age group fell
      into the needs improvement zone, with differences particularly pronounced during
      adolescence and older adulthood. These data provide the first nationally
      representative population estimates of combined handgrip strength and percentile
      information from childhood through senescence and suggest consideration of HBZ
      information in conjunction with grip strength to improve surveillance data
      interpretation and intervention planning.

PMID- 26196663
TI  - Precursors of Halobenzoquinones and Their Removal During Drinking Water Treatment
      Processes.
AB  - Halobenzoquinones (HBQs) widely occur in drinking water treatment plant (DWTP)
      effluents; however, HBQ precursors and their removal by treatments remain
      unclear. Thus, we have investigated HBQ precursors in plant influents and their
      removal by each treatment before chlorination in nine DWTPs. The levels of HBQ
      precursors were determined using formation potential (FP) tests for 2,6-dichloro
      1,4-benzoquinone (DCBQ), 2,3,6-trichloro-1,4-benzoquinone (TCBQ), 2,6-dichloro-3
      methyl-1,4-benzoquinone (DCMBQ), and 2,6-dibromo-1,4-benzoquinone (DBBQ). HBQ
      precursors were present in all plant influents. DCBQ precursors were the most
      abundant (DCBQ FP up to 205 ng/L). Coagulation removed dissolved organic carbon
      (DOC) (up to 56%) and HBQ precursors (up to 39% for DCBQ). The level of removal
      of DOC was significantly greater than the level of removal of HBQ FP, suggesting
      that organic matter removed by coagulation had a high proportion of non-HBQ
      precursor material. Granular activated carbon (GAC) decreased the level of HBQ
      FPs by 10-20%, where DOC removal was only 0.2-4.7%, suggesting that the GAC was
      not in the adsorption mode and biodegradation of HBQ precursors may have been
      occurring. Ozonation destroyed/transformed HBQ FPs by 10-30%, whereas
      anthracite/sand filtration and UV irradiation appeared to have no impact. The
      results demonstrated that the combined treatments did not substantially reduce
      HBQ precursor levels in water.

PMID- 26196664
TI  - Effect of Polymer Micelles on Antifungal Activity of Geranylorcinol Compounds
      against Botrytis cinerea.
AB  - Herein, we explore the potential use of two micelle-forming block copolymers,
      i.e., Pluronic F-127 and poly(ethylene oxide)-b-poly(caprolactone), for
      application of fungicide agents. The polymer effect on the in vitro fungicide
      activity of a series of geranyl orcinol derivatives against Botrytis cinerea has
      been assessed. The results show that, for all test compounds, the incorporation
      into micelles, formed by Pluronic F-127, produces a great enhancement of the
      inhibitory effect on the growth of B. cinerea. For some compounds, at the lowest
      tested concentration (50 ppm), the percentage of inhibition increases
      significantly (from 0-10 to 80-90%) when the application is made using a polymer
      solution instead of an ethanol/water mixture. The synthesis and structural
      determination of a series of eight geranylphenols/diacetates, which were used as
      fungicide agents, are also discussed. These results suggest that polymer micelles
      are promising systems for application of crop-protecting agents. 

PMID- 26196667
TI  - Principal components analysis of reward prediction errors in a reinforcement
      learning task.
AB  - Models of reinforcement learning represent reward and punishment in terms of
      reward prediction errors (RPEs), quantitative signed terms describing the degree
      to which outcomes are better than expected (positive RPEs) or worse (negative
      RPEs). An electrophysiological component known as feedback related negativity
      (FRN) occurs at frontocentral sites 240-340ms after feedback on whether a reward
      or punishment is obtained, and has been claimed to neurally encode an RPE. An
      outstanding question however, is whether the FRN is sensitive to the size of both
      positive RPEs and negative RPEs. Previous attempts to answer this question have
      examined the simple effects of RPE size for positive RPEs and negative RPEs
      separately. However, this methodology can be compromised by overlap from
      components coding for unsigned prediction error size, or "salience", which are
      sensitive to the absolute size of a prediction error but not its valence. In our
      study, positive and negative RPEs were parametrically modulated using both reward
      likelihood and magnitude, with principal components analysis used to separate out
      overlying components. This revealed a single RPE encoding component responsive to
      the size of positive RPEs, peaking at ~330ms, and occupying the delta frequency
      band. Other components responsive to unsigned prediction error size were shown,
      but no component sensitive to negative RPE size was found.

PMID- 26196666
TI  - Resting spontaneous activity in the default mode network predicts performance
      decline during prolonged attention workload.
AB  - After continuous and prolonged cognitive workload, people typically show reduced
      behavioral performance and increased feelings of fatigue, which are known as
      "time-on-task (TOT) effects". Although TOT effects are pervasive in modern life,
      their underlying neural mechanisms remain elusive. In this study, we induced TOT
      effects by administering a 20-min continuous psychomotor vigilance test (PVT) to
      a group of 16 healthy adults and used resting-state blood oxygen level-dependent
      (BOLD) functional magnetic resonance imaging (fMRI) to examine spontaneous brain
      activity changes associated with fatigue and performance. Behaviorally, subjects
      displayed robust TOT effects, as reflected by increasingly slower reaction times
      as the test progressed and higher self-reported mental fatigue ratings after the
      20-min PVT. Compared to pre-test measurements, subjects exhibited reduced
      amplitudes of low-frequency fluctuation (ALFF) in the default mode network (DMN)
      and increased ALFF in the thalamus after the test. Subjects also exhibited
      reduced anti-correlations between the posterior cingulate cortex (PCC) and right
      middle prefrontal cortex after the test. Moreover, pre-test resting ALFF in the
      PCC and medial prefrontal cortex (MePFC) predicted subjects' subsequent
      performance decline; individuals with higher ALFF in these regions exhibited more
      stable reaction times throughout the 20-min PVT. These results support the
      important role of both task-positive and task-negative networks in mediating TOT
      effects and suggest that spontaneous activity measured by resting-state BOLD fMRI
      may be a marker of mental fatigue. 

PMID- 26196665
TI  - Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1.
AB  - BACKGROUND: Effective treatment for hepatitis C virus (HCV) in patients
      coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet
      medical need. METHODS: We conducted a multicenter, single-group, open-label study
      involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an
      antiretroviral regimen of tenofovir and emtricitabine with efavirenz,
      rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor,
      and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose
      combination for 12 weeks. The primary end point was a sustained virologic
      response at 12 weeks after the end of therapy. RESULTS: Of the 335 patients
      enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had
      cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12
      weeks after the end of therapy (95% confidence interval [CI], 93 to 98),
      including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96%
      (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in
      those with HCV genotype 4. Rates of sustained virologic response were similar
      regardless of previous treatment or the presence of cirrhosis. Of the 13 patients
      who did not have a sustained virologic response, 10 had a relapse after the end
      of treatment. No patient had confirmed HIV-1 virologic rebound. The most common
      adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient
      discontinued treatment because of adverse events. CONCLUSIONS: Ledipasvir and
      sofosbuvir for 12 weeks provided high rates of sustained virologic response in
      patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead
      Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.).

PMID- 26196668
TI  - In vivo characterization of the connectivity and subcomponents of the human
      globus pallidus.
AB  - Projections from the substantia nigra and striatum traverse through the pallidum
      on the way to their targets. To date, in vivo characterization of these pathways
      remains elusive. Here we used high angular resolution diffusion imaging (N=138)
      to study the characteristics and structural subcompartments of the human
      pallidum. Our central result shows that the diffusion orientation distribution
      functions within the pallidum are asymmetrically oriented in a dorsal to
      dorsolateral direction, consistent with the orientation of underlying fiber
      systems. We also observed systematic differences in the diffusion signal between
      the two pallidal segments. Compared to the outer pallidal segment, the internal
      segment has more peaks in the diffusion orientation distribution and stronger
      anisotropy in the primary fiber direction, consistent with known cellular
      differences between the underlying nuclei. These differences in orientation,
      complexity, and degree of anisotropy are sufficiently robust to automatically
      segment the pallidal nuclei using diffusion properties. We characterize these
      patterns in one data set using diffusion spectrum imaging and replicate in a
      separate sample of subjects imaged using multi-shell imaging, highlighting the
      reliability of these diffusion patterns within pallidal nuclei. Thus the gray
      matter diffusion signal can be useful as an in vivo measure of the collective
      efferent pathways running through the human pallidum. 

PMID- 26196670
TI  - Geographic Distribution and Expansion of Human Lyme Disease, United States.
AB  - Lyme disease occurs in specific geographic regions of the United States. We
      present a method for defining high-risk counties based on observed versus
      expected number of reported human Lyme disease cases. Applying this method to
      successive periods shows substantial geographic expansion of counties at high
      risk for Lyme disease. 

PMID- 26196669
TI  - Affective state and locus of control modulate the neural response to threat.
AB  - The ability to regulate the emotional response to threat is critical to healthy
      emotional function. However, the response to threat varies considerably from
      person-to-person. This variability may be partially explained by differences in
      emotional processes, such as locus of control and affective state, which vary
      across individuals. Although the basic neural circuitry that mediates the
      response to threat has been described, the impact individual differences in
      affective state and locus of control have on that response is not well
      characterized. Understanding how these factors influence the neural response to
      threat would provide new insight into processes that mediate emotional function.
      Therefore, the present study used a Pavlovian conditioning procedure to
      investigate the influence individual differences in locus of control, positive
      affect, and negative affect have on the brain and behavioral responses to
      predictable and unpredictable threats. Thirty-two healthy volunteers participated
      in a fear conditioning study in which predictable and unpredictable threats
      (i.e., unconditioned stimulus) were presented during functional magnetic
      resonance imaging (fMRI). Locus of control showed a linear relationship with
      learning-related ventromedial prefrontal cortex (PFC) activity such that the more
      external an individual's locus of control, the greater their differential
      response to predictable versus unpredictable threat. In addition, positive and
      negative affectivity showed a curvilinear relationship with dorsolateral PFC,
      dorsomedial PFC, and insula activity, such that those with high or low
      affectivity showed reduced regional activity compared to those with an
      intermediate level of affectivity. Further, activity within the PFC, as well as
      other regions including the amygdala, were linked with the peripheral emotional
      response as indexed by skin conductance and electromyography. The current
      findings demonstrate that the neural response to threat within brain regions that
      mediate the peripheral emotional response is modulated by an individual's
      affective state as well as their perceptions of an event's causality. 

PMID- 26196671
TI  - Elastomeric Polymer Multilayer Thin Film with Sustainable Gas Barrier at High
      Strain.
AB  - Most gas barrier thin films suffer from cracking or plastic deformation when
      stretched, leading to significant loss of barrier. In an effort to make a
      stretchable gas barrier, which maintains low permeability when exposed to cyclic
      strain, we prepared layer-by-layer assemblies of tannic acid (TA) and
      poly(ethylene oxide) (PEO). A 40-bilayer (344 nm-thick) TA/PEO assembly
      maintained its oxygen transmission rate (6X lower than the 1.6 mm-thick rubber
      substrate) after being stretched 100%. This submicron coating maintains a barrier
      4X lower than the thick rubber substrate even after being strained 20X at 100%.
      These highly elastomeric assemblies are potentially useful for light-weighting
      inflatable devices. 

PMID- 26196672
TI  - Immortalisation with hTERT Impacts on Sulphated Glycosaminoglycan Secretion and
      Immunophenotype in a Variable and Cell Specific Manner.
AB  - BACKGROUND: Limited options for the treatment of cartilage damage have driven the
      development of tissue engineered or cell therapy alternatives reliant on ex vivo
      cell expansion. The study of chondrogenesis in primary cells is difficult due to
      progressive cellular aging and senescence. Immortalisation via the reintroduction
      of the catalytic component of telomerase, hTERT, could allow repeated,
      longitudinal studies to be performed while bypassing senescent phenotypes.
      METHODS: Three human cell types: bone marrow-derived stromal cells (BMA13),
      embryonic stem cell-derived (1C6) and chondrocytes (OK3) were transduced with
      hTERT (BMA13H, 1C6H and OK3H) and proliferation, surface marker expression and
      tri-lineage differentiation capacity determined. The sulphated glycosaminoglycan
      (sGAG) content of the monolayer and spent media was quantified in maintenance
      media (MM) and pro-chondrogenic media (PChM) and normalised to DNA. RESULTS:
      hTERT expression was confirmed in transduced cells with proliferation enhancement
      in 1C6H and OK3H cells but not BMA13H. All cells were negative for leukocyte
      markers (CD19, CD34, CD45) and CD73 positive. CD14 was expressed at low levels on
      OK3 and OK3H and HLA-DR on BMA13 (84.8%). CD90 was high for BMA13 (84.9%) and OK3
      (97.3%) and moderate for 1C6 (56.7%), expression was reduced in BMA13H (33.7%)
      and 1C6H (1.6%). CD105 levels varied (BMA13 87.7%, 1C6 8.2%, OK3 43.3%) and
      underwent reduction in OK3H (25.1%). 1C6 and BMA13 demonstrated osteogenic and
      adipogenic differentiation but mineralised matrix and lipid accumulation appeared
      reduced post hTERT transduction. Chondrogenic differentiation resulted in
      increased monolayer-associated sGAG in all primary cells and 1C6H (p<0.001), and
      BMA13H (p<0.05). In contrast OK3H demonstrated reduced monolayer-associated sGAG
      in PChM (p<0.001). Media-associated sGAG accounted for >=55% (PChM-1C6) and >=74%
      (MM-1C6H). CONCLUSION: In conclusion, hTERT transduction could, but did not
      always, prevent senescence and cell phenotype, including differentiation
      potential, was affected in a variable manner. As such, these cells are not a
      direct substitute for primary cells in cartilage regeneration research.

PMID- 26196675
TI  - Correction: Increased Functional Connectivity between Prefrontal Cortex and
      Reward System in Pathological Gambling.

PMID- 26196674
TI  - The Interferon-Inducible Mouse Apolipoprotein L9 and Prohibitins Cooperate to
      Restrict Theiler's Virus Replication.
AB  - Apolipoprotein L9b (Apol9b) is an interferon-stimulated gene (ISG) that has
      antiviral activity and is weakly expressed in primary mouse neurons as compared
      to other cell types. Here, we show that both Apol9 isoforms (Apol9b and Apol9a)
      inhibit replication of Theiler's murine encephalomyelitis virus (TMEV) but not
      replication of vesicular stomatitis virus (VSV), Murid herpesvirus-4 (MuHV-4), or
      infection by a lentiviral vector. Apol9 genes are strongly expressed in mouse
      liver and, to a lesser extent, in pancreas, adipose tissue and intestine. Their
      expression is increased by type I interferon and viral infection. In contrast to
      genuine apolipoproteins that are involved in lipid transport, ApoL9 has an
      intracytoplasmic localization and does not seem to be secreted. The cytoplasmic
      localization of ApoL9 is in line with the observation that ApoL9 inhibits the
      replication step of TMEV infection. In contrast to human ApoL6, ApoL9 did not
      sensitize cells to apoptosis, in spite of the presence of a conserved putative
      BH3 domain, required for antiviral activity. ApoL9a and b isoforms interact with
      cellular prohibitin 1 (Phb1) and prohibitin 2 (Phb2) and this interaction might
      contribute to ApoL9 antiviral activity. Knocking down Phb2 slightly increased
      TMEV replication, irrespective of ApoL9 overexpression. The antiviral activity of
      prohibitins against TMEV contrasts with the pro-viral activity of prohibitins
      observed for VSV and reported previously for Dengue 2 (DENV-2), Chikungunya
      (CHIKV) and influenza H5N1 viruses. ApoL9 is thus an example of ISG displaying a
      narrow antiviral range, which likely acts in complex with prohibitins to restrict
      TMEV replication.

PMID- 26196673
TI  - Modular, Metal-Catalyzed Cycloisomerization Approach to Angularly Fused
      Polycyclic Aromatic Hydrocarbons and Their Oxidized Derivatives.
AB  - Palladium-catalyzed cross-coupling reactions of 2-bromobenzaldehyde and 6-bromo
      2,3-dimethoxybenzaldehyde with 4-methyl-1-naphthaleneboronic acid and
      acenaphthene-5-boronic acid gave corresponding o-naphthyl benzaldehydes. Corey
      Fuchs olefination followed by reaction with n-BuLi led to various 1-(2
      ethynylphenyl)naphthalenes. Cycloisomerization of individual 1-(2
      ethynylphenyl)naphthalenes to various benzo[c]phenanthrene (BcPh) analogues was
      accomplished smoothly with catalytic PtCl2 in PhMe. In the case of 4,5
      dihydrobenzo[l]acephenanthrylene, oxidation with DDQ gave
      benzo[l]acephenanthrylene. The dimethoxy-substituted benzo[c]phenanthrenes were
      demethylated with BBr3 and oxidized to the o-quinones with PDC. Reduction of
      these quinones with NaBH4 in THF/EtOH in an oxygen atmosphere gave the respective
      dihydrodiols. Exposure of the dihydrodiols to N-bromoacetamide in THF-H2O led to
      bromohydrins that were cyclized with Amberlite IRA 400 HO(-) to yield the series
      1 diol epoxides. Epoxidation of the dihydrodiols with mCPBA gave the isomeric
      series 2 diol epoxides. All of the hydrocarbons as well as the methoxy
      substituted ones were crystallized and analyzed by X-ray crystallography, and
      these data are compared to other previously studied BcPh derivatives. The
      methodology described is highly modular and can be utilized for the synthesis of
      a wide variety of angularly fused polycyclic aromatic hydrocarbons and their
      putative metabolites and/or other derivatives. 

PMID- 26196676
TI  - Epigenetic Control of Macrophage Shape Transition towards an Atypical Elongated
      Phenotype by Histone Deacetylase Activity.
AB  - Inflammatory chronic pathologies are complex processes characterized by an
      imbalance between the resolution of the inflammatory phase and the establishment
      of tissue repair. The main players in these inflammatory pathologies are bone
      marrow derived monocytes (BMDMs). However, how monocyte differentiation is
      modulated to give rise to specific macrophage subpopulations (M1 or M2) that may
      either maintain the chronic inflammatory process or lead to wound healing is
      still unclear. Considering that inhibitors of Histone Deacetylase (HDAC) have an
      anti-inflammatory activity, we asked whether this enzyme would play a role on
      monocyte differentiation into M1 or M2 phenotype and in the cell shape transition
      that follows. We then induced murine bone marrow progenitors into
      monocyte/macrophage differentiation pathway using media containing GM-CSF and the
      HDAC blocker, Trichostatin A (TSA). We found that the pharmacological inhibition
      of HDAC activity led to a shape transition from the typical macrophage pancake
      like shape into an elongated morphology, which was correlated to a mixed M1/M2
      profile of cytokine and chemokine secretion. Our results present, for the first
      time, that HDAC activity acts as a regulator of macrophage differentiation in the
      absence of lymphocyte stimuli. We propose that HDAC activity down regulates
      macrophage plasticity favoring the pro-inflammatory phenotype.

PMID- 26196678
TI  - Generation of alpha-Imino Gold Carbenes through Gold-Catalyzed Intermolecular
      Reaction of Azides with Ynamides.
AB  - The generation of alpha-imino gold carbenes via gold-catalyzed intermolecular
      reaction of azides and ynamides is disclosed. This new methodology allows for
      highly regioselective access to valuable 2-aminoindoles and 3-amino-beta
      carbolines in generally good to excellent yields. A mechanistic rationale for
      this tandem reaction, especially for the observed high regioselectivity, is
      supported by DFT calculations. 

PMID- 26196677
TI  - Whole Exome Sequencing Identified MCM2 as a Novel Causative Gene for Autosomal
      Dominant Nonsyndromic Deafness in a Chinese Family.
AB  - We report the genetic analysis of autosomal dominant, nonsyndromic, progressive
      sensorineural hearing loss in a Chinese family. Using whole exome sequencing, we
      identified a missense variant (c.130C>T, p.R44C) in the MCM2 gene, which has a
      pro-apoptosis effect and is involved in the initiation of eukaryotic genome
      replication. This missense variant is very likely to be the disease causing
      variant. It segregated with hearing loss in this pedigree, and was not found in
      the dbSNP database or databases of genomes and SNP in the Chinese population, in
      76 patients with sporadic hearing loss, or in 145 normal individuals. We
      performed western blot and immunofluorescence to test the MCM2 protein expression
      in the cochlea of rats and guinea pigs, demonstrating that MCM2 was widely
      expressed in the cochlea and was also surprisingly expressed in the cytoplasm of
      terminally differentiated hair cells. We then transiently expressed the variant
      MCM2 cDNA in HEK293 cells, and found that these cells displayed a slight increase
      in apoptosis without any changes in proliferation or cell cycle, supporting the
      view that this variant is pathogenic. In summary, we have identified MCM2 as a
      novel gene responsible for nonsyndromic hearing loss of autosomal dominant
      inheritance in a Chinese family. 

PMID- 26196679
TI  - Mangiferin Mitigates Gastric Ulcer in Ischemia/ Reperfused Rats: Involvement of
      PPAR-gamma, NF-kappaB and Nrf2/HO-1 Signaling Pathways.
AB  - Mangiferin (MF), a xanthonoid from Mangifera indica, has been proved to have
      antisecretory and antioxidant gastroprotective effects against different gastric
      ulcer models; however, its molecular mechanism has not been previously
      elucidated. Therefore, the aim of this study was to test its modulatory effect on
      several signaling pathways using the ischemia/reperfusion model for the first
      time. Animals were treated with MF, omeprazole (OMP), and the vehicle. The
      mechanistic studies revealed that MF mediated its gastroprotective effect partly
      via inducing the expression of Nrf2, HO-1 and PPAR-gamma along with
      downregulating that of NF-kappaB. Surprisingly, the effect of MF, especially the
      high dose, exceeded that mediated by OMP except for Nrf2. The molecular results
      were reflected on the biomarkers measured, where the antioxidant effect of MF was
      manifested by increasing total antioxidant capacity and glutathione, besides
      normalizing malondialdehyde level. Additionally, MF decreased the I/R-induced
      nitric oxide elevation, an effect that was better than that of OMP. In the serum,
      MF, dose dependently, enhanced endothelial nitric oxide synthase, while reduced
      the inducible isoform. Regarding the anti-inflammatory effect of MF, it reduced
      serum level of IL-1beta and sE-selectin, effects that were mirrored on the tissue
      level of myeloperoxidase, the neutrophil infiltration marker. In addition, MF
      possessed an antiapoptotic character evidenced by elevating Bcl-2 level and
      reducing that of caspase-3 in a dose related order. As a conclusion, the
      intimated gastroprotective mechanisms of MF are mediated, partially, by
      modulation of oxidative stress, inflammation and apoptosis possibly via the
      Nrf2/HO-1, PPAR-gamma/NF-kappaB signaling pathways.

PMID- 26196680
TI  - SW480 colorectal cancer cells that naturally express Lgr5 are more sensitive to
      the most common chemotherapeutic agents than Lgr5-negative SW480 cells.
AB  - Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is a
      colorectal cancer (CRC) stem cell marker. The role of Lgr5-expressing stem cells
      in resistance to chemotherapy is controversial. The notion that Lgr5-expressing
      cells are more chemotherapy resistant is supported by some data; other data do
      not support this notion. We hypothesized that Lgr5-expressing cells would be more
      chemotherapy sensitive, as Lgr5 is usually a marker of dividing cells. We tested
      this hypothesis by exploiting two natural variants of SW480 CRC cells: the less
      differentiated Lgr5-expressing floating fraction and the more-differentiated Lgr5
      depleted attached fraction. We estimated chemotherapy sensitivity using an XTT
      Cell Proliferation Assay Kit. We confirmed that the detected chemotherapy
      sensitivity differences were Lgr5-driven by overexpressing Lgr5. SW480 CRC cells
      that naturally express Lgr5 are those that are floating, and they are more
      sensitive to the chemotherapeutic compounds irinotecan (maximum difference
      approximately two times, 0.0001<P<0.0052) and oxaliplatin (maximum difference
      ~1.5 times, 0.0001<P<0.0024) than Lgr5-negative (attached) SW480 cells. At IC50,
      the difference in sensitivity between these two fractions of SW480 cells to the
      drugs was twice as prominent with irinotecan as with oxaliplatin (P<0.0001).
      SW480 cells that naturally express Lgr5 were slightly more sensitive to 5
      fluorouracil than non-Lgr5-expressing cells (0.0002<P<0.0344). Transfected Lgr5
      overexpressing attached cells showed similar results with irinotecan and
      oxaliplatin, confirming that the detected differences in sensitivity to these
      drugs were Lgr5 driven. Most likely, Lgr5 makes cells vulnerable to chemotherapy,
      increasing their propensity to divide through activation of the Wnt/beta-catenin
      pathway. There is one exception, Lgr5-overexpressing cells did not show this
      increase in sensitivity to 5-fluorouracil. Remarkably, Lgr5 reduced the number of
      floating cells two-fold (instead of increasing it, as one would expect from a
      stemness-determining factor) and slightly increased the number of attached
      differentiated cells at a significantly high transfection efficiency for these
      SW480 cells (~30%). These results suggest that Lgr5, although purported to be a
      cancer stem cell marker, is not sufficient to promote floating in these colon
      cancer cells. In conclusion, CRC cells that naturally express Lgr5 are more
      sensitive to the most commonly used CRC chemotherapeutic compounds than those
      that are naturally Lgr5 negative. 

PMID- 26196681
TI  - Four Hybrid Materials Based on Preyssler P5W30 Polyoxometalate and First-Row
      Transition-Metal Complex.
AB  - Four Preyssler P5W30 based inorganic-organic hybrids, formulated as
      {[Cu12(pbtz)2(Hpbtz)2(OH)4(H2O)16][Na(H2O)P5W30O110]}.16H2O (1; H2pbtz = 5'
      (pyridin-2-yl)-1H,2'H-3,3'-bi(1,2,4-triazole)),
      {[Cu10(ttbz)2(Httbz)4(OH)6(H2O)8][K(H2O)H2P5W30O110]}.30H2O (2; Httbz = 1
      (tetrazo-5-yl)-4-(triazo-1-yl)benzene),
      {[Ni6(bpz)6(H2O)16][Na(H2O)H2P5W30O110]}.36H2O (3; bpz = 3,3',5,5'-tetramethyl
      4,4-bipyrazole), {[Co4(bpz)6(H2O)9][K(H2O)H6P5W30O110]}.46H2O (4), have been
      isolated and structurally identified via microanalysis, thermogravimetry (TG),
      infrared (IR) spectroscopy, and X-ray single-crystal diffraction. Compound 1
      exhibits a 3D binodal (3,6)-connected ant framework composed of dodeca-supported
      P5W30 polyoxometalate (POM) clusters and discrete [Cu6(pbtz)(Hpbtz)(OH)2(H2O)8]
      subunits. Compound 2 is a pillared-layer 3D network constructed from
      [Cu5(ttbz)(Httbz)2(OH)3(H2O)4] sheets pillared by individual P5W30 clusters.
      Compound 3 contains octa-supporting P5W30 POM clusters and novel [Ni6(bpz)6]
      crown-like metallamacrocycles, which construct a (4,4)-connected pts network.
      Compound 4 displays a complicated 3D (5,5)-connected {4(5).6(4).8}{4(5).6(5)}
      network built by pentasupporting P5W30 POM clusters and discrete
      [Co4(bpz)6(H2O)9] subunits. In 1-4, the unified features are the Preyssler-type
      [P5W30O110] POM as the fundamental building block, which supports the transition
      metal compounds with different modes to give the resultant diverse networks. The
      magnetism studies indicated antiferromagnetically coupled systems for the hexa-
      and pentanuclear Cu(II) units in 1 and 2, respectively. The electrochemical
      properties demonstrate that all compounds have electrocatalytic abilities toward
      the reduction of hydrogen peroxide. Furthermore, the catalytic activities of 1 in
      the cyanosilylation of aldehydes reaction have been investigated. 

PMID- 26196682
TI  - Transcriptome Analysis of Beta macrocarpa and Identification of Differentially
      Expressed Transcripts in Response to Beet Necrotic Yellow Vein Virus Infection.
AB  - BACKGROUND: Rhizomania is one of the most devastating diseases of sugar beet. It
      is caused by Beet necrotic yellow vein virus (BNYVV) transmitted by the obligate
      root-infecting parasite Polymyxa betae. Beta macrocarpa, a wild beet species
      widely used as a systemic host in the laboratory, can be rub-inoculated with
      BNYVV to avoid variation associated with the presence of the vector P. betae. To
      better understand disease and resistance between beets and BNYVV, we
      characterized the transcriptome of B. macrocarpa and analyzed global gene
      expression of B. macrocarpa in response to BNYVV infection using the Illumina
      sequencing platform. RESULTS: The overall de novo assembly of cDNA sequence data
      generated 75,917 unigenes, with an average length of 1054 bp. Based on a BLASTX
      search (E-value <= 10-5) against the non-redundant (NR, NCBI) protein, Swiss
      Prot, the Gene Ontology (GO), Clusters of Orthologous Groups of proteins (COG)
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, there were 39,372
      unigenes annotated. In addition, 4,834 simple sequence repeats (SSRs) were also
      predicted, which could serve as a foundation for various applications in beet
      breeding. Furthermore, comparative analysis of the two transcriptomes revealed
      that 261 genes were differentially expressed in infected compared to control
      plants, including 128 up- and 133 down-regulated genes. GO analysis showed that
      the changes in the differently expressed genes were mainly enrichment in response
      to biotic stimulus and primary metabolic process. CONCLUSION: Our results not
      only provide a rich genomic resource for beets, but also benefit research into
      the molecular mechanisms of beet- BNYV Vinteraction.

PMID- 26196684
TI  - Is the Risk Difference Really a More Heterogeneous Measure?
AB  - There are claims in the literature that the risk difference is a more
      heterogeneous measure than the odds ratio or risk ratio. These claims are based
      on surveys of meta-analyses showing that tests reject the null hypothesis of
      homogeneity more often for the risk difference than for the ratio measures.
      Discussions of this point have neglected the fact that homogeneity tests can have
      different levels of statistical power (i.e., different probabilities of rejecting
      the null when it is false) across different scales. We give hypothetical examples
      in which there is arguably equal heterogeneity across risk difference and odds
      ratio measures but in which the risk difference homogeneity test rejects more
      often, and therefore has higher power, than the odds ratio homogeneity test.
      These examples suggest that current empirical evidence for the claim that the
      risk difference is more heterogeneous is not at present satisfactory. Further
      research could consider other approaches to empirical comparisons of the
      heterogeneity of the three measures. 

PMID- 26196683
TI  - Comparative Effectiveness of Oxaliplatin Versus 5-flourouricil in Older Adults:
      An Instrumental Variable Analysis.
AB  - BACKGROUND: Oxaliplatin was rapidly adopted for treatment of stage III colon
      cancer after FDA approval in November 2004, thus providing an opportunity to use
      calendar time as an instrumental variable in nonexperimental comparative
      effectiveness research. Assuming instrument validity, instrumental variable
      analyses account for unmeasured confounding and are particularly valuable in sub
      populations of unresolved effectiveness, such as older individuals. METHODS: We
      examined stage III colon cancer patients ages 65+ years initiating chemotherapy
      between 2003 and 2008 using US population-based cancer registry data linked with
      Medicare claims (N = 3,660). Risk differences for all-cause mortality were
      derived from Kaplan-Meier survival curves. We examined instrumental variable
      strength and compared risk differences with propensity score estimates. RESULTS:
      Calendar time greatly affected oxaliplatin receipt. The calendar time instrument
      compared patients treated from January 2003 through September 2004 (N = 1,449)
      with those treated from March 2005 through May 2007 (N = 1,432), resulting in 54%
      compliance. The 1-, 2-, and 3-year local average treatment effect of the risk
      differences per 100 patients in the "compliers" (95% confidence intervals) were 
      4.6 (-8.2, -0.44), -6.3 (-12, -0.16), and -9.2 (-15, -2.5), respectively.
      Corresponding propensity score-matched results were -1.9 (-4.0, 0.2), -3.4 (-6.2,
      -0.05), and -4.3 (-7.5, -0.96). CONCLUSIONS: Instrumental variable and propensity
      score analyses both indicate better survival among patients treated with
      oxaliplatin. As these results are based on different populations and assumptions,
      the instrumental variable analysis adds to evidence of oxaliplatin's
      effectiveness in older adults, who bear the greatest burden of colon cancer yet
      were underrepresented in clinical trials. In nonexperimental comparative
      effectiveness research of rapidly emerging therapies, the potential to use
      calendar time as an instrumental variable is worth consideration.

PMID- 26196685
TI  - Commentary: On Effect Measures, Heterogeneity, and the Laws of Nature.

PMID- 26196686
TI  - Spatial Distribution of Dengue in a Brazilian Urban Slum Setting: Role of
      Socioeconomic Gradient in Disease Risk.
AB  - BACKGROUND: Few studies of dengue have shown group-level associations between
      demographic, socioeconomic, or geographic characteristics and the spatial
      distribution of dengue within small urban areas. This study aimed to examine
      whether specific characteristics of an urban slum community were associated with
      the risk of dengue disease. METHODOLOGY/PRINCIPAL FINDINGS: From 01/2009 to
      12/2010, we conducted enhanced, community-based surveillance in the only public
      emergency unit in a slum in Salvador, Brazil to identify acute febrile illness
      (AFI) patients with laboratory evidence of dengue infection. Patient households
      were geocoded within census tracts (CTs). Demographic, socioeconomic, and
      geographical data were obtained from the 2010 national census. Associations
      between CTs characteristics and the spatial risk of both dengue and non-dengue
      AFI were assessed by Poisson log-normal and conditional auto-regressive models
      (CAR). We identified 651 (22.0%) dengue cases among 2,962 AFI patients. Estimated
      risk of symptomatic dengue was 21.3 and 70.2 cases per 10,000 inhabitants in 2009
      and 2010, respectively. All the four dengue serotypes were identified, but DENV2
      predominated (DENV1: 8.1%; DENV2: 90.7%; DENV3: 0.4%; DENV4: 0.8%). Multivariable
      CAR regression analysis showed increased dengue risk in CTs with poorer
      inhabitants (RR: 1.02 for each percent increase in the frequency of families
      earning <=1 times the minimum wage; 95% CI: 1.01-1.04), and decreased risk in CTs
      located farther from the health unit (RR: 0.87 for each 100 meter increase; 95%
      CI: 0.80-0.94). The same CTs characteristics were also associated with non-dengue
      AFI risk. CONCLUSIONS/SIGNIFICANCE: This study highlights the large burden of
      symptomatic dengue on individuals living in urban slums in Brazil. Lower
      neighborhood socioeconomic status was independently associated with increased
      risk of dengue, indicating that within slum communities with high levels of
      absolute poverty, factors associated with the social gradient influence dengue
      transmission. In addition, poor geographic access to health services may be a
      barrier to identifying both dengue and non-dengue AFI cases. Therefore, further
      spatial studies should account for this potential source of bias.

PMID- 26196687
TI  - Association between Sick Leave Prescribing Practices and Physician Burnout and
      Empathy.
AB  - OBJECTIVES: To investigate the association between sick leave prescription and
      physician burnout and empathy in a primary care health district in Lleida, Spain.
      METHODS: This descriptive study included 108 primary care doctors from 22 primary
      care centers in Lleida in 2014 (183,600 patients). Burnout was measured with the
      Maslach Burnout Inventory and empathy with the Jefferson Scale of Physician
      Empathy. The reliability of the instruments was measured by calculating
      Cronbach's alpha and normal distribution was analyzed using the Kolmogorov
      Smirnov-Lilliefors and chi2 tests. Burnout and empathy scores were analyzed by
      age, sex, and place of work (urban vs rural). Sick leave data were obtained from
      the Catalan Health Institute. RESULTS: High empathy was significantly associated
      with low burnout. Neither empathy nor burnout were significantly associated with
      sick leave prescription. CONCLUSION: Sick leave prescription by physicians is not
      associated with physicians' empathy or burnout and may mostly depend on
      prescribing guidelines.

PMID- 26196688
TI  - Factors Associated with the Development of Drug Resistance Mutations in HIV-1
      Infected Children Failing Protease Inhibitor-Based Antiretroviral Therapy in
      South Africa.
AB  - OBJECTIVE: Limited data are available from the developing world on antiretroviral
      drug resistance in HIV-1 infected children failing protease inhibitor-based
      antiretroviral therapy, especially in the context of a high tuberculosis burden.
      We describe the proportion of children with drug resistance mutations after
      failed protease inhibitor-based antiretroviral therapy as well as associated
      factors. METHODS: Data from children initiated on protease inhibitor-based
      antiretroviral therapy with subsequent virological failure referred for genotypic
      drug resistance testing between 2008 and 2012 were retrospectively analysed.
      Frequencies of drug resistance mutations were determined and associations with
      these mutations identified through logistic regression analysis. RESULTS: The
      study included 65 young children (median age 16.8 months [IQR 7.8; 23.3]) with
      mostly advanced clinical disease (88.5% WHO stage 3 or 4 disease), severe
      malnutrition (median weight-for-age Z-score -2.4 [IQR -3.7;-1.5]; median height
      for-age Z-score -3.1 [IQR -4.3;-2.4]), high baseline HIV viral load (median 6.04
      log10, IQR 5.34;6.47) and frequent tuberculosis co-infection (66%) at
      antiretroviral therapy initiation. Major protease inhibitor mutations were found
      in 49% of children and associated with low weight-for-age and height-for-age (p =
      0.039; p = 0.05); longer duration of protease inhibitor regimens and virological
      failure (p = 0.001; p = 0.005); unsuppressed HIV viral load at 12 months of
      antiretroviral therapy (p = 0.001); tuberculosis treatment at antiretroviral
      therapy initiation (p = 0.048) and use of ritonavir as single protease inhibitor
      (p = 0.038). On multivariate analysis, cumulative months on protease inhibitor
      regimens and use of ritonavir as single protease inhibitor remained significant
      (p = 0.008; p = 0.033). CONCLUSION: Major protease inhibitor resistance mutations
      were common in this study of HIV-1-infected children, with the timing of
      tuberculosis treatment and subsequent protease inhibitor dosing strategy proving
      to be important associated factors. There is an urgent need for safe, effective,
      and practicable HIV/tuberculosis co-treatment in young children and the optimal
      timing of treatment, optimal dosing of antiretroviral therapy, and alternative
      tuberculosis treatment strategies should be urgently addressed.

PMID- 26196689
TI  - Perioperative Outcomes in Patients Requiring Iliac Conduits or Direct Access for
      Endovascular Abdominal Aortic Aneurysm Repair.
AB  - BACKGROUND: Iliac conduit or direct iliac access (ICDA) can be used when anatomy
      is unfavorable for femoral access during abdominal endovascular aortic aneurysm
      repair (EVAR). The impact of this approach has not been adequately addressed. The
      objective of this study was to analyze perioperative outcomes of patients
      requiring use of ICDAs for EVAR. METHODS: Patients undergoing EVAR with and
      without ICDA were identified in the 2005-2012 National Surgical Quality
      Improvement Program data sets. Perioperative morbidity and mortality were
      assessed by crude comparison of matched groups and multivariate analyses.
      RESULTS: Of 15,082 patients undergoing infrarenal EVAR 147 (1%) required ICDA.
      The ICDA group had a higher proportion of females (25.9% vs. 17.8%, P = 0.017),
      peripheral vascular disease (12.9% vs. 5.5%, P = 0.001), and patients with a
      history of dyspnea (31.3% vs. 23.1%, P = 0.024). There was no difference in age
      (74.5 +/- 8.4 conduit vs. 73.5 +/- 8.5). On multivariate analysis, the ICDA
      cohort had a higher rate of mortality (odds ratio [OR], 2.7; 95% confidence
      interval [CI], 1.4-5.4; P = 0.004) and an increase in other major complications
      including cardiac arrest and/or myocardial infarction (OR, 2.9; 95% CI, 1.3-6.3;
      P = 0.007), pulmonary complications (OR, 2.1; 95% CI, 1.2-3.9; P = 0.013), and
      postoperative length of stay (means ratio, 1.3; 95% CI, 1.1-1.4; P = 0.001).
      There was a trend toward increased bleeding complications with ICDA. Matched
      analyses of comorbidities revealed that patients requiring ICDA had higher
      perioperative mortality (6.8% vs. 2.3%, P = 0.008), cardiac (4.8% vs. 1%, P =
      0.004), pulmonary (8.8% vs. 3.4%, P = 0.006), and bleeding complications (10.2%
      vs. 4.6%, P = 0.016). CONCLUSIONS: Our results demonstrate that the use of ICDA
      during EVAR is associated with increased morbidity and mortality. In situations
      where anatomy mandates the use of iliac conduits or access for EVAR, surgeons
      should consider this increased risk. Open repair or the use of lower profile
      devices, if possible, should be considered as options for these patients.

PMID- 26196690
TI  - The Trametes hirsuta 072 laccase multigene family: Genes identification and
      transcriptional analysis under copper ions induction.
AB  - Laccases, blue copper-containing oxidases, ? an play an important role in a
      variety of natural processes. The majority of fungal laccases are encoded by
      multigene families that express closely related proteins with distinct functions.
      Currently, only the properties of major gene products of the fungal laccase
      families have been described. Our study is focused on identification and
      characterization of laccase genes, which are transcribed in basidiomycete
      Trametes hirsuta 072, an efficient lignin degrader, in a liquid medium, both
      without and with induction of laccase transcription by copper ions. We carried
      out production of cDNA libraries from total fungal RNA, followed by suppression
      subtractive hybridization and mirror orientation selection procedures, and then
      used Next Generation Sequencing to identify low abundance and differentially
      expressed laccase transcripts. This approach resulted in description of five
      laccase genes of the fungal family, which, according to the phylogenetic
      analysis, belong to distinct clusters within the Trametes genus. Further analysis
      established similarity of physical, chemical, and catalytic properties between
      laccases inside each cluster. Structural modeling suggested importance of the
      sequence differences in the clusters for laccase substrate specificity and
      catalytic efficiency. The implications of the laccase variations for the fungal
      physiology are discussed.

PMID- 26196691
TI  - A novel antifungal peptide from leaves of the weed Stellaria media L.
AB  - A novel peptide named SmAMP3 was isolated from leaves of common chickweed
      (Stellaria media L.) by a combination of acidic extraction and a single-step
      reversed-phase HPLC and sequenced. The peptide is basic and cysteine-rich,
      consists of 35 amino acids, and contains three disulphide bridges. Homology
      search revealed that SmAMP3 belongs to the family of hevein-like antimicrobial
      peptides carrying a conserved chitin-binding site. Efficient binding of chitin by
      SmAMP3 was proved by in vitro assays. Molecular modeling confirmed conservation
      of the chitin-binding module in SmAMP3 locating the variable amino acid residues
      to the solvent-exposed loops of the molecule. The peptide exhibits potent
      antifungal activity against important plant pathogens in the micromolar range,
      although it is devoid of antibacterial activity at concentrations below 10 MUM.
      As judged by chromatographic behavior and mass spectrometric data, the peptide is
      constitutively expressed in above-ground organs and seeds of S. media plants,
      thus representing an important player in the preformed branch of the plant immune
      system.

PMID- 26196692
TI  - Fever Is Mediated by Conversion of Endocannabinoid 2-Arachidonoylglycerol to
      Prostaglandin E2.
AB  - Fever is a common response to inflammation and infection. The mechanism involves
      prostaglandin E2 (PGE2)-EP3 receptor signaling in the hypothalamus, which raises
      the set point of hypothalamic thermostat for body temperature, but the lipid
      metabolic pathway for pyretic PGE2 production remains unknown. To reveal the
      molecular basis of fever initiation, we examined lipopolysaccharides (LPS)
      induced fever model in monoacylglycerol lipase (MGL)-deficient (Mgll-/-) mice,
      CB1 receptor-MGL compound-deficient (Cnr1-/-Mgll-/-) mice, cytosolic
      phospholipase A2alpha (cPLA2alpha)-deficient (Pla2g4a-/-) mice, and
      diacylglycerol lipase alpha (DGLalpha)-deficient (Dagla-/-) mice. Febrile
      reactions were abolished in Mgll-/- and Cnr1-/-Mgll-/- mice, whereas Cnr1-/
      Mgll+/+, Pla2g4a-/- and Dagla-/- mice responded normally, demonstrating that MGL
      is a critical enzyme for fever, which functions independently of endocannabinoid
      signals. Intracerebroventricular administration of PGE2 caused fever similarly in
      Mgll-/- and wild-type control mice, suggesting a lack of pyretic PGE2 production
      in Mgll-/- hypothalamus, which was confirmed by lipidomics analysis. Normal blood
      cytokine responses after LPS administration suggested that MGL-deficiency does
      not affect pyretic cytokine productions. Diurnal body temperature profiles were
      normal in Mgll-/- mice, demonstrating that MGL is unrelated to physiological
      thermoregulation. In conclusion, MGL-dependent hydrolysis of endocannabinoid 2
      arachidonoylglycerol is necessary for pyretic PGE2 production in the
      hypothalamus. 

PMID- 26196693
TI  - Association between the Interaction of Key Genes Involved in Effector T-Cell
      Pathways and Susceptibility to Develop allergic Rhinitis: A Population-Based Case
      Control Association Study.
AB  - BACKGROUND: Evidence suggests that interaction between key genes mediating
      signaling and transcriptional networks involving effector T-cell responses may
      influence an individual's susceptibility to develop allergic rhinitis(AR).
      OBJECTIVE: The aim of this study was todetermine whether specific interactions
      between key genes involved in effector T-cell pathways are associated with an
      individual's susceptibility to develop AR in Han Chinese subjects. METHOD: A
      cohort of 489 patients with AR and 421 healthy controls was enrolled from the Han
      Chinese population in Beijing, China. AR was established by questionnaire and
      clinical examination, and peripheral blood was drawn from all subjects for DNA
      extraction. A total of 96 single nucleotide polymorphisms (SNPs) in 26
      reprehensive candidate genes involved in T helper 1 (Th1), Th2, Th17, Th9 and T
      regulatory cell pathways were selected from the International Haplotype
      Mappingdatabase for Han Chinese in Beijing (CHB) population, and
      IlluminaGoldenGate assay was conducted for SNP genotyping. The PLINK software
      package was used to perform statistical analyses. RESULTS: Simple SNP-phenotype
      association analysis using logistic regression showed SNP rs8193036 in IL17A
      gene, rs2569254 in IL-12 and rs1898413 in RORalpha
      weresignificantlyassociatedwith AR.Simple SNP-phenotype association analysis with
      genetic models demonstrated thatrs2569254 in IL-12, rs1031508 in STAT4, and
      rs3741809 in IL-26 were likely to be recessive, rs8193036 in IL17A allelic,
      rs897200in STAT4 genotypic, and rs1898413 in RORalpha dominant. Epistasis
      analyses exhibited that 83 SNPs in 23 genes were significantly interactive; of
      which 59 interactions/SNP pairs demonstrated OR values higher than 2 or lower
      than 0.5, and 12 interactions/SNP pairs OR values higher than 4 or lower than
      0.25. STAT3, RORalpha and IL-26, involved in Th17 pathway,were the
      mostfrequentlyinteractive genes. CONCLUSION: This study suggests that
      interactions between several SNPs in key genes involved in effector T-cell
      pathways are likely to influence an individual's susceptibility to develop AR.

PMID- 26196695
TI  - Predictors of Clinical Success in the Treatment of Patients with Methicillin
      Resistant Staphylococcus aureus (MRSA) Nosocomial Pneumonia (NP).
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) remains an important pathogen
      in nosocomial pneumonia and is associated with significant morbidity and
      mortality. Clinical outcomes for nosocomial pneumonia are dependent on patient
      age, co-morbidities, severity of illness and appropriate antibiotic therapy. The
      objective of this secondary analysis was to identify baseline clinical variables
      that are associated with clinical success at the end of the study observation
      period. Data from a randomized blinded trial (NCT00084266) comparing linezolid
      (600-mg twice daily) to vancomycin (15-mg/kg twice daily, dose-adjusted) for the
      treatment of culture-proven MRSA pneumonia were analyzed to evaluate baseline
      clinical and demographic factors that may predict clinical success at end of
      study (EOS) (7-30 days after end of treatment). A multivariate logistic
      regression was conducted to identify baseline factors that are associated with
      clinical success. Patients treated with linezolid (OR 1.55 95% CI: 1.013, 2.355),
      no vasopressor receipt (OR 2.30, 95% CI: 1.303, 4.069), unilateral involvement
      (OR 1.70, 95% CI: 1.078, 2.681) and normal renal function (eGFR 30-80 vs >80 OR
      0.48, 95% CI: 0.303, 0.750) were more likely to have clinical success. From a
      clinical standpoint, identifying reliable predictors of outcome and who might
      benefit more from one therapy versus another can help inform treatment decisions.

PMID- 26196696
TI  - Correction: Suppression of MAPK Signaling and Reversal of mTOR-Dependent MDR1
      Associated Multidrug Resistance by 21alpha-Methylmelianodiol in Lung Cancer
      Cells.

PMID- 26196697
TI  - Physiotherapy as a promoter of sexual health.
AB  - Despite the holistic intention of physiotherapy, sexual health receives
      insufficient attention by physiotherapists. Sexual health is an important part of
      general health and well-being, which is often negatively affected by physical and
      psychological disorders. There are several reasons why sexual health should be
      addressed by physiotherapists, and this article aims to describe the role of the
      physiotherapist as a promoter of good sexual health and implementation of sexual
      health in clinical physiotherapy. 

PMID- 26196694
TI  - miR-150 Deficiency Protects against FAS-Induced Acute Liver Injury in Mice
      through Regulation of AKT.
AB  - Although miR-150 is implicated in the regulation of immune cell differentiation
      and activation, it remains unknown whether miR-150 is involved in liver biology
      and disease. This study was performed to explore the potential role of miR-150 in
      LPS/D-GalN and Fas-induced liver injuries by using wild type and miR-150 knockout
      (KO) mice. Whereas knockout of miR-150 did not significantly alter LPS/D-GalN
      induced animal death and liver injury, it protected against Fas-induced liver
      injury and mortality. The Jo2-induced increase in serum transaminases, apoptotic
      hepatocytes, PARP cleavage, as well as caspase-3/7, caspase-8, and caspase-9
      activities were significantly attenuated in miR-150 KO mice. The liver tissues
      from Jo2-treated miR-150 KO mice expressed higher levels of Akt1, Akt2, total
      Akt, as well as p-Akt(Ser473) compared to the wild type livers. Pretreatment with
      the Akt inhibitor V reversed Jo2-induced liver injury in miR-150 KO mice. The
      primary hepatocytes isolated from miR-150 KO mice also showed protection against
      Fas-induced apoptosis in vitro (characterized by less prominent PARP cleavage,
      less nuclear fragmentation and less caspase activation) in comparison to
      hepatocytes from wild type mice. Luciferase reporter assays in hepatocytes
      transfected with the Akt1 or Akt2 3'-UTR reporter constructs (with or without
      mutation of miR-150 binding site) established Akt1 and Akt2 as direct targets of
      miR-150. Tail vein injection of lentiviral particles containing pre-miR-150
      enhanced Jo2-induced liver injury in miR-150 KO mice. These findings demonstrate
      that miR-150 deficiency prevents Fas-induced hepatocyte apoptosis and liver
      injury through regulation of the Akt pathway.

PMID- 26196698
TI  - Physiotherapists' stories about professional development.
AB  - INTRODUCTION: A professional career may extend over a period of 40 years.
      Although learning is a feature of professional competence, little is known about
      learning and development after professional entry education. METHODS: Narrative
      inquiry was used to understand how physiotherapists learned and developed over
      time, and stories from a purposeful sample of 12 physiotherapists were collected.
      Stories were thematically analyzed with regard to key elements related to
      learning and development, and common themes were identified across stories.
      FINDINGS: Four themes emerged from the analysis where physiotherapists learned
      and developed in working life: (1) facing challenges; (2) contrasting
      perspectives; (3) drawing on hundreds of educators; and (4) building on personal
      experience. CONCLUSION: Non-formal ways of learning in working life may help
      physiotherapists learn and develop confidence, communication strategies and
      different approaches to treatment. Besides reflection on personal experience and
      patient encounters, learning and development may be promoted and supported by
      taking on challenges and changing settings.

PMID- 26196700
TI  - Rehabilitation considerations for a patient with external hemipelvectomy and
      hemisacrectomy for recurrent soft tissue pelvic sarcoma: a case report.
AB  - BACKGROUND AND PURPOSE: External hemipelvectomy (EHP) is an uncommon procedure
      involving surgical amputation of the lower extremity and hemipelvis. Soft tissue
      sarcomas of the pelvis are rare and accompanied by a high risk of disease
      progression after surgical intervention. The purpose of this case report is to
      describe the rehabilitation considerations and importance of interdisciplinary
      collaboration to achieve functional goals to allow discharge with improved
      independence and decreased caregiver burden. CASE DESCRIPTION: A 58-year-old
      Caucasian male patient underwent a hemipelvectomy and hemisacrectomy for
      treatment of a recurrent pelvic soft tissue sarcoma following 4 months of bed
      confinement secondary to pain and weakness of the involved lower extremity. This
      report outlines the physical therapy interventions during 3 weeks of inpatient
      rehabilitation. CONCLUSION: This case demonstrates that continuous
      interdisciplinary care of a complex patient with EHP and hemisacrectomy
      contributes to significant improvement in functional mobility exceeding prior
      level of function. This case is particularly interesting because in addition to
      having a rare diagnosis and undergoing an uncommon surgical procedure, this
      patient was confined to bed for 4 months prior to surgical intervention, and thus
      began rehabilitation with a baseline of limited functional mobility and high
      caregiver burden.

PMID- 26196699
TI  - Sincerity of effort versus feigned movement control of the cervical spine in
      patients with whiplash-associated disorders and asymptomatic persons: a case
      control study.
AB  - STUDY DESIGN: Cross-sectional design. OBJECTIVES: To investigate whether the Fly
      Test can be used to differentiate patients with whiplash-associated disorders
      (WAD) from asymptomatic persons who deliberately feign symptoms and from WAD
      patients exaggerating symptoms. BACKGROUND: The lack of valid clinical tests
      makes it difficult to detect a justifiable cause for compensation claims in
      traumatic neck-pain disorders. METHODS: The Fly Test recorded the accuracy of
      neck movements in patients with WAD (n = 34) and asymptomatic persons (n = 31).
      The participants followed a moving "Fly" on a computer screen with a cursor from
      sensors mounted on the head. Two conditions were tested, sincere versus feigned
      efforts. In the former, the participants moved their neck as accurately as
      possible. In the latter, a short text was presented describing a fictitious
      accident (asymptomatic group) or imagining more intense pain/suffering (WAD
      group), and the test was performed as affected by these more serious conditions.
      Amplitude accuracy (AA), time on target (ToT) and jerk index (JI) were compared
      across patterns, conditions and groups. RESULTS: The sincere effort in the WAD
      group was significant compared to the feigned effort of the asymptomatic group (p
      < 0.001). For AA, correct categorization of 81.5% of the performances was made,
      where a mean score above 5.5 mm differentiated feigned versus sincere efforts in
      asymptomatic and WAD groups (sensitivity 79.4%, specificity 67.7%). For ToT,
      score above 11% indicated correctly categorized WAD patients (sensitivity 82.4%,
      specificity 64.5%). CONCLUSION: The Fly Test can provide clinicians a clue when
      patients with mild to moderate pain/disability are feigning or exaggerating
      symptoms.

PMID- 26196701
TI  - Concussion-Management Practice Patterns of National Collegiate Athletic
      Association Division II and III Athletic Trainers: How the Other Half Lives.
AB  - CONTEXT: The National Collegiate Athletic Association (NCAA) has published
      concussion-management practice guidelines consistent with recent position and
      consensus statements. Whereas NCAA Division I athletic trainers appear highly
      compliant, little is known about the concussion-management practice patterns of
      athletic trainers at smaller institutions where staffing and resources may be
      limited. OBJECTIVE: To descriptively define the concussion-management practice
      patterns of NCAA Division II and III athletic trainers. DESIGN: Cross-sectional
      study. SETTING: Web-based questionnaire. PATIENTS OR OTHER PARTICIPANTS: A total
      of 755 respondents (response rate = 40.2%) from NCAA Division II and Division III
      institutions. MAIN OUTCOME MEASURE(S): The primary outcome measures were the rate
      of multifaceted concussion-assessment techniques, defined as 3 or more
      assessments; the specific practice patterns of each assessment battery; and tests
      used during a clinical examination. RESULTS: Most respondents indicated using a
      multifaceted assessment during acute assessment (Division II = 76.9%, n = 473;
      Division III = 76.0%, n = 467) and determination of recovery (Division II =
      65.0%, n = 194; Division III = 63.1%, n = 288) but not at baseline (Division II =
      43.1%, n = 122; Division III = 41.0%, n = 176). Typically, when a postconcussion
      assessment was initiated, testing occurred daily until baseline values were
      achieved, and most respondents (80.6% [244/278]) reported using a graded exercise
      protocol before return to participation. CONCLUSIONS: We found limited use of the
      multifaceted assessment battery at baseline but higher rates at both acute
      assessment and return-to-participation time points. A primary reason cited for
      not using test-battery components was a lack of staffing or funding for the
      assessments. We observed limited use of neuropsychologists to interpret
      neuropsychological testing. Otherwise, most respondents reported concussion
      management protocols consistent with recommendations, including a high level of
      use of objective measures and incorporation of a progressive return-to
      participation protocol.

PMID- 26196702
TI  - Epidemiology of National Collegiate Athletic Association Women's Gymnastics
      Injuries, 2009-2010 Through 2013-2014.
AB  - CONTEXT: Recent injury-surveillance data for collegiate-level women's gymnastics
      are limited. In addition, researchers have not captured non-time-loss injuries
      (ie, injuries resulting in restriction of participation <1 day). OBJECTIVE: To
      describe the epidemiology of National Collegiate Athletic Association (NCAA)
      women's gymnastics injuries during the 2009-2010 through 2013-2014 academic
      years. DESIGN: Descriptive epidemiology study. SETTING: Aggregate injury and
      exposure data collected from 11 women's gymnastics programs providing 28 seasons
      of data. PATIENTS OR OTHER PARTICIPANTS: Collegiate student-athletes
      participating in women's gymnastics during the 2009-2010 through 2013-2014
      academic years. INTERVENTION(S): Women's gymnastics data from the NCAA Injury
      Surveillance Program (ISP) during the 2009-2010 through 2013-2014 academic years
      were analyzed. MAIN OUTCOME MEASURE(S): Injury rates; injury rate ratios; injury
      proportions by body site, diagnosis, and apparatus; and injury proportion ratios
      were reported with 95% confidence intervals (CIs). RESULTS: The ISP captured 418
      women's gymnastics injuries, a rate of 9.22/1000 athlete-exposures (AEs; 95% CI =
      8.33, 10.10). The competition injury rate (14.49/1000 AEs) was 1.67 times the
      practice injury rate (8.69/1000 AEs; 95% CI = 1.27, 2.19). When considering time
      loss injuries only, the injury rate during this study period (3.62/1000 AEs) was
      lower than rates reported in earlier NCAA ISP surveillance data. Commonly injured
      body sites were the ankle (17.9%, n = 75), lower leg/Achilles tendon (13.6%, n =
      57), trunk (13.4%, n = 56), and foot (12.4%, n = 52). Common diagnoses were
      ligament sprain (20.3%, n = 85) and muscle/tendon strain (18.7%, n = 78).
      Overall, 12.4% (n = 52) of injuries resulted in time loss of more than 3 weeks.
      Of the 291 injuries reported while a student-athlete used an apparatus (69.6%),
      most occurred during the floor exercise (41.9%, n = 122) and on the uneven bars
      (28.2%, n = 82). CONCLUSIONS: We observed a lower time-loss injury rate for
      women's gymnastics than shown in earlier NCAA ISP surveillance data. Safety
      initiatives in women's gymnastics, such as "sting mats," padded equipment, and a
      redesigned vault table, may have contributed to minimizing the frequency and
      severity of injury.

PMID- 26196703
TI  - Landing Error Scoring System Differences Between Single-Sport and Multi-Sport
      Female High School-Aged Athletes.
AB  - CONTEXT: Single-sport specialization (SSS) is becoming more prevalent in youth
      athletes. Deficits in functional movement have been shown to predispose athletes
      to injury. It is unclear whether a link exists between SSS and the development of
      functional movement deficits that predispose SSS athletes to an increased risk of
      knee injury. OBJECTIVE: To determine whether functional movement deficits exist
      in SSS athletes compared with multi-sport (M-S) athletes. DESIGN: Cross-sectional
      study. SETTING: Soccer practice fields. PATIENTS OR OTHER PARTICIPANTS: A total
      of 40 (21 SSS [age = 15.05 +/- 1.2 years], 19 M-S [age = 15.32 +/- 1.2 years])
      female high school athlete volunteers were recruited through local soccer clubs.
      All SSS athletes played soccer. INTERVENTION(S): Participants were grouped into 2
      categories: SSS and M-S. All participants completed 3 trials of the standard
      Landing Error Scoring System (LESS) jump-landing task. They performed a double
      legged jump from a 30-cm platform, landing on a rubber mat at a distance of half
      their body height. Upon landing, participants immediately performed a maximal
      vertical jump. MAIN OUTCOME MEASURE(S): Values were assigned to each trial using
      the LESS scoring criteria. We averaged the 3 scored trials and then used a Mann
      Whitney U test to test for differences between groups. Participant scores from
      the jump-landing assessment for each group were also placed into the 4 defined
      LESS categories for group comparison using a Pearson chi(2) test. The alpha level
      was set a priori at .05. RESULTS: Mean scores were 6.84 +/- 1.81 for the SSS
      group and 6.07 +/- 1.93 for the M-S group. We observed no differences between
      groups (z = -1.44, P = .15). A Pearson chi(2) analysis revealed that the
      proportions of athletes classified as having excellent, good, moderate, or poor
      LESS scores were not different between the SSS and M-S groups ([Formula: see
      text] = 1.999, P = .57). CONCLUSIONS: Participation in soccer alone compared with
      multiple sports did not affect LESS scores in adolescent female soccer players.
      However, the LESS scores indicated that most female adolescent athletes may be at
      an increased risk for knee injury, regardless of the number of sports played.

PMID- 26196704
TI  - Comparison of Flow Characteristics of Novel Three-Dimensional Printed Ureteral
      Stents Versus Standard Ureteral Stents in a Porcine Model.
AB  - PURPOSE: We compared the flow characteristics of novel three-dimensional (3D)
      printed ureteral stents with four conventional double-pigtail stents in an ex
      vivo porcine model. MATERIALS AND METHODS: In six ex vivo porcine urinary systems
      with kidneys and ureters intact, we deployed a 5F occlusion catheter in an
      interpolar calix. We tested each system with antegrade irrigation with a 0.9%
      saline bag placed 35 cm above the renal pelvis. We evaluated four standard stents
      (6F Universa(r) Soft, 7F Percuflex,TM 7/10F Applied Endopyelotomy, 8.5F Filiform
      Double Pigtail) and compared them with a 9F 3D printed prototype stent. For each
      stent, we measured the total, extraluminal, and intraluminal flow rates. RESULTS:
      The mean total flow rates for 3D printed stents were significantly higher than
      the 6F, 7F, and 7/10F stents (P<0.05). No significant difference was seen in the
      total flow rate for the 3D printed stent and the 8.5F stent. The mean
      extraluminal flow rates for the 3D stents were similar to those of 7F stents, but
      significantly lower than 6F stents (P<0.001) and 8.5F stents (P<0.05) and higher
      than 7/10F stents (P<0.001). The mean intraluminal flow rates for the 3D printed
      stents were significantly higher than the 6F, 7F, 7/10F, and 8.5F stents
      (P<0.05). CONCLUSIONS: In this pilot study, 3D printed stents manifested a mean
      total flow rate comparable to the flow rates of contemporary stents. Continued
      advances in technology and material may permit functionally feasible 3D printed
      ureteral stents.

PMID- 26196705
TI  - Methylene Blue Doped Films of Wool Keratin with Antimicrobial Photodynamic
      Activity.
AB  - In this work, keratin films doped with different amounts of methylene blue (MB)
      were developed in order to prepare new biodegradable and biocompatible materials
      for tissue engineering and wound healing, able to exert antimicrobial
      photodynamic activity upon irradiation with visible light. Preliminary results
      indicated that the swelling ratio, as well as the MB release, increases by
      increasing the pH. Moreover, the generation of reactive oxygen species (ROS) and
      singlet oxygen can be easily triggered and controlled by a fine-tuning of the
      irradiation time and MB concentration in the films. As concerns the photodynamic
      effects on keratin, the ROS attack does not induce any significant
      photodegradation on the protein, even if a slight photo-oxidation of sulfonated
      amino acids occurs. Finally, the film with the highest MB concentration (400 MUg
      per gram of keratin) displays a significant photobactericidal activity against
      Staphylococcus aureus with a bacterial reduction that increases by increasing the
      irradiation time. In particular, the irradiation of KFMB400 film incubated with
      S. aureus at a concentration of 10(8) cfu mL(-1) determined the 99.9% killing
      rate and the killing effect increased proportionally with irradiation time. 

PMID- 26196706
TI  - Facile reduction of graphene oxide at room temperature by ammonia borane via
      salting out effect.
AB  - Nascent hydrogen as a strong reducing and environmentally benign agent can be
      used as the efficient reductant of graphene oxide. The common method is to
      dissolve metal in acid graphene oxide (GO) solution to generate nascent hydrogen
      and reduce graphene oxide. However, hydrophobic metal particles cannot contact
      well with hydrophilic GO. Lots of nascent hydrogen atoms generated surrounding
      metal particles would quickly form hydrogen instead of reducing GO, which results
      in low reduction efficiency. In this work, based on the salting effect of GO, we
      report a facile approach to synthesize graphene by mild reducing of GO using
      NH3BH3 as the reducing agent and Co3O4 as the catalyst at room temperature. This
      method exhibited higher nascent hydrogen reduction efficiency and higher C/O
      atomic ratio of reduced graphene oxide than using Fe, Zn, and Al among others.
      Also the reaction is conducted under mild conditions (room temperature),
      resulting in fewer defects. 

PMID- 26196707
TI  - Lead selenide-Titanium dioxide heteronanojunction formation by photocatalytic
      current doubling-induced two-step photodeposition technique.
AB  - PbSe quantum dots (QDs) were formed on TiO2 by a two-step photodeposition
      technique. At the first step, UV-light irradiation of TiO2 in an ethanol solution
      of H2SeO3 yields Se QDs on the TiO2 surface in a highly dispersed state
      (Se/TiO2). At the second step, UV-light irradiation of Se/TiO2 in an ethanol
      solution of Pb(ClO4)2 transforms Se QDs into several tens of nanometer-sized
      cubic deposits identified as PbSe (PbSe/TiO2) by X-ray diffraction, electronic
      absorption measurements and X-ray photoelectron spectroscopy.
      Photochronopotentiometry measurements suggested that the PbSe QDs are formed on
      TiO2 via the Pb(2+) ion-assisted reduction of Se particles.

PMID- 26196708
TI  - Facile preparation of stable palygorskite/methyl violet@SiO2 "Maya Violet"
      pigment.
AB  - Maya Blue pigment has attracted considerable attention owing to their
      extraordinary stability. The growing interest in this field has largely expanded
      the study of Maya Blue-like pigments. Inspired by Maya Blue, a stable
      palygorskite/methyl violet@SiO2 (PAL/MV@SiO2) "Maya Violet" pigment was
      fabricated via adsorption of MV by PAL, and then deposition of a layer of SiO2 on
      the surface by polycondensation of tetraethoxysilane (TEOS) in the presence of
      cetyltrimethylammonium bromide (CTAB). The weight ratio of MV to PAL is as high
      as 10%. The pigments were characterized by scanning electron microscopy and a
      variety of analytical techniques, e.g., Fourier Transform infrared spectroscopy
      and zeta potential. The results indicate that MV molecules are fixed onto the
      exterior surface, the grooves and at the entrances of the channels of PAL. The
      PAL/MV@SiO2 pigment shows excellent stability against chemical attacks, e.g., 0.1
      M HCl, 0.1 M NaOH and various organic solvents. Different from Maya Blue,
      grinding and heating treatment are virtually ineffective in improving stability
      of the PAL/MV pigment. CTAB and the SiO2 layer formed on the surface of PAL/MV
      contribute greatly to the improved stability of the pigment due to shielding
      effect. The optimal CTAB/TEOS/ammonia/H2O molar ratio for the surface
      modification of PAL/MV is 0.24/1/2.89/495.

PMID- 26196709
TI  - Organic intercalation of structure modified vermiculite.
AB  - The experiment used cationic surfactants of different chain lengths to
      intercalate structure modified vermiculites. The influences of structure
      modification, chain length and dosage of surfactants on the intercalation
      behavior of vermiculites were studied, and intercalation mechanism and features
      of interlayer chemical reactions were discussed. Results indicate that structure
      modified vermiculites with different layer charge have different intercalation
      behavior. The basal spacing of the organic intercalated modified vermiculite is
      the largest when acid concentration used in structure modification is 0.003
      mol/L, and increases with increasing the chain length and dosage of the organics.
      Molecular dynamics simulation verifies that interlayer organics align almost
      parallel to structure layer of vermiculite, with alkyl chain stretching to the
      middle of interlayer space. -N(+) groups of the three surfactants locate above
      the leached [SiO4], which has stronger interaction with interlayer organic
      cations. Electrostatic force is the main interaction force between interlayer
      organics and structure layer of vermiculite, and then is Van der Waals force, no
      chemical bond formed.

PMID- 26196710
TI  - Straightforward functionalization of breath figures: Simultaneous orthogonal host
      guest and pH-responsive interfaces.
AB  - Herein, we report the design and preparation of multireversible smart porous
      surfaces combining two different abilities. On the one hand, either neutral or
      negatively charged surfaces can be formed by formation/disruption of host-guest
      complexes. On the other hand, these surfaces have the capability of alternating
      negatively and positively charge upon complexation of a polycation. Moreover,
      these two functionalization steps were demonstrated to be reversible so that the
      initial surface can be recovered and employed again. For this purpose, first, a
      copolymer was prepared by polymerization of two different monomers, i.e. styrene
      (S) and a styrene modified with cyclodextrin (SCD) by click chemistry. Blends of
      this copolymer and polystyrene were employed to fabricate porous surfaces with
      controlled pore sizes and chemical distribution by the breath figures technique.
      More precisely, the cyclodextrin (CD) moieties, specifically located inside the
      holes of the surface, interact reversibly with adamantane end-terminated
      poly(acrylic acid) chain (Ada-PAA85). The latter served to establish
      electrostatic interaction with a polycation (poly-L-lysine, PLL), leading to
      positively charged surface. These interactions, both host-guest and
      electrostatic, can be inverted obtaining again the original surface, proving the
      full reversibility of the system.

PMID- 26196711
TI  - Glucose biosensor based on GOx/HRP bienzyme at liquid-crystal/aqueous interface.
AB  - Glucose oxidase (GOx) and horseradish peroxidase (HRP) were co-immobilized to the
      polyacrylicacid block of a poly(acrylicacid-b-4-cyanobiphenyl-4'-undecylacrylate)
      (PAA-b-LCP) copolymer in water. PAA-b-LCP was strongly anchored by the LCP block
      in 4-cyano-4'-pentylbiphenyl (5CB) which was contained in a transmission electron
      microscope (TEM) grid for glucose detection. The optimal conditions for the
      performance of the TEM grid glucose biosensor were studied in terms of the
      activity and stability of the immobilized enzymes. Glucose in water was detected
      by the 5CB changing from a planar to a homeotropic orientation, as observed
      through a polarized optical microscope. The TEM biosensor detected glucose
      concentrations at ?0.02 mM, with an optimal GOx/HRP molar ratio of 3/1. This
      glucose biosensor has characteristics of enzyme sensitivity and stability,
      reusability, the ease and selective glucose detection which may provide a new way
      of detecting glucose.

PMID- 26196712
TI  - Excellent fluoride decontamination and antibacterial efficacy of Fe-Ca-Zr hybrid
      metal oxide nanomaterial.
AB  - The aim of the present study is to develop an efficient nanomaterial for the
      removal of fluoride and disinfection of harmful bacteria in order to make water
      potable according to Environmental Protection Agency (EPA) guidelines. Hydrous
      hybrid Fe-Ca-Zr oxide nanoadsorbent presented a marked fluoride adsorption
      capacity of 250 mg/g at pH 7.0 (+/-0.1) much greater than other commercially
      accessible adsorbents for both synthetic and real water samples. The adsorption
      isotherms, Freundlich and Dubinin-Radushkevich (D-R) fitted reasonably well fine
      having high coefficient of regression values. The adsorption of fluoride was
      established well using pseudo-second-order kinetics. The fluoride loaded
      adsorbent was efficiently regenerated by using an alkali solution. Interestingly,
      the developed nanomaterial not only showed excellent fluoride removal capacity
      but also demonstrated good antibacterial activity against Escherichia coli with
      IC50 (25 MUg/mL).

PMID- 26196713
TI  - Binding of bis-(2-ethylhexyl) phthalate at the surface of hydrozincite
      nanocrystals: An example of organic molecules absorption onto nanocrystalline
      minerals.
AB  - As a contribution to understand the interactions between mineral surfaces and
      organic molecules, this study reports an accurate characterization of the bis-(2
      ethylhexyl) phthalate (DEHP)-Hydrozincite (DEHP-HY), that has been conduced
      combining the following techniques: FTIR, NMR, XAS spectroscopies and XRD. XRD
      patterns indicate that the HY is made of nanocrystals whose size is not
      influenced by the presence of DEHP. The (1)H NMR analysis of DEHP-HY samples
      points out the presence of interactions of DEHP with HY. CPMAS NMR analysis
      suggests that the interaction is operated by ester carbonyl groups while the
      aliphatic chain, as expected, is not involved. MAS and CPMAS NMR measurements,
      performed on (13)C ester carbonyl enriched DEHP, allow to demonstrate that there
      are two ester carbonyl linkage sites interacting at the HY surface: an acid site
      with a strong link and a second one with weak chemical interactions. Zn K-edge
      XAS spectroscopy demonstrates that the local atomic structure around Zn in DEHP
      HY sample remains essentially unchanged with respect to that of HY. Such a weak
      structural effect suggests that HY interaction with DEHP is limited to the
      nanoparticle surface. 

PMID- 26196714
TI  - Sulfonated methyl esters of fatty acids in aqueous solutions: Interfacial and
      micellar properties.
AB  - The interest to sulfonated methyl esters of fatty acids (SME) has been growing
      during the last decade, because these surfactants are considered as an
      environmentally friendly and renewable alternative of the linear alkyl-benzene
      sulfonates (LAS). Here, we present a quantitative study on the properties of
      aqueous SME solutions, and especially on their surface tension isotherms,
      critical micelle concentration (CMC) and its dependence on the concentration of
      added NaCl. It is demonstrated that the CMC of an ionic surfactant determined by
      electrical conductivity is insensitive to the presence of a small nonionic
      admixture, so that the CMC values determined by conductivity represent the CMC of
      the pure surfactant. Using SME as an example, we have demonstrated the
      application of a new and powerful method for determining the physicochemical
      parameters of the pure ionic surfactant by theoretical data analysis ("computer
      purification") if the used surfactant sample contains nonionic admixtures, which
      are present as a rule. This method involves fits of the experimental data for
      surface tension and conductivity by a physicochemical model based on a system of
      mass-balance, chemical-equilibrium and electric-double-layer equations, which
      allows us to determine the adsorption and micellization parameters of C12-, C14-,
      C16- and C18-SME, as well the fraction of nonionic admixtures (if any). Having
      determined these parameters, we can further predict the interfacial and
      micellization properties of the surfactant solutions, such as surface tension,
      adsorption, degree of counterion binding, and surface electric potential at every
      surfactant, salt and co-surfactant concentrations. 

PMID- 26196715
TI  - The effects of iron(II) on the kinetics of arsenic oxidation and sorption on
      manganese oxides.
AB  - In this study, As(III) oxidation kinetics by a poorly-crystalline phyllomanganate
      (delta-MnO2) in the presence and absence of dissolved Fe(II) was investigated
      using stirred-flow and batch experiments. Chemically synthetic delta-MnO2 was
      reacted with four influent solutions, containing the same As(III) concentration
      but different Fe(II) concentrations, at pH 6. The results show an initial rapid
      As(III) oxidation by delta-MnO2, which is followed by an appreciably slow
      reaction after 8h. In the presence of Fe(II), As(III) oxidation is inhibited due
      to the competitive oxidation of Fe(II) as well as the formation of Fe(III)
      (hydr)oxides on the delta-MnO2 surface. However, the sorption of As(III), As(V)
      and Mn(II) are increased, for the newly formed Fe(III)-(hydr)oxides provide
      additional sorption sites. This study suggests that the competitive oxidation of
      Fe(II) and consequently the precipitation of Fe(III) compounds on the delta-MnO2
      surface play an important role in As(III) oxidation and As sequestration.
      Understanding these processes would be helpful in developing in situ strategies
      for remediation of As-contaminated waters and soils. 

PMID- 26196716
TI  - Biologically synthesised silver nanoparticles from three diverse family of plant
      extracts and their anticancer activity against epidermoid A431 carcinoma.
AB  - HYPOTHESIS: Biological synthesis of silver nanoparticles is a cost effective
      natural process where the phytochemicals specifically phenols, flavonoids and
      terpenoids present in the plant extracts act as capping and reducing agent. Due
      to their nano size regime the silver nanoparticles may directly bind to the DNA
      of the pathogenic bacterial strains leading to higher antimicrobial activity.
      EXPERIMENT: In the current study silver nanoparticles were synthesised using
      plant extracts from different origin Cucurbita maxima (petals), Moringa oleifera
      (leaves) and Acorus calamus (rhizome). The synthesised nanoparticles were
      characterized by UV-visible spectroscopy, dynamic light scattering (DLS), X-ray
      diffraction (XRD), field emission scanning electron microscopy (Fe-SEM) and
      Fourier transform infrared spectroscopy (FTIR). FINDING: Highly crystalline,
      roughly spherical and cuboidal silver nanoparticles of 30-70 nm in size were
      synthesised. The nanoparticles provided strong antimicrobial activity against
      pathogenic strains. The effect of the synthesised nanoparticles against A431 skin
      cancer cell line was tested for their toxicity by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) dye. The IC50 values of 82.39+/-3.1,
      83.57+/-3.9 and 78.58+/-2.7 MUg/ml were calculated for silver nanoparticles
      synthesised by C. maxima, M. oleifera and A. calamus respectively.

PMID- 26196717
TI  - A novel method of synthesis of small band gap SnS nanorods and its efficient
      photocatalytic dye degradation.
AB  - A facile one pot method has been developed for synthesis of stable (xi=-37.5 mV),
      orthorhombic structured SnS nanorods capped with mercaptoacetic acid by
      precipitation method. The SnS nanorods were measured to be about 45 nm long with
      a diameter of 20 nm, as studied by transmission electron microscopy (TEM). The
      band gap of the MAA capped SnS nanorods was 1.81 eV, measured by diffused
      reflectance spectroscopy and was larger than the bulk SnS. The relative positions
      of highest valence band and lowest conduction band were determined from
      theoretical band structure calculation as 1.58 eV and -0.23 eV, respectively. The
      UV-Visible-NIR fluorescence emission spectrum of the SnS nanorods revealed
      intense emission peak at 1000 nm (1.239 eV) and weaker peaks at 935 nm, 1080 nm,
      1160 nm which is likely to be due to Sn(2+) vacancies. The as-synthesized SnS
      nanorods exhibited more than 95% sunlight induced photocatalytic degradation of
      trypan blue in 4 h, following first order kinetics with high rate of degradation
      (k) (0.0124 min(-1)). The observed dye degradation is attributable to generation
      of reactive oxygen species (ROS), confirmed from terephthalic acid assay. The ROS
      generation has been explained on the basis of interaction between photoexcited
      electrons from conduction band with molecular oxygen adhered to the surface of
      nanorods owing to favourable redox potentials of O2/O2(-) (-0.20 eV) in normal
      hydrogen electrode (NHE) scale.

PMID- 26196718
TI  - Template-free growth of well-crystalline alpha-Fe2O3 nanopeanuts with enhanced
      visible-light driven photocatalytic properties.
AB  - Well-crystalline homogeneous alpha-Fe2O3 nanopeanuts were synthesized,
      characterized and utilized as an effective photocatalysts for the photocatalytic
      degradation of toxic and harmful organic dyes, i.e. Congo red (CR), Eosin red
      (ER) and methylene blue (MB). The nanopeanuts were synthesized by facile one-step
      hydrothermal process without employing any templates and characterized in detail
      in terms of their morphological and structural properties. The detailed
      characterizations confirmed the well-crystallinity, large-scale growth and
      rhombohedral crystal structure of the synthesized nanopeanuts. Further, the
      detailed growth processes of prepared nanopeanuts were studied by examining the
      effects of reaction time, temperature and amounts of hexamethylenetetramine (HMT)
      on the shapes and sizes of the products. Thus, based on the observed experimental
      evidences, a possible growth mechanism for the formation of nanopeanuts was also
      proposed. Finally, the nanopeanuts were used as efficient visible-light driven
      photocatalyst for the photocatalytic degradation of organic dyes and the observed
      degradation rates were MB (57%)<ER (63%)<CR (93%) under visible-light
      irradiation. Interestingly, it was seen that the photocatalytic degradation of
      nanopeanuts was higher than other alpha-Fe2O3 nanostructures such as nanospindles
      and commercial alpha-Fe2O3 which revealed that the prepared alpha-Fe2O3
      nanopeanuts are excellent visible-light driven photocatalyst for the
      photocatalytic degradation of harmful and toxic organic dyes. 

PMID- 26196719
TI  - Modification of C/TiO2@MCM-41 with nickel nanoparticles for photocatalytic
      desulfurization enhancement of a diesel fuel model under visible light.
AB  - Ni metal nanoparticles were attached on the C/TiO2@MCM-41 (CTM-41) via facile and
      fast method based on dispersing of C/TiO2@MCM-41 in aqueous solution containing
      nickel ions by ultrasonic bath. Then, for the first time, the Ni ions were
      converted to Ni nanoparticles under UV light (photo-assisted deposition, PAD
      method), without using reducing agents and hydrogen gas. This process was carried
      out under the relatively mild conditions. The results showed that Ni (II) was
      reduced to Ni metallic nanoparticle in the size of about 2.7 nm on the surface of
      CTM-41 (Ni/CTM-41) with specific surface area of 754.37 m(2) g(-1). The
      photocatalytic ultra-deep desulfurization of a fuel-like n-octane containing
      dibenzothiophene (DBT) was conducted over the Ni/CTM-41 nanophotocatalyst. Using
      this method, the total sulfur content efficiently decreased under mild conditions
      in one phase and without using an oxidant. The synthesized Ni/CTM-41 (3% Ni)
      exhibited the maximum photocatalytic desulfurization of DBT for all different
      ratios of Si/Ti. In contrast, the synthesized CTM-41 (without Ni) exhibited the
      maximum photocatalytic desulfurization of DBT only for minimum ratio of Si/Ti.
      The Ni/CTM-41 was characterized by several techniques including N2 adsorption
      desorption isotherms, XRD, TEM, and atomic absorption spectroscopy techniques.
      The results confirmed that Ni was highly dispersed on the support phase. The GC
      MS analysis confirmed the photocatalytic removal of DBT. Based on the
      experimental results, it is proposed that the hydroxyl radical and hole have key
      role in the photocatalytic desulfurization process.

PMID- 26196720
TI  - Hydrothermal synthesis, phase structure, optical and photocatalytic properties of
      Zn2SnO4 nanoparticles.
AB  - Zinc stannate (Zn2SnO4 or ZTO) nanoparticles were synthesized via hydrothermal
      method using NaOH as a mineralizer. X-ray diffraction (XRD), transmission
      electron microscopy (TEM) and high-resolution transmission electron microscopy
      (HRTEM) of the synthesized ZTO nanoparticles revealed the formation of highly
      pure ZTO phase with the spinel-like structure. The nanoparticles have spherical
      shape with an average size of about 25 nm. The Raman spectrum of the sample was
      dominated by the A(1g) vibration mode of pure ZTO phase. From UV-Vis measurement,
      a band gap E(g) of 3.465 eV was determined. The photocatalytic activity of the
      ZTO nanoparticles was evaluated for the photodegradation of rhodamine B (RhB)
      under visible light irradiation. The influence of catalyst concentration and
      irradiation time on the photocatalytic process was investigated. The ZTO catalyst
      showed the best photocatalytic performance at a concentration of 0.2 g/L, and the
      photodecomposition of RhB followed first-order kinetics with a rate constant
      k=0.0249 min(-1). The ZTO-assisted photocatalytic degradation of RhB occurred via
      two competitive processes: a photocatalytic process and a photosensitized
      process. The detection of hydroxyl radicals by fluorescence measurements suggests
      that these species play an important role in the photocatalytic process.

PMID- 26196722
TI  - Games and Childhood Obesity.

PMID- 26196721
TI  - Antioxidative and cytoprotective response elicited by molybdenum nanoparticles in
      human cells.
AB  - Nanotechnology based therapeutics can offer an alternative platform in a wide
      variety of biomedical applications. Here we report novel cytotoxicity preventive
      potential of molybdenum nanoparticles (Mo NPs) in human breast (MCF-7) and
      fibrosarcoma (HT-1080) cells compromised with oxidant exposure. Physicochemical
      properties such as size, crystallinity, purity and band gap (an optical
      characteristic) of Mo NPs were characterized respectively by field emission
      transmission electron microscopy (FETEM), X-ray diffraction (XRD), energy
      dispersive spectrum (EDS) and UV-vis absorption spectroscopy. The average size of
      crystalline Mo NPs was found to be 35 nm with a band gap of 1.4 eV. Potential
      cytotoxicity of Mo NPs was evaluated by a battery of cell viability and oxidative
      stress parameters. Cell viability and oxidative stress data suggested Mo NPs to
      be reasonably non-cytotoxic. Cytotoxic preventive and GSH restoring potential of
      Mo NPs was determined against cytotoxicity and oxidative stress induced by H2O2
      (and ZnO NPs) in two cells. Mo NPs significantly increased GSH level in MCF-7 and
      HT-1080 cells, an activity that was comparable to antioxidant N-acetyl cysteine
      (NAC). GSH level was increased 1.56 times in MCF-7 cells and 1.25 times in HT
      1080 cells by 100 MUg/ml of Mo NPs relative to control cells in 24 h. End-point
      data clearly suggest that Mo NPs significantly protected cells against
      cytotoxicity induced by H2O2 and ZnO (NPs) (p<0.05). Our study warrants further
      investigation about Mo NPs that could be exploited in myriads of nanotechnology
      applications.

PMID- 26196723
TI  - [Not Available].

PMID- 26196725
TI  - Exergames, Obesity, and Youth at the National Institute for Health Innovation,
      University of Auckland, New Zealand.

PMID- 26196724
TI  - Gaming, Adiposity, and Obesogenic Behaviors Among Children.
AB  - Videogames in general have been maligned for causing obesity because of their
      inherent sedentariness, whereas exergames have been both maligned for requiring
      low levels of activity and extolled for requiring physical activity to move game
      play along. The intensity and duration of physical activity resulting from
      exergame play have shown varying results, and they have been explored for use in
      obesity treatment and prevention, primarily among children. Other videogames have
      been developed and tested to help children change their diet and physical
      activity practices with various outcomes. As a field of inquiry, we are in the
      earliest stages of understanding how, or under what circumstances, videogames can
      influence all these behavioral and health outcomes. To deal with these
      complexities, we have assembled a group of investigators who have made important,
      but diverse, contributions to this research agenda and asked them to address five
      key child obesity-related issues in a Roundtable format. Brief biosketches are
      presented at the end of this article.

PMID- 26196726
TI  - Play Yourself Healthy!

PMID- 26196727
TI  - Child Goal Setting of Dietary and Physical Activity in a Serious Videogame.
AB  - OBJECTIVE: To inform child obesity prevention programs, the current article
      identified what children thought were the most important goals, values, and
      perceived barriers related to healthy eating and physical activity (PA) within a
      serious videogame for health, "Escape from Diab" (Archimage Inc., Houston, TX).
      SUBJECTS AND METHODS: One hundred three children, 10-12 years of age, played
      "Escape from Diab." During game play the children were presented with a menu of
      goals, values, and barriers from which they selected the ones most important to
      them. The children's selections were transmitted to a central server and stored
      in a database. Frequencies were calculated and reported. RESULTS: The most
      important diet-related values and reasons for children were getting good grades
      and being healthy and fit. The most often reported barrier for fruit intake was
      that it does not fill you up, and for vegetable intake it was that availability
      at home was limited. Also, limited availability of bottled water at home was an
      often chosen barrier. PA-related important values and reasons were not missing
      school and having energy to do homework. Children preferred to limit sedentary
      activities for only 30 minutes rather than for 60 minutes. The most frequently
      mentioned barrier for reducing inactivity was "feeling too tired to do anything
      else." CONCLUSIONS: These findings provide important input for future obesity
      prevention videogames attempting to motivate children to set healthy diet and PA
      goals.

PMID- 26196728
TI  - Effects of Behavioral Contingencies on Adolescent Active Videogame Play and
      Overall Activity: A Randomized Trial.
AB  - OBJECTIVE: This study evaluated the effect of four active videogames (AVGs)
      varying in behavioral contingencies (behavior-consequence relations) on
      adolescent AVG play and overall activity levels over 4 weeks. MATERIALS AND
      METHODS: Each AVG, manufactured by SSD/Xavix((r)) (Shiseido Co. of Japan, Tokyo,
      Japan), was coded and scored for the number of positive and aversive behavioral
      contingencies within the games. "Bowling" and "Tennis" were classified as having
      "higher contingency scores," and "Boxing" and aerobic fitness training were
      classified as having "lower contingency scores." Adolescents (n=63; 11-15 years
      old; 62% male; 38% Hispanic; 44% overweight or obese) were randomized to play one
      of the four AVGs at home and recorded game play sessions in a paper log. Baseline
      and week 4 assessments were completed at home; week 1, 2, and 3 assessments were
      completed by telephone. Accelerometers were worn during baseline and weeks 1 and
      4. RESULTS: Accelerometer-measured sedentary and light activity hours/day were
      stable over time, whereas moderate-vigorous physical activity minutes/day
      increased in the higher contingency group and decreased in the lower contingency
      group (interaction effect, 6.43, P=0.024). Reported game play minutes decreased
      in both groups from week 1 to week 4 (-29.42 minutes, P=0.001). DISCUSSION: There
      was some support for the hypothesis that AVGs with more behavioral contingencies,
      compared with AVGs with fewer behavioral contingencies, result in more physical
      activity. However, overall AVG play decreased substantially after the first week.
      Further study is needed to better understand how behavioral contingencies can be
      used in AVGs to enhance their potential to provide health benefits to game
      players.

PMID- 26196729
TI  - Evaluation of Children Playing a New-Generation Motion-Sensitive Active Videogame
      by Accelerometry and Indirect Calorimetry.
AB  - OBJECTIVE: New-generation active videogames (AVGs) use motion-capture video
      cameras to connect a player's arm, leg, and body movements through three
      dimensional space to on-screen activity. We sought to determine if the whole-body
      movements required to play the AVG elicited moderate-intensity physical activity
      (PA) in children. A secondary aim was to examine the utility of using
      accelerometry to measure the activity intensity of AVG play in this age group.
      SUBJECTS AND METHODS: The PA levels of boys (n=26) and girls (n=15) 5-12 years of
      age were measured by triaxial accelerometry (n=25) or accelerometry and indirect
      calorimetry (IC) (n=16) while playing the "Kinect Adventures!" videogame for the
      Xbox Kinect (Microsoft((r)), Redmond, WA) gaming system. The experiment simulated
      a typical 20-minute in-home free-play gaming session. RESULTS: Using 10-second
      recording epochs, the average (mean+/-standard deviation) PA intensity over 20
      minutes was 4.4+/-0.9, 3.2+/-0.7, and 3.3+/-0.6 metabolic equivalents (METs) when
      estimated by IC or vertical axis (Crouter et al. intermittent lifestyle equation
      for vertical axis counts/10 seconds [Cva2RM]) and vector magnitude (Crouter et
      al. intermittent lifestyle equation for vector magnitude counts/10 seconds
      [Cvm2RM]) accelerometry. In total, 16.9+/-3.2 (IC), 10.6+/-4.5 (Cva2RM), and
      11.1+/-3.9 (Cvm2RM) minutes of game playing time were at a 3 MET intensity or
      higher. CONCLUSIONS: In this study, children played the Xbox Kinect AVG at
      moderate-intensity PA levels. The study also showed that current accelerometry
      based methods underestimated the PA of AVG play compared with IC. With proper
      guidance and recommendations for use, video motion-capture AVG systems could
      reduce sedentary screen time and increase total daily moderate PA levels for
      children. Further study of these AVG systems is warranted.

PMID- 26196730
TI  - Active Videogames and Weight Management: Is There a Future?
AB  - We evaluated the effects of an active videogame (AVG) intervention (Sony [Tokyo,
      Japan] PlayStation((r)) EyeToy((r))) compared with non-AVGs on body composition,
      physical activity, sedentary behavior, and snack food consumption among
      overweight 10-12-year-old children over 24 weeks. Our research showed a treatment
      effect on body mass index and percentage body fat in favor of the intervention
      group. There was no difference between groups for total physical activity levels,
      but there was an increase in self-reported AVG play and reductions in non-AVG
      play and snack food consumption in the intervention group. Research is needed to
      determine how to augment the effects observed in this study. 

PMID- 26196732
TI  - Coital Urinary Incontinence Induced by Impairment of the Dorsal Nerve of the
      Clitoris in Rats.
AB  - PURPOSE: We determined the effect of chronic bilateral neurectomy of the dorsal
      nerve of the clitoris on urinary parameters and sexual behavior of conscious
      female rats. MATERIALS AND METHODS: A total of 18 anesthetized virgin female
      Wistar rats were used in this study, including 11 that underwent bilateral
      neurectomy of the dorsal nerve of the clitoris and 7 that underwent sham surgery.
      Urinary parameters were determined in awake animals preoperatively, and 3 and 10
      days postoperatively. Sexual behavior was tested 14 days postoperatively to
      determine whether the females expelled urine during sexual encounters. After male
      ejaculation the females were anesthetized with urethane to record external
      urethral sphincter electromyogram activity in response to clitoris, perigenital
      skin and vaginal stimulation. Neurectomy was corroborated anatomically. RESULTS:
      Sham surgery did not significantly modify urinary parameter values. However,
      bilateral neurectomy of the dorsal nerve of the clitoris significantly increased
      voiding frequency and voiding duration (p <0.05). It did not significantly affect
      the flow rate, voided volume or voiding interval. Of females that underwent
      bilateral neurectomy of the dorsal nerve of the clitoris 67% expelled urine just
      after male ejaculation. CONCLUSIONS: These results suggest that the pudendal
      nerve is an important neural pathway in the convergence and crosstalk of female
      urogenital neural circuits, and genital deafferentation may be a causal factor of
      coital urinary incontinence. Rats with bilateral transection of the dorsal nerve
      of the clitoris may serve as an animal model of coital incontinence.

PMID- 26196731
TI  - Synthetic approaches to protein phosphorylation.
AB  - Reversible protein phosphorylation is critically important in biology and
      medicine. Hundreds of thousands of sites of protein phosphorylation have been
      discovered but our understanding of the functions of the vast majority of these
      post-translational modifications is lacking. This review describes several
      chemical and biochemical methods that are under development and in current use to
      install phospho-amino acids and their mimics site-specifically into proteins. The
      relative merits of total chemical synthesis, semisynthesis, and nonsense
      suppression strategies for studying protein phosphorylation are discussed in
      terms of technical simplicity, scope, and versatility. 

PMID- 26196733
TI  - Multi-Institutional Validation of Fundamental Inanimate Robotic Skills Tasks.
AB  - PURPOSE: Our group has previously reported the development and validation of
      FIRST (Fundamental Inanimate Robotic Skills Tasks), a series of 4 inanimate
      robotic skills tasks. Expanding on the initial validation, we now report face,
      content and construct validity of FIRST in a large multi-institutional cohort of
      experts and trainees. MATERIALS AND METHODS: A total of 96 residents, fellows and
      attending surgeons completed the FIRST exercises at participating institutions.
      Participants were classified based on previous robotic experience and task
      performance was compared across groups to establish construct validity. Face and
      content validity was assessed from participant ratings of the tasks on a 5-point
      Likert scale. RESULTS: A total of 51 novice, 22 intermediate and 23 expert
      participants with a median previous robotic experience of 0 (range 0 to 3), 10
      (range 5 to 30) and 200 cases (range 55 to 2,000), respectively (p<0.001), were
      assessed across all 4 inanimate robotic skills tasks. Expert and intermediate
      groups reliably outperformed novices (p<0.01). Experts also performed better than
      intermediates on all exercises (p<0.01). A survey of participants on their
      perceptions of the tasks yielded excellent face and content validity.
      CONCLUSIONS: We confirm robust face, content and construct validity of 4
      inanimate robotic training tasks in a large multi-institutional cohort. FIRST
      tasks are reliably able to discern among expert, intermediate and novice robotic
      surgeons. Validation data from this large multi-institutional cohort is useful as
      we incorporate these tasks into a comprehensive robotic training curriculum.

PMID- 26196734
TI  - Characterizing Early Psychosocial Functioning of Parents of Children with
      Moderate to Severe Genital Ambiguity due to Disorders of Sex Development.
AB  - PURPOSE: We examined the psychosocial characteristics of parents of children with
      disorders of sex development at early presentation to a disorders of sex
      development clinic. Parental anxiety, depression, quality of life, illness
      uncertainty and posttraumatic stress symptoms were assessed. Additionally we
      evaluated the relationship of assigned child gender to parental outcomes.
      MATERIALS AND METHODS: A total of 51 parents of children with ambiguous or
      atypical genitalia were recruited from 7 centers specializing in treatment of
      disorders of sex development. At initial assessment no child had undergone
      genitoplasty. Parents completed the Cosmetic Appearance Rating Scale, Beck
      Anxiety Inventory, Beck Depression Inventory, SF-36, Parent Perception of
      Uncertainty Scale and Impact of Event Scale-Revised. RESULTS: A large percentage
      of parents (54.5%) were dissatisfied with the genital appearance of their child,
      and a small but significant percentage reported symptoms of anxiety, depression,
      diminished quality of life, uncertainty and posttraumatic stress. Few gender
      differences emerged. CONCLUSIONS: Although many parents function well, a subset
      experience significant psychological distress around the time of diagnosis of a
      disorder of sex development in their child. Early screening to assess the need
      for psychosocial interventions is warranted.

PMID- 26196735
TI  - Treating Patients with Metastatic Castration Resistant Prostate Cancer: A
      Comprehensive Review of Available Therapies.
AB  - PURPOSE: The availability of newly approved treatment options for metastatic
      castration resistant prostate cancer is not matched with conclusive data on
      optimal sequencing strategies and resistance patterns. A comprehensive review of
      efficacy and safety data for new agents and current knowledge regarding treatment
      sequencing would enable treating physicians to make rational drug selections in
      patients with metastatic castration resistant prostate cancer. MATERIALS AND
      METHODS: We searched MEDLINE(r) and relevant congresses for data on cabazitaxel,
      docetaxel, 223radium dichloride, abiraterone, enzalutamide and sipuleucel-T,
      focusing on sequencing strategies, resistance mechanisms and biomarkers of
      response. RESULTS: Abiraterone and enzalutamide target the androgen axis with
      different mechanisms of action. Abiraterone blocks cytochrome P450 17, inhibiting
      androgen synthesis, whereas enzalutamide inhibits androgen receptor, reducing
      nuclear translocation of the androgen receptor complex and subsequent DNA
      binding. Both agents provide improved overall survival in patients with
      metastatic castration resistant prostate cancer who received prior docetaxel
      treatment and in those who are chemotherapy naive. Cabazitaxel provides improved
      overall survival in patients with metastatic castration resistant prostate cancer
      with prior docetaxel therapy. Sipuleucel-T provides improved overall survival in
      asymptomatic patients and (223)radium provides improved overall survival in
      chemotherapy naive and chemotherapy treated patients with symptomatic bone
      metastases. Selecting the correct treatment with metastatic castration resistant
      prostate cancer is complex as no head-to-head trials have been done and
      comparison between existing trials is difficult due to differences in study
      populations and a lack of validated biomarkers. Factors to consider include prior
      therapy, symptom burden, metastasis type, performance status, comorbidities,
      adverse event profiles and patient preference. Another consideration is treatment
      sequence since some agents affect responses to subsequent choices. For example,
      resistance to abiraterone or enzalutamide may result in limited responses to
      subsequent androgen targeted agents. Identifying factors predictive of resistance
      is an area of ongoing research with androgen receptor variants representing a
      good candidate. Prognostic factors for survival are also likely to be useful and
      are currently being studied. CONCLUSIONS: New therapies for metastatic castration
      resistant prostate cancer have brought new challenges with regard to treatment
      selection and sequencing. While hormonal agents provide good therapeutic
      responses, resistance may be intrinsic without prior drug exposure. Identifying
      predictors of response and relevant biomarkers will allow therapies to be more
      precisely tailored to individual patient profiles.

PMID- 26196736
TI  - Unravelling the riddle of Radix: DNA barcoding for species identification of
      freshwater snail intermediate hosts of zoonotic digeneans and estimating their
      inter-population evolutionary relationships.
AB  - Radix spp. are intermediate host snails for digenean parasites of medical and
      veterinary importance. Within this genus, species differentiation using shell and
      internal organ morphology can result in erroneous species identification, causing
      problems when trying to understand the population biology of Radix. In the
      present study, DNA barcoding, using cox1 and ITS2 sequences, identified
      populations of Radix auricularia and Radix balthica from specimens originally
      morphologically identified as Radix peregra from the UK. Assessment of cox1 and
      ITS2 as species identification markers showed that, although both markers
      differentiated species, cox1 possessed greater molecular diversity and higher
      phylogenetic resolution. Cox1 also proved useful for gaining insights into the
      evolutionary relationships of Radix species populations. Phylogenetic analysis
      and haplotype networks of cox1 indicated that R. auricularia appeared to have
      invaded the UK several times; some haplotypes forming a distinct UK specific
      clade, whilst others are more akin to those found on mainland Europe. This was in
      contrast to relationships between R. balthica populations, which had low
      molecular diversity and no distinct UK specific haplotypes, suggesting recent and
      multiple invasions from mainland Europe. Molecular techniques therefore appear to
      be crucial for distinguishing Radix spp., particularly using cox1. This barcoding
      marker also enables the population biology of Radix spp. to be explored, and is
      invaluable for monitoring the epidemiology of fluke diseases especially in the
      light of emerging diseases and food security. 

PMID- 26196737
TI  - Kv4.3-Encoded Fast Transient Outward Current Is Presented in Kv4.2 Knockout Mouse
      Cardiomyocytes.
AB  - Gradients of the fast transient outward K+ current (Ito,f) contribute to
      heterogeneity of ventricular repolarization in a number of species. Cardiac Ito,f
      levels and gradients change notably with heart disease. Human cardiac Ito,f
      appears to be encoded by the Kv4.3 pore-forming alpha-subunit plus the auxiliary
      KChIP2 beta-subunit while mouse cardiac Ito,f requires Kv4.2 and Kv4.3 alpha
      subunits plus KChIP2. Regional differences in cardiac Ito,f are associated with
      expression differences in Kv4.2 and KChIP2. Although Ito,f was reported to be
      absent in mouse ventricular cardiomyocytes lacking the Kv4.2 gene (Kv4.2-/-) when
      short depolarizing voltage pulses were used to activate voltage-gated K+
      currents, in the present study, we showed that the use of long depolarization
      steps revealed a heteropodatoxin-sensitive Ito,f (at ~40% of the wild-type
      levels). Immunohistological studies further demonstrated membrane expression of
      Kv4.3 in Kv4.2-/- cardiomyocytes. Transmural Ito,f gradients across the left
      ventricular wall were reduced by ~3.5-fold in Kv4.2-/- heart, compared to wild
      type. The Ito,f gradient in Kv4.2-/- hearts was associated with gradients in
      KChIP2 mRNA expression while in wild-type there was also a gradient in Kv4.2
      expression. In conclusion, we found that Kv4.3-based Ito,f exists in the absence
      of Kv4.2, although with a reduced transmural gradient. Kv4.2-/- mice may be a
      useful animal model for studying Kv4.3-based Ito,f as observed in humans.

PMID- 26196738
TI  - Malaria Prophylaxis Failure with Doxycycline, Central African Republic, 2014.

PMID- 26196740
TI  - Aerosol Therapy in Adults Receiving High Flow Nasal Cannula Oxygen Therapy.
AB  - BACKGROUND: High flow nasal cannula oxygen therapy (HFT) is increasingly used in
      intensive and emergency care departments. Patients suffering from respiratory
      failure, who are likely to benefit from HFT, may require aerosolized
      bronchodilators; therefore, combining nebulization with HFT may be relevant. This
      study aimed to identify the optimal settings for the implementation of
      nebulization within an adult HFT circuit. METHODS: We assessed the mass and the
      particle size distribution of the aerosol emitted from the nasal cannula
      (inhalable mass) using mesh- and jet-nebulizers placed at various positions in
      the HFT circuit. Thereafter, the most relevant combination was used to evaluate
      the mass of salbutamol delivered downstream of an anatomical model reproducing
      aerosol deposition and leakage at the nasal and pharyngeal levels (respirable
      mass). The influence of HFT flow rate (30, 45, and 60 L/min), of breathing
      pattern (quiet and respiratory distress pattern) as well as of opened and closed
      mouth breathing was assessed. RESULTS: The most efficient position was that of a
      nebulizer placed upstream from the humidification chamber (inhalable mass ranging
      from 26% to 32% of the nebulizer charge). Using a mesh nebulizer, we observed a
      respirable mass ranging from 2% to 10% of the nebulizer charge. Higher HFT flow
      rates and open mouth breathing were associated with a lower efficiency.
      Simulating respiratory distress (i.e., increasing the simulated patient
      inspiratory flow) did not hamper drug delivery as compared to a quiet breathing
      pattern. CONCLUSIONS: Placing nebulizers within a HFT circuit upstream from the
      humidification chamber may enable to deliver clinically relevant masses of
      aerosol at the cannula outlet, but more importantly downstream of the nose and
      pharynx, even in case of high patients' inspiratory flow. This method of aerosol
      therapy is expected to produce a bronchodilatatory effect to be evaluated in the
      clinical settings.

PMID- 26196739
TI  - The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription
      and Immunity to Toxoplasma gondii.
AB  - The protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses
      interferon gamma (IFN-gamma)-induced signal transducer and activator of
      transcription 1 (STAT1) activity. We exploited this well-defined host-pathogen
      interaction as the basis for a high-throughput screen, identifying nine
      transcription factors that enhance STAT1 function in the nucleus, including the
      orphan nuclear hormone receptor TLX. Expression profiling revealed that upon IFN
      gamma treatment TLX enhances the output of a subset of IFN-gamma target genes,
      which we found is dependent on TLX binding at those loci. Moreover, infection of
      TLX deficient mice with the intracellular parasite Toxoplasma results in impaired
      production of the STAT1-dependent cytokine interleukin-12 by dendritic cells and
      increased parasite burden in the brain during chronic infection. These results
      demonstrate a previously unrecognized role for this orphan nuclear hormone
      receptor in regulating STAT1 signaling and host defense and reveal that STAT1
      activity can be modulated in a context-specific manner by such "modifiers." 

PMID- 26196741
TI  - MiR-373 drives the epithelial-to-mesenchymal transition and metastasis via the
      miR-373-TXNIP-HIF1alpha-TWIST signaling axis in breast cancer.
AB  - Our previous proteomics study revealed that thioredoxin-interacting protein
      (TXNIP) was down-regulated by miR-373. However, little is known of the mechanism
      by which miR-373 decreases TXNIP to stimulate metastasis. In this study, we show
      that miR-373 promotes the epithelial-to-mesenchymal transition (EMT) in breast
      cancer. MiR-373 suppresses TXNIP by binding to the 3'UTR of TXNIP, which in turn,
      induces cancer cell EMT and metastasis. TXNIP co-expression, but not the TXNIP
      3'UTR, reverses the enhancement of EMT, migration, invasion and metastasis
      induced by miR-373. MiR-373 stimulates EMT, migration and invasion through TXNIP
      dependent reactive oxygen species (ROS) reduction. Mechanistically, miR-373 up
      regulates and activates the HIF1alpha-TWIST signaling axis via the TXNIP pathway.
      Consequently, TWIST induces miR-373 expression by binding to the promoter of the
      miR-371-373 cluster. Clinically, miR-373 is negatively associated with TXNIP and
      positively associated with HIF1alpha and TWIST, and activation of the miR-373
      TXNIP-HIF1alpha-TWIST signaling axis is correlated with a worse outcome in
      patients with breast cancer. This signaling axis may be an independent prognostic
      factor for patients with breast cancer. 

PMID- 26196742
TI  - Zebrafish (Danio rerio): A Potential Model for Toxinological Studies.
AB  - Zebrafish are an emerging basic biomedical research model that has multiple
      advantages compared with other research models. Given that biotoxins, such as
      toxins, poisons, and venoms, represent health hazards to animals and humans, a
      low-cost biological model that is highly sensitive to biotoxins is useful to
      understand the damage caused by such agents and to develop biological tests to
      prevent and reduce the risk of poisoning in potential cases of bioterrorism or
      food contamination. In this article, a narrative review of the general aspects of
      zebrafish as a model in basic biomedical research and various studies in the
      field of toxinology that have used zebrafish as a biological model are presented.
      This information will provide useful material to beginner students and
      researchers who are interested in developing toxinological studies with the
      zebrafish model. 

PMID- 26196744
TI  - Characterization of WRKY transcription factors in Solanum lycopersicum reveals
      collinearity and their expression patterns under cold treatment.
AB  - WRKY transcription factors play an important role in cold defense of plants.
      However, little information is available about the cold-responsive WRKYs in
      tomato (Solanum lycopersicum). In the present study, a complete characterization
      of this gene family was described. Eighty WRKY genes in the tomato genome were
      identified. Almost all WRKY genes contain putative stress-responsive cis-elements
      in their promoter regions. Segmental duplications contributed significantly to
      the expansion of the SlWRKY gene family. Transcriptional analysis revealed
      notable differential expression in tomato tissues and expression patterns under
      cold stress, which indicated wide functional divergence in this family. Ten WRKYs
      in tomato were strongly induced more than 2-fold during cold stress. These genes
      represented candidate genes for future functional analysis of WRKYs involved in
      the cold-related signal pathways. Our data provide valuable information about
      tomato WRKY proteins and form a foundation for future studies of these proteins,
      especially for those that play an important role in response to cold stress. 

PMID- 26196743
TI  - Adrenomedullin deficiency potentiates hyperoxic injury in fetal human pulmonary
      microvascular endothelial cells.
AB  - Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature infants
      that is characterized by alveolar simplification and decreased lung angiogenesis.
      Hyperoxia-induced oxidative stress and inflammation contributes to the
      development of BPD in premature infants. Adrenomedullin (AM) is an endogenous
      peptide with potent angiogenic, anti-oxidant, and anti-inflammatory properties.
      Whether AM regulates hyperoxic injury in fetal primary human lung cells is
      unknown. Therefore, we tested the hypothesis that AM-deficient fetal primary
      human pulmonary microvascular endothelial cells (HPMEC) will have increased
      oxidative stress, inflammation, and cytotoxicity compared to AM-sufficient HPMEC
      upon exposure to hyperoxia. Adrenomedullin gene (Adm) was knocked down in HPMEC
      by siRNA-mediated transfection and the resultant AM-sufficient and -deficient
      cells were evaluated for hyperoxia-induced oxidative stress, inflammation,
      cytotoxicity, and Akt activation. AM-deficient HPMEC had significantly increased
      hyperoxia-induced reactive oxygen species (ROS) generation and cytotoxicity
      compared to AM-sufficient HPMEC. Additionally, AM-deficient cell culture
      supernatants had increased macrophage inflammatory protein 1alpha and 1beta,
      indicating a heightened inflammatory state. Interestingly, AM deficiency was
      associated with an abrogated Akt activation upon exposure to hyperoxia. These
      findings support the hypothesis that AM deficiency potentiates hyperoxic injury
      in primary human fetal HPMEC via mechanisms entailing Akt activation. 

PMID- 26196745
TI  - Acidic environment augments FcepsilonRI-mediated production of IL-6 and IL-13 in
      mast cells.
AB  - Although blood pH is maintained in a narrow range of around pH 7.4 in living
      organisms, inflammatory loci are characterized by acidic conditions. Mast cells
      tend to reside close to the surface of the body in areas such as the mucosa and
      skin where they may be exposed to exogenous acids, and they play an important
      role in immune responses. However, little is known about the effects of
      extracellular acidification on the functions of mast cell. Here, we found that
      extracellular acidification increased the dinitrophenyl-conjugated human serum
      albumin (DNP-HSA)-induced production of interleukin (IL)-6 and IL-13 in MC/9
      cells or bone marrow-derived mouse mast cells sensitized with anti-DNP IgE.
      Extracellular acidification also inhibited migration of MC/9 cells toward DNP
      HSA. In addition, acidic pH stimulated antigen-induced activation of p38 mitogen
      activated protein kinase (MAPK) and protein kinase B (Akt). These findings
      suggest that extracellular acidification augmented antigen/IgE-induced and
      FcepsilonRI-mediated production of IL-6 and IL-13 in mast cells, and that this
      was associated with the enhancement of p38 MAPK and Akt activation. 

PMID- 26196746
TI  - Acquisition of chemoresistance to gemcitabine is induced by a loss-of-function
      missense mutation of DCK.
AB  - The anti-tumor activity of gemcitabine (GEM) has been clinically proven in
      several solid tumors, including pancreatic cancer, biliary tract cancer, urinary
      bladder cancer, and non-small cell lung cancer. However, problems remain with
      issues such as acquisition of chemoresistance against GEM. GEM is activated after
      phosphorylation by deoxycytidine kinase (DCK) inside of the cell; thus, DCK
      inactivation is one of the important mechanisms for acquisition of GEM
      resistance. We previously investigated the DCK gene in multiple GEM resistant
      cancer cell lines and identified frequent inactivating mutations. In this study,
      we identified two crucial genetic alteration in DCK. (1) A total deletion of DCK
      in RTGBC1-TKB, an acquired GEM resistant cell line derived from a gall bladder
      cancer cell line TGBC1-TKB. (2) An E197K missense alteration of DCK in MKN28, a
      gastric cancer cell line; its acquired GEM resistant cancer cell line, RMKN28,
      showed a loss of the normal E197 allele. We introduced either normal DCK or
      altered DCK_E197K into RMKN28 and proved that only the introduction of normal DCK
      restored GEM sensitivity. Furthermore, we analyzed 104 healthy volunteers and
      found that none of them carried the same base substitution observed in MKN28.
      These results strongly suggest that (1) the E197K alteration in DCK causes
      inactivation of DCK, and that (2) loss of the normal E197 allele is the crucial
      mechanism in acquisition of GEM resistance in RMKN28. 

PMID- 26196747
TI  - Effect of consecutive alternating administration (CAA) of a triple anti
      enteroviral combination on Coxsackievirus B1 neuroinfection in mice.
AB  - Currently, clinically effective antivirals for use in the treatment of
      enteroviral (EV) infections do not exist. The main reason is the development of
      drug resistance, the principle obstacle in the development of EV infection
      chemotherapy, based til now on monotherapy. The most important achievement of our
      previous studies was the development of a novel scheme for in vivo application of
      a triple combination of EV inhibitors with different modes of action against
      Coxsackievirus B (CVB) infections in mice. It consists of consecutive alternating
      administration (CAA) of the substances in the combination. Here, we tested the
      effect of the triple combination pleconaril, guanidine-HCl, and oxoglaucine (PGO)
      via CAA in newborn mice infected with a neurotropic strain of CVB1 (20 LD50 per
      mouse). This combination manifested a considerable protective effect with
      pleconaril doses of 25-200mg/kg: it decreased mortality rate (protection index,
      PI, between 31.3% and 67.7%) and increased mean survival time (MST) by 4-6days.
      Pleconaril monotherapy demonstrated activity similar to that of PGO via CAA, as
      measured by PI values, but MST values were slightly lower. However, it also
      greatly suppressed growth of infected suckling mice, especially at 200mg/kg. This
      toxic effect was avoided with CAA of PGO at pleconaril doses of 25-100mg/kg.
      Pleconaril monotherapy administered every 3days was ineffective. The PGO with CAA
      treatment course decreased infectious virus content, whereas pleconaril
      monotherapy did not. Analysis of drug-sensitivity in brain samples from CVB1
      infected mice, based on IC50 (50% inhibitory concentration) values from cell
      culture experiments, showed that the CAA course counteracted the development of
      drug resistance to pleconaril and oxoglaucine in the triple PGO combination and
      increased drug sensitivity. In contrast, pleconaril and oxoglaucine monotherapies
      resulted in drug resistance. This data clearly proves the effectiveness of the
      proposed novel approach-the CAA treatment course-for combined application of EV
      replication inhibitors. 

PMID- 26196748
TI  - A call for a new codified approach for experimentation in humans.

PMID- 26196749
TI  - Biodegradable or biocompatible polymer drug-eluting stent: a Gordian knot.

PMID- 26196750
TI  - Will this trial change my practice? A new session format that seeks to link trial
      results to the patients we treat.

PMID- 26196752
TI  - Assessment of coronary fractional flow reserve using a monorail pressure
      catheter: the first-in-human ACCESS-NZ trial.
AB  - AIMS: FFR measurements have been limited by the handling characteristics of
      pressure wire (PW) systems, and by signal drift. This first-in-human study
      evaluated the safety and efficacy of a new monorail catheter (Navvus) to assess
      coronary FFR, compared to a PW system. METHODS AND RESULTS: Resting measurements
      were acquired with both systems. After initiating IV adenosine, FFR was measured
      with the PW alone, simultaneously using both systems, and again with PW alone.
      Any zero offset of PW or Navvus was then recorded. Navvus measured FFR in all
      patients in whom a PW recording was obtained (50 of 58 patients); there were no
      complications related to Navvus. Navvus FFR correlated well with PW FFR (r=0.87,
      slope 1.0, intercept -0.02). Within PW measurement accuracy, in no cases did
      Navvus FFR classify lesion significance differently from PW FFR. PW signal drift
      was significantly greater than Navvus (0.06+/-0.12 vs. 0.02+/-0.02, p=0.014).
      CONCLUSIONS: Navvus and PW FFR correlated well. Navvus had less sensor drift.
      This new catheter-based system offers an alternative method for measuring FFR,
      with some potential advantages over PW.

PMID- 26196753
TI  - Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents
      versus durable polymer everolimus-eluting stents in patients with coronary artery
      disease: three-year follow-up of the COMPARE II (Abluminal biodegradable polymer
      biolimus-eluting stent versus durable polymer everolimus-eluting stent) trial.
AB  - AIMS: The aim of this analysis was to compare the long-term safety and efficacy
      of the biodegradable polymer biolimus-eluting stent (BES) with that of the
      durable polymer everolimus-eluting stent (EES). METHODS AND RESULTS: The COMPARE
      II study was a prospective, randomised, multicentre, all-comers trial in which
      2,707 patients were randomly allocated (2:1) to BES or EES. The pre-specified
      endpoint at three years was major adverse cardiac events (MACE), a composite of
      cardiac death, non-fatal myocardial infarction (MI), or target vessel
      revascularisation (TVR). Moreover, the combined endpoint all-cause death or MI
      was analysed as a safety, and TVR as an efficacy measure. Three-year follow-up
      was available in 2,683 patients (99.1%). At three years, MACE occurred in 213
      patients (11.9%) in the BES group and in 101 patients (11.1 %) in the EES group
      (p=0.57). The rate of the combined safety endpoint all-cause death or MI was 9.3%
      in the BES group vs. 8.4% (p=0.52), while the efficacy measure TVR was 7.6% in
      BES vs. 6.5% (p=0.27). Interestingly, definite stent thrombosis rates did not
      differ between groups (1.2% for BES vs. 0.8%, p=0.33). CONCLUSIONS: At three-year
      follow-up, MACE as well as safety and efficacy measures including stent
      thrombosis were not statistically different between the biodegradable polymer
      coated BES and the durable polymer-coated EES. ClinicalTrials.gov Identifier:
      NCT01233453.

PMID- 26196755
TI  - How should I treat a partially released JenaValveTM in the ascending aorta, whose
      feelers cannot be positioned inside the corresponding aortic sinus?

PMID- 26196754
TI  - Serial optical coherence tomography imaging of ACS-causing culprit plaques.
AB  - AIMS: The aim of this study was to understand better the mechanisms of repair of
      plaque complications causing acute coronary syndrome. METHODS AND RESULTS: We
      used OCT in the acute phase and at follow-up (one to seven months) to investigate
      the plaque healing in 10 culprit plaques: five ruptured fibrous cap (RFC) and
      five intact fibrous cap (IFC) which were not treated with stent deployment and
      caused ST-segment elevation myocardial infarction (n=8) and non-STEMI (n=2). At
      follow-up OCT, the margins of the evacuated cavity in RFC plaques showed a smooth
      surface and a morphology similar to that of baseline images, while IFC plaques
      showed a smoothened intimal border and a double layering indicating organising
      thrombus incorporated in the superficial layers of the plaque. CONCLUSIONS: In
      the months following a successfully dissolved acute thrombosis, OCT revealed that
      the cavity of RFC plaques persists and is bordered by a smooth "neointima", while
      IFC plaques showed features suggesting partial incorporation of the deepest
      layers of thrombus in the plaque.

PMID- 26196756
TI  - Will this trial change my practice? TOTAL: a randomised trial of thrombus
      aspiration in ST-elevation myocardial infarction.

PMID- 26196757
TI  - Will this trial change my practice? The Dual Antiplatelet Therapy (DAPT) study -
      12 or 30 months of dual antiplatelet therapy after drug-eluting stents.

PMID- 26196758
TI  - Will this trial change my practice? ABSORB II trial (a bioresorbable vascular
      scaffold versus drug-eluting stent in coronary disease).

PMID- 26196759
TI  - Influenza A Viruses of Human Origin in Swine, Brazil.
AB  - The evolutionary origins of the influenza A(H1N1)pdm09 virus that caused the
      first outbreak of the 2009 pandemic in Mexico remain unclear, highlighting the
      lack of swine surveillance in Latin American countries. Although Brazil has one
      of the largest swine populations in the world, influenza was not thought to be
      endemic in Brazil's swine until the major outbreaks of influenza A(H1N1)pdm09 in
      2009. Through phylogenetic analysis of whole-genome sequences of influenza
      viruses of the H1N1, H1N2, and H3N2 subtypes collected in swine in Brazil during
      2009-2012, we identified multiple previously uncharacterized influenza viruses of
      human seasonal H1N2 and H3N2 virus origin that have circulated undetected in
      swine for more than a decade. Viral diversity has further increased in Brazil
      through reassortment between co-circulating viruses, including A(H1N1)pdm09. The
      circulation of multiple divergent hemagglutinin lineages challenges the design of
      effective cross-protective vaccines and highlights the need for additional
      surveillance. 

PMID- 26196760
TI  - Control of the wrinkle structure on surface-reformed poly(dimethylsiloxane) via
      ion-beam bombardment.
AB  - We investigated the surface reformation of poly(dimethylsiloxane) (PDMS)
      elastomers by means of ion beam bombardment for fabricating wrinkle structures.
      Oxidation on the PDMS surface formed a silica-like outer layer that interacted
      with the inner PDMS layer, leading to the formation of wrinkle structures that
      minimized the combined bending energy of the outer layer and stretching energy of
      the inner layer. In addition, we controlled the amplitude and period of the
      wrinkle structures by adjusting the PDMS annealing temperature. As the PDMS
      annealing temperature was increased, the amplitude and period of the wrinkles
      formed by IB irradiation changed from 604.35 to 69.01 nm and from 3.07 to 0.80
      MUm, respectively. 

PMID- 26196761
TI  - Glycerol Ether Synthesis: A Bench Test for Green Chemistry Concepts and
      Technologies.

PMID- 26196762
TI  - Probing questions.

PMID- 26196763
TI  - Curation of chemogenomics data.

PMID- 26196766
TI  - Voices of chemical biology.

PMID- 26196765
TI  - Probing the epigenome.

PMID- 26196773
TI  - Biosynthesis: Leading the way to RiPPs.

PMID- 26196774
TI  - The evolutionary psychology of mate selection in Morocco : A multivariate
      analysis.
AB  - Patterns of mate preference in Morocco are investigated in order to test whether
      they support hypotheses advanced by David Buss and other evolutionary
      psychologists. Because of the custom of cousin marriage in Morocco, a
      multivariate model that included cosocialization data was developed for the
      purpose of testing the Westermarck hypothesis of inbreeding avoidance. Hence, two
      previously separate domains of research are unified in one design that permits
      the further exploration of questions pertaining to the domain specificity of
      psychological mechanisms. Multiple independent mate choice predictors were
      identified using logistic regression analysis. Results support the Westermarck
      hypothesis of inbreeding avoidance. Sleeping in the same room during childhood
      was found in both sexes to produce an aversion to marriage. Other evidence
      suggests that aversion to inbreeding extends further among females than males in
      that females but not males show an aversion to marriage to related individuals
      with whom they had daily social contact in early childhood. The evolutionary
      prediction that females differ from males concerning resource holding capacity
      was also supported. Females showed a preference for males whom they judged to
      have higher social status than theirs, while this criterion was unimportant for
      males. The predicted sex difference in preferred age of marriage partner was also
      supported. Contrary to previous findings, the predicted difference between the
      sexes with regard to physical attractiveness was not supported. 

PMID- 26196775
TI  - Matrilateral biases in the investment of aunts and uncles : A consequence and
      measure of paternity uncertainty.
AB  - In a study of the kin investment of aunts and uncles we show that the laterality
      effect expected as a result of paternity uncertainty is statistically reliable
      but somewhat smaller than the sex effect. Matrilateral aunts invest significantly
      more than patrilateral aunts, and the same is true for uncles. Regardless of
      laterality, however, aunts invest significantly more than uncles. Multivariate
      controls show that the matrilateral bias is fully independent of any age or
      distance confounds that might result from sex differences in age at marriage or
      dispersal. We discuss our results in relation to recent findings on the kin
      investment of grandparents (Euler and Weitzel 1996). In addition, we propose a
      simple method for estimating the level of paternity uncertainty from kin
      investment data; application of this method to our data on aunts and uncles
      suggests that between 13% and 20% of children are not the offspring of their
      putative father. Our parallel analyses of Euler and Weitzel's (1996) data on
      grandparental investment suggest a similar estimate, that paternity uncertainty
      lies between 9% and 17%. 

PMID- 26196776
TI  - In search of behavioral individuality.
AB  - Living things are not created identical: In sexually reproducing species,
      individuals-except monozygotic twins-are different. Although widely acknowledged,
      behavioral individuality has received relatively little empirical or theoretical
      attention. Yet it seems likely that research focusing on individual differences
      will yield important insights for evolutionarily minded students of behavioral
      biology, including those interested in better understanding Homo sapiens. 

PMID- 26196764
TI  - The promise and peril of chemical probes.

PMID- 26196777
TI  - Verse form : A pilot study in the epidemiology of representations.
AB  - This paper presents a pilot study in the "epidemiological" program for cultural
      research put forward by Dan Sperber. Theory is offered to argue that verse form
      is so disabling that its worldwide distribution must be explained by functions
      other than the broad communicative, or ideological, power traditionally
      attributed to it. The theoretical case is confirmed by numerical data showing
      that in matched texts of English prose and verse the latter contain words of a
      lower mean length (measured in syllables). Candidate hypotheses for the
      epidemiology of verse are offered, including design for mnemonic properties, the
      registration of differences in verbal intelligence, the presentation of gestures
      of commitment, and the introduction of levels of quasi-randomness that lead to an
      impression of semantic richness and the illusion of profound and powerful
      communication. 

PMID- 26196778
TI  - Lead concentrations in whole blood, serum, saliva and house dust in samples
      collected at two time points (12 months apart) in Santo Amaro, BA, Brazil.
AB  - Whole Blood Lead Level (BLL) is the main marker used to verify lead
      contamination. The present study explores how BLL is associated with lead
      concentrations in serum, saliva and house dust. Samples were collected twice from
      Santo Amaro, BA, Brazil, a region that was contaminated by a lead smelter in the
      past; a time interval of 12 months was allowed between the two collections. It is
      noteworthy that the following measures have recently been taken to diminish
      exposure of the population to lead: streets have been paved with asphalt, and
      educational campaigns have been launched to reduce exposure to contaminated dust.
      RESULTS: Compared with the first time point, all the samples collected at the
      second time point contained lower lead concentration (p<0.05), which suggested
      that the adopted measures effectively reduced exposure of the population to lead
      present in contaminated soil and dust. Statistically significant correlations
      only existed between lead in blood collected in the first year and lead in blood
      collected in the second year (Spearman's r=0.55; p<0.0001; n=62), and lead in
      house dust collected in the first year and lead in house dust collected in the
      second year (Spearman's r=0.5; p<0.0001; n=59). CONCLUSIONS: Results support the
      validity of lead determination in blood and in house dust to assess lead exposure
      over time. However, lead in blood and lead in dust did not correlate with lead in
      serum or lead in saliva.

PMID- 26196615
TI  - Search for New Phenomena in Dijet Angular Distributions in Proton-Proton
      Collisions at sqrt[s]=8 TeV Measured with the ATLAS Detector.
AB  - A search for new phenomena in LHC proton-proton collisions at a center-of-mass
      energy of sqrt[s]=8 TeV was performed with the ATLAS detector using an integrated
      luminosity of 17.3 fb^{-1}. The angular distributions are studied in events with
      at least two jets; the highest dijet mass observed is 5.5 TeV. All angular
      distributions are consistent with the predictions of the standard model. In a
      benchmark model of quark contact interactions, a compositeness scale below 8.1
      TeV in a destructive interference scenario and 12.0 TeV in a constructive
      interference scenario is excluded at 95% C.L.; median expected limits are 8.9 TeV
      for the destructive interference scenario and 14.1 TeV for the constructive
      interference scenario.

PMID- 26196787
TI  - Fluctuation-Induced Forces in Nonequilibrium Diffusive Dynamics.
AB  - Fluctuations in nonequilibrium steady states generically lead to power law decay
      of correlations for conserved quantities. Embedded bodies which constrain
      fluctuations, in turn, experience fluctuation induced forces. We compute these
      forces for the simple case of parallel slabs in a driven diffusive system. Our
      model calculations show that the force falls off with slab separation d as kBT/d
      (at temperature T, and in all spatial dimensions) but can be attractive or
      repulsive. Unlike the equilibrium Casimir force, the force amplitude is
      nonuniversal and explicitly depends on dynamics. The techniques introduced can be
      used to study pressure and fluctuation induced forces in a broad class of
      nonequilibrium systems.

PMID- 26196786
TI  - Thermodynamics of Nonadditive Systems.
AB  - The usual formulation of thermodynamics is based on the additivity of macroscopic
      systems. However, there are numerous examples of macroscopic systems that are not
      additive, due to the long-range character of the interaction among the
      constituents. We present here an approach in which nonadditive systems can be
      described within a purely thermodynamics formalism. The basic concept is to
      consider a large ensemble of replicas of the system where the standard
      formulation of thermodynamics can be naturally applied and the properties of a
      single system can be consequently inferred. After presenting the approach, we
      show its implementation in systems where the interaction decays as 1/r(alpha) in
      the interparticle distance r, with alpha smaller than the embedding dimension d,
      and in the Thirring model for gravitational systems.

PMID- 26196784
TI  - Solid State Spin-Wave Quantum Memory for Time-Bin Qubits.
AB  - We demonstrate the first solid-state spin-wave optical quantum memory with on
      demand read-out. Using the full atomic frequency comb scheme in a Pr(3+):Y2SiO5
      crystal, we store weak coherent pulses at the single-photon level with a signal
      to-noise ratio >10. Narrow-band spectral filtering based on spectral hole burning
      in a second Pr(3+):Y2SiO5 crystal is used to filter out the excess noise created
      by control pulses to reach an unconditional noise level of (2.0+/-0.3)*10(-3)
      photons per pulse. We also report spin-wave storage of photonic time-bin qubits
      with conditional fidelities higher than achievable by a measure and prepare
      strategy, demonstrating that the spin-wave memory operates in the quantum regime.
      This makes our device the first demonstration of a quantum memory for time-bin
      qubits, with on-demand read-out of the stored quantum information. These results
      represent an important step for the use of solid-state quantum memories in
      scalable quantum networks.

PMID- 26196783
TI  - Observation of Pair Condensation in the Quasi-2D BEC-BCS Crossover.
AB  - The condensation of fermion pairs lies at the heart of superfluidity. However,
      for strongly correlated systems with reduced dimensionality the mechanisms of
      pairing and condensation are still not fully understood. In our experiment we use
      ultracold atoms as a generic model system to study the phase transition from a
      normal to a condensed phase in a strongly interacting quasi-two-dimensional Fermi
      gas. Using a novel method, we obtain the in situ pair momentum distribution of
      the strongly interacting system and observe the emergence of a low-momentum
      condensate at low temperatures. By tuning temperature and interaction strength,
      we map out the phase diagram of the quasi-2D BEC-BCS crossover. 

PMID- 26196782
TI  - Discussion of "Evidence-based Health Informatics: How Do We Know What We Know?".
AB  - This article is part of a For-Discussion-Section of Methods of Information in
      Medicine about the paper "Evidence-based Health Informatics: How Do We Know What
      We Know?" written by Elske Ammenwerth [1]. It is introduced by an editorial. This
      article contains the combined commentaries invited to independently comment on
      the Ammenwerth paper. In subsequent issues the discussion can continue through
      letters to the editor. With these comments on the paper "Evidence-based Health
      Informatics: How do we know what we know?", written by Elske Ammenwerth [1], the
      journal seeks to stimulate a broad discussion on the challenges of evaluating
      information processing and information technology in health care. An
      international group of experts has been invited by the editor of Methods to
      comment on this paper. Each of the invited commentaries forms one section of this
      paper. 

PMID- 26196779
TI  - Associations between exposure to ambient benzene and PM(2.5) during pregnancy and
      the risk of selected birth defects in offspring.
AB  - OBJECTIVE: A growing number of studies have investigated the association between
      air pollution and the risk of birth defects, but results are inconsistent. The
      objective of this study was to examine whether maternal exposure to ambient PM2.5
      or benzene increases the risk of selected birth defects in Florida. METHODS: We
      conducted a retrospective cohort study of singleton infants born in Florida from
      2000 to 2009. Isolated and non-isolated birth defect cases of critical congenital
      heart defects, orofacial clefts, and spina bifida were identified from the
      Florida Birth Defects Registry. Estimates of maternal exposures to PM2.5 and
      benzene for all case and non-case pregnancies were derived by aggregation of
      ambient measurement data, obtained from the US Environmental Protection Agency
      Air Quality System, during etiologically relevant time windows. Multivariable
      Poisson regression was used to estimate adjusted prevalence ratios (aPRs) and 95%
      confidence intervals (CIs) for each quartile of air pollutant exposure. RESULTS:
      Compared to the first quartile of PM2.5 exposure, higher levels of exposure were
      associated with an increased risk of non-isolated truncus arteriosus (aPR4th
      Quartile, 8.80; 95% CI, 1.11-69.50), total anomalous pulmonary venous return
      (aPR2nd Quartile, 5.00; 95% CI, 1.10-22.84), coarctation of the aorta (aPR4th
      Quartile, 1.72; 95% CI, 1.15-2.57; aPR3rd Quartile, 1.60; 95% CI, 1.07-2.41),
      interrupted aortic arch (aPR4th Quartile, 5.50; 95% CI, 1.22-24.82), and isolated
      and non-isolated any critical congenital heart defect (aPR3rd Quartile, 1.13; 95%
      CI, 1.02-1.25; aPR4th Quartile, 1.33; 95% CI, 1.07-1.65). Mothers with the
      highest level of exposure to benzene were more likely to deliver an infant with
      an isolated cleft palate (aPR4th Quartile, 1.52; 95% CI, 1.13-2.04) or any
      orofacial cleft (aPR4th Quartile, 1.29; 95% CI, 1.08-1.56). An inverse
      association was observed between exposure to benzene and non-isolated pulmonary
      atresia (aPR4th Quartile, 0.19; 95% CI, 0.04-0.84). CONCLUSION: Our results
      suggest a few associations between exposure to ambient PM2.5 or benzene and
      specific birth defects in Florida. However, many related comparisons showed no
      association. Hence, it remains unclear whether associations are clinically
      significant or can be causally related to air pollution exposures.

PMID- 26196785
TI  - Coherent Spin Control at the Quantum Level in an Ensemble-Based Optical Memory.
AB  - Long-lived quantum memories are essential components of a long-standing goal of
      remote distribution of entanglement in quantum networks. These can be realized by
      storing the quantum states of light as single-spin excitations in atomic
      ensembles. However, spin states are often subjected to different dephasing
      processes that limit the storage time, which in principle could be overcome using
      spin-echo techniques. Theoretical studies suggest this to be challenging due to
      unavoidable spontaneous emission noise in ensemble-based quantum memories. Here,
      we demonstrate spin-echo manipulation of a mean spin excitation of 1 in a large
      solid-state ensemble, generated through storage of a weak optical pulse. After a
      storage time of about 1 ms we optically read-out the spin excitation with a high
      signal-to-noise ratio. Our results pave the way for long-duration optical quantum
      storage using spin-echo techniques for any ensemble-based memory. 

PMID- 26196780
TI  - Modeling spatial effects of PM(2.5) on term low birth weight in Los Angeles
      County.
AB  - Air pollution epidemiological studies suggest that elevated exposure to fine
      particulate matter (PM2.5) is associated with higher prevalence of term low birth
      weight (TLBW). Previous studies have generally assumed the exposure-response of
      PM2.5 on TLBW to be the same throughout a large geographical area. Health effects
      related to PM2.5 exposures, however, may not be uniformly distributed spatially,
      creating a need for studies that explicitly investigate the spatial distribution
      of the exposure-response relationship between individual-level exposure to PM2.5
      and TLBW. Here, we examine the overall and spatially varying exposure-response
      relationship between PM2.5 and TLBW throughout urban Los Angeles (LA) County,
      California. We estimated PM2.5 from a combination of land use regression (LUR),
      aerosol optical depth from remote sensing, and atmospheric modeling techniques.
      Exposures were assigned to LA County individual pregnancies identified from
      electronic birth certificates between the years 1995-2006 (N=1,359,284) provided
      by the California Department of Public Health. We used a single pollutant
      multivariate logistic regression model, with multilevel spatially structured and
      unstructured random effects set in a Bayesian framework to estimate global and
      spatially varying pollutant effects on TLBW at the census tract level. Overall,
      increased PM2.5 level was associated with higher prevalence of TLBW county-wide.
      The spatial random effects model, however, demonstrated that the exposure
      response for PM2.5 and TLBW was not uniform across urban LA County. Rather, the
      magnitude and certainty of the exposure-response estimates for PM2.5 on log odds
      of TLBW were greatest in the urban core of Central and Southern LA County census
      tracts. These results suggest that the effects may be spatially patterned, and
      that simply estimating global pollutant effects obscures disparities suggested by
      spatial patterns of effects. Studies that incorporate spatial multilevel modeling
      with random coefficients allow us to identify areas where air pollutant effects
      on adverse birth outcomes may be most severe and policies to further reduce air
      pollution might be most effective. 

PMID- 26196781
TI  - Autotaxin and Endotoxin-Induced Acute Lung Injury.
AB  - Acute Lung Injury (ALI) is a life-threatening, diffuse heterogeneous lung injury
      characterized by acute onset, pulmonary edema and respiratory failure.
      Lipopolysaccharide (LPS) is a common cause of both direct and indirect lung
      injury and when administered to a mouse induces a lung phenotype exhibiting some
      of the clinical characteristics of human ALI. Here, we report that LPS inhalation
      in mice results in increased bronchoalveolar lavage fluid (BALF) levels of
      Autotaxin (ATX, Enpp2), a lysophospholipase D largely responsible for the
      conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA) in
      biological fluids and chronically inflamed sites. In agreement, gradual increases
      were also detected in BALF LPA levels, following inflammation and pulmonary
      edema. However, genetic or pharmacologic targeting of ATX had minor effects in
      ALI severity, suggesting no major involvement of the ATX/LPA axis in acute
      inflammation. Moreover, systemic, chronic exposure to increased ATX/LPA levels
      was shown to predispose to and/or to promote acute inflammation and ALI unlike
      chronic inflammatory pathophysiological situations, further suggesting a
      differential involvement of the ATX/LPA axis in acute versus chronic pulmonary
      inflammation. 

PMID- 26196788
TI  - Frequency Ratio of (199)Hg and (87)Sr Optical Lattice Clocks beyond the SI Limit.
AB  - We report on a frequency ratio measurement of a (199)Hg-based optical lattice
      clock referencing a (87)Sr-based clock. Evaluations of lattice light shift,
      including atomic-motion-dependent shift, enable us to achieve a total systematic
      uncertainty of 7.2*10(-17) for the Hg clock. The frequency ratio is measured to
      be nuHg/nuSr=2.629 314 209 898 909 60(22) with a fractional uncertainty of
      8.4*10(-17), which is smaller than the uncertainty of the realization of the
      International System of Units (SI) second, i.e., the SI limit.

PMID- 26196789
TI  - Thermodynamics of Asymptotically Conical Geometries.
AB  - We study the thermodynamical properties of a class of asymptotically conical
      geometries known as "subtracted geometries." We derive the mass and angular
      momentum from the regulated Komar integral and the Hawking-Horowitz prescription
      and show that they are equivalent. By deriving the asymptotic charges, we show
      that the Smarr formula and the first law of thermodynamics hold. We also propose
      an analog of Christodulou-Ruffini inequality. The analysis can be generalized to
      other asymptotically conical geometries. 

PMID- 26196791
TI  - Direct Detection Phenomenology in Models Where the Products of Dark Matter
      Annihilation Interact with Nuclei.
AB  - We investigate the direct detection phenomenology of a class of dark matter (DM)
      models in which DM does not directly interact with nuclei, but rather, the
      products of its annihilation do. When these annihilation products are very light
      compared to the DM mass, the scattering in direct detection experiments is
      controlled by relativistic kinematics. This results in a distinctive recoil
      spectrum, a nonstandard and/or even absent annual modulation, and the ability to
      probe DM masses as low as a ~10  MeV. We use current LUX data to show that
      experimental sensitivity to thermal relic annihilation cross sections has already
      been reached in a class of models. Moreover, the compatibility of dark matter
      direct detection experiments can be compared directly in Emin space without
      making assumptions about DM astrophysics, mass, or scattering form factors.
      Lastly, when DM has direct couplings to nuclei, the limit from annihilation to
      relativistic particles in the Sun can be stronger than that of conventional
      nonrelativistic direct detection by more than 3 orders of magnitude for masses in
      a 2-7 GeV window.

PMID- 26196790
TI  - Dark Matter Search Results from the PICO-2L C3F8 Bubble Chamber.
AB  - New data are reported from the operation of a 2 liter C3F8 bubble chamber in the
      SNOLAB underground laboratory, with a total exposure of 211.5 kg days at four
      different energy thresholds below 10 keV. These data show that C3F8 provides
      excellent electron-recoil and alpha rejection capabilities at very low
      thresholds. The chamber exhibits an electron-recoil sensitivity of <3.5*10(-10)
      and an alpha rejection factor of >98.2%. These data also include the first
      observation of a dependence of acoustic signal on alpha energy. Twelve single
      nuclear recoil event candidates were observed during the run. The candidate
      events exhibit timing characteristics that are not consistent with the hypothesis
      of a uniform time distribution, and no evidence for a dark matter signal is
      claimed. These data provide the most sensitive direct detection constraints on
      WIMP-proton spin-dependent scattering to date, with significant sensitivity at
      low WIMP masses for spin-independent WIMP-nucleon scattering.

PMID- 26196793
TI  - Periodic Interference Structures in the Timelike Proton Form Factor.
AB  - An intriguing and elusive feature of the timelike hadron form factor is the
      possible presence of an imaginary part associated to rescattering processes. We
      find evidence of that in the recent and precise data on the proton timelike form
      factor measured by the BABAR Collaboration. By plotting these data as a function
      of the 3-momentum of the relative motion of the final proton and antiproton, a
      systematic sinusoidal modulation is highlighted in the near-threshold region. Our
      analysis attributes this pattern to rescattering processes at a relative distance
      of 0.7-1.5 fm between the centers of the forming hadrons. This distance implies a
      large fraction of inelastic processes in pp interactions, and a large imaginary
      part in the related e(+)e(-)->pp reaction because of unitarity.

PMID- 26196796
TI  - Torsional Motion of the Chromophore Catechol following the Absorption of
      Ultraviolet Light.
AB  - The ability to probe energy flow in molecules, following the absorption of
      ultraviolet light, is crucial to unraveling photophysical phenomena. Here we
      excite a coherent superposition of vibrational states in the first excited
      electronic state (S1) in catechol, resulting in a vibrational wave packet. The
      observed quantum beats, assigned to superpositions of the low-frequency, and
      strongly mixed, O-H torsional mode tau2, elegantly demonstrate how changes in
      geometry upon photoionization from the S1 state to the ground state of the cation
      (D0) enables one to probe energy flow at the very early stages of photoexcitation
      in this biological chromophore.

PMID- 26196799
TI  - Ultrasensitive Ultrafast Vibrational Spectroscopy Employing the Near Field of
      Gold Nanoantennas.
AB  - We introduce a novel method to perform nonlinear vibrational spectroscopy on
      nanoscale volumes. Our technique uses the intense near field of infrared
      nanoantennas to amplify the nonlinear vibrational signals of molecules located in
      the vicinity of the antenna surface. We demonstrate the capabilities of the
      method by performing infrared pump-probe spectroscopy and two-dimensional
      infrared spectroscopy on 5 nm layers of polymethylmetacrylate. In these
      experiments we observe enhancement factors of the nonlinear signals of more than
      4 orders of magnitude. We discuss the mechanism underlying the amplification
      process as well as strategies for further increasing the sensitivity of the
      technique. 

PMID- 26196798
TI  - Coherent Control of Bond Making.
AB  - We demonstrate coherent control of bond making, a milestone on the way to
      coherent control of photoinduced bimolecular chemical reactions. In strong-field
      multiphoton femtosecond photoassociation experiments, we find the yield of
      detected magnesium dimer molecules to be enhanced for positively chirped pulses
      and suppressed for negatively chirped pulses. Our ab initio model shows that
      control is achieved by purification combined with chirp-dependent Raman
      transitions. Experimental closed-loop phase optimization using a learning
      algorithm yields an improved pulse that utilizes vibrational coherent dynamics in
      addition to chirp-dependent Raman transitions. Our results show that coherent
      control of binary photoreactions is feasible even under thermal conditions. 

PMID- 26196795
TI  - First Direct Determination of the Superallowed beta-Decay QEC Value for (14)O.
AB  - We report the first direct measurement of the (14)O superallowed Fermi beta-decay
      QEC value, the last of the so-called "traditional nine" superallowed Fermi beta
      decays to be measured with Penning trap mass spectrometry. (14)O, along with the
      other low-Z superallowed beta emitter, (10)C, is crucial for setting limits on
      the existence of possible scalar currents. The new ground state QEC value,
      5144.364(25) keV, when combined with the energy of the 0(+) daughter state,
      Ex(0(+))=2312.798(11)  keV [F. Ajzenberg-Selove, Nucl. Phys. A523, 1 (1991)],
      provides a new determination of the superallowed beta-decay QEC value,
      QEC(sa)=2831.566(28)  keV, with an order of magnitude improvement in precision,
      and a similar improvement to the calculated statistical rate function f. This is
      used to calculate an improved Ft value of 3073.8(2.8) s.

PMID- 26196797
TI  - First Measurement of the Atomic Electric Dipole Moment of (225)Ra.
AB  - The radioactive radium-225 ((225)Ra) atom is a favorable case to search for a
      permanent electric dipole moment. Because of its strong nuclear octupole
      deformation and large atomic mass, (225)Ra is particularly sensitive to
      interactions in the nuclear medium that violate both time-reversal symmetry and
      parity. We have developed a cold-atom technique to study the spin precession of
      (225)Ra atoms held in an optical dipole trap, and demonstrated the principle of
      this method by completing the first measurement of its atomic electric dipole
      moment, reaching an upper limit of |d((225)Ra)|<5.0*10(-22)  e cm (95%
      confidence).

PMID- 26196800
TI  - Metastable Aluminum Atoms Floating on the Surface of Helium Nanodroplets.
AB  - Metal atoms have proved to be sensitive probes of the properties of superfluid
      helium nanodroplets. To date, all experiments on the doping of helium droplets
      have concentrated on the attachment of metal atoms in their ground electronic
      states. Here we report the first examples of metal atoms in excited states
      becoming attached to helium nanodroplets. The atoms in question are aluminum, and
      they have been generated by laser ablation in a metastable quartet state, which
      attaches to and remains on the surface of helium droplets. Evidence for a surface
      location comes from electronic spectra, which consist of very narrow absorption
      profiles that show very small spectral shifts. Supporting ab initio calculations
      show there to be an energy incentive for a metastable Al atom to remain on the
      surface of a helium droplet rather than move to the interior. The results suggest
      that helium droplets may provide a method for the capture and transport of
      metastable excited atomic and molecular species. 

PMID- 26196794
TI  - Observation of Lambda(4)H Hyperhydrogen by Decay-Pion Spectroscopy in Electron
      Scattering.
AB  - At the Mainz Microtron MAMI, the first high-resolution pion spectroscopy from
      decays of strange systems was performed by electron scattering off a (9)Be target
      in order to study the Lambda binding energy of light hypernuclei. Positively
      charged kaons were detected by a short-orbit spectrometer with a broad momentum
      acceptance at 0 degrees  forward angles with respect to the beam, efficiently
      tagging the production of strangeness in the target nucleus. Coincidentally,
      negatively charged decay pions were detected by two independent high-resolution
      spectrometers. About 10(3) pionic weak decays of hyperfragments and hyperons were
      observed. The pion momentum distribution shows a monochromatic peak at ppi~133 
      MeV/c, corresponding to the unique signature for the two-body decay of
      hyperhydrogen Lambda(4)H->(4)He+pi(-), stopped inside the target. Its Lambda
      binding energy was determined to be BLambda=2.12+/-0.01  (stat)+/-0.09  (syst)MeV
      with respect to the (3)H+Lambda mass.

PMID- 26196801
TI  - Coherent Generation of Nonclassical Light on Chip via Detuned Photon Blockade.
AB  - The on-chip generation of nonclassical states of light is a key requirement for
      future optical quantum hardware. In solid-state cavity quantum electrodynamics,
      such nonclassical light can be generated from self-assembled quantum dots
      strongly coupled to photonic crystal cavities. Their anharmonic strong light
      matter interaction results in large optical nonlinearities at the single photon
      level, where the admission of a single photon into the cavity may enhance (photon
      tunneling) or diminish (photon blockade) the probability for a second photon to
      enter the cavity. Here, we demonstrate that detuning the cavity and quantum-dot
      resonances enables the generation of high-purity nonclassical light from strongly
      coupled systems. For specific detunings we show that not only the purity but also
      the efficiency of single-photon generation increases significantly, making high
      quality single-photon generation by photon blockade possible with current state
      of-the-art samples. 

PMID- 26196802
TI  - Environment-Assisted Speed-up of the Field Evolution in Cavity Quantum
      Electrodynamics.
AB  - We measure the quantum speed of the state evolution of the field in a weakly
      driven optical cavity QED system. To this end, the mode of the electromagnetic
      field is considered as a quantum system of interest with a preferential coupling
      to a tunable environment: the atoms. By controlling the environment, i.e.,
      changing the number of atoms coupled to the optical cavity mode, an environment
      assisted speed-up is realized: the quantum speed of the state repopulation in the
      optical cavity increases with the coupling strength between the optical cavity
      mode and this non-Markovian environment (the number of atoms). 

PMID- 26196803
TI  - Hyperbolic Plasmons and Topological Transitions Over Uniaxial Metasurfaces.
AB  - We explore the unusual electromagnetic response of ultrathin anisotropic sigma
      near-zero uniaxial metasurfaces, demonstrating extreme topological transitions-
      from closed elliptical to open hyperbolic--for surface plasmon propagation,
      associated with a dramatic tailoring of the local density of states. The proposed
      metasurfaces may be implemented using nanostructured graphene monolayers and open
      unprecedented venues for extreme light confinement and unusual propagation and
      guidance, combined with large tunability via electric bias.

PMID- 26196804
TI  - Stability Limits of Capillary Bridges: How Contact Angle Hysteresis Affects
      Morphology Transitions of Liquid Microstructures.
AB  - The equilibrium shape of a drop in contact with solid surfaces can undergo
      continuous or discontinuous transitions upon changes in either drop volume or
      surface energies. In many instances, such transitions involve the motion of the
      three-phase contact line and are thus sensitive to contact angle hysteresis.
      Using a combination of electrowetting-based experiments and numerical
      calculations, we demonstrate for a generic sphere-plate confinement geometry how
      contact angle hysteresis affects the mechanical stability of competing
      axisymmetric and nonaxisymmetric drop conformations and qualitatively changes the
      character of transitions between them. 

PMID- 26196806
TI  - Extending the Nonlinear-Beam-Dynamics Concept of 1D Fixed Points to 2D Fixed
      Lines.
AB  - The origin of nonlinear dynamics traces back to the study of the dynamics of
      planets with the seminal work of Poincare at the end of the nineteenth century:
      Les Methodes Nouvelles de la Mecanique Celeste, Vols. 1-3 (Gauthier Villars,
      Paris, 1899). In his work he introduced a methodology fruitful for investigating
      the dynamical properties of complex systems, which led to the so-called "Poincare
      surface of section," which allows one to capture the global dynamical properties
      of a system, characterized by fixed points and separatrices with respect to
      regular and chaotic motion. For two-dimensional phase space (one degree of
      freedom) this approach has been extremely useful and applied to particle
      accelerators for controlling their beam dynamics as of the second half of the
      twentieth century. We describe here an extension of the concept of 1D fixed
      points to fixed lines in two dimensions. These structures become the fundamental
      entities for characterizing the nonlinear motion in the four-dimensional phase
      space (two degrees of freedom). 

PMID- 26196805
TI  - Experimental Evidence for Three Universality Classes for Reaction Fronts in
      Disordered Flows.
AB  - Self-sustained reaction fronts in a disordered medium subject to an external flow
      display self-affine roughening, pinning, and depinning transitions. We measure
      spatial and temporal fluctuations of the front in 1+1 dimensions, controlled by a
      single parameter, the mean flow velocity. Three distinct universality classes are
      observed, consistent with the Kardar-Parisi-Zhang (KPZ) class for fast advancing
      or receding fronts, the quenched KPZ class (positive-qKPZ) when the mean flow
      approximately cancels the reaction rate, and the negative-qKPZ class for slowly
      receding fronts. Both qKPZ classes exhibit distinct depinning transitions, in
      agreement with the theory. 

PMID- 26196807
TI  - Nonuniversality and Finite Dissipation in Decaying Magnetohydrodynamic
      Turbulence.
AB  - A model equation for the Reynolds number dependence of the dimensionless
      dissipation rate in freely decaying homogeneous magnetohydrodynamic turbulence in
      the absence of a mean magnetic field is derived from the real-space energy
      balance equation, leading to Cepsilon=Cepsilon,infinity+C/R-+O(1/R-(2)), where R-
      is a generalized Reynolds number. The constant Cepsilon,infinity describes the
      total energy transfer flux. This flux depends on magnetic and cross helicities,
      because these affect the nonlinear transfer of energy, suggesting that the value
      of Cepsilon,infinity is not universal. Direct numerical simulations were
      conducted on up to 2048(3) grid points, showing good agreement between data and
      the model. The model suggests that the magnitude of cosmological-scale magnetic
      fields is controlled by the values of the vector field correlations. The ideas
      introduced here can be used to derive similar model equations for other turbulent
      systems.

PMID- 26196808
TI  - Spectroscopic Determination of the Atomic f-Electron Symmetry Underlying Hidden
      Order in URu2Si2.
AB  - The low-temperature hidden-order state of URu2Si2 has long been a subject of
      intense speculation, and is thought to represent an as-yet-undetermined many-body
      quantum state not realized by other known materials. Here, x-ray absorption
      spectroscopy and high-resolution resonant inelastic x-ray scattering are used to
      observe electronic excitation spectra of URu2Si2, as a means to identify the
      degrees of freedom available to constitute the hidden-order wave function.
      Excitations are shown to have symmetries that derive from a correlated 5f(2)
      atomic multiplet basis that is modified by itinerancy. The features, amplitude,
      and temperature dependence of linear dichroism are in agreement with ground
      states that closely resemble the doublet Gamma5 crystal field state of uranium.

PMID- 26196809
TI  - Fluctuation Diagnostics of the Electron Self-Energy: Origin of the Pseudogap
      Physics.
AB  - We demonstrate how to identify which physical processes dominate the low-energy
      spectral functions of correlated electron systems. We obtain an unambiguous
      classification through an analysis of the equation of motion for the electron
      self-energy in its charge, spin, and particle-particle representations. Our
      procedure is then employed to clarify the controversial physics responsible for
      the appearance of the pseudogap in correlated systems. We illustrate our method
      by examining the attractive and repulsive Hubbard model in two dimensions. In the
      latter, spin fluctuations are identified as the origin of the pseudogap, and we
      also explain why d-wave pairing fluctuations play a marginal role in suppressing
      the low-energy spectral weight, independent of their actual strength. 

PMID- 26196810
TI  - Observation of a Devil's Staircase in the Novel Spin-Valve System SrCo6O11.
AB  - Using resonant soft-x-ray scattering as a function of both temperature and
      magnetic field, we reveal a large number of almost degenerate magnetic orders in
      SrCo6O11. The Ising-like spins in this frustrated material in fact exhibit a so
      called magnetic devil's staircase. It is demonstrated how a magnetic field
      induces transitions between different microscopic spin configurations, which is
      responsible for the magnetoresistance of SrCo6O11. This material therefore
      constitutes a unique combination of a magnetic devil's staircase and spin-valve
      effects, yielding a novel type of magnetoresistance system.

PMID- 26196811
TI  - Splitting of the Fermi Contour of Quasi-2D Electrons in Parallel Magnetic Fields.
AB  - In a quasi-two-dimensional electron system with nonzero layer thickness, a
      parallel magnetic field can couple to the out-of-plane electron motion and lead
      to a severe distortion and eventual splitting of the Fermi contour. Here we
      directly and quantitatively probe this evolution through commensurability and
      Shubnikov-de Haas measurements on electrons confined to a 40-nm-wide GaAs (001)
      quantum well. We are able to observe the Fermi contour splitting phenomenon, in
      good agreement with the results of semiclassical calculations. Experimentally, we
      also observe intriguing features, suggesting magnetic-breakdown-type behavior
      when the Fermi contour splits. 

PMID- 26196812
TI  - Electrical and Thermal Transport in Inhomogeneous Luttinger Liquids.
AB  - We study the transport properties of long quantum wires by generalizing the
      Luttinger liquid approach to allow for the finite lifetime of the bosonic
      excitations. Our theory accounts for long-range disorder and strong electron
      interactions, both of which are common features of experiments with quantum
      wires. We obtain the electrical and thermal resistances and thermoelectric
      properties of such quantum wires and find a strong deviation from perfect
      conductance quantization. We cast our results in terms of the thermal
      conductivity and bulk viscosity of the electron liquid and give the temperature
      scale above which the transport can be described by classical hydrodynamics. 

PMID- 26196813
TI  - Geometric Resonance of Composite Fermions Near the nu=1/2 Fractional Quantum Hall
      State.
AB  - We observe geometric resonance features of composite fermions on the flanks of
      the even-denominator nu=1/2 fractional quantum Hall state in high-mobility two
      dimensional electron and hole systems confined to wide GaAs quantum wells and
      subjected to a weak, strain-induced, unidirectional periodic potential
      modulation. The features provide a measure of how close to nu=1/2 the system
      stays single-component and supports a composite fermion Fermi sea before
      transitioning into a nu=1/2 fractional quantum Hall state, presumably, the two
      component Psi331 state.

PMID- 26196814
TI  - Remarkably Robust and Correlated Coherence and Antiferromagnetism in (Ce(1
      x)La(x))Cu2Ge2.
AB  - We present magnetic susceptibility, resistivity, specific heat, and
      thermoelectric power measurements on (Ce(1-x)La(x))Cu2Ge2 single crystals
      (0<=x<=1). With La substitution, the antiferromagnetic temperature TN is
      suppressed in an almost linear fashion and moves below 0.36 K, the base
      temperature of our measurements for x>0.8. Surprisingly, in addition to robust
      antiferromagnetism, the system also shows low temperature coherent scattering
      below Tcoh up to ~0.9 of La, indicating a small percolation limit ~9% of Ce. Tcoh
      as a function of magnetic field was found to have different behavior for x<0.9
      and x>0.9. Remarkably, (Tcoh)(2) at H=0 was found to be linearly proportional to
      TN. The jump in the magnetic specific heat deltaCm at TN as a function of TK/TN
      for (Ce(1-x)La(x))Cu2Ge2 follows the theoretical prediction based on the
      molecular field calculation for the S=1/2 resonant level model.

PMID- 26196815
TI  - Tunable Magnetism and Half-Metallicity in Hole-Doped Monolayer GaSe.
AB  - We find, through first-principles calculations, that hole doping induces a
      ferromagnetic phase transition in monolayer GaSe. Upon increasing hole density,
      the average spin magnetic moment per carrier increases and reaches a plateau near
      1.0 MUB per carrier in a range of 3*10(13)/cm(2)-1*10(14)/cm(2), with the system
      in a half-metal state before the moment starts to descend abruptly. The predicted
      itinerant magnetism originates from an exchange splitting of electronic states at
      the top of the valence band, where the density of states exhibits a sharp van
      Hove singularity in this quasi-two-dimensional system.

PMID- 26196816
TI  - Unified Picture for the Colossal Thermopower Compound FeSb2.
AB  - We identify the driving mechanism of the gigantic Seebeck coefficient in FeSb2 as
      the phonon-drag effect associated with an in-gap density of states that we
      demonstrate to derive from excess iron. We accurately model electronic and
      thermoelectric transport coefficients and explain the so far ill-understood
      correlation of maxima and inflection points in different response functions. Our
      scenario has far-reaching consequences for attempts to harvest the spectacular
      power factor of FeSb2.

PMID- 26196817
TI  - Pauli-Heisenberg Oscillations in Electron Quantum Transport.
AB  - We measure the current fluctuations emitted by a normal-metal-insulator-normal
      metal tunnel junction with a very wide bandwidth, from 0.3 to 13 GHz, down to
      very low temperature T=35  mK. This allows us to perform the spectroscopy (i.e.,
      measure the frequency dependence) of thermal noise (no dc bias, variable
      temperature) and shot noise (low temperature, variable dc voltage bias). Because
      of the very wide bandwidth of our measurement, we deduce the current-current
      correlator in the time domain. We observe the thermal decay of this correlator as
      well as its oscillations with a period h/eV, a direct consequence of the effect
      of the Pauli and Heisenberg principles in quantum electron transport. 

PMID- 26196818
TI  - Multiplasmon Absorption in Graphene.
AB  - We show that graphene possesses a strong nonlinear optical response in the form
      of multiplasmon absorption, with exciting implications in classical and quantum
      nonlinear optics. Specifically, we predict that graphene nanoribbons can be used
      as saturable absorbers with low saturation intensity in the far-infrared and
      terahertz spectrum. Moreover, we predict that two-plasmon absorption and extreme
      localization of plasmon fields in graphene nanodisks can lead to a plasmon
      blockade effect, in which a single quantized plasmon strongly suppresses the
      possibility of exciting a second plasmon. 

PMID- 26196820
TI  - Topological Superconductivity and High Chern Numbers in 2D Ferromagnetic Shiba
      Lattices.
AB  - Inspired by the recent experimental observation of topological superconductivity
      in ferromagnetic chains, we consider a dilute 2D lattice of magnetic atoms
      deposited on top of a superconducting surface with a Rashba spin-orbit coupling.
      We show that the studied system supports a generalization of px+ipy
      superconductivity and that its topological phase diagram contains Chern numbers
      higher than xi/a(?1), where xi is the superconducting coherence length and a is
      the distance between the magnetic atoms. The signatures of nontrivial topology
      can be observed by STM spectroscopy in finite-size islands.

PMID- 26196819
TI  - Position-Momentum Duality and Fractional Quantum Hall Effect in Chern Insulators.
AB  - We develop a first quantization description of fractional Chern insulators that
      is the dual of the conventional fractional quantum Hall (FQH) problem, with the
      roles of position and momentum interchanged. In this picture, FQH states are
      described by anisotropic FQH liquids forming in momentum-space Landau levels in a
      fluctuating magnetic field. The fundamental quantum geometry of the problem
      emerges from the interplay of single-body and interaction metrics, both of which
      act as momentum-space duals of the geometrical picture of the anisotropic FQH
      effect. We then present a novel broad class of ideal Chern insulator lattice
      models that act as duals of the isotropic FQH effect. The interacting problem is
      well-captured by Haldane pseudopotentials and affords a detailed microscopic
      understanding of the interplay of interactions and nontrivial quantum geometry. 

PMID- 26196822
TI  - Spin Chirality Tuning and Topological Semimetals in Strained HgTe(x)S(1-x).
AB  - By means of detailed electronic structure calculations, we show that strained
      HgTe(x)S(1-x) alloys show a surprisingly rich topological phase diagram. In the
      strong topological insulator phase, the spin chirality of the topological
      nontrivial surface states can be reversed by adjusting the alloy concentration x
      and the strain. On top of this, we predict two semimetallic topological phases,
      namely, a Dirac semimetal and a Weyl semimetal. The topological phases are
      characterized by their Z2 invariants and their mirror Chern numbers.

PMID- 26196821
TI  - Impurity-Induced Bound States in Superconductors with Spin-Orbit Coupling.
AB  - We study the effect of strong spin-orbit coupling (SOC) on bound states induced
      by impurities in superconductors. The presence of SOC breaks the SU(2)-spin
      symmetry and causes the superconducting order parameter to have generically both
      singlet (s-wave) and triplet (p-wave) components. We find that in the presence of
      SOC the spectrum of Yu-Shiba-Rusinov (YSR) states is qualitatively different in s
      wave and p-wave superconductors, a fact that can be used to identify the
      superconducting pairing symmetry of the host system. We also predict that, in the
      presence of SOC, the spectrum of the impurity-induced bound states depends on the
      orientation of the magnetic moment S of the impurity and, in particular, that by
      changing the orientation of S, the fermion-parity of the lowest energy bound
      state can be tuned. We then study the case of a dimer of magnetic impurities and
      show that, in this case, the YSR spectrum for a p-wave superconductor is
      qualitatively very different from the one for an s-wave superconductor even in
      the limit of vanishing SOC. 

PMID- 26196823
TI  - Emergent Spacetime Supersymmetry in 3D Weyl Semimetals and 2D Dirac Semimetals.
AB  - Supersymmetry (SUSY) interchanges bosons and fermions but no direct evidence of
      it has been revealed in nature yet. In this Letter, we observe that fluctuating
      pair density waves (PDW) consist of two complex order parameters which can be
      superpartners of the unavoidably doubled Weyl fermions in three-dimensional
      lattice models. We construct explicit fermionic lattice models featuring 3D Weyl
      fermions and show that PDW is the leading instability via a continuous phase
      transition as short-range interactions exceed a critical value. Using a
      renormalization group, we theoretically show that N=2 space-time SUSY emerges at
      the continuous PDW transitions in 3D Weyl semimetals, which we believe is the
      first realization of emergent (3+1)D space-time SUSY in microscopic lattice
      models. We further discuss possible routes to realize such lattice models and
      experimental signatures of emergent SUSY at the PDW criticality. 

PMID- 26196824
TI  - Frequency-Independent Response of Self-Complementary Checkerboard Screens.
AB  - This research resolves a long-standing problem on the electromagnetic response of
      self-complementary metallic screens with checkerboardlike geometry. Although
      Babinet's principle implies that they show a frequency-independent response, this
      unusual characteristic has not been observed yet due to the singularities of the
      metallic point contacts in the checkerboard geometry. We overcome this difficulty
      by replacing the point contacts with resistive sheets. The proposed structure is
      prepared and characterized by terahertz time-domain spectroscopy. It is
      experimentally confirmed that the resistive checkerboard structures exhibit a
      flat transmission spectrum over 0.1-1.1 THz. It is also demonstrated that self
      complementarity can eliminate even the frequency-dependent transmission
      characteristics of resonant metamaterials. 

PMID- 26196825
TI  - Hyperbolic Metamaterials with Bragg Polaritons.
AB  - We propose a novel mechanism for designing quantum hyperbolic metamaterials with
      the use of semiconductor Bragg mirrors containing periodically arranged quantum
      wells. The hyperbolic dispersion of exciton-polariton modes is realized near the
      top of the first allowed photonic miniband in such a structure which leads to the
      formation of exciton-polariton X waves. Exciton-light coupling provides a
      resonant nonlinearity which leads to nontrivial topologic solutions. We predict
      the formation of low amplitude spatially localized oscillatory structures:
      oscillons described by kink shaped solutions of the effective Ginzburg-Landau
      Higgs equation. The oscillons have direct analogies in gravitational theory. We
      discuss implementation of exciton-polariton Higgs fields for the Schrodinger cat
      state generation. 

PMID- 26196826
TI  - Optical Realization of Double-Continuum Fano Interference and Coherent Control in
      Plasmonic Metasurfaces.
AB  - Classical realization of a ubiquitous quantum mechanical phenomenon of double
      continuum Fano interference using metasurfaces is experimentally demonstrated by
      engineering the near-field interaction between two bright and one dark plasmonic
      modes. The competition between the bright modes, one of them effectively
      suppressing the Fano interference for the orthogonal light polarization, is
      discovered. Coherent control of optical energy concentration and light absorption
      by the ellipticity of the incident light is theoretically predicted. 

PMID- 26196827
TI  - Fermi Surface of Three-Dimensional La(1-x)Sr(x)MnO3 Explored by Soft-X-Ray ARPES:
      Rhombohedral Lattice Distortion and its Effect on Magnetoresistance.
AB  - Electronic structure of the three-dimensional colossal magnetoresistive
      perovskite La(1-x)Sr(x)MnO3 has been established using soft-x-ray angle-resolved
      photoemission spectroscopy with its intrinsically sharp definition of three
      dimensional electron momentum. The experimental results show much weaker
      polaronic coupling compared to the bilayer manganites and are consistent with the
      theoretical band structure including the empirical Hubbard parameter U. The
      experimental Fermi surface unveils the canonical topology of alternating three
      dimensional electron spheres and hole cubes, with their shadow contours
      manifesting the rhombohedral lattice distortion. This picture has been confirmed
      by one-step photoemission calculations including displacement of the apical
      oxygen atoms. The rhombohedral distortion is neutral to the Jahn-Teller effect
      and thus polaronic coupling, but affects the double-exchange electron hopping and
      thus the colossal magnetoresistance effect.

PMID- 26196828
TI  - Porous Liquid Phases for Indented Colloids with Depletion Interactions.
AB  - We study indented spherical colloids, interacting via depletion forces. These
      systems exhibit liquid-vapor phase transitions whose properties are determined by
      a combination of strong "lock-and-key" bonds and weaker nonspecific interactions.
      As the propensity for lock-and-key binding increases, the critical point moves to
      significantly lower density, and the coexisting phases change their structure. In
      particular, the liquid phase is porous, exhibiting large percolating voids. The
      properties of this system depend strongly on the topological structure of an
      underlying bond network: we comment on the implications of this fact for the
      assembly of equilibrium states with controlled porous structures. 

PMID- 26196829
TI  - Underlying Asymmetry within Particle Size Segregation.
AB  - We experimentally study particle scale dynamics during segregation of a
      bidisperse mixture under oscillatory shear. Large and small particles show an
      underlying asymmetry that is dependent on the local particle concentration, with
      small particles segregating faster in regions of many large particles and large
      particles segregating slower in regions of many small particles. We quantify the
      asymmetry on bulk and particle scales, and capture it theoretically. This gives
      new physical insight into segregation and reveals a similarity with
      sedimentation, traffic flow, and particle diffusion. 

PMID- 26196830
TI  - Disentangling the Free-Fall Arch Paradox in Silo Discharge.
AB  - Several theoretical predictions of the mass flow rate of granular media
      discharged from a silo are based on the spontaneous development of a free-fall
      arch region, the existence of which is still controversial. In this Letter, we
      study experimentally and numerically the particle flow through an orifice placed
      at the bottom of 2D and 3D silos. The implementation of a coarse-grained
      technique allows a thorough description of all the kinetic and micromechanical
      properties of the particle flow in the outlet proximities. Though the free-fall
      arch does not exist as traditionally understood--a region above which particles
      have negligible velocity and below which particles fall solely under gravity
      action--we discover that the kinetic pressure displays a well-defined transition
      in a position that scales with the outlet size. This universal scaling explains
      why the free-fall arch picture has served as an approximation to describe the
      flow rate in the discharge of silos.

PMID- 26196831
TI  - Statistical Physics Methods Provide the Exact Solution to a Long-Standing Problem
      of Genetics.
AB  - Analytic and computational methods developed within statistical physics have
      found applications in numerous disciplines. In this Letter, we use such methods
      to solve a long-standing problem in statistical genetics. The problem, posed by
      Haldane and Waddington [Genetics 16, 357 (1931)], concerns so-called recombinant
      inbred lines (RILs) produced by repeated inbreeding. Haldane and Waddington
      derived the probabilities of RILs when considering two and three genes but the
      case of four or more genes has remained elusive. Our solution uses two
      probabilistic frameworks relatively unknown outside of physics: Glauber's formula
      and self-consistent equations of the Schwinger-Dyson type. Surprisingly, this
      combination of statistical formalisms unveils the exact probabilities of RILs for
      any number of genes. Extensions of the framework may have applications in
      population genetics and beyond. 

PMID- 26196832
TI  - Antipolar and Anticlinic Mesophase Order in Chromatin Induced by Nucleosome
      Polarity and Chirality Correlations.
AB  - Contrary to the usual "rigid supermolecular assembly" paradigm of chromatin
      structure, we propose to analyze its eventual ordered state in terms of symmetry
      properties of individual nucleosomes that give rise to mesophase order
      parameters, like in many other soft-matter systems. Basing our approach on the
      Landau-de Gennes phenomenology, we describe the mesoscale order in chromatin by
      antipolar and anticlinic correlations of chiral individual nucleosomes. This
      approach leads to a unifying physical picture of a whole series of soft locally
      ordered states with different apparent structures, including the recently
      observed heteromorphic chromatin, stemming from the antipolar arrangement of
      nucleosomes complemented by their chiral twisting. Properties of these states
      under an external force field can reconcile apparently contradictory results of
      single-molecule experiments. 

PMID- 26196833
TI  - Programed Death is Favored by Natural Selection in Spatial Systems.
AB  - Standard evolutionary theories of aging and mortality, implicitly based on mean
      field assumptions, hold that programed mortality is untenable, as it opposes
      direct individual benefit. We show that in spatial models with local
      reproduction, programed deaths instead robustly result in long-term benefit to a
      lineage, by reducing local environmental resource depletion via spatiotemporal
      patterns causing feedback over many generations. Results are robust to model
      variations, implying that direct selection for shorter life span may be quite
      widespread in nature. 

PMID- 26196834
TI  - Log-Log Convexity of Type-Token Growth in Zipf's Systems.
AB  - It is traditionally assumed that Zipf's law implies the power-law growth of the
      number of different elements with the total number of elements in a system-the so
      called Heaps' law. We show that a careful definition of Zipf's law leads to the
      violation of Heaps' law in random systems, with growth curves that have a convex
      shape in log-log scale. These curves fulfill universal data collapse that only
      depends on the value of Zipf's exponent. We observe that real books behave very
      much in the same way as random systems, despite the presence of burstiness in
      word occurrence. We advance an explanation for this unexpected correspondence. 

PMID- 26196835
TI  - Environmental DNA COI barcoding for quantitative analysis of protists
      communities: A test using the Nebela collaris complex (Amoebozoa; Arcellinida;
      Hyalospheniidae).
AB  - Environmental DNA surveys are used for screening eukaryotic diversity. However,
      it is unclear how quantitative this approach is and to what extent results from
      environmental DNA studies can be used for ecological studies requiring
      quantitative data. Mitochondrial cytochrome oxidase (COI) is used for species
      level taxonomic studies of testate amoebae and should allow assessing the
      community composition from environmental samples, thus bypassing biases due to
      morphological identification. We tested this using a COI clone library approach
      and focusing on the Nebela collaris complex. Comparisons with direct microscopy
      counts showed that the COI clone library diversity data matched the
      morphologically identified taxa, and that community composition estimates using
      the two approaches were similar. However, this correlation was improved when
      microscopy counts were corrected for biovolume. Higher correlation with biovolume
      corrected community data suggests that COI clone library data matches the ratio
      of mitochondria and that within closely-related taxa the density of mitochondria
      per unit biovolume is approximately constant. Further developments of this
      metabarcoding approach including quantifying the mitochondrial density among
      closely-related taxa, experiments on other taxonomic groups and using high
      throughput sequencing should make if possible to quantitatively estimate
      community composition of different groups, which would be invaluable for
      microbial food webs studies. 

PMID- 26196836
TI  - Lung Ischemia-Reperfusion is a Sterile Inflammatory Process Influenced by
      Commensal Microbiota in Mice.
AB  - Lung ischemia-reperfusion (IR) complicates numerous clinical processes, such as
      cardiac arrest, transplantation, and major trauma. These conditions generate
      sterile inflammation, which can cause or worsen acute lung injury. We previously
      reported that lung and systemic inflammation in a mouse model of ventilated lung
      IR depends on Toll-like receptor 4 (TLR-4) signaling and the presence of alveolar
      macrophages. Here, we tested the hypothesis that the intestinal microbiome has a
      role in influencing the inflammatory response to lung IR. Lung IR was created in
      intubated mechanically ventilated mice via reversible left pulmonary artery
      occlusion followed by reperfusion. Inflammatory markers and histology were
      tracked during varying periods of reperfusion (from 1 to 24 h). Separate groups
      of mice were given intestinally localized antibiotics for 8 to 10 weeks and then
      were subjected to left lung IR and analysis of lungs and plasma for markers of
      inflammation. Alveolar macrophages from antibiotic-treated or control mice were
      tested ex vivo for inflammatory responses to bacterial TLR agonists, namely,
      lipopolysaccharide and Pam3Cys. We found that inflammation generated by left lung
      IR was rapid in onset and dissipated within 12 to 24 h. Treatment of mice with
      intestinally localized antibiotics was associated with a marked attenuation of
      circulating and lung inflammatory markers as well as reduced histologic evidence
      of infiltrating cells and edema in the lung after IR. Alveolar macrophages from
      antibiotic-treated mice produced less cytokines ex vivo when stimulated with TLR
      agonists as compared with those from control mice. Our data indicate that the
      inflammatory response induced by nonhypoxic lung IR is transient and is strongly
      influenced by intestinal microbiota. Furthermore, these data suggest that the
      intestinal microbiome could potentially be manipulated to attenuate the post-IR
      pulmonary inflammatory response. 

PMID- 26196837
TI  - TEMPORAL LINKS BETWEEN ENDOTOXIN ACTIVITY LEVELS AND INTERLEUKIN 6 CONCENTRATIONS
      IN ABDOMINAL SEPSIS.
AB  - In severe human peritonitis, the precise pathophysiological importance of
      endotoxin is controversial. Prognostic and therapeutic studies have yielded
      conflicting results. The current study wanted to investigate qualitative,
      quantitative, and temporal associations between blood endotoxin activity (EA)
      levels and acute inflammatory reactions. We conducted a prospective observational
      study in 30 patients with intra-abdominal infections who had undergone specific
      focus therapies (surgical/radiological/pharmaceutical interventions) and who
      required intensive care therapy. We performed sequential postinterventional
      measurements of blood EA levels and plasma interleukin 6 (IL-6) concentrations
      until recurrence or cure. There was no association between daily EA levels and IL
      6 concentrations, or daily EA levels and changes in IL-6 concentrations on
      subsequent days. We found, however, a significant association between EA levels
      and IL-6 concentrations, when newly changing EA levels were referred to
      subsequent changes in IL-6 concentrations (P < 0.05). Increasing EA levels were
      followed by a 90% increase of subsequent IL-6 concentrations during the next 24
      to 48 h, whereas decreasing/stable EA levels were associated with slightly
      decreasing IL-6 concentrations (P < 0.05). Our findings suggest an altered
      response of the innate immune system because postinterventional EA levels did not
      vary with concomitant or subsequent inflammatory reactions and because
      inflammatory responses to newly increasing EA levels were delayed and
      comparatively small. Still, our results support the concept that endotoxin is a
      trigger of inflammatory reactions in human peritonitis. 

PMID- 26196838
TI  - EFFECTS OF EXPERIMENTAL HUMAN ENDOTOXEMIA ON DIAPHRAGM FUNCTION.
AB  - INTRODUCTION: Systemic inflammation is a well-known risk factor for respiratory
      muscle weakness. Studies using animal models of inflammation have shown that
      endotoxin administration induces diaphragm dysfunction. However, the effects of
      in vivo endotoxin administration on diaphragm function in humans have not been
      studied. Our aim was to evaluate diaphragm function in a model of systemic
      inflammation in healthy subjects. METHODS: Two groups of 12 male volunteers
      received an intravenous bolus of 2 ng/kg of Escherichia coli lipopolysaccharide
      (LPS) and were monitored until 8 h after LPS administration. In the first group,
      the twitch transdiaphragmatic pressure (Pditw) and compound muscle action
      potential of the diaphragm (CMAPdi) were measured. In addition, plasma levels of
      cytokines, heart rate, and arterial blood pressure were measured. In the second
      group, catecholamines as well as respiratory rate and blood gas values were
      measured. Diaphragm ultrasonography was performed in four subjects with severe
      shivering. RESULTS: Lipopolysaccharide administration resulted in flulike
      symptoms, hemodynamic alterations, and increased plasma levels of cytokines. The
      Pditw increased after LPS administration from 31.2 +/- 2.0 cmH2O (baseline) to
      38.8 +/- 2.0 cmH2O (t = 1 h) and 35.4 +/- 2.0 cmH2O (t = 1.5 h). There was no
      correlation between cytokine plasma levels and the Pditw. We found a trend toward
      a gradual decrease in the CMAPdi from 0.78 +/- 0.07 mV (baseline) to 0.58 +/-
      0.05 mV (t = 2 h). Respiratory rate increased after LPS administration from 16.8
      +/- 0.5 breaths/min (baseline) to 20.3 +/- 0.6 breaths/min (t = 4 h), with a
      resulting decrease in PaCO2 of 0.5 +/- 0.1 kPa. Plasma levels of epinephrine
      peaked at t = 1.5 h, with an increase of 1.3 +/- 0.3 nmol/L from baseline. Rapid
      diaphragm contractions consistent with shivering were observed. CONCLUSIONS: This
      study shows that, in contrast to diaphragm dysfunction observed in animal models
      of inflammation, in vivo diaphragm contractility is augmented in the early phase
      after low-dose endotoxin administration in humans.

PMID- 26196839
TI  - CT-proAVP IS NOT A GOOD PREDICTOR OF VASOPRESSOR NEED IN SEPTIC SHOCK.
AB  - INTRODUCTION: Septic shock features a high hospital mortality. Improving our
      ability to risk stratify these patients at admission may help better define
      management strategies and design studies. The primary objective of this study was
      to determine if patients dead or with sustained vasopressor need at day 7 had a
      relative arginine vasopressin (AVP) deficiency as compared with vasopressor-free
      patients at day 7. Another objective was to explore if plasma CT-proAVP (C
      terminal part of preprovasopressin) measured within 24 h of sepsis onset could
      predict patient severity. METHODS: This was a prospective observational study in
      a medical and surgical intensive care unit. One hundred thirteen patients were
      included in this analysis: 102 patients with severe sepsis or septic shock and 11
      nonseptic controls. The CT-proAVP was measured at three time points within the
      first week after sepsis onset. RESULTS: The CT-proAVP measured within 24 h of
      sepsis onset failed to predict vasopressor need. More importantly, CT-proAVP
      plasma levels in patients with a sustained need of vasopressors did not differ
      from vasopressor-free patients at days 1 and 2. The CT-proAVP was more elevated
      in septic shock as compared with severe sepsis or nonseptic patients. When
      analyzing 28-day mortality, nonsurvivors featured higher levels of the CT-proAVP
      compared with survivors. CONCLUSIONS: Patients with septic shock and sustained
      need of vasopressors do not seem to present a relative AVP deficiency. In sepsis,
      the subgroup of patients that may benefit from AVP supplementation still needs to
      be identified. Our study further confirms previous data on the ability of the CT
      proAVP to predict patient severity in severe sepsis and septic shock.

PMID- 26196840
TI  - A "CLEAN CASE" OF SYSTEMIC INJURY: MESENTERIC LYMPH AFTER HEMORRHAGIC SHOCK
      ELICITS A STERILE INFLAMMATORY RESPONSE.
AB  - Postinjury multiple organ failure results from an inappropriate overwhelming
      immune response to injury. During trauma and hemorrhagic shock (T/HS), mesenteric
      ischemia causes gut mucosal breakdown with disruption of the intestinal barrier.
      It has been proposed that this releases the gut microbiota systemically via
      postshock mesenteric lymph (PSML), engendering infectious complications. Despite
      extensive investigation, no clear evidence has been presented for gut bacterial
      translocation after resuscitation from T/HS. However, such previous studies were
      limited by available technologies. More sensitive methods, such as quantitative
      polymerase chain reaction, have since emerged for detection of bacterial presence
      and danger-associated molecular patterns (DAMPs). Quantitative polymerase chain
      reaction was applied to PSML derived from a rat model of T/HS. No bacterial
      presence was detected in a series of 12 samples, whereas multiple lymph samples
      showed the presence of DAMPs after T/HS. Thus, we confirmed that bacterial
      translocation does not exist in PSML after resuscitation from T/HS-associated
      mesenteric ischemia. However, T/HS does increase the presence of mitochondrial
      DAMPs in PSML. These results support our current position that PSML elaborates
      remote organ injury by multiple inflammatory mechanisms, including lipid-mediated
      proinflammatory stimuli, and by contribution from gut-derived DAMPs. 

PMID- 26196841
TI  - Central Venous Pressure Dropped Early is Associated with Organ Function and
      Prognosis in Septic Shock Patients: A Retrospective Observational Study.
AB  - PURPOSE: The aim of this study was to investigate changes in central venous
      pressure (CVP) of patients with septic shock over 7 days after intensive care
      unit admission and its effect on organ function and clinical prognosis. METHODS:
      Baseline data, 7 days' CVP, and laboratory data of 105 patients with septic shock
      were consecutively recorded. According to the value of mean CVP of 7 days, cases
      were divided into three groups: low (<8 mmHg), normal (8-12 mmHg), and high (>12
      mmHg) CVP. According to whether CVP dropped to less than 8 mmHg, cases were
      divided into two groups. RESULTS: There were significant differences in serum
      creatinine on day 5 and lactate on days 2 to 5 among low, normal, and high-CVP
      groups (P < 0.05). Total bilirubin on days 5 to 7, lactate on days 2 and 4 to 7,
      and SOFA (Sepsis-related Organ Failure Assessment) scores on days 5 and 7 in
      groups with CVP did not drop to less than 8 mmHg were higher than those in groups
      with CVP that dropped to less than 8 mmHg (P < 0.05). PO2/FIO2 on day 7 was lower
      in the group whose CVP did not drop to less than 8 mmHg (226 [184-278]) vs. 254
      [214-306]; P = 0.048), whereas 28-day mortality was lower in the group whose CVP
      dropped to less than 8 mmHg (18.3% vs. 37.8%, P = 0.026). CONCLUSIONS: Central
      venous pressure was associated with kidney, liver, and lung function; SOFA
      scores; and lactate. Septic shock patients whose CVP dropped to less than 8 mmHg
      during 7 days had a higher survival rate.

PMID- 26196842
TI  - Skeletal Muscle Loss is Associated with TNF Mediated Insufficient Skeletal
      Myogenic Activation After Burn.
AB  - Muscle loss accompanies severe burn; in this hyper-catabolic state, muscle
      undergoes atrophy through protein degradation and disuse. Muscle volume is
      related to the relative rates of cellular degradation and myogenesis. We
      hypothesize that muscle atrophy after injury is in part because of insufficient
      myogenesis associated with the hyper-inflammatory response. The aim of this study
      was to investigate the role of skeletal myogenesis and muscle cell homeostasis in
      response to severe burn. Twenty-eight male C57BL6 mice received 25% TBSA scald.
      Gluteus muscle from these animals was analyzed at days 1, 3, 7, and 14 after
      injury. Six additional animals without burn served as controls. We showed muscle
      wet weight and protein content decreased at days 3 and 7 after burn, with
      elevated tumor necrosis factor (TNF) mRNA expression (P < 0.05). Increased cell
      death was observed through TUNEL staining, and cleaved caspase-3 levels reached a
      peak in muscle lysate at day 3 (P < 0.05). The cell proliferation marker
      proliferating cell nuclear antigen (PCNA) significantly increased after burn,
      associated with increased gene and protein expression of myogenesis markers Pax7
      and myogenin. Desmin mRNA expression and the ratio of desmin to PCNA protein
      expression, however, significantly decreased at day 7 (P < 0.05). In vitro, the
      ratio of desmin to PCNA protein expression significantly decreased in C2C12
      murine myoblasts after TNF-alpha stimulation for 24 h. We showed that severe burn
      induces both increased cell death and proliferation. Myogenesis, however, does
      not counterbalance increased cell death after burn. Data suggest insufficient
      myogenesis might be associated with pro-inflammatory mediator TNF activity. 

PMID- 26196843
TI  - Maresin 1 Inhibits Epithelial-to-Mesenchymal Transition in Vitro and Attenuates
      Bleomycin Induced Lung Fibrosis in Vivo.
AB  - Lung fibrosis is an aggressive disease with uncontrolled fibrotic response and no
      effective therapeutic treatment. Epithelial-to-mesenchymal transition (EMT) has
      been proved to be an important pathological feature in lung fibrosis. In this
      study, we investigated whether MaR1, a kind of proresolving lipid mediators,
      could inhibit TGF-beta1-induced EMT in vitro and lung fibrosis in vivo. In vitro
      study, mouse type II alveolar epithelial cells were treated with different does
      of MaR1 for 30 min and were exposed to TGF-beta1 for 48 h. In vivo study, C57BL/6
      mice were administered bleomycin intratracheally. After 14 days, MaR1 was
      injected intraperitoneally daily for 7 days. In day 28, mice were sacrificed. The
      results demonstrate that treatment of mouse type II alveolar epithelial cells
      with MaR1 (10 nM) significantly prevents TGF-beta1-induced fibronectin and alpha
      SMA expression and restores E-Cadherin level. The down-regulation of profibrotic
      molecules of MaR1 is associated with suppression of Smad2/3 and Akt
      phosphorylation. In vivo, MaR1 treatment significantly prolongs survival rate and
      attenuates destruction of lung architecture, as well as collagen deposition after
      bleomycin inhalation. TGF-beta1 concentration in bronchoalveolar lavage and
      fibrotic markers (fibronectin and alpha-SMA) in lung tissues are inhibited by
      MaR1 administration. These data indicate that MaR1 inhibits TGF-beta1-induced EMT
      and attenuates bleomycin-induced pulmonary fibrosis. MaR1 may be a promising
      strategy for alleviation of lung fibrosis.

PMID- 26196844
TI  - MARESIN 1 PREVENTS LIPOPOLYSACCHARIDE-INDUCED NEUTROPHIL SURVIVAL AND ACCELERATES
      RESOLUTION OF ACUTE LUNG INJURY.
AB  - Acute lung injury (ALI) is characterized by lung inflammation and diffuse
      infiltration of neutrophils. Neutrophil apoptosis is recognized as an important
      control point in the resolution of inflammation. Maresin 1 (MaR1) is a new
      docosahexaenoic acid-derived proresolving agent that promotes the resolution of
      inflammation. However, its function in neutrophil apoptosis is unknown. In this
      study, isolated human neutrophils were incubated with MaR1, the pan-caspase
      inhibitor z-VAD-fmk, and lipopolysaccharide (LPS) to determine the mechanism of
      neutrophil apoptosis. Acute lung injury was induced by intratracheal instillation
      of LPS. In addition, mice were treated with MaR1 intravenously at the peak of
      inflammation and administered z-VAD-fmk intraperitoneally. We found that culture
      of isolated human neutrophils with LPS dramatically delayed neutrophil apoptosis
      through the phosphorylation of AKT, ERK, and p38 to upregulate the expression of
      the antiapoptotic proteins Mcl-1 and Bcl-2, which was blocked by pretreatment
      with MaR1 in vitro. In mice, MaR1 accelerated the resolution of inflammation in
      LPS-induced ALI through attenuation of neutrophil accumulation, pathohistological
      changes, and pulmonary edema. Maresin 1 promoted resolution of inflammation by
      accelerating caspase-dependent neutrophil apoptosis. Moreover, MaR1 also reduced
      the LPS-induced production of proinflammatory cytokines and upregulated the
      production of the anti-inflammatory cytokine interleukin-10. In contrast,
      treatment with z-VAD-fmk inhibited the proapoptotic action of MaR1 and attenuated
      the protective effects of MaR1 in LPS-induced ALI. Taken together, MaR1 promotes
      the resolution of LPS-induced ALI by overcoming LPS-mediated suppression of
      neutrophil apoptosis. 

PMID- 26196845
TI  - Enterocyte Damage: A Piece in the Puzzle of Post-Cardiac Arrest Syndrome.
AB  - Cardiac arrest is considered to be a cause of small bowel ischemia, but the
      consequences of cardiac arrest on the human small bowel have been rarely studied.
      Plasma citrulline concentration is a marker of functional enterocyte mass, and
      plasma intestinal fatty acid-binding protein (I-FABP) concentration is a marker
      of enterocyte damage. We aimed to measure enterocyte biomarkers after cardiac
      arrest and to study the prognostic value of biomarker abnormalities. This is a
      prospective, observational, single-center study of patients admitted to the
      intensive care unit (ICU) for cardiac arrest, evaluating plasma citrulline and I
      FABP concentrations at admission and after 24  h and variables according to the
      Utstein criteria. Variables according to 28-day Cerebral Performance Category
      score of 1 to 2 (good neurological outcome) versus 3 to 5 (poor neurological
      outcome) were compared. Sixty-nine patients with cardiac arrest of both cardiac
      and hypoxic origin were included. At ICU admission, plasma citrulline
      concentration was low in 65% and plasma I-FABP was elevated in 82% of the
      patients. After 24  h, plasma citrulline was low in 82% and I-FABP was normal in
      60% of the patients. Patients with a poor neurological outcome had a lower plasma
      citrulline concentration and a higher I-FABP concentration at ICU admission. By
      multivariate analysis, plasma citrulline levels of 13.1  MUmol L or less and I
      FABP more than 260  pg mL were independently associated with a poor neurological
      outcome (odds ratio, 21.9 [2.2-215], and odds ratio, 13.6 [1.4-129],
      respectively). Cardiac arrest resuscitation is associated with evidence of small
      bowel mucosal damage in most patients, with a short and intense I-FABP elevation
      at admission and a decrease in citrulline concentration during the first day. In
      this study, low plasma citrulline and high I-FABP concentrations at ICU admission
      were predictive of a poor neurological outcome. This study confirms that cardiac
      arrest is a model of small bowel mucosal ischemia and suggests that enterocyte
      damage is a piece in the puzzle of post-cardiac arrest syndrome.

PMID- 26196846
TI  - Serum S100beta Neuroprotein Reduces Use of Cranial Computed Tomography in
      Children After Minor Head Trauma.
AB  - Minor head trauma is a common reason for consultation in pediatric emergency
      departments. In 2009, the Pediatric Emergency Care Applied Research Network
      (PECARN) published a clinical decision rule for its management. It aimed to help
      clinicians identify children with a very low risk of developing intracranial
      lesions, so that unnecessary cranial computed tomography (CCT) scan radiation
      could be avoided, as such exposure is associated with a rising risk of cancer in
      this young population. In the meantime, the serum S100beta neuroprotein showed
      encouraging results, with a 30% potential decrease in CCTs for the management of
      minor head traumas in adults and children. The aim of this study was to determine
      if the serum S100beta neuroprotein, associated with the PECARN clinical decision
      rule, could safely reduce the use of CCTs. We included children who were examined
      at the pediatric emergency department for minor head trauma, who underwent a CCT,
      whose blood samples were analyzed to determine the level of the serum S100beta
      protein. They were managed according to the PECARN clinical decision rule. We
      afterward assessed the potential decrease in the number of CCTs, according to a
      modified PECARN clinicobiological decision rule, had we taken into account the
      result of the blood tests. One hundred nine children were included, and nine of
      them had clinically important traumatic brain injury. Four of them had a negative
      S100beta value but were classified as high risk of developing intracranial lesion
      according to the PECARN clinical decision rule. Had we taken into account the
      modified PECARN clinicobiological decision rule, none of them would have been
      missed. However, there were 32 true negatives of the rule, allowing a potential
      decrease in CCTs rated at 29% (95% confidence interval, 21-38). Integrating the
      serum S100beta neuroprotein assessment in the PECARN clinical decision rule could
      avoid deleterious exposure to CCT radiation, with the condition of using a
      clinicobiological rule to avoid missing clinically important traumatic brain
      injuries. Those results have yet to be confirmed relying on a large multicentric
      study. 

PMID- 26196848
TI  - Asymmetric Papilledema in Idiopathic Intracranial Hypertension: Comment.

PMID- 26196847
TI  - Dual Raman-Brillouin Microscope for Chemical and Mechanical Characterization and
      Imaging.
AB  - We present a unique confocal microscope capable of measuring the Raman and
      Brillouin spectra simultaneously from a single spatial location. Raman and
      Brillouin scattering offer complementary information about a material's chemical
      and mechanical structure, respectively, and concurrent monitoring of both of
      these spectra would set a new standard for material characterization. We achieve
      this by applying recent innovations in Brillouin spectroscopy that reduce the
      necessary acquisition times to durations comparable to conventional Raman
      spectroscopy while attaining a high level of spectral accuracy. To demonstrate
      the potential of the system, we map the Raman and Brillouin spectra of a molded
      poly(ethylene glycol) diacrylate (PEGDA) hydrogel sample in cyclohexane to create
      two-dimensional images with high contrast at microscale resolutions. This
      powerful tool has the potential for very diverse analytical applications in basic
      science, industry, and medicine. 

PMID- 26196849
TI  - New directions in the science and technology of advanced sheet explosive
      formulations and the key energetic materials used in the processing of sheet
      explosives: Emerging trends.
AB  - This review presents the work carried out by the international community in the
      area of sheet explosive formulations and its applications in various systems. The
      sheet explosive is also named as PBXs and is a composite material in which solid
      explosive particles like RDX, HMX or PETN are dispersed in a polymeric matrix,
      forms a flexible material that can be rolled/cut into sheet form which can be
      applied to any complex contour. The designed sheet explosive must possess
      characteristic properties such as flexible, cuttable, water proof, easily
      initiable, and safe handling. The sheet explosives are being used for protecting
      tanks (ERA), light combat vehicle and futuristic infantry carrier vehicle from
      different attacking war heads etc. Besides, sheet explosives find wide
      applications in demolition of bridges, ships, cutting and metal cladding. This
      review also covers the aspects such as risks and hazard analysis during the
      processing of sheet explosive formulations, effect of ageing on sheet explosives,
      detection and analysis of sheet explosive ingredients and the R&D efforts of
      Indian researchers in the development of sheet explosive formulations. To the
      best of our knowledge, there has been no review article published in the
      literature in the area of sheet explosives. 

PMID- 26196850
TI  - Ascertainment of Testosterone Prescribing Practices in the VA.
AB  - BACKGROUND: Prescribing of exogenous testosterone is increasing. Because of the
      risks associated with testosterone, it is important to follow evidence-based
      procedures when initiating therapy. OBJECTIVE: We evaluated whether dispensing of
      testosterone was preceded by appropriate ascertainment of androgen deficiency,
      and consideration of potential contraindications, in accordance with practice
      guidelines. RESEARCH DESIGN: A cross-sectional study. SETTING: All outpatient
      clinics within Veterans Affairs (VA) during fiscal years 2009-2012 (FY09-FY12).
      SUBJECTS: A total of 111,631 men who had not previously received testosterone
      from VA, and received at least 1 testosterone dispensing during the study period.
      A 1-year "look-back" period was used to check for diagnostic tests that occurred
      before the first fill. MEASURES: Proportion who underwent appropriate diagnostic
      evaluation of androgen deficiency and ascertainment of contraindications for
      testosterone therapy during the year before receiving their first testosterone
      dispensing. RESULTS: New testosterone dispensing in VA increased from 20,437 in
      FY09 to 36,394 in FY12. Only 3.1% of men who received testosterone had 2 or more
      low (total or free) testosterone levels in the morning, LH and/or FSH level
      measured, and no contraindications to testosterone therapy. A total of 16.5% did
      not have their testosterone level checked at all. Among those prescribed therapy,
      1.4% had prostate cancer, 7.6% had obstructive sleep apnea, and 3.5% had elevated
      hematocrit at baseline. CONCLUSIONS: Only a small proportion of men receiving
      testosterone in VA underwent appropriate testing, and some received this therapy
      despite important contraindications. Promoting a more uniform application of
      clinical guidelines may facilitate appropriate use of testosterone.

PMID- 26196851
TI  - Can prokineticin prevent obesity and insulin resistance?
AB  - PURPOSE OF REVIEW: Because of its increasing prevalence and morbi-mortality,
      obesity is a major health problem. Obesity etiology includes a combination of
      excess dietary calories and decreased physical activity, coupled with either
      predisposing genetic factors or metabolic disorders such as insulin resistance.
      Adipose tissue secretes several metabolically important proteins known as
      'adipokines' that play a major role in obesity and insulin resistance. High
      levels of a newly identified group of adipokines, called prokineticins, have been
      found in obese adipose tissues. Prokineticins are peptide hormones released
      principally from macrophages and reproductive organs. They act on the G protein
      coupled receptors PKR1 and PKR2. This review aims to provide an overview of
      current knowledge of the role of prokineticins and their receptors in the
      development of obesity and insulin resistance. RECENT FINDINGS: The principal
      biological effect of prokineticins in the central nervous system is the control
      of food intake. Nevertheless, peripheral biological effects of prokineticin are
      associated with increasing insulin sensitivity and suppressing the adipose tissue
      expansion. SUMMARY: We outline the biological significance of the central and
      peripheral effects of prokineticins, and the potential of their receptors as
      targets for the treatment of obesity and insulin resistance.

PMID- 26196852
TI  - Novel Sample Preparation Technique To Improve Spectromicroscopic Analyses of
      Micrometer-Sized Particles.
AB  - Microscale processes occurring at biogeochemical interfaces in soils and
      sediments have fundamental impacts on phenomena at larger scales. To obtain the
      organo-mineral associations necessary for the study of biogeochemical interfaces,
      bulk samples are usually fractionated into microaggregates or micrometer-sized
      single particles. Such fine-grained mineral particles are often prepared for
      nanoscale secondary ion mass spectroscopy (NanoSIMS) investigations by depositing
      them on a carrier. This introduces topographic differences, which can strongly
      affect local sputtering efficiencies. Embedding in resin causes undesired C
      impurities. We present a novel method for preparing polished cross-sections of
      micrometer-sized primary soil particles that overcomes the problems of topography
      and C contamination. The particles are coated with a marker layer, embedded, and
      well-polished. The interpretation of NanoSIMS data is assisted by energy
      dispersive X-ray spectroscopy on cross-sections prepared by a focused ion beam.
      In the cross-sections, organic assemblages on the primary soil particles become
      visible. This novel method significantly improves the quality of NanoSIMS
      measurements on grainy mineral samples, enabling better characterization of soil
      biogeochemical interfaces. In addition, this sample preparation technique may
      also improve results from other (spectro-) microscopic techniques.

PMID- 26196854
TI  - A Molecular Diode with a Statistically Robust Rectification Ratio of Three Orders
      of Magnitude.
AB  - This paper describes a molecular diode with high, statistically robust,
      rectification ratios R of 1.1 * 10(3). These diodes operate with a new mechanism
      of charge transport based on sequential tunneling involving both the HOMO and
      HOMO-1 positioned asymmetrically inside the junction. In addition, the diodes are
      stable and withstand voltage cycling for 1500 times, and the yield in working
      junctions is 90%. 

PMID- 26196853
TI  - The Capacity of Eye Care Services for Patients with Glaucoma in Botswana.
AB  - PURPOSE: To evaluate current delivery of glaucoma care in Botswana; in
      particular, the service infrastructure available and glaucoma-related workload.
      METHODS: A multi-center cross-sectional study was undertaken comprising
      government eye care institutions and ophthalmic personnel across Botswana. Data
      on human resources, equipment types and numbers, diagnostic criteria routinely
      used, treatments routinely provided, and new and repeat glaucoma consultations
      were obtained through quantitative and qualitative surveys. RESULTS: In 27
      government eye care institutions there were two general ophthalmologists, neither
      of whom had a subspecialty interest in glaucoma, 64 ophthalmic nurses, two
      optometrists, one low vision therapist, one refractionist, and two equipment
      technicians. Only 8.5% of available ophthalmic human resources were taken up with
      provision of glaucoma care. About 1/3 of hospitals did not have tonometers, most
      primary hospitals lacked slit lamp biomicroscopes and most hospitals lacked
      sensitive diagnostic equipment. A diagnosis of glaucoma was made by either an
      ophthalmic nurse or an ophthalmologist, but only 10% of institutions could meet
      recommendations for follow-up assessment. Topical glaucoma medications were
      prescribed by almost all hospital clinics, usually by ophthalmic nurses. Drug
      choices were largely determined by local availability. Glaucoma surgery accounted
      for 0.8% of total eye operations. Glaucoma patients took up 8.5% of total clinic
      visits. The total number of glaucoma visits was highest in the two hospitals with
      ophthalmologists. New glaucoma cases took up 10.3% of total glaucoma visits.
      CONCLUSION: This study highlights the challenges faced in caring for glaucoma
      patients in Botswana; in particular, lack of professional human resources,
      equipment and availability of effective treatments.

PMID- 26196855
TI  - Risk Factors for Serogroup C Meningococcal Disease during Outbreak among Men who
      Have Sex with Men, New York City, New York, USA.
AB  - Risk factors for illness during a serogroup C meningococcal disease outbreak
      among men who have sex with men in New York City, New York, USA, in 2012-2013
      included methamphetamine and cocaine use and sexually transmitted infections.
      Outbreak investigations should consider routinely capturing information regarding
      drug use and sex-related risk factors. 

PMID- 26196856
TI  - Effect of carbon monoxide on gene expression in cerebrocortical astrocytes:
      Validation of reference genes for quantitative real-time PCR.
AB  - Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR)
      is a widely used technique to characterize changes in gene expression in complex
      cellular and tissue processes, such as cytoprotection or inflammation. The
      accurate assessment of changes in gene expression depends on the selection of
      adequate internal reference gene(s). Carbon monoxide (CO) affects several
      metabolic pathways and de novo protein synthesis is crucial in the cellular
      responses to this gasotransmitter. Herein a selection of commonly used reference
      genes was analyzed to identify the most suitable internal control genes to
      evaluate the effect of CO on gene expression in cultured cerebrocortical
      astrocytes. The cells were exposed to CO by treatment with CORM-A1 (CO releasing
      molecule A1) and four different algorithms (geNorm, NormFinder, Delta Ct and
      BestKeeper) were applied to evaluate the stability of eight putative reference
      genes. Our results indicate that Gapdh (glyceraldehyde-3-phosphate dehydrogenase)
      together with Ppia (peptidylpropyl isomerase A) is the most suitable gene pair
      for normalization of qRT-PCR results under the experimental conditions used. Pgk1
      (phosphoglycerate kinase 1), Hprt1 (hypoxanthine guanine phosphoribosyl
      transferase I), Sdha (Succinate Dehydrogenase Complex, Subunit A), Tbp (TATA box
      binding protein), Actg1 (actin gamma 1) and Rn18s (18S rRNA) genes presented less
      stable expression profiles in cultured cortical astrocytes exposed to CORM-A1 for
      up to 60 min. For validation, we analyzed the effect of CO on the expression of
      Bdnf and bcl-2. Different results were obtained, depending on the reference genes
      used. A significant increase in the expression of both genes was found when the
      results were normalized with Gapdh and Ppia, in contrast with the results
      obtained when the other genes were used as reference. These findings highlight
      the need for a proper and accurate selection of the reference genes used in the
      quantification of qRT-PCR results in studies on the effect of CO in gene
      expression.

PMID- 26196857
TI  - An electrochemical approach to graphene oxide coated sulfur for long cycle life.
AB  - Owing to the possibilities of achieving high theoretical energy density and
      gravimetric capacity, sulfur has been considered as a promising cathode material
      for rechargeable lithium batteries. However, sulfur shows rapid capacity fading
      due to the irreversible loss of soluble polysulfides and the decrease in active
      sites needed for conducting agents. Furthermore, the low electrical conductivity
      of sulfur hampers the full utilization of active materials. Here we report that
      graphene oxide coated sulfur composites (GO-S/CB) exhibit improved
      electrochemical stability as well as enhanced rate performance, evidenced by
      various electrochemical analyses. The cyclic voltammetry and the galvanostatic
      cycling analysis revealed that the GO plays key roles in homogenizing the
      nanocomposite structures of the electrodes, in improving the electrochemical
      contact, and in minimizing the loss of soluble polysulfide intermediates. An
      electrochemical impedance spectroscopy analysis also confirms the enhanced
      structural stability of the GO-S/CB composites after battery operation. As a
      result, the GO-S/CB exhibited excellent cycle stability and specific capacity as
      high as ~723.7 mA h g(-1) even after 100 cycles at 0.5 C. 

PMID- 26196858
TI  - Voluntary Exercise Training: Analysis of Mice in Uninjured, Inflammatory, and
      Nerve-Injured Pain States.
AB  - Both clinical and animal studies suggest that exercise may be an effective way to
      manage inflammatory and neuropathic pain conditions. However, existing animal
      studies commonly use forced exercise paradigms that incorporate varying degrees
      of stress, which itself can elicit analgesia, and thus may complicate the
      interpretation of the effects of exercise on pain. We investigated the analgesic
      potential of voluntary wheel running in the formalin model of acute inflammatory
      pain and the spared nerve injury model of neuropathic pain in mice. In uninjured,
      adult C57BL/6J mice, 1 to 4 weeks of exercise training did not alter nociceptive
      thresholds, lumbar dorsal root ganglia neuronal excitability, or hindpaw
      intraepidermal innervation. Further, exercise training failed to attenuate
      formalin-induced spontaneous pain. Lastly, 2 weeks of exercise training was
      ineffective in reversing spared nerve injury-induced mechanical hypersensitivity
      or in improving muscle wasting or hindpaw denervation. These findings indicate
      that in contrast to rodent forced exercise paradigms, short durations of
      voluntary wheel running do not improve pain-like symptoms in mouse models of
      acute inflammation and peripheral nerve injury.

PMID- 26196860
TI  - Two New Crystals in Li(m)Cs(n)B(m+n)O2(m+n) (m + n = 5, 7; m > n) Series:
      Noncentrosymmetric Li5Cs2B7O14 and Centrosymmetric Li4CsB5O10.
AB  - With the introduction of an alkali metal into the B-O framework, two new alkali
      metal borate crystals, Li5Cs2B7O14 and Li4CsB5O10, have been obtained for the
      first time. Both compounds obey a general formula of Li(m)Cs(n)B(m+n)O2(m+n) (m +
      n = 5, 7; m > n). The two crystals have different three-dimensional (3D)
      framework structures composed by LiOn (n = 4, 5), CsO10, BO3, and BO4 units.
      Li5Cs2B7O14 crystallizes into the polar and noncentrosymmetric space group Ama2,
      while Li4CsB5O10 belongs to the nonpolar and centrosymmetric space group P21/c.
      Detailed structure comparison analysis indicates that the different arrangements
      of the anionic groups in Li(m)Cs(7-m)B7O14 (m = 4, 5) and Li(m)Cs(5-m)B5O10 (m =
      3, 4) may arise from the cation size effects, bond-valence requirements, and
      differences of coordination environment. In addition, in order to get better
      understandings of electronic structures and linear optical properties, we also
      carried out first-principle theoretical studies.

PMID- 26196859
TI  - Association of Rotating Night Shift Work with BMI and Abdominal Obesity among
      Nurses and Midwives.
AB  - BACKGROUND: Mounting epidemiological evidence suggests that night shift work may
      contribute to the etiology of increased body weight. The present study aimed to
      examine association between rotating night shift work and body mass index (BMI),
      and abdominal adiposity respectively among nurses and midwives. METHODS: A cross
      sectional study was conducted among 724 female nurses and midwives, aged 40-60
      years (354 rotating night shift and 370 daytime workers) in Lodz, Poland, between
      2008 and 2011. Information about occupational history and potential confounders
      was collected during personal interviews. Anthropometric measurements of body
      weight, height, waist (WC) and hip (HC) circumference were made, and body mass
      index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) were
      calculated. GLM regression models and multinomial logit regression models were
      fitted to explore the association between night shift work and anthropometric
      parameters, with adjustment for age, body silhouette at age 20, current smoking
      status, packyears, marital status, and menopausal hormone therapy use. RESULTS:
      Cumulative night shift work showed significant associations with BMI, WC, HC and
      WHtR, with BMI increasing by 0.477 kg/m2 per 1000 night duties and by 0.432 kg/m2
      per 10000 night shift hours, WC increasing respectively by 1.089 cm and 0.99 cm,
      and HC by 0.72 cm and WHtR by 0.007 cm for both metrics. Both current and
      cumulative night work was associated with obesity (BMI>=30kg/m2), with OR=3.9
      (95%CI:1.5-9.9), in women reporting eight or more night shifts per month.
      CONCLUSION: The results of the study support the previously reported relations
      between night shift work and development of obesity.

PMID- 26196861
TI  - Functional Classification of Uncultured "Candidatus Caldiarchaeum subterraneum"
      Using the Maple System.
AB  - In this study, the metabolic and physiological potential evaluator system based
      on Kyoto Encyclopedia of Genes and Genomes (KEGG) functional modules was employed
      to establish a functional classification of archaeal species and to determine the
      comprehensive functions (functionome) of the previously uncultivated thermophile
      "Candidatus Caldiarchaeum subterraneum" (Ca. C. subterraneum). A phylogenetic
      analysis based on the concatenated sequences of proteins common among 142 archaea
      and 2 bacteria, and among 137 archaea and 13 unicellular eukaryotes suggested
      that Ca. C. subterraneum is closely related to thaumarchaeotic species.
      Consistent with the results of the phylogenetic analysis, clustering and
      principal component analyses based on the completion ratio patterns for all KEGG
      modules in 79 archaeal species suggested that the overall metabolic and
      physiological potential of Ca. C. subterraneum is similar to that of
      thaumarchaeotic species. However, Ca. C. subterraneum possessed almost no genes
      in the modules required for nitrification and the hydroxypropionate
      hydroxybutyrate cycle for carbon fixation, unlike thaumarchaeotic species.
      However, it possessed all genes in the modules required for central carbohydrate
      metabolism, such as glycolysis, pyruvate oxidation, the tricarboxylic acid (TCA)
      cycle, and the glyoxylate cycle, as well as multiple sets of sugar and branched
      chain amino acid ABC transporters. These metabolic and physiological features
      appear to support the predominantly aerobic character of Ca. C. subterraneum,
      which lives in a subsurface thermophilic microbial mat community with a
      heterotrophic lifestyle.

PMID- 26196862
TI  - Preservation of Helicobacter pylori CagA Translocation and Host Cell
      Proinflammatory Responses in the Face of CagL Hypervariability at Amino Acid
      Residues 58/59.
AB  - Carriage of the CagA oncoprotein by the human gastric cancer-associated pathogen
      Helicobacter pylori is significantly associated with this typically benign
      chronic infection advancing to a potentially fatal outcome. However it remains to
      be elucidated why only a small subset of individuals infected with H. pylori CagA
      positive strains develops gastric cancer. H. pylori translocates CagA into host
      cells using a type IV secretion apparatus that interacts with host integrin
      receptors via a three-amino-acid-residue RGD motif on the H. pylori protein CagL.
      The RGD motif of CagL also plays a major role in the induction of proinflammatory
      responses. Upstream of this motif is a conserved glycine flanked by four
      hypervariable amino acid residues (residues 58, 59, 61 and 62). Certain amino
      acid polymorphisms at 58 and 59 are significantly prevalent in strains from
      gastric cancer patients in particular geographic regions; Y58E59 is seen in
      Taiwan and D58K59 in India. In light of the seemingly contradictory findings of
      recent CagL mutagenesis studies, we have examined the contribution of sequence
      promiscuity specifically at CagL residues 58 and 59 to CagA translocation and H.
      pylori-mediated proinflammatory responses of gastric epithelial cells. Using
      isogenic mutants of H. pylori strains P12 and 26695 with amino acid substitutions
      at CagL residues 58 and 59, we determined that carriage of the polymorphisms
      Y58E59, D58K59, D58E59, N58E59 or N58K59 did not significantly alter the capacity
      of H. pylori to translocate CagA into, or induce IL-8 secretion in, host cells.
      Our findings, together with other recently published data, suggest that the
      variation at CagL residues 58 and 59 does not influence type IV secretion system
      function in isolation, but rather may work in concert with particular
      polymorphisms elsewhere in CagL to modulate disease progression.

PMID- 26196863
TI  - Probing the Active Surface Sites for CO Reduction on Oxide-Derived Copper
      Electrocatalysts.
AB  - CO electroreduction activity on oxide-derived Cu (OD-Cu) was found to correlate
      with metastable surface features that bind CO strongly. OD-Cu electrodes prepared
      by H2 reduction of Cu2O precursors reduce CO to acetate and ethanol with nearly
      50% Faradaic efficiency at moderate overpotential. Temperature-programmed
      desorption of CO on OD-Cu revealed the presence of surface sites with strong CO
      binding that are distinct from the terraces and stepped sites found on
      polycrystalline Cu foil. After annealing at 350  degrees C, the surface-area
      corrected current density for CO reduction is 44-fold lower and the Faradaic
      efficiency is less than 5%. These changes are accompanied by a reduction in the
      proportion of strong CO binding sites. We propose that the active sites for CO
      reduction on OD-Cu surfaces are strong CO binding sites that are supported by
      grain boundaries. Uncovering these sites is a first step toward understanding the
      surface chemistry necessary for efficient CO electroreduction. 

PMID- 26196864
TI  - A Genetic Basis for Motivated Exercise.
AB  - Prior research has demonstrated a genetic basis for motivated exercise, with
      evidence of a role for nescient helix-loop-helix-2 (NHLH2/Nhlh2). Nhlh2
      transcriptionally regulates the monoamine oxidase A (MAO-A) gene. This article
      examines the evidence for the hypothesis that polymorphisms in NHLH2 or MAO-A
      contribute to differences in the human motivation for exercise and physical
      activity. The genetic pathways that link exercise and motivation are discussed. 

PMID- 26196865
TI  - Testosterone and Adult Male Bone: Actions Independent of 5alpha-Reductase and
      Aromatase.
AB  - Androgens and estrogens influence skeletal development and maintenance in males.
      However, the relative contributions of the circulating sex steroid hormones that
      originate from testicular/adrenal secretion versus those produced locally in bone
      via intracrine action require further elucidation. Our novel hypothesis is that
      testosterone exerts direct protective effects on the adult male skeleton
      independently of the actions of 5alpha-reductase or aromatase. 

PMID- 26196866
TI  - Heterogeneous Loading of the Human Achilles Tendon In Vivo.
AB  - The free Achilles tendon is considered a homogeneous structure that transmits
      muscular force in a linear manner. However, the tendon undergoes longitudinal
      rotation and is separated in mechanically independent segments with distinct
      mechanical and material tissue properties. The present article examines the
      hypothesis that the human Achilles tendon is loaded asymmetrically and undergoes
      heterogeneous deformation during movement. 

PMID- 26196867
TI  - Impact of Maternal Exercise during Pregnancy on Offspring Chronic Disease
      Susceptibility.
AB  - Maternal behaviors during pregnancy have been reported to impact offspring health
      in adulthood. In this article we explore the novel hypothesis that exercise
      during pregnancy can protect against chronic disease susceptibility in the
      offspring. To date, research has demonstrated that improvements in metabolic
      outcomes, cardiovascular risk, and cancer can occur in response to maternal
      exercise during pregnancy. 

PMID- 26196868
TI  - Hypoxanthine: A Universal Metabolic Indicator of Training Status in Competitive
      Sports.
AB  - Cardiorespiratory and biochemical indicators typically used by contemporary elite
      athletes seem to have limited applicability. According to some recent studies,
      purine metabolism better reflects exercise response and muscle adaptation in this
      group. We propose using purine derivatives, especially plasma hypoxanthine
      concentration, as indicators of training status in consecutive training phases in
      highly trained athletes. 

PMID- 26196869
TI  - Clinical Classification of Heart Failure Patients Using Cardiac Function during
      Exercise.
AB  - An effective approach for determining the clinical classification of heart
      failure (HF) patients is to estimate cardiac hemodynamics during exercise. This
      approach is strengthened further when measurements including cardiac power are
      used to describe cardiac hemodynamics. We hypothesize that cardiac power
      quantifies the hemodynamic and pressure-generating capability of the heart,
      relating with exercise tolerance better than traditional measurements in HF. 

PMID- 26196870
TI  - The Role of Exercise-Induced Cardiovascular Adaptation in Brain Health.
AB  - Regular aerobic exercise improves brain health; however, a potential dose
      response relationship and the underling physiological mechanisms remain unclear.
      Existing data support the following hypotheses: 1) exercise-induced
      cardiovascular adaptation plays an important role in improving brain perfusion,
      structure, and function, and 2) a hormetic relation seems to exist between the
      intensity of exercise and brain health, which needs to be further elucidated. 

PMID- 26196871
TI  - Correction: Validation of the New Lucerne ICF Based Multidisciplinary Observation
      Scale (LIMOS) for Stroke Patients.

PMID- 26196872
TI  - Moonflowers: Heart-racing Deliriants behind Hanaoka's Mafutsusan (Year 1804, Part
      1).

PMID- 26196873
TI  - Monkshoods: Heart-stopping Neurotoxins behind Hanaoka's Mafutsusan (Year 1804,
      Part 2).

PMID- 26196874
TI  - Balanced Anesthesia with Moonflowers and Monkshoods: Behind Hanaoka's Mafutsusan
      (Year 1804, Part 3).

PMID- 26196875
TI  - Nephrotoxicity by Administration of Hyperchloremic Solutions.

PMID- 26196876
TI  - Is Hydroxyethyl Starch 130/0.4 Safe for the Kidney in Noncardiac Surgical
      Patients?

PMID- 26196877
TI  - Lack of Nephrotoxicity of Hydroxyethyl Starch 130/0.4 When Used in Surgery.

PMID- 26196878
TI  - In Reply.

PMID- 26196879
TI  - Being Conscious of Methodological Pitfalls in Functional Brain Network Analysis.

PMID- 26196880
TI  - In Reply.

PMID- 26196881
TI  - 49 Mathoura Road: To Grow Up, You Have to Leave Home.

PMID- 26196882
TI  - In Reply.

PMID- 26196883
TI  - Transfusion-related Acute Lung Injury: More Questions Than Answers?

PMID- 26196884
TI  - Blood Conservation Techniques and Platelet Function in Cardiac Surgery:
      Retraction.

PMID- 26196890
TI  - Randomized Controlled Trials vs. Administrative Database Studies.

PMID- 26196891
TI  - Occupational Exposure to Dromedaries and Risk for MERS-CoV Infection, Qatar, 2013
      2014.
AB  - We determined the presence of neutralizing antibodies to Middle East respiratory
      syndrome coronavirus in persons in Qatar with and without dromedary contact.
      Antibodies were only detected in those with contact, suggesting dromedary
      exposure as a risk factor for infection. Findings also showed evidence for
      substantial underestimation of the infection in populations at risk in Qatar. 

PMID- 26196892
TI  - Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced
      Insulin Resistance in Rats.
AB  - AIMS: To evaluate whether pharmacological TLR4 inhibition protects against acute
      and chronic fat-induced insulin resistance in rats. MATERIALS AND METHODS: For
      the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg
      i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline
      infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the
      chronic experiment, rats were subcutaneously implanted with a slow-release pellet
      of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a
      low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp.
      RESULTS: Acute experiment; the lipid-induced reduction (18%) in insulin
      stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect
      of E5564 was more robust), suggesting improved peripheral insulin action. Insulin
      was able to suppress hepatic glucose production (HGP) in saline- but not lipid
      treated rats. TAK-242, but not E5564, partially restored this effect, suggesting
      improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the
      HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats
      fed a HFD and TAK-242 had no effect on HGP. CONCLUSIONS: Pharmacological TLR4
      inhibition provides partial protection against acute and chronic fat-induced
      insulin resistance in vivo.

PMID- 26196893
TI  - Aqueous, Unfolded OmpA Forms Amyloid-Like Fibrils upon Self-Association.
AB  - Unfolded outer membrane beta-barrel proteins have been shown to self-associate in
      the absence of lipid bilayers. We previously investigated the formation of high
      molecular weight species by OmpA, with both the transmembrane domain alone and
      the full-length protein, and discovered that the oligomeric form contains non
      native beta-sheet structure. We have further probed the conformation of self
      associated OmpA by monitoring binding to Thioflavin T, a dye that is known to
      bind the cross-beta a structure inherent in amyloid fibrils, and by observing the
      species by electron microscopy. The significant increase in fluorescence
      indicative of Thioflavin T binding and the appearance of fibrillar species by
      electron microscopy verify that the protein forms amyloid-like fibril structures
      upon oligomerization. These results are also consistent with our previous kinetic
      analysis of OmpA self-association that revealed a nucleated growth polymerization
      mechanism, which is frequently observed in amyloid formation. The discovery of
      OmpA's ability to form amyloid-like fibrils provides a new model protein with
      which to study fibrillization, and implicates periplasmic chaperone proteins as
      capable of inhibiting fibril formation. 

PMID- 26196894
TI  - Intestinal obstruction is a rare complication of ondansetron exposure in
      hyperemesis gravidarum.

PMID- 26196895
TI  - Criteria for determining whether mismatch responses exist in animal models: Focus
      on rodents.
AB  - The mismatch negativity (MMN) component of the auditory event-related potential,
      elicited in response to unexpected stimuli in the auditory environment, has great
      value for cognitive neuroscience research. It is changed in several
      neuropsychiatric disorders such as schizophrenia. The ability to measure and
      manipulate MMN-like responses in animal models, particularly rodents, would
      provide an enormous opportunity to learn more about the neurobiology underlying
      MMN. However, the MMN in humans is a very specific phenomenon: how do we decide
      which features we should focus on emulating in an animal model to achieve the
      highest level of translational validity? Here we discuss some of the key features
      of MMN in humans and summarise the success with which they have been translated
      into rodent models. Many studies from several different labs have successfully
      shown that the rat brain is capable of generating deviance detection responses
      that satisfy of the criteria for the human MMN. 

PMID- 26196896
TI  - The neural evidence of the reflected appraisal process as a main path for
      learning about one's self-knowledge of personality.
AB  - Self-knowledge has been defined as the accurate self-perceptions about how one
      typically thinks, feels, and behaves, and awareness of how those patterns are
      interpreted by others. Previous research has noted that the introspection and the
      reflected appraisal processes are two main avenues for learning about the self
      and that self-knowledge might be fully realized through the use of reflected
      appraisal from close others. However, due to the methodological difficulty in
      linking people's ratings on a trait to their behaviors, accuracy research using a
      behavioral criterion is quite limited. The current work examined the main source
      of learning about one's self-knowledge by investigating the time course of
      attention deployment both in the process of introspection and that of reflected
      appraisal. Twenty-five college students were first asked to rate their
      impressions of their classmates as well as a familiar other using personality
      trait adjectives. Their electrophysiological data were then collected using the
      event-related potential (ERP) technology while they judged to which extent (1) an
      adjective can describe the self, (2) an adjective can describe a familiar other,
      (3) they agree with an adjective that their classmates believe can describe the
      self, and (4) they agree with an adjective that their classmates believe can
      describe a familiar other. Our electrophysiological data showed that classmates'
      positive evaluation of one's own trait elicited larger P2 than the positive self
      evaluation of one's own trait. Further, classmates' negative evaluation of one's
      own trait elicited larger late positive component (LPC) than the negative self
      evaluation of one's own trait. Results suggest that people allocate more
      attention to the process of reflected appraisal compared to the process of
      introspection, which further suggests that the reflected appraisal process might
      be the main source in learning about one's self-knowledge of personality. 

PMID- 26196897
TI  - Competitive interactions in somatosensory cortex for concurrent vibrotactile
      stimulation between and within hands.
AB  - We investigated competitive neural interactions for processing resources during
      sustained spatial attention in somatosensation. Participants received concurrent
      vibrotactile stimulation at different frequencies to either non-adjacent left
      hand fingers (within-hand) or fingers on two hands (between-hands) for 4500 ms to
      elicit steady-state somatosensory evoked potentials (SSSEPs). They attended to
      either one or both stimulated locations, respectively, and responded to rare
      events embedded in the ongoing stream. Behavioral and electrophysiological
      results revealed competitive interaction of simultaneous stimulation with overall
      smaller SSSEP amplitudes and poorer behavioral performance in the within-hand
      condition. Spatial proximity of stimulation did not affect the magnitude of
      attentional gain, it resulted in the occurrence of an intermodulation frequency
      indicating integrative stimulus processing in the within-hand condition.
      Obviously, while this integrative stimulus processing resulted in or was a result
      of greater intra-hemispheric competitive interactions, attention acted additively
      as a signal gain, which was independent of spatial competition.

PMID- 26196898
TI  - Exposure to social-evaluative video clips: Neural, facial-muscular, and
      experiential responses and the role of social anxiety.
AB  - Engaging in social interaction often implies being evaluated. Receiving positive
      evaluations from others may elicit affiliative emotions whereas negative
      evaluations are likely to trigger withdrawal and defensive social behavior.
      Evolution has equipped humans with efficient systems to detect, appraise, and
      regulate responses to such evaluative communications and to express complementary
      responses. The current study investigates neural, facial-muscular, and
      experiential responses to short videos delivering neutral, positive, and negative
      audiovisual messages as well as their relation to individual differences in
      social anxiety. Fifty-eight participants (32 female) watched 90 videos with male
      and female actors displaying positive, negative, and neutral statements.
      Experientially, ratings of valence and arousal showed the expected category
      differences. Neurally, larger centro-parietal late positive event related
      potentials were found for emotional (positive and negative) videos compared to
      neutral videos. Facial electromyography revealed reduced corrugator muscle and
      increased zygomaticus major muscle activity for positive videos compared to
      neutral and negative videos. Cognitive components of social anxiety were related
      to a more unpleasant experience of negative videos and a less pleasant experience
      of positive videos. Thus, a set of neural, facial-muscular, and experiential
      responses contribute to social interaction in the context of relatively
      naturalistic social-evaluative stimuli. 

PMID- 26196899
TI  - The window of my eyes: Task disengagement and mental fatigue covary with pupil
      dynamics.
AB  - Although mental fatigue is a complex, multi-facetted state that involves changes
      in motivation, cognition, and mood, one of its main characteristics is reduced
      task engagement. Despite its relevance for performance and safety, knowledge
      about the underlying neurocognitive processes in mental fatigue is still limited.
      Inspired by the idea that central norepinephrine plays an important role in
      regulating task engagement, we test a set of predictions that have been derived
      from recent studies that relate pupil dynamics to the levels of norepinephrine in
      the brain. Participants worked on a 2-back task for 2h while we used pupil
      measures to further explore the link between task engagement and the effects of
      mental fatigue. We hypothesized that baseline pupil diameter and stimulus-evoked
      pupil dilations decrease with increasing fatigue. Also, because previous studies
      have shown that the effects of fatigue are reversible by increasing the task
      rewards, we hypothesized that increasing the task rewards after 2h on the task
      would restore these pupil measures to pre-fatigue levels. While we did not find a
      decrease in baseline pupil diameter, we found that increasing mental fatigue
      coincided with diminished stimulus-evoked pupil dilation. Also, we confirmed that
      when sufficient rewards were presented to a fatigued individual, the pupil
      dilations could be restored. This supports the view that motivational factors are
      important in predicting engagement versus disengagement during fatigue. 

PMID- 26196900
TI  - Happy and less inhibited? Effects of positive mood on inhibitory control during
      an antisaccade task revealed using topographic evoked potential mapping.
AB  - Affective states might influence inhibitory control, a cognitive process
      fundamental for goal adaptive behavior. Here, we recorded high-density EEG while
      participants performed an antisaccade task, after the induction of a happy (n=20)
      or neutral (n=20) mood, to compare the same inhibition-related processes across
      these two affective contexts. Topographical evoked potential mapping methods were
      used to characterize changes in the electric field depending on mood and saccade
      type (pro vs. anti) concurrently. Results showed that prior to target onset, the
      CNV component was enhanced for anti- compared to prosaccades, selectively in the
      neutral mood group. Following target onset, the topography of the N2 was more
      strongly expressed in the happy mood group, and was also altered by saccade type.
      The subsequent P3 components were not modulated by mood. We discuss these new
      findings in light of recent neurobiological and neuropsychological models that
      posit that positive affect dynamically changes cognitive control. 

PMID- 26196901
TI  - A Field Study in Benin to Investigate the Role of Mosquitoes and Other Flying
      Insects in the Ecology of Mycobacterium ulcerans.
AB  - BACKGROUND: Buruli ulcer, the third mycobacterial disease after tuberculosis and
      leprosy, is caused by the environmental mycobacterium M. ulcerans. There is at
      present no clear understanding of the exact mode(s) of transmission of M.
      ulcerans. Populations affected by Buruli ulcer are those living close to humid
      and swampy zones. The disease is associated with the creation or the extension of
      swampy areas, such as construction of dams or lakes for the development of
      agriculture. Currently, it is supposed that insects (water bugs and mosquitoes)
      are host and vector of M. ulcerans. The role of water bugs was clearly
      demonstrated by several experimental and environmental studies. However, no
      definitive conclusion can yet be drawn concerning the precise importance of this
      route of transmission. Concerning the mosquitoes, DNA was detected only in
      mosquitoes collected in Australia, and their role as host/vector was never
      studied by experimental approaches. Surprisingly, no specific study was conducted
      in Africa. In this context, the objective of this study was to investigate the
      role of mosquitoes (larvae and adults) and other flying insects in ecology of M.
      ulcerans. This study was conducted in a highly endemic area of Benin.
      METHODOLOGY/PRINCIPAL FINDINGS: Mosquitoes (adults and larvae) were collected
      over one year, in Buruli ulcer endemic in Benin. In parallel, to monitor the
      presence of M. ulcerans in environment, aquatic insects were sampled. QPCR was
      used to detected M. ulcerans DNA. DNA of M. ulcerans was detected in around 8.7%
      of aquatic insects but never in mosquitoes (larvae or adults) or in other flying
      insects. CONCLUSION/SIGNIFICANCE: This study suggested that the mosquitoes don't
      play a pivotal role in the ecology and transmission of M. ulcerans in the studied
      endemic areas. However, the role of mosquitoes cannot be excluded and, we can
      reasonably suppose that several routes of transmission of M. ulcerans are
      possible through the world.

PMID- 26196903
TI  - Comparison of Accelerated and Standard Hepatitis B Vaccination Schedules in High
      Risk Healthy Adults: A Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Selecting the most efficient vaccination schedule is an important
      issue. OBJECTIVE: To assess the beneficial and harmful effects of accelerated
      hepatitis B vaccination schedules in high-risk healthy adults. METHODS: We
      searched controlled trial registers of The Cochrane Library as well as MEDLINE,
      EMBASE, VIP Database for Chinese Technical Periodicals, and the Chinese National
      Knowledge Infrastructure databases for randomized controlled trials published up
      to December 2013 that compared accelerated hepatitis B vaccine schedules to the
      standard schedule in adults. The results were presented as relative risk with 95%
      confidence intervals. Fixed or random effect models were used for analysis.
      RESULTS: We identified 10 randomized trials, all with one or more methodological
      weaknesses. Compared to the standard schedule, most accelerated schedules
      resulted in higher proportions of healthy vaccines more rapidly reaching anti
      hepatitis B antibody levels >10 IU/L (P<0.05) initially and maintaining similar
      seroprotection rates after 6 months (P>0.05). Although accelerated schedules
      produced anti-hepatitis B levels higher than the standard schedule for the first
      month after the initial vaccine dose, they were significantly lower than the
      standard schedule after 6 months, except for an accelerated schedule that called
      for a fourth booster injection 12 months after the initial dose. Subjects
      administered accelerated vaccine schedules had similar compliance rate as those
      administered the standard schedule over the first 6 months of vaccination
      (relative risk = 1.00, 95% confidence interval: 0.84-1.21). CONCLUSION: For rapid
      seroconversion and almost immediate short-term protection, accelerated
      vaccination schedules could be useful for at-risk groups. However, additional
      studies on the long-term protection and effectiveness of the primary doses of
      accelerated schedules are necessary.

PMID- 26196902
TI  - Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health
      Study.
AB  - Some studies suggest that telomere length (TL) may be influenced by environmental
      exposures, including pesticides. We examined associations between occupational
      pesticide use reported at three time points and relative telomere length (RTL) in
      the Agricultural Health Study (AHS), a prospective cohort study of pesticide
      applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte
      DNA from 568 cancer-free male AHS participants aged 31-94 years with blood
      samples collected between 2006 and 2008. Self-reported information, including
      pesticide use, was collected at three time points: enrollment (1993-1997) and two
      follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated
      cumulative use (using data from all three questionnaires), and more recent use
      (using data from the last follow-up questionnaire). Multivariable linear
      regression was used to examine the associations between pesticide use (ever,
      lifetime days, intensity-weighted lifetime days (lifetime days*intensity score))
      and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57
      pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p
      trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were
      significantly associated with shorter RTL, while increasing lifetime days of
      alachlor was significantly associated with longer RTL (p-trend=0.03). Only the
      association with 2,4-D was significant after adjustment for multiple comparisons.
      Of the 40 pesticides evaluated for recent use, malathion was associated with
      shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest
      that leukocyte TL may be impacted by cumulative use and recent use of certain
      pesticides.

PMID- 26196904
TI  - Controllable Tailoring Graphene Nanoribbons with Tunable Surface Functionalities:
      An Effective Strategy toward High-Performance Lithium-Ion Batteries.
AB  - An effective, large-scale synthesis strategy for producing graphene nanoribbons
      (GNRs) with a nearly 100% yield has been proposed using a stepwise, solution
      based, lengthwise unzipping carbon nanotube (CNT) method. Detailed Raman and X
      ray photoelectron spectroscopy (XPS) analysis suggest that GNRs with tunable
      density of oxygen-containing functional groups on the GNR surfaces can be
      synthesized by adjusting the oxidant concentration during the CNT unzipping. The
      electrochemical characterization reveals that the as-produced GNRs with 42.91
      atomic percent (atom %) oxygen-containing functional groups deliver a capacity of
      437 mAh g(-1) after 100 cycles at 0.33C, while the as-produced GNRs with higher
      oxygen-containing functional groups only present a capacity of 225 mAh g(-1). On
      the basis of the electrochemical assessment and XPS analysis, the funtionals
      groups (epoxy-, carbonyl-, and carboxyl groups) in GNRs could be the effective
      contributor for the high-performance Li-ion batteries with appropriate
      adjustment. 

PMID- 26196905
TI  - Frontlines: A Work In Progress.

PMID- 26196908
TI  - Ten Questions With .... Sharon Allan.

PMID- 26196910
TI  - Ask George.

PMID- 26196911
TI  - Are We There Yet? Inching Toward Interoperability.

PMID- 26196912
TI  - Plugging Into the New CMS Power Strip Waiver.

PMID- 26196913
TI  - Operationalizing Medical Device Cybersecurity at a Tertiary Care Medical Center.

PMID- 26196914
TI  - A Roundtable Discussion: The Many Challenges Of Sterile Processing.

PMID- 26196915
TI  - HTM Plays 'Critical Role' in Patient Safety, NPSF Leader Says.

PMID- 26196917
TI  - Mobile Point-of-Care Monitors and Diagnostic Device Design.

PMID- 26196916
TI  - Hospital Takes Hard Look at Immediate-Use Steam Sterilization.

PMID- 26196918
TI  - The Importance of Having Mentors in HTM.

PMID- 26196919
TI  - A Model of Clinical Alarm Errors in Hospital.
AB  - Although there has been much attention paid recently to clinical alarms, research
      has primarily focused on particular aspects of the clinical alarm problem, such
      as how to reduce nuisance alarms. This paper takes a broad view of clinical
      alarms and develops a model of errors in alarm handling and how they affect
      patients directly. Based on reports in the literature, I estimate that alarms
      that should sound by current standards do not sound about 9% of the time.
      Additionally, about 3% of alarms that are clinically significant are ignored,
      either intentionally or because they were inaudible. However, these errors
      produce a very low rate of reported alarm-related deaths and other adverse
      effects (on the order of a couple adverse effects per 10 million alarm errors).
      While it is not yet possible to estimate the probabilities of clinical alarms
      having an adverse impact on patients other than the patient whose alarm is
      sounding, such indirect adverse effects likely occur at a low level as a result
      of disruption of staff workflow, creation of a noisy hospital environment, and
      contribution to communication difficulties. Consideration of alarms should
      include not only the patient connected to the device that is sounding, but also
      the impact of the alarm on other patients in the vicinity.

PMID- 26196920
TI  - Are Safety Standards Ever Proven to Enhance Safety?

PMID- 26196923
TI  - Meat Feeding Restricts Rapid Cold Hardening Response and Increases Thermal
      Activity Thresholds of Adult Blow Flies, Calliphora vicina (Diptera:
      Calliphoridae).
AB  - Virtually all temperate insects survive the winter by entering a physiological
      state of reduced metabolic activity termed diapause. However, there is increasing
      evidence that climate change is disrupting the diapause response resulting in non
      diapause life stages encountering periods of winter cold. This is a significant
      problem for adult life stages in particular, as they must remain mobile,
      periodically feed, and potentially initiate reproductive development at a time
      when resources should be diverted to enhance stress tolerance. Here we present
      the first evidence of protein/meat feeding restricting rapid cold hardening (RCH)
      ability and increasing low temperature activity thresholds. No RCH response was
      noted in adult female blow flies (Calliphora vicina Robineau-Desvoidy) fed a
      sugar, water and liver (SWL) diet, while a strong RCH response was seen in
      females fed a diet of sugar and water (SW) only. The RCH response in SW flies was
      induced at temperatures as high as 10 degrees C, but was strongest following 3h
      at 0 degrees C. The CTmin (loss of coordinated movement) and chill coma (final
      appendage twitch) temperature of SWL females (-0.3 +/- 0.5 degrees C and -4.9 +/-
      0.5 degrees C, respectively) was significantly higher than for SW females (-3.2
      +/- 0.8 degrees C and -8.5 +/- 0.6 degrees C). We confirmed this was not directly
      the result of altered extracellular K+, as activity thresholds of alanine-fed
      adults were not significantly different from SW flies. Instead we suggest the
      loss of cold tolerance is more likely the result of diverting resource allocation
      to egg development. Between 2009 and 2013 winter air temperatures in Birmingham,
      UK, fell below the CTmin of SW and SWL flies on 63 and 195 days, respectively,
      suggesting differential exposure to chill injury depending on whether adults had
      access to meat or not. We conclude that disruption of diapause could
      significantly impact on winter survival through loss of synchrony in the timing
      of active feeding and reproductive development with favourable temperature
      conditions. 

PMID- 26196925
TI  - Stories in Games for Health: More Pros or Cons?
AB  - There has been a debate about whether entertainment videogames should incorporate
      story or narrative. A concern has been whether story cut scenes break game
      immersion, and thereby minimize the fun of gameplay. Alternatively, games for
      health (G4H) have an agenda that goes beyond just having fun. The possible role
      of story in G4H has not been thoroughly addressed. We have assembled a group of
      experts who have worked with stories in G4H, and asked some pointed questions. 

PMID- 26196922
TI  - Genome-Wide Survey and Analysis of Microsatellite Sequences in Bovid Species.
AB  - Microsatellites or simple sequence repeats (SSRs) have become the most popular
      source of genetic markers, which are ubiquitously distributed in many eukaryotic
      and prokaryotic genomes. This is the first study examining and comparing SSRs in
      completely sequenced genomes of the Bovidae. We analyzed and compared the number
      of SSRs, relative abundance, relative density, guanine-cytosine (GC) content and
      proportion of SSRs in six taxonomically different bovid species: Bos taurus,
      Bubalus bubalis, Bos mutus, Ovis aries, Capra hircus, and Pantholops hodgsonii.
      Our analysis revealed that, based on our search criteria, the total number of
      perfect SSRs found ranged from 663,079 to 806,907 and covered from 0.44% to 0.48%
      of the bovid genomes. Relative abundance and density of SSRs in these Bovinae
      genomes were non-significantly correlated with genome size (Pearson, r < 0.420, p
      > 0.05). Perfect mononucleotide SSRs were the most abundant, followed by the
      pattern: perfect di- > tri- > penta- > tetra- > hexanucleotide SSRs. Generally,
      the number of SSRs, relative abundance, and relative density of SSRs decreased as
      the motif repeat length increased in each species of Bovidae. The most GC-content
      was in trinucleotide SSRs and the least was in the mononucleotide SSRs in the six
      bovid genomes. The GC-contents of tri- and pentanucleotide SSRs showed a great
      deal of similarity among different chromosomes of B. taurus, O. aries, and C.
      hircus. SSR number of all chromosomes in the B. taurus, O.aries, and C. hircus is
      closely positively correlated with chromosome sequence size (Pearson, r > 0.980,
      p < 0.01) and significantly negatively correlated with GC-content (Pearson, r < 
      0.638, p < 0.01). Relative abundance and density of SSRs in all chromosomes of
      the three species were significantly negatively correlated with GC-content
      (Pearson, r < -0.333, P < 0.05) but not significantly correlated with chromosome
      sequence size (Pearson, r < -0.185, P > 0.05). Relative abundances of the same
      nucleotide SSR type showed great similarity among different chromosomes of B.
      taurus, O. aries, and C. hircus.

PMID- 26196926
TI  - A European Profile of Games for Health.
AB  - October is time for the Games for Health Europe meeting in Amsterdam, The
      Netherlands. Games for Health Journal would like to highlight exciting
      developments in games for health in Europe by asking European members of our
      Editorial Board to comment on what developments they see. 

PMID- 26196927
TI  - A Game-Based Simulation Utilizing Virtual Humans to Train Physicians to Screen
      and Manage the Care of Patients with Mental Health Disorders.
AB  - Every year, one in four American adults suffers from a diagnosable mental
      disorder, yet most of them go untreated, creating a significant public health
      challenge. This challenge is compounded by large-scale disasters, which can cause
      an influx of primary care patients presenting with physical symptoms that mask
      mental health disorders. Primary care providers (PCPs) are usually the first
      point of contact for those patients; thus there exist crucial opportunities to
      detect and address nonphysical disorders in primary care settings that would
      improve patient outcomes and quality of care. Unfortunately, many PCPs view
      mental health as separate from the services that they provide, and the majority
      of them have received little training during or after medical or nursing school
      about risk factors, symptoms, and treatment options. To help integrate behavioral
      health into primary care, Kognito Interactive developed "At-Risk in Primary
      Care," an online game-based simulation that integrates role-play conversations
      with virtual humans to train PCPs to screen patients for mental health disorders,
      perform brief behavioral interventions using motivational interviewing (MI),
      refer patients, and integrate behavioral health into their treatment while
      building patients' intrinsic motivation to adhere to it. Preliminary findings on
      the implementation of this game in New York City show significant increases in
      skill and motivation to screen patients, conduct behavioral interventions, and
      refer patients to specialized care. These results show the promise of innovative
      technology-based solutions to integrate mental health training in primary care. 

PMID- 26196928
TI  - New-Generation Active Videogaming Maintains Energy Expenditure in Children Across
      Repeated Bouts.
AB  - OBJECTIVE: Active videogames (AVGs) remain popular among 10-15-year-old children.
      The Xbox 360 KinectTM from Microsoft (Redmond, WA) represents a new generation of
      AVGs where body movements are used to control gameplay. The purpose of this study
      was to measure energy expenditure required to play repeated bouts of six
      Microsoft Xbox 360 Kinect games ("Motion Sports AdrenalineTM," "Sonic Free
      RidersTM," "Virtua Tennis 4TM," "Kinect SportsTM," "Kinect AdventuresTM," and
      "Just Dance 3TM"). SUBJECTS AND METHODS: Forty-seven children (between 10 and 15
      years) participated in a repeated-measures experiment, completing five 1-hour
      sessions (one familiarization and four separate gaming sessions). Three different
      AVGs were played for 15 minutes during each gaming session in a counterbalanced
      order. An Actiheart (CamNtech Ltd., Cambridge, United Kingdom) was used to
      monitor heart rate and acceleration during gameplay. RESULTS: Average energy
      expended across the six AVGs during 15 minutes of gameplay was 3.0+/-0.17
      metabolic equivalents/minute, significantly higher than resting energy
      expenditure (P<0.01). Similar levels of energy expenditure were observed between
      the first and fourth gaming session for all six games, although the energy
      expenditure between each game over the four sessions was similar. Boys expended
      more energy than girls within each AVG and across the four gaming sessions.
      CONCLUSIONS: The Microsoft Xbox 360 Kinect games in this study were found to
      elicit moderate-intensity exercise over four gaming sessions, with no decay in
      energy expenditure over several gaming sessions. Although small differences in
      the energy expenditure between the six Microsoft Xbox Kinect games were found,
      they are all likely to contribute toward reduced sitting time in children.

PMID- 26196929
TI  - A Machine Learning-Based Analysis of Game Data for Attention Deficit
      Hyperactivity Disorder Assessment.
AB  - OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is found in 9.5
      percent of the U.S. population and poses lifelong challenges. Current diagnostic
      approaches rely on evaluation forms completed by teachers and/or parents,
      although they are not specifically trained to recognize cognitive disorders. The
      most accurate diagnosis is by a psychiatrist, often only available to children
      with severe symptoms. Development of a tool that is engaging and objective and
      aids medical providers is needed in the diagnosis of ADHD. The goal of this
      research is to work toward the development of such a tool. MATERIALS AND METHODS:
      The proposed approach takes advantage of two trends: The rapid adoption of
      tangible user interface devices and the popularity of interactive videogames.
      CogCubed Inc. (Minneapolis, MN) has created "Groundskeeper," a game on the Sifteo
      Cubes (Sifteo, Inc., San Francisco, CA) game system with elements that exercise
      skills affected by ADHD. "Groundskeeper" was evaluated for 52 patients, with and
      without ADHD. Gameplay data were mathematically transformed into ADHD-indicative
      feature variables and subjected to machine learning algorithms to develop
      diagnostic models to aid psychiatric clinical assessments of ADHD. The
      effectiveness of the developed model was evaluated against the diagnostic
      impressions of two licensed child/adolescent psychiatrists using semistructured
      interviews. RESULTS: Our predictive algorithms were highly accurate in correctly
      predicting diagnoses based on gameplay of "Groundskeeper." The F-measure, a
      measure of diagnosis accuracy, from the predictive models gave values as follows:
      ADHD, inattentive type, 78 percent (P>0.05); ADHD, combined type, 75 percent
      (P<0.05); anxiety disorders, 71%; and depressive disorders, 76%. CONCLUSIONS:
      This represents a promising new approach to screening tools for ADHD.

PMID- 26196931
TI  - Serious Games for Healthcare: Applications and Implications.

PMID- 26196930
TI  - Comparing the Effects of a Novel and a Traditional Proprioceptive Balance
      Training Program on Activity Adherence and Balance Control in a Healthy
      University Population: A Preliminary Study.
AB  - OBJECTIVE: This study explored balance performance and participant adherence to
      either the Wii FitTM (Nintendo of America, Redmond, WA) or a proprioceptive
      BOSU((r)) (Ashland, OH) ball balance program. MATERIALS AND METHODS: Twenty
      university-aged participants were randomly allocated to either a Wii Fit or BOSU
      ball balance training program. Participants engaged in one of the two training
      regimens for 20 minutes, three times a week, for 4 weeks. Adherence was measured
      by recording attendance and time spent at each session. Motivational factors
      associated with adherence were assessed using the Physical Activity Enjoyment
      Scale. Balance was measured using a stabilometer. RESULTS: No significant
      difference in participant adherence was found between the groups. Significantly
      higher levels of activity enjoyment were reported from participants assigned to
      the Wii Fit intervention, and a positive correlation was found between physical
      activity enjoyment and adherence. A significant main effect for time
      demonstrating improved balance scores for both groups was found. No significant
      interaction between program type and time was found. DISCUSSION: Although both
      interventions led to balance improvements, Wii Fit participants reported
      significantly higher levels of activity enjoyment. Although these higher levels
      of enjoyment did not lead to a statistically significant difference between the
      groups with regard to the number of sessions attended, participants assigned to
      the Wii Fit group spent more time engaged in the balance training activities than
      those allocated to the BOSU group. Although this study is preliminary and has the
      limitations of being statistically underpowered and dissimilar from the
      unsupervised home-based programs often prescribed by health professionals,
      results suggest that exergaming-based balance training may be an important
      adjunct to traditional training programs.

PMID- 26196932
TI  - A new "off-on" fluorescent probe for Al(3+) in aqueous solution based on
      rhodamine B and its application to bioimaging.
AB  - In this paper, a new fluorescent probe has been synthesized and applied as "off
      on" sensor for the detection of Al(3+) with a high sensitivity and excellent
      selectivity in aqueous media. The sensor was easily prepared by one step reaction
      between rhodamine B hydrazide and pyridoxal hydrochloride named RBP. The
      structure of the sensor has been characterized by nuclear magnetic resonance and
      electron spray ionization-mass spectrometry. The fluorescence intensity and
      absorbance for the sensor showed a good linearity with the concentration of
      Al(3+) in the range of 0-12.5MUM and 8-44MUM, respectively, with detection limits
      of 0.23MUM and 1.90MUM. The sensor RBP was preliminarily applied to the
      determination of Al(3+) in water samples from the lake of Henan University and
      tap water with satisfying results. Moreover, it can be used as a bioimaging
      reagent for imaging of Al(3+) in living cells.

PMID- 26196933
TI  - Quenching of fluorescence in C60 fulleropyrrolidines by chloroform.
AB  - Functionalized [C60] fullerene, fulleropyrrolidines were synthesized and their
      photophysical properties are studied. The absorption and emission patterns are
      altered in fulleropyrrolidines, when compared with C60. Fluorescence of the
      molecules is quenched by CHCl3 in toluene solution at room temperature. Effect of
      nature and length of side chains in fulleropyrrolidine on quenching is
      investigated. Results suggested that the fluorescence intensity increased with
      increase in carbon chain length and the Stern-Volmer plot intercept values are
      indirectly proportional to the number of the carbons.

PMID- 26196934
TI  - Raman and infrared spectroscopy study on structure and microstructure of glass
      ceramic materials from SiO2-Al2O3-Na2O-K2O-CaO system modified by variable molar
      ratio of SiO2/Al2O3.
AB  - This paper is focused on the effect of the molar ratio of SiO2/Al2O3 on the
      microstructure and structure of the internal aluminium-silicon-oxide lattice of
      the glass-ceramic materials from the SiO2-Al2O3-Na2O-K2O-CaO system. In order to
      examine the real composition of the obtained samples, a chemical analysis was
      performed. Following the heat-treatment procedure, pseudowollastonite, anorthite
      and the vitreous phase were identified. In order to determine the microstructure,
      research using the scanning electron microscope (SEM) with EDS was done. For the
      inner structural study, X-ray diffraction (XRD), Raman spectroscopy as well as
      MIR and FIR spectroscopy were performed.

PMID- 26196935
TI  - The molecular structure and vibrational, (1)H and (13)C NMR spectra of lidocaine
      hydrochloride monohydrate.
AB  - The structure, vibrational and NMR spectra of the local anesthetic drug lidocaine
      hydrochloride monohydrate salt were investigated by B3LYP/6-311G(**)
      calculations. The lidocaine.HCl.H2O salt is predicted to have the gauche
      structure as the predominant form at ambient temperature with NCCN and CNCC
      torsional angles of 110 degrees  and -123 degrees  as compared to 10 degrees  and
      -64 degrees , respectively in the base lidocaine. The repulsive interaction
      between the two N-H bonds destabilized the gauche structure of lidocaine.HCl.H2O
      salt. The analysis of the observed vibrational spectra is consistent with the
      presence of the lidocaine salt in only one gauche conformation at room
      temperature. The (1)H and (13)C NMR spectra of lidocaine.HCl.H2O were interpreted
      by experimental and DFT calculated chemical shifts of the lidocaine salt. The
      RMSD between experimental and theoretical (1)H and (13)C chemical shifts for
      lidocaine.HCl.H2O is 2.32 and 8.21ppm, respectively.

PMID- 26196936
TI  - Experimental and theoretical study of urea and thiourea based new colorimetric
      chemosensor for fluoride and acetate ions.
AB  - Two new anion receptors 1,1-(4-nitro-1,2-phenylene) bis(3-phenylurea) (1) and 1,1
      (4-nitro-1,2-phenylene) bis(3-phenylthiourea) (2) have been reported here. The
      binding and colorimetric sensing properties of receptors 1 and 2 with different
      anions were investigated by naked-eye, (1)H-NMR and UV-Vis spectroscopy. They
      showed effective and selective binding with two biologically important anions F(
      ) and CH3COO(-), in presence of other anions, such as Cl(-), Br(-), I(-), NO2(-),
      ClO4(-), HSO4(-), H2PO4(-), N3(-), CN(-) in acetonitrile. The relative binding
      mode of fluoride and acetate anions towards receptors 1 and 2 were studied using
      density functional theory (DFT), in gas phase and in acetonitrile solvent.
      Computational studies revealed that receptor 1 formed complexes by two
      intermolecular hydrogen bonds while receptor 2 by three intermolecular hydrogen
      bonds. In addition, time dependent DFT (TD-DFT) calculations qualitatively match
      the experimental UV-Vis spectra.

PMID- 26196937
TI  - Enhanced red emission on co-doping of divalent ions (M(2+)=Ca(2+), Sr(2+),
      Ba(2+)) in YVO4:Eu(3+) phosphor and spectroscopic analysis for its application in
      display devices.
AB  - This paper reports the enhancement in photoluminescence due to the alkaline ions
      (M(2+)) co-doping in YVO4:Eu(3+) phosphors prepared by solid state reaction
      method. The as synthesized samples were found to have single phase tetragonal
      structure and the incorporation of dopant/codopant did not affect the crystal
      structure. The characteristic bands of YO and VO were located at 450cm(-1) and
      830cm(-1), respectively. The microscopic images exhibited the irregular
      morphology of the synthesized phosphor consisting of MUm sized particles. Upon UV
      excitations, all phosphors showed intense red-orange emissions corresponding to
      the (5)D0->(7)FJ=1,2:Eu(3+) transitions, and the emission intensity was further
      enhanced due to codoping. Divalent ions introduced radiative defect centers,
      which enhances the PL intensity significantly. The calculation of spectral
      parameters was done through Judd-Ofelt theory from emission spectra. The
      photometric characterizations and corresponding calculations indicated the
      suitability of the phosphor for display devices.

PMID- 26196938
TI  - Correction: An Assessment of the Methodological Quality of Published Network Meta
      Analyses: A Systematic Review.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0121715.]. 

PMID- 26196939
TI  - Profiling of primary metabolites and flavonols in leaves of two table grape
      varieties collected from semiarid and temperate regions.
AB  - Cultivation of grapes in West Bank - Palestine is very old and a large number of
      grape varieties exist as a result of continuous domestication over thousands of
      years. This rich biodiversity has highly influenced the consumer behavior of
      local people, who consume both grape berries and leaves. However, studies that
      address the contents of health-promoting metabolites in leaves are scarce.
      Accordingly the aim of this study is to assess metabolite levels in leaves of two
      grape varieties that were collected from semiarid and temperate regions.
      Metabolic profiling was conducted using GC-MS and LC-MS. The obtained results
      show that abiotic stresses in the semiarid region led to clear changes in primary
      metabolites, in particular in amino acids, which exist at very high levels. By
      contrast, qualitative and genotype-dependent differences in secondary metabolites
      were observed, whereas abiotic stresses appear to have negligible effect on the
      content of these metabolites. The qualitative difference in the flavonol profiles
      between the two genotypes is most probably related to differential expression of
      specific genes, in particular flavonol 3-O-rhamnosyltransferase, flavonol-3-O
      glycoside pentosyltransferases and flavonol-3-O-d-glucosidel-rhamnosyltransferase
      by 'Beituni' grape leaves, which led to much higher levels of flavonols with
      rutinoside, pentoside, and rhamnoside moieties with this genotype. 

PMID- 26196940
TI  - The broad spectrum 2-oxoglutarate oxygenase inhibitor N-oxalylglycine is present
      in rhubarb and spinach leaves.
AB  - 2-Oxoglutarate (2OG) and ferrous iron dependent oxygenases are involved in many
      biological processes in organisms ranging from humans (where some are therapeutic
      targets) to plants. These enzymes are of significant biomedicinal interest
      because of their roles in hypoxic signaling and epigenetic regulation. Synthetic
      N-oxalylglycine (NOG) has been identified as a broad-spectrum 2OG oxygenase
      inhibitor and is currently widely used in studies on the hypoxic response and
      chromatin modifications in animals. We report the identification of NOG as a
      natural product present in Rheum rhabarbarum (rhubarb) and Spinach oleracea
      (spinach) leaves; NOG was not observed in Escherchia coli or human embryonic
      kidney cells (HEK 293T). The finding presents the possibility that NOG plays a
      natural role in regulating gene expression by inhibiting 2OG dependent
      oxygenases. This has significance because tricarboxylic acid cycle (TCA)
      intermediate inhibition of 2OG dependent oxygenases has attracted major interest
      in cancer research. 

PMID- 26196941
TI  - Improvement of a Clinical Score for Necrotizing Fasciitis: 'Pain Out of
      Proportion' and High CRP Levels Aid the Diagnosis.
AB  - Necrotizing fasciitis (NF) is a rare mono-/polymicrobial skin infection that
      spreads to underlying tissues. NF is quickly progressing and leads to life
      threatening situations. Immediate surgical debridement together with i.v.
      antibiotic administration is required to avoid fatal outcome. Early diagnosis is
      often delayed due to underestimation or confusion with cellulitis. We now
      compared the initial clinical and laboratory presentation of NF and cellulitis in
      detail to assess if a typical pattern can be identified that aids timely
      diagnosis of NF and avoidance of fatal outcome. 138 different clinical and
      laboratory features of 29 NF patients were compared to those of 59 age- and
      gender matched patients with severe erysipelas requiring a subsequent
      hospitalization time of >=10 days. Differences in clinical presentation were not
      obvious; however, NF patients suffered significantly more often from strong pain.
      NF patients exhibited dramatically elevated CRP levels (5-fold, p>0.001). The
      overall laboratory risk indicator for necrotizing fasciitis (LRINEC) score was
      significantly higher in NF patients as compared to cellulitis. However, a
      modification of the score (alteration of laboratory parameters, addition of
      clinical parameters) led to a clear improvement of the score with a higher
      positive predictive value without losing specificity. In summary, clinical
      differentiation of NF from cellulitis appears to be hard. 'Pain out of
      proportion' may be an early sign for NF. An improvement of the LRINEC score
      emphasizing only relevant laboratory and clinical findings as suggested may aid
      the early diagnosis of NF in the future leading to improvement of disease outcome
      by enabling rapid adequate therapy.

PMID- 26196942
TI  - Diagnostic and Prognostic Values of Noninvasive Predictors of Portal Hypertension
      in Patients with Alcoholic Cirrhosis.
AB  - Portal hypertension is a direct consequence of hepatic fibrosis, and several
      hepatic fibrosis markers have been evaluated as a noninvasive alternative to the
      detection of portal hypertension and esophageal varices. In the present study, we
      compared the diagnostic and prognostic values of the noninvasive fibrosis markers
      in patients with alcoholic cirrhosis. A total of 219 consecutive alcoholic
      cirrhosis patients were included. Biochemical scores and liver stiffness (LS)
      were compared with hepatic venous pressure gradient (HVPG). For the detection of
      clinically significant portal hypertension (CSPH; HVPG>=10 mmHg) in compensated
      patients, LS and LS-spleen diameter to platelet ratio score (LSPS) showed
      significantly better performance with area under the curves (AUCs) of 0.85 and
      0.82, respectively, than aspartate aminotransferase-to-platelet ratio index, FIB
      4, Forns' index, Lok index, (platelet count)2/[monocyte fraction (%) * segmented
      neutrophil fraction (%)], and platelet count-to-spleen diameter ratio (all
      P<0.001). However, for the detection of high-risk varices, none of the non
      invasive tests showed reliable performance (AUCs of all investigated tests <
      0.70). During a median follow-up period of 42.6 months, 46 patients with
      decompensated cirrhosis died. Lok index (hazard ratio [HR], 1.13; 95% confidence
      interval [CI], 1.05-1.22; P = 0.001) and FIB-4 (HR, 1.06; 95% CI, 1.01-1.10; P =
      0.009) were independently associated with all-cause death in decompensated
      patients. Among the tested noninvasive markers, only Lok index significantly
      improved discrimination function of MELD score in predicting overall survival. In
      conclusion, LS and LSPS most accurately predict CSPH in patients with compensated
      alcoholic cirrhosis. In the prediction of overall survival in decompensated
      patients, however, Lok index is an independent prognostic factor and improves the
      predictive performance of MELD score. 

PMID- 26196944
TI  - Avian Gyrovirus 2 DNA in Fowl from Live Poultry Markets and in Healthy Humans,
      China.

PMID- 26196943
TI  - Protein phosphatase modulation of somatostatin receptor signaling in the mouse
      hippocampus.
AB  - Many inhibitory interneurones in the hippocampus release the neuropeptide
      somatostatin (SST) which inhibits neuronal excitability through Gi/Go-coupled
      receptors. To investigate the signaling pathways underlying the SST inhibition of
      neuronal excitability in the hippocampus, we performed perforated patch-clamp
      recordings from CA1 pyramidal neurones in acute brain slices from P14-P18 mice.
      Bath application of 1 MUM SST reversibly reduces the frequency of action
      potential firing in response to depolarising current steps, and is associated
      with neuronal hyperpolarisation and a reduction in membrane resistance. This
      effect is mediated by potassium channels with KCNK-like pharmacology. In
      addition, in slices that have been cultured in vitro for seven days or more, SST
      also produces a hyperpolarisation independent reduction in action potential
      firing, which can be also observed in acute slices when the Ser/Thr protein
      phosphatases PP2A and PP4 are inhibited selectively with fostriecin. This
      hyperpolarisation independent effect of SST appears to be mediated by G-protein
      activated inwardly rectifying K+ (GIRK) channels. Knockdown of protein
      phosphatase 5, by Cre recombinase mediated deletion of the floxed Ppp5c gene,
      blocks the hyperpolarisation independent effect of SST, and reduces the
      hyperpolarisation dependent effect in a manner consistent with increased SST
      receptor desensitisation. Thus, reversible protein phosphorylation provides a
      mechanism to enhance or diminish the inhibitory effect of SST, which could allow
      system level regulation of circuit excitability in the hippocampus.

PMID- 26196945
TI  - Evaluation of dementia by acrolein, amyloid-beta and creatinine.
AB  - Plasma, urine and cerebrospinal fluid (CSF) were examined for biochemical markers
      of dementia. Protein-conjugated acrolein (PC-Acro) and the amyloid-beta
      (Abeta)40/42 ratio in plasma can be used to detect mild cognitive impairment
      (MCI) and Alzheimer's disease (AD). In plasma, PC-Acro and the Abeta40/42 ratio
      in MCI and AD were significantly higher relative to non-demented subjects.
      Furthermore, urine acrolein metabolite, 3-hydroxypropyl mercapturic acid (3
      HPMA)/creatinine (Cre) and amino acid-conjugated acrolein (AC-Acro)/Cre in AD
      were significantly lower than MCI. It was also shown that reduced urine 3
      HPMA/Cre correlated with increased plasma Abeta40/42 ratio in dementia. The
      Abeta40/PC-Acro ratio in CSF, together with Abeta40 and Abeta40/42 ratio, was
      lower in AD than MCI. Increased plasma PC-Acro and Abeta40/42 ratio and decreased
      urine 3-HPMA/Cre correlated with cognitive ability (MMSE). These results indicate
      that the measurements of acrolein derivatives together with Abeta and Cre in
      biologic fluids is useful to estimate severity of dementia. 

PMID- 26196946
TI  - Poly(ADP-ribosylation) and neurodegenerative disorders.
AB  - Impaired mitochondrial structure and function are common features of
      neurodegenerative disorders, ultimately characterized by the death of neural
      cells promoted by still unknown signals. Among the possible modulators of
      neurodegeneration, the activation of poly(ADP-ribosylation), a post-translational
      modification of proteins, has been considered, being the product of the reaction,
      poly(ADP-ribose), a signaling molecule for different cell death paradigms. The
      basic properties of poly(ADP-ribosylation) are here described, focusing on the
      mitochondrial events; cell death paradigms such as apoptosis, parthanatos,
      necroptosis and mitophagy are illustrated. Finally, the promising use of poly(ADP
      ribosylation) inhibitors to rescue neurodegeneration is addressed. 

PMID- 26196947
TI  - BTK: sensing pathogenic nucleic acids.

PMID- 26196948
TI  - Serum Immunoproteomics Combined With Pathological Reassessment of Surgical
      Specimens Identifies TCP-1zeta Autoantibody as a Potential Biomarker in Thyroid
      Neoplasia.
AB  - CONTEXT: Current methods of preoperative diagnostics frequently fail to
      discriminate between benign and malignant thyroid neoplasms. In encapsulated
      follicular-patterned tumors (EnFPT), this discrimination is challenging even
      using histopathological analysis. Autoantibody response against tumor-associated
      antigens is a well-documented phenomenon with prominent diagnostic potential;
      however, autoantigenicity of thyroid tumors remains poorly explored. OBJECTIVES:
      Objectives were exploration of tumor-associated antigen repertoire of thyroid
      tumors and identification of candidate autoantibody biomarkers capable of
      discrimination between benign and malignant thyroid neoplasms. DESIGN, SETTING,
      AND PATIENTS: Proteins isolated from FTC-133 cells were subjected to two
      dimensional Western blotting using pooled serum samples of patients originally
      diagnosed with either papillary thyroid carcinoma (PTC) or EnFPT represented by
      apparently benign follicular thyroid adenomas, as well as healthy individuals.
      Immunoreactive proteins were identified using liquid chromatography-tandem mass
      spectrometry. Pathological reassessment of EnFPT was performed applying
      nonconservative criteria for capsular invasion and significance of focal PTC
      nuclear changes (PTC-NCs). Recombinant T-complex protein 1 subunitzeta (TCP
      1zeta) was used to examine an expanded serum sample set of patients with various
      thyroid neoplasms (n = 89) for TCP-1zeta autoantibodies. All patients were
      included in tertiary referral centers. RESULTS: A protein demonstrating a
      distinct pattern of EnFPT-specific seroreactivity was identified as TCP-1zeta
      protein. A subsequent search for clinicopathological correlates of TCP-1zeta
      seroreactivity revealed nonclassical capsular invasion or focal PTC-NC in all TCP
      1zeta antibody-positive cases. Further studies in an expanded sample set
      confirmed the specificity of TCP-1zeta autoantibodies to malignant EnFPT.
      CONCLUSIONS: We identified TCP-1zeta autoantibodies as a potential biomarker for
      presurgical discrimination between benign and malignant encapsulated follicular
      patterned thyroid tumors. Our results suggest the use of nonconservative
      morphological criteria for diagnosis of malignant EnFPT in biomarker
      identification studies and provide a peculiar example of uncovering the
      diagnostic potential of a candidate biomarker using incorporation of pathological
      reassessment in the pipeline of immunoproteomic research.

PMID- 26196949
TI  - PTH(1-34) for Surgical Hypoparathyroidism: A Prospective, Open-Label
      Investigation of Efficacy and Quality of Life.
AB  - CONTEXT: Conventional therapy for hypoparathyroidism consists of calcium and
      calcitriol, but sometimes normal serum calcium cannot be maintained, and/or this
      approach might lead to nephrocalcinosis, nephrolithiasis, or renal insufficiency.
      OBJECTIVE: The objective of the study was to investigate the effects of 6 months
      of PTH(1-34) treatment in adult subjects with postoperative hypoparathyroidism
      and to evaluate quality-of-life changes. DESIGN: This was a 2-year prospective,
      open-label study. At baseline and after 6 months of PTH(1-34) treatment, calcium
      and vitamin D supplementation requirements, serum calcium, phosphate, creatinine,
      alkaline phosphatase, uric acid, and 24-hour urinary calcium excretion were
      evaluated. Quality of life was evaluated by the Rand 36-Item Short Form Health
      Survey covering eight domains of physical and mental health. SETTING: This was an
      Italian multicentric study. PARTICIPANTS: Participants included 42 subjects with
      surgical hypoparathyroidism (90% females, age range 34-77 y). INTERVENTION: The
      intervention included a twice-daily PTH(1-34) 20 MUg sc injection. RESULTS: The
      mean serum calcium levels significantly increased from baseline to 15 days (7.6
      +/- 0.6 vs 9.1 +/- 0.9 mg/dL, P < .001) and remained stable until the end of the
      observational period, despite a significant reduction in calcium and vitamin D
      supplementation. Phosphate levels gradually decreased from baseline to the sixth
      month (P = .005 for the trend), whereas the alkaline phosphatase increased (P <
      .001). Data from the Rand 36-Item Short Form Health Survey showed a significant
      improvement in the mean scores of all eight domains (P < .001). CONCLUSION: This
      is the largest study that demonstrates the effectiveness of PTH(1-34) in the
      treatment of adult patients with postsurgical hypoparathyroidism, and it shows
      that PTH(1-34) may improve the mental and physical health in hypoparathyroid
      subjects.

PMID- 26196950
TI  - Accuracy of Late-Night Salivary Cortisol in Evaluating Postoperative Remission
      and Recurrence in Cushing's Disease.
AB  - CONTEXT: Late-night salivary cortisol (LNSC) is well-validated in the diagnosis
      of Cushing's disease (CD). The accuracy of LNSC during follow-up of patients
      undergoing transsphenoidal surgery (TSS) has not been fully characterized.
      OBJECTIVES: We examined the accuracy of LNSC in establishing remission and
      identifying recurrence in postoperative patients with CD. DESIGN: This is a
      retrospective study. PATIENTS: Records of patients with CD who underwent TSS by a
      single neurosurgeon in our tertiary center (2005-2014) were analyzed (N = 224).
      Patients were selected for further investigation (n = 165) if there was at least
      one available LNSC test obtained after TSS (either within 3 months or during long
      term follow-up). Extracted data included demographic and clinical
      characteristics, magnetic resonance imaging and laboratory data (morning serum
      cortisol, 24-hour urine free cortisol [UFC], LNSC) . MAIN OUTCOMES AND MEASURES:
      Remission was defined as nadir morning serum cortisol less than 5 mcg/dl and
      nadir 24-hour UFC less than 23 mcg. Recurrence was considered definite if
      confirmed surgically or prompted radiotherapy. RESULTS: Surgical remission
      occurred in 89% of 89 patients with available LNSC data. LNSC, obtained within 3
      months of TSS, established remission with 94% sensitivity and 80% specificity at
      a cutpoint of 1.9 nmol/l (area under the curve [AUC] = 0.90). At a median follow
      up of 53.5 months, LNSC established recurrence (75% sensitivity and 95%
      specificity) at a cutpoint of 7.4 nmol/l (AUC = 0.87), and 24-hour UFC
      established recurrence (68% sensitivity and 100% specificity) at a cutpoint of
      1.6-fold above normal (AUC = 0.82). CONCLUSIONS: LNSC may accurately establish
      remission after TSS and identify recurrence more accurately than 24-hour UFC
      during long-term follow-up.

PMID- 26196951
TI  - Vitamin D Associations With Renal, Bone, and Cardiovascular Phenotypes: African
      American-Diabetes Heart Study.
AB  - CONTEXT: Vitamin D binding protein (DBP) is an important determinant of
      bioavailable vitamin D (BAVD) and may provide clues to racial variation in
      osteoporosis and atherosclerosis. OBJECTIVE: The objective was to assess
      relationships between DBP, BAVD, 25-hydroxyvitamin D (25OHD), and 1,25 di
      hydroxyvitamin D (1,25OH2D) with kidney, bone, adipose, and atherosclerosis
      phenotypes in African Americans with type 2 diabetes. DESIGN: Cross-sectional (N
      = 545) and longitudinal (N = 288; mean 5.1 +/- 0.9-year follow-up) relationships
      between vitamin D concentrations with renal phenotypes, vertebral bone mineral
      density, aorto-iliac, coronary artery, and carotid artery calcified plaque (CP),
      and adipose tissue volumes were studied. SETTING: African American-Diabetes Heart
      Study. PATIENTS: Participants were 56.7% female with mean +/- standard deviation
      (sd) age 55.6 +/- 9.6 years, diabetes duration 10.3 +/- 8.2 years, and eGFR 90.9
      +/- 22.1 ml/min/1.73 m(2). INTERVENTIONS: None. MAIN OUTCOMES AND MEASURES:
      Associations tested between vitamin D and the previously mentioned phenotypes
      adjusting for age, sex, African ancestry proportion, diabetes duration, statins,
      smoking, changes in estimated glomerular filtration rate, body mass index,
      hemoglobin A1c, and blood pressure. RESULTS: 1,25OH2D was inversely associated
      with change in coronary artery CP (parameter estimate [beta] -0.005, standard
      error [SE] 0.002; P = .037), with a trend for change in carotid artery CP (beta 
      0.007, SE 0.004; P = .074). Further adjustment for renin-aldosterone-system
      blockade revealed inverse association between 1,25OH2D and change in albuminuria
      (beta -0.004, SE 0.002; P = .037). DBP, BAVD, and 25OHD did not associate
      significantly with changes in albuminuria, CP, or bone mineral density. BAVD was
      inversely associated with visceral, subcutaneous, intermuscular, and pericardial
      adipose volumes. CONCLUSIONS: In contrast to BAVD and 25OHD, only 1,25OH2D levels
      were significantly and inversely associated with changes in subclinical
      atherosclerosis and albuminuria in African Americans, suggesting potential
      beneficial effects.

PMID- 26196953
TI  - On the fate of non-cued mental representations in visuo-spatial working memory:
      Evidence by a retro-cuing paradigm.
AB  - By means of a visual retro-cuing paradigm, we investigated the influence of
      working memory representations that are not required for an ongoing task. A retro
      cue reliably indicated the items on the left or right side of a memory array that
      remained relevant for a subsequent recognition task. On ERP level, the
      attentional selection of cued memory contents was reflected by a contralateral
      negativity that appeared at temporal sites in an interval following retro-cue
      presentation (i.e., 200-400ms). Additionally, the retro-cue caused a suppression
      of posterior induced alpha power contralateral to the relevant memory items
      reflecting the release of non-cued information from active maintenance in visuo
      spatial working memory. Following the retro-cue, a central probe item was
      presented and participants had to state whether this stimulus was previously
      shown on the relevant side of the memory array. The probe was either a cued
      memory item (cued probe), non-cued memory item (non-cued probe) or was not shown
      in the previous memory array (new probe). While the same response was required,
      the non-cued probe condition featured slower response times referred to the new
      probe condition. In line with these results, a comparison of the probe-locked
      ERPs pointed toward additional memory retrieval and conflict control mechanisms
      when processing non-cued probes compared to new probes. Thus although retro-cues
      were used to drop non-cued information from working memory, it still interfered
      with the processing of new sensory information based on residual spatial
      representations in a passive and fragile short-term memory store. 

PMID- 26196952
TI  - Early Increases in Bile Acids Post Roux-en-Y Gastric Bypass Are Driven by Insulin
      Sensitizing, Secondary Bile Acids.
AB  - CONTEXT: Roux-en-Y gastric bypass (RYGB) is the most effective treatment for
      morbid obesity and resolution of diabetes. Over the last decade, it has become
      well accepted that this resolution of diabetes occurs before significant weight
      loss; however, the mechanisms behind this effect remain unknown and could
      represent novel therapeutic targets for obesity and diabetes. Bile acids have
      been identified as putative mediators of these weight loss-independent effects.
      OBJECTIVE: To identify the longitudinal changes in bile acids after RYGB, which
      may provide mechanistic insight into the weight loss-independent effects of RYGB.
      DESIGN: Observational study before/after intervention. SETTING: Academic medical
      center. PATIENTS/PARTICIPANTS: Samples were collected from morbidly obese
      patients (n = 21) before and after RYGB. INTERVENTION: RYGB. MAIN OUTCOME
      MEASURES: Seventeen individual bile acid species were measured preoperatively and
      at 1, 6, 12, and 24 months postoperatively. Anthropometric, hormonal, and
      hyperinsulinemic-euglycemic clamp data were also examined to identify
      physiological parameters associated with bile acid changes. RESULTS: Fasting
      total plasma bile acids increased after RYGB; however, increases were bimodal and
      were observed only at 1 (P < .05) and 24 months (P < .01). One-month increases
      were secondary to surges in ursodeoxycholic acid and its glycine and taurine
      conjugates, bacterially derived bile acids with putative insulin-sensitizing
      effects. Increases at 24 months were due to gradual rises in primary unconjugated
      bile acids as well as deoxycholic acid and its glycine conjugate. Plasma bile
      acid changes were not significantly associated with any anthropometric or
      hormonal measures, although hepatic insulin sensitivity was significantly
      improved at 1 month. CONCLUSIONS: Overall findings suggest that bacterially
      derived bile acids may mediate the early improvements at 1 month after RYGB.
      Future studies should examine the changes in specific bile acid chemical species
      after bariatric procedures and bile acid-specific signaling changes.

PMID- 26196954
TI  - An animal model of disengagement: Temporary inactivation of the superior
      colliculus impairs attention disengagement in rats.
AB  - The orienting attention network is responsible for prioritizing sensory input
      through overt or covert shifts of attention among targets. The ability to
      disengage attention is essential for the proper functioning of this network. In
      addition to its importance for proper orienting, deficits in disengagement have
      been recently implicated in autism disorders. Despite its importance, the neural
      mechanisms underlying disengagement processing are still poorly understood. In
      this study, the involvement of the superior colliculus (SC) in disengagement was
      investigated in unrestrained rats that had been trained in a two-alternative
      light-guided spatial choice task. At each trial, the rats had to choose one of
      two paths, leading either to a large or a small reward, based on 1 (single-cue)
      or 2 (double-cue) lights. The task consisted of serial trials with single- and/or
      double-cue lights, and rats could acquire a large reward if the rats chose
      infrequent lights when infrequent cue lights were presented after preceding
      frequent cue lights. Experiment 1 included trials with either single- or double
      cue lights, and infrequent trials with double-cue lights required both
      attentional disengagement and shift of attention from preceding frequent single
      cue lights, while experiment 2 included only trials with single-cue lights
      requiring shifts of attention but not attentional disengagement. The results
      indicated that temporary inactivation of the SC by muscimol injections
      selectively impaired performance on trials requiring disengagement. No impairment
      was observed on the other trials, in which attention disengagement was not
      required. The results provide the first evidence that the SC is necessary for
      attentional disengagement. 

PMID- 26196955
TI  - Differentiation of Acute Q Fever from Other Infections in Patients Presenting to
      Hospitals, the Netherlands
AB  - Differentiating acute Q fever from infections caused by other pathogens is
      essential. We conducted a retrospective case-control study to evaluate
      differences in clinical signs, symptoms, and outcomes for 82 patients with acute
      Q fever and 52 control patients who had pneumonia, fever and lower respiratory
      tract symptoms, or fever and hepatitis, but had negative serologic results for Q
      fever. Patients with acute Q fever were younger and had higher C-reactive protein
      levels but lower leukocyte counts. However, a large overlap was found. In
      patients with an indication for prophylaxis, chronic Q fever did not develop
      after patients received prophylaxis but did develop in 50% of patients who did
      not receive prophylaxis. Differentiating acute Q fever from other respiratory
      infections, fever, or hepatitis is not possible without serologic testing or PCR.
      If risk factors for chronic Q fever are present, prophylactic treatment is
      advised.

PMID- 26196956
TI  - The Spatial Pattern and Interactions of Woody Plants on the Temperate Savanna of
      Inner Mongolia, China: The Effects of Alternating Seasonal Grazing-Mowing
      Regimes.
AB  - Ulmus pumila tree-dominated temperate savanna, which is distributed widely
      throughout the forest-steppe ecotone on the Mongolian Plateau, is a relatively
      stable woody-herbaceous complex ecosystem in northern China. Relatively more
      attention has been paid to the degradation of typical steppe areas, whereas less
      focus has been placed on the succession of this typical temperate savanna under
      the present management regime. In this study, we established 3 sample plots 100
      m*100 m in size along a gradient of fixed distances from one herder's stationary
      site and then surveyed all the woody plants in these plots. A spatial point
      pattern analysis was employed to clarify the spatial distribution and interaction
      of these woody plants. The results indicated that old U. pumila trees (DBH >= 20
      cm) showed a random distribution and that medium U. pumila trees (5 cm <= DBH <
      20 cm) showed an aggregated distribution at a smaller scale and a random
      distribution at a larger scale; few or no juvenile trees (DBH < 5 cm) were
      present, and seedlings (without DBH) formed aggregations in all 3 plots. These
      findings can be explained by an alternate seasonal grazing-mowing regime
      (exclosure in summer, mowing in autumn and grazing in winter and spring); the
      shrubs in all 3 plots exist along a grazing gradient that harbors xerophytic and
      mesophytic shrubs. Of these shrubs, xerophytic shrubs show significant
      aggregation at a smaller scale (0-5.5 m), whereas mesophytic shrubs show
      significant aggregation at a larger scale (0-25 m), which may be the result of
      the dual effects of grazing pressure and climate change. Medium trees and
      seedlings significantly facilitate the distributions of xerophytic shrubs and
      compete significantly with mesophytic shrubs due to differences in water use
      strategies. We conclude that the implementation of an alternative grazing-mowing
      regime results in xerophytic shrub encroachment or existence, breaking the chain
      of normal succession in a U. pumila tree community in this typical temperate
      savanna ecosystem. This might eventually result in the degradation of the
      original tree-dominated savanna to a xerophytic shrub-dominated savanna.

PMID- 26196958
TI  - Scanning Probe Characterization of Heterostructured Colloidal Nanomaterials.

PMID- 26196957
TI  - Suppression of Poly(rC)-Binding Protein 4 (PCBP4) reduced cisplatin resistance in
      human maxillary cancer cells.
AB  - Cisplatin plays an important role in the therapy for human head and neck cancers.
      However, cancer cells develop cisplatin resistance, leading to difficulty in
      treatment and poor prognosis. To analyze cisplatin-resistant mechanisms, a
      cisplatin-resistant cell line, IMC-3CR, was established from the IMC-3 human
      maxillary cancer cell line. Flow cytometry revealed that, compared with IMC-3
      cells, cisplatin more dominantly induced cell cycle G2/M arrest rather than
      apoptosis in IMC-3CR cells. That fact suggests that IMC-3CR cells avoid cisplatin
      induced apoptosis through induction of G2/M arrest, which allows cancer cells to
      repair damaged DNA and survive. In the present study, we specifically examined
      Poly(rC)-Binding Protein 4 (PCBP4), which reportedly induces G2/M arrest. Results
      showed that suppression of PCBP4 by RNAi reduced cisplatin-induced G2/M arrest
      and enhanced apoptosis in IMC-3CR cells, resulting in the reduction of cisplatin
      resistance. In contrast, overexpression of PCBP4 in IMC-3 cells induced G2/M
      arrest after cisplatin treatment and enhanced cisplatin resistance. We revealed
      that PCBP4 combined with Cdc25A and suppressed the expression of Cdc25A,
      resulting in G2/M arrest. PCBP4 plays important roles in the induction of
      cisplatin resistance in human maxillary cancers. PCBP4 is a novel molecular
      target for the therapy of head and neck cancers, especially cisplatin-resistant
      cancers. 

PMID- 26196959
TI  - Correction to "Oxidative Substitution of Boranephosphonate Diesters as a Route to
      Post-synthetically Modified DNA".

PMID- 26196960
TI  - Tuning up STAT1.

PMID- 26196961
TI  - Planned caesarean section for term breech delivery.
AB  - BACKGROUND: Poor outcomes after breech birth might be the result of underlying
      conditions causing breech presentation or due to factors associated with the
      delivery. OBJECTIVES: To assess the effects of planned caesarean section for
      singleton breech presentation at term on measures of pregnancy outcome. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (31 March 2015). SELECTION CRITERIA: Randomised trials comparing planned
      caesarean section for singleton breech presentation at term with planned vaginal
      birth. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed
      trials for inclusion and risk of bias, extracted data and checked them for
      accuracy. MAIN RESULTS: Three trials (2396 participants) were included in the
      review. Caesarean delivery occurred in 550/1227 (45%) of those women allocated to
      a vaginal delivery protocol and 1060/1169 (91%) of those women allocated to
      planned caesarean section (average risk ratio (RR) random-effects, 1.88, 95%
      confidence interval (CI) 1.60 to 2.20; three studies, 2396 women, evidence graded
      low quality). Perinatal or neonatal death (excluding fatal anomalies) or severe
      neonatal morbidity was reduced with a policy of planned caesarean section in
      settings with a low national perinatal mortality rate (RR 0.07, 95% CI 0.02 to
      0.29, one study, 1025 women, evidence graded moderate quality), but not in
      settings with a high national perinatal mortality rate (RR 0.66, 95% CI 0.35 to
      1.24, one study, 1053 women, evidence graded low quality). The difference between
      subgroups was significant (Test for subgroup differences: Chi2 = 8.01, df = 1 (P
      = 0.005), I2 = 87.5%). Due to this significant heterogeneity, a random-effects
      analysis was performed. The average overall effect was not statistically
      significant (RR 0.23, 95% CI 0.02 to 2.44, one study, 2078 infants). Perinatal or
      neonatal death (excluding fatal anomalies) was reduced with planned caesarean
      section (RR 0.29, 95% CI 0.10 to 0.86, three studies, 2388 women). The
      proportional reductions were similar for countries with low and high national
      perinatal mortality rates.The numbers studied were too small to satisfactorily
      address reductions in birth trauma and brachial plexus injury with planned
      caesarean section. Neither of these outcomes reached statistical significance
      (birth trauma: RR 0.42, 95% CI 0.16 to 1.10, one study, 2062 infants (20
      events),evidence graded low quality; brachial plexus injury: RR 0.35, 95% CI 0.08
      to 1.47, three studies, 2375 infants (nine events)).Planned caesarean section was
      associated with modestly increased short-term maternal morbidity (RR 1.29, 95% CI
      1.03 to 1.61, three studies, 2396 women,low quality evidence). At three months
      after delivery, women allocated to the planned caesarean section group reported
      less urinary incontinence (RR 0.62, 95% CI 0.41 to 0.93, one study, 1595 women);
      no difference in 'any pain' (RR 1.09, 95% CI 0.93 to 1.29, one study, 1593
      women,low quality evidence); more abdominal pain (RR 1.89, 95% CI 1.29 to 2.79,
      one study, 1593 women); and less perineal pain (RR 0.32, 95% CI 0.18 to 0.58, one
      study, 1593 women).At two years, there were no differences in the combined
      outcome 'death or neurodevelopmental delay' (RR 1.09, 95% CI 0.52 to 2.30, one
      study, 920 children,evidence graded low quality); more infants who had been
      allocated to planned caesarean delivery had medical problems at two years (RR
      1.41, 95% CI 1.05 to 1.89, one study, 843 children). Maternal outcomes at two
      years were also similar. In countries with low perinatal mortality rates, the
      protocol of planned caesarean section was associated with lower healthcare costs,
      expressed in 2002 Canadian dollars (mean difference -$877.00, 95% CI -894.89 to 
      859.11, one study, 1027 women).All of the trials included in this review had
      design limitations, and the GRADE level of evidence was mostly low. No studies
      attempted to blind the intervention, and the process of random allocation was
      suboptimal in two studies. Two of the three trials had serious design
      limitations, however these studies contributed to fewer outcomes than the large
      multi-centre trial with lower risk of bias. AUTHORS' CONCLUSIONS: Planned
      caesarean section compared with planned vaginal birth reduced perinatal or
      neonatal death as well as the composite outcome death or serious neonatal
      morbidity, at the expense of somewhat increased maternal morbidity. In a subset
      with 2-year follow up, infant medical problems were increased following planned
      caesarean section and no difference in long-term neurodevelopmental delay or the
      outcome "death or neurodevelopmental delay" was found, though the numbers were
      too small to exclude the possibility of an important difference in either
      direction.The benefits need to be weighed against factors such as the mother's
      preference for vaginal birth and risks such as future pregnancy complications in
      the woman's specific healthcare setting. The option of external cephalic version
      is dealt with in separate reviews. The data from this review cannot be
      generalised to settings where caesarean section is not readily available, or to
      methods of breech delivery that differ materially from the clinical delivery
      protocols used in the trials reviewed. The review will help to inform
      individualised decision-making regarding breech delivery. Research on strategies
      to improve the safety of breech delivery and to further investigate the possible
      association of caesarean section with infant medical problems is needed.

PMID- 26196963
TI  - ITG: A New Global GNSS Tropospheric Correction Model.
AB  - Tropospheric correction models are receiving increasing attentions, as they play
      a crucial role in Global Navigation Satellite System (GNSS). Most commonly used
      models to date include the GPT2 series and the TropGrid2. In this study, we
      analyzed the advantages and disadvantages of existing models and developed a new
      model called the Improved Tropospheric Grid (ITG). ITG considers annual, semi
      annual and diurnal variations, and includes multiple tropospheric parameters. The
      amplitude and initial phase of diurnal variation are estimated as a periodic
      function. ITG provides temperature, pressure, the weighted mean temperature (Tm)
      and Zenith Wet Delay (ZWD). We conducted a performance comparison among the
      proposed ITG model and previous ones, in terms of meteorological measurements
      from 698 observation stations, Zenith Total Delay (ZTD) products from 280
      International GNSS Service (IGS) station and Tm from Global Geodetic Observing
      System (GGOS) products. Results indicate that ITG offers the best performance on
      the whole. 

PMID- 26196962
TI  - A potent broad-spectrum protective human monoclonal antibody crosslinking two
      haemagglutinin monomers of influenza A virus.
AB  - Effective annual influenza vaccination requires frequent changes in vaccine
      composition due to both antigenic shift for different subtype hemagglutinins
      (HAs) and antigenic drift in a particular HA. Here we present a broadly
      neutralizing human monoclonal antibody with an unusual binding modality. The
      antibody, designated CT149, was isolated from convalescent patients infected with
      pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some
      group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane
      fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent
      cellular cytotoxicity and complement-dependent cytotoxicity. X-ray
      crystallographic data reveal that CT149 binds primarily to the fusion domain in
      HA2, and the light chain is also largely involved in binding. The epitope
      recognized by this antibody comprises amino-acid residues from two adjacent
      protomers of HA. This binding characteristic of CT149 will provide more
      information to support the design of more potent influenza vaccines. 

PMID- 26196964
TI  - Birth order, sibship size, and status in modern Canada.
AB  - This paper investigates the possibility that birth order affects the degree to
      which individuals attain higher status. Humans give birth to a variable number of
      (usually) single offspring spaced one to many years apart, and continue to
      maintain contact with them for extended periods of time. The continued presence
      of older siblings, and arrival of younger ones, means that each child is reared
      in a different family environment. Research findings from the field of behavior
      genetics suggest that these differences have a significant impact on the
      development of individual differences between children in the same family.
      Although no two families are likely to be exactly the same, factors such as birth
      order remain constant across them, and may have similar influences. The present
      study examines the relationships between birth order, sibship size, and several
      variables thought to index future status attainment (status striving) in a random
      sample of Canadians. Firstborn children appear to be more status oriented than
      lastborns, and this effect is mediated by sibship size. While firstborn children
      are unaffected by the number of younger siblings they have, the status ambitions
      of youngest children decrease the more older siblings they have. Birth order
      effects on status attainment are not as strong as they are on status ambitions. 

PMID- 26196965
TI  - Human conversational behavior.
AB  - Observational studies of human conversations in relaxed social settings suggest
      that these consist predominantly of exchanges of social information (mostly
      concerning personal relationships and experiences). Most of these exchanges
      involve information about the speaker or third parties, and very few involve
      critical comments or the soliciting or giving of advice. Although a policing
      function may still be important (e.g., for controlling social cheats), it seems
      that this does not often involve overt criticism of other individuals' behavior.
      The few significant differences between the sexes in the proportion of
      conversation time devoted to particular topics are interpreted as reflecting
      females' concerns with networking and males' concerns with self-display in what
      amount to a conventional mating lek. 

PMID- 26196966
TI  - A reexamination of Gilligan's analysis of the female moral system : Distaff
      altruism will not succeed.
AB  - Gilligan's (1982) refinement of Kohlberg's theory on moral development operates
      on two theses: (1) females, more so than males, reach moral decisions based on
      the personalities of the relevant individuals; and (2) female behaviors stemming
      from moral decisions are based upon "care" and "responsibility for others." This
      article accepts the first thesis but argues that the second is incorrect. That
      is, self-interest-i.e., aiding "blood" kin and/or carefully monitoring
      reciprocity-rather than "altruism" is argued to be the operant dynamic in forging
      distaff morality and resultant behavior. Six empirical examples are presented as
      contraindicative of Gilligan's second thesis. Finally, it is suggested that
      selection for the psychological traits of independence and the mastery of subtle
      social chess yielded ancestral females who had more descendants-us-than did
      females with alternative profiles. 

PMID- 26196967
TI  - Differential use of sensory information in sexual behavior as a function of
      gender.
AB  - Olfactory information is critical to mammalian sexual behavior. Based on parental
      investment theory the relative importance of olfaction compared with vision,
      touch, and hearing should be different for human males and females. In
      particular, because of its link to immunological profile and offspring viability,
      odor should be a more important determinant of sexual choice and arousal for
      females than for males. To test this hypothesis a questionnaire was developed and
      administered to 332 adults (166 males, 166 females). Subjects used a 1-7 scale to
      indicate how much they agreed with a series of statements concerning the
      importance of olfactory, visual, auditory, and tactile information for their
      sexual responsivity. The data reveal that males rated visual and olfactory
      information as being equally important for selecting a lover, while females
      considered olfactory information to be the single most important variable in mate
      choice. Additionally, when considering sexual activity, females singled out body
      odor from all other sensory experiences as most able to negatively affect desire,
      while males regarded odors as much more neutral stimuli for sexual arousal. The
      present results support recent findings in mice and humans concerning the
      relation of female preferences in body odor and major histocompatibility complex
      (MHC) compatibility and can be explained by an evolutionary analysis of sex
      differences in reproductive strategies. This work represents the first direct
      examination of the role of different forms of sensory information in human sexual
      behavior. 

PMID- 26196968
TI  - Accurate and Robust Unitary Transformations of a High-Dimensional Quantum System.
AB  - Unitary transformations are the most general input-output maps available in
      closed quantum systems. Good control protocols have been developed for qubits,
      but questions remain about the use of optimal control theory to design unitary
      maps in high-dimensional Hilbert spaces, and about the feasibility of their
      robust implementation in the laboratory. Here we design and implement unitary
      maps in a 16-dimensional Hilbert space associated with the 6S(1/2) ground state
      of (133)Cs, achieving fidelities >0.98 with built-in robustness to static and
      dynamic perturbations. Our work has relevance for quantum information processing
      and provides a template for similar advances on other physical platforms.

PMID- 26196969
TI  - Thermal and Residual Excited-State Population in a 3D Transmon Qubit.
AB  - Remarkable advancements in coherence and control fidelity have been achieved in
      recent years with cryogenic solid-state qubits. Nonetheless, thermalizing such
      devices to their milliKelvin environments has remained a long-standing
      fundamental and technical challenge. In this context, we present a systematic
      study of the first-excited-state population in a 3D transmon superconducting
      qubit mounted in a dilution refrigerator with a variable temperature. Using a
      modified version of the protocol developed by Geerlings et al., we observe the
      excited-state population to be consistent with a Maxwell-Boltzmann distribution,
      i.e., a qubit in thermal equilibrium with the refrigerator, over the temperature
      range 35-150 mK. Below 35 mK, the excited-state population saturates at
      approximately 0.1%. We verified this result using a flux qubit with ten times
      stronger coupling to its readout resonator. We conclude that these qubits have
      effective temperature T(eff)=35  mK. Assuming T(eff) is due solely to hot
      quasiparticles, the inferred qubit lifetime is 108  MUs and in plausible
      agreement with the measured 80  MUs.

PMID- 26196970
TI  - Particle Dark Matter Searches Outside the Local Group.
AB  - If dark matter (DM) is composed by particles which are nongravitationally coupled
      to ordinary matter, their annihilations or decays in cosmic structures can result
      in detectable radiation. We show that the most powerful technique to detect a
      particle DM signal outside the Local Group is to study the angular cross
      correlation of nongravitational signals with low-redshift gravitational probes.
      This method allows us to enhance the signal to noise from the regions of the
      Universe where the DM-induced emission is preferentially generated. We
      demonstrate the power of this approach by focusing on GeV-TeV DM and on the
      recent cross-correlation analysis between the 2MASS galaxy catalogue and the
      Fermi-LAT gamma-ray maps. We show that this technique is more sensitive than
      other extragalactic gamma-ray probes, such as the energy spectrum and angular
      autocorrelation of the extragalactic background, and emission from clusters of
      galaxies. Intriguingly, we find that the measured cross-correlation can be well
      fitted by a DM component, with a thermal annihilation cross section and mass
      between 10 and 100 GeV, depending on the small-scale DM properties and gamma-ray
      production mechanism. This solicits further data collection and dedicated
      analyses. 

PMID- 26196971
TI  - Color Confinement and Screening in the theta Vacuum of QCD.
AB  - QCD perturbation theory ignores the compact nature of the SU(3) gauge group that
      gives rise to the periodic theta vacuum of the theory. We propose to modify the
      gluon propagator to reconcile perturbation theory with the anomalous Ward
      identities for the topological current in the theta vacuum. As a result, the
      gluon couples to the Veneziano ghost describing the tunneling transitions between
      different Chern-Simons sectors of the vacuum; we call the emerging gluon dressed
      by ghost loops a "glost." We evaluate the glost propagator and find that it has
      the form G(p)=(p(2)+chi(top)/p(2))(-1) where chi(top) is the Yang-Mills
      topological susceptibility related to the eta' mass by the Witten-Veneziano
      relation; this propagator describes the confinement of gluons at distances
      ~chi(top)(-1/4)?1  fm. The same functional form of the propagator was originally
      proposed by Gribov as a solution to the gauge copies problem that plagues
      perturbation theory. The resulting running coupling coincides with the
      perturbative one at p(2)??[chi(top)], but in the infrared region either freezes
      (in pure Yang-Mills theory) or vanishes (in full QCD with light quarks), in
      accord with experimental evidence. Our scenario makes explicit the connection
      between confinement and topology of the QCD vacuum; we discuss the implications
      for spin physics, high energy scattering, and the physics of quark-gluon plasma.

PMID- 26196972
TI  - High-Accuracy CO(2) Line Intensities Determined from Theory and Experiment.
AB  - Atmospheric CO(2) concentrations are being closely monitored by remote sensing
      experiments which rely on knowing line intensities with an uncertainty of 0.5% or
      better. Most available laboratory measurements have uncertainties much larger
      than this. We report a joint experimental and theoretical study providing
      rotation-vibration line intensities with the required accuracy. The ab initio
      calculations are extendible to all atmospherically important bands of CO(2) and
      to its isotologues. As such, they will form the basis for detailed CO(2)
      spectroscopic line lists for future studies.

PMID- 26196973
TI  - Quantum Magnetism and Topological Ordering via Rydberg Dressing near Forster
      Resonances.
AB  - We devise a cold-atom approach to realizing a broad range of bilinear quantum
      magnets. Our scheme is based on off-resonant single-photon excitation of Rydberg
      P states (Rydberg dressing), whose strong interactions are shown to yield
      controllable XYZ interactions between effective spins, represented by different
      atomic ground states. The distinctive features of Forster-resonant Rydberg atom
      interactions are exploited to enhance the effectiveness of Rydberg dressing and,
      thereby, yield large spin interactions that greatly exceed the corresponding
      decoherence rates. We illustrate the concept on a spin-1 chain implemented with
      cold rubidium atoms, and demonstrate that this permits the dynamical preparation
      of topological magnetic phases. Generally, the described approach provides a
      viable route to exploring quantum magnetism with dynamically tunable
      (an)isotropic interactions as well as variable space and spin dimensions in cold
      atom experiments. 

PMID- 26196974
TI  - Rydberg Electrons in a Bose-Einstein Condensate.
AB  - We investigate a hybrid system composed of ultracold Rydberg atoms immersed in an
      atomic Bose-Einstein condensate (BEC). The coupling between Rydberg electrons and
      BEC atoms leads to excitations of phonons, the exchange of which induces a Yukawa
      interaction between Rydberg atoms. Because of the small electron mass, the
      effective charge associated with this quasiparticle-mediated interaction can be
      large. Its range, equal to the BEC healing length, is tunable using Feshbach
      resonances to adjust the scattering length between BEC atoms. We find that for
      small healing lengths, the distortion of the BEC can "image" the Rydberg electron
      wave function, while for large healing lengths the induced attractive Yukawa
      potentials between Rydberg atoms are strong enough to bind them. 

PMID- 26196975
TI  - Quantum Electrodynamical Corrections to Energy Levels of Diatomic Quasimolecules.
AB  - We elaborate an ab initio approach for the evaluation of the one-loop quantum
      electrodynamical corrections to energy levels of diatomic quasimolecules. The
      approach accounts for the interaction between an electron and two nuclei in all
      orders in Zalpha and can be applied for a wide range of internuclear distances,
      up to R~1000  fm. Based on the developed theory, detailed calculations are
      performed for the self-energy and vacuum-polarization corrections to the energy
      of the 1sigma(g) ground state of the U(92+)-U(91+) dimer that can be produced in
      slow ion-ion collisions. The calculations predict the remarkable energy shift
      that arises due to the nonspherical contributions to the electron-nuclei
      potential taken beyond the standard monopole approximation.

PMID- 26196976
TI  - Multiboson Correlation Interferometry with Arbitrary Single-Photon Pure States.
AB  - We provide a compact full description of multiboson correlation measurements of
      arbitrary order N in passive linear interferometers with arbitrary input single
      photon pure states. This allows us to physically analyze the novel problem of
      multiboson correlation sampling at the output of random linear interferometers.
      Our results also describe general multiboson correlation landscapes for an
      arbitrary number of input single photons and arbitrary interferometers. In
      particular, we use two different schemes to demonstrate, respectively, arbitrary
      order quantum beat interference and 100% visibility entanglement correlations
      even for input photons distinguishable in their frequencies. 

PMID- 26196977
TI  - Three-Dimensional Dynamic Localization of Light from a Time-Dependent Effective
      Gauge Field for Photons.
AB  - We introduce a method to achieve the three-dimensional dynamic localization of
      light. We consider a dynamically modulated resonator lattice that has been
      previously shown to exhibit an effective gauge potential for photons. When such
      an effective gauge potential varies sinusoidally in time, dynamic localization of
      light can be achieved. Moreover, while previous works on such an effective gauge
      potential for photons were carried out in the regime where the rotating wave
      approximation is valid, the effect of dynamic localization persists even when the
      counterrotating term is taken into count. 

PMID- 26196978
TI  - Rayleigh-Brillouin Scattering in Binary-Gas Mixtures.
AB  - Precise measurements are performed on spectral line shapes of spontaneous
      Rayleigh-Brillouin scattering in mixtures of the noble gases Ar and Kr, with He.
      Admixture of a light He atomic fraction results in marked changes of the spectra,
      although in all experiments He is merely a spectator atom: it affects the
      relaxation of density fluctuations of the heavy constituent, but its contribution
      to the scattered light intensity is negligibly small. The results are compared to
      a theory for the spectral line shape without adjustable parameters, yielding
      excellent agreement for the case of binary monatomic gases, signifying a step
      towards modeling and understanding of light scattering in more complex molecular
      media. 

PMID- 26196979
TI  - Simple Method to Generate Terawatt-Attosecond X-Ray Free-Electron-Laser Pulses.
AB  - X-ray free-electron lasers (XFELs) are cutting-edge research tools that produce
      almost fully coherent radiation with high power and short-pulse length with
      applications in multiple science fields. There is a strong demand to achieve even
      shorter pulses and higher radiation powers than the ones obtained at state-of-the
      art XFEL facilities. In this context we propose a novel method to generate
      terawatt-attosecond XFEL pulses, where an XFEL pulse is pushed through several
      short good-beam regions of the electron bunch. In addition to the elements of
      conventional XFEL facilities, the method uses only a multiple-slotted foil and
      small electron delays between undulator sections. Our scheme is thus simple,
      compact, and easy to implement both in already operating as well as future XFEL
      projects. We present numerical simulations that confirm the feasibility and
      validity of our proposal. 

PMID- 26196980
TI  - X-Point-Position-Dependent Intrinsic Toroidal Rotation in the Edge of the TCV
      Tokamak.
AB  - Edge intrinsic rotation was investigated in Ohmic L-mode discharges on the
      Tokamak a Configuration Variable, scanning the major radial position of the X
      point, R(X). Edge rotation decreased linearly with increasing R(X), vanishing or
      becoming countercurrent for an outboard X point, in agreement with theoretical
      expectations. The core rotation profile shifted fairly rigidly with the edge
      rotation, changing the central rotation speed by more than a factor of two. Core
      rotation reversals had little effect on the edge rotation velocity. Edge rotation
      was modestly more countercurrent in unfavorable than favorable ?B shots.

PMID- 26196981
TI  - Excitation of Chirping Whistler Waves in a Laboratory Plasma.
AB  - Whistler mode chorus emissions with a characteristic frequency chirp are
      important magnetospheric waves, responsible for the acceleration of outer
      radiation belt electrons to relativistic energies and also for the scattering
      loss of these electrons into the atmosphere. Here, we report on the first
      laboratory experiment where whistler waves exhibiting fast frequency chirping
      have been artificially produced using a beam of energetic electrons launched into
      a cold plasma. Frequency chirps are only observed for a narrow range of plasma
      and beam parameters, and show a strong dependence on beam density, plasma
      density, and magnetic field gradient. Broadband whistler waves similar to
      magnetospheric hiss are also observed, and the parameter ranges for each emission
      are quantified. 

PMID- 26196982
TI  - Self-Similar Theory of Thermal Conduction and Application to the Solar Wind.
AB  - We propose a self-similar kinetic theory of thermal conductivity in a magnetized
      plasma, and discuss its application to the solar wind. We study a collisional
      kinetic equation in a spatially expanding magnetic flux tube, assuming that the
      magnetic field strength, the plasma density, and the plasma temperature decline
      as power laws of distance along the tube. We demonstrate that the electron
      kinetic equation has a family of scale-invariant solutions for a particular
      relation among the magnetic-, density-, and temperature-scaling exponents. These
      solutions describe the heat flux as a function of the temperature Knudsen number
      gamma, which we require to be constant along the flux tube. We observe that self
      similarity may be realized in the solar wind; for the Helios data 0.3-1  AU we
      find that the scaling exponents for density, temperature, and heat flux are close
      to those dictated by scale invariance. We find steady-state solutions of the self
      similar kinetic equation numerically, and show that these solutions accurately
      reproduce the electron strahl population seen in the solar wind, as well as the
      measured heat flux. 

PMID- 26196983
TI  - Instability of the Superfluid Flow as Black-Hole Lasing Effect.
AB  - We show that the critical velocity of a superfluid flow through a penetrable
      barrier coincides with the onset of the analog black-hole lasing effect. This
      dynamical instability is triggered by modes resonating in an effective cavity
      formed by two horizons enclosing the barrier. The location of the horizons is set
      by v(x)=c(x), with v(x),c(x) being the local fluid velocity and sound speed,
      respectively. We compute the critical velocity analytically and show that it is
      univocally determined by the configuration of the horizons. In the limit of broad
      barriers, the continuous spectrum at the origin of the Hawking-like radiation and
      of the Landau energetic instability is recovered. 

PMID- 26196984
TI  - Mesoscopic Impurities Expose a Nucleation-Limited Regime of Crystal Growth.
AB  - Nanoscale self-assembly is naturally subject to impediments at the nanoscale. The
      recently developed ability to follow processes at the molecular level forces us
      to resolve older, coarse-grained concepts in terms of their molecular mechanisms.
      In this Letter, we highlight one such example. We present evidence based on
      experimental and simulation data that one of the cornerstones of crystal growth
      theory, the Cabrera-Vermilyea model of step advancement in the presence of
      impurities, is based on incomplete physics. We demonstrate that the piercing of
      an impurity fence by elementary steps is not solely determined by the Gibbs
      Thomson effect, as assumed by Cabrera-Vermilyea. Our data show that for
      conditions leading up to growth cessation, step retardation is dominated by the
      formation of critically sized fluctuations. The growth recovery of steps is
      counter to what is typically assumed, not instantaneous. Our observations on
      mesoscopic impurities for lysozyme expose a nucleation-dominated regime of growth
      that has not been hitherto considered, where the system alternates between zero
      and near-pure velocity. The time spent by the system in arrest is the nucleation
      induction time required for the step to amass a supercritical fluctuation that
      pierces the impurity fence. 

PMID- 26196985
TI  - Strong Asymmetric Charge Carrier Dependence in Inelastic Electron Tunneling
      Spectroscopy of Graphene Phonons.
AB  - The observation of phonons in graphene by inelastic electron tunneling
      spectroscopy has been met with limited success in previous measurements arising
      from weak signals and other spectral features which inhibit a clear distinction
      between phonons and miscellaneous excitations. Utilizing a back-gated graphene
      device that allows adjusting the global charge carrier density, we introduce an
      averaging method where individual tunneling spectra at varying charge carrier
      density are combined into one representative spectrum. This method improves the
      signal for inelastic transitions while it suppresses dispersive spectral
      features. We thereby map the total graphene phonon density of states, in good
      agreement with density functional calculations. Unexpectedly, an abrupt change in
      the phonon intensity is observed when the graphene charge carrier type is
      switched through a variation of the back-gate electrode potential. This sudden
      variation in phonon intensity is asymmetric in the carrier type, depending on the
      sign of the tunneling bias. 

PMID- 26196986
TI  - Observation of Localized States in Lieb Photonic Lattices.
AB  - We present the first experimental demonstration of a new type of localized state
      in the continuum, namely, compacton-like linear states in flat-band lattices. To
      this end, we employ photonic Lieb lattices, which exhibit three tight-binding
      bands, with one being perfectly flat. Discrete predictions are confirmed by
      realistic continuous numerical simulations as well as by direct experiments. Our
      results could be of great importance for fundamental physics as well as for
      various applications where light needs to be conducted in a diffractionless and
      localized manner over long distances. 

PMID- 26196987
TI  - Observation of a Localized Flat-Band State in a Photonic Lieb Lattice.
AB  - We demonstrate the first experimental realization of a dispersionless state, in a
      photonic Lieb lattice formed by an array of optical waveguides. This engineered
      lattice supports three energy bands, including a perfectly flat middle band with
      an infinite effective mass. We analyze, both experimentally and theoretically,
      the evolution of well-prepared flat-band states, and show their remarkable
      robustness, even in the presence of disorder. The realization of flat-band states
      in photonic lattices opens an exciting door towards quantum simulation of flat
      band models in a highly controllable environment. 

PMID- 26196988
TI  - Low Barrier Carbon Induced CO Dissociation on Stepped Cu.
AB  - Using x-ray photoelectron spectroscopy we observe the breaking of the strong
      interatomic bond in molecular CO at low temperature on a stepped Cu surface.
      Since the electronic structure of Cu does not allow for the splitting of CO at
      such low temperatures it suggests that there may be a less obvious pathway for
      the process. Through x-ray photoelectron spectroscopy we can clearly identify
      products associated with the dissociation of CO and the subsequent formation of
      stable graphitic carbon on the surface. However, the dissociation of CO can be
      inhibited when the stepped Cu surface is kept clean from surface carbon. These
      observations imply that the reaction is driven by the presence of small amounts
      of weakly bound carbon at the surface. Density-functional theory calculations
      confirm that carbon atoms on a stepped Cu surface indeed are the preferred
      adsorption sites for CO, which increases the stabilization of CO on the surface
      and weakens the C-O bond. This results in the breaking of the C-O bond at the
      step edge via the Boudouard reaction (2CO(ads)->C(ads)+CO(2)) with a barrier of
      0.71 eV.

PMID- 26196989
TI  - Accurate Extraction of Electrostatic Force by a Voltage-Pulse Force Spectroscopy.
AB  - The classification of interaction forces between two approaching bodies is
      important in a wide range of research fields. Here, we propose a method to
      unambiguously extract the electrostatic force (F(ele)), which is one of the most
      significant forces. This method is based on the measurement of the energy
      dissipation under applied voltage pulse between an atomic force microscopy (AFM)
      tip and sample. It allowed us to obtain F(ele) as a function of the tip-sample
      distance and voltage including the distance-independent part, to which
      conventional AFM is insensitive. The obtained F(ele) curves nicely fit the
      analytical model, enabling estimation of the geometry of the tip. The distance
      dependent contact potential difference could also be correctly obtained by the
      measured F(ele), opening an alternative route to quantitative Kelvin probe force
      microscopy.

PMID- 26196990
TI  - UO(2) Oxidative Corrosion by Nonclassical Diffusion.
AB  - Using x-ray scattering, spectroscopy, and density-functional theory, we determine
      the structure of the oxidation front when a UO(2) (111) surface is exposed to
      oxygen at ambient conditions. In contrast to classical diffusion and previously
      reported bulk UO(2+x) structures, we find oxygen interstitials order into a
      nanoscale superlattice with three-layer periodicity and uranium in three
      oxidation states: IV, V, and VI. This oscillatory diffusion profile is driven by
      the nature of the electron transfer process, and has implications for
      understanding the initial stages of oxidative corrosion in materials at the
      atomistic level.

PMID- 26196991
TI  - Electronics with Correlated Oxides: SrVO(3)/SrTiO(3) as a Mott Transistor.
AB  - We employ density functional theory plus dynamical mean field theory and identify
      the physical origin of why two layers of SrVO(3) on a SrTiO(3) substrate are
      insulating: the thin film geometry lifts the orbital degeneracy, which in turn
      triggers a first-order Mott-Hubbard transition. Two layers of SrVO(3) are just at
      the verge of a Mott-Hubbard transition and hence ideally suited for technological
      applications of the Mott-Hubbard transition: the heterostructure is highly
      sensitive to strain, electric field, and temperature. A gate voltage can also
      switch between metal (ON) and insulator (OFF), so that a transistor with ideal ON
      OFF switching properties is realized.

PMID- 26196992
TI  - Bad-Metal Behavior Reveals Mott Quantum Criticality in Doped Hubbard Models.
AB  - Bad-metal (BM) behavior featuring linear temperature dependence of the
      resistivity extending to well above the Mott-Ioffe-Regel (MIR) limit is often
      viewed as one of the key unresolved signatures of strong correlation. Here we
      associate the BM behavior with the Mott quantum criticality by examining a fully
      frustrated Hubbard model where all long-range magnetic orders are suppressed, and
      the Mott problem can be rigorously solved through dynamical mean-field theory. We
      show that for the doped Mott insulator regime, the coexistence dome and the
      associated first-order Mott metal-insulator transition are confined to extremely
      low temperatures, while clear signatures of Mott quantum criticality emerge
      across much of the phase diagram. Remarkable scaling behavior is identified for
      the entire family of resistivity curves, with a quantum critical region covering
      the entire BM regime, providing not only insight, but also quantitative
      understanding around the MIR limit, in agreement with the available experiments. 

PMID- 26196993
TI  - Helicity-Driven Ratchet Effect Enhanced by Plasmons.
AB  - We demonstrate that the ratchet effect-a radiation-induced direct current in
      periodically modulated structures with built-in asymmetry-is dramatically
      enhanced in the vicinity of the plasmonic resonances and has a nontrivial
      polarization dependence. For a circular polarization, the current component,
      perpendicular to the modulation direction, changes sign with the inversion of the
      radiation helicity. In the high-mobility structures, this component might
      increase by several orders of magnitude due to the plasmonic effects and exceed
      the current component in the modulation direction. Our theory also predicts that
      in the dirty systems, where the plasma resonances are suppressed, the ratchet
      current is controlled by the Maxwell relaxation. 

PMID- 26196994
TI  - Magnetism and Interaction-Induced Gap Opening in Graphene with Vacancies or
      Hydrogen Adatoms: Quantum Monte Carlo Study.
AB  - We study the electronic properties of graphene with a finite concentration of
      vacancies or other resonant scatterers by a straightforward lattice quantum Monte
      Carlo calculation. Taking into account a realistic long-range Coulomb
      interaction, we calculate the distribution of the spin density associated with
      midgap states and demonstrate antiferromagnetic ordering. An energy gap is open
      due to interaction effects, both in the bare graphene spectrum and in the vacancy
      or impurity bands. In the case of a 5% concentration of resonant scatterers the
      latter gap is estimated to be 0.7 eV and 1.1 eV for graphene on boron nitride and
      freely suspended graphene, respectively. 

PMID- 26196995
TI  - Magnetization Signatures of Light-Induced Quantum Hall Edge States.
AB  - Circularly polarized light opens a gap in the Dirac spectrum of graphene and
      topological insulator (TI) surfaces, thereby inducing a quantum Hall-like phase.
      We propose to detect the accompanying edge states and their current by the
      magnetic field they produce. The topological nature of the edge states is
      reflected in the mean orbital magnetization of the sample, which shows a
      universal linear dependence as a function of a generalized chemical potential
      independent of the driving details and the properties of the material. The
      proposed protocol overcomes several typically encountered problems in the
      realization and measurement of Floquet phases, including the destructive effects
      of phonons and coupled electron baths and provides a way to occupy the induced
      edge states selectively. We estimate practical experimental parameters and
      conclude that the magnetization signature of the Floquet topological phase may be
      detectable with current techniques. 

PMID- 26196996
TI  - Inequivalence of Single-Particle and Population Lifetimes in a Cuprate
      Superconductor.
AB  - We study optimally doped Bi-2212 (T(c)=96  K) using femtosecond time- and angle
      resolved photoelectron spectroscopy. Energy-resolved population lifetimes are
      extracted and compared with single-particle lifetimes measured by equilibrium
      photoemission. The population lifetimes deviate from the single-particle
      lifetimes in the low excitation limit by 1-2 orders of magnitude. Fundamental
      considerations of electron scattering unveil that these two lifetimes are in
      general distinct, yet for systems with only electron-phonon scattering they
      should converge in the low-temperature, low-fluence limit. The qualitative
      disparity in our data, even in this limit, suggests that scattering channels
      beyond electron-phonon interactions play a significant role in the electron
      dynamics of cuprate superconductors.

PMID- 26196997
TI  - Zigzag and Checkerboard Magnetic Patterns in Orbitally Directional Double
      Exchange Systems.
AB  - We analyze a t(2g) double-exchange system where the orbital directionality of the
      itinerant degrees of freedom is a key dynamical feature that self-adjusts in
      response to doping and leads to a phase diagram dominated by two classes of
      ground states with zigzag and checkerboard patterns. The prevalence of distinct
      orderings is tied to the formation of orbital molecules that in one-dimensional
      paths make insulating zigzag states kinetically more favorable than metallic
      stripes, thus allowing for a novel doping-induced metal-to-insulator transition.
      We find that the basic mechanism that controls the magnetic competition is the
      breaking of orbital directionality through structural distortions, and highlight
      the consequences of the interorbital Coulomb interaction.

PMID- 26196792
TI  - Search for a Charged Higgs Boson Produced in the Vector-Boson Fusion Mode with
      Decay H(+/-)->W(+/-)Z using pp Collisions at ?s=8  TeV with the ATLAS Experiment.
AB  - A search for a charged Higgs boson, H(+/-), decaying to a W(+/-) boson and a Z
      boson is presented. The search is based on 20.3  fb(-1) of proton-proton
      collision data at a center-of-mass energy of 8 TeV recorded with the ATLAS
      detector at the LHC. The H(+/-) boson is assumed to be produced via vector-boson
      fusion and the decays W(+/-)->qq' and Z->e(+)e(-)/MU(+)MU(-) are considered. The
      search is performed in a range of charged Higgs boson masses from 200 to 1000
      GeV. No evidence for the production of an H(+/-) boson is observed. Upper limits
      of 31-1020 fb at 95% C.L. are placed on the cross section for vector-boson fusion
      production of an H(+/-) boson times its branching fraction to W(+/-)Z. The limits
      are compared with predictions from the Georgi-Machacek Higgs triplet model.

PMID- 26196998
TI  - Direct Observation of Entropy-Driven Electron-Hole Pair Separation at an Organic
      Semiconductor Interface.
AB  - How an electron-hole pair escapes the Coulomb potential at a donor-acceptor
      interface has been a key issue in organic photovoltaic research. Recent evidence
      suggests that long-distance charge separation can occur on ultrafast time scales,
      yet the underlying mechanism remains unclear. Here we use charge transfer
      excitons (CTEs) across an organic semiconductor-vacuum interface as a model and
      show that nascent hot CTEs can spontaneously climb up the Coulomb potential
      within 100 fs. This process is driven by entropic gain due to the rapid rise in
      density of states with increasing electron-hole separation. In contrast, the
      lowest CTE cannot delocalize, but undergoes self-trapping and recombination. 

PMID- 26197004
TI  - Affleck-Kennedy-Lieb-Tasaki State on a Honeycomb Lattice from t(2g) Orbitals.
AB  - The two-dimensional Affleck-Kennedy-Lieb-Tasaki (AKLT) model on a honeycomb
      lattice has been shown to be a universal resource for quantum computation. In
      this valence bond solid, however, the spin interactions involve higher powers of
      the Heisenberg coupling (S[over ->](I).S[over ->](j))(n), making these states
      seemingly unrealistic on bipartite lattices, where one expects a simple
      antiferromagnetic order. We show that those interactions can be generated by
      orbital physics in multiorbital Mott insulators. We focus on t(2g) electrons on
      the honeycomb lattice and propose a physical realization of the spin-3/2 AKLT
      state. We find a phase transition from the AKLT to the Neel state on increasing
      Hund's rule coupling, which is confirmed by density matrix renormalization group
      simulations. An experimental signature of the AKLT state consists of protected,
      free S=1/2 spins on lattice vacancies, which may be detected in the spin
      susceptibility.

PMID- 26197005
TI  - Spin-Lattice Order in One-Dimensional Conductors: Beyond the RKKY Effect.
AB  - We investigate magnetic order in a lattice of classical spins coupled to an
      isotropic gas of one-dimensional conduction electrons via local exchange
      interactions. The frequently discussed Ruderman-Kittel-Kasuya-Yosida effective
      exchange model for this system predicts that spiral order is always preferred.
      Here we consider the problem nonperturbatively, and find that such order vanishes
      above a critical value of the exchange coupling that depends strongly on the
      lattice spacing. The critical coupling tends to zero as the lattice spacing
      becomes commensurate with the Fermi wave vector, signaling the breakdown of the
      perturbative Ruderman-Kittel-Kasuya-Yosida picture, and spiral order, even at
      weak coupling. We provide the exact phase diagram for arbitrary exchange coupling
      and lattice spacing, and discuss its stability. Our results shed new light on the
      problem of utilizing a spiral spin-lattice state to drive a one-dimensional
      superconductor into a topological phase. 

PMID- 26197007
TI  - Topological Spin Glass in Diluted Spin Ice.
AB  - It is a salient experimental fact that a large fraction of candidate spin liquid
      materials freeze as the temperature is lowered. The question naturally arises
      whether such freezing is intrinsic to the spin liquid ("disorder-free
      glassiness") or extrinsic, in the sense that a topological phase simply coexists
      with standard freezing of impurities. Here, we demonstrate a surprising third
      alternative, namely, that freezing and topological liquidity are inseparably
      linked. The topological phase reacts to the introduction of disorder by
      generating degrees of freedom of a new type (along with interactions between
      them), which in turn undergo a freezing transition while the topological phase
      supporting them remains intact. 

PMID- 26197006
TI  - Narrow Magnonic Waveguides Based on Domain Walls.
AB  - The channeling of spin waves with domain walls in ultrathin ferromagnetic films
      is demonstrated theoretically and through micromagnetics simulations. It is shown
      that propagating excitations localized to the wall, which appear in the frequency
      gap of bulk spin wave modes, can be guided in curved geometries and propagate in
      close proximity to other channels. For Neel-type walls arising from a
      Dzyaloshinskii-Moriya interaction, the channeling is strongly nonreciprocal and
      group velocities can exceed 1  km/s in the long wavelength limit for certain
      propagation directions. The channeled modes represent an unusual analogy of
      whispering gallery waves that are one dimensional and nonreciprocal with this
      interaction. Moreover, a sufficiently strong Dzyaloshinskii-Moriya interaction
      can create a degeneracy of channeled and propagating modes at a critical wave
      vector. 

PMID- 26197000
TI  - Single to Multiquasiparticle Excitations in the Itinerant Helical Magnet
      CeRhIn(5).
AB  - CeRhIn(5) is an itinerant magnet where the Ce(3+) spins order in a simple helical
      phase. We investigate the spin excitations and observe sharp spin waves
      parameterized by a nearest-neighbor exchange, J(RKKY)=0.88+/-0.05  meV. At higher
      energies, the spin fluctuations are heavily damped, where single-quasiparticle
      excitations are replaced by a momentum- and energy-broadened continuum
      constrained by kinematics of energy and momentum conservation. The delicate
      energy balance between localized and itinerant characters results in the
      breakdown of the single-quasiparticle picture in CeRhIn(5).

PMID- 26197001
TI  - Superconductivity in the Graphite Intercalation Compound BaC(6).
AB  - Among many two-dimensional (2D) high T(C) superconductors, graphite intercalation
      compounds (GICs) are the most famous intercalation family, which are classified
      as typical electron-phonon mediated superconductors. We show unambiguous
      experimental facts that BaC(6), the superconductivity of which has been missing
      for many years so far among various alkaline earth metal (Ca, Sr, and Ba)
      intercalted GICs, exhibits superconductivity at T(C)=65  mK. By adding this
      finding as the additional experimental point, a complete figure displaying the
      relationship between T(C) and interlayer distance (d) for GICs is now provided,
      and their possible superconducting mechanisms raised so far are revisited. The
      present study settles a long-running debate between theories and experiments on
      the superconductivity in the first stage GICs.

PMID- 26197003
TI  - Tuning the Magnetic Anisotropy at a Molecule-Metal Interface.
AB  - We demonstrate that a C(60) overlayer enhances the perpendicular magnetic
      anisotropy of a Co thin film, inducing an inverse spin reorientation transition
      from in plane to out of plane. The driving force is the (60)/Co interfacial
      magnetic anisotropy that we have measured quantitatively in situ as a function of
      the (60) coverage. Comparison with state-of-the-art ab initio calculations show
      that this interfacial anisotropy mainly arises from the local hybridization
      between (60) p(z) and Co d(z(2)) orbitals. By generalizing these arguments, we
      also demonstrate that the hybridization of (60) with a Fe(110) surface decreases
      the perpendicular magnetic anisotropy. These results open the way to tailor the
      interfacial magnetic anisotropy in organic-material-ferromagnet systems.

PMID- 26196999
TI  - Mutual Independence of Critical Temperature and Superfluid Density under Pressure
      in Optimally Electron-Doped Superconducting LaFeAsO(1-x)F(x).
AB  - The superconducting properties of LaFeAsO(1-x)F(x) under conditions of optimal
      electron doping are investigated upon the application of external pressure up to
      ~23  kbar. Measurements of muon-spin spectroscopy and dc magnetometry evidence a
      clear mutual independence between the critical temperature T(c) and the low
      temperature saturation value for the ratio n(s)/m(*) (superfluid density over
      effective band mass of Cooper pairs). Remarkably, a dramatic increase of ~30% is
      reported for n(s)/m(*) at the maximum pressure value while T(c) is substantially
      unaffected in the whole accessed experimental window. We argue and demonstrate
      that the explanation for the observed results must take the effect of nonmagnetic
      impurities on multiband superconductivity into account. In particular, the unique
      possibility to modify the ratio between intraband and interband scattering rates
      by acting on structural parameters while keeping the amount of chemical disorder
      constant is a striking result of our proposed model.

PMID- 26197002
TI  - Anisotropy-Tuned Magnetic Order in Pyrochlore Iridates.
AB  - The magnetic behavior of polycrystalline samples of Er(2)Ir(2)O(7) and
      Tb(2)Ir(2)O(7) pyrochlores is studied by magnetization measurements and neutron
      diffraction. Both compounds undergo a magnetic transition at 140 and 130 K,
      respectively, associated with an ordering of the Ir sublattice, signaled by
      thermomagnetic hysteresis. In Tb(2)Ir(2)O(7), we show that the Ir molecular field
      leads the Tb magnetic moments to order below 40 K in the all-in-all-out magnetic
      arrangement. No sign of magnetic long-range order on the Er sublattice is
      evidenced in Er(2)Ir(2)O(7) down to 0.6 K where a spin freezing is detected.
      These contrasting behaviors result from the competition between the Ir molecular
      field and the different single-ion anisotropy of the rare-earth elements on which
      it is acting. Additionally, this strongly supports the all-in-all-out iridium
      magnetic order.

PMID- 26197008
TI  - Dynamics and Correlations among Soft Excitations in Marginally Stable Glasses.
AB  - Marginal stability is the notion that stability is achieved, but only barely so.
      This property constrains the ensemble of configurations explored at low
      temperature in a variety of systems, including spin, electron, and structural
      glasses. A key feature of marginal states is a (saturated) pseudogap in the
      distribution of soft excitations. We examine how such pseudogaps appear
      dynamically by studying the Sherrington-Kirkpatrick (SK) spin glass. After
      revisiting and correcting the multi-spin-flip criterion for local stability, we
      show that stationarity along the hysteresis loop requires soft spins to be
      frustrated among each other, with a correlation diverging as C(lambda)~1/lambda,
      where lambda is the stability of the more stable spin. We explain how this arises
      spontaneously in a marginal system and develop an analogy between the spin
      dynamics in the SK model and random walks in two dimensions. We discuss analogous
      frustrations among soft excitations in short range glasses and how to detect them
      experimentally. We also show how these findings apply to hard sphere packings. 

PMID- 26197009
TI  - Engineering a Spin-Orbital Magnetic Insulator by Tailoring Superlattices.
AB  - In 5d Ir oxides with an interplay of spin-orbit coupling and electron
      correlations, we have tailored a spin-orbital magnetic insulator out of a
      semimetal SrIrO(3) by tuning the structure through superlattices [(SrIrO(3))(m),
      SrTiO(3)] (m=1,2,3,4, and infinity). We observed the systematic decrease of the
      magnetic ordering temperature and the resistivity as a function of m. The
      transition from the semimetal to the insulator is found to be closely linked to
      the appearance of magnetism at m?3. Long range magnetic ordering was realized
      even in the m=1 single layer superlattice, implying that the design and
      realization of novel electronic phases is feasible at the level of a single
      atomic layer in complex Ir oxides.

PMID- 26197010
TI  - Antiferromagnetic Dichroism in a Complex Multisublattice Magnetoelectric
      CuB(2)O(4).
AB  - Magnetic control of the crystal chirality was announced by Saito et al. [Phys.
      Rev. Lett. 101, 117402 (2008)] on the ground of experiments in CuB(2)O(4). This
      claim has raised a sharp dispute in the literature because it seemed to
      contradict the fundamental symmetry principles. We settle this dispute on the
      basis of a high-resolution optical spectroscopy study of excitonic transitions in
      CuB(2)O(4). We find that a large sublattice-sensitive antiferromagnetic linear
      dichroism (LD) emerges at the Neel temperature T(N)=21  K and show how it could
      simulate a "magnetic-field control of the crystal chirality." We prove that the
      discovered LD is related microscopically to the magnetic Davydov splitting. This
      LD is highly sensitive to subtle changes in the spin subsystems, which allowed us
      to observe a splitting of the phase transition into an incommensurate magnetic
      phase into two transitions (T(1)(*)=8.5 and T(2)(*)=7.9  K) and to suggest
      elliptical spiral structures below T(1)(*), instead of a simple circular helix
      proposed earlier.

PMID- 26197011
TI  - Unraveling the Mesoscopic Character of Quantum Dots in Nanophotonics.
AB  - We provide a microscopic theory for semiconductor quantum dots that explains the
      pronounced deviations from the prevalent point-dipole description that were
      recently observed in spectroscopic experiments on quantum dots in photonic
      nanostructures. The deviations originate from structural inhomogeneities
      generating a large circular quantum current density that flows inside the quantum
      dot over mesoscopic length scales. The model is supported by the experimental
      data, where a strong variation of the multipolar moments across the emission
      spectrum of quantum dots is observed. Our work enriches the physical
      understanding of quantum dots and is of significance for the fields of
      nanophotonics, quantum photonics, and quantum-information science, where quantum
      dots are actively employed. 

PMID- 26197012
TI  - Bistable Magnetism and Potential for Voltage-Induced Spin Crossover in Dilute
      Magnetic Ferroelectrics.
AB  - A first-principles investigation into the magnetic ferroelectric PbTi(1
      x)Co(x)O(3) has revealed a bi-stable magnetic system with strong spin-lattice
      coupling. The local distortions induced by the low-spin to high-spin crossover
      are ferroelectric in nature, and are characterized by the displacement of the
      dopant ion with respect to the surrounding O(6) octahedral cage. We demonstrate
      how this spin-lattice effect could mediate magnetoelectric coupling and possible
      electric field induced spin-crossover, indicating a promising route to voltage
      manipulation of isolated spins in a solid-state system.

PMID- 26197013
TI  - Triangular Spin-Orbit-Coupled Lattice with Strong Coulomb Correlations: Sn Atoms
      on a SiC(0001) Substrate.
AB  - Two-dimensional (2D) atom lattices provide model setups with Coulomb correlations
      that induce competing ground states. Here, SiC emerges as a wide-gap substrate
      with reduced screening. We report the first artificial high-Z atom lattice on
      SiC(0001) by Sn adatoms, based on experimental realization and theoretical
      modeling. Density-functional theory of our triangular structure model closely
      reproduces the scanning tunneling microscopy. Photoemission data show a deeply
      gapped state (~2  eV gap), and, based on our calculations including dynamic mean
      field theory, we argue that this reflects a pronounced Mott-insulating scenario.
      We also find indications that the system is susceptible to antiferromagnetic
      superstructures. Such artificial lattices on SiC(0001) thus offer a novel
      platform for coexisting Coulomb correlations and spin-orbit coupling, with
      bearing for unusual magnetic phases and proposed topological quantum states of
      matter. 

PMID- 26197014
TI  - Optical Polarization of Nuclear Spins in Silicon Carbide.
AB  - We demonstrate optically pumped dynamic nuclear polarization of (29)Si nuclear
      spins that are strongly coupled to paramagnetic color centers in 4H- and 6H-SiC.
      The 99%+/-1% degree of polarization that we observe at room temperature
      corresponds to an effective nuclear temperature of 5  MUK. By combining ab initio
      theory with the experimental identification of the color centers' optically
      excited states, we quantitatively model how the polarization derives from
      hyperfine-mediated level anticrossings. These results lay a foundation for SiC
      based quantum memories, nuclear gyroscopes, and hyperpolarized probes for
      magnetic resonance imaging.

PMID- 26197015
TI  - Giant Acceleration of Diffusion Observed in a Single-Molecule Experiment on F(1)
      ATPase.
AB  - The giant acceleration (GA) of diffusion is a universal phenomenon predicted by
      the theoretical analysis given by Reimann et al. [Phys. Rev. Lett. 87, 010602
      (2001)]. Here we apply the theory of the GA of diffusion to a single-molecule
      experiment on a rotary motor protein, F(1), which is a component of F(o)F(1)
      adenosine triphosphate synthase. We discuss the energetic properties of F(1) and
      identify a high energy barrier of the rotary potential to be 20k(B)T, with the
      condition that the adenosine diphosphates are tightly bound to the F(1) catalytic
      sites. To conclude, the GA of diffusion is useful for measuring energy barriers
      in nonequilibrium and single-molecule experiments.

PMID- 26197016
TI  - Identification of Patient Zero in Static and Temporal Networks: Robustness and
      Limitations.
AB  - Detection of patient zero can give new insights to epidemiologists about the
      nature of first transmissions into a population. In this Letter, we study the
      statistical inference problem of detecting the source of epidemics from a
      snapshot of spreading on an arbitrary network structure. By using exact analytic
      calculations and Monte Carlo estimators, we demonstrate the detectability limits
      for the susceptible-infected-recovered model, which primarily depend on the
      spreading process characteristics. Finally, we demonstrate the applicability of
      the approach in a case of a simulated sexually transmitted infection spreading
      over an empirical temporal network of sexual interactions. 

PMID- 26197017
TI  - Comment on "Abelian Chern-Simons-Maxwell Theory from a Tight-Binding Model of
      Spinless Fermions".

PMID- 26197018
TI  - Observed Variability in Sleeve Gastrectomy Volume and Compliance Does Not
      Correlate to Postoperative Outcomes.
AB  - BACKGROUND: Restrictive bariatric procedures reduce gastric capacity as a primary
      mechanism of action. Intraoperatively, surgeons observe variability in size and
      compliance of specimens. We hypothesized that higher gastric specimen volume or
      tissue compliance would respond better to restrictive procedures. MATERIALS AND
      METHODS: Consecutive patients undergoing laparoscopic sleeve gastrectomy between
      September 2012 and September 2013 were enrolled. Specimens were insufflated at
      graduated pressure points creating pressure volume curves, and compliance was
      calculated. Postoperative weight loss and a hunger scores were recorded.
      Correlations were determined by Spearman correlation. RESULTS: Eighty-four
      patients consented to enrollment. Mean age, weight, and body mass index (BMI)
      were 45 +/- 12 years, 126 +/- 23 kg, and 45.4 +/- 6 m/kg2, respectively. The
      resected specimens varied in insufflated capacity from 0.3 to 1.8 (0.71 +/- 0.32)
      L and compliance varied from 14.3 to 85.7 (36.1 +/- 14.7) cc/mm Hg. Male patients
      had a larger greater curvature length (GCL) (P < 0.001), staple line length (SLL)
      (P = 0.03), gastric volume (GV) (P = 0.002), and gastric compliance (GC) (P <
      0.001). Neither GV nor GC correlated to excess body weight loss (EBWL%) as
      hypothesized. There was an inverse correlation between hunger score and GV (P =
      0.010). The mean 1-month, 3-month, 6-month, and 12-month EBWL was 17.4%, 33.2%,
      43.7%, and 54.1%, respectively. Follow-up was 71.4% at 1 month, 39.3% at 3
      months, 54.8% at 6 months, and 42.9% at 12 months. CONCLUSIONS: Sleeve
      gastrectomy specimens exhibit nearly 6-fold variability in both volume and
      compliance. A large GC is anticipated in male and tall subjects. These
      observations do not appear to be correlated to %EBWL.

PMID- 26197019
TI  - Solutions for low and high accuracy mass spectrometric data matching: a data
      driven annotation strategy in nontargeted metabolomics.
AB  - Ultra high pressure liquid chromatography coupled to mass spectrometry (UHPLC-MS)
      has become a widespread analytical technique in metabolomics investigations,
      however the benefit of high-performance chromatographic separation is often
      blunted due to insufficient mass spectrometric accuracy. A strategy that allows
      for the matching of UHPLC-MS data to highly accurate direct infusion electrospray
      ionization (DI-ESI) Fourier transform ion cyclotron resonance/mass spectrometry
      (FTICR/MS) data is developed in this manuscript. Mass difference network (MDiN)
      based annotation of FTICR/MS data and matching to unique UHPLC-MS peaks enables
      the consecutive annotation of the chromatographic data set. A direct comparison
      of experimental m/z values provided no basis for the matching of both platforms.
      The matching of annotation-based exact neutral masses finally enabled the
      integration of platform specific multivariate statistical evaluations, minimizing
      the danger to compare artifacts generated on either platform. The approach was
      developed on a non-alcoholic fatty liver disease (NAFLD) data set. 

PMID- 26197020
TI  - The half-life of 227Th by direct and indirect measurements.
AB  - Utilising a chemically purified solution the radioactive half-life of (227)Th has
      been determined indirectly by observation of the ingrowth of (223)Ra using an
      ionisation chamber (IC) and for the first time by direct observation of the
      change in activity with time using a high-purity germanium (HPGe) gamma-ray
      spectrometer. The radioactive decay was observed for ~104 days (~5.6 half-lives)
      by gamma-ray spectrometry and approximately 63 days and 72 days (~3.4 and ~3.9
      half-lives) using an ionisation chamber (IC). The resulting half-life values -
      18.695 (4) days (IC) and 18.683 (20) days (HPGe) - are consistent and detailed
      uncertainty budgets are presented for the two measurement techniques. A weighted
      mean of our results of 18.695 (4) days is inconsistent with the most precise
      published half-life value of 18.7176 (52) days (Jordan and Blanke, 1967). A
      critical evaluation of literature data has been performed, indicating a paucity
      of reliable and independent measurements. Selected independent published values
      have been used to determine a recommended half-life of 18.697 (7) days. A method
      has been introduced in the course of this work so that the recommended half-life
      of (227)Th as determined by ingrowth can be modified if a different (223)Ra half
      life has been determined, evaluated and adopted. 

PMID- 26197021
TI  - Does Risk for Malnutrition in Patients Presenting With Fractures Predict Lower
      Quality Measures?
AB  - INTRODUCTION: The purpose of this study was to determine if nutritional screening
      could be used as a predictor for the development of complications and hospital
      readmissions. METHODS: A variation of the Malnutrition Universal Screening Tool
      (MUST) score was collected for all inpatients with orthopaedic trauma on
      admission to our hospital from 2009 to 2011. We retrospectively compared each
      patient's MUST score with the subsequent development of infection, venous
      thromboembolism, respiratory failure, ulceration, or readmission. Finally, a
      chart review was performed to collect comorbidity data and evaluate Charlson
      comorbidity indexes to estimate the overall health of each patient with an
      available MUST. RESULTS: Of the 796 consecutive patients in our total cohort,
      57.7% (n = 459) were of normal nutritional status and 42.3% (n = 337) exhibited
      at least 1 sign of malnutrition. In patients with normal nutrition, 2.8%
      developed at least one of the specified complications, and we observed a
      complication-to-patient ratio of 0.033. In patients with signs of malnutrition,
      8.0% developed at least 1 complication with a complication-to-patient ratio of
      0.101. This difference was significant (P = 0.001). Multivariate regression
      analysis demonstrated that each additional point in a patient's nutrition score
      corresponded to a 49.5% increase in the odds of developing a complication when
      controlling for other factors (odds ratio = 1.495, confidence interval = 1.120
      1.997, P = 0.006). Charlson comorbidity indexes were not significantly associated
      with total complications when MUST scores used were a covariant. DISCUSSION AND
      CONCLUSIONS: Patients treated for fractures and dislocations with any sign of
      malnutrition according to the MUST score were more than twice as likely to
      acquire some combination of infection, venous thromboembolism, respiratory
      failure, or other reason for readmission than those of normal nutritional status.
      Increasing levels of malnourishment corresponded with increasing risk for
      developing complications, whereas these complications were not necessarily
      associated with higher comorbidity. An assessment of a fracture patient's
      nutritional status should be considered a factor in evaluating risks related to
      fracture care. The MUST score is a predictive tool. These data have important
      implications for hospitals whose fiscal reimbursement is dependent on the
      maintenance of defined quality measures. LEVEL OF EVIDENCE: Prognostic Level II.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 26197022
TI  - Vitamin C to Prevent Complex Regional Pain Syndrome in Patients With Distal
      Radius Fractures: A Meta-Analysis of Randomized Controlled Trials.
AB  - OBJECTIVE: To determine whether vitamin C is effective in preventing complex
      regional pain syndrome (CRPS) in patients with distal radius fractures. DATA
      SOURCES: MEDLINE (1946 to present), EMBASE (1974 to present), and The Cochrane
      Library (no date limit) were systematically searched up to September 6, 2014,
      using MeSH and EMTREE headings with free text combinations. STUDY SELECTION:
      Randomized trials comparing vitamin C against placebo were included. No
      exclusions were made during the selection of eligible trials on the basis of
      patient age, sex, fracture severity, or fracture treatment. DATA EXTRACTION: Two
      reviewers independently screened articles, extracted data, and applied the
      Cochrane Risk of Bias tool. Evidence was graded using the Grading of
      Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS:
      Heterogeneity was quantified using the chi test and the I statistic. Outcome data
      were combined with a random effects model. RESULTS: Across 3 trials (n = 890) of
      patients with distal radius fractures, vitamin C did not reduce the risk for CRPS
      (risk ratio = 0.45; 95% confidence interval, 0.18-1.13; I = 70%). This result was
      confirmed in sensitivity analyses to test the importance of missing data because
      of losses to follow-up under varying assumptions. Heterogeneity was explained by
      diagnostic criteria, but not regimen of vitamin C or fracture treatment.
      CONCLUSIONS: The evidence for vitamin C to prevent CRPS in patients with distal
      radius fractures fails to demonstrate a significant benefit. The overall quality
      of the evidence is low, and these results should be interpreted in the context of
      clinical expertise and patient preferences.

PMID- 26197023
TI  - In Response.

PMID- 26197025
TI  - Ethnic differences in fetal size and growth in a multi-ethnic population.
AB  - OBJECTIVES: Impaired or excessive fetal growth is associated with adverse short-
      and long-term health outcomes that differ between ethnic groups. We explored
      ethnic differences in fetal size and growth from mid pregnancy until birth.
      METHODS: Data are from the multi-ethnic STORK-Groruddalen study, a population
      based, prospective cohort of 823 pregnant women and their offspring in Oslo,
      Norway. Measures were z-scores of estimated fetal weight (EFW), head
      circumference (HC), abdominal circumference (AC) and femur length (FL), in
      gestational week 24, 32 and 37, measured by ultrasound, and similar measures at
      birth. Differences in fetal size and growth were assessed using separate Linear
      Mixed Models including all four time points, with ethnic Europeans as reference.
      RESULTS: In week 24 South Asian fetuses had smaller AC, but larger FL than
      Europeans, and slightly lower EFW (-0.17 SD (-0.33, -0.01), p=0.04). Middle
      East/North African fetuses also had larger FL, but similar AC, and hence slightly
      higher EFW (0.18 (0.003, 0.36), p=0.05). Both groups had slower growth of AC, FL
      and EFW from this time until birth, and had -0.61 SD (-0.73, -0.49) and -0.28 SD
      (-0.41, -0.15) lower birth weight respectively. Ethnic East Asians, on the other
      hand, were smaller throughout pregnancy and had -0.58 SD (-0.82, -0.34) lower
      birth weight. Significant ethnic differences remained after adjusting for
      maternal factors. CONCLUSION: We observed ethnic differences in fetal size and
      body proportions already in gestational week 24, and in fetal growth from this
      time until birth, which were only partly explained by key maternal factors.

PMID- 26197024
TI  - Anthony Cerami Award in Translational Medicine: A Journey in Science: The Birth
      of Organ Transplantation with Particular Reference to Alloengraftment Mechanisms.

PMID- 26197026
TI  - Evaluation of the Possible Sources and Controlling Factors of Toxic
      Metals/Metalloids in the Florida Everglades and Their Potential Risk of Exposure.
AB  - The Florida Everglades is an environmentally sensitive wetland ecosystem with a
      number of threatened and endangered fauna species susceptible to the
      deterioration of water quality. Several potential toxic metal sources exist in
      the Everglades, including farming, atmospheric deposition, and human activities
      in urban areas, causing concerns of potential metal exposure risks. However,
      little is known about the pollution status of toxic metals/metalloids of
      potential concern, except for Hg. In this study, eight toxic metals/metalloids
      (Cd, Cr, Pb, Ni, Cu, Zn, As, and Hg) in Everglades soils were investigated in
      both dry and wet seasons. Pb, Cr, As, Cu, Cd, and Ni were identified to be above
      Florida SQGs (sediment quality guidelines) at a number of sampling sites,
      particularly Pb, which had a level of potential risk to organisms similar to that
      of Hg. In addition, a method was developed for quantitative source identification
      and controlling factor elucidation of toxic metals/metalloids by introducing an
      index, enrichment factor (EF), in the conventional multiple regression analysis.
      EFs represent the effects of anthropogenic sources on metals/metalloids in soils.
      Multiple regression analysis showed that Cr and Ni were mainly controlled by
      anthropogenic loading, whereas soil characteristics, in particular natural
      organic matter (NOM), played a more important role for Hg, As, Cd, and Zn. NOM
      may control the distribution of these toxic metals/metalloids by affecting their
      mobility in soils. For Cu and Pb, the effects of EFs and environmental factors
      are comparable, suggesting combined effects of loading and soil characteristics.
      This study is the first comprehensive research with a vast amount of sampling
      sites on the distribution and potential risks of toxic metals/metalloids in the
      Everglades. The finding suggests that in addition to Hg other metals/metalloids
      could also potentially be an environmental problem in this wetland ecosystem.

PMID- 26197027
TI  - Chemotherapy-induced peripheral neurotoxicity.
AB  - PURPOSE OF REVIEW: Chemotherapy-induced peripheral neurotoxicity (CIPN) is
      clinically relevant because it is frequent, it might be dose-limiting, it affects
      the cancer survivors' quality of life, and no treatment is available. Better
      understanding of CIPN might lead to an improvement in its management. RECENT
      FINDINGS: Conventional chemotherapy is a well known cause of peripheral
      neurotoxicity, which mostly manifest with sensory impairment. CIPN has also been
      described for new, highly effective compounds, which are, therefore, limited in
      their more widespread use. Even several 'targeted drugs', which should be free
      from the risk of CIPN by definition, are neurotoxic, occasionally inducing severe
      motor impairment. SUMMARY: Precise definition of CIPN clinical features can be
      obtained by only using validated outcome measures. Therefore, a major aim of
      clinical research is to standardize CIPN assessment, also considering that
      healthcare providers and patients frequently have a different perception of CIPN
      severity. A second major aim in clinical research is to maintain a high level of
      attention to the possible neurotoxicity of drugs more recently introduced into
      clinical practice. Preclinical studies are of pivotal importance to identify
      druggable targets for pharmacological intervention in order to prevent or limit
      CIPN.

PMID- 26197028
TI  - Prenatal Maternal Physical Activity and Stem Cells in Umbilical Cord Blood.
AB  - PURPOSE: Early life processes, through influence on fetal stem cells, affect
      postnatal and adult health outcomes. This study examines the effects of physical
      activity before and during pregnancy on stem cell counts in umbilical cord blood.
      METHODS: We isolated mononuclear cells from umbilical cord blood samples from 373
      singleton full-term pregnancies and quantified hematopoietic (CD34(+),
      CD34(+)CD38(-), and CD34(+) c-kit(+)), endothelial (CD34(+)CD133(+),
      CD34(+)CD133(+)VEGFR2(+), CD34(+)VEGFR2(+), and CD133(+)VEGFR2(+)), and putative
      breast (EpCAM(+), EpCAM(+)CD49f(+), EpCAM(+)CD49f(+)CD117(+), CD49f(+)CD24(+),
      CD24(+)CD29(+), and CD24(+)CD29(+)CD49f(+)) stem/progenitor cell subpopulations
      by flow cytometry. Information on physical activities before and during pregnancy
      was obtained from questionnaires. Weekly energy expenditure was estimated based
      on metabolic equivalent task values. RESULTS: Prepregnancy vigorous exercise was
      associated positively with levels of endothelial CD34(+)CD133(+),
      CD34(+)CD133(+)VEGFR2(+), CD34(+)VEGFR2(+), and CD133(+)VEGFR2(+ )progenitor cell
      populations (P = 0.02, P = 0.01, P = 0.001, and P = 0.003, respectively);
      positive associations were observed in samples from the first births and those
      from the second or later births. Prepregnancy moderate and light exercises and
      light exercise during the first trimester were not significantly associated with
      any stem/progenitor cell population. Light exercise during the second trimester
      was positively associated with CD34(+)VEGFR2(+) endothelial progenitor cells (P =
      0.03). In addition, levels of EpCAM(+)CD49f(+) and CD49f(+)CD24(+) breast stem
      cells were significantly lower among pregnant women who engaged in
      vigorous/moderate exercise during pregnancy (P = 0.05 and P = 0.02,
      respectively). CONCLUSIONS: Vigorous exercise before pregnancy increases the
      number of endothelial progenitor cells in umbilical cord blood and thus could
      potentially enhance endothelial function and improve cardiovascular fitness in
      the offspring. Findings of lower levels of putative breast stem cell
      subpopulations could have implications on exercise and breast cancer prevention.
      Prenatal effects of exercise on fetal stem cells warrant further studies.

PMID- 26197029
TI  - Inhaled Beta2-Agonist Increases Power Output and Glycolysis during Sprinting in
      Men.
AB  - PURPOSE: The aim of the present study was to investigate the effects of the beta2
      agonist terbutaline (TER) on power output and muscle metabolism during maximal
      sprint cycling. METHODS: In a randomized double-blind cross-over design, nine
      moderately trained men (VO2max = 4.6 +/- 0.2 L . min(-1)) conducted a 10-s cycle
      sprint after inhalation of either 15 mg of TER or placebo (PLA). A muscle biopsy
      sample was collected before and <10 s after the sprint and was analyzed for
      metabolites. RESULTS: The mean power and peak power during the sprint were 8.3%
      +/- 1.1% and 7.8% +/- 2.5% higher (P < 0.05) with TER than with PLA,
      respectively. Moreover, the net rates of glycogenolysis (6.5 +/- 0.8 vs 3.1 +/-
      0.7 mmol glucosyl units . kg dry weight(-1) . s(-1)) and glycolysis (2.4 +/- 0.2
      vs 1.6 +/- 0.2 mmol glucosyl units . kg dry weight(-1) . s(-1)) were higher (P <
      0.05) with TER than with PLA. After the sprint, adenosine triphosphate (ATP) was
      reduced with PLA (P < 0.05) but not with TER. During the sprint, there was no
      difference in the breakdown of phosphocreatine (PCr) between treatments.
      Estimated anaerobic ATP utilization was 9.2% +/- 4.0% higher (P < 0.05) with TER
      than with PLA. After the sprint, ATP in Type II fibers was lowered (P < 0.05) by
      25.7% +/- 7.3% with PLA but was not reduced with TER. Before the sprint, PCr in
      Type II fibers was 24.5% +/- 7.2% lower (P < 0.05) with TER than with PLA. With
      PLA, breakdown of PCr was 50.2% +/- 24.8% higher (P < 0.05) in Type II fibers (vs
      Type I fibers), whereas no difference was observed between fiber types with TER.
      CONCLUSION: The present study shows that a TER-induced increase in power output
      is associated with increased rates of glycogenolysis and glycolysis in skeletal
      muscles. Furthermore, as TER counteracts a reduction in ATP in Type II fibers,
      TER may postpone fatigue development in these fibers.

PMID- 26197030
TI  - Impact of Muscle Glycogen Availability on the Capacity for Repeated Exercise in
      Man.
AB  - PURPOSE: This study aims to examine whether muscle glycogen availability is
      associated with fatigue in a repeated exercise bout following short-term
      recovery. METHODS: Ten endurance-trained individuals underwent two trials in a
      repeated-measures experimental design, each involving an initial run to
      exhaustion at 70% of VO2max (Run 1) followed by a 4-h recovery and a subsequent
      run to exhaustion at 70% of VO2max (Run 2). A low-carbohydrate (L-CHO; 0.3 g . kg
      body mass(-1) . h(-1)) or high-carbohydrate (H-CHO; 1.2 g . kg body mass(-1) . h(
      1)) beverage was ingested at 30-min intervals during recovery. Muscle biopsies
      were taken upon cessation of Run 1, after recovery, and at exhaustion during Run
      2 in L-CHO (F2). In H-CHO, muscle biopsies were obtained after recovery, at the
      time point coincident with fatigue in L-CHO (F2), and at the point of fatigue
      during the subsequent exercise bout (F3). RESULTS: Run 2 was more prolonged for
      participants on H-CHO (80 +/- 16 min) than for participants on L-CHO (48 +/- 11
      min; P < 0.001). Muscle glycogen concentrations were higher at the end of
      recovery for participants on H-CHO (269 +/- 84 mmol . kg dry mass(-1)) than for
      participants on L-CHO (157 +/- 37 mmol . kg dry mass(-1); P = 0.001). The rate of
      muscle glycogen degradation during Run 2 was higher with H-CHO (3.1 +/- 1.5 mmol
      . kg dry mass(-1) . min(-1)) than with L-CHO (1.6 +/- 1.3 mmol . kg dry mass(-1)
      . min(-1); P = 0.05). The concentration of muscle glycogen was higher with H-CHO
      than with L-CHO at F2 (123 +/- 28 mmol . kg dry mass(-1); P < 0.01), but no
      differences were observed between treatments at the respective points of
      exhaustion (78 +/- 22 mmol . kg dry mass(-1) . min(-1 )for H-CHO vs 72 +/- 21
      mmol . kg dry mass(-1) . min(-1) for L-CHO). CONCLUSION: Increasing carbohydrate
      intake during short-term recovery accelerates glycogen repletion in previously
      exercised muscles and thus improves the capacity for repeated exercise. The
      availability of skeletal muscle glycogen is therefore an important factor in the
      restoration of endurance capacity because fatigue during repeated exercise is
      associated with a critically low absolute muscle glycogen concentration.

PMID- 26197032
TI  - Palladium(0)-Catalyzed Methylcyclopropanation of Norbornenes with Vinyl Bromides
      and Mechanism Study.
AB  - An unusual methylcyclopropanation from [2 + 1] cycloadditions of vinyl bromides
      to norbornenes catalyzed by Pd(OAc)2/PPh3 in the presence of CH3ONa and CH3OH has
      been established. A methylcyclopropane subunit was installed by a 3-fold domino
      procedure involving a key protonation course. Preliminary deuterium-labeling
      studies revealed that the proton came from methyl of CH3OH and also exposed an
      additional hydrogen/deuterium exchange process. These two proton-concerned
      reactions were fully chemoselective. 

PMID- 26197031
TI  - The Effect of Atorvastatin on Habitual Physical Activity among Healthy Adults.
AB  - PURPOSE: Statin therapy can result in muscle pain, cramps, and weakness that may
      limit physical activity, although reports are mixed. We conducted a randomized
      control trial to examine the effect of atorvastatin on habitual physical activity
      levels in a large sample of healthy adults. METHODS: Participants (n = 418) were
      statin-naive adults (44.0 +/- 16.1 yr (mean +/- SD)) who were randomized and
      double-blinded to 80 mg . d(-1) of atorvastatin or placebo for 6 months.
      Accelerometers were worn for 96 h before and after drug treatment. Repeated
      measures analysis tested physical activity levels after versus those before drug
      treatment among groups with age and VO2max as covariates. RESULTS: In the total
      sample, sedentary behavior increased (19.5 +/- 5.1 min . d(-1)), whereas light
      intensity (9.1 +/- 3.0 min . d(-1)) and moderate-intensity (9.7 +/- 2.8 min . d(
      1)) physical activity decreased, as did total activity counts (17.8 +/- 6.3 d *
      10(-3)) over 6 months (P < 0.01), with no differences between groups. The
      atorvastatin group increased sedentary behavior (19.8 +/- 7.4 min . d(-1)) and
      decreased light-intensity (10.7 +/- 4.3 min . d(-1)) and moderate-intensity (8.5
      +/- 4.0 min . d(-1)) physical activity (P < 0.05). On the other hand, the placebo
      group increased sedentary behavior (19.2 +/- 7.1 min . d(-1)) and decreased
      moderate-intensity (11.0 +/- 3.8 min . d(-1)) and total physical activity counts
      (-23.8 +/- 8.8 * 10(-3) d(-1)) (P < 0.05). CONCLUSIONS: Time being sedentary
      increased and physical activity levels decreased in the total sample over 6
      months of drug treatment, independent of group assignment. Our results suggest
      that statins do not influence physical activity levels any differently from
      placebo, and the lack of inclusion of a placebo condition may provide insight
      into inconsistencies in the literature.

PMID- 26197034
TI  - The Economic Lives of People with Disabilities in Vietnam.
AB  - Through a series of focus group discussions conducted in northern and central
      Vietnam, this study gives voice to the lived economic experience of families with
      disabilities and how they manage the economic challenges associated with
      disability. The dynamic of low and unstable income combined with on-going health
      care and other disability-related costs gives rise to a range of coping
      mechanisms (borrowing, reducing and foregoing expenditures, drawing upon savings
      and substituting labour) that helps to maintain living standards in the short-run
      yet threatens the longer-term welfare of both the individual with disability and
      their household. Current social protection programs were reported as not
      accessible to all and while addressing some immediate economic costs of
      disability, do not successfully meet current needs nor accommodate wider barriers
      to availing benefits. 

PMID- 26197033
TI  - Stereospecific nickel-catalyzed cross-coupling reactions of benzylic ethers and
      esters.
AB  - This Account presents the development of a suite of stereospecific alkyl-alkyl
      cross-coupling reactions employing nickel catalysts. Our reactions complement
      related nickel-catalyzed stereoconvergent cross-coupling reactions from a
      stereochemical and mechanistic perspective. Most reactions of alkyl electrophiles
      with low-valent nickel complexes proceed through alkyl radicals and thus are
      stereoablative; the correct enantioselective catalyst can favor the formation of
      one enantiomer. Our reactions, in contrast, are stereospecific. Enantioenriched
      ethers and esters are cleanly converted to cross-coupled products with high
      stereochemical fidelity. While mechanistic details are still to be refined, our
      results are consistent with a polar, two-electron oxidative addition that avoids
      the formation of radical intermediates. This reactivity is unusual for a first
      row transition metal. The cross-coupling reactions engage a range of benzylic
      ethers and esters, including methyl ethers, tetrahydropyrans, tetrahydrofurans,
      esters, and lactones. Coordination of the arene substituent to the nickel
      catalyst accelerates the reactions. Arenes with low aromatic stabilization
      energies, such as naphthalene, benzothiophene, and furan, serve as the best
      ligands and provide the highest reactivity. Traceless directing groups that
      accelerate reactions of sluggish substrates are described, providing partial
      compensation for arene coordination. Kumada, Negishi, and Suzuki reactions
      provide incorporation of a broad range of transmetalating agents. In Kumada
      coupling reactions, a full complement of Grigard reagents, including methyl, n
      alkyl, and aryl Grignard reagents, are employed. In reactions employing
      methylmagnesium iodide, ligation of the nickel catalyst by rac-BINAP or DPEphos
      provides the highest yield and stereospecificity. For all other Grignard
      reagents, Ni(dppe)Cl2 has emerged as the best catalyst. Negishi cross-coupling
      reactions employing dimethylzinc are reported as a strategy to increase the
      functional group tolerance of the reaction. We also describe Suzuki reactions
      using arylboronic esters. These reactions provided the first example in the
      series of a switch in stereochemical outcome. The reactions maintain
      stereospecificity, but reactions employing different achiral ligands provide
      opposite enantiomers of the product. Use of an N-heterocyclic carbene ligand,
      SIMes, provides inversion, consistent with our prior work in Kumada and Negishi
      coupling reactions. Use of the electron-rich phosphine PCy3, however, provides
      retention with stereospecificity, signaling a change in the mechanistic details.
      Potential applications of the reported cross-coupling reactions include the
      synthesis of medicinal agents containing the 2-arylalkane and 1,1-diarylalkane
      moieties, which are pharmacophores in medicinal chemistry. These moieties are
      found in compounds with activity against a broad range of indications, including
      cancer, heart disease, diabetes, osteoporosis, smallpox, tuberculosis, and
      insomnia. We highlight representative examples of bioactive compounds that we
      have prepared with high enantioselectivity employing our methods, as well as the
      discovery of a new anti-cancer agent. 

PMID- 26197035
TI  - Infections with Candidatus Neoehrlichia mikurensis and Cytokine Responses in 2
      Persons Bitten by Ticks, Sweden.
AB  - The prevalence of Candidatus Neoehrlichia mikurensis infection was determined in
      102 persons bitten by ticks in Sweden. Two infected women had erythematous
      rashes; 1 was co-infected with a Borrelia sp., and the other showed
      seroconversion for Anaplasma phagocytophilum. Both patients had increased levels
      of Neoehrlichia DNA and serum cytokines for several months. 

PMID- 26197036
TI  - Efficient production of xylitol from hemicellulosic hydrolysate using engineered
      Escherichia coli.
AB  - A metabolically engineered Escherichia coli has been constructed for the
      production of xylitol, one of the top 12 platform chemicals from agricultural
      sources identified by the US Department of Energy. An optimal plasmid was
      constructed to express xylose reductase from Neurospora crassa with almost no
      inclusion bodies at relatively high temperature. The phosphoenolpyruvate
      dependent glucose phosphotransferase system (ptsG) was disrupted to eliminate
      catabolite repression and allow simultaneous uptake of glucose and xylose. The
      native pathway for D-xylose catabolism in E. coli W3110 was blocked by deleting
      the xylose isomerase (xylA) and xylulose kinase (xylB) genes. The putative
      pathway for xylitol phosphorylation was also blocked by disrupting the
      phosphoenolpyruvate-dependent fructose phosphotransferase system (ptsF). The
      xylitol producing recombinant E. coli allowed production of 172.4 g L(-1) xylitol
      after 110 h of fed-batch cultivation with an average productivity of 1.57 g L(-1)
      h(-1). The molar yield of xylitol to glucose reached approximately 2.2 (mol
      xylitol mol(-1) glucose). Furthermore, the recombinant strain also produced about
      150 g L(-1) xylitol from hemicellulosic sugars in modified M9 minimal medium and
      the overall productivity was 1.40 g L(-1) h(-1), representing the highest xylitol
      concentration and productivity reported to date from hemicellulosic sugars using
      bacteria. Thus, this engineered E. coli is a candidate for the development of
      efficient industrial-scale production of xylitol from hemicellulosic hydrolysate.

PMID- 26197037
TI  - The Promise of Quantum Simulation.
AB  - Quantum simulations promise to be one of the primary applications of quantum
      computers, should one be constructed. This article briefly summarizes the history
      of quantum simulation in light of the recent result of Wang and co-workers,
      demonstrating calculation of the ground and excited states for a HeH(+) molecule,
      and concludes with a discussion of why this and other recent progress in the
      field suggest that quantum simulations of quantum chemistry have a bright future.

PMID- 26197038
TI  - Fluorescence Turn-on Enantioselective Recognition of both Chiral Acidic Compounds
      and alpha-Amino Acids by a Chiral Tetraphenylethylene Macrocycle Amine.
AB  - New chiral tetraphenylethylene (TPE) macrocycles bearing optically pure amine
      groups were synthesized and found to have a discriminating ability between the
      two enantiomers of not only chiral acidic compounds but also alpha-amino acids by
      enantioselective aggregation and aggregation-induced emission (AIE) effects. NMR
      spectra, including 2D-NOESY, disclosed that the host-guest interaction of the
      macrocycle receptor played a key role in addition to the acid-base interactions. 

PMID- 26197039
TI  - Oxidation of Half-Lantern Pt2(II,II) Compounds by Halocarbons. Evidence of
      Dioxygen Insertion into a Pt(III)-CH3 Bond.
AB  - The half-lantern compound [{Pt(bzq)(MU-N^S)}2] (1) [bzq = benzo[h]quinoline, HN^S
      = 2-mercaptopyrimidine (C4H3N2HS)] reacts with CH3I and haloforms CHX3 (X = Cl,
      Br, I) to give the corresponding oxidized diplatinum(III) derivatives
      [{Pt(bzq)(MU-N^S)X}2] (X = Cl 2a, Br 2b, I 2c). These compounds exhibit half
      lantern structures with short intermetallic distances (~2.6 A) due to Pt-Pt bond
      formation. The halogen abstraction mechanisms from the halocarbon molecules by
      the Pt2(II,II) compound 1 were investigated. NMR spectroscopic evidence using
      labeled reagents support that in the case of (13)CH3I the reaction initiates with
      an oxidative addition through an SN2 mechanism giving rise to the intermediate
      species [I(bzq)Pt(MU-N^S)2Pt(bzq)((13)CH3)}]. However, with haloforms the
      reactions proceed through a radical-like mechanism, thermally (CHBr3, CHI3) or
      photochemically (CHCl3) activated, giving rise to mixtures of species
      [X(bzq)Pt(MU-N^S)2Pt(bzq)R] (3a-c) and [X(bzq)Pt(MU-N^S)2Pt(bzq)X] (2a-c). In
      these cases the presence of O2 favors the formation of species 2 over 3.
      Transformation of 3 into 2 was possible upon irradiation with UV light. In the
      case of [I(bzq)Pt(MU-N^S)2Pt(bzq)((13)CH3)}] (3d), in the presence of O2 the
      formation of the unusual methylperoxo derivative [I(bzq)Pt(MU-N^S)2Pt(bzq)(O
      O(13)CH3)}] (4d) was detected, which in the presence of (13)CH3I rendered the
      final product [{Pt(bzq)(MU-N^S)I}2] (2c) and (13)CH3OH. 

PMID- 26197040
TI  - Colorimetric Detection of Small Molecules in Complex Matrixes via Target-Mediated
      Growth of Aptamer-Functionalized Gold Nanoparticles.
AB  - A versatile and sensitive colorimetric assay that allows the rapid detection of
      small-molecule targets using the naked eye is demonstrated. The working principle
      of the assay integrates aptamer-target recognition and the aptamer-controlled
      growth of gold nanoparticles (Au NPs). Aptamer-target interactions modulate the
      amount of aptamer strands adsorbed on the surface of aptamer-functionalized Au
      NPs via desorption of the aptamer strands when target molecules bind with the
      aptamer. Depending on the resulting aptamer coverage, Au NPs grow into
      morphologically varied nanostructures, which give rise to different colored
      solutions. Au NPs with low aptamer coverage grow into spherical NPs, which
      produce red-colored solutions, whereas Au NPs with high aptamer coverage grow
      into branched NPs, which produce blue-colored solutions. We achieved visible
      colorimetric response and nanomolar detection limits for the detection of
      ochratoxin A (1 nM) in red wine samples, as well as cocaine (1 nM) and 17beta
      estradiol (0.2 nM) in spiked synthetic urine and saliva, respectively. The
      detection limits were well within clinically and physiologically relevant ranges,
      and below the maximum food safety limits. The assay is highly sensitive,
      specific, and able to detect an array of analytes rapidly without requiring
      sophisticated equipment, making it relevant for many applications, such as high
      throughput drug and clinical screening, food sampling, and diagnostics.
      Furthermore, the assay is easily adapted as a chip-based platform for rapid and
      portable target detection. 

PMID- 26197041
TI  - Pyridine N-Oxide vs Pyridine Substrates for Rh(III)-Catalyzed Oxidative C-H Bond
      Functionalization.
AB  - The origin of the high reactivity and site selectivity of pyridine N-oxide
      substrates in O-pivaloyl hydroxamic acid-directed Rh(III)-catalyzed (4+2)
      annulation reactions with alkynes was investigated computationally. The reactions
      of the analogous pyridine derivatives were previously reported to be slower and
      to display poor site selectivity for functionalization of the C(2)-H vs the C(4)
      H bonds of the pyridine ring. The N-oxide substrates are found to be more
      reactive overall because the directing group interacts more strongly with Rh. For
      N-oxide substrates, alkyne insertion is rate-limiting and selectivity-determining
      in the reaction with a dialkyl alkyne, but C-H activation can be selectivity
      determining with other coupling partners such as terminal alkynes. The rates of
      reaction with a dialkyl alkyne at the two sites of a pyridine substrate are
      limited by two different steps: C-H activation is limiting for C(2)
      functionalization, while alkyne insertion is limiting for C(4)-functionalization.
      Consistent with the observed poor site selectivity in the reaction of a pyridine
      substrate, the overall energy barriers for functionalization of the two positions
      are nearly identical. High C(2)-selectivity in the C-H activation step of the
      reaction of the N-oxide is due to a cooperative effect of the C-H Bronsted
      acidity, the strength of the forming C-Rh bond, and intramolecular electrostatic
      interactions between the [Rh]Cp* and the heteroaryl moieties. On the other hand,
      some of these forces are in opposition in the case of the pyridine substrate, and
      C(4)-H activation is moderately favored overall. The alkyne insertion step is
      favored at C(2) over C(4) for both substrates, and this preference is largely
      influenced by electrostatic interactions between the alkyne and the heteroarene.
      Experimental results that support these calculations, including kinetic isotope
      effect studies, H/D exchange studies, and results using a substituted pyridine,
      are also described. 

PMID- 26197042
TI  - Might Pelvic Surgeons Be Unaware of Their Surgical Failures? Patient Reporting
      and Perceptions After Failed Incontinence or Pelvic Organ Prolapse Surgery.
AB  - : Prior studies suggest that pelvic organ prolapse (POP) and stress urinary
      incontinence (SUI) may recur following surgery in 20% or more of patients.
      Despite these numbers, we have anecdotally found that some surgeons performing
      pelvic floor reconstruction feel their success rates exceed these figures. Based
      on our experience, we hypothesized that significant numbers of patients with
      recurrent POP or SUI following prior surgery do not return or notify their
      original surgeon of their recurrence. We also aimed to identify reasons why the
      patient was seeking care elsewhere. METHODS: We investigated patients presenting
      to a tertiary referral center urogynecologic practice with recurrence after prior
      POP or SUI surgery over a 2-year period. Data were collected using an
      institutional review board-approved 15-item questionnaire and after 2 years were
      analyzed. RESULTS: We found that 16 (31%) of 51 patients did not notify their
      primary surgeon of surgical failure. Of these patients, roughly half (9/16) did
      not return because of moving to a different area of the country, changing their
      insurance, or their prior physician retiring. Despite the surgical failures, of
      all patients presenting to our clinic, very few stated they had a poor
      relationship with their prior surgeon (6%); however, a large majority (63%) did
      not think that their primary surgeon could fix their problem. CONCLUSIONS:
      Roughly one third of patients who suffer from recurrence after POP or SUI surgery
      do not notify their original surgeon. This may artificially inflate a clinician's
      perceived success rate of pelvic floor repair.

PMID- 26197043
TI  - Ketamine affects in vitro differentiation of monocyte into immature dendritic
      cells.
AB  - BACKGROUND: Monocytes (MOs) have the unique ability to differentiate into
      immature dendritic cells (iDCs) (MO->iDC) under the influence of interleukin-4
      and granulocyte-monocyte colony-stimulating factor (IL-4&GM-CSF). In this study,
      the authors investigated the influence of ketamine on the process of MO->iDC.
      METHODS: iDCs were cultured from MO obtained from 36 subjects in the presence of
      IL-4 and GM-CSF and ketamine at 100, 10, and 1 MUg/ml for 5 days. In some of the
      experiments, the authors used nonspecific N-methyl-D-aspartate (NMDA) receptor
      antagonist MK-801, NMDA, or a neutralizing antibody for transforming growth
      factor beta (TGFbeta). The expression of surface markers and functional assays
      were used to assess the effect of ketamine on IL-4&GM-CSF-stimulated MO. IL-4&GM
      CSF-stimulated MO's supernatants were assessed for cytokine levels. RESULTS:
      Ketamine at 10 MUg/ml, and higher concentrations, diminished the expression of
      CD1a on IL-4&GM-CSF-stimulated MO and retarded both their ability to process DQ
      ovalbumin and mixed lymphocyte reaction stimulation. The addition of ketamine to
      IL-4&GM-CSF-differentiated MO resulted in the persistent expression of CD14 and
      unchanged expression of CD86 and CD206. The phagocytic abilities of IL-4&GM-CSF
      differentiated MO were not changed by ketamine. MK-801, a nonselective NMDA
      agonist, mimicked ketamine's effect on MO->iDC differentiation. Adding exogenous
      NMDA to IL-4&GM-CSF-stimulated MO in the presence of ketamine partially restored
      the level of CD1a. TGFbeta was elevated in supernatants of IL-4&GM-CSF-stimulated
      MO in the presence of ketamine. Adding neutralizing TGFbeta antibody or TGFbetaR1
      blocker (SB431542) resulted in the full recovery of MO->iDC, despite the presence
      of ketamine. CONCLUSIONS: Ketamine diminishes the process of MO->iDC in vitro.
      This is mediated via NMDA-dependent mechanisms and TGFbeta.

PMID- 26197045
TI  - Teaching whole body point-of-care ultrasound: advancing the skills of tomorrow's
      anesthesiologists.

PMID- 26197046
TI  - Real-time Three-dimensional Echocardiographic Assessment of Rheumatic Mitral
      Valve Stenosis.

PMID- 26197047
TI  - Heterogeneity of Borrelia burgdorferi Sensu Stricto Population and Its
      Involvement in Borrelia Pathogenicity: Study on Murine Model with Specific
      Emphasis on the Skin Interface.
AB  - Lyme disease is a multisystemic disorder caused by B. burgdorferi sl. The
      molecular basis for specific organ involvement is poorly understood. The skin
      plays a central role in the development of Lyme disease as the entry site of B.
      burgdorferi in which specific clones are selected before dissemination. We
      compared the skin inflammatory response (antimicrobial peptides, cytokines and
      chemokines) elicited by spirochete populations recovered from patients presenting
      different clinical manifestations. Remarkably, these spirochete populations
      induced different inflammatory profiles in the skin of C3H/HeN mice. As
      spirochete population transmitted into the host skin is heterogeneous, we
      isolated one bacterial clone from a population recovered from a patient with
      neuroborreliosis and compared its virulence to the parental population. This
      clone elicited a strong cutaneous inflammatory response characterized by MCP-1,
      IL-6 and antimicrobial peptides induction. Mass spectrometry of this clone
      revealed 110 overexpressed proteins when compared with the parental population.
      We further focused on the expression of nine bacterial surface proteins. bb0347
      coding for a protein that interacts with host fibronectin, allowing bacterial
      adhesion to vascular endothelium and extracellular matrix, was found to be
      induced in host skin with another gene bb0213 coding for a hypothetical protein.
      These findings demonstrate the heterogeneity of the B. burgdorferi ss population
      and the complexity of the interaction involved early in the skin.

PMID- 26197048
TI  - Cutaneous Legionella longbeachae Infection in Immunosuppressed Woman, United
      Kingdom.
AB  - We report a rare case of cutaneous Legionella longbeachae infection in a patient
      receiving long-term corticosteroids for immune thrombocytopenia. Such infections
      cannot be identified by using Legionella urinary antigen testing but are commonly
      seen after exposure to commercial potting compost, particularly in
      immunocompromised patients. 

PMID- 26197049
TI  - Increased Resting-State Functional Connectivity in the Cingulo-Opercular
      Cognitive-Control Network after Intervention in Children with Reading
      Difficulties.
AB  - Dyslexia, or reading difficulty, is characterized by slow, inaccurate reading
      accompanied by executive dysfunction. Reading training using the Reading
      Acceleration Program improves reading and executive functions in both children
      with dyslexia and typical readers. This improvement is associated with increased
      activation in and functional connectivity between the anterior cingulate cortex,
      part of the cingulo-opercular cognitive-control network, and the fusiform gyrus
      during a reading task after training. The objective of the current study was to
      determine whether the training also has an effect on functional connectivity of
      the cingulo-opercular and fronto-parietal cognitive-control networks during rest
      in children with dyslexia and typical readers. Fifteen children with reading
      difficulty and 17 typical readers (8-12 years old) were included in the study.
      Reading and executive functions behavioral measures and resting-state functional
      magnetic resonance imaging data were collected before and after reading training.
      Imaging data were analyzed using a graphical network-modeling tool. Both reading
      groups had increased reading and executive-functions scores after training, with
      greater gains among the dyslexia group. Training may have less effect on
      cognitive control in typical readers and a more direct effect on the visual area,
      as previously reported. Statistical analysis revealed that compared to typical
      readers, children with reading difficulty had significantly greater functional
      connectivity in the cingulo-opercular network after training, which may
      demonstrate the importance of cognitive control during reading in this
      population. These results support previous findings of increased error-monitoring
      activation after reading training in children with dyslexia and confirm greater
      gains with training in this group. 

PMID- 26197050
TI  - Identification of Interactions between Abscisic Acid and Ribulose-1,5
      Bisphosphate Carboxylase/Oxygenase.
AB  - Abscisic acid ((+)-ABA) is a phytohormone involved in the modulation of
      developmental processes and stress responses in plants. A chemical proteomics
      approach using an ABA mimetic probe was combined with in vitro assays, isothermal
      titration calorimetry (ITC), x-ray crystallography and in silico modelling to
      identify putative (+)-ABA binding-proteins in crude extracts of Arabidopsis
      thaliana. Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) was
      identified as a putative ABA-binding protein. Radiolabelled-binding assays
      yielded a Kd of 47 nM for (+)-ABA binding to spinach Rubisco, which was validated
      by ITC, and found to be similar to reported and experimentally derived values for
      the native ribulose-1,5-bisphosphate (RuBP) substrate. Functionally, (+)-ABA
      caused only weak inhibition of Rubisco catalytic activity (Ki of 2.1 mM), but
      more potent inhibition of Rubisco activation (Ki of ~ 130 MUM). Comparative
      structural analysis of Rubisco in the presence of (+)-ABA with RuBP in the active
      site revealed only a putative low occupancy (+)-ABA binding site on the surface
      of the large subunit at a location distal from the active site. However, subtle
      distortions in electron density in the binding pocket and in silico docking
      support the possibility of a higher affinity (+)-ABA binding site in the RuBP
      binding pocket. Overall we conclude that (+)-ABA interacts with Rubisco. While
      the low occupancy (+)-ABA binding site and weak non-competitive inhibition of
      catalysis may not be relevant, the high affinity site may allow ABA to act as a
      negative effector of Rubisco activation.

PMID- 26197052
TI  - Production of lysozyme and lysozyme-superoxide dismutase dimers bound by a
      ditryptophan cross-link in carbonate radical-treated lysozyme.
AB  - Despite extensive investigation of the irreversible oxidations undergone by
      proteins in vitro and in vivo, the products formed from the oxidation of Trp
      residues remain incompletely understood. Recently, we characterized a
      ditryptophan cross-link produced by the recombination of hSOD1-tryptophanyl
      radicals generated from attack of the carbonate radical produced during the
      bicarbonate-dependent peroxidase activity of the enzyme. Here, we examine whether
      the ditryptophan cross-link is produced by the attack of the carbonate radical on
      proteins other than hSOD1. To this end, we treated hen egg white lysozyme with
      photolytically and enzymatically generated carbonate radical. The radical yields
      were estimated and the lysozyme modifications were analyzed by SDS-PAGE, western
      blot, enzymatic activity and MS/MS analysis. Lysozyme oxidation by both systems
      resulted in its inactivation and dimerization. Lysozyme treated with the
      photolytic system presented monomers oxidized to hydroxy-tryptophan at Trp(28)
      and Trp(123) and N-formylkynurenine at Trp(28), Trp(62) and Trp(123). Lysozyme
      treated with the enzymatic system rendered monomers oxidized to N
      formylkynurenine at Trp(28). The dimers were characterized as lysozyme-Trp(28)
      Trp(28)-lysozyme and lysozyme-Trp(28)-Trp(32)-hSOD1. The results further
      demonstrate that the carbonate radical is prone to causing biomolecule cross
      linking and hence, may be a relevant player in pathological mechanisms. The
      possibility of exploring the formation of ditryptophan cross-links as a carbonate
      radical biomarker is discussed. 

PMID- 26197051
TI  - Abnormal Social Reward Responses in Anorexia Nervosa: An fMRI Study.
AB  - Patients with anorexia nervosa (AN) display impaired social interactions,
      implicated in the development and prognosis of the disorder. Importantly, social
      behavior is modulated by reward-based processes, and dysfunctional at-brain-level
      reward responses have been involved in AN neurobiological models. However, no
      prior evidence exists of whether these neural alterations would be equally
      present in social contexts. In this study, we conducted a cross-sectional social
      judgment functional magnetic resonance imaging (fMRI) study of 20 restrictive
      subtype AN patients and 20 matched healthy controls. Brain activity during
      acceptance and rejection was investigated and correlated with severity measures
      (Eating Disorder Inventory -EDI-2) and with personality traits of interest known
      to modulate social behavior (The Sensitivity to Punishment and Sensitivity to
      Reward Questionnaire). Patients showed hypoactivation of the dorsomedial
      prefrontal cortex (DMPFC) during social acceptance and hyperactivation of visual
      areas during social rejection. Ventral striatum activation during rejection was
      positively correlated in patients with clinical severity scores. During
      acceptance, activation of the frontal opercula-anterior insula and
      dorsomedial/dorsolateral prefrontal cortices was differentially associated with
      reward sensitivity between groups. These results suggest an abnormal motivational
      drive for social stimuli, and involve overlapping social cognition and reward
      systems leading to a disruption of adaptive responses in the processing of social
      reward. The specific association of reward-related regions with clinical and
      psychometric measures suggests the putative involvement of reward structures in
      the maintenance of pathological behaviors in AN.

PMID- 26197053
TI  - Correction: The Rationale for Using Rifabutin in the Treatment of MDR and XDR
      Tuberculosis Outbreaks.

PMID- 26197054
TI  - Fluoxetine enhanced neurogenesis is not translated to functional outcome in
      stroke rats.
AB  - Fluoxetine is widely used in clinical practice. It regulates hippocampal
      neurogenesis, however, the effect of fluoxetine on neurogenesis in the
      subventricular zone (SVZ) remains controversial. We aimed to study the effect of
      fluoxetine on neurogenesis in the SVZ and subgranular zone (SGZ) of dentate gyrus
      (DG) in relation to behavioral recovery after stroke in rats. Adult male Wistar
      rats were randomly assigned to four groups: sham-operated rats, sham-operated
      rats treated with fluoxetine, rats subjected to cerebral ischemia, and rats with
      ischemia treated with fluoxetine. Fluoxetine was orally administrated starting 1
      week after ischemia, with a dose of 16mg/kg/day for 3 weeks. Focal cerebral
      ischemia was induced by intracranial injection of vasoconstrictive peptide
      endothelin-1(ET-1). Behavioral recovery was evaluated on post-stroke days 29-31
      after which the survival rate and fate of proliferating cells in the SVZ and DG
      were measured by immunohistochemistry. The production of neuroblasts in both the
      SVZ and DG was significantly increased after stroke. Chronic post-stroke
      fluoxetine treatment increased the dendritic complexity of newborn dentate
      granule cells. However, fluoxetine treatment did not influence the survival or
      differentiation of newly generated cells. Neither fluoxetine treatment improved
      sensorimotor recovery following focal cerebral ischemia. 

PMID- 26197055
TI  - Comparative gait initiation kinematics between simulated unilateral and bilateral
      ankle hypomobility: Does bilateral constraint improve speed performance?
AB  - Improvement of motor performance in unilateral upper limb motor disability has
      been shown when utilizing inter-limb coupling strategies during physical
      rehabilitation. This suggests that 'default' bilateral central motor commands are
      facilitated. Here, we tested whether this bilateral motor control principle may
      be generalized to the lower limbs during gait initiation, which involves
      alternate bilateral actions. Disability was simulated by strapping to produce
      ankle hypomobility. Healthy adult subjects initiated gait at a self-paced speed
      with no ankle constraint (control), or with the stance, swing or bilateral ankles
      strapped. The duration of the anticipatory postural adjustments lengthened and
      the center of mass instantaneous progression velocity at foot-off decreased when
      the ankle was strapped. During the step execution phase, progression velocity at
      foot-contact was higher when both ankles were strapped compared to unilateral
      strapping of the stance ankle. These findings suggest that bilateral central
      motor commands are favored during walking tasks. Indeed, unilateral constraint of
      the stance ankle should compel the central nervous system to adapt specific
      commands to the constraint and normal sides whereas the 'default' bilateral motor
      commands would be utilized when both ankles are strapped leading to better
      kinematics performance. Bilateral in-phase upper limb coordination and bilateral
      alternating lower limb locomotor movements may share similar control mechanisms. 

PMID- 26197056
TI  - Antimicrobial-Resistant Bacterial Populations and Antimicrobial Resistance Genes
      Obtained from Environments Impacted by Livestock and Municipal Waste.
AB  - This study compared the populations of antimicrobial-resistant bacteria and the
      repertoire of antimicrobial resistance genes in four environments: effluent of
      three municipal wastewater treatment facilities, three cattle feedlot runoff
      catchment ponds, three swine waste lagoons, and two "low impact" environments (an
      urban lake and a relict prairie). Multiple liquid and solid samples were
      collected from each environment. The prevalences and concentrations of
      antimicrobial-resistant (AMR) Gram-negative (Escherichia coli and Salmonella
      enterica) and Gram-positive (enterococci) bacteria were determined from
      individual samples (n = 174). The prevalences of 84 antimicrobial resistance
      genes in metagenomic DNA isolated from samples pooled (n = 44) by collection
      date, location, and sample type were determined. The prevalences and
      concentrations of AMR E. coli and Salmonella were similar among the livestock and
      municipal sample sources. The levels of erythromycin-resistant enterococci were
      significantly higher in liquid samples from cattle catchment ponds and swine
      waste lagoons than in liquid samples from municipal wastewater treatment
      facilities, but solid samples from these environments did not differ
      significantly. Similarly, trimethoprim/sulfamethoxazole-resistant E. coli
      concentrations were significantly higher in swine liquid than in municipal liquid
      samples, but there was no difference in solid samples. Multivariate analysis of
      the distribution of antimicrobial resistance genes using principal coordinate
      analysis showed distinct clustering of samples with livestock (cattle and swine),
      low impact environment and municipal samples forming three separate clusters. The
      numbers of class A beta-lactamase, class C beta-lactamase, and fluoroquinolone
      resistance genes detected were significantly higher (P < 0.05) in municipal
      samples than in cattle runoff or swine lagoon samples. In conclusion, we report
      that AMR is a very widespread phenomenon and that similar prevalences and
      concentrations of antimicrobial-resistant bacteria and antimicrobial resistance
      genes exist in cattle, human, and swine waste streams, but a higher diversity of
      antimicrobial resistance genes are present in treated human waste discharged from
      municipal wastewater treatment plants than in livestock environments. 

PMID- 26197057
TI  - Monitoring Cerebrovascular Reactivity through the Use of Arterial Spin Labeling
      in Patients with Moyamoya Disease.
AB  - PURPOSE: To assess arterial spin labeling in the identification of impaired
      cerebrovascular reactivity in patients with moyamoya disease. MATERIALS AND
      METHODS: The institutional review board approved this prospective study, and
      written informed consent was obtained from all patients. A prospective study was
      conducted in 78 subjects with moyamoya disease (of whom 31 underwent unilateral
      direct arterial anastomosis). The concordance between the cerebrovascular
      reactivity index values from arterial spin labeling and single photon emission
      computed tomography (SPECT) was assessed by using Bland-Altman analysis, and the
      area under the receiver operating characteristic curve was used to evaluate the
      diagnostic accuracy of arterial spin labeling to depict impaired cerebrovascular
      reactivity (in which the cerebrovascular reactivity index value is less than 0%
      on SPECT images). RESULTS: The cerebrovascular reactivity index from arterial
      spin labeling had a lower value than that from SPECT (mean difference, -4.2%).
      The area under the receiver operating characteristic curve for arterial spin
      labeling in the detection of impaired cerebrovascular reactivity was at least
      0.85. On the anastomotic side, a significant increase was found between the
      cerebrovascular reactivity index values on arterial spin labeling images obtained
      preoperatively and those obtained 6 months after surgery, as well as on SPECT
      images (mean +/- standard deviation values of cerebrovascular reactivity index
      increased by 5.9% +/- 10.9 and 3.0% +/- 6.3 for arterial spin labeling and SPECT,
      respectively). CONCLUSION: Arterial spin labeling has excellent performance in
      the identification of impaired cerebrovascular reactivity in patients with
      moyamoya disease, and it has the potential to serve as a noninvasive imaging tool
      to monitor cerebrovascular reactivity in patients with moyamoya disease.

PMID- 26197058
TI  - Hepato-Nephrocitic System: A Novel Model of Biomarkers for Analysis of the
      Ecology of Stress in Environmental Biomonitoring.
AB  - Bombus presents a serious global decline of populations and even loss of species.
      This phenomenon is complex and multifactorial: environmental degradation due to
      increasing cultivation and grazing areas, indiscriminate use of agrochemicals,
      and a plethora of xenobiotics daily discharged in the environment. We proposed
      that bees have an integrated cell system, which ensures protection against
      chemical stressors up to a certain limit. Therefore, this hypothesis was tested,
      exposing workers of Bombus morio to cadmium, a harmful trace metal nowadays
      widespread in our society. The workers were kept in BOD (26 degrees C, RH 70%, in
      the dark), fed ad libitum, and divided into a control group (n = 20) and an
      experimental group (n = 20). For the first group, we offered 2 mL of distilled
      water; for the experimental groups, 2 mL of cadmium at 1 ppb. In relation to the
      control group, exposed bees showed that their fat body and hemocytes responded in
      synchronization with pericardial cells in a topographical and temporal cascade of
      events, where the fat body is the first barrier against xenobiotics, followed by
      pericardial cells. The immune cells participate throughout the process. To this
      system, we proposed the name of hepato-nephrocitic system (HNS), which may
      explain many phenomena that remain unclear in similar research with Apis
      mellifera and other species of bees, as shown in this paper. The bee's HNS is a
      system of highly responsive cells to toxicants, considered a novel parameter for
      the study of the ecology of stress applied in environmental management.

PMID- 26197059
TI  - Spatiotemporal analysis and human exposure assessment on polycyclic aromatic
      hydrocarbons in indoor air, settled house dust, and diet: A review.
AB  - This review summarizes the published literature on the presence of polycyclic
      aromatic hydrocarbons (PAH) in indoor air, settled house dust, and food, and
      highlights geographical and temporal trends in indoor PAH contamination. In both
      indoor air and dust, SigmaPAH concentrations in North America have decreased over
      the past 30 years with a halving time of 6.7+/-1.9years in indoor air and 5.0+/
      2.3 years in indoor dust. In contrast, indoor PAH concentrations in Asia have
      remained steady. Concentrations of SigmaPAH in indoor air are significantly
      (p<0.01) higher in Asia than North America. In studies recording both vapor and
      particulate phases, the global average concentration in indoor air of SigmaPAH
      excluding naphthalene is between 7 and 14,300 ng/m(3). Over a similar period, the
      average SigmaPAH concentration in house dust ranges between 127 to 115,817ng/g.
      Indoor/outdoor ratios of atmospheric concentrations of SigmaPAH have declined
      globally with a half-life of 6.3+/-2.3 years. While indoor/outdoor ratios for
      benzo[a]pyrene toxicity equivalents (BaPeq) declined in North America with a half
      life of 12.2+/-3.2 years, no significant decline was observed when data from all
      regions were considered. Comparison of the global database, revealed that I/O
      ratios for SigmaPAH (average=4.3+/-1.3), exceeded significantly those of BaPeq
      (average=1.7+/-0.4) in the same samples. The significant decline in global I/O
      ratios suggests that indoor sources of PAH have been controlled more effectively
      than outdoor sources. Moreover, the significantly higher I/O ratios for SigmaPAH
      compared to BaPeq, imply that indoor sources of PAH emit proportionally more of
      the less carcinogenic PAH than outdoor sources. Dietary exposure to PAH ranges
      from 137 to 55,000 ng/day. Definitive spatiotemporal trends in dietary exposure
      were precluded due to relatively small number of relevant studies. However,
      although reported in only one study, PAH concentrations in Chinese diets exceeded
      those in diet from other parts of the world, a pattern consistent with the
      spatial trends observed for concentrations of PAH in indoor air. Evaluation of
      human exposure to SigmaPAH via inhalation, dust and diet ingestion, suggests that
      while intake via diet and inhalation exceeds that via dust ingestion; all three
      pathways contribute and merit continued assessment.

PMID- 26197060
TI  - Characterizing multi-pollutant air pollution in China: Comparison of three air
      quality indices.
AB  - Multi-pollutant air pollution (i.e., several pollutants reaching very high
      concentrations simultaneously) frequently occurs in many regions across China.
      Air quality index (AQI) is used worldwide to inform the public about levels of
      air pollution and associated health risks. The current AQI approach used in China
      is based on the maximum value of individual pollutants, and does not consider the
      combined health effects of exposure to multiple pollutants. In this study, two
      novel alternative indices--aggregate air quality index (AAQI) and health-risk
      based air quality index (HAQI)--were calculated based on data collected in six
      megacities of China (Beijing, Shanghai, Guangzhou, Shjiazhuang, Xi'an, and Wuhan)
      during 2013 to 2014. Both AAQI and HAQI take into account the combined health
      effects of various pollutants, and the HAQI considers the exposure (or
      concentration)-response relationships of pollutants. AAQI and HAQI were compared
      to AQI to examine the effectiveness of the current AQI in characterizing multi
      pollutant air pollution in China. The AAQI and HAQI values are higher than the
      AQI on days when two or more pollutants simultaneously exceed the Chinese Ambient
      Air Quality Standards (CAAQS) 24-hour Grade II standards. The results of the
      comparison of the classification of risk categories based on the three indices
      indicate that the current AQI approach underestimates the severity of health risk
      associated with exposure to multi-pollutant air pollution. For the AQI-based risk
      category of 'unhealthy', 96% and 80% of the days would be 'very unhealthy' or
      'hazardous' if based on AAQI and HAQI, respectively; and for the AQI-based risk
      category of 'very unhealthy', 67% and 75% of the days would be 'hazardous' if
      based on AAQI and HAQI, respectively. The results suggest that the general
      public, especially sensitive population groups such as children and the elderly,
      should take more stringent actions than those currently suggested based on the
      AQI approach during high air pollution events. Sensitivity studies were conducted
      to examine the assumptions used in the AAQI and HAQI approaches. Results show
      that AAQI is sensitive to the choice of pollutant irrelevant constant. HAQI is
      sensitive to the choice of both threshold values and pollutants included in total
      risk calculation.

PMID- 26197061
TI  - Quality of life after surgery for rectal cancer: a systematic review of
      comparisons with the general population.
AB  - Rectal cancer treatments may impact negatively on patients' bowel and sexual
      functions and, in turn, on health-related quality of life. Information on the
      likely effects of treatment is essential in order to facilitate the care process
      and the adaptation of patients to their condition. Studies that report on the
      comparison between rectal cancer patients and the general population are a useful
      source of this evidence, providing elements to aid in answering questions such as
      'is my life going to be the same as before?' In this article, the authors have
      systematically reviewed articles published in the last 6 years that report on the
      comparison between rectal patients' and the general population's health-related
      quality of life. Sixteen out of 645 articles were included. The results are
      summarized and critically discussed. 

PMID- 26197062
TI  - A New Route to Liposil Formation by an Interfacial Sol-Gel Process Confined by
      Lipid Bilayer.
AB  - We report a new and simple approach to prepare a class of silica-reinforced
      liposomes with hybrid core-shell nanostructures. The amphiphilic natural
      structure of lipids was exploited to sequester hydrophobic molecules, namely
      precursor TEOS and pyrene, in the hydrophobic midplane of liposomal bilayer
      assemblies in the aqueous phase. Subsequent interfacial hydrolysis of TEOS at the
      bilayer/water interface and ensuing condensation within the hydrophobic
      interstices of the lipid bilayer drives silica formation in situ, producing a
      novel class of silica-lipid hybrid liposils. Structural characterization by
      scanning- and transmission electron microscopy confirm that the liposils so
      generated preserve closed topologies and size-monodipersity of the parent
      lecithin liposomes, and DSC-TGA and XRD measurements provide evidence for the
      silica coating. Monitoring fluorescence measurements using embedded pyrene yield
      detailed information on microenvironment changes, which occur during sol-gel
      process and shed light on the structural evolution during silica formation. We
      envisage that liposils formed by this simple, new approach, exploiting the
      hydrophobic core of the lipid bilayer to spatially localize silica-forming
      precursors enables preparation of stable liposils exhibiting capacity for cargo
      encapsulation, bicompatibility, and fluorescence monitoring, more generally
      opening a window for construction of stable, functional hybrid materials. 

PMID- 26197063
TI  - Anxiety and depressive symptoms among patients infected with human
      immunodeficiency virus in South Korea.
AB  - Patients infected with human immunodeficiency virus (HIV) may develop mental
      health problems such as anxiety and depression, which negatively impact of
      disease progression. We investigated factors associated with the prevalence of
      anxiety and depression symptoms among HIV-infected patients in Korea. A total of
      840 HIV-infected patients who participated in the Korea HIV/AIDS Cohort Study
      from 2006 to 2012 were evaluated. Socio-demographic, epidemiologic, and clinical
      variables were obtained through standardized questionnaires. The State-Trait
      Anxiety Inventory and Beck Depression Inventory were used to assess the symptoms
      of anxiety and depression. Multiple logistic regression analyses were performed
      to identify factors associated with symptoms of anxiety and depression. The
      prevalence of anxiety and depressive symptoms among HIV-infected patients was 32%
      and 36%, respectively. Ex-smoker and persistent symptoms for more than one week
      within the past six months and diagnosis of HIV infection within one year were
      associated with increased anxiety symptoms (odds ratio [OR] 1.71, 95% confidence
      interval [CI] 1.09-2.69; OR 1.52, 95% CI 1.09-2.11; OR 1.49, 95% CI 1.02-2.20)
      and current smoking and persistent symptoms were also associated with increased
      depressive symptoms (OR 2.10, 95% CI 1.31-3.30; OR 1.87, 95% CI 1.25-2.79).
      Marital status, current smoking, current drinking, and persistent symptoms were
      associated with both increased anxiety and depressive symptoms (OR 1.75, 95% CI
      1.07-2.88; OR 1.66, 95% CI 1.06-2.61; OR 1.88, 95% CI 1.18-2.99). The prevalence
      of anxiety and depressive symptoms among HIV-infected patients is higher than
      those estimated for the general population. This study shows the necessity to
      evaluate symptoms of anxiety and depression and suggest psychological support for
      HIV-infected patients who smoke or have persistent symptoms or have sexual
      partner or drink. 

PMID- 26197064
TI  - A New Proof of the Expected Frequency Spectrum under the Standard Neutral Model.
AB  - The sample frequency spectrum is an informative and frequently employed approach
      for summarizing DNA variation data. Under the standard neutral model the
      expectation of the sample frequency spectrum has been derived by at least two
      distinct approaches. One relies on using results from diffusion approximations to
      the Wright-Fisher Model. The other is based on Polya urn models that correspond
      to the standard coalescent model. A new proof of the expected frequency spectrum
      is presented here. It is a proof by induction and does not require diffusion
      results and does not require the somewhat complex sums and combinatorics of the
      derivations based on urn models. 

PMID- 26197065
TI  - A Small-Volume, Low-Cost, and Versatile Continuous Culture Device.
AB  - BACKGROUND: Continuous culture devices can be used for various purposes such as
      establishing reproducible growth conditions or maintaining cell populations under
      a constant environment for long periods. However, commercially available
      instruments are expensive, were not designed to handle small volumes in the
      milliliter range, and can lack the flexibility required for the diverse
      experimental needs found in several laboratories. METHODOLOGY/PRINCIPAL FINDINGS:
      We developed a versatile continuous culture system and provide detailed
      instructions as well as a graphical user interface software for potential users
      to assemble and operate their own instrument. Three culture chambers can be
      controlled simultaneously with the proposed configuration, and all components are
      readily available from various sources. We demonstrate that our continuous
      culture device can be used under different modes, and can easily be programmed to
      behave either as a turbidostat or chemostat. Addition of fresh medium to the
      culture vessel can be controlled by a real-time feedback loop or simply
      calibrated to deliver a defined volume. Furthermore, the selected light-emitting
      diode and photodetector enable the use of phenol red as a pH indicator, which can
      be used to indirectly monitor the bulk metabolic activity of a cell population
      rather than the turbidity. CONCLUSIONS/SIGNIFICANCE: This affordable and
      customizable system will constitute a useful tool in many areas of biology such
      as microbial ecology as well as systems and synthetic biology.

PMID- 26197067
TI  - Diagnostic Accuracy of the Cognitive State Test in the Detection of Dementia
      Among Iranian Older Adults.
AB  - Dementia screening tests need to have acceptable sensitivity and specificity. The
      current study aimed to determine the cutoff point of the Persian Cognitive State
      Test (P-COST) and test its diagnostic accuracy. The study was conducted using the
      known-groups method. A purposive sample of 50 patients with dementia and 150
      older adults without dementia was recruited in Kashan, Iran. The reference
      standard included clinical interviewing and findings of a computerized tomography
      scan. The P-COST was the index test. Mean P-COST scores of the two groups
      differed significantly (p < 0.001). The P-COST is a sensitive and precise test
      for assessing cognitive state and thus can be used for dementia screening and
      monitoring of older adults' health.

PMID- 26197066
TI  - Family-Based Benchmarking of Copy Number Variation Detection Software.
AB  - The analysis of structural variants, in particular of copy-number variations
      (CNVs), has proven valuable in unraveling the genetic basis of human diseases.
      Hence, a large number of algorithms have been developed for the detection of CNVs
      in SNP array signal intensity data. Using the European and African HapMap trio
      data, we undertook a comparative evaluation of six commonly used CNV detection
      software tools, namely Affymetrix Power Tools (APT), QuantiSNP, PennCNV, GLAD, R
      gada and VEGA, and assessed their level of pair-wise prediction concordance. The
      tool-specific CNV prediction accuracy was assessed in silico by way of intra
      familial validation. Software tools differed greatly in terms of the number and
      length of the CNVs predicted as well as the number of markers included in a CNV.
      All software tools predicted substantially more deletions than duplications.
      Intra-familial validation revealed consistently low levels of prediction accuracy
      as measured by the proportion of validated CNVs (34-60%). Moreover, up to 20% of
      apparent family-based validations were found to be due to chance alone. Software
      using Hidden Markov models (HMM) showed a trend to predict fewer CNVs than
      segmentation-based algorithms albeit with greater validity. PennCNV yielded the
      highest prediction accuracy (60.9%). Finally, the pairwise concordance of CNV
      prediction was found to vary widely with the software tools involved. We
      recommend HMM-based software, in particular PennCNV, rather than segmentation
      based algorithms when validity is the primary concern of CNV detection. QuantiSNP
      may be used as an additional tool to detect sets of CNVs not detectable by the
      other tools. Our study also reemphasizes the need for laboratory-based
      validation, such as qPCR, of CNVs predicted in silico. 

PMID- 26197068
TI  - Effects of Physical Environment on Health and Behaviors of Residents With
      Dementia in Long-Term Care Facilities: A Longitudinal Study.
AB  - The challenges in investigating the effects of the physical environment on
      residents with dementia include having a sample of comparable study groups and a
      lack of long-term follow-up evaluation. The current study attempted to address
      these two challenges by carefully matching residents and analyzing long-term
      measurement data. The aim of the study was to examine whether residents with
      dementia (N = 12) living in a traditional large-scale setting or a small-scale,
      home-like setting exhibit any difference in health and behaviors over time.
      Physical environmental assessment of the two care facilities was conducted using
      the Therapeutic Environment Screening Survey for Nursing Homes. Residents'
      behavioral assessments were performed using three tools at three assessments over
      a period of 1 year: (a) Multidimensional Observation Scale for Elderly Subjects,
      (b) Minimum Data Set, and (c) Dementia Care Mapping. The results suggest that
      older adults with dementia can have increased social interaction and engagement
      with the support of an optimal physical environment.

PMID- 26197070
TI  - This Month's Offerings: Why Are They Important?

PMID- 26197069
TI  - Precise Classification of Cervical Carcinomas Combined with Somatic Mutation
      Profiling Contributes to Predicting Disease Outcome.
AB  - INTRODUCTION: Squamous cell carcinoma (SCC), adenocarcinoma (AC), and
      adenosquamous carcinoma (ASC) are the most common histological subtypes of
      cervical cancer. Differences in the somatic mutation profiles of these subtypes
      have been suggested. We investigated the prevalence of somatic hot-spot mutations
      in three well-defined cohorts of SCC, AC, and ASC and determined the additional
      value of mutation profiling in predicting disease outcome relative to well
      established prognostic parameters. MATERIALS AND METHODS: Clinicopathological
      data were collected for 301 cervical tumors classified as SCC (n=166), AC (n=55),
      or ASC (n=80). Mass spectrometry was used to analyze 171 somatic hot-spot
      mutations in 13 relevant genes. RESULTS: In 103 (34%) tumors, 123 mutations were
      detected (36% in SCC, 38% in AC, and 28% in ASC), mostly in PIK3CA (20%) and KRAS
      (7%). PIK3CA mutations occurred more frequently in SCC than AC (25% vs. 11%,
      P=0.025), whereas KRAS mutations occurred more frequently in AC than SCC (24% vs.
      3%, P<0.001) and ASC (24% vs. 3%, P<0.001). A positive mutation status correlated
      with worse disease-free survival (HR 1.57, P=0.043). In multivariate analysis,
      tumor diameter, parametrial infiltration, and lymph node metastasis, but not the
      presence of a somatic mutation, were independent predictors of survival.
      CONCLUSION: Potentially targetable somatic mutations occurred in 34% of cervical
      tumors with different distributions among histological subtypes. Precise
      classification of cervical carcinomas in combination with mutation profiling is
      valuable for predicting disease outcome and may guide the development and
      selection of tumor-specific treatment approaches.

PMID- 26197072
TI  - Effective Feedback Procedures in Games for Health.
AB  - Feedback on game performance can be provided in many ways (e.g., cumulative
      points on game achievements, points on selected aspects of game play,
      biofeedback, brief statements offered during gameplay on choices made, verbal
      feedback at end of gameplay on overall performance, etc.). Feedback could be used
      motivationally to maintain player interest and involvement, informationally to
      guide the player in more effective choices, to build player confidence, and for a
      variety of other purposes. Although diverse feedback types and purposes are
      possible, some are more likely to be useful and effective. We have contacted
      several accomplished game designers and game researchers to obtain their insights
      into issues in feedback in Games for Health Journal. 

PMID- 26197073
TI  - Architecture and Imagery: A Profile of Serious Game Developer Archimage, Inc.

PMID- 26197074
TI  - Feasibility of an Active Game Program in a Dutch Pre-Vocational High School
      Setting.
AB  - OBJECTIVE: This study examined the use of an active gaming program in a pre
      vocational school over a 1-year period. SUBJECTS AND METHODS: Three hundred
      students (mean age, 13.3 years; range, 12-18 years) were invited to participate
      and exposed to the active game program called E-sportszone, in which they could
      participate during the school day and after school. Attendance to E-sportszone
      was assessed by objectively monitoring over a 1-year period and self-report.
      Questionnaires about E-sportszone attendance, physical activity (PA), and
      sedentary behavior and underlying psychosocial determinants were administered at
      baseline and after 1 year. RESULTS: Forty-two percent of the students attended
      the E-sportszone at least once. Attendance over the year varied from 1 day
      through 114 days (median, 3 days) with a peak during the E-sportszone marathon
      that was organized. Multivariate analysis showed boys used the E-sportszone more
      than girls (odds ratio [OR] 2.8) and older students were less likely to be users
      than younger students (OR 0.4). Furthermore, students who had a more positive
      attitude toward PA (OR 1.5) or who had higher scores on intention to use the E
      sportszone (OR 1.5) were more likely to engage in active gaming than those who
      had lower scores. CONCLUSIONS: A substantial group of at-risk students (i.e.,
      high body mass index, low PA, and high level of sedentary behavior) used the E
      sportszone at least once. However, frequency of usage was low, resulting in
      limited contribution to PA behavior. Long-term use was challenging, and future
      studies should focus on strategies to encourage continued use of active games in
      this type of pre-vocational school setting.

PMID- 26197075
TI  - The Efficacy of Casual Videogame Play in Reducing Clinical Depression: A
      Randomized Controlled Study.
AB  - BACKGROUND: Depression is a debilitating illness that is estimated to affect more
      than 300 million people worldwide. Although there has been some success in
      treatment of this illness with pharmaceuticals and behavioral techniques like
      cognitive behavioral therapy, these are often costly and have stigma associated
      with them. The purpose of this study was to test whether a prescribed regimen of
      casual videogame (CVG) play could reduce symptoms associated with depression.
      SUBJECTS AND METHODS: Participants were screened for depression using the Patient
      Health Questionnaire-9 (PHQ-9). They were then randomized into the control (n=29)
      or experimental (n=30) group. Experimental participants were prescribed to play
      CVGs three times per week (with 24 hours between each session), for 30 minutes,
      over a 1-month period. Control participants surfed the National Institute of
      Mental Health's Web page on depression. The instrument used to test the
      hypothesis was the PHQ-9. RESULTS: Repeated-measures statistical analyses
      revealed there was a significant interaction of group and time, supporting the
      hypothesis that the groups would be different after the intervention. Moreover,
      when data were compared using tests of within-subjects contrasts between baseline
      (Time 1) and the end of the 1-month study (Time 3), we found significant
      decreases in depression symptoms in the experimental group. When this was
      compared with the control group changes, the results were still significant.
      CONCLUSIONS: We found that a prescribed regimen of playing CVGs significantly
      reduced symptoms of clinical depression as measured by the PHQ-9. Clinicians
      should consider these low-cost CVGs as a possible intervention to address
      psychological and somatic symptoms associated with depression.

PMID- 26197076
TI  - Real Life Active Gaming Practices of 7-11-Year-Old Children.
AB  - OBJECTIVE: In the laboratory, active gaming has been shown to increase physical
      activity levels in children compared with seated media activities. The
      information is sparse, however, about children's real life active gaming
      practices, and the laboratory protocols used thus far might not be
      representative. The purpose of the present study was to establish the
      sociodemographic characteristics, real life active gaming practices, and reasons
      for gameplay, to later inform intervention studies. MATERIALS AND METHODS: An
      "Active Gaming Questionnaire" was purposely developed and distributed to 44 7-11
      year-old children and their parents. Forty questionnaires were completed and
      returned. RESULTS: Analysis found 95 percent of the children had access to active
      gaming consoles "at home." The favorite console was the Nintendo (Kyoto, Japan)
      WiiTM, and the favorite game was Nintendo "Wii Sports." The majority of children
      frequently played active games against other people. The average reported
      gameplay time was 81 minutes on 1-2 days per week, usually on a Saturday. More
      than half of the children (52.5 percent) consumed foods and/or drinks during
      play, which was significantly associated (P=0.000) with an extended average
      gameplay time (increased by 25 minutes). The majority of participants (65
      percent) considered active gaming to be an alternative form of exercise, and main
      reasons for active videogame play included for entertainment, health benefits,
      and the environment. CONCLUSIONS: In conclusion, children 9.3+/-1.4 years old
      typically play Nintendo "Wii Sports," once or twice per week for 81 minutes.
      Reported active gameplay time is extended by 25 minutes when food and/or drinks
      are consumed.

PMID- 26197077
TI  - "Alien Health Game": An Embodied Exergame to Instruct in Nutrition and MyPlate.
AB  - OBJECTIVE: A feasibility study was run on an immersive, embodied exergame ("Alien
      Health Game") designed to teach 4th-12th-grade students about nutrition and
      several U.S. Department of Agriculture MyPlate guidelines. This study assessed
      acceptability and limited efficacy. Students learned about the amount of
      nutrients and optimizers in common food items and practiced making rapid food
      choices while engaging in short cardiovascular activities. SUBJECTS AND METHODS:
      Nineteen 4th graders played a "mixed reality" game that included both digital
      components (projected graphics on the floor) and tangible, physical components
      (hand-held motion-tracking wands). Players made food choices and experienced
      immediate feedback on how each item affected the Alien avatar's alertness/health
      state. One member of the playing dyad had to run short distances to make the game
      work. The final level included a digital projection of the MyPlate icon, and each
      food item filled the appropriate quadrant dynamically. RESULTS: All students
      remained engaged with the game after approximately 1 hour of play. Significant
      learning gains were seen on a pretest and posttest that assessed nutrition
      knowledge (paired t18=4.13, P<0.001). In addition, significant learning gains
      were also seen in knowledge regarding MyPlate (paired t18=3.29, P<0.004).
      CONCLUSIONS: Results suggest preliminary feasibility via demonstrated
      acceptability and improved within-group content knowledge. Future research should
      explore improved measures of knowledge gains, alternative mechanisms for
      supporting the game mechanics to increase the scalability of the system (i.e.,
      via Kinect((r)) [Microsoft((r)), Redmond, WA] sensors), and the formal evaluation
      of the system via a randomized controlled trial.

PMID- 26197078
TI  - Active Screen Time Among U.S. Youth Aged 9-18 Years, 2009.
AB  - OBJECTIVE: This study documented the prevalence of active screen time (i.e.,
      screen time that includes active games, exercise or dance videos, or TV exercise
      programs) and identified characteristics associated with it among youth 9-18
      years of age. SUBJECTS AND METHODS: This cross-sectional study was conducted on a
      convenience sample of 1,165 youth using the 2009 Styles Surveys; data were
      weighted to approximate the Current Population Survey. We calculated descriptive
      statistics and conducted multivariable logistic regression to identify
      characteristics associated with active screen time by estimating adjusted odds
      ratio (aOR) and 95 percent confidence intervals (CIs). RESULTS: The sample
      comprised 51.4 percent boys, and almost 60 percent were non-Hispanic white. The
      prevalence of active screen time >=1 hour/day was 31.2 percent on a typical
      school day and 41.6 percent on a typical weekend day. Logistic regression
      revealed youth with physical activity of 3-5 days/week had higher odds of active
      screen time >=1 hour/day compared with youth with no physical activity (aOR
      school day=2.8, 95 percent CI 1.5-5.2; aOR weekend day=2.3, 95 percent CI 1.4
      3.9). Certain characteristics (i.e., sex, age group, race/ethnicity, income, and
      sedentary screen time) were significantly associated with active screen time >=1
      hour/day, but associations were inconsistent for school and weekend days.
      CONCLUSIONS: Three in 10 youth are engaging in at least 1 hour of active screen
      time on school days, and about 4 in 10 youth are engaging in at least one hour on
      weekend days. Understanding the use of active screen time and associated
      characteristics are important for developing interventions addressing screen time
      and physical activity.

PMID- 26197079
TI  - Morphological Profiles of RNAi-Induced Gene Knockdown Are Highly Reproducible but
      Dominated by Seed Effects.
AB  - RNA interference and morphological profiling-the measurement of thousands of
      phenotypes from individual cells by microscopy and image analysis-are a
      potentially powerful combination. We show that morphological profiles of RNAi
      induced knockdown using the Cell Painting assay are in fact highly sensitive and
      reproducible. However, we find that the magnitude and prevalence of off-target
      effects via the RNAi seed-based mechanism make morphological profiles of RNAi
      reagents targeting the same gene look no more similar than reagents targeting
      different genes. Pairs of RNAi reagents that share the same seed sequence produce
      image-based profiles that are much more similar to each other than profiles from
      pairs designed to target the same gene, a phenomenon previously observed in small
      scale gene-expression profiling experiments. Various strategies have been used to
      enrich on-target versus off-target effects in the context of RNAi screening where
      a narrow set of phenotypes are measured, mostly based on comparing multiple
      sequences targeting the same gene; however, new approaches will be needed to make
      RNAi morphological profiling (that is, comparing multi-dimensional phenotypes)
      viable. We have shared our raw data and computational pipelines to facilitate
      research. 

PMID- 26197080
TI  - Parameters of the assessment of voice quality and clinical manifestation of
      rheumatoid arthritis.
AB  - PURPOSE: The aim of the study was to investigate the voice quality parameters in
      72 rheumatoid arthritis (RA) patients and their relationships with the clinical
      manifestations and disease activity. The control group consisted of 30 healthy
      subjects. MATERIAL AND METHODS: All RA patients were evaluated by extensive
      clinical, laboratory and radiographic studies. The phoniatric assessment included
      the analysis of vocal folds vibrations by digital stroboscopy (DS) of the larynx
      using HRES ENDOCAM 5562 system, digital kymography (DKG) and High-Speed Digital
      Imaging (HSDI) technique. The acoustic voice analysis was conducted using
      DiagnoScope Specialist program. RESULTS: Voice quality disorders were registered
      in 32 (44.44%) RA patients and observed more frequently in patients with moderate
      and severe activity (DAS28>=3.2) than in mild RA. In digital stroboscopy,
      confirmed by digital kymography, the hypofunctional dysphonia was observed
      especially in patients with DAS28>=3.2. Outcomes of the subjective assessment of
      voice quality were in accordance with the objective parameters and acoustic voice
      examination. CONCLUSIONS: In RA patients the most frequent voice quality
      disorders with hypofunctional dysphonia were registered. The relationships
      between voice quality disorders, clinical activity and radiographic progression
      of RA patients were observed. Digital stroboscopy, digital kymography, High-Speed
      Digital Imaging and acoustic voice analysis used in the complex diagnosis of RA
      confirmed the presence of pathological changes in the larynx. There is a need of
      cooperation between rheumatologists and phoniatricians in the diagnosis and
      treatment of dysphonia in RA patients.

PMID- 26197081
TI  - Experimental and chemoinformatics evaluation of some physicochemical properties
      of excipients influencing release kinetics of the acidic drug ibuprofen.
AB  - In the present study, ibuprofen, a nonsteroidal anti-inflammatory drug was used
      in the formulation of tablets using three polymers representing different
      categories (immediate, moderate and extended release). Prepared tablets were
      evaluated for different post-compression parameters including dissolution and
      transportability studies. In vitro dissolution studies indicated Korsmeyer-Peppas
      as a best fit model, however, the transport of the drug was found to be
      influenced by its rate of release. A total of 118 molecular descriptors
      representing physicochemical and topological properties of polymeric structure
      was calculated and correlated with formulation characteristics for model
      generation. Further, predictive quantitative-structure property relationship
      models were developed for correlating polymeric descriptors with formulation
      properties containing acidic drug (ibuprofen). Developed models exhibited good
      predictability for formulation characteristics as indicated by squared
      correlation coefficients (>0.9). Such models could have an ability to predict the
      formulation properties as well as composition for desired characteristics with
      saving of time, material and cost. 

PMID- 26197082
TI  - The Outwardly Rectifying Current of Layer 5 Neocortical Neurons that was
      Originally Identified as "Non-Specific Cationic" Is Essentially a Potassium
      Current.
AB  - In whole-cell patch clamp recordings from layer 5 neocortical neurons, blockade
      of voltage gated sodium and calcium channels leaves a cesium current that is
      outward rectifying. This current was originally identified as a "non-specific
      cationic current", and subsequently it was hypothesized that it is mediated by
      TRP channels. In order to test this hypothesis, we used fluorescence imaging of
      intracellular sodium and calcium indicators, and found no evidence to suggest
      that it is associated with influx of either of these ions to the cell body or
      dendrites. Moreover, the current is still prominent in neurons from TRPC1-/- and
      TRPC5-/- mice. The effects on the current of various blocking agents, and
      especially its sensitivity to intracellular tetraethylammonium, suggest that it
      is not a non-specific cationic current, but rather that it is generated by cesium
      permeable delayed rectifier potassium channels. 

PMID- 26197083
TI  - MMP, VEGF and TIMP as prognostic factors in recurring bladder cancer.
AB  - OBJECTIVES: To investigate the clinical correlates and prognostic utility of MMP,
      VEGF and TIMP genes expression in bladder cancer (BCa) recurrence. METHODS:
      Expression of MMP1, MMP2, MMP9, VEGFA and TIMP1, TIMP3 was analyzed by qRT-PCR
      using SYBR Green in peripheral blood leukocytes (PBLs) of BCa patients at two
      time points (diagnosis (n=40), and first recurrence (n=40)) and an age-matched
      group of healthy controls (n=100). Plasma concentrations of MMP1 (pro- and active
      forms) were measured using ELISA in BCa patients. RESULTS: The expression of MMP1
      mRNA was significantly lower in BCa patients with first recurrence compared to
      control (p=0.019). Expression of other genes did not differ significantly between
      the groups. MMP9 gene expression was associated with differentiation grade
      (p=0.043), with the highest expression in poorly differentiated tumors (G3) and
      was higher in smokers than in non-smokers (p=0.039) in BCa patients at diagnosis.
      The results at two time points showed that MMP9 and VEGFA genes expression was
      increased in patients with moderately differentiated BCa (p=0.029), and advanced
      pathologic stage (p=0.048), respectively. Moreover, gene expression of TIMP1 was
      increased for G3 (p=0.043), and was decreased for early recurrence (p=0.003).
      CONCLUSIONS: Our study suggests that the expression of MMP9 in PBLs of BCa
      patients at diagnosis is associated with the differentiation grade of the BCa,
      and smoking status. Genes expression of MMP9, VEGFA and TIMP1 in PBLs may play a
      pivotal role in regulation of progression of BCa. Additionally, TIMP1 gene
      expression may be important factor for early recurrence of BCa.

PMID- 26197084
TI  - Investigation of Timing to Switch Control Mode in Powered Knee Prostheses during
      Task Transitions.
AB  - Current powered prosthetic legs require switching control modes according to the
      task the user is performing (e.g. level-ground walking, stair climbing, walking
      on slopes, etc.). To allow prosthesis users safely and seamlessly transition
      between tasks, it is critical to determine when to switch the prosthesis control
      mode during task transitions. Our previous study defined critical timings for
      different types of task transitions in ambulation; however, it is unknown whether
      it is the unique timing that allows safe and seamless transitions. The goals of
      this study were to (1) systematically investigate the effects of mode switch
      timing on the prosthesis user's performance in task transitions, and (2) identify
      appropriate timing to switch the prosthesis control mode so that the users can
      seamlessly transition between different locomotion tasks. Five able-bodied (AB)
      and two transfemoral (TF) amputee subjects were tested as they wore a powered
      knee prosthesis. The prosthesis control mode was switched manually at various
      times while the subjects performed different types of task transitions. The
      subjects' task transition performances were evaluated by their walking balance
      and success in performing seamless task transitions. The results demonstrated
      that there existed a time window within which switching the prosthesis control
      mode neither interrupted the subjects' task transitions nor disturbed their
      walking balance. Therefore, the results suggested the control mode switching of a
      lower limb prosthesis can be triggered within an appropriate time window instead
      of a specific timing or an individual phase. In addition, a generalized criterion
      to determine the appropriate mode switch timing was proposed. The outcomes of
      this study could provide important guidance for future designs of neurally
      controlled powered knee prostheses that are safe and reliable to use.

PMID- 26197086
TI  - Damage-associated molecular patterns and their pathological relevance in diabetes
      mellitus.
AB  - Diabetes, a group of metabolic and age-related diseases, is a major global health
      problem, the incidence of which has increased dramatically in recent decades.
      Type 1 diabetes mellitus (T1DM) is a complex, T cell-mediated autoimmune disease
      characterized by immune cell infiltration and chronic inflammation in the islets
      of Langerhans. Type 2 diabetes mellitus (T2DM) is a complex metabolic disease
      characterized by hyperglycemia (high blood sugar) resulting from insulin
      resistance and beta-cell dysfunction. The involvement of inflammatory processes,
      such as immune cell infiltration, and chronic inflammation in the pathogenesis of
      diabetes is less well understood in T2DM than in T1DM. However, studies conducted
      in the past decade have shown a strong link between inflammation and metabolic
      dysfunction. They have also shown that chronic inflammation plays a key role in
      the pathogenesis of both T1DM and T2DM. Two immunological factors commonly
      contribute to the pathogenesis of diabetes: the activation of inflammasomes and
      the release of proinflammatory cytokines in response to damage-associated
      molecular patterns (DAMPs). Inflammasomes are intracellular multiprotein
      molecular platforms. DAMPs act as endogenous danger signals. Here, we review
      current research on the function(s) of inflammasomes and DAMPs and discuss their
      pathological relevance and therapeutic implications in diabetes. 

PMID- 26197085
TI  - Evaluation of Live Recombinant Nonpathogenic Leishmania tarentolae Expressing
      Cysteine Proteinase and A2 Genes as a Candidate Vaccine against Experimental
      Canine Visceral Leishmaniasis.
AB  - Canine Visceral Leishmaniasis (CVL) is a major veterinary and public health
      problem caused by Leishmania infantum (L. infantum) in many endemic countries. It
      is a severe chronic disease with generalized parasite spread to the
      reticuloendothelial system, such as spleen, liver and bone marrow and is often
      fatal when left untreated. Control of VL in dogs would dramatically decrease
      infection pressure of L. infantum for humans, since dogs are the main domestic
      reservoir. In the past decade, various subunits and DNA antigens have been
      identified as potential vaccine candidates in experimental animal models, but
      none has been approved for human use so far. In this study, we vaccinated
      outbreed dogs with a prime-boost regimen based on recombinant L. tarentolae
      expressing the L. donovani A2 antigen along with cysteine proteinase genes (CPA
      and CPB without its unusual C-terminal extension (CPB-CTE) and evaluated its
      immunogenicity and protective immunity against L. infantum infectious challenge.
      We showed that vaccinated animals produced significantly higher levels of IgG2,
      but not IgG1, and also IFN-gamma and TNF-alpha, but low IL-10 levels, before and
      after challenge as compared to control animals. Protection in dogs was also
      correlated with a strong DTH response and low parasite burden in the vaccinated
      group. Altogether, immunization with recombinant L. tarentolae A2-CPA-CPB-CTE was
      proven to be immunogenic and induced partial protection in dogs, hence
      representing a promising live vaccine candidate against CVL. 

PMID- 26197087
TI  - Community-Based Outbreak of Neisseria meningitidis Serogroup C Infection in Men
      who Have Sex with Men, New York City, New York, USA, 2010-2013.
AB  - In September 2012, the New York City Department of Health and Mental Hygiene
      identified an outbreak of Neisseria meningitidis serogroup C invasive
      meningococcal disease among men who have sex with men (MSM). Twenty-two case
      patients and 7 deaths were identified during August 2010-February 2013. During
      this period, 7 cases in non-MSM were diagnosed. The slow-moving outbreak was
      linked to the use of websites and mobile phone applications that connect men with
      male sexual partners, which complicated the epidemiologic investigation and
      prevention efforts. We describe the outbreak and steps taken to interrupt
      transmission, including an innovative and wide-ranging outreach campaign that
      involved direct, internet-based, and media-based communications; free vaccination
      events; and engagement of community and government partners. We conclude by
      discussing the challenges of managing an outbreak affecting a discrete community
      of MSM and the benefits of using social networking technology to reach this at
      risk population. 

PMID- 26197088
TI  - Fucoidan Prevents the Progression of Osteoarthritis in Rats.
AB  - This study investigated the effects of fucoidan (extract from Hizikia fusiforme)
      on symptoms and inflammatory cytokine activation in rats with monosodium
      iodoacetate (MIA)-induced osteoarthritis (OA). Forty male SD rats were divided
      into five groups, including normal, negative control (MIA), positive control
      (Lyprinol), and two experimental groups treated with 50 or 100 mg/kg fucoidan.
      Weight-bearing assessments were done after MIA injection into the right knee to
      induce OA. After 14 days of treatment, microcomputed tomographic (micro-CT)
      images were made of rat knee joints, and then animals were sacrificed for joint
      histology and inflammatory cytokine level assessments. MIA injection successfully
      induced OA by causing 40% weight-bearing imbalance, severe bone loss and
      cartilage degeneration, and markedly increased cytokine levels. However, fucoidan
      groups showed over 45% of imbalance and no articular cartilage surface lesions or
      change in subchondral trabecular bones in Micro-CT images. Histological analysis
      revealed that cartilage morphology and cell counts were also normal in the 100
      mg/kg fucoidan group. In addition, the 100 mg/kg fucoidan groups exhibited lower
      serum tumor necrosis factor alpha (TNF-alpha) (30%), interleukin 1 beta (IL
      1beta) (48%), and matrix metalloproteinase-1 (MMP-1) (65%) compared to the MIA
      groups. These results suggest that administration of fucoidan prevents the
      progression of OA in a MIA-induced OA rat model.

PMID- 26197089
TI  - The automatic processing of visual information at different visual acuity levels:
      An ERP study.
AB  - This study investigated the subjective visual acuity by recording ERPs elicited
      by task-irrelevant visual changes. Optotypes stimuli were presented in the center
      of the visual field at three threshold levels (supra-threshold, threshold and sub
      threshold) while participants were listening to stories. The results showed that
      neither vMMN nor P3a component was elicited by optotypes stimuli on the sub
      threshold condition, whereas, vMMN was elicited under supra-threshold and
      threshold conditions, with no significant differences between those vMMN
      amplitudes of two conditions. The P3a amplitude was larger for supra-threshold
      condition than that for threshold condition. These data demonstrated that the
      emergence of vMMN could only reflect the automatic detection of orientation
      changes in the supra-threshold and threshold conditions compared to the sub
      threshold condition, whereas the P3a amplitude could reflect the difference in
      processing of supra-threshold and threshold stimuli. 

PMID- 26197090
TI  - iCD8alpha cells: living at the edge of the intestinal immune system.

PMID- 26197091
TI  - Assessment of planning performance in clinical samples: Reliability and validity
      of the Tower of London task (TOL-F).
AB  - OBJECTIVE: Executive deficits are frequent sequelae of neurological and
      psychiatric disorders, but their adequate neuropsychological assessment is still
      a matter of contention, given that executive tasks draw on a multitude of
      cognitive processes that are often not sufficiently specified. In line with this,
      results on psychometric properties of the Tower of London, a task measuring
      planning ability as a prototypical executive function, are equivocal and
      furthermore lacking completely for adult clinical populations. METHODS: We used a
      structurally balanced item set implemented in the Tower of London (Freiburg
      version, TOL-F) that accounts for major determinants of problem difficulty beyond
      the commonly used minimum number of moves to solution. Split-half reliability,
      internal consistency, and criterion-related concurrent validity of TOL-F accuracy
      were assessed in patients with stroke (N = 60), Parkinson syndrome (N = 51), and
      mild cognitive impairment (N = 29), and healthy adults (N = 155). RESULTS: Across
      samples, mean split-half and lower-bound indices of reliability of accuracy
      scores were adequate (r >= .7) or higher. Compared to a subset of healthy
      controls matched for age, sex, and education levels, deficits in planning
      accuracy emerged for all three clinical samples. CONCLUSIONS: Based on
      consistently adequate reliability and a good criterion-related validity of
      accuracy scores, the TOL-F demonstrates its utility for testing planning ability
      in clinical samples and healthy adults. Using item sets systematically accounting
      for several determinants of task difficulty can thus significantly enhance the
      contended reliability of executive tasks and provide an opportunity to resolve
      the underspecification of cognitive processes contributing to executive
      functioning in health and disease.

PMID- 26197092
TI  - Neural networks supporting switching, hypothesis testing, and rule application.
AB  - We identified dynamic changes in recruitment of neural connectivity networks
      across three phases of a flexible rule learning and set-shifting task similar to
      the Wisconsin Card Sort Task: switching, rule learning via hypothesis testing,
      and rule application. During fMRI scanning, subjects viewed pairs of stimuli that
      differed across four dimensions (letter, color, size, screen location), chose one
      stimulus, and received feedback. Subjects were informed that the correct choice
      was determined by a simple unidimensional rule, for example "choose the blue
      letter". Once each rule had been learned and correctly applied for 4-7 trials,
      subjects were cued via either negative feedback or visual cues to switch to
      learning a new rule. Task performance was divided into three phases: Switching
      (first trial after receiving the switch cue), hypothesis testing (subsequent
      trials through the last error trial), and rule application (correct responding
      after the rule was learned). We used both univariate analysis to characterize
      activity occurring within specific regions of the brain, and a multivariate
      method, constrained principal component analysis for fMRI (fMRI-CPCA), to
      investigate how distributed regions coordinate to subserve different processes.
      As hypothesized, switching was subserved by a limbic network including the
      ventral striatum, thalamus, and parahippocampal gyrus, in conjunction with
      cortical salience network regions including the anterior cingulate and
      frontoinsular cortex. Activity in the ventral striatum was associated with
      switching regardless of how switching was cued; visually cued shifts were
      associated with additional visual cortical activity. After switching, as subjects
      moved into the hypothesis testing phase, a broad fronto-parietal-striatal network
      (associated with the cognitive control, dorsal attention, and salience networks)
      increased in activity. This network was sensitive to rule learning speed, with
      greater extended activity for the slowest learning speed late in the time course
      of learning. As subjects shifted from hypothesis testing to rule application,
      activity in this network decreased and activity in the somatomotor and default
      mode networks increased. 

PMID- 26197093
TI  - Susceptibility of Carrion Crows to Experimental Infection with Lineage 1 and 2
      West Nile Viruses.
AB  - West Nile virus (WNV) outbreaks in North America have been characterized by
      substantial die-offs of American crows (Corvus brachyrhynchos). In contrast, a
      low incidence of bird deaths has been observed during WNV epidemic activity in
      Europe. To examine the susceptibility of the western European counterpart of
      American crows, we inoculated carrion crows (Corvus corone) with WNV strains
      isolated in Greece (Gr-10), Italy (FIN and Ita09), and Hungary (578/10) and with
      the highly virulent North American genotype strain (NY99). We also inoculated
      American crows with a selection of these strains to examine the strains'
      virulence in a highly susceptible bird species. Infection with all strains,
      except WNV FIN, resulted in high rates of death and high-level viremia in both
      bird species and virus dissemination to several organs. These results suggest
      that carrion crows are highly susceptible to WNV and may potentially be useful as
      part of dead bird surveillance for early warning of WNV activity in Europe. 

PMID- 26197094
TI  - Hepatic artery injury during left hepatic trisectionectomy for colorectal liver
      metastasis treated by portal vein arterialization.
AB  - Portal vein arterialization (PVA) has been applied as a salvage procedure in
      hepatopancreatobiliary surgeries, including transplantation and liver resection,
      with revascularization for malignancies. Here we describe the use PVA as a
      salvage procedure following accidental injury of the hepatic artery to the
      remnant liver occurred during left hepatic trisectionectomy for colorectal liver
      metastases (CRLM). A 60-year-old man with cancer of the sigmoid colon and
      initially unresectable CRLM received 11 cycles of hepatic arterial infusion
      chemotherapy with 5-fluorouracil (1500mg/week), after which CRLM was downstaged
      to resectable. One month after laparoscopic sigmoidectomy, a left
      trisectionectomy and wedge resection of segment 6 were performed. The posterior
      branch of the right hepatic artery, the only feeding artery to the remnant liver,
      was injured and totally dissected. Because microsurgical reconstruction of the
      artery was impossible, PVA was used; PVA is the sole known procedure available
      when hepatic artery reconstruction is impossible. The patient then suffered
      portal hypertension, and closure of arterio-portal anastomosis using an
      interventional technique with angiography was eventually performed on
      postoperative day 73. Therefore, it is considered that because PVA is associated
      with severe postoperative portal hypertension, closure of the arterio-portal
      shunt should be performed as soon as possible on diagnosing portal hypertension. 

PMID- 26197095
TI  - Duodeno-colic fistula as a rare presentation of lung cancer - surgical treatment
      of a stage IV oligometastatic lung disease.
AB  - INTRODUCTION: Rare adenosquamous carcinomas have no defined standard approach
      given their low incidence. They present with nonspecific imaging characteristics
      and are described as having worse prognosis than other lung malignancies, with
      greater likelihood of local invasion and early metastasis. PRESENTATION OF CASE:
      Male caucasian patient, 43 years, 26 pack-year smoking history, presented with
      watery diarrhea, early emesis and loss of 25% body weight (20kg) in four weeks.
      Colonoscopy identified a left colonic mass. Abdominal CT/ultrasound showed a
      large fistulous lesion between the 4th portion of the duodenum and left colon. CT
      showed a solid mass in the right upper lung lobe. Endoscopy and transthoracic
      biopsy were inconclusive. En bloc D3 and D4 duodenectomy, proximal enterectomy
      and left hemicolectomy were performed, with inconclusive histology of the
      specimen. Three months later, a right upper lung lobectomy with lymphadenectomy
      was performed, revealing an adenosquamous carcinoma of lung origin, R0, staged as
      pT2pN0pM1b. Six months later, a single dural metastasis in the left
      cerebellopontine angle was detected and resected, with subsequent holocranial
      radiotherapy and systemic adjuvant chemotherapy. Patient is currently with 18
      months follow-up, in good general health and with no evidence of recurrent
      disease. DISCUSSION: There are no specific guidelines to treat oligometastatic
      adenosquamous lung carcinoma. Our approach was abdominal surgery as a life-saving
      procedure and, months later, oncological resection of primary lung tumor and
      metachronous metastasis to the brain. CONCLUSION: A systematic, patient-oriented,
      patient-shared, multidisciplinary approach is particularly relevant when dealing
      with atypical presentations of rare diseases in young patients.

PMID- 26197096
TI  - Silent pelvic splenosis: Case report.
AB  - INTRODUCTION: Splenosis is a benign, usually asymptomatic, condition involving
      autotransplantation of splenic tissue that occurs frequently after splenic
      rupture caused by trauma or surgery [1]. Up to 67% of the patients presenting
      splenic rupture may develop splenosis [2]. The interval of time between the
      initial trauma and the diagnosis varies from 3 to 45 years with an average
      interval of 21 years [3]. Since the finding of this entity is usually accidental,
      the real incidence is not well known. Although splenosis following traumatic
      splenectomy after traffic accidents is well-documented in the literature, there
      do not seem to be many reported cases where splenosis produced gynecological
      complications [4]. There were fewer than 100 cases of splenosis reported since
      the first report of Buchbinder and Lipkoff in 1939 [5] in the English language
      medical literature of which only a minority appeared in the gynecological
      literature. PRESENTATION OF CASE: A case of pelvic and omentum majus splenosis in
      a patient is presented. DISCUSSION: Pelvic splenosis remains a rare finding in
      clinical practice. In most reported cases in the literature, the diagnosis was
      not considered before surgery. This approach may obviate the need for invasive
      evaluation for a primary or secondary neoplasm, and thus unnecessary surgery, and
      therefore preserve probable functional splenic tissue. Our case was diagnosed
      using non-surgical modalities. CONCLUSION: Our case emphasizes the rare
      diagnosing of pelvic splenosis in the evaluating pelvic mass with the tissue
      evidence instead of surgery.

PMID- 26197098
TI  - Treatment guidelines for mental disorders: reality or illusion?

PMID- 26197097
TI  - Autophagy confers DNA damage repair pathways to protect the hematopoietic system
      from nuclear radiation injury.
AB  - Autophagy is essentially a metabolic process, but its in vivo role in nuclear
      radioprotection remains unexplored. We observed that ex vivo autophagy activation
      reversed the proliferation inhibition, apoptosis, and DNA damage in irradiated
      hematopoietic cells. In vivo autophagy activation improved bone marrow
      cellularity following nuclear radiation exposure. In contrast, defective
      autophagy in the hematopoietic conditional mouse model worsened the hematopoietic
      injury, reactive oxygen species (ROS) accumulation and DNA damage caused by
      nuclear radiation exposure. Strikingly, in vivo defective autophagy caused an
      absence or reduction in regulatory proteins critical to both homologous
      recombination (HR) and non-homologous end joining (NHEJ) DNA damage repair
      pathways, as well as a failure to induce these proteins in response to nuclear
      radiation. In contrast, in vivo autophagy activation increased most of these
      proteins in hematopoietic cells. DNA damage assays confirmed the role of in vivo
      autophagy in the resolution of double-stranded DNA breaks in total bone marrow
      cells as well as bone marrow stem and progenitor cells upon whole body
      irradiation. Hence, autophagy protects the hematopoietic system against nuclear
      radiation injury by conferring and intensifying the HR and NHEJ DNA damage repair
      pathways and by removing ROS and inhibiting apoptosis. 

PMID- 26197099
TI  - [Representations of mental illness in the Greek Press: 2001 vs 2011].
AB  - The media seem to have played a prominent role in shaping the contemporary social
      image of people with mental illness, by perpetuating the stigma attached to it.
      Worldwide, a vast amount of research findings converge to the stigmatizing
      representation of people with mental illness by the media, with reference to the
      dominant stereotype of violence. The present study aims to explore the
      representations of mental illness in the Greek Press using a quantitative and
      qualitative approach. Potential changes in the media portrayal of mental illness
      during the last decade are also being examined: findings are compared to those of
      a previous research that took place in 2001, following the same methodology. The
      sample consisted of press articles referring to mental illness, that were indexed
      daily from the Greek newspapers during the period July-November 2011. The items
      were categorized into thematic categories and further analyzed taking in account
      the use of stigmatizing vocabulary, the reproduction of common myths concerning
      mental illness, the overall valence of each article (stigmatizing, neutral or
      anti-stigmatizing) towards people with mental illness, as well as the contextual
      implications conveyed in the use of psychiatric terms as a metaphor. The largest
      thematic category that emerged from the sample was that referring to the
      repercussions of the economic crisis to mental health, followed by the category
      of articles where psychiatric terms are used as a metaphor. The comparisons made
      between 2001 and 2011 revealed an improved representation of mental illness in
      terms of stigma, especially regarding schizophrenia. The public expression of
      stigma has decreased, with fewer stigmatizing articles and notably more neutral
      in valence articles. The findings of this study suggest a decline of the media
      propensity for emotionally charged descriptions and a shift towards objective
      journalism regarding mental illness. This is most likely to be attributed to the
      anti-stigma campaigns, targeting media workers, that have been implemented during
      the last decade in Greece. Nevertheless, the public expression of stigma remains
      present by taking more subtle forms. Such examples are demonstrated by the
      semantic context of articles in which psychiatric terms are used as a metaphor,
      or by the recurrent reference of (unspecified) mental illness on the occasion of
      violent crime. 

PMID- 26197100
TI  - [Relationship of omicronccupational stress parameters with burn-out and perceived
      stress].
AB  - One of the major problems concerning mental healthcare professionals is burn-out
      as a set of symptoms associated with chronic stress that encompasses three
      dimensions: emotional exhaustion, depersonalization, and reduced personal
      accomplishment. Research has indicated that asylums are stressful environments
      where nurses are vulnerable to burn-out and occupational stress. There is a
      tendency for research studies to investigate causes of stress and ways of coping,
      but few studies, particularly in recent years, have considered burn-out and
      occupational stress among care staff at Greek asylum. Investigating possible
      correlation between occupational stress and burn-out is important for
      implementing appropriate interventional programmes, in order to reduce burn-out
      among healthcare staff while increasing employee productivity and morale. The aim
      of this study was the analysis of correlations between burn-out and occupational
      stress of care staff at Leros Psychiatric Hospital. Forty-nine employees were
      assessed by Maslach's Burn-out Inventory, the Scale of Job Content, the Perceived
      Stress Scale and sociodemographic questionnaire data. Higher wages are associated
      with older workers (x2=7.638, p=0.022), and years at work (x2=10.094, p=0.006).
      Men have more years of work on average at the asylum than women (t=3.605,
      p<0.001), and total working time (t=4.914, p<0.001). Emotional exhaustion is
      related positively to job demands (r=0.484, p<0.001) and psychophysiological
      stress (r=0.381, p=0.006) and negatively to support from colleagues (r=-0.332,
      p=0.019) and superiors (r=-0.296, p=0.038). A significant correlation was noted
      between lack of personal accomplish ment, depression (r=-0.283, p=0.048) and lack
      of job satisfaction (r=-0.430). We also found a significant negative correlation
      between depersonalization and support from superiors (r=-0.300, p=0.036). Also,
      employees who experienced high levels of perceived stress reported higher levels
      of depression (r=0.358, p=0.011), sleep problems (r=0.469, p<0.001),
      psychosomatic (r=0.381, p=0.006) and complex psychophysiological stress (r=0.525,
      p<0.001). A positive correlation has been revealed between job content and burn
      out in their three dimensions such us emotional exhaustion, depersonalization and
      personal accomplishment. Job content is positively associated with the three burn
      out dimensions making it necessary to address these issues through staff
      education in stress management. 

PMID- 26197101
TI  - [Neuropsychiatric manifestations in Parkinson's disease].
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease
      after Alzheimer's disease affecting 1-2% of the population over 60. Although
      diagnosed by its characteristic motor manifestations, PD may be preceded, and is
      frequently accompanied, by a wide range of psychiatric and cognitive symptoms.
      These symptoms are often more debilitating than its motor complications and it is
      nowadays appreciated that they can be an important cause of excess disability in
      PD, frequently necessitating hospitalization and institutionalization. Despite
      their frequent occurrence, most PD-related neuropsychiatric symptoms remain under
      recognized and undertreated in clinical practice and their diagnosis is
      challenging because of the overlap of the somatic features of the psychiatric
      disorders and the motor symptoms of PD. Even when identified, there is a common
      perception that many of these symptoms are untreatable. Their recognition is
      essential not only for ascertaining the functional status of patients but also
      for better appreciating the nature of the neurodegenerative process in PD. These
      symptoms may precede the onset of motor symptoms and can be used as screening
      tools allowing for very early disease identification and for trials of possible
      diseasemodifying interventions. The pathophysiology of neuropsychiatric symptoms
      in PD involves complex and multifactorial mechanisms, including disease-related
      and psychological factors. Alterations in neurotransmitters like dopamine,
      serotonin, acetylcholine, involving subcortical projections and synaptic and
      neuronal changes involving limbic and cortical structures combine to result in
      these nonmotor symptoms. Potentially earlier evaluation and treatment of comorbid
      psychiatric and cognitive disorders in PD could improve quality of life and
      patient productivity, reduce morbidity and caregiver burden, and minimize
      healthcare costs. Management strategies include adjustment of dopaminergic
      medication, use of psychotropic treatments and behavioral and psychological
      interventions. Dopaminergic medication may precipitate neuropsychiatric
      conditions, such as the dopamine dysregulation syndrome. The choice of
      psychotropic medication for the neuropsychiatric symptoms of PD is determined by
      a balance between potential benefit versus side effects, mostly in terms of
      worsening motor symptoms. Furthermore, treatments used in general psychiatry
      services may not be as effective in PD. This article provides an overview and
      focuses on the neuropsychiatric manifestations in PD including depression,
      anxiety, psychosis, apathy and fatigue, personality, sexual dysfunction, sleep
      disorders, cognitive impairment and dementia, impulse control disorders and
      related behaviours. The epidemiology, pathophysiology and risk factors, clinical
      presentation and management of the most common neuropsychiatric complications in
      PD are discussed. 

PMID- 26197102
TI  - [Prevention of alcohol dependence].
AB  - With the exception of cardiovascular diseases, no other medical condition causes
      more serious dysfunction or premature deaths than alcohol-related problems.
      Research results indicate that alcohol dependent individuals present an
      exceptionally poor level of quality of life. This is an outcome that highlights
      the necessity of planning and implementing preventive interventions on
      biological, psychological or social level, to be provided to individuals who make
      alcohol abuse, as well as to their families. Preventive interventions can be
      considered on three levels of prevention: (a) primary prevention, which is
      focused on the protection of healthy individuals from alcohol abuse and
      dependence, and may be provided on a universal, selective or indicated level, (b)
      secondary prevention, which aims at the prevention of deterioration regarding
      alcoholic dependence and relapse, in the cases of individuals already diagnosed
      with the condition and (c) tertiary prevention, which is focused at minimizing
      deterioration of functioning in chronically sufferers from alcoholic dependence.
      The term "quaternary prevention" can be used for the prevention of relapse. As
      for primary prevention, interventions focus on assessing the risk of falling into
      problematic use, enhancing protective factors and providing information and
      health education in general. These interventions can be delivered in schools or
      in places of work and recreation for young people. In this context, various
      programs have been applied in different countries, including Greece with positive
      results (Preventure, Alcolocks, LST, SFP, Alcohol Ignition Interlock Device).
      Secondary prevention includes counseling and structured help with the delivery of
      programs in schools and in high risk groups for alcohol dependence (SAP, LST).
      These programs aim at the development of alcohol refusal skills and behaviors,
      the adoption of models of behaviors resisting alcohol use, as well as
      reinforcement of general social skills. In the context of relevant interventions,
      various techniques are used, such as role playing. At the level of social policy,
      different measures may contribute to increase the effectiveness of preventive
      programs (e.g. prohibition of sale of alcohol in young people). Interventions of
      tertiary prevention aim at the development of motivation for abstinence in
      alcohol dependent individuals and the prevention of relapse, as well as the
      acquisition of new behaviors, which support modification of the problem of
      alcohol dependence. These interventions can take place in the context of
      psychotherapeutic follow-up provided to alcohol dependent individuals, and may
      include various short-term interventions, such as motivational interviewing, but
      also alternative forms of treatment (e.g. acupuncture, meditation). Elements of
      prevention in combination with elements of promotion of mental health may be
      incorporated in the same programme for alcohol dependence, endorsing similar or
      different activities, which may be complementary and may reinforce the
      effectiveness of the prevention program. Finally, it is necessary to raise the
      awareness of mental health professionals regarding prevention and provide
      specialized education to those who work in drug addiction programmes. Mental
      health professionals may act as therapists and as intervention coordinators, and
      performing these roles, they may contribute to the effectiveness of preventive
      programs and more generally to the treatment of disorders connected with alcohol
      use. 

PMID- 26197103
TI  - [Parent schools: definition, progress and structure].
AB  - The institution of parent training is not an innovation. It exists since the
      beginning of the previous century. Presently, the parent training programmes or
      the so-called parent schools in Greece are structured programmes with specific
      coverage and set goals, their ultimate purpose is the prevention of the mental
      health of the child and they belong to a variety of interventions for parents.
      They address to parents of infants, toddlers, children and adolescents and show
      several differences regarding the form, content, purpose and theoretical
      direction they are based on. There are three categories of parent training
      programs. The programs that address all parents of the general population, the
      programs that are designed and implemented in special groups of parents or for a
      special purpose and the programs that address parents and children with specific
      serious problems. Usually, depending on their orientation, the parent training
      programs have either a parent-child relationship orientation (humanistic) or a
      behavioral orientation (behavioral). Research in the field of parent training saw
      that interventions based on Cognitive Behavioral Theory seem to be more effective
      than other interventions. The parent training programs-schools of parents are
      applied in almost all the regions of Greece. Unfortunately the existing data
      related to the structure, the content, the theoretical background and the
      effectiveness of these programs is not enough. The present study tries to review
      the bibliography concerning the development of the parent training programmes.
      The most significant data about the categories of the training programmes, as
      well as information about the structure, the content and the cost of these
      programmes, are also reviewed. Finally, the most popular programmes are mentioned
      based on their impact, according to the results of the studies.

PMID- 26197104
TI  - Drivers of the US CO2 emissions 1997-2013.
AB  - Fossil fuel CO2 emissions in the United States decreased by ~11% between 2007 and
      2013, from 6,023 to 5,377 Mt. This decline has been widely attributed to a shift
      from the use of coal to natural gas in US electricity production. However, the
      factors driving the decline have not been quantitatively evaluated; the role of
      natural gas in the decline therefore remains speculative. Here we analyse the
      factors affecting US emissions from 1997 to 2013. Before 2007, rising emissions
      were primarily driven by economic growth. After 2007, decreasing emissions were
      largely a result of economic recession with changes in fuel mix (for example,
      substitution of natural gas for coal) playing a comparatively minor role. Energy
      climate policies may, therefore, be necessary to lock-in the recent emissions
      reductions and drive further decarbonization of the energy system as the US
      economy recovers and grows. 

PMID- 26197106
TI  - Low temperature synthesis of polyaniline-crystalline TiO2-halloysite composite
      nanotubes with enhanced visible light photocatalytic activity.
AB  - A series of one-dimensional polyaniline-crystalline TiO2-halloysite composite
      nanotubes with different mass ratio of polyaniline to TiO2 are facilely prepared
      by employing the low-temperature synthesis of crystalline TiO2 on halloysite
      nanotubes. The halloysite nanotubes can adsorb TiO2/polyaniline precursors and
      induce TiO2 nanocrystals/polyaniline to grow on the support in situ
      simultaneously. By simply adjusting the acidity of reaction system, PANI
      crystalline TiO2-HA composite nanotubes composed of anatase, a mixed phase TiO2
      and different PANI redox state are obtained. The XRD and UV-vis results show that
      the surface polyaniline sensitization has no effect on the crystalline structure
      of halloysite and TiO2 and the light response of TiO2 is extended to visible
      light regions. Photocatalysis test results reveal the photocatalytic activity
      will be affected by the pH value and the volume ratio of ANI to TTIP. The highest
      photocatalytic activity is achieved with the composite photocatalysts prepared at
      pH 0.5 and 1% volume ratio of ANI and TTIP owing to the sensitizing effect of
      polyaniline and the charge transfer from the photoexcited PANI sensitizer to
      TiO2. Moreover, the PANI-TiO2-HA composite nanotubes synthesized by one-step at
      pH 0.5 with 1% volume ratio of ANI to TTIP exhibit higher visible light
      photocatalytic activity than those synthesized by the two-step. Heterogeneous
      PANI-TiO2-HA composite nanotubes prepared at pH 0.5 exhibit a higher degradation
      activity than that prepared at pH 1.5. The redoped experiment proves that the
      PANI redox state plays the main contribution to the enhanced visible light
      catalytic degradation efficiency of PANI-TiO2-HA prepared at pH 0.5. Furthermore,
      the heterogeneous PANI-crystalline TiO2-HA nanotubes have good photocatalytic
      stability and can be reused four times with only gradual loss of activity under
      visible light irradiation. 

PMID- 26197105
TI  - A Highly Responsive Silicon Nanowire/Amplifier MOSFET Hybrid Biosensor.
AB  - This study demonstrates a hybrid biosensor comprised of a silicon nanowire (SiNW)
      integrated with an amplifier MOSFET to improve the current response of field
      effect-transistor (FET)-based biosensors. The hybrid biosensor is fabricated
      using conventional CMOS technology, which has the potential advantage of high
      density and low noise performance. The biosensor shows a current response of 5.74
      decades per pH for pH detection, which is 2.5 * 10(5) times larger than that of a
      single SiNW sensor. In addition, we demonstrate charged polymer detection using
      the biosensor, with a high current change of 4.5 * 10(5) with a 500 nM
      concentration of poly(allylamine hydrochloride). In addition, we demonstrate a
      wide dynamic range can be obtained by adjusting the liquid gate voltage. We
      expect that this biosensor will be advantageous and practical for biosensor
      applications which requires lower noise, high speed, and high density.

PMID- 26197107
TI  - RGD functionalized polymeric nanoparticles targeting periodontitis epithelial
      cells for the enhanced treatment of periodontitis in dogs.
AB  - Long term retention of antimicrobials with effective drug concentration in
      gingival crevicular fluid (GCF) is of vital importance for the treatment of
      chronic periodontitis. In this study, a novel epithelial cell-targeting
      nanoparticle drug delivery system by conjugating minocycline-loaded poly(ethylene
      glycol)-poly(lactic acid) (PEG-PLA) nanoparticles (NP-MIN) with RGD peptide were
      developed and administrated locally for targeting periodontitis epithelial cells
      and enhancing the treatment of periodontitis in dogs. Biodegradable NP-MIN was
      made with an emulsion/solvent evaporation technique. RGD peptide was conjugated
      to the surface of nanoparticles via Maleimide group reaction with hydrosulfide in
      RGD peptide (RGD-NP-MIN). Transmission electron microscopy examination and
      dynamic light scattering results revealed that RGD-NP-MIN had a sphere shape,
      with a mean diameter around 106nm. In vitro release of minocycline from RGD-NP
      MIN showed that RGD modification did not change the remarkable sustained
      releasing characteristic of NP-MIN. To elucidate the interaction of RGD-NP and
      epithelial cells, RGD-NP binding, uptake and cellular internalization mechanisms
      by calu-3 cells were investigated. It was shown RGD modification significantly
      enhanced nanoparticles binding and uptake by Calu-3 cells, and RGD-NP uptake was
      an energy-dependent process through receptor-mediated endocytosis. Both clathrin
      associated endocytosis and caveolae-dependent endocytosis pathway were involved
      in the RGD-NP uptake, and the intracellular transport of RGD-NP was related to
      lysosome and Golgi apparatus. Finally, in vivo pharmacokinetics of minocycline in
      the periodontal pockets and anti-periodontitis effects of RGD-NP-MIN on
      periodontitis-bearing dogs were evaluated. After local administration of RGD-NP
      MIN, minocycline concentration in gingival crevicular fluid decreased slowly and
      maintained an effective drug concentration for a longer time than that of NP-MIN.
      Anti-periodontitis effects demonstrated that RGD-NP-MIN could significantly
      decrease symptoms of periodontitis, which was better than any other control
      group. These findings suggested that these epithelial cell-targeting
      nanoparticles offered a novel and effective local delivery system for the
      treatment of periodontitis. 

PMID- 26197108
TI  - Molecular surface area based predictive models for the adsorption and diffusion
      of disperse dyes in polylactic acid matrix.
AB  - Two predictive models were presented for the adsorption affinities and diffusion
      coefficients of disperse dyes in polylactic acid matrix. Quantitative structure
      sorption behavior relationship would not only provide insights into sorption
      process, but also enable rational engineering for desired properties. The
      thermodynamic and kinetic parameters for three disperse dyes were measured. The
      predictive model for adsorption affinity was based on two linear relationships
      derived by interpreting the experimental measurements with molecular structural
      parameters and compensation effect: DeltaH degrees  vs. dye size and DeltaS
      degrees  vs. DeltaH degrees . Similarly, the predictive model for diffusion
      coefficient was based on two derived linear relationships: activation energy of
      diffusion vs. dye size and logarithm of pre-exponential factor vs. activation
      energy of diffusion. The only required parameters for both models are temperature
      and solvent accessible surface area of the dye molecule. These two predictive
      models were validated by testing the adsorption and diffusion properties of new
      disperse dyes. The models offer fairly good predictive ability. The linkage
      between structural parameter of disperse dyes and sorption behaviors might be
      generalized and extended to other similar polymer-penetrant systems. 

PMID- 26197110
TI  - Multiple Observers Can Share the Nonlocality of Half of an Entangled Pair by
      Using Optimal Weak Measurements.
AB  - We investigate the trade-off between information gain and disturbance for von
      Neumann measurements on spin-1/2 particles, and derive the measurement pointer
      state that saturates this trade-off, which turns out to be highly unusual. We
      apply this result to the question of whether the nonlocality of a single particle
      from an entangled pair can be shared among multiple observers that act
      sequentially and independently of each other, and show that an arbitrarily long
      sequence of such observers can all violate the Clauser-Horne-Shimony-Holt-Bell
      inequality. 

PMID- 26197111
TI  - Necessary and Sufficient Condition for Quantum State-Independent Contextuality.
AB  - We solve the problem of whether a set of quantum tests reveals state-independent
      contextuality and use this result to identify the simplest set of the minimal
      dimension. We also show that identifying state-independent contextuality graphs
      [R. Ramanathan and P. Horodecki, Phys. Rev. Lett. 112, 040404 (2014)] is not
      sufficient for revealing state-independent contextuality. 

PMID- 26197109
TI  - Therapeutical Administration of Peptide Pep19-2.5 and Ibuprofen Reduces
      Inflammation and Prevents Lethal Sepsis.
AB  - Sepsis is still a major cause of death and many efforts have been made to improve
      the physical condition of sepsis patients and to reduce the high mortality rate
      associated with this disease. While achievements were implemented in the
      intensive care treatment, all attempts within the field of novel therapeutics
      have failed. As a consequence new medications and improved patient stratification
      as well as a thoughtful management of the support therapies are urgently needed.
      In this study, we investigated the simultaneous administration of ibuprofen as a
      commonly used nonsteroidal anti-inflammatory drug (NSAID) and Pep19-2.5
      (Aspidasept), a newly developed antimicrobial peptide. Here, we show a
      synergistic therapeutic effect of combined Pep19-2.5-ibuprofen treatment in an
      endotoxemia mouse model of sepsis. In vivo protection correlates with a reduction
      in plasma levels of both tumor necrosis factor alpha and prostaglandin E, as a
      likely consequence of Pep19-2.5 and ibuprofen-dependent blockade of TLR4 and COX
      pro-inflammatory cascades, respectively. This finding is further characterised
      and confirmed in a transcriptome analysis of LPS-stimulated human monocytes. The
      transcriptome analyses showed that Pep19-2.5 and ibuprofen exerted a synergistic
      global effect both on the number of regulated genes as well as on associated gene
      ontology and pathway expression. Overall, ibuprofen potentiated the anti
      inflammatory activity of Pep19-2.5 both in vivo and in vitro, suggesting that
      NSAIDs could be useful to supplement future anti-sepsis therapies.

PMID- 26197112
TI  - Contextuality in Phase Space.
AB  - We present a general framework for contextuality tests in phase space using
      displacement operators. First, we derive a general condition that a single-mode
      displacement operator should fulfill in order to construct Peres-Mermin square
      and similar scenarios. This approach offers a straightforward scheme for
      experimental implementations of the tests via modular variable measurements. In
      addition to the continuous variable case, our condition can also be applied to
      finite-dimensional systems in discrete phase space, using Heisenberg-Weyl
      operators. This approach, therefore, offers a unified picture of contextuality
      with a geometric flavor. 

PMID- 26197113
TI  - How Statistical Forces Depend on the Thermodynamics and Kinetics of Driven Media.
AB  - We study the statistical force of a nonequilibrium environment on a quasistatic
      probe. In the linear regime, the isothermal work on the probe equals the excess
      work for the medium to relax to its new steady condition with a displaced probe.
      Also, the relative importance of reaction paths can be measured via statistical
      forces, and from second order onwards the force on the probe reveals information
      about nonequilibrium changes in the reactivity of the medium. We also show that
      statistical forces for nonequilibrium media are generally nonadditive, in
      contrast with the equilibrium situation. Both the presence of nonthermodynamic
      corrections to the forces and their nonadditivity put serious constraints on any
      formulation of nonequilibrium steady state thermodynamics. 

PMID- 26197114
TI  - Unscreening Modified Gravity in the Matter Power Spectrum.
AB  - Viable modifications of gravity that may produce cosmic acceleration need to be
      screened in high-density regions such as the Solar System, where general
      relativity is well tested. Screening mechanisms also prevent strong anomalies in
      the large-scale structure and limit the constraints that can be inferred on these
      gravity models from cosmology. We find that by suppressing the contribution of
      the screened high-density regions in the matter power spectrum, allowing a
      greater contribution of unscreened low densities, modified gravity models can be
      more readily discriminated from the concordance cosmology. Moreover, by variation
      of density thresholds, degeneracies with other effects may be dealt with more
      adequately. Specializing to chameleon gravity as a worked example for screening
      in modified gravity, employing N-body simulations of f(R) models and the halo
      model of chameleon theories, we demonstrate the effectiveness of this method. We
      find that a percent-level measurement of the clipped power at k<0.3h/Mpc can
      yield constraints on chameleon models that are more stringent than what is
      inferred from Solar System tests or distance indicators in unscreened dwarf
      galaxies. Finally, we verify that our method is also applicable to the Vainshtein
      mechanism. 

PMID- 26197115
TI  - First Direct Measurement of (12)C((12)C,n)(23)Mg at Stellar Energies.
AB  - Neutrons produced by the carbon fusion reaction (12)C((12)C,n)(23)Mg play an
      important role in stellar nucleosynthesis. However, past studies have shown large
      discrepancies between experimental data and theory, leading to an uncertain cross
      section extrapolation at astrophysical energies. We present the first direct
      measurement that extends deep into the astrophysical energy range along with a
      new and improved extrapolation technique based on experimental data from the
      mirror reaction (12)C((12)C,p)(23)Na. The new reaction rate has been determined
      with a well-defined uncertainty that exceeds the precision required by
      astrophysics models. Using our constrained rate, we find that
      (12)C((12)C,n)(23)Mg is crucial to the production of Na and Al in pop-III pair
      instability supernovae. It also plays a nonnegligible role in the production of
      weak s-process elements, as well as in the production of the important galactic
      gamma-ray emitter (60)Fe.

PMID- 26197116
TI  - Ultrahigh-Energy Debris from the Collisional Penrose Process.
AB  - Soon after the discovery of the Kerr metric, Penrose realized that superradiance
      can be exploited to extract energy from black holes. The original idea (involving
      the breakup of a single particle) yields only modest energy gains. A variant of
      the Penrose process consists of particle collisions in the ergoregion. The
      collisional Penrose process has been explored recently in the context of dark
      matter searches, with the conclusion that the ratio eta between the energy of
      postcollision particles detected at infinity and the energy of the colliding
      particles should be modest (eta?1.5). Schnittman [Phys. Rev. Lett. 113, 261102
      (2014)] has shown that these studies underestimated the maximum efficiency by
      about 1 order of magnitude (i.e., eta?15). In this work we show that particle
      collisions in the vicinity of rapidly rotating black holes can produce high
      energy ejecta and result in high efficiencies under much more generic conditions.
      The astrophysical likelihood of these events deserves further scrutiny, but our
      study hints at the tantalizing possibility that the collisional Penrose process
      may power gamma rays and ultrahigh-energy cosmic rays. 

PMID- 26197117
TI  - Equilibration Rates in a Strongly Coupled Nonconformal Quark-Gluon Plasma.
AB  - We initiate the study of equilibration rates of strongly coupled quark-gluon
      plasmas in the absence of conformal symmetry. We primarily consider a
      supersymmetric mass deformation within N=2^{*} gauge theory and use holography to
      compute quasinormal modes of a variety of scalar operators, as well as the energy
      momentum tensor. In each case, the lowest quasinormal frequency, which provides
      an approximate upper bound on the thermalization time, is proportional to
      temperature, up to a prefactor with only a mild temperature dependence. We find
      similar behavior in other holographic plasmas, where the model contains an
      additional scale beyond the temperature. Hence, our study suggests that the
      thermalization time is generically set by the temperature, irrespective of any
      other scales, in strongly coupled gauge theories. 

PMID- 26197118
TI  - Electron-Phonon Interactions, Metal-Insulator Transitions, and Holographic
      Massive Gravity.
AB  - Massive gravity is holographically dual to "realistic" materials with momentum
      relaxation. The dual graviton potential encodes the phonon dynamics, and it
      allows for a much broader diversity than considered so far. We construct a simple
      family of isotropic and homogeneous materials that exhibit an interaction-driven
      metal-insulator transition. The transition relates to the formation of polarons
      phonon-electron quasibound states that dominate the conductivities, shifting the
      spectral weight above a mass gap. We characterize the polaron gap, width, and
      dispersion. 

PMID- 26197119
TI  - Absence of Quantum Time Crystals.
AB  - In analogy with crystalline solids around us, Wilczek recently proposed the idea
      of "time crystals" as phases that spontaneously break the continuous time
      translation into a discrete subgroup. The proposal stimulated further studies and
      vigorous debates whether it can be realized in a physical system. However, a
      precise definition of the time crystal is needed to resolve the issue. Here we
      first present a definition of time crystals based on the time-dependent
      correlation functions of the order parameter. We then prove a no-go theorem that
      rules out the possibility of time crystals defined as such, in the ground state
      or in the canonical ensemble of a general Hamiltonian, which consists of not-too
      long-range interactions. 

PMID- 26197120
TI  - Casimir Energy of Confining Large N Gauge Theories.
AB  - Four-dimensional asymptotically free large N gauge theories compactified on
      S(R)(3)*R have a weakly coupled confining regime when R is small compared to the
      strong scale. We compute the vacuum energy of a variety of confining large N
      nonsupersymmetric gauge theories in this calculable regime, where the vacuum
      energy can be thought of as the S(3) Casimir energy. The N=infinity renormalized
      vacuum energy turns out to vanish in the class of theories we have examined. This
      matches an implication of a recently observed temperature-reflection symmetry of
      such systems.

PMID- 26197121
TI  - Axial Current Generation by P-Odd Domains in QCD Matter.
AB  - The dynamics of topological domains which break parity (P) and charge-parity (CP)
      symmetry of QCD are studied. We derive in a general setting that those local
      domains will generate an axial current and quantify the strength of the induced
      axial current. Our findings are verified in a top-down holographic model. The
      relation between the real time dynamics of those local domains and the chiral
      magnetic field is also elucidated. We finally argue that such an induced axial
      current would be phenomenologically important in a heavy-ion collisions
      experiment. 

PMID- 26197124
TI  - Results of a Direct Search Using Synchrotron Radiation for the Low-Energy (229)Th
      Nuclear Isomeric Transition.
AB  - We report the results of a direct search for the (229)Th (I(pi)=3/2(+)<-5/2(+))
      nuclear isomeric transition, performed by exposing (229)Th-doped LiSrAlF(6)
      crystals to tunable vacuum-ultraviolet synchrotron radiation and observing any
      resulting fluorescence. We also use existing nuclear physics data to establish a
      range of possible transition strengths for the isomeric transition. We find no
      evidence for the thorium nuclear transition between 7.3 eV and 8.8 eV with
      transition lifetime (1-2) s?tau?(2000-5600)  s. This measurement excludes roughly
      half of the favored transition search area and can be used to direct future
      searches.

PMID- 26197123
TI  - Low-Lying Structure of (50)Ar and the N=32 Subshell Closure.
AB  - The low-lying structure of the neutron-rich nucleus (50)Ar has been investigated
      at the Radioactive Isotope Beam Factory using in-beam gamma-ray spectroscopy with
      (9)Be((54)Ca,(50)Ar+gamma)X, (9)Be((55)Sc,(50)Ar+gamma)X, and
      (9)Be((56)Ti,(50)Ar+gamma)X multinucleon removal reactions at ~220  MeV/u. A
      gamma-ray peak at 1178(18) keV is reported and assigned as the transition from
      the first 2(+) state to the 0(+) ground state. A weaker, tentative line at
      1582(38) keV is suggested as the 4(1)(+)->2(1)(+) transition. The experimental
      results are compared to large-scale shell-model calculations performed in the
      sdpf model space using the SDPF-MU effective interaction with modifications based
      on recent experimental data for exotic calcium and potassium isotopes. The
      modified Hamiltonian provides a satisfactory description of the new experimental
      results for (50)Ar and, more generally, reproduces the energy systematics of low
      lying states in neutron-rich Ar isotopes rather well. The shell-model
      calculations indicate that the N=32 subshell gap in (50)Ar is similar in
      magnitude to those in (52)Ca and (54)Ti and, notably, predict an N=34 subshell
      closure in (52)Ar that is larger than the one recently reported in (54)Ca.

PMID- 26197125
TI  - PT-Symmetry-Breaking Chaos in Optomechanics.
AB  - We demonstrate PT-symmetry-breaking chaos in an optomechanical system, which
      features an ultralow driving threshold. In principle, this chaos will emerge once
      a driving laser is applied to the cavity mode and lasts for a period of time. The
      driving strength is inversely proportional to the starting time of chaos. This
      originally comes from the dynamical enhancement of nonlinearity by field
      localization in the PT-symmetry-breaking phase. Moreover, this chaos is
      switchable by tuning the system parameters so that a PT-symmetry phase transition
      occurs. This work may fundamentally broaden the regimes of cavity optomechanics
      and nonlinear optics. It offers the prospect of exploring ultralow-power-laser
      triggered chaos and its potential applications in secret communication. 

PMID- 26197126
TI  - Tunable Circularly Polarized Terahertz Radiation from Magnetized Gas Plasma.
AB  - It is shown, by simulation and theory, that circularly or elliptically polarized
      terahertz radiation can be generated when a static magnetic (B) field is imposed
      on a gas target along the propagation direction of a two-color laser driver. The
      radiation frequency is determined by ?[omega(p)(2)+omega(c)(2)/4]+omega(c)/2,
      where omega(p) is the plasma frequency and omega(c) is the electron cyclotron
      frequency. With the increase of the B field, the radiation changes from a single
      cycle broadband waveform to a continuous narrow-band emission. In high-B-field
      cases, the radiation strength is proportional to omega(p)(2)/omega(c). The B
      field provides a tunability in the radiation frequency, spectrum width, and field
      strength.

PMID- 26197127
TI  - Laser-Frequency Stabilization Based on Steady-State Spectral-Hole Burning in
      Eu(3+)?Y(2)SiO(5).
AB  - We present and analyze a method of laser-frequency stabilization via steady-state
      patterns of spectral holes in Eu(3+)?Y(2)SiO(5). Three regions of spectral holes
      are created, spaced in frequency by the ground-state hyperfine splittings of
      (151)Eu(3+). The absorption pattern is shown not to degrade after days of laser
      frequency stabilization. An optical frequency comparison of a laser locked to
      such a steady-state spectral-hole pattern with an independent cavity-stabilized
      laser and a Yb optical lattice clock demonstrates a spectral-hole fractional
      frequency instability of 1.0*10(-15)tau(-1/2) that averages to 8.5(
      1.8)(+4.8)*10(-17) at tau=73  s. Residual amplitude modulation at the frequency
      of the rf drive applied to the fiber-coupled electro-optic modulator is reduced
      to less than 1*10(-6) fractional amplitude modulation at tau>1  s by an active
      servo. The contribution of residual amplitude modulation to the laser-frequency
      instability is further reduced by digital division of the transmission and
      incident photodetector signals to less than 1*10(-16) at tau>1  s.

PMID- 26197128
TI  - Microwave Chip-Based Beam Splitter for Low-Energy Guided Electrons.
AB  - We present a novel beam splitter for low-energy electrons using a micro
      structured guiding potential created above the surface of a planar microwave
      chip. Beam splitting arises from smoothly transforming the transverse guiding
      potential for an electron beam from a single-well harmonic confinement into a
      double well, thereby generating two separated output beams with 5 mm lateral
      spacing. Efficient beam splitting is observed for electron kinetic energies up to
      3 eV, in excellent agreement with particle tracking simulations. We discuss
      prospects of this novel beam splitter approach for electron-based quantum matter
      wave optics experiments. 

PMID- 26197129
TI  - Bursts of Terahertz Radiation from Large-Scale Plasmas Irradiated by Relativistic
      Picosecond Laser Pulses.
AB  - Powerful terahertz (THz) radiation is observed from large-scale underdense
      preplasmas in front of a solid target irradiated obliquely with picosecond
      relativistic intense laser pulses. The radiation covers an extremely broad
      spectrum with about 70% of its energy located in the high frequency regime over
      10 THz. The pulse energy of the radiation is found to be above 100  MUJ per
      steradian in the laser specular direction at an optimal preplasma scale length
      around 40-50  MUm. Particle-in-cell simulations indicate that the radiation is
      mainly produced by linear mode conversion from electron plasma waves, which are
      excited successively via stimulated Raman scattering instability and self
      modulated laser wakefields during the laser propagation in the preplasma. This
      radiation can be used not only as a powerful source for applications, but also as
      a unique diagnostic of parametric instabilities of laser propagation in plasmas. 

PMID- 26197130
TI  - Cross-Scale Interactions between Electron and Ion Scale Turbulence in a Tokamak
      Plasma.
AB  - Multiscale gyrokinetic turbulence simulations with the real ion-to-electron mass
      ratio and beta value are realized for the first time, where the beta value is
      given by the ratio of plasma pressure to magnetic pressure and characterizes
      electromagnetic effects on microinstabilities. Numerical analysis at both the
      electron scale and the ion scale is used to reveal the mechanism of their cross
      scale interactions. Even with the real-mass scale separation, ion-scale
      turbulence eliminates electron-scale streamers and dominates heat transport, not
      only of ions but also of electrons. Suppression of electron-scale turbulence by
      ion-scale eddies, rather than by long-wavelength zonal flows, is also
      demonstrated by means of direct measurement of nonlinear mode-to-mode coupling.
      When the ion-scale modes are stabilized by finite-beta effects, the contribution
      of the electron-scale dynamics to the turbulent transport becomes non-negligible
      and turns out to enhance ion-scale turbulent transport. Damping of the ion-scale
      zonal flows by electron-scale turbulence is responsible for the enhancement of
      ion-scale transport. 

PMID- 26197131
TI  - Alpha Heating and Burning Plasmas in Inertial Confinement Fusion.
AB  - Estimating the level of alpha heating and determining the onset of the burning
      plasma regime is essential to finding the path towards thermonuclear ignition. In
      a burning plasma, the alpha heating exceeds the external input energy to the
      plasma. Using a simple model of the implosion, it is shown that a general
      relation can be derived, connecting the burning plasma regime to the yield
      enhancement due to alpha heating and to experimentally measurable parameters such
      as the Lawson ignition parameter. A general alpha-heating curve is found,
      independent of the target and suitable to assess the performance of all laser
      fusion experiments whether direct or indirect drive. The onset of the burning
      plasma regime inside the hot spot of current implosions on the National Ignition
      Facility requires a fusion yield of about 50 kJ. 

PMID- 26197132
TI  - Coherent Heteronuclear Spin Dynamics in an Ultracold Spinor Mixture.
AB  - We report the observation of coherent heteronuclear spin dynamics driven by
      interspecies spin-spin interaction in an ultracold spinor mixture, which
      manifests as periodical and well-correlated spin oscillations between two atomic
      species. In particular, we investigate the magnetic field dependence of the
      oscillations and find a resonance behavior which depends on both the linear and
      quadratic Zeeman effects and the spin-dependent interaction. We also demonstrate
      a unique knob for controlling the spin dynamics in the spinor mixture with
      species-dependent vector light shifts. 

PMID- 26197133
TI  - Connecting Berezinskii-Kosterlitz-Thouless and BEC Phase Transitions by Tuning
      Interactions in a Trapped Gas.
AB  - We study the critical point for the emergence of coherence in a harmonically
      trapped two-dimensional Bose gas with tunable interactions. Over a wide range of
      interaction strengths we find excellent agreement with the classical-field
      predictions for the critical point of the Berezinskii-Kosterlitz-Thouless (BKT)
      superfluid transition. This allows us to quantitatively show, without any free
      parameters, that the interaction-driven BKT transition smoothly converges onto
      the purely quantum-statistical Bose-Einstein condensation transition in the limit
      of vanishing interactions. 

PMID- 26197134
TI  - Imaging Molecular Motion: Femtosecond X-Ray Scattering of an Electrocyclic
      Chemical Reaction.
AB  - Structural rearrangements within single molecules occur on ultrafast time scales.
      Many aspects of molecular dynamics, such as the energy flow through excited
      states, have been studied using spectroscopic techniques, yet the goal to watch
      molecules evolve their geometrical structure in real time remains challenging. By
      mapping nuclear motions using femtosecond x-ray pulses, we have created real
      space representations of the evolving dynamics during a well-known chemical
      reaction and show a series of time-sorted structural snapshots produced by
      ultrafast time-resolved hard x-ray scattering. A computational analysis optimally
      matches the series of scattering patterns produced by the x rays to a multitude
      of potential reaction paths. In so doing, we have made a critical step toward the
      goal of viewing chemical reactions on femtosecond time scales, opening a new
      direction in studies of ultrafast chemical reactions in the gas phase. 

PMID- 26197135
TI  - Quantum Critical Scaling of Dirty Bosons in Two Dimensions.
AB  - We determine the dynamical critical exponent z appearing at the Bose glass to
      superfluid transition in two dimensions by performing large scale numerical
      studies of two microscopically different quantum models within the universality
      class: The hard-core boson model and the quantum rotor (soft core) model, both
      subject to strong on-site disorder. By performing many simulations at different
      system size L and inverse temperature beta close to the quantum critical point,
      the position of the critical point and the critical exponents, z, nu, and eta can
      be determined independently of any implicit assumptions of the numerical value of
      z, in contrast to most prior studies. This is done by a careful scaling analysis
      close to the critical point with a particular focus on the temperature dependence
      of the scaling functions. For the hard-core boson model we find z=1.88(8),
      nu=0.99(3), and eta=-0.16(8) with a critical field of h(c)=4.79(3), while for the
      quantum rotor model we find z=1.99(5), nu=1.00(2), and eta=-0.3(1) with a
      critical hopping parameter of t(c)=0.0760(5). In both cases do we find a
      correlation length exponent consistent with nu=1, saturating the bound nu>=2/d as
      well as a value of z significantly larger than previous studies, and for the
      quantum rotor model consistent with z=d.

PMID- 26197136
TI  - Gapped Surface States in a Strong-Topological-Insulator Material.
AB  - A three-dimensional strong-topological insulator or semimetal hosts topological
      surface states which are often said to be gapless so long as time-reversal
      symmetry is preserved. This narrative can be mistaken when surface state
      degeneracies occur away from time-reversal-invariant momenta. The mirror
      invariance of the system then becomes essential in protecting the existence of a
      surface Fermi surface. Here we show that such a case exists in the strong
      topological-semimetal Bi(4)Se(3). Angle-resolved photoemission spectroscopy and
      ab initio calculations reveal partial gapping of surface bands on the Bi(2)Se(3)
      termination of Bi(4)Se(3)(111), where an 85 meV gap along GammaK closes to zero
      toward the mirror-invariant GammaM azimuth. The gap opening is attributed to an
      interband spin-orbit interaction that mixes states of opposite spin helicity.

PMID- 26197137
TI  - Topological Valley Currents in Gapped Dirac Materials.
AB  - Gapped 2D Dirac materials, in which inversion symmetry is broken by a gap-opening
      perturbation, feature a unique valley transport regime. Topological valley
      currents in such materials are dominated by bulk currents produced by electronic
      states just beneath the gap rather than by edge modes. The system ground state
      hosts dissipationless persistent valley currents existing even when topologically
      protected edge modes are absent. Valley currents induced by an external bias are
      characterized by a quantized half-integer valley Hall conductivity. The undergap
      currents dominate magnetization and the charge Hall effect in a light-induced
      valley-polarized state. 

PMID- 26197138
TI  - Strain Doping: Reversible Single-Axis Control of a Complex Oxide Lattice via
      Helium Implantation.
AB  - We report on the use of helium ion implantation to independently control the out
      of-plane lattice constant in epitaxial La(0.7)Sr(0.3)MnO(3) thin films without
      changing the in-plane lattice constants. The process is reversible by a vacuum
      anneal. Resistance and magnetization measurements show that even a small increase
      in the out-of-plane lattice constant of less than 1% can shift the metal
      insulator transition and Curie temperatures by more than 100  degrees C. Unlike
      conventional epitaxy-based strain tuning methods which are constrained not only
      by the Poisson effect but by the limited set of available substrates, the present
      study shows that strain can be independently and continuously controlled along a
      single axis. This permits novel control over orbital populations through Jahn
      Teller effects, as shown by Monte Carlo simulations on a double-exchange model.
      The ability to reversibly control a single lattice parameter substantially
      broadens the phase space for experimental exploration of predictive models and
      leads to new possibilities for control over materials' functional properties.

PMID- 26197139
TI  - Spin-Fluctuation-Driven Nematic Charge-Density Wave in Cuprate Superconductors:
      Impact of Aslamazov-Larkin Vertex Corrections.
AB  - We present a microscopic derivation of the nematic charge-density wave (CDW)
      formation in cuprate superconductors based on the three-orbital d-p Hubbard model
      by introducing the vertex correction (VC) into the charge susceptibility. The CDW
      instability at q=(Delta(FS),0), (0,Delta(FS)) appears when the spin fluctuations
      are strong, due to the strong charge-spin interference represented by the VC.
      Here, Delta(FS) is the wave number between the neighboring hot spots. The
      obtained spin-fluctuation-driven CDW is expressed as the "intra-unit-cell orbital
      order" accompanied by the charge transfer between the neighboring atomic
      orbitals, which is actually observed by the scanning tunneling microscope
      measurements. We predict that the cuprate CDW and the nematic orbital order in Fe
      based superconductors are closely related spin-fluctuation-driven phenomena.

PMID- 26197140
TI  - Effective Field Theory of the Disordered Weyl Semimetal.
AB  - In disordered Weyl semimetals, mechanisms of topological origin lead to the
      protection against Anderson localization, and at the same time to different types
      of transverse electromagnetic response-the anomalous Hall and the chiral magnetic
      effect. We here apply field theory methods to discuss the manifestation of these
      phenomena at length scales that are beyond the scope of diagrammatic perturbation
      theory. Specifically, we show how an interplay of symmetry breaking and the
      chiral anomaly leads to a field theory containing two types of topological terms.
      Generating the unconventional response coefficients of the system, these terms
      remain largely unaffected by disorder, i.e., information on the chirality of the
      system remains visible even at large length scales. 

PMID- 26197141
TI  - Topological Surface States Originated Spin-Orbit Torques in Bi(2)Se(3).
AB  - The three dimensional topological insulator bismuth selenide (Bi(2)Se(3)) is
      expected to possess strong spin-orbit coupling and spin-textured topological
      surface states and, thus, exhibit a high charge to spin current conversion
      efficiency. We evaluate spin-orbit torques in Bi(2)Se(3)/Co(40)Fe(40)B(20)
      devices at different temperatures by spin torque ferromagnetic resonance
      measurements. As the temperature decreases, the spin-orbit torque ratio increases
      from ~0.047 at 300 K to ~0.42 below 50 K. Moreover, we observe a significant out
      of-plane torque at low temperatures. Detailed analysis indicates that the origin
      of the observed spin-orbit torques is topological surface states in Bi(2)Se(3).
      Our results suggest that topological insulators with strong spin-orbit coupling
      could be promising candidates as highly efficient spin current sources for
      exploring the next generation of spintronic applications.

PMID- 26197142
TI  - First-Order Melting of a Weak Spin-Orbit Mott Insulator into a Correlated Metal.
AB  - The electronic phase diagram of the weak spin-orbit Mott insulator (Sr(1
      x)La(x))(3)Ir(2)O(7) is determined via an exhaustive experimental study. Upon
      doping electrons via La substitution, an immediate collapse in resistivity occurs
      along with a narrow regime of nanoscale phase separation comprised of
      antiferromagnetic, insulating regions and paramagnetic, metallic puddles
      persisting until x~0.04. Continued electron doping results in an abrupt, first
      order phase boundary where the Neel state is suppressed and a homogenous,
      correlated, metallic state appears with an enhanced spin susceptibility and local
      moments. As the metallic state is stabilized, a weak structural distortion
      develops and suggests a competing instability with the parent spin-orbit Mott
      state.

PMID- 26197143
TI  - Braiding a Flock: Winding Statistics of Interacting Flying Spins.
AB  - When animal groups move coherently in the form of a flock, their trajectories are
      not all parallel, the individuals exchange their position in the group. In this
      Letter, we introduce a measure of this mixing dynamics, which we quantify as the
      winding of the braid formed from the particle trajectories. Building on a
      paradigmatic flocking model we numerically and theoretically explain the winding
      statistics and show that it is predominantly set by the global twist of the
      trajectories as a consequence of a spontaneous symmetry breaking. 

PMID- 26197144
TI  - Examining the Mechanical Equilibrium of Microscopic Stresses in Molecular
      Simulations.
AB  - The microscopic stress field provides a unique connection between atomistic
      simulations and mechanics at the nanoscale. However, its definition remains
      ambiguous. Rather than a mere theoretical preoccupation, we show that this fact
      acutely manifests itself in local stress calculations of defective graphene,
      lipid bilayers, and fibrous proteins. We find that popular definitions of the
      microscopic stress violate the continuum statements of mechanical equilibrium,
      and we propose an unambiguous and physically sound definition. 

PMID- 26197122
TI  - Observation of Charge Asymmetry Dependence of Pion Elliptic Flow and the Possible
      Chiral Magnetic Wave in Heavy-Ion Collisions.
AB  - We present measurements of pi(-) and pi(+) elliptic flow, v(2), at midrapidity in
      Au+Au collisions at ?[s(NN)]=200, 62.4, 39, 27, 19.6, 11.5, and 7.7 GeV, as a
      function of event-by-event charge asymmetry, A(ch), based on data from the STAR
      experiment at RHIC. We find that pi(-) (pi(+)) elliptic flow linearly increases
      (decreases) with charge asymmetry for most centrality bins at ?[s(NN)]=27  GeV
      and higher. At ?[s(NN)]=200  GeV, the slope of the difference of v(2) between pi(
      ) and pi(+) as a function of A(ch) exhibits a centrality dependence, which is
      qualitatively similar to calculations that incorporate a chiral magnetic wave
      effect. Similar centrality dependence is also observed at lower energies.

PMID- 26197145
TI  - Time-Frequency Analysis Reveals Pairwise Interactions in Insect Swarms.
AB  - The macroscopic emergent behavior of social animal groups is a classic example of
      dynamical self-organization, and is thought to arise from the local interactions
      between individuals. Determining these interactions from empirical data sets of
      real animal groups, however, is challenging. Using multicamera imaging and
      tracking, we studied the motion of individual flying midges in laboratory mating
      swarms. By performing a time-frequency analysis of the midge trajectories, we
      show that the midge behavior can be segmented into two distinct modes: one that
      is independent and composed of low-frequency maneuvers, and one that consists of
      higher-frequency nearly harmonic oscillations conducted in synchrony with another
      midge. We characterize these pairwise interactions, and make a hypothesis as to
      their biological function. 

PMID- 26197146
TI  - Hydrodynamic Trapping of Swimming Bacteria by Convex Walls.
AB  - Swimming bacteria display a remarkable tendency to move along flat surfaces for
      prolonged times. This behavior may have a biological importance but can also be
      exploited by using microfabricated structures to manipulate bacteria. The main
      physical mechanism behind the surface entrapment of swimming bacteria is,
      however, still an open question. By studying the swimming motion of Escherichia
      coli cells near microfabricated pillars of variable size, we show that cell
      entrapment is also present for convex walls of sufficiently low curvature.
      Entrapment is, however, markedly reduced below a characteristic radius. Using a
      simple hydrodynamic model, we predict that trapped cells swim at a finite angle
      with the wall and a precise relation exists between the swimming angle at a flat
      wall and the critical radius of curvature for entrapment. Both predictions are
      quantitatively verified by experimental data. Our results demonstrate that the
      main mechanism for wall entrapment is hydrodynamic in nature and show the
      possibility of inhibiting cell adhesion, and thus biofilm formation, using convex
      features of appropriate curvature. 

PMID- 26197148
TI  - Controlling the Location of Bare Nanoparticles in Polymer-Nanoparticle Blend
      Films by Adding Polymer-Grafted Nanoparticles.
AB  - We present molecular dynamics simulations of polymer-nanoparticle blends in films
      containing both grafted and ungrafted nanoparticles where the particle cores are
      identical and grafted chains are similar to a matrix polymer. Our results
      indicate that it is possible to control the location of bare nanoparticles in the
      film by adding small amounts of polymer-grafted nanoparticles. In the presence of
      a substrate, bare particles are entropically pushed to the surface. We observed
      that the introduction of grafted particles to the blend prevents the migration of
      bare particles to the surface. This unusual behavior is caused by the formation
      of binary aspherical clusters due to the presence of grafted particles. Hence,
      parameters including grafting density and the length of the grafted polymer play
      a significant role in dictating the spatial arrangement of bare particles in the
      blend film. At higher values of these parameters, the grafted particle core is
      shielded from depletion attractions causing the density of bare particles to
      increase back near the surface. 

PMID- 26197147
TI  - Generalized Manning Condensation Model Captures the RNA Ion Atmosphere.
AB  - RNA is highly sensitive to the ionic environment and typically requires Mg(2+) to
      form compact structures. There is a need for models capable of describing the ion
      atmosphere surrounding RNA with quantitative accuracy. We present a model of RNA
      electrostatics and apply it within coarse-grained molecular dynamics simulation.
      The model treats Mg(2+) ions explicitly to account for ion-ion correlations
      neglected by mean-field theories. Since mean-field theories capture KCl well, it
      is treated implicitly by a generalized Manning counterion condensation model. The
      model extends Manning condensation to deal with arbitrary RNA conformations,
      nonlimiting KCl concentrations, and the ion inaccessible volume of RNA. The model
      is tested against experimental measurements of the excess Mg(2+) associated with
      the RNA, Gamma(2+), because Gamma(2+) is directly related to the Mg(2+)-RNA
      interaction free energy. The excellent agreement with experiment demonstrates
      that the model captures the ionic dependence of the RNA free energy landscape.

PMID- 26197149
TI  - Probing Colloidal Gels at Multiple Length Scales: The Role of Hydrodynamics.
AB  - Colloidal gels are out-of-equilibrium structures, made up of a rarefied network
      of colloidal particles. Comparing experiments to numerical simulations, with
      hydrodynamic interactions switched off, we demonstrate the crucial role of the
      solvent for gelation. Hydrodynamic interactions suppress the formation of larger
      local equilibrium structures of closed geometry, and instead lead to the
      formation of highly anisotropic threads, which promote an open gel network. We
      confirm these results with simulations which include hydrodynamics. Based on
      three-point correlations, we propose a scale-resolved quantitative measure for
      the anisotropy of the gel structure. We find a strong discrepancy for
      interparticle distances just under twice the particle diameter between systems
      with and without hydrodynamics, quantifying the role of hydrodynamics from a
      structural point of view. 

PMID- 26197150
TI  - Direct Observation of the Dynamics of Self-Assembly of Individual Solvation
      Layers in Molecularly Confined Liquids.
AB  - Confined liquids organize in solidlike layers at the liquid-substrate interface.
      Here we use force-clamp spectroscopy AFM to capture the equilibrium dynamics
      between the broken and reformed states of an individual solvation layer in real
      time. Kinetic measurements demonstrate that the rupture of each individual
      solvation layer in structured liquids is driven by the rupture of a single
      interaction for 1-undecanol and by two interactions in the case of the ionic
      liquid ethylammonium nitrate. Our results provide a first description of the
      energy landscape governing the molecular motions that drive the packing and self
      assembly of each individual liquid layer. 

PMID- 26197151
TI  - What Can Interaction Webs Tell Us About Species Roles?
AB  - The group model is a useful tool to understand broad-scale patterns of
      interaction in a network, but it has previously been limited in use to food webs,
      which contain only predator-prey interactions. Natural populations interact with
      each other in a variety of ways and, although most published ecological networks
      only include information about a single interaction type (e.g., feeding,
      pollination), ecologists are beginning to consider networks which combine
      multiple interaction types. Here we extend the group model to signed directed
      networks such as ecological interaction webs. As a specific application of this
      method, we examine the effects of including or excluding specific interaction
      types on our understanding of species roles in ecological networks. We consider
      all three currently available interaction webs, two of which are extended plant
      mutualist networks with herbivores and parasitoids added, and one of which is an
      extended intertidal food web with interactions of all possible sign structures
      (+/+, -/0, etc.). Species in the extended food web grouped similarly with all
      interactions, only trophic links, and only nontrophic links. However, removing
      mutualism or herbivory had a much larger effect in the extended plant-pollinator
      webs. Species removal even affected groups that were not directly connected to
      those that were removed, as we found by excluding a small number of parasitoids.
      These results suggest that including additional species in the network provides
      far more information than additional interactions for this aspect of network
      structure. Our methods provide a useful framework for simplifying networks to
      their essential structure, allowing us to identify generalities in network
      structure and better understand the roles species play in their communities. 

PMID- 26197152
TI  - Needle Curette Technique for Hand Surgery.
AB  - Curettage of lesions in the hand often requires fine instruments of varying
      angles for a thorough debridement. This can be seen with debridement of
      enchondromas of the phalanges when minimizing the size of the cortical window is
      desired. In this technical note, the authors describe the modification of an 18-G
      needle so that it may be used as a small curette when standard small curettes are
      not available or optimal. 

PMID- 26197153
TI  - Treatment of Painful Nonunion of the Distal Phalanx in the Finger With Bone Graft
      and Dorsal Reverse Adipofascial Flap Based on an Exteriorized Pedicle.
AB  - Reconstruction of the distal phalanx bone in cases with painful nonunion is a
      rare and challenging problem. To restore anatomy and to provide a good cover for
      the bone graft, an intact nailbed is often required due to the proximity of these
      2 structures. We present 3 cases of distal phalanx reconstruction performed with
      a free corticocancellous bone graft from the distal radius and nailbed
      reconstruction with a homodigital dorsal reverse adipofascial flap based on an
      exteriorized pedicle that avoids the dissection of the germinal matrix of the
      nail. All bone grafts consolidated and all flaps survived. All nail plates grew
      back with no deformity. In this rare but challenging problem, our combined
      technique appears to be a valid option that enhances the possibility of good bone
      healing and maximizes the cosmetic result. 

PMID- 26197154
TI  - Case Study: Osteosynthesis, Tenodesis Effect, and Side-to-Side Tendon Repair in
      Hand Transplantation.
AB  - Osteosynthesis and tendon repair are essential in upper extremity transplantation
      to optimally restore function. Transplant surgeons should be aware of all
      technical issues involved in osteosynthesis, tendon balancing, and tension
      setting as well as repair in an effort to optimize the function of the
      transplanted hand. Preoperative planning is vital to achieve good functional
      results. We present a case of successful osteosynthesis and side-to-side tendon
      repair, which led to a desirable functional outcome in hand transplantation. 

PMID- 26197155
TI  - The Deltoid Lift: A Cadaveric Analysis and the Literature Review of a Novel
      Surgical Approach to the Proximal Humerus.
AB  - Obtaining adequate exposure of the proximal humerus for anatomic reduction of
      complex intra-articular fractures or in the surgical treatment of tumor may be
      difficult. Here we describe a novel approach to the proximal humerus: the deltoid
      lift, and perform a cadaveric analysis objectively quantifying the exposure. The
      deltoid lift offers significantly greater exposure to the proximal humerus as
      compared with the deltopectoral approach. 

PMID- 26197156
TI  - Total Wrist Fusion Using an Intramedullary Rod Technique With Proximal Row
      Carpectomy.
AB  - Intramedullary pin fixation is a common total wrist fusion technique,
      particularly for patients with rheumatoid arthritis. However, appropriate
      alignment of the proximal carpal row on the carpus can be challenging.
      Inflammatory arthropathy may also degrade the proximal carpal bones to chondral
      shells, retention of which may promote failure of fusion. We describe an
      intramedullary rod technique for total wrist fusion that incorporates a proximal
      row carpectomy. 

PMID- 26197157
TI  - Universal Dorsal Approach of the Wrist.
AB  - The ideal dorsal wrist approach has to provide the best exposure while preserving
      sensitive dorsal nerve branches, dorsal veins, and skin integrity. Longitudinal
      incision is mostly used in the wrist surgery. Few anatomic or clinical studies
      have described transverse dorsal approach following Langer's lines. We present a
      universal transversal skin incision, the design of which meets the requirements
      of a dorsal wrist approach. It is adjustable with the radial and ulnar extension
      and respects Langer's lines, nerves, and veins. We conducted both an anatomic,
      clinical, and a retrospective study. For the anatomic part, we performed a
      cadaveric study on the wrist. For the clinical part of the study, we analyzed
      clinical results for 10 consecutive patients who underwent a universal dorsal
      wrist approach for various surgical procedures by the same surgeon. For the last
      part, we reviewed the patients operated during the past 5 years with this
      approach for different procedures in the wrist. 

PMID- 26197158
TI  - Sexual Function Is Impaired After Common Orthopaedic Nonpelvic Trauma.
AB  - OBJECTIVES: The purpose of this study was to investigate the prevalence and
      longitudinal improvement of patient reported sexual dysfunction after 5 common
      nonpelvic orthopaedic traumatic conditions. DESIGN: Retrospective analysis of
      prospectively collected data. SETTING: Academic Medical Center.
      PATIENTS/PARTICIPANTS: The functional status of 1324 patients with acute proximal
      humerus fractures (n = 104), acute distal radius fractures (n = 396), acute
      tibial plateau fractures (n = 118), acute ankle fractures (n = 434), and chronic
      long bone fracture nonunions (n = 272) was prospectively assessed at baseline, 3,
      6, and 12 months of posttreatment. Patient reported sexual dysfunction, acquired
      from validated functional outcomes surveys, was compared with overall patient
      reported functional outcome for each follow-up visit. Men and women were analyzed
      separately. RESULTS: Sexual dysfunction at the 3-month follow-up was reported in
      31% of proximal humerus fracture patients, 32% of distal radius fracture
      patients, 47% of tibial plateau patients, 11% of ankle fracture patients, and 42%
      of long bone nonunions. By 1-year follow-up, greater than 80% of patients with
      all fracture types reported mild or no sexual dysfunction. Women reported a
      significantly higher degree of sexual dysfunction than men at 6 months (P =
      0.003) and 12 months of follow-up (P = 0.031). CONCLUSIONS: After treatment of
      acute and chronic orthopaedic trauma conditions, a considerable number of
      patients experience sexual dysfunction, with women reporting more dysfunction
      than men. The results of this study should allow orthopaedic trauma surgeons to
      counsel patients regarding expectations of sexual function after traumatic
      orthopaedic conditions. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 26197159
TI  - Synthesis of new 4-phenylpyrimidine-2(1H)-thiones and their potency to inhibit
      COX-1 and COX-2.
AB  - Several new 4-phenylpyrimidine-2(1H)-thiones have been prepared and investigated
      for their potencies to inhibit COX-1 and COX-2 enzymes, and COX-2 expression in
      THP-1 cells. Structure-activity-relationships and physicochemical parameters are
      discussed. Pharmacophore screening and docking studies were carried out for the
      most active compound. 

PMID- 26197160
TI  - Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives.
AB  - With an aim to generate non-toxic, specific and highly potent multidrug
      resistance (MDR) modulators, a novel series of anthranilic acid amide-substituted
      tariquidar derivatives were synthesized. The new compounds were evaluated for
      their cytotoxicity toward normal human colon fibroblasts (CCD18-Co), human
      gastric epithelial cell line (HFE) and primary rat liver cells, and for their
      ability to inhibit P-gp/BCRP-mediated drug efflux and reversal of P-gp and BCRP
      mediated MDR in parental and drug-resistant cancer cell lines (LCC6 MDR1, MCF-7
      FLV1000, R-HepG2, SW620-Ad300). While tariquidar is highly toxic to normal cells,
      the new derivatives exhibited much lower or negligible cytotoxicity. Some of the
      new tariquidar derivatives inhibited both P-gp and BCRP-mediated drug efflux
      whereas a few of them bearing a sulfonamide functional group (1, 5, and 16) are
      specific to P-gp. The new compounds were also found to potentiate the anticancer
      activity of the transporter substrate anticancer drugs in the corresponding
      transporter-overexpressing cell lines. The extent of resistance reversal was
      found to be consistent with the transporter inhibitory effect of the new
      derivatives. To further understand the mechanism of P-gp and BCRP inhibition, the
      tariquidar derivatives were found to interact with the transporters using an
      antibody-based UIC2 or 5D3 shift assay. Moreover, the transporters-inhibiting
      derivatives were found to modulate the ATPase activities of the two MDR
      transporters. Our data thus advocate further development of the new compounds for
      the circumvention of MDR. 

PMID- 26197161
TI  - Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic
      acid analogues as 5-lipoxygenase inhibitors.
AB  - In this work the synthesis, structure-activity relationship (SAR) and biological
      evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO)
      inhibitors are described. The use of structure-guided drug design techniques
      provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2
      and 3.2 MUm in cell-based and cell-free assays, respectively. Optimization of
      binding and functional potencies resulted in the identification of compound 13d,
      which showed an enhanced activity compared to the parent bioactive compound
      caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were
      identified as lead compounds in inhibiting 5-LO products formation in
      neutrophils. Their interference with other targets on the arachidonic acid
      pathway was also assessed. Cytotoxicity tests were performed to exclude a
      relationship between cytotoxicity and the increased activity observed after
      structure optimization. 

PMID- 26197162
TI  - Synthesis and biological evaluation of new curcumin analogues as antioxidant and
      antitumor agents: molecular modeling study.
AB  - New curcumin analogues have been synthesized and their antioxidant activities
      were investigated by measuring their free radical scavenging capacities. The in
      vitro and in vivo antitumor activities of the synthesized compounds on Ehrlich
      ascites carcinoma (EAC) cell line were evaluated. 4-(4-Chlorophenyl)-2-(5-ethyl-7
      (4-methoxybenzylidene)-3-(4-methoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3
      c] pyridin-2-yl)thiazole 7h showed excellent antineoplastic activity in both in
      vitro and in vivo studies more than that of tested compounds and reference drug,
      cisplatin. Different molecular modeling studies were performed, where docking of
      compound 7h into telomerase active site suggested that it could exert its
      antitumor potential by telomerase inhibition. 

PMID- 26197163
TI  - The role of future unpredictability in human risk-taking.
AB  - Models of risk-taking as used in the social sciences may be improved by including
      concepts from life history theory, particularly environmental unpredictability
      and life expectancy. Community college students completed self-report
      questionnaires measuring these constructs along with several well-known
      correlates. The frequency of risk-taking was higher for those with higher future
      unpredictability beliefs and shorter lifespan estimates (as measured by the
      Future Lifespan Assessment developed for this study), and unpredictability
      beliefs remained significant after accounting for standard predictors, such as
      sex and temperament. The results demonstrate the usefulness of applying concepts
      from life history theory to enhance our understanding of human behavior. 

PMID- 26197164
TI  - Life history theory and human reproductive behavior : Environmental/contextual
      influences and heritable variation.
AB  - The purpose of this article is to develop a model of life history theory that
      incorporates environmental influences, contextual influences, and heritable
      variation. I argue that physically or psychologically stressful environments
      delay maturation and the onset of reproductive competence. The social context is
      also important, and here I concentrate on the opportunity for upward social
      mobility as a contextual influence that results in delaying reproduction and
      lowering fertility in the interest of increasing investment in children. I also
      review evidence that variation in life history strategies is influenced by
      genetic variation as well. Finally, I show that cultural shifts in the social
      control of sexual behavior have had differential effects on individuals
      predisposed to high- versus low-investment reproductive strategies. 

PMID- 26197165
TI  - Attachment, mating, and parenting : An evolutionary interpretation.
AB  - A modern evolutionary perspective emphasizing life history theory and behavioral
      ecology is brought to bear on the three core patterns of attachment that are
      identified in studies of infants and young children in the Strange Situation and
      adults using the Adult Attachment Interview. Mating and parenting correlates of
      secure/autonomous, avoidant/dismissing, and resistant/preoccupied attachment
      patterns are reviewed, and the argument is advanced that security evolved to
      promote mutually beneficial interpersonal relations and high investment
      parenting; that avoidant/dismissing attachment evolved to promote opportunistic
      interpersonal relations and low-investment parenting; and that
      resistant/preoccupied attachment evolved to foster "helper-at-the-nest" behavior
      and indirect reproduction. 

PMID- 26197168
TI  - Untitled, Bronx Storefront, "La Rumba Supermarket" : Emilio Sanchez.

PMID- 26197169
TI  - Genomic Technologies Speed Pathogen Detection.

PMID- 26197170
TI  - Back to the Future: Volume as a Quality Metric.

PMID- 26197178
TI  - How the New Neuroscience Will Advance Medicine.

PMID- 26197179
TI  - Competition in the Age of Biosimilars.

PMID- 26197180
TI  - A PIECE OF MY MIND. Learning to Breathe.

PMID- 26197181
TI  - Bystander Interventions Can Improve Outcomes From Out-of-Hospital Cardiac Arrest.

PMID- 26197182
TI  - The Safety of Prescription Drugs.

PMID- 26197183
TI  - Evaluating Research on the Safety of Medical Therapies: The Responsibility of
      Journals to the Health of the Public.

PMID- 26197184
TI  - Effect of Varying Doses of a Monovalent H7N9 Influenza Vaccine With and Without
      AS03 and MF59 Adjuvants on Immune Response: A Randomized Clinical Trial.
AB  - IMPORTANCE: Human infections with the avian influenza A(H7N9) virus were first
      reported in China in 2013 and continue to occur. Hemagglutinin H7 administered
      alone is a poor immunogen necessitating evaluation of adjuvanted H7N9 vaccines.
      OBJECTIVE: To evaluate the immunogenicity and safety of an inactivated H7N9
      vaccine with and without AS03 adjuvant, as well as mixed vaccine schedules that
      included sequential administration of AS03- and MF59-containing formulations and
      of adjuvanted and unadjuvanted formulations. DESIGN, SETTING, AND PARTICIPANTS:
      Double-blind, phase 2 trial at 5 US sites enrolled 980 adults aged 19 through 64
      years from September 2013 through November 2013; safety follow-up was completed
      in January 2015. INTERVENTIONS: The H7N9 vaccine was given on days 0 and 21 at
      nominal doses of 3.75 ug, 7.5 ug, 15 ug, and 45 ug of hemagglutinin with or
      without AS03 or MF59 adjuvant mixed on site. MAIN OUTCOMES AND MEASURES:
      Proportions achieving a hemagglutination inhibition antibody (HIA) titer of 40 or
      higher at 21 days after the second vaccination; vaccine-related serious adverse
      events through 12 months after the first vaccination; and solicited signs and
      symptoms after vaccination through day 7. RESULTS: Two doses of vaccine were
      required to induce detectable antibody titers in most participants. After 2 doses
      of an H7N9 formulation containing 15 ug of hemagglutinin given without adjuvant,
      with AS03 adjuvant, or with MF59 adjuvant, the proportion achieving an HIA titer
      of 40 or higher was 2% (95% CI, 0%-7%) without adjuvant (n = 94), 84% (95% CI,
      76%-91%) with AS03 adjuvant (n = 96), and 57% (95% CI, 47%-68%) with MF59
      adjuvant (n = 92) (P < .001 for comparison of the AS03 and MF59 schedules). The 2
      schedules alternating AS03-and MF59-adjuvanted formulations led to lower
      geometric mean titers (GMTs) of (41.5 [95% CI, 31.7-54.4]; n = 92) and (58.6 [95%
      CI, 44.3-77.6]; n = 96) than the group induced by 2 AS03-adjuvanted formulations
      (n = 96) (103.4 [95% CI, 78.7-135.9]; P < .001) but higher GMTs than 2 doses of
      MF59-adjuvanted formulation (n = 94) (29.0 [95% CI, 22.4-37.6]; P < .001).
      CONCLUSIONS AND RELEVANCE: The AS03 and MF59 adjuvants augmented the immune
      responses to 2 doses of an inactivated H7N9 influenza vaccine, with AS03
      adjuvanted formulations inducing the highest titers. This study of 2 adjuvants
      used in influenza vaccine formulations with adjuvant mixed on site provides
      immunogenicity information that may be informative to influenza pandemic
      preparedness programs. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01942265.

PMID- 26197185
TI  - Association of Bystander Interventions With Neurologically Intact Survival Among
      Patients With Bystander-Witnessed Out-of-Hospital Cardiac Arrest in Japan.
AB  - IMPORTANCE: Neurologically intact survival after out-of-hospital cardiac arrest
      (OHCA) has been increasing in Japan. However, associations between increased
      prehospital care, including bystander interventions and increases in survival,
      have not been well estimated. OBJECTIVE: To estimate the associations between
      bystander interventions and changes in neurologically intact survival among
      patients with OHCA in Japan. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
      descriptive study using data from Japan's nationwide OHCA registry, which started
      in January 2005. The registry includes all patients with OHCA transported to the
      hospital by emergency medical services (EMS) and recorded patients'
      characteristics, prehospital interventions, and outcomes. Participants were
      167,912 patients with bystander-witnessed OHCA of presumed cardiac origin in the
      registry between January 2005 and December 2012. EXPOSURES: Prehospital
      interventions by bystander, including defibrillation using public-access
      automated external defibrillators and chest compression. MAIN OUTCOMES AND
      MEASURES: Neurologically intact survival was defined as Glasgow-Pittsburgh
      cerebral performance category score 1 or 2 and overall performance category
      scores 1 or 2 at 1 month or at discharge. The association between the
      interventions and neurologically intact survival was evaluated. RESULTS: From
      2005 to 2012, the number of bystander-witnessed OHCAs of presumed cardiac origin
      increased from 17,882 (14.0 per 100,000 persons [95% CI, 13.8-14.2]) to 23,797
      (18.7 per 100,000 persons [95% CI, 18.4-18.9]), and neurologically intact
      survival increased from 587 cases (age-adjusted proportion, 3.3% [95% CI, 3.0%
      3.5%]) to 1710 cases (8.2% [95% CI, 7.8%-8.6%]). The rates of bystander chest
      compression increased from 38.6% to 50.9%, bystander-only defibrillation
      increased from 0.1% to 2.3%, bystander defibrillation combined with EMS
      defibrillation increased from 0.1% to 1.4%, and EMS-only defibrillation decreased
      from 26.6% to 23.5%. Performance of bystander chest compression, compared with no
      bystander chest compression, was associated with increased neurologically intact
      survival (8.4% [6594 survivors/78,592 cases] vs 4.1% [3595 survivors/88,720
      cases]; odds ratio [OR], 1.52 [95% CI, 1.45-1.60]). Compared with EMS-only
      defibrillation (15.0% [6445 survivors/42,916 cases]), bystander-only
      defibrillation (40.7% [931 survivors/2287 cases]) was associated with increased
      neurologically intact survival (OR, 2.24 [95% CI, 1.93-2.61]), as was combined
      bystander and EMS defibrillation (30.5% [444 survivors/1456 cases]; OR, 1.50 [95%
      CI, 1.31-1.71]), whereas no defibrillation (2.0% [2369 survivors/120,653 cases])
      was associated with reduced survival (OR, 0.43 [95% CI, 0.39-0.48]). CONCLUSIONS
      AND RELEVANCE: In Japan, between 2005 and 2012, the rates of bystander chest
      compression and bystander defibrillation increased and were associated with
      increased odds of neurologically intact survival.

PMID- 26197186
TI  - Association of Bystander and First-Responder Intervention With Survival After Out
      of-Hospital Cardiac Arrest in North Carolina, 2010-2013.
AB  - IMPORTANCE: Out-of-hospital cardiac arrest is associated with low survival, but
      early cardiopulmonary resuscitation (CPR) and defibrillation can improve outcomes
      if more widely adopted. OBJECTIVE: To examine temporal changes in bystander and
      first-responder resuscitation efforts before arrival of the emergency medical
      services (EMS) following statewide initiatives to improve bystander and first
      responder efforts in North Carolina from 2010-2013 and to examine the association
      between bystander and first-responder resuscitation efforts and survival and
      neurological outcome. DESIGN, SETTINGS, AND PARTICIPANTS: We studied 4961
      patients with out-of-hospital cardiac arrest for whom resuscitation was attempted
      and who were identified through the Cardiac Arrest Registry to Enhance Survival
      (2010-2013). First responders were dispatched police officers, firefighters,
      rescue squad, or life-saving crew trained to perform basic life support until
      arrival of the EMS. EXPOSURES: Statewide initiatives to improve bystander and
      first-responder interventions included training members of the general population
      in CPR and in use of automated external defibrillators (AEDs), training first
      responders in team-based CPR including AED use and high-performance CPR, and
      training dispatch centers in recognition of cardiac arrest. MAIN OUTCOMES AND
      MEASURES: The proportion of bystander and first-responder resuscitation efforts,
      including the combination of efforts between bystanders and first responders,
      from 2010 through 2013 and the association between these resuscitation efforts
      and survival and neurological outcome. RESULTS: The combination of bystander CPR
      and first-responder defibrillation increased from 14.1% (51 of 362; 95% CI, 10.9%
      18.1%) in 2010 to 23.1% (104 of 451; 95% CI, 19.4%-27.2%) in 2013 (P < .01).
      Survival with favorable neurological outcome increased from 7.1% (82 of 1149; 95%
      CI, 5.8%-8.8%) in 2010 to 9.7% (129 of 1334; 95% CI, 8.2%-11.4%) in 2013 (P =
      .02) and was associated with bystander-initiated CPR. Adjusting for age and sex,
      bystander and first-responder interventions were associated with higher survival
      to hospital discharge. Survival following EMS-initiated CPR and defibrillation
      was 15.2% (30 of 198; 95% CI, 10.8%-20.9%) compared with 33.6% (38 of 113; 95%
      CI, 25.5%-42.9%) following bystander-initiated CPR and defibrillation (odds ratio
      [OR], 3.12; 95% CI, 1.78-5.46); 24.2% (83 of 343; 95% CI, 20.0%-29.0%) following
      bystander CPR and first-responder defibrillation (OR, 1.70; 95% CI, 1.06-2.71);
      and 25.2% (109 of 432; 95% CI, 21.4%-29.6%) following first-responder CPR and
      defibrillation (OR, 1.77; 95% CI, 1.13-2.77). CONCLUSIONS AND RELEVANCE:
      Following a statewide educational intervention on rescusitation training, the
      proportion of patients receiving bystander-initiated CPR and defibrillation by
      first responders increased and was associated with greater likelihood of
      survival. Bystander-initiated CPR was associated with greater likelihood of
      survival with favorable neurological outcome.

PMID- 26197187
TI  - Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons
      With Diabetes.
AB  - IMPORTANCE: Studies suggest pioglitazone use may increase risk of cancers.
      OBJECTIVE: To examine whether pioglitazone use for diabetes is associated with
      risk of bladder and 10 additional cancers. DESIGN, SETTING, AND PARTICIPANTS:
      Cohort and nested case-control analyses among persons with diabetes. A bladder
      cancer cohort followed 193,099 persons aged 40 years or older in 1997-2002 until
      December 2012; 464 case patients and 464 matched controls were surveyed about
      additional confounders. A cohort analysis of 10 additional cancers included
      236,507 persons aged 40 years or older in 1997-2005 and followed until June 2012.
      Cohorts were from Kaiser Permanente Northern California. EXPOSURES: Ever use,
      duration, cumulative dose, and time since initiation of pioglitazone as time
      dependent. MAIN OUTCOMES AND MEASURES: Incident cancer, including bladder,
      prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma,
      pancreas, kidney/renal pelvis, rectum, and melanoma. RESULTS: Among 193,099
      persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median
      duration, 2.8 years; range, 0.2-13.2 years) and 1261 had incident bladder cancer.
      Crude incidences of bladder cancer in pioglitazone users and nonusers were 89.8
      and 75.9 per 100,000 person-years, respectively. Ever use of pioglitazone was not
      associated with bladder cancer risk (adjusted hazard ratio [HR], 1.06; 95% CI,
      0.89-1.26). Results were similar in case-control analyses (pioglitazone use:
      19.6% among case patients and 17.5% among controls; adjusted odds ratio, 1.18;
      95% CI, 0.78-1.80). In adjusted analyses, there was no association with 8 of the
      10 additional cancers; ever use of pioglitazone was associated with increased
      risk of prostate cancer (HR, 1.13; 95% CI, 1.02-1.26) and pancreatic cancer (HR,
      1.41; 95% CI, 1.16-1.71). Crude incidences of prostate and pancreatic cancer in
      pioglitazone users vs nonusers were 453.3 vs 449.3 and 81.1 vs 48.4 per 100,000
      person-years, respectively. No clear patterns of risk for any cancer were
      observed for time since initiation, duration, or dose. CONCLUSIONS AND RELEVANCE:
      Pioglitazone use was not associated with a statistically significant increased
      risk of bladder cancer, although an increased risk, as previously observed, could
      not be excluded. The increased prostate and pancreatic cancer risks associated
      with ever use of pioglitazone merit further investigation to assess whether they
      are causal or are due to chance, residual confounding, or reverse causality.

PMID- 26197188
TI  - Treatment of Atrial Fibrillation.
AB  - IMPORTANCE: Atrial fibrillation is a common arrhythmia that affects more than 2.5
      million people in the United States and causes substantial morbidity and
      mortality, especially regarding the increased risk of stroke. OBJECTIVE: To
      summarize atrial fibrillation treatment exclusive of stroke prevention. EVIDENCE
      REVIEW: An Ovid MEDLINE comprehensive literature search was performed on atrial
      fibrillation therapy excluding anticoagulation and emphasizing studies published
      within the last 5 years through April 2015 (N = 5044 references). The 2014 atrial
      fibrillation guideline from the American Heart Association, the American College
      of Cardiology, and the Heart Rhythm Society also was reviewed. FINDINGS:
      Reversible causes of atrial fibrillation should be identified. Risk factor
      modification, including weight loss and treatment of hypertension, diabetes, and
      obstructive sleep apnea can reduce atrial fibrillation episodes. Appropriate
      anticoagulation is necessary for patients at substantial stroke risk regardless
      of rate or rhythm treatment strategy. Sinus rhythm is often needed to control
      symptoms; however, an alternative strategy for atrial fibrillation is appropriate
      rate control. Rate control is safe in older patients (those who are about age
      >=65 years) followed up for a few years, but no such safety data exist for
      patients younger than 60 years or for those followed up for longer periods. Thus,
      selection of therapy is individualized, taking into account present and future
      medical problems for the patient. Choice of an antiarrhythmic drug is based on
      safety first vs efficacy. Catheter ablation is an effective nonpharmacological
      alternative that is often, but not always, the second-line treatment. Reduction
      of the frequency and duration of atrial fibrillation episodes that result in a
      significant improvement in quality of life is a good marker of drug treatment
      success and complete elimination of atrial fibrillation is not required in many
      patients. Rate control is usually achieved with a beta-blocker or non
      dihydropyridine calcium channel blockers. It is important to assess adequate rate
      control during both rest and activity. If the ventricular rate goes uncontrolled
      for a prolonged period, tachycardia-mediated cardiomyopathy can occur.
      CONCLUSIONS AND RELEVANCE: Therapy for atrial fibrillation includes prevention
      and modification of inciting causes and appropriate anticoagulation. Rate control
      is necessary for all patients. Maintenance of sinus rhythm with drugs or catheter
      ablation should be considered based on the individual needs of each patient.

PMID- 26197189
TI  - Care Bundles and Prevention of Surgical Site Infection in Colorectal Surgery.

PMID- 26197190
TI  - Management of Anticoagulation in Patients With Atrial Fibrillation.

PMID- 26197191
TI  - Change in International Normalized Ratio Among Patients Treated With
      Dicloxacillin and Vitamin K Antagonists.

PMID- 26197192
TI  - Single-Gene Genotyping and Personalized Preventive Care.

PMID- 26197193
TI  - Single-Gene Genotyping and Personalized Preventive Care--Reply.

PMID- 26197194
TI  - Single-Gene Genotyping and Personalized Preventive Care--Reply.

PMID- 26197195
TI  - Exemptions to Vaccination for Children.

PMID- 26197196
TI  - Exemptions to Vaccination for Children--Reply.

PMID- 26197198
TI  - New Opportunities in Health Broadcasting.

PMID- 26197199
TI  - JAMA PATIENT PAGE. Preventing Stroke in People With Atrial Fibrillation.

PMID- 26197200
TI  - Nanometric Graphene Oxide Framework Membranes with Enhanced Heavy Metal Removal
      via Nanofiltration.
AB  - A novel dual-modification strategy, including (1) the cross-linking and
      construction of a GO framework by ethylenediamine (EDA) and (2) the amine
      enrichment modification by hyperbranched polyethylenimine (HPEI), has been
      proposed to design stable and highly charged GO framework membranes with the GO
      selective layer thickness of 70 nm for effective heave metal removal via
      nanofiltration (NF). Results from sonication experiments and positron
      annihilation spectroscopy confirmed that EDA cross-linking not only enhanced
      structural stability but also enlarged the nanochannels among the laminated GO
      nanosheets for higher water permeability. HPEI 60K was found to be the most
      effective post-treatment agent that resulted in GO framework membranes with a
      higher surface charge and lower transport resistance. The newly developed
      membrane exhibited a high pure water permeability of 5.01 L m(-2) h(-1) bar(-1)
      and comparably high rejections toward Mg(2+), Pb(2+), Ni(2+), Cd(2+), and Zn(2+).
      These results have demonstrated the great potential of GO framework materials in
      wastewater treatment and may provide insights for the design and fabrication of
      the next generation two-dimensional (2D)-based NF membranes.

PMID- 26197201
TI  - Water and solute transport across the peritoneal membrane.
AB  - PURPOSE OF REVIEW: We review the molecular mechanisms of peritoneal transport and
      discuss how a better understanding of these mechanisms is relevant for dialysis
      therapy. RECENT FINDINGS: Peritoneal dialysis involves diffusion and osmosis
      through the highly vascularized peritoneal membrane. Computer simulations,
      expression studies and functional analyses in Aqp1 knockout mice demonstrated the
      critical role of the water channel aquaporin-1 (AQP1) in water removal during
      peritoneal dialysis. Pharmacologic regulation of AQP1, either through increased
      expression or gating, is associated with increased water transport in rodent
      models of peritoneal dialysis. Water transport is impaired during acute
      peritonitis, despite unchanged expression of AQP1, resulting from the increased
      microvascular area that dissipates the osmotic gradient across the membrane. In
      long-term peritoneal dialysis patients, the fibrotic interstitium also impairs
      water transport, resulting in ultrafiltration failure. Recent data suggest that
      stroke and drug intoxications might benefit from peritoneal dialysis and could
      represent novel applications of peritoneal transport in the future. SUMMARY: A
      better understanding of the regulation of osmotic water transport across the
      peritoneum offers novel insights into the role of water channels in microvascular
      endothelia, the functional importance of structural changes in the peritoneal
      interstitium and the transport of water and solutes across biological membranes
      in general.

PMID- 26197202
TI  - Pharmacologic inhibition of intestinal sodium uptake: a gut centric approach to
      sodium management.
AB  - PURPOSE OF REVIEW: Impaired sodium excretion in patients with chronic kidney
      disease (CKD) can drive fluid overload and hypertension and accelerate CKD
      progression. Diuretics reduce fluid overload but require residual kidney function
      to work. Adherence to dietary sodium restriction is generally poor. Here, we
      review an alternative pharmacologic strategy aimed at reducing sodium absorption
      from the gut. RECENT FINDINGS: Genetic studies implicate the sodium/hydrogen
      exchanger isoform 3 (NHE3) as the major absorptive sodium transporter.
      Pharmacologic inhibition of apically expressed gut NHE3 offers the potential of
      reducing sodium absorption and fluid overload independent of kidney function and
      with better safety than systemic drugs. Two small-molecule inhibitors of NHE3
      (tenapanor and SAR218034) with minimal systemic exposure reduce urinary sodium
      and increase stool sodium in a dose-dependent manner in rodents, with similar
      results observed with tenapanor in humans. These molecules also reduce blood
      pressure in rat models of CKD (tenapanor) and hypertension (SAR218034). Clinical
      trials of tenapanor in patients with CKD-related disorders are ongoing. SUMMARY:
      Pharmacologic inhibition of gut NHE3 may be a viable strategy for managing sodium
      load in patients with CKD or with sodium-sensitive hypertension in general.
      Ongoing clinical trials will shed further light on the potential benefits of this
      approach.

PMID- 26197204
TI  - Higher-Resolution Magnetic Resonance Elastography in Meningiomas to Determine
      Intratumoral Consistency.
AB  - BACKGROUND: Magnetic resonance elastography (MRE) analyzes shear wave movement
      through tissue to determine stiffness. In a prior study, measurements with first
      generation brain MRE techniques correlated with intraoperative observations of
      overall meningioma stiffness. OBJECTIVE: To evaluate the diagnostic accuracy of a
      higher-resolution MRE technique to preoperatively detect intratumoral variations
      compared with surgeon assessment. METHODS: Fifteen meningiomas in 14 patients
      underwent MRE. Tumors with regions of distinctly different stiffness were
      considered heterogeneous. Intratumoral portions were considered hard if there was
      a significant area >=6 kPa. A 5-point scale graded intraoperative consistency. A
      durometer semiquantitatively measured surgical specimen hardness. Statistics
      included chi, sensitivity, specificity, positive and negative predicative values,
      and Spearman rank correlation coefficient. RESULTS: For MRE and surgery, 9 (60%)
      and 7 (47%) tumors were homogeneous, 6 (40%) and 8 (53%) tumors were
      heterogeneous, 6 (40%) and 10 (67%) tumors had hard portions, and 14 (93%) and 12
      (80%) tumors had soft portions, respectively. MRE sensitivity, specificity, and
      positive and negative predictive values were as follows: for heterogeneity, 75%,
      100%, 100%, and 87%; for hardness, 60%, 100%, 100%, and 56%; and for softness,
      100%, 33%, 86%, and 100%. Overall, 10 tumors (67%) matched well with MRE and
      intraoperative consistency and correlated between intraoperative observations (P
      = .02) and durometer readings (P = .03). Tumor size <=3.5 cm or vascular tumors
      were more likely to be inconsistent (P < .05). CONCLUSION: MRE was excellent at
      ruling in heterogeneity with hard portions but less effective in ruling out
      heterogeneity and hard portions, particularly in tumors more vascular or <3.5 cm.
      MRE is the first technology capable of prospectively evaluating intratumoral
      stiffness and, with further refinement, will likely prove useful in preoperative
      planning.

PMID- 26197205
TI  - Commentary: Occipital Nerve Stimulation for the Treatment of Patients With
      Medically Refractory Occipital Neuralgia.

PMID- 26197203
TI  - Redox signaling, Nox5 and vascular remodeling in hypertension.
AB  - PURPOSE OF REVIEW: Extensive data indicate a role for reactive oxygen species
      (ROS) and redox signaling in vascular damage in hypertension. However, molecular
      mechanisms underlying these processes remain unclear, but oxidative post
      translational modification of vascular proteins is critical. This review
      discusses how proteins are oxidatively modified and how redox signaling
      influences vascular smooth muscle cell growth and vascular remodeling in
      hypertension. We also highlight Nox5 as a novel vascular ROS-generating oxidase.
      RECENT FINDINGS: Oxidative stress in hypertension leads to oxidative imbalance
      that affects vascular cell function through redox signaling. Many Nox isoforms
      produce ROS in the vascular wall, and recent findings show that Nox5 may be
      important in humans. ROS regulate signaling by numerous processes including
      cysteine oxidative post-translational modification such as S-nitrosylation, S
      glutathionylation and sulfydration. In vascular smooth muscle cells, this
      influences cellular responses to oxidative stimuli promoting changes from a
      contractile to a proliferative phenotype. SUMMARY: In hypertension, Nox-induced
      ROS production is increased, leading to perturbed redox signaling through
      oxidative modifications of vascular proteins. This influences mitogenic signaling
      and cell cycle regulation, leading to altered cell growth and vascular remodeling
      in hypertension.

PMID- 26197206
TI  - Commentary: Occipital Nerve Stimulation for the Treatment of Patients With
      Medically Refractory Occipital Neuralgia.

PMID- 26197207
TI  - Synthesis of Normorphans through an Efficient Intramolecular Carbamoylation of
      Ketones.
AB  - An unexpected C-C bond cleavage was observed in trichloroacetamide-tethered
      ketones under amine treatment and exploited to develop a new synthesis of
      normophans from 4-amidocyclohexanones. The reaction involves an unprecedented
      intramolecular haloform-type reaction of trichloroacetamides promoted by enamines
      (generated in situ from ketones) as counter-reagents. The methodology was applied
      to the synthesis of compounds embodying the 6-azabicyclo[3.2.1]octane framework. 

PMID- 26197208
TI  - Perceiving emotions: Cueing social categorization processes and attentional
      control through facial expressions.
AB  - Individuals spontaneously categorise other people on the basis of their gender,
      ethnicity and age. But what about the emotions they express? In two studies we
      tested the hypothesis that facial expressions are similar to other social
      categories in that they can function as contextual cues to control attention. In
      Experiment 1 we associated expressions of anger and happiness with specific
      proportions of congruent/incongruent flanker trials. We also created consistent
      and inconsistent category members within each of these two general contexts. The
      results demonstrated that participants exhibited a larger congruency effect when
      presented with faces in the emotional group associated with a high proportion of
      congruent trials. Notably, this effect transferred to inconsistent members of the
      group. In Experiment 2 we replicated the effects with faces depicting true and
      false smiles. Together these findings provide consistent evidence that
      individuals spontaneously utilise emotions to categorise others and that such
      categories determine the allocation of attentional control.

PMID- 26197209
TI  - Synthetic modeling chemistry of iron-sulfur clusters in nitric oxide signaling.
AB  - Nitric oxide (NO) is an important signaling molecule that is involved in many
      physiological and pathological functions. Iron-sulfur proteins are one of the
      main reaction targets for NO, and the [Fe-S] clusters within these proteins are
      converted to various iron nitrosyl species upon reaction with NO, of which
      dinitrosyl iron complexes (DNICs) are the most prevalent. Much progress has been
      made in identifying the origin of cellular DNIC generation. However, it is not
      well-understood which other products besides DNICs may form during [Fe-S] cluster
      degradation nor what effects DNICs and other degradation products can have once
      they are generated in cells. Even more elusive is an understanding of the manner
      by which cells cope with unwanted [Fe-S] modifications by NO. This Account
      describes our synthetic modeling efforts to identify cluster degradation products
      derived from the [2Fe-2S]/NO reaction in order to establish their chemical
      reactivity and repair chemistry. Our intent is to use the chemical knowledge that
      we generate to provide insight into the unknown biological consequences of
      cluster modification. Our recent advances in three different areas are described.
      First, new reaction conditions that lead to the formation of previously
      unrecognized products during the reaction of [Fe-S] clusters with NO are
      identified. Hydrogen sulfide (H2S), a gaseous signaling molecule, can be
      generated from the reaction between [2Fe-2S] clusters and NO in the presence of
      acid or formal H* (e(-)/H(+)) donors. In the presence of acid, a mononitrosyl
      iron complex (MNIC) can be produced as the major iron-containing product. Second,
      cysteine analogues can efficiently convert MNICs back to [2Fe-2S] clusters
      without the need for any other reagents. This reaction is possible for cysteine
      analogues because of their ability to labilize NO from MNICs and their capacity
      to undergo C-S bond cleavage, providing the necessary sulfide for [2Fe-2S]
      cluster formation. Lastly, unique dioxygen reactivity of various types of DNICs
      has been established. N-bound neutral {Fe(NO)2}(10) DNICs react with O2 to
      generate low-temperature stable peroxynitrite (ONOO(-)) species, which then carry
      out nitration chemistry in the presence of phenolic substrates, relevant to
      tyrosine nitration chemistry. The reaction between S-bound anionic {Fe(NO)2}(9)
      DNICs and O2 results in the formation of Roussin's red esters (RREs) and thiol
      oxidation products, chemistry that may be important in biological cysteine
      oxidation. The N-bound cationic {Fe(NO)2}(9) DNICs can spontaneously release NO,
      and this property can be utilized in developing a new class of NO-donating agents
      with anti-inflammatory activity. 

PMID- 26197210
TI  - Ribavirin for Chronic Hepatitis Prevention among Patients with Hematologic
      Malignancies.
AB  - Findings among a cohort of 26 patients who had hematologic malignancies and
      hepatitis E virus (HEV) infection support that HEV can induce chronic hepatitis.
      However, a 3-month course of ribavirin can induce a rapid viral clearance,
      reducing the risk for chronic hepatitis and enabling continuation of cytotoxic
      treatments for underlying malignancies. 

PMID- 26197211
TI  - Why do infections cause cancer?

PMID- 26197212
TI  - Impact of obesity on the risk of wound infection following surgery: results from
      a nationwide prospective multicentre cohort study in England.
AB  - We sought to assess the impact of body mass index on the risk of surgical site
      infection in a prospective cohort study of 206 National Health Service (NHS)
      hospitals in England between 2007 and 2011. Body mass index was available for
      159,720 of 350,089 operations among patients undergoing abdominal hysterectomy,
      coronary artery bypass graft, hip replacement, knee replacement, or large-bowel
      surgery. Among these patients, the risk of surgical site infection ranged from
      0.65% for knee replacement to 11.04% for large-bowel surgery. Overall, 127,512
      (79.8%) patients were overweight or obese (body mass index of >=25 kg/m(2)).
      Obesity was associated with a 1.1-fold to 4.4-fold increase in the adjusted odds
      of developing surgical site infection as compared with normal weight, depending
      on the type of surgery. The population-attributable fraction (PAF) for body mass
      index was greatest in overweight (body mass index of 25.0-29.9 kg/m(2)) patients
      undergoing coronary artery bypass graft, accounting for 15% of their overall risk
      of surgical site infection (PAF 0.15; 95% CI 0.09-0.22). Being overweight or
      obese substantially increased the likelihood of patients developing surgical site
      infection. Given the increasingly high proportion of the surgical population who
      are overweight, this is likely to place a considerable additional burden on the
      NHS. Strategies for mitigating this excess risk need to be found.

PMID- 26197213
TI  - Immunodeficiency-associated viral oncogenesis.
AB  - Several viruses with different replication mechanisms contribute to oncogenesis
      by both direct and indirect mechanisms in immunosuppressed subjects after solid
      organ transplantation, after allogeneic stem cell transplantation, or with human
      immunodeficiency virus (HIV) infection. Epstein-Barr virus (EBV), human
      papillomavirus (HPV), Kaposi sarcoma herpesvirus (KSHV), human T-cell
      lymphotropic virus type 1 (HTLV-1) and Merkel cell polyoma virus (MCV) are the
      main viruses associated with the development of cancer in immunosuppressed
      patients. Besides being a main cause of immunodeficiency, HIV1 has a direct pro
      oncogenic effect. In this review, we provide an update on the association between
      the condition of acquired immunodeficiency and cancer risk, specifically
      addressing the contributions to oncogenesis of HPV, MCV, KSHV, HTLV-1, and EBV. 

PMID- 26197215
TI  - Enhanced Third-Harmonic Generation from a Metal/Semiconductor Core/Shell Hybrid
      Nanostructure.
AB  - Nonlinear optical processes can be dramatically enhanced via the use of localized
      surface plasmon modes in metal nanoparticles. Here we show how more elaborate
      structures, based on shape-controlled Au/Cu2O core/shell nanostructures, enable
      further enhancement of the nanoparticle third-harmonic scattering cross-section.
      The semiconducting component takes a twofold role in this structure, both
      providing a knob to tune the resonant frequency of the gold plasmon and providing
      resonant enhancement by virtue of its excitonic states. The advantages and
      deficiencies of using such core/shell metal/semiconductor structures are
      discussed. 

PMID- 26197214
TI  - Minocycline activity against clinical isolates of multidrug-resistant
      Acinetobacter baumannii.

PMID- 26197216
TI  - Palladium-Catalyzed ortho-Olefination of Phenyl Acetic and Phenyl Propylacetic
      Esters via C-H Bond Activation.
AB  - A highly regioselective palladium-catalyzed ester-directed ortho-olefination of
      phenyl acetic and propionic esters with olefins via C-H bond activation has been
      developed. A wide variety of phenyl acetic and propionic esters were tolerated in
      this transformation, affording the corresponding olefinated aromatic compounds.
      The ortho-olefination of heterocyclic acetic and propionic esters also took place
      smoothly giving the products in good yields, thus proving the potential utility
      of this protocol in synthetic chemistry. 

PMID- 26197217
TI  - Application of Whole Exome Sequencing in Six Families with an Initial Diagnosis
      of Autosomal Dominant Retinitis Pigmentosa: Lessons Learned.
AB  - This study aimed to identify the genetics underlying dominant forms of inherited
      retinal dystrophies using whole exome sequencing (WES) in six families
      extensively screened for known mutations or genes. Thirty-eight individuals were
      subjected to WES. Causative variants were searched among single nucleotide
      variants (SNVs) and insertion/deletion variants (indels) and whenever no
      potential candidate emerged, copy number variant (CNV) analysis was performed.
      Variants or regions harboring a candidate variant were prioritized and
      segregation of the variant with the disease was further assessed using Sanger
      sequencing in case of SNVs and indels, and quantitative PCR (qPCR) for CNVs. SNV
      and indel analysis led to the identification of a previously reported mutation in
      PRPH2. Two additional mutations linked to different forms of retinal dystrophies
      were identified in two families: a known frameshift deletion in RPGR, a gene
      responsible for X-linked retinitis pigmentosa and p.Ser163Arg in C1QTNF5
      associated with Late-Onset Retinal Degeneration. A novel heterozygous deletion
      spanning the entire region of PRPF31 was also identified in the affected members
      of a fourth family, which was confirmed with qPCR. This study allowed the
      identification of the genetic cause of the retinal dystrophy and the
      establishment of a correct diagnosis in four families, including a large
      heterozygous deletion in PRPF31, typically considered one of the pitfalls of this
      method. Since all findings in this study are restricted to known genes, we
      propose that targeted sequencing using gene-panel is an optimal first approach
      for the genetic screening and that once known genetic causes are ruled out, WES
      might be used to uncover new genes involved in inherited retinal dystrophies.

PMID- 26197219
TI  - Developmental and Persistent Toxicities of Maternally Deposited Selenomethionine
      in Zebrafish (Danio rerio).
AB  - The objectives of this study were (1) to establish egg selenium (Se) toxicity
      thresholds for mortality and deformities in early life stages of zebrafish (Danio
      rerio) after exposure to excess selenomethionine (SeMet, the dominant chemical
      species of Se in diets) via in ovo maternal transfer and (2) to investigate the
      persistent effects of developmental exposure to excess SeMet on swim performance
      and metabolic capacities in F1-generation adult zebrafish. Adult zebrafish were
      fed either control food (1.3 MUg Se/g, dry mass or d.m.) or food spiked with
      increasing measured concentrations of Se (3.4, 9.8, or 27.5 MUg Se/g, d.m.) in
      the form of SeMet for 90 d. In ovo exposure to SeMet increased mortality and
      deformities in larval zebrafish in a concentration-dependent fashion with
      threshold egg Se concentrations (EC10s) of 7.5 and 7.0 MUg Se/g d.m.,
      respectively. Impaired swim performance and greater respiration and metabolic
      rates were observed in F1-generation zebrafish exposed in ovo to 6.8 and 12.7 MUg
      Se/g d.m and raised to adulthood in clean water. A species sensitivity
      distribution (SSD) based on egg Se developmental toxicity thresholds suggests
      that zebrafish are the most sensitive fish species studied to date. 

PMID- 26197218
TI  - One Year of Glaucoma Research in Review-2013 to 2014.
AB  - PURPOSE: The purpose of this study was to provide the practicing clinical
      ophthalmologist with an update on relevant glaucoma literature published from
      2013 to 2014. DESIGN: This study is a literature review. METHODS: The authors
      conducted a 1-year (October 1, 2013, to September 30, 2014) English-language
      glaucoma literature search on PubMed of articles containing "glaucoma" or
      "glaucomatous" with title/abstract as a filter. Medical subject headings filtered
      searching was not performed because of the newness of the reviewed material.
      RESULTS: Literature search yielded 2314 articles, after which we excluded reviews
      and letters to the editor. We highlighted articles featuring new or updated
      approaches to the pathophysiology, diagnosis, or treatment of glaucoma and gave
      preference to human research. CONCLUSIONS: This review features literature that
      is of interest to ophthalmologists in practice and also highlights studies that
      may provide insight on future developments applicable to clinical ophthalmology.

PMID- 26197220
TI  - Size Distribution Imaging by Non-Uniform Oscillating-Gradient Spin Echo (NOGSE)
      MRI.
AB  - Objects making up complex porous systems in Nature usually span a range of sizes.
      These size distributions play fundamental roles in defining the physicochemical,
      biophysical and physiological properties of a wide variety of systems - ranging
      from advanced catalytic materials to Central Nervous System diseases. Accurate
      and noninvasive measurements of size distributions in opaque, three-dimensional
      objects, have thus remained long-standing and important challenges. Herein we
      describe how a recently introduced diffusion-based magnetic resonance
      methodology, Non-Uniform-Oscillating-Gradient-Spin-Echo (NOGSE), can determine
      such distributions noninvasively. The method relies on its ability to probe
      confining lengths with a (length)6 parametric sensitivity, in a constant-time,
      constant-number-of-gradients fashion; combined, these attributes provide
      sufficient sensitivity for characterizing the underlying distributions in MUm
      scaled cellular systems. Theoretical derivations and simulations are presented to
      verify NOGSE's ability to faithfully reconstruct size distributions through
      suitable modeling of their distribution parameters. Experiments in yeast cell
      suspensions - where the ground truth can be determined from ancillary microscopy 
      corroborate these trends experimentally. Finally, by appending to the NOGSE
      protocol an imaging acquisition, novel MRI maps of cellular size distributions
      were collected from a mouse brain. The ensuing micro-architectural contrasts
      successfully delineated distinctive hallmark anatomical sub-structures, in both
      white matter and gray matter tissues, in a non-invasive manner. Such findings
      highlight NOGSE's potential for characterizing aberrations in cellular size
      distributions upon disease, or during normal processes such as development.

PMID- 26197221
TI  - Sample Selection for Training Cascade Detectors.
AB  - Automatic detection systems usually require large and representative training
      datasets in order to obtain good detection and false positive rates. Training
      datasets are such that the positive set has few samples and/or the negative set
      should represent anything except the object of interest. In this respect, the
      negative set typically contains orders of magnitude more images than the positive
      set. However, imbalanced training databases lead to biased classifiers. In this
      paper, we focus our attention on a negative sample selection method to properly
      balance the training data for cascade detectors. The method is based on the
      selection of the most informative false positive samples generated in one stage
      to feed the next stage. The results show that the proposed cascade detector with
      sample selection obtains on average better partial AUC and smaller standard
      deviation than the other compared cascade detectors.

PMID- 26197222
TI  - A Mixed Kijima Model Using the Weibull-Based Generalized Renewal Processes.
AB  - Generalized Renewal Processes are useful for approaching the rejuvenation of
      dynamical systems resulting from planned or unplanned interventions. We present
      new perspectives for the Generalized Renewal Processes in general and for the
      Weibull-based Generalized Renewal Processes in particular. Disregarding from
      literature, we present a mixed Generalized Renewal Processes approach involving
      Kijima Type I and II models, allowing one to infer the impact of distinct
      interventions on the performance of the system under study. The first and second
      theoretical moments of this model are introduced as well as its maximum
      likelihood estimation and random sampling approaches. In order to illustrate the
      usefulness of the proposed Weibull-based Generalized Renewal Processes model,
      some real data sets involving improving, stable, and deteriorating systems are
      used.

PMID- 26197223
TI  - New effects of GABAB receptor allosteric modulator rac-BHFF on ambient GABA,
      uptake/release, Em and synaptic vesicle acidification in nerve terminals.
AB  - Positive allosteric modulators of GABAB receptors have great therapeutic
      potential for medications of anxiety, depression, etc. The effects of recently
      discovered modulator rac-BHFF on the key characteristics of GABAergic
      neurotransmission were investigated in cortical and hippocampal presynaptic nerve
      terminals of rats (synaptosomes). The ambient level of [(3)H]GABA that is a
      balance between release and uptake of the neurotransmitter increased
      significantly in the presence of rac-BHFF (at concentrations 10-30MUM). The
      initial velocity of synaptosomal [(3)H]GABA uptake was suppressed by the
      modulator. In the presence of GABA transporter blocker NO-711, it was shown that
      rac-BHFF increased tonic release of [(3)H]GABA from synaptosomes (at
      concentrations 3-30MUM). Rac-BHFF within the concentration range of 0.3-30MUM did
      not enhance inhibiting effect of (+/-)-baclofen on depolarization-induced
      exocytotic release of [(3)H]GABA. Rac-BHFF (0.3-30MUM) caused dose-dependent
      depolarization of the plasma membrane and dissipation of the proton gradient of
      synaptic vesicles in synaptosomes that was shown in the absence/presence of GABAB
      receptor antagonist saclofen using fluorescent dyes rhodamine 6G and acridine
      orange, respectively, and so, the above effects of rac-BHFF were not associated
      with the modulation of presynaptic GABAB receptors. Therefore, drug development
      strategy of positive allosteric modulation of GABAB receptors is to eliminate the
      above side effects of rac-BHFF in presynapse, and vice versa, these new
      properties of rac-BHFF may be exploited appropriately. 

PMID- 26197224
TI  - Neuroprotective effect of astaxanthin against glutamate-induced cytotoxicity in
      HT22 cells: Involvement of the Akt/GSK-3beta pathway.
AB  - Oxidative stress (OS) mediated the pathogenesis of Alzheimer's disease (AD).
      Astaxanthin (ATX) has been reported to exert antioxidant activities as well as
      neuroprotective effects in vivo and in vitro. But it is still unknown whether the
      Akt/glycogen synthase kinase-3beta (GSK-3beta) signaling mediated the
      neuroprotective effect of ATX in HT22 cells. Flow cytometric analysis was used to
      evaluate reactive oxygen species (ROS) generation. Caspase and PARP activity was
      measured. The expressions of heme oxygenase-1 (HO-1), nuclear factor-E2-related
      factor 2 (Nrf2), Bcl-2, Bax, apoptosis-inducing factor (AIF), cytochrome-c (Cyto
      c), p-Akt and p-GSK-3beta were evaluated to elucidate the underlying mechanism.
      Our results showed that ATX significantly attenuated glutamate-induced cell
      viability loss and lactate dehydrogenase (LDH) release, decreased the expression
      of caspase-3/8/9 activity and cleaved PARP, and suppressed the intracellular
      accumulation of ROS in HT22 cells after exposure to glutamate. ATX also increased
      the mitochondrial expression of AIF, Cyto-c as well as Bax while decreased Bcl-2.
      Moreover, ATX also induced the HO-1 expression in a dose and time-dependent
      manner, increased the antioxidant-responsive element (ARE) activity and nuclear
      Nrf2 expression. Furthermore, treatment with ATX restored the p-Akt and p-GSK
      3beta (Ser9) as well as HO-1 expression reduced by glutamate. This protective
      effect was partially blocked by the inhibitors lithium chloride treatment in
      HT22, indicating the involvement of Akt/GSK-3beta inactivation during the
      neuroprotective effect of ATX. Our results provide the first evidence that ATX
      can protect glutamate-induced cytotoxicity in HT22 via attenuating caspase
      activation and mitochondrial dysfunction and modulating the Akt/GSK-3beta
      signaling, indicating ATX may be useful for the treatment of neurodegenerative
      disorders such as AD. 

PMID- 26197225
TI  - Oxidative stress caused by ozone exposure induces beta-amyloid 1-42
      overproduction and mitochondrial accumulation by activating the amyloidogenic
      pathway.
AB  - Oxidative stress is a major risk factor for Alzheimer's disease (AD) that has
      been suggested to be the trigger of AD pathology. However, whether oxidative
      damage precedes and contributes directly to the intracellular accumulation of
      beta amyloid 1-42 (betaA42) peptide remains a matter of debate. Chronic exposure
      to low doses of ozone similar to the levels during a day of high pollution in
      Mexico City causes a state of oxidative stress that elicits progressive
      neurodegeneration in the hippocampi of rats. Several reports have demonstrated
      that the mitochondria are among the first organelles to be affected by oxidative
      stress and betaA42 toxicity and act as sites of the accumulation of betaA42,
      which affects energy metabolism. However, the mechanisms related to the
      neurodegeneration process and organelle damage that occur in conditions of
      chronic exposure to low doses of ozone have not been demonstrated. To analyze the
      effect of chronic ozone chronic exposure on changes in the production and
      accumulation of the betaA42 and betaA40 peptides in the mitochondria of
      hippocampal neurons of rats exposed to ozone, we examined the mitochondrial
      expression levels of Presenilins 1 and 2 and ADAM10 to detect changes related to
      the oxidative stress caused by low doses of ozone (0.25ppm). The results revealed
      significant accumulations of betaA42 peptide in the mitochondrial fractions on
      days 60 and 90 of ozone exposure along with reductions in beta amyloid 1-40
      accumulation, significant overexpressions of Pres2 and significant reductions in
      ADAM10 expression. Beta amyloid immunodetection revealed that there were some
      intracellular deposits of betaA42 and that betaA42 and the mitochondrial markers
      OPA1 and COX1 colocalized. These results indicate that the time of exposure to
      ozone and the accumulation of betaA42 in the mitochondria of the hippocampal
      cells of rats were correlated. Our results suggest that the accumulation of the
      betaA42 peptide may promote mitochondrial dysfunction due to its accumulation and
      overproduction. 

PMID- 26197226
TI  - Single-dose intravenous administration of antiepileptic drugs induces rapid and
      reversible remodeling in the brain: Evidence from a voxel-based morphometry
      evaluation of valproate and levetiracetam in rhesus monkeys.
AB  - OBJECTIVE: Effects of the long-term use of antiepileptic drugs (AEDs) on the
      brains of patients with epilepsy have been previously reported. The aim of this
      study was to determine the rapid brain structure remodeling induced by single
      dose intravenous AED administration that rules out the potential effects of
      epilepsy. METHODS: Ten rhesus monkeys were randomly divided into two groups and
      were intravenously administered a single dose of valproic acid (VPA) or
      levetiracetam (LEV) at treatment dosages. Magnetic resonance imaging (MRI) data
      were recorded from every subject prior to AED administration and at 2h and 1 week
      after administration. Using optimized voxel-based morphometry (VBM) analysis, we
      measured changes in regional gray matter volume (GMV) and white matter volume
      (WMV) in each group over time following medication and directly compared the
      differences between the two groups. RESULTS: Both AEDs induced brain volume
      alterations at 2h after their administration, but these changes had reverted at 1
      week. The VPA group exhibited increased GMV in the right geniculate nucleus and
      the right pulvinar, whereas the LEV group exhibited WMV reductions in the right
      pulvinar, the right parietal lobe and the right occipital lobe. Directly compared
      with the LEV group, the VPA group exhibited a temporally constant GMV increase in
      the bilateral temporal cortex and a WMV reduction in the left pedunculus cerebri.
      CONCLUSIONS: Single-dose intravenous administration of a level of VPA or LEV that
      mimics clinical use is associated with rapid and reversible VBM-detected GMV or
      WMV alterations in rhesus monkeys. This finding may provide new insights into the
      understanding of AED-induced brain structure remodeling and may contribute to our
      understanding of the brain-level mechanisms and targets of AED action.

PMID- 26197227
TI  - Correction: Non-Cationic Proteins Are Associated with HIV Neutralizing Activity
      in Genital Secretions of Female Sex Workers.

PMID- 26197228
TI  - Comprehensive Synthesis of Monohydroxy-Cucurbit[n]urils (n = 5, 6, 7, 8): High
      Purity and High Conversions.
AB  - We describe a photochemical method to introduce a single alcohol function
      directly on cucurbit[n]urils (n = 5, 6, 7, 8) with conversions of the order 95
      100% using hydrogen peroxide and UV light. The reaction was easily scaled up to 1
      g for CB[6] and CB[7]. Spin trapping of cucurbituril radicals combined with MS
      experiments allowed us to get insights about the reaction mechanism and
      characterize CB[5], CB[6], CB[7], and CB[8] monofunctional compounds. Experiments
      involving (18)O isotopically labeled water indicated that the mechanism was
      complex and showed signs of both radical and ionic intermediates. DFT
      calculations allowed estimating the Bond Dissociation Energies (BDEs) of each
      hydrogen atom type in the CB series, providing an explanation of the higher
      reactivity of the "equatorial" C-H position of CB[n] compounds. These results
      also showed that, for CB[8], direct functionalization on the cucurbituril
      skeleton is more difficult because one of the methylene hydrogen atoms (Hb) has
      its BDE lowering within the series and coming close to that of Hc, thus opening
      the way to other types of free radicals generated on the CB[8] skeleton leading
      to several side products. Yet CB[5]-(OH)1 and CB[8]-(OH)1, the first CB[8]
      derivative, were obtained in excellent yields thanks to the soft method presented
      here. 

PMID- 26197229
TI  - Prevalence and Predictors of Gastrostomy Tube and Tracheostomy Placement in
      Anoxic/Hypoxic Ischemic Encephalopathic Survivors of In-Hospital Cardiopulmonary
      Resuscitation in the United States.
AB  - INTRODUCTION: Current prevalence estimates of gastrostomy tube (GT)/tracheostomy
      placement in hospitalized patients with anoxic/hypoxic ischemic encephalopathic
      injury (AHIE) post cardiopulmonary resuscitation (CPR) are unknown. We sought, to
      estimate the prevalence of AHIE in hospitalized patients who had CPR and to
      identify patient/hospital level factors that predict the performance of
      GT/tracheostomy in those with AHIE. METHODS: We performed a retrospective
      analysis of the Nationwide Inpatient Sample (years 2004-2010). All patients who
      developed AHIE following CPR were included. In this cohort the odds of having GT
      and tracheostomy was computed by multivariable logistic regression analysis.
      Patient and hospital level factors were the independent variables. RESULTS:
      During the study period, a total of 686,578 CPR events occurred in hospitalized
      patients. Of these, 94,336 (13.7%) patients developed AHIE. In this AHIE cohort,
      6.8% received GT and 8.3% tracheostomy. When compared to the 40-49 yrs age group,
      those aged >70 yrs were associated with lower odds for GT (OR = 0.65, 95% CI:0.53
      0.80, p<0.0001). Those aged <18 years & those >60 years were associated with
      lower odds for having tracheostomy when compared to the 40-49 years group
      (p<0.0001). Each one unit increase in co-morbid burden was associated with higher
      odds for having GT (OR = 1.23,p<0.0001) or tracheostomy (OR = 1.17, p<0.0001).
      Blacks, Hispanics, Asians/Pacific Islanders, and other races were associated with
      higher odds for having GT or tracheostomy when compared to whites (p<0.05).
      Hospitals located in northeastern regions were associated with higher odds for
      performing GT (OR = 1.48, p<0.0001) or tracheostomy (OR = 1.63, p<0.0001) when
      compared to those in Western regions. Teaching hospitals (TH) were associated
      with higher odds for performing tracheostomy when compared to non-TH (OR = 1.36,
      1.20-1.54, p<0.0001). CONCLUSIONS: AHIE injury occurs in a significant number of
      in-hospital arrests requiring CPR. Certain predictors of GT/ Tracheostomy
      placement are identified. Patients in teaching hospitals were more likely to
      receive tracheostomy than their counterparts.

PMID- 26197230
TI  - Progress in Understanding Algal Bloom-Mediated Fish Kills: The Role of Superoxide
      Radicals, Phycotoxins and Fatty Acids.
AB  - Quantification of the role of reactive oxygen species, phycotoxins and fatty
      acids in fish toxicity by harmful marine microalgae remains inconclusive. An in
      vitro fish gill (from rainbow trout Oncorhynchus mykiss) assay was used to
      simultaneously assess the effect in superoxide dismutase, catalase and lactate
      dehydrogenase enzymatic activities caused by seven species of ichthyotoxic
      microalgae (Chattonella marina, Fibrocapsa japonica, Heterosigma akashiwo,
      Karenia mikimotoi, Alexandrium catenella, Karlodinium veneficum, Prymnesium
      parvum). Quantification of superoxide production by these algae was also
      performed. The effect of purified phycotoxins and crude extracts was compared,
      and the effect of fatty acids is discussed. The raphidophyte Chattonella was the
      most ichthyotoxic (gill cell viability down to 35%) and also the major producer
      of superoxide radicals (14 pmol cell-1 hr-1) especially after cell lysis. The
      raphidophyte Heterosigma and dinoflagellate Alexandrium were the least toxic and
      had low superoxide production, except when A. catenella was lysed (5.6 pmol cell
      1 hr-1). Catalase showed no changes in activity in all the treatments. Superoxide
      dismutase (SOD) and lactate dehydrogenase exhibited significant activity
      increases of <=23% and 51.2% TCC (total cellular content), respectively, after
      exposure to C. marina, but SOD showed insignificant changes with remaining algal
      species. A strong relationship between gill cell viability and superoxide
      production or superoxide dismutase was not observed. Purified brevetoxins PbTx-2
      and -3 (from Karenia brevis, LC50 of 22.1 versus 35.2 MUg mL-1) and karlotoxin
      KmTx-2 (from Karlodinium; LC50 = 380 ng mL-1) could almost entirely account for
      the fish killing activity by those two dinoflagellates. However, the paralytic
      shellfish toxins (PST) GTX1&4, C1&C2, and STX did not account for Alexandrium
      ichthyotoxicity. Only aqueous extracts of Alexandrium were cytotoxic (<=65%
      decrease of viability), whereas crude methanol and acetone extracts of
      Chattonella, Fibrocapsa, Heterosigma, Karlodinium and Prymnesium decreased cell
      viability down to 0%. These and our previous findings involving the role of fatty
      acids confirm that superoxide radicals are only partially involved in
      ichthyotoxicity and point to a highly variable contribution by other compounds
      such as lipid peroxidation products (e.g. aldehydes).

PMID- 26197231
TI  - A Mathematical Model of Quorum Sensing Induced Biofilm Detachment.
AB  - BACKGROUND: Cell dispersal (or detachment) is part of the developmental cycle of
      microbial biofilms. It can be externally or internally induced, and manifests
      itself in discrete sloughing events, whereby many cells disperse in an instance,
      or in continuous slower dispersal of single cells. One suggested trigger of cell
      dispersal is quorum sensing, a cell-cell communication mechanism used to
      coordinate gene expression and behavior in groups based on population densities.
      METHOD: To better understand the interplay of colony growth and cell dispersal,
      we develop a dynamic, spatially extended mathematical model that includes biofilm
      growth, production of quorum sensing molecules, cell dispersal triggered by
      quorum sensing molecules, and re-attachment of cells. This is a highly nonlinear
      system of diffusion-reaction equations that we study in computer simulations.
      RESULTS: Our results show that quorum sensing induced cell dispersal can be an
      efficient mechanism for bacteria to control the size of a biofilm colony, and at
      the same time enhance its downstream colonization potential. In fact we find that
      over the lifetime of a biofilm colony the majority of cells produced are lost
      into the aqueous phase, supporting the notion of biofilms as cell nurseries. We
      find that a single quorum sensing based mechanism can explain both, discrete
      dispersal events and continuous shedding of cells from a colony. Moreover, quorum
      sensing induced cell dispersal affects the structure and architecture of the
      biofilm, for example it might lead to the formation of hollow inner regions in a
      biofilm colony.

PMID- 26197232
TI  - Nature of CTAB/Water/Chloroform Reverse Micelles at Above- and Subzero
      Temperatures Studied by NMR and Molecular Dynamics Simulations.
AB  - The nature and stability of cetyltrimethylammonium bromide (CTAB) reverse
      micelles in chloroform formed above the critical micellar concentration at above-
      and subzero temperatures were examined by NMR and molecular dynamics simulations.
      The experiments showed that the supercooled micellar water pool becomes unstable
      upon cooling to relatively high temperatures (253 K), and smaller micelles are
      formed. Upon freezing at lower temperatures (233 K), micelles become completely
      frozen and remain intact in the solution. With an average hydrodynamic radius of
      approximately 1.3 nm, we estimate that the water pool contains approximately 50
      water molecules, which is well below the onset of ice crystal formation. To
      support the experimental results, molecular dynamics simulations were used to
      model the structure of CTAB/water/chloroform reverse micelles of different sizes.
      The MD simulations show that the reverse micelles contain a water pool with
      bromide anions residing on its surface and their shape is nonspherical,
      especially in the case of larger water pools. Upon fast freezing, the mobility of
      the water molecules is suppressed, and the pool becomes more spherical. 

PMID- 26197233
TI  - Bartonella spp. and Coxiella burnetii Associated with Community-Acquired, Culture
      Negative Endocarditis, Brazil.
AB  - We evaluated culture-negative, community-acquired endocarditis by using indirect
      immunofluorescent assays and molecular analyses for Bartonella spp. and Coxiella
      burnetii and found a prevalence of 19.6% and 7.8%, respectively. Our findings
      reinforce the need to study these organisms in patients with culture-negative,
      community-acquired endocarditis, especially B. henselae in cat owners. 

PMID- 26197234
TI  - BMP7-Based Functionalized Self-Assembling Peptides for Nucleus Pulposus Tissue
      Engineering.
AB  - Nucleus pulposus (NP) tissue engineering has been demonstrated to be a feasible
      therapeutic strategy for intervertebral disc regeneration. In this study, we
      constructed a novel injectable biomaterial by conjugating three different short
      peptides of BMP7 to the C-terminus of the self-assembling peptide RADA16-I, and
      we then mixed each of these conjugates with RADA16-I at equal volumes to obtain
      the novel functionalized peptides RAD-SNV, RAD-KPS, and RAD-KAI. The
      bioactivities of these functionalized peptides for human degenerated NP cells
      (hdNPCs) were evaluated in vitro, and the most ideal scaffold was chosen for
      assessment of its in vivo degradation and the tissue reactions to it. All of the
      functionalized peptides self-assembled to form hydrogel scaffolds with a
      nanofibrous structure under physiological conditions. Compared with the RADA16-I
      and RAD-KAI scaffolds, the RAD-SNV and RAD-KPS scaffolds possessed better
      bioactivities for hdNPCs, which were characterized by their enhanced
      proliferation, migration, and ECM (collagen II, aggrecan, and sox-9) secretion.
      RAD-KPS was chosen over RAD-SNV as the most ideal scaffold material due to the
      cells' higher rate of expression of aggrecan both at the gene and protein level
      after 28 days of coculture. Moreover, in vivo analysis demonstrated that
      subcutaneously injected RAD-KPS degraded in vivo without invoking intense
      inflammation. Therefore, RAD-KPS is an ideal candidate scaffold for NP tissue
      engineering and holds great potential for NP regeneration. 

PMID- 26197235
TI  - Foam Cell Formation In Vivo Converts Macrophages to a Pro-Fibrotic Phenotype.
AB  - Formation of foam cell macrophages, which sequester extracellular modified
      lipids, is a key event in atherosclerosis. How lipid loading affects macrophage
      phenotype is controversial, with evidence suggesting either pro- or anti
      inflammatory consequences. To investigate this further, we compared the
      transcriptomes of foamy and non-foamy macrophages that accumulate in the
      subcutaneous granulomas of fed-fat ApoE null mice and normal chow fed wild-type
      mice in vivo. Consistent with previous studies, LXR/RXR pathway genes were
      significantly over-represented among the genes up-regulated in foam cell
      macrophages. Unexpectedly, the hepatic fibrosis pathway, associated with platelet
      derived growth factor and transforming growth factor-beta action, was also over
      represented. Several collagen polypeptides and proteoglycan core proteins as well
      as connective tissue growth factor and fibrosis-related FOS and JUN transcription
      factors were up-regulated in foam cell macrophages. Increased expression of
      several of these genes was confirmed at the protein level in foam cell
      macrophages from subcutaneous granulomas and in atherosclerotic plaques.
      Moreover, phosphorylation and nuclear translocation of SMAD2, which is downstream
      of several transforming growth factor-beta family members, was also detected in
      foam cell macrophages. We conclude that foam cell formation in vivo leads to a
      pro-fibrotic macrophage phenotype, which could contribute to plaque stability,
      especially in early lesions that have few vascular smooth muscle cells. 

PMID- 26197236
TI  - Efficacy of Visual Surveys for White-Nose Syndrome at Bat Hibernacula.
AB  - White-Nose Syndrome (WNS) is an epizootic disease in hibernating bats caused by
      the fungus Pseudogymnoascus destructans. Surveillance for P. destructans at bat
      hibernacula consists primarily of visual surveys of bats, collection of
      potentially infected bats, and submission of these bats for laboratory testing.
      Cryptic infections (bats that are infected but display no visual signs of fungus)
      could lead to the mischaracterization of the infection status of a site and the
      inadvertent spread of P. destructans. We determined the efficacy of visual
      detection of P. destructans by examining visual signs and molecular detection of
      P. destructans on 928 bats of six species at 27 sites during surveys conducted
      from January through March in 2012-2014 in the southeastern USA on the leading
      edge of the disease invasion. Cryptic infections were widespread with 77% of bats
      that tested positive by qPCR showing no visible signs of infection. The
      probability of exhibiting visual signs of infection increased with sampling date
      and pathogen load, the latter of which was substantially higher in three species
      (Myotis lucifugus, M. septentrionalis, and Perimyotis subflavus). In addition, M.
      lucifugus was more likely to show visual signs of infection than other species
      given the same pathogen load. Nearly all infections were cryptic in three species
      (Eptesicus fuscus, M. grisescens, and M. sodalis), which had much lower fungal
      loads. The presence of M. lucifugus or M. septentrionalis at a site increased the
      probability that P. destructans was visually detected on bats. Our results
      suggest that cryptic infections of P. destructans are common in all bat species,
      and visible infections rarely occur in some species. However, due to very high
      infection prevalence and loads in some species, we estimate that visual surveys
      examining at least 17 individuals of M. lucifugus and M. septentrionalis, or 29
      individuals of P. subflavus are still effective to determine whether a site has
      bats infected with P. destructans. In addition, because the probability of
      visually detecting the fungus was higher later in winter, surveys should be done
      as close to the end of the hibernation period as possible.

PMID- 26197237
TI  - Downregulation of SKA1 Gene Expression Inhibits Cell Growth in Human Bladder
      Cancer.
AB  - Spindle and kinetochore-associated protein 1 (SKA1), a component of microtubule
      binding complex of kinetochore, is essential for proper chromosome segregation.
      Recently, SKA1 has been shown to be involved in malignant progression of several
      human cancers. However, its role in bladder cancer is still unknown. To evaluate
      the function of SKA1 in bladder cancer cells, the authors employed an RNA
      interference lentivirus system to deplete its expression in both BT5637 and T-24
      bladder cancer cells. The cell proliferation was significantly decreased in both
      cell lines after SKA1 knockdown. Moreover, the colony formation capacity was
      impaired by SKA1 silencing. Flow cytometry analysis showed that depletion of SKA1
      led to cell cycle arrest at S phase. Furthermore, knockdown of SKA1 in T-24 cells
      obviously downregulated the expressions of CDK4 and Cyclin D1, and alleviated the
      activations of ERK2 and AKT, conducive to cell growth inhibition. These findings
      suggested that knockdown of SKA1 could potently suppress bladder cancer cell
      proliferation in vitro and lentivirus-mediated silencing of SKA1 might serve as a
      novel strategy for gene therapy of bladder cancer. 

PMID- 26197238
TI  - The histiocytosis Erdheim-Chester disease is an inflammatory myeloid neoplasm.
AB  - Erdheim-Chester disease (ECD) is a rare, non-Langerhans histiocytosis,
      characterized by the infiltration of tissues by foamy CD68(+)CD1a(-) histiocytes.
      (99)Technetium bone scintigraphy revealing almost constant tracer uptake by the
      long bones is highly suggestive of ECD, and a 'hairy kidney' appearance on
      abdominal computed tomography scan is observed in about half of all ECD cases.
      CNS involvement is a strong prognostic factor and independent predictor of death.
      IFN-alpha seems to be the best initial treatment for ECD. More than half of all
      ECD patients carry the BRAF(V600E) mutation. More than 30 patients worldwide
      harboring this mutation and displaying multisystemic, refractory ECD have been
      treated with vemurafenib, a BRAF inhibitor, which has proven highly beneficial.
      Other recurrent mutations of the MAPK and PIK3 pathways (NRAS, PIK3CA) have
      recently been described. These mutations should lead to a new classification of
      histiocytic disorders such that Langerhans cell histiocytosis and ECD are
      classified as inflammatory myeloid neoplasms. 

PMID- 26197241
TI  - The scrutiny of identifying community-acquired pneumonia episodes quantified bias
      in absolute effect estimation in a population-based pneumococcal vaccination
      trial.
AB  - OBJECTIVES: To determine the accurateness of detecting community-acquired
      pneumonia (CAP) in the Community-Acquired Pneumonia immunization Trial in Adults
      (CAPiTA), a community-based, double-blind, randomized placebo-controlled trial in
      which the needed to treat (NNT) for prevention of vaccine-type pneumococcal CAP
      was 1,007 [95% confidence interval (CI): 613, 2,646]. STUDY DESIGN AND SETTING:
      Study participants developing pneumonia were identified in 58 participating
      hospitals by research nurses (RNs) using local-adapted protocols. In addition,
      general practitioner (GP) records were screened for hospital referrals for
      suspected pneumonia. Two independent reviewers determined reasons for not
      identifying pneumonia episodes, and the NNT adjusted for missed episodes was
      estimated. RESULTS: Of 2,183 hospital referrals with suspected pneumonia detected
      in GP records, 232 (11%) were admitted outside established screening routes and
      102 (5%) were not suspected of pneumonia on admission. Of the remaining 1,849
      episodes, 1,374 (63% of all episodes and 74% of identifiable episodes) were
      identified by RNs. Several causes of missing episodes were identified. After
      adjustment for missed episodes, the NNT reduced to 634 (95% CI: 386, 1,675).
      CONCLUSION: With the screening procedure, 63% of suspected pneumonia episodes
      were identified, and the estimated NNT reduced from 1,007 to 634. Root cause
      analysis of unidentified episodes provides guidance for improving pneumonia
      detection in future trials.

PMID- 26197240
TI  - The Mkk2 MAPKK Regulates Cell Wall Biogenesis in Cooperation with the Cek1
      Pathway in Candida albicans.
AB  - The cell wall integrity pathway (CWI) plays an important role in the biogenesis
      of the cell wall in Candida albicans and other fungi. In the present work, the C.
      albicans MKK2 gene that encodes the putative MAPKK of this pathway was deleted in
      different backgrounds and the phenotypes of the resultant mutants were
      characterised. We show here that Mkk2 mediates the phosphorylation of the Mkc1
      MAPK in response to cell wall assembly interfering agents such as zymolyase or
      tunicamycin and also to oxidative stress. Remarkably, mkk2 and mkc1 mutants
      display related but distinguishable- cell wall associated phenotypes and differ
      in the pattern of MAPK phosphorylation under different stress conditions. mkk2
      and mkc1 mutants display an altered expression of GSC1, CEK1 and CRH11 genes at
      different temperatures. Combined deletion of MKK2 with HST7 supports a
      cooperative role for the Cek1-mediated and CWI pathways in regulating cell wall
      architecture under vegetative growth. However, and in contrast to Mkc1, Mkk2 does
      not seem to play a role in the virulence of C. albicans in the mouse systemic
      model or the Galleria mellonella model of infection.

PMID- 26197239
TI  - Associations of the Inflammatory Marker YKL-40 with Measures of Obesity and
      Dyslipidaemia in Individuals at High Risk of Type 2 Diabetes.
AB  - INTRODUCTION: Circulating levels of the inflammatory marker YKL-40 are elevated
      in cardiovascular disease and obesity-related type 2 diabetes (T2D), and serum
      YKL-40 levels are related to elements of dyslipidaemia. OBJECTIVE: We aimed to
      investigate the associations between serum YKL-40 and obesity-related traits in a
      Danish sample of non-diabetic relatives to T2D patients and, furthermore, to
      estimate the heritability of YKL-40. RESEARCH DESIGN AND METHODS: 324 non
      diabetic individuals with family relation to a T2D patient were included in the
      study. The participants underwent oral- and intravenous glucose tolerance tests
      for estimation of glucose tolerance and surrogate measures of insulin
      sensitivity. Anthropometric measures were retrieved and biochemical measures of
      the plasma lipid profile and serum YKL-40 levels were obtained. Association
      analyses between serum YKL-40 and obesity-related traits and estimates of the
      narrow sense heritability of YKL-40 were based on a polygenic variance component
      model. RESULTS: Fasting serum levels of YKL-40 were positively associated with
      waist-hip-ratio (p<0.001) and fasting plasma triglyceride levels (p<0.001). None
      of the insulin sensitivity indexes were significantly associated with YKL-40.
      According to the AE model, the familiality-estimate h2 of YKL-40 was 0.45 (SE
      0.13). When the ACE-model was applied, the heritability-estimate h2 of YKL-40 did
      not reach statistical significance. CONCLUSIONS: Our results suggest a role of
      serum YKL-40 in obesity-related low grade inflammation, but do not indicate that
      YKL-40 is directly involved in the development of T2D.

PMID- 26197242
TI  - Transmission Dynamics and Final Epidemic Size of Ebola Virus Disease Outbreaks
      with Varying Interventions.
AB  - The 2014 Ebola Virus Disease (EVD) outbreak in West Africa was the largest and
      longest ever reported since the first identification of this disease. We propose
      a compartmental model for EVD dynamics, including virus transmission in the
      community, at hospitals, and at funerals. Using time-dependent parameters, we
      incorporate the increasing intensity of intervention efforts. Fitting the system
      to the early phase of the 2014 West Africa Ebola outbreak, we estimate the basic
      reproduction number as 1.44. We derive a final size relation which allows us to
      forecast the total number of cases during the outbreak when effective
      interventions are in place. Our model predictions show that, as long as cases are
      reported in any country, intervention strategies cannot be dismissed. Since the
      main driver in the current slowdown of the epidemic is not the depletion of
      susceptibles, future waves of infection might be possible, if control measures or
      population behavior are relaxed. 

PMID- 26197243
TI  - LINE-1 methylation levels, a biomarker of weight loss in obese subjects, are
      influenced by dietary antioxidant capacity.
AB  - OBJECTIVES: Epigenetic markers, and in particular DNA methylation, have come to
      the fore as new tools in the personalization of the treatment of obesity and its
      comorbidities. The objectives of the current investigation were to identify
      epigenetic biomarkers that might be predictive of response to a weight-loss
      intervention, and to better understand the influence of certain nutrients
      (particularly antioxidants) on the epigenome. METHODS: Global DNA (LINE-1)
      methylation levels were assessed in peripheral blood mononuclear cells (PBMCs)
      from 96 obese volunteers of the Metabolic Syndrome Reduction in Navarra study,
      using a methylation-sensitive high resolution melting approach after bisulfite
      modification. RESULTS: Baseline LINE-1 DNA methylation levels were significantly
      higher (5.41%) in high responders (>8% of weight loss) as compared to low
      responders (<8%) to the energy-restricted treatment. Indeed, a LINE-1 methylation
      higher than 84.15% may be predictive of a high response to the hypocaloric diet.
      Statistically significant correlations were found between LINE-1 baseline DNA
      methylation levels and the response to the treatment involving total fat mass and
      body weight. Furthermore, LINE-1 baseline methylation levels positively
      correlated with baseline dietary total antioxidant capacity (TAC). DISCUSSION:
      LINE-1 methylation levels in PBMCs might be used to predict response to a dietary
      weight-loss intervention, and seem to be related to the dietary TAC. TRIAL
      REGISTRATION: www.clinicaltrials.gov : NCT01087086.

PMID- 26197244
TI  - An in vivo evaluation of acute toxicity of cobalt ferrite (CoFe2O4) nanoparticles
      in larval-embryo Zebrafish (Danio rerio).
AB  - The broad spectrum applications of CoFe2O4 NPs have attracted much interest in
      medicine, environment and industry, resulting in exceedingly higher exposures to
      humans and environmental systems in succeeding days. Their health effects and
      potential biological impacts need to be determined for risk assessment. Zebrafish
      (Danio rerio) embryos were exposed to environmentally relevant doses of nano
      CoFe2O4 (mean diameter of 40nm) with a concentration range of 10-500MUM for 96h.
      Acute toxic end points were evaluated by survival rate, malformation, hatching
      delay, heart dysfunction and tail flexure of larvae. Dose and time dependent
      developmental toxicity with severe cardiac edema, down regulation of metabolism,
      hatching delay and tail/spinal cord flexure and apoptosis was observed. The
      biochemical changes were evaluated by ROS, Catalase (CAT), Lipid peroxidation
      (LPO), Acid phophatase (AP) and Glutatione s- transferase (GST). An Agglomeration
      of NPs and dissolution of ions induces severe mechanical damage to membranes and
      oxidative stress. Severe apoptosis of cells in the head, heart and tail region
      with inhibition of catalase confirms ROS induced acute toxicity with increasing
      concentration. Increased activity of GST and AP at lower concentrations of
      CoFe2O4 NPs demonstrates the severe oxidative stress. Circular dichroism (CD)
      spectra indicated the weak interactions of NPs with BSA and slight changes in
      alpha-helix structure. In addition, CoFe2O4 NPs at lower concentrations do not
      show any considerable interference with assay components and analytical
      instruments. The results are possible elucidation of pathways of toxicity induced
      by these particles, as well as contributing in defining the protocols for risk
      assessment of these nanoparticles. 

PMID- 26197245
TI  - Altered lung function at mid-adulthood in mice following neonatal exposure to
      hyperoxia.
AB  - Infants born very preterm are usually exposed to high oxygen concentrations but
      this may impair lung function in survivors in later life. However, the precise
      changes involved are poorly understood. We determined how neonatal hyperoxia
      alters lung function at mid-adulthood in mice. Neonatal C57BL/6J mice inhaled 65%
      oxygen (HE group) from birth for 7 days. They then breathed room air until 11
      months of age (P11mo); these mice experienced growth restriction. Controls
      breathed only room air. To exclude the effects of growth restriction, a group of
      dams was rotated between hyperoxia and normoxia during the exposure period (HE+DR
      group). Lung function was measured at P11mo. HE mice had increased inspiratory
      capacity, work of breathing and tissue damping. HE+DR mice had further increases
      in inspiratory capacity and work of breathing, and reduced FEV100/FVC. Total lung
      capacity was increased in HE+DR males. HE males had elevated responses to
      methacholine. Neonatal hyperoxia alters lung function at mid-adulthood,
      especially in males. 

PMID- 26197246
TI  - Modeling the pharyngeal pressure during adult nasal high flow therapy.
AB  - Subjects receiving nasal high flow (NHF) via wide-bore nasal cannula may
      experience different levels of positive pressure depending on the individual
      response to NHF. In this study, airflow in the nasal airway during NHF-assisted
      breathing is simulated and nasopharyngeal airway pressure numerically computed,
      to determine whether the relationship between NHF and pressure can be described
      by a simple equation. Two geometric models are used for analysis. In the first,
      3D airway geometry is reconstructed from computed tomography images of an adult
      nasal airway. For the second, a simplified geometric model is derived that has
      the same cross-sectional area as the complex model, but is more readily amenable
      to analysis. Peak airway pressure is correlated as a function of nasal valve
      area, nostril area and cannula flow rate, for NHF rates of 20, 40 and 60 L/min.
      Results show that airway pressure is related by a power law to NHF rate, valve
      area, and nostril area.

PMID- 26197247
TI  - Lying (or Maybe Just Misleading) With (or Without) Statistics.

PMID- 26197249
TI  - Using What's Learned in the Game for Use in Real Life.
AB  - A player can learn many things from playing a game for health. Some of these
      learnings were deliberately designed for the player to use in his or her real
      life, outside of any game. The effective ways to enable players to generalize
      what they learn in the game to their real lives (and thereby benefit from playing
      the game) are not clear. We have convened a group of expert health game designers
      and researchers to discuss this important issue. 

PMID- 26197250
TI  - Fighting Dementia with Brain Health Assessment.

PMID- 26197251
TI  - A Comparison of Energy Expenditure During "Wii Boxing" Versus Heavy Bag Boxing in
      Young Adults.
AB  - Traditional computer videogames are sedentary, whereas new computer videogames,
      such as the Nintendo((r)) (Redmond, WA) "WiiTM Sports" games, allow users to
      physically interact while playing the sport. Energy expenditure (EE), heart rate
      (HR), and rating of perceived exertion (RPE) during heavy bag boxing versus the
      Nintendo "Wii Boxing" game were compared. Fifteen males and 14 females (mean age,
      25.6 years; height, 171.3 cm; weight, 71.8 kg) randomly selected (by a coin toss)
      heavy bag boxing or "Wii Boxing" for their first test session and completed the
      other protocol at their second session at least 2 days later. Each session lasted
      for a total duration of 30 minutes and consisted of 10 3-minute exercise bouts
      with measurements of HR, RPE, and EE obtained from indirect calorimetry. A paired
      samples t test was used to analyze the results. Significant differences were
      found for HR (bag, 156 beats per minute; Wii, 138 beats per minute; P=0.001) and
      RPE (bag, 13.8; Wii, 11.4; P=0.0001) but not for EE (bag, 8.0 kcal/minute; Wii,
      7.1 kcal/minute; bag, 241 total kcal; Wii, 213 total kcal; P=0.078). The results
      suggest that computer active videogames, such as the Nintendo Wii, have the
      potential to provide similar EE as their traditional forms of exercise and may be
      a sufficient replacement for traditional target HR zone activities, especially in
      less fit individuals. Further research is needed to compare EE for different "Wii
      Sports" games with those for their traditional forms of exercise. 

PMID- 26197252
TI  - Are "Wii" Exercising Correctly? Understanding How Exergames Can Be Used to
      Increase Knowledge of Exercise Behavior.
AB  - OBJECTIVE: Many studies have investigated how commercial exergames can be used to
      increase physical activity and energy expenditure, but relatively few have
      focused on understanding if these games can impact learning of exercise behavior.
      The objective of this research is to understand how features of mediated exercise
      technologies can impact learning of exercise behavior. SUBJECTS AND METHODS: One
      hundred thirty college students (mean age, 20.56 years old) participated in a
      between-subjects experiment where they spent approximately 10 minutes exercising
      with either the "Biggest Loser" exergame (for the Nintendo((r)) [Redmond, WA]
      WiiTM console) or the Biggest Loser Workout Vol. 2 DVD. Then, participants filled
      out a questionnaire with items pertaining to interactivity, trainer liking, self
      efficacy, and learning. RESULTS: Analysis of covariance tests and meditational
      analyses were used to answer the questions of interest. Results indicated that
      participants who interacted with an exergame experienced greater interactivity
      and learning from playing the game than working out with the nearly identical
      exercise DVD. Furthermore, the relationship between playing an exergame and
      learning was mediated by interactivity. CONCLUSIONS: This study suggests that
      exergames may be more beneficial than similar mediated exercise companions in
      encouraging learning about exercise. Theoretical and practical implications as
      well as limitations and future research considerations are discussed.

PMID- 26197253
TI  - Effect of Pregame Training Tutorials on Player Performance in Kinect-Based Health
      Games.
AB  - OBJECTIVE: The objective of this study was to examine the influence of pregame
      tutorials on player performance in Kinect((r)) (Microsoft((r)), Redmond, WA)
      based health games and to determine whether the additional exertion caused by
      longer playtime introduced by the tutorial would influence in-game performance.
      MATERIALS AND METHODS: Thirty-two college-age test participants were randomly
      assigned to two groups: pregame training tutorial and pregame verbal
      instructions. The variable of interest was the degree to which players were able
      to accurately perform a series of static arm gestures in order to duplicate
      specific reference poses. Participants played a Kinect-based bird simulator game
      called "Burnie" that required the player to hold specific, static poses that
      correspond to physical therapy treatment actions. This study is a pilot conducted
      in advance of testing the game with its target audience of pediatric cerebral
      palsy patients. RESULTS: Analysis of variance did not detect a significant
      difference in pose accuracy between the tutorial and nontutorial groups. However,
      the tutorial group's pose accuracy was higher on average than that of the
      nontutorial group. CONCLUSIONS: Given the limited sample size in this study, it
      cannot be stated with certainty that greater pose accuracy will occur if a
      pregame tutorial level is administered. However, a trend was observed along most
      measures that the tutorial group achieved greater accuracy scores than the verbal
      instruction group. Further study with greater statistical power is strongly
      recommended.

PMID- 26197254
TI  - Wii, Myself, and Size: The Influence of Proteus Effect and Stereotype Threat on
      Overweight Children's Exercise Motivation and Behavior in Exergames.
AB  - OBJECTIVE: Exercise-based videogames, or exergames, provide a promising and novel
      way to improve exercise attitudes and behavior among overweight children. These
      digital interventions often allow for customizations of player characters and
      weave in narratives and goals. Theoretically, the presence of visual identity
      cues (e.g., avatars) and social category cues (e.g., stereotypes) within the
      virtual gaming environment are likely to motivate a player's exercise attitudes
      and behavior in various ways. This study examined the effects of both visual cues
      (via the Proteus effect) and social cues (via stereotype threat) on overweight
      children's exercise attitudes and game performance in a virtual running game.
      SUBJECTS AND METHODS: A 2 (avatar body size: Normal versus overweight)*2
      (stereotype threat: Present versus absent) factorial design experiment was
      conducted with 140 overweight children between 9 to 12 years of age. Dependent
      variables measured were participants' exercise attitudes, exercise motivation,
      exercise motivation with regard to the Nintendo((r)) (Kyoto, Japan) WiiTM, and
      their in-game performance. RESULTS: Multivariate analysis of covariance tests
      showed that overweight children assigned to avatars of normal body size scored
      significantly better on all four variables compared with those assigned to
      avatars of large body size, whereas overweight children assigned to a stereotype
      threat absent condition scored significantly better on three of the four
      variables compared with those assigned to a stereotype threat present condition.
      CONCLUSIONS: Using avatars with normal body size and not being subjected to
      stereotypical messages has the potential to increase the effectiveness of
      exergames among overweight children. Exergame developers should consider
      designing avatars that are slim and toned and set "weight neutral" goals and
      challenges. These may provide more motivation and yield greater attitudinal and
      behavioral changes among overweight children.

PMID- 26197255
TI  - Review of Games for Health: Proceedings of the 3(rd) European Conference on
      Gaming and Playful Interaction in Health Care.

PMID- 26197257
TI  - Neurophysiological sensitivity for impaired phonological processing in the acute
      stage of aphasia.
AB  - The present study aimed to investigate neurophysiological substrates of phoneme
      and word processing in 10 patients with acute aphasia (PWA). More specifically,
      phoneme discrimination was studied in a passive and active oddball task with
      respect to different phonemic contrasts, while lexical detection was investigated
      by presenting infrequent pseudowords among frequent words in a passive oddball
      task. Concerning phoneme discrimination, PWA in the acute stage had smaller MMN
      and P300 amplitudes than the norm group for voicing, whereas for place and manner
      they only demonstrated smaller P300 amplitudes. PWA showed a distinct pattern of
      impaired phonemic contrast sensitivity, with place displaying the largest
      amplitude and voicing the smallest. Concerning lexical detection, pseudowords
      elicited larger responses than words in both groups, but with a delay and larger
      P200 amplitude for pseudowords in PWA compared to the norm group. For clinical
      practice, passive tasks seem more suitable than active tasks in acute aphasia. 

PMID- 26197258
TI  - Speech preparation in adults with persistent developmental stuttering.
AB  - Motor efference copy conveys movement information to sensory areas before and
      during vocalization. We hypothesized speech preparation would modulate auditory
      processing, via motor efference copy, differently in men who stutter (MWS) vs.
      fluent adults. Participants (n=12/group) had EEG recorded during a cue-target
      paradigm with two conditions: speech which allowed for speech preparation, while
      a control condition did not. Acoustic stimuli probed auditory responsiveness
      between the cue and target. MWS had longer vocal reaction times (p<0.01) when the
      cue-target differed (10% of trials), suggesting a difficulty of rapidly updating
      their speech plans. Acoustic probes elicited a negative slow wave indexing motor
      efference copy that was smaller in MWS vs. fluent adults (p<0.03). Current
      density responses in MWS showed smaller left prefrontal responses and auditory
      responses that were delayed and correlated to stuttering rate. Taken together,
      the results provide insight into the cortical mechanisms underlying atypical
      speech planning and dysfluencies in MWS. 

PMID- 26197259
TI  - Developmental phonagnosia: Neural correlates and a behavioral marker.
AB  - A 20-year old female, AN, with no history of neurological events or detectable
      lesions, was markedly poorer than controls at identifying her most familiar
      celebrity voices. She was normal at face recognition and in discriminating which
      of two speakers uttered a particular sentence. She evidences normal fMRI
      sensitivity for human speech and non-speech sounds. AN, and two other
      phonagnosics, were unable to imagine the voices of highly familiar individuals. A
      region in the ventromedial prefrontal cortex (vmPFC) was differentially activated
      in controls when imagining familiar celebrity voices compared to imagining non
      voice sounds. AN evidenced no differential activation in this area, which has
      been termed a person identity semantic system. Rather than a deficit in the
      representation of voice-individuating cues, AN may be unable to associate those
      cues to the identity of a familiar person. In this respect, the deficit in
      developmental phonagnosia may bear a striking parallel to developmental
      prosopagnosia. 

PMID- 26197260
TI  - An educational intervention on drug interactions and contraceptive options for
      epilepsy patients: a pilot randomized controlled trial.
AB  - OBJECTIVE: This pilot study investigates whether an educational handout could
      increase short-term information retention about drug interactions between
      antiepileptic drugs (AEDs) and hormonal contraceptives among female epilepsy
      patients of reproductive age. STUDY DESIGN: This is a pilot randomized controlled
      trial of an educational intervention among reproductive-age women with epilepsy
      in an academic neurology clinic. Investigators measured knowledge before and
      after participants received either usual care or the educational handout. The 10
      question test assessed increased knowledge of which AEDs affected efficacy of
      certain hormonal contraceptives and was assessed by calculating the improvement
      in score between the pretest and posttest. The educational handout included the
      names of AEDs that have drug interactions with certain contraceptives and the
      efficacy of the contraceptives. RESULTS: A total of 42 epilepsy patients
      participated in this study. Fourteen participants were taking AEDs that are
      enzyme p450 inducers and 13 participants were taking Lamotrigine. Twenty women
      were randomized to receive the educational handout and 22 women were randomized
      to usual care. We found no statistical difference in the groups with regard to
      age, ethnicity or level of education. We found a significantly higher improvement
      in quiz scores in the educational handout group (3.65 point increase) compared to
      the usual care group (0.68 point increase) as calculated by the Student's two
      sample t test (p<.001). CONCLUSIONS: An educational handout on drug interactions
      and contraceptives resulted in increased short-term information retention on this
      topic among reproductive-age female epilepsy patients. IMPLICATIONS: This pilot
      study highlights the need for further larger studies to evaluate the impact of
      educational interventions on improving patient knowledge about the drug
      interaction of AEDs and hormonal contraceptives.

PMID- 26197262
TI  - Safety of first-trimester uterine evacuation in the outpatient setting for women
      with common chronic conditions.
AB  - OBJECTIVE: We compared complications of outpatient first-trimester uterine
      evacuation between women with medical comorbidities and healthy peers. STUDY
      DESIGN: We examined the medical histories and procedure outcomes of women
      receiving first-trimester uterine evacuations between 01/02/2009 and 03/07/2014.
      We compared women without medical problems to those reporting diabetes,
      hypertension, obesity (body mass index >=30.0 or weight >=200 lbs), HIV,
      epilepsy, asthma, thyroid disease and/or bleeding/clotting disorders. We compared
      incidence of any of the following: resuction, uterine perforation, estimated
      blood loss >100 cc and cervical laceration. RESULTS: A total of 1960 women met
      inclusion criteria; 597 (30%) had >=1 comorbidity. When compared to women without
      medical morbidities, women with common chronic conditions were older (28.3+/-6.7
      vs. 27.3+/-6.7 years, p<.01), less likely to be primigravid (29.1% vs. 35.7%,
      p<.01) and more likely to have had a prior cesarean delivery (24.9% vs. 15.7%,
      p<.001). Gestational age and indication for evacuation were similar for the
      groups. The overall complication rate was 2.9%. There was no difference in
      complications between the group of patients with at least one comorbidity
      compared to the group of women without any comorbidity (OR=0.9, 95% CI 0.5, 1.6).
      Additionally, there were no specific medical comorbidities that led to an
      increased complication rate. The only significant predictor of complication was
      history of cesarean delivery (OR=1.9, 95% CI 1.1, 3.4). CONCLUSION: Women with
      common chronic conditions undergoing outpatient first-trimester uterine
      evacuation do not appear to be at greater risk of complications compared to
      healthy peers. While a careful medical history is always required, providers may
      feel reassured that complications remain infrequent. IMPLICATIONS: Women with
      common chronic conditions undergoing outpatient first-trimester uterine
      evacuation do not appear to be at greater risk of complications compared to
      healthy peers.

PMID- 26197261
TI  - Associations of hormonal contraceptive use with measures of HIV disease
      progression and antiretroviral therapy effectiveness.
AB  - OBJECTIVE: To examine the associations between hormonal contraceptive use and
      measures of HIV disease progression and antiretroviral treatment (ART)
      effectiveness. STUDY DESIGN: A prospective cohort study of women with prevalent
      HIV infection in St. Petersburg, Russia, was conducted. After contraceptive
      counseling, participants chose to use combined oral contraceptives (COCs), depot
      medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male
      condoms for pregnancy prevention. Among participants not using ART at enrollment,
      we used multivariate Cox regression to assess the association between current
      (time-varying) contraceptive use and disease progression, measured by the primary
      composite outcome of CD4 decline to <350 cells/mm(3), ART initiation or death.
      Among participants using ART at enrollment, we used linear mixed models to
      estimate the predicted mean CD4 change at select time points by contraceptive
      method. RESULTS: During a total of 5233 months follow-up among participants not
      using ART with enrollment CD4 >=350 cells/mm(3) (n=315), 97 experienced disease
      progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95%
      confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was
      associated with a statistically significant increased risk for disease
      progression compared with use of nonhormonal methods (IUD or condoms). Among
      participants using ART at enrollment (n=77), we found no statistically
      significant differences in the predicted mean changes in CD4 cell count comparing
      current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. CONCLUSION:
      Hormonal contraceptive use was not significantly associated with measures of HIV
      disease progression or ART effectiveness among women with prevalent HIV
      infection. IMPLICATIONS: Hormonal contraceptive use was not significantly
      associated with measures of HIV disease progression or ART effectiveness among
      women with prevalent HIV infection.

PMID- 26197263
TI  - Contraception in women with cystic fibrosis: a systematic review of the
      literature.
AB  - OBJECTIVE: To perform a systematic review of the literature to examine original
      research on contraception in women with cystic fibrosis (CF) with a specific
      focus on safety, efficacy, non-contraceptive benefits, and utilization patterns
      in this population. STUDY DESIGN: We searched PubMed and Embase databases for any
      peer-reviewed original research in English on the use of contraception in women
      with CF. RESULTS: We identified 241 unique citations. After title review and
      exclusion of articles not reporting original data, 18 publications were included
      in the final review, with at least two articles for each area of focus. Limited
      evidence indicates that oral contraceptive pills are likely safe and efficacious
      in women with CF. Hormonal contraception may reduce pulmonary exacerbation rates
      and decrease need for antibiotics, suggesting non-contraceptive benefits. Women
      with CF utilize birth control at similar rates as the general population, and
      oral contraceptive pills and condoms are the most commonly used methods.
      CONCLUSIONS: Data on the safety, efficacy, and non-contraceptive benefits of
      hormonal contraception in women with CF are scant. Based on the limited data,
      hormonal contraception seems to be safe and efficacious and may provide
      noncontraceptive benefits. Further high-quality data from disease-specific
      research are required to better inform contraceptive decision-making among women
      with CF.

PMID- 26197264
TI  - The influence of trust in health care systems on postabortion contraceptive
      choice.
AB  - OBJECTIVES: This study investigates whether trust in the health care system or
      other patient-level characteristics are associated with interest in immediate
      initiation of long-acting reversible contraception (LARC) after abortion. STUDY
      DESIGN: A structured, self-administered survey was provided to English-speaking
      women 18 years or older presenting to a reproductive health center in the
      Southeastern United States for first-trimester surgical abortion. The survey
      collected information about patient characteristics, choice of postabortion
      contraception, health literacy and trust in the health care system. Trust was
      measured using a 17-item, previously validated survey and was treated as the
      primary independent variable. Our primary outcome variable is interest in
      immediate LARC placement postabortion. Statistical analysis was performed using
      Chi-square tests, Student's t tests and logistic regression with SAS(r) 9.2.
      RESULTS: Of 162 respondents who completed the survey, 24% planned to use LARC
      postabortion, which increased to 37% if LARC placement was available on the day
      of their abortion. The mean trust score was 59+/-8 (possible score of 17-85) and
      did not differ significantly between women who indicated an interest in immediate
      LARC placement postabortion and those who did not (p=.9). Women with a history of
      a prior birth were 3.4 times more likely to indicate interest in immediate
      postabortion LARC than others (adjusted odds ratio 3.42, 95% confidence interval
      1.63, 7.18). CONCLUSION: Desire to accept LARC immediately postabortion is
      associated with history of a prior birth but not with trust in the health care
      system or other demographic variables. Participant interest in postabortion LARC
      varied based on immediate device availability. IMPLICATIONS: This research
      underscores the importance of policies and clinical practices that promote access
      to LARC methods on the day of an abortion. Further research is needed to
      elucidate factors that correlate with choice of LARC postabortion.

PMID- 26197265
TI  - Contraceptive service needs of women with young children presenting for pediatric
      care.
AB  - OBJECTIVES: The primary objective of this study is to characterize the need for
      contraceptive services and contraceptive method use among women with young
      children presenting to child health clinics. A secondary objective is to
      characterize the factors, including access to care and health needs, that exist
      in this population and to evaluate their association with contraceptive method
      use. STUDY DESIGN: This is a cross-sectional study of women with children under
      age 36 months presenting to four child health practices in the Baltimore,
      Maryland, area. Participating women completed a survey to assess desire for
      pregnancy, contraceptive method use and related characteristics. RESULTS: A total
      of 238 participants (82%) were in need of contraceptive services (fertile and not
      desiring pregnancy). Overall, 59 (25%) of women in need were not using a
      contraceptive method (unmet need) and 79 (33%) were using a highly effective
      method (implant or intrauterine device). Factors associated with lower odds of
      unmet need for contraceptive services included attendance at a routine postpartum
      visit and visiting a healthcare provider to discuss contraception after
      pregnancy. Approximately half of index pregnancies were unintended and this was
      the only health factor associated with greater odds of using of a highly
      effective contraceptive method. CONCLUSIONS: Most women presenting with young
      children for pediatric care indicated that they were not currently trying to
      become pregnant and reported current methods of pregnancy prevention that ranged
      from none to highly effective. Women who had not sought postpregnancy
      contraceptive care were more likely to have unmet need for contraceptive
      services. IMPLICATIONS: Child health clinics may be a novel site for providing
      contraceptive care to women with children as part of a strategy to reduce
      unplanned pregnancies.

PMID- 26197266
TI  - The role of national policies and mental health care systems in the development
      of community care and community support: an international analysis.
AB  - BACKGROUND: The development of adequate community support of persons with severe
      mental health problems is an ongoing effort. National policies and national
      health and social care systems play an important role in the effectiveness of
      these efforts. AIMS: To get a better understanding of the ways in which national
      policies and (mental) health care systems can enhance the development of
      community support and social inclusion for people with severe mental illness.
      METHOD: A comparison was made between the experiences of 75 key persons on
      regional community support development regarding national policies and systems in
      Denmark, England and the Netherlands respectively. RESULTS: Four themes stood out
      as being particularly instrumental in the development of community support: -
      implementation of a national policy on social inclusion, - development of a
      national framework of responsibilities, entitlements and services, - solid
      funding and social inclusion incentivizing reimbursement systems, - integrated
      care. CONCLUSION: National governments do have opportunities to take or retake
      the lead to ensure that community support and social inclusion of persons with
      severe mental illness health problems are not just ideological slogans but solid
      policy.

PMID- 26197267
TI  - Brain networks of affective mentalizing revealed by the tear effect: The
      integrative role of the medial prefrontal cortex and precuneus.
AB  - Affective mentalizing involves the integration of various social signals in order
      to infer the affective states of others. Previous neuroimaging studies have shown
      that the medial prefrontal cortex, the precuneus/posterior cingulate cortex, and
      the temporo-parietal junction constitute the core affective mentalizing network.
      However, the relative contributions of these regions to affective mentalizing
      remain unclear. We used functional magnetic resonance imaging to investigate
      which of these nodes are involved in the integration of two social signals:
      emotional tears and facial expressions. We assumed that this integration would
      produce a supra-additive effect, indicated by greater activity than the sum of
      the effects of the individual social signals. Female subjects rated the sadness
      of faces with either tears or tear-like circles, and either sad or neutral
      expressions. We observed the supra-additive effect in the medial prefrontal
      cortex and precuneus/posterior cingulate cortex but not in the temporo-parietal
      junction. These results indicate that the medial prefrontal cortex and
      precuneus/posterior cingulate cortex play an important role in integrating tears
      and facial expressions during affective mentalizing. 

PMID- 26197268
TI  - Hospital Resource Utilization and Patient Outcomes Associated with Respiratory
      Viral Testing in Hospitalized Patients.
AB  - Testing patients for respiratory viruses should guide isolation precautions and
      provide a rationale for antimicrobial drug therapies, but few studies have
      evaluated these assumptions. To determine the association between viral testing,
      patient outcomes, and care processes, we identified adults hospitalized with
      respiratory symptoms from 2004 through 2012 at a large, academic, tertiary
      hospital in Canada. Viral testing was performed in 11% (2,722/24,567) of hospital
      admissions and was not associated with reduced odds for death (odds ratio 0.90,
      95% CI 0.76-1.10) or longer length of stay (+1 day for those tested). Viral
      testing resulted in more resource utilization, including intensive care unit
      admission, but positive test results were not associated with less antibiotic use
      or shorter duration of isolation. Results suggest that health care providers do
      not use viral test results in making management decisions at this hospital.
      Further research is needed to evaluate the effectiveness of respiratory infection
      control policies. 

PMID- 26197269
TI  - Sox5 and Th17 cell differentiation.

PMID- 26197270
TI  - Cellular MicroRNA Let-7a Suppresses KSHV Replication through Targeting MAP4K4
      Signaling Pathways.
AB  - BACKGROUND: Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is the etiologic
      agent of KS, the most common AIDS-related malignancy. The majority of KS tumor
      cells harbor latent KSHV virus but only a small percentage undergoes spontaneous
      lytic replication. Viral reactivation from latency is crucial for the
      pathogenesis and development of KS, but the cellular mechanisms underlying the
      switch between viral latency and replication are not well understood. METHODS:
      The level of let-7 miRNAs and MAP4K4 in KSHV infected 293T cells were quantified
      by real-time PCRs. Let-7 expression was silenced by the miRNA sponge technique.
      In let-7a transfected 293T cells, the expression of MAP4K4 was measured by real
      time PCR and western blot. Luciferease expression was employed to examine the
      effect of let-7a on the 3'-untranslated region (UTR) of the MAP4K4 gene in 293T
      cells. Real-time PCR was used to quantify the KSHV copy numbers in BC-3 cells in
      which the expression of let-7a and/or MAP4K4 were altered. Finally, ERK, JNK and
      p38 protein production and their phosphorylation status were detected by western
      blots in let-7a or MAP4K4 transfected BCBL-1 cells. RESULTS: The expression of
      microRNA let-7 was dramatically decreased in KSHV infected 293T cells, but that
      of MAP4K4 was increased significantly. Let-7a is physically associated with and
      targets the MAP4K4 3'UTR, and inhibits MAP4K4 expression at both mRNA and protein
      levels. MAP4K4 stimulates KSHV reactivation from latency, whereas let-7a inhibits
      the function of MAP4K4 by reversing the function of MAP4K4 on JNK, phospho-JNK
      and phospho-ERK1/2 levels. CONCLUSION: Our results establish that let-7a
      specifically suppresses MAP4K4 expression, and further inhibits KSHV reactivation
      by interfering with the function of MAP4K4 on the MAPK pathway, highlighting let
      7a as a potential treatment for KS.

PMID- 26197271
TI  - Melatonin ameliorates oxidative damage induced by maternal lead exposure in rat
      pups.
AB  - During the particular period of cerebellum development, exposure to lead (Pb)
      decreases cerebellum growth and can result in selective loss of neurons. The
      detection and prevention of Pb toxicity is a major international public health
      priorities. This research study was conducted to evaluate the effects of
      melatonin, an effective antioxidant and free radical scavenger, on Pb induced
      neurotoxicity and oxidative stress in the cerebellum. Pb exposure was initiated
      on gestation day 5 with the addition of daily doses of 0.2% lead acetate to
      distilled drinking water and continues until weaning. Melatonin (10mg/kg) was
      given once daily at the same time. 21 days after birth, several antioxidant
      enzyme activities including superoxide dismutase (SOD) and glutathione peroxidase
      (GPx) were assayed. Thiobarbituric acid reactive substance (TBARS) levels were
      measured as a marker of lipid peroxidation. Rotarod and locomotor activity tests
      were performed on postnatal days (PDs) 31-33 and a histological study was
      performed after completion of behavioral measurements on PD 33. The results of
      the present work demonstrated that Pb could induce lipid peroxidation, increase
      TBARS levels and decrease GPx and SOD activities in the rat cerebellum. We also
      observed that Pb impaired performance on the rotarod and locomotor activities of
      rats. However, treatment with melatonin significantly attenuated the motoric
      impairment and lipid peroxidation process and restored the levels of
      antioxidants. Histological analysis indicated that Pb could decrease Purkinje
      cell count and melatonin prevented this toxic effect. These results suggest that
      treatment with melatonin can improve motor deficits and oxidative stress by
      protecting the cerebellum against Pb toxicity.

PMID- 26197272
TI  - A New Pose Estimation Algorithm Using a Perspective-Ray-Based Scaled Orthographic
      Projection with Iteration.
AB  - Pose estimation aims at measuring the position and orientation of a calibrated
      camera using known image features. The pinhole model is the dominant camera model
      in this field. However, the imaging precision of this model is not accurate
      enough for an advanced pose estimation algorithm. In this paper, a new camera
      model, called incident ray tracking model, is introduced. More importantly, an
      advanced pose estimation algorithm based on the perspective ray in the new camera
      model, is proposed. The perspective ray, determined by two positioning points, is
      an abstract mathematical equivalent of the incident ray. In the proposed pose
      estimation algorithm, called perspective-ray-based scaled orthographic projection
      with iteration (PRSOI), an approximate ray-based projection is calculated by a
      linear system and refined by iteration. Experiments on the PRSOI have been
      conducted, and the results demonstrate that it is of high accuracy in the six
      degrees of freedom (DOF) motion. And it outperforms three other state-of-the-art
      algorithms in terms of accuracy during the contrast experiment. 

PMID- 26197273
TI  - Reduced Right Ventricular Function Predicts Long-Term Cardiac Re-Hospitalization
      after Cardiac Surgery.
AB  - BACKGROUND: The significance of right ventricular ejection fraction (RVEF),
      independent of left ventricular ejection fraction (LVEF), following isolated
      coronary artery bypass grafting (CABG) and valve procedures remains unknown. The
      aim of this study is to examine the significance of abnormal RVEF by cardiac
      magnetic resonance (CMR), independent of LVEF in predicting outcomes of patients
      undergoing isolated CABG and valve surgery. METHODS: From 2007 to 2009, 109
      consecutive patients (mean age, 66 years; 38% female) were referred for pre
      operative CMR. Abnormal RVEF and LVEF were considered <35% and <45%,
      respectively. Elective primary procedures include CABG (56%) and valve (44%).
      Thirty-day outcomes were perioperative complications, length of stay, cardiac re
      hospitalizations and early mortaility; long-term (> 30 days) outcomes included,
      cardiac re-hospitalization, worsening congestive heart failure and mortality.
      Mean clinical follow up was 14 months. FINDINGS: Forty-eight patients had reduced
      RVEF (mean 25%) and 61 patients had normal RVEF (mean 50%) (p<0.001). Fifty-four
      patients had reduced LVEF (mean 30%) and 55 patients had normal LVEF (mean 59%)
      (p<0.001). Patients with reduced RVEF had a higher incidence of long-term cardiac
      re-hospitalization vs. patients with normal RVEF (31% vs.13%, p<0.05). Abnormal
      RVEF was a predictor for long-term cardiac re-hospitalization (HR 3.01 [CI 1.5
      7.9], p<0.03). Reduced LVEF did not influence long-term cardiac re
      hospitalization. CONCLUSION: Abnormal RVEF is a stronger predictor for long-term
      cardiac re-hospitalization than abnormal LVEF in patients undergoing isolated
      CABG and valve procedures.

PMID- 26197274
TI  - Monoclonal Antibodies to Lipopolysaccharide O Antigens of Enterohemorrhagic
      Escherichia coli Strains in Serogroups O26, O45, O103, O111, O121, and O145.
AB  - Non-O157 enterohemorrhagic Escherichia coli in priority serogroups O26, O45,
      O103, O111, O121, and O145 are increasingly recognized as important human
      pathogens. In the present study, a panel of monoclonal antibodies (MAbs) to the
      lipopolysaccharide O antigens of E. coli in serogroups O26, O45, O103, O111,
      O121, and O145 was produced. The specificity was evaluated by examining the
      reactivity of the MAbs with 50 E. coli strains and 42 non-E. coli bacteria, and
      several MAbs highly specific for E. coli strains in each of the six non-O157
      priority serogroups were identified. The use of these highly specific MAbs may be
      of considerable value for determining whether an E. coli isolate belongs to one
      of the six priority non-O157 serogroups, for developing specific detection assays
      for these organisms, and for characterizing the lipopolysaccharide O antigens of
      isolates in these serogroups. 

PMID- 26197275
TI  - Inoculation Preparation Affects Survival of Salmonella enterica on Whole Black
      Peppercorns and Cumin Seeds Stored at Low Water Activity.
AB  - Salmonellosis has been increasingly associated with contaminated spices.
      Identifying inoculation and stabilization methods for Salmonella on whole spices
      is important for development of validated inactivation processes. The objective
      of this study was to examine the effects of inoculation preparation on the
      recoverability of Salmonella enterica from dried whole peppercorns and cumin
      seeds. Whole black peppercorns and cumin seeds were inoculated with S. enterica
      using one dry transfer method and various wet inoculation methods: immersion of
      spice seeds in tryptic soy broth (TSB) plus Salmonella for 24 h (likely leading
      to inclusion of Salmonella in native microbiota biofilms formed around the
      seeds), application of cells grown in TSB, and/or application of cells scraped
      from tryptic soy agar (TSA). Postinoculation seeds were dried to a water activity
      of 0.3 within 24 h and held for 28 days. Seeds were sampled after drying (time 0)
      and periodically during the 28 days of storage. Salmonella cells were enumerated
      by serial dilution and plated onto xylose lysine Tergitol (XLT4) agar and TSA.
      Recovery of Salmonella was high after 28 days of storage but was dependent on
      inoculation method, with 4.05 to 6.22 and 3.75 to 8.38 log CFU/g recovered from
      peppercorns and cumin seeds, respectively, on XLT4 agar. The changes in surviving
      Salmonella (log CFU per gram) from initial inoculation levels after 28 days were
      significantly smaller for the biofilm inclusion method (+0.142pepper,
      +0.186cumin) than for the other inoculation methods (-0.425pepper, -2.029cumin
      for cells grown on TSA; -0.641pepper, -0.718cumin for dry transfer; -1.998pepper
      for cells grown in TSB). In most cases, trends for reductions of total aerobic
      bacteria were similar to those of Salmonella. The inoculation method influenced
      the recoverability of Salmonella from whole peppercorns and cumin seeds after
      drying. The most stable inoculum strategies were dry transfer, 24-h incubation of
      Salmonella and spices in TSB (i.e., potential inclusion of Salmonella within
      native microbiota biofilms), and inoculation of Salmonella cells grown on TSA
      subsequent to drying. However, with the dry transfer method it was difficult to
      obtain the large amount of inoculum needed for inactivation studies. 

PMID- 26197276
TI  - Preharvest Salmonella Detection for Evaluation of Fresh Ground Poultry Product
      Contamination.
AB  - Salmonella is an important economic and public health concern for the poultry
      industry. Fresh ground product has been linked with multiple salmonellosis
      outbreaks in humans. Exposure can be controlled by proper handling and
      preparation by consumers; however, the industry desires to minimize carriage
      levels in the final product. A substantial obstacle in reducing product
      contamination stems from limitations in diagnostic methodologies. Detection of
      Salmonella contamination currently requires extended incubation periods, and by
      the time test results are available, the fresh product has reached retail
      shelves. The goal of this study was to develop a preharvest diagnostic protocol
      for the evaluation of ground product contamination. The turkey processing plant
      where this research was conducted had previously established Salmonella screening
      (BAX system) of ground product, thus providing an opportunity for preharvest
      sample comparison. Drag swabs were collected from live-haul trailers entering the
      processing plant over a 12-month period. The swabs were added to modified
      buffered peptone water and incubated at 40 degrees C. After incubation for 6 h or
      overnight, samples were tested for the presence of Salmonella with the DNAble
      assay and related to ground turkey samples from corresponding lots. The linear
      relationship for the percentage of Salmonella-positive live-haul trailers was
      significant for both the 6-h (slope = 1.02, R(2) = 0.96, and P < 0.0001) and
      overnight (slope = 0.35, R(2) = 0.93, and P = 0.0015) incubations, with the
      percentage of Salmonella-positive ground turkey samples. These data indicate that
      preharvest screening provides a meaningful evaluation of product contamination.
      Additionally, the 6-h incubation protocol is rapid enough to allow for product
      mitigation and could potentially aid in the reduction of future salmonellosis
      outbreaks. 

PMID- 26197277
TI  - Escherichia coli O157:H7 Outbreak Associated with Restaurant Beef Grinding.
AB  - Escherichia coli O157:H7 is a common cause of foodborne illness in the United
      States. Beef ground at establishments regulated by the U.S. Department of
      Agriculture, Food Safety and Inspection Service is routinely tested for E. coli
      O157:H7. Prior to December 2013, boxed beef product (wholesale cuts of beef, such
      as beef loin, packaged into bags and boxed for shipping) was not always tested
      for this pathogen. Downstream processors or retailers may grind the product; and,
      if the ground beef is not cooked to the recommended temperature, pathogens on the
      exterior of the beef introduced to the interior through grinding may survive. On
      18 October 2013, the Allegheny County Health Department identified two E. coli
      O157:H7 cases, both of whom were food handlers at restaurant A, a restaurant that
      ground locally produced boxed beef for hamburgers on site. Case finding was
      conducted through public messaging, employee surveys, and disease surveillance.
      All potential cases were interviewed using a standard questionnaire. A confirmed
      case was defined as laboratory-confirmed E. coli O157:H7 with exposure to
      restaurant A. A probable case was defined as a patient with compatible symptoms
      and exposure to restaurant A but without laboratory confirmation. All human and
      food isolates were characterized by pulsed-field gel electrophoresis and
      multilocus variable-number tandem repeat analysis. The analysis identified 14
      confirmed and 10 probable cases of E. coli; 18 nonintact ground beef samples
      tested positive for E. coli O157:H7. Nine confirmed cases were restaurant A
      employees. All confirmed cases recalled eating a restaurant A hamburger in the 10
      days before illness onset; most cases reported consuming medium to rare
      hamburgers. Multiple pulsed-field gel electrophoresis and multilocus variable
      number tandem repeat analysis patterns were identified among both the human and
      ground beef isolates, and the patient isolates matched those found in ground beef
      samples. Restaurant A voluntarily closed for 1.5 days, changed beef suppliers,
      ceased grinding beef in-house, and has had no new cases since reopening. 

PMID- 26197278
TI  - Control of Salmonella Cross-Contamination between Green Round Tomatoes in a Model
      Flume System.
AB  - Tomato Best Management Practices require Florida packers to treat tomatoes in a
      flume system containing at least 150 ppm of free chlorine or other approved
      sanitizer. However, research is needed to determine the ability of these
      sanitizers to prevent the transfer of pathogens from contaminated to
      uncontaminated tomatoes, particularly under realistic packinghouse conditions.
      The goal of this research was to assess the minimum levels of sanitizer needed to
      prevent Salmonella cross-contamination between tomatoes in a model flume system
      under clean conditions and conditions where organic matter was added. Inoculated
      tomatoes (ca. 8.3 log CFU per tomato) were treated along with uninoculated
      tomatoes in a model flume system containing 0, 10, or 25 ppm of hypochlorous acid
      (HOCl) under organic loading conditions of 0, 500, or 4,000 ppm of chemical
      oxygen demand (COD). In the absence of HOCl, uninoculated tomatoes were highly
      contaminated (ca. 5 log CFU per tomato) by 15 s. No contamination was detectable
      (<2 log CFU per tomato) on uninoculated tomatoes when HOCl was present, except
      with 10 ppm at 4,000 ppm of COD, suggesting failure of 10 ppm of HOCl as a
      sanitizer under very high organic loading conditions. In the presence of HOCl or
      peroxyacetic acid, Salmonella was undetectable (<1 log CFU/ml) in the model flume
      water samples after 2 and 30 s, respectively. Upon enrichment, none of the
      uninoculated tomatoes treated with 25 ppm of HOCl for 120 s were positive for
      Salmonella, even in the presence of organic loading at 500 ppm of COD. Based on
      these findings, 25 ppm of HOCl may be adequate to prevent cross-contamination
      when the concentration is properly maintained, COD does not exceed 500 ppm, and
      tomatoes are treated for at least 120 s. Further validation in a larger
      commercial setting and using higher organic loading levels is necessary because
      managing HOCl at this low concentration is difficult, especially in a
      recirculating system. The use of less sanitizer by packers could reduce chemical
      and disposal costs. 

PMID- 26197279
TI  - Efficacy of Sanitizer Treatments on Survival and Growth Parameters of Escherichia
      coli O157:H7, Salmonella, and Listeria monocytogenes on Fresh-Cut Pieces of
      Cantaloupe during Storage.
AB  - For health reasons, people are consuming fresh-cut fruits with or without minimal
      processing and, thereby, exposing themselves to the risk of foodborne illness if
      such fruits are contaminated with bacterial pathogens. This study investigated
      survival and growth parameters of Escherichia coli O157:H7, Salmonella, Listeria
      monocytogenes, and aerobic mesophilic bacteria transferred from cantaloupe rind
      surfaces to fresh-cut pieces during fresh-cut preparation. All human bacterial
      pathogens inoculated on cantaloupe rind surfaces averaged ~4.8 log CFU/cm(2), and
      the populations transferred to fresh-cut pieces before washing treatments ranged
      from 3 to 3.5 log CFU/g for all pathogens. A nisin-based sanitizer developed in
      our laboratory and chlorinated water at 1,000 mg/liter were evaluated for
      effectiveness in minimizing transfer of bacterial populations from cantaloupe
      rind surface to fresh-cut pieces. Inoculated and uninoculated cantaloupes were
      washed for 5 min before fresh-cut preparation and storage of fresh-cut pieces at
      5 and 10 degrees C for 15 days and at 22 degrees C for 24 h. In fresh-cut pieces
      from cantaloupe washed with chlorinated water, only Salmonella was found (0.9 log
      CFU/g), whereas E. coli O157:H7 and L. monocytogenes were positive only by
      enrichment. The nisin-based sanitizer prevented transfer of human bacteria from
      melon rind surfaces to fresh-cut pieces, and the populations in fresh-cut pieces
      were below detection even by enrichment. Storage temperature affected survival
      and the growth rate for each type of bacteria on fresh-cut cantaloupe. Specific
      growth rates of E. coli O157:H7, Salmonella, and L. monocytogenes in fresh-cut
      pieces were similar, whereas the aerobic mesophilic bacteria grew 60 to 80 %
      faster and had shorter lag phases. 

PMID- 26197280
TI  - Determination of Sources of Escherichia coli on Beef by Multiple-Locus Variable
      Number Tandem Repeat Analysis.
AB  - The possible origin of Escherichia coli found on cuts and trimmings in the
      breaking facility of a beef packing plant was examined using multiple-locus
      variable-number tandem repeat analysis. Coliforms and E. coli were enumerated in
      samples obtained from 160 carcasses that would enter the breaking facility when
      work commenced and after each of the three production breaks throughout the day,
      from the conveyor belt before work and after each break, and from cuts and
      trimmings when work commenced and after each break. Most samples yielded no E.
      coli, irrespective of the surface types. E. coli was recovered from 7 (<5%)
      carcasses, at numbers mostly <=1.0 log CFU/160,000 cm(2). The log total numbers
      of E. coli recovered from the conveyor belt, cuts, and trimmings were mostly
      between 1 and 2 log CFU/80,000 cm(2). A total of 554 E. coli isolates were
      recovered. Multiple-locus variable-number tandem repeat analysis of 327 selected
      isolates identified 80 distinct genotypes, with 37 (46%) each containing one
      isolate. However, 28% of the isolates were of genotypes that were recovered from
      more than one sampling day. Of the 80 genotypes, 65 and 2% were found in one or
      all four sampling periods throughout the day. However, they represented 23 and
      14% of the isolates, respectively. Of the genotypes identified for each surface
      type, at least one contained >=9 isolates. No unique genotypes were associated
      with carcasses, but 10, 17, and 19 were uniquely associated with cuts, trimmings,
      and the belt, respectively. Of the isolates recovered from cuts, 49, 3, and 19%
      were of genotypes that were found among isolates recovered from the belt,
      carcasses, or both the belt and carcasses, respectively. A similar composition
      was found for isolates recovered from trimmings. These findings show that the E.
      coli found on cuts and trimmings at this beef packing plant mainly originated
      from the conveyor belt and that small number of E. coli strains survived the
      daily cleaning and sanitation process, thus persisting in the plant. 

PMID- 26197281
TI  - Evaluation of Propidium Monoazide and Quantitative PCR To Quantify Viable
      Campylobacter jejuni Biofilm and Planktonic Cells in Log Phase and in a Viable
      but Nonculturable State.
AB  - Despite being considered fragile and fastidious, Campylobacter jejuni remains the
      leading cause of bacterial gastroenteritis in the developed world. C. jejuni
      survives stresses by forming biofilms or entering a viable but nonculturable
      (VBNC) state. To investigate the number of viable cells in samples exposed to low
      nutrient and temperature stress, a novel method, propidium monoazide quantitative
      PCR (PMAqPCR), was compared with Bac Light biovolume analysis and conventional
      plate counting for the enumeration of C. jejuni-removed biofilm cells and
      separately grown planktonic cells in late log phase (24 h). There were no
      significant differences between viable cell counts obtained using PMAqPCR and
      those from plate counts or Bac Light biovolume analyses for each sample,
      confirming that this method provides results consistent with those from accepted
      enumeration methods (P > 0.05). To induce a VBNC state, C. jejuni planktonic
      cells and dislodged and washed biofilm cells were separately incubated in
      phosphate-buffered saline at 4 degrees C for up to 60 days. Even when cells
      exposed to stress were provided with enrichment in Bolton broth before plating,
      treated biofilm cells lost culturability by day 10, whereas their planktonic
      counterparts remained culturable to day 60. The nonculturable biofilm cells
      remained viable in high numbers to day 60, and viable cell counts from the
      PMAqPCR (6.15 log cells per ml) were not significantly different from those
      obtained using the Bac Light assay (6.98 log cells per ml) (P > 0.05), confirming
      that this novel method is also reliable for cells exposed to stress for extended
      periods. PMAqPCR shows promise for analysis where C. jejuni exists in biofilms or
      in the VBNC state. Adopting PMAqPCR in routine monitoring, in conjunction with
      improved biofilm cell collection methods, will allow for more accurate
      enumeration of viable and potentially virulent cells, leading to improved
      sanitation and reduced incidence of infection. 

PMID- 26197282
TI  - Consumer Shell Egg Consumption and Handling Practices: Results from a National
      Survey.
AB  - Numerous cases and outbreaks of Salmonella infection are attributable to shell
      eggs each year in the United States. Safe handling and consumption of shell eggs
      at home can help reduce foodborne illness attributable to shell eggs. A
      nationally representative Web survey of 1,504 U.S. adult grocery shoppers was
      conducted to describe consumer handling practices and consumption of shell eggs
      at home. Based on self-reported survey data, most respondents purchase shell eggs
      from a grocery store (89.5%), and these eggs were kept refrigerated (not at room
      temperature; 98.5%). As recommended, most consumers stored shell eggs in the
      refrigerator (99%) for no more than 3 to 5 weeks (97.6%). After cracking eggs,
      48.1% of respondents washed their hands with soap and water. More than half of
      respondents who fry and/or poach eggs cooked them so that the whites and/or the
      yolks were still soft or runny, a potentially unsafe practice. Among respondents
      who owned a food thermometer (62.0%), only 5.2% used it to check the doneness of
      baked egg dishes when they prepared such a dish. Consumers generally followed two
      of the four core "Safe Food Families" food safety messages ("separate" and
      "chill") when handling shell eggs at home. To prevent Salmonella infection
      associated with shell eggs, consumers should improve their practices related to
      the messages "clean" (i.e., wash hands after cracking eggs) and "cook" (i.e.,
      cook until yolks and whites are firm and use a food thermometer to check doneness
      of baked egg dishes) when preparing shell eggs at home. These findings will be
      used to inform the development of science-based consumer education materials that
      can help reduce foodborne illness from Salmonella infection.

PMID- 26197283
TI  - Characterization of Enterococci from Food and Food-Related Settings.
AB  - Enterococcus species are ubiquitous in nature, exist at high levels in food, and
      can cause severe diseases in humans. Thus, surveillance of enterococci harboring
      antibiotic resistance and virulence factors in food and food-related environments
      is needed. In the present study, 89 samples from food and food processing
      surfaces were collected in a cheese factory, a swine slaughterhouse, and a
      supermarket, and 132 Enterococcus isolates were recovered. Most isolates were
      identified as E. faecalis, which is considered the most pathogenic member of this
      genus. Safety analysis covering antibiotic resistance revealed that all isolates
      were resistant to sulfamethoxazole-trimethoprim and sensitive to amoxicillin
      clavulanate, ampicillin, ciprofloxacin, gentamicin, levofloxacin, linezolid,
      nitrofurantoin, or teicoplanin. More than half of the isolates were resistant to
      quinupristin-dalfopristin, tetracycline, and bacitracin, and less than half were
      resistant to the other antibiotics evaluated. Regarding virulence factors, 52%
      the isolates were beta-hemolytic, 39% were gelatinase producers, and 45%
      contained the gelE gene. For the remaining genes evaluated, efaAfs was detected
      in more than half of the isolates, and agg, esp, and efaAfm were found in less
      than half of the isolates. The present investigation revealed that food-related
      enterococci obtained from very different settings have multidrug resistance and
      virulence factors, highlighting the importance of effective surveillance networks
      to avoid the spread of putative pathogenic enterococci. 

PMID- 26197284
TI  - Evaluation of Chitosan-Starch-Based Edible Coating To Improve the Shelf Life of
      Bod Ljong Cheese.
AB  - The objective of this work was to evaluate the effectiveness of antimicrobial
      edible coatings to improve the quality of Bod ljong cheese throughout 25 days of
      storage. Coatings were prepared using chitosan, water chestnut starch, and
      glycerol as a base matrix, together with several combinations of antimicrobial
      substances: Cornus officinalis fruit extract (COFE), pine needle essential oil
      (PNEO), and nisin. Application of coating on cheese decreased water loss, lipid
      oxidation, changes in headspace gas composition, and color. Moreover, the edible
      coatings with COFE or PNEO had increased antimicrobial activity and did not
      permit growth of microorganisms. COFE and PNEO are manufactured from food-grade
      materials so they can be consumed as an integral part of the cheese, which
      represents a competitive advantage over nonedible coatings. 

PMID- 26197285
TI  - Prevalence and Characterization of High Histamine-Producing Bacteria in Gulf of
      Mexico Fish Species.
AB  - Recent developments in detection and enumeration of histamine-producing bacteria
      (HPB) have created powerful molecular-based tools to better understand the
      presence of spoilage bacteria and conditions, resulting in increased risk of
      scombrotoxin fish poisoning. We examined 235 scombrotoxin-forming fish from the
      Gulf of Mexico for the presence of high HPB. Photobacterium damselae subsp.
      damselae was the most prevalent HPB (49%), followed by Morganella morganii (14%),
      Enterobacter aerogenes (4%), and Raoultella planticola (3%). The growth
      characteristics and histamine production capabilities of the two most prevalent
      HPB were further examined. M. morganii and P. damselae had optimum growth at 35
      degrees C and 30 to 35 degrees C and 0 to 2% and 1 to 3% NaCl, respectively. P.
      damselae produced significantly (P < 0.001) higher histamine than M. morganii in
      inoculated mahimahi and Spanish mackerel incubated at 30 degrees C for 24 h, but
      histamine production was not significantly different between the two HPB in
      inoculated tuna, possibly due to differences in muscle composition and salt
      content. Results in this study showed that P. damselae was the most prevalent
      high HPB in Gulf of Mexico fish. In addition, previously reported results using
      the traditional Niven's method may underreport the prevalence of P. damselae.
      Molecular-based methods should be used in addition to culture-based methods to
      enhance detection and enumeration of HPB. 

PMID- 26197286
TI  - Storage Time and Temperature Effects on Histamine Production in Tuna Salad
      Preparations.
AB  - Scombrotoxin fish poisoning (SFP), also known as histamine (Hst) poisoning, has
      been associated with consumption of scombroid-type fish, including tuna and tuna
      fish products. Preparation of commercial tuna salad contaminated with
      Hstproducing bacteria (HPB), combined with time-temperature abuse, can present a
      food safety hazard. A potential source of HPB is raw ingredients, such as celery
      and onions. The objectives of this study were to determine whether raw
      ingredients can be a source of HPB and to ascertain the effects of storage time
      (up to 4 days or 4 weeks) and temperature (4, 10, 18, 25, 30 degrees C) on growth
      and Hst production by high-HPB (>1,000 ppm of Hst) in tuna salad preparations.
      Pantoea-Erwinia, Erwinia persicinus, Erwinia spp., and Enterobacter pyrinus
      isolated from celery in this study were used to inoculate tuna salad and tuna
      salad with celery or onion. HPB numbers were 0.7 to 4.3 log most probable number
      per g higher in the presence of celery or onion versus plain tuna salad (3:1
      tuna:mayonnaise). E. pyrinus-inoculated plain tuna salad and tuna salad with
      celery and onion had >500 ppm of Hst after 2 days at 30 degrees C and 4 days at
      25 degrees C. E. pyrinus-inoculated salad with celery and onion had >500 ppm of
      Hst after 4 days at 18 degrees C and 2 weeks at 10 degrees C. Raw celery can
      introduce HPB into tuna salad, which can cause SFP if the product is time
      temperature abused. Tuna salad products must be refrigerated at <=4 degrees C to
      prevent growth and Hst production by the HPB used in this study, to protect
      consumers from potential SFP. 

PMID- 26197287
TI  - Infestation and Quantification of Ochratoxigenic Fungi in Barley and Wheat
      Naturally Contaminated with Ochratoxin A.
AB  - Cereal grains are a significant source of ochratoxin A (OTA) in the human diet.
      Multiple ochratoxigenic Aspergillus and Penicillium spp. have been reported as
      contaminants on various cereal grains around the world, although relatively few
      species dominate in any given location. Efforts to mitigate the risk of fungal
      contamination and OTA accumulation can be made pre- and postharvest. Still, a
      rapid and reliable screening method is sought that can be used to predict the OTA
      level of a sample and to inform risk assessments prior to processing. In this
      study, we assessed the efficacy of two OTA-related indices for OTA level
      prediction. Infestation rates were determined by direct plating for freshly
      harvested and stored barley, durum, and hard red spring wheat samples (n = 139)
      with known OTA levels. Presumptive ochratoxigenic isolates were tested for their
      ability to produce OTA. The nonribosomal peptide synthase (otanpsPN) involved in
      OTA biosynthesis was used to quantify ochratoxigenic fungi in barley and wheat.
      Viable Penicillium verrucosum was present in 45% of the samples. In total, 62.7%
      (n = 110) of the P. verrucosum isolates tested produced OTA on dichloran yeast
      extract sucrose 18% glycerol agar. Both OTA level and infestation rate (r =
      0.30), as well as OTA level and otanpsPN concentration (r = 0.56), were weakly
      correlated. Neither infestation rate nor otanpsPN concentration is a reliable
      predictor of OTA level in a sample. 

PMID- 26197288
TI  - Efficacy of Lytic Bacteriophage Preparation in Reducing Salmonella In Vitro, on
      Turkey Breast Cutlets, and on Ground Turkey.
AB  - The efficacy of the recently approved Salmonella lytic bacteriophage preparation
      (SalmoFresh) in reducing Salmonella enterica serotype Heidelberg on turkey breast
      cutlets and ground turkey was evaluated. In a broth model assay, the phage
      preparation completely inhibited the growth of four S. enterica serotypes
      (Salmonella Enteritidis, Salmonella Heidelberg, Salmonella Kentucky, and
      Salmonella Typhimurium) at 37 degrees C at a multiplicity of infection of 10,000
      PFU/CFU. At 4 degrees C in 0.1% peptone water (PW), phage treatment at a
      multiplicity of infection of 10,000 resulted in ca. 4.0-log CFU/ml reductions of
      Salmonella Enteritidis, Salmonella Heidelberg, and Salmonella Typhimurium. When
      raw turkey breast cutlets inoculated with Salmonella Heidelberg (~10(3) CFU/g)
      were treated with phage preparation (10(7) PFU/g) and stored at 4 degrees C, the
      phage treatment caused reductions of 0.8, 0.6, and 1.3 log CFU/g (P <= 0.05) of
      Salmonella Heidelberg on day 0, 1, and 7, respectively, compared with the counts
      in the control. However, no significant reduction of Salmonella Heidelberg (P >
      0.05) was observed in ground turkey when turkey meat pieces inoculated with
      Salmonella Heidelberg were surface treated with phage preparation (10(7) PFU/g)
      before grinding. These findings indicate that the bacteriophage preparation was
      effective in reducing Salmonella on turkey breast cutlets as a surface treatment
      but did not cause any reduction of Salmonella Heidelberg in ground turkey. 

PMID- 26197289
TI  - Rapid Detection of Campylobacter jejuni, Campylobacter coli, and Campylobacter
      lari in Fresh Chicken Meat and By-Products in Bangkok, Thailand, Using Modified
      Multiplex PCR.
AB  - A multiplex PCR assay for simultaneous detection and differentiation of
      Campylobacter jejuni, Campylobacter coli, and Campylobacter lari was developed
      and validated to assess the occurrence of these bacteria in fresh chicken meat
      and by-products in Bangkok, Thailand, by using a new combination of four
      previously published PCR primers for C. jejuni, C. coli, C. lari, and a universal
      16S rDNA gene as an internal control. The specificity was determined by using 13
      strains of other bacteria. With pure culture DNA, the detection limit was 0.017
      ng/PCR for C. jejuni and C. coli and was 0.016 ng/PCR for C. lari. It can detect
      10 CFU of C. jejuni, C. coli, and C. lari in 2 g of chicken meat within a 16-h
      enrichment time. Our multiplex PCR assay was applied for identification of
      Campylobacter spp. in 122 supermarket samples and 108 fresh market samples. Of
      the 230 samples evaluated by multiplex PCR, 54.0, 3.3, and 10.7% of supermarket
      samples were positive for C. jejuni, C. coli, and mixed C. jejuni and C. coli,
      respectively, and 56.5 and 33.3% of fresh market samples were positive for C.
      jejuni and mixed C. jejuni and C. coli, respectively. No sample was positive for
      C. lari. Fresh market samples had significantly higher C. jejuni and C. coli
      contamination than those from supermarkets (relative risk: 1.3; P = 0.0001).
      Compared with the culture method (a gold standard), the sensitivity, specificity,
      positive predictive value, negative predictive value, and diagnostic accuracy of
      multiplex PCR were 97.7, 86.8, 96.1, 92.0, and 95.2%, respectively. No
      significant difference was observed between results from two methods (P = 0.55).
      Therefore, the established multiplex PCR was not only rapid and easy to perform
      but had a high sensitivity and specificity to distinguish between C. jejuni, C.
      coli, and C. lari, even in samples containing mixed contamination. Our study
      indicated that fresh chicken meat and by-products from fresh markets were
      significantly less hygienic than those from supermarkets. 

PMID- 26197290
TI  - Effect of Sampling Plans on the Risk of Escherichia coli O157 Illness.
AB  - Australia exports about 150,000 to 200,000 tons of manufacturing beef to the
      United States annually. Each lot is tested for Escherichia coli O157 using the N
      60 sampling protocol, where 60 small pieces of surface meat from each lot of
      production are tested. A risk assessment of E. coli O157 illness from the
      consumption of hamburgers made from Australian manufacturing meat formed the
      basis to evaluate the effect of sample size and amount on the number of illnesses
      predicted. The sampling plans evaluated included no sampling (resulting in an
      estimated 55.2 illnesses per annum), the current N-60 plan (50.2 illnesses), N-90
      (49.6 illnesses), N-120 (48.4 illnesses), and a more stringent N-60 sampling plan
      taking five 25-g samples from each of 12 cartons (47.4 illnesses per annum).
      While sampling may detect some highly contaminated lots, it does not guarantee
      that all such lots are removed from commerce. It is concluded that increasing the
      sample size or sample amount from the current N-60 plan would have a very small
      public health effect. 

PMID- 26197291
TI  - Evaluation of Ice Slurries as a Control for Postharvest Growth of Vibrio spp. in
      Oysters and Potential for Filth Contamination.
AB  - Raw oyster consumption is the most common route of exposure for Vibrio spp.
      infections in humans. Vibriosis has been increasing steadily in the United States
      despite efforts to reduce the incidence of the disease. Research has demonstrated
      that ice is effective in reducing postharvest Vibrio spp. growth in oysters but
      has raised concerns of possible contamination of oyster meat by filth (as
      indicated by the presence of fecal coliform bacteria or Clostridium perfringens).
      This study examined the use of ice slurries (<4.5 degrees C) to reduce Vibrio
      growth. Ice slurries showed rapid internal cooling of oysters, from 23.9 degrees
      C (75 degrees F) to 10 degrees C (50 degrees F) within 12 min. The initial
      bacterial loads in the ice slurry waters were near the limits of detection.
      Following repeated dipping of oysters into ice slurries, water samples exhibited
      significant (P < 0.05) increases in median levels of fecal coliforms (9.5 most
      probable number [MPN]/100 ml), C. perfringens (280 MPN/100 ml), Vibrio vulnificus
      (11,250 MPN/ml), and total Vibrio parahaemolyticus (3,900 MPN/ml). The microbial
      load in oyster meat, however, was unchanged after 15 min of submergence, with no
      significant differences (P < 0.05) in levels of filth indicator (range, 250 to
      720 MPN/100 g) or Vibrio spp. (range, 9,000 to 20,000 MPN/g) bacteria. These
      results support the use of ice slurries as a postharvest application for rapid
      cooling of oysters to minimize Vibrio growth. 

PMID- 26197292
TI  - Comparison of a Four-Section Spindle and Stomacher for Efficacy of Detaching
      Microorganisms from Fresh Vegetables.
AB  - This study was undertaken to compare the effect of the spindle and stomacher for
      detaching microorganisms from fresh vegetables. The spindle is an apparatus for
      detaching microorganisms from food surfaces, which was developed in our
      laboratory. When processed with the spindle, food samples were barely disrupted,
      the original shape was maintained, and the diluent was clear, facilitating
      further detection analysis more easily than with stomacher treatment. The four
      section spindle consists of four sample bag containers (A, B, C, and D) to
      economize time and effort by simultaneously processing four samples. The aerobic
      plate counts (APC) of 50 fresh vegetable samples were measured following spindle
      and stomacher treatment. Correlations between the two methods for each section of
      the spindle and stomacher were very high (R(2) = 0.9828 [spindle compartment A;
      Sp A], 0.9855 [Sp B], 0.9848 [Sp C], and 0.9851 [Sp D]). One-tenth milliliter of
      foodborne pathogens suspensions was inoculated onto surfaces of food samples, and
      ratios of spindle-to-stomacher enumerations were close to 1.00 log CFU/g between
      every section of the spindle and stomacher. One of the greatest features of the
      spindle is that it can treat large-sized samples that exceed 200 g. Uncut whole
      apples, green peppers, potatoes, and tomatoes were processed by the spindle and
      by hand massaging by 2 min. Large-sized samples were also assayed for aerobic
      plate count and recovery of the three foodborne pathogens, and the difference
      between each section of the spindle and hand massaging was not significant (P >
      0.05). This study demonstrated that the spindle apparatus can be an alternative
      device for detaching microorganisms from all fresh vegetable samples for
      microbiological analysis by the food processing industry. 

PMID- 26197293
TI  - Microbiological Safety and Food Handling Practices of Seed Sprout Products in the
      Australian State of Victoria.
AB  - Seed sprouts have been implicated as vehicles for numerous foodborne outbreaks
      worldwide. Seed sprouts pose a unique food safety concern because of the ease of
      microbiological seed contamination, the inherent ability of the sprouting process
      to support microbial growth, and their consumption either raw or lightly cooked.
      To examine seed sprout safety in the Australian state of Victoria, a survey was
      conducted to detect specific microbes in seed sprout samples and to investigate
      food handling practices relating to seed sprouts. A total of 298 seed sprout
      samples were collected from across 33 local council areas. Escherichia coli was
      detected in 14.8%, Listeria spp. in 12.3%, and Listeria monocytogenes in 1.3% of
      samples analyzed. Salmonella spp. were not detected in any of the samples. A
      range of seed sprout handling practices were identified as potential food safety
      issues in some food businesses, including temperature control, washing practices,
      length of storage, and storage in proximity to unpackaged ready-to-eat
      potentially hazardous foods. 

PMID- 26197294
TI  - Detection and Quantification of Thermophilic Spore-Forming Moorella thermoacetica
      in Canned Beverages Using Real-Time PCR.
AB  - A quantitative real-time PCR assay was developed to specifically detect and
      quantify Moorella thermoacetica and/or Moorella thermoautotrophica from canned
      coffee beverages. Six different combinations of newly designed primers were
      examined, and primer pair v1-1F/v4R was found to specifically amplify M.
      thermoacetica and M. thermoautotrophica. The minimum detection sensitivity was 15
      fg of pure culture DNA from M. thermoacetica. Twenty commercial canned coffee
      beverages were then screened for the presence of M. thermoacetica, and two were
      shown to contain >1.3 and >1.0 CFU/ml, respectively. Therefore, the assay
      developed in this study may be useful for accurately tracking and quantifying M.
      thermoacetica and M. thermoautotrophica in beverage samples. 

PMID- 26197295
TI  - Effects of Gamma and Electron Beam Radiation on Brazil Nuts Artificially
      Inoculated with Aspergillus flavus.
AB  - The aim of this study was to evaluate the effects of gamma radiation (GR) and
      electron beam (EB) on Brazil nut samples contaminated with Aspergillus flavus.
      Fifty samples were spread with an A. flavus suspension and incubated at 30
      degrees C and a relative humidity of 93%. After 15 days of incubation, mycobiota
      and aflatoxin analysis were performed. The samples were divided into three groups
      (control, group 1, and group 2) that received radiation doses of 0 kGy (control)
      and 5 and 10 kGy each of GR and EB (groups 1 and 2). Noninoculated samples were
      irradiated with the same doses for sensory evaluation. The results showed that
      after 15 days of incubation, the average water activity of the samples was 0.80.
      The irradiation with GR and EB at doses of 5 and 10 kGy was able to eliminate A.
      flavus in Brazil nut samples. Aflatoxin analysis showed that EB doses of 5 and 10
      kGy reduced aflatoxin B1 levels by 53.32 and 65.66%, respectively, whereas the
      same doses of GR reduced the levels of this toxin by 70.61 and 84.15% compared
      with the level in the control groups. Sensory evaluation demonstrated that the
      texture and odor of irradiated Brazil nut samples were acceptable. The taste
      evaluation indicated that 5 kGy of GR was judged acceptable. The results
      highlight that both irradiation processes (5- and 10-kGy doses) showed efficiency
      in A. flavus and aflatoxin elimination. GR and EB treatments resulted in some
      alterations in the sensory attributes of samples with the doses used in this
      study; however, Brazil nut samples irradiated with 5-kGy GR doses were considered
      acceptable. 

PMID- 26197296
TI  - Bisphenol A and Three Other Bisphenol Analogues in Canned Fish Products from the
      Canadian Market 2014.
AB  - A sensitive and selective gas chromatography-mass spectrometry method was
      developed and validated for simultaneous analysis of bisphenol A (BPA) and three
      other bisphenols, bisphenol B (BPB), bisphenol E (BPE), and bisphenol F (BPF).
      This method was used to analyze samples of 52 canned fish products to follow up a
      previous study conducted 5 years ago to investigate any changes in BPA levels
      since then and levels of other bisphenols due to possible changes in can coating
      formulations. BPB and BPE were not detected in any of the 52 canned fish
      products, and BPF was detected in only four products at low levels from 1.8 to
      5.7 ng/g, indicating that BPA is likely still the dominant bisphenol used in
      current can coating formulations. BPA was detected in all 52 canned fish
      products, but at much lower levels compared with a previous study; levels ranged
      from 0.96 to 265 ng/g (average, 28 ng/g). The few products with high BPA levels
      (>100 ng/g) are exclusively from a new brand that has become available on the
      market only recently. Further analysis of canned fish products is planned in the
      future to capture any changes in BPA levels in these products and to update the
      exposure assessment of BPA due to consumption of canned fish products. 

PMID- 26197297
TI  - Synthesis and Characterization of Hapten-Protein Conjugates for Antibody
      Production against Cyanogenic Glycosides.
AB  - Consumption of cyanogenic plants can cause serious health problems for humans.
      The ability to detect and quantify cyanogenic glycosides, capable of generating
      cyanide, could contribute to prevention of cyanide poisoning from the consumption
      of improperly processed cyanogenic plants. Hapten-protein conjugates were
      synthesized with amygdalin and linamarin by using a novel approach. Polyclonal
      antibodies were generated by immunizing four New Zealand White rabbits with
      synthesized amygdalin-bovine serum albumin and linamarin-bovine serum albumin
      immunogen. This is the first time an antibody was produced against linamarin.
      Antibody titer curves were obtained from all the four rabbits by using a
      noncompetitive enzyme-linked immunosorbent assay. High antibody titer was
      obtained at dilutions greater than 1:50,000 from both immunogens. This new method
      is an important step forward in preventing ingestion of toxic cyanogenic
      glycosides. 

PMID- 26197298
TI  - Detection of Fish Bones in Cod Fillets by UV Illumination.
AB  - The presence of fish bones is now regarded as an important hazard in fishery
      products, and there is increasing demand for new analytical techniques to control
      it more effectively. Here, the fluorescent properties of cod bones under UV
      illumination were investigated, and the maximal wavelengths for excitation and
      emission were determined to be 320 nm and 515 nm, respectively, demonstrating
      significantly different fluorescence characteristics and much higher fluorescence
      intensity compared to those of fillet muscles. Based on the results, UV
      fluorescence-assisted candling for the detection of bones in fishery products was
      developed for the first time. Using cod fillets as samples, the detection ratio
      of this technique was calculated as 90.86%, significantly higher than that of
      traditional candling under daylight (76.78%). Moreover, the working efficiency of
      the new technique was about 26% higher than that of the traditional method. A UV
      fluorescence imaging framework was also developed, and a method for automatic
      identification of the fish bones in the cod fillets based on the linear
      discriminant analysis proposed by Fisher was preliminarily realized, but the
      detection ratio was demonstrated to be relatively poor compared to those of
      candling techniques. These results allow us to suggest UV-based methods as new
      and promising approaches for routine monitoring of bones in fishery products. 

PMID- 26197300
TI  - Children adapt their questions to achieve efficient search.
AB  - One way to learn about the world is by asking questions. We investigate how
      younger children (7- to 8-year-olds), older children (9- to 11-year-olds), and
      young adults (17- to 18-year-olds) ask questions to identify the cause of an
      event. We find a developmental shift in children's reliance on hypothesis
      scanning questions (which test hypotheses directly) versus constraint-seeking
      questions (which reduce the space of hypotheses), but also that all age groups
      ask more constraint-seeking questions when hypothesis-scanning questions are
      least likely to pay off: When the solution is one among equally likely
      alternatives (Study 1) or when the problem is difficult (Studies 1 and 2). These
      findings are the first to demonstrate that even young children dynamically adapt
      their strategies for inquiry to increase the efficiency of information search. 

PMID- 26197299
TI  - Bile diversion to the distal small intestine has comparable metabolic benefits to
      bariatric surgery.
AB  - Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and
      associated diabetes. Recent observations in humans suggest a contributing role of
      increased circulating bile acids in mediating such effects. Here we use a diet
      induced obesity (DIO) mouse model and compare metabolic remission when bile flow
      is diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham
      control). We find that only bile diversion to the ileum results in physiologic
      changes similar to RYGB, including sustained improvements in weight, glucose
      tolerance and hepatic steatosis despite differential effects on hepatic gene
      expression. Circulating free fatty acids and triglycerides decrease while bile
      acids increase, particularly conjugated tauro-beta-muricholic acid, an FXR
      antagonist. Activity of the hepatic FXR/FGF15 signalling axis is reduced and
      associated with altered gut microbiota. Thus bile diversion, independent of
      surgical rearrangement of the gastrointestinal tract, imparts significant weight
      loss accompanied by improved glucose and lipid homeostasis that are hallmarks of
      RYGB. 

PMID- 26197301
TI  - A new functional classification system (FGA/B) with prognostic value for glioma
      patients.
AB  - Despite advances in multimodal treatments, malignant gliomas remain characterized
      by a short survival time. Surgical treatment is accepted to be the first line of
      therapy, with recent studies revealing that maximal possible tumor reduction
      exerts significant impact on patient outcome. Consideration of tumor localization
      in relation to functionally eloquent brain areas has been gaining increasing
      importance. Despite existing assessment methods, the availability of a simple but
      reliable preoperative grading based on functional data would therefore prove to
      be indispensable for the prediction of postoperative outcome and hence for
      overall survival in glioma patients. We performed a clinical investigation
      comprising 322 patients with gliomas and developed a novel classification system
      of preoperative tumor status, which considers tumor operability based on two
      graduations (Friedlein Grading - FG): FGA with lesions at safe distance to
      eloquent regions which can be completely resected, and FGB referring to tumors
      which can only be partially resected or biopsied. Investigation of outcome
      revealed that FGA were characterized by a significantly longer overall survival
      time compared to FGB. We offer the opportunity to classify brain tumors in a
      dependable and reproducible manner. The FGA/B grading method provides high
      prognostic value with respect to overall survival time in relation to the extent
      of location-dependent tumor resection. 

PMID- 26197303
TI  - Expedited versus conservative approaches for vaginal delivery in breech
      presentation.
AB  - BACKGROUND: In a vaginal breech birth there may be benefit from rapid delivery of
      the baby to prevent progressive acidosis. However, this needs to be weighed
      against the potential trauma of a quick delivery. OBJECTIVES: The objective of
      this review was to assess the effects of expedited vaginal delivery (breech
      delivery from umbilicus to delivery of the head within one contraction) on
      perinatal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (31 May 2015) and reference lists of retrieved
      studies. SELECTION CRITERIA: Randomised trials of expedited vaginal breech
      delivery compared with delivery not routinely expedited in women undergoing
      vaginal breech delivery. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the one identified trial for inclusion.If studies are
      included in future updates, two review authors will assess risk of bias, extract
      data and check data for accuracy. MAIN RESULTS: No studies were included.
      AUTHORS' CONCLUSIONS: There is not enough evidence to evaluate the effects of
      expedited vaginal breech delivery.

PMID- 26197302
TI  - Dopamine effects on evidence gathering and integration.
AB  - BACKGROUND: Disturbances in evidence gathering and disconfirmatory evidence
      integration have been associated with the presence of or propensity for
      delusions. Previous evidence suggests that these 2 types of reasoning bias might
      be differentially affected by antipsychotic medication. We aimed to investigate
      the effects of a dopaminergic agonist (L-dopa) and a dopaminergic antagonist
      (haloperidol) on evidence gathering and disconfirmatory evidence integration
      after single-dose administration in healthy individuals. METHODS: The study used
      a randomized, double-blind, placebo-controlled, 3-way crossover design.
      Participants were healthy individuals aged 18-40 years. We administered a new
      data-gathering task designed to increase sensitivity to change compared with
      traditional tasks. The Bias Against Disconfirmatory Evidence (BADE) task was used
      as a measure of disconfirmatory evidence integration. RESULTS: We included 30
      individuals in our study. In the data-gathering task, dopaminergic modulation had
      no significant effect on the amount of evidence gathered before reaching a
      decision. In contrast, the ability of participants to integrate disconfirmatory
      evidence showed a significant linear dopaminergic modulation pattern (highest
      with haloperidol, intermediate with placebo, lowest with L-dopa), with the
      difference between haloperidol and L-dopa marginally reaching significance.
      LIMITATIONS: Although the doses used for haloperidol and L-dopa were similar to
      those used in previous studies, drug plasma level measurements would have added
      to the validity of findings. CONCLUSION: Evidence gathering and disconfirmatory
      evidence integration might be differentially influenced by dopaminergic agents.
      Our findings are in support of a dual-disturbance account of delusions and
      provide a plausible neurobiological basis for the use of interventions targeted
      at improving reasoning biases as an adjunctive treatment in patients with
      psychotic disorders.

PMID- 26197304
TI  - Cytosolic pressure provides a propulsive force comparable to actin polymerization
      during lamellipod protrusion.
AB  - Does cytosolic pressure facilitate f-actin polymerization to push the leading
      edge of a cell forward during self-propelled motion? AFM force-distance (f-d)
      curves obtained from lamellipodia of live cells often exhibit a signal from which
      the tension, bending modulus, elastic modulus and thickness in the membrane
      cortex complex can be estimated close to the contact point. These measurements
      permit an estimate of the cytosolic pressure via the canonical Laplace force
      balance. The deeper portion of the f-d curve allows estimation of the bulk
      modulus of the cytoskeleton after removal of the bottom effect artifact. These
      estimates of tension, pressure, cortex thickness and elastic moduli imply that
      cytosolic pressure both pushes the membrane forward and compresses the actin
      cortex rearward to facilitate f-actin polymerization. We also estimate that
      cytosolic pressure fluctuations, most likely induced by myosin, provide a
      propulsive force comparable to that provided by f-actin polymerization in a
      lamellipod. 

PMID- 26197305
TI  - The influence of the combination of carboxylate and phosphinate pendant arms in
      1,4,7-triazacyclononane-based chelators on their 68Ga labelling properties.
AB  - In order to compare the coordination properties of 1,4,7-triazacyclononane (tacn)
      derivatives bearing varying numbers of phosphinic/carboxylic acid pendant groups
      towards 68Ga, 1,4,7-triazacyclononane-7-acetic-1,4-bis(methylenephosphinic) acid
      (NOPA) and 1,4,7- triazacyclononane-4,7-diacetic-1-[methylene(2
      carboxyethyl)phosphinic] acid (NO2AP) were synthesized using Mannich reactions
      with trivalent or pentavalent forms of H-phosphinic acids as phosphorus
      components. Stepwise protonation constants logK1-3 12.06, 3.90 and 1.95, and
      stability constants with GaIII and CuII, logKGaL 24.01 and logKCuL 16.66, were
      potentiometrically determined for NOPA. Both ligands were labelled with 68Ga and
      compared with NOTA (tacn-N,N',N"-triacetic acid) and NOPO, a TRAP-type [tacn
      N,N',N"- tris(methylenephosphinic acid)] chelator. At pH 3, NOPO and NOPA showed
      higher labelling efficiency (binding with lower ligand excess) at both room
      temperature and 95  degrees C, compared to NO2AP and NOTA. Labelling efficiency
      at pH = 0-3 correlated with a number of phosphinic acid pendants: NOPO >> NOPA >
      NO2AP >> NOTA; however, it was more apparent at 95  degrees C than at room
      temperature. By contrast, NOTA was found to be labelled more efficiently at pH >
      4 compared to the ligands with phosphinic acids. Overall, replacement of a single
      phosphinate donor with a carboxylate does not challenge 68Ga labelling of TRAP
      type chelators. However, the presence of carboxylates facilitates labelling at
      neutral or weakly acidic pH. 

PMID- 26197306
TI  - A new furofuran lignan diglycoside and other secondary metabolites from the
      antidepressant extract of Castilleja tenuiflora Benth.
AB  - Castilleja tenuiflora has been used for the treatment of several Central Nervous
      System (CNS) diseases. Herein we report the antidepressant activity of the
      methanol extract from the leaves of this medicinal plant. The oral administration
      of MeOH extract (500 mg/kg) induced a significant (p < 0.05) decrement of the
      immobility parameter on Forced Swimming Test (FST) and an increment in the
      latency and duration of the hypnosis, induced by administration of sodium
      pentobarbital (Pbi, 40 mg/kg, i.p.). Chemical analysis of this antidepressant
      extract allowed the isolation of (+)-piperitol-4-O-xylopyranosyl-(1->6)-O
      glucopyranoside. This new furofuran lignan diglycoside was named tenuifloroside
      (1) and its complete chemical structure elucidation on the basis of 1D and 2D NMR
      spectra analysis of the natural compound 1 and its peracetylated derivative 1a is
      described. This compound was found together with two flavones-apigenin and
      luteolin 5-methyl ether-a phenylethanoid-verbascoside-and three iridoids
      geniposide, caryoptoside and aucubin. All these compounds were purified by
      successive normal and reverse phase column chromatography. Tenuifloroside,
      caryoptoside and luteolin 5-methyl ether were isolated from Castilleja genus for
      the first time. These findings demonstrate that C. tenuiflora methanol extract
      has beneficial effect on depressive behaviors, and the knowledge of its chemical
      constitution allows us to propose a new standardized treatment for future
      investigations of this species in depressive illness. 

PMID- 26197307
TI  - Allergenic proteins in enology: a review on technological applications and safety
      aspects.
AB  - Proteinaceous products are widely used as fining agents during winemaking to
      remove unwanted insoluble particles and undissolved microscopic particles
      (colloidal material) from the must or wine to improve stability. Some of them
      (egg white, caseinates, and fish gelatine) have allergenic potential and the
      presence of their residues in the final product could represent a risk for
      allergic individuals. Moreover, lysozyme (an egg allergen) is included among wine
      additives to control the fermentation processes and avoid spoiling during
      winemaking. The aim of this paper is to review the experimental/clinical data on
      the use of allergenic products in enology and the measurement of relative risk
      for sensitized subjects. In addition, methods developed specifically for the
      quantification of allergenic residues in must and wine are described. 

PMID- 26197308
TI  - Molecular docking and multivariate analysis of xanthones as antimicrobial and
      antiviral agents.
AB  - Xanthones are secondary metabolites which have drawn considerable interest over
      the last decades due to their antimicrobial properties, among others. A great
      number of this kind of compounds has been therefore reported, but there is a
      limited amount of studies on screening for biological activity. Thus, as part of
      our research on antimicrobial agents of natural origin, a set of 272 xanthones
      were submitted to molecular docking (MD) calculations with a group of seven
      fungal and two viral enzymes. The results indicated that prenylated xanthones are
      important hits for inhibition of the analyzed enzymes. The MD scores were also
      analyzed by multivariate statistics. Important structural details were found to
      be crucial for the inhibition of the tested enzymes by the xanthones. In
      addition, the classification of active xanthones can be achieved by statistical
      analysis on molecular docking scores by an affinity-antifungal activity
      relationship approach. The obtained results therefore are a suitable starting
      point for the development of antifungal and antiviral agents based on xanthones. 

PMID- 26197309
TI  - New cembranoid diterpenes from the cultured octocoral Nephthea columnaris.
AB  - Two new 15-hydroxycembranoid diterpenes, 2beta-hydroxy-7beta,8alpha
      epoxynephthenol (1) and 2beta-hydroxy-11alpha,12beta-epoxynephthenol (2), were
      isolated from extracts of the octocoral Nephthea columnaris along with a new
      natural cembrane, epoxynephthenol (3) and a known sterol, nephalsterol A (4). The
      structures of cembranes 1-3 were elucidated by spectroscopic methods and
      comparison of the spectroscopic data with those of related analogues. The
      cytotoxicity of metabolites 1-4 against a panel of tumor cells is also described.

PMID- 26197310
TI  - Separation of polyphenols and caffeine from the acetone extract of fermented tea
      leaves (Camellia sinensis) using high-performance countercurrent chromatography.
AB  - Leaves from Camellia sienensis are a popular natural source of various beverage
      worldwide, and contain caffeine and polyphenols derived from catechin analogues.
      In the current study, caffeine (CAF, 1) and three tea polyphenols including (-)
      epigallocatechin 3-O-gallate (EGCg, 2), (-)-gallocatechin 3-O-gallate (GCg, 3),
      and (-)-epicatechin 3-O-gallate (ECg, 4) were isolated and purified by flow-rate
      gradient high-performance countercurrent chromatography (HPCCC) using a two-phase
      solvent system composed of n-hexane-ethyl acetate-methanol-water (1:9:1:9, v/v).
      Two hundred milligrams of acetone-soluble extract from fermented C. sinensis
      leaves was separated by HPCCC to give 1 (25.4 mg), 2 (16.3 mg), 3 (11.1 mg) and 4
      (4.4 mg) with purities over 98%. The structures of 1-4 were elucidated by QTOF
      MS, as well as 1H- and 13C-NMR, and the obtained data were compared to the
      previously reported values. 

PMID- 26197311
TI  - The enhanced inhibitory effect of different antitumor agents in self
      microemulsifying drug delivery systems on human cervical cancer HeLa cells.
AB  - The aim of this study was to develop topical self-microemulsifying drug delivery
      systems (SMEDDS) containing antitumor agents (bleomycin, cisplatin and
      ifosfamide) and to investigate their inhibitory potential in SMEDDS on human
      cervical cancer HeLa cells. The physicochemical properties of cytostatic drug
      loaded SMEDDS were characterized. The cytotoxicity of main components of SMEDDS
      was also investigated. Their IC50 values were determined. HeLa cells were treated
      by different concentrations of cisplatin, bleomycin and ifosfamide alone and in
      various SMEDDS. The inhibitory effect on cell growth was analyzed by MTT cell
      viability assay. Inflammation is a driving force that accelerates cancer
      development. The inhibitory effect of these antitumor agents has also been tested
      on HeLa cells in the presence of inflammatory mediators (IL-1-beta, TNF-alpha) as
      an in vitro model of inflamed human cervix. Significant differences in the
      cytotoxicity of cytostatic drugs alone and in SMEDDS have been found in a
      concentration-dependent manner. The self-micro emulsifying system may potentiate
      the effectiveness of bleomycin, cisplatin and ifosfamide topically. The effect of
      SMEDDS containing antitumor agents was decreased significantly in the presence of
      inflammatory mediators. According to our experiments, the optimal SMEDDS
      formulation is 1:1:2:6:2 ratios of Isopropyl myristate, Capryol 90, Kolliphor RH
      40, Cremophor RH40, Transcutol HP and Labrasol. It can be concluded that SMEDDS
      may increase the inhibitory effect of bleomycin, ifosfamide and cisplatin on
      human cervical cancer HeLa cells. Inflammation on HeLa cells hinders the
      effectiveness of SMEDDS containing antitumor agents. Our results might ensure
      useful data for development of optimal antitumor formulations. 

PMID- 26197312
TI  - Synthesis, spectroscopic investigations (X-ray, NMR and TD-DFT), antimicrobial
      activity and molecular docking of 2,6-bis(hydroxy(phenyl)methyl)cyclohexanone.
AB  - The synthesis of 2,6-bis(hydroxy(phenyl)methyl)cyclohexanone 1 is described. The
      molecular structure of the title compound 1 was confirmed by NMR, FT-IR, MS, CHN
      microanalysis, and X-ray crystallography. The molecular structure was also
      investigated by a set of computational studies and found to be in good agreement
      with the experimental data obtained from the various spectrophotometric
      techniques. The antimicrobial activity and molecular docking of the synthesized
      compound was investigated. 

PMID- 26197313
TI  - Evaluation of the cytotoxicity of structurally correlated p-menthane derivatives.
AB  - Compounds isolated from essential oils play an important role in the prevention
      and treatment of cancer. Monoterpenes are natural products, and the principal
      constituents of many essential oils. The aim of this study was to investigate the
      cytotoxic potential of p-menthane derivatives. Additionally, analogues of
      perillyl alcohol, a monoterpene with known anticancer activity, were evaluated to
      identify the molecular characteristics which contribute to their cytotoxicity,
      which was tested against OVCAR-8, HCT-116, and SF-295 human tumor cell lines,
      using the MTT assay. The results of this study showed that (-)-perillaldehyde 8,9
      epoxide exhibited the highest percentage inhibition of cell proliferation (GI =
      96.32%-99.89%). Perillyl alcohol exhibited high cytotoxic activity (90.92%
      95.82%), while (+)-limonene 1,2-epoxide (GI = 58.48%-93.10%), (-)-perillaldehyde
      (GI = 59.28%-83.03%), and (-)-8-hydroxycarvotanacetone (GI = 61.59%-94.01%)
      showed intermediate activity. All of the compounds tested were less cytotoxic
      than perillyl alcohol, except (-)-perillaldehyde 8,9-epoxide (IC50 = 1.75-1.03
      uL/mg). In general, replacement of C-C double bonds by epoxide groups in addition
      to the aldehyde group increases cytotoxicity. Furthermore, stereochemistry seems
      to play an important role in cytotoxicity. We have demonstrated the cytotoxic
      influence of chemical substituents on the p-menthane structure, and analogues of
      perillyl alcohol. 

PMID- 26197314
TI  - Morphogenesis, Flowering, and Gene Expression of Dendranthema grandiflorum in
      Response to Shift in Light Quality of Night Interruption.
AB  - The impact of shifts in the spectral quality of light on morphogenesis,
      flowering, and photoperiodic gene expression during exposure to light quality of
      night interruption (NI) was investigated in Dendranthema grandiflorum. The
      circadian rhythms of plants grown in a closed walk-in growth chamber were
      interrupted at night for a total of 4 h, using light-emitting diodes with an
      intensity of 10 MUmol.m-2.s-1 PPF. The light quality of the NI was shifted from
      one wavelength to another after the first 2 h. Light treatments consisting of all
      possible pairings of blue (B), red (R), far-red (Fr), and white (W) light were
      tested. Plants in the NI treatment groups exposed to Fr light grew larger than
      plants in other treatment groups. Of plants in NI treatment groups, those in the
      NI-WB treatment grew the least. In addition, the impact of shifts in the light
      quality of NI on leaf expansion was greater in treatment groups exposed to a
      combination of either B and R or R and W light, regardless of their order of
      supply. Flowering was observed in the NI-RB, NI-FrR, NI-BFr, NI-FrB, NI-WB, NI
      FrW, NI-WFr, NI-WR, and SD (short-day) treatments, and was especially promoted in
      the NI-BFr and NI-FrB treatments. In a combined shift treatment of B and R or B
      and W light, the NI concluded with B light (NI-RB and NI-WB) treatment induced
      flowering. The transcriptional factors phyA, cry1 and FTL (FLOWERING LOCUS T)
      were positively affected, while phyB and AFT were negatively affected. In
      conclusion, morphogenesis, flowering, and transcriptional factors were all
      significantly affected either positively or negatively by shifts in the light
      quality of NI. The light quality of the first 2 h of NI affected neither
      morphogenesis nor flowering, while the light quality of the last 2 h of NI
      significantly affected both morphogenesis and flowering.

PMID- 26197315
TI  - Sleep Disorders Reduce Health-Related Quality of Life in Multiple Sclerosis
      (Nottingham Health Profile Data in Patients with Multiple Sclerosis).
AB  - Quality of Life (QoL) is decreased in multiple sclerosis (MS), but studies about
      the impact of sleep disorders (SD) on health-related quality of Life (HRQoL) are
      lacking. From our original cohort, a cross-sectional polysomnographic (PSG) study
      in consecutive MS patients, we retrospectively analysed the previously
      unpublished data of the Nottingham Health Profile (NHP). Those MS patients
      suffering from sleep disorders (n = 49) showed significantly lower HRQoL compared
      to MS patients without sleep disorders (n = 17). Subsequently, we classified the
      patients into four subgroups: insomnia (n = 17), restless-legs syndrome, periodic
      limb movement disorder and SD due to leg pain (n = 24), obstructive sleep apnea
      (n = 8) and patients without sleep disorder (n = 17). OSA and insomnia patients
      showed significantly higher NHP values and decreased HRQoL not only for the sleep
      subscale but also for the "energy" and "emotional" area of the NHP. In addition,
      OSA patients also showed increased NHP values in the "physical abilities" area.
      Interestingly, we did not find a correlation between the objective PSG parameters
      and the subjective sleep items of the NHP. However, this study demonstrates that
      sleep disorders can reduce HRQoL in MS patients and should be considered as an
      important confounder in all studies investigating HRQoL in MS. 

PMID- 26197316
TI  - Differential Antioxidant Responses and Perturbed Porphyrin Biosynthesis after
      Exposure to Oxyfluorfen and Methyl Viologen in Oryza sativa.
AB  - We compared antioxidant responses and regulation of porphyrin metabolism in rice
      plants treated with oxyfluorfen (OF) or methyl viologen (MV). Plants treated with
      MV exhibited not only greater increases in conductivity and malondialdehyde but
      also a greater decline in Fv/Fm, compared to plants treated with OF. MV-treated
      plants had greater increases in activities of superoxide dismutase (SOD) and
      catalase (CAT) as well as transcript levels of SODA and CATA than OF-treated
      plants after 28 h of the treatments, whereas increases in ascorbate peroxidase
      (APX) activity and transcript levels of APXA and APXB were greater in OF-treated
      plants. Both OF- and MV-treated plants resulted in not only down-regulation of
      most genes involved in porphyrin biosynthesis but also disappearance of Mg
      porphyrins during the late stage of photooxidative stress. By contrast, up
      regulation of heme oxygenase 2 (HO2) is possibly part of an efficient antioxidant
      response to compensate photooxidative damage in both treatments. Our data show
      that down-regulated biosynthesis and degradation dynamics of porphyrin
      intermediates have important roles in photoprotection of plants from perturbed
      porphyrin biosynthesis and photosynthetic electron transport. This study suggests
      that porphyrin scavenging as well as strong antioxidative activities are required
      for mitigating reactive oxygen species (ROS) production under photooxidative
      stress caused by OF and MV. 

PMID- 26197317
TI  - High Genetic Diversity of Microbial Cellulase and Hemicellulase Genes in the
      Hindgut of Holotrichia parallela Larvae.
AB  - In this study, we used a culture-independent method based on library construction
      and sequencing to analyze the genetic diversity of the cellulase and
      hemicellulase genes of the bacterial community resident in the hindgut of
      Holotrichia parallela larvae. The results indicate that there is a large, diverse
      set of bacterial genes encoding lignocellulose hydrolysis enzymes in the hindgut
      of H. parallela. The total of 101 distinct gene fragments (similarity <95%) of
      glycosyl hydrolase families including GH2 (24 genes), GH8 (27 genes), GH10 (19
      genes), GH11 (14 genes) and GH36 (17 genes) families was retrieved, and certain
      sequences of GH2 (10.61%), GH8 (3.33%), and GH11 (18.42%) families had <60%
      identities with known sequences in GenBank, indicating their novelty. Based on
      phylogenetic analysis, sequences from hemicellulase families were related to
      enzymes from Bacteroidetes and Firmicutes. Fragments from cellulase family were
      most associated with the phylum of Proteobacteria. Furthermore, a full-length
      endo-xylanase gene was obtained, and the enzyme exhibited activity over a broad
      range of pH levels. Our results indicate that there are large number of
      cellulolytic and xylanolytic bacteria in the hindgut of H. parallela larvae, and
      these symbiotic bacteria play an important role in the degradation of roots and
      other organic matter for the host insect. 

PMID- 26197318
TI  - NOS1AP O-GlcNAc Modification Involved in Neuron Apoptosis Induced by
      Excitotoxicity.
AB  - O-Linked N-acetylglucosamine, or O-GlcNAc, is a dynamic post-translational
      modification that cycles on and off serine and threonine residues of
      nucleocytoplasmic and mitochondrial proteins. In addition to cancer and
      inflammation diseases, O-GlcNAc modification appears to play a critical role
      during cell apoptosis and stress response, although the precise mechanisms are
      still not very clear. Here we found that nitric oxide synthase adaptor (NOS1AP),
      which plays an important part in glutamate-induced neuronal apoptosis, carries
      the modification of O-GlcNAc. Mass spectrometry analysis identified Ser47,
      Ser183, Ser204, Ser269, Ser271 as O-GlcNAc sites. Higher O-GlcNAc of NOS1AP was
      detected during glutamate-induced neuronal apoptosis. Furthermore, with O-GlcNAc
      sites of NOS1AP mutated, the interaction of NOS1AP and neuronal nitric oxide
      syntheses (nNOS) decreases. Finally, during glutamate-induced neuronal apoptosis,
      decreasing the O-GlcNAc modification of NOS1AP results in more severe neuronal
      apoptosis. All these results suggest that O-GlcNAc modification of NOS1AP exerts
      protective effects during glutamate-induced neuronal apoptosis. 

PMID- 26197320
TI  - Multiscale Trend Analysis for Pampa Grasslands Using Ground Data and Vegetation
      Sensor Imagery.
AB  - This study aimed to evaluate changes in the aboveground net primary productivity
      (ANPP) of grasslands in the Pampa biome by using experimental plots and changes
      in the spectral responses of similar vegetation communities obtained by remote
      sensing and to compare both datasets with meteorological variations to validate
      the transition scales of the datasets. Two different geographic scales were
      considered in this study. At the local scale, an analysis of the climate and its
      direct influences on grassland ANPP was performed using data from a long-term
      experiment. At the regional scale, the influences of climate on the grassland
      reflectance patterns were determined using vegetation sensor imagery data.
      Overall, the monthly variations of vegetation canopy growth analysed using
      environmental changes (air temperature, total rainfall and total
      evapotranspiration) were similar. The results from the ANPP data and the NDVI
      data showed the that variations in grassland growth were similar and independent
      of the analysis scale, which indicated that local data and the relationships of
      local data with climate can be considered at the regional scale in the Pampa
      biome by using remote sensing. 

PMID- 26197319
TI  - B Cells and Autoantibodies in Multiple Sclerosis.
AB  - While over the past decades T cells have been considered key players in the
      pathogenesis of multiple sclerosis (MS), it has only recently become evident that
      B cells have a major contributing role. Our understanding of the role of B cells
      has evolved substantially following the clinical success of B cell-targeting
      therapies and increasing experimental evidence for significant B cell
      involvement. Rather than mere antibody-producing cells, it is becoming clear that
      they are team players with the capacity to prime and regulate T cells, and
      function both as pro- and anti-inflammatory mediators. However, despite
      tremendous efforts, the target antigen(s) of B cells in MS have yet to be
      identified. The first part of this review summarizes the clinical evidence and
      results from animal studies pointing to the relevance of B cells in the
      pathogenesis of MS. The second part gives an overview of the currently known
      potential autoantigen targets. The third part recapitulates and critically
      appraises the currently available B cell-directed therapies. 

PMID- 26197321
TI  - Fast T Wave Detection Calibrated by Clinical Knowledge with Annotation of P and T
      Waves.
AB  - BACKGROUND: There are limited studies on the automatic detection of T waves in
      arrhythmic electrocardiogram (ECG) signals. This is perhaps because there is no
      available arrhythmia dataset with annotated T waves. There is a growing need to
      develop numerically-efficient algorithms that can accommodate the new trend of
      battery-driven ECG devices. Moreover, there is also a need to analyze long-term
      recorded signals in a reliable and time-efficient manner, therefore improving the
      diagnostic ability of mobile devices and point-of-care technologies. METHODS:
      Here, the T wave annotation of the well-known MIT-BIH arrhythmia database is
      discussed and provided. Moreover, a simple fast method for detecting T waves is
      introduced. A typical T wave detection method has been reduced to a basic
      approach consisting of two moving averages and dynamic thresholds. The dynamic
      thresholds were calibrated using four clinically known types of sinus node
      response to atrial premature depolarization (compensation, reset, interpolation,
      and reentry). RESULTS: The determination of T wave peaks is performed and the
      proposed algorithm is evaluated on two well-known databases, the QT and MIT-BIH
      Arrhythmia databases. The detector obtained a sensitivity of 97.14% and a
      positive predictivity of 99.29% over the first lead of the validation databases
      (total of 221,186 beats). CONCLUSIONS: We present a simple yet very reliable T
      wave detection algorithm that can be potentially implemented on mobile battery
      driven devices. In contrast to complex methods, it can be easily implemented in a
      digital filter design.

PMID- 26197322
TI  - Electrochemical Impedance Sensors for Monitoring Trace Amounts of NO3 in Selected
      Growing Media.
AB  - With the advent of smart cities and big data, precision agriculture allows the
      feeding of sensor data into online databases for continuous crop monitoring,
      production optimization, and data storage. This paper describes a low-cost,
      compact, and scalable nitrate sensor based on electrochemical impedance
      spectroscopy for monitoring trace amounts of NO3- in selected growing media. The
      nitrate sensor can be integrated to conventional microelectronics to perform
      online nitrate sensing continuously over a wide concentration range from 0.1 ppm
      to 100 ppm, with a response time of about 1 min, and feed data into a database
      for storage and analysis. The paper describes the structural design, the Nyquist
      impedance response, the measurement sensitivity and accuracy, and the field
      testing of the nitrate sensor performed within tree nursery settings under
      ISO/IEC 17025 certifications. 

PMID- 26197323
TI  - Processing and Characterization of a Novel Distributed Strain Sensor Using Carbon
      Nanotube-Based Nonwoven Composites.
AB  - This paper describes the development of an innovative carbon nanotube-based non
      woven composite sensor that can be tailored for strain sensing properties and
      potentially offers a reliable and cost-effective sensing option for structural
      health monitoring (SHM). This novel strain sensor is fabricated using a readily
      scalable process of coating Carbon nanotubes (CNT) onto a nonwoven carrier fabric
      to form an electrically-isotropic conductive network. Epoxy is then infused into
      the CNT-modified fabric to form a free-standing nanocomposite strain sensor. By
      measuring the changes in the electrical properties of the sensing composite the
      deformation can be measured in real-time. The sensors are repeatable and linear
      up to 0.4% strain. Highest elastic strain gage factors of 1.9 and 4.0 have been
      achieved in the longitudinal and transverse direction, respectively. Although the
      longitudinal gage factor of the newly formed nanocomposite sensor is close to
      some metallic foil strain gages, the proposed sensing methodology offers spatial
      coverage, manufacturing customizability, distributed sensing capability as well
      as transverse sensitivity. 

PMID- 26197324
TI  - Novel Method for Processing the Dynamic Calibration Signal of Pressure Sensor.
AB  - Dynamic calibration is one of the important ways to acquire the dynamic
      performance parameters of a pressure sensor. This research focuses on the
      processing method for the output of calibrated pressure sensor, and mainly
      attempts to solve the problem of extracting the true information of step response
      under strong interference noise. A dynamic calibration system based on a shock
      tube is established to excite the time-domain response signal of a calibrated
      pressure sensor. A key processing on difference modeling is applied for the
      obtained signal, and several generating sequences are established. A fusion
      process for the generating sequences is then undertaken, and the true information
      of the step response of the calibrated pressure sensor can be obtained. Finally,
      by implementing the common QR decomposition method to deal with the true
      information, a dynamic model characterizing the dynamic performance of the
      calibrated pressure sensor is established. A typical pressure sensor was used to
      perform calibration tests and a frequency-domain experiment for the sensor was
      also conducted. Results show that the proposed method could effectively filter
      strong interference noise in the output of the sensor and the corresponding
      dynamic model could effectively characterize the dynamic performance of the
      pressure sensor. 

PMID- 26197325
TI  - Evaluation of Potential Thrombin Inhibitors from the White Mangrove (Laguncularia
      racemosa (L.) C.F. Gaertn.).
AB  - The aim of this work was to verify the effects of methanol (MeOH) and
      hydroalcoholic (HA) extracts and their respective partition phases obtained from
      white mangrove (Laguncularia racemosa (L.) C.F. Gaertn.) leaves on human thrombin
      activity. Among the extracts and phases tested, only the ethyl acetate and
      butanolic partitions significantly inhibited human thrombin activity and the
      coagulation of plasma in the presence of this enzyme. Chromatographic analyses of
      the thrombin samples incubated with these phases revealed that different
      compounds were able to interact with thrombin. The butanolic phase of the MeOH
      extract had the most potent inhibitory effects, reducing enzymatic activity and
      thrombin-induced plasma coagulation. Two glycosylated flavonoids in this
      partition were identified as the most potent inhibitors of human thrombin
      activity, namely quercetin-3-O-arabinoside (QAra) and quercetin-3-O-rhamnoside
      (Qn). Chromatographic analyses of thrombin samples incubated with these
      flavonoids demonstrated the chemical modification of this enzyme, suggesting that
      the MeOH extract contained other compounds that both induced structural changes
      in thrombin and diminished its activity. In this article, we show that despite
      the near absence of the medical use of mangrove compounds, this plant contains
      natural compounds with potential therapeutic applications. 

PMID- 26197326
TI  - A Simulated Environment Experiment on Annoyance Due to Combined Road Traffic and
      Industrial Noises.
AB  - Total annoyance due to combined noises is still difficult to predict adequately.
      This scientific gap is an obstacle for noise action planning, especially in urban
      areas where inhabitants are usually exposed to high noise levels from multiple
      sources. In this context, this work aims to highlight potential to enhance the
      prediction of total annoyance. The work is based on a simulated environment
      experiment where participants performed activities in a living room while exposed
      to combined road traffic and industrial noises. The first objective of the
      experiment presented in this paper was to gain further understanding of the
      effects on annoyance of some acoustical factors, non-acoustical factors and
      potential interactions between the combined noise sources. The second one was to
      assess total annoyance models constructed from the data collected during the
      experiment and tested using data gathered in situ. The results obtained in this
      work highlighted the superiority of perceptual models. In particular, perceptual
      models with an interaction term seemed to be the best predictors for the two
      combined noise sources under study, even with high differences in sound pressure
      level. Thus, these results reinforced the need to focus on perceptual models and
      to improve the prediction of partial annoyances. 

PMID- 26197327
TI  - Metabolic Polymorphisms and Clinical Findings Related to Benzene Poisoning
      Detected in Exposed Brazilian Gas-Station Workers.
AB  - Benzene is a ubiquitous environmental pollutant and an important industrial
      chemical present in both gasoline and motor vehicle emissions. Occupational human
      exposure to benzene occurs in the petrochemical and petroleum refining industries
      as well as in gas-station workers, where it can lead to benzene poisoning (BP),
      but the mechanisms of BP are not completely understood. In Brazil, a significant
      number of gas-station service workers are employed. The aim of the present study
      was to evaluate alterations related to BP and metabolic polymorphisms in gas
      station service workers exposed to benzene in the city of Rio de Janeiro, Brazil.
      Occupational exposure was based on clinical findings related to BP, and metabolic
      polymorphisms in 114 Brazilian gas-station attendants. These workers were divided
      into No Clinical Findings (NCF) and Clinical Findings (CF) groups. Neutrophil and
      Mean Corpuscular Volume (MCV) showed a significant difference between the two
      study groups, and neutrophil has the greatest impact on the alterations
      suggestive of BP. The clinical findings revealed higher frequencies of symptoms
      in the CF group, although not all members presented statistical significance. The
      frequencies of alleles related to risk were higher in the CF group for GSTM1,
      GSTT1, CYP2E1 7632T > A, but lower for NQO1 and CYP2E1 1053C > T genotypes.
      Moreover, an association was found between GSTM1 null and alterations related to
      BP, but we did not observe any effects of other polymorphisms. Variations in
      benzene metabolizing genes may modify benzene toxicity and should be taken into
      consideration during risk assessment evaluations. 

PMID- 26197329
TI  - Occupant Interactions and Effectiveness of Natural Ventilation Strategies in
      Contemporary New Housing in Scotland, UK.
AB  - The need to reduce carbon emissions and fuel poverty has led to increased
      building envelope air tightness, intended to reduce uncontrolled ventilation heat
      losses. Ventilation strategies in dwellings still allow the use of trickle
      ventilators in window frames for background ventilation. The extent to which this
      results in "healthy" Indoor Air Quality (IAQ) in recently constructed dwellings
      was a concern of regulators in Scotland. This paper describes research to explore
      this. First a review of literature was conducted, then data on occupant
      interactions with ventilation provisions (windows, doors, trickle vents) gathered
      through an interview-based survey of 200 recently constructed dwellings, and
      measurements made on a sample of 40 of these. The main measured parameter
      discussed here is CO2 concentration. It was concluded after the literature review
      that 1000 ppm absolute was a reasonable threshold to use for "adequate"
      ventilation. The occupant survey found that there was very little occupant
      interaction with the trickle ventilators e.g., in bedrooms 63% were always
      closed, 28% always open, and in only 9% of cases occupants intervened to make
      occasional adjustments. In the measured dwellings average bedroom CO2 levels of
      1520 ppm during occupied (night time) hours were observed. Where windows were
      open the average bedroom CO2 levels were 972 ppm. With windows closed, the
      combination of "trickle ventilators open plus doors open" gave an average of 1021
      ppm. "Trickle ventilators open" gave an average of 1571 ppm. All other
      combinations gave averages of 1550 to 2000 ppm. Ventilation rates and air change
      rates were estimated from measured CO2 levels, for all dwellings calculated
      ventilation rate was less than 8 L/s/p, in 42% of cases calculated air change
      rate was less than 0.5 ach. It was concluded that trickle ventilation as
      installed and used is ineffective in meeting desired ventilation rates, evidenced
      by high CO2 levels reported across the sampled dwellings. Potential implications
      of the results are discussed. 

PMID- 26197328
TI  - Evaluating the Long-Term Health and Economic Impacts of Central Residential Air
      Filtration for Reducing Premature Mortality Associated with Indoor Fine
      Particulate Matter (PM2.5) of Outdoor Origin.
AB  - Much of human exposure to fine particulate matter (PM2.5) of outdoor origin
      occurs in residences. High-efficiency particle air filtration in central heating,
      ventilating, and air-conditioning (HVAC) systems is increasingly being used to
      reduce concentrations of particulate matter inside homes. However, questions
      remain about the effectiveness of filtration for reducing exposures to PM2.5 of
      outdoor origin and adverse health outcomes. Here we integrate epidemiology
      functions and mass balance modeling to estimate the long-term health and economic
      impacts of HVAC filtration for reducing premature mortality associated with
      indoor PM2.5 of outdoor origin in residences. We evaluate 11 classifications of
      filters (MERV 5 through HEPA) using six case studies of single-family home
      vintages and ventilation system combinations located in 22 U.S. cities. We
      estimate that widespread use of higher efficiency filters would reduce premature
      mortality by 0.002-2.5% and increase life expectancy by 0.02-1.6 months, yielding
      annual monetary benefits ranging from $1 to $1348 per person in the homes and
      locations modeled herein. Large differences in the magnitude of health and
      economic impacts are driven largely by differences in rated filter efficiency and
      building and ventilation system characteristics that govern particle infiltration
      and persistence, with smaller influences attributable to geographic location. 

PMID- 26197330
TI  - Managing Groundwater Radioactive Contamination at the Daiichi Nuclear Plant.
AB  - The Great East Japan Earthquake and tsunami of March 2011 severely damaged three
      reactors at the Fukushima Daiichi nuclear power station, leading to a major
      release of radiation into the environment. Groundwater flow through these
      crippled reactors continues to be one of the main causes of contamination and
      associated transport of radionuclides into the Pacific Ocean. In this context, a
      number of strategies are being implemented to manage radioactive pollution of the
      water resources at the nuclear plant site. Along with water treatment and
      purification, it is critical to restrict the groundwater flow to and from the
      reactors. Thus, the devised strategies combine walls containment, bores
      abstraction, infiltration control, and the use of tanks for the temporary storage
      of contaminated waters. While some of these techniques have been previously
      applied in other environments, they have never been tested at such a large scale.
      Therefore, their effectiveness remains to be seen. The present manuscript
      presents an overview of the methods being currently implemented to manage
      groundwater contamination and to mitigate the impact of hydrological pathways in
      the dispersion of radionuclides at Fukushima. 

PMID- 26197331
TI  - Defining Neighbourhoods as a Measure of Exposure to the Food Environment.
AB  - Neighbourhoods are frequently used as a measure for individuals' exposure to the
      food environment. However, the definitions of neighbourhoods fluctuate and have
      not been applied consistently in previous studies. Neighbourhoods defined from a
      single fixed location fail to capture people's complete exposure in multiple
      locations, but measuring behaviour using traditional methods can be challenging.
      This study compares the traditional methods of measuring exposure to the food
      environment to methods that use data from GPS tracking. For each of the 187
      participants, 11 different neighbourhoods were created in which the exposure to
      supermarkets and fast food outlets were measured. ANOVA, Tukey's Honestly
      Significant Difference (HSD) test and t-tests were performed to compare the
      neighbourhoods. Significant differences were found between area sizes and the
      exposure to supermarkets and fast food outlets for different neighbourhood types.
      Second, significant differences in exposure to food outlets were found between
      the urban and rural neighbourhoods. Neighbourhoods are clearly a diffused and
      blurred concept that varies in meaning depending on each person's perception and
      the conducted study. Complexity and heterogeneity of human mobility no longer
      appear to correspond to the use of residential neighbourhoods but rather
      emphasise the need for methods, concepts and measures of individual activity and
      exposure. 

PMID- 26197332
TI  - The Pattern of Variation between Diarrhea and Malaria Coexistence with
      Corresponding Risk Factors in, Chikhwawa, Malawi: A Bivariate Multilevel
      Analysis.
AB  - Developing countries face a huge burden of infectious diseases, a number of which
      co-exist. This paper estimates the pattern and variation of malaria and diarrhea
      coexistence in Chikhwawa, a district in Southern Malawi using bivariate
      multilevel modelling with Bayesian estimation. A probit link was employed to
      examine hierarchically built data from a survey of individuals (n = 6,727) nested
      within households (n = 1,380) nested within communities (n = 33). Results show
      significant malaria [sigma2MU1=0.901 (95% CI:0.746,1.056)] and diarrhea
      [sigma2MU2=1.009 (95% CI:0.860,1.158)] variations with a strong correlation
      between them [r(1,2)MU=0.565] at household level. There are significant malaria
      [sigma2nu1=0.053 (95% CI: 0.018,0.088)] and diarrhea [sigma2nu2=0.099(95% CI :
      0.030,0.168) ] variations at community level but with a small correlation [r(1,2)
      nu=0.124] between them. There is also significant correlation between malaria and
      diarrhea at individual level [ r(1,2) e=0.241]. These results suggest a close
      association between reported malaria-like illness and diarrheal illness
      especially at household and individual levels in Southern Malawi.

PMID- 26197333
TI  - Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly
      Curved Liposomes.
AB  - Dengue virus (DENV) is an important human pathogen causing millions of disease
      cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A) is a
      vital component of the viral replication complex (RC) and plays a major role in
      the formation of host cell membrane-derived structures that provide a scaffold
      for replication. The N-terminal cytoplasmic region of NS4A(1-48) is known to
      preferentially interact with highly curved membranes. Here, we provide
      experimental evidence for the stable binding of NS4A(1-48) to small liposomes
      using a liposome floatation assay and identify the lipid binding sequence by NMR
      spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV
      replication and to interfere with the binding of NS4A(1-48) to small liposomes.
      Our results provide new details on the interaction of the N-terminal region of
      NS4A with membranes and will prompt studies of the functional relevance of the
      curvature sensitive membrane anchor at the N-terminus of NS4A. 

PMID- 26197334
TI  - Serum Concentrations of Trace Elements in Patients with Tuberculosis and Its
      Association with Treatment Outcome.
AB  - Deficiencies in essential trace elements are associated with impaired immunity in
      tuberculosis infection. However, the trace element concentrations in the serum of
      Korean patients with tuberculosis have not yet been investigated. This study
      aimed to compare the serum trace element concentrations of Korean adult patients
      with tuberculosis with noninfected controls and to assess the impact of serum
      trace element concentration on clinical outcome after antituberculosis treatment.
      The serum concentrations of four trace elements in 141 consecutively recruited
      patients with tuberculosis and 79 controls were analyzed by inductively coupled
      plasma-mass spectrometry. Demographic characteristics were also analyzed. Serum
      cobalt and copper concentrations were significantly higher in patients with
      tuberculosis compared with controls, while zinc and selenium concentrations were
      significantly lower (p < 0.01). Moreover, serum selenium and zinc concentrations
      were positively correlated (rho = 0.41, p < 0.05). A high serum copper
      concentration was associated with a worse clinical outcome, as assessed after one
      month of antituberculosis therapy. Specifically, culture-positive patients had
      higher serum copper concentrations than culture-negative patients (p < 0.05).
      Patients with tuberculosis had altered serum trace element concentrations.
      Further research is needed to elucidate the roles of individual trace elements
      and to determine their clinical impact on patients with tuberculosis. 

PMID- 26197335
TI  - Reasons Low-Income Parents Offer Snacks to Children: How Feeding Rationale
      Influences Snack Frequency and Adherence to Dietary Recommendations.
AB  - Although American children snack more than ever before, the parental role in
      promoting snacking is not well understood. In 2012-2013 at baseline in an
      intervention study to prevent childhood obesity in low-income Massachusetts
      communities, n = 271 parents of children aged 2-12 years completed surveys
      regarding nutritive and non-nutritive reasons they offered children snacks,
      demographics, and dietary factors. An analysis of variance demonstrated that
      parents reported offering snacks (mean/week; standard deviation (SD)) for
      nutritive reasons like promoting growth (x = 2.5; SD 2.2) or satisfying hunger (x
      = 2.4; SD 2.1) almost twice as often as non-nutritive reasons like keeping a
      child quiet (x = 0.7; SD 1.5) or celebrating events/holidays (x = 0.8; SD 1.1).
      Parents reported giving young children (2-5 years) more snacks to reward behavior
      (1.9 vs. 1.1, p < 0.001), keep quiet (1.0 vs. 0.5, p < 0.001), and celebrate
      achievements (1.7 vs. 1.0, p < 0.001) than parents of older children (6-12
      years). Multivariable logistic regression models were used to obtain adjusted
      odds ratios, which indicated reduced child adherence to dietary recommendations
      when parents offered snacks to reward behavior (Odds Ratio (OR) = 0.83; 95%
      Confidence Interval (CI) 0.70-0.99), celebrate events/holidays (OR = 0.72; 95% CI
      0.52-0.99), or achievements (OR = 0.82; 95% CI 0.68-0.98). Parental intentions
      around child snacking are likely important targets for obesity prevention
      efforts. 

PMID- 26197336
TI  - Self-Reported Prevalence of Symptomatic Adverse Reactions to Gluten and Adherence
      to Gluten-Free Diet in an Adult Mexican Population.
AB  - The prevalence of symptomatic adverse reactions to gluten and adherence to gluten
      free diet in Latin American countries is unknown. These measurements are strongly
      linked to gluten-related disorders. This work aimed to estimate the prevalence of
      adverse reactions to oral gluten and the adherence to gluten-free diet in the
      adult Mexican population. To reach this aim, a self-administered questionnaire
      was designed and tested for clarity/comprehension and reproducibility. Then, a
      self-administered questionnaire-based cross-sectional study was conducted in the
      Mexican population. The estimated prevalence rates were (95% CI): 11.9% (9.9
      13.5) and 7.8 (6.4-9.4) for adverse and recurrent adverse reactions to gluten
      respectively; adherence to gluten-free diet 3.7% (2.7-4.8), wheat allergy 0.72%
      (0.38-1.37); celiac disease 0.08% (0.01-0.45), and NCGS 0.97% (0.55-1.68).
      Estimated pooled prevalence of self-reported physician-diagnosis of gluten
      related disorders was 0.88% (0.49-1.5), and 93.3% respondents reported adherence
      to gluten-free diet without a physician-diagnosis of gluten-related disorders.
      Symptom comparisons between those who reported recurrent adverse reactions to
      gluten and other foods showed statistically significant differences for bloating,
      constipation, and tiredness (p < 0.05). Gluten-related disorders may be
      underdiagnosed in the Mexican population and most people adhering to a gluten
      free diet are doing it without proper diagnostic work-up of these disorders, and
      probably without medical/dietician advice. 

PMID- 26197337
TI  - Increased Intake of Foods with High Nutrient Density Can Help to Break the
      Intergenerational Cycle of Malnutrition and Obesity.
AB  - A workshop held at the University Medical Center in Groningen, The Netherlands,
      aimed at discussing the nutritional situation of the population in general and
      the role diet plays during critical windows in the life course, during which the
      body is programmed for the development of non-communicable diseases (NCDs). NCDs
      are increasingly prevalent as our society ages, and nutrition is well known to
      play an important role in determining the risk and the time of onset of many
      common NCDs. Even in affluent countries, people have difficulties to achieve
      adequate intakes for a range of nutrients: Economic constraints as well as modern
      lifestyles lead people to consume diets with a positive energy balance, but low
      in micronutrients, resulting in increasing prevalence of obesity and suboptimal
      nutritional status. Information about nutrient density, which refers to the
      content of micronutrients relative to energy in food or diets, can help identify
      foods that have a low calorie to nutrient ratio. It thus allows the consumption
      of diets that cover nutritional needs without increasing the risk of becoming
      obese. Given the impact a nutrient dense, low energy diet can have on health,
      researchers, food industry and governments jointly should develop options for
      affordable, appealing nutrient-rich food products, which, in combination with
      physical activity, allow for optimal health throughout the life-course. 

PMID- 26197338
TI  - Biochemical Characterization of a Recombinant UDP-glucosyltransferase from Rice
      and Enzymatic Production of Deoxynivalenol-3-O-beta-D-glucoside.
AB  - Glycosylation is an important plant defense mechanism and conjugates of Fusarium
      mycotoxins often co-occur with their parent compounds in cereal-based food and
      feed. In case of deoxynivalenol (DON), deoxynivalenol-3-O-beta-D-glucoside (D3G)
      is the most important masked mycotoxin. The toxicological significance of D3G is
      not yet fully understood so that it is crucial to obtain this compound in pure
      and sufficient quantities for toxicological risk assessment and for use as an
      analytical standard. The aim of this study was the biochemical characterization
      of a DON-inactivating UDP-glucosyltransferase from rice (OsUGT79) and to
      investigate its suitability for preparative D3G synthesis. Apparent Michaelis
      constants (Km) of recombinant OsUGT79 were 0.23 mM DON and 2.2 mM UDP-glucose.
      Substrate inhibition occurred at DON concentrations above 2 mM (Ki = 24 mM DON),
      and UDP strongly inhibited the enzyme. Cu2+ and Zn2+ (1 mM) inhibited the enzyme
      completely. Sucrose synthase AtSUS1 was employed to regenerate UDP-glucose during
      the glucosylation reaction. With this approach, optimal conversion rates can be
      obtained at limited concentrations of the costly co-factor UDP-glucose. D3G can
      now be synthesized in sufficient quantity and purity. Similar strategies may be
      of interest to produce beta-glucosides of other toxins. 

PMID- 26197340
TI  - T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and
      Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion
      Molecules.
AB  - T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored member of the
      cadherin superfamily involved in the guidance of migrating cells. We have
      previously shown that in vivo T-cadherin overexpression leads to increased
      melanoma primary tumor growth due to the recruitment of mesenchymal stromal cells
      as well as the enhanced metastasis. Since tumor progression is highly dependent
      upon cell migration and invasion, the aim of the present study was to elucidate
      the mechanisms of T-cadherin participation in these processes. Herein we show
      that T-cadherin expression results in the increased invasive potential due to the
      upregulated expression of pro-oncogenic integrins, chemokines, adhesion molecules
      and extracellular matrix components. The detected increase in chemokine
      expression could be responsible for the stromal cell recruitment. At the same
      time our previous data demonstrated that T-cadherin expression inhibited
      neoangiogenesis in the primary tumors. We demonstrate molecules and reduction in
      pro-angiogenic factors. Thus, T-cadherin plays a dual role in melanoma growth and
      progression: T-cadherin expression results in anti-angiogenic effects in
      melanoma, however, this also stimulates transcription of genes responsible for
      migration and invasion of melanoma cells. 

PMID- 26197339
TI  - The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human
      Cancer.
AB  - Defined cellular mechanisms have evolved that recognize and repair DNA to protect
      the integrity of its structure and sequence when encountering assaults from
      endogenous and exogenous sources. There are five major DNA repair pathways:
      mismatch repair, nucleotide excision repair, direct repair, base excision repair
      and DNA double strand break repair (including non-homologous end joining and
      homologous recombination repair). Aberrant activation of the Hedgehog (Hh)
      signaling pathway is a feature of many cancer types. The Hh pathway has been
      documented to be indispensable for epithelial-mesenchymal transition, invasion
      and metastasis, cancer stemness, and chemoresistance. The functional
      transcription activators of the Hh pathway include the GLI proteins. Inhibition
      of the activity of GLI can interfere with almost all DNA repair types in human
      cancer, indicating that Hh/GLI functions may play an important role in enabling
      tumor cells to survive lethal types of DNA damage induced by chemotherapy and
      radiotherapy. Thus, Hh signaling presents an important therapeutic target to
      overcome DNA repair-enabled multi-drug resistance and consequently increase
      chemotherapeutic response in the treatment of cancer. 

PMID- 26197341
TI  - Roles of Chemokines and Chemokine Receptors in Obesity-Associated Insulin
      Resistance and Nonalcoholic Fatty Liver Disease.
AB  - Abundant evidence has demonstrated that obesity is a state of low-grade chronic
      inflammation that triggers the release of lipids, aberrant adipokines, pro
      inflammatory cytokines, and several chemokines from adipose tissue. This low
      grade inflammation underlies the development of insulin resistance and associated
      metabolic comorbidities such as type 2 diabetes mellitus (T2DM) and nonalcoholic
      fatty liver disease (NAFLD). During this development, adipose tissue macrophages
      accumulate through chemokine (C-C motif) receptor 2 and the ligand for this
      receptor, monocyte chemoattractant protein-1 (MCP-1), is considered to be pivotal
      for the development of insulin resistance. To date, the chemokine system is known
      to be comprised of approximately 40 chemokines and 20 chemokine receptors that
      belong to the seven-transmembrane G protein-coupled receptor family and, as a
      result, chemokines appear to exhibit a high degree of functional redundancy. Over
      the past two decades, the physiological and pathological properties of many of
      these chemokines and their receptors have been elucidated. The present review
      highlights chemokines and chemokine receptors as key contributing factors that
      link obesity to insulin resistance, T2DM, and NAFLD. 

PMID- 26197342
TI  - Functional Integration of mRNA Translational Control Programs.
AB  - Regulated mRNA translation plays a key role in control of cell cycle progression
      in a variety of physiological and pathological processes, including in the self
      renewal and survival of stem cells and cancer stem cells. While targeting mRNA
      translation presents an attractive strategy for control of aberrant cell cycle
      progression, mRNA translation is an underdeveloped therapeutic target. Regulated
      mRNAs are typically controlled through interaction with multiple RNA binding
      proteins (RBPs) but the mechanisms by which the functions of distinct RBPs bound
      to a common target mRNA are coordinated are poorly understood. The challenge now
      is to gain insight into these mechanisms of coordination and to identify the
      molecular mediators that integrate multiple, often conflicting, inputs. A first
      step includes the identification of altered mRNA ribonucleoprotein complex
      components that assemble on mRNAs bound by multiple, distinct RBPs compared to
      those recruited by individual RBPs. This review builds upon our knowledge of
      combinatorial control of mRNA translation during the maturation of oocytes from
      Xenopus laevis, to address molecular strategies that may mediate RBP diplomacy
      and conflict resolution for coordinated control of mRNA translational output.
      Continued study of regulated ribonucleoprotein complex dynamics promises valuable
      new insights into mRNA translational control and may suggest novel therapeutic
      strategies for the treatment of disease. 

PMID- 26197344
TI  - Healthcare Worker Preferences for Active Tuberculosis Case Finding Programs in
      South Africa: A Best-Worst Scaling Choice Experiment.
AB  - OBJECTIVE: Healthcare workers (HCWs) in South Africa are at a high risk of
      developing active tuberculosis (TB) due to their occupational exposures. This
      study aimed to systematically quantify and compare the preferred attributes of an
      active TB case finding program for HCWs in South Africa. METHODS: A Best-Worst
      Scaling choice experiment estimated HCW's preferences using a random-effects
      conditional logit model. Latent class analysis (LCA) was used to explore
      heterogeneity in preferences. RESULTS: "No cost", "the assurance of
      confidentiality", "no wait" and testing at the occupational health unit at one's
      hospital were the most preferred attributes. LCA identified a four class model
      with consistent differences in preference strength. Sex, occupation, and the time
      since a previous TB test were statistically significant predictors of class
      membership. CONCLUSIONS: The findings support the strengthening of occupational
      health units in South Africa to offer free and confidential active TB case
      finding programs for HCWs with minimal wait times. There is considerable
      variation in active TB case finding preferences amongst HCWs of different gender,
      occupation, and testing history. Attention to heterogeneity in preferences should
      optimize screening utilization of target HCW populations.

PMID- 26197343
TI  - Transcription Blockage Leads to New Beginnings.
AB  - Environmental agents are constantly challenging cells by damaging DNA, leading to
      the blockage of transcription elongation. How do cells deal with transcription
      blockage and how is transcription restarted after the blocking lesions are
      removed? Here we review the processes responsible for the removal of
      transcription-blocking lesions, as well as mechanisms of transcription restart.
      We also discuss recent data suggesting that blocked RNA polymerases may not
      resume transcription from the site of the lesion following its removal but,
      rather, are forced to start over from the beginning of genes. 

PMID- 26197345
TI  - The pain switch: an "ouch" detector.

PMID- 26197347
TI  - A clay permeable reactive barrier to remove Cs-137 from groundwater: Column
      experiments.
AB  - Clay minerals are reputed sorbents for Cs-137 and can be used as a low
      permeability material to prevent groundwater flow. Therefore, clay barriers are
      employed to seal Cs-137 polluted areas and nuclear waste repositories. This work
      is motivated by cases where groundwater flow cannot be impeded. A permeable and
      reactive barrier to retain Cs-137 was tested. The trapping mechanism is based on
      the sorption of cesium on illite-containing clay. The permeability of the
      reactive material is provided by mixing clay on a matrix of wood shavings. Column
      tests combined with reactive transport modeling were performed to check both
      reactivity and permeability. Hydraulic conductivity of the mixture (10(-4) m/s)
      was sufficient to ensure an adequate hydraulic performance of an eventual barrier
      excavated in most aquifers. A number of column experiments confirmed Cs retention
      under different flow rates and inflow solutions. A 1D reactive transport model
      based on a cation-exchange mechanism was built. It was calibrated with batch
      experiments for high concentrations of NH4+ and K+ (the main competitors of Cs in
      the exchange positions). The model predicted satisfactorily the results of the
      column experiments. Once validated, it was used to investigate the performance
      and duration of a 2 m thick barrier under different scenarios (flow, clay
      content, Cs-137 and K concentration).

PMID- 26197348
TI  - SPALAX new generation: New process design for a more efficient xenon production
      system for the CTBT noble gas network.
AB  - The SPALAX (Systeme de Prelevement Automatique en Ligne avec l'Analyse du Xenon)
      is one of the systems used in the International Monitoring System of the
      Comprehensive Nuclear Test Ban Treaty (CTBT) to detect radioactive xenon releases
      following a nuclear explosion. Approximately 10 years after the industrialization
      of the first system, the CEA has developed the SPALAX New Generation, SPALAX-NG,
      with the aim of increasing the global sensitivity and reducing the overall size
      of the system. A major breakthrough has been obtained by improving the sampling
      stage and the purification/concentration stage. The sampling stage evolution
      consists of increasing the sampling capacity and improving the gas treatment
      efficiency across new permeation membranes, leading to an increase in the xenon
      production capacity by a factor of 2-3. The purification/concentration stage
      evolution consists of using a new adsorbent Ag@ZSM-5 (or Ag-PZ2-25) with a much
      larger xenon retention capacity than activated charcoal, enabling a significant
      reduction in the overall size of this stage. The energy consumption of the system
      is similar to that of the current SPALAX system. The SPALAX-NG process is able to
      produce samples of almost 7 cm(3) of xenon every 12 h, making it the most
      productive xenon process among the IMS systems.

PMID- 26197349
TI  - Relationship between methamphetamine use history and segmental hair analysis
      findings of MA users.
AB  - The aim of this study was to investigate the relationship between methamphetamine
      (MA) use history and segmental hair analysis (1 and 3cm sections) and whole hair
      analysis results in Korean MA users in rehabilitation programs. Hair samples were
      collected from 26 Korean MA users. Eleven of the 26 subjects used cannabis with
      MA and two used cocaine, opiates, and MDMA with MA. Self-reported single dose of
      MA from the 26 subjects ranged from 0.03 to 0.5g/one time. Concentrations of MA
      and its metabolite amphetamine (AP) in hair were determined by gas chromatography
      mass spectrometry (GC/MS) after derivatization. The method used was well
      validated. Qualitative analysis from all 1cm sections (n=154) revealed a good
      correlation between positive or negative results for MA in hair and self-reported
      MA use (69.48%, n=107). In detail, MA results were positive in 66 hair specimens
      of MA users who reported administering MA, and MA results were negative in 41
      hair specimens of MA users who denied MA administration in the corresponding
      month. Test results were false-negative in 10.39% (n=16) of hair specimens and
      false-positive in 20.13% (n=31) of hair specimens. In false positive cases, it is
      considered that after MA cessation it continued to be accumulated in hair still,
      while in false negative cases, self-reported histories showed a small amount of
      MA use or MA use 5-7 months previously. In terms of quantitative analysis, the
      concentrations of MA in 1 and 3cm long hair segments and in whole hair samples
      ranged from 1.03 to 184.98 (mean 22.01), 2.26 to 89.33 (mean 18.71), and 0.91 to
      124.49 (mean 15.24)ng/mg, respectively. Ten subjects showed a good correlation
      between MA use and MA concentration in hair. Correlation coefficient (r) of 7
      among 10 subjects ranged from 0.71 to 0.98 (mean 0.85). Four subjects showed a
      low correlation between MA use and MA concentration in hair. Correlation
      coefficient (r) of 4 subjects ranged from 0.36 to 0.55. Eleven subjects showed a
      poor correlation between MA use and MA concentration in hair. Correlation between
      MA use and MA concentration in hair of remaining one subject could not be
      determined or calculated. In this study, the correlation between accurate MA use
      histories obtained by psychiatrists and well-trained counselors and MA
      concentrations in hair was shown. This report provides objective scientific
      findings that should considerably aid the interpretation of forensic results and
      of the results of trials related to MA use. 

PMID- 26197346
TI  - Large-Scale Phenomics Identifies Primary and Fine-Tuning Roles for CRKs in
      Responses Related to Oxidative Stress.
AB  - Cysteine-rich receptor-like kinases (CRKs) are transmembrane proteins
      characterized by the presence of two domains of unknown function 26 (DUF26) in
      their ectodomain. The CRKs form one of the largest groups of receptor-like
      protein kinases in plants, but their biological functions have so far remained
      largely uncharacterized. We conducted a large-scale phenotyping approach of a
      nearly complete crk T-DNA insertion line collection showing that CRKs control
      important aspects of plant development and stress adaptation in response to
      biotic and abiotic stimuli in a non-redundant fashion. In particular, the
      analysis of reactive oxygen species (ROS)-related stress responses, such as
      regulation of the stomatal aperture, suggests that CRKs participate in ROS/redox
      signalling and sensing. CRKs play general and fine-tuning roles in the regulation
      of stomatal closure induced by microbial and abiotic cues. Despite their great
      number and high similarity, large-scale phenotyping identified specific functions
      in diverse processes for many CRKs and indicated that CRK2 and CRK5 play
      predominant roles in growth regulation and stress adaptation, respectively. As a
      whole, the CRKs contribute to specificity in ROS signalling. Individual CRKs
      control distinct responses in an antagonistic fashion suggesting future potential
      for using CRKs in genetic approaches to improve plant performance and stress
      tolerance. 

PMID- 26197351
TI  - Quantifying the limits of fingerprint variability.
AB  - The comparison and identification of fingerprints are made difficult by
      fingerprint variability arising from distortion. This study seeks to quantify
      both the limits of fingerprint variability when subject to heavy distortion, and
      the variability observed in repeated inked planar impressions. A total of 30
      fingers were studied: 10 right slant loops, 10 plain whorls, and 10 plain arches.
      Fingers were video recorded performing several distortion movements under heavy
      deposition pressure: left, right, up, and down translation of the finger,
      clockwise and counter-clockwise torque of the finger, and planar impressions.
      Fingerprint templates, containing 'true' minutiae locations, were created for
      each finger using 10 repeated inked planar impressions. A minimal amount of
      variability, 0.18mm globally, was observed for minutiae in repeated inked planar
      impressions. When subject to heavy distortion minutiae can be displaced by
      upwards of 3mm and their orientation altered by as much as 30 degrees  in
      relation to their template positions. Minutiae displacements of 1mm and 10
      degrees  changes in orientation are readily observed. The results of this study
      will allow fingerprint examiners to identify and understand the degree of
      variability that can be reasonably expected throughout the various regions of
      fingerprints. 

PMID- 26197350
TI  - Duration of detection of methamphetamine in hair after abstinence.
AB  - Researchers in the field of hair analysis have known for at least two decades
      that test results for many chemical compounds remain positive for a considerable
      period of time after subjects have reported cessation of use. These findings were
      generally based on small sample populations or individual case studies. Within
      the last decade, hair analyses of larger populations have investigated the
      phenomenon of residual positives in abstinent individuals in order to determine
      the period of time required for various compounds to present negative hair test
      results at internationally accepted cutoff levels. Such data has primarily been
      used to establish guidelines for retesting former abusers of illicit drugs in
      order to evaluate claims of abstinence. To date, research has focused on cocaine
      and opiates. The present study is the first to examine the duration of detection
      of methamphetamine (MA) and its metabolite amphetamine (AP) in the hair of
      chronic MA users who recently ceased their consumption of the drug. The study
      population (n=63) consisted of inpatients at a hospital drug rehabilitation
      program in Chiang Mai, Thailand. Drug taking behavior was collected by personal
      interview at the time of enrollment. Subjects provided hair samples at
      approximately monthly intervals for MA and AP analysis by gas chromatography-mass
      spectrometry at 0.2ng/mg cutoff levels. The correlation of baseline MA and AP
      concentrations in hair at the beginning of abstinence with corresponding duration
      of detection indicated great individual variability for the rate of clearance of
      MA and AP from hair. In regard to duration of detection, the majority of chronic
      MA users remained MA positive for up to about 90 days of reported abstinence, but
      by 120 days, the detection rate had fallen to about 16%. All subjects tested
      negative for MA after 153 days of abstinence. For AP, the limit of the duration
      of detection was reached at 106 days. With the adoption of a margin of safety to
      compensate for outlier individual variability, the present study affirmed that
      hair analysis of chronic MA abusers should test negative for MA after 6 months of
      claimed abstinence. 

PMID- 26197352
TI  - Sinus Wall Resurfacing for Patients With Temporal Bone Venous Sinus Diverticulum
      and Ipsilateral Pulsatile Tinnitus.
AB  - BACKGROUND: Pulsatile tinnitus (PT) caused by venous sinus diverticulum is a
      relatively common, potentially incapacitating condition. Although treatment via
      an external approach or endovascular coiling has been reported, much remains
      unknown about the possible pathophysiological mechanisms and appropriate
      management of PT. OBJECTIVE: To review our case series of PT resulting from
      either sigmoid sinus diverticulum (SSD) or middle cranial fossa venous sinus
      diverticulum (MFD-VS) and to discuss the possible pathophysiological mechanisms
      and desirable treatment options. METHODS: Four PT patients with either SSD or MFD
      VS were treated with transmastoid resurfacing. In 1 case, a revision operation
      was performed as a result of recurrence of PT 4.5 years after the initial
      operation. The medical records and temporal bone imaging findings were
      retrospectively reviewed. RESULTS: PT was resolved in all cases immediately after
      transmastoid resurfacing, but 1 patient in whom bone wax was used for initial
      resurfacing experienced PT 4.5 years later. The PT was successfully managed with
      revision resurfacing with autologous bone chips/bone cement. In the other cases,
      the resolution of PT lasted throughout a median follow-up of 5.75 years. Notably,
      2 of 4 cases had preoperative low-frequency hearing loss (LFHL) and experienced
      immediate postoperative improvement in LFHL. CONCLUSION: PT resulting from either
      SSD or MFD-VS can be treated successfully with transmastoid resurfacing of the
      venous wall. Preoperative ipsilesional LFHL and the improvement of hearing
      threshold after surgical intervention may be preoperative and postoperative
      surrogate objective signatures of PT. To ensure the resolution of symptoms,
      secure reconstruction with firm materials and long-term follow-up are mandatory.

PMID- 26197353
TI  - Rational Design and Synthesis of Thioridazine Analogues as Enhancers of the
      Antituberculosis Therapy.
AB  - Tuberculosis, caused by Mycobacterium tuberculosis, is still one of the leading
      infectious diseases globally. Therefore, novel approaches are needed to face this
      disease. Efflux pumps are known to contribute to the emergence of M. tuberculosis
      drug resistance. Thioridazine has shown good anti-TB properties both in vitro and
      in vivo, likely due to its capacity to inhibit efflux mechanisms. Here we report
      the design and synthesis of a number of putative efflux inhibitors inspired by
      the structure of thioridazine. Compounds were evaluated for their in vitro and ex
      vivo activity against M. tuberculosis H37Rv. Compared to the parent molecule,
      some of the compounds synthesized showed higher efflux inhibitory capacity, less
      cytotoxicity, and a remarkable synergistic effect with anti-TB drugs both in
      vitro and in human macrophages, demonstrating their potential to be used as
      coadjuvants for the treatment of tuberculosis. 

PMID- 26197354
TI  - Update on melanoma epigenetics.
AB  - PURPOSE OF REVIEW: Over the last years, our understanding in molecular biology of
      melanoma has grown significantly and many genetic alterations have been
      identified affecting melanoma pathogenesis. This growing evidence has led to the
      development of targeted therapies which are showing promising clinical results.
      In addition to genetic alterations, an increasing number of studies have recently
      demonstrated the role of epigenetics in melanoma development and progression.
      Here, we summarize the current data on epigenetic research in melanoma. RECENT
      FINDINGS: MicroRNA (miRNA) expression profiling studies have identified several
      miRNAs implicated in melanoma cell cycle and proliferation, cell migration and
      invasion, as well as miRNAs involved in apoptosis and immune response. Abnormal
      methylation profiling has been associated with melanoma progression and to date
      aberrant hypermethylation in more than 70 genes has been described. Recent works
      have highlighted the increasing evidence of the role of histone modification as a
      central regulatory event in melanoma pathogenesis. SUMMARY: Many of these
      epigenetic biomarkers may have potential diagnostic, prognostic and therapeutic
      implications. Future approach might be using a combination of genetic and
      epigenetic biomarkers.

PMID- 26197355
TI  - The evolution of magnanimity : When is it better to give than to receive?
AB  - Conspicuous consumption associated with status reinforcement behavior can be
      explained in terms of costly signaling, or strategic handicap theory, first
      articulated by Zahavi and later formalized by Grafen. A theory is introduced
      which suggests that the evolutionary raison d'etre of status reinforcement
      behavior lies not only in its effects on lifetime reproductive success, but in
      its positive effects on the probability of survival through infrequent,
      unpredictable demographic bottlenecks. Under some circumstances, such "wasteful"
      displays may take the form of displays of altruistic behavior and generosity on
      the part of high status individuals, in that is signals the ability to bear the
      short-term costs of being generous or "cooperative," while at the same time
      reinforcing the long-term benefits of higher status. 

PMID- 26197357
TI  - Fluctuating asymmetry and aggression in boys.
AB  - Fluctuating asymmetry (FA) is small deviations from perfect symmetry in normally
      bilaterally symmetrical traits. We examined the relationship between FA of five
      body traits (ear height, length of three digits, and ankle circumference) and
      self-reported scores of physical and verbal aggression in a sample of 90 boys
      aged 10 to 15 years. The relationships between FA and scores of aggression
      (particularly physical aggression) were found to be negative; in other words, the
      most symmetrical boys showed highest aggression. One trait (ankle circumference)
      showed the characteristics of "ideal" FA-parametric mean of zero and a normal
      distribution. Mean asymmetries calculated from six repeated measures of ankle FA
      in 30 subjects taken over a period of five months showed strong negative
      associations with scores of physical aggression which were independent of age,
      height, and weight.It is argued that soft tissue "cyclical" FA (as opposed to
      "fixed" bony FA) is dependent on the secretion of hormones: for example,
      cortisol. Causal associations between behavioral traits such as aggresion and
      hormones will lead to similar correlations between FA and behavior. 

PMID- 26197356
TI  - Lust, attraction, and attachment in mammalian reproduction.
AB  - This paper proposes that mammals exhibit three primary emotion categories for
      mating and reproduction: (1) the sex drive, or lust, characterized by the craving
      for sexual gratification; (2) attraction, characterized by increased energy and
      focused attention on one or more potential mates, accompanied in humans by
      feelings of exhilaration, "intrusive thinking" about a mate, and the craving for
      emotional union with this mate or potential mate; and (3) attachment,
      characterized by the maintenance of close social contact in mammals, accompanied
      in humans by feelings of calm, comfort, and emotional union with a mate. Each
      emotion category is associated with a discrete constellation of neural
      correlates, and each evolved to direct a specific aspect of reproduction. The sex
      drive is associated primarily with the estrogens and androgens; it evolved to
      motivate individuals to seek sexual union. The attraction system is associated
      primarily with the catecholamines; it evolved to facilitate mate choice, enabling
      individuals to focus their mating effort on preferred partners. The attachment
      system is associated primarily with the peptides, vasopressin, and oxytocin; it
      evolved to motivate individuals to engage in positive social behaviors and assume
      species-specific parental duties.During the evolution of the genus Homo, these
      emotion systems became increasingly independent of one another, a phenomenon that
      contributes to human mating flexibility and the wide range of contemporary human
      mating and reproductive strategies. 

PMID- 26197358
TI  - Parent and offspring strategies in the transition at adolescence.
AB  - Adolescence signifies a transition from the use of prereproductive to
      reproductive strategies in the life history of Homo sapiens. Insofar as human
      generations overlap, events at adolescence, surrounding the onset of puberty,
      offer a unique glimpse into human adaptation from the point of view of the
      changing strategies of both parents and offspring. The timing of puberty is an
      important life history trait that varies between species, but also between and
      within the sexes in human beings. The onset of puberty marks the beginning of the
      reproductive life, is affected by previous experience, and serves as a trigger
      for behavioral change. Surbey (1988, 1990) reported relationships between father
      absence, heightened levels of childhood stress, and early menarche and considered
      them within the context of human evolutionary history. Subsequently, similar
      findings have been reported in a number of human populations and have been
      interpreted from several evolutionary perspectives. This article discusses the
      extent to which these and related findings regarding alterations in the timing of
      human puberty reflect evolved parental or offspring strategies. It entails a
      consideration of the applicability of the concepts of phenotypic plasticity,
      nonadaptive genetic variation, and conditional and alternative reproductive
      strategies in describing the interwoven nature of strategies employed by parent
      and child in the transition at adolescence. 

PMID- 26197360
TI  - Disentangling fast and slow attentional influences of negative and taboo spoken
      words in the emotional Stroop paradigm.
AB  - Although the influence of the emotional content of stimuli on attention has been
      considered as occurring within trial, recent studies revealed that the
      presentation of such stimuli would also involve a slow component. The aim of the
      present study was to investigate fast and slow effects of negative (Exp. 1) and
      taboo (Exp. 2) spoken words. For this purpose, we used an auditory variant of the
      emotional Stroop paradigm in which each emotional word was followed by a sequence
      of neutral words. Replicating results from our previous study, we observed slow
      but no fast effects of negative and taboo words, which we interpreted as
      reflecting difficulties to disengage attention from their emotional dimension.
      Interestingly, while the presentation of a negative word only delayed the
      processing of the immediately subsequent neutral word, slow effects of taboo
      words were long-lasting. Nevertheless, such attentional effects were only
      observed when the emotional words were presented in the first block of trials,
      suggesting that once participants develop strategies to perform the task,
      attention-grabbing effects of emotional words disappear. Hence, far from being
      automatic, the occurrence of these effects would depend on participants'
      attentional set. 

PMID- 26197362
TI  - Quantifying Land Use Impacts on Biodiversity: Combining Species-Area Models and
      Vulnerability Indicators.
AB  - Habitat degradation and subsequent biodiversity damage often take place far from
      the place of consumption because of globalization and the increasing level of
      international trade. Informing consumers and policy makers about the biodiversity
      impacts "hidden" in the life cycle of imported products is an important step
      toward achieving sustainable consumption patterns. Spatially explicit methods are
      needed in life cycle assessment to accurately quantify biodiversity impacts of
      products and processes. We use the Countryside species-area relationship (SAR) to
      quantify regional species loss due to land occupation and transformation for five
      taxa and six land use types in 804 terrestrial ecoregions. Further, we calculate
      vulnerability scores for each ecoregion based on the fraction of each species'
      geographic range (endemic richness) hosted by the ecoregion and the IUCN assigned
      threat level of each species. Vulnerability scores are multiplied with SAR
      predicted regional species loss to estimate potential global extinctions per unit
      of land use. As a case study, we assess the land use biodiversity impacts of 1 kg
      of bioethanol produced using six different feed stocks in different parts of the
      world. Results show that the regions with highest biodiversity impacts differed
      markedly when the vulnerability of species was included.

PMID- 26197363
TI  - Academic Involvement: A Treatment for Regulatory Fatigue.

PMID- 26197364
TI  - Drug Shortages in Perioperative Medicine: Past, Present, or Future?

PMID- 26197365
TI  - Ethics of Disclosure Regarding Drug Shortages That Affect Patient Care.

PMID- 26197366
TI  - Data Agnosticism and Implications on Method Comparison Studies.

PMID- 26197367
TI  - Can the Viscoelastic Parameter alpha-Angle Distinguish Fibrinogen from Platelet
      Deficiency and Guide Fibrinogen Supplementation?
AB  - Viscoelastic tests such as thrombelastography (TEG, Haemoscope Inc., Niles, IL)
      and thromboelastometry (ROTEM, Tem International GmbH, Munich, Germany),
      performed in whole blood, are increasingly used at the point-of-care to
      characterize coagulopathic states and guide hemostatic therapy. An algorithm,
      based on a mono-analysis (kaolin-activated assay) approach, was proposed in the
      TEG patent (issued in 2004) where the alpha-angle and the maximum amplitude
      parameters are used to guide fibrinogen supplementation and platelet
      administration, respectively. Although multiple assays for both the TEG and ROTEM
      devices are now available, algorithms based on TEG mono-analysis are still used
      in many institutions. In light of more recent findings, we discuss here the
      limitations and inaccuracies of the mono-analysis approach. Research shows that
      both alpha-angle and maximum amplitude parameters reflect the combined
      contribution of fibrinogen and platelets to clot strength. Therefore, although
      TEG mono-analysis is useful for identifying a coagulopathic state, it cannot be
      used to discriminate between fibrin/fibrinogen and/or platelet deficits,
      respectively. Conversely, the use of viscoelastic methods where 2 assays can be
      run simultaneously, one with platelet inhibitors and one without, can effectively
      allow for the identification of specific coagulopathic states, such as
      insufficient fibrin formation or an insufficient contribution of platelets to
      clot strength. Such information is critical for making the appropriate choice of
      hemostatic therapy.

PMID- 26197368
TI  - Lung Injury After One-Lung Ventilation: A Review of the Pathophysiologic
      Mechanisms Affecting the Ventilated and the Collapsed Lung.
AB  - Lung injury is the leading cause of death after thoracic surgery. Initially
      recognized after pneumonectomy, it has since been described after any period of 1
      lung ventilation (OLV), even in the absence of lung resection. Overhydration and
      high tidal volumes were thought to be responsible at various points; however, it
      is now recognized that the pathophysiology is more complex and multifactorial.
      All causative mechanisms known to trigger ventilator-induced lung injury have
      been described in the OLV setting. The ventilated lung is exposed to high strain
      secondary to large, nonphysiologic tidal volumes and loss of the normal
      functional residual capacity. In addition, the ventilated lung experiences
      oxidative stress, as well as capillary shear stress because of hyperperfusion.
      Surgical manipulation and/or resection of the collapsed lung may induce lung
      injury. Re-expansion of the collapsed lung at the conclusion of OLV invariably
      induces duration-dependent, ischemia-reperfusion injury. Inflammatory cytokines
      are released in response to localized injury and may promote local and
      contralateral lung injury. Protective ventilation and volatile anesthesia lessen
      the degree of injury; however, increases in biochemical and histologic markers of
      lung injury appear unavoidable. The endothelial glycocalyx may represent a common
      pathway for lung injury creation during OLV, because it is damaged by most of the
      recognized lung injurious mechanisms. Experimental therapies to stabilize the
      endothelial glycocalyx may afford the ability to reduce lung injury in the
      future. In the interim, protective ventilation with tidal volumes of 4 to 5 mL/kg
      predicted body weight, positive end-expiratory pressure of 5 to 10 cm H2O, and
      routine lung recruitment should be used during OLV in an attempt to minimize
      harmful lung stress and strain. Additional strategies to reduce lung injury
      include routine volatile anesthesia and efforts to minimize OLV duration and
      hyperoxia. 

PMID- 26197369
TI  - Multimodal Evaluation of Aortic Regurgitation After Mitral and Tricuspid Valve
      Repairs.

PMID- 26197370
TI  - Transesophageal Echocardiographic Assessment of Left Ventricular Mass.

PMID- 26197371
TI  - Intraoperative Evaluation of Paravalvular Regurgitation by Transesophageal
      Echocardiography.

PMID- 26197372
TI  - Joint Commission and Regulatory Fatigue/Weakness/Overabundance/Distraction:
      Clinical Context Matters.

PMID- 26197374
TI  - Expecting the Unexpected: Perspectives on Stillbirth and Late Termination of
      Pregnancy for Fetal Anomalies.
AB  - Expectant mothers and their spouses spend months preparing to eagerly welcome
      their much-anticipated baby into their family. Stillbirth or a diagnosis of life
      limiting fetal anomalies comes as a devastating turn of events for affected women
      and their families. From the time of diagnosis to intervention (i.e., induction
      of labor for stillbirth or late termination of pregnancy for fetal anomalies),
      affected women often feel vulnerable and abandoned, with many experiencing long
      term psychological and emotional effects. Knowledge of obstetric management,
      ethical and medical challenges, and psychological aspects have evolved in recent
      years. Familiarity with this emerging knowledge better prepares the obstetric
      anesthesiologist to deliver effective and empathic care. Encounters with women
      experiencing stillbirth and life-limiting fetal anomalies prompted this review of
      current evidence regarding parturient' perspectives on their care as they set out
      on the road to recovery. 

PMID- 26197375
TI  - Cell Salvage in Obstetrics.
AB  - Intraoperative cell salvage is a strategy to decrease the need for allogeneic
      blood transfusion. Traditionally, cell salvage has been avoided in the obstetric
      population because of the perceived risk of amniotic fluid embolism or induction
      of maternal alloimmunization. With advances in cell salvage technology, the risks
      of cell salvage in the obstetric population parallel those in the general
      population. Levels of fetal squamous cells in salvaged blood are comparable to
      those in maternal venous blood at the time of placental separation. No definite
      cases of amniotic fluid embolism have been reported and appear unlikely with
      modern equipment. Cell salvage is cost-effective in patients with predictably
      high rates of transfusion, such as parturients with abnormal placentation. 

PMID- 26197373
TI  - The Surgical Care Improvement Project Antibiotic Guidelines: Should We Expect
      More Than Good Intentions?
AB  - Since 2006, the Surgical Care Improvement Project (SCIP) has promoted 3
      perioperative antibiotic recommendations designed to reduce the incidence of
      surgical site infections. Despite good evidence for the efficacy of these
      recommendations, the efforts of SCIP have not measurably improved the rates of
      surgical site infections. We offer 3 arguments as to why SCIP has fallen short of
      expectations. We then suggest a reorientation of quality improvement efforts to
      focus less on reporting, and incentivizing adherence to imperfect metrics, and
      more on creating local and regional quality collaboratives to educate clinicians
      about how to improve practice. Ultimately, successful quality improvement
      projects are behavioral interventions that will only succeed to the degree that
      they motivate individual clinicians, practicing within a particular context, to
      do the difficult work of identifying failures and iteratively working toward
      excellence. 

PMID- 26197376
TI  - Survey of the National Drug Shortage Effect on Anesthesia and Patient Safety: A
      Patient Perspective.
AB  - BACKGROUND: There are few data on patients' desire to be informed of drug
      shortages before elective surgery. We surveyed patients who had previously
      undergone laparoscopic cholecystectomy for their opinions. METHODS: Nine hundred
      forty-nine Mayo Clinic patients were invited to participate in the survey. The
      postal survey posed a hypothetical surgical scenario and requested answers
      regarding the desire to be informed and to postpone scheduled surgery because of
      neostigmine shortage. Comparison was made with Canadian patients from a hospital
      in Ontario. RESULTS: Most of the 256 respondents wanted "to be told by the
      anesthesia doctor about the neostigmine shortage" if there were "slight
      differences" in side effects between the drug combinations (P < 0.0001). The
      percentage of patients wanting to know was 76.2% (95% confidence interval, 70.5%
      81.3%). Secondary analyses tested the validity and reliability of the survey.
      With each increase in the differences in substituted drug's side effects, there
      was a progressive increase in the patients' desire for information (P < 0.0001;
      73.2%, 76.2%, and 95.7% of 246, 256, and 253 respondents, respectively) and
      preference for delaying surgery (P< 0.0001; 33.6%, 39.4%, and 80.9% of 238, 246,
      and 241 respondents, respectively). There was no association with respondents'
      sex (P = 0.19), age (P = 0.76), educational level (P = 0.39), or country (United
      States versus Canada [n = 58]; P = 0.87). CONCLUSIONS: The majority (>50%) of
      surveyed patients want to be informed of drug shortages that might affect their
      care.

PMID- 26197361
TI  - Progress in corneal wound healing.
AB  - Corneal wound healing is a complex process involving cell death, migration,
      proliferation, differentiation, and extracellular matrix remodeling. Many
      similarities are observed in the healing processes of corneal epithelial, stromal
      and endothelial cells, as well as cell-specific differences. Corneal epithelial
      healing largely depends on limbal stem cells and remodeling of the basement
      membrane. During stromal healing, keratocytes get transformed to motile and
      contractile myofibroblasts largely due to activation of transforming growth
      factor-beta (TGF-beta) system. Endothelial cells heal mostly by migration and
      spreading, with cell proliferation playing a secondary role. In the last decade,
      many aspects of wound healing process in different parts of the cornea have been
      elucidated, and some new therapeutic approaches have emerged. The concept of
      limbal stem cells received rigorous experimental corroboration, with new markers
      uncovered and new treatment options including gene and microRNA therapy tested in
      experimental systems. Transplantation of limbal stem cell-enriched cultures for
      efficient re-epithelialization in stem cell deficiency and corneal injuries has
      become reality in clinical setting. Mediators and course of events during stromal
      healing have been detailed, and new treatment regimens including gene (decorin)
      and stem cell therapy for excessive healing have been designed. This is a very
      important advance given the popularity of various refractive surgeries entailing
      stromal wound healing. Successful surgical ways of replacing the diseased
      endothelium have been clinically tested, and new approaches to accelerate
      endothelial healing and suppress endothelial-mesenchymal transformation have been
      proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to
      activate TGF-beta inhibitor SMAD7. Promising new technologies with potential for
      corneal wound healing manipulation including microRNA, induced pluripotent stem
      cells to generate corneal epithelium, and nanocarriers for corneal drug delivery
      are discussed. Attention is also paid to problems in wound healing understanding
      and treatment, such as lack of specific epithelial stem cell markers, reliable
      identification of stem cells, efficient prevention of haze and stromal scar
      formation, lack of data on wound regulating microRNAs in keratocytes and
      endothelial cells, as well as virtual lack of targeted systems for drug and gene
      delivery to select corneal cells. 

PMID- 26197377
TI  - Quality of Supervision as an Independent Contributor to an Anesthesiologist's
      Individual Clinical Value.
AB  - BACKGROUND: Although the clinical (operating room) production of individual
      anesthesiologists has been measured in multiple related ways (e.g., hours of
      direct clinical care), the same is not true for the quality of that effort. In
      our study, we consider the quality of clinical supervision provided by
      anesthesiologists who are supervising anesthesia residents and nurse
      anesthetists. The quality of the daily supervision can be measured reliably and
      validly using the scale developed by de Oliveira Filho et al. If clinical
      production and supervisory quality were not positively correlated, then it would
      be important for departments to measure the quality of clinical supervision
      because, essentially, the clinical value provided by an anesthesiologist would be
      correlated with, but not necessarily proportional to, their clinical hours.
      METHODS: Our department sends daily e-mail requests to anesthesia residents and
      nurse anesthetists to evaluate the supervision provided by each anesthesiologist
      with whom they worked the previous day in an operating room setting. We compared
      anesthesiologists' clinical activity (total operating room hours) and supervision
      scores obtained during the first (July 1, 2013 to December 31, 2013) and last
      (July 1, 2014 to December 31, 2014) of 3 consecutive 6-month periods. During the
      first 6 months, anesthesiologists received no feedback regarding the supervision
      scores. During the last 6 months, there was feedback to all anesthesiologists
      regarding their individual supervision scores and comments provided by residents
      (during the preceding 6 months) and nurse anesthetists (during the preceding 12
      months). RESULTS: Anesthesiologists' mean supervision scores were not positively
      correlated with their total (weekly) hours of clinical activity. For the first 6
      months, the correlations were r = -0.18 among scores provided by residents (P =
      0.92 for positive correlation, N = 57 anesthesiologists) and r = -0.04 among
      scores provided by nurse anesthetists (P = 0.70, N = 61). For the last 6 months,
      the correlations were r = -0.28 (P = 0.98) and r = -0.10 (P = 0.79),
      respectively. Pairwise by anesthesiologist, the mean supervision scores provided
      by residents increased by 0.08 +/- 0.01 points (P < 0.0001, N = 44). The mean
      supervision scores provided by nurse anesthetists increased by 0.28 +/- 0.02
      points (P < 0.0001, N = 49). CONCLUSIONS: When anesthesiologists supervise
      anesthesia residents and nurse anesthetists, the amount of clinical work
      performed and the quality of the supervision provided do not necessarily follow
      one another. Thus, faculty supervision scores serve as an independent measure of
      the contribution of an individual anesthesiologist to the care of the patient.
      Furthermore, when supervision quality is monitored and feedback is provided to
      anesthesiologists, quality can increase. The results suggest that anesthesiology
      department managers should not only be monitoring (and perhaps reporting) the
      quality of their departments' level of supervision, but also establishing
      processes so that individual anesthesiologists can learn about the quality of
      supervision they provide.

PMID- 26197378
TI  - Smarter Clinical Checklists: How to Minimize Checklist Fatigue and Maximize
      Clinician Performance.

PMID- 26197379
TI  - More Research Is Required to Demonstrate a Relationship Between Intrapartum Pain
      Management and Postpartum Mood Disorders.

PMID- 26197380
TI  - In Response.

PMID- 26197381
TI  - Revealing the Potential of New Regional Oximeters.

PMID- 26197382
TI  - In Response.

PMID- 26197383
TI  - Reply to Body Fat Composition Predicts Infectious Complications After Bowel
      Resection in Crohn's Disease.

PMID- 26197384
TI  - Reply to Use of CT Scan in Ulcerative Colitis Patients Presenting to the
      Emergency Department.

PMID- 26197385
TI  - Effect of substituted stilbenes on platelet function.
AB  - Stilbenes, including resveratrol, are polyphenols provided with protective
      actions on the cardiovascular system. Some natural derivatives of resveratrol,
      like pterostilbene, have a better bioavailability than the parent compound. The
      aim of the present study was to prepare different substituted stilbenes
      (dimethylallyloxy-stilbene, dimethylallyloxy-pterostilbene) and compare them with
      resveratrol, p-hydroxy-stilbene and pterostilbene for their biologic activities
      on platelet aggregation, platelet radical oxygen species (ROS) production, and
      platelet nitric oxide (NO) synthesis. The results show that the increase of
      stilbene derivative lipophilicity enhances their biologic activities. 

PMID- 26197386
TI  - A Chemical Route to Activation of Open Metal Sites in the Copper-Based Metal
      Organic Framework Materials HKUST-1 and Cu-MOF-2.
AB  - Open coordination sites (OCSs) in metal-organic frameworks (MOFs) often function
      as key factors in the potential applications of MOFs, such as gas separation, gas
      sorption, and catalysis. For these applications, the activation process to remove
      the solvent molecules coordinated at the OCSs is an essential step that must be
      performed prior to use of the MOFs. To date, the thermal method performed by
      applying heat and vacuum has been the only method for such activation. In this
      report, we demonstrate that methylene chloride (MC) itself can perform the
      activation role: this process can serve as an alternative "chemical route" for
      the activation that does not require applying heat. To the best of our knowledge,
      no previous study has demonstrated this function of MC, although MC has been
      popularly used in the pretreatment step prior to the thermal activation process.
      On the basis of a Raman study, we propose a plausible mechanism for the chemical
      activation, in which the function of MC is possibly due to its coordination with
      the Cu(2+) center and subsequent spontaneous decoordination. Using HKUST-1 film,
      we further demonstrate that this chemical activation route is highly suitable for
      activating large-area MOF films. 

PMID- 26197387
TI  - Effects of Autumn and Spring Heat Waves on Seed Germination of High Mountain
      Plants.
AB  - Alpine plants are considered to be particularly vulnerable to climate change and
      related extreme episodes, such as heat waves. Despite growing interest in the
      impact of heat waves on alpine plants, knowledge about their effects on
      regeneration is still fragmentary. Recruitment from seeds will be crucial for the
      successful migration and survival of these species and will play a key role in
      their future adaptation to climate change. In this study, we assessed the impacts
      of heat waves on the seed germination of 53 high mountain plants from the
      Northern Apennines (Italy). The seeds were exposed to laboratory simulations of
      three seasonal temperature treatments, derived from real data recorded at a
      meteorological station near the species growing site, which included two heat
      wave episodes that occurred both in spring 2003 and in autumn 2011. Moreover, to
      consider the effect of increasing drought conditions related to heat waves, seed
      germination was also investigated under four different water potentials. In the
      absence of heat waves, seed germination mainly occurred in spring, after seeds
      had experienced autumn and winter seasons. However, heat waves resulted in a
      significant increase of spring germination in c. 30% of the species and elicited
      autumn germination in 50%. When heat waves were coupled with drought, seed
      germination decreased in all species, but did not stop completely. Our results
      suggest that in the future, heat waves will affect the germination phenology of
      alpine plants, especially conditionally dormant and strictly cold-adapted
      chorotypes, by shifting the emergence time from spring to autumn and by
      increasing the proportion of emerged seedlings. The detrimental effects of heat
      waves on recruitment success is less likely to be due to the inhibition of seed
      germination per se, but rather due to seedling survival in seasons, and
      temperature and water conditions that they are not used to experiencing. Changes
      in the proportion and timing of emergence suggest that there may be major
      implications for future plant population size and structure.

PMID- 26197388
TI  - NanR, a Transcriptional Regulator That Binds to the Promoters of Genes Involved
      in Sialic Acid Metabolism in the Anaerobic Pathogen Clostridium perfringens.
AB  - Among many other virulence factors, Clostridium perfringens produces three
      sialidases NanH, NanI and NanJ. NanH lacks a secretion signal peptide and is
      predicted to be an intracellular enzyme, while NanI and NanJ are secreted.
      Previously, we had identified part of an operon encoding NanE (epimerase) and
      NanA (sialic acid lyase) enzymes. Further analysis of the entire operon suggests
      that it encodes a complete pathway for the transport and metabolism of sialic
      acid along with a putative transcriptional regulator, NanR. The addition of 30 mM
      N-acetyl neuraminic acid (Neu5Ac) to a semi-defined medium significantly enhanced
      the growth yield of strain 13, suggesting that Neu5Ac can be used as a nutrient.
      C. perfringens strain 13 lacks a nanH gene, but has NanI- and NanJ-encoding
      genes. Analysis of nanI, nanJ, and nanInanJ mutants constructed by homologous
      recombination revealed that the expression of the major sialidase, NanI, was
      induced by the addition of Neu5Ac to the medium, and that in separate
      experiments, the same was true of a nanI-gusA transcriptional fusion. For the
      nanI and nanJ genes, primer extension identified three and two putative
      transcription start sites, respectively. Gel mobility shift assays using purified
      NanR and DNA from the promoter regions of the nanI and nanE genes showed high
      affinity, specific binding by NanR. We propose that NanR is a global regulator of
      sialic acid-associated genes and that it responds, in a positive feedback loop,
      to the concentration of sialic acid in the cell.

PMID- 26197389
TI  - Deletion of cyp125 Confers Increased Sensitivity to Azoles in Mycobacterium
      tuberculosis.
AB  - Mycobacterium tuberculosis is able to utilize cholesterol as a carbon source, and
      this ability is linked to its virulence in macrophages and in the mouse model of
      infection. The M. tuberculosis cytochrome P450 Cyp125 plays a key role in
      cholesterol metabolism being involved in the first steps of its degradation.
      Cyp125 is a cholesterol hydroxylase which is essential for cholesterol catabolism
      in M. bovis BCG and some strains of M. tuberculosis. We generated an unmarked, in
      frame deletion of Cyp125 in M. tuberculosis H37Rv. The deletion strain was able
      to grow as well as wild-type in medium containing glucose as the carbon source.
      The Cyp125 deletion strain was more sensitive to growth inhibition by
      clotrimazole consistent with the ability of Cyp125 to bind azoles with high
      affinity. The deletion strain showed no difference in sensitivity to nitric oxide
      or hydrogen peroxide and was not attenuated for growth inside THP-1 human
      macrophage-like cells. These data suggest that the attenuation of virulence seen
      in operon deletion strains is not linked to the lack of Cyp125 alone.

PMID- 26197391
TI  - K-bZIP Mediated SUMO-2/3 Specific Modification on the KSHV Genome Negatively
      Regulates Lytic Gene Expression and Viral Reactivation.
AB  - SUMOylation is associated with epigenetic regulation of chromatin structure and
      transcription. Epigenetic modifications of herpesviral genomes accompany the
      transcriptional switch of latent and lytic genes during the virus life cycle.
      Here, we report a genome-wide comparison of SUMO paralog modification on the KSHV
      genome. Using chromatin immunoprecipitation in conjunction with high-throughput
      sequencing, our study revealed highly distinct landscape changes of SUMO paralog
      genomic modifications associated with KSHV reactivation. A rapid and widespread
      deposition of SUMO-2/3, compared with SUMO-1, modification across the KSHV genome
      upon reactivation was observed. Interestingly, SUMO-2/3 enrichment was inversely
      correlated with H3K9me3 mark after reactivation, indicating that SUMO-2/3 may be
      responsible for regulating the expression of viral genes located in low
      heterochromatin regions during viral reactivation. RNA-sequencing analysis showed
      that the SUMO-2/3 enrichment pattern positively correlated with KSHV gene
      expression profiles. Activation of KSHV lytic genes located in regions with high
      SUMO-2/3 enrichment was enhanced by SUMO-2/3 knockdown. These findings suggest
      that SUMO-2/3 viral chromatin modification contributes to the diminution of viral
      gene expression during reactivation. Our previous study identified a SUMO-2/3
      specific viral E3 ligase, K-bZIP, suggesting a potential role of this enzyme in
      regulating SUMO-2/3 enrichment and viral gene repression. Consistent with this
      prediction, higher K-bZIP binding on SUMO-2/3 enrichment region during
      reactivation was observed. Moreover, a K-bZIP SUMO E3 ligase dead mutant, K-bZIP
      L75A, in the viral context, showed no SUMO-2/3 enrichment on viral chromatin and
      higher expression of viral genes located in SUMO-2/3 enriched regions during
      reactivation. Importantly, virus production significantly increased in both SUMO
      2/3 knockdown and KSHV K-bZIP-L75A mutant cells. These results indicate that SUMO
      2/3 modification of viral chromatin may function to counteract KSHV reactivation.
      As induction of herpesvirus reactivation may activate cellular antiviral regimes,
      our results suggest that development of viral SUMO E3 ligase specific inhibitors
      may be an avenue for anti-virus therapy. 

PMID- 26197390
TI  - GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial
      Lymphocytes following Bone Marrow Transplantation.
AB  - Specific G protein coupled receptors (GPRs) regulate the proper positioning,
      function, and development of immune lineage subsets. Here, we demonstrate that
      GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs) of the
      small intestine following bone marrow transplantation. Through analysis of
      transcriptional microarray data, we find that GPR18 is highly expressed in IELs,
      lymphoid progenitors, and mature follicular B cells. To establish the
      physiological role of this largely uncharacterized GPR, we generated Gpr18-/-
      mice. Despite high levels of GPR18 expression in specific hematopoietic
      progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis.
      Moreover, antibody responses following immunization with hapten-protein
      conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady
      state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone
      marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically
      required for the optimal restoration of small intestine TCRgammadelta+ and
      TCRalphabeta+ CD8alphaalpha+ IELs. In contrast, GPR18 is dispensable for the
      reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow
      reconstitutes small intestine IELs similarly to controls in athymic recipients.
      Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as
      Citrobacter rodentium infections or graft versus host disease. These data reveal
      highly specific requirements for GPR18 in the development and reconstitution of
      thymus-derived intestinal IEL subsets in the steady-state and after bone marrow
      transplantation.

PMID- 26197392
TI  - Solid-state properties and dissolution behaviour of tablets containing co
      amorphous indomethacin-arginine.
AB  - Co-amorphous drug formulations provide the possibility to stabilize a drug in its
      amorphous form by interactions with low molecular weight compounds, e.g. amino
      acids. Recent studies have shown the feasibility of spray drying as a technique
      to manufacture co-amorphous indomethacin-arginine in a larger production scale.
      In this work, a tablet formulation was developed for a co-amorphous salt, namely
      spray dried indomethacin-arginine (SD IND-ARG). The effects of compaction
      pressure on tablet properties, physical stability and dissolution profiles under
      non-sink conditions were examined. Dissolution profiles of tablets with SD IND
      ARG (TAB SD IND-ARG) were compared to those of tablets containing a physical
      mixture of crystalline IND and ARG (TAB PM IND-ARG) and to the dissolution of
      pure spray dried powder. Concerning tableting, the developed formulation allowed
      for the preparation of tablets with a broad range of compaction pressures
      resulting in different porosities and tensile strengths. XRPD results showed
      that, overall, no crystallization occurred neither during tableting nor during
      long-term storage. Dissolution profiles of TAB SD IND-ARG showed an immediate
      release of IND by erosion. The solubility of crystalline IND was exceeded by a
      factor of about 4, which was accompanied by a slow crystallization. For TAB PM
      IND-ARG, an in situ amorphization of IND in the presence of ARG was observed. As
      a result, a supersaturation was obtained, too, followed by a faster
      crystallization compared to TAB SD IND-ARG. In conclusion, the AUC24h of TAB SD
      IND-ARG was twofold higher than the AUC24h of TAB PM IND-ARG. Interestingly,
      different plateaus were obtained for TAB SD IND-ARG, TAB PM IND-ARG and pure SD
      IND-ARG after 24h dissolution, which could be explained by the formation of
      different polymorphic forms of indomethacin. 

PMID- 26197393
TI  - Suppression of Propionibacterium acnes Infection and the Associated Inflammatory
      Response by the Antimicrobial Peptide P5 in Mice.
AB  - The cutaneous inflammation associated with acne vulgaris is caused by the
      anaerobic bacterium Propionibacterium acnes through activation of the innate
      immune system in the skin. Current standard treatments for acne have limitations
      that include adverse effects and poor efficacy in many patients, making
      development of a more effective therapy highly desirable. In the present study,
      we demonstrate the protective effects of a novel customized alpha-helical
      cationic peptide, P5, against P. acnes-induced inflammatory responses in vitro
      and in vivo. Application of P5 significantly reduced expression of two
      inflammatory cytokines IL-8 and TNF-alpha in P. acnes-treated primary human
      keratinocytes, where P5 appeared to act in part by binding to bacterial
      lipoteichoic acid, thereby suppressing TLR2-to-NF-kappaB signaling. In addition,
      in a mouse model of acne vulgaris, P5 exerted both anti-inflammatory and
      antimicrobial effects against P. acnes, but exerted no cytotoxic effects against
      skin cells. These results demonstrate that P5, and perhaps other cationic
      antimicrobial peptides, offer the unique ability to reduce numbers P. acnes cells
      in the skin and to inhibit the inflammation they trigger. This suggests these
      peptides could potentially be used to effectively treat acne without adversely
      affecting the skin. 

PMID- 26197396
TI  - Using Pooled Local Expert Opinions (PLEO) to Discern Patterns in Sightings of
      Live and Dead Manatees (Trichechus senegalensis, Link 1785) in Lower Sanaga
      Basin, Cameroon.
AB  - We aimed at unveiling patterns in live and dead manatee sightings in the Lower
      Sanaga Basin, Cameroon. For this purpose, the expert opinions of 133 local
      fishers were collected during in-person interviews, distilled using categorical
      data analysis, and checked against scientific literature. The five main results
      are as follows: manatees were sighted averagely once a week in lakes, rivers, and
      the coast & estuaries, mostly in group sizes of 2-3; the odds of sighting live
      manatees (respectively dead manatees) decreased (respectively increased) from
      inland lakes to estuaries and the coast, via rivers; manatee carcasses were
      reported in all habitats, albeit more frequently in rivers; a distribution map
      based on fishers' reports show two manatee concentration areas: Lake Ossa and the
      Malimba-Mbiako section of River Sanaga; the number of manatees was perceived as
      increasing despite incidental and directed catches. Thus, our findings
      corroborate earlier assessments of the Lower Sanaga Basin as being a major
      manatee conservation area. Additionally, from these results and the literature,
      we identified three hypotheses about local manatee persistence: deep pools such
      as lakes offer year round sanctuaries, not just dry-season refugia; seasonality
      of specific habitat variables determine manatee occurrence patterns; and local
      variability in habitat encroachment mediate the meta-population dynamics of
      manatee in the Lower Sanaga Basin. Finally, we examine the implications for data
      requirements in light of the small ecological scale at which the surveyed fishers
      ply their trade. Thus, consonant with the Malawi principles for the ecosystem
      approach to management (www.cbd.int/ecosystem), we recommend collecting data
      preferably at landscape scale, through a participatory monitoring program that
      fully integrates scientific and traditional knowledge systems. This program
      should include, amongst others, a standardised necropsy protocol for collecting
      mortality and biological data together with sonar and radio-telemetry technology
      to discern manatee use and movements between critical habitat components. 

PMID- 26197394
TI  - On the Effect of Sodium Chloride and Sodium Sulfate on Cold Denaturation.
AB  - Both sodium chloride and sodium sulfate are able to stabilize yeast frataxin,
      causing an overall increase of its thermodynamic stability curve, with a decrease
      in the cold denaturation temperature and an increase in the hot denaturation one.
      The influence of low concentrations of these two salts on yeast frataxin
      stability can be assessed by the application of a theoretical model based on
      scaled particle theory. First developed to figure out the mechanism underlying
      cold denaturation in water, this model is able to predict the stabilization of
      globular proteins provided by these two salts. The densities of the salt
      solutions and their temperature dependence play a fundamental role.

PMID- 26197395
TI  - Diffused Intra-Oocyte Hydrogen Peroxide Activates Myeloperoxidase and
      Deteriorates Oocyte Quality.
AB  - Hydrogen peroxide (H2O2) is a relatively long-lived signaling molecule that plays
      an essential role in oocyte maturation, implantation, as well as early embryonic
      development. Exposure to relatively high levels of H2O2 functions efficiently to
      accelerate oocyte aging and deteriorate oocyte quality. However, little precise
      information exists regarding intra-oocyte H2O2 concentrations, and its diffusion
      to the oocyte milieu. In this work, we utilized an L-shaped amperometric
      integrated H2O2-selective probe to directly and quantitatively measure the real
      time intra-oocyte H2O2 concentration. This investigation provides an exact
      measurement of H2O2 in situ by reducing the possible loss of H2O2 caused by
      diffusion or reactivity with other biological systems. This experiment suggests
      that the intra-oocyte H2O2 levels of oocytes obtained from young animals are
      reasonably high and remained constant during the procedure measurements. However,
      the intra-oocyte H2O2 concentration dropped significantly (40-50% reduction) in
      response to catalase pre-incubation, suggesting that the measurements are truly
      H2O2 based. To further confirm the extracellular diffusion of H2O2, oocytes were
      incubated with myeloperoxidase (MPO), and the diffused H2O2 triggered MPO
      chlorinating activity. Our results show that the generated hypochlorous acid
      (HOCl) facilitated the deterioration in oocyte quality, a process that could be
      prevented by pre-incubating the oocytes with melatonin, which was experimentally
      proven to be oxidized utilizing HPLC methods. This study is the first to
      demonstrate direct quantitative measurement of intracellular H2O2, and its
      extracellular diffusion and activation of MPO as well as its impact on oocyte
      quality. These results may help in designing more accurate treatment plans in
      assisted reproduction under inflammatory conditions. 

PMID- 26197397
TI  - Adaptive Advantage of Myrmecochory in the Ant-Dispersed Herb Lamium amplexicaule
      (Lamiaceae): Predation Avoidance through the Deterrence of Post-Dispersal Seed
      Predators.
AB  - Seed dispersal by ants (myrmecochory) is found worldwide, but the benefits that
      plants obtain from this mutualism remain uncertain. In the present study, we
      conducted laboratory experiments to demonstrate seed predator avoidance as a
      benefit of myrmecochory using the annual ant-dispersed herb Lamium amplexicaule,
      the disperser ant Tetramorium tsushimae, and the seed predatory burrower bug
      Adomerus rotundus. We compared the predation intensity of Lamium amplexicaule
      seeds by Adomerus rotundus under the presence or absence of Tetramorium
      tsushimae. Both the number of seeds sucked by Adomerus rotundus adults and the
      feeding duration of sucked seeds by nymphs were significantly reduced in the
      presence of ants. This effect was most likely due to the behavioral alteration of
      Adomerus rotundus in response to the ant presence, because ants seldom predated
      Adomerus rotundus during the experiment. Our results demonstrated that the
      presence of ants decreases post-dispersal seed predation, even when the ants do
      not bury the seeds. The present study thus suggests that the non-consumptive
      effects of ants on seed predators benefit myrmecochorous plants.

PMID- 26197399
TI  - Invasive assessment of the coronary microcirculation in the catheter laboratory.
AB  - Historically much of our understanding of the coronary circulation has been
      centered towards the epicardial vessels. However, recent work has highlighted the
      importance of the coronary microcirculation across a broad spectrum of clinical
      conditions in influencing patient outcomes. Therefore an ability to measure
      microvascular function is most valuable. While evaluation of the epicardial
      coronary circulation is widely understood, interrogation of the coronary
      microcirculation is more complex. Many methods are available to assess the
      integrity of the microcirculation in the catheter laboratory. This review will
      discuss the physiology of the coronary microcirculation and evaluate the utility
      of available invasive techniques.

PMID- 26197400
TI  - The natural history of guidelines: the case of aortopathy related to bicuspid
      aortic valves.
AB  - Clinical guidelines represent statements that seek to synthesize the best
      evidence to guide a course of action to improve health outcomes and more cost
      effective use of resources. However, even when the evidence is not definitive,
      comprehensive documents are still needed to guide clinical decision-making. In
      these circumstances, guidelines are inevitably affected by perceptions of the
      problem and their possible solutions. From 1998 to 2014, 10 different
      international guidelines have focused on the aortopathy related to bicuspid
      aortic valves. Recommended thresholds for intervention started at a cutoff level
      of 5.5cm in 1998, reached a nadir of 4 to 4.5cm in 2010, and returned to a 5.5cm
      cutoff level in 2014. During this time, no conclusive objective proof was
      published to support either an aggressive or conservative strategy. The
      consequence was that an undefined number of patients underwent surgery (and
      potential complications thereof) at an earlier disease stage than might have been
      necessary. This experience might provide a clue as to how guidelines evolve, and
      provide insight as to how to avoid a similar process in the future.

PMID- 26197398
TI  - Differentiation between Solitary Cerebral Metastasis and Astrocytoma on the Basis
      of Subventricular Zone Involvement on Magnetic Resonance Imaging.
AB  - PURPOSE: To determine the relationship between the subventricular zone (SVZ) and
      astrocytoma based on magnetic resonance imaging (MRI) and whether SVZ involvement
      can be used to distinguish solitary cerebral metastases (SCMs) from astrocytomas.
      METHODS: This retrospective study involved 154 patients with solitary low-grade
      astrocytoma (LGA), high-grade astrocytoma (HGA), and SCM, who underwent T1
      weighted imaging (T1WI), Gd-DTPA-enhanced T1WI, and T2-weighted imaging (T2WI) or
      fluid-attenuated inversion recovery (FLAIR) T2WI. The spatial relationship
      between the tumor and SVZ was classified as "involvement" or "segregation" on
      contrast-enhanced T1WI for enhanced tumors and T2WI/FLAIR T2WI for non-enhanced
      tumors. Patient-based SVZ-contact rates were compared between the LGA, HGA, and
      SCM groups. The frequencies of involvement of various lateral ventricle regions
      by astrocytoma were compared. The correlation between SVZ involvement and tumor
      necrosis was analyzed. RESULTS: Patient-based SVZ-contact rates in SCM, LGA, and
      HGA were 24.1%, 68.8%, and 85.4%, respectively. Univariate analysis showed that
      the SVZ-contact rate was significantly different between SCM and astrocytoma
      (24.1% vs. 75.2% P < 0.001), also between LGA and HGA (68.1% vs. 85.4% P=0.037).
      After the tumor volume was adjusted as a covariate, SVZ-contact rates still
      differed between SCMs and astrocytomas (Odds ratio [OR]: 4.58, 95% Confidence
      interval [CI]: 1.65 to 12.8, P=0.004). Tumor volume differed between LGA and HGA
      (P< 0.001), and influenced the association between SVZ involvement and
      astrocytoma grade (P = 0.05). Among the lateral ventricle regions, the frontal
      horn was the most frequently involved by astrocytomas. SVZ-contact rates were
      higher in necrosis group compared with non-necrosis groups (83.9% vs. 50.0%, P <
      0.001) among astrocytoma patients. Necrosis positively correlated with SVZ
      involvement in astrocytomas (rs = 0.342, P < 0.001), but did not correlate with
      SVZ involvement in SCMs (P = 0.193). CONCLUSIONS: Compared to SCMs, solitary
      cerebral astrocytomas exhibited spatial proximity to the SVZ, which might
      distinguish the supratentorial astrocytomas from SCMs.

PMID- 26197401
TI  - Myocarditis in takotsubo syndrome: may be a trigger and/or a feature.

PMID- 26197402
TI  - Transapical transcatheter aortic valve implantation using a new second-generation
      TAVI system - J-ValveTM for high-risk patients with aortic valve diseases:
      Initial results with 90-day follow-up.
AB  - BACKGROUND: To evaluate the safety and efficacy of transcatheter aortic valve
      implantation (TAVI) for patients with aortic stenosis (AS) or pure/dominant
      aortic regurgitation (AR) using the J-ValveTM system. METHODS: Twenty patients
      with isolated aortic valve disease (11 with pure/dominant AR and 9 with AS) at
      high risk for open-heart surgery were enrolled in this study. The mean Logistic
      Euro-SCORE I was 27.2+/-8.2% (mean age 74.5+/-4.7years). Four sizes of prosthesis
      were used for annular size up to 21 mm (n=1), 23mm (n=2), 25mm (n=10) and 27mm
      (n=7). Clinical and echocardiographic evaluations were performed at baseline,
      post-procedure and follow-up. The primary endpoint was all-cause mortality.
      Secondary endpoints were procedural success, major adverse events as well as
      echocardiographic performance. RESULTS: TAVI with the J-ValveTM device was
      successfully performed in 19 patients (95%). Conversion to surgical valve
      replacement was necessary in one patient due to prosthesis embolization. No
      mortality occurred during 90 days follow-up. Pacemaker implantation for new onset
      conduction disorders was necessary in one patient (5%). For patient with severe
      AS, post-procedure TAVI resulted in favorable reduction of mean transvalvular
      gradients (55.3+/-8.5 vs. 16.4+/-13.3 mmHg, P<0.01). Mean transvalvular gradient
      was also favorable in AR patients after valve implantation (6.9+/-1mmHg). The
      majority of patients had none or trivial paravalvular regurgitation (17/19) while
      none had moderate or severe paravalvular regurgitation. CONCLUSION: Trans-apical
      TAVI using the J-ValveTM prosthesis is potentially an effective treatment option
      for patients with AS or pure/dominant AR at high risk for open-heart surgery.

PMID- 26197403
TI  - DPP-4 inhibition ameliorates atherosclerosis by priming monocytes into M2
      macrophages.
AB  - OBJECTIVE: Glipitins are widely used for the treatment of type 2 diabetic
      patients. In addition to their improvement of glycemic control, animal studies
      have suggested an independent anti-atherosclerotic effect of gliptins.
      Nevertheless, recent clinical trials regarding long-term effects of gliptin
      therapy on vascular events have been disappointing. This discrepancy led us to
      better dissect the functional role of SDF-1/CXCR4 signaling as a potential
      mechanism underlying gliptin action. The study should give improved understanding
      of the potential of gliptin therapy in the prevention and treatment of
      atherosclerosis. METHODS AND RESULTS: In an ApoE-/- mouse model on high
      cholesterol diet, long-term treatment with the DPP-4 inhibitor Sitagliptin
      significantly reduced atherosclerosic plaque load in the aorta. Flow cytometry
      analyses showed an enrichment of M2 macrophages in the aortic wall under gliptin
      therapy. Importantly, the number of recruited CD206+ macrophages was inversely
      correlated with total plaque area while no correlation was found for the overall
      macrophage population or M1 macrophages. Blockade of CXCR4/SDF-1 signaling by
      AMD3100 inhibited aortic M2 accumulation and the therapeutic effect of
      Sitagliptin. Correspondingly, Sitagliptin shifted the polarization profile of
      macrophages towards a M2-like phenotype. CONCLUSION: Sitagliptin-mediated
      inhibition of early atherosclerosis is based on M2-polarization during monocyte
      differentiation via the SDF-1/CXCR4 signaling. In contrast to earlier assumptions
      gliptin treatment might be especially effective in prevention of atherosclerosis.

PMID- 26197405
TI  - Transcatheter pulmonary valve implantation: a cross-sectional US experience.

PMID- 26197404
TI  - Rationale and design of GISSI OUTLIERS VAR Study in bicuspid aortic valve
      patients: prospective longitudinal, multicenter study to investigate correlation
      between surgical, echo distinctive features, histologic and genetic findings in
      phenotypically homogeneous outlier cases.
AB  - BACKGROUND/OBJECTIVES: Bicuspid aortic valve (BAV) is the most common congenital
      heart disorder, affecting up to 2% of the population. Involvement of aortic root
      and ascending aorta (aneurysm or, eventually, dissection) is frequent in patients
      with pathologic or normal functioning BAV. Unfortunately, there are no well-known
      correlations between valvular and vascular diseases. In VAR protocol, with a new
      strategy of research, we analysemultiple aspects of BAV disease through
      correlation between surgical, echo, histologic and genetic findings in
      phenotypically homogeneous outlier cases. METHODS: VAR protocol is a prospective,
      longitudinal, multicenter study. It observes 4 homogeneous small groups of BAV
      surgical patients (15 patients each): isolated aortic regurgitation, isolated
      ascending aortic aneurysm, aortic regurgitation associated with aortic aneurysm,
      isolated aortic stenosis in older patients (>60years). Echo analysis is extended
      to first-degree relatives and, in case of BAV, genetic test is performed.
      Patients and relatives are enrolled in 10 cardiac surgery/cardiologic centers
      throughout Italy. CONCLUSIONS: The aim of the study is to identify predictors of
      favorable or unfavorable evolution of BAV in terms of valvular dysfunction and/or
      aortic aneurysm. Correlations between different features could help in
      identification of various BAV risk groups, rationalizing follow-up and treatment.

PMID- 26197406
TI  - Can apical ballooning cardiomyopathy and anterior STEMI be differentiated based
      on beta1 and beta2-adrenergic receptors polymorphisms?
AB  - AIM: Catecholamine excess along with an exaggerated sympathetic stimulation
      appears to play a major role in the pathophysiological mechanism of tako-tsubo
      cardiomyopathy (TTC), which mimics acute ST-elevation myocardial infarction
      (STEMI). The aim of the present study was to investigate differences in the
      distribution of allelic variants of beta1- and beta2-adrenoceptors between TTC
      and anterior STEMI patients compared to normal subjects. METHODS AND RESULTS:
      beta1- and/or beta2-adrenoceptor polymorphisms in 97 patients with TTC (92
      females, 96%; mean age 66.8+/-11.6years; range 35 to 87years) were compared with
      81 patients with anterior STEMI (77 females, 95%; mean age 72.5+/-12.8years;
      range 32 to 96years) and 101 controls (95 females, 94%; mean age 62.3+/
      10.4years; range 44 to 92years). Differences in genotype frequencies were
      assessed using the Pearson chi(2) test. beta1-Adrenoceptor (Gly389Arg) and beta2
      adrenoceptor (Arg16Gly and Gln27Glu) genotype frequencies were significantly
      different among groups (p<0.001, p=0.024, p=0.008, respectively). However,
      differences did not achieve statistical significance when TTC and anterior STEMI
      patients were compared by post-hoc analysis. The cardiovascular risk factor
      profile was worse in anterior STEMI patients, who more often had a history of
      systemic arterial hypertension, diabetes and coronary artery disease.
      CONCLUSIONS: In a large TTC cohort compared with anterior STEMI patients, beta
      adrenoceptor polymorphisms were similar. However, the cardiovascular risk factor
      profile was different between the two groups. beta-Adrenoceptor polymorphisms in
      TTC patients differed from normal subjects.

PMID- 26197407
TI  - Long sheath filling defect during left atrial appendage occlusion device
      placement.

PMID- 26197408
TI  - Brock procedure: 52 years of effective palliation for Tetralogy of Fallot.

PMID- 26197409
TI  - Neighbourhood Characteristics and Long-Term Air Pollution Levels Modify the
      Association between the Short-Term Nitrogen Dioxide Concentrations and All-Cause
      Mortality in Paris.
AB  - BACKGROUND: While a great number of papers have been published on the short-term
      effects of air pollution on mortality, few have tried to assess whether this
      association varies according to the neighbourhood socioeconomic level and long
      term ambient air concentrations measured at the place of residence. We explored
      the effect modification of 1) socioeconomic status, 2) long-term NO2 ambient air
      concentrations, and 3) both combined, on the association between short-term
      exposure to NO2 and all-cause mortality in Paris (France). METHODS: A time
      stratified case-crossover analysis was performed to evaluate the effect of short
      term NO2 variations on mortality, based on 79,107 deaths having occurred among
      subjects aged over 35 years, from 2004 to 2009, in the city of Paris. Simple and
      double interactions were statistically tested in order to analyse effect
      modification by neighbourhood characteristics on the association between
      mortality and short-term NO2 exposure. The data was estimated at the census block
      scale (n=866). RESULTS: The mean of the NO2 concentrations during the five days
      prior to deaths were associated with an increased risk of all-cause mortality:
      overall Excess Risk (ER) was 0.94% (95%CI=[0.08;1.80]. A higher risk was revealed
      for subjects living in the most deprived census blocks in comparison with higher
      socioeconomic level areas (ER=3.14% (95%CI=[1.41-4.90], p<0.001). Among these
      deprived census blocks, excess risk was even higher where long-term average NO2
      concentrations were above 55.8 MUg/m3 (the top tercile of distribution): ER=4.84%
      (95%CI=[1.56;8.24], p for interaction=0.02). CONCLUSION: Our results show that
      people living in census blocks characterized by low socioeconomic status are more
      vulnerable to air pollution episodes. There is also an indication that people
      living in these disadvantaged census blocks might experience even higher risk
      following short-term air pollution episodes, when they are also chronically
      exposed to higher NO2 levels.

PMID- 26197410
TI  - Near-infrared fluorescence heptamethine carbocyanine dyes mediate imaging and
      targeted drug delivery for human brain tumor.
AB  - Brain tumors and brain metastases are among the deadliest malignancies of all
      human cancers, largely due to the cellular blood-brain and blood-tumor barriers
      that limit the delivery of imaging and therapeutic agents from the systemic
      circulation to tumors. Thus, improved strategies for brain tumor visualization
      and targeted treatment are critically needed. Here we identified and synthesized
      a group of near-infrared fluorescence (NIRF) heptamethine carbocyanine dyes and
      derivative NIRF dye-drug conjugates for effective imaging and therapeutic
      targeting of brain tumors of either primary or metastatic origin in mice, which
      is mechanistically mediated by tumor hypoxia and organic anion-transporting
      polypeptide genes. We also demonstrate that these dyes, when conjugated to
      chemotherapeutic agents such as gemcitabine, significantly restricted the growth
      of both intracranial glioma xenografts and prostate tumor brain metastases and
      prolonged survival in mice. These results show promise in the application of NIRF
      dyes as novel theranostic agents for the detection and treatment of brain tumors.

PMID- 26197411
TI  - Rapidly light-activated surgical protein glue inspired by mussel adhesion and
      insect structural crosslinking.
AB  - Currently approved surgical tissue glues do not satisfy the requirements for
      ideal bioadhesives due to limited adhesion in wet conditions and severe
      cytotoxicity. Herein, we report a new light-activated, mussel protein-based
      bioadhesive (LAMBA) inspired by mussel adhesion and insect dityrosine
      crosslinking chemistry. LAMBA exhibited substantially stronger bulk wet tissue
      adhesion than commercially available fibrin glue and good biocompatibility in
      both in vitro and in vivo studies. Besides, the easily tunable, light-activated
      crosslinking enabled an effective on-demand wound closure and facilitated wound
      healing. Based on these outstanding properties, LAMBA holds great potential as an
      ideal surgical tissue glue for diverse medical applications, including sutureless
      wound closures of skin and internal organs. 

PMID- 26197413
TI  - Effect of intravitreal Rho kinase inhibitor ripasudil (K-115) on feline retinal
      microcirculation.
AB  - Ripasudil (K-115) is a novel Rho kinase inhibitor with a potent intraocular
      pressure-lowering effect. However, it is unclear whether ripasudil affects the
      retinal blood flow (RBF). We investigated the effect of ripasudil on feline
      retinal microcirculation. Ripasudil (5 MUM, 50 MUM or 5 mM; n = 5 each
      concentration) or vehicle (PBS; n = 5) was injected intravitreally. The vessel
      diameter (D) and blood velocity (V) were measured by laser Doppler velocimetry
      simultaneously in the first-order retinal arterioles and the RBF was calculated.
      The measurements started 5 min before the injection and were performed every 10
      min for 120 min. After the intravitreal injection, the retinal circulatory
      parameters did not change significantly in PBS or 5 MUM of ripasudil. The blood V
      and RBF increased significantly compared to baseline, whereas the vessel D did
      not change significantly in 50 MUM and 5 mM of ripasudil. The V in 50 MUM, and
      the V and RBF in 5 mM of ripasudil significantly increased compared to those in
      PBS. Intravitreal administration of ripasudil increased the blood V and RBF in
      cats, suggesting that ripasudil has the potential to improve the retinal blood
      flow. 

PMID- 26197412
TI  - Engineering an "infectious" T(reg) biomimetic through chemoselective tethering of
      TGF-beta1 to PEG brush surfaces.
AB  - Modulation of immunological responses to allografts following transplantation is
      of pivotal importance to improving graft outcome and duration. Of the many
      approaches, harnessing the dominant tolerance induced by regulatory T cells
      (Treg) holds tremendous promise. Recent studies have highlighted the unique
      potency of cell surface-bound TGF-beta1 on Treg for promoting infectious
      tolerance, i.e. to confer suppressive capacity from one cell to another. To mimic
      this characteristic, TGF-beta1 was chemoselectively tethered to inert and viable
      polymer grafting platforms using Staudinger ligation. We report the synthesis and
      functional characterization of these engineered TGF-beta1 surfaces. Inert beads
      tethered with TGF-beta1 were capable of efficiently converting naive CD4(+)
      CD62L(hi) T cells to functional Treg. Concordantly, translation of conjugation
      scheme from inert surfaces to viable cells also led to efficient generation of
      functional Treg. Further, the capacity of these platforms to generate antigen
      specific Treg was demonstrated. These findings illustrate the unique faculty of
      tethered TGF-beta1 biomaterial platforms to function as an "infectious" Treg and
      provide a compelling approach for generating tolerogenic microenvironments for
      allograft transplantation. 

PMID- 26197414
TI  - Survival cannibalism or sociopolitical intimidation? : Explaining perimortem
      mutilation in the American Southwest.
AB  - Over the past two decades, archaeologists and physical anthropologists
      investigating the prehistoric Anasazi culture have identified numerous cases of
      suspected cannibalism. Many scholars have suggested that starvation caused by
      environmental degradation induced people to eat one another, but the growing
      number of cases as well as their temporal and spatial distribution challenge this
      conclusion. At the same time, some scholars have questioned the validity of the
      osteoarchaeological indicators that are used to identify cannibalism in
      collections of mutilated human remains. To address these concerns, this study
      attempts to reconstruct the behaviors that produced the Anasazi skeletal trauma
      by first examining ethnographic, ethnohistoric, and archaeological material for
      analogues useful for interpreting mutilated human remains and then correlating
      these analogues with the evidence from the Southwest. The patterns suggest that
      different behaviors are responsible for the Anasazi skeletal mutilation seen in
      different time periods. To explain these differences, the study employs game
      theoretical models that examine how changing social and physical contexts altered
      the sociopolitical strategies that Anasazi groups would likely have employed. The
      results suggest that violent mutilation and perhaps cannibalism was an
      intentional sociopolitical strategy of intimidation used during Pueblo II (A.D.
      900-1100), while environmental changes after this period promoted resource-based
      warfare and the incidental skeletal trauma associated with this behavior. 

PMID- 26197415
TI  - Attachment and time preference : Relations between early stress and sexual
      behavior in a sample of American university women.
AB  - This paper investigates hypotheses drawn from two sources: (1) Belsky, Steinberg,
      and Draper's (1991) attachment theory model of the development of reproductive
      strategies, and (2) recent life history models and comparative data suggesting
      that environmental risk and uncertainty may be potent determinants of the optimal
      tradeoff between current and future reproduction. A retrospective, self-report
      study of 136 American university women aged 19-25 showed that current
      recollections of early stress (environmental risk and uncertainty) were related
      to individual differences in adult time preference and adult sexual behavior, and
      that individual differences in time preference were related to adult attachment
      organization and sexual behavior. These results are consistent with the
      hypothesis that perceptions of early stress index environmental risk and
      uncertainty and mediate the attachment process and the development of
      reproductive strategies. On this view individual differences in time preference
      are considered to be part of the attachment theoretical construct of an internal
      working model, which itself is conceived as an evolved algorithm for the
      contingent development of alternative reproductive strategies. 

PMID- 26197416
TI  - Reproductive strategies and sex-biased investment : Suggested roles of breast
      feeding and wet-nursing.
AB  - Sex-biased investment in children has been explored in a historic population in
      northern England, 1600 to 1800, following a family reconstitution study. An
      examination of the wills and other available data identified three social groups:
      the elite, tradesmen, and subsistence farmers. The community lived under marginal
      conditions with poor and fluctuating levels of nutrition; infant and child
      mortalities were high. Clear differences were found between the social groups,
      and it is suggested that the elite wetnursed their daughters whereas the elite
      mother breast-fed her sons for only a short period and introduced supplementary
      feeding early. The wives of the tradesmen probably breast-fed both sexes for the
      same length of time. Subsistence farmers may have weaned their sons earlier than
      daughters. The results are discussed in terms of possible differences in
      investment strategies. The investment strategy of the elite group was probably
      male-biased but may, in practice, have favored the female offspring. 

PMID- 26197417
TI  - Draft genome sequence of Talaromyces islandicus ("Penicillium islandicum") WF-38
      12, a neglected mold with significant biotechnological potential.
AB  - Talaromyces (Penicillium) islandicus is a common mold found in stored rice or
      cereals. It has a highly versatile metabolism characterized by the secretion of
      numerous biopolymer degrading enzymes, mycotoxins, and anthraquinones that
      altogether offer a broad range of potential industrial applications. Here, we
      report the draft genome sequence of Talaromyces islandicus, which provides the
      basis of a biotechnological usage of this species. 

PMID- 26197418
TI  - Delta(9)-Tetrahydrocannabinolic acid synthase production in Pichia pastoris
      enables chemical synthesis of cannabinoids.
AB  - Delta(9)-Tetrahydrocannabinol (THC) is of increasing interest as a pharmaceutical
      and bioactive compound. Chemical synthesis of THC uses a laborious procedure and
      does not satisfy the market demand. The implementation of biocatalysts for
      specific synthesis steps might be beneficial for making natural product
      availability independent from the plant. Delta(9)-Tetrahydrocannabinolic acid
      synthase (THCAS) from C. sativa L. catalyzes the cyclization of cannabigerolic
      acid (CBGA) to Delta(9)-tetrahydrocannabinolic acid (THCA), which is non
      enzymatically decarboxylated to THC. We report the preparation of THCAS in
      amounts sufficient for the biocatalytic production of THC(A). Active THCAS was
      most efficiently obtained from Pichia pastoris. THCAS was produced on a 2L
      bioreactor scale and the enzyme was isolated by single-step chromatography with a
      specific activity of 73Ug(-1)total protein. An organic/aqueous two-liquid phase
      setup for continuous substrate delivery facilitated in situ product removal. In
      addition, THCAS activity in aqueous environments lasted for only 20min whereas
      the presence of hexane stabilized the activity over 3h. In conclusion, production
      of THCAS in P. pastoris Mut(S) KM71 KE1, subsequent isolation, and its
      application in a two-liquid phase setup enables the synthesis of THCA on a mg
      scale. 

PMID- 26197419
TI  - Development and application of a high-throughput platform for perfusion-based
      cell culture processes.
AB  - A high-throughput (HT) cell culture model has been established for the support of
      perfusion-based cell culture processes operating at high cell densities. To mimic
      perfusion, the developed platform takes advantage of shake tubes and operates
      them in a batch-refeed mode with daily medium exchange to supply the cultures
      with nutrients and remove toxic byproducts. By adjusting the shaking parameters,
      such as the speed and setting angle, we have adapted the shake tubes to a semi
      continuous production of a recombinant enzyme in a perfusion-like mode. We have
      demonstrated that the developed model can be used to select clones and cell
      culture media ahead of process optimization studies in bioreactors and confirmed
      the applicability of shake tubes to a perfusion-like cell culture reaching ~50E6
      viable cells/mL. Furthermore, through regular cell mass removal and periodic
      medium exchange we have successfully maintained satellite cultures of bench-top
      perfusion bioreactors, achieving a sustainable cell culture performance at >=30E6
      viable cells/mL and viabilities >80% for over 58 days. The established HT model
      is a unique and powerful tool that can be used for the development and screening
      of media formulations, or for testing selected process parameters during both
      process optimization and manufacturing support campaigns. 

PMID- 26197420
TI  - An improved fluorescence polarization assay in 5'-nuclease reaction for gene
      promoter methylation detection.
AB  - The detection of gene promoter methylation plays increasing roles in personalized
      medicine. In this study, an improved gene promoter methylation assay based on
      fluorescence polarization in 5'-nuclease reaction was developed. The novel assay
      offered a homogeneous annealing and cleavage reaction fully integrated with PCR
      which used a probe labeled with fluorescence without quencher to obtain the
      decreased fluorescence polarization values. In this platform, gene promoter
      methylated and unmethylated alleles were detected simultaneously in a tube. O(6)
      methylguanine-DNA methyltransferase gene promoter methylation in 103 glioma
      tissue samples and epidermal growth factor receptor gene promoter methylation in
      116 primary non-small-cell lung carcinoma tissue samples were detected by the
      novel assay and sequencing, absolute quantitative analysis of methylated allele
      in parallel. The accuracy of the results measured by the improved fluorescence
      polarization assay was evaluated using the paired-samples t test. No significant
      difference was found ( P>0.05). Therefore, the improved fluorescence polarization
      assay in 5'-nuclease reaction demonstrated a homogeneous, reliable and cost
      effective method for gene promoter methylation analysis in clinic. That would
      provide a scientific basis for applying a reasonable therapeutic regimen in
      future treatment. 

PMID- 26197421
TI  - Systemic lupus erythematosus: An update for ophthalmologists.
AB  - Systemic lupus erythematosus (SLE) is a life-threatening multisystem inflammatory
      condition that may affect almost any part of the eye. We provide an update for
      the practicing ophthalmologist comprising a systematic review of the recent
      literature presented in the context of current knowledge of the pathogenesis,
      diagnosis, and treatment of this condition. We review recent advances in the
      understanding of the influence of genetic and environmental factors on the
      development of SLE. Recent changes in the diagnostic criteria for SLE are
      considered. We assess the potential for novel molecular biomarkers to find a
      clinical application in disease diagnosis and stratification and in the
      development of therapeutic agents. We discuss limited forms of SLE and their
      differentiation from other collagen vascular disorders and review recent evidence
      underlying the use of established and novel therapeutics in this condition,
      including specific implications regarding monitoring for ocular toxicity
      associated with antimalarials. 

PMID- 26197422
TI  - Facilitating the afforestation of Mediterranean polluted soils by nurse shrubs.
AB  - The revegetation of polluted sites and abandoned agricultural soils is critical
      to reduce soil losses and to control the spread of soil pollution in the
      Mediterranean region, which is currently exposed to the greatest soil erosion
      risk in Europe. However, events of massive plant mortality usually occur during
      the first years after planting, mainly due to the adverse conditions of high
      irradiance and drought stress. Here, we evaluated the usefulness of considering
      the positive plant-plant interactions (facilitation effect) in the afforestation
      of polluted agricultural sites, using pre-existing shrubs as nurse plants. We
      used nurse shrubs as planting microsites for acorns of Quercus ilex (Holm oak)
      along a gradient of soil pollution in southwestern Spain, and monitored seedling
      growth, survival, and chemical composition during three consecutive years.
      Seedling survival greatly increased (from 20% to more than 50%) when acorns were
      sown under shrub, in comparison to the open, unprotected matrix. Facilitation of
      seedling growth by shrubs increased along the gradient of soil pollution, in
      agreement with the stress gradient hypothesis that predicts higher intensity of
      the facilitation effects with increasing abiotic stress. Although the
      accumulation of trace elements in seedling leaves was higher underneath shrub,
      the shading conditions provided by the shrub canopy allowed seedlings to cope
      with the toxicity provoked by the concurrence of low pH and high trace element
      concentrations in the most polluted sites. Our results show that the use of
      shrubs as nurse plants is a promising tool for the cost-effective afforestation
      of polluted lands under Mediterranean conditions. 

PMID- 26197423
TI  - Slaughterhouse wastewater characteristics, treatment, and management in the meat
      processing industry: A review on trends and advances.
AB  - A thorough review of advancement in slaughterhouse wastewater (SWW)
      characteristics, treatment, and management in the meat processing industry is
      presented. This study also provides a general review of the environmental
      impacts, health effects, and regulatory frameworks relevant to the SWW
      management. A significant progress in high-rate anaerobic treatment, nutrient
      removal, advanced oxidation processes (AOPs), and the combination of biological
      treatment and AOPs for SWW treatment is highlighted. The treatment processes are
      described and few examples of their applications are given. Conversely, few
      advances are accounted in terms of waste minimization and water use reduction,
      reuse, and recycle in slaughterhouses, which may offer new alternatives for cost
      effective waste management. An overview of the most frequently applied
      technologies and combined processes for organic and nutrient removal during the
      last decade is also summarized. Several types of individual and combined
      processes have been used for the SWW treatment. Nevertheless, the selection of a
      particular technology depends on the characteristics of the wastewater, the
      available technology, and the compliance with regulations. This review
      facilitates a better understanding of current difficulties that can be found
      during production and management of the SWW, including treatment and
      characteristics of the final effluent. 

PMID- 26197424
TI  - Mercury-impacted scrap metal: Source and nature of the mercury.
AB  - The reuse and recycling of industrial solid wastes such as scrap metal is
      supported and encouraged both internationally and domestically, especially when
      such wastes can be used as substitutes for raw material. However, scrap metal
      processing facilities, such as mini-mills, have been identified as a source of
      mercury (Hg) emissions in the United States. This research aims to better define
      some of the key issues related to the source and nature of mercury in the scrap
      metal waste stream. Overall, it is difficult to pinpoint the key mercury sources
      feeding into scrap metal recycling facilities, quantify their associated mercury
      concentrations, or determine which chemical forms are most significant. Potential
      sources of mercury in scrap metal include mercury switches from discarded
      vehicles, electronic-based scrap from household appliances and related industrial
      systems, and Hg-impacted scrap metal from the oil and gas industry. The form of
      mercury associated with scrap metal varies and depends on the source type. The
      specific amount of mercury that can be adsorbed and retained by steel appears to
      be a function of both metallurgical and environmental factors. In general, the
      longer the steel is in contact with a fluid or condensate that contains
      measurable concentrations of elemental mercury, the greater the potential for
      mercury accumulation in that steel. Most mercury compounds are thermally unstable
      at elevated temperatures (i.e., above 350  degrees C). As such, the mercury
      associated with impacted scrap is expected to be volatilized out of the metal
      when it is heated during processing (e.g., shredding or torch cutting) or melted
      in a furnace. This release of fugitive gas (Hg vapor) and particulates, as well
      as Hg-impacted bag-house dust and control filters, could potentially pose an
      occupational exposure risk to workers at a scrap metal processing facility. Thus,
      identifying and characterizing the key sources of Hg-impacted scrap, and
      understanding the nature and extent of associated releases, represent a practical
      research need that is essential for improving the environmental management of Hg
      impacted scrap and assessing measures to protect workers from potential health
      and safety hazards that might be posed by mercury and Hg-impacted scrap. 

PMID- 26197425
TI  - Comparing the dynamic performance of wastewater treatment systems: A metafrontier
      Malmquist productivity index approach.
AB  - The assessment of productivity change of wastewater treatment plants (WWTPs) is
      essential to improve the performance over time of the facilities evaluated. This
      study assessed and compared the productivity growth of WWTPs operating with non
      homogeneous technologies. The metafrontier Malmquist productivity index (MMPI)
      was computed for a sample of 99 WWTPs encompassing 4 alternative technologies:
      activated sludge (AS), aerated lagoon (AL), trickling filter (TF) and rotating
      biological contactor (BD). The results indicated that, on average, WWTPs with AS
      and BD exhibited better performance over time than WWTPs with AL and TF. The MMPI
      indicates that, over the period 2007-2009, the productivity rose by 0.9% and 0.3%
      for AS and BD technologies, respectively, whilst for the AL and TF processes, the
      productivity decreased by 0.5% and 2.2%, respectively. The decomposition of the
      MMPI into efficiency change (EC) and technical change (TC) illustrated that EC
      was a positive driver of productivity change for WWTPs that use AS, whilst TC
      contributed positively to the productivity growth of WWTPs using AL and BD.
      Several policy implications to help managers make informed decisions were drawn
      from our empirical analysis. 

PMID- 26197426
TI  - Pig manure treatment and purification by filtration.
AB  - This study aimed to develop a new, complex pig manure treatment and filtration
      process. The final scheme, called the AMAK process, comprised the following
      successive steps: mineralization with mineral acids, alkalization with lime milk,
      superphosphate addition, a second alkalization, thermal treatment, and pressure
      filtration. The proposed method produced a filtrate with 95%, 80%, and 96%
      reductions in chemical oxygen demand, nitrogen content, and phosphorus content,
      respectively. An advantage of the proposed method was that it incorporated a
      crystalline phase into the solid organic part of the manure, which enabled high
      filtration rates (>1000 kg m(-2) h(-1)) and efficient separation. The process
      also eliminated odor emissions from the filtrate and sediment. The treated
      filtrate could be used to irrigate crops or it could be further treated in
      conventional biological wastewater treatment plants. The sediment could be used
      for producing mineral-organic fertilizer. The AMAK process is inexpensive, and it
      requires low investment costs. 

PMID- 26197427
TI  - An environmental generalised Luenberger-Hicks-Moorsteen productivity indicator
      and an environmental generalised Hicks-Moorsteen productivity index.
AB  - The purpose of this paper is to introduce an environmental generalised
      productivity indicator and its ratio-based counterpart. The innovative
      environmental generalised total factor productivity measures inherit the basic
      structure of both Hicks-Moorsteen productivity index and Luenberger-Hicks
      Moorsteen productivity indicator. This methodological contribution shows that
      these new environmental generalised total factor productivity measures yield the
      earlier standard Hicks-Moorsteen index and Luenberger-Hicks-Moorsteen indicator,
      as well as environmental performance index, as special cases. 

PMID- 26197428
TI  - Population Difference in the Associations of KLOTH Promoter Methylation with Mild
      Cognitive Impairment in Xinjiang Uygur and Han Populations.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is the intermediate stage of the
      cognitive changes between normal aging and dementia. KLOTH is an age-related gene
      that may contribute to the risk of MCI. The aim of our study was to explore the
      association between KLOTHO promoter methylation and MCI in Xinjiang Uygur and Han
      populations. METHODS: DNA methylation assay was performed using the bisulphite
      pyrosequencing technology among 96 Uygur (48 MCI and 48 controls) and 96 Han (48
      MCI and 48 controls) Chinese individuals from Xinjiang province of China.
      RESULTS: We found significant association between KLOTHO promoter methylation and
      MCI in the Han Chinese (CpG1: p = 3.77E-06; CpG2: p = 1.91E-07; CpG3: p = 5.83E
      07; CpG4: p = 2.23E-05; CpG5: p = 3.03E-06) but not in the Uygur Chinese. Higher
      KLOTHO promoter methylation levels were found in Han MCI patients than Uygur MCI
      patients for all the five CpGs (adjusted p values by age < 0.02). CONCLUSION: Our
      results showed that KLOTHO promoter hypermethylation contributed to the MCI risk
      in Xinjiang Han Chinese but not in Xinjiang Uygur Chinese. The population
      difference of KLOTHO methylation in the risk of MCI required further
      investigation in the future.

PMID- 26197429
TI  - Ancestry, admixture and fitness in Colombian genomes.
AB  - The human dimension of the Columbian Exchange entailed substantial genetic
      admixture between ancestral source populations from Africa, the Americas and
      Europe, which had evolved separately for many thousands of years. We sought to
      address the implications of the creation of admixed American genomes, containing
      novel allelic combinations, for human health and fitness via analysis of an
      admixed Colombian population from Medellin. Colombian genomes from Medellin show
      a wide range of three-way admixture contributions from ancestral source
      populations. The primary ancestry component for the population is European
      (average = 74.6%, range = 45.0%-96.7%), followed by Native American (average =
      18.1%, range = 2.1%-33.3%) and African (average = 7.3%, range = 0.2%-38.6%).
      Locus-specific patterns of ancestry were evaluated to search for genomic regions
      that are enriched across the population for particular ancestry contributions.
      Adaptive and innate immune system related genes and pathways are particularly
      over-represented among ancestry-enriched segments, including genes (HLA-B and
      MAPK10) that are involved in defense against endemic pathogens such as malaria.
      Genes that encode functions related to skin pigmentation (SCL4A5) and cutaneous
      glands (EDAR) are also found in regions with anomalous ancestry patterns. These
      results suggest the possibility that ancestry-specific loci were differentially
      retained in the modern admixed Colombian population based on their utility in the
      New World environment. 

PMID- 26197430
TI  - Intermittent inhaled corticosteroid therapy versus placebo for persistent asthma
      in children and adults.
AB  - BACKGROUND: International guidelines advocate using daily inhaled corticosteroids
      (ICS) in the management of children and adults with persistent asthma. However,
      in real world clinical settings, these medicines are often used at irregular
      intervals by patients. Recent evidence suggests that the use of intermittent ICS,
      with treatment initiated at the time of early symptoms, may still have benefits
      for reducing the severity of an asthma exacerbation. OBJECTIVES: To compare the
      efficacy and safety of intermittent ICS versus placebo in the management of
      children and adults diagnosed with, or suspected to have, symptoms of mild
      persistent asthma. SEARCH METHODS: We searched the Cochrane Airways Group
      Specialised Register of trials (CAGR), the ClinicalTrials.gov website and the
      World Health Organization (WHO) trials portal in March 2015. SELECTION CRITERIA:
      We included randomised controlled trials (RCTs) that compared intermittent ICS
      versus placebo in children and adults with symptoms of persistent asthma. No co
      interventions were permitted other than rescue relievers and oral corticosteroids
      used during exacerbations. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trials for inclusion, methodological quality and extracted
      data. The primary efficacy outcome was the risk of asthma exacerbations requiring
      oral corticosteroids and the primary safety outcome was serious adverse health
      events. Secondary outcomes included exacerbations, lung function tests, asthma
      control, adverse effects, and withdrawal rates. Quality of the evidence was
      assessed using the GRADE criteria. MAIN RESULTS: Six trials (representing 490
      preschool children, 145 school-aged children and 240 adults) met the inclusion
      criteria. Study durations were 12 to 52 weeks. Results for preschool children
      were presented in a separate analysis as this represents a distinct clinical
      condition, not necessarily related to the development of long term asthma.There
      was a reduction in the risk of patients experiencing one or more exacerbations
      requiring oral corticosteroids in older children (145 participants, odds ratio
      (OR) 0.57; 95% confidence interval (CI) 0.29 to 1.12, low quality evidence) and
      adults with asthma (240 participants, OR 0.10; 95% CI 0.01 to 1.95, low quality
      evidence). These analyses were each based on the findings of a single study. No
      group difference was observed in the risk of serious adverse health events (385
      participants; OR 1.00; 95% CI 0.14 to 7.25, moderate quality evidence). Compared
      to the placebo group, there was an insufficient number of participants to make
      firm conclusions whether the intermittent ICS group displayed any reduction in
      the rate of hospitalisations, day time and night time symptoms scores, or adverse
      events. Lung function tests reported by a single study favoured the use of ICS.
      There was no significant group difference in growth rate of children, or overall
      withdrawals.In preschool children with frequent wheezing episodes, the use of
      intermittent ICS at the onset of early symptoms reduced the likelihood of
      requiring rescue oral corticosteroids by half (490 participants; OR: 0.48; 95% CI
      0.31 to 0.73, moderate quality evidence with minimal heterogeneity). Intermittent
      therapy was associated with fewer serious adverse events (439 participants; OR
      0.42; 95% CI 0.17 to 1.02, low quality evidence). There was no significant
      difference in hospitalisations or in a single study measuring parent perceived
      quality of life. However, intermittent therapy was associated with improvements
      in both day time and night time symptoms. There was no increase in the rates of
      withdrawals, and overall and treatment-specific adverse events. AUTHORS'
      CONCLUSIONS: In children and adults with mild persistent asthma, two studies have
      shown that the use of intermittent ICS at the time of exacerbation reduced the
      chances of needing oral corticosteroids by half. This result is statistically
      significant if we assume that the effect size is the same for each study
      population (fixed effects model), but is not statistically significant when using
      a random effects model. However, the paucity of published evidence limits our
      conclusions towards the 'as-needed' use of this medication. The small number of
      studies and participants were the major reasons for downgrading the overall
      quality of the findings. A corresponding result was found in preschool children
      with wheeze. In this age group, an improvement in day time and night time asthma
      symptoms score and parental perceived quality of life of children similarly
      favoured the ICS group. However, there was no statistical difference in
      hospitalisation rates in any group. This treatment was not associated with any
      significant increase in adverse events. There was no growth suppression noted
      with the use of intermittent ICS in either preschool or school-aged children.
      Considering the limited number of available studies, we emphasise the need for
      more randomised controlled studies in order to confirm these findings.

PMID- 26197431
TI  - Correction: Ruminal Transcriptomic Analysis of Grass-Fed and Grain-Fed Angus Beef
      Cattle.

PMID- 26197434
TI  - First report of the concentrations and implications of DDT residues in chicken
      eggs from a malaria-controlled area.
AB  - In malaria-endemic areas, where DDT is still used for vector control by indoor
      residual spraying (IRS), the concentrations of DDT in human blood and breast milk
      are high, and there are indications of human health impacts. To identify the
      possible avenues of exposure reduction, we created the concept of a Total
      Homestead Environment Approach (THEA). THEA characterizes the interactions
      between DDT, humans, and the biota within and around homesteads. One dietary
      route of human exposure and uptake of DDT, namely, chicken egg consumption, has
      to our knowledge never been studied. The SigmaDDT in eggs from a DDT-sprayed
      village ranged between 5200 and 48,000 ng/g wm (wet mass), with a median of
      11,000 ng/g wm. On a lipid mass-basis (lm), the mean SigmaDDT for eggs from the
      sprayed village was 100,000 ng/g lm. The maximum egg concentration observed was
      three orders of magnitude higher than the median. The acceptable daily intake
      (ADI) was not exceeded based on the consumption of three eggs per week for a 60
      kg person. This equates to an intake of 0.089 g DDT per person per year. Chicken
      egg consumption is therefore a possible target for exposure reduction, probably
      best achieved by reducing the DDT concentrations in soils.

PMID- 26197433
TI  - Ultra-broadband and high-responsive photodetectors based on bismuth film at room
      temperature.
AB  - Bismuth (Bi) has undergone researches for dozens of years on account of its
      abundant physics including the remarkably high mobility, exceptional large
      positive magnetoresistance and the coexistence of an insulating interior as well
      as metallic surfaces. Very recently, two-dimensional topologically-protected
      surface states immune to nonmagnetic perturbation such as surface oxidation and
      impurity scattering were experimentally demonstrated through systematic
      magnetotransport measurements, e.g. weak antilocalization effect and angular
      dependent Shubnikov-de Haas oscillations. Such robust metallic surface states,
      which are efficient in carrier transportation, along with its small bulk gap (14
      meV) make Bi favored for high-responsive broadband photodetection. Here, we for
      the first time demonstrate the stable ultra-broadband photoresponse from 370 nm
      to 1550 nm with good reproducibility at room temperature based on a Bi
      photodetector. The fabricated device's responsivity approaches 250 mA/W,
      accompanied with a rise time of 0.9 s and a decay time of 1.9 s. The photocurrent
      is linear dependent on the voltage and incident power, offering good tunability
      for multi-purpose applications. Thickness-dependent conductance and photocurrent
      reveal that the bulk is the optically active layer while the surface channel is
      responsible for carrier transportation. These findings pave an avenue to develop
      ultra-broadband Bi photodetectors for the next-generation multifunctional
      optoelectronic devices.

PMID- 26197432
TI  - Effects of Iron Overload on the Activity of Na,K-ATPase and Lipid Profile of the
      Human Erythrocyte Membrane.
AB  - Iron is an essential chemical element for human life. However, in some
      pathological conditions, such as hereditary hemochromatosis type 1 (HH1), iron
      overload induces the production of reactive oxygen species that may lead to lipid
      peroxidation and a change in the plasma-membrane lipid profile. In this study, we
      investigated whether iron overload interferes with the Na,K-ATPase activity of
      the plasma membrane by studying erythrocytes that were obtained from the whole
      blood of patients suffering from iron overload. Additionally, we treated
      erythrocytes of normal subjects with 0.8 mM H2O2 and 1 MUM FeCl3 for 24 h. We
      then analyzed the lipid profile, lipid peroxidation and Na,K-ATPase activity of
      plasma membranes derived from these cells. Iron overload was more frequent in men
      (87.5%) than in women and was associated with an increase (446%) in lipid
      peroxidation, as indicated by the amount of the thiobarbituric acid reactive
      substances (TBARS) and an increase (327%) in the Na,K-ATPase activity in the
      plasma membrane of erythrocytes. Erythrocytes treated with 1 MUM FeCl3 for 24 h
      showed an increase (132%) in the Na,K-ATPase activity but no change in the TBARS
      levels. Iron treatment also decreased the cholesterol and phospholipid content of
      the erythrocyte membranes and similar decreases were observed in iron overload
      patients. In contrast, erythrocytes treated with 0.8 mM H2O2 for 24 h showed no
      change in the measured parameters. These results indicate that erythrocytes from
      patients with iron overload exhibit higher Na,K-ATPase activity compared with
      normal subjects and that this effect is specifically associated with altered iron
      levels. 

PMID- 26197435
TI  - Development and validation of a sensitive LC-MS/MS assay for the quantification
      of nizatidine in human plasma and urine and its application to pharmacokinetic
      study.
AB  - We developed and validated a high performance liquid chromatographic method
      coupled with triple quadrupole mass spectrometry for analysis of nizatidine in
      human plasma and urine. The biological samples were precipitated with methanol
      before separation on an Agilent Eclipse Plus C18 column (100mm*46mm, 5MUm) with a
      mixture of methanol and water (95:5, plus 5mM ammonium formate) as the mobile
      phase at 0.5mL/min. Detection was performed using multiple reaction monitoring
      modes via electrospray ionization (ESI) at m/z 332.1->155.1 (for nizatidine) and
      m/z 335.1->155.1 (for [(2)H3]-nizatidine, the internal standard). The linear
      response range was 5-2000ng/mL and 0.5-80MUg/mL for human plasma and urine, with
      the lower limits of quantification of 5ng/mL and 0.5MUg/mL, respectively. The
      method was validated according to the biological method validation guidelines of
      the Food and Drug Administration and proved acceptable. This newly developed
      analytical method was successfully applied in a pharmacokinetic study following
      single oral administration of a 150mg nizatidine capsule in to 16 healthy Chinese
      subjects. Maximum and endpoint concentrations in plasma and urine were
      quantifiable, suggesting our method is appropriate for routine pharmacokinetic
      analysis. 

PMID- 26197436
TI  - Accurate measurement of the essential micronutrients methionine, homocysteine,
      vitamins B6, B12, B9 and their metabolites in plasma, brain and maternal milk of
      mice using LC/MS ion trap analysis.
AB  - Methionine, homocysteine, vitamins B6, B12, B9, and their metabolites are crucial
      co-factors and substrates for many basic biological pathways including one-carbon
      metabolism, and they are particularly important for brain function and
      development and epigenetic mechanisms. These are essential nutrients that cannot
      be synthesized endogenously and thus need to be taken in via diet. A novel method
      was developed that enables simultaneous assessment of the exact concentrations of
      these essential micronutrients in various matrices, including maternal milk,
      plasma, and brain of neonatal mice. The protocol for analysis of these components
      in the various matrices consists of a cleanup step (i.e. lipid extraction
      followed by protein precipitation) combined with a liquid chromatography mass
      spectrometry (LC/MS) ion trap method with high sensitivity and selectivity (SRM
      mode). This novel method enables the measurement of these essential nutrients
      with good recoveries (69-117%), and high intra-day (<10%) and high intra-day
      precision (defined as <15% for compounds with an isotopologue and <20% for
      compounds without an isotopologue as internal standard) in plasma, maternal milk,
      and brain of mice at low and high levels. In addition, lower limits of
      quantitation (LOQ) were determined for the various matrices in the range for
      methionine (700-2000nmol/L), homocysteine (280-460-nmol/L), vitamins B6 (5
      230nmol/L), B12 (7-11nmol/L), B9 (20-30nmol/L). Degradation of vitamins and
      oxidation of homocysteine is limited to a minimum, and only small sample volumes
      (30MUL plasma, 20mg brain and maternal milk) are needed for simultaneous
      measurement. This method can help to understand how these nutrients are
      transferred from mother to offspring via maternal milk, as well as how these
      nutrients are absorbed by the offspring and eventually taken up in various
      tissues amongst the brain in preclinical and clinical research settings.
      Therefore the method can help to explore critical periods in lactating mothers
      and developing offspring. 

PMID- 26197438
TI  - Bicoid signal extraction with a selection of parametric and nonparametric signal
      processing techniques.
AB  - The maternal segmentation coordinate gene bicoid plays a significant role during
      Drosophila embryogenesis. The gradient of Bicoid, the protein encoded by this
      gene, determines most aspects of head and thorax development. This paper seeks to
      explore the applicability of a variety of signal processing techniques at
      extracting bicoid expression signal, and whether these methods can outperform the
      current model. We evaluate the use of six different powerful and widely-used
      models representing both parametric and nonparametric signal processing
      techniques to determine the most efficient method for signal extraction in
      bicoid. The results are evaluated using both real and simulated data. Our
      findings show that the Singular Spectrum Analysis technique proposed in this
      paper outperforms the synthesis diffusion degradation model for filtering the
      noisy protein profile of bicoid whilst the exponential smoothing technique was
      found to be the next best alternative followed by the autoregressive integrated
      moving average. 

PMID- 26197439
TI  - A Network of Networks Perspective on Global Trade.
AB  - Mutually intertwined supply chains in contemporary economy result in a complex
      network of trade relationships with a highly non-trivial topology that varies
      with time. In order to understand the complex interrelationships among different
      countries and economic sectors, as well as their dynamics, a holistic view on the
      underlying structural properties of this network is necessary. This study employs
      multi-regional input-output data to decompose 186 national economies into 26
      industry sectors and utilizes the approach of interdependent networks to analyze
      the substructure of the resulting international trade network for the years 1990
      2011. The partition of the network into national economies is observed to be
      compatible with the notion of communities in the sense of complex network theory.
      By studying internal versus cross-subgraph contributions to established complex
      network metrics, new insights into the architecture of global trade are obtained,
      which allow to identify key elements of global economy. Specifically, financial
      services and business activities dominate domestic trade whereas electrical and
      machinery industries dominate foreign trade. In order to further specify each
      national sector's role individually, (cross-)clustering coefficients and cross
      betweenness are obtained for different pairs of subgraphs. The corresponding
      analysis reveals that specific industrial sectors tend to favor distinct
      directionality patterns and that the cross-clustering coefficient for
      geographically close country pairs is remarkably high, indicating that spatial
      factors are still of paramount importance for the organization of trade patterns
      in modern economy. Regarding the evolution of the trade network's substructure,
      globalization is well-expressed by trends of several structural characteristics
      (e.g., link density and node strength) in the interacting network framework.
      Extreme events, such as the financial crisis 2008/2009, are manifested as
      anomalies superimposed to these trends. The marked reorganization of trade
      patterns, associated with this economic crisis in comparison to "normal" annual
      fluctuations in the network structure is traced and quantified by a new widely
      applicable generalization of the Hamming distance to weighted networks.

PMID- 26197437
TI  - Sphingosine 1 Phosphate at the Blood Brain Barrier: Can the Modulation of S1P
      Receptor 1 Influence the Response of Endothelial Cells and Astrocytes to
      Inflammatory Stimuli?
AB  - The ability of the Blood Brain Barrier (BBB) to maintain proper barrier
      functions, keeping an optimal environment for central nervous system (CNS)
      activity and regulating leukocytes' access, can be affected in CNS diseases.
      Endothelial cells and astrocytes are the principal BBB cellular constituents and
      their interaction is essential to maintain its function. Both endothelial cells
      and astrocytes express the receptors for the bioactive sphingolipid S1P.
      Fingolimod, an immune modulatory drug whose structure is similar to S1P, has been
      approved for treatment in multiple sclerosis (MS): fingolimod reduces the rate of
      MS relapses by preventing leukocyte egress from the lymph nodes. Here, we
      examined the ability of S1P and fingolimod to act on the BBB, using an in vitro
      co-culture model that allowed us to investigate the effects of S1P on endothelial
      cells, astrocytes, and interactions between the two. Acting selectively on
      endothelial cells, S1P receptor signaling reduced cell death induced by
      inflammatory cytokines. When acting on astrocytes, fingolimod treatment induced
      the release of a factor, granulocyte macrophage colony-stimulating factor (GM
      CSF) that reduced the effects of cytokines on endothelium. In an in vitro BBB
      model incorporating shear stress, S1P receptor modulation reduced leukocyte
      migration across the endothelial barrier, indicating a novel mechanism that might
      contribute to fingolimod efficacy in MS treatment.

PMID- 26197440
TI  - Seroprevalence of antibody to TgGRA7 antigen of Toxoplasma gondii in livestock
      animals from Western Java, Indonesia.
AB  - Toxoplasmosis is a concern in both human and veterinary medicine, and the
      consumption of undercooked meat infected with Toxoplasma gondii is a major risk
      factor in human infection. Establishing the prevalence of the parasite in food
      producing livestock is essential to reduce the risk of human infection. This
      study aimed to determine the prevalence of T. gondii-specific antibodies in
      cattle and pigs in Western Java, Indonesia. Serum samples from 598 cattle and 205
      pigs from 18 locations in Western Java, Indonesia, were tested for antibodies to
      T. gondii using an enzyme-linked immunosorbent assay (ELISA). The seroprevalence
      was 14.6% in pigs and 7.4% in cattle, and significantly more pigs were
      seropositive compared with cattle (p<0.01). The results of this study suggest
      that consumption of undercooked meat should be regarded as an important source of
      infection in people. This study suggests that the risk factors for T. gondii
      infection in livestock appeared to be different in each location because
      geographical variation in seroprevalence was observed. The results of this study
      will facilitate further research to identify and control risk factors for T.
      gondii in the surveyed locations. 

PMID- 26197442
TI  - Evolved psychology in a novel environment : Male macaques and the "seniority
      rule".
AB  - The human "environment of evolutionary adaptedness" can only be inferred
      indirectly. In contrast, the behavior of some nonhuman animals can be compared
      among "natural" and various altered environments. As an example, male immigration
      tactics in unprovisioned versus provisioned macaque (Macaca) populations are
      compared using Tooby and Cosmides's (1992) framework for evolutionary functional
      analysis. In unprovisioned populations, social groups contain few males, and
      immigrant male takeovers of alpha rank occur frequently. In provisioned
      populations, groups contain many males, and males almost invariably enter social
      groups at very low rank and rise in rank only as more dominant males emigrate or
      die. Male conformity to the "seniority rule" is hypothesized to represent the
      behavioral output of an evolved decision-making algorithm (psychological
      mechanism) that takes into account (1) the net payoff of each rank in the
      dominance hierarchy and (2) the power of male group size as a predictor of the
      likelihood of successful immigrant takeover. 

PMID- 26197443
TI  - Brothers and sisters : How sibling interactions affect optimal parental
      allocations.
AB  - Data from the Kipsigis of Kenya are used to test two models for how parents
      invest in offspring, the Trivers-Willard and local resource
      competition/enhancement hypotheses. Investment is measured as age-specific
      survival, educational success, marital arrangements, and some components of
      property inheritance, permitting an evaluation of how biases persist or alter
      over the period of dependence. Changes through time in such biases are also
      examined. Despite stronger effects of wealth on the reproductive success of men
      than women, the survival of sons and daughters is not related to parental wealth.
      However, a Trivers-Willard effect characterizes educational investment: poor
      families show a greater concern for daughters' (vis-a-vis sons') schooling than
      do rich families, a trend that has increased over time. In regard to models of
      local resource competition and enhancement, men's reproductive success decreases
      with number of brothers and increases with number of sisters; this pattern of
      competition with same-sex sibs and cooperation with opposite-sex sibs is not
      found among women. As predicted from these observations, parents show reduced
      investment in sons with a large number of brothers, and increased investment in
      sons with a large number of sisters. By contrast, investment in daughters is
      entirely unaffected by number of sisters and is influenced only in subtle ways by
      number of brothers. Levels of investment in relation to sibship size
      (irrespective of siblings' sex) are highest for younger children of large sib
      sets.Discussion of the results in relation to those from other studies leads to
      three conclusions. First, predictive models for how investment biases vary across
      societies must consider a broad range of socioecological factors constraining
      parental options and payoffs. Second, the timing of investment biases within
      societies will be affected by the value of children and the costs of parental
      investment. Third, measures of investment appropriate for between-sex and between
      class comparisons need careful attention. Each of these issues is brought to bear
      on the question of why, in contrast to so many other parts of the world, sex
      preferences are so muted in Africa. 

PMID- 26197444
TI  - Bargaining theory and cooperative fishing participation on ifaluk atoll.
AB  - In this paper we examine the merit of bargaining theory, in its economic and
      ecological forms, as a model for understanding variation in the frequency of
      participation in cooperative fishing among men of Ifaluk atoll in Micronesia. Two
      determinants of bargaining power are considered: resource control and a
      bargainer's utility gain for his expected share of the negotiated resource.
      Several hypotheses which relte cultural and life-course parameters to bargaining
      power are tested against data on the frequency of cooperative sail-fishing
      participation. Consistent with predictions generated from bargaining theory, we
      show that (1) age is negatively correlated with cooperative fishing
      participation, (2) men of highranking clans and men with high levels of education
      fish less than men of low-ranking clans and less-educated men, (3) men with high
      expected utility gains from fishing returns fish more than men with low expected
      utility gains, (4) number of dependents is positively correlated with cooperative
      fishing participation, and (5) the number of young genetic offspring residing
      with a man is positively correlated with cooperative fishing participation,
      whereas the number of genetic offspring more than 13 years old who are residing
      with a man is negatively correlated with cooperative fishing participation. 

PMID- 26197441
TI  - A Novel Locus Harbouring a Functional CD164 Nonsense Mutation Identified in a
      Large Danish Family with Nonsyndromic Hearing Impairment.
AB  - Nonsyndromic hearing impairment (NSHI) is a highly heterogeneous condition with
      more than eighty known causative genes. However, in the clinical setting, a large
      number of NSHI families have unexplained etiology, suggesting that there are many
      more genes to be identified. In this study we used SNP-based linkage analysis and
      follow up microsatellite markers to identify a novel locus (DFNA66) on chromosome
      6q15-21 (LOD 5.1) in a large Danish family with dominantly inherited NSHI. By
      locus specific capture and next-generation sequencing, we identified a c.574C>T
      heterozygous nonsense mutation (p.R192*) in CD164. This gene encodes a 197 amino
      acid transmembrane sialomucin (known as endolyn, MUC-24 or CD164), which is
      widely expressed and involved in cell adhesion and migration. The mutation
      segregated with the phenotype and was absent in 1200 Danish control individuals
      and in databases with whole-genome and exome sequence data. The predicted effect
      of the mutation was a truncation of the last six C-terminal residues of the
      cytoplasmic tail of CD164, including a highly conserved canonical sorting motif
      (YXXF). In whole blood from an affected individual, we found by RT-PCR both the
      wild-type and the mutated transcript suggesting that the mutant transcript
      escapes nonsense mediated decay. Functional studies in HEK cells demonstrated
      that the truncated protein was almost completely retained on the plasma cell
      membrane in contrast to the wild-type protein, which targeted primarily to the
      endo-lysosomal compartments, implicating failed endocytosis as a possible disease
      mechanism. In the mouse ear, we found CD164 expressed in the inner and outer hair
      cells of the organ of Corti, as well as in other locations in the cochlear duct.
      In conclusion, we have identified a new DFNA locus located on chromosome 6q15-21
      and implicated CD164 as a novel gene for hearing impairment. 

PMID- 26197445
TI  - How maya women respond to changing technology : The effect of helping behavior on
      initiating reproduction.
AB  - In the mid 1970s labor-saving technology was introduced into a Maya subsistence
      agricultural community that markedly increased the efficiency with which maize
      could be ground and water collected. This increased efficiency introduces a
      possible savings in the time that women allocate to work, which can be
      reapportioned to child care, food production, domestic work, or leisure. An
      earlier study suggested that this labor-saving technology had a positive effect
      in decreasing the age at which these Maya women begin their reproductive careers.
      Although there is a statistical association between the age at which women bear
      their first child and the introduction of modern technology, this association
      does not demonstrate that the decline in age at first birth is causally related
      to the presence of technology. This paper pursues two objectives to evaluate this
      potential causal relationship in greater detail. First, a theory relating
      technological change to the initiation of a reproductive career is briefly
      developed in order to make qualitative predictions about behavioral changes as a
      response to changing technology. Second, these predictions are then tested
      against time allocation data recently collected in this same Maya community.We
      suggest that both of the conditions necessary to initiate reproduction-fecundity
      and access to mates-fundamentally depend on the amount of help that a girl
      provides to her family. Further, the help that a girl provides can be affected by
      technological changes. Analyses show that when modern technology is available,
      unmarried young women do not change the time allocated to domestic tasks and
      child care, and allocate more time to low-energy leisure activities. This lack of
      perceived benefit to working more and a potential concomitant shift towards a
      positive energy balance may in part explain why Maya women leave home and
      initiate reproduction at a younger age after labor-saving technology is
      introduced. 

PMID- 26197446
TI  - Silent Crohn's Disease: Asymptomatic Patients with Elevated C-reactive Protein
      Are at Risk for Subsequent Hospitalization.
AB  - BACKGROUND: Patient-reported Crohn's disease (CD) symptoms and endoscopic
      evaluation have historically guided routine care, but the risk of complications
      in asymptomatic patients with elevated C-reactive protein (CRP) is unknown.
      METHODS: We conducted a prospective observational cohort study of patients with
      CD from a tertiary care center. Subjects with short inflammatory bowel disease
      questionnaire scores >= 50, Harvey-Bradshaw CD scores <= 4, and same-day CRP
      measurement were eligible for inclusion. The primary outcome was disease-related
      hospitalization up to 24 months after the qualifying clinic visit. We assessed
      the relationship between CRP elevation and subsequent hospitalization. RESULTS:
      There were 351 asymptomatic patients with CD (median age 40 yr; 50.4% female) who
      met inclusion criteria, and CRP was elevated in 19.7% of these individuals (n =
      69). At 24 months, 16.8% (n = 59) of the study population had been hospitalized
      for CD-related complications. Significantly, more patients with an elevated CRP
      were hospitalized (33.3% versus 12.8%, P < 0.0001) compared with those with a
      normal CRP and were hospitalized at increased rate (P < 0.001) on Kaplan-Meier
      analysis. CRP elevation was significantly and independently associated with
      increased risk of hospitalization (adjusted hazard ratio 2.12; 95% confidence
      interval, 1.13-3.98; P = 0.02) in multivariable survival analysis. CONCLUSIONS:
      Asymptomatic patients with CD with elevated CRP are at a nearly 2-fold higher
      risk for hospitalization over the subsequent 2 years compared with asymptomatic
      patients with CD without CRP elevation.

PMID- 26197447
TI  - U.S. Patients with Ulcerative Colitis Do Not Have a Decreased Risk of
      Diverticulosis.
AB  - BACKGROUND: Studies outside the United States have described a lower prevalence
      of diverticulosis in patients with inflammatory bowel disease (IBD) than in
      patients without IBD. The aim of this study was to assess the prevalence of
      diverticulosis and associated risk factors in patients with ulcerative colitis
      (UC) at a U.S. tertiary care center. METHODS: We performed a retrospective review
      of patients over 50 years of age who underwent screening or surveillance
      colonoscopy from January 2006 to December 2013. We first assessed the prevalence
      of diverticulosis in patients with UC compared with patients without IBD. Then,
      we performed a nested case-control study comparing UC patients with
      diverticulosis (cases) with UC patients without diverticulosis (controls).
      RESULTS: We identified 544 patients with UC and 16,705 patients without IBD who
      underwent colonoscopy. On univariate analysis, 23.5% of patients with UC had
      diverticulosis, and 46.7% of patients without IBD had diverticulosis, P < 0.01
      and relative risk = 0.50 (95% CI, 0.43-0.58). Multivariate analysis adjusting for
      age and gender found a relative risk of diverticulosis in UC = 1.02 (95% CI, 1.02
      1.03). In the nested case-control study, there were no differences between UC
      cases and UC controls in disease duration (16.7 versus 18.7 yr; P = 0.27), extent
      of disease (pancolitis 50% versus 60.1%; P = 0.24), obesity (34.5% versus 29.2%;
      P = 0.40), or ethnicity (86.3% white versus 79.8%; P = 0.20). There was a trend
      toward history of smoking in patients with UC and diverticulosis (49.5% versus
      35.5%; P = 0.09). CONCLUSIONS: In this U.S.-based study, patients with UC had a
      slightly increased of diverticulosis compared with patients without IBD
      undergoing screening or surveillance colonoscopy. There were no identified
      predictors for diverticular disease in patients with UC, but there was a trend
      toward previous smoking status and development of diverticulosis. These results
      are different than previously reported data in patients with IBD in other
      countries and may represent unique dietary differences that contribute to the
      development of diverticulosis.

PMID- 26197448
TI  - Serology of Patients with Ulcerative Colitis After Pouch Surgery Is More
      Comparable with that of Patients with Crohn's Disease.
AB  - BACKGROUND: The serologic status of patients with ulcerative colitis (UC) who
      develop postoperative pouchitis was compared with that of patients with Crohn's
      disease (CD) and unoperated patients with UC. METHODS: Pouch patients were
      stratified into normal pouch, acute/recurrent acute pouchitis, and chronic
      pouchitis/Crohn's-like disease of the pouch groups. Antibodies against glycans
      associated with CD (anti-Saccharomyces cerevisiae, anti-laminaribioside, anti
      chitobioside, and anti-mannobioside carbohydrate antibodies [ASCA, ALCA, ACCA,
      and AMCA, respectively]) were detected and correlated with type of inflammatory
      bowel disease and pouch behavior. RESULTS: A total of 501 patients with
      inflammatory bowel diseases were recruited: 250 (50%) CD, 124 (24.7%) unoperated
      UC, and 127 (25.3%) UC-pouch. At least 1 positive antibody was detected in 77.6%
      CD, 52.0% UC-pouch and 33.1% unoperated UC (P < 0.0001 for all). ACCA and AMCA
      prevalence in CD, UC-pouch and unoperated patients with UC were 33.2%, 24.4%, and
      16.9% (P = 0.003 for all) and 35.2%, 26.8%, and 7.3%, respectively (P < 0.0001
      for all). ALCA and ASCA were more prevalent in patients with CD than unoperated
      UC and UC-pouch patients. A longer interval since pouch surgery was associated
      with inflammatory pouch behavior: 12.45, 11.39, and 8.5 years for acute/recurrent
      acute pouchitis, chronic pouchitis/Crohn's-like disease of the pouch, and normal
      pouch, respectively, P = 0.01 for all. CONCLUSIONS: The prevalence of the CD
      associated anti-glycan antibodies ACCA and AMCA is significantly increased in UC
      pouch patients, suggesting that pouch surgery may trigger differential immune
      responses to glycans. The finding that the serology of UC-pouch patients shares
      similarities with that of patients with CD supports the notion that those 2
      inflammatory bowel diseases share a common pathogenic pathway.

PMID- 26197449
TI  - Capsule Endoscopy: Diagnostic Accuracy of Lewis Score in Patients with Suspected
      Crohn's Disease.
AB  - BACKGROUND: The Lewis Score (LS) aims to standardize the method of quantification
      of small bowel inflammatory activity detected by the small bowel capsule
      endoscopy (SBCE). The aim of this study was to evaluate the diagnostic accuracy
      of the LS in patients with suspected CD undergoing SBCE. METHODS: We performed a
      retrospective study including patients who underwent SBCE for suspected CD
      between September 2006 and February 2013. Patients were grouped according to the
      criteria of the International Conference on Capsule Endoscopy for the definition
      of suspected CD. Inflammatory activity on SBCE was objectively assessed by
      determining the LS. RESULTS: Ninety-five patients were included. Group 1: 37
      patients not fulfilling International Conference on Capsule Endoscopy criteria;
      Group 2: 58 patients with >= 2 International Conference on Capsule Endoscopy
      criteria. The diagnosis of CD was established in 38 patients (40%): 8 (21.6%)
      from group 1 and 30 from group 2 (51.7%) (P = 0.003). Among those patients, 34
      had LS >= 135 (73.9%) and 4 had LS <135 (8.2%) at SBCE (P < 0.001). The LS >= 135
      had an overall diagnostic accuracy of 83.2% with a sensitivity, specificity,
      positive predictive value, and negative predictive value for the diagnosis of CD
      of 89.5%, 78.9%, 73.9%, and 91.8%, respectively. CONCLUSIONS: The application of
      LS >= 135 as the cutoff value for the presence of significant inflammatory
      activity in patients undergoing SBCE for suspected CD may be useful to establish
      the diagnosis of CD. In patients with LS < 135, the probability of having CD
      confirmed on follow-up is low.

PMID- 26197450
TI  - Antiviral Therapy in Steroid-refractory Ulcerative Colitis with Cytomegalovirus:
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: The role of antiviral therapy in patients with ulcerative colitis
      (UC) with cytomegalovirus (CMV) remains unclear. We therefore performed a
      systematic review and meta-analysis to assess the association between antiviral
      therapy and the risk of colectomy. METHODS: Multiple electronic databases were
      searched systematically through July 2014 for studies reporting the risk of
      colectomy in patients with UC with CMV stratified by treatment with antiviral
      agents. Colectomy rates were assessed for the overall cohort and stratified by
      corticosteroid (CS) refractoriness. We estimated summary odds ratios and 95%
      confidence intervals, using random-effects model, and used Grading of
      Recommendations Assessment, Development, and Evaluation criteria to appraise the
      quality of evidence. RESULTS: Fifteen observational studies (333 patients with UC
      with CMV, 43.2% treated with antiviral agents) were identified, of which 8
      stratified patients according to CS-refractory disease (55.4% treated with
      antiviral agents). Antiviral therapy resulted in a significantly lower risk of
      colectomy in patients with CS-refractory disease (odds ratio, 0.20; 95%
      confidence interval, 0.08-0.49; I = 0%) but not in the overall population of
      patients with UC (odds ratio, 0.92; 95% confidence interval, 0.31-2.76; I = 65).
      The quality evidence was low. The results were stable when restricting the
      analysis to patients with a tissue diagnosis of CMV and studies that defined CS
      refractory disease as a failure to respond to intravenous CS. CONCLUSIONS:
      Antiviral therapy may benefit a subgroup of patients with UC who are refractory
      to CS. Further prospective trials are required to confirm these findings.

PMID- 26197451
TI  - Safety and Efficacy of an Oral Inhibitor of the Purinergic Receptor P2X7 in Adult
      Patients with Moderately to Severely Active Crohn's Disease: A Randomized Placebo
      controlled, Double-blind, Phase IIa Study.
AB  - BACKGROUND: AZD9056 is a selective orally active inhibitor of the purinergic
      receptor P2X7, which is a key player in the generation and secretion of several
      proinflammatory cytokines involved in the pathogenesis of Crohn's disease (CD).
      The aim of this phase IIa study was to assess the efficacy and safety of AZD9056
      for the treatment of moderately to severely active CD. METHODS: We conducted a
      placebo-controlled, multicenter, double-blind phase IIa study in patients with
      moderately to severely active CD as defined by a CD Activity Index (CDAI) of at
      least 220. Patients were randomized in a 2:1 mode either to 200 mg of AZD9056
      administered orally as a tablet once daily for 28 days or matching placebo.
      Primary endpoint was the change in CDAI from baseline at day 28, and secondary
      endpoints included clinical remission (CDAI < 150) and CDAI 70 response and
      improvement in the quality of life measures Short Form 36 and Inflammatory Bowel
      Disease Questionnaire. Changes in serum C-reactive protein and fecal calprotectin
      were assessed. RESULTS: In total, 34 patients were enrolled, 24 to AZD9056 and 10
      to placebo. The CDAI dropped in AZD9056-treated subjects from a baseline mean of
      311 to 242 and from 262 to 239 in placebo-treated subjects (P = 0.049). Remission
      and response rates were numerically higher with AZD9056 versus placebo, (n = 5,
      24% versus n = 1, 11%, P = 0.43 and n = 11, 52% versus n = 2, 22%, P = 0.13,
      respectively). Marked decrease in disease activity was observed for the CDAI
      subcomponents, pain and general well-being. Apart from a statistically
      significant improvement in the Mental Component Score of Short Form 36 for
      AZD9056 versus placebo (P = 0.017), no other differences in measurements of
      quality of life could be observed. There was no decrease in concentrations of
      serum C-reactive protein and fecal calprotectin during treatment. AZD9056 was
      well-tolerated, and no serious adverse events were reported. CONCLUSIONS: Our
      data suggest that the purinergic receptor P2X7 antagonist AZD9056 has the
      potential to improve symptoms in patients with moderate-to-severe CD combined
      with a beneficial risk profile. Although the lack in change of inflammatory
      biomarkers questions its anti-inflammatory potential, the results obtained in
      this study rather suggest P2X7 antagonism for the treatment of chronic abdominal
      pain.

PMID- 26197452
TI  - Aberrant Niche Signaling in the Etiopathogenesis of Ulcerative Colitis.
AB  - BACKGROUND: Primary colonic epithelial defects leading to inflammatory responses
      are considered central to the development of ulcerative colitis (UC). However, a
      systematic analysis of various colonic subcompartments in the pathogenesis of UC
      before inflammation remains elusive. Here, we explored changes in colonic
      subcompartments and their associated niche signals in patient mucosal biopsies
      and in an animal model of colitis. METHODS: Analysis of mucosal biopsies obtained
      from uninvolved and involved regions of patients with UC and Crohn's disease was
      performed and compared with normal subjects. Temporal analysis of colonic
      subcompartments was performed in mice administered with 5% dextran sodium
      sulphate. Phenotypic enumeration of the crypt subcompartment was complemented
      with flow cytometric analysis. Members of Notch and Wnt signaling pathways were
      analyzed by molecular, biochemical, and colocalization studies. RESULTS:
      Phenotypic enumeration of colonocytes' subcompartments from patients revealed
      significant alterations of the lower crypt, enriched in stem cell and
      progenitors, independent of inflammation. These changes, unique to UC, were
      confirmed by immunohistochemistry and molecular analysis. In parallel, a defect
      in proliferation and Muc2 synthesis was observed. Animal data before inflammation
      recapitulated human studies. Mechanistic studies revealed that changes in
      signaling through Wnt primarily affected colonic stem cells, whereas Notch
      affected progenitor function. CONCLUSIONS: Our results thus provide new insights
      into the development of inflammation and relapse in UC and suggest that the stem
      cell niche in the colon may influence pathogenesis of the disease.

PMID- 26197453
TI  - Antrum Mucosal Protein-18 Peptide Targets Tight Junctions to Protect and Heal
      Barrier Structure and Function in Models of Inflammatory Bowel Disease.
AB  - BACKGROUND: A peptide derived from Antrum Mucosal Protein (AMP)-18 (gastrokine-1)
      reduces the extent of mucosal erosions and clinical severity in mice with dextran
      sulfate sodium-induced colonic injury. This study set out to determine if AMP
      peptide was also therapeutic for immune- and cytokine-mediated mouse models of
      intestinal injury and inflammatory bowel diseases by enhancing and stabilizing
      tight junctions. METHODS: Therapeutic effects of AMP peptide were examined in
      interleukin-10-deficient and a T-cell adoptive transfer models of colitis in
      immunodeficient recombinase activating gene-1 knock-out (RAG-1-/-) mice.
      Mechanisms by which AMP peptide enhances barrier function and structure were
      studied ex vivo using intestine and colon from mice given lipopolysaccharide and
      in AMP-18-deficient mice given dextran sulfate sodium. RESULTS: In interleukin-10
      deficient mice given piroxicam, AMP peptide enhanced recovery after weight loss,
      protected against colon shortening and segmental dilation, and reduced the
      colitis activity score. In the T-cell transfer model, treatment with the peptide
      protected against colon shortening. In mice given lipopolysaccharide in vivo to
      induce gut injury, AMP peptide prevented the onset of, and reversed established
      intestinal hyperpermeability by targeting TJ proteins and perijunctional actin.
      AMP-18-deficient mice challenged with dextran sulfate sodium exhibited increased
      mortality, developed erosions in the colon, and had lower levels of ZO-1 in TJs
      than heterozygous littermates or wild-type mice. CONCLUSIONS: The results
      indicate that AMP-18/peptide may serve a protective role against injury along the
      gastrointestinal mucosal barrier, and recommend further development of AMP
      peptide as a novel agent to treat patients with inflammatory bowel disease.

PMID- 26197454
TI  - Large-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal
      Human Aging.
AB  - While many age-associated immune changes have been reported, a comprehensive set
      of metrics of immune aging is lacking. Here we report data from 243 healthy
      adults aged 40-97, for whom we measured clinical and functional parameters, serum
      cytokines, cytokines and gene expression in stimulated and unstimulated PBMC,
      PBMC phenotypes, and cytokine-stimulated pSTAT signaling in whole blood. Although
      highly heterogeneous across individuals, many of these assays revealed trends by
      age, sex, and CMV status, to greater or lesser degrees. Age, then sex and CMV
      status, showed the greatest impact on the immune system, as measured by the
      percentage of assay readouts with significant differences. An elastic net
      regression model could optimally predict age with 14 analytes from different
      assays. This reinforces the importance of multivariate analysis for defining a
      healthy immune system. These data provide a reference for others measuring immune
      parameters in older people.

PMID- 26197456
TI  - Intraspecific Variation among Social Insect Colonies: Persistent Regional and
      Colony-Level Differences in Fire Ant Foraging Behavior.
AB  - Individuals vary within a species in many ecologically important ways, but the
      causes and consequences of such variation are often poorly understood. Foraging
      behavior is among the most profitable and risky activities in which organisms
      engage and is expected to be under strong selection. Among social insects there
      is evidence that within-colony variation in traits such as foraging behavior can
      increase colony fitness, but variation between colonies and the potential
      consequences of such variation are poorly documented. In this study, we tested
      natural populations of the red imported fire ant, Solenopsis invicta, for the
      existence of colony and regional variation in foraging behavior and tested the
      persistence of this variation over time and across foraging habitats. We also
      reared single-lineage colonies in standardized environments to explore the
      contribution of colony lineage. Fire ants from natural populations exhibited
      significant and persistent colony and regional-level variation in foraging
      behaviors such as extra-nest activity, exploration, and discovery of and
      recruitment to resources. Moreover, colony-level variation in extra-nest activity
      was significantly correlated with colony growth, suggesting that this variation
      has fitness consequences. Lineage of the colony had a significant effect on extra
      nest activity and exploratory activity and explained approximately half of the
      variation observed in foraging behaviors, suggesting a heritable component to
      colony-level variation in behavior.

PMID- 26197455
TI  - CCR4 Controls the Suppressive Effects of Regulatory T Cells on Early and Late
      Events during Severe Sepsis.
AB  - Sepsis is a deadly disease characterized by an overwhelming release of
      inflammatory mediators and the activation of different types of cells. This
      altered state of cell activation, termed leukocyte reprogramming, contributes to
      patient outcome. However, the understanding of the process underlying sepsis and
      the role of regulatory T cells (Tregs) in sepsis remains to be elucidated. In
      this study, we investigated the role of CCR4, the CCL17/CCL22 chemokine receptor,
      in the innate and acquired immune responses during severe sepsis and the role of
      Tregs in effecting the outcome. In contrast with wild-type (WT) mice subjected to
      cecal ligation and puncture (CLP) sepsis, CCR4-deficient (CCR4-/-) septic mice
      presented an increased survival rate, significant neutrophil migration toward the
      infection site, a low bacterial count in the peritoneum, and reduced lung
      inflammation and serum cytokine levels. Thus, a better early host response may
      favor an adequate long-term response. Consequently, the CCR4-/- septic mice were
      not susceptible to secondary fungal infection, in contrast with the WT septic
      mice. Furthermore, Tregs cells from the CCR4-/- septic mice showed reduced
      suppressive effects on neutrophil migration (both in vivo and in vitro),
      lymphocyte proliferation and ROS production from activated neutrophils, in
      contrast with what was observed for Tregs from the WT septic mice. These data
      show that CCR4 is involved in immunosuppression after severe sepsis and suggest
      that CCR4+ Tregs negatively modulate the short and long-term immune responses.

PMID- 26197457
TI  - Latent KSHV Infected Endothelial Cells Are Glutamine Addicted and Require
      Glutaminolysis for Survival.
AB  - Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of Kaposi's
      Sarcoma (KS). KSHV establishes a predominantly latent infection in the main KS
      tumor cell type, the spindle cell, which is of endothelial cell origin. KSHV
      requires the induction of multiple metabolic pathways, including glycolysis and
      fatty acid synthesis, for the survival of latently infected endothelial cells.
      Here we demonstrate that latent KSHV infection leads to increased levels of
      intracellular glutamine and enhanced glutamine uptake. Depletion of glutamine
      from the culture media leads to a significant increase in apoptotic cell death in
      latently infected endothelial cells, but not in their mock-infected counterparts.
      In cancer cells, glutamine is often required for glutaminolysis to provide
      intermediates for the tri-carboxylic acid (TCA) cycle and support for the
      production of biosynthetic and bioenergetic precursors. In the absence of
      glutamine, the TCA cycle intermediates alpha-ketoglutarate (alphaKG) and pyruvate
      prevent the death of latently infected cells. Targeted drug inhibition of
      glutaminolysis also induces increased cell death in latently infected cells. KSHV
      infection of endothelial cells induces protein expression of the glutamine
      transporter, SLC1A5. Chemical inhibition of SLC1A5, or knockdown by siRNA, leads
      to similar cell death rates as glutamine deprivation and, similarly, can be
      rescued by alphaKG. KSHV also induces expression of the heterodimeric
      transcription factors c-Myc-Max and related heterodimer MondoA-Mlx. Knockdown of
      MondoA inhibits expression of both Mlx and SLC1A5 and induces a significant
      increase in cell death of only cells latently infected with KSHV, again, fully
      rescued by the supplementation of alphaKG. Therefore, during latent infection of
      endothelial cells, KSHV activates and requires the Myc/MondoA-network to
      upregulate the glutamine transporter, SLC1A5, leading to increased glutamine
      uptake for glutaminolysis. These findings expand our understanding of the
      required metabolic pathways that are activated during latent KSHV infection of
      endothelial cells, and demonstrate a novel role for the extended Myc-regulatory
      network, specifically MondoA, during latent KSHV infection. 

PMID- 26197458
TI  - Substance P Depolarizes Lamprey Spinal Cord Neurons by Inhibiting Background
      Potassium Channels.
AB  - Substance P is endogenously released in the adult lamprey spinal cord and
      accelerates the burst frequency of fictive locomotion. This is achieved by
      multiple effects on interneurons and motoneurons, including an attenuation of
      calcium currents, potentiation of NMDA currents and reduction of the reciprocal
      inhibition. While substance P also depolarizes spinal cord neurons, the
      underlying mechanism has not been resolved. Here we show that effects of
      substance P on background K+ channels are the main source for this
      depolarization. Hyperpolarizing steps induced inward currents during whole-cell
      voltage clamp that were reduced by substance P. These background K+ channels are
      pH sensitive and are selectively blocked by anandamide and AVE1231. These
      blockers counteracted the effect of substance P on these channels and the resting
      membrane potential depolarization in spinal cord neurons. Thus, we have shown now
      that substance P inhibits background K+ channels that in turn induce
      depolarization, which is likely to contribute to the frequency increase observed
      with substance P during fictive locomotion.

PMID- 26197459
TI  - Assessment of bone turnover markers and bone mineral density in normal short
      boys.
AB  - AIM: To investigate whether there is a change in bone turnover-related
      biochemical markers and bone mineral density of children with constitutional
      delay of growth and puberty (CDGP) in the prepubertal period. METHODS: We
      measured serum calcium, phosphorus, alkaline phosphatase, parathormone, 25-OH
      vitamin D, osteocalcin, osteoprotogerin and urinary deoxypyridinoline levels (D
      pyd), and bone mineral density (BMD) in 31 prepubertal boys with CDGP. These
      children were compared with 22 prepubertal boys with familial short stature (FSS)
      and 27 normal prepubertal boys. RESULTS: Urinary D-pyd was significantly high in
      CDGP group as compared to control group (p=0.010). Volumetric BMD did not
      significantly differ between CDGP, FSS, and control groups (p=0.450). Volumetric
      BMD and urinary D-pyd levels of FSS and control groups were similar. Mean or
      median levels of calcium, phosphorus, alkaline phosphatase, parathormone, and
      osteoprotegerin did not significantly differ between CDGP, FSS, and control
      groups. CONCLUSIONS: Our data suggest that prepubertal boys with CDPG have normal
      bone turnover. However, their significantly higher urinary D-pyd levels relative
      to those of FSS and control groups might be an indicator of later development of
      osteoporosis. Therefore, long-term follow-up studies monitoring bone mineral
      status of prepubertal boys with CDPG from prepuberty to adulthood are needed to
      better understand bone metabolism of these patients.

PMID- 26197460
TI  - Treatment of central precocious puberty and early puberty with GnRH analog in
      girls with Williams-Beuren syndrome.
AB  - OBJECTIVE: Little has been published on treatment of precocious puberty in girls
      with Williams-Beuren syndrome (WBS), a condition occurring frequently in this
      group. We analyzed our own data on growth/age at menarche of now adult female
      patients with WBS being diagnosed with central precocious puberty or early
      puberty. Data of patients treated with gonadotropin-releasing hormone (GnRH)
      analog (n=13) were compared with those not treated (control group, n=11).
      PATIENTS: Longitudinal data on the somatic development of 24 now adult female
      patients were analyzed. RESULTS: Medium final height was 157.2+/-6.5 cm compared
      to 151.4+/-5.6 cm in the control group. No significant difference could be found
      in the discrepancy of genetic target height and final height. Prepubertally girls
      were normal weight in both groups; in adulthood the majority of patients were
      overweight/obese. Menarche commenced 11 months after cessation of therapy.
      CONCLUSION: As already known from other studies, hormonal suppression via GnRH
      analog was well tolerated.

PMID- 26197461
TI  - Investigation of androgen receptor gene mutations in a series of 21 patients with
      46,XY disorders of sex development.
AB  - AIM: Androgen receptor (AR) gene mutations are the leading cause of 46,XY
      disorders of sex development (DSD) and are associated with varying degrees of
      androgen insensitivity. The aim of this study is to investigate AR gene mutations
      in 46,XY DSD patients with normal testosterone secretion, either normal or high
      testosterone/dihydrotestosterone (T/DHT) ratio and normal SRD5A2 gene analysis,
      collectively, suggestive of androgen insensitivity syndrome (AIS). METHODS: We
      direct sequenced all eight exons of the AR gene in 21 index patients with varying
      degrees of undervirilization. RESULTS: We detected AR gene alterations in five
      patients. In patients with complete AIS we found p.Val30Met in exon 1 and
      p.Gly689* in exon 4. One patient with partial AIS had p.Gln712Glu in exon 4. In
      two patients with partial phenotype, we found common p.Glu213Glu (c.639G>A) SNP,
      and an additional p.Ile817Ile (c.2451T>C) mutation was found in one of these two
      patients. DISCUSSION: Despite the fact that T/DHT ratio is frequently used in
      diagnosis of AIS, lack of precisely determined cutoffs compromises correct
      diagnosis. Hence, depending on clinical and biochemical findings solely may delay
      correct diagnosis. Direct sequence analysis of the AR is essential for precise
      diagnosis of AIS.

PMID- 26197462
TI  - Adipokines in umbilical cord blood from children born large for gestational age.
AB  - BACKGROUND: The etiology of childhood obesity and the associated morbidity is
      multifactorial. Recently, data suggesting a prenatal programming towards later
      childhood obesity and metabolic deregulation through the intrauterine environment
      has emerged. This study explored the concentrations of adipokines and their
      mutual relationship at birth in children born to non-diabetic mothers. METHODS:
      Adiponectin, leptin and sOB-R were measured using ELISA-based commercial kits in
      umbilical cord blood from 60 neonates (30 born large for gestational age [LGA]
      and 30 born appropriate for gestational age [AGA]). Children exposed to maternal
      diabetes, chronic disease and preeclampsia were excluded. RESULTS: The LGA group
      exhibited significantly elevated concentrations of leptin (p<0.001) and of free
      leptin index (p<0.001) and decreased sOB-R concentrations (p=0.005) when compared
      to the AGA group, which persisted in multiple regression analysis after taking
      the gestational age into account (p=0.048, p<0.001 and p<0.001, respectively).
      Only a trend towards a difference in adiponectin was demonstrated (p=0.057)
      regardless of adjustment (p=0.150). However, the leptin/adiponectin ratio was
      elevated in the LGA group (p=0.008), regardless of adjustment (p=0.039).
      CONCLUSION: The data indicate a disturbance of adipokines in macrosomic newborns
      and that the mutual ratios between adipokines may provide a more sensitive marker
      of metabolic disturbance than any isolated adipokine.

PMID- 26197463
TI  - The effect of intraoperative administration of dexamethasone for PONV prophylaxis
      on perioperative blood glucose level in obese and normal weight children.
AB  - BACKGROUND: The incidence of postoperative nausea and vomiting (PONV) can be
      reduced by dexamethasone. Single-dose administration may cause elevated blood
      glucose levels in obese adults. No data are available for children. OBJECTIVE:
      The aim was to evaluate perioperative blood glucose changes related to body
      weight in children who received dexamethasone. PATIENTS AND METHODS: This
      prospective observational study included 62 children. All patients received total
      intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8
      mg). Blood glucose levels were measured up to 6 h. Standard deviation scores
      (SDS) were calculated using age- and gender-specific body mass index (BMI)
      percentiles, p<0.05. RESULTS: A total of 62 children (11.5+/-2.9 years, median
      SDS 0.43, 29% overweight/obese) were included. Blood glucose levels increased
      from 5.52+/-0.52 to 6.74+/-0.84 mmol/L 6 h after dexamethasone without
      correlation to the BMI-SDS. CONCLUSIONS: This study showed an increase of
      perioperative blood glucose (normoglycemic ranges) after single dose of
      dexamethasone, but no BMI-dependent effect was observed in children. Therefore,
      low-dose dexamethasone may be used in obese children for PONV prophylaxis.

PMID- 26197464
TI  - Current and future perspective of newborn screening: an Indian scenario.
AB  - BACKGROUND: Newborn screening comprises a paramount public health program seeking
      timely detection, diagnosis, and intervention for genetic disorders that may
      otherwise produce serious clinical consequences. Today newborn screening is part
      of the health care system of developed countries, whereas in India, newborn
      screening is still in the toddler stage. METHOD: We searched PubMed with the
      keywords newborn screening for metabolic disorders, newborn screening in India,
      and congenital disorder in neonates, and selected publications that seem
      appropriate. RESULTS: In India, in spite of the high birth rate and high
      frequency of metabolic disorders, newborn screening programs are not part of the
      health care system. At Union Territory, Chandigarh in 2007, newborn screening was
      initiated and is currently ongoing for three disorders, that is, congenital
      hypothyroidism, congenital adrenal hyperplasia, and glucose-6-phosphate
      dehydrogenase (G6PD) deficiency. Prevalence of these disorders is found to be
      1:1400 for congenital hypothyroidism, 1:6334 for congenital adrenal hyperplasia,
      and 1:80 for G6PD deficiency. CONCLUSION: Mandatory newborn screening for
      congenital hypothyroidism should be implemented in India, and other disorders can
      be added in the screening panel on the basis of region-wise prevalence. The
      objective of this review is to provide insight toward present scenario of newborn
      screening in India along with recommendations to combat the hurdles in the
      pathway of mandatory newborn screening.

PMID- 26197465
TI  - Association of physical activity level with depression, anxiety, and quality of
      life in children with type 1 diabetes mellitus.
AB  - BACKGROUND: Children with type 1 diabetes mellitus (T1DM) have low physical
      activity levels and are at high risk for psychosocial morbidities, including
      depression, heightened anxiety and low health-related quality of life (HRQoL).
      OBJECTIVE: The aim of this study was to assess the associations of physical
      activity level with depression, anxiety, and HRQoL in children with T1DM.
      SUBJECTS AND METHODS: A cross-sectional study design, including children with
      T1DM aged between 8 and 12 years and healthy controls, was used. Physical
      activity (PA) level was assessed with the Physical Activity Questionnaire for
      Older Children (PAQ-C). Anxiety was screened by The Screen for Anxiety Related
      Emotional Disorders (SCARED) questionnaire. Depressive symptoms were evaluated
      using the Children's Depression Inventory (CDI). Quality of life was assessed
      with the The Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0). RESULTS: Forty
      seven T1DM and 55 healthy children were included with mean ages of 9.87+/-1.63
      and 9.56+/-1.60 years, respectively. The T1DM group had significantly higher
      depression and anxiety score (p<0.05) and lower HRQoL-child self-report score
      (p<0.05, for all) compared with the control group. Significant associations were
      found between PAQ-C and PedsQL 4.0 (p<0.05), between SCARED and PedsQL 4.0
      (p<0.05), and between HbA1c and PedsQL 4.0 (p<0.05) in children with T1DM.
      CONCLUSIONS: The result of our study suggested that only HRQoL was related to
      physical activity, anxiety and HbA1c in children with T1DM.

PMID- 26197466
TI  - Anaphylaxis to gonadorelin acetate in a girl with central precocious puberty.
AB  - Gonadotropin-releasing hormone analogues are generally regarded as safe drugs.
      Gonadorelin acetate has been widely used for the diagnosis of central precocious
      puberty, and life-threatening reactions to gonadorelin acetate are extremely
      rare. Herein, we described - to the best of our knowledge - the first pediatric
      case in which severe anaphylaxis was encountered after intravenous gonadorelin
      acetate administration. An 8-year-old girl who was diagnosed with central
      precocious puberty was receiving triptorelin acetate treatment uneventfully for 6
      months. In order to evaluate the efficacy of the treatment, an LH-RH stimulation
      test with gonadorelin acetate was planned. Within 3 min after intravenous
      administration of gonadorelin acetate, she lost consciousness and tonic seizures
      began in her hands and feet. She was immediately treated with epinephrine,
      diphenhydramine, and fluids. Her vital signs recovered within 30 min. Based on
      the results, anaphylaxis should be anticipated and the administration of these
      drugs should be performed in a setting that is equipped to deal with systemic
      reactions. 

PMID- 26197467
TI  - Carnitine insufficiency in children with inborn errors of metabolism: prevalence
      and treatment efficacy.
AB  - BACKGROUND: Carnitine is necessary for the transfer of long-chain fatty acids
      from the cytosol into mitochondria for subsequent beta-oxidation. A carnitine
      deficiency results in impaired energy production from fatty acids. METHODS: We
      reviewed the plasma level of total carnitine, free carnitine, and acylcarnitines
      in 1270 children with psychomotor retardation, low growth, and weight parameters.
      Tandem mass spectrometry (MS/MS) was applied. Low free carnitine level in plasma
      was used as a marker of carnitine deficiency. RESULTS: A total of 102 (8%)
      children had free carnitine level <19 MUmol/L (norm 19-60 MUmol/L). As a result
      of the subsequent investigation, hereditary diseases were diagnosed in 76 (3/4)
      children and out of that 19 had very low free carnitine plasma level (<10
      MUmol/L). Fanconi syndrome, fat oxidation defects, primary systemic carnitine
      deficiency, mitochondrial encephalomyopathy, and Noonan syndrome were revealed in
      these 19 children. CONCLUSION: Efficacy of levocarnitine treatment in children
      with very low free carnitine level differs according to pathogenesis of diseases.
      The highest efficacy was observed in primary systemic carnitine deficiency.

PMID- 26197468
TI  - The utility of fractal analysis in clinical neuroscience.
AB  - Physicians and scientists can use fractal analysis as a tool to objectively
      quantify complex patterns found in neuroscience and neurology. Fractal analysis
      has the potential to allow physicians to make predictions about clinical
      outcomes, categorize pathological states, and eventually generate diagnoses. In
      this review, we categorize and analyze the applications of fractal theory in
      neuroscience found in the literature. We discuss how fractals are applied and
      what evidence exists for fractal analysis in neurodegeneration, neoplasm,
      neurodevelopment, neurophysiology, epilepsy, neuropharmacology, and cell
      morphology. The goal of this review is to introduce the medical community to the
      utility of applying fractal theory in clinical neuroscience. 

PMID- 26197469
TI  - Targeted Maximum Likelihood Estimation using Exponential Families.
AB  - Targeted maximum likelihood estimation (TMLE) is a general method for estimating
      parameters in semiparametric and nonparametric models. The key step in any TMLE
      implementation is constructing a sequence of least-favorable parametric models
      for the parameter of interest. This has been done for a variety of parameters
      arising in causal inference problems, by augmenting standard regression models
      with a "clever-covariate." That approach requires deriving such a covariate for
      each new type of problem; for some problems such a covariate does not exist. To
      address these issues, we give a general TMLE implementation based on exponential
      families. This approach does not require deriving a clever-covariate, and it can
      be used to implement TMLE for estimating any smooth parameter in the
      nonparametric model. A computational advantage is that each iteration of TMLE
      involves estimation of a parameter in an exponential family, which is a convex
      optimization problem for which software implementing reliable and computationally
      efficient methods exists. We illustrate the method in three estimation problems,
      involving the mean of an outcome missing at random, the parameter of a median
      regression model, and the causal effect of a continuous exposure, respectively.
      We conduct a simulation study comparing different choices for the parametric
      submodel. We find that the choice of submodel can have an important impact on the
      behavior of the estimator in finite samples. 

PMID- 26197470
TI  - Tumor-Associated Macrophages Provide Significant Prognostic Information in
      Urothelial Bladder Cancer.
AB  - Inflammation is an important feature of carcinogenesis. Tumor-associated
      macrophages (TAMs) can be associated with either poor or improved prognosis,
      depending on their properties and polarization. Current knowledge of the
      prognostic significance of TAMs in bladder cancer is limited and was investigated
      in this study. We analyzed 184 urothelial bladder cancer patients undergoing
      transurethral resection of a bladder tumor or radical cystectomy. CD68 (pan
      macrophage marker), MAC387 (polarized towards type 1 macrophages), and CLEVER
      1/Stabilin-1 (type 2 macrophages and lymphatic/blood vessels) were detected
      immunohistochemically. The median follow-up time was 6.0 years. High macrophage
      counts associated with a higher pT category and grade. Among patients undergoing
      transurethral resection, all studied markers apart from CLEVER-1/Stabilin-1 were
      associated with increased risk of progression and poorer disease-specific and
      overall survival in univariate analyses. High levels of two macrophage markers
      (CD68/MAC387+/+ or CD68/CLEVER-1+/+ groups) had an independent prognostic role
      after transurethral resection in multivariate analyses. In the cystectomy cohort,
      MAC387, alone and in combination with CD68, was associated with poorer survival
      in univariate analyses, but none of the markers were independent predictors of
      outcome in multivariate analyses. In conclusion, this study demonstrates that
      macrophage phenotypes provide significant independent prognostic information,
      particularly in bladder cancers undergoing transurethral resection.

PMID- 26197472
TI  - The Relationship between Depression and Asthma: A Meta-Analysis of Prospective
      Studies.
AB  - BACKGROUND: Previous studies have suggested that asthmatic patients often have
      comorbid depression; however, temporal associations remain unclear. OBJECTIVES:
      To determine whether depression predicts asthma and, conversely, whether asthma
      predicts depression. METHODS: A literature search was conducted without language
      restrictions using Pubmed, Embase, Cochrane and PsycINFO for studies published
      before January, 2015. Papers referenced by the obtained articles were also
      reviewed. Only comparative prospective studies with reported risk estimates of
      the association between depression and asthma were included. In order to
      investigate whether one of these conditions was predictive of the other, studies
      were excluded if enrolled participants had pre-existing depression or asthma. A
      random-effects model was used to calculate the pooled risk estimates for two
      outcomes: depression predicting asthma and asthma predicting depression. RESULTS:
      Seven citations, derived from 8 cohort studies, met our inclusion criteria. Of
      these, six studies reported that depression predicted incident adult-onset
      asthma, including 83684 participants and 2334 incident cases followed for 8 to 20
      years. Conversely, two studies reported that asthma predicted incident
      depression. These studies involved 25566 participants and 2655 incident cases
      followed for 10 and 20 years, respectively. The pooled adjusted relative risks
      (RRs) of acquiring asthma associated with baseline depression was 1.43 (95% CI,
      1.28-1.61) (P<0.001). The adjusted RRs for acquiring depression associated with
      baseline asthma was 1.23 (95% CI, 0.72-2.10) (P = 0.45). CONCLUSIONS: Depression
      was associated with a 43% increased risk of developing adult-onset asthma.
      However, asthma did not increase the risk of depression based on limited studies.
      Further prospective studies ascertaining the true association between asthma and
      subsequent risk of depression are warranted.

PMID- 26197471
TI  - Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation in Intermediate
      Risk Acute Myeloid Leukemia Adult Patients in First Complete Remission: A Meta
      Analysis of Prospective Studies.
AB  - Hematopoietic stem cell transplantation (HSCT) and consolidation chemotherapy
      have been used to treat intermediate-risk acute myeloid leukemia (AML) patients
      in first complete remission (CR1). However, it is still unclear which treatments
      are most effective for these patients. The aim of our study was to analyze the
      relapse-free survival (RFS) and overall survival (OS) benefit of allogeneic HSCT
      (alloHSCT) for intermediate-risk AML patients in CR1. A meta-analysis of
      prospective trials comparing alloHSCT to non-alloHSCT (autologous HSCT [autoHSCT]
      and/or chemotherapy) was undertaken. We systematically searched PubMed, Embase,
      and the Cochrane Library though October 2014, using keywords and relative MeSH or
      Emtree terms, 'allogeneic'; 'acut*' and 'leukem*/aml/leukaem*/leucem*/leucaem*';
      and 'nonlympho*' or 'myelo*'. A total of 7053 articles were accessed. The primary
      outcomes were RFS and OS, while the secondary outcomes were treatment-related
      mortality (TRM) and relapse rate (RR). Hazard ratios (HR) and 95% confidence
      intervals (CI) were calculated for each outcome. The primary outcomes were RFS
      and OS, while the secondary outcomes were TRM and RR. We included 9 prospective
      controlled studies including 1950 adult patients. Patients with intermediate-risk
      AML in CR1 who received either alloHSCT or non-alloHSCT were considered eligible.
      AlloHSCT was found to be associated with significantly better RFS, OS, and RR
      than non-alloHSCT (HR, 0.684 [95% CI: 0.48, 0.95]; HR, 0.76 [95% CI: 0.61, 0.95];
      and HR, 0.58 [95% CI: 0.45, 0.75], respectively). TRM was significantly higher
      following alloHSCT than non-alloHSCT (HR, 3.09 [95% CI: 1.38, 6.92]). However,
      subgroup analysis showed no OS benefit for alloHSCT over autoHSCT (HR, 0.99 [95%
      CI: 0.70, 1.39]). In conclusion, alloHSCT is associated with more favorable RFS,
      OS, and RR benefits (but not TRM outcomes) than non-alloHSCT generally, but does
      not have an OS advantage over autoHSCT specifically, in patients with
      intermediate-risk AML in CR1.

PMID- 26197473
TI  - Habitat Heterogeneity Affects Plant and Arthropod Species Diversity and Turnover
      in Traditional Cornfields.
AB  - The expansion of the agricultural frontier by the clearing of remnant forests has
      led to human-dominated landscape mosaics. Previous studies have evaluated the
      effect of these landscape mosaics on arthropod diversity at local spatial scales
      in temperate and tropical regions, but little is known about fragmentation
      effects in crop systems, such as the complex tropical traditional crop systems
      that maintain a high diversity of weeds and arthropods in low-Andean regions. To
      understand the factors that influence patterns of diversity in human-dominated
      landscapes, we investigate the effect of land use types on plant and arthropod
      diversity in traditionally managed cornfields, via surveys of plants and
      arthropods in twelve traditional cornfields in the Colombian Andes. We estimated
      alpha and beta diversity to analyze changes in diversity related to land uses
      within a radius of 100 m to 1 km around each cornfield. We observed that forests
      influenced alpha diversity of plants, but not of arthropods. Agricultural lands
      had a positive relationship with plants and herbivores, but a negative
      relationship with predators. Pastures positively influenced the diversity of
      plants and arthropods. In addition, forest cover seemed to influence changes in
      plant species composition and species turnover of herbivore communities among
      cornfields. The dominant plant species varied among fields, resulting in high
      differentiation of plant communities. Predator communities also exhibited high
      turnover among cornfields, but differences in composition arose mainly among rare
      species. The crop system evaluated in this study represents a widespread
      situation in the tropics, therefore, our results can be of broad significance.
      Our findings suggest that traditional agriculture may not homogenize biological
      communities, but instead could maintain the regional pool of species through high
      beta diversity. 

PMID- 26197474
TI  - Can Twitter Be a Source of Information on Allergy? Correlation of Pollen Counts
      with Tweets Reporting Symptoms of Allergic Rhinoconjunctivitis and Names of
      Antihistamine Drugs.
AB  - Pollen forecasts are in use everywhere to inform therapeutic decisions for
      patients with allergic rhinoconjunctivitis (ARC). We exploited data derived from
      Twitter in order to identify tweets reporting a combination of symptoms
      consistent with a case definition of ARC and those reporting the name of an
      antihistamine drug. In order to increase the sensitivity of the system, we
      applied an algorithm aimed at automatically identifying jargon expressions
      related to medical terms. We compared weekly Twitter trends with National Allergy
      Bureau weekly pollen counts derived from US stations, and found a high
      correlation of the sum of the total pollen counts from each stations with tweets
      reporting ARC symptoms (Pearson's correlation coefficient: 0.95) and with tweets
      reporting antihistamine drug names (Pearson's correlation coefficient: 0.93).
      Longitude and latitude of the pollen stations affected the strength of the
      correlation. Twitter and other social networks may play a role in allergic
      disease surveillance and in signaling drug consumptions trends.

PMID- 26197475
TI  - Search Engine for Antimicrobial Resistance: A Cloud Compatible Pipeline and Web
      Interface for Rapidly Detecting Antimicrobial Resistance Genes Directly from
      Sequence Data.
AB  - BACKGROUND: Antimicrobial resistance remains a growing and significant concern in
      human and veterinary medicine. Current laboratory methods for the detection and
      surveillance of antimicrobial resistant bacteria are limited in their
      effectiveness and scope. With the rapidly developing field of whole genome
      sequencing beginning to be utilised in clinical practice, the ability to
      interrogate sequencing data quickly and easily for the presence of antimicrobial
      resistance genes will become increasingly important and useful for informing
      clinical decisions. Additionally, use of such tools will provide insight into the
      dynamics of antimicrobial resistance genes in metagenomic samples such as those
      used in environmental monitoring. RESULTS: Here we present the Search Engine for
      Antimicrobial Resistance (SEAR), a pipeline and web interface for detection of
      horizontally acquired antimicrobial resistance genes in raw sequencing data. The
      pipeline provides gene information, abundance estimation and the reconstructed
      sequence of antimicrobial resistance genes; it also provides web links to
      additional information on each gene. The pipeline utilises clustering and read
      mapping to annotate full-length genes relative to a user-defined database. It
      also uses local alignment of annotated genes to a range of online databases to
      provide additional information. We demonstrate SEAR's application in the
      detection and abundance estimation of antimicrobial resistance genes in two novel
      environmental metagenomes, 32 human faecal microbiome datasets and 126 clinical
      isolates of Shigella sonnei. CONCLUSIONS: We have developed a pipeline that
      contributes to the improved capacity for antimicrobial resistance detection
      afforded by next generation sequencing technologies, allowing for rapid detection
      of antimicrobial resistance genes directly from sequencing data. SEAR uses raw
      sequencing data via an intuitive interface so can be run rapidly without
      requiring advanced bioinformatic skills or resources. Finally, we show that SEAR
      is effective in detecting antimicrobial resistance genes in metagenomic and
      isolate sequencing data from both environmental metagenomes and sequencing data
      from clinical isolates.

PMID- 26197477
TI  - Maternal prenatal and/or postnatal n-3 long chain polyunsaturated fatty acids
      (LCPUFA) supplementation for preventing allergies in early childhood.
AB  - BACKGROUND: Allergies have become more prevalent globally over the last 20 years.
      Dietary consumption of n-3 (or omega 3) long chain polyunsaturated fatty acids
      (LCPUFA) has declined over the same period of time. This, together with the known
      role of n-3 LCPUFA in inhibiting inflammation, has resulted in speculation that n
      3 LCPUFA may prevent allergy development. Dietary n-3 fatty acids supplements may
      change the developing immune system of the newborn before allergic responses are
      established, particularly for those with a genetic predisposition to the
      production of the immunoglobulin E (IgE) antibody. Individuals with IgE-mediated
      allergies have both the signs and symptoms of the allergic disease and a positive
      skin prick test (SPT) to the allergen. OBJECTIVES: To assess the effect of n-3
      LCPUFA supplementation in pregnant and/or breastfeeding women on allergy outcomes
      (food allergy, atopic dermatitis (eczema), allergic rhinitis (hay fever) and
      asthma/wheeze) in their children. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (6 August 2014), PubMed (1966 to
      01 August 2014), CINAHL via EBSCOhost (1984 to 01 August 2014), Scopus (1995 to
      01 August 2014), Web of Knowledge (1864 to 01 August 2014) and ClinicalTrials.gov
      (01 August 2014) and reference lists of retrieved studies. SELECTION CRITERIA: We
      included randomised controlled trials (RCTs) evaluating the effect of n-3 LCPUFA
      supplementation of pregnant and/or lactating women (compared with placebo or no
      treatment) on allergy outcomes of the infants or children. Trials using a cross
      over design and trials examining biochemical outcomes only were not eligible for
      inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed eligibility and trial quality and performed data extraction. Where the
      review authors were also investigators on trials selected, an independent
      reviewer assessed trial quality and performed data extraction. MAIN RESULTS:
      Eight trials involving 3366 women and their 3175 children were included in the
      review. In these trials, women were supplemented with n-3 LCPUFA during pregnancy
      (five trials), lactation (two trials) or both pregnancy and lactation (one
      trial). All trials randomly allocated women to either a n-3 LCPUFA supplement or
      a control group. The risk of bias varied across the eight included trials in this
      review with only two trials with a low risk of selection, performance and
      attrition bias.N-3 LCPUFA supplementation showed a clear reduction in the primary
      outcome of any allergy (medically diagnosed IgE mediated) in children aged 12 to
      36 months (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.98; two
      RCTs; 823 children), but not beyond 36 months (RR 0.86, 95% CI 0.61 to 1.20; one
      RCT, 706 children). For any allergy (medically diagnosed IgE mediated and/or
      parental report), no clear differences were seen in children either at 12 to 36
      months (RR 0.89, 95% CI 0.71 to 1.11; two RCTs, 823 children) or beyond 36 months
      of age (RR 0.96, 95% CI 0.84 to 1.09; three RCTs, 1765 children).For the
      secondary outcomes of specific allergies there were no clear differences for food
      allergies at 12 to 36 months and beyond 36 months, but a clear reduction was seen
      for children in their first 12 months with n-3 LCPUFA (both for medically
      diagnosed IgE mediated and medically diagnosed IgE mediated and/or parental
      report). There was a clear reduction in medically diagnosed IgE-mediated eczema
      with n-3 LCPUFA for children 12 to 36 months of age, but not at any other time
      point for both medically diagnosed IgE mediated and medically diagnosed IgE
      mediated and/or parental report. No clear differences for allergic rhinitis or
      asthma/wheeze were seen at any time point for both medically diagnosed IgE
      mediated, and medically diagnosed IgE mediated and/or parental report.There was a
      clear reduction in children's sensitisation to egg and sensitisation to any
      allergen between 12 to 36 months of age when mothers were supplemented with n-3
      LCPUFA.In terms of safety for the mother and child, n-3 LCPUFA supplementation
      during pregnancy did not show increased risk of postpartum haemorrhage or early
      childhood infections. AUTHORS' CONCLUSIONS: Overall, there is limited evidence to
      support maternal n-3 LCPUFA supplementation during pregnancy and/or lactation for
      reducing allergic disease in children. Few differences in childhood allergic
      disease were seen between women who were supplemented with n-3 LCPUFA and those
      who were not.

PMID- 26197479
TI  - Correction: Hepatitis C Virus Nonstructural Protein 5A Inhibits MG132-Induced
      Apoptosis of Hepatocytes in Line with NF-kappaB-Nuclear Translocation.

PMID- 26197476
TI  - Association of Anti-GT1a Antibodies with an Outbreak of Guillain-Barre Syndrome
      and Analysis of Ganglioside Mimicry in an Associated Campylobacter jejuni Strain.
AB  - An outbreak of Guillain-Barre syndrome (GBS), subsequent to Campylobacter jejuni
      enteritis, occurred in China in 2007. Serum anti-ganglioside antibodies were
      measured in GBS patients and controls. Genome sequencing was used to determine
      the phylogenetic relationship among three C. jejuni strains from a patient with
      GBS (ICDCCJ07001), a patient with gastroenteritis (ICDCCJ07002) and a healthy
      carrier (ICDCCJ07004), which were all associated with the outbreak. The
      ganglioside-like structures of the lipo-oligosaccharides of these strains were
      determined by mass spectrometry. Seventeen (53%) of the GBS patients had anti
      GT1a IgG antibodies. GT1a mimicry was found in the lipo-oligosaccharides of
      strain ICDCCJ07002 and ICDCCJ07004; but a combination of GM3/GD3 mimics was
      observed in ICDCCJ07001, although this patient had anti-GT1a IgG antibodies. A
      single-base deletion in a glycosyltransferase gene caused the absence of GT1a
      mimicry in ICDCCJ07001. The phylogenetic tree showed that ICDCCJ07002 and
      ICDCCJ07004 were genetically closer to each other than to ICDCCJ07001. C. jejuni,
      bearing a GT1a-like lipo-oligosaccharide, might have caused the GBS outbreak and
      the loss of GT1a mimicry may have helped ICDCCJ07001 to survive in the host. 

PMID- 26197478
TI  - Transglycosylation Activity of Glycosynthase Mutants of Endo-beta-N
      Acetylglucosaminidase from Coprinopsis cinerea.
AB  - Endo-beta-N-acetylglucosaminidase (ENGase), which catalyzes hydrolysis of N
      linked oligosaccharides, is a useful tool for analyzing oligosaccharide contents
      of glycoproteins. However, there are only a few known ENGases that can catalyze
      the hydrolysis of human complex type oligosaccharides, and although commercially
      available, they are expensive. Here, we report the cloning of two ENGase encoding
      cDNAs from the basidiomycete fungus Coprinopsis cinerea, Endo-CC1 and Endo-CC2.
      We successfully expressed recombinant His6-tagged Endo-CC1 and Endo-CC2 in
      Escherichia coli and purified them for enzymatic characterization. Both Endo-CC1
      and Endo-CC2 showed hydrolytic activity on high-mannose and complex type
      oligosaccharides. Since Endo-CC1 could be prepared more easily than Endo-CC2 from
      E. coli cultures, we examined the enzymatic properties of Endo-CC1 in detail. Our
      results showed that Endo-CC1 acted on both N-linked high-mannose type and
      sialobiantennary type complex oligosaccharides of glycoproteins RNase B and human
      transferrin, respectively, but not on the sialotriantennary type complex
      oligosaccharide of glycoprotein fetuin. Examination of the transglycosylation
      activity of Endo-CC1 revealed that the wild-type Endo-CC1 could not transfer the
      sialobiantennary type complex oligosaccharide onto the deglycosylated RNase B. To
      obtain an Endo-CC1 mutant with desired transglycosylation activity, we performed
      mutation analysis of the active site residue Asn 180 (N180), known to be
      important for catalysis, by individually replacing it with the remaining 19 amino
      acid residues. Transglycosylation analyses of these mutants led us to identify
      one mutant, namely Endo-CC1N180H, which exhibited the desired transglycosylation
      activity. Taken together, we suggest that Endo-CC1 would potentially be a
      valuable tool for analyzing oligosaccharides on glycoproteins, as large
      quantities of it could be made available more easily and less expensively than
      the currently used enzyme, Endo-M.

PMID- 26197480
TI  - Comparison of Body Composition Assessed by Dual-Energy X-Ray Absorptiometry and
      BMI in Current and Former U.S. Navy Service Members.
AB  - BACKGROUND: Little is known of the diagnostic accuracy of BMI in classifying
      obesity in active duty military personnel and those that previously served. Thus,
      the primary objectives were to determine the relationship between lean and fat
      mass, and body fat percentage (BF%) with BMI, and assess the agreement between
      BMI and BF% in defining obesity. METHODS: Body composition was measured by dual
      energy X-ray absorptiometry in 462 males (20-91 years old) who currently or
      previously served in the U.S. Navy. A BMI of >= 30 kg/m2 and a BF% >= 25% were
      used for obesity classification. RESULTS: The mean BMI (+/- SD) and BF% were 28.8
      +/- 4.1 and 28.9 +/- 6.6%, respectively, with BF% increasing with age. Lean mass,
      fat mass, and BF% were significantly correlated with BMI for all age groups. The
      exact agreement of obesity defined by BMI and BF% was fair (61%), however, 38%
      were misclassified by a BMI cut-off of 30 when obesity was defined by BF%.
      CONCLUSIONS: From this data we determined that there is a good correlation
      between body composition and BMI, and fair agreement between BMI and BF% in
      classifying obesity in a group of current and former U.S. Navy service members.
      However, as observed in the general population, a significant proportion of
      individuals with excess fat are misclassified by BMI cutoffs.

PMID- 26197482
TI  - Do Earthquakes Shake Stock Markets?
AB  - This paper examines how major earthquakes affected the returns and volatility of
      aggregate stock market indices in thirty-five financial markets over the last
      twenty years. Results show that global financial markets are resilient to shocks
      caused by earthquakes even if these are domestic. Our analysis reveals that, in a
      few instances, some macroeconomic variables and earthquake characteristics (gross
      domestic product per capita, trade openness, bilateral trade flows, earthquake
      magnitude, a tsunami indicator, distance to the epicenter, and number of
      fatalities) mediate the impact of earthquakes on stock market returns, resulting
      in a zero net effect. However, the influence of these variables is market
      specific, indicating no systematic pattern across global capital markets. Results
      also demonstrate that stock market volatility is unaffected by earthquakes,
      except for Japan.

PMID- 26197481
TI  - Development of a Transgenic Mouse with R124H Human TGFBI Mutation Associated with
      Granular Corneal Dystrophy Type 2.
AB  - PURPOSE: To investigate the phenotype and predisposing factors of a granular
      corneal dystrophy type 2 transgenic mouse model. METHODS: Human TGFBI cDNA with
      R124H mutation was used to make a transgenic mouse expressing human protein
      (TGFBIR124H mouse). Reverse transcription PCR (RT-PCR) was performed to analyze
      TGFBIR124H expression. A total of 226 mice including 23 homozygotes, 106
      heterozygotes and 97 wild-type mice were examined for phenotype. Affected mice
      were also examined by histology, immunohistochemistry and electron microcopy.
      RESULTS: RT-PCR confirmed the expression of TGFBIR124H in transgenic mice.
      Corneal opacity defined as granular and lattice deposits was observed in 45.0% of
      homozygotes, 19.4% of heterozygotes. The incidence of corneal opacity was
      significantly higher in homozygotes than in heterozygotes (p = 0.02). Histology
      of affected mice was similar to histology of human disease. Lesions were Congo
      red and Masson Trichrome positive, and were observed as a deposit of amorphous
      material by electron microscopy. Subepithelial stroma was also stained with
      thioflavin T and LC3, a marker of autophagy activation. The incidence of corneal
      opacity was higher in aged mice in each group. Homozygotes were not necessarily
      more severe than heterozygotes, which deffers from human cases. CONCLUSIONS: We
      established a granular corneal dystrophy type 2 mouse model caused by R124H
      mutation of human TGFBI. Although the phenotype of this mouse model is not
      equivalent to that in humans, further studies using this model may help elucidate
      the pathophysiology of this disease.

PMID- 26197483
TI  - Is tibetan polyandry adaptive? : Methodological and metatheoretical analyses.
AB  - This paper addresses methodological and metatheoretical aspects of the ongoing
      debate over the adaptive significance of Tibetan polyandry. Methodological
      contributions include a means of estimating relatedness of fraternal co-husbands
      given multigenerational polyandry, and use of Hamilton's rule and a member-joiner
      model to specify how inclusive fitness gains of co-husbands may vary according to
      seniority, opportunity costs, and group size. These methods are applied to
      various data sets, particularly that of Crook and Crook (1988). The
      metatheoretical discussion pivots on the critique by evolutionary psychologists
      of adaptationist accounts of polyandry. Contrary to this critique, I argue that
      valid adaptationist explanations of such practices do not necessitate cognitive
      mechanisms evolved specifically to produce polyandry, nor that there must have
      been exact equivalents of Tibetan agricultural estates and social institutions in
      human evolutionary history. Specific issues raised when one posits either kin
      selection or cultural evolution to explain the adaptive features of Tibetan
      polyandry are also discussed. 

PMID- 26197484
TI  - The nubility hypothesis : The human breast as an honest signal of residual
      reproductive value.
AB  - A new hypothesis is proposed to explain the perennially enlarged breasts of human
      females. The nubility hypothesis proposes that hominid females evolved protruding
      breasts because the size and shape of breasts function as an honest signal of
      residual reproductive value. Hominid females with greater residual reproductive
      value were preferred by males once reliable cues to ovulation were lost and long
      term bonding evolved. This adaptation was favored because female-female
      competition for investing males increased once hominid males began to provide
      valuable resources. 

PMID- 26197485
TI  - Literary study and evolutionary theory : A review essay.
AB  - Several recent books have claimed to integrate literary study with evolutionary
      biology. All of the books here considered, except Robert Storey's, adopt
      conceptions of evolutionary theory that are in some way marginal to the Darwinian
      adaptationist program. All the works attempt to connect evolutionary study with
      various other disciplines or methodologies: for example, with cultural
      anthropology, cognitive psychology, the psychology of emotion, neurobiology,
      chaos theory, or structuralist linguistics. No empirical paradigm has yet been
      established for this field, but important steps have been taken, especially by
      Storey, in formulating basic principles, identifying appropriate disciplinary
      connections, and marking out lines of inquiry. Reciprocal efforts are needed from
      biologists and social scientists. 

PMID- 26197486
TI  - The sociobiology of everyday life : A new look at a very old novel.
AB  - The 1000-year-old novel The Tale of Genji, written by Murasaki Shikibu around
      1002 CE, shows the operation of general principles of sociobiology. Isolated from
      western influences and cloaked in Japanese traditions, the common traits
      associated with reproductive processes are clearly evident. The novel depicts the
      differential investment of males and females in offspring, male competitive
      behaviors, and concerns for paternity, kin selection, reciprocal social exchange,
      species-typical emotional expression, female mate choice, positive assortative
      mating, and acknowledgment of hereditary transmission of physical and
      psychological traits. The nature of human behavior in Genji's time seems little
      different than now and has all the attributes of species-specific and universal
      traits. Indeed, it can be argued that the fundamental characteristics of Homo
      sapiens have never changed, being influenced only in form by culture. The
      qualitative and quantitative evaluation of ancient texts is a strong methodology
      for understanding the invariant nature of human behavior. 

PMID- 26197487
TI  - Intergenerational context discontinuity affects the onset of puberty : A
      comparison of parent-child dyads in West and East Germany.
AB  - The assumption that the onset of puberty is a context-sensitive marker of a
      reproductive strategy is tested by comparing parental and filial childhood
      context and somatic development in West and East Germany. Sixty-eight mother
      daughter dyads and 35 father-son dyads were taken from two samples of families
      from Osnabruck in West Germany and Halle in East Germany. According to the
      observed context discontinuity between the generations in the male dyads, linear
      regression models show that no indicator of male sexual maturation was influenced
      significantly by the somatic development of the father. Instead of an inherited
      timing of maturation, antecedent distal factors like socioeconomic childhood
      context variables and critical life events lead to an acceleration of male sexual
      maturation. Finally we test the effect of two different conditions of childhood
      context continuity on daughter's age at menarche with maternal age at menarche
      controlled. Linear regression models show that mother's age at menarche predicts
      daughter's age at menarche only under the condition of contextual continuity
      between generations, which was the case in the West German sample only. In East
      Germany, where mother's age at menarche had no significant effect, the amount of
      variance explained by childhood context variables was almost the same. These
      results indicate the context sensitivity of somatic development which seems to
      follow an evolutionary rationale. 

PMID- 26197489
TI  - Competition for Pollination and   the Evolution of Flowering Time.

PMID- 26197490
TI  - Chemical and Genetic Diversity of Ligularia hodgsonii in China.
AB  - Ligularia hodgsonii was found to be diverse in China. Furanoeremophilanes were
      isolated from samples collected in Yunnan Province, while such compounds were
      absent from samples from Sichuan, Gansu, and Chongqing. DNA sequencing showed
      that the Yunnan samples were also genetically distinct. gamma-Humulene and a new
      bisabolane sesquiterpene were isolated.

PMID- 26197488
TI  - Joint Stiffness Is Heritable and Associated with Fibrotic Conditions and Joint
      Replacement.
AB  - OBJECTIVE: Joint stiffness is a common, debilitating, age-related symptom, which
      may be seen after total joint replacement (TJR). Stiffness also occurs in
      fibrotic conditions such as shoulder capsulitis and Dupuytren's contracture. We
      speculated that the two traits (TJR and fibrotic disease) are linked
      pathogenically. METHODS: Using the TwinsUK NIHR BRC BioResource we tested the
      hypotheses that 1) joint (hip and knee) stiffness, TJR (hip and knee), and
      fibrotic conditions are associated and 2) genetic factors contribute to them.
      RESULTS: Participating twins (n = 9718) had completed self-reported
      questionnaires on the traits of interest. All three traits were significantly
      associated with increasing age and body mass index (BMI), as well as female sex,
      on univariate analysis. Multivariable logistic regression analyses showed a
      significant association between TJR and joint stiffness (OR = 3.96, 95%
      confidence interval, CI 2.77-5.68) and between fibrotic conditions and joint
      stiffness (OR = 2.39, 1.74-3.29), adjusting for age, sex, BMI and twin
      relatedness. Monozygotic versus dizygotic intraclass correlations gave
      heritability estimates for TJR = 46% and joint stiffness = 32%. CONCLUSION: That
      fibrotic conditions, joint stiffness and TJR are significantly associated
      suggests a common disease process, possibly fibrosis, which is genetically
      mediated.

PMID- 26197491
TI  - Constituents of Ligularia brassicoides Collected in China: A New Diels-Alder
      Adduct of Eremophilan-10beta-ol and Methacrylic Acid.
AB  - Chemical study of four samples of Ligularia brassicoides collected in Sichuan
      Province of China afforded 18 compounds, five of which were new. LC-MS profiles
      were somehow similar to each other, although the compound ratio was slightly
      different. One of the new compound was a Diels-Alder adduct between
      franoeremophilan-10beta-ol and methacrylic acid.

PMID- 26197492
TI  - Four New Sesquiterpenoids from Ligularia subspicata Collected in China; Isolation
      of a Bakkane-type Lactone, an Eremophilane-type Lactone, and Two Ortho Esters.
AB  - A bakkane type lactone, an eremophilane type lactone, and two ortho esters were
      isolated from Ligularia subspicata collected in Sichuan Province, China. The
      ortho ester type compound has been isolated from Ligularia for the first time.

PMID- 26197493
TI  - Natural Caryophyllane Sesquiterpenoids from Rumphella antipathies.
AB  - Two new natural caryophyllane-type sesquiterpenoids, 1 and 2, were isolated from
      the gorgonian coral Rumphella antipathies. Standard spectroscopic techniques were
      used to determine the structures of caryophyllanes 1 and 2.

PMID- 26197494
TI  - Bioactive Compounds in Wild, In vitro Obtained, Ex vitro Adapted, and Acclimated
      Plants of Centaurea davidovii (Asteraceae).
AB  - In vitro cultures were initiated from a single seed of Centaurea davidovii. Whole
      plantlets were regenerated and cultivated for several months on agar-solidified
      nutrient media differing by their composition: basal MS medium, MS medium
      supplemented with plant growth regulators, and liquid MS medium. Plantlets were
      ex vitro adapted and successfully acclimated to open-air conditions; flowering
      was observed in some individuals in the first summer, and mass flowering during
      the second summer. The contents of the total flavonoids and the total phenolic
      compounds were determined spectrophotometrically in the leaves of the in vitro
      plantlets cultured on different media, and then compared with those in the leaves
      of the wild plants and in the leaves of the acclimated plants of the field plot.
      The sesquiterpene lactone 8alpha-(5'-hydroxyangeloyl)-salonitenolide was
      determined by HPLC in leaf samples of C. davidovii wild plants, in vitro obtained
      plantlets and ex vitro acclimated plants in the greenhouse and on the
      experimental field plot. The composition of the nutrient medium influenced the
      contents of all studied bioactive substances. The highest concentrations of all
      tested secondary metabolites were detected in the leaves of the acclimated plants
      during mass flowering, the content of the lactone reaching 56.2 mg/g DW, which
      was several times more than in the other leaf samples. The obtained results
      revealed both the effectiveness of biotechnological methods for propagation and
      conservation of rare and endangered plant species, and the possibility to use C.
      davidovii plants ex vitro acclimated to field conditions as a source of secondary
      metabolites with potential biological activity.

PMID- 26197495
TI  - New Laurene-type Sesquiterpene from Bornean Laurencia nangii.
AB  - We report the chemical composition of a population of Bornean Laurencia nangii
      Masuda. A new compound, neolaurene (1), along with five known metabolites,
      neolaurallene (2), 2,10-dibromo-3-chloro-alpha-chamigrene (3), deoxyprepacifenol
      (4), cycloelatanene B (5) and intricatetraol (6), were isolated and their
      chemical structures elucidated based on spectroscopic data. In addition, their
      cytotoxicity and antibacterial activity were evaluated.

PMID- 26197496
TI  - New Furanone and Sesquiterpene from the Pericarp of Calocedrus formosana.
AB  - One new gamma-lactone, namely calolactone (1), together with one new drimane-type
      sesquiterpene, namely caloterpene (2), were isolated from the pericarp of
      Calocedrus formosana Florin. Their structures were elucidated by spectroscopic
      and mass spectrometric analysis.

PMID- 26197497
TI  - The Importance of the 5-Alkyl Substituent for the Violet Smell of Ionones:
      Synthesis of Racemic 5-Demethyl-alpha-ionone.
AB  - The synthesis and the odor tonalities of racemic 5-demethyl-alpha-ionone are
      described. This synthetic ionone derivative did not show the typical floral-woody
      violet smell of alpha-ionone, definitely proving the importance of a suitably
      sized and spatially oriented alkyl substituent at C(5) for stimulating olfactory
      receptors of ionones.

PMID- 26197498
TI  - Antiproliferative Activity of seco-Oxacassanes from Acacia schaffneri.
AB  - This work reports the antiproliferative activity of seco-oxacassanes 1-3,
      isolated from Acacia schaffneri, against human colon (HT-29), lung (A-549), and
      melanoma (UACC-62) cancer cell lines, as well as against their non-malignant
      counterparts CCD-841 CoN, MRC-5, and VH-10, respectively, using the
      sulforhodamine B test. While compounds 1 and 3 were inactive, 2 presented strong
      activity with IC50 values between 0.12 and 0.92 MUg mL(-1). The cytotoxicity
      mechanisms of 2 were investigated by cell cycle analysis and through DNA repair
      pathways, indicating that the compound is capable of arresting the cell cycle in
      the G0/G1 phase. This effect might be generated through damage to DNA by
      alkylation. In addition, compound 2 was able to decrease HT-29 migration.

PMID- 26197499
TI  - neo-Clerodane Diterpenoids from Ajuga macrosperma var. breviflora.
AB  - Six new naturally occurring ajugarin-like neo-clerodane diterpenoids,
      ajugaflorins A-F, along with six known compounds [the parent ajugarin I,
      ajugalides B and C, ajugamarin F4, ajugamacrin E, and ajugatakasin B] were
      isolated from A. macrosperma var. breviflora. The structures were elucidated by
      extensive NMR spectroscopic and MS analyses and comparison with data previously
      reported.

PMID- 26197500
TI  - Three New C20-Diterpenoid Alkaloids from Aconitum tanguticum var. trichocarpum.
AB  - Continuous investigations on the whole herbs of Aconitum tanguticum var.
      trichocarpum led to the isolation of three new C20-diterpenoid alkaloids
      trichocarpisines A-C (1-3). Their structures were elucidated on the basis of
      extensive interpretation of the spectroscopic data.

PMID- 26197501
TI  - Manoalide-related Sesterterpene from the Marine Sponge Luffariella variabilis.
AB  - A new manoalide-related sesterterpene, (4E,6E)-dehydro-25-O-methylmanoalide (1),
      was isolated from the organic extracts of the Bornean marine sponge Luffariella
      variabilis, together with the known compound (4E,6E)-dehydromanoalide (2). The
      structure of compound 1 was elucidated by interpretation of its spectroscopic
      data.

PMID- 26197502
TI  - Oxygenated Terpenes from Indo-Pacific Nudibranchs: Scalarane Sesterterpenes from
      Glossodoris hikuerensis and 12-Acetoxy Dendrillolide A from Goniobranchus
      albonares.
AB  - Two new scalarane sesterterpenes (1, 2) were characterized from an organic
      extract of a single specimen of the nudibranch Glossodoris hikuerensis collected
      from Bali. 12-Acetoxy dendrillolide A (10) was identified from specimens of
      Goniobranchus albonares, while dendrillolide A (11) was isolated both from G.
      albonares and its sponge diet. The structures and relative configuration of the
      new metabolites have been elucidated by analysis of their spectroscopic data.

PMID- 26197503
TI  - Germinating Seeds of Citrus aurantium a Good Source of Bioactive Limonoids.
AB  - A simple method to obtain extracts enriched in bioactive limonoids from Citrus
      aurantium L. seeds has been developed, using solvents of increasing polarity. 1H
      NMR data from the extracts revealed that the highest amounts of limonoids were
      present in the t-butylmethylether extract. The comparison between extracts
      obtained from dormant and germinating seeds showed that the latter contained
      almost double amounts of limonoids, revealing germinating seeds as an excellent
      source of those bioactive compounds.

PMID- 26197504
TI  - Chemical Constituents of Lecythispisonis (Lecythidaceae)--A New Saponin and
      Complete 1H and 13C Chemical Shift Assignments.
AB  - A novel triterpenoid saponin 3-O-beta-D-glucuronopyranosyl-(1' --> 3)
      2alpha,19alpha-dihydroxyolean-12-en-28-oic acid [3-O-beta-D-glucuronopyranosyl
      (1' --> 3)-arjunic acid, 1], ten known compounds [six triterpenoids: alpha-amyrin
      (2), beta-amyrin (3), germanicol (4), lupeol (5), friedelin (6), friedelanol (7);
      four steroids--campesterol (8), stigmasterol (9), sitosterol (10), cholesterol
      (11)], and a long chain alcohol n-eicosan-1-ol (12) were identified in the bark
      of Lecythis pisonis. The structures were established by 1D and 2D NMR
      spectroscopy (1H and 13C-NMR, DEPTQ, 1H-1H-COSY, NOESY, HSQC and HMBC), low (CG
      MS) and high resolution mass spectrometry (HR-ESI-MS), and infrared (IR) spectral
      data involving comparison with the literature.

PMID- 26197505
TI  - Oleanane-type Triterpene Saponins from Glochidion glomerulatum.
AB  - Two new oleanane-type triterpene saponins, named glomeruloside I (1) and
      glomeruloside II (2), were isolated from the leaves of Glochidion glomerulatum
      (Miq.) Boerl. Their structures were determined by extensive spectroscopic
      methods, including 1D- and 2D-NMR, MS data, and chemical methods.

PMID- 26197506
TI  - Cucumarioside E from the Far Eastern Sea Cucumber Cucumaria japonica
      (Cucumariidae, Dendrochirotida), New Minor Monosulfated Holostane Triterpene
      Pentaoside with Glucose as the Second Monosaccharide Residue.
AB  - New minor triterpene glycoside, cucumarioside E (1) has been isolated from the
      Far Eastern sea cucumber Cucumaria japonica. The structure of the glycoside was
      elucidated by 2D-NMR specroscopy and mass-spectrometry. The glycoside has glucose
      instead of quinovose as the second monosaccharide residue and xylose as third
      monosaccharide residue that is unique structural feature for triterpene
      glycosides carbohydrate chains from sea cucumbers belonging to the genus
      Cucumaria.

PMID- 26197507
TI  - Structure Revision of Two Polyoxygenated Sterols from the Marine Sponge
      Neofibularia nolitangere.
AB  - Careful reexamination of the published 1H- and 13C-NMR spectral data of (24S)-24
      ethylcholest-8-ene-3beta,5alpha,6beta,7alpha-tetraol (1) and (24S)-24
      ethylcholest-8(14)-ene-3beta,5alpha,6beta,7alpha-tetraol (2), isolated from the
      marine sponge Neofibularia nolitangere, indicates that, in reality, compounds 1
      and 2 are (24S)-5alpha,6alpha- epoxy-24-ethylcholest-8-ene-3beta,7alpha-diol (9)
      and (24S)-5alpha,6alpha-epoxy-24-ethylcholest-(14)-ene-3beta,7alpha-dio (10),
      respectively.

PMID- 26197508
TI  - Ergosterol of Cordyceps militaris Attenuates LPS Induced Inflammation in BV2
      Microglia Cells.
AB  - Different solvent extracts of Cordyceps militaris stroma powder were tested for
      cell viability and inhibition of nitric oxide (NO) production in
      lipopolysaccharide (LPS) triggered BV2 microglia cells. Chemical investigation of
      the ethyl acetate fraction resulted in an enriched ergosterol sub-fraction CE3.
      The BV2 cells showed no cytotoxic effects when treated with the ethyl acetate
      fraction and sub-fraction CE3 at concentrations of 0.1 MUg/mL - 100 MUg/mL
      compared with the control. At 10 MUg/mL, the ethyl acetate fraction and sub
      fraction CE3 had the highest reduction of 48.0% and 44.7% of nitric oxide
      production, respectively. The major compound in sub-fraction CE3 was ergosterol,
      identified by GCMS, and the purity was checked by HPLC. Further, the reduction of
      nitric oxide in LPS triggered BV2 cells was about three fold higher when compared
      with the control commercial ergosterol.

PMID- 26197509
TI  - Two Novel Spirostene Glycosides from Selaginella chrysocaulos and their
      Chemotaxonomic Significance.
AB  - During an investigation of the Indian heterosporous fern Selaginella
      chrysocaulos, two novel C28 spirostene monosides, chrysocauloside A and B were
      identified. Chrysocauloside A (1beta,3beta-dihydroxy-20S,22R-spirost-5-ene-1-yl
      beta-D-glucopyranoside) and chrysocauloside B (1beta,3beta-dihydroxy-20S,22R
      spirost-5-ene-1-yl beta-D-galactopyranoside) are O-glycosylated at C-1 and each
      bear a methyl group at C-24 and C-25. Spectroscopic (NMR) and MS data for the new
      compounds are given and the taxonomic significance of the occurrence of
      spirostenes in the group of Lycophyta is discussed.

PMID- 26197510
TI  - Anti-Acetylcholinesterase Alkaloids from Annona glabra Leaf.
AB  - Bioassay guided fractionation and separation of the EtOH extract of Annona glabra
      leaf against acetylcholinesterse led to the characterization of 15 alkaloids.
      Among them, (-)-actinodaphnine (2) and (-)-(6aS,7R)-7-hydroxyactinodaphnine (9)
      are new aporphines, although (+)-2 and (+/-)-2 have been found in several plants.
      Their structures were established by spectroscopic analysis. (-)-Anolobine (5)
      and (-)-roemeroline (8) showed moderate inhibitory activity against eel
      acetylcholinesterase with IC50 values of 22.4 and 26.3 MUM, respectively.

PMID- 26197511
TI  - Increased Oxidative Stress in Cultured 3T3-L1 Cells was Attenuated by Berberine
      Treatment.
AB  - The 3T3-L1 cell line is one of the most well-characterized and reliable models
      for studying adipocytes. Increased oxidative stress in accumulated fat was found
      in 3T3-L1 cells. Berberine, an isoquinoline alkaloid, could suppress fat
      deposition in 3T3-L1 cells; however, whether berberine suppresses increased
      oxidative stress is not well known. In this study, we observed the effect of
      berberine on increased oxidative stress in 3T3-L1 cells. 3T3-L1 cells were
      cultured and treated with berberine (5-20 MUM) from day 3 to day 8. We confirmed
      that berberine markedly inhibited fat accumulation and lipid droplets in 3T3-L1
      adipocytes and decreased triglyceride content. Berberine inhibited increased
      oxidative stress in 3T3-L1 cells by suppressing reactive oxygen species (ROS)
      production, and increased glutathione peroxidase (GPx) gene expression and GPx
      activity. Berberine also markedly reduced adipokines secreted by adipocytes,
      including leptin and resistin.

PMID- 26197512
TI  - Synthesis and Antimicrobial Activities of 3-Methyl-beta-Carboline Derivatives.
AB  - The beta-carboline alkaloids possess a diverse range of important biochemical
      effects and pharmacological properties. Sixteen 3-methyl-beta-carboline
      derivatives were synthesized from indole formaldehyde and nitroethane via the
      Henry reaction, LAH/THF reduction, the Pictet-Spengler reaction and Pd/C/xylene
      oxidation, including four 1-substituted and twelve 9-substituted 3-methyl- beta
      carboline derivatives. The structures of all the derivatives were confirmed by 1H
      NMR, 13C NMR and ESI-MS. Most of these 3-methyl-beta-carboline derivatives showed
      some antibacterial activity.

PMID- 26197513
TI  - Novel One-step Synthesis of Quinoline-2(1H)-thiones and Selones by Treating 3
      Aryl-3-(2-aminophenyl)-1-propyn-3-ols with a Base and Elemental Sulfur or
      Selenium.
AB  - A one-step conversion of 3-aryl-3-(2-aminophenyl)-1-propyn-3-ols into quinoline
      2(1H)-thiones and quinoline-2(1H)-selones was achieved only by treating the
      substrates with n-butyllithium and either elemental sulfur or selenium,
      respectively. The reactions were assumed to proceed through an intramolecular
      nucleophilic attack of the neighboring amino group to the plausible in situ
      generated reactive species related to chalcogenoketenes. The subsequent mCPBA
      oxidation of quinoline-2(1H)-selones afforded quinolin-2(1H)-ones in high yields.

PMID- 26197514
TI  - Normonanchocidins A, B and D, New Pentacyclic Guanidine Alkaloids from the Far
      Eastern Marine Sponge Monanchora pulchra.
AB  - New pentacyclic guanidine alkaloids, normonanchocidins A, B and D (1-3) along
      with the earlier known monanchocidin A were isolated from the Far-Eastern marine
      sponge Monanchora pulchra. Structures of 1-3 were elucidated using ID- and 2D-NMR
      spectroscopic and mass spectrometric data. Compound 1 and a mixture of 2 and 3
      (1:1) exhibited cytotoxic activities against human leukemia THP-1 cells with IC50
      values of 2.1 MUM and 3.7 MUM, respectively, and against cervix epithelial
      carcinoma HeLa cells with IC50 of 3.8 MUM and 6.8 MUM, respectively.

PMID- 26197515
TI  - Computational and Investigative Study of Flavonoids Active Against Typanosoma
      cruzi and Leishmania spp.
AB  - Flavonoid compounds active against Trypanosoma cruzi and Leishmania species were
      submitted to several methodologies in silico: docking with the enzymes cruzain
      and trypanothione reductase (from T. cruzi), and N-myristoyltransferase,
      dihydroorotate dehydrogenase, and trypanothiona reductase (from Leishmania spp).
      Molecular maps of the complexes and the ligands were calculated. In order to
      compare and evaluate the antioxidant activity of the flavonoids with their
      antiprotozoal activity, quantum parameters were calculated. Considering the
      energies, interactions, and hydrophobic surfaces calculated, the flavonoids
      chrysin dimethyl ether against T. cruzi, and ladanein against Leishmania sp.
      presented the best results. The antioxidant activity did not show any correlation
      with anti-parasitic activity; only chrysin and its dimethyl ether showed
      favorable anti-parasitic results. This study hopes to contribute to existing
      research on these natural products against these tropical parasites.

PMID- 26197516
TI  - Two New Secondary Metabolites from Tephrosia purpurea.
AB  - Further investigation of Tephrosia purpurea led to the isolation of a new
      prenylated flavone, isoglabratephrin B (1) and a new 1,2-ethanedione benzofuran
      derivative, purpdione B (2). The structures of the new isolates were elucidated
      on the basis of extensive spectroscopic analysis.

PMID- 26197517
TI  - Regioselective Glycosylation of 3-, 5-, 6-, and 7-Hydroxyflavones by Cultured
      Plant Cells.
AB  - Regioselective glycosylation of 3-, 5-, 6-, and 7-hydroxyflavones was
      investigated using cultured plant cells of Eucalyptus perriniana and Phytolacca
      americana as biocatalysts. 3- and 7-Hydroxyflavones were practically glycosylated
      into the corresponding beta-D-glucosides by E. perriniana and P. americana.

PMID- 26197518
TI  - Unusual Flavonoid Glycosides from the Hawaiian Tree Metrosideros polymorpha.
AB  - Metrosideros polymorpha is a highly variable and widely-distributed tree native
      to the Hawaiian islands. We describe here the isolation of two new gossypetin
      derivatives and three new C-methylated flavonol glycosides, which are highly
      uncommon and may prove to be useful chemotaxonomic markers for the species. In
      addition, a wide range of known flavonoid glycosides, chalcones, and terpenoids
      were isolated alongside the new compounds.

PMID- 26197519
TI  - Anti-inflammatory Flavonoids Isolated from Passiflora foetida.
AB  - In this study, we evaluated the anti-inflammatory activity of the soluble ethyl
      acetate fraction and chemical components of the stem bark of Passiflora foetida
      (Passifloraceae). Ten flavonoids (1-10) were isolated by various chromatographic
      techniques, and their structures were determined based on spectroscopic analyses
      by using nuclear magnetic resonance (NMR). Luteolin (2) and chrysoeriol (3)
      showed the most potent inhibition of nitric oxide (NO) production in macrophage
      cell line, RAW264.7, with half maximal inhibitor concentration (IC50) values of
      1.2 and 3.1 MUM, respectively. These compounds suppressed lipopolysaccharide
      (LPS)-induced inducible NO synthase (iNOS) expression at the transcription level.
      Our research indicates that the stem bark of P. foetida has significant anti
      inflammatory properties, suggesting that its flavonoids may have anti
      inflammatory benefits.

PMID- 26197520
TI  - Clovamide and Flavonoids from Leaves of Trifolium pratense and T. pratense subsp.
      nivale Grown in Italy.
AB  - The phenolic content and composition in leaves of Trifolium pratense (red clover)
      and T. pratense subsp. nivale (snow clover) grown in Italy were evaluated by
      means of ultraperformance liquid chromatography (UPLC) coupled with photodiode
      array and mass spectrometry detectors. Compound identification was based on UV
      and MS data comparing results with those of reference compounds. Quantitative
      evaluation of all detected compounds was based on calibration curves obtained
      with available standards. Several phenolics were identified in both extracts,
      including clovamide, flavonols and isoflavones as their glycosilated and
      malonated derivatives. The total phenolic content was higher in red clover (53.7
      +/- 2.2 mg/g dry weight) than in snow clover (44.4 +/- 4.9 mg/g dry weight). Red
      clover contained higher amounts of clovamide and isoflavones (15.6 +/- 0.6 and
      24.6 +/- 1.6 mg/g dry weight, respectively) than snow clover (8.2 +/- 0.1 mg/g
      and 16.9 +/- 0.4 mg/g dry weight, respectively), while flavonols were quantified
      almost in the same amount in both extracts (13.2 +/- 0.6 mg/g and 15.8 +/- 0.6
      mg/g dry weight in red clover and snow clover, respectively). Red clover was
      characterized by the presence of quercetin, formononetin and biochanin A
      derivatives as the most abundant flavonoids, whereas snow clover was
      characterized by higher amounts of quercetin and prunetin derivatives. This
      investigation, conducted for the first time on phenolics from T. pratense subsp.
      nivale, revealed the presence in this plant of several flavonoid derivatives the
      same as in T. pratense. The higher amount of prunetin in snow clover suggest a
      possible role of this isoflavone as a chemotaxonomic marker for this subspecies.
      Moreover, snow clover may represent an interesting new source of natural
      isoflavones with a different concentration pattern than in red clover.

PMID- 26197521
TI  - Water Extract of Mentha x villosa: Phenolic Fingerprint and Effect on Ischemia
      Reperfusion Injury.
AB  - Qualitative analysis of the water extract of Mentha x villosa Huds. leaves was
      performed by liquid chromatography mass spectrometry (LC-MS/MS) and quantitative
      analysis was made by reverse-phase liquid chromatography coupled with photodiode
      array detection (LC-DAD). Sixteen phenolic compounds were identified and
      quantified consisting of 8 phenolic acids/derivatives and 8 flavonoid glycosides
      (quinic acid, chlorogenic acid, coumaroyl-hexoside, caffeic acid, coumaroylquinic
      acid, lithospermic acid, rosmarinic acid, salvianolic acid A, luteolin-7-O
      glucuronide, luteolin-7-O-glucoside, luteolin-7-O-rutinoside, eriodictyol-7-O
      rutinoside, apigenin-7-O-glucuronide, kaempferol-3-O-glucuronide, chrysoeriol-7-O
      rutinoside, and hesperetin-7-O-rutinoside). Luteolin-7- O-rutinoside (25.6 +/-
      0.7 mg/g dry extract) and rosmarinic acid (17.9 +/- 0.4 mg/g dry extract) were
      the most abundant. High antioxidant activity of this phenolic-rich water extract
      was confirmed in vitro by DPPH and ABTS tests and ex vivo in the ischemia
      reperfusion injured rat superior mesenteric artery. Thus, the water extract of M.
      x villosa leaves seems to be a promising agent in prevention of tissue injury
      caused by oxidative stress.

PMID- 26197522
TI  - Distribution and Taxonomic Significance of Secondary Metabolites Occurring in the
      Methanol Extracts of the Stonecrops (Sedum L., Crassulaceae) from the Central
      Balkan Peninsula.
AB  - The present study is engaged in the chemical composition of methanol extracts of
      Sedum taxa from the central part of the Balkan Peninsula, and representatives
      from other genera of Crassulaceae (Crassula, Echeveria and Kalanchoe) considered
      as out-groups. The chemical composition of extracts was determined by HPLC
      analysis, according to retention time of standards and characteristic absorption
      spectra of components. Identified components were considered as original
      variables with possible chemotaxonomic significance. Relationships of examined
      plant samples were investigated by agglomerative hierarchical cluster analysis
      (AHC). The obtained results showed how the distribution of methanol extract
      components (mostly phenolics) affected grouping of the examined samples. The
      obtained clustering showed satisfactory grouping of the examined samples, among
      which some representatives of the Sedum series, Rupestria and Magellensia, are
      the most remote. The out-group samples were not clearly singled out with regard
      to Sedum samples as expected; this especially applies to samples of Crassula
      ovata and Echeveria lilacina, while Kalanchoe daigremontiana was more separated
      from most of the Sedum samples.

PMID- 26197523
TI  - In vitro Xanthine Oxidase Inhibitory Studies of Lippia nodiflora and Isolated
      Flavonoids and Phenylethanoid Glycosides as Potential Uric Acid-lowering Agents.
AB  - Lippia nodiflora has been traditionally used for treatment of knee joint pain.
      Hitherto, no studies have been reported on the effective use of L. nodiflora
      against hyperuricemia, gout or other metabolic disorders. In this present study,
      L. nodiflora was examined for its ability to lower uric acid levels using an in
      vitro xanthine oxidase inhibitory assay. The whole plant methanolic extract was
      subjected to bioactivity-guided fractionation to yield 4 fractions (F1-F4). F3
      displayed the highest potency and was further purified by column chromatography
      to afford two phenylethanoid glycosides, arenarioside (1) and verbascoside (2),
      and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4),
      and nodifloretin (5). These compounds inhibited xanthine oxidase activity, with
      IC50 values between 7.52 +/- 0.01 and 130.00 +/- 2.25 MUM, of which 3 was the
      most potent. In contrast, allopurinol, serving as a positive control, was 0.22 +/
      0.00 MUM. Thus, L. nodiflora, and its chemical constituents are worthy of
      further studies as potential anti-hyperuricemic agents.

PMID- 26197524
TI  - Enzymatic Synthesis of Quercetin Monoglucopyranoside and Maltooligosaccharides.
AB  - Quercetin 3-O-beta-monoglucopyranoside and quercetin 3-O-beta
      maltooligosaccharide were synthesized from quercetin using glucosyltransferase-3
      from Phytolacca americana and cyclodextrin glucanotransferase.

PMID- 26197525
TI  - Polyurethane Microstructures--a Good or Bad in vitro Partner for the Isoflavone
      Genistein?
AB  - In recent years polyurethane microstructures (PM) have gained increasing
      attention in the pharmaceutical field due to the importance of their practical
      application. Since finding that such a formulation with genistein could improve
      its applications, we have conducted a preliminary study regarding the in vitro
      antiproliferative (MCF7, MDA-MB-231 and T47D) and antimicrobial (Staphylococcus
      aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis (D),
      Bacillus subtilis, B. cereus, and Candida albicans) activity in order to test
      whether polyurethane micro structuresre present a good option for further
      modulation of genistein's bioavailability. It was concluded that the polyurethane
      micro structures are a bad in vitro partner for the isoflavone genistein.

PMID- 26197526
TI  - Chemical Constituents of the Underground Parts of Iris florentina and their
      Cytotoxic Activity.
AB  - Three new isoflavonoid glycosides (1, 5, and 9) and 10 known compounds (2-4, 6-8,
      and 10-13) were isolated from the underground parts of Iris florentina
      (Iridaceae). The structures of the new compounds were determined based on
      extensive spectroscopic data and the results of hydrolytic cleavage. The isolated
      compounds and the aglycones were evaluated for cytotoxic activity against HL-60
      human promyelocytic leukemia cells. Compound 12 induced apoptotic cell death in
      the HL-60 cells.

PMID- 26197527
TI  - Synthesis of Arecatannin A1 from Dimeric Epicatechin Electrophile.
AB  - Synthesis of arrecatannin A1 (1) was accomplished from dimeric epicatechin
      electrophile, which was prepared by Zn(OTf)2 mediated self-condensation, and
      monomeric catechin nucleophile. The condensation was successfully worked using
      Yb(OTf)3 as a Lewis acid in good yield.

PMID- 26197528
TI  - Anthocyanin Profile and Antioxidant Activity of Various Berries Cultivated in
      Korea.
AB  - This study examined the anthocyanin composition and antioxidant activity of
      various berries cultivated in Korea: blueberry, crowberry, Korean black
      raspberry, mulberry, and strawberry. The anthocyanins in berries were identified
      by high-performance liquid chromatography (HPLC) analysis, and each component was
      quantitatively analyzed. Furthermore, the antioxidant activity of berries was
      evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging,
      2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation
      decolorization, oxygen radical absorbance capacity (ORAC), and ferric ion
      reducing antioxidant (FRAP) assays. The results revealed that the total content
      of anthocyanins in crowberry was 35.1 mg/g of extract, which was higher than that
      in the other four major berry species (1.9-27.7 mg/g of extract). Nineteen
      anthocyanins were identified in the various berries. The major anthocyanins of
      crowberry were cyanidin-3-galactoside and delphinidin-3-galactoside, and those
      from Korean black raspberry were cyanidin-3-rutinoside and cyanidin-3
      sambubioside-5-rhamnoside. These two berries also had relatively strong
      antioxidant activity accompanied by high total polyphenol contents. Thus,
      consumption of crowberry and Korean black raspberry may be beneficial in reducing
      the risk of developing lifestyle-related chronic diseases because of their strong
      antioxidant activity.

PMID- 26197529
TI  - Metabolite Fingerprinting of Eugenia jambolana Fruit Pulp Extracts using NMR,
      HPLC-PDA-MS, GC-MS, MALDI-TOF-MS and ESI-MS/MS Spectrometry.
AB  - Eugenia jambolana, commonly known as 'jamun' or Indian blackberry, is an
      important source of bioactive compounds. All parts of the plant like stem bark,
      leaves, flower, fruit pulp and seeds are traditionally used for many diseases.
      Metabolite profiling in medicinally important plants is critical to resolve the
      problems associated with standardization and quality control. Metabolite
      profiling of the fruit pulp of Jamun was performed by NMR, HPLC, MS, GC-MS and
      MALDI-TOF mass spectrometry. These hyphenated techniques helped in the
      identification of 68 chemically-diverse metabolites of the fruit pulp. These
      include anthocyanins, anthocyanidins, sugars, phenolics and volatile compounds.
      Five extracts of fruit pulp were prepared i.e. hexane, chloroform, ethylacetate,
      butanol and aqueous methanolic. Twenty-five metabolites identified and quantified
      in the n-butanol and aqueous-methanolic extracts of ripe jamun fruit by qNMR. LC
      PDA-MS and MALDI-TOF spectrometry helped in deciphering thirty-nine metabolites
      out of which thirteen were quantified.

PMID- 26197530
TI  - Flavonoids and Phenolic Acids in Methanolic Extracts, Infusions and Tinctures
      from Commercial Samples of Lemon Balm.
AB  - The aim of this study was to quantify the levels of flavonoids (rutin, myricetin,
      quercetin, kaempferol) and phenolic acids (gallic, p-coumaric, rosmarinic,
      syringic, caffeic, chlorogenic, ellagic, ferulic) in lemon balm (Melissa
      officinalis L.) commonly used as a culinary, aromatic and medicinal herb. A rapid
      and reliable HPLC procedure was developed to determine the phenolic compounds in
      methanolic extracts, infusions and tinctures prepared from lemon balm. Except for
      myricetin and quercetin, as well as ellagic, gallic and rosmarinic acids, higher
      levels of the analytes under study were determined in the methanolic extracts (up
      to 22 mg/g of dry weight, DW), than in infusions (up to 5 mg/g DW). Tinctures
      were the poorest in flavonoids and phenolic acids (below 550 MUg/g DW), except
      for ellagic and rosmarinic acids, which were quantified in tinctures at higher
      levels (mg/g DW). To sum up, the flavonoids were extracted more effectively in
      the infusions and tinctures than the phenolic acids. Statistically significant
      correlations were found between phenolic acids, possibly owing to similar
      biochemical pathways of the compounds. The hierarchical cluster and principal
      component analyses have also shown that the samples of lemon balm could be
      differentiated based on the levels of flavonoids and phenolic acids.

PMID- 26197531
TI  - RP-HPLC-DAD-MS(n) Analysis and Butyrylcholinesterase Inhibitory Activity of
      Barbacenia blanchetii Extracts.
AB  - High-performance liquid chromatography (HPLC) coupled to a diode-array detector
      (DAD) and electrospray ionization mass spectrometry (MS) was applied for the
      separation and identification of phenolic compounds in the n-hexane, ethyl
      acetate and methanol crude extract of Barbacenia blanchetii. The MS, MSn and UV
      data together with chemosystematic evidence allowed the structural
      characterization of five compounds: tricin, chrysoeriol, epi-gallocatechin,
      kaempferol 3-O-glucoside and caffeoylquinic acid. At the same time, these
      extracts were evaluated against butyrylcholinesterase using Ellman's method. All
      extracts inhibited BuChE in a concentration-dependent form; however, the methanol
      extract showed a better effect that the other extracts. These compounds have been
      identified previously in the Velloziaceae family, but for the first time as
      constituents of B. blanchetii.

PMID- 26197532
TI  - Flavonoids and Other Phenolic Compounds in Needles of Pinus peuce and Other Pine
      Species from the Macedonian Flora.
AB  - Flavonoids and other phenolic compounds in young needles of four pine species,
      Pinus peuce, P. nigra, P. mugo and P. sylvestris from the Macedonian flora were
      investigated. The amount of total phenols and total flavonoids were determined
      using Folin-Ciocalteau and aluminum chloride assay, respectively. The obtained
      results revealed that the total phenolic content (TPC) and total flavonoids
      content (TFC) varied among different pine species ranging from 9.8 to 14.0 mg
      GAE/g and from 3.3 to 7.2 mg CE/g of dried plant material, respectively.
      Qualitative analysis of flavonoids and other phenolic components was made by a LC
      DAD/ESI-MS(n) optimized chromatographic method. A total of 17 phenolic components
      were identified and classified as: acids (2), procyanidins (2) and flavonoid
      glycosides (13). The most prevalent components were flavonoid glycosides,
      especially flavonols and methylated flavonols (9). Additionally, 3 components
      were found as acylated flavonol glycosides with ferulic and p-coumaric acid. The
      last one was found not only in esterified form but also in the free form. Only
      one flavone-apigenin glycoside was detected. Procyanidins were identified as
      catechin derivatives, both dimers and trimers.

PMID- 26197533
TI  - Anti-inflammatory, Antioxidant and Antimicrobial Activity Characterization and
      Toxicity Studies of Flowers of "Jarilla", a Medicinal Shrub from Argentina.
AB  - Zuccagnia punctata Cav. (Fabaceae) is an Argentine medicinal aromatic shrub
      (jarilla pispito, puspus, lata and jarilla macho). The chalcones were identified
      as pigments responsible for the yellow color of the flowers. Hydroethanolic
      extracts were obtained both from fresh flowers and from flowers dried by
      lyophilization. The extracts were standardized by their phenolic and flavonoids
      content. Their fingerprints by HPLC-DAD indicated the presence of two chalcones
      as major compounds (2',4'-dihydroxychalcone and 2',4'-dihydroxy-3'
      methoxychalcone). Both extracts showed the same total phenolic, non-flavonoid
      phenolic and flavonoid phenolic content and their phenolic profiles were similar.
      The polyphenolic extracts exhibited antioxidant (free radical scavenging and
      inhibitory activity on lipoperoxidation) and anti-inflammatory (inhibition of
      lipoxygenase and cyclooxygenase enzymes) activities. The flower extracts were
      active against six Candida species with MIC values between 60 and 120 MUg GAE x
      mL(-1) and were also active on methicillin-resistant Staphylococcus aureus (MIC:
      250 MUg GAE x mL(-1)) and Enterococcus faecalis (MIC: 500 MUg GAE x mL(-1)). The
      extracts were neither toxic (Artemia salina test) nor mutagenic (Ames test).
      Jarilla flowers could be considered as a new dietary supplement that could help
      to prevent pathologies associated with oxidative stress and the polyphenolic
      extract obtained from them could be considered as a standardized phytotherapeutic
      product with antimicrobial, antioxidant and anti-inflammatory activities. The aim
      of this work was to determine the pigments responsible for the yellow color of
      the flowers of Z. punctata and to evaluate the functional properties of the
      polyphenolic extract of the flowers. The toxicity (Artemia salina) and mutagenic
      activity (Ames test) of the extract were also evaluated.

PMID- 26197534
TI  - Synthesis of Resveratrol Glycosides by Plant Glucosyltransferase and Cyclodextrin
      Glucanotransferase and Their Neuroprotective Activity.
AB  - Resveratrol was converted by glucosyltransferase from Phytolacca americana into
      its 3- and 4'-O-beta-D-glucosides. On the other hand, further glycosylation of
      resveratrol 4'-O-beta-D-glucoside by cyclodextrin glucanotransferase gave the 4'
      O-beta-maltoside, 4'-O-beta-maltotrioside, 4'-O-beta-maltotetraoside, and 4'-O
      beta- maltopentaoside of resveratrol. The six resveratrol glycosides synthesized
      here showed higher phosphodiesterase inhibitory activity than resveratrol.

PMID- 26197535
TI  - Anti-austeritic Constituents of the Congolese Medicinal Plant Aframomum
      melegueta.
AB  - In the course of our search for anticancer agents based on a novel anti-austerity
      strategy, we found that the CHCl3 extract of the roots of Aflamomum melegueta
      (Zingiberaceae), collected in the Democratic Republic of Congo, killed PANC-1
      human pancreatic cancer cells preferentially in nutrient-deprived medium (NDM).
      Phytochemical investigation of the CHCl3 extract led to the isolation of seven
      known compounds [(-)-buplerol (1), (-)-arctigenin (2), (E)-14-hydroxy-15-norlabda
      8(17),12-dien-16-al (3), labda-8(17),12-dien-15,16-dial (4), 16-oxo-8(17),12(E)
      labdadien-15-oic acid (5), 5-hydroxy-7-methoxyflavone (6), and apigenin (7)]. In
      addition to the previously reported preferentially cytotoxic compound, (-)
      arctigenin (2, PC50 0.5 MUM), (-)-buplerol (1) also displayed potent preferential
      cytotoxicity with a PC50 value of 8.42 MUM and triggered apoptosis-like PANC-1
      cell death in NDM.

PMID- 26197536
TI  - The Lignan-containing Extract of Schisandra chinensis Berries Inhibits the Growth
      of Chlamydia pneumonia.
AB  - The purpose of this study was to investigate the effect and selectivity of an
      extract of Schisandra chinensis berries against Chlamydia pneumoniae and C.
      trachomatis. Among the ethnopharmacological uses of the extract from Schisandrae
      fructus are cough and pneumonia. Therefore we focused on respiratory pathogens.
      The extract completely inhibited the growth of C. pneumoniae strain CV6 at 250
      MUg/mL concentration. The inhibition of C. pneumoniae and C. trachomatis growth
      was dose dependent and established with three different strains. The extract
      inhibited C. pneumoniae production of infectious progeny in a dose dependent
      manner. Chlamydia selectivity was elucidated with growth inhibition measurements
      of three other respiratory bacterial species. A pure compound found in Schisandra
      chinensis berries, schisandrin B at 20.0 MUg/mL concentration inhibited the
      growth of both C. pneumoniae and C. trachomatis. The extract was found to be non
      toxic to the human host cells. These findings highlight the potential of the
      extract from Schisandra chinensis berries as a source for antichlamydial
      compounds.

PMID- 26197537
TI  - A New Aromatic Compound from the Stem Bark of Terminalia catappa.
AB  - A new aromatic compound 3,4,5-trimethoxyphenyl-1-O-(4-sulfo)-beta-D
      glucopyranoside (1), in addition to two triterpenoid saponins (chebuloside II,
      arjunoglucoside II), two triterpenes (arjunolic acid and 3-betulinic acid) and
      sitosterol-3-O-beta-D-glucopyranoside have been isolated from the barks of
      Terminalia catappa. Their structures have been established on the basis of
      spectroscopic techniques (1D/2D NMR) and MS. Their cytotoxicity and
      antiinflammatory activity, together with the antioxidant capacity of compound 1
      were also evaluated.

PMID- 26197538
TI  - Effect of Non-psychotropic Plant-derived Cannabinoids on Bladder Contractility:
      Focus on Cannabigerol.
AB  - There are anecdotal reports that some Cannabis preparations may be useful for
      bladder dysfunctions. Here, we investigated the effect of a number of non-
      psychotropic phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG),
      cannabidivarin (CBDV), Delta9-tetrahydrocannabivarin (THCV) and cannabichromene
      (CBC) on mouse bladder contractility in vitro. CBG, THCV, CBD and CBDV, but not
      CBC, at concentration ranging from 10(-8) M to 10(-4) M, decreased (with similar
      potency), the contractions induced by acetylcholine without significantly
      modifying the contractions induced by electrical stimulation. The rank order of
      efficacy was CBG=THCV>CBD>CBDV. In depth studies on CBG showed that the effect of
      this phytocannabinoid on acetylcholine-induced contractions was not affected by
      CB1 or CB2 receptor antagonists. Additionally, CBG also reduced acetylcholine
      induced contractions in the human bladder.

PMID- 26197539
TI  - In Cell Interactome of Oleocanthal, an Extra Virgin Olive Oil Bioactive
      Component.
AB  - A copper-(I)-catalyzed variation of the Huisgen 1,3-dipolar cycloaddition has
      been applied to lead the in living-cell mass-spectrometry based identification of
      protein targets of oleocanthal, a natural metabolite daily ingested by millions
      of people. Chemical proteomics revealed heat-shock proteins, HSP70 and HSP90, as
      main oleocanthal interactors in living systems. These two proteins are involved
      in cancer development and, thus, our findings could have important outcomes for a
      deep evaluation of the bio-pharmacological significance of oleocanthal.

PMID- 26197541
TI  - Stability of the Ellagitannin Fraction and Antioxidant Capacity of Varietal
      Pomegranate Juices.
AB  - This work aimed to assess the effect of combining two pomegranate (Punica
      granatum L.) cultivars at different rates on the ellagitannin content,
      antioxidant capacity, and total phenolic content of varietal pomegranate juices.
      Widely distinct juices made from Mollar de Elche and Wonderful cultivars were
      used for the elaboration of blended juices. They were stored for 70 days at both
      room and refrigeration temperatures. This study revealed a significant cultivar
      effect on the stability of main pomegranate ellagitannins (punicalagins,
      punicalins, punicalagin-like compound, and ellagic acid derivatives) and on the
      antioxidant capacity measured by the ABTS+ and DPPH* in vitro assays. Blended
      juices enhanced and/or retained the initial ellagitannin content and antioxidant
      capacity of pure juices during storage. Thus, blending varietal juices could be
      suggested as a promising alternative to the development of fresh juices with a
      high, stable phytochemical load.

PMID- 26197540
TI  - Synthesis of epsilon-Viniferin Glycosides by Glucosyltransferase from Phytolacca
      americana and their Inhibitory Activity on Histamine Release from Rat Peritoneal
      Mast Cells.
AB  - Glycosylation of (+)-epsilon-viniferin was investigated using glucosyltransferase
      from Phytolacca americana (PaGT3) as a biocatalyst. (+)-epsilon-Viniferin was
      converted by PaGT3 into its 4b- and 13b-beta-D-glucosides, the inhibitory
      activities on histamine release from rat peritoneal mast cells of which were
      higher than that of (+)-epsilon-viniferin.

PMID- 26197542
TI  - Phthalide Anions in Organic Synthesis. A Direct Total Synthesis of Furomollugin.
AB  - Furomollugin was synthesized in three steps from commercially available starting
      materials using phthalide annulation chemistry.

PMID- 26197543
TI  - Absolute Configuration Assignment of 3',4'-di-O-acylkhellactones Using
      Vibrational Circular Dichroism Exciton Chirality.
AB  - The 3'R,4'R absolute configuration (AC) of the angular-type pyranocoumarins (-)
      3',4'-di-O-acetylkhellactone (2), (-)-4'-O-acetyl-3'-O-angeloylkhellactone (3),
      (+)-3'-O-acetyl-4'-O-isobutyroylkhellactone (4), and (-)-3'-O-angeloyl-4'-O
      senecioylkhellactone (5), isolated from the aerial parts of Prionosciadium
      thapsoides, was assigned by vibrational circular dichroism exciton chirality
      (VCDEC), and confirmed by comparison of their VCD frequencies with those
      calculated using DFT at the B3LYP/DGDZVP level. This again reveals that AC
      assignments based on optical rotation data are not very confident. Evaluation of
      Flack and Hooft parameters obtained after single-crystal X-ray diffraction
      analysis of 3, independently confirmed this AC.

PMID- 26197544
TI  - Antifouling Compounds from the Marine-Derived Fungus Aspergillus terreus
      SCSGAF0162.
AB  - A new cyclic tetrapeptide, asperterrestide B (1), and 11 known compounds (2-12)
      were isolated from a marine-derived fungus Aspergillus terreus SCSGAF0162. The
      structure of 1 was elucidated by spectroscopic analysis, and the absolute
      configuration of 1 was determined by Mosher ester and Marfey's methods. Compounds
      4, 6, and 8 had potent antifouling activity against larvae of the barnacle
      Balanus amphitrite, with EC50 values of 17.1 +/- 1.2, 11.6 +/- 0.6, and 17.1 +/-
      0.8 MUg x mL(-1), respectively.

PMID- 26197545
TI  - Goji Berry: Quality Assessment and Crop Adaptation of Plants Cultivated in
      Tuscany (Italy) by Combination of Carotenoid and DNA Analyses.
AB  - In this study HPLC analysis for the evaluation of carotenoids and DNA barcoding
      are reported for three different samples of Lycium cultivated in Tuscany (Italy).
      These two analytical methods can represent integrative methods for quality
      control of goji, giving also crucial information on the plant adaptation to
      different environments. Hence, carotenoids represent the quality markers proposed
      by the monograph of the European Pharmacopoeia, while DNA barcoding can
      differentiate between species and populations and is useful for the detection of
      the homogeneity of the samples.

PMID- 26197546
TI  - Activity of Vitis vinifera Tendrils Extract Against Phytopathogenic Fungi.
AB  - The in vitro antifungal activity was determined of an ethanolic extract of Vitis
      vinifera L. tendrils (TVV) against ten plant pathogenic fungi, using the agar
      dilution method; activity was shown against all tested fungi. Fusarium species
      were the most sensitive with MIC values ranging from 250 to 300 ppm, while the
      basidiomycete fungus Rhizoctonia solani was the most resistant, with a MIC value
      of 500 ppm. Electrospray ionization tandem mass spectrometry (ESI-MS(n)) was used
      to obtain qualitative information on the main components of TVV. The high amount
      of polyphenolic compounds contained in TVV is likely to contribute significantly
      to its antifungal activity.

PMID- 26197547
TI  - Long-chain Glucosinolates from Arabis turrita: Enzymatic and Non-enzymatic
      Degradations.
AB  - C8-C10 methylsulfinylalkyl glucosinolates (GLs), and C8-C10 methylsulfonylalkyl
      GLs were identified in the seed of Arabis turrita L. by HPLC-MS/ESI analysis of
      intact GLs. Enzymatic (with myrosinase) and non-enzymatic (thermal at 100 degrees
      C, and chemical at different pH) hydrolyses were performed and the volatile
      isolates were analyzed by GC-MS. Only the enzymatic and chemical (pH 10)
      degradations produced volatiles which are originating from GL degradation. GC-MS
      analysis showed the presence of long-chain olefinic isothiocyanates (ITCs) along
      with other the long-chain thiofunctionalized GL breakdown products.

PMID- 26197548
TI  - Aroma of Turmeric: Dependence on the Combination of Groups of Several Odor
      Constituents.
AB  - Turmeric is a popular material that plays an important role in the flavor and
      fragrance industries. Although many compounds have been reported as components of
      turmeric, its aroma profile has not been clarified. Recently we have developed a
      new approach for evaluating the complex odors of materials based on recent
      research on the mechanism of odor recognition. Here we report the characteristic
      aroma properties of turmeric obtained through the investigation of its aroma
      profile. The hexane extract of turmeric had a turmeric-like odor, whereas the
      steam distillate of turmeric had a pungent, non-turmeric-like odor. We carried
      out bulb-to-bulb distillations of the extract and the steam distillate. For the
      hexane extract, two fractions with completely different odors were obtained. One
      was a high boiling point fraction (group A) with a turmeric-like odor, which
      consisted of ar-turmerone and beta-turmerone as the main components, and the
      other was a low boiling point fraction (group B), which consisted of alpha
      curcumene and beta-sesquiphellandrene. In contrast, the bulb-to-bulb distillation
      of the steam distillate gave a fraction (group C) with a very different odor from
      groups A and B. Group C was composed of several kinds of alcohols that were not
      present in groups A and B. These results indicate that the group C fraction
      causes the different, pungent odor of the turmeric oil obtained by steam
      distillation. The variation in the aroma of turmeric depended on the combination
      of these three groups of odor constituents.

PMID- 26197549
TI  - Terpenoids Preserved in Fossils from Miocene-aged Japanese Conifer Wood.
AB  - The compositions of terpenoids from the solvent extracts of two silicified wood
      samples were analyzed using a GC/MS method. Chromatographic analysis showed that
      several biomolecules were preserved unaltered in the Miocene-aged Japanese wood.
      These were alpha-terpineol, alpha-cedrene, thujopsene, widdrol and ferruginol,
      among others. In addition to the bioterpenoids, the fossil woods contained a
      series of geoterpenoids that were generated from their biological precursors
      before and after burial. These were cadalene, daucalene, pseudowiddrene and
      cuparene. The chemical composition of both analyzed fossil samples suggest that
      the silicified woods collected in the Noto Peninsula belong to the Cupressaceae
      family; this was confirmed by morphological analysis. Both samples were
      identified as Taxodioxylon cunninghamioides, which is the most common Miocene
      wood in Japan.

PMID- 26197550
TI  - Can Ozone Alter the Terpenoid Composition and Membrane Integrity of in vitro
      Melissa officinalis Shoots?
AB  - Ozone affects volatile organic compounds that protect plants from biotic and
      abiotic stress. In vitro Melissa officinalis shoots were exposed to ozone (200
      ppb, 3 h) in controlled environmental conditions: leaf pigments, membrane
      integrity and headspace composition were assayed during fumigation and after the
      recovery period (3 h from the beginning of the exposure, FBE). At the end of the
      exposure, no injury was observed in untreated and treated shoots, although an
      evident increase in lipid peroxidation was reported (+38.5 and +37.2% of TBARS
      levels in comparison with controls, respectively after 1 and 3 h FBE). The levels
      of total carotenoids significantly rose as a normal response mechanism to
      oxidative stress. SPME-GS-MS analysis showed that, as a consequence of the
      fumigation, the trends in non-terpenoid compounds increased after 1 and 3 h FBE.
      This suggests that the concentration and the duration of the treatment were
      enough to cause a breakdown of cells (as evidenced by increased TBARS levels) and
      involves an association between volatile products of the lipoxygenase pathway
      (LOX products) and membrane degradation.

PMID- 26197551
TI  - Composition and Chemical Variability of Ivoirian Xylopia staudtii Leaf Oil.
AB  - The chemical composition of a leaf oil sample from Ivoirian Xylopia staudtii
      Engler & Diels (Annonaceae) has been investigated by a combination of
      chromatographic [GC(RI)] and spectroscopic (GC-MS, 13C NMR) techniques. Thirty
      five components that accounted for 91.8% of the whole composition have been
      identified. The oil composition was dominated by the furanoguaiadienes
      furanoguaia-1,4-diene (39.0%) and furanoguaia-1,3-diene(7.5%), and by germacrene
      D (17.5%). The composition of twelve other leaf oil samples demonstrated
      qualitative homogeneity, but quantitative variability. Indeed, the contents of
      the major components varied substantially: furanoguaia-1,4-diene (24.7-51.7%) and
      germacrene D (5.9-24.8%). The composition of X. staudtii leaf oil is close to
      that of X. rubescens leaf oil but varied drastically from those of the essential
      oils isolated from other Xylopia species. 13C NMR spectroscopy appeared as a
      powerful and complementary tool for analysis of sesquiterpene-rich essential
      oils.

PMID- 26197552
TI  - Chemoinformatics Approach to Antibacterial Studies of Essential Oils.
AB  - The chemical composition and antibacterial activity of Nepeta nuda (Lamiaceae)
      essential oil were examined, as well as the association between it and standard
      antibiotics: tetracycline and streptomycin. The antibacterial activities of 1,8
      cineole, the main constituent of N. nuda oil, individually and in combination
      with standard antibiotics were also determined. The interactions of the essential
      oil and 1,8-cineole with antibiotics toward five selected strains were evaluated
      using the microdilution checkerboard assay in combination with chemoinformatics
      methods. Oxygenated monoterpenes were the most abundant compound class in the oil
      (57.8%), with 1,8-cineole (46.0%) as the major compound. The essential oil
      exhibited in vitro antibacterial activity against all tested bacterial strains,
      but the activities were lower than those of the standard antibiotics. The
      combinations N. nuda oil-antibiotic and 1,8-cineole-antibiotic produced a
      predominantly antagonistic interactions. Chemoinformatics survey confirms the
      antagonistic interactions as a consequence of membrane potential/proton motive
      force dissipation. These data indicate cytochrome c oxidase as a target for 1.8
      cineole toxicity action mechanisms.

PMID- 26197553
TI  - Chemical Composition of Nardostachys grandiflora Rhizome Oil from Nepal--A
      Contribution to the Chemotaxonomy and Bioactivity of Nardostachys.
AB  - The essential oil from the dried rhizome of Nardostachys grandiflora, collected
      from Jaljale, Nepal, was obtained in 1.4% yield, and a total of 72 compounds were
      identified constituting 93.8% of the essential oil. The rhizome essential oil of
      N. grandiflora was mostly composed of calarene (9.4%), valerena-4,7(11)-diene
      (7.1%), nardol A (6.0%), 1(10)-aristolen-9beta-ol (11.6%), jatamansone (7.9%),
      valeranal (5.6%), and cis-valerinic acid (5.7%). The chemical composition of N.
      grandiflora rhizome oil from Nepal is qualitatively very different than those
      from Indian, Chinese, and Pakistani Nardostachys essential oils. In this study we
      have evaluated the chemical composition and biological activities of N.
      grandiflora from Nepal. Additionally, 1(10)-aristolen-9beta-ol was isolated and
      the structure determined by NMR, and represents the first report of this compound
      from N. grandiflora. N. grandiflora rhizome oil showed in-vitro antimicrobial
      activity against Bacillus cereus, Escherichia coli, and Candida albicans (MIC =
      156 MUg/mL), as well as in-vitro cytotoxic activity on MCF-7 cells.

PMID- 26197555
TI  - Comparative Chemical Composition and Antioxidant Properties of the Essential Oils
      of three Sideritis libanotica Subspecies.
AB  - The phytochemical composition of the essential oils of three Sideritis libanotica
      subspecies, namely S. libanotica ssp. libanotica, S. libanotica ssp. linearis and
      S. libanotica ssp. michroclamys, all collected in Lebanon, was analyzed by GC and
      GC-MS. The diterpene sideridiol was recognized as the main constituent of both S.
      libanotica ssp. libanotica (50.8%) and S. libanotica ssp. michroclamys (18.4%)
      oils, while hexadecanoic acid (10.5%) prevailed in S. libanotica ssp. linearis.
      The antioxidant activity of the oils was studied in two cell free systems by DPPH
      radical scavenging and ferric ion reduction (FRAP) assays; only S. libanotica
      ssp. linearis showed a moderate activity when assayed by the FRAP test (0.6 +/-
      0.01 mmol TE/mL).

PMID- 26197554
TI  - Chemical Composition and Biological Activity of Essential Oils from Wild Growing
      Aromatic Plant Species of Skimmia laureola and Juniperus macropoda from Western
      Himalaya.
AB  - The Himalayan region is very rich in a great variety of medicinal plants. In this
      investigation the essential oils of two selected species are described for their
      antimicrobial and larvicidal as well as biting deterrent activities.
      Additionally, the odors are characterized. Analyzed by simultaneous GC-MS and GC
      FID, the essential oils' chemical compositions are given. The main components of
      Skimmia laureola oil were linalool and linalyl acetate whereas sabinene was found
      as the main compound for Juniperus macropoda essential oil. Antibacterial testing
      by agar dilution assay revealed highest activity of S. laureola oil against all
      tested bacteria, followed by J. macropoda oil. Antifungal activity was evaluated
      against the strawberry anthracnose causing plant pathogens Colletotrichum
      acutatum, C. fragariae and C. gloeosporioides. Juniperus macropoda essential oil
      indicated higher antifungal activity against all three pathogens than S. laureola
      oil. Both essential oils showed biting deterrent activity above solvent control
      but low larvicidal activity.

PMID- 26197556
TI  - Asplenioideae Species as a Reservoir of Volatile Organic Compounds with Potential
      Therapeutic Properties.
AB  - Twelve French Asplenioideae ferns (genera Asplenium and subgenera Ceterach and
      Phyllitis) were investigated for the first time for volatile organic compounds
      (VOC) using GC-MS. Sixty-two VOC biosynthesized from the lipidic, shikimic,
      terpenic and carotenoid pathways were identified. Several VOC profiles can be
      highlighted from Asplenium jahandiezii and A. xalternifolium with exclusively
      lipidic derivatives to A. onopteris with an equal ratio of lipidic/shikimic
      compounds. Very few terpenes as caryophyllene derivatives were identified, but
      only in A. obovatum subsp. bilotii. The main odorous lipidic derivatives were (E)
      2-decenal (waxy and fatty odor), nonanal (aldehydic and waxy odor with a fresh
      green nuance), (E)-2-heptenal (green odor with a fatty note) and 1-octen-3-ol
      (mushroom-like odor), reported for all species. A few VOC are present in several
      species in high content, i.e., 9-oxononanoic acid used as a precursor for
      biopolymers (19% in A. jahandiezii), 4-hydroxyacetophenone with a sweet and heavy
      floral odor (17.1% in A. onopteris), and 4-hydroxybenzoic acid used as a
      precursor in the synthesis of parabens (11.3% in A. foreziense). Most of the
      identified compounds have pharmacological activities, i.e., octanoic acid as
      antimicrobial, in particular against Salmonellas, with fatty and waxy odor (41.1%
      in A. petrarchae), tetradecanoic acid with trypanocidal activity (13.3% in A.
      obovatum subsp. bilotii), 4-hydroxybenzoic acid (8.7% in A. onopteris) with
      antimicrobial and anti-aging effects, 3,4-dihydroxybenzaldehyde as an inhibitor
      of growth of human cancer cells (6.7% in Ceterach officinarum), and phenylacetic
      acid with antifungal and antibacterial activities (5.8% in A. onopteris).
      Propionylfilicinic acid was identified in the twelve species. The broad spectrum
      of odorous and bioactive VOC identified from the Asplenium, Ceterach and
      Phyllitis species are indeed of great interest to the cosmetic and food
      industries.

PMID- 26197557
TI  - Composition and Comprehensive Antioxidant Activity of Ginger (Zingiber
      officinale) Essential Oil from Ecuador.
AB  - In the present study, the chemical composition and antioxidant potential of an
      essential oil of ginger rhizomes from Ecuador was elucidated. The analysis of the
      essential oil by GC/FID/MS resulted in identification of 71 compounds, of which
      the main are citral (geranial 10.5% and neral 9.1%), alpha-zingiberene (17.4%),
      camphene (7.8%), alpha-farnesene (6.8%) and beta-sesquiphellandrene (6.7%). The
      in vitro antioxidant activity of the essential oil expressed by IC50 in
      descending order is: hydroxyl radical (OH*) scavenging (0.0065 MUg/mL) >
      chelating capacity (0.822 MUg/mL) > 2,2-azino-bis-3-ethylbenzothiazoline-6
      sulfonic acid radical cation (ABTS*+) scavenging (3.94 MUg/mL) > xanthine oxidase
      inhibition (138.0 MUg/mL) > oxygen radical (O2*) scavenging (404.0 MUg/mL) > 2,2-
      diphenyl-1-picrylhydrazyl radical (DPPH*) scavenging (675 MUg/mL). Lipid
      peroxidation inhibition of the essential oil was less efficient than
      butylhydroxytoluol (BHT) in both stages, i.e. hydroperoxide and malondialdehyde
      formation. In vivo studies in Saccharomyces cerevisiae demonstrated a significant
      dose-dependent increase in antioxidant marker enzymes, superoxide dismutase
      (SOD), catalase (CAT) and glutathione peroxidase (GPx), blocking the oxidation
      processes in yeast cells. Moreover, ginger essential oil in concentrations of 1.6
      mg/mL increases the viability of cells to oxidative stress induced by H2O2.

PMID- 26197558
TI  - Chemical Components of Four Essential Oils in Aromatherapy Recipe.
AB  - This study focused on characterization of the chemical components of an
      aromatherapy recipe. The formulation consisted of four blended essential oils;
      rosemary oil, eucalyptus oil, pine oil and lime oil (volume ratio 6 : 2 : 1 : 1).
      The single and combination essential oils were identified by gas chromatography
      mass spectrometry (GC-MS). The analysis of GC-MS data revealed that several
      components exist in the mixture. The five most important components of the
      blended essential oils were 1,8-cineole (35.6 %), alpha-pinene (11.1%), limonene
      (9.6%), camphor (8.4%), and camphene (6.6%). The main components of rosemary oil
      were 1,8-cineole (37.3%), alpha-pinene (19.3%), camphor (14.7%), camphene (8.8%),
      and beta-pinene (5.5%); of eucalyptus oil 1,8-cineole (82.6%) followed by
      limonene (7.4%), o-cymene (4.3%), gamma-terpinene (2.7%), and alpha-pinene
      (1.5%); of pine oil terpinolene (26.7%), alpha-terpineol (20.50%), 1-terpineol
      (10.8%), alpha-pinene (6.0%), and gamma-terpineol (5.3%); and of lime oil
      limonene (62.9%), gamma-terpinene (11.5%), alpha-terpineol (7.6%), terpinolene
      (6.0%), and alpha-terpinene (2.8%). The present study provided a theoretical
      basis for the potential application of blended essential oils to be used as an
      aromatherapy essential oil recipe. GC-MS serves as a suitable and reliable method
      for the quality control of the chemical markers.

PMID- 26197559
TI  - Recent Advances in the Synthesis of Stemona Alkaloids.
AB  - Stemona alkaloids, featuring polycyclic structures and interesting bioactivities,
      constitute a distinct class from the Stemonaceae family. In this review, recent
      advances in the synthesis of these unique alkaloids are briefly discussed,
      highlighting the application of novel synthetic strategies to access the core
      structures, as well as creative solutions to the installation of multiple
      stereogenic centers. The literature reviewed in this article covers the
      publications from 2010 to November 2014, a period that witnessed the prosperity
      of the synthesis of Stemona alkaloids.

PMID- 26197560
TI  - Flavonoid Properties in Plant Families Synthesizing Betalain Pigments (Review).
AB  - The anthocyanin pigments are contained in the flowers, fruits, leaves and roots
      of almost plant species. On the other hand, distribution of the betacyanins are
      limited in eight families of the order Caryophyllales, i.e. Aizoaceae,
      Amaranthaceae, Basellaceae, Cactaceae, Didiereaceae, Nyctaginaceae,
      Phytolaccaceae and Portulacaceae. However, other flavonoids, i.e. flavones, C
      glycosylflavones, flavonols, flavanones, dihydroflavonols, chalcones, aurones,
      and flavan and proanthocyanidins, are synthesized in betalain-containing
      families. In this review, distribution and properties of the flavonoids in eight
      betalain-containing families are described.

PMID- 26197561
TI  - Phytochemistry and Pharmacology of the Genus Tovomita.
AB  - The genus Tovomita (Fam. Clusiaceae) comprises 45 species mainly found in
      tropical regions of Central and South America. Most of the species of the title
      genus have been used for centuries as natural remedies. Phytochemicals isolated
      from Tovomita spp. include prenylated and unprenylated benzophenones and
      xanthones. The aim of this review is to examine in detail from a phytochemical
      and pharmacological point of view what is reported in the past and current
      literature about the properties of phytopreparations and individual active
      principles obtained from plants belonging to the Tovomita genus.

PMID- 26197562
TI  - Fungal Phytotoxins with Potential Herbicidal Activity to Control Chenopodium
      album.
AB  - This review deals with the isolation and chemical and biological characterization
      of phytotoxins produced by Ascochyta caulina and Phoma chenopodiicola proposed as
      mycoherbicides for the biological control of Chenopodium album, a worldwide
      spread weed which causes serious problems to some agrarian crops, including sugar
      beet and maize. Studies on the structure activity relationships and on the modes
      of actions of toxins isolated are also described, as well as the optimization of
      analytical methods focused on selection of the best fungal toxin producers. The
      attempts to scale up production of these phytotoxins aimed to obtain sufficient
      amounts for their application in greenhouse and field trials are also reported.

PMID- 26197563
TI  - Essential Oils as "A Cry for Help". A Review.
AB  - This work is an update of a recently published review and is consistently
      referred to this article and recent findings about plants' indirect defense are
      added on. Herbivore induced plant volatiles (HIPVs) and their effects on the
      third trophic level that involves predators and parasitoids are discussed. The
      fact that plants are not passive individuals is confirmed on the basis of several
      studies. Plants can perceive and respond to cues in their environments with
      plastic morphological, physiological and behavioral traits. Plasticity allows
      plants to tailor their defenses to their current and expected risks caused by
      herbivores. The "cry for help" of plants is also observed from the carnivores'
      point of view. The volatile mixture contains crucial information for decisions of
      carnivorous insects. Furthermore, the most important methods to examine the
      behavioral response of carnivorous insects to HIPVs are presented not only in
      laboratory set ups but also in the field. Manipulations of plants by silencing
      genes or over-expressing genes can help to understand mechanisms of indirect
      defense. Various interesting examples of indirect defense reveal the possibility
      to use HIPVs in biological control. Therefore, the application of synthetic
      pesticides, that pollute the environment, may be reduced in the future.

PMID- 26197564
TI  - Near-Infrared Imaging Using a High-Speed Monitoring Near Infrared Hyperspectral
      Camera (Compovision).
AB  - This review paper reports near-infrared (NIR) imaging studies using a newly
      developed NIR camera, Compovision. Compovision can measure a significantly wide
      area of 150 mmX 250 mm at high speed of between 2 and 5 s. It enables a wide
      spectral region measurement in the 1,000-2,350 nm range at 6 nm intervals. We
      investigated the potential of Compovision in the applications to industrial
      problems such as the evaluation of pharmaceutical tablets and polymers. Our
      studies have demonstrated that NIR imaging based on Compovision can solve several
      issues such as long acquisition times and relatively low sensitivity of
      detection. NIR imaging with Compovision is strongly expected to be applied not
      only to pharmaceutical tablet monitoring and polymer characterization but also to
      various applications such as those to food products, biomedical substances and
      organic and inorganic materials.

PMID- 26197565
TI  - [Study on Characteristics of Terahertz Spectra of Organic Functional Groups].
AB  - Fourier transform infrared (FTIR) was exploited to measure terahertz (THz)
      spectra in the wave number range of 30-300 cm(-1) for saturated straight chain
      organic molecules at room temperature. The results reveal that different organic
      functional groups exhibit different THz spectral characteristics. The absorption
      peaks of vibration modes of organic crystal lattice locate in high frequency
      range of THz, while those of vibration modes of intermolecular hydrogen (H) bonds
      appear in low frequency range of THz. Moreover, a typical absorption peak of
      intermolecular H bonds caused by saturated straight-chain monohydric alcohol
      hydroxyl functional groups locates at 57 cm(-1), while a characteristic
      absorption peak of intermolecular hydrogen bonds caused by triacontanoic acid
      carboxyl functional groups appears at 74 cm(-1). The intermolecular H bonds not
      only result in that the THz absorbing abilities of triacontanol and triacontanoic
      acid are significantly stronger than that of triacontane, but also cause regular
      red-shift and blue-shift of the THz absorption peaks of triacontanoic acid, as
      compared with those of triacontanol. In addition, density functional theory (DFT)
      B3LYP/6-311G(d,p) basis set was employed to simulate the THz spectra of saturated
      straight-chain alkane, alkanol and acid, respectively. The simulation results
      indicate that for the organic molecules with stronger intermolecular H bonds,
      lower consistent degree of the THz spectrum simulated from monomer molecule with
      the THz spectrum experimentally measured will occur. Moreover, the simulation
      results of dimer structures agree well with the measured spectra as compared to
      those simulated from monomer molecule structures. The results presented in this
      work are of great significance not only to the study of the THz spectral
      characteristics of other organic functional groups, but also to the clarification
      of the vibration modes of organic molecules. Particularly, our results are also
      helpful for clarifying the THz response theory of organics, and for exploiting
      the applications of organic materials in THz devices.

PMID- 26197566
TI  - [Construction and Characterization of B850-Only LH2 Energy Transfer System in
      Purple Bacteria].
AB  - To seek microscopic molecular mechanism of energy transfer and complex
      reconstitution in the photosynthesis, the conditions for construction of B850
      only peripheral light-harvesting complex (LH2) and their properties were
      investigated using absorption, fluorescence spectroscopy, molecular sieve
      chromatography, ultrafiltration and sodium dodecylsulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) from the purple bacteria. The results indicated that
      bacteriochlorophylls (BChl) of B800 incubated in 10 mmo . L(-1) Tris-HCl (pH 8.0)
      buffer are selectively released from their binding sites of LH2 of Rhodobacter
      azotoformans (A-LH2) by 0.08% (W/V) SDS. B850-only A-LH2 was constructed after
      removing free BChl mixing with 10% methyl alcohol by ultrafiltration. B850 BChl
      was released after A-LH2 was incubated for 240 min in dark at room temperature
      (RT). While BChl of B800 incubated in pH 1.9 buffer were selectively released
      from their binding sites of LH2 of Rhodopseudomonas palustris (P-LH2). The
      authors acquired two components using molecular sieve chromatography. Free BChl
      of one component was not removed and self-assembled to P-LH2. The other removed
      free BChl and B850-only P-LH2 was constructed. B850 unchanged after P-LH2 was
      incubated. P-LH2 alpha and beta subunits have different molecular weights, but
      those of A-LH2 are in the contrary. It is concluded that B850-only P-LH2 is more
      stable than A-LH2. The enigmatic split of the B800 absorption band was not
      observed in these LH2, but we acquired two kinds of B800-released LH2 from
      Rhodopseudomonas palustris. The authors' results may provide a new light to
      separate homogeneous Apoprotein LH2.

PMID- 26197567
TI  - [A Detection Technique for Gas Concentration Based on the Spectral Line Shape
      Function].
AB  - The methods that can rapidly and precisely measure concentrations of various
      gases have extensive applications in the fields such as air quality analysis,
      environmental pollution detection, and so on. The gas detection method based on
      the tunable laser absorption spectroscopy is considered a promising technique.
      For the infrared spectrum detection techniques, the line shape function of an
      absorption spectrum of a gas is an important parameter in qualitative and
      quantitative analysis of a gas. Specifically, how to obtain the line shape
      function of an absorption spectrum of a gas quickly and accurately is a key
      problem in the gas detection fields. In this paper we analyzed several existing
      line shape functions and proposed a method to calculate precisely the line shape
      function of a gas, and investigated the relation between the gas concentration
      and the peak value of a line shape function. Then we experimentally measured the
      absorption spectra of an acetylene gas in the wavelength range of 1,515-1,545 nm
      with a tunable laser source and a built-in spectrometer. With Lambert-Beer law we
      calculated the peak values of the line shape function of the gas at the given
      frequencies, and obtained a fitting curve for the line shape function in the
      whole waveband by using a computer program. Comparing the measured results with
      the calculated results of the Voigt function, we found that there was a deviation
      between the experimental results and the calculated results. And we found that
      the measured concentration of the acetylene gas by using the fitting curve of the
      line shape function was more accurate and compatible with the actual situation.
      Hence, the empirical formula for the line shape function obtained from the
      experimental results would be more suitable for the concentration measurement of
      a gas. As the fitting curve for the line shape function of the acetylene gas has
      been deduced from the experiment, the corresponding peak values of the spectral
      lines can be immediately calculated out from the curve and used for the
      measurements of different concentrations of acetylene gases. Therefore, the
      calculation for the line shape function values is greatly simplified. The
      obtained data of the line shape function of the acetylene gas can be used for
      remote sensing of the gas, and the proposed method can also be applied for the
      measurements of line shape functions of other gases.

PMID- 26197568
TI  - [Purification of PTCDA by Vacuum Sublimation and Spectral Test and Analysis].
AB  - The organic semiconductor 3, 4, 9, 10 perylenetetracarboxylic dianhydride (PTCDA)
      with the purity of 97.5% was purified by sublimation to 99.9%. The high-purity
      PTCDA material was measured by mass spectra, infrared spectrum and X-ray
      photoelectron spectroscopy (XPS). Detailed analysis revealed its molecular
      structure, the forming of chemical bond, the vibration modes of atoms in
      equilibrium lattice position, electronic configuration and the shift of binding
      energy of atoms. Based on the infrared spectrum analysis, the molecular structure
      of PTCDA is consisting of perylene core group with five C rings and two
      anhydrides located at both ends of perylene core, which is mainly bonded with
      covalent bond. The stretching vibration of C atoms in the crystal lattice
      dominates in their equilibrium positions. The PTCDA molecules have a large number
      of pi electrons which can move freely; the intermolecular delocalized pi bond
      overlap determines the conductivity of PTCDA. Based on XPS analysis, it can be
      found that there exist two kinds of C atoms with different binding energy: 285.3
      and 288.7 eV, respectively, corresponding to the C atoms in the perylene ring and
      anhydride. In addition, there are two kinds of O atoms, i. e. C==0 and C--O--C,
      whose bonding energy is 531.3 and 533.1 eV, respectively.

PMID- 26197569
TI  - [Synthesis and Luminescence Properties of BiOCL: Dy3+Phosphors for NUV Excited
      White Light-Emitting Diodes].
AB  - Abstract In the present paper, we reported the luminescence properties of
      BiOCl:Dy(3+) and BiOCl:Dy(3+), Li+ phosphor synthesized by conventional solid
      state method. X-ray diffraction (XRD) and excitation and emission spectroscopy
      were used to characterize the samples. Results show that pure tetragonal
      BiOCl:Dy(3+) crystals can be synthesized successfully at 500  degrees C, and Li+
      ion dopant improves the crystallinity of samples furtherly. Under near UV light
      excitation, the samples,give the characteristic luminescence of Dy(3+) ions
      located at 478 (blue) and 574 nm (yellow), which show a low yellow-to-blue
      intensity ratio (Y/B) of Dy(3+) emission and white light emission. Moreover,
      codoping of Li+ ion can realize the enhancement of emission intensity and the
      adjustment of emission color. The characteristics of BiOCl:Dy(3+) phosphor, low
      temperature preparation, good near ultraviolet excitation and white light
      emission make it to a promising near-ultraviolet WLED phosphor.

PMID- 26197570
TI  - [How to Remove Water Absorption Bands Completely from IR Spectra of Aqueous
      Solution].
AB  - Infrared spectral studies of aqueous solution have been severely limited by the
      strong water absorption. Usually, it is very difficult to experimentally achieve
      perfect compensation between the amount of water that contributes to the sample
      and background spectra. In the present paper, we introduced a new method to make
      the infrared bands of water disappear during the measurement of an infrared
      spectrum for aqueous solution. Both background spectrum of the empty ATR cell and
      that of the water on ATR cell are used in sequence. Qualified infrared spectra of
      10% K2CO3 and 10% BSA aqueous solutions were successfully obtained by ATR
      accessory (single-reflection) without water interference. The experimental
      results demonstrated that the new method is fast, effective and powerful. The
      limitation of the new method is also discussed.

PMID- 26197571
TI  - [Spectrum Research on Rheology of High Rank Coal].
AB  - Aiming to discuss the change characteristic of macromolecular structures of high
      rank coal in different rheological conditions, the high rank undeformed coal from
      southern Qinshui basin and the coal after variable temperature and variable
      pressure rheology experiments were investigated and analyzed in detail through
      Fourier transform infrared spectroscopy (FTIR) and laser Raman spectra analysis.
      The result shows that the texture and composition of different types of
      rheological coals under different temperature and pressure exhibit significant
      differences. Experiments of variable temperature and pressure of high rank coal
      (temperature: 300-400  degrees C, confining pressure: 50-100 MPa, strain: less
      than 10% and strain rate: 10(-4)-10(-7) . s(-1) will distort their macromolecular
      structures and recombine the chemistry structures. When the temperature is 300 
      degrees C or 350  degrees C, the high rank coal generates brittle or brittle
      ductile rheology easily, mechanical energy transforms to heat energy, some
      branches and functional groups with weaker bond energy break and fall off, which
      split as dissociative micromolecule, with stress degradation as principal role,
      and stress polycondensation occurs with aromatic, texture increasing. When the
      temperature is up to 400  degrees C, ductile rheology of the high rank coal
      occurs with the secondary defects increasing, mechanical energy transforms to
      strain energy which helps the early shedding small molecules be embedded or
      adsorbed in the defect or on the surface of macromolecular preferentially and
      change the aliphatic and aromatic structures. It is affected by stress
      degradation and polycondensation progress, and the latter is dominated. The
      confining pressure and water injection of coal do not have much effect on the
      macromolecular structure obviously.

PMID- 26197572
TI  - [The Significance of Analysis of Soil from the Surface of Hetao Plain, Inner
      Mongolia with Near Infrared Spectra].
AB  - The technology of near infrared spectrum, marked by its convenience and
      effectiveness, which has been applied extensively in lithological analysis, is
      suitable for component analysis of regional geology, due to its superiority in
      analyzing numerous samples in a relatively short time. Since different mineral
      molecule peaks will show different characters when being analyzed in the near
      infrared spectrum, we can acquire the information about the mineral composition,
      water content, mineral crystallinity and etc. In this passage, the soil from the
      surface of Hetao Plain has been analyzed, and in this case, we can obtain the
      information about the mineral composition, water content, mineral crystallinity
      and etc. Referring the features of local environment and climate, we could
      surmise the source of the minerals in soil and the environment where they formed.
      The result not only consummates the geological characterization of Hetao area,
      but also has great significance revealing mechanism of soil-formation in Hetao
      area. The result shows that the soil from surface of Hetao Plain is mainly
      composed by altered minerals, such as kaolinite, smectite, ledikite, muscovite
      etc, and is presumed to be from acidic rock mass of the Yinshan mountains. The
      passage also indicates that the Yinshan mountains have great impact on the
      formation of the soil on Hetao Plain in the aspect of climate, for example,
      though the climate of inner Mongolia is continental arid climate, enough rainfall
      and the substantial differences in mean annual precipitation ensure the
      relatively moist environment in this area, and make the sediments altered
      adequately, proposing new aspects about exploring the mechanism of the soil
      formation in Hetao area.

PMID- 26197573
TI  - Application of Fourier Transform Infrared Spectra (FTIR) Fingerprint in the
      Quality Control of Mineral Chinese Medicine Limonitum.
AB  - In the present paper, the fingerprint of Limonitum (a mineral Chinese medicine)
      by FTIR was established, and the spectrograms among crude samples, processed one
      and the adulterant sample were compared. Eighteen batches of Limonitum samples
      from different production areas were analyzed and the angle cosine value of
      transmittance (%) of common peaks was calculated to get the similarity of the
      FTIR fingerprints. The result showed that the similarities and the coefficients
      of the samples were all more than 0.90. The processed samples revealed
      significant differences compared with the crude one. This study analyzed the
      composition characteristics of Limonitum in FTIR fingerprint, and it was simple
      and fast to distinguish the crude, processed and the counterfeit samples. The
      FTIR fingerprints provide a new method for evaluating the quality of Limonitum.

PMID- 26197574
TI  - [Multidimensional Scaling Linear Regression Applied to FTIR Spectral Quantitative
      Analysis of Clinical Parameters of Human Blood Serum].
AB  - In the present paper it was proposed to establish multidimensional scaling linear
      regression (MDS-MLR) models by combining multidimensional scaling (MDS) with
      multiple linear regression (MLR), in which MDS owns the ability of dimensionality
      reduction on spectral variables. Thus the informative spectral wavelengths can be
      selected for each of the 4 clinical parameters (i. e. glucose, LDL cholesterol,
      triglycerides and urea) by MDS-MLR method, and the effect of spectral colinearity
      can be restrained, so that the calibration models can be optimized. Experiments
      showed that the MDS-MLR models will allow to produce appreciated modeling results
      when combined with the preprocessing method of moving average (MA). The optimized
      models were verified by the samples in validation set, and the validating
      correlation coefficients for each clinical parameter were all upper than 0. 9.
      These results indicated that FTIR predicted values and the biochemical values of
      each clinical parameter were highly correlated, which demonstrated that MDS-MLR
      method has the potential of being applied to the FTIR spectroscopic analysis of
      human serum. FTIR rapid determination technology combined with the MDS-MLR
      modeling method is expected to realize the rapid assessment of human health and
      sub-health level.

PMID- 26197575
TI  - [Quantitative Approach to Melamine Detection in Egg White with Surface-Enhanced
      Raman Spectroscopy].
AB  - Due to the harmfulness of melamine to human, the quantitative detection of
      melamine in egg is very necessary. In the present study, the surface enhanced
      Raman spectra technology combined with chemometric analysis method was used to
      conduct melamine quantitative detection in egg white. Firstly, the melamine egg
      sample could be got by the method of artificial feeding hens usingdifferent
      feeding formulation. Then the surface enhanced Raman spectra of egg white was
      determined using portable Raman spectroscopy (Opto Trace RamTracer-200) and Raman
      enhancement reagents, and the melamine content within the white eggs was measured
      with gas chromatography mass spectrometry technology. The software of Raman
      Analyzer was used for baseline correction of Raman spectra. The correlation
      coefficient method was used to choose 320 spectral variables from the surface
      enhanced Raman spectroscopy as input variables to establish partial least squares
      quantitative calibration model . And the peaks-decomposition method was used to
      establish peaks-decomposition quantitative calibration model. Both models
      selected 90 and 44 samples respectively as calibration sets and validation sets
      during model establishment, and both models achieved good prediction effect. The
      determination coefficient between predicted values of partial least squares
      quantitative calibration model and measured values of gas chromatography mass
      spectrometry was 0.856, and root mean square error of prediction was 1.547. The
      determination coefficient was 0.947 and RMSEP was 0.893 for the peaks
      decomposition quantitative calibration model. This study demonstrated that the
      method can effectively quantitatively detect melamine in eggs. Testing a sample
      only takes 15 minutes, which can provide a new way for the melamine egg
      detection.

PMID- 26197576
TI  - [Raman Spectroscopic Study on the Determination of SO4(2-) Concentration in
      Aqueous Solution under High Temperature and Pressure].
AB  - In the present work, the Raman spectra of SO4(2-) ions in aqueous solutions were
      studied. The quantitative analysis shows that there is a significant correlation
      between the Raman intensity ratio(R) and the SO4(2-) concentration. The SO4(2-)
      concentration in aqueous solution at ambient temperature and pressure can be
      determined by the Raman intensity according to the linear fitting equation c
      (SO4(2-) = 4.779 6R (r2 = 0.999 4). Furthermore, the research proves that the
      temperature and pressure will af- fect the relationship between the Raman
      intensity ratio and the concentration of SO4(2-) ions. The quantitative equation
      for measur- ing the SO4(2-) concentration in aqueous solution at high temperature
      and high pressure is c(SO4(2-)) = 4.779 6(R + 1.469 x 10(-4)DeltaT + 1.340 x 10(
      4)DeltaP), where R is defined as the ratio of the SO4(2-) ions band intensity to
      the OH stretching single band intensity, T is the temperature relative to 23 
      degrees C, DeltaP is the pressure relative to 0.1 MPa, 23  degrees C <= T <= 390 
      degrees C, the concentration range of the SO4(2-) ions is 0.5-1.5 mol . L(-1),
      and the uncertainty of the equation is 6.5%. Raman spectroscopy can be used to
      measure the concentration of the Raman-active species in aqueous solutions.

PMID- 26197577
TI  - [Study on Raman Spectra of Some Animal and Plant Oils].
AB  - The spectral characteristics of different kinds of oil, either from plant seeds
      or animal fat, were studied with Raman spectroscopy. The experimental data were
      processed with the adaptive iteratively reweighted penalized least squares method
      to realize baseline correction, and provide evident information about their
      microscopic world. The spectra were analyzed and compared with each other in
      three parts: the Raman spectra comparison among different samples of plant oils,
      the analysis of the animal fat and the comparison between plant oils and the
      animal fat. The differences among the oils were observed in the analysis,
      including Raman shift and Raman intensity differences. This study not only yields
      the spectral basis for distinguishing or recognizing the different edible oils,
      but also confirms that Raman spectroscopy is an effective tool for identifying
      different oils.

PMID- 26197578
TI  - [Characterizing Structural Composition of Dissolved and Particulate Organic
      Matter from Sediment Pore Water in a Urban River Using Excitation-Emission Matrix
      Fluorescence with Self-Organizing Map].
AB  - Excitation-emission matrix (EEM) fluorescence with self-organizing map was
      applied to characterize structural composition and spatial distribution of
      dissolved (DOM) and particulate (POM) organic matter from sediment pore water in
      a typical urban river. Ten sediment pore water samples were collected from the
      mainstream of Baitabuhe River in Shenyang City of northeast China, along a human
      impact gradient, i. e. river source, rural and urban regions. DOM and POM were
      extracted from the pore water, and their EEM fluorescence spectra were measured.
      f450/500 of DOM ranged from 1.82 to 1.91, indicating that DOM is mainly from
      microbial source; f450/500 of POM ranged from 1.42 to 1.68, suggesting that POM
      derived from land. Four components were identified from DOM and POM fractions by
      self-organizing map, which included tyrosine-like, tryptophan-like, fulvic-like
      and humic-like matters. Tyrosine-like originated from fresh and less-degraded
      material with a high potential for oxida- tion, which was considered as
      representative components of DOM and POM. Tryptophan-like was associated with
      microbial byproduct-like material, and can indicate microbial activities. The
      abundance sum of all components in DOM is roughly 2 times more than that in POM.
      The mean relative abundance of tyrosine-like was more than 50%, while tryptophan
      like was about 18.6%-23.1%. Abundance of fulvic-like was much more than that of
      humic-like, but they were only a small proportion of organic matter fractions.
      Based on principal component analysis, the characteristics of DOM and POM
      distinctly were distributed along river source, rural region and urban region,
      proving that the river was deeply influenced by human activity.

PMID- 26197579
TI  - [Analysis of Samples from Wastewater Treatment Plant and Receiving Waters Using
      EEM Fluorescence Spectroscopy].
AB  - The samples from several treatment units in wastewater treatment plant (WWTP) and
      different sample sites of receiving waters were characterized using excitation
      emission matrix (EEM) fluorescence spectroscopy. After analyzed by parallel
      factor analysis (PARAFAC) method, the EEM fluorescence spectra of the principal
      components and fluorescence intensity scores matrix were acquired. Results showed
      that protein-like and fulvic-like substances were the main components of the
      samples from the WWTP and the receiving water body. The intensity of protein-like
      fluorescence in the influent samples was rather strong, and those of the
      following samples decreased significantly. The protein-like fluorescence
      intensity of the samples was relatively weak from the upstream of receiving water
      body, while those of the samples increased significantly from the water body near
      the urban area. The protein-like fluorescence intensity of upstream samples of
      the WWTP disposal outlet was stronger than that of downstream in the receiving
      waters. The fluorescence intensity scores of protein-like substance could be
      correlated with the COD concentration of the samples and the correlation curves
      were established. The correlation coefficient of the WWTP samples was 0. 930 and
      that of receiving water body samples was 0.913. The protein-like fluorescence
      could be used to evaluate the organic pollution of the samples. This study will
      provide a new method to investigate the operation status of WWTP and
      corresponding effect on the receiving water body.

PMID- 26197580
TI  - [Excitation-Emission Matrix Fluorescence Spectra Characteristics of DOM in
      Integrated Verical Flow Constructed Wetland for Treating Eutrophic Water].
AB  - Three-dimensional fluorescence parameters can reflect classification, properties
      and content change of pollutants in wastewater treatment. In the present paper,
      by using three-dimensional fluorescence characteristic analysis, comparative
      analysis of conventional organic pollutants such as COD, TN and TP, and three
      dimensional fluorescence spectrum analysis, the classification and content of
      dissolved organic pollutants were identified. We studied fluorescence spectra,
      fluorescence peak (R. U.), fluorescence index (FI), humification index (HIX) of
      DOM's four components in the entrance and effluent water and interstitial water,
      as well as the correlation between these four components and COD, TN and TP. The
      results showed that the position and intensity of the characteristic fluorescence
      peak center changed significantly before and after sewage treatment, indicating
      that the relative composition and content of the organic wastewater varied with
      wastewater treatment. Furthermore, the test results presented that humic-like
      composition was not degraded significantly, while protein-like composition was
      degraded significantly. And the protein-like component and COD, TN and TP
      presented significant positive correlation. This paper analyzed the fluorescence
      characteristics changes of dissolved organic matter in sewage treatment by using
      three-dimensional fluorescence spectrometry, and discussed the feasibility of
      three-dimensional fluorescence technique applied for description of dissolved
      organic pollutant degradation rule in the wastewater treatment process.

PMID- 26197581
TI  - [Fluorescence Resonance Energy Transfer Detection of Cobalt Ions by Silver
      Triangular Nanoplates and Rhodamine 6G].
AB  - In the present paper, the authors studied fluorescence resonance energy transfer
      (FRET) phenomenon between silver triangular nanoplates and bovine serum albumin
      (BSA)/Rhodamine 6G fluorescence complex, and established a fluorescence method
      for the detection of cobalt ions. We found that when increasing the silver
      triangular nanoplates added to certain concentrations of fluorescent bovine serum
      albumin (BSA)/Rhodamine 6G complex, the fluorescence of Rhodamine 6G would be
      quenched up to 80% due to the FRET between the quencher and donor. However, in
      the presence of cobalt ions, the disassociation of the fluorescent complex from
      silver triangular nanoplates occurred and the fluorescence of the Rhodamine 6G
      recovered. The recovery of fluorescence intensity rate (I/I0) has a good
      relationship with the cobalt ion concentration (cCO2+) added. Thus, the authors
      developed a fluorescence method for the detection of cobalt ions based on the
      FRET of silver triangular nanoplates and Rhodamine 6G.

PMID- 26197582
TI  - [Study on Therapeutic Effects of Ermiao Pill and Ermiao Pill Categorized Formula
      in Hyperuricemic Rats Using Spectroscopic Methods].
AB  - A stable mouse model of hyperuricemia was established by intraperitoneal
      injection of xanthine and oxonate, comparing the water extracts (containing crude
      drug 360 mg . mL(-1)) of Ermiao pill categorized formula (The ratio of
      atractylodes lancea to cortex phellodendri was 1:1, 1:2 and 2:1, respectively)
      and Ermiao pill (360 mg . mL(-1)) administered to different groups of animals
      continuously for two weeks and assessing the protection or treatment of drug on
      hyperuricemia. The xanthine oxidase (XOD) activities in serum and liver were
      detected by ultraviolet-visible spectroscopy at 570 nm wavelength, The results
      showed that as compared with each group, the XOD activity of the model group was
      significantly increased in serum (p < 0.01), XOD activity showed no significant
      difference in liver (p > 0.05), but compared with the model group, the XOD
      activity of each treatment group was significantly lower in serum and liver (p <
      0.01), especially for the group treated with Ermiao pill categorized formula with
      the ratio of Atractylodes lancea to Cortex Phellodendri being 1:2. The
      morphological changes of glomerular and tubular interstitial fibrosis were
      measured by Hematoxylin-eosin staining (HE staining) and Masson trichrome
      staining (Masson staining)for kidney paraffin sections. The results showed that
      the glomerular atrophy, vascular loops confusion, a certain degree of
      inflammatory cell infiltration, interstitial fibrosis and other phenomena
      appeared in the model group. Compared to model group, these pathological
      phenomena of the treatment groups were significantly improved. The area showed
      that compared with each group, the fibrosis of the model group was significantly
      increased (p < 0.01 or p < 0.05), but compared with Ermiao pill categorized
      formula, the differences for the group of Ermiao pill was lower (p < 0.01),
      especially for the group treated with Ermiao pill categorized formula with the
      ratio of Atractylodes lancea to Cortex Phellodendri being 1 : 2. In this
      experiment, the damage of kidney and XOD activity serve as the index to evaluate
      the protection or treatment of drug on hyperuricemia, providing a scientific
      basis for the development of Ermiao pill categorized formula.

PMID- 26197583
TI  - [Using UV-Vis Absorbance for Characterization of Maturity in Composting Process
      with Different Materials].
AB  - The present study was conducted to assess the degree of humification in DOM
      during composting using different raw materials, and their effect on maturity of
      compost based on UV-Vis spectra measurements and chemometrics method. The raw
      materials of composting studied included chicken manure, pig manure, kitchen
      waste, lawn waste, fruits and vegetables waste, straw waste, green waste, sludge,
      and municipal solid waste. During composting, the parameters of UV-Vis spectra of
      DOM, including SUVA254 , SUVA280 , E250/E365, E4/E6, E2/E4, E2/E6, E253/E203,
      E253/E220, A226-400, S275-295 and S350-400 were calculated, Statistical analysis
      indicated that all the parameter were significantly changed during composting.
      SUVA254 and SUVA280 of DOM were continuously increased, E250/E365 and E4/E6 were
      continuously decreased in DOM, while A226-400, S275-295 and S350-400 of DOM at
      the final stage were significantly different with those at other stages of
      composting. Correlation analysis indicated that the parameters were significantly
      correlated with each other except for E2/E4 and E235/E203. Furthermore, principal
      component analysis suggested that A226-400, SUVA254, S350-400, SUVA280 and
      S275~295 were reasonable parameters for assessing the compost maturity. To
      distinguish maturity degree among different composts, hierarchical cluster
      analysis, an integrated tool utilizing multiple UV-Vis parameters, was performed
      based on the data (A226-400, SUVA254, S350-400, SUVA280 and S275-295) of DOM
      derived from the final stage of composting. Composts from different sources were
      clustered into 2 groups. The first group included chicken manure, pig manure,
      lawn waste, fruits and vegetables waste, green waste, sludge, and municipal solid
      waste characterized by a lower maturity degree, and the second group contained
      straw waste and kitchen waste associated with a higher maturity degree. The above
      results suggest that a multi-index of UV-Vis spectra could accurately evaluate
      the compost maturity, and A226-400, SUVA254, S350-400, SUVA280 and S275-295 of
      DOM could serve as primary parameters when the compost maturity was assessed
      using UV-Vis spectra.

PMID- 26197584
TI  - [Mutual Effect on Determination of Gibberellins and Glyphosate in Groundwater by
      Spectrophotometry].
AB  - In the present study, a spectrophotometry method for the simultaneous
      determination of gibberellins (GA3) and glyphosate in groundwater was established
      and optimized. In addition, the mutual effect on simultaneous determination of
      GA3 and glyphosate was studied. Based on the experiment, good linearity (R2 >
      0.99) was obtained for GA3 in the range of 0-20 and 0-100 ug and for glyphosate
      in the range of 0-8 and 5-15 ug. The method's detection limit (MDL) of GA3 and
      glyphosate was 0.48 and 0.82 ug, respectively; and the recovery rates of 15 to
      150 ug GA3 and 3 to 10 ug glyphosate in all samples at a spiked level were 71.3%
      +/- 1.9% and 98.4% +/- 8.1%, respectively. No obvious influence of glyphosate (0
      100 mg . L(-1)) on the recovery rates of GA3 was observed, but the presence of
      glyphosate could cause slight determination precision decrease of GA3. Meanwhile,
      adding 2 mg . L(-1) GA3 can increase the recovery rate of glyphosate.

PMID- 26197585
TI  - [Trace Carbon Monoxide Detection with a Cavity Ring-Down Spectrometer].
AB  - A cavity ring-down spectrometer (CRDS) was built based on telecom distributed
      feedback (DFB) diode lasers. The ring down cavity was formed by mirrors of 99.
      997% reflectivity with a separation of 130 cm, with an empty ring down time of
      about 150 us. A minimum detectable absorption coefficient of 5 x 10(-12) cm(-1)
      was obtained by averaging about 1,000 recorded spectra. The ring down cavity is
      thermo-isolated, and used as an interferometer to calibrate the recorded
      spectrum. A feedback control scheme was applied to step scan the laser frequency,
      successively matching each of the longitudinal modes of the cavity. By measuring
      the CO contents in a standard gas sample, the quantitative capability of the CRDS
      instrument was demonstrated, and a CO detection limit of 4 ppb was achieved. The
      instrument was applied to monitor the CO concentration in ambient air.

PMID- 26197586
TI  - [Research on Accuracy and Stability of Inversing Vegetation Chlorophyll Content
      by Spectral Index Method].
AB  - Spectral index method was widely applied to the inversion of crop chlorophyll
      content. In the present study, PSR3500 spectrometer and SPAD-502 chlorophyll
      fluorometer were used to acquire the spectrum and relative chlorophyll content
      (SPAD value) of winter wheat leaves on May 2nd 2013 when it was at the jointing
      stage of winter wheat. Then the measured spectra were resampled to simulate TM
      multispectral data and Hyperion hyperspectral data respectively, using the
      Gaussian spectral response function. We chose four typical spectral indices
      including normalized difference vegetation index (NDVD, triangle vegetation index
      (TVI), the ratio of modified transformed chlorophyll absorption ratio index
      (MCARI) to optimized soil adjusted vegetation index (OSAVI) (MCARI/OSAVI) and
      vegetation index based on universal pattern decomposition (VIUPD), which were
      constructed with the feature bands sensitive to the vegetation chlorophyll. After
      calculating these spectral indices based on the resampling TM and Hyperion data,
      the regression equation between spectral indices and chlorophyll content was
      established. For TM, the result indicates that VIUPD has the best correlation
      with chlorophyll (R2 = 0.819 7) followed by NDVI (R2 = 0.791 8), while
      MCARI/OSAVI and TVI also show a good correlation with R2 higher than 0.5. For the
      simulated Hyperion data, VIUPD again ranks first with R2 = 0.817 1, followed by
      MCARI/OSAVI (R2 = 0.658 6), while NDVI and TVI show very low values with R2 less
      than 0.2. It was demonstrated that VIUPD has the best accuracy and stability to
      estimate chlorophyll of winter wheat whether using simulated TM data or Hyperion
      data, which reaffirms that VIUPD is comparatively sensor independent. The
      chlorophyll estimation accuracy and stability of MCARI/OSAVI also works well,
      partly because OSAVI could reduce the influence of backgrounds. Two broadband
      spectral indices NDVI and TVI are weak for the chlorophyll estimation of
      simulated Hyperion data mainly because of their dependence on few bands and the
      strong influence of atmosphere, solar altitude, viewing angle of sensor,
      background and so on. In conclusion, the stability and consistency of chlorophyll
      estimation is equally important to the estimation accuracy by spectral index
      method. VIUPD introduced in the study has the best performance to estimate winter
      wheat chlorophyll, which illustrates its potential ability in the area of
      estimating vegetation biochemical parameters.

PMID- 26197587
TI  - [Impact of Vegetation Structure on Drought Indices Based on MODIS Spectrum].
AB  - The drought indices based on MODIS spectral reflectance data are widely used for
      drought characterization and monitoring in agricultural context. Based on the
      PROSAIL model and MODIS observational data in Shandong in 2010, the present paper
      studied the impact of vegetation structure of leaf area index and physiological
      growth cycle on MODIS spectral drought index. The results showed that the
      reflectance of three MODIS bands in spectrum of near-infrared and shortwave
      infrared changes significantly with leaf water content of vegetation. Therefore,
      the five kinds of MODIS spectral drought index constructed by those MODIS bands
      can be used to monitor the leaf water content of vegetation. However, all drought
      indices are affected by leaf area index. In general, the impact is serious in the
      case of low LAI values and is weakened with the increase in LAI value. The study
      found that physiological vegetation growth cycle also affects the magnitude of
      MODIS spectral drought indices. In conclusion, the impact of vegetation structure
      must be carefully considered when using MODIS spectral drought indices to monitor
      drought. The conclusion of this study provides a theoretical basis for remote
      sensing of drought monitoring.

PMID- 26197588
TI  - [Study on the Reliability Assessment Method of Heavy Vehicle Gearbox Based on
      Spectrometric Analysis].
AB  - Spectrometric oil analysis is of great importance for wear condition monitoring
      of gearbox. In this context, the contents of main elements compositions in the
      bench test of heavy vehicle gearbox are obtained by atomic emission spectrometric
      oil analysis first. Then correlation analysis of the test data and wearing
      mechanism analysis are carried out to get the metal element which could be used
      to describe the wearing and failure of the gearbox. The spectrometric data after
      filling/changing oil are corrected, and the laws of the contents of main elements
      compositions during tests are expressed as linear functions. After that, the
      reliability assessment is executed with considering the degradation law and
      discreteness of test data, in which the mean and standard deviation of normal
      distribution of spectrometric oil data at each time point are adopted. Finally,
      the influences of the threshold are discussed. It has been proved that the
      contents of metal element Cu, which is got by spectrometric oil analysis of
      different samples, could be used to assess the reliability of heavy vehicle
      gearbox. The reason is that the metal element Cu is closely related to the
      general wear state of gearbox, and is easy to be measured. When the threshold of
      Cu content is treated as a constant, bigger threshold means higher reliability at
      the same time, and the mean value of threshold has significant impact on the
      reliability assessment results as R > 0.9. When the threshold is treated as a
      random variable, bigger dispersion of threshold means smaller slope of
      reliability against time, and also means lower reliability of gearbox as R > 0.9
      at the same time. In this study, the spectrometric oil analysis and probability
      statistics are used together for the reliability assessment of gear box, which
      extends the application range of spectrometric analysis.

PMID- 26197589
TI  - [Multi-Target Recognition of Internal and External Defects of Potato by Semi
      Transmission Hyperspectral Imaging and Manifold Learning Algorithm].
AB  - The present paper put forward a non-destructive detection method which combines
      semi-transmission hyperspectral imaging technology with manifold learning
      dimension reduction algorithm and least squares support vector machine (LSSVM) to
      recognize internal and external defects in potatoes simultaneously. Three hundred
      fifteen potatoes were bought in farmers market as research object, and semi
      transmission hyperspectral image acquisition system was constructed to acquire
      the hyperspectral images of normal external defects (bud and green rind) and
      internal defect (hollow heart) potatoes. In order to conform to the actual
      production, defect part is randomly put right, side and back to the acquisition
      probe when the hyperspectral images of external defects potatoes are acquired.
      The average spectrums (390-1,040 nm) were extracted from the region of interests
      for spectral preprocessing. Then three kinds of manifold learning algorithm were
      respectively utilized to reduce the dimension of spectrum data, including
      supervised locally linear embedding (SLLE), locally linear embedding (LLE) and
      isometric mapping (ISOMAP), the low-dimensional data gotten by manifold learning
      algorithms is used as model input, Error Correcting Output Code (ECOC) and LSSVM
      were combined to develop the multi-target classification model. By comparing and
      analyzing results of the three models, we concluded that SLLE is the optimal
      manifold learning dimension reduction algorithm, and the SLLE-LSSVM model is
      determined to get the best recognition rate for recognizing internal and external
      defects potatoes. For test set data, the single recognition rate of normal, bud,
      green rind and hollow heart potato reached 96.83%, 86.96%, 86.96% and 95%
      respectively, and he hybrid recognition rate was 93.02%. The results indicate
      that combining the semi-transmission hyperspectral imaging technology with SLLE
      LSSVM is a feasible qualitative analytical method which can simultaneously
      recognize the internal and external defects potatoes and also provide technical
      reference for rapid on-line non-destructive detecting of the internal and
      external defects potatoes.

PMID- 26197590
TI  - [Detection of Carbon Dioxide Concentration in Soil Profile Based on Nondispersive
      Infrared Spectroscopy Technique].
AB  - In order to explore the variation of CO2 concentration and soil respiration in
      soil profile, the nondispersive infrared (NDIR) spectroscopy technique was
      applied to continually estimate the soil CO2 concentration in different soil
      layers (the humus horizon, A-, B-, C-horizon) in situ. The main instrument used
      in this experiment was silicon-based nondispersive infrared sensor, which could
      work in severe environment. We collected the Measurement value by NDIR
      spectroscopy technique throughout 2013. The values of soil carbon flux in
      different soil layers were calculated based on the model of gradient method and
      calibrated by measuring with an automated soil CO2 efflux system (LI-8100). The
      results showed that: a vertical gradient for the carbon dioxide concentration in
      soil profile was found, and the concentration was highest in the deepest soil
      horizon. Moreover, A linear correlation between the soil CO2 effluxes was
      calculated based on model and measurement, and the model prediction correlation
      coefficient was 0.9069, 0.7185, 0.8382, and 0.9030 in the H-, A-, B-, and C
      horizon, respectively. The roots of mean square error (RMSE) were 0.2067, 0.1041,
      0.0156, and 0.0096 in the H-, A-, B-, and C-horizon, respectively. These results
      suggest that the gradient method based on the NDIR spectroscopy technique can be
      successfully used to measure soil CO2 efflux in different soil layers, which
      reveal that diffusion and convection transport CO2 between the soil layers. It is
      a promising sensor for detecting CO2 concentration in soil profile, providing the
      basic data for calculating the global carbon in soil profile.

PMID- 26197591
TI  - [Three-Iindex-Value Method for Rapid Screening Unqualified Vegetable Oil].
AB  - In the present study, by measuring the A3 005 (representing unsaturation), A985
      (representing conjugated fatty acids), A960 + A985 (representing trans-fatty acid
      ) of southern common vegetable oils (peanut oil, corn oil, canola oil, soybean
      oil, sunflower oil, tea seed oil and olive oil), "waste oil" and overdue
      vegetable oils, the pass-setting-range of these three index values for the
      vegetable oils was obtained. On this basis, a method for rapid screening
      unqualified vegetable oil (expired, adding low-cost oil, adding "waste oil") was
      established. The method effectively improved the monitoring efficiency of
      vegetable oil. With this method of screening a number of suspected substandard
      oils were proved unqualified by determination of fatty acid composition and 11,
      12, 13, 17 fatty acid content. Through the combination of several detection
      methods, the causes for disqualification of vegetable oils can be further
      inferred.

PMID- 26197592
TI  - [Biosorption of Radionuclide Uranium by Deinococcus radiodurans].
AB  - As a biological adsorbent, Living Deinococcus radiodurans was used for removing
      radionuclide uranium in the aqueous solution. The effect factors on biosorption
      of radionuclide uranium were researched in the present paper, including solution
      pH values and initial uranium concentration. Meanwhile, the biosorption mechanism
      was researched by the method of FTIR and SEM/EDS. The results show that the
      optimum conditions for biosorption are as follows: pH = 5, co = 100 mg . L(-1)
      and the maximum biosorption capacity is up to 240 mgU . g(-1). According to the
      SEM results and EDXS analysis, it is indicated that the cell surface is attached
      by lots of sheet uranium crystals, and the main biosorpiton way of uranium is the
      ion exchange or surface complexation. Comparing FTIR spectra and FTIR fitting
      spectra before and after biosorption, we can find that the whole spectra has a
      certain change, particularly active groups (such as amide groups of the protein,
      hydroxy, carboxyl and phosphate group) are involved in the biosorption process.
      Then, there is a new peak at 906 cm(-1) and it is a stretching vibration peak of
      UO2(2+). Obviously, it is possible that as an anti radiation microorganism,
      Deinococcus radiodurans could be used for removing radionuclide uranium in
      radiation environment.

PMID- 26197593
TI  - [Retrieving Chromophoric Dissolved Organic Matter in Guanting Reservoir Based on
      in-situ Measured Reflectance Data].
AB  - In the present paper, Guanting Reservoir located in Zhangjiakou City, Hebei
      province and Yanqing District, Beijing, was selected as the study area, and
      Chromophoric dissolved organic matter (CDOM) content (represented by the CDOM
      absorption coefficient at 440 nm, aCDOM (440)) was inverted through semi
      analytical method and empirical method. The data used in this paper include the
      spectral data (R (lambda)) collected on October 26, 2013 over Guanting Reservoir
      and aCDOM (lambda) measured in the laboratory. A semi-analytical method (QAA
      CDOM) was validated and improved accordingly. The inversion result accuracy of
      QAA-CDOM was not bad, the root-mean-square error (RMSE) was 0.10 and the mean
      relative error (sigma) was 10.8%. The QAA-CDOM method was improved by
      recalculating the value of Q (the ratio of upwelling irradiance to upwelling
      radiance just below the water surface) by the field spectral data to replace the
      fixed value. After this improvement, the inversion accuracy was slightly
      improved, with RMSE of 0.09 and sigma of 10.2%. After that, four band ratios were
      used in linear regression with aCDOM (440) to build empirical inversion models.
      The results showed that the performance of the model based on Rrs (531)/Rrs (551)
      was the best, with R2 of 0.63. The RMSE and sigma of the aCDOM(440) result
      inverted by the empirical method were 0.08 and 8.8% respectively. The empirical
      method was of higher precision than that of the semi-analytical method, but the
      bands and coeffi- cients used in the empirical method need to be calibrated by
      concurrently measured data in each study area. On the contrary, semi-analytical
      method does not need calibration, and is easier to be applied.

PMID- 26197594
TI  - [Determination of Soluble Solid Content in Strawberry Using Hyperspectral Imaging
      Combined with Feature Extraction Methods].
AB  - Hyperspectral imaging combined with feature extraction methods were applied to
      determine soluble sugar content (SSC) in mature and scatheless strawberry.
      Hyperspectral images of 154 strawberries covering the spectral range of 874-1,734
      nm were captured and the spectral data were extracted from the hyperspectral
      images, and the spectra of 941~1,612 nm were preprocessed by moving average (MA).
      Nineteen samples were defined as outliers by the residual method, and the
      remaining 135 samples were divided into the calibration set (n = 90) and the
      prediction set (n = 45). Successive projections algorithm (SPA), genetic
      algorithm partial least squares (GAPLS) combined with SPA, weighted regression
      coefficient (Bw) and competitive adaptive reweighted sampling (CARS) were applied
      to select 14, 17, 24 and 25 effective wavelengths, respectively. Principal
      component analysis (PCA) and wavelet transform (WT) were applied to extract
      feature information with 20 and 58 features, respectively. PLS models were built
      based on the full spectra, the effective wavelengths and the features,
      respectively. All PLS models obtained good results. PLS models using full-spectra
      and features extracted by WT obtained the best results with correlation
      coefficient of calibration (r(c)) and correlation coefficient of prediction
      (r(p)) over 0.9. The overall results indicated that hyperspectral imaging
      combined with feature extraction methods could be used for detection of SSC in
      strawberry.

PMID- 26197595
TI  - [Research on Oil Sands Spectral Characteristics and Oil Content by Remote Sensing
      Estimation].
AB  - Visible and near infrared spectroscopy is a proven technology to be widely used
      in identification and exploration of hydrocarbon energy sources with high
      spectral resolution for detail diagnostic absorption characteristics of
      hydrocarbon groups. The most prominent regions for hydrocarbon absorption bands
      are 1,740-1,780, 2,300-2,340 and 2,340-2,360 nm by the reflectance of oil sands
      samples. These spectral ranges are dominated by various C-H overlapping overtones
      and combination bands. Meanwhile, there is relatively weak even or no absorption
      characteristics in the region from 1,700 to 1,730 nm in the spectra of oil sands
      samples with low bitumen content. With the increase in oil content, in the
      spectral range of 1,700-1,730 nm the obvious hydrocarbon absorption begins to
      appear. The bitumen content is the critical parameter for oil sands reserves
      estimation. The absorption depth was used to depict the response intensity of the
      absorption bands controlled by first-order overtones and combinations of the
      various C-H stretching and bending fundamentals. According to the Pearson and
      partial correlation relationships of oil content and absorption depth dominated
      by hydrocarbon groups in 1,740-1,780, 2,300-2,340 and 2,340-2,360 nm wavelength
      range, the scheme of association mode was established between the intensity of
      spectral response and bitumen content, and then unary linear regression(ULR) and
      partial least squares regression (PLSR) methods were employed to model the
      equation between absorption depth attributed to various C-H bond and bitumen
      content. There were two calibration equations in which ULR method was employed to
      model the relationship between absorption depth near 2,350 nm region and bitumen
      content and PLSR method was developed to model the relationship between
      absorption depth of 1,758, 2,310, 2,350 nm regions and oil content. It turned out
      that the calibration models had good predictive ability and high robustness and
      they could provide the scientific basis for rapid estimation of oil content in
      oil sands in future.

PMID- 26197596
TI  - [Research Progress in Analytical Technology for Heavy Metals in Atmospheric
      Particles].
AB  - Atmospheric particles have become the primary atmospheric pollutions, of which
      the heavy metals, owing to non-degradability and hysteresis, a serious threat to
      human life and natural environment, have become a hot research issue currently.
      The analytical methods of heavy metals in atmospheric particles are summarized in
      the present review, including atomic absorption spectrometry, inductively coupled
      plasma atomic emission spectrometry, inductively coupled plasma mass
      spectrometry, neutron activation analysis, fluorescence spectrometry, glow
      discharge atomic emission spectrometry, microwave plasma atomic emission
      spectrometry, and laser induced breakdown spectroscopy, and some proposals are
      tried to make for improving the shortcomings of these technologies: continuum
      source Atomic absorption spectrometry for simultaneously measuring multi
      elements, atomic emission spectrometry for direct determination of particulates,
      high resolution laser ablation inductively coupled plasma mass spectrometry for
      determination of solid samples, low scattering synchrotron fluorescence spectrum
      for determination of atmospheric particulate matter and k0 neutron activation
      analysis for determination of radioactive elements in the troposphere Analysis
      techniques of heavy metals in atmospheric particulate matter are promoted to
      develop toward being real-time, fast, low- detection-limit, direct-measurement
      and simple-operation due to the spatial and temporal distribution difference of
      the heavy metals in atmospheric particles and human requirement for improvement
      of ambient air quality as well as rapid development of modern instrument science
      and technology.

PMID- 26197597
TI  - [Influence of Flame Emission Spectroscopy on K measurement Using Laser Induced
      Breakdown Spectroscopy].
AB  - During the combustion of coal or biomass, the inherent alkali metals in the fuel
      will be released to the gas phase. The released alkali species condensed during
      the cooling of the flue gas, which may subsequently cause problems with ash
      deposition and corrosion in thermal fuel conversion systems. Laser Induced
      Breakdown Spectroscopy (LIBS) is an effective technique to measure the alkali
      species in the plume of burning coal or biomass. In this study, an LIBS
      experimental system with a flat flame burner was set up, and the Flame Emission
      Spectroscopy (FES) and LIBS of K in the flat flame environment were measured
      using different ICCD gate-width times. The experimental results revealed that
      with the same ICCD gate-width time, the LIBS intensity of K was higher than the
      FES intensity of K in the flat flame. With the increase of the ICCD gate-width
      time, both intensities increased, but their increase rates were different: the
      increase rate of the LIBS intensity of K was firstly fast then became slow, but
      the increase rate of the FES intensity of K was constant. Furthermore, the
      intensity ratio of LIBS to FES of K increased monotonically with the ICCD gate
      width time in the range of 0-8 us, until reaching approximately 4. Then, further
      increasing the ICCD gate-width time, such ratio decreased slowly with an
      asymptote value of 1. After analyzing the influences of the FES on the LIBS
      measurement of K in a flame condition, it is proposed that to minimize such
      influence, the optimization of the ICCD gate-width time was necessary, which
      maximized the intensity ratio of LIBS to FES-of K and facilitated the measurement
      accuracy of K in the flame environment using LIBS.

PMID- 26197598
TI  - [Study on Content Determination of Lead and Arsenic in Four Traditional Tibetan
      Medicine Prescription Preparations by Wet Digestion Flow Injection-Hydride
      Generation-Atomic Absorption Spectrometry].
AB  - Four common traditional tibetan medicine prescription preparations
      "Anzhijinghuasan, Dangzuo, Renqingchangjue and Rannasangpei" in tibetan areas
      were selected as study objects in the present study. The purpose was to try to
      establish a kind of wet digestion and flow injection-hydride generation-atomic
      absorption spectrometry (FI-HAAS) associated analysis method for the content
      determinations of lead and arsenic in traditional tibetan medicine under
      optimized digestion and measurement conditions and determine their contents
      accurately. Under these optimum operating conditions, experimental results were
      as follows. The detection limits for lead and arsenic were 0.067 and 0.012 ug .
      mL(-1) respectively. The quantification limits for lead and arsenic were 0.22 and
      0.041 ug . mL(-1) respectively. The linear ranges for lead and arsenic were 25
      1,600 ng . mL(-1) (r = 0.9995) and 12.5-800 ng . mL(-1) (r = 0.9994)
      respectively. The degrees of precision(RSD) for lead and arsenic were 2.0% and
      3.2% respectively. The recovery rates for lead and arsenic were 98.00%-99.98% and
      96.67%-99.87% respectively. The content determination results of lead and arsenic
      in four traditional tibetan medicine prescription preparations were as fol- lows.
      The contents of lead and arsenic in Anzhijinghuasan are 0.63-0.67 ug . g(-1) and
      0.32-0.33 ug . g(-1) in Anzhijinghua- san, 42.92-43.36 ug . g(-1) and 24.67-25.87
      ug . g(-1) in Dangzuo, 1,611. 39-1,631.36 ug . g(-1) and 926.76-956.52 ug- g(-1)
      in Renqing Changjue, and 1,102.28-1,119.127 ug-g(-1) and 509.96-516.87 ug . g(-1)
      in Rannasangpei, respectively. This study established a method for content
      determination of lead and arsenic in traditional tibetan medicine, and determined
      the content levels of lead and arsenic in four tibetan medicine-prescription
      preparations accurately. In addition, these results also provide the basis for
      the safe and effective use of those medicines in clinic.

PMID- 26197599
TI  - [Determination of Arsenic in Food Package Aluminum by Ultrasound Assisted Solid
      Phase Extraction/ICP-AES].
AB  - Determination of arsenic in pure aluminum by inductively coupled plasma atomic
      emission spectrometry was interfered by aluminum matrix. The experiment showed
      that when the mass concentration of Al was greater than or equal to 5 000 times
      the As in the test solution, the measurement error was greater than 5%. In order
      to eliminate the interference, strong acid cation exchange fiber (SACEF) was used
      as solid phase extraction agent to adsorb Al(3+). The extraction conditions
      included amount of SACEF, extraction time, temperature and pH were investigated.
      The optimal extraction conditions were that 0.9000 g SACEF was used to extract
      the aluminum from the sample solution of pH 2.0 at 55  degrees C for 5 min with
      the ultrasonic assist, and in this case, the arsenic in the form of arsenic acid
      was not extracted and left in the solution for the determination. The results
      showed that after treating 10. 00 mL test solution containing 1.00 ug arsenic and
      20.0 mg aluminum, arsenic did not lose. The mass concentration of residual
      aluminum in the raffinate was about 2,000 times the As, which had not interfered
      the determination of arsenic. The detection limit (3 s) was 0.027 ug . mL(-1) and
      quantification limit (10 s) was 0.0091 ug . mL(-1). The proposed method was
      successfully applied to the separation and determination of arsenic in the
      synthetic samples, the aluminum cans and the barbecue aluminum foil. Recovery was
      in the range of 98.3%-105% and RSD (n = 3) was in the range of 0.1%-4.3%. The
      results showed that the content of arsenic in the aluminum cans and the aluminum
      barbecue foil was below the limited value of national standard (GB/T 3190-2008).

PMID- 26197600
TI  - [Determination of Trace Germanium in Plant Samples by Dry Ashing-Atomic
      Fluorescence Spectrometry].
AB  - To reduce the limit of detection (LOD) and allow the accurate determination of
      Ge, a dry ashing method was performed to enrich the Ge in plant samples. A method
      for the determination.of trace Ge in plant samples by HG-AFS was established.
      Study of the effect of temperature on the ashing of plant samples showed that no
      volatile loss of Ge occurred even at 900  degrees C. Additional experiments
      indicated that a 4 h burning process at 600  degrees C would be sufficient to
      fully ash the plant samples. Various digestion methods (involving nitric acid,
      hydrofluoric acid, and sulfuric acid digestion methods) for ashed samples were
      investigated. High-temperature ashing with large sample weights was used, which
      could reduce the reagent doses and the method's LOD effectively and
      simultaneously, the precision of the method was improved. The method's LOD was
      0.27 ng . g(-1), and the relative standard deviation was 3.99%-6.81%. Verified
      with national biological reference materials (grade I), the proposed method was
      accurate and reliable.

PMID- 26197601
TI  - [Determination of Mineral Elements in Choerospondias Axillaris and Its
      Extractives by ICP-AES].
AB  - Nine elements in Choerospondias axillaris flesh, peels, aqueous extractives and
      gastric digesta were determined by the inductively coupled plasma atomic emission
      spectrometry (ICP-AES) in the present study. The results showed that the contents
      of Fe, Ca, Zn, Mn, Al, Mg, Cu, K and P in the flesh were 27.37, 269.88, 1.51,
      2.45, 1.95, 195.30, 2.45, 2,970.11, and 133.94 ug . g(-1), respectively. They are
      lower than that in the peels, about 40.31%, 11.70%, 21.68%, 4.27%, 10.58%,
      15.76%, 68.72%, 42.04%, and 22.59%, respectively. For microwave assistant
      extraction, the release rate of Mn was highest (81.68%), while Fe was lowest
      (4.42%) in the flesh. The release rate of Zn was the highest (79.00%), while that
      of A1 was the lowest (4.94%) in the peels. Except Fe, Cu and Zn, the release
      rates of the other elements in flesh were higher than those in the peels. After
      gastric digestion, the release rates of nine elements were 3.25%-87.51% in the
      flesh and 7.11%-50.69% in the peels. The release rates of minerals in the flesh
      were found to be higher than those in the peels except Fe and Cu. Microwave
      assistant extraction can more efficiently release Fe, Ca, Mn, Mg and K from the
      flesh than the gastric digestion do. While gastric digestion had a significant
      effect on the peels, the release rates of elements, except Zn, were higher than
      those in microwave assistant extraction. Therefore, the difference of
      distribution and release of mineral elements between peels and flesh of
      Choerospondias axillaris was understood, which will provide a positive guide for
      further study of bioavailability of minerals for human body.

PMID- 26197602
TI  - [Identification of Chinese Traditional Medicine Cistanches Herba from Different
      Places by HPLC-ESI-MS and FTIR Methods].
AB  - Five samples of Cistanches Herba from different places were analyzed by HPLC-ESI
      MS and FTIR methods. The effective compositions in Cistanches Herba including
      cistanoside A, echinacoside, acteoside , isoacteoside, 2'-actylacteoside,
      cistanoside C and tubluoside B were determined by HPLC-MS. The common peak ratio
      and variant peak ratio were calculated by FTIR spectroscopy of the five samples
      and the dual index sequence of common peak ratio and variant peak ratio were
      established. The results showed that the evaluation results of the samples by the
      two methods were the same. The general fake plant Cynomorii Herba could be
      identified by FTIR. HPLC-ESI-MS, which has high sensitivity and rapid
      determination procedure, can be used to evaluate quality of Cistanches Herba by
      quantitative analysis of the primary compositions. FTIR is a non-destructive
      analysis method. without complicated extraction and separation procedures to the
      samples. The absorption strength and the absorption shape were the synergistic
      effect of the functional groups and the nestification of the components in
      Cistanches Herba. The provided method has some advantages such as rapid analysis
      process, good reproducibility, non-destructive, small quantity of sample, simple
      treatment, good specificity, low-cost and environment-friendly. The method meets
      the trend of complex analysis and whole analysis for the Chinese medicines.
      Combination of FTIR and HPLC-ESI-MS was a good method for identification and
      evaluation of quality of Chinese medicines.

PMID- 26197603
TI  - [Study on Speciation Analysis and Ecological Risk Assessment of Heavy Metals in
      Surface Sediments in Gansu, Ningxia and Inner Mongolia Sections of the Yellow
      River in Wet Season with HR-ICP-MS].
AB  - In order to continuously study the contents, pollution condition and potential
      ecological risk of heavy metals in surface sediments in Gansu, Ningxia and Inner
      Mongolia sections of the Yellow River in wet seasons in different years, the
      speciation analysis of 9 kinds of heavy metals including Cd, Pb, Cr, Ni, Cu, V,
      Co, Zn and Mn, pollution condition and potential ecological risk of heavy metals
      in surface sediments from 10 sampling sites like Baotoufuqiao (S2),
      Shizuishantaolezhen (S6) and Wujinxia (S9) in Gansu, Ningxia and Inner Mongolia
      sections of the Yellow River in 2012 wet season were studied with BCR sequential
      extraction and high resolution inductively coupled plasma-mass spectrometry (HR
      ICP-MS) based on our previous works. The results implied that the order of heavy
      metals average contents in the 10 sediment samples were the same: Mn>V>
      Zn>Cr>Cu>Ni>Pb>Co>Cd. In the sediments, heavy metals mainly existed in the form
      of residual fraction, which indicated that the bioavailability or environmental
      impact was low. Results of geo-accumulation indices (Igeo) showed that Igeo(CD),
      was the largest among the heavy metals with the strongest pollution, while
      IGEO(Mn)was the smallest. Enrichment factor (EF) indicated that only Cd and Cu
      were enriched at some sampling sites. In S5, because EFcd reached 4. 69, Cd was
      affected by human activities obviously and the result was consistent with I.
      Potential ecological risk index (RI) implied that the RI values in S1, S2 and S5
      were between 150 and 300, which belonged to moderate polluting degree, while
      others were less than 150, belonging to light pollution degree. The results of
      this paper could not only provide reliable experimental data and theoretical
      basis for the relevant departments, but also supply the technical support for
      constructing mathematics model of sediments-pollutants transport, systematically
      researching the migration and transformation rule of persistent toxic substances
      and environmental assessment in these reaches.

PMID- 26197604
TI  - [Research on Test Method of Metallic Element Contained in Tea Based on EDXRF
      Technique].
AB  - As it has been certified by experimental testing that when using the energy
      dispersive X-ray fluorescence (EDXRF) method to analyze the metallic elements
      contained in the tea the energy segment of effective X-ray fluorescence photons
      is located between 3 and 16 keV. Accordingly the spectral correction element is
      targeted at the copper elements located near the energy center(8 keV). The copper
      elements are also used as the picketage to be the standard curve. In the energy
      segment of effective X-ray fluorescence photons contained in the tea 1.25 mg .
      kg(-1) of the average detection limit was obtained by using the spiked method to
      analyze four elements of copper, iron, zinc and lead. Compared with the flame
      atomic absorption spectrum(FAAS), the actual relative error of the tested value
      by EDXRF is less than 6%, and the relative standard deviation is less than 5%.
      The result by T test shows that p > 0.05. The conclusions are that there are no
      statistically significant differences between EDXRF and FAAS. The measured
      results gained by the two methods agree with each other. And EDXRF can be used
      thoroughly to test the metal contents contained in the tea. The result shows that
      it is feasible to test the metallic contents contained in the tea by EDXRF, and
      its measured result can meet the requirements of field testing and analysis.

PMID- 26197605
TI  - [Preparation and Performance of Ultrafast gamma-CuI Scintillation Conversion
      Screen].
AB  - Micro-columnar structured gamma-CuI scintillation conversion screen with columnar
      diameter in the micrometer and thickness about 17 um were prepared by thermal
      evaporation method on quartz substrates with different temperatures. X-ray
      excited luminescence spectra of the screens show two peaks located at 430 nm and
      near 700 nm, which correspond to the fast and slow emission components,
      respectively. The fast one dominated. The intensity of 430 nm peak decreased as
      the substrate temperature rose from 170  degrees C to 210  degrees C. At the same
      time the intensity of 700 nm band increased. The changes may be attributed to the
      iodine loss from screen caused by the substrate temperature. The phenomenon of
      iodine loss was observed by the Rutherford backscattering experiment. The crystal
      structure of the screens presents (111) preferred orientation, which is
      independent of the substrate temperature. As the temperature rose to 210  degrees
      C, two weak additional peaks of (220) and (420) gamma-CuI crystal planes in X-ray
      diffraction patterns appeared due to the increase in kinetic energy of CuI
      molecules. The scanning electron microscopy images of the screens showed that the
      columnar structure was improved when the substrate temperature increased from 170
      degrees C to 190  degrees C, but it would be degenerated when the temperature
      continued to rise to 210  degrees C because of the surface and bulk diffusion
      effects of the depositing molecules. Finally, the spatial resolution of the gamma
      CuI scintillation screens was measured by knife-edge method, and they are 4.5,
      7.2 and 5.6lp . mm(-1) for the screens prepared at the substrates temperatures of
      170, 190 and 210  degrees C, respectively. The result shows that micro-column
      structure could improve the spatial resolution of gamma-CuI scintillation screen.

PMID- 26197606
TI  - [The Influence of Oxygen Incorporation on the Microstructure and Band Gap
      Properties of the nc-Si Films].
AB  - The authors prepared nc-SiOx: H thin films using plasma enhanced chemical vapor
      deposition methods (PECVD) and investigated the influence of oxygen incorporation
      on the microstructure and band gap properties of the films. The results indicated
      that with the increase in oxygen mixing ratio (CO2/SiH4), the grain size of the
      nanocrystal-silicon grain as well as the crystallinity of the film reduced, and
      the surface tensile stress of the nanocrystal-silicon grain first increased and
      then decreased. Fourier infrared absorption spectra analysis indicated that, with
      the increase in oxygen mixing ratio, the intensity of the oxygen rich Si--O bond
      increased while that of the silicon rich Si--O bond decreased and the structure
      factor reduced in the meantime accompanied by the improved order degree of thin
      films. The structure factor increased when the oxygen mixing ratio exceeded 0.08,
      which shows that the order degree of thin films dropped. In addition, the optical
      gap increased and the band tail width first increased and then decreased as a
      result of the incorporation of the oxygen. As a result, the microstructure and
      band gap properties of the films can be controlled by incorporating oxygen. And
      the crystallinity and optical gap of the material was high, and the
      microstructure of the films was improved at the same time when the oxygen mixing
      ratio was 0. 08, so it can be used as intrinsic layer of the thin-film solar
      cells.

PMID- 26197607
TI  - [Study on the Interface Characteristics of Cemented Carbide after Stripping Ti
      Department Coatings].
AB  - TiAlN Coatings were stripped by chemical method, which were deposited on Y WZ
      Alloy by arc ion plating. The surface morphology and composition of the cemented
      carbide after stripping TiAlN coatings by chemistry method were analyzed. It was
      found that TiA1N coatings on the cemented carbide substrates could be removed by
      being taken in 30% of hydrogen peroxide and potassium oxalate in alkaline mixed
      solution (V(NaOH so1ution):V(3O%H2O2):V(COOK solution) = 1:1:1) at 45  degrees C
      for 45 minutes. The surface of the cemented carbide substrate was bright, and the
      color was the same as that before depositing TiA1N coatings. The surface of the
      substrate after removing was studied by X-ray photoelectron spectrum (XPS). The
      results showed that binding energies of the W element and the main peak of N
      element on the substrate surface were much close to the criterion binding energy
      in the XPS data-base; and the valence of the element on the YW2 alloy changed
      little. The Al, Ti and N elements diffusing into the superficial zone of the
      sample during the coating depositing process made their contents increase and the
      band energy location offset after stripping the coating. TiN and A1N were formed,
      which benefit to increase the film-substrate cohesion during re-preparing
      coatings. The influence of stripping solution on the corrosion degree of cemented
      carbide substrate was small.

PMID- 26197608
TI  - Effect of Heat Treatment Temperature on the Spectral Properties of Cu-Ni Coating.
AB  - Cu-Ni coatings were prepared on the surface of nickel by electrodeposition
      method, and Cu-Ni coatings were heat-treated in 25-900  degrees C. Heat-treated
      Cu-Ni coatings were characterized with scanning electron microscopy (SEM), energy
      dispersive x-ray analysis (EDAX) and X-ray diffraction (XRD) techniques,
      respectively. Effects of heat treatment temperature on the spectral properties of
      Cu-Ni coatings were studied. The surface of Cu-Ni coating is composed of the
      nodules. The nodules of Cu-Ni coating surface become smaller with the increase in
      heat treatment temperature in 25-600  degrees C. The nodules of Cu-Ni coating
      surface become smaller and the dividing line between the nodules becomes more
      blurred with the increase in heat treatment temperature in 600-900  degrees C.
      The contents of copper in Cu-Ni coating decrease from 82.52 at % to 78.30 at %
      with the increase in heat treatment temperature in the range of 25-900  degrees
      C; the contents of nickel in Cu-Ni coating increase from 17.48 at % to 21.70 at %
      with the increase in heat treatment temperature in the range of 25-900  degrees
      C. The crystal structure of Cu-Ni coating is Cu0:8lNi0.19 cubic crystal
      structure. The crystal structure of the CuO0.81Ni0.19 becomes more complete with
      the increase in heat treatment temperature in 25- 300  degrees C. Part of crystal
      structure of the Cu0.81AlNi0.19 can turn Cu0.8lNi0.19 cubic crystal structure
      into Cu3.8Ni cubic crystal structure, and is advantageous to Cu3.8Ni (311) and
      Cu0.81Ni0.19 (311) growth with the increase in heat treatment temperature in 600
      900  degrees C.

PMID- 26197609
TI  - [Correction of Fiber Throughput Variation Due to the Focal Ratio Degradation].
AB  - The focal ratio degradation (FRD) of optical fiber is one of major sources
      causing light loss in multi-fiber astronomical instruments. Meanwhile, the sky
      subtraction is crucial to multi-fiber spectra reduction, especially for the
      objects which are as faint as the sky background, not to mention for those even
      fainter ones. To improve the accuracy of sky subtraction, it is necessary to
      normalize the throughput among object fibers and sky sampling fibers. The
      rotation and twist during mounting and rotating could change the FRD of
      individual fibers, which means the variation of the transmission throughput among
      fibers. We investigate such throughput variation among LAMOST fibers and its
      correlation with the intensity of sky emission lines on all wavelength coverage
      in this paper. On the basis of this work, we present an approach to correcting
      the varied fiber throughput by measuring the intensity of the sky emission lines
      as the secondary throughput correction. This approach has been applied to LAMOST
      2D Pipeline.

PMID- 26197610
TI  - [Spectra Classification Based on Local Mean-Based K-Nearest Centroid Neighbor
      Method].
AB  - In the present paper, a local mean-based K-nearest centroid neighbor (LMKNCN)
      technique is used for the classification of stars, galaxies and quasars (QSOS).
      The main idea of LMKNCN is that it depends on the principle of the nearest
      centroid neighborhood(NCN), and selects K centroid neighbors of each class as
      training samples and then classifies a query pattern into the class with the
      distance of the local centroid mean vector to the samples . In this paper, KNN,
      KNCN and LMKNCN were experimentally compared with these three different kinds of
      spectra data which are from the United States SDSS-DR8. Among these three
      methods, the rate of correct classification of the LMKNCN algorithm is higher
      than the other two algorithms or comparable and the average rate of correct
      classification is higher than the other two algorithms, especially for the
      identification of quasars. Experiment shows that the results in this work have
      important significance for studying galaxies, stars and quasars spectra
      classification.

PMID- 26197611
TI  - [Instrumentation and Application of a Portable Pretreating System for a Speedy
      Plasmon-Enhanced Raman Spectroscopy Detection Towards Food Safety].
AB  - The present paper developed a portable and fast sample pretreatment apparatus. It
      has many virtues like being portable, low power consumption and convenient
      operation, short extraction time and sound repeatability. Therefore, it can meet
      the requirements of on-site rapid detection pretreatment. The apparatus consists
      of four functional modules: ultrasonic extraction unit, heating unit, exhaust gas
      evaporation and absorption unit and control system. In addition, LED control
      panel and alarm device were designed. The whole treatment process needs three
      steps: ultrasonic extraction, liquid-liquid extraction and solvent evaporation by
      heating and pumping. For test of this apparatus performance, three real samples
      (pepper powder, pepper oil, bean sauce) containing banned additive Rhodamine B
      were taken as experiment objects. Compared with conventional laboratory
      pretreatment method, the PERS spectra achieved by two methods were little
      changed, but the experiment time was halved. In addition, the test results showed
      relative standard deviation less than +/-5%.

PMID- 26197612
TI  - [Establishment and Improvement of Portable X-Ray Fluorescence Spectrometer
      Detection Model Based on Wavelet Transform].
AB  - The concentration of Cr, Cu, Zn, As and Pb in soil was tested by portable X-ray
      fluorescence spectrometer. Each sample was tested for 3 times, then after using
      wavelet threshold noise filtering method for denoising and smoothing the spectra,
      a standard curve for each heavy metal was established according to the standard
      values of heavy metals in soil and the corresponding counts which was the average
      of the 3 processed spectra. The signal to noise ratio (SNR), mean square error
      (MSE) and information entropy (H) were taken to assess the effects of denoising
      when using wavelet threshold noise filtering method for determining the best
      wavelet basis and wavelet decomposition level. Some samples with different
      concentrations and H3 B03 (blank) were chosen to retest this instrument to verify
      its stability. The results show that: the best denoising result was obtained with
      the coif3 wavelet basis at the decomposition level of 3 when using the wavelet
      transform method. The determination coefficient (R2) range of the instrument is
      0.990-0.996, indicating that a high degree of linearity was found between the
      contents of heavy metals in soil and each X-ray fluorescence spectral
      characteristic peak intensity with the instrument measurement within the range (0
      1,500 mg . kg(-1)). After retesting and calculating, the results indicate that
      all the detection limits of the instrument are below the soil standards at
      national level. The accuracy of the model has been effectively improved, and the
      instrument also shows good precision with the practical application of wavelet
      transform to the establishment and improvement of X-ray fluorescence spectrometer
      detection model. Thus the instrument can be applied in on-site rapid screening of
      heavy metal in contaminated soil.

PMID- 26197613
TI  - [Study on the Spectral Characteristics of the Narrow-Band Filter in SHS].
AB  - The spectral response of spatial heterodyne spectroscopy (SHS) is determined by
      the spectrum property of narrow-band filter. As discussed in previous studies,
      the symmetric heterodyned interferogram of high frequency waves modulated by SHS
      and lack of sample lead to spectral confusion, which is associated with the true
      and ghost spectra. Because of the deviation from theoretical index of narrow-band
      filter in the process of coating, the boarded spectral response and middle wave
      shift are presented, and conditions in the theoretical Littrow wavelength made
      the effective wavelength range of SHS reduced. According to the measured curve of
      filter, a new wavenumber of zero spatial frequency can be reset by tunable laser,
      and it is easy for SHS to improve the spectral aliasing distortion. The results
      show that it is utilized to the maximum extent of the effective bandwidth by
      adjusting the grating angle of rotation to change the Littrow wavelength of the
      basic frequency, and the spectral region increased to 14.9 nm from original 12.9
      nm.

PMID- 26197614
TI  - [A Method for Selecting Self-Adoptive Chromaticity of the Projected Markers].
AB  - The authors designed a self-adaptive projection system which is composed of color
      camera, projector and PC. In detail, digital micro-mirror device (DMD) as a
      spatial light modulator for the projector was introduced in the optical path to
      modulate the illuminant spectrum based on red, green and blue light emitting
      diodes (LED). However, the color visibility of active markers is affected by the
      screen which has unknown reflective spectrum as well. Here active markers are
      projected spot array. And chromaticity feature of markers is sometimes submerged
      in similar spectral screen. In order to enhance the color visibility of active
      markers relative to screen, a method for selecting self-adaptive chromaticity of
      the projected markers in 3D scanning metrology is described. Color camera with 3
      channels limits the accuracy of device characterization. For achieving
      interconversion of device-independent color space and device-dependent color
      space, high-dimensional linear model of reflective spectrum was built. Prior
      training samples provide additional constraints to yield high-dimensional linear
      model with more than three degrees of freedom. Meanwhile, spectral power
      distribution of ambient light was estimated. Subsequently, markers' chromaticity
      in CIE color spaces was selected via maximization principle of Euclidean
      distance. The setting values of RGB were easily estimated via inverse transform.
      Finally, we implemented a typical experiment to show the performance of the
      proposed approach. An 24 Munsell Color Checker was used as projective screen.
      Color difference in the chromaticity coordinates between the active marker and
      the color patch was utilized to evaluate the color visibility of active markers
      relative to the screen. The result comparison between self-adaptive projection
      system and traditional diode-laser light projector was listed and discussed to
      highlight advantage of our proposed method.

PMID- 26197615
TI  - [Analysis of SPR Signal by Using Optimized Savitzky-Golay Filter].
AB  - The spectrum of surface plasmon resonance shows different amplitudes and peak
      widths with theeffects of resonant intensity and position, so it's necessary to
      develop the self-adaptive methods to guarantee the accurate positioning of SPR
      formant. Based on the optimized Savitzky-Golay filter, this paper presents a
      method for SPR spectrum, which can optimize the parameters (polynomial degree and
      window size) according to the characteristics of the real time SPR spectrum, and
      minimizes the Stein's unbiased risk estimate of the mean squared error, and it
      can be quickly solved by Monte-Carlo methods. It is confirmed that SURE can
      accurately reflect the trends and the results of the true MSE. The experiment
      measures the SPR signals of sucrose under different concentrations and
      integration time through the SPR system. By using the proposed method of optimal
      parameters on the SPR signal filtering, the results show that the repeatability
      error of the position of SPR formant is smaller compared with the fixed
      parameters, and does not increase with the addition of noise levels.

PMID- 26197616
TI  - [Research on Spectral Polarization Imaging System Based on Static Modulation].
AB  - The main disadvantages of traditional spectral polarization imaging system are:
      complex structure, with moving parts, low throughput. A novel method of spectral
      polarization imaging system is discussed, which is based on static polarization
      intensity modulation combined with Savart polariscope interference imaging. The
      imaging system can obtain real-time information of spectral and four Stokes
      polarization messages. Compared with the conventional methods, the advantages of
      the imaging system are compactness, low mass and no moving parts, no electrical
      control, no slit and big throughput. The system structure and the basic theory
      are introduced. The experimental system is established in the laboratory. The
      experimental system consists of reimaging optics, polarization intensity module,
      interference imaging module, and CCD data collecting and processing module. The
      spectral range is visible and near-infrared (480-950 nm). The white board and the
      plane toy are imaged by using the experimental system. The ability of obtaining
      spectral polarization imaging information is verified. The calibration system of
      static polarization modulation is set up. The statistical error of polarization
      degree detection is less than 5%. The validity and feasibility of the basic
      principle is proved by the experimental result. The spectral polarization data
      captured by the system can be applied to object identification, object
      classification and remote sensing detection.

PMID- 26197617
TI  - [AOTF-Based Imaging Spectrometer and Its Applications in the Identification of
      Metameric Targets].
AB  - For obtaining spectrum information and space distribution information of
      metameric targets at the same time, an AOTF-based imaging spectrometer was
      developed, which consists of a front imaging lens assembly, an AOTF filter
      imaging module, an AOTF driver, a plane array CCD, an image acquisition card and
      a PC. Under the control of the PC, a spectral image cube can be obtained by a
      fast wavelength scanning process, thereby the spectrum information of any point
      on the image is available. The developed imaging spectrometer, with a spectral
      range from 550-1,000 nm and a spectral resolution of 2.6 nm (@ 632 nm), and a
      less than 80 s switch time between any two wavelengths, has the characteristics
      of no mechanical moving part, low power dissipation and strong vibration
      resistance. The identification test of true and false roses and the information
      recovery experiment of altered physical evidence were carried out, The true and
      false roses were identified and the altered physical evidence was recovered, The
      experimental results showed that the imaging spectrometer has an excellent
      ability of identifying metameric targets, indicating a good application prospect.

PMID- 26197618
TI  - [Monitoring of Curing Temperature of Pouring Explosive Based on Fiber Bragg
      Grating].
AB  - For the first time, we real time measured released reaction heat between the
      binder and the curing agent in the curing process of cast explosive using fiber
      Bragg grating. In order to obtain the temperature in the process of pouring
      explosive casting real time and accurately, we designed the temperature
      monitoring system based on fiber Bragg grating. Given the risk of explosive
      component, long curing time and the requirements of constant temperature, a
      suitable measurement method for direct real-time monitoring has not been found.
      In recent years, due to its superior characteristics, fiber Bragg grating is
      widely used in the field of communication and sensing. We will make the collected
      reflection wavelength to convert real-time temperature displaying, utilizing
      linear relationship between fiber Bragg grating and temperature. Through WDM
      technology, seven grating points are written in two optical fibers to measure at
      the same time, and distribution trend of explosives internal temperature can be
      displayed in real time by multi-point distributed measurement. The curved design
      of the sensor not only improves the connection between sensor and jumper, but
      also benefits to place in oven. The txt data is made to draw a graph using origin
      software, and the changes in temperature in the curing process are displayed
      intuitively. The results show that this method is simple and high-precision, and
      meets the testing requirements of curing temperature of explosives.

PMID- 26197619
TI  - [Study of Spectral Property and Measurement of Linear Variable Filters].
AB  - Linear variable filters (LVF) are widely used in a variety of small rapid
      spectrometric detecting devices. In the present paper, the splitting property of
      LVF was studied, and the spectral-property expression in Gaussian form was given,
      and the relationship between indexes of expression and LVF center transmission,
      width of spectrum, and linear dispersion was specified. Measurement based on
      monochromator for imaging spectrometers calibration was introduced, the
      sensitivity for detection system was discussed, and the tolerance was analyzed.
      It was shown that the slit displacement of monochromator relative to the optical
      axle and the slope of LVF affect the detecting accuracy most, and the tolerance
      can be reduced by adjustment of optical path and structure to reach requirement.
      System was built and the detection for spectral property of sample LVF was made.
      The result of data processing indicates that MSE for center transmission
      detection was lower than 0.05%, and the accuracy of this method was proved.
      Reference-parameters of relevant system designing and calibrating based on the
      LVF can be provided by this method.

PMID- 26197620
TI  - [Adaptive "3R" De-Noising Algorithm Based on Near Infrared Bi-Spectrum].
AB  - Adaptive de-noising algorithm is proposed based on transmission spectrum and
      absorption spectrum of near infrared. Near infrared transmission spectrum and
      absorption spectrum collected synchronously are decomposed into intrinsic mode
      functions by ensemble empirical mode decomposition; the intrinsic mode function
      is a single frequency component. Correlations between intrinsic mode functions
      and transmission spectrum, absorption spectrum were calculated, and the
      correlation between intrinsic mode functions of transmission spectrum and
      absorption spectrum was also computed. The results show that the intrinsic mode
      function with minimum correlation coefficient should be noise component. The self
      correlation of this intrinsic mode function was analyzed to judge whether the
      intrinsic mode function is noise. IF the self-correlation is very large at the
      midpoint and is zero or very small at the other point of the spectrum, then the
      intrinsic mode function is noise component for judgment, based on which "3R"
      algorithm is named to judge whether the intrinsic mode function is noise
      component. Removing noise component, constructing spectral signal and circulating
      the previous decomposition was conducted, and the noise reduction process was
      ended until it did not meet the "3R" rule. To do experiment on the simulated
      spectrum with noise, the effect of de-noising with "3R" algorithm is better than
      EMD and EEMD low pass filter, and it is not so good as wavelet decomposition. In
      the real spectrum testing, the model was established between spectra treated by
      above methods with chlorophyll on three layers. BP neural network, and the model
      de-noised by "3R" method has the biggest correlation coefficient and prediction
      coefficient, but the smallest correction standard error and prediction standard
      error. "3R" method's effects on the peak position and peak intensity of spectrum
      are the smallest among the four kinds of de-noising methods. Experiments show
      that the "3R" algorithm based on bi-spectrum can be used for near infrared
      spectra de-nosing without presetting the number of iterations, there is no need
      to consider layers of decomposition, also no need of basis function, and the
      adaptability is very strong.

PMID- 26197621
TI  - [The healing wine of Tokaj, Hungary].

PMID- 26197622
TI  - [Holistic approach in ancient Egypt].

PMID- 26197623
TI  - Living with Urinary Incontinence.

PMID- 26197624
TI  - An Example of Translating Value-Based Purchasing Into Value-Based Care.
AB  - The Affordable Care Act (ACA) (2010) launch of Medicare Value-Based Purchasing
      (VBP) has become the platform for buyers of health care to hold health care
      providers accountable for demonstrating high-quality, cost-effective care for
      Medicare recipients across the trajectory of care practitioners and settings
      (Gardner, 2013; VanLare & Conway, 2012). The Centers for Medicare and Medicaid
      Services (CMS), authorized under the ACA, specified quality measures that will
      best advance the National Quality strategic objectives and build upon the
      Hospital Inpatient Quality Reporting infrastructure (U.S. Department of Health &
      Human Services [DHHS], 2013). The quality performance measure domains for fiscal
      year 2013 focused on Clinical Process of Care and Patient Experience of Care
      domains. Strategically, quality measures will expand to include delivery of care
      models, and coordinated care focused on promoting health wellness and health
      maintenance within the community setting (VanLare & Conway, 2012). Value-based
      purchasing affords nursing the opportunity to lead the charge in developing
      innovative delivery of care models to improve the quality of care at a lower cost
      and shift from providing sick care toward population-focused, preventative, and
      health promotion care (Gofin, Gofin, & Stimpson, 2014; Marsh, Diers, & Jenkins,
      2013).

PMID- 26197625
TI  - Pain Management in the Post-Operative Pediatric Urologic Patient.
AB  - Optimizing pain management is a component of enhanced perioperative recovery for
      children undergoing urologic surgery. Incisional pain and discomfort from bladder
      spasms are two types of pain associated with bladder surgery. A child's
      developmental level and verbal skills must be considered when selecting pain
      assessment tools. Assessing pain location, type, and intensity is essential in
      developing a multimodal plan of care for post-operative pain. Pharmacological
      interventions provide effective pain management, which facilitates early
      ambulation, return to oral intake, and recovery. Pre-operative preparation, non
      pharmacological interventions, and parental presence help decrease anxiety and
      promote comfort, as well as support a child's coping skills.

PMID- 26197627
TI  - Erectile Dysfunction in the Older Adult Male.
AB  - Erectile dysfunction (ED) in the older adult male is a significant problem
      affecting more than 75% of men over 70 years of age in the United States. Older
      men have an increased likelihood of developing ED due to chronic disease,
      comorbid conditions, and age-related changes. Research has demonstrated that
      while the prevalence and severity of ED increases with age, sexual desire often
      remains unchanged. This article discusses the clinical picture of ED, including
      relevant pathophysiology, clinical presentation, and evaluation and treatment
      options.

PMID- 26197626
TI  - Understanding Urinary Incontinence in Adults.
AB  - This article aims to assist urologic nurses in the assessment and management of
      adults with urinary incontinence, with special consideration given to the
      geriatric patient. Additionally, discussion will include classifications of the
      disorder, risk factors, and applicable age-related impacts.

PMID- 26197628
TI  - Evaluation of a Nurse-Driven Protocol to Remove Urinary Catheters: Nurses'
      Perceptions.
AB  - This article describes nurses' perceptions of the effect of a nurse-driven
      protocol in a Magnet-designated hospital. Post-protocol implementation data
      indicate improved job ease and positive patient feedback following protocol
      implementation. Younger or less-experienced nurses were likely to use the
      protocol.

PMID- 26197629
TI  - A Moral Distress: Chewing Gum (Harmful or Helpful?).

PMID- 26197630
TI  - Dr. Pier Broadnax Discusses the RN to BSN Program at UDC with NurseJournal.org.

PMID- 26197631
TI  - Remembering Dr. Anna Bailey Coles (Founding Dean of the Howard University College
      of Nursing).

PMID- 26197632
TI  - "Core Communication Competencies in Patient-Centered Care" by Anita D. Boykins.

PMID- 26197633
TI  - Exploratory Study of Breast Cancer Screening Practices of Urban Women: A Closer
      Look at Who Is and Is Not Getting Screened.
AB  - Several initiatives have been embarked upon over the past decade to encourage
      breast cancer screening and follow-up among women who reside in urban
      communities. With these efforts, data revealed that many women do not receive the
      recommended breast cancer screening. Studies have been published in scientific
      literature that explored barriers faced by women relative to breast cancer
      screening. But, only a few reports have been published of efforts initiated to
      define the limits of characteristics of women who have and women who have not
      been screened. This cross-sectional exploratory study was designed to examine the
      breast cancer screening practices of women 40-74 years of age and older who
      reside in a densely populated metropolitan community of S.E. Wisconsin, and to
      identify and compare the characteristics of women who report breast cancer
      screening and with characteristics of women who report no breast cancer
      screening. The organizing framework for this study was derived from the United
      States Department of Health and Human Services Determinants of Health Model. An
      investigator-designed instrument was used to assess the influence of age, family
      history of breast cancer insurance status, characteristics of residential
      neighborhood and local access to breast care on breast cancer screening. While
      the majority of the women surveyed reported breast cancer screening, less than
      half of the women reported screening that was consistent with recommended breast
      cancer screening guidelines (i.e. annual mammography and annual clinical breast
      examination). Deficits in breast cancer screening were noted most among women who
      were uninsured, with no knownfamily history of breast cancer, who resided in low
      income neighborhoods, inner-city neighborhoods and neighborhoods without
      facilities for primary breast care. The results of this study demonstrate the
      needfor clinicians, health care administrators and advocates committed to breast
      cancer detection and control within targeted communities. They must carefully
      assess the impact of individual, social and structural factors on breast cancer
      screening, and the need to design initiatives specifically targeted to women who
      have received less than optimal or no breast cancer screening.

PMID- 26197634
TI  - African American Wives and Perceived Stressful Experiences: Providing Care for
      Stroke Survivor Spouses.
AB  - This research used a quantitative design to explore perceived stress experiences
      of African American wives in the care of spouses who are stroke survivors. The
      wives as caregivers (44.7%) were participants from rural communities in the
      southeastern region of North Carolina. These wives, although many had employment
      outside of the home, provided duties including activities of daily living (ADL)
      and all other domestic tasks. They were forced into the caregiving role, although
      many were often not prepared, and experienced much stress related to a lack of
      knowledge, training and minimum assistance from other family members. A nursing
      implication must include extensive discharge planning with an emphasis on
      education and training prior to discharge. More research in reference to African
      American wives as caregivers is needed to provide an adequate knowledge base in
      not only caring for their spouses, but also themselves.

PMID- 26197635
TI  - Pilot Testing HIV Prevention in an Afro Caribbean Faith-Based Community.
AB  - This research attempted to test an HIV prevention intervention for Afro-Caribbean
      female teens. The purpose was to improve knowledge and attitudes concerning
      HIV/AIDS, improve mother-daughter sexual communication, and to reduce risky
      sexual behaviors. Using a community-based approach, sixty mother and daughter
      pairs were randomly assigned. One condition was experimental using the Making
      Proud Choices Caribbean Style (MPCCS); another was a comparison of General Health
      Education. Independent t-tests were used for analysis between the pretest,
      posttest and 90 days posttests. MPCCS indicated clear usage with other Caribbean
      teens. This study helped to support the theory when Afro-Caribbean (AC) teens
      feel they need to become sexually active (subjective norm), and have referent
      support (parental support), they may blend values, knowledge, and skills (control
      beliefs), and are likely to make proud choices to reduce risky sexual behavior in
      minimizing HIV in their communities.

PMID- 26197636
TI  - Sentinel Event Alert. New Alert Discusses Safe Use of Health Information
      Technology.

PMID- 26197637
TI  - Deeming-Related Revisions to Requirements for Hospitals and Critical Access
      Hospitals. Additions Changes Resutlting from CMS Final Rule.

PMID- 26197638
TI  - Testing Fire Pumps, Standpipe Water Flow, and Kitchen-Based Fire-Extinguishing
      Systems. Delving Further into EC.02.03.05.

PMID- 26197639
TI  - UPDATED: Policies Regarding Accreditation Status Following Cessation of Services.

PMID- 26197641
TI  - HOW ANALYTICS TAKES THE UNKNOWNS OUT OF ACOs. Technology helping organizations
      connect the dots and provide better care.

PMID- 26197642
TI  - THE BIG WISH FOR ICD:10 EASIER PAYMENT. Stakeholders who see the ICD-10 finish
      line still are looking for tools to simplify cash flow.

PMID- 26197643
TI  - HOW FAR TO TRUE INTEROPERABILITY? Efforts ramp up to overcome barriers preventing
      the exchange of digital health information.

PMID- 26197644
TI  - BIG DATA IMPROVES CARE AT CHILDREN'S IN ATLANTA. Small tech research project is a
      launchpad for other studies seeking to improve patient care.

PMID- 26197645
TI  - THE INTERNAL COMBUSTION OF EHRs.

PMID- 26197646
TI  - Virtual Visits.

PMID- 26197647
TI  - New Speak Up Infographic on Medical Imaging Tests.

PMID- 26197648
TI  - Equipment, Utility Systems, and Education Revisions for Deemed Ambulatory
      Surgical Centers.

PMID- 26197649
TI  - Revised Survey Eligibility Criteria for Five Programs.

PMID- 26197650
TI  - Caution: E-cigarettes Pose Potential Hazards. Follow Standards and Update Smoking
      Policies to Maintain compliance.

PMID- 26197651
TI  - Standards Revisions for Psychiatric Hospitals with Deemed Status.

PMID- 26197652
TI  - Revisions to Advanced Certification for Palliative Care Requirements.

PMID- 26197653
TI  - Myocarditis And Pericarditis In The Pediatric Patient: Validated Management
      Strategies.
AB  - Myocarditis and pericarditis are inflammatory conditions of the heart commonly
      caused by viral and autoimmune etiologies, although many cases are idiopathic.
      Emergency clinicians must maintain a high index of suspicion for these
      conditions, given the rarity and often nonspecific presentation in the pediatric
      population. Children with myocarditis may present with a variety of symptoms,
      ranging from mild flu-like symptoms to overt heart failure and shock, whereas
      children with pericarditis typically present with chest pain and fever. The
      cornerstone of therapy for myocarditis includes aggressive supportive management
      of heart failure, as well as administration of inotropes and antidysrhythmic
      medications, as indicated. Children often require admission to an intensive care
      setting. The acute management of pericarditis includes recognition of tamponade
      and, if identified, the performance of pericardiocentesis. Medical therapies may
      include nonsteroidal anti-inflammatory drugs and colchicine, with steroids
      reserved for specific populations. This review focuses on the evaluation and
      treatment of children with myocarditis and/or pericarditis, with an emphasis on
      currently available medical evidence.

PMID- 26197654
TI  - Responding to failures.

PMID- 26197655
TI  - 'I suppose in the war you just delivered them, like you did when it wasn't the
      war. I don't know if it was very different'.

PMID- 26197656
TI  - The 'more mature' midwife.

PMID- 26197657
TI  - Are you calling me fat?

PMID- 26197659
TI  - The problem with comparisons.

PMID- 26197658
TI  - POSTNATAL CHANGES.

PMID- 26197660
TI  - WORKING TOGETHER.

PMID- 26197661
TI  - RESEARCH. A postnatal clinic run by student midwives as a means of learning?

PMID- 26197662
TI  - Behaviour change techniques that reduce the decline in women's physical activity
      in pregnancy.

PMID- 26197663
TI  - How to ... Assess fitness for waterbirth.

PMID- 26197664
TI  - Crystal gazing predicting the future of childbirth.

PMID- 26197665
TI  - Dealing with DSD.

PMID- 26197666
TI  - The impact of the Kirkup report.

PMID- 26197667
TI  - Lifting the lid on revalidation.

PMID- 26197668
TI  - Helping vulnerable mothers.

PMID- 26197669
TI  - Rewarding innovation.

PMID- 26197670
TI  - Supporting midwifery beyond our borders.

PMID- 26197671
TI  - In whose best interest?

PMID- 26197672
TI  - Ebola: a dilemma for UK maternity services.

PMID- 26197673
TI  - Tipping point to obesity.

PMID- 26197674
TI  - Mums' Midwife of the Year Award.

PMID- 26197675
TI  - Breastfeeding as birth control.

PMID- 26197676
TI  - Continuity of carer for better births.

PMID- 26197677
TI  - Continuing Florence's work.

PMID- 26197678
TI  - A crucial interface.

PMID- 26197679
TI  - Advocates for patient safety.

PMID- 26197680
TI  - Judge grills Red Cross over sacking of EN.

PMID- 26197681
TI  - Pressure injury prevention pilot study: a follow-up.

PMID- 26197682
TI  - Violence in our health sector.

PMID- 26197683
TI  - Power in partnership--maternity reform over the past decade.

PMID- 26197684
TI  - CLOSING THE GAP--a Queensland nurse's tale.

PMID- 26197685
TI  - Classification and Epidemiology of Traumatic Dentoalveolar Injuries in Dogs and
      Cats: 959 Injuries in 660 Patient Visits (2004-2012).
AB  - The objective of this study was to determine the epidemiology of traumatic
      dentoalveolar injuries (TDI) in dogs and cats and to evaluate the applicability
      of a human classification system for TDI in dogs and cats. All patients diagnosed
      with a TDI were identified from the University of Wisconsin-Madison School of
      Veterinary Medicine Dentistry and Oral Surgery Service case log and the hospital
      patient processing software. The study population consisted of 621 dogs and cats,
      in a total of 660 patient visits from 2004 to 2012, admitted for oral treatment
      and subsequently diagnosed with at least one TDI Medical records including
      diagnostic imaging studies were reviewed to group the injury according to a
      classification system used in humans for TDI. Patient signalment, tooth injured,
      and number of injuries per patient were recorded and tabulated. The overall
      prevalence of TDI was 26.2%. The mean +/- SD number of TDI per patient was 1.45
      +/- 0.85. All 14 classes of TDI recognized by the classification system utilized
      in humans were identified, and all (100%) TDI identified in this study were
      classifiable using this system. Enamel-dentin-pulp fracture was the most common
      TDI (49.6%). The most commonly injured teeth were the mandibular or maxillary
      canine teeth (35.5%). The most common age for dogs and cats with TDI were 3-6
      years (33.0%) and 7-10 years (31.3%). With a frequency of 1 in 4 animals, TDI are
      common and represent a significant pet health concern. Most TDI are considered
      severe and require timely, and sometimes immediate, treatment. The adoption and
      utilization of a complete classification system, such as the one used in this
      study, is recommended in order to improve future epidemiological study of TDI in
      animals.

PMID- 26197686
TI  - Effect of Frequency of Brushing Teeth on Plaque and Calculus Accumulation, and
      Gingivitis in Dogs.
AB  - The efficacy of brushing the teeth of beagle dogs in a randomized, controlled,
      blinded study design using a clearly-defined brushing technique was evaluated for
      4 brushing frequencies: brushing daily, brushing every other day, brushing weekly
      and brushing every other week, compared with no brushing in a control group of
      dogs. All dogs were fed a standard dry kibble diet during the study. Standard
      plaque, calculus, and gingivitis indices were used to score the teeth. A 'clean
      tooth' model was used. No gingival or non-gingival lacerations or other signs of
      injury to oral tissues were found at the end of the 28 day trial period. Brushing
      more frequently had greater effectiveness in retarding accumulation of plaque and
      calculus, and reducing the severity of pre-existing gingivitis. Brushing daily or
      every other day produced statistically significant improved results compared with
      brushing weekly or every other week. Based on the results of this study, daily
      brushing is recommended.

PMID- 26197687
TI  - Suspect Odontogenic Infection Etiology for Canine Lymphoplasmacytic Rhinitis.
AB  - The role of odontogenic infection as an etiology for lymphoplasmacytic rhinitis
      in dogs was evaluated. An association between odontogenic infection and
      inflammatory rhinitis was identified in 55% of cases evaluated. Odontogenic
      infection was unlikely or undetermined in 10% and 35% of the cases, respectively.
      Cases of lymphoplasmacytic rhinitis had roentgen signs associated with endodontic
      disease, periodontal disease, or retained tooth roots in 60%, 45%, and 25% of the
      cases, respectively. A collaborative team based approach assessing inflammatory
      nasal disease is recommended. Based on the history and signalment of the
      individual patient, diagnostic modalities should be chosen wisely. In some cases,
      oral examination and intraoral radiographs may be a more direct and cost
      effective approach for diagnosis and treatment of inflammatory rhinitis.

PMID- 26197688
TI  - Feline Oral Squamous Cell Carcinoma: Clinical Manifestations and Literature
      Review.
AB  - Squamous cell carcinoma (SCC) is the most commonly encountered malignant oral
      tumor in cats. The etiology of this locally invasive tumor is likely
      multifactorial. Several risk factors have been identified, including the use of
      flea collars, and a history of feeding canned food and canned tuna. Clinical
      signs vary depending on tumor location. The tumor commonly arises from the
      gingiva and mucosa of the maxilla, mandible, tongue, sublingual area, or
      tonsillar region. Maxillary SCC commonly presents clinically as an ulcerative
      lesion, whereas mandibular SCC is commonly proliferative, expansile, and firm.
      Lingual/sublingual SCC may be ulcerative, necrotic, infiltrative, or
      proliferative. In general, feline oral SCC is an invasive and malignant neoplasm
      regardless of its location. Surgery, radiation therapy, chemotherapy and
      combinations thereof have been attempted with rarely a satisfactory response.
      Currently, cures are obtained only in a small subset of cats whose tumors are
      amenable to complete resection, or where resection with microscopic residual
      disease is followed by definitive radiation therapy. A multimodal treatment
      approach likely offers the best chance of success. For cats with advanced
      disease, palliative care may improve patients' quality of life, albeit
      transiently. Sequelae associated with tumor progression and local tissue
      destruction often result in euthanasia of feline patients with oral SCC.

PMID- 26197689
TI  - Traumatic Intrusion of a Maxillary Canine Tooth: 3 Cases.
AB  - Of the six recognized types of tooth luxation injuries, intrusion generally
      carries the most guarded long-term prognosis due to the high risk of
      complications, including root resorption, ankylosis, marginal bone loss, and pulp
      canal obliteration or necrosis. The degree of traumatic intrusion and stage of
      root development affects the outcome and treatment planning. This report
      describes the clinical history, oral and radiographic examination findings, and
      rationale for surgical extraction in 2 dogs and 1 cat with traumatic intrusion of
      a maxillary canine tooth.

PMID- 26197690
TI  - Focal Gingival Hyperplasia in a Donkey (Equus asinus).

PMID- 26197691
TI  - Maxillary Third Incisor Tooth Extraction in the Dog.

PMID- 26197692
TI  - The SGR is gone, but are nephrologists ready for P4P?

PMID- 26197693
TI  - ACOs, bundling, continue the assault on private medical practice.

PMID- 26197694
TI  - Finding consistency in Medicare's quality ratings for dialysis providers.
AB  - As of January 2015, the Centers for Medicare & Medicaid Services (CMS) now
      publishes two sets of quality rankings for dialysis facilities: performance
      ratings tied to the Quality Incentive Program (QIP), and "star ratings" published
      on the Dialysis Facility Compare website. We sought to compare the two ratings
      and see how consistent they are for a matched set of dialysis facilities that
      have ratings on both programs. While the two quality rating programs have
      somewhat different objectives, both ratings are made available to patients to
      assist them in understanding the quality of care they can expect to receive from
      a given dialysis facility. Consistency of the ratings will be important to their
      acceptance by both patients and providers as valid measures of relative quality.

PMID- 26197695
TI  - New studies look at value of nocturnal HD.

PMID- 26197696
TI  - Back in the saddle: How nocturnal dialysis helped me get my life back.

PMID- 26197697
TI  - A quality improvement project: Strategies to reduce intradialytic hypotension in
      hemodialysis patients.
AB  - Intradialytic hypotension is defined as a decrease in systolic blood pressure by
      >= 20 mm Hg or a decrease in mean arterial pressure by 10 mm Hg, and is
      associated with symptoms that include abdominal discomfort, yawning, sighing,
      nausea, vomiting, muscle cramps, restlessness, dizziness or fainting, and
      anxiety. The incidence of a symptomatic reduction in blood pressure during (or
      immediately following) dialysis ranges from 15-50% of dialysis sessions. It is a
      major cause for morbidity in elderly hemodialysis patients and those with
      cardiovascular compromise. It impairs patient well-being, limits ultrafiltration,
      and increases the risk for coronary and cerebral ischemic events as well as
      vascular access thrombosis. Several studies have shown a poorer survival in
      dialysis patients who experience frequent hypotensive episodes on dialysis as
      opposed to those who do not. In our outpatient dialysis unit, we identified that
      9% of our dialysis patients experienced a decrease in their systolic blood
      pressure to below 80 during dialysis. The purpose of this quality improvement
      project was to study the factors associated with intradialytic hypotension in
      these patients and institute appropriate measures to mitigate this issue. Another
      aim was to educate the dialysis staff on how to manage these patients. Patients
      were selected using data from weekly rounding reports and orders were written for
      interventions including ultrafiltration profiling, cool (36 degrees C) dialysate,
      weight-based ultrafiltration, etc. Outcomes were studied over a period of 3
      months. We found that up to 40% of patients experienced an improvement in their
      blood pressure profile over the period of the study, suggesting that simple
      changes to dialysis prescription can result in a significant reduction in the
      incidence of intradialytic hypotension.

PMID- 26197698
TI  - Life on the bridge: A journey with dialysis.

PMID- 26197699
TI  - Be proactive about monitoring your potassium.

PMID- 26197700
TI  - Speak UP! Take charge of your health! Become a kidney patient advocate on Capitol
      Hill!

PMID- 26197703
TI  - Risk of Recurrent Neurologic Stroke or Transient Ischemic Attack in Patients with
      Cryptogenic Stroke and Intrapulmonary Shunt.
AB  - BACKGROUND AND PURPOSE: Cardio-embolic phenomenon is believed to underlie a
      significant proportion of cryptogenic strokes. We recently showed that
      intrapulmonary shunt (IPS) was associated with cryptogenic stroke and transient
      ischemic attack (TIA). We hypothesized that patients with prior cryptogenic
      stroke or TIA that had an IPS were at a higher risk for recurrent ischemic
      events. METHODS: The population included subjects with cryptogenic
      cerebrovascular accident (CVA) or TIA. Inclusion criteria were age >=18 years,
      sinus rhythm, and clinically indicated transesophageal echocardiography (TEE).
      Exclusion criteria were hemorrhagic CVA, septal defect, and patent foramen.
      Patients were followed from index TEE. RESULTS: Of 71 patients, 8 were lost to
      follow-up. A total of 23 patients had and 40 were without IPS. Average follow-up
      duration was 38.3 +/- 19.2 months. Groups were similar at baseline. There was no
      significant difference in the recurrence of ischemic CVA or TIA in the IPS versus
      non-IPS groups (0% vs. 7.5%; P = NS). There was no difference between the
      incidence of hemorrhagic CVA in the IPS and non-IPS groups (4.3% vs. 5.0%; P =
      NS). The proportion of patients on warfarin in the IPS group was significantly
      higher compared to the non-IPS group (17.4% vs. 0%; P < 0.05). CONCLUSIONS:
      Patients with IPS and cryptogenic stroke or TIA did not have a higher recurrence
      of ischemic cerebral events. Warfarin was significantly higher at follow-up in
      the IPS compared to the non-IPS group, which may explain these findings. A study
      randomizing patients with IPS and cryptogenic stroke or TIA to warfarin or no
      warfarin would be of great interest.

PMID- 26197704
TI  - The Professionalization of International Disaster Response: It Is Time for
      Midwives to Get Ready.
AB  - Disasters and humanitarian emergencies due to natural or human origins result in
      severe and often prolonged suffering of the affected population. Midwives have a
      role to play in providing assistance because women and their infants experiencing
      such crises have unique vulnerabilities and needs. This article introduces
      midwives and other women's health care practitioners to international
      humanitarian emergency response efforts and describes preparation and training
      activities they can undertake to get ready to volunteer with an international
      health aid agency. Various clinical realities and challenges are discussed,
      including recommended priorities for providing reproductive health care in
      disaster zones. Common ethical dilemmas in crisis health care settings are also
      reviewed. By arriving in the field well prepared to participate and collaborate,
      midwives can make substantial contributions to the safety, health, and comfort of
      women and their families who have experienced a natural disaster, armed conflict,
      or disease epidemic. 

PMID- 26197706
TI  - Improving Oenococcus oeni to overcome challenges of wine malolactic fermentation.
AB  - Oenococcus oeni is crucial for winemaking, bringing stabilization,
      deacidification, and sensory impacts through malolactic fermentation (MLF) to
      most wine styles. The poor nutritional make-up of wine together with typically
      low processing temperatures and pH and high ethanol content and sulfur dioxide
      (SO2) hinder O. oeni growth and activity. Production delays and interventions
      with starter cultures and nutritional supplements have significant cost and
      quality implications; thus, optimization of O. oeni has long been a priority. A
      range of optimization strategies, some guided by detailed characterization of O.
      oeni, have been exploited. Varying degrees of success have been seen with
      classical strain selection, mutagenesis, gene recombination, genome shuffling,
      and, most recently, directed evolution (DE). The merits, limitations, and future
      prospects of each are discussed. 

PMID- 26197705
TI  - Identification and functional characterization of natural human melanocortin 1
      receptor mutant alleles in Pakistani population.
AB  - Melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor of the melanocyte's
      plasma membrane, is a major determinant of skin pigmentation and phototype. Upon
      activation by alpha-melanocyte stimulating hormone, MC1R triggers the cAMP
      cascade to stimulate eumelanogenesis. We used whole-exome sequencing to identify
      causative alleles in Pakistani families with skin and hair hypopigmentation. Six
      MC1R mutations segregated with the phenotype in seven families, including a
      p.Val174del in-frame deletion and a p.Tyr298* nonsense mutation, that were
      analyzed for function in heterologous HEK293 cells. p.Tyr298* MC1R showed no
      agonist-induced signaling to the cAMP or ERK pathways, nor detectable agonist
      binding. Conversely, signaling was comparable for p.Val174del and wild-type in
      HEK cells overexpressing the proteins, but binding analysis suggested impaired
      cell surface expression. Flow cytometry and confocal imaging studies revealed
      reduced plasma membrane expression of p.Val174del and p.Tyr298*. Therefore,
      p.Tyr298* was a total loss-of-function (LOF) allele, while p.Val174del displayed
      a partial LOF attribute. 

PMID- 26197707
TI  - Antidiabetogenic effects of hydroxychloroquine on insulin sensitivity and beta
      cell function: a randomised trial.
AB  - AIMS/HYPOTHESIS: Hydroxychloroquine (HCQ), an antimalarial drug with anti
      inflammatory properties, is employed in rheumatic diseases. In observational
      studies, patients with rheumatic diseases treated with HCQ have a lower risk of
      developing diabetes. However, the physiological mechanisms remain unexplained. We
      hypothesised that HCQ may have favourable effects on insulin sensitivity and/or
      beta cell function. METHODS: This was a randomised, double-blind, parallel-arm
      (placebo vs HCQ 400 mg/day) trial at the University of Pittsburgh. Randomisation
      was conducted by a computer system with concealment by sealed envelopes.
      Treatment duration was 13 +/- 1 weeks. Randomised participants (HCQ n = 17;
      placebo n = 15) were non-diabetic volunteers, age >18, overweight or obese, with
      one or more markers of insulin resistance. All participants were included in
      intention-to-treat analysis. Outcomes were changes in insulin sensitivity and
      beta cell function measured by intravenous glucose tolerance tests and minimal
      model analysis. RESULTS: There was a positive change in insulin sensitivity with
      HCQ but not placebo (mean +/- SEM: +20.0% +/- 7.1% vs -18.4% +/- 7.9%,
      respectively; p < 0.01; difference: 38.3% +/- 10.6%; 95% CI: 17%, 60%).
      Improvement in beta cell function was also observed with HCQ but not placebo
      (+45.4% +/- 12.3% vs -19.7% +/- 13.6%; p < 0.01; difference: 65% +/- 19%; 95% CI:
      27%, 103%). There were modest treatment effects on fasting plasma glucose and
      HbA(1c) (p < 0.05) but circulating markers of inflammation (IL-6, IL-1, TNF
      alpha, soluble intercellular adhesion molecule) were not affected in either
      group. In contrast, adiponectin levels increased after HCQ treatment but not
      after placebo (+18.7% vs +0.7%, respectively; p < 0.001). Both low- and high
      molecular-weight adiponectin forms accounted for the increase. There were no
      serious or unexpected adverse effects. CONCLUSIONS/INTERPRETATION: HCQ improves
      both beta cell function and insulin sensitivity in non-diabetic individuals.
      These metabolic effects may explain why HCQ treatment is associated with a lower
      risk of type 2 diabetes. An additional novel observation is that HCQ improves
      adiponectin levels, possibly being a mediator of the favourable effects on
      glucose metabolism. Our findings suggest that HCQ is a drug with considerable
      metabolic effects that warrant further exploration in disorders of glucose
      metabolism. TRIAL REGISTRATION: Clinicaltrials.gov NCT01326533 FUNDING: This
      study was funded by National Institutes of Health no. 5R21DK082878, UL1-RR024153
      and UL-1TR000005.

PMID- 26197708
TI  - Extremely rapid increase in fatty acid transport and intramyocellular lipid
      accumulation but markedly delayed insulin resistance after high fat feeding in
      rats.
AB  - AIMS/HYPOTHESIS: The mechanisms for diet-induced intramyocellular lipid
      accumulation and its association with insulin resistance remain contentious. In a
      detailed time-course study in rats, we examined whether a high-fat diet increased
      intramyocellular lipid accumulation via alterations in fatty acid translocase
      (FAT/CD36)-mediated fatty acid transport, selected enzymes and/or fatty acid
      oxidation, and whether intramyocellular lipid accretion coincided with the onset
      of insulin resistance. METHODS: We measured, daily (on days 1-7) and/or weekly
      (for 6 weeks), the diet-induced changes in circulating substrates, insulin,
      sarcolemmal substrate transporters and transport, selected enzymes,
      intramyocellular lipids, mitochondrial fatty acid oxidation and basal and insulin
      stimulated sarcolemmal GLUT4 and glucose transport. We also examined whether
      upregulating fatty acid oxidation improved glucose transport in insulin-resistant
      muscles. Finally, in Cd36-knockout mice, we examined the role of FAT/CD36 in
      intramyocellular lipid accumulation, insulin sensitivity and diet-induced glucose
      intolerance. RESULTS: Within 2-3 days, diet-induced increases occurred in
      insulin, sarcolemmal FAT/CD36 (but not fatty acid binding protein [FABPpm] or
      fatty acid transporter [FATP]1 or 4), fatty acid transport and intramyocellular
      triacylglycerol, diacylglycerol and ceramide, independent of enzymatic changes or
      muscle fatty acid oxidation. Diet-induced increases in mitochondria and
      mitochondrial fatty acid oxidation and impairments in insulin-stimulated glucose
      transport and GLUT4 translocation occurred much later (>=21 days). FAT/CD36
      ablation impaired insulin-stimulated fatty acid transport and lipid accumulation,
      improved insulin sensitivity and prevented diet-induced glucose intolerance.
      Increasing fatty acid oxidation in insulin-resistant muscles improved glucose
      transport. CONCLUSIONS/INTERPRETATIONS: High-fat feeding rapidly increases
      intramyocellular lipids (in 2-3 days) via insulin-mediated upregulation of
      sarcolemmal FAT/CD36 and fatty acid transport. The 16-19 day delay in the onset
      of insulin resistance suggests that additional mechanisms besides
      intramyocellular lipids contribute to this pathology.

PMID- 26197709
TI  - BH3-only protein Bim is associated with the degree of Helicobacter pylori-induced
      gastritis and is localized to the mitochondria of inflammatory cells in the
      gastric mucosa.
AB  - BH3-only protein, Bim, is a pro-apoptotic protein that mediates mitochondria
      dependent cell death. However, the role of Bim in Helicobacter pylori-associated
      gastritis remains unclear. This study aimed to assess the cellular localization
      of Bim and its possible role in H. pylori-induced gastritis. The study was
      conducted on biopsy specimens obtained from 80 patients who underwent upper
      gastrointestinal endoscopy (H. pylori-negative: n=30, positive: n=50).
      Association between Bim mRNA expression and severity of gastritis was evaluated
      and the localization of Bim was examined by immunofluorescence. Bim mRNA
      expression was positively correlated with the degree of gastritis, as defined by
      the Sydney system. Immunohistochemical analysis confirmed increased Bim
      expression in H. pylori-infected gastric mucosa compared with uninfected mucosa
      in both humans and mice. Bim localized in myeloperoxidase- and CD138-positive
      cells of H. pylori-infected lamina propria and submucosa of the gastric tract,
      indicating that this protein is predominantly expressed in neutrophils and plasma
      cells. In contrast, Bim did not localize in CD20-, CD3-, or CD68-positive cells.
      Bim was expressed in the mitochondria, where it was partially co-localized with
      activated Bax and cleaved-PARP. In conclusion, Bim is expressed in neutrophils
      and plasma cells in H. pylori-associated gastritis, where it may participate in
      the termination of inflammatory response by causing mitochondria-mediated
      apoptosis in specific leucocytes. 

PMID- 26197710
TI  - Knock-in fibroblasts and transgenic blastocysts for expression of human FGF2 in
      the bovine beta-casein gene locus using CRISPR/Cas9 nuclease-mediated homologous
      recombination.
AB  - Many transgenic domestic animals have been developed to produce therapeutic
      proteins in the mammary gland, and this approach is one of the most important
      methods for agricultural and biomedical applications. However, expression and
      secretion of a protein varies because transgenes are integrated at random sites
      in the genome. In addition, distal enhancers are very important for
      transcriptional gene regulation and tissue-specific gene expression. Development
      of a vector system regulated accurately in the genome is needed to improve
      production of therapeutic proteins. The objective of this study was to develop a
      knock-in system for expression of human fibroblast growth factor 2 (FGF2) in the
      bovine beta-casein gene locus. The F2A sequence was fused to the human FGF2 gene
      and inserted into exon 3 of the beta-casein gene. We detected expression of human
      FGF2 mRNA in the HC11 mouse mammary epithelial cells by RT-PCR and human FGF2
      protein in the culture media using western blot analysis when the knock-in vector
      was introduced. We transfected the knock-in vector into bovine ear fibroblasts
      and produced knock-in fibroblasts using the clustered regularly interspaced short
      palindromic repeats (CRISPR)/Cas9 system. Moreover, the CRISPR/Cas9 system was
      more efficient than conventional methods. In addition, we produced knock-in
      blastocysts by somatic cell nuclear transfer using the knock-in fibroblasts. Our
      knock-in fibroblasts may help to create cloned embryos for development of
      transgenic dairy cattle expressing human FGF2 protein in the mammary gland via
      the expression system of the bovine beta-casein gene. 

PMID- 26197712
TI  - Prevalence of hypertension among federal ministry civil servants in Addis Ababa,
      Ethiopia: a call for a workplace-screening program.
AB  - BACKGROUND: The prevalence of hypertension (HTN) is increasing rapidly in
      Ethiopia, but data are limited on hypertension prevalence in specific workplaces.
      Therefore, the aim of this study was to assess the prevalence and associated
      factors of hypertension among federal ministry civil servants. METHODS:
      Institutional based cross sectional study was conducted from February to April
      2014. Simple random sampling technique was used to select 655study participants.
      A standardized questionnaire adapted from The World Health Organization's (WHO)
      STEP tool was used to collect the data. In this study, HTN was defined as mean
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 140/90 mmHg
      and above, and patients on regular drug therapy for H. Data were entered into EPI
      Info 3.5.2 and analyzed by SPSS version 20. Binary logistic regression model was
      used to identify associated factors. Odds ratio with 95 % CI was computed to
      assess the strength of the association and significant level. RESULT: The
      prevalence of hypertension was found to be 27.3 % (95 % CI 23.3 - 31 %). Civil
      servants of age 48 years and above [AOR = 5.88, 95 % CI: 2.36-14.67], age 38-47
      years [AOR = 2.80, 95 % CI: 1.18-6.60] and age 28-37 years [AOR = 2.35, 95 % CI:
      1.00-5.56]) were more likely to be hypertensive. Similarly, ever cigarette
      smoking [AOR =2.34(1.31-4.17), family history of hypertension [AOR = 3.26, 95 %
      CI 1.96-5.40], self-reported Diabetes Mellitus (DM) [AOR = 13.56, 95 % CI: 6.91
      26.6], and body mass index (BMI > 25 kg/m(2)) [AOR = 7.36, 95 % CI: 2.36-14.67]
      were found to be significantly associated with hypertension. CONCLUSION: The
      prevalence of hypertension among federal ministry civil servants was found to be
      high; which is an indication for institution based hypertension-screening
      programs especially focusing on those aged 28 years and above, obese, DM patients
      and cigarette smokers.

PMID- 26197713
TI  - [Hemochromatosis].
AB  - Hereditary hemochromatosis is a frequent autosomal recessive iron storage disease
      in northern and western Europe. The classical clinical triad of liver cirrhosis,
      hyperpigmentation and diabetes is nowadays rare, most probably because of early
      recognition. The homozygous C282Y mutation in the HFE gene is responsible for
      most cases of hereditary hemochromatosis, although other much rarer mutations in
      other genes have been recently identified. Progressive iron overload not only
      causes liver cirrhosis but also triggers development of a characteristic
      arthropathy. Bony swelling with intermittent arthritis of the second and third
      metacarpophalangeal joints is typical as well as occurrence of chondrocalcinosis
      in wrists and knee joints. The therapy of choice is excess iron removal by
      phlebotomy. Treatment usually prevents or even reverses liver damage but does not
      alter the course of hemochromatosis arthropathy. 

PMID- 26197714
TI  - Oxalate secretion by ectomycorrhizal Paxillus involutus is mineral-specific and
      controls calcium weathering from minerals.
AB  - Trees and their associated rhizosphere organisms play a major role in mineral
      weathering driving calcium fluxes from the continents to the oceans that
      ultimately control long-term atmospheric CO2 and climate through the geochemical
      carbon cycle. Photosynthate allocation to tree roots and their mycorrhizal fungi
      is hypothesized to fuel the active secretion of protons and organic chelators
      that enhance calcium dissolution at fungal-mineral interfaces. This was tested
      using (14)CO2 supplied to shoots of Pinus sylvestris ectomycorrhizal with the
      widespread fungus Paxillus involutus in monoxenic microcosms, revealing
      preferential allocation by the fungus of plant photoassimilate to weather grains
      of limestone and silicates each with a combined calcium and magnesium content of
      over 10 wt.%. Hyphae had acidic surfaces and linear accumulation of weathered
      calcium with secreted oxalate, increasing significantly in sequence: quartz,
      granite < basalt, olivine, limestone < gabbro. These findings confirmed the role
      of mineral-specific oxalate exudation in ectomycorrhizal weathering to dissolve
      calcium bearing minerals, thus contributing to the geochemical carbon cycle.

PMID- 26197715
TI  - Usefulness of Fluorescent Probe Prodan To Gain Insight into the Polarity of Plant
      Cuticles.
AB  - Plant cuticle is a complex mixture of hydrophobic components that controls the
      uptake of pesticides by plants. Although the transport of lipophilic molecules
      across the cuticle has been intensively studied, development of tools to measure
      the cuticle polarity has received little attention. We developed a rapid and
      simple analytical method to evaluate the polarity of cuticles in situ. This
      method uses Prodan, 6-propionyl-2-(dimethylaminonaphthalene), a medium-sensitive
      fluorescent probe. Tests on model surfaces with varied polarity (i.e., wax
      paraffin, polyethylene, C18) were carried out to test the feasibility of the
      measurement and to optimize the application of Prodan. Moreover, on the basis of
      the Kamlet-Taft solvatochromic comparison method, a relationship between the
      emission characteristics of Prodan and the number of carbon atoms in primary
      alcohols mimicking the solid medium was established. After optimization, the
      method was validated on three natural plant cuticles (leaf of Zamiifolia, skin of
      green pepper, and skin of white grape). 

PMID- 26197716
TI  - Angiotensin II promotes an osteoblast-like phenotype in porcine aortic valve
      myofibroblasts.
AB  - OBJECTIVES: The mechanisms for pathogenesis of cardiac valve calcification were
      explored by studying the regulation of the Wnt signaling pathway during the
      transformation from cardiac valvular myofibroblasts to osteoblast-like phenotype.
      METHODS: Studies were carried on primary cultured porcine aortic valvular
      myofibroblasts. The cells were randomly divided into four groups and treated with
      angiotensin II (Ang II) according to the following: Ang II (10(-6) mol/l),
      Valsartan (Val) (10(-5) mol/l), Ang II plus Val (Ang II 10(-6) mol/l + Val 10(-5)
      mol/l) or mock treated as the control. Protein expression of Bone morphogenetic
      protein 2 (BMP2), Alkaline phosphatase (ALP), and Wnt pathway components, Wnt3a
      and beta-catenin, was investigated to assess the activation of the Wnt signaling
      pathway and determine whether cells undergo the transformation to osteoblast-like
      phenotype. RESULT: Ang II treatment of myofibroblasts led to significant up
      regulation of alpha-SMA expression and activation of the cells. Neither the BMP2
      or ALP proteins, nor the mRNA was detectable in the control group or the Val
      treated group; however, there was a significant increase in Ang II-treated group
      (P < 0.01). The Wnt/beta-catenin signaling ligand, Wnt3a, was not expressed in
      the control or Val-treated groups, whereas in Ang II-treated cells, both Wnt3a
      and beta-catenin gene expression were enhanced (P < 0.01).The effect of Ang II
      can be inhibited by the addition of Val (P < 0.05). CONCLUSION: Ang II might act
      on the Ang II receptor on valvular interstitial cells (VICs) and lead to
      activation of the Wnt/beta-catenin pathway and hence cause the activation,
      differentiation and proliferation of myofibroblasts, and finally, osteoblast-like
      phenotype transformation, leading to calcification of heart valves.

PMID- 26197717
TI  - Sixteen weeks of resistance training decrease plasma heat shock protein 72
      (eHSP72) and increase muscle mass without affecting high sensitivity inflammatory
      markers' levels in sarcopenic men.
AB  - BACKGROUND: Sarcopenia has been associated with increased systemic inflammation
      and risk of physical disability in older adults. Recently, extracellular heat
      shock protein 72 (eHSP72) was proposed as a biomarker of sarcopenia but its
      response to interventions designed to increase muscle mass has never been
      evaluated. AIMS: The present study was designed to (1) assess eHSP72 levels
      following resistance training and, (2) determine whether changes in eHSP72
      correlate to changes in muscle mass and inflammatory markers. METHODS: A total of
      26 sarcopenic men participated in a 16-week resistance training program. The
      following variables were measured pre-post-intervention: plasma HSP72, serum high
      sensitivity (hs) inflammatory markers: interleukin-6 (hsIL-6), C-reactive protein
      (hsCRP), and tumor necrosis factor alpha (hsTNF-alpha), lean body mass (LBM) and
      appendicular muscle mass index (appMMI). RESULTS: eHSP72 was detected in 47 % of
      our participants and its level significantly decreased (P = 0.04) after the
      intervention, with a concomitant increase in several LBM variables and appMMI
      (all P < 0.035). Serum hsIL-6, hsCRP and hsTNF-alpha changes did not reach
      significance. Baseline hsIL-6 and hsCRP levels were negatively correlated with
      several LBM variables but solely baseline hsIL-6 was associated with changes in
      appLBM. No correlations were found between changes in measured variables.
      DISCUSSION: Attenuation of eHSP72 following resistance training in parallel with
      increase in LBM variables showed a concordance between the evolution of this
      biomarker and a clinical outcome relevant to sarcopenia. CONCLUSION:
      Nevertheless, the low bloodstream detection rate of eHSP72 in a sarcopenic
      otherwise healthy population might limit its use in clinical settings for now.

PMID- 26197718
TI  - Impaired healing of fragility fractures in type 2 diabetes: clinical and
      radiographic assessments and serum cytokine levels.
AB  - BACKGROUND: Diabetes induces bone alterations accompanied by altered cytokine
      expression patterns. These alterations lead to modified fracture healing,
      contributing to musculoskeletal fragility in the elderly. AIMS: We evaluated the
      inflammatory immune response in diabetic patients during fracture healing
      relative to clinical and radiographic assessments. METHODS: Fifty patients of
      both sexes with fragility fractures were studied: 30 diabetics (group A, mean age
      73.4 +/- 11.2 years) and 20 normoglycemic controls (group B, mean age 75.1 +/-
      16.9 years). Two subgroups comprised those with hip or wrist fragility fractures
      (25 and 16 patients, respectively). We evaluated serum concentrations of tumor
      necrosis factor alpha, interleukins 4 and 8, monocyte chemotactic protein-1 (MCP
      1), vascular endothelial growth factor, and epidermal growth factor (EGF) before
      and at 4 and 8 weeks after surgery. We also determined the Radiographic Union
      Score for Hips and the Radius Union Scoring System score and applied the Physical
      Activity Scale for the Elderly test at the same time points. Each patient
      underwent bone densitometry. RESULTS: MCP-1 and EGF levels were higher in group A
      than in group B at 4 weeks after surgery (p > 0.05). Radiographic evaluation
      showed lower scores in group A (p < 0.05). The main difference between the groups
      was evident 4 weeks after surgery. Changes in the serum concentrations of
      chemotactic and angiogenic factors could explain the radiographically proved
      impaired fracture healing in diabetic patients. CONCLUSIONS: Fragility fracture
      healing is impaired in diabetic patients. Radiographic and molecular patterns
      confirmed that the most compromised fracture-healing phase is at 4 weeks after
      surgery, during callus mineralization.

PMID- 26197719
TI  - Sarcopenia: a histological and immunohistochemical study on age-related muscle
      impairment.
AB  - BACKGROUND: Sarcopenia and osteoporosis increase the risk of bone fracture in the
      elderly due to the loss of muscle mass and the decrease in bone mineral density.
      Myostatin and Bone Morphogenetic Proteins (BMPs) are important molecules involved
      in muscle mass homeostasis. AIM: In this study, we investigated the role of BMP4
      and myostatin in the pathophysiogenesis of sarcopenia related to osteoporosis and
      osteoarthritis. METHODS: Muscle atrophy, BMP4 and myostatin expression were
      evaluated in 27 biopsies of osteoarthritic (OA) women and 27 biopsies from
      osteoporotic (OP) group by immunohistochemical reaction. Muscle stem cell niches
      were investigated by transmission electron microscopy analysis. RESULTS:
      Myostatin and BMP4 expression was evaluated by counting the number of positive
      fibers on 25 high-power field. We found that OA muscle biopsies showed a
      significantly higher number of BMP4-positive fibers (37.35 +/- 5.63) as compared
      with muscle of OP patients (9.60 +/- 1.57). Unlike BMP4 expression, the number of
      myostatin-positive fibers in OP patients (33.95 +/- 4.10) was significantly
      higher compared to OA group (13.86 +/- 1.68). The ultrastructural analysis of
      BMP4-positive tissues displayed the presence of a high rate of satellite cells
      both single or as syncytium giving proof of muscle regeneration capability.
      DISCUSSION: Our results indicated that sarcopenia and osteoporosis shared an
      impairment of metabolic activity. Conversely, the molecular mechanisms of OA seem
      to inhibit the onset of an age-related sarcopenia. CONCLUSION: The
      characterization of molecular mechanisms underlying the bone-muscle crosstalk
      could open new therapeutic perspectives in elderly diseases.

PMID- 26197720
TI  - Influence of psychological factors on acute exacerbation of tension-type
      headache: Investigation by ecological momentary assessment.
AB  - OBJECTIVE: In this study, we investigated whether psychological factors were
      associated with subsequent acute exacerbation of tension-type headache (TTH) in a
      prospective and ecologically valid manner with computerized ecological momentary
      assessment. METHODS: Eighteen women and five men with TTH wore watch-type
      computers that acted as an electronic diary for 1week. The subjects recorded
      momentary headache intensity, psychological stress, anxiety, and depressive mood
      with a visual analog scale of 0-100 approximately every 6h as well as when waking
      up, when going to bed, and at acute headache exacerbations. Multilevel logistic
      regression analysis with acute headache exacerbation occurrence as the outcome
      was conducted. Person-mean centering was applied to psychological factors to
      disaggregate between- and within-individual association. RESULTS: Momentary
      psychological stress was associated with subsequent increase in headache
      exacerbation within 3h [Odds Ratio (95% CI)=1.32 (1.07, 1.64) for 10-point
      increments] while the individual mean of psychological stress was not.
      CONCLUSION: These results support the possibility that psychological stress could
      trigger acute exacerbations of TTH.

PMID- 26197721
TI  - Effects of plyometric training on maximal-intensity exercise and endurance in
      male and female soccer players.
AB  - In a randomised controlled trial design, effects of 6 weeks of plyometric
      training on maximal-intensity exercise and endurance performance were compared in
      male and female soccer players. Young (age 21.1 +/- 2.7 years) players with
      similar training load and competitive background were assigned to training
      (women, n = 19; men, n = 21) and control (women, n = 19; men, n = 21) groups.
      Players were evaluated for lower- and upper-body maximal-intensity exercise, 30 m
      sprint, change of direction speed and endurance performance before and after 6
      weeks of training. After intervention, the control groups did not change, whereas
      both training groups improved jumps (effect size (ES) = 0.35-1.76), throwing (ES
      = 0.62-0.78), sprint (ES = 0.86-1.44), change of direction speed (ES = 0.46-0.85)
      and endurance performance (ES = 0.42-0.62). There were no differences in
      performance improvements between the plyometric training groups. Both plyometric
      groups improved more in all performance tests than the controls. The results
      suggest that adaptations to plyometric training do not differ between men and
      women. 

PMID- 26197722
TI  - Evaluation of the HIV lay counselling and testing profession in South Africa.
AB  - BACKGROUND: With the launch of the national HIV Counselling and Testing (HCT)
      campaign in South Africa (SA), lay HIV counsellors, who had been trained in blood
      withdrawal, have taken up the role of HIV testing. This study evaluated the
      experiences, training, motivation, support, supervision, and workload of HIV lay
      counsellors and testers in South Africa. The aim was to identify gaps in their
      resources, training, supervision, motivation, and workload related to HCT
      services. In addition it explored their experiences with providing HIV testing
      under the task shifting context. METHODS: The study was conducted in eight of
      South Africa's nine provinces. 32 lay counsellors were recruited from 67 HCT
      sites, and were interviewed using two questionnaires that included structured and
      semi-structured questions. One questionnaire focused on their role as HIV
      counsellors and the other on their role as HIV testers. RESULTS: Ninety-seven
      percent of counsellors reported that they have received training in counselling
      and testing. Many rated their training as more than adequate or adequate, with
      15.6% rating it as not adequate. Respondents reported a lack of standardised
      counselling and testing training, and revealed gaps in counselling skills for
      specific groups such as discordant couples, homosexuals, older clients and
      children. They indicated health system barriers, including inadequate designated
      space for counselling, which compromises privacy and confidentiality. Lay
      counsellors carry the burden of counselling and testing nationally, and have
      other tasks such as administration and auxiliary duties due to staff shortages.
      CONCLUSIONS: This study demonstrates that HCT counselling and testing services in
      South Africa are mainly performed by lay counsellors and testers. They are
      challenged by inadequate work space, limited counselling skills for specific
      groups, a lack of standardised training policies and considerable administrative
      and auxiliary duties. To improve HCT services, there needs to be training needs
      with a standardised curriculum and refresher courses, for HIV counselling and
      testing, specifically for specific elderly clients, discordant couples,
      homosexuals and children. The Department of Health should formally integrate lay
      counsellors into the health care system with proper allocation of tasks under the
      task shifting policy.

PMID- 26197724
TI  - Fine mapping analysis of HLA-DP/DQ gene clusters on chromosome 6 reveals multiple
      susceptibility loci for HBV infection.
AB  - Recent genome-wide association studies have revealed the HLA region on chromosome
      6p21 as a susceptibility locus for hepatitis B virus (HBV) infection, a finding
      subsequently replicated in independent samples. However, only limited single
      nucleotide polymorphisms (SNPs) were analyzed in most of these studies, and it
      remains to be determined which SNPs contribute to the detected association. After
      genotyping 140 SNPs within this genomic region in a total of 1657 HBV-positive
      patients and 1456 HBV-negative controls, we conducted a series of genetic
      epidemiological and bioinformatics analysis, including individual SNP-based
      association analysis, haplotype-based association analysis, and conditional
      analysis. We identified 76 SNPs and 5 LD blocks in HLA-DP/DQ clusters that are
      significantly associated with HBV infection, with the smallest P value being 3.88
      * 10(-18) for rs9277535 in HLA-DPB1. With conditional analysis, we further
      revealed that the genes contributing to the effects of variants in HLA-DP/DQ on
      infection are independent of each other, and the LD block 5 in the 3'-UTR region
      of HLA-DPB1 had a predominant effect in the association of HLA-DP with HBV
      infection. We also found that the SNPs in the 3'-UTR region of HLA-DPB1 were
      significant between the subgroups of inactive HBV carrier, chronic hepatitis B,
      or hepatic cirrhosis from the case group and the spontaneous HBV-clearance
      subgroup from the control group. Finally, we did further association analysis of
      SNPs in this region with different subgroups from the case group, which revealed
      no association of these SNPs with the progression of HBV-related diseases. In
      sum, we showed, for the first time, that the HLA-DP/DQ clusters contribute
      independently to HBV infection, and the 3'-UTR region of HLA-DPB1 represents an
      important functional region involved in HBV infection.

PMID- 26197725
TI  - Long-term effects of prevention and treatment on youth antisocial behavior: A
      meta-analysis.
AB  - Youth antisocial behavior exacts a tremendous toll on society and often persists
      into adulthood. Although researchers have identified a number of psychosocial
      interventions that prevent or reduce youth antisocial behavior in the short term,
      evidence of long-term intervention benefits has only recently become available.
      In addition, research on such interventions spans two substantial but largely
      separate bodies of literature: prevention and therapy. The present study used
      meta-analysis to integrate research on the long-term effects of preventive and
      therapeutic interventions for youth antisocial behavior and examined potential
      moderators of these effects. Results from 66 intervention trials (i.e., 34
      prevention, 32 therapy) indicated that a broad range of youth psychosocial
      interventions demonstrated modest effects on antisocial behavior (mean d=0.31,
      95% confidence interval=0.23-0.39) for at least one year beyond the end of
      interventions relative to control conditions. Among other findings, moderator
      analyses revealed that inclusion of a peer group intervention component was
      associated with reduced intervention effects for samples consisting predominantly
      of boys or older youths. The results of this study have important implications
      for service providers, administrators, and policymakers involved in the
      implementation of preventive and therapeutic interventions targeting youth
      antisocial behavior. 

PMID- 26197727
TI  - Phonatory aerodynamics in connected speech.
AB  - OBJECTIVES/HYPOTHESIS: 1) Present phonatory aerodynamic data for healthy controls
      (HCs) in connected speech; 2) contrast these findings between HCs and patients
      with nontreated unilateral vocal fold paralysis (UVFP); 3) present pre- and post
      vocal fold augmentation outcomes for patients with UVFP; 4) contrast data from
      patients with post-operative laryngeal augmentation to HCs. STUDY DESIGN:
      Retrospective, single-blinded. METHODS: For phase I, 20 HC participants were
      recruited. For phase II, 20 patients with UVFP were age- and gender-matched to
      the 20 HC participants used in phase I. For phase III, 20 patients with UVFP
      represented a pre- and posttreatment cohort. For phase IV, 20 of the HC
      participants from phase I and 20 of the postoperative UVFP patients from phase
      III were used for direct comparison. Aerodynamic measures captured from a sample
      of the Rainbow Passage included: number of breaths, mean phonatory airflow rate,
      total duration of passage, inspiratory airflow duration, and expiratory airflow
      duration. The VHI-10 was also obtained pre- and postoperative laryngeal
      augmentation. RESULTS: All phonatory aerodynamic measures were significantly
      increased in patients with preoperative UVFP than the HC group. Patients with
      laryngeal augmentation took significantly less breaths, had less mean phonatory
      airflow rate during voicing, and had shorter inspiratory airflow duration than
      the preoperative UVFP group. None of the postoperative measures returned to HC
      values. Significant improvement in the Voice Handicap Index-10 scores
      postlaryngeal augmentation was also found. CONCLUSIONS: Methodology described in
      this study improves upon existing aerodynamic voice assessment by capturing
      characteristics germane to UVFP patient complaints and measuring change before
      and after laryngeal augmentation in connected speech. LEVEL OF EVIDENCE: 4.

PMID- 26197726
TI  - Network destabilization and transition in depression: New methods for studying
      the dynamics of therapeutic change.
AB  - The science of dynamic systems is the study of pattern formation and system
      change. Dynamic systems theory can provide a useful framework for understanding
      the chronicity of depression and its treatment. We propose a working model of
      therapeutic change with potential to organize findings from psychopathology and
      treatment research, suggest new ways to study change, facilitate comparisons
      across studies, and stimulate treatment innovation. We describe a treatment for
      depression that we developed to apply principles from dynamic systems theory and
      then present a program of research to examine the utility of this application.
      Recent methodological and technological developments are also discussed to
      further advance the search for mechanisms of therapeutic change. 

PMID- 26197728
TI  - GP responses to price regulation: evidence from a French nationwide reform.
AB  - This paper uses a French reform to evaluate the impacts of overbilling
      restrictions on general practitioner (GP) care provision, fees and incomes. Since
      1990, this reform has introduced conditions self-employed GPs must fulfil to be
      permitted to bill freely. We exploit 2005 and 2008 public health insurance
      administrative data on GP activity and fees. We use fuzzy regression
      discontinuity techniques to estimate local causal impacts for GPs who established
      practices in 1990 and who were constrained by the new regulation to charge
      regulated prices (compliers). We find that those GPs practices to income effects.
      In the regulated fee regime, GPs face prices lower by 42% and provide 50% more
      care than they would do in the unregulated fee regime. Male care provision
      increasing reaction is larger than the female one, which results in a higher male
      labour income in the regulated fee regime than with unregulated fees, whereas it
      is the opposite for women. With regulated fees, GPs limit side-salaried
      activities, use more lump-sum payment schemes and occupy more often gatekeeper
      positions.

PMID- 26197729
TI  - Quality of life after suprapubic catheter placement in patients with neurogenic
      bladder conditions.
AB  - AIMS: To evaluate quality of life in patients with neurogenic bladder (NGB)
      conditions who have elected to undergo suprapubic catheterization (SPC), as well
      as assess adverse events (AEs) related to the procedure. METHODS: This is a
      retrospective review from a database of NGB patients from 1/1/2003 to 6/30/2013.
      Patients who underwent SPC placement were invited to complete a validated, single
      item Patient Global Impression of Improvement (PGI-I) questionnaire. Success or
      positive response was defined as 1 or 2 on a scale of 1-7. All patients were
      included in the assessment of AEs. RESULTS: Of the 128 patients who underwent
      SPC, 89 patients (54 female, 35 male) met inclusion criteria. Response rate to
      the PGI-I questionnaire was 65.2% (58/89). Mean age at the time of SPC placement
      was 54.4 years (+/- 14.4). The mean time from SPC placement to PGI-I
      questionnaire was 48.3 months (Range 4.4-128.4). Overall, success was seen in
      49/58 patients (84.5%). Only 5.2% (3/58) patients reported a negative PGI-I
      (score 5/7). There was an 18.8% rate of short term complications, with the
      majority of these being classified as Clavien I. There was one Clavien IIIb
      complication (0.8%), which consisted of a small bowel perforation. CONCLUSIONS:
      SPC is an effective bladder management in carefully selected NGB patients who
      have failed other options. Over 80% considered the SPC to have improved their
      urological quality of life with a mean time to questionnaire of 4 years. Severe
      AEs are rare, though can be particularly serious in this group of neurologically
      impaired patients. Neurourol. Urodynam. 35:831-835, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26197730
TI  - Comparison of three protein extraction procedures from toxic and non-toxic
      dinoflagellates for proteomics analysis.
AB  - Three methods for extraction and preparation of high-quality proteins from both
      toxic and non-toxic dinoflagellates for proteomics analysis, including Trizol
      method, Lysis method and Tris method, were compared with the subsequent protein
      separation profiles using 2-D differential gel electrophoresis (2-D DIGE),
      Coomassie Blue and silver staining. These methods showed suitability for proteins
      with different pIs and molecular weights. Tris method was better for low
      molecular weight and low pI protein isolation; whereas both Lysis and Trizol
      method were better for high-molecular weight and high pI protein purification.
      Trizol method showed good results with Alexandrium species and Gynodinium
      species, and the background in gel was much clearer than the other two methods.
      At the same time, only Lysis method caused breaking down of the target proteins.
      On the other hand, Trizol method obtained higher concentration of ribulose-1,5
      bisphosphate carboxylase/oxygenase proteins by Western-blotting, while Tris
      method was the best for peridinin-chlorophyll-protein complexes protein and T1
      protein preparation. DIGE was better than Coomassie Blue and silver staining,
      except for some limitations, such as the high cost of the dyes, relatively short
      shelf life and the requirements for extensive and special image capturing
      equipment. Some proteins related to PSTs synthesis in dinoflagellates are
      hydrophobic with high molecular weight or binding on membranes and Trizol method
      performed better than Tris method for these proteins. The Trizol method and 2-D
      DIGE were effective combination for proteomics investigations of dinoflagellates.
      This procedure allows reliable and high recovery efficiency of proteins from
      dinoflagellates for better understanding on their occurrence and toxin-production
      for physiological and biochemical information. 

PMID- 26197731
TI  - Cultivation-dependent analysis of the microbial diversity associated with the
      seagrass meadows in Xincun Bay, South China Sea.
AB  - Microbial communities have largely existed in the seagrass meadows. A total of
      496 strains of the bacteria in the seagrass meadows, which belonged to 50 genera,
      were obtained by the plate cultivation method from three sites of Xincun Bay,
      South China Sea. The results showed that Bacillales and Vibrionales accounted for
      the highest proportions of organisms in all communities. The diversity of the
      bacteria in the sediment was higher than that associated with seagrass. Thalassia
      hemperichii possessed the highest abundance of bacteria, followed by Enhalus
      acoroides and Cymodocea rotundata. Robust seasonal dynamics in microbial
      community composition were also observed. It was found that microbial activities
      were closely tied to the growth stage of the seagrass. The microbial distribution
      was the lowest in site 3. The abundance of the bacteria was linked to the
      interactions between bacteria and plants, the condition of plant and even the
      coastal water quality and the nutrition level in the sediment.

PMID- 26197732
TI  - Human-Centered Design as an Approach for Place-Based Innovation in Public Health:
      A Case Study from Oakland, California.
AB  - PURPOSE: This case study provides a high-level overview of the human-centered
      design (HCD) or "design thinking" process and its relevance to public health.
      DESCRIPTION: The Best Babies Zone (BBZ) initiative is a multi-year project aimed
      at reducing inequities in infant mortality rates. In 2012, BBZ launched pilot
      programs in three US cities: Cincinnati, Ohio; New Orleans, Louisiana; and
      Oakland, California. The Alameda County Public Health Department (ACPHD), the
      lead for the Oakland BBZ site, identified HCD as a promising approach for
      addressing the social and economic conditions that are important drivers of
      health inequities. HCD is a process for creating innovative products, services,
      and strategies that prioritizes the needs of the intended population. ACPHD
      partnered with the Gobee Group (a social innovation design consultancy) to
      develop the Design Sprint. The Design Sprint was a 12-week pilot in which 14
      professionals from nine organizations used the HCD process to develop concepts
      for stimulating a vibrant local economy in the Oakland Best Babies Zone.
      ASSESSMENT: Thirty- to sixty-minute semi-structured interviews were conducted
      with all 14 individuals involved in the Design Sprint. With the exception of one
      interview, the interviews were audio-recorded, transcribed, and inductively coded
      to identify themes. CONCLUSION: Our experience suggests that HCD can: enhance
      community engagement; expedite the timeframe for challenge identification,
      program design, and implementation; and create innovative programs that address
      complex challenges.

PMID- 26197733
TI  - Alcohol Use During Pregnancy in a South African Community: Reconciling Knowledge,
      Norms, and Personal Experience.
AB  - OBJECTIVES: Due to high rates of fetal alcohol spectrum disorder (FASD) in South
      Africa, reducing alcohol use during pregnancy is a pressing public health
      priority. The aim of this study was to qualitatively explore knowledge and
      attitudes about maternal alcohol consumption among women who reported alcohol use
      during pregnancy. METHODS: The study was conducted in Cape Town, South Africa.
      Participants were pregnant or within 1 year postpartum and self-reported alcohol
      use during pregnancy. In-depth interviews explored personal experiences with
      drinking during pregnancy, community norms and attitudes towards maternal
      drinking, and knowledge about FASD. Transcripts were analyzed using a content
      analytic approach, including narrative memos and data display matrices. RESULTS:
      Interviews revealed competing attitudes. Women received anti-drinking messages
      from several sources, but these sources were not highly valued and the messages
      often contradicted social norms. Women were largely unfamiliar with FASD, and
      their knowledge of impacts of fetal alcohol exposure was often inaccurate.
      Participants' personal experiences influenced their attitudes about the effects
      of alcohol during pregnancy, which led to internalization of misinformation. The
      data revealed a moral conflict that confronted women in this setting, leaving
      women feeling judged, ambivalent, or defensive about their behaviors, and
      ultimately creating uncertainty about their alcohol use behaviors. CONCLUSIONS:
      Data revealed the need to deliver accurate information about the harms of fetal
      alcohol exposure through sources perceived as trusted and reliable. Individual
      level interventions to help women reconcile competing attitudes and identify
      motivations for reducing alcohol use during pregnancy would be beneficial.

PMID- 26197735
TI  - Knowledge-based iterative model reconstruction (IMR) algorithm in ultralow-dose
      CT for evaluation of urolithiasis: evaluation of radiation dose reduction, image
      quality, and diagnostic performance.
AB  - PURPOSE: To evaluate the efficacy of a knowledge-based iterative model
      reconstruction (IMR) algorithm for reducing image noise in ultralow-dose (ULD) CT
      for urolithiasis. MATERIALS AND METHODS: A total of 103 patients diagnosed with
      urinary stones (n = 276) were enrolled. Regular dose (RD) scans (120 kV and 150
      mAs, maximal tube current in dose modulation) were reconstructed using filtered
      back-projection (FBP, RD-FBP), and ULD scans (100 kV and 20 mAs, fixed tube
      current) were reconstructed with FBP (ULD-FBP), statistical iterative
      reconstruction (IR; ULD-iDose), and a knowledge-based IMR algorithm (ULD-IMR).
      Prospective interpretations of the two scans were performed with respect to
      radiation dose, objective image noise, and subjective assessment. The subjective
      assessment was also evaluated with regard to each patient's body mass index (BMI,
      < 25 or >= 25 kg/m(2)). Using RD CT (RD-FBP) as the reference standard, two
      reviewers assessed the diagnostic performance and inter-observer agreement for
      ULD-IMR. RESULT: The average effective doses with RD CT and ULD CT were 8.31 and
      0.68 mSv, respectively, and the average radiation dose reduction rate was 91.82%
      (p < 0.01). The lowest objective image noise was observed with ULD-IMR (p <
      0.01). Subjective assessment in ULD-IMR was comparable to that of RD-FBP,
      although RD-FBP remained statistically superior. For BMI, there was a
      statistically significant difference in subjective image quality between the
      normal (4.7 +/- 0.54) and overweight or obese groups (4.2 +/- 0.5) (p < 0.05).
      The ULD-IMR showed a greater than 75% concordant rate in overall stones and 100%
      in ureter stones larger than 3 mm. However, for stones <3 mm, neither reviewer
      had a good detection rate (45.5% and 56.9% for the general and genitourinary
      radiologist, respectively). Inter-observer agreement was almost perfect (kappa =
      0.82). CONCLUSION: Despite a significant radiation dose reduction, ULD-IMR images
      were comparable in image quality and noise to RD-FBP images. Furthermore, the
      diagnostic performance of the ULD non-enhanced CT protocol was comparable to that
      of the RD scan for diagnosing urinary stones larger than 3 mm.

PMID- 26197736
TI  - [Progress of Regional Therapy for Hepatocellular Carcinoma].
AB  - There are 2 types of regional therapy for hepatocellular carcinoma(HCC). One is
      transarterial therapy based on the dual supply of hepatic blood flow and
      characteristics of hypervascular tumors, and the other is local puncture or
      ablation therapy using a needle or an electric pole. The latter type of therapy
      is based on the macroscopic form of HCC, which is localized and nodular. With
      regard to transarterial therapies, hepatic arterial infusion(HA), ligation of
      hepatic arteries(dearterialization), and transarterial
      chemoembolization(TACE)have been developed and improved. At present, TACE with
      Lipiodol(Lip-TACE) is a first-line therapy for locally advanced HCC. Moreover,
      with regard to local puncture or ablation therapies, percutaneous ethanol
      injection(PEI)and microwave coagulation therapy(MCT)-both of which originated in
      Japan-as well as radiofrequency ablation(RFA)have been developed and improved. At
      present, the first-line local ablation therapy for relatively earlystage HCC(3 cm
      or less in diameter and 3 or less tumors)is RFA. A RCT is underway to compare the
      long-term prognosis of patients with HCC between hepatic resection and RFA. 

PMID- 26197737
TI  - [Rehabilitation for Motor Dysfunction in Patients with Cancer].
AB  - Advancements in cancer treatment have led to an increase in the 5-year survival
      rate to>50%for various cancers. However, cancer remains a serious disease that
      affects the patients' life. Cancer progression or invasive treatments may cause
      various disabilities in patients. For example, functional impairment is a typical
      problem leading to impaired activities of daily living and quality of life,
      extended hospital stay, and increased burden for the family. Optimal
      rehabilitation is needed to improve the motor function and activity of these
      patients. The number of reports that describe the effect of cancer rehabilitation
      has increased in recent years. On the basis of these reports, the Guideline
      Committee of the Japanese Association of Rehabilitation Medicine has published
      clinical guidelines for cancer rehabilitation in 2013. Providing a rehabilitation
      program, however, is sometimes problematic because the general condition of
      cancer patients is sometimes complicated by a fluctuating clinical course. To
      create a rehabilitation program for cancer patients, various factors should be
      taken into consideration, such as the severity of the dysfunction, life
      expectancy, and risk of complications. Among the potential complications, bone
      metastasis is the most serious problem. As the risk of skeletal-related events is
      increased by exercise or improvement in the activities of daily living, the
      merits and risks of rehabilitation need to be evaluated. To improve the quality
      of cancer rehabilitation, highly specialized education for physicians and
      therapists is needed. 

PMID- 26197738
TI  - [Swallowing and Voice Disorders in Cancer Patients].
AB  - Dysphagia sometimes occurs in patients with head and neck cancer, particularly in
      those undergoing surgery and radiotherapy for lingual, pharyngeal, and laryngeal
      cancer. It also occurs in patients with esophageal cancer and brain tumor.
      Patients who undergo glossectomy usually show impairment of the oral phase of
      swallowing, whereas those with pharyngeal, laryngeal, and esophageal cancer show
      impairment of the pharyngeal phase of swallowing. Videofluoroscopic examination
      of swallowing provides important information necessary for rehabilitation of
      swallowing in these patients. Appropriate swallowing exercises and compensatory
      strategies can be decided based on the findings of the evaluation. Palatal
      augmentation prostheses are sometimes used for rehabilitation in patients
      undergoing glossectomy. Patients who undergo total laryngectomy or total
      pharyngolaryngoesophagectomy should receive speech therapy to enable them to use
      alaryngeal speech methods, including electrolarynx, esophageal speech, or speech
      via tracheoesophageal puncture. Regaining swallowing function and speech can
      improve a patient's emotional health and quality of life. Therefore, it is
      important to manage swallowing and voice disorders appropriately. 

PMID- 26197739
TI  - [Pulmonary Rehabilitation for Cancer Patients].
AB  - Dyspnea occurs in most cancer patients and is often associated with severe pain.
      Pulmonary rehabilitation has become increasingly important to improve ADL and QOL
      and to relieve pain that results from dyspnea. Although pulmonary rehabilitation
      is now provided mainly during the perioperative period, it has been recognized as
      an effective procedure for patients before, during, or after chemotherapy or
      radiotherapy. It is also useful for patients with advanced or terminal cancer.
      However, an evidence-based cancer rehabilitation procedure has to be established.

PMID- 26197740
TI  - [Cancer and Malnutrition].
AB  - A Japanese proverb says that a balanced diet leads to a healthy body. However,
      the relation between healthy life and nutrition has not been established
      precisely and quantitatively. Cancer cachexia, which is malnutrition in cancer
      patients, has been studied extensively. Appropriate nutrition support can prevent
      the progression of malnutrition in cancer patients and advance the tolerance for
      anticancer therapy. In refractory cachexia (terminally cancer patients), we will
      judge the necessity of reduction of nutrition support, what it is called "gear
      change", because the support is burden for the body. It is important to restrict
      the quantity of nutrition and to give medical treatment to retain bodily function
      in these patients.

PMID- 26197741
TI  - [Efficacy and Safety of the Selective Estrogen Receptor Down-Regulator
      "Fulvestrant" in Japanese Patients with Advanced, Recurrent, ER-Positive
      Postmenopausal Breast Cancer].
AB  - Fulvestrant is a novel endocrine therapy for breast cancer that exerts both anti
      estrogenic and down-regulatory effects by binding to and degrading estrogen
      receptors (ERs). In the present study, the safety and effectiveness of 500 mg
      fulvestrant in 69 patients with advanced, recurrent, ER-positive postmenopausal
      breast cancer were investigated retrospectively. Outcomes were favorable for
      fulvestrant. The objective response rate was 24.6%, the clinical benefit rate was
      49.2%, the median progression-free survival (PFS) was 203 days, and the median
      overall survival was 794 days. PFS tended to be longer in patients without a
      history of previous treatment or visceral metastasis. The main adverse events
      included injection site reactions and hot flushes; however, the majority of these
      events were mild to moderate. The present findings suggest that, among Japanese
      patients with advanced, recurrent, ER-positive postmenopausal breast cancer, 500
      mg fulvestrant is effective and safe in those without metastasis and a minimal
      history of receipt of previous treatment regimens.

PMID- 26197742
TI  - [Initial Evaluation of the Efficacy and Safety of Tablets Containing Trifluridine
      and Tipiracil Hydrochloride--Safety Measures Devised by a Multidisciplinary Team
      Including a Pharmaceutical Outpatient Clinic].
AB  - In May 2014, tablets containing both trifluridine and tipiracil hydrochloride
      (Lonsurf(r) tablets) were launched in Japan ahead of other countries, for the
      treatment of advanced/relapsed unresectable colorectal cancer. The benefits of
      these tablets in terms of a new therapeutic option have been demonstrated.
      However, the manufacturer has requested healthcare professionals to help develop
      safety measures for the appropriate and safe use of the tablets. In this study,
      we evaluated the efficacy and safety of the tablets in 16 patients who received
      the tablets at our hospital. Among the 4 evaluable patients, none achieved a
      complete or partial response. One patient (25.0%) had stable disease according to
      the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines outlined in
      the General Rules of the Study of Colorectal Cancer (The 8th Edition). Lonsurf(r)
      is considered to be a third-line (or later) treatment. Among the 16 cases
      studied, Lonsurf(r) was used as a third-, fourth-, and fifth-line treatment in 9,
      6, and 1 cases, respectively. Therefore, Grade 3 or worse toxicities were a
      potential concern. Despite a high incidence of Grade 3 or worse neutropenia (7 of
      the 16 patients [43.8%]), none of the patients were hospitalized due to
      neutropenia or other treatment-related adverse events. Pharmacists have made 126
      proposals to physicians regarding the use of Lonsurf(r), 121 (96.0%) of which
      have been adopted. All of the adverse reactions experienced by our patients were
      resolved after supportive therapy.

PMID- 26197743
TI  - [Nogitecan Hydrochloride Treatment for Patients with Recurrent Ovarian Cancer].
AB  - Nogitecan hydrochloride(topotecan)has shown efficacy in patients with recurrent
      ovarian cancer, but has not been used widely in Japan. We evaluated the efficacy
      and adverse effects of topotecan in 12 patients (median age, 62 years) treated
      for recurrent ovarian cancer between 2000 and 2013. Four patients had relapsed
      after primary treatment, and 8 had relapsed at least twice. Seven patients had
      been treated with more than 3 prior regimens. Initial treatment of the 12
      patients consisted of intravenous topotecan (1.0-1.4 mg/m2/day) for 5 consecutive
      days. Initial doses were based on previous chemotherapy and/ or renal function,
      with reduced doses administered to patients with severe adverse effects during
      prior courses of treatment. The 12 patients received a total of 54 courses of
      topotecan(range, 1-15 courses). Of these 12 patients, one achieved a partial
      response and 6 had stable disease. The median time to progression was 14.4 weeks.
      All 12 patients had grade 3-4 myelosuppression, while none had febrile
      neutropenia or severe non-hematologic toxicities. Patients who received higher
      doses or increased courses of chemotherapy had apparently more severe adverse
      events. These findings suggested that topotecan should be used as a second- or
      third-line treatment, rather than later, in patients with tumor recurrence, with
      its dose reduced according to the physical status of each patient. Such
      strategies may enhance both the efficacy and safety of topotecan in patients with
      recurrent ovarian cancer.

PMID- 26197744
TI  - [Evaluation of the Safety of a Generic Formulation of Cisplatin in Patients with
      Thoracic Malignancies].
AB  - Cisplatin (CDDP) is a key drug in the systemic treatment of various solid tumors.
      Brand-name CDDP may differ across generic formulations considering various
      clinical parameters. Therefore, in this study, we aimed to assess the safety of a
      generic CDDP formulation. To compare brand-name CDDP with a generic formulation,
      the incidence of adverse events, especially renal toxicity, was investigated in
      500 patients with thoracic malignancies who received chemotherapy with more than
      60 mg/m2 of either brand-name or generic CDDP. We compared the maximum serum
      creatinine (Cr) level after chemotherapy in the 2 groups. The correlation
      coefficients between the pretreatment Cr and the maximum Cr after CDDP
      administration did not differ between brand-name CDDP and generic CDDP (0.610 and
      0.644, respectively; p=0.528). Furthermore, the correlation coefficients did not
      differ in subgroup analysis according to sex or adjuvant therapy. The severity of
      adverse events was similar in the 2 groups. In conclusion, generic CDDP can
      safely be used as an alternative to brand-name CDDP in the clinical setting.

PMID- 26197745
TI  - A Study on Drug Interaction between Warfarin and Capecitabine with Special
      Reference to the Co-Administered Term or the Discontinuation Term of
      Capecitabine.
AB  - We used the prothrombin time international normalized ratio(PT-INR)to investigate
      the change in degree and term of warfarin following co-administration and after
      discontinuation of capecitabine. In this study, approximately 3 years of medical
      records of 7 patients receiving co-administration therapy of warfarin and
      capecitabine were obtained from 4 hospitals. We observed daily increases in PT
      INR values up to peak PT-INR levels following co-administration of warfarin and
      capecitabine. Interestingly, the peak PT-INR values of 4 of the patients remained
      remarkably high despite discontinuation of capecitabine. The peak PT-INR values
      for concomitant warfarin and capecitabine were attained after an average of 31.3
      days of usage. When compared with the average PT-INR values attained before co
      administration, the PT-INR values following co-administration significantly
      increased by 3 times (p<0.05). After discontinuation of capecitabine for an
      average of 15.1 days, i. e., for approximately 14 days, the PT-INR values
      returned to the PT-INR values attained prior to co-administration. These results
      suggest that capecitabine has influence on the anticoagulant effect of warfarin
      during not only the co-administered term but also the discontinuation term, and
      that this influence occasionally continues after discontinuation of capecitabine.
      These findings also suggest that a period of approximately 14 days after
      discontinuation is necessary for the interaction of capecitabine to dissipate and
      the PT-INR values to return the levels attained before receiving concomitant
      warfarin and capecitabine.

PMID- 26197746
TI  - [Development of a Drug Cost Calculation Tool for Breast Cancer Therapy].
AB  - Drug cost is considered an important factor in treatment compliance for cancer
      patients. However, it is difficult to calculate individual drug costs. We were
      previously unable to provide sufficient information on costs to cancer patients
      starting drug therapy. Therefore, we developed a tool, in the form of a
      spreadsheet, which calculates drug costs for breast cancer treatment. This
      software tool runs on every terminal for electronic medical charts in our
      hospital. To evaluate the tool, we created 10 fictional breast cancer patient
      sets. Five pharmacists calculated the drug costs for a single regimen using
      method A (without software) and method B (with software). The pharmacists then
      calculated the drug costs for 3 regimens in the same way. We compared the time
      taken to calculate costs using method A and method B. For the single regimen, the
      mean time for method B (22.6+/-6.9 s) was 6.4-times shorter than that for method
      A (145.2+/-28.3 s, p<0.0001). For the 3 regimens, the mean time for method B
      (35.5+/-5.0 s) was 8.9-times shorter than that for method A (315.8+/-43.1 s,
      p<0.0001). The differences observed were statistically significant. By using the
      software, we were able to shorten the calculation time for drug costs, and
      therefore, alleviate the burden on medical staff.

PMID- 26197747
TI  - [A Case of Pneumatosis Cystoides Intestinalis Secondary to Gefitinib Therapy for
      Lung Adenocarcinoma].
AB  - Pneumatosis cystoides intestinalis (PCI) is a relatively rare condition,
      characterized by subserosal or submucosal air within the bowel wall. Herein, we
      report a rare case of PCI secondary to treatment with an epidermal growth factor
      receptor-tyrosine kinase inhibitor (EGFR-TKI). A 71-year-old man, who had
      received gefitinib therapy for 2 years and 5 months for lung adenocarcinoma with
      metastases to the bones and brain, presented with abdominal pain, diarrhea, and
      vomiting. Computed tomography of the abdomen revealed intramural air in the small
      bowel, free air in the abdomen, and moderate ascites. A diagnosis of PCI was
      made, and the patient was managed conservatively by discontinuing gefitinib
      treatment, because his vital signs were stable and there was no sign of
      peritonitis. The patient's symptoms gradually improved, and follow-up CT after 1
      week revealed that the initial findings had almost completely resolved.
      Clinicians should note that treatment with gefitinib might cause PCI.

PMID- 26197748
TI  - [Clinical Efficacy of Alternate-Day S-1/Letrozole Combination Therapy for
      Advanced Breast Cancer with Gastric Metastasis--A Case Report].
AB  - We report a case of Stage IV breast cancer in a 62-year-old woman who responded
      well to alternate-day S-1/letrozole combination therapy. She was admitted to our
      hospital because of appetite loss and vomiting, and was diagnosed with invasive
      lobular carcinoma (ER+/HER2-) with gastric metastasis. After gastrointestinal
      stenting was performed, we initiated oral administration of S-1 (100 mg/body) and
      letrozole (2.5 mg) as systemic therapy. To reduce adverse effects, we
      administered S-1 on alternate days. Computed tomography and endoscopic
      examination revealed that the patient has been showing partial response since 1
      year after initiating treatment. Therefore, we conclude that alternate-day S
      1/letrozole combination therapy could be an effective and sustainable treatment
      for advanced ER-positive, HER2-negative breast cancer.

PMID- 26197749
TI  - [A Successfully Treated Case of Central Venous Catheter-Related Suppurative
      Thrombophlebitis of the Right Jugular Vein to the Superior Vena Cava Associated
      with Esophageal Cancer].
AB  - A 63 year-woman was diagnosed with esophageal cancer (Mt. T4N2M0, c-Stage IIIC)
      after full examination. She underwent chemotherapy with 5-FU+CDDP (FP) through a
      central venous line (CV). She developed a fever of more than 40 degrees C 15 days
      after the first course of chemotherapy. We removed the CV owing to suspicion of
      catheter-related bloodstream infection (CRBSI) and initiated treatment with
      antibiotics (CFPM). Even so, she experienced swelling from the right cervix to
      the precordium. We confirmed suppurative thrombophlebitis from the right jugular
      vein to the superior vena cava by CT and blood culture. After anti-coagulation
      therapy, venous thrombosis diminished and inflammation was cured. The patient
      continued to receive chemotherapy, underwent a bypass operation, and completed
      chemo-radiotherapy successfully while receiving anti-coagulation therapy.

PMID- 26197750
TI  - [Multidisciplinary Treatment for a Patient with Primary Malignant Melanoma
      Arising from the Stomach].
AB  - A 61-year-old woman was referred to our hospital with the complaint of severe
      dysphagia. Upper gastrointestinal endoscopy revealed an elevated tumor with an
      irregular surface located in the upper third of the stomach, and malignant
      melanoma was confirmed by biopsy specimens. Abdominal CT scan findings revealed
      that the tumor was invading the lateral segment of the liver and crus of the
      diaphragm. Total gastrectomy was combined with resection of the lateral segment
      of the liver and the crus of the diaphragm, and D2 lymphadenectomy and
      reconstruction by the Roux-en-Y method were carried out. Because of positive
      peritoneal washing cytology, monotherapy with dacarbazine, and combination
      therapy, including dacarbazine, nimustine hydrochloride, cisplatin, and tamoxifen
      citrate, were administered for treating the residual tumor. The patient died from
      peritoneal relapse 146 days after the initial surgery. Primary malignant melanoma
      arising from the stomach is reported as an extremely rare disease with a poor
      prognosis. In our case, multidisciplinary treatment including surgery and
      chemotherapy was insufficient to achieve long-term survival in a highly advanced
      malignant melanoma arising from the stomach. 

PMID- 26197751
TI  - [Two Patients with Recurrence of Hepatocellular Carcinoma after Liver Resection
      Who Achieved Long-Term Stable Disease with Small Doses of Sorafenib Therapy].
AB  - Case 1: A6 4-year-old man with hepatocellular carcinoma (HCC) had received local
      therapy repeatedly for 20 years. In 2012, he underwent hepatic right lobectomy
      for recurrence of HCC. Multiple recurrences were found in the hepatic remnant,
      and transcatheter arterial chemoembolization (TACE) was performed. Considering
      his condition, a small dose of sorafenib (200 mg per day) was administered. He
      complained of general fatigue, so we prolonged the administration interval (200
      mg every other day). Thereafter, compliance improved and long-term stable disease
      (long SD), for more than 6 months, long SD was achieved. Case 2: A7 5-year-old
      man with HCC was treated by TACE repeatedly for multiple recurrences after liver
      resection (segment 6). In 2008, metastases to the thoracic vertebra and left rib
      were treated by radiation therapy and radiofrequency ablation, respectively.
      Subsequently, sorafenib (400 mg per day) was administered. We reduced the dose of
      sorafenib to less than 400 mg per day because of diarrhea, hypertension, and
      general fatigue. Thereafter, long SD was achieved despite the small dose of
      sorafenib. We report here 2 cases of HCC where we achieved long SD in spite of
      treating with a small dose of sorafenib.

PMID- 26197752
TI  - [A Case of Fanconi Syndrome Induced by Zoledronic Acid in a Metastatic Colorectal
      Cancer Patient].
AB  - A 60s-year-old woman with metastatic colorectal cancer was treated using mFOLFOX6
      plus bevacizumab. Zoledronic acid was also administered owing to the presence of
      bone metastasis. The patient was admitted to our hospital with progressive
      hypokalemia, hypocalcemia, hypophosphatemia, and proximal renal tubular
      dysfunction. A diagnosis of Fanconi syndrome was made, and was believed to be
      induced by zoledronic acid treatment. This treatment was discontinued, and the
      patient's renal tubular function recovered. Denosumab was subsequently
      administered to treat the bone metastasis, and no renal tubular dysfunction
      occurred. It was possible to continue chemotherapy, and a complete response was
      obtained. Fanconi syndrome induced by zoledronic acid is rare, but it may hinder
      chemotherapy. Therefore, monitoring renal tubular function is recommended during
      therapy with zoledronic acid.

PMID- 26197753
TI  - [Successful Administration of Regorafenib to a Metastatic Colon Cancer Patient
      with Impaired Performance Status by Reducing the Initial Dose].
AB  - A 59-year-old woman had recurrences in the spleen and lung 10 years after radical
      excision of cecal cancer. After 27 months of treatment with 5
      fluorouracil/Leucovorin, oxaliplatin, irinotecan, bevacizumab, and anti-EGFR
      antibodies, multiple bone metastases and a left adrenal metastasis developed, and
      the patient's performance status (PS) deteriorated to grade 3. Regorafenib was
      administered at 80 mg/day. The pain and appetite improved within 2 courses, and
      her PS improved from grade 3 to 2. Regorafenib was increased to 120 mg/day for
      the 2nd course, and the patient was treated for 5 months without severe adverse
      effects. Regorafenib is considered to be a salvage-line treatment only for
      patients in relatively good condition, because full-dose regorafenib treatment
      often leads to severe adverse effects. Dose escalation of regorafenib from the
      low initial dose of 80 mg/day may be a safe and effective way of providing an
      opportunity of this chemotherapy to patients with impaired PS.

PMID- 26197754
TI  - [A Case of Rectal Cancer with Portal Vein Tumor Thrombosis Successfully Treated
      with First-Line Panitumumab Monotherapy].
AB  - The patient was a 66-year-old man with progressive rectal cancer and portal vein
      tumor thrombosis near the porta hepatis. A subileus further complicated the
      situation. Therefore, an abdominoperineal resection was performed. As the KRAS
      gene was the wild-type gene, we administered panitumumab monotherapy every 2
      weeks after the operation. Two months after the operation, the tumor marker
      levels were normal and the tumor size was reduced. Hence, oral capecitabine, with
      1-week administration followed by 1-week of rest, was added to the therapy. In
      the 12 months after the operation, panitumumab was stopped once, and treatment
      with capecitabine alone was continued in the same schedule. As of 26 months, the
      disease showed a partial response using capecitabine alone. We report our
      experience of a case of rectal cancer with portal vein tumor thrombosis that was
      successfully treated with panitumumab. 

PMID- 26197755
TI  - [A Case of Pneumocystis Pneumonia during Chemotherapy for Recurrent Ovarian
      Cancer].
AB  - A 53-year-old patient with recurrent ovarian clear cell adenocarcinoma developed
      fever (39 degrees C) and cough on day 28 of liposomal doxorubicin chemotherapy,
      the 4th cycle of the 4th regimen since initial treatment. Drug-induced
      interstitial pneumonia was suspected from a chest CT image showing diffuse ground
      glass opacities; however, we deduced pneumocystis pneumonia from the elevated
      serum beta-D-glucan levels. After effective treatment with sulfamethoxazole and
      amphotericin B, the patient's symptoms and radiological findings improved.
      Pneumocystis pneumonia is an opportunistic infection that poses a risk not only
      for patients undergoing aggressive immunosuppressive therapy, those infected with
      HIV, and those with transplants, but also for patients undergoing chemotherapy.
      When pneumonia is diagnosed during chemotherapy, it is essential to consider the
      possibility of pneumocystis pneumonia.

PMID- 26197756
TI  - [A Patient with Recurrent Ovarian Cancer Who Was Hypersensitive to Carboplatin
      Exhibited Complete Response to Gemcitabine and Nedaplatin].
AB  - A 57-year-old multiparous woman with FIGO stage IV ovarian cancer underwent
      primary surgery and was administered postoperative chemotherapy consisting of
      paclitaxel and carboplatin (TC). Complete response was confirmed on computed
      tomography. After a 20-month platinum free interval (PFI), an elevated serum
      CA125 level and recurrence in the peritoneum were confirmed, and she was
      retreated with TC as second-line chemotherapy. A hypersensitivity reaction
      occurred after administering the second dose of carboplatin; therefore,
      carboplatin was changed to nedaplatin. Complete response was confirmed on
      computed tomography, and the serum CA125 level returned to normal. After an 8
      month PFI, an elevated serum CA125 level and recurrence in the peritoneum and
      liver were confirmed, and she was treated with 6 cycles of combination
      chemotherapy consisting of gemcitabine (1,000 mg/m2: day 1 and 8 q3 weeks)and
      nedaplatin (80 mg/m2: day 1 q3 weeks). Only cytopenia (grade 2: CTCAE v4.0) was
      noted as a complication during chemotherapy. Complete response was confirmed on
      computed tomography. This report presents the case of a patient with recurrent
      ovarian cancer who was platinum sensitive and successfully treated with
      gemcitabine and nedaplatin after showing a hypersensitivity reaction to
      carboplatin.

PMID- 26197757
TI  - [Search for Factors Related to Vascular Pain Expression upon Administration of
      Oxaliplatin into a Peripheral Vein].
AB  - We investigated the relationship between vascular pain and various
      characteristics (age, sex, cancer stage, performance status [PS], height, weight,
      body mass index [BMI], body surface area, oxaliplatin dose, and presence and
      absence of the initial administration of dexamethasone) in colorectal cancer
      patients who were administered initial doses of oxaliplatin intravenously. The
      study population included 29 patients treated at Higashi Totsuka Memorial
      Hospital between June 2010 and April 2014. One-way analysis of variance showed
      that vascular pain was significantly associated with weight (p=0.015), body
      surface area (p=0.013), and oxaliplatin doses (p=0.0026), where the significance
      level was p=0.05. Logistic regression analysis and the likelihood ratio test
      demonstrated that the likelihood of vascular pain increased with the increase in
      the oxaliplatin dose. According to the cut-off value of vascular pain determined
      using the receiver operating characteristic (ROC) analysis, a single dose of
      oxaliplatin was determined to be 175 mg or more. According to the cut-off value
      established using the ROC analysis, a single dose of oxaliplatin at which
      vascular pain is expressed was determined to be 175 mg or more. At this dose, 13
      patients complained of vascular pain and 8 did not. At doses less than 175 mg,
      none of the 8 patients complained of vascular pain. These results suggest that
      lowering the diluted concentration and reducing the infusion rate of
      intravenously administered oxaliplatin may reduce vascular pain.

PMID- 26197758
TI  - A retrospective, longitudinal study estimating the association between
      interdialytic weight gain and cardiovascular events and death in hemodialysis
      patients.
AB  - BACKGROUND: Greater interdialytic weight gain (IDWG) is associated with risk of
      all-cause mortality and hospitalization. Dialysis patients are also at greater
      risk of cardiovascular (CV) events than patients without kidney disease. This
      retrospective study examined the potential association between IDWG and specific
      types of CV events. METHODS: Data were obtained from United States Renal Data
      System claims and the electronic health records of Medicare patients who
      initiated hemodialysis between 01 January 2007 and 31 December 2008 at a large
      dialysis organization. Absolute IDWG was defined as predialysis weight minus
      postdialysis weight from the prior treatment, and relative IDWG was calculated as
      percentage of postdialysis weight with mean values for each, calculated over
      dialysis days 91 to 180. Patient outcomes were considered beginning on day 181,
      continuing until death, discontinuation of care, censoring, or study end (31
      December 2009). Outcomes included all-cause mortality, CV mortality,
      hospitalization for nonfatal heart failure/volume overload, hospitalization for
      nonfatal myocardial infarction, MACE (a composite measure of nonfatal myocardial
      infarction, nonfatal ischemic stroke, or CV death), and MACE+ (events comprising
      MACE as well as arrhythmia, nonfatal hemorrhagic stroke, or hospitalization for
      heart failure). Associations between IDWG and outcomes over the exposure period
      were estimated using proportional hazards regression and adjusted for baseline
      characteristics. RESULTS: 39,256 patients qualified for analysis. In general,
      associations of relative IDWG with outcomes were more potent, consistent, and
      monotonic than those for absolute IDWG. Relative IDWG > 3.5 % body weight was
      independently associated with all outcomes studied: point estimates ranged from
      1.18 (myocardial infarction) to 1.26 (CV mortality) and were consistent among
      patients with and without diabetes, and with and without baseline heart failure.
      Absolute IDWG > 3 kg was associated with outcomes other than myocardial
      infarction: point estimates ranged from 1.11 (MACE) to 1.20 (heart failure).
      CONCLUSIONS: Greater IDWG is associated with an increased risk of CV morbid
      events. Strategies that mitigate IDWG may improve CV health and survival among
      hemodialysis patients.

PMID- 26197760
TI  - beta-Mannosylation with 4,6-benzylidene protected mannosyl donors without
      preactivation.
AB  - Mannosylations with benzylidene protected mannosyl donors were found to be beta
      selective even when no preactivation was performed. It was also found that the
      kinetic beta-product in some cases anomerizes fast to the thermodynamically
      favored alpha-anomer under typical reaction conditions. 

PMID- 26197759
TI  - Pharmaceuticals and Surfactants from Alga-Derived Feedstock: Amidation of Fatty
      Acids and Their Derivatives with Amino Alcohols.
AB  - Amidation of renewable feedstocks, such as fatty acids, esters, and Chlorella
      alga based biodiesel, was demonstrated with zeolites and mesoporous materials as
      catalysts and ethanolamine, alaninol, and leucinol. The last two can be derived
      from amino acids present in alga. The main products were fatty alkanol amides and
      the corresponding ester amines, as confirmed by NMR and IR spectroscopy. Thermal
      amidation of technical-grade oleic acid and stearic acid at 180  degrees C with
      ethanolamine were non-negligible; both gave 61% conversion. In the amidation of
      stearic acid with ethanolamine, the conversion over H-Beta-150 was 80% after 3 h,
      whereas only 63% conversion was achieved for oleic acid; this shows that a
      microporous catalyst is not suitable for this acid and exhibits a wrinkled
      conformation. The highest selectivity to stearoyl ethanolamide of 92% was
      achieved with mildly acidic H-MCM-41 at 70% conversion in 3 h at 180  degrees C.
      Highly acidic catalysts favored the formation of the ester amine, whereas the
      amide was obtained with a catalyst that exhibited an optimum acidity. The
      conversion levels achieved with different fatty acids in the range C12-C18 were
      similar; this shows that the fatty acid length does not affect the amidation
      rate. The amidation of methyl palmitate and biodiesel gave low conversions over
      an acidic catalyst, which suggested that the reaction mechanism in the amidation
      of esters was different.

PMID- 26197761
TI  - Glass and Plastics Platforms for Foldable Electronics and Displays.
AB  - Reversibly, repeatedly foldable electronics and displays are enabled by employing
      engineered glass or plastics substrates, where folding deformation is localized
      in thinned parts only. This design concept can further be extended to dual
      folding, leading to size reduction down to 1/4. Notably, the foldable electronics
      and displays can be implemented with no need to introduce any novel materials. 

PMID- 26197762
TI  - Improvement in quality of life after robotic surgery results in patient
      satisfaction.
AB  - BACKGROUND: There are well-described benefits to minimally invasive surgery
      including decreased blood loss, shorter hospital-stay, and faster recovery. The
      role of robotic surgery in gynecologic oncology has become increasingly
      prominent; however limited data are available on quality of life (QOL) after
      robotic surgery. METHODS: In this prospective, IRB-approved study, women
      scheduled for robotic surgery for a gynecologic indication between May 2008 and
      February 2012 completed validated QOL measures at baseline, 6 weeks (6wk), and 4
      months postoperative (4mo). Functional status (SF-12), symptom severity and
      interference (MDASI), sexual function (FSFI), and satisfaction with decision
      (SWD) were assessed at relevant time points. Differences between groups were
      evaluated using the Mann-Whitney test. RESULTS: Among 408 women who underwent
      robotic surgery 278 (68%) completed the QOL measures. Median age was 55.6 years
      (range 25.7-85.1). Median BMI was 31.3kg/m(2). The majority of patients were
      white (75%). The most common indication for surgery was endometrial
      cancer/hyperplasia (59.7%). While physical functioning declined from baseline to
      6wk (51.4 to 41.6, p<0.001), it improved by 4mo (53.5). Mental functioning
      improved over time (baseline 48.6, 6wk 52.8, and 4mo 55.6, p<0.001). Symptom
      severity decreased over time (p<0.001) as did symptom interference (p<0.001).
      Sexual function improved significantly from baseline (8.6) to 4mo (20.2,
      p<0.001). Patients were satisfied with their decision making (SWD=30).
      CONCLUSION: In this prospective study, general health, symptom burden and sexual
      function returned to or improved beyond baseline levels within 6 weeks of
      surgery. Overall, women were satisfied with their decision to undergo robotic
      surgery.

PMID- 26197763
TI  - Cerebral functional connectivity periodically (de)synchronizes with anatomical
      constraints.
AB  - This paper studies the link between resting-state functional connectivity (FC),
      measured by the correlations of fMRI BOLD time courses, and structural
      connectivity (SC), estimated through fiber tractography. Instead of a static
      analysis based on the correlation between SC and FC averaged over the entire fMRI
      time series, we propose a dynamic analysis, based on the time evolution of the
      correlation between SC and a suitably windowed FC. Assessing the statistical
      significance of the time series against random phase permutations, our data show
      a pronounced peak of significance for time window widths around 20-30 TR (40-60
      s). Using the appropriate window width, we show that FC patterns oscillate
      between phases of high modularity, primarily shaped by anatomy, and phases of low
      modularity, primarily shaped by inter-network connectivity. Building upon recent
      results in dynamic FC, this emphasizes the potential role of SC as a transitory
      architecture between different highly connected resting-state FC patterns.
      Finally, we show that the regions contributing the most to these whole-brain
      level fluctuations of FC on the supporting anatomical architecture belong to the
      default mode and the executive control networks suggesting that they could be
      capturing consciousness-related processes such as mind wandering.

PMID- 26197765
TI  - Long-term outcome of endovascular intervention in hepatic venous outflow
      obstruction following pediatric liver transplantation.
AB  - The purpose of our study was to address the long-term outcome of angioplasty and
      stent placement for hepatic venous outflow obstruction following pediatric liver
      transplantation. From October 1999 to December 2011, 20 stenotic lesions were
      confirmed to constitute hepatic venous outflow obstruction in 18 pediatric
      patients (13 boys, 5 girls) among 152 pediatric patients following liver
      transplantation and were managed with endovascular intervention. Stent placement
      was favored over additional angioplasty in patients of preadolescent or
      adolescent age (>8 years old), after 1 or 2 sessions of balloon angioplasty. The
      primary patency and assisted primary patency were estimated using the Kaplan
      Meier method. A total of 32 procedures (24 balloon angioplasties, 8 stent
      placements) were conducted. The technical success rate was 90.6% (29/32).
      Clinical success was achieved in 15 of 18 patients (clinical success rate of
      83.3%). Major complications did not occur in our study. Median follow-up was 91.5
      months (interquartile range, 54.7-137.3 months) for the 18 patients. The 1-year,
      3-year, 5-year, and 10-year primary patencies of the 20 treated lesions were
      63.5%, 57.8%, 57.8%, and 57.8%, respectively. The 1-year, 3-year, 5-year, and 10
      year assisted-primary patencies of the lesions were 100%, 100%, 100%, and 100%,
      respectively. Of the 6 patients of preadolescent or adolescent age, 5 patients
      underwent stent placement procedures, and the stents were patent during the
      follow-up period of 57.3-162.5 months (median, 72.7 months). In conclusion,
      endovascular intervention is very effective in hepatic venous outflow obstruction
      following pediatric liver transplantation. In addition, early stent placement in
      patients of preadolescent or adolescent age can provide a safe and favorable long
      term outcome.

PMID- 26197764
TI  - Self- and proxy reports of quality of life among adolescents living in
      residential youth care compared to adolescents in the general population and
      mental health services.
AB  - BACKGROUND: Child welfare services are aimed at providing care and protection,
      fostering well-being and prosocial behaviour. Thus, Quality of Life (QoL) should
      be an important outcome measure in Residential Youth Care (RYC) institutions.
      However, the dearth of research in this area gives rise to serious concern. The
      present study is the first large scale, nationwide study assessing QoL among
      adolescents living in RYC. To provide a reference frame, adolescent self- and
      primary contact proxy reports were compared to the general population and to
      adolescent outpatients in Child and Adolescent Mental Health Service (CAMHS).
      Also, we investigated the association between self-report of QoL in adolescents
      living in RYC and proxy reports of their primary contacts at the institution.
      METHODS: All residents between the ages of 12-23 years living in RYC in Norway
      were the inclusion criteria. Eighty-six RYC institutions (with 601 eligible
      youths) were included, 201 youths/ parents did not give their consent. Finally,
      400 youths aged 12-20 years participated, yielding a response rate of 67%. As a
      reference frame for comparison, a general population (N = 1444) and an outpatient
      sample of adolescents in CAMHS (N = 68) were available. We used the Questionnaire
      for Measuring Health-related Quality of Life in Children and Adolescents (KINDL
      R). General Linear Model analyses (ANCOVA) were conducted with five KINDL life
      domains as dependent variables and group as independent variable. RESULTS: Self-
      and proxy reports of QoL in adolescents living in RYC revealed a significantly (p
      < 0.001) poorer QoL compared to the general population on the life domains
      Physical- and Emotional well-being, Self-esteem, and relationship with Friends.
      Adolescents evaluated their physical well-being as worse compared to adolescents
      in CAHMS. Self- and proxy reports in RYC differed significantly on two of five
      life domains, but correlated low to moderate with each other. CONCLUSIONS: The
      results in this study raise major concerns about the poor QoL of the adolescents
      living in RYC, thereby challenging the child welfare system and decision makers
      to take action to improve the QoL of this group. The use of QoL as outcome
      measures is highly recommended.

PMID- 26197766
TI  - Postnatal gestational diabetes mellitus follow-up: Australian women's
      experiences.
AB  - PROBLEM: Postnatal follow-up screening is recommended for all women diagnosed
      with gestational diabetes mellitus (GDM). However follow-up rates are poor and
      highly variable in Australia and internationally. The reasons that mothers are
      not completing recommended postnatal screening after GDM diagnosis are not well
      understood or studied. The quality of communication may be an important influence
      on the completion of postnatal GDM follow-up. AIM: To explore and assess women's
      communication experiences of postnatal GDM follow-up. METHODS: Theoretical,
      purposeful sampling was used to identify women diagnosed with GDM. Convergent
      interviews explored participants' communication experiences with GDM and
      postnatal follow-up. Transcripts were provided to and updated by participants.
      Data was analysed with Leximancer((r)) (V4, 2011) automated content analysis
      software. SETTING AND PARTICIPANTS: This research was conducted at a major
      tertiary referral hospital in Queensland, Australia, between December 2012 and
      July 2013. Women participating in maternity shared care and diagnosed with GDM
      were interviewed (n=13). FINDINGS: Five themes, all concerned with obtaining
      information, were identified: diagnosis of GDM; seeking GDM information;
      accessing specialist services; need for postnatal GDM follow-up; and completing
      GDM follow-up. Results were interpreted using Communication Accommodation Theory
      (CAT) to explore whether and how the information needs of women were
      accommodated. Women's interpretations of communication events influenced their
      knowledge, perceptions and motivation to complete recommended postnatal follow
      up. CONCLUSION: Accommodation of the communication and information needs of women
      with GDM may be an effective strategy for clinicians to encourage completion of
      recommended postnatal GDM follow-up.

PMID- 26197767
TI  - Outcome of Laparoscopic Versus Open Resection for Transverse Colon Cancer.
AB  - BACKGROUND: Laparoscopic resection for transverse colon cancer remains
      controversial. The aim of this study is to investigate the short- and long-term
      outcomes of laparoscopic surgery for transverse colon cancer. METHODS: A total of
      278 patients with transverse colon cancer from a single institution were
      included. All patients underwent curative surgery, 156 patients underwent
      laparoscopic resection (LR), and 122 patients underwent open resection (OR). The
      short- and long-term results were compared between two groups. RESULTS: Baseline
      demographic and clinical characteristics were comparable between two groups.
      Conversions were required in eight (5.1 %) patients. LR group was associated with
      significantly longer median operating time (180 vs. 140 min; P < 0.001). Median
      estimated blood loss was significantly less in LR group (90 vs. 100 ml; P =
      0.001). Time to first flatus and oral intake was significantly earlier in LR
      group. Perioperative mortality and morbidity rate were not significantly
      different between two groups. Tumor size, number of lymph nodes harvested, length
      of proximal, and distal resection margin were comparable between two groups.
      Postoperative hospital stay was significantly shorter in LR group (9 vs. 10d; P <
      0.001). Five-year disease-free survival and overall survival rate were similar
      between two groups. CONCLUSIONS: Laparoscopic resection for transverse colon
      cancer is associated with better short-term outcomes and equivalent long-term
      oncologic outcomes.

PMID- 26197768
TI  - Adjuvant sequential chemo and radiotherapy improves the oncological outcome in
      high risk endometrial cancer.
AB  - OBJECTIVE: Evaluation of the impact of sequential chemoradiotherapy in high risk
      endometrial cancer (EC). METHODS: Two hundred fifty-four women with stage IB
      grade 3, II and III EC (2009 FIGO staging), were included in this retrospective
      study. RESULTS: Stage I, II, and III was 24%, 28.7%, and 47.3%, respectively.
      Grade 3 tumor was 53.2% and 71.3% had deep myometrial invasion. One hundred sixty
      five women (65%) underwent pelvic (+/- aortic) lymphadenectomy and 58 (22.8%) had
      nodal metastases. Ninety-eight women (38.6%) underwent radiotherapy, 59 (23.2%)
      chemotherapy, 42 (16.5%) sequential chemoradiotherapy, and 55 (21.7%) were only
      observed. After a median follow-up of 101 months, 78 women (30.7%) relapsed and
      91 women (35.8%) died. Sequential chemoradiotherapy improved survival rates in
      women who did not undergo nodal evaluation (disease-free survival [DFS], p=0.040;
      overall survival [OS], p=0.024) or pelvic (+/- aortic) lymphadenectomy (DFS,
      p=0.008; OS, p=0.021). Sequential chemoradiotherapy improved both DFS (p=0.015)
      and OS (p=0.014) in stage III, while only a trend was found for DFS (p=0.210) and
      OS (p=0.102) in stage I-II EC. In the multivariate analysis, only age (<= 65
      years) and sequential chemoradiotherapy were statistically related to the
      prognosis. CONCLUSION: Sequential chemoradiotherapy improves survival rates in
      high risk EC compared with chemotherapy or radiotherapy alone, in particular in
      stage III.

PMID- 26197769
TI  - Pretreatment risk factors for parametrial involvement in FIGO stage IB1 cervical
      cancer.
AB  - OBJECTIVE: All patients with stage IB1 cervical cancer do not need to undergo
      parametrectomy. Some low-risk criteria for parametrial involvement (PI) have been
      proposed based on pathological findings. The aim of this study was to determine
      pretreatment risk factors for PI in stage IB1 cervical cancer. METHODS: We
      retrospectively reviewed 115 patients with stage IB1 cervical cancer who
      underwent radical hysterectomy or radical trachelectomy. Magnetic resonance
      imaging (MRI) was performed and serum concentrations of squamous cell carcinoma
      antigen (SCC-Ag) and cancer antigen 125 (CA-125) were determined in all patients
      before initial treatment. The following pretreatment factors were investigated:
      histological variant, maximum tumor diameter, tumor volume (volume index), pelvic
      lymph node enlargement, and serum tumor markers. Logistic regression analysis was
      used to select the independent risk factors for PI. RESULTS: Eighteen of the 115
      patients (15.7%) were pathologically diagnosed with PI. Multivariate analysis
      confirmed the following independent risk factors for PI: MRI-based tumor diameter
      >= 25 mm (odds ratio [OR], 9.9; 95% confidence interval [CI], 2.1 to 48.1), MRI
      based volume index >= 5,000 mm3 (OR, 13.3; 95% CI, 1.4 to 125.0), and positive
      serum tumor markers SCC-Ag >= 1.5 ng/mL or CA-125 >= 35 U/mL (OR, 5.7; 95% CI,
      1.3 to 25.1). Of 53 patients with no risk factors for PI, none had PI.
      CONCLUSION: Less radical surgery may become one of the treatment options for
      stage IB1 cervical cancer patients with MRI-based tumor diameter <25 mm, MRI
      based volume index <5,000 mm3, and negativity for SCC-Ag and CA-125.

PMID- 26197770
TI  - Synchronous and metachronous malignancy in endometrial cancer patients treated in
      a tertiary care center of Thailand.
AB  - OBJECTIVE: To evaluate the prevalence and features of non-endometrial cancers in
      Thai endometrial cancer (EC) patients. METHODS: EC patients treated in our
      institution were identified and the following data were collected: age, EC stage,
      histopathology, adjuvant therapy, other cancers, living status, and cause of
      death. RESULTS: The mean age of the 344 patients was 56.8 +/- 10.8 years. Fifty
      (14.5%) had other synchronous and metachronous cancers. Mean ages of the patients
      with or without other cancers were not significantly different, 55.7 +/- 10.04
      years versus 57.1 +/- 11.0 years, respectively (p=0.358). History of any cancer
      in the family and tumor in the lower uterine segment were more frequent among the
      patients with other cancers (6.0% vs. 1.7%, p=0.095; 12.0% vs. 1.0%, p<0.001;
      respectively). Six patients had >= 2 other cancers. Ovarian, breast, and colon
      were the three most common other cancers. After a median follow-up of 57.1
      months, 18.3% of patients had died: 30.0% of patients with other cancers and
      16.3% of those without other cancers. The corresponding EC deaths were 14.0% and
      11.2%. The 5-year overall survival was significantly lower in patients who had
      other cancers: 79.3% (95% confidence interval [CI], 68.3 to 90.3) vs. 86.0% (95%
      CI, 81.7 to 90.3) than in those without (p=0.023). However, the corresponding
      disease-specific survival was not significantly different: 85.1% (95% CI, 75.5 to
      94.7) compared with 89.0% (95% CI, 85.1 to 92.9), respectively (p=0.514).
      CONCLUSION: Thai EC patients had a high incidence of other cancers. Overall
      survival of EC patients who had other cancers was worse than those without, while
      disease-specific survival was not significantly different.

PMID- 26197771
TI  - Clinical significance of systematic retroperitoneal lymphadenectomy during
      interval debulking surgery in advanced ovarian cancer patients.
AB  - OBJECTIVE: To investigate the clinical significance of systematic retroperitoneal
      lymphadenectomy during interval debulking surgery (IDS) in advanced epithelial
      ovarian cancer (EOC) patients. METHODS: We retrospectively reviewed the medical
      records of 124 advanced EOC patients and analyzed the details of neoadjuvant
      chemotherapy (NACT), IDS, postoperative treatment, and prognoses. RESULTS:
      Following IDS, 98 patients had no gross residual disease (NGRD), 15 had residual
      disease sized <1 cm (optimal), and 11 had residual disease sized >=1 cm
      (suboptimal). Two-year overall survival (OS) and progression-free survival (PFS)
      rates were 88.8% and 39.8% in the NGRD group, 40.0% and 13.3% in the optimal
      group (p<0.001 vs. NGRD for both), and 36.3% and 0% in the suboptimal group,
      respectively. Five-year OS and 2-year PFS rates were 62% and 56.1% in the lymph
      node-negative (LN-) group and 26.2% and 24.5% in the lymph node-positive (LN+)
      group (p=0.0033 and p=0.0024 vs. LN-, respectively). Furthermore, survival in the
      LN+ group, despite surgical removal of positive nodes, was the same as that in
      the unknown LN status group, in which lymphadenectomy was not performed (p=0.616
      and p=0.895, respectively). Multivariate analysis identified gross residual tumor
      during IDS (hazard ratio, 3.68; 95% confidence interval, 1.31 to 10.33 vs. NGRD)
      as the only independent predictor of poor OS. CONCLUSION: NGRD after IDS improved
      prognosis in advanced EOC patients treated with NACT-IDS. However, while
      systematic retroperitoneal lymphadenectomy during IDS may predict outcome, it
      does not confer therapeutic benefits.

PMID- 26197772
TI  - Identification of high-affinity VEGFR3-binding peptides through a phage-displayed
      random peptide library.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) interaction with its
      receptor, VEGFR-3/Flt-4, regulates lymphangiogenesis. VEGFR-3/Flt-4 expression in
      cancer cells has been correlated with clinical stage, lymph node metastasis, and
      lymphatic invasion. The objective of this study is to identify a VEGFR-3/Flt-4
      interacting peptide that could be used to inhibit VEGFR-3 for ovarian cancer
      therapy. METHODS: The extracellular fragment of recombinant human VEGFR-3/Flt-4
      (rhVEGFR-3/Flt-4) fused with coat protein pIII was screened against a phage
      displayed random peptide library. Using affinity enrichment and enzyme-linked
      immunosorbent assay (ELISA) screening, positive clones of phages were amplified.
      Three phage clones were selected after four rounds of biopanning, and the
      specific binding of the peptides to rhVEGFR-3 was detected by ELISA and compared
      with that of VEGF-D. Immunohistochemistry and immunofluorescence analyses of
      ovarian cancer tissue sections was undertaken to demonstrate the specificity of
      the peptides. RESULTS: After four rounds of biopanning, ELISA confirmed the
      specificity of the enriched bound phage clones for rhVEGFR-3. Sequencing and
      translation identified three different peptides. Non-competitive ELISA revealed
      that peptides I, II, and III had binding affinities for VEGFR-3 with K(aff)
      (affinity constant) of 16.4+/-8.6 MUg/mL (n=3), 9.2+/-2.1 MUg/mL (n=3), and
      174.8+/-31.1 MUg/mL (n=3), respectively. In ovarian carcinoma tissue sections,
      peptide III (WHWLPNLRHYAS), which had the greatest binding affinity, also co
      localized with VEGFR-3 in endothelial cells lining lymphatic vessels; its
      labeling of ovarian tumors in vivo was also confirmed. CONCLUSION: These finding
      showed that peptide III has high specificity and activity and, therefore, may
      represent a potential therapeutic approach to target VEGF-VEGFR-3 signaling for
      the treatment or diagnosis of ovarian cancer.

PMID- 26197773
TI  - Role of aggressive surgical cytoreduction in advanced ovarian cancer.
AB  - Ovarian cancer is the eighth most frequent cancer in women and is the most lethal
      gynecologic malignancy worldwide. The majority of ovarian cancer patients are
      newly diagnosed presenting with advanced-stage disease. Primary cytoreductive
      surgery and adjuvant taxane- and platinum-based combination chemotherapy are the
      standard treatment for advanced ovarian cancer. A number of studies have
      consistently shown that successful cytoreductive surgery and the resultant
      minimal residual disease are significantly associated with survival in patients
      with this disease. Much has been written and even more debated regarding the
      competing perspectives of biology of ovarian cancer versus the value of
      aggressive surgical resection. This review will focus on the current evidences
      and outcomes supporting the positive impact of aggressive surgical effort on
      survival in the primary management of ovarian cancer. 

PMID- 26197774
TI  - Pulmonary metastasectomy in uterine malignancy: outcomes and prognostic factors.
AB  - OBJECTIVE: The aim of this study was to investigate outcomes in uterine cancer
      patients undergoing pulmonary metastasectomy and prognostic factors associated
      with survival after the procedure. METHODS: A retrospective study was performed
      in 29 uterine cancer patients who underwent surgical resection of pulmonary
      metastatic lesions at Samsung Medical Center between June 1995 and December 2011.
      RESULTS: Histopathology showed carcinoma in 17 patients (58.6%) and sarcoma in 12
      patients (41.4%). Of the 29 patients, 17 (58.6%) had less than three pulmonary
      metastatic lesions. Eight (27.6%) had symptoms related to lung metastasis. The 5
      year survival rate after pulmonary metastasectomy for the entire cohort was
      48.2%. On univariate and multivariate analysis, the presence of pulmonary
      symptoms and more than three lesions of metastasis were associated with poor
      survival after pulmonary metastasectomy. CONCLUSION: Pulmonary metastasectomy for
      uterine cancer is an acceptable treatment in selected patients. Patients with
      more than three pulmonary metastatic lesions and pulmonary symptoms related to
      lung metastasis could expect to have worse prognosis after pulmonary
      metastasectomy.

PMID- 26197775
TI  - Fertility-sparing surgery in high-risk ovarian cancer.

PMID- 26197776
TI  - Palonosetron versus granisetron in combination with aprepitant for the prevention
      of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer.
AB  - OBJECTIVE: There is no research regarding the appropriate antiemetic agents for
      female patients, especially those receiving moderately emetogenic chemotherapy
      (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor
      with/without aprepitant in patients with gynecological cancer treated with the TC
      (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients
      diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The
      patients were randomly assigned to receive a 5-HT3 receptor antagonist, either
      palonosetron in the first cycle followed by granisetron in the second cycle or
      vice versa. In the third cycle, all patients received a combination of the 5-HT3
      receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs
      were administered, palonosetron consistently produced an equivalent complete
      response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87)
      and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary
      intake, palonosetron exhibited similar efficacy to granisetron in the acute phase
      (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However,
      in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor
      antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor
      antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients
      to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001).
      CONCLUSION: The addition of aprepitant therapy was more effective than the
      control therapy of a 5-HT3 receptor antagonist, and dexamethasone in
      gynecological cancer patients treated with the TC regimen.

PMID- 26197778
TI  - Ring-tension adjusted ethylene polymerization by aryliminocycloheptapyridyl
      nickel complexes.
AB  - The stoichiometric reactions of 5,6,7,8-tetrahydrocycloheptapyridin-9-one
      (cycloheptapyridin-9-one) with various anilines lead to corresponding mixtures of
      9-aryliminocycloheptapyridine and the isomeric 9-arylamino-5,6,7
      trihydrocycloheptapyridine derivatives; these compounds further reacted with
      nickel dichloride to form 9-aryliminocycloheptapyridyl nickel chlorides,
      respectively. The new organic compounds were analyzed by the NMR measurements,
      and all the organic and complex compounds were characterized by the FT-IR
      spectroscopy and elemental analysis. In addition, the molecular structures of
      representative nickel complexes and , determined by means of single-crystal X-ray
      diffraction, were found to be binuclear dimers with distorted square-pyramidal
      geometry around the nickel centers. On activation with either ethylaluminium
      sesquichloride (Et3Al2Cl3) or methylaluminoxane (MAO), all nickel complex pre
      catalysts exhibited high activities of up to 7.80 * 10(6) g PE mol(-1) (Ni) h(-1)
      toward ethylene polymerization and produced highly branched polyethylenes in
      narrow polydispersity. The title nickel complexes showed comparable activities
      with 8-arylimino-5,6,7-trihydroquinolyl nickel analogues; whilst both exhibited
      higher activities than did the 2-iminopyridyl nickel analogues due to the
      enhancement of the ring-tension of cyclic-fused pyridine derivatives. 

PMID- 26197777
TI  - Prevalence of Fabry disease in dialysis patients: Japan Fabry disease screening
      study (J-FAST).
AB  - BACKGROUND: In Fabry disease, progressive glycolipid accumulation leads to damage
      in kidney and other organs. This study was designed to determine the prevalence
      rate of Fabry disease in Japanese dialysis patients. METHODS: All dialysis
      patients agreeing to Japan Fabry disease screening study (J-FAST) with informed
      consent were selected except for Fabry disease. The screening was performed by a
      method of measuring plasma and/or leukocytes lysosomal alpha-galactosidase A
      protein level and alpha-galactosidase A activity. If positive, genetic analysis
      was carried out upon patient's agreement. RESULTS: J-FAST dealt with 8547
      patients (male 5408, female 3139). At the tertiary examination, 26 out of 8547
      patients were found to be positive. Six out of 26 patients could not accept
      genetic analysis because of death. Remaining 20 patients agreed with genetic
      analysis; then 2 patients (male 2, female 0) had a variation of the alpha-Gal
      gene and 11 patients showed E66Q variations. Therefore, the frequency of Fabry
      disease in J-FAST was 0.04 % (2/5408) in males and 0 % (0/3139) in females, and
      then 0.02 % (2/8547) in all patients. The presumptive clinical diagnoses of end
      stage kidney disease (ESKD) were 10 chronic glomerulonephritis, 7 diabetic
      nephropathy, 3 unknown etiology, 3 nephrosclerosis, 1 gouty nephropathy, 1
      autosomal dominant polycystic kidney disease and 1 renal tuberculosis among 26
      tertiary positive patients. Two male Fabry patients were initially diagnosed as
      nephrosclerosis and chronic glomerulonephritis. CONCLUSIONS: The prevalence rate
      of Fabry disease in J-FAST was 0.02 %. Moreover, Fabry disease could not be ruled
      out as the clinical diagnosis of ESKD.

PMID- 26197780
TI  - Posttraumatic stress disorder symptoms in close relatives of intensive care unit
      patients: Prevalence data resemble that of earthquake survivors in Chile.
AB  - INTRODUCTION: Posttraumatic stress disorder (PTSD) in relatives of intensive care
      unit (ICU) patients has not been fully described. We studied potential
      relationships between PTSD and specific patients' conditions and relatives'
      psychologic characteristics. METHODS: This is a prospective study of family
      caregivers of ICU patients. Patients' clinical and physiologic variables were
      recorded. At admission (time I), family caregivers' sociodemographic and
      psychologic variables were assessed, using specific questionnaires. Reassessment
      occurred at 2 to 4 days (time II) and 60 days (time III). RESULTS: Of 105
      enrolled caregivers, 83 completed follow-up. They were mainly female adults and
      first-degree relatives. Caregiver's baseline anxiety and depression symptoms were
      observed in 30.4% and 17.4%, respectively. Higher levels associated positively
      with PTSD symptoms (PS). At time III, 22.89% of caregivers met criteria for PTSD,
      similar to Chilean general population after the 2010's massive earthquake.
      Patient's mean age was 59.90 +/- 17.4 years; Acute Physiology and Chronic Health
      Evaluation II score, 17.84 +/- 7.13; 50% were on mechanical ventilation (MV); and
      average ICU stay, 9.40 +/- 9.82 days. Patient's age correlated directly with PS
      (P = .017 when patient was on MV and length of stay >3 days). Acute Physiology
      and Chronic Health Evaluation II greater than 7 correlated with PS (P = .043).
      CONCLUSIONS: Close relatives of patients admitted to the ICU experience a high
      prevalence of PTSD during and after hospitalization. Individual patient factors
      such as severity, age, and being on MV increase the occurrence of PTSD, as well
      as sex and baseline anxiety levels of caregivers. Preventative measures could be
      devised for this particular high-risk population.

PMID- 26197781
TI  - Persistent type III cavity-spilling coronary perforation due to covered stent
      malapposition.
AB  - Coronary perforations are a rare but potentially catastrophic complication of
      percutaneous coronary intervention. We report a rare case of a large cavity
      spilling perforation from the left anterior descending coronary artery into the
      left ventricle, which was successfully treated with a covered stent. However,
      repeating angiography 1 week later demonstrated persistence of the perforation
      due to stent malapposition. 

PMID- 26197779
TI  - The LIFE-Adult-Study: objectives and design of a population-based cohort study
      with 10,000 deeply phenotyped adults in Germany.
AB  - BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has
      recently completed the baseline examination of 10,000 randomly selected
      participants from Leipzig, a major city with 550,000 inhabitants in the east of
      Germany. It is the first study of this kind and size in an urban population in
      the eastern part of Germany. The study is conducted by the Leipzig Research
      Centre for Civilization Diseases (LIFE). Our objective is to investigate
      prevalences, early onset markers, genetic predispositions, and the role of
      lifestyle factors of major civilization diseases, with primary focus on metabolic
      and vascular diseases, heart function, cognitive impairment, brain function,
      depression, sleep disorders and vigilance dysregulation, retinal and optic nerve
      degeneration, and allergies. METHODS/DESIGN: The study covers a main age range
      from 40-79 years with particular deep phenotyping in elderly participants above
      the age of 60. The baseline examination was conducted from August 2011 to
      November 2014. All participants underwent an extensive core assessment programme
      (5-6 h) including structured interviews, questionnaires, physical examinations,
      and biospecimen collection. Participants over 60 underwent two additional
      assessment programmes (3-4 h each) on two separate visits including deeper
      cognitive testing, brain magnetic resonance imaging, diagnostic interviews for
      depression, and electroencephalography. DISCUSSION: The participation rate was 33
      %. The assessment programme was accepted well and completely passed by almost all
      participants. Biomarker analyses have already been performed in all participants.
      Genotype, transcriptome and metabolome analyses have been conducted in subgroups.
      The first follow-up examination will commence in 2016.

PMID- 26197782
TI  - Clock gene polymorphism and scheduling of migration: a geolocator study of the
      barn swallow Hirundo rustica.
AB  - Circannual rhythms often rely on endogenous seasonal photoperiodic timers
      involving 'clock' genes, and Clock gene polymorphism has been associated to
      variation in phenology in some bird species. In the long-distance migratory barn
      swallow Hirundo rustica, individuals bearing the rare Clock allele with the
      largest number of C-terminal polyglutamine repeats found in this species (Q8)
      show a delayed reproduction and moult later. We explored the association between
      Clock polymorphism and migration scheduling, as gauged by light-level
      geolocators, in two barn swallow populations (Switzerland; Po Plain, Italy).
      Genetic polymorphism was low: 91% of the 64 individuals tracked year-round were
      Q7/Q7 homozygotes. We compared the phenology of the rare genotypes with the
      phenotypic distribution of Q7/Q7 homozygotes within each population. In
      Switzerland, compared to Q7/Q7, two Q6/Q7 males departed earlier from the
      wintering grounds and arrived earlier to their colony in spring, while a single
      Q7/Q8 female was delayed for both phenophases. On the other hand, in the Po
      Plain, three Q6/Q7 individuals had a similar phenology compared to Q7/Q7. The
      Swiss data are suggestive for a role of genetic polymorphism at a candidate
      phenological gene in shaping migration traits, and support the idea that Clock
      polymorphism underlies phenological variation in birds. 

PMID- 26197783
TI  - Arctic plant origins and early formation of circumarctic distributions: a case
      study of the mountain sorrel, Oxyria digyna.
AB  - Many plant species comprising the present-day Arctic flora are thought to have
      originated in the high mountains of North America and Eurasia, migrated
      northwards as global temperatures fell during the late Tertiary period, and
      thereafter attained a circumarctic distribution. However, supporting evidence for
      this hypothesis that provides a temporal framework for the origin, spread and
      initial attainment of a circumarctic distribution by an arctic plant is currently
      lacking. Here we examined the origin and initial formation of a circumarctic
      distribution of the arctic mountain sorrel (Oxyria digyna) by conducting a
      phylogeographic analysis of plastid and nuclear gene DNA variation. We provide
      evidence for an origin of this species in the Qinghai-Tibet Plateau of
      southwestern China, followed by migration into Russia c. 11 million yr ago (Ma),
      eastwards into North America by c. 4 Ma, and westwards into Western Europe by c.
      1.96 Ma. Thereafter, the species attained a circumarctic distribution by
      colonizing Greenland from both sides of the Atlantic Ocean. Following the arrival
      of the species in North America and Europe, population sizes appear to have
      increased and then stabilized there over the last 1 million yr. However, in
      Greenland a marked reduction followed by an expansion in population size is
      indicated to have occurred during the Pleistocene. 

PMID- 26197784
TI  - High-performance ultraviolet photodetectors based on solution-grown ZnS nanobelts
      sandwiched between graphene layers.
AB  - Ultraviolet (UV) light photodetectors constructed from solely inorganic
      semiconductors still remain unsatisfactory because of their low electrical
      performances. To overcome this limitation, the hybridization is one of the key
      approaches that have been recently adopted to enhance the photocurrent. High
      performance UV photodetectors showing stable on-off switching and excellent
      spectral selectivity have been fabricated based on the hybrid structure of
      solution-grown ZnS nanobelts and CVD-grown graphene. Sandwiched structures and
      multilayer stacking strategies have been applied to expand effective junction
      between graphene and photoactive ZnS nanobelts. A multiply sandwich-structured
      photodetector of graphene/ZnS has shown a photocurrent of 0.115 mA under
      illumination of 1.2 mWcm(-2) in air at a bias of 1.0 V, which is higher 10(7)
      times than literature values. The multiple-sandwich structure of UV-light sensors
      with graphene having high conductivity, flexibility, and impermeability is
      suggested to be beneficial for the facile fabrication of UV photodetectors with
      extremely efficient performances. 

PMID- 26197785
TI  - Modulation of the Lactobacillus acidophilus La-5 lipidome by different growth
      conditions.
AB  - Probiotics are bacteria used in the food industry due to their potential health
      benefits. In this study, the plasma membrane of the probiotic Lactobacillus
      acidophilus La-5 was investigated using state-of-the-art high-resolution shotgun
      lipidomics. Comparisons of the lipidome of the plasma membrane were done after
      altering the fatty acid composition by supplementing L. acidophilus La-5 with
      saturated, mono-, di- and tri-unsaturated fatty acids during fermentation. The
      plasma membrane with the highest degree of saturation resulted in a lipid
      composition with the highest proportion of cardiolipin (CL) and lowest proportion
      of monolysocardiolipin (MLCL). No significant changes were found for other lipid
      classes. The bacteria grown with di- and tri-unsaturated fatty acids were
      expected to have more unsaturated plasma membranes than bacteria grown with mono
      unsaturated fatty acids. This was also the case for MLCL, but the numbers of
      double bonds for CL were quite similar for these three samples. The results
      indicate that L. acidophilus La-5 possesses a molecular mechanism for remodelling
      and optimizing the fatty acid composition of CL and MLCL species and the molar
      ratio of CL and MLCL. This study contributes new knowledge on the previously
      uninvestigated lipidome of L. acidophilus La-5.

PMID- 26197786
TI  - A Stable Organic pi-Radical of a Zinc(II)-Copper(I)-Zinc(II) Complex of
      Decaphyrin.
AB  - A Zn(II) -Cu(I) -Zn(II) heterotrimetal complex of decaphyrin was synthesized by
      stepwise metalations: metalation of a [46]decaphyrin with Zn(II) ions to produce
      a 46pi decaphyrin bis(Zn(II) ) complex and its subsequent metalation with Cu(II)
      ion. In the second metalation step, it has been shown that Cu(II) ion is reduced
      to a Cu(I) ion in the complex and a dianionic bis(Zn(II) ) containing
      [46]decaphyrin ligand is oxidized to the corresponding monoanionic [45]decaphyrin
      ligand, indicating a non-innocent nature of the decaphyrin ligand. Despite the
      radical nature, the heterotrimetal complex is fairly stable under ambient
      conditions and exhibits almost no intermolecular magnetic interaction, owing to
      extensive delocalization of an unpaired electron in the large pi-conjugated
      circuit of decaphyrin moiety. 

PMID- 26197787
TI  - Observation of vibrational overtones by single-molecule resonant
      photodissociation.
AB  - Molecular ions can be held in a chain of laser-cooled atomic ions by sympathetic
      cooling. This system is ideal for performing high-precision molecular
      spectroscopy with applications in astrochemistry and fundamental physics. Here we
      show that this same system can be coupled with a broadband laser to discover new
      molecular transitions. We use three-ion chains of Ca(+) and CaH(+) to observe
      vibrational transitions via resonance-enhanced multiphoton dissociation detected
      by Ca(+) fluorescence. On the basis of theoretical calculations, we assign the
      observed peaks to the transition from the ground vibrational state, nu=0 to nu=9
      and 10. Our method allows us to track single-molecular events, and it can be
      extended to work with any molecule by using normal mode frequency shifts to
      detect the dissociation. This survey spectroscopy serves as a bridge to the
      precision spectroscopy required for molecular ion control. 

PMID- 26197788
TI  - Phthalimide analogs as probable 15-lipoxygenase-1 inhibitors: synthesis,
      biological evaluation and docking studies.
AB  - BACKGROUND: Recent studies have been explained the role of lipoxygenases (LOX) in
      the origin of cancer. Among the lipoxygenases, the 5-LOX, 12-LOX and 15-LOX are
      more important in the cause of neoplastic disorders. In the present
      investigation, a new series of anticancer agents with 1,3,4-thiadiazole and
      phthalimide substructures were synthesized and their in vitro cytotoxicity was
      evaluated by MTT assay. Moreover, enzyme inhibitory potency was also assessed by
      enzymatic protocol towards 15-LOX-1. Molecular docking was performed to explore
      in silico binding mode of the target compounds. RESULTS: Tested compounds showed
      a better cytotoxic activity against HT29 cell line (colorectal cancer) in
      comparison with other cell lines (PC3: prostate carcinoma; SKNMC: neuroblastoma).
      Unfortunately, all of the tested derivatives rendered lower inhibitory potency
      than quercetin towards 15-LOX-1. Four hydrogen bonds were detected in docking
      studies for compound 4d as the most potent derivative in enzymatic assay.
      CONCLUSIONS: The biological results of reported compounds in this research were
      not so satisfactory. But, further structural modifications are necessary to
      improve the bioactivity of these derivatives.

PMID- 26197789
TI  - New oxymesterone metabolites in human by gas chromatography-tandem mass
      spectrometry and their application for doping control.
AB  - Oxymesterone (17alpha-methyl-4, 17beta-dihydroxy-androst-4-ene-3-one) is one of
      the anabolic androgenic steroids (AAS) banned by the World Anti-Doping Agency
      (WADA). The biotransformation of oxymesterone is performed in vitro by human
      heptocytes and human urinary metabolic profiles are investigated after single
      dose of 20 mg to two adult males as well. Cell cultures and urine samples were
      hydrolyzed by beta-glucuronidase, extracted, and reacted with N-Methyl-N
      trimethylsilyltrifluoroacetamide (MSTFA), ammonium iodide (NH4 I), and
      dithioerythritol. After derivatization, a gas chromatography triple quadruple
      tandem mass spectrometry (GC-MS/MS) using full scan and MS/MS modes was applied.
      The total ion chromatographs of the blank and the positive samples are compared,
      and 7 new metabolites were found. In addition to the well-known 17
      epioxymesterone, oxymesterone is metabolized by 4-ene-reduction, 3-keto
      reduction, 11beta-hydroxylation, and 16xi-hydroxylation. Based on the behavior of
      the MS/MS results of product ion and precursor ion modes, a GC-MS/MS method has
      been developed monitoring these metabolites. The structures of metabolite 2 and 4
      are tentatively identified as 17alpha-methyl-3beta, 17beta-dihydroxy-5alpha
      androstane-4-one and 17alpha-methyl-3alpha, 4xi, 17beta-trihydroxy-5alpha
      androstane, respectively. Detection of oxymesterone using new metabolites M2 and
      M4 can extend the detection window up to 4 days since the parent steroid was not
      detectable. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26197790
TI  - Association of calcium antagonist use with lower hemoglobin levels in
      hemodialysis patients.
AB  - AIM: Objective of the present study was to investigate whether calcium antagonist
      use is associated with lower hemoglobin levels and/or higher erythropoiesis
      stimulating agent (ESA) requirement in hemodialysis patients. METHODS: A total of
      130 adult hemodialysis patients were classified into two groups based on calcium
      antagonist usage for a period of at least 3 months as calcium antagonist users
      and calcium antagonist non-users. The two groups were compared cross-sectionally
      in a retrospective manner in terms of demographics, chronic kidney disease
      aetiologies, Charlson's Comorbidty Index, blood pressure, type of dialysis
      access, interdialytic body weight gain, cardiothoracic index, complete blood
      count, biochemistry, regular medication use and consumption of ESA. All
      independent variables that were different between the groups were subjected to
      logistic regression analysis. Linear regression analysis with dependent variable
      of hemoglobin value was also performed RESULTS: ESA consumption and blood
      pressure were higher, diabetic nephropathy, doxazosin and ACE inhibitor use were
      more frequent, and hemoglobin was lower in the calcium antagonist users. After
      logistic regression analysis, diabetic nephropathy, doxazosin use, ACE inhibitor
      use and lower hemoglobin were associated with calcium antagonist use. After
      lineer regression analysis, Age, BMI, gender, predialysis creatinine value,
      dialysis duration, systolic and diastolic blood pressure, doxazosin use, diabetes
      mellitus and diabetic nephropathy were not related with hemoglobin value. But,
      higher amount of ESA consumption, ACE inhibitor use and calcium antagonist use
      were significantly associated with lower hemoglobin value. CONCLUSION: CA use was
      associated with lower hemoglobin levels in our hemodialysis patient population.

PMID- 26197791
TI  - Recent advances in prostate cancer: diagnosis, patient selection and minimally
      invasive treatment.

PMID- 26197796
TI  - Quality of life and functional evaluation in patients with tongue base tumors
      treated exclusively with transoral robotic surgery: A 1-year follow-up study.
AB  - BACKGROUND: To evaluate quality-of-life (QoL), swallowing and voice in patients
      with base of tongue (BOT) tumors treated with transoral robotic surgery (TORS)
      alone without any adjuvant treatment. METHODS: The study was a prospective,
      single-center cohort trial. Swallowing, QoL and voice were evaluated in 13
      patients with T1 or T2 oropharyngeal carcinomas of the BOT. Patients underwent
      evaluation using the following: a dysphagia score (DS); fiberoptic endoscopic
      evaluation-of-swallowing with the penetration aspiration scale (PAS); the MD
      Anderson Dysphagia Inventory (MDADI); and the Voice Handicap Index-10 (VHI-10).
      RESULTS: Subjective (DS) and objective (PAS) evaluation of swallowing produced
      mean scores of 1.08, 2.23 and 1.46 before surgery and at 6 and 12 months after
      surgery, respectively, for both tests. A significant difference was found when
      comparing DS and PAS data at baseline and 6 months after surgery; while no
      difference was observed between the baseline and 12 months after surgery. The
      mean values of the MDADI and VHI scores recorded before surgery, and at 6 and 12
      months after surgery did not show any statistical difference. CONCLUSIONS:
      Objective swallowing deterioration in the first 6 months after TORS alone for BOT
      tumors was possible, but complete recovery of deglutition was observed within 12
      months. No changes were reported in the patients' self-perceived status of
      swallowing and voice dysfunction, and related QoL after 1 year.

PMID- 26197797
TI  - A new diketopiperazine derivative from a deep sea-derived Streptomyces sp. SCSIO
      04496.
AB  - A new diketopiperazine (DKP) derivative, (6R,3Z)-3-benzylidene-6-isobutyl-1
      methyl piperazine-2,5-dione (1), as well as five known DKPs 2-6 was isolated from
      a deep sea-derived Streptomyces sp. SCSIO 04496. The structure of 1 was
      elucidated using a combination of 1D and 2D NMR, HR-ESI-MS and chiral-phase HPLC
      techniques. Compounds 1-6 did not show cytotoxic activity at a concentration of
      100 MUM in bioactivity assay.

PMID- 26197798
TI  - Immediate and distal effects of the good behavior game.
AB  - The Good Behavior Game (GBG) has been demonstrated to reduce disruptive student
      behavior during implementation. The effects of playing the GBG on disruption
      immediately before and after the GBG are unknown. The current study evaluated the
      effects of the GBG on disruption in 5 kindergarten classes immediately before,
      during, and after GBG implementation. The GBG reduced disruption during
      implementation but did not affect rates of disruption during activity periods
      that preceded or followed the GBG. 

PMID- 26197799
TI  - Planned Parenthood accuses anti-abortion group of "corporate espionage" for
      promoting misleading video.

PMID- 26197800
TI  - Ovarian-type epithelial tumours of the testis: immunohistochemical and molecular
      analysis of two serous borderline tumours of the testis.
AB  - Tumours of ovarian-epithelial type of the testis, including serous borderline
      tumours, represent very rare entities. They are identical to the surface
      epithelial tumours of the ovary and have been reported in patients from 14 to 68
      years of age. We describe two cases of a 46- and a 39-year old man with
      incidental findings of intratesticular masses of the left respectively right
      testis. Under the assumption of a malignant testicular tumour the patients were
      subjected to inguinal orchiectomy. Histologically, the tumours were identical to
      their ovarian counterparts: They showed a cystic configuration with a fibrous
      wall and irregular papillary structures lined by partially multistratified
      columnar cells and areas of hobnail cells. Furthermore, there was mild
      cytological atypia with a proliferative activity of below 5% as proved by Ki67
      staining; mitoses could not be detected. Immunohistochemically, the tumour cells
      displayed expression of pan-cytokeratin AE3, progesterone receptor, Wilms' tumour
      protein (WT1), and PAX8 (Paired box gene 8). Estrogen receptor was expressed in
      one case. Octamer-binding transcription factor-4 (OCT4), calretinin,
      thrombomodulin, and D2-40 were not expressed. Mutation testing of BRAF revealed a
      BRAF V600E mutation in one case, while testing for KRAS mutations proved to be
      negative in both. The BRAF mutated tumour showed strong cytosolic and membranous
      positivity for B-Raf also on immunohistochemical analysis. Comparative genomic
      hybridization of one case could not reveal any chromosomal aberrations.

PMID- 26197801
TI  - A Cost-Effectiveness Analysis of Blended Versus Face-to-Face Delivery of Evidence
      Based Medicine to Medical Students.
AB  - BACKGROUND: Blended learning describes a combination of teaching methods, often
      utilizing digital technologies. Research suggests that learner outcomes can be
      improved through some blended learning formats. However, the cost-effectiveness
      of delivering blended learning is unclear. OBJECTIVE: This study aimed to
      determine the cost-effectiveness of a face-to-face learning and blended learning
      approach for evidence-based medicine training within a medical program. METHODS:
      The economic evaluation was conducted as part of a randomized controlled trial
      (RCT) comparing the evidence-based medicine (EBM) competency of medical students
      who participated in two different modes of education delivery. In the traditional
      face-to-face method, students received ten 2-hour classes. In the blended
      learning approach, students received the same total face-to-face hours but with
      different activities and additional online and mobile learning. Online activities
      utilized YouTube and a library guide indexing electronic databases, guides, and
      books. Mobile learning involved self-directed interactions with patients in their
      regular clinical placements. The attribution and differentiation of costs between
      the interventions within the RCT was measured in conjunction with measured
      outcomes of effectiveness. An incremental cost-effectiveness ratio was calculated
      comparing the ongoing operation costs of each method with the level of EBM
      proficiency achieved. Present value analysis was used to calculate the break-even
      point considering the transition cost and the difference in ongoing operation
      cost. RESULTS: The incremental cost-effectiveness ratio indicated that it costs
      24% less to educate a student to the same level of EBM competency via the blended
      learning approach used in the study, when excluding transition costs. The sunk
      cost of approximately AUD $40,000 to transition to the blended model exceeds any
      savings from using the approach within the first year of its implementation;
      however, a break-even point is achieved within its third iteration and relative
      savings in the subsequent years. The sensitivity analysis indicates that
      approaches with higher transition costs, or staffing requirements over that of a
      traditional method, are likely to result in negative value propositions.
      CONCLUSIONS: Under the study conditions, a blended learning approach was more
      cost-effective to operate and resulted in improved value for the institution
      after the third year iteration, when compared to the traditional face-to-face
      model. The wider applicability of the findings are dependent on the type of
      blended learning utilized, staffing expertise, and educational context.

PMID- 26197803
TI  - Review of Preoperative Carbohydrate Loading.
AB  - Preoperative carbohydrate-containing clear liquids (usually composed of
      approximately 12% carbohydrate predominantly in maltodextrin form) have provided
      benefits for the surgical population and further have been included in the
      Enhanced Recovery After Surgery (ERAS) Society's recommendations as part of a
      multimodal approach to reduce surgical patients' length of stay and complication
      rates. Carbohydrate metabolism is greatly affected by the fed state, which is
      activated by preoperative carbohydrate fluids given up to 2 hours prior to
      surgery in contrast to the traditional midnight preoperative fast. Carbohydrate
      rich fluids have been proven to enhance patient comfort prior to surgery and have
      been theorized to reduce insulin resistance, reducing patient catabolism, with a
      positive impact on perioperative glucose control and muscle preservation. This
      practice is further hypothesized to support the ERAS goals of reducing both
      complication rate and length of stay. Preoperative carbohydrate fluid loading is
      difficult to prove, as the degree of surgical procedure and postoperative
      pathways are likely more reflective of patient outcome. The use of carbohydrate
      loading protocols warrants further adequately blinded, placebo-controlled
      studies, including the use of variable surgical techniques, reproduction of the
      hyperinsulinemic euglycemic technique measurements, investigation of ideal
      carbohydrate fluid composition, and the use of similar surgeries in comparison.
      Preoperative carbohydrate loading is just one of the many strategies linked to
      the success of ERAS protocols. 

PMID- 26197802
TI  - Folate levels modulate oncogene-induced replication stress and tumorigenicity.
AB  - Chromosomal instability in early cancer stages is caused by replication stress.
      One mechanism by which oncogene expression induces replication stress is to drive
      cell proliferation with insufficient nucleotide levels. Cancer development is
      driven by alterations in both genetic and environmental factors. Here, we
      investigated whether replication stress can be modulated by both genetic and non
      genetic factors and whether the extent of replication stress affects the
      probability of neoplastic transformation. To do so, we studied the effect of
      folate, a micronutrient that is essential for nucleotide biosynthesis, on
      oncogene-induced tumorigenicity. We show that folate deficiency by itself leads
      to replication stress in a concentration-dependent manner. Folate deficiency
      significantly enhances oncogene-induced replication stress, leading to increased
      DNA damage and tumorigenicity in vitro. Importantly, oncogene-expressing cells,
      when grown under folate deficiency, exhibit a significantly increased frequency
      of tumor development in mice. These findings suggest that replication stress is a
      quantitative trait affected by both genetic and non-genetic factors and that the
      extent of replication stress plays an important role in cancer development.

PMID- 26197804
TI  - TNF-a mediated inflammatory macrophage polarization contributes to the
      pathogenesis of steroid-induced osteonecrosis in mice.
AB  - The phenotypic polarization of macrophages are involved in steroid-induced
      osteonecrosis (ON). This study tried to investigate the detrimental and
      beneficial roles of M1/M2 macrophages associated with TNF-a in ON. Mice ON model
      was induced by the injection of methylprednisolone. After that, flow cytometry
      technique, immunohistochemistry, immunofluorescence, ELISA, and RT-PCR methods
      were used to investigate the expression pattern of macrophages and the expression
      of inflammatory cytokines. During the progression of ON, massive chronic
      inflammatory cells infiltrated into the necrotic zone, represented by the
      infiltration of macrophages. In the early stage of ON, there was high TNF-a
      activity; and a large population of M1 macrophages infiltrated into the necrotic
      zone. On the contrary, the expression of TNF-a gradually decreased;
      simultaneously, a larger M2 cell population presented in the necrotic zone in the
      late stage of ON. The increased M2 macrophages could be beneficial for resolving
      inflammation and promoting tissue repair, confirmed by the histologic findings of
      appositional new bone formation around the necrotic bone. Thus, it showed that
      TNF-a-mediated alteration of M1/M2 macrophage polarization contributed to the
      pathogenesis of steroid-induced osteonecrosis. M1-polarized macrophages appeared
      to be disruptive in the early stage of ON, while M2-polarized macrophages played
      an important role in the late stage during the pathogenesis of ON. 

PMID- 26197806
TI  - Large bowel obstruction resulting from bladder transitional cell carcinoma
      metastasis: a common cancer presenting in an uncommon manner.
AB  - Transitional cell carcinoma (TCC) and large bowel obstructions are both common
      disease processes typically considered unrelated. Presented below is the case of
      a 49-year-old male with a large bowel obstruction caused by a bladder TCC
      metastasis. One year prior to large bowel obstruction presentation, the patient
      had a T2, Grade III TCC of the bladder with no nodal involvement or metastasis,
      which was removed via radical cystoprostatectomy. This case serves as a reminder
      that cancer, despite common pathogenesis patterns, can present in atypical ways. 

PMID- 26197805
TI  - The brain's conversation with itself: neural substrates of dialogic inner speech.
AB  - Inner speech has been implicated in important aspects of normal and atypical
      cognition, including the development of auditory hallucinations. Studies to date
      have focused on covert speech elicited by simple word or sentence repetition,
      while ignoring richer and arguably more psychologically significant varieties of
      inner speech. This study compared neural activation for inner speech involving
      conversations ('dialogic inner speech') with single-speaker scenarios ('monologic
      inner speech'). Inner speech-related activation differences were then compared
      with activations relating to Theory-of-Mind (ToM) reasoning and visual
      perspective-taking in a conjunction design. Generation of dialogic (compared with
      monologic) scenarios was associated with a widespread bilateral network including
      left and right superior temporal gyri, precuneus, posterior cingulate and left
      inferior and medial frontal gyri. Activation associated with dialogic scenarios
      and ToM reasoning overlapped in areas of right posterior temporal cortex
      previously linked to mental state representation. Implications for understanding
      verbal cognition in typical and atypical populations are discussed. 

PMID- 26197808
TI  - Bioinformatics methods in drug repurposing for Alzheimer's disease.
AB  - Alarming epidemiological features of Alzheimer's disease impose curative
      treatment rather than symptomatic relief. Drug repurposing, that is reappraisal
      of a substance's indications against other diseases, offers time, cost and
      efficiency benefits in drug development, especially when in silico techniques are
      used. In this study, we have used gene signatures, where up- and down-regulated
      gene lists summarize a cell's gene expression perturbation from a drug or
      disease. To cope with the inherent biological and computational noise, we used an
      integrative approach on five disease-related microarray data sets of hippocampal
      origin with three different methods of evaluating differential gene expression
      and four drug repurposing tools. We found a list of 27 potential anti-Alzheimer
      agents that were additionally processed with regard to molecular similarity,
      pathway/ontology enrichment and network analysis. Protein kinase C, histone
      deacetylase, glycogen synthase kinase 3 and arginase inhibitors appear
      consistently in the resultant drug list and may exert their pharmacologic action
      in an epidermal growth factor receptor-mediated subpathway of Alzheimer's
      disease. 

PMID- 26197807
TI  - Protein: A nutrient in focus.
AB  - Protein is an essential component of a healthy diet and is a focus of research
      programs seeking to optimize health at all stages of life. The focus on protein
      as a nutrient often centers on its thermogenic and satiating effect, and when
      included as part of a healthy diet, its potential to preserve lean body mass. A
      growing body of literature, including stable isotope based studies and longer
      term dietary interventions, suggests that current dietary protein recommendations
      may not be sufficient to promote optimal muscle health in all populations. A
      protein intake moderately higher than current recommendations has been widely
      endorsed by many experts and working groups and may provide health benefits for
      aging populations. Further, consuming moderate amounts of high-quality protein at
      each meal may optimally stimulate 24-h muscle protein synthesis and may provide a
      dietary platform that favors the maintenance of muscle mass and function while
      promoting successful weight management in overweight and obese individuals.
      Dietary protein has the potential to serve as a key nutrient for many health
      outcomes and benefits might be increased when combined with adequate physical
      activity. Future studies should focus on confirming these health benefits from
      dietary protein with long-term randomized controlled studies. 

PMID- 26197810
TI  - Stent graft perforation of a frozen elephant prosthesis: does design matter?
AB  - The frozen elephant procedure, as a hybrid method to treat aortic pathologies
      involving the aortic arch and the proximal descending aorta, has become an
      accepted treatment option. We report two late fractures of the nitinol stents of
      the endograft of an early frozen elephant trunk prosthesis. One patient suffered
      from a tear of the woven polyester fabric, causing a Type III endoleak and rapid
      progression of the existing descending aortic aneurysm. The patient received
      replacement of the descending aorta. The second patient showed a fracture of a
      nitinol stent without further complications during follow-up. 

PMID- 26197809
TI  - Empirical comparison of structure-based pathway methods.
AB  - Multiple methods have been proposed to estimate pathway activities from
      expression profiles, and yet, there is not enough information available about the
      performance of those methods. This makes selection of a suitable tool for pathway
      analysis difficult. Although methods based on simple gene lists have remained the
      most common approach, various methods that also consider pathway structure have
      emerged. To provide practical insight about the performance of both list-based
      and structure-based methods, we tested six different approaches to estimate
      pathway activities in two different case study settings of different
      characteristics. The first case study setting involved six renal cell cancer data
      sets, and the differences between expression profiles of case and control samples
      were relatively big. The second case study setting involved four type 1 diabetes
      data sets, and the profiles of case and control samples were more similar to each
      other. In general, there were marked differences in the outcomes of the different
      pathway tools even with the same input data. In the cancer studies, the results
      of a tested method were typically consistent across the different data sets, yet
      different between the methods. In the more challenging diabetes studies, almost
      all the tested methods detected as significant only few pathways if any. 

PMID- 26197811
TI  - Generalized ischaemia in type A aortic dissections predicts early surgical
      outcomes only.
AB  - OBJECTIVES: In patients with acute type A aortic dissection (aTAAD), early post
      surgical outcomes are largely influenced by preoperative conditions, specifically
      localized or generalized ischaemia. Such states are reflected in the recent Penn
      classification. Our aim was to determine the impact of preoperative ischaemia (by
      Penn class) on in-hospital and long-term mortality. METHODS: All consecutive
      patients (n = 341) surgically treated for aTAAD between 1998 and 2014 were
      recruited for a retrospective observational study. Parameters impacting in
      hospital and long-term mortality were identified through univariable and
      multivariable analyses. RESULTS: In-hospital mortality rates by Penn class were
      as follows: Class Aa, 11%; Class Ab, 14%; Class Ac, 42% and Class Abc, 29%. Both
      Ac [odds ratio (OR) = 4.4; 95% confidence interval (CI), 1.92-9.80] and Abc (OR =
      3.72; 95% CI, 1.26-10.99) classifications independently predicted in-hospital
      mortality, as did cardiopulmonary bypass time (OR = 1.01; 95% CI, 1.00-1.01).
      Relative to Class Aa patients, survival did not differ significantly in Class Ac
      and Abc subsets (log-rank P = 0.365 and P = 0.716, respectively), once 30-day
      postoperative deaths were excluded. The leading cause of late mortality was
      cardiac failure or myocardial infarction (29%), followed by aortic rupture (25%).
      Independent predictors of long-term mortality after aTAAD were age [hazard ratio
      (HR) = 1.08; 95% CI, 1.05-1.10] and supracoronary replacement graft (HR = 2.27;
      95% CI, 1.1-4.75). CONCLUSIONS: Penn classes Ac and Abc were identified as an
      independent risk factor for in-hospital mortality, whereas neither Penn class nor
      organ-specific ischaemia significantly impacted long-term survival. Regardless of
      ischaemic manifestations at presentation, the prognosis of patients surviving
      both surgery and early postoperative period proved acceptable.

PMID- 26197813
TI  - Intracanal molar barometric pressure differentials at simulated altitude
      conditions - proof of concept study.
AB  - AIM: To evaluate whether objective data could be obtained regarding internal
      pressure conditions of a molar tooth with canals prepared but not filled exposed
      to reduced barometric pressures that could be experienced by aircrew.
      METHODOLOGY: The root canals of five mandibular molars were prepared but not
      filled. Root apices were sealed with a resin-modified glass-ionomer liner and
      root surfaces sealed with a dental adhesive. The sealed root surfaces were then
      coated with a polyvinylsiloxane (PVS) adhesive and the teeth inserted into
      cylinders of PVS impression material to the level of the cervical enamel
      junction. Barometric pressure transducers were placed in the pulp chambers with
      the endodontic access sealed with cotton and a provisional restoration. The
      specimens were then subjected to a manually controlled, atmospheric altitude
      challenge consisting of a slow ascent and descent to a simulated 25 000 feet
      above sea level followed by a rapid altitude climb and descent. The real-time
      difference between intracanal and simulated atmospheric pressures were recorded
      and correlated (Pearson's, P = 0.05). RESULTS: No tooth material fractured, and
      there was no failure of the provisional restorations. Barometric pressures inside
      the closed prepared molar canals and the ambient atmospheric pressure were found
      to correlate (r(2)  = 0.97-0.99; P < 0.0001), but pressure equalization lags were
      observed. However, no differences greater than six pounds per square inch (310
      torr) were noted. CONCLUSION: This pilot study established a protocol that
      demonstrated that objective data regarding barometric pressures within the
      prepared canals of molars can be obtained at simulated altitude conditions.

PMID- 26197812
TI  - Functional capacity and heart rate response: associations with nocturnal
      hypertension.
AB  - BACKGROUND: Absences of normative, 10-20 % declines in blood pressure (BP) at
      night, termed nocturnal non-dipping, are linked to increased cardiovascular
      mortality risks. Current literature has linked these absences to psychological
      states, hormonal imbalance, and disorders involving hyper-arousal. This study
      focuses on evaluating associations between nocturnal non-dipping and indices of
      functional cardiac capacity and fitness. METHODS: The current study was a cross
      sectional evaluation of the associations between physical capacity variables e.g.
      Metabolic Equivalent (MET) and Maximum Heart Rate (MHR), Heart rate reserve
      (HRR), and degree of reduction in nocturnal systolic blood pressure (SBP) or
      diastolic blood pressure (DBP), also known as 'dipping'. The study sample
      included 96 cardiac patient participants assessed for physical capacity and
      ambulatory blood pressure monitoring. In addition to evaluating differences
      between groups on nocturnal BP 'dipping', physical capacity, diagnoses, and
      medications, linear regression analyses were used to evaluate potential
      associations between nocturnal SBP and DBP 'dipping', and physical capacity
      indices. RESULTS: 45 males and 14 females or 61.5 % of 96 consented participants
      met criteria as non-dippers (<10 % drop in nocturnal BP). Although non-dippers
      were older (p = .01) and had a lower maximum heart rate during the Bruce stress
      test (p = .05), dipping was only significantly associated with Type 2 Diabetes co
      morbidity and was not associated with type of medication. Within separate linear
      regression models controlling for participant sex, MHR (beta = 0.26, p = .01,
      R(2) = .06), HRR (beta = 0. 19, p = .05, R(2) = .05), and METs (beta = 0.21, p =
      .04, R(2) = .04) emerged as significant but small predictors of degree of
      nighttime SBP dipping. Similar relationships were not observed for DBP.
      CONCLUSIONS: Since the variables reflecting basic heart function and fitness (MHR
      and METs), did not account for appreciable variances in nighttime BP, nocturnal
      hypertension appears to be a complex, multi-faceted phenomena.

PMID- 26197814
TI  - A care-bundles approach to improving standard of care in AECOPD admissions:
      results of a national project.
AB  - This report describes a care bundles implementation project for COPD undertaken
      during 2013 in England and Wales. High-level data were collected on outcomes of
      care for 11 748 patients admitted with an acute exacerbation of COPD (AECOPD).
      Patient-level data on processes and outcomes of care were collected on 3272 COPD
      admissions, among which 1174 bundles were delivered. Analysis demonstrated a
      statistically significant reduction in mortality and length of hospital stay from
      some bundle elements. Outcomes, including bundle completion rates, were better
      when specialist respiratory review occurred. The results support wider use of
      care bundles for AECOPD. 

PMID- 26197815
TI  - British Thoracic Society community-acquired pneumonia care bundle: results of a
      national implementation project.
AB  - In 2013, 16 U.K. hospital trusts participated in a quality improvement programme
      involving implementation of a community-acquired pneumonia (CAP) care bundle.
      High-level data were collected on 14,962 patients admitted with CAP; bundle
      implementation increased from 1% in October 2012 to 20% by September 2013.
      Analysis of patient-level data on 2118 adults (median age 75.3 years) found that
      in the bundle-implementation group, significantly more patients received
      antibiotics within 4 h of admission (adjusted OR 1.52, 95% CI 1.08 to 2.14,
      p=0.016) and 30-day inpatient mortality was lower (8.8% vs. 13.6%; adjusted OR
      0.59, 95% CI 0.37 to 0.95, p=0.03).

PMID- 26197816
TI  - Parasternal electromyography to determine the relationship between patient
      ventilator asynchrony and nocturnal gas exchange during home mechanical
      ventilation set-up.
AB  - INTRODUCTION: Patient-ventilator asynchrony (PVA) can adversely affect the
      successful initiation of non-invasive home mechanical ventilation (HMV). The aim
      of this observational study was to quantify the prevalence of PVA during
      initiation of HMV and to determine the relationship between PVA and nocturnal gas
      exchange. METHOD: Type and frequency of PVA were measured by surface parasternal
      intercostal muscle electromyography, thoracoabdominal plethysmography and mask
      pressure during initiation of HMV. Severe PVA was defined, as previously, as
      asynchrony affecting >=10% of breaths. RESULTS: 28 patients (18 male) were
      enrolled aged 61+/-15 years and with a body mass index of 35+/-9 kg/m(2).
      Underlying diagnoses were neuromuscular disease with or without chest wall
      disease (n=6), obesity related chronic respiratory failure (n=12) and COPD
      (n=10). PVA was observed in all patients with 79% of patients demonstrating
      severe PVA. Triggering asynchrony was most frequent, observed in 24% (IQR: 11
      36%) of breaths, with ineffective efforts accounting for 16% (IQR: 4-24%). PVA
      types were similar between disease groups, with the exception of auto-triggering,
      which was higher in patients with COPD (12% (IQR: 6-26%)). There was no
      correlation observed between PVA and time spent with oxygen saturations <=90%,
      mean oxygen saturations or transcutaneous carbon dioxide levels during overnight
      ventilation. CONCLUSIONS: Severe PVA was identified in the majority of patients,
      irrespective of pathophysiological disease state. This was not associated with
      ineffective ventilation as evidenced by gas exchange.

PMID- 26197817
TI  - Minimum volume standards in German hospitals: do they get along with procedure
      centralization? A retrospective longitudinal data analysis.
AB  - BACKGROUND: Compliance with minimum volume standards for specific procedures
      serves as a criterion for high-quality patient care. International experiences
      report a centralization of the respective procedures. In Germany, minimum volume
      standards for hospitals were introduced in 2004 for 5 procedures (complex
      esophageal and pancreatic interventions; liver, kidney and stem cell
      transplantations), in 2006 total knee replacement was added. This study explores
      whether any centralization is discernible for these procedures in Germany.
      METHODS: A retrospective longitudinal analysis of secondary data serves to
      determine a possible centralization of procedures from the system perspective.
      Centralization means that over time, fewer hospitals perform the respective
      procedure, the case volume in high-volume hospitals increases together with their
      percentage of the annual total case volume, and the case volume in low-volume
      hospitals decreases together with their percentage of the annual total case
      volume. Using data from the mandatory hospital quality reports for the years
      2006, 2008 and 2010 we performed Kruskal Wallis and chi-square tests to evaluate
      potential centralization effects. RESULTS: No centralization was found for any of
      the six types of interventions over the period from 2006 to 2010. The annual case
      volume and the number of hospitals performing interventions rose at differing
      rates over the 5-year period depending on the type of intervention. Seven percent
      of esophagectomies and 14% of pancreatectomies are still performed in hospitals
      with less than 10 interventions per year. CONCLUSIONS: For the purpose of further
      centralization of interventions it will be necessary to first analyze and then
      appropriately address the reasons for non-compliance from the hospital and
      patient perspective.

PMID- 26197819
TI  - Current Resources for Evidence-Based Practice, July/August 2015.

PMID- 26197818
TI  - A cross-sectional analysis of perinatal depressive symptoms among Punjabi
      speaking women: are they at risk?
AB  - BACKGROUND: Depression is the leading cause of disability for childbearing women.
      We examined three specific research questions among Punjabi-speaking women
      residing in the Fraser Health Authority: 1) What are the prevalence rates of
      prenatal depressive symptoms? 2) Do Punjabi-speaking women have a higher
      likelihood of reporting depressive symptoms compared to English-speaking women
      after controlling for age, level of education and financial worries, and 3) Given
      the same level of exposure to level of education and financial worries, do
      Punjabi-speaking women have the same likelihood of reporting depressive symptoms?
      METHODS: Data originated from the Fraser Health Authority prenatal registration
      database consisting of pregnant women (n = 9684) who completed a prenatal
      registration form between June 2009 and August 2010; 9.1 % indicated speaking
      Punjabi. The Whooley Depression Screen measured depressive symptoms. Chi-square
      tests and logistic multiple regression were used to examine the rates of
      reporting depressive symptoms among Punjabi-speaking women compared to English
      speaking women. RESULTS: Punjabi-speaking women are at a higher risk for
      perinatal depressive symptoms. Women needing an interpreter were more likely to
      report prenatal depressive symptoms compared to English-speaking women. All
      registrants who reported financial worries had four and a half times the odds of
      reporting depressive symptoms. The impact of financial worries was significantly
      greater in the English-speaking women compared to the Punjabi-speaking women
      needing an interpreter. CONCLUSION: Using an established screening device,
      Punjabi-speaking women were found to be at higher risk for prenatal depressive
      symptoms.

PMID- 26197820
TI  - Giant Caseous Calcification on Tricuspid Annulus Mimicking Cardiac Metastasis in
      a Patient with Colon Cancer.

PMID- 26197821
TI  - [Surgical Treatment for Mycotic Aortic Aneurysms].
AB  - Mycotic aortic aneurysms are relatively rare. Diagnosis and treatment may
      sometimes be difficult. We have treated 5 cases of mycotic aortic aneurysms in
      our institution. The patients were 4 males and 1 female with a mean age of 65.6+/
      16.7 years old. All patients had vascular diseases and complained of fever.
      Preoperative blood cultures were positive in 4 cases. The strategy for treatment
      of mycotic aortic aneurysms consisted of removal of infective focuses as much as
      possible and revascularization using an artificial graft combined with
      omentopexy. Administration of antibiotics was continued for 6 months. All
      patients have been alive without recurrence of infections for a mean period of
      22.6 months, which was considered to be an acceptable result. Artificial graft
      replacement combined with omentopexy and long-term administration of antibiotics
      is suggested to be useful for the treatment of mycotic aortic aneurysms. 

PMID- 26197822
TI  - [Association Between the pH and Clinicopathological Characteristics of Lung
      Cancer Tissue].
AB  - Recent studies have shown that cancer cells surviving in a microenvironment
      characterized by hypoxia, low pH, and low glucose level have an ability to adapt
      to the adverse conditions. We measured the pH in the central tumor area of
      primary lung cancer, and evaluated its association with clinicopathological
      factors. There was a negative correlation between the tumor size and pH;with an
      increase in the tumor size, the pH decreased. Cancer cells grow at a markedly low
      pH compared with the physiological environment. There is a possibility that this
      low pH is a microenvironment that is appropriate rather than adverse for the
      growth and development of cancer cells. 

PMID- 26197823
TI  - [Intraoperative Endoscopic Evaluation of the Aortic Valve in Aortic Valve
      Repair].
AB  - This report discusses intraoperative endoscopic evaluation of the aortic valve
      performed in 2 cases of aortic valve repair. The "direct" or real image by the
      endoscopy helped to confirm the preoperatively-known lesion and even to detect a
      new legion which was not detected preoperatively. The endoscopy also enabled the
      evaluation of the aortic valve under the pressure-loaded condition without
      releasing the aortic clamp. Postoperative aortic regurgitation was grade I or
      less in both cases, although it progressed to grade II at 1 year in case 2.
      Echocardiographic parameters demonstrated no change in the size of the aortic
      root configuration for 8 and 5 years in case 1 and case 2, respectively.
      Intraoperative aortic endoscopy was useful to define the pathogenesis of aortic
      regurgitation and to evaluate the cusp repair procedures, which may contribute to
      a good mid-term result of aortic valve repair. 

PMID- 26197824
TI  - [Graft Replacement for Adult Aortic Coarctation].
AB  - Case 1:a 47-year-old woman who complained of sweating, finger tremor, and chest
      pain was diagnosed with coarctation of the aorta and hyperthyroidism. She had
      been diagnosed with hypertension at 25 years of age but had not undergone further
      examination. Graft replacement was performed without cardiopulmonary or temporary
      bypass. Case 2:a 30-year-old woman was diagnosed with coarctation during
      infertility treatment. Although health screening had revealed hypertension 8
      years previously, no further assessment took place. She underwent graft
      replacement with partial cardiopulmonary bypass. In both cases, we conducted a
      clamp test to decide whether cardiopulmonary or partial bypass was necessary for
      graft replacement. Blood pressure discrepancy between upper and lower extremities
      disappeared immediately after surgery, and no ischemic complications were
      observed. Hypertension in young adults should prompt further scrutiny for
      anatomical disorders such as coarctation. A clamp test is considered helpful
      regarding the surgical approach to graft replacement for coarctation. 

PMID- 26197825
TI  - [Post Fenestrated Thoracic Empyema with Broncopleural Fistula, Healed
      Successfully without Plombage].
AB  - A 60-year-old man was performed right middle and lower bilobectomy. High fever
      was observed on the 17th postoperative day and the patient was diagnosed as
      having empyema with bronchopleural fistula(BPF). Chest tube drainage and
      antibiotics were started followed by open window thoracotomy on the 61st
      postoperative day. The repetition of closing package procedure was done daily or
      every other day. BPF was successfully covered by good granulation and was healed
      6 months after open thoracotomy. The empyema cavity gradually decreased in size,
      and was completely epithelized 1 year after fenestration. Usually, the treatment
      of empyema with BPF is surgical treatment such as muscle flap plombage, following
      open window thoracotomy. But if the fistula is small and the infection is
      controlled effectively non-surgical treatment following open window thoracotomy
      is potentially useful way to cure the empyema with BPF. 

PMID- 26197826
TI  - [Two-staged Hybrid Repair for Extensive Aortic Aneurysm;Report of a Case].
AB  - A 74-year-old woman progressed to extensive aortic aneurysm after 2 years and 6
      months from onset of type B dissection. A computed tomography scan revealed
      aortic aneurysm from ascending aorta to Th12 level of descending aorta. Her
      appearance was very frailty. Therefore, we performed 2-staged hybrid repair for
      this case. First, surgical total arch replacement with elephant trunk via median
      sternotomy was performed. On the 47th days after the 1st operation, thoracic
      endovascular aortic repair was performed. The spinal drainage was done for spinal
      cord protection. Postoperative course was uneventful without any complications.
      Considering a surgical stress, 2-staged hybrid repair using a stent graft was
      less-invasive than 1 staged graft replacement. 

PMID- 26197827
TI  - [Right Atrial Rupture due to Blunt Trauma;Report of a Case].
AB  - The survival rate of cardiac rupture due to blunt trauma is generally low. We
      report a case of surgical treatment of blunt cardiac trauma. A 55-year-old man
      was admitted to our hospital for blunt trauma due to a car accident. His
      hemodynamics was compromised due to cardiac tamponade. The patient underwent
      pericardial drainage by small subxiphoid incision. Although about 400 ml of blood
      was evacuated, hemorrhage was still continuing. After full sternotomy, we found a
      3 mm tear in the right atrial appendage and sutured it easily without
      cardiopulmonary bypass. The patient recovered uneventfully and was discharged on
      the 10th postoperative day. He is now leading a normal life. 

PMID- 26197828
TI  - [Experience of Mitral Valve Replacement Using a Pulmonary Autograft (Ross II
      Operation) in an Infant;Report of a Case].
AB  - A 24-day-old boy suddenly developed progressive heart failure and was transported
      to our hospital. Echocardiography showed massive mitral regurgitation due to
      chordal rupture. Mitral valve repair was performed at 28 days of life, but
      postoperative valvular function was not satisfactory. A mechanical valve was
      implanted in the supra-annular position at 37 days of life. Two months after
      valve replacement, the mechanical valve was suddenly stuck. Emergent redo valve
      replacement was performed, but the prosthetic valve became stuck again 2 months
      after the 3rd operation, despite sufficient anti-coagulation therapy. At the 4th
      operation (6 months after birth), we implanted a pulmonary autograft in the
      mitral position instead of another mechanical valve in an emergent operation. The
      right ventricular outflow tract was reconstructed with a valved conduit. A
      postoperative catheter examination, which was performed 1 year after the Ross II
      operation, showed mild mitral stenosis with no regurgitation. Previous reports of
      Ross II operations in infants are rare and long-term results are unknown.
      However, we advocate that this procedure should be a rescue operation for mitral
      valve dysfunction in the early period of infants. 

PMID- 26197829
TI  - [Pannus Formation Six-years after Aortic and Mitral Valve Replacement with Tissue
      Valves;Report of a Case].
AB  - A 77-year-old man presented with exertional dyspnea. He had undergone aortic and
      mitral valve replacement with tissue valves 6-years earlier. The patient's
      hemoglobin level was 9.8 g/dl and serum aspartate aminotransferase (70 mU/ml) and
      lactate dehydrogenase (1,112 mU/ml) were elevated. Echocardiography revealed
      stenosis of the prosthetic valve in the aortic position with peak flow velocity
      of 3.8 m/second and massive mitral regurgitation. The patient underwent repeat
      valve replacement. Pannus formation around both implanted valves was observed.
      The aortic valve orifice was narrowed by the pannus, and one cusp of the
      prosthesis in the mitral position was fixed and caused the regurgitation, but
      they were free from cusp laceration or calcification. The patient's postoperative
      course was uneventful, and he continues to do well 14 months after surgery. 

PMID- 26197830
TI  - [Cor Triatriatum Diagnosed in Adulthood;Report of a Case].
AB  - A 64-years-old man had cor triatriatum (Lucas-Schmidt type I A) with severe
      mitral regurgitation and atrial fibrillation. We perfomed resection of the
      anomalous septum between the accessory chamber and left atrium, and conducted
      mitral annuloplasty and maze procedure. Arrhythmia were not encountered after
      surgery. The maze procedure and resection of the anomalous septum with mitral
      surgery proved to be effective for atrial fibrillation with cor triatriatum. 

PMID- 26197832
TI  - [Lung Abscess Diagnosed as Adenocarcinoma by Needle Biopsy;Report of a Case].
AB  - We report a case of lung abscess misdiagnosed as adenocarcinoma based on
      cytologic findings of the sample obtained from needle biopsy. A 45-year-old man
      consulted our hospital because of fever, wet cough and an abnormal shadow on a
      chest X-ray film. A chest computed tomography revealed gradually enlarging
      pulmonary mass in the left S6 infiltrating the S5. A diagnosis of lung cancer was
      suspected and surgery was performed. Pathological findings of the specimen showed
      atypical cells with a large nucleus and a gross papillary neoplasm by needle
      biopsy. The patient underwent left lower lobectomy and partial resection of upper
      lobe with standard nodal dissection. The final diagnosis was a lung abscess with
      pneumonia without evidence of malignancy. When an indeterminate pulmonary tumor
      must be diagnosed during an operation, we should perform partial resection if
      possible. 

PMID- 26197831
TI  - [Massive Pulmonary Hemorrhage During Cardiac Operation;Report of a Case].
AB  - The incidence of pulmonary hemorrhage during cardiac operation is not freqent but
      one of severe and lethal complications. We report a case of massive pulmonary
      hemorrhage, hemoptysis, suspected to be induced by a Swan-Ganz catheter. The
      patient had satisfactory progress postoperatively. An 80-year-old female patient
      underwent mitral valve replacement, tricuspid annuloplasty, and maze procedure. A
      Swan-Ganz catheter was inserted via the right jugular vein and fixed just at 40
      cm as in usual preoperative induction. Operative procedures were uneventful, but
      active and massive airway hemorrhage started while weaning off cardiopulmonary
      bypass. A hematoma spreading under the visceral pleura of the right middle-lobe
      lung was found. We immediately replaced the endotracheal tube with a double-lumen
      one, and promptly decided to do lung lobectomy. These strategies were very
      helpful to rescue the patient, and led to her good recovery after the severe
      pulmonary hemorrhage, possibly induced by a catheter.

PMID- 26197833
TI  - [Pulmonary Carcinoid Tumor with Cushing's Syndrome in a Patient who Underwent
      Pulmonary Resection by Video-Assisted Thoracic Surgery;Report of a Case].
AB  - Pulmonary carcinoid tumor with Cushing's syndrome is comparatively rare disease.
      It is difficult to make an early diagnosis due to small size lesion in its early
      stage. We report a case of pulmonary carcinoid tumor with Cushing's syndrome
      successfully localised by positron emission tomography/computed tomography and
      was resected in the early stage. The levels of serum cortisol and
      adrenocorticotropic hormone( ACTH) decreased immediately after surgery, and the
      symptoms of Cushing's syndrome were relieved. 

PMID- 26197834
TI  - [Perforation of the Mediastinal Mature Teratoma;Report of a Case].
AB  - The mediastinal mature teratoma is uncommon in adult and sometimes ruptures. We
      present a case of perforation of mediastinal mature teratoma. A 22-year-old man,
      who had been scheduled for surgery to resect anterior mediastinal teratoma, was
      referred to our hospital due to sudden chest pain. The enhanced computed
      tomography findings suggested a perforation of the teratoma and the emergency
      surgery was performed. Extirpation of the tumor with partial resection of right
      upper lung, pericardium, and superior vena cava was performed. The histological
      diagnosis was mature teratoma and the defect of the mediastinal pleura was found
      to be the site of perforation. The patient was well and discharged from the
      hospital without complications. 

PMID- 26197835
TI  - [Pneumothorax Secondary to Pulmonary Metastasis of Angiosarcoma of the
      Scalp;Report of a Case].
AB  - Angiosarcoma has been reported as a rare case, having high potential of
      hematogeneous lung metastasis and then developing to pneumothorax with ease. The
      patient was a 74-year-old man afflicted with a malignant hemangio endothelioma
      (MHE) of the scalp. His MHE of the scalp was resected and skin grafting was made,
      then, he was administered docetaxel hydrate intravenously as adjuvant setting.
      Three years after, he complainted left chest pain and dyspnea, so his chest Xp
      was checked up and showed left pneumothorax. Chest computed tomography revealed
      multiple thin walled cavities of right and left lung and bullae with slightly
      thick walled cavity at apex legion of the left lung. We resected bullae with
      tumor of the left apex legion under video assisted thoracic surgery. After
      operation, He was administerd ricombinant interleukin-2 intravenously in order to
      control lung metastasis of the scalp, but his condition deteriorated and 6 months
      after pneumothorax he died. The average survival time from the 1st pneumothorax
      episode was only 4.7 months. He kept a good activities of daily living without
      reccurrence of pneumothorax by operation, so we thought that the operaion for
      pneumothorax with MHE was one option for therapy. 

PMID- 26197836
TI  - [Mediastinal Hemangioma with Literature Review;Report of a Case].
AB  - A 58-year-old woman visited a local physician for evaluation of collagen disease
      and screening computed tomography (CT) showed a posterior mediastinal tumor.
      After referral to our hospital, CT and magnetic resonance imaging (MRI) showed a
      mass, approximately 2 cm in diameter, located on the right of the 1st thoracic
      vertebra. Since a neurogenic tumor was suspected, thoracoscopic excision was
      performed. Surgical findings revealed a tumor between the 1st and 2nd ribs in the
      close vicinity of the right brachiocephalic vein. We severed blood vessels
      flowing into the tumor and removed it. The tumor, 25 mm in maximal diameter, was
      diagnosed as hemangioma by histological examinations. The prevalence of a
      hemangioma is less than 0.5% of all mediastinal tumors. Since it lacks specific
      imaging findings, its preoperative diagnosis is quite difficult to establish.
      Although a hemangioma in the mediastinum is quite rare, it should be included in
      the differential diagnoses of mediastinal tumors. 

PMID- 26197837
TI  - Head Transplantation: Editorial Commentary.

PMID- 26197838
TI  - Trace Amounts of Copper in Drinking Water Aggravate Cerebral Ischemic Injury via
      Impairing Endothelial Progenitor Cells in Mice.

PMID- 26197839
TI  - Pharmacokinetics of intravenous sildenafil in children with palliated single
      ventricle heart defects: effect of elevated hepatic pressures.
AB  - Aims Sildenafil is frequently prescribed to children with single ventricle heart
      defects. These children have unique hepatic physiology with elevated hepatic
      pressures, which may alter drug pharmacokinetics. We sought to determine the
      impact of hepatic pressure on sildenafil pharmacokinetics in children with single
      ventricle heart defects. METHODS: A population pharmacokinetic model was
      developed using data from 20 single ventricle children receiving single-dose
      intravenous sildenafil during cardiac catheterisation. Non-linear mixed effect
      modelling was used for model development, and covariate effects were evaluated
      based on estimated precision and clinical significance. RESULTS: The analysis
      included a median (range) of 4 (2-5) pharmacokinetic samples per child. The final
      structural model was a two-compartment model for sildenafil with a one
      compartment model for des-methyl-sildenafil (active metabolite), with assumed
      100% sildenafil to des-methyl-sildenafil conversion. Sildenafil clearance was
      unaffected by hepatic pressure (clearance=0.62 L/hour/kg); however, clearance of
      des-methyl-sildenafil (1.94*(hepatic pressure/9)(-1.33) L/hour/kg) was predicted
      to decrease ~7-fold as hepatic pressure increased from 4 to 18 mmHg. Predicted
      drug exposure was increased by ~1.5-fold in subjects with hepatic pressures ?10
      versus <10 mmHg (median area under the curve=533 versus 792 ug*h/L). Discussion
      Elevated hepatic pressure delays clearance of the sildenafil metabolite - des
      methyl-sildenafil - and increases drug exposure. We speculate that this results
      from impaired biliary clearance. Hepatic pressure should be considered when
      prescribing sildenafil to children. These data demonstrate the importance of
      pharmacokinetic assessments in patients with unique cardiovascular physiology
      that may affect drug metabolism.

PMID- 26197840
TI  - Umbilical Hernia in Peritoneal Dialysis Patients: Surgical Treatment and Risk
      Factors.
AB  - No previous reports have focused on surgical treatments and risk factors of
      umbilical hernia alone in peritoneal dialysis (PD) patients. Herein, we evaluated
      the treatments and risk factors. A total of 411 PD patients were enrolled. Of the
      15 patients with umbilical hernia (3.6%), six underwent hernioplasty. There was
      no recurrence in five patients treated with tension-free hernioplasty. The mean
      PD vintage after onset of hernia in the hernioplasty group tended to be longer
      than that in the non-hernioplasty group. An incarcerated hernia occurred in one
      non-hernioplasty patient. Although the incidence was significantly higher among
      women (P = 0.02), female sex was not a risk factor for umbilical hernia (P =
      0.08). Our findings suggest that umbilical hernias should be repaired for
      continuing PD. Furthermore, there were no significant risk factors for umbilical
      hernia in PD patients. Future studies with larger sample groups are required to
      elucidate these risk factors. 

PMID- 26197841
TI  - Assessing children's interpretations of the Aboriginal Children's Health and Well
      Being Measure (ACHWM).
AB  - BACKGROUND: There are emerging opportunities to improve the health of Aboriginal
      children and youth. The Aboriginal Children's Health and Well-being Measure
      (ACHWM) was developed to enable Aboriginal communities to obtain group-level data
      from the perspectives of their children 8 to 18 years of age. The survey was
      developed in collaboration with children, based on the Medicine Wheel framework.
      The purpose of this study was to ensure that children and youth interpreted the
      ACHWM questions consistently and accurately and to establish the face validity of
      the survey. METHODS: Children and parents/caregivers from the Wikwemikong Unceded
      Indian Reserve (Canada) participated in a detailed interview process as they
      completed the ACHWM, in 2012. Each participant worked through their thought
      process verbally, to enable the interviewer to identify questions that were
      misinterpreted or inconsistently interpreted. Questions were revised based on
      feedback from the participants, and reviewed with new participants until a stable
      version was established. The resulting version was reviewed by health care
      providers and community members to further ensure cultural relevance and face
      validity within the community. RESULTS: A total of 18 interviews, with 9 children
      and 9 caregivers, were required to achieve a stable version of the survey. The
      children ranged in age from 8 to 18 years. Revisions were required for 19
      questions. Most of these revisions were minor linguistic changes. In addition, 6
      questions were deleted due to consistent problems and 4 questions were created to
      address gaps identified during the process. Community members confirmed the
      appropriateness of the measure for their community and communicated their pride
      in their youth's role in the development of this survey. CONCLUSIONS: The result
      was a 58-question version of the ACHWM that was consistently interpreted and
      culturally appropriate, and had face validity confirmed by experts from the
      community, children and their parents/caregivers. The ACHWM is ready to be
      assessed for relevance to other Aboriginal communities.

PMID- 26197842
TI  - Severe Ebola Virus Infection With Encephalopathy: Evidence for Direct Virus
      Involvement.

PMID- 26197845
TI  - Editorial Commentary: Rapid Blood Culture Identification: The Value of a
      Randomized Trial.

PMID- 26197847
TI  - Polymyxin B hemoperfusion in septic shock: just look at the evidence!

PMID- 26197846
TI  - Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture
      Identification and Susceptibility Testing.
AB  - BACKGROUND: The value of rapid, panel-based molecular diagnostics for positive
      blood culture bottles (BCBs) has not been rigorously assessed. We performed a
      prospective randomized controlled trial evaluating outcomes associated with rapid
      multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly
      from positive BCBs. METHODS: A total of 617 patients with positive BCBs underwent
      stratified randomization into 3 arms: standard BCB processing (control, n = 207),
      rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with
      templated comments and real-time audit and feedback of antimicrobial orders by an
      antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was
      antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de
      escalation or escalation, length of stay (LOS), mortality, and cost. RESULTS:
      Time from BCB Gram stain to microorganism identification was shorter in the
      intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to
      the control group, both intervention groups had decreased broad-spectrum
      piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P =
      .01) and increased narrow-spectrum beta-lactam (control 42 hours, rmPCR 71 hours,
      rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%,
      rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate
      antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de
      escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001;
      escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups
      did not differ in mortality, LOS, or cost. CONCLUSIONS: rmPCR reported with
      templated comments reduced treatment of contaminants and use of broad-spectrum
      antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de
      escalation. CLINICAL TRIALS REGISTRATION: NCT01898208.

PMID- 26197848
TI  - Clinical outcome following sepsis due to bacteraemia in patients using
      glitazones: a matched case control study.

PMID- 26197849
TI  - Cytokine-enhanced maturation and migration to the lymph nodes of a human dying
      melanoma cell-loaded dendritic cell vaccine.
AB  - Dendritic cells (DCs) are professional APCs used for the development of cancer
      vaccines because of their ability to activate adaptive immune responses.
      Previously, we designed the DC/Apo-Nec vaccine using human DCs loaded with dying
      melanoma cells that primed Ag-specific cytotoxic T cells. Here, we evaluate the
      effect of a standard pro-inflammatory cytokine cocktail (CC) and adjuvants on
      DC/Apo-Nec maturation and migration. CC addition to the vaccine coculture allowed
      efficient Ag uptake while attaining strong vaccine maturation with an
      immunostimulatory profile. The use of CC not only increased CCR7 expression and
      the vaccine chemokine responsiveness but also upregulated matrix
      metalloproteinase-9 secretion, which regulated its invasive migration in vitro.
      Neither IL-6 nor prostaglandin E2 had a negative effect on vaccine preparation.
      In fact, all CC components were necessary for complete vaccine maturation.
      Subcutaneously injected DC/Apo-Nec vaccine migrated rapidly to draining LNs in
      nude mice, accumulating regionally after 48 h. The migrating cells of the CC
      matured vaccine augmented in proportion and range of distribution, an effect that
      increased further with the topical administration of imiquimod cream. The
      migrating proportion of human DCs was detected in draining LNs for at least 9
      days after injection. The addition of CC during DC/Apo-Nec preparation enhanced
      vaccine performance by improving maturation and response to LN signals and by
      conferring a motile and invasive vaccine phenotype both in vitro and in vivo.
      More importantly, the vaccine could be combined with different adjuvants.
      Therefore, this DC-based vaccine design shows great potential value for clinical
      translation.

PMID- 26197850
TI  - A different interpretation of the efficacy of lung cancer screening in the PLCO
      trial.

PMID- 26197844
TI  - No perinatal HIV-1 transmission from women with effective antiretroviral therapy
      starting before conception.
AB  - BACKGROUND: The efficacy of preventing perinatal transmission (PT) of human
      immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and
      treatment duration. The objective of this study was to determine whether
      initiating highly active antiretroviral therapy (ART) before conception has the
      potential to eliminate PT. METHODS: A total of 8075 HIV-infected mother/infant
      pairs included from 2000 to 2011 in the national prospective multicenter French
      Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with
      determined HIV infection status, and did not breastfeed. PT was analyzed
      according to maternal VL at delivery and timing of ART initiation. RESULTS: The
      overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651
      infants born to women who were receiving ART before conception, continued ART
      throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95%
      confidence interval [CI], 0.1%). VL and timing of ART initiation were
      independently associated with PT in logistic regression. Regardless of VL, the PT
      rate increased from 0.2% (6 of 3505) for women starting ART before conception to
      0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting
      during the first, second, or third trimester (P < .001). Regardless of when ART
      was initiated, the PT rate was higher for women with VLs of 50-400 copies/mL near
      delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9
      8.2). CONCLUSIONS: Perinatal HIV-1 transmission is virtually zero in mothers who
      start ART before conception and maintain suppression of plasma VL.

PMID- 26197851
TI  - Endometria from Obese PCOS Women with Hyperinsulinemia Exhibit Altered
      Adiponectin Signaling.
AB  - Hyperandrogenemia, hyperinsulinemia, and obesity affect 60-70% of patients with
      Polycystic Ovarian Syndrome (PCOS), who exhibit an altered endometrial insulin
      signaling. The aim of the study was to evaluate whether hyperandrogenism,
      hyperinsulinism, and obesity present in PCOS patients impair the endometrial
      adiponectin signaling pathway. The ex vivo study was conducted on 27 samples from
      lean (n=9), obese (n=9), and obese-PCOS (n=9) patients. The in vitro assays were
      performed in immortalized human endometrial stromal cells stimulated with
      testosterone, insulin, or testosterone plus insulin. Serum steroid-hormones,
      adiponectin, glucose, and insulin; body mass index, free androgen index, ISI
      Composite, and HOMA were evaluated in the 3 groups. Ex vivo and in vitro gene
      expression and protein content of adiponectin, AdipoR1, AdipoR2, and APPL1 were
      determined. Adiponectin serum levels were decreased in obese-PCOS patients
      compared to lean (78%) and obese (54%) controls (p<0.05). AdipoR1 protein and
      gene expression were increased in obese group vs. obese-PCOS and lean groups (2
      fold, p<0.05). In turn, AdipoR2 protein and mRNA content was similar between the
      3 groups. APPL1 protein levels were reduced in endometria from both obese groups,
      compared to lean group (6-fold, p<0.05). Testosterone plus insulin stimulation of
      T-HESC and St-T1b leads to a reduction of adiponectin, AdipoR1, AdipoR2, and
      APPL1 protein content in both endometrial cell lines (p<0.05), whereas, in the
      presence of testosterone or insulin alone, protein levels were similar to basal.
      Therefore, endometrial adiponectin-signaling pathway is impaired in
      hyperandrogenemic and hyperinsulinemic obese-PCOS patients, corroborated in the
      in vitro model, which could affect endometrial function and potentially the
      implantation process. 

PMID- 26197852
TI  - The GnRH Antagonist Degarelix Directly Inhibits Benign Prostate Hyperplasia Cell
      Growth.
AB  - Gonadotropin-releasing hormone receptors (GnRHR) have been found in
      extrapituitary tissues, including the prostate, where they might exert a local
      effect on tissue growth. Degarelix is a GnRHR antagonist approved for use in
      patients with prostate cancer (PCa) who need androgen deprivation therapy. The
      slowing of prostate cell growth is a common goal shared by PCa and benign
      prostate hyperplasia (BPH) patients, and the effect of degarelix on BPH cells has
      not yet been investigated. We wanted to evaluate the direct effect of degarelix
      on human BPH primary cell growth. Gene expression studies performed with BPH
      (n=11), stage 0 (n=15), and PCa (n=65) human specimens demonstrated the presence
      of GNRHR1 and GNRHR2 and their respective endogenous peptide ligands. BPH
      isolated epithelial and stromal cells were either cultured alone or co-cultured
      (1:4 or 4:1 ratio of epithelial to stromal cells) and subsequently treated with
      increasing concentrations of degarelix. Degarelix treatment induced a decrease in
      cell viability and cell proliferation rates, which occurred in parallel to an
      increase in apoptosis. Both epithelial and stromal BPH cells are sensitive to
      degarelix treatment and, interestingly, degarelix is also effective when the
      cells were growing in a co-culture microenvironment. In contrast to degarelix,
      the GnRHR agonists, leuprolide and goserelin, exerted no effect on the viability
      of BPH epithelial or stromal cells. In conclusion, (i) prostate tissues express
      GNRHR and are a potential target for degarelix; and (ii) degarelix directly
      inhibits BPH cell growth through a decrease in cell proliferation and an increase
      in apoptosis. Supporting information for this article is available online at
      http://www.thieme-connect.de/products. 

PMID- 26197853
TI  - The Emerging Role of Cardiovascular Magnetic Resonance Imaging in the Evaluation
      of Metabolic Cardiomyopathies.
AB  - The aim of this review is to discuss the role of Cardiovascular Magnetic
      Resonance (CMR) in the diagnosis, risk stratification, and follow-up of metabolic
      cardiomyopathies. The classification of myocardial diseases, proposed by WHO/ISFC
      task force, distinguished specific cardiomyopathies, caused by metabolic
      disorders, into 4 types: 1) endocrine disorders, 2) storage or infiltration
      disorders (amyloidosis, hemochromatosis and familial storage disorders), 3)
      nutritional disorders (Kwashiorkor, beri-beri, obesity, and alcohol), and 4)
      diabetic heart. Thyroid disease, pheochromocytoma, and growth hormone excess or
      deficiency may contribute to usually reversible dilated cardiomyopathy. Glucogen
      storage diseases can be presented with myopathy, liver, and heart failure.
      Lysosomal storage diseases can provoke cardiac hypertrophy, mimicking
      hypertrophic cardiomyopathy and arrhythmias. Hereditary hemochromatosis, an
      inherited disorder of iron metabolism, leads to tissue iron overload in different
      organs, including the heart. Cardiac amyloidosis is the result of amyloid
      deposition in the heart, formed from breakdown of normal or abnormal proteins
      that leads to increased heart stiffness, restrictive cardiomyopathy, and heart
      failure. Finally, nutritional disturbances and metabolic diseases, such as
      Kwashiorkor, beri-beri, obesity, alcohol consumption, and diabetes mellitus may
      also lead to severe cardiac dysfunction. CMR, through its capability to reliably
      assess anatomy, function, inflammation, rest-stress myocardial perfusion,
      myocardial fibrosis, aortic distensibility, iron and/or fat deposition can serve
      as an excellent tool for early diagnosis of heart involvement, risk
      stratification, treatment evaluation, and long term follow-up of patients with
      metabolic cardiomyopathies. 

PMID- 26197854
TI  - Future Prospects for the Treatment of Graves' Hyperthyroidism and Eye Disease.
AB  - Although there are adequate therapies for Graves' hyperthyroidism, mild to
      moderate Graves' orbitopathy (GO) is usually treated symptomatically whereas
      definitive therapy is reserved for severe, vision-threatening GO. Importantly,
      none of the treatment regimens for Graves' disease used today are directed at the
      pathogenesis of the disease. Herein, we review some aspects of what is known
      about the pathogenesis of these 2 major components of Graves' disease,
      specifically the apparent important roles of the TSH and IGF-1 receptors, and
      thereafter describe future therapeutic approaches directed at these receptors. We
      propose that targeting these receptors will yield effective and better tolerated
      treatments for Graves' disease, especially for GO. 

PMID- 26197855
TI  - Outcome Prediction of Treatment of Graves' Hyperthyroidism with Antithyroid
      Drugs.
AB  - Graves' disease is the most common cause of hyperthyroidism in iodine-replete
      areas and is ultimately due to antibodies interacting with the TSH receptor on
      thyroid follicular cells [TSH-receptor antibody (TRAb)]. Antithyroid drugs (ATDs)
      belonging to the family of thionamides are the first-line treatment in Europe.
      ATD treatment is commonly continued for 18-24 months. Its major limitation is the
      high rate of relapses after drug withdrawal. Factors particularly bound to
      subsequent relapses are the large thyroid volume, smoking habit, persistence of
      TRAb in the circulation at the end of treatment, and the post-partum period.
      Under these conditions, consideration should be given to a definitive therapy for
      hyperthyroidism (radioiodine treatment, thyroidectomy), particularly if the
      patient is at risk of cardiovascular complications that might be exacerbated by
      persistence or recurrence of hyperthyroidism. 

PMID- 26197856
TI  - Platinum sensitivity and non-cross-resistance of cisplatin analogue with
      cisplatin in recurrent cervical cancer.
AB  - OBJECTIVE: The concept of platinum sensitivity and cross-resistance among
      platinum agents are widely known in the management of recurrent ovarian cancer.
      The aim of this study was to evaluate two hypotheses regarding the validity of
      the concept of platinum sensitivity and non-cross-resistance of cisplatin
      analogue with cisplatin in recurrent cervical cancer. METHODS: In this
      retrospective study, the clinical data of patients with recurrent cervical
      cancer, who had a history of receiving cisplatin based chemotherapy (including
      concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line
      chemotherapy at the time of recurrence between April 2004 and July 2012 were
      reviewed. RESULTS: In total, 49 patients--34 squamous cell carcinomas (69.4%) and
      15 non-squamous cell carcinomas (30.6%)--were enrolled. The median age was 53
      years (range, 26 to 79 years). Univariate and multivariate analysis showed that a
      platinum free interval (PFI) of 12 months has a strong relationship with the
      response rate to second-line chemotherapy. Upon multivariate analysis of survival
      after second-line platinum-based chemotherapy, a PFI of 12 months significantly
      influenced both progression-free survival (hazard ratio [HR], 0.349; 95%
      confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR,
      0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6
      months, the difference of progression-free survival between patients with re
      administration of cisplatin (3.0 months) and administration of cisplatin analogue
      (7.2 months) as second-line chemotherapy was statistically significant (p=0.049,
      log-rank test). CONCLUSION: The concept of platinum sensitivity could be applied
      to recurrent cervical cancer and there is a possibility of noncross-resistance of
      cisplatin analogue with cisplatin.

PMID- 26197857
TI  - Transvaginal/transrectal ultrasound for assessing myometrial invasion in
      endometrial cancer: a comparison of six different approaches.
AB  - OBJECTIVE: To compare the diagnostic performance of six different approaches for
      assessing myometrial infiltration using ultrasound in women with carcinoma of the
      corpus uteri. METHODS: Myometrial infiltration was assessed by two-dimensional
      (2D) transvaginal or transrectal ultrasound in 169 consecutive women with well
      (G1) or moderately (G2) differentiated endometrioid type endometrial carcinoma.
      In 74 of these women three-dimensional (3D) ultrasound was also performed. Six
      different techniques for myometrial infiltration assessment were evaluated. The
      impression of examiner and Karlsson's criteria were assessed prospectively.
      Endometrial thickness, tumor/uterine 3D volume ratio, tumor distance to
      myometrial serosa (TDS), and van Holsbeke's subjective model were assessed
      retrospectively. All subjects underwent surgical staging within 1 week after
      ultrasound evaluation. Definitive histopathological data regarding myometrial
      infiltration was used as gold standard. Sensitivity and specificity for all
      approaches were calculated and compared using McNemar test. RESULTS: The
      impression of examiner and subjective model performed similarly (sensitivity
      79.5% and 80.5%, respectively; specificity 89.6% and 90.3%, respectively). Both
      methods had significantly better sensitivity than Karlsson's criteria
      (sensitivity 31.8%, p<0.05) and endometrial thickness (sensitivity 47.7%,
      p<0.05), and better specificity than tumor/uterine volume ratio (specificity
      28.3%, p<0.05) and TDS (specificity 41.5%, p<0.05). CONCLUSION: Subjective
      impression seems to be the best approach for assessing myometrial infiltration in
      G1 or G2 endometrioid type endometrial cancer by transvaginal or transrectal
      ultrasound. The use of mathematical models and other objective 2D and 3D
      measurement techniques do not improve diagnostic performance.

PMID- 26197858
TI  - Robotic high para-aortic lymph node dissection with high port placement using
      same port for pelvic surgery in gynecologic cancer patients.
AB  - OBJECTIVE: This study reports our initial experience of robotic high para-aortic
      lymph node dissection (PALND) with high port placement using same port for pelvic
      surgery in cervical and endometrial cancer patients. METHODS: Between July 2013
      and January 2014, we performed robotic high PALND up to the left renal vein
      during staging surgeries. With high port placement and same port usage for pelvic
      surgery, high PALND was successfully performed without repositioning the robotic
      column. All data were registered consecutively and analyzed retrospectively.
      RESULTS: All patients successfully underwent robotic high PALND, followed by
      hysterectomy and pelvic lymph node dissection. Median age was 45 years (range, 39
      to 51 years) and median body mass index was 22 kg/m2 (range, 19.3 to 23.1 kg/m2).
      Median operative time for right PALND and left PALND was 37 minutes (range, 22 to
      65 minutes) and 44 minutes (range, 36 to 50 minutes), respectively. Median number
      of right and left para-aortic lymph node by pathologic report was 12 (range, 8 to
      15) and 13 (range, 5 to 26). CONCLUSION: With high port placement and one
      assistant port, robotic high PALND with the same port used in pelvic surgery is
      feasible to non-obese patients.

PMID- 26197859
TI  - Improving survival after endometrial cancer: the big picture.
AB  - To improve survival in women with endometrial cancer, we need to look at the "big
      picture" beyond initial treatment. Although the majority of women will be
      diagnosed with early stage disease and are cured with surgery alone, there is a
      subgroup of women with advanced and high-risk early stage disease whose life
      expectancy may be prolonged with the addition of chemotherapy.
      Immunohistochemistry will help to identify those women with Lynch syndrome who
      will benefit from more frequent colorectal cancer surveillance and genetic
      counseling. If they happen to be diagnosed with colorectal cancer, this
      information has an important therapeutic implication. And finally, because the
      majority of women will survive their diagnosis of endometrial cancer, they remain
      at risk for breast and colorectal cancer, so these women should be counselled
      about screening for these cancers. These three interventions will contribute to
      improving the overall survival of women with endometrial cancer. 

PMID- 26197861
TI  - Impact of statins on risk and survival of ovarian cancer.

PMID- 26197860
TI  - The Korean guideline for cervical cancer screening.
AB  - The incidence rate of cervical cancer in Korea is still higher than in other
      developed countries, notwithstanding the national mass-screening program.
      Furthermore, a new method has been introduced in cervical cancer screening.
      Therefore, the committee for cervical cancer screening in Korea updated the
      recommendation statement established in 2002. The new version of the guideline
      was developed by the committee using evidence-based methods. The committee
      reviewed the evidence for the benefits and harms of the Papanicolaou test, liquid
      based cytology, and human papillomavirus (HPV) testing, and reached conclusions
      after deliberation. The committee recommends screening for cervical cancer with
      cytology (Papanicolaou test or liquid-based cytology) every three years in women
      older than 20 years of age (recommendation A). The cervical cytology combined
      with HPV test is optionally recommended after taking into consideration
      individual risk or preference (recommendation C). The current evidence for
      primary HPV screening is insufficient to assess the benefits and harms of
      cervical cancer screening (recommendation I). Cervical cancer screening can be
      terminated at the age of 74 years if more than three consecutive negative
      cytology reports have been confirmed within 10 years (recommendation D). 

PMID- 26197862
TI  - Personal technical considerations about en bloc pelvic resection.

PMID- 26197863
TI  - Pathogenesis and diagnostic criteria for rickets and osteomalacia--proposal by an
      expert panel supported by the Ministry of Health, Labour and Welfare, Japan, the
      Japanese Society for Bone and Mineral Research, and the Japan Endocrine Society.
AB  - Rickets and osteomalacia are diseases characterized by impaired mineralization of
      bone matrix. Recent investigations have revealed that the causes of rickets and
      osteomalacia are quite variable. Although these diseases can severely impair the
      quality of life of affected patients, rickets and osteomalacia can be completely
      cured or at least respond to treatment when properly diagnosed and treated
      according to the specific causes. On the other hand, there are no standard
      criteria to diagnose rickets or osteomalacia nationally and internationally.
      Therefore, we summarize the definition and pathogenesis of rickets and
      osteomalacia, and propose diagnostic criteria and a flowchart for the
      differential diagnosis of various causes of these diseases. We hope that these
      criteria and the flowchart are clinically useful for the proper diagnosis and
      management of these diseases. 

PMID- 26197864
TI  - Scientific Misconduct in India: Causes and Perpetuation.
AB  - Along with economic strength, space technology and software expertise, India is
      also a leading nation in fraudulent scientific research. The problem is worsened
      by vested interests working in concert for their own benefits. These self
      promoting cartels, together with biased evaluation methods and weak penal
      systems, combine to perpetuate scientific misconduct. Some of these issues are
      discussed in this commentary, with supporting examples and possible solutions.

PMID- 26197865
TI  - High-Resolution, Large-Area Fabrication of Compliant Electrodes via Laser
      Ablation for Robust, Stretchable Dielectric Elastomer Actuators and Sensors.
AB  - A key element in stretchable actuators, sensors, and systems based on elastomer
      materials are compliant electrodes. While there exist many methodologies for
      fabricating electrodes on dielectric elastomers, very few succeed in achieving
      high-resolution patterning over large areas. We present a novel approach for the
      production of mechanically robust, high-resolution compliant electrodes for
      stretchable silicone elastomer actuators and sensors. Cast, 2-50 MUm thick
      poly(dimethylsiloxane) (PDMS)-carbon composite layers are patterned by laser
      ablation and subsequently bonded to a PDMS membrane by oxygen plasma activation.
      The technique affords great design flexibility and high resolution and readily
      scales to large-area arrays of devices. We validate our methodology by producing
      arrays of actuators and sensors on up to A4-size substrates, reporting on
      microscale dielectric elastomer actuators (DEA) generating area strains of over
      25%, and interdigitated capacitive touch sensors with high sensitivity yet
      insensitivity to substrate stretching. We demonstrate the ability to cofabricate
      highly integrated multifunctional transducers using the same process flow,
      showing the methodology's promise in realizing sophisticated and reliable complex
      stretchable devices with fine features over large areas. 

PMID- 26197866
TI  - Advanced oxidation protein products induce apoptosis in podocytes through
      induction of endoplasmic reticulum stress.
AB  - Although podocyte apoptosis has been shown to be induced by the accumulation of
      advanced oxidation protein products (AOPPs), the mechanisms through which AOPPs
      trigger apoptosis in these cells remain unclear. In this study, we investigated
      the role of endoplasmic reticulum (ER) stress in AOPP-induced podocyte apoptosis.
      AOPP treatment induced overexpression of glucose-regulated protein 78 and
      CCAAT/enhancer-binding protein-homologous protein (CHOP) in podocytes, indicating
      that AOPPs induced ER stress. Notably, AOPP-induced increase in the rate of
      podocyte apoptosis was partly reversed by salubrinal, an ER stress inhibitor,
      whereas the AOPP effect was reproduced by an inducer of ER stress, thapsigargin,
      suggesting that AOPPs triggered podocyte apoptosis by inducing ER stress.
      Furthermore, AOPP-induced reactive oxygen species (ROS) generation, ER stress,
      and podocyte apoptosis were significantly inhibited by an nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase inhibitor, a ROS scavenger, or receptor of
      advanced glycation end products (RAGE) small interfering RNA (siRNA). Moreover,
      silencing of the three ER stress sensors, protein kinase-like ER kinase (PERK),
      activating transcription factor 6 (ATF6), and inositol requiring 1 (IRE1),
      respectively, significantly lowered the apoptotic rate of the cells compared with
      that of the scramble siRNA-transfected cells. Lastly, our data suggested that
      CHOP- and caspase-12-dependent pathways were involved in ER stress-mediated
      podocyte apoptosis and that Bcl-2 suppression was involved in CHOP-mediated
      apoptosis. Collectively, our results indicate for the first time that AOPPs
      trigger podocyte apoptosis through induction of ER stress, which might be
      regulated by NADPH oxidase-dependent ROS through RAGE, and that this apoptosis is
      mediated by three unfolded protein response pathways, the PERK, ATF6, and IRE1
      pathways, and the mediators, CHOP and caspase-12. 

PMID- 26197867
TI  - Vegetarian Diets for Weight Loss: How Strong is the Evidence?

PMID- 26197868
TI  - Lung cancer: developments, concepts, and specific aspects of the new WHO
      classification.
AB  - INTRODUCTION: Diagnostic methods and algorithms for the diagnosis of pulmonary
      neoplasms have considerably changed over the recent years. Based on large-scale
      molecular characterization studies and the development of targeted therapies,
      precise morphological, immunohistochemical, and molecular pathological tumor
      subtyping is now of utmost importance for evidence-based treatment decisions.
      Changes of diagnostic concepts initially referred to biopsies and cytology
      specimens but are now also transferred to resection specimens. METHODS: This
      review is focused on recent developments in morphological and immunohistochemical
      subtyping of pulmonary neoplasms and concepts of tumor progression. It also
      provides perspectives on relevant changes of diagnostic concepts within the
      context of the new WHO classification. CONCLUSION: It becomes apparent that a
      three-step diagnostic concept based on morphology, immunohistochemistry, and
      molecular pathology is important to meet the requirements of an increasingly more
      complex, interdisciplinary care of lung cancer patients and to allow for
      reliable, clinically meaningful tumor diagnoses.

PMID- 26197869
TI  - How does biomass distribution change with size and differ among species? An
      analysis for 1200 plant species from five continents.
AB  - We compiled a global database for leaf, stem and root biomass representing c. 11
      000 records for c. 1200 herbaceous and woody species grown under either
      controlled or field conditions. We used this data set to analyse allometric
      relationships and fractional biomass distribution to leaves, stems and roots. We
      tested whether allometric scaling exponents are generally constant across plant
      sizes as predicted by metabolic scaling theory, or whether instead they change
      dynamically with plant size. We also quantified interspecific variation in
      biomass distribution among plant families and functional groups. Across all
      species combined, leaf vs stem and leaf vs root scaling exponents decreased from
      c. 1.00 for small plants to c. 0.60 for the largest trees considered. Evergreens
      had substantially higher leaf mass fractions (LMFs) than deciduous species,
      whereas graminoids maintained higher root mass fractions (RMFs) than
      eudicotyledonous herbs. These patterns do not support the hypothesis of fixed
      allometric exponents. Rather, continuous shifts in allometric exponents with
      plant size during ontogeny and evolution are the norm. Across seed plants,
      variation in biomass distribution among species is related more to function than
      phylogeny. We propose that the higher LMF of evergreens at least partly
      compensates for their relatively low leaf area : leaf mass ratio. 

PMID- 26197870
TI  - Finite-Element Modelling of the Response of the Gerbil Middle Ear to Sound.
AB  - We present a finite-element model of the gerbil middle ear that, using a set of
      baseline parameters based primarily on a priori estimates from the literature,
      generates responses that are comparable with responses we measured in vivo using
      multi-point vibrometry and with those measured by other groups. We investigated
      the similarity of numerous features (umbo, pars-flaccida and pars-tensa
      displacement magnitudes, the resonance frequency and break-up frequency, etc.) in
      the experimental responses with corresponding ones in the model responses, as
      opposed to simply computing frequency-by-frequency differences between
      experimental and model responses. The umbo response of the model is within the
      range of variability seen in the experimental data in terms of the low-frequency
      (i.e., well below the middle-ear resonance) magnitude and phase, the main
      resonance frequency and magnitude, and the roll-off slope and irregularities in
      the response above the resonance frequency, but is somewhat high for frequencies
      above the resonance frequency. At low frequencies, the ossicular axis of rotation
      of the model appears to correspond to the anatomical axis but the behaviour is
      more complex at high frequencies (i.e., above the pars-tensa break-up). The
      behaviour of the pars tensa in the model is similar to what is observed
      experimentally in terms of magnitudes, phases, the break-up frequency of the
      spatial vibration pattern, and the bandwidths of the high-frequency response
      features. A sensitivity analysis showed that the parameters that have the
      strongest effects on the model results are the Young's modulus, thickness and
      density of the pars tensa; the Young's modulus of the stapedial annular ligament;
      and the Young's modulus and density of the malleus. Displacements of the tympanic
      membrane and manubrium and the low-frequency displacement of the stapes did not
      show large changes when the material properties of the incus, stapes,
      incudomallear joint, incudostapedial joint, and posterior incudal ligament were
      changed by +/-10 % from their values in the baseline parameter set. 

PMID- 26197871
TI  - Temporal Resolution of the Normal Ear in Listeners with Unilateral Hearing
      Impairment.
AB  - Unilateral hearing loss (UHL) leads to an imbalanced input to the brain and
      results in cortical reorganization. In listeners with unilateral impairments,
      while the perceptual deficits associated with the impaired ear are well
      documented, less is known regarding the auditory processing in the unimpaired,
      clinically normal ear. It is commonly accepted that perceptual consequences are
      unlikely to occur in the normal ear for listeners with UHL. This study
      investigated whether the temporal resolution in the normal-hearing (NH) ear of
      listeners with long-standing UHL is similar to those in listeners with NH.
      Temporal resolution was assayed via measuring gap detection thresholds (GDTs) in
      within- and between-channel paradigms. GDTs were assessed in the normal ear of
      adults with long-standing, severe-to-profound UHL (N = 13) and age-matched, NH
      listeners (N = 22) at two presentation levels (30 and 55 dB sensation level).
      Analysis indicated that within-channel GDTs for listeners with UHL were not
      significantly different than those for the NH subject group, but the between
      channel GDTs for listeners with UHL were poorer (by greater than a factor of 2)
      than those for the listeners with NH. The hearing thresholds in the normal or
      impaired ears were not associated with the elevated between-channel GDTs for
      listeners with UHL. Contrary to the common assumption that auditory processing
      capabilities are preserved for the normal ear in listeners with UHL, the current
      study demonstrated that a long-standing unilateral hearing impairment may
      adversely affect auditory perception--temporal resolution--in the clinically
      normal ear. From a translational perspective, these findings imply that the
      temporal processing deficits in the unimpaired ear of listeners with unilateral
      hearing impairments may contribute to their overall auditory perceptual
      difficulties.

PMID- 26197872
TI  - Houttuynia cordata aqueous extract attenuated glycative and oxidative stress in
      heart and kidney of diabetic mice.
AB  - PURPOSE: The anti-glycative and anti-oxidative effects from Houttuynia cordata
      leaves aqueous extract (HCAE) in heart and kidney of diabetic mice were examined.
      METHODS: HCAE, at 1 or 2 %, was supplied in drinking water for 8 weeks. Plasma
      glucose and blood urea nitrogen (BUN) levels and creatine phosphokinase (CPK)
      activity were measured. The production of oxidative and inflammatory factors was
      determined. Activity and protein expression of associated enzymes or regulators
      were analyzed. RESULTS: HCAE intake at both doses lowered plasma glucose and BUN
      levels, and CPK activity and also restored creatinine clearance rate in diabetic
      mice. HCAE intake, only at 2 %, retained plasma insulin levels (P < 0.05). HCAE
      reduced reactive oxygen species, protein carbonyl, interleukin-6, tumor necrosis
      factor-alpha, N (epsilon) -(carboxymethyl)-lysine, pentosidine and fructose
      levels, and reserved glutathione content in heart and kidney of diabetic mice (P
      < 0.05). Diabetes enhanced aldose reductase (AR) activity and protein expression
      in heart and kidney (P < 0.05). HCAE intake at both doses decreased renal AR
      activity and protein expression, but only at 2 % lowered cardiac AR activity and
      protein expression (P < 0.05). Diabetes increased protein expression of RAGE,
      p47(phox) and gp91(phox), nuclear factor kappa-B (NF-kappaB) p50, NF-kappaB p65
      and mitogen-activated protein kinase in heart and kidney (P < 0.05). HCAE intake
      only at 2 % limited RAGE expression, but at 1 and 2 % downregulated p47(phox), NF
      kappaB p65 and p-p38 expression in these organs (P < 0.05). CONCLUSIONS: These
      findings suggest that Houttuynia cordata leaves aqueous extract could ameliorate
      cardiac and renal injury under diabetic condition.

PMID- 26197874
TI  - Reliability of a food menu to measure energy and macronutrient intake in
      adolescents.
AB  - BACKGROUND/OBJECTIVES: The aim of this study was to evaluate the reliability of a
      food menu to measure energy and macronutrient intake within the laboratory and
      under real-life conditions in adolescents. SUBJECTS/METHODS: A total of 12 boys
      and 8 girls (age 14.3 (s.d. 2.4) years, body mass index (BMI) 20.8 (s.d. 4.0)
      kg/m(2)) completed two identical in-laboratory sessions (ILS) and two out-of
      laboratory sessions (OLS). During the ILS, participants had ad libitum access to
      a variety of foods (74 items in total), which they chose from a menu every hour,
      for 5 h (0800-1300 h). For the OLS (1300 h until bedtime), the foods were chosen
      from the same menu at 1300 h and packed into containers to bring home with them.
      RESULTS: Test-retest analysis of energy and macronutrient intake revealed no
      significant differences (ILS and OLS). Intra-class correlations ranged between
      0.69 and 0.83 (ILS) and between 0.48 and 0.73 (OLS) for energy and macronutrient
      intake (all P<0.01). Within-subject coefficients of variation ranged between
      12.9% and 23.5% for the ILS and between 24.0% and 37.7% for the OLS. Bland-Altman
      plots showed acceptable agreement. Finally, the food menu was well appreciated by
      the participants with a 75% appreciation rate on a visual analog scale.
      CONCLUSIONS: This food menu provides a reasonably reliable measure of energy and
      macronutrient intake in adolescents, irrespective of sex and BMI, especially
      inside the laboratory setting. Despite the difficulties in capturing a stable
      measure of energy intake in research, this tool could be a useful addition to the
      methods currently used to assess ad libitum food intake in youth.

PMID- 26197873
TI  - The need for multisectoral food chain approaches to reduce trans fat consumption
      in India.
AB  - BACKGROUND: The World Health Organization (WHO) recommends virtually eliminating
      trans fat from the global food supply. Although several high-income countries
      have successfully reduced trans fat levels in foods, low- and middle-income
      countries such as India face additional challenges to its removal from the food
      supply. This study provides a systems analysis of the Indian food chain to assess
      intervention options for reducing trans fat intake in low-income consumers.
      METHODS: Data were collected at the manufacturer, retailer and consumer levels.
      Qualitative interviews were conducted with vanaspati manufacturers (n = 13) and
      local food vendors (n = 44). Laboratory analyses (n = 39) of street foods/snacks
      sold by the vendors were also conducted. Trans fat and snack intakes were also
      examined in low-income consumers in two rural villages (n = 260) and an urban
      slum (n = 261). RESULTS: Manufacturers of vanaspati described reducing trans fat
      levels as feasible but identified challenges in using healthier oils. The fat
      content of sampled oils from street vendors contained high levels of saturated
      fat (24.7-69.3 % of total fat) and trans fat (0.1-29.9 % of total fat).
      Households were consuming snacks high in trans fat as part of daily diets (31 %
      village and 84.3 % of slum households) and 4 % of rural and 13 % of urban
      households exceeded WHO recommendations for trans fat intakes. CONCLUSIONS: A
      multisectoral food chain approach to reducing trans fat is needed in India and
      likely in other low- and middle-income countries worldwide. This will require
      investment in development of competitively priced bakery shortenings and economic
      incentives for manufacturing foods using healthier oils. Increased production of
      healthier oils will also be required alongside these investments, which will
      become increasingly important as more and more countries begin investing in palm
      oil production.

PMID- 26197875
TI  - Dietary counselling and nutritional support in oropharyngeal cancer patients
      treated with radiotherapy: persistent weight loss during 1-year follow-ups.
AB  - BACKGROUND/OBJECTIVES: The need for dietary counselling and nutritional support
      in oropharyngeal cancer patients is generally accepted. However, evidence for the
      effectiveness is sparse. The aim of this study was to describe dietary
      counselling, nutritional support, body weight and toxicity during and after
      treatment, and investigate the effect of pre-treatment body mass index (BMI) on
      survival in oropharyngeal cancer patients. SUBJECTS/METHODS: A retrospective
      chart review was made in 276 oropharyngeal cancer patients treated with
      radiotherapy (RT). End points were dietary consultations, weight loss, toxicity,
      overall survival and disease-free survival. RESULTS: Almost all oropharyngeal
      cancer patients received dietary counselling (94%) and nutritional support (99%).
      Dietary counselling decreased sharply shortly after treatment to 38% at 1 year
      after treatment. Overall weight loss increased during the first year of follow-up
      and ranged from 3% at start of RT, until 11% at 1 year after RT. Overall survival
      was significantly longer for patients with a BMI above average (P=0.01). Acute
      dysphagia (P=0.001), mucositis (P=0.000) and toxicity grade 3 (P=0.002) were
      significantly more prevalent in patients who had lost 10% or more of their body
      weight. CONCLUSIONS: This study showed that patients continue to lose body weight
      during and until 1 year after treatment, despite nutrition support and frequent
      dietetic consultation. A BMI above average appears to increase survival time.
      Future studies, preferably randomized trials, are needed to compare standard
      dietary counselling with more intensive dietary counselling that consists of
      earlier and/or prolonged treatment.

PMID- 26197876
TI  - Deterioration of mental health in bariatric surgery after 10 years despite
      successful weight loss.
AB  - BACKGROUND/OBJECTIVE: The present study evaluated the mental health and
      psychological functioning of bariatric patients before surgery, and after 1 year
      and 10 year follow-ups, and compared them with participants in a dietary program.
      Such long follow-up is rare, but strongly recommended by the American Association
      of Bariatric Surgeons. SUBJECTS/METHODS: Thirty-six bariatric surgery patients
      and 34 participants of a weight loss program were weighed and assessed at all 3
      points in time. Participants were administered the mental health inventory,
      neuroticism, sense of control and fear of intimacy scales. Along with these
      mental and psychological measurements, the medical outcome short form (SF-36) was
      used. RESULTS: The surgery group achieved successful weight loss outcomes (27%
      reduction of pre-operative weight) after 10 years and better than baseline health
      related quality-of-life scores. However, their general mental health,
      neuroticism, sense of control and fear of intimacy scores showed significant
      deterioration in comparison to pre-operative levels after 10 years. The dietary
      group participants remained psychologically stable among all three points in
      time. CONCLUSIONS: This study highlights the importance of identifying a risk
      group among bariatric patients for which the dietary and psychological follow-up
      may be of special significance.

PMID- 26197877
TI  - Association of serum vitamin D with change in weight and total body fat in a
      German cohort of older adults.
AB  - We examined the association of baseline serum 25-hydroxyvitamin D (25(OH)D) with
      change in weight and total body fat in a cohort of community-dwelling older
      adults from Southern Germany. A total of 735 participants of the population-based
      KORA-Age Study (2009-2012), aged 65-90 years, were followed for 2.9+/-0.1 years.
      Body fat was assessed with bioelectrical impedance analysis. Linear and
      multinomial logistic models, adjusted for baseline covariables, were used to
      examine the association of 25(OH)D with percentage weight and body fat change
      during follow-up. 25(OH)D levels were not associated with overall weight change
      or body fat loss. Higher 25(OH)D levels were associated with a lower likelihood
      of having gained >3% of body fat in women but not in men. As we cannot exclude
      residual confounding by outdoor physical activity and diet, our results are not
      sufficient to support a causal role of 25(OH)D in the etiology of obesity in
      Caucasian older adults. 

PMID- 26197878
TI  - Suppression of miR-221 inhibits glioma cells proliferation and invasion via
      targeting SEMA3B.
AB  - BACKGROUND: Gliomas are the most common primary tumors in the central nervous
      system. Due to complicated signaling pathways involved in glioma progression,
      effective targets for treatment and biomarkers for prognosis prediction are still
      scant. RESULTS: In this study we revealed that a new microRNA (miR), the miR-221,
      was highly expressed in the glioma cells, and suppression of miR-221 resulted in
      decreased cellular proliferation, migration, and invasion in glioma cells.
      Mechanistic experiments validated that miR-221 participates in regulating glioma
      cells proliferation and invasion via suppression of a direct target gene, the
      Semaphorin 3B (SEMA3B). The rescue experiment with miR-221 and SEMA3B both
      knockdown results in significant reversion of miR-221 induced phenotypes.
      CONCLUSION: Taken together, our findings highlight an unappreciated role for miR
      221 and SEMA3B in glioma.

PMID- 26197879
TI  - A novel cis-AB variant allele arising from a de novo nucleotide substitution
      c.796A>G (p.M266V) in the B glycosyltransferase gene.
AB  - BACKGROUND: Cis-AB, a rare ABO variant, is the result of a mutated ABO gene that
      produces a glycosyltransferase enzyme with dual A and B glycosyltransferase
      activity. It may lead to ABO discrepancies and a delay in establishing the blood
      group. To date, there have been no reports of a de novo mutation leading to a cis
      AB allele. OBJECTIVES AND METHODS: Sequencing of the ABO gene using blood and
      hair follicle cells from the proposita were performed along with blood from her
      parents. To establish maternity and paternity, short tandem repeat (STR) analysis
      was also performed. The A and B enzyme activities of the novel enzyme were
      measured in an in vitro expression study. RESULTS: A novel cis-AB allele arising
      from nucleotide substitution c.796A>G (p.M266V) in the B glycosyltransferase gene
      were discovered in the blood and hair follicle cells from the proposita, which
      was absent from her parents. In all 15 autosomal STR loci analysed, the
      probability of maternity and paternity were 0.999999 and 0.999989, respectively.
      The novel enzyme created 33.1% and 60.2% of A and B antigen compared to wild type
      A and B glycosyltransferases. CONCLUSION: A novel mechanism leading to a cis-AB
      allele was discovered.

PMID- 26197880
TI  - Advancing implementation science through measure development and evaluation: a
      study protocol.
AB  - BACKGROUND: Significant gaps related to measurement issues are among the most
      critical barriers to advancing implementation science. Three issues motivated the
      study aims: (a) the lack of stakeholder involvement in defining pragmatic measure
      qualities; (b) the dearth of measures, particularly for implementation outcomes;
      and (c) unknown psychometric and pragmatic strength of existing measures. Aim 1:
      Establish a stakeholder-driven operationalization of pragmatic measures and
      develop reliable, valid rating criteria for assessing the construct. Aim 2:
      Develop reliable, valid, and pragmatic measures of three critical implementation
      outcomes, acceptability, appropriateness, and feasibility. Aim 3: Identify
      Consolidated Framework for Implementation Research and Implementation Outcome
      Framework-linked measures that demonstrate both psychometric and pragmatic
      strength. METHODS/DESIGN: For Aim 1, we will conduct (a) interviews with
      stakeholder panelists (N = 7) and complete a literature review to populate
      pragmatic measure construct criteria, (b) Q-sort activities (N = 20) to clarify
      the internal structure of the definition, (c) Delphi activities (N = 20) to
      achieve consensus on the dimension priorities, (d) test-retest and inter-rater
      reliability assessments of the emergent rating system, and (e) known-groups
      validity testing of the top three prioritized pragmatic criteria. For Aim 2, our
      systematic development process involves domain delineation, item generation,
      substantive validity assessment, structural validity assessment, reliability
      assessment, and predictive validity assessment. We will also assess discriminant
      validity, known-groups validity, structural invariance, sensitivity to change,
      and other pragmatic features. For Aim 3, we will refine our established evidence
      based assessment (EBA) criteria, extract the relevant data from the literature,
      rate each measure using the EBA criteria, and summarize the data. DISCUSSION: The
      study outputs of each aim are expected to have a positive impact as they will
      establish and guide a comprehensive measurement-focused research agenda for
      implementation science and provide empirically supported measures, tools, and
      methods for accomplishing this work.

PMID- 26197881
TI  - The use of a single-step regenerative approach for the treatment of a replanted
      mandibular central incisor with severe resorption.
AB  - AIM: To report the clinical and radiographic treatment outcome of an immature
      replanted mandibular incisor with severe inflammatory external root resorption
      following a single-step regenerative approach. SUMMARY: A 7-year-old female
      patient was referred 1 week following an extrusion injury to her mandibular
      central incisor (tooth 31). There was a history of a 6 months previous avulsion
      injury to the same tooth, which had been replanted after 20 min of extra-oral
      time. On clinical examination, all teeth were asymptomatic and there was an arch
      wire splint placed on the mandibular incisors. Radiographic examination revealed
      severe inflammatory external root resorption of tooth 31. A diagnosis of necrotic
      pulp and asymptomatic apical periodontitis was made. Under local anaesthesia and
      rubber dam isolation, an access cavity was prepared. The canal was irrigated
      using 6% NaOCl solution delivered through the EndoVac negative pressure
      irrigation system (Endo Vac, Axis/SybronEndo, Coppell, TX, USA). A 17% EDTA
      solution was used for 5 min followed by a final rinse of sterile water. The
      periapical tissues were probed using a K-file, and bleeding was induced. A blood
      clot was allowed to form filling the entire canal. A thick plug of MTA was placed
      in direct contact with the blood clot. The tooth was restored with composite
      resin. All procedures were performed in a single visit. The splint was removed 2
      weeks later. Recall examination after 24 months revealed healthy soft tissues
      with normal periodontal probing and mobility. The 24 months radiographic
      evaluation revealed healing of the severe inflammatory external root resorption
      and continuous root development/dentine wall thickening of the apical third. No
      signs of ankylosis or significant discoloration was present.

PMID- 26197882
TI  - Electromyographic analysis of lower limb muscles during the golf swing performed
      with three different clubs.
AB  - The aim of this study was to describe and compare the EMG patterns of select
      lower limb muscles throughout the golf swing, performed with three different
      clubs, in non-elite middle-aged players. Fourteen golfers performed eight swings
      each using, in random order, a pitching wedge, 7-iron and 4-iron. Surface
      electromyography (EMG) was recorded bilaterally from lower limb muscles: tibialis
      anterior, peroneus longus, gastrocnemius medialis, gastrocnemius lateralis,
      biceps femoris, semitendinosus, gluteus maximus, vastus medialis, rectus femoris
      and vastus lateralis. Three-dimensional high-speed video analysis was used to
      determine the golf swing phases. Results showed that, in average handicap
      golfers, the highest muscle activation levels occurred during the Forward Swing
      Phase, with the right semitendinosus and the right biceps femoris muscles
      producing the highest mean activation levels relative to maximal electromyography
      (70-76% and 68-73% EMG(MAX), respectively). Significant differences between the
      pitching wedge and the 4-iron club were found in the activation level of the left
      semitendinosus, right tibialis anterior, right peroneus longus, right vastus
      medialis, right rectus femuris and right gastrocnemius muscles. The lower limb
      muscles showed, in most cases and phases, higher mean values of activation on
      electromyography when golfers performed shots with a 4-iron club.

PMID- 26197883
TI  - Vagal afferent-dependent cholecystokinin modulation of visceral pain requires
      central amygdala NMDA-NR2B receptors in rats.
AB  - BACKGROUND: Cholecystokinin (CCK), a gut hormone that is released during feeding,
      exerts gastrointestinal effects in part through vagal pathway. It is reported to
      be a potential trigger for increased postprandial visceral sensitivity in healthy
      subjects and, especially in patients with irritable bowel syndrome. NR2B
      containing N-methyl-d-aspartate (NMDA) receptors in the central amygdala (CeA)
      participate in pain modulation. Systemically administered CCK activates the CeA
      innervating neurons. Here, we investigated whether CCK modulation of visceral
      sensitivity is mediated through CeA NMDA-NR2B receptors and whether this
      modulation involves vagal pathway. METHODS: We first examined the visceromotor
      response (VMR) to colorectal distention (CRD) following i.p. injection of CCK
      octapeptide (CCK-8) in a rat model. Next, the NR2B antagonist ifenprodil and the
      NR2A antagonist NVP-AAM077 were microinjected into the CeA before systemic CCK
      injection. NR2B phosphorylation was detected by Western blot. To down-regulate
      NR2B gene expression, NR2B-specific small interfering RNA (siRNA) was delivered
      into CeA neurons by electroporation. In addition, the effects of functional
      deafferentation by perivagal application of capsaicin and pretreatment with the
      CCK1 receptor antagonist devazepide were investigated. KEY RESULTS: CCK-8
      increased VMR to CRD in a dose-dependent manner. This effect was blunted by intra
      CeA administration of ifenprodil (but not NVP-AAM077) and was accompanied by
      phosphorylation of NR2B subunits in the CeA. CCK failed to increase VMR to CRD in
      NR2B siRNA-treated rats. Perivagal capsaicin application and pretreatment with
      devazepide prevented CCK-induced pronociception and CeA NR2B phosphorylation.
      CONCLUSIONS & INFERENCES: The pronociception induced by systemic CCK, which is
      vagal afferent-dependent, requires activation of CeA NMDA-NR2B receptors.

PMID- 26197884
TI  - KIR3DL1*0040102 - a novel three-domain KIR subtype isolated from donors of
      African descent.
AB  - KIR3DL1*0040102 allele differs from KIR3DL1*0040101 by a single-nucleotide change
      at position 12356 (intron 6). 

PMID- 26197885
TI  - Simulated learning environment (SLE) in audiology education: A systematic review.
AB  - OBJECTIVE: To systematically review the relevant peer-review literature
      investigating the outcome of simulated learning environment (SLE) training in
      audiology education. DESIGN: A systematic review research design. STUDY SAMPLE:
      Fifteen databases were searched with four studies meeting the inclusion criteria.
      RESULTS: Three of the four studies revealed positive findings for the use of an
      SLE (that is, the SLE group showed a higher post-training score compared to the
      traditional training group or a significantly higher post-training score than the
      non-training groups). One study revealed negative findings where the traditional
      training group showed a significantly higher post-training score than the SLE
      group. In addition, both the studies comparing post- and pre-training scores
      reported significantly higher post-training scores than the pre-training scores
      of the participants that underwent SLE training. CONCLUSIONS: Overall, this
      review supports the notions that SLE training is an effective learning tool and
      can be used for basic clinical training. This conclusion should be treated with
      caution, considering the limited numbers of studies published in this area and
      future research should be conducted to cope with the gaps highlighted in this
      review.

PMID- 26197886
TI  - Midwives in Global Health: Championing Maternal Health in a Time of Shifting
      Development Paradigms.

PMID- 26197887
TI  - Education and Imaging. Gastrointestinal: Severe colon obstruction in acute
      pancreatitis.

PMID- 26197888
TI  - Risk factors and in-hospital outcome of acute ST segment elevation myocardial
      infarction in young Bangladeshi adults.
AB  - BACKGROUND: South Asians have a higher overall incidence rate and younger age of
      onset for acute myocardial infarction (AMI) compared to Western populations.
      However, limited information is available on the association of preventable risk
      factors and outcomes of AMI among young individuals in Bangladesh. The aim of
      this study was to determine the risk factors and in-hospital outcome of AMI among
      young (age <=40 years) adults in Bangladesh. METHODS: We conducted a prospective
      observational study among consecutive 50 patients aged <=40 years and 50 patients
      aged >40 years with acute ST Segment Elevation Myocardial Infarction (STEMI) and
      followed-up in-hospital at the National Institute of Cardiovascular Diseases
      (NICVD). Clinical characteristics, biochemical findings, diet, echocardiography
      and in-hospital outcomes were compared between the two groups. Multivariate
      logistic regression was performed to assess the association between risk factors
      and in-hospital outcome in young patients adjusting for other confounding
      variables. RESULTS: The mean age of the young and older patient groups was 36.5
      +/- 4.6 years and 57.0 +/- 9.1 years respectively. Male sex (OR 3.4, 95 % CI 1.2 
      9.75), smoking (OR 2.4, 95 % CI 1.04 - 5,62), family history of MI (OR 2.4, 95 %
      CI 1.11 - 5,54), homocysteine (OR 1.2, 95 % CI 1.08 - 1.36), eating rice >=2
      times daily (OR 3.5, 95 % CI 1.15 - 10.6) and eating beef (OR 4.5, 95 % CI 1.83 -
      11.3) were significantly associated with the risk of AMI in the young group
      compared to older group. In multivariate analysis, older patients had
      significantly greater chance of developing heart failure (OR 7.5, 95 % CI 1.51 to
      37.31), re-infarction (OR 7.0, 95 % CI 1.08 - 45.72), arrhythmia (OR 15.3, 95 %
      CI 2.69 - 87.77) and cardiogenic shock (OR 69.0, 95 % CI 5.81 - 85.52) than the
      younger group. CONCLUSION: Younger AMI patients have a different risk profile and
      better in-hospital outcomes compared to the older patients. Control of
      preventable risk factors such as smoking, unhealthy diet, obesity and
      dyslipidemia should be reinforced at an early age in Bangladesh.

PMID- 26197889
TI  - Quantification of gait parameters in freely walking rodents.
AB  - BACKGROUND: Qualitative and quantitative measurements of motor performance are
      essential for characterizing perturbations of motor systems. Although several
      methods exist for analyzing specific motor tasks, few behavioral assays are
      readily available to researchers that provide a complete set of kinematic
      parameters in rodents. RESULTS: Here we present MouseWalker, an integrated
      hardware and software system that provides a comprehensive and quantitative
      description of kinematic features in freely walking rodents. Footprints are
      visualized with high spatial and temporal resolution by a non-invasive optical
      touch sensor coupled to high-speed imaging. A freely available and open-source
      software package tracks footprints and body features to generate a comprehensive
      description of many locomotion features, including static parameters such as
      footprint position and stance patterns and dynamic parameters, such as step and
      swing cycle duration, and inter-leg coordination. Using this method, we describe
      walking by wild-type mice including several previously undescribed parameters.
      For example, we demonstrate that footprint touchdown occurs instantaneously by
      the entire paw with no obvious rostral-caudal or lateral-medial bias.
      CONCLUSIONS: The readily available MouseWalker system and the large set of
      readouts it generates greatly increases the currently available toolkit for the
      analysis of wild type and aberrant locomotion in rodents.

PMID- 26197890
TI  - Collapsing focal segmental glomerulosclerosis following long-term treatment with
      oral ibandronate: case report and review of literature.
AB  - BACKGROUND: Renal toxicity has been reported with bisphosphonates such as
      pamidronate and zolidronate but not with ibandronate, in the treatment of breast
      cancer patients with bone metastasis. One of the patterns of bisphosphonate
      induced nephrotoxicity is focal segmental glomerulosclerosis (FSGS) or its
      morphological variant, collapsing focal segmental glomerulosclerosis (CFSGS).
      CASE PRESENTATION: We describe a breast cancer patient who developed heavy
      proteinuria (protein/creatinine ratio 9.1) and nephrotic syndrome following
      treatment with oral ibandronate for 29 months. CFSGS was proven by biopsy. There
      was no improvement 1 month after ibandronate was discontinued. Prednisone and
      tacrolimus were started and she experienced a decreased in proteinuria.
      CONCLUSION: In patient who develops ibandronate-associated CFSGS, proteinuria
      appears to be at least partially reversible with the treatment of prednisone
      and/or tacrolimus if the syndrome is recognized early and ibandronate is stopped.

PMID- 26197891
TI  - Effects of miRNA-145 on airway smooth muscle cells function.
AB  - The pathological changes of airway smooth muscle (ASM) contribute to airway
      remodeling during asthma. Here, we investigated the effect of miR-145 on ASM
      function. We found that miR-145 was aberrantly more highly expressed in ASM cells
      exposed to cytokine stimulation that mimic the airway conditions of patients with
      asthma. Repression of miR-145 resulted in decreased ASM cell proliferation and
      migration in a dose-dependent manner and down-regulation of type I collagen and
      contractile protein MHC in ASM cells. qRT-PCR and Western blot analysis
      demonstrated that miR-145 negatively regulated the expression of downstream
      target Kruppel-like factor 4 (KLF4) protein, and overexpression of KLF4
      attenuated the effects of miR-145 on ASM cells. Further studies showed that KLF4
      significantly up-regulated the expression of p21 and down-regulated matrix
      metalloproteinase (MMP-2 and MMP-9). In conclusion, miR-145 overexpression in ASM
      cells significantly inhibited KLF4, and subsequently affected downstream p21, MMP
      2, and MMP-9 expressions, eventually leading to enhanced proliferation and
      migration of ASM cells in vitro. 

PMID- 26197892
TI  - Mitochondrial DNA sequence divergence and diversity of Glossina fuscipes fuscipes
      in the Lake Victoria basin of Uganda: implications for control.
AB  - BACKGROUND: Glossina fuscipes fuscipes is the main vector of African
      Trypanosomiasis affecting both humans and livestock in Uganda. The human disease
      (sleeping sickness) manifests itself in two forms: acute and chronic. The Lake
      Victoria basin in Uganda has the acute form and a history of tsetse re-emergence
      despite concerted efforts to control tsetse. The government of Uganda has
      targeted the basin for tsetse eradication. To provide empirical data for this
      initiative, we screened tsetse flies from the basin for genetic variation at the
      mitochondrial DNA cytochrome oxidase II (mtDNA COII) gene with the goal of
      investigating genetic diversity and gene flow among tsetse, tsetse demographic
      history; and compare these results with results from a previous study based on
      microsatellite loci data in the same area. METHODS: We collected 429 Gff tsetse
      fly samples from 14 localities in the entire Ugandan portion of the Lake Victoria
      coast, covering 40,000 km(2). We performed genetic analyses on them and added
      data collected for 56 Gff individuals from 4 additional sampling sites in the
      basin. The 529 pb partial mitochondrial DNA cytochrome oxidase II (mtDNA COII)
      sequences totaling 485 were analysed for genetic differentiation, structuring and
      demographic history. The results were compared with findings from a previous
      study based on microsatellite loci data from the basin. RESULTS: The differences
      within sampling sites explained a significant proportion of the genetic
      variation. We found three very closely related mtDNA population clusters, which
      co-occurred in multiple sites. Although Phi ST (0 - 0.592; P < 0.05) and Bayesian
      analyses suggest some level of weak genetic differentiation, there is no
      correlation between genetic divergence and geographic distance (r = 0.109, P =
      0.185), and demographic tests provide evidence of locality-based demographic
      history. CONCLUSION: The mtDNA data analysed here complement inferences made in a
      previous study based on microsatellite data. Given the differences in mutation
      rates, mtDNA afforded a look further back in time than microsatellites and
      revealed that Gff populations were more connected in the past. Microsatellite
      data revealed more genetic structuring than mtDNA. The differences in
      connectedness and structuring over time could be related to vector control
      efforts. Tsetse re-emergence after control interventions may be due to re
      invasions from outside the treated areas, which emphasizes the need for an
      integrated area-wide tsetse eradication strategy for sustainable removal of the
      tsetse and trypanosomiasis problem from this area.

PMID- 26197894
TI  - [Emergency Surgical Treatment of Stanford Type A Acute Aortic Dissection].
AB  - Our emergency surgical strategy for patients with Stanford type A acute aortic
      dissection is as follows. 1) Emergency surgery is conducted for patients with
      communicating aortic dissection. In addition, Emergency surgery is mandatory for
      patients within 24 hours after the onset of non-communicating aortic dissection.
      2) Ascending aorta replacement (including hemi-arch replacement) is performed in
      case of the intimal tear site is in the ascending aorta or in the descending
      aorta and the site is not identified. Total arch replacement is performed in case
      of the site is in the aortic arch. 3) Early organ reperfusion is preceded to the
      central repair operation for patients with complicated malperfusion. 4) After
      dissecting sufficiently the adventitial site of aortic root, transect the aortic
      dissection wall at 5 mm above the sinotubular junction so as not to leave false
      lumen cavity as much as possible. Our efforts adding revision to the surgical
      strategy and technique have improved the outcome of the treatment for Stanford
      type A acute aortic dissection.

PMID- 26197895
TI  - [Surgical and Endovascular Management for Acute Aortic Dissection Stanford Type
      B].
AB  - The most important decision for the patient's prognosis is whether we choose
      medical treatment or surgical therapy for the management of acute aortic
      dissection Stanford type B. Recent studies have reported outstanding initial
      success with entry closure by thoracic endovascular aortic repair( TEVAR) in the
      patients with Stanford type B aortic dissection. For acute aortic dissection
      Stanford type B with fatal complications, TEVAR is becoming the first-line
      therapy. Moreover, the efficacy of endovascular repair for the uncomplicated
      acute type B aortic dissection, in comparison with standard medical therapy, has
      been confirmed in some trials. In this report, we demonstrate a trend regarding
      surgical and endovascular treatment in addition to guidelines for the diagnosis
      and treatment of aortic aneurysm and aortic dissection (The Japanese Circulation
      Society 2011).

PMID- 26197896
TI  - [Ruptured Non-dissecting Thoracic Aortic Aneurysm].
AB  - Although the operative results for non-dissecting thoracic aneurysm has been
      improving markedly, that of the ruptured one is still poor. Once aneurysmal
      rupture is occurred, a patient can almost never survive. Only few patients could
      arrive to an emergency hospital. It is reported that about 60% of the patients
      are died suddenly and the remaining 40% of the patients may undergo surgery or
      endovascular intervention. In the annual report in 2012 published by "Journal of
      General Thoracic and Cardiovascular Surgery", the mortality rates during
      postoperative 30 days of the non-ruptured and the ruptured nondissecting thoracic
      aneurysm are 2.71% and 19.0% respectively. Thoracic endovascular aortic repair
      (TEVAR) is predominant alternatives for the patients with poor hemodynamic
      condition by rupture of aortic aneurysm. The mortality rate after TEVAR for
      ruptured thoracic aneurysm is reported to be 10.87%, and is lower than that of
      the open surgery. It is essential for preventing the death by aneurysmal rupture
      that the open surgery or TEVAR for thoracic aortic aneurysm should be carried out
      electively.

PMID- 26197893
TI  - Aggregatibacter actinomycetemcomitans, a potent immunoregulator of the
      periodontal host defense system and alveolar bone homeostasis.
AB  - Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has
      long been associated with localized aggressive periodontitis. The mechanisms of
      its pathogenicity have been studied in humans and preclinical experimental
      models. Although different serotypes of A. actinomycetemcomitans have
      differential virulence factor expression, A. actinomycetemcomitans cytolethal
      distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most
      extensively studied in the context of modulating the host immune response.
      Following colonization and attachment in the oral cavity, A.
      actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate
      defense mechanisms and drive a pathophysiologic inflammatory response. This supra
      physiologic immune response state perturbs normal periodontal tissue
      remodeling/turnover and ultimately has catabolic effects on periodontal tissue
      homeostasis. In this review, we have divided the host response into two systems:
      non-hematopoietic and hematopoietic. Non-hematopoietic barriers include
      epithelium and fibroblasts that initiate the innate immune host response. The
      hematopoietic system contains lymphoid and myeloid-derived cell lineages that are
      responsible for expanding the immune response and driving the pathophysiologic
      inflammatory state in the local periodontal microenvironment. Effector systems
      and signaling transduction pathways activated and utilized in response to A.
      actinomycetemcomitans will be discussed to further delineate immune cell
      mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss
      the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and
      dissect the catabolic disruption of balanced osteoclast-osteoblast-mediated bone
      remodeling, which subsequently leads to net alveolar bone loss.

PMID- 26197897
TI  - [Traumatic Thoracic Aortic Injury].
AB  - Thoracic aortic injuries need emergency treatment, but have a high mortality
      rate. Prompt appropriate diagnosis is crucial to rescue the patient. Endovascular
      repair has been a useful approach for patients who suffer from hemodynamic
      instability due to massive bleeding and multiple traumatic injuries. However,
      open repair can be applied on patients who are inappropriate for thoracic
      endovascular aortic repair (TEVAR) or in hemodynamic stability. We present 3
      cases of blunt aortic injury, who treated by TEVAR in 2 cases and open repair in
      1 case. 

PMID- 26197898
TI  - [Early Surgery for Active Infective Endocarditis].
AB  - Indication of emergent or urgent surgery for patients with active infective
      endocarditis is considered taking into acount the control of heart failure,
      infection, and systemic embolism. In cases with cerebral complication, however,
      the timing of surgery should be decided considering the extent of cerebral damage
      and the risk of exacerbation. Asymptomatic and small stroke may not preclude the
      early surgical intervention, although more severe cerebral complication, such as
      intracranial hemorrhage, should require delay of surgery at least for 4 weeks.
      Prevention of reinfection by total removal of infected tissues and reconstruction
      of defected tissues is the principle of surgery. We prefer the tissue
      reconstruction using bovine pericardium and prosthetic valve. However, extensive
      tissue destruction by microorganisms could make it difficult to achieve complete
      resection. In such cases, we use local administration of antibiotics layered with
      fibrin glue aiming at sustained release of antibiotics. 

PMID- 26197899
TI  - [Anastomotic Pseudoaneurysm after Aortic Root Replacement].
AB  - Aortic root replacement has been an established standard procedure to treat
      annuloaortic ectasia (AAE) or aortic root aneurysm associated with significant
      aortic valvular disease. The long-term outcome after the surgery has also been
      favorably reported;however, an occurrence of anastomotic pseudoaneurysm remains a
      dreadful and serious complication. Detection of asymptomatic pseudoaneurysm used
      to be a challenge, because conventional computed tomography (CT) scan often fails
      to reveal a presence of pseudoaneurysm formation mainly due to remarkable
      artifact from prosthetic valve or motion effect. Recent advance in
      electrocardiogram (ECG)-gated 3-dimentional (3D)-CT has led to visualize even a
      small pseudoaneurysm and delineate an exact origin of a pseudoaneurysm. This
      powerful diagnostic modality enables us to precisely plan therapeutic strategy to
      accomplish efficacious surgical repair or interventional radiological treatment
      when possible. 

PMID- 26197900
TI  - [Left Ventricular Rupture following Mitral Valve Replacement].
AB  - Left ventricular rupture is a rare but lethal complication after mitral valve
      replacement (MVR). Between 1989 and 2014, of 850 patients who underwent MVR, 6
      developed left ventricular rupture in Saitama Medical Center, Jichi Medical
      University. Treasure type I rupture occurred in 5 patients and Miller type III in
      1. Four cases developed ventricular rupture right after declamping of the
      ascending aorta, and the remaining 2 after the transfer to the intensive care
      unit( ICU). Prompt surgical therapy was achieved for the instant closure of the
      muscular wall defect under the cardiopulmonary bypass and cardiac arrest,
      however, leading to the disappointing result of 66.7% of hospital death. It is
      the most important to relieving the stress of the posterior wall of the left
      ventricle during mitral surgery by using the modification techniques with the
      preservation of posterior mitral leaflet and avoiding pre and afterload of the
      left ventricle right after the MVR. 

PMID- 26197901
TI  - [Coronary Artery Bypass Surgery in Acute Coronary Syndrome].
AB  - Acute coronary syndrome (ACS) is a critical situation. Early reperfusion is
      important to improve not only infarction size but also survival expectation rate.
      Percutaneous coronary intervention is in the 1st line in emergency situation to
      achieve earl perfusion. In this situation, urgent coronary artery bypass grafting
      (CABG) in ACS is indicated in patient with coronary anatomy not amenable to
      percutaneous transluminal coronary angioplasty (PCI) who have ongoing or
      recurrent ischemia, cardiogenic shock, severe heart failure, or other high-risk
      feature. When the patient does not require urgent treatment, CABG would be
      indicated according to the guideline for the management of stable angina as CABG
      is superior to PCI in regarding long-term survival and free from re-intervention.
      Even in any situations, decision making in heart team is important, especially in
      case of complicated and difficult situations.

PMID- 26197902
TI  - [Treatment for the Postinfarction Ventricular Defect].
AB  - Postinfarction ventricular septal defect (PIVSD) is uncommon but serious disease
      which normally required emergent surgery. Due to the severe hemodynamic condition
      of this disease, operative results are still poor even after the exclusion method
      was introduced by David and Komeda in 1990. In fact, the annual report in 2012 of
      General Thoracic Cardiovascular Surgery reported that the hospital mortality of
      the acute PIVSD was 26.7%. Percutaneous closure of PIVSD using the Amplatzer
      PIVSD device may be a reasonably effective treatment for the extremely poor-risk
      patients. 

PMID- 26197903
TI  - [Ventricular Free Wall Rupture].
AB  - Ventricular free wall rupture is an infrequent complication after acute
      myocardial infarction. However, it carries a high mortality rate. More than
      moderate amount of pericardial effusion (>=10 mm) is associated with an increased
      risk of free wall rupture. Surgery is superior to conservative treatment.
      Recently sutureless techniques, avoiding cardiopulmonary bypass, demonstrated
      relatively good survival rates. 

PMID- 26197904
TI  - [Total Anomalous Pulmonary Venous Connection].
AB  - Total anomalous pulmonary venous connection (TAPVC) is one of the most typical
      congenital heart defects requiring emergent surgery soon after birth. Obstruction
      of the pulmonary venous drainage that can lead to profound cyanosis, respiratory
      failure and shock indicates emergent intervention. Prenatal diagnosis of TAPVC
      contributes to a smooth transition from delivery to surgery. However, prenatal
      ultrasound screening frequently fails to reveal isolated TAPVC. In neonates with
      isolated obstructive TAPVC, common pulmonary venous chamber-to-left atrial
      anastomosis is the intervention of choice except in patients with severe
      intraventricular hemorrhage, extremely low birth weight, or gestational age of 30
      weeks or less. In neonates with right isomerism and functional single ventricle
      but severely obstructive TAPVC, prognosis after neonatal surgery is extremely
      poor. Catheter intervention to delay open heart surgery may be preferred in such
      neonates. 

PMID- 26197905
TI  - [Transposition of Great Artery].
AB  - Transposition of the great artery is one of common congenital cardiac disease
      resulting cyanosis. Death occurs easily in untreated patients with transposition
      and intact ventricular septal defect (VSD) in infancy at a few days of age when
      posterior descending coronary artery (PDA) closed. Since there are 2 parallel
      circulations, flow from pulmonary to systemic circulation is necessary for
      systemic oxygenation, and Balloon atrial septostomy or prostaglandin infusion
      should be performed especially if patient do not have VSD. Although the advent of
      fetal echocardiography, it is difficult to diagnose the transposition of the
      great arteries (TGA) as abnormality of great vessels is relatively
      undistinguishable. The diagnosis of transposition is in itself an indication for
      surgery, and arterial switch procedure is performed in the case the left
      ventricle pressure remains more than 2/3 of systemic pressure. Preoperative
      diagnosis is important as associated anomalies and coronary artery branching
      patterns are important to decide the operative indication and timing of surgery.

PMID- 26197906
TI  - [Current Surgical Treatment for Patients with Hypoplastic Left Heart Syndrome,
      from the Viewpoint of Emergent Operation].
AB  - Hypoplastic left heart syndrome (HLHS) is one of the most challenging congenital
      heart defects which require surgical interventions during neonatal period. Since
      the 1st successful surgical repair was reported by Norwood et al. more than 30
      years ago, some modifications in surgical maneuver [e. g. introduction of right
      ventricule (RV)-pulmonary artery (PA) shunt] and improvement of perioperative
      management have brought better outcome for this patient cohort. Recent years our
      institute have changed the treatment strategy from primary Norwood operation
      during neonatal period to bilateral PA banding and subsequent Norwood operation
      during early infantile (we call it as "rapid 2 stage Norwood operation"). Indeed,
      the introduction of this new strategy has lead to earlier hemodynamic
      stabilization after Norwood operation. Although these operations are performed
      electively for most of HLHS patients, emergent operations are necessary if they
      have restrictive inter-atrial communication with sever pulmonary congestion, or
      if their patent ductus arteriosus (PDA) s tend to close in spite of
      prostagrandine infusion, or if pulmonary over circulation develops so rapidly.
      Recently more than half of HLHS patients are diagonosed in fetal. The advances in
      fetal diagnosis allow us to find the patients earlier and to assess the severity
      of the disease. Most of HLHS patients who required emergent operation just after
      their birth are diagnosed in fetal. However, their surgical outcome is
      unsatisfactory so far. Treatment for these HLHS patients has become the next
      challenge.

PMID- 26197907
TI  - [Acute Mitral Regurgitation in Infant].
AB  - The acute mitral regurgitation of the infants are believed to be very rare until
      recently. However, there have been increasing number of reports of acute massive
      mitral regurgitation attributable to rupture of the chordae tendaniae escecially
      in Japan. If undiagnosed or the optimal treatment including surgery is delayed,
      it may cause cardiogenic shock and death in infants. Thus pediatricians,
      pediatric cardiologists and pediatric caridiac surgeons should consider this
      diagnosis when previously healthy infant suddenly develop cardiorespiratory
      collapse. It is very important to diagnose early and if there is over moderate
      mitral regurgitation, the 1st choice will be the mitral valve repair if possible.
      Pediatric cardiac suregon should be skilled at the mitral valve repair and mitral
      valve replacement. There are several techniques which are different from the
      adult operation, so pediatric cardiac surgeon also has to be prepared for these
      techniques including supraannular mitral valve replacement. 

PMID- 26197908
TI  - [Vetricular Assist Device Therapy for Acure Cardiogenic Shock].
AB  - The optimal treatment for severe heart failure is heart transplantation. However,
      owing to the lack of donor hearts, mechanical circulatory support is sometimes
      necessary to maintain life until a donor heart is available for transplantation.
      In Japan, an implantable ventricular assist devices (VADs) were accepted by the
      social healthcare insurance in 2011. The mid-term results of implantable VADs are
      reported to be excellent. However, the use of implantable VADs as a bridge to
      transplantation is limited in patients with a hemodynamic condition of
      Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)
      profile 2 or better rating. Therefore, an extracorporeal VAD has been utilized
      for patients with acute deteriorated hemodynamic conditions who have not yet been
      registered in the heart transplantation network. Because the extracorporeal VAD
      has been associated with high incidences of postoperative life-threatening
      complications such as stroke, bleeding and infection, its role is now limited to
      bridge to candidacy or bridge to recovery. The device should be removed if heart
      function is adequately recovered or should be converted to an implantable VAD
      immediately after the patient's systemic condition has recovered and the patient
      is registered in the heart transplantation network.

PMID- 26197909
TI  - [Emergency Surgery and Treatments for Pneumothorax].
AB  - The primary care in terms of emergency for pneumothorax is chest drainage in
      almost cases. The following cases of pneumothorax and the complications need
      something of surgery and treatments. Pneumothorax with subcutaneous emphysema
      often needs small skin incisions around the drainage tube. Tension pneumothorax
      often needs urgent chest drainage. Pneumothorax with intractable air leakage
      often needs interventional treatments like endobroncheal occlusion (EBO) or
      thoracographic fibrin glue sealing method (TGF) as well as urgent thoracoscopic
      surgery. Pneumothorax with acute empyema also often needs urgent thoracoscopic
      surgery within 2 weeks if chest drainage or drug therapy are unsuccessful. It
      will probably become chronic empyema of thorax after then. Pneumothorax with
      bleeding needs urgent thoracoscopic surgery in case of continuous bleeding over
      200 ml/2 hours. In any cases of emergency for pneumothorax, respiratory
      physicians should collaborate with respiratory surgeons at the 1st stage because
      it is important to timely judge conversion of surgical treatments from medical
      treatments.

PMID- 26197910
TI  - [Diagnosis and Treatment of Hemothorax].
AB  - Most cases of hemothorax are related to blunt trauma, procedures, neoplasm such
      as schwanommas of von-Recklinghausen disease and soft-tissue tumors, and vascular
      ruptures. Spontaneous pneumothorax is also a caused of spontaneous hemothorax.
      Hemothorax may result in respiratory distress, respiratory failure, retained
      clot, fibrothorax, empyema and extended hospitalization. We should attempt to
      clear the chest cavity as early in the hospital course as the patient's
      physiology will allow. The management of hemothorax has been a complex problem
      since it was 1st described over 200 years ago. Traditionally, lrage hemothorax is
      treated primarily by closed thoracic drainage by inserting a large-caliber chest
      tube in stable patients. In hemodynamically unstable patients with more than
      1,000 ml of blood drainage from the initial thoracotomy or ongoing blood losses
      of more than 100 to 200 ml/h, an early surgical approach with ongoing
      resuscitation is needed. Video-assisted thoracoscopic surgery (VATS), minimally
      invasive surgery, grows and finds new applications for the patients with
      hemothorax as both diagnostic and therapeutic interventions recently. VATS is an
      accurate, safe, and reliable operative therapy in the 5-day post event window,
      but there is a decreasing success rate after this time period. 

PMID- 26197911
TI  - [Traumatic Lung Injury].
AB  - Pulmonary injuries requiring thoracotomy are uncommon. Most patients with lung
      injuries can be treated with a simple tube thoracostomy. Resectional procedures
      include non-anatomic lung resection, formal lobectomy and formal pneumonectomy.
      Non-anatomic lung resection is indicated for control of hemorrhage, control of
      air leaks and resection of destroyed lung tissues. Lobectomy and pneumonectomy
      are indicated for control of major air leaks, and control of life-threatening
      hemorrhage. The high mortality rates reported for pneumonectomy when performed
      after traumatic lung injury. Video-assisted thoracoscopic surgery (VATS) also has
      been demonstrated to be a reliable operative therapy for lung injury. Surgical
      treatment of traumatic pulmonary injuries requires knowledge of multiple
      approaches and operative interventions.

PMID- 26197912
TI  - [Tracheobronchial Injury].
AB  - Tracheobronchial injuries (TBIs) are uncommon but potentially life-threatening.
      TBIs are mainly classified in 2 category, traumatic and iatrogenic. Most common
      symptoms are dyspnea, subcutaneous emphysema and pneumomediastinum. Pneumothorax
      is often found in lower tracheal or bronchial injury. Fiberoptic bronchoscopy is
      most important examination for TBI to detect injured site and its depth.
      Iatrogenic TBIs are caused by tracheal intubation, tracheostomy and airway
      intervention. Injury of iatrogenic TBIs are commonly laceration of membranous
      part. Surgical repair was performed for treatment of iatrogenic TBI. However,
      recently there has been reported many successful cases of non-operative
      treatment. Conservative treatment is a considerable choice of treatment. Approach
      of surgical repair depends on site of tracheal laceration. For laceration of
      cervical or upper mediastinal trachea, cervical approach is chosen. Recently
      transcervical-transtracheal repair were reported. Right posterolateral
      thoracotomy is suitable for repair of carina or main bronchus. Most of TBI caused
      by blunt trauma occur around carina. Operative treatment is mandatory in many
      cases. However morbidity and mortality are considerably high in emergent
      operation for traumatic TBI. It is necessary to make an appropriate strategy for
      treatment in an experienced trauma center. 

PMID- 26197913
TI  - [Massive Hemoptysis; Clinical Approach and Surgical Treatment].
AB  - Massive hemoptysis is a life-threatening condition which is defined by the
      American College of Radiology as more than 300-400 ml expectorated hemoptysis in
      24 hours. The major causes of massive hemoptysis are benign diseases including
      tuberculosis, aspergillosis, and pulmonary abscess. Bronchoscopy is mandatory for
      the initial assessment of hemoptysis and several transbronchial interventions may
      be performed in some cases. In addition, arteriography is another important
      modality for hemoptysis especially for the patients with poor general condition
      that have contraindications for surgery. Because of the progression of
      interventional vascular approach such as bronchial artery embolization (BAE), the
      number of patients who require emergency lung resection is decreasing. However,
      surgical resection is still should be considered the main approach for the
      patients with massive hemoptysis. In emergency circumstances, the combination of
      BAE and surgery will improve the patients' mortality and morbidity. This is
      especially true for elderly patients with tuberculosis, aspergillosis, and
      pulmonary abscesses, where early surgical approaches are warranted.

PMID- 26197914
TI  - [Acute Mediastinitis].
AB  - Acute mediastinitis is an infectious disease of differentiated etiology,
      characterized by a rapid and severe course. Causes, diagnosis, and treatment of
      acute mediastinitis was described. Our experience of descending necrotizing
      mediastinitis were demonstrated with chest X-ray, computed tomography (CT), and
      operative findings. Recognition, prompt diagnosis, and early treatment of the
      disease were emphasized. 

PMID- 26197915
TI  - [Current Management of Congenital Diaphragmatic Hernia].
AB  - Three types of congenital diaphragmatic hernias( Bochdalek hernia, Morgagni
      hernia, and esophageal hiatus hernia) are described with case presentation. In
      the Bochdalek hernia, the most common type of congenital diaphragmatic hernia,
      abdominal contents pass into the thorac bia diaphragmatic defect, limiting the
      space available for the developing lungs. Resulting lung hypoplasia, many infants
      experience severe respiratory distress within minutes of birth and may require
      resuscitation and stabilization of cardio-pulmonary function prior to surgery.
      The Morgagni hernia is rare and often incidentally diagnosed on routine chest x
      ray in asymptomatic patients. Repair is still advisable due to risk of
      strangulated bowel and respiratory distress. Esophageal hiatal hernias usually
      produce symptoms of gastroesophageal reflux( GERD) and rarely result in
      incarceration of stomach or other organs. Surgical interventions for GERD, such
      as Nissen fundoplication, usually target neurologically impaired children in
      order to prevent aspiration pneumonia and improve quality of life. Laparoscopic
      surgery is beneficial for all types of diaphragmatic hernia, especially in older
      children, but careful consideration should be made based on individual patient
      background. 

PMID- 26197916
TI  - [Traumatic Injury of the Diaphragm].
AB  - Traumatic diaphragmatic injury (TDI) is relatively rare condition, and is
      associated with high rates of morbidity and mortality. TDI usually results from
      blunt trauma and penetrating trauma. The majority causes of blunt TDI are victims
      of motor vehicle accidents. The incidence rates of TDI is unknown because of it
      can be overlooked if it is unsuspected with non-specific radiological and
      clinical findings. The mortality rates associated with blunt and penetrating TDI
      are affected by the severity of concurrent organ injuries. The diagnoses of TDI
      are frequently missed in the post-traumatic assessment because of non-specific
      symptoms or physical findings. When the site of trauma is in the abdomen, there
      will be high rate of an intra-abdominal organ injury. Furthermore, when the site
      of trauma is in the chest, there will be the abdominal organ injury in
      50%.Surgical operation should be performed as soon as possible for concomitant
      injuries. Diaphragmatic repair can be performed using laparotomy, thoracotomy, or
      both approaches. Primary suture of the diaphragm can be performed in the majority
      of TDI patients. The outcome of post TDI depends on concurrent organ injury. In
      case of emergency, it is important to take an appropriate diagnosis and treatment
      for any concomitant injuries.

PMID- 26197917
TI  - [Chest Wall Injury].
AB  - The thoracic wall protects the heart, great vessels, lungs, trachea, and
      bronchus, which are organs important for maintaining respiration/circulation,
      against external forces. Therefore, injury of the thoracic wall may necessitate
      emergency treatment. Such injury primarily consists of rib and sternal fractures.
      In particular, fractures of 2 or more consecutive ribs with each rib being
      fractured at 2 or more sites and serial rib fracture with sternal fracture lead
      to reverse thoracic movement involving contraction on inhalation and expansion on
      expiration. Such thoracic injury is termed flail chest. Injury of the thoracic
      wall, such as flail chest, markedly influences the prognosis. Therefore, it is
      necessary to promptly evaluate the general condition, involving
      respiratory/circulatory kinetics, confirm the presence or absence of concomitant
      injury, such as bruises of the lungs/heart, and accurately select therapeutic
      strategies, including artificial respiration and surgical intervention. 

PMID- 26197918
TI  - [Management for Life-threatening Mediastinal Tumor].
AB  - Mediastinal tumor occasionally causes life-threatening symptoms by infection,
      enlargement, and invasion to intrathoracic organs requiring an emergent
      treatment, while routine chest computed tomography (CT) can increasingly lead to
      incidental diagnosis of an asymptomatic mediastinal tumor. Cystic teratoma is one
      of the mediastinal tumors with lethal symptoms by rupture into the intrathoracic
      organs and/or cavities. Emergent tumor resection should be recommended when
      clinical characters suggest the diagnosis. Mediastinal tumors can cause airway
      stenosis by direct invasion and/or compression. Urgent airway reconstruction
      either by bronchoscopic interventions including stent or by surgery depends on
      causative diseases. Anterior mediastinal tumors such as thymic tumors can cause
      superior vena cava (SVC) syndrome. SVC reconstruction using a grafting method
      followed by radical tumor resection is recommended when the thymic epithelial
      tumor can be resectable. SVC reconstruction can provide a good quality of life
      and subsequent adjuvant therapy to some patients with the tumor responding to
      chemo-radiation therapy, even when the tumor is unresectable. The treatment
      strategy for lethal mediastinal tumors should be planned by physicians,
      radiologists and anesthesiologists other than thoracic surgeons. 

PMID- 26197919
TI  - [Idiopathic and Iatrogenic Esophageal Rupture].
AB  - Esophageal rupture is a rare emergency disorder. The leakage of gastric contents
      and foods can cause severe mediastinitis and pyothorax, occasionally resulting in
      the development of systemic sepsis and shock within hours. Iatrogenic injury to
      the esophagus is the most frequent cause of esophageal rupture, followed by
      spontaneous rupture. A plain chest roentgenogram, esophagogram, and chest
      computed tomography (CT) are necessary for the diagnosis of esophageal rupture,
      and early diagnosis reduces the rate of complications and mortality. The
      principle treatment is surgery. Drainage of the contents causing contamination,
      debridement of the infected tissue, and reinforcement of the primary closure of
      the ruptured lesion are essential for successful management. Spontaneous
      esophageal rupture frequently occurs on the left side of the lower thoracic
      esophagus. Rupture of the overlying pleura sometimes leads to systemic sepsis and
      shock. Iatrogenic rupture is commonly caused by endoscopic therapy. Nonoperative
      management is often appropriate in patients with this type of rupture. 

PMID- 26197920
TI  - [Foreign Body in Esophagus].
AB  - An esophageal foreign body is the term for a foreign body in the esophagus. The 2
      age groups most prone to this condition are children age 9 and under (and
      especially toddlers age 4 and under) and elderly individuals age 70 and over. A
      foreign body often lodges where the esophagus is most constricted. In toddlers,
      the foreign body is often currency or coins or a toy. In adults, the body is
      often a piece of fish, dentures, a piece of meat, a pin or needle, or a drug in
      its blister pack packaging. In children, an esophageal foreign body is treated by
      fluoroscopically guided removal of the body with a balloon catheter or magnetic
      catheter or removal of the body via endoscopy or direct esophagoscopy under
      general anesthesia. In adults, the best choice for treating an esophageal foreign
      body is removing the body with an endoscope but there are instances where surgery
      is performed because the body is hard to remove endoscopically, a puncture has
      occurred, or empyema or mediastinitis has developed. This paper reviews the
      diagnosis and treatment of an esophageal foreign body. 

PMID- 26197921
TI  - [Congenital Esophageal Atresia].
AB  - In this report, we describe the esophageal atresia in terms of current surgical
      management on the basis of our experience and literatures. Traditionally, infants
      with esophageal atresia have presented shortly after birth because of an
      inability to pass an orogastric tube, respiratory distress, or an inability to
      tolerate feeding. And also, an isolated trachea-esophageal fistula (TEF) usually
      cases coughing, recurrent pneumonia, or choking during feedings. To ignore these
      symptoms is to risk a delayed diagnosis. The condition may be associated with
      other major congenital anomalies such as those seen in the vertebral, anal,
      cardiac, tracheo-esophageal, renal/radial (VACTER) association, or it may be an
      isolated defect. Therapeutic strategies for esophageal atresia are a prevention
      of pulmonary complication by TEF closing and an early establishment of enteral
      alimentation. We promptly repair healthy infants without performing a gastrostomy
      and delay repair in infants with high-risk factors such as associated severe
      cardiac anomaly and respiratory insufficiency. Esophageal atresia has been
      classically approached through a thoracotomy. The disadvantages of such a
      thoracotomy have been recognized for a long time, for example winged scapula,
      elevation of fixation of shoulder, asymmetry of the chest wall, rib fusion,
      scoliosis, and breast and pectoral muscle maldevelopment. To avoid such
      disadvantages, thoracoscopic repair was recently reported.

PMID- 26197923
TI  - Correction: Au(i)-catalyzed synthesis of 8-oxabicyclo[3.2.1]oct-2-enes and 9
      oxabicyclo[3.3.1]nona-2,6-dienes from enynol via oxonium/Prins-type cyclization.

PMID- 26197924
TI  - Effect of variation in ovine WFIKKN2 on growth traits appears to be gender
      dependent.
AB  - WFIKKN2 may play a role in the regulation of muscle growth and development, but
      to date there have been no reports on the effect of variation in WFIKKN2 on
      growth and carcass traits in livestock. In this study, the effect of variation in
      ovine WFIKKN2 was investigated in 800 New Zealand Romney lambs (395 male and 405
      female), with five previously described variants (A to E) being identified.
      Variation in ovine WFIKKN2 was not found to affect various growth traits in the
      female lambs, but the presence of variant B was associated (P < 0.05) with
      decreased birth weight, tailing weight, weaning weight and pre-weaning growth
      rate; and increased post-weaning growth rate in male lambs. In male lambs, the
      presence of variant B was associated (P < 0.05) with an increased shoulder yield
      and proportion shoulder yield. No associations with growth or carcass traits were
      detected for the presence (or absence) of the other variants. These results
      suggest that variation in ovine WFIKKN2 may have a differential effect on growth
      in male and female lambs, and hence that the gene may be expressed in, or act in,
      a gender-specific fashion. 

PMID- 26197925
TI  - Novel function of a putative MOC1 ortholog associated with spikelet number per
      spike in common wheat.
AB  - Axillary meristems play an important role in determining final plant architecture
      and floral structures. Tomato Ls, Arabidopsis LAS and rice MOC1 are orthologous
      genes regulating axillary meristem initiation and outgrowth. Their functions are
      generally conserved but the functional specificities are divergent among species.
      Obvious differences between rice panicles and wheat spikes suggest the divergent
      functions of MOC1 and its wheat ortholog. We show that TaMOC1 might be involved
      in wheat spikelet development. TaMOC1 is a typical nucleus localized protein with
      transcriptional activation abilities. The variable N-termini of TaMOC1 protein is
      necessary for transcriptional activation. TaMOC1 is highly expressed in ears with
      length of 2, 3 and 6 cm. Significant associations between the TaMOC1-7A haplotype
      and spikelet number per spike were observed in ten environments over 3 years and
      2 sites. TaMOC1-7A HapH, a favored haplotype acquired during wheat
      polyploidization, may make a positive contribution to spikelet number per spike.
      Based on evolutionary analysis, geographic distribution and frequency changes,
      TaMOC1-7A HapH might be associated with wheat domestication and Chinese wheat
      breeding history. The pyramiding favorable alleles of TaMOC1-7A HapH and
      TaSnRK2.10 (C, associated with higher TGW) can improve both spikelet number per
      spike and TGW simultaneously.

PMID- 26197926
TI  - Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a
      polymerization template for downstream ASC.
AB  - AIM2 recognizes foreign dsDNA and assembles into the inflammasome, a filamentous
      supramolecular signalling platform required to launch innate immune responses. We
      show here that the pyrin domain of AIM2 (AIM2(PYD)) drives both filament
      formation and dsDNA binding. In addition, the dsDNA-binding domain of AIM2 also
      oligomerizes and assists in filament formation. The ability to oligomerize is
      critical for binding dsDNA, and in turn permits the size of dsDNA to regulate the
      assembly of the AIM2 polymers. The AIM2(PYD) oligomers define the filamentous
      structure, and the helical symmetry of the AIM2(PYD) filament is consistent with
      the filament assembled by the PYD of the downstream adaptor ASC. Our results
      suggest that the role of AIM2(PYD) is not autoinhibitory, but generating a
      structural template by coupling ligand binding and oligomerization is a key
      signal transduction mechanism in the AIM2 inflammasome. 

PMID- 26197927
TI  - Pegylated Interferon Mono-Therapy of Chronic Hepatitis C in the Dialysis
      Population: Systematic Review and Meta-Analysis.
AB  - The medical literature on mono-therapy with pegylated interferon for chronic
      hepatitis C in dialysis patients is mostly based on small clinical studies and
      the efficacy and safety of such approach is still unclear. A systematic review of
      the literature with a meta-analysis of clinical studies was performed in order to
      evaluate the efficacy and safety of mono-therapy with pegylated interferon of
      chronic hepatitis C in patients on regular dialysis. The primary outcome was
      sustained viral response (as a measure of efficacy); the secondary outcome was
      drop-out rate (as a measure of tolerability). The random-effects model of Der
      Simonian and Laird was used, with heterogeneity and sensitivity analyses. Twenty
      four clinical studies (N = 744 unique patients) were retrieved; five (21%) being
      randomized controlled trials. The summary estimate for sustained viral response
      and drop-out rate was 0.40 (95% confidence interval [CI], 0.35; 0.46) and 0.14
      (95% CI, 0.09; 0.20), respectively. The most frequent side-effects requiring
      discontinuation of treatment were hematological (31/83 = 37%) and
      gastrointestinal (9/31 = 10.8%). Meta-regression analysis showed a detrimental
      role of ageing on the frequency of sustained virological response (P = 0.01);
      drop-out rate was greater in diabetics (P < 0.005). Important heterogeneity was
      seen with regard to drop-out rate only. In summary, pegylated interferon
      monotherapy of hepatitis C in dialysis patients resulted unsatisfactory in terms
      of efficacy and safety. Studies with novel direct-acting antiviral agents in
      combination with pegylated interferon and ribavirin for the treatment of
      hepatitis C virus in dialysis population are under way. 

PMID- 26197928
TI  - Experimental demonstration of a quantum router.
AB  - The router is a key element for a network. We describe a scheme to realize
      genuine quantum routing of single-photon pulses based on cascading of conditional
      quantum gates in a Mach-Zehnder interferometer and report a proof-of-principle
      experiment for its demonstration using linear optics quantum gates. The
      polarization of the control photon routes in a coherent way the path of the
      signal photon while preserving the qubit state of the signal photon represented
      by its polarization. We demonstrate quantum nature of this router by showing
      entanglement generated between the initially unentangled control and signal
      photons, and confirm that the qubit state of the signal photon is well preserved
      by the router through quantum process tomography. 

PMID- 26197929
TI  - Developmentally regulated effects of severe hemorrhage on cardiovascular
      homeostasis and the arterial baroreflex control of heart rate.
AB  - The purpose of this study was to investigate in developing animals, the
      cardiovascular responses to severe hemorrhage at which compensatory mechanisms
      fail and when blood pressure remains decreased after blood loss. Two groups of
      conscious lambs (Group I: one to two weeks, N = 7; group II: six to seven weeks,
      N = 7) were studied. Mean arterial pressure, systolic and diastolic pressures,
      and heart rate were measured for 20 min before (Control, C) and for 60 min after
      a fixed hemorrhage of 30% of blood volume. The arterial baroreflex control of
      heart rate was assessed before (C), and at 30 and 60 min intervals after
      hemorrhage. Mean arterial pressure decreased for up to 60 min after hemorrhage in
      both groups of lambs. In group I, heart rate decreased from 200 +/- 29 (C) to 164
      +/- 24 beat min(-1) at 30 min then increased to 232 +/- 45 beat min(-1) at 60
      min, whereas heart rate remained unaltered in group II. With respect to the
      arterial baroreflex control of heart rate, by 30 min after hemorrhage in group I,
      there was a decrease in the heart rate range over which the baroreflex operates
      (P1) from 192 +/- 13 (C) to 102 +/- 9 beats min(-1); by 60 min after hemorrhage,
      there was a decrease in minimum heart rate (P4) from 72 +/- 10 (C) to 32 +/- 25
      beats min(-1). In group II, P1 decreased to a lesser extent than group I from 134
      +/- 21 (C) to 82 +/- 10 beats min(-1) at 30 min; minimum heart rate (P4)
      decreased from 40 +/- 15 (C) to 24 +/- 9 and 20 +/- 13 beats min(-1) at 30 and 60
      min, respectively. These results provide the first assessment of the arterial
      baroreflex control of heart rate following blood loss and new evidence that the
      cardiovascular responses to severe hemorrhage are developmentally regulated. 

PMID- 26197930
TI  - Food intake, tumor growth, and weight loss in EP2 receptor subtype knockout mice
      bearing PGE2-producing tumors.
AB  - Previous studies in our laboratory have demonstrated that prostaglandin (PG) E2
      is involved in anorexia/cachexia development in MCG 101 tumor-bearing mice. In
      the present study, we investigate the role of PGE receptor subtype EP2 in the
      development of anorexia after MCG 101 implantation in wild-type (EP2 (+/+)) or
      EP2-receptor knockout (EP2(-/-)) mice. Our results showed that host absence of
      EP2 receptors attenuated tumor growth and development of anorexia in tumor
      bearing EP2 knockout mice compared to tumor-bearing wild-type animals. Microarray
      profiling of the hypothalamus revealed a relative twofold change in expression of
      around 35 genes including mRNA transcripts coding for Phospholipase A2 and
      Prostaglandin D2 synthase (Ptgds) in EP2 receptor knockout mice compared to wild
      type mice. Prostaglandin D2 synthase levels were increased significantly in EP2
      receptor knockouts, suggesting that improved food intake may depend on altered
      balance of prostaglandin production in hypothalamus since PGE2 and PGD2 display
      opposing effects in feeding control. 

PMID- 26197931
TI  - The anorexic hormone Peptide YY3-36 is rapidly metabolized to inactive Peptide
      YY3-34 in vivo.
AB  - Peptide YY (PYY) is a 36 amino acid peptide hormone released from enteroendocrine
      cells. An N-terminally degraded metabolite, PYY3-36, has anorexigenic effects,
      which makes the PYY system a target for obesity treatment. However, little is
      known about the kinetics and degradation products of PYY. A related peptide,
      Neuropeptide Y (NPY), may be degraded from the C-terminus. We therefore
      investigated PYY degradation after in vitro incubations in porcine plasma and
      blood and in vivo by infusing PYY3-36 into multicatheterized pigs (n = 7) (2
      pmol/kg/min). Plasma samples were analyzed by region-specific radioimmunoassays
      (RIA) and HPLC analysis. A metabolite, corresponding to PYY3-34 was formed after
      incubation in plasma and blood and during the infusion study. When taking the C
      terminal degradation into account, the half-life (T1/2) of PYY in blood and
      plasma amounted to 3.4 +/- 0.2 and 6.2 +/- 0.2 h, respectively. After PYY3-36
      infusion in pigs, the peptide was degraded with a T1/2 of 3.6 +/- 0.5 min.
      Significant extraction (20.5 +/- 8.0%) compatible with glomerular filtration was
      observed across the kidneys and significant C-terminal degradation (26.5 +/-
      4.8%) was observed across the liver. Net balances across the hind limb,
      splanchnic bed, and lungs were not significantly different from zero. PYY3-34 was
      unable to activate the Y2 receptor in a transfected cell line. In conclusion,
      PYY3-36 is extensively degraded to PYY3-34 in the pig, a degradation that renders
      the peptide inactive on the Y2 receptor. Currently used assays are unlikely to be
      able to detect this degradation and therefore measure falsely elevated levels of
      PYY3-36, leading to underestimation of its physiological effects. 

PMID- 26197933
TI  - Divergent role of nitric oxide in insulin-stimulated aortic vasorelaxation
      between low- and high-intrinsic aerobic capacity rats.
AB  - Low-intrinsic aerobic capacity is associated with increased risk for
      cardiovascular and metabolic diseases and is a strong predictor of early
      mortality. The effects of intrinsic aerobic capacity on the vascular response to
      insulin are largely unknown. We tested the hypothesis that rats selectively bred
      for a low capacity to run (LCR) exhibit vascular dysfunction and impaired
      vascular reactivity to insulin compared to high capacity running (HCR) rats.
      Mature female LCR (n = 21) and HCR (n = 17) rats were maintained under sedentary
      conditions, and in vitro thoracic aortic vascular function was assessed. LCR
      exhibited greater body mass (13%), body fat (35%), and subcutaneous, perigonadal,
      and retroperitoneal adipose tissue mass, than HCR. During an intraperitoneal
      glucose tolerance test, glucose area under the curve (AUC) was not different but
      insulin AUC was 2-fold greater in LCR than HCR. Acetylcholine and insulin
      stimulated aortic vasorelaxation was significantly greater in LCR (65.2 +/- 3.8%,
      and 32.7 +/- 4.1%) than HCR (55.0 +/- 3.3%, and 16.7 +/- 2.8%). Inhibition of
      nitric oxide synthase (NOS) with L-NAME entirely abolished insulin-mediated
      vasorelaxation in the aorta of LCR, with no effect in HCR. LCR rats exhibited
      greater expression of Insulin Receptor protein, lower Endothelin Receptor-A
      protein, a down-regulation of transcripts for markers of immune cell infiltration
      (CD11C, CD4, and F4/80) and up-regulation of pro-atherogenic inflammatory genes
      (VCAM-1 and MCP-1) in the aorta wall. Contrary to our hypothesis, low-aerobic
      capacity was associated with enhanced aortic endothelial function and NO-mediated
      reactivity to insulin, despite increased adiposity and evidence of whole body
      insulin resistance. 

PMID- 26197932
TI  - Overload-induced skeletal muscle hypertrophy is not impaired in STZ-diabetic
      rats.
AB  - The aim of this study was to evaluate the effect of overload-induced hypertrophy
      on extensor digitorum longus (EDL) and soleus muscles of streptozotocin-induced
      diabetic rats. The overload-induced hypertrophy and absolute tetanic and twitch
      forces increases in EDL and soleus muscles were not different between diabetic
      and control rats. Phospho-Akt and rpS6 contents were increased in EDL muscle
      after 7 days of overload and returned to the pre-overload values after 30 days.
      In the soleus muscle, the contents of total and phospho-Akt and total rpS6 were
      increased in both groups after 7 days. The contents of total Akt in controls and
      total rpS6 and phospho-Akt in the diabetic rats remained increased after 30 days.
      mRNA expression after 7 days of overload in the EDL muscle of control and
      diabetic animals showed an increase in MGF and follistatin and a decrease in
      myostatin and Axin2. The expression of FAK was increased and of MuRF-1 and
      atrogin-1 decreased only in the control group, whereas Ankrd2 expression was
      enhanced only in diabetic rats. In the soleus muscle caused similar changes in
      both groups: increase in FAK and MGF and decrease in Wnt7a, MuRF-1, atrogin-1,
      and myostatin. Differences between groups were observed only in the increased
      expression of follistatin in diabetic animals and decreased Ankrd2 expression in
      the control group. So, insulin deficiency does not impair the overload-induced
      hypertrophic response in soleus and EDL muscles. However, different mechanisms
      seem to be involved in the comparable hypertrophic responses of skeletal muscle
      in control and diabetic animals. 

PMID- 26197934
TI  - Nanosecond Pulse Electric Field Activated-Platelet Rich Plasma Enhances the
      Return of Blood Flow to Large and Ischemic Wounds in a Rabbit Model.
AB  - Platelet-rich plasma is a therapeutic strategy used for accelerating wound
      healing of a wide range of tissues through the release of platelet growth
      factors. Here, we describe a nonchemical, safe method for preparing platelet-rich
      plasma using nanosecond-pulsed electric fields (nsPEFs) and investigated the
      effect of this platelet-rich plasma on reperfusion of blood in large skin flap or
      ischemic hind limb wounds in New Zealand White rabbits. Laser Doppler images of
      blood flow to the dorsal surface of skin flap wounds or to ischemic hind limb
      wounds were obtained from wounds treated with 0.9% saline or nanosecond-pulsed
      electric field prepared platelet-rich plasma (nsPRP). Reperfusion in the skin
      flap wounds was greater in the nsPRP-treated wounds than in the wounds treated
      with saline on postoperative days 3 (P < 0.001) and 21 (P < 0.03). Reperfusion in
      the ischemic hind-limb treated with nsPRP was greater than in the saline-treated
      limb on post-operative Day 3 (P < 0.001), post-operative week 1 (P < 0.025) and
      post-operative week 4 (P < 0.015). In the hind limb ischemic tissue, the number
      of endothelial cells, collagen, and cells containing vascular endothelial growth
      factor (VEGF) was greater in the nsPRP-treated tissue. These results demonstrate
      that nsPRP improves blood flow in large surgical skin wounds and in ischemic
      wounds. 

PMID- 26197935
TI  - Intramuscular anabolic signaling and endocrine response following high volume and
      high intensity resistance exercise protocols in trained men.
AB  - Resistance exercise paradigms are often divided into high volume (HV) or high
      intensity (HI) protocols, however, it is unknown whether these protocols
      differentially stimulate mTORC1 signaling. The purpose of this study was to
      examine mTORC1 signaling in conjunction with circulating hormone concentrations
      following a typical HV and HI lower-body resistance exercise protocol. Ten
      resistance-trained men (24.7 +/- 3.4 years; 90.1 +/- 11.3 kg; 176.0 +/- 4.9 cm)
      performed each resistance exercise protocol in a random, counterbalanced order.
      Blood samples were obtained at baseline (BL), immediately (IP), 30 min (30P), 1 h
      (1H), 2 h (2H), and 5 h (5H) postexercise. Fine needle muscle biopsies were
      completed at BL, 1H, and 5H. Electromyography of the vastus lateralis was also
      recorded during each protocol. HV and HI produced a similar magnitude of muscle
      activation across sets. Myoglobin and lactate dehydrogenase concentrations were
      significantly greater following HI compared to HV (P = 0.01-0.02), whereas the
      lactate response was significantly higher following HV compared to HI (P =
      0.003). The growth hormone, cortisol, and insulin responses were significantly
      greater following HV compared to HI (P = 0.0001-0.04). No significant differences
      between protocols were observed for the IGF-1 or testosterone response.
      Intramuscular anabolic signaling analysis revealed a significantly greater (P =
      0.03) phosphorylation of IGF-1 receptor at 1H following HV compared to HI.
      Phosphorylation status of all other signaling proteins including mTOR, p70S6k,
      and RPS6 were not significantly different between trials. Despite significant
      differences in markers of muscle damage and the endocrine response following HV
      and HI, both protocols appeared to elicit similar mTORC1 activation in resistance
      trained men. 

PMID- 26197936
TI  - Increased intrinsic mitochondrial respiratory capacity in skeletal muscle from
      rats with streptozotocin-induced hyperglycemia.
AB  - Type I diabetes mellitus (T1DM) is a chronic disorder, characterized by an almost
      or complete insulin deficiency. Widespread tissue dysfunction and deleterious
      diabetes-complications are associated with long-term elevations of blood glucose.
      The aim of this study was to investigate the effects of type I diabetes, as
      induced by streptozotocin, on the mitochondria in skeletal muscles that
      predominantly consist of either slow or fast twitch fibers. Soleus (primarily
      slow twitch fiber type) and the plantaris muscle (mainly fast twitch fiber type)
      were removed in order to measure mitochondrial protein expression and integrated
      mitochondrial respiratory function. Mitochondrial capacity for oxidative
      phosphorylation (OXPHOS) was found to be higher in the slow (more oxidative)
      soleus muscle from STZ rats when evaluating lipid and complex I linked OXPHOS
      capacity, whereas no difference was detected between the groups when evaluating
      the more physiological complex I and II linked OXPHOS capacity. These findings
      indicate that chronic hyperglycemia results in an elevated intrinsic
      mitochondrial respiratory capacity in both soleus and, at varying degree,
      plantaris muscle, findings that are consistent with human T1DM patients. 

PMID- 26197938
TI  - Knee arthroscopy: the science of art.

PMID- 26197937
TI  - Prognostic factors influencing the outcome of rotator cuff repair: a systematic
      review.
AB  - PURPOSE: To identify prognostic factors significantly associated with rotator
      cuff repair outcome and define the strength of these associations. METHODS:
      Search was performed using electronic databases. Studies reporting prognostic
      factors affecting rotator cuff repair outcome were included. Primary outcomes
      were: structural integrity, Disabilities of the Arm, Shoulder and Hand score,
      American Shoulder and Elbow Surgeons score, and Constant score. Each other
      outcome was considered as secondary outcome. Descriptive statistics was used.
      When possible, meta-analyses were performed. Methodological quality was assessed
      using the Quality In Prognosis Studies Tool. A best evidence synthesis was
      performed using the Grading of Recommendations Assessment, Development and
      Evaluation framework adapted to prognostic studies. RESULTS: Sixty-four studies
      were included. Methodological quality was high only for twelve studies. The
      overall quality of evidence was low to very low. Meta-analyses were possible only
      for seven studies. Older age and larger tears size were found to affect retear
      risk. Results were controversial for fatty infiltration, acromioclavicular joint
      or biceps procedures, acromiohumeral distance, delamination of tendon edges,
      musculotendinous junction position, number of tendons involved, and tendon
      length, quality and retraction. Baseline scores and workers compensation claim
      predicted functional outcomes. Subjective outcome was also affected by patient's
      expectations. CONCLUSIONS: Despite the large number of outcomes and prognostic
      factors evaluated by a relative small number of studies, almost not prognostic in
      design, it was not possible to reach any definitive conclusion regarding the most
      relevant predictors of outcome of rotator cuff repair. Moreover, the low
      methodological quality of the included studies and, subsequently, the low quality
      of evidence, seriously affected the strength of recommendation of the present
      review. Based on data available, retear risk is mainly affected by older age and
      larger tears size. Baseline scores and work compensation claim are the most
      significant predictors for functional outcomes. LEVEL OF EVIDENCE: Systematic
      review of level I-IV prognostic studies, Level IV.

PMID- 26197939
TI  - A comparison of three adjustable cortical button ACL fixation devices.
AB  - PURPOSE: Adjustable cortical fixation has gained popularity recently for ACL
      reconstruction; however, one concern with these types of devices is the potential
      for laxity occurring post-operatively. An indicator of clinical laxity is cyclic
      displacement during bench-top mechanical testing. The hypothesis was that the
      cyclic displacement and maximum strength of different adjustable buttons
      currently on the market would vary depending on their mechanism of fixation.
      METHODS: Three devices were studied: Biomet's ToggleLoc with ZipLoop Technology
      (ZL), Arthrex's TightRope RT (TR), and DePuy Mitek's RIGIDLOOP Adjustable (RLA).
      Each was tested in isolation on a servohydraulic test machine. The implants were
      pre-conditioned from 5 to 67 N for 10 cycles and then tested from 50 to 250 N for
      1000 cycles at 1 Hz. Following cyclic loading, a load to failure test was
      conducted at a rate of 20 mm/min. Total displacement was calculated from the 1st
      to the 1000th cycle, and ultimate strength and failure mode were recorded.
      RESULTS: Results showed that the RLA had significantly lower displacement versus
      both the TR (p = 0.012) and the ZL (p < 0.001). The TR also showed significantly
      lower displacement than the ZL (p < 0.001). The RLA and the ZL were both
      significantly stronger than the TR (p < 0.001). CONCLUSIONS: Both the RLA and TR
      showed clinically acceptable amounts of cyclic displacement and maximum strength.
      The clinical relevance of this study is that cyclic displacement results from
      bench-top tests may correlate with post-operative laxity, which ideally should be
      kept to a minimum.

PMID- 26197940
TI  - Effect of short-term oral immunotherapy with Cry j1-galactomannan conjugate on
      quality of life in Japanese cedar pollinosis patients: A prospective, randomized,
      open-label study.
AB  - OBJECTIVE: We have recently reported that a new regimen of short-term oral
      immunotherapy (OIT) with the Cry j1-galactomannan conjugate for Japanese cedar
      pollinosis (JCP) is effective to the improvement in the symptoms and medication
      use during the pollen season and relatively safe. The effect of OIT on quality of
      life (QOL) of JCP patients has not been assessed. Therefore, we evaluated for the
      first time the effect of OIT on QOL during the Japanese cedar/cypress pollen
      season. METHODS: A prospective, randomized, open-label trial was conducted over a
      period of 4 months. Participants were randomly divided into two groups. The OIT
      and control groups comprised 23 and 24 subjects, respectively. The build-up phase
      was initiated 1 month before the expected pollen season. The maintenance phase
      was continued for 51 days during the peak of the cedar pollen season. The QOL
      score in the Japan Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ) No.
      1 and visual analog scale (VAS) throughout the pollen season were evaluated.
      RESULTS: Participants receiving OIT showed significant improvements in the total
      QOL score and VAS throughout the pollen season compared with the control group.
      In addition, the mean total QOL score and VAS correlated in both groups during
      the pollen season. CONCLUSION: The new regimen of short-term OIT using the Cry j1
      galactomannan conjugate results in meaningful improvements in QOL of JCP
      patients. Our findings suggest that short-term OIT using allergen-galactomannan
      conjugates, as well as sublingual and subcutaneous immunotherapy, improves QOL of
      patients with pollinosis. The study was registered in UMIN-CTR (UMIN000013408) as
      the name of "a prospective, randomized, open study of oral Cry j1-galactomannan
      conjugate immunotherapy for Japanese cedar pollen allergy".

PMID- 26197941
TI  - Do physical qualities influence the attainment of professional status within
      elite 16-19 year old rugby league players?
AB  - OBJECTIVES: The current study retrospectively compared the physical qualities of
      elite academy rugby league players (aged 16-19 years) by career attainment level
      (i.e., academy or professional). DESIGN: Retrospective cross-sectional and
      longitudinal design. METHODS: Eighty-one academy rugby league players were
      assessed for physical qualities (height, body mass, skinfolds, speed, momentum,
      vertical jump, Yo-Yo Level 1 and 1-RM squat, bench press and prone row) at the
      Under 17-19 age categories between 2007 and 2012. Player's career attainment
      level was determined in 2014. Longitudinal changes in physical qualities between
      Under 17 and 19s were compared by career attainment level. RESULTS: Professional
      players demonstrated moderate significant advantages for height (d=0.98) and 1-RM
      squat (d=0.66) at the Under 17s, 1-RM bench press (d=0.76) at the Under 18s and 1
      RM prone row (d=0.73) at the Under 19s age categories when compared to academy
      players. When assessed longitudinally (Under 17s-19s), professional players
      significantly outperformed academy players for 1-RM squat (eta(2)=0.20).
      Professional players also demonstrated greater increases in body mass (8.2 vs.
      2.9kg) and 10m momentum (47 vs. 17kgs(-1)) than academy players between the Under
      17s and 19s. CONCLUSIONS: Advanced physical qualities, particularly height and
      absolute strength, within 16-19 year old players may contribute to attaining
      professional status in rugby league. Further, the development of body mass and
      momentum for players within an academy is an important consideration in the
      progress towards professional rugby league. Therefore, practitioners should aim
      to identify and develop the physical qualities, especially size and strength,
      within academy rugby league players.

PMID- 26197942
TI  - Physical self-confidence levels of adolescents: Scale reliability and validity.
AB  - OBJECTIVES: To establish reliability, content validity and concurrent validity of
      the physical self-confidence scale among adolescents. Demonstrate the use of this
      scale to assess the physical self-confidence of adolescents across genders at
      performing specific fundamental movement skills (FMS). DESIGN: Three hundred and
      seventy six adolescents were involved in this study. A 15 item scale was
      developed to assess physical self-confidence. METHODS: The scale was developed
      based on 15 specific FMS. Experts in the field reviewed the scale to ensure
      content validity. The reliability of the scale was assessed on a sub-sample of 67
      participants who answered the scale 7-days apart. Concurrent validity was
      assessed on the sub-sample using the Physical Self-Perception Profile (PSPP) as a
      comparative tool. 376 adolescents completed the physical self-confidence scale
      (mean age=13.78, SD=+/-1.21, males n=193) to assess gender differences, and also
      their levels of physical self-confidence across all skills. RESULTS: An Intra
      Class Correlation indicated excellent test retest reliability for the scale with
      an overall r=0.92. Content validity and concurrent validity were also good, with
      the scale achieving a correlation coefficient of 0.72 with the PSPP. Males
      possess significantly higher physical self-confidence than females across all
      items. CONCLUSIONS: This scale is the first reliable and valid tool which
      specifically measures physical self-confidence in performing FMS among
      adolescents. The results highlight gender differences in physical self-confidence
      and emphasise the importance of measuring this at skill level as differences were
      task specific. This scale will facilitate future research examining the
      relationship between self-confidence, FMS proficiency and physical activity
      participation.

PMID- 26197943
TI  - Systematic review of physical activity and cognitive development in early
      childhood.
AB  - OBJECTIVES: To comprehensively review all observational and experimental studies
      examining the relationship between physical activity and cognitive development
      during early childhood (birth to 5 years). DESIGN: Systematic review. METHODS:
      Electronic databases were searched in July, 2014. No study design, date, or
      language limits were imposed on the search. Included studies had to be published,
      peer reviewed articles that satisfied the a priori determined population
      (apparently healthy children aged birth to 5 years), intervention (duration,
      intensity, frequency, or patterns of physical activity), comparator (various
      durations, intensity, or patterns of physical activity), and outcome (cognitive
      development) study criteria. Study quality and risk of bias were assessed in
      December 2014. RESULTS: A total of seven studies, representing 414 participants
      from five different countries met the inclusion criteria, including two
      observational and five experimental studies. Six studies found increased or
      higher duration/frequency of physical activity had statistically significant
      (p<0.05) beneficial effects on at least one cognitive development outcome,
      including 67% of the outcomes assessed in the executive function domain and 60%
      in the language domain. No study found that increased or higher
      duration/frequency of physical activity had statistically significant detrimental
      effects on cognitive development. Six of the seven studies were rated weak
      quality with a high risk of bias. CONCLUSIONS: This review provides some
      preliminary evidence that physical activity may have beneficial effects on
      cognitive development during early childhood. Given the shortage of the
      information and the weak quality of available evidence, future research is needed
      to strengthen the evidence base in this area.

PMID- 26197944
TI  - Osmium(II) polypyridyl polyarginine conjugate as a probe for live cell imaging; a
      comparison of uptake, localization and cytotoxicity with its ruthenium(II)
      analogue.
AB  - A first investigation into the application of a luminescent osmium(ii) bipyridine
      complex to live cell imaging is presented. Osmium(ii) (bis-2,2-bipyridyl)-2(4
      carboxylphenyl) imidazo[4,5f][1,10]phenanthroline was prepared and conjugated to
      octaarginine, a cell penetrating peptide. The photophysics, cell uptake and
      cytotoxicity of this osmium complex conjugate were performed and compared with
      its ruthenium analogue. Cell uptake and distribution of both ruthenium and osmium
      conjugates were very similar with rapid transmembrane transport of the osmium
      probe (complete within approx. 20 min) and dispersion throughout the cytoplasm
      and organelles. The near-infrared (NIR) emission of the osmium complex (lambdamax
      726 nm) coincides well with the biological optical window and this facilitated
      luminescent and luminescence lifetime imaging of the cell which was well resolved
      from cell autofluorescence. The large Stokes shift of the emission also permitted
      resonance Raman mapping of the dye within CHO cells. Rather surprisingly, the
      osmium conjugate exhibited very low cytotoxicity when incubated both in the dark
      and under visible irradiation. This was attributed to the remarkable stability of
      this complex which was reflected by the complete absence of photo-bleaching of
      the complex even under extended continuous irradiation. In addition, when
      compared to its ruthenium analogue its luminescence was short-lived in water
      therefore rendering it insensitive to O2. 

PMID- 26197946
TI  - STR allele sequence variation: Current knowledge and future issues.
AB  - This article reviews what is currently known about short tandem repeat (STR)
      allelic sequence variation in and around the twenty-four loci most commonly used
      throughout the world to perform forensic DNA investigations. These STR loci
      include D1S1656, TPOX, D2S441, D2S1338, D3S1358, FGA, CSF1PO, D5S818, SE33,
      D6S1043, D7S820, D8S1179, D10S1248, TH01, vWA, D12S391, D13S317, Penta E,
      D16S539, D18S51, D19S433, D21S11, Penta D, and D22S1045. All known reported
      variant alleles are compiled along with genomic information available from
      GenBank, dbSNP, and the 1000 Genomes Project. Supplementary files are included
      which provide annotated reference sequences for each STR locus, characterize
      genomic variation around the STR repeat region, and compare alleles present in
      currently available STR kit allelic ladders. Looking to the future, STR allele
      nomenclature options are discussed as they relate to next generation sequencing
      efforts underway. 

PMID- 26197945
TI  - Extremity injuries in soldiers during the conflict in Mali: experience of Togo
      Level two Hospital.
AB  - PURPOSE: The aim of this study was to analyse war-related and non-war-related
      extremity injuries in soldiers in the Mali conflict. MATERIALS AND METHODS: This
      prospective study was performed from 1 May 1 to 31 December 2014. It concerned
      extremity injuries in soldiers treated at Togo Level 2 Hospital. RESULTS: Seventy
      nine patients with an average age of 31.19 years were assessed. Among them, 50
      were admitted after war injury and 29 from nonwar injury. Most war-related
      injuries were due to improvised explosive devices (IEDs) (36 %); road traffic
      accidents (51.72 %) were the main mechanism of non-war injury. A total of 125
      injuries were analysed. Limb fractures were identified in 37 patients (29.6 %),
      and 22 cases (59.46 %) were open fractures. Twenty-six (20.8 %) patients had soft
      tissue wounds. The other injuries were sprains (18.4 %), muscle contusions (15.2
      %), dislocations (8.8 %), traumatic amputations (4 %) and burns (3.2 %). Surgical
      debridement and external fixator application were the most frequently performed
      surgical procedures. Thirty-nine per cent of patients were evacuated to a level 3
      hospital for better care. CONCLUSION: The severity of injuries and their rapid
      treatment require orthopaedic surgeons to have high levels of surgical experience
      and knowledge pertaining to military or disaster surgical doctrine.

PMID- 26197947
TI  - Surgical resident learning styles have changed with work hours.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education instituted
      the 80-h workweek for residency programs in 2003. This presented a unique
      challenge for surgery residents who must acquire a medical and technical
      knowledge base during training. Therefore, learning should be delivered in an
      environment congruent with an individual's learning style. In this study, we
      evaluated the learning styles of general surgery residents to determine how
      learning styles changed after the implementation to the 80-h workweek. MATERIALS
      AND METHODS: Kolb learning style inventory was taken by general surgery residents
      at the University of Cincinnati's Department of Surgery, and results from 1999
      2012 were analyzed. Statistical analysis was performed using the chi-squared,
      logistic regression and Wilcoxon rank-sum test. Significance was defined as a P
      value of <0.05. RESULTS: A total of 411 responses were obtained from 115
      residents. Surgical residents were primarily converging (59.0%) and assimilating
      (19.1%) learners before 2003. However, there was a shift in predominate learning
      styles after the institution of the 80-h workweek to converging (43.9%) and
      accommodating (40.4%, P < 0.001). Surgical residents were also more likely to be
      team-based learners after the start of the 80-h workweek (odds ratio = 2.13, P =
      0.0016). CONCLUSIONS: After the institution of the 80-h workweek, most general
      surgery residents remained action-based learners. However, there was a shift
      within this majority toward a preference for team-based learning. This change
      paralleled the transition to a more team-based approach to patient care with the
      implementation of the 80-h workweek. These findings are important for surgical
      educators to consider in the development of surgical resident curriculum.

PMID- 26197948
TI  - Reassessing mechanism as a predictor of pediatric injury mortality.
AB  - BACKGROUND: The use of mechanism of injury as a predictor of injury outcome
      presents practical challenges because this variable may be missing or inaccurate
      in many databases. The purpose of this study was to determine the importance of
      mechanism of injury as a predictor of mortality among injured children. METHODS:
      The records of children (<15-y-old) sustaining a blunt injury were obtained from
      the National Trauma Data Bank. Models predicting injury mortality were developed
      using mechanism of injury and injury coding using either abbreviated injury scale
      post-dot values (low-dimensional injury coding) or injury International
      Classification of Diseases, Ninth Revision codes and their two-way interactions
      (high-dimensional injury coding). Model performance with and without inclusion of
      mechanism of injury was compared for both coding schemes, and the relative
      importance of mechanism of injury as a variable in each model type was evaluated.
      RESULTS: Among 62,569 records, a mortality rate of 0.9% was observed. Inclusion
      of mechanism of injury improved model performance when using low-dimensional
      injury coding but was associated with no improvement when using high-dimensional
      injury coding. Mechanism of injury contributed to 28% of model variance when
      using low-dimensional injury coding and <1% when high-dimensional injury coding
      was used. CONCLUSIONS: Although mechanism of injury may be an important predictor
      of injury mortality among children sustaining blunt trauma, its importance as a
      predictor of mortality depends on the approach used for injury coding. Mechanism
      of injury is not an essential predictor of outcome after injury when coding
      schemes are used that better characterize injuries sustained after blunt
      pediatric trauma.

PMID- 26197949
TI  - Residents' perception of skill decay during dedicated research time.
AB  - BACKGROUND: Surgery residents may take years away from clinical responsibilities
      for dedicated research time. As part of a longitudinal project, the study aim was
      to investigate residents' perceptions of clinical skill reduction during
      dedicated research time. Our hypothesis was that residents would perceive a
      greater potential reduction in skill during research time for procedures they
      were less confident in performing. MATERIALS AND METHODS: Surgical residents
      engaged in dedicated research training at multiple training programs participated
      in four simulated procedures: urinary catheterization, subclavian central line,
      bowel anastomosis, and laparoscopic ventral hernia (LVH) repair. Using
      preprocedure and postprocedure surveys, participants rated procedures for
      confidence and difficulty. Residents also indicated the perceived level of skills
      reduction for the four procedures as a result of time in the laboratory. RESULTS:
      Thirty-eight residents (55% female) completed the four clinical simulators.
      Participants had between 0-36 mo in a laboratory (M = 9.29 mo, standard deviation
      = 9.38). Preprocedure surveys noted lower confidence and higher perceived
      difficulty for performing the LVH repair followed by bowel anastomosis, central
      line insertion, and urinary catheterization (P < 0.05). Residents perceived the
      greatest reduction in bowel anastomosis and LVH repair skills compared with
      urinary catheterization and subclavian central line insertion (P < 0.001).
      Postprocedure surveys showed significant effects of the simulation scenarios on
      resident perception for urinary catheterization (P < 0.05) and LVH repair (P <
      0.05). CONCLUSIONS: Residents in this study expected greater skills decay for the
      procedures they had lower confidence performing and greater perceived difficulty.
      In addition, carefully adapted simulation scenarios had a significant effect on
      resident perception and may provide a mechanism for maintaining skills and
      keeping confidence grounded in experience.

PMID- 26197950
TI  - Defining quality in surgical care--finding a clear path forward.

PMID- 26197951
TI  - Sex-specific analysis of data in high-impact orthopaedic journals: how are we
      doing?
AB  - BACKGROUND: In 2001, the Institute of Medicine released a report stating that sex
      must be considered in all aspects and at all levels of biomedical research.
      Knowledge of differences between males and females in responses to treatment
      serves to improve our ability to care for our patients. QUESTIONS/PURPOSES: The
      purpose of our study was to determine (1) if there is an increase in the
      proportion of sex-specific reporting from 2000 to 2005 and to 2010; and (2)
      whether there is a proportional difference in such reporting based on journal
      type: subspecialty versus general orthopaedics. We hypothesize that assessment of
      the role of sex in outcomes has improved during the past 15 years and that the
      proportion of studies with of sex-specific analyses has increased with awareness
      of the role of sex in clinical outcomes and disease states. We additionally
      hypothesized that the reporting of sex would be similar between subspecialty and
      general orthopaedic journals. METHODS: Five high-impact orthopaedic journals,
      consisting of two general and three subspecialty journals, were chosen for
      review. Issues from even-numbered months during three calendar years (2000, 2005,
      2010) were critically assessed for the presence of sex-specific analyses and
      reporting by two separate reviewers. Retrospective and prospective clinical
      studies, with a minimum of 20 patients, were included for analysis. Cadaveric,
      biomechanical, and in vitro studies were excluded. Review articles and clinical
      studies with less than 20 patients were excluded. A total of 821 studies that met
      inclusion criteria were analyzed: 206 in 2000, 277 in 2005, and 338 in 2010.
      RESULTS: Overall, the proportion of sex-specific analyses increased during the
      three times studied (19%, 40/206, [95% CI, 0.14-0.25] of the studies in 2000;
      27%, 77/277, [95% CI, 0.23-0.33] in 2005; and 30%, 102/338, [95% CI, 0.25-0.35]
      in 2010). The increase in the proportion of sex-specific analysis was significant
      between 2000 and 2005 (p = 0.033), but was not significant between 2005 and 2010
      (p = 0.518). During each of the three specific years studied, general and
      subspecialty journals increased in the proportions that reported sex-based
      analyses, but specialty journals had significantly higher reporting rates only in
      2000 (2000: 11.9%, 13/109, [95% CI, 0.06-0.18] and 27.8%, 27/97, [95% CI, 0.19
      0.37], p = 0.004; 2005: 22.9%, 33/144, [95% CI, 0.16-0.30], and 33.1%, 44/133,
      [95% CI, 0.25-0.41], p = 0.059; 2010: 28.2%, 51/181, [95% CI, 0.22-0.35] and
      32.5%, 51/157, [95% CI, 0.25-0.40], p = 0.390). CONCLUSIONS: Our findings
      indicate that inclusion of sex-specific analysis and reporting in the orthopaedic
      literature improved during our study period, but are present in less than 1/3 of
      the studies. Although subgroup analysis and reporting are required by NIH
      guidelines, it is important that such analyses be published in non-NIH-funded
      studies to generate hypotheses regarding sex differences for subsequent research.
      These data also are important as they can be used in systematic reviews where
      large independent studies may not be available in the literature. CLINICAL
      RELEVANCE: Where evaluating conditions that affect males and females, studies
      should be designed with sufficient sample size to allow for subgroup analysis by
      sex to be performed, and they should include sex-specific differences among the a
      priori research questions.

PMID- 26197952
TI  - Should High-grade Extraosseous Osteosarcoma Be Treated With Multimodality Therapy
      Like Other Soft Tissue Sarcomas?
AB  - BACKGROUND: Extraosseous osteosarcoma is rare, and the most appropriate therapy
      is unclear because there are few studies regarding its treatment. The
      effectiveness of radiation and chemotherapy remains uncertain owing to
      conflicting results in previous reports. QUESTIONS/PURPOSES: To review our
      experience with contemporary multimodality treatment, we asked: (1) What is the
      disease-specific survival and local relapse-free survival? (2) Does American
      Joint Commission on Cancer (AJCC) stage, tumor size, or location relate to
      disease outcome? (3) Does radiation therapy improve local control or survival?
      (4) Do doxorubicin and ifosfamide improve local control or survival? METHODS:
      Between 1990 and 2012, we treated 40 patients for localized, high-grade
      extraosseous osteosarcoma. In this retrospective study, we could determine the
      status of 36 patients (90%) either to death or for a minimum of 24 months of
      followup; four (10%) were lost to followup before 24 months. There were 11
      patients with AJCC Stage IIA and 25 with Stage III disease. All patients
      underwent wide surgical excision. Of the patients with Stage IIA disease, four
      received radiation and none received chemotherapy. Of the patients with Stage III
      disease, six received radiation, seven were treated with chemotherapy, and six
      received radiation and chemotherapy. During the study period, high-dose
      doxorubicin and ifosfamide was the preferred chemotherapy regimen for patients
      younger than 60 years with normal cardiac and renal function. Local relapse-free
      survival and disease-specific survival were determined by Kaplan-Meier analysis
      using a prospectively maintained institutional database supplemented by
      information from the institutional tumor registry. The Cox proportional hazard
      model was used to determine the effect of various factors on local recurrence and
      patient survival. RESULTS: At 5 years, local relapse-free survival was 47% (95%
      CI, 27%-64%), and disease-specific survival was 53% (95% CI, 35%-68%). In
      multivariate analysis, AJCC stage, which depends on tumor size, was the strongest
      predictor of local relapse-free survival (hazard ratio [HR] = 0.17, p = 0.02),
      while tumor depth was the best predictor of disease-specific survival (HR = 5.6,
      p = 0.02). Radiation improved local relapse-free survival (HR = 0.30, p = 0.03)
      but not disease-specific survival in multivariate analysis. A regimen of
      doxorubicin and ifosfamide was associated with better local relapse-free survival
      for patients with Stage III disease (HR = 0.16, p = 0.04) but not disease
      specific survival (HR = 0.32, p = 0.08). CONCLUSIONS: With the limited number of
      patients in our study, it appears that extraosseous osteosarcoma behaves
      differently than osteosarcoma of bone. Multimodality treatment that includes
      doxorubicin and ifosfamide-based chemotherapy, radiation, and surgery may be a
      valid therapeutic strategy for Stage III disease, but larger, prospective studies
      will be needed to verify our preliminary observations. LEVEL OF EVIDENCE: Level
      III, therapeutic study.

PMID- 26197953
TI  - Split dose carbon ion irradiation of the rat spinal cord: Dependence of the
      relative biological effectiveness on dose and linear energy transfer.
AB  - PURPOSE: To measure the relative biological effectiveness (RBE) of carbon ions
      relative to 15 MeV photons in the rat spinal cord for different linear energy
      transfers (LET) to validate model calculations. METHODS AND MATERIALS: The
      cervical spinal cord of rats was irradiated with 2 fractions of carbon ions at
      six positions of a 6 cm spread-out Bragg-peak (SOBP, 16-99 keV/MUm). TD50-values
      (dose at 50% complication probability) were determined from dose-response curves
      for the endpoint radiation induced myelopathy (paresis grade II) within 300 days
      after irradiation. Using previously published TD50-values for photons (Karger et
      al., 2006; Debus et al., 2003), RBE-values were determined and compared with
      predictions of two versions of the local effect model (LEM I and IV). RESULTS:
      TD50-values for paresis grade II were 26.7 +/- 0.4 Gy (16 keV/MUm), 24.0 +/- 0.3
      Gy (21 keV/MUm), 22.5 +/- 0.3 Gy (36 keV/MUm), 20.1 +/- 1.2 Gy (45 keV/MUm), 17.7
      +/- 0.3 Gy (66 keV/MUm), and 14.9 +/- 0.3 Gy (99 keV/MUm). RBE-values increased
      from 1.28 +/- 0.03 (16 keV/MUm) up to 2.30 +/- 0.06 at 99 keV/MUm. At the applied
      high fractional doses, LEM I fits best at 16 keV/MUm and deviates progressively
      toward higher LETs while LEM IV agrees best at 99 keV/MUm and shows increasing
      deviations, especially below 66 keV/MUm. CONCLUSIONS: The measured data improve
      the knowledge on the accuracy of RBE-calculations for carbon ions.

PMID- 26197954
TI  - Influence of puberty and antral follicle count on calving day in crossbred beef
      heifers.
AB  - Lifetime productivity and longevity are greater in beef cows that give birth
      early in their first calving season. The ability of heifers to conceive early in
      the breeding season is traditionally thought to be a function of pubertal status;
      however, recent evidence suggests that antral follicle count is positively
      associated with calving day in pubertal beef heifers. Additionally, there is
      evidence to suggest that the total number of ovarian follicles may alter response
      to hormonal synchronization protocols. The objectives of this study were to
      confirm the beneficial influence of antral follicle count on calving day in beef
      heifers and to determine whether response to PGF2alpha is associated with
      differences in antral follicle counts. A 2 * 2 factorial experiment was designed
      to investigate the interaction between calving period (early vs. late) and
      PGF2alpha (control vs. PGF) on calving day and antral follicle count in yearling
      beef heifers (n = 95). As intended, calving day was less in the early calving
      period compared to the late calving period (P < 0.01). There were no differences
      in calving day in response to treatment with PGF2alpha (P > 0.05). There was a
      significant interaction between calving period and PGF2alpha on age at first
      calving (P < 0.01), such that heifers treated with PGF2alpha that gave birth
      early were younger than heifers treated with saline that gave birth early. Calf
      weaning weights were greater in the early calving group than in the late calving
      group (P < 0.01). Heifers that gave birth in the early calving group possessed
      more antral follicles at prebreeding ultrasonographic examination than heifers
      that gave birth in the late calving group (P = 0.05). These findings confirm that
      antral follicle counts are associated with calving day in pubertal beef heifers.
      The use of antral follicle counts as a prebreeding phenotype provides additional
      utility to reproductive tract scoring for commercial production because of its
      association with calving day. As a prebreeding ovarian phenotype, antral follicle
      counts may hold additional applicability for organic beef producers looking to
      reduce the length of their calving season without increasing the total number of
      replacement heifers retained.

PMID- 26197955
TI  - HypoxamiRs: regulators of cardiac hypoxia and energy metabolism.
AB  - Hypoxia and its intricate regulation are at the epicenter of cardiovascular
      research. Mediated by hypoxia-inducible factors as well as by several microRNAs,
      recently termed 'hypoxamiRs', hypoxia affects several cardiac pathophysiological
      processes. Hypoxia is the driving force behind the regulation of the
      characteristic metabolic switch from predominant fatty acid oxidation in the
      healthy heart to glucose utilization in the failing myocardium, but also
      instigates reactivation of the fetal gene program, induces the cardiac
      hypertrophy response, alters extracellular matrix composition, influences
      mitochondrial biogenesis, and impacts upon myocardial contractility. HypoxamiR
      regulation adds a new level of complexity to this multitude of hypoxia-mediated
      effects, rendering the understanding of the hypoxic response a fundamental piece
      in solving the cardiovascular disease puzzle. 

PMID- 26197956
TI  - Paleolimnological record as an indication of incipient eutrophication in an
      oligotrophic subtropical coastal lake in Southern Brazil.
AB  - Paleolimnology of lake sediments can be a powerful tool to assess various aspects
      of lake history and catchment change through elemental, isotopic and molecular
      analysis of the sedimented organic matter (OM). In this sense, the objective of
      the present study was to investigate the source, depositional history and
      preservation of OM in the sediments of two different sites in Peri Lake (southern
      Brazil) to better understand the nature and direction of environmental changes.
      Therefore, two sediment cores were sampled and analysed for total organic carbon
      (TOC), total nitrogen (TN) and total phosphorus (TP) concentrations and elemental
      ratios, and stable isotope ratios of C and N (delta(13)C and delta(15)N). Both
      cores showed similar general tendencies, with increasing amounts of OM (range 1
      35%), TOC (2.55-258.40 mg g(-1)), TN (0.30-25.97 mg g(-1)) and TP (0.03-4.72 mg
      g(-1)) from the bottom toward the top more recent layers. TOC:TN ratios (range
      8.1-14.7) showed a slight decrease in recent times and indicated a mixture of
      allochthonous and autochthonous contribution to the OM, with predominance of the
      last source. TN:TP (range 0.2-51.3) indicated a condition of potential limitation
      by P in general. Both delta(13)C (range -25.58 to -20.85) and delta(15)N (range
      2.6 to 7.1) showed a decreasing pattern toward the top of the cores, in
      opposition to macronutrient concentration. Differences in the depth variation
      pattern between the two cores were associated to the marginal location of one of
      the cores. The results suggest that nutrients and primary production are
      increasing in the lake.

PMID- 26197957
TI  - [Effect of Hypericin on the Function of the Neuroretina: An Electroretinographic
      Study].
AB  - BACKGROUND: Hypericin is an important component of the Saint John's wort
      (Hypericum perforatum). It is assumed to inhibit intracellular signalling
      cascades, which contribute to neoangiogenesis. The phototoxic effect of hypericin
      on the retina was investigated in human retinal pigment epithelium (RPE);
      hypericin induces oxidative stress and has also been described to be an inhibitor
      of Ca(2+) influx channel in cultured RPE cells. The aim of our study is to
      evaluate the effect of hypericine on the function of the neuroretina. METHODS:
      Isolated bovine retinas were perfused with an oxygen saturated nutrient solution
      (1 mL/min). We exposed the retina to a flashlight of 6.3 mlx every 5 min. The
      electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl
      electrodes. ERGs were monitored before, during and after hypericin exposure.
      RESULTS: In three independent experiments we investigated the effect of hypericin
      on the amplitude of the b-wave. In our experiments we observed a significant
      reduction of the amplitude of the b-wave to 87.1 +/- 3.5 % (p = 0.02). This
      reduction was in all our experiments partially reversible. After hypericin wash
      out the b-wave amplitude did not recover completely and did not return to the
      initial value (91.0 +/- 5.1 %; not significant). We did not observe a significant
      effect of hypericin on the implicit time of the b-wave. CONCLUSION: This study
      shows for the first time that hypericin influences retinal signal transduction,
      suggesting that hypericin impairs not only the RPE, but also affects retinal
      signalling and function.

PMID- 26197958
TI  - [Comparison of Intravitreal Dexamethasone Implant versus Intravitreal Ranibizumab
      as a First-Line Treatment of Macular Oedema due to Retinal Vein Occlusion].
AB  - PURPOSE: The present study investigated the treatment effect of dexamethasone
      implant (Ozurdex(r), group 1) and anti-VEGF injection (Lucentis(r), group 2) in
      course of macular oedema due to retinal vein occlusion in a retrospective, non
      randomised case series. MATERIAL AND METHODS: Group 1 comprised 60 patients (31
      with CRVO and 29 with BRVO) and group 2 included 52 patients, 27 with CRVO and 25
      with BRVO) and both groups were further treated in case of recurrence.
      Preoperative and in monthly intervals best corrected visual acuity (BCVA),
      central retinal thickness using SD-OCT (Spectralis, Heidelberg Engineering),
      intraocular pressure, biomicroscopy status and a fundus photo documentation
      (Optomap) were evaluated. The primary clinical endpoint was visual acuity 12
      months after the first intravitreal therapy, while secondary endpoints included
      the central retinal thickness change and safety of therapy. RESULTS: In group 1,
      an increase of BCVA (+/- standard deviation) of 8.4 (+/- 1.9) letters was
      observed in CRVO patients and a gain of 10.7 (+/- 3.8) letters in BRVO patients
      after 12 months, while in group 2, an increase of BCVA of 6.9 (+/- 1.9) letters
      (CRVO) compared to 12.5 (+/- 3.7) letters (BRVO) was observed after the same time
      span. In both groups a significant reduction in retinal thickness was achieved.
      An increase of intraocular pressure above 5 mmHg was observed in nearly half of
      the cases In group 1, but was well controlled by conservative antiglaucomatous
      therapy. We observed a progression of lens opacity in approximately 50 % of the
      cases in group 1. CONCLUSION: The treatment with Ozurdex compared to Lucentis
      appears to provide a trend towards a better although not significant visual
      acuity increase after 12 months in CRVO patients. A similar trend favouring anti
      VEGF treatment with Lucentis was seen in patients with BRVO. However, the lens
      status and age of the patient should be taken into account when considering a
      treatment with Ozurdex.

PMID- 26197959
TI  - Do PFNA devices and Intertan nails both have the same effects in the treatment of
      trochanteric fractures? A prospective clinical study.
AB  - OBJECTIVE: To clinically and radiologically compare third-generation
      intramedullary nails used in the treatment of trochanteric hip fractures and to
      determine their efficacy. MATERIALS AND METHODS: Seventy-five of 88 patients
      admitted to our hospital with trochanteric fractures were enrolled in the study;
      43 were treated with PFNA devices and 32 with Intertan nails. The amount of
      compression applied during the procedure, duration of the procedure, amount of
      subsequent shortening in the proximal femoral area, subsequent backup of proximal
      screws, and changes in the tip-apex and tip-cortex distances were compared
      between groups. The postoperative change in the varus angle of the proximal femur
      and times to mobilization, full weight bearing, and fracture union were also
      evaluated. RESULTS: On early postoperative radiographs, the tip-apex distance was
      <=25 mm in 86 % of patients in the PFNA group and 96.9 % of those in the Intertan
      group. Twelve months postoperatively, the tip-apex distance did not differ
      between groups. No cut-out of the screws into the coxofemoral joint was observed.
      Fracture healing was achieved in all patients. At 12 months postoperatively, the
      rates of proximal screw backup, proximal femoral shortening, and decrease in the
      varus angle of the proximal femur were significantly higher in the PFNA group
      than in the Intertan group. CONCLUSIONS: Trochanteric fractures may be treated
      effectively with PFNA devices or Intertan nails. During the healing period, the
      rates of reverse displacement of the proximal screw, shortening of the proximal
      femur, and decrease in the varus angle of the proximal femur were significantly
      higher in the PFNA group than in the Intertan group. Surgical technique, implant
      positioning, and the choice of implant play roles in the successful treatment of
      trochanteric fractures. LEVEL OF EVIDENCE: Level 1, prospective, prognostic
      study.

PMID- 26197960
TI  - Sonographic evaluation of effects of the volar plate on trigger finger.
AB  - BACKGROUND: We evaluated trigger fingers ultrasonographically and clarified
      differences between fingers with and without continuous locking or snapping
      symptoms according to the thicknesses of the A1 pulley, flexor tendon and volar
      plate. METHODS: We evaluated 26 trigger fingers, divided into two groups: Group
      1, 14 fingers with locking or snapping; and Group 2, 12 fingers without such
      symptoms. We also evaluated 26 contralateral fingers as controls (Control 1 and 2
      groups). We compared each group to the respective control group according to
      thickness of the A1 pulley and volar plate, and cross-sectional area of the
      flexor tendon. In addition, nine fingers with locking or snapping and treated
      using corticosteroid injection were evaluated according to symptoms and
      sonographic findings 3-4 weeks after treatment. RESULTS: Thickness of the A1
      pulley and cross-sectional area of the flexor tendon were greater in both Groups
      1 and 2 than in controls. Thickness of the volar plate was greater in Group 1
      than in Control 1, although no significant difference was seen between Group 2
      and Control 2. In Group 1, eight of the nine fingers showed an alleviation of
      locking or snapping symptoms with corticosteroid injection, and sonographic
      findings showed that thickness of the volar plate was significantly decreased
      with corticosteroid injection, in addition to reduced thickness of the A1 pulley.
      CONCLUSION: In addition to thickening of the A1 pulley, thickening of the volar
      plate may represent an important contributor to continuous snapping or locking
      symptoms.

PMID- 26197965
TI  - Enhanced metastasis in RNF13 knockout mice is mediated by a reduction in GM-CSF
      levels.
AB  - RING finger protein 13 (RNF13) is a novel E3 ubiquitin ligase whose expression is
      associated with cancer development. However, its specific role in cancer
      progression and metastasis remains unclear. Here, a B16F10/LLC experimental
      pulmonary metastatic model was developed to examine the formation of metastatic
      foci in the lung. A greater number of tumor colonies were observed in the lungs
      of RNF13-knockout (KO) mice than in their wild-type (WT) littermates, whereas no
      significant differences in tumor size were observed between the two groups. In
      short-term experiments, the number of fluorescently-labeled B16F10 cells
      increased remarkably in RNF13-KO lungs at early time points, whereas clearance of
      tumor cells from the blood was not affected. These results indicated that RNF13
      may inhibit the colonization of B16F10 cells in the lung. Assessment of the
      concentration of various cytokines in tumor bearing lungs and blood did not
      detect significant differences between the blood of RNF13-KO and WT mice; however
      the levels of GM-CSF were significantly reduced in RNF13-KO tumor bearing lungs,
      which may have guided more B16F10 cells to migrate to the lungs. This was
      confirmed by lower GM-CSF concentrations in conditioned media from the culture of
      RNF13-KO lung slices. Collectively, our results suggest that host RNF13 affects
      the concentration of GM-CSF in tumor-bearing lungs, leading to a reduction in the
      colonization of metastatic tumor cells in the lung.

PMID- 26197966
TI  - Co-localization of Gamma-Aminobutyric Acid and Glutamate in Neurons of the Spider
      Central Nervous System.
AB  - Spider sensory neurons with cell bodies close to various sensory organs are
      innervated by putative efferent axons from the central nervous system (CNS).
      Light and electronmicroscopic imaging of immunolabeled neurons has demonstrated
      that neurotransmitters present at peripheral synapses include gamma-aminobutyric
      acid (GABA), glutamate and octopamine. Moreover, electrophysiological studies
      show that these neurotransmitters modulate the sensitivity of peripheral sensory
      neurons. Here, we undertook immunocytochemical investigations to characterize
      GABA and glutamate-immunoreactive neurons in three-dimensional reconstructions of
      the spider CNS. We document that both neurotransmitters are abundant in
      morphologically distinct neurons throughout the CNS. Labeling for the vesicular
      transporters, VGAT for GABA and VGLUT for glutamate, showed corresponding
      patterns, supporting the specificity of antibody binding. Whereas some neurons
      displayed strong immunolabeling, others were only weakly labeled. Double labeling
      showed that a subpopulation of weakly labeled neurons present in all ganglia
      expresses both GABA and glutamate. Double labeled, strongly and weakly labeled
      GABA and glutamate immunoreactive axons were also observed in the periphery along
      muscle fibers and peripheral sensory neurons. Electron microscopic investigations
      showed presynaptic profiles of various diameters with mixed vesicle populations
      innervating muscle tissue as well as sensory neurons. Our findings provide
      evidence that: (1) sensory neurons and muscle fibers are innervated by
      morphologically distinct, centrally located GABA- and glutamate immunoreactive
      neurons; (2) a subpopulation of these neurons may co-release both
      neurotransmitters; and (3) sensory neurons and muscles are innervated by all of
      these neurochemically and morphologically distinct types of neurons. The
      biochemical diversity of presynaptic innervation may contribute to how spiders
      filter natural stimuli and coordinate appropriate response patterns. 

PMID- 26197967
TI  - Soot and house dust mite allergen cause eosinophilic laryngitis in an animal
      model.
AB  - OBJECTIVES/HYPOTHESIS: Chronic laryngitis (CL) is common and costly. One of the
      most common causes of CL is thought to be laryngopharyngeal reflux, although a
      significant percentage of individuals fail to get better with acid suppressive
      therapy. The role of other potential causes of CL such as allergy and
      environmental pollution has not been thoroughly investigated. PURPOSE: To
      evaluate the association between iron soot, house dust mite allergen (HDMA), and
      CL in an established animal model. METHODS: Twenty-four guinea pigs were
      separated into four 6-week exposure groups: 1) saline (allergen control) +
      filtered air (pollution control); 2) HDMA (Dermatophygoides farinae) + filtered
      air; 3) saline + combustion particulates; or 4) HDMA + combustion particulates.
      The primary outcome measure was mean eosinophil profile (MEP) in glottic,
      subglottic, and trachea epithelium and submucosa. RESULTS: The combination of
      iron soot and HDMA caused eosinophilia (elevated MEP) in the glottic (P < 0.06),
      subglottic (P < 0.05), and trachea (P < 0.05) submucosa and epithelium (P <
      0.05). CONCLUSION: The combination of HDMA and iron soot resulted in laryngeal
      eosinophilia in an established guinea pig model of CL. The data support the
      notion that factors other than reflux may cause CL. Further investigation into
      eosinophilic laryngitis as a distinct clinical entity caused by exposure to
      environmental allergen and pollution is warranted.

PMID- 26197968
TI  - A new voluntary blood collection method for the Andean bear (Tremarctos ornatus)
      and Asiatic black bear (Ursus thibetanus).
AB  - Various training methods have been developed for animal husbandry and health care
      in zoos and one of these trainings is blood collection. One training method,
      recently widely used for blood collection in Ursidae, requires setting up a
      sleeve outside the cage and gives access to limited blood collection sites. A new
      voluntary blood collection method without a sleeve was applied to the Andean bear
      (Tremarctos ornatus) and Asiatic black bear (Ursus thibetanus) with access to
      various veins at the same time. The present study evaluated the effectiveness of
      this new method and suggests improvements. Two Andean and two Asiatic black bears
      in Yokohama and Nogeyama Zoological Gardens, respectively, were trained to hold a
      bamboo pipe outside their cages. We could, thereby, simultaneously access
      superficial dorsal veins, the dorsal venous network of the hand, the cephalic
      vein from the carpal joint, and an area approximately 10 cm proximal to the
      carpal joint. This allowed us to evaluate which vein was most suitable for blood
      collection. We found that the cephalic vein, approximately 10 cm proximal to the
      carpal joint, was the most suitable for blood collection. This new method
      requires little or no modification of zoo facilities and provides a useful
      alternative method for blood collection. It could be adapted for use in other
      clinical examinations such as ultrasound examination.

PMID- 26197970
TI  - Deployment of regulatory genes during gastrulation and germ layer specification
      in a model spiralian mollusc Crepidula.
AB  - BACKGROUND: During gastrulation, endoderm and mesoderm are specified from a
      bipotential precursor (endomesoderm) that is argued to be homologous across
      bilaterians. Spiralians also generate mesoderm from ectodermal precursors
      (ectomesoderm), which arises near the blastopore. While a conserved gene
      regulatory network controls specification of endomesoderm in deuterostomes and
      ecdysozoans, little is known about genes controlling specification or behavior of
      either source of spiralian mesoderm or the digestive tract. RESULTS: Using the
      mollusc Crepidula, we examined conserved regulatory factors and compared their
      expression to fate maps to score expression in the germ layers, blastopore lip,
      and digestive tract. Many genes were expressed in both ecto- and endomesoderm,
      but only five were expressed in ectomesoderm exclusively. The latter may
      contribute to epithelial-to-mesenchymal transition seen in ectomesoderm.
      CONCLUSIONS: We present the first comparison of genes expressed during spiralian
      gastrulation in the context of high-resolution fate maps. We found variation of
      genes expressed in the blastopore lip, mouth, and cells that will form the anus.
      Shared expression of many genes in both mesodermal sources suggests that
      components of the conserved endomesoderm program were either co-opted for
      ectomesoderm formation or that ecto- and endomesoderm are derived from a common
      mesodermal precursor that became subdivided into distinct domains during
      evolution.

PMID- 26197971
TI  - Promoting Good Psychiatric Management for Patients With Borderline Personality
      Disorder.
AB  - General psychiatric management for patients with borderline personality disorder
      was devised to be an outpatient intervention that could be readily learned and
      easily delivered by independent community mental health professionals. To
      disseminate the approach, Drs. Gunderson and Links developed the Handbook of Good
      Psychiatric Management for Borderline Personality Disorder (Gunderson & Links, )
      that presented the basics of the approach, videos to illustrate the appropriate
      clinical skills, and case examples to practice adherence to the approach.
      Unfortunately, the inclusion of "psychiatric" in the treatment's name may
      discourage psychologists and other mental health professionals from using this
      therapy. In this article, we review the basic principles and approaches related
      to general psychiatric management. With a case example, we illustrate how
      psychologists can use all the general psychiatric management principles for their
      patients with BPD, except medications and, as a result, provide and deliver this
      approach effectively. 

PMID- 26197969
TI  - Functional recovery in new mouse models of ALS/FTLD after clearance of
      pathological cytoplasmic TDP-43.
AB  - Accumulation of phosphorylated cytoplasmic TDP-43 inclusions accompanied by loss
      of normal nuclear TDP-43 in neurons and glia of the brain and spinal cord are the
      molecular hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal
      lobar degeneration (FTLD-TDP). However, the role of cytoplasmic TDP-43 in the
      pathogenesis of these neurodegenerative TDP-43 proteinopathies remains unclear,
      due in part to a lack of valid mouse models. We therefore generated new mice with
      doxycycline (Dox)-suppressible expression of human TDP-43 (hTDP-43) harboring a
      defective nuclear localization signal (?NLS) under the control of the
      neurofilament heavy chain promoter. Expression of hTDP-43?NLS in these
      'regulatable NLS' (rNLS) mice resulted in the accumulation of insoluble,
      phosphorylated cytoplasmic TDP-43 in brain and spinal cord, loss of endogenous
      nuclear mouse TDP-43 (mTDP-43), brain atrophy, muscle denervation, dramatic motor
      neuron loss, and progressive motor impairments leading to death. Notably,
      suppression of hTDP-43?NLS expression by return of Dox to rNLS mice after disease
      onset caused a dramatic decrease in phosphorylated TDP-43 pathology, an increase
      in nuclear mTDP-43 to control levels, and the prevention of further motor neuron
      loss. rNLS mice back on Dox also showed a significant increase in muscle
      innervation, a rescue of motor impairments, and a dramatic extension of lifespan.
      Thus, the rNLS mice are new TDP-43 mouse models that delineate the timeline of
      pathology development, muscle denervation and neuron loss in ALS/FTLD-TDP.
      Importantly, even after neurodegeneration and onset of motor dysfunction, removal
      of cytoplasmic TDP-43 and the concomitant return of nuclear TDP-43 led to neuron
      preservation, muscle re-innervation and functional recovery. 

PMID- 26197972
TI  - Patient Experience in Single Rooms Compared with the Open Ward for Elective
      Orthopaedic Admissions.

PMID- 26197973
TI  - Mapping Local Cytosolic Enzymatic Activity in Human Esophageal Mucosa with Porous
      Silicon Nanoneedles.
AB  - Porous silicon nanoneedles can map Cathepsin B activity across normal and tumor
      human esophageal mucosa. Assembling a peptide-based Cathepsin B cleavable sensor
      over a large array of nano-needles allows the discrimination of cancer cells from
      healthy ones in mixed culture. The same sensor applied to tissue can map
      Cathepsin B activity with high resolution across the tumor margin area of
      esophageal adenocarcinoma. 

PMID- 26197974
TI  - An improved method for the determination of 5-hydroxymethylfurfural in Shenfu
      injection by direct analysis in real time-quadrupole time-of-flight mass
      spectrometry.
AB  - The emergence of direct analysis in real time (DART) ion source provides the
      great possibility for rapid analysis of hazardous substance in drugs. DART mass
      spectrometry (DART-MS) enabled the conducting of a fast and non-contact analysis
      of various samples, including solid or liquid ones, without complex sample
      preparation or chromatographic separation. In this study, a modified DART
      quadrupole time-of-flight mass spectrometry (DART-QTOF-MS) method was developed
      for identification and determination of 5-hydroxymethylfurfural (5-HMF) in Shenfu
      (SF) injection. The quantitative transfer of sample solution was introduced to
      the glass tips of DIP-it sampler at a fixed volume, which significantly increases
      the repeatability and accuracy of analytical results. The protonated ion of
      dibutyl phthalate in the atmosphere was used as the reference mass for TOF-MS
      recalibration during the data acquisition for constant high accuracy mass
      measurements. Finally, the developed DART-MS method was used to determine 5-HMF
      in seven batches of SF injection, and the contents of 5-HMF were not higher than
      100 ug/mL. The results obtained were further confirmed by an ultra-high
      performance liquid chromatography combined with triple quadrupole mass
      spectrometer (UHPLC-QQQ-MS). The overall results demonstrated that the DART-QTOF
      MS method could be applied as an alternative technique for rapid monitoring 5-HMF
      in herbal medicine injection. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26197976
TI  - Headache disorders and public ill-health in India: prevalence estimates in
      Karnataka State.
AB  - BACKGROUND: Primary headache disorders are among the commonest disorders,
      affecting people in all countries. India appears to be no exception, although
      reliable epidemiological data on headache in this highly populous country are not
      available. Such information is needed for health-policy purposes. Our aim was to
      estimate the prevalence of each of the headache disorders of public-health
      importance, and examine their sociodemographic associations, in urban and rural
      populations of Karnataka, south India. METHODS: In a door-to-door survey, 2,329
      biologically unrelated adults (aged 18-65 years) were randomly sampled from urban
      (n = 1,226) and rural (n = 1,103) areas in and around Bangalore and interviewed
      by trained researchers using a pilot-tested, validated, structured questionnaire.
      ICHD-II diagnostic criteria were applied. RESULTS: The observed 1-year prevalence
      of any headache was 63.9 %, with a female preponderance of 4:3. The age
      standardised 1 year prevalence of migraine was 25.2%; prevalence was higher among
      females than males (OR: 2.1 [1.7-2.6]) and among those from rural areas than
      urban (OR = 1.5 [1.3-1.8]). The age-standardized 1 year prevalence of TTH was
      35.1%, higher among younger people. The estimated prevalence of all headache on
      >=15 days/month was 3.0%; that of pMOH was 1.2%, five-times greater among females
      than males and with a rural preponderance. CONCLUSIONS: There is a very high 1
      year prevalence of migraine in south India (the mean global prevalence is
      estimated at 14.7%). Explanations probably lie in cultural, lifestyle and/or
      environmental factors, although the observed associations with female gender and
      rural dwelling are usual. Levels of TTH, pMOH and other headache on >=15
      days/month are similar to global averages, while the very strong association of
      pMOH with female gender requires explanation. Until another study is conducted in
      the north of the country, these are the best data available for health policy in
      a population of over 1.2 billion people.

PMID- 26197975
TI  - Muscle pain sensitivity after glutamate injection is not modified by systemic
      administration of monosodium glutamate.
AB  - BACKGROUND: Monosodium glutamate (MSG) is often thought to be associated with
      headache and craniofacial pains like temporomandibular disorders. This
      randomized, double-blinded, placebo-controlled study was performed to investigate
      how ingestion of MSG affects muscle pain sensitivity before and after
      experimentally induced muscle pain. METHODS: Sixteen healthy adult subjects
      participated in 2 sessions with at least 1-week interval between sessions. In
      each session, two injections of glutamate (Glu, 0.5 M, 0.2 ml) and two injections
      of saline (0.9%, 0.2 ml) into the masseter and temporalis muscles, respectively,
      were undertaken, with a 15 min interval between each injection. Injections of
      saline were made contralateral to Glu injections and done in a randomized order.
      Participants drank 400 mL of soda mixed with either MSG (150 mg/kg) or NaCl (24
      mg/kg, placebo) 30 min before the intramuscular injections. Pressure pain
      thresholds (PPT), autonomic parameters and pain intensity were assessed prior to
      (baseline) and 30 min after ingestion of soda, as well as 5 min and 10 min after
      the intramuscular injections and at the end of the session. Whole saliva samples
      were collected prior to and 30, 45, 60, and 75 min after the ingestion of soda.
      RESULTS: MSG administration resulted in a significantly higher Glu level in
      saliva than administration of NaCl and was associated with a significant increase
      in systolic blood pressure. Injections of Glu were significantly more painful
      than injections of NaCl. However, ingestion of MSG did not change the intensity
      of Glu-evoked pain. Glu injections also significantly increased systolic and
      diastolic blood pressure, but without an additional effect of MSG ingestion. Glu
      injections into the masseter muscle significantly reduced the PPT. However, pre
      injection MSG ingestion did not significantly alter this effect. Interestingly,
      PPT was significantly increased in the trapezius after MSG ingestion and
      intramuscular injection of Glu in the jaw muscles. CONCLUSION: The main finding
      in this study was that systemic intake of a substantial amount of MSG does not
      influence either pain intensity or pressure pain sensitivity in the masseter and
      temporalis muscles into which Glu injections were made.

PMID- 26197977
TI  - Transcutaneous supraorbital neurostimulation in "de novo" patients with migraine
      without aura: the first Italian experience.
AB  - BACKGROUND: Transcutaneous supraorbital neurostimulation (tSNS) has been recently
      found superior to sham stimulation for episodic migraine prevention in a
      randomized trial. We evaluated both the safety and efficacy of a brief period of
      tSNS in a group of patients with migraine without aura (MwoA). METHODS: We
      enrolled 24 consecutive patients with MwoA experiencing a low frequency of
      attacks, which had never taken migraine preventive drugs in the course of their
      life. Patients performed a high frequency tSNS and were considered "compliant" if
      they used the tSNS for >= 2/3 of the total time expected. For this reason, four
      patients were excluded from the final statistical analysis. Primary outcome
      measures were the reduction migraine attacks and migraine days per month (p <
      0.05). Furthermore, we evaluated the percentage of patients having at least 50%
      reduction of monthly migraine attacks and migraine days. Secondary outcome
      measures were the reduction of headache severity during migraine attacks and HIT
      6 (Headache Impact Test) rating as well as in monthly intake of rescue medication
      (p < 0.05). Finally, compliance and satisfaction to treatment and potential
      adverse effects related to tSNS have been evaluated. RESULTS: Between run-in and
      second month of tSNS treatment, both primary and secondary endpoints were met.
      Indeed, we observed a statistically significant decrease in the frequency of
      migraine attacks (p < 0.001) and migraine days (p < 0.001) per month. We also
      demonstrated at least 50% reduction of monthly migraine attacks and migraine days
      in respectively 81 and 75% of patients. Furthermore, a statistically significant
      reduction in average of pain intensity during migraine attacks (p = 0.002) and
      HIT-6 rating (p < 0.001) and intake of rescue medication (p < 0.001) has been
      shown. All patients showed good compliance levels and no relevant adverse events.
      CONCLUSION: In patients experiencing a low frequency of attacks, significant
      improvements in multiple migraine severity parameters were observed following a
      brief period of high frequency tSNS. Therefore, tSNS may be considered a valid
      option for the preventive treatment of migraine attacks in patients who cannot or
      are not willing to take daily medications, or in whom low migraine frequency
      and/or intensity would not require pharmacological preventive therapies.

PMID- 26197978
TI  - Pathogenic CWF19L1 variants as a novel cause of autosomal recessive cerebellar
      ataxia and atrophy.
AB  - Autosomal recessive cerebellar ataxia (ARCA) is a group of neurological disorders
      characterized by degeneration or abnormal development of the cerebellum and
      spinal cord. ARCA is clinically and genetically highly heterogeneous, with over
      20 genes involved. Exome sequencing of a girl with ARCA from non-consanguineous
      Dutch parents revealed two pathogenic variants c.37G>C; p.D13H and c.946A>T;
      p.K316* in CWF19L1, a gene with an unknown function, recently reported to cause
      ARCA in a Turkish family. Sanger sequencing showed that the c.37G>C variant was
      inherited from the father and the c.946A>T variant from the mother. Pathogenicity
      was based on the damaging effect on protein function as the c.37G>C variant
      changed the highly conserved, negatively charged aspartic acid to the positively
      charged histidine and the c.946A>T variant introduced a premature stop codon. In
      addition, 27 patients with ARCA were tested for pathogenic variants in CWF19L1,
      however, no pathogenic variants were identified. Our data confirm CWF19L1 as a
      novel but rare gene causing ARCA. 

PMID- 26197979
TI  - Exome sequencing identifies recessive CDK5RAP2 variants in patients with isolated
      agenesis of corpus callosum.
AB  - Agenesis of the corpus callosum (ACC) is a common brain malformation which can be
      observed either as an isolated condition or as part of numerous congenital
      syndromes. Therefore, cognitive and neurological involvements in patients with
      ACC are variable, from mild linguistic and behavioral impairments to more severe
      neurological deficits. To date, the underlying genetic causes of isolated ACC
      remains elusive and causative genes have yet to be identified. We performed exome
      sequencing on three acallosal siblings from the same non-consanguineous family
      and identified compound heterozygous variants, p.[Gly94Arg];[Asn1232Ser], in the
      protein encoded by the CDK5RAP2 gene, also known as MCPH3, a gene previously
      reported to cause autosomal recessive primary microcephaly. Our findings suggest
      a novel role for this gene in the pathogenesis of isolated ACC. 

PMID- 26197980
TI  - A recurrent copy number variation of the NEB triplicate region: only revealed by
      the targeted nemaline myopathy CGH array.
AB  - Recently, new large variants have been identified in the nebulin gene (NEB)
      causing nemaline myopathy (NM). NM constitutes a heterogeneous group of disorders
      among the congenital myopathies, and disease-causing variants in NEB are a main
      cause of the recessively inherited form of NM. NEB consists of 183 exons and it
      includes homologous sequences such as a 32-kb triplicate region (TRI), where
      eight exons are repeated three times (exons 82-89, 90-97, 98-105). In human, the
      normal copy number of NEB TRI is six (three copies in each allele). Recently, we
      described a custom NM-CGH microarray designed to detect copy number variations
      (CNVs) in the known NM genes. The array has now been updated to include all the
      currently known 10 NM genes. The NM-CGH array is superior in detecting CNVs,
      especially of the NEB TRI, that is not included in the exome capture kits. To
      date, we have studied 266 samples from 196 NM families using the NM-CGH
      microarray, and identified a novel recurrent NEB TRI variation in 13% (26/196) of
      the families and in 10% of the controls (6/60). An analysis of the breakpoints
      revealed adjacent repeat elements, which are known to predispose for
      rearrangements such as CNVs. The control CNV samples deviate only one copy from
      the normal six copies, whereas the NM samples include CNVs of up to four
      additional copies. Based on this study, NEB seems to tolerate deviations of one
      TRI copy, whereas addition of two or more copies might be pathogenic. 

PMID- 26197981
TI  - Estimation of habitual iodine intake in Japanese adults using 16 d diet records
      over four seasons with a newly developed food composition database for iodine.
AB  - Although habitual seaweed consumption in Japan would suggest that iodine intake
      in Japanese is exceptionally high, intake data from diet records are limited. In
      the present study, we developed a composition database of iodine and estimated
      the habitual intake of iodine among Japanese adults. Missing values for iodine
      content in the existing composition table were imputed based on established
      criteria. 16 d diet records (4 d over four seasons) from adults (120 women aged
      30-69 years and 120 men aged 30-76 years) living in Japan were collected, and
      iodine intake was estimated. Habitual intake was estimated with the Best-power
      method. Totally, 995 food items were imputed. The distribution of iodine intake
      in 24 h was highly skewed, and approximately 55 % of 24 h values were < 300
      MUg/d. The median iodine intake in 24 h was 229 MUg/d for women and 273 MUg/d for
      men. All subjects consumed iodine-rich foods (kelp or soup stock) on one or more
      days of the sixteen survey days. The mean (median) habitual iodine intake was
      1414 (857) MUg/d for women and 1572 (1031) MUg/d for men. Older participants had
      higher intake than younger participants. The major contributors to iodine intake
      were kelp (60 %) and soup stock (30 %). Habitual iodine intake among Japanese was
      sufficient or higher than the tolerable upper intake level, particularly in older
      generations. The association between high iodine intake as that observed in the
      present study and thyroid disease requires further study.

PMID- 26197983
TI  - Opportunities and challenges of next-generation sequencing applications in
      ecological epigenetics.
AB  - Evolutionary theory posits that adaptation can result when populations harbour
      heritable phenotypic variation for traits that increase tolerance to local
      conditions. However, the actual mechanisms that underlie heritable phenotypic
      variation are not completely understood (Keller ). Recently, the potential role
      of epigenetic mechanisms in the process of adaptive evolution has been the
      subject of much debate (Pigliucci & Finkelman ). Studies of variation in DNA
      methylation in particular have shown that natural populations harbour high
      amounts of epigenetic variation, which can be inherited across generations and
      can cause heritable trait variation independently of genetic variation (Kilvitis
      et al. ). While we have made some progress addressing the importance of
      epigenetics in ecology and evolution using methylation-sensitive AFLP (MS-AFLP),
      this approach provides relatively few anonymous and dominant markers per
      individual. MS-AFLP are difficult to link to functional genomic elements or
      phenotype and are difficult to compare directly to genetic variation, which has
      limited the insights drawn from studies of epigenetic variation in natural
      nonmodel populations (Schrey et al. ). In this issue, Platt et al. provide an
      example of a promising approach to address this problem by applying a reduced
      representation bisulphite sequencing (RRBS) approach based on next-generation
      sequencing methods in an ecological context. 

PMID- 26197982
TI  - Neighborhood social capital is associated with participation in health checks of
      a general population: a multilevel analysis of a population-based lifestyle
      intervention- the Inter99 study.
AB  - BACKGROUND: Participation in population-based preventive health check has
      declined over the past decades. More research is needed to determine factors
      enhancing participation. The objective of this study was to examine the
      association between two measures of neighborhood level social capital on
      participation in the health check phase of a population-based lifestyle
      intervention. METHODS: The study population comprised 12,568 residents of 73
      Danish neighborhoods in the intervention group of a large population-based
      lifestyle intervention study - the Inter99. Two measures of social capital were
      applied; informal socializing and voting turnout. RESULTS: In a multilevel
      analysis only adjusting for age and sex, a higher level of neighborhood social
      capital was associated with higher probability of participating in the health
      check. Inclusion of both individual socioeconomic position and neighborhood
      deprivation in the model attenuated the coefficients for informal socializing,
      while voting turnout became non-significant. CONCLUSION: Higher level of
      neighborhood social capital was associated with higher probability of
      participating in the health check phase of a population-based lifestyle
      intervention. Most of the association between neighborhood social capital and
      participation in preventive health checks can be explained by differences in
      individual socioeconomic position and level of neighborhood deprivation.
      Nonetheless, there seems to be some residual association between social capital
      and health check participation, suggesting that activating social relations in
      the community may be an avenue for boosting participation rates in population
      based health checks. TRIAL REGISTRATION: ClinicalTrials.gov (registration no.
      NCT00289237 ).

PMID- 26197984
TI  - Radiographic and Computed Tomographic Configuration of Incomplete Proximal
      Fractures of the Proximal Phalanx in Horses Not Used for Racing.
AB  - OBJECTIVE: To characterize the configuration of incomplete proximal fractures of
      the proximal phalanx (P1) in horses not used for racing and compare radiographic
      with computed tomography (CT) findings. STUDY DESIGN: Historical cohort. ANIMALS:
      Twenty-four horses with incomplete fractures of P1. METHODS: Medical records of
      horses not used for racing diagnosed with an incomplete proximal fracture of P1
      based on clinical and radiographic examination and confirmed by CT between 2008
      and 2013 were retrieved. Radiographs and CT studies of these horses were analyzed
      using a subjective grading system and by measuring variables that characterized
      fracture configuration. RESULTS: Twenty-four horses were included (20 Warmbloods)
      with a mean age of 9.5 years and mean body weight of 574 kg. Fourteen forelimbs
      and 10 hind limbs were affected. Mean duration of lameness was 8.7 weeks.
      Computed tomography was superior to radiography in both identifying the fracture
      and determining fracture size and location. On CT, 92% of fractures were located
      in the mid-sagittal plane. Mean proximodistal length of the fracture was 13 mm.
      Fractures were frequently not bicortical. Fractures in forelimbs were located
      significantly more dorsally than fractures in hind limbs. A distinct fracture
      pattern with 2 subchondral lines running parallel in close proximity to each
      other was identified in 54% of cases. CONCLUSION: Incomplete proximal fractures
      of P1 have significant variation in their configurations, especially their
      dorsopalmar/-plantar location. Computed tomography examination allowed clear
      identification of the fracture configurations and was superior to radiography.

PMID- 26197985
TI  - A brief histone in time: understanding the combinatorial functions of histone
      PTMs in the nucleosome context.
AB  - It has been over 50 years since Allfrey et al. proposed that histone acetylation
      regulates RNA synthesis, and the study of histone modifications has progressed at
      an extraordinary pace for the past two decades. In this review, we provide a
      perspective on some key events and advances in our understanding of histone
      modifications. We also highlight reagents and tools from past to present that
      facilitated progress in this research field. Using histone H3 phosphorylation as
      an underlying thread, we review the rationale that led to the proposal of the
      histone code hypothesis, as well as examples that illustrate the concepts of
      combinatorial histone modifications and cross-talk pathways. We further highlight
      the importance of investigating these mechanisms in the context of nucleosomes
      rather than just at the histone level and present current and developing
      approaches for such studies. Overall, research on histone modifications has
      yielded great mechanistic insights into the regulation of genomic functions, and
      extending these studies using nucleosomes will further elucidate the complexity
      of these pathways in a more physiologically relevant context. 

PMID- 26197986
TI  - Boot-insole effects on comfort and plantar loading at the heel and fifth
      metatarsal during running and turning in soccer.
AB  - Plantar loading may influence comfort, performance and injury risk in soccer
      boots. This study investigated the effect of cleat configuration and insole
      cushioning levels on perception of comfort and in-shoe plantar pressures at the
      heel and fifth metatarsal head region. Nine soccer academy players (age 15.7 +/-
      1.6 years; height 1.80 +/- 0.40 m; body mass 71.9 +/- 6.1 kg) took part in the
      study. Two boot models (8 and 6 cleats) and two insoles (Poron and Poron/gel)
      provided four footwear combinations assessed using pressure insoles during
      running and 180 degrees  turning. Mechanical and comfort perception tests
      differentiated boot and insole conditions. During biomechanical testing, the
      Poron insole generally provided lower peak pressures than the Poron/gel insole,
      particularly during the braking step of the turn. The boot model did not
      independently influence peak pressures at the fifth metatarsal, and had minimal
      influence on heel loads. Specific boot-insole combinations performed differently
      (P < 0.05). The 8-cleat boot and the Poron insole performed best biomechanically
      and perceptually, but the combined condition did not. Inclusion of kinematic data
      and improved control of the turning technique are recommended to strengthen
      future research. The mechanical, perception and biomechanical results highlight
      the need for a multi-faceted approach in the assessment of footwear. 

PMID- 26197987
TI  - A planned admission protocol application in intensive care units.
AB  - BACKGROUND: The process of admission to an ICU may have a negative impact on a
      patient's physiological parameters and comfort. AIM: To determine the effect of
      providing a patient admission protocol on patients' comfort and physiological
      parameters prior to admission to the intensive care unit (ICU). DESIGN: A
      randomized, controlled experimental study. METHODS: This study included 100 (50
      control, 50 experimental) patients who experienced planned admissions to the ICU
      of a University Hospital. Standard forms were used to record patient information,
      evaluations and comfort. Data were collected from patients prior to, during and
      24 h after admission to the ICU and 24 h after being transferred. The
      experimental group was admitted to the ICU using the patient admission protocol
      and the control group underwent routine admittance. FINDINGS: There was no
      significant difference between the groups regarding the individual
      characteristics, physiology and comfort prior to, during or 24 h after admission
      to the ICU (p > 0.05). However, 24 h after being transferred, the experimental
      group's comfort was significantly higher than that of the control group (p <
      0.01). CONCLUSIONS: The use of the patient admission protocol does not affect the
      physiological parameters of patients; however, it does raise the comfort level of
      patients. RELEVANCE TO CLINICAL PRACTICE: The patient admission protocol specific
      to the institution (in this context, a unit introductory booklet) should be
      developed in ICUs. We suggest that admission to the ICU should be carried out in
      accordance with this protocol.

PMID- 26197989
TI  - Disseminated histoplasmosis partially mimicking a dermatomyositis in a patient
      with rheumatoid arthritis.
AB  - Histoplasma capsulatum var. capsulatum is a dimorphic fungus endemic to America
      and subtropical regions. Several cases of this opportunist mycosis have been
      reported in immunocompromised patients. We report the case of a patient treated
      with methotrexate and corticosteroid therapy for rheumatoid arthritis and who
      presented with disseminated histoplasmosis that partially mimicked a
      dermatomyositis. 

PMID- 26197988
TI  - Role of membrane Hsp70 in radiation sensitivity of tumor cells.
AB  - BACKGROUND: The major stress-inducible heat shock protein 70 (Hsp70) is
      frequently overexpressed in the cytosol and integrated in the plasma membrane of
      tumor cells via lipid anchorage. Following stress such as non-lethal irradiation
      Hsp70 synthesis is up-regulated. Intracellular located Hsp70 is known to exert
      cytoprotective properties, however, less is known about membrane (m)Hsp70.
      Herein, we investigate the role of mHsp70 in the sensitivity towards irradiation
      in tumor sublines that differ in their cytosolic and/or mHsp70 levels. METHODS:
      The isogenic human colon carcinoma sublines CX(+) with stable high and CX(-) with
      stable low expression of mHsp70 were generated by fluorescence activated cell
      sorting, the mouse mammary carcinoma sublines 4 T1 (4 T1 ctrl) and Hsp70 knock
      down (4 T1 Hsp70 KD) were produced using the CRISPR/Cas9 system, and the Hsp70
      down-regulation in human lung carcinoma sublines H1339 ctrl/H1339 HSF-1 KD and
      EPLC-272H ctrl/EPLC-272H HSF-1 KD was achieved by small interfering (si)RNA
      against Heat shock factor 1 (HSF-1). Cytosolic and mHsp70 was quantified by
      Western blot analysis/ELISA and flow cytometry; double strand breaks (DSBs) and
      apoptosis were measured by flow cytometry using antibodies against gammaH2AX and
      real-time PCR (RT-PCR) using primers and antibodies directed against apoptosis
      related genes; and radiation sensitivity was determined using clonogenic cell
      surviving assays. RESULTS: CX(+)/CX(-) tumor cells exhibited similar cytosolic
      but differed significantly in their mHsp70 levels, 4 T1 ctrl/4 T1 Hsp70 KD cells
      showed significant differences in their cytosolic and mHsp70 levels and H1339
      ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/EPLC-272H HSF-1 KD lung carcinoma cell
      sublines had similar mHsp70 but significantly different cytosolic Hsp70 levels.
      gammaH2AX was significantly up-regulated in irradiated CX(-) and 4 T1 Hsp70 KD
      with low basal mHsp70 levels, but not in their mHsp70 high expressing
      counterparts, irrespectively of their cytosolic Hsp70 content. After irradiation
      gammaH2AX, Caspase 3/7 and Annexin V were up-regulated in the lung carcinoma
      sublines, but no significant differences were observed in H1339 ctrl/H1339 HSF-1
      KD, and EPLC-272H ctrl/EPLC-272H HSF-1 KD that exhibit identical mHsp70 but
      different cytosolic Hsp70 levels. Clonogenic cell survival was significantly
      lower in CX(-) and 4 T1 Hsp70 KD cells with low mHsp70 expression, than in CX+
      and 4 T1 ctrl cells, whereas no difference in clonogenic cell survival was
      observed in H1339 ctrl/H1339 HSF-1 KD and EPLC-272H ctrl/ EPLC-272H HSF-1 KD
      sublines with identical mHsp70 but different cytosolic Hsp70 levels. CONCLUSION:
      In summary, our results indicate that mHsp70 has an impact on radiation
      resistance.

PMID- 26197990
TI  - Predict esophageal varices via routine trans-abdominal ultrasound: A design of
      classification analysis model.
AB  - BACKGROUND AND AIMS: Upper gastrointestinal endoscopy remains the gold standard
      for diagnosis of esophageal varices. Trans-abdominal ultrasound, as a noninvasive
      routine examination for the follow-up of cirrhosis patient, is safe, cheap, easy
      to perform, and plays an important role. In this study, we attempt to design a
      practical classification analysis model to predict esophageal varices via
      ultrasound. METHODS: Compared with endoscopy, the ultrasound qualitative signs
      (lower esophageal Doppler signals, left gastric vein hepatofugal flow, and
      paraumbilical vein recanalization) and quantitative parameters (spleen diameter,
      spleen vein diameter, portal vein diameter, and portal vein velocity) have been
      evaluated in 286 cirrhosis patients. RESULTS: The classification analysis model
      is designed as that: the patients are defined with esophageal varices high risk,
      who with any ultrasound qualitative signs or who with spleen diameter greater
      than 162 mm without qualitative parameters. The sensitivity for detecting
      esophageal varices is 97.5% and the specificity is 82.6%, while the positive
      predictive value is 96.7%, negative predictive value is 83.4%, and the omission
      diagnostic rate is 2.5%. CONCLUSIONS: This classification analysis model design
      includes ultrasound qualitative signs and spleen diameter, which can be detected
      easily via routine ultrasound without other auxiliary. The classification
      analysis model is useful in detecting esophageal varices, which may be a
      supplement for predicting of esophageal varices, and reducing the frequency of
      endoscopy in the follow-up of cirrhosis patients.

PMID- 26197991
TI  - Birth Options after Having a Cesarean.

PMID- 26197992
TI  - Synthesis of 3-heteroarylchromones via a photochemical reaction.
AB  - The direct coupling of 3-iodochromen-4-ones with heteroaromatics has been
      achieved via a photochemical reaction. A variety of 3-heteroarylchromones was
      obtained in moderate to good yields from the corresponding 3-iodochromen-4-ones
      and heteroaromatics, such as pyrrole, furan, thiophene, and benzofuran. The
      reaction worked smoothly in acetonitrile under a mercury lamp without any
      additives, providing a catalyst- and base-free approach for the synthesis of 3
      heteroarylchromones. 

PMID- 26197993
TI  - Escherichia coli O157 Outbreaks in the United States, 2003-2012.

PMID- 26197994
TI  - Identification of a new HLA-B*27 allele, B*27:133, in a Russian individual.
AB  - The sequence of HLA-B*27:133 differs from HLA-B*27:05:02 by one nucleotide change
      within exon 3. 

PMID- 26197997
TI  - Theoretical and experimental studies on the atmospheric degradation of 2-bromo
      3,3,3-trifluoropropene.
AB  - As a new kind of Halon replacement, 2-bromo-3,3,3-trifluoropropene (2-BTP) is
      finding application as a fire extinguishing agent in confined spaces. For
      assessing its environmental impact, it is necessary to perform kinetic and
      product studies of its degradation in the atmospheric environment. In this sense,
      five possible reaction pathways between 2-BTP and OH radicals are found by
      Gaussian 03. Detailed analysis shows that the main product is the CF3CBrCH2OH
      radical, which may produce a series of compounds by further reaction with O2, NO,
      etc. In order to further prove the validity of the theoretical calculations and
      investigate the atmospheric transformation process of 2-BTP, atmospheric
      degradation of 2-BTP is then studied experimentally under controlled radiation
      conditions. Based on the theoretical analyses and experimental results, the
      atmospheric degradation mechanism of 2-BTP is finally proposed and detailed
      information on the atmospheric chemistry of 2-BTP is provided. 

PMID- 26197995
TI  - Effects of aging in the expression of NOD-like receptors and inflammasome-related
      genes in oral mucosa.
AB  - The molecular changes underlying the higher risk of chronic inflammatory
      disorders during aging remain incompletely understood. Molecular variations in
      the innate immune response related to recognition and interaction with microbes
      at mucosal surfaces could be involved in aging-related inflammation. We developed
      an ontology analysis of 20 nucleotide-binding and oligomerization domain (NOD)
      like receptors (NLRs) and seven inflammasome-related genes (IRGs) in healthy and
      inflamed/periodontitis oral mucosal tissues from young, adolescent, adult, and
      aged non-human primates (Macaca mulatta) using the GeneChip((r)) Rhesus Macaque
      Genome array. Validation of some of the significant changes was done by
      quantitative reverse transcription-polymerase chain reaction. The expression of
      NLRB/NAIP, NLRP12, and AIM2 increased with aging in healthy mucosa whereas
      NLRC2/NOD2 expression decreased. Although higher expression levels of some NLRs
      were generally observed with periodontitis in adult mucosal tissues (e.g.
      NLRB/NAIP, NLRP5, and NLRX1), various receptors (e.g. NLRC2/NOD2 and NLRP2) and
      the inflammasome adaptor protein ASC, exhibited a significant reduction in
      expression in aged periodontitis tissues. Accordingly, the expression of NLR
      activated innate immune genes, such as HBD3 and IFNB1, was impaired in aged but
      not adult periodontitis tissues. Both adult and aged tissues showed significant
      increase in interleukin-1beta expression. These findings suggest that the
      expression of a subset of NLRs appears to change with aging in healthy oral
      mucosa, and that aging-related oral mucosal inflammation could involve an
      impaired regulation of the inflammatory and antimicrobial response associated
      with downregulation of specific NLRs and IRGs. 

PMID- 26197998
TI  - Body size distributions of the pale grass blue butterfly in Japan: Size rules and
      the status of the Fukushima population.
AB  - The body size of the pale grass blue butterfly, Zizeeria maha, has been used as
      an environmental indicator of radioactive pollution caused by the Fukushima
      nuclear accident. However, geographical and temporal size distributions in Japan
      and temperature effects on size have not been established in this species. Here,
      we examined the geographical, temporal, and temperature-dependent changes of the
      forewing size of Z. maha argia in Japan. Butterflies collected in 2012 and 2013
      from multiple prefectures throughout Japan demonstrated an inverse relationship
      of latitude and forewing size, which is the reverse of Bergmann's cline. The
      Fukushima population was significantly larger than the Aomori and Miyagi
      populations and exhibited no difference from most of the other prefectural
      populations. When monitored at a single geographic locality every other month,
      forewing sizes were the largest in April and the smallest in August. Rearing
      larvae at a constant temperature demonstrated that forewing size followed the
      temperature-size rule. Therefore, the converse Bergmann's rule and the
      temperature-size rule coexist in this multivoltine species. Our study establishes
      this species as a useful environmental indicator and supports the idea that the
      size reduction observed only in Fukushima Prefecture in 2011 was caused by the
      environmental stress of radioactive pollution. 

PMID- 26197999
TI  - Specific inhibition of bile acid transport alters plasma lipids and GLP-1.
AB  - BACKGROUND: Elobixibat is a minimally absorbed ileal bile acid (BA) transporter
      (IBAT) inhibitor in development against chronic constipation (CC) and
      constipation-predominant Irritable Bowel Syndrome (IBS-C). CC is associated with
      an increased risk for cardiovascular disease and type2 diabetes mellitus. The
      objectives of this study were to evaluate metabolic effects of elobixibat.
      Effects on plasma lipids and BA synthesis were evaluated utilizing a 4-week,
      placebo-controlled study in patients with dyslipidemia while changes of glucagon
      like peptide-1 (GLP-1) by elobixibat was assayed in samples from a 14 day high
      dose elobixibat study in patients with CC. METHODS: Thirty-six dyslipidemic
      patients, 21 females, mean age 63 years, were randomized to 2.5 mg or 5 mg
      elobixibat or placebo once daily for four weeks. The primary endpoint was the
      change in low density lipoprotein (LDL) cholesterol. Secondary endpoints included
      other lipid parameters and serum 7alpha-hydroxy-4-cholesten-3-one (C4), a marker
      of BA (bile acid) synthesis. Another study, in 36 patients with CC treated with
      high dose elobixibat; 15 mg or 20 mg/day or placebo for 14 days, was evaluated
      for changes in GLP-1. RESULTS: In the dyslipidemia study LDL cholesterol was
      reduced by 7.4 % (p = 0.044), and the LDL/HDL ratio was decreased by 18 % (p =
      0.004). Serum C4 increased, indicating that BA synthesis was induced. No serious
      adverse events were recorded. In the CC study, GLP-1 increased significantly in
      both the 15 mg (20.7 +/- 2.4 pmol/L; p = 0.03) and the 20 mg group (25.6 +/- 4.9
      pmol/L; p = 0.02). CONCLUSIONS: Elobixibat reduces LDL cholesterol and LDL/HDL
      ratio and increase circulating peak GLP-1 levels, the latter in line with
      increased intestinal BA mediated responses in humans. TRIAL REGISTRATIONS:
      ClinicalTrial.gov: NCT01069783 and NCT01038687 .

PMID- 26198000
TI  - Monitoring therapeutic efficacy of sunitinib using [(18)F]FDG and [(18)F]FMISO
      PET in an immunocompetent model of luminal B (HER2-positive)-type mammary
      carcinoma.
AB  - BACKGROUND: Clinical studies implying the sunitinib multi-kinase inhibitor have
      led to disappointing results for breast cancer care but mostly focused on HER2
      negative subtypes. Preclinical researches involving this drug mostly concern
      Triple Negative Breast Cancer (TNBC) murine models. Here, we explored the
      therapeutic efficacy of sunitinib on a PyMT-derived transplanted model classified
      as luminal B (HER2-positive) and monitored the response to treatment using both
      in vivo and ex vivo approaches. METHODS: Tumour-induced animals were treated for
      9 (n = 7) or 14 (n = 8) days with sunitinib at 40 mg/kg or with vehicle only.
      Response to therapy was assessed in vivo by monitoring glucose tumour metabolism
      and hypoxia using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and
      [(18)F]fluoromisonidazole ([(18)F]FMISO) Positron Emission Tomography (PET).
      After primary tumour excision, ex vivo digital microscopy was performed on
      treated and control samples to estimate vascular density (CD31), apoptosis
      (Tunel), proliferation (Ki-67), Tumour-Associated Macrophage (TAM) infiltration
      (F4/80), metabolism (GLUT1) and cellular response to hypoxia (HIF1 alpha). The
      drug impact on the metastasis rate was evaluated by monitoring the PyMT gene
      expression in the lungs of the treated and control groups. RESULTS: Concomitant
      with sunitinib-induced tumour size regression, [(18)F]FDG PET imaging showed a
      stable glycolysis-related metabolism inside tumours undergoing treatment compared
      to an increased metabolism in untreated tumours, resulting at treatment end in
      1.5 less [(18)F]FDG uptake in treated (n = 4) vs control (n = 3) tumours (p <
      0.05). With this small sample, [(18)F]FMISO PET showed a non-significant decrease
      of hypoxia in treated vs control tumours. The drug triggered a 4.9 fold vascular
      volume regression (p < 0.05), as well as a 17.7 fold induction of tumour cell
      apoptosis (p < 0.001). The hypoxia induced factor 1 alpha (HIF1 alpha) expression
      was twice lower in the treated group than in the control group (p < 0.05).
      Moreover, the occurrence of lung metastases was not reduced by the drug.
      CONCLUSIONS: [(18)F]FDG and [(18)F]FMISO PET were relevant approaches to study
      the response to sunitinib in this luminal B (HER2-positive) model. The sunitinib
      induced vascular network shrinkage did not significantly increase tumour hypoxia,
      suggesting that tumour regression was mainly due to the pro-apoptotic properties
      of the drug. Sunitinib did not inhibit the metastatic process in this PyMT
      transplanted model.

PMID- 26198001
TI  - Poised chromatin and bivalent domains facilitate the mitosis-to-meiosis
      transition in the male germline.
AB  - BACKGROUND: The male germline transcriptome changes dramatically during the
      mitosis-to-meiosis transition to activate late spermatogenesis genes and to
      transiently suppress genes commonly expressed in somatic lineages and
      spermatogenesis progenitor cells, termed somatic/progenitor genes. RESULTS: These
      changes reflect epigenetic regulation. Induction of late spermatogenesis genes
      during spermatogenesis is facilitated by poised chromatin established in the stem
      cell phases of spermatogonia, whereas silencing of somatic/progenitor genes
      during meiosis and postmeiosis is associated with formation of bivalent domains
      which also allows the recovery of the somatic/progenitor program after
      fertilization. Importantly, during spermatogenesis mechanisms of epigenetic
      regulation on sex chromosomes are different from autosomes: X-linked
      somatic/progenitor genes are suppressed by meiotic sex chromosome inactivation
      without deposition of H3K27me3. CONCLUSIONS: Our results suggest that bivalent
      H3K27me3 and H3K4me2/3 domains are not limited to developmental promoters (which
      maintain bivalent domains that are silent throughout the reproductive cycle), but
      also underlie reversible silencing of somatic/progenitor genes during the mitosis
      to-meiosis transition in late spermatogenesis.

PMID- 26198002
TI  - Global patterns and drivers of phylogenetic structure in island floras.
AB  - Islands are ideal for investigating processes that shape species assemblages
      because they are isolated and have discrete boundaries. Quantifying phylogenetic
      assemblage structure allows inferences about these processes, in particular
      dispersal, environmental filtering and in-situ speciation. Here, we link
      phylogenetic assemblage structure to island characteristics across 393 islands
      worldwide and 37,041 vascular plant species (representing angiosperms overall,
      palms and ferns). Physical and bioclimatic factors, especially those impeding
      colonization and promoting speciation, explained more variation in phylogenetic
      structure of angiosperms overall (49%) and palms (52%) than of ferns (18%). The
      relationships showed different or contrasting trends among these major plant
      groups, consistent with their dispersal- and speciation-related traits and
      climatic adaptations. Phylogenetic diversity was negatively related to isolation
      for palms, but unexpectedly it was positively related to isolation for
      angiosperms overall. This indicates strong dispersal filtering for the
      predominantly large-seeded, animal-dispersed palm family whereas colonization
      from biogeographically distinct source pools on remote islands likely drives the
      phylogenetic structure of angiosperm floras. We show that signatures of dispersal
      limitation, environmental filtering and in-situ speciation differ markedly among
      taxonomic groups on islands, which sheds light on the origin of insular plant
      diversity. 

PMID- 26198003
TI  - Modulating protein activity using tethered ligands with mutually exclusive
      binding sites.
AB  - The possibility to design proteins whose activities can be switched on and off by
      unrelated effector molecules would enable applications in various research areas,
      ranging from biosensing to synthetic biology. We describe here a general method
      to modulate the activity of a protein in response to the concentration of a
      specific effector. The approach is based on synthetic ligands that possess two
      mutually exclusive binding sites, one for the protein of interest and one for the
      effector. Tethering such a ligand to the protein of interest results in an
      intramolecular ligand-protein interaction that can be disrupted through the
      presence of the effector. Specifically, we introduce a luciferase controlled by
      another protein, a human carbonic anhydrase whose activity can be controlled by
      proteins or small molecules in vitro and on living cells, and novel fluorescent
      and bioluminescent biosensors. 

PMID- 26198004
TI  - Multilocus microsatellite typing of Leishmania infantum isolates in monitored
      Leishmania/HIV coinfected patients.
AB  - BACKGROUND: Leishmania infantum is the main etiological agent of both visceral
      and cutaneous clinical forms of leishmaniasis in the Mediterranean area.
      Leishmania/HIV coinfection in this area is characterized by a chronic course and
      frequent recurrences of clinical episodes. The present study using Multilocus
      Microsatellite Typing (MLMT) analysis, a highly discriminative tool, aimed to
      genetically characterize L. infantum isolates taken from monitored Leishmania/HIV
      coinfected patients presenting successive clinical episodes. METHODS: In this
      study, by the analysis of 20 microsatellite loci, we studied the MLMT profiles of
      25 L. infantum isolates from 8 Leishmania/HIV coinfected patients who had
      experienced several clinical episodes. Two to seven isolates per patient were
      taken before and after treatment, during clinical and non-clinical episodes, with
      time intervals of 6 days to 29 months. Genetic diversity, clustering and phenetic
      analyses were performed. RESULTS: MLMT enabled us to study the genetic
      characteristics of the 25 L. infantum isolates, differentiating 18 genotypes,
      corresponding to a genotypic diversity of 0.72. Fifteen genotypes were unique in
      the total sample set and only 3 were repeated, 2 of which were detected in
      different patients. Both clustering and phylogenetic analyses provided insights
      into the genetic links between the isolates; in five patients isolates showed
      clear genetic links: either the genotype was exactly the same or only slightly
      different. In contrast, the isolates of the other three patients were dispersed
      in different clusters and some could be the result of mixing between populations.
      CONCLUSIONS: Our data indicated a great MLMT variability between isolates from
      coinfected patients and no predominant genotype was observed. Despite this,
      almost all clinical episodes could be interpreted as a relapse rather than a
      reinfection. The results showed that diverse factors like an intrapatient
      evolution over time or culture bias could influence the parasite population
      detected in the patient, making it difficult to differentiate between relapse and
      reinfection.

PMID- 26198005
TI  - Characterization of a Pyrazolo[4,3-d]pyrimidine Inhibitor of Cyclin-Dependent
      Kinases 2 and 5 and Aurora A With Pro-Apoptotic and Anti-Angiogenic Activity In
      Vitro.
AB  - Selective inhibitors of kinases that regulate the cell cycle, such as cyclin
      dependent kinases (CDKs) and aurora kinases, could potentially become powerful
      tools for the treatment of cancer. We prepared and studied a series of 3,5,7
      trisubstituted pyrazolo[4,3-d]pyrimidines, a new CDK inhibitor scaffold, to
      assess their CDK2 inhibitory and antiproliferative activities. A new compound,
      2i, which preferentially inhibits CDK2, CDK5, and aurora A was identified. Both
      biochemical and cellular assays indicated that treatment with compound 2i caused
      the downregulation of cyclins A and B, the dephosphorylation of histone H3 at
      Ser10, and the induction of mitochondrial apoptosis in the HCT-116 colon cancer
      cell line. It also reduced migration as well as tube and lamellipodia formation
      in human endothelial cells. The kinase inhibitory profile of compound 2i suggests
      that its anti-angiogenic activity is linked to CDK5 inhibition. This dual mode of
      action involving apoptosis induction in cancer cells and the blocking of
      angiogenesis-like activity in endothelial cells offers possible therapeutic
      potential. 

PMID- 26198006
TI  - Cultural differences in ant-dipping tool length between neighbouring chimpanzee
      communities at Kalinzu, Uganda.
AB  - Cultural variation has been identified in a growing number of animal species
      ranging from primates to cetaceans. The principal method used to establish the
      presence of culture in wild populations is the method of exclusion. This method
      is problematic, since it cannot rule out the influence of genetics and ecology in
      geographically distant populations. A new approach to the study of culture
      compares neighbouring groups belonging to the same population. We applied this
      new approach by comparing ant-dipping tool length between two neighbouring
      communities of chimpanzees (Pan troglodytes schweinfurthii) in the Kalinzu
      Forest, Uganda. Ant-dipping tool length varies across chimpanzee study sites in
      relation to army ant species (Dorylus spp.) and dipping location (nest vs.
      trail). We compared the availability of army ant species and dipping tool length
      between the two communities. M-group tools were significantly longer than S-group
      tools, despite identical army ant target species availabilities. Moreover, tool
      length in S-group was shorter than at all other sites where chimpanzees prey on
      epigaeic ants at nests. Considering the lack of ecological differences between
      the two communities, the tool length difference appears to be cultural. Our
      findings highlight how cultural knowledge can generate small-scale cultural
      diversification in neighbouring chimpanzee communities. 

PMID- 26198007
TI  - Association between pelvic floor muscle trauma and pelvic organ prolapse 20 years
      after delivery.
AB  - INTRODUCTION AND HYPOTHESIS: It is known that pelvic floor muscle trauma (PFMT)
      after vaginal delivery is associated with pelvic organ prolapse (POP) symptoms
      (sPOP) and signs (POP-Q >=2) in patient populations. Our aims were to establish
      the prevalence and investigate a possible association between PFMT and sPOP and
      POP-Q >=2 in healthy women 20 years after their first delivery. METHODS: During
      2013 and 2014 we conducted a cross-sectional study among 847 women who delivered
      their first child between 1990 and 1997. Women responded to a postal
      questionnaire and were offered a clinical examination including prolapse grading
      and pelvic floor ultrasonography. The main outcome measures were sPOP, POP-Q >=2
      and PFMT, defined by levator avulsion or a levator hiatal area on Valsalva
      manoeuvre of >40 cm(2) on ultrasonography. RESULTS: Of the 847 eligible women,
      608 (72 %) were examined. Data on POP symptoms, POP-Q stage, levator avulsion and
      levator hiatal area were available in 598, 608, 606 and 554 women, respectively,
      and of these 75 (13%) had sPOP, 275 (45%) had POP-Q >=2, 113 (19 %) had levator
      avulsion and 164 (30%) had a levator hiatal area >40 cm(2). Levator avulsion was
      associated with POP-Q >=2 with an odds ratio (OR) of 9.91 and a 95% confidence
      interval (CI) of 5.73 - 17.13, and with sPOP (OR 2.28, 95% CI 1.34 - 3.91).
      Levator hiatal area >40 cm(2) was associated with POP-Q >=2 (OR 6.98, 95% CI
      4.54, - 10.74) and sPOP (OR 3.28, 95 % CI 1.96 - 5.50). CONCLUSION: Many healthy
      women selected from the general population have symptoms and signs of POP 20
      years after their first delivery, and PFMT is associated with POP-Q >=2 and sPOP.

PMID- 26198008
TI  - Erratum to: The introduction of mid-urethral slings: an evaluation of literature.

PMID- 26198011
TI  - Diabetes Mellitus Impairs Left Ventricular Mass Regression after Surgical or
      Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis.
AB  - BACKGROUND: It is well-documented that persistent myocardial hypertrophy in
      patients with aortic stenosis is related to suboptimal postoperative outcomes
      after aortic valve replacement. Although diabetes is known to potentially
      exacerbate myocardial hypertrophy, it has yet to be examined if it affects
      postoperative left ventricular mass regression (LVMR). METHODS: A single-centre,
      retrospective analysis was performed on 183 consecutive patients who underwent
      either surgical or transcatheter aortic valve replacement between 2010 and May
      2013. Patient demographics, postoperative outcomes and echocardiographic data
      were obtained preoperatively and a year after surgery. RESULTS: There were 42
      diabetic and 141 non-diabetic patients. Preoperative characteristics of diabetic
      patients were statistically similar to those of non-diabetic patients, except for
      higher prevalence of hyperlipidaemia (p <0.001) and history of cerebrovascular
      disorder (p=0.046) in diabetic patients. Median value of postoperative LVMR of
      all patients was -36.5 g/m(2), and was significantly greater in the non-diabetics
      compared to the diabetics (-39.1 vs. -22.2 g/m(2), p=0.008). Univariate and
      multivariate analyses were performed on preoperative variables, and stepwise
      multiple regression analysis demonstrated that diabetes (standardised partial
      regression coefficient (SPRC)=-0.187, p=0.018), female gender (SPRC=0.245,
      p=0.026) and age (SPRC=0.203, p=0.018) were associated with poor postoperative
      LVMR. CONCLUSIONS: Patients with diabetes showed suboptimal postoperative LVMR,
      and the disease was a prognostic factor that was associated with poor LVMR. These
      findings suggest that diabetes may predispose the particular group of patients to
      worse postoperative outcomes.

PMID- 26198010
TI  - Investigation of depression, anxiety and quality of life in patients with knee
      osteoarthritis: a comparative study.
AB  - INTRODUCTION: Osteoarthritis (OA) affects the articular cartilage and subchondral
      bone, compromising the joint as a whole. The knee joint is characterized as one
      of the main sites of involvement of OA and the most significant risk factors for
      developing the disease are aging, overweight and female gender. OA is considered
      one of the most frequent causes of disability, which may affect the quality of
      life of the patients, favoring the onset of mental disorders. OBJECTIVE: To
      investigate whether anxiety and depression symptoms are more significant in women
      with OA, when compared with women without this diagnosis, and to what extent this
      rheumatic disease affects the quality of life of these patients. METHODS: The
      study included 75 women, mean age 67 years; 40 were diagnosed with knee OA and 35
      without this diagnosis. The following instruments were used: State-Trait Anxiety
      Inventory (STAI), Beck Depression Inventory (BDI) and SF-36, a quality of life
      questionnaire. RESULTS: Women with knee OA have higher rates of depression and
      anxiety when compared to controls; in addition, they have a lower quality of
      life. CONCLUSION: We believe that the treatment of patients with OA should
      consider the combination of pharmacotherapy, psychotherapy, counseling and family
      support, in order to achieve a better quality of life.

PMID- 26198012
TI  - Health care costs and work absenteeism in smokers: study in an urban community.
AB  - INTRODUCTION: Higher morbidity caused by smoking-related diseases could increase
      health costs. We analyzed differences in the use of healthcare resources,
      healthcare costs and days of work absenteeism among smokers and non-smokers.
      METHODS: Cross-sectional study in smokers and non-smokers, aged between 45 and 74
      years, from one urban health area. The variables studied were: age, sex, alcohol
      intake, physical activity, obesity, diseases, attendance at primary care clinics
      and hospital emergency rooms, days of hospitalization, prescription drug
      consumption and work absenteeism (in days). Annual cost according to the unit
      cost of each service (direct costs), and indirect costs according to the number
      of days missed from work was calculated. Crude and adjusted risks were calculated
      using logistic regression. RESULTS: Five hundred patients were included: 50% were
      smokers, 74% (372) men and 26% (128) women. Smokers used more healthcare
      resources, consumed more prescription drugs and had more days off work than non
      smokers. Respective direct and indirect costs in smokers were 848.64 euros (IQ 25
      75: 332.65-1517.10) and 2253.90 euros (IQ 25-75: 1024.50-13113.60), and in non
      smokers were 474.71 euros (IQ 25-75: 172.88-979.59) and 1434.30 euros (IQ 25-75:
      614.70-4712.70). The likelihood of generating high healthcare costs was more than
      double for smokers (OR=2.14; 95% CI: 1.44-3.19). CONCLUSION: More investment in
      programs for the prevention and treatment of smoking, as a health policy
      priority, could help to reduce the health and social costs of smoking.

PMID- 26198013
TI  - Interactions between the trianionic ligand-centred redox-active metalloligand
      [Cr(III)(perfluorocatecholato)3](3-) and guest metal ions.
AB  - The redox-active metalloligand (RML) (Et3NH)3[Cr(III)(F4Cat)3] (F4Cat =
      perfluorocatecholato) () was synthesized and its interactions with guest metal
      ions Li(+), Mn(2+), Fe(2+), Co(2+), Cu(2+), and Zn(2+) were examined. Cyclic
      voltammetry measurements and spectroelectrochemical studies revealed that complex
      shows three-step ligand-centred one-electron oxidation to consecutively generate
      [Cr(III)(F4Cat)2(F4SQ)](2-) (F4SQ = perfluorosemiquinonato),
      [Cr(III)(F4Cat)(F4SQ)2](-), and [Cr(III)(F4SQ)3] at -0.12, 0.23, and 0.53 V vs.
      Ag/Ag(+) in dichloromethane, or at -0.21, 0.08, and 0.50 V in acetonitrile
      (MeCN), respectively. Titration experiments in MeCN revealed that treatment of
      with Cu(2+) leads to the formation of [Cr(III)(F4Cat)2(F4SQ)](2-) and Cu(+)via a
      redox reaction. However, when was treated with Li(+), Mn(2+), Fe(2+), Co(2+), and
      Zn(2+), further titration experiments revealed that these metal ions coordinated
      via the lone pairs on the coordinating oxygen atoms of the F4Cat(2-) moieties in
      a one-to-one ratio, and binding constants of 3.7 (+/-0.3) * 10(4) (Li(+)), 1.5
      (+/-0.2) * 10(5) (Mn(2+)), 2.2 (+/-0.4) * 10(5) (Fe(2+)), 1.9 (+/-0.2) * 10(5)
      (Co(2+)), and 3.8 (+/-0.4) * 10(5) M(-1) (Zn(2+)) were established. Moreover, the
      oxidation potentials of were positively shifted by 0.08-0.33 V upon addition of
      guest metal ions. Spectroelectrochemical studies of in the presence of guest
      metal ions suggested that ligand-centred one- and two-electron oxidation of the
      RML occurred for Li(+), Mn(2+), Co(2+), and Zn(2+), respectively, while guest
      metal-centred one-electron oxidation was observed for Fe(2+). Considering all the
      aforementioned results, this study demonstrated for the first time the ability of
      [Cr(III)(F4Cat)3](3-) to act as a RML in solution. 

PMID- 26198014
TI  - Thermodynamics, interfacial pressure isotherms and dilational rheology of mixed
      protein-surfactant adsorption layers.
AB  - Proteins and their mixtures with surfactants are widely used in many
      applications. The knowledge of their solution bulk behavior and its impact on the
      properties of interfacial layers made great progress in the recent years.
      Different mechanisms apply to the formation process of protein/surfactant
      complexes for ionic and non-ionic surfactants, which are governed mainly by
      electrostatic and hydrophobic interactions. The surface activity of these
      complexes is often remarkably different from that of the individual protein and
      has to be considered in respective theoretical models. At very low protein
      concentration, small amounts of added surfactants can change the surface activity
      of proteins remarkably, even though no strongly interfacial active complexes are
      observed. Also small added amounts of non-ionic surfactants change the surface
      activity of proteins in the range of small bulk concentrations or surface
      coverages. The modeling of the equilibrium adsorption behavior of proteins and
      their mixtures with surfactants has reached a rather high level. These models are
      suitable also to describe the high frequency limits of the dilational
      viscoelasticity of the interfacial layers. Depending on the nature of the
      protein/surfactant interactions and the changes in the interfacial layer
      composition rather complex dilational viscoelasticities can be observed and
      described by the available models. The differences in the interfacial behavior,
      often observed in literature for studies using different experimental methods,
      are at least partially explained by a depletion of proteins, surfactants and
      their complexes in the range of low concentrations. A correction of these
      depletion effects typically provides good agreement between the data obtained
      with different methods, such as drop and bubble profile tensiometry. 

PMID- 26198015
TI  - Safety and Efficacy of Selective Neurectomy of the Gastrocnemius Muscle for Calf
      Reduction in 300 Cases.
AB  - BACKGROUND: Liposuction alone is not always sufficient to correct the shape of
      the lower leg, and muscle reduction may be necessary. OBJECTIVE: To assess the
      outcomes of a new technique of selective neurectomy of the gastrocnemius muscle
      to correct calf hypertrophy. METHODS: Between October 2007 and May 2010, 300
      patients underwent neurectomy of the medial and lateral heads of the
      gastrocnemius muscle at the Department of Cosmetic and Plastic Surgery, the
      Second People's Hospital of Guangdong Province (Guangzhou, China) to correct the
      shape of their lower legs. Follow-up data from these 300 patients were analyzed
      retrospectively. Cosmetic results were evaluated independently by the surgeon,
      the patient, and a third party. Preoperative and postoperative calf
      circumferences were compared. The Fugl-Meyer motor function assessment was
      evaluated 3 months after surgery. RESULTS: The average reduction in calf
      circumference was 3.2 +/- 1.2 cm. The Fugl-Meyer scores were normal in all
      patients both before and 3 months after surgery. A normal calf shape was achieved
      in all patients. Six patients complained of fatigue while walking and four of
      scar pigmentation, but in all cases, this resolved within 6 months. Calf
      asymmetry was observed in only two patients. CONCLUSION: The present series
      suggests that neurectomy of the medial and lateral heads of the gastrocnemius
      muscle may be safe and effective for correcting the shape of the calves. 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- 26198016
TI  - Results of Ahmed glaucoma valve implantation in primary congenital glaucoma.

PMID- 26198017
TI  - Evolution of focal choroidal excavation underlying combined hamartoma of the
      retina and retinal pigment epithelium in a child.
AB  - Combined hamartoma of the retina and retinal pigment epithelium (RPE) is a benign
      tumor seen mostly in children. Enhanced-depth imaging optical coherence
      tomography (OCT) of these tumors often shows an epiretinal membrane, tangential
      traction, disorganization of the retinal layers, and underlying uniform choroidal
      thinning. We describe the evolution over 9 years of focal choroidal excavation, a
      novel finding on OCT characterized as a "microstaphyloma," in a girl with
      combined hamartoma of the retina and RPE. 

PMID- 26198018
TI  - Feasibility of a reduction protocol in the emergency department for diaphyseal
      forearm fractures in children.
AB  - INTRODUCTION: Diaphyseal forearm fractures are very common pediatric traumas. At
      present, distal radius metaphyseal fractures are often successfully treated with
      closed reduction by emergency physicians. However, the management of diaphyseal
      fractures remains controversial. The purpose of this study was to analyze the
      results of diaphyseal forearm fractures in the emergency department (ED) in
      children. MATERIALS AND METHODS: In a prospective 2-year-study, all closed
      diaphyseal forearm fractures in patients under 15, with an angle of >15 degrees 
      and treated by closed reduction in the ED were included. Fractures with
      overlapping fragments were excluded. Reduction was performed by an emergency
      physician, with a standardized analgesic protocol (painkillers and nitrous
      oxide). Clinical tolerance was checked within the first 24hours, and the
      radiographic stability of reduction was assessed at days 8 and 15. Initial and
      final follow-up radiographs were analyzed. Elbow and wrist range of motion was
      assessed at the final follow-up. RESULTS: Sixty patients (41 boys and 19 girls)
      were included. Mean age was 5.2 years old (+/-3). At initial evaluation, the
      maximum angle was 30 degrees  (+/-11.3). After reduction, the maximum angle was
      significantly reduced (30 degrees  vs. 5 degrees , P<0.001). Mean immobilization
      in a cast was 11.7 weeks (+/-2). There were no cast related complications in any
      of these children. There was no surgery for secondary displacement. Full range of
      motion was obtained in all patients at the final follow-up. DISCUSSION: The
      outcome of conservative treatment of closed diaphyseal forearm fractures, without
      overlapping fragments was excellent. However, reduction is usually performed in
      the operating room by orthopedic surgeons under general anesthesia and requires
      hospitalization, which is very expensive. The results of this study show that
      high quality care may be obtained in the ED by a trained and experienced team.
      These results are similar to those for distal metaphyseal fractures, which could
      extend the indications for reduction in the ED. LEVEL OF EVIDENCE: Level IV.
      Retrospective study.

PMID- 26198019
TI  - Postural instability in Parkinson Disease: to step or not to step.
AB  - Postural instability is a key feature of Parkinson Disease that is associated
      with falls and morbidity. We designed a pull apparatus to quantitatively measure
      the force needed to pull subjects off-balance. Thirteen Controls and eight
      individuals with Parkinson Disease (PD) were evaluated. All individuals with PD
      reported subjective symptoms of postural instability and were symptomatic for
      approximately 9.4years when tested. No significant differences were found between
      Controls and PD subjects in the magnitude of force required to pull them off
      balance. None of the Controls fell and all took a step into the direction of pull
      to maintain their balance. 59% of the time PD subjects fell because they did not
      take a step in the direction of pull to maintain their center of mass (COM) over
      their feet, thus indicating a deficiency in postural reflexes. If they fell on
      the first pull, PD subjects did not show a learning effect when pulled multiple
      times in the same direction. The utility of the Pull Test to detect postural
      instability is related to the subject's behavioral response, not the force needed
      to pull them off balance. Our findings may also help explain certain features of
      the PD gait as an attempt by subjects to avoid postural instability by not
      placing their COM in gravitationally unstable positions.

PMID- 26198020
TI  - Neurological involvement and characterization in acquired hemophagocytic
      lymphohistiocytosis in adulthood.
AB  - OBJECTIVE: To describe the neurological and neuroradiological features of
      acquired hemophagocytic lymphohistiocytosis (HLH) in adulthood by reporting a
      series of cases. METHODS: Ten consecutive patients who were diagnosed with HLH at
      Medstar Georgetown University Hospital and Walter Reed National Military Medical
      Center were evaluated for neurological involvement. All underwent clinical
      neurological evaluation, and when indicated CSF analysis and MR imaging of the
      brain. Data were gathered and analyzed retrospectively. RESULTS: Seven of the ten
      patients with HLH had neurological involvement. Mean age at onset was 50 (range:
      21 to 73). Four patients were males. Prominent clinical features included mild to
      severe encephalopathy and seizures. Other findings included hemiparesis and
      spastic tetraparesis. Neuroimaging revealed a wide spectrum of abnormalities
      including cortical and subcortical edema, gadolinium enhancement, hemorrhage, and
      diffusion restriction. Basal ganglia involvement was present in four out of seven
      patients. Three patients died due to multisystem organ failure, and the other
      patients displayed varying degrees of recovery. CONCLUSIONS: The neurological
      features of acquired HLH in adults have not been previously reported. These seven
      patients demonstrate the spectrum of neurological involvement that can occur. The
      diagnosis of HLH should be considered in patients who are systemically ill with
      unexplained fevers and hyperferritinemia who have evidence of inflammation in the
      CNS.

PMID- 26198021
TI  - Altered expression of metabolic proteins and adipokines in patients with
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease
      characterized by the loss of upper cortical and lower motor neurons. ALS causes
      death within 2-5years of diagnosis. Diet and body mass index influence the
      clinical course of disease, however there is limited information about the
      expression of metabolic proteins and fat-derived cytokines (adipokines) in ALS.
      In healthy controls and subjects with ALS, we have measured levels of proteins
      and adipokines that influence metabolism. We find altered levels of active
      ghrelin, gastric inhibitory peptide (GIP), pancreatic polypeptide (PP), lipocalin
      2, plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6) and 8 (IL-8),
      and tumor necrosis factor alpha (TNFalpha) in the plasma of ALS patients relative
      to controls. We also observe a positive correlation between the expression of
      plasma nerve growth factor (NGF) relative to disease duration, and an inverse
      correlation between plasma glucagon and the ALS functional rating scale-revised
      (ALSFRS-R). Further studies are required to determine whether altered expression
      of metabolic proteins and adipokines contribute to motor neuron vulnerability and
      how these factors act to modify the course of disease.

PMID- 26198022
TI  - A Kinetic Study of DDGS Hemicellulose Acid Hydrolysis and NMR Characterization of
      DDGS Hydrolysate.
AB  - Liquid hot water (LHW) extraction was used as a pretreatment method to separate
      the hemicellulose fraction from dried distiller's grain with solubles (DDGS) into
      liquid phase. Acid hydrolysis using 3.264 % w/w sulfuric acid at 130  degrees C
      was performed to convert polysaccharides in LHW extract to monosaccharides. The
      structure characterization of DDGS in anomeric carbon region based on proton NMR
      and heteronuclear single quantum coherence (HSQC) during acid hydrolysis was
      studied in this work. It reveals that the sugar units in DDGS hemicelluloses are
      constructed with (1-4)-beta-D-xylopyranose and alpha-L-arabinofuranosyl residues.
      A kinetic model is included to explain the changing concentration of monomer,
      oligomer, and sugar units. The model was further tested based on the changing
      concentration of five carbon sugar units during hydrolysis.

PMID- 26198023
TI  - Periplasmic Export of Bile Salt Hydrolase in Escherichia coli by the Twin
      Arginine Signal Peptides.
AB  - Bile salt hydrolase (BSH, EC 3.5.1.24) is considered as an ideal way with lower
      cost and less side effects to release the risk of coronary heart disease caused
      by hypercholesterolemia. As bile salt hydrolase from Lactobacillus plantarum BBE7
      could not be efficiently exported by PelB signal peptide of the general secretory
      (Sec) pathway, three twin-arginine signal peptides from twin-arginine
      translocation (Tat) pathway were synthesized, fused with bsh gene, inserted into
      expression vectors pET-20b(+) and pET-22b(+), and transformed into four different
      Escherichia coli hosts, respectively. Among the 24 recombinant bacteria obtained,
      E. coli BL21 (DE3) pLysS (pET-20b(+)-dmsA-bsh) showed the highest BSH activity in
      periplasmic fraction, which was further increased to 1.21 +/- 0.03 U/mL by
      orthogonal experimental design. And, signal peptide dimethyl sulfoxide reductase
      subunit DmsA (DMSA) had the best activity of exported BSH. More importantly, the
      presence of BSH in the periplasm had proven to be caused by the export rather
      than cell leakage. For the first time, we report the periplasmic expression of
      BSH by signal peptides from the Tat pathway. This will lay a solid foundation for
      the purification and biochemical characterization of BSH from the supernatant,
      and strategies adopted here could be used for the periplasmic expression of other
      proteins in E. coli.

PMID- 26198024
TI  - Cloning and Characterization of a Novel Agarase from a Newly Isolated Bacterium
      Simiduia sp. Strain TM-2 Able to Degrade Various Seaweeds.
AB  - A new bacterial strain capable of reducing thalli of various seaweeds (red,
      green, and brown algae) was isolated from marine sediments of Uozu in Toyama
      Prefecture, Japan. We designated the strain Simiduia sp. TM-2 based on analyses
      of the 16S rRNA gene and gyrB gene sequences and its biochemical and
      morphological characteristics. Zymography methods revealed numerous active bands
      of alginate lyases, cellulases, and agarases in the cells and culture
      supernatants of TM-2, showing that the strain possessed multiple polysaccharide
      lyases. A novel agarase gene (agaTM2) was cloned from TM-2 and expressed in
      Escherichia coli. The resulting DNA sequence contained an open reading frame of
      1764 bp that encoded a protein of 587 amino acids with an estimated molecular
      mass of 64 kDa and pI of 4.62. The deduced amino acid sequence, AgaTM2, had a
      typical signal peptide followed by a glycoside hydrolase family 16 catalytic
      domain and two carbohydrate-binding modules 6. A BLAST search indicated that
      AgaTM2 shared 75.5 % amino acid sequence identity with agarase from Simiduia
      agarivorans SA1. The cloned and purified AgaTM2 protein showed optimal activity
      at 35  degrees C and pH 8.0, and its thermostability increased in the presence of
      calcium ions. AgaTM2 degraded agarose to tetraose and hexaose.

PMID- 26198025
TI  - Statins for people at low risk.

PMID- 26198026
TI  - Clinical Profile of Athletes With Hypertrophic Cardiomyopathy.
AB  - BACKGROUND: The phenotype of individuals with hypertrophic cardiomyopathy (HCM)
      who exercise regularly is unknown. This study characterized the clinical profile
      of young athletes with HCM. METHODS AND RESULTS: The electrical, structural, and
      functional cardiac parameters from 106 young (14-35 years) athletes with HCM were
      compared with 101 sedentary HCM patients. A subset of athletes with HCM
      exhibiting morphologically mild (13-16 mm), concentric disease was compared with
      55 healthy athletes with mild physiological left ventricular hypertrophy (LVH).
      Most athletes with HCM (96%) exhibited T-wave inversion and had milder LVH
      (15.8+/-3.4 mm versus 19.7+/-6.5 mm, P<0.001), larger left ventricular cavity
      dimensions (47.8+/-6.0 mm versus 44.3+/-7.7 mm, P<0.001), and superior indices of
      diastolic function (average E/E' 7.9+/-2.4 versus 10.7+/-3.9, P<0.001) compared
      with sedentary HCM patients. In athletes with HCM, LVH was frequently (36%)
      confined to the apex and only 15 individuals (14%) exhibited mild concentric LVH
      mimicking physiological LVH. In these 15 athletes, conventional structural and
      functional cardiac parameters showed modest sensitivity and specificity for
      differentiating HCM from physiological LVH: 13% had a left ventricular cavity >54
      mm, 87% had a left atrium <=40, and 100% had an E/E' <12. CONCLUSIONS: Athletes
      with HCM exhibit less LVH, larger left ventricular cavities, and normal indices
      of diastolic function compared with sedentary patients. Only a minority of
      athletes with HCM constitute the conventional gray zone of mild, concentric LVH.
      In this minority, conventional echocardiographic parameters alone are
      insufficient to differentiate HCM from physiological LVH and should be
      complemented by additional structural and functional assessments to minimize the
      risk of false reassurance.

PMID- 26198027
TI  - Optical properties and light irradiance of monolithic zirconia at variable
      thicknesses.
AB  - OBJECTIVES: The aims of this study were to: (1) estimate the effect of polishing
      on the surface gloss of monolithic zirconia, (2) measure and compare the
      translucency of monolithic zirconia at variable thicknesses, and (3) determine
      the effect of zirconia thickness on irradiance and total irradiant energy.
      METHODS: Four monolithic partially stabilized zirconia (PSZ) brands; Prettau(r)
      (PRT, Zirkonzahn), Bruxzir(r) (BRX, Glidewell), Zenostar(r) (ZEN, Wieland),
      Katana(r) (KAT, Noritake), and one fully stabilized zirconia (FSZ); Prettau
      Anterior(r) (PRTA, Zirkonzahn) were used to fabricate specimens (n=5/subgroup)
      with different thicknesses (0.5, 0.7, 1.0, 1.2, 1.5, and 2.0mm). Zirconia core
      material ICE(r) Zircon (ICE, Zirkonzahn) was used as a control. Surface gloss and
      translucency were evaluated using a reflection spectrophotometer. Irradiance and
      total irradiant energy transmitted through each specimen was quantified using
      MARC(r) Resin Calibrator. All specimens were then subjected to a standardized
      polishing method and the surface gloss, translucency, irradiance, and total
      irradiant energy measurements were repeated. Statistical analysis was performed
      using two-way ANOVA and post-hoc Tukey's tests (p<0.05). RESULTS: Surface gloss
      was significantly affected by polishing (p<0.05), regardless of brand and
      thickness. Translucency values ranged from 5.65 to 20.40 before polishing and
      5.10 to 19.95 after polishing. The ranking from least to highest translucent
      (after polish) was: BRX=ICE=PRT<ZEN<KAT<PRTA (p<0.05). The ranking from least to
      highest total irradiant energy was: BRX<PRT<ICE=ZEN<KAT=PRTA (p<0.05). There was
      an inverse relationship between translucency, irradiant energy, and thickness of
      zirconia and the amount was brand dependent (p<0.05). SIGNIFICANCE: Brand
      selection, thickness, and polishing of monolithic zirconia can affect the
      ultimate clinical outcome of the optical properties of zirconia restorations. FSZ
      is relatively more polishable and translucent than PSZ.

PMID- 26198028
TI  - Adherence to cancer prevention guidelines in South Africa is associated with
      health care access.
AB  - BACKGROUND: Cancer prevention guidelines have been developed to improve knowledge
      and adherence to modifiable cancer risk factors. The implementation of these
      guidelines has largely been studied in North American and European populations.
      The aim of this study was to examine the association between health care access
      and adherence to the World Cancer Research Fund/American Institute for Cancer
      Research (WCRF/AICR) cancer prevention guidelines in South Africa, where the
      cancer incidence is rising. METHODS: Data from the 2003 South Africa World Health
      Survey was used to assess adherence to WCRF/AICR cancer prevention guidelines on
      alcohol, body mass index, nutrition, physical activity and smoking. Health care
      affordability, availability, accessibility, accommodation and acceptability in
      the past 12 months were assessed via self-report. RESULTS: Residing in a high
      socio-economic status household (affordability), visiting a non-governmental
      health care facility (availability), perception of health care provider skills as
      adequate (accommodation) and lack of perception of worse treatment based on
      social class (acceptability) were each associated with higher levels of adherence
      to the WCRF/AICR guidelines. CONCLUSIONS: In South Africa, better access to
      health care is associated with better patient adherence to cancer prevention
      guidelines. Future studies and efforts can focus on improving access to quality
      health care in this population.

PMID- 26198029
TI  - Lip sync conferences.

PMID- 26198030
TI  - The role of BAFF in the progression of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a common autoimmune disease that is marked by a
      systemic inflammatory reaction and joint erosions. Elevated levels of B cell
      activating factor (BAFF) have been detected in the serum and synovial fluid of RA
      patients. Moreover, the levels of BAFF increase in cases of autoimmune disease
      and are correlated with the level of disease activity. As an innate cytokine
      mediator, BAFF affects the immune response of the synovial microenvironment. In
      this review, we consider recent observations of BAFF and its receptors in RA
      progression, as well as the effects of BAFF on the cell-cell interactions
      network. We also summarize the clinical development of BAFF antagonists for the
      treatment of RA. 

PMID- 26198031
TI  - TNF Apoptosis Protection Fraction (TAPF) prevents apoptosis induced by TNF, but
      not by Fas or TRAIL, via NF-kappaB-induced increase in cFLIP.
AB  - Tumor Necrosis Factor alpha (TNFalpha) induces both the apoptotic pathway and
      anti-apoptotic factors. Incubation of human dermal fibroblasts with TAPF (TNF
      Apoptosis Protection Fraction) protects them from apoptosis induced by the
      subsequent addition of TNF and cycloheximide (CHX). TAPF does not protect against
      apoptosis induced by CHX in combination with either TRAIL (TNF related apoptosis
      inducing ligand) or an agonistic Fas antibody, or against apoptosis induced by
      the chemotherapeutic agent doxorubicin. Incubation with TAPF does not affect the
      quantity of TNF that binds to the cell. TAPF prevents TNF-induced cleavage of
      caspases 8, 9, 3 and 7 and the apoptotic substrate PARP (poly-ADP ribose
      polymerase), but has no effect when these molecules are induced by an agonistic
      Fas antibody. TAPF induces rapid phosphorylation of the NF-kappaB/p65 (nuclear
      factor-kappaB) transcription factor at serine 536 which is indicative of its
      activation. TAPF increases the expression of cFLIP (cellular FLICE-inhibitory
      protein) which is a potent inhibitor of apoptosis that acts by preventing the
      cleavage of caspase 8. This increase in cFLIP is coincident with protection from
      TNF-induced apoptosis. Decreasing cFLIP levels using shRNA (short hairpin RNA)
      decreases protection by TAPF. TAPF also induced the anti-apoptotic A20 protein.
      These data indicate that TAPF protects human dermal fibroblasts from TNF-induced
      apoptosis by induction of cFLIP and subsequent inhibition of caspase 8 cleavage. 

PMID- 26198032
TI  - Cigarette smoke affects IL-17A, IL-17F and IL-17 receptor expression in the lung
      tissue: Ex vivo and in vitro studies.
AB  - Cigarette smoke is a risk factor for Chronic Obstructive Pulmonary Disease
      (COPD). Th-17 cytokines are involved in the pathogenesis of COPD. We aimed to
      evaluate the role of cigarette smoke on the expression of IL-17A, IL-17F and IL
      17R in airways of COPD patients. Epithelial and subepithelial immunoreactivity
      for IL-17A, IL-17F and IL-17R was assessed in surgical specimens from COPD
      patients (n=15) and from healthy subjects (HC) (n=10) by immunohistochemistry. In
      vitro, human epithelial cell line 16HBE and A549 as well as PBMC from normal
      donors were stimulated with cigarette smoke extract (CSE) (0%, 2.5%, 5%, 10%) to
      evaluate the IL-17A, IL-17F and IL-17R expression by flow cytometry. Furthermore,
      rhIL-17A and CSE stimulation was evaluated on proliferation and apoptosis in
      16HBE and in A549. In central and distal airways immunoreactivity for IL-17A, IL
      17F and IL-17R significantly increased in the epithelium and IL-17A in the
      subepithelium from COPD than in HC. In distal airway, immunoreactivity for IL-17F
      increased in the subepithelium of COPD than in HC. IL-17A immunoreactivity
      positively correlate with IL-17R and total pack years in the epithelium from
      central and distal airways of COPD patients. In vitro, CSE stimulation
      significantly increased IL-17F and IL-17R in 16HBE (2.5%) and A549 (5%) while IL
      17A and IL-17F in PBMC (10%). IL-17A and CSE stimulation, rather than CSE or rhIL
      17A alone, significantly increased proliferation in 16HBE and apoptosis in A549.
      Cigarette smoke increases Th17 immunity in lung tissue of COPD patients,
      promoting the mechanism of proliferation and apoptosis in airway epithelial
      cells. 

PMID- 26198035
TI  - How to Use the FORTA ("Fit fOR The Aged") List to Improve Pharmacotherapy in the
      Elderly.
AB  - BACKGROUND: Multimorbidity and polypharmacy are threats to elderly patients;
      improvement of medication is important and a novel listing approach (the FORTA
      list) should support this in clinical practice. Here we aim to describe
      procedural details of successful application of FORTA. FORTA labels range from A
      (indispensable), B (beneficial), C (questionable) to D (avoid), depending on
      evidence for safety, efficacy and overall age-appropriateness. As implicit tool
      it is only applicable if medical details of the patient are known; the drug
      selection process and secondary assessments are compiled into a manual for
      successful, embedded use of FORTA. DISCUSSION: A flow chart is developed for the
      complex process of medication in the elderly starting from history taking and
      diagnostic assessment including disease grading. This is the base for FORTA
      assisted selection of drugs to avoid overtreatment (drug not necessary),
      undertreatment (condition not or not sufficiently treated by positively labeled
      drugs) or mistreatment (drugs indicated, but negatively rather than positively
      labeled drug chosen). Selection is followed by secondary analyses, e. g.
      regarding contraindications (e. g. allergies), former drug responses,
      interactions, route of application, duration and dosing (e. g. renal adaptation).
      This may lead to iterative process optimization. The medication scheme is updated
      in reflection of clinical effects (e. g. blood pressure) and side effects (e. g.
      dizziness). CONCLUSION: The FORTA approach as an implicit tool should be embedded
      into the diagnostic and therapeutic workup of elderly patients and can give
      pivotal hints for the choice of medications; however it should not be seen as an
      isolated instrument.

PMID- 26198036
TI  - Fenugreek Seed Extract Prevents Fat Deposition in Monosodium Glutamate (MSG)
      Obese Rats.
AB  - AIM: To evaluate the preventive effects of an aqueous extract of Trigonella
      foenum-graecum seeds (AqE-TFG) on fat deposition and dyslipidemia in monosodium
      glutamate (MSG)-obese rats. METHODS: Neonatal male Wistar rats were injected with
      MSG (4 g/kg b. w., subcutaneously) from day 2 to 14 after birth, on alternate
      days. From day 43 to 70, MSG treated rats were administered orally with AqE-TFG
      (0.5 and 1.0 g/kg b. w.). The anthropometric and biochemical parameters were
      analyzed on day 71. RESULTS: Treatment with AqE-TFG produced significant (P <
      0.05 or P < 0.01) reduction in body weight gain, Lee's index, white adipose
      tissue (WAT) weights, adiposity index, blood glucose, serum insulin, leptin,
      lipids (low density lipoprotein cholesterol and very low density lipoprotein
      cholesterol), cardiac risk indexes (atherogenic index and coronary risk index),
      and homeostatic model assessment index. AqE-TFG treatment restored the activities
      of liver and epididymal WAT lipogenic enzymes (fatty acid synthetase and glucose
      6-phosphate dehydrogenase) towards normal levels. Histological studies of liver
      also supported the experimental findings. CONCLUSION: These findings demonstrated
      the preventive effect of AqE-TFG on fat deposition and dyslipidemia possibly by
      improvement in glucose and lipid metabolism, enhancement of insulin sensitivity
      and down regulation of lipogenic enzymes.

PMID- 26198034
TI  - The role of CaMKII in diabetic heart dysfunction.
AB  - Diabetes mellitus (DM) is an increasing epidemic that places a significant burden
      on health services worldwide. The incidence of heart failure (HF) is
      significantly higher in diabetic patients compared to non-diabetic patients. One
      underlying mechanism proposed for the link between DM and HF is activation of
      calmodulin-dependent protein kinase (CaMKIIdelta). CaMKIIdelta mediates ion
      channel function and Ca(2+) handling during excitation-contraction and excitation
      transcription coupling in the myocardium. CaMKIIdelta activity is up-regulated in
      the myocardium of diabetic patients and mouse models of diabetes, where it
      promotes pathological signaling that includes hypertrophy, fibrosis and
      apoptosis. Pharmacological inhibition and knockout models of CaMKIIdelta have
      shown some promise of a potential therapeutic benefit of CaMKIIdelta inhibition,
      with protection against cardiac hypertrophy and apoptosis reported. This review
      will highlight the pathological role of CaMKIIdelta in diabetes and discuss
      CaMKIIdelta as a therapeutic target in DM, and also the effects of exercise on
      CaMKIIdelta. 

PMID- 26198037
TI  - Medium-based optimization of an organic solvent-tolerant extracellular lipase
      from the isolated halophilic Alkalibacillus salilacus.
AB  - A haloalkaliphilic solvent-tolerant lipase was produced from Alkalibacillus
      salilacus within 48 h of growth in liquid medium. An overall 4.9-fold enhanced
      production was achieved over unoptimized media after medium optimization by
      statistical approaches. Plackett-Burman screening suggested lipase production
      maximally influenced by olive oil, KH2PO4, NaCl, and glucose; and response
      surface methodology predicted the appropriate levels of each parameter. Produced
      lipase was highly active and stable over broad ranges of temperature (15-65 
      degrees C), pH (4.0-11.0), and NaCl concentration (0-30 %) showing excellent
      thermostable, pH-stable, and halophilic properties. The enzyme was optimally
      active at pH 8.0 and 40  degrees C. Majority of cations, except some like Co(2+)
      and Al(3+) were positive signals for lipase activity. In addition, the presence
      of chemical agents and organic solvents with different log P ow was well
      tolerated by the enzyme. Finally, efficacy of lipase-mediated esterification of
      various alcohols with oleic acid in organic solvents was studied.

PMID- 26198038
TI  - Burkholderia pseudomallei Capsular Polysaccharide Recognition by a Monoclonal
      Antibody Reveals Key Details toward a Biodefense Vaccine and Diagnostics against
      Melioidosis.
AB  - Burkholderia pseudomallei is the bacterium responsible for melioidosis, an
      infectious disease with high mortality rates. Since melioidosis is a significant
      public health concern in endemic regions and the organism is currently classified
      as a potential biothreat agent, the development of effective vaccines and rapid
      diagnostics is a priority. The capsular polysaccharide (CPS) expressed by B.
      pseudomallei is a highly conserved virulence factor and a protective antigen.
      Because of this, CPS is considered an attractive antigen for use in the
      development of both vaccines and diagnostics. In the present study, we describe
      the interactions of CPS with the murine monoclonal antibody (mAb) 4C4 using a
      multidisciplinary approach including organic synthesis, molecular biology
      techniques, surface plasmon resonance, and nuclear magnetic spectroscopy. Using
      these methods, we determined the mode of binding between mAb 4C4 and native CPS
      or ad hoc synthesized capsular polysaccharide fragments. Interestingly, we
      demonstrated that the O-acetyl moiety of CPS is essential for the interaction of
      the CPS epitope with mAb 4C4. Collectively, our results provide important
      insights into the structural features of B. pseudomallei CPS that enable antibody
      recognition that may help the rational design of CPS-based vaccine candidates. In
      addition, our findings confirm that the mAb 4C4 is suitable for use in an
      antibody-based detection assay for diagnosis of B. pseudomallei infections. 

PMID- 26198033
TI  - POPULATION GENETICS. Genomic evidence for the Pleistocene and recent population
      history of Native Americans.
AB  - How and when the Americas were populated remains contentious. Using ancient and
      modern genome-wide data, we found that the ancestors of all present-day Native
      Americans, including Athabascans and Amerindians, entered the Americas as a
      single migration wave from Siberia no earlier than 23 thousand years ago (ka) and
      after no more than an 8000-year isolation period in Beringia. After their arrival
      to the Americas, ancestral Native Americans diversified into two basal genetic
      branches around 13 ka, one that is now dispersed across North and South America
      and the other restricted to North America. Subsequent gene flow resulted in some
      Native Americans sharing ancestry with present-day East Asians (including
      Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican"
      relict populations, including the historical Mexican Pericues and South American
      Fuego-Patagonians, are not directly related to modern Australo-Melanesians as
      suggested by the Paleoamerican Model. 

PMID- 26198043
TI  - Chlorpyrifos Induces MLL Translocations Through Caspase 3-Dependent Genomic
      Instability and Topoisomerase II Inhibition in Human Fetal Liver Hematopoietic
      Stem Cells.
AB  - Household pesticide exposure during pregnancy has been associated with a more
      than 2-fold increased risk in infant leukemia, and chlorpyrifos (CPF) is among
      the most frequently applied insecticides. During early fetal development, liver
      is a hematopoietic organ with majority of cells being CD34(+) hematopoietic stem
      cells (CD34(+)HSC). The in utero injury to CD34(+)HSC has been known to underlie
      the pathogenesis of several blood disorders, often involving rearrangements of
      the mixed-lineage leukemia (MLL) gene on 11q23. In this study, we evaluated the
      leukemogenic potential of CPF in human fetal liver-derived CD34(+)HSC.
      Specifically, exposure to 10 MUM CPF led to decrease in viability, inhibition in
      proliferation and induction of DNA double-strand breaks (DSBs) and occurrence of
      MLL(+) rearrangements. In particular, we observed CPF-mediated cell cycle
      disturbance as shown by G0/G1 arrest, in contrast to etoposide (VP-16), an
      anticancer drug used as a positive control and known to induce G2/M arrest.
      Further study on mechanisms underlying DNA DSBs and MLL(+) rearrangements
      revealed that CPF might act as topoisomerase II poison, a mechanism of action
      similar to VP-16. On the other hand, CPF was also shown to induce early apoptosis
      through active caspase-3 activation, a pathway known to underlie DNA DSBs and
      MLL(+) translocations. Our data indicate that in utero injury of CD34(+)HSC by
      CPF may contribute to the increased risk of infant leukemia. Future work will
      elucidate the mechanism and the type of CPF-induced MLL(+) translocations in HSC.

PMID- 26198044
TI  - Cellular Accumulation and Toxic Effects of Bile Acids in Cyclosporine A-Treated
      HepaRG Hepatocytes.
AB  - Alteration of bile acid (BA) profiles and secretion by cholestatic drugs
      represents a major clinical issue. Species differences exist in BA composition,
      synthesis, and regulation; however presently, there is no in vitro reproducible
      cell model to perform studies on BAs in humans. We have evaluated the capacity of
      the human HepaRG cell line to synthesize, conjugate, and secrete BAs, and
      analyzed changes in BA content and profile after cyclosporine A (CsA) treatment.
      Our data show that HepaRG cells produced normal BAs at daily levels comparable,
      though in different proportions, to those measured in primary human hepatocytes.
      A 4-h treatment with CsA led to BA accumulation and profile changes associated
      with occurrence of cholestatic features, while after 24 h BAs were decreased in
      cell layers and increased in media. The latter effects resulted from reduced
      function of BA uptake transporter (Na(+)-taurocholate cotransporting
      polypeptide), reduced expression of BA metabolizing enzymes, including cytochrome
      P4507A1, cytochrome P4508B1, and cytochrome P45027A1, and induction of
      alternative basolateral transporters. Noteworthy, HepaRG cells incubated in a 2%
      serum-supplemented medium showed dose-dependent accumulation of the cytotoxic BA
      lithocholic acid in a nonsulfoconjugated form associated with early inhibition of
      the canalicular transporter MRP2 and sulfotransferase 2A1. In summary, our data
      bring the first demonstration that an in vitro human liver cell line is able to
      produce and secrete conjugated BAs, and to accumulate endogenous BAs transiently,
      concomitantly to occurrence of various other cholestatic features following CsA
      treatment. Retention of the hydrophobic lithocholic acid supports its toxic role
      in drug-induced cholestasis. Overall, our results argue on the suitability of
      HepaRG cells for investigating mechanisms involved in the development of the
      disease.

PMID- 26198045
TI  - MicroRNA-495 downregulates FOXC1 expression to suppress cell growth and migration
      in endometrial cancer.
AB  - MicroRNAs (miRNAs) are a class of noncoding RNAs and function as key regulators
      of gene expression at the post-transcriptional level. In this study, we found
      that miR-495 reduces cell growth, induces apoptosis and suppresses the migration
      of endometrial cancer by directly inhibiting FOXC1 expression. Further analysis
      revealed that FOXC1 promotes growth and migration and functions as an oncogene in
      vitro. FOXC1 overexpression reversed the cellular responses mediated by miR-495
      in endometrial cancer cells. We also found that miR-495 suppresses the growth of
      endometrial cancer in vivo. Altogether, these results indicate that miR-495 acts
      as a tumour suppressor gene by targeting FOXC1 at the post-transcriptional level
      in endometrial cancer. 

PMID- 26198046
TI  - Study of single nucleotide polymorphisms of tumour necrosis factors and HSP genes
      in nasopharyngeal carcinoma in North East India.
AB  - Nasopharyngeal carcinoma (NPC) is an epithelial tumour with a distinctive racial
      and geographical distribution. High incidence of NPC has been reported from
      China, Southeast Asia, and northeast (NE) region of India. The immune mechanism
      plays incredibly role in pathogenesis of NPC. Tumour necrosis factors (TNFs) and
      heat shock protein 70 (HSP 70) constitute significant components of innate as
      well as adaptive host immunity. Multi-analytical approaches including logistic
      regression (LR), classification and regression tree (CART) and multifactor
      dimensionality reduction (MDR) were applied in 120 NPC cases and 100 controls to
      explore high order interactions among TNF-alpha (-308 G>A), TNF beta (+252 A>G),
      HSP 70-1 (+190 G>C), HSP 70-hom (+2437 T>C) genes and environmental risk factors.
      TNF beta was identified as the primary etiological factor by all three analytical
      approaches. Individual analysis of results showed protective effect of TNF beta
      GG genotype (adjusted odds ratio (OR2) = 0.27, 95 % CI = 0.125-0.611, P = 0.001),
      HSP 70 (+2437) CC genotype (OR2 = 0.17, 95 % CI = 0.0430.69, P = 0.013), while AG
      genotype of TNF beta was found significantly associated with risk of NPC (OR2 =
      1.97, 95 % CI = 1.019-3.83, P = 0.04). Analysis of environmental factors
      demonstrated association of alcohol consumption, living in mud houses and use of
      firewood for cooking as major risk factors for NPC. Individual haplotype
      association analysis showed significant risk associated with GTGA haplotype (OR =
      68.61, 95 % CI = 2.47-190.37, P = 0.013) while a protective effect with CCAA and
      GCGA haplotypes (OR = 0.19, 95 % CI = 0.05-0.75, P = 0.019; OR = 0.01 95 % CI =
      0.05-0.30, P = 0.007). The multi-analytical approaches applied in this study
      helped in identification of distinct gene-gene and gene-environment interactions
      significant in risk assessment of NPC. 

PMID- 26198047
TI  - H19-derived miR-675 contributes to bladder cancer cell proliferation by
      regulating p53 activation.
AB  - Long noncoding RNA 19 (H19) has been shown to promote bladder cancer cell
      proliferation and metastasis. However, little is known about how miR-675, mature
      product of H19, contributes to bladder cancer cell proliferation. In this study,
      we first evaluated the expression of miR-675 in bladder cancer tissues by
      quantitative real-time PCR (qRT-PCR) and defined its biological functions by flow
      cytometry and Western blotting. We found that miR-675 expression levels were
      remarkably increased in bladder cancer tissues as compared with adjacent
      noncancerous tissues or normal bladder tissue from health donors; moreover,
      enhanced miR-675 expression was also observed in bladder cancer cell lines.
      Ectopic expression of H19 significantly increased bladder cancer cell
      proliferation and miR-675 expression in vitro. Furthermore, overexpression of miR
      675 promoted bladder cancer cell proliferation, while suppression of miR-675
      induced G1 phase cell cycle arrest and promoted cell apoptosis. Western blotting
      analysis further identified that miR-675 inhibited p53 activation, decreased the
      ratio of Bax/Bcl-2 and cyclin D1 expression in bladder cancer cells; those
      effects may result in the abnormal proliferation of bladder cancer cells. In
      conclusion, abnormal enhanced miR-675 expression increases bladder cancer growth
      by regulating p53 activation, and thus may be helpful in the development of
      effective treatment strategies for bladder cancer. 

PMID- 26198048
TI  - ITGA2B and ITGA8 are predictive of prognosis in clear cell renal cell carcinoma
      patients.
AB  - Integrins play an important role in cancer growth and metastasis. This study
      aimed at determining the predictive ability of integrins and associated genes
      identified through molecular network in clear cell renal cell carcinoma. A total
      of 525 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohorts were
      collected in this study. The expression profile of integrins and related genes
      were obtained from the TCGA RNAseq database. Clinicopathological characteristics,
      including age, gender, tumor size, tumor node metastasis (TNM), tumor grade,
      stage, laterality, and overall survival were collected. Cox proportional hazards
      regression model as well as Kaplan-Meier curve were used to assess the relative
      factors. Genes of integrin family that showed certain correlations with overall
      survival (OS) were further validated in the Fudan University Shanghai Cancer
      Center (FUSCC) cohort. In the TCGA cohort, after Cox proportional hazards
      analysis, ITGA2B (hazards ratio (HR) = 1.232, 95 % CI 1.097 to 1.383) and ITGA8
      (HR = 0.804, 95 % CI 0.696 to 0.930) were shown predictive of ccRCC prognosis.
      Low ITGA8 expression was associated with poor prognosis for OS (log-rank test, p
      < 0.0001), while high level of ITGA2B expression was correlated with poor
      prognosis for OS (log-rank test, p < 0.0001). This finding was validated in FUSCC
      cohort (log-rank test, all p < 0.05). As a result, low ITGA8 expression was
      associated with poor prognosis for OS (log-rank test, p = 0.0053), while high
      level of ITGA2B expression was correlated with poor prognosis for OS (log-rank
      test, p < 0.0001). Plus, low ITGA8 expression was associated with poor prognosis
      for disease-free survival (DFS) in the TCGA cohort (log-rank test, p < 0.0001).
      In the gene cluster network analysis, GIT1 and SHC1 associated with ITGA2B and
      ITGA8 were identified as independent predictive factors of overall survival of
      ccRCC. ITGA2B, ITGA8, GIT1, and SHC1 were identified as independent prognostic
      factors of overall survival of ccRCC. This method may act as a tool to reveal
      more prognostic-associated genes in ccRCC. 

PMID- 26198049
TI  - Upscaling the niche variation hypothesis from the intra- to the inter-specific
      level.
AB  - The "niche variation hypothesis" (NVH) predicts that populations with wider
      niches should display higher among-individual variability. This prediction
      originally stated at the intra-specific level may be extended to the inter
      specific level: individuals of generalist species may differ to a greater extent
      than individuals of a specialist species. We tested the NVH at intra- and inter
      specific levels based on a large diet database of three large herbivore feces
      collected in the field and analyzed using DNA metabarcoding. The three herbivores
      (roe deer Capreolus capreolus, chamois Rupicapra rupicapra and mouflon Ovis
      musimon) are highly contrasted in terms of sociality (solitary to highly
      gregarious) and diet. The NVH at the intraspecific level was tested by relating,
      for the same population, diet breadth and inter-individual variation across the
      four seasons. Compared to null models, our data supported the NVH both at the
      intra- and inter-specific levels. Inter-individual variation of the diet of
      solitary species was not larger than in social species, although social
      individuals feed together and could therefore have more similar diets. Hence, the
      NVH better explained diet breadth than other factors such as sociality. The
      expansion of the population niche of the three species was driven by resource
      availability, and achieved by an increase in inter-individual variation, and the
      level of inter-individual variability was larger in the generalist species
      (mouflon) than in the specialist one (roe deer). This mechanism at the base of
      the NVH appears at play at different levels of biological organization, from
      populations to communities. 

PMID- 26198051
TI  - Improving dimensional measurement from noisy atomic force microscopy images by
      non-local means filtering.
AB  - Quantitative evaluation of dimensional parameters from noisy atomic force
      microscopy (AFM) images was investigated. Non-local means (NLM) denoising was
      adopted to reduce noise and maintain fine image structures. Major tuning
      parameters in NLM filtering, such as the patch size and the window size, were
      optimized on simulated surface structures. The ability of dimensional evaluation
      from noisy data was demonstrated to be improved by almost 15 times. Finally, NLM
      filtering with optimal settings was applied on experimental AFM images, which
      were scanned on a patterned few-layer graphene specimen. Evaluations of the step
      height and the pattern size were verified to be much more accurate and robust.
      Such a data processing method can enhance the AFM dimensional measurements,
      particularly when the noise-level is reached.

PMID- 26198050
TI  - Vitrification of Rattus norvegicus immature cumulus-oocyte complexes using
      hyaluronic acid.
AB  - The aim of this study was to assess in vitro meiosis resumption and nuclear
      maturation of Rattus norvegicus oocytes after vitrification with different
      cryoprotective solutions. Cumulus-oocyte complexes (COCs) were exposed to an
      equilibration solution for 4 min placed in cryoprotective solutions for 1 min and
      vitrified in open pulled straws. Cryoprotective solutions were prepared with 15%
      ethylene glycol + 15% dimethyl sulfoxide + 0.5 M sucrose and different
      supplements, to form the following groups: G1, 20% fetal bovine serum in modified
      phosphate-buffered saline (mPBS); G2, 0.4% bovine serum albumine in mPBS; G3, 1%
      hyaluronic acid in mPBS; and G4, 0.4% polyvinyl alcohol in mPBS. Seven days after
      vitrification, the COCs from G1 to G4 were warmed and in vitro matured for 30 h
      along with the control group. Hoechst staining was performed to assess meiosis
      resumption and nuclear maturation rates. Control group showed higher meiosis
      resumption (77.88%) and nuclear maturation rates (55.75%) compared to all
      vitrified groups. Among the vitrified COCs, G3 showed the highest meiosis
      resumption and nuclear maturation rates (G1, 26.5 and 15.38%; G2, 22.12 and
      11.54%; G3, 34.55 and 20%; G4, 20.17 and 9.24%). Supplementation of the
      vitrification solution with 1% hyaluronic acid provided better results, compared
      to the other supplements. Hyaluronic acid can be useful to vitrify rat COCs
      associated with other cryoprotectant agents. 

PMID- 26198052
TI  - Subject- and resource-specific monitoring and proactive management of parallel
      radiofrequency transmission.
AB  - PURPOSE: Develop a practical comprehensive package for proactive management of
      parallel radiofrequency (RF) transmission. METHODS: With a constrained
      optimization framework and predictive models from a prescan based multichannel
      calibration, we presented a method supporting design and optimization of parallel
      RF excitation pulses that accurately obey the forward/reflected peak and average
      power limits of the RF power amplifiers in parallel transmit imaging experiments
      and Bloch simulations. Moreover, local SAR limits were incorporated into the
      parallel RF excitation pulses using electromagnetic field simulations. Virtual
      transmit coils concept for minimization of reflected power (effecting subject
      specific matching) was additionally demonstrated by leveraging experimentally
      calibrated power models. RESULTS: Incorporation of experimentally calibrated
      power prediction models resulted in accurate compliance with prescribed hardware
      and global specific absorption rate (SAR) limits. Incorporation of spatial
      average 10 g SAR models, facilitated by simplifying numerical approximations,
      provided assurance of patient safety. RF pulses designed with various constraints
      demonstrated excellent excitation fidelity-the normalized root-mean-square error
      of the simulated excitation profiles was 2.6% for the fully constrained pulses,
      comparable to that of the unconstrained pulses. An RF shimming example showed a
      reduction of the reflected-to-forward power ratio to 1.7% from a conventional
      approach's 8.1%. CONCLUSION: Using the presented RF pulse design method,
      effective proactive management of the multifaceted power and SAR limits was
      demonstrated in experimental and simulation studies. Magn Reson Med 76:20-31,
      2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26198053
TI  - Role of saposin C and D in auditory and vestibular function.
AB  - OBJECTIVES/HYPOTHESIS: Saposins are small proteins derived from a precursor
      protein, prosaposin. Each of the four saposins (A-D) is necessary for the
      activity of lysosomal glycosphingolipid hydrolases. Individual saposin mutations
      lead to lysosomal storage diseases, some of which are associated with hearing
      loss. Here we evaluate the effects of the loss of saposins C and D on auditory
      and vestibular function in transgenic mice. METHODS: Transgenic mice with either
      loss of saposin C function or a combined loss of saposin C + D function were
      studied. Light microscopy and immunofluorescence were used to evaluate histologic
      and morphologic changes in the auditory and vestibular organs. Acoustic brainstem
      response thresholds and distortion product otoacoustic emissions were used to
      study the auditory phenotype. RESULTS: A null mutation of saposin C did not
      result in any identifiable histologic changes or loss of hearing through
      postnatal day 55. Combined losses of saposins C and D similarly did not result in
      any changes in organ of Corti histology or loss of hearing. However, inclusions
      within the vestibular end organs was noted, consistent with afferent and efferent
      neuronal sprouting, although to a much milder degree than seen in the previously
      studied prosaposin knockout mouse. CONCLUSIONS: Loss of saposin C and D function,
      although causing mild phenotypic changes in the vestibular end organs, otherwise
      results in minimal functional impairment and no changes in the auditory system.
      It is more likely that the auditory and vestibular effects of the loss of
      prosaposin are mediated through the actions of saposin A and/or B. LEVEL OF
      EVIDENCE: NA.

PMID- 26198054
TI  - Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a
      Brazilian population with high African ancestry.
AB  - Nonsyndromic cleft lip with or without cleft palate (NSCL +/- P) is the most
      common orofacial birth defect, exhibiting variable prevalence around the world,
      often attributed to ethnic and environmental differences. Linkage analyses and
      genome-wide association studies have identified several genomic susceptibility
      regions for NSCL +/- P, mostly in European-derived or Asian populations. Genetic
      predisposition to NSCL +/- P is ethnicity-dependent, and the genetic basis of
      susceptibility to NSCL +/- P likely varies among populations. The population of
      Brazil is highly admixed, with highly variable ancestry; thus, the genetic
      determinants of NSCL +/- P susceptibility may be quite different. This study
      tested association of 8 single-nucleotide polymorphisms (SNPs), previously
      identified by genome-wide studies in other populations, with NSCL +/- P in a
      Brazilian population with high African ancestry. SNPs rs560426, rs642961,
      rs1530300, rs987525, rs3758249, rs7078160, rs17085106, and rs13041247 were
      genotyped in 293 Brazilian patients with NSCL +/- P and 352 unaffected Brazilian
      controls. Each sample was also genotyped for 40 biallelic short
      insertion/deletion polymorphic markers to characterize genetic ancestry. The
      average African ancestry background was 31.1% for the NSCL +/- P group and 36.7%
      for the control group. After adjustment for ancestry and multiple testing, the
      minor alleles of rs3758249 (OR: 1.58, 95% CI: 1.25-2.01, P = 0.0001) and
      rs7078160 (OR: 1.59, 95% CI: 1.21-2.07, P = 0.0002) were significantly associated
      with risk of NSCL +/- P. Polymorphisms located in IRF6 (rs642961) and 8q24
      (rs1530300 and rs987525) showed marginal associations in this Brazilian
      population with high African ancestry. These results indicate that rs3758249 at
      9q22 and rs7078160 at 10q25.3 represent risk loci for NSCL +/- P in the Brazilian
      population with high African ancestry.

PMID- 26198056
TI  - Risk assessment for anterior cruciate ligament injury.
AB  - INTRODUCTION: Anterior cruciate ligament tears are one of the most frequent soft
      tissue injuries of the knee. A torn anterior cruciate ligament leaves the knee
      joint unstable and at risk for further damage to other soft tissues manifested as
      pain, dislocation, and osteoarthritis. A better understanding of the anatomical
      details of knee joints suffering anterior cruciate ligament tears is needed to
      understand and develop prediction models for anterior cruciate ligament injury
      and/or tear. MATERIALS AND METHODS: Magnetic resonance images of 32 patients with
      anterior cruciate ligament tears and 40 patients with non-tears were evaluated
      from a physician group practice. Digital measurements of femoral condyle length,
      femoral notch width, anterior cruciate ligament width in the frontal and sagittal
      plane, and the anterior cruciate ligament length in the sagittal plane were taken
      in both groups to identify trends. Monte Carlo simulations were performed (n =
      2000) to evaluate the relationship between notch width index and sagittal width
      and to establish functional relationships among the anatomical parameters for
      potential injury risk. Sensitivity analysis performed shows the risk of anterior
      cruciate ligament injury a function of force and notch width index. RESULTS:
      Females have a significantly shorter anterior cruciate ligament when compared to
      that of males. The notch width index was also significantly different between
      torn and non-torn individuals. The NWI was not significantly different between
      genders (p value = 0.40). CONCLUSIONS: Anterior cruciate ligament injury has been
      shown to be caused by the forces which act on the ligament. These forces can
      result from hyperextension of the tibia or the internal rotation of tibia. The
      anatomical parameters of the knee joint (i.e., notch width index, anterior
      cruciate ligament width and length) have no role in the cause of an injury.

PMID- 26198057
TI  - Clinical outcomes following revision anterior shoulder arthroscopic capsulolabral
      stabilization.
AB  - INTRODUCTION: Traditionally surgeons have treated failed shoulder instability
      with open capsulolabral repair. Despite improved instrumentation, technique and
      familiarity in shoulder arthroscopy, few studies have reported the outcomes of
      arthroscopic revision shoulder instability repair. The purpose of this study was
      to assess clinical outcomes in patients following revision shoulder arthroscopic
      anterior capsulolabral stabilization. MATERIALS AND METHODS: Sixty-two patients
      (63 shoulders) with failure of primary instability repairs were treated with
      revision arthroscopic anterior shoulder stabilization at a mean follow-up of 46.9
      +/- 16.8 months (range 18-78). Clinical outcomes were evaluated using validated
      patient-reported outcome questionnaires including the American Shoulder and Elbow
      Surgeons score, Simple Shoulder Test, visual analog pain scale and Western
      Ontario Shoulder Instability Index. In addition, patients were queried for
      recurrent instability events (subluxation or dislocation) or revision surgery.
      RESULTS: At final follow-up, the mean postoperative Western Ontario Shoulder
      Instability normalized score was 80.1 +/- 18.7 (range 15.0-100). There were
      clinically significant improvements in American Shoulder and Elbow Surgeons
      scores, Simple Shoulder Test scores and ten-point visual analog scale for pain (P
      < 0.001). Recurrent instability occurred in 12 shoulders (19.0 %), with number of
      prior surgeries and hyperlaxity found to be significant risk factor for failure
      (P < 0.001 and P = 0.04, respectively). CONCLUSION: Revision arthroscopic
      anterior stabilization of the shoulder can result in satisfactory outcomes in
      appropriately selected patients who have failed previous capsulolabral repair. An
      increased number of prior surgeries and hyperlaxity are predictive of poor
      outcome. STUDY DESIGN: Case series, LOE IV.

PMID- 26198055
TI  - Enhanced epithelial to mesenchymal transition (EMT) and upregulated MYC in
      ectopic lesions contribute independently to endometriosis.
AB  - BACKGROUND: Epithelial to mesenchymal transition (EMT) is a process in which
      epithelial cells lose polarity and cell-to-cell contacts and acquire the
      migratory and invasive abilities of mesenchymal cells. These abilities are
      thought to be prerequisites for the establishment of endometriotic lesions. A
      hallmark of EMT is the functional loss of E-cadherin (CDH1) expression in
      epithelial cells. TWIST1, a transcription factor that represses E-cadherin
      transcription, is among the EMT inducers. SNAIL, a zinc-finger transcription
      factor, and its close relative SLUG have similar properties to TWIST1 and are
      thus also EMT inducers. MYC, which is upregulated by estrogens in the uterus by
      an estrogen response cis-acting element (ERE) in its promoter, is associated with
      proliferation in endometriosis. The role of EMT and proliferation in the
      pathogenesis of endometriosis was evaluated by analyzing TWIST1, CDH1 and MYC
      expression. METHODS: CDH1, TWIST1, SNAIL and SLUG mRNA expression was analyzed by
      qRT-PCR from 47 controls and 74 patients with endometriosis. Approximately 42
      ectopic and 62 eutopic endometrial tissues, of which 30 were matched samples,
      were collected during the same surgical procedure. We evaluated TWIST1 and MYC
      protein expression by immunohistochemistry (IHC) in the epithelial and stromal
      tissue of 69 eutopic and 90 ectopic endometrium samples, of which 49 matched
      samples were analyzed from the same patient. Concordant expression of
      TWIST1/SNAIL/SLUG and CDH1 but also of TWIST1 and MYC was analyzed. RESULTS: We
      found that TWIST1, SNAIL and SLUG are overexpressed (p < 0.001, p = 0.016 and p <
      0.001) in endometriosis, while CDH1 expression was concordantly reduced in these
      samples (p < 0.001). Similar to TWIST1, the epithelial expression of MYC was also
      significantly enhanced in ectopic endometrium compared to eutopic tissues (p =
      0.008). We found exclusive expression of either TWIST1 or MYC in the same samples
      (p = 0.003). CONCLUSIONS: Epithelial TWIST1 is overexpressed in endometriosis and
      may contribute to the formation of endometriotic lesions by inducing epithelial
      to mesenchymal transition, as CDH1 was reduced in ectopic lesions. We found
      exclusive expression of either TWIST1 or MYC in the same samples, indicating that
      EMT and proliferation contribute independently of each other to the formation of
      endometriotic lesions.

PMID- 26198058
TI  - MiR-23b and miR-199a impair epithelial-to-mesenchymal transition during
      atrioventricular endocardial cushion formation.
AB  - BACKGROUND: Valve development is a multistep process involving the activation of
      the cardiac endothelium, epithelial-mesenchymal transition (EMT) and the
      progressive alignment and differentiation of distinct mesenchymal cell types.
      Several pathways such as Notch/delta, Tgf-beta and/or Vegf signaling have been
      implicated in crucial steps of valvulogenesis. We have previously demonstrated
      discrete changes in microRNAs expression during cardiogenesis, which are
      predicted to target Bmp- and Tgf-beta signaling. We now analyzed the expression
      profile of 20 candidate microRNAs in atrial, ventricular, and atrioventricular
      canal regions at four different developmental stages. RESULTS: qRT-PCR analyses
      of microRNAs demonstrated a highly dynamic and distinct expression profiles
      within the atrial, ventricular, and atrioventricular canal regions of the
      developing chick heart. miR-23b, miR-199a, and miR-15a displayed increased
      expression during early AVC development whereas others such as miR-130a and miR
      200a display decreased expression levels. Functional analyses of miR-23b, miR
      199a, and miR-15a overexpression led to in vitro EMT blockage. Molecular analyses
      demonstrate that distinct EMT signaling pathways are impaired after microRNA
      expression, including a large subset of EMT-related genes that are predicted to
      be targeted by these microRNAs. CONCLUSIONS: Our data demonstrate that miR-23b
      and miR-199a over-expression can impair atrioventricular EMT.

PMID- 26198059
TI  - Optimism and interventional cardiology.

PMID- 26198060
TI  - Time to consider a STEMI sleepover?: measuring the "value" of an in-house STEMI
      team.
AB  - This study demonstrates that the presence of an in-hospital STEMI team
      significantly reduces D2B times. PCI centers should consider the "value"
      (outcomes relative to cost) of an in-house STEMI team. Larger studies are
      required to assess the cost effectiveness and clinical effectiveness attributable
      to an in-house STEMI team.

PMID- 26198061
TI  - Unusual origin for the right coronary artery: one center's observations on
      diagnosis and treatment.
AB  - Right coronary arteries that originate from the left Sinus of Valsalva and course
      intramurally along the aortic wall in their proximal position are a variant of
      anomalous coronary arteries that can be associated with ischemic symptoms.
      Stenting of the proximal portion of these right coronary arteries along the
      intramural course can improve symptoms in those who clearly have anatomic
      distortion of the proximal artery. Long-term outcomes and durability of this
      approach when applied to symptomatic patients is unknown and future work with
      follow up IVUS is needed. 

PMID- 26198062
TI  - Non-cardiac procedures after DES: an everyday issue awaiting answers.
AB  - Need for non-cardiac surgery is a common event during the follow-up of patients
      treated drug-eluting stenting. The eventual associated risks of complications
      (bleeding and stent thrombosis) are relatively low. Larger clinical studies are
      needed to better delineate the optimal management of this population.

PMID- 26198063
TI  - Which do you prefer, OCT or IVUS?
AB  - OCT has higher resolution than IVUS. This study compared the measurements of
      lumen and stent diameters from IVUS or OCT but the images were chosen by the 11
      observers so that the exact same images were not measured. The standard deviation
      of the measurements is tighter with OCT images. The absolute difference in
      measurements was small. This may be clinically insignificant, but operators may
      feel that it is easier to measure stent size from the OCT images.

PMID- 26198064
TI  - Stent edge dissection: depth of injury and adverse outcome.
AB  - Deep stent edge dissection by OCT predicts adverse outcome. STEMI culprit lesions
      are most susceptible to edge dissection. Procedural performance influences edge
      dissection.

PMID- 26198065
TI  - Drug-coated balloons--the importance of packing and dosing antiproliferative
      drugs.
AB  - Several balloon catheters coated with paclitaxel have been shown to reduce
      restenosis rates in the superficial femoral artery (SFA) revealing a relatively
      wide therapeutic window of effective doses ranging from 2 to 3 ug/mm(2) balloon
      surface area. Delivering lower antiproliferative drug doses to the vessel wall
      may not be inferior to higher drug doses provided that effective drug-excipient
      formulations have been chosen. Leaving non-flow limiting dissection in the SFA
      non-stented might be an option after use of drug-coated balloons.

PMID- 26198066
TI  - Renal frame count: a measure of renal flow that predicts success of renal artery
      stenting in hypertensive patients.
AB  - OBJECTIVES: Renal artery (RA) stenting can improve control of hypertension yet
      predicting clinical response remains difficult. We sought to determine the role
      of the renal frame count (RFC) (number of angiographic frames for contrast to
      reach distal renal parenchyma after initial RA opacification) as a predictor of
      improvement in blood pressure (BP) after RA stenting. METHODS: Renal flow was
      quantified in 68 consecutive patients (age 72.5 +/- 9.1 years, 72% male)
      undergoing RA stenting for refractory hypertension (BP >= 140/90 mm Hg despite
      treatment with two or more antihypertensive medications) by measuring RFC pre-RA
      stenting. Significant renal artery stenosis (RAS) was defined as a stenosis >=
      70% by visual estimation on angiography. Baseline and 6-month follow-up BP was
      recorded. Clinical response was defined by a drop in systolic blood pressure
      (SBP) >10 mm Hg on the same or fewer number of anti-hypertensive medications.
      RESULTS: Patients with RFC > 30 had SBP reduction (43.2 +/- 25.7 mm Hg vs. 30.1
      +/- 31.3 mm Hg, P = 0.067), diastolic blood pressure reduction (9.1 +/- 19.0 vs. 
      0.2 +/- 13.4 mm Hg, P = 0.02), and mean arterial pressure reduction (23.8 +/-
      19.4 vs. 11.8 +/- 16.1 mm Hg, P < 0.001) compared to patients with RFC <= 30.
      Furthermore, baseline RFC >30 was associated with a higher rate of clinical
      response to RA stenting (93.5% vs. 73%, P = 0.027). CONCLUSIONS: RFC can be used
      as a clinical predictor of response to RA stenting. RFC > 30 was associated with
      reduction in BP after RA stenting and was predictive of clinical response. RFC
      provides a useful intraprocedural tool in assessing the severity of RAS and
      predicts the likelihood of clinical response following RA stenting.

PMID- 26198067
TI  - Renal artery stenting: patient selection post-CORAL.
AB  - Randomized trials (RCT) show no meaningful improvement in hypertension control
      with renal artery stenting (RAS) compared to medical therapy alone in patients
      with largely moderate hypertension and intermediate grade stenoses. Observational
      studies of patients with severe hypertension and high-grade stenoses on multiple
      medications report blood pressure improvement after RAS. Angiographic severity of
      renal artery stenosis has poor correlation with functional measures of flow
      impairment. Renal frame count may be a useful simple measure of flow impairment,
      predicting beneficial blood pressure response to RAS. If confirmed in other
      studies, renal frame count > 30 and a combination of predictive clinical factors
      may help guide selection of patients for RAS in contemporary practice.

PMID- 26198068
TI  - Transcatheter aortic valve implantation for bicuspid aortic valve stenosis.
AB  - In Preprocedural CT, patients with BAV have larger aortic annulus perimeters, and
      more calcified valves compared with TAV. In patients with BAV, self-expandable
      valves were under-expand and balloon-expandable valves have a trend toward
      increased rates of postimplantation AR grade. Self-expandable valves have higher
      postprocedural gradient in BAV compared with TAV. 

PMID- 26198069
TI  - An Arabidopsis Plasma Membrane Proton ATPase Modulates JA Signaling and Is
      Exploited by the Pseudomonas syringae Effector Protein AvrB for Stomatal
      Invasion.
AB  - Stomata are natural openings through which many pathogenic bacteria enter plants.
      Successful bacterial pathogens have evolved various virulence factors to promote
      stomatal opening. Here, we show that the Pseudomonas syringae type III effector
      protein AvrB induces stomatal opening and enhances bacterial virulence in a
      manner dependent on RPM1-INTERACTING4 (RIN4), which promotes stomatal opening by
      positively regulating the Arabidopsis plasma membrane H(+)-ATPase (AHA1), which
      is presumed to directly regulate guard cell turgor pressure. In support of a role
      of AHA1 in AvrB-induced stomatal opening, AvrB enhances ATPase activity in
      plants. Unexpectedly, AHA1 promotes the interaction between the jasmonate (JA)
      receptor CORONATINE INSENSITIVE1 (COI1) and JASMONATE ZIM-DOMAIN (JAZ) proteins
      and enhances JA signaling. JA signaling is required for optimum stomatal
      infection in AHA1-active plants. Similarly, AvrB also induces the COI1-JAZ9
      interaction and the degradation of multiple JAZ proteins. AvrB-induced stomatal
      opening and virulence require the canonical JA signaling pathway, which involves
      the COI1 and NAC transcription factors. The findings thus point to a previously
      unknown pathway exploited by P. syringae that acts upstream of COI1 to regulate
      JA signaling and stomatal opening. 

PMID- 26198071
TI  - Correction.

PMID- 26198070
TI  - Phosphorylation of the Plant Immune Regulator RPM1-INTERACTING PROTEIN4 Enhances
      Plant Plasma Membrane H+-ATPase Activity and Inhibits Flagellin-Triggered Immune
      Responses in Arabidopsis.
AB  - The Pseudomonas syringae effector AvrB targets multiple host proteins during
      infection, including the plant immune regulator RPM1-INTERACTING PROTEIN4 (RIN4)
      and RPM1-INDUCED PROTEIN KINASE (RIPK). In the presence of AvrB, RIPK
      phosphorylates RIN4 at Thr-21, Ser-160, and Thr-166, leading to activation of the
      immune receptor RPM1. Here, we investigated the role of RIN4 phosphorylation in
      susceptible Arabidopsis thaliana genotypes. Using circular dichroism
      spectroscopy, we show that RIN4 is a disordered protein and phosphorylation
      affects protein flexibility. RIN4 T21D/S160D/T166D phosphomimetic mutants
      exhibited enhanced disease susceptibility upon surface inoculation with P.
      syringae, wider stomatal apertures, and enhanced plasma membrane H(+)-ATPase
      activity. The plasma membrane H(+)-ATPase AHA1 is highly expressed in guard
      cells, and its activation can induce stomatal opening. The ripk knockout also
      exhibited a strong defect in pathogen-induced stomatal opening. The basal level
      of RIN4 Thr-166 phosphorylation decreased in response to immune perception of
      bacterial flagellin. RIN4 Thr166D lines exhibited reduced flagellin-triggered
      immune responses. Flagellin perception did not lower RIN4 Thr-166 phosphorylation
      in the presence of strong ectopic expression of AvrB. Taken together, these
      results indicate that the AvrB effector targets RIN4 in order to enhance pathogen
      entry on the leaf surface as well as dampen responses to conserved microbial
      features. 

PMID- 26198072
TI  - A Peptide-Network Weaved Nanoplatform with Tumor Microenvironment Responsiveness
      and Deep Tissue Penetration Capability for Cancer Therapy.
AB  - Novel core-shell tumor-penetrating vesicles consisting of a nanovesicle core with
      tumor-penetrating ligands and enzymatically degradable polymeric peptides
      anchored covalently to the core to form a thin polymeric shell are evaluated as
      drug-delivery systems. This delivery platform demonstrates an enhanced
      therapeutic efficacy attributed to the synergistic contributions from matrix
      metalloproteinase (MMP)-responsive drug release as well as improved tumor
      accumulation and penetration in the tumor microenvironment. 

PMID- 26198073
TI  - Dose-dependent testosterone sensitivity of the steroidal passport and GC-C-IRMS
      analysis in relation to the UGT2B17 deletion polymorphism.
AB  - The newly implemented Steroid Module of the Athlete Biological Passport has
      improved doping tests for steroids. A biomarker included in this passport is the
      urinary testosterone glucuronide to epitestosterone glucuronide (T/E) ratio, a
      ratio greatly affected by a deletion polymorphism in UGT2B17. Suspect urine
      doping tests are further analyzed with gas chromatography-combustion-isotope
      ratio mass spectrometry (GC-C-IRMS) to determine the origin of the androgen. In
      this study, we investigated the sensitivity of the steroidal module and the IRMS
      analysis, in subjects administered with three doses of testosterone enanthate
      (500, 250, and 125 mg), in relation to the UGT2B17 polymorphism. All subjects
      carrying the UGT2B17 enzyme reached the traditionally used threshold, a T/E ratio
      of 4, after all three administered doses, whereas none of the subjects devoid of
      this enzyme reached a T/E of 4. On the other hand, using the athlete biological
      passport and IRMS analysis, all three doses could be detected to a high degree of
      sensitivity. The concentrations of all steroids included in the steroidal module
      were dose dependently increased, except for epitestosterone which decreased
      independent of dose. The decrease in epitestosterone was significantly associated
      with circulatory levels of testosterone post dose (rs =0.60 and p=0.007). In
      conclusion, these results demonstrate that administration of a single dose of 125
      500 mg testosterone enanthate could be detected using the athlete biological
      passport, together with IRMS. Since IRMS is sensitive to testosterone doping
      independent of UGT2B17 genotype, also very small changes in the steroidal
      passport should be investigated with IRMS.

PMID- 26198074
TI  - Assessment of Clinical Complete Response After Chemoradiation for Rectal Cancer
      with Digital Rectal Examination, Endoscopy, and MRI: Selection for Organ-Saving
      Treatment.
AB  - BACKGROUND: The response to chemoradiotherapy (CRT) for rectal cancer can be
      assessed by clinical examination, consisting of digital rectal examination (DRE)
      and endoscopy, and by MRI. A high accuracy is required to select complete
      response (CR) for organ-preserving treatment. The aim of this study was to
      evaluate the value of clinical examination (endoscopy with or without biopsy and
      DRE), T2W-MRI, and diffusion-weighted MRI (DWI) for the detection of CR after
      CRT. METHODS: This prospective cohort study in a university hospital recruited 50
      patients who underwent clinical assessment (DRE, endoscopy with or without
      biopsy), T2W-MRI, and DWI at 6-8 weeks after CRT. Confidence levels were used to
      score the likelihood of CR. The reference standard was histopathology or
      recurrence-free interval of >12 months in cases of wait-and-see approaches.
      Diagnostic performance was calculated by area under the receiver operator
      characteristics curve, with corresponding sensitivities and specificities.
      Strategies were assessed and compared by use of likelihood ratios. RESULTS:
      Seventeen (34 %) of 50 patients had a CR. Areas under the curve were 0.88 (0.78
      1.00) for clinical assessment and 0.79 (0.66-0.92) for T2W-MRI and DWI. Combining
      the modalities led to a posttest probability for predicting a CR of 98 %.
      Conversely, when all modalities indicated residual tumor, 15 % of patients still
      experienced CR. CONCLUSIONS: Clinical assessment after CRT is the single most
      accurate modality for identification of CR after CRT. Addition of MRI with DWI
      further improves the diagnostic performance, and the combination can be
      recommended as the optimal strategy for a safe and accurate selection of CR after
      CRT.

PMID- 26198075
TI  - Prognostic Significance of Preoperative Neutrophil-Lymphocyte Ratios in Patients
      with Stage I Non-small Cell Lung Cancer After Complete Resection.
AB  - BACKGROUND: The immune system has been shown to play an important role in
      preventing cancer progression. The neutrophil-lymphocyte ratio (NLR) has been
      proposed to be an indicator of a systemic inflammatory response. We investigated
      the prognostic significance of NLR in patients with completely resected stage I
      non-small lung cancer (NSCLC). METHODS: A series of 343 pathological stage I
      NSCLC patients, completely resected between 2000 and 2008 at a single
      institution, were evaluated retrospectively. Perioperative clinical and
      laboratory data were collected, and the cohort was divided into two groups
      according to preoperative NLR. We examined the correlation between NLR and
      clinicopathological parameters and determined the prognostic significance.
      RESULTS: High NLR was significantly correlated with patients of older age (p =
      0.045), preoperative hypoalbuminemia (p = 0.030), and nonadenocarcinoma histology
      (p = 0.045). Upon univariate analysis, the high NLR group had significantly lower
      5-year recurrence-free survival (81.2 vs. 59.9 %, p < 0.001) and 5-year overall
      survival (89.2 vs. 72.8 %, p < 0.001) than the low NLR group. Multivariate
      analysis showed that NLR was an independent prognostic factor (hazard ratio
      2.141, 95 % confidence interval; 1.306-3.515, p = 0.003). In terms of initial
      recurrent sites, the proportion of patients who developed distant metastasis was
      significantly higher in the high NLR group than in the low NLR group (p < 0.001).
      CONCLUSIONS: Preoperative high NLR is a significant predictor of poor prognosis
      and is associated with more frequent distant metastasis in patients with
      completely resected stage I NSCLC. This readily available and simply calculated
      ratio provides useful information for the clinician to consider in terms of
      perioperative management.

PMID- 26198077
TI  - Flour fortification as a strategy to prevent anaemia.

PMID- 26198076
TI  - The genetic architecture of sexually selected traits in two natural populations
      of Drosophila montana.
AB  - We investigated the genetic architecture of courtship song and cuticular
      hydrocarbon traits in two phygenetically distinct populations of Drosophila
      montana. To study natural variation in these two important traits, we analysed
      within-population crosses among individuals sampled from the wild. Hence, the
      genetic variation analysed should represent that available for natural and sexual
      selection to act upon. In contrast to previous between-population crosses in this
      species, no major quantitative trait loci (QTLs) were detected, perhaps because
      the between-population QTLs were due to fixed differences between the
      populations. Partitioning the trait variation to chromosomes suggested a broadly
      polygenic genetic architecture of within-population variation, although some
      chromosomes explained more variation in one population compared with the other.
      Studies of natural variation provide an important contrast to crosses between
      species or divergent lines, but our analysis highlights recent concerns that
      segregating variation within populations for important quantitative ecological
      traits may largely consist of small effect alleles, difficult to detect with
      studies of moderate power. 

PMID- 26198078
TI  - Ecological connectivity shapes quasispecies structure of RNA viruses in an
      Antarctic lake.
AB  - RNA viruses exist as complex mixtures of genotypes, known as quasispecies, where
      the evolution potential resides in the whole community of related genotypes.
      Quasispecies structure and dynamics have been studied in detail for virus
      infecting animals and plants but remain unexplored for those infecting micro
      organisms in environmental samples. We report the first metagenomic study of RNA
      viruses in an Antarctic lake (Lake Limnopolar, Livingston Island). Similar to low
      latitude aquatic environments, this lake harbours an RNA virome dominated by
      positive single-strand RNA viruses from the order Picornavirales probably
      infecting micro-organisms. Antarctic picorna-like virus 1 (APLV1), one of the
      most abundant viruses in the lake, does not incorporate any mutation in the
      consensus sequence from 2006 to 2010 and shows stable quasispecies with low
      complexity indexes. By contrast, APLV2-APLV3 are detected in the lake water
      exclusively in summer samples and are major constituents of surrounding
      cyanobacterial mats. Their quasispecies exhibit low complexity in cyanobacterial
      mat, but their run-off-mediated transfer to the lake results in a remarkable
      increase of complexity that may reflect the convergence of different viral
      quasispecies from the catchment area or replication in a more diverse host
      community. This is the first example of viral quasispecies from natural aquatic
      ecosystems and points to ecological connectivity as a modulating factor of
      quasispecies complexity. 

PMID- 26198079
TI  - Executive functions in kindergarteners with high levels of disruptive behaviours.
AB  - Executive function (EF) deficits have yet to be demonstrated convincingly in
      children with disruptive behaviour disorders (DBD), as only a few studies have
      reported these. The presence of EF weaknesses in children with DBD has often been
      contested on account of the high comorbidity between DBD and attention
      deficit/hyperactivity disorder (ADHD) and of methodological shortcomings
      regarding EF measures. Against this background, the link between EF and
      disruptive behaviours in kindergarteners was investigated using a carefully
      selected battery of EF measures. Three groups of kindergarteners were compared:
      (1) a group combining high levels of disruptive behaviours and ADHD symptoms
      (COMB); (2) a group presenting high levels of disruptive/aggressive behaviours
      and low levels of ADHD symptoms (AGG); and (3) a normative group (NOR). Children
      in the COMB and AGG groups presented weaker inhibition capacities compared with
      normative peers. Also, only the COMB group showed weaker working memory
      capacities compared with the NOR group. Results support the idea that preschool
      children with DBD have weaker inhibition capacities and that this weakness could
      be common to both ADHD and DBD. 

PMID- 26198080
TI  - Regulation of cell differentiation and function by the euchromatin histone
      methyltranserfases G9a and GLP.
AB  - The euchromatin histone methyltransferases (EHMTs) are an evolutionarily
      conserved protein family that are known for their ability to dimethylate histone
      3 at lysine 9 in euchromatic regions of the genome. In mammals there are two EHMT
      proteins, G9a, encoded by EHMT2, and GLP, encoded by EHMT1. EHMTs have diverse
      roles in the differentiation of different tissues and cell types and are involved
      in adult-specific processes like memory, drug addiction, and immune response.
      This review discusses recent findings from rodent and Drosophila models that are
      beginning to reveal the broad biological role and complex mechanistic functioning
      of EHMT proteins. 

PMID- 26198081
TI  - Parents' Differential Treatment of Adolescent Siblings in African American
      Families.
AB  - Research on European and European American families suggests that parents'
      differential treatment of siblings has negative implications for youths'
      adjustment, but few studies have explored these dynamics in minority samples.
      This study examined parents' differential acceptance and conflict in a sample of
      mothers, fathers, and two adolescent siblings in 179 African American families
      who were interviewed on three annual occasions. In an effort to replicate
      findings from European and European American samples, we assessed the
      longitudinal associations between differential treatment and adolescent
      adjustment and tested three sibling characteristics (birth order, gender, and
      dyad gender composition) as potential moderators of these linkages. To illuminate
      the sociocultural context of differential treatment and its implications, we also
      explored parents' cultural socialization practices and experiences of financial
      stress as potential moderators of these links. Multilevel models revealed that,
      controlling for average parent-child relationship qualities, decreases in
      parental acceptance and increases in parent-youth conflict over time-relative to
      the sibling-were associated with increases in youths' risky behavior and
      depressive symptoms. Links between differential treatment and adjustment were not
      evident, however, when mothers engaged in high levels of cultural socialization
      and in families under high financial stress. The discussion highlights the
      significance of sociocultural factors in family dynamics.

PMID- 26198082
TI  - Streptomycin affinity depends on 13 amino acids forming a loop in homology
      modelled ribosomal S12 protein (rpsL gene) of Lysinibacillus sphaericus DSLS5
      associated with marine sponge (Tedania anhelans).
AB  - Streptomycin, an antibiotic used against microbial infections, inhibits the
      protein synthesis by binding to ribosomal protein S12, encoded by rpsL12 gene,
      and associated mutations cause streptomycin resistance. A streptomycin resistant,
      Lysinibacillus sphaericus DSLS5 (MIC >300 ug/mL for streptomycin), was isolated
      from a marine sponge (Tedania anhelans). The characterisation of rpsL12 gene
      showed a region having similarity to long terminal repeat sequences of murine
      lukemia virus which added 13 amino acids for loop formation in RpsL12; in
      addition, a K56R mutation which corresponds to K43R mutation present in
      streptomycin-resistant Escherichia coli is also present. The RpsL12 protein was
      modelled and compared with that of Lysinibacillus boronitolerans, Escherichia
      coli and Mycobacterium tuberculosis. The modelled proteins docked with
      streptomycin indicate compound had less affinity. The effect of loop on
      streptomycin resistance was analysed by constructing three different models of
      RpsL12 by, (i) removing both loop and mutation, (ii) removing the loop alone
      while retaining the mutation and (iii) without mutation having loop. The results
      showed that the presence of loop causes streptomycin resistance (decreases the
      affinity), and it further enhanced in the presence of mutation at 56th codon.
      Further study will help in understanding the evolution of streptomycin resistance
      in organisms. 

PMID- 26198084
TI  - Fate of Clostridium botulinum and incidence of pathogenic clostridia in biogas
      processes.
AB  - AIMS: This study aimed to assess the sanitary situation in agricultural biogas
      plants (BP) regarding pathogenic Clostridium spp. METHODS AND RESULTS: The
      incidence of Clostridium botulinum, Clostridium difficile, Clostridium novyi,
      Clostridium haemolyticum, Clostridium septicum and Clostridium chauvoei was
      investigated in 154 plant and animal substrates, digester sludges and digestates
      from full-scale BP using a method combining microbial enrichment with Real-Time
      PCR. The investigated clostridia were absent in the samples, except for Cl. novyi
      that was barely present (3.9%) and Cl. difficile that was more frequently
      detected (44.8%). Clostridium botulinum exposed to lab-scale digesters in
      sentinel chambers was reduced with D-values of 34.6 +/- 11.2 days at 38 degrees C
      and 1.0 +/- 0.2 days at 55 degrees C. CONCLUSIONS: These findings indicate minor
      relevance of clostridial pathogens in BP and an improved sanitary quality of the
      digestion product compared to untreated substrates concerning Cl. botulinum.
      However, the frequent detection of Cl. difficile opens questions on the
      durability of this organism in manure digestion lines. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This is the first study providing data on the reduction of Cl.
      botulinum during biogas processes that scientifically invalidate contrary claims
      by some media in the public. Furthermore, the results improve the fragmentary
      knowledge on the prevalence of several clostridial pathogens in agricultural
      biogas production.

PMID- 26198083
TI  - Socio-demographic factors and neighbourhood social cohesion influence adults'
      willingness to grant children greater independent mobility: A cross-sectional
      study.
AB  - BACKGROUND: In developed countries, children's independent mobility levels are
      low. Built environmental factors and parental safety concerns are well-known to
      predict the level of independent mobility adults grant to children. In contrast,
      the influence of adults' socio-demographic characteristics and neighbourhood
      social cohesion on children's independent mobility is largely unexplored. This
      study investigated the influence of adults' socio-demographic factors and
      neighbourhood social cohesion on distances they would permit children for
      independent travel and outdoor play. METHODS: In 2013, a random sample of 1293
      Australian adults (mean age: 56.1 years, 52 % male, 81 % parents) participated in
      the Queensland Social Survey (QSS) via computer-assisted telephone interview.
      Socio-demographic factors measured included age, sex, parental status, education
      and area-level socio-economic disadvantage. Perceived neighbourhood social
      cohesion was assessed using a standardised scale. Adults reported the distances
      children aged 8-12 years should be allowed to walk/cycle to places, and play
      outdoors without adults. Responses were categorised into 'within sight', < 0.5
      kilometres (km) , 0.5-1 km and >1 km. Ordinal logistic regression was used to
      assess associations of socio-demographic factors and neighbourhood social
      cohesion with distances adults would permit for children's independent travel and
      outdoor play. RESULTS: Parents and adults with lower education were less likely
      to permit greater distances for children's independent travel (OR 0.57 and OR =
      0.59, respectively). Women, parents and adults with lower education were less
      likely to grant children greater distances for independent outdoor play (OR =
      0.61, OR = 0.50 and OR = 0.60, respectively). In contrast, adults with higher
      perceptions of neighbourhood social cohesion were more likely to permit children
      greater distances for independent travel (OR = 1.05)and outdoor play (OR = 1.05).
      Adult age and area-level socio-economic disadvantage were not associated with
      distances adults would permit for independent travel and outdoor play.
      CONCLUSIONS: Women, parents (particularly those of younger children), adults with
      lower education and those who perceived neighbourhood social cohesion as being
      lower were less willing to let children independently travel further away from
      home. Interventions to increase children's independent mobility may be more
      effective if targeted to these groups. In addition, increasing neighbourhood
      social cohesion may help increase adults' willingness to grant children greater
      independent mobility.

PMID- 26198085
TI  - Molecular epidemiology and antimicrobial susceptibility of Stenotrophomonas
      maltophilia in a Bulgarian university hospital over a 5-year period (2007-2012).

PMID- 26198087
TI  - What the neighbors say.

PMID- 26198086
TI  - The Use of Lidocaine Containing Cardioplegia in Surgery for Adult Acquired Heart
      Disease.
AB  - BACKGROUND: Del Nido cardioplegia, a crystalloid-based solution with lidocaine as
      a key element, is given as a single dose and has been used successfully in
      congenital cardiac surgery. HYPOTHESIS: We retrospectively compared a lidocaine
      containing "modified del Nido" solution with our standard whole blood
      cardioplegia to investigate its safety and efficacy in adult cardiac surgery.
      METHODS: From June 1, 2013 to December 30, 2013, we used a single dose of
      lidocaine containing cardioplegia (LC group) in 92 consecutive operations.
      Propensity matching analysis was undertaken to compare the outcomes of such
      patients with those who underwent their surgery by the same surgeon using
      standard whole blood cardioplegia (WB group), n = 396. Propensity score matching
      yielded 79 pairs of patients. RESULTS: After propensity matching, LC and WB
      groups were similar in baseline operative characteristics including cross-clamp
      time (LC: 65 minutes [range 54 to 89] vs. WB: 70 minutes [54 to 86], p = 0.993).
      Postoperative outcomes were similar including inotropic requirements (30.4%
      [24/72] vs. 25.3% [20/72], p < 0.60), median ventilation time (4.7 hours vs. 5.3,
      p < 0.74) and median length of stay was seven days for both groups (p < 0.82).
      Despite higher median postoperative, 24-hour CK-MB levels LC group (LC:22.3
      ng/ml, range [15.6 to 40.3] vs. WB:18.4 ng/ml [13.9 to 28.2], p = 0.040),
      operative and one-year mortality were comparable among study groups (both p >
      0.798). CONCLUSIONS: Lidocaine containing cardioplegia appears to be safe in
      adults undergoing cardiac procedure when administered for the first 60 minutes of
      aortic cross clamping. Higher CK-MB levels did not translate into adverse
      clinical outcomes.

PMID- 26198088
TI  - Subcutaneous Mycosis Due to Cladosporium cladosporioides and Bipolaris cynodontis
      from Assam, North-East India and Review of Published Literature.
AB  - A large number of phaeoid fungi cause infection in humans and other animals which
      is characterized by the basic development of sclerotic body, dark-coloured
      filamentous hyphae as well as yeast-like cells in the invaded tissue. Two cases
      of subcutaneous mycosis in immunocompetent male patients aged 55 and 58 years
      attending Dermatology outpatient department of a tertiary care hospital in Assam,
      north-east India, are reported. The first case was diagnosed as
      chromoblastomycosis which was caused by Cladosporium cladosporioides. The patient
      clinically presented with a chronic verrucous and nodular growth of 32-year
      duration on the left foot and leg. Identification of the species was done by
      sequencing the D1/D2 region of LSU (large subunit 28S rDNA). The patient was
      treated with surgical resection and oral itraconazole which showed good clinical
      response and total regression of lesion after 9 months. The second case due to
      Bipolaris cynodontis presented as verrucous exophytic growth over the dorsum of
      the right foot of 1-year duration which was diagnosed as chromoblastomycosis. The
      identification of the species was done by sequencing the ITS region. The patient
      was started with oral itraconazole but was lost to follow-up. Chromoblastomycosis
      due to Cladosporium cladosporioides is rare. Bipolaris cynodontis is not yet
      reported as a cause of human infection. The aetiological role of this fungus was
      confirmed by repeated isolation of the fungus from the lesion and direct
      microscopy. Molecular identification methods can increase the spectrum of black
      moulds causing human infection in coming years. We are reporting these two cases
      with review of the available literature.

PMID- 26198089
TI  - KIR3DS1*0130109: a novel activating three-domain KIR identified using sequence
      based typing.
AB  - KIR3DS1*0130109 is similar to KIR3DS1*0130101 except for a A > G change in intron
      4. 

PMID- 26198090
TI  - Endobronchial angiofibroma in the aberrant tracheal bronchus presenting as
      spontaneous pneumomediastinum.
AB  - BACKGROUND: Spontaneous pneumomediastinum is a self-limiting benign disease but
      abnormal bronchial lesions can be rarely found incidentally, and in selected
      cases will require surgical resection. MATERIALS AND METHODS: A 38-year-old man
      presented with a spontaneous pneumomediastinum. Chest computed tomography
      revealed an incidental linear endobronchial tumour in the aberrant tracheal
      bronchus. The tumour was removed surgically and diagnosed with a rare benign
      tumour of endobronchial angiofibroma. CONCLUSIONS: We report a rare case of
      endobronchial angiofibroma in the aberrant tracheal bronchus which was detected
      during the evaluation of a spontaneous pneumomediastinum.

PMID- 26198091
TI  - Photo-damage, photo-protection and age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a degenerative retinal disease that
      causes blindness in people 60-65 years and older, with the highest prevalence
      appearing in people 90 years-old or more. Epidemiological estimates indicate that
      the number of cases is increasing, and will almost double in the next 20 years.
      Preventive measures require precise etiological knowledge. This is quite
      difficult, since AMD is a multifactorial condition with intricate relationships
      between causes and risk factors. In this review, we describe the impact of light
      on the structure and physiology of the retina and the pigment epithelium, taking
      into account the continuous exposure to natural and artificial light sources
      along the life of an individual. A large body of experimental evidence
      demonstrates the toxic effects of some lighting conditions on the retina and the
      pigment epithelium, and consensus exists about the importance of photo-oxidation
      phenomena in the causality chain between light and retinal damage. Here, we
      analyzed the transmission of light to the retina, and compared the aging human
      macula in healthy and diseased retinas, as shown by histology and non-invasive
      imaging systems. Finally, we have compared the putative retinal photo-sensitive
      molecular structures that might be involved in the genesis of AMD. The
      relationship between these compounds and retinal damage supports the hypothesis
      of light as an important initiating cause of AMD. 

PMID- 26198092
TI  - A novel synthetic strategy for magnetite-type compounds. A combined experimental
      and DFT-computational study.
AB  - The dynamics of the early stage reaction between benzyl alcohol and
      Fe(acetylacetonate)3 is studied by exploiting the Dynamic Reaction Coordinate
      (DRC) approach, at the PBE0/6-31G* level of theory. Analysis of the DRC
      trajectory provides a detailed molecular insight into the catalytic effect
      observed in the acidic reaction environment, compared to the neutral one. The
      presence of an additional proton in the reaction system, meant to simulate an
      acidic reaction environment, dramatically affects the reaction path: both by
      decreasing the activation energy of the complex dissociation and leading to the
      formation of acetone. 

PMID- 26198093
TI  - A strategy for the identification of combinatorial bioactive compounds
      contributing to the holistic effect of herbal medicines.
AB  - It has been well claimed that herbal medicines (HMs) elicit effects via a multi
      compounds and multi-targets synergistic mode. However, it lacks appropriate
      strategies to uncover the combinatory compounds that take effect together and
      contribute to a certain pharmacological effect of an herb as a whole, which
      represents a major bottleneck in providing sound evidence in supporting the
      clinic benefits of HMs. Here, we proposed a strategy to the identification of
      combinatory compounds contributing to the anti-inflammatory activity of
      Cardiotonic Pill (CP). The strategy proposed herein contains four core steps,
      including the identification of bioequivalent combinatorial compounds, chemical
      family classification-based combinatorial screen, interactive mode evaluation,
      and activity contribution index assay. Using this strategy, we have successfully
      identified six compounds in combination responsible for the anti-inflammatory
      effect of CP, whose anti-inflammatory activities were found comparable to that of
      the whole CP. Additionally, these six compounds take effect via an additive mode
      but little synergism. This study, together with our recent work in the
      identification of bioactive equivalent compounds combination, provides a widely
      applicable strategy to the identification of combinatory compounds responsible
      for a certain pharmacological activity of HMs. 

PMID- 26198094
TI  - Stem cell niche as a prognostic factor in leukemia.
AB  - Despite high interests on microenvironmental regulation of leukemic cells, little
      is known for bone marrow (BM) niche in leukemia patients. Our recent study on BMs
      of acute myeloid leukemia (AML) patients showed that the mesenchymal stromal
      cells (MSCs) are altered during leukemic conditions in a clinical course
      dependent manner. Leukemic blasts caused reprogramming of transcriptomes in MSCs
      and remodeling of niche cross-talk, selectively suppressing normal primitive
      hematopoietic cells while supporting leukemogenesis and chemo- resistance.
      Notably, differences in BM stromal remodeling were correlated to heterogeneity in
      subsequent clinical courses of AML, i.e., low numbers of mesenchymal progenitors
      at initial diagnosis were correlated to complete remission for 5-8 years, and
      high contents of mesenchymal progenitor or MSCs correlated to early or late
      relapse, respectively. Thus, stromal remodeling by leukemic cell is an intrinsic
      part of leukemogenesis that can contribute to the clonal dominance of leukemic
      cells over normal hematopoietic cells, and can serve as a biomarker for
      prediction of prognosis.

PMID- 26198095
TI  - An experimental approach to study the function of mitochondria in cardiomyopathy.
AB  - Cardiomyopathy is an inherited or acquired disease of the myocardium, which can
      result in severe ventricular dysfunction. Mitochondrial dysfunction is involved
      in the pathological process of cardiomyopathy. Many dysfunctions in cardiac
      mitochondria are consequences of mutations in nuclear or mitochondrial DNA
      followed by alterations in transcriptional regulation, mitochondrial protein
      function, and mitochondrial dynamics and energetics, presenting with associated
      multisystem mitochondrial disorders. To ensure correct diagnosis and optimal
      management of mitochondrial dysfunction in cardiomyopathy caused by multiple
      pathogenesis, multidisciplinary approaches are required, and to integrate between
      clinical and basic sciences, ideal translational models are needed. In this
      review, we will focus on experimental models to provide insights into basic
      mitochondrial physiology and detailed underlying mechanisms of cardiomyopathy and
      current mitochondria-targeted therapies for cardiomyopathy.

PMID- 26198096
TI  - CILAIR-Based Secretome Analysis of Obese Visceral and Subcutaneous Adipose
      Tissues Reveals Distinctive ECM Remodeling and Inflammation Mediators.
AB  - In the context of obesity, strong evidences support a distinctive pathological
      contribution of adipose tissue depending on its anatomical site of accumulation.
      Therefore, subcutaneous adipose tissue (SAT) has been lately considered
      metabolically benign compared to visceral fat (VAT), whose location is associated
      to the risk of developing cardiovascular disease, insulin resistance, and other
      associated comorbidities. Under the above situation, the chronic local
      inflammation that characterizes obese adipose tissue, has acquired a major role
      on the pathogenesis of obesity. In this work, we have analyzed for the first time
      human obese VAT and SAT secretomes using an improved quantitative proteomic
      approach for the study of tissue secretomes, Comparison of Isotope-Labeled Amino
      acid Incorporation Rates (CILAIR). The use of double isotope-labeling-CILAIR
      approach to analyze VAT and SAT secretomes allowed the identification of location
      specific secreted proteins and its differential secretion. Additionally to the
      very high percentage of identified proteins previously implicated in obesity or
      in its comorbidities, this approach was revealed as a useful tool for the study
      of the obese adipose tissue microenvironment including extracellular matrix (ECM)
      remodeling and inflammatory status. The results herein presented reinforce the
      fact that VAT and SAT depots have distinct features and contribute differentially
      to metabolic disease. 

PMID- 26198097
TI  - Snf1/AMP-activated protein kinase activates Arf3p to promote invasive yeast
      growth via a non-canonical GEF domain.
AB  - Active GTP-bound Arf GTPases promote eukaryotic cell membrane trafficking and
      cytoskeletal remodelling. Arf activation is accelerated by guanine nucleotide
      exchange factors (GEFs) using the critical catalytic glutamate in all known Sec7
      domain sequences. Yeast Arf3p, a homologue of mammalian Arf6, is required for
      yeast invasive responses to glucose depletion. Here we identify Snf1p as a GEF
      that activates Arf3p when energy is limited. SNF1 is the yeast homologue of AMP
      activated protein kinase (AMPK), which is a key regulator of cellular energy
      homeostasis. As activation of Arf3p does not depend on the Snf1p kinase domain,
      assay of regulatory domain fragments yield evidence that the C-terminal
      hydrophobic alpha-helix core of Snf1p is a non-canonical GEF for Arf3p
      activation. Thus, our study reveals a novel mechanism for regulating cellular
      responses to energy deprivation, in particular invasive cell growth, through
      direct Arf activation by Snf1/AMPK. 

PMID- 26198098
TI  - Ligand Efficiency Outperforms pIC50 on Both 2D MLR and 3D CoMFA Models: A Case
      Study on AR Antagonists.
AB  - The concept of ligand efficiency is defined as biological activity in each
      molecular size and is widely accepted throughout the drug design community. Among
      different LE indices, surface efficiency index (SEI) was reported to be the best
      one in support vector machine modeling, much better than the generally and
      traditionally used end-point pIC50. In this study, 2D multiple linear regression
      and 3D comparative molecular field analysis methods are employed to investigate
      the structure-activity relationships of a series of androgen receptor
      antagonists, using pIC50 and SEI as dependent variables to verify the influence
      of using different kinds of end-points. The obtained results suggest that SEI
      outperforms pIC50 on both MLR and CoMFA models with higher stability and
      predictive ability. After analyzing the characteristics of the two dependent
      variables SEI and pIC50, we deduce that the superiority of SEI maybe lie in that
      SEI could reflect the relationship between molecular structures and corresponding
      bioactivities, in nature, better than pIC50. This study indicates that SEI could
      be a more rational parameter to be optimized in the drug discovery process than
      pIC50.

PMID- 26198099
TI  - Kallistatin protects against sepsis-related acute lung injury via inhibiting
      inflammation and apoptosis.
AB  - Kallistatin, an endogenous plasma protein, exhibits pleiotropic properties in
      inhibiting inflammation, oxidative stress and apoptosis, as evidenced in various
      animal models and cultured cells. Here, we demonstrate that kallistatin levels
      were positively correlated with the concentration of total protein in
      bronchoalveolar lavage fluids (BALF) from patients with sepsis-related acute
      respiratory distress syndrome (ARDS), indicating a compensatory mechanism. Lower
      ratio of kallistatin to total protein in BALF showed a significant trend toward
      elevated neutrophil counts (P = 0.002) in BALF and increased mortality (P =
      0.046). In lipopolysaccharide (LPS)-treated mice, expression of human kallistatin
      in lung by gene transfer with human kallistatin-encoding plasmid ameliorated
      acute lung injury (ALI) and reduced cytokine/chemokine levels in BALF. These mice
      exhibited attenuated lung epithelial apoptosis and decreased Fas/FasL expression
      compared to the control mice. Mouse survival was improved by kallistatin gene
      transfer or recombinant human kallistatin treatment after LPS challenge. In LPS
      stimulated A549 human lung epithelial cells, kallistatin attenuated apoptosis,
      down-regulated Fas/FasL signaling, suppressed intracellular reactive oxygen
      species (ROS) and inhibited ROS-mediated NF-kappaB activation and inflammation.
      Furthermore, LPS-induced apoptosis was blocked by antioxidant N-acetylcysteine or
      NF-kappaB inhibitor via down-regulating Fas expression. These findings suggest
      the therapeutic potential of kallistatin for sepsis-related ALI/ARDS. 

PMID- 26198100
TI  - Assessment of the coordination of integrated health service delivery networks by
      the primary health care: COPAS questionnaire validation in the Brazilian context.
AB  - BACKGROUND: Health systems organized as networks and coordinated by the Primary
      Health Care (PHC) may contribute to the improvement of clinical care, sanitary
      conditions, satisfaction of patients and reduction of local budget expenditures.
      The aim of this study was to adapt and validate a questionnaire - COPAS - to
      assess the coordination of Integrated Health Service Delivery Networks by the
      Primary Health Care. METHODS: A cross sectional approach was used. The population
      was pooled from Family Health Strategy healthcare professionals, of the Alfenas
      region (Minas Gerais, Brazil). Data collection was performed from August to
      October 2013. The results were checked for the presence of floor and ceiling
      effects and the internal consistency measured through Cronbach alpha. Construct
      validity was verified through convergent and discriminant values following
      Multitrait-Multimethod (MTMM) analysis. RESULTS: Floor and ceiling effects were
      absent. The internal consistency of the instrument was satisfactory; as was the
      convergent validity, with a few correlations lower then 0.30. The discriminant
      validity values of the majority of items, with respect to their own dimension,
      were found to be higher or significantly higher than their correlations with the
      dimensions to which they did not belong. CONCLUSION: The results showed that the
      COPAS instrument has satisfactory initial psychometric properties and may be used
      by healthcare managers and workers to assess the PHC coordination performance
      within the Integrated Health Service Delivery Network.

PMID- 26198102
TI  - Roary: rapid large-scale prokaryote pan genome analysis.
AB  - A typical prokaryote population sequencing study can now consist of hundreds or
      thousands of isolates. Interrogating these datasets can provide detailed insights
      into the genetic structure of prokaryotic genomes. We introduce Roary, a tool
      that rapidly builds large-scale pan genomes, identifying the core and accessory
      genes. Roary makes construction of the pan genome of thousands of prokaryote
      samples possible on a standard desktop without compromising on the accuracy of
      results. Using a single CPU Roary can produce a pan genome consisting of 1000
      isolates in 4.5 hours using 13 GB of RAM, with further speedups possible using
      multiple processors. AVAILABILITY AND IMPLEMENTATION: Roary is implemented in
      Perl and is freely available under an open source GPLv3 license from
      http://sanger-pathogens.github.io/Roary CONTACT: roary@sanger.ac.uk SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 26198101
TI  - Overexpression of Class III beta-tubulin, Sox2, and nuclear Survivin is
      predictive of taxane resistance in patients with stage III ovarian epithelial
      cancer.
AB  - BACKGROUND: Class III beta-tubulin, Sox2, and Survivin play important roles in
      tumor survival and proliferation. However, the association of these three factors
      with clinicopathological characteristics, chemoresistance, and survival in
      patients with ovarian cancer remains controversial. METHODS: We investigated the
      predictive value and correlation among the expression levels of Class III beta
      tubulin, Sox2, and Survivin in 110 patients with stage III ovarian epithelial
      cancer, including 58 patients who received taxane-based chemotherapy and 52
      patients who received non-taxane-based chemotherapy. Expression of these three
      factors was immunohistochemically examined in 110 ovarian tumor tissues obtained
      from patients before chemotherapy. RESULTS: The positive expression rates for
      Class III beta-tubulin, Sox2, and Survivin in ovarian tumor tissues were 59.09 %,
      61.82 % and 52.73 %, respectively. The expression of nuclear Survivin and Class
      III beta-tubulin was consistent with that of Sox2 (p = 0.005 and 0.020,
      respectively). Positive expression of Class III beta-tubulin, Sox2, and nuclear
      Survivin was significantly associated with chemoresistance to taxane-based
      chemotherapy (p = 0.006, 0.007, and 0.009, respectively), but not to non-taxane
      based chemotherapy. Additionally, overexpression of Class III beta-tubulin, Sox2,
      and nuclear Survivin predicted poor progression-free survival in patients
      receiving taxane-based chemotherapy (p = 0.032, 0.005, and 0.004, respectively).
      CONCLUSIONS: These findings suggest that overexpression of Class III beta
      tubulin, Sox2, and nuclear Survivin might be predictive of taxane resistance and
      poor progression-free survival in patients with stage III ovarian epithelial
      cancer. Expression of these three factors may show positive correlations in these
      patients.

PMID- 26198103
TI  - WATCLUST: a tool for improving the design of drugs based on protein-water
      interactions.
AB  - MOTIVATION: Water molecules are key players for protein folding and function. On
      the protein surface, water is not placed randomly, but display instead a
      particular structure evidenced by the presence of specific water sites (WS).
      These WS can be derived and characterized using explicit water Molecular Dynamics
      simulations, providing useful information for ligand binding prediction and
      design. Here we present WATCLUST, a WS determination and analysis tool running on
      the VMD platform. The tool also allows direct transfer of the WS information to
      Autodock program to perform biased docking. AVAILABILITY AND IMPLEMENTATION: The
      WATCLUST plugin and documentation are freely available at
      http://sbg.qb.fcen.uba.ar/watclust/. CONTACT: marcelo@qi.fcen.uba.ar,
      adrian@qi.fcen.uba.ar.

PMID- 26198104
TI  - Identifying novel associations between small molecules and miRNAs based on
      integrated molecular networks.
AB  - MOTIVATION: miRNAs play crucial roles in human diseases and newly discovered
      could be targeted by small molecule (SM) drug compounds. Thus, the identification
      of small molecule drug compounds (SM) that target dysregulated miRNAs in cancers
      will provide new insight into cancer biology and accelerate drug discovery for
      cancer therapy. RESULTS: In this study, we aimed to develop a novel computational
      method to comprehensively identify associations between SMs and miRNAs. To this
      end, exploiting multiple molecular interaction databases, we first established an
      integrated SM-miRNA association network based on 690 561 SM to SM interactions,
      291 600 miRNA to miRNA associations, as well as 664 known SM to miRNA targeting
      pairs. Then, by performing Random Walk with Restart algorithm on the integrated
      network, we prioritized the miRNAs associated to each of the SMs. By validating
      our results utilizing an independent dataset we obtained an area under the ROC
      curve greater than 0.7. Furthermore, comparisons indicated our integrated
      approach significantly improved the identification performance of those simple
      modeled methods. This computational framework as well as the prioritized SM-miRNA
      targeting relationships will promote the further developments of targeted cancer
      therapies. CONTACT: yxli@sibs.ac.cn, lixia@hrbmu.edu.cn or jiangwei@hrbmu.edu.cn
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 26198105
TI  - The application of a novel 'rising activity, multi-level mixed effects, indicator
      emphasis' (RAMMIE) method for syndromic surveillance in England.
AB  - MOTIVATION: Syndromic surveillance is the real-time collection and interpretation
      of data to allow the early identification of public health threats and their
      impact, enabling public health action. The 'rising activity, multi-level mixed
      effects, indicator emphasis' method was developed to provide a single robust
      method enabling detection of unusual activity across a wide range of syndromes,
      nationally and locally. RESULTS: The method is shown here to have a high
      sensitivity (92%) and specificity (99%) compared to previous methods, whilst
      halving the time taken to detect increased activity to 1.3 days. AVAILABILITY AND
      IMPLEMENTATION: The method has been applied successfully to syndromic
      surveillance systems in England providing realistic models for baseline activity
      and utilizing prioritization rules to ensure a manageable number of 'alarms' each
      day. CONTACT: roger.morbey@phe.gov.uk.

PMID- 26198106
TI  - CEMAsuite: open source degenerate PCR primer design.
AB  - The codon-equivalent multiple alignment suite begins conservational analysis for
      polymerase chain reaction primer design at the protein level, allowing the user
      to design consensus primers capable of detecting homologous coding sequences even
      when low-to-moderate sequence information is available. This package also
      condenses the wealth of information associated with multiple sequence alignments
      and presents them in an intuitive manner, allowing the user to quickly and
      effectively address degenerate primer design considerations. AVAILABILITY AND
      IMPLEMENTATION: https://sourceforge.net/projects/cemasuite/. CONTACT:
      benton@lsu.edu or cemasuite@gmail.com SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 26198108
TI  - Bradyrhizobium subterraneum sp. nov., a symbiotic nitrogen-fixing bacterium from
      root nodules of groundnuts.
AB  - Seven strains of symbiotic bacteria from root nodules of local races of Bambara
      groundnut (Vigna subterranea) and peanuts (Arachis hypogaea) grown on subsistence
      farmers' fields in the Kavango region, Namibia, were previously characterized and
      identified as a novel group within the genus Bradyrhizobium. To corroborate their
      taxonomic status, these strains were further characterized using a polyphasic
      approach. All strains possessed identical 16S rRNA gene sequences with
      Bradyrhizobium yuanmingense CCBAU 10071T being the most closely related type
      strain in the 16S rRNA gene phylogenetic analysis, and Bradyrhizobium daqingense
      CCBAU 15774T in the ITS sequence analysis. Phylogenetic analysis of concatenated
      glnII-recA-rpoB-dnaK placed the strains in a highly supported lineage distinct
      from named species of the genus Bradyrhizobium, most closely related to
      Bradyrhizobium yuanmingense CCBAU 10071T. The species status was validated by
      results of DNA-DNA hybridization. Phylogenetic analysis of nifH genes placed the
      novel strains in a group with nifH of 'Bradyrhizobium arachidis' CCBAU 051107
      that also nodulates peanuts. The combination of phenotypic characteristics from
      several tests including carbon source utilization and antibiotic resistance could
      be used to differentiate representative strains from recognized species of the
      genus Bradyrhizobium. Novel strain 58 2-1T induced effective nodules on V.
      subterranea, Vigna unguiculata and A. hypogaea, and some strains on Lablab
      purpureus. Based on the data presented, we conclude that our strains represent a
      novel species for which the name Bradyrhizobium subterraneum sp. nov. is
      proposed, with 58 2-1T [ = DSM 100298T = LMG 28792T = NTCCM0016T (Windhoek)] as
      the type strain. The DNA G+C content of strain 58 2-1T was 64.7 mol% (T m).

PMID- 26198107
TI  - Complement and macrophage crosstalk during process of angiogenesis in tumor
      progression.
AB  - The complement system, which contains some of the most potent pro-inflammatory
      mediators in the tissue including the anaphylatoxins C3a and C5a are the vital
      parts of innate immunity. Complement activation seems to play a more critical
      role in tumor development, but little attention has been given to the angiogenic
      balance of the activated complement mediators and macrophage polarization during
      tumor progression. The tumor growth mainly supported by the infiltration of M2-
      tumor-associated macrophages, and high levels of C3a and C5a, whereas M1
      macrophages contribute to immune-mediated tumor suppression. Macrophages express
      a cognate receptors for both C3a and C5a on their cell surface, and specific
      binding of C3a and C5a affects the functional modulation and angiogenic
      properties. Activation of complement mediators induce angiogenesis, favors an
      immunosuppressive microenvironment, and activate cancer-associated signaling
      pathways to assist chronic inflammation. In this review manuscript, we
      highlighted the specific roles of complement activation and macrophage
      polarization during uncontrolled angiogenesis in tumor progression, and therefore
      blocking of complement mediators would be an alternative therapeutic option for
      treating cancer.

PMID- 26198109
TI  - Cost analysis of options for management of African Animal Trypanosomiasis using
      interventions targeted at cattle in Tororo District; south-eastern Uganda.
AB  - BACKGROUND: Tsetse-transmitted African trypanosomes cause both nagana (African
      animal Trypanosomiasis-AAT) and sleeping sickness (human African Trypanosomiasis 
      HAT) across Sub-Saharan Africa. Vector control and chemotherapy are the
      contemporary methods of tsetse and trypanosomiasis control in this region. In
      most African countries, including Uganda, veterinary services have been
      decentralised and privatised. As a result, livestock keepers meet the costs of
      most of these services. To be sustainable, AAT control programs need to tailor
      tsetse control to the inelastic budgets of resource-poor small scale farmers. To
      guide the process of tsetse and AAT control toolkit selection, that now, more
      than ever before, needs to optimise resources, the costs of different tsetse and
      trypanosomiasis control options need to be determined. METHODS: A detailed
      costing of the restricted application protocol (RAP) for African trypanosomiasis
      control in Tororo District was undertaken between June 2012 and December 2013. A
      full cost calculation approach was used; including all overheads, delivery costs,
      depreciation and netting out transfer payments to calculate the economic
      (societal) cost of the intervention. Calculations were undertaken in Microsoft
      Excel without incorporating probabilistic elements. RESULTS: The cost of
      delivering RAP to the project was US$ 6.89 per animal per year while that of 4
      doses of a curative trypanocide per animal per year was US$ 5.69. However,
      effective tsetse control does not require the application of RAP to all animals.
      Protecting cattle from trypanosome infections by spraying 25%, 50% or 75% of all
      cattle in a village costs US$ 1.72, 3.45 and 5.17 per animal per year
      respectively. Alternatively, a year of a single dose of curative or prophylactic
      trypanocide treatment plus 50% RAP would cost US$ 4.87 and US$ 5.23 per animal
      per year. Pyrethroid insecticides and trypanocides cost 22.4 and 39.1% of the
      cost of RAP and chemotherapy respectively. CONCLUSIONS: Cost analyses of low cost
      tsetse control options should include full delivery costs since they constitute
      77.6% of all project costs. The relatively low cost of RAP for AAT control and
      its collateral impact on tick control make it an attractive option for livestock
      management by smallholder livestock keepers.

PMID- 26198110
TI  - Metabolomic fingerprinting of saffron by LC/MS: novel authenticity markers.
AB  - An untargeted metabolomic approach using liquid chromatography coupled to
      electrospray ionization time-of-flight mass spectrometry was developed in this
      work to identify novel markers for saffron authenticity which is an important
      matter related to consumer protection, quality assurance, active properties, and
      also economical impact (saffron is the most expensive spice). Metabolic
      fingerprinting of authentic and suspicious saffron samples from different
      geographical origin was obtained and analyzed. Different extracting protocols and
      chromatographic methodologies were evaluated to obtain the most adequate
      extracting and separation conditions. Using an ethanol/water mixture at pH 9.0
      and an elution gradient with a fused core C18 column enabled obtaining the
      highest number of significant components between authentic and adulterated
      saffron. By using multivariate statistical analysis, predictive classification
      models for authenticity and geographical origin were obtained. Moreover, 84 and
      29 significant metabolites were detected as candidates for markers of
      authenticity and geographical origin, respectively, from which only 34
      metabolites were tentatively identified as authenticity markers of saffron, but
      none related to its geographical origin. Six characteristic compounds of saffron
      (kaempferol 3-O-glucoside, kaempferol 3-O-sophoroside, kaempferol 3,7-O
      diglucoside, kaempferol 3,7,4'-O-triglucoside, kaempferol 3-O-sophoroside-7-O
      glucoside, and geranyl-O-glucoside) were confirmed by comparing experimental
      MS/MS fragmentation patterns with those provided in scientific literature being
      proposed as novel markers of authenticity. Graphical Abstract Metabolomic
      fingerprinting of saffron.

PMID- 26198111
TI  - Microarray on digital versatile disc for identification and genotyping of
      Salmonella and Campylobacter in meat products.
AB  - Highly portable, cost-effective, and rapid-response devices are required for the
      subtyping of the most frequent food-borne bacteria; thereby the sample rejection
      strategies and hygienization techniques along the food chain can be tailor
      designed. Here, a novel biosensor is presented for the generic detection of
      Salmonella and Campylobacter and the discrimination between their most prevalent
      serovars (Salmonella Enteritidis, Salmonella Typhimurium) and species
      (Campylobacter jejuni, Campylobacter coli), respectively. The method is based on
      DNA microarray developed on a standard digital versatile disc (DVD) as support
      for a hybridization assay and a DVD driver as scanner. This approach was found to
      be highly sensitive (detection limit down to 0.2 pg of genomic DNA), reproducible
      (relative standard deviation 4-19 %), and high working capacity (20 samples per
      disc). The inclusivity and exclusivity assays indicated that designed
      oligonucleotides (primers and probes) were able to discriminate targeted
      pathogens from other Salmonella serovars, Campylobacter species, or common food
      borne pathogens potentially present in the indigenous microflora. One hundred
      isolates from meat samples, collected in a poultry factory, were analyzed by the
      DVD microarraying and fluorescent real-time PCR. An excellent correlation was
      observed for both generic and specific detection (relative sensitivity 93-99 %
      and relative specificity 93-100 %). Therefore, the developed assay has been shown
      to be a reliable tool to be used in routine food safety analysis, especially in
      settings with limited infrastructure due to the excellent efficiency-cost ratio
      of compact disc technology. Graphical Abstract DNA microarray performed by DVD
      technology for pathogen genotyping. 

PMID- 26198112
TI  - Multi-mycotoxin analysis of animal feed and animal-derived food using LC-MS/MS
      system with timed and highly selective reaction monitoring.
AB  - Mycotoxins have the potential to enter the human food chain through carry-over of
      contaminants from feed into animal-derived products. The objective of the study
      was to develop a reliable and sensitive method for the analysis of 30 mycotoxins
      in animal feed and animal-derived food (meat, edible animal tissues, and milk)
      using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the study,
      three extraction procedures, as well as various cleanup procedures, were
      evaluated to select the most suitable sample preparation procedure for different
      sample matrices. In addition, timed and highly selective reaction monitoring on
      LC-MS/MS was used to filter out isobaric matrix interferences. The performance
      characteristics (linearity, sensitivity, recovery, precision, and specificity) of
      the method were determined according to Commission Decision 2002/657/EC and
      401/2006/EC. The established method was successfully applied to screening of
      mycotoxins in animal feed and animal-derived food. The results indicated that
      mycotoxin contamination in feed directly influenced the presence of mycotoxin in
      animal-derived food. Graphical abstract Multi-mycotoxin analysis of animal feed
      and animal-derived food using LC-MS/MS. 

PMID- 26198113
TI  - Tuberculosis: a disease without boundaries.
AB  - Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis
      (MTB) that usually affects the lungs leading to severe coughing, fever, and chest
      pains. Although current research in the past four years has provided valuable
      insight into TB transmission, diagnosis, and treatment, much remains to be
      discovered to effectively decrease the incidence of and eventually eradicate TB.
      The disease still puts a strain on public health, being only second to HIV/AIDS
      in causing high mortality rates. This review will highlight the history of TB as
      well as provide an overview of the current literature on epidemiology,
      pathogenesis and the immune response, treatment, and control of TB. In this race
      to combat a disease that knows no boundaries, it is necessary to have a
      conceptual and clear understanding of TB overall with the hope of providing
      better treatment through novel and collaborative research and public health
      efforts.

PMID- 26198114
TI  - Transorbital anastomotic pathways between the external and internal carotid
      systems in children affected by intraocular retinoblastoma.
AB  - PURPOSE: It is well known that many anastomoses can join the external carotid
      system and the ophthalmic artery. However, their frequency has never been
      reported. Since they can be relevant for interventional radiologists operating in
      the orbit, we decided to illustrate and determine the frequency of the
      anastomoses that can be found in children. METHODS: A retrospective study of 443
      angiographic procedures (via ophthalmic artery and/or external carotid artery)
      carried out on 97 children affected by intraocular retinoblastoma was made to
      investigate the arterial anatomy of 106 orbits. RESULTS: Anastomoses were
      observed in 44.33 % of orbits. However, their true frequency is likely much
      higher as the rate of visualization increased up to 91.11 % of orbits when the
      angiographic study was extended to the external carotid artery. In order of
      frequency we detected the following anastomoses: lacrimal artery-middle meningeal
      artery, lacrimal artery-anterior deep temporal artery, ophthalmic artery-middle
      meningeal artery, ophthalmic artery-facial artery, supraorbital artery
      superficial temporal artery, supratrochlear artery-superficial temporal artery,
      supraorbital artery-middle meningeal artery, dorsal nasal artery-infraorbital
      artery, supraorbital artery-zygomaticoorbital artery, lacrimal artery
      zygomaticoorbital artery. CONCLUSION: When properly searched, anastomoses between
      the ophthalmic artery and the external carotid artery are almost constant in
      children. Depending on the clinical scenario, they can represent dangers or
      valuable alternative routes for collateral circulations and intraarterial
      chemotherapy.

PMID- 26198115
TI  - Right hepatic artery crossing the common hepatic artery: an unusual blood supply
      to the liver.
AB  - To perform hepatic surgery a precise preoperative and intraoperative study of
      liver vascular supply is mandatory. Detecting vascular variations may have great
      importance on surgical strategy and outcome, and details of anatomy do not
      concern only academical knowledge but become deeply involved in practice. We
      present a case of unusual blood supply to the liver, the common hepatic artery
      was directed to the right liver and a right hepatic artery originating from the
      superior mesenteric artery was directed to the left liver. The right hepatic
      artery crossed the common hepatic artery in the proximal part of the hepatic
      pedicle, anterior to the portal vein. To our knowledge this type of anatomical
      variation has not been described before and it represents a rare finding that has
      to be kept in mind, especially in case of major hepatectomies and more demanding
      splitting liver procedures such as A.L.P.P.S., in situ split, ex situ split and
      living donor liver transplantation. 

PMID- 26198116
TI  - EVAR: Benefits of CEUS for monitoring stent-graft status.
AB  - Endo vascular aortic repair [EVAR] is performed with low peri-operative morbidity
      and mortality rate and short hospital stay. However, EVAR needs a close and
      lifelong imagining surveillance for a timely detection of possible complications
      including endoleaks, graft migration, fractures, and enlargement of aneurysm sac
      size with eventual rupture. Contrast enhanced computed tomography [CTA] is
      actually considered the gold-standard in EVAR follow-up, but it is accompanied
      with radiation burden and renal injury due to the use of contrast media. In the
      last two decades several studies have shown the role of contrast enhanced
      ultrasound [CEUS] in post-EVAR surveillance, with very good diagnostic
      performance, absence of renal impairment, and no radiation, accompanied by low
      costs, in comparison with CTA. In numerous prospective studies and meta-analyses
      the detection and characterization of endoleaks with CEUS is comparable to that
      of CTA imaging. Nowadays, in the EVAR surveillance novel strategies which involve
      CEUS with a central role, are suggested by several authors and applied in many
      institutions. In this review article we will present a comprehensive overview and
      analyses of the literature on the CEUS state-of-art imagining of EVAR follow-up,
      with its technique, findings, diagnostic accuracy, and its role in the follow up
      program.

PMID- 26198118
TI  - Cardiovascular and Renal Outcomes Trials-Is There a Difference?
AB  - There is a general sense that most outcomes trials in patients receiving dialysis
      failed to yield statistically significant benefits, in contrast to many
      cardiovascular (CV) trials in the general population. It is unknown whether
      methodologic reasons caused this discrepancy. We performed a systematic MEDLINE
      search for randomized trials with mortality end points of the 42 compounds most
      commonly used for CV indications. In total, 115 trials were selected for review.
      We further reviewed 9 mortality end point trials in patients receiving dialysis.
      The CV trials in populations not receiving dialysis enrolled from 66 to 33,357
      participants with an average of 4,910; 59% of the trials showed statistically
      significant results. The average hazard ratio (HR) was 0.77, ranging from 0.10 to
      1.65; 10 drugs had >=5 published trials each. In the population receiving
      dialysis, most drugs were studied in single trials; the average number of
      patients was 1,500 with a range of 127 to 3,883. The average HR was 0.77 and
      ranged from 0.06 to 1.30. Only 22% of the trials showed statistically significant
      results. The limitations listed in the general population and dialysis studies
      were similar. In conclusion, no apparent methodologic issues were detected (other
      than sample size) that could justify the lower frequency of randomized trials
      with statistically significant results in patients receiving dialysis. The most
      obvious difference was the paucity of trials with each drug in the dialysis
      cohorts; this lowers the chances of at least 1 trial being successful. 

PMID- 26198119
TI  - DFT analysis into the intermediates of nickel pyridinethiolate catalysed proton
      reduction.
AB  - Nickel pyridine 2-thiolate (Ni(PyS)3(-)) has shown good stability and activity as
      a H2 generation catalyst for use in solar energy storage. The experimentally
      proposed catalytic pathway is explored using DFT calculations. Free energy
      changes along the reaction coordinate, spin states, localization of charge and
      geometry of the intermediates were explored. Calculations were performed using
      Gaussian 09 with a B3P86/6-31+G(d) basis set and a CPCM water solvation model. Of
      particular interest were our findings that the first reduction occurs at the
      nickel rather than through non-innocent ligands and that water coordination is
      not favourable although protonation of the pyridyl nitrogen causes dechelation.
      Sequential and concerted proton coupled electron transfer were considered in the
      formation of the hydride. 

PMID- 26198117
TI  - Breast cancer in very young women (<30 years): Correlation of imaging features
      with clinicopathological features and immunohistochemical subtypes.
AB  - OBJECTIVE: Early diagnosis of breast cancer in very young women (<30 years) is
      challenging and the characteristic imaging findings are not yet fully understood.
      We evaluated the imaging findings of breast cancer in very young women (<30
      years) and to correlate them with clinicopathological features. MATERIAL AND
      METHODS: A total of 50 surgically confirmed breast cancers were included in our
      retrospective study. The medical records were reviewed and the radiological
      features were analyzed according to the new 5th edition of the ACR BI-RADS
      lexicon. RESULTS: The breast cancers in our study population most commonly
      presented as a self-detected mass (74%), T2-3 stage (58%), histological grade III
      (52.3%) and ER-positive (80%) subtype. The most common finding was an irregular
      (87.5%) hyperdense (66.7%) mass with indistinct margins (50%) on mammography and
      an irregular (75.6%) indistinct (57.8%) hypoechoic/heterogeneous (77.8%) mass
      without a posterior acoustic feature (60%) on ultrasonography. MRI revealed an
      irregular shape (63.3%), irregular margins (43.3%), and heterogeneous enhancement
      (60%) with washout kinetics (69.4%). Mammographically, microcalcifications were
      correlated with the HER2-enriched type, and mass-type lesions were correlated
      with triple-negative cancer (p=0.04). An oval/round mass on ultrasound (p=0.005),
      rim enhancement (p=0.004) and intralesional T2 high signal intensity (p=0.04) on
      MRI were associated with the triple-negative type. CONCLUSIONS: On all imaging
      modalities, breast cancer in very young women usually presented as an irregular
      mass, and certain radiological features could be used for predicting the specific
      tumor type.

PMID- 26198120
TI  - Improvement of Fibrinolytic Activity of Bacillus subtilis 168 by Integration of a
      Fibrinolytic Gene into the Chromosome.
AB  - Fibrinolytic enzyme genes (aprE2, aprE176, and aprE179) were introduced into the
      Bacillus subtilis 168 chromosome without any antibiotic resistance gene. An
      integration vector, pDG1662, was used to deliver the genes into the amyE site of
      B. subtilis 168. Integrants, SJ3-5nc, SJ176nc, and SJ179nc, were obtained after
      two successive homologous recombinations. The integration of each fibrinolytic
      gene into the middle of the amyE site was confirmed by phenotypes (Amy(-),
      Spec(S)) and colony PCR results for these strains. The fibrinolytic activities of
      the integrants were higher than that of B. subtilis 168 by at least 3.2-fold when
      grown in LB broth. Cheonggukjang was prepared by inoculating each of B. subtilis
      168, SJ3-5nc, SJ176nc, and SJ179nc, and the fibrinolytic activity of
      cheonggukjang was 4.6 +/- 0.7, 10.8 +/- 0.9, 7.0 +/- 0.6, and 8.0 +/- 0.2 (U/g of
      cheonggukjang), respectively at 72 h. These results showed that construction of
      B. subtilis strains with enhanced fibrinolytic activities is possible by
      integration of a strong fibrinolytic gene via a marker-free manner. 

PMID- 26198121
TI  - Novel Properties for Endoglucanase Acquired by Cell-Surface Display Technique.
AB  - In order to improve the stability of endoglucanase under thermal and acidic
      conditions, the endoglucanase gene was fused to the N-terminus of the
      Saccharomyces cerevisiae pir gene, encoding the cell wall protein PIR. The fusion
      gene was transformed into Pichia pastoris GS115 for expression. A resulting
      strain with high expression and high activity was identified by examining
      resistance to Geneticin 418, Congo red staining, and quantitative analysis of
      enzyme activity. SDS-PAGE analysis revealed that the endoglucanase was
      successfully displayed on the yeast cell surface. The displayed endoglucanase
      (DEG) showed maximum activity towards sodium carboxyl methyl cellulose at
      approximately 275 IU/g cell dry weight. DEG exhibited greater than 60% residual
      activity in the pH range 2.5-8.5, higher than free endoglucanase (FEG), which had
      40% residual activity at the same pH range. The highest tolerated temperature for
      DEG was 70 degrees C, much higher than that of FEG, which was approximately 50
      degrees C. Moreover, DEG showed 91.1% activity at 65 degrees C for 120 min, while
      FEG only kept 77.8% residual activity over the same period. The half-life of DEG
      was 270 min at 65 degrees C, compared with only 150 min for FEG. DEG could be
      used repeatedly at least three times. These results suggest that the DEG has
      broad applications as a yeast whole-cell biocatalyst, due to its novel properties
      of high catalytic efficiency, acid-thermal stabilities, and reusability. 

PMID- 26198122
TI  - Rabbit Hemorrhagic Disease Virus Variant Recombinant VP60 Protein Induces
      Protective Immunogenicity.
AB  - Rabbit hemorrhagic disease virus (RHDV) is highly contagious and often causes
      fatal disease that affects both wild and domestic rabbits of the species
      Oryctolagus cuniculus. A highly pathogenic RHDV variant (RHDVa) has been
      circulation in the Korean rabbit population since 2007 and has a devastating
      effect on the rabbit industry in Korea. A highly pathogenic RHDVa was isolated
      from naturally infected rabbits, and the gene encoding the VP60 protein was
      cloned into a baculovirus transfer vector and expressed in insect cells. The
      hemagglutination titer of the Sf-9 cell lysate infected with recombinant VP60
      baculovirus was 131,072 units/50 MUl and of the supernatant 4,096 units/50 MUl.
      Guinea pigs immunized twice intramuscularly with a trial inactivated RHDVa
      vaccine containing recombinant VP60 contained 2,152 hemagglutination inhibition
      (HI) geometric mean titers. The 8-week-old white rabbits inoculated with one
      vaccine dose were challenged with a lethal RHDVa 21 days later and showed 100%
      survival rates. The recombinant VP60 protein expressed in a baculovirus system
      induced high HI titers in guinea pigs and rendered complete protection, which led
      to the development of a novel inactivated RHDVa vaccine. 

PMID- 26198123
TI  - Optimization of Expression Conditions Enhances Production of Sepiapterin, a
      Precursor for Tetrahydrobiopterin Biosynthesis, in Recombinant Escherichia coli.
AB  - Sepiapterin is a precursor for the synthesis of tetrahydrobiopterin (BH4), which
      is a wellknown cofactor for aromatic amino acid hydroxylation and nitric oxide
      synthesis in higher mammals. In this study, a recombinant Escherichia coli
      BL21(DE3) strain harboring cyanobacterial guanosine 5'-triphosphate
      cyclohydrolase 1 (GCH1) and human 6- pyruvoyltetrahydropterin synthase (PTPS)
      genes was constructed to produce sepiapterin. The optimum conditions for T7
      promoter-driven expression of GCH1 and PTPS were 30 degrees C and 0.1 mM
      isopropyl-beta-D-thioglucopyranoside (IPTG). The maximum sepiapterin
      concentration of 88.1 +/- 2.4 mg/l was obtained in a batch cultivation of the
      recombinant E. coli, corresponding to an 18-fold increase in sepiapterin
      production compared with the control condition (37 degrees C and 1 mM IPTG). 

PMID- 26198124
TI  - Inhibitory Effect of Lactobacillus plantarum Extracts on HT-29 Colon Cancer Cell
      Apoptosis Induced by Staphylococcus aureus and Its Alpha-Toxin.
AB  - Staphylococcus aureus plays an important role in sepsis, septic shock, pneumonia,
      and wound infections. Here, we demonstrate that Lactobacillus plantarum extracts
      inhibited S. aureusinduced cell death of a human epithelial cell line, HT-29. In
      particular, we have shown that S. aureus-induced cell death was abolished by
      neutralization of alpha-toxin, indicating that alpha-toxin is the major mediator
      of S. aureus-induced cell death. DNA fragmentation experiment and caspase assay
      revealed that the S. aureus-induced cell death was apoptosis. L. plantarum
      extracts inhibited the generation of effector caspase-3 and the initiator caspase
      9 in S. aureusor alpha-toxin-induced cell death. Moreover, expression of Bcl-2,
      an anti-apoptotic protein, was activated in L. plantarum extract-treated cells as
      compared with the S. aureus- or alpha-toxintreated only cells. Furthermore, S.
      aureus-induced apoptosis was efficiently inhibited by lipoteichoic acid and
      peptidoglycan of L. plantarum. Together, our results suggest that L. plantarum
      extracts can inhibit the S. aureus-mediated apoptosis, which is associated with
      S. aureus spreading, in intestinal epithelial cells, and may provide a new
      therapeutic reagent to treat bacterial infections. 

PMID- 26198125
TI  - An Environmentally Friendly and Efficient Method for Extraction of PHB Biopolymer
      with Non-Halogenated Solvents.
AB  - The present study developed an efficient and environmentally friendly method for
      recovering polyhydroxybutyrate (PHB) from Cupriavidus necator. Several non
      halogenated solvents were tested and it was found that butyl acetate and ethyl
      acetate are powerful solvents for the biopolymer. Testing was performed to
      examine the effects of temperature (25  degrees C until temperature below solvent
      boiling points) and heating incubation time (0-60 min) on the two solvents. Butyl
      acetate had a higher recovery level (96%) and product purity (up to 99%) than
      ethyl acetate at 103  degrees C and a heating incubation time of 30 min. Under
      these conditions, PHB recorded the highest molecular weight of 1.4 * 10(6)
      compared with the standard procedure (i.e., recovery using chloroform). The
      proposed strategy showed that butyl acetate is a good alternative to halogenated
      solvents such as chloroform for recovery of PHB.

PMID- 26198126
TI  - Differentiation of hand posture to object shape in children with unilateral
      spastic cerebral palsy.
AB  - Quantifying hand-shaping in children with unilateral spastic cerebral palsy
      (USCP) is the first step in understanding hand posture differentiation. To
      quantify this ability and determine how hand posture evolves during reach toward
      various object shapes in children with unilateral spastic cerebral palsy (USCP),
      2 groups of children (10 typically developing, and 10 USCP, ages 6-13) were
      studied in a single-session cross-sectional study. Subjects grasped rectangular,
      concave, and convex objects with each hand. Metacarpal and proximal
      interphalangeal joint finger flexion and finger abduction angles were calculated.
      The extent to which hand posture reflects object shape was calculated using a
      "visuomotor efficiency (VME) index" (a score of 100 reflects perfect
      discrimination between objects). A mixed design ANOVA with repeated measures on
      time was used to compare the VME between groups. Children with USCP demonstrated
      a lower VME than controls in the affected hand, indicating less effective hand
      shaping; p<.01. There was also a difference between groups in the evolution of
      VME throughout reach; p<.01. No difference in hand-shaping in the less affected
      hand in USCP was observed. Analysis of joint angles at contact and VME throughout
      reach demonstrated that children with USCP differentiated their hand posture to
      objects of different shapes, but demonstrated deficits in the timing and
      magnitude of hand-shaping isolated to the affected side. The present study
      suggests it may be important to consider the quality of hand activity using
      quantitative approaches such as VME analyses. Rehabilitation approaches that
      target these deficits to improve joint mobility and motor control are worth
      testing. 

PMID- 26198127
TI  - Elevated insulin-like growth factor 2 expression may contribute to the
      hypermuscular phenotype of myostatin null mice.
AB  - OBJECTIVES: Myostatin (Mstn) inhibits while insulin-like growth factors 1 and 2
      (Igf1 and Igf2) increase skeletal muscle growth. However, there is little known
      regarding Mstn regulation of Igf1 and Igf2 expression. Therefore, the objective
      of this study was to quantify the expression of IGF family members in skeletal
      muscle and liver throughout the growth phase of Mstn null (MN) mice. Further,
      differences between male and female mice were investigated. METHODS: Male and
      female wild type (WT) and MN mice were euthanized at birth (0 d), 7 days (7 d),
      weaning (21 d), sexual maturity (42 d), and 70 d. For the neonatal periods, 0 d
      and 7 d, all muscles from the hind limbs were compiled for RNA extraction. At 21
      d, 42 d, and 70 d, biceps femoris (BF), tibialis anterior, triceps brachii (TB),
      and gastrocnemius-soleus complex were collected. RESULTS: As expected, muscle
      weights were up to 90% greater in MN mice compared with WT mice at 21 d, 42 d and
      70 d. However, Igf1 expression was reduced (P <= 0.04) at 7d and 21 d in MN mice
      compared to WT mice. Expression of Igf2 did not differ between genotypes at 0 d
      and 7d, but, at 21 d, 42 d and 70 d in BF and TB muscles, Igf2 expression was 1.9
      2.9 fold greater (P<0.01) in MN compared to WT mice. Hepatic Igf1 and Igf2 levels
      were minimally affected by genotype; with the exception of a 1.4-fold reduction
      (P=0.04) in Igf1 expression in 21 d MN mice compared with WT mice. Though male
      mice were heavier than females starting at 21 d of age, expression differences in
      Igf1, Igf2, their receptors and binding proteins do not account for growth
      differences. In every case, when expression was different between sexes, female
      expression was increased despite increased growth in male mice. CONCLUSION: This
      study is the first to provide evidence that Mstn may negatively regulate Igf2
      expression to control postnatal skeletal muscle growth, however differences in
      growth between male and female mice are not readily explained by changes in
      expression of Igf family members.

PMID- 26198128
TI  - N2 is not N2 is not N2.

PMID- 26198129
TI  - Gene-enhanced cell therapy for pulmonary arterial hypertension: Knocking at the
      clinical door?

PMID- 26198130
TI  - Giant right atrial hemangioma: Correlation between magnetic resonance imaging and
      histopathologic evaluation.

PMID- 26198132
TI  - Automatic diagnosis of premature ventricular contraction based on Lyapunov
      exponents and LVQ neural network.
AB  - Premature ventricular contraction (PVC) is a common type of abnormal heartbeat.
      Without early diagnosis and proper treatment, PVC may result in serious harms.
      Diagnosis of PVC is of great importance in goal-directed treatment and
      preoperation prognosis. This paper proposes a novel diagnostic method for PVC
      based on Lyapunov exponents of electrocardiogram (ECG) beats. The methodology
      consists of preprocessing, feature extraction and classification integrated into
      the system. PVC beats can be classified and differentiated from other types of
      abnormal heartbeats by analyzing Lyapunov exponents and training a learning
      vector quantization (LVQ) neural network. Our algorithm can obtain a good
      diagnostic result with little features by using single lead ECG data. The
      sensitivity, positive predictability, and the overall accuracy of the automatic
      diagnosis of PVC is 90.26%, 92.31%, and 98.90%, respectively. The effectiveness
      of the new method is validated through extensive tests using data from MIT-BIH
      database. The experimental results show that the proposed method is efficient and
      robust. 

PMID- 26198131
TI  - Investigation of factors affecting hypothermic pelvic tissue cooling using bio
      heat simulation based on MRI-segmented anatomic models.
AB  - This study applied a simulation method to map the temperature distribution based
      on magnetic resonance imaging (MRI) of individual patients, and investigated the
      influence of different pelvic tissue types as well as the choice of thermal
      property parameters on the efficiency of endorectal cooling balloon (ECB). MR
      images of four subjects with different prostate sizes and pelvic tissue
      compositions, including fatty tissue and venous plexus, were analyzed. The MR
      images acquired using endorectal coil provided a realistic geometry of deformed
      prostate that resembled the anatomy in the presence of ECB. A single slice with
      the largest two-dimensional (2D) cross-sectional area of the prostate gland was
      selected for analysis. The rectal wall, prostate gland, peri-rectal fatty tissue,
      peri-prostatic fatty tissue, peri-prostatic venous plexus, and urinary bladder
      were manually segmented. Pennes' bioheat thermal model was used to simulate the
      temperature distribution dynamics, by using an in-house finite element mesh based
      solver written in MATLAB. The results showed that prostate size and periprostatic
      venous plexus were two major factors affecting ECB cooling efficiency. For cases
      with negligible amount of venous plexus and small prostate, the average
      temperature in the prostate and neurovascular bundles could be cooled down to 25 
      degrees C within 30 min. For cases with abundant venous plexus and large
      prostate, the temperature could not reach 25  degrees C at the end of 3 h
      cooling. Large prostate made the cooling difficult to propagate through. The
      impact of fatty tissue on cooling effect was small. The filling of bladder with
      warm urine during the ECB cooling procedure did not affect the temperature in the
      prostate or NVB. In addition to the 2D simulation, in one case a 3D pelvic model
      was constructed for volumetric simulation. It was found that the 2D slice with
      the largest cross-sectional area of prostate had the most abundant venous plexus,
      and was the most difficult slice to cool, thus it may provide a conservative
      prediction of the cooling effect. This feasibility study demonstrated that the
      simulation tool could potentially be used for adjusting the setting of ECB for
      individual patients during hypothermic radical prostatectomy. Further studies
      using MR thermometry are required to validate the in silico results obtained
      using simulation.

PMID- 26198133
TI  - Effects of Different Zinc Species on Cellar Zinc Distribution, Cell Cycle,
      Apoptosis and Viability in MDAMB231 Cells.
AB  - Intracellular metal elements exist in mammalian cells with the concentration
      range from picomoles per litre to micromoles per litre and play a considerable
      role in various biological procedures. Element provided by different species can
      influence the availability and distribution of the element in a cell and could
      lead to different biological effects on the cell's growth and function. Zinc as
      an abundant and widely distributed essential trace element, is involved in
      numerous and relevant physiological functions. Zinc homeostasis in cells, which
      is regulated by metallothioneins, zinc transporter/SLC30A, Zrt-/Irt-like
      proteins/SLC39A and metal-response element-binding transcription factor-1 (MTF
      1), is crucial for normal cellular functioning. In this study, we investigated
      the influences of different zinc species, zinc sulphate, zinc gluconate and
      bacitracin zinc, which represented inorganic, organic and biological zinc
      species, respectively, on cell cycle, viability and apoptosis in MDAMB231 cells.
      It was found that the responses of cell cycle, apoptosis and death to different
      zinc species in MDAMB231 cells are different. Western blot analysis of the
      expression of several key proteins in regulating zinc-related transcription, cell
      cycle, apoptosis, including MTF-1, cyclin B1, cyclin D1, caspase-8 and caspase-9
      in treated cells further confirmed the observed results on cell level. 

PMID- 26198134
TI  - The Role of Calcium in Ameliorating the Oxidative Stress of Fluoride in Rats.
AB  - The present study was carried out to investigate the effects of fluoride toxicity
      on some biochemical, hormonal, and histological parameters of female rats and the
      protective role of calcium against such effects. Adult female albino rats were
      divided into five groups; control group received distilled water for 60 days,
      calcium group received calcium carbonate with dose of 50 mg/kg three times per
      week for 60 days, fluoride group received sodium fluoride with dose of 20 mg/kg
      three times per week for 60 days, calcium + fluoride group received calcium
      carbonate (50 mg/kg) then after 2 h received sodium fluoride (20 mg/kg) three
      times per week for 60 days, and fluoride + calcium group received sodium fluoride
      (20 mg/kg) three times per week for 30 days then received calcium carbonate (50
      mg/kg) three times per week for another 30 days. The results showed that the
      levels of thiobarbituric acid reactive substances, urea, creatinine, alkaline
      phosphatase, triiodothyronine, thyroxine, parathormone, phosphorous, magnesium,
      alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and
      gamma glutamyl transferase were significantly increased in rats treated with
      fluoride while serum estradiol, calcium, and organ glutathione were significantly
      decreased. The histological examination of the femur bone revealed that fluoride
      treatment induced thinning of bone trabeculae with wilding of marrow space,
      demineralization, and loss of trabeculae interconnections. Also, the histological
      examination of hepatic and renal tissues of fluoride-treated rats showed some
      damages in these tissues while administration of calcium carbonate for 30 or 60
      days during fluoride treatment minimized such damages. It could be concluded that
      administration of calcium to female rats can ameliorate the hazardous effects of
      fluoride observed in the biochemical, hormonal, and histological parameters. 

PMID- 26198135
TI  - Salt-Rich Selenium for Prevention and Control Children with Kashin-Beck Disease:
      a Meta-analysis of Community-Based Trial.
AB  - Kashin-Beck disease (KBD) in western China is not well controlled. The objective
      of this study is to evaluate prevention and control children with KBD through a
      meta-analysis of a community-based trial. Web of knowledge, PubMed, Elsevier, the
      Chinese National Knowledge Infrastructure (CNKI), VIP and Wanfang data had been
      electronically searched up to February 2015. Search terms included the trial
      terms "Salt rich selenium" and "Kashin-Beck disease." Eligible studies were
      prospective trials of salt-rich selenium in endemic villages. Data extraction was
      performed by two authors using predefined data fields that also included quality
      evaluation. Of 292 potentially relevant articles initially screened, reporting 11
      community-based trials with a total enrollment of 2652 participants were
      included, from five provinces in China. The pooled odds ratios (OR) and 95 %
      confidence intervals (CI) of primary prevention in healthy children were 0.16 and
      0.08~0.33, respectively. The OR and 95 % CI of clinical improvement in KBD
      children were 6.57 and 3.33~12.93, respectively. The OR of repairing rate of
      metaphysis lesions was 5.53 (95 % CI 2.92~10.47) based on X-ray film, which was
      statistically significantly different in favor of salt-rich selenium. The
      combined standard mean difference (SMD) of selenium content in hair was 2.54 (95
      % CI 1.21~3.87) which was significantly higher in selenium group. Current
      evidence showed that supplement salt-rich selenium was effective in reducing new
      incidence in healthy children and clinical improvement including repairing
      metaphysis lesions instead of repairing distal end of phalanx lesions in KBD
      children. 

PMID- 26198136
TI  - Cellular responses of eastern oysters, Crassostrea virginica, to titanium dioxide
      nanoparticles.
AB  - Because of the continued development and production of a variety of nanomaterials
      and nanoparticles, their uptake and effects on the biota of marine ecosystems
      must be investigated. Filter feeding bivalve molluscs are highly adapted for
      capturing particles from the external environment and readily internalize nano-
      and micro-sized particles through endocytosis, so they are commonly used as
      valuable indicator species for nanoparticle studies. In these studies, adult
      eastern oysters, Crassostrea virginica, were exposed to a range of titanium
      dioxide nanoparticle (TiO2-NP) concentrations (5, 50, 500, and 5000 MUg/L) in
      conjunction with natural sunlight. Isolated hepatopancreas tissues were also
      exposed to the same TiO2-NP concentrations using particles exposed to similar
      light and dark conditions. Dose-dependent decreases in lysosomal stability were
      observed in the adult oyster studies as well as in the isolated tissues, at
      exposures as low as 50 MUg/L. Titanium accumulation in isolated hepatopancreas
      tissue studies was directly correlated to lysosomal destabilization. Based on
      measurements of lipid peroxidation as an indicator of oxidative stress, TiO2-NPs
      toxicity was not related to increased ROS production over the short-term course
      of these exposures. Analysis of particle size using dynamic light scattering
      (DLS) indicated that concentration had a significant impact on agglomeration
      rates, and the small agglomerates as well as individual particles are readily
      processed by oysters. Overall, this study illustrates that low concentrations of
      TiO2-NPs may cause sublethal toxicity on oysters, which might be enhanced under
      natural sunlight conditions. In estuarine environments, where these nanomaterials
      are likely to accumulate, agglomeration rates, interaction with organics, and
      responses to sunlight are critical in determining the extent of their
      bioreactivity and biological impacts. 

PMID- 26198137
TI  - Possible role of birth weight on general and central obesity in Chinese children
      and adolescents: a cross-sectional study.
AB  - PURPOSE: According to the developmental origins of health and disease theory,
      fetal nutrition is associated with obesity and chronic diseases in children and
      adults. However, previous findings regarding the association between birth weight
      and childhood obesity have been inconsistent. The aim of the present study was to
      investigate the relationship between birth weight and childhood obesity in China.
      METHODS: The 16,580 subjects (8477 boys and 8103 girls) aged 7-17 years, who
      participated in this study were recruited from a cross-sectional study in six
      cities in China. Epidemiological data, including birth information, were
      collected through face-to-face interviews, and anthropometric indices were
      measured by trained physicians. Overweight and obese cases were defined using sex
      specific and age-specific 85th and 95th percentile body mass index (BMI) cutoffs
      for Han children and adolescents. Central obesity was defined using sex-specific
      waist-to-height ratio (WHtR) cutoffs (WHtR >=0.48 in boys and WHtR >=0.46 for
      girls). RESULTS: The overall rate of overweight status and obesity was 20.3% in
      the Chinese children and adolescents and that of central obesity was 18.9%.
      Subjects were stratified into eight groups according to weight at birth. J-shaped
      relationships were observed between birth weight and BMI for age Z-score and
      WHtR. After adjusting for confounders such as gender, gestational age, parental
      factors, and dietary factors, the risk of overweight and obese status was still
      higher in the children with higher birth weights than in children with birth
      weights of 3000-3499 g (3500-3999 g: odds ratio [OR] = 1.14, 95% confidence
      interval [CI] = 1.02-1.28; 4000-4499 g: OR = 1.39, 95% CI = 1.19-1.63; and 4500
      4999 g: OR = 1.36, 95% CI = 1.06-1.76). Moderately high birth weight also
      increased the risk of central obesity. Relative to the children with normal birth
      weights (3000-3499 g), the adjusted OR and 95% CI were 1.33 (1.13-1.56) in
      children with birth weights of 4000-4499 g. Children with very low birth weight
      (lower than 1500 g) had the highest risk of central obesity. The adjusted OR was
      2.30 (95% CI: 1.03-5.14) relative to children with birth weights of 3000-3499 g.
      CONCLUSIONS: Birth weight was associated with obesity in Chinese children and
      adolescents. J-shaped relationships were observed between birth weight and BMI
      and WHtR in childhood, and very low birth weight was associated with a mild
      increase in the risk of central obesity in Chinese children and adolescents.

PMID- 26198139
TI  - Quality control in the ART laboratory: matters arising.

PMID- 26198138
TI  - Dexamethasone attenuates the embryotoxic effect of endometriotic peritoneal fluid
      in a murine model.
AB  - PURPOSE: The in vitro fertilization (IVF) pregnancy rate of women with advanced
      stage endometriosis is nearly half that of the general population, suggesting
      incomplete targeting of the pathophysiology underlying endometriosis-associated
      infertility. Compelling evidence highlights inflammation as the etiologic link
      between endometriosis and infertility and a potential target for adjunctive
      treatment. The objective of this study was to examine the effect of dexamethasone
      on murine embryos exposed to human endometriotic peritoneal fluid (PF) using the
      established murine embryo assay model. METHODS: PF was obtained from women with
      and without severe endometriosis. Murine embryos were harvested and randomly
      allocated to five groups of culture media conditions: (1) human tubal fluid
      (HTF), (2) HTF and 10 % PF from women without endometriosis, (3) HTF and 10 % PF
      from women with endometriosis (PF-E), (4) HTF with PF-E and 0.01 mcg/mL
      dexamethasone, and (5) HTF with PF-E and 0.1 mcg/mL dexamethasone. Embryos were
      cultured in standard conditions and evaluated for blastocyst development.
      RESULTS: A total of 266 mouse embryos were cultured. Baseline blastulation rates
      were 63.6 %. The addition of peritoneal fluid from women with endometriosis
      decreased the blastocyst development rate to 38.9 % (P = 0.008). The addition of
      0.1 mcg/mL of dexamethasone to the culture media restored the blastulation rate
      to near baseline levels (61.2 %; P = 0.019). CONCLUSIONS: The results of our in
      vitro study demonstrate the capacity of dexamethasone to mitigate the deleterious
      impact of endometriotic PF on embryo development. If confirmed in vivo,
      dexamethasone may prove a useful adjunct for the treatment of endometriosis
      associated infertility.

PMID- 26198140
TI  - Government plans inquiry that could mean end of NHS free at point of use.

PMID- 26198141
TI  - Protein microarray with horseradish peroxidase chemiluminescence for
      quantification of serum alpha-fetoprotein.
AB  - OBJECTIVES: To develop and evaluate a protein microarray assay with horseradish
      peroxidase (HRP) chemiluminescence for quantification of alpha-fetoprotein (AFP)
      in serum from patients with hepatocellular carcinoma (HCC). METHODS: A protein
      microarray assay for AFP was developed. Serum was collected from patients with
      HCC and healthy control subjects. AFP was quantified using protein microarray and
      enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum AFP concentrations
      determined via protein microarray were positively correlated (r = 0.973) with
      those determined via ELISA in patients with HCC (n = 60) and healthy control
      subjects (n = 30). Protein microarray showed 80% sensitivity and 100% specificity
      for HCC diagnosis. ELISA had 83.3% sensitivity and 100% specificity. Protein
      microarray effectively distinguished between patients with HCC and healthy
      control subjects (area under ROC curve 0.974; 95% CI 0.000, 1.000). CONCLUSION:
      Protein microarray is a rapid, simple and low-cost alternative to ELISA for
      detecting AFP in human serum.

PMID- 26198142
TI  - Local and long-range endogenous resting potential gradients antagonistically
      regulate apoptosis and proliferation in the embryonic CNS.
AB  - Bioelectric signals, particularly transmembrane voltage potentials (Vmem), play
      an important role in large-scale patterning during embryonic development.
      Endogenous bioelectric gradients across tissues function as instructive factors
      during eye, brain, and other morphogenetic processes. An important and still
      poorly-understood aspect is the control of cell behaviors by the voltage states
      of distant cell groups. Here, experimental alteration of endogenous Vmem was
      induced in Xenopus laevis embryos by misexpression of well-characterized ion
      channel mRNAs, a strategy often used to identify functional roles of Vmem
      gradients during embryonic development and regeneration. Immunofluorescence
      analysis (for activated caspase 3 and phosphor-histone H3P) on embryonic sections
      was used to characterize apoptosis and proliferation. Disrupting local
      bioelectric signals (within the developing neural tube region) increased caspase
      3 and decreased H3P in the brain, resulting in brain mispatterning. Disrupting
      remote (ventral, non-neural region) bioelectric signals decreased caspase 3 and
      highly increased H3P within the brain, with normal brain patterning. Disrupting
      both the local and distant bioelectric signals produced antagonistic effects on
      caspase 3 and H3P. Thus, two components of bioelectric signals regulate apoptosis
      proliferation balance within the developing brain and spinal cord: local
      (developing neural tube region) and distant (ventral non-neural region).
      Together, the local and long-range bioelectric signals create a binary control
      system capable of fine-tuning apoptosis and proliferation with the brain and
      spinal cord to achieve correct pattern and size control. Our data suggest a
      roadmap for utilizing bioelectric state as a diagnostic modality and convenient
      intervention parameter for birth defects and degenerative disease states of the
      CNS.

PMID- 26198143
TI  - Selective depolarization of transmembrane potential alters muscle patterning and
      muscle cell localization in Xenopus laevis embryos.
AB  - The correct anatomical placement and precise determination of specific cell types
      is required for the establishment of normal embryonic patterning. Understanding
      these processes is also important for progress in regenerative medicine and
      cancer biology. Transmembrane voltage gradients across embryonic tissues can
      mediate cellular communication to regulate the processes of proliferation,
      migration, and differentiation. Our past work showed that selective
      depolarization of an endogenous instructor cell population in Xenopus laevis in
      vivo induced a melanoma-like phenotype in the absence of genetic damage. Here, we
      use a hypersensitive glycine-gated chloride channel (GlyR) under control of
      tissue-specific promoters to show that instructor cells resident within muscle
      are more effective at triggering the metastatic conversion of ectodermal
      melanocytes than those similar cells within the nervous system. Moreover,
      depolarization of muscle cells results in aberrant muscle patterning and the
      appearance of cells expressing muscle markers within the neural tube, which
      impacts but does not abolish the animals' ability to learn in an associative
      conditioning assay. Taken together, our data reveal new details of long-range
      (non-cell-autonomous) reprogramming of cell behavior via alteration of the
      resting potential of specific embryonic subpopulations. 

PMID- 26198144
TI  - Histone deacetylases 1 and 2 are required for brain development.
AB  - Epigenetic modifications of histones have been implicated in the regulation of
      cell specific expression of genes required for neuronal development. The best
      studied post-translational (epigenetic) modification of histones is the process
      of reversible acetylation. Two types of enzymes - histone acetyltransferases
      (HATs) and histone deacetylases (HDACs) establish and maintain specific patterns
      of histone acetylation in balance, thereby contributing to both transcriptional
      activation and repression of specific sets of genes. Histone deacetylases
      catalyze the removal of acetyl groups from selected lysine residues in the
      conserved tails of core histone proteins and are considered as transcriptional
      corepressors. A significant amount of data implicates HDACs in diverse biological
      processes, including tissue specific developmental program by silencing specific
      growth-inhibitory genes. In line with this, gene disruption studies have shown
      that the class I deacetylases, HDAC1 and HDAC2 play an essential role in nervous
      system development. In the present review, we briefly highlight current insights
      supporting the function of histone deacetylases in rodent brain development and
      discuss present knowledge referring to their role in neurogenesis, taking into
      consideration results obtained in culture systems and in in vivo studies. 

PMID- 26198145
TI  - Conditional pulmonary over-expression of Claudin 6 during embryogenesis delays
      lung morphogenesis.
AB  - Claudin 6 (Cldn6) is a tetraspanin protein expressed by barrier epithelial cells.
      In order to assess the effects of persistent tight junctions involving Cldn6
      during lung development, a doxycycline (dox)-inducible conditional transgenic
      mouse was generated that up-regulates Cldn6 in the distal lung. Pups had
      unlimited access to dox from conception until sacrifice date at embryonic day (E)
      18.5. Quantitative PCR, immunoblotting, and immunohistochemistry revealed
      significantly elevated Cldn6 expression in transgenic mice compared to non
      transgenic controls. There were no differences in terms of lung size, lung
      weight, or whole body weight at the time of necropsy. Histological evaluations
      led to the discovery that E18.5 Cldn6 transgenic pups appeared to be in the early
      canalicular stage of development coincident with fewer, thickened respiratory
      airspaces. In contrast, controls appeared to have entered the saccular stage
      characterized by thin airspace walls and spherical architecture. Immunostaining
      for transcriptional regulators including TTF-1 and FoxA2 was conducted to assess
      cell differentiation and specific cell types were identified via staining for pro
      surfactant protein C (alveolar type II epithelial cells) or Clara Cell Secretory
      Protein (cub or Clara cells). Lastly, cell turnover was qualitatively measured
      via staining for cell proliferation or apoptosis. These data suggest that Cldn6
      is an important junctional protein potentially involved in the programming of
      epithelial cells during lung development. Furthermore, genetic down-regulation of
      Cldn6 as development proceeds may influence differentiation observed in the
      transition from the canalicular to the saccular lung. 

PMID- 26198147
TI  - Whole-genome analysis of an oxacillin-susceptible CC80 mecA-positive
      Staphylococcus aureus clinical isolate: insights into the mechanisms of cryptic
      methicillin resistance.
AB  - OBJECTIVES: The mec and bla systems, among other genetic factors, are critical in
      regulating the expression of methicillin resistance in Staphylococcus aureus. We
      examined by WGS a naturally occurring oxacillin-susceptible mecA-positive S.
      aureus isolate to identify the mechanism conferring oxacillin susceptibility.
      METHODS: The mecA-positive oxacillin-susceptible S. aureus isolate GR2
      (penicillin and oxacillin MICs 0.094 and 1 mg/L, respectively), belonging to
      clonal complex 80, was characterized. DNA fragment libraries were sequenced on
      Roche 454 and Illumina MiSeq sequencers and de novo assembly of the genome was
      generated using SeqMan NGen software. Plasmid curing was conducted by SDS
      treatment. Expression of mecA was quantified without/with beta-lactam pressure.
      RESULTS: The genome of GR2 consisted of a 2 792 802 bp chromosome and plasmids
      pGR2A (28 895 bp) and pGR2B (2473 bp). GR2 carried SCCmec type IV, with a
      truncated/non-functional mecR1 gene and no mecI. A single copy of the bla system,
      with an organization unique for S. aureus, was found, harboured by plasmid pGR2A.
      Particularly, the blaZ gene was orientated like its regulatory genes, blaI and
      blaR1, and a gene encoding transposase IS66 was integrated between blaZ and the
      regulatory genes deleting the 5'-end of blaR1; blaI, encoding blaZ/mecA
      repressor, was intact. After plasmid loss, GR2 became penicillin and oxacillin
      resistant (MICs 0.5 and 6 mg/L, respectively). CONCLUSIONS: We can conclude that
      after exposure to beta-lactams, the non-functional BlaR1 does not cleave the mecA
      repressor BlaI, derepression does not occur and mecA is not efficiently
      expressed. Removal of the bla system after curing of pGR2A allows constitutive
      expression of mecA, resulting in oxacillin and penicillin resistance.

PMID- 26198148
TI  - Noncoding Transcriptional Landscape in Human Aging.
AB  - Aging is a universal phenomenon in metazoans, characterized by a general decline
      of the organism physiology associated with an increased risk of mortality and
      morbidity. Aging of an organism correlates with a decline in function of its
      cells, as shown for muscle, immune, and neuronal cells. As the DNA content of
      most cells within an organism remains largely identical throughout the life span,
      age-associated transcriptional changes must be achieved by epigenetic mechanisms.
      However, how aging may impact on the epigenetic state of cells is only beginning
      to be understood. In light of a growing number of studies demonstrating that
      noncoding RNAs can provide molecular signals that regulate expression of protein
      coding genes and define epigenetic states of cells, we hypothesize that noncoding
      RNAs could play a direct role in inducing age-associated profiles of gene
      expression. In this context, the role of long noncoding RNAs (lncRNAs) as
      regulators of gene expression might be important for the overall transcriptional
      landscape observed in aged human cells. The possible functions of lncRNAs and
      other noncoding RNAs, and their roles in the regulation of aging-related cellular
      pathways will be analyzed. 

PMID- 26198153
TI  - Intraoperative tumor localization and tissue distinction during robotic
      adrenalectomy using indocyanine green fluorescence imaging: a feasibility study.
AB  - BACKGROUND: To investigate the feasibility of a method for intraoperative tumor
      localization and tissue distinction during robotic adrenalectomy (RA) via
      indocyanine green (ICG) imaging under near-infrared light. METHODS: Ten patients
      underwent RA. After exposure of the retroperitoneal space, but before adrenal
      dissection was started, ICG was given intravenously (IV). Fluorescence FireflyTM
      imaging was performed at 1-, 5-, 10-, and 20-min time points. The precision with
      which the borders of the adrenal tissue were distinguished with ICG imaging was
      compared to that with the conventional robotic view. The number and the total
      volume of injections for each patient were recorded. RESULTS: There were six male
      and four female patients. Diagnosis was primary hyperaldosteronism in four
      patients and myelolipoma, adrenocortical neoplasm, adrenocortical hyperplasia,
      Cushing's syndrome, pheochromocytoma, and metastasis in one patient each.
      Procedures were done through a robotic lateral transabdominal approach in nine
      and through a robotic posterior retroperitoneal approach in one patient. Dose per
      injection ranged between 2.5 and 6.3 mg and total dose per patient 7.5-18.8 mg.
      The adrenal gland took up the dye in 1 min, with contrast between adrenal mass
      and surrounding retroperitoneal fat becoming most distinguished at 5 min.
      Fluorescence of adrenal tissue lasted up to 20 min after injection. Overall, ICG
      imaging was felt to help with the conduct of operation in 8 out of 10 procedures.
      There were no conversions to open or morbidity. There were no immediate or
      delayed adverse effects attributable to IV ICG administration. CONCLUSION: In
      this pilot study, we demonstrated the feasibility and safety of ICG imaging in a
      small group of patients undergoing RA. We described a method that enabled an
      effective fluorescence imaging to localize the adrenal glands and guide
      dissection. Future research is necessary to study how this imaging affects
      perioperative outcomes.

PMID- 26198154
TI  - Taxonomy of instructions given to residents in laparoscopic cholecystectomy.
AB  - BACKGROUND: Although simulation-based training allows residents to become
      proficient in surgical skills outside the OR, residents still depend on senior
      surgeons' guidance in transferring skills accumulated from simulators into the
      operating room. This study aimed to identify and classify explicit instructions
      made by attending surgeons to their residents during laparoscopic surgery.
      Through these instructions, we examined the role gaze guidance plays in OR-based
      training. METHODS: A total of ten laparoscopic cholecystectomy cases being
      performed by PGY4 residents were analyzed. The explicit directional instructions
      given by the mentoring attending surgeons to their residents were identified and
      classified into four categories based on their locations in the coordinate
      system. These categories were further combined into two classes, based on the
      target of instructions. The frequencies of instructions in the two classes were
      compared, and effect size was calculated. RESULTS: There were 1984 instructions
      identified in the ten cases. The instructions were categorized into instrument
      guidance (38.51%) and gaze guidance (61.49%). The instrument guidance focused on
      moving the instruments to perform surgical tasks, including directions to
      targets, instrument manipulation, and instrument interaction. The gaze guidance
      focused on achieving common ground during the operation, including target
      identification and target fixation. The frequency of gaze guidance is
      significantly higher than instrument guidance in a laparoscopic cholecystectomy
      (p < 0.001) with a large effect size (r = 0.6). CONCLUSIONS: Gaze guidance has
      become the main focus of OR-based training. The results show a tight connection
      between adopting expert gaze and performing surgical tasks and suggest that gaze
      training should be integrated into the simulation training.

PMID- 26198155
TI  - "See one, do one, teach one": inadequacies of current methods to train surgeons
      in hernia repair.
AB  - INTRODUCTION: Residency/fellowship training in hernia repair is still too widely
      characterized by the "see one, do one, teach one" model. The goal of this study
      was to perform a needs assessment focused on surgical training to guide the
      creation of a curriculum by SAGES intended to improve the care of hernia
      patients. METHODS: Using mixed methods (interviews and online survey), the SAGES
      hernia task force (HTF) conducted a study asking subjects about their perceived
      deficits in resident training to care for hernia patients, preferred training
      topics about hernias, ideal learning modalities, and education development.
      RESULTS: Participants included 18 of 24 HTF members, 27 chief residents and
      fellows, and 31 surgical residents. HTF members agreed that residency exposes
      trainees to a wide spectrum of hernia repairs by a variety of surgeons. They
      cited outdated materials, techniques, and paucity of feedback. Additionally, they
      identified the "see one, do one, teach one" method of training as prevalent and
      clearly inadequate. The topics least addressed were system-based approach to
      hernia care (46 %) and patient outcomes (62 %). Training topics residents
      considered well covered during residency were: preoperative and intraoperative
      decision-making (90 %), complications (94 %), and technical approach for repairs
      (98 %). Instructional methods used in residency include assisted/supervised
      surgery (96 %), Web-based learning (24 %), and simulation (30 %). Residents'
      preferred learning methods included simulation (82 %), Web-based training (61 %),
      hands-on laboratory (54 %), and videos (47 %), in addition to supervised surgery.
      Trainees reported their most desired training topics as basic techniques for
      inguinal and ventral hernia repairs (41 %) versus advanced technical training (68
      %), which mirrored those reported by attending surgeons, 36 % and 71 %,
      respectively. CONCLUSIONS: There was a consensus among HTF members and surgical
      trainees that a comprehensive, dynamic, and flexible educational program
      employing various media to address contemporary key deficits in the care of
      hernia patients would be welcomed by surgeons.

PMID- 26198156
TI  - Comparison of anastomotic configuration after laparoscopic right hemicolectomy
      under enhanced recovery program: side-to-side versus end-to-side anastomosis.
AB  - BACKGROUND: Stapled technique for ileocolic anastomosis is largely supported in
      previous studies. However, standard anastomotic configuration is not conclusive
      and studies are limited. This study aims to compare postoperative outcomes
      between side to side (S-S) and end to side (E-S) stapled anastomosis after
      laparoscopic right hemicolectomy underenhanced recovery program (ERP). METHODS:
      Between October 2009 and November 2012, 89 patients (46 in S-S group, 43 in E-S
      group) who underwent laparoscopic right hemicolectomy for colon cancer and
      managed with ERP were included in the study. Recovery time and cumulative
      recovery rates, the length of hospital stays, complication rates were analyzed to
      compare both configurations. RESULTS: The recovery time were not different
      between groups (S-S group, 135 hours [84-183.5] vs E-S group, 117 hours [94-143];
      P = 0.349). Difference of cumulative recovery rates were observed in
      postoperative day 7 (S-S group, 71.7 % vs E-S group, 93.0 %; P = 0.019). The
      postoperative hospital stay were shorter in E-S group (S-S, 7 days [6-9] vs E-S,
      6 days [5-7]; P = 0.003). The overall complication rates were lower in E-S group
      (26.1 % vs 4.6 %; P = 0.008). Anastomotic leakage was not observed in both
      groups. CONCLUSIONS: E-S configuration after laparoscopic right hemicolectomy
      showed favorable outcomes under enhanced recovery program.

PMID- 26198157
TI  - Basket-in-catheter access for transcystic laparoscopic bile duct exploration:
      technique and results.
AB  - BACKGROUND: When common bile duct (CBD) stones are detected during laparoscopic
      cholecystectomy, the insertion of baskets via the cystic duct (CD) can be
      difficult and may occasionally cause complications. We introduced a new technique
      'basket in catheter' (BIC) for transcystic CBD exploration. METHODS: Although
      cannulating the CD using a cholangiography catheter is successful in most cases,
      it may occasionally be difficult. Cystic duct anatomy may prevent the usually
      stiffer sharper tip of the basket, from entering the CBD, resulting in failure,
      perforation or a false passage. In the majority of our cases, the cholangiography
      catheter (CC) is not withdrawn from the duct should the intraoperative
      cholangiography show CBD stones. The tip of a basket is inserted into the CC and
      advanced to a predetermined distance, allowing the tip of the basket to exit the
      end of the CC into the CBD. The basket is then opened, advanced to feel the lower
      end and manipulated to trap the stone. The common hepatic duct is compressed
      gently to prevent stones from slipping upwards. The catheter and basket are
      pulled back together to extract the stone. RESULTS: We have used this technique
      in 274 cases since 2010. The rate of transcystic versus choledochotomy stone
      extraction has increased, saving unnecessary choledochotomies. The percentage of
      transcystic exploration increased from 55 % for the period 2005-2009 to 70 % for
      the period 2010-2014. There were no conversions to open surgery and no retained
      stones. The morbidity rate was 4.0 % with no mortality. CONCLUSIONS: We
      demonstrate a technique to facilitate the insertion of extraction baskets into
      the common bile duct using the cholangiography catheter as a guide. The 'basket
      in-catheter' (BIC) technique for transcystic CBD exploration is easier and safer
      than inserting the basket alone.

PMID- 26198158
TI  - Morning colonoscopies are associated with improved adenoma detection rates.
AB  - BACKGROUND: Higher adenoma detection rates are associated with decreased risks
      for subsequent colorectal cancers. Studies have suggested that adenoma detection
      rate (ADR) may be affected by timing of colonoscopy due to endoscopist fatigue
      later in the day. The aim of our study is to assess the influence of the timing
      variables on ADR. METHODS: Univariate analysis and multivariate logistic
      regression analysis were performed on a prospective colonoscopy database,
      comparing ADR for colonoscopies performed in the morning shift (AM) and in the
      afternoon shift (PM) over a 1-year period. Each shift lasted 4 h. Only elective
      outpatient completed colonoscopies with adequate bowel preparation, performed by
      four certified staff endoscopists, were included. Surveillance colonoscopies for
      cancers were excluded. ADR was defined as the detection of at least one
      histologically confirmed polyp during colonoscopy. RESULTS: A total of 533
      colonoscopies were included. ADR was 25 % in the cohort. Mean age was 59 (SD
      14.1). Two hundred and seventy (50.6 %) were done in the AM and 263 (49.4 %) were
      done in the PM. ADR was 29 % in the AM group compared to 21 % in the PM group (p
      = 0.03). Excluding time needed for polypectomy, the mean time taken for scope
      withdrawal was significantly longer in the morning group (12 min) compared with
      the afternoon group (10 min) (p = 0.002). The longer withdrawal time in the
      morning was significantly associated with increased ADRs (OR 1.104, 95 % CI 1.063
      1.147) (p < 0.0001). CONCLUSION: Timing of colonoscopy is an independent
      predictor for ADR. Colonoscopies performed in the morning have a longer mean
      withdrawal time, thus leading to a significantly higher ADR. As endoscopists
      concentration decreases as the day progresses, this may account for the shorter
      time spent on colonoscopies on the afternoon.

PMID- 26198159
TI  - Hepatitis E.

PMID- 26198160
TI  - Humeral fractures due to low-energy trauma: an epidemiological survey in patients
      referred to a large emergency department in Northern Italy.
AB  - This survey describes the epidemiology of approximately 1800 low-energy humeral
      fractures seen in a large emergency department in Northern Italy over 7 years
      (2007-2013), highlighting the differences from previous Italian studies. PURPOSE:
      The purpose of this study was to determine the incidence of humeral fractures due
      to low-energy trauma in patients 40 years of age or older referred to a large
      Emergency Department (Parma, Northern Italy) in a 7-year period (2007-2013).
      METHODS: All humeral fractures referred to the emergency department of the
      Academic Hospital of Parma (the main hospital in the province with a catchment
      area of approximately 345,000) were retrieved from the hospital database using
      both ICD-9CM codes and text strings. The diagnosis of humeral fracture due to low
      energy trauma was confirmed by medical records and X-ray reports, after exclusion
      of injuries due to a clear-cut high-energy trauma or cancer. RESULTS: The query
      identified 1843 humeral fractures (1809 first fractures), with a clear
      predominance in women (78 %). Fractures of the proximal humerus represented the
      large majority of humeral fractures (more than 85 %), with an incidence
      progressively increasing with age (more than 60-fold in women and 20-fold in
      men). Simultaneous fractures (hip in particular) were frequent especially after
      85 years of age (1 out of 8 cases). When compared to other Italian studies, the
      incidence of humeral fractures was significantly lower than that derived from
      discharge data corrected for hospitalization rate (standardized rate ratio 0.74;
      p < 0.001), while the pattern of age-related changes was significantly different
      from that computed by applying the ratio between hip and humeral fractures
      observed in Malmo, Sweden, to the Italian hip fracture rates. CONCLUSIONS: This
      study gives an up-to-date description of the epidemiology of low-energy humeral
      fractures in Italy. Our results partly differ from previous Italian studies based
      on indirect estimations.

PMID- 26198162
TI  - Pulmonary Embolism Diagnosed From Right Heart Changes Seen After Exercise Stress
      Echocardiography.

PMID- 26198161
TI  - Risk Stratification in Patients With Aortic Stenosis Using Novel Imaging
      Approaches.

PMID- 26198163
TI  - Extended Monopole antenna Array with individual Shield (EMAS) coil: An improved
      monopole antenna design for brain imaging at 7 tesla MRI.
AB  - PURPOSE: To propose a new Extended Monopole antenna Array with individual Shields
      (EMAS) coil that improves the B1 field coverage and uniformity along the z
      direction. METHODS: To increase the spatial coverage of Monopole antenna Array
      (MA) coil, each monopole antenna was shielded and extended in length. Performance
      of this new coil, which is referred to as EMAS coil, was compared with the
      original MA coil and an Extended Monopole antenna Array coil with no shield
      (EMA). For comparison, flip angle, signal-to-noise ratio (SNR), and receive
      sensitivity maps were measured at multiple regions of interest (ROIs) in the
      brain. RESULTS: The EMAS coil demonstrated substantially larger flip angle and
      receive sensitivity than the MA and EMA coils in the inferior aspect of the
      brain. In the brainstem ROI, for example, the flip angle in the EMAS coil was
      increased by 45.5% (or 60.0%) and the receive sensitivity was increased by 26.9%
      (or 14.9%), resulting in an SNR gain of 84.8% (or 76.3%) when compared with the
      MA coil (or EMA). CONCLUSION: The EMAS coil provided 25.7% (or 24.4%) more
      uniform B1+ field distribution compared with the MA (or EMA) coil in sagittal.
      The EMAS coil successfully extended the imaging volume in lower part of the
      brain. Magn Reson Med 75:2566-2572, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26198164
TI  - Response to Finsterer and Stollberger "Explanations for discordance of
      noncompaction in monozygotic twins".

PMID- 26198165
TI  - Intracarotid Infusion of Mesenchymal Stem Cells in an Animal Model of Parkinson's
      Disease, Focusing on Cell Distribution and Neuroprotective and Behavioral
      Effects.
AB  - Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool
      for Parkinson's disease (PD) and systemic administration of these cells has been
      tested in preclinical and clinical studies. However, no information on survival
      and actual capacity of MSCs to reach the brain has been provided. In this study,
      we evaluated homing of intraarterially infused rat MSCs (rMSCs) in the brain of
      rats bearing a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal
      tract, to establish whether the toxin-induced damage is sufficient to grant MSC
      passage across the blood-brain barrier (BBB) or if a transient BBB disruption is
      necessary. The rMSC distribution in peripheral organs and the effects of cell
      infusion on neurodegenerative process and motor deficits were also investigated.
      rMSCs were infused 14 days after 6-OHDA injection. A hyperosmolar solution of
      mannitol was used to transiently permeabilize the BBB. Behavioral impairment was
      assessed by adjusting step test and response to apomorphine. Animals were
      sacrificed 7 and 28 days after cell infusion. Our work shows that appreciable
      delivery of rMSCs to the brain of 6-OHDA-lesioned animals can be obtained only
      after mannitol pretreatment. A notable percentage of infused cells accumulated in
      peripheral organs. Infusion of rMSCs did not modify the progression of 6-OHDA
      induced damage or the motor impairment at the stepping test, but induced
      progressive normalization of the pathological response (contralateral turning) to
      apomorphine administration. These findings suggest that many aspects should be
      further investigated before considering any translation of MSC systemic
      administration into the clinical setting for PD treatment. SIGNIFICANCE: This
      study demonstrates that mesenchymal stem cells infused through the carotid artery
      do not efficiently cross the blood-brain barrier in rats with a Parkinson's
      disease-like degeneration of nigrostriatal neurons, unless a permeabilizing agent
      (e.g., mannitol) is used. The infusion did not reduce the neuronal damage and
      associated motor impairment, but abolished the motor abnormalities these animals
      typically show when challenged with a dopaminergic agonist. Therefore, although
      arterially infused mesenchymal stem cells did not show neurorestorative effects
      in this study's Parkinson's disease model, they appeared to normalize the
      pathological responsiveness of striatal neurons to dopaminergic stimulation. This
      capability should be further explored in future studies.

PMID- 26198167
TI  - Differential roles for the thyroarytenoid and lateral cricoarytenoid muscles in
      phonation.
AB  - OBJECTIVES/HYPOTHESIS: Laryngeal adductor muscle dysfunction is a common cause of
      voice disorders. Reconstitution of adductor muscle function is often the target
      of therapy, but the effects of these muscles on voice production remain to be
      fully understood. This study investigated the differential roles of
      thyroarytenoid (TA) and lateral cricoarytenoid (LCA) muscles on voice production.
      STUDY DESIGN: Basic science study using an in vivo canine model of phonation.
      METHODS: The TA and LCA muscle nerve branches were stimulated to obtain seven
      graded levels of muscle activation, from threshold to maximal contraction. The
      effects of LCA muscle activation alone, TA muscle activation alone, and combined
      TA and LCA muscle activation on phonation onset parameters were investigated.
      Phonatory posture, phonation onset type, fundamental frequency (F0), phonation
      onset pressure, and airflow were evaluated. RESULTS: LCA muscle activation closed
      the posterior glottis, but the midmembranous gap remained. TA muscle activation
      closed the membranous glottis, but the posterior gap remained. Complete glottal
      closure was obtained only with combined TA and LCA muscle activation. Phonation
      onset with the LCA muscle alone was characterized by multiple modes (soft,
      aperiodic, periodic), whereas with the TA muscle alone it was abrupt and periodic
      but had significant baseline noise. Combined muscle activation led to elimination
      of baseline noise with stable abrupt periodic onset of phonation. Combined muscle
      activation was also necessary for F0 variation. The LCA muscle assisted the TA
      muscle in increasing subglottal pressure while concurrently reducing phonation
      onset airflow. CONCLUSIONS: The TA muscle is necessary for F0 variation, stable
      onset phonation, and increased subglottal pressure, but needs the LCA muscle for
      optimal effectiveness and to reduce airflow requirements with increased
      activation. LEVEL OF EVIDENCE: NA.

PMID- 26198166
TI  - Cell Therapy Using Human Induced Pluripotent Stem Cell-Derived Renal Progenitors
      Ameliorates Acute Kidney Injury in Mice.
AB  - Acute kidney injury (AKI) is defined as a rapid loss of renal function resulting
      from various etiologies, with a mortality rate exceeding 60% among intensive care
      patients. Because conventional treatments have failed to alleviate this
      condition, the development of regenerative therapies using human induced
      pluripotent stem cells (hiPSCs) presents a promising new therapeutic option for
      AKI. We describe our methodology for generating renal progenitors from hiPSCs
      that show potential in ameliorating AKI. We established a multistep
      differentiation protocol for inducing hiPSCs into OSR1+SIX2+ renal progenitors
      capable of reconstituting three-dimensional proximal renal tubule-like structures
      in vitro and in vivo. Moreover, we found that renal subcapsular transplantation
      of hiPSC-derived renal progenitors ameliorated the AKI in mice induced by
      ischemia/reperfusion injury, significantly suppressing the elevation of blood
      urea nitrogen and serum creatinine levels and attenuating histopathological
      changes, such as tubular necrosis, tubule dilatation with casts, and interstitial
      fibrosis. To our knowledge, few reports demonstrating the therapeutic efficacy of
      cell therapy with renal lineage cells generated from hiPSCs have been published.
      Our results suggest that regenerative medicine strategies for kidney diseases
      could be developed using hiPSC-derived renal cells. SIGNIFICANCE: This report is
      the first to demonstrate that the transplantation of renal progenitor cells
      differentiated from human induced pluripotent stem (iPS) cells has therapeutic
      effectiveness in mouse models of acute kidney injury induced by
      ischemia/reperfusion injury. In addition, this report clearly demonstrates that
      the therapeutic benefits come from trophic effects by the renal progenitor cells,
      and it identifies the renoprotective factors secreted by the progenitors. The
      results of this study indicate the feasibility of developing regenerative
      medicine strategy using iPS cells against renal diseases.

PMID- 26198168
TI  - Primary debulking surgery vs. neoadjuvant chemotherapy followed by interval
      debulking surgery for patients with advanced ovarian cancer.
AB  - OBJECTIVES: To compare the survival of patients with stage IIIC or IV epithelial
      ovarian cancer (EOC) who were treated with neoadjuvant chemotherapy (NAC)
      followed by interval debulking surgery (IDS) or primary debulking surgery (PDS),
      and to investigate how to improve the survival of patients with advanced
      epithelial ovarian cancer. METHOD: We retrospectively reviewed 339 patients with
      stage IIIC or IV EOC from January 2005 to December 2010 treated at West China
      Women's and Children's Hospital wherein 114 and 225 patients underwent NAC
      followed by IDS and PDS, respectively. RESULTS: No difference was observed in
      progression-free survival (PFS) or overall survival (OS) between NAC group and
      PDS group (PFS: 11 vs. 10 months, p = 0.629; OS: 25 vs. 25 months, p = 0.992).
      Patients with residual tumors that measured 0.1-1 cm at IDS following NAC had a
      statistically significant lower median OS compared to patients with no residual
      tumor, but comparable to that with residual tumors that measured >1 cm at IDS
      following NAC. The independent predictors of OS are size of residual tumor (p <
      0.001), FIGO stage (p < 0.001), and age (p = 0.003). CONCLUSIONS: NAC followed by
      IDS provides equal survival compared with PDS. Debulking to small residual tumors
      with a maximum diameter of less than 1 cm provides a smaller but still
      significant benefit for patients with PDS but a relatively minor effect with IDS
      following NAC. To improve the survival of patients with advanced ovarian cancer,
      the definition of "optimal" in IDS following NAC should be defined as no residual
      tumor.

PMID- 26198169
TI  - The prognostic of p27(kip1) in ovarian cancer: a meta-analysis.
AB  - PURPOSE: P27(kip1) is a negative cell cycle regulator that plays an important
      role in tumor suppression. Deregulation of p27(kip1) is commonly observed in many
      human cancers. Numerous studies about p27(kip1) are reported in clinical patients
      despite variable data for the prognostic of p27(kip1) expression. Here we report
      a meta-analysis of the association of p27(kip1) expression with the survival of
      ovarian cancer. METHODS: PubMed and Web of science were searched for studies
      evaluating expression of p27(kip1) and prognostic in ovarian cancer. Published
      data were extracted and computed into odds ratios (ORs) for death at 3 and 5
      years. Data were pooled using the random-effect model. All statistical tests were
      two-sided. RESULTS: Analysis included 9 studies: six studies were reported in
      European, three studies were reported in American, and one study was reported in
      Asian. Loss of p27(kip1) was associated with worse overall survival (OS) at both
      3 years [OR = 2.61, 95 % confidence interval (CI) 1.95-3.49, p < 0.05] and 5
      years (OR = 3.01, 95 % CI 2.17-4.17, p < 0.05). Among studies with different
      ethnicity (European, American and Asian), the results showed a more significant
      association in European, including Italy, Germany, and Greece [for both 3-year OS
      (OR = 3.53, 95 % CI 2.37-5.26) and 5-year OS (OR = 3.66, 95 % CI 2.30-5.83)].
      CONCLUSIONS: Loss of p27(kip1) is associated with worse survival in ovarian
      cancer. The development of strategies target p27(kip1) could be a reasonable
      therapeutic approach.

PMID- 26198170
TI  - Kruppel-like factor family genes are expressed during Xenopus embryogenesis and
      involved in germ layer formation and body axis patterning.
AB  - BACKGROUND: Kruppel-like factors (Klfs) are a family of transcription factors
      consisting of 17 members in mammals, Klf1-Klf17, which are involved in
      fundamental cellular physiological procedures, such as cell proliferation,
      differentiation, and apoptosis. However, their functions in embryonic development
      have been poorly understood. Our previous study has demonstrated that the
      pluripotency factor Klf4 participates in germ layer formation and axis patterning
      of Xenopus embryos by means of the regulation of key developmental signals. In
      the present study, we further investigated comprehensively the expression and
      functions of the klf family genes, klf2, klf5, klf6, klf7, klf8, klf11, klf15,
      and klf17, during the embryogenesis of Xenopus laevis. RESULTS: Spatio-temporal
      expression analyses demonstrate that these genes are transcribed both maternally
      and zygotically in Xenopus embryos, and during organogenesis and tissue
      differentiation, they are localized to a variety of placodes and tissues. Gain
      and loss of function studies manifest that Klf factors play different roles in
      germ layer formation and body axis patterning. Moreover, each Klf factor exhibits
      distinct regulatory effects on the expression of genes that are essential for
      germ layer formation and body axis patterning. CONCLUSIONS: These results suggest
      that Klf factors are involved in the fine-tuning of these genes during early
      embryogenesis.

PMID- 26198171
TI  - Endothelial Connexin37 and Connexin40 participate in basal but not agonist
      induced NO release.
AB  - BACKGROUND: Connexin37 (Cx37) and Cx40 are crucial for endothelial cell-cell
      communication and homeostasis. Both connexins interact with endothelial nitric
      oxide synthase (eNOS). The exact contribution of these interactions to the
      regulation of vascular tone is unknown. RESULTS: Cx37 and Cx40 were expressed in
      close proximity to eNOS at cell-cell interfaces of mouse aortic endothelial
      cells. Absence of Cx37 did not affect expression of Cx40 and a 50 % reduction of
      Cx40 in Cx40(+/-) aortas did not affect the expression of Cx37. However, absence
      of Cx40 was associated with reduced expression of Cx37. Basal NO release and the
      sensitivity for ACh were decreased in Cx37(-/-) and Cx40(-/-) aortas but not in
      Cx40(+/-) aortas. Moreover, ACh-induced release of constricting cyclooxygenase
      products was present in WT, Cx40(-/-) and Cx40(+/-) aortas but not in Cx37(-/-)
      aortas. Finally, agonist-induced NO-dependent relaxations and the sensitivity for
      exogenous NO were not affected by genotype. CONCLUSIONS: Cx37 is more markedly
      involved in basal NO release, release of cyclooxygenase products and the
      regulation of the sensitivity for ACh as compared to Cx40.

PMID- 26198172
TI  - Nanocarrier-Integrated Microspheres: Nanogel Tectonic Engineering for Advanced
      Drug-Delivery Systems.
AB  - A nanocarrier-integrated bottom-up method is a promising strategy for advanced
      drug-release systems. Self-assembled nanogels, which are one of the most
      beneficial nanocarriers for drug-delivery systems, are tectonically integrated to
      prepare nanogel-crosslinked (NanoClik) microspheres. NanoClik microspheres
      consisting of nanogel-derived structures (observed by STED microscopy) release
      "drug-loaded nanogels" after hydrolysis, resulting in successful sustained drug
      delivery in vivo. 

PMID- 26198173
TI  - Estimates of tobacco use by wastewater analysis of anabasine and anatabine.
AB  - Wastewater analysis, the chemical analysis of municipal sewage, is fast becoming
      the technique of choice to monitor changes in community consumption of a range of
      compounds over time. Currently wastewater analyses which estimate tobacco
      consumption focus on the major alkaloid nicotine and its urinary metabolite,
      cotinine. As nicotine is also present in replacement therapies such as nicotine
      gum and patches, this analysis is not specific and hence does not truly reflect
      the harmful consumption of tobacco. Two alkaloids - anabasine and anatabine -
      which are specific to dried tobacco, were assessed as biomarkers for tobacco
      consumption in wastewater, together with nicotine and cotinine. Consequently,
      solid phase extraction (SPE) and liquid chromatography-mass spectrometry (LC-MS)
      methods for the detection of anabasine, anatabine, nicotine, and cotinine in
      municipal wastewater were validated. All compounds were detected in wastewater
      extracts and found to have satisfactory recovery, accuracy, precision, and
      stability in wastewater. Daily flow volume and catchment population of the
      wastewater facility were used to estimate normalized consumption figures of
      mg/day/1000 people for composite samples collected over one week, in an
      application of the method. Anabasine and anatabine were found to be suitable
      wastewater biomarkers of tobacco and can be used to assess tobacco consumption of
      communities via wastewater analysis. Application of this methodology can be used
      to collect temporal consumption data which could be used to determine the
      efficacy of tobacco reduction strategies. Copyright (c) 2015 John Wiley & Sons,
      Ltd. 

PMID- 26198174
TI  - Laboratory Evaluation of the gForce TrackerTM, a Head Impact Kinematic Measuring
      Device for Use in Football Helmets.
AB  - This study sought to compare a new head impact-monitoring device, which is not
      limited to specific helmet styles, against reference accelerometer measurements.
      Laboratory controlled impacts were delivered using a linear pneumatic impactor to
      a Hybrid III headform (HIII) fitted with a football helmet and the impact
      monitoring device (gForce Tracker-GFT) affixed to the inside of the helmet.
      Linear regression analyses and absolute mean percent error (MAPE) were used to
      compare the head impact kinematics measured by the GFT to a reference
      accelerometer located at the HIII's center of mass. The coefficients of
      determination were strong for the peak linear acceleration, peak rotational
      velocity, and HIC15 across all impact testing locations (r(2) = 0.82, 0.94, and
      0.70, respectively), but there were large MAPE for the peak linear acceleration
      and HIC15 (MAPE = 49 +/- 21% and 108 +/- 58%). The raw GFT was accurate at
      measuring the peak rotational velocity at the center of mass of the HIII (MAPE =
      9%). Results from the impact testing were used to develop a correction algorithm.
      The coefficients of determination for all impact parameters improved using the
      correction algorithm for the GFT (r(2) > 0.97), and the MAPE were less than 14%.
      The GFT appears to be a suitable impact-monitoring device that is not limited to
      specific styles of football helmets, however, correction algorithms will need to
      be developed for each helmet style.

PMID- 26198175
TI  - Consensus statement for diagnosis  of subcortical small vessel disease.
AB  - Vascular cognitive impairment (VCI) is the diagnostic term used to describe a
      heterogeneous group of sporadic and hereditary diseases of the large and small
      blood vessels. Subcortical small vessel disease (SVD) leads to lacunar infarcts
      and progressive damage to the white matter. Patients with progressive damage to
      the white matter, referred to as Binswanger's disease (BD), constitute a spectrum
      from pure vascular disease to a mixture with neurodegenerative changes.
      Binswanger's disease patients are a relatively homogeneous subgroup with hypoxic
      hypoperfusion, lacunar infarcts, and inflammation that act synergistically to
      disrupt the blood-brain barrier (BBB) and break down myelin. Identification of
      this subgroup can be facilitated by multimodal disease markers obtained from
      clinical, cerebrospinal fluid, neuropsychological, and imaging studies. This
      consensus statement identifies a potential set of biomarkers based on underlying
      pathologic changes that could facilitate diagnosis and aid patient selection for
      future collaborative treatment trials.

PMID- 26198176
TI  - Measurement of Bmax and Kd with the glycine transporter 1 radiotracer 18F-MK6577
      using a novel multi-infusion paradigm.
AB  - Glycine is a co-agonist of glutamate at the NMDA receptor. Glycine transporter 1
      (GlyT1) inhibitors are reported to be potential therapeutic agents for
      schizophrenia. (18)F-MK6577 is a new positron emission tomography (PET)
      radiotracer useful for imaging brain GlyT1 and its occupancy in humans. We
      devised a novel multi-infusion paradigm of radiolabeled and unlabeled compound
      and an iterative linear/nonlinear alternating fitting method to allow for the
      determination of in vivo affinity (Kd) and target concentration (Bmax) images,
      constraining Kd to be uniform across the brain. This paradigm was tested with
      (18)F-MK6577 in baboons. Voxel-based analysis produced high quality Bmax images
      and reliable Kd estimates, and also suggested that the nondisplaceable
      distribution volume (VND) is not uniform throughout the brain. In vivo GlyT1 Kd
      was estimated to be 1.87 nmol/L for (18)F-MK6577, and the rank order of GlyT1
      distribution measured in the baboon brain was: high in the brainstem (133
      nmol/L), medium in the cerebellum (83 nmol/L), and low in the cortex (30 nmol/L).
      These in vivo Kd and Bmax values agreed well with those determined in vitro, thus
      validating our novel multi-infusion approach. 

PMID- 26198177
TI  - Cathepsin L acutely alters microvessel integrity within the neurovascular unit
      during focal cerebral ischemia.
AB  - During focal cerebral ischemia, the degradation of microvessel basal lamina
      matrix occurs acutely and is associated with edema formation and microhemorrhage.
      These events have been attributed to matrix metalloproteinases (MMPs). However,
      both known protease generation and ligand specificities suggest other
      participants. Using cerebral tissues from a non-human primate focal ischemia
      model and primary murine brain endothelial cells, astrocytes, and microglia in
      culture, the effects of active cathepsin L have been defined. Within 2 hours of
      ischemia onset cathepsin L, but not cathepsin B, activity appears in the ischemic
      core, around microvessels, within regions of neuron injury and cathepsin L
      expression. In in vitro studies, cathepsin L activity is generated during
      experimental ischemia in microglia, but not astrocytes or endothelial cells. In
      the acidic ischemic core, cathepsin L release is significantly increased with
      time. A novel ex vivo assay showed that cathepsin L released from microglia
      during ischemia degrades microvessel matrix, and interacts with MMP activity.
      Hence, the loss of microvessel matrix during ischemia is explained by microglial
      cathepsin L release in the acidic core during injury evolution. The roles of
      cathepsin L and its interactions with specific MMP activities during ischemia are
      relevant to strategies to reduce microvessel injury and hemorrhage. 

PMID- 26198178
TI  - Induction of autophagy through the activating transcription factor 4 (ATF4)
      dependent amino acid response pathway in maternal skeletal muscle may function as
      the molecular memory in response to gestational protein restriction to alert
      offspring to maternal nutrition.
AB  - The aim of the present study was to investigate the mechanistic basis of protein
      deficiency during pregnancy in mother that is transduced to offspring. To this
      end, timed-pregnant Sprague-Dawley rats were fed either a control (20 % of energy
      from protein) or low-protein (LP, 8 % of energy from protein) diet during
      gestation. Tissues were collected after delivery from rat dams, and skeletal
      muscle was collected at postnatal day 38 from the offspring. Quantitative RT-PCR
      and Western blot analyses were performed to determine mRNA and protein levels.
      Histological analysis was performed to evaluate myofibre size. LP dams gained
      significantly less weight during pregnancy, developed muscle atrophy, and had
      significantly lower circulating threonine and histidine levels than control dams.
      The mRNA expression of the well-known amino acid response (AAR) pathway-related
      target genes was increased only in the skeletal muscle of LP dams, as well as the
      protein expression levels of activating transcription factor 4 (ATF4) and
      phosphorylated eukaryotic translation initiation factor 2alpha (p-eIF2alpha). The
      mRNA expression of autophagy-related genes was significantly increased in the
      skeletal muscle of LP dams. Moreover, the mRNA expression of genes involved in
      both AAR and autophagy pathways remained elevated and was memorised in the muscle
      of LP offspring that consumed a post-weaning control diet. Additionally, the LP
      diet increased an autophagy marker, microtubule-associated proteins 1A/1B light
      chain 3B (LC3B) protein expression in the skeletal muscle of rat dams, consistent
      with the initiation of autophagy. The LP diet further increased ATF4 binding at
      the predicted regions of AAR and autophagy pathway-related genes. Increased
      binding of ATF4 unveils the crucial role of ATF4 in the activation of autophagy
      in response to protein restriction. Our data suggest that molecular changes in
      maternal muscle are memorised in the offspring long after gestational protein
      restriction, reinforcing the role of maternal signalling in programming offspring
      health.

PMID- 26198182
TI  - Quality of life following ileoanal pouch failure.
AB  - This article describes a novel qualitative study exploring the lived experience
      of participants having undergone ileoanal pouch failure, on a background of
      ulcerative colitis (UC). It focuses on the impact of living with indefinite
      diversion of the pouch and a permanent end ileostomy. Six participants were
      interviewed with an aim to establish their experience of pouch failure and the
      support they required. Five pertinent themes emerged that suggested participants
      did not expect pouch failure and were unprepared for the regression towards UC.
      Some participants recommenced drug therapy, wore pads to manage leakage from the
      diverted pouch, avoided certain social settings or manipulated diet and lifestyle
      in order to gain an acceptable quality of life with a permanent ileostomy. Pouch
      failure potentially presents adverse effects on patients' quality of life, but
      currently there is a deficit in support and resources available in order to
      provide acceptable outcomes for patients experiencing pouch failure. 

PMID- 26198179
TI  - Evolutionary history inferred from the de novo assembly of a nonmodel organism,
      the blue-eyed black lemur.
AB  - Lemurs, the living primates most distantly related to humans, demonstrate
      incredible diversity in behaviour, life history patterns and adaptive traits.
      Although many lemur species are endangered within their native Madagascar, there
      is no high-quality genome assembly from this taxon, limiting population and
      conservation genetic studies. One critically endangered lemur is the blue-eyed
      black lemur Eulemur flavifrons. This species is fixed for blue irises, a
      convergent trait that evolved at least four times in primates and was subject to
      positive selection in humans, where 5' regulatory variation of OCA2 explains most
      of the brown/blue eye colour differences. We built a de novo genome assembly for
      E. flavifrons, providing the most complete lemur genome to date, and a high
      confidence consensus sequence for close sister species E. macaco, the (brown
      eyed) black lemur. From diversity and divergence patterns across the genomes, we
      estimated a recent split time of the two species (160 Kya) and temporal
      fluctuations in effective population sizes that accord with known environmental
      changes. By looking for regions of unusually low diversity, we identified
      potential signals of directional selection in E. flavifrons at MITF, a melanocyte
      development gene that regulates OCA2 and has previously been associated with
      variation in human iris colour, as well as at several other genes involved in
      melanin biosynthesis in mammals. Our study thus illustrates how whole-genome
      sequencing of a few individuals can illuminate the demographic and selection
      history of nonmodel species. 

PMID- 26198183
TI  - Convex stoma appliances: are we getting it right?

PMID- 26198180
TI  - Microbiome changes associated with sustained eradication of Clostridium difficile
      after single faecal microbiota transplantation in children with and without
      inflammatory bowel disease.
AB  - BACKGROUND: Little data are available regarding the effectiveness and associated
      microbiome changes of faecal microbiota transplantation (FMT) for Clostridium
      difficile infection (CDI) in children, especially in those with inflammatory
      bowel disease (IBD) with presumed underlying dysbiosis. AIM: To investigate C.
      difficile eradication and microbiome changes with FMT in children with and
      without IBD. METHODS: Children with a history of recurrent CDI (>=3 recurrences)
      underwent FMT via colonoscopy. Stool samples were collected pre-FMT and post-FMT
      at 2-10 weeks, 10-20 weeks and 6 months. The v4 hypervariable region of the 16S
      rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was
      performed. RESULTS: Eight children underwent FMT for CDI; five had IBD. All had
      resolution of CDI symptoms. All tested had eradication of C. difficile at 10-20
      weeks and 6 months post-FMT. Pre-FMT patient samples had significantly decreased
      bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02)
      and without IBD (P = 0.01). Post-FMT, bacterial diversity in patients increased.
      Six months post-FMT, there was no significant difference between bacterial
      diversity of donors and patients without IBD; however, bacterial diversity in
      those with IBD returned to pre-FMT baseline. Microbiome composition at 6 months
      in IBD-negative patients more closely approximated donor composition compared to
      IBD-positive patients. CONCLUSIONS: FMT gives sustained C. difficile eradication
      in children with and without IBD. FMT-restored diversity is sustained in children
      without IBD. In those with IBD, bacterial diversity returns to pre-FMT baseline
      by 6 months, suggesting IBD host-related mechanisms modify faecal microbiome
      diversity.

PMID- 26198184
TI  - Patients' experiences of pancaking while living with a colostomy: a survey.
AB  - Anecdotally, pancaking is recognised as troublesome within stoma care, leaving
      many people with ostomies feeling exasperated in trying to deal with this
      difficult problem. Stoma care nurses offer strategies to help alleviate it, but
      when strategies fail and appliances continue to leak, or require changing owing
      to risk of leaking, individuals often feel helpless, demoralised and quality of
      life can be damaged. A postal survey was carried out to try and identify some of
      the issues relating to pancaking. Eighty two percent of respondents were likely
      to experience some degree of pancaking and an alarming 58% changed their pouch
      more often as a management technique. Therefore, as a consequence of pancaking,
      the health economy is affected because each individual who suffers from pancaking
      uses a higher number of appliances. This results in increased costs for the NHS.
      There is currently no published research regarding pancaking, meaning an
      integrated approach to finding solutions is needed. 

PMID- 26198186
TI  - The effects of tautomerization and protonation on the adenine-cytosine
      mismatches: a density functional theory study.
AB  - In the present work, we demonstrate the results of a theoretical study concerned
      with the question how tautomerization and protonation of adenine affect the
      various properties of adenine-cytosine mismatches. The calculations, in gas phase
      and in water, are performed at B3LYP/6-311++G(d,p) level. In gas phase, it is
      observed that any tautomeric form of investigated mismatches is more stabilized
      when adenine is protonated. As for the neutral mismatches, the mismatches
      containing amino form of cytosine and imino form of protonated adenine are more
      stable. The role of aromaticity on the stability of tautomeric forms of
      mismatches is investigated by NICS(1)ZZ index. The stability of mispairs
      decreases by going from gas phase to water. It can be explained using dipole
      moment parameter. The influence of hydrogen bonds on the stability of mismatches
      is examined by atoms in molecules and natural bond orbital analyses. In addition
      to geometrical parameters and binding energies, the study of the topological
      properties of electron charge density aids in better understanding of these
      mispairs. 

PMID- 26198185
TI  - Cognitive-Behavioral Therapy: How Medical Providers Can Increase Patient and
      Family Openness and Access to Evidence-Based Multimodal Therapy for Pediatric
      Migraine.
AB  - Although evidence supports the recommendation for cognitive-behavioral therapy
      (CBT) for pediatric migraine, few children actually receive this evidence-based
      intervention. In this article, we briefly review the most recent empirical
      evidence supporting CBT. We then identify both provider- and system-related
      barriers as well as patient-related barriers. Finally, we provide practical
      solutions to addressing these barriers in the service of facilitating children
      receiving optimal comprehensive management of their headaches. 

PMID- 26198187
TI  - Identification of Manganese Superoxide Dismutase from Sphingobacterium sp. T2 as
      a Novel Bacterial Enzyme for Lignin Oxidation.
AB  - The valorization of aromatic heteropolymer lignin is an important unsolved
      problem in the development of a biomass-based biorefinery, for which novel high
      activity biocatalysts are needed. Sequencing of the genomic DNA of lignin
      degrading bacterial strain Sphingobacterium sp. T2 revealed no matches to known
      lignin-degrading genes. Proteomic matches for two manganese superoxide dismutase
      proteins were found in partially purified extracellular fractions. Recombinant
      MnSOD1 and MnSOD2 were both found to show high activity for oxidation of
      Organosolv and Kraft lignin, and lignin model compounds, generating multiple
      oxidation products. Structure determination revealed that the products result
      from aryl-Calpha and Calpha-Cbeta bond oxidative cleavage and O-demethylation.
      The crystal structure of MnSOD1 was determined to 1.35 A resolution, revealing a
      typical MnSOD homodimer harboring a five-coordinate trigonal bipyramidal Mn(II)
      center ligated by three His, one Asp, and a water/hydroxide in each active site.
      We propose that the lignin oxidation reactivity of these enzymes is due to the
      production of a hydroxyl radical, a highly reactive oxidant. This is the first
      demonstration that MnSOD is a microbial lignin-oxidizing enzyme. 

PMID- 26198188
TI  - Why did children grow so well at hard times? The ultimate importance of pathogen
      control during puberty.
AB  - BACKGROUND AND OBJECTIVES: Secular increase in human height and performance
      occurred in Europe throughout the 20th century despite the temporally worsening
      access to nutrients during and after World War II. This pattern is paradoxical
      under the assumption of the major impact of pre- and postnatal growth conditions
      for determination of adult size and human capital. METHODOLOGY: We examined the
      anthropometric parameters of Estonian girls born between 1938 and 1953, and
      measured around the age of 17 (n = 1475). This period involved two opposite
      trends in the economic and epidemiological situation: increasing birth-time
      economic hardships during the war and particularly in the post-war period, and
      decreasing infant mortality (a proxy of disease burden) after 1947. RESULTS:
      Height of girls was negatively affected by the number of siblings and positively
      by parental socioeconomic position, but these effects were weaker than the
      secular trend. Leg length (an indicator of pre-pubertal growth conditions) was
      independent of age and birth date while all other traits, including measures of
      performance (cranial volume, lung capacity and handgrip strength) showed
      acceleration. The best predictor of size at age 17 was, in most cases, infant
      mortality in the year when the girls were aged 11. CONCLUSIONS AND IMPLICATIONS:
      Reduction of disease burden during pubertal growth can override effects of
      resource shortage at birth. Our results also support the idea that increasing
      efficiency of pathogen control can contribute to the secular increase in
      cognitive abilities, i.e. the Flynn effect, and that epidemiological transition
      is the main driver of secular increase in human capital.

PMID- 26198189
TI  - The evolution of capture myopathy in hooved mammals: a model for human stress
      cardiomyopathy?
AB  - BACKGROUND AND OBJECTIVES: Capture myopathy (CM) syndromes in wildlife may be a
      model for human stress cardiomyopathy, including Takotsubo cardiomyopathy.
      Emotional stress or grief may trigger heart attack-like symptoms, and
      occasionally, sudden death in some humans. Similarly, wildlife exposed to
      predatory stresses, chase, or capture occasionally results in sudden death. To
      better understand the nature of vulnerability to stress-induced sudden death, we
      studied cases of CM in hooved mammals-ungulates-and hypothesized that CM would be
      associated with a syndrome of longevity-related traits. METHODOLOGY: We
      reconstructed the evolution of CM in ungulates then determined how a set of life
      history traits explained variation in the likelihood that CM was reported.
      RESULTS: CM is broadly reported, but not in all genera, and phylogenetic analyses
      suggest that it is an evolutionarily labile trait. We found that the following
      traits were significantly associated with reports of CM: greater brain mass,
      faster maximum running speed, greater minimum group size and greater maximum
      longevity. CONCLUSIONS AND IMPLICATIONS: CM may be an unavoidable consequence of
      adaptations to reduce predation risk that include increased running speed,
      sociality and having larger brains. Moreover, longer-lived species seem to be
      more likely to be susceptible to CM. Exploring variable susceptibility to CM
      highlights the evolutionary origins of the disorder, potential basic mechanisms
      that underlie vulnerability to the phenomenon, and the potential for reduction of
      risk through modification of life history trajectory.

PMID- 26198191
TI  - Diagnostic delay in hidradenitis suppurativa is a global problem.

PMID- 26198190
TI  - Microbiology and ecology are vitally important to premedical curricula.
AB  - Despite the impact of the human microbiome on health, an appreciation of
      microbial ecology is yet to be translated into mainstream medical training and
      practice. The human microbiota plays a role in the development of the immune
      system, in the development and function of the brain, in digestion, and in host
      defense, and we anticipate that many more functions are yet to be discovered. We
      argue here that without formal exposure to microbiology and ecology-fields that
      explore the networks, interactions and dynamics between members of populations of
      microbes-vitally important links between the human microbiome and health will be
      overlooked. This educational shortfall has significant downstream effects on
      patient care and biomedical research, and we provide examples from current
      research highlighting the influence of the microbiome on human health. We
      conclude that formally incorporating microbiology and ecology into the premedical
      curricula is invaluable to the training of future health professionals and
      critical to the development of novel therapeutics and treatment practices. 

PMID- 26198192
TI  - Combination therapy of varenicline with nicotine replacement therapy is better
      than varenicline alone: a systematic review and meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Smoking is a major preventable cause of morbidity and premature death
      worldwide. Both varenicline and nicotine replacement therapy (NRT) help achieve
      smoking cessation. However, limited evidence exists regarding whether combination
      of varenicline and NRT is more effective than either alone. The aim of this
      research was to investigate the efficacy and safety of varenicline combined with
      NRT. METHODS: A systematic search of MEDLINE, EMBASE, ClinicalTrial.gov, and
      Cochrane Library was conducted in November 2014. Two authors independently
      reviewed and selected randomized controlled trials. The quality of the studies
      was evaluated by the Jadad score. We carried out meta-analysis of both early
      (abstinence rate assessed before or at the end of treatment) and late (assessed
      after the end of the treatment) outcomes. RESULTS: Three randomized controlled
      trials with 904 participants were included in this meta-analysis. All three were
      comparing combination therapy with varenicline therapy alone. The late outcomes
      were assessed in 2 of the 3 trials. Both the early and late outcomes were
      favorable for combination therapy (OR = 1.50, 95 % CI 1.14 to 1.97; OR = 1.62, 95
      % CI 1.18 to 2.23, respectively). However, this significance diminished after
      eliminating a study with pre-cessation treatment using nicotine patch. The most
      common adverse events were nausea, insomnia, abnormal dreams, and headache. One
      study reported more skin reactions (14.4 % vs 7.8 %; p = 0.03) associated with
      combination therapy. CONCLUSIONS: Combination therapy is more effective than
      varenicline alone, especially if pre-cessation treatment of nicotine patch is
      administrated. Adverse events of combination therapy are similar to mono-therapy
      except for skin reactions.

PMID- 26198193
TI  - Neuroprotective Effects of (-)-Epigallocatechin-3-Gallate Against Focal Cerebral
      Ischemia/Reperfusion Injury in Rats Through Attenuation of Inflammation.
AB  - Stroke is the second leading cause of death among adults worldwide. (-)
      Epigallocatechin-3-gallate (EGCG) has been demonstrated to exhibit
      neuroprotective functions in cerebral ischemia/reperfusion injury. However, the
      underlying mechanisms in this process and its contribution to the protection
      function remain unknown. The current study examined the neuroprotective effects
      of EGCG after transient middle cerebral artery occlusion (tMCAO) in rats. tMCAO
      for 120 min was induced in male Sprague-Dawley rats treated with EGCG (50 mg/kg,
      i.p.) or Vehicle immediately after reperfusion. Neurological score, infarct ratio
      and inflammation-related molecules (assessed by 2,3,5-triphenyltetrazolium
      chloride, enzyme-linked immunosorbent assays, quantitative real-time PCR or
      western blotting) were estimated at 24 h after operation. EGCG prevented the
      impairment of neurological function and decreased the infarct volume, compared
      with the Vehicle group. The inflammation-related molecules TNF-alpha, IL-1beta,
      IL-6 levels usually caused by ischemia/reperfusion were significantly ameliorated
      by EGCG. EGCG also inhibited the upregulation of nuclear factor-kappa B/p65 (NF
      kappaB/p65), and induction of cyclooxygenase 2 and inducible nitric oxide
      synthase. The present study indicates that EGCG may be a promising therapeutic
      agent for cerebral ischemia/reperfusion injury through attenuation of
      inflammation.

PMID- 26198195
TI  - The AJT Report.

PMID- 26198194
TI  - Phosphatidylinositol 3-Kinase Couples Localised Calcium Influx to Activation of
      Akt in Central Nerve Terminals.
AB  - The efficient retrieval of synaptic vesicle membrane and cargo in central nerve
      terminals is dependent on the efficient recruitment of a series of endocytosis
      modes by different patterns of neuronal activity. During intense neuronal
      activity the dominant endocytosis mode is activity-dependent endocytosis (ADBE).
      Triggering of ADBE is linked to calcineurin-mediated dynamin I dephosphorylation
      since the same stimulation intensities trigger both. Dynamin I dephosphorylation
      is maximised by a simultaneous inhibition of its kinase glycogen synthase kinase
      3 (GSK3) by the protein kinase Akt, however it is unknown how increased neuronal
      activity is transduced into Akt activation. To address this question we
      determined how the activity-dependent increases in intracellular free calcium
      ([Ca(2+)]i) control activation of Akt. This was achieved using either trains of
      high frequency action potentials to evoke localised [Ca(2+)]i increases at active
      zones, or a calcium ionophore to raise [Ca(2+)]i uniformly across the nerve
      terminal. Through the use of either non-specific calcium channel antagonists or
      intracellular calcium chelators we found that Akt phosphorylation (and subsequent
      GSK3 phosphorylation) was dependent on localised [Ca(2+)]i increases at the
      active zone. In an attempt to determine mechanism, we antagonised either
      phosphatidylinositol 3-kinase (PI3K) or calmodulin. Activity-dependent
      phosphorylation of both Akt and GSK3 was arrested on inhibition of PI3K, but not
      calmodulin. Thus localised calcium influx in central nerve terminals activates
      PI3K via an unknown calcium sensor to trigger the activity-dependent
      phosphorylation of Akt and GSK3. 

PMID- 26198198
TI  - A Surprising Renal Graft Doppler Ultrasound in a Kidney-Heart Transplant
      Recipient: When Hemodynamic Analysis Is Even More Informative Than Usual.

PMID- 26198199
TI  - Erratum.

PMID- 26198201
TI  - A novel human leukocyte antigen (HLA) allele, HLA-DRB1*08:71, was found in a
      Taiwanese unrelated hematopoietic stem cell donor.
AB  - One nucleotide substitution at residue 367 of HLA-DRB1*08:03:02 results in a new
      allele, HLA-DRB1*08:71. 

PMID- 26198202
TI  - Adsorption of rationally designed "surf-tides" to a liquid-crystal interface.
AB  - The interfacial adsorption of proteins in surfactant laden systems occurs both in
      nature and industrial processing, yet much of the fundamental behavior behind
      these systems is still not well understood. We report the development of a system
      that monitors optical transitions of a liquid-crystalline/aqueous interface to
      examine the dynamics of adsorption of two rationally designed model peptide
      molecules. The two molecules synthesized in this study were both designed to
      become surface-active upon folding and contain the same net charge of +3, but one
      of the peptides, K-2.5, has its three charges separated by 2.5 amino acids as
      compared to K-6.0, which has its three charges separated by 6 amino acids. Our
      study examines the roles that surfactant adsorption, peptide charge distribution
      and secondary structure have on the relative adsorption dynamics of these two
      models peptides onto a fluid/fluid interface. Using the optical detection of
      molecular adsorption and image analysis of these events, we obtain quantitative
      information about the dynamics as a function of the charge spacing and initial
      peptide concentration. We show that both peptides initially follow a diffusion
      limited adsorption model onto the interface. Additionally, our results suggest
      that the K-6.0 peptides demonstrate enhanced adsorption kinetics, where the
      enhanced rates are a consequence of the well-folded adsorbed state and spatial
      distribution on the surface. These findings provide further insights into the
      role that charge spacing has on secondary structure and subsequently the dynamics
      of adsorption, while developing a versatile system capable of extracting
      quantitative information from a simple inexpensive optical system. 

PMID- 26198203
TI  - Ultraviolet-light-driven doping modulation in chemical vapor deposition grown
      graphene.
AB  - The tuning of charge carrier density of graphene is an essential factor to
      achieve the integration of high-efficiency electronic and optoelectronic devices.
      We demonstrate the reversible doping in graphene using deep ultraviolet (UV)
      irradiation and treatment with O2 and N2 gases. The Dirac point shift towards a
      positive gate voltage of chemical vapor deposition grown graphene field-effect
      transistors confirms the p-type doping, which is observed under UV irradiation
      and treatment with O2 gas, while it restores its pristine state after treatment
      with N2 gas under UV irradiation. The emergence of an additional peak in the X
      ray photoelectron spectra during UV irradiation and treatment with O2 gas
      represents the oxidation of graphene, and the elimination of this peak during UV
      irradiation and treatment with N2 gas reveals the restoration of graphene in its
      pristine state. The shift in the G and 2D bands in Raman spectra towards higher
      and then lower wavenumber also suggests p-type doping and then reversible doping
      in graphene. The controlled doping and its reversibility in large area grown
      graphene offer a new vision for electronic applications. 

PMID- 26198204
TI  - Ecdysone promotes growth of imaginal discs through the regulation of Thor in D.
      melanogaster.
AB  - Animals have a determined species-specific body size that results from the
      combined action of hormones and signaling pathways regulating growth rate and
      duration. In Drosophila, the steroid hormone ecdysone controls developmental
      transitions, thereby regulating the duration of the growth period. Here we show
      that ecdysone promotes the growth of imaginal discs in mid-third instar larvae,
      since imaginal discs from larvae with reduced or no ecdysone synthesis are
      smaller than wild type due to smaller and fewer cells. We show that insulin-like
      peptides are produced and secreted normally in larvae with reduced ecdysone
      synthesis, and upstream components of insulin/insulin-like signaling are
      activated in their discs. Instead, ecdysone appears to regulate the growth of
      imaginal discs via Thor/4E-BP, a negative growth regulator downstream of the
      insulin/insulin-like growth factor/Tor pathways. Discs from larvae with reduced
      ecdysone synthesis have elevated levels of Thor, while mutations in Thor
      partially rescue their growth. The regulation of organ growth by ecdysone is
      evolutionarily conserved in hemimetabolous insects, as shown by our results
      obtained using Blattella germanica. In summary, our data provide new insights
      into the relationship between components of the insulin/insulin-like/Tor and
      ecdysone pathways in the control of organ growth. 

PMID- 26198205
TI  - Computed tomographic colonography compared with colonoscopy or barium enema for
      diagnosis of colorectal cancer in older symptomatic patients: two multicentre
      randomised trials with economic evaluation (the SIGGAR trials).
AB  - BACKGROUND: Computed tomographic colonography (CTC) is a relatively new
      diagnostic test that may be superior to existing alternatives to investigate the
      large bowel. OBJECTIVES: To compare the diagnostic efficacy, acceptability,
      safety and cost-effectiveness of CTC with barium enema (BE) or colonoscopy.
      DESIGN: Parallel randomised trials: BE compared with CTC and colonoscopy compared
      with CTC (randomisation 2 : 1, respectively). SETTING: A total of 21 NHS
      hospitals. PARTICIPANTS: Patients aged >= 55 years with symptoms suggestive of
      colorectal cancer (CRC). INTERVENTIONS: CTC, BE and colonoscopy. MAIN OUTCOME
      MEASURES: For the trial of CTC compared with BE, the primary outcome was the
      detection rate of CRC and large polyps (>= 10 mm), with the proportion of
      patients referred for additional colonic investigation as a secondary outcome.
      For the trial of CTC compared with colonoscopy, the primary outcome was the
      proportion of patients referred for additional colonic investigation, with the
      detection rate of CRC and large polyps as a secondary outcome. Secondary outcomes
      for both trials were miss rates for cancer (via registry data), all-cause
      mortality, serious adverse events, patient acceptability, extracolonic pathology
      and cost-effectiveness. RESULTS: A total of 8484 patients were registered and
      5384 were randomised and analysed (BE trial: 2527 BE, 1277 CTC; colonoscopy
      trial: 1047 colonoscopy, 533 CTC). Detection rates in the BE trial were 7.3%
      (93/1277) for CTC, compared with 5.6% (141/2527) for BE (p = 0.0390). The
      difference was due to better detection of large polyps by CTC (3.6% vs. 2.2%; p =
      0.0098), with no significant difference for cancer (3.7% vs. 3.4%; p = 0.66).
      Significantly more patients having CTC underwent additional investigation (23.5%
      vs. 18.3%; p = 0.0003). At the 3-year follow-up, the miss rate for CRC was 6.7%
      for CTC (three missed cancers) and 14.1% for BE (12 missed cancers).
      Significantly more patients randomised to CTC than to colonoscopy underwent
      additional investigation (30% vs. 8.2%; p < 0.0001). There was no significant
      difference in detection rates for cancer or large polyps (10.7% for CTC vs. 11.4%
      for colonoscopy; p = 0.69), with no difference when cancers (p = 0.94) and large
      polyps (p = 0.53) were analysed separately. At the 3-year follow-up, the miss
      rate for cancer was nil for colonoscopy and 3.4% for CTC (one missed cancer).
      Adverse events were uncommon for all procedures. In 1042 of 1748 (59.6%) CTC
      examinations, at least one extracolonic finding was reported, and this proportion
      increased with age (p < 0.0001). A total of 149 patients (8.5%) were subsequently
      investigated, and extracolonic neoplasia was diagnosed in 79 patients (4.5%) and
      malignancy in 29 (1.7%). In the short term, CTC was significantly more acceptable
      to patients than BE or colonoscopy. Total costs for CTC and colonoscopy were
      finely balanced, but CTC was associated with higher health-care costs than BE.
      The cost per large polyp or cancer detected was L4235 (95% confidence interval
      L395 to L9656). CONCLUSIONS: CTC is superior to BE for detection of cancers and
      large polyps in symptomatic patients. CTC and colonoscopy detect a similar
      proportion of large polyps and cancers and their costs are also similar. CTC
      precipitates significantly more additional investigations than either BE or
      colonoscopy, and evidence-based referral criteria are needed. Further work is
      recommended to clarify the extent to which patients initially referred for
      colonoscopy or BE undergo subsequent abdominopelvic imaging, for example by
      computed tomography, which will have a significant impact on health economic
      estimates. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95152621.

PMID- 26198206
TI  - Prediction of Links and Weights in Networks by Reliable Routes.
AB  - Link prediction aims to uncover missing links or predict the emergence of future
      relationships from the current network structure. Plenty of algorithms have been
      developed for link prediction in unweighted networks, but only a few have been
      extended to weighted networks. In this paper, we present what we call a "reliable
      route method" to extend unweighted local similarity indices to weighted ones.
      Using these indices, we can predict both the existence of links and their
      weights. Experiments on various real-world networks suggest that our reliable
      route weighted resource-allocation index performs noticeably better than others
      with respect to weight prediction. For existence prediction it is either the
      highest or very close to the highest. Further analysis shows a strong positive
      correlation between the clustering coefficient and prediction accuracy. Finally,
      we apply our method to the prediction of missing protein-protein interactions and
      their confidence scores from known PPI networks. Once again, our reliable-route
      method shows the highest accuracy. 

PMID- 26198207
TI  - Predicting the stability of large structured food webs.
AB  - The stability of ecological systems has been a long-standing focus of ecology.
      Recently, tools from random matrix theory have identified the main drivers of
      stability in ecological communities whose network structure is random. However,
      empirical food webs differ greatly from random graphs. For example, their degree
      distribution is broader, they contain few trophic cycles, and they are almost
      interval. Here we derive an approximation for the stability of food webs whose
      structure is generated by the cascade model, in which 'larger' species consume
      'smaller' ones. We predict the stability of these food webs with great accuracy,
      and our approximation also works well for food webs whose structure is determined
      empirically or by the niche model. We find that intervality and broad degree
      distributions tend to stabilize food webs, and that average interaction strength
      has little influence on stability, compared with the effect of variance and
      correlation. 

PMID- 26198209
TI  - Tunability Limit of Photoluminescence in Colloidal Silicon Nanocrystals.
AB  - Luminescent silicon nanocrystals (Si NCs) have attracted tremendous research
      interest. Their size dependent photoluminescence (PL) shows great promise in
      various optoelectronic and biomedical applications and devices. However, it
      remains unclear why the exciton emission is limited to energy below 2.1 eV, no
      matter how small the nanocrystal is. Here we interpret a nanosecond transient
      yellow emission band at 590 nm (2.1 eV) as a critical limit of the wavelength
      tunability in colloidal silicon nanocrystals. In the "large size" regime (d > ~3
      nm), quantum confinement dominantly determines the PL wavelength and thus the PL
      peak blue shifts upon decreasing the Si NC size. In the "small size" regime (d <
      ~2 nm) the effect of the yellow band overwhelms the effect of quantum confinement
      with distinctly increased nonradiative trapping. As a consequence, the
      photoluminescence peak does not exhibit any additional blue shift and the quantum
      yield drops abruptly with further decreasing the size of the Si NCs. This finding
      confirms that the PL originating from the quantum confined core states can only
      exist in the red/near infrared with energy below 2.1 eV; while the blue/green PL
      originates from surface related states and exhibits nanosecond transition. 

PMID- 26198208
TI  - Idiopathic (primary) achalasia: a review.
AB  - Idiopathic achalasia is a primary esophageal motor disorder characterized by loss
      of esophageal peristalsis and insufficient lower esophageal sphincter relaxation
      in response to deglutition. Patients with achalasia commonly complain of
      dysphagia to solids and liquids, bland regurgitation often unresponsive to an
      adequate trial of proton pump inhibitor, and chest pain. Weight loss is present
      in many, but not all patients. Although the precise etiology is unknown, it is
      often thought to be either autoimmune, viral immune, or neurodegenerative. The
      diagnosis is based on history of the disease, barium esophagogram, and esophageal
      motility testing. Endoscopic assessment of the gastroesophageal junction and
      gastric cardia is necessary to rule out malignancy. Newer diagnostic modalities
      such as high resolution manometry help in predicting treatment response in
      achalasia based on esophageal pressure topography patterns identifying three
      phenotypes of achalasia (I-III) and outcome studies suggest better treatment
      response with types I and II compared to type III. Although achalasia cannot be
      permanently cured, excellent outcomes are achieved in over 90 % of patients.
      Current medical and surgical therapeutic options (pneumatic dilation, endoscopic
      and surgical myotomy, and pharmacologic agents) aim at reducing the LES pressure
      and facilitating esophageal emptying by gravity and hydrostatic pressure of
      retained food and liquids. Either graded pneumatic dilatation or laparoscopic
      surgical myotomy with a partial fundoplication are recommended as initial therapy
      guided by patient age, gender, preference, and local institutional expertise. The
      prognosis in achalasia patients is excellent. Most patients who are appropriately
      treated have a normal life expectancy but the disease does recur and the patient
      may need intermittent treatment.

PMID- 26198210
TI  - Prevalence of antileptospiral serum antibodies in dogs in Ireland.
AB  - A total of 474 serum samples from client owned Irish dogs were tested for the
      presence of antibodies to serovars Canicola, Icterohaemorrhagiae, Bratislava,
      Autumnalis, Pomona, Altodouro, Grippotyphosa, Mozdok, Hardjobovis and Ballum. Six
      per cent of dogs presented to veterinary practitioners for problems unrelated to
      leptospirosis showed evidence of prior exposure to leptospiral serovars belonging
      to the serogropus Ballum, Australis, Pomona and Sejroe. One unvaccinated dog
      suspected to have leptospirosis showed seroconversion to serogroup
      Icterohaemorrhagiae. Based on these results the authors conclude that canine
      exposure to serogroup Ballum should be monitored because dogs may serve as
      sentinels for this serovar in the environment. Vaccination with multivalent
      vaccines containing serovar Bratislava in addition to serogroups
      Icterohaemorrhagiae and Canicola is advisable. 

PMID- 26198211
TI  - Clinical reasoning in canine spinal disease: what combination of clinical
      information is useful?
AB  - Spinal disease in dogs is commonly encountered in veterinary practice. Numerous
      diseases may cause similar clinical signs and presenting histories. The study
      objective was to use statistical models to identify combinations of discrete
      parameters from the patient signalment, history and neurological examination that
      could suggest the most likely diagnoses with statistical significance. A
      retrospective study of 500 dogs referred to the Queen Mother Hospital for Animals
      before June 2012 for the investigation of spinal disease was performed. Details
      regarding signalment, history, physical and neurological examinations,
      neuroanatomical localisation and imaging data were obtained. Univariate analyses
      of variables (breed, age, weight, onset, deterioration, pain, asymmetry,
      neuroanatomical localisation) were performed, and variables were retained in a
      multivariate logistic regression model if P<0.05. Leading diagnoses were
      intervertebral disc extrusion (IVDE, n=149), intervertebral disc protrusion
      (n=149), ischaemic myelopathy (IM, n=48) and neoplasms (n=44). Multivariate
      logistic regression characterised IM and acute non-compressive nucleus pulposus
      extrusions as the only peracute onset, non-progressive, non-painful and
      asymmetrical T3-L3 myelopathies. IVDE was most commonly characterised as acute
      onset, often deteriorating, painful and largely symmetrical T3-L3 myelopathy.
      This study suggests that most spinal diseases cause distinctive combinations of
      presenting clinical parameters (signalment, onset, deterioration, pain,
      asymmetry, neuroanatomical localisation). Taking particular account of these
      parameters may aid decision making in a clinical setting. 

PMID- 26198212
TI  - First report of natural BoHV-1 infection in water buffalo.

PMID- 26198213
TI  - Diseases in pet guinea pigs: a retrospective study in 1000 animals.
AB  - Guinea pigs are commonly kept as pet animals; however, information about
      particular disease prevalence is lacking. The objective of this article was to
      present disease prevalence in 1000 pet guinea pigs from private owners divided
      into three age groups: under two years; between two and five years; and above
      five years. Medical records of guinea pigs (Cavia aperea f. porcellus) that were
      presented to the authors' clinic in the period from January 2008 to August 2013
      were reviewed. The most commonly diagnosed disease in guinea pigs was dental
      disease (36.3 per cent), with higher prevalence in the middle age group (P<0.001)
      and in males (P<0.001) rather than females. Skin problems were seen as the second
      most common disease (33.3 per cent), with higher prevalence in male guinea pigs
      (P<0.001) and in animals younger than two years (P<0.001). Ovarian cystic disease
      was the third most commonly seen disorder, with higher prevalence in females
      older than two years (P<0.001). Other common health disorders included
      gastrointestinal stasis, heterotopic ciliary body calcifications, fatty eye and
      tibiofemoral osteoarthritis. Only 81 guinea pigs from a total of 1000 animals
      were healthy. This is the first study to describe the disease prevalence in three
      age groups of pet guinea pigs.

PMID- 26198215
TI  - Disseminated extranodal marginal zone lymphoma involving the gastrocnemius muscle
      with sural neurolymphomatosis.

PMID- 26198214
TI  - Distribution Analyzer, a methodology for identifying and clustering outlier
      conditions from single-cell distributions, and its application to a Nanog
      reporter RNAi screen.
AB  - BACKGROUND: Chemical or small interfering (si) RNA screens measure the effects of
      many independent experimental conditions, each applied to a population of cells
      (e.g., all of the cells in a well). High-content screens permit a readout (e.g.,
      fluorescence, luminescence, cell morphology) from each cell in the population.
      Most analysis approaches compare the average effect on each population,
      precluding identification of outliers that affect the distribution of the
      reporter in the population but not its average. Other approaches only measure
      changes to the distribution with a single parameter, precluding accurate
      distinction and clustering of interesting outlier distributions. RESULTS: We
      describe a methodology to identify outlier conditions by considering the cell
      level measurements from each condition as a sample of an underlying distribution.
      With appropriate selection of a distance metric, all effects can be embedded in a
      fixed-dimensionality Euclidean basis, facilitating identification and clustering
      of biologically interesting outliers. We demonstrate that measurement of
      distances with the Hellinger distance metric offers substantial computational
      efficiencies over alternative metrics. We validate this methodology using an RNA
      interference (RNAi) screen in mouse embryonic stem cells (ESC) with a Nanog
      reporter. The methodology clusters effects of multiple control siRNAs into their
      true identities better than conventional approaches describing the median cell
      fluorescence or the commonly used Kolmogorov-Smirnov distance between the
      observed fluorescence distribution and the null distribution. It identifies
      outlier genes with effects on the reporter distribution that would have been
      missed by other methods. Among them, siRNA targeting Chek1 leads to a wider Nanog
      reporter fluorescence distribution. Similarly, siRNA targeting Med14 or Med27
      leads to a narrower Nanog reporter fluorescence distribution. We confirm the
      roles of these three genes in regulating pluripotency by mRNA expression and
      alkaline phosphatase staining using independent short hairpin (sh) RNAs.
      CONCLUSIONS: Using our methodology, we describe each experimental condition by a
      probability distribution. Measuring distances between probability distributions
      permits a multivariate rather than univariate readout. Clustering points derived
      from these distances allows us to obtain greater biological insight than methods
      based solely on single parameters. We find several outliers from a mouse ESC RNAi
      screen that we confirm to be pluripotency regulators. Many of these outliers
      would have been missed by other analysis methods.

PMID- 26198216
TI  - Incidence of recurrent seizures following hospital discharge in patients with
      LPDs (PLEDs) and nonconvulsive seizures recorded on continuous EEG in the
      critical care setting.
AB  - PURPOSE: Continuous EEG (cEEG) has helped to identify nonconvulsive seizures
      (NCS) and nonconvulsive status epilepticus (NCSE) along with lateralized periodic
      patterns (LPDs or PLEDs) in ICU patients with much higher frequency than
      previously appreciated, but understanding their implications may be more complex.
      The aim of this study was to investigate the incidence of recurrent seizures
      after hospital discharge and their associated factors in patients with PLEDs and
      NCS in the critical care setting. METHODS: After IRB approval, we used our EEG
      reporting database to find 200 consecutive patients who had PLEDs and/or NCSs on
      cEEG. Patients with less than 3 months of follow-up were excluded. Remaining
      patients were divided into three groups: PLEDs+Seizure (NCS/NCSE), PLEDs only,
      and Seizures (NCS/NCSE) only. Medical records were reviewed to gather
      demographical and clinical details. Univariate data analysis was done using JMP
      9.0 (Marlow, Buckinghamshire, UK). RESULTS: There were 51 patients in
      'PLEDs+Seizure' group, 45 in 'PLEDs only' group, and 22 in 'Seizure only' group.
      Ischemic stroke, hemorrhage, and tumors were the top three etiologies. Nearly 47%
      of our study population had postdischarge seizures during a mean follow-up period
      of 11.9 (+/-6) months. We found that 24.4% of patients in the PLEDs only group
      had seizures after discharge, which increased to 60.7% if they had seizures as
      well during their ICU stay. Slightly more than 52% of patients had a
      postdischarge EEG, of which, 59% was in the form of inpatient cEEG during a
      rehospitalization, accounting for 30.5% of the total study population. It was an
      indicator of high readmission rates in this population. CONCLUSION: Almost every
      other patient with PLEDs and/or NCS on cEEG had seizures after ICU discharge. A
      quarter of patients on cEEG in the ICU with PLEDs alone had seizures after
      discharge, and after excluding prior epilepsy, 17% of patients with PLEDs had
      seizures on follow-up. This was dramatically increased with the recording of
      PLEDs with NCS, with 60% of patients having seizures after discharge from the ICU
      and 48% of patients after excluding prior epilepsy. Patients with NCS on cEEG
      alone had 63% chance of seizure recurrence that dropped to 38% with exclusion of
      prior epilepsy. Future studies are needed to define the postdischarge outcomes
      including seizure recurrence in this patient population. This article is part of
      a Special Issue entitled "Status Epilepticus".

PMID- 26198217
TI  - Deep hypothermia for the treatment of refractory status epilepticus.
AB  - In a rat model of status epilepticus (SE) induced by lithium and pilocarpine and
      refractory to midazolam, deep hypothermia (20  degrees C for 30 min) reduced EEG
      power over 50-fold, stopped SE within 12 min, and reduced EEG spikes by 87%.
      Hypothermia deserves further investigation as a treatment of last resort for
      refractory SE. This article is part of a Special Issue entitled "Status
      Epilepticus".

PMID- 26198219
TI  - Calophyllolide content in Calophyllum inophyllum at different stages of maturity
      and its osteogenic activity.
AB  - Calophyllum inophyllum is a coastal plant rich in natural substances. Its
      ingredients have been used for the development of an anti-human immunodeficiency
      virus (HIV) drug. In this study, we collected C. inophyllum fruit, and the
      ethanol extract of the fruit was chromatographically separated using silica gel
      and Sephadex LH-20 columns to obtain the major compound, calophyllolide. The
      fruits were harvested from September to December in 2011; a quantitative analysis
      of the calophyllolide content was conducted using HPLC to explore the differences
      between the different parts of the fruit during the growing season. The results
      showed that in fruits of C. inophyllum, calophyllolide exists only in the nuts,
      and dried nuts contain approximately 2 mg.g-1 of calophyllolide. The
      calophyllolide levels in the nuts decreased during maturity. In addition,
      calophyllolide dose-dependently enhanced alkaline phosphatase (ALP) activity in
      murine osteoblastic MC3T3-E1 cells, without significant cytotoxicity. The
      expression of osteoblastic genes, ALP and osteocalcin (OCN), were increased by
      calophyllolide. Calophyllolide induced osteoblasts differentiation also evidenced
      by increasing mineralization and ALP staining. 

PMID- 26198218
TI  - 'I think positivity breeds positivity': a qualitative exploration of the role of
      family members in supporting those with chronic musculoskeletal pain to stay at
      work.
AB  - BACKGROUND: It is proposed that family members are important sources of support
      in helping those with chronic musculoskeletal pain to remain at work, but the
      phenomenon remains largely unexplored. The aim of this study was to examine the
      extent and nature of support provided by family members in this respect. METHODS:
      Qualitative data were collected from workers and their 'significant others'
      (spouses/partners/close family members) in two un-related studies focused on
      working with pain; one conducted in the United Kingdom (n = 10 dyads) and one in
      the Netherlands (n = 21 dyads). Thematic analysis techniques were applied to both
      sets of data independently, and findings were then assimilated to establish
      common themes. RESULTS: Findings were broadly similar in both studies. Workers
      acknowledged significant other support in helping them to manage their pain and
      remain at work, and their descriptions of the type of support provided and
      required were echoed by their significant others. Three common themes were
      identified - 'connectivity', 'activity' and 'positivity'. Worker and significant
      other responses were largely congruent, but significant others provided more in
      depth information on the nature of their support, their concerns and the impact
      on their relationship. CONCLUSIONS: This research presents novel insights about
      the specific contribution made by significant others in helping their relatives
      with chronic musculoskeletal pain to stay at work. These findings add to the
      under-represented 'social' dimension of the biopsychosocial model currently
      applied to our understanding and treatment of pain, and point to harnessing
      support from significant others as a potentially effective management strategy.

PMID- 26198220
TI  - Study on the spectrophotometric detection of free fatty acids in palm oil
      utilizing enzymatic reactions.
AB  - In this paper, a comprehensive study has been made on the detection of free fatty
      acids (FFAs) in palm oil via an optical technique based on enzymatic aminolysis
      reactions. FFAs in crude palm oil (CPO) were converted into fatty hydroxamic
      acids (FHAs) in a biphasic lipid/aqueous medium in the presence of immobilized
      lipase. The colored compound formed after complexation between FHA and vanadium
      (V) ion solution was proportional to the FFA content in the CPO samples and was
      analyzed using a spectrophotometric method. In order to develop a rapid detection
      system, the parameters involved in the aminolysis process were studied. The
      utilization of immobilized lipase as catalyst during the aminolysis process
      offers simplicity in the product isolation and the possibility of conducting the
      process under extreme reaction conditions. A good agreement was found between the
      developed method using immobilized Thermomyces lanuginose lipase as catalyst for
      the aminolysis process and the Malaysian Palm Oil Board (MPOB) standard titration
      method (R2 = 0.9453). 

PMID- 26198221
TI  - Multidimensional transition metal complexes based on 3-amino-1H-1,2,4-triazole-5
      carboxylic acid: from discrete mononuclear complexes to layered materials.
AB  - The synthesis and structural characterization of five transition metal complexes
      with different dimensionality and incorporating residues of 3-amino-1H-1,2,4
      triazole-5-carboxylic acid (H2atrc) is reported: [Zn(Hatrc)2(H2O)] (1),
      [Mn(Hatrc)2(H2O)2].2H2O (2), [Fe2(Hatrc)4(OH)2].6H2O (3), [Cd(Hatrc)2(H2O)]n (4),
      and [Mn(atrc)(H2O)]n.nH2O (5). These materials could be prepared from solution (1
      3), diffusion (4), or hydrothermal reactions (5) with various anions and L:M
      ratios. Structural details were revealed by single crystal X-ray diffraction. The
      discrete units composing compounds 1-3, the polymeric 1D chain of 4 and the 2D
      layer of 5 are further extended into 3D supramolecular architectures through the
      formation of hydrogen bonds. 

PMID- 26198222
TI  - Mimicking the lipid peroxidation inhibitory activity of phospholipid
      hydroperoxide glutathione peroxidase (GPx4) by using fatty acid conjugates of a
      water-soluble selenolane.
AB  - A series of fatty acid conjugates of trans-3,4-dihydroxy-1-selenolane (DHS) were
      synthesized by reacting DHS with appropriate acid chlorides. The obtained
      monoesters were evaluated for their antioxidant capacities by the lipid
      peroxidation assay using a lecithin/cholesterol liposome as a model system. The
      observed antioxidant capacities against accumulation of the lipid hydroperoxide
      (LOOH) increased with increasing the alkyl chain length and became saturated for
      dodecanoic acid (C12) or higher fatty acid monoesters, for which the capacities
      were much greater than those of DHS, its tridecanoic acid (C13) diester, and
      PhSeSePh. On the other hand, the bacteriostatic activity of myristic acid (C14)
      monoester, evaluated through the colony formation assay using Bacillus subtilis,
      indicated that it has higher affinity to bacterial cell membranes than parent
      DHS. Since DHS-fatty acid conjugates would inhibit lipid peroxidation through
      glutathione peroxidase (GPx)-like 2e- mechanism, higher fatty acid monoesters of
      DHS can mimic the function of GPx4, which interacts with LOOH to reduce it to
      harmless alcohol (LOH). Importance of the balance between hydrophilicity and
      lipophilicity for the design of effective GPx4 mimics was suggested. 

PMID- 26198223
TI  - Molecular clusters size of Puerariae thomsonii radix aqueous decoction and
      relevance to oral absorption.
AB  - The multi-component system of traditional Chinese medicine (TCM) is very
      complicated. The clusters are dynamic aggregates whose molecules are held
      together by hydrogen-bonded, Van der Waals forces or the opposite charges of
      particles attract each other. In this paper, field emission scanning electron
      microscopy proved that molecules form clusters in Pueraria thomsonii Benth
      (Fenge) water decoction. Four kinds of Fenge water decoction, 0.07 g?mL-1 (F-1),
      0.1 g?mL-1 (F-2), 0.17 g?mL-1 (F-3), 0.35 g?mL-1 (F-4); F-1, average diameter of
      molecular was about 120 nm; F-2, 195 nm; F-3, 256 nm; and F-4, 480 nm. The
      molecular size was shown to depend on concentration. Rabbits were given equal
      does of 2.8 g?kg-1, to perfuse F-1, F-2, F-3, F-4 in volume of 80 mL, 56 mL, 33
      mL, 17 mL, respectively. At 0-180 min to collect 2 mL blood from the rabbit ears
      middle arteries for metabolism fingerprints, the results show the particle size
      of molecular is smaller, the absorption of drugs is better instead. The acute
      blood stasis model rats were treatment with Fenge decoction of 1.5 g?kg-1 for 14
      days, the concentrations of Ang II in plasma were significantly lower in F-1 and
      F-2 groups than those in model group (p < 0.01 or p < 0.05), but there were no
      significantly difference in F-3 and F-4 groups than those in model group (p >
      0.05). Despite the molecular aggregation is a common physical phenomenon, it
      influence on the kind and amount of molecule per unit volume. Molecules
      morphology influence on the absorption behavior of drugs in vivo therefore is to
      have an impact on pharmacological function. 

PMID- 26198224
TI  - Relationship of structure and function of DNA-binding domain in vitamin D
      receptor.
AB  - While the structure of the DNA-binding domain (DBD) of the vitamin D receptor
      (VDR) has been determined in great detail, the roles of its domains and how to
      bind the motif of its target genes are still under debate. The VDR DBD consists
      of two zinc finger modules and a C-terminal extension (CTE), at the end of the C
      terminal of each structure presenting alpha-helix. For the first zinc finger
      structure, N37 and S-box take part in forming a dimer with 9-cis retinoid X
      receptor (RXR), while V26, R50, P-box and S-box participate in binding with VDR
      response elements (VDRE). For the second zinc finger structure, P61, F62 and H75
      are essential in the structure of the VDR homodimer with the residues N37, E92
      and F93 of the downstream of partner VDR, which form the inter-DBD interface. T
      box of the CTE, especially the F93 and I94, plays a critical role in
      heterodimerization and heterodimers-VDRE binding. Six essential residues (R102,
      K103, M106, I107, K109, and R110) of the CTE alpha-helix of VDR construct one
      interaction face, which packs against the DBD core of the adjacent symmetry mate.
      In 1,25(OH)2D3-activated signaling, the VDR-RXR heterodimer may bind to DR3-type
      VDRE and ER9-type VDREs of its target gene directly resulting in transactivation
      and also bind to DR3-liked nVDRE of its target gene directly resulting in
      transrepression. Except for this, 1alpha,25(OH)2D3 ligand VDR-RXR may bind to
      1alphanVDRE indirectly through VDIR, resulting in transrepression of the target
      gene. Upon binding of 1alpha,25(OH)2D3, VDR can transactivate and transrepress
      its target genes depending on the DNA motif that DBD binds. 

PMID- 26198225
TI  - Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted
      for Fumarate Respiration of Parasite Mitochondria.
AB  - Recent studies on the respiratory chain of Ascaris suum showed that the
      mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone
      and complex II plays an important role in the anaerobic energy metabolism of
      adult A. suum. The system is the major pathway of energy metabolism for
      adaptation to a hypoxic environment not only in parasitic organisms, but also in
      some types of human cancer cells. Thus, enzymes of the pathway are potential
      targets for chemotherapy. We found that flutolanil is an excellent inhibitor for
      A. suum complex II (IC50 = 0.058 MUM) but less effectively inhibits homologous
      porcine complex II (IC50 = 45.9 MUM). In order to account for the specificity of
      flutolanil to A. suum complex II from the standpoint of structural biology, we
      determined the crystal structures of A. suum and porcine complex IIs binding
      flutolanil and its derivative compounds. The structures clearly demonstrated key
      interactions responsible for its high specificity to A. suum complex II and
      enabled us to find analogue compounds, which surpass flutolanil in both potency
      and specificity to A. suum complex II. Structures of complex IIs binding these
      compounds will be helpful to accelerate structure-based drug design targeted for
      complex IIs. 

PMID- 26198226
TI  - beta-Radiation Stress Responses on Growth and Antioxidative Defense System in
      Plants: A Study with Strontium-90 in Lemna minor.
AB  - In the following study, dose dependent effects on growth and oxidative stress
      induced by beta-radiation were examined to gain better insights in the mode of
      action of beta-radiation induced stress in plant species. Radiostrontium (90Sr)
      was used to test for beta-radiation induced responses in the freshwater
      macrophyte Lemna minor. The accumulation pattern of 90Sr was examined for L.
      minor root and fronds separately over a seven-day time period and was
      subsequently used in a dynamic dosimetric model to calculate beta-radiation dose
      rates. Exposing L. minor plants for seven days to a 90Sr activity concentration
      of 25 up to 25,000 kBq.L-1 resulted in a dose rate between 0.084 +/- 0.004 and 97
      +/- 8 mGy.h-1. After seven days of exposure, root fresh weight showed a dose
      dependent decrease starting from a dose rate of 9.4 +/- 0.5 mGy.h-1. Based on
      these data, an EDR10 value of 1.5 +/- 0.4 mGy.h-1 was estimated for root fresh
      weight and 52 +/- 17 mGy.h-1 for frond fresh weight. Different antioxidative
      enzymes and metabolites were further examined to analyze if beta-radiation
      induces oxidative stress in L. minor.

PMID- 26198227
TI  - Fungi Isolated from Maize (Zea mays L.) Grains and Production of Associated
      Enzyme Activities.
AB  - Filamentous fungi produce a great variety of enzymes, and research on their
      biotechnological potential has recently intensified. The objective of this work
      was to identify, at the species level, using DNA barcoding, 46 fungal isolates
      obtained from maize grains with rot symptoms. We also analyzed the production of
      extracellular amylases, cellulases, proteases and lipases of 33 of those fungal
      isolates. The enzymatic activities were evaluated by the formation of a clear
      halo or a white precipitate around the colonies in defined substrate media. The
      found fungi belong to the genera Talaromyces, Stenocarpella, Penicillium,
      Phlebiopsis, Cladosporium, Hyphopichia, Epicoccum, Trichoderma, Aspergillus,
      Irpex, Fusarium, Microdochium, Mucor and Sarocladium. In the genus Fusarium, the
      species Fusarium verticillioides was predominant and this genus presented the
      highest diversity, followed by the genera Aspergillus. The best genera for lipase
      production were Cladosporium and Penicillium; while Cladosporium, Aspergillus and
      Penicillium were best for cellulase activity; Hyphopichia, Aspergillus and Irpex
      for amylase activity; and Cladosporium and Sarocladium for proteases activity. In
      conclusion, a collection of fungi from maize seeds presenting rotten symptoms
      were obtained, among which exist important producers of hydrolases. 

PMID- 26198229
TI  - An Overview of Practical Applications of Protein Disorder Prediction and Drive
      for Faster, More Accurate Predictions.
AB  - Protein disordered regions are segments of a protein chain that do not adopt a
      stable structure. Thus far, a variety of protein disorder prediction methods have
      been developed and have been widely used, not only in traditional bioinformatics
      domains, including protein structure prediction, protein structure determination
      and function annotation, but also in many other biomedical fields. The
      relationship between intrinsically-disordered proteins and some human diseases
      has played a significant role in disorder prediction in disease identification
      and epidemiological investigations. Disordered proteins can also serve as
      potential targets for drug discovery with an emphasis on the disordered-to
      ordered transition in the disordered binding regions, and this has led to
      substantial research in drug discovery or design based on protein disordered
      region prediction. Furthermore, protein disorder prediction has also been applied
      to healthcare by predicting the disease risk of mutations in patients and
      studying the mechanistic basis of diseases. As the applications of disorder
      prediction increase, so too does the need to make quick and accurate predictions.
      To fill this need, we also present a new approach to predict protein residue
      disorder using wide sequence windows that is applicable on the genomic scale. 

PMID- 26198230
TI  - Phase Difference Optimization of Dual-Wavelength Excitation for the CW
      Photoacoustic-Based Noninvasive and Selective Investigation of Aqueous Solutions
      of Glucose.
AB  - Towards the noninvasive and continuous monitoring of blood glucose levels, we
      chose the continuous-wave photoacoustic (CW-PA) technique and developed the
      optical power balance shift (OPBS) method. However, operating with optical
      wavelengths in the near-infrared (NIR) region ensures deep penetration inside
      human soft-tissue, but also leads to two serious issues: strong background level
      noise from water molecules in this wavelength range and small differences between
      the absorbance spectra of diluted compounds. To resolve them, the OPBS method
      relies on simultaneous optical excitation at two wavelengths for differential
      measurements. However, the first validation in vitro with calibrated aqueous
      solutions of glucose and albumin revealed strong dependence on the phase
      difference between the two lights sources. In this paper, we report a systematic
      investigation of this parameter, from PA-based measurements over a wide range of
      phase differences and an extensive characterization in the frequency domain. The
      process of maintaining the phase quadrature of the two optical signals is
      demonstrated in real time through an analysis of the PA signal and therefore does
      not require any additional equipment. Finally, a comparison of aqueous glucose
      solution characterizations at high concentration levels with the two methods was
      performed and consistent results were obtained. 

PMID- 26198231
TI  - Instantaneous Respiratory Estimation from Thoracic Impedance by Empirical Mode
      Decomposition.
AB  - Impedance plethysmography provides a way to measure respiratory activity by
      sensing the change of thoracic impedance caused by inspiration and expiration.
      This measurement imposes little pressure on the body and uses the human body as
      the sensor, thereby reducing the need for adjustments as body position changes
      and making it suitable for long-term or ambulatory monitoring. The empirical mode
      decomposition (EMD) can decompose a signal into several intrinsic mode functions
      (IMFs) that disclose nonstationary components as well as stationary components
      and, similarly, capture respiratory episodes from thoracic impedance. However,
      upper-body movements usually produce motion artifacts that are not easily removed
      by digital filtering. Moreover, large motion artifacts disable the EMD to
      decompose respiratory components. In this paper, motion artifacts are detected
      and replaced by the data mirrored from the prior and the posterior before EMD
      processing. A novel intrinsic respiratory reconstruction index that considers
      both global and local properties of IMFs is proposed to define respiration
      related IMFs for respiration reconstruction and instantaneous respiratory
      estimation. Based on the experiments performing a series of static and dynamic
      physical activates, our results showed the proposed method had higher cross
      correlations between respiratory frequencies estimated from thoracic impedance
      and those from oronasal airflow based on small window size compared to the
      Fourier transform-based method. 

PMID- 26198228
TI  - Epigenetic and Posttranslational Modifications in Light Signal Transduction and
      the Circadian Clock in Neurospora crassa.
AB  - Blue light, a key abiotic signal, regulates a wide variety of physiological
      processes in many organisms. One of these phenomena is the circadian rhythm
      presents in organisms sensitive to the phase-setting effects of blue light and
      under control of the daily alternation of light and dark. Circadian clocks
      consist of autoregulatory alternating negative and positive feedback loops
      intimately connected with the cellular metabolism and biochemical processes.
      Neurospora crassa provides an excellent model for studying the molecular
      mechanisms involved in these phenomena. The White Collar Complex (WCC), a blue
      light receptor and transcription factor of the circadian oscillator, and
      Frequency (FRQ), the circadian clock pacemaker, are at the core of the Neurospora
      circadian system. The eukaryotic circadian clock relies on
      transcriptional/translational feedback loops: some proteins rhythmically repress
      their own synthesis by inhibiting the activity of their transcriptional factors,
      generating self-sustained oscillations over a period of about 24 h. One of the
      basic mechanisms that perpetuate self-sustained oscillations is post translation
      modification (PTM). The acronym PTM generically indicates the addition of acetyl,
      methyl, sumoyl, or phosphoric groups to various types of proteins. The protein
      can be regulatory or enzymatic or a component of the chromatin. PTMs influence
      protein stability, interaction, localization, activity, and chromatin packaging.
      Chromatin modification and PTMs have been implicated in regulating circadian
      clock function in Neurospora. Research into the epigenetic control of
      transcription factors such as WCC has yielded new insights into the temporal
      modulation of light-dependent gene transcription. Here we report on epigenetic
      and protein PTMs in the regulation of the Neurospora crassa circadian clock. We
      also present a model that illustrates the molecular mechanisms at the basis of
      the blue light control of the circadian clock. 

PMID- 26198232
TI  - PARAFAC Decomposition for Ultrasonic Wave Sensing of Fiber Bragg Grating Sensors:
      Procedure and Evaluation.
AB  - Ultrasonic wave-sensing technology has been applied for the health monitoring of
      composite structures, using normal fiber Bragg grating (FBG) sensors with a high
      speed wavelength interrogation system of arrayed waveguide grating (AWG) filters;
      however, researchers are required to average thousands of repeated measurements
      to distinguish significant signals. To resolve this bottleneck problem, this
      study established a signal-processing strategy that improves the signal-to-noise
      ratio for the one-time measured signal of ultrasonic waves, by application of
      parallel factor analysis (PARAFAC) technology that produces unique multiway
      decomposition without additional orthogonal or independent constraints. Through
      bandpass processing of the AWG filter and complex wavelet transforms, ultrasonic
      wave signals are preprocessed as time, phase, and frequency profiles, and then
      decomposed into a series of conceptual three-way atoms by PARAFAC. While an
      ultrasonic wave results in a Bragg wavelength shift, antiphase fluctuations can
      be observed at two adjacent AWG ports. Thereby, concentrating on antiphase
      features among the three-way atoms, a fitting atom can be chosen and then
      restored to three-way profiles as a final result. An experimental study has
      revealed that the final result is consistent with the conventional 1024-data
      averaging signal, and relative error evaluation has indicated that the signal-to
      noise ratio of ultrasonic waves can be significantly improved. 

PMID- 26198233
TI  - An Autonomous Star Identification Algorithm Based on One-Dimensional Vector
      Pattern for Star Sensors.
AB  - In order to enhance the robustness and accelerate the recognition speed of star
      identification, an autonomous star identification algorithm for star sensors is
      proposed based on the one-dimensional vector pattern (one_DVP). In the proposed
      algorithm, the space geometry information of the observed stars is used to form
      the one-dimensional vector pattern of the observed star. The one-dimensional
      vector pattern of the same observed star remains unchanged when the stellar image
      rotates, so the problem of star identification is simplified as the comparison of
      the two feature vectors. The one-dimensional vector pattern is adopted to build
      the feature vector of the star pattern, which makes it possible to identify the
      observed stars robustly. The characteristics of the feature vector and the
      proposed search strategy for the matching pattern make it possible to achieve the
      recognition result as quickly as possible. The simulation results demonstrate
      that the proposed algorithm can effectively accelerate the star identification.
      Moreover, the recognition accuracy and robustness by the proposed algorithm are
      better than those by the pyramid algorithm, the modified grid algorithm, and the
      LPT algorithm. The theoretical analysis and experimental results show that the
      proposed algorithm outperforms the other three star identification algorithms. 

PMID- 26198234
TI  - Bioactive 7-Oxabicyclic[6.3.0]lactam and 12-Membered Macrolides from a Gorgonian
      Derived Cladosporium sp. Fungus.
AB  - One new bicyclic lactam, cladosporilactam A (1), and six known 12-membered
      macrolides (2-7) were isolated from a gorgonian-derived Cladosporium sp. fungus
      collected from the South China Sea. Their complete structural assignments were
      elucidated by comprehensive spectroscopic investigation. Quantum chemistry
      calculations were used in support of the structural determination of 1. The
      absolute configuration of 1 was determined by calculation of its optical
      rotation. Cladosporilactam A (1) was the first example of 7
      oxabicyclic[6.3.0]lactam obtained from a natural source. Compound 1 exhibited
      promising cytotoxic activity against cervical cancer HeLa cell line with an IC50
      value of 0.76 MUM. 

PMID- 26198236
TI  - Red Algae (Rhodophyta) from the Coast of Madagascar: Preliminary Bioactivity
      Studies and Isolation of Natural Products.
AB  - Several species of red algae (Rhodophyta) from the coastal regions of Madagascar
      have been investigated for their natural products. The most abundant compound was
      cholesterol (5) in combination with a series of oxidized congeners. The
      brominated indoles 1-3 along with the sesquiterpene debilone (4) have been
      isolated from Laurencia complanata. For the first time, debilone (4) has been
      obtained from a marine plant. From the methanol extract of Calloseris sp., we
      have achieved the second isolation of the unusual A-ring contracted steroids (-)
      2-ethoxycarbonyl-2beta-hydroxy-A-nor-cholest-5-en-4-one (9) and phorbasterone B
      (10). The crude extracts of Laurencia complanata exhibited antimicrobial activity
      against Bacillus cereus, Staphylococcus aureus, Streptococcus pneumoniae, and
      Candida albicans. 

PMID- 26198235
TI  - Functional and Structural Characterization of FAU Gene/Protein from Marine Sponge
      Suberites domuncula.
AB  - Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV) ubiquitously expressed (FAU)
      gene is down-regulated in human prostate, breast and ovarian cancers. Moreover,
      its dysregulation is associated with poor prognosis in breast cancer. Sponges
      (Porifera) are animals without tissues which branched off first from the common
      ancestor of all metazoans. A large majority of genes implicated in human cancers
      have their homologues in the sponge genome. Our study suggests that FAU gene from
      the sponge Suberites domuncula reflects characteristics of the FAU gene from the
      metazoan ancestor, which have changed only slightly during the course of animal
      evolution. We found pro-apoptotic activity of sponge FAU protein. The same as its
      human homologue, sponge FAU increases apoptosis in human HEK293T cells. This
      indicates that the biological functions of FAU, usually associated with "higher"
      metazoans, particularly in cancer etiology, possess a biochemical background
      established early in metazoan evolution. The ancestor of all animals possibly
      possessed FAU protein with the structure and function similar to evolutionarily
      more recent versions of the protein, even before the appearance of true tissues
      and the origin of tumors and metastasis. It provides an opportunity to use pre
      bilaterian animals as a simpler model for studying complex interactions in human
      cancerogenesis. 

PMID- 26198237
TI  - Structure and Effects of Cyanobacterial Lipopolysaccharides.
AB  - Lipopolysaccharide (LPS) is a component of the outer membrane of mainly Gram
      negative bacteria and cyanobacteria. The LPS molecules from marine and
      terrestrial bacteria show structural variations, even among strains within the
      same species living in the same environment. Cyanobacterial LPS has a unique
      structure, since it lacks heptose and 3-deoxy-d-manno-octulosonic acid (also
      known as keto-deoxyoctulosonate (KDO)), which are present in the core region of
      common Gram-negative LPS. In addition, the cyanobacterial lipid A region lacks
      phosphates and contains odd-chain hydroxylated fatty acids. While the role of
      Gram-negative lipid A in the regulation of the innate immune response through
      Toll-like Receptor (TLR) 4 signaling is well characterized, the role of the
      structurally different cyanobacterial lipid A in TLR4 signaling is not well
      understood. The uncontrolled inflammatory response of TLR4 leads to autoimmune
      diseases such as sepsis, and thus the less virulent marine cyanobacterial LPS
      molecules can be effective to inhibit TLR4 signaling. This review highlights the
      structural comparison of LPS molecules from marine cyanobacteria and Gram
      negative bacteria. We discuss the potential use of marine cyanobacterial LPS as a
      TLR4 antagonist, and the effects of cyanobacterial LPS on humans and marine
      organisms. 

PMID- 26198238
TI  - Indoor Particulate Matter Concentration, Water Boiling Time, and Fuel Use of
      Selected Alternative Cookstoves in a Home-Like Setting in Rural Nepal.
AB  - Alternative cookstoves are designed to improve biomass fuel combustion efficiency
      to reduce the amount of fuel used and lower emission of air pollutants. The Nepal
      Cookstove Trial (NCT) studies effects of alternative cookstoves on family health.
      Our study measured indoor particulate matter concentration (PM2.5), boiling time,
      and fuel use of cookstoves during a water-boiling test in a house-like setting in
      rural Nepal. Study I was designed to select a stove to be used in the NCT; Study
      II evaluated stoves used in the NCT. In Study I, mean indoor PM2.5 using wood
      fuel was 4584 MUg/m3, 1657 MUg/m3, and 2414 MUg/m3 for the traditional,
      alternative mud brick stove (AMBS-I) and Envirofit G-series, respectively. The
      AMBS-I reduced PM2.5 concentration but increased boiling time compared to the
      traditional stove (p-values < 0.001). Unlike AMBS-I, Envirofit G-series did not
      significantly increase overall fuel consumption. In Phase II, the manufacturer
      altered Envirofit stove (MAES) and Nepal Nutrition Intervention Project Sarlahi
      (NNIPS) altered Envirofit stove (NAES), produced lower mean PM2.5, 1573 MUg/m3
      and 1341 MUg/m3, respectively, relative to AMBS-II 3488 MUg/m3 for wood tests.
      The liquid propane gas stove had the lowest mean PM2.5 concentrations, with
      measurements indistinguishable from background levels. Results from Study I and
      II showed significant reduction in PM2.5 for all alternative stoves in a
      controlled setting. In study I, the AMBS-I stove required more fuel than the
      traditional stove. In contrast, in study II, the MAES and NAES stoves required
      statistically less fuel than the AMBS-II. Reductions and increases in fuel use
      should be interpreted with caution because the composition of fuels was not
      standardized--an issue which may have implications for generalizability of other
      findings as well. Boiling times for alternative stoves in Study I were
      significantly longer than the traditional stove--a trade-off that may have
      implications for acceptability of the stoves among end users. These extended
      cooking times may increase cumulative exposure during cooking events where
      emission rates are lower; these differences must be carefully considered in the
      evaluation of alternative stove designs.

PMID- 26198239
TI  - Seminal Shedding of CMV and HIV Transmission among Men Who Have Sex with Men.
AB  - As in many urban areas in the United States, the largest burden of the HIV
      epidemic in San Diego is borne by men who have sex with men (MSM). Using data
      from well-characterized HIV transmitting and non-transmitting partner pairs of
      MSM in San Diego, we calculated the population attributable risk (PAR) of HIV
      transmissions for different co-infections common among MSM in this area. We found
      that over a third of HIV transmissions could be potentially attributed to genital
      shedding of cytomegalovirus (CMV) (111 transmission events), compared to 21%
      potentially attributed to bacterial sexually transmitted infections (STI) (62
      events) and 17% to herpes simplex virus type-2 (HSV-2) (51 events). Although our
      study cannot infer causality between the described associations and is limited in
      sample size, these results suggest that interventions aimed at reducing CMV
      shedding might be an attractive HIV prevention strategy in populations with high
      prevalence of CMV co-infection. 

PMID- 26198241
TI  - Ultra Deep Sequencing of a Baculovirus Population Reveals Widespread Genomic
      Variations.
AB  - Viruses rely on widespread genetic variation and large population size for
      adaptation. Large DNA virus populations are thought to harbor little variation
      though natural populations may be polymorphic. To measure the genetic variation
      present in a dsDNA virus population, we deep sequenced a natural strain of the
      baculovirus Autographa californica multiple nucleopolyhedrovirus. With 124,221X
      average genome coverage of our 133,926 bp long consensus, we could detect low
      frequency mutations (0.025%). K-means clustering was used to classify the
      mutations in four categories according to their frequency in the population. We
      found 60 high frequency non-synonymous mutations under balancing selection
      distributed in all functional classes. These mutants could alter viral adaptation
      dynamics, either through competitive or synergistic processes. Lastly, we
      developed a technique for the delimitation of large deletions in next generation
      sequencing data. We found that large deletions occur along the entire viral
      genome, with hotspots located in homologous repeat regions (hrs). Present in
      25.4% of the genomes, these deletion mutants presumably require functional
      complementation to complete their infection cycle. They might thus have a large
      impact on the fitness of the baculovirus population. Altogether, we found a wide
      breadth of genomic variation in the baculovirus population, suggesting it has
      high adaptive potential. 

PMID- 26198240
TI  - Modes of Human T Cell Leukemia Virus Type 1 Transmission, Replication and
      Persistence.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes cancer
      (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly HTLV
      associated myelopathy-tropical spastic paraparesis, HAM/TSP). Since virions are
      particularly unstable, HTLV-1 transmission primarily occurs by transfer of a cell
      carrying an integrated provirus. After transcription, the viral genomic RNA
      undergoes reverse transcription and integration into the chromosomal DNA of a
      cell from the newly infected host. The virus then replicates by either one of two
      modes: (i) an infectious cycle by virus budding and infection of new targets and
      (ii) mitotic division of cells harboring an integrated provirus. HTLV-1
      replication initiates a series of mechanisms in the host including antiviral
      immunity and checkpoint control of cell proliferation. HTLV-1 has elaborated
      strategies to counteract these defense mechanisms allowing continuous persistence
      in humans. 

PMID- 26198242
TI  - Early Events in Chikungunya Virus Infection-From Virus Cell Binding to Membrane
      Fusion.
AB  - Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne alphavirus causing
      millions of infections in the tropical and subtropical regions of the world.
      CHIKV infection often leads to an acute self-limited febrile illness with
      debilitating myalgia and arthralgia. A potential long-term complication of CHIKV
      infection is severe joint pain, which can last for months to years. There are no
      vaccines or specific therapeutics available to prevent or treat infection. This
      review describes the critical steps in CHIKV cell entry. We summarize the latest
      studies on the virus-cell tropism, virus-receptor binding, internalization,
      membrane fusion and review the molecules and compounds that have been described
      to interfere with virus cell entry. The aim of the review is to give the reader a
      state-of-the-art overview on CHIKV cell entry and to provide an outlook on
      potential new avenues in CHIKV research. 

PMID- 26198243
TI  - Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses.
AB  - Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated
      genes (ISGs). However, only a selection of their products have been demonstrated
      to be responsible for the inhibition of rhabdovirus replication in cultured
      cells; and only a few have been shown to play a role in mediating the antiviral
      response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus
      replication at different stages via the induction of a variety of ISGs. This
      review will discuss how individual ISG products confer resistance to
      rhabdoviruses by blocking viral entry, degrading single stranded viral RNA,
      inhibiting viral translation or preventing release of virions from the cell.
      Furthermore, this review will highlight how these viruses counteract the host IFN
      system. 

PMID- 26198244
TI  - Resistance against Integrase Strand Transfer Inhibitors and Relevance to HIV
      Persistence.
AB  - Drug resistance prevents the successful treatment of HIV-positive individuals by
      decreasing viral sensitivity to a drug or a class of drugs. In addition to
      transmitted resistant viruses, treatment-naive individuals can be confronted with
      the problem of drug resistance through de novo emergence of such variants.
      Resistant viruses have been reported for every antiretroviral drug tested so far,
      including the integrase strand transfer inhibitors raltegravir, elvitegravir and
      dolutegravir. However, de novo resistant variants against dolutegravir have been
      found in treatment-experienced but not in treatment-naive individuals, a
      characteristic that is unique amongst antiretroviral drugs. We review here the
      issue of drug resistance against integrase strand transfer inhibitors as well as
      both pre-clinical and clinical studies that have led to the identification of the
      R263K mutation in integrase as a signature resistance substitution for
      dolutegravir. We also discuss how the topic of drug resistance against integrase
      strand transfer inhibitors may have relevance in regard to the nature of the HIV
      reservoir and possible HIV curative strategies. 

PMID- 26198245
TI  - Epigallocatechin Gallate: A Review of Its Beneficial Properties to Prevent
      Metabolic Syndrome.
AB  - Obesity and being overweight are linked with a cluster of metabolic and vascular
      disorders that have been termed the metabolic syndrome. This syndrome promotes
      the incidence of cardiovascular diseases that are an important public health
      problem because they represent a major cause of death worldwide. Whereas there is
      not a universally-accepted set of diagnostic criteria, most expert groups agree
      that this syndrome is defined by an endothelial dysfunction, an impaired insulin
      sensitivity and hyperglycemia, dyslipidemia, abdominal obesity and hypertension.
      Epidemiological studies suggest that the beneficial cardiovascular health effects
      of diets rich in green tea are, in part, mediated by their flavonoid content,
      with particular benefits provided by members of this family such as
      epigallocatechin gallate (EGCG). Although their bioavailability is discussed,
      various studies suggest that EGCG modulates cellular and molecular mechanisms of
      various symptoms leading to metabolic syndrome. Therefore, according to in vitro
      and in vivo model data, this review attempts to increase our understanding about
      the beneficial properties of EGCG to prevent metabolic syndrome. 

PMID- 26198247
TI  - The Reliability and Validity of the Perceived Dietary Adherence Questionnaire for
      People with Type 2 Diabetes.
AB  - Nutrition therapy is essential for diabetes treatment, and assessment of dietary
      intake can be time consuming. The purpose of this study was to develop a reliable
      and valid instrument to measure diabetic patients' adherence to Canadian diabetes
      nutrition recommendations. Specific information derived from three, repeated 24-h
      dietary recalls of 64 type 2 diabetic patients, aged 59.2 +/- 9.7 years, was
      correlated with a total score and individual items of the Perceived Dietary
      Adherence Questionnaire (PDAQ). Test-retest reliability was completed by 27 type
      2 diabetic patients, aged 62.8 +/- 8.4 years. The correlation coefficients for
      PDAQ items versus 24-h recalls ranged from 0.46 to 0.11. The intra-class
      correlation (0.78) was acceptable, indicating good reliability. The results
      suggest that PDAQ is a valid and reliable measure of diabetes nutrition
      recommendations. Because it is quick to administer and score, it may be useful as
      a screening tool in research and as a clinical tool to monitor dietary adherence.

PMID- 26198246
TI  - Anti-Diabetic and Hepato-Renal Protective Effects of Ziyuglycoside II Methyl
      Ester in Type 2 Diabetic Mice.
AB  - Type 2 diabetes is a metabolic disorder caused by abnormal carbohydrate
      metabolism, and closely associated with abnormal lipid metabolism and hepato
      renal dysfunction. This study investigated the anti-diabetic and hepato-renal
      protective properties of ziyuglycoside I (ZG01) derivative on type 2 diabetes.
      ZG01 was isolated from roots of Sanguisorba officinalis and chemically modified
      by deglycosylation and esterification to obtained ziyuglycoside II methyl ester
      (ZG02-ME). Here, we showed that ZG02-ME has stronger anti-diabetic activity than
      the original compound (ZG01) through decreasing blood glucose, glycated
      hemoglobin (HbA1c), and insulin levels in a mouse model of type 2 diabetes (db/db
      mice). We further found that ZG02-ME treatment effectively ameliorated serum
      insulin, leptin and C-peptide levels, which are key metabolic hormones, in db/db
      mice. In addition, we showed that elevated basal blood lipid levels were
      decreased by ZG02-ME treatment in db/db mice. Furthermore, treatment of ZG02-ME
      significantly decreased serum AST, ALT, BUN, creatinine, and liver lipid
      peroxidation in db/db mice. These results demonstrated that compared to ZG01,
      chemically modified ZG02-ME possess improved anti-diabetic properties, and has
      hepato-renal protective activities in type 2 diabetes. 

PMID- 26198248
TI  - A Dietary Pattern Derived by Reduced Rank Regression is Associated with Type 2
      Diabetes in An Urban Ghanaian Population.
AB  - Reduced rank regression (RRR) is an innovative technique to establish dietary
      patterns related to biochemical risk factors for type 2 diabetes, but has not
      been applied in sub-Saharan Africa. In a hospital-based case-control study for
      type 2 diabetes in Kumasi (diabetes cases, 538; controls, 668) dietary intake was
      assessed by a specific food frequency questionnaire. After random split of our
      study population, we derived a dietary pattern in the training set using RRR with
      adiponectin, HDL-cholesterol and triglycerides as responses and 35 food items as
      predictors. This pattern score was applied to the validation set, and its
      association with type 2 diabetes was examined by logistic regression. The dietary
      pattern was characterized by a high consumption of plantain, cassava, and garden
      egg, and a low intake of rice, juice, vegetable oil, eggs, chocolate drink,
      sweets, and red meat; the score correlated positively with serum triglycerides
      and negatively with adiponectin. The multivariate-adjusted odds ratio of type 2
      diabetes for the highest quintile compared to the lowest was 4.43 (95% confidence
      interval: 1.87-10.50, p for trend < 0.001). The identified dietary pattern
      increases the odds of type 2 diabetes in urban Ghanaians, which is mainly
      attributed to increased serum triglycerides. 

PMID- 26198249
TI  - Claudin11 Promoter Hypermethylation Is Frequent in Malignant Melanoma of the
      Skin, but Uncommon in Nevus Cell Nevi.
AB  - Epigenetic inactivation of tumor-related genes is an important characteristic in
      the pathology of human cancers, including melanomagenesis. We analyzed the
      epigenetic inactivation of Claudin 11 (CLDN11) in malignant melanoma (MM) of the
      skin, including six melanoma cell lines, 39 primary melanoma, 41 metastases of MM
      and 52 nevus cell nevi (NCN). CLDN11 promoter hypermethylation was found in 19
      out of 39 (49%) of the primary MM and in 21 out of 41 (51%) of the MM metastases,
      but only in eight out of 52 (15%) of NCN (p = 0.001 and p = 0.0003,
      respectively). Moreover, a significant increase in the methylation level of
      CLDN11 from primary melanomas to MM metastases was revealed (p = 0.003).
      Methylation of CLDN11 was significantly more frequent in skin metastases (79%)
      compared to brain metastases (31%; p = 0.007). CLDN11 methylation was also found
      in five out of six MM cell lines (83%) and its promoter hypermethylation
      correlated with a reduced expression. Treatment of MM cell lines with a DNA
      methylation inhibitor reactivated CLDN11 transcription by its promoter
      demethylation. In summary, CLDN11 proved to be an epigenetically inactivated
      tumor related gene in melanomagenesis, and analysis of CLDN11 methylation level
      represents a potential tool for assisting in the discrimination between malignant
      melanoma and nevus cell nevi. 

PMID- 26198250
TI  - Molecular and Cellular Mechanisms of Action of Tumour Suppressor GAS5 LncRNA.
AB  - It is increasingly recognised that lncRNAs play essential regulatory roles in
      fundamental biological processes and, consequently, that their dysregulation may
      contribute to major human diseases, including cancer. Better understanding of
      lncRNA biology may therefore offer new insights into pathogenetic mechanisms and
      thereby offer novel opportunities for diagnosis and therapy. Of particular
      interest in this regard is GAS5 lncRNA, which is down-regulated in multiple
      cancers, with expression levels related to both clinico-pathological
      characteristics and patient prognosis. Functional studies have further shown that
      GAS5 lncRNA both inhibits the proliferation and promotes the apoptosis of
      multiple cell types, and that together these cellular mechanisms of action are
      likely to form the basis of its tumour suppressor action. At the same time,
      advances have been made in our understanding of the molecular mechanisms of GAS5
      lncRNA action in recent years, including riborepression of certain steroid
      hormone receptors and sequestration of miR-21, impacting key regulatory pathways
      of cell survival. Overall this accumulating knowledge has the potential to
      improve both the diagnosis and treatment of cancer, and ultimately patient
      outcome. 

PMID- 26198252
TI  - Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the
      performance of HRP2-based malaria rapid diagnostic test.
AB  - BACKGROUND: The genetic variation in the Plasmodium falciparum histidine-rich
      protein 2 (pfhrp2) gene that may compromise the use of pfhrp2-based rapid
      diagnostic tests (RDTs) for the diagnosis of malaria was assessed in P.
      falciparum isolates from Yemen. METHODS: This study was conducted in Hodeidah and
      Al-Mahwit governorates, Yemen. A total of 622 individuals with fever were
      examined for malaria by CareStart malaria HRP2-RDT and Giemsa-stained thin and
      thick blood films. The Pfhrp2 gene was amplified and sequenced from 180 isolates,
      and subjected to amino acid repeat types analysis. RESULTS: A total of 188
      (30.2%) participants were found positive for P. falciparum by the RDT. Overall,
      12 different amino acid repeat types were identified in Yemeni isolates. Six
      repeat types were detected in all the isolates (100%) namely types 1, 2, 6, 7, 10
      and 12 while types 9 and 11 were not detected in any of the isolates. Moreover,
      the sensitivity and specificity of the used PfHRP2-based RDTs were high (90.5%
      and 96.1%, respectively). CONCLUSION: The present study provides data on the
      genetic variation within the pfhrp2 gene, and its potential impact on the PfHRP2
      based RDTs commonly used in Yemen. CareStart Malaria HRP2-based RDT showed high
      sensitivity and specificity in endemic areas of Yemen.

PMID- 26198251
TI  - Characterization of Lactate Sensors Based on Lactate Oxidase and Palladium
      Benzoporphyrin Immobilized in Hydrogels.
AB  - An optical biosensor for lactate detection is described. By encapsulating enzyme
      phosphor sensing molecules within permeable hydrogel materials, lactate-sensitive
      emission lifetimes were achieved. The relative amount of monomer was varied to
      compare three homo- and co-polymer materials: poly(2-hydroxyethyl methacrylate)
      (pHEMA) and two copolymers of pHEMA and poly(acrylamide) (pAam). Diffusion
      analysis demonstrated the ability to control lactate transport by varying the
      hydrogel composition, while having a minimal effect on oxygen diffusion. Sensors
      displayed the desired dose-variable response to lactate challenges, highlighting
      the tunable, diffusion-controlled nature of the sensing platform. Short-term
      repeated exposure tests revealed enhanced stability for sensors comprising
      hydrogels with acrylamide additives; after an initial "break-in" period, signal
      retention was 100% for 15 repeated cycles. Finally, because this study describes
      the modification of a previously developed glucose sensor for lactate analysis,
      it demonstrates the potential for mix-and-match enzyme-phosphor-hydrogel sensing
      for use in future multi-analyte sensors. 

PMID- 26198253
TI  - Noninvasive vascular imaging of ruptured retinal arterial macroaneurysms by
      Doppler optical coherence tomography.
AB  - BACKGROUND: To describe Doppler optical coherence tomography (OCT) imaging of
      ruptured retinal arterial macroaneurysms (RAMs). METHODS: Four eyes of four
      patients with ruptured RAMs were prospectively studied. Vascular imaging was
      obtained using swept-source Doppler OCT, and compared with indocyanine green
      angiography images. RESULTS: En face projection of Doppler OCT images clearly
      showed RAMs at the corresponding locations of lesions in the indocyanine green
      angiography images. In Doppler OCT images, RAMs were located in the inner retina
      in three eyes and in the medium layer of the retina in one eye. In one eye,
      detection of RAMs by standard OCT was difficult because of the presence of inner
      retinal hemorrhage. In one eye, disappearance of blood flow after direct laser
      photocoagulation could be confirmed by Doppler OCT images. CONCLUSIONS: Doppler
      OCT imaging may potentially function as a noninvasive complementary procedure
      with indocyanine green angiography.

PMID- 26198254
TI  - Erwinia iniecta sp. nov., isolated from Russian wheat aphid (Diuraphis noxia).
AB  - Short, Gram-negative-staining, rod-shaped bacteria were isolated from crushed
      bodies of Russian wheat aphid [Diuraphis noxia (Kurdjumov)] and artificial diets
      after Russian wheat aphid feeding. Based on multilocus sequence analysis
      involving the 16S rRNA, atpD, infB, gyrB and rpoB genes, these bacterial isolates
      constitute a novel clade in the genus Erwinia, and were most closely related to
      Erwinia toletana. Representative distinct strains within this clade were used for
      comparisons with related species of Erwinia. Phenotypic comparisons using four
      distinct strains and average nucleotide identity (ANI) measurements using two
      distinct draft genomes revealed that these strains form a novel species within
      the genus Erwinia. The name Erwinia iniecta sp. nov. is proposed, and strain
      B120T ( = CFBP 8182T = NCCB 100485T) was designated the type strain. Erwinia
      iniecta sp. nov. was not pathogenic to plants. However, virulence to the Russian
      wheat aphid was observed.

PMID- 26198255
TI  - Neurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery
      into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model
      of early Parkinson's disease.
AB  - BACKGROUND: The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) influences
      nigral dopaminergic neurons via autocrine and paracrine mechanisms. The reduction
      of BDNF expression in Parkinson's disease substantia nigra (SN) might contribute
      to the death of dopaminergic neurons because inhibiting BDNF expression in the SN
      causes parkinsonism in the rat. This study aimed to demonstrate that increasing
      BDNF expression in dopaminergic neurons of rats with one week of 6
      hydroxydopamine lesion recovers from parkinsonism. The plasmids phDAT-BDNF-flag
      and phDAT-EGFP, coding for enhanced green fluorescent protein, were transfected
      using neurotensin (NTS)-polyplex, which enables delivery of genes into the
      dopaminergic neurons via neurotensin-receptor type 1 (NTSR1) internalization.
      RESULTS: Two weeks after transfections, RT-PCR and immunofluorescence techniques
      showed that the residual dopaminergic neurons retain NTSR1 expression and
      susceptibility to be transfected by the NTS-polyplex. phDAT-BDNF-flag
      transfection did not increase dopaminergic neurons, but caused 7-fold increase in
      dopamine fibers within the SN and 5-fold increase in innervation and dopamine
      levels in the striatum. These neurotrophic effects were accompanied by a
      significant improvement in motor behavior. CONCLUSIONS: NTS-polyplex-mediated
      BDNF overexpression in dopaminergic neurons has proven to be effective to remit
      hemiparkinsonism in the rat. This BDNF gene therapy might be helpful in the early
      stage of Parkinson's disease.

PMID- 26198256
TI  - Cell Type-Specific Gene Expression Analyses by RNA Sequencing Reveal Local High
      Nitrate-Triggered Lateral Root Initiation in Shoot-Borne Roots of Maize by
      Modulating Auxin-Related Cell Cycle Regulation.
AB  - Plants have evolved a unique plasticity of their root system architecture to
      flexibly exploit heterogeneously distributed mineral elements from soil. Local
      high concentrations of nitrate trigger lateral root initiation in adult shoot
      borne roots of maize (Zea mays) by increasing the frequency of early divisions of
      phloem pole pericycle cells. Gene expression profiling revealed that, within 12 h
      of local high nitrate induction, cell cycle activators (cyclin-dependent kinases
      and cyclin B) were up-regulated, whereas repressors (Kip-related proteins) were
      down-regulated in the pericycle of shoot-borne roots. In parallel, a ubiquitin
      protein ligase S-Phase Kinase-Associated Protein1-cullin-F-box protein(S-Phase
      Kinase-Associated Protein 2B)-related proteasome pathway participated in cell
      cycle control. The division of pericycle cells was preceded by increased levels
      of free indole-3-acetic acid in the stele, resulting in DR5-red fluorescent
      protein-marked auxin response maxima at the phloem poles. Moreover, laser-capture
      microdissection-based gene expression analyses indicated that, at the same time,
      a significant local high nitrate induction of the monocot-specific PIN-FORMED9
      gene in phloem pole cells modulated auxin efflux to pericycle cells. Time
      dependent gene expression analysis further indicated that local high nitrate
      availability resulted in PIN-FORMED9-mediated auxin efflux and subsequent cell
      cycle activation, which culminated in the initiation of lateral root primordia.
      This study provides unique insights into how adult maize roots translate
      information on heterogeneous nutrient availability into targeted root
      developmental responses. 

PMID- 26198259
TI  - Synthesis of a flexible macrocyclic tetraimidazolium salt-precursor for a
      tetracarbene ligand with metal dependent coordination modes.
AB  - The cyclic tetraimidazolium salt (H4-)(PF6)4 with flexible linkers between the
      imidazolium groups has been synthesized following a stepwise synthetic approach.
      In situ deprotonation of (H4-)(PF6)4 in the presence of different metal ions
      leads to complexes where the tetracarbene ligand shows differing coordination
      modes depending on the metal center. Due to its high flexibility the tetracarbene
      ligand folds around d(8) transition metal ions such as Ni(II), Pd(II) and Pt(II)
      to yield mononuclear tetracarbene complexes of type [M()](PF6)2 featuring a
      square-planar coordinated metal center. Reaction of with metal centers that
      prefer a linear coordination mode such as Ag(I) yields the tetranuclear silver(i)
      octacarbene complex [Ag4()2](PF6)4 featuring four silver(i) ions sandwiched in
      between two tetra-NHC ligands. 

PMID- 26198257
TI  - Calcineurin B-Like Protein-Interacting Protein Kinase CIPK21 Regulates Osmotic
      and Salt Stress Responses in Arabidopsis.
AB  - The role of calcium-mediated signaling has been extensively studied in plant
      responses to abiotic stress signals. Calcineurin B-like proteins (CBLs) and CBL
      interacting protein kinases (CIPKs) constitute a complex signaling network acting
      in diverse plant stress responses. Osmotic stress imposed by soil salinity and
      drought is a major abiotic stress that impedes plant growth and development and
      involves calcium-signaling processes. In this study, we report the functional
      analysis of CIPK21, an Arabidopsis (Arabidopsis thaliana) CBL-interacting protein
      kinase, ubiquitously expressed in plant tissues and up-regulated under multiple
      abiotic stress conditions. The growth of a loss-of-function mutant of CIPK21,
      cipk21, was hypersensitive to high salt and osmotic stress conditions. The
      calcium sensors CBL2 and CBL3 were found to physically interact with CIPK21 and
      target this kinase to the tonoplast. Moreover, preferential localization of
      CIPK21 to the tonoplast was detected under salt stress condition when coexpressed
      with CBL2 or CBL3. These findings suggest that CIPK21 mediates responses to salt
      stress condition in Arabidopsis, at least in part, by regulating ion and water
      homeostasis across the vacuolar membranes. 

PMID- 26198260
TI  - Depressive Symptoms and Social Support in Adolescents With Type 2 Diabetes.
AB  - INTRODUCTION: Disease management outcomes, depressive symptoms, and levels of
      social support may differ between early and middle adolescents. The purpose of
      this study was to explore the relationships between depressive symptomatology,
      perceived social support, body mass index, hemoglobin A1c (A1C), and months since
      diagnosis for adolescents with type 2 diabetes ages 13 to 17 years. METHODS: This
      cross-sectional, descriptive, correlational study surveyed adolescents at an
      endocrinology clinic regarding depressive symptoms and perceived social support.
      RESULTS: Depressive symptoms were not significantly related to other variables;
      however, mean depressive symptoms scores were higher among early adolescents.
      Middle adolescents had lower body mass index percentiles but higher A1C levels.
      Early adolescents had greater mean scores of social support and reported that
      this support was more important compared with middle adolescents. DISCUSSION: The
      results show that differences exist in perceived social support, depressive
      symptoms, and A1C levels among early and middle adolescents.

PMID- 26198258
TI  - Mapping of a Cellulose-Deficient Mutant Named dwarf1-1 in Sorghum bicolor to the
      Green Revolution Gene gibberellin20-oxidase Reveals a Positive Regulatory
      Association between Gibberellin and Cellulose Biosynthesis.
AB  - Here, we show a mechanism for expansion regulation through mutations in the green
      revolution gene gibberellin20 (GA20)-oxidase and show that GAs control
      biosynthesis of the plants main structural polymer cellulose. Within a 12,000
      mutagenized Sorghum bicolor plant population, we identified a single cellulose
      deficient and male gametophyte-dysfunctional mutant named dwarf1-1 (dwf1-1).
      Through the Sorghum propinquum male/dwf1-1 female F2 population, we mapped dwf1-1
      to a frameshift in GA20-oxidase. Assessment of GAs in dwf1-1 revealed ablation of
      GA. GA ablation was antagonistic to the expression of three specific cellulose
      synthase genes resulting in cellulose deficiency and growth dwarfism, which were
      complemented by exogenous bioactive gibberellic acid application. Using
      quantitative polymerase chain reaction, we found that GA was positively
      regulating the expression of a subset of specific cellulose synthase genes. To
      cross reference data from our mapped Sorghum sp. allele with another
      monocotyledonous plant, a series of rice (Oryza sativa) mutants involved in GA
      biosynthesis and signaling were isolated, and these too displayed cellulose
      deficit. Taken together, data support a model whereby suppressed expansion in
      green revolution GA genes involves regulation of cellulose biosynthesis. 

PMID- 26198261
TI  - Microplastic concentrations in beach sediments along the German Baltic coast.
AB  - The contamination with microplastic particles and fibres was evaluated on beaches
      along the German Baltic coast. Sediments were sampled near the Warnow and
      Oder/Peene estuaries, on Rugen island and along the Rostock coast to derive
      possible entry pathways. Seasonal variations were monitored along the Rostock
      coast from March to July 2014. After density separation in saline solution,
      floating particles were found to be dominated by sand grains. Water surface
      tension is shown to be sufficient to explain floatation of grains with sizes less
      than 1.5mm. Selecting intensely coloured particles and fibres, we find lower
      limits of the microplastic concentrations of 0-7 particles/kg and 2-11 fibres/kg
      dry sediment. The largest microplastic contaminations are measured at the Peene
      outlet into the Baltic Sea and in the North Sea Jade Bay. City discharges,
      industrial production sites, fishing activity and tourism are the most likely
      sources for the highest microplastic concentrations.

PMID- 26198262
TI  - Comparative immunohistochemical expression of beta-catenin, EGFR, ErbB2, and p63
      in adamantinomatous and papillary craniopharyngiomas.
AB  - Craniopharyngiomas (CPs) are rare epithelial tumors located mainly in the
      sellar/parasellar region. CPs have been classified into histopathologically,
      genetically, clinically and prognostically two distinctive subtypes:
      adamantinomatous and papillary variants. AIM: To determine the
      immunohistochemical expression of beta-catenin, EGFR, ErbB2, and p63 in
      adamantinomatous and papillary CPs. MATERIALS AND METHODS: beta-Catenin, EGFR,
      ErbB2, and p63 immunostaining was performed on paraffin embedded tissue sections
      of 25 CPs including 18 adamantinomatous craniopharyngioma (ACP) and 7 cases of
      papillary craniopharyngiomas (PCPs). RESULTS: 17 cases (94%) of ACP exhibited
      strong nuclear/cytoplasmic expression of beta-catenin. On the contrary, all cases
      of PCP showed exclusively membranous expression (P value<0.0001). Regarding EGFR,
      15 (83%) and 5 cases (71%) of APC and PCP respectively were positive. On the
      other hand, only 3 cases (17%) of APC and none of PCP exhibited positivity for
      ErbB2. p63 over-expression was observed in 16 cases of ACP (89%) and 6 cases of
      PCP (86%). However, the distribution of p63 staining was diffuse in ACP, while in
      PCP; the staining was mainly restricted to the basal cell layer. CONCLUSION:
      Nuclear accumulation of beta-catenin is a diagnostic hallmark of the ACP and is
      very helpful in the differential diagnosis between both ACP and PCP in the
      setting of small biopsies. Moreover, the restricted nuclear beta-catenin
      accumulation in the cohesive cell clusters within the whorl-like areas supports
      that aberrant beta-catenin expression may play a role in the morphogenesis of
      ACP.

PMID- 26198263
TI  - X Inactivation Lessons from Differentiating Mouse Embryonic Stem Cells.
AB  - X chromosome inactivation (XCI) is the dosage compensation mechanism that evolved
      in female mammals to correct the genetic imbalance of X-linked genes between
      sexes. X chromosome inactivation occurs in early development when one of the two
      X chromosomes of females is nearly-completely silenced. Differentiating Embryonic
      Stem cells (ESC) are regarded as a useful tool to study XCI, since they
      recapitulate many events occurring during early development. In this review we
      aim to summarise the advances in the field and to discuss the close connection
      between cell differentiation and X chromosome inactivation, with a particular
      focus on mouse ESCs. 

PMID- 26198264
TI  - Contrast leak mimicking detector malfunction in coronary artery calcium scoring.

PMID- 26198265
TI  - Assessment of the variability of vastii myoelectric activity in young healthy
      females during walking: a statistical gait analysis.
AB  - The study was designed to assess the natural variability of the activation
      modalities of vastus medialis (VM) and vastus lateralis (VL) during walking at a
      self-selected speed and cadence of 30 young, healthy, females. This was achieved
      by conducting statistical gait analysis on the surface electromyographic signals
      from hundreds of strides for each subject. Results revealed variability in the
      number of activations, occurrence frequency, and onset-offset instants across the
      thousands of strides analyzed. However, despite the variability, there was one
      activation occurrence which remained consistent across subjects for both VM and
      VL. This occurred from terminal swing to the following loading response (observed
      in 100% of strides). A second, less frequent, activation occurred between mid
      stance up to pre-swing (observed in 39.3+/-22.4% of strides for VM and in 35.1+/
      20.6% for VL). No significant differences (p>0.05) were observed in the onset
      offset instants or in the occurrence frequency, which suggest a simultaneous
      recruitment of VM and VL. This "normality" pattern represents the first attempt
      at developing a reference frame for vastii sEMG activity during walking, that is
      able to include the physiological variability of the phenomenon and control the
      confounding effects of age and gender. 

PMID- 26198266
TI  - Identification of a unique atrioventricular accessory pathway related to the
      small cardiac vein with right atrial orifice.

PMID- 26198267
TI  - MTA3 regulates differentiation of human cytotrophoblast stem cells.
AB  - INTRODUCTION: Early placental development depends on the correct balance of
      cytotrophoblast (CTB) proliferation and differentiation, into either
      syncytiotrophoblast (STB) involved in nutrient/gas exchange, or invasive
      extravillous trophoblast (EVT) involved in establishment of blood flow to the
      placenta. Metastasis associated protein-3 (MTA3) is a transcriptional co
      repressor known to regulate cell migration. In addition, MTA3 is reportedly
      decreased in preeclampsia. We set out to investigate the role of MTA3 in human
      trophoblast differentiation. METHODS: We co-stained first and third trimester
      placental sections with antibodies to MTA3 and other trophoblast markers. We also
      evaluated MTA3 expression following in vitro differentiation of primary isolated
      CTB. In order to evaluate the role of MTA3 in trophoblast differentiation, we
      used lentiviral constructs to overexpress and knock down its expression.
      Trophoblast differentiation was assessed by a combination of marker expression
      and functional assays, including hCG ELISA and cell migration. RESULTS: MTA3 was
      abundantly expressed in CTB and proximal cell column EVT in the human placenta
      and decreased with further differentiation into STB and mature EVT. MTA3
      knockdown in JEG3 resulted in a 2-3 fold decrease in STB markers, CGB and GCM1,
      as well as in hCG secretion. In terms of EVT differentiation, MTA3 knockdown led
      to a 1.5-2 fold increase in HLA-G and cell migration, but decreased the mature
      EVT marker ITGA1. DISCUSSION: Taken together, our data suggest a role for MTA3 in
      terminal trophoblast differentiation into both hCG-secreting STB and mature EVT.

PMID- 26198269
TI  - Investigation into the metallophilic interaction in coinage-metal halides: an ab
      initio study of CMX (CM = Cu and Ag, X = F - I).
AB  - Investigation of the metallophilic interactions of the title coinage-metal halide
      series, CMX (CM = Ag and Cu, X = F - I), and their cationic and anionic systems,
      were performed at CCSD(T) theoretical level with extended basis sets. Natural
      bond orbital analysis shows that the interactions come mainly from the overlap of
      the sp hybrid on the halogen and the spd hybrid on the coinage-metal atom.
      Electron density deformation analysis demonstrates a pronounced electron
      accumulation in the interaction region between the heavier X and the coinage
      metal atoms, and suggests a covalent character of the interaction. Positive
      Laplacian values and negative total energy densities at bond critical points
      (BCPs) show the "intermediate" character of the interactions. Reduced density
      gradient analysis visualizes the interaction; a linear relationship between
      energy densities and eigenvalues can be found at BCPs.

PMID- 26198270
TI  - Theoretical studies of nickel-catalyzed ring-opening hydroacylation of
      methylenecyclopropanes and benzaldehydes.
AB  - Density functional theory (DFT) was used to investigate nickel-catalyzed ring
      opening hydroacylation of methylenecyclopropanes and benzaldehydes. The results
      indicated that the Ni-P(n-Bu)3 complex exhibited much more excellent catalysis
      than the other two complexes (Ni-PMe3 and Ni-P(t-Bu)3). The hydrogen migration
      was the rate-determining step, and the beta-carbon elimination was the chirality
      limiting step. The dominant product was a (S,S)- cis ketone. The phosphine ligand
      P(n-Bu)3 changed the rate-determining step, and greatly decreased the free
      energies of the rate-determining step and chirality-limiting step. The use of P(n
      Bu)3 generally decreased the free energies of the intermediates and transition
      states. The possible role of P(n-Bu)3 was the transformation of the electron and
      geometry structures of those intermediates and transition states. Graphical
      Abstract DFT results indicated that the Ni-P(n-Bu)3 complex exhibited much more
      excellent catalysis than the other two complexes (Ni-PMe3 and Ni-P(t-Bu)3). The
      phosphine ligand P(n-Bu)3 changed the rate-determining step, and greatly
      decreased the free energies of the rate-determining step and chirality-limiting
      step. 

PMID- 26198271
TI  - G3(MP2)-CEP theory and applications for compounds containing atoms from
      representative first, second and third row elements of the periodic table.
AB  - The compact effective potential (CEP) pseudopotential was adapted to the G3(MP2)
      theory, herein referred to as G3(MP2)-CEP, and applied to the calculation of
      enthalpies of formation, ionization energies, atomization energies, and electron
      and proton affinities for 446 species containing elements of the 1st, 2nd, and
      3rd rows of the periodic table. A total mean absolute deviation of 1.67 kcal mol(
      1) was achieved with G3(MP2)-CEP, compared with 1.47 kcal mol(-1) for G3(MP2).
      Electron affinities and enthalpies of formation are the properties exhibiting the
      lowest deviations with respect to the original G3(MP2) theory. The use of
      pseudopotentials and composite theories in the framework of the G3 theory is
      feasible and compatible with the all electron approach. Graphical Abstract
      Application of composite methods in high-level ab initio calculations.

PMID- 26198272
TI  - Oncologists' End of Life Treatment Decisions.
AB  - BACKGROUND: Optimal treatment decisions for older end-stage cancer patients are
      complicated, and are influenced by oncologists' attitudes and beliefs about older
      patients. Nevertheless, few studies have explored oncologists' perspectives on
      how patient age affects their treatment decisions. METHODS: In-depth interviews
      were conducted with 17 oncologists to examine factors that influence their
      chemotherapy decisions for adults with incurable cancer near death. Transcripts
      of recorded interviews were coded and content analyzed. RESULTS: Oncologists
      identified patient age as a key factor in their chemotherapy decisions. They
      believed older adults were less likely to want or tolerate treatment, and felt
      highly motivated to treat younger patients. DISCUSSION: Qualitative analysis of
      in-depth interviews resulted in a nuanced understanding of how patient age
      influences oncologists' chemotherapy decisions. Such understanding may inform
      practice efforts aimed at enhancing cancer care at the end of life for older
      patients.

PMID- 26198273
TI  - Sitagliptin Results in a Decrease of Truncated Apolipoprotein C1.
AB  - Apolipoprotein C1 (ApoC1) is a component of multiple lipoproteins where it
      performs a variety of roles in lipid metabolism and transport. ApoC1 exists as
      both full-length and truncated isoforms. Truncation of ApoC1 has been postulated
      to result from the action of dipeptidyl peptidase-4 (DPP-4), the target of a new
      class of diabetes drugs that includes sitagliptin phosphate. In this study, we
      sought to determine if oral administration of sitagliptin altered the proportion
      of ApoC1 isoforms circulating in humans. Results indicated a dramatic change in
      ApoC1 truncation, consistent with a high level of DPP-4 inhibition by
      sitagliptin. FUNDING: University of Minnesota, Minneapolis, MN, USA.

PMID- 26198274
TI  - Web of industry, advocacy, and academia in the management of osteoporosis.

PMID- 26198276
TI  - Acute pulmonary embolism caused by highly aggregated intravenous immunoglobulin.
AB  - BACKGROUND AND OBJECTIVES: Six patients died and one patient survived following
      infusion of a specific lot of intravenous immunoglobulin (IVIG) within half an
      hour in May 2008. This study elucidated the underlying pathogenesis. MATERIALS
      AND METHODS: A variety of protein fractionation and identification approaches
      were employed to determine the abnormal components in IVIG products obtained from
      the hospital where the patients were treated. Animal studies using mice and
      monkeys were conducted to elucidate the pathophysiological mechanisms. In animal
      experiments, the effect and distribution of immunoglobulin was investigated using
      HE staining and immunohistochemistry (IHC) separately, while platelets and
      fibrinogen depletion were utilized to determine a possible link between
      thromboembolism formation in animals and the lethal effect of the IVIG. The size
      and distribution of the protein aggregates were determined with Coulter Counter
      Multisizer-3 after the dilution of the IVIG with plasma, and the lethal effect of
      the protein aggregates was simulated with artificial microparticles. RESULTS: The
      IVIG retrieved from the hospital was found to have striking similarities to the
      heat-treated IVIG in terms of protein aggregation profiles and lethal effects.
      Post-mortem examination indicated that immunoglobulin aggregates were mainly
      found in the lung of the animals, while depletion of platelets and fibrinogen
      from the IVIG preparations failed to prevent the death of the animals. Similar
      amount of artificial microparticles caused animal death in similar fashion.
      CONCLUSIONS: Our findings indicate that the retrieved IVIG exerted its lethal
      effects by blocking the pulmonary circulation without markedly altering the
      coagulation cascade or immunological events.

PMID- 26198275
TI  - Long-term growth hormone treatment in short children with CKD does not accelerate
      decline of renal function: results from the KIGS registry and ESCAPE trial.
AB  - BACKGROUND: Recombinant human (rh) growth hormone (GH) raises the glomerular
      filtration rate (GFR) in healthy individuals. Concern has been raised that long
      term rhGH treatment in short children with chronic kidney disease (CKD) may
      accelerate the progression of CKD via induction of glomerular hyperfiltration.
      PATIENTS AND METHODS: We compared the decline in GFR in children with CKD
      enrolled in two large clinical studies with (KIGS registry) and without (ESCAPE
      trial) concomitant rhGH treatment and followed for up to 10 years. Estimated GFR
      (eGFR) was determined at yearly intervals. The annual decline in eGFR was
      analyzed cross-sectionally for up to 10 years and longitudinally for 5 years.
      RESULTS: In the KIGS registry 367 patients with CKD stages II-IV (mean age 8.0
      years; 72% boys; mean eGFR 38.4 ml/min/1.73 m(2)) were treated with 0.33 mg
      rhGH/kg per week for at least 1 year. In the ESCAPE trial 274 non-rhGH-treated
      patients with CKD stages II-IV (mean age 11.6 years; 61% boys; mean GFR 47.3
      ml/min/1.73 m(2)) were followed for at least 1 year. At the 5-year follow-up, the
      mean loss of eGFR in the KIGS children receiving continuous rhGH treatment (n =
      97) did not differ significantly from that in the controls (n = 113) in the
      ESCAPE trial (-5.8 vs. -8.6 ml/5 years, respectively; p = 0.17). Absolute height
      and eGFR at baseline were significant correlates of the annual eGFR loss (model R
      (2) =0.121). CONCLUSIONS: Long-term rhGH-treatment does not accelerate the
      decline in GFR in short children with CKD. Height and baseline eGFR are
      significant predictors of the loss of GFR in CKD patients.

PMID- 26198278
TI  - Atypical presentation of moyamoya disease in an infant with a de novo RNF213
      variant.
AB  - Variants in RNF213 lead to susceptibility to moyamoya disease, a rare cerebral
      angiopathy characterized by bilateral stenosis of the internal carotid arteries
      and development of a compensatory collateral network. We describe a 3-month-old
      female with seizures, arterial narrowing involving the internal carotid and
      intracranial arteries and inferior abdominal aorta, and persistently elevated
      transaminases. Whole exome sequencing demonstrated a novel de novo variant in
      RNF213, securing a molecular diagnosis and directing appropriate intervention.
      This report underscores the role of whole exome sequencing in cases for which a
      complex and atypical presentation may mask diagnosis. Furthermore, the early and
      severe presentation in our patient, in conjunction with a novel de novo RNF213
      variant, suggests that specific variants in RNF213 may lead to a Mendelian form
      of disease rather than simply conferring susceptibility to multifactorial
      disease.

PMID- 26198279
TI  - Trabeculectomy for normal tension glaucoma: outcomes using the Moorfields Safer
      Surgery technique.
AB  - AIMS: To evaluate long-term outcomes and complications of trabeculectomy for
      normal tension glaucoma (NTG) with contemporary surgical techniques. METHODS:
      Retrospective consecutive, non-comparative case series of 131 eyes of 98 patients
      undergoing trabeculectomy between 2007 and 2013 in a dedicated NTG clinic. Data
      collected during routine clinical care were analysed. Assessment of clinical
      outcomes included intraocular pressure (IOP) reduction, bleb function, final
      visual acuity, evidence of glaucoma progression, postoperative complications and
      further surgical intervention. Surgical failure was defined as a failure to meet
      specified IOP-related criteria, the need to undergo further glaucoma surgery for
      raised IOP or loss of light perception vision. A further analysis was also
      performed which considered failure as glaucoma progression following surgery.
      Outcomes were evaluated using Kaplan-Meier life-table analysis. RESULTS: The
      cumulative percentages of unqualified success as defined by a >=30% reduction of
      IOP from baseline preoperative maximum (95% CI; IOP of all eyes: mean+/-SD) at 1,
      2, 3 and 4 years after surgery were 91.1% (84.1% to 95.1%; 9.7+/-2.9 mm Hg),
      74.1% (63.7% to 81.8%; 10.3+/-3.0 mm Hg), 64.8% (52.7% to 74.6%; 10.6+/-2.5 mm
      Hg) and 62.1% (49.3% to 72.6%; 10.2+/-2.1 mm Hg), respectively. At 2 years of
      follow-up there was no significant association between either previous cataract
      surgery or ethnicity and failure. Cumulative percentages of unqualified success
      at 4 years after surgery as defined by a filtering trabeculectomy bleb or absence
      of glaucoma progression were 91.6% (83.2% to 95.9%) and 92.3% (81.3% to 97.0%),
      respectively. Postoperative complications such as early (2.3%) and late (0.8%)
      hypotony were significantly lower than suggested by the current literature.
      CONCLUSIONS: Trabeculectomy in NTG patients undertaken using contemporary
      surgical techniques and intensive postoperative management is associated with
      more successful long-term outcomes and fewer complications than the currently
      available literature suggests.

PMID- 26198280
TI  - Vitrectomy with or without encircling band for pseudophakic retinal detachment: a
      multi-centre, three-arm, randomised clinical trial. VIPER Study Report No. 1-
      design and enrolment.
AB  - PURPOSE: Scleral buckling is currently used in addition to vitrectomy for the
      treatment of pseudophakic retinal detachment (PRD) to better support the vitreous
      base and better visualisation of the periphery. AIMS: The aims of this study are
      to evaluate (1) whether the combination of 20 G vitrectomy and scleral buckling
      is superior to 20 G vitrectomy alone (control) (confirmatory), and (2) whether
      transconjunctival 23/25 G vitrectomy is non-inferior to 20 G vitrectomy (both
      without scleral buckling) regarding operation success (exploratory). METHODS: The
      VIPER (Vitrectomy Plus Encircling Band Vs. Vitrectomy Alone For The Treatment Of
      Pseudophakic Retinal Detachment) study is an unmasked, multi-centre, three-arm
      randomised trial. Patients with PRD were eligible, excluding complicated retinal
      detachment or otherwise severe ophthalmologic impairment. Patients were
      randomised to one of three interventions: 20 G vitrectomy alone (control C),
      combination of 20 G vitrectomy and circumferential scleral buckling (experimental
      treatment E1) or 23/25 G vitrectomy alone (experimental treatment E2). The
      primary endpoint is the absence of any indication for a retina re-attaching
      procedure during 6 months of follow-up. Secondary endpoints include best
      corrected visual acuity, retina re-attaching procedures, complications and
      adverse events. RESULTS: From June 2011 to August 2013, 257 patients were
      enrolled in the study. The internet randomisation service assigned 100 patients
      each to the treatment arms C and E1, and 57 patients to treatment E2. The
      imbalance is due to the fact that several retinal surgeons did not qualify for
      performing E2. The random assignment was stratified and balanced (ie, 1:1 or
      1:1:1 ratio) by surgeon. CONCLUSIONS: The described study represents a
      methodologically rigorous protocol evaluating the benefits of three different
      vitrectomy approaches to PRD. The projected results will help to establish their
      overall efficacy and will permit conclusions regarding their relative value.
      TRIAL REGISTRATION NUMBER: DRKS00003158 (German Clinical Trials Register, DRKS).

PMID- 26198281
TI  - What do patients with strabismus expect post surgery? The development and
      validation of a questionnaire.
AB  - AIMS: To develop and validate a short questionnaire to assess patients'
      expectations about outcomes post strabismus surgery. METHODS: Questionnaire items
      were extracted from previous literature and reviewed by a multidisciplinary team.
      A cross-sectional study was then undertaken with 220 adult patients due to
      undergo strabismus surgery. Participants completed the 17-item questionnaire.
      Scale structure was explored using principal component analysis (PCA), and the
      subscales analysed in relation to demographic and clinical characteristics and
      psychosocial well-being in order to establish validity. RESULTS: PCA revealed a 3
      factor solution for the Expectations of Strabismus Surgery Questionnaire (ESSQ):
      (a) intimacy and appearance-related issues, (b) visual functioning, (c) social
      relationships. This 3-factor solution explained 59.30% of the overall variance in
      the ESSQ. Internal consistency, content and nomological and concurrent validity
      were considered acceptable. CONCLUSIONS: Patients with strabismus have high
      expectations about their postsurgical outcomes. This questionnaire provides a
      useful tool to assess the expectations patients have about their surgery, whether
      these expectations change over time and how they impact on postsurgical outcomes.

PMID- 26198282
TI  - Density Functional Theory Study of Atomic Layer Deposition of Zinc Oxide on
      Graphene.
AB  - The dissociation of zinc ions (Zn(2+)) from vapor-phase zinc acetylacetonate,
      Zn(C5H7O2)2, or Zn(acac)2 and its adsorption onto graphene oxide via atomic layer
      deposition (ALD) were studied using a quantum mechanics approach. Density
      functional theory (DFT) was used to obtain an approximate solution to the
      Schrodinger equation. The graphene oxide cluster model was used to represent the
      surface of the graphene film after pre-oxidation. In this study, the geometries
      of reactants, transition states, and products were optimized using the B3LYB/6
      31G** level of theory or higher. Furthermore, the relative energies of the
      various intermediates and products in the gas-phase radical mechanism were
      calculated at the B3LYP/6-311++G** and MP2/6-311 + G(2df,2p) levels of theory.
      Additionally, a molecular orbital (MO) analysis was performed for the products of
      the decomposition of the Zn(acac)2 complex to investigate the dissociation of
      Zn(2+) and the subsequent adsorption of H atoms on the C5H7O2 cluster to form
      acetylacetonate enol. The reaction energies were calculated, and the reaction
      mechanism was accordingly proposed. A simulation of infrared (IR) properties was
      performed using the same approach to support the proposed mechanism via a
      complete explanation of bond forming and breaking during each reaction step. 

PMID- 26198283
TI  - Effects of different bronchoalveolar lavage methods on tracheobronchial foreign
      body patients.
AB  - OBJECTIVES/HYPOTHESIS: To compare the different effects of bronchoalveolar lavage
      (BAL) with diverse combinations of lidocaine, epinephrine, and dexamethasone on
      pediatric patients with an inhaled tracheobronchial foreign body (TFB). STUDY
      DESIGN: Randomized controlled study. METHODS: Two hundred forty cases of
      pediatric patients with inhaled TFB were included in this study, and were
      randomly divided into four groups using three kinds of drugs for BAL, namely 0.9%
      saline (S) group, 2% lidocaine with diluted epinephrine (LE) group, 2% lidocaine
      with diluted epinephrine and 0.5% dexamethasone (LED), control group (C) without
      BAL. The incidences of intraoperative or postoperative complications and recovery
      periods were compared. Meanwhile, the concentrations of interleukin (IL)-1beta,
      IL-6, and tumor necrosis factor (TNF)-alpha in BAL fluids and plasma were
      evaluated by enzyme-linked immunosorbent assay. RESULTS: The incidences of
      bronchospasm, hypoxemia, and postoperative fever were significantly lower in the
      LED group than other groups (P < .001). Fever after the TFB removal procedure
      appeared later in the LED group than the other groups. The improvement and
      healing periods in the LE and LED groups were significantly shorter than those in
      the C and S groups (P < .001). The concentrations of IL-1beta, IL-6, and TNF
      alpha in BAL fluids were significantly higher in the LE and LED groups than those
      in the S group (P < .001), but those in the plasma of the C and S groups were
      lower compared with the LE and LED groups (P < .001). CONCLUSIONS: BAL with
      lidocaine, epinephrine, and dexamethasone could promote recovery for TFB patients
      and reduce incidences of complications, possibly by regulating release of
      proinflammatory cytokines. LEVEL OF EVIDENCE: 1b.

PMID- 26198284
TI  - Four-phase rhinomanometry: a multicentric retrospective analysis of 36,563
      clinical measurements.
AB  - Rhinomanometry can still be considered as the standard technique for the
      objective assessment of the ventilatory function of the nose. Reliable technical
      requirements are given by fast digital sensors and modern information technology.
      However, the xyimaging of the pressure-flow relation typically shows loops as a
      sign of hysteresis, with the need for resolution of the breath in four phases.
      The three pillars of 4-phase rhinomanometry (4PR) are the replacement of
      estimations by measurements, the introduction of parameters related to the
      subjective sensing of obstruction, and the graphical information regarding the
      disturbed function of the nasal valve. In a meta-analysis of 36,563 clinical
      measurements, we analyze the errors of the "classic" parameters (flow in 150 Pa)
      and reject the further use of these parameters as obsolete, because they
      correspond to an inaccurate estimation rather than proper measurement. In a pre
      study of 1580 measurements, the logarithmic effective resistance (Reff) was found
      to have the highest correlation with values obtained from a visual analog scale.
      Next, we classify the inspiratory effective resistance in 20,069 measurements
      without treatment and 16,494 measurements after decongestion with xylometazoline
      0.1 % spray in 20 % percentiles. The gradation of obstruction delivers not only
      "normal" values but also indications for the severity of the obstruction in adult
      Caucasian noses. Adoption of the distribution for the growing nose and analysis
      of the total nasal resistance is addressed, and typical findings of nasal valve
      phenomena are outlined.

PMID- 26198285
TI  - Prognostic factors of locally invasive well-differentiated thyroid carcinoma
      involving the trachea.
AB  - To report our experience with tracheal invasive thyroid carcinoma with emphasis
      on clinical characteristics and treatment modalities, and to identify the
      prognostic factors for tracheal invasive thyroid carcinoma. Totally 1919 patients
      underwent surgical extirpation of thyroid cancer from 1990 to 2010. Among them,
      65 patients had well-differentiated thyroid cancer with tracheal invasion. The
      incidence was higher in male and older patients. Patients were treated with
      tracheal shave excision (n = 18), tracheal resection (n = 37) and total
      laryngectomy (n = 10). Locoregional recurrence occurred in 39 patients, and
      metastasis occurred in 25 patients. Simultaneous involvement of the trachea and
      the esophagus was associated with locoregional recurrence (p = 0.039) in
      univariate analysis, but not confirmed by multivariate analysis. There was
      significant difference in the disease-specific survival (DSS) according to
      laryngeal involvement (p = 0.002). All the patient in the shave excision group
      survived until the end of the study period. Although it is categorized in same
      classification of T4a, simultaneous involvement of the trachea and the esophagus
      showed higher locoregional recurrence and laryngeal involvement showed lower DSS.
      Despite the invasion of thyroid cancer into the adjacent aerodigestive tract,
      many patients showed long survival when they underwent appropriate surgery. 

PMID- 26198287
TI  - A Novel Scheme of Thermographic Microimaging Using Pyro-Magneto-Optical Indicator
      Films.
AB  - A new method of imaging of temperature distributions is presented. The method is
      based on the use of a BiLu2 Fe4 GaO12 ferrimagnetic garnet layer as a pyro
      magneto-optical detection layer. Thermal imaging with high sensitivity, with
      micrometer spatial and with millisecond temporal resolution is demonstrated in a
      contactless read-out scheme. 

PMID- 26198286
TI  - Impact of Contrast-Induced Acute Kidney Injury After Percutaneous Coronary
      Intervention on Short- and Long-Term Outcomes: Pooled Analysis From the HORIZONS
      AMI and ACUITY Trials.
AB  - BACKGROUND: Contrast-induced acute kidney injury (CI-AKI), defined as a serum
      creatinine increase >=0.5 mg/dL or >=25% within 72 hours after contrast exposure,
      is a common complication of procedures requiring contrast media and is associated
      with increased short- and long-term morbidity and mortality. Few studies describe
      the effects of CI-AKI in a large-scale acute coronary syndrome population, and
      the relationship between CI-AKI and bleeding events has not been extensively
      explored. We sought to evaluate the impact of CI-AKI after percutaneous coronary
      intervention in patients presenting with acute coronary syndrome. METHODS AND
      RESULTS: We pooled patient-level data for 9512 patients from the percutaneous
      coronary intervention cohorts of the Harmonizing Outcomes With Revascularization
      and Stents in Acute Myocardial Infarction (HORIZONS-AMI) and Acute
      Catheterization and Urgent Intervention Triage Strategy (ACUITY) multicenter
      randomized trials. Patients were classified according to CI-AKI development, and
      cardiovascular outcomes at 30 days and 1 year were compared between groups. A
      total of 1212 patients (12.7%) developed CI-AKI. Patients with CI-AKI were older,
      with a more extensive comorbidity profile than without CI-AKI. Multivariable
      analysis confirmed several previously identified predictors of CI-AKI, including
      diabetes mellitus, contrast volume, age, and baseline hemoglobin. Mortality rates
      were significantly higher in the CI-AKI group at 30 days (4.9% versus 0.7%;
      P<0.0001) and 1 year (9.8% versus 2.9%; P<0.0001), as were rates of 1-year
      myocardial infarction, definite/probable stent thrombosis, target lesion
      revascularization, and major adverse cardiac events. Major bleeding (13.8% versus
      5.4%; hazard ratio, 2.64; 95% confidence interval, 2.21-3.15; P<0.0001) was also
      higher in patients with CI-AKI. After multivariable adjustment, results were
      unchanged. CONCLUSIONS: CI-AKI after percutaneous coronary intervention in
      patients presenting with acute coronary syndrome is independently associated with
      increased risk of short- and long-term ischemic and hemorrhagic events. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers:
      NCT00433966 (HORIZONS-AMI) and ACUITY (NCT00093158).

PMID- 26198288
TI  - The effect of raw materials on thermo-oxidative stability and glycidyl ester
      content of palm oil during frying.
AB  - BACKGROUND: The objective of this research was to determine the effects of the
      water content of food incorporated into frying oil on oil degradation and the
      content of glycidyl esters. Potato chips, French fries and snacks were fried
      intermittently in palm oil, which was heated at 180  degrees C for 8 h per day
      over five consecutive days. Thermo-oxidative and physical alterations, changes in
      fatty acid composition, total polar components, polar fraction composition, and
      water content were analysed. The content of glycidyl esters was measured by
      liquid chromatography-tandem mass spectrometry. RESULTS: More polar compounds
      were formed in the oil used for frying chips (252 g kg(-1)) than for French fries
      (229 g kg(-1)) or snacks (196 g kg(-1)). Reductions in glycidyl esters were found
      in oils used for frying--greater for frying snacks and French fries (95% and 93%)
      than for potato chips (87%). The rate of decrease of glycidyl esters was
      correlated with frying parameters, most strongly with the concentrations of
      diacylglycerols (r = 0.98) and total polar components (r = -0.98). CONCLUSION:
      The raw material had a greater influence on polymerization conversion and
      glycidyl ester content than on hydrolytic and oxidative changes in the frying
      oil.

PMID- 26198289
TI  - Angiographic appearance of spontaneous coronary artery dissection with intramural
      hematoma proven on intracoronary imaging.
AB  - BACKGROUND: The pathognomonic appearance of multiple radiolucent lumen on
      angiography is used to diagnose spontaneous coronary artery dissection (SCAD).
      However, this finding is absent in >70% of SCAD, in which case optical coherence
      tomography (OCT) or intravascular ultrasound (IVUS) is useful to assess arterial
      wall integrity. METHODS: We report the angiographic appearance of SCAD that were
      proven on intracoronary imaging with OCT or IVUS. Our angiographic classification
      and algorithm for SCAD diagnosis was previously reported. Patients with type 1
      SCAD (multiple radiolucent lumen) do not require OCT/IVUS, whereas, it was
      recommended for those with suspected type 2 (diffuse stenosis) or 3 (mimic
      atherosclerosis) SCAD. RESULTS: Twenty-two consecutive patients with non-type 1
      angiographic SCAD in 25 coronary arteries (22 OCT and 4 IVUS) were studied. Mean
      age was 52.9 +/- 9.9 years, 89.5% were women, and 16/22 (72.7%) had underlying
      fibromuscular dysplasia. Sixteen SCAD arteries were type 2 SCAD, and nine were
      type 3. All 25 SCAD arteries had intramural hematoma and intimomedial membrane
      separation with double lumen on OCT or IVUS. The mean visual angiographic
      stenosis was 74.6 +/- 17.5% (range 40-100%). Dissected segments were long with
      mean qualitative coronary analysis (QCA) length 45.2 +/- 29.2 mm, especially in
      patients with type 2 SCAD (mean QCA length 58.3 +/- 29.0 mm). The mean QCA length
      in type 3 SCAD lesions was 22.1 +/- 5.7 mm. CONCLUSIONS: Intracoronary imaging
      confirms that SCAD may appear angiographically without multiple radiolucent
      lumen. Angiographers should be familiar with angiographic SCAD variants to
      improve SCAD diagnosis, and utilize intracoronary imaging when the diagnosis is
      uncertain.

PMID- 26198290
TI  - Investigation of the composition of anabolic tablets using near infrared
      spectroscopy and Raman chemical imaging.
AB  - The use of performance enhancing drugs is a widespread phenomenon in professional
      and leisure sports. A spectroscopic study was carried out on anabolic tablets
      labelled as 5 mg methandienone tablets provided by police departments. The
      analytical approach was based on a two-step methodology: a fast analysis of
      tablets using near infrared (NIR) spectroscopy to assess sample homogeneity based
      on their global composition, followed by Raman chemical imaging of one sample per
      NIR profile to obtain information on sample formulation. NIR spectroscopy
      assisted by a principal components analysis (PCA) enabled fast discrimination of
      different profiles based on the excipient formulation. Raman hyperspectral
      imaging and multivariate curve resolution - alternating least square (MCR-ALS)
      provided chemical images of the distribution of the active substance and
      excipients within tablets and facilitated identification of the active compounds.
      The combination of NIR spectroscopy and Raman chemical imaging highlighted dose
      to-dose variations and succeeded in the discrimination of four different
      formulations out of eight similar samples of anabolic tablets. Some samples
      contained either methandienone or methyltestosterone whereas one sample did not
      contain an active substance. Other ingredients were sucrose, lactose, starch or
      talc. Both techniques were fast and non-destructive and therefore can be carried
      out as exploratory methods prior to destructive screening methods. Copyright (c)
      2015 John Wiley & Sons, Ltd. 

PMID- 26198291
TI  - Metallothionein 2 regulates endothelial cell migration through transcriptional
      regulation of vegfc expression.
AB  - Analysis of developmental angiogenesis can help to identify regulatory networks,
      which also contribute to disease-related vascular growth. Vascular endothelial
      growth factors (Vegf) drive angiogenic processes such as sprouting, endothelial
      cell (EC) migration and proliferation. However, how Vegf expression is regulated
      during development is not well understood. By analyzing developmental zebrafish
      angiogenesis, we have identified Metallothionein 2 (Mt2) as a novel regulator of
      vegfc expression. While Metallothioneins (Mts) have been extensively analyzed for
      their capability of regulating homeostasis and metal detoxification, we
      demonstrate that Mt2 is required for EC migration, proliferation and angiogenic
      sprouting upstream of vegfc expression. We further demonstrate that another Mt
      family member cannot compensate Mt2 deficiency and therefore postulate that Mt2
      regulates angiogenesis independent of its canonical Mt function. Our data not
      only reveal a non-canonical function of Mt2 in angiogenesis, but also propose Mt2
      as a novel regulator of vegfc expression. 

PMID- 26198293
TI  - Constitutional genetic association with CALR mutations?

PMID- 26198294
TI  - Fluctuation of potential zinc status biomarkers throughout a reproductive cycle
      of primiparous and multiparous sows.
AB  - Fluctuations in Zn metabolism throughout gestation and lactation might affect Zn
      requirements. However, scientific data on Zn requirements for breeding sows are
      limited. The objective of the present study was to assess the Zn status of
      primiparous and multiparous sows using different Zn status biomarkers, to
      identify periods of critical Zn status throughout the reproductive cycle at
      different parities. Blood samples were taken after overnight fasting before
      feeding in the morning from five primiparous and ten multiparous sows at fixed
      time intervals during gestation (days - 5, 0 (insemination), 21, 42, 63 and 84),
      around parturition (days 108, 112, 115 (parturition) and 118) and during
      lactation (days 122, 129 and 143 (weaning)). At parturition, blood samples were
      collected from two randomly selected piglets per sow before colostrum intake.
      Plasma was analysed for Zn and Cu contents, whereas serum was analysed for
      alkaline phosphatase, metallothionein and albumin concentrations. Independently
      of parity, all biomarkers fluctuated differently during gestation and lactation
      (P< 0.050). This reflects their different roles in Zn metabolism, and suggests
      that the choice of a Zn status biomarker necessitates careful consideration. Low
      average plasma Zn concentration at the end of gestation and throughout lactation
      seem to be replenished towards weaning.

PMID- 26198292
TI  - The pathogenic role of angiogenesis in rheumatoid arthritis.
AB  - Angiogenesis is the formation of new capillaries from pre-existing vasculature,
      which plays a critical role in the pathogenesis of several inflammatory
      autoimmune diseases such as rheumatoid arthritis (RA), spondyloarthropathies,
      psoriasis, systemic lupus erythematosus, systemic sclerosis, and atherosclerosis.
      In RA, excessive migration of circulating leukocytes into the inflamed joint
      necessitates formation of new blood vessels to provide nutrients and oxygen to
      the hypertrophic joint. The dominance of the pro-angiogenic factors over the
      endogenous angiostatic mediators triggers angiogenesis. In this review article,
      we highlight the underlying mechanisms by which cells present in the RA synovial
      tissue are modulated to secrete pro-angiogenic factors. We focus on the
      significance of pro-angiogenic factors such as growth factors, hypoxia-inducible
      factors, cytokines, chemokines, matrix metalloproteinases, and adhesion molecules
      on RA pathogenesis. As pro-angiogenic factors are primarily produced from RA
      synovial tissue macrophages and fibroblasts, we emphasize the key role of RA
      synovial tissue lining layer in maintaining synovitis through neovascularization.
      Lastly, we summarize the specific approaches utilized to target angiogenesis. We
      conclude that the formation of new blood vessels plays an indispensable role in
      RA progression. However, since the function of several pro-angiogenic mediators
      is cross regulated, discovering novel approaches to target multiple cascades or
      selecting an upstream cascade that impairs the activity of a number of pro
      angiogenic factors may provide a promising strategy for RA therapy. 

PMID- 26198295
TI  - Systematic review with meta-analysis: coffee consumption and the risk of
      gallstone disease.
AB  - BACKGROUND: Epidemiologic evidence on coffee consumption reducing the risk of
      gallstone disease has been contradictory. AIM: To perform a meta-analysis of
      observational studies, to investigate an association and dose-response of coffee
      consumption with gallstone disease. METHODS: We used PubMed and EMBASE databases
      to identify all published studies before June 2015. A random-effects model was
      used to compute a pooled relative risk (RR) and corresponding 95% confidence
      intervals (CIs). RESULTS: One case-control study and five prospective cohort
      studies (with seven cohorts) involving 227,749 participants and 11,477 gallstone
      disease cases were included. Coffee consumption was significantly associated with
      a reduced risk of gallstone disease (RR, 0.83; 95% CI, 0.76 to 0.89; I(2) =
      35.9%), based on prospective studies; specifically, we observed an inverse
      relation in females, but not in males. The case-control study did not reveal any
      association between coffee and gallstone disease (OR, 0.99; 95% CI, 0.64 to
      1.53). In a dose-response analysis, the RR of gallstone disease was 0.95 (95% CI,
      0.91 to 1.00; P = 0.049) per 1 cup/day of coffee consumption. A significant
      nonlinear dose-response association was also identified (P for nonlinearity =
      0.0106). For people who drank 2, 4 and 6 cups of coffee per day, the estimated
      RRs of gallstone disease were 0.89 (95% CI, 0.79 to 0.99), 0.81 (95% CI, 0.72 to
      0.92) and 0.75 (95% CI, 0.64 to 0.88), respectively, compared with the lowest
      level drinkers. CONCLUSION: This study suggests that coffee consumption is
      related to a significantly decreased risk of gallstone disease.

PMID- 26198296
TI  - Transcriptomic differences between day and night in Acropora millepora provide
      new insights into metabolite exchange and light-enhanced calcification in corals.
AB  - The evolutionary success of reef-building corals is often attributed to their
      symbiotic relationship with photosynthetic dinoflagellates of the genus
      Symbiodinium, but metabolic interactions between the partners and the molecular
      bases of light-enhanced calcification (LEC) are not well understood. Here, the
      metabolic bases of the interaction between the coral Acropora millepora and its
      dinoflagellate symbiont were investigated by comparing gene expression levels
      under light and dark conditions at the whole transcriptome level. Among the 497
      differentially expressed genes identified, a suite of genes involved in
      cholesterol transport was found to be upregulated under light conditions,
      confirming the significance of this compound in the coral symbiosis. Although ion
      transporters likely to have roles in calcification were not differentially
      expressed in this study, expression levels of many genes associated with skeletal
      organic matrix composition and organization were higher in light conditions. This
      implies that the rate of organic matrix synthesis is one factor limiting
      calcification at night. Thus, LEC during the day is likely to be a consequence of
      increases in both matrix synthesis and the supply of precursor molecules as a
      result of photosynthetic activity. 

PMID- 26198297
TI  - Perioperative changes in PIVKA-II.
AB  - BACKGROUND AND AIMS: Proteins induced by vitamin K absence for factor II (PIVKA
      II) is an enzyme-linked immunosorbent assay that monitors uncarboxylated
      prothrombin and responds to vitamin K deficits prior to changes in the
      prothrombin test. The aim of this project was to study perioperative PIVKA-II
      changes during various types of surgery in a prospective observational study.
      METHODS: Patients undergoing abdominal or orthopaedic surgery were included.
      Blood was sampled on the day of surgery (preoperatively) and up to 5 days after
      surgery. The activated partial thromboplastin time, Quick and Owren prothrombin
      times were analyzed, together with PIVKA-II. RESULTS: Thirty-nine patients were
      included, 27 +male and 12 +female. All but 7 +patients had elevated PIVKA-II
      levels preoperatively. PIVKA-II levels had already increased significantly (p <
      0.017) on day 1 after surgery as compared to presurgery plasma levels. The median
      PIVKA-II was highest on day 5. Routine tests were mostly normal. No significant
      difference in PIVKA-II was seen when comparing patients undergoing abdominal
      versus orthopaedic surgeries. There was no significant correlation between PIVKA
      II and routine coagulation tests. Patients with anterior resection, emergency
      laparotomy and emergency hip fractures had higher postoperative increases, which
      could be linked to increased gastrointestinal recovery times, paralytic ileus,
      peritonitis and comorbidities. CONCLUSIONS: PIVKA-II levels increase during the
      perioperative period, despite mostly normal routine coagulation tests. Pre- and
      perioperative vitamin K supplementation in patients with elevated PIVKA-II levels
      should be studied, and its clinical significance be defined in future studies.

PMID- 26198298
TI  - Idiopathic Ophthalmodynia and Idiopathic Rhinalgia: A Prospective Series of 16
      New Cases.
AB  - BACKGROUND: Idiopathic ophthalmodynia and idiopathic rhinalgia were described a
      few years ago. These conditions seem specific pain syndromes with a distinctive
      location in the eye or in the nose. We aimed to present a new prospective series
      in order to verify the consistency of these syndromes. METHODS: We performed a
      descriptive study of all patients referred to our regional neurologic clinics
      from 2010 to 2014 because of facial pain exclusively felt in the eye or in the
      nose fulfilling the proposed diagnostic criteria for idiopathic ophthalmodynia
      and idiopathic rhinalgia. RESULTS: There were 9 patients with idiopathic
      ophthalmodynia and 7 patients with idiopathic rhinalgia, with a clear female
      preponderance, and a mean age at onset in the fifth decade. The pain was usually
      moderate and the temporal pattern was generally chronic. Only one patient
      reported accompaniments (hypersensitivity to the light and to the flow of air in
      the symptomatic eye). Preventive treatment with amitriptyline, pregabalin, or
      gabapentin was partially or totally effective. CONCLUSIONS: The clinical features
      of this new series parallels those of the original description, thus indicating
      that both idiopathic ophthalmodynia and idiopathic rhinalgia have clear-cut
      clinical pictures with excellent consistency both inter- and intra-individually.

PMID- 26198299
TI  - Towards an accurate prediction of the thermal stability of homologous proteins.
AB  - Protein thermostability has been the focus of growing research interests in the
      last decades since its understanding and control play important roles in the
      optimization of a wide series of bioprocesses of academic and industrial
      importance. The complexity of this issue is rooted in the fact that the
      mechanisms ensuring thermal resistance are not unique and specific, but rather
      family- or even protein-dependent. Therefore, and despite the amount of research
      already accomplished, obtaining fast and precise thermal stability predictions is
      still a challenge, especially on a large scale. This article deepens the study of
      protein thermal stability and is focused on the prediction of its best
      descriptor, the melting temperature Tm. The relations between Tm and a series of
      factors that are expected to influence the protein stability are analyzed and
      discussed. Different Tm-prediction methods that utilize these factors, sometimes
      with additional information about homologous proteins, are introduced, and their
      individual performances are evaluated. The best methods are based on temperature
      dependent statistical potentials, on the environmental temperature of the host
      organism, on the fraction of charged residues, and on the number of residues.
      They are combined to build an improved prediction method with significantly
      increased score. The root mean square deviation between the computed and
      experimental Tm-values for 45 proteins of known structure from 11 families is
      about 7 degrees C in cross-validation and decreases to 5 degrees C when 10%
      outliers are removed. The associated linear correlation coefficients are equal to
      .91 and .95, respectively. 

PMID- 26198300
TI  - MRC-5 fibroblast-conditioned medium influences multiple pathways regulating
      invasion, migration, proliferation, and apoptosis in hepatocellular carcinoma.
AB  - BACKGROUND: Carcinoma associated fibroblasts (CAFs), an important component of
      tumor microenvironment, are capable of enhancing tumor cells invasion and
      migration through initiation of epithelial-mesenchymal transition (EMT). MRC-5
      fibroblasts are one of the CAFs expressing alpha-smooth muscle actin. It is
      ascertained that medium conditioned by MRC-5 fibroblasts stimulate motility and
      invasion of breast cancer cells. However, its role in hepatocellular carcinoma
      (HCC) is less clear. The aim of our study was to investigate the effect of MRC-5
      CM on HCC and explore the underlying mechanisms. METHODS AND RESULTS: Using a
      combination of techniques, the role of MRC-5-CM in HCC was evaluated. We
      determined that MRC-5-CM induced the non-classical EMT in Bel-7402 and MHCC-LM3
      cell lines. Initiation of the non-classical EMT was mainly via quintessential
      redistribution of alpha-, beta- and gamma-catenin, P120 catenin, E-cadherin, and
      N-cadherin, rather than up-regulation of typical EMT-related transcription
      factors (i.e., Snail, Twist1, ZEB-1 and ZEB2). We also found that MRC-5-CM
      potentiated both the migration and invasion of Bel-7402 and MHCC-LM3 cells in
      mesenchymal movement mode through activation of the alpha6, beta3, beta4, beta7
      integrin/FAK pathway and upregulation of MMP2. The flow cytometric analysis
      showed that MRC-5-CM induced G1 phase arrest in Bel-7402 cells with a concomitant
      reduction of S phase cells. In contrast, MRC-5-CM induced S phase arrest in MHCC
      LM3 cells with a concomitant reduction of cells in the G2/M phase. MRC-5-CM also
      inhibited apoptosis in Bel-7402 cells while inducing apoptosis in MHCC-LM3 cells.
      CONCLUSION: Collectively, MRC-5-CM promoted HCC cell motility and invasiveness
      through initiation of the non-classical EMT, including redistribution of alpha-,
      beta- and gamma-catenin, P120 catenin, E-cadherin, and N-cadherin, activation of
      the integrin/FAK pathway, and upregulation of MMP2. Hence, MRC-5-CM exerted
      distinct roles in Bel-7402 and MHCC-LM3 cell viability by regulating cyclins,
      cyclin dependent kinases (CDKs), CDK inhibitors (CKIs), Bcl-2 family proteins and
      other unknown mechanosensors.

PMID- 26198301
TI  - Expression of imprinted genes in placenta is associated with infant
      neurobehavioral development.
AB  - Genomic imprinting disorders often exhibit delayed neurobehavioral development,
      suggesting this unique mechanism of epigenetic regulation plays a role in mental
      and neurological health. While major errors in imprinting have been linked to
      adverse health outcomes, there has been little research conducted on how moderate
      variability in imprinted gene expression within a population contributes to
      differences in neurobehavioral outcomes, particularly at birth. Here, we profiled
      the expression of 108 known and putative imprinted genes in human placenta
      samples from 615 infants assessed by the Neonatal Intensive Care Unit (NICU)
      Network Neurobehavioral Scales (NNNS). Data reduction identified 10 genes (DLX5,
      DHCR24, VTRNA2-1, PHLDA2, NPAP1, FAM50B, GNAS-AS1, PAX8-AS1, SHANK2, and
      COPG2IT1) whose expression could distinguish between newborn neurobehavioral
      profiles derived from the NNNS. Clustering infants based on the expression
      pattern of these genes identified 2 groups of infants characterized by reduced
      quality of movement, increased signs of asymmetrical and non-optimal reflexes,
      and increased odds of demonstrating increased signs of physiologic stress and
      abstinence. Overall, these results suggest that common variation in placental
      imprinted gene expression is linked to suboptimal performance on scales of
      neurological functioning as well as with increased signs of physiologic stress,
      highlighting the central importance of the control of expression of these genes
      in the placenta for neurobehavioral development. 

PMID- 26198302
TI  - Decreased secretion of Paneth cell alpha-defensins in graft-versus-host disease.
AB  - BACKGROUND: Intestinal microbial ecology is actively regulated by Paneth cell
      derived antimicrobial peptides, alpha-defensins. Graft-versus-host disease (GVHD)
      is a major complication of allogeneic hematopoietic stem cell transplantation
      (SCT). We previously demonstrated that Paneth cells are targeted by GVHD, and
      their expression of antimicrobial peptide alpha-defensins is impaired, leading to
      a loss of physiological diversity among the microflora and development of
      bloodstream infection. Herein, we evaluated whether fecal levels of alpha
      defensins could be surrogate marker of intestinal dysbiosis. METHODS: We directly
      measured alpha-defensin cryptdin-1 (Crp1) in fecal pellets of mice with GVHD by
      using a novel enzyme-linked immunosorbent assay. RESULTS: Fecal levels of Crp1
      were significantly decreased in mice with GVHD but unchanged in mice without GVHD
      after SCT. These were correlated with intestinal flora diversity. CONCLUSION: We
      demonstrate a link between reduced secretion of Paneth cell alpha-defensins and
      dysbiosis of intestinal flora in GVHD. Fecal levels of alpha-defensins could be
      surrogate markers for intestinal microbial homeostasis.

PMID- 26198303
TI  - OrderRex: clinical order decision support and outcome predictions by data-mining
      electronic medical records.
AB  - OBJECTIVE: To answer a "grand challenge" in clinical decision support, the
      authors produced a recommender system that automatically data-mines inpatient
      decision support from electronic medical records (EMR), analogous to Netflix or
      Amazon.com's product recommender. MATERIALS AND METHODS: EMR data were extracted
      from 1 year of hospitalizations (>18K patients with >5.4M structured items
      including clinical orders, lab results, and diagnosis codes). Association
      statistics were counted for the ~1.5K most common items to drive an order
      recommender. The authors assessed the recommender's ability to predict hospital
      admission orders and outcomes based on initial encounter data from separate
      validation patients. RESULTS: Compared to a reference benchmark of using the
      overall most common orders, the recommender using temporal relationships improves
      precision at 10 recommendations from 33% to 38% (P < 10(-10)) for hospital
      admission orders. Relative risk-based association methods improve inverse
      frequency weighted recall from 4% to 16% (P < 10(-16)). The framework yields a
      prediction receiver operating characteristic area under curve (c-statistic) of
      0.84 for 30 day mortality, 0.84 for 1 week need for ICU life support, 0.80 for 1
      week hospital discharge, and 0.68 for 30-day readmission. DISCUSSION: Recommender
      results quantitatively improve on reference benchmarks and qualitatively appear
      clinically reasonable. The method assumes that aggregate decision making
      converges appropriately, but ongoing evaluation is necessary to discern common
      behaviors from "correct" ones. CONCLUSIONS: Collaborative filtering recommender
      algorithms generate clinical decision support that is predictive of real practice
      patterns and clinical outcomes. Incorporating temporal relationships improves
      accuracy. Different evaluation metrics satisfy different goals (predicting likely
      events vs. "interesting" suggestions).

PMID- 26198304
TI  - SMART on FHIR Genomics: facilitating standardized clinico-genomic apps.
AB  - BACKGROUND: Supporting clinical decision support for personalized medicine will
      require linking genome and phenome variants to a patient's electronic health
      record (EHR), at times on a vast scale. Clinico-genomic data standards will be
      needed to unify how genomic variant data are accessed from different sequencing
      systems. METHODS: A specification for the basis of a clinic-genomic standard,
      building upon the current Health Level Seven International Fast Healthcare
      Interoperability Resources (FHIR(r)) standard, was developed. An FHIR application
      protocol interface (API) layer was attached to proprietary sequencing platforms
      and EHRs in order to expose gene variant data for presentation to the end-user.
      Three representative apps based on the SMART platform were built to test end-to
      end feasibility, including integration of genomic and clinical data. RESULTS:
      Successful design, deployment, and use of the API was demonstrated and adopted by
      HL7 Clinical Genomics Workgroup. Feasibility was shown through development of
      three apps by various types of users with background levels and locations.
      CONCLUSION: This prototyping work suggests that an entirely data (and web)
      standards-based approach could prove both effective and efficient for advancing
      personalized medicine.

PMID- 26198305
TI  - Big biomedical data as the key resource for discovery science.
AB  - Modern biomedical data collection is generating exponentially more data in a
      multitude of formats. This flood of complex data poses significant opportunities
      to discover and understand the critical interplay among such diverse domains as
      genomics, proteomics, metabolomics, and phenomics, including imaging, biometrics,
      and clinical data. The Big Data for Discovery Science Center is taking an "-ome
      to home" approach to discover linkages between these disparate data sources by
      mining existing databases of proteomic and genomic data, brain images, and
      clinical assessments. In support of this work, the authors developed new
      technological capabilities that make it easy for researchers to manage,
      aggregate, manipulate, integrate, and model large amounts of distributed data.
      Guided by biological domain expertise, the Center's computational resources and
      software will reveal relationships and patterns, aiding researchers in
      identifying biomarkers for the most confounding conditions and diseases, such as
      Parkinson's and Alzheimer's. 

PMID- 26198306
TI  - Long-term effects of laparoscopic sleeve gastrectomy versus roux-en-Y gastric
      bypass for the treatment of Chinese type 2 diabetes mellitus patients with body
      mass index 28-35 kg/m(2).
AB  - BACKGROUND: To compare long term effects of two bariatric procedures for Chinese
      type 2 diabetes mellitus (T2DM) patients with a body mass index (BMI) of 28-35
      kg/m(2). METHODS: Sixty four T2DM patients with Glycated hemoglobin A1c (HbA1c) ?
      7.0 % were randomly assigned to receive laparoscopic sleeve gastrectomy (SG) or
      Roux-en-Y gastric bypass (RYGB) procedure. Weight, percentage of excess weight
      loss (%EWL), BMI, waist circumference, HbA1c, fasting blood glucose (FBG), and C
      peptide were measured. Serum lipid levels were also measured during three-year
      postoperative follow-up visits. RESULTS: Fifty five patients completed the 36
      month follow-up. Both groups had similar baseline anthropometric and biochemical
      measures. At the end point, 22 patients (78.6 %) in SG group and 23 patients
      (85.2 %) in RYGB group achieved complete remission of diabetes mellitus with
      HbA1c < 6.0 % (P = 0.525) and without taking diabetic medications, and 25
      patients in each group (89.3 % vs. 92.6 %) gained successful treatment of
      diabetes with HbA1c?6.5 % (P = 0.100). Change in HbA1c, FBG and C peptide were
      comparable in the two groups. The RYGB group had significantly greater weight
      loss than the SG group [percentage of total weight loss (%TWL) of 31.0 % vs. 27.1
      % (P = 0.049), %EWL of 92.3 % vs. 81.9 % (P = 0.003), and change in BMI of 11.0
      vs. 9.1 kg/m(2)(P = 0.017), respectively]. Serum lipids in each group were also
      greatly improved. CONCLUSION: In this three-year study, SG had similar positive
      effects on diabetes and dyslipidemia compared to RYGB in Chinese T2DM patients
      with BMI of 28-35 kg/m(2). Longer term follow-ups and larger sample studies are
      needed to confirm these outcomes, however.

PMID- 26198307
TI  - Why investigate urban health indicators?

PMID- 26198308
TI  - Physical disruption of oral biofilms by sodium bicarbonate: an in vitro study.
AB  - OBJECTIVES: Sodium bicarbonate has been shown clinically to be efficacious at
      removing dental plaque; however, its effect of mechanism against biofilms has not
      been evaluated in vitro. Here, we used a well-established in vitro plaque biofilm
      model to investigate the disruption of dental plaque biofilms. METHODS: Biofilms
      were grown in a constant depth film fermentor for up to 14 days. The fermentor
      was inoculated with pooled human saliva and growth maintained with artificial
      saliva. After various time points, replicate biofilms were removed and subjected
      to treatment at varying concentrations of sodium bicarbonate. Disruption of the
      plaque was assessed by viable counts and microscopy. RESULTS: The viable count
      results showed that younger biofilms were less susceptible to the action of
      sodium bicarbonate; however, biofilms of 7 days and older were increasingly
      susceptible to the material with the oldest biofilms being the most susceptible.
      Sixty-seven percentage of sodium bicarbonate slurry was able to reduce the number
      of organisms present by approx. 3 log10 . These quantitative data were
      corroborated qualitatively with both confocal and electron microscopy, which both
      showed substantial qualitative removal of mature biofilms. CONCLUSIONS: The
      results from this study have shown that sodium bicarbonate is able to disrupt
      mature dental plaque grown in vitro and that its reported efficacy in maintaining
      oral hygiene may be related to this key factor.

PMID- 26198309
TI  - Detection of a novel KIR3DL1*0150210 allele by sequencing.
AB  - KIR3DL1*0150210 has seven point mutations compared to the common Asian allele
      KIR3DL1*0150201. 

PMID- 26198311
TI  - Molecular mechanism of water permeation in a helium impermeable graphene and
      graphene oxide membrane.
AB  - Layers of graphene oxide (GO) are found to be good for the permeation of water
      but not for helium (Science, 2012, 335(6067), 442-444) suggesting that the GO
      layers are dynamic in the formation of a permeation route depending on the
      environment they are in (i.e., water or helium). To probe the microscopic origin
      of this observation we calculate the potential of mean force (PMF) of GO sheets
      (with oxidized and reduced parts), with the inter-planar distance as a reaction
      coordinate in helium and water. Our PMF calculation shows that the equilibrium
      interlayer distance between the oxidized part of the GO sheets in helium is at
      4.8 A leaving no space for helium permeation. In contrast, the PMF of the
      oxidized part of the GO in water shows two minima, one at 4.8 A and another at
      6.8 A, corresponding to no water and a water filled region, thus giving rise to a
      permeation path. The increased electrostatic interaction between water with the
      oxidized part of the sheet helps the sheet open up and pushes water inside. Based
      on the entropy calculations for water trapped between graphene sheets and
      oxidized graphene sheets at different inter-sheet spacings, we also show the
      thermodynamics of filling. 

PMID- 26198310
TI  - Blood pressure and mortality: using offspring blood pressure as an instrument for
      own blood pressure in the HUNT study.
AB  - Given that observational associations may be inaccurate, we used offspring blood
      pressure (BP) to provide alternative estimates of the associations between own BP
      and mortality. Observational associations between BP and mortality, estimated as
      hazard ratios (HRs) from Cox regression, were compared to HRs obtained using
      offspring BP as an instrumental variable (IV) for own BP (N = 32,227 mother
      offspring and 27,535 father-offspring pairs). Observationally, there were
      positive associations between own BP and mortality from all-causes,
      cardiovascular disease (CVD), coronary heart disease (CHD), stroke and diabetes.
      Point estimates of the associations between BP and mortality from all-causes, CVD
      and CHD were amplified in magnitude when using offspring BP as an IV. For
      example, the HR for all-cause mortality per standard deviation (SD) increase in
      own systolic BP (SBP) obtained in conventional observational analyses increased
      from 1.10 (95% CI: 1.09-1.12; P < 0.0001) to 1.31 (95% CI: 1.19-1.43; P <
      0.0001). Additionally, SBP was positively associated with diabetes and cancer
      mortality (HRs: 2.00; 95% CI: 1.12-3.35; P = 0.02 and 1.20; 95% CI: 1.02-1.42; P
      = 0.03, respectively), and diastolic BP (DBP) with stroke mortality (HR: 1.30;
      95% CI: 1.02-1.66; P = 0.03). Results support positive associations between BP
      and mortality from all-causes, CVD, and CHD, SBP on cancer mortality, and DBP on
      stroke mortality. 

PMID- 26198312
TI  - Acetamides: chemotherapeutic agents for inflammation-associated cancers.
AB  - Now clear evidences are available to support the hypothesis that inflammation
      accelerates the conditions including events and molecules that reach to various
      types of cancers. Inflammation is a normal response to infection containing the
      innate and adaptive immune systems. However, when allowed to continue,
      unresolved, perturbation of cellular microenvironment takes place; therefore, it
      leads to adaptations in genes that are linked to cancer. In addition, a lot of
      data are accessible confirming the concept that tumour microenvironment is
      orchestrated by various inflammatory cells and goes to neoplastic process and
      finally invasion, migration and metastasis. However, infiltrations of leucocytes
      lead to angiogenesis, propagation and invasion. An inflammatory microenvironment
      that perhaps fostering impact of angiogenesis include cytokines, chemokines,
      enzymes and growth factors that play key role for expansion and invasion of
      cancer cells. This insight highlights the pathogenesis of inflammation-associated
      cancers and also touches and fosters the role of acetamides for the treatment and
      chemoprevention of carcinomas that are allied with inflammation. 

PMID- 26198313
TI  - Are pharmacogenomic biomarkers an effective tool to predict taxane toxicity and
      outcome in breast cancer patients? Literature review.
AB  - PURPOSE: Breast cancer is a heterogeneous disease, characterized by various
      molecular phenotypes that correlate with different prognosis and response to
      treatments. Taxanes are some of the most active chemotherapeutic agents for
      breast cancer; however, their utilization is limited, due to hematologic and
      cumulative neurotoxicity on treated patients. To understand why only some
      patients experience severe adverse effects and why patients respond and develop
      resistance with different rates to taxane therapy, the metabolic pathways of
      these drugs should be completely unraveled. The variant forms of several genes,
      related to taxane pharmacokinetics, can be indicative markers of clinical
      parameters, such as toxicity or outcome. METHODS: The search of the data has been
      conducted through PubMed database, presenting clinical data, clinical trials and
      basic research restricted to English language until June 2015. RESULTS: We
      studied the literature in order to find any possible association between the
      major pharmacogenomic variants and specific taxane-related toxicity and patient
      outcome. We found that the data of these studies are sometimes discordant, due to
      both the small number of enrolled patients and the heterogeneity of the examined
      population. CONCLUSIONS: Among all analyzed genes, only CYP1B1 and ABCB1 resulted
      the strongest candidates to become biomarkers of clinical response to taxane
      therapy in breast cancer, although their utilization still remains an
      experimental procedure. In the future, greater studies on genetic polymorphisms
      should be performed in order to identify differentiating signatures for patients
      with higher toxicity and with resistant or responsive outcome, before the
      administration of taxanes.

PMID- 26198314
TI  - Modeling and simulations relating overall survival to tumor growth inhibition in
      renal cell carcinoma patients.
AB  - PURPOSE: To assess the link between tumor growth inhibition (TGI) and overall
      survival (OS) based on historical renal cell carcinoma (RCC) data. To illustrate
      how simulations can help to identify TGI thresholds based on target OS benefit
      [i.e., hazard ratio (HR) compared with standard of care] to support new drug
      development in RCC. METHODS: Tumor size (TS) data were modeled from 2552 patients
      with first-line or refractory RCC who received temsirolimus, interferon,
      sunitinib, sorafenib or axitinib in 10 Phase II or Phase III studies. Three model
      based TGI metrics estimates [early tumor shrinkage (ETS) at week 8, 10 or 12,
      time to tumor growth (TTG) and growth rate] as well as baseline prognostic
      factors were tested in multivariate lognormal models of OS. Model performance was
      evaluated by posterior predictive check of the OS distributions and hazard ratio
      across treatments. RESULTS: TTG was the best TGI metric to predict OS. However,
      week 8 ETS had a satisfactory performance and was employed in order to maximize
      clinical utilization. The week 8 ETS to OS model was then used to simulate
      clinically relevant ETS thresholds for future Phase II studies with
      investigational treatments. CONCLUSIONS: The published OS model and resultant
      simulations can be leveraged to support Phase II design and predict expected OS
      and HR (based on early observed TGI data obtained in Phase II or Phase III
      studies), thereby informing important mRCC development decisions, e.g., Go/No Go
      and dose regimen selection.

PMID- 26198315
TI  - Lower antioxidative capacity of multidrug-resistant cancer cells confers
      collateral sensitivity to protoflavone derivatives.
AB  - PURPOSE: Multidrug resistance (MDR) may develop due to a series of adaptive
      responses under a new stress conditions, such as chemotherapy. Novel strategies
      are urgently needed to fight MDR in cancer, and chemotherapeutics that are
      selective for MDR cancer cells offer a promising approach. Certain protoflavones
      were previously found to have potential in this regard. METHODS: Cytotoxicity of
      six protoflavones was assessed in different P-glycoprotein overexpressing MDR
      cancer cell lines and in their non-MDR counterparts. The impacts of compound 5, 6
      methylprotoflavone previously published and a new derivative, 6-bromoprotoflavone
      (compound 6), on the cell cycle distribution were evaluated, and 6 was also
      studied for its potential to regulate the intracellular antioxidative capacity.
      RESULTS: Protoflavones showed a significant cytotoxicity against all cancer cell
      lines and selectivity toward MDR cancer cells adapted to conventional
      chemotherapeutics. Inverse sensitivity versus MDR selectivity pattern was
      observed. Treatment with H2O2 showed that MDR cancer cells are more vulnerable to
      oxidative stress. Compounds 5 and 6 significantly decreased the portion of MDR
      cells in the G1 phase. The levels of reactive oxygen and nitrogen species
      (ROS/RNS) between MDR and non-MDR cells significantly differed upon exposure to
      6, accompanied by changes in the glutathione (GSH) levels and in the expression
      of manganese superoxide dismutase (MnSOD), glutathione-S-transferase pi (GST pi)
      and hypoxia-inducible factor-1alpha (HIF-1alpha). CONCLUSIONS: Our results
      suggest that MDR cancer cells can be more vulnerable to the pro-oxidative
      activity of protoflavones due to an impaired antioxidative defense that might
      arise during the adaptation processes provoked by chemotherapy.

PMID- 26198316
TI  - A phase II study of S-1, oxaliplatin, oral leucovorin, and bevacizumab
      combination therapy (SOLA) in patients with unresectable metastatic colorectal
      cancer.
AB  - PURPOSE: Adding leucovorin to fluorouracil is known to improve response rate and
      overall survival in first-line chemotherapy for metastatic colorectal cancer
      (mCRC). The present multicenter phase II study evaluated the efficacy and safety
      of S-1, oxaliplatin, oral leucovorin, and bevacizumab combination therapy (SOLA).
      METHODS: Patients with unresectable and untreated mCRC received S-1 (40-60 mg
      bid) plus leucovorin (25 mg bid) orally for 1 week, and oxaliplatin (85 mg/m(2))
      and bevacizumab (5 mg/kg) intravenously on day 1, every 2 weeks. Efficacy
      endpoints, including the response rate (the primary endpoint) and progression
      free survival, were assessed by an independent review committee. RESULTS: Of the
      29 eligible patients, 25 patients (86%) had a partial response [95% confidence
      interval (CI) 68-96%] and the remaining four patients showed stable disease with
      a trend toward tumor shrinkage. The median progression-free survival was 15
      months (95% CI 10-26 months). The median overall survival was not reached after a
      median follow-up time of 34 months. The 3-year survival rate was 54%. Curative
      resections of metastatic lesions were performed in eight patients (28%). Common
      grade 3 or 4 adverse events were neutropenia (20%), hypertension (23%), anorexia
      (20%), fatigue (17%), diarrhea (10%), and peripheral sensory neuropathy (53%).
      CONCLUSIONS: The SOLA therapy showed excellent efficacy and tolerable toxicities
      except for peripheral sensory neuropathy in patients with mCRC. Since oxaliplatin
      induced neuropathy can be alleviated by modifying its administration, SOLA is a
      promising candidate regimen to be compared with FOLFOX plus bevacizumab in a
      future phase III trial. CLINICAL TRIAL NUMBER: JapicCTI-090881.

PMID- 26198317
TI  - Computational Prediction of One-Step Synthesis of Seven-membered Fused Rings by
      (5+2) Cycloaddition Utilising Cycloalkenes.
AB  - The (5+2) cycloaddition reaction utilising cycloalkenes is rare, although it is
      one of the most efficient methods of constructing seven-membered fused rings
      because of its high atom- and step-economy. In this study, we used quantum
      mechanical calculations to predict the plausibility of using the Rh-catalysed
      intermolecular (5+2) cycloaddition of 3-acyloxy-1,4-enynes and cycloalkenes to
      produce fused seven-membered carbocycles. The calculation results suggest a
      convenient, highly efficient and energetically practical approach. Strained
      cycloalkenes, such as cyclopropene, have been predicted to be active, and the
      desired bicyclic product should be favoured, accompanied by the formation of
      byproducts from rearrangement reactions. The energy barriers of the alkene
      insertion step were analysed by the distortion/interaction model to disclose the
      origins of the different reactivities of cycloalkenes with different ring sizes. 

PMID- 26198318
TI  - Anisotropic bias dependent transport property of defective phosphorene layer.
AB  - Phosphorene is receiving great research interests because of its peculiar
      physical properties. Nonetheless, no systematic studies on the transport
      properties modified due to defects have been performed. Here, we present the
      electronic band structure, defect formation energy and bias dependent transport
      property of various defective systems. We found that the defect formation energy
      is much less than that in graphene. The defect configuration strongly affects the
      electronic structure. The band gap vanishes in single vacancy layers, but the
      band gap reappears in divacancy layers. Interestingly, a single vacancy defect
      behaves like a p-type impurity for transport property. Unlike the common belief,
      we observe that the vacancy defect can contribute to greatly increasing the
      current. Along the zigzag direction, the current in the most stable single
      vacancy structure was significantly increased as compared with that found in the
      pristine layer. In addition, the current along the armchair direction was always
      greater than along the zigzag direction and we observed a strong anisotropic
      current ratio of armchair to zigzag direction. 

PMID- 26198320
TI  - MERS-CoV: Where Are We Now?

PMID- 26198321
TI  - Long-term Outcomes of Medical Therapy Versus Coronary Revascularisation in
      Patients with Intermediate Stenoses Guided by Pressure Wire.
AB  - INTRODUCTION: This study aimed to examine the long-term clinical outcomes of
      coronary fractional flow reserve (FFR)-guided percutaneous coronary intervention
      (PCI) in a real-world population in an Asian tertiary centre. MATERIALS AND
      METHODS: All patients who underwent FFR measurement for intermediate coronary
      lesions in our centre from June 2002 to December 2009 were enrolled. A threshold
      of FFR <=0.75 was used for revascularisation. All the patients were prospectively
      followed-up for major adverse cardiac events (MACE) of death, myocardial
      infarction (MI), target vessel revascularisation (TVR) and stent thrombosis.
      RESULTS: Based on FFR measurement, 368 (57%) patients were treated medically
      while 278 (43%) underwent revascularisation. At a mean follow-up duration of 29.7
      +/- 16 months, 53 (14.4%) patients in the medical therapy group and 32 (11.5%)
      patients in the revascularised group experienced MACE (P = 0.282). There were no
      statistical differences in all the clinical endpoints between the 2 groups.
      CONCLUSION: Medical therapy based on FFR measurement is associated with low
      incidences of MACE at long-term follow-up.

PMID- 26198322
TI  - Prevalence of Chronic Kidney Disease in Adults with Type 2 Diabetes Mellitus.
AB  - INTRODUCTION: Diabetes mellitus (DM) is a major cause of chronic kidney disease
      (CKD). The epidemiology of CKD secondary to type 2 DM (T2DM) (i.e. diabetic
      nephropathy (DN)) has not been well studied in Singapore, a multi-ethnic Asian
      population. We aimed to determine the prevalence of CKD in adult patients with
      T2DM. MATERIALS AND METHODS: We conducted a cross-sectional study on patients (n
      = 1861) aged 21 to 89 years with T2DM who had attended the DM centre of a single
      acute care public hospital or a primary care polyclinic between August 2011 and
      November 2013. Demographic and clinical data were obtained from patients using a
      standard questionnaire. Spot urine and fasting blood samples were sent to an
      accredited hospital laboratory for urinary albumin, serum creatinine, HbA1c and
      lipid measurement. CKD was defined and classified using the 2012 Kidney Disease:
      Improving Global Outcomes (KDIGO) guidelines and classification. RESULTS: The
      distribution by risk of adverse CKD outcomes was: low risk, 47%; moderate risk,
      27.2%; high risk, 12.8%; and very high risk, 13%. The prevalence of CKD in
      patients with T2DM was 53%. Variables significantly associated with CKD include
      neuropathy, blood pressure >=140/80 mmHg, triglycerides >=1.7 mmol, body mass
      index, duration of diabetes, HbA1c >=8%, age, cardiovascular disease, and
      proliferative retinopathy. CONCLUSION: CKD was highly prevalent among patients
      with T2DM in Singapore. Several risk factors for CKD are well recognised and
      amenable to intervention. Routine rigorous screening for DN and enhanced
      programme for global risk factors reduction will be critical to stem the tide of
      DN.

PMID- 26198319
TI  - A draft network of ligand-receptor-mediated multicellular signalling in human.
AB  - Cell-to-cell communication across multiple cell types and tissues strictly
      governs proper functioning of metazoans and extensively relies on interactions
      between secreted ligands and cell-surface receptors. Herein, we present the first
      large-scale map of cell-to-cell communication between 144 human primary cell
      types. We reveal that most cells express tens to hundreds of ligands and
      receptors to create a highly connected signalling network through multiple ligand
      receptor paths. We also observe extensive autocrine signalling with approximately
      two-thirds of partners possibly interacting on the same cell type. We find that
      plasma membrane and secreted proteins have the highest cell-type specificity,
      they are evolutionarily younger than intracellular proteins, and that most
      receptors had evolved before their ligands. We provide an online tool to
      interactively query and visualize our networks and demonstrate how this tool can
      reveal novel cell-to-cell interactions with the prediction that mast cells signal
      to monoblastic lineages via the CSF1-CSF1R interacting pair. 

PMID- 26198323
TI  - Academic Medicine Education Institute (AM.EI): Transforming the Educational
      Culture of Health Professionals.
AB  - INTRODUCTION: The Academic Medicine Education Institute (AM?EI), jointly
      established by Duke-NUS Graduate Medical School (Duke-NUS) and Singapore
      Healthcare Services (SingHealth), is a newly formed health professions education
      academy designed to cultivate best education practices and create a community of
      health professions educators. To achieve the aims of AM?EI, the needs of
      SingHealth educators have to be understood. Therefore, this study was carried out
      to assess educators' perceptions towards the current education climate and their
      academic needs. MATERIALS AND METHODS: A 28-item questionnaire consisting of free
      response, Likert-type and ranking questions was developed. The questionnaire was
      electronically distributed to 200 medical and nursing educators, and made
      available to attendees of the 2012 Singhealth Duke-NUS Scientific Congress
      through hardcopies. RESULTS: A total of 150 completed questionnaires were
      received (94 from electronic survey and 56 from Congress). Five themes emerged
      from the analysis of responses to free-response questions: 1) faculty
      development, 2) development of a community of educators, 3) recognition for
      educational efforts, 4) institutional support, and 5) better communication about
      SingHealth educational activities. Respondents were in highest agreement with the
      statements (rating of 3.7 out of 5): "The SingHealth education programmes are
      high quality", "New learning or teaching methods are welcomed in this
      institution/hospital", and "An academic appointment is important to me". The
      competencies that respondents felt to be the most important were facilitating
      discussions, presentation skills, and providing feedback (respective means = 5.1,
      5, 5 of 7). CONCLUSION: This needs assessment provided us with important insights
      regarding SingHealth medical educators' perceptions of their education
      environment and established key priorities for the AM?EI's programming efforts.

PMID- 26198324
TI  - Is the Apprehension Test Sufficient for the Diagnosis of Anterior Shoulder
      Instability in Young Patients without Magnetic Resonance Imaging (MRI)?
AB  - INTRODUCTION: The purpose of this study is to compare the sensitivities and
      positive predictive values (PPV) of the anterior apprehension test and magnetic
      resonance imaging (MRI) in the diagnosis of anterior labral tears in young
      patients with shoulder instability and to determine if surgery could be carried
      out without this investigation in selected patients. MATERIALS AND METHODS: We
      undertook a retrospective study of 168 patients aged between 15 and 30 years with
      a history of shoulder dislocation and compared the sensitivities and the PPV of
      the apprehension test with both MRI and magnetic resonance arthrograms (MRA) in
      the diagnosis of a Bankart lesion. The radiological investigations were
      interpreted by general practice radiologists and specialised musculoskeletal
      radiologists. All patients had their diagnosis confirmed by shoulder arthroscopy.
      RESULTS: Our results showed that the apprehension test was highly reliable when
      it was positive with a PPV of 96%. It was more sensitive than MRI in the
      diagnosis of a Bankart lesion. The clinical test was significantly better when a
      musculoskeletal radiologist interpreted the MRI. The MRA interpreted by a
      musculoskeletal radiologist had the highest rates of sensitivity in detecting
      Bankart lesions. The figure was similar to that for the apprehension test. There
      was no difference in the PPVs among the clinical test, the MRI and the MRA read
      by the 2 categories of radiologists. CONCLUSION: We conclude that a routine MRI
      may be unnecessary in evaluating a young patient with clinically evident anterior
      shoulder instability if the apprehension test is positive. A MRA that can be
      interpreted by a musculoskeletal radiologist will be the next best investigation
      if the clinical test is negative or equivocal.

PMID- 26198325
TI  - 27-Gauge Vitrectomy for Primary Rhegmatogenous Retinal Detachment: Is it
      Feasible?

PMID- 26198326
TI  - Single-level Anterior Corpectomy with Fusion versus 2-level Anterior Cervical
      Decompression with Fusion: A Prospective Controlled Study with 2-year Follow-up
      Using Cages for Fusion.

PMID- 26198327
TI  - Use of the Sole Flap to Convert an Above Knee Amputation to a Below Knee
      Amputation in Trauma.

PMID- 26198329
TI  - Using Vitek MALDI-TOF mass spectrometry to identify species belonging to the
      Acinetobacter calcoaceticus-Acinetobacter baumannii complex: a relevant
      alternative to molecular biology?
AB  - Acinetobacter baumannii belongs to the Acinetobacter calcoaceticus-baumannii
      complex (Acb) containing 2 other pathogenic species: Acinetobacter pittii and
      Acinetobacter nosocomialis. Identification of these bacteria remains problematic
      despite the use of matrix-assisted laser ionization time-of-flight mass
      spectrometry (MALDI-TOF MS). Here, we enriched the SARAMISTM database of the
      Vitek MS(r) plus mass spectrometer to improve the identification of species of
      the Acb complex. For each species, we incremented reference spectra. Then, a
      SuperSpectrum was created based on the selection of 40 specific masses. In a
      second step, we validated reference spectra and SuperSpectra with 100 isolates
      identified by rpoB gene sequencing. All the isolates were correctly identified by
      MALDI-TOF MS with the database we created as compared to the identifications
      obtained by rpoB sequencing. Our database enabled rapid and reliable
      identification of the pathogen species belonging to the Acb complex.
      Identification by MALDI-TOF MS with our database is a good alternative to
      molecular biology. 

PMID- 26198328
TI  - Role of DNA methylation in renal cell carcinoma.
AB  - Alterations in DNA methylation are seen in cancers and have also been examined in
      clear cell renal cell carcinoma (ccRCC). Numerous tumor suppressor genes have
      been reported to be partially or completely silenced due to hypermethylation of
      their promoters in single-locus studies, and the use of hypomethylating agents
      has been shown to restore the expression of many of these genes in vitro. In
      particular, members of the Wnt and TGF-beta pathways, pro-apoptotic genes such as
      APAF-1 and negative cell-cycle regulators such as KILLIN have been shown to be
      epigenetically silenced in numerous studies in ccRCC. Recently, TCGA analysis of
      a large cohort of ccRCC samples demonstrated that aberrant hypermethylation
      correlated with the stage and grade in kidney cancer. Our genome-wide studies
      also revealed aberrant widespread hypermethylation that affected regulatory
      regions of the kidney genome in ccRCC. We also observed that aberrant enhancer
      hypermethylation was predictive of adverse prognosis in ccRCC. Recent discovery
      of mutations affecting epigenetic regulators reinforces the importance of these
      changes in the pathophysiology of ccRCC and points to the potential of epigenetic
      modulators in the treatment of this malignancy. 

PMID- 26198330
TI  - Testosterone Induces Increase in Aquaporin (AQP)-1, 5, and 7 Expressions in the
      Uteri of Ovariectomized Rats.
AB  - Testosterone has been reported to cause a decrease in uterine fluid volume in
      which this could involve the aquaporins (AQPs). This study aimed to investigate
      effect of testosterone on uterine AQP-1, 5, and 7 expressions in order to explain
      the reported reduction in uterine fluid volume under testosterone influence.
      Ovariectomized adult female rats received peanut oil, testosterone (1 mg/kg/day),
      estrogen (0.2 ug/kg/day), or combined estrogen plus testosterone for three
      consecutive days. Other groups received 3 days estrogen followed by 2 days either
      peanut oil or testosterone with or without flutamide or finasteride. A day after
      last injection, uteri were harvested, and the levels of AQP-1, 5, and 7 messenger
      RNA (mRNA) in uterine tissue homogenates were analyzed by real-time PCR (qPCR).
      Distributions of AQP-1, 5, and 7 proteins in uterus were observed by
      immunofluorescence. Levels of AQP-1 mRNA were elevated in rats receiving either
      estrogen or testosterone-only treatment; however, levels of AQP-5 and 7 mRNAs
      were elevated in rats receiving testosterone-only treatment. In rats pre-treated
      with estrogen, testosterone treatment resulted in higher AQP-1, 5, and 7 mRNA
      levels compared to vehicle treatment. Testosterone effects were antagonized by
      flutamide but not finasteride. Immunofluorescence study showed that AQP-1 was
      highly distributed in uterine lumenal epithelium following estrogen or
      testosterone-only treatment. However, AQP-5 and 7 distributions were high in
      uterine lumenal epithelium following testosterone-only treatment. Testosterone
      induced up-regulation of AQP-1, 5, and 7 expressions in uterus could explain the
      observed reduction in uterine fluid volume as reported under this condition.

PMID- 26198331
TI  - Whose Disease Will Recur After Mastectomy for Early Stage, Node-Negative Breast
      Cancer? A Systematic Review.
AB  - Effective local control is associated with improved overall survival,
      particularly for women with early-stage cancers. No other local therapy is
      typically offered to women with T1-2 N0 breast cancer after mastectomy, although
      in select women the 5-year local recurrence rate can be as high as 20%.
      Therefore, accurately predicting the women who are at highest risk for recurrence
      after mastectomy will identify those who might benefit from more aggressive
      adjuvant treatment. A systematic search was conducted identifying risk factors
      associated with locoregional recurrence, including age, menopausal status,
      receptor status, lymphovascular invasion (LVI), margin status, use of systemic
      therapy, size, grade, and genomic classifer score. Although associations varied
      among studies, the risk factors most consistently identified were age <= 40
      years, LVI, positive/close margin, and larger tumor size. In women with multiple
      high risk factors, risk of local recurrence was as high as 20% at 10 years.
      Additional multicenter studies are needed to investigate risk factors for
      locoregional recurrence after mastectomy without radiotherapy in T1-2N0 breast
      cancer. Consideration of additional adjuvant local therapy might be warranted in
      a subset of women at high risk of local recurrence. 

PMID- 26198332
TI  - Genitourinary Syndrome of Menopause in Breast Cancer Survivors: Are We Facing New
      and Safe Hopes?
AB  - Breast cancer survivors (BCSs) often suffer from menopausal symptoms induced by
      systemic treatments, with a consequent negative effect on quality of life. Since
      the introduction of aromatase inhibitors as the standard therapy for hormone
      dependent tumors, genitourinary syndrome of menopause (GSM) has become a main
      problem for BCSs. This new terminology refers to the wide range of vaginal and
      urinary symptoms related to menopause, which can be relieved by estrogen therapy.
      Unfortunately, systemic hormone therapy is contraindicated for BCSs and also
      vaginal estrogens at standard dosage might influence the risk of recurrence
      because they cause a significant increase of circulating estrogens. Nonhormonal
      vaginal moisturizers or lubricants are the first choice for BCSs but only have
      limited and short-term efficacy. New strategies of management of GSM are now
      available, including: (1) low-dose or ultra low-dose vaginal estrogens; (2) oral
      selective estrogen receptor modulators (ospemifene); (3) androgen therapy; (4)
      physical treatment with vaginal laser; and (5) psychosocial interventions. In
      this review we discuss and analyze these different options. 

PMID- 26198333
TI  - Clinician perceptions of operating room to intensive care unit handoffs and
      implications for patient safety: a qualitative study.
AB  - BACKGROUND: Operating room (OR) to the intensive care unit (ICU) handoffs are
      known sources of medical error, yet little is known about the relationship
      between process failures and patient harm. METHODS: Interviews were conducted
      with clinicians involved in the OR-to-ICU handoff to characterize the
      relationship between handoff process failures and patient harm. Qualitative
      analysis was used to inductively identify key themes. RESULTS: A total of 38
      interviews were conducted. Dominant themes included early communication from the
      OR to the ICU, team member participation in the handoff, and relationships
      between clinicians; clinician perspectives varied depending substantially on role
      within the team. CONCLUSIONS: The findings suggest that ambiguous roles and
      conflicting expectations of team members during the OR-to-ICU handoff can
      increase risk of patient harm. Future studies should investigate early
      postoperative ICU care as outcome markers of handoff quality and the effect of
      interprofessional education on clinician adherence to interventions.

PMID- 26198334
TI  - Use of simulators to explore specialty recommendation for a palpable breast mass.
AB  - BACKGROUND: The aim of this study was to evaluate recommendation patterns of
      different specialties for the work-up of a palpable breast mass using simulated
      scenarios and clinical breast examination models. METHODS: Study participants
      were a convenience sample of physicians (n = 318) attending annual surgical,
      family practice, and obstetrics and gynecology (OB/GYN) conferences. Two
      different silicone-based breast models (superficial mass vs chest wall mass) were
      used to test clinical breast examination skills and recommendation patterns
      (imaging, tissue sampling, and follow-up). RESULTS: Participants were more likely
      to recommend mammography (P < .001) and core biopsy (P < .0001) and less likely
      to recommend needle aspiration (P < .043) and 1-month follow-up (P < .001) for
      the chest wall mass compared with the superficial mass. Family practitioners were
      less likely to recommend ultrasound (P < .001) and obstetrics and gynecologists
      were less likely to recommend mammogram (P < .006) across models. Surgeons were
      more likely to recommend core biopsy and less likely to recommend needle
      aspiration across models (P < .001). CONCLUSIONS: Recommendation patterns
      differed across the 2 models in line with existing practice guidelines.
      Additionally, differences in practice patterns between primary care and specialty
      providers may represent varying clinician capabilities, healthcare resources, and
      individual preferences. Our work shows that simulation may be used to track
      adherence to practice guidelines for breast masses.

PMID- 26198335
TI  - Invited Commentary on "The effect of mechanical bowel preparation on anastomotic
      leaks in elective left-sided colorectal resections".

PMID- 26198336
TI  - Combination of Pegylated Interferon and Nucleos(t)ide Therapy: Toward a Cure of
      Hepatitis B Virus Infection?

PMID- 26198337
TI  - Associations of SNPs located at candidate genes to bovine growth traits,
      prioritized with an interaction networks construction approach.
AB  - BACKGROUND: For most domestic animal species, including bovines, it is difficult
      to identify causative genetic variants involved in economically relevant traits.
      The candidate gene approach is efficient because it investigates genes that are
      expected to be associated with the expression of a trait and defines whether the
      genetic variation present in a population is associated with phenotypic
      diversity. A potential limitation of this approach is the identification of
      candidates. This study used a bioinformatics approach to identify candidate genes
      via a search guided by a functional interaction network. RESULTS: A functional
      interaction network tool, BosNet, was constructed for Bos taurus. Predictions for
      candidate genes were performed using the guilt-by-association principle in
      BosNet. Association analyses identified five novel markers within BosNet
      prioritized genes that had significant effects on different growth traits in
      Charolais and Brahman cattle. CONCLUSIONS: BosNet is an excellent tool for the
      identification of single nucleotide polymorphisms that are potentially associated
      with complex traits.

PMID- 26198338
TI  - The role of primary health care services to better meet the needs of Aboriginal
      Australians transitioning from prison to the community.
AB  - BACKGROUND: Aboriginal Australians are more likely than other Australians to
      cycle in and out of prison on remand or by serving multiple short sentences-a
      form of serial incarceration and institutionalisation. This cycle contributes to
      the over-representation of Aboriginal Australians in prison and higher rates of
      recidivism. Our research examined how primary health care can better meet the
      health care and social support needs of Aboriginal Australians transitioning from
      prison to the community. METHODS: Purposive sampling was used to identify 30
      interviewees. Twelve interviews were with Aboriginal people who had been in
      prison; ten were with family members and eight with community service providers
      who worked with former inmates. Thematic analysis was conducted on the
      interviewees' description of their experience of services provided to prisoners
      both during incarceration and on transition to the community. RESULTS:
      Interviewees believed that effective access to primary health care on release and
      during transition was positively influenced by providing appropriate healthcare
      to inmates in custody and by properly planning for their release. Further,
      interviewees felt that poor communication between health care providers in
      custody and in the community prior to an inmate's release, contributed to a lack
      of comprehensive management of chronic conditions. System level barriers to
      timely communication between in-custody and community providers included inmates
      being placed on remand which contributed to uncertainty regarding release dates
      and therefore difficulties planning for release, cycling in and out of prison on
      short sentences and being released to freedom without access to support services.
      CONCLUSIONS: For Aboriginal former inmates and family members, release from
      prison was a period of significant emotional stress and commonly involved
      managing complex needs. To support their transition into the community,
      Aboriginal former inmates would benefit from immediate access to culturally-
      responsive community -primary health care services. At present, however, pre
      release planning is not always available, especially for Aboriginal inmates who
      are more likely to be on remand or in custody for less than six months.

PMID- 26198339
TI  - The role of interleukin-1 beta in the pathophysiology of Schnitzler's syndrome.
AB  - INTRODUCTION: Schnitzler's syndrome (SchS) is a disabling autoinflammatory
      disorder, characterized by a chronic urticarial rash, an M-protein, arthralgia,
      and other signs of systemic inflammation. Anti-interleukin-1 (IL-1) beta
      antibodies are highly effective, but the pathophysiology is still largely
      unknown. Here we studied the effect of in-vivo IL-1 inhibition on serum markers
      of inflammation and cellular immune responses. METHODS: Eight patients with SchS
      received monthly subcutaneous (s.c.) injections with 150 mg canakinumab for six
      months. Blood was drawn for measurement of serum markers of inflammation (12
      times per patient) and for functional and phenotypic analysis of both freshly
      isolated and toll-like receptor (TLR)-ligand-stimulated peripheral blood
      mononuclear cells (PBMCs) (five times per patient). All data were compared to
      results of healthy controls. RESULTS: IL-6 levels in serum and in lysates of
      freshly isolated PBMCs and serum myeloid-related protein (MRP8)/14 and S100A12
      levels correlated with disease activity. In vitro, LPS stimulation resulted in
      higher IL-6 and IL-1 beta production in PBMCs from symptomatic SchS patients
      compared to healthy controls, whereas patient cells were relatively
      hyporesponsive to poly:IC and Pam3Cys. The mRNA microarray of PBMCs showed
      distinct transcriptomes for controls, symptomatic patients and anti-IL-1-treated
      patients. Numbers of T- and B-cell subsets as well as M-protein concentrations
      were not affected by IL-1 inhibition. Free light chain levels were elevated in 4
      out of 8 patients. CONCLUSIONS: In conclusion, patient PBMCs are hyperresponsive
      to LPS, and clinical efficacy of IL-1 beta inhibition in patients with SchS is
      associated with in-vivo and ex-vivo suppression of inflammation. Interestingly,
      patient PBMCs showed divergent responses to TLR2/6, TLR3 and TLR4 ligands. Our
      data underscore that IL-1 beta plays a pivotal role in SchS.

PMID- 26198340
TI  - Seasonal PrEP for partners of migrant miners in southern Mozambique: a highly
      focused PrEP intervention.
AB  - INTRODUCTION: To be used most effectively, pre-exposure prophylaxis (PrEP) should
      be prioritized to those at high risk of acquisition and would ideally be aligned
      with time periods of increased exposure. Identifying such time periods is not
      always straightforward, however. Gaza Province in southern Mozambique is
      characterized by high levels of HIV transmission and circular labour migration to
      mines in South Africa. A strong seasonal pattern in births is observable,
      reflecting an increase in conception in December. Given the potential for
      increased HIV transmission between miners returning in December and their
      partners in Gaza Province, PrEP use by the latter would be a useful means of HIV
      prevention, especially for couples who wish to conceive. METHODS: A mathematical
      model was used to represent population-level adult heterosexual HIV transmission
      in Gaza Province. Increased HIV acquisition among partners of miners in December,
      coinciding with the miners' return from South Africa, is represented. In addition
      to a PrEP intervention, the scale-up of treatment and recent scale-up of male
      circumcision that have occurred in Gaza are represented. RESULTS: Providing time
      limited PrEP to the partners of migrant miners, as opposed to providing PrEP all
      year, would improve the cost per infection averted by 7.5-fold. For the cost per
      infection averted to be below US$3000, at least 85% of PrEP users would need to
      be good adherers and PrEP would need to be cheaper than US$115 per person per
      year. Uncertainty regarding incidence of HIV transmission among partners of
      miners each year in December has a strong influence on estimates of cost per
      infection averted. CONCLUSIONS: Providing time-limited PrEP to partners of
      migrant miners in Gaza Province during periods of increased exposure would be a
      novel strategy for providing PrEP. This strategy would allow for a better
      prioritized intervention, with the potential to improve the efficiency of a PrEP
      intervention considerably, as well as providing important reproductive health
      benefits.

PMID- 26198342
TI  - HIV pre-exposure prophylaxis and health and community systems in the Global
      South: Thailand case study.
AB  - INTRODUCTION: Pre-exposure prophylaxis (PrEP) is recommended by the World Health
      Organization as an effective method of HIV prevention for individuals at risk for
      infection. In this paper, we describe the unique role that Thailand has played in
      the global effort to combat the HIV epidemic, including its role in proving the
      efficacy of PrEP, and discuss the opportunities and challenges of implementing
      PrEP in a middle-income country. DISCUSSION: Thailand was one of the first
      countries in the world to successfully reverse a generalized HIV epidemic.
      Despite this early success, HIV prevalence has remained high among people who
      inject drugs and has surged among men who have sex with men (MSM) and transgender
      women (TGW). Two pivotal trials that showed that the use of oral antiretroviral
      medication as PrEP can reduce HIV transmission were conducted partially or
      entirely at Thai sites. Demonstration projects of PrEP, as well as clinical
      trials of alternative PrEP regimens, began or will begin in 2014-2015 in Thailand
      and will provide additional data and experience on how to best implement PrEP for
      high-risk individuals in the community. Financing of drug costs, the need for
      routine laboratory monitoring and lack of awareness about PrEP among at-risk
      groups all present challenges to the wider implementation of PrEP for HIV
      prevention in Thailand. CONCLUSIONS: Although significant challenges to wider use
      remain, PrEP holds promise as a safe and highly effective method to be used as
      part of a combined HIV prevention strategy for MSM and TGW in Thailand.

PMID- 26198341
TI  - The promises and challenges of pre-exposure prophylaxis as part of the emerging
      paradigm of combination HIV prevention.
AB  - INTRODUCTION: Towards the end of the twentieth century, significant success was
      achieved in reducing incidence in several global HIV epidemics through ongoing
      prevention strategies. However, further progress in risk reduction was uncertain.
      For one thing, it was clear that social vulnerability had to be addressed,
      through research on interventions addressing health systems and other structural
      barriers. As soon as antiretroviral treatment became available, researchers
      started to conceive that antiretrovirals might play a role in decreasing either
      susceptibility in uninfected people or infectiousness among people living with
      HIV. In this paper we focus on the origin, present status, and potential
      contribution of pre-exposure prophylaxis (PrEP) within the combination HIV
      prevention framework. DISCUSSION: After a phase of controversy, PrEP efficacy
      trials took off. By 2015, daily oral PrEP, using tenofovir alone or in
      combination with emtricitabine, has been proven efficacious, though efficacy
      seems heavily contingent upon adherence to pill uptake. Initial demonstration
      projects after release of efficacy results have shown that PrEP can be
      implemented in real settings and adherence can be high, leading to high
      effectiveness. Despite its substantial potential, beliefs persist about
      unfeasibility in real-life settings due to stigma, cost, adherence, and potential
      risk compensation barriers. CONCLUSIONS: The strategic synergy of behavioural
      change communication, biomedical strategies (including PrEP), and structural
      programmes is providing the basis for the combination HIV prevention framework.
      If PrEP is to ever become a key component of that framework, several negative
      beliefs must be confronted based on emerging evidence; moreover, research gaps
      regarding PrEP implementation must be filled, and appropriate prioritization
      strategies must be set up. Those challenges are significant, proportional to the
      impact that PrEP implementation may have in the global response to HIV.

PMID- 26198343
TI  - Translating PrEP effectiveness into public health impact: key considerations for
      decision-makers on cost-effectiveness, price, regulatory issues, distributive
      justice and advocacy for access.
AB  - INTRODUCTION: The extraordinary feat of proving the effectiveness of oral pre
      exposure prophylaxis (PrEP) in clinical trials in different populations in a
      variety of settings may prove to have been easier than ensuring it is used well.
      Decision-makers must make difficult choices to realize the promise of
      antiretroviral prophylaxis for their countries. This paper outlines key economic,
      regulatory and distributive justice issues that must be addressed for effective
      and acceptable PrEP implementation. DISCUSSION: In considering the role that PrEP
      can play in combination prevention programmes, decision-makers must determine who
      can benefit most from PrEP, how PrEP can be provided safely and efficiently, and
      what kind of health system support will ensure successful implementation. To do
      this, they need contextualized information on disease burden by population,
      analyses of how PrEP services might best be delivered, and projections of the
      human resource and infrastructure requirements for each potential delivery model.
      There are cost considerations, varying cost-effectiveness results and regulatory
      challenges. The principles of ethics can inform thorny discussions about who
      should be prioritized for oral PrEP and how best to introduce it fairly. We
      describe the cost-effectiveness of PrEP in different populations at higher risk
      of HIV exposure, its price in low- and middle-income countries, and the current
      regulatory situation. We explore the principles of ethics that can inform
      resource allocation decision-making about PrEP anchored in distributive justice,
      at a time when universal access to antiretroviral treatment remains to be
      assured. We then highlight the role of advocacy in moving the PrEP agenda
      forward. CONCLUSIONS: The time is ripe now for decisions about whether, how and
      for whom PrEP should be introduced into a country's HIV response. It has the
      potential to contribute significantly to high impact HIV prevention if it is
      tailored to those who can most benefit from it and if current regulatory and
      pricing barriers can be overcome. Advocacy at all levels can help inform decision
      making and push the access agenda to avert HIV infections among those at highest
      risk of HIV exposure. The benefits will accrue beyond the individual level to
      slow HIV transmission at the population level.

PMID- 26198344
TI  - Pre-exposure prophylaxis in Southern Africa: feasible or not?
AB  - INTRODUCTION: Southern and Eastern Africa bear the brunt of the AIDS epidemic,
      and current prevention interventions remain inadequate. Antiretroviral-based pre
      exposure prophylaxis (PrEP) is gaining momentum as an effective prevention
      intervention. DISCUSSION: Discussions have been started on how this strategy
      could be employed in Africa such that the populations most in need can be reached
      urgently for the greatest impact. This requires the selection of specific risk
      groups and service environments in which PrEP can be distributed safely and cost
      effectively while being mindful of any ethical issues. CONCLUSIONS: Given the
      need for an integrated public health approach to this, a number of potential
      populations and opportunities for PrEP distribution exist and are discussed in
      this commentary.

PMID- 26198345
TI  - Antiretroviral pre-exposure prophylaxis implementation in the United States: a
      work in progress.
AB  - INTRODUCTION: After the initial approval of the use of tenofovir disoproxil
      fumarate-emtricitabine (TDF/FTC) by the US Food and Drug Administration in 2012
      for anti-HIV pre-exposure prophylaxis (PrEP), uptake was initially limited, but
      more recent community surveys and expert opinion suggest wider acceptance in some
      key populations. DISCUSSION: Demonstration projects are underway to determine the
      best practices in the United States to identify at-risk individuals in primary
      care and sexually transmitted disease clinics who could benefit from PrEP.
      Studies of PrEP in combination with behavioural interventions are being
      evaluated. Studies to evaluate the use of PrEP by HIV-uninfected women in HIV
      discordant couples interested in safe conception are also getting underway. The
      optimal deployment of PrEP as part of a comprehensive national HIV/AIDS strategy
      in the United States has been limited by lack of knowledge among some at-risk
      people and by some medical providers indicating that they do not feel
      sufficiently knowledgeable and comfortable in prescribing PrEP. Studies are
      underway to determine how to assist busy clinicians to determine which of their
      patients could benefit from PrEP. Although most federal health insurance
      programmes will cover most of the costs associated with PrEP, underinsured
      patients in states that have not enacted health reform face additional challenges
      in paying for PrEP medication and appropriate clinical monitoring. CONCLUSIONS:
      PrEP implementation in the United States is a work in progress, with increasing
      awareness and uptake among some individuals in key populations.

PMID- 26198346
TI  - Beyond "getting drugs into bodies": social science perspectives on pre-exposure
      prophylaxis for HIV.
AB  - Social scientists have much to contribute to the analysis of the real and
      potential contribution of pre-exposure prophylaxis (PrEP) to HIV prevention
      around the world. Beyond just a matter of clinical efficacy and getting pills
      into people's mouths, PrEP raises a number of important social-psychological
      questions that must be attended to in order to translate biomedical and clinical
      findings into uptake of PrEP among enough people at risk of HIV infection to
      produce population-level effectiveness. PrEP is a dynamic phenomenon with
      "dialectical" attributes that invite both optimism and cynicism as a desirable
      and effective HIV prevention strategy. PrEP disrupts traditional notions of
      "safe" and "unsafe" sex; it confers on its users a level of agency and control
      not generally achieved with condoms; and it affects sexual practices and sexual
      cultures in meaningful ways. As these dynamics play out in different contexts,
      and as new modes of PrEP administration emerge, it will be important for social
      scientists to be engaged in assessing their impact on PrEP implementation and
      effectiveness. 

PMID- 26198347
TI  - Pre-exposure prophylaxis for men and transgender women who have sex with men in
      Brazil: opportunities and challenges.
AB  - INTRODUCTION: The World Health Organization recently released guidelines on the
      use of pre-exposure prophylaxis (PrEP) for prevention of HIV infection among men
      and transgender women (TGW) who have sex with men based on results of randomized
      clinical trials. The aim of this commentary is to discuss the opportunities and
      challenges of incorporating PrEP into the Brazilian continuum of HIV care and
      prevention for men who have sex with men (MSM) and TGW. DISCUSSION: Key aspects
      of the AIDS epidemic among MSM and TGW in Brazil and the comprehensive Brazilian
      response to the epidemic are presented. The universal access to health care
      provided through the Brazilian Unified Health System (SUS) and the range of
      prevention and care services already available countrywide to HIV-positive
      individuals and at-risk MSM and TGW are identified as the main facilitators for
      the implementation of PrEP. Limited PrEP awareness among MSM, TGW and health care
      providers, low HIV testing frequency and low HIV risk perception among MSM and
      TGW represent the core challenges to be addressed. Data generated by
      demonstration projects in Brazil will provide an important contribution to PrEP
      rollout in Brazil. CONCLUSIONS: The implementation of PrEP in Brazil is feasible.
      A synergistic rollout of treatment as prevention and PrEP will maximize public
      health and individual benefits of the country's comprehensive response to the
      AIDS epidemic.

PMID- 26198348
TI  - Cost-effectiveness of pre-exposure prophylaxis targeted to high-risk
      serodiscordant couples as a bridge to sustained ART use in Kampala, Uganda.
AB  - INTRODUCTION: Despite scale-up of antiretroviral therapy (ART) for treating HIV
      positive persons, HIV incidence remains elevated among those at high risk such as
      persons in serodiscordant partnerships. Antiretrovirals taken by HIV-negative
      persons as pre-exposure prophylaxis (PrEP) has the potential to avert infections
      in individuals in serodiscordant partnerships. Evaluating the cost-effectiveness
      of implementing time-limited PrEP as a short-term bridge during the first six
      months of ART for the HIV-positive partner to prevent HIV transmission compared
      to increasing ART coverage is crucial to informing policy-makers considering PrEP
      implementation. METHODS: To estimate the real world delivery costs of PrEP, we
      conducted micro-costing and time and motion analyses in an open-label prospective
      study of PrEP and ART delivery targeted to high-risk serodiscordant couples in
      Uganda (the Partners Demonstration Project). The cost (in USD, in 2012) of PrEP
      and ART for serodiscordant couples was assessed, with and without research
      components, in the study setting. Using Ministry of Health costs, the cost of
      PrEP and ART provision within a government programme was estimated, as was the
      cost of providing PrEP in addition to ART. We parameterized an HIV transmission
      model to estimate the health and economic impacts of 1) PrEP and ART targeted to
      high-risk serodiscordant couples in the context of current ART use and 2)
      increasing ART coverage to 55% of HIV-positive persons with CD4 <=500 cells/uL
      without PrEP. The incremental cost-effectiveness ratios (ICERs) per HIV infection
      and disability-adjusted life year (DALY) averted were calculated over 10 years.
      RESULTS: The annual cost of PrEP and ART delivery for serodiscordant couples was
      $1058 per couple in the study setting and $453 in the government setting. The
      portion of the programme cost due to PrEP was $408 and $92 per couple per year in
      the study and government settings, respectively. Over 10 years, a programme of
      PrEP and ART for high-risk serodiscordant couples was projected to avert 43% of
      HIV infections compared to current practice with an ICER of $1340 per infection
      averted. This was comparable to ART expansion alone, which would avert 37% of
      infections with an ICER of $1452. CONCLUSIONS: Using Uganda's gross domestic
      product per capita of $1681 as a threshold, PrEP and ART for high-risk persons
      have the potential for synergistic action and are cost-effective in preventing
      HIV infections in high prevalence settings. The annual cost of PrEP in this
      programme is less than $100 per serodiscordant couple if implemented in public
      clinics.

PMID- 26198349
TI  - PrEP implementation: moving from trials to policy and practice.
AB  - INTRODUCTION: It is increasingly clear that the HIV response will not be
      sustainable if the number of infections is not significantly reduced. DISCUSSION:
      For two decades, research has been ongoing to identify new behavioural and
      biomedical strategies to prevent HIV infection. In the past few years, the
      efficacy of several new strategies has been demonstrated, including oral pre
      exposure prophylaxis (PrEP; i.e. daily use of tenofovir/emtricitabine). Because
      several social, political and logistic barriers remain, however, optimal PrEP
      implementation will require a better dissemination of new evidence in a number of
      areas and additional implementation research from various disciplinary
      perspectives (i.e. social science, policy and ethics; health systems; and
      economics, including cost-effectiveness studies). Discussion of new evidence on
      those topics, as well as case studies of potential PrEP implementation in diverse
      environments, can improve the understanding of the role that PrEP may play in
      addressing the global HIV/AIDS epidemic.In light of these needs, the Network for
      Multidisciplinary Studies in ARV-based HIV Prevention (NEMUS) and the World
      Health Organization (WHO) were honoured to co-organize a special issue of JIAS
      aimed at contributing to a scholarly discussion of current conditions surrounding
      PrEP implementation, potential impact and efficiency, social science concerns and
      the study of PrEP implementation in specific country cases. The papers included
      in this monograph identify and cover many of the main aspects of the complex yet
      promising discussions around PrEP implementation today. CONCLUSIONS: This is a
      collection of timely contributions from global leaders in HIV research and policy
      that addresses geographic diversity, uses a trans-disciplinary approach and
      covers a variety of the complex issues raised by PrEP. As this publication will
      become accessible to all, we hope that it will remain a valuable resource for
      policy makers, programme managers, researchers and activists around the world at
      a moment of a paradigm shift of the global response to HIV.

PMID- 26198350
TI  - Rethinking HIV prevention to prepare for oral PrEP implementation for young
      African women.
AB  - INTRODUCTION: HIV incidence remains high among young women in sub-Saharan Africa
      in spite of scale-up of HIV testing, behavioural interventions, antiretroviral
      treatment and medical male circumcision. There is a critical need to critique
      past approaches and learn about the most effective implementation of evidence
      based HIV prevention strategies, particularly emerging interventions such as pre
      exposure prophylaxis (PrEP). DISCUSSION: Women in sub-Saharan Africa are at
      increased risk of HIV during adolescence and into their 20s, in part due to
      contextual factors including gender norms and relationship dynamics, and limited
      access to reproductive and sexual health services. We reviewed behavioural,
      behavioural economic and biomedical approaches to HIV prevention for young
      African women, with a particular focus on the barriers, opportunities and
      implications for implementing PrEP in this group. Behavioural interventions have
      had limited impact in part due to not effectively addressing the context, broader
      sexual norms and expectations, and structural factors that increase risk and
      vulnerability. Of biomedical HIV prevention strategies that have been tested,
      daily oral PrEP has the greatest evidence for protection, although adherence was
      low in two placebo-controlled trials in young African women. Given high efficacy
      and effectiveness in other populations, demonstration projects of open-label PrEP
      in young African women are needed to determine the most effective delivery models
      and whether women at substantial risk are motivated and able to use oral PrEP
      with sufficient adherence to achieve HIV prevention benefits. CONCLUSIONS: Social
      marketing, adherence support and behavioural economic interventions should be
      evaluated as part of PrEP demonstration projects among young African women in
      terms of their effectiveness in increasing demand and optimizing uptake and
      effective use of PrEP. Lessons learned through evaluations of implementation
      strategies for delivering oral PrEP, a first-generation biomedical HIV prevention
      product, will inform development of new and less user-dependent PrEP formulations
      and delivery of an expanding choice of prevention options in HIV prevention
      programmes for young African women.

PMID- 26198352
TI  - Vogesella amnigena sp. nov., isolated from a freshwater river.
AB  - A bacterial strain, designated Npb-02T, was isolated from a freshwater river in
      Taiwan and characterized in a taxonomic study using a polyphasic approach. Cells
      of strain Npb-02T were Gram-stain-negative, aerobic, poly-beta-hydroxybutyrate
      accumulating, rod-shaped and non-motile. Growth occurred at 15-40  degrees C
      (optimum 25-30  degrees C), at pH 7.0-8.0 (optimum pH 7.0) and with 0-1 % NaCl
      (optimum 0.5 %). Phylogenetic analyses based on 16S rRNA gene sequences showed
      that strain Npb-02T belonged to the genus Vogesella and was most closely related
      to Vogesella perlucida DS-28T with sequence similarity of 98.3 %. Strain Npb-02T
      contained summed feature 3 (comprising C16 : 1omega7c and/or C16 : 1omega6c) and
      C16 : 0 as the major fatty acids. The major respiratory quinone was Q-8.The polar
      lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol, an uncharacterized aminophospholipid and an
      uncharacterized phospholipid. The genomic DNA G+C content of strain Npb-02T was
      64.1 mol%. The DNA-DNA hybridization values for strain Npb-02T with Vogesella
      perlucida DS-28T, Vogesella mureinivorans 389T and Vogesella lacus GR13T were
      less than 25 %. On the basis of phylogenetic inference and phenotypic data,
      strain Npb-02T represents a novel species of the genus Vogesella, for which the
      name Vogesella amnigena sp. nov. is proposed. The type strain is Npb-02T ( = BCRC
      80887T = LMG 28419T = KCTC 42195T).

PMID- 26198353
TI  - Evaluating reporting and process quality of publications on UNHS: a systematic
      review of programmes.
AB  - BACKGROUND: Congenital hearing loss is one of the most frequent birth defects,
      and Early Detection and Intervention has been found to improve language outcomes.
      The American Academy of Pediatrics (AAP) and the Joint Committee on Infant
      Hearing (JCIH) established quality of care process indicators and benchmarks for
      Universal Newborn Hearing Screening (UNHS). We have aggregated some of these
      indicators/benchmarks according to the three pillars of universality, timely
      detection and overreferral. When dealing with inter-comparison, relying on
      complete and standardised literature data becomes crucial. The purpose of this
      paper is to verify whether literature data on UNHS programmes have included
      sufficient information to allow inter-programme comparisons according to the
      indicators considered. METHODS: We performed a systematic search identifying UNHS
      studies and assessing the quality of programmes. RESULTS: The identified 12
      studies demonstrated heterogeneity in criteria for referring to further
      examinations during the screening phase and in identifying high-risk neonates,
      protocols, tests, staff, and testing environments. Our systematic review also
      highlighted substantial variability in reported performance data. In order to
      optimise the reporting of screening protocols and process performance, we propose
      a checklist. Another result is the difficulty in guaranteeing full respect for
      the criteria of universality, timely detection and overreferral. CONCLUSIONS:
      Standardisation in reporting UNHS experiences may also have a positive impact on
      inter-program comparisons, hence favouring the emergence of recognised best
      practices.

PMID- 26198355
TI  - Comparative adsorption of Eu(III) and Am(III) on TPD.
AB  - Comparative adsorption behaviors of Eu(III) and Am(III) on thorium phosphate
      diphosphate (TPD), i.e., Th4(PO4)4P2O7, have been studied using a batch approach
      and surface complexation model (SCM) in this study. The results showed that
      Eu(III) and Am(III) adsorption increased to a large extent with the increase in
      TPD dose. Strong pH-dependence was observed in both Eu(III) and Am(III)
      adsorption processes, suggesting that inner-sphere complexes (ISCs) were possibly
      responsible for the adsorption of Eu(III) and Am(III). Meanwhile, the adsorption
      of Eu(III) and Am(III) decreased to a different extent with the increase in ion
      strength, which was possibly related to outer-sphere complexes and/or ion
      exchange. In the presence of fulvic acid (FA), the adsorption of Eu(III) and
      Am(III) showed high enhancement mainly due to the ternary surface complexes of
      TPD-FA-Eu(3+) and TPD-FA-Am(3+). The SCM showed that one ion exchange (=S3Am/Eu)
      and two ISCs (=(XO)2Am/EuNO3 and =(YO)2Am/EuNO3) seemed more reasonable to
      quantitatively describe the adsorption edges of both Eu(III) and Am(III). Our
      findings obviously showed that Eu(III) could be a good analogue to study actinide
      behaviors in practical terms. However, it should be kept in mind that there are
      still obvious differences between the characteristics of Eu(III) and Am(III) in
      some special cases, for instance, the complex ability with organic matter and
      adsorption affinity to a solid surface.

PMID- 26198351
TI  - PrEP Implementation Science: State-of-the-Art and Research Agenda.

PMID- 26198356
TI  - A top-notch dilemma: The complex role of NOTCH signaling in osteoarthritis.
AB  - A study by Liu et al. in the current issue of Science Signaling explores the
      complex dual role of NOTCH in the etiology of osteoarthritis by comparing gain-of
      function mouse models representing aberrant pathological signaling and transient
      physiological signaling.

PMID- 26198354
TI  - Specific antibodies to Anopheles gSG6-P1 salivary peptide to assess early
      childhood exposure to malaria vector bites.
AB  - BACKGROUND: The estimates of risk of malaria in early childhood are imprecise
      given the current entomologic and parasitological tools. Thus, the utility of
      anti-Anopheles salivary gSG6-P1 peptide antibody responses in measuring exposure
      to Anopheles bites during early infancy has been assessed. METHODS: Anti-gSG6-P1
      IgG and IgM levels were evaluated in 133 infants (in Benin) at three (M3), six
      (M6), nine (M9) and 12 (M12) months of age. Specific IgG levels were also
      assessed in their respective umbilical cord blood (IUCB) and maternal blood
      (MPB). RESULTS: At M3, 93.98 and 41.35% of infants had anti-gSG6-P1 IgG and IgM
      Ab, respectively. Specific median IgG and IgM levels gradually increased between
      M3 and M6 (p < 0.0001 and p < 0.001), M6-M9 (p < 0.0001 and p = 0.085) and M9-M12
      (p = 0.002 and p = 0.03). These levels were positively associated with the
      Plasmodium falciparum infection intensity (p = 0.006 and 0.003), and inversely
      with the use of insecticide-treated bed nets (p = 0.003 and 0.3). Levels of
      specific IgG in the MPB were positively correlated to those in the IUCB (R =
      0.73; p < 0.0001) and those at M3 (R = 0.34; p < 0.0001). CONCLUSION: The
      exposure level to Anopheles bites, and then the risk of malaria infection, can be
      evaluated in young infants by assessing anti-gSG6-P1 IgM and IgG responses before
      and after 6-months of age, respectively. This tool can be useful in
      epidemiological evaluation and surveillance of malaria risk during the first year
      of life.

PMID- 26198357
TI  - A dual role for NOTCH signaling in joint cartilage maintenance and
      osteoarthritis.
AB  - Loss of NOTCH signaling in postnatal murine joints results in osteoarthritis,
      indicating a requirement for NOTCH during maintenance of joint cartilage.
      However, NOTCH signaling components are substantially increased in abundance in
      posttraumatic osteoarthritis in humans and mice, suggesting either a reparative
      or a pathological role for NOTCH activation in osteoarthritis. We investigated a
      potential dual role for NOTCH in joint maintenance and osteoarthritis by
      generating two mouse models overexpressing the NOTCH1 intracellular domain (NICD)
      within postnatal joint cartilage. The first mouse model exhibited sustained NOTCH
      activation to resemble pathological NOTCH signaling, whereas the second model had
      transient NOTCH activation, which more closely reflected physiological NOTCH
      signaling. Sustained NOTCH signaling in joint cartilage led to an early and
      progressive osteoarthritic-like pathology, whereas transient NOTCH activation
      enhanced the synthesis of cartilage matrix and promoted joint maintenance under
      normal physiological conditions. Through RNA-sequencing, immunohistochemical, and
      biochemical approaches, we identified several targets that could be responsible
      for NOTCH-mediated cartilage degradation, fibrosis, and osteoarthritis
      progression. These targets included components of the interleukin-6 (IL-6)-signal
      transducer and activator of transcription 3 (STAT3) and mitogen-activated protein
      kinase signaling pathways, which may also contribute to the posttraumatic
      development of osteoarthritis. Together, these data suggest a dual role for the
      NOTCH pathway in joint cartilage, and they identify downstream effectors of NOTCH
      signaling as potential targets for disease-modifying osteoarthritis drugs.

PMID- 26198358
TI  - Protein phosphatase 2A regulatory subunit B56alpha limits phosphatase activity in
      the heart.
AB  - Protein phosphatase 2A (PP2A) is a serine/threonine-selective holoenzyme composed
      of a catalytic, scaffolding, and regulatory subunit. In the heart, PP2A activity
      is requisite for cardiac excitation-contraction coupling and central in
      adrenergic signaling. We found that mice deficient in the PP2A regulatory subunit
      B56alpha (1 of 13 regulatory subunits) had altered PP2A signaling in the heart
      that was associated with changes in cardiac physiology, suggesting that the
      B56alpha regulatory subunit had an autoinhibitory role that suppressed excess
      PP2A activity. The increase in PP2A activity in the mice with reduced B56alpha
      expression resulted in slower heart rates and increased heart rate variability,
      conduction defects, and increased sensitivity of heart rate to parasympathetic
      agonists. Increased PP2A activity in B56alpha(+/-) myocytes resulted in reduced
      Ca(2+) waves and sparks, which was associated with decreased phosphorylation (and
      thus decreased activation) of the ryanodine receptor RyR2, an ion channel on
      intracellular membranes that is involved in Ca(2+) regulation in cardiomyocytes.
      In line with an autoinhibitory role for B56alpha, in vivo expression of B56alpha
      in the absence of altered abundance of other PP2A subunits decreased basal
      phosphatase activity. Consequently, in vivo expression of B56alpha suppressed
      parasympathetic regulation of heart rate and increased RyR2 phosphorylation in
      cardiomyocytes. These data show that an integral component of the PP2A holoenzyme
      has an important inhibitory role in controlling PP2A enzyme activity in the
      heart.

PMID- 26198360
TI  - Sparse group composition for robust left ventricular epicardium segmentation.
AB  - Left ventricular (LV) epicardium segmentation in cardiac magnetic resonance
      images (MRIs) is still a challenging task, where the a-priori knowledge like
      those that incorporate the heart shape model is usually used to derive reasonable
      segmentation results. In this paper, we propose a sparse group composition (SGC)
      approach to model multiple shapes simultaneously, which extends conventional
      sparsity-based single shape prior modeling to incorporate a-priori spatial
      constraint information among multiple shapes on-the-fly. Multiple interrelated
      shapes (shapes of epi- and endo-cardium of myocardium in the case of LV
      epicardium segmentation) are regarded as a group, and sparse linear composition
      of training groups is computed to approximate the input group. A framework of
      iterative procedure of refinement based on SGC and segmentation based on
      deformation model is utilized for LV epicardium segmentation, in which an
      improved shape-constraint gradient Chan-Vese model (GCV) acted as deformation
      model. Compared with the standard sparsity-based single shape prior modeling, the
      refinement procedure has strong robust for relative gross and not much sparse
      errors in the input shape and the initial epicardium location can be estimated
      without complicated landmark detection due to modeling spatial constraint
      information among multiple shapes effectively. Proposed method was validated on
      45 cardiac cine-MR clinical datasets and the results were compared with expert
      contours. The average perpendicular distance (APD) error of contours is 1.50+/
      0.29mm, and the dice metric (DM) is 0.96+/-0.01. Compared to the state-of-the-art
      methods, our proposed approach appealed competitive segmentation performance and
      improved robustness.

PMID- 26198361
TI  - [Clinical spectrum of patients with spontaneous retroperitoneal hematomas].
AB  - INTRODUCTION AND OBJECTIVE: Spontaneous retroperitoneal hematoma (SRH) is a
      potentially fatal clinical entity requiring immediate recognition and
      intervention. MATERIAL AND METHODS: The clinical records of 18-year-old and older
      patients admitted to the University Hospital Marques de Valdecilla from 2003 to
      2013 were reviewed. "Spontaneous" was defined as unrelated to trauma, invasive
      procedures or bleeding due to aortic aneurysm rupture. RESULTS: Thirty-four
      patients with SRH (44% were on anticoagulant drugs). One-third of cases had
      chronic renal insufficiency. Abdominal pain was the most common symptom both in
      anticoagulated and non-anticoagulated patients (80% in anticoagulated and 89% in
      non-anticoagulated patients). About one half of the patients developed shock. A
      CT scan was the most commonly performed diagnostic test, followed by abdominal
      ultrasound. Most cases were managed conservatively (80%). More than half of the
      patients (66%) restarted anticoagulation therapy after the acute event with a
      mean delay of 19 days (range 2-90 days). None of them suffered a new bleeding
      episode. CONCLUSION: Restarting the anticoagulation treatment after hematoma
      resolution seems to be a safe practice. There is an increasing frequency of SRH
      in non-anticoagulated patients.

PMID- 26198359
TI  - Reversal of diet-induced obesity and insulin resistance by inducible genetic
      ablation of GRK2.
AB  - Insulin resistance is a common feature of obesity and predisposes individuals to
      various prevalent pathological conditions. G protein (heterotrimeric guanine
      nucleotide-binding protein)-coupled receptor kinase 2 (GRK2) integrates several
      signal transduction pathways and is emerging as a physiologically relevant
      inhibitor of insulin signaling. GRK2 abundance is increased in humans with
      metabolic syndrome and in different murine models of insulin resistance. To
      support GRK2 as a potential drug target in type 2 diabetes and obesity, we
      investigated whether lowering GRK2 abundance reversed an ongoing systemic insulin
      resistant phenotype, using a mouse model of tamoxifen-induced GRK2 ablation after
      high-fat diet-dependent obesity and insulin resistance. Tamoxifen-triggered GRK2
      deletion impeded further body weight gain, normalized fasting glycemia, improved
      glucose tolerance, and was associated with preserved insulin sensitivity in
      skeletal muscle and liver, thereby maintaining whole-body glucose homeostasis.
      Moreover, when continued to be fed a high-fat diet, these animals displayed
      reduced fat mass and smaller adipocytes, were resistant to the development of
      liver steatosis, and showed reduced expression of proinflammatory markers in the
      liver. Our results indicate that GRK2 acts as a hub to control metabolic
      functions in different tissues, which is key to controlling insulin resistance
      development in vivo. These data suggest that inhibiting GRK2 could reverse an
      established insulin-resistant and obese phenotype, thereby putting forward this
      enzyme as a potential therapeutic target linking glucose homeostasis and
      regulation of adiposity.

PMID- 26198362
TI  - [Study of prognostic factors and prevalence of post-thrombotic syndrome in
      patients with deep vein thrombosis in Spain].
AB  - BACKGROUND AND OBJECTIVE: The prevalence of post-thrombotic syndrome (PTS) in
      Spain is not known accurately at present. The main objective of this study was to
      determine the prevalence of PTS and the possible prognostic factors related to
      its development and impact on quality of life. PATIENTS AND METHOD: This was an
      observational, multicenter, cross-sectional and retrospective study of patients
      who had suffered a deep vein thrombosis (DVT) between March 2010 and March 2011.
      The Villalta scale was applied as a standardized assessment of PTS at the
      enrollment visit. According to the score, distribution was: patients with PTS
      (score>4) and patients without PTS (score <=4). Subsequently, DVT data and risk
      factors were collected retrospectively. The quality of life of patients was
      evaluated. RESULTS: In total 511 patients with DVT were enrolled, of which 7
      patients were excluded as they did not meet the inclusion/exclusion criteria. The
      prevalence of PTS was 53%, with 56.2% having a mild character, 20.6% moderate,
      and 23.2% severe. The presence of risk factors for DVT including immobilization,
      hormonal therapy and obesity was significantly higher in patients with PTS than
      in patients without PTS. There were not significant differences in the location
      of the DVT. The perception of patients about their health was significantly worse
      in patients with DVT. CONCLUSIONS: The prevalence of PTS in patients with DVT is
      very high. The presence of risk factors for DVT clearly contributes to a greater
      predisposition to suffering PTS in an average time of 2 years.

PMID- 26198363
TI  - Transcranial Direct Current Stimulation for the Treatment of Chronic Tinnitus: A
      Randomized Controlled Study.
AB  - BACKGROUND: Tinnitus is an often disabling condition for which there is no
      effective therapy. Current research suggests that tinnitus may develop due to
      maladaptive plastic changes and altered activity in the auditory and prefrontal
      cortex. Transcranial direct current stimulation (tDCS) modulates brain activity
      and has been shown to transiently suppress tinnitus in trials. OBJECTIVE: To
      investigate the efficacy and safety of tDCS in the treatment of chronic
      subjective tinnitus. METHODS: In a randomized, parallel, double-blind, sham
      controlled study, the efficacy and safety of cathodal tDCS to the auditory cortex
      with anode over the prefrontal cortex was investigated in five sessions over five
      consecutive days. Tinnitus was assessed after the last session on day 5, and at
      follow-up visits 1 and 3 months post stimulation using the Tinnitus Handicap
      Inventory (THI, primary outcome measure), Subjective Tinnitus Severity Scale,
      Hospital Anxiety and Depression scale, Visual Analogue Scale, and Clinical Global
      Impression scale. RESULTS: 42 patients were investigated, 21 received tDCS and 21
      sham stimulation. There were no beneficial effects of tDCS on tinnitus as
      assessed by primary and secondary outcome measures. Effect size assessed with
      Cohen's d amounted to 0.08 (95% CI: -0.52 to 0.69) at 1 month and 0.18 (95% CI: 
      0.43 to 0.78) at 3 months for the THI. CONCLUSION: tDCS of the auditory and
      prefrontal cortices is safe, but does not improve tinnitus. Different tDCS
      protocols might be beneficial.

PMID- 26198364
TI  - Use of Computational Modeling to Inform tDCS Electrode Montages for the Promotion
      of Language Recovery in Post-stroke Aphasia.
AB  - BACKGROUND: Although pilot trials of transcranial direct current stimulation
      (tDCS) in aphasia are encouraging, protocol optimization is needed. Notably, it
      has not yet been clarified which of the varied electrode montages investigated is
      the most effective in enhancing language recovery. OBJECTIVE: To consider and
      contrast the predicted brain current flow patterns (electric field distribution)
      produced by varied 1*1 tDCS (1 anode, 1 cathode, 5 * 7 cm pad electrodes)
      montages used in aphasia clinical trials. METHODS: A finite element model of the
      head of a single left frontal stroke patient was developed in order to study the
      pattern of the cortical EF magnitude and inward/outward radial EF under five
      different electrode montages: Anodal-tDCS (A-tDCS) over the left Wernicke's area
      (Montage A) and over the left Broca's area (Montage B); Cathodal tDCS (C-tDCS)
      over the right homologue of Wernicke's area (Montage C), and of Broca's area
      (Montage D), where for all montages A-D the "return" electrode was placed over
      the supraorbital contralateral forehead; bilateral stimulation with A-tDCS over
      the left Broca's and CtDCS over the right Broca's homologue (Montage E). RESULTS:
      In all cases, the "return" electrode over the contralesional supraorbital
      forehead was not inert and influenced the current path through the entire brain.
      Montage B, although similar to montage D in focusing the current in the
      perilesional area, exerted the greatest effect over the left perilesional cortex,
      which was even stronger in montage E. CONCLUSIONS: The position and influence of
      both electrodes must be considered in the design and interpretation of tDCS
      clinical trials for aphasia.

PMID- 26198366
TI  - A Double-blind, Placebo-controlled Study of the Effects of Daily tDCS Sessions
      Targeting the Dorsolateral Prefrontal Cortex on Tinnitus Handicap Inventory and
      Visual Analog Scale Scores.

PMID- 26198365
TI  - A Comparison of Primed Low-frequency Repetitive Transcranial Magnetic Stimulation
      Treatments in Chronic Stroke.
AB  - BACKGROUND: Preceding low-frequency repetitive transcranial magnetic stimulation
      (rTMS) with a bout of high-frequency rTMS called priming potentiates the after
      effects of the former in healthy adults. The utility of primed rTMS in stroke
      remains under-explored despite its theoretical benefits in enhancing cortical
      excitability and motor function. OBJECTIVE: To ascertain the efficacy of priming
      in chronic stroke by comparing changes in cortical excitability and paretic hand
      function following three types of primed low-frequency rTMS treatments. METHODS:
      Eleven individuals with chronic stroke participated in this repeated-measures
      study receiving three treatments to the contralesional primary motor cortex in
      randomized order: 6 Hz primed 1 Hz rTMS, 1 Hz primed 1 Hz rTMS, and sham 6 Hz
      primed active 1 Hz rTMS. Within- and between-treatment differences from baseline
      in cortical excitability and paretic hand function from baseline were analyzed
      using mixed effects linear models. RESULTS: 6 Hz primed 1 Hz rTMS produced
      significant within-treatment differences from baseline in ipsilesional cortical
      silent period (CSP) duration and short-interval intracortical inhibition.
      Compared to 1 Hz priming and sham 6 Hz priming of 1 Hz rTMS, active 6 Hz priming
      generated significantly greater decreases in ipsilesional CSP duration. These
      heightened effects were not observed for intracortical facilitation or
      interhemispheric inhibition excitability measures. CONCLUSION: Our findings
      demonstrate the efficacy of 6 Hz primed 1 Hz rTMS in probing homeostatic
      plasticity mechanisms in the stroke brain as best demonstrated by differences CSP
      duration and SICI from baseline. Though 6 Hz priming did not universally enhance
      cortical excitability across measures, our findings pose important implications
      in non-invasive brain stimulation application in stroke rehabilitation.

PMID- 26198368
TI  - Pathophysiology and burden of infection in patients with diabetes mellitus and
      peripheral vascular disease: focus on skin and soft-tissue infections.
AB  - Diabetes mellitus affects 284 million adults worldwide and is increasing in
      prevalence. Accelerated atherosclerosis in patients with diabetes mellitus
      contributes an increased risk of developing cardiovascular diseases including
      peripheral vascular disease (PVD). Immune dysfunction, diabetic neuropathy and
      poor circulation in patients with diabetes mellitus, especially those with PVD,
      place these patients at high risk for many types of typical and atypical
      infections. Complicated skin and soft-tissue infections (cSSTIs) are of
      particular concern because skin breakdown in patients with advanced diabetes
      mellitus and PVD provides a portal of entry for bacteria. Patients with diabetes
      mellitus are more likely to be hospitalized with cSSTIs and to experience related
      complications than patients without diabetes mellitus. Patients with PVD
      requiring lower extremity bypass are also at high risk of surgical site and graft
      infections. Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent
      causative pathogen in cSSTIs, and may be a significant contributor to surgical
      site infections, especially in patients who are colonized with MRSA on hospital
      admission. Patients with cSSTIs and diabetes mellitus or PVD experience lower
      clinical success rates than patients without these comorbidities, and may also
      have a longer length of hospital stay and higher risk of adverse drug events.
      Clinicians should be vigilant in recognizing the potential for infection with
      multi-drug-resistant organisms, especially MRSA, in these populations and
      initiating therapy with appropriate antibiotics. 

PMID- 26198367
TI  - Smell-taste dysfunctions in extreme weight/eating conditions: analysis of
      hormonal and psychological interactions.
AB  - (1) The objective of this study is to analyze differences in smell-taste capacity
      between females in extreme weight/eating conditions (EWC) and (2) to explore the
      interaction between smell/taste capacity, gastric hormones, eating behavior and
      body mass index (BMI). The sample comprised 239 females in EWC [64 Anorexia
      nervosa (AN) and 80 age-matched healthy-weight controls, and 59 obese and 36 age
      matched healthy-weight controls]. Smell and taste assessments were performed
      through "Sniffin' Sticks" and "Taste Strips," respectively. The assessment
      measures included the eating disorders inventory-2, the symptom check list 90
      revised, and The Dutch Eating Behavior Questionnaire, as well as peptides from
      the gastrointestinal tract [Ghrelin, peptide YY, cholecystokinin]. Smell capacity
      was differentially associated across EWC groups. Smell was clearly impaired in
      obese participants and increased in AN (hyposmia in Obesity was 54.3 and 6.4 % in
      AN), but taste capacity did not vary across EWC. Ghrelin levels were
      significantly decreased in obese subjects and were related to smell impairment.
      EWC individuals showed a distinct smell profile and circulating ghrelin levels
      compared to controls. Smell capacity and ghrelin may act as moderators of
      emotional eating and BMI.

PMID- 26198369
TI  - Implementing criteria-based early switch/early discharge programmes: a European
      perspective.
AB  - Early switch (ES) from intravenous (IV) to oral antibiotic therapy programmes is
      increasingly included as a component of hospital antimicrobial stewardship
      initiatives that aim to optimize antimicrobial therapy while limiting toxicity
      and resistance. In terms of prioritizing the most cost-effective stewardship
      interventions, ES has been seen as a 'low-hanging fruit', which refers to
      selecting the most obtainable targets rather than confronting more complicated
      issues. Administration of highly bioavailable oral antibiotics should be
      considered for nearly all non-critically ill patients and has been recommended as
      an effective and safe strategy for over two decades. However, to accrue the most
      benefit from ES, it should be combined with an early discharge (ED) plan,
      protocol, or care pathway. Benefits of this combined approach include improved
      patient comfort and mobility, reduced incidence of IV-line-related adverse
      effects, reduced IV antimicrobial preparation time, decreased hospital stays,
      reduced antimicrobial purchasing and administration costs, decreased patient
      deconditioning, and shortened recovery times. Results from published studies
      document decreases in healthcare resource use and costs following implementation
      of ES programmes, which in most studies facilitate the opportunity for ED and ED
      programmes. Barriers to the implementation of these programmes include clinician
      misconceptions, practical considerations, organizational factors, and a striking
      lack of awareness of IV to oral switch guidance. These and other barriers will
      need to be addressed to maximize the effectiveness of ES and ED programmes. As
      national antimicrobial stewardship programmes dictate the inclusion of ES and ED
      programmes within healthcare facilities, programmes must be developed and success
      must be documented. 

PMID- 26198370
TI  - Comparison of vancomycin and linezolid in patients with peripheral vascular
      disease and/or diabetes in an observational European study of complicated skin
      and soft-tissue infections due to methicillin-resistant Staphylococcus aureus.
AB  - Suboptimal antibiotic penetration into soft tissues can occur in patients with
      poor circulation due to peripheral vascular disease (PVD) or diabetes. We
      conducted a real-world analysis of antibiotic treatment, hospital resource use
      and clinical outcomes in patients with PVD and/or diabetes receiving linezolid or
      vancomycin for the treatment of methicillin-resistant Staphylococcus aureus
      complicated skin and soft-tissue infections (MRSA cSSTIs) across Europe. This
      subgroup analysis evaluated data obtained from a retrospective, observational
      medical chart review study that captured patient data from 12 European countries.
      Data were obtained from the medical records of patients >= 18 years of age,
      hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and
      discharged alive by 31 July 2011. Hospital length of stay and length of treatment
      were compared between the treatment groups using inverse probability of treatment
      weights to adjust for clinical and demographic differences. A total of 485
      patients had PVD or diabetes and received treatment with either vancomycin (n =
      258) or linezolid (n = 227). After adjustment, patients treated with linezolid
      compared with vancomycin respectively had significantly shorter hospital stays
      (17.9 +/- 13.6 vs. 22.6 +/- 13.6 days; p < 0.001) and treatment durations (12.9
      +/- 7.9 vs. 16.4 +/- 8.3 days; p < 0.001). The proportions of patients prescribed
      oral, MRSA-active antibiotics at discharge were 43.2% and 12.4% of patients in
      the linezolid and vancomycin groups, respectively (p < 0.001). The reduction in
      resource use may result in lower hospital costs for patients with PVD and/or
      diabetes and MRSA cSSTIs if treated with linezolid compared with vancomycin.

PMID- 26198371
TI  - Symptomatic Cerebral Vasospasm and Delayed Cerebral Ischemia Following
      Transsphenoidal Resection of a Craniopharyngioma.
AB  - BACKGROUND: Vasospasm has been rarely described as a complication associated with
      craniopharyngioma surgery. Herein we describe a patient who developed symptomatic
      vasospasm and delayed cerebral ischemia after transsphenoidal surgery for a
      craniopharyngioma. CASE REPORT: A 67-year-old woman became drowsy 2 weeks after a
      transsphenoidal resection of a craniopharyngioma. A head computed tomography (CT)
      was unremarkable except for postoperative findings. Electroencephalogram and
      laboratory studies were within the normal limits. A repeated CT scan 48 hours
      after the initial symptoms showed bilateral infarcts in the territory of the
      anterior cerebral arteries (ACA). Transcranial Doppler (TCD) showed increased
      blood flow velocities in both anterior cerebral arteries (169 cm/second in the
      left ACA and 145 cm/second in the right ACA) and right middle cerebral artery
      (164 cm/second) compatible with vasospasm. A CT angiography confirmed the
      findings. She was treated with induced hypertension and her level of
      consciousness improved. TCD velocities normalized after 2 weeks. CONCLUSION:
      Cerebral vasospasm should be considered in the differential diagnosis of patients
      with altered neurologic status in the postoperative period following a
      craniopharyngioma resection.

PMID- 26198372
TI  - Cerebral Vasospasm and Delayed Cerebral Ischemia after Warfarin-Induced
      Subarachnoid Hemorrhage.
AB  - BACKGROUND: Subarachnoid hemorrhage (SAH) associated with anticoagulation is a
      rare event. About 30% of in-hospital patients with aneurysmal SAH develop delayed
      cerebral ischemia (DCI); however, the occurrence of vasospasm and DCI in patients
      with nonaneurysmal SAH is still controversial. METHODS: This study is a case
      report of a patient experiencing an anticoagulation-induced SAH complicated by
      vasospasm and DCI. RESULTS: A 38-year-old woman presented to our hospital with a
      sudden onset of severe headache. Head computed tomography (CT) showed bleeding in
      the posterior fossa subarachnoid space. There was no aneurysm in the CT
      angiography. The International Normalized Ratio at hospital admission was 9.
      Anticoagulation was held, and she was treated with fresh frozen plasma (15 mg/kg)
      and parenteral vitamin K. The patient remained in the intensive care unit and had
      daily transcranial Doppler (TCD) monitorization. TCD examination detected
      increased blood flow velocities in the basilar and vertebral arteries, meeting
      criteria for definitive vasospasm. CT angiography confirmed the presence of
      posterior circulation vasospasm. Magnetic resonance (MR) imaging 2 weeks after
      the bleeding showed a small area of restricted diffusion in the left superior
      cerebellar artery territory. MR angiography showed resolution of the vasospasm at
      this time point and TCD velocities normalized. CONCLUSIONS: In conclusion, this
      case report suggests that vasospasm and consequent DCI is a possible mechanism of
      secondary lesion after anticoagulation-induced SAH. To our knowledge, this is the
      first report of vasospasm and DCI due to warfarin-associated SAH.

PMID- 26198373
TI  - Low muscle mass is associated with chemotherapy-induced haematological toxicity
      in advanced non-small cell lung cancer.
AB  - BACKGROUND: Recent research suggests a significant relationship between lean body
      mass (LBM) and toxicity from chemotherapeutic agents. We investigated if higher
      drug doses per kg LBM were associated with increased toxicity in stage IIIB/IV
      non-small cell lung cancer (NSCLC) patients receiving a first-line chemotherapy
      regimen dosed according to body surface area (BSA). METHODS: Data from patients
      randomised to receive intravenous gemcitabine 1000 mg/m(2) plus orally
      vinorelbine 60 mg/m(2) days 1 and 8 in a phase III trial comparing two
      chemotherapy regimens were analysed. LBM was estimated from assessment of the
      cross-sectional muscle area at the third lumbar level (L3) on computed tomography
      images obtained before chemotherapy commenced. Common terminology criteria for
      adverse events (CTCAE) grade 3-4 haematological toxicity and dose reduction
      and/or stop of treatment after the first course of chemotherapy were defined as
      primary and secondary toxicity outcomes. RESULTS: The study sample included 153
      patients, mean age was 66 years, 55% were men, 87% had disease stage IV and 75%
      had performance status (PS) 0-1. Gemcitabine doses per kg LBM varied from 23.2 to
      53.1 mg/kg LBM, and vinorelbine doses from 1.5 to 3.3 mg/kg LBM. Higher doses of
      gemcitabine per kg LBM were significantly associated with grade 3-4
      haematological toxicity in bivariate (OR=1.12, 95% CI 1.03-1.23, p=0.008) and
      multivariate analyses (OR=1.15, 95% CI 1.01-1.29, p=0.018), as were also higher
      doses of vinorelbine per kg LBM. No significant association was found between
      drug doses per kg LBM and dose reduction and/or stop of treatment. CONCLUSION:
      The study showed that dose estimates according to BSA lead to a substantial
      variation in drug dose per kg LBM, and higher doses per kg LBM are a significant
      predictor for chemotherapy-induced haematological toxicity. The results indicate
      that taking LBM into account may lead to a better dose individualisation of
      chemotherapy.

PMID- 26198375
TI  - Energy transport mechanism in the form of proton soliton in a one-dimensional
      hydrogen-bonded polypeptide chain.
AB  - The dynamics of protons in a one-dimensional hydrogen-bonded (HB) polypeptide
      chain (PC) is investigated theoretically. A new Hamiltonian is formulated with
      the inclusion of higher-order molecular interactions between peptide groups
      (PGs). The wave function of the excitation state of a single particle is replaced
      by a new wave function of a two-quanta quasi-coherent state. The dynamics is
      governed by a higher-order nonlinear Schrodinger equation and the energy
      transport is performed by the proton soliton. A nonlinear multiple-scale
      perturbation analysis has been performed and the evolution of soliton parameters
      such as velocity and amplitude is explored numerically. The proton soliton is
      thermally stable and very robust against these perturbations. The energy
      transport by the proton soliton is more appropriate to understand the mechanism
      of energy transfer in biological processes such as muscle contraction, DNA
      replication, and neuro-electric pulse transfer on biomembranes. 

PMID- 26198376
TI  - Does the concept of lower-risk myelodysplastic syndrome need to be revisited?

PMID- 26198374
TI  - Experiences with obtaining informed consent for genomic sequencing.
AB  - Despite the increased utilization of genome and exome sequencing, little is known
      about the actual content and process of informed consent for sequencing. We
      addressed this by interviewing 29 genetic counselors and research coordinators
      experienced in obtaining informed consent for sequencing in research and clinical
      settings. Interviews focused on the process and content of informed consent;
      patients/participants' common questions, concerns and misperceptions; and
      challenges to obtaining informed consent. Content analysis of transcribed
      interviews revealed that the main challenges to obtaining consent related to the
      broad scope and uncertainty of results, and patient/participants' unrealistic
      expectations about the likely number and utility of results. Interviewees
      modified their approach to sessions according to contextual issues surrounding
      the indication for testing, type of patient, and timing of testing. With
      experience, most interviewees structured sessions to place less emphasis on
      standard elements in the consent form and technological aspects of sequencing.
      They instead focused on addressing misperceptions and helping
      patients/participants develop realistic expectations about the types and
      implications of possible results, including secondary findings. These findings
      suggest that informed consent sessions should focus on key issues that may be
      misunderstood by patients/participants. Future research should address the extent
      to which various stakeholders agree on key elements of informed consent.

PMID- 26198377
TI  - Helicobacter pylori eradication for the prevention of gastric neoplasia.
AB  - BACKGROUND: Gastric cancer is the third most common cause of cancer death
      worldwide. Individuals infected with Helicobacter pylori have a higher likelihood
      of developing gastric cancer than individuals who are not infected. Eradication
      of H. pylori in healthy asymptomatic individuals in the general population may
      reduce the incidence of gastric cancer, but the magnitude of this effect is
      unclear. OBJECTIVES: To assess the effectiveness of eradication of H. pylori in
      healthy asymptomatic individuals in the general population in reducing the
      incidence of gastric cancer. SEARCH METHODS: We identified trials by searching
      the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 11),
      MEDLINE (1946 to December 2013), and EMBASE (1974 to December 2013). We
      handsearched reference lists from trials selected by electronic searching to
      identify further relevant trials. We handsearched published abstracts from
      conference proceedings from the United European Gastroenterology Week (published
      in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001
      and 2013. We contacted members of the Cochrane Upper Gastrointestinal and
      Pancreatic Diseases Review Group and experts in the field and asked them to
      provide details of outstanding clinical trials and any relevant unpublished
      materials. SELECTION CRITERIA: We analysed randomised controlled trials comparing
      at least one week of H. pylori therapy with placebo or no treatment in preventing
      subsequent development of gastric cancer in otherwise healthy and asymptomatic H.
      pylori-positive adults. Trials had to follow up participants for at least two
      years and needed to have at least two participants with gastric cancer as an
      outcome. We defined gastric cancer as any gastric adenocarcinoma, including
      intestinal (differentiated) or diffuse (undifferentiated) type, with or without
      specified histology. DATA COLLECTION AND ANALYSIS: We collected data on incidence
      of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer,
      deaths from any cause, and adverse effects arising due to therapy. MAIN RESULTS:
      Six trials met all our eligibility criteria and provided extractable data. Three
      trials were at low risk of bias, one trial was at unclear risk, and two trials
      were at high risk of bias. Five trials were conducted in Asian populations. In
      preventing development of subsequent gastric cancer, H. pylori eradication
      therapy was superior to placebo or no treatment (6 trials, 6497 participants,
      risk ratio (RR) of developing subsequent gastric cancer 0.66; 95% confidence
      interval (CI) 0.46 to 0.95; moderate-quality evidence). Only one trial reported
      effect of eradication of H. pylori on development of subsequent oesophageal
      cancer (2 (0.2%) among 817 participants assigned to eradication therapy, compared
      with 1 (0.1%) of 813 participants allocated to placebo; RR 1.99; 95% CI 0.18 to
      21.91). The effect of H. pylori eradication on preventing death from gastric
      cancer compared with placebo or no treatment was uncertain due to wide confidence
      intervals (3 trials, 4475 participants, RR 0.67; 95% CI 0.40 to 1.11; moderate
      quality evidence). There was no evidence of an effect on all-cause mortality (4
      trials, 5253 participants, RR 1.09; 95% CI 0.86 to 1.38; moderate-quality
      evidence). Adverse events data were poorly reported. AUTHORS' CONCLUSIONS: We
      found limited, moderate-quality evidence that searching for and eradicating H.
      pylori reduces the incidence of gastric cancer in healthy asymptomatic infected
      Asian individuals, but we cannot necessarily extrapolate this data to other
      populations.

PMID- 26198378
TI  - Measuring Serum Amyloid A for Infection Prediction in Aneurysmal Subarachnoid
      Hemorrhage.
AB  - Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high rates of
      mortality and morbidity. Nosocomial infections, such as pneumonia or urinary
      tract infections, are among the main causes of worsening outcomes and death. The
      aim of this study was to discover a biomarker to predict infection in aSAH
      patients. For this purpose, the plasma of infected and noninfected patients was
      compared using quantitative mass spectrometry. The most interesting
      differentially expressed proteins were selected for validation by immunoassays on
      plasma samples taken from patients (n = 81) over 10 days of hospitalization.
      Predictive performances were established using Mann-Whitney U tests and receiver
      operating characteristic curves. Quantitative proteomics identified 17
      significantly regulated proteins. Of these, levels of serum amyloid A (SAA) were
      significantly higher in infected patients (p < 0.007). ELISA confirmed that the
      concentrations were significantly higher (p < 0.002) already at hospital
      admission in patients who subsequently developed an infection during their
      hospitalization, (AUC of 76%) for a cutoff value of 90.9 MUg/mL. Our data
      suggested that measuring SAA could be an efficient means of detecting patients
      susceptible of developing an infection during hospitalization after an aSAH. Its
      predictive capacity could lead to earlier antibiotherapy, improved patient
      management, and potentially better long-term outcomes. 

PMID- 26198379
TI  - A miniaturized electrochemical assay for homocysteine using screen-printed
      electrodes with cytochrome c anchored gold nanoparticles.
AB  - Determination of homocysteine (HcySH) is highly beneficial in human physiology
      and pathophysiology for diagnosis and prognosis of cardiovascular diseases (CVD).
      Unfortunately, the practicability of the existing methodologies for the
      determination of HcySH is limited in terms of sample requirements, preparation
      time and instrumentation cost. To overcome these limitations, we have developed a
      new miniaturized electrochemical assay for HcySH in which cytochrome c (cyt c)
      immobilized on gold nanoparticle (GNP) modified screen printed carbon electrode
      (SPE) is employed as a biosensing element. The electrochemical characterization
      of the biosensor (cyt c-GNP-SPE) shows quasi-reversible redox peaks at the
      potentials 0 and -0.2 V, confirming the cyt c binding. The methodology of
      quantification is based on the electrochemical oxidation of HcySH by the
      Fe(3+)/Fe(2+) crevice of cyt c, observed at a potential of +0.56 V. Using the
      amperometric technique, the detection limit of HcySH is found to be 0.3 +/- 0.025
      MUM in the linear range between 0.4 MUM and 700 MUM, with a sensitivity of 3.8 +/
      0.12 nA MUM(-1) cm(-2). The practical application of the present assay is
      validated through the measurement of HcySH in blood plasma samples and the
      selectivity is ensured by eliminating the impact of the common interfering
      biological substrates using a Nafion membrane. This biosensor shows striking
      analytical properties of good repeatability, reproducibility (2.85% SD) and high
      stability (83% of its initial current response after 4 weeks). This work paves
      the way for cheap, efficient and reliable point-of-care biosensors for screening
      one of the major causes of deaths both in the developed and developing countries.

PMID- 26198380
TI  - Whole-body continuously moving table fat-water MRI with dynamic B0 shimming at 3
      Tesla.
AB  - PURPOSE: The purpose of this work was to develop a rapid and robust whole-body
      fat-water MRI (FWMRI) method using a continuously moving table (CMT) with dynamic
      field corrections at 3 Tesla. METHODS: CMT FWMRI was developed at 3 Tesla with a
      multiecho golden angle (GA) radial trajectory and dynamic B0 field shimming.
      Whole-body imaging was performed with 4 echoes and superior-inferior coverage of
      1.8 meters without shims in 90 s. 716 axial images were reconstructed with GA
      profile binning followed by B0 field map generation using fast three-point seeded
      region growing fat-water separation and slice-specific 0(th) and 1(st) order shim
      calculation. Slice-specific shims were applied dynamically in a repeated CMT
      FWMRI scan in the same session. The resulting images were evaluated for field
      homogeneity improvements and quality of fat-water separation with a whole-image
      energy optimized algorithm. RESULTS: GA sampling allowed high quality whole-body
      FWMRI from multiecho CMT data. Dynamic B0 shimming greatly improved field
      homogeneity in the body and produced high quality water and fat only images as
      well as fat signal fraction and R2 * relaxivity maps. CONCLUSION: A rapid and
      robust technique for whole-body fat-water quantification has been developed with
      CMT MRI with dynamic B0 field correction. Magn Reson Med 76:183-190, 2016. (c)
      2015 Wiley Periodicals, Inc.

PMID- 26198381
TI  - Effect of wet-cold weather transportation conditions on thermoregulation and the
      development of accidental hypothermia in pullets under tropical conditions.
AB  - The present study examines onboard thermal microclimatic conditions and
      thermoregulation of pullets exposed to accidental hypothermia during wet-cold
      weather transportation conditions, and the effect of rewarming on colonic
      temperature (CT) of the birds immediately after transportation. A total of 2200
      pullets were transportation for 5 h in two separate vehicles during the
      nighttime. The last 3 h of the transportation period was characterized by heavy
      rainfall. During the precipitation period, each vehicle was covered one fourth
      way from the top-roof with a tarpaulin. The onboard thermal conditions inside the
      vehicles during transportation, which comprised ambient temperature and relative
      humidity were recorded, while humidity ratio and specific enthalpy were
      calculated. The CT of the birds was recorded before and after transportation.
      During transportation, onboard thermal heterogeneity was observed inside the
      vehicles with higher (p < 0.05) values in the front and center, and lower values
      recorded at the air inlets at the sides and rear planes. The CT values recorded
      in birds at the front and center planes were between 42.2 and 42.5  degrees C,
      indicative of mild hypothermia; while lower CT values between 28 and 38  degrees
      C were recorded at the sides and rear planes, indicative of mild to severe
      hypothermia. Several hours of gradual rewarming returned the CT to normal range.
      The result, for the first time, demonstrated the occurrence of accidental
      hypothermia in transported pullets under tropical conditions and a successful
      rewarming outcome. In conclusion, transportation of pullets during wet weather at
      onboard temperature of 18-20  degrees C induced hypothermia on birds located at
      the air inlets, which recovered fully after several hours of gradual rewarming. 

PMID- 26198382
TI  - The relative efficacy of telephone and email reminders to elicit blood donation.
AB  - The aim of the study was to test the relative efficacy of telephone and email
      reminders to trigger blood donation. A sample of 3454 donors was randomized to
      one of three conditions: phone only (n = 1176), email only (n = 1091) and phone +
      email (n = 1187). There was a higher proportion of donors who registered to give
      blood in the phone + email condition (18.45%) compared to the other two
      conditions (phone: 15.73%, P < 0.05; email: 13.20%; P < 0.001); this effect was
      apparent only in men. The phone and email conditions did not differ significantly
      (P = 0.16), suggesting equivalent efficacy.

PMID- 26198383
TI  - Segmentectomy: is minimally invasive surgery going to change a liver dogma?
AB  - Nowadays, the respective approach to hepatic resections (for malignant or benign
      liver lesions) is oriented toward minimal parenchymal resection. This surgical
      behavior is sustained by several observations that surgical margin width is not
      correlated with recurrence of malignancies. Parenchymal-sparing resection reduces
      morbidity without changing long-term results and allows the possibility of re-do
      liver resection in case of recurrence. Minimally invasive liver surgery (MILS) is
      performed worldwide and is considered a standard of care for many surgical
      procedures. MILS is associated with less blood loss, less analgesic requirements,
      and shorter length of hospital with a better quality of life. One of the more
      frequent criticisms to MILS is that it represents a more challenging approach for
      anatomical segmentectomies and that in most cases a non-anatomical resection
      could be performed with thinner resection margins compared with open surgery. But
      even in the presence of reduced surgical margins, oncological results in the
      short- and long-term follow-up seem to be the same such as open surgery. The
      purpose of this review is to try to understand whether chasing at any cost
      laparoscopic anatomical segmentectomies is still necessary whereas non-anatomical
      resections, with a parenchymal-sparing behavior, are feasible and overall
      recommended also in a laparoscopic approach. The message coming from this review
      is that MILS is opening more and more new frontiers that are still need to be
      supported by further experience. 

PMID- 26198384
TI  - Comparative effectiveness of propranolol and botulinum for the treatment of
      essential voice tremor.
AB  - OBJECTIVES/HYPOTHESIS: To assess the comparative effectiveness of botulinum toxin
      and propranolol in patients with essential vocal tremor (EVT). STUDY DESIGN:
      Individual prospective cohort study. METHODS: Study patients were recruited at
      the Emory Voice Center from patients seeking treatment for EVT. Exclusion
      criteria included current beta-blocker treatment, spasmodic dysphonia, or other
      disease that prevented the use of propranolol therapy. A 10-week washout period
      from prior botulinum toxin treatment occurred before enrollment. Patients were
      assessed via the Voice-Related Quality-Of-Life (VRQOL) questionnaire, Quality of
      life in Essential Tremor questionnaire, and blinded perceptual voice assessment.
      These assessments were made at baseline voice 2 weeks after propranolol therapy
      and 4 weeks after botulinum toxin injection. RESULTS: Eighteen patients were
      enrolled. After 2 to 4 weeks of propranolol therapy (with a maximum dosage of 60
      mg to 90 mg per day), patients report an average DeltaVRQOL of 9.31. Six patients
      report significant VRQOL improvement >10, with the rest reporting changes between
      -7.5 and 7.5. Fifteen patients were followed for at least 4 weeks after botulinum
      toxin injection, reporting an average improvement in scaled VRQOL of 22.00.
      Blinded perceptual voice assessment demonstrates an improvement in overall
      severity of tremor with botulinum toxin. CONCLUSIONS: In some patients with EVT,
      propranolol led to significant vocal improvement with no major side effects.
      Although botulinum toxin remains the gold-standard therapy for patients with EVT,
      propranolol represents a possible alternative or adjuvant therapy for certain
      patients.

PMID- 26198385
TI  - Investigation of Functionalized Poly(N,N-dimethylacrylamide)-block-polystyrene
      Nanoparticles As Novel Drug Delivery System to Overcome the Blood-Brain Barrier
      In Vitro.
AB  - In the search of new drug delivery carriers for the brain, self-assembled
      nanoparticles (NP) were prepared from poly(N,N-dimethylacrylamide)-block
      polystyrene polymer. NP displayed biocompatibility on cultured endothelial cells,
      macrophages and differentiated SH-SY5Y neuronal-like cells. The surface
      functionalization of NP with a modified fragment of human Apolipoprotein E
      (mApoE) enhanced the uptake of NP by cultured human brain capillary endothelial
      cells, as assessed by confocal microscopy, and their permeability through a
      Transwell Blood Brain Barrier model made with the same cells, as assessed by
      fluorescence. Finally, mApoE-NP embedding doxorubicin displayed an enhanced
      release of drug at low pH, suggesting the potential use of these NP for the
      treatment of brain tumors. 

PMID- 26198386
TI  - Group-based task-oriented exercises aimed at managing kinesiophobia improved
      disability in chronic low back pain.
AB  - BACKGROUND: There are still doubts concerning the clinical impact of
      multidisciplinary cognitive behavioural rehabilitation programmes conducted in
      group-based settings and about their long-term effects on subjects with chronic
      low back pain (CLBP). This randomized, parallel-group superiority-controlled
      trial aimed at evaluating the effect of such a programme on disability,
      kinesiophobia, catastrophizing, pain and quality of life in CLBP. METHODS: One
      hundred and fifty patients were randomly assigned to a 5-week group-based
      multidisciplinary programme of task-oriented exercises integrated with cognitive
      behavioural therapy mainly aimed at managing kinesiophobia (experimental group,
      75 subjects) or group-based traditional exercises (control group, 75 subjects).
      Before treatment, 5 weeks later (post-treatment), 12 and 24 months after the end
      of treatment, the Oswestry Disability Index, the Tampa Scale for Kinesiophobia,
      the Pain Catastrophizing Scale, a pain Numerical Rating Scale and the Short Form
      Health Survey were assessed. A linear mixed model for repeated measures was used
      for each outcome measure. RESULTS: Significant group (p < 0.001), time (p <
      0.001) and time-by-group interaction (p < 0.001) effects were found on
      disability, with a between-group difference (95% confidence interval) after
      training in favour of the experimental group of -10 (-12; -8). Also
      kinesiophobia, catastrophizing, pain, and quality of life improved to a
      significantly greater extent in the experimental group. The improvements of the
      experimental group were maintained at follow-ups. CONCLUSION: This light group
      based multidisciplinary cognitive behavioural rehabilitation programme was
      superior to traditional exercises in reducing disability, kinesiophobia,
      catastrophizing, and enhancing the quality of life of subjects with CLBP. The
      effects lasted for at least 2 years after the end of the intervention.

PMID- 26198387
TI  - Rational Design and Synthesis of gammaFe2 O3 @Au Magnetic Gold Nanoflowers for
      Efficient Cancer Theranostics.
AB  - An gammaFe2 O3 @Au core/shell-type magnetic gold nanoflower-based theranostic
      nano-platform is developed. It is integrated with ultrasensitive surface-enhanced
      Raman scattering imaging, high-resolution photo-acoustics imaging, real-time
      magnetic resonance imaging, and photothermal therapy capabilities. 

PMID- 26198388
TI  - Azuki bean (Vigna angularis) extract stimulates the phosphorylation of AMP
      activated protein kinase in HepG2 cells and diabetic rat liver.
AB  - BACKGROUND: The activation of AMP-activated protein kinase (AMPK) has a
      beneficial effect on hyperglycaemia. The aim of this study was to examine whether
      an azuki bean (Vigna angularis) extract (ABE) stimulates the AMPK or insulin
      signalling pathways in a liver cell line in response to hyperglycaemia, as well
      as in a diabetic rat liver. RESULTS: HepG2 cells were incubated with 5 or 20 mmol
      L(-1) glucose and then treated with ABE. Streptozotocin-induced diabetic rats
      received 0, 10, or 40 mg kg(-1) ABE orally. Blood chemistry and phosphorylation
      of AMPK and Akt (a serine/threonine kinase) in the livers were examined. There
      was a significant increase in the levels of AMPK and Akt phosphorylation in ABE
      treated HepG2 cells. AMPK phosphorylation increased significantly in glucose
      stimulated HepG2 cells that were treated with ABE. In the 40 mg kg(-1) ABE
      treated diabetic rats, the glucose levels were lower than in the control.
      Phosphorylation of AMPK in ABE-untreated diabetic rat livers decreased
      significantly. Conversely, ABE treatment increased the phosphorylation of AMPK
      and Akt in the diabetic rat liver. CONCLUSION: ABE treatment upregulated AMPK
      phosphorylation in HepG2 cells, and upregulated AMPK and Akt phosphorylation in
      the diabetic rat liver. These data suggest that ABE can potentially improve
      glucose intolerance.

PMID- 26198389
TI  - Efficacy of rehabilitation (lengthening) exercises, platelet-rich plasma
      injections, and other conservative interventions in acute hamstring injuries: an
      updated systematic review and meta-analysis.
AB  - BACKGROUND: Our 2012 review on therapeutic interventions for acute hamstring
      injuries found a lack of high-quality studies. The publication of new studies
      warranted an update. OBJECTIVES: To update and reanalyse the efficacy of
      conservative treatments for hamstring injury. DATA SOURCES: PubMed, EMBASE, Web
      of Science, Cochrane library, CINAHL and SPORTDiscus were searched till mid
      February 2015. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) on
      the effect of conservative interventions versus a control group or other
      intervention for hamstring injuries (HI) were included. DATA ANALYSIS: The search
      results were screened independently by two authors. Risk of bias assessment was
      performed using a modified Downs and Black scale with a maximum score of 28. Meta
      analysis was performed, where possible. MAIN RESULTS: 10 RCTs (526 participants),
      including 6 new RCTs, were identified. Two RCTs were of good/excellent quality,
      the rest were fair or poor (median Downs and Black score 16 (IQR 9)). Meta
      analysis of two studies on rehabilitation (lengthening) exercises showed a
      significantly reduced time to return to play (HR 3.22 (95% CI 2.17 to 4.77),
      p<0.0001) but no difference in risk of re-injury. Meta-analysis of three studies
      investigating platelet-rich plasma (PRP) showed no effect when compared to
      control (HR 1.03 (95% CI 0.87 to 1.22), p=0.73). Limited evidence was found that
      progressive agility and trunk stability training may reduce re-injury rates.
      CONCLUSIONS: Meta-analysis showed superior efficacy for rehabilitation exercises.
      PRP injection had no effect on acute hamstring injury. Limited evidence was found
      that agility and trunk stabilisation may reduce re-injury rates. The limitations
      identified in the majority of RCTs should improve the design of new hamstring
      RCTs.

PMID- 26198390
TI  - COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain.
AB  - When measured once, psychological stress predicts development of painful
      temporomandibular disorder (TMD). However, a single measurement fails to
      characterize the dynamic nature of stress over time. Moreover, effects of stress
      on pain likely vary according to biological susceptibility. We hypothesized that
      temporal escalation in stress exacerbates risk for TMD, and the effect is
      amplified by allelic variants in a gene, catechol-O-methyltransferase (COMT),
      regulating catechol neurotransmitter catabolism. We used data from the Orofacial
      Pain: Prospective Evaluation and Risk Assessment prospective cohort study of
      2,707 community-dwelling adults with no lifetime history of TMD on enrollment. At
      baseline and quarterly periods thereafter, the Perceived Stress Scale (PSS)
      measured psychological stress. Genotyped DNA from blood samples determined COMT
      diplotypes. During follow-up of 0.25 to 5.2 y, 248 adults developed examiner
      verified incident TMD. PSS scores at baseline were 20% greater (P < 0.001) in
      adults who developed incident TMD compared with TMD-free controls. Baseline PSS
      scores increased by 9% (P = 0.003) during follow-up in cases but remained stable
      in controls. This stress escalation was limited to incident cases with COMT
      diplotypes coding for low-activity COMT, signifying impaired catabolism of
      catecholamines. Cox regression models confirmed significant effects on TMD hazard
      of both baseline PSS (P < 0.001), modeled as a time-constant covariate, and
      change in PSS (P < 0.001), modeled as a time-varying covariate. Furthermore, a
      significant (P = 0.04) interaction of COMT diplotype and time-varying stress
      showed that a postbaseline increase of 1.0 standard deviation in PSS more than
      doubled risk of TMD incidence in subjects with low-activity COMT diplotypes
      (hazard ratio = 2.35; 95% confidence limits: 1.66, 3.32), an effect not found in
      subjects with high-activity COMT diplotypes (hazard ratio = 1.42; 95% confidence
      limits: 0.96, 2.09). Findings provide novel insights into dynamic effects of
      psychological stress on TMD pain, highlighting that effects are most pronounced
      in individuals whose genetic susceptibility increases responsiveness to
      catecholamine neurotransmitters. 

PMID- 26198391
TI  - Association of Synergistetes and Cyclodipeptides with Periodontitis.
AB  - The purpose of this study was to evaluate the microbial community (MC)
      composition as it relates to salivary metabolites and periodontal clinical
      parameters in a 21-d biofilm-overgrowth model. Subjects (N = 168) were enrolled
      equally into 5 categories of periodontal status per the biofilm-gingival
      interface classification. Microbial species within subgingival plaque samples
      were identified by human microbiome identification microarray. Whole saliva was
      analyzed by liquid chromatography-mass spectrometry and gas chromatography-mass
      spectrometry for metabolite identification. Phylum was grouped into MCs according
      to principal component analysis. Generalized linear and regression models were
      used to examine the association among MC, species, periodontal clinical
      parameters, and salivary metabolome. Multiple comparisons were adjusted with the
      false discovery rate. The study population was distributed into 8 distinct MC
      profiles, designated MC-1 to MC-8. MC-2 explained 14% of the variance and was
      dominated by Synergistetes and Spirochaetes. It was the only community structure
      significantly associated with high probing depth (P = 0.02) and high bleeding on
      probing (P = 0.008). MC-2 was correlated with traditional periodontal pathogens
      and several newly identified putative periodontal pathogens: Fretibacterium
      fastidiosum, Fretibacterium sp. OT360/OT362, Filifactor alocis, Treponema
      lecithinolyticum, Eubacterium saphenum, Desulfobulbus sp./OT041, and
      Mogibacterium timidum. Synergistetes phylum was strongly associated with 2 novel
      metabolites-cyclo (-leu-pro) and cyclo (-phe-pro)-at 21 d of biofilm overgrowth
      (P = 0.02). In subjects with severe periodontitis (P2 and P3), cyclo (-leu-pro)
      and cyclo (-phe-pro) were significantly associated with increased changes in
      probing depth at 21 d of biofilm overgrowth (P <= 0.05). The analysis identified
      a MC dominated by Synergistetes, with classic and putative newly identified
      pathogens/pathobionts associated with clinical disease. The metabolomic discovery
      of 2 novel cyclodipeptides that have been reported to serve as quorum-sensing
      and/or bacteriocidal/bacteriostatic molecules, in association with Synergistetes,
      suggests a potential role in periodontal biofilm dysbiosis and periodontal
      disease that warrants further investigation. 

PMID- 26198392
TI  - EFFECTIVENESS OF DIAPERS AMONG PEOPLE WITH CHRONIC INCONTINENCE IN THAILAND.
AB  - OBJECTIVES: The aim of this study was to assess effect of adult diapers on health
      related quality of life (HRQOL) and the independent level of performing
      activities of daily living (ADLs) in people with urinary or fecal incontinence.
      Psychological consequences of patients' caregivers were also measured. METHODS:
      This quasi-experimental study was conducted at two rehabilitation centers in
      Thailand. People aged 15 years or greater with chronic urinary or fecal
      incontinence were eligible. Study participants received adult diapers for 10
      weeks after recruitment. Thai EuroQol Five Dimensions (EQ-5D) and the Barthel
      Index were measured at baseline and weeks 2, 6, and 10 to evaluate HRQOL and the
      independent level of performing ADLs, respectively. The Braden Scale was used to
      assess the risk of having pressure ulcers. Mean differences in the Thai EQ-5D,
      the Barthel Index, and the Braden Scale, before and after receiving adult
      diapers, were estimated using a multilevel linear regression model. RESULTS:
      There were ninety patients and forty-eight caregivers who took part in this
      study. HRQOL and independent level of performing ADLs had improved significantly
      by week 10 after receiving adult diapers with mean differences of 0.102 (95%
      confidence interval [CI], 0.046-0.158) and 4.40 (95% CI, 1.74-7.07),
      respectively. The risk of having pressure ulcers had significantly decreased by
      67 percent (95% CI, 16 percent-78 percent) by week 10 after receiving adult
      diapers. CONCLUSIONS: The results indicate a significant improvement of HRQOL and
      the independent level of performing ADLs among incontinent patients after
      receiving adult diapers. These results were used to inform the development of the
      health benefits package under the Universal Health Coverage Scheme in Thailand.

PMID- 26198394
TI  - Effect of reducing the nicotine content of cigarettes on cigarette smoking
      behavior and tobacco smoke toxicant exposure: 2-year follow up.
AB  - BACKGROUND AND AIMS: A broadly mandated reduction of the nicotine content (RNC)
      of cigarettes has been proposed in the United States to reduce the addictiveness
      of cigarettes, to prevent new smokers from becoming addicted and to facilitate
      quitting in established smokers. The primary aim of this study was to determine
      whether following 7 months of smoking very low nicotine content cigarettes
      (VLNC), and then returning to their own cigarettes, smokers would demonstrate
      persistently reduced nicotine intake compared with baseline or quit smoking.
      METHODS: In a community-based clinic 135 smokers not interested in quitting were
      randomized to one of two groups. A research group smoked their usual brand of
      cigarettes, followed by five types of research cigarettes with progressively
      lower nicotine content, each for 1 month, followed by 6 months at the lowest
      nicotine level (0.5 mg/cigarette) (53 subjects) and then 12 months with no
      intervention (30 subjects completed). A control group smoked their usual brand
      for the same period of time (50 subjects at 6 months, 38 completed). Smoking
      behavior, biomarkers of nicotine intake and smoke toxicant exposure were
      measured. RESULTS: After 7 months smoking VLNC, nicotine intake remained below
      baseline (plasma cotinine 149 versus 250 ng/ml, P<0.005) with no significant
      change in cigarettes per day or expired carbon monoxide (CO). During the 12-month
      follow-up, cotinine levels in RNC smokers rose to baseline levels and to those of
      control smokers. Quit rates among RNC smokers were very low [7.5 versus 2% in
      controls, not significant). CONCLUSIONS: In smokers not interested in quitting,
      reducing the nicotine content in cigarettes over 12 months does not appear to
      result in extinction of nicotine dependence, assessed by persistently reduced
      nicotine intake or quitting smoking over the subsequent 12 months.

PMID- 26198395
TI  - Validation in the Absence of Observed Events.
AB  - This article addresses the problem of validating models in the absence of
      observed events, in the area of weapons of mass destruction terrorism risk
      assessment. We address that problem with a broadened definition of "validation,"
      based on stepping "up" a level to considering the reason why decisionmakers seek
      validation, and from that basis redefine validation as testing how well the model
      can advise decisionmakers in terrorism risk management decisions. We develop that
      into two conditions: validation must be based on cues available in the observable
      world; and it must focus on what can be done to affect that observable world,
      i.e., risk management. That leads to two foci: (1) the real-world risk generating
      process, and (2) best use of available data. Based on our experience with nine
      WMD terrorism risk assessment models, we then describe three best use of
      available data pitfalls: SME confidence bias, lack of SME cross-referencing, and
      problematic initiation rates. Those two foci and three pitfalls provide a basis
      from which we define validation in this context in terms of four tests--Does the
      model: ... capture initiation? ... capture the sequence of events by which attack
      scenarios unfold? ... consider unanticipated scenarios? ... consider alternative
      causal chains? Finally, we corroborate our approach against three validation
      tests from the DOD literature: Is the model a correct representation of the
      process to be simulated? To what degree are the model results comparable to the
      real world? Over what range of inputs are the model results useful?

PMID- 26198393
TI  - Genome-wide association study identifies variants at 16p13 associated with
      survival in multiple myeloma patients.
AB  - Here we perform the first genome-wide association study (GWAS) of multiple
      myeloma (MM) survival. In a meta-analysis of 306 MM patients treated at UCSF and
      239 patients treated at the Mayo clinic, we find a significant association
      between SNPs near the gene FOPNL on chromosome 16p13 and survival (rs72773978;
      P=6 * 10(-10)). Patients with the minor allele are at increased risk for
      mortality (HR: 2.65; 95% CI: 1.94-3.58) relative to patients homozygous for the
      major allele. We replicate the association in the IMMEnSE cohort including 772
      patients, and a University of Utah cohort including 318 patients (rs72773978
      P=0.044). Using publicly available data, we find that the minor allele was
      associated with increased expression of FOPNL and increased expression of FOPNL
      was associated with higher expression of centrosomal genes and with shorter
      survival. Polymorphisms at the FOPNL locus are associated with survival among MM
      patients. 

PMID- 26198400
TI  - Stress Testing After Percutaneous Coronary Intervention in the Veterans Affairs
      HealthCare System: Insights from the Veterans Affairs Clinical Assessment,
      Reporting, and Tracking Program.
AB  - BACKGROUND: Stress testing after percutaneous coronary intervention (PCI) in fee
      for-service settings is common and rates vary by hospital. Rates of stress
      testing after PCI within integrated healthcare systems, such as the Veterans
      Affairs (VA) are unknown. METHODS AND RESULTS: We evaluated all VA patients who
      underwent PCI from October 2007 through June 2010. To avoid the influence of
      Medicare eligibility on rates of stress testing use in the VA, we excluded
      Medicare eligible patients during the follow-up period. Hospital-level variation
      in risk-standardized rates of stress testing and the association with 1-year
      mortality and myocardial infarction was determined from Markov chain Monte Carlo
      methods. Among 10 293 patients undergoing PCI at 55 VA hospitals, 2239 (21.8%)
      had a stress test performed within 1 year of PCI and 3902 (37.9%) within 2 years.
      Most stress tests after PCI were performed with nuclear imaging (79.8%). The
      hospital-level risk-standardized rate of stress testing differed significantly
      from the average at 14 hospitals, with 8 (14.5%) hospitals significantly below
      and 6 (10.9%) hospitals significantly above the average stress testing rate.
      Hospital-level risk-standardized stress testing rates were not significantly
      correlated with risk-standardized mortality (Spearman rho=-0.24; P=0.08) or
      myocardial infarction rates (Spearman rho=0.20; P=0.14). CONCLUSIONS: In the VA,
      nearly 40% of patients underwent stress testing in the 2 years after PCI, which
      is a third less than published studies from other healthcare systems. However,
      stress testing rates varied across VA hospitals, suggesting opportunities to
      optimize the use of stress testing are still present in integrated healthcare
      systems.

PMID- 26198401
TI  - The Epidemiology of Exertional Headache in the General Population of Tehran,
      Iran.
AB  - OBJECTIVE: In this cross-sectional study, we investigated the prevalence and
      characteristics of primary exertional headache (EH) among the Iranian general
      population living in Tehran, the capital city of the country. BACKGROUND:
      Headache is the most common complaint and is listed in the top 10 most disabling
      conditions. Epidemiological researches on headache can demonstrate its actual
      burden. There are still limited data on EH, especially in Iran and the Middle
      East. METHODS: A Persian questionnaire was designed based on the International
      Headache Society (IHS) criteria of headache disorders (ICHD-II). Face-to-face
      interviews were performed by 5 trained medical interns on a sample size of 2300
      people. RESULTS: Data for a total number of 2076 subjects were enrolled for final
      analysis. The mean age of the subjects at the time of the study was 36.3 +/- 14.6
      years. The 1-year prevalence of EH was 7.3% (95% confidence interval [CI]: 6.2
      8.4%). The prevalence of EH was significantly higher in females compared to males
      (10.0% vs 5.4%, P < .001). The mean age of the subjects with EH was 32 +/- 12.1
      years. None of our EH patients received medical consult prior to the study.
      CONCLUSION: EH seems to be less prevalent among the Iranian population compared
      to previous studies.

PMID- 26198402
TI  - Structural modeling and molecular simulation analysis of HvAP2/EREBP from barley.
AB  - AP2/ERF transcription factors play a critical role in plant development and
      stress adaptation. This study reports the three-dimensional ab initio-based model
      of AP2/EREBP protein of barley and its interaction with DNA. Full-length coding
      sequence of HvAP2/EREBP gene isolated from two Indian barley cultivars, RD 2503
      and RD 31, was used to model the protein. Of five protein models obtained, the
      one with lowest C-score was chosen for further analysis. The N- and C-terminal
      regions of HvAP2 protein were found to be highly disordered. The dynamic
      properties of AP2/EREBP and its interaction with DNA were investigated by
      molecular dynamics simulation. Analysis of trajectories from simulation yielded
      the equilibrated conformation between 2-10ns for protein and 7-15ns for protein
      DNA complex. We established relationship between DNA having GCC box and DNA
      binding domain of HvAP2/EREBP was established by modeling 11-base-pair-long
      nucleotide sequence and HvAP2/EREBP protein using ab initio method. Analysis of
      protein-DNA interaction showed that a beta-sheet motif constituting amino acid
      residues THR105, ARG100, ARG93, and ARG83 seems to play important role in
      stabilizing the complex as they form strong hydrogen bond interactions with the
      DNA motif. Taken together, this study provides first-hand comprehensive
      information detailing structural conformation and interactions of HvAP2/EREBP
      proteins in barley. The study intensifies the role of computational approaches
      for preliminary examination of unknown proteins in the absence of experimental
      information. It also provides molecular insight into protein-DNA binding for
      understanding and enhancing abiotic stress resistance for improving the water use
      efficiency in crop plants. 

PMID- 26198403
TI  - Targeting helicase-dependent amplification products with an electrochemical
      genosensor for reliable and sensitive screening of genetically modified
      organisms.
AB  - Cultivation of genetically modified organisms (GMOs) and their use in food and
      feed is constantly expanding; thus, the question of informing consumers about
      their presence in food has proven of significant interest. The development of
      sensitive, rapid, robust, and reliable methods for the detection of GMOs is
      crucial for proper food labeling. In response, we have experimentally
      characterized the helicase-dependent isothermal amplification (HDA) and sequence
      specific detection of a transgene from the Cauliflower Mosaic Virus 35S Promoter
      (CaMV35S), inserted into most transgenic plants. HDA is one of the simplest
      approaches for DNA amplification, emulating the bacterial replication machinery,
      and resembling PCR but under isothermal conditions. However, it usually suffers
      from a lack of selectivity, which is due to the accumulation of spurious
      amplification products. To improve the selectivity of HDA, which makes the
      detection of amplification products more reliable, we have developed an
      electrochemical platform targeting the central sequence of HDA copies of the
      transgene. A binary monolayer architecture is built onto a thin gold film where,
      upon the formation of perfect nucleic acid duplexes with the amplification
      products, these are enzyme-labeled and electrochemically transduced. The
      resulting combined system increases genosensor detectability up to 10(6)-fold,
      allowing Yes/No detection of GMOs with a limit of detection of ~30 copies of the
      CaMV35S genomic DNA. A set of general utility rules in the design of genosensors
      for detection of HDA amplicons, which may assist in the development of point-of
      care tests, is also included. The method provides a versatile tool for detecting
      nucleic acids with extremely low abundance not only for food safety control but
      also in the diagnostics and environmental control areas. 

PMID- 26198404
TI  - Detection of prostate cancer index lesions with multiparametric magnetic
      resonance imaging (mp-MRI) using whole-mount histological sections as the
      reference standard.
AB  - OBJECTIVE: To evaluate the sensitivity of multiparametric magnetic resonance
      imaging (mp-MRI) for detecting prostate cancer foci, including the largest
      (index) lesions. PATIENTS AND METHODS: In all, 115 patients with biopsy confirmed
      prostate cancer underwent mp-MRI before radical prostatectomy. A single expert
      radiologist recorded all prostate cancer foci including the index lesion
      'blinded' to the pathologist's biopsy report. Stained whole-mount histological
      sections were used as the reference standard. All lesions were contoured by an
      experienced uropathologist who assessed their volume and pathological Gleason
      score. All lesions with a volume of >0.5 mL and/or pathological Gleason score of
      >6 were defined as clinically significant prostate cancer. Multivariate analysis
      was used to ascertain the characteristics of lesions identified by MRI. RESULTS:
      In all, 104 of 115 index lesions were correctly diagnosed by mp-MRI (sensitivity
      90.4%; 95% confidence interval [CI] 83.5-95.1%), including 98/105 clinically
      significant index lesions (93.3%; 95% CI 86.8-97.3%), among which three of three
      lesions had a volume of <0.5 mL and Gleason score of >6. Overall, mp-MRI detected
      131/206 lesions including 13 of 68 'insignificant' prostate cancers. The
      multivariate logistic regression modelling showed that pathological Gleason score
      (odds ratio [OR] 11.7, 95% CI 2.3-59.8; P = 0.003) and lesion volume (OR 4.24,
      95% CI 1.3-14.7; P = 0.022) were independently associated with the detection of
      index lesions at MRI. CONCLUSIONS: This study shows that mp-MRI has a high
      sensitivity for detecting clinically significant prostate cancer index lesions,
      while having disappointing results for the detection of small-volume, low Gleason
      score prostate cancer foci. Thus, mp-MRI could be used to stratify patients
      according to risk, allowing better treatment selection.

PMID- 26198407
TI  - Do adolescents who are night owls have a higher risk of dental caries? - a case
      control study.
AB  - OBJECTIVE: The aim was to evaluate the association between circadian rhythm and
      the risk of caries in adolescents, as well as their dietary and toothbrushing
      habits. METHODS: A group of 196 adolescents (15 and 16 years old) were divided
      into two equal groups based on caries risk (case = high risk; and control = low
      risk). Before their dental examinations, they were asked to complete a
      questionnaire. The questionnaire included questions on circadian rhythm, dietary
      and oral self-care habits, and demographic variables. The participants were
      divided into three circadian types: evening types who are alert in the evening
      and tired in the morning; morning types who are the opposite; and neutral types
      who are neither particularly alert in the evening nor extremely tired in the
      morning. RESULTS: The most common sleep-cycle group type was neutral (50%). After
      this came evening types (37%) and finally morning types (13%). Morning and
      neutral types reported more frequently than evening types that they had breakfast
      every morning and brushed their teeth twice a day. More evening types were
      categorized as at high risk of caries. Circadian rhythm, breakfast habits and
      toothbrushing frequency were associated with a high risk of caries. The predicted
      probability of being at high risk of caries was almost four times higher for
      evening types than for morning types (OR 3.8; 95% CI 1.3-10.9). CONCLUSION:
      Adolescents who belonged to the evening circadian rhythm group brushed their
      teeth more seldom, ate breakfast less regularly and had a higher risk of caries
      than morning types. A patient's circadian rhythm should be considered when
      planning oral health education for adolescents with a high risk of caries.

PMID- 26198406
TI  - Generation of lentivirus-induced dendritic cells under GMP-compliant conditions
      for adaptive immune reconstitution against cytomegalovirus after stem cell
      transplantation.
AB  - BACKGROUND: Reactivation of latent viruses such as human cytomegalovirus (HCMV)
      after allogeneic hematopoietic stem cell transplantation (HSCT) results in high
      morbidity and mortality. Effective immunization against HCMV shortly after allo
      HSCT is an unmet clinical need due to delayed adaptive T cell development. Donor
      derived dendritic cells (DCs) have a critical participation in stimulation of
      naive T cells and immune reconstitution, and therefore adoptive DC therapy could
      be used to protect patients after HSCT. However, previous methods for ex vivo
      generation of adoptive donor-derived DCs were complex and inconsistent,
      particularly regarding cell viability and potency after thawing. We have
      previously demonstrated in humanized mouse models of HSCT the proof-of-concept of
      a novel modality of lentivirus-induced DCs ("SmyleDCpp65") that accelerated
      antigen-specific T cell development. METHODS: Here we demonstrate the feasibility
      of good manufacturing practices (GMP) for production of donor-derived DCs
      consisting of monocytes from peripheral blood transduced with an integrase
      defective lentiviral vector (IDLV, co-expressing GM-CSF, IFN-alpha and the
      cytomegalovirus antigen pp65) that were cryopreserved and thawed. RESULTS:
      Upscaling and standardized production of one lot of IDLV and three lots of
      SmyleDCpp65 under GMP-compliant conditions were feasible. Analytical parameters
      for quality control of SmyleDCpp65 identity after thawing and potency after
      culture were defined. Cell recovery, uniformity, efficacy of gene transfer,
      purity and viability were high and consistent. SmyleDCpp65 showed only residual
      and polyclonal IDLV integration, unbiased to proto-oncogenic hot-spots.
      Stimulation of autologous T cells by GMP-grade SmyleDCpp65 was validated.
      CONCLUSION: These results underscore further developments of this individualized
      donor-derived cell vaccine to accelerate immune reconstitution against HCMV after
      HSCT in clinical trials.

PMID- 26198408
TI  - Full-length sequence of KIR3DL1*0310102 detected in DNA samples from West Africa.
AB  - KIR3DL1*0310102 differs from KIR3DL1*0150101 with 11 nucleotide substitutions. 

PMID- 26198410
TI  - Specialised emission pattern of leaf trace in a late Permian (253 million-years
      old) conifer.
AB  - Leaf traces are important structures in higher plants that connect leaves and the
      stem vascular system. The anatomy and emission pattern of leaf traces are well
      studied in extant vascular plants, but remain poorly understood in fossil
      lineages. We quantitatively analysed the leaf traces in the late Permian conifer
      Ningxiaites specialis from Northwest China based on serial sections through pith,
      primary and secondary xylems. A complete leaf traces emission pattern of a
      conifer is presented for the first time from the late Palaeozoic. Three to five
      monarch leaf traces are grouped in clusters, arranged in a helical phyllotaxis.
      The leaf traces in each cluster can be divided into upper, middle and lower
      portions, and initiate at the pith periphery and cross the wood horizontally. The
      upper leaf trace increases its diameter during the first growth increment and
      then diminishes completely, which indicates leaf abscission at the end of the
      first year. The middle trace immediately bifurcates once or twice to form two or
      three vascular bundles. The lower trace persists as a single bundle during its
      entire length. The intricate leaf trace dynamics indicates this fossil plant had
      a novel evolutionary habit by promoting photosynthetic capability for the matured
      plant. 

PMID- 26198409
TI  - Expression of dsRNA in recombinant Isaria fumosorosea strain targets the TLR7
      gene in Bemisia tabaci.
AB  - BACKGROUND: RNA interference (RNAi) technology shows a great potential in
      controlling agricultural pests, despite the difficulty of introducing exogenous
      dsRNA/siRNA into target pests. Isaria fumosorosea is a common fungal pathogen of
      the B-biotype Bemisia tabaci (whitefly), which is a widespread pest.
      Entomopathogenic fungi directly penetrate the cuticle and invade insect hemocoel.
      Application of I. fumosorosea expressing dsRNA of whitefly immunity-related gene
      may aid in developing RNAi technology to effectively control whiteflies. METHODS:
      A dsRNA expression plasmid, psTLR7, was constructed by introducing the Toll-like
      receptor 7 (TLR7) gene of B-biotype whitefly to the silent vector, pSilent-1. The
      plasmid psTLR7 was transferred into the protoplast of the I. fumosorosea strain
      IfB01. Then, the recombinant strain was screened out based on the biological
      stability and bioactivity against whitefly. RESULTS: A genetically stable
      recombinant strain IfB01-TRL7 was screened out. The impact of IfB01-TRL7 against
      whitefly TRL7 gene was validated by qPCR. Lower expression levels of the TLR7
      gene was observed in the whiteflies infected by the recombinant strain. The
      bioassay results indicated that compared to IfB01 strain, IfB01-TRL7 increased
      the mortality of whitefly nymphs, and decreased and shortened the values of LC50
      and LT50, thus indicating higher virulence of IfB01-TRL7. CONCLUSION: The
      expression of the dsRNA of whitefly TLR7 gene in recombinant I. fumosorosea
      strain successfully knocked down the host target gene by infecting the nymphs and
      enhanced the whiteflies mortality. The present study will give insight to new
      application of RNAi technology for more effective biocontrol of this pests.

PMID- 26198411
TI  - Polarized emission from stretched PPV films viewed at the molecular level.
AB  - We present a study on the photoluminescence (PL) of thin films of poly-(p
      phenylene vinylene) (PPV), non-stretched and uniaxially stretched. The
      experimental study was carried out using linear polarized light as the excitation
      beam, oriented either parallel or perpendicular to the stretch axis (S). The
      results showed that when the excitation light source has polarization
      perpendicularly oriented to the stretch direction, the emitted PL presents
      maximum intensity in the orientation S, and a minimum in the direction orthogonal
      to S. In order to understand this interesting phenomenon, we employ theoretical
      simulations at the atomistic level. We use classical molecular dynamics to
      simulate amorphous PPV films, non-stretched and stretched, from which we find a
      tendency of overall alignment of PV units to S, and of local clustering in
      herring-bone and pi-stacking partial symmetries. Our study of optical activity of
      these kinds of clusters, performed through a quantum semi-empirical method,
      allows us to explain this polarization conversion behavior, and indicates the
      possibility of using underivatized PPV as the active layer for polarized
      electroluminescent devices. 

PMID- 26198412
TI  - Tolerance of an Antarctic Bacterium to Multiple Environmental Stressors.
AB  - A population of cold-tolerant Antarctic bacteria was screened for their ability
      to tolerate other environmental stress factors. Besides low temperature, they
      were predominantly found to be tolerant to alkali. Attempt was also made to
      postulate a genetic basis of their multistress-tolerance. Transposon mutagenesis
      of an isolate Pseudomonas syringae Lz4W was performed, and mutants with delayed
      growth at low temperature were further screened for sensitivity to some other
      stress factors. A number of multistress-sensitive mutants were isolated. The
      mutated gene in one of the mutants sensitive to low temperature, acid and alkali
      was found to encode citrate synthase. Possible role of citrate synthase in
      conferring multistress-tolerance was postulated. 

PMID- 26198413
TI  - Characterization of Escherichia coli Isolates from an Urban Lake Receiving Water
      from a Wastewater Treatment Plant in Mexico City: Fecal Pollution and Antibiotic
      Resistance.
AB  - The presence of enteric bacteria in water bodies is a cause of public health
      concerns, either by directly causing water- and food-borne diseases, or acting as
      reservoirs for antibiotic resistance determinants. Water is used for crop
      irrigation; and sediments and aquatic plants are used as fertilizing supplements
      and soil conditioners. In this work, the bacterial load of several micro
      environments of the urban lake of Xochimilco, in Mexico City, was characterized.
      We found a differential distribution of enteric bacteria between the water
      column, sediment, and the rhizoplane of aquatic plants, with human fecal bacteria
      concentrating in the sediment, pointing to the need to assess such bacterial load
      for each micro-environment, for regulatory agricultural purposes, instead of only
      the one of the water, as is currently done. Resistance to tetracycline,
      ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole was common among
      Escherichia coli isolates, but was also differentially distributed, being again
      higher in sediment isolates. A distinct distribution of chloramphenicol minimum
      inhibitory concentrations (MIC) among these isolates suggests the presence of a
      local selective pressure favoring lower MICs than those of isolates from treated
      water. Fecal bacteria of human origin, living in water bodies along with their
      antibiotic resistance genes, could be much more common than typically considered,
      and pose a higher health risk, if assessments are only made on the water column
      of such bodies.

PMID- 26198414
TI  - Characterization of carbapenem-resistant Gram-negative bacteria from Tamil Nadu.
AB  - Carbapenem resistance is disseminating worldwide among Gram-negative bacteria.
      The aim of this study was to identify carbapenem-resistance level and to
      determine the mechanism of carbapenem resistance among clinical isolates from two
      centres in Tamil Nadu. In the present study, a total of 93 Gram-negative
      isolates, which is found to be resistant to carbapenem by disk diffusion test in
      two centres, were included. All isolates are identified at species level by 16S
      rRNA sequencing. Minimal inhibitory concentrations (MICs) of isolates for
      Meropenem were tested by agar dilution method. Presence of blaOXA, blaNDM,
      blaVIM, blaIMP and blaKPC genes was tested by PCR in all isolates. Amplicons were
      sequenced for confirmation of the genes. Among 93 isolates, 48 (%52) were
      Escherichia coli, 10 (%11) Klebsiella pneumoniae, nine (%10) Pseudomonas
      aeruginosa. Minimal inhibitory concentration results showed that of 93 suspected
      carbapenem-resistant isolates, 27 had meropenem MICs >= 2 MUg/ml. The MIC range,
      MIC50 and MIC90 were < 0.06 to >128 MUg/ml, 0.12 and 16 MUg/ml, respectively.
      Fig. 1 . Among meropenem-resistant isolates, E. coli were the most common (9/48,
      22%), followed by K. pneumoniae (7/9, 77%), P. aeruginosa (6/10, 60%),
      Acinetobacter baumannii (2/2, 100%), Enterobacter hormaechei (2/3, 67%) and one
      Providencia rettgeri (1/1, 100%). PCR results showed that 16 of 93 carried
      blaNDM, three oxa181, and one imp4. Among blaNDM carriers, nine were E. coli,
      four Klebsiella pneumoniae, two E. hormaechei and one P. rettgeri. Three K.
      pneumoniae were OXA-181 carriers. The only imp4 carrier was P. aeruginosa. A
      total of seven carbapenem-resistant isolates were negatives by PCR for the genes
      studied. All carbapenem-resistance gene-positive isolates had meropenem MICs >2
      MUg/ml. Our results confirm the dissemination of NDM and emergence of OXA-181
      beta-lactamase among Gram-negative bacteria in South India. This study showed the
      emergence of NDM producer in clinical isolates of E. hormaechei and P. rettgeri
      in India. 

PMID- 26198415
TI  - Dual Drug Delivery Using Lactic Acid Conjugated SLN for Effective Management of
      Neurocysticercosis.
AB  - PURPOSE: The debut study was aimed to develop Lactic acid (LA)-conjugated solid
      lipid nanoparticles (SLN-LA) bearing albendazole (ALB) and prednisolone (PRD) for
      effective management of neurocysticercosis (NCC). METHODS: LA was coupled to SLN
      by post-insertion technique. SLNs were characterized for particle size and size
      distribution, shape, and percent drug entrapment efficiency. In vitro drug
      release kinetics, fluorescence study and in vitro transendothelial transport,
      hematological studies and pharmacokinetic studies were carried out to predict the
      fullest drug delivery potential. RESULTS: Spherical SLNs (~100 nm) with good drug
      entrapments (~64 and ~78% for ALB and PRD, respectively) showed in vitro initial
      fast release (i.e., 20-40% drugs release in 4 h) followed by sustained release
      for more than 48 h. Fluorescence study and in vitro transendothelial transport
      depicted selective brain uptake of SLN-LA compared to SLN attributed to carrier
      mediated transport via monocarboxylic acid transporters (MCT - 1/2/3).
      Pharmacokinetic parameters such as AUC0-t and AUMC0-t and Cllast showed good
      drugs withholding capacity of SLNs. Organ distribution studies reflected high
      accumulation of drugs (ALB, 7.6 +/- 0.31%; PRD, 5.21 +/- 0.24%) in the brain
      after 24 h in case of SLN-LA as compared to plain drugs solution. SLN-LA in
      hematological studies revealed insignificant toxicity to blood cells.
      CONCLUSIONS: The overall study paved the potential advances in brain targeting
      with synergistic acting drugs for effective management of NCC.

PMID- 26198416
TI  - Flower-like Palladium Nanoclusters Decorated Graphene Electrodes for
      Ultrasensitive and Flexible Hydrogen Gas Sensing.
AB  - Flower-like palladium nanoclusters (FPNCs) are electrodeposited onto graphene
      electrode that are prepared by chemical vapor deposition (CVD). The CVD graphene
      layer is transferred onto a poly(ethylene naphthalate) (PEN) film to provide a
      mechanical stability and flexibility. The surface of the CVD graphene is
      functionalized with diaminonaphthalene (DAN) to form flower shapes. Palladium
      nanoparticles act as templates to mediate the formation of FPNCs, which increase
      in size with reaction time. The population of FPNCs can be controlled by
      adjusting the DAN concentration as functionalization solution. These FPNCs_CG
      electrodes are sensitive to hydrogen gas at room temperature. The sensitivity and
      response time as a function of the FPNCs population are investigated, resulted in
      improved performance with increasing population. Furthermore, the minimum
      detectable level (MDL) of hydrogen is 0.1 ppm, which is at least 2 orders of
      magnitude lower than that of chemical sensors based on other Pd-based hybrid
      materials.

PMID- 26198417
TI  - Geochemical fractions of rare earth elements in soil around a mine tailing in
      Baotou, China.
AB  - Rare earth mine tailing dumps are environmental hazards because tailing easily
      leaches and erodes by water and wind. To assess the influence of mine tailing on
      the geochemical behavior of rare earth elements (REEs) in soil, sixty-seven
      surface soil samples and three soil profile samples were collected from different
      locations near China's largest rare earth mine tailing. The total concentration
      of REEs in surface soils ranged from 156 to 5.65 * 10(4) mg.kg(-1) with an
      average value of 4.67 * 10(3) mg.kg(-1), which was significantly higher than the
      average value in China (181 mg.kg(-1)). We found obvious fractionation of both
      light and heavy REEs, which was supported by the North American Shale Composite
      (NASC) and the Post-Archean Average Australian Shale (PAAS) normalized
      concentration ratios calculated for selected elements (La(N)/Yb(N), La(N)/Sm(N)
      and Gd(N)/Yb(N)). A slightly positive Ce anomaly and a negative Eu anomaly were
      also found. For all 14 REEs in soils, enrichment was intensified by the mine
      tailing sources and influenced by the prevailing wind.

PMID- 26198418
TI  - On the possibility of producing true real-time retinal cross-sectional images
      using a graphics processing unit enhanced master-slave optical coherence
      tomography system.
AB  - In a previous report, we demonstrated master-slave optical coherence tomography
      (MS-OCT), an OCT method that does not need resampling of data and can be used to
      deliver en face images from several depths simultaneously. In a separate report,
      we have also demonstrated MS-OCT's capability of producing cross-sectional images
      of a quality similar to those provided by the traditional Fourier domain (FD) OCT
      technique, but at a much slower rate. Here, we demonstrate that by taking
      advantage of the parallel processing capabilities offered by the MS-OCT method,
      cross-sectional OCT images of the human retina can be produced in real time. We
      analyze the conditions that ensure a true real-time B-scan imaging operation and
      demonstrate in vivo real-time images from human fovea and the optic nerve, with
      resolution and sensitivity comparable to those produced using the traditional FD
      based method, however, without the need of data resampling.

PMID- 26198419
TI  - Frequency-domain photothermoacoustic and ultrasonic imaging of blood and opto
      thermal effects of plasmonic nanoparticle concentrations.
AB  - We describe the use of combined ultrasonic imaging (USI) and photoacoustic radar
      imaging (PARI) with linear chirp laser modulation to provide visualization of
      blood with and without the use of gold nanoparticles. A blood vessel simulating
      sample (S1) containing pure sheep blood was shown to be an optically weak
      absorbing medium which satisfies thermal but not acoustic confinement. On the
      contrary, the blood-gold combinations (S2) using 10% and S3 (20%) Au
      concentrations behaved as optically strongly absorbing media. A heating
      efficiency of 0.54 to 8.60*10(3)   K cm(2) (-1) was determined for Au NPs. The
      optimal optical power modulation spectral density was determined to be in the
      range of 0.5 to 0.8 MHz and 0.3 to 1.0 MHz for USI and PARI, respectively. USI
      produced a better structural image while PARI produced a better functional image
      of the simulated blood vessel in the order of S2>S3>S1 due to enhanced signal-to
      noise ratio. Two-dimensional images of the simulated blood vessel were also
      obtained. In summary, the PA signal does not increase linearly with Au NP
      concentration and the change of blood osmolarity due to temperature increase can
      cause thermo-hemolysis of red blood cells which in turn degrades the PA signal
      and thus the blood imaging quality. On the other hand, USI produced the best
      structural image, S4, due to the strong US reflection response from Au NPs and
      its insensitivity to the presence of blood.

PMID- 26198420
TI  - Dominant oceanic bacteria secure phosphate using a large extracellular buffer.
AB  - The ubiquitous SAR11 and Prochlorococcus bacteria manage to maintain a sufficient
      supply of phosphate in phosphate-poor surface waters of the North Atlantic
      subtropical gyre. Furthermore, it seems that their phosphate uptake may counter
      intuitively be lower in more productive tropical waters, as if their cellular
      demand for phosphate decreases there. By flow sorting (33)P-phosphate-pulsed
      (32)P-phosphate-chased cells, we demonstrate that both Prochlorococcus and SAR11
      cells exploit an extracellular buffer of labile phosphate up to 5-40 times larger
      than the amount of phosphate required to replicate their chromosomes.
      Mathematical modelling is shown to support this conclusion. The fuller the buffer
      the slower the cellular uptake of phosphate, to the point that in phosphate
      replete tropical waters, cells can saturate their buffer and their phosphate
      uptake becomes marginal. Hence, buffer stocking is a generic, growth-securing
      adaptation for SAR11 and Prochlorococcus bacteria, which lack internal reserves
      to reduce their dependency on bioavailable ambient phosphate. 

PMID- 26198421
TI  - Patient- and treatment-specific predictors of genitourinary function after high
      dose-rate monotherapy for favorable prostate cancer.
AB  - PURPOSE: High-dose-rate (HDR) brachytherapy alone is an effective treatment
      option for patients with early-stage prostate cancer. The purpose of this study
      was to quantify patient-reported short- and long-term toxicity and quality of
      life (QOL) after HDR monotherapy. METHODS AND MATERIALS: Thirty-nine consecutive
      men between May 2001 and January 2012 were identified for this analysis. All
      patients underwent definitive HDR monotherapy for favorable prostate cancer to a
      total dose of 3150 cGy in three fractions, 3800 cGy in four fractions, or 3850 in
      five fractions. Patient-reported genitourinary function was assessed before HDR,
      during an acute period after treatment (within 90 days of HDR), and on long-term
      followup using the American Urological Association International Prostate Symptom
      Score, a urinary QOL Likert questionnaire, and the Sexual Health Inventory for
      Men questionnaire. Regression analyses were performed using the ordinary least
      squares method. RESULTS: With median followup of 57 months, biochemical
      progression-free survival was 100%. There were no grade >=3 toxicities. Dose to
      the urethra and bladder, as well as prostate size and intraprostatic urethra
      length were predictive for short-term changes in QOL. Advanced patient age was
      predictive for worse sexual function on both acute and long-term followup.
      CONCLUSIONS: Toxicity after HDR monotherapy for prostate cancer is acceptable.
      Patients with larger prostates, longer intraprostatic urethras, and greater doses
      to the bladder and urethra may experience worse acute urinary QOL. Older patients
      may experience greater impairment in sexual function in the short and long terms.

PMID- 26198422
TI  - Non-stenotic intracranial arteries have atherosclerotic changes in acute ischemic
      stroke patients: a 3T MRI study.
AB  - INTRODUCTION: The aim of this study is to evaluate the degree of atherosclerotic
      changes in intracranial arteries by assessing arterial wall thickness using T1
      weighted 3D-turbo spin echo (3D-TSE) and time-of-flight MR angiography (TOF-MRA)
      in patients with acute ischemic stroke as compared with unaffected controls.
      METHODS: Thirty-three patients with acute ischemic stroke and 36 control patients
      were analyzed. Acute ischemic stroke patients were divided according to TOAST
      classification. At both distal internal carotid arteries and basilar artery
      without stenosis, TOF-MRA was used to select non-stenotic portion of assessed
      arteries. 3D-TSE was used to measure the area including the lumen and wall
      (AreaOuter) and luminal area (AreaInner). The area of the vessel wall (AreaVW) of
      assessed intracranial arteries and the ratio index (RI) of each patient were
      determined. RESULTS: AreaInner, AreaOuter, AreaVW, and RI showed good inter
      observer reliability and excellent intra-observer reliability. AreaInner did not
      significantly differ between stroke patients and controls (P = 0.619). However,
      AreaOuter, AreaVW, and RI were significantly larger in stroke patients (P <
      0.001). The correlation coefficient between AreaInner and AreaOuter was higher in
      the controls (r = 0.918) than in large vessel disease patients (r = 0.778). RI of
      large vessel disease patients was significantly higher than that of normal
      control, small vessel disease, and cardioembolic groups. CONCLUSION: In patients
      with acute ischemic stroke, wall thickening and positive remodeling are evident
      in non-stenotic intracranial arteries. This change is more definite in stroke
      subtype that is related to atherosclerosis than that in other subtypes which are
      not.

PMID- 26198423
TI  - Response to the letter to the editor by Kristensen MM, Helge JW and Dela F.

PMID- 26198424
TI  - Exercise Recommendations and Considerations for Persons With Spinal Cord Injury.

PMID- 26198425
TI  - Is the introduction of violence and injury observatories associated with a
      reduction of violence in adult populations? Rationale and protocol for a
      systematic review.
AB  - INTRODUCTION: The violence and injury observatories developed in Colombia and
      found throughout the Americas and Western Europe aim to maximise inter
      institutional cooperation, information-sharing, analysis and security policy
      development initiatives to enhance governance. The purpose of the violence and
      injury observatories is directed towards preventing crime and violence at the
      local and regional levels. To date, there has been no systematic review of the
      literature to present a succinct review of the evidence. We therefore sought to
      summarise the evidence from existing studies on the contribution of violence and
      injury observatories towards violence prevention. METHODS AND ANALYSIS: A number
      of databases will be searched, supplemented by the same keyword searches in the
      grey literature. Search terms will include studies published from 1 January 1990
      to 30 October 2014. Study quality will be assessed using a validated quality
      assessment tool. Two researchers will independently assess articles for study
      eligibility to reduce bias, minimise errors and enhance the reliability of
      findings. Disagreements will be resolved by consensus among three authors. This
      review protocol has been published in the PROSPERO International Prospective
      Register of systematic reviews, registration number 2014:CRD42014009818.
      DISSEMINATION: There is a paucity of evidence for the effectiveness of violence
      and injury observatories and their influence on violence in an adult population.
      We plan to address this gap in knowledge by way of a systematic review and meta
      analysis outlined in this abstract. We anticipate that the results could be used
      by researchers and policymakers to help inform them of the efficacy of violence
      and injury observatories and their broader role in contributing to violence
      prevention. TRIAL REGISTRATION NUMBER: CRD42014009818.

PMID- 26198426
TI  - Impact of cardiovascular comorbidities on COPD Assessment Test (CAT) and its
      responsiveness to pulmonary rehabilitation in patients with moderate to very
      severe COPD: protocol of the Chance study.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major cause of
      morbidity and mortality. Patients with COPD are characterised by a reduced health
      status, which can be easily assessed by the COPD Assessment Test (CAT). Previous
      studies show that health status can be worsened by the presence of comorbidities.
      However, the impact of cardiovascular comorbidities on health status as assessed
      with CAT is not sufficiently investigated. Therefore, the current study has the
      following objectives: (1) to study the clinical, (patho)physiological and
      psychosocial determinants of the CAT, and impact of previously established and/or
      newly diagnosed cardiovascular comorbidities on health status in tertiary care
      patients with COPD; (2) to assess the effects of pulmonary rehabilitation on CAT
      scores in patients with COPD; (3) to develop reference values for the CAT in
      Dutch elderly patients without COPD; and (4) to validate the CAT in a broad
      sample of Dutch patients with COPD. METHODS AND ANALYSIS: The COPD, Health status
      and Comorbidities (Chance) study is a monocentre study consisting of an
      observational cross-sectional part and a longitudinal part. Demographic and
      clinical characteristics will be assessed in primary care, secondary care and
      tertiary care patients with COPD, and in patients without COPD. To assess health
      status, the CAT, Clinical COPD Questionnaire (CCQ) and St George's Respiratory
      Questionnaire (SGRQ) will be used. The longitudinal part consists of a
      comprehensive pulmonary rehabilitation programme in 500 tertiary care patients.
      For the cross-sectional part of the study, 150 patients without COPD, 100 primary
      care patients and 100 secondary care patients will be assessed during a single
      home visit. ETHICS AND DISSEMINATION: The Medical Ethical Committee of the
      Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands (METC
      11-3-070), has approved this study. The study has been registered at the Dutch
      Trial Register (NTR 3416).

PMID- 26198427
TI  - Access to healthcare and financial risk protection for older adults in Mexico:
      secondary data analysis of a national survey.
AB  - OBJECTIVES: While the benefits of Seguro Popular health insurance in Mexico
      relative to no insurance have been widely documented, little has been reported on
      its effects relative to the pre-existing Social Security health insurance. We
      analyse the effects of Social Security and Seguro Popular health insurances in
      Mexico on access to healthcare of older adults, and on financial risk protection
      to their households, compared with older adults without health insurance.
      SETTING: Secondary data analysis was performed using the 2012 Mexican Survey of
      Health and Nutrition (ENSANUT). PARTICIPANTS: The study population comprised
      18,847 older adults and 13,180 households that have an elderly member. OUTCOME
      MEASURES: The dependent variables were access to healthcare given the reported
      need, the financial burden imposed by health expenditures measured through
      catastrophic health-related expenditures, and using savings for health-related
      expenditures. Separate propensity score matching analyses were conducted for each
      comparison. The analysis for access was performed at the individual level, and
      the analysis for financial burden at the household level. In each case, matching
      on a wide set of relevant characteristics was achieved. RESULTS: Seguro Popular
      showed a protective effect against lack of access to healthcare for older adults
      compared with those with no insurance. The average treatment effect on the
      treated (ATET) was ascertained through using the nearest-neighbour matching (
      8.1%, t-stat -2.305) analysis. However, Seguro Popular did not show a protective
      effect against catastrophic expenditures in a household where an older adult
      lived. Social Security showed increased access to healthcare (ATET -11.3%, t-stat
      -3.138), and protective effect against catastrophic expenditures for households
      with an elderly member (ATET -1.9%, t-stat -2.178). CONCLUSIONS: Seguro Popular
      increased access to healthcare for Mexican older adults. Social Security showed a
      significant protective effect against lack of access and catastrophic
      expenditures compared with those without health insurance.

PMID- 26198428
TI  - A mixed methods study of the factors that influence whether intervention research
      has policy and practice impacts: perceptions of Australian researchers.
AB  - OBJECTIVES: To investigate researchers' perceptions about the factors that
      influenced the policy and practice impacts (or lack of impact) of one of their
      own funded intervention research studies. DESIGN: Mixed method, cross-sectional
      study. SETTING: Intervention research conducted in Australia and funded by
      Australia's National Health and Medical Research Council between 2003 and 2007.
      PARTICIPANTS: The chief investigators from 50 funded intervention research
      studies were interviewed to determine if their study had achieved policy and
      practice impacts, how and why these impacts had (or had not) occurred and the
      approach to dissemination they had employed. RESULTS: We found that statistically
      significant intervention effects and publication of results influenced whether
      there were policy and practice impacts, along with factors related to the nature
      of the intervention itself, the researchers' experience and connections, their
      dissemination and translation efforts, and the postresearch context. CONCLUSIONS:
      This study indicates that sophisticated approaches to intervention development,
      dissemination actions and translational efforts are actually widespread among
      experienced researches, and can achieve policy and practice impacts. However, it
      was the links between the intervention results, further dissemination actions by
      researchers and a variety of postresearch contextual factors that ultimately
      determined whether a study had policy and practice impacts. Given the complicated
      interplay between the various factors, there appears to be no simple formula for
      determining which intervention studies should be funded in order to achieve
      optimal policy and practice impacts.

PMID- 26198429
TI  - Genetic characterisation of microsporidia infecting Indian tasar silkworm,
      Antheraea mylitta, using morphology and molecular tools.
AB  - The utility of inter simple sequence repeat-PCR (ISSR-PCR) assay in the genetic
      characterisation and elucidation of the phylogenetic relationship of different
      microsporidian isolates infecting tropical tasar silkworm, Antheraea mylitta
      Drury, is demonstrated. A total of 22 different microsporidians collected from
      the diseased tasar silkworms from Jharkhand state of India were analysed using
      morphological characters and ISSR-PCR. Observations spores under phase contrast
      microscope revealed oval to elongate in shape with length ranging from 3.8 MUm to
      5.1 MUm and width from 2.6 MUm to 3.3 MUm. All the microsporidian isolates except
      MIJ-1gC showed gonadal infection and transovarial transmission in infected tasar
      silkworms. Fourteen out of 20 ISSR primers tested generated reproducible profiles
      and yielded a total of 281 fragments, of which 273 were polymorphic (97%). The
      degree of banding pattern was used to evaluate genetic distances and for
      phylogenetic analysis. The results demonstrated that ISSR analysis may be a
      useful and efficient tool for taxonomical grouping and phylogenetic
      classification of different microsporidians in general. 

PMID- 26198430
TI  - TMEM140 is associated with the prognosis of glioma by promoting cell viability
      and invasion.
AB  - BACKGROUND: Gliomas are the most common types of primary brain tumors in the
      adult central nervous system. TMEM140 is identified as an amplified gene in the
      human gastric cancer genome. However, the function of TMEM140 in gliomas has not
      been thoroughly elucidated. The aim of the current study was to determine the
      clinical significance of TMEM140 expression in patients with gliomas and its
      effect on tumor cell malignant phenotypes. METHODS: Immunohistochemical analysis
      and real-time reverse transcription PCR were performed to detect the expression
      levels of TMEM140 in 70 glioma brain tissue samples. Next, the correlation
      between the TMEM140 expression levels and the clinical characteristics and
      outcomes of glioma patients was statistically analyzed. TMEM140 expression was
      inhibited in two glioma cell lines (i.e., U87 and U373) using a knockdown method
      with small interfering RNA. Cell Counting Kit-8 and Transwell assays were used to
      investigate TMEM140 function during cell proliferation, invasion, and migration,
      respectively. Using flow cytometry and Western blot analysis, we subsequently
      determined the cell cycle and apoptosis profile of the TMEM140-silenced cells.
      RESULTS: TMEM140 protein expression was significantly higher in gliomas than in
      normal brain tissues (p < 0.0001). TMEM140 overexpression was strongly correlated
      with tumor size, histologic grade, and overall survival time (P < 0.05). TMEM140
      decreased cell viability in vitro and dramatically decreased tumor volume in
      vivo. This phenomenon might be caused by G1 phase cell cycle arrest and cell
      apoptosis. TMEM140 silencing could suppress the viability, migration, and
      invasion of glioma cells. CONCLUSIONS: Our results suggest that TMEM140
      expression is a prognostic factor that might play an important role in the
      viability, migration, and invasion of glioma cells. This study highlights the
      importance of TMEM140 as a novel prognostic marker and as an attractive
      therapeutic target for gliomas.

PMID- 26198431
TI  - In vitro cultivation and cryopreservation of Babesia bigemina sporokinetes in
      hemocytes of Rhipicephalus microplus.
AB  - Cultures of tick hemocytes represent alternative cell lines for the isolation and
      cultivation of a variety of hemoparasites. The present study reports the
      development and evaluation of methods for the in vitro culture and maintenance of
      sporokinetes of Babesia bigemina in association with hemocytes of the tick
      Rhipicephalus microplus. Hemolymph, from engorged females infected with B.
      bigemina sporokinetes, was incubated at 28  degrees C in L15 culture medium
      supplemented with 40% fetal bovine serum. Adherence of hemocytes to flask
      surfaces and the development of B. bigemina sporokinetes commenced on the first
      day of cultivation. The protozoa demonstrated clear motility and the capacity to
      adhere to hemocyte membranes for up to 25 days, at which time the hemocytes began
      to show signs of degeneration. Examination of Giemsa stained hemocyte cultures,
      revealed the presence of pyriformis forms, as well as mature and immature
      sporokinetes with dark red nuclei, centralized or near the apical extremities.
      Sporokinetes harvested from culture supernatants were cryopreserved in liquid
      nitrogen. Inoculation of parasite-free hemocyte cultures with defrosted
      sporokinetes, demonstrated the viability and interaction of the protozoa with the
      hemocytes over 21 days. Cultured hemocytes of R. microplus hold potential for
      development as a tool in the study of host parasite interactions and as a
      substrate for the in vitro maintenance of B. bigemina sporokinetes.

PMID- 26198433
TI  - Effect evaluation of an interprofessional medication therapy management approach
      for multimorbid patients in primary care: a cluster-randomized controlled trial
      in community care (WestGem study protocol).
AB  - BACKGROUND: Pharmaceutical practice worldwide is developing towards patient care.
      Medication Review (MR) and Medication Therapy Management (MTM) are evolving as
      the most prominent services in pharmaceutical care and have a strong potential to
      provide a large benefit for patients and society. MTMs can only be performed in
      an interprofessional, collaborative setting. Several international studies have
      explored the effects of a MTM on the quality of therapy and costs. For Germany
      the data is still deficient. This study aims to provide data on the effects of an
      interprofessional MTM regarding quality of therapy, quality of life, costs and
      cost-effectiveness. METHOD/DESIGN: The study is designed as a cluster-randomized
      controlled trial in primary care, involving 12 outpatient clinics (clusters) and
      165 patients. Primary care units are allocated to interventions using a Stepped
      Wedge Design. All units are initially assigned to the control group. After a 6
      month observation period, general practitioners (GP) are randomly allocated to
      one of three groups and the interprofessional medication therapy management
      approach is implemented sequentially per each group with a lag of 3 months
      between. The primary outcome is the change in the quality of therapy measured by
      the MAI (Medication Appropriateness Index). Secondary outcomes include changes in
      the number of drug related problems, medication complexity, changes in drug
      adherence, changes in health-status and function, quality of life, direct costs
      and the incremental cost-effectiveness ratio. The acceptance of the
      interprofessional Medication Therapy Management approach is assessed by
      qualitative methods. DISCUSSION: The patient interview and brown bag review are
      activities, typically provided by the pharmacist. In this trial the patient is
      blinded to the pharmacist. The strength of having the patient blinded to the
      pharmacists is to exclude skepticism of the patient toward unknown pharmacies,
      which might be a major confounder in a regional and community setting. A weakness
      is that some patient related data might reach the pharmacists in a way, which
      might differ from self-acquired data. TRIAL REGISTRATION: Current controlled
      trials ISRCTN41595373 .

PMID- 26198432
TI  - Unearthing the genomes of plant-beneficial Pseudomonas model strains WCS358,
      WCS374 and WCS417.
AB  - BACKGROUND: Plant growth-promoting rhizobacteria (PGPR) can protect plants
      against pathogenic microbes through a diversity of mechanisms including
      competition for nutrients, production of antibiotics, and stimulation of the host
      immune system, a phenomenon called induced systemic resistance (ISR). In the past
      30 years, the Pseudomonas spp. PGPR strains WCS358, WCS374 and WCS417 of the
      Willie Commelin Scholten (WCS) collection have been studied in detail in
      pioneering papers on the molecular basis of PGPR-mediated ISR and mechanisms of
      biological control of soil-borne pathogens via siderophore-mediated competition
      for iron. RESULTS: The genomes of the model WCS PGPR strains were sequenced and
      analyzed to unearth genetic cues related to biological questions that surfaced
      during the past 30 years of functional studies on these plant-beneficial
      microbes. Whole genome comparisons revealed important novel insights into iron
      acquisition strategies with consequences for both bacterial ecology and plant
      protection, specifics of bacterial determinants involved in plant-PGPR
      recognition, and diversity of protein secretion systems involved in microbe
      microbe and microbe-plant communication. Furthermore, multi-locus sequence
      alignment and whole genome comparison revealed the taxonomic position of the WCS
      model strains within the Pseudomonas genus. Despite the enormous diversity of
      Pseudomonas spp. in soils, several plant-associated Pseudomonas spp. strains that
      have been isolated from different hosts at different geographic regions appear to
      be nearly isogenic to WCS358, WCS374, or WCS417. Interestingly, all these WCS
      look-a-likes have been selected because of their plant protective or plant growth
      promoting properties. CONCLUSIONS: The genome sequences of the model WCS strains
      revealed that they can be considered representatives of universally-present plant
      beneficial Pseudomonas spp. With their well-characterized functions in the
      promotion of plant growth and health, the fully sequenced genomes of the WCS
      strains provide a genetic framework that allows for detailed analysis of the
      biological mechanisms of the plant-beneficial traits of these PGPR. Considering
      the increasing focus on the role of the root microbiome in plant health,
      functional genomics of the WCS strains will enhance our understanding of the
      diversity of functions of the root microbiome.

PMID- 26198434
TI  - What's on YOUR Facebook profile? Evaluation of an educational intervention to
      promote appropriate use of privacy settings by medical students on social
      networking sites.
AB  - BACKGROUND: The rise of social media has led to growing concerns about the
      potential implications of 'unprofessional' postings by physicians and medical
      students on individuals, institutions, and the medical profession. Relevant and
      effective guidelines have been difficult to develop and enforce, and there is a
      need for students and physicians to consider how their online activities may be
      perceived in the context of their professional roles. The purpose of this project
      was to examine the Internet presence of a graduating Canadian medical school
      class by scanning students' public profiles on the social media site Facebook,
      incorporate this information into an educational activity addressing
      professionalism and social media, and evaluate the impact of this activity on
      student behavior. METHODS: A systematic search for public Facebook profiles of
      each member of the class was conducted, and data were collected on the types of
      publicly visible material. These were presented as part of an educational session
      on social media and professionalism. One month later, the Facebook search was
      repeated. RESULTS: Of 152 students in the class, profiles were found for 121
      (79.8%). The majority of students used appropriately restrictive privacy
      settings; however, a significant minority had publicly visible information,
      including comments, photographs, location, and status as a medical student. The
      educational innovation was well received with more than 90% of students agreeing
      that this topic was important and well addressed. A follow-up search found that
      many students had altered their privacy settings to make less information
      publicly available. CONCLUSIONS: A small but significant proportion of students
      share potentially unprofessional content on social media. An interactive
      educational intervention, which includes specific disclosure of how participants
      appear to others on social media, resulted in a significant change in student
      behavior.

PMID- 26198435
TI  - A prospective evaluation of ultrasound as a diagnostic tool in acute
      microcrystalline arthritis.
AB  - INTRODUCTION: The performance of ultrasound (US) in the diagnosis of acute gouty
      (MSU) arthritis and calcium pyrophosphate (CPP) arthritis is not yet well
      defined. Most studies evaluated US as the basis for diagnosing crystal arthritis
      in already diagnosed cases of gout and few prospective studies have been
      performed. METHODS: One hundred nine consecutive patients who presented an acute
      arthritis of suspected microcrystalline arthritis were prospectively included.
      All underwent an US of the symptomatic joints(s) and of knees, ankles and 1(st)
      metatarsopalangeal (MTP) joints by a rheumatologist "blinded" to the clinical
      history. 92 also had standard X-rays. Crystal identification was the gold
      standard. RESULTS: Fifty-one patients had MSU, 28 CPP and 9 had both crystals by
      microscopic analysis. No crystals were detected in 21. One had septic arthritis.
      Based on US signs in the symptomatic joint, the sensitivity of US for both gout
      and CPP was low (60% for both). In gout, the presence of US signs in the
      symptomatic joint was highly predictive of the diagnosis (PPV = 92%). When US
      diagnosis was based on an examination of multiple joints, the sensitivity for
      both gout and CPP rose significantly but the specificity and the PPV decreased.
      In the absence of US signs in all the joints studied, CPP arthritis was unlikely
      (NPV = 87%) particularly in patients with no previous crisis (NPV = 94%). X-ray
      of the symptomatic joints was confirmed to be not useful in diagnosing gout and
      was equally sensitive or specific as US in CPP arthritis. CONCLUSIONS:
      Arthrocenthesis remains the key investigation for the diagnosis of
      microcrystalline acute arthritis. Although US can help in the diagnostic process,
      its diagnostic performance is only moderate. US should not be limited to the
      symptomatic joint. Examination of multiple joints gives a better diagnostic
      sensitivity but lower specificity.

PMID- 26198436
TI  - Integrative approaches for signalling and metabolic networks.

PMID- 26198437
TI  - Reclassification of 'Thiobacillus prosperus' Huber and Stetter 1989 as
      Acidihalobacter prosperus gen. nov., sp. nov., a member of the family
      Ectothiorhodospiraceae.
AB  - Analysis of phylogenomic metrics of a recently released draft genome sequence of
      the halotolerant, acidophile 'Thiobacillus prosperus' DSM 5130 indicates that it
      is not a member of the genus Thiobacillus within the class Betaproteobacteria as
      originally proposed. Based on data from 16S rRNA gene phylogeny, and analyses of
      multiprotein phylogeny and average nucleotide identity (ANI), we show that it
      belongs to a new genus within the family Ectothiorhodospiraceae, for which we
      propose the name Acidihalobacter gen. nov. In accordance, it is proposed that
      'Thiobacillus prosperus' DSM 5130 be named Acidihalobacter prosperus gen. nov.,
      sp. nov. DSM 5130T ( = JCM 30709T) and that it becomes the type strain of the
      type species of this genus. 

PMID- 26198438
TI  - Hyperacute Vasospasm After Aneurysmal Subarachnoid Hemorrhage.
AB  - BACKGROUND: Cerebral vasospasm after aneurysmal subarachnoid hemorrhage typically
      occurs 3-14 days after aneurysm rupture. We describe a series of patients who
      developed vasospasm within minutes of aneurysm rupture. This phenomenon, which we
      term, "hyperacute vasospasm," has been reported in animal models of SAH, but
      hitherto has been poorly described in humans. METHODS: Eleven patients were
      identified from an institutional registry who had aneurysmal rupture during
      catheter cerebral angiography between 1997 and 2009. We quantified the degree of
      vasoconstriction using vascular diameter index (VDI). The change in VDI (delta
      VDI or DVDI) was calculated by determining the difference in VDI before and after
      the procedure. We also examined the relationship between hyperacute vasospasm and
      delayed cerebral ischemia. RESULTS: Ten of eleven (91%) patients with
      intraoperative aneurysm rupture had cerebral vasoconstriction within minutes of
      intra-procedural aneurysmal rupture. Six of eleven patients (55%) with hyperacute
      vasospasm developed delayed cerebral infarction. CONCLUSIONS: Hyperacute
      vasospasm is likely common in patients with intraoperative aneurysm rupture and
      may be an unrecognized element of the natural history of aneurysmal subarachnoid
      hemorrhage. In this limited series, there was an association between hyperacute
      vasospasm and delayed cerebral infarction.

PMID- 26198439
TI  - How are children with HIV faring in Nigeria?--a 7 year retrospective study of
      children enrolled in HIV care.
AB  - BACKGROUND: To review the pediatric care and treatment program at Massey Street
      Children Hospital, in Lagos, Nigeria a retrospective analysis of medical records
      focusing on health services, survival and retention in care. METHODS: The
      analysis covered a cohort of children initiated on antiretroviral therapy (ART)
      from 2005 to 2011. In this population, pediatric HIV care was defined as
      initiating ART between ages 0 and 14 years. Treatment initiation and follow-up
      were according to the Nigerian national guidelines for pediatric ART, which are
      based on World Health Organization guidelines adapted to our local context. The
      primary endpoint was mortality measured as cumulative survival. Other outcomes of
      interest included "loss to follow-up", "transferred out", and "stopped
      treatment". RESULTS: Mean (SD) age at ART initiation was 51 (39) months in female
      children and 52 (42) months in male children. After seven years of ART care, 64%
      of the 660 study children were retained in care and on treatment, 16% were lost
      to follow-up, 10% were dead, and 9% had discontinued HIV care at this facility
      for other reasons. World Health Organization disease stage, CD4 count, age, and
      year of ART initiation were highly predictive of mortality, while anemia at
      baseline was not statistically significantly associated. CONCLUSIONS: Overall
      study results suggest a viable pediatric HIV program exists at the study
      facility. Retention rates were lowest for the earliest cohort of infected
      children, which implies long-term challenges. Mother-to-child transmission
      programs need to be dynamic to stem the scourge of pediatric HIV in Nigeria.

PMID- 26198440
TI  - Denosumab in treatment-naive and pre-treated with zoledronic acid postmenopausal
      women with low bone mass: Effect on bone mineral density and bone turnover
      markers.
AB  - PURPOSE: To compare denosumab-induced changes in lumbar spine (LS) and femoral
      neck (FN) bone mineral density (BMD), bone markers and free soluble receptor
      activator of nuclear factor kappaB ligand (sRANKL) between treatment naive
      postmenopausal women with low bone mass (naive group) and those who were
      previously treated with a single zoledronic acid infusion (post-Zol group).
      PROCEDURES: Procollagen type 1N-terminal propeptide (P1NP), C-terminal cross
      linking telopeptide of type 1 collagen (CTx) and sRANKL levels were measured in
      serum samples obtained at baseline and 3, 6 and 12months after denosumab
      initiation. LS and FN BMD were measured at baseline and 12months. RESULTS: LS and
      FN BMD increased significantly in both naive and post-Zol group (p<0.001 and
      p=0.025 vs. p<0.001 and p=0.017, respectively). Despite the higher P1NP and CTx
      levels in naive patients at baseline (both p<0.001), denosumab caused comparable
      decreases in both groups at month 3, which returned to post-Zol group baseline
      levels at month 6 and 12 in all patients. Similarly, sRANKL levels decreased
      significantly at month 3 in both groups and returned to baseline levels at months
      6 and 12. CONCLUSIONS: In patients previously treated with zoledronic acid,
      sequential denosumab treatment is effective in terms of BMD increases and bone
      turnover suppression. Despite the lower baseline levels in patients pre-treated
      with zoledronic acid, bone markers are similarly decreased in both groups
      following denosumab administration and maintain their reversibility. Denosumab
      reversibly suppresses endogenous free sRANKL levels in both naive and zoledronic
      acid pre-treated patients.

PMID- 26198441
TI  - Endothelium-enriched microRNAs as diagnostic biomarkers for cardiac allograft
      vasculopathy.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is a limiting factor for the
      long-term survival of heart transplant recipients. Clinical decisions and care
      may be improved by the development of prediction models based on circulating
      biomarkers. The endothelium may play a central pathogenetic role in the
      development of CAV. We evaluated the hypothesis that endothelium-enriched
      microRNAs (miRNAs) discriminate between patients with and without CAV. METHODS:
      This cross-sectional study recruited 52 patients undergoing coronary angiography
      between 5 and 15 years after heart transplantation. Circulating levels of
      endothelium-enriched miRNAs (miR-21-5p, miR-92a-3p, miR-92a-1-5p, miR-126-3p, and
      miR-126-5p) were quantified by real-time reverse transcription polymerase chain
      reaction. The discriminative ability of logistic regression models was evaluated
      using the concordance (C) statistic. RESULTS: Median plasma levels of miR-210-5p,
      miR-92a-3p, miR-126-3p, and miR-126-5p were 1.82-fold (p = not significant), 1.87
      fold (p < 0.05), 1.94-fold (p = 0.074), and 1.59-fold (p = 0.060) higher in
      patients with CAV than in patients without CAV. Recipient age (C statistic =
      0.689; 95% confidence interval [CI], 0.537-0.842), and levels of serum creatinine
      (C statistic = 0.703; 95% CI, 0.552-0.854), miR-92a-3p (C statistic = 0.682; 95%
      CI, 0.533-0.831), and miR-126-5p (C statistic = 0.655; 95% CI, 0.502-0.807)
      predicted CAV status in univariable models. In multivariable logistic regression
      models with recipient age and creatinine as covariates, miR-126-5p (chi-square =
      4.37(1), p = 0.037), miR-92a-3p (chi-square = 6.01(1), p = 0.014), and the
      combination of miR-126-5p and miR-92a-3p (chi-square = 8.16(2), p = 0.017) added
      significant information. The model with age, creatinine, miR-126-5p, and miR-92a
      3p as covariables conferred good discrimination between patients without and with
      CAV (C statistic = 0.800; 95% CI, 0.674-0.926). CONCLUSIONS: Endothelium-enriched
      miRNAs have diagnostic ability for CAV beyond clinical predictors.

PMID- 26198442
TI  - Dexamethasone but not tacrolimus suppresses TNF-alpha-induced thymic stromal
      lymphopoietin expression in lesional keratinocytes of atopic dermatitis model.
AB  - BACKGROUND: Thymic stromal lymphopoietin (TSLP) initiates the Th2-type allergic
      inflammation, and is thought to play an important role in the pathogenesis of
      atopic dermatitis (AD). TNF-alpha is a key cytokine which is involved in the
      pathophysiology of various inflammatory diseases, and the expression level is
      elevated in the sera and skin of patients with AD. In addition, TNF-alpha has
      been reported to induce TSLP expression in epidermal keratinocytes. Topical
      glucocorticoids and calcineurin inhibitors are safe and effective agents for AD,
      but the effects of these agents on TNF-alpha-induced TSLP expression are not
      fully understood. OBJECTIVE: To investigate whether the glucocorticosteroid
      dexamethasone and the calcineurin inhibitor tacrolimus could affect TSLP
      expression induced by TNF-alpha in lesional keratinocytes of AD. METHODS: The
      effects of topical dexamethasone and tacrolimus on TSLP expression were evaluated
      in an AD mouse model induced by repeated 2,4,6-trinitro-1-chlorobenzene
      application. Co-immunostaining for TSLP and TNF-alpha was performed using skin
      samples from AD patients and the mouse model. Normal human epidermal
      keratinocytes (NHEKs) were cultured with dexamethasone or tacrolimus in the
      presence of TNF-alpha to analyze TSLP expression. RESULTS: Topical application of
      dexamethasone but not tacrolimus repressed TSLP expression in the mouse model.
      TSLP and TNF-alpha showed similar distribution pattern in epidermal keratinocytes
      of AD lesions and the mouse model. TSLP expression was induced by TNF-alpha via
      NF-kappaB in a dose-dependent and an autocrine and/or paracrine manner in NHEKs,
      which was significantly suppressed by dexamethasone but not by tacrolimus.
      Similarly to TSLP expression, IL-6, TNF-alpha, IL-8, and IL-36gamma expression
      induced by TNF-alpha were significantly suppressed by dexamethasone but not by
      tacrolimus in NHEKs. CONCLUSION: Dexamethasone but not tacrolimus suppresses the
      TSLP expression induced by TNF-alpha in lesional keratinocytes of AD model. Our
      observations uncover the unreported functional difference between topical
      glucocorticosteroids and calcineurin inhibitors in cutaneous inflammatory
      diseases.

PMID- 26198443
TI  - Carriage of meticillin-susceptible and -resistant Staphylococcus aureus by
      medical students in Hong Kong.

PMID- 26198444
TI  - Persistent Disparities Among Patients With T-Cell Non-Hodgkin Lymphomas and B
      Cell Diffuse Large Cell Lymphomas Over 40 Years: A SEER Database Review.
AB  - BACKGROUND: As of 2013, more than 550,000 people are living with non-Hodgkin
      lymphoma (NHL). PATIENTS AND METHODS: We undertook a large Surveillance
      Epidemiology and End Results (SEER) based analysis to describe outcome
      disparities in different subgroups of aggressive T-cell and B-cell NHL patients,
      with a focus on various ethnicities. RESULTS: The final analysis included 7662
      patients with T-cell and 84,910 with B-cell NHL. Survival analysis revealed that
      male sex and increasing age were independent predictors of worse overall survival
      (OS; P < .001). For aggressive T-cell NHL, there was no significant improvement
      in median OS between 1973 and 2011 (P = .081), and ethnic minorities (Asians,
      Hispanics, and African Americans) had significantly worse OS than whites (P <
      .001). There were similar trends for age, sex, and race for diffuse large B-cell
      NHL, but a significant improvement in median OS was seen over time (P < .001).
      CONCLUSION: These results are the first to elicit outcomes in a broad
      classification of ethnic minorities and underscore the urgency for development of
      novel therapeutics, especially in T-cell NHL. In addition, in-depth studies of
      disease biology and health care utilization are required for better triage of
      health care resources, especially for ethnic minorities.

PMID- 26198446
TI  - Sonic Hedgehog, VACTERL, and Fanconi anemia: Pathogenetic connections and
      therapeutic implications.
AB  - Three systems with VACTERL association findings- mutations of the Sonic Hedgehog
      (SHH) signaling pathway in mice, murine adriamycin teratogenicity, and human
      Fanconi anemia (FA) pathway mutations, may all involve a similar mechanism. SHH
      is up-regulated in irradiated cells, and DNA breaks common with radiation damage
      in the adriamycin and FA systems are plausible signals for such effects, which
      would affect development. Since FA related DNA breakage occurs throughout life,
      SHH disturbances may account for later FA related findings involving
      hematopoietic and malignancy issues. In support, androgen, a standard treatment
      for FA hematologic failure, down-regulates SHH, and common FA malignancies such
      as squamous cell carcinomas and acute myeloid leukemia have been linked to
      enhanced SHH function. This suggests that interventions lowering SHH levels may
      be useful therapeutically. Also supporting a connection between pre- and post-
      natal findings, the frequency and number of VACTERL anomalies with FA correlate
      with the severity and onset of hematopoietic and malignancy issues. In FA, radial
      anomalies are the most common of these defects, followed by renal findings, while
      vertebral and gastrointestinal anomalies are relatively uncommon, a pattern that
      differs from observations of the VACTERL association. Genes with more severe
      effects also show a greatly increased incidence of brain abnormalities, and a
      paucity of such findings with other FA genes suggests that brain development is
      relatively refractory to SHH related effects, accounting for the rarity of such
      findings with the association.

PMID- 26198445
TI  - Prenatal mercury exposure, autism, and developmental delay, using pharmacokinetic
      combination of newborn blood concentrations and questionnaire data: a case
      control study.
AB  - BACKGROUND: Methylmercury (MeHg), known for well over a century as a neurotoxin
      in adults, has more recently been studied for potential detrimental effects
      during early brain development. While several studies have estimated mercury
      exposure, they usually rely on either a single biomarker or questionnaire data,
      each of which has limitations. The goal of this paper was to develop a
      toxicokinetic model that incorporates both biomarker and questionnaire data to
      estimate the cumulative exposure to MeHg through seafood consumption using data
      collected from the Childhood Autism Risks from Genetics and the Environment
      (CHARGE) study. METHODS: We utilized a previously described discrete-time model
      that estimates blood MeHg concentration given a piecewise-constant ingestion rate
      and single-compartment pharmacokinetics. We measured newborn bloodspot Hg
      concentrations and obtained information pertaining to maternal fish consumption
      using a questionnaire. Using MeHg concentration estimates from the toxicokinetic
      model, cumulative MeHg exposure was estimated in children with autism, children
      with developmental delay, and typically developing children. Median estimated
      cumulative MeHg was compared among diagnostic groups using the Kruskal-Wallis
      Test. Multinomial logistic regression models were constructed to assess the
      association between cumulative MeHg concentration and the risk of autism and
      developmental delay (vs. typical development). RESULTS: The estimated average
      MeHg concentration of for all fish species consumed by mothers was 42 ppb. Median
      cumulative MeHg over gestation was similar across diagnostic groups (p-values
      raged from 0.91 to 0.98). After adjusting for potential confounding, we found no
      association between cumulative MeHg exposure and the risk of autism (OR = 0.95,
      95% CI: 0.95, 1.12) or developmental delay (OR = 1.00, 95% CI: 0.89, 1.13).
      CONCLUSIONS: The toxicokinetic model described in this paper yielded fish MeHg
      concentration estimates that are consistent with fish species containing lower
      levels of MeHg. Overall, cumulative MeHg exposure does not appear to detectably
      elevate the risk of autism or developmental delay. Based on the regression
      standard error for the association between ASD and TD, we would have reported
      statistical significance for an adjusted odds ratio of 1.09 or larger. This
      method can easily be extended to other epidemiologic studies in which there is a
      biomarker measurement and questionnaire data regarding exposure.

PMID- 26198447
TI  - Design, Synthesis and Optoelectronic Properties of Unsymmetrical Oxadiazole Based
      Indene Substituted Derivatives as Deep Blue Fluoroscent Materials.
AB  - A series of novel unsymmetrically substituted indene-oxadiazole derivatives (3a
      f) have been designed and synthesized by employing palladium catalysed Suzuki
      cross coupling reaction in high yields. The structural integrity of all the novel
      compounds was established by (1)H, (13)C NMR and LC/MS analysis. These compounds
      are amorphous in nature and are remarkably stable to long term storage under
      ambient conditions. The optoelectronic properties have been studied in detail
      using UV-Vis absorption and Fluorescence spectroscopy. All compounds emit intense
      blue to green-blue fluoroscence with high quantum yields. Time resolved
      measurments have shown life times in the range of 1.28 to 4.51 ns. The density
      functional theory (DFT) calculations were carried out for all the molecules to
      understand their structure-property relationships. Effect of concentration
      studies has been carried out in different concentrations for both absorption and
      emission properties and from this we have identified the optimized fluoroscence
      concentrations for all these compounds. The indene substituted anthracene
      oxadiazole derivative (3f) showed significant red shift (lambdamax (emi) = 490
      nm) and emits intense green-blue fluoroscence with largest stokes shift of 145
      nm. This compound also exhibited highest fluoroscence life time (tau) of 4.51 ns,
      which is very close to the standard dye coumarin-540A (4.63 ns) and better than
      fluorescein-548 (4.10 ns). The results demonstrated that the novel unsymmetrical
      indene-substituted oxadiazole derivatives could play important role in organic
      optoelectronic applications, such as organic light-emitting diodes (OLEDs) or as
      models for investigating the fluorescent structure-property relationship of the
      indene-functionalized oxadiazole derivatives. 

PMID- 26198448
TI  - Hemodynamics of a functional centrifugal-flow total artificial heart with
      functional atrial contraction in goats.
AB  - Implantation of a total artificial heart (TAH) is one of the therapeutic options
      for the treatment of patients with end-stage biventricular heart failure. There
      is no report on the hemodynamics of the functional centrifugal-flow TAH with
      functional atrial contraction (fCFTAH). We evaluated the effects of pulsatile
      flow by atrial contraction in acute animal models. The goats received fCFTAH that
      we created from two centrifugal-flow ventricular assist devices. Some hemodynamic
      parameters maintained acceptable levels: heart rate 115.5 +/- 26.3 bpm, aortic
      pressure 83.5 +/- 10.1 mmHg, left atrial pressure 18.0 +/- 5.9 mmHg, pulmonary
      pressure 28.5 +/- 9.7 mmHg, right atrial pressure 13.6 +/- 5.2 mmHg, pump flow
      4.0 +/- 1.1 L/min (left) 3.9 +/- 1.1 L/min (right), and cardiac index 2.13 +/-
      0.14 L/min/m(2). fCFTAH with atrial contraction was able to maintain the TAH
      circulation by forming a pulsatile flow in acute animal experiments. Taking the
      left and right flow rate balance using the low internal pressure loss of the VAD
      pumps may be easier than by other pumps having considerable internal pressure
      loss. We showed that the remnant atrial contraction effected the flow rate change
      of the centrifugal pump, and the atrial contraction waves reflected the heart
      rate. These results indicate that remnant atria had the possibility to preserve
      autonomic function in fCFTAH. We may control fCFTAH by reflecting the autonomic
      function, which is estimated with the flow rate change of the centrifugal pump.

PMID- 26198449
TI  - Neurotoxic 1-deoxysphingolipids and paclitaxel-induced peripheral neuropathy.
AB  - Peripheral neuropathy is a major dose-limiting side effect of paclitaxel and
      cisplatin chemotherapy. In the current study, we tested the involvement of a
      novel class of neurotoxic sphingolipids, the 1-deoxysphingolipids. 1
      Deoxysphingolipids are produced when the enzyme serine palmitoyltransferase uses
      l-alanine instead of l-serine as its amino acid substrate. We tested whether
      treatment of cells with paclitaxel (250 nM, 1 uM) and cisplatin (250 nM, 1 uM)
      would result in elevated cellular levels of 1-deoxysphingolipids. Our results
      revealed that paclitaxel, but not cisplatin treatment, caused a dose-dependent
      elevation of 1-deoxysphingolipids levels and an increase in the message and
      activity of serine palmitoyltransferase (P < 0.05). We also tested whether there
      is an association between peripheral neuropathy symptoms [evaluated by the
      European Organization for Research and Treatment of Cancer (EORTC) QLQ
      chemotherapy-induced peripheral neuropathy-20 (CIPN20) instrument] and the 1
      deoxysphingolipid plasma levels (measured by mass spectrometry) in 27 patients
      with breast cancer who were treated with paclitaxel chemotherapy. Our results
      showed that there was an association between the incidence and severity of
      neuropathy and the levels of very-long-chain 1-deoxyceramides such as C24 (P <
      0.05), with the strongest association being with motor neuropathy (P < 0.001).
      Our data from cells and from patients with breast cancer suggest that 1
      deoxysphingolipids, the very-long-chain in particular, play a role as molecular
      intermediates of paclitaxel-induced peripheral neuropathy.

PMID- 26198450
TI  - Quantifying phenotypic flexibility as the response to a high-fat challenge test
      in different states of metabolic health.
AB  - Metabolism maintains homeostasis at chronic hypercaloric conditions, activating
      postprandial response mechanisms, which come at the cost of adaptation processes
      such as energy storage, eventually with negative health consequences. This study
      quantified the metabolic adaptation capacity by studying challenge response
      curves. After a high-fat challenge, the 8 h response curves of 61 biomarkers
      related to adipose tissue mass and function, systemic stress, metabolic
      flexibility, vascular health, and glucose metabolism was compared between 3
      metabolic health stages: 10 healthy men, before and after 4 wk of high-fat, high
      calorie diet (1300 kcal/d extra), and 9 men with metabolic syndrome (MetS). The
      MetS subjects had increased fasting concentrations of biomarkers representing the
      3 core processes, glucose, TG, and inflammation control, and the challenge
      response curves of most biomarkers were altered. After the 4 wk hypercaloric
      dietary intervention, these 3 processes were not changed, as compared with the
      preintervention state in the healthy subjects, whereas the challenge response
      curves of almost all endocrine, metabolic, and inflammatory processes regulating
      these core processes were altered, demonstrating major molecular physiologic
      efforts to maintain homeostasis. This study thus demonstrates that change in
      challenge response is a more sensitive biomarker of metabolic resilience than are
      changes in fasting concentrations.

PMID- 26198451
TI  - Daily oral iron supplementation during pregnancy.
AB  - BACKGROUND: Iron and folic acid supplementation has been the preferred
      intervention to improve iron stores and prevent anaemia among pregnant women, and
      it is thought to improve other maternal and birth outcomes. OBJECTIVES: To assess
      the effects of daily oral iron supplements for pregnant women, either alone or in
      conjunction with folic acid, or with other vitamins and minerals as a public
      health intervention in antenatal care. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (10 January 2015). We also
      searched the WHO International Clinical Trials Registry Platform (ICTRP) (26
      February 2015) and contacted relevant organisations for the identification of
      ongoing and unpublished studies (26 February 2015) . SELECTION CRITERIA:
      Randomised or quasi-randomised trials evaluating the effects of oral preventive
      supplementation with daily iron, iron + folic acid or iron + other vitamins and
      minerals during pregnancy. DATA COLLECTION AND ANALYSIS: We assessed the
      methodological quality of trials using standard Cochrane criteria. Two review
      authors independently assessed trial eligibility, extracted data and conducted
      checks for accuracy. We used the GRADE approach to assess the quality of the
      evidence for primary outcomes.We anticipated high heterogeneity among trials and
      we pooled trial results using a random-effects model and were cautious in our
      interpretation of the pooled results: the random-effects model gives the average
      treatment effect. MAIN RESULTS: We included 61 trials. Forty-four trials,
      involving 43,274 women, contributed data and compared the effects of daily oral
      supplements containing iron versus no iron or placebo.Preventive iron
      supplementation reduced maternal anaemia at term by 70% (risk ratio (RR) 0.30;
      95% confidence interval (CI) 0.19 to 0.46, 14 trials, 2199 women, low quality
      evidence), iron-deficiency anaemia at term (RR 0.33; 95% CI 0.16 to 0.69, six
      trials, 1088 women), and iron deficiency at term by 57% (RR 0.43; 95% CI 0.27 to
      0.66, seven trials, 1256 women, low quality evidence). There were no clear
      differences between groups for severe anaemia in the second or third trimester,
      or maternal infection during pregnancy (RR 0.22; 95% CI 0.01 to 3.20, nine
      trials, 2125 women, very low quality evidence; and, RR 1.21; 95% CI 0.33 to 4.46;
      one trial, 727 women, low quality evidence, respectively), or maternal mortality
      (RR 0.33; 95% CI 0.01 to 8.19, two trials, 12,560 women, very low quality
      evidence), or reporting of side effects (RR 1.29; 95% CI 0.83 to 2.02, 11 trials,
      2423 women, very low quality evidence). Women receiving iron were on average more
      likely to have higher haemoglobin (Hb) concentrations at term and in the
      postpartum period, but were at increased risk of Hb concentrations greater than
      130 g/L during pregnancy, and at term.Compared with controls, women taking iron
      supplements less frequently had low birthweight newborns (8.4% versus 10.3%,
      average RR 0.84; 95% CI 0.69 to 1.03, 11 trials, 17,613 women, low quality
      evidence), and preterm babies (RR 0.93; 95% CI 0.84 to 1.03, 13 trials, 19,286
      women, moderate quality evidence). They appeared to also deliver slightly heavier
      babies (mean difference (MD) 23.75; 95% CI -3.02 to 50.51, 15 trials, 18,590
      women, moderate quality evidence). None of these results were statistically
      significant. There were no clear differences between groups for neonatal death
      (RR 0.91; 95% CI 0.71 to 1.18, four trials, 16,603 infants, low quality
      evidence), or congenital anomalies (RR 0.88, 95% CI 0.58 to 1.33, four trials,
      14,636 infants, low quality evidence).Twenty-three studies were conducted in
      countries that in 2011 had some malaria risk in parts of the country. In some of
      these countries/territories, malaria is present only in certain areas or up to a
      particular altitude. Only two of these studies reported malaria outcomes. There
      is no evidence that iron supplementation increases placental malaria. For some
      outcomes heterogeneity was higher than 50%. AUTHORS' CONCLUSIONS: Supplementation
      reduces the risk of maternal anaemia and iron deficiency in pregnancy but the
      positive effect on other maternal and infant outcomes is less clear.
      Implementation of iron supplementation recommendations may produce heterogeneous
      results depending on the populations' background risk for low birthweight and
      anaemia, as well as the level of adherence to the intervention.

PMID- 26198452
TI  - Examining the relationship between marijuana use, medical marijuana dispensaries,
      and abusive and neglectful parenting.
AB  - The current study extends previous research by examining whether and how current
      marijuana use and the physical availability of marijuana are related to child
      physical abuse, supervisory neglect, or physical neglect by parents while
      controlling for child, caregiver, and family characteristics in a general
      population survey in California. Individual level data on marijuana use and
      abusive and neglectful parenting were collected during a telephone survey of
      3,023 respondents living in 50 mid-size cities in California. Medical marijuana
      dispensaries and delivery services data were obtained via six websites and
      official city lists. Data were analyzed using negative binomial and linear mixed
      effects multilevel models with individuals nested within cities. Current
      marijuana use was positively related to frequency of child physical abuse and
      negatively related to physical neglect. There was no relationship between
      supervisory neglect and marijuana use. Density of medical marijuana dispensaries
      and delivery services was positively related to frequency of physical abuse. As
      marijuana use becomes more prevalent, those who work with families, including
      child welfare workers must screen for how marijuana use may affect a parent's
      ability to provide for care for their children, particularly related to physical
      abuse. 

PMID- 26198453
TI  - Mass spectrometric imaging of in vivo protein and lipid adsorption on
      biodegradable vascular replacement systems.
AB  - Cardiovascular diseases present amongst the highest mortality risks in Western
      civilization and are frequently caused by arteriosclerotic vessel failure.
      Coronary artery and peripheral vessel reconstruction necessitates the use of
      small diameter systems that are mechanically stress-resistant and biocompatible.
      Expanded polytetrafluorethylene (ePTFE) is amongst the materials used most
      frequently for non-degradable and bio-degradable vessel reconstruction
      procedures, with thermoplastic polyurethanes (TPU) representing a promising
      substitute. The present study describes and compares the biological adsorption
      and diffusion occurring with both materials following implantation in rat models.
      Gel electrophoresis and thin-layer chromatography, combined with mass
      spectrometry and mass spectrometry imaging, were utilized to identify the
      adsorbed lipids and proteins. The results were compared with the analytes present
      in native aorta tissue. It was revealed that both polymers were severely affected
      by biological adsorption after 10 min in vivo. Proteins associated with cell
      growth and migration were identified, especially on the luminal graft surface,
      while lipids were found to be located on both the luminal and abluminal surfaces.
      Lipid adsorption and cholesterol diffusion were found to be correlated with the
      polymer modifications identified on degradable thermoplastic urethane graft
      samples, with the latter revealing extensive cholesterol adsorption. The present
      study demonstrates an interaction between biological matter and both graft
      materials, and provides insights into polymer changes, in particular, those
      observed with thermoplastic urethanes already after 10 min in vivo exposure.
      ePTFE demonstrated minor polymer modifications, whereas several different polymer
      signals were observed for TPU, all were co-localized with biological signals. 

PMID- 26198454
TI  - Approximate score-based testing with application to multivariate trait
      association analysis.
AB  - For genome-wide association studies and DNA sequencing studies, several powerful
      score-based tests, such as kernel machine regression and sum of powered score
      tests, have been proposed in the last few years. However, extensions of these
      score-based tests to more complex models, such as mixed-effects models for
      analysis of multiple and correlated traits, have been hindered by the
      unavailability of the score vector, due to either no output from statistical
      software or no closed-form solution at all. We propose a simple and general
      method to asymptotically approximate the score vector based on an asymptotically
      normal and consistent estimate of a parameter vector to be tested and its
      (consistent) covariance matrix. The proposed method is applicable to both maximum
      likelihood estimation and estimating function-based approaches. We use the
      derived approximate score vector to extend several score-based tests to mixed
      effects models. We demonstrate the feasibility and possible power gains of these
      tests in association analysis of multiple and correlated quantitative or binary
      traits with both real and simulated data. The proposed method is easy to
      implement with a wide applicability. 

PMID- 26198455
TI  - The clinical utility of basophil activation testing in diagnosis and monitoring
      of allergic disease.
AB  - The basophil activation test (BAT) has become a pervasive test for allergic
      response through the development of flow cytometry, discovery of activation
      markers such as CD63 and unique markers identifying basophil granulocytes.
      Basophil activation test measures basophil response to allergen cross-linking IgE
      on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous
      activation is assessed as the fraction of reacting basophils. In addition to
      clinical history, skin prick test, and specific IgE determination, BAT can be a
      part of the diagnostic evaluation of patients with food-, insect venom-, and drug
      allergy and chronic urticaria. It may be helpful in determining the clinically
      relevant allergen. Basophil sensitivity may be used to monitor patients on
      allergen immunotherapy, anti-IgE treatment or in the natural resolution of
      allergy. Basophil activation test may use fewer resources and be more
      reproducible than challenge testing. As it is less stressful for the patient and
      avoids severe allergic reactions, BAT ought to precede challenge testing. An
      important next step is to standardize BAT and make it available in diagnostic
      laboratories. The nature of basophil activation as an ex vivo challenge makes it
      a multifaceted and promising tool for the allergist. In this EAACI task force
      position paper, we provide an overview of the practical and technical details as
      well as the clinical utility of BAT in diagnosis and management of allergic
      diseases.

PMID- 26198456
TI  - Understanding the basis of I50V-induced affinity decrease in HIV-1 protease via
      molecular dynamics simulations using polarized force field.
AB  - Human immunodeficiency virus (HIV)-1 protease is one of the most promising drug
      target commonly utilized to combat Acquired Immune Deficiency Syndrome (AIDS).
      However, with the emergence of drug resistance arising from mutations, the
      efficiency of protease inhibitors (PIs) as a viable treatment for AIDS has been
      greatly reduced. I50V mutation as one of the most significant mutations occurring
      in HIV-1 protease will be investigated in this study. Molecular dynamics (MD)
      simulation was utilized to examine the effect of I50V mutation on the binding of
      two PIs namely indinavir and amprenavir to HIV-1 protease. Prior to the
      simulations conducted, the electron density distributions of the PI and each
      residue in HIV-1 protease are derived by combining quantum fragmentation approach
      molecular fractionation with conjugate caps and Poisson-Boltzmann solvation model
      based on polarized protein-specific charge scheme. The atomic charges of the
      binding complex are subsequently fitted using delta restrained electrostatic
      potential (delta-RESP) method to overcome the poor charge determination of buried
      atom. This way, both intraprotease polarization and the polarization between
      protease and the PI are incorporated into partial atomic charges. Through this
      study, the mutation-induced affinity variations were calculated and significant
      agreement between experiments and MD simulations conducted was observed for both
      HIV-1 protease-drug complexes. In addition, the mechanism governing the decrease
      in the binding affinity of PI in the presence of I50V mutation was also explored
      to provide insights pertaining to the design of the next generation of anti-HIV
      drugs.

PMID- 26198457
TI  - Associations of health behaviours with return to work outcomes after colorectal
      cancer.
AB  - PURPOSE: Engaging in positive health behaviours can improve quality of life
      amongst cancer survivors, whether this facilitates return to work is unknown. We
      examined associations of health behaviours with return to work outcomes following
      a diagnosis of colorectal cancer in middle-aged men and women (45-64 years).
      METHODS: We recruited 239 participants through the Queensland Cancer Registry
      between January 2010 and September 2011. Data were collected through telephone
      administered interviews and postal questionnaires at 6 and 12 months post
      diagnosis. Logistic regression examined likelihood of ceasing or reducing work,
      and Cox regression examined factors associated with time to return to work.
      RESULTS: No significant associations were observed between health behaviours
      (fruit and vegetables consumption, alcohol consumption, smoking status, physical
      activity or sitting time) at 6 months and ceasing or reducing work at 12 months
      post-diagnosis. Participants who reported excessive sleep (>=9 h/day) were 2.69
      times more likely to reduce work time or retire (relative to those sleeping the
      recommended 7 to <9 h/day; 95 % CI 1.06, 6.87, adjusted for cancer treatment). In
      Cox regression analysis, excessive sleep was associated with a longer work re
      entry time (relative to sleeping 7 to <9 h/day; HR = 0.47; 95 % CI 0.22, 1.00,
      adjusted for education and cancer treatment). CONCLUSIONS: Further research into
      how excessive sleep might be related to return to work amongst colorectal cancer
      survivors is warranted. Interventions focused on achieving optimal sleep patterns
      may assist colorectal cancer survivors to return to work and should be tested in
      future studies.

PMID- 26198459
TI  - In reference to the usefulness of the stay suture technique in tracheostomy.

PMID- 26198458
TI  - Mapping of seedling resistance in barley to Puccinia striiformis f. sp.
      pseudohordei.
AB  - The barley grass stripe rust (BGYR) pathogen Puccinia striiformis f. sp.
      pseudohordei was first detected in Australia in 1997. While studies have
      established that it is virulent on wild barley grass, and can infect several
      barley cultivars, the basis of genetic resistance to this pathogen in barley is
      largely unknown. Understanding the genetic basis of host resistance and ensuring
      the selection of germplasm with multiple resistance genes are important to
      mitigate the potential impact of BGYR in barley production. Genetic analysis of
      seedling resistance to BGYR in two barley doubled haploid populations, Amaji
      Nijo/WI2585 (AN/WI) and Galleon/Haruna Nijo (GL/HN), indicated that resistance is
      governed by several genes. Marker regression analysis of the seedling resistance
      data from the AN/WI population detected a major QTL, BGYR_WI1 (resistance
      contributed by WI2585 with the closest marker explaining 52 % of the total
      phenotypic effect) on chromosome 1HS, flanked by the loci Xabg59 and Xabc310b at
      map positions 0.0 and 6.9 cM, respectively. Similarly, a major QTL, BGYR_HN1,
      (resistance contributed by Haruna Nijo with the closest marker explaining 70 % of
      the total phenotypic effect) was detected in the GL/HN population and was mapped
      to 1HS, flanked by the loci Xbcd135 and XHOR1 at map positions 12.8 and 24.5 cM,
      respectively. In addition, several minor loci that provided resistance against
      BGYR were detected in both populations. While defined QTL intervals were large,
      the analysis nonetheless provides new information on sources of major QTL
      controlling resistance to BGYR.

PMID- 26198460
TI  - Study on Self-Assembled Well-Defined PEG Graft Copolymers as Efficient Drug
      Loaded Nanoparticles for Anti-Inflammatory Therapy.
AB  - The core-shell micelles in aqueous solutions were prepared at low CAC values
      (<0.1 mg . mL(-1) ) from amphiphilic graft copolymers consisting of poly(methyl
      methacrylate) backbone (120-165 units) with loosely grafted (17-40%) hydroxyl
      capped PEG (9 vs 6 units in side chain) for drug loading. Hydrophobic
      indomethacin (IMC) was loaded into the micelles with content of 22-88%.
      Hydrodynamic diameters of particles were ranged in 110-200 nm. In vitro release
      experiments at various pH indicated faster releasing of IMC at pH 7.4 than that
      at pH 5.0. The studies on micellization, drug loading and release profiles
      verified the cumulative influence of hydrophilic/hydrophobic balance, degree of
      grafting, length of PEG side chains giving advantages in macromolecular design of
      nanocarriers in drug delivery. 

PMID- 26198463
TI  - Controlled Smart Anisotropic Unidirectional Spreading of Droplet on a Fibrous
      Surface.
AB  - Smart anisotropic-unidirectional spreading is displayed on a wettable-gradient
      aligned fibrous surface due to a synergetic directing effect from the aligned
      structure and the ratio of hydrophilic components. 

PMID- 26198462
TI  - Cis- and trans-regulation in X inactivation.
AB  - Female mammalian cells compensate dosage of X-linked gene expression through the
      inactivation of one of their two X chromosomes. X chromosome inactivation (XCI)
      in eutherians is dependent on the non-coding RNA Xist that is up-regulated from
      the future inactive X chromosome, coating it and recruiting factors involved in
      silencing and altering its chromatin state. Xist lies within the X-inactivation
      center (Xic), a region on the X that is required for XCI, and is regulated in cis
      by elements on the X chromosome and in trans by diffusible factors. In this
      review, we summarize the latest results in cis- and trans-regulation of the Xic.
      We discuss how the organization of the Xic in topologically associating domains
      is important for XCI (cis-regulation) and how proteins in the pluripotent state
      and upon development or differentiation of embryonic stem cells control proper
      inactivation of one X chromosome (trans-regulation). 

PMID- 26198464
TI  - Casein/natamycin edible films efficiency for controlling mould growth and on
      microbiological, chemical and sensory properties during the ripening of Kashar
      cheese.
AB  - BACKGROUND: The objective of the present study was to investigate the effects of
      the dipping application of coating materials such as casein (Cas),
      casein/natamycin (Cas/N) and natamycin (N) solutions on chemical (e.g. pH, dry
      matter, fat, acidity, salt, protein, water-soluble nitrogen, ripening index, 12%
      trichloroacetic acid-soluble nitrogen and pH 4.6 soluble nitrogen), microbial
      (e.g. total number of aerobic mesophilic bacteria, lactic acid bacteria in MRS,
      lactic acid bacteria in M17, coliforms and mould) and organoleptic properties of
      Kashar cheese samples during ripening (3, 30, 60 and 90 days). RESULTS: The
      difference in microbiological and chemical changes between samples were found to
      be significant (P < 0.05) during the ripening period. The highest and lowest
      mould counts were determined for the control (2.87 log cfu g(-1) ) and the Cas/N
      (<1 log cfu g(-1) ) samples, respectively, at 90 days of ripening. Compared to
      other cheeses, control and Cas/N-coated cheeses had higher levels of water
      soluble nitrogen and ripening index at in the end of storage. The Cas/N-coated
      cheese samples were preferred more by the panellists, while N-coated cheese
      samples received the lowest scores. CONCLUSION: This study suggests that coating
      could be used to improve the quality of Kashar cheese during ripening.

PMID- 26198465
TI  - Same day discharge after transcatheter aortic valve replacement: Are we there
      yet?
AB  - Early discharge after transcatheter aortic valve replacement (TAVR) has been
      increasingly reported, and is now becoming routinely performed in experienced
      TAVR centers. However, to the best of our knowledge, no case has been described
      where a patient was safely discharged on the same the day of the procedure. This
      report will present the case of a patient who underwent a successful transfemoral
      TAVR and was safely discharged home the same day. Specific requirements and
      criteria are proposed to ensure the safety of this approach.

PMID- 26198467
TI  - Gap analysis of infection control practices in low- and middle-income countries.
AB  - BACKGROUND: Healthcare-associated infection rates are higher in low- and middle
      income countries compared with high-income countries, resulting in relatively
      larger incidence of patient mortality and disability and additional healthcare
      costs. OBJECTIVE: To use the Infection Control Assessment Tool to assess gaps in
      infection control (IC) practices in the participating countries. METHODS: Six
      international sites located in Argentina, Greece, Hungary, India, Nepal, and
      South Africa provided information on the health facility and the surgical modules
      relating to IC programs, surgical antibiotic use and surgical equipment
      procedures, surgical area practices, sterilization and disinfection of equipment
      and intravenous fluid, and hand hygiene. Modules were scored for each country.
      RESULTS: The 6 international sites completed 5 modules. Of 121 completed
      sections, scores of less than 50% of the recommended IC practices were received
      in 23 (19%) and scores from 50% to 75% were received in 43 (36%). IC programs had
      various limitations in many sites and surveillance of healthcare-associated
      infections was not consistently performed. Lack of administration of
      perioperative antibiotics, inadequate sterilization and disinfection of
      equipment, and paucity of hand hygiene were found even in a high-income country.
      There was also a lack of clearly written defined policies and procedures across
      many facilities. CONCLUSIONS: Our results indicate that adherence to recommended
      IC practices is suboptimal. Opportunities for improvement of IC practices exist
      in several areas, including hospital-wide IC programs and surveillance,
      antibiotic stewardship, written and posted guidelines and policies across a range
      of topics, surgical instrument sterilization procedures, and improved hand
      hygiene.

PMID- 26198466
TI  - A virtual approach to evaluate therapies for management of multiple myeloma
      induced bone disease.
AB  - Multiple myeloma bone disease is devastating for patients and a major cause of
      morbidity. The disease leads to bone destruction by inhibiting osteoblast
      activity while stimulating osteoclast activity. Recent advances in multiple
      myeloma research have improved our understanding of the pathogenesis of multiple
      myeloma-induced bone disease and suggest several potential therapeutic
      strategies. However, the effectiveness of some potential therapeutic strategies
      still requires further investigation and optimization. In this paper, a recently
      developed mathematical model is extended to mimic and then evaluate three
      therapies of the disease, namely: bisphosphonates, bortezomib and TGF-beta
      inhibition. The model suggests that bisphosphonates and bortezomib treatments not
      only inhibit bone destruction, but also reduce the viability of myeloma cells.
      This contributes to the current debate as to whether bisphosphonate therapy has
      an anti-tumour effect. On the other hand, the analyses indicate that treatments
      designed to inhibit TGF-beta do not reduce bone destruction, although it appears
      that they might reduce the viability of myeloma cells, which again contributes to
      the current controversy regarding the efficacy of TGF-beta inhibition in multiple
      myeloma-induced bone disease.

PMID- 26198468
TI  - Erratum to: Tamlana nanhaiensis sp. nov., isolated from surface seawater
      collected from the South China Sea.

PMID- 26198469
TI  - Structures of FolT in substrate-bound and substrate-released conformations reveal
      a gating mechanism for ECF transporters.
AB  - Energy-coupling factor (ECF) transporters are a new family of ABC transporters
      that consist of four subunits, two cytoplasmic ATPases EcfA and EcfA' and two
      transmembrane proteins namely EcfS for substrate-specific binding and EcfT for
      energy coupling. Here, we report the 3.2-A resolution crystal structure of the
      EcfS protein of a folate ECF transporter from Enterococcus faecalis-EfFolT, a
      close homologue of FolT from Lactobacillus brevis-LbFolT. Structural and
      biochemical analyses reveal the residues constituting the folate-binding pocket
      and determining the substrate-binding specificity. Structural comparison of the
      folate-bound EfFolT with the folate-free LbFolT contained in the holotransporter
      complex discloses significant conformational change at the L1 loop, and reveals a
      gating mechanism of ECF transporters in which the L1 loop of EcfS acts as a gate
      in the substrate binding and release. 

PMID- 26198470
TI  - PLR Study Participants Lack the Risk Factors for the Rare Entity Called EDTA
      Dependent Pseudothrombocytopenia.

PMID- 26198471
TI  - Postprandial Glucose Increases the Risk of Coronary Artery Disease.

PMID- 26198472
TI  - Does Epicardial Adipose Tissue Thickness Has an Independent Relationship With
      Infarct-Related Artery Patency?

PMID- 26198473
TI  - Carotid Plaques Correlates in Patients With Familial Hypercholesterolemia.
AB  - Patients with familial hypercholesterolemia (FH) are at increased risk of
      premature cardiovascular disease. We compared factors associated with the
      presence of carotid plaques and carotid intima-media thickness (cIMT), markers of
      subclinical atherosclerosis, in 241 patients with FH (98, 40.7% men; mean age 41
      +/- 18.4 years). Patients with FH having carotid plaques (36.5%) had mean age,
      apolipoprotein (apo) B, glucose, apoA1, systolic blood pressure (SBP) and
      diastolic BP, waist/hip ratio (WHR), and body mass index higher than patients
      without plaques. Logistic regression revealed that apoB (odds ratio [OR] per 1
      unit change 1.03,P= .005), high-density lipoprotein cholesterol (HDL-C; OR per 1
      standard deviation [SD] change 0.59,P= .015), and non-HDL-C (OR per 1SD change
      1.53,P= .04) were significantly associated with the presence of plaques. The cIMT
      correlated with obesity parameters, BP, apoB, glucose, high-sensitivity C
      reactive protein, creatinine, gamma-glutamyl transpeptidase, and alanine
      transaminase (P< .001). Regression analysis revealed that cIMT was significantly
      associated with apoB, SBP, and WHR. These results confirm the role of apoB
      containing lipoproteins and low HDL-C with the presence of carotid plaques and
      apoB, BP, and WHR with cIMT. 

PMID- 26198474
TI  - Mutations in the Gardos channel (KCNN4) are associated with hereditary
      xerocytosis.
AB  - Hereditary xerocytosis (HX; MIM 194380) is an autosomal-dominant hemolytic anemia
      characterized by primary erythrocyte dehydration. In many patients, heterozygous
      mutations associated with delayed channel inactivation have been identified in
      PIEZO1. This report describes patients from 2 well-phenotyped HX kindreds,
      including from one of the first HX kindreds described, who lack predicted
      heterozygous PIEZO1-linked variants. Whole-exome sequencing identified novel,
      heterozygous mutations affecting the Gardos channel, encoded by the KCNN4 gene,
      in both kindreds. Segregation analyses confirmed transmission of the Gardos
      channel mutations with disease phenotype in affected individuals. The KCNN4
      variants were different mutations in the same residue, which is highly conserved
      across species and within members of the small-intermediate family of calcium
      activated potassium channel proteins. Both mutations were predicted to be
      deleterious by mutation effect algorithms. In sickle erythrocytes, the Gardos
      channel is activated under deoxy conditions, leading to cellular dehydration due
      to salt and water loss. The identification of KCNN4 mutations in HX patients
      supports recent studies that indicate it plays a critical role in normal
      erythrocyte deformation in the microcirculation and participates in maintenance
      of erythrocyte volume homeostasis. 

PMID- 26198475
TI  - Impact of Electrode Type on Mapping of Scar-Related VT.
AB  - BACKGROUND: Substrate-based VT ablation is mostly based on maps acquired with
      ablation catheters. We hypothesized that multipolar mapping catheters are more
      effective for identification of scar and local abnormal ventricular activity
      (LAVA). METHODS AND RESULTS: Phase1: In a sheep infarction model (2 months
      postinfarction), substrate mapping and LAVA tagging (CARTO(r) 3) was performed,
      using a Navistar (NAV) versus a PentaRay (PR) catheter (Biosense Webster).
      Phase2: Consecutive VT ablation patients from a single center underwent NAV
      versus PR mapping. Point pairs were defined as a PR and a NAV point located
      within a 3D-distance of <=3 mm. Agreement was defined as both points in a pair
      being manually tagged as normal or LAVA. Four sheep (4 years, 50 +/- 4.8 kg) and
      9 patients were included (53 +/- 14 years, 8 male, 6 ischemic cardiomyopathy).
      Mapping density was higher within the scar with PR versus NAV (3.2 vs. 0.7
      points/cm2 , P = 0.001) with larger bipolar scar area (68 +/- 55 cm2 vs. 58 +/-
      48 cm2 , P = 0.001). In total, 818 point pairs were analyzed. Using PR, far-field
      voltages were smaller (PR vs. NAV; bipolar: 1.43 +/- 1.84 mV vs. 1.64 +/- 2.04
      mV, P = 0.001; unipolar; 4.28 +/- 3.02 mV vs. 4.59 +/- 3.67 mV, P < 0.001). More
      LAVA were also detected with PR (PR vs. NAV; 126 +/- 113 vs. 36 +/- 29, P =
      0.001). When agreement on LAVA was reached (overall: 72%; both LAVA, 40%; both
      normal, 82%) higher LAVA voltages were recorded on PR (0.48 +/- 0.33 mV vs. 0.31
      +/- 0.21 mV, P = 0.0001). CONCLUSION: Multipolar mapping catheters with small
      electrodes provide more accurate and higher density maps, with a higher
      sensitivity to near-field signals. Agreement between PR and NAV is low.

PMID- 26198476
TI  - The potential role of natriuretic peptides and other biomarkers in heart failure
      diagnosis, prognosis and management.
AB  - Heart failure (HF) is a complex disease process that is challenging to diagnose
      and manage. For more than 15 years, biomarkers have been used to diagnose and the
      guide the management of patients with this disease. The gold standard biomarkers
      for HF are B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP);
      both are used for diagnosis and prognosis. More recently, there has been an
      interest in use of BNP and NT-proBNP for HF management as well. Important aspects
      regarding production and clearance of BNP and NT-proBNP exist, which are vital
      for the clinician to understand. Beyond BNP or NT-proBNP, other newer biomarkers
      such as mid-regional pro-atrial natriuretic peptide, soluble ST2, highly
      sensitive troponin and renal biomarkers may add value for prognostication and
      possibly, patient management. In this article, the authors will discuss the
      established and evolving role of BNP and NT-proBNP in HF, along with
      consideration of select newer biomarkers in this setting. 

PMID- 26198478
TI  - Seasonal Variation, Cranial Autonomic Symptoms, and Functional Disability in
      Migraine: A Questionnaire-Based Study in Tertiary Care.
AB  - OBJECTIVE/BACKGROUND: Seasonal variation of migraine attack frequency has been
      described as a phenomenon. We aimed to compare functional disability and the
      occurrence of cranial autonomic symptoms (CASs) in patients who reported a
      seasonal variation in their migraine attack frequency with those who did not.
      METHODS: We conducted a questionnaire-based observational study on patients with
      migraine without aura who visited our institution from January 2005 to December
      2013. Patient demographics, headache characteristics, and accompanying symptoms
      were recorded, and functional disability was evaluated by Migraine Disability
      Assessment (MIDAS) Questionnaire. RESULTS: Of 4423 patients screened, 769 were
      eligible for analysis, and 104 (13.5%) of them reported seasonal variation.
      Several CAS features such as conjunctival injection (25.0% vs 14.0%), lacrimation
      (20.2% vs 10.8%), eyelid edema (20.2% vs 10.2%), forehead and facial sweating
      (22.1% vs 11.4%), and ptosis (23.1% vs 11.4%) were more prominent in this subset
      of patients. They showed higher MIDAS scores (15.4 +/- 23.5) than the other
      migraineurs (10.4 +/- 16.9), with a 1.77-fold increased risk (95% confidence
      interval 1.06-2.96) of severe functional disability (MIDAS score >=21) after
      adjustment for age group, sex, headache frequency, intensity, and duration. The
      higher the number of CASs, the greater also was the proportion of patients with
      severe functional disability. CONCLUSIONS: Patients who reported seasonal
      variation in migraine also reported more CASs and had more severe functional
      disability. The profound functional disability in the migraineurs reporting
      seasonal variation or CAS also provides direction for proactive clinical
      management in these patients.

PMID- 26198477
TI  - Timing of fluoride intake and dental fluorosis on late-erupting permanent teeth.
AB  - OBJECTIVE: Very few studies have examined the relationship between timing of
      fluoride intake and development of dental fluorosis on late-erupting permanent
      teeth using period-specific fluoride intake information. This study examined this
      relationship using longitudinal fluoride intake information from the Iowa
      Fluoride Study. METHODS: Participants' fluoride exposure and intake (birth to 10
      years of age) from water, beverages, selected food products, dietary fluoride
      supplements, and fluoride toothpaste was collected using questionnaires sent to
      parents at 3- and 4- month intervals from birth to 48 months of age and every 6
      months thereafter. Three trained and calibrated examiners used the Fluorosis Risk
      Index (FRI) categories to assess 16 late-erupting teeth among 465 study
      participants. A tooth was defined as having definitive fluorosis if any of the
      zones on that tooth had an FRI score of 2 or 3. Participants with questionable
      fluorosis were excluded from analyses. Descriptive and logistic regression
      analyses were performed to assess the importance of fluoride intake during
      different time periods. RESULTS: Most dental fluorosis in the study population
      was mild, with only four subjects (1%) having severe fluorosis (FRI Score 3). The
      overall prevalence of dental fluorosis was 27.8%. Logistic regression analyses
      showed that fluoride intake from each of the individual years from age 2 to 8
      plays an important role in determining the risk of dental fluorosis for most late
      erupting permanent teeth. The strongest association for fluorosis on the late
      erupting permanent teeth was with fluoride intake during the sixth year of life.
      CONCLUSION: Late-erupting teeth may be susceptible to fluorosis for an extended
      period from about age 2 to 8. Although not as visually prominent as the maxillary
      central incisors, some of the late-erupting teeth are esthetically important and
      this should be taken into consideration when making recommendations about dosing
      of fluoride intake.

PMID- 26198479
TI  - Polyelectrolyte multilayer-assisted fabrication of non-periodic silicon
      nanocolumn substrates for cellular interface applications.
AB  - Recent advances in nanostructure-based biotechnology have resulted in a growing
      demand for vertical nanostructure substrates with elaborate control over the
      nanoscale geometry and a high-throughput preparation. In this work, we report the
      fabrication of non-periodic vertical silicon nanocolumn substrates via
      polyelectrolyte multilayer-enabled randomized nanosphere lithography. Owing to
      layer-by-layer deposited polyelectrolyte adhesives, uniformly-separated
      polystyrene nanospheres were securely attached on large silicon substrates and
      utilized as masks for the subsequent metal-assisted silicon etching in solution.
      Consequently, non-periodic vertical silicon nanocolumn arrays were successfully
      fabricated on a wafer scale, while each nanocolumn geometric factor, such as the
      diameter, height, density, and spatial patterning, could be fully controlled in
      an independent manner. Finally, we demonstrate that our vertical silicon
      nanocolumn substrates support viable cell culture with minimal cell penetration
      and unhindered cell motility due to the blunt nanocolumn morphology. These
      results suggest that vertical silicon nanocolumn substrates may serve as a useful
      cellular interface platform for performing a statistically meaningful number of
      cellular experiments in the fields of biomolecular delivery, stem cell research,
      etc. 

PMID- 26198480
TI  - Role of the nucleotide-binding domain-like receptor protein 3 inflammasome in
      acute kidney injury.
AB  - Acute kidney injury (AKI), which is associated with high mortality rates,
      involves renal inflammation related to the activation of innate immunity. The
      inflammatory response in AKI involves the inflammasome, which integrates danger
      signals into caspase-1-activating platforms, leading to the processing and
      secretion of the proinflammatory cytokines interleukin (IL)-1beta and IL-18. The
      nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome plays a
      role in the development of many diseases, including AKI. However, the mechanisms
      by which the NLRP3 inflammasome translates different danger signals into the
      expression of proinflammatory cytokines remain unclear. Here, we investigated the
      role of the NLRP3 inflammasome in renal injury in a cecal ligation and puncture
      (CLP) model of sepsis-induced AKI. CLP decreased blood pressure and increased
      serum creatinine levels and neutrophil infiltration into the kidney in parallel
      with the upregulation of NLRP3, the adaptor protein apoptosis-associated speck
      like protein, and caspase-1 expression and activity in kidney tissues, and
      increases in the serum and kidney levels of IL-1beta and IL-18. Genetic deletion
      of NLRP3 reversed the CLP-induced reduction in blood pressure and increases in
      serum creatinine level and neutrophil infiltration, and attenuated the CLP
      induced upregulation of apoptosis-associated speck-like protein, caspase-1
      expression and activity, and the secretion of IL-1beta and IL-18, similarly to
      the effects of caspase-1 inhibition. Taken together, our results indicate that
      activation of the NLRP3 inflammasome contributes to the development of
      hypotension and the inflammatory response of AKI, suggesting its possible role as
      a therapeutic target for the treatment of kidney diseases. 

PMID- 26198481
TI  - Investigation on critical structural motifs of ligands for triggering
      glucocorticoid receptor nuclear migration through molecular docking simulations.
AB  - The glucocorticoid receptor (GR), a transcription factor regulating gene
      expression in a ligand-dependent fashion, is known for flexibility in adapting
      various ligands with their structures ranging from steroid to non-steroid.
      However, in our previous study, GR shows a stringent discrimination against a set
      of steroid ligands with highly similar structures for triggering its nuclear
      migration. In order to resolve this puzzle, we employed molecular docking
      simulations to investigate the origin of this structural discrimination. By
      analyzing the docking orientations and the related ligand-GR interaction
      patterns, we found that the hydrophilicity mismatch between the docking ligand
      and the GR ligand-binding site is the main cause combined with the steric
      hindrance and structural rigidness of these steroid ligands. Furthermore, we
      utilized this knowledge to rationalize how the structure-binding interaction of
      non-steroid ligands triggers GR nuclear migration with their structures available
      in Protein Data Bank. 

PMID- 26198482
TI  - Want weekend working Mr Hunt? Then pay for it.
AB  - I loved the #ImInWorkJeremy Twitter response to the health secretary's ultimatum
      last week over moving to a seven-day NHS by 2020. Health staff posted selfies of
      themselves at work over the weekend to make the point that for many front line
      NHS professionals, weekend working is already the norm. 

PMID- 26198483
TI  - Seven-day working will hit nurses in the pocket, says NHS pay body.
AB  - The introduction of a full seven-day NHS service could result in reduced total
      earnings for nurses and midwives, leaving staff unprepared to work unsocial
      hours, the independent NHS Pay Review Body (RB) has said. 

PMID- 26198484
TI  - Hospitals' avoidable death figures to be published in a world first.
AB  - The number of avoidable deaths at every hospital will be published from March
      next year. 

PMID- 26198485
TI  - Mealtime support and standards of dignity patchy, but improving.
AB  - Poor or patchy standards of patient dignity and support with eating were too
      common in the 'vast majority' of English hospitals, according to a report. 

PMID- 26198486
TI  - Nurse's Ebola work wins praise of PM.
AB  - A military nurse who became the first patient to receive an experimental Ebola
      drug has received a special medal for her services. 

PMID- 26198487
TI  - 'Revalidation flaws could put registrations at risk'.
AB  - The RCN is appealing to the nurse regulator not to rush into revalidation because
      it risks an exodus from the register if glitches in the new system are not
      resolved. 

PMID- 26198488
TI  - Report on neglect sparks FtP hearings.
AB  - A major review of neglect of older people has led to three nurses being removed
      from the register and a further six being involved in fitness to practise
      hearings, the Nursing and Midwifery Council said. 

PMID- 26198491
TI  - The benefits of pre-degree work experience analysed.
AB  - An analysis is under way into the benefits of gaining healthcare work experience
      before starting nurse training. 

PMID- 26198489
TI  - Academy calls for safe staffing in all professions.
AB  - NHS boards and the government in Scotland should develop minimum safe staffing
      levels, a report states. 

PMID- 26198492
TI  - Flexibility is key to nurse retention.
AB  - Flexible employment options should be introduced by employers to boost retention
      and tackle staff shortages, says England's chief nurse. 

PMID- 26198493
TI  - NICE to cast independent eye over chief nurse's safe staffing guidance.
AB  - The National Institute for Health and Care Excellence will independently review
      safe staffing guidance developed by England's chief nurse Jane Cummings, the
      health secretary said last week. 

PMID- 26198494
TI  - Study questions effectiveness of mortality indicators.
AB  - Standardised mortality ratios for hospitals do not provide an accurate picture of
      how many deaths could have been avoided, according to a study. 

PMID- 26198495
TI  - Nursing staff fighting to balance the cost of living.
AB  - Chancellor George Osborne's announcement of a public sector pay cap until 2020
      will have left nurses worried about how to make their salaries stretch even
      further than they do already. 

PMID- 26198501
TI  - Suspected cancer.

PMID- 26198502
TI  - Conscious of deterioration.
AB  - Nurse consultant Gillian Robinson developed a coma assessment tool that has
      helped to radically improve the safety of care provided to neonates, infants,
      children and young people. Crucially, the tool is tailored to specific age
      groups. Ms Robinson's achievement was recognised earlier this year when she won
      the child health category in this year's Nursing Standard Nurse Awards.

PMID- 26198503
TI  - RCNi.com--have you joined us yet?
AB  - In March we launched our website www.rcni.com . Since then, more than 27,500 of
      you have signed up to the site, many to prepare for revalidation by using the
      RCNi Portfolio, others to stay informed using our daily nursing news updates, in
      depth features and clinical articles. We are delighted the response so far has
      been incredibly positive. 

PMID- 26198504
TI  - The long road to recovery.
AB  - Nearly 80,000 people in the UK today were diagnosed with cancer when they were
      under the age of 45. Younger people with cancer face particular pressures, as the
      disease coincides with the peak years for raising a family and forging a career.
      Macmillan Cancer Support has developed a package of interventions to improve
      outcomes for people in this group.

PMID- 26198518
TI  - Academic bodies have no business meddling in fees.

PMID- 26198519
TI  - Consider the effect on patients of all those equipment alarms.

PMID- 26198517
TI  - End of life care can be complex, but it is essential we get it right.
AB  - According to a recent survey on end of life care, around one in seven bereaved
      people felt their loved one did not have their nutrition or hydration needs met
      in the last two days of life (news July 15).

PMID- 26198521
TI  - Oh for a culture where mistakes are not treated as criminal.

PMID- 26198523
TI  - Tuition fees will create risk and imperil seven-day care.

PMID- 26198524
TI  - Helen Coupland 1920-2015.
AB  - Practice nurse Helen Coupland (nee Irons) was born in the Rhondda Valley in South
      Wales, and shared a happy childhood there with her younger brother, Ted. At 17
      she became a nursing student at Llwynypia Hospital, Pontypridd, where she
      excelled in her studies and found her calling. 

PMID- 26198525
TI  - Elizabeth (Betty) Raybould OBE 1926-2015.
AB  - After working as a post office clerk and volunteering with the Air Raid
      Precautions, Betty Raybould started her nurse training at Central Middlesex
      Hospital in 1945. 

PMID- 26198527
TI  - Diagnosis and support for younger people with dementia.
AB  - There is a lack of recognition by staff working in healthcare and social services
      that people under the age of 65 can develop dementia, according to families
      affected by early onset of the condition. This results in a substantial delay in
      referral and diagnosis, which can lead to significant family and relationship
      difficulties. There is also a lack of specialist advice and support after a
      diagnosis of young-onset dementia, which adds to feelings of distress and
      isolation for both the person and their family. This article, which is part of a
      series on dementia, explores the epidemiology of young-onset dementia as well as
      the assessment, diagnosis and support for younger people living with dementia. It
      emphasises the need for specialist services and outlines the nurse's role in
      supporting families living with the effects of young-onset dementia. 

PMID- 26198528
TI  - Rigour in quantitative research.
AB  - This article which forms part of the research series addresses scientific rigour
      in quantitative research. It explores the basis and use of quantitative research
      and the nature of scientific rigour. It examines how the reader may determine
      whether quantitative research results are accurate, the questions that should be
      asked to determine accuracy and the checklists that may be used in this process.
      Quantitative research has advantages in nursing, since it can provide numerical
      data to help answer questions encountered in everyday practice. 

PMID- 26198529
TI  - Improving nutrition in older people in acute care.
AB  - Older people have an increased risk of becoming malnourished when they are ill.
      Admission to hospital may affect their nutritional intake and nutritional status.
      Nutrition screening and implementation of nutrition care plans can help minimise
      the risk of malnutrition in acute care settings, if used effectively. The
      nutritional care provided to older inpatients should be timely, co-ordinated,
      reviewed regularly and communicated effectively between healthcare professionals
      and across shifts. This article explores what malnutrition means, why older
      people in hospital might be at risk of malnutrition and the effect hospital
      admission might have on nutrition and fluid intake. It makes suggestions for
      addressing these issues, encourages nurses to look at the nutritional care
      provided in their clinical area, to reflect on what they do well and consider
      what can be done to improve patients' experiences. 

PMID- 26198530
TI  - Medication errors.
AB  - Reading the CPD article helped me to understand the many different patient
      factors that contribute to the risk of medication errors, including multiple
      medication use, poor communication, passive involvement and complicated drug
      calculations. 

PMID- 26198531
TI  - Work in progress.
AB  - Nursing roles have changed substantially in the past decade due to technological
      advances, and the NHS Five Year Forward View suggests there will be more
      developments within the health service in the near future. 

PMID- 26198533
TI  - Making the most of complaints.
AB  - Dealing with complaints from patients can be challenging. But for practice nurse
      Cherilee Angland, the process reminds her not to be complacent about care. 

PMID- 26198534
TI  - Get it right from the start.
AB  - With graduation day over and their names and PIN numbers appearing on the Nursing
      and Midwifery Council register, newly qualified nurses will soon be starting
      their first jobs. 

PMID- 26198535
TI  - Student life--the heart of learning.
AB  - The University of Nottingham introduced a new undergraduate nursing degree
      programme in 2012 that aims to develop nurses who are resilient, innovative, able
      to empower service users and provide compassionate care. 

PMID- 26198536
TI  - Characterization of a novel HLA-B allele (HLA-B*18:108) by intron-exon sequencing
      of the HLA-B locus.
AB  - HLA-B*18:108 has two nucleotide changes from B*18:01:01:02 at nt 430 where A -> G
      and nt 431 where G -> A. 

PMID- 26198538
TI  - Erratum to: Influence of diffusion on the stability of equilibria in a reaction
      diffusion system modeling cholera dynamic.

PMID- 26198539
TI  - Fish-seastar facilitation leads to algal forest restoration on protected rocky
      reefs.
AB  - Although protected areas can lead to recovery of overharvested species, it is
      much less clear whether the return of certain predator species or a diversity of
      predator species can lead to re-establishment of important top-down forces that
      regulate whole ecosystems. Here we report that the algal recovery in a
      Mediterranean Marine Protected Area did not derive from the increase in the
      traditional strong predators, but rather from the establishment of a previously
      unknown interaction between the thermophilic fish Thalassoma pavo and the seastar
      Marthasterias glacialis. The interaction resulted in elevated predation rates on
      sea urchins responsible for algal overgrazing. Manipulative experiments and field
      observations revealed that the proximity of the seastars triggered an escape
      response in sea urchins, extending their tube feet. Fishes exploited this
      behavior by feeding on the exposed tube feet, thus impairing urchin movement, and
      making them vulnerable to predation by the seastars. These findings suggest that
      predator diversity generated by MPA establishment can activate positive
      interactions among predators, with subsequent restoration of the ecosystem
      structure and function through cascading consumer impacts. 

PMID- 26198540
TI  - An olive-shaped SnO2 nanocrystal-based low concentration H2S gas sensor with high
      sensitivity and selectivity.
AB  - Olive-shaped SnO2 nanocrystals were synthesized successfully via a facile
      hydrothermal route, using tin dichloride hydrate, oxalic acid dihydrate and
      polyvinylpyrrolidone as reaction precursors, and showed great potential in the
      large-scale preparation of SnO2 nanocrystals. The prepared SnO2 nanocrystals were
      characterized using XRD, XPS, SEM, TEM and HRTEM, and showed well-defined olive
      shaped tetragonal single-crystals with irregular exposed facets. The growth
      mechanism of the olive-shaped SnO2 nanocrystals was considered after
      investigating the experimental conditions and reaction time. Due to the abundant
      active sites on the irregular surfaces, the gas sensing performance of the
      prepared SnO2 nanocrystals exhibited great gas sensing properties, including high
      sensitivity, selectivity and stability towards H2S with a very low detection
      limit (less than 0.5 ppm), revealing their great potential in commercial
      applications for H2S gas detection. 

PMID- 26198537
TI  - Development of a multiparameter flow cytometric assay as a potential biomarker
      for homologous recombination deficiency in women with high-grade serous ovarian
      cancer.
AB  - OBJECTIVES: PARP inhibitors (PARPi) are a novel class of drugs with activity in
      patients with acquired or germline homologous recombination (HR) deficiency
      associated high-grade serous ovarian cancer (HGSOC). We hypothesized that
      measuring gammaH2AX as an indicator of DNA double-strand breaks (DSB), and MRE11
      or RAD51 as an indicator of DSB repair, would reflect HR status and predict
      response to PARPi-based therapy. Our aim was to develop and use high-throughput
      multiparametric flow cytometry to quantify gammaH2AX with MRE11 or RAD51 in PBMCs
      as a readily available surrogate. METHODS: Healthy donor PBMCs were used for
      assay development and optimization. We validated induction of gammaH2AX, MRE11
      and RAD51 by staining with fluorophore-conjugated antibodies. The multiparameter
      flow cytometric method was applied to PBMC samples from recurrent HGSOC patients
      who were treated with PARPi, olaparib and carboplatin. RESULTS: Stimulation was
      necessary for quantification of a DNA damage response to olaparib/carboplatin in
      healthy donor PBMCs. The flow cytometric protocol could not distinguish between
      cytoplasmic and nuclear RAD51, erroneously indicating activation in response to
      injury. Thus, MRE11 was selected as the marker of DSB repair. PBMCs from 15
      recurrent HGSOC patients were then examined. Patients who did not respond to
      PARPi therapy had a significantly higher pre-treatment level of gammaH2AX (p =
      0.01), and a higher ratio of gammaH2AX/MRE11 (11.0 [3.5-13.2] v. 3.3 [2.8-9.9], p
      < 0.03) compared with responders. CONCLUSIONS: We successfully developed and
      applied a multiparameter flow cytometry assay to measure gammaH2AX and MRE11 in
      PBMCs. Prospective studies will be required to validate this surrogate biomarker
      assay as a potential predictive biomarker of PARPi-based therapy.

PMID- 26198541
TI  - Role of community pharmacists in the detection of potentially inappropriate
      benzodiazepines prescriptions for insomnia.
AB  - BACKGROUND: The appropriate management of chronic insomnia is crucial and
      prescribing of hypnotic drugs is common. Regular and prolonged use of hypnotics
      should be avoided because of the risk of tolerance to effects, dependence and an
      increased risk of adverse events. In 2012, updated Beers criteria for potentially
      inappropriate medication in older adults suggested to avoid all benzodiazepines
      in older adults to treat insomnia. In addition, successful discontinuation may
      result in improvements on cognitive and psychomotor function, particularly in
      older people. OBJECTIVE: To investigate the appropriateness of benzodiazepines
      prescription for insomnia and explore the role that community pharmacists can
      have in identifying signals of potential inappropriate drug prescriptions.
      SETTING: Community pharmacies in Italy. METHOD: This is an observational study
      conducted in 8 community pharmacies. Each pharmacist was asked to interview a
      sample of patients with the prescriptions of at least one benzodiazepine and to
      complete a minimum data set collecting information about socio-demographic
      characteristics, drug indication, duration of drug prescription, number of
      hypnotic-drugs, previous attempt to drug-discontinuation, preference of patients
      about benzodiazepine withdrawal and modality of drug tapering. Main outcome
      measure Indications, treatment duration, dosage and drug discontinuation attempts
      and modalities. RESULTS: A total of 181 participants were interviewed. About half
      of respondents (n = 81) reported to be treated for insomnia and 62 % were elderly
      (mean age 68, range 27-93). Fifty-two patients (64 %) were on long term treatment
      (>3 years) while for thirteen patients (16 %) duration of treatment was comprised
      between 1 and 3 years. Thirty-three patients were in favour of benzodiazepine
      discontinuation but in all cases discontinuation was unsuccessful. CONCLUSION:
      Use of community pharmacy survey data allowed us to obtain information about
      incorrect management of insomnia and inappropriate benzodiazepines prescriptions.
      Stricter adherence to evidence-based guidelines is essential for a rational use
      of hypnotic and sedatives.

PMID- 26198542
TI  - Early childhood caries in Switzerland: a marker of social inequalities.
AB  - BACKGROUND: Early childhood caries (ECC) is a marker of social inequalities
      worldwide because disadvantaged children are more likely to develop caries than
      their peers. This study aimed to define the ECC prevalence among children living
      in French-speaking Switzerland, where data on this topic were scarce, and to
      assess whether ECC was an early marker of social inequalities in this country.
      METHODS: The study took place between 2010 and 2012 in the primary care facility
      of Lausanne Children's Hospital. We clinically screened 856 children from 36 to
      71 months old for ECC, and their caregivers (parents or legal guardians) filled
      in a questionnaire including items on socioeconomic background (education,
      occupation, income, literacy and immigration status), dental care and dietary
      habits. Prevalence rates, prevalence ratios and logistic regressions were
      calculated. RESULTS: The overall ECC prevalence was 24.8 %. ECC was less frequent
      among children from higher socioeconomic backgrounds than children from lower
      ones (prevalence ratios <= 0.58). CONCLUSIONS: This study reported a worrying
      prevalence rate of ECC among children from 36 to 71 months old, living in French
      speaking Switzerland. ECC appears to be a good marker of social inequalities as
      disadvantaged children, whether from Swiss or immigrant backgrounds, were more
      likely to have caries than their less disadvantaged peers. Specific preventive
      interventions regarding ECC are needed for all disadvantaged children, whether
      immigrants or Swiss.

PMID- 26198543
TI  - Magnetically tunable broadband transmission through a single small aperture.
AB  - Extraordinary transmission through a small aperture is of great interest.
      However, it faces a limitation that most of approaches can not realize the
      tunable transmission property, which is not benefit for the miniaturization of
      the microwave system. Here, we demonstrate a magnetically tunable broadband
      transmission through a small aperture. By placing two ferrite rods symmetrically
      on both sides of a single small aperture, the strongly localized electromagnetic
      fields are effectively coupled to the two ferrite rods. Both the simulated and
      experimental results indicate that such structure not only realizes a nearly
      total transmission through a small aperture, but also obtains a magnetically
      tunable property. This work offers new opportunities for the miniaturization of
      the microwave system. 

PMID- 26198544
TI  - Asymmetry in Time Evolution of Magnetization in Magnetic Nanostructures.
AB  - Strong interest in nanomagnetism stems from the promise of high storage densities
      of information through control of ever smaller and smaller ensembles of spins.
      There is a broad consensus that the Landau-Lifshitz-Gilbert equation reliably
      describes the magnetization dynamics on classical phenomenological level. On the
      other hand, it is not so evident that the magnetization dynamics governed by this
      equation contains built-in asymmetry in the case of broad topology sets of
      symmetric total energy functional surfaces. The magnetization dynamics in such
      cases shows preference for one particular state from many energetically
      equivalent available minima. We demonstrate this behavior on a simple one-spin
      model which can be treated analytically. Depending on the ferromagnet geometry
      and material parameters, this asymmetric behavior can be robust enough to survive
      even at high temperatures opening simplified venues for controlling magnetic
      states of nanodevices in practical applications. Using micromagnetic simulations
      we demonstrate the asymmetry in magnetization dynamics in a real system with
      reduced symmetry such as Pacman-like nanodot. Exploiting the built-in asymmetry
      in the dynamics could lead to practical methods of preparing desired spin
      configurations on nanoscale. 

PMID- 26198545
TI  - Influence of patient medication information format on comprehension and
      application of medication information: A randomized, controlled experiment.
AB  - OBJECTIVE: To examine patients' comprehension and application of alternative
      versions of patient medication information handouts for a fictitious drug, and
      whether patient characteristics influence patients' ability to understand the
      handouts. METHODS: A web-based experiment was conducted in which 1397 adults with
      rheumatoid arthritis, ankylosing spondylitis, or plaque psoriasis were randomly
      assigned to one of three conditions: (1) a one-page "Bubbles" format; (2) a one
      page "Over-The-Counter" (OTC) format; and (3) a four-page document modeled after
      MedGuides used in 2009 which served as the control arm. Comprehension and
      application of information in the handouts were the key outcomes of interest.
      RESULTS: Participants who viewed either the Bubbles or OTC formats had greater
      comprehension than participants who viewed the MedGuide, but did not have better
      application scores. No significant differences were noted between the Bubbles and
      OTC formats. Patient characteristics did not moderate the results. CONCLUSION:
      Both formats resulted in better comprehension than the MedGuide format used in
      the study. PRACTICE IMPLICATIONS: Results provide valuable information on how to
      design patient information to improve patients' understanding of the risks and
      benefits of the drugs they are prescribed. Results could be extended to inform
      the content of other types of patient education materials.

PMID- 26198546
TI  - Low health literacy associated with higher medication costs in patients with type
      2 diabetes mellitus: Evidence from matched survey and health insurance data.
AB  - OBJECTIVE: Studies have shown that people with lower levels of health literacy
      create higher emergency, inpatient and total healthcare costs, yet little is
      known about how health literacy may affect medication costs. This cross-sectional
      study aims at investigating the relationship between health literacy and three
      years of medication costs (2009-2011) in a sample of patients with type 2
      diabetes. METHODS: 391 patients from the German-speaking part of Switzerland who
      were insured with the same health insurer were interviewed. Health literacy was
      measured by a validated screening question and interview records were
      subsequently matched with data on medication costs. A bootstrap regression
      analysis was applied to investigate the relationship between health literacy and
      medication costs. RESULTS: In 2010 and 2011 lower levels of health literacy were
      significantly associated with higher medication costs (p<.05). CONCLUSION: The
      results suggest that diabetic patients with lower health literacy will create
      higher medication costs. PRACTICE IMPLICATIONS: Besides being sensitive towards
      patients' health literacy levels, healthcare providers may have to take into
      account its potential impact on patients' medication regimen, misuse and
      healthcare costs.

PMID- 26198547
TI  - Experimental determination of multiple thermodynamic and kinetic risk factors for
      nephrolithiasis in the urine of healthy controls and calcium oxalate stone
      formers: does a universal discriminator exist?
AB  - Nephrolithiasis is thought to be governed by urinary thermodynamic and kinetic
      risk factors. However, identification of one or more of these factors which
      consistently and unambiguously differentiates between healthy subjects (N) and
      calcium oxalate (CaOx) renal stone patients (SF) remains elusive. The present
      study addresses this challenge. 24 h urines were collected from 15 N and 10 SF.
      Urine compositions were used to compute thermodynamic risk indices including
      urinary ratios, quotients and supersaturation (SS) values, while CaOx metastable
      limits (MSL) were determined experimentally. Crystallisation kinetics was
      determined by measuring rates of particle formation (number, volume, size) using
      a Coulter counter multisizer (CC) and a Coulter flow cytometer (FC). Particle
      shapes were qualitatively differentiated by FC and were viewed directly by
      scanning electron microscopy. Several urinary composition ratios and risk
      quotients were significantly different between the groups. However, there were no
      significant differences between CaOx MSL or SS values. Using transformed FC data,
      the rate of CaOx crystallisation in SF was significantly greater than in N. This
      was not supported by CC measurements. There were no significant differences
      between the groups with respect to particle size or CaOx crystal growth rates.
      Single and aggregated CaOx dihydrate crystals were observed in both groups with
      equal frequency and there were no differences in the kinetic properties of these
      deposits. A few CaOx monohydrate crystals were observed in SF. Although several
      risk factors were found to be significantly different between the groups, none of
      them were consistently robust when compared to other cognate factors. Arguments
      were readily invoked which demonstrated inter-factor inconsistencies and
      conflicts. We suspect that a unique discriminatory factor, such as any of those
      which we investigated in the present study, may not exist. 

PMID- 26198548
TI  - Quality of life after different procedures for regional control in oral cancer
      patients: cross-sectional survey.
AB  - OBJECTIVES: To examine health utilities in patients with cT1-2 oral cavity
      squamous cell carcinoma following different diagnostic and treatment modalities
      for the neck and to investigate the relation between shoulder morbidity and
      health utility. DESIGN: Cross-sectional survey. SETTING: Two Dutch hospitals.
      PARTICIPANTS: Four subgroups of patients with oral cavity cancer who underwent
      watchful waiting, sentinel lymph node biopsy, elective supraomohyoid neck
      dissection or therapeutic modified radical neck dissection. MAIN OUTCOME
      MEASURES: Patients received the EuroQol-5D-3L questionnaire and the shoulder
      disability questionnaire. Mean health utility, visual analogue scale and shoulder
      disability scores were calculated. RESULTS: A total of 181 patients (62%)
      returned the questionnaires. Mean health utilities, adjusted for age, gender and
      time since treatment were 0.804, 0.863, 0.834 and 0.794 for the watchful waiting,
      sentinel lymph node biopsy, supraomohyoid neck dissection and modified radical
      neck dissection subgroups, respectively. Mean shoulder disability scores (higher
      score means more shoulder complaints) for these subgroups were 8.64, 10.57, 18.92
      and 33.66. Patients with shoulder complaints had a mean utility of 0.78 while
      patients without shoulder complaints had a mean utility of 0.90. CONCLUSIONS:
      This study shows that more invasive procedures appear to result in lower health
      utility. The high health utility for patients after sentinel lymph node biopsy
      supports a role for this procedure in patients with oral cancer.

PMID- 26198549
TI  - Trichomonosis in Eurasian sparrowhawks in the Czech Republic.
AB  - Pigeon, doves and songbirds are hosts of the parasite Trichomonas gallinae
      (Rivolta, 1878), which causes avian trichomonosis. Raptors are infected when they
      digest infected prey. A high percentage of the diet of Eurasian sparrowhawk
      Accipiter nisus (Linnaeus) is comprised of birds. During the breeding season 2012
      and 2013, we clinically tested 298 nestling Eurasian sparrowhawks from urban and
      rural areas of the Czech Republic for the presence of trichomonads. Sparrowhawk
      nestlings in the urban area were more infected (32.9%) than in the rural area
      (12.2%) in 2012 (chi(2) = 6.184, P = 0.045). The number of infected nestlings
      dropped in the urban area (5.4%) and remained similar in the rural area (16.6%)
      in 2013. Sequences of ITS region and SSU rDNA confirmed that the isolates from
      infected sparrowhawk nestlings belonged to Trichomonas gallinae. 

PMID- 26198550
TI  - Biofilm: it is time for consensus.

PMID- 26198551
TI  - Effects of lipo-prostaglandin E1 on wound bed microcirculation.
AB  - OBJECTIVE: Lipo-prostaglandin E1 (lipo-PGE1) is a well-known potent vasodilator
      that increases peripheral blood flow. However, the effects of this agent on wound
      bed microcirculation still remain unclear. The present study aims to improve the
      experimental model which our group developed to visualise wound bed
      microcirculation and to evaluate acute stimulation by lipo-PGE1. METHOD: The
      superficial stratum of the Wistar rat's ear skin was microsurgically excised
      preserving the subdermal vascular plexus. The preserved vessels, the wound bed
      microcirculation, were visualised under an intravital microscope-video-computer
      system. Animals were divided into three groups, a control group in which animals
      received vehicle control, a medium-dose group (6 MUg/2 ml/kg lipo-PGE1) and a
      high-dose group (10 MUg/2 ml/kg lipo-PGE1). The blood velocity and diameter of
      individual venules were measured from the recorded microcirculatory images, and
      the blood flow of the venule in the wound bed was evaluated. RESULTS: A
      significant increase in the wound bed blood flow was seen 10 minutes after lipo
      PGE1 injection (p<0.05). This was approximately fourfold the baseline values. The
      increase was greatest in the medium-dose group. Extravasation and accumulation of
      lipo-PGE1 in the wound bed was observed. CONCLUSION: Lipo-PGE1 effectively
      increased wound bed microcirculation blood flow at the optimal dose. DECLARATION
      OF INTEREST: There is no conflict of interest.

PMID- 26198552
TI  - Clinical outcomes and cost-effectiveness of three alternative compression systems
      used in the management of venous leg ulcers.
AB  - OBJECTIVE: To assess clinical outcomes and cost-effectiveness of using a two
      layer cohesive compression bandage (TLCCB; Coban 2) compared with a two-layer
      compression system (TLCS; Ktwo) and a four-layer compression system (FLCS;
      Profore) in treating venous leg ulcers (VLUs) in clinical practice in the UK,
      from the perspective of the National Health Service (NHS). METHOD: This was a
      retrospective analysis of the case records of VLU patients, randomly extracted
      from The Health Improvement Network (THIN) database (a nationally representative
      database of clinical practice among patients registered with general
      practitioners in the UK), who were treated with either TLCCB (n=250), TLCS
      (n=250) or FLCS (n=175). Clinical outcomes and health-care resource use (and
      costs) over six months after starting treatment with each compression system were
      estimated. Differences in outcomes and resource use between treatments were
      adjusted for differences in baseline covariates. RESULTS: Patients' mean age was
      75 years old and 57% were female. The mean time with a VLU was 6-7 months and the
      mean initial wound size was 77-85 cm2. The overall VLU healing rate, irrespective
      of bandage type, was 44% over the six months' study period. In the TLCCB group,
      51% of wounds had healed by six months compared with 40% (p=0.03) and 28%
      (p=0.001) in the TLCS and FLCS groups, respectively. The mean time to healing was
      2.5 months. Patients in the TLCCB group experienced better health-related quality
      of life (HRQoL) over six months (0.374 quality-adjusted life years (QALYs) per
      patient), compared with the TLCS (0.368 QALYs per patient) and FLCS (0.353 QALYs
      per patient). The mean six-monthly NHS management cost was L2,413, L2,707 and
      L2,648 per patient in the TLCCB, TLCS and FLCS groups, respectively. CONCLUSION:
      Despite the systems studied reporting similar compression levels when tested in
      controlled studies, real-world evidence demonstrates that initiating treatment
      with TLCCB, compared with the other two compression systems, affords a more cost
      effective use of NHS-funded resources in clinical practice, since it resulted in
      an increased healing rate, better HRQoL and a reduction in NHS management cost.
      The evidence also highlighted the lack of continuity between clinicians managing
      a wound, the inconsistent nature of the administered treatments and the lack of
      specialist involvement, all of which may impact on healing. DECLARATION OF
      INTEREST: This study was supported by an unrestricted research grant from 3M
      Health Care, UK. 3M Health Care had no influence on the study design, the
      collection, analysis, and interpretation of data, or on the writing of, and
      decision to submit for publication, the manuscript.

PMID- 26198553
TI  - A collaborative project to enhance efficiency through dressing change practice.
AB  - OBJECTIVE: A collaborative project between Hull CHCP and Smith and Nephew wound
      management, which sought to enhance practice efficiency, specifically in relation
      to the optimisation of dressing change frequency. The project involved the use of
      a new foam dressing (Allevyn Life, Smith & Nephew, Hull) designed to manage wound
      exudate more effectively, be more acceptable to patients by masking staining of
      the dressing surface, and to provide both the patient and clinical staff with an
      indicator for dressing change. METHOD: The project comprised a targeted programme
      of training and education to promote appropriate use of the new product and
      encourage practice change in dressing change frequency. The frequency of nursing
      visits, dressing changes and, where applicable, the reasons for a dressing change
      were documented pre- and post-implementation to determine the effect of this
      approach. RESULTS: Switching to the new dressing was accompanied by a reduction
      in dressing change visit frequency in 97.3% (36/37) of patients. The mean
      reduction in dressing change frequency was 1.8 visits per week, representing a
      50.0% reduction. Post-implementation the mean number of dressings used per
      patient per dressing change had fallen from 2.1 at baseline to 1.1 (a 47.6%
      reduction). Furthermore, at baseline an average of 9.8 dressings were used per
      week per patient. This fell to an average of 2.0 dressings per week per patient
      following implementation, a reduction in dressings per patient of 79.6%.
      CONCLUSION: The results illustrate that a much less complex approach to the use
      of dressing products can be achieved. Furthermore, they demonstrate that with the
      adoption of advanced practice-enhancing products, coupled with appropriate
      training, education and effective promotion of practice change, valuable nursing
      time can be released. DECLARATION OF INTEREST: Alistair Bielby is a contractor
      for Smith & Nephew. Richard Searle is an employee of Smith & Nephew. This project
      was supported by an unrestricted grant from Smith & Nephew.

PMID- 26198554
TI  - Positioning bedridden patients to reduce interface pressures over the sacrum and
      great trochanter.
AB  - OBJECTIVE: In this study, we evaluated the effect of hip-joint rotation on the
      interface pressure over the sacrum and greater trochanter with a new protocol for
      positioning of bedridden elderly patients. METHOD: The interface pressure values
      over the sacrum and greater trochanter in bedridden patients were evaluated.
      These were collected in the supine position, 90 degrees  lateral position, and 30
      degrees  and 40 degrees  laterally inclined positions with external rotation or
      neutral positioning of the hip joint. Each interface pressure was assessed with a
      device measuring pressure distribution, after which, the peak pressure index
      (PPI) was calculated. RESULTS: In the 17 patients examined, the PPI over the
      sacrum in the supine position was significantly greater than that in other
      positions. In the 30 degrees  and 40 degrees  laterally inclined positions, the
      PPIs over the greater trochanter were significantly lower in the neutral position
      of the hip joint compared with those in the external rotation position.
      CONCLUSION: Our findings revealed the effects of hip-joint rotation on the
      interface pressure for the greater trochanter, possibly due to the increased
      distance between the greater trochanter and the sacrum caused by neutral position
      of the hip joint. The results demonstrate that it is to best place the hip joint
      in a neutral position when the legs are in contact with the bed in order to
      distribute the pressure over the greater trochanter in the 30 degrees  and 40
      degrees  laterally inclined positions. These results can be applied to the
      clinical setting to improve patient positioning and decrease pressure ulcers.
      DECLARATION OF INTEREST: The authors declare that they have no competing
      financial interests.

PMID- 26198555
TI  - Hydrogel-impregnated dressings for graft fixation: a case series.
AB  - OBJECTIVE: Infection is the second most common cause of graft loss after skin
      grafting. Cutimed Sorbact is a range of dressings coated with a hydrophobic fatty
      acid that irreversibly binds to the bacterial surface and mechanically removes
      bacteria from the wound. The dressing is a hydrogel-impregnated material, which
      prevents wounds from drying. Here, we report on cases in which we used the gel
      instead of the widely used petrolatum gauze or paraffin gauze in a tie-over
      dressing for the fixation of grafted skin. METHOD: Patients treated for skin
      grafting between March 2013 and July 2013 were treated with the hydrogel
      impregnated dressings and a tie over dressing. The wounds were opened five days
      after treatment. RESULTS: In total seven patients were treated with an age range
      of 23-86 years old. No infections were seen and the method was effective
      regardless of wound size, the thickness of the skin harvested and condition of
      the defect. CONCLUSION: Using this hydrogel-impregnated dressings, provide
      antibacterial and moisturising effects simultaneously, which a petrolatum or
      paraffin gauze cannot provide. DECLARATION OF INTEREST: There were no external
      sources of funding for this study. The authors have no conflicts of interest to
      declare.

PMID- 26198556
TI  - Natriuretic Peptides and the Management of Heart Failure.
AB  - Natriuretic peptide has been validated as a useful biomarker in the diagnosis of
      heart failure, although its role in guiding medical management of heart failure
      is not well established. We endeavored to determine if natriuretic peptide-guided
      therapy is associated with improved outcomes for heart failure patients. A total
      of 11 trials (2628 patients) comparing natriuretic peptide-guided therapy with
      standard therapy for heart failure patients were identified; follow-up times
      ranged from 3 months to 3 years. Our data indicate that natriuretic peptide
      levels and all-cause mortality rates do not appear to benefit from natriuretic
      peptide-guided therapy when compared with standard therapy. However, a decreased
      rate of cardiovascular events does appear to be associated with natriuretic
      peptide-guided therapy. 

PMID- 26198557
TI  - Management of Patients With Stable Angina and Type 2 Diabetes.
AB  - Type 2 diabetes (T2D) is a well-established risk factor for patients with
      coronary artery disease (CAD). Patients with CAD and comorbid T2D also have a
      higher risk of cardiovascular complications, such as silent ischemia and stable
      angina. In treating the symptoms of stable angina in patients with CAD and
      comorbid T2D, it is vital to utilize therapies that reduce symptoms and improve
      outcomes. At the same time, there is significant concern about the preservation
      of glycometabolic parameters, such as glycosylated hemoglobin (HbA1c),
      particularly because some antianginal therapies, such as beta-blockers and
      calcium channel blockers-although effective at improving the symptoms of stable
      angina and reducing ischemia-may also worsen glycemic control by increasing HbA1c
      levels. Available trial data on the efficacy of antianginal agents in patients
      with stable angina and comorbid T2D are limited. Therefore, in patients with
      stable angina and T2D, a tailored approach to treatment of stable angina by
      selecting therapies with a neutral or positive glycometabolic profile may improve
      outcomes and increase treatment compliance. Additionally, patients with a dual
      diagnosis may benefit from therapies that have beneficial effects on both stable
      angina and T2D, thereby reducing polypharmacy. Prospective studies in patients
      with stable angina and T2D are needed to guide therapy decisions. 

PMID- 26198558
TI  - Renal Denervation: Past, Present, and Future.
AB  - Hypertension remains a leading cause of cardiovascular morbidity and mortality
      worldwide. It is estimated that 12.8% of hypertensive adults have resistant
      hypertension. The sympathetic nervous system is a well-known contributor to the
      pathophysiology of resistant hypertension. Renal denervation has emerged as an
      effective procedure to treat resistant hypertension by blocking the sympathetic
      nervous system. The medical device industry has developed various catheters in an
      effort to achieve better denervation in the absence of available testing to
      document adequate denervation. By adding a sham control group to the study
      design, researchers found that the results of the Renal Denervation in Patients
      With Uncontrolled Hypertension study (SYMPLICITY HTN-3) showed that renal
      denervation was not superior to placebo in decreasing systolic blood pressure.
      Although SYMPLICITY HTN-3 successfully addressed many issues that might have
      biased the previously published data, incomplete denervation caused by limited
      operator experience, catheter design, and the radiofrequency ablation technology
      may have accounted for the discrepancy of the results. This, along with
      differences in the study design and population, should direct future renal
      denervation studies. This article reviews the available literature and proposes
      future directions for renal denervation studies. It also provides a detailed
      comparison of the available catheters and their respective clinical data. 

PMID- 26198560
TI  - Three-Dimensional Angle Assessment and Plaque Distribution Classification in Left
      Main Disease: Impact of Geometry on Outcome.
AB  - Bifurcation geometry and plaque distribution in a diseased left main artery (LM)
      have the potential to drive operators' decisions regarding treatment strategies,
      techniques, and material selection. The three-dimensional (3D) geometry of the LM
      bifurcation typically results in specific patterns of plaque distribution. Plaque
      distribution may, in turn, significantly affect the procedural and long-term
      clinical and angiographic outcomes of LM percutaneous coronary intervention. Each
      LM bifurcation must be treated according to its unique anatomic and pathologic
      characteristics. Novel classification schemes of plaque distribution and 3D
      assessment may be valuable aids to obtaining a working picture of the bifurcation
      geometry. 

PMID- 26198559
TI  - Implementation of the 2013 American College of Cardiology/American Heart
      Association Blood Cholesterol Guideline Including Data From the Improved
      Reduction of Outcomes: Vytorin Efficacy International Trial.
AB  - Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity
      and mortality in developed countries. The management of blood cholesterol through
      use of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins)
      in at-risk patients is a pillar of medical therapy for the primary and secondary
      prevention of cardiovascular disease. The recent 2013 American College of
      Cardiology/American Heart Association guideline on managing blood cholesterol
      provides an important framework for the effective implementation of risk
      reduction strategies. The guideline identifies four cohorts of patients with
      proven benefits from statin therapy and streamlines the dosing and monitoring
      recommendations based on evidence from published, randomized controlled trials.
      Primary care physicians and cardiologists play key roles in identifying
      populations at elevated ASCVD risk. In providing a practical management overview
      of the current blood cholesterol guideline, we facilitate more informed
      discussions on treatment options between healthcare providers and their patients.

PMID- 26198561
TI  - Novel Agents for the Prevention and Management of Hyperkalemia.
AB  - Hyperkalemia is defined as serum potassium concentrations elevated above the
      upper limit of normal (> 5.0 mEq/L). It has become more common in cardiovascular
      practice due to the growing population of patients with chronic kidney disease
      and the broad application of drugs that modulate renal elimination of potassium
      by reducing production of angiotensin II (angiotensin-converting enzyme
      inhibitors, direct renin inhibitors, beta-adrenergic receptor antagonists),
      blocking angiotensin II receptors (angiotensin receptor blockers), or
      antagonizing the action of aldosterone on mineralocorticoid receptors
      (mineralocorticoid receptor antagonists). The risk of hyperkalemia is a major
      limiting factor for the use of these disease-modifying drugs in both acute and
      chronic cardiorenal syndromes. Thus, agents to control the plasma concentration
      of potassium are needed in the multidrug treatment of cardiorenal disease,
      including chronic kidney disease, heart failure, and acute kidney injury. Novel
      oral therapies in development for both acute and extended use in the management
      of hyperkalemia include patiromer sorbitex calcium and sodium zirconium
      cyclosilicate. Important biochemical differences between these compounds result
      in unique product profiles and electrolyte outcomes in patients treated for
      hyperkalemia. This review highlights the major mechanisms of hyperkalemia and key
      results from randomized trials in a range of clinical scenarios in patients with,
      and at risk for, hyperkalemia. 

PMID- 26198562
TI  - Home Telemedicine in Heart Failure: A Pilot Study of Integrated Telemonitoring
      and Virtual Provider Appointments.
AB  - Congestive heart failure is a significant cause of hospitalization,
      rehospitalization, and death. Reducing hospital readmission rates is a national
      priority. Various telemonitoring devices and programs have been developed to help
      meet this goal. The Health Connect system incorporates monitoring of physiologic
      data with regular virtual provider appointments. The Health Connect system
      integrates traditional telemedicine with virtual provider appointments. Virtual
      appointments empower patients to advocate for their own health by providing
      numerous opportunities for education and feedback. In addition to early
      identification of impending decompensation, virtual appointments allow providers
      to address noncompliance, which is a major factor driving poor outcomes. Further
      research is required to confirm the benefit of the Health Connect system. 

PMID- 26198563
TI  - Update From the California Chapter of The American College of Cardiology.

PMID- 26198564
TI  - Silk Suture Embolization for Sealing Distal Coronary Artery Perforation: Report
      of Two Cases.
AB  - Coronary artery perforation (CAP) is an infrequent yet potentially life
      threatening complication of percutaneous coronary intervention. We report, for
      the first time, two cases of successful closure of guidewire-induced distal CAP
      with silk suture embolization using a microcatheter. This technique appears to be
      safe, simple, and effective for the treatment of distal guidewire perforations,
      even in refractory cases. 

PMID- 26198565
TI  - Vortex chain formation in regions of ion concentration polarization.
AB  - The local vortical flow generated inside an ion concentration polarization (ICP)
      region is evaluated experimentally. The ICP is induced by a patterned nanoporous
      self-assembling membrane integrated inside a single microchannel. A bottom-view
      image of the depletion region near the membrane revealed a primary vortex which
      results from the electric field amplification. A unique perspective of the flow
      is obtained by imaging the microchannel from its side. This visualization shows
      for the first time the formation of a chain of three vortices all rotating in the
      same direction in the depletion region. While observation of multiple vortices
      has been previously reported, it was in reference to counter rotating vortex
      pairs and not to the same direction of rotating vortex chain formation. A
      physical model is proposed which considers a two dimensionally varying
      concentration profile in the depletion region to account for the formation of
      multiple vortices rotating in the same direction. The fast rotating primary
      vortex changes the local concentration in regions adjacent to it, as the
      advection time scale is much higher than the diffusion time scale. Near the
      membrane, it moves the low concentration electrolyte from the bottom wall upwards
      into a higher concentration region. Away from the membrane, it moves the high
      concentration electrolyte from the middle of the channel downwards into a low
      concentration region. These local changes in the wall concentration result in a
      varying slip velocity capable of inducing a secondary vortex. Similarly, this
      secondary vortex can induce a tertiary one. A numerical simulation is performed
      using the proposed varying slip velocity model which showed excellent agreement
      with the experimental observations. 

PMID- 26198566
TI  - Exendin-4 Enhances Motor Function Recovery via Promotion of Autophagy and
      Inhibition of Neuronal Apoptosis After Spinal Cord Injury in Rats.
AB  - Autophagy occurs prior to apoptosis and plays an important role in cell death
      regulation during spinal cord injury (SCI). This study aimed to determine the
      effects and potential mechanism of the glucagon-like peptide-1 (GLP-1) agonist
      extendin-4 (Ex-4) in SCI. Seventy-two male Sprague Dawley rats were randomly
      assigned to sham, SCI, 2.5 MUg Ex-4, and 10 MUg Ex-4 groups. To induce SCI, a 10
      g iron rod was dropped from a 20-mm height to the spinal cord surface. Ex-4 was
      administered via intraperitoneal injection immediately after surgery. Motor
      function evaluation with the Basso Beattie Bresnahan (BBB) locomotor rating scale
      indicated significantly increased scores (p < 0.01) in the Ex-4-treated groups,
      especially 10 MUg, which demonstrated the neuroprotective effect of Ex-4 after
      SCI. The light chain 3-II (LC3-II) and Beclin 1 protein expression determined via
      western blot and the number of autophagy-positive neurons via immunofluorescence
      double labeling were increased by Ex-4, which supports promotion of autophagy (p
      < 0.01). The caspase-3 protein level and neuronal apoptosis via transferase UTP
      nick end labeling (TUNEL)/NeuN/DAPI double labeling were significantly reduced in
      the Ex-4-treated groups, which indicates anti-apoptotic effects (p < 0.01).
      Finally, histological assessment via Nissl staining demonstrated the Ex-4 groups
      exhibited a significantly greater number of surviving neurons and less cavity (p
      < 0.01). To our knowledge, this is the first study to indicate that Ex-4
      significantly enhances motor function in rats after SCI, and these effects are
      associated with the promotion of autophagy and inhibition of apoptosis.

PMID- 26198568
TI  - Simvastatin Enhances Spatial Memory and Long-Term Potentiation in Hippocampal CA1
      via Upregulation of alpha7 Nicotinic Acetylcholine Receptor.
AB  - Simvastatin (SV) has been reported to improve cognitive deficits in Alzheimer's
      disease. Here, we show that chronic administration of SV (20 mg/kg) for 30 days
      in adult mice (SV mice) enhanced spatial cognitive performance as assessed by
      Morris water maze and Y-maze. To explore mechanisms underlying SV-enhanced
      spatial cognition, we further examined synaptic properties and long-term
      potentiation (LTP) in hippocampal CA1, hippocampal alpha7nAChR expression, and
      Akt and ERK2 phosphorylation. In comparison with controls, the SV administration
      caused increase in presynaptic glutamate release and amplitude of NMDAr-dependent
      LTP (LTP-augmentation), and decrease in threshold of NMDAr-independent LTP
      induction (LTP-facilitation). The supplement of isoprenoid farnesyl pyrophosphate
      (FPP) by applying farnesol (FOH) could abolish the spatial cognitive
      potentiation, increased glutamate release, and LTP-augmentation/facilitation in
      SV mice. Expression of alpha7nAChR, but not alpha4beta2nAChR, was increased in
      hippocampal pyramidal cells of SV mice with the reduction of transcription factor
      AP-2alpha, which were abolished by FOH. Levels of Akt and ERK2 phosphorylation in
      SV mice were elevated, which were suppressed by FOH or alpha7nAChR antagonist
      methyl-lycaconitine (MLA). In hippocampal slices obtained from SV mice, acute
      perfusion of MLA blocked the increased glutamate release, whereas FOH, PI3K
      inhibitor LY294002, or MEK inhibitor U0126 could not. In the slices of SV mice,
      the perfusion of MLA or U0126, but not FOH, abolished the LTP-augmentation and
      LTP-facilitation. By contrast, LY294002 prevented the LTP-facilitation but failed
      to affect the LTP-augmentation. The findings indicate that the administration of
      SV through reducing FPP increases alpha7nAChR expression and alpha7nAChR-related
      Akt and ERK2 phosphorylation, leading to LTP enhancement and spatial cognitive
      potentiation.

PMID- 26198570
TI  - Lithium Treatment for Post-Head Injury Volatility.

PMID- 26198567
TI  - Oxidative Stress in Neurodegenerative Diseases.
AB  - The pathophysiologies of neurodegenerative diseases, including amyotrophic
      lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD),
      are far from being fully explained. Oxidative stress (OS) has been proposed as
      one factor that plays a potential role in the pathogenesis of neurodegenerative
      disorders. Clinical and preclinical studies indicate that neurodegenerative
      diseases are characterized by higher levels of OS biomarkers and by lower levels
      of antioxidant defense biomarkers in the brain and peripheral tissues. In this
      article, we review the current knowledge regarding the involvement of OS in
      neurodegenerative diseases, based on clinical trials and animal studies. In
      addition, we analyze the effects of the drug-induced modulation of oxidative
      balance, and we explore pharmacotherapeutic strategies for OS reduction.

PMID- 26198569
TI  - Selected Micronutrients in Cognitive Decline Prevention and Therapy.
AB  - Population aging is a worldwide demographic trend. Consequently, the prevalence
      of chronic age-related conditions such as clinically diagnosed neurological
      diseases, cognitive decline, and dementia will significantly increase in the near
      future. The important role of diets and healthy lifestyle as preventative of
      neurodegenerative diseases is widely accepted nowadays, and it may provide
      preventive strategies in very early, non-symptomatic phases of dementia well,
      especially because there are still no effective treatments for it. In this
      article, we review the known effects of selected micronutrients on the aging
      brain and we propose strategies for dietary improvements.

PMID- 26198571
TI  - Prognostic Significance of Postoperative Subsyndromal Delirium.
AB  - BACKGROUND: Whether postoperative subsyndromal delirium (SSD) is a separate
      syndrome from delirium and has clinical relevance is not well understood.
      OBJECTIVES: We sought to investigate SSD in older surgical patients and to
      determine its prognostic significance. METHODS: We performed a prospective cohort
      study of patients who were 65 years or older and were scheduled for noncardiac
      surgery. Postoperative delirium was determined using the Confusion Assessment
      Method. SSD was defined as the presence of at least one of the possible 10
      symptoms of delirium, as defined by the Confusion Assessment Method, but not
      meeting the criteria for delirium. RESULTS: The number of features of SSD on the
      first postoperative day was associated with the subsequent development of
      delirium on the next day, after controlling for other risk factors. When compared
      with a patient with no SSD features, a patient with 1 SSD feature was 1.07 times
      more likely to have delirium on the next day (95% CI: 0.42-2.53), with 2 features
      was 3.32 times more likely to have it (95% CI: 1.42-7.57), and with >= 2 features
      was 8.37 times more likely to have it (95% CI: 4.98-14.53). Furthermore, there
      was a significant relationship between the number of features of SSD and
      increased length of hospital stay and worsened functional status at 1 month after
      surgery. CONCLUSIONS: SSD is prevalent in at-risk surgical patients and has
      prognostic significance. Only a single symptom of SSD was sufficient to cause a
      significant increase in hospital length of stay and further decline in functional
      status. These results suggest that monitoring for SSD is indicated in at-risk
      patients.

PMID- 26198572
TI  - The Perils of Illegitimate Online Pharmacies: Substance-Induced Panic Attacks and
      Mood Instability Associated With Selegiline and Phenylethylamine.

PMID- 26198573
TI  - A cluster randomized controlled trial on the effects and costs of advance care
      planning in elderly care: study protocol.
AB  - BACKGROUND: Currently, health care and medical decision-making at the end of life
      for older people are often insufficiently patient-centred. In this trial we study
      the effects of Advance Care Planning (ACP), a formalised process of timely
      communication about care preferences at the end of life, for frail older people.
      METHODS/DESIGN: We will conduct a cluster randomised controlled trial among older
      people residing in care homes or receiving home care in the Netherlands. The
      intervention group will receive the ACP program Respecting Choices(r) in addition
      to usual care. The control group will receive usual care only. Participants in
      both groups will fill out questionnaires at baseline and after 12 months. We
      hypothesize that ACP will lead to better patient activation in medical decision
      making and quality of life, while reducing the number of medical interventions
      and thus health care costs. Multivariate analysis will be used to compare
      differences between the intervention group and the control group at baseline and
      to compare differences in changes after 12 months following the inclusion.
      DISCUSSION: Our study can contribute to more understanding of the effects of ACP
      on patient activation and quality of life in frail older people. Further, we will
      gain insight in the costs and cost-effectiveness of ACP. This study will
      facilitate ACP policy for older people in the Netherlands. TRIAL REGISTRATION:
      Nederlands Trial Register: NTR4454.

PMID- 26198574
TI  - Regulation of microRNA during cardiomyocyte maturation in sheep.
AB  - BACKGROUND: There is a limited capacity to repair damage in the mammalian heart
      after birth, which is primarily due to the inability of cardiomyocytes to
      proliferate after birth. This is in contrast to zebrafish and salamander, in
      which cardiomyocytes retain the ability to proliferate throughout life and can
      regenerate their heart after significant damage. Recent studies in zebrafish and
      rodents implicate microRNA (miRNA) in the regulation of genes responsible for
      cardiac cell cycle progression and regeneration, in particular, miR-133a, the miR
      15 family, miR-199a and miR-590. However, the significance of these miRNA and
      miRNA in general in the regulation of cardiomyocyte proliferation in large
      mammals, including humans, where the timing of heart development relative to
      birth is very different than in rodents, is unclear. To determine the involvement
      of miRNA in the down-regulation of cardiomyocyte proliferation occurring before
      birth in large mammals, we investigated miRNA and target gene expression in sheep
      hearts before and after birth. The experimental approach included targeted
      transcriptional profiling of miRNA and target mRNA previously identified in
      rodent studies as well as genome-wide miRNA profiling using microarrays. RESULTS:
      The cardiac expression of miR-133a increased and its target gene IGF1R decreased
      with increasing age, reaching their respective maximum and minimum abundance when
      the majority of ovine cardiomyocytes were quiescent. The expression of the miR-15
      family members was variable with age, however, four of their target genes
      decreased with age. These latter profiles are inconsistent with the direct
      involvement of this family of miRNA in cardiomyocyte quiescence in late gestation
      sheep. The expression patterns of 'pro-proliferative' miR-199a and miR-590 were
      also inconsistent with their involvement in cardiomyocyte quiescence.
      Consequently, miRNA microarray analysis was undertaken, which identified six
      discrete clusters of miRNA with characteristic developmental profiles. The
      functions of predicted target genes for the miRNA in four of the six clusters
      were enriched for aspects of cell division and regulation of cell proliferation
      suggesting a potential role of these miRNA in regulating cardiomyocyte
      proliferation. CONCLUSION: The results of this study show that the expression of
      miR-133a and one of its target genes is consistent with it being involved in the
      suppression of cardiomyocyte proliferation, which occurs across the last third of
      gestation in sheep. The expression patterns of the miR-15 family, miR-199a and
      miR-590 were inconsistent with direct involvement in the regulation cardiomyocyte
      proliferation in sheep, despite studies in rodents demonstrating that their
      manipulation can influence the degree of cardiomyocyte proliferation. miRNA
      microarray analysis suggests a coordinated and potentially more complex role of
      multiple miRNA in the regulation of cardiomyocyte quiescence and highlights
      significant differences between species that may reflect their substantial
      differences in the timing of this developmental process.

PMID- 26198575
TI  - Effect of alcohol on diethylnitrosamine-induced hepatic toxicity: Critical role
      of ROS, lipid accumulation, and mitochondrial dysfunction.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the
      seventh in women worldwide. Chronic heavy alcohol consumption is a major risk
      factor for the development of HCC. However, the mechanism underlying the direct
      association between alcohol consumption and HCC is far from completely
      understood. In the present study, we investigated the effect of chronic
      consumption of alcohol on diethylnitrosamine (DEN)-induced cytotoxicity, which
      was essential for the malignant transformation. We showed that alcohol deceased
      survival of mice treated by DEN and promoted DEN-induced toxicity and hepatic
      injury. In addition, alcohol promoted DEN-induced increase of proinflammatory
      factors, collagen content and fibrosis-related genes, including collagen1, 3 and
      4, TMIP1, TIMP2 and TGFbeta1, and compensatory proliferation. Alcohol may
      increase alcohol dehydrogenase (ADH) and cytochrome P4502E1 (CYP2E1) expression,
      enhanced reactive oxygen species (ROS) generation, and resulted in a vicious
      circle between ROS generation, lipid accumulation, and mitochondrial dysfunction,
      aggravating liver injury and toxicity in DEN-treated mice. These results
      demonstrated that the combination of alcohol and carcinogens could aggravate
      carcinogen-induced cytotoxicity in the early phase of rumourigenesis through ADH
      and CYP2E1-generated ROS and the resultant cytotoxic process. The present study
      provided direct experimental evidence for alcohol-promoted toxicity and hepatic
      injury in carcinogen (DEN)-treated mice. 

PMID- 26198577
TI  - A primer on on-demand polymerase chain reaction technology.
AB  - Efforts to reduce health care-associated infections (HAIs) have grown in both
      scale and sophistication over the past few decades; however, the increasing
      threat of antimicrobial resistance and the impact of new legislation regarding
      HAIs on health care economics make the fight against them all the more urgent. On
      demand polymerase chain reaction (PCR) technology has proven to be a highly
      effective weapon in this fight, offering the ability to accurately and
      efficiently identify disease-causing pathogens such that targeted and directed
      therapy can be initiated at the point of care. As a result, on-demand PCR
      technology has far-reaching influences on HAI rates, health care outcomes,
      hospital length of stay, isolation days, patient satisfaction, antibiotic
      stewardship, and health care economics. The basics of on-demand PCR technology
      and its potential to impact health care have not been widely incorporated into
      health care education and enrichment programs for many of those involved in
      infection control and prevention, however. This article serves as a primer on on
      demand PCR technology and its ramifications. 

PMID- 26198576
TI  - Histomorphological comparison of rat placentas by different timing of
      chlorpromazine-administration.
AB  - The effects of chlorpromazine-treatment timing on the development of the placenta
      in pregnant rats were examined. Chlorpromazine was administered intraperitoneally
      at 100mg/kg on gestation day (GD) 11 (GD11-treated group), GD 13 (GD13-treated
      group) or GD 15 (GD15-treated group) into pregnant rats. All treated dams
      exhibited decreased body weight, prone position, hypothermia, loss or decrease of
      locomotor activity, etc. The fetal mortality rates were increased up to 42.9% in
      the GD11- and GD13-treated groups and up to 16.7% in the GD15-treated group. The
      embryo/fetal weight was on a declining trend from GD 16 onward, and the
      intrauterine growth retardation (IUGR) rates on GD 21 were increased in all
      treated groups. The placental weight showed a declining trend from GD 15 onward
      in all treated groups. Histopathologically, apoptosis was detected 1 or 2 days
      after treatment, and led to hypoplasia in the labyrinth zone and metrial gland,
      and cystic degeneration in the basal zone on GD 21 in all treated groups. There
      was no difference in the histopathological lesions on GD 21 among the treated
      groups. Thus, it is considered that chlorpromazine-induced placental toxicity is
      characterized in that there is no obvious specific sensitive period from GD 11 to
      GD 15. Chlorpromazine induced a non-specific transient development retardation of
      the placenta by apoptosis independently of the cell proliferation period in each
      part/zone. 

PMID- 26198578
TI  - Pallidal deep brain stimulation in Huntington's disease.

PMID- 26198579
TI  - Primary hyperparathyroidism in a patient with primary aldosteronism.
AB  - BACKGROUND: Primary hyperparathyroidism is one of the most common causes of
      hypercalcemia. Inherited forms of primary hyperparathyroidism like Multiple
      Endocrine Neoplasia Type 1, Multiple Endocrine Neoplasia Type 2a,
      Hyperparathyroidism-Jaw Tumor Syndrome or isolated familial tumors are not common
      for our population. RESULTS: We present a case of primary hyperparathyroidism in
      a 38-year-old Turkish man with hyperaldosteronism (Conn's syndrome). CONCLUSION:
      Genetic studies could not reveal any mutation. We could not identify any inherit
      form of the diseases. We wanted the first-line relatives examination of the
      suspected gene mutation, but they refused.

PMID- 26198580
TI  - Brevirhabdus pacifica gen. nov., sp. nov., isolated from deep-sea sediment in a
      hydrothermal vent field.
AB  - A Gram-stain-negative, motile, aerobic bacterial strain, designated 22DY15T, was
      isolated from a deep-sea sediment sample collected from a hydrothermal vent field
      located in the East Pacific Rise. The isolate was a short rod with a single
      flagellum and was positive for catalase and oxidase activities. Q-10 was the
      predominant respiratory quinone. The major polar lipids consisted of
      phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine,
      phosphoglycolipid, one aminolipid and three unidentified phospholipids. The
      principal fatty acid (>70 %) was C18 : 1omega7c. The genomic DNA G+C content was
      64.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that
      strain 22DY15T represents a distinct lineage within the family Rhodobacteraceae.
      The closest relatives were species of the genera Aliiroseovarius (93.3-96.0 % 16S
      rRNA gene sequence similarity), Sulfitobacter (94.0-96.0 %) and Loktanella (92.0
      95.9 %). Differential phenotypic properties, together with phylogenetic and
      genetic distinctiveness, revealed that strain 22DY15T could be differentiated
      from its most closely related genera. Therefore, it is proposed that strain
      22DY15T represents a novel species in a new genus of the family Rhodobacteraceae,
      for which the name Brevirhabdus pacifica gen. nov., sp. nov. is proposed. The
      type strain of the type species is 22DY15T ( = JCM 19489T = DSM 27767T = CGMCC
      1.12416T = MCCC 1K00276T).

PMID- 26198581
TI  - Symptom profile and short term outcome of catatonia: an exploratory clinical
      study.
AB  - BACKGROUND: Catatonia is a potentially life-threatening but treatable
      neuropsychiatric condition. Although considered more common in low income
      countries, data is particularly sparse in these settings. In this study we
      explore the symptomatology, treatment, and short-term outcome of catatonia in
      Ethiopia, a low income country. METHODS: The study was a prospective evaluation
      of patients admitted with a DSM-IV diagnosis of catatonia. Diagnosis of Catatonia
      and its severity were further assessed with the Bush-Francis Catatonia Rating
      Scale (BFCRS). RESULTS: Twenty participants, 5 male and 15 female, were included
      in the study: 15 patients (75 %) had underlying mood disorders, 4 patients (20 %)
      had schizophrenia and 1 patient (5 %) had general medical condition. The most
      common catatonic symptoms, occurring in over two-thirds of participants, were
      mutism, negativism, staring and immobility (stupor). Eighteen (90 %) of the
      twenty patients were on multiple medications. Antipsychotics were the most
      commonly prescribed medications. ECT was required in seven patients (35.0 %).
      Dehydration, requiring IV rehydration, and infections were the most important
      complications ascribed to the catatonia. These occurred in seven patients (25 %).
      Almost all patients (n = 19/20) were discharged with significant improvement.
      CONCLUSION: This study supports the growing consensus that catatonia is most
      often associated with mood disorders. Overall prognosis appears very good
      although the occurrence of life-threatening complications underlines the serious
      nature of catatonia. This has implication for "task-shifted" service scale up
      plans, which aim to improve treatment coverage by training non-specialist health
      workers to provide mental health care in low income countries. Further larger
      scale studies are required to clarify the nature and management, as well as,
      service requirements for catatonia.

PMID- 26198582
TI  - The Relationship between Number of Fruits, Vegetables, and Noncore Foods Tried at
      Age 14 Months and Food Preferences, Dietary Intake Patterns, Fussy Eating
      Behavior, and Weight Status at Age 3.7 Years.
AB  - OBJECTIVE: We examined whether exposure to a greater number of fruits,
      vegetables, and noncore foods (ie, nutrient poor and high in saturated fats,
      added sugars, or added salt) at age 14 months was related to children's
      preference for and intake of these foods as well as maternal-reported food
      fussiness and measured child weight status at age 3.7 years. METHODS: This study
      reports secondary analyses of longitudinal data from mothers and children (n=340)
      participating in the NOURISH randomized controlled trial. Exposure was quantified
      as the number of food items (n=55) tried by a child from specified lists at age
      14 months. At age 3.7 years, food preferences, intake patterns, and fussiness
      (also at age 14 months) were assessed using maternal-completed, established
      questionnaires. Child weight and length/height were measured by study staff at
      both age points. Multivariable linear regression models were tested to predict
      food preferences, intake patterns, fussy eating, and body mass index z score at
      age 3.7 years adjusting for a range of maternal and child covariates. RESULTS:
      Having tried a greater number of vegetables, fruits, and noncore foods at age 14
      months predicted corresponding preferences and higher intakes at age 3.7 years
      but did not predict child body mass index z score. Adjusting for fussiness at age
      14 months, having tried more vegetables at age 14 months was associated with
      lower fussiness at age 3.7 years. CONCLUSIONS: These prospective analyses support
      the hypothesis that early taste and texture experiences influence subsequent food
      preferences and acceptance. These findings indicate introduction to a variety of
      fruits and vegetables and limited noncore food exposure from an early age are
      important strategies to improve later diet quality.

PMID- 26198583
TI  - Deriving nutrition information using mathematical estimation: the example of
      phenylalanine in sweets with gelatin.

PMID- 26198584
TI  - Trends in Warfarin Monitoring Practices Among New York Medicare Beneficiaries,
      2006-2011.
AB  - Anticoagulation with warfarin requires frequent evaluation of the international
      normalized ratio (INR), and less invasive testing devices are available for use
      by clinicians at the point-of-care (POC) and by patients who self-test (PST).
      Despite commercial availability and positive results of published studies,
      evidence suggests that adoption of less invasive (POC/PST) testing in the United
      States is slow. Considering the equivalence of results and logistical advantages
      of POC/PST testing, slow uptake may indicate a gap in quality of care warranting
      evaluation and possibly intervention. This study used Medicare fee for service
      claims data to explore the uptake of POC/PST INR monitoring across New York State
      over a 6 year time frame (2006-11), with additional analyses based on beneficiary
      age, sex, race and ethnicity and income by county. In 2006, only 28.3% of 103,410
      analyzable beneficiaries presumed to be chronic warfarin users based on INR
      testing patterns were monitored by POC/PST, and increased to only 37.6% by 2011.
      Utilization of POC/PST testing varied widely by county (baseline range 1.2
      89.4%), and uptake of these testing modalities in New York State was
      significantly lower among the very elderly, women, and ethnic minorities. We
      hypothesize that poor penetration of these less invasive INR testing modalities
      into highly populated New York City and barriers to POC utilization in long term
      care facilities may account for a portion of the variability in INR testing
      patterns observed in this study. However, additional research is needed to
      further explore whether disparities in warfarin monitoring practices exist.

PMID- 26198585
TI  - Detection of mutually exclusive mosaicism in a girl with genotype-phenotype
      discrepancies.
AB  - Discordance between clinical phenotype and genotype has multiple causes,
      including mosaicism. Phenotypes can be modified due to tissue distribution, or
      the presence of multiple abnormal cell lines with different genomic
      contributions. We have studied a 20-month-old female whose main phenotypes were
      failure to thrive, developmental delay, and patchy skin pigmentation. Initial
      chromosome and SNP microarray analysis of her blood revealed a non-mosaic ~24 Mb
      duplication of 15q25.1q26.3 resulting from the unbalanced translocation of
      terminal 15q to the short arm of chromosome 15. The most common feature
      associated with distal trisomy 15q is prenatal and postnatal overgrowth, which
      was not consistent with this patient's phenotype. The phenotypic discordance, in
      combination with the patchy skin pigmentation, suggested the presence of
      mosaicism. Further analysis of skin biopsies from both hyper- and hypopigmented
      regions confirmed the presence of an additional cell line with the short arm of
      chromosome X deleted and replaced by the entire long arm of chromosome 15. The Xp
      deletion, consistent with a variant Turner Syndrome diagnosis, better explained
      the patient's phenotype. Parental studies revealed that the alterations in both
      cell lines were de novo and the duplicated distal 15q and the deleted Xp were
      from different parental origins, suggesting a mitotic event. The possible
      mechanism for the occurrence of two mutually exclusive structural rearrangements
      with both involving the long arm of chromosome 15 is discussed.

PMID- 26198586
TI  - Is entheses ultrasound reliable? A reading Latin American exercise.
AB  - The objective of this study is to evaluate inter-reader entheses ultrasound (US)
      reliability and the influence of the type of image or degree of sonographer
      experience on US reliability in patients with spondyloarthritis (SpA). Eighteen
      Latin American ultrasonographers with different experience took part in an US
      reading exercise evaluating 60 entheseal images (50 % static images and 50 %
      videos) from healthy controls and SpA patients. The following sonographic lesions
      were assessed: structure, thickness, bone proliferation/tendon calcification,
      erosions, bursitis, and Doppler signal. Another group of three experts with
      significant experience in entheses US read all images too. Inter-reader
      reliability among participants and experts was calculated by the Cohen's kappa
      coefficient. Thresholds for kappa values were <0.2 poor, 0.21-0.4 fair, 0.41-0.6
      moderate, 0.61-0.8 good, and 0.81-1 excellent. Furthermore, the results for the
      expert group were stratified based on the type of image. Kappa correlation
      coefficients among participants, showed variability depending on the type of
      lesion, being fair for structure and thickness, moderate for calcifications,
      erosions, and bursitis, and excellent for Doppler signal. Inter-reader
      reliability among experts was higher, being moderate for structure and thickness,
      good for calcifications and bursitis, and excellent for erosions and Doppler.
      Inter-reader reliability for assessing calcification and structure using static
      images was significantly higher than for videos. Overall inter-reader reliability
      for assessing entheses by US in SpA is moderate to excellent for most of the
      lesions. However, special training seems fundamental to achieve better inter
      reader reliability. Moreover, the type of image influenced these results, where
      evaluation of entheses by videos was more difficult than by static images. 

PMID- 26198587
TI  - Help-seeking trajectory in patients with rheumatoid arthritis.
AB  - Early diagnosis and treatment of rheumatoid arthritis (RA) depends on the degree
      of fit between the characteristics of the patients and those of the health
      services. Ensuring timely assessment and treatment is the ideal medical care of
      RA. The reasons that underlay delays and the help-seeking trajectories are
      contextually determined. This study aims to identify the empirical evidence
      related to the help-seeking process and delay in RA in Latin America and to
      create a comprehensive model integrating the RA medical care processes of help
      seeking and delay in a mixed health care system with variable accessibility. Non
      systematic literature review of studies with both quantitative and qualitative
      methodology was conducted. Most of the research about delay and its associated
      variables have been undertaken in European countries and with White population
      and cannot be translated to the Latin America context where this research is
      almost inexistent. These countries have a completely different social context,
      and for most of the population, the health services are insufficient,
      inaccessible, fragmented, limited, and inequitable. Our results also show that in
      RA medical care utilization research, the theories and measurements of the
      constructs of illness trajectories, help-seeking, and accessibility are not
      integrated. We offer a conceptual framework that integrates help-seeking
      trajectories, delay, and accessibility of RA medical health services. If research
      on RA service utilization is to be undertaken in these countries, there is a need
      for a comprehensive framework than can enable researchers to integrate and
      contextualize the study of the problems within broad theoretical and
      methodological perspectives.

PMID- 26198589
TI  - Chronic osteomyelitis as a risk factor for development of rheumatoid arthritis: a
      nationwide, population-based, cohort study.
AB  - An association between occult infection and the development of rheumatoid
      arthritis (RA) has been suggested. This study aimed to determine if patients with
      chronic osteomyelitis (COM) are at increased risk of developing RA. A national
      insurance claim dataset of 22 million enrollees in Taiwan was used to identify
      21,105 hospital inpatients with COM and 84,420 reference subjects matched by sex,
      age, and index date of diagnosis with a mean of 5.12 years of follow-up from 2000
      to 2011. The risk of RA development was analyzed using Cox proportional hazards
      modeling. The mean age of hospital inpatients with COM was 55.8 +/- 19.4 years.
      The incidence of RA was 5.43 per 10(4) person-years in the case cohort, which was
      more than twofold higher than that of 2.20 per 10(4) person-years in the
      reference cohort. After adjustment, the hazard ratio (HR) was 2.21 (95 %
      confidence interval, 1.51-3.24). The HR was greatest in the youngest age group
      (<45 years, HR [95 % confidence interval] = 9.08 [3.22-25.6]; 45-64 years, 1.76
      [1.01-3.06]; >=65 years, 1.68 [0.88-3.24]). In addition, HR was greatest in
      inpatients with more severe COM (HR [95 % confidence interval] = 0.72 [0.40-1.30]
      and 11.2 [6.63-18.9] for patients with <=1 or >2 hospitalization due to recurrent
      osteomyelitis every two follow-up years, respectively). This is the first report
      linking COM to risk of incident RA. Patients of a younger age and with frequently
      recurrent COM had a greater increase in RA risk.

PMID- 26198588
TI  - Proper management of rheumatoid arthritis in Latin America. What the guidelines
      say?
AB  - To analyze characteristics of clinical practice guidelines (CPGs) for the
      management of rheumatoid arthritis (RA) developed in Latin American (LA)
      countries and to describe the knowledge, use, and barriers for their
      implementation perceived among LA rheumatologists, a comprehensive literature
      search including Medline, PubMed, Cochrane Library, LILACS and Scielo was
      performed. The Appraisal of Guidelines for Research and Evaluation (AGREE)
      instrument was applied for evaluation. A survey was sent to PANLAR members
      containing questions related to knowledge about guidelines, application of the
      recommendations, and difficulties in implementing CPGs. Eight guidelines were
      identified. Most guidelines were evidence based (62 %), but in only 37 % a
      systematic literature search was done. None of the guidelines included patients'
      views and preferences, and only few of them stated an updating procedure. Funding
      body independence and disclosure of conflicts of interest were rarely reported.
      The survey was answered by 214 rheumatologists from all Latin American countries.
      Most rheumatologist reported knowledge and use of clinical guidelines, mainly
      international ones. In general, rheumatologist felt that guidelines apply to only
      a minority of patients seen in daily clinical practice. Limited access expensive
      drugs, suggested by the guidelines, was the most frequent barrier to guidelines
      implementation that was reported. A good number of guidelines on the treatment of
      rheumatoid arthritis have been developed in Latin America. Most of them are
      lacking some of the components recognized for high-quality clinical guidelines
      development. In spite that most rheumatologist know and apply guidelines, access
      to drugs is still a very important barrier to their implementation in Latin
      America.

PMID- 26198590
TI  - Predicting the Agitation-Induced Aggregation of Monoclonal Antibodies Using
      Surface Tensiometry.
AB  - Adsorption of antibody therapeutics to air-liquid interfaces can enhance
      aggregation, particularly when the solution does not contain protective
      surfactant or when the surfactant is diluted as occurs during preparation of
      intravenous infusion bags. The ability to predict an antibody's propensity for
      interfacially mediated aggregation is particularly useful during product
      development to ensure the quality, potency, and safety of the therapeutic. To
      develop a predictive tool, we investigated the surface pressure and surface
      excess of a panel of 16 antibodies as well as determined their aggregation
      propensity at the air-liquid interface in an agitation stress model. Our data
      demonstrated that the initial rate of surface pressure increase upon antibody
      adsorption to the air-liquid interface strongly predicted the extent of agitation
      induced aggregation. Other factors, including the hydrophobicity, equilibrium
      surface pressure, and interfacial concentration of an antibody, were not adequate
      predictors of its susceptibility to aggregation. In addition to developing a
      predictive tool, we extended the interfacial characterization to better
      understand the mechanisms of antibody aggregation at an air-liquid interface
      during agitation stress. We believe that the kinetics of antibody rearrangement
      and conformational change after adsorbing to the interface, leading to the
      development of attractive antibody-antibody interactions, dictated the extent of
      aggregation. Overall, our results demonstrate how surface pressure measurements
      can be implemented as a rapid screening tool for the identification of antibodies
      with a high propensity to aggregate upon adsorption to an air-liquid interface
      while also furthering our understanding of interfacially mediated protein
      aggregation. 

PMID- 26198591
TI  - Altered PDE10A expression detectable early before symptomatic onset in
      Huntington's disease.
AB  - There is an urgent need for early biomarkers and novel disease-modifying
      therapies in Huntington's disease. Huntington's disease pathology involves the
      toxic effect of mutant huntingtin primarily in striatal medium spiny neurons,
      which highly express phosphodiesterase 10A (PDE10A). PDE10A hydrolyses cAMP/cGMP
      signalling cascades, thus having a key role in the regulation of striatal output,
      and in promoting neuronal survival. PDE10A could be a key therapeutic target in
      Huntington's disease. Here, we used combined positron emission tomography (PET)
      and multimodal magnetic resonance imaging to assess PDE10A expression in vivo in
      a unique cohort of 12 early premanifest Huntington's disease gene carriers with a
      mean estimated 90% probability of 25 years before the predicted onset of clinical
      symptoms. We show bidirectional changes in PDE10A expression in premanifest
      Huntington's disease gene carriers, which are associated with the probability of
      symptomatic onset. PDE10A expression in early premanifest Huntington's disease
      was decreased in striatum and pallidum and increased in motor thalamic nuclei,
      compared to a group of matched healthy controls. Connectivity-based analysis
      revealed prominent PDE10A decreases confined in the sensorimotor-striatum and in
      striatonigral and striatopallidal projecting segments. The ratio between higher
      PDE10A expression in motor thalamic nuclei and lower PDE10A expression in
      striatopallidal projecting striatum was the strongest correlate with higher
      probability of symptomatic conversion in early premanifest Huntington's disease
      gene carriers. Our findings demonstrate in vivo, a novel and earliest
      pathophysiological mechanism underlying Huntington's disease with direct
      implications for the development of new pharmacological treatments, which can
      promote neuronal survival and improve outcome in Huntington's disease gene
      carriers. 

PMID- 26198592
TI  - Anti-Jo-1 antibody-positive patients show a characteristic necrotizing
      perifascicular myositis.
AB  - Idiopathic inflammatory myopathies can be classified as polymyositis,
      dermatomyositis, immune-mediated necrotizing myopathy, sporadic inclusion body
      myositis or non-specific myositis. Anti-Jo-1 antibody-positive patients are
      assigned to either polymyositis or dermatomyositis suggesting overlapping
      pathological features. We aimed to determine if anti-Jo-1 antibody-positive
      myopathy has a specific morphological phenotype. In a series of 53 muscle
      biopsies of anti-Jo-1 antibody-positive patients, relevant descriptive criteria
      defining a characteristic morphological pattern were identified. They were tested
      in a second series of anti-Jo-1 antibody-positive patients and compared to 63
      biopsies from patients suffering from other idiopathic inflammatory myopathies.
      In anti-Jo-1 antibody-positive patients, necrotic fibres, which strongly
      clustered in perifascicular regions, were frequently observed. Sarcolemmal
      complement deposition was detected specifically in perifascicular areas.
      Inflammation was mainly located in the perimysium and around vessels in 90.6%.
      Perimysial fragmentation was observed in 90% of cases. Major histocompatibility
      complex class I staining was diffusely positive, with a perifascicular
      reinforcement. Multivariate analysis showed that criteria defining perifascicular
      pathology: perifascicular necrosis, atrophy, and perimysial fragmentation allow
      the distinction of anti-Jo-1 antibody-positive patients, among patients suffering
      from other idiopathic inflammatory myopathies. Anti-Jo-1 antibody-positive
      patients displayed perifascicular necrosis, whereas dermatomyositis patients
      exhibited perifascicular atrophy. 

PMID- 26198593
TI  - Neuropsychological and psychological interventions for people with newly
      diagnosed epilepsy.
AB  - BACKGROUND: Many people with epilepsy report experiencing psychological
      difficulties such as anxiety, depression and neuropsychological deficits
      including memory problems. Research has shown that these difficulties are often
      present not only for people with chronic epilepsy but also for people with newly
      diagnosed epilepsy. Despite this, there are very few published interventions that
      detail means to help people with newly diagnosed epilepsy manage these problems.
      OBJECTIVES: To identify and assess possible psychological and neuropsychological
      interventions for adults with newly diagnosed epilepsy. SEARCH METHODS: We
      searched the following databases on 30 June 2015: the Cochrane Epilepsy Group
      Specialized Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE (Ovid), SCOPUS, PsycINFO, CINAHL, ClinicalTrials.gov and the
      World Health Organization (WHO) International Clinical Trials Registry Platform
      (ICTRP). SELECTION CRITERIA: This review includes all randomised controlled
      trials, quasi-randomised controlled trials, prospective cohort controlled
      studies, and prospective before and after studies which include psychological or
      neuropsychological interventions for people with newly diagnosed epilepsy. We
      excluded studies that included people with epilepsy and any other psychological
      disorder or neurological condition. We excluded studies carried out which
      recruited only children. DATA COLLECTION AND ANALYSIS: We used the standard
      methodological procedure expected by The Cochrane Collaboration. Two authors
      independently completed data extraction and risk of bias analysis. The results of
      this were cross-checked and third author resolved any discrepancies. In the event
      of missing data, we contacted the study authors. Meta-analysis was not completed
      due to differences in the intervention and outcomes reported in the two studies.
      MAIN RESULTS: We included two randomised controlled trials assessing
      psychological interventions for people with newly diagnosed epilepsy. One study
      assessed a cognitive behavioural intervention (CBI) in an adolescent population.
      This study was rated as low quality. One study assessed a specialist nurse
      intervention in an adult population. This study was rating as very low quality.We
      rated one study as having unclear risk of bias and one study as having high risk
      of bias.The CBI study indicated that this intervention could significantly reduce
      depressive symptoms in people with subthreshold depressive disorder. However, the
      study assessing the effectiveness of a nurse intervention found no significant
      benefit for depressive symptoms,but did find that in individuals with the least
      knowledge of epilepsy, a nurse intervention could increase their knowledge of
      epilepsy scores. AUTHORS' CONCLUSIONS: Meta-analysis was not possible as we
      identified only two studies and they utilised different interventions and outcome
      measures.Previous research has highlighted the impact of psychological and
      neuropsychological difficulties experienced by people with epilepsy and the
      negative effect this has on their quality of life. The main finding of this
      review is that there is a paucity of research assessing possible
      neuropsychological and psychological interventions for adults with newly
      diagnosed epilepsy.

PMID- 26198594
TI  - Quantitative ultrasound measurements of bone quality in female adolescents with
      idiopathic scoliosis compared to normal controls.
AB  - OBJECTIVE: The aims of this study were to compare the speed-of-sound (SOS)
      between adolescent idiopathic scoliosis (AIS) patients and controls using
      quantitative ultrasound examination and to further analyze the relationship
      between the SOS and curve type, curve magnitude, maturation status and Risser's
      sign in AIS patients compared to controls. METHODS: Seventy-eight female AIS
      patients and 58 healthy female controls 10 to 16 years of age were recruited to
      participate. Quantitative ultrasound measurements were performed at the non
      dominant distal end of the radius. The standard method for estimating the SOS and
      z-score was used. Comparisons were made between the SOS values and z-score in AIS
      patients and age-matched Asian adolescents. RESULTS: The SOS values of the
      patients were significantly lower than the controls (P < .01). The percentage of
      cases with low bone quality was 25% in the entire AIS sample. The prevalence of
      low bone quality in AIS patients was 20.5%. However, there were no correlations
      between the SOS and types of scoliosis (P > .05). The SOS values among different
      severity groups were significant, particularly between the 10 degrees  to 19
      degrees  and 20 degrees  to 39 degrees  groups as well as between 10 degrees  to
      19 degrees  and >=40 degrees  groups. However, there was no significant
      correlation between the SOS and Cobb angles. Significant correlations were also
      found between the pre- and post-menarchy status in patients. There was a
      significant difference in the SOS values for different Rissers' signs (P < .05).
      CONCLUSIONS: Compared to nonscoliotic controls, subjects with AIS had a generally
      lower SOS, indicating lower bone quality. The age, Risser's sign, or maturation
      status, may have an effect on the bone quality; however, the curve type and
      magnitude do not affect the bone quality. The results of this study indicate that
      slower bone maturation may affect the bone quality in adolescents with AIS.

PMID- 26198595
TI  - Consistency and malleability of manipulation performance in experienced
      clinicians: a pre-post experimental design.
AB  - OBJECTIVE: The purpose of this study was to sample the stability of spinal
      manipulation performance in peak impulse force development over time and the
      ability of clinicians to adapt to arbitrary target levels with short-duration
      training. METHODS: A pre-post experimental design was used. Human analog
      mannequins provided standardized simulation for performance measures. A
      convenience sample was recruited consisting of 41 local doctors of chiropractic
      with 5 years of active clinical practice experience. Thoracic impulse force was
      measured among clinicians at baseline, after 4 months at pretraining, and again
      posttraining. Intraclass correlation coefficient values and within-subject
      variability defined consistency. Malleability was measured by reduction of error
      (paired t tests) in achieving arbitrary targeted levels of force development
      normalized to the individual's typical performance. RESULTS: No difference was
      observed in subgroup vs baseline group characteristics. Good consistency was
      observed in force-time profiles (0.55 <= intraclass correlation coefficient <=
      0.75) for force parameters over the 4-month interval. With short intervals of
      focused training, error rates in force delivery were reduced by 23% to 45%,
      depending on target. Within-subject variability was 1/3 to 1/2 that of between
      subject variability. Load increases were directly related to rate of loading.
      CONCLUSION: The findings of this study show that recalibration of spinal
      manipulation performance of experienced clinicians toward arbitrary target values
      in the thoracic spine is feasible. This study found that experienced clinicians
      are internally consistent in performance of procedures under standardized
      conditions and that focused training may help clinicians learn to modulate
      procedure characteristics.

PMID- 26198596
TI  - Liquid extraction surface analysis field asymmetric waveform ion mobility
      spectrometry mass spectrometry for the analysis of dried blood spots.
AB  - Liquid extraction surface analysis (LESA) is a surface sampling technique that
      allows electrospray mass spectrometry analysis of a wide range of analytes
      directly from biological substrates. Here, we present LESA mass spectrometry
      coupled with high field asymmetric waveform ion mobility spectrometry (FAIMS) for
      the analysis of dried blood spots on filter paper. Incorporation of FAIMS in the
      workflow enables gas-phase separation of lipid and protein molecular classes,
      enabling analysis of both haemoglobin and a range of lipids (phosphatidylcholine
      or phosphatidylethanolamine, and sphingomyelin species) from a single extraction
      sample. The work has implications for multiplexed clinical assays of multiple
      analytes. 

PMID- 26198597
TI  - Exaggerated IDO1 expression and activity in Langerhans cells from patients with
      atopic dermatitis upon viral stimulation: a potential predictive biomarker for
      high risk of Eczema herpeticum.
AB  - BACKGROUND: Atopic dermatitis (AD) is a heterogenous and highly complex disease
      characterized by an increased microbial colonization. For unknown reasons, a
      subgroup of patients with AD develops Eczema herpeticum (EH), a severe viral
      complication due to spreading of herpes simplex virus (HSV). Indoleamine 2,3
      dioxygenase (IDO1) is a tryptophan (Trp)-catabolizing enzyme which is assumed to
      be instrumental in the antibacterial and antiviral defence mechanisms. METHODS:
      Comparative investigation of the IDO1 expression and activity in freshly isolated
      monocytes, plasmacytoid DC (pDC) and in vitro-generated Langerhans cells (LC)
      obtained from AD patients with HSV infections and EH and nonatopic controls.
      RESULTS: We demonstrate an increase in Trp degradation in the serum of patients
      during acute EH episodes. Circulating pDC from patients with history of EH
      display an increased IDO1 expression. An increased Trp degradation is detected in
      the supernatants of circulating monocytes from AD patients with acute EH. Mature
      LC from AD patients with history of EH and with acute EH display an increased
      IDO1 expression and activity, respectively. In LC from patients with history of
      EH, viral signals induce an exaggerated IDO1 expression and activity. CONCLUSION:
      IDO1 expression and activity in LC seem to be involved in the pathophysiology of
      EH in AD and could represent a predictive biomarker for patients with risk to
      develop EH and other viral complications.

PMID- 26198598
TI  - An improved model of predicting hepatocarcinogenic potential in rats by using
      gene expression data.
AB  - Carcinogenicity studies using animals are expensive and time consuming.
      Therefore, the development of a highly accurate carcinogenicity prediction system
      to interpret short-term test results would be beneficial. The Ames test is
      popular for mutagens; however, it cannot detect non-genotoxic carcinogens.
      Previously, we reported a prediction system using gene expression data obtained
      from a short-term (28-day) study that screened candidate compounds for testing in
      long-term carcinogenicity studies. In this study, our system was improved by
      adding more gene expression data. To establish our new system, we used the data
      of 93 test compounds (41 hepatocarcinogens and 52 non-hepatocarcinogens).
      Analysis of liver gene expression data by dividing compounds into 'for training'
      and 'for test' categories (20 cases assigned randomly) using Support Vector
      Machine (SVM) identified a set of marker probe sets that could be used to predict
      hepatocarcinogenicity. The assigned 42 probe sets have included the cancer- or c
      Myc-related genes such as Hsp90, Pink1, Hspc111, Fbx29, Hepsin, Syndecan2 and
      Synbindin. Compared with the older version, the improved system had a higher
      concordance rate with the training data and a good performance with the external
      test data.

PMID- 26198599
TI  - Contemporary Considerations for Constructing a Genetic Risk Score: An Empirical
      Approach.
AB  - Genetic risk scores are an increasingly popular tool for summarizing the
      cumulative risk of a set of Single Nucleotide Polymorphisms (SNPs) with disease.
      Typically only the set of the SNPs that have reached genome-wide significance
      compose these scores. However recent work suggests that including additional SNPs
      may aid risk assessment. In this paper, we used the Atherosclerosis Risk in
      Communities (ARIC) Study cohort to illustrate how one can choose the optimal set
      of SNPs for a genetic risk score (GRS). In addition to P-value threshold, we also
      examined linkage disequilibrium, imputation quality, and imputation type. We
      provide a variety of evaluation metrics. Results suggest that P-value threshold
      had the greatest impact on GRS quality for the outcome of coronary heart disease,
      with an optimal threshold around 0.001. However, GRSs are relatively robust to
      both linkage disequilibrium and imputation quality. We also show that the optimal
      GRS partially depends on the evaluation metric and consequently the way one
      intends to use the GRS. Overall the implications highlight both the robustness of
      GRS and a means to empirically choose the best set of GRSs. 

PMID- 26198601
TI  - OEDIPUS REX: WHERE ARE WE GOING, ESPECIALLY WITH FEMALES?
AB  - The Oedipus myth usefully informs triangulated object relations, though males,
      females, and "humankind" can become overly interchangeable. Freud's intentions to
      enlighten sexed gender are nowadays obscured. In 1931, he rejected Oedipus for
      females. Counterreactive gender blindness forecloses exploration about female
      development. Loewald's (1979) view of Oedipus Rex emancipates male heterosexuals
      from a recurring (universal), regressive pull back to mother. Ogden (1987) offers
      further insights into earliest female development. The author suggests a
      lifelong, progressive trajectory of mother/daughter closeness, in synch with a
      girl's shared slow body development into maturity and childbearing. Freeing the
      female dyad from obligatory pathological interpretation may inspire fresh sex and
      gender clinical theory.

PMID- 26198602
TI  - PARRHESIA, PHAEDRA, AND THE POLIS: ANTICIPATING PSYCHOANALYTIC FREE ASSOCIATION
      AS DEMOCRATIC PRACTICE.
AB  - This essay explores the mostly unexamined analogy of psychoanalytic free
      association to democratic free speech. The author turns back to a time when free
      speech was a matter of considerable discussion: the classical period of the
      Athenian constitution and its experiment with parrhesia. Ordinarily translated
      into English as "free speech," parrhesia is startlingly relevant to
      psychoanalysis. The Athenian stage-in particular, Hippolytus (Euripides, 5th
      century BCE)-illustrates this point. Euripides's tragic tale anticipates Freud's
      inquiries, exploring the fundamental link between free speech and female
      embodiment. The author suggests that psychoanalysis should claim its own
      conception of a polis as a mediated and ethical space between private and public
      spheres, between body and mind, and between speaking and listening communities.

PMID- 26198600
TI  - Incidence of hypoxia and related events detected by pulse oximeters provided by
      the Lifebox Foundation in the maternity unit at Sylvanus Olympio University
      Teaching Hospital, Togo.
AB  - In recent decades anesthesia safety has not been improved in low-income
      countries. This prospective audit describes the incidence of hypoxia and related
      events detected among a cohort of patients undergoing surgery in the maternity
      unit at Sylvanus Olympio University Teaching Hospital, Togo, West Africa, by
      using pulse oximeters donated by the Lifebox Foundation. The Lifebox oximeter
      enables early detection of hypoxia for patients undergoing surgery before
      irreversible damage occurs. Pulse oximetry is cost-effective intervention and
      should be more accessible in all operating rooms of this type. 

PMID- 26198603
TI  - NARCISSISTIC DEFENSES IN THE DISTORTION OF FREE ASSOCIATION AND THEIR UNDERLYING
      ANXIETIES.
AB  - This paper examines particular distortions in the process of free association
      characteristics of patients with narcissistic personality disorders. The author
      proposes that the dominant narcissistic transference developments typical of the
      early and middle phases of the analytic treatment of these patients are reflected
      in these distortions of free association. This paper gathers the various patterns
      that these defensive distortions present, along with technical interventions
      geared to deal with them. 

PMID- 26198604
TI  - THE OBJECT-PRESERVING FUNCTION OF SADOMASOCHISM.
AB  - The terms sadism, masochism, and sadomasochism seem to have become increasingly,
      if loosely, associated with aggression in psychoanalytic discourse. This is due
      in part to the fact that Freud's changing ideas generated confusion about the
      relative contributions of libido and aggression. The author reviews Freud's
      variable usage and offers a clinical vignette to illustrate the importance of
      noticing how sadomasochism may maintain a tie to the object by controlling it.
      The author offers a developmental speculation for the role reversibility typical
      of sadomasochistic manifestations. He closes with a comment on the role of
      sadomasochistic aims in adult sexual perversion. 

PMID- 26198605
TI  - INSIGHT AGONISTES: A READING OF SOPHOCLES'S OEDIPUS THE KING.
AB  - In this reading of Sophocles's Oedipus the King, the author suggests that insight
      can be thought of as the main protagonist of the tragedy. He personifies this
      depiction of insight, calling it Insight Agonistes, as if it were the sole
      conflicted character on the stage, albeit masquerading at times as several other
      characters, including gods, sphinxes, and oracles. This psychoanalytic reading of
      the text lends itself to an analogy between psychoanalytic process and
      Sophocles's tragic hero. The author views insight as always transgressing
      against, always at war with a conservative, societal, or intrapsychic chorus of
      structured elements. A clinical vignette is presented to illustrate this view of
      insight. 

PMID- 26198606
TI  - THE USE AND ABUSE OF OMNIPOTENCE IN THE JOURNEY OF THE HERO.
AB  - The author uses Joseph Campbell's (1949) account of the "Journey of the Hero" to
      examine a sequence of stages in which the hero must first use omnipotence in
      order to embark on an adventure, and then relinquish it in order to return to the
      ordinary world. The author detects parallels to this theme in descriptions of the
      fate of Lucifer in Milton's Paradise Lost (1674), and in the development of
      toddlers as described in Mahler's (1972) observations on separation
      individuation. Finally, he traces a similar process in clinical material drawn
      from near the end of a patient's analysis. 

PMID- 26198607
TI  - ON LOVE AND MELANCHOLIA IN MARGUERITE DURAS'S AUTOFICTION.
AB  - In the Durassian melancholic atmosphere, past and present, fantasy and reality
      come together as one. This paper addresses the themes of love and destruction in
      Marguerite Duras's life that pervade her oeuvre, allowing us to discern a
      melancholic structure within her autofiction. Writing down her melancholia--the
      impossible mourning of a loved object--Duras captures nothingness and loss--in
      order not to die of love. In a constant exchange with her readers, she searches
      for herself and delivers herself to her readers. This renewable creative process
      of writing enables her to engage in an ongoing experience of identity
      reconstruction, in a way similar to the patient in psychoanalysis re-creating
      his/her life's fiction.

PMID- 26198617
TI  - Impact of Botulinum Neurotoxin Pyloric Injection During Laparoscopic Sleeve
      Gastrectomy on Postoperative Gastric Leak: a Clinical Randomized Study.
AB  - BACKGROUND: The most frequent and most feared complication after laparoscopic
      sleeve gastrectomy (LSG) is gastric leak (GL). We hypothesize that botulinum
      neurotoxin (botulinum type A (BTX-A)) injection into the pyloric sphincter muscle
      at the time of operation may decrease the risk of postoperative GL. METHODS:
      Consecutive patients with morbid obesity (MO) treated by LSG were enrolled.
      Patients were randomly allocated into two groups: group I (intrapyloric BTX-A
      injection was performed) and group II (no injection was performed). The primary
      outcome measure was number of patients developing GL. Secondary outcome measures
      were percent of excess weight loss, postoperative complications, and their
      management. RESULTS: One hundred and fifteen patients (86 (74.8 %) females) were
      randomized into two groups of 57 patients (group I) and 58 patients (group II).
      Four patients in group II developed GL versus no patient in group I (P = 0.04).
      Ten patients in group I and two in group II developed refractory epigastric pain
      (P = 0.01). Other complication rates were comparable for both groups. Mean
      preoperative BMI of patients in both groups had significantly decreased from
      54.64 +/- 6.82 to 42.99 +/- 5.3 at 6 months and to 39.09 +/- 5.14 at 12 months (P
      < 0.001). CONCLUSIONS: LSG is an effective, safe, and minimally invasive
      procedure for treatment of MO. No patient in whom pyloric BTX-A injection was
      performed developed postoperative GL versus four patients in whom injection was
      not performed. The difference in GL rate was statistically significant, thus
      favoring the use of pyloric BTX-A injection during LSG.

PMID- 26198618
TI  - DNA Methylation and Hydroxymethylation Levels in Relation to Two Weight Loss
      Strategies: Energy-Restricted Diet or Bariatric Surgery.
AB  - BACKGROUND: Weight loss can be influenced by genetic factors and epigenetic
      mechanisms that participate in the regulation of body weight. This study aimed to
      investigate whether the weight loss induced by two different obesity treatments
      (energy restriction or bariatric surgery) may affect global DNA methylation (LINE
      1) and hydroxymethylation profile, as well as the methylation patterns in
      inflammatory genes. METHODS: This study encompassed women from three differents
      groups: 1. control group (n = 9), normal weight individuals; 2. energy
      restriction group (n = 22), obese patients following an energy-restricted
      Mediterranean-based dietary treatment (RESMENA); and 3. bariatric surgery group
      (n = 14), obese patients underwent a hypocaloric diet followed by bariatric
      surgery. Anthropometric measurements and 12-h fasting blood samples were
      collected before the interventions and after 6 months. Lipid and glucose
      biomarkers, global hydroxymethylation (by ELISA), LINE-1, SERPINE-1, and IL-6 (by
      MS-HRM) methylation levels were assessed in all participants. RESULTS: Baseline
      LINE-1 methylation was associated with serum glucose levels whereas baseline
      hydroxymethylation was associated with BMI, waist circumference, total
      cholesterol, and triglycerides. LINE-1 and SERPINE-1 methylation levels did not
      change after weight loss, whereas IL-6 methylation increased after energy
      restriction and decreased in the bariatric surgery group. An association between
      SERPINE-1 methylation and weight loss responses was found. CONCLUSIONS: Global
      DNA methylation and hydroxymethylation might be biomarkers for obesity and
      associated comorbidities. Depending on the obesity treatment (diet or surgery),
      the DNA methylation patterns behave differently. Baseline SERPINE-1 methylation
      may be a predictor of weight loss values after bariatric surgery.

PMID- 26198619
TI  - Microfluidic Production of Alginate Hydrogel Particles for Antibody Encapsulation
      and Release.
AB  - Owing to their biocompatibility and reduced side effects, natural polymers
      represent an attractive choice for producing drug delivery systems. Despite few
      successful examples, however, the production of monodisperse biopolymer-based
      particles is often hindered by high viscosity of polymer fluids. In this work, we
      present a microfluidic approach for production of alginate-based particles
      carrying encapsulated antibodies. We use a triple-flow micro-device to induce
      hydrogel formation inside droplets before their collection off-chip. The fast
      mixing and gelation process produced alginate particles with a unique biconcave
      shape and dimensions of the mammalian cells. We show slow and fast dissolution of
      particles in different buffers and evaluate antibody release over time. 

PMID- 26198620
TI  - Polymorphisms in genes of respiratory control and sudden infant death syndrome.
AB  - Sudden infant death syndrome (SIDS) is a multifactorial syndrome and assumingly,
      among other mechanisms, a deficit in respiratory control leads to a failure of
      arousal and autoresuscitation when the child is challenged by a stressful
      homeostatic event, e.g., hypoxia. We hypothesize that genetic polymorphisms
      involved in respiratory control mediated in the medulla oblongata contribute to
      SIDS. Therefore, a total of 366 SIDS cases and 421 controls were genotyped for 48
      SNPs in 41 candidate genes. Genotyping was performed using Fluidigm nanofluidic
      technology. Results were obtained for 356 SIDS and 406 controls and 38 SNPs.
      After correction for multiple testing, one SNP retained a nominally significant
      association with seasonal SIDS: rs1801030 in the phenol sulfotransferase 1A1 gene
      (subgroup: death occurring during summer). A borderline association could be also
      observed for rs563649 in the opioid receptor MU1 gene in a recessive model
      (subgroup: death occurring during autumn). As a conclusion, although these data
      suggest two SNPs to be associated with different subgroups of SIDS cases, none of
      them can fully explain the SIDS condition, consistent with its multifactorial
      etiology. Given the great complexity of respiratory control and our initial
      findings reported here, we believe it is worthwhile to further investigate genes
      involved in the respiratory system. 

PMID- 26198623
TI  - Medical Students' Attitudes Towards Health Care for People with Intellectual
      Disabilities: A Qualitative Study.
AB  - BACKGROUND: People with intellectual disabilities experience serious health
      inequalities (e.g. they die younger than people without intellectual
      disabilities). Medical students' attitudes towards health care for this
      population warrant empirical attention because, as tomorrow's doctors, they will
      affect the health inequalities that people with intellectual disabilities
      experience. MATERIALS AND METHODS: This study investigated these attitudes by
      interviewing 17 medical students about medical students' attitudes towards people
      with intellectual disabilities and thematically analysing resultant qualitative
      data. RESULTS: Key themes were identified, such as medical students' worries
      about working with patients with intellectual disabilities, and their wish for
      more medical teaching on, and direct experience with, this patient group.
      CONCLUSIONS: This study suggests that medical schools need to better prepare
      medical students for their roles as providers of health care to people with
      intellectual disabilities by, for example, enhancing their attitudes towards
      health care for people with intellectual disabilities.

PMID- 26198622
TI  - Ultrasmall Gold Nanorod Vesicles with Enhanced Tumor Accumulation and Fast
      Excretion from the Body for Cancer Therapy.
AB  - A new kind of ultrasmall dissociable AuNR@PEG/PLGA vesicles (~60 nm) (AuNR = gold
      nanorod; PEG = poly(ethylene glycol); PLGA = poly(lactic-co-glycolic acid))
      assembled from small AuNRs (dimension: ~8 nm * 2 nm) is reported. They exhibit
      several striking features: prolonged circulation and prominent tumor
      accumulation; rapid excretion from the body as AuNR@PEG after therapy; enhanced
      photoacoustic and photo thermal properties; and high photothermal cancer therapy
      efficacy. 

PMID- 26198624
TI  - Effect of recurrent onabotulinum toxin A injection into the salivary glands: An
      ultrasound measurement.
AB  - OBJECTIVES/HYPOTHESIS: Onabotulinum toxin A (OBTXA) injection is a well
      established therapeutic option for the management of drooling. Many of the
      children treated undertake repeated injections every 3 to 6 months. We aimed to
      assess quantitative salivary gland changes via ultrasound imaging after
      intraglandular injection of OBTXA for sialorrhea treatment in children, as a
      method that suggests permanent changes in glandular size can cause a decrease in
      functionality or atrophy. STUDY DESIGN: Case-control study. METHODS: The parotid
      and submandibular glands of 22 patients with sialorrhea with previous repetitive
      OBTXA treatments were measured via ultrasound. These were compared with a control
      group of 38 healthy children. RESULTS: A total of 60 patients were included in
      the study (38 boys, 22 females). Body mass index, sex, and age were defined as
      confounders. The mean age was 7 years (standard deviation [SD] +/-2.3 years) and
      9 years (SD +/-3.8 years) for treatment and control groups, respectively. There
      were no postinjection complications. We found significant decrease in the size
      dimensions (surface area and depth) of both submandibular glands and one parotid
      gland in the treatment group (P < .05). Significant smaller anterior-posterior
      dimension of the submandibular glands (P < .01) was also found. CONCLUSIONS: The
      chronic use of intraglandular OBTXA reduced the size of the salivary glands
      measured ultrasonographically. Results were correlated with clinical outcomes.
      Pathological studies should be done to correlate whether ultrasound changes
      result in atrophy or apoptosis of the glands. LEVEL OF EVIDENCE: 3b

PMID- 26198625
TI  - Targeting clinical outcomes: Endovascular simulation improves diagnostic coronary
      angiography skills.
AB  - OBJECTIVE: The purpose of this study is to determine the effects of simulation
      based medical education (SBME) on the skills required to perform coronary
      angiography in the cardiac catheterization laboratory. BACKGROUND: Cardiovascular
      fellows commonly learn invasive procedures on patients. Because this approach is
      not standardized, it can result in inconsistent skill acquisition through
      exclusion of concepts and skills. Also, the learning curve varies between
      trainees yielding variability in skill acquisition. Therefore, coronary
      angiography skills are an excellent target for SBME in an environment in which
      direct patient care is not jeopardized. METHODS: From January 2013 to June 2013,
      14 cardiovascular fellows entering the cardiac catheterization laboratory at a
      tertiary care teaching hospital were tested on an endovascular simulator to
      assess baseline skills. All fellows subsequently underwent didactic teaching and
      preceptor-lead training on the endovascular simulator. Topics included basic
      catheterization skills and a review of catheterization laboratory systems.
      Following training, all fellows underwent a post-training assessment on the
      endovascular simulator. Paired t tests were used to compare items on the skills
      checklist and simulator defined variables. RESULTS: Cardiovascular fellows scored
      significantly higher on a diagnostic coronary angiography skills checklist
      following SBME using an endovascular simulator. The mean pretest score was 66.6%
      (SD = 9.7%) compared to 86.0% (SD = 6.3%) following simulator training (P <
      0.001). Additional findings include significant reduction in procedure time and
      use of cine-fluoroscopy at posttest. CONCLUSIONS: SBME significantly improved
      cardiovascular fellows' performance of simulated coronary angiography skills.
      Standardized simulation-based education is a valuable adjunct to traditional
      clinical education for cardiovascular fellows.

PMID- 26198626
TI  - An integrated mathematical model of the cardiovascular and respiratory systems.
AB  - This study presents a lumped model for the human cardiorespiratory system.
      Specifically, we incorporate a sophisticated gas dissociation and transport
      system to a fully integrated cardiovascular and pulmonary model. The model
      provides physiologically consistent predictions in terms of hemodynamic variables
      such as pressure, flow rate, gas partial pressures, and pH. We perform numerical
      simulations to evaluate the behavior of the partial pressures of oxygen and
      carbon dioxide in different vascular and pulmonary compartments. For this, we
      design the rest condition with low oxygen requirements and carbon dioxide
      production and exercise conditions with high oxygen demand and carbon dioxide
      production. Furthermore, model sensitivity to more relevant model parameters is
      studied. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26198627
TI  - Reuse of insulin pens among multiple patients at 2 Veterans Affairs medical
      centers.
AB  - OBJECTIVE: To determine whether reuse of insulin pens among multiple patients
      resulted in transmission of bloodborne pathogens (BBP). DESIGN: Retrospective
      cohort study. SETTING: Two Veterans Affairs medical centers. PATIENTS: Veterans
      who received insulin via insulin pens from 2010 to 2013. METHODS Patients were
      identified through electronic health records, notified of possible exposure, and
      serotested for human immunodeficiency virus, hepatitis C virus (HCV), and
      hepatitis B virus. Newly discovered case patients were assessed in relation to
      potential proximate patients to determine viral strain relatedness by HCV
      envelope (env) gene sequencing. RESULTS: Of 1,791 hospitalized veterans who
      received insulin via insulin pen, 1,155 were tested for at least 1 viral
      infection after exposure. Of these, 67 patients were newly diagnosed with 1 or
      more viral BBPs. For human immunodeficiency virus and hepatitis B virus no
      additional strain testing of case or proximate patients was possible; 8 HCV cases
      and 45 proximates (40 unique patients; 5 patients were positive for 2 genotypes)
      were identified as needing strain testing. Only 3 cases and their 19 proximates
      had samples available for further testing. None of the 26 remaining proximate
      patients had blood available for further testing. Median genetic distance between
      the HCV env sequences of those available for additional testing ranged from 14%
      to 24%, indicating nonrelatedness. CONCLUSIONS: Our investigation revealed that
      exposure to insulin pen reuse did not result in HCV transmission among patients
      who had viral genetic analysis performed. Analysis for any additional potential
      transmission of blood-borne pathogens was limited by the available samples.

PMID- 26198628
TI  - The Association Between Disaster Vulnerability and Post-disaster Psychosocial
      Service Delivery Across Europe.
AB  - This study confirms that the developmental stage of post-disaster psychosocial
      support planning and delivery systems in Europe is associated with countries'
      level of disaster vulnerability. Lower vulnerability is accompanied by more
      evolved planning and delivery systems. Countries in north, west and central
      regions have more developed planning and delivery systems and lower vulnerability
      levels than those in the south, southeast and east. The highest proportion of
      variance in vulnerability is located at the regional level, most of the variance
      in planning and delivery systems is at the individual level. Possible
      implications and chances for the optimization of psychosocial services are
      discussed.

PMID- 26198629
TI  - Protein kinase CK2 interacts at the neuromuscular synapse with Rapsyn, Rac1, 14-3
      3gamma, and Dok-7 proteins and phosphorylates the latter two.
AB  - Previously, we demonstrated that the protein kinase CK2 associates with and
      phosphorylates the receptor tyrosine kinase MuSK (muscle specific receptor
      tyrosine kinase) at the neuromuscular junction (NMJ), thereby preventing
      fragmentation of the NMJs (Cheusova, T., Khan, M. A., Schubert, S. W., Gavin, A.
      C., Buchou, T., Jacob, G., Sticht, H., Allende, J., Boldyreff, B., Brenner, H.
      R., and Hashemolhosseini, S. (2006) Genes Dev. 20, 1800-1816). Here, we asked
      whether CK2 interacts with other proteins involved in processes at the NMJ, which
      would be consistent with the previous observation that CK2 appears enriched at
      the NMJ. We identified the following proteins to interact with protein kinase
      CK2: (a) the alpha and beta subunits of the nicotinic acetylcholine receptors
      with weak interaction, (b) dishevelled (Dsh), and (c) another four proteins,
      Rapsyn, Rac1, 14-3-3gamma, and Dok-7, with strong interaction. CK2 phosphorylated
      14-3-3gamma at serine residue 235 and Dok-7 at several serine residues but does
      not phosphorylate Rapsyn or Rac1. Furthermore, phosphomimetic Dok-7 mutants
      aggregated nicotinic acetylcholine receptors in C2C12 myotubes with significantly
      higher frequency than wild type Dok-7. Additionally, we mapped the interacting
      epitopes of all four binding partners to CK2 and thereby gained insights into the
      potential role of the CK2/Rapsyn interaction. 

PMID- 26198630
TI  - Phosphorylation-dependent changes in nucleotide binding, conformation, and
      dynamics of the first nucleotide binding domain (NBD1) of the sulfonylurea
      receptor 2B (SUR2B).
AB  - The sulfonylurea receptor 2B (SUR2B) forms the regulatory subunit of ATP
      sensitive potassium (KATP) channels in vascular smooth muscle. Phosphorylation of
      the SUR2B nucleotide binding domains (NBD1 and NBD2) by protein kinase A results
      in increased channel open probability. Here, we investigate the effects of
      phosphorylation on the structure and nucleotide binding properties of NBD1.
      Phosphorylation sites in SUR2B NBD1 are located in an N-terminal tail that is
      disordered. Nuclear magnetic resonance (NMR) data indicate that phosphorylation
      of the N-terminal tail affects multiple residues in NBD1, including residues in
      the NBD2-binding site, and results in altered conformation and dynamics of NBD1.
      NMR spectra of NBD1 lacking the N-terminal tail, NBD1-DeltaN, suggest that
      phosphorylation disrupts interactions of the N-terminal tail with the core of
      NBD1, a model supported by dynamic light scattering. Increased nucleotide binding
      of phosphorylated NBD1 and NBD1-DeltaN, compared with non-phosphorylated NBD1,
      suggests that by disrupting the interaction of the NBD core with the N-terminal
      tail, phosphorylation also exposes the MgATP-binding site on NBD1. These data
      provide insights into the molecular basis by which phosphorylation of SUR2B NBD1
      activates KATP channels. 

PMID- 26198631
TI  - Regulation of Yin Yang 1 by Tyrosine Phosphorylation.
AB  - Yin Yang 1 (YY1) is a member of the GLI-Kruppel class of DNA and RNA binding
      transcription factors that can either activate or repress gene expression during
      cell growth, differentiation, and embryogenesis. Although much is known about YY1
      interacting proteins and the target promoters regulated by YY1, much less is
      known about YY1 regulation through post-translational modifications. In this
      study we show that YY1 is tyrosine-phosphorylated in multiple cell types. Using a
      combination of pharmacological inhibition, kinase overexpression, and kinase
      knock-out studies, we demonstrate that YY1 is a target of multiple Src family
      kinases in vitro and in vivo. Moreover, we have identified multiple sites of YY1
      phosphorylation and analyzed the effect of phosphorylation on the activity of YY1
      responsive retroviral and cellular promoters. Phosphorylation of tyrosine 383
      interferes with DNA and RNA binding, leading to the down-regulation of YY1
      activity. Finally, we provide the first evidence that YY1 is a downstream target
      of epidermal growth factor receptor signaling in vivo. Taken together, the
      identification of YY1 as a target of Src family kinases provide key insights into
      the inhibitory role of tyrosine kinases in modulating YY1 activity. 

PMID- 26198632
TI  - A structural snapshot of type II pilus formation in Streptococcus pneumoniae.
AB  - Pili are fibrous appendages expressed on the surface of a vast number of
      bacterial species, and their role in surface adhesion is important for processes
      such as infection, colonization, andbiofilm formation. The human pathogen
      Streptococcus pneumoniae expresses two different types of pili, PI-1 and PI-2,
      both of which require the concerted action of structural proteins and sortases
      for their polymerization. The type PI-1 streptococcal pilus is a complex, well
      studied structure, but the PI-2 type, present in a number of invasive
      pneumococcal serotypes, has to date remained less well understood. The PI-2 pilus
      consists of repeated units of a single protein, PitB, whose covalent association
      is catalyzed by cognate sortase SrtG-1 and partner protein SipA. Here we report
      the high resolution crystal structures of PitB and SrtG1 and use molecular
      modeling to visualize a "trapped" 1:1 complex between the two molecules. X-ray
      crystallography and electron microscopy reveal that the pneumococcal PI-2
      backbone fiber is formed by PitB monomers associated in head-to-tail fashion and
      that short, flexible fibers can be formed even in the absence of coadjuvant
      proteins. These observations, obtained with a simple pilus biosynthetic system,
      are likely to be applicable to other fiber formation processes in a variety of
      Gram-positive organisms. 

PMID- 26198633
TI  - Generation and preclinical characterization of an NKp80-Fc fusion protein for
      redirected cytolysis of natural killer (NK) cells against leukemia.
AB  - The capacity of natural killer (NK) cells to mediate Fc receptor-dependent
      effector functions, such as antibody-dependent cellular cytotoxicity (ADCC),
      largely contributes to their clinical application. Given that activation-induced
      C-type lectin (AICL), an identified ligand for the NK-activating receptor NKp80,
      is frequently highly expressed on leukemia cells, the lack of therapeutic AICL
      specific antibodies limits clinical application. Here we explore a strategy to
      reinforce NK anti-leukemia reactivity by combining targeting AICL-expressing
      leukemia cells with the induction of NK cell ADCC using NKp80-Fc fusion proteins.
      The NKp80-Fc fusion protein we generated bound specifically to leukemia cells in
      an AICL-specific manner. Cell binding assays between NK and leukemia cells showed
      that NKp80-Fc significantly increased NK target cell conjugation. In functional
      analyses, treatment with NKp80-Fc clearly induced the ADCC effect of NK cells.
      NKp80-Fc not only promoted NK-mediated leukemia cell apoptosis in the early stage
      of cell conjugation but also enhanced NK cell degranulation and cytotoxicity
      activity in the late stage. The bifunctional NKp80-Fc could redirect NK cells
      toward leukemia cells and triggered NK cell killing in vitro. Moreover, NKp80-Fc
      enhanced the lysis of NK cells against tumors in leukemia xenograft non-obese
      diabetic/severe combined immunodeficiency mice. Taken together, our results
      demonstrate that NKp80-Fc potently amplifies NK cell anti-leukemia effects in
      vitro and in vivo through induction of the NK cell ADCC effect. This method could
      potentially be useful for molecular targeted therapy, and the fusion proteins may
      be a promising drug for immunotherapy of leukemia. 

PMID- 26198634
TI  - Modulation of Glucagon Receptor Pharmacology by Receptor Activity-modifying
      Protein-2 (RAMP2).
AB  - The glucagon and glucagon-like peptide-1 (GLP-1) receptors play important,
      opposing roles in regulating blood glucose levels. Consequently, these receptors
      have been identified as targets for novel diabetes treatments. However, drugs
      acting at the GLP-1 receptor, although having clinical efficacy, have been
      associated with severe adverse side-effects, and targeting of the glucagon
      receptor has yet to be successful. Here we use a combination of yeast reporter
      assays and mammalian systems to provide a more complete understanding of glucagon
      receptor signaling, considering the effect of multiple ligands, association with
      the receptor-interacting protein receptor activity-modifying protein-2 (RAMP2),
      and the role of individual G protein alpha-subunits. We demonstrate that RAMP2
      alters both ligand selectivity and G protein preference of the glucagon receptor.
      Importantly, we also uncover novel cross-reactivity of therapeutically used GLP-1
      receptor ligands at the glucagon receptor that is abolished by RAMP2 interaction.
      This study reveals the glucagon receptor as a previously unidentified target for
      GLP-1 receptor agonists and highlights a role for RAMP2 in regulating its
      pharmacology. Such previously unrecognized functions of RAMPs highlight the need
      to consider all receptor-interacting proteins in future drug development. 

PMID- 26198635
TI  - Identification of a Novel Sequence Motif Recognized by the Ankyrin Repeat Domain
      of zDHHC17/13 S-Acyltransferases.
AB  - S-Acylation is a major post-translational modification affecting several cellular
      processes. It is particularly important for neuronal functions. This modification
      is catalyzed by a family of transmembrane S-acyltransferases that contain a
      conserved zinc finger DHHC (zDHHC) domain. Typically, eukaryote genomes encode
      for 7-24 distinct zDHHC enzymes, with two members also harboring an ankyrin
      repeat (AR) domain at their cytosolic N termini. The AR domain of zDHHC enzymes
      is predicted to engage in numerous interactions and facilitates both substrate
      recruitment and S-acylation-independent functions; however, the
      sequence/structural features recognized by this module remain unknown. The two
      mammalian AR-containing S-acyltransferases are the Golgi-localized zDHHC17 and
      zDHHC13, also known as Huntingtin-interacting proteins 14 and 14-like,
      respectively; they are highly expressed in brain, and their loss in mice leads to
      neuropathological deficits that are reminiscent of Huntington's disease. Here, we
      report that zDHHC17 and zDHHC13 recognize, via their AR domain, evolutionary
      conserved and closely related sequences of a [VIAP][VIT]XXQP consensus in SNAP25,
      SNAP23, cysteine string protein, Huntingtin, cytoplasmic linker protein 3, and
      microtubule-associated protein 6. This novel AR-binding sequence motif is found
      in regions predicted to be unstructured and is present in a number of zDHHC17
      substrates and zDHHC17/13-interacting S-acylated proteins. This is the first
      study to identify a motif recognized by AR-containing zDHHCs. 

PMID- 26198636
TI  - Deficiency in the Lipid Exporter ABCA1 Impairs Retrograde Sterol Movement and
      Disrupts Sterol Sensing at the Endoplasmic Reticulum.
AB  - Cellular cholesterol homeostasis involves sterol sensing at the endoplasmic
      reticulum (ER) and sterol export from the plasma membrane (PM). Sterol sensing at
      the ER requires efficient sterol delivery from the PM; however, the
      macromolecules that facilitate retrograde sterol transport at the PM have not
      been identified. ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol
      and phospholipid export to apolipoprotein A-I for the assembly of high density
      lipoprotein (HDL). Mutations in ABCA1 cause Tangier disease, a familial HDL
      deficiency. Several lines of clinical and experimental evidence suggest a second
      function of ABCA1 in cellular cholesterol homeostasis in addition to mediating
      cholesterol efflux. Here, we report the unexpected finding that ABCA1 also plays
      a key role in facilitating retrograde sterol transport from the PM to the ER for
      sterol sensing. Deficiency in ABCA1 delays sterol esterification at the ER and
      activates the SREBP-2 cleavage pathway. The intrinsic ATPase activity in ABCA1 is
      required to facilitate retrograde sterol transport. ABCA1 deficiency causes
      alternation of PM composition and hampers a clathrin-independent endocytic
      activity that is required for ER sterol sensing. Our finding identifies ABCA1 as
      a key macromolecule facilitating bidirectional sterol movement at the PM and
      shows that ABCA1 controls retrograde sterol transport by modulating a certain
      clathrin-independent endocytic process. 

PMID- 26198637
TI  - The Proto-oncogene Transcription Factor Ets1 Regulates Neural Crest Development
      through Histone Deacetylase 1 to Mediate Output of Bone Morphogenetic Protein
      Signaling.
AB  - The neural crest (NC) is a transient, migratory cell population that
      differentiates into a large variety of tissues including craniofacial cartilage,
      melanocytes, and peripheral nervous system. NC is initially induced at the border
      of neural plate and non-neural ectoderm by balanced regulation of multiple
      signaling pathways among which an intermediate bone morphogenetic protein (BMP)
      signaling is essential for NC formation. ets1, a proto-oncogene playing important
      roles in tumor invasion, has also been implicated in delamination of NC cells. In
      this study, we investigated Ets1 function in NC formation using Xenopus.
      Overexpression of ets1 repressed NC formation through down-regulation of BMP
      signaling. Moreover, ets1 repressed the BMP-responsive gene id3 that is essential
      for NC formation. Conversely, overexpression of id3 can partially rescue the
      phenotype of NC inhibition induced by ectopic ets1. Mechanistically, we found
      that Ets1 binds to id3 promoter as well as histone deacetylase 1, suggesting that
      Ets1 recruits histone deacetylase 1 to the promoter of id3, thereby inducing
      histone deacetylation of the id3 promoter. Thus, our studies indicate that Ets1
      regulates NC formation through attenuating BMP signaling epigenetically. 

PMID- 26198638
TI  - Saccharomyces cerevisiae Sen1 Helicase Domain Exhibits 5'- to 3'-Helicase
      Activity with a Preference for Translocation on DNA Rather than RNA.
AB  - In the yeast Saccharomyces cerevisiae, the essential nuclear helicase Sen1 is
      required for efficient termination of transcription of short noncoding RNA genes
      by RNA polymerase II. However, the mechanism by which Sen1 promotes transcription
      termination is not known. Prior biochemical studies on the Sen1 homolog from
      Schizosaccharomyces pombe showed that it can bind and unwind both DNA and RNA,
      but the S. pombe protein is not essential and has not been demonstrated to
      function in transcription. Furthermore, Sen1 from either yeast has not previously
      been expressed as a recombinant protein, due to its large molecular mass (252 kDa
      in S. cerevisiae). Here, we report the purification and characterization of the
      89-kDa S. cerevisiae Sen1 helicase domain (Sen1-HD) produced in Escherichia coli.
      Sen1-HD binds single-stranded RNA and DNA with similar affinity in the absence of
      ATP, but it binds RNA more stably than DNA in the presence of ATP, apparently due
      to a slower translocation rate on RNA. Translocation occurs in the 5' to 3'
      direction, as for the S. pombe protein. When purified from E. coli at a moderate
      salt concentration, Sen1-HD was associated with short RNAs that are enriched for
      the trinucleotide repeat (CAN)4. We propose that Sen1 binds to RNAs and prevents
      their stable pairing with DNA, consistent with in vivo studies by others showing
      increased R-loop (RNA/DNA hybrid) formation when Sen1 activity is impaired by
      mutations. Our results are consistent with a model in which Sen1 promotes
      transcription termination by resolving R-loops. 

PMID- 26198639
TI  - A Metabolic Shift toward Pentose Phosphate Pathway Is Necessary for Amyloid
      Fibril- and Phorbol 12-Myristate 13-Acetate-induced Neutrophil Extracellular Trap
      (NET) Formation.
AB  - Neutrophils are the main defense cells of the innate immune system. Upon
      stimulation, neutrophils release their chromosomal DNA to trap and kill
      microorganisms and inhibit their dissemination. These chromatin traps are termed
      neutrophil extracellular traps (NETs) and are decorated with granular and
      cytoplasm proteins. NET release can be induced by several microorganism membrane
      components, phorbol 12-myristate 13-acetate as well as by amyloid fibrils,
      insoluble proteinaceous molecules associated with more than 40 different
      pathologies among other stimuli. The intracellular signaling involved in NET
      formation is complex and remains unclear for most tested stimuli. Herein we
      demonstrate that a metabolic shift toward the pentose phosphate pathway (PPP) is
      necessary for NET release because glucose-6-phosphate dehydrogenase (G6PD), an
      important enzyme from PPP, fuels NADPH oxidase with NADPH to produce superoxide
      and thus induce NETs. In addition, we observed that mitochondrial reactive oxygen
      species, which are NADPH-independent, are not effective in producing NETs. These
      data shed new light on how the PPP and glucose metabolism contributes to NET
      formation. 

PMID- 26198640
TI  - Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-Troglitazone
      induced Apoptosis in Prostate Cancer Cells Involve AMP-activated Protein Kinase.
AB  - Prostate cancer (PCa) is one of the most frequently diagnosed cancers in men with
      limited treatment options for the hormone-resistant forms. Development of novel
      therapeutic options is critically needed to target advanced forms. Here we
      demonstrate that combinatorial treatment with the thiazolidinedione troglitazone
      (TZD) and TNF-related apoptosis-inducing ligand (TRAIL) can induce significant
      apoptosis in various PCa cells independent of androgen receptor status. Because
      TZD is known to activate AMP-activated protein kinase (AMPK), we determined
      whether AMPK is a molecular target mediating this apoptotic cascade by utilizing
      PCa cell lines stably overexpressing AMPKalpha1 dominant negative (C4-2-DN) or
      empty vector (C4-2-EV). Our results indicated a significantly higher degree of
      apoptosis with TRAIL-TZD combination in C4-2-EV cells compared with C4-2-DN
      cells. Similarly, results from a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay showed a larger reduction of viability of C4-2
      EV cells compared with C4-2-DN cells when treated with TRAIL-TZD, thus suggesting
      that C4-2-DN cells were more apoptosis-resistant. Additionally, siRNA-mediated
      knockdown of endogenous AMPKalpha1 expression showed a reduction of TRAIL-TZD
      induced apoptosis, further confirming the participation of AMPK in mediating this
      apoptosis. Apoptosis induction by this combinatorial treatment was also
      associated with a cleavage of beta-catenin that was inhibited in both C4-2-DN
      cells and those cells in which AMPKalpha1 was knocked down. In addition, time
      course studies showed an increase in pACC(S79) (AMPK target) levels coinciding
      with the time of apoptosis. These studies indicate the involvement of AMPK in
      TRAIL-TZD-mediated apoptosis and beta-catenin cleavage and suggest the
      possibility of utilizing AMPK as a therapeutic target in apoptosis-resistant
      prostate cancer. 

PMID- 26198642
TI  - Nonsteroidal anti-inflammatory drugs and bleeding risk in anticoagulated patients
      with atrial fibrillation.
AB  - Although nonsteroidal anti-inflammatory drugs (NSAIDs) have generally conferred
      increased gastrointestinal bleeding risk, the data for bleeding risks with these
      drugs in anticoagulated atrial fibrillation (AF) patients per se were much more
      limited. Recent evidence shows that concomitant use of NSAIDs in anticoagulated
      AF patients carries a real risk of serious bleeding, as well as thromboembolism.
      Thus, physicians should clearly exercise extra caution with NSAIDs in patients
      with AF, especially if they are anticoagulated. Also, AF patients with NSAIDs
      should also undergo regular clinical review, and clinicians should regularly
      reassess the need for NSAID use. Finally, as a part of regular clinical
      assessment, bleeding risk should be routinely assessed, and the HAS-BLED score is
      now recommended in many guidelines for this purpose. 

PMID- 26198643
TI  - The relationship between language proficiency and surgical length of stay
      following cardiac bypass surgery.
AB  - BACKGROUND: Anglophone nurses face the challenge of communicating health
      information to patients who do not speak or understand English. Limited English
      proficient patients are at higher risk of misinterpreting health information
      teaching. Successful recovery after coronary artery bypass graft surgery requires
      patients' engagement with healthcare professionals and active participation in
      therapies and related undertakings. Determination of whether limited English
      proficient patients undergoing coronary artery bypass graft surgery recover at
      the same pace as the general population is of interest. AIM: This study examined
      whether limited English-proficient patients had prolonged post-operative length
      of stay following coronary artery bypass graft surgery. The patients' length of
      stay with regard to a clinical pathway target was also examined. METHOD: A
      retrospective medical record review of all patients undergoing isolated coronary
      artery bypass graft surgery in a 2-year period was conducted. A screening tool
      was developed to identify limited English-proficient patients through examination
      of their medical records. RESULTS: A total of 691 of 712 (97.1%) patients met the
      inclusion criteria; 103 (14.9%) patients were identified as limited English
      proficient. The post-operative median length of stay of limited English
      proficient patients was 7 days compared with 6 days for the English-proficient
      patients (p = 0.007). Limited English-proficient patients had higher infection
      rates (29.1%) vs. English-proficient patients (16.7%) (odds ratio = 2.05 (95%
      confidence intervals 1.27-3.30)). Post-operative infection was the strongest
      predictor of length of stay and fully mediated the relationship between language
      proficiency and length of stay. CONCLUSION: When compared with English-proficient
      patients, limited English-proficient patients had greater infection rates, which
      were associated with longer length of stay. These findings warrant examination of
      the mechanisms through which post-operative infections are acquired by limited
      English-proficient patients.

PMID- 26198641
TI  - STAT3 regulated ARF expression suppresses prostate cancer metastasis.
AB  - Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is
      thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa
      patients has failed to provide therapeutic benefit. Here we show that genetic
      inactivation of Stat3 or IL-6 signalling in a Pten-deficient PCa mouse model
      accelerates cancer progression leading to metastasis. Mechanistically, we
      identify p19(ARF) as a direct Stat3 target. Loss of Stat3 signalling disrupts the
      ARF-Mdm2-p53 tumour suppressor axis bypassing senescence. Strikingly, we also
      identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A
      deletions co-occurred with high frequency in PCa metastases. In accordance, loss
      of STAT3 and p14(ARF) expression in patient tumours correlates with increased
      risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be
      prognostic markers to stratify high from low risk PCa patients. Our findings
      challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3
      inhibition. 

PMID- 26198644
TI  - Antiretroviral therapy for HIV should be started at diagnosis regardless of CD4+
      count, study concludes.

PMID- 26198645
TI  - Borderline Personality Disorder and Military Sexual Trauma: Analysis of Previous
      Traumatization and Current Psychiatric Presentation.
AB  - Military sexual trauma (MST) increases vulnerability for posttraumatic stress
      disorder (PTSD). Sexual trauma is also associated with increased risk for
      developing borderline personality disorder (BPD). Research has also documented a
      significant link between PTSD and BPD; however, there is a paucity of information
      examining this relationship among veterans with MST-related PTSD. In particular,
      we sought to examine whether comorbid BPD-PTSD compared with veterans with PTSD
      and no BPD resulted in increased PTSD and depression symptomatology. We also
      examined psychiatric, previous sexual trauma, and demographic factors to
      determine what-if any-factors were associated with comorbid BPD diagnosis. Using
      data from a recently conducted randomized clinical trial, we examined electronic
      medical records of the local Veterans Affairs Medical Center. Data from 90
      veterans with MST-related PTSD were obtained. More than 22% ( n = 20) of the
      sample had a historical diagnosis of BPD. Participants were administered measures
      to assess psychiatric symptomatology (PTSD and depression), trauma-related
      negative cognitions (NCs), and previous sexual traumatization (e.g., childhood
      and civilian sexual exposure). An analysis of variance was conducted, which found
      that veterans with comorbid MST-related PTSD and BPD had significantly greater
      PTSD criterion B (avoidance) symptoms, depressive symptomatology, and NC scores
      than participants without comorbid BPD. In addition, a binary stepwise logistic
      regression found that veterans' BPD was also positively associated with NCs about
      self and the world; however, self-blame, depression, PTSD, sociodemographic
      variables (e.g., gender, age), and previous sexual traumatizations were not
      significant predictors. Implications are discussed with regard to clinical care
      and future research directions.

PMID- 26198647
TI  - Oxidative Stress Mechanisms Do Not Discriminate between Genotoxic and
      Nongenotoxic Liver Carcinogens.
AB  - It is widely accepted that in chemical carcinogenesis different modes-of-action
      exist, e.g., genotoxic (GTX) versus nongenotoxic (NGTX) carcinogenesis. In this
      context, it has been suggested that oxidative stress response pathways are
      typical for NGTX carcinogenesis. To evaluate this, we examined oxidative stress
      related changes in gene expression, cell cycle distribution, and (oxidative) DNA
      damage in human hepatoma cells (HepG2) exposed to GTX-, NGTX-, and
      noncarcinogens, at multiple time points (4-8-24-48-72 h). Two GTX (azathriopine
      (AZA) and furan) and two NGTX (tetradecanoyl-phorbol-acetate, (TPA) and
      tetrachloroethylene (TCE)) carcinogens as well as two noncarcinogens (diazinon
      (DZN, d-mannitol (Dman)) were selected, while per class one compound was deemed
      to induce oxidative stress and the other not. Oxidative stressors AZA, TPA, and
      DZN induced a 10-fold higher number of gene expression changes over time compared
      to those of furan, TCE, or Dman treatment. Genes commonly expressed among AZA,
      TPA, and DZN were specifically involved in oxidative stress, DNA damage, and
      immune responses. However, differences in gene expression between GTX and NGTX
      carcinogens did not correlate to oxidative stress or DNA damage but could instead
      be assigned to compound-specific characteristics. This conclusion was underlined
      by results from functional readouts on ROS formation and (oxidative) DNA damage.
      Therefore, oxidative stress may represent the underlying cause for increased risk
      of liver toxicity and even carcinogenesis; however, it does not discriminate
      between GTX and NGTX carcinogens. 

PMID- 26198646
TI  - Obstructive sleep apnea-related symptoms in Japanese people with Down syndrome.
AB  - This study evaluated the prevalence of obstructive sleep apnea-related symptoms
      and assessed the relationship with obesity or unusual sleep postures in Down
      syndrome patients in Japan. We obtained the demographic characteristics, sleep
      postures, and obstructive sleep apnea-related symptoms experienced by 90 people
      as reported by their caregivers. Although 71% reported snoring and 59% arousals,
      obstructive sleep apnea-related symptoms were not significantly different between
      obese and non-obese participants. The youngest age group had the fewest
      obstructive sleep apnea-related symptoms, especially symptoms of snoring. The
      odds for arousal, nocturia, and apnea tended to be higher in the unusual sleep
      postures group. Unusual sleep postures were most frequent in the group 6-15 years
      of age. People with Down syndrome might sleep in unusual postures to avoid upper
      airway obstruction caused by other anatomical factors. For nurses and other
      health professionals working in mainstream service, it is important to screen all
      persons with Down syndrome for symptoms suggestive of obstructive sleep apnea,
      particularly those six years of age and older, and to refer them for further
      evaluation for sleep disorders. 

PMID- 26198648
TI  - Detection of a novel variant of HLA-B*07, HLA-B*07:249, in a Taiwanese unrelated
      hematopoietic stem cell donor.
AB  - One nucleotide replacement at residue 398 of HLA-B*07:05:01 or HLA-B*07:06
      results in a novel allele, HLA-B*07:249. 

PMID- 26198649
TI  - Response evaluation of the neck in oropharyngeal cancer: Value of magnetic
      resonance imaging and influence of p16 in selecting patients for post
      radiotherapy neck dissection.
AB  - BACKGROUND: Residual neck disease after radiotherapy in advanced oropharyngeal
      squamous cell carcinoma (OPSCC) is associated with increased mortality, and some
      patients may benefit from post-radiotherapy neck dissection (PRND). The aim of
      the present study was to assess the value of magnetic resonance imaging (MRI) and
      other clinical characteristics in selecting patients for PRND. MATERIALS AND
      METHODS: Retrospective cohort study. Consecutive patients with N+ OPSCC were
      included. Medical records, pathology reports and imaging reports were reviewed.
      Pre- and post-therapeutic imaging was re-evaluated. RESULTS: A total of 100
      consecutive patients from a three-year period were included. Neck response was
      evaluated with MRI two months after treatment. Sixty patients were suspicious for
      residual neck disease, and were offered surgery; seven of these patients had
      histologic evidence of carcinoma. Cumulative neck failure after three years was
      14% (8.4-24%), and did not differ significantly among patients with positive
      compared to negative MRI (radiologist's initial description; p = 0.47, log-rank
      test). Applying neck failure as gold standard, sensitivity and specificity of MRI
      was 69% and 41%, respectively; positive and negative predictive value was 15% and
      90%. Patients with p16 + disease had significantly larger lymph nodes after
      treatment, and imaging based on lymph node size resulted in many false positives.
      Analysis of receiver operating characteristic curves in 191 individual lymph
      nodes showed that a short axis >= 10 mm should be classified as suspicious.
      Furthermore, T-stage and p16-status were associated with increased risk of neck
      recurrence. Salvage was successful in four patients with early detected nodal
      recurrence. CONCLUSION: These results suggest that lymph node size, T-stage and
      p16 status could be used in selecting patients for PRND in OPSCC. Yet, early
      anatomical imaging may be inappropriate for evaluating neck response in patients
      with p16 + disease as enlarged lymph nodes often do not indicate residual neck
      disease.

PMID- 26198650
TI  - Cost calculation: a necessary step towards widespread adoption of advanced
      radiotherapy technology.
AB  - Radiotherapy costs are an often underestimated component of the economic
      assessment of new radiotherapy treatments and technologies. That the radiotherapy
      budget only consumes a finite part of the total cancer and healthcare budget does
      not relieve us from our responsibility to balance the extra costs to the
      additional benefits of new, more advanced, but typically also more expensive
      treatments we want to deliver. Yet, in contrast to what is the case for oncology
      drugs, literature evidence remains limited, as well for economic evaluations
      comparing new radiotherapy interventions as for cost calculation studies. Even
      more cumbersome, the available costing studies in the field of radiotherapy fail
      to accurately capture the real costs of our treatments due to the large variation
      in cost inputs, in scope of the analysis, in costing methodology. And this is not
      trivial. Accurate resource cost accounting lays the basis for the further steps
      in health technology assessment leading to radiotherapy investments and
      reimbursement, at the local, the national and the worldwide level. In the current
      paper we review some evidence from the existing costing literature and discuss
      how such data can be used to support reimbursement setting and investment cases
      for new radiotherapy equipment and infrastructure. 

PMID- 26198651
TI  - Respiratory gating based on internal electromagnetic motion monitoring during
      stereotactic liver radiation therapy: First results.
AB  - BACKGROUND: Intrafraction motion may compromise the target dose in stereotactic
      body radiation therapy (SBRT) of tumors in the liver. Respiratory gating can
      improve the treatment delivery, but gating based on an external surrogate signal
      may be inaccurate. This is the first paper reporting on respiratory gating based
      on internal electromagnetic monitoring during liver SBRT. MATERIAL AND METHODS:
      Two patients with solitary liver metastases were treated with respiratory-gated
      SBRT guided by three implanted electromagnetic transponders. The treatment was
      delivered in end-exhale with beam-on when the centroid of the three transponders
      deviated less than 3 mm [left-right (LR) and anterior-posterior (AP) directions]
      and 4mm [cranio-caudal (CC)] from the planned position. For each treatment
      fraction, log files were used to determine the transponder motion during beam-on
      in the actual gated treatments and in simulated treatments without gating. The
      motion was used to reconstruct the dose to the clinical target volume (CTV) with
      and without gating. The reduction in D95 (minimum dose to 95% of the CTV)
      relative to the plan was calculated for both treatment courses. RESULTS: With
      gating the maximum course mean (standard deviation) geometrical error in any
      direction was 1.2 mm (1.8 mm). Without gating the course mean error would mainly
      increase for Patient 1 [to -2.8 mm (1.6 mm) (LR), 7.1 mm (5.8 mm) (CC), -2.6 mm
      (2.8mm) (AP)] due to a large systematic cranial baseline drift at each fraction.
      The errors without gating increased only slightly for Patient 2. The reduction in
      CTV D95 was 0.5% (gating) and 12.1% (non-gating) for Patient 1 and 0.3% (gating)
      and 1.7% (non-gating) for Patient 2. The mean duty cycle was 55%. CONCLUSION:
      Respiratory gating based on internal electromagnetic motion monitoring was
      performed for two liver SBRT patients. The gating added robustness to the dose
      delivery and ensured a high CTV dose even in the presence of large intrafraction
      motion.

PMID- 26198652
TI  - Cone beam computed tomography guided treatment delivery and planning verification
      for magnetic resonance imaging only radiotherapy of the brain.
AB  - BACKGROUND: Radiotherapy based on MRI only (MRI-only RT) shows a promising
      potential for the brain. Much research focuses on creating a pseudo computed
      tomography (pCT) from MRI for treatment planning while little attention is often
      paid to the treatment delivery. Here, we investigate if cone beam CT (CBCT) can
      be used for MRI-only image-guided radiotherapy (IGRT) and for verifying the
      correctness of the corresponding pCT. MATERIAL AND METHODS: Six patients
      receiving palliative cranial RT were included in the study. Each patient had
      three-dimensional (3D) T1W MRI, a CBCT and a CT for reference. Further, a pCT was
      generated using a patch-based approach. MRI, pCT and CT were placed in the same
      frame of reference, matched to CBCT and the differences noted. Paired pCT-CT and
      pCT-CBCT data were created in bins of 10 HU and the absolute difference
      calculated. The data were converted to relative electron densities (RED) using
      the CT or a CBCT calibration curve. The latter was either based on a CBCT phantom
      (phan) or a paired CT-CBCT population (pop) of the five other patients. RESULTS:
      Non-significant (NS) differences in the pooled CT-CBCT, MRI-CBCT and pCT-CBCT
      transformations were noted. The largest deviations from the CT-CBCT reference
      were < 1 mm and 1 degrees . The average median absolute error (MeAE) in HU was
      184 +/- 34 and 299 +/- 34 on average for pCT-CT and pCT-CBCT, respectively, and
      was significantly different (p < 0.01) in each patient. The average MeAE in RED
      was 0.108 +/- 0.025, 0.104 +/- 0.011 and 0.099 +/- 0.017 for pCT-CT, pCT-CBCT
      phan (p < 0.01 on 2 patients) and pCT-CBCT pop (NS), respectively. CONCLUSIONS:
      CBCT can be used for patient setup with either MRI or pCT as reference. The
      correctness of pCT can be verified from CBCT using a population-based calibration
      curve in the treatment geometry.

PMID- 26198653
TI  - Implementation of volumetric modulated arc therapy for rectal cancer: Pitfalls
      and challenges.

PMID- 26198654
TI  - Comparing cone-beam CT intensity correction methods for dose recalculation in
      adaptive intensity-modulated photon and proton therapy for head and neck cancer.
AB  - BACKGROUND: Adaptive intensity-modulated photon and proton radiotherapy (IMRT and
      IMPT) of head and neck (H&N) cancer requires frequent three-dimensional (3D) dose
      calculation. We compared two approaches for dose recalculation on the basis of
      intensity-corrected cone-beam (CB) x-ray computed tomography (CT) images.
      MATERIAL AND METHODS: For nine H&N tumor patients, virtual CTs (vCT) were
      generated by deformable image registration of the planning CT (pCT) to the CBCT.
      The second intensity correction approach used population-based lookup tables for
      scaling CBCT intensities to the pCT HU range (CBCTLUT). IMRT and IMPT plans were
      generated with a commercial treatment planning system. Dose recalculations on vCT
      and CBCTLUT were analyzed using a (3%, 3 mm) gamma-index analysis and comparison
      of normal tissue and tumor dose/volume parameters. A replanning CT (rpCT)
      acquired within three days of the CBCT served as reference. Single field uniform
      dose (SFUD) proton plans were created and recalculated on vCT and CBCTLUT for
      proton range comparison. RESULTS: Dose/volume parameters showed minor differences
      between rpCT, vCT and CBCTLUT in IMRT, but clinically relevant deviations between
      CBCTLUT and rpCT in the spinal cord for IMPT. Gamma-index pass-rates were found
      increased for vCT with respect to CBCTLUT in IMPT (by up to 21 percentage points)
      and IMRT (by up to 9 percentage points) for most cases. The SFUD-based proton
      range assessment showed improved agreement of vCT and rpCT, with 88-99% of the
      depth dose profiles in beam's eye view agreeing within 3 mm. For CBCTLUT, only 80
      94% of the profiles fulfilled this criterion. CONCLUSION: vCT and CBCTLUT are
      suitable options for dose recalculation in adaptive IMRT. In the scope of IMPT,
      the vCT approach is preferable.

PMID- 26198655
TI  - Dose or 'LET' painting--What is optimal in particle therapy of hypoxic tumors?
AB  - BACKGROUND: Dose painting is a concept that may increase the tumor control
      probability (TCP). In particle therapy of hypoxic tumors, it may also be
      beneficial to redistribute the linear energy transfer (LET) so that the oxygen
      effect is minimized; so-called LET painting. The purpose of the present study was
      to use TCP estimates for comparing dose and LET painting of hypoxic tumors.
      MATERIAL AND METHODS: Protons, lithium ions and carbon ions were considered.
      Tumor images tentatively depicting hypoxia were used as input. Optimal dose
      prescription maps were obtained by optimizing TCP under dose and/or LET
      redistribution. TCPs were compared to those resulting from conventional particle
      therapy with no dose or LET painting. The therapeutic gain at a given iso-effect
      was calculated. Treatment adaptation during therapy in response to changes in the
      spatial hypoxia distribution was also considered. RESULTS: Both dose and LET
      painting gave higher TCPs compared to conventional particle therapy, irrespective
      of particle type. The therapeutic gain from LET painting, dose painting and
      combined dose+ LET painting was 1.09/1.43/1.45, 1.24/1.32/1.37 and 1.16/1.23/1.28
      for protons, lithium ions and carbon ions, respectively. The importance of
      treatment adaptation was less pronounced for particles heavier than protons.
      CONCLUSION: Dose painting results in higher TCP than LET painting, in particular
      for protons. For heavier ions, LET painting may also give an enhanced tumor
      effect compared to conventional particle therapy. Combined dose+ LET painting may
      only give a marginally increased effect compared to dose painting only. Adaptive
      carbon ion dose painting seems to be of less importance.

PMID- 26198656
TI  - An image-based method to quantify biomechanical properties of the rectum in
      radiotherapy of prostate cancer.
AB  - BACKGROUND: Gastrointestinal morbidity after radiotherapy (RT) for prostate
      cancer may be related to the biomechanical properties of the rectum. In this
      study we present a magnetic resonance imaging (MRI)-based method to quantitate
      the thickness and elasticity of the rectal wall in prostate cancer patients
      treated with RT. MATERIAL AND METHODS: Four patients previously treated with RT
      for prostate cancer underwent an MRI session with stepwise rectal bag deflation
      (from a maximum tolerable volume to 0 ml, in 50 ml steps), with a probe inserted
      inside the bag to monitor the internal rectal pressure. MRIs were acquired using
      Dixon sequences (4 mm axial slice thickness) at each deflation step. Rectal walls
      were defined from the recto-sigmoid junction to 3 cm above the anal canal as the
      space between the inner and outer wall surfaces. The wall thickness was
      determined and biomechanical properties (strain and stress) were calculated from
      the pressure measurements and the MRI-segmented rectal walls. RESULTS: The
      integral rectal pressure varied for the maximum tolerable volume (range 150-250
      ml) across patients and ranged from 1.3 to 4.0 kPa (SD = 1.2 kPa). Wall thickness
      was found to vary between patients and also across different rectum segments,
      with a mean (SD) thickness for the different segments at the 50 ml distension
      volume of 1.8-4.0 (0.6) mm. Stress showed larger variation than strain, with mean
      (SD) values for the different segments ranging between 1.5 and 7.0 (1.5) kPa.
      CONCLUSION: We have developed a method to quantify biomechanical properties of
      the rectal wall. The resulting rectal wall thickness, strain and stress differed
      between patients, as well as across different rectal wall sections. These
      findings could provide guidance in future predictive outcome modelling in order
      to better understand the rectal dose-volume response relationship.

PMID- 26198657
TI  - New dose constraint reduces radiation-induced fatal pneumonitis in locally
      advanced non-small cell lung cancer patients treated with intensity-modulated
      radiotherapy.
AB  - BACKGROUND: Intensity-modulated radiotherapy (IMRT) in locally advanced non-small
      cell lung cancer (NSCLC) allows treatment of patients with large tumour volumes,
      but radiation pneumonitis (RP) remains a dose limiting complication. The
      incidence of severe RP using three-dimensional (3D) conformal radiotherapy, was
      previously reported to be 17%, with 2% lethal RP. The aim of this study was to
      monitor the incidence of RP following the introduction of IMRT. MATERIAL AND
      METHODS: IMRT was delivered using 4-8 beam arrangements and introduced in three
      phases. In phase I, 12 patients were treated using only one dose constraint
      (V20), in which the total lung volume receiving 20 Gy was limited to 40%. In
      phase II, 25 patients were treated with an additional dose constraint of mean
      lung dose (MLD) <= 20 Gy. In phase III, 50 patients were treated with an extra
      dose constraint (V5) in which the total lung volume receiving a dose of 5 Gy was
      <= 60%. RP was prospectively documented. The results of phase I & II (IMRT-1)
      were compared to those in phase III (IMRT-2). RESULTS: The median follow-up time
      was 17 months. The introduction of IMRT was associated with an increase in the
      incidence of RP in Phase I&II (IMRT-1) to 41%, six of 37 (16%) had grade 5 RP
      (IMRT-1). Introducing the dose constraint V5, led to a significant reduction in
      the lung volume receiving doses <= 20 Gy from 51 +/- 2% to 41 +/- 1% (p <
      0.0001). Introducing V5 constraint did not decrease the incidence of severe
      (grade >= 3) RP, but significantly decreased the lethal pneumonitis to 4% (two of
      50 patients), p = 0.05. CONCLUSION: Introducing IMRT resulted in an increase in
      the incidence of severe and fatal RP, however a new dose constraint to the volume
      of lung receiving low doses reduced the incidence of lethal pneumonitis.

PMID- 26198658
TI  - Evaluation of planning aims and dose prescription in image-guided adaptive
      brachytherapy and radiochemotherapy for cervical cancer: Vienna clinical
      experience in 225 patients from 1998 to 2008.
AB  - BACKGROUND: To assess planning aims (PAs) and dose prescription in image-guided
      adaptive brachytherapy (IGABT) of cervical cancer and investigate potential
      impact on clinical outcome. MATERIAL AND METHODS: Our study population consists
      of 225 consecutive cervical cancer patients (FIGO stages IB-IVA) treated between
      1998 and 2008 at the Medical University of Vienna by external beam radiotherapy
      (EBRT) +/- chemotherapy and IGABT. For this retrospective study, patients were
      stratified into two treatment groups: PA+ group, all dose constraints fulfilled
      for prescription; PA-, one or more dose constraints not fulfilled for
      prescription. The following dose constraints (EBRT+ IGABT) were applied: clinical
      target volume (CTV)HR D90 >= 85 Gy, D2cm3 Rectum < 70 Gy, D2cm3 Bladder < 90 Gy.
      Differences in patient, tumor and treatment characteristics and clinical outcome
      (event: local failure or grade 3 + 4 toxicity) were compared between Group 1 and
      2. Further, the impact of learning period (1998-2000) and protocol period (2001
      2008) on the fulfillment of PAs for dose prescription and clinical outcome was
      analyzed. RESULTS: In the PA+ group there were 77 (34%) and in the PA- group 148
      (66%) patients. In the PA- group, CTVHR D90 < 85 Gy was prescribed in 82
      patients, D2cm3 bladder > 90 Gy was prescribed in 80 patients and D2cm3 Rectum >
      70 Gy in 60 patients. Fulfillment of the PA for dose prescription improved from
      4% in the learning period to 48% in the protocol period. The five-year event-free
      interval was 64% in the learning period and 84% in the protocol period (p =
      0.008). CONCLUSION: Fulfillment of all PAs for dose prescription is challenging -
      especially in patients with more advanced tumors. However, with growing
      experience fulfillment of PA for dose prescription can be significantly increased
      (learning and protocol period). Such increase in fulfilling PA for dose
      prescription is followed by a significant improvement in clinical outcome.

PMID- 26198659
TI  - The evaluation of innovation in radiation oncology--what can we do and what
      should we do?

PMID- 26198661
TI  - Two Patients With Visual Aura - Migraine, Epilepsy, or Migralepsy?
AB  - BACKGROUND: The concept of migralepsy refers to visual migraine auras that
      seemingly evolve into epileptic seizures. It was discussed controversially ever
      since and scientific proof for this entity is scarce. METHODS: We report two
      patients with visual aura fulfilling the diagnostic criteria for migralepsy. In
      both patients, habitual attacks were recorded during long-term video
      electroencephalography (EEG) monitoring. CASE RESULTS: Both patients demonstrated
      unilateral occipital EEG seizure patterns during their long-lasting visual aura,
      which eventually evolved into versive seizures. CONCLUSION: Here, we prove the
      epileptic origin of the visual auras, which have been misdiagnosed as migraine or
      migralepsy before. Additional evaluation should be considered in patients with
      visual aura and hints for an epileptic origin as occipital lobe epilepsy might be
      missed in patients diagnosed with migraine. Based on our patients, we suggest to
      challenge the concept of migralepsy in current classifications.

PMID- 26198662
TI  - Effects of planting Phragmites australis on nitrogen removal, microbial nitrogen
      cycling, and abundance of ammonia-oxidizing and denitrifying microorganisms in
      sediments.
AB  - We examined the effect of planting an emergent aquatic plant (Phragmites
      australis) on nitrogen removal from sediments using a 42-d pot experiment. The
      experimental pot systems comprised two types of sediments planted with and
      without young P. australis. Total nitrogen (total N), total dissolved N, and NH4
      N in the sediments decreased markedly after planting. In contrast, those levels
      decreased only slightly in the unplanted sediments. The decrease in total N in
      the P. australis-planted sediments was 7-20 times those in the unplanted
      sediments. Abundances of bacterial 16S rRNA, archaeal 16S rRNA, ammonia-oxidizing
      bacterial ammonia monooxygenase (amoA), ammonia-oxidizing archaeal amoA, and
      denitrifying bacterial nitrite reductase (nirK) genes increased significantly in
      sediments after planting. Phragmites australis appears to have released oxygen
      and created a repeating cycle of oxidizing and reducing conditions in the
      sediments. These conditions should promote mineralization of organic N,
      nitrification, and denitrification in the sediments. Phragmites australis
      absorbed bioavailable nitrogen generated by microbial nitrogen metabolism. During
      the 42-d period after planting, 31-44% of total N was removed by microbial
      nitrogen cycling, and 56-69% was removed via absorption by P. australis. These
      results suggest that planting P. australis can increase microbial populations and
      their activities, and that nitrogen removal can be accelerated by the combined
      functions of P. australis and microorganisms in the sediment. Thus, planting P.
      australis has considerable potential as an effective remediation technology for
      eutrophic sediments.

PMID- 26198660
TI  - Altered microRNAs expression profiling in cumulus cells from patients with
      polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in
      women of reproductive age, and oocyte developmental competence is altered in
      patients with PCOS. In recent years microRNAs (miRNAs) have emerged as important
      regulators of gene expression, the aim of the study was to study miRNAs
      expression patterns of cumulus cells from PCOS patients. METHODS: The study
      included 20 patients undergoing in vitro fertilization (IVF) and intra
      cytoplasmic sperm injection (ICSI): 10 diagnosed with PCOS and 10 matching
      controls. We used deep sequencing technology to identify the miRNAs
      differentially expressed in the cumulus cells of PCOS. RESULTS: There were 17
      differentially expressed miRNAs in PCOS cumulus cells, including 10 miRNAs
      increase and 7 miRNAs decrease. These miRNAs were predicted to target a large set
      of genes with different functions, including Wnt- and MAPK- signaling pathways,
      oocyte meiosis, progesterone-mediated oocyte maturation and cell cycle.
      Unsupervised hierarchical clustering analysis demonstrated that there was a
      specific miRNAs expression pattern in PCOS cumulus cells. CONCLUSION: We found
      that the miRNAs expression profile was different in cumulus cells isolated from
      PCOS patients compared with control. This study provided new evidence for
      understanding the pathogenesis of PCOS.

PMID- 26198663
TI  - Plasmodium falciparum glucose-6-phosphate dehydrogenase 6-phosphogluconolactonase
      is a potential drug target.
AB  - The malarial parasite Plasmodium falciparum is exposed to substantial redox
      challenges during its complex life cycle. In intraerythrocytic parasites,
      haemoglobin breakdown is a major source of reactive oxygen species. Deficiencies
      in human glucose-6-phosphate dehydrogenase, the initial enzyme in the pentose
      phosphate pathway (PPP), lead to a disturbed redox equilibrium in infected
      erythrocytes and partial protection against severe malaria. In P. falciparum, the
      first two reactions of the PPP are catalysed by the bifunctional enzyme glucose-6
      phosphate dehydrogenase 6-phosphogluconolactonase (PfGluPho). This enzyme differs
      structurally from its human counterparts and represents a potential target for
      drugs. In the present study we used epitope tagging of endogenous PfGluPho to
      verify that the enzyme localises to the parasite cytosol. Furthermore, attempted
      double crossover disruption of the PfGluPho gene indicates that the enzyme is
      essential for the growth of blood stage parasites. As a further step towards
      targeting PfGluPho pharmacologically, ellagic acid was characterised as a potent
      PfGluPho inhibitor with an IC50 of 76 nM. Interestingly, pro-oxidative drugs or
      treatment of the parasites with H2O2 only slightly altered PfGluPho expression or
      activity under the conditions tested. Furthermore, metabolic profiling suggested
      that pro-oxidative drugs do not significantly perturb the abundance of PPP
      intermediates. These data indicate that PfGluPho is essential in asexual
      parasites, but that the oxidative arm of the PPP is not strongly regulated in
      response to oxidative challenge.

PMID- 26198664
TI  - Relationships among symptom severity, coping styles, and quality of life in
      community-dwelling women with urinary incontinence: a multiple mediator model.
AB  - PURPOSE: To investigate the relationships among symptom severity, coping styles,
      and quality of life (QOL) in community-dwelling women with urinary incontinence
      (UI). METHODS: A total of 592 women with UI participated in this cross-sectional
      study. Bivariate Pearson's correlation was used to examine the correlations
      between symptom severity, coping styles, and QOL. Multivariate regression models
      and Sobel tests were used to test the mediating effect of coping styles.
      Additionally, a multiple mediator model was used to examine the mediating role of
      coping styles collectively. All regression models were adjusted for age,
      education, marital status, income, duration of UI, and type of UI. RESULTS:
      Participants tended to use avoidant and palliative coping styles and not use
      instrumental coping style. Avoidant and palliative coping styles were associated
      with poor QOL, and partially mediated the association between symptom severity
      and QOL. Nearly 73% of the adverse effect of symptom severity on QOL was mediated
      by avoidant and palliative coping styles. CONCLUSIONS: The use of avoidant and
      palliative coping styles was higher with more severe urine leakage, and QOL
      tended to be poorer. Coping styles should be addressed in UI management. It may
      be of particular value to look closely at negative coping styles and implement
      education and training of patients in improving their coping skills related to
      managing UI, which will in turn improve their QOL.

PMID- 26198665
TI  - Normative data and psychometric properties of the Connor-Davidson Resilience
      Scale (CD-RISC) and the abbreviated version (CD-RISC2) among the general
      population in Hong Kong.
AB  - PURPOSE: To examine whether the two-item version (CD-RISC2) of the Connor
      Davidson Resilience Scale (CD-RISC) has adequate internal consistency and
      construct validity, as well as significant correlation with the full scale, and
      to provide normative data for the CD-RISC and the CD-RISC2 in a Chinese general
      population in Hong Kong. METHODS: In total, 10,997 randomly selected participants
      aged >=20 years completed the Chinese version of the CD-RISC (including the 2
      items of the CD-RISC2), the Patient Health Questionnaire, Family Harmony Scale,
      Family APGAR, and CAGE Questionnaire. Internal consistency and convergent and
      discriminant validity of the CD-RISC and CD-RISC2 were assessed. RESULTS:
      Cronbach's alpha for CD-RISC and CD-RISC2 was 0.97 and 0.79, respectively. CD
      RISC2 was associated with the 25-item version of the CD-RISC (r = 0.88),
      depressive symptoms (r s = -0.18), family harmony (r = 0.20), family functioning
      (r = 0.27) and was not associated with alcohol consumption (r = 0.05). The mean
      score for the CD-RISC and CD-RISC2 was 59.99 (SD = 13.92) and 5.03 (SD = 1.37),
      respectively. Men, younger individuals, and those with higher education or higher
      household income reported higher resilience levels. CONCLUSIONS: The Chinese
      version of the CD-RISC2 was demonstrated to be a reliable and valid measure in
      assessing resilience among the general population in Hong Kong.

PMID- 26198666
TI  - S-acylation of the Insulin-Responsive Aminopeptidase (IRAP): Quantitative
      analysis and Identification of Modified Cysteines.
AB  - The insulin-responsive aminopeptidase (IRAP) was recently identified as an S
      acylated protein in adipocytes and other tissues. However, there is currently no
      information on the extent of S-acylation of this protein, the residues that are
      modified, or the effects of S-acylation on IRAP localisation. In this study, we
      employ a semi-quantitative acyl-RAC technique to show that approximately 60% of
      IRAP is S-acylated in 3T3-L1 adipocytes. In contrast, S-acylation of GLUT4, a
      glucose transporter that extensively co-localises with IRAP, was approximately
      five-fold lower. Site-directed mutagenesis was employed to map the sites of S
      acylation on IRAP to two cysteine residues, one of which is predicted to lie in
      the cytoplasmic side of the single transmembrane domain and the other which is
      just upstream of this transmembrane domain; our results suggest that these
      cysteines may be modified in a mutually-exclusive manner. Although S-acylation
      regulates the intracellular trafficking of several transmembrane proteins, we did
      not detect any effects of mutating the modified cysteines on the plasma membrane
      localisation of IRAP in HEK293T cells, suggesting that S-acylation is not
      essential for the movement of IRAP through the secretory pathway. 

PMID- 26198667
TI  - Lumbar annulus fibrosus biomechanical characterization in healthy children by
      ultrasound shear wave elastography.
AB  - OBJECTIVES: Intervertebral disc (IVD) is key to spine biomechanics, and it is
      often involved in the cascade leading to spinal deformities such as idiopathic
      scoliosis, especially during the growth spurt. Recent progress in elastography
      techniques allows access to non-invasive measurement of cervical IVD in adults;
      the aim of this study was to determine the feasibility and reliability of shear
      wave elastography in healthy children lumbar IVD. METHODS: Elastography
      measurements were performed in 31 healthy children (6-17 years old), in the
      annulus fibrosus and in the transverse plane of L5-S1 or L4-L5 IVD. Reliability
      was determined by three experienced operators repeating measurements. RESULTS:
      Average shear wave speed in IVD was 2.9 +/- 0.5 m/s; no significant correlations
      were observed with sex, age or body morphology. Intra-operator repeatability was
      5.0 % while inter-operator reproducibility was 6.2 %. Intraclass correlation
      coefficient was higher than 0.9 for each operator. CONCLUSIONS: Feasibility and
      reliability of IVD shear wave elastography were demonstrated. The measurement
      protocol is compatible with clinical routine and the results show the method's
      potential to give an insight into spine deformity progression and early
      detection. KEY POINTS: * Intervertebral disc mechanical properties are key to
      spine biomechanics * Feasibility of shear wave elastography in children lumbar
      disc was assessed * Measurement was fast and reliable * Elastography could
      represent a novel biomarker for spine pathologies.

PMID- 26198669
TI  - Enhancing carrier generation in TiO2 by a synergistic effect between plasmon
      resonance in Ag nanoparticles and optical interference.
AB  - Silver nanoparticles have been embedded at a few nanometer distance from the free
      surface of titania/silica multilayers using low energy ion beam synthesis.
      Transmission electron microscopy shows the presence of 3 nm-sized crystalline
      particles. Reflectance spectroscopy on these composite substrates shows an
      increase of the light capture efficiency in the visible range. This behaviour is
      interpreted as a synergistic effect between plasmon polariton resonance and Fabry
      Perot interferences. Plasmon-resonant Raman spectroscopy is deeply used to
      analyze, on one hand confinement of vibrations and electronic excitations in Ag
      NPs, and on the other hand coupling of polar TiO2 phonons with injected photo
      generated carriers. It is shown how these new Ag/TiO2 nanocomposite films appear
      as very promising to enhance the efficiency and enlarge the spectral sensitivity
      of plasmo-electronics devices. 

PMID- 26198668
TI  - Vacuum-free transparent quantum dot light-emitting diodes with silver nanowire
      cathode.
AB  - Efficient transparent quantum-dot light emitting diodes (QD-LEDs) are
      demonstrated by using a silver nanowire (AgNW) cathode. The devices are
      fabricated through a solution technique, not any vacuum processes are involved.
      Almost identical performance is obtained for both sides of the transparent
      device, which is primary due to the high transmittance of AgNW cathode. The
      maximum luminance (efficiency) for ITO and AgNW side is 25,040 cd/m(2) (5.6 cd/A)
      and 23,440 cd/m(2) (5.2 cd/A), respectively. The average specular transmittance
      of the device (involving the glass substrate) is over 60% in the visible range.
      This study indicates that AgNW electrodes can serve as a cost-effective, flexible
      alternative to ITO, and thereby improve the economic viability and mechanical
      stability of QD-LEDs. All the results suggest that this is an important progress
      toward producing transparent QD-LEDs based displays and lighting sources. 

PMID- 26198670
TI  - Retrospective evaluation of methionine intoxication associated with urinary
      acidifying products in dogs: 1,525 cases (2001-2012).
AB  - OBJECTIVE: To describe the signalment, clinical findings, timing of signs,
      outcome, and prognosis in a population of dogs exposed to methionine through the
      ingestion of urine acidifying products. DESIGN: Retrospective observational study
      from January 1, 2001 to December 31, 2012. SETTING: Animal Poison Control Center.
      ANIMALS: A total of 1,197 case calls yielding 1,525 dogs identified with presumed
      methionine ingestion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Records
      of dogs with presumptive methionine ingestion were reviewed from the American
      Society for the Prevention of Cruelty to Animals Animal Poison Control Center
      database. Ingested methionine doses ranged from 3.9 mg/kg to 23,462 mg/kg.
      Clinical signs developed in 47% of dogs. The most common clinical signs were
      gastrointestinal (GI) and neurologic. The mean onset of GI signs was 2.8 hours
      following ingestion. The mean onset of neurologic signs was 6.8 hours following
      ingestion. GI signs were identified with ingested doses >=22.5 mg/kg. Vomiting
      was the most common GI sign. Neurologic signs were identified with ingested doses
      >=94.6 mg/kg. Ataxia was the most common neurologic sign. Resolution of clinical
      signs occurred within 48 hours of ingestion, and no fatalities were reported.
      CONCLUSIONS: Prognosis for dogs with methionine intoxication is excellent.
      Vomiting and ataxia were the most common clinical signs associated with
      methionine toxicosis.

PMID- 26198672
TI  - Hydrogen spillover on Rh/TiO2: the FTIR study of donated electrons, co-adsorbed
      CO and H/D exchange.
AB  - Hydrogen dissociation and spillover on supported metal nanoparticles have
      received renewed interest because these chemical processes are closely related to
      applications in heterogeneous catalysis and hydrogen storage. In heterogeneous
      catalysis, spillover can control the reaction rate and selectivity of a wide
      range of reactions, e.g. hydrogenation, synthesis of methanol and
      hydroisomerization. In this work, we combine three spectroscopic approaches, i.e.
      the FT-IR spectroscopy of donated electrons, co-adsorbed CO and H/D exchange, to
      obtain detailed information on the dynamics of hydrogen interaction with a model
      1.3% Rh/TiO2 catalyst. Our spectroscopic results helped us to build a physical
      picture of the processes occurring during the H-spillover on Rh/TiO2. It was
      found that molecular H2 dissociates on nanocrystalline Rh; H atoms spillover onto
      the titania thus protonating the semiconductor, while donating electrons to
      shallow trap (ST) states and the conduction band (CB) of TiO2. These donated
      electrons are observed by their specific IR features. By simultaneously
      monitoring the changes in the vibrational modes of CO, and, the infrared
      absorbance due to transitions involving CB and ST electrons, we found that both
      CO-reduced and partially re-oxidized Rh nanocrystallites promote the H-spillover
      and thus the n-doping of TiO2 materials. Upon evacuation, the process reverses:
      hydrogen atoms spillover back to Rh nanoparticles where they recombine to form H2
      molecules that desorb from the surface. These new mechanistic insights into the
      process of H2 dissociation and spillover on the powder Rh/TiO2 catalyst call for
      further model surface science studies with model metal nanoparticle-single
      crystal substrate systems, in which a detailed picture of energetics and spatial
      distribution of hydrogen and injected electrons could be obtained. 

PMID- 26198671
TI  - Functional Loss of Bmsei Causes Thermosensitive Epilepsy in Contractile Mutant
      Silkworm, Bombyx mori.
AB  - The thermoprotective mechanisms of insects remain largely unknown. We reported
      the Bombyx mori contractile (cot) behavioral mutant with thermo-sensitive
      seizures phenotype. At elevated temperatures, the cot mutant exhibit seizures
      associated with strong contractions, rolling, vomiting, and a temporary lack of
      movement. We narrowed a region containing cot to ~268 kb by positional cloning
      and identified the mutant gene as Bmsei which encoded a potassium channel
      protein. Bmsei was present in both the cell membrane and cytoplasm in wild-type
      ganglia but faint in cot. Furthermore, Bmsei was markedly decreased upon high
      temperature treatment in cot mutant. With the RNAi method and injecting potassium
      channel blockers, the wild type silkworm was induced the cot phenotype. These
      results demonstrated that Bmsei was responsible for the cot mutant phenotype and
      played an important role in thermoprotection in silkworm. Meanwhile, comparative
      proteomic approach was used to investigate the proteomic differences. The results
      showed that the protein of Hsp-1 and Tn1 were significantly decreased and
      increased on protein level in cot mutant after thermo-stimulus, respectively. Our
      data provide insights into the mechanism of thermoprotection in insect. As cot
      phenotype closely resembles human epilepsy, cot might be a potential model for
      the mechanism of epilepsy in future. 

PMID- 26198673
TI  - Association of matrix metalloproteinase family gene polymorphisms with lung
      cancer risk: logistic regression and generalized odds of published data.
AB  - Many studies have reported the association between the matrix metalloproteinase
      (MMP) polymorphisms and lung cancer susceptibility, but the results were
      inconclusive. We conducted a meta-analysis, using a comprehensive strategy based
      on the logistic regression and a model-free approach, to derive a more precise
      estimation of the relationship between MMP1, MMP2, MMP9 and MMP13 polymorphisms
      with lung cancer risk. A total of 22 case-control studies including 8202 cases
      and 7578 controls were included in this meta-analysis. For MMP1-1607 1G/2G,
      increased lung cancer risk was found among Asians in additive model(OR = 1.34,
      95%CI:1.18-1.53) and with model-free approach(ORG = 1.41, 95%CI:1.21-1.65). For
      MMP2-1306 C/T and -735 C/T, based on the model-free approach, a significantly
      reduced risk was found in Asians(MMP2-1306 C/T:ORG = 0.49,95%CI:0.42-0.57; MMP2
      735 C/T: ORG = 0.71, 95%CI:0.61-0.84). For MMP9-1562 C/T, a significantly
      increased risk was found among Asians(OR = 2.73, 95%CI:1.74-4.27) with model-free
      approach. For MMP13-77A/G, there was no association between this polymorphism and
      lung cancer risk in the recessive model(OR = 1.02, 95%CI:0.83-1.26) and with the
      model-free approach(ORG = 0.95, 95%CI:0.76-1.17). Therefore, this meta-analysis
      suggests that the MMP1-1607 1G/2G, MMP2-1306 C/T, MMP2-735 C/T, MMP9 -1562 C/T
      polymorphisms were risk factors for lung cancer among Asians, while MMP13 -77A/G
      polymorphism was not associated with lung cancer risk.

PMID- 26198674
TI  - Renal outcomes analysis after endovascular and open aortic aneurysm repair.
AB  - OBJECTIVE: The purpose of this study was to compare renal outcomes (glomerular
      filtration rate [GFR] and renal volume) after endovascular aneurysm repair (EVAR)
      and open repair (OR) of abdominal aortic aneurysm (AAA). METHODS: All AAA repairs
      performed between November 2009 and July 2011 were included in this retrospective
      study. Patients requiring suprarenal clamping and renal bypass or reimplantation
      and patients requiring fenestrated endografting were excluded from the OR and
      EVAR groups, respectively. All EVARs were performed with transrenal proximal
      fixation. Renal volume (calculated with a three-dimensional workstation) and GFR
      (estimated with the Modification of Diet in Renal Disease formula) were evaluated
      before the procedure, at 12 months after the procedure, and yearly thereafter.
      RESULTS: The study included 90 patients (41 ORs and 49 EVARs). Both groups were
      comparable except for age at intervention, body mass index, smoking, peripheral
      arterial disease, arrhythmia, and vitamin K antagonist treatment. Median follow
      up was 2.8 years for OR (2.5-2.9 years) and 3.2 years for EVAR (3.0-3.4 years).
      In both groups, we found a significant decrease when comparing postoperative
      estimated GFR with 1-year (14.4% decrease [3.8%-23.8%]; P = .002) and 3-year
      (12.8% decrease [3.8%-20.9%]; P = .0007) levels. In both groups, total renal
      volumes significantly diminished. Median preoperative total renal volume (372
      cm(3) [311-349]) significantly decreased (6.7% [2.8%-10.5%]; P = .008) between 1
      year and 2 years of follow-up. CONCLUSIONS: Renal function impairment is similar
      after open and endovascular AAA repair. It is associated with a decrease in total
      renal volume, which seems to be an early and constant marker of postoperative
      renal impairment.

PMID- 26198675
TI  - Does a decision aid improve informed choice in mammography screening? Study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: When invited for the first time at age 50, most women in Germany have
      to decide whether they wish to participate in the German mammography screening
      programme. For ethical reasons, screening decisions should be informed choices,
      but this is rarely the case with mammography screening. Decision aids are
      interventions with the potential to support informed choice by improving the
      following factors: knowledge, clarity of personal attitude, and implementation of
      an intention. Currently, no systematically evaluated decision aid exists for the
      German mammography screening programme. Therefore, the objective of this
      randomized controlled trial is to assess the effectiveness of a decision aid for
      first-time mammography screening programme invitees. METHODS/DESIGN: We have
      developed a decision aid for women invited to the mammography screening programme
      for the first time based on the criteria of the International Patient Decision
      Aids Standards Collaboration. The effectiveness of the decision aid will be
      evaluated in a randomized controlled trial with a 3-month follow-up. We will
      invite 7400 women aged 50 years from the district of Westfalen-Lippe, Germany, to
      participate. This sample will be drawn from registration office data. The primary
      outcome will be informed choice. The secondary outcomes will be the components of
      informed choice (knowledge, attitude, decision/implementation). Decisional
      conflict, decision regret, eHealth literacy, health behaviours, perceived
      behavioural control, subjective norms, invitation status, and demographic
      variables will be assessed. Data will be collected online at baseline, post
      intervention, and at the 3-month follow-up. Participants will be randomized to
      receive either the decision aid or usual care (invitation and standard leaflet of
      the mammography screening programme). DISCUSSION: This paper describes the
      evaluation of a decision aid for the German mammography screening programme in a
      randomized controlled trial. If the decision aid proves to be an effective tool
      to enhance the rate of informed choice, it will be made accessible to the public
      and the use of this decision aid for first-time invitees will be recommended. The
      long-term effect could be an improvement in informed choices in women invited to
      the mammography screening programme. TRIAL REGISTRATION: German Clinical Trials
      Register DRKS00005176.

PMID- 26198678
TI  - Case 3: a toddler with orbital swelling.
AB  - The radiologic work-up of a child with an aggressive lesion of the bony orbit is
      discussed through the details of a specific case. 

PMID- 26198677
TI  - Imaging of systemic vasculitis in childhood.
AB  - The term "systemic vasculitis" encompasses a diverse set of diseases linked by
      the presence of blood-vessel inflammation that are often associated with critical
      complications. These diseases are uncommon in childhood and are frequently
      subjected to a delayed diagnosis. Although the diagnosis and treatment may be
      similar for adult and childhood systemic vasculitides, the prevalence and
      classification vary according to the age group under investigation. For example,
      Kawasaki disease affects children while it is rarely encountered in adults. In
      2006, the European League Against Rheumatism (EULAR) and the Pediatric
      Rheumatology European Society (PReS) proposed a classification system for
      childhood vasculitis adopting the system devised in the Chapel Hill Consensus
      Conference in 1993, which categorizes vasculitides according to the predominant
      size of the involved blood vessels into small, medium and large vessel diseases.
      Currently, medical imaging has a pivotal role in the diagnosis of vasculitis
      given recent developments in the imaging of blood vessels. For example, early
      diagnosis of coronary artery aneurysms, a serious complication of Kawasaki
      disease, is now possible by magnetic resonance imaging (MRI) of the heart and
      multidetector computed tomography (MDCT); positron emission tomography/CT
      (PET/CT) helps to assess active vascular inflammation in Takayasu arteritis. Our
      review offers a unique approach using the integration of the proposed
      classification criteria for common systemic childhood vasculitides with their
      most frequent imaging findings, along with differential diagnoses and an
      algorithm for diagnosis based on common findings. It should help radiologists and
      clinicians reach an early diagnosis, therefore facilitating the ultimate goal of
      proper management of affected children. 

PMID- 26198681
TI  - The feather louse genus Mulcticola Clay et Meinertzhagen, 1938 (Phthiraptera:
      Philopteridae) from Brazil, with descriptions of five new species and catalogue
      for species described in the genus.
AB  - Five new species of Mulcticola Clay et Meinertzhagen, 1938 are described and
      illustrated from Brazil. These new species and their hosts are: Mulcticola sicki
      sp. n. from the sand-coloured nighthawk, Chordeiles rupestris rupestris (Spix),
      Mulcticola bacurau sp. n. from the common pauraque, Nyctidromus albicollis
      (Gmelin), Mulcticola tendeiroi sp. n. from the long-trained nightjar, Macropsalis
      forcipata (Nitzsch), Mulcticola piacentinii sp. n. from the short-tailed
      nighthawk, Lurocalis semitorquatus semitorquatus (Gmelin) (type-host) and L. s.
      nattereri (Temminck), and Mulcticola parvulus sp. n. from the little nightjar,
      Setopagis parvula (Gould). These species were compared primarily with Mulcticola
      nacunda Carriker, 1945 from the nacunda nighthawk, Chordeiles nacunda nacunda
      (Vieillot), which is one of the species of Mulcticola previously recorded in the
      Neotropical region. All the five new species described herein differ from their
      congeners by exclusive characters such as the shape of anterior dorsal head
      plate, metasternal plate, subvulvar plates in females and genitalia in males. We
      increased the number of species in Mulcticola to 18 in total, with seven of them
      now known from the Neotropics. We present the main morphological characters to
      distinguish Mulcticola from other species of the Philopteridae parasitising
      Caprimulgiformes and also compile a detailed catalogue for species included in
      this louse genus. 

PMID- 26198683
TI  - A passive flow regulator with low threshold pressure for high-throughput inertial
      isolation of microbeads.
AB  - In this work, we present a novel passive flow regulator fabricated by stacking
      five functional layers. To understand the flow-rate regulation characteristics, a
      series of prototype devices with different structural dimensions are
      investigated. The experimental results show that our regulator can exhibit a
      constant delivery flow rate of up to 4.38 +/- 0.1 ml min(-1) with variations less
      than 5%, and the minimum threshold pressure for achieving a constant flow rate is
      only 10 kPa. As compared with previously reported regulators, our regulator
      offers a much wider flow-rate regulation range under lower threshold pressures.
      To validate the practical function of our regulator, a low pressure gas-driven
      flow system integrated with two passive flow regulators and a Dean flow
      fractionation chip is constructed to achieve high-throughput inertial isolation
      of differently sized microbeads. The isolation performance is found to be totally
      independent of the inlet pressure, which permits the use of portable and low-cost
      flow-driving apparatus for accurate flow control. Therefore, the passive flow
      regulator proposed in our work is potentially useful for the steady injection and
      accurate control of the sample fluid in low cost, miniaturized microfluidic
      systems. 

PMID- 26198682
TI  - Exercise-Induced Repolarization Changes in Patients with Isolated Myocardial
      Bridging.
AB  - BACKGROUND: Although myocardial bridging (MB) is defined as an angiographic
      phenomenon with a benign course, it has also been associated with adverse
      cardiovascular events. The effects of exercise on myocardial repolarization in
      patients with MB were tested in this study, with Tp-e and Tp-e/QT repolarization
      indexes. MATERIAL AND METHODS: A total of 50 patients in whom isolated MB was
      diagnosed at coronary angiography (CAG) (Group I) and 48 patients with normal CAG
      results (Group II) were included in this study. The participants underwent
      treadmill exercise stress testing according to the Bruce protocol. QT dispersion
      (QTd) was defined as the minimum QT interval subtracted from the maximum. The Tp
      e interval was defined as the difference between the QT and the QT peak time
      period. QTd and Tp-e intervals were calculated for all patients before and after
      exercise testing and differences between groups were compared. RESULTS: At peak
      exercise, QTd and cQTd showed a significant increase in comparison to baseline
      values in the group of patients with myocardial bridges. Significant increases
      were also found with exercise in the Tp-e, cTp-e durations and Tp-e/QT ratio of
      the MB patient group in comparison to the baseline values. On the other hand,
      significant differences in QTd, cQTd, Tp-e, cTp-e intervals, and Tp-e/QT ratio
      during peak exercise in comparison with baseline values were not detected in the
      control group (p>0.05). CONCLUSIONS: Significant increases in QTd, cQTd, Tp-e and
      cTp-e intervals and Tp-e/QT ratio were detected in the MB patients during
      exercise testing.

PMID- 26198684
TI  - Shoulder arthroplasty in patients with Parkinson's disease is associated with
      increased complications.
AB  - BACKGROUND: Case series suggest a higher postoperative complication rate after
      shoulder arthroplasty in patients with Parkinson's disease (PD). The purpose of
      this study was to evaluate the perioperative complications in patients with PD
      undergoing conventional total shoulder arthroplasty (TSA), reverse shoulder
      arthroplasty (RSA), and shoulder hemiarthroplasty (HA). METHODS: Patients with PD
      who underwent TSA, RSA, or HA were identified in a national insurance database
      and then matched to controls without a diagnosis of PD based on age, gender,
      obesity, diabetes, and tobacco use. Complications were assessed, including
      infection, dislocation, revision, stiffness, fracture, component loosening, and
      systemic complications. RESULTS: The final study cohorts included 3390 TSA
      patients with PD and 47,034 matched TSA controls; 809 RSA patients with PD and
      14,262 matched controls; and 2833 HA patients with PD and 38,850 matched
      controls. PD was associated with significant higher rates of infection (odds
      ratio [OR], 1.5, 1.7, 1.5, respectively), dislocation (OR, 2.5, 2.0, 2.8,
      respectively), revision arthroplasty (OR, 1.7, 1.8, 1.4, respectively), and
      systemic complications (OR, 1.4, 1.7, 1.3, respectively) after all 3 types of
      shoulder arthroplasty and with higher rates of periprosthetic fracture after
      conventional TSA (OR, 1.5) and shoulder HA (OR, 1.5). Component loosening was
      also more commonly noted in patients with PD after conventional TSA (OR, 1.5) and
      HA (OR, 1.9). CONCLUSION: PD is associated with increased rates of infection,
      dislocation, revision shoulder arthroplasty, fracture, component loosening, and
      systemic complications after conventional TSA, RSA, and shoulder HA.

PMID- 26198685
TI  - Influence of urban neighbourhood environment on physical activity and obesity
      related diseases.
AB  - OBJECTIVES: The impact of characteristics of neighbourhood environment on
      physical activity and obesity-related diseases is still the subject of debate.
      This study aimed to explore the impact of urban neighbourhood environment on
      physical activity and obesity-related diseases. STUDY DESIGN: Cross-sectional
      study. METHODS: Individuals who participated in the 2009 national health
      screening programme, submitted all necessary information, and had lived in
      Community 1 (Haengdang) or Community 2 (Ilsan) for at least 2 years (n = 16,178)
      were selected for inclusion in this study. Anthropometric measures were taken and
      physical activity was assessed using a short questionnaire. RESULTS: No
      significant difference in the trigger factors for walking, including the amount
      of neighbourhood park space, number of shopping malls, and distance between the
      community and shopping malls, was found between the two communities. However,
      Community 2 had a better street environment than Community 1. Participants who
      lived in Community 2 were more physically active [adjusted odds ratio (OR) 1.31,
      95% confidence interval (CI) 1.16-1.48] and walked more regularly (adjusted OR
      1.09, 95% CI 1.02-1.17) than participants who lived in Community 1, and were less
      likely to have abdominal obesity (adjusted OR 0.83, 95% CI 0.77-0.91),
      hypertension (adjusted OR 0.88, 95% CI 0.80-0.97) and diabetes (adjusted OR 0.86,
      95% CI 0.75-0.99). However, the risk of dyslipidaemia, especially in terms of low
      density lipoprotein cholesterol, was higher in Community 2. CONCLUSIONS: These
      results suggest that a walkable environment has a positive influence on
      hypertension and diabetes, and physical activity is the possible mechanism for
      this association. A walkable environment may function as an important tool for
      health promotion in urban areas.

PMID- 26198686
TI  - Laterality judgments in people with low back pain--A cross-sectional
      observational and test-retest reliability study.
AB  - BACKGROUND: Disruption of cortical representation, or body schema, has been
      indicated as a factor in the persistence and recurrence of low back pain (LBP).
      This has been observed through impaired laterality judgment ability and it has
      been suggested that this ability is affected in a spatial rather than anatomical
      manner. OBJECTIVES: We compared laterality judgment performance of foot and trunk
      movements between people with LBP with or without leg pain and healthy controls,
      and investigated associations between test performance and pain. We also assessed
      the test-retest reliability of the Recognise OnlineTM software when used in a
      clinical and a home setting. DESIGN: Cross-sectional observational and test
      retest study. METHODS: Thirty individuals with LBP and 30 healthy controls
      performed judgment tests of foot and trunk laterality once supervised in a clinic
      and twice at home. RESULTS: No statistically significant group differences were
      found. LBP intensity was negatively related to trunk laterality accuracy (p =
      0.019). Intraclass correlation values ranged from 0.51 to 0.91. Reaction time
      improved significantly between test occasions while accuracy did not.
      CONCLUSIONS: Laterality judgments were not impaired in subjects with LBP compared
      to controls. Further research may clarify the relationship between pain
      mechanisms in LBP and laterality judgment ability. Reliability values were mostly
      acceptable, with wide and low confidence intervals, suggesting test-retest
      reliability for Recognise OnlineTM could be questioned in this trial. A
      significant learning effect was observed which should be considered in clinical
      and research application of the test.

PMID- 26198687
TI  - Notes on the history of the Dr. Senckenbergische Anatomie in Frankfurt/Main. Part
      II. The Dr. Senckenbergische Anatomie during the Third Reich and its body supply.
AB  - In order to be able to understand how body supply was maintained at the Dr.
      Senckenbergische Anatomie from 1933 to 1945 - with special emphasis on victims of
      the National Socialist regime - we have collected information from various and
      often fragmentary sources. The documents reveal that during this period at least
      474 bodies were brought to the anatomical institute. Among them were the bodies
      of at least 71 prisoners, 51 of whom had been executed, and the bodies of 8
      inmates of (labor-) camps. 356 unclaimed bodies were received, some of them may
      stem from victims of "euthanasia" programs. The sources of 39, as of yet, unnamed
      bodies could not be verified. The current collections and the catalogs were
      screened for remains of victims of the National Socialist regime, but none were
      found. The vast majority of the bodies were used for teaching purposes. Hans
      Schreiber, one of the directors of the institute, whose biography is provided
      here, used at least 9 additional executed individuals for his research. Wherever
      possible, we have identified the victims of the National Socialist regime,
      executed persons and the inmates of (labor-) camps, whose bodies were used by the
      anatomists in Frankfurt, by name. Among the victims was Georg Froba, a communist
      philanthropist, whose biography is provided. 

PMID- 26198689
TI  - Comorbidity of intellectual disability confounds ascertainment of autism:
      implications for genetic diagnosis.
AB  - While recent studies suggest a converging role for genetic factors towards risk
      for nosologically distinct disorders including autism, intellectual disability
      (ID), and epilepsy, current estimates of autism prevalence fail to take into
      account the impact of comorbidity of these disorders on autism diagnosis. We
      aimed to assess the effect of comorbidity on the diagnosis and prevalence of
      autism by analyzing 11 years (2000-2010) of special education enrollment data on
      approximately 6.2 million children per year. We found a 331% increase in the
      prevalence of autism from 2000 to 2010 within special education, potentially due
      to a diagnostic recategorization from frequently comorbid features such as ID.
      The decrease in ID prevalence equaled an average of 64.2% of the increase of
      autism prevalence for children aged 3-18 years. The proportion of ID cases
      potentially undergoing recategorization to autism was higher (P = 0.007) among
      older children (75%) than younger children (48%). Some US states showed
      significant negative correlations between the prevalence of autism compared to
      that of ID while others did not, suggesting state-specific health policy to be a
      major factor in categorizing autism. Further, a high frequency of autistic
      features was observed when individuals with classically defined genetic syndromes
      were evaluated for autism using standardized instruments. Our results suggest
      that current ascertainment practices are based on a single facet of autism
      specific clinical features and do not consider associated comorbidities that may
      confound diagnosis. Longitudinal studies with detailed phenotyping and deep
      molecular genetic analyses are necessary to completely understand the cause of
      this complex disorder.

PMID- 26198690
TI  - Which adults in the Paris metropolitan area have never been tested for HIV? A
      2010 multilevel, cross-sectional, population-based study.
AB  - BACKGROUND: Despite the widespread offer of free HIV testing in France, the
      proportion of people who have never been tested remains high. The objective of
      this study was to identify, in men and women separately, the various factors
      independently associated with no lifetime HIV testing. METHODS: We used
      multilevel logistic regression models on data from the SIRS cohort, which
      included 3006 French-speaking adults as a representative sample of the adult
      population in the Paris metropolitan area in 2010. The lifetime absence of any
      HIV testing was studied in relation to individual demographic and socioeconomic
      factors, psychosocial characteristics, sexual biographies, HIV prevention
      behaviors, attitudes towards people living with HIV/AIDS (PLWHA), and certain
      neighborhood characteristics. RESULTS: In 2010, in the Paris area, men were less
      likely to have been tested for HIV at least once during their lifetime than
      women. In multivariate analysis, in both sexes, never having been tested was
      significantly associated with an age younger or older than the middle-age group
      (30-44 years), a low education level, a low self-perception of HIV risk, not
      knowing any PLWHA, a low lifetime number of couple relationships, and the absence
      of any history of STIs. In women, other associated factors were not having a
      child < 20 years of age, not having additional health insurance, having had no or
      only one sexual partner in the previous 5 years, living in a cohabiting couple or
      having no relationship at the time of the survey, and a feeling of belonging to a
      community. Men with specific health insurance for low-income individuals were
      less likely to have never been tested, and those with a high stigma score towards
      PLWHA were more likely to be never-testers. Our study also found neighborhood
      differences in the likelihood of men never having been tested, which was, at
      least partially, explained by the neighborhood proportion of immigrants. In
      contrast, in women, no contextual variable was significantly associated with
      never-testing for HIV after adjustment for individual characteristics.
      CONCLUSIONS: Studies such as this one can help target people who have never been
      tested in the context of recommendations for universal HIV screening in primary
      care.

PMID- 26198691
TI  - Effects of landmark distance and stability on accuracy of reward relocation.
AB  - Although small-scale navigation is well studied in a wide range of species, much
      of what is known about landmark use by vertebrates is based on laboratory
      experiments. To investigate how vertebrates in the wild use landmarks, we trained
      wild male rufous hummingbirds to feed from a flower that was placed in a constant
      spatial relationship with two artificial landmarks. In the first experiment, the
      landmarks and flower were 0.25, 0.5 or 1 m apart and we always moved them 3-4 m
      after each visit by the bird. In the second experiment, the landmarks and flower
      were always 0.25 m apart and we moved them either 1 or 0.25 m between trials. In
      tests, in which we removed the flower, the hummingbirds stopped closer to the
      predicted flower location when the landmarks had been closer to the flower during
      training. However, while the distance that the birds stopped from the landmarks
      and predicted flower location was unaffected by the distance that the landmarks
      moved between trials, the birds directed their search nearer to the predicted
      direction of the flower, relative to the landmarks, when the landmarks and flower
      were more stable in the environment. In the field, then, landmarks alone were
      sufficient for the birds to determine the distance of a reward but not its
      direction. 

PMID- 26198692
TI  - Runs of homozygosity and distribution of functional variants in the cattle
      genome.
AB  - BACKGROUND: Recent developments in sequencing technology have facilitated
      widespread investigations of genomic variants, including continuous stretches of
      homozygous genomic regions. For cattle, a large proportion of these runs of
      homozygosity (ROH) are likely the result of inbreeding due to the accumulation of
      elite alleles from long-term selective breeding programs. In the present study,
      ROH were characterized in four cattle breeds with whole genome sequence data and
      the distribution of predicted functional variants was detected in ROH regions and
      across different ROH length classes. RESULTS: On average, 19.5% of the genome was
      located in ROH across four cattle breeds. There were an average of 715.5 ROH per
      genome with an average size of ~750 kbp, ranging from 10 (minimum size
      considered) to 49,290 kbp. There was a significant correlation between shared
      short ROH regions and regions putatively under selection (p < 0.001). By
      investigating the relationship between ROH and the predicted deleterious and non
      deleterious variants, we gained insight into the distribution of functional
      variation in inbred (ROH) regions. Predicted deleterious variants were more
      enriched in ROH regions than predicted non-deleterious variants, which is
      consistent with observations in the human genome. We also found that increased
      enrichment of deleterious variants was significantly higher in short (<100 kbp)
      and medium (0.1 to 3 Mbp) ROH regions compared with long (>3 Mbp) ROH regions (P
      < 0.001), which is different than what has been observed in the human genome.
      CONCLUSIONS: This study illustrates the distribution of ROH and functional
      variants within ROH in cattle populations. These patterns are different from
      those in the human genome but consistent with the natural history of cattle
      populations, which is confirmed by the significant correlation between shared
      short ROH regions and regions putatively under selection. These findings
      contribute to understanding the effects of inbreeding and probably selection in
      shaping the distribution of functional variants in the cattle genome.

PMID- 26198694
TI  - Secondary aneurysmal bone cyst in the distal humerus after resection of intra
      articular nodular fasciitis of the elbow.
AB  - BACKGROUND: Nodular fasciitis most often occurs within subcutaneous tissues, but
      may also arise within skeletal muscle, dermis, vessels, peripheral nerves and,
      although rarely, within joints. Knowledge regarding the cause of aneurysmal bone
      cysts, its natural history, and the results of treatment is limited. Secondary
      aneurysmal bone cysts are associated with other neoplastic processes. Intra
      articular nodular fasciitis in the elbow joint has not been reported previously,
      nor has the development of aneurysmal bone cyst secondary to intra-articular
      nodular fasciitis in the elbow joint. CASE PRESENTATION: We report an unusual
      case of a Japanese 13-year-old boy who presented with a 1-year history of right
      elbow pain. The onset of pain was insidious, without antecedent trauma. On
      physical examination, the range of motion of the elbow was limited. Grip strength
      was reduced in the affected extremity. Incisional biopsy was performed and
      histologic findings revealed nodular fasciitis in the elbow joint. After tumor
      excision, a secondary aneurysmal bone cyst in the distal humerus developed.
      Endoscopy-assisted curettage and artificial bone grafting were performed. One
      year after surgery, a plain radiography showed no recurrence, and the patient
      returned to his daily activities without any symptoms. CONCLUSION: An aneurysmal
      bone cyst in the distal humerus developed after excision of intra-articular
      nodular fasciitis arising in the elbow. The secondary aneurysmal bone cyst
      successfully healed after endoscopy-assisted curettage and artificial bone
      grafting. The findings of this case suggest that these two tumors reside in the
      same biologic spectrum defined as USP6-induced tumors.

PMID- 26198693
TI  - Dual Receptor-Targeted Theranostic Nanoparticles for Localized Delivery and
      Activation of Photodynamic Therapy Drug in Glioblastomas.
AB  - Targeting gold nanoparticles (AuNPs) with two or more receptor binding peptides
      has been proposed to address intratumoral heterogeneity of glioblastomas that
      overexpress multiple cell surface receptors to ultimately improve therapeutic
      efficacy. AuNPs conjugated with peptides against both the epidermal growth factor
      and transferrin receptors and loaded with the photosensitizer phthalocyanine 4
      (Pc 4) have been designed and compared with monotargeted AuNPs for in vitro and
      in vivo studies. The (EGFpep+Tfpep)-AuNPs-Pc 4 with a particle size of ~41 nm
      improved both specificity and worked synergistically to decrease time of maximal
      accumulation in human glioma cells that overexpressed two cell surface receptors
      as compared to cells that overexpressed only one. Enhanced cellular association
      and increased cytotoxicity were achieved. In vivo studies show notable
      accumulation of these agents in the brain tumor regions. 

PMID- 26198695
TI  - Patterns of EPIYA motifs among cagA-positive Helicobacter pylori strains: a case
      control study in a Turkish population with Eurasian geographical features.
AB  - Geographical variation in the frequency of various gastroduodenal pathologies was
      shown to be related to the geographical diversity of H. pylori CagA Glu-Pro-Ile
      Tyr-Ala (EPIYA) patterns. We examined the EPIYA patterns of H. pylori and the
      association of EPIYA patterns with gastric cancer (GC) for the first time, to the
      best of our knowledge, in Turkey. The patient group (PG) contained 60 patients
      [38 GC and 22 duodenal ulcer (DU) patients]. The control group (CG) was 110
      individuals [94 gastritis patients and 16 persons with a normal gastrointestinal
      system (NGIS)]. Specific primers were used for the detection of cagA including
      empty-site-positive and EPIYA-A, -B, -C, -D PCR. Bands of EPIYA-A, -B, -C were
      confirmed by DNA sequencing. One hundred and forty-two (83.5 %) strains [60 in
      the PG (38 GC, 22 DU), 82 in the CG (72 gastritis, 10 NGIS)] were positive for
      the cagA gene. EPIYA-C with multiple repeats was detected in 34 (23.9 %) strains,
      and 22 (64.7 %) were from GC patients. EPIYA-C with one repeat was detected in 89
      (62.7 %) strains, and 54 (60.7 %) were from gastritis patients. EPIYT was
      detected in 10 strains, and EPIYA-D was not detected. The number of EPIYA-C with
      multiple repeats was significantly higher for the PG than for the CG (P <
      0.0001). In GC patients, the number of EPIYA-C with multiple repeats was
      significantly higher than one repeat (P < 0.0001). In conclusion, our study
      showed that multiple EPIYA-C repeats increases the GC risk by 30.6-fold and the
      DU risk by 8.9-fold versus the CG. This indicates that Western-type H. pylori
      strains in Turkey have similar EPIYA motifs to those of neighbouring countries
      and Western populations.

PMID- 26198696
TI  - Extracting antipsychotic polypharmacy data from electronic health records:
      developing and evaluating a novel process.
AB  - BACKGROUND: Antipsychotic prescription information is commonly derived from
      structured fields in clinical health records. However, utilising diverse and
      comprehensive sources of information is especially important when investigating
      less frequent patterns of medication prescribing such as antipsychotic
      polypharmacy (APP). This study describes and evaluates a novel method of
      extracting APP data from both structured and free-text fields in electronic
      health records (EHRs), and its use for research purposes. METHODS: Using
      anonymised EHRs, we identified a cohort of patients with serious mental illness
      (SMI) who were treated in South London and Maudsley NHS Foundation Trust mental
      health care services between 1 January and 30 June 2012. Information about
      antipsychotic co-prescribing was extracted using a combination of natural
      language processing and a bespoke algorithm. The validity of the data derived
      through this process was assessed against a manually coded gold standard to
      establish precision and recall. Lastly, we estimated the prevalence and patterns
      of antipsychotic polypharmacy. RESULTS: Individual instances of antipsychotic
      prescribing were detected with high precision (0.94 to 0.97) and moderate recall
      (0.57-0.77). We detected baseline APP (two or more antipsychotics prescribed in
      any 6-week window) with 0.92 precision and 0.74 recall and long-term APP
      (antipsychotic co-prescribing for 6 months) with 0.94 precision and 0.60 recall.
      Of the 7,201 SMI patients receiving active care during the observation period,
      338 (4.7 %; 95 % CI 4.2-5.2) were identified as receiving long-term APP. Two
      second generation antipsychotics (64.8 %); and first -second generation
      antipsychotics were most commonly co-prescribed (32.5 %). CONCLUSIONS: These
      results suggest that this is a potentially practical tool for identifying
      polypharmacy from mental health EHRs on a large scale. Furthermore, extracted
      data can be used to allow researchers to characterize patterns of polypharmacy
      over time including different drug combinations, trends in polypharmacy
      prescribing, predictors of polypharmacy prescribing and the impact of
      polypharmacy on patient outcomes.

PMID- 26198697
TI  - Intraoperative detection of sentinel lymph node metastases in breast carcinoma by
      Fourier transform infrared spectroscopy.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy is a routine surgical staging
      procedure in clinically lymph node-negative breast cancer. Fourier transform
      infrared (FTIR) spectroscopy, a technique based on the biochemical composition of
      the tissue, has previously been found to be capable of differentiating between
      normal and malignant tissue. The aim of the present study was to explore the
      intraoperative use of FTIR spectroscopy for rapidly identifying metastatic SLNs,
      and distinguishing between metastatic and non-metastatic tissue. METHODS: Freshly
      removed SLNs from patients with breast cancer were analysed. Samples were
      measured by FTIR spectroscopy before histopathological diagnosis. The FTIR
      spectrum of each sample identified ten bands from 2000 to 900 cm(-1) . The peak
      position, intensity and full width at half maximum of each absorbent band were
      measured, and the relative intensity ratios calculated. Canonical discriminant
      analysis was performed to discriminate between metastatic and non-metastatic
      samples. RESULTS: A total of 149 SLNs were removed from 49 patients.
      Histopathological examination confirmed 38 metastatic and 111 non-metastatic
      SLNs. Eighteen of 29 parameters were significantly different between the
      metastatic and non-metastatic SLNs. Five parameters were selected as independent
      factors to form discriminant functions. The sensitivity, specificity and accuracy
      of this method were 94.7, 90.1 and 91.3 per cent respectively. The accuracy of
      histological analysis of frozen sections was 100 per cent. CONCLUSION: FTIR
      spectroscopy is a promising technique for the real-time diagnosis of SLN
      metastasis during breast cancer surgery. Surgical relevance Sentinel lymph node
      (SLN) biopsy is a highly accurate predictor of overall axillary status and has
      become the standard in disease staging in clinically node-negative breast cancer.
      A rapid and accurate intraoperative assessment of metastatic spread to the SLN
      provides the necessary information for the surgeon to proceed with immediate
      axillary dissection. The results of this research indicate that Fourier transform
      infrared (FTIR) spectroscopy is a rapid, accurate, non-destructive and cost
      effective molecular method that can be used to detect SLN metastasis during
      surgery. FTIR analysis could be useful for the intraoperative diagnosis of lymph
      node metastases at large institutions, thereby reducing the workload of
      pathologists, as well as in regions lacking pathologists such as in developing
      countries.

PMID- 26198698
TI  - Haemophilus parasuis infection activates chemokine RANTES in PK-15 cells.
AB  - RANTES is a member of the CC chemokine involved in inflammation and immune
      response during pathogen infection. In our previous study, Haemophilus parasuis
      (H. parasuis), which is responsible for the great economic losses in the pig
      industry worldwide, has been shown to enhance RANTES expression in PK-15 cells.
      However, the mechanisms behind this biological phenomenon have remained unclear.
      In this study, we showed that H. parasuis infection significantly upregulated
      RANTES gene transcription in a time- and dose-dependent manner. Promoter analysis
      by site-directed mutagenesis indicated that the nuclear factor NF-kappaB binding
      site was the most important cis-regulatory element controlling H. parasuis
      induced RANTES transcription. Inhibition of NF-kappaB and JNK activity also
      significantly reduced H. parasuis-induced RANTES production. In addition, TLRs
      signaling pathway was found to be involved in H. parasuis induced-RANTES
      expression. These results represent an important molecular mechanism whereby H.
      parasuis induced RANTES in the inflammatory response. 

PMID- 26198699
TI  - Invariant chain is a new chaperone for TLR7 in B cells.
AB  - The innate immune system provides the first barrier against pathogens.
      Intracellular Toll-like receptors (TLR3, 7 and 9) localise in endosomes and sense
      nucleotides from viruses and bacteria. This recognition induces their
      conformational changes resulting in the production of proinflammatory cytokines
      and MHC class II (MHCII) antigenic presentation. In the absence of stimulation,
      TLRs are retained in the endoplasmic reticulum. Upon stimulation, they relocate
      to the endo-lysosomal compartment, allowing the recruitment of the adaptor
      molecules, MyD88 or TRIF. Increasing evidences describe a cross talk between
      proteins that regulate both innate and adaptive immune responses. For example,
      proteolytic enzymes which are required for breaking down exogenous antigen to
      generate suitable peptides for MHCII molecules are also essential to activate
      endosomal TLRs and MHCII molecules were recently described to regulate TLR
      signalling. But other proteins are possibly involved and regulated differentially
      between cell types. We have observed that intracellular TLR trafficking and
      signalling in B cells are different from dendritic cells and macrophages and
      involved the MHCII chaperone molecule, the invariant chain (Ii). 

PMID- 26198700
TI  - Cyclin-dependent kinase 5 represses Foxp3 gene expression and Treg development
      through specific phosphorylation of Stat3 at Serine 727.
AB  - Cyclin-dependent kinase 5 (Cdk5) is known as a unique member of the cyclin
      dependent family of serine/threonine kinases. Previously, we demonstrated Cdk5 to
      be an important regulator of T cell function and that disruption of Cdk5
      expression ameliorates T cell mediated neuroinflammation. Here, we show a novel
      role of Cdk5 in the regulation of Foxp3 expression in murine CD4(+) T cells. Our
      data indicate that disruption of Cdk5 activity in T cells abrogates the IL-6
      suppression of Foxp3 expression. This effect is achieved through Cdk5
      phosphorylation of the signal transducer and activator of transcription 3 (Stat3)
      specifically at Serine 727 in T cells, and we show this post-translational
      modification is required for proper Stat3 DNA binding to the Foxp3 gene on the
      enhancer II region. Taken together, our data point to an essential role for Cdk5
      in the differentiation of T cells as it regulates Foxp3 gene expression through
      phosphorylation of Stat3. 

PMID- 26198701
TI  - An impedance method for spatial sensing of 3D cell constructs--towards
      applications in tissue engineering.
AB  - We present the characterisation and validation of multiplexed 4-terminal (4T)
      impedance measurements as a method for sensing the spatial location of cell
      aggregates within large three-dimensional (3D) gelatin scaffolds. The
      measurements were performed using an array of four rectangular chambers, each
      having eight platinum needle electrodes for parallel analysis. The electrode
      positions for current injection and voltage measurements were optimised by means
      of finite element simulations to maximise the sensitivity field distribution and
      spatial resolution. Eight different 4T combinations were experimentally tested in
      terms of the spatial sensitivity. The simulated sensitivity fields were validated
      using objects (phantoms) with different conductivity and size placed in different
      positions inside the chamber. This provided the detection limit (volume
      sensitivity) of 16.5%, i.e. the smallest detectable volume with respect to the
      size of the measurement chamber. Furthermore, the possibility for quick single
      frequency analysis was demonstrated by finding a common frequency of 250 kHz for
      all the presented electrode combinations. As final proof of concept, a high
      density of human hepatoblastoma (HepG2) cells were encapsulated in gelatin to
      form artificial 3D cell constructs and detected when placed in different
      positions inside large gelatin scaffolds. Taken together, these results open new
      perspectives for impedance-based sensing technologies for non-invasive monitoring
      in tissue engineering applications providing spatial information of constructs
      within biologically relevant 3D environments. 

PMID- 26198702
TI  - Probiotics for prevention of atopic diseases in infants: systematic review and
      meta-analysis.
AB  - Growing evidence underlines the pivotal role of infant gut colonization in the
      development of the immune system. The possibility to modify gut colonization
      through probiotic supplementation in childhood might prevent atopic diseases. The
      aim of the present systematic review and meta-analysis was to evaluate the effect
      of probiotic supplementation during pregnancy and early infancy in preventing
      atopic diseases. PubMed, Embase and Cochrane Library were searched for randomized
      controlled trials evaluating the use of probiotics during pregnancy or early
      infancy for prevention of allergic diseases. Fixed-effect models were used, and
      random-effects models where significant heterogeneity was present. Results were
      expressed as risk ratio (RR) with 95% confidence interval (CI). Seventeen
      studies, reporting data from 4755 children (2381 in the probiotic group and 2374
      in the control group), were included in the meta-analysis. Infants treated with
      probiotics had a significantly lower RR for eczema compared to controls (RR 0.78
      [95% CI: 0.69-0.89], P = 0.0003), especially those supplemented with a mixture of
      probiotics (RR 0.54 [95% CI: 0.43-0.68], P < 0.00001). No significant difference
      in terms of prevention of asthma (RR 0.99 [95% CI: 0.77-1.27], P = 0.95),
      wheezing (RR 1.02 [95% CI: 0.89-1.17], P = 0.76) or rhinoconjunctivitis (RR 0.91
      [95% CI: 0.67-1.23], P = 0.53) was documented. The results of the present meta
      analysis show that probiotic supplementation prevents infantile eczema, thus
      suggesting a new potential indication for probiotic use in pregnancy and infancy.

PMID- 26198703
TI  - Cytotoxicity and apoptosis induced by silver nanoparticles in human liver HepG2
      cells in different dispersion media.
AB  - Silver nanoparticles (Ag NPs) have been widely used in medical and healthcare
      products owing to their unique antibacterial activities. However, their safety
      for humans and the environment has not yet been established. This study evaluated
      the cellular proliferation and apoptosis of Ag NPs suspended in different
      solvents using human liver HepG2 cells. The ionization of Ag NPs in different
      dispersion media [deionized water, phosphate-buffered saline (PBS), saline and
      cell culture] was measured using an Ag ion selective electrode. The MTT assay was
      used to examine the cell proliferation activities. The effects of Ag NPs on cell
      cycle, induction of apoptosis, production of reactive oxygen species (ROS) and
      mitochondrial membrane potential (MMP) were analyzed using flow cytometry. The
      degree of Ag NPs ionization differed with dispersion media, with the
      concentrations of silver ions in deionized water being the highest in all
      suspensions. Ag NPs could inhibit the viability of HepG2 cells in a time- and
      concentration-dependent manner. Ag NPs (40, 80 and 160 ug ml(-1)) exposure could
      cause cell-cycle arrest in the G2/M phase, significantly increasing the apoptosis
      rate and ROS generation, and decreasing the MMP in HepG2 cells more sensitive to
      deionized water than in cell culture. These results suggested that the cellular
      toxicological mechanism of Ag NPs might be related to the oxidative stress of
      cells by the generation of ROS, leading to mitochondria injury and induction of
      apoptosis. It also implies that it is important to assess the physicochemical
      properties of NPs in the media where the biological toxicity tests are performed.

PMID- 26198704
TI  - Surgical challenges in the management of cervical kyphotic deformity in patients
      with severe osteoporosis: an illustrative case of a patient with Hajdu-Cheney
      syndrome.
AB  - PURPOSE: No standard strategy exists for the management of cervical kyphotic
      deformity in patients with severe osteoporosis. In fact, in such subpopulation,
      standard algorithms commonly used in patients with normal bone mineral density
      may not be applicable. In this Grand Rounds, the authors present a challenging
      case of a patient with Hajdu-Cheney syndrome, a rare disorder of bone metabolism
      induced by a Notch-2 mutation, who presented with cervical kyphotic deformity and
      severe osteoporosis. METHODS: A 65-year-old female patient with a previous
      diagnosis of Hajdu-Cheney syndrome presented with cervical myelopathy and
      cervical kyphotic deformity. The initial MRi demonstrated multilevel cervical
      canal stenosis. The CT-scan also revealed marked spondylolisthesis of C6 over C7
      as well as numerous laminar and pedicle fractures, resulting in a cervical
      kyphosis of approximately 50 degrees. RESULTS: The patient was submitted to 360
      degree decompression and fusion of the cervical spine consisting of a staged C6
      anterior corpectomy and multilevel microdiscectomies with wide opening of the
      posterior longitudinal ligament in order to provide a satisfactory release of
      anterior spinal structures, followed by 24 h of cervical halo-traction, a second
      anterior approach for bone graft implantation in the site of the corpectomy as
      well as insertion of allografts and completion of the ACDF C2-T1 and plating,
      and, finally, a posterior C2-T3 pedicle screw instrumentation using intra
      operative CT-scan (O-arm) navigation guidance. CONCLUSIONS: This case illustrates
      some intra-operative nuances as well as specific surgical recommendations for
      cervical deformity surgery in patients with severe osteoporosis, such as
      avoidance of Caspar pins for interbody distraction, use of intra-operative
      fluoroscopy for achievement of bicortical purchase of anterior cervical screws
      and placement of pedicle screws during posterior instrumentation. Moreover, such
      illustrative case demonstrates that, in the subpopulation of patients with severe
      osteoporosis, it may be possible to successfully apply cervical distraction after
      an isolated anterior approach with a satisfactory improvement in the cervical
      alignment, possibly avoiding more laborious 540-degree approaches such as the
      previously described back-front-back or front-back-front surgical algorithms.

PMID- 26198705
TI  - Correlation between cervical lordosis and adjacent segment pathology after
      anterior cervical spinal surgery.
AB  - PURPOSE: To evaluate the incidence and risk factors for adjacent segment
      pathology (ASP) after anterior cervical spinal surgery. METHODS: Fourteen
      patients (12 male, mean age 47.1 years) who underwent single-level cervical disk
      arthroplasty (CDA group) and 28 case-matched patients (24 male, mean age 53.6
      years) who underwent single-level anterior cervical discectomy and fusion (ACDF
      group) were included. Presence of radiologic ASP (RASP) was based on observed
      changes in anterior osteophytes, disks, and calcification of the anterior
      longitudinal ligament on lateral radiographs. RESULTS: The mean follow-up period
      was 43.4 months in the CDA group and 44.6 months in the ACDF group. At final
      follow-up, ASP was observed in 5 (35.7%) CDA patients and 16 (57.1%) ACDF
      patients (p = 0.272). The interval between surgery and ASP development was 33.8
      months in the CDA group and 16.3 months in the ACDF group (p = 0.046). The ASP
      risk factor analysis indicated postoperative cervical angle at C3-7 being more
      lordotic in non-ASP patients in both groups. Restoration of lordosis occurred in
      the CDA group regardless of the presence of ASP, but heterotopic ossification
      development was associated with the presence of ASP in the CDA group. And the CDA
      group had significantly greater clinical improvements than those in the ACDF
      group when ASP was present. CONCLUSION: In both CDA and ACDF patients, RASP
      developed, but CDA was associated with a delay in ASP development. A good
      clinical outcome was expected in CDA group, even when ASP developed. Restoration
      of cervical lordosis was an important factor in anterior cervical spine surgery.

PMID- 26198706
TI  - Preexisting severe cervical spinal cord compression is a significant risk factor
      for severe paralysis development in patients with traumatic cervical spinal cord
      injury without bone injury: a retrospective cohort study.
AB  - PURPOSE: The objective of this study is to investigate whether preexisting severe
      cervical spinal cord compression affects the severity of paralysis once patients
      develop traumatic cervical spinal cord injury (CSCI) without bone injury.
      METHODS: We retrospectively investigated 122 consecutive patients with traumatic
      CSCI without bone injury. The severity of paralysis on admission was assessed by
      the American Spinal Injury Association impairment scale (AIS). The degree of
      preexisting cervical spinal cord compression was evaluated by the maximum spinal
      cord compression (MSCC) and was divided into three categories: minor compression
      (MSCC <= 20 %), moderate compression (20 % < MSCC <= 40 %), and severe
      compression (40 % < MSCC). We investigated soft-tissue damage on magnetic
      resonance imaging to estimate the external force applied. Other potential risk
      factors, including age, sex, fused vertebra, and ossification of longitudinal
      ligament, were also reviewed. A multivariate logistic regression analysis was
      performed to investigate the risk factors for developing severe paralysis (AIS A
      C) on admission. RESULTS: Our study included 103 males and 19 females with mean
      age of 65 years. Sixty-one patients showed severe paralysis (AIS A-C) on
      admission. The average MSCC was 22 %. Moderate compression was observed in 41,
      and severe in 20. Soft-tissue damage was observed in 91. A multivariate analysis
      showed that severe cervical spinal cord compression significantly affected the
      severity of paralysis at the time of injury, whereas both mild and moderate
      compression did not affect it. Soft-tissue damage was also significantly
      associated with severe paralysis on admission. CONCLUSIONS: Preexisting severe
      cervical cord compression is an independent risk factor for severe paralysis once
      patients develop traumatic CSCI without bone injury.

PMID- 26198707
TI  - Lumbar disc herniation surgery in children: outcome and gender differences.
AB  - INTRODUCTION: Lumbar disc herniation (LDH) in children is rare. Few studies have
      evaluated the outcome of surgery and none in a prospective study design. PURPOSE:
      To evaluate preoperative disability and postoperative outcome in children
      operated on for LDH. METHODS: Through a 10-year period, 74 children aged <18
      years were included in SweSpine register for LDH with pre- and perioperative data
      registered, 48 with 1-year follow-up data. Demographics and outcome measurements
      were described according to the SweSpine protocol. RESULTS: All patients reported
      preoperatively severe impairment in terms of pain, quality of life and function,
      girls to a higher extent. Significant postoperative improvement was seen in all
      patients, leaving no patients dissatisfied with outcome. The PROMS were 1 year
      after surgery within normal ranges, but remained slightly lower for girls.
      CONCLUSION: Operative treatment of LDH in growing individuals leads to very good
      outcome with high degree of patient satisfaction.

PMID- 26198708
TI  - 'Micro-managers' of hepatic lipid metabolism and NAFLD.
AB  - Nonalcoholic fatty liver disease (NAFLD) is tightly associated with insulin
      resistance, type 2 diabetes, and obesity. As the defining feature of NAFLD,
      hepatic steatosis develops as a consequence of metabolic dysregulation of de novo
      lipogenesis, fatty acid uptake, fatty acid oxidation, and triglycerides (TG)
      export. MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs, play
      critical roles in various biological processes through regulating gene expression
      at post-transcriptional level. A growing body of evidence suggests that miRNAs
      not only maintain hepatic TG homeostasis under physiological condition, but also
      participate in the pathogenesis of NAFLD. In this review, we focus on the current
      knowledge of the hepatic miRNAs associated with the development of liver
      steatosis and the regulatory mechanisms involved, which might be helpful to
      further understand the nature of NAFLD and provide a sound scientific basis for
      the drug development.

PMID- 26198709
TI  - Top-down expectancy versus bottom-up guidance in search for known color-form
      conjunctions.
AB  - We assessed the effects of pairing a target object with its familiar color on eye
      movements in visual search, under conditions where the familiar color could or
      could not be predicted. In Experiment 1 participants searched for a yellow- or
      purple-colored corn target amongst aubergine distractors, half of which were
      yellow and half purple. Search was more efficient when the color of the target
      was familiar and early eye movements more likely to be directed to targets
      carrying a familiar color than an unfamiliar color. Experiment 2 introduced cues
      which predicted the target color at 80 % validity. Cue validity did not affect
      whether early fixations were to the target. Invalid cues, however, disrupted
      search efficiency for targets in an unfamiliar color whilst there was little cost
      to search efficiency for targets in their familiar color. These results
      generalized across items with different colors (Experiment 3). The data are
      consistent with early processes in selection being automatically modulated in a
      bottom-up manner to targets in their familiar color, even when expectancies are
      set for other colors.

PMID- 26198710
TI  - Transient twinkle perception is induced by sequential presentation of stimuli
      that flicker at frequencies above the critical fusion frequency.
AB  - The critical fusion frequency (CFF) is a threshold that represents the temporal
      limits of the human visual system. If two flickering stimuli with equal
      subjective luminances are presented simultaneously at different locations, the
      CFF is the temporal frequency above which they cannot be distinguished. However,
      when the stimuli are presented sequentially at the same position, a transient
      twinkle can be perceived around the moment of the changeover. To investigate the
      mechanism underlying this transient twinkle perception (TTP), we independently
      manipulated the luminance contrast and temporal frequency of the flicker, as well
      as the interstimulus interval (ISI). We found that TTP was greater as the
      luminance step was larger, was stably perceived for flicker frequencies up to 200
      Hz, and was robust for all ISIs if flicker frequencies were below 250 Hz. For 250
      and 300-Hz flickers, TTP was attenuated in conditions in which one-frame and two
      frame ISIs were inserted. These results can be explained by a simple filtering
      model: TTP occurs if the temporal change in the weighted moving average of
      stimulus luminance exceeds a certain threshold. TTP gives additional evidence
      that the human visual system can detect the transient change of flicker stimuli
      at much higher temporal frequencies than the CFF, by an averaging mechanism of
      luminance. 

PMID- 26198712
TI  - Science and art in retinopathy of prematurity diagnosis.

PMID- 26198711
TI  - Sex hormone-related neurosteroids differentially rescue bioenergetic deficits
      induced by amyloid-beta or hyperphosphorylated tau protein.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disease marked by a
      progressive cognitive decline. Metabolic impairments are common hallmarks of AD,
      and amyloid-beta (Abeta) peptide and hyperphosphorylated tau protein--the two
      foremost histopathological signs of AD--have been implicated in mitochondrial
      dysfunction. Neurosteroids have recently shown promise in alleviating cognitive
      and neuronal sequelae of AD. The present study evaluates the impact of
      neurosteroids belonging to the sex hormone family (progesterone, estradiol,
      estrone, testosterone, 3alpha-androstanediol) on mitochondrial dysfunction in
      cellular models of AD: human neuroblastoma cells (SH-SY5Y) stably transfected
      with constructs encoding (1) the human amyloid precursor protein (APP) resulting
      in overexpression of APP and Abeta, (2) wild-type tau (wtTau), and (3) mutant tau
      (P301L), that induces abnormal tau hyperphosphorylation. We show that while APP
      and P301L cells both display a drop in ATP levels, they present distinct
      mitochondrial impairments with regard to their bioenergetic profiles. The P301L
      cells presented a decreased maximal respiration and spare respiratory capacity,
      while APP cells exhibited, in addition, a decrease in basal respiration, ATP
      turnover, and glycolytic reserve. All neurosteroids showed beneficial effects on
      ATP production and mitochondrial membrane potential in APP/Abeta overexpressing
      cells while only progesterone and estradiol increased ATP levels in mutant tau
      cells. Of note, testosterone was more efficient in alleviating Abeta-induced
      mitochondrial deficits, while progesterone and estrogen were the most effective
      neurosteroids in our model of AD-related tauopathy. Our findings lend further
      support to the neuroprotective effects of neurosteroids in AD and may open new
      avenues for the development of gender-specific therapeutic approaches in AD.

PMID- 26198713
TI  - Insulin resistance in heart failure: differences between patients with reduced
      and preserved left ventricular ejection fraction.
AB  - AIMS: Insulin resistance (IR) is a characteristic feature of heart failure (HF)
      pathophysiology that affects symptoms and mortality. Differences in the
      pathophysiological profile of IR in HF with preserved ejection fraction (HFpEF)
      and HF with reduced ejection fraction (HFrEF) are not characterized in detail.
      The aim of this study was to evaluate features of IR in HFpEF vs. HFrEF. METHODS
      AND RESULTS: We included 18 patients with HFrEF (EF 30 +/- 11%, body mass index
      (BMI) 26.5 +/- 3.3 kg/m(2)), 22 HFpEF patients (EF 63 +/- 7%, BMI 28.6 +/- 4.8
      kg/m(2)), and 20 healthy controls of similar age, all without diabetes mellitus.
      Patients were in stable ambulatory condition and on stable medical regimens for
      HF. IR was assessed at fasting steady state by the homeostasis model assessment
      (HOMA) index and within the physiological range of insulin-glucose interactions
      by the short insulin sensitivity test (SIST). Fasting-state IR was observed in
      HFpEF and in HFrEF in comparison with controls (HOMA 1.9, interquartile range
      (IQR) 1.5-3.6 vs. HOMA 3.1, IQR 1.4-3.7 vs. controls 1.2, IQR 1.8-0.9,
      respectively; analysis of variance P < 0.001), but no statistical difference was
      observed between HFpEF and HFrEF. The dynamic test over the physiological range
      of insulin-glucose interactions revealed a more severe IR in HFrEF as compared
      with HFpEF. Thus, glucose levels remained the highest in HFrEF (76 (64-89) mg/dL)
      at the end of the SIST compared with HFpEF and controls (68 (58-79) and 56 (44
      66) mg/dL, respectively, P < 0.001). CONCLUSION: IR is present in non-diabetic
      patients with HFpEF and HFrEF. However, distinct differences in the insulin
      sensitivity characteristics in HFpEF and HFrEF become apparent by more advanced
      testing. Patients with HFrEF showed more severe IR.

PMID- 26198714
TI  - A New Dip Coating Method to Obtain Large-Surface Coatings with a Minimum of
      Solution.
AB  - A new, simple bi-phasic dip-coating method is developed. This method is
      considered as a great improvement of the technique for research, development and
      production, since expensive, rare, harmful, or time-evolving solutions can now be
      easily deposited on large surfaces and on a single side from very little amounts
      of solution. 

PMID- 26198715
TI  - The effects of anesthesia and opioids on the upper airway: A systematic review.
AB  - OBJECTIVES/HYPOTHESIS: Drug-induced sleep endoscopy (DISE) is used to determine
      surgical therapy for obstructive sleep apnea (OSA); however, the effects of
      anesthesia on the upper airway are poorly understood. Our aim was to
      systematically review existing literature on the effects of anesthetic agents on
      the upper airway. DATA SOURCES: PubMed, CINAHL, EBM reviews and Scopus (all
      indexed years). REVIEW METHODS: Inclusion criteria included English language
      articles containing original human data. Two investigators independently reviewed
      all articles for outcomes related to upper airway morphology, dynamics,
      neuromuscular response, and respiratory control. RESULTS: The initial search
      yielded 180 abstracts; 56 articles were ultimately included (total population =
      8,540). The anesthetic agents studied were: topical lidocaine, propofol,
      dexmedetomidine, midazolam, pentobarbital, sevoflurane, desflurane, ketamine, and
      opioids. Outcome measures were diverse and included imaging studies, genioglossus
      electromyography, endoscopic airway assessment, polysomnography, upper airway
      closing pressure, and clinical evidence of obstruction. All agents caused some
      degrees of airway collapse. Dexmedetomidine did not have dose-dependent effects
      when evaluated using cine magnetic resonance imaging, unlike sevoflurane,
      isoflurane, and propofol, and caused less dynamic collapse than propofol.
      CONCLUSIONS: Studies assessing the effect of anesthesia on the upper airway in
      patients with and without OSA are limited, and few compare effects between
      agents. Medications with minimal effect on respiratory control (e.g.,
      dexmedetomidine) may work best for DISE.

PMID- 26198716
TI  - Ketamine: a growing global health-care need.

PMID- 26198717
TI  - Tissue oxygen tension monitoring of organ perfusion: rationale, methodologies,
      and literature review.
AB  - Tissue oxygen tension is the partial pressure of oxygen within the interstitial
      space of an organ bed. As it represents the balance between local oxygen delivery
      and consumption at any given time, it offers a ready monitoring capability to
      assess the adequacy of tissue perfusion relative to local demands. This review
      covers the various methodologies used to measure tissue oxygen tension, describes
      the underlying physiological and pathophysiological principles, and summarizes
      human and laboratory data published to date. 

PMID- 26198718
TI  - Ductal stenting using side-branch cell dilation for aortic coarctation in high
      risk patients with hypoplastic left heart syndrome.
AB  - For high-risk neonates with hypoplastic left heart syndrome (HLHS) undergoing
      Norwood operation, the strategy of bilateral pulmonary artery banding and ductal
      stenting is risky in case of coarctation of the aorta (CoA), often resulting in
      death. Therefore, we devised a new method of ductal stenting with side-branch
      cell dilation, which could overcome the constriction of the ductal arch with CoA
      in two HLHS patients. This is the first report that presents this method and the
      results. (c) 2015 Wiley Periodicals, Inc. 

PMID- 26198720
TI  - The dilemma of continuing medical education.

PMID- 26198719
TI  - Treatment With Lopinavir/Ritonavir or Interferon-beta1b Improves Outcome of MERS
      CoV Infection in a Nonhuman Primate Model of Common Marmoset.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe disease in
      human with an overall case-fatality rate of >35%. Effective antivirals are
      crucial for improving the clinical outcome of MERS. Although a number of
      repurposed drugs, convalescent-phase plasma, antiviral peptides, and neutralizing
      antibodies exhibit anti-MERS-CoV activity in vitro, most are not readily
      available or have not been evaluated in nonhuman primates. We assessed 3
      repurposed drugs with potent in vitro anti-MERS-CoV activity (mycophenolate
      mofetil [MMF], lopinavir/ritonavir, and interferon-beta1b) in common marmosets
      with severe disease resembling MERS in humans. The lopinavir/ritonavir-treated
      and interferon-beta1b-treated animals had better outcome than the untreated
      animals, with improved clinical (mean clinical scores ?50.9%-95.0% and ?weight
      loss than the untreated animals), radiological (minimal pulmonary infiltrates),
      and pathological (mild bronchointerstitial pneumonia) findings, and lower mean
      viral loads in necropsied lung (?0.59-1.06 log10 copies/glyceraldehyde 3
      phosphate dehydrogenase [GAPDH]; P < .050) and extrapulmonary (?0.11-1.29 log10
      copies/GAPDH; P < .050 in kidney) tissues. In contrast, all MMF-treated animals
      developed severe and/or fatal disease with higher mean viral loads (?0.15-0.54
      log10 copies/GAPDH) than the untreated animals. The mortality rate at 36 hours
      postinoculation was 67% (untreated and MMF-treated) versus 0-33%
      (lopinavir/ritonavir-treated and interferon-beta1b-treated). Lopinavir/ritonavir
      and interferon-beta1b alone or in combination should be evaluated in clinical
      trials. MMF alone may worsen MERS and should not be used. 

PMID- 26198721
TI  - Use of a copolymer dressing on superficial and partial-thickness burns in a
      paediatric population.
AB  - OBJECTIVE: Despite extensive research into the treatment of partial-thickness
      burns, to date there has not been the emergence of a preeminent modality. This
      pilot study, the first such study to be performed in a burn unit in the US, was
      designed to evaluate the efficacy and outcomes of the application of copolymer
      dressing (Suprathel; PolyMedics Innovations Corporation, Stuttgart, Germany) for
      both superficial and deeper partial-thickness burns. METHOD: The copolymer
      dressing was used as a primary wound dressing to treat superficial and deep
      partial-thickness burns (average 5% total body surface area) in paediatric
      patients. Burns were debrided within 24 hours, at bedside, in the burn unit or in
      the operating room. The copolymer dressing was then applied directly to the wound
      and covered with a non-adherent second layer and an absorptive outer dressing.
      After discharge, patients were seen every 5-7 days until healed. Parameters
      evaluated included average hospital length of stay, average number of intravenous
      doses of narcotics administered, pain score at first follow-up visit, average
      time to complete re epithelialisation, incidence of burn wound infection, and
      patient/parent satisfaction on a 4-point scale. We also evaluated our experience
      with the dressing. Data were evaluated retrospectively under an Investigational
      Review Board approved protocol. RESULTS: Of the 17 patients assessed the average
      hospital length of stay was 1.4 days during which the average number of
      intravenous narcotic doses administered before copolymer dressing application was
      1.5 and after was 0.1 doses. At the first follow-up visit, average pain score was
      1.2 on a 10-point scale and the average time to re epithelialisation was 9.5
      days. There was no incidence of burn wound infection. Patient/parent satisfaction
      was average of 3.66 on a 4-point scale. The staff had found that the self
      adherence and elasticity of the dressing made it easy to apply and stay adherent,
      especially in areas of difficult contour. There were no readmissions for further
      debridement or skin grafting. CONCLUSION: Our experience shows that patients may
      be discharged shortly after the application of the copolymer dressing, with
      manageable pain scores and ease of use as determined by the caretakers high
      satisfaction. This new, fully synthetic copolymer dressing is easy to apply, does
      not require any additional antimicrobial coverage and may be used to successfully
      manage deeper partial-thickness burns, donor sites or burns in areas of contour,
      where many other dressings might not be considered or be appropriate. DECLARATION
      OF INTEREST: None declared.

PMID- 26198722
TI  - Cognitive decline after heart surgery is uncommon, review finds.

PMID- 26198723
TI  - Determinants of adherence to evidence-based therapy after acute myocardial
      infarction.
AB  - BACKGROUND: The extent to which drug adherence may be affected by patient
      characteristics remains unclear. This study investigated potential determinants
      of adherence to evidence-based cardioprotective medications in patients with
      acute myocardial infarction. DESIGN: Patient-based retrospective cohort study of
      4655 elderly one-year survivors of acute myocardial infarction, members of a
      health organization in Israel, between 2005 and 2010. METHODS: All patients
      filled at least one prescription for any key medication. Adherence was measured
      using the proportion-of-days-covered (PDC) metric and defined as PDC >= 80%.
      RESULTS: Nonadherence to aspirin, beta-blockers, angiotensin converting enzyme
      inhibitors/angiotensin receptor blockers or statins approximated 50%, and 80% for
      combined therapy of all medications. In multivariable analyses, compared with
      nonadherents to all medications, adherers to at least one medication were more
      likely to be of Jewish origin (adjusted odds ratio (AOR), 2.11; 95% confidence
      interval (CI), 1.60-2.78), inhabitants of the central or northern districts, and
      attending a cardiologist at least once during the first year of follow-up (AOR,
      1.26; 95% CI, 1.05-1.51). Increasing number of outpatient visits was associated
      with improved adherence and followed a significant dose-response gradient.
      Factors significantly associated with reduced adherence were presence of comorbid
      conditions, particularly chronic ischemic heart disease (AOR 0.69; 95% CI, 0.57
      0.83) and readmissions (AOR, 0.65; 95% CI, 0.55-0.78). Results were consistent
      when evaluating adherence to each medication separately. CONCLUSIONS: Outpatient
      adherence to recommended therapy in patients with acute myocardial infarction is
      suboptimal and is related to health services utilization. Further research is
      needed to investigate patient subjective behavioral-related drivers for
      medication therapy discontinuation after myocardial infarction in the absence of
      a clinical reason.

PMID- 26198724
TI  - Longitudinal Study of Body Mass Index in Young Males and the Transition to
      Fatherhood.
AB  - Despite a growing understanding that the social determinants of health have an
      impact on body mass index (BMI), the role of fatherhood on young men's BMI is
      understudied. This longitudinal study examines BMI in young men over time as they
      transition from adolescence into fatherhood in a nationally representative
      sample. Data from all four waves of the National Longitudinal Study of Adolescent
      Health supported a 20-year longitudinal analysis of 10,253 men beginning in 1994.
      A "fatherhood-year" data set was created and changes in BMI were examined based
      on fatherhood status (nonfather, nonresident father, resident father), fatherhood
      years, and covariates. Though age is positively associated with BMI over all
      years for all men, comparing nonresident and resident fathers with nonfathers
      reveals different trajectories based on fatherhood status. Entrance into
      fatherhood is associated with an increase in BMI trajectory for both nonresident
      and resident fathers, while nonfathers exhibit a decrease over the same period.
      In this longitudinal, population-based study, fatherhood and residence status
      play a role in men's BMI. Designing obesity prevention interventions for young
      men that begin in adolescence and carry through young adulthood should target the
      distinctive needs of these populations, potentially improving their health
      outcomes.

PMID- 26198725
TI  - Local delivery of a selective androgen receptor modulator failed as an anabolic
      agent in a rat bone marrow ablation model.
AB  - BACKGROUND AND PURPOSE: Selective androgen receptor modulators (SARMs) have been
      developed to have systemic anabolic effects on bones and muscles without the
      adverse effects of steroidal androgens. One unexplored therapeutic option is the
      targeted application of SARMs for the enhancement of local new bone formation. We
      evaluated the osteogenic efficacy of a locally released SARM (ORM-11984).
      METHODS: ORM-11984 was mixed with a copolymer of L-lactide and E-caprolactone
      (PLCL). An in vitro dissolution test confirmed the sustainable release of ORM
      11984 from the matrix. A bone marrow ablation model was used in female Sprague
      Dawley rats. Implants containing 10%, 30%, or 50% ORM-11984 by weight or pure
      PLCL were inserted into the medullary canal of the ablated tibia. At 6 and 12
      weeks, the volume of intramedullary new bone and the perimeter of bone-implant
      contact were measured by micro-computed tomography and histomorphometry. RESULTS:
      Contrary to our hypothesis, there was a negative correlation between the amount
      of new bone around the implant and the dose of ORM-11984. There was only a mild
      (and not statistically significant) enhancement of bone formation in ablated
      bones subjected to the lowest dose of the SARM (10%). INTERPRETATION: This study
      suggests that intramedullary/endosteal osteogenesis had a negative, dose
      dependent response to locally released SARM. This result highlights the
      complexity of androgenic effects on bones and also suggests that there are
      biological limits to the targeted local application of SARMs.

PMID- 26198727
TI  - Patterned arrays of lateral heterojunctions within monolayer two-dimensional
      semiconductors.
AB  - The formation of semiconductor heterojunctions and their high-density integration
      are foundations of modern electronics and optoelectronics. To enable two
      dimensional crystalline semiconductors as building blocks in next-generation
      electronics, developing methods to deterministically form lateral heterojunctions
      is crucial. Here we demonstrate an approach for the formation of lithographically
      patterned arrays of lateral semiconducting heterojunctions within a single two
      dimensional crystal. Electron beam lithography is used to pattern MoSe2 monolayer
      crystals with SiO2, and the exposed locations are selectively and totally
      converted to MoS2 using pulsed laser vaporization of sulfur to form MoSe2/MoS2
      heterojunctions in predefined patterns. The junctions and conversion process are
      studied by Raman and photoluminescence spectroscopy, atomically resolved scanning
      transmission electron microscopy and device characterization. This demonstration
      of lateral heterojunction arrays within a monolayer crystal is an essential step
      for the integration of two-dimensional semiconductor building blocks with
      different electronic and optoelectronic properties for high-density, ultrathin
      devices. 

PMID- 26198726
TI  - Serum protein gamma-glutamyl hydrolase, Ig gamma-3 chain C region, and
      haptoglobin are associated with the syndromes of pulmonary tuberculosis in
      traditional Chinese medicine.
AB  - BACKGROUND: Traditional Chinese Medicine (TCM) has been applied in treating
      tuberculosis (TB) based on the TCM syndromes with the effects of inhibiting
      Mycobacterium, strengthening the body immune system, and reducing the pulmonary
      toxicity. We used bioinformatic methods to study the clinical and pathological
      characteristics of pulmonary TB patients with TCM syndromes. Isobaric tags for
      relative and absolute quantification - coupled two dimensional liquid
      chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS) methods were applied
      to screen differentially expressed serum proteins. METHODS: Pulmonary TB cases
      were divided into four distinctive TCM syndromes: pulmonary Yin deficiency (PYD)
      syndrome, hyperactivity of fire due to Yin deficiency (HFYD) syndrome, deficiency
      of Qi and Yin (DQY) syndrome, and deficiency of Yin and Yang (DYY) syndrome. The
      serum samples from 214 pulmonary TB patients were collected, and the clinical and
      pathological data was analyzed by using iTRAQ-2DLC-MS/MS. Finally, the
      differentially expressed proteins were screened and tested by ELISA. Only 5
      patients with DYY syndrome were recruited in 3 years, which were not enough for
      further research. RESULTS: The DQY cases had higher erythrocyte sedimentation
      rate (ESR) compared to the PYD and HFYD cases (P=0.0178). 94.44% (12 PYD, 18
      HFYD, and 4 DQY before anti-TB treatment) of 36 treated TB cases were transformed
      to PYD accompanied with the reduction of ESR and absorption of pulmonary lesions.
      A total of 39 differentially expressed proteins (ratios of >1.3 or <0.75) were
      found among the three TCM syndromes. Proteomic studies revealed that gamma
      glutamyl hydrolase (GGH), Ig gamma-3 chain C region (IGHG3), and haptoglobin
      (HPT) were specifically over-expressed in PYD (P<0.01), HFYD (P<0.001), and DQY
      cases (P<0.01), respectively. Furthermore, GGH was significantly higher in PYD
      cases compared to the HFYD and DQY cases (P<0.01, P<0.001, respectively), whereas
      IGHG3 was significantly higher in HFYD cases than PYD and DQY cases (P<0.001,
      P<0.01, respectively). CONCLUSIONS: The results suggest that TCM syndromes are
      significantly correlated with the pulmonary lesions and ESR. GGH was associated
      with folate metabolism in PYD cases, IGHG3 was linked to the control of
      Mycobacterium infection in HFYD patients, and HPT was involved in hypoxia in DQY
      patients. The present study provides new biological basis to understand the
      pathological changes and proteomic differences of TB syndromes.

PMID- 26198728
TI  - Intranasal cross-sectional area and quality of life changes following endoscopic
      transsphenoidal skull base surgery.
AB  - BACKGROUND: Endoscopic transsphenoidal surgical approaches to the skull base may
      produce alteration of intranasal architecture. Acoustic rhinometry (AR) can
      provide quantitative data on the nasal airway, which has not been previously
      applied to skull base surgery. We sought to employ AR to quantify the changes in
      nasal patency following endoscopic transsphenoidal surgery and identify the
      relationship between these changes and septal deviation, nasoseptal flap harvest,
      and sinonasal quality of life (QOL). METHODS: Consecutive patients undergoing
      endoscopic transsphenoidal resection of a sellar or suprasellar tumor were
      prospectively enrolled. All subjects were adults who completed AR and the 22-item
      Sino-Nasal Outcome Test (SNOT-22) preoperatively and postoperatively. Cross
      sectional area (CSA) was recorded at the internal nasal valve (CSA1), middle
      turbinate head (CSA2), and middle turbinate body (CSA3). Normative data were also
      collected from a larger cohort. RESULTS: Forty patients met study criteria.
      Significant increases occurred postoperatively in mean CSA2 (1.08 cm(2)) and CSA3
      (2.47 cm(2)) (p < 0.001), whereas CSA1 remained unchanged. Nasoseptal flap
      harvest and correction of septal deviation did not significantly alter mean
      postoperative AR values. Mean SNOT-22 scores were comparable despite septal
      pathology, whereas strong correlation was not found with change in AR values.
      Preoperative and postoperative QOL scores were not significantly affected by the
      presence of nasal septal deviation. CONCLUSION: The endoscopic transsphenoidal
      approach to the skull base can result in increased intranasal area without a
      detrimental effect on sinonasal QOL. These effects are independent of nasoseptal
      flap harvest and correction of nasal septal deviation.

PMID- 26198731
TI  - A versatile class of prototype dynamical systems for complex bifurcation cascades
      of limit cycles.
AB  - A general class of prototype dynamical systems is introduced, which allows to
      study the generation of complex bifurcation cascades of limit cycles, including
      bifurcations breaking spontaneously a symmetry of the system, period doubling and
      homoclinic bifurcations, and transitions to chaos induced by sequences of limit
      cycle bifurcations. The prototype systems are adaptive, with friction forces
      f(V(x)) being functionally dependent exclusively on the mechanical potential
      V(x), characterized in turn by a finite number of local minima. We discuss
      several low-dimensional systems, with friction forces f(V) which are linear,
      quadratic or cubic polynomials in the potential V. We point out that the zeros of
      f(V) regulate both the relative importance of energy uptake and dissipation
      respectively, serving at the same time as bifurcation parameters, hence allowing
      for an intuitive interpretation of the overall dynamical behavior. Starting from
      simple Hopf- and homoclinic bifurcations, complex sequences of limit cycle
      bifurcations are observed when the energy uptake gains progressively in
      importance. 

PMID- 26198729
TI  - Expression and Significances of MTSS1 in Pancreatic Cancer.
AB  - Thus far, expression of metastasis suppressor 1 (MTSS1), its clinicopathologic
      and prognostic significances in pancreatic cancer (PC) remain unknown. Expression
      of MTSS1 was detected by Western blotting in PC cell lines, and by tissue
      microarray-based immunohistochemical staining in paired tumor and non-tumor
      samples from 242 patients with PC. Furthermore, the correlations between MTSS1
      expression and clinicopathologic variables as well as overall survival were
      evaluated. In PC cell lines, MTSS1 was differentially expressed. In addition,
      MTSS1 expression was significantly lower in tumor than in non-tumor tissues (P <
      0.001 in both McNemar and Mann-Whitney U tests). High tumoral expression of MTSS1
      was closely associated with absence of lymph node metastasis (P = 0.023).
      Univariate analysis found that high MTSS1 expression in tumor tissues was a
      strong predictor of favorable overall survival in the whole cohort (P < 0.001).
      Besides, its impacts on prognosis were also observed in nine out of fourteen
      subgroups. Finally, MTSS1 expression was identified as an independent prognostic
      marker in the whole cohort (P = 0.031) as well as in six subgroups (P < 0.05), as
      shown by multivariate Cox regression test. Down-regulation of MTSS1 expression is
      evident in PC, and is associated with lymph node metastasis and poor prognosis. 

PMID- 26198732
TI  - Structural deficits and cognitive impairment in tuberculous meningitis.
AB  - BACKGROUND: Chronic neuropsychological sequelae may occur in patients with
      tuberculous meningitis (TBM). The impact of structural abnormalities on the
      clinical performance of patients with TBM is unknown. This study applied the
      Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL)
      voxel-based morphometry (VBM) to determine if gray matter deficits in TBM are
      associated with acute presentations and chronic cognitive impairment. METHODS:
      Seventeen patients with TBM who discontinued their anti-TB therapy for more than
      six months, and 17 age-, sex-, and education-matched healthy subjects were
      enrolled. Differences in gray matter volume (GMV) between patients and healthy
      controls were investigated using DARTEL-VBM to determine structural
      abnormalities. Disease severity during the acute stage was scored by clinical
      profiles and conventional imaging findings. Correlations among chronic structural
      deficits, cognitive impairment, and initial disease severity were assessed.
      RESULTS: The patients with TBM had worse neuropsychological subtest performances
      than the healthy controls. Compared to the controls, the patients showed smaller
      GMVs in the right thalamus, right caudate nucleus, right superior and middle
      temporal gyrus, right precuneus, and left putamen (p < 0.001). The smaller GMVs
      in the right thalamus, right superior temporal gyrus, right precuneus, left
      putamen, and right caudate nucleus (p < 0.05) were further associated with worse
      cognitive function. More severe initial disease also correlated with smaller GMVs
      in the right caudate nucleus (p < 0.05). CONCLUSION: Multiple domain cognitive
      impairment may persist in patients with chronic TBM even after appropriate
      treatment. Worse initial disease severity may contribute to the vulnerability of
      brain tissue to damage, with subsequent neuropsychological consequences.

PMID- 26198733
TI  - A novel HLA-DQ allele, HLA-DQB1*05:48, found in the Saudi Stem Cells Donor
      Registry.
AB  - The allele HLA-DQB1*05:48 differs from HLA-DQB1*05:01:01 by a non-synonymous T to
      C substitution at nucleotide position 1693 in exon 2. 

PMID- 26198734
TI  - CSF TNFalpha Has Not Been Shown to be Elevated in Headache Patients.

PMID- 26198735
TI  - Child personality facets and overreactive parenting as predictors of aggression
      and rule-breaking trajectories from childhood to adolescence.
AB  - This study examined trajectories of aggression and rule breaking during the
      transition from childhood to adolescence (ages 9-15), and determined whether
      these trajectories were predicted by lower order personality facets, overreactive
      parenting, and their interaction. At three time points separated by 2-year
      intervals, mothers and fathers reported on their children's aggression and rule
      breaking (N = 290, M age = 8.8 years at Time 1). At Time 1, parents reported on
      their children's personality traits and their own overreactivity. Growth mixture
      modeling identified three aggression trajectories (low decreasing, high
      decreasing, and high increasing) and two rule-breaking trajectories (low and
      high). Lower optimism and compliance and higher energy predicted trajectories for
      both aggression and rule breaking, whereas higher expressiveness and irritability
      and lower orderliness and perseverance were unique risk factors for increasing
      aggression into adolescence. Lower concentration was a unique risk factor for
      increasing rule breaking. Parental overreactivity predicted higher trajectories
      of aggression but not rule breaking. Only two Trait * Overreactivity interactions
      were found. Our results indicate that personality facets could differentiate
      children at risk for different developmental trajectories of aggression and rule
      breaking. 

PMID- 26198737
TI  - Groundwater Arsenic Adsorption on Granular TiO2: Integrating Atomic Structure,
      Filtration, and Health Impact.
AB  - A pressing challenge in arsenic (As) adsorptive filtration is to decipher how the
      As atomic surface structure obtained in the laboratory can be used to accurately
      predict the field filtration cycle. The motivation of this study was therefore to
      integrate molecular level As adsorption mechanisms and capacities to predict
      effluent As from granular TiO2 columns in the field as well as its health
      impacts. Approximately 2,955 bed volumes of groundwater with an average of 542
      MUg/L As were filtered before the effluent As concentration exceeded 10 MUg/L,
      corresponding to an adsorption capacity of 1.53 mg As/g TiO2. After regeneration,
      the TiO2 column could treat 2,563 bed volumes of groundwater, resulting in an As
      load of 1.36 mg/g TiO2. Column filtration and EXAFS results showed that among
      coexisting ions present in groundwater, only Ca(2+), Si(OH)4, and HCO3(-) would
      interfere with As adsorption. The compound effects of coexisting ions and
      molecular level structural information were incorporated in the PHREEQC program
      to satisfactorily predict the As breakthrough curves. The total urinary As
      concentration from four volunteers of local residences, ranging from 972 to 2,080
      MUg/L before groundwater treatment, decreased to the range 31.7-73.3 MUg/L at the
      end of the experimental cycle (15-33 days).

PMID- 26198738
TI  - Correction to: Panobinostat: a novel pan-deacetylase inhibitor for the treatment
      of relapsed or relapsed and refractory multiple myeloma.

PMID- 26198736
TI  - A combinational approach of multilocus sequence typing and other molecular typing
      methods in unravelling the epidemiology of Erysipelothrix rhusiopathiae strains
      from poultry and mammals.
AB  - Erysipelothrix rhusiopathiae infections re-emerged as a matter of great concern
      particularly in the poultry industry. In contrast to porcine isolates, molecular
      epidemiological traits of avian E. rhusiopathiae isolates are less well known.
      Thus, we aimed to (i) develop a multilocus sequence typing (MLST) scheme for E.
      rhusiopathiae, (ii) study the congruence of strain grouping based on pulsed-field
      gel electrophoresis (PFGE) and MLST, (iii) determine the diversity of the
      dominant immunogenic protein SpaA, and (iv) examine the distribution of genes
      putatively linked with virulence among field isolates from poultry (120), swine
      (24) and other hosts (21), including humans (3). Using seven housekeeping genes
      for MLST analysis we determined 72 sequence types (STs) among 165 isolates. This
      indicated an overall high diversity, though 34.5% of all isolates belonged to a
      single predominant ST-complex, STC9, which grouped strains from birds and
      mammals, including humans, together. PFGE revealed 58 different clusters and
      congruence with the sequence-based MLST-method was not common. Based on
      polymorphisms in the N-terminal hyper-variable region of SpaA the isolates were
      classified into five groups, which followed the phylogenetic background of the
      strains. More than 90% of the isolates harboured all 16 putative virulence genes
      tested and only intI, encoding an internalin-like protein, showed infrequent
      distribution. MLST data determined E. rhusiopathiae as weakly clonal species with
      limited host specificity. A common evolutionary origin of isolates as well as
      shared SpaA variants and virulence genotypes obtained from avian and mammalian
      hosts indicates common reservoirs, pathogenic pathways and immunogenic properties
      of the pathogen.

PMID- 26198739
TI  - Why is microRNA action tissue specific? A putative defense mechanism against
      growth disorders, tumor development or progression mediated by circulating
      microRNA?
AB  - MicroRNAs as endogenous mediators of RNA interference and epigenetic regulation
      are involved in the regulation of numerous basic physiological processes. Both
      their expression and action is tissue specific, as microRNA target different
      messenger RNA molecules in different tissues and have various actions. MicroRNAs
      are major players in tumor development and act as oncogenes and tumor suppressors
      that also depend on the cellular context. MicroRNA are secreted and are present
      in the circulation, and circulating microRNA might affect gene expression in
      various cells. We present a hypothesis on the relevance of tissue specific
      microRNA action supposing that it might be a putative defense mechanism
      preventing secreted microRNA-mediated uniform gene expression changes (e.g.
      inducing cell proliferation or inhibiting apoptosis) and thus growth disorders,
      tumor development or progression that would occur if all cells and tissues would
      respond in the same way to circulating microRNA. 

PMID- 26198740
TI  - Fibromyalgia syndrome in Turkish hemodialysis patients.
AB  - The aim of our study was to evaluate the frequency of fibromyalgia syndrome (FMS)
      in hemodialysis (HD) patients and to assess whether this syndrome is associated
      with gender, age, duration of HD, or various laboratory parameters. This study
      was composed of 221 chronic HD patients (99 females and 122 males), and we
      recorded each participant's age, gender, causes of kidney failure, HD duration,
      education level, and symptoms related to FMS, which was diagnosed according to
      the 2010 American College of Rheumatology criteria. We documented the laboratory
      parameters for all patients. In addition, patients with FMS filled out the
      Fibromyalgia Impact Questionnaire. Twenty-two patients met the diagnostic
      criteria for FMS (9%), and there were no statistically significant differences
      related to age, gender, or HD duration between FMS and non-FMS groups (P > 0.05).
      In addition, the education levels were lower in patients diagnosed with FMS (P <
      0.05), and there were statistically significant differences related to sleep
      disturbance, fatigue, and cognitive symptoms between the two groups (P < 0.05) as
      well. However, their laboratory parameters were similar (P > 0.05). There was a
      higher prevalence of FMS in HD patients than in the general population. Sleep
      disturbances, fatigue, education level, and cognitive symptoms were associated
      with FMS, but there was no correlation between the laboratory parameters and this
      condition. 

PMID- 26198741
TI  - Direct experimental observation of weakly-bound character of the attached
      electron in europium anion.
AB  - Direct experimental determination of precise electron affinities (EAs) of
      lanthanides is a longstanding challenge to experimentalists. Considerable debate
      exists in previous experiment and theory, hindering the complete understanding
      about the properties of the atomic anions. Herein, we report the first precise
      photoelectron imaging spectroscopy of europium (Eu), with the aim of eliminating
      prior contradictions. The measured EA (0.116 +/- 0.013 eV) of Eu is in excellent
      agreement with recently reported theoretical predictions, providing direct
      spectroscopic evidence that the additional electron is weakly attached.
      Additionally, a new experimental strategy is proposed that can significantly
      increase the yield of the lanthanide anions, opening up the best opportunity to
      complete the periodic table of the atomic anions. The present findings not only
      serve to resolve previous discrepancy but also will help in improving the depth
      and accuracy of our understanding about the fundamental properties of the atomic
      anions. 

PMID- 26198743
TI  - Unique and conserved genome regions in Vibrio harveyi and related species in
      comparison with the shrimp pathogen Vibrio harveyi CAIM 1792.
AB  - Vibrio harveyi CAIM 1792 is a marine bacterial strain that causes mortality in
      farmed shrimp in north-west Mexico, and the identification of virulence genes in
      this strain is important for understanding its pathogenicity. The aim of this
      work was to compare the V. harveyi CAIM 1792 genome with related genome sequences
      to determine their phylogenic relationship and explore unique regions in silico
      that differentiate this strain from other V. harveyi strains. Twenty-one newly
      sequenced genomes were compared in silico against the CAIM 1792 genome at
      nucleotidic and predicted proteome levels. The proteome of CAIM 1792 had higher
      similarity to those of other V. harveyi strains (78%) than to those of the other
      closely related species Vibrio owensii (67%), Vibrio rotiferianus (63%) and
      Vibrio campbellii (59%). Pan-genome ORFans trees showed the best fit with the
      accepted phylogeny based on DNA-DNA hybridization and multi-locus sequence
      analysis of 11 concatenated housekeeping genes. SNP analysis clustered 34/38
      genomes within their accepted species. The pangenomic and SNP trees showed that
      V. harveyi is the most conserved of the four species studied and V. campbellii
      may be divided into at least three subspecies, supported by intergenomic distance
      analysis. blastp atlases were created to identify unique regions among the
      genomes most related to V. harveyi CAIM 1792; these regions included genes
      encoding glycosyltransferases, specific type restriction modification systems and
      a transcriptional regulator, LysR, reported to be involved in virulence,
      metabolism, quorum sensing and motility.

PMID- 26198742
TI  - Scrutinizing the immune defence inventory of Camponotus floridanus applying total
      transcriptome sequencing.
AB  - BACKGROUND: Defence mechanisms of organisms are shaped by their lifestyle,
      environment and pathogen pressure. Carpenter ants are social insects which live
      in huge colonies comprising genetically closely related individuals in high
      densities within nests. This lifestyle potentially facilitates the rapid spread
      of pathogens between individuals. In concert with their innate immune system,
      social insects may apply external immune defences to manipulate the microbial
      community among individuals and within nests. Additionally, carpenter ants carry
      a mutualistic intracellular and obligate endosymbiotic bacterium, possibly
      maintained and regulated by the innate immune system. Thus, different selective
      forces could shape internal immune defences of Camponotus floridanus. RESULTS:
      The immune gene repertoire of C. floridanus was investigated by re-evaluating its
      genome sequence combined with a full transcriptome analysis of immune challenged
      and control animals using Illumina sequencing. The genome was re-annotated by
      mapping transcriptome reads and masking repeats. A total of 978 protein sequences
      were characterised further by annotating functional domains, leading to a change
      in their original annotation regarding function and domain composition in about
      8% of all proteins. Based on homology analysis with key components of major
      immune pathways of insects, the C. floridanus immune-related genes were compared
      to those of Drosophila melanogaster, Apis mellifera, and other hymenoptera. This
      analysis revealed that overall the immune system of carpenter ants comprises many
      components found in these insects. In addition, several C. floridanus specific
      genes of yet unknown functions but which are strongly induced after immune
      challenge were discovered. In contrast to solitary insects like Drosophila or the
      hymenopteran Nasonia vitripennis, the number of genes encoding pattern
      recognition receptors specific for bacterial peptidoglycan (PGN) and a variety of
      known antimicrobial peptide (AMP) genes is lower in C. floridanus. The
      comparative analysis of gene expression post immune-challenge in different
      developmental stages of C. floridanus suggests a stronger induction of immune
      gene expression in larvae in comparison to adults. CONCLUSIONS: The comparison of
      the immune system of C. floridanus with that of other insects revealed the
      presence of a broad immune repertoire. However, the relatively low number of PGN
      recognition proteins and AMPs, the identification of Camponotus specific putative
      immune genes, and stage specific differences in immune gene regulation reflects
      Camponotus specific evolution including adaptations to its lifestyle.

PMID- 26198744
TI  - Evaluating a selective prevention program for substance use and comorbid
      behavioral problems in adolescents with mild to borderline intellectual
      disabilities: Study protocol of a randomized controlled trial.
AB  - BACKGROUND: Substance use and abuse is a growing problem among adolescents with
      mild to borderline intellectual disabilities (ID). Substance use patterns in
      general population are similar to patterns among non-disabled peers, but
      substance use has more negative consequences for adolescents with mild to
      borderline ID, and they are at an increased risk for developing a substance use
      disorder. Nevertheless, effective and evidence based prevention programs for this
      groups are lacking. The study described in this protocol tested the effectiveness
      of a selective intervention aimed at reducing substance use in adolescents with
      mild to borderline ID and behavioral problems. In the intervention, participants
      acquire competences to deal with their high-risk personality traits. METHODS: A
      randomized controlled trial will be conducted among 14-21-year old adolescents
      with mild to borderline ID and behavioral problems admitted to treatment
      facilities in the Netherlands. Inclusion criteria are previous substance use and
      personality risk for substance use. Participants will be individually randomized
      to the intervention (n = 70) or control (n = 70) groups. The intervention group
      will be exposed to six individual sessions and five group sessions carried out by
      two qualified trainers over six-week period. Primary outcomes will be the
      percentage reduction in substance use (for alcohol: percentage decrease of binge
      drinking, weekly use and problematic use, for cannabis: the percentage decrease
      of lifetime cannabis use and weekly use and for hard drug: the percentage
      decrease of lifetime use). Secondary outcomes will be motives for substance use,
      intention to use, and internalizing and externalizing behavioral problems. All
      outcome measures will be assessed after two, six, and twelve months after the
      intervention. DISCUSSION: This study protocol describes the design of an
      effectiveness study of a selective prevention program for substance use in
      adolescents with mild to borderline ID and behavioral problems. We expect a
      significant reduction in alcohol, cannabis and hard drug use among adolescents in
      the intervention group compared with the control group. TRIAL REGISTRATION: This
      trial is registered in the Dutch Trial Register (Cochrane Collaboration) as
      NTR5037 registered at 15 April 2015.

PMID- 26198745
TI  - Glandular differentiation in dedifferentiated chondrosarcoma: molecular evidence
      of a rare phenomenon.
AB  - Epithelial glandular differentiation in dedifferentiated chondrosarcoma has not
      been described. Our patient was a 64-year-old man with a history of prostate
      cancer status post-radiation and hormonal therapy. On screening bone scan, he was
      found to have increased uptake in his right femoral shaft. Biopsy revealed
      intermediate-grade conventional chondrosarcoma. Subsequent femoral resection was
      remarkable for an intermediate-grade chondrosarcomatous component juxtaposed to
      an area composed of anastomosing nests and cords of malignant epithelial cells
      showing nuclear atypia and increased mitotic activity. A fibroblastic-appearing
      spindle cell population was intimately associated with the epithelial cells. The
      epithelial cells labeled with 34bE12, AE1/AE3, EMA, and Vimentin (both spindled
      and epithelial components) while being negative for prostate-specific antigen,
      prostate specific acid phosphatase, cytokeratin 20, thyroid transcription factor
      1, and CDX2. The patient developed local recurrence 9 months after the initial
      resection but has had no metastatic disease and consistently undetectable
      prostate-specific antigen levels. Deep parallel sequencing of the
      dedifferentiated component showed a nonsynonymous mutation at exon 4 of IDH1 gene
      at codon R132 leading to a substitution of arginine, with serine confirming
      glandular differentiation in dedifferentiated chondrosarcoma. 

PMID- 26198746
TI  - Sarcina, a new threat in the bariatric era.
AB  - First identified in humans by Goodsir in 1842, Sarcina were already known to
      cause fatal abomasal bloat in animals. Their pathogenicity in humans has only
      recently been characterized. Sarcina is not inherently pathogenic but, with a
      gastric ulcer and delayed gastric emptying, can result in perforation. We present
      a case report of a 32-year-old woman status post-gastric banding presenting with
      epigastric pain. Upper endoscopy revealed a gastric ulcer near the band. After
      deflation, upper gastrointestinal series showed passage of contrast and no
      perforation. Ulcer biopsy showed gastric contents composed of Sarcina. Proton
      pump inhibitors and antibiotics were administered. Follow-up endoscopy at an
      outside institution resulted in perforation. This case report supports a growing
      body of literature that Sarcina organisms contribute to ulcers and perforation.
      This is the first report of Sarcina in elective bariatric surgery patients,
      highlighting the high suspicion needed among pathologists evaluating ulcers in
      this unique surgical population. 

PMID- 26198747
TI  - Parental Influence on Their Adult Children's Sexual Values: A Multi-National
      Comparison Between the United States, Spain, Costa Rica, and Peru.
AB  - We examined the influence of perceived parental sexual values, religiosity, and
      family environment on young adults' sexual values from the United States (n =
      218), Spain (n = 240), Costa Rica (n = 172), and Peru (n = 105). On average, and
      across the four national groups, the messages young adults received from their
      parents about broad domains of sexual behaviors (masturbation, non-intercourse
      types of heterosexual sexual activity, premarital sex, same-sex activity, and
      cohabiting) were unequivocally restrictive. By contrast, across the four groups,
      young adults on average held rather permissive sexual values and their values
      differed significantly from those of their parents. Moreover, the nature of
      perceived parental sexual values (restrictive vs. permissive) was not associated
      significantly with young adults' sexual values, age of sexual debut, or number of
      sexual partners. Comparatively, Spanish young adults held the most permissive
      sexual values, whereas US young adults held the most restrictive sexual values.
      Religiosity was the strongest predictor of young adults' sexual values, followed
      by perceived parental sexual values and influence. In conclusion, it appears that
      despite having perceived restrictive parental messages about sex, these young
      adults currently hold permissive sexual attitudes, thus calling into question the
      influence parents actually have on their adult children's sexual values.

PMID- 26198748
TI  - Experiences regarding maternal age-specific risks and prenatal testing of women
      of advanced maternal age in Japan.
AB  - The number of pregnant women of advanced maternal age has increased worldwide.
      Women in this group have an increased chance of fetal abnormality. To explore
      Japanese women's experiences regarding maternal age-specific risks and prenatal
      testing, we conducted a descriptive qualitative study. Semi-structured interviews
      were conducted with 16 women aged 35 years or over who had given birth within the
      previous three months to a healthy, term infant. Thematic analysis of transcribed
      interview data was performed and three major themes were identified: inadequate
      understanding of genetic risks; insufficiently informed choice regarding prenatal
      testing; and need for more information from health professionals. Some
      participants were not aware of maternal age-specific risks to the fetus. Many
      took their cues from health professionals and did not raise the topic themselves,
      but would have considered prenatal testing if made aware of the risks. Nurses,
      midwives and other health professionals need to adequately inform pregnant women
      about the genetic risks to the fetus and offer testing at an appropriate stage
      early in the pregnancy. 

PMID- 26198751
TI  - Production of transgenic cattle highly expressing human serum albumin in milk by
      phiC31 integrase-mediated gene delivery.
AB  - Transgenic cattle expressing high levels of recombinant human serum albumin (HSA)
      in their milk may as an alternative source for commercial production. Our
      objective was to produce transgenic cattle highly expressing HSA in milk by using
      phiC31 integrase system and somatic cell nuclear transfer (SCNT). The mammary
      specific expression plasmid pIACH(-), containing the attB recognition site for
      phiC31 integrase, were co-transfected with integrase expression plasmid pCMVInt
      into bovine fetal fibroblast cells (BFFs). PhiC31 integrase-mediated integrations
      in genome of BFFs were screened by nested inverse PCR. After analysis of sequence
      of the PCR products, 46.0% (23/50) of the both attB-genome junction sites (attL
      and attR) were confirmed, and four pseudo attP sites were identified. The
      integration rates in BF3, BF11, BF19 and BF4 sites were 4.0% (2/50), 6.0% (3/50),
      16.0% (8/50) and 20.0% (10/50), respectively. BF3 is located in the bovine
      chromosome 3 collagen alpha-3 (VI) chain isomer 2 gene, while the other three
      sites are located in the non-coding region. The transgenic cell lines from BF11,
      BF19 and BF4 sites were used as donors for SCNT. Two calves from transgenic cells
      BF19 were born, one died within a few hours after birth, and another calf
      survived healthy. PCR and Southern blot analysis revealed integration of the
      transgene in the genome of cloned calves. The nested reverse PCR confirmed that
      the integration site in cloned calves was identical to the donor cells. The
      western blotting assessment indicated that recombinant HSA was expressed in the
      milk of transgenic cattle and the expression level was about 4-8 mg/mL. The
      present study demonstrated that phiC31 integrase system was an efficient and
      safety gene delivery tool for producing HSA transgenic cattle. The production of
      recombinant HSA in the milk of cattle may provide a large-scale and cost
      effective resource.

PMID- 26198750
TI  - A nomogram predicting the cancer-specific mortality in patients eligible for
      radical cystectomy evaluating clinical data and neoadjuvant cisplatinum-based
      chemotherapy.
AB  - PURPOSE: Despite the increasing number of studies confirming the importance of
      neoadjuvant chemotherapy (NC) in patients before radical cystectomy (RC) for
      bladder cancer (BCa), NC remains underused. The aim of our study was to develop a
      nomogram predicting the cancer-specific mortality (CSM) of patients who underwent
      RC for transitional BCa, evaluating the available clinical information and the
      NC. MATERIALS AND METHODS: We identified 423 patients who underwent RC and pelvic
      lymph node dissection, treated or not with NC, in two European high-volume
      centers between 2007 and 2013. Chi-square and Student's t tests were used to
      evaluate differences between groups. Kaplan-Meier curves were used to assess time
      to cancer-specific (CSS) and overall survival (OS). Uni- (UVA) and multivariable
      (MVA) Cox regression analyses were developed to address predictors of CSS and OS.
      A nomogram based on the Cox regression coefficient was developed to show the
      impact of NC on CSM. RESULTS: Mean follow-up was 20.3 months. Our population had
      mainly pT2 disease (77.1%), and 19.4% had preoperative cisplatinum-based NC. NC
      showed better CSS at UVA (p = 0.014) and MVA (odds ratio: 0.44; p = 0.043).
      Overall, the 3-year OS and the CSS rate were 69.3 and 79%, respectively. The
      nomogram developed to predict the 36-month CSM showed predictive accuracy of 67%.
      CONCLUSIONS: We developed the first nomogram predicting the 36-month CSM rate in
      patients with high-risk BCa according to the clinical data. Moreover, we
      demonstrate that preoperative cisplatinum-based chemotherapy is associated with
      better CSS.

PMID- 26198749
TI  - 3-BrPA eliminates human bladder cancer cells with highly oncogenic signatures via
      engagement of specific death programs and perturbation of multiple signaling and
      metabolic determinants.
AB  - BACKGROUND: Urinary bladder cancer is one of the most fatal and expensive
      diseases of industrialized world. Despite the strenuous efforts, no seminal
      advances have been achieved for its clinical management. Given the importance of
      metabolic reprogramming in cancer cell survival and growth, we have herein
      employed 3-BrPA, a halogenated derivative of pyruvate and historically considered
      inhibitor of glycolysis, to eliminate bladder cancer cells with highly oncogenic
      molecular signatures. METHODS: Bladder cancer cells were exposed to 3-BrPA in the
      absence or presence of several specific inhibitors. Cell viability was determined
      by MTT and flow-cytometry assays; cell death, signaling activity and metabolic
      integrity by Western blotting and immunofluorescence; mutant-gene profiling by
      DNA sequencing; and gene expression by RT-sqPCR. RESULTS: 3-BrPA could activate
      dose-dependent apoptosis (type 1 PCD) and regulated necrosis (type 3 PCD) of T24
      (grade III; H-Ras(G12V); p53(DeltaY126)), but not RT4 (grade I), cells, with
      PARP, MLKL, Drp1 and Nec-7-targeted components critically orchestrating necrotic
      death. However, similarly to RIPK1 and CypD, p53 presented with non-essential
      contribution to 3-BrPA-induced cellular collapse, while reactivation of mutant
      p53 with PRIMA-1 resulted in strong synergism of the two agents. Given the
      reduced expression of MPC components (likely imposing mitochondrial dysfunction)
      in T24 cells, the suppression of constitutive autophagy (required by cells
      carrying oncogenic Ras; also, type 2 PCD) and derangement of glucose-homeostasis
      determinants by 3-BrPA critically contribute to drug-directed depletion of ATP
      cellular stores. This bioenergetic crisis is translated to severe dysregulation
      of Akt/FoxO/GSK-3, mTOR/S6, AMPK and MAPK (p44/42, p38 and SAPK/JNK) signaling
      pathways in 3-BrPA-treated T24 cells. Sensitivity to 3-BrPA (and tolerance to
      glucose deprivation) does not rely on B-Raf(V600E) or K-Ras(G13D) mutant
      oncogenic proteins, but partly depends on aberrant signaling activities of Akt,
      MAPK and AMPK kinases. Interestingly, MCT1- and macropinocytosis-mediated influx
      of 3-BrPA in T24 represents the principal mechanism that regulates cellular
      responsiveness to the drug. Besides its capacity to affect transcription in gene
      dependent manner, 3-BrPA can also induce GLUT4-specific splicing silencing in
      both sensitive and resistant cells, thus dictating alternative routes of drug
      trafficking. CONCLUSIONS: Altogether, it seems that 3-BrPA represents a promising
      agent for bladder cancer targeted therapy.

PMID- 26198752
TI  - A tunable sub-100 nm silicon nanopore array with an AAO membrane mask: reducing
      unwanted surface etching by introducing a PMMA interlayer.
AB  - Highly ordered silicon (Si) nanopores with a tunable sub-100 nm diameter were
      fabricated by a CF4 plasma etching process using an anodic aluminum oxide (AAO)
      membrane as an etching mask. To enhance the conformal contact of the AAO membrane
      mask to the underlying Si substrate, poly(methyl methacrylate) (PMMA) was spin
      coated on top of the Si substrate prior to the transfer of the AAO membrane. The
      AAO membrane mask was fabricated by two-step anodization and subsequent removal
      of the aluminum support and the barrier layer, which was then transferred to the
      PMMA-coated Si substrate. Contact printing was performed on the sample with a
      pressure of 50 psi and a temperature of 120  degrees C to make a conformal
      contact of the AAO membrane mask to the Si substrate. The CF4 plasma etching was
      conducted to transfer nanopores onto the Si substrate through the PMMA
      interlayer. The introduced PMMA interlayer prevented unwanted surface etching of
      the Si substrate by eliminating the etching ions and radicals bouncing at the gap
      between the mask and the substrate, resulting in a smooth Si nanopore array. 

PMID- 26198753
TI  - Commentary: Breaking down the barriers to using dietary therapy for refractory
      epilepsy.

PMID- 26198754
TI  - Epistylis portoalegrensis n. sp. (Ciliophora, Peritrichia): A New Freshwater
      Ciliate Species from Southern Brazil.
AB  - The peritrich ciliate Epistylis portoalegrensis n. sp. was found in two bodies of
      freshwater located in Porto Alegre, Southern Brazil. Morphological features were
      investigated using live and protargol-stained specimens. The zooids presented a
      vase to cylindrical shape narrowed at the scopula, and a mean size of 131 * 37
      MUm in vivo. A C-shaped macronucleus lay in the middle of the cell close to a
      single contractile vacuole. The oral infraciliature was typical for the genus,
      with all infundibular polykineties composed by three distinct rows of
      kinetosomes. Colonies are often nonbranched with no lateral stalk, carrying
      several zooids stemming from a single point. Specimens from the two sampling
      sites showed identical arrangement of the infraciliature, similar morphometry,
      identical 18S rDNA sequences, and a single nucleotide difference across the more
      variable ITS regions. Molecular phylogenetic analyses placed E. portoalegrensis
      in a well-supported clade containing other Epistylis species, within the order
      Vorticellida.

PMID- 26198755
TI  - Azide addition to Sc2@C66: favorable activity on unsaturated linear triquinanes
      and dramatic reactivity difference compared with the free C66 cage.
AB  - Density functional theory calculations on methyl azide additions to C66 and
      Sc2@C2v(4059)-C66 suggest that the best addition sites type E[5,6]-56 bond e2 and
      the new type D[5,6]-55 bond d for C66 and type G[5,5]-66 bond g for Sc2@C66 are
      located on the unsaturated linear triquinane moieties. 

PMID- 26198756
TI  - How to Prove that Good Learning Outcomes in Childhood Is an Independent Factor
      Strengthening the Cognitive Reserve.

PMID- 26198757
TI  - Effects of long-term entecavir treatment on the incidence of hepatocellular
      carcinoma in chronic hepatitis B patients.
AB  - BACKGROUND AND AIM: Entecavir is one of the most-used nucleoside analogues for
      the treatment of patients with chronic hepatitis B virus (HBV) infection. The aim
      of this study was to clarify the effects of long-term entecavir treatment on the
      incidence of hepatocellular carcinoma (HCC). METHODS: The participants were 249
      patients with chronic HBV infection who had been treated by entecavir for more
      than 2 years. Hepatic functional reserve and incidence of HCC were evaluated, and
      the factors that might contribute to the development of HCC were analyzed.
      RESULTS: Prothrombin activity was significantly elevated at 60 months after
      starting entecavir (from 85.9 +/- 17.4 to 97.0 +/- 16.9%, p < 0.001). The albumin
      level was also significantly elevated at 60 months after starting entecavir (from
      4.0 +/- 0.5 to 4.3 +/- 0.3 mg/dL, p < 0.001). The annual incidence of HCC
      decreased over time, and the incidence of HCC was only 1.8% at 5 years after
      starting entecavir. On multivariate analysis for HCC incidence, older age and low
      platelet count were significant, independent contributing factors. CONCLUSIONS:
      Long-term treatment with entecavir improved hepatic functional reserve and
      decreased the incidence of HCC over time after 3 years. To decrease the incidence
      of HCC, careful induction of long-term entecavir treatment in younger patients
      with chronic HBV infection and better hepatic functional reserve would be
      important.

PMID- 26198758
TI  - Effect of metformin treatment on circulating osteoprotegerin in patients with
      nonalcoholic fatty liver disease.
AB  - PURPOSE/INTRODUCTION: Growing evidence suggests complex interplay between
      nonalcoholic fatty liver disease (NAFLD) and bone health. The present study's aim
      was to examine the impact of metformin treatment on circulating osteoprotegerin
      (OPG) in patients with NAFLD, a population in which this relationship has not yet
      been studied. METHODS: In a randomized, placebo-controlled study, 63 patients
      with NAFLD were assigned to one of two groups: Group 1 received daily metformin;
      Group 2 received a placebo. Metabolic parameters, insulin resistance markers and
      OPG levels were examined at baseline and at the end of the study. RESULTS: In the
      placebo group, liver function and OPG levels did not change during the study.
      Among metformin-treated patients, significant declines in OPG and alkaline
      phosphatase were observed. CRP and ALT decreased marginally during the 4-month
      treatment period. While at baseline circulating OPG levels did not differ
      significantly between the groups, by the end of the study OPG was significantly
      lower in patients treated with metformin than in the placebo group (p < 0.0001).
      Delta OPG was significantly greater in the metformin group than the placebo group
      (p = 0.001). In the general linear model, metformin treatment was the only
      significant independent predictor of endpoint and delta OPG. CONCLUSIONS:
      Metformin treatment was associated with a significant decrease in OPG levels in
      patients with NAFLD. The effect on OPG was associated with exposure to metformin
      per se. CLINICAL TRIAL REGISTRATION NUMBER: NCT01084486.

PMID- 26198759
TI  - [Massive hemoperitoneum secondary to intraabdominal varicose veins].

PMID- 26198760
TI  - Genetic analysis and molecular mapping of QTLs for resistance to rice black
      streaked dwarf disease in rice.
AB  - Rice black-streaked dwarf disease, caused by rice black-streaked dwarf virus
      (RBSDV), is transmitted by small brown planthoppers (Laodelphax striatellus
      Fallen, SBPH) and causes severe yield loss in epidemic years in China and other
      East Asian countries. Breeding for resistance to RBSDV is a promising strategy to
      control the disease. We identified Tetep that showed resistance to RBSDV using a
      field test and artificial inoculation test. An evaluation of the resistance
      mechanism revealed that Tetep was resistant to RBSDV but not to SBPH. Genetic
      analysis showed that the resistance of Tetep to RBSDV was controlled by
      quantitative trait loci (QTLs). Three new QTLs for RBSDV resistance were
      identified in this study, i.e., qRBSDV-3, qRBSDV-10 and qRBSDV-11. The LOD scores
      of qRBSDV-3, qRBSDV-10 and qRBSDV-11 were 4.07, 2.24 and 2.21, accounting for
      17.5%, 0.3% and 12.4% of the total phenotypic variation, respectively. All the
      resistance loci identified in this study were associated with virus resistance
      genes. The alleles for enhancing resistance on chromosomes 3 and 11 originated
      from Tetep, whereas the other allele on chromosome 10 originated from a
      susceptible parent. The identified new resistance QTLs in this study are useful
      resources for efficiently breeding resistant rice cultivars to RBSDV. 

PMID- 26198761
TI  - High-Efficiency All-Solution-Processed Light-Emitting Diodes Based on Anisotropic
      Colloidal Heterostructures with Polar Polymer Injecting Layers.
AB  - Colloidal quantum dots (QDs) are emerging as true candidates for light-emitting
      diodes with ultrasaturated colors. Here, we combine CdSe/CdS dot-in-rod
      heterostructures and polar/polyelectrolytic conjugated polymers to demonstrate
      the first example of fully solution-based quantum dot light-emitting diodes (QD
      LEDs) incorporating all-organic injection/transport layers with high brightness,
      very limited roll-off and external quantum efficiency as high as 6.1%, which is
      20 times higher than the record QD-LEDs with all-solution-processed organic
      interlayers and exceeds by over 200% QD-LEDs embedding vacuum-deposited organic
      molecules. 

PMID- 26198762
TI  - Altered cortical hubs in functional brain networks in amyotrophic lateral
      sclerosis.
AB  - Cortical hubs are highly connected nodes in functional brain networks that play
      vital roles in the efficient transfer of information across brain regions.
      Although altered functional connectivity has been found in amyotrophic lateral
      sclerosis (ALS), the changing pattern in functional network hubs in ALS remains
      unknown. In this study, we applied a voxel-wise method to investigate the
      changing pattern of cortical hubs in ALS. Through resting-state fMRI, we
      constructed whole-brain voxel-wise functional networks by measuring the temporal
      correlations of each pair of brain voxels and identified hubs using the graph
      theory method. Specifically, a functional connectivity strength (FCS) map was
      derived from the data on 20 patients with ALS and 20 healthy controls. The brain
      regions with high FCS values were regarded as functional network hubs. Functional
      hubs were found mainly in the bilateral precuneus, parietal cortex, medial
      prefrontal cortex, and in several visual regions and temporal areas in both
      groups. Within the hub regions, the ALS patients exhibited higher FCS in the
      prefrontal cortex compared with the healthy controls. The FCS value in the
      significantly abnormal hub regions was correlated with clinical variables.
      Results indicated the presence of altered cortical hubs in the ALS patients and
      could therefore shed light on the pathophysiology mechanisms underlying ALS. 

PMID- 26198763
TI  - Independent effect of fatigue on health-related quality of life in patients with
      idiopathic Parkinson's disease.
AB  - Nonmotor symptoms (NMS) of idiopathic Parkinson's disease (IPD), specifically
      fatigue, depression and sleep disturbances, are important contributors for worse
      quality of life and poor patient outcomes. The aim of this research is to
      determine the relationship between fatigue and other NMS and the independent
      effect of fatigue on health-related quality of life (HRQoL) in patients with IPD.
      86 IPD patients and 85 healthy individuals were included in our study.
      Participants were evaluated by their answers to the Beck Depression Inventory,
      Fatigue Severity Scale, Epworth Sleepiness Scale and Parkinson's Disease
      Questionnaire-39. Hoehn-Yahr stage, disease duration, medications and
      demographical characteristics were also noted. ROC analysis was used to determine
      the cutoff point for HRQoL. Nonparametric Spearman correlation analysis was used
      for determining the relationship between variables. Independent factors which
      affect HRQoL were detected by multiple forward stepwise logistic regression
      analysis. NMS were associated with each other and with HRQoL when they act
      concomitantly (p < 0.001). Of these three frequent NMS, depression (p < 0.05) and
      fatigue (p < 0.001) had independent worsening effect on HRQoL, whereas sleep
      disturbances did not (p > 0.05). The stage of IPD and levodopa-entacapone
      treatment had independent effects on HRQoL too (p < 0.05). Fatigue was found as
      the most important factor which affects HRQoL among all investigated NMS. So, it
      is important to ask about fatigue in routine controls of IPD patients and try to
      treat it for improving life quality.

PMID- 26198764
TI  - Genome-wide association study of schizophrenia in Ashkenazi Jews.
AB  - Schizophrenia is a common, clinically heterogeneous disorder associated with
      lifelong morbidity and early mortality. Several genetic variants associated with
      schizophrenia have been identified, but the majority of the heritability remains
      unknown. In this study, we report on a case-control sample of Ashkenazi Jews
      (AJ), a founder population that may provide additional insights into genetic
      etiology of schizophrenia. We performed a genome-wide association analysis (GWAS)
      of 592 cases and 505 controls of AJ ancestry ascertained in the US. Subsequently,
      we performed a meta-analysis with an Israeli AJ sample of 913 cases and 1640
      controls, followed by a meta-analysis and polygenic risk scoring using summary
      results from Psychiatric GWAS Consortium 2 schizophrenia study. The U.S. AJ
      sample showed strong evidence of polygenic inheritance (pseudo-R(2) ~9.7%) and a
      SNP-heritability estimate of 0.39 (P = 0.00046). We found no genome-wide
      significant associations in the U.S. sample or in the combined US/Israeli AJ meta
      analysis of 1505 cases and 2145 controls. The strongest AJ specific associations
      (P-values in 10(-6) -10(-7) range) were in the 22q 11.2 deletion region and
      included the genes TBX1, GLN1, and COMT. Supportive evidence (meta P < 1 * 10(-4)
      ) was also found for several previously identified genome-wide significant
      findings, including the HLA region, CNTN4, IMMP2L, and GRIN2A. The meta-analysis
      of the U.S. sample with the PGC2 results provided initial genome-wide significant
      evidence for six new loci. Among the novel potential susceptibility genes is
      PEPD, a gene involved in proline metabolism, which is associated with a Mendelian
      disorder characterized by developmental delay and cognitive deficits.

PMID- 26198765
TI  - Restrictive versus liberal transfusion strategy for red blood cell transfusion in
      critically ill patients and in patients with acute coronary syndrome: a
      systematic review, meta-analysis and trial sequential analysis.
AB  - INTRODUCTION: The risks and benefits of transfusing critically ill patients
      continue to evoke controversy. Specifically, the critically ill patients with
      active ischemic cardiac disease continue to represent a "gray area" in the
      literature. EVIDENCE ACQUISITION: Meta-analysis of the effects of lower versus
      higher hemoglobin thresholds on mortality in critically ill patients was carried
      out using PRISMA methodology. A systematic research was performed in PubMed,
      Embase, and the Cochrane Library (last update, December 2014). INCLUSION
      CRITERIA: Anemic critically ill adult patients admitted to intensive care units
      and/or anemic patients with acute coronary syndrome in which a restrictive vs.
      liberal transfusion therapy was compared. PRIMARY ENDPOINT: mortality. Included
      studies were subjected to quantifiable analysis, predefined subgroup analysis,
      trial sequential analysis and predefined sensitivity analysis. EVIDENCE
      SYNTHESIS: Thirty RCT's were initially identified; 6 fulfilled the inclusion
      criteria, including 2156. There were no differences in mortality between the
      restrictive and liberal groups (RR: 0.86, 95% CI 0.70-1.05 P=0.14), neither in
      patients with chronic cardiovascular disease subgroup (RR: 1.13, 95% IC 0.88-1.46
      P=0.34). However, there is a trend towards decreased mortality in the subgroup
      critically ill (RR: 0.86, 95% CI 0.73-1.01 P=0.06); while in the subgroup of
      patients with acute myocardial infarct seems like it might be a non-significant
      trend towards increased mortality (RR: 3.85, 95% CI 0.82-18.0 P=0.09).
      CONCLUSIONS: Restrictive strategy is at least as effective to liberal strategy in
      critically ill patients. Nevertheless, there is insufficient evidence to
      recommend a restrictive strategy for patients with acute coronary syndrome.

PMID- 26198766
TI  - Desflurane and sevoflurane use during low- and minimal-flow anesthesia at fixed
      vaporizer settings.
AB  - BACKGROUND: The pharmacokinetics for sevoflurane and desflurane makes them
      suitable for low-flow anesthesia. The aim of the present study was to assess the
      use of desflurane and sevoflurane at constant vaporizer settings and fixed low
      fresh gas flows. METHODS: One hundred ASA 1-2 patients undergoing elective
      laparoscopic surgery were randomized into 4 groups (25 patients each): a fixed
      fresh gas flow 1.0 or 0.5 L/min with desflurane (D1.0 and D0.5) or sevoflurane
      (S1.0 and S0.5) throughout anesthesia. A fixed vaporizer setting, sevoflurane 6%
      and desflurane 18% was used during wash-in. Time to reach 1 and 1.5 minimum
      alveolar concentration (MAC), emergence and gas consumption from start to end of
      surgery was studied. RESULTS: Time to reach 1 MAC age adjusted desflurane or
      sevoflurane was D0.5 8.5+/-1.7, D1.0 3.7+/-0.7, S0.5 15.2+/-2.4 and S1.0 6.2+/
      1.3 minutes, respectively (P<0.001), and times to increase from 1 to 1.5 MAC
      differed also significantly. Desflurane anesthesia was associated to
      significantly shorter time to extubation 6.7+/-2.3 vs. 10+/-2.3 minutes for
      sevoflurane (P<0.001). The amount of agent consumed g/min. was significantly
      reduced for both 0.5 L/min groups: 30% less for desflurane and 19% for
      sevoflurane. CONCLUSIONS: We found an almost twice as rapid wash-in with
      desflurane and expectedly faster emergence. Gas consumption was lower at 0.5
      L/min than it was at 1 L/min for both gases studied however most pronounced for
      desflurane. Desflurane has clear advantages for minimal fresh gas flow
      anesthesia.

PMID- 26198767
TI  - Should the anesthesiologist's role as "warrantor" of patients' health undergo
      Courts' judgements?

PMID- 26198768
TI  - Ehlers-Danlos Syndrome: Arthroscopic Management for Extreme Soft-Tissue Hip
      Instability.
AB  - PURPOSE: To present outcomes in a series of patients with Ehlers-Danlos syndrome
      (EDS)-hypermobility type who underwent hip arthroscopy for associated hip pain
      and extreme capsular laxity. METHODS: A retrospective chart review identified 16
      hips with confirmed EDS--hypermobility type that underwent hip arthroscopy for
      continued pain and capsular laxity. All patients had complaints of "giving way"
      and pain, an easily distractible hip with manual traction under fluoroscopy, and
      a patulous capsule at the time of surgery. No patient had osseous evidence of
      acetabular hip dysplasia or prior confirmed hip dislocation. Outcomes were
      evaluated preoperatively and postoperatively with the modified Harris Hip Score
      (mHHS), the 12-Item Short Form Health Survey (SF-12), and a visual analog scale
      (VAS) for pain. RESULTS: Evidence of symptomatic femoroacetabular impingement
      (FAI) was found in 15 hips (93.8%). The 16th hip had subjective giving way with a
      positive anterior impingement test and was easily distractible, had a labral
      tear, and had a patulous capsule at the time of surgery. The mean follow-up
      period was 44.61 months (range, 12 to 99 months). The mean preoperative lateral
      center-edge angle was 31.8 degrees  (range, 25 degrees  to 44 degrees ), and the
      mean Tonnis angle was 3.6 degrees  (range, -2 degrees  to 8 degrees ). Mean
      femoral version measured on computed tomography (CT) scans was 19.2 degrees 
      (range, -4.0 degrees  to 31.0 degrees ). Of the hips, 13 underwent primary
      arthroscopy and 3 underwent revision. All hips underwent hip arthroscopy with an
      interportal capsular cut only and arthroscopic capsular plication. There were 13
      labral repairs, 2 labral debridements, 8 rim resections, 15 femoral resections, 2
      psoas tenotomies, and 1 microfracture. Improved stability with an inability to
      distract the hip with manual traction under fluoroscopy was noted in all hips
      after plication. The mean alpha angle preoperatively was 58.7 degrees  on
      anteroposterior radiographs and 63.6 degrees  on lateral radiographs compared
      with 47.4 degrees  and 46.1 degrees , respectively, postoperatively. There were
      significant improvements for all outcomes (mHHS, P = .002; SF-12 score, P = .027;
      and VAS score, P = .0004). The mean mHHS, SF-12 score, and VAS score were 45.6
      points, 62.4 points, and 6.5 points, respectively, preoperatively compared with
      88.5 points, 79.3 points, and 1.6 points, respectively, at a mean follow-up of 45
      months. No EDS patients were lost to follow-up or excluded from analysis. The
      mean improvement in mHHS from preoperatively to postoperatively was 42.9 points,
      and there were no iatrogenic dislocations. One patient underwent further revision
      arthroscopy for recurrent pain, subjective giving way, and capsular laxity.
      CONCLUSIONS: FAI and extreme capsular laxity can be seen in the setting of EDS.
      Although increased femoral version was common, acetabular dysplasia was not
      common in our study. Meticulous capsular plication, arthroscopic correction of
      FAI when present, and labral preservation led to dramatic improvements in
      outcomes and subjective stability without any iatrogenic dislocations in this
      potentially challenging patient population. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 26198769
TI  - Cardiotrophin-like cytokine factor 1 (CLCF1) and neuropoietin (NP) signalling and
      their roles in development, adulthood, cancer and degenerative disorders.
AB  - Mutations in cardiotrophin-like cytokine factor (CLCF1) and the related cytokine
      to which it binds, cytokine receptor-like factor 1 (CRLF1), are associated with
      Crisponi/cold induced sweating syndromes, and lead to early neonatal death in
      mice due to a suckling defect. These cytokines are members of the IL-6
      superfamily, and form a range of composite cytokines that signal through gp130
      bound either to the ciliary neurotrophic factor receptor (CNTFR) or a complex
      that involves the IL-27 p28 subunit. This review describes current knowledge of
      the signalling complexes formed by these cytokines, and explores their described
      and suggested roles in the neural, haematopoietic, skeletal, renal, immune and
      respiratory systems during development and adulthood, and in degenerative
      diseases and cancer. 

PMID- 26198770
TI  - Oncostatin M and interleukin-31: Cytokines, receptors, signal transduction and
      physiology.
AB  - Oncostatin M (OSM) and interleukin-31 (IL-31) are two cytokines belonging to the
      IL-6 family which share a common signaling receptor subunit, the OSM receptor
      beta (OSMRbeta). Both of them are released by monocytes/macrophages, dendritic
      cells and T lymphocytes in inflammatory situations and upon binding to their
      respective receptor complexes they signal mainly via the JAK/STAT pathway.
      Besides sharing many biochemical properties, both display divergent physiological
      functions. This review summarizes aspects of cytokine transcription and
      biosynthesis, cytokine-receptor interactions, cross-species activities, signal
      transduction and physiology delineated from recent findings in genetic mouse
      models for both cytokines, OSM and IL-31. 

PMID- 26198772
TI  - The consumers' social media use in choosing physicians and hospitals: the case
      study of the province of Izmir.
AB  - Manifested as a reflection of the Internet technology progress, web 2.0 has
      transformed communication among people to different dimensions while increasing
      the social use of Internet. Thus, the concept of social media has entered our
      lives. Blogs, forums, Facebook, Twitter and YouTube applications are but few of
      the social media platforms with active users exceeding millions. As in many other
      subjects, these and others are also environments where people share information
      and their positive or negative experiential views with respect to healthcare
      issues and services. Hence, the social media communication and exchange of
      information are deemed influential on the process of receiving health services.
      In the present study that aims to determine social media use of individuals in
      their choice of physicians, dentists and hospitals, a survey, as a data
      collection instrument, has been carried out to 947 residents of the province of
      Izmir. Individuals participating in the study have stated that they have used
      social media in choosing a physician (41.9% of the participants), dentist (34.1%
      of the participants) and hospitals (41.7% of the participants). The study has
      revealed that individuals are affected by social media in their healthcare
      choices. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26198771
TI  - The Global Influenza Hospital Surveillance Network (GIHSN): a new platform to
      describe the epidemiology of severe influenza.
AB  - BACKGROUND: Influenza is a global public health problem. However, severe
      influenza only recently has been addressed in routine surveillance. OBJECTIVES:
      The Global Influenza Hospital Surveillance Network (GIHSN) was established to
      study the epidemiology of severe influenza in consecutive seasons in different
      countries. Our objective is to describe the GIHSN approach and methods. METHODS:
      The GIHSN uses prospective active surveillance to identify consecutive influenza
      admissions in permanent residents of well-defined geographic areas in sites
      around the world. A core common protocol is followed. After consent, data are
      collected on patient characteristics and clinical outcomes, respiratory swabs are
      obtained, and the presence of influenza virus and subtype or lineage is
      ascertained by polymerase chain reaction. Data are collated and analyzed at the
      GIHSN coordination center. RESULTS: The GIHSN has run its activities for two
      consecutive influenza seasons, 2012-2013 and 2013-2014, and hospitals in Brazil,
      China, France, Russian Federation, Turkey, and Spain have been involved in one or
      both seasons. Consistency on the application of the protocol and heterogeneity
      for the first season have been addressed in two previous publications. During
      both seasons, 19 677 eligible admissions were recorded; 11 843 (60%) were
      included and tested, and 2713 (23%) were positive for influenza: 991 (37%)
      A(H1N1); 807 (30%) A(H3N2); 583 (21%) B/Yamagata; 56 (2%) B/Victoria and 151 (6%)
      influenza A; and 125 (5%) influenza B were not characterized. CONCLUSIONS: The
      GIHSN is a platform that provides information on severe influenza worldwide,
      applying a common core protocol and a consistent case definition.

PMID- 26198773
TI  - Recent advances in flexible perovskite solar cells.
AB  - Flexible and low-weight thin-film perovskite solar cells have attracted
      considerable attention for developing large-area, roll-to-roll and differently
      shaped photovoltaics with improved power conversion efficiencies. In this review,
      we describe how researchers have adopted different approaches to enhance the
      device performance of the flexible perovskite solar cells to compete with rigid
      substrates with tailored electron/hole transport materials and flexible
      substrates. 

PMID- 26198774
TI  - Urbanisation and geographic variation of overweight and obesity in India: a cross
      sectional analysis of the Indian Demographic Health Survey 2005-2006.
AB  - OBJECTIVES: We examined the nationwide geographic variation of overweight and
      obesity in India, as well as a range of potential correlates of excess body fat.
      METHODS: We conducted cross-sectional analyses of the 2005-2006 Indian
      Demographic Health Survey (IDHS), based on 161,050 individuals (age range 18-54
      years). Multivariate logistic regression models were used to determine odds
      ratios (OR) of overweight and obesity compared to normal weight with associated
      correlates. RESULTS: The overall prevalence was 12.4% for overweight, 3.2% for
      obesity, and 26.5% for underweight. After multivariate adjustment, obesity was
      nearly thrice more likely in urban areas than in rural (OR 2.73, 95% CI 2.53
      2.94). Women were 2.71 times more likely to be obese than men (95% CI 2.50-2.95).
      Better socioeconomic status was significantly associated with overweight and
      obesity. Overweight (OR 1.38, 95% CI 1.31-1.47) and obesity (OR 1.46, 95% CI 1.32
      1.61) were most likely to occur in India's Southern zone, when controlled for
      confounding factors. CONCLUSIONS: High-risk estimates for overweight/obesity in
      urban settings, along with socioeconomic prowess in India and the resulting
      nutritional transition make a compelling case for public health policy on healthy
      lifestyles to avert the growing burden of non-communicable diseases associated
      with overweight/obesity.

PMID- 26198775
TI  - Very long haplotype tracts characterized at high resolution from HLA homozygous
      cell lines.
AB  - The HLA region of chromosome 6 contains the most polymorphic genes in humans.
      Spanning ~5 Mbp the densely packed region encompasses approximately 175 expressed
      genes including the highly polymorphic HLA class I and II loci. Most of the other
      genes and functional elements are also polymorphic, and many of them are directly
      implicated in immune function or immune-related disease. For these reasons, this
      complex genomic region is subject to intense scrutiny by researchers with the
      common goal of aiding further understanding and diagnoses of multiple immune
      related diseases and syndromes. To aid assay development and characterization of
      the classical loci, a panel of cell lines partially or fully homozygous for HLA
      class I and II was assembled over time by the International Histocompatibility
      Working Group (IHWG). Containing a minimum of 88 unique HLA haplotypes, we show
      that this panel represents a significant proportion of European HLA allelic and
      haplotype diversity (60-95 %). Using a high-density whole genome array that
      includes 13,331 HLA region SNPs, we analyzed 99 IHWG cells to map the coordinates
      of the homozygous tracts at a fine scale. The mean homozygous tract length within
      chromosome 6 from these individuals is 21 Mbp. Within HLA, the mean haplotype
      length is 4.3 Mbp, and 65 % of the cell lines were shown to be homozygous
      throughout the entire region. In addition, four cell lines are homozygous
      throughout the complex KIR region of chromosome 19 (~250 kbp). The data we
      describe will provide a valuable resource for characterizing haplotypes,
      designing and refining imputation algorithms and developing assay controls. 

PMID- 26198776
TI  - Procedure for preventing response strain on random interval schedules with a
      linear feedback loop.
AB  - An experiment examined the impact of a procedure designed to prevent response or
      extinction strain occurring on random interval schedules with a linear feedback
      loop (i.e., an RI+ schedule). Rats lever-pressed for food reinforcement on either
      a RI+ or a random interval (RI) schedule that was matched to the RI+ schedule in
      terms of reinforcement rate. Two groups of rats responded on an RI+ and two on an
      RI schedule matched for rate of reinforcement. One group on each schedule also
      received response-independent food if there had been no response for 60 s, and
      response-independent food continued to be delivered on an RT-60 schedule until a
      response was made. Rats on the RI and RI+ obtained similar rates of reinforcement
      and had similar reinforced inter-response times to one another. On the schedules
      without response-independent food, rats had similar rates of response to one
      another. However, while the delivery of response-independent food reduced rates
      of response on an RI schedule, they enhanced response rates on an RI+ schedule.
      These results suggest that rats can display sensitivity to the molar aspects of
      the free-operant contingency, when procedures are implemented to reduce the
      impact of factors such as extinction-strain. 

PMID- 26198777
TI  - A cyclically actuated electrolytic drug delivery device.
AB  - This work, focusing on an implantable drug delivery system, presents the first
      prototype electrolytic pump that combines a catalytic reformer and a cyclically
      actuated mode. These features improve the release performance and extend the
      lifetime of the device. Using our platinum (Pt)-coated carbon fiber mesh that
      acts as a catalytic reforming element, the cyclical mode is improved because the
      faster recombination rate allows for a shorter cycling time for drug delivery.
      Another feature of our device is that it uses a solid-drug-in-reservoir (SDR)
      approach, which allows small amounts of a solid drug to be dissolved in human
      fluid, forming a reproducible drug solution for long-term therapies. We have
      conducted proof-of-principle drug delivery studies using such an electrolytic
      pump and solvent blue 38 as the drug substitute. These tests demonstrate power
      controlled and pulsatile release profiles of the chemical substance, as well as
      the feasibility of this device. A drug delivery rate of 11.44 +/- 0.56 MUg min(
      1) was achieved by using an input power of 4 mW for multiple pulses, which
      indicates the stability of our system. 

PMID- 26198778
TI  - (99m)Tc-human serum albumin nanocolloids: particle sizing and radioactivity
      distribution.
AB  - Several parameters affect the biodistribution of administered nanocolloids (NC)
      for Sentinel Lymph Node (SLN) detection: particle size distribution, number of Tc
      atoms per particle and specific activity (SA). Relatively few data are available
      with frequently conflicting results. (99m)Tc-NC-human serum albumin (HSA)
      Nanocoll(r), Nanoalbumon(r) and Nanotop(r) were analysed for particles'
      dimensional and radioactivity distribution, and a mathematical model was
      elaborated to estimate the number of particles involved. Commercially available
      kits were reconstituted at maximal SA of 11 MBq/ug HSA. Particles size
      distribution was evaluated by Dynamic Light Scattering. These data were related
      to the radioactivity distribution analysis passing labelled NC through three
      polycarbonate filters (15-30-50-nm pore size) under vacuum. Highest radioactivity
      was carried by 30-50 nm particles. The smallest ones, even though most numerous,
      carried only the 10% of (99m)Tc atoms. Nanocoll and Nanotop are not significantly
      different, while Nanoalbumon is characterized by largest particles (>30 nm) that
      carried the most of radioactivity (80%). Smallest particles could saturate the
      clearing capacity of macrophages; therefore, if the tracer is used for SLN
      detection, more node tiers could be visualized, reducing accuracy of SLN mapping.
      Manufacturers could implement technical leaflets with particle size distribution
      and could improve the labelling protocol to provide clinicians useful
      information.

PMID- 26198779
TI  - Vascular graft employment in the surgical treatment of acute and chronic acromio
      clavicular dislocation.
AB  - OBJECTIVES: To show the efficiency and safety of a surgical treatment in both
      acute and chronic acromio-clavicular junction (ACJ) dislocations. DESIGN:
      Retrospective. SETTING: Department of Orthopedics and Traumatology at IRCCS San
      Raffaele Hospital. PATIENTS/PARTICIPANTS: This study was performed on 37 subjects
      classified as Rockwood grade III-V or Tossy III ACJ dislocation. PROCEDURE: The
      surgical treatment was carried out by placing a vascular graft
      (GorePropaten((r))) between the tip of the coracoid process and the mid-lateral
      side of the clavicle with two temporary percutaneous K-wires positioned in a
      parallel manner in the AC ligament through the acromion and clavicle for 30 days
      to improve stability. MAIN OUTCOME MEASUREMENTS: Outcomes were assessed using the
      Constant Shoulder (CS) score, DASH score, subjective satisfaction, and stability
      of AC joint at 24 months. UCLA scores taken preoperatively and at 15-month follow
      up were used to perform statistical analysis significance using a control group
      treated conservatively. Postoperative X-rays were examined to assess joint
      stability after 24 months. RESULTS: Preoperative CS score was 51 +/- 12 in the
      acute group and 55 +/- 15 in the chronic group. Follow-up mean CS score was 88 +/
      11 in the acute group and 82 +/- 20 in the chronic group at 24 months.
      Preoperative DASH score was 19 +/- 3 in the acute group and 14 +/- 5 in the
      chronic group. Mean DASH score was 3.60 +/- 7 in the acute group and 6.42 +/- 6
      in the chronic group. Preoperative UCLA scores were 14.6 +/- 2 and 15 +/- 7 in
      the acute group and chronic group, respectively. At 15-month follow-up, UCLA
      scores of 28.1 +/- 1.9 and 27.7 +/- 1 in the acute and chronic group,
      respectively, showed a significant improvement (p < 0.05) compared with UCLA
      scores taken preoperatively and at 15 months in the control group treated
      conservatively of 15.8 +/- 0.9 and 16.2 +/- 0.9, respectively. Results were good
      to excellent in 10 patients from the acute group and 23 patients from the chronic
      group who presented clinical stability of the AC joint without pain.
      Postoperative radiography showed anatomical repositioning of the ACJ and joint
      stability in 35 cases, but only two patients showed a partial re-dislocation at
      the 24-month X-ray follow-up. No infections, either deep or superficial, or nerve
      palsies were reported. CONCLUSIONS: Given the results obtained during the study
      and the response of the patients in both acute and chronic groups, the authors
      found that the employment of a vascular graft combined with temporary
      percutaneous K-wires is able to improve the patient's clinical outcome following
      an acromio-clavicular joint dislocation.

PMID- 26198780
TI  - Medial malleolus screws: out in one view and out.
AB  - Cartilage damage or mechanical blocking from screw penetration into intra
      articular cartilage can reduce the chances of successful outcomes during medial
      malleolus fixation. There have been diverging opinions among surgeons concerning
      the reliability of radiographic assessment of fracture fixation and malleolus
      screw positioning. Therefore, this radiographic study examines the location of
      medial malleolus lag screws relative to the ankle mortise articular surface. In
      three Sawbones models, Kirschner wires were overdrilled with a 4.0-mm cannulated
      cortical screw simulating screws that would be intra- and extra-articular when
      performing open reduction and internal fixation of a medial malleolar fracture.
      Under fluoroscopy, images were evaluated to determine whether known intra
      articular screws appeared extra-articular in any radiographic view. No image from
      models with known intra-articular penetration appeared extra-articular in any
      view or under "live" fluoroscopy. At 20 degrees  internal rotation, a screw with
      a known extra-articular position appeared to be within the cartilage. Intra
      operative fluoroscopy is necessary to ensure proper extra-articular placement of
      screws. If a screw is pictured extra-articular in any radiograph, then it can be
      assumed that the screw is indeed out of the joint.

PMID- 26198782
TI  - Geographic differences in heart failure trials.
AB  - Randomized controlled trials (RCTs) are essential to develop advances in heart
      failure (HF). The need for increasing numbers of patients (without substantial
      cost increase) and generalization of results led to the disappearance of
      international boundaries in large RCTs. The significant geographic differences in
      patients' characteristics, outcomes, and, most importantly, treatment effect
      observed in HF trials have recently been highlighted. Whether the observed
      regional discrepancies in HF trials are due to trial-specific issues, patient
      heterogeneity, structural differences in countries, or a complex interaction
      between factors are the questions we propose to debate in this review. To do so,
      we will analyse and review data from HF trials conducted in different world
      regions, from heart failure with preserved ejection fraction (HF-PEF), heart
      failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF).
      Finally, we will suggest objective and actionable measures in order to mitigate
      regional discrepancies in future trials, particularly in HF-PEF where prognostic
      modifying treatments are urgently needed and in which trials are more prone to
      selection bias, due to a larger patient heterogeneity. 

PMID- 26198781
TI  - Genetics of resistant hypertension: a novel pharmacogenomics phenotype.
AB  - Resistant hypertension (RHTN), defined as an uncontrolled blood pressure despite
      the use of multiple antihypertensive medications, is an increasing clinical
      problem associated with increased cardiovascular (CV) risk, including stroke and
      target organ damage. Genetic variability in blood pressure (BP)-regulating genes
      and pathways may, in part, account for the variability in BP response to
      antihypertensive agents, when taken alone or in combination, and may contribute
      to the RHTN phenotype. Pharmacogenomics focuses on the identification of genetic
      factors responsible for inter-individual variability in drug response. Expanding
      pharmacogenomics research to include patients with RHTN taking multiple BP
      lowering medications may identify genetic markers associated with RHTN. To date,
      the available evidence surrounding pharmacogenomics in RHTN is limited and
      primarily focused on candidate genes. In this review, we summarize the most
      current data in RHTN pharmacogenomics and offer some recommendations on how to
      advance the field. 

PMID- 26198783
TI  - Malignant syphilis.

PMID- 26198784
TI  - Memory of an exotic holiday.

PMID- 26198785
TI  - The diagnostic usefulness of fecal lactoferrin in the assessment of Crohn's
      disease activity.
AB  - BACKGROUND: Diagnosis and monitoring of Crohn's disease (CD) is difficult and
      time-consuming. In recent years, diagnostic usefulness of fecal calprotectin has
      been proven. However, data on the utility of other fecal markers are scarce.
      AIMS: To evaluate the usefulness of fecal lactoferrin (FL) in the assessment of
      CD activity. METHODS: The group consisted of 101 CD patients (median age: 30
      years, IQR: 24-37). FL was measured in a single stool sample by using the
      immunoenzymatic methods. The clinical activity of the disease was evaluated by
      using the Crohn's Disease Activity Index (CDAI). Depending on the location of the
      disease, either a colonoscopy or magnetic resonance enterography was performed or
      both in order to evaluate the disease activity by using appropriate endoscopic
      and enterographic scores. RESULTS: Median FL concentration was 84.14 (IQR: 36.4
      302.9) MUg/ml and it correlated with C-reactive protein concentration
      (p=0.0000001, r=0.5), CDAI (p=0.002, r=0.3) and colonic Simple Endoscopic Score
      for Crohn's Disease (SES-CD) (p=0.000004, r=0.5). Assuming endoscopic remission
      in the large intestine with colonic SES-CD<=3 points, a ROC curve showed that FL
      concentration of 145.82 MUg/ml had 84.6% sensitivity and 60.5% specificity in
      discriminating CD patients with endoscopically active and inactive disease [AUC:
      0.676 (95% CI: 0.531-0.8), (p=0.0347)]. The positive predictive value for this
      concentration was 42% and negative predictive value -92%. CONCLUSIONS: FL is a
      sensitive marker of CD activity and it reliably reflects the mucosal inflammatory
      lesions in large intestine. Thus, it can be helpful in diagnostics and monitoring
      of CD.

PMID- 26198786
TI  - History of alcohol abuse after major non-cardiac surgery and postoperative
      cognitive dysfunction.
AB  - INTRODUCTION: The risk factors for postoperative cognitive dysfunction (POCD)
      after non-cardiac surgery include advanced age and preexisting cognitive
      impairment. MATERIAL AND METHODS: Data was collected in a prospective manner on
      220 patients of both genders. Patients were triaged into three groups, with
      American Society of Anesthesiologists-ASA Physical Classification System levels I
      IV. Patients were 55 years of age and older, with self-reported alcohol abuse and
      were matched to age-, sex-, and education-matched nonalcoholic controls. They
      were tested using a neurocognitive battery before and two weeks after elective
      surgery or after a corresponding time interval without surgery. Verbal memory,
      visuospatial memory, and executive functions were assessed. Neurologic
      examination was performed in order to exclude subjects with potential
      cerebrovascular damage. Standard laboratory analyses were done and findings
      recorded. Significant predisposing factors for developing POCD were noted.
      RESULTS: From the total number of participants involved in the study, 135 (67.5%)
      patients belonged to ASA class III. Among all patients, 168 (84%) patients were
      chronic alcohol users. Pearson's chi(2) test shows a statistically significant
      difference regarding the use of alcohol (chi(2)=19.220, df=1, p=0.000, p<0.05).
      Significant three-way interactions (analysis of variance) for Visual Immediate
      Recall, Visual Delayed Recall, Semantic Fluency, Phonemic Fluency, and the Color
      Word Stroop Test implied that cognitive performance in the alcoholic group
      decreased after surgery. DISCUSSION: In the study by Mason which involved 255
      elderly patients that were postoperatively admitted to the intensive care unit
      following a major abdominal surgery, development of POCD was two times greater in
      urgent cases (~40% of cases), when compared to elective interventions.
      CONCLUSION: Our results complement the data given by the World Health
      Organization and results of similar studies.

PMID- 26198787
TI  - A Multifunctional Bimetallic Molecular Device for Ultrasensitive Detection, Naked
      Eye Recognition, and Elimination of Cyanide Ions.
AB  - A new bimetallic Fe(II) -Cu(II) complex was synthesized, characterized, and
      applied as a selective and sensitive sensor for cyanide detection in water. This
      complex is the first multifunctional device that can simultaneously detect
      cyanide ions in real water samples, amplify the colorimetric signal upon
      detection for naked-eye recognition at the parts-per-million (ppb) level, and
      convert the toxic cyanide ion into the much safer cyanate ion in situ. The
      mechanism of the bimetallic complex for high-selectivity recognition and
      signaling toward cyanide ions was investigated through a series of binding
      kinetics of the complex with different analytes, including CN(-) , SO4 (2-) ,
      HCO3 (-) , HPO4 (2-) , N3 (-) , CH3 COO(-) , NCS(-) , NO3 (-) , and Cl(-) ions.
      In addition, the use of the indicator/catalyst displacement assay (ICDA) is
      demonstrated in the present system in which one metal center acts as a receptor
      and inhibitor and is bridged to another metal center that is responsible for
      signal transduction and catalysis, thus showing a versatile approach to the
      design of new multifunctional devices. 

PMID- 26198788
TI  - Off the mark: Current lung cancer screening guidelines miss those most at risk.

PMID- 26198789
TI  - ACS report: Progress lags in some cancer control efforts.

PMID- 26198793
TI  - Dendritic cell-derived exosomes carry the major cat allergen Fel d 1 and induce
      an allergic immune response.
AB  - Exosomes are nano-sized membrane vesicles (50-120 nm), which are released from a
      wide variety of cells. Depending on their cellular origin, they can induce immune
      stimulatory-, inhibitory-, or tolerance-inducing effects. However, it is still
      unclear what role exosomes play during human inflammatory diseases. It has not
      been studied whether exosomes derived from human dendritic cells (DCs), the first
      cells to encounter allergens in the mucosa, can carry aeroallergens and
      contribute to allergic immune responses. We therefore explored whether DC-derived
      exosomes can present the major cat allergen Fel d 1 and whether they thereby
      contribute to the pathogenesis of allergic disease. Our results demonstrate that
      exosomes are able to present aeroallergens and thereby induce T-cell T(H)2-like
      cytokine production in allergic donors. Thus, these exosomes may be important
      immune-stimulatory factors in allergic immune responses and important targets or
      engineered tools in immunotherapy. 

PMID- 26198794
TI  - (99m)Tc-HDP SPECT/MRI in isolated xanthoma of the temporal bone.

PMID- 26198795
TI  - Lessons learned in andrology: looking at the spermatozoa in context.

PMID- 26198796
TI  - Have rates of erectile dysfunction improved within the past 17 years after
      radical prostatectomy? A systematic analysis of the control arms of prospective
      randomized trials on penile rehabilitation.
AB  - Based on case series, potency rates after radical prostatectomy (RPE) differ
      substantially and - furthermore - it remains unclear whether they have improved
      in more recent surgical series. The purpose of this study was to investigate
      whether potency rates after RPE have improved over the years. A systematic
      analysis of the control arms of all randomized controlled trials (RCT; n = 11) on
      penile rehabilitation after RPE was carried out. In total, 2009 patients were
      included in these RCTs, 685 thereof in the respective control arms, who were
      either observed or received placebo. Assessment of erectile function in these
      studies was carried out by the Sexual Encounter Profile (SEP) or the
      International Index of Erectile Function (IIEF). Eight trials used SEP3 as study
      endpoint. The rate of positive response to SEP3 (=erectile function sufficient
      for successful intercourse) in the control arms was 20% in 1997 (year of
      publication), 10% in 2003, 19% in 2004, 25% in 2008, 21% in 2010, 67% in 2011,
      10% in 2013, and 22% in 2014. Eight RCTs assessed the IIEF-EF, yet results were
      not reported uniformly. In the control arms the IIEF-EF was 9.2 (year of
      publication 2003), 13.3 (2004), 8.8 (2008), 25% >=22.0 (2008), 17.4 (2010), 58%
      >=26.0 (2011), 9.3 (2013), and 11.6 (2014). Limitations of this analysis are a
      positive selection bias regarding patient recruitment, surgical approach, and the
      non-uniform inclusion and outcome criteria. This systematic analysis of the
      control arms of all RCTs on penile rehabilitation after nerve-sparing RPE shows
      (i) that the rate of undisturbed erectile function is in the range 20-25% in most
      studies and (ii) that these rates have not substantially improved or changed over
      the past 17 years. 

PMID- 26198797
TI  - Increased risk of organic erectile dysfunction in patients with chronic fatigue
      syndrome: a nationwide population-based cohort study.
AB  - Chronic fatigue syndrome (CFS) is a complex disorder characterized by profound
      and persistent fatigue and several comorbidities. CFS was previously reported to
      be associated with female sexual dysfunction. We propose that CFS might also be
      associated with organic erectile dysfunction (organic ED). We conducted a
      retrospective cohort study by using data from the National Health Insurance (NHI)
      Research Database. We identified 2156 male patients who were newly diagnosed with
      CFS between January 1, 2003 and December 31, 2006. After excluding those younger
      than 20 years and prevalent cases, 1976 patients were subjected to analysis, and
      7904 people served as healthy controls. All study subjects were followed up from
      the index date to the date of organic ED diagnosis, withdrawal from the NHI
      program, or the end of 2011. Compared with the non-CFS cohort, the incidence
      density rate of organic ED was 1.88-fold higher than that in the CFS cohort (3.23
      vs. 1.73 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.88 (95%
      CI = 1.26-2.81) when adjusting for sex and comorbidities. The combined impacts of
      patients with CFS and cardiovascular disease (CVD), diabetes mellitus (DM),
      chronic kidney disease (CKD), depression, and anxiety showed a significant by
      joint association with organic ED risk compared with patients with no CFS and no
      counterpart comorbidity. The greatest magnitude of adjusted HR of ED for CFS was
      observed in individuals without any comorbidity (3.87, 1.95-7.66). The incidence
      of organic ED is higher among males aged 40 years and over for both CFS and non
      CFS cohorts. As the number of comorbidity increases, the incidence of organic ED
      increases in males without CFS. Higher incidence of organic ED was observed in
      males with CVD, DM, CKD, depression, or anxiety for both CFS and non-CFS cohorts.

PMID- 26198798
TI  - Expression profiles of NPHP1 in the germ cells in the semen of men with male
      factor infertility.
AB  - NPHP1, the gene that encodes the protein nephrocystin-1 has been identified to be
      mutated in Juvenile Nephronophthisis, an autosomal recessive cystic kidney
      disorder which is the most frequent genetic cause of end-stage renal disease
      (ESRD) in children and young adults. Nphp1-targeted mutant mice studies have
      shown that it did not express renal manifestations of nephronophthisis; instead
      male mice were infertile with oligoteratozoospermia signifying the crucial role
      of Nphp1 in relation to murine spermatogenesis. Whether an aberrant expression of
      NPHP1 in testis might lead to spermatogenic defects in human and ultimately male
      factor infertility is a possibility that have not been investigated so far. In
      this regard, characterization of NPHP1 in spermatozoa from fertile and infertile
      males was carried out by employing RT-PCR, western blotting, and
      immunofluorescence analysis. In all the 23 normozoospermic samples we screened,
      NPHP1 was significantly expressed at the target message and protein level and
      also prominent localization pattern of NPHP1 was observed at the head, midpiece,
      and tail segments of spermatozoa. Conversely, in majority of the 103 infertile
      samples we screened, aberrant pattern of NPHP1 expression was detected at the
      transcript and protein level and abnormal localization pattern of expression was
      observed in spermatozoa. Anomalies detected in infertile cases when compared with
      the normozoospermic controls points to the indispensable role of NPHP1 in
      relation to spermatogenesis. Thus, besides the decisive association with juvenile
      nephronophthisis, our study provides the first direct evidence that NPHP1 is
      associated with male factor infertility and also could be a possible biomarker
      for the assessment of male fertility status. GENBANK NM_000272.3

PMID- 26198799
TI  - Adipose-derived stem cells ameliorate erectile dysfunction after cavernous nerve
      cryoinjury.
AB  - Erectile dysfunction is a common complication following cryotherapy for prostate
      cancer. In this study, we investigated the efficacy of adipose-derived stem cells
      (ADSC) in improving erectile function in a rat model of cavernous nerve (CN)
      cryoinjury and the possible mechanisms. Male rats were intracavernous (IC)
      injected with EdU-labeled ADSC after bilateral CN cryoinjury. Penile tissues were
      harvested for histology and protein level detection at 1 and 4 weeks after ADSC
      administration. Erectile function was assessed prior to tissue harvest. We found
      that erectile function was significantly improved after ADSC treatment via
      promoting nNOS-positive nerve regeneration and cavernous tissue recovery. The
      expression of cleaved caspase 3 (an apoptotic marker) reduced after ADSC
      treatment. Although few EdU-labeled ADSCs were visualized within the penis 4
      weeks after administration, plenty of EdU-labeled ADSCs were found around penile
      dorsal vessels and nerves 1 week after treatment. Furthermore, three neurotrophic
      factors (NGF, VEGF, and Neurturin) were significantly decreased in Cryo group,
      and were partially recovered 1 week after ADSC injection. These results suggested
      that IC injection of ADSC resulted in substantial recoveries of erectile function
      after CN cryoinjury. The effects may be achieved through the elevated level of
      neurotrophic factors in penile tissue and subsequent neuroregenerative effects. 

PMID- 26198800
TI  - Decreased activity of superoxide dismutase in the seminal plasma of infertile men
      correlates with increased sperm deoxyribonucleic acid fragmentation during the
      first hours after sperm donation.
AB  - Sperm DNA fragmentation varies between individuals and is more pronounced with
      increased patient age and time after sperm donation. The intensification of DNA
      fragmentation depends on the balance of the oxidoreductive system, which is
      regulated mainly by two enzymes - superoxide dismutase (SOD) and catalase. The
      objective of this study was to determine the relationship between sperm DNA
      fragmentation dynamics, fertility and seminal SOD and catalase activity. The
      study was conducted in 2013 and 2014 at the Non-Public Health Care Unit 'Ovum
      Reproduction and Andrology' in Lublin, Lublin, Poland, and covered 218 men aged
      25-35 (85 fertile and 133 patients treated for infertility). Percentage of
      fragmented DNA was measured in a modified chromatin dispersion test at four time
      points after sperm donation (t = 0, 3, 6, 12 h). SOD and catalase activities were
      determined spectrophotometrically. We confirmed that the activity of SOD in the
      seminal plasma of men with reproductive disorders was lower compared with fertile
      men. Conversely, no significant correlations were found between fertility and
      catalase activity. Sperm DNA of infertile males was initially more fragmented
      than fertile male sperm DNA. SOD and catalase activity did not correlate with the
      degree of DNA fragmentation in fertile men. In men with reproductive disorders,
      the rate of DNA fragmentation was slow within first 3 h after sperm donation and
      then increased between 6 and 12 h. In this group of infertile men, those with
      higher SOD activity had a lower DNA fragmentation index (DFI) after 12 h, and a
      reduced rate of intensity of fragmentation from 6 to 12 h. Alternatively, higher
      catalase activity among men treated for infertility was accompanied by higher
      initial DFI and higher rate of DNA fragmentation from 6 to 12 h. These results
      highlight the importance of determining a proper time window between sperm
      donation and procedures of assisted reproductive technology. 

PMID- 26198802
TI  - Tracheoesophageal voice after total laryngopharyngectomy reconstruction: Jejunum
      versus radial forearm free flap.
AB  - OBJECTIVE/HYPOTHESIS: Tracheoesophageal (TE) voice restoration after
      laryngopharyngectomy with jejunal (Jej) flap and radial forearm flap (RFF)
      reconstruction has been successfully completed and studied for both techniques,
      but no direct comparisons exist. We undertook this study to directly compare TE
      voice in patients with total laryngopharyngectomy (TLP) reconstruction using the
      Jej and the RFF in a comprehensive and rigorous manner. STUDY DESIGN:
      Retrospective cohort study. METHODS: Forty patients after total laryngectomy or
      TLP were grouped by pharyngeal closure method: 18 primary closure (STL), 10
      jejunal flap (TLP-Jej), and 12 radial forearm flap (TLP-RFF). Voice recordings
      underwent objective acoustic analysis and blinded subjective assessment by
      trained and naive listeners. Quality-of-life (QOL) assessments were obtained in
      all subjects using general health, disease-specific, and voice-specific survey
      tools. RESULTS: All studies groups had similar demographics. Acoustic analysis
      demonstrated no differences in fundamental frequency or intensity levels.
      Subjective assessment demonstrated statistically significant inferior voice
      function of the reconstructed patients (TLP-Jej and TLP-RFF) compared to STL
      subjects for nearly all parameters tested by both naive and trained listeners. No
      differences were noted between TLP-Jej and TLP-RFF subjects for any of the
      parameters evaluated. Overall, trained listeners assessed TE voice more favorably
      compared to naive listeners in a significant manner. The three QOL surveys
      revealed no significant differences between TLP-Jej and TLP-RFF subjects.
      CONCLUSION: Tracheoesophageal voice in TLP-Jej and TLP-RFF subjects was
      equivalent but inferior to STL subjects. Reconstructed subjects had no
      differences in general, disease-specific, and voice-specific quality of life.
      LEVEL OF EVIDENCE: 2b.

PMID- 26198801
TI  - Sperm Lysozyme-Like Protein 1 (SLLP1), an intra-acrosomal oolemmal-binding sperm
      protein, reveals filamentous organization in protein crystal form.
AB  - Sperm lysozyme-like protein 1 (SLLP1) is one of the lysozyme-like proteins
      predominantly expressed in mammalian testes that lacks bacteriolytic activity,
      localizes in the sperm acrosome, and exhibits high affinity for an oolemmal
      receptor, SAS1B. The crystal structure of mouse SLLP1 (mSLLP1) was determined at
      2.15 A resolution. mSLLP1 monomer adopts a structural fold similar to that of
      chicken/mouse lysozymes retaining all four canonical disulfide bonds. mSLLP1 is
      distinct from c-lysozyme by substituting two essential catalytic residues
      (E35T/D52N), exhibiting different surface charge distribution, and by forming
      helical filaments approximately 75 A in diameter with a 25 A central pore
      comprised of six monomers per helix turn repeating every 33 A. Cross-species
      alignment of all reported SLLP1 sequences revealed a set of invariant surface
      regions comprising a characteristic fingerprint uniquely identifying SLLP1 from
      other c-lysozyme family members. The fingerprint surface regions reside around
      the lips of the putative glycan-binding groove including three polar residues
      (Y33/E46/H113). A flexible salt bridge (E46-R61) was observed covering the glycan
      binding groove. The conservation of these regions may be linked to their
      involvement in oolemmal protein binding. Interaction between SLLP1 monomer and
      its oolemmal receptor SAS1B was modeled using protein-protein docking algorithms,
      utilizing the SLLP1 fingerprint regions along with the SAS1B conserved surface
      regions. This computational model revealed complementarity between the conserved
      SLLP1/SAS1B interacting surfaces supporting the experimentally observed
      SLLP1/SAS1B interaction involved in fertilization. 

PMID- 26198803
TI  - Health-related quality of life in patients with Burnout on sick leave:
      descriptive and comparative results from a clinical study.
AB  - PURPOSE: To explore the health-related quality of life (HRQoL), the cause of
      being ill, and the pharmacological treatment in patients on sick leave because of
      Burnout. The HRQoL among these patients was also compared with that of
      individuals who were working full time. METHODS: HRQoL was measured using the
      SWED-QUAL questionnaire, comprising 67 items grouped into 13 subscales, scored
      from 0 (worst) to 100 (best) points, and covering aspects of physical and
      emotional well-being, cognitive function, sleep, general health, social, and
      sexual functioning. The Burnout group (n = 94), mean age 43 years, were on 50%
      sick leave or more. The comparison group consisted of healthy persons (n = 88) of
      similar age and educational level who were working full time. RESULTS: The
      Burnout group had markedly low scores in general. The cause of illness was mainly
      work-related. Psychotropic medication was prescribed for 55%. Significantly lower
      scores were found in the Burnout group than in the comparison group in all
      subscales, p < 0.001. The median differences in scores ranged from 10 to 56
      points. Differences rated by effect size were large, 0.85-2.01. CONCLUSIONS:
      Patients on sick leave because of Burnout rated their HRQoL as very low in
      general, their cause of being ill was mainly work-related, and psychotropic
      medication was prescribed for a majority. Their scores were markedly lower in all
      subscales in comparison with healthy individuals working full time. The study
      adds to our understanding of the situation of patients with Burnout. The results
      can be useful in clinical work and future research.

PMID- 26198804
TI  - Automated swimming activity monitor for examining temporal patterns of toxicant
      effects on individual Daphnia magna.
AB  - Aquatic pollutants are often biologically active at low concentrations and impact
      on biota in combination with other abiotic stressors. Traditional toxicity tests
      may not detect these effects, and there is a need for sensitive high-throughput
      methods for detecting sublethal effects. We have evaluated an automated infra-red
      (IR) light-based monitor for recording the swimming activity of Daphnia magna to
      establish temporal patterns of toxicant effects on an individual level. Activity
      was recorded for 48 h and the sensitivity of the monitor was evaluated by
      exposing D. magna to the reference chemicals K2 Cr2 O7 at 15, 20 and 25  degrees
      C and 2,4-dichlorophenol at 20  degrees C. Significant effects (P < 0.001) of
      toxicant concentrations, exposure time and incubation temperatures were observed.
      At 15  degrees C, the swimming activity remained unchanged for 48 h at sublethal
      concentrations of K2 Cr2 O7 whereas activity at 20 and 25  degrees C was more
      biphasic with decreases in activity occurring after 12-18 h. A similar biphasic
      pattern was observed after 2,4-dichlorophenol exposure at 20  degrees C. EC50
      values for 2,4-dichlorophenol and K2 Cr2 O7 determined from automated recording
      of swimming activity showed increasing toxicity with time corresponding to
      decreases in EC50 of 0.03-0.07 mg l(-1) h(-1) . EC50 values determined after 48 h
      were comparable or lower than EC50 values based on visual inspection according to
      ISO 6341. The results demonstrated that the swimming activity monitor is capable
      of detecting sublethal behavioural effects that are toxicant and temperature
      dependent. The method allows EC values to be established at different time points
      and can serve as a high-throughput screening tool in toxicity testing. Copyright
      (c) 2015 John Wiley & Sons, Ltd.

PMID- 26198805
TI  - Luminescence and advanced mass spectroscopic characterization of sodium zinc
      orthophosphate phosphor for low-cost light-emitting diodes.
AB  - A new rare-earth-free NaZnPO4:Mn(2+) (NZP:Mn) phosphor powder has been developed
      by our group and investigated meticulously for the first time using secondary ion
      mass spectroscopy and chemical imaging techniques. The studies confirmed the
      effective incorporation of Mn(2+) into the host lattice, resulting in an
      enhancement of photoluminescence intensity. Phase purity has been verified and
      structure parameters have been determined successfully by Rietveld refinement
      studies. The NZP:Mn phosphor powder exhibits strong absorption bands in the
      ultraviolet and visible (300-470 nm) regions with a significant broad yellow
      green (~543 nm) emission due to the characteristic spin forbidden d-d transition
      ((4)T1->(6)A1) of Mn(2+) ions, indicating weak crystal field strength at the zinc
      replaced manganese site. The decay constants are a few milliseconds, which is a
      pre-requisite for applications in many display devices. The results obtained
      suggest that this new phosphor powder will find many interesting applications in
      semiconductor physics, as cost-effective light-emitting diodes (LEDs), as solar
      cells and in photo-physics.

PMID- 26198806
TI  - Bruch's Membrane Opening Minimum Rim Width and Retinal Nerve Fiber Layer
      Thickness in a Normal White Population: A Multicenter Study.
AB  - PURPOSE: Conventional optic disc margin-based neuroretinal rim measurements lack
      a solid anatomic and geometrical basis. An optical coherence tomography (OCT)
      index, Bruch's membrane opening minimum rim width (BMO-MRW), addresses these
      deficiencies and has higher diagnostic accuracy for glaucoma. We characterized
      BMO-MRW and peripapillary retinal nerve fiber layer thickness (RNFLT) in a normal
      population. DESIGN: Multicenter cross-sectional study. PARTICIPANTS: Normal white
      subjects. METHODS: An approximately equal number of subjects in each decade group
      (20-90 years of age) was enrolled in 5 centers. Subjects had normal ocular and
      visual field examination results. We obtained OCT images of the optic nerve head
      (24 radial scans) and peripapillary retina (1 circular scan). The angle between
      the fovea and BMO center (FoBMO angle), relative to the horizontal axis of the
      image frame, was first determined and all scans were acquired and analyzed
      relative to this eye-specific FoBMO axis. Variation in BMO-MRW and RNFLT was
      analyzed with respect to age, sector, and BMO shape. MAIN OUTCOME MEASURES: Age
      related decline and between-subject variability in BMO-MRW and RNFLT. RESULTS:
      There were 246 eyes of 246 subjects with a median age of 52.9 years (range, 19.8
      87.3 years). The median FoBMO angle was -6.7 degrees  (range, 2.5 degrees  to 
      17.5 degrees ). The BMO was predominantly vertically oval with a median area of
      1.74 mm(2) (range, 1.05-3.40 mm(2)). Neither FoBMO angle nor BMO area was
      associated with age or axial length. Both global mean BMO-MRW and RNFLT declined
      with age at a rate of -1.34 MUm/year and -0.21 MUm/year, equivalent to 4.0% and
      2.1% loss per decade of life, respectively. Sectorially, the most rapid decrease
      occurred inferiorly and the least temporally; however, the age association was
      always stronger with BMO-MRW than with RNFLT. There was a modest relationship
      between mean global BMO-MRW and RNFLT (r = 0.35), whereas sectorially the
      relationship ranged from moderate (r = 0.45, inferotemporal) to nonexistent (r =
      0.01, temporal). CONCLUSIONS: There was significant age-related loss of BMO-MRW
      in healthy subjects and notable differences between BMO-MRW and RNFLT in their
      relationship with age and between each other. Adjusting BMO-MRW and RNFLT for age
      and sector is important in ensuring optimal diagnostics for glaucoma.

PMID- 26198807
TI  - Papilledema Outcomes from the Optical Coherence Tomography Substudy of the
      Idiopathic Intracranial Hypertension Treatment Trial.
AB  - PURPOSE: To assess treatment efficacy using spectral-domain (SD) optical
      coherence tomography (OCT) measurements of papilledema in the Idiopathic
      Intracranial Hypertension Treatment Trial (IIHTT), which evaluated the effects of
      acetazolamide and weight management and of placebo and weight management in eyes
      with mild visual loss. DESIGN: Randomized double-masked control clinical trial of
      acetazolamide plus weight management compared with placebo plus weight management
      in subjects with mild visual field loss and previously untreated idiopathic
      intracranial hypertension (IIH). PARTICIPANTS: Eighty-nine (43 acetazolamide
      treated, 46 placebo treated) of 165 subjects meeting IIHTT entry criteria.
      METHODS: Subjects underwent perimetry, papilledema grading (Frisen method), high-
      and low-contrast visual acuity, and SD OCT imaging at study entry and 3 and 6
      months. Study eye results (worse perimetric mean deviation [PMD]) were used for
      most analyses. MAIN OUTCOME MEASURES: Retinal nerve fiber layer (RNFL) thickness,
      total retinal thickness (TRT), optic nerve (ONH) volume, and retinal ganglion
      cell layer (RGCL) measurements derived using 3-dimensional segmentation. RESULTS:
      Study entry OCT values were similar in both treatment groups. At 6 months, the
      acetazolamide group had greater reduction than the placebo group for RNFL
      thickness (175 MUm vs. 89 MUm; P = 0.001), TRT (220 MUm vs. 113 MUm; P = 0.001),
      and ONH volume (4.9 mm(3) vs. 2.1 mm(3); P = 0.001). The RNFL thickness (P =
      0.01), TRT (P = 0.003), and ONH volume (P = 0.002) measurements also showed
      smaller increases in subjects who lost 6% or more of study entry weight. The
      acetazolamide (3.6 MUm) and placebo (2.1 MUm) groups showed minor RGCL thinning
      (P = 0.06). The RNFL thickness, TRT, and ONH volume measurements showed moderate
      correlations (r = 0.48-0.59; P <= 0.0001) with Frisen grade. The 14 eyes with
      RGCL thickness less than the fifth percentile of controls had worse PMD (P =
      0.001) than study eyes with RGCL in the fifth percentile or more. CONCLUSIONS: In
      IIH, acetazolamide and weight loss effectively improve RNFL thickness, TRT, and
      ONH volume swelling measurements resulting from papilledema. In contrast to the
      strong correlation at baseline, OCT measures at 6 months show only moderate
      correlations with papilledema grade.

PMID- 26198808
TI  - Intravitreal Aflibercept for Diabetic Macular Edema: 100-Week Results From the
      VISTA and VIVID Studies.
AB  - PURPOSE: To compare efficacy and safety of 2 dosing regimens of intravitreal
      aflibercept injection (IAI) with macular laser photocoagulation for diabetic
      macular edema (DME). DESIGN: Two similarly designed, randomized, phase 3 trials,
      VISTA(DME) and VIVID(DME). PARTICIPANTS: Patients (eyes; n=872) with type 1 or 2
      diabetes mellitus who had DME with central involvement. METHODS: Eyes received
      IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8),
      or laser control. MAIN OUTCOME MEASURES: The primary end point was mean change
      from baseline in best-corrected visual acuity (BCVA) at week 52. This report
      presents the 100-week results including mean change from baseline in BCVA,
      proportion of eyes that gained >=15 letters, and proportion of eyes with a >=2
      step improvement in the Diabetic Retinopathy Severity Scale (DRSS) score.
      RESULTS: Mean BCVA gain from baseline to week 100 with IAI 2q4, IAI 2q8, and
      laser control was 11.5, 11.1, and 0.9 letters (P < 0.0001) in VISTA and 11.4,
      9.4, and 0.7 letters (P < 0.0001) in VIVID, respectively. The proportion of eyes
      that gained >=15 letters from baseline at week 100 was 38.3%, 33.1%, and 13.0% (P
      < 0.0001) in VISTA and 38.2%, 31.1%, and 12.1% (P <= 0.0001) in VIVID. The
      proportion of eyes that lost >=15 letters at week 100 was 3.2%, 0.7%, and 9.7% (P
      <= 0.0220) in VISTA and 2.2%, 1.5%, and 12.9% (P <= 0.0008) in VIVID.
      Significantly more eyes in the IAI 2q4 and 2q8 groups versus those in the laser
      control group had a >=2 step improvement in the DRSS score in both VISTA (37.0%
      and 37.1% vs. 15.6%; P < 0.0001) and VIVID (29.3% and 32.6% vs. 8.2%; P <=
      0.0004). In an integrated safety analysis, the most frequent serious ocular
      adverse event was cataract (2.4%, 1.0%, and 0.3% for 2q4, 2q8, and control).
      CONCLUSIONS: In both VISTA and VIVID, the 52-week visual and anatomic superiority
      of IAI over laser control was sustained through week 100, with similar efficacy
      in the 2q4 and 2q8 groups. Safety in these studies was consistent with the known
      safety profile of IAI.

PMID- 26198809
TI  - Estimating Lead Time Gained by Optical Coherence Tomography in Detecting Glaucoma
      before Development of Visual Field Defects.
AB  - PURPOSE: To estimate the diagnostic accuracy and lead time gained by retinal
      nerve fiber layer (RNFL) thickness measurements from optical coherence tomography
      (OCT) for detecting glaucoma before the development of visual field defects.
      DESIGN: Observational cohort study. PARTICIPANTS: The study group included 75
      eyes of 75 patients suspected of having glaucoma. These eyes had normal standard
      automated perimetry (SAP) at baseline and demonstrated repeatable (3 consecutive)
      abnormal tests during a median follow-up of 6.3 years. A control group of 75 eyes
      of 75 healthy subjects matched by age and number of OCT tests during follow-up
      was included. METHODS: The RNFL thickness measurements were obtained at the time
      of development of the earliest SAP defect (time 0) and also at times -1, -2, -3,
      and so forth, corresponding to 1 year, 2 years, 3 years, and so forth, before the
      development of field loss. The OCT measurements at corresponding intervals were
      analyzed for controls. Time-dependent receiver operating characteristic (ROC)
      curves were used to evaluate diagnostic accuracy of OCT. MAIN OUTCOME MEASURES:
      Areas and sensitivities of ROC curve at fixed specificities at different times
      before development of field loss. RESULTS: At the date of conversion to the
      earliest visual field defect (time 0), mean +/- standard deviation average RNFL
      thickness was 75.0+/-9.8 MUm in glaucomatous eyes and 90.6+/-8.0 MUm for controls
      (P < 0.001). Significant differences were seen up to 8 years before development
      of visual field defects (86.3+/-8.2 MUm vs. 91.4+/-7.6 MUm, respectively; P =
      0.021). The ROC curve areas decreased with increasing times before detection of
      field defects. At times 0, -4, and -8 years, ROC curve areas were 0.87, 0.77, and
      0.65, respectively. At 95% specificity, up to 35% of eyes had abnormal average
      RNFL thickness 4 years before development of visual field loss and 19% of eyes
      had abnormal results 8 years before field loss. CONCLUSIONS: Assessment of RNFL
      thickness with OCT was able to detect glaucomatous damage before the appearance
      of visual field defects on SAP. In many subjects, significantly large lead times
      were seen when applying OCT as an ancillary diagnostic tool.

PMID- 26198810
TI  - Adverse drug reactions in a primary care population prescribed non-steroidal anti
      inflammatory drugs.
AB  - OBJECTIVE: To determine how often patients with musculoskeletal (MSK) complaints
      prescribed a non-steroidal anti-inflammatory drug (NSAID) subsequently consult
      their general practitioner (GP) with a non-serious adverse drug reaction (ADR).
      DESIGN: Cohort study. SETTING: A healthcare database containing the electronic GP
      medical records of over 1.5 million patients throughout the Netherlands.
      PATIENTS: A total of 16 626 adult patients with MSK complaints prescribed an
      NSAID. MAIN OUTCOME MEASURES: The patients' medical records were manually
      assessed for the duration of NSAID use for a maximum of two months, and
      consultations for complaints predefined as potential ADRs were identified.
      Subsequently, the likelihood of an association with the NSAID use was assessed
      and these potential ADRs were categorized as likely, possible, or unlikely ADRs.
      RESULTS: In total, 961 patients (6%) consulted their GP with 1227 non-serious
      potential ADRs. In 174 patients (1%) at least one of these was categorized as a
      likely ADR, and in a further 408 patients (2.5%) at least one was categorized as
      a possible ADR. Dyspepsia was the most frequent likely ADR, followed by diarrhoea
      and dyspnoea (respectively 34%, 8%, and 8% of all likely ADRs). CONCLUSION: Of
      the patients with MSK complaints prescribed an NSAID, almost one in 30 patients
      re-consulted their GP with a complaint likely or possibly associated with the use
      of this drug. The burden of such consultations for non-serious ADRs should be
      taken into account by GPs when deciding whether treatment with an NSAID is
      appropriate.

PMID- 26198811
TI  - HDAC6 and RhoA are novel players in Abeta-driven disruption of neuronal polarity.
AB  - Maintenance of neuronal polarity and regulation of cytoskeletal dynamics are
      vital during development and to uphold synaptic activity in neuronal networks.
      Here we show that soluble beta-amyloid (Abeta) disrupts actin and microtubule
      (MT) dynamics via activation of RhoA and inhibition of histone deacetylase 6
      (HDAC6) in cultured hippocampal neurons. The contact of Abeta with the
      extracellular membrane promotes RhoA activation, leading to growth cone collapse
      and neurite retraction, which might be responsible for hampered neuronal
      pathfinding and migration in Alzheimer's disease (AD). The inhibition of HDAC6 by
      Abeta increases the level of heterodimeric acetylated tubulin and acetylated tau,
      both of which have been found altered in AD. We also find that the loss of HDAC6
      activity perturbs the integrity of axon initial segment (AIS), resulting in
      mislocalization of ankyrin G and increased MT instability in the AIS concomitant
      with loss of polarized localization of tau and impairment of action potential
      firing. 

PMID- 26198812
TI  - Drug compound characterization by mass spectrometry imaging in cancer tissue.
AB  - MALDI mass spectrometry imaging (MSI) provides a technology platform that allows
      the accurate visualization of unlabeled small molecules within the two
      dimensional spaces of tissue samples. MSI has proven to be a powerful tool-box
      concept in the development of new drugs. MSI allows unlabeled drug compounds and
      drug metabolites to be detected and identified and quantified according to their
      mass-to-charge ratios (m/z) at high resolution in complex tissue environments.
      Such drug characterization in situ, by both spatial and temporal behaviors within
      tissue compartments, provide new understandings of the dynamic processes
      impacting drug uptake and metabolism at the local sites targeted by therapy.
      Further, MSI in combination with histology and immunohistochemistry, provides the
      added value of defining the context of cell biology present at the sites of drug
      localization thus providing invaluable information relating to treatment
      efficacy. In this report we provide mass spectrometry imaging data within various
      cancers such as malignant melanoma in patients administered with vemurafenib, a
      protein kinase inhibitor that is targeting BRAF mutated proteins and that has
      shown significant efficacy in restraining disease progression. We also provide an
      overview of other examples of the new generation of targeted drugs, and
      demonstrate the data on personalized medicine drugs localization within tumor
      compartments within in vivo models. In these cancer models we provide detailed
      data on drug and target protein co-localization of YCG185 and sunitinib. These
      drugs are targeting VEGFR2 within the angiogenesis mechanism. Our ability to
      resolve drug uptake at targeted sites of directed therapy provides important
      opportunities for increasing our understanding about the mode of action of drug
      activity within the environment of disease. 

PMID- 26198813
TI  - AIM2 Blocks Colon Cancer in Three Ways.

PMID- 26198815
TI  - Nipple discharge.

PMID- 26198814
TI  - PRC2 inhibition counteracts the culture-associated loss of engraftment potential
      of human cord blood-derived hematopoietic stem and progenitor cells.
AB  - Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for
      transplantation approaches. However, the amount of cells per donor is limited and
      culture expansion of CB-HSCs is accompanied by a loss of engraftment potential.
      In order to analyze the molecular mechanisms leading to this impaired potential
      we profiled global and local epigenotypes during the expansion of human CB
      hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells
      were cultured in serum-free medium together with SCF, TPO, FGF, with or without
      Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the
      STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells.
      Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending
      on the cytokine cocktail, cells show different H3K4me3 and H3K27me3 levels.
      Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3
      levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of
      H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture
      associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our
      data reveal chromatin dynamics that underlie the culture-associated loss of
      engraftment potential. We identify PRC2 component EZH2 as being involved in the
      loss of engraftment potential during the in vitro expansion of HPSCs. 

PMID- 26198816
TI  - Stress index for positive end-expiratory pressure titration in prone position: a
      piglet study.
AB  - BACKGROUND: Prone position ventilation is an important treatment for acute
      respiratory distress syndrome (ARDS), but chest wall elastance increases in prone
      position ventilation, and stress index may not reflect the changes in lung
      mechanics. We therefore investigated the effects of stress index guided PEEP
      titration on pulmonary mechanics and hemodynamics in the prone position in a
      piglet acute lung injury model. METHODS: Ten piglets with severe lavage-induced
      lung injury were mechanically ventilated in a decremental PEEP trial after full
      lung recruitment in the prone position. Stress-index PEEP was the level at which
      the airway pressure stress index was 1, and open-lung PEEP was the level at which
      it was required to keep the lung open according to computed tomography (CT)
      scans. Respiratory mechanics, blood gases, hemodynamics, and whole-lung CT were
      recorded at the two PEEP levels. RESULTS: Respiratory system elastance and lung
      elastance were improved in the prone position but the ratio of chest wall
      elastance and respiratory system elastance was higher in the prone position.
      There was no significant difference between open-lung and stress-index guided
      PEEPs in the prone position (P = 0.46). There was no significant difference
      between collapsed lung volume (P = 0.07) and hyperinflation lung volume (P =
      0.76) in the two groups. Similarly, there was no significant difference between
      open-lung and stress-index guided PEEPs in terms of oxygenation index (P = 0.95)
      and PaCO2 (P = 0.42). CONCLUSIONS: Stress index can be used to titrate PEEP in
      the prone position in a surfactant-depleted lung injury model.

PMID- 26198817
TI  - How a radial focal incision influences the internal shear distribution in
      articular cartilage with respect to its zonally differentiated microanatomy.
AB  - Articular surface fibrillation and the loss of both transverse interconnectivity
      and zonal differentiation are indicators of articular cartilage (AC)
      degeneration. However, exactly how these structural features affect the load
      redistributing properties of cartilage is still poorly understood. This study
      investigated how a single radial incision made to varying depths with respect to
      the primary zones of AC influenced its deformation response to compression. Three
      depths of incision were applied to cartilage-on-bone tissue blocks: one not
      exceeding the transition zone; one into the mid-radial zone; and one down to the
      calcified cartilage. Also included were non-incised controls. All samples were
      compressed to a near-equilibrium strain using a flat-faced indenter that
      incorporated a central relief channel within which the incision could be
      positioned lengthwise along the channel axis. Employing fixation under load
      followed by decalcification, the structural responses of the cartilage-on-bone
      samples were investigated. The study provides an analysis of the micro
      morphological response that is characteristic of a completely normal cartilage-on
      bone system but which contains a defined degree of disruption induced by the
      focal radial incision. The resulting loss of transverse continuity of the
      cartilage with respect to its zonally differentiated structure is shown to lead
      to an altered pattern of internal matrix shear whose intensity varies with
      incision depth. 

PMID- 26198818
TI  - Childhood maltreatment is associated with altered frontolimbic neurobiological
      activity during wakefulness in adulthood.
AB  - Childhood maltreatment can disturb brain development and subsequently lead to
      adverse socioemotional and mental health problems across the life span. The long
      term association between childhood maltreatment and resting-wake brain activity
      during adulthood is unknown and was examined in the current study. Forty-one
      medically stable and medication-free military veterans (M = 29.31 +/- 6.01 years,
      78% male) completed a battery of clinical assessments and had [18F]
      fluorodeoxyglucose positron emission tomography neuroimaging scans during quiet
      wakefulness. After statistically adjusting for later-life trauma and mental
      health problems, childhood maltreatment was negatively associated with brain
      activity within a priori defined regions that included the left orbital frontal
      cortex and left hippocampus. Childhood maltreatment was significantly associated
      with increased and decreased brain activity within six additional whole-brain
      clusters that included the frontal, parietal-temporal, cerebellar, limbic, and
      midbrain regions. Childhood maltreatment is associated with altered neural
      activity in adulthood within regions that are involved in executive functioning
      and cognitive control, socioemotional processes, autonomic functions, and
      sleep/wake regulation. This study provides support for taking a life span
      developmental approach to understanding the effects of early-life maltreatment on
      later-life neurobiology, socioemotional functioning, and mental health. 

PMID- 26198821
TI  - The Impact of Community Based Health Insurance in Enhancing Better Accessibility
      and Lowering the Chance of Having Financial Catastrophe Due to Health Service
      Utilization: A Case Study of Savannakhet Province, Laos.
AB  - The Lao population mostly relies on out-of-pocket expenditures for health care
      services. This study aims to determine the role of community-based health
      insurance in making health care services accessible and in preventing financial
      catastrophe resulting from personal payment for inpatient services. A cross
      sectional study design was applied. Data collection involved 126 insured and 126
      uninsured households in identical study sites. Two logistic regression models
      were used to predict and compare the probability of hospitalization and financial
      catastrophe that occurred in both insured and uninsured households within the
      previous year. The findings show that insurance status does not significantly
      improve accessibility and financial protection against catastrophic expenditure.
      The reason is relatively simple, as catastrophic health expenditure refers to a
      total out-of-pocket payment equal to or more than 40% of household income minus
      subsistence. When household income declines as a result of inability to work due
      to illness, the 40% threshold is quickly reached. Despite this, results suggest
      that insured households are not significantly better off under community-based
      health insurance. However, compared to uninsured households, insured households
      do have better accessibility and a lower probability of reaching the financial
      catastrophe threshold.

PMID- 26198819
TI  - Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine
      TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid
      factors.
AB  - BACKGROUND: Intracranial aneurysm (IA) is often asymptomatic until the time of
      rupture resulting in subarachnoid hemorrhage (SAH).There is no precise
      biochemical or phenotype marker for diagnosis of aneurysm. Environmental risk
      factors that associate with IA can result in modifying the effect of inherited
      genetic factors and thereby increase the susceptibility to SAH. In addition
      subsequent to aneurismal rupture, the nature and quantum of inflammatory response
      might be critical for repair. Therefore, genetic liability to inflammatory
      response caused by polymorphisms in cytokine genes might be the common
      denominator for gene and environment in the development of aneurysm and
      complications associated with rupture. METHODS: Functionally relevant
      polymorphisms in the pro- and anti-inflammatory cytokine genes IL-1 complex
      (IL1A, IL1B, and IL1RN), TNFA, IFNG, IL3, IL6, IL12B, IL1RN, TGFB1, IL4, and
      IL10] were screened in radiologically confirmed 220 IA patients and 250 controls
      from genetically stratified Malayalam-speaking Dravidian ethnic population of
      south India. Subgroup analyses with genetic and environmental variables were also
      carried out. RESULTS: Pro-inflammatory cytokines TNFA rs361525, IFNG rs2069718,
      and anti-inflammatory cytokine IL10 rs1800871 and rs1800872 were found to be
      significantly associated with IA, independent of epidemiological factors. TGFB1
      rs1800469 polymorphism was observed to be associated with IA through co-modifying
      factors such as hypertension and gender. Functional prediction of all the
      associated SNPs of TNFA, IL10, and TGFB1 indicates their potential role in
      transcriptional regulation. Meta-analysis further reiterates that IL1 gene
      cluster and IL6 were not associated with IA. CONCLUSIONS: The study suggests that
      chronic exposure to inflammatory response mediated by genetic variants in pro
      inflammatory cytokines TNFA and IFNG could be a primary event, while stochastic
      regulation of IL10 and TGFB1 response mediated by comorbid factors such as
      hypertension may augment the pathogenesis of IA through vascular matrix
      degradation. The implication and interaction of these genetic variants under a
      specific environmental background will help us identify the resultant phenotypic
      variation in the pathogenesis of intracranial aneurysm. Identifying genetic risk
      factors for inflammation might also help in understanding and addressing the
      posttraumatic complications following the aneurismal rupture.

PMID- 26198820
TI  - Yoga in adult cancer: an exploratory, qualitative analysis of the patient
      experience.
AB  - BACKGROUND: Some patients receiving treatment in conventional health care systems
      access therapeutic yoga outside their mainstream care to improve cancer symptoms.
      Given the current knowledge gap around patient preferences and documented
      experiences of yoga in adult cancer, this study aimed to describe patient
      reported benefits, barriers and characteristics of programming for yoga practice
      during conventional treatment. METHODS: In depth semi-structured interviews
      (n=10) were conducted in men and women recruited from cancer care clinics in
      Vancouver, Canada using a purposive sampling technique. The exploratory
      interviews were audio-recorded, transcribed and analyzed using Interpretive
      Description methodology and constant comparative analysis methods. RESULTS: Four
      themes emerged from the data to address our research objectives: patient
      perceived benefits of yoga, reasons and motivations for practising yoga, hurdles
      and barriers to practising yoga, and advice for effective yoga program delivery
      in adult cancer. Several patients reported yoga reduced stress and other symptoms
      associated with cancer treatment. Thematic analysis found the social dimension of
      group yoga was important, as well as yoga's ability to encourage personal
      empowerment and awareness of physical body and self. Barriers to yoga adherence
      from the patient perspective included lack of time, scheduling conflicts and
      worries about financial burden. CONCLUSION: This small, diverse sample of
      patients reported positive experiences and no adverse effects following yoga
      practice for management of cancer and its symptoms. Results of this qualitative
      study identified patient-reported preferences, barriers and characteristics of
      yoga intervention optimal during adult cancer treatment.

PMID- 26198822
TI  - Serological aggravation of autoimmune thyroid disease in two cases receiving
      nivolumab.
AB  - Nivolumab, a blockade of programmed cell death 1, is now administrated for
      advanced malignant melanomas. Nivolumab-associated adverse events include organ
      specific autoimmune disorders; autoimmune thyroid disease, vitiligo and insulin
      dependent diabetes. However, predisposed persons are currently unknown. Here, we
      report serological aggravation of autoimmune thyroid disease in two cases
      receiving nivolumab: one with Hashimoto disease and another with probable
      subclinical Hashimoto disease. We should verify if nivolumab-related
      hypothyroidism and hyperthyroidism are predisposed to occur in euthyroid
      individuals with subclinical autoimmune thyroid disease. 

PMID- 26198823
TI  - Cardio-oncology: a special focus issue from Future Oncology.

PMID- 26198824
TI  - Should vascular effects of newer treatments be addressed more completely?

PMID- 26198825
TI  - Left ventricular ejection fraction in advanced cancer patients: a valuable
      prognostic tool?

PMID- 26198826
TI  - Melatonin: a protective role against doxorubicin-induced cardiotoxicity.

PMID- 26198827
TI  - Cardio-oncology: a tremendous opportunity to improve patient care.
AB  - A cardiologist at Vanderbilt University (TN, USA), Daniel J Lenihan is President
      of the International CardiOncology Society-North America. In 1988, Daniel
      graduated from the University of Tennessee College of Medicine at Memphis and did
      his residency at Wright-Patterson Air Force Base in Dayton (OH, USA). Ultimately,
      he gained a cardiology fellowship from the University of Cincinnati (OH, USA) and
      went on to become Professor and Director of Cardiovascular Research in the
      Department of Cardiology at The University of Texas MD Anderson Cancer (TX, USA).
      He now works as Professor of Medicine and Director of Clinical Research in the
      Division of Cardiovascular Medicine, Vanderbilt University Medical Center,
      Nashville (TN, USA) specializing in advanced heart failure medicine and cardio
      oncology. For over 20 years, he has been active in clinical research in heart
      failure, and the main focuses of his work have included hemodynamic assessments,
      angiogenic growth factor response, novel cardiac biomarkers and optimal methods
      to prevent or detect heart failure at the earliest stage possible in patients
      undergoing treatment for cancer.

PMID- 26198828
TI  - Optimizing cardio-oncology programs for cancer patients.

PMID- 26198829
TI  - Radiation-induced coronary artery disease: a second survivorship challenge?

PMID- 26198830
TI  - Should the 'echo guidelines' be followed in cancer patients?

PMID- 26198831
TI  - The discipline of onco-cardiology.

PMID- 26198832
TI  - Screening and intervention for treatment-related cardiac dysfunction in childhood
      cancer survivors.

PMID- 26198833
TI  - The use of myocardial strain and newer echocardiography imaging techniques in
      cancer patients.

PMID- 26198834
TI  - Crizotinib-induced cardiotoxicity: the importance of a proactive monitoring and
      management.
AB  - Crizotinib is a multitarget tyrosine kinase inhibitor and it represents the
      standard of care in patients with anaplastic lymphoma kinase translocated non
      small-cell lung cancer. Crizotinib is generally well tolerated and the most
      frequent adverse events include gastrointestinal effects, visual disorders,
      edema, fatigue and liver enzyme abnormalities. However, due to the increasing
      clinical experience with crizotinib, other toxicities are emerging, such as Q
      wave T-wave interval prolongation and bradycardia. In the current review we will
      focus on the management of crizotinib-related cardiotoxicity. 

PMID- 26198835
TI  - Carotid artery inflammation associated with gemcitabine-based therapy: a special
      report.
AB  - Vasculitis is an inflammation that can present as acute or chronic in nature,
      which causes changes in the walls of blood vessels, including thickening,
      weakening, narrowing and scarring. Gemcitabine, an antimetabolite
      chemotherapeutic agent, is generally well tolerated with a favorable side effect
      profile. However, there is increasing evidence that it is associated with
      vasculitis, which can affect small and large vessels. In this case report, we
      report a patient who has experienced fever with severe tenderness over right
      carotid artery, which occurred on the fifth day after the administration of
      gemcitabine. The exact mechanism of gemcitabine-induced vasculitis is unknown but
      cessation of gemcitabine and initiation of anti-inflammatory treatment appears to
      aid in the resolution of the clinical syndrome. 

PMID- 26198836
TI  - Cardio-oncology: an ongoing evolution.
AB  - Cancer survivorship has been greatly impacted with the development of modern
      cancer treatments. While significant strides have been made in managing many
      types of cancer, now physicians face new challenges. Over the past decades,
      cardiovascular events in cancer survivors have increased in prevalence, driving
      the development of multidisciplinary cardio-oncology programs. Additionally, as
      cancer patients live longer, their risk of developing secondary cardiovascular
      events increases. The rapid development of novel cancer therapies will continue
      to generate questions of cardiac risk and cardiac protection in cancer patients
      over time. We wish to outline the development of cardio-oncology in its present
      state, and provide future perspectives for the discipline. 

PMID- 26198837
TI  - Radiation-related heart and vascular disease.
AB  - Improvement in cancer therapy has led to increasing number of cancer survivors,
      some of whom have previously been treated with mediastinal radiation. Cardiac
      complication may manifest years after completion of radiation therapy. Hence long
      term follow-up is essential in these patients. In this paper, we have discussed
      the short- and long-term cardiovascular side effects of radiation therapy. 

PMID- 26198838
TI  - Identifying cancer patients at risk for cardiotoxicity.
AB  - Improvements in therapies have significantly changed survival of cancer patients.
      However, the clinical history and oncologic treatment put cancer patients at
      higher risk for developing cardiovascular problems. Anthracyclines, but also the
      targeted therapy and angiogenesis inhibitors, are all treatments associated with
      cardiotoxicity. The most common adverse event is a reduction in left ventricular
      ejection fraction that may progress to overt heart failure. Recognition of a
      cardiac impairment during or after a potential cardiotoxic treatment requires a
      stringent assessment of clinical symptoms and signs of heart failure associated
      with an evaluation of the left ventricular ejection fraction, which, however,
      detects the damage already installed. Circulating cardiac biomarkers are
      promising in detecting cardiotoxicity and will likely change the approach for
      identifying patients at risk. 

PMID- 26198839
TI  - Strategies for early detection of cardiotoxicities from anticancer therapy in
      adults: evolving imaging techniques and emerging serum biomarkers.
AB  - Significant advances have been made in detecting cancer therapeutics-related
      cardiac dysfunction with serum biomarkers, cardiovascular MRI, echocardiography
      and multi-modality approaches. Serum biomarkers, notably cardiac troponins and
      natriuretic peptides, have been evaluated for their prognostic ability in
      predicting left ventricular dysfunction. Imaging modalities, such as
      cardiovascular MRI and echocardiography, have been used for cardiac surveillance
      of patients with cancer undergoing chemotherapy. Developments in imaging,
      specifically myocardial deformation imaging, also known as strain, have been
      shown to be sensitive tools in detecting early changes in cardiac function. This
      review aims to synthesize the evidence that supports emerging serum biomarkers
      and complementary imaging modalities that continue to enhance the detection of
      cancer therapeutics-related cardiac dysfunction. 

PMID- 26198840
TI  - Nonheme Fe(IV) Oxo Complexes of Two New Pentadentate Ligands and Their Hydrogen
      Atom and Oxygen-Atom Transfer Reactions.
AB  - Two new pentadentate {N5} donor ligands based on the N4Py (N4Py = N,N-bis(2
      pyridylmethyl)-N-bis(2-pyridyl)methylamine) framework have been synthesized, viz.
      [N-(1-methyl-2-benzimidazolyl)methyl-N-(2-pyridyl)methyl-N-(bis-2-pyridyl
      methyl)amine] (L(1)) and [N-bis(1-methyl-2-benzimidazolyl)methyl-N-(bis-2
      pyridylmethyl)amine] (L(2)), where one or two pyridyl arms of N4Py have been
      replaced by corresponding (N-methyl)benzimidazolyl-containing arms. The complexes
      [Fe(II)(CH3CN)(L)](2+) (L = L(1) (1); L(2) (2)) were synthesized, and reaction of
      these ferrous complexes with iodosylbenzene led to the formation of the ferryl
      complexes [Fe(IV)(O)(L)](2+) (L = L(1) (3); L(2) (4)), which were characterized
      by UV-vis spectroscopy, high resolution mass spectrometry, and Mossbauer
      spectroscopy. Complexes 3 and 4 are relatively stable with half-lives at room
      temperature of 40 h (L = L(1)) and 2.5 h (L = L(2)). The redox potentials of 1
      and 2, as well as the visible spectra of 3 and 4, indicate that the ligand field
      weakens as ligand pyridyl substituents are progressively substituted by (N
      methyl)benzimidazolyl moieties. The reactivities of 3 and 4 in hydrogen-atom
      transfer (HAT) and oxygen-atom transfer (OAT) reactions show that both complexes
      exhibit enhanced reactivities when compared to the analogous N4Py complex
      ([Fe(IV)(O)(N4Py)](2+)), and that the normalized HAT rates increase by
      approximately 1 order of magnitude for each replacement of a pyridyl moiety;
      i.e., [Fe(IV)(O)(L(2))](2+) exhibits the highest rates. The second-order HAT rate
      constants can be directly related to the substrate C-H bond dissociation
      energies. Computational modeling of the HAT reactions indicates that the reaction
      proceeds via a high spin transition state. 

PMID- 26198841
TI  - Ulnar Rotation Osteotomy for Congenital Radial Head Dislocation.
AB  - PURPOSE: To evaluate an ulnar rotation osteotomy for congenital anterior
      dislocation of the radial head. METHODS: Nine patients (5 boys and 4 girls aged 6
      to 13 years) with congenital anterior dislocation of the radial head were treated
      with ulnar rotation osteotomy. Magnetic resonance imaging of the elbow showed the
      proximal radioulnar joint on the anterior-lateral side of the ulna rather than on
      the lateral side in patients with congenital anterior dislocation of the radial
      head. On the basis of this finding, we performed an osteotomy on the ulna and
      laterally rotated the proximal radioulnar joint achieving radial head reduction
      and restoring the anatomical relationship between the radial head and the
      capitellum. Clinical and radiographical evaluation of the elbow was performed
      before surgery and at postoperative follow-up. RESULTS: All patients were
      followed for 13 to 45 months after surgery. Elbow radiography showed that the
      radiocapitellar joint was reduced in all patients at the last follow-up visit and
      that the carrying angle was decreased relative to that in the preoperative
      condition. Elbow stability and the range of elbow flexion motion were improved at
      the last follow-up. We did not observe ulnar osteotomy site nonunion or elbow
      osteoarthritis in these patients. Furthermore, radial head dislocation did not
      recur. CONCLUSIONS: At early follow-up, ulnar rotation osteotomy was a safe and
      effective method for the treatment of congenital anterior dislocation of the
      radial head. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 26198843
TI  - Severe liver failure due to influenza A infection in a hemodialysis patient.
AB  - Patients with influenza infection most commonly present with upper and
      occasionally lower respiratory tract symptoms. However, extrapulmonary
      presentations such as hepatitis are infrequently observed. We report a case of a
      hemodialysis patient with influenza A infection who presented with severe
      hepatitis and liver failure, while his respiratory symptoms were mild. It is
      important to recognize influenza infection as an unexplained cause of hepatitis
      and liver failure. In our case, liver failure resolved with supportive treatment.

PMID- 26198842
TI  - Efficacy of galactose and adalimumab in patients with resistant focal segmental
      glomerulosclerosis: report of the font clinical trial group.
AB  - BACKGROUND: Patients with resistant focal segmental glomerulosclerosis (FSGS) who
      are unresponsive to corticosteroids and other immunosuppressive agents are at
      very high risk of progression to end stage kidney disease. In the absence of
      curative treatment, current therapy centers on renoprotective interventions that
      reduce proteinuria and fibrosis. The FONT (Novel Therapies for Resistant FSGS)
      Phase II clinical trial (NCT00814255, Registration date December 22, 2008) was
      designed to assess the efficacy of adalimumab and galactose compared to standard
      medical therapy which was comprised of lisinopril, losartan, and atorvastatin.
      METHODS: Key eligibility criteria were biopsy confirmed primary FSGS or
      documentation of a causative genetic mutation, urine protein:creatinine ratio
      >1.0 g/g, and estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m(2).
      The experimental treatments - adalimumab, galactose, standard medical therapy--
      were administered for 26 weeks. The primary endpoint was a 50 % reduction in
      proteinuria with stable eGFR. RESULTS: Thirty-two subjects were screened and 21
      were assigned to one of the three study arms. While none of the adalimumab
      treated subjects achieved the primary outcome, 2 subjects in the galactose and 2
      in the standard medical therapy arm had a 50 % reduction in proteinuria without a
      decline in eGFR. The proteinuria response did not correlate with serial changes
      in the serum glomerular permeability activity measured by the Palb assay or
      soluble urokinase plasminogen activator receptor (suPAR). There were no serious
      adverse effects related to treatments in the study. CONCLUSIONS: Recruitment into
      this trial that addressed patients with resistant FSGS fell short of the
      enrollment goal. Our findings suggest that future studies of novel therapies for
      rare glomerular diseases such as FSGS may benefit from enrollment of patients
      earlier in the course of their disease. In addition, better identification of
      patients who are likely to respond to a new treatment based on biomarkers
      suggesting involvement of the disease pathway targeted by the experimental agent
      may reduce the required sample size and increase the likelihood of a favorable
      outcome.

PMID- 26198844
TI  - Intrinsic hierarchical structural imperfections in a natural ceramic of bivalve
      shell with distinctly graded properties.
AB  - Despite the extensive investigation on the structure of natural biological
      materials, insufficient attention has been paid to the structural imperfections
      by which the mechanical properties of synthetic materials are dominated. In this
      study, the structure of bivalve Saxidomus purpuratus shell has been
      systematically characterized quantitatively on multiple length scales from
      millimeter to sub-nanometer. It is revealed that hierarchical imperfections are
      intrinsically involved in the crossed-lamellar structure of the shell despite its
      periodically packed platelets. In particular, various favorable characters which
      are always pursued in synthetic materials, e.g. nanotwins and low-angle
      misorientations, have been incorporated herein. The possible contributions of
      these imperfections to mechanical properties are further discussed. It is
      suggested that the imperfections may serve as structural adaptations, rather than
      detrimental defects in the real sense, to help improve the mechanical properties
      of natural biological materials. This study may aid in understanding the
      optimizing strategies of structure and properties designed by nature, and
      accordingly, provide inspiration for the design of synthetic materials. 

PMID- 26198846
TI  - Pliocene hominin biogeography and ecology.
AB  - Australopithecus bahrelghazali, its origin and palaeobiology are not well
      understood. Reported from only one location some several thousand kilometres away
      from East African Pliocene hominin sites, it appears to have predominantly fed on
      C4 sources. Yet, it lacks the morphological adaptations of other primate C4
      consumers like Paranthropus boisei and Theropithecus oswaldi. Furthermore,
      although considered to belong to Australopithecus afarensis by most researchers,
      A. bahrelghazali appears to differ from the former in a key aspect of its
      morphology: enamel thickness. To assess the phylogeny and palaeobiology of A.
      bahrelghazali, I first evaluate the dietary adaptations and energetics of A.
      bahrelghazali using empirical data of the feeding ecology of extant baboons,
      Papio cynocephalus. Information published on A. bahrelghazali morphology and
      habitat preference is used to select C4 foods with the appropriate mechanical
      properties and availability within the environment to create the models. By
      altering the feeding time on various food categories, I then test whether A.
      bahrelghazali could have subsisted on a C4 diet, thus accounting for the
      delta(13)C composition of its dental tissue. The effects of body mass on the
      volume of food consumed are taken into account. The outcomes of these simulations
      indicate that A. bahrelghazali could have subsisted on a diet of predominantly
      sedges, albeit with limitations. At higher energy requirements, i.e., above 3.5
      times the BMR, it would be difficult for a medium-sized primate to obtain
      sufficient energy from a sedge-based diet. This is apparently due to constraints
      on foraging/feeding time, not because of the nutritional value of sedges per se.
      These results are discussed against the backdrop of A. bahrelghazali
      biogeography, palaeoenvironment, and phylogeny. The combined evidence makes it
      plausible to suggest that Northern Chad may have been a refugium for migrating
      mammals, including hominins, and throws new light on the deep history of A.
      bahrelghazali.

PMID- 26198845
TI  - Bridge hosts, a missing link for disease ecology in multi-host systems.
AB  - In ecology, the grouping of species into functional groups has played a valuable
      role in simplifying ecological complexity. In epidemiology, further
      clarifications of epidemiological functions are needed: while host roles may be
      defined, they are often used loosely, partly because of a lack of clarity on the
      relationships between a host's function and its epidemiological role. Here we
      focus on the definition of bridge hosts and their epidemiological consequences.
      Bridge hosts provide a link through which pathogens can be transmitted from
      maintenance host populations or communities to receptive populations that people
      want to protect (i.e., target hosts). A bridge host should (1) be competent for
      the pathogen or able to mechanically transmit it; and (2) come into direct
      contact or share habitat with both maintenance and target populations.
      Demonstration of bridging requires an operational framework that integrates
      ecological and epidemiological approaches. We illustrate this framework using the
      example of the transmission of Avian Influenza Viruses across wild bird/poultry
      interfaces in Africa and discuss a range of other examples that demonstrate the
      usefulness of our definition for other multi-host systems. Bridge hosts can be
      particularly important for understanding and managing infectious disease dynamics
      in multi-host systems at wildlife/domestic/human interfaces, including emerging
      infections.

PMID- 26198847
TI  - Central nervous system granulomastous phlebitis with limited extracranial
      involvement of the heart and lungs: An autopsy case.
AB  - Primary angiitis of the central nervous system is a rare condition, usually with
      an insidious onset. There is a wide variety of histological types (granulomatous,
      lymphocytic or necrotizing vasculitis) and types of vessel involved (arteries,
      veins or both). Most cases are idiopathic. We describe a first case of idiopathic
      granulomatous central nervous system phlebitis with additional limited
      involvement of the heart and lung, exclusively affecting small and medium sized
      veins in a 22-year-old woman, presenting as a sub acute headache. The reasons for
      this peculiar limitation of inflammation to the veins and the involvement of the
      heart and lungs are unknown. 

PMID- 26198848
TI  - Cell-recycle batch process of Scheffersomyces stipitis and Saccharomyces
      cerevisiae co-culture for second generation bioethanol production.
AB  - OBJECTIVES: To achieve an optimized co-culture ratio of Scheffersomyces stipitis
      and Saccharomyces cerevisiae for the production of second generation bioethanol
      under a cell-recycle batch process. RESULTS: Three Sacc. cerevisiae strains were
      evaluated in co-culture with Sch. stipitis CBS 5773 at different ratios using
      synthetic medium containing glucose and xylose. Bioreactor trials indicated that
      the optimal condition for ethanol production using Sacc. cerevisiae EC1118 and
      Sch. stipitis co-culture was 1 % of O2 concentration. To increase ethanol
      production with Sacc. cerevisiae/Sch. stipitis co-culture a cell-recycle batch
      process was evaluated. Using this process, the maximum ethanol production (9.73 g
      l(-1)) and ethanol yield (0.42 g g(-1)) were achieved exhibiting a tenfold
      increase in ethanol productivity in comparison with batch process (2.1 g l(-1) h(
      1)). In these conditions a stabilization of the cells ratio Sacc. cerevisiae/Sch.
      stipitis (1:5) at steady state condition was obtained. CONCLUSION: Batch cells
      recycling fermentation is an effective process to use Sch. stipitis/Sacc.
      cerevisiae co-culture for second generation ethanol production.

PMID- 26198849
TI  - Improved properties of bone and cartilage tissue from 3D inkjet-bioprinted human
      mesenchymal stem cells by simultaneous deposition and photocrosslinking in PEG
      GelMA.
AB  - OBJECTIVES: Bioprinting of bone and cartilage suffers from low mechanical
      properties. Here we have developed a unique inkjet bioprinting approach of
      creating mechanically strong bone and cartilage tissue constructs using
      poly(ethylene glycol) dimethacrylate, gelatin methacrylate, and human MSCs.
      RESULTS: The printed hMSCs were evenly distributed in the polymerized PEG-GelMA
      scaffold during layer-by-layer assembly. The procedure showed a good
      biocompatibility with >80% of the cells surviving the printing process and the
      resulting constructs provided strong mechanical support to the embedded cells.
      The printed mesenchymal stem cells showed an excellent osteogenic and
      chondrogenic differentiation capacity. Both osteogenic and chondrogenic
      differentiation as determined by specific gene and protein expression analysis
      (RUNX2, SP7, DLX5, ALPL, Col1A1, IBSP, BGLAP, SPP1, Col10A1, MMP13, SOX9, Col2A1,
      ACAN) was improved by PEG-GelMA in comparison to PEG alone. These observations
      were consistent with the histological evaluation. CONCLUSIONS: Inkjet bioprinted
      hMSCs in simultaneously photocrosslinked PEG-GelMA hydrogel scaffolds
      demonstrated an improvement of mechanical properties and osteogenic and
      chondrogenic differentiation, suggesting its promising potential for usage in
      bone and cartilage tissue engineering.

PMID- 26198850
TI  - Cell death induction by the BH3 mimetic GX15-070 in thyroid carcinoma cells.
AB  - BACKGROUND: The evasion of cell death is one of the hallmarks of cancer,
      contributing to both tumor progression and resistance to therapy.
      Dedifferentiated and anaplastic thyroid carcinomas that do not take up
      radioiodine are resistant to conventional anticancer treatments and patients with
      these tumors are difficult to treat. BH3 mimetics are a new class of drugs that
      target anti-apoptotic proteins of the BCL-2 family and promote cell death. The
      purpose of this study was to analyze the molecular effects of the BH3 mimetic
      GX15-070 on thyroid carcinoma cell lines and to characterize cell death induced
      by GX15-070. METHODS: A total of 17 cell lines derived from follicular,
      papillary, and anaplastic thyroid carcinomas were treated with GX15-070. Cell
      viability was measured with MTT assay while cell cycle phase distribution and
      subG1 peaks were determined after propidium iodide staining. We assessed cell
      death via the caspase 3/7 activity, caspase cleavage products, lactate
      dehydrogenase (LDH) liberation assays, and a LC3 analysis by western blot.
      Ultrastructural changes were analysed by electron microscopy of GX15-070-treated
      cells. RESULTS: After GX15-070 treatment, the number of viable cells was
      decreased in all cell lines examined, with IC50 values ranging from 48nM to 3.25
      MUM. We observed biochemical markers of autophagic cell death and necrosis like
      LC3 conversion and LDH release after the GX15-070 treatment. Electron microscopy
      revealed several common characteristic ultrastructural changes like swelling of
      mitochondria, dilatation of rough endoplasmic reticulum, membrane blebbing and
      formation of vacuoles. GX15-070 treatment induced DNA fragmentation detected by
      subG1-peak induction and an arrest in G1 phase of the cell cycle. Caspase
      activation after GX15-070 incubation was detected but had no effect on viability
      of cells. CONCLUSIONS: With these experiments we demonstrated the efficacy of the
      BH3 mimetic drug GX15-070 acting against dedifferentiated thyroid carcinoma cells
      of various histological origins by the induction of cell death. GX15-070-treated
      cells underwent non-classical cell death with signs of apoptosis, autophagy and
      necrosis in parallel. GX15-07 and related compounds thus may be a new therapeutic
      option for dedifferentiated thyroid carcinoma of various histological subtypes.

PMID- 26198852
TI  - Self-doped Ti(3+)-TiO2 as a photocatalyst for the reduction of CO2 into a
      hydrocarbon fuel under visible light irradiation.
AB  - Self-doped TiO2 shows visible light photocatalytic activity, while commercial
      TiO2 (P25) is only UV responsive. The incorporation of Ti(3+) into TiO2
      structures narrows the band gap (2.90 eV), leading to significantly increased
      photocatalytic activity for the reduction of CO2 into a renewable hydrocarbon
      fuel (CH4) in the presence of water vapour under visible light irradiation. 

PMID- 26198851
TI  - The completed genome sequence of the pathogenic ascomycete fungus Fusarium
      graminearum.
AB  - BACKGROUND: Accurate genome assembly and gene model annotation are critical for
      comparative species and gene functional analyses. Here we present the completed
      genome sequence and annotation of the reference strain PH-1 of Fusarium
      graminearum, the causal agent of head scab disease of small grain cereals which
      threatens global food security. Completion was achieved by combining (a) the
      BROAD Sanger sequenced draft, with (b) the gene predictions from Munich
      Information Services for Protein Sequences (MIPS) v3.2, with (c) de novo whole
      genome shotgun re-sequencing, (d) re-annotation of the gene models using RNA-seq
      evidence and Fgenesh, Snap, GeneMark and Augustus prediction algorithms, followed
      by (e) manual curation. RESULTS: We have comprehensively completed the genomic
      36,563,796 bp sequence by replacing unknown bases, placing supercontigs within
      their correct loci, correcting assembly errors, and inserting new sequences which
      include for the first time complete AT rich sequences such as centromere
      sequences, subtelomeric regions and the telomeres. Each of the four F.
      graminearium chromosomes was found to be submetacentric with respect to
      centromere positioning. The position of a potential neocentromere was also
      defined. A preferentially higher frequency of genetic recombination was observed
      at the end of the longer arm of each chromosome. Within the genome 1529 gene
      models have been modified and 412 new gene models predicted, with a total gene
      call of 14,164. The re-annotation impacts upon 69 entries held within the
      Pathogen-Host Interactions database (PHI-base) which stores information on genes
      for which mutant phenotypes in pathogen-host interactions have been
      experimentally tested, of which 59 are putative transcription factors, 8 kinases,
      1 ATP citrate lyase (ACL1), and 1 syntaxin-like SNARE gene (GzSYN1). Although the
      completed F. graminearum contains very few transposon sequences, a previously
      unrecognised and potentially active gypsy-type long-terminal-repeat (LTR)
      retrotransposon was identified. In addition, each of the sub-telomeres and
      centromeres contained either a LTR or MarCry-1_FO element. The full content of
      the proposed ancient chromosome fusion sites has also been revealed and
      investigated. Regions with high recombination previously noted to be rich in
      secretome encoding genes were also found to be rich in tRNA sequences. This study
      has identified 741 F. graminearum species specific genes and provides the first
      complete genome assembly for a Sordariomycetes species. CONCLUSIONS: This fully
      completed F. graminearum PH-1 genome and manually curated annotation, available
      at Ensembl Fungi, provides the optimum resource to perform interspecies
      comparative analyses and gene function studies.

PMID- 26198853
TI  - Identification and characterization of SMU.244 encoding a putative undecaprenyl
      pyrophosphate phosphatase protein required for cell wall biosynthesis and
      bacitracin resistance in Streptococcus mutans.
AB  - Streptococcus mutans in dental biofilms often faces life-threatening threats such
      as killing by antimicrobial molecules from competing species or from the host.
      The ability of S. mutans to cope with such threats is crucial for its survival
      and persistence in dental biofilms. By screening a transposon mutant library, we
      identified 11 transposon insertion mutants that were sensitive to bacitracin. Two
      of these mutants, XTn-01 and XTn-03, had an independent insertion in the same
      locus, SMU.244, which encoded a homologue of undecaprenyl pyrophosphate
      phosphatase (UppP). In this study, we describe the genetic and phenotypic
      characterization of SMU.244 in antibiotic resistance. The results revealed that
      deletion of SMU.244 results in a mutant (XTDelta244) that is highly sensitive to
      bacitracin, but confers more resistance to lactococcin G, a class IIb
      bacteriocin. Introduction of the intact SMU.244 into XTDelta244 in trans
      completely restores its resistance to bacitracin and the susceptibility to
      lactococcin G. The XTDelta244 was also defective in forming the WT biofilm,
      although its growth was not significantly affected. Using recombinant protein
      technology, we demonstrated that the SMU.244-encoded protein displays enzyme
      activity to catalyse dephosphorylation of the substrate. The lux transcriptional
      reporter assays showed that S. mutans maintains a moderate level of expression of
      SMU.244 in the absence of bacitracin, but bacitracin at sub-MICs can further
      induce its expression. We concluded that SMU.244 encodes an UppP protein that
      plays important roles in cell wall biosynthesis and bacitracin resistance in S.
      mutans. The results described here may further our understanding of the molecular
      mechanisms by which S. mutans copes with antibiotics such as bacitracin. 

PMID- 26198854
TI  - Dietary therapy is not the best option for refractory nonsurgical epilepsy.
AB  - The ketogenic diet (KD) is currently a well-established treatment for patients
      with medically refractory, nonsurgical epilepsy. However, despite its efficacy,
      the KD is highly restrictive and constitutes a treatment with serious potential
      adverse effects, and often with difficulties in its implementation and
      compliance. Patients on the KD require strict follow-up and constant supervision
      by a medical team highly experienced in its management in order to prevent
      complications. Other alternative treatments for patients with refractory epilepsy
      include vagus nerve stimulation (VNS), new-generation antiepileptic drugs (AEDs),
      corpus callosotomy (CC), and responsive focal cortical stimulation (RNS). In this
      review, we explain not only the difficulties of the KD as a therapeutic option
      for refractory epilepsy but also the benefits of other therapeutic strategies,
      which, in many cases, have proven to have better efficacy than the KD itself. 

PMID- 26198855
TI  - Effectiveness of the Comprehensive Approach to Rehabilitation (CARe) methodology:
      design of a cluster randomized controlled trial.
AB  - BACKGROUND: There is an increasing amount of evidence for the effectiveness of
      rehabilitation interventions for people with severe mental illness (SMI). In the
      Netherlands, a rehabilitation methodology that is well known and often applied is
      the Comprehensive Approach to Rehabilitation (CARe) methodology. The overall goal
      of the CARe methodology is to improve the client's quality of life by supporting
      the client in realizing his/her goals and wishes, handling his/her vulnerability
      and improving the quality of his/her social environment. The methodology is
      strongly influenced by the concept of 'personal recovery' and the 'strengths case
      management model'. No controlled effect studies have been conducted hitherto
      regarding the CARe methodology. METHODS/DESIGN: This study is a two-armed cluster
      randomized controlled trial (RCT) that will be executed in teams from three
      organizations for sheltered and supported housing, which provide services to
      people with long-term severe mental illness. Teams in the intervention group will
      receive the multiple-day CARe methodology training from a specialized institute
      and start working according the CARe Methodology guideline. Teams in the control
      group will continue working in their usual way. Standardized questionnaires will
      be completed at baseline (T0), and 10 (T1) and 20 months (T2) post baseline.
      Primary outcomes are recovery, social functioning and quality of life. The model
      fidelity of the CARe methodology will be assessed at T1 and T2. DISCUSSION: This
      study is the first controlled effect study on the CARe methodology and one of the
      few RCTs on a broad rehabilitation method or strength-based approach. This study
      is relevant because mental health care organizations have become increasingly
      interested in recovery and rehabilitation-oriented care. TRIAL REGISTRATION: The
      trial registration number is ISRCTN77355880 .

PMID- 26198856
TI  - Anti-platelet factor 4/heparin antibody is associated with progression of
      peripheral arterial disease in hemodialysis patients.
AB  - BACKGROUND: Heparin therapy may induce anti-platelet factor 4/heparin antibody
      (PF4-H Ab). Hemodialysis patients receive scheduled heparin and are at a risk of
      developing PF4-H Ab. Hemodialysis patients are also at a high risk of peripheral
      arterial disease (PAD). This study examines whether chronic PF4-H Ab exposure
      contributes to the progression of PAD measured by ankle brachial index (ABI) in
      hemodialysis patients. MATERIALS AND METHODS: A total of 71 hemodialysis patients
      were enrolled, and the association between clinical, biochemical parameters and
      ABI after 3 years was studied. PF4-H Ab was evaluated by ELISA, and patients with
      titer >= 0.4 were taken as having PF4-H Ab. RESULTS: Mean ABI was 1.04 +/- 0.18
      at baseline and 1.01 +/- 0.17 after 3 years. Mean DeltaABI (change in ABI after 3
      years) was -0.04 +/- 0.13. PF4-H Ab was positive in 26 patients. PF4-H Ab was not
      related to hemodialysis duration, DM history, smoking and age. Platelet count
      showed no correlation with PF4-H Ab. However, there was significance in DeltaABI
      between PF4-H Ab-positive and PF4-H Ab-negative patients (p = 0.002). DeltaABI
      was negatively correlated with PF4-H Ab and 3-year averaged serum Ca * P only
      (beta = -0.378, p = 0.001; beta = -0.263, p = 0.018, respectively). However, in
      PF4-H Ab-positive patients, the extent of DeltaABI did not correlate with PF4-H
      Ab titers (r = -0.021, p = 0.921). CONCLUSIONS: PF4-H Ab positivity, along with
      high levels of serum Ca * P, played a potential role in the progression of PAD
      over time.

PMID- 26198857
TI  - Analysis of Short-Term Cortisol Stress Response in Channel Catfish by
      Anesthetization with Metomidate Hydrochloride and Tricaine Methanesulfonate.
AB  - The ability of the anesthetics metomidate hydrochloride and tricaine
      methanesulfonate (MS-222) to mitigate the cortisol stress response of Channel
      Catfish Ictalurus punctatus was evaluated during a 10-min confinement stress. The
      cortisol concentrations of Channel Catfish anesthetized in metomidate
      hydrochloride remained consistent throughout the 10-min exposure; however, for
      fish anesthetized with MS-222 and nonanesthetized fish, cortisol concentrations
      were approximately 7- and 22-fold higher, respectively, than the baseline
      concentrations. While both anesthetics reduced cortisol concentrations relative
      to those of nonanesthetized fish, these results suggest that MS-222 is an
      appropriate anesthetic to use during the initial 5 min of sedation and that
      metomidate hydrochloride is appropriate for longer periods of sedation.

PMID- 26198858
TI  - Chronic venous ulcer treatment with topical sevoflurane.

PMID- 26198860
TI  - Plain Language Summary: Adult Sinusitis (Sinus Infection).
AB  - OBJECTIVE: This plain language summary serves as an overview in explaining
      sinusitis (pronounced sign-you-side-tis). The purpose of this plain language
      summary is to provide patients with standard language explaining their condition
      in an easy-to-read format. This summary applies to those 18 years of age or older
      with sinusitis. The summary is featured as an FAQ (frequently asked question)
      format. The summary addresses how to manage and treat sinusitis symptoms. Adult
      sinusitis is often called a sinus infection. A healthcare provider may refer to a
      sinus infection as rhinosinusitis (pronounced rhi-no-sign-you-side-tis). This
      includes the nose as well as the sinuses in the name. A sinus infection is the
      swelling of the sinuses and nasal cavity.The summary is based on the published
      2015 "Clinical Practice Guideline: Adult Sinusitis." The evidence-based guideline
      includes research to support more effective diagnosis and treatment of adult
      sinus infections. The guideline was developed as a quality improvement
      opportunity for managing sinus infections by creating clear recommendations to
      use in medical practice.

PMID- 26198861
TI  - Letter to the Editor on "Simulating the Nasal Cycle with Computational Fluid
      Dynamics".

PMID- 26198862
TI  - Response to Dr Chung's Question on Simulating the Nasal Cycle with Computational
      Fluid Dynamics.

PMID- 26198863
TI  - Corrigendum.

PMID- 26198864
TI  - The inaccuracy of using landmark techniques for cricothyroid membrane
      identification: a comparison of three techniques.
AB  - OBJECTIVES: Successful cricothyrotomy is predicated on accurate identification of
      the cricothyroid membrane (CTM) by palpation of superficial anatomy. However,
      recent research has indicated that accuracy of the identification of the CTM can
      be as low as 30%, even in the hands of skilled providers. To date, there are very
      little data to suggest how to best identify this critical landmark. The objective
      was to compare three different methods of identifying the CTM. METHODS: A
      convenience sample of patients and physician volunteers who met inclusion
      criteria was consented. The patients were assessed by physician volunteers who
      were randomized to one of three methods for identifying the CTM (general
      palpation of landmarks vs. an approximation based on four finger widths vs. an
      estimation based on overlying skin creases of the neck). Volunteers would then
      mark the skin with an invisible but florescent pen. A single expert evaluator
      used ultrasound to identify the superior and inferior borders of the CTM. The
      variably colored florescent marks were then visualized with ultraviolet light and
      the accuracy of the various methods was recorded as the primary outcome.
      Additionally, the time it took to perform each technique was measured.
      Descriptive statistics and report 95% confidence intervals (CIs) are reported.
      RESULTS: Fifty adult patients were enrolled, 52% were female, and mean body mass
      index was 28 kg/m(2) (95% CI = 26 to 29 kg/m(2) ). The general palpation method
      was successful 62% of the time (95% CI = 48% to 76%) and took an average of 14
      seconds to perform (range = 5 to 45 seconds). In contrast, the four-finger
      technique was successful 46% of the time (95% CI = 32% to 60%) and took an
      average of 12 seconds to perform (range = 6 to 40 seconds). Finally, the neck
      crease method was successful 50% of the time (95% CI = 36% to 64%) and took an
      average of 11 seconds to perform (range = 5 to 15 seconds). CONCLUSIONS: All
      three methods performed poorly overall. All three techniques might potentially be
      even less accurate in instances where the superficial anatomy is not palpable due
      to body habitus. These findings should alert clinicians to the significant risk
      of a misplaced cricothyrotomy and highlight the critical need for future
      research.

PMID- 26198865
TI  - Isolation and quantitation of Clostridium difficile in aqueous and fecal matter
      using two types of selective media.
AB  - We evaluated the isolation and quantitation of Clostridium difficile from aqueous
      and fecal samples utilizing ChromID CDIF and cycloserine, cefoxitin, and fructose
      containing agar with horse blood and taurocholate media. Growth was similar
      between the two. ChromID CDIF provided enhanced isolation and required no ethanol
      pretreatment to inhibit normal flora. ChromID CDIF also improved turn-around
      time, requiring only 24 hours' incubation. 

PMID- 26198866
TI  - Characterization of a Rh(III) porphyrin-CO complex: its structure and reactivity
      with an electron acceptor.
AB  - To analyse the electrocatalytic oxidation of carbon monoxide by Rh porphyrins, we
      isolated a CO-adduct of Rh octaethylporphyrin, and examined its properties and
      reactivity by IR, NMR, and X-ray crystallographic analyses. The results indicate
      that the CO adduct of Rh octaethylporphyrin is vulnerable to nucleophilic attack
      by H2O. The CO-adduct was easily oxidized by an electron acceptor (1,4
      naphthoquinone) to generate CO2. This indicates that CO is sufficiently activated
      in the CO complex of Rh octaethylporphyrin to reduce an electron acceptor. This
      mechanism is in contrast to that for the CO oxidation by Pt-based
      electrocatalysts. 

PMID- 26198867
TI  - Interdependent TTF1 - ErbB4 interactions are critical for surfactant protein-B
      homeostasis in primary mouse lung alveolar type II cells.
AB  - ErbB4 receptor and thyroid transcription factor (TTF)-1 are important modulators
      of fetal alveolar type II (ATII) cell development and injury. ErbB4 is an
      upstream regulator of TTF-1, promoting its expression in MLE-12 cells, an ATII
      cell line. Both proteins are known to promote surfactant protein-B gene (SftpB)
      and protein (SP-B) expression, but their feedback interactions on each other are
      not known. We hypothesized that TTF-1 expression has a feedback effect on ErbB4
      expression in an in-vitro model of isolated mouse ATII cells. We tested this
      hypothesis by analyzing the effects of overexpressing HER4 and Nkx2.1, the genes
      of ErbB4 and TTF-1 on TTF-1 and ErbB4 protein expression, respectively, as well
      as SP-B protein expression in primary fetal mouse lung ATII cells. Transient
      ErbB4 protein overexpression upregulated TTF-1 protein expression in primary
      fetal ATII cells, similarly to results previously shown in MLE-12 cells.
      Transient TTF-1 protein overexpression down regulated ErbB4 protein expression in
      both cell types. TTF-1 protein was upregulated in primary transgenic ErbB4
      depleted adult ATII cells, however SP-B protein expression in these adult
      transgenic ATII cells was not affected by the absence of ErbB4. The observation
      that TTF-1 is upregulated in fetal ATII cells by ErbB4 overexpression and also in
      ErbB4-deleted adult ATII cells suggests additional factors interact with ErbB4 to
      regulate TTF-1 levels. We conclude that the interdependency of TTF-1 and ErbB4 is
      important for surfactant protein levels. The interactive regulation of ErbB4 and
      TTF-1 needs further elucidation. 

PMID- 26198869
TI  - Preparation of Mealybugs (Hemiptera: Pseudococcidae) for Genetic Characterization
      and Morphological Examination.
AB  - Mealybugs (Hemiptera: Pseudococcidae) are economically significant agricultural
      pests on many different crops. Because of their small size and lack of easily
      visible characters for identification, determination of their taxonomic status is
      difficult and requires technical competency to prepare a slide-mounted specimen.
      The standard mounting technique does not allow for analysis of the genome of the
      specimen. Conversely, preparatory techniques for genetic analysis of mealybugs
      cause either loss of the entire individual or physical damage that can make
      morphology-based identification difficult. This study describes a simple protocol
      that does not impact physical integrity of the specimen for fixation and
      microscopic examination yet enables simultaneous DNA extraction for DNA-based
      identification of four mealybug species. All species prepared yielded high
      quality slide mounts, identified as Planococcus citri Risso, Pseudococcus viburni
      Signoret, Rhizoecus kondonis Kuwana, or Rhizoecus californicus Ferris. DNA
      extracted in this manner had higher purity and yield in the final eluate than in
      samples extracted using standard methods. DNA extracted was successfully
      amplified by polymerase chain reaction using primers for the cytochrome oxidase I
      gene and subsequently sequenced for all specimens. This protocol is likely to be
      applicable to other Hemiptera taxa that are preserved by slide mounting, allowing
      for both the preparation of a high-quality voucher specimen for morphological
      identification and simultaneous analysis of DNA for the same specimen. The
      methods used are technically less challenging than current standard procedures. 

PMID- 26198868
TI  - Identification of Putative Carboxylesterase and Glutathione S-transferase Genes
      from the Antennae of the Chilo suppressalis (Lepidoptera: Pyralidae).
AB  - In insects, rapid degradation of odorants in antennae is extremely important for
      the sensitivity of olfactory receptor neurons. Odorant degradation in insect
      antennae is mediated by multiple enzymes, especially the carboxylesterases (CXEs)
      and glutathione S-transferases (GSTs). The Asiatic rice borer, Chilo
      suppressalis, is an economically important lepidopteran pest which causes great
      economic damage to cultivated rice crops in many Asian countries. In this study,
      we identified 19 putative CXE and 16 GST genes by analyzing previously
      constructed antennal transcriptomes of C. suppressalis. BLASTX best hit results
      showed that these genes are most homologous to their respective orthologs in
      other lepidopteran species. Phylogenetic analyses revealed that these CXE and GST
      genes were clustered into various clades. Reverse-transcription quantitative
      polymerase chain reaction assays showed that three CXE genes (CsupCXE8,
      CsupCXE13, and CsupCXE18) are antennae-enriched. These genes are candidates for
      involvement in odorant degradation. Unexpectedly, none of the GST genes were
      found to be antennae-specific. Our results pave the way for future researches of
      the odorant degradation mechanism of C. suppressalis at the molecular level. 

PMID- 26198870
TI  - Morphological and DNA Barcoding Evidence for Invasive Pest Thrips, Thrips
      parvispinus (Thripidae: Thysanoptera), Newly Recorded From India.
AB  - South East Asia pest thrips species, Thrips parvispinus (Karny), is a serious
      pest on a number of agricultural and horticultural crops in a number of plant
      families. Based on an integrated approach of morphology and DNA barcoding,
      invasion of this serious pest is reported first time from India on papaya
      plantations. Molecular data have corroborated with the morphological
      identification. Haplotyping data suggested that the Indonesia may be a probable
      source of invasion of this pest to India. 

PMID- 26198871
TI  - Calcium Spikes in Epithelium: study on Drosophila early embryos.
AB  - Calcium ion acts in nearly every aspect of cellular life. The versatility and
      specificity required for such a ubiquitous role is ensured by the spatio-temporal
      dynamics of calcium concentration variations. While calcium signal dynamics has
      been extensively studied in cell cultures and adult tissues, little is known
      about calcium activity during early tissue morphogenesis. We monitored
      intracellular calcium concentration in Drosophila gastrula and revealed single
      cell calcium spikes that were short-lived, rare and showed strong variability
      among embryos. We quantitatively described the spatio-temporal dynamics of these
      spikes and analyzed their potential origins and nature by introducing physical
      and chemical perturbations. Our data highlight the inter- and intra-tissue
      variability of calcium activity during tissue morphogenesis. 

PMID- 26198873
TI  - A time to amaze, a time to settle down, and a time to discover.

PMID- 26198872
TI  - [Comments on the second Spanish version of the STOPP-START criteria: Reply].

PMID- 26198874
TI  - Expression of circulating microRNAs in patients with ST segment elevation acute
      myocardial infarction.
AB  - AIM: The aim of this study was to investigate microRNA expression in ST segment
      elevation myocardial infarction (STEMI) and non-ST segment elevation myocardial
      infarction (NSTEMI), and compare their diagnostic values. METHODS: We assessed 77
      STEMI and 21 NSTEMI patients admitted to the Department of Cardiology in Nanjing
      First Hospital from October 2013 to August 2014, and 23 healthy volunteers were
      selected at the same time. Serum miR-133a, miR-133b and miR-499-5p were measured
      by using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR),
      and the concentration of serum cTnI was measured by enzyme-linked immunosorbent
      assay (ELISA) methods. RESULTS: The level of miR-133a, miR-133b and miR-499-5p
      were significantly higher in both STEMI and NSTEMI patients compared to healthy
      volunteers (P<0.05), and were also considerably increased in the early phase (the
      first 4 hours) (P<0.05). CONCLUSION: Serum miR-133a, miR-133b and miR-499-5p can
      be used as a biomarker for early diagnosis of acute myocardial infarction (AMI).

PMID- 26198875
TI  - Symetis ACURATE TAVI: review of the technology, developments and current data
      with this self-expanding transcatheter heart valve.
AB  - The Symetis ACURATE TA and ACURATE neo technology is a novel transcatheter heart
      valve for treatment of aortic valvular stenosis. This review illustrates the
      implantation steps, which are designed for an easy and intuitive transapical and
      transfemoral TAVI procedure. The most important difference to other self
      expanding platforms is the top-down deployment with minimal protrusion of the
      stent towards the left ventricular outflow tract. In addition, the supra
      annularly placed porcine leaflets provide very low gradients and the pericardial
      skirt acts very effectively to seal against paravalvular leaks. This review
      reports about the hemodynamic features, low rates of paravalvular leaks and very
      low rates of pacemaker implantation, which have been observed in various
      registries. Meanwhile more than 3000 patients have been treated worldwide and
      additional registries are currently under investigation. 

PMID- 26198876
TI  - [AA-type amyloidosis secondary to multidrug resistant pulmonary tuberculosis:
      implications for therapy].
AB  - Multidrug resistant pulmonary tuberculosis was diagnosed to a 32-year-old man. An
      AA-amyloidosis was subsequently diagnosed on the renal biopsy performed for
      nephrotic syndrome and macroscopic hematuria. A 6-drug antibiotic treatment was
      delivered quickly after first results of genotypic antibiogram given the renal
      failure, and was secondarily adapted to the phenotypic antibiogram. Multidrug
      therapy was fairly well tolerated. Clinical and biological improving were slow.
      Although tuberculosis is a classic cause of amyloidosis, this is the first case
      reporting an association between a multidrug resistant case and an amyloidosis in
      adults. This case also raises the question of MDR probabilistic treatments in
      situations whether a vital organ prognosis is engaged.

PMID- 26198878
TI  - Polystyrene sphere-mediated ultrathin graphene sheet-assembled frameworks for
      high-power density Li-O2 batteries.
AB  - Free-standing, polystyrene sphere-mediated ultrathin graphene sheet-assembled
      aerogels (PGA) with open and interconnected porous frameworks were configured,
      exhibiting high energy density and high power density as a binder-free cathode
      for Li-O2 batteries. 

PMID- 26198879
TI  - MRI in the Diagnosis and Monitoring of Multiple Sclerosis: An Update.
AB  - Magnetic resonance imaging (MRI) is the most powerful tool for the early
      (differential) diagnosis of multiple sclerosis (MS) and has been part of the
      International Panel criteria (2001, 2005, 2010) for more than 10 years. The role
      of brain and spinal cord MRI in the diagnosis of MS is well established. New MR
      techniques and markers will further improve the diagnostic value in a research
      and clinical routine setting. In addition to diagnosis, MRI is widely used for
      prognostic evaluation as well as treatment efficacy and safety monitoring. This
      field has gained importance with the introduction of new MS therapeutics.
      Therefore, the scope of MRI-guided MS disease monitoring has been widened to
      include rigorous treatment monitoring aiming at "no evidence of disease activity
      (NEDA)". Next, safety monitoring of treated MS patients has become major concern
      to enable early detection of opportunistic infections such as progressive
      multifocal leukoencephalopathy (PML). Driven by these new developments, recently
      published expert panel guidelines stressed the need for standardized imaging
      protocols and targeted specialized imaging markers for MS diagnosis and disease
      monitoring. This review article aims to give an update on the role of MRI in the
      diagnosis and monitoring of MS with particular emphasis to treatment efficacy and
      safety, both in clinical practice and in research. 

PMID- 26198880
TI  - Quantitative Susceptibility Mapping: Concepts and Applications.
AB  - PURPOSE: To review the fundamental principles of susceptibility-weighted imaging
      (SWI) and quantitative susceptibility mapping (QSM), and to discuss recent
      clinical developments. METHODS: SWI is a magnetic resonance imaging method that
      takes advantage of magnitude signal loss and phase information to reveal anatomic
      and physiologic information about tissue and venous vasculature. The method
      enhances image contrast qualitatively, relying on phase shifts due to differences
      in magnetic susceptibility between tissues. QSM, extending SWI in an elegant way,
      is a new sophisticated postprocessing technique that numerically solves the
      inverse source-effect problem to derive local tissue magnetic susceptibility
      (source) from the measured magnetic field distribution (effect) as it is
      reflected in the phase images of gradient-echo sequences. RESULTS: SWI has
      meanwhile been established in numerous clinical as well as basic biomedical
      applications due to its ability to highlight tissue structures and compounds that
      are difficult to detect by conventional magnetic resonance imaging (MRI),
      including iron, calcifications, small veins, blood, and bones. The field of QSM
      has also progressed rapidly, both in terms of optimizing the post-processing
      strategies and algorithms as well as in gaining ground for new clinical
      applications that take advantage of its quantitative nature and improved
      specificity to identify the magnetic signature of lesions. CONCLUSIONS: Though
      magnetic susceptibility may be a major nuisance producing image artifacts in MRI,
      recent work has transformed it into a useful source of image contrast. Both SWI
      and QSM are gaining increasing acceptance in clinical practice. In particular,
      QSM provides new insights into tissue composition and organization due to its
      more direct relation to the actual physical tissue magnetic properties.

PMID- 26198881
TI  - Macroscopic modeling of mammalian cell growth and metabolism.
AB  - We review major modeling strategies and methods to understand and simulate the
      macroscopic behavior of mammalian cells. These strategies comprise two important
      steps: the first step is to identify stoichiometric relationships for the
      cultured cells connecting the extracellular inputs and outputs. In a second step,
      macroscopic kinetic models are introduced. These relationships together with
      bioreactor and metabolite balances provide a complete description of a system in
      the form of a set of differential equations. These can be used for the simulation
      of cell culture performance and further for optimization of production. 

PMID- 26198882
TI  - Selective production of rubusoside from stevioside by using the sophorose
      activity of beta-glucosidase from Streptomyces sp. GXT6.
AB  - In order to produce rubusoside, enzymes with preferential specificity for the
      saccharide sophorose were tested for ability to produce rubusoside from
      stevioside. We identified BGL1, a beta-glucosidase from Streptomyces sp. GXT6, as
      an enzyme for rubusoside production. Out of several saccharide substrates, BGL1
      showed the most affinity to sophorose. This enzyme only hydrolyzes the glucose
      moiety of the sophoroside at C-13 in stevioside. Production of rubusoside was
      determined by (1)H and (13)C nuclear magnetic resonance (NMR). Thus, rubusoside
      was produced from stevioside and the stevioside conversion rate was 98.2 %. The
      production yield of rubusoside was 78.8 % in 6 h.

PMID- 26198883
TI  - Antiviral activities of whey proteins.
AB  - Milk contains an array of proteins with useful bioactivities. Many milk proteins
      encompassing native or chemically modified casein, lactoferrin, alpha
      lactalbumin, and beta-lactoglobulin demonstrated antiviral activities. Casein and
      alpha-lactalbumin gained anti-HIV activity after modification with 3
      hydroxyphthalic anhydride. Many milk proteins inhibited HIV reverse
      transcriptase. Bovine glycolactin, angiogenin-1, lactogenin, casein, alpha
      lactalbumin, beta-lactoglobulin, bovine lactoferrampin, and human lactoferrampin
      inhibited HIV-1 protease and integrase. Several mammalian lactoferrins prevented
      hepatitis C infection. Lactoferrin, methylated alpha-lactalbumin and methylated
      beta-lactoglobulin inhibited human cytomegalovirus. Chemically modified alpha
      lactalbumin, beta-lactoglobulin and lysozyme, lactoferrin and lactoferricin,
      methylated alpha-lactalbumin, methylated and ethylated beta-lactoglobulins
      inhibited HSV. Chemically modified bovine beta-lactoglobulin had antihuman
      papillomavirus activity. Beta-lactoglobulin, lactoferrin, esterified beta
      lactoglobulin, and esterified lactoferrindisplayed anti-avian influenza A (H5N1)
      activity. Lactoferrin inhibited respiratory syncytial virus, hepatitis B virus,
      adenovirus, poliovirus, hantavirus, sindbis virus, semliki forest virus,
      echovirus, and enterovirus. Milk mucin, apolactoferrin, Fe(3+)-lactoferrin, beta
      lactoglobulin, human lactadherin, bovine IgG, and bovine kappa-casein
      demonstrated antihuman rotavirus activity. 

PMID- 26198884
TI  - Quantifying the broader economic consequences of quadrivalent human
      papillomavirus (HPV) vaccination in Germany applying a government perspective
      framework.
AB  - HPV infections can cause substantial burden in females and males as it is
      associated with several genital cancers, in addition to genital warts.
      Traditional economic evaluations often focus on quantifying cost-effectiveness,
      however, it is increasingly recognized that vaccinations may generate broader
      benefits not captured in cost-effectiveness analysis. Tauhe aim of this study was
      to evaluate the broader economic consequences associated with HPV vaccination in
      males and females and to conduct a lifetime cost-benefit analysis of investing in
      universal vaccination in Germany from the perspective of government.
      Methodologies from generational accounting, human capital and health economics
      were combined to estimate the broader economic consequences of HPV vaccination
      including the fiscal impact for the government. A cohort model was developed
      simulating the medical costs and average lifetime fiscal transfers between the
      government and 12-year-old immunized and non-immunized males and females. To
      estimate tax revenue attributed to vaccination-related changes in morbidity and
      mortality, direct and indirect tax rates were linked to differences in age- and
      gender-specific earnings. Based on HPV vaccination costs, the base case cost
      benefit analysis demonstrated that investing <euro>1 in universal HPV vaccination
      could yield <euro>1.7 in gross tax revenue over the lifetime of the cohorts.
      After taking into consideration the governmental transfers, universal HPV
      vaccination in Germany could result in incremental positive net discounted taxes
      (i.e. tax revenue-transfers) from <euro>62 million for the German government. The
      vaccination of males and females with the quadrivalent HPV vaccine is likely to
      have positive effects on public finances. 

PMID- 26198885
TI  - Photo-induced toxicity of Deepwater Horizon slick oil to blue crab (Callinectes
      sapidus) larvae.
AB  - The 2010 Deepwater Horizon oil spill resulted in the accidental release of
      approximately 700 million L of crude oil into the Gulf of Mexico. Photo-induced
      toxicity after co-exposure to ultraviolet (UV) radiation is 1 mechanism by which
      polycyclic aromatic hydrocarbons (PAHs) from oil spills may exert toxicity. Blue
      crab are an important commercial and ecological resource in the Gulf of Mexico,
      and their largely transparent larvae may make them sensitive to PAH photo-induced
      toxicity. The goal of the present study was to examine the sensitivity of early
      lifestage blue crab (Callinectes sapidus) zoea to slick oil collected during the
      Deepwater Horizon spill. Blue crab zoea were exposed to 1 of several dilutions of
      water accommodated fractions from 1 of 2 sources of oil and gradations of natural
      sunlight in a factorial design. Two 7-h solar exposures were carried out with a
      recovery period (dark) in between. Survival was found to be UV- and PAH
      dependent. Toxicity was observed within the range of surface PAH concentrations
      reported in the Gulf of Mexico during the Deepwater Horizon spill. These findings
      indicate that early lifestage blue crab are sensitive to photo-induced toxicity
      from Deepwater Horizon slick oil.

PMID- 26198886
TI  - iSBatch: a batch-processing platform for data analysis and exploration of live
      cell single-molecule microscopy images and other hierarchical datasets.
AB  - Recent technical advances have made it possible to visualize single molecules
      inside live cells. Microscopes with single-molecule sensitivity enable the
      imaging of low-abundance proteins, allowing for a quantitative characterization
      of molecular properties. Such data sets contain information on a wide spectrum of
      important molecular properties, with different aspects highlighted in different
      imaging strategies. The time-lapsed acquisition of images provides information on
      protein dynamics over long time scales, giving insight into expression dynamics
      and localization properties. Rapid burst imaging reveals properties of individual
      molecules in real-time, informing on their diffusion characteristics, binding
      dynamics and stoichiometries within complexes. This richness of information,
      however, adds significant complexity to analysis protocols. In general, large
      datasets of images must be collected and processed in order to produce
      statistically robust results and identify rare events. More importantly, as live
      cell single-molecule measurements remain on the cutting edge of imaging, few
      protocols for analysis have been established and thus analysis strategies often
      need to be explored for each individual scenario. Existing analysis packages are
      geared towards either single-cell imaging data or in vitro single-molecule data
      and typically operate with highly specific algorithms developed for particular
      situations. Our tool, iSBatch, instead allows users to exploit the inherent
      flexibility of the popular open-source package ImageJ, providing a hierarchical
      framework in which existing plugins or custom macros may be executed over entire
      datasets or portions thereof. This strategy affords users freedom to explore new
      analysis protocols within large imaging datasets, while maintaining hierarchical
      relationships between experiments, samples, fields of view, cells, and individual
      molecules. 

PMID- 26198887
TI  - Application of "Omics" Technologies for Diagnosis and Pathogenesis of
      Neurological Infections.
AB  - Infections of the human nervous system have substantial morbidity and mortality
      but also represent among the most challenging of all neurological diseases
      because of the difficulty in establishing a diagnosis and implementing effective
      therapies. Neurological infections lead to altered expression levels of a wide
      range of host- and pathogen-derived biomolecules both within and outside of the
      nervous system. Quantitative analyses of these biomolecular perturbations have
      been traditionally performed using "classical" molecular or analytical methods,
      which evaluate one or few genes or their products at a time. Recent technical
      developments together with the increasing availability of high-throughput/content
      methodologies have enabled a more comprehensive overview of these molecular
      alterations and thus provide new approaches to the diagnosis and/or treatment of
      this group of disorders. Herein, we will review recent evidence pointing to the
      capacity of the so-called omics techniques in studying the nervous system
      infections with an emphasis on genomics, transcriptomics, and proteomics
      technologies. 

PMID- 26198888
TI  - Cognitive Profile of C9orf72 in Frontotemporal Dementia and Amyotrophic Lateral
      Sclerosis.
AB  - This review article focuses on the cognitive profile associated with the C9orf72
      gene with GGGGCC (G4C2) hexanucleotide repeat expansions that is commonly found
      in both familial and sporadic forms of frontotemporal dementia (FTD) and
      amyotrophic lateral sclerosis (ALS) in order to aid clinicians in the screening
      process. In this growing clinical continuum between FTD and ALS, understanding
      and recognizing a neurocognitive profile is important for diagnosis. Key features
      of this profile include executive dysfunction with memory impairment and language
      deficits as the disease progresses. Behaviorally, patients are prone to
      disinhibition, apathy, and psychosis. With the discovery of this mutation,
      studies have begun to characterize the different phenotypes associated with this
      mutation in terms of epidemiology, clinical presentation, imaging, and pathology.
      Greater awareness and increased surveillance for this mutation will benefit
      patients and their families in terms of access to genetic counseling, research
      studies, and improved understanding of the disease process.

PMID- 26198890
TI  - Effect of very early mobilisation on functional status in patients with acute
      stroke: a single-blind, randomized controlled trail.
AB  - OBJECTIVE: To evaluate the effect of very early mobilisation on functional status
      following acute stroke. DESIGN: Single blind, randomized controlled trial.
      SETTING: University hospital. SUBJECTS: Eighty-six patients with acute stroke (42
      men and 38 women) aged 30-80 years were randomized to an Intervention group and a
      Standard care group. INTERVENTIONS: All participants received 45 minutes standard
      care once a day for seven days. In addition, the intervention group (n=43)
      performed very early mobilisation consisting of early and frequent out of bed
      activities which started within 24 hours of stroke onset for 5 to 30 minutes at
      least twice a day, for seven days. OUTCOME MEASURES: Functional status was
      measured with Barthel ADL Index on admission, discharge and three months follow
      up. RESULTS: Intervention group showed a significant improvement in Barthel Index
      change scores (discharge - admission) (median=35, IQR=30-38.75 versus
      median=17.50, IQR=10-30) than the standard care group. Intervention group showed
      a significant improvement in Barthel Index change scores (three month follow up -
      admission) (median=42.50, IQR=35-55) versus (median=30, IQR=20-35) than the
      standard care group. The Intervention group reported statistically significant
      improvement in functional status at discharge (P<0.001) and at three months
      follow up (P<0.001) compared with the Standard care group. CONCLUSIONS: The
      results indicate that very early mobilisation in addition to the standard care
      may be effective in improving the functional status following acute stroke.

PMID- 26198889
TI  - Postural Tachycardia Syndrome: Beyond Orthostatic Intolerance.
AB  - Postural tachycardia syndrome (POTS) is a form of chronic orthostatic intolerance
      for which the hallmark physiological trait is an excessive increase in heart rate
      with assumption of upright posture. The orthostatic tachycardia occurs in the
      absence of orthostatic hypotension and is associated with a >6-month history of
      symptoms that are relieved by recumbence. The heart rate abnormality and
      orthostatic symptoms should not be caused by medications that impair autonomic
      regulation or by debilitating disorders that can cause tachycardia. POTS is a
      "final common pathway" for a number of overlapping pathophysiologies, including
      an autonomic neuropathy in the lower body, hypovolemia, elevated sympathetic
      tone, mast cell activation, deconditioning, and autoantibodies. Not only may
      patients be affected by more than one of these pathophysiologies but also the
      phenotype of POTS has similarities to a number of other disorders, e.g., chronic
      fatigue syndrome, Ehlers-Danlos syndrome, vasovagal syncope, and inappropriate
      sinus tachycardia. POTS can be treated with a combination of non-pharmacological
      approaches, a structured exercise training program, and often some
      pharmacological support. 

PMID- 26198891
TI  - Systematic review of adjunct therapies to improve outcomes following botulinum
      toxin injection for treatment of limb spasticity.
AB  - OBJECTIVE: To determine the quality of evidence from randomized controlled trials
      on the efficacy of adjunct therapies following botulinum toxin injections for
      limb spasticity. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and Cochrane Central
      Register of Controlled Trials electronic databases were searched for English
      language human studies from 1980 to 21 May 2015. STUDY SELECTION: Randomized
      controlled trials assessing adjunct therapies postbotulinum toxin injection for
      treatment of spasticity were included. Of the 268 studies screened, 17 met
      selection criteria. DATA EXTRACTION: Two reviewers independently assessed risk of
      bias using the Physiotherapy Evidence Database (PEDro) scale and graded according
      to Sackett's levels of evidence. DATA SYNTHESIS: Ten adjunct therapies were
      identified. Evidence suggests that adjunct use of electrical stimulation,
      modified constraint-induced movement therapy, physiotherapy (all Level 1),
      casting and dynamic splinting (both Level 2) result in improved Modified Ashworth
      Scale scores by at least 1 grade. There is Level 1 and 2 evidence that adjunct
      taping, segmental muscle vibration, cyclic functional electrical stimulation, and
      motorized arm ergometer may not improve outcomes compared with botulinum toxin
      injections alone. There is Level 1 evidence that casting is better than taping,
      taping is better than electrical stimulation and stretching, and extracorporeal
      shock wave therapy is better than electrical stimulation for outcomes including
      the Modified Ashworth Scale, range of motion and gait. All results are based on
      single studies. CONCLUSION: There is high level evidence to suggest that adjunct
      therapies may improve outcomes following botulinum toxin injection. No results
      have been confirmed by independent replication. All interventions would benefit
      from further study.

PMID- 26198892
TI  - The effectiveness of behaviour change interventions to increase physical activity
      participation in people with multiple sclerosis: a systematic review and meta
      analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis was conducted to illustrate
      whether people with multiple sclerosis engage in more physical activity following
      behaviour change interventions. DATA RESOURCES: MEDLINE, CINAHL, PubMed, Web of
      Sciences, Cochrane Library, SCOPUS, EMBASE and PEDro were searched from their
      inception till 30 April 2015. TRIAL SELECTION: Randomized and clinical controlled
      trials that used behaviour change interventions to increase physical activity in
      people with multiple sclerosis were selected, regardless of type or duration of
      multiple sclerosis or disability severity. DATA EXTRACTION: Data extraction was
      conducted by two independent reviewers and the Cochrane Collaboration's
      recommended method was used to assess the risk of bias of each included study.
      RESULTS: A total of 19 out of 573 studies were included. Focusing on trials
      without risk of bias, meta-analysis showed that behaviour change interventions
      can significantly increase physical activity participation (z = 2.20, p = 0.03,
      standardised main difference 0.65, 95% confidence interval 0.07 to 1.22, 3
      trials, I(2) = 68%) (eight to 12 weeks' duration). Behaviour change interventions
      did not significantly impact on the physical components of quality of life or
      fatigue. CONCLUSION: Behaviour change interventions provided for relatively short
      duration (eight to 12 weeks) may increase the amount of physical activity people
      with multiple sclerosis engage in, but appear to have no effect on the physical
      components of quality of life and fatigue. Further high quality investigations of
      the efficacy of behaviour change interventions to increase physical activity
      participation that focus on dose, long-term impact and method of delivery are
      warranted for people with multiple sclerosis.

PMID- 26198893
TI  - Influence of illusory kinesthesia by vibratory tendon stimulation on acute pain
      after surgery for distal radius fractures: a quasi-randomized controlled study.
AB  - OBJECTIVES: We investigated the effects of inducing an illusion of motion by
      tendon vibration on sensory and emotional aspects of pain and range of motion in
      patients with fractures of the distal radius. DESIGN: A quasi-randomized
      controlled trial. SETTING: Kawachi General Hospital, Japan. SUBJECTS: A total of
      26 patients with fractures of the distal radius were distributed quasi-randomly
      to either the illusory kinesthesia group (n = 13) or control group (n = 13).
      INTERVENTION: The intervention was performed on seven consecutive days from
      postoperative Day 1. Evaluation was performed at seven days, one month, and two
      months after the surgery. MAIN MEASURES: Data were collected for pain at rest,
      movement pain, the pain catastrophizing scale, the Hospital Anxiety and
      Depression Scale, and range of motion. RESULTS: The illusory kinesthesia group
      reported improved pain at rest (p < 0.001), movement pain (p < 0.001), pain
      catastrophizing scale (p < 0.001), Hospital Anxiety and Depression Scale (p <
      0.01), and range of motion (p < 0.05) compared with the control group at seven
      days, one month, and two months after the surgery. The mean (SD) score of the
      visual analogue scale of pain at rest was 51.3 (16.8) at one day and 4.2 (4.7) at
      seven days in the illusory kinesthesia group, and 56.8 (22.1) at one day and 35.5
      (16.2) at seven days in the control group. CONCLUSION: Illusory kinesthesia group
      improves the sensory and emotion aspects of pain in patients with fractures of
      the distal radius.

PMID- 26198894
TI  - Prevalence of eosinophilia in hospitalized patients with asthma exacerbation.
AB  - BACKGROUND: Recent studies have identified the "eosinophilic phenotype" of asthma
      that is characterized by persistent eosinophilic inflammation and frequent
      exacerbations. However, the prevalence of eosinophilia in patients hospitalized
      for asthma exacerbation is not known. METHODS: We performed a pilot study in two
      sites participating in a multicenter chart review project of children and adults
      hospitalized for asthma exacerbation during 2012-2013. The pilot study
      investigated the prevalence of blood eosinophilia in this patient population.
      Eosinophilia was defined as a count of >=300 cells/microliter at some time during
      the hospitalization. RESULTS: Among 80 patients hospitalized for asthma
      exacerbation, 47 (59%) underwent CBC with differential and had data on blood
      eosinophil count. These 47 comprised the analytic cohort. The median patient age
      was 32 years (IQR, 24-44 years), and 51% were female. Overall, 40% (95% CI, 26%
      56%) of patients had eosinophilia. Although statistical power was limited, there
      were no statistically significant differences in patient characteristics or
      hospital course between patients with eosinophilia and those without (all P >
      0.05). CONCLUSION: Our pilot study showed that 40% of patients hospitalized for
      asthma exacerbation had eosinophilia. The clinical meaning of this biomarker in
      the emergency department/inpatient setting requires further study in much larger
      samples with long-term follow-up; such studies appear feasible.

PMID- 26198895
TI  - A randomized phase II study of the clinical effects of ultrasonically activated
      coagulating shears (Harmonic scalpel) in open gastrectomy for gastric cancer.
AB  - PURPOSE: The Harmonic Ace ultrasonic scalpel has been popular in abdominal
      surgery; however, only a few clinical studies have evaluated the efficacy of this
      device in radical open gastrectomy for gastric cancer. METHODS: The present study
      was designed as a multicenter, prospective, randomized, controlled trial.
      Patients with resectable gastric cancer were randomly assigned to gastrectomy
      using the Harmonic scalpel or conventional monopolar electrosurgery. RESULTS: A
      total of 248 patients were enrolled, and 123 patients were included in the
      Harmonic group and 114 patients were included in the conventional group. The
      demographics of the patients were well balanced between the groups. There was no
      significant difference in the length of the operation from skin incision to
      resection of the gastric specimen (141 +/- 36 min in the Harmonic group vs. 147
      +/- 13 min in the conventional group; p = 0.276) nor in the amount of blood lost
      (365 +/- 293 vs. 336 +/- 272 mL; p = 0.434). There was also no significant
      difference in the incidence of surgical complications or the post-surgical
      hospital stay between the groups. CONCLUSION: The Harmonic scalpel procedure was
      not superior to the conventional monopolar electrosurgery with regard to reducing
      the length of the operation, blood loss, postoperative complications, or
      postoperative hospital stay in radical open gastrectomy.

PMID- 26198896
TI  - Effects of robotic rectal surgery on sexual and urinary functions in male
      patients.
AB  - PURPOSES: This study prospectively assessed the sexual and urinary functions, as
      well as factors influencing these functions, in patients who underwent open or
      robotic surgery for rectal cancer. METHODS: Forty-five consecutive male patients
      who underwent rectal resection for rectal cancer were prospectively enrolled in
      this study. Their sexual and urinary functions were assessed through self
      administered questionnaires comprising the International Index of Erectile
      Function (IIEF; sexual function) and the International Prostate Symptom Score
      (IPSS; urinary function) before and at 3, 6, and 12 months after surgery.
      RESULTS: Fifteen patients who underwent robotic surgery and 22 who underwent open
      surgery were finally analyzed in this study. The total IIEF score and the
      individual score items did not change at 3, 6 or, 12 months after open or robotic
      surgery compared with the preoperative values. However, a univariate analysis
      revealed that age affected the urinary function 12 months after surgery, while
      both univariate and multivariate analyses revealed that postoperative
      complications affected the sexual function 12 months after surgery. CONCLUSIONS:
      In this non-randomized comparison, the postoperative sexual and urinary functions
      were comparable between patients who underwent open rectal surgery and those who
      underwent robotic rectal surgery. Postoperative complications were a risk factor
      for sexual dysfunction, while age was a risk factor for urinary dysfunction.

PMID- 26198898
TI  - Hybrid video-assisted and limited open (VALO) resection of superior sulcus
      tumors.
AB  - PURPOSE: To compare the postoperative recovery of patients with superior sulcus
      tumors (Pancoast tumors) following conventional open surgery vs. a hybrid video
      assisted and limited open approach (VALO). METHODS: The subjects of this
      retrospective study were 20 patients we operated on to resect a Pancoast tumor.
      All patients received induction chemo-radiation followed by surgery, performed
      via either a conventional thoracotomy approach (n = 10) or the hybrid VALO
      approach (n = 10). In the hybrid VALO group, lobectomy and internal chest wall
      preparation were performed using a video technique, with rib resection and
      specimen removal through a limited incision. RESULTS: There was no mortality in
      either group. Two patients from the thoracotomy group required mechanical
      ventilation, but there was no major morbidity in the hybrid VALO group. The
      operative times were similar for the two procedures. The average length of
      hospital stay was shorter and the average pain scores were significantly lower in
      the hybrid VALO group. The incidence of chronic pain was 10 % in the hybrid VALO
      group vs. 50 % in the thoracotomy group. CONCLUSIONS: Hybrid VALO resection of
      Pancoast tumors is feasible and safe, resulting in faster patient recovery and a
      significantly lower incidence of severe chronic pain than open thoracotomy. We
      conclude that centers experienced with video-assisted lobectomy should consider
      hybrid VALO surgery as the procedure of choice for Pancoast tumors.

PMID- 26198897
TI  - Closure versus non-closure of fascial defects in laparoscopic ventral and
      incisional hernia repairs: a review of the literature.
AB  - The laparoscopic technique for repairing ventral and incisional hernias (VIH) is
      now well established. However, several issues related to laparoscopic VIH repair,
      such as the high recurrence rate for hernias with large fascial defects and in
      extremely obese patients, are yet to be resolved. Additional problems include
      seroma formation, mesh bulging/eventration, and non-restoration of the abdominal
      wall rigidity/function with only bridging of the hernial orifice using standard
      laparoscopic intraperitoneal onlay mesh repair (sIPOM). To solve these problems,
      laparoscopic fascial defect closure with IPOM reinforcement (IPOM-Plus) has been
      introduced in the past decade, and a few studies have reported satisfactory
      outcomes. Although detailed techniques for fascial defect closure and handling of
      the mesh have been published, standardized techniques are yet to be established.
      We reviewed the literature on IPOM-Plus in the PubMed database and identified 16
      reports in which the recurrence rate, incidence of seroma formation, and
      incidence of mesh bulging were 0-7.7, 0-11.4, and 0 %, respectively. Several
      comparison studies between sIPOM and IPOM-Plus seem to suggest that IPOM-Plus is
      associated with more favorable surgical outcomes; however, larger-scale studies
      are essential. 

PMID- 26198899
TI  - Multiparametric MRI analysis for the evaluation of MR-guided high intensity
      focused ultrasound tumor treatment.
AB  - For the clinical application of high intensity focused ultrasound (HIFU) for
      thermal ablation of malignant tumors, accurate treatment evaluation is of key
      importance. In this study, we have employed a multiparametric MRI protocol,
      consisting of quantitative T1, T2, ADC, amide proton transfer (APT), T1rho and
      DCE-MRI measurements, to evaluate MR-guided HIFU treatment of subcutaneous tumors
      in rats. K-means clustering using all different combinations of the endogenous
      contrast MRI parameters (feature vectors) was performed to segment the
      multiparametric data into tissue populations with similar MR parameter values.
      The optimal feature vector for identification of the extent of non-viable tumor
      tissue after HIFU treatment was determined by quantitative comparison between
      clustering-derived and histology-derived non-viable tumor fractions. The highest
      one-to-one correspondence between these clustering-based and histology-based non
      viable tumor fractions was observed for the feature vector {ADC, APT-weighted
      signal} (R(2) to line of identity (R(2)y=x) = 0.92) and the strongest agreement
      was seen 3 days after HIFU (R(2)y=x = 0.97). To compare the multiparametric MRI
      analysis results with conventional HIFU monitoring and evaluation methods, the
      histology-derived non-viable tumor fractions were also quantitatively compared
      with non-perfused tumor fractions (derived from the level of contrast enhancement
      in the DCE-MRI measurements) and 240 CEM tumor fractions (i.e. thermal dose > 240
      cumulative equivalent minutes at 43  degrees C). The correlation between
      histology-derived non-viable tumor fractions directly after HIFU and the 240 CEM
      fractions was high, but not significant. The non-perfused fractions overestimated
      the extent of non-viable tumor tissue directly after HIFU, whereas an
      underestimation was observed 3 days after HIFU. In conclusion, we have shown that
      a multiparametric MR analysis, especially based on the ADC and the APT-weighted
      signal, can potentially be used to determine the extent of non-viable tumor
      tissue 3 days after HIFU treatment. We expect that this method can be
      incorporated in the current clinical workflow of MR-HIFU ablation therapies.

PMID- 26198907
TI  - ERRATUM: The Growing Number of Hemophilia Registries: Quantity vs. Quality.

PMID- 26198903
TI  - Metabolite profiling of CHO cells: Molecular reflections of bioprocessing
      effectiveness.
AB  - Whilst development of medium and feeds has provided major advances in recombinant
      protein production in CHO cells, the fundamental understanding is limited. We
      have applied metabolite profiling with established robust (GC-MS) analytics to
      define the molecular loci by which two yield-enhancing feeds improve recombinant
      antibody yields from a model GS-CHO cell line. With data across core metabolic
      pathways, that report on metabolism within several cellular compartments, these
      data identify key metabolites and events associated with increased cell survival
      and specific productivity of cells. Of particular importance, increased process
      efficiency was linked to the functional activity of the mitochondria, with the
      amount and time course of use/production of intermediates of the citric acid
      cycle, for uses such as lipid biosynthesis, precursor generation and energy
      production, providing direct indicators of cellular status with respect to
      productivity. The data provide clear association between specific cellular
      metabolic indicators and cell process efficiency, extending from prior
      indications of the relevance of lactate metabolic balance to other redox sinks
      (glycerol, sorbitol and threitol). The information, and its interpretation,
      identifies targets for engineering cell culture efficiency, either from genetic
      or environmental perspectives, and greater understanding of the significance of
      specific medium components towards overall CHO cell bioprocessing. 

PMID- 26198908
TI  - Sugar or spice: Using I3 metatheory to understand how and why glucose reduces
      rejection-related aggression.
AB  - Social rejection can increase aggression, especially among people high in
      rejection sensitivity. Rejection impairs self-control, and deficits in self
      control often result in aggression. A dose of glucose can counteract the effect
      of situational factors that undermine self-control. But no research has
      integrated these literatures to understand why rejection increases aggression,
      and how to reduce it. Using the I(3) model of aggression, we proposed that
      aggression would be highest under conditions of high instigation (rejection),
      high impellance (high rejection sensitivity), and low inhibition (drinking a
      beverage sweetened with a sugar substitute instead of glucose). As predicted,
      aggression was highest among participants who experienced social rejection, were
      high in rejection sensitivity, and drank a placebo beverage. A dose of glucose
      reduced aggression, especially among rejected people high in rejection
      sensitivity. These findings point to the importance of self-control in
      understanding why social rejection increases aggression, and how to prevent it.

PMID- 26198909
TI  - The dental pulp stem cell niche based on aldehyde dehydrogenase 1 expression.
AB  - AIM: To detect cells expressing the stem cell marker ALDH1 (aldehyde
      dehydrogenase1) in the pulp of human permanent teeth and to investigate the
      expression of ALDH1 in isolated dental pulp cells. METHODOLOGY: Pulp tissue was
      collected and processed for immunohistochemistry to detect ALDH1-, STRO-1- and
      CD90-positive cells. In addition, cells were isolated and analysed by flow
      cytometry for ALDH1 activity and for the cell surface markers CD44, CD73, CD90,
      STRO-1 and CD45. Cells were also examined for multidifferentiation capacity.
      Within these cells, an ALDH1(+) cell subpopulation was selected and evaluated for
      multidifferentiation capacity. RESULTS: The immunohistochemistry analyses showed
      that ALDH1-, CD90- and STRO-1-positive cells were located mainly in the
      perivascular areas and nerve fibres of dental pulps. Cells on the fifth passage
      had high expression for CD44, CD73 and CD90, whereas moderate labelling was
      observed for STRO-1 and ALDH1 in flow cytometry analysis. On the same passages,
      cells were able to differentiate into osteogenic, adipogenic and chondrogenic
      lineages. The ALDH1(+) cell subpopulation also demonstrated multilineage
      differentiation ability. CONCLUSIONS: Dental pulp stem cells reside in the
      vicinity of blood vessels and nerve fibres, indicating the possible existence of
      more than one stem cell niche in dental pulps. Furthermore, ALDH1 was expressed
      by isolated dental pulp cells, which had mesenchymal stem cell characteristics.
      Thus, it can be suggested that ALDH1 may be used as a DPSC marker.

PMID- 26198910
TI  - Study of detecting mechanism of carbon nanotubes gas sensor based on multi-stable
      stochastic resonance model.
AB  - The detecting mechanism of carbon nanotubes gas sensor based on multi-stable
      stochastic resonance (MSR) model was studied in this paper. A numerically
      stimulating model based on MSR was established. And gas-ionizing experiment by
      adding electronic white noise to induce 1.65 MHz periodic component in the carbon
      nanotubes gas sensor was performed. It was found that the signal-to-noise ratio
      (SNR) spectrum displayed 2 maximal values, which accorded to the change of the
      broken-line potential function. The experimental results of gas-ionizing
      experiment demonstrated that periodic component of 1.65 MHz had multiple MSR
      phenomena, which was in accordance with the numerical stimulation results. In
      this way, the numerical stimulation method provides an innovative method for the
      detecting mechanism research of carbon nanotubes gas sensor. 

PMID- 26198911
TI  - Cerebrospinal fluid angiotensin-converting enzyme for diagnosis of
      neurosarcoidosis.
AB  - BACKGROUND: Neurosarcoidosis (NS) is a rare condition that may mimic central
      nervous system (CNS) infection, neoplasia and other inflammatory disorders of the
      CNS such as multiple sclerosis, encephalitis and vasculitis. Diagnosis is
      challenging in cases with minimal or absent systemic involvement. Cerebrospinal
      fluid (CSF) angiotensin-converting enzyme (c-ACE) has been claimed as a valuable
      diagnostic tool for NS. However, there is little data evaluating its performance
      in routine clinical practice. FINDINGS: We performed a monocentric,
      retrospective, chart-based study including all patients investigated with a
      lumbar puncture and c-ACE dosage for suspected NS between 01/01/2006 and
      31/12/2012 at the Geneva University Hospital. Receiver-operating characteristic
      (ROC) curve and area under the curve (AUC) were performed to calculate the
      optimal cut-off value of c-ACE and to determine the discriminative ability of c
      ACE. Of the 440 patients included in the study, 9 were diagnosed with NS on the
      basis of tissue biopsy. Mean c-ACE was not significantly different between NS and
      non-NS patients. With a cut-off value of 2 (0-2 vs >=3), sensitivity and
      specificity of c-ACE were 66.7% and 67.3%, respectively. CONCLUSIONS: In our
      clinical setting, the sensitivity and specificity of c-ACE for NS diagnosis were
      relatively poor and of little clinical utility.

PMID- 26198912
TI  - Reduction of inflammation and preservation of neurological function by anti-CD52
      therapy in murine experimental autoimmune encephalomyelitis.
AB  - Alemtuzumab, a monoclonal antibody directed against human CD52, is used in the
      treatment of MS. To characterize the impact of anti-CD52 administration, a
      monoclonal antibody to mouse CD52 (anti-muCD52) was generated and evaluated in
      EAE mouse models of MS. A single course of anti-muCD52 provided a therapeutic
      benefit accompanied by a reduction in the frequency of autoreactive T lymphocytes
      and production of pro-inflammatory cytokines. Examination of the CNS revealed a
      decrease in infiltrating lymphocytes, demyelination and axonal loss.
      Electrophysiological assessment showed preservation of axonal conductance in the
      spinal cord. These findings suggest that anti-CD52 therapy may help preserve CNS
      integrity. 

PMID- 26198913
TI  - Safety and efficacy of reduced fingolimod dosage treatment.
AB  - BACKGROUND: Oral fingolimod is a sphingosine-1-phosphate-receptor modulator that
      prevents the egress of lymphocytes from lymph nodes. Fingolimod reduces relapse
      rate and delays disability progression in patients with relapsing forms of
      multiple sclerosis (MS). Elevation of liver function tests (LFTs) and reduction
      in peripheral-blood lymphocyte counts were among the most common adverse events
      reported in phase II, phase III, and extension studies. OBJECTIVE: To describe
      eight patients in whom fingolimod dose was reduced to every other day (n=6) or
      every third day (n=2) due to increased LFTs more than 3 times the upper limit of
      normal (ULN) (n=2) or decreased lymphocyte count by <=0.2*10(9)/L (n=6). RESULTS:
      Fingolimod dose reduction resulted in reversal of laboratory abnormalities.
      Clinically, none of the 8 patients developed clinical relapses, but five patients
      had new lesions on magnetic resonance imaging (MRI), one of whom with disability
      progression, and one patient converted to secondary progressive MS (SPMS).
      CONCLUSION: Reducing the frequency of fingolimod administration can reverse
      laboratory abnormalities but may have a negative impact on drug efficacy.

PMID- 26198914
TI  - Low dose fumaric acid esters are effective in a mouse model of spontaneous
      chronic encephalomyelitis.
AB  - In this study we examined the role of fumaric acid esters (FAE) in a spontaneous
      and chronic animal model, the opticospinal EAE (OSE). Preventive treatment of
      dimethylfumarate (DMF) promotes onset of disease in animals treated with high
      dose DMF. This group also exhibited a significantly exacerbated disease course in
      a therapeutic treatment as compared to the low dose DMF approach, where less
      demyelination, macrophage infiltration, and increased Nrf2 expression in the
      spinal cord were observed. We conclude that low dose DMF treatment is effective
      in the therapy of the spontaneous opticospinal EAE model and mediates
      neuroprotective effects via the oxidative stress response pathway. 

PMID- 26198915
TI  - Intermittent fasting modulates IgA levels in the small intestine under intense
      stress: a mouse model.
AB  - Intermittent fasting prolongs the lifespan and unlike intense stress provides
      health benefits. Given the role of the immunoglobulin A (IgA) in the intestinal
      homeostasis, the aim of this study was to assess the impact of intermittent
      fasting plus intense stress on secretory IgA (SIgA) production and other mucosal
      parameters in the duodenum and ileum. Two groups of six mice, with intermittent
      fasting or fed ad libitum for 12weeks, were submitted to a session of intense
      stress by a bout of forced swimming. Unstressed ad libitum fed or intermittently
      fasted groups were included as controls. After sacrifice, we evaluated intestinal
      SIgA and plasma adrenal hormones, lamina propria IgA+ plasma-cells, mRNA
      expression of polymeric immunoglobulin receptor, alpha- and J-chains in the liver
      and intestinal mucosa, as well as pro- (tumor necrosis factor-alpha, interleukin
      6 and Interferon-gamma) and anti- (interleukin-2, -4, -10 and transforming growth
      factor-beta) inflammatory cytokines in mucosal samples. Under intense stress,
      intermittent fasting down- or up-modulated the levels of most parameters in the
      duodenum and ileum, respectively while up-regulated corticosterone levels without
      affecting epinephrine. Our data suggest intermittent fasting plus intense stress
      elicited neuroendocrine pathways that differentially controlled IgA and pIgR
      expression in duodenum and ileum. These findings provide experimental foundations
      for a presumable impact of intermittent fasting under intense stress on the
      intestinal homeostasis or inflammation by triggering or reducing the IgA
      production in ileum or duodenum respectively. 

PMID- 26198916
TI  - Robust increase of microglia proliferation in the fornix of hippocampal axonal
      pathway after a single LPS stimulation.
AB  - Microglia are resident immunocompetent cells having important roles in innate
      immunity in the brains. In the present study, we found that a single
      lipopolysaccharide (LPS) administration significantly increased microglial
      proliferation in the fornix and dentate gyrus (DG) but not the cerebral cortex
      and corpus callosum of adult mice. LPS-induced microglial proliferation was
      especially robust at the white matter of the fornix. The density of microglia
      increased in the fornix and DG for roughly one week and returned to basal levels
      at least 20days after a single LPS administration. Consecutive LPS administration
      did not induce such dramatic increase of microglial proliferation in the fornix.
      The inhibition of vascular endothelial growth factor signaling by AZD2171 largely
      suppressed LPS-induced increase of microglial proliferation in the fornix. In
      conclusion, the present study indicates that the hippocampal neuronal system has
      a higher proliferative microglial capability against LPS-induced inflammatory
      administration compared with other brain regions. 

PMID- 26198917
TI  - Compartmentalized intrathecal immunoglobulin synthesis during HIV infection - a
      model of chronic CNS inflammation?
AB  - HIV infects the central nervous system (CNS) during primary infection and
      persists in resident macrophages. CNS infection initiates a strong local immune
      response that fails to control the virus but is responsible for by-stander
      lesions involved in neurocognitive disorders. Although highly active anti
      retroviral therapy now offers an almost complete control of CNS viral
      proliferation, low-grade CNS inflammation persists. This review focuses on HIV
      induced intrathecal immunoglobulin (Ig) synthesis. Intrathecal Ig synthesis early
      occurs in more than three-quarters of patients in response to viral infection of
      the CNS and persists throughout the course of the disease. Viral antigens are
      targeted but this specific response accounts for <5% of the whole intrathecal
      synthesis. Although the nature and mechanisms leading to non-specific synthesis
      are unknown, this prominent proportion is comparable to that observed in various
      CNS viral infections. Cerebrospinal fluid-floating antibody-secreting cells
      account for a minority of the whole synthesis, which mainly takes place in
      perivascular inflammatory infiltrates of the CNS parenchyma. B-cell traffic and
      lineage across the blood-brain-barrier have not yet been described. We review
      common technical pitfalls and update the pending questions in the field.
      Moreover, since HIV infection is associated with an intrathecal chronic
      oligoclonal (and mostly non-specific) Ig synthesis and associates with low-grade
      axonal lesions, this could be an interesting model of the chronic intrathecal
      synthesis occurring during multiple sclerosis. 

PMID- 26198918
TI  - The frequencies of Killer immunoglobulin-like receptors and their HLA ligands in
      chronic inflammatory demyelinating polyradiculoneuropathy are similar to those in
      Guillian Barre syndrome but differ from those of controls, suggesting a role for
      NK cells in pathogenesis.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired
      inflammatory neuropathy, which has similar clinical and pathological features to
      Guillain-Barre Syndrome (GBS), but differs in time course. We investigated the
      frequency of genes encoding Killer immunoglobulin-like receptors and their HLA
      ligands in subjects with CIDP, in subjects with GBS and in healthy controls.
      There were no differences in KIR gene frequency among the 3 groups. The gene
      frequencies for HLA-B Bw4-I were significantly greater in CIDP than HC, but did
      not differ from GBS. The frequency of the combination of 3DL1/HLA-B Bw4I was
      greater in CIDP than HC, but did not differ from that of GBS. These data raise
      the possibility of NK cell function being an important factor in the pathogenesis
      of CIDP. 

PMID- 26198919
TI  - Gender influence in EBV antibody response in multiple sclerosis patients from
      Kuwait.
AB  - BACKGROUND: Epstein-Barr virus (EBV) infection is implicated with multiple
      sclerosis (MS) risk, exacerbation, and progression. The HLA-DRB1*1501 haplotype
      is a strong MS risk factor consistently documented in MS populations. There are
      no studies of EBV infections and HLA-DRB1*1501 haplotype associating with MS from
      Kuwait where MS prevalence has increased significantly. OBJECTIVES: To determine
      the association of EBV infection with MS incidence, and to investigate HLA
      DRB1*1501 as a potential genetic risk factor for MS in Kuwait. METHODS: This is a
      case-control study involving 141 MS patients and 40 healthy controls. Antibody
      titers against EBV antigens' viral capsid antigen (VCA) and Epstein-Barr nuclear
      antigen 1 (EBNA1) were measured using enzyme-linked immunosorbent assays. HLA
      DRB1*1501 haplotype assessment was done using rs3135005 TaqMan genotyping assay.
      RESULTS: Antibody titers against EBV were significantly elevated in MS patients
      compared to healthy controls (anti-EBNA1, p=0.008; anti-VCA, p=0.028). MS males
      had higher antibody titers to EBNA1 than healthy male controls (p=0.005) and
      female MS patients (p=0.03). HLA-DRB1*1501 haplotype genotypes failed to generate
      a risk association with MS or EBV antibody titers (p=0.6). CONCLUSION: An
      increased immune response to EBV infection is associated with MS incidence
      influenced by the type of antigen and sex. HLA-DRB1*1501 haplotype is not
      associated with MS risk in our Kuwaiti MS cohort.

PMID- 26198920
TI  - Family-based association study of interleukin 6 (IL6) and its receptor (IL6R)
      functional polymorphisms in schizophrenia in the Polish population.
AB  - Schizophrenia is a heterogeneous disorder and its etiology remains incompletely
      elucidated. Among possible causes, immunological factors have been implicated in
      its pathogenesis and course. The inflammatory system may trigger or modulate the
      course of schizophrenia through complex mechanisms influencing neurodevelopment,
      neuroplasticity and neurotransmission. Recent studies indicate a role of
      excessive interleukin-6 (IL6) signaling in the pathogenesis of schizophrenia.
      Findings regarding changes in the circulating levels of soluble interleukin-6
      receptor (sIL6R) in schizophrenia have been equivocal. The study was performed on
      a group of 147 trio (patients diagnosed with schizophrenia and their healthy
      parents). Polymorphisms of IL6 (rs1800795, rs1800797) and IL6R (rs4537545,
      rs4845617, rs2228145) genes were genotyped with the use of TaqMan SNP Genotyping
      Assays. No association of the polymorphisms from IL6 and IL6R genes with
      schizophrenia was found. We also investigated haplotypes in IL6 gene (consisting
      of rs1800795 and rs1800797) and in IL6R gene (consisting of rs4537545,
      rs2228145). We also found no preference in transmission of any haplotype. Our
      results do not support the theory that polymorphisms of IL6 and IL6R genes are
      involved in the pathogenesis of schizophrenia. It seems advisable to carry out
      further examinations of the role of these polymorphisms in schizophrenia by means
      of TDT method and classical (case-control) association method. 

PMID- 26198921
TI  - A phase IIa randomized clinical study testing GNbAC1, a humanized monoclonal
      antibody against the envelope protein of multiple sclerosis associated endogenous
      retrovirus in multiple sclerosis patients - a twelve month follow-up.
AB  - GNbAC1 is a humanized monoclonal antibody targeting MSRV-Env, an endogenous
      retroviral protein, which is expressed in multiple sclerosis (MS) lesions, is pro
      inflammatory and inhibits oligodendrocyte precursor cell differentiation. This
      paper describes the open-label extension up to 12months of a trial testing GNbAC1
      in 10 MS patients at 2 and 6mg/kg. The primary objective was to assess GNbAC1
      safety, and other objectives were pharmacokinetic and pharmacodynamic
      assessments. During the extended study, no safety issues occurred in the 8
      remaining patients. No anti-GNbAC1 antibodies were detected. GNbAC1 appears well
      tolerated. 

PMID- 26198922
TI  - Immature dendritic cell exosomes suppress experimental autoimmune myasthenia
      gravis.
AB  - Immature dendritic cell-derived exosomes (iMDEX) display a certain degree of
      immunosuppressive activity in autoimmune diseases. However, the role of iMDEX in
      experimental autoimmune myasthenia gravis (EAMG) is still unclear. Therefore, we
      tested the effects of mouse bone marrow (BM)-derived iMDEX on tolerance induction
      in a mouse model of EAMG. In this study, we found that the CELLine culture system
      produced more exosomes, the morphology and phenotype of these exosomes were found
      to be identical when compared with traditional cell culture. And, iMDEX(1000)
      ameliorated the progression of EAMG by reducing AChR-reactive lymphocyte
      proliferation, AChR antibody levels and pro-inflammatory cytokine levels. 

PMID- 26198923
TI  - Differential regulation of macrophage phenotype by mature and pro-nerve growth
      factor.
AB  - To characterize the role of neurotrophin receptors on macrophages, we
      investigated the ability of nerve growth factor (NGF) and its precursor, proNGF,
      to regulate human macrophage phenotype. The p75 neurotrophin receptor (p75(NTR))
      and TrkA were concentrated within overlapping domains on membrane ruffles. NGF
      stimulation of macrophages increased membrane ruffling, calcium spiking,
      phagocytosis and growth factor secretion. In contrast, proNGF induced podosome
      formation, increased migration, suppressed calcium spikes and increased
      neurotoxin secretion. These results demonstrate opposing roles of NGF and proNGF
      in macrophage regulation providing new avenues for pharmacological intervention
      during neuroinflammation. 

PMID- 26198924
TI  - The OVLT initiates the fall in arterial pressure evoked by high dose
      lipopolysaccharide: evidence that dichotomous, dose-related mechanisms mediate
      endotoxic hypotension.
AB  - This study tested the hypothesis that lipopolysaccharide (LPS) lowers arterial
      pressure through two different mechanisms depending on the dose. Previously, we
      found that a low hypotensive dose of LPS (1mg/kg) lowers arterial pressure by
      activating vagus nerve afferents. Here we report that hypotension evoked by high
      dose LPS (15mg/kg) can be prevented by injecting lidocaine into the OVLT but not
      by vagotomy or inactivation of the NTS. The hypotension produced by both LPS
      doses was correlated with elevated extracellular norepinephrine concentrations in
      the POA and prevented by blocking alpha-adrenergic receptors. Thus, initiation of
      endotoxic hypotension is dose-related, mechanistically. 

PMID- 26198926
TI  - HIV-1 differentially modulates autophagy in neurons and astrocytes.
AB  - Autophagy, a lysosomal degradative pathway that maintains cellular homeostasis,
      has emerged as an innate immune defense against pathogens. The role of autophagy
      in the deregulated HIV-infected central nervous system (CNS) is unclear. We have
      found that HIV-1-induced neuro-glial (neurons and astrocytes) damage involves
      modulation of the autophagy pathway. Neuro-glial stress induced by HIV-1 led to
      biochemical and morphological dysfunctions. X4 HIV-1 produced neuro-glial
      toxicity coupled with suppression of autophagy, while R5 HIV-1-induced toxicity
      was restricted to neurons. Rapamycin, a specific mTOR inhibitor (autophagy
      inducer) relieved the blockage of the autophagy pathway caused by HIV-1 and
      resulted in neuro-glial protection. Further understanding of the regulation of
      autophagy by cytokines and chemokines or other signaling events may lead to
      recognition of therapeutic targets for neurodegenerative diseases. 

PMID- 26198925
TI  - Promiscuity of autoimmune responses to MBP after stroke.
AB  - In this study we examined Th1 and Th17 immune responses to rat myelin basic
      protein (MBP), bovine MBP, human MBP, MBP 68-86, MBP 63-81 and ovalbumin in Lewis
      rats to determine which MBP antigen is recognized following ischemic brain
      injury. Responses were compared to animals immunized to rat MBP. Data show that
      immune responses following immunization with rat MBP are promiscuous with cross
      reaction to MBP from other species. After stroke, few animals develop Th1 or Th17
      responses to MBP, but when those responses occur, especially Th1 responses to rat
      MBP in the brain, they are predictive of worse stroke outcome. 

PMID- 26198927
TI  - Toxoplasma gondii seropositivity is negatively associated with multiple
      sclerosis.
AB  - BACKGROUND: Toxoplasma (T.) gondii is a ubiquitous intracellular parasitic
      protozoan that was recently associated with various autoimmune diseases.
      OBJECTIVES: We aimed to investigate the prevalence of T. gondii IgG and IgM
      antibodies between MS patients and healthy controls. METHODS: Sera from 163 MS,
      91 clinically isolated syndrome cases and 178 age and gender matched controls
      were evaluated for the prevalence of T. gondii IgG antibodies utilizing
      chemiluminescent immunoassay (ARCHITECT). RESULTS: MS-patients showed a
      significantly lower prevalence for T. gondii IgG antibodies compared to controls
      (33.3% vs. 47.9%; p=0.011, OR=1.8 (95% CI 1.2-3.2)). CONCLUSION: The results
      demonstrate a negative association between an infection with the parasite T.
      gondii and the presence of MS.

PMID- 26198928
TI  - Effect of high dose vitamin D intake on interleukin-17 levels in multiple
      sclerosis: a randomized, double-blind, placebo-controlled clinical trial.
AB  - BACKGROUND: Vitamin D has immunomodulatory effects in multiple sclerosis (MS).
      Vitamin D acts through various mechanisms such as secretion of cytokines.
      Interleukin-17 (IL-17) is a critical interleukin in inflammatory response in MS.
      OBJECTIVE: This study assessed the effect of oral high dose vitamin D intake on
      IL-17 levels in MS patients in a double blind randomized clinical trial. METHODS:
      94 patients with a diagnosis of relapsing remitting multiple sclerosis (RRMS)
      were randomized to two groups. One group received 50,000 IU vitamin D3 every five
      days for 12weeks. The other group was given placebo. Both groups received
      interferon-beta (IFN-beta) treatment. Serum levels of IL-17 were measured at the
      beginning of the study and after 12weeks. RESULTS: IL-17 serum levels were
      56.75+/-28.72pg/ml and 30.31+/-75.85pg/ml in the intervention and placebo group
      at the beginning of the study, respectively (Median+/-IQR, p=0.338). After
      12weeks, IL-17 levels were 58.93+/-67.93pg/ml and 46.13+/-94.70pg/ml in the
      intervention and placebo group, respectively (Median+/-IQR, p=0.960). The
      multiple linear regression analysis indicated that the consumption of vitamin D3
      was positively and significantly associated with the logarithm of IL-17 measures
      (beta=1.719; p=0.002 and R2=0.91), adjusted by EDSS scores. CONCLUSION: IL-17
      levels showed significant change in RRMS patients after receiving high dose
      vitamin D3 for 12weeks.

PMID- 26198929
TI  - IL-10 producing B cells partially restore E2-mediated protection against EAE in
      PD-L1 deficient mice.
AB  - Women with multiple sclerosis (MS) often experience clinical improvement during
      pregnancy, indicating that sex hormones might have therapeutic effects in MS. Our
      previous studies have demonstrated that B cells and PD-L1 are crucial for E2
      (17beta-estradiol)-mediated protection against experimental autoimmune
      encephalomyelitis (EAE). We here demonstrate that the transfer of IL-10(+) B
      cells into E2-treated PD-L1(-/-) mice after EAE induction could partially restore
      E2-mediated protection and decrease the frequency of pro-inflammatory cells in
      the CNS compared to E2/saline treated PD-L1(-/-) mice. Hence, co-administration
      of IL-10(+) B cells and E2 might have a powerful therapeutic potential for
      treatment of EAE. 

PMID- 26198930
TI  - Peripheral challenge with a viral mimic upregulates expression of the complement
      genes in the hippocampus.
AB  - Peripheral challenge with a viral mimetic, polyinosinic-polycytidylic acid (PIC)
      induces hippocampal hyperexcitability in mice. Here, we characterized this
      hippocampal response through a whole genome transcriptome analysis.
      Intraperitoneal injection of PIC resulted in temporal dysregulation of 625 genes
      in the hippocampus, indicating an extensive genetic reprogramming. The
      bioinformatics analysis of these genes revealed the complement pathway to be the
      most significantly activated. The gene encoding complement factor B (CfB)
      exhibited the highest response, and its upregulation was commensurate with the
      development of hyperexcitability. Collectively, these results suggest that the
      induction of hippocampal hyperexcitability may be mediated by the alternative
      complement cascades. 

PMID- 26198931
TI  - The effect of proinflammatory cytokines in Cognitive Behavioral Therapy.
AB  - Major depressive disorder (MDD) is a debilitating disorder and its
      pathophysiology is associated with deregulation of the immune system. We
      investigated the changes in circulating levels of proinflammatory cytokines
      (specifically IL-6 and TNF-alpha) measured by the ELISA kit in two
      psychotherapeutic interventions for MDD: Narrative Cognitive Therapy (NCT) and
      Cognitive Behavioral Therapy (CBT). This is a randomized clinical trial including
      97 individuals (18 to 29years-old) with MDD. In CBT there was a significant
      difference in serum levels of IL-6 and TNF-alpha, therefore indicating that CBT
      was more effective than NCT on serum levels proinflammatory cytokines. 

PMID- 26198932
TI  - Central and systemic inflammatory responses to thoracotomy - potential
      implications for acute and chronic postsurgical pain.
AB  - Chronic postsurgical pain (CPSP) may affect up to 70% of patients after surgery.
      Glial and immune mediators have been implicated in the pathogenesis of chronic
      postsurgical pain. Our objective was to study cerebrospinal fluid (CSF) and serum
      concentrations of IL-1beta, IL-6, IL-8, IL-10, IFNgamma and TNFalpha over a 72
      hour period in patients undergoing a thoracotomy and oesophagectomy. Despite
      adequate pain control, thoracotomy was still associated with significant central
      and peripheral inflammation. This must be taken into consideration in planning
      future strategies to prevent CPSP. 

PMID- 26198933
TI  - A diagnostic approach for identifying anti-neuronal antibodies in children with
      suspected autoimmune encephalitis.
AB  - We assessed the validity of immunoblotting, immunohistochemistry (IHC), and
      immunocytochemistry (ICC) to detect anti-neuronal antibodies in an attempt to
      establish a diagnostic approach for pediatric autoimmune encephalitis. Both IHC
      and ICC had higher sensitivity than immunoblotting and could differentiate
      between antibodies directed towards intracellular and cell surface antigens.
      There was a significant correlation between the IHC and ICC results. When
      patients were divided into encephalitis and non-encephalitis groups, there was no
      difference in the positivity rate and staining pattern of IHC and ICC between
      them. In conclusion, IHC and ICC are useful methods to screen for anti-neuronal
      antibodies. A combination of IHC, ICC, and specific cell-based assays is expected
      to be an efficient approach for the diagnosis of autoantibody-mediated
      encephalitis. 

PMID- 26198934
TI  - Association of serum Epstein-Barr nuclear antigen-1 antibodies and intrathecal
      immunoglobulin synthesis in early multiple sclerosis.
AB  - Multiple sclerosis (MS) is associated with Epstein-Barr virus (EBV) infection. A
      characteristic feature of MS is an intrathecal synthesis of immunoglobulin (Ig)G.
      In 90 patients with clinically isolated syndromes/early relapsing-remitting MS,
      serum antibodies to Epstein-Barr nuclear antigen-1, but not to EBV viral capsid
      antigen, rubella, or varicella zoster virus, were higher (p=0.03) in those with
      than those without a calculated intrathecal IgG synthesis >0% and correlated with
      the percentage (r=0.27, p=0.009) and concentration (r=0.27, p=0.012) of
      intrathecally produced IgG. These findings suggest a link between EBV infection
      and the events leading to intrathecal IgG synthesis in patients with MS. 

PMID- 26198935
TI  - Role of Toll-like receptors and retinoic acid inducible gene I in endogenous
      production of type I interferon in dermatomyositis.
AB  - To explore the possible mechanisms implicated in the endogenous production of
      type I interferons within the muscle tissue of dermatomyositis (DM) patients. We
      detected the co-localization of plasmacytoid dendritic cells (pDCs) with Toll
      like receptors (TLRs) and retinoic acid inducible gene (RIG)-I by
      immunohistochemistry and immunofluorescence. Western blotting confirmed the
      expression of TLRs and RIG-I. TLR-3 and RIG-I was preferentially expressed in the
      perifascicular atrophy fibers of DM. TLR-7 was only in inflammatory infiltrates
      of a few DM patients. TLR-4 and TLR-9 was expressed mainly in inflammatory
      infiltrates. Immunofluorescence showed extensive co-localization of BDCA-2 with
      TLR-9 and little co-localization with TLR-7. Western blotting showed upregulation
      of expression of TLRs and RIG-I in DM compared with the controls. Our findings
      indicate that endogenous production of type I IFN in DM is generated by pDCs,
      mainly through the TLR-9 pathway and in part by TLR-7. TLR-3 and RIG-I are
      implicated in the formation of perifascicular atrophy in DM. 

PMID- 26198938
TI  - [Methods, challenges and opportunities for big data analyses of microbiome].
AB  - Microbiome is a novel research field related with a variety of chronic
      inflamatory diseases. Technically, there are two major approaches to analysis of
      microbiome: metataxonome by sequencing the 16S rRNA variable tags, and metagenome
      by shot-gun sequencing of the total microbial (mainly bacterial) genome mixture.
      The 16S rRNA sequencing analyses pipeline includes sequence quality control,
      diversity analyses, taxonomy and statistics; metagenome analyses further includes
      gene annotation and functional analyses. With the development of the sequencing
      techniques, the cost of sequencing will decrease, and big data analyses will
      become the central task. Data standardization, accumulation, modeling and disease
      prediction are crucial for future exploit of these data. Meanwhile, the
      information property in these data, and the functional verification with culture
      dependent and culture-independent experiments remain the focus in future
      research. Studies of human microbiome will bring a better understanding of the
      relations between the human body and the microbiome, especially in the context of
      disease diagnosis and therapy, which promise rich research opportunities. 

PMID- 26198937
TI  - Fingolimod does not enhance cerebellar remyelination in the cuprizone model.
AB  - Fingolimod (FTY720) is approved for treatment of relapsing-remitting multiple
      sclerosis. In vitro studies have found that fingolimod stimulates remyelination
      in cerebellar slices, but in vivo animal studies have not detected any positive
      effect on cerebral remyelination. The discrepant findings could be a result of
      different mechanisms underlying cerebral and cerebellar remyelination. The
      cuprizone model for de- and remyelination was used to evaluate whether fingolimod
      had an impact on cerebellar remyelination in vivo. We found that fingolimod did
      not have any effect on cerebellar remyelination, number of mature
      oligodendrocytes, microglia or astrocytes when fed after cuprizone exposure. 

PMID- 26198936
TI  - Chronic ethanol exposure combined with high fat diet up-regulates P2X7 receptors
      that parallels neuroinflammation and neuronal loss in C57BL/6J mice.
AB  - The present investigation tested the role of ATP-activated P2X7 receptors
      (P2X7Rs) in alcohol-induced brain damage using a model that combines intragastric
      (iG) ethanol feeding and high fat diet in C57BL/6J mice (Hybrid). The Hybrid
      paradigm caused increased levels of pro-inflammatory markers, changes in
      microglia and astrocytes, reduced levels of neuronal marker NeuN and increased
      P2X7R expression in ethanol-sensitive brain regions. Observed changes in P2X7R
      and NeuN expression were more pronounced in Hybrid paradigm with inclusion of
      additional weekly binges. In addition, high fat diet during Hybrid exposure
      aggravated the increase in P2X7R expression and activation of glial cells. 

PMID- 26198939
TI  - [MicroRNA-34a regulates cell cycle by targeting CD44 in human bladder carcinoma
      cells].
AB  - OBJECTIVE: To investigate the role of microRNA-34a (miR-34a) in regulating the
      cell cycles of bladder cancer cell line J82 and explore the underlying mechanism.
      METHODS: J82 cells were transfected with a miR-34a mimic or an inhibitor to
      induce miR-34a overexpression or silencing. The RNA level of miR-34a in the
      transfected cells was detected by real-time PCR, and CD44 expressions at the mRNA
      and protein levels were detected by real-time PCR and Western blotting.
      Luciferase reporter assay was used to detect the activation of 3'UTR of CD44, and
      flow cytometry was performed to analyze the cell cycle changes. RESULTS: The
      expression level of miR-34a was significantly increased and CD44 expression
      significantly lowered in cells transfected with miR-34a mimic; miR-34a inhibitor
      transfection caused reverse effects on miR-34a and CD44 expressions. MiR-34a
      mimics downregulated while miR-34a inhibitor enhanced the activation of 3'UTR of
      CD44 with corresponding changes in the expressions of some cell cycle-related
      proteins. MiR-34a mimics and miR-34a inhibitor induced opposite changes in J82
      cell cycle, which were partly reversed by CD44. CONCLUSION: MiRNA-34a regulates
      cell cycles by targeting CD44 in human bladder carcinoma cell line J82.

PMID- 26198940
TI  - [Role of phospholipid transfer protein in cigarette smoke-induced apoptosis of
      RLE-6TN cells].
AB  - OBJECTIVE: To investigate the role of phospholipid transfer protein (PLTP) in
      cigarette smoke extract (CSE)-induced apoptosis of rat alveolar type II cells
      (RLE-6TN) in vitro. METHODS: Rat alveolar epithelial cell line RLE-6TN were
      transfected with a small interfering RNA (siRNA) targeting PLTP prior to exposure
      to different concentrations of CSE for 24 or 48 h. The morphological changes of
      the apoptotic cells were observed by fluorescence microscopy with Hochest
      staining, and the cell apoptosis rate was measured with flow cytometry. The
      expression level of PLTP and caspase-3 activity in the cells were examined with
      Western blotting. RESULTS: Exposure to CSE significantly increased the cell
      apoptosis rate from (1.68?0.098)% to (18.663?0.964)% (P<0.001). Hoechst staining
      revealed distinct apoptotic changes in CSE-treated cells, which showed increased
      PLTP expression and caspase-3 activity. PLTP knockdown with the specific siRNA
      partly suppressed the SCE-induced enhancement of caspase-3 activity in the cells.
      CONCLUSION: PLTP may play a role in CSE-induced apoptosis of rat alveolar cells
      in vitro.

PMID- 26198941
TI  - [Diagnostic value of quantitative low-dose dobutamine stress echocardiography
      with three-dimensional speckle-tracking for non-ST-elevation acute coronary
      syndrome].
AB  - OBJECTIVE: To access left ventricular global deformation abnormalities during low
      dose dobutamine stress test (DSE) by three-dimensional speckle-tracking
      echocardiography(3D-STE)in patients with non-ST-elevation acute coronary syndrome
      (NSTE-ACS), and explore the diagnostic value of 3D-STE combined with DES for NSTE
      ACS. METHODS: Forty-nine patients with suspected NSTE-ACS underwent DSE and
      coronary angiography with an initial dobutamine dose of 5 ug.kg(-1).min(-1),
      which was doubled at 3-min intervals to the peak dose of 20 ug.kg(-1).min(-1).
      The global longitudinal strain (GLS), global circumferential strain (GCS),
      territory longitudinal strain (TLS), and territory circumferential strain (TCS)
      of the left ventricular subendocardial myocardium were measured with 3D-STE at
      rest and at the peak-dose stage. Conventional echocardiography and 3D-STE
      parameters and their changes during DSE were evaluated, and their diagnostic
      values were analyzed according to the receiver-operating characteristic (ROC)
      curves. RESULTS: All the patients completed DSE uneventfully and 3D-STE showed a
      good reproducibility of the results. Compared with patients with non-NSTE-ACS,
      NSTE-ACS patients showed obviously reduced resting left ventricular global
      deformation function especially in terms of circumferential deformation (P<0.05);
      the ROC curves for the parameters were similar between the two groups (P>0.05).
      During DSE, the global deformation differences between the two groups further
      increased (P<0.01), and the diagnostic values of the peak-dose stage parameters
      were significantly greater than those of the resting parameters. ROC curves
      analysis showed that TLS and TCS at peak-dose stage had the highest diagnostic
      value for NSTE-ACS. CONCLUSION: 3D-STE combined with low-dose DSE is a safe and
      effective noninvasive technique for accessing and identifying NSTE-ACS, and DSE
      can significantly enhance the diagnostic value of 3D-STE.

PMID- 26198942
TI  - [Quantitative assessment of vasculature with DCE-MRI in nasopharyngeal carcinomas
      following radiotherapy and its value for efficacy evaluation].
AB  - OBJECTIVE: To study the changes in quantitative kinetic parameters in dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) during radiotherapy and
      their value for efficacy evaluation in patients with nasopharyngeal carcinoma
      (NPC). METHODS: Twenty-four patients with NPC that had been pathologically
      confirmed as poorly differentiated squamous cell carcinoma underwent conventional
      MRI and DCE-MRI scans 1-2 days before radiotherapy (Pre-RT), during radiotherapy
      (RT 50 Gy), and upon completion of radiotherapy (RT 70 Gy). Based on the two
      compartment model and using the arterial input function deconvolution technique,
      we calculated the quantitative kinetic parameters of DCE-MRI (K(trans), kep, and
      Ve) of the tumor tissues, examined the correlation between the tumor regression
      rate (RS0-50) and the parameters on Pre-RT and RT 50 Gy, and compared the
      parameters for RT 70 Gy among the groups with different prognosis. RESULTS: The
      K(trans) value of the tumor tissue decreased after radiotherapy and showed a
      significant difference between Pre-RT and RT 70 Gy, but not between Pre-RT and RT
      50 Gy. The kep value decreased and Ve value increased after radiotherapy. The
      tumor regression rate was found to be positively correlated with the K(trans)
      value for Pre-RT (P=0.005) but negatively with the K(trans) value for RT 50 Gy
      (P=0.001). During the follow-up for 3 years, 5 patients died and 3 patients had
      distant metastases. No statistical differences in K(trans), kep, or Ve were found
      between the groups with different prognosis. CONCLUSIONS: The kinetic parameters
      in DCE-MRI, which vary significantly during radiotherapy, allow monitoring of
      tumor angiogenesis and vascular permeability and quantitative assessment of
      treatment efficacy for NPC. K(trans) value for Pre-RT and RT 50 Gy can serve as
      an indicator for early efficacy assessment of radiotherapy and for treatment
      adjustment, but its relation with the long-term outcomes awaits further study.

PMID- 26198943
TI  - [Effect of ouabain on intracellular Ca(2+) concentration in rat vascular smooth
      muscle cells in vitro].
AB  - OBJECTIVE: To explore the effect of ouabain on intracellular Ca(2+) concentration
      ([Ca(2+)]i) in thoracic aorta vascular smooth muscle cells (VSMCs) in vitro.
      METHODS: Primary SD rat thoracic aorta VSMCs were cultured by tissue adherent
      method and identified by immunochemistry. The binding ability between ouabain and
      VSMCs was detected by autoradiography, and fluo 3-AM (a Ca(2+) fluorescent probe)
      was employed to investigate whether ouabain affected VSMCs within a short period
      of time. The effect of a truncated fragment of the sodium pump alpha2 subunit was
      assayed in antagonizing the effect of ouabain on [Ca(2+)]i in the VSMCs. RESULTS:
      Within the concentration range of 0.1-100 nmol/L, ouabain was found to dose
      dependently bind to the VSMCs. Different concentrations of ouabain (0-3200
      nmol/L) caused a transient, dose-dependent increase in [Ca(2+)]i in the VSMCs,
      which was antagonized by the application of the truncated fragment of sodium pump
      alpha2 subunit. CONCLUSIONS: Elevations in [Ca(2+)]i in the VSMCs can be the
      cytological basis of high ouabain-induced hypertension. The truncated fragment of
      the sodium pump alpha2 subunit can antagonize ouabain-induced increase of
      [Ca(2+)]i in the VSMCs, which provides a clue for understanding the pathogenesis
      of and devising a therapeutic strategy for high ouabain-induced hypertension.

PMID- 26198944
TI  - [Effects of acute hypervolemic hemodilution and intraoperative blood salvage on
      erythrocyte morphology and biomechanics].
AB  - OBJECTIVE: To investigate the effects of acute hypervolemic hemodilution (AHH)
      and intraoperative blood salvage (IOBS) on the morphology and biomechanics of
      erythrocytes using atomic force microscopy (AFM). METHODS: Blood samples were
      collected from 20 patients undergoing orthopedic surgery before operation (T1),
      immediately after AHH (T2), and after blood salvage (T3). AFM at nanometer
      resolution was used to examine the morphology and biomechanics of the collected
      erythrocytes. RESULTS: The blood samples collected at T1 showed a significantly
      lower ratio of heteromorphous erythrocytes than those collected at T2 and T3
      [(2.6?1.3)% vs (19.3?1.6)% and (17.6?1.4)%, P<0.05]. AFM revealed significant
      differences in the morphology and biomechanics of the single erythrocyte in
      salvaged blood and blood after AHH compared with those of venous blood.
      CONCLUSION: AHH and IOBS may cause significant changes in the morphology and
      biomechanics of erythrocytes in the salvaged blood.

PMID- 26198945
TI  - [Effect of platelet-derived growth factor-BB on rat corpus cavernosum smooth
      muscle cell proliferation, migration and phenotypic modulation].
AB  - OBJECTIVE: To study the effect of platelet-derived growth factor-BB (PDGFBBB) on
      rat corpus cavernosum smooth muscle (CCSM) cell proliferation, migration and
      phenotypic modulation and explore the underlying mechanisms. METHODS: Wistar rat
      CCSM cells were obtained through a modified tissue culture method and identified
      by immunofluorescence assay. The effect of PDGFBB on the proliferation of CCSM
      cells was investigated using a CCK-8 kit and the optimum PDGFBB concentration for
      cell treatment was determined. CCSM cells were treated with vehicle or PDGF-BB at
      the optimum concentration, and the cell migration was examined using scratch
      assay; the mRNA expression of the transcription factor myocardin and the
      contractile phenotype markers alphaSMA and SMMHC in CCSM cells were determined by
      qRT-PCR at 24 h and 48 h. The protein expression of myocardin in CCSM cells
      incubated with PDGFBB for 0, 24 and 48 h was examined by Western blotting.
      RESULT: In CCSM cell culture, 96.5%and 96% of the cells were positive for
      alphaSMA and smoothelin, respectively. PDGFBB at different concentrations
      markedly promoted the proliferation of CCSM cells; the optimum PDGFBB
      concentration for enhancing cell proliferation was 12.5 ng/mL, which induced the
      migration of CCSM cells and significantly reduced the mRNA expressions of
      myocardin, alphaSMA and SMMHC (P<0.01). Exposure to PDGFBB decreased the protein
      expression of myocardin as the exposure time extended (within 48 h). CONCLUSION:
      CCSM cells of a high purity can be obtained by the modified tissue culture
      method. PDGFBB can promote the proliferation and migration of CCSM cells and
      cause a phenotypic conversion from the contractile to the synthetic type possibly
      by down-regulating myocardin.

PMID- 26198946
TI  - [Factors affecting live birth sex ratio in assisted reproductive technology
      procedures].
AB  - OBJECTIVE: To study the factors that affect the sex ratio of live births in
      procedures of assisted reproductive technology (ART). METHODS: The clinical data
      were collected from 4348 IVF-ET/freeze-thawed embryo transfer cycles that led to
      the birth of 5606 babies of known gender between 2008 and 2014. We assessed the
      impact of maternal age, paternal age, insemination method, the type of embryo
      transferred, stage of embryo transferred, single and twin births, previous
      abortion following ART, and cause of infertility on the sex ratio of the live
      births. RESULTS: The total cohort included 3019 male and 2588 female babies, with
      a general sex ratio of 116:100. The sex ratio was 117:100 among singleton
      deliveries and 116:100 among twin deliveries. The sex ratio was 117:100 among the
      first births with ART treatment and 117:100 among the second births. For
      singleton deliveries, an advanced maternal age or paternal age was significantly
      correlated with an elevated sex ratio of births (58.4% vs 52.8%, P=0.012; 56.4%
      vs 52.3%, P=0.026), while ICSI was significantly correlated with a decreased sex
      ratio of births (45.7% vs 55.6%, P<0.001); for twin deliveries, none of the these
      factors was significantly correlated with the sex ratio of birth. For the first
      baby born after ART treatment, an advanced maternal age was significantly related
      to an increased sex ratio of births (57.4% vs 53.0%, P=0.009), while ICSI was
      significantly related to a decreased sex ratio of births (48.6% vs 55.4%,
      P=0.001); for the second baby born with ART treatment, none of these factors was
      significantly correlated with the sex ratio of birth. Univariate logistic
      regression analysis showed that the maternal age (OR:0.836, 95% CI 0.731-0.955,
      P<0.05) and insemination method (OR:1.151, 95% CI 1.027-1.289, P<0.05) were
      significantly related to the sex ratio of birth, but in multivariable logistic
      regression analysis, after controlling for compounding factors, none of these
      factors was identified as independent predictive factors for sex ratio of births.
      CONCLUSIONS: An advanced maternal age is related to a higher live birth sex
      ratio, while ICSI is related to a decreased percentage of male babies. For
      singleton deliveries, an advanced paternal age is related to a higher sex ratio
      of births.

PMID- 26198947
TI  - [Level set method reconciled with a dynamic weighting factor for B-mode
      ultrasound image segmentation].
AB  - OBJECTIVE: To modify the level set method for precise and fast segmentation of B
      type ultrasound image lesions. METHODS: Based on the best of region level set
      method, entropy in the information theory was introduced into image processing to
      define a dynamic weighting factor that responded to the gradient change of the
      local gray levels to evaluate the dynamic degree of driven force on each pixel on
      the contour to the target and background areas. The dynamic weighting factors
      were reconciled into the regional level set model and led the contour to deform
      and move during the iterations. As lesion segmentation was classified as local
      segmentation of a specific area, the calculation was restrained to the local
      sphere abide by the contour, which greatly reduced the calculation complex.
      RESULTS: Experiments on B-type ultrasound images showed improved results of the
      proposed method with a better accuracy and less time consumption compared with
      several current level set methods. CONCLUSION: Level set method reconciled with
      dynamic weighting factor allows a better evaluation of the lesion contour pixels,
      and the local calculation strategy results in an enhanced segmentation
      efficiency.

PMID- 26198948
TI  - [Expression of Ki-67 and estrogen receptor in the uterus of mice with autoimmune
      premature ovarian failure induced by peptide zona pellucida 3].
AB  - OBJECTIVE: To investigate the histomorphology and the expressions of the
      proliferation marker Ki-67 and estrogen receptor in the uterus of mice with
      autoimmune premature ovarian failure (POF) induced by zona pellucida 3 peptide
      (pZP3). METHODS: Autoimmune POP models were established in 20 female BALB/c mice
      (7-8 weeks old) by immunization with pZP3 and another 20 mice served as the
      control group. The POP models were verified by vaginal cytology, serum sex
      hormones, ovary histomorphology and ZP3 antibody immunohistochemistry. The
      histomorphology and expressions of Ki-67, estrogen receptor alpha and estrogen
      receptor beta in the uterus of the mice were detected. RESULTS: Autoimmune POP
      models were established successfully in 80% of the mice at 8 weeks after the
      immunization. Compared with those in the control group, the mice in the model
      group showed a smaller volume of the uterus, thinner endometrium and a reduced
      number of glands. The luminal epithelial cells, glandular epithelial cells and
      stromal cells in the uterus of the model mice all presented with a lower
      expression of Ki-67 than those in the control group, and Ki-67 translocation from
      the nuclei to the cytoplasm was found in the model group. The luminal epithelial
      cells, glandular epithelial cells and stromal cells showed positive ERalpha
      immunoreactivity in the model group but not in the control group. No obvious
      ERbeta expression was found in the uterus in either of the groups. CONCLUSION:
      pZP3 can induce autoimmune POP, cause suppressed proliferation of the endometrial
      epithelial cells and stromal cells, and reduce the cellular expression of ERalpha
      in the uterus of mice.

PMID- 26198949
TI  - [Effect of indomethacin on BCR/ABL-Wnt/beta-catenin pathway in K562 cells].
AB  - OBJECTIVE: To investigate the effect of indomethacin on the proliferation and
      Wnt/beta-catenin pathway in K562 cells. METHODS: The cell growth of K562 cells
      treated with different concentrations of indomethacin was assessed with MTT
      assay, and the colony-forming ability of the cells was evaluated by colony
      forming assay. The mRNA expressions of BCR/ABL and beta-catenin were detected by
      RT-PCR, and the protein expressions of pBCR/ABL, total BCR/ABL, beta-catenin,
      pGSK-3beta and c-myc were analyzed by Western blotting. RESULTS: Indomethacin
      significantly suppressed the growth and colony-forming ability of K562 cells in a
      dose-dependent manner. Indomethacin treatment dose-dependently decreased the
      protein level of pBCR/ABL and total BCR/ABL without affecting bcr-abl mRNA
      expressions. Compared with the control groups, indomethacin-treated cells showed
      obviously decreased mRNA and protein expressions of beta-catenin and decreased
      protein expressions of pGSK-3beta and c-myc. CONCLUSION: Indomethacin inhibits
      the proliferation of K562 cells by suppressing the activity of bcr-abl-Wnt/beta
      catenin pathway.

PMID- 26198950
TI  - [Prognostic value of syndecan binding protein in colorectal carcinoma].
AB  - OBJECTIVE: To analyze the clinical significance of syndecan binding protein
      (SDCBP) expression in human colorectal carcinoma (CRC) and its value in
      predicting the postoperative survival of the patients. METHODS: The follow-up
      data for 10 years were collected from 109 primary CRC patients with
      immunohistochemical data of SDCBP expression in the tumor tissues. The
      relationship between SDCBP expression and the clinical factors was analyzed, and
      survival analysis was performed using the Kaplan-Meier and Cox regression
      analysis models. RESULTS: SDCBP expression in CRC was significantly associated
      with the postoperative survival time (chi(2)=8.336, P=0.004) and lymph node
      metastasis (P=0.001) of the patients, but not with age, gender, depth of
      invasion, tissue differentiation or histological type of the tumor. Kaplan-Meier
      survival curves showed that the patients expression high levels of SDCBP in the
      CRC tissues had a significantly shorter postoperative mean survival time and a
      lower 7-year survival rate than those with low SDCBP expressions [52.300?6.508 vs
      86.184?5.358 months, (38.6?6.4)% vs (61.5?6.7)%; chi(2)=10.585, P=0.001].
      Multivariate Cox analysis revealed that a high expression of SDCBP (B=0.605,
      P=0.034) and lymph node metastasis (B=0.677, P=0.013) were the main factors
      related to death in CRC patients. CONCLUSION: SDCBP expression level can serve as
      an indicator for lymph node metastasis, TNM staging, and outcome prediction of
      CRC.

PMID- 26198951
TI  - [Preservation with high-pressure carbon monoxide better protects ex vivo rabbit
      heart function than conventional cardioplegic solution preservation].
AB  - OBJECTIVE: To investigate the protective effect of high-pressure carbon monoxide
      for preservation of ex vivo rabbit heart graft in comparison with the
      conventional HTK cardioplegic solution preservation. METHODS: Heart grafts
      isolated from 85 New Zealand rabbits were randomly divided into Naive group
      (n=5), HTK group (n=40) and CO group (n=40). The grafts underwent no preservation
      procedures in Naive group, preserved at 4 degrees celsius; in HTK cardioplegic
      solution in HTK group, and preserved at 4 degrees celsius; in a high-pressure
      tank (PO2: PCO=3200 hPa: 800 hPa) in CO group with Krebs-Henseleit solution
      perfusion but without cardioplegic solution. After preservation for 2, 4, 6, 8,
      10, 14, 18, and 24 h, 5 grafts from the two preservation groups were perfused for
      30 min with a modified Langendorff apparatus and examined for left ventricular
      systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), arrhythmia
      score (AS), myocardial ultrestructure, and cardiac enzyme profiles. RESULTS:
      After preservation for 6 to 24 h, the cardiac enzyme profiles and systolic and
      diastolic functions were significantly better in CO group than in HTK group, but
      these differences were not obvious between the two groups after graft
      preservation for 2 to 4 h. Significant changes in the myocardial ultrastructures
      occurred in the isolated hearts after a 24-h preservation in both CO and HTK
      groups, but the myocardial damages were milder in CO group. CONCLUSION:
      Preservation using high-pressure carbon monoxide can better protect isolated
      rabbit heart graft than the conventional HTK preservation approach especially for
      prolonged graft preservation.

PMID- 26198952
TI  - [Sphingosine kinase 1 promotes glioma cell proliferation under hypoxia via
      calcium signaling].
AB  - OBJECTIVE: To investigate the role of sphingosine kinase 1 (SphK1) in regulating
      the proliferation of hypoxia-exposed glioma cells in vitro and explore the
      possible molecular mechanisms. METHODS: Human glioblastoma U87MG cells was
      transfected with specific small interfering RNA (siRNA) constructs targeting
      SphK1, and the efficiency of SphK1 knockdown was validated by real-time PCR and
      Western blotting. The cells transfected with SphK1 siRNA and with a negative
      control siRNA were then exposed to 3% oxygen or 150 umol/L CoCl2 to induce
      hypoxia. The cell proliferation and cell cycle changes following the exposure
      were evaluated with the Cell Counting Kit-8 and flow cytometry, respectively, and
      the intracellular Ca(2+) changes were monitored using Flou-4/AM under an inverted
      laser scanning confocal microscope. RESULTS: SphK1 knockdown significantly
      reduced hypoxia-induced calcium reflux and suppressed the cell proliferation.
      Application of OAG, an activator of calcium channels, however, obviously enhanced
      the cell proliferation under hypoxia. CONCLUSION: SphK1 promotes the
      proliferation of glioma cells under hypoxia via regulating calcium signaling.

PMID- 26198953
TI  - [Association between polymorphisms in pigment epithelium-derived factor gene
      promoter region and non-alcoholic fatty liver disease in type 2 diabetes
      mellitus].
AB  - OBJECTIVE: To investigate the association of serum pigment epithelium-derived
      factor (PEDF) level and polymorphisms in PEDF gene promoter region -358G->A with
      non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes
      mellitus (T2DM) of Han Nationality in Fujian Province. METHODS: A total of 282
      T2DM patients with NAFLD (DM1 group) and 170 age- and gender-matched T2DM
      patients without NAFLD (DM2 group) were examined for PEDF gene SNP-358G->A
      polymorphisms using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). Serum pigment epithelium-derived factor(PEDF) level,
      fasting plasma glucose (FPG), fasting insulin (FINS) and glycosylated hemoglobin
      (HbA1c) were also measured. RESULTS: The patients in DM1 group showed a
      significantly higher mean level of serum PEDF than those in DM2 group (P<0.05).
      Logistic regression analysis revealed that PEDF level was an independent risk
      factor for NAFLD in T2DM. The frequencies of PEDF gene -358G->A genotypes (GG,
      GA, and AA) and alleles (G/A) differed significanly between DM1 and DM2 groups
      (P<0.05). In terms of PEDF gene SNP -358G->A alleles, the GA genotype carriers
      had a 2.032 times higher risk of developing NAFLD compared with the GG genotype
      carriers, and the risk increased to 2.068 times in the carriers of the A allele
      (GA and AA genotypes; P<0.05). CONCLUSION: Serum PEDF level is an independent
      risk factor of NAFLD in T2DM. Elevated serum PEDF level is a protective factor
      against insulin resistance. In T2DM patients, PEDF gene promoter region -358G->A
      polymorphism is associated with NAFLD, and the A allele contributes to an
      increased risk of NAFLD.

PMID- 26198954
TI  - [Lentivirus-mediated shRNA targeting ZNF217 suppresses cell growth, migration,
      and invasion of glioma cells in vitro].
AB  - OBJECTIVE: To explore the role of ZNF217 in regulating cell proliferation,
      migration and invasion in glioma cells. METHDOS: A lentivirus-mediated shRNA
      ZNF217 vector was infected into glioma U251 cells, and the interference
      efficiency was examined by Western blotting. MTT assay, flow cytometry, Transwell
      assay, and Boyden chamber assay were used to analyze the changes in cell
      proliferation, migration and invasion. Western blotting was used to detect the
      changes in ZNF217-related genes in the cells. RESULTS: shRNA-ZNF217 transfection
      significantly inhibited the expression of ZNF217 in U251 cells and suppressed the
      cell migration, invasion, growth, and cell cycle transition. ZNF217 knockdown
      downregulated the expression of pPI3, pAKT, C-Myc, and the mesenchyme biomarker N
      cadherin, and stimulated the expression of the epithelium biomarker E-cadherin.
      CONCLUSION: ZNF217 promotes cell migration, invasion, and growth by activating
      PI3K/AKT signal to upregulate C-Myc and by modulating the genes associated with
      epithelial-mesenchymal transition in glioma cells.

PMID- 26198955
TI  - [Preparation of a decellularized scaffold derived from human liver tissue].
AB  - OBJECTIVE: To develop a method for preparing a decellularized scaffold based on
      human liver tissue. METHODS: A surgical specimen of the left lateral lobe of the
      liver was obtained from a patients with hepatic hemangioma. The decellularization
      process was performed by repeated freezing-thawing, sequential perfusion with
      0.01% SDS, 0.1% SDS and 1% Triton X-100 through the portal vein, and
      sterilization with peracetic acid. L-02 cells were then engrafted onto the
      decellularized liver scaffold. RESULTS: HE staining, DAPI staining and scanning
      electron microscopy all verified the absence of residual cellular components in
      the decellularized scaffold. The residual DNA content in the decellularized
      scaffolds was 25.3?14.6 ng/mg (dry weight), which was less than 1% of the total
      DNA content in a fresh human liver. Immunohistochemistry demonstrated that type I
      and IV collagens, fibronectin and elastin were all retained in the scaffold. The
      engrafted L-02 cells survived well on the scaffold with active proliferation and
      expressed albumin and G6pc. CONCLUSION: It is feasible to prepare decellularized
      scaffolds using surgical specimens of human liver, which can be a new approach to
      constructing a tissue-engineered liver for clinical purposes.

PMID- 26198956
TI  - [Super-resolution reconstruction of lung 4D-CT images based on fast sub-pixel
      motion estimation].
AB  - Super-resolution image reconstruction techniques play an important role for
      improving image resolution of lung 4D-CT. We presents a super-resolution approach
      based on fast sub-pixel motion estimation to reconstruct lung 4D-CT images. A
      fast sub-pixel motion estimation method was used to estimate the deformation
      fields between "frames", and then iterative back projection (IBP) algorithm was
      employed to reconstruct high-resolution images. Experimental results showed that
      compared with traditional interpolation method and super-resolution
      reconstruction algorithm based on full search motion estimation, the proposed
      method produced clearer images with significantly enhanced image structure
      details and reduced time for computation. 

PMID- 26198957
TI  - [Clinical evaluation of the consistency between two diagnostic criteria for
      diabetic peripheral neuropathy].
AB  - OBJECTIVE: To evaluate the consistency between the clinical diagnostic criteria
      and the ascertained diagnostic criteria for diabetic peripheral neuropathy (DPN)
      in the Preventive and Treatment Guidelines of Diabetes in China (2013) and
      explore an economic, convenient, and accurate approach to DPN diagnosis. METHODS:
      The patients with type 2 diabetes admitted in our department from April to June,
      2014 were examined for nerve conduction velocity, 10 g nylon silk, vibration
      threshold value, sense of temperature and pain, and ankle reflex. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      Youden index, and Kappa value were calculated to assess the diagnostic power of
      the two diagnostic criteria. RESULTS: Of the 151 patients enrolled, 106 (70.2%)
      had a diagnosis of DPN consistent with the ascertained diagnostic criteria, as
      compared to 86 (56.95%) who were diagnosed according to the clinical diagnostic
      criteria; the latter patients accounted for 81.13% of former cases. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      Youden index, and Kappa value of the clinical diagnostic criteria were 80.19%,
      97.78%, 98.84%, 67.69%, 77.97%, and 0.69, respectively, which were highly
      consistent with those of the ascertained diagnostic criteria; the sensitivity to
      compression showed a poor consistency between the two diagnostic criteria. In the
      5 screening tests, the combined test of temperature sensation, vibration
      perception, and ankle reflex showed the highest AUC value among their different
      combinations. CONCLUSION: The clinical diagnostic criteria for DPN show good
      consistency with the ascertained diagnostic criteria, and for patients with
      clinical symptoms or with only one positive sign, combination of the two
      diagnostic criteria can achieve the maximum diagnostic power.

PMID- 26198958
TI  - [Cataract surgery and intraocular lens power calculation after radial keratotomy:
      analysis of 8 cases].
AB  - OBJECTIVE: To explore the clinical characteristics of cataract surgery after
      radial keratotomy (RK) and appropriate calculation of intraocular lens (IOL)
      power. METHODS: Eight patients with cataract (12 eyes) after RK were treated in
      our hospital from March, 2010 to June, 2013. The visual acuity, keratometric
      power and length of the ocular axis were examined before the operation. For each
      patient, 3 groups of corneal curvature values were measured using a automatic
      keratometer (TOPCON-KR8800) and the minimal K value was selected. Myopic or
      hyperopic posterior chamber IOL (-1.00 to -2.00 D) were selected based on
      automatic calculations with SRK-T. Phacoemulsification and IOL implantation were
      then performed, and the patients were followed up for visual acuity and
      refractive statuses at 3 months after the operation. RESULTS: All the 12 operated
      eyes showed improved visual acuity after the operation. The uncorrected visual
      acuity reached 0.8 to 1.0 in 6 eyes and 0.4 to 0.6+ in the other 6, with a
      corrected visual acuity ranging from 0.6 to 1.0. The refractive status after
      operations was nearly emmetropic (+0.75 to -1.00 D) in 6 eyes and myopic in the
      other 6 (-1.00 to -2.50 D). CONCLUSIONS: Phacoemulsification and IOL implantation
      is feasible in cataract patients with previous RK. Selecting the minimal K values
      for central corneal curvature and calculation of the IOL power using the SRK T
      equation with a reservation of -1.00 to -2.00 D can better ensure the safety of
      the procedure and avoid the occurrence of hyperopia >+3.00D.

PMID- 26198959
TI  - [Effects of continuous blood purification on extravascular lung water and
      respiratory function in patients with extrapulmonary acute respiratory distress
      syndrome].
AB  - OBJECTIVE: To assess the effects of continuous blood purification (CBP) on
      extravascular lung water and respiratory function in patients with extrapulmonary
      acute respiratory distress syndrome (ARDSexp). METHODS: The data of 31 patients
      with ARDSexp admitted in our department were retrospectively analyzed.Sixteen of
      the patients received CBP, and the other 15 patients did not (control group). The
      level of extravascular lung water index (EVLWI), pulmonary vascular permeability
      index (PVPI), and respiratory function were measured before and after CPB.
      RESULTS: The mortality rate was significantly lower in CBP group than in the
      control group (12.5% vs 33.3%, P<0.05). The patients in CPB group showed markedly
      earlier and significantly greater improvements in EVLWI, PVPI, PaO2/FiO, and
      respiratory function than the control patients (P<0.05). CONCLUSION: CBP can
      reduce EVLWI and PVPI, improve pulmonary compliance and oxygenation, and reduce
      mortality rate in patients with ARDSexp.

PMID- 26198960
TI  - [Value of serum beta-human chorionic gonadotropin on day 9 and 11 after embryo
      transfer in predicting pregnancy outcomes].
AB  - OBJECTIVE: To investigate the value of serum beta-human chorionic gonadotropin
      (beta-HCG) on days 9 (d9) and 11 (d11) after fresh embryo transfer (ET) and
      frozen-thawed embryo transfer (FET) in predicting the pregnancy outcomes.
      METHODS: A total of 227 fresh ET and FET cycles performed at the Center of
      Reproductive Medicine, Qingyuan People's Hospital between Dec, 2012 and Feb, 2014
      were analyzed. The data of serum beta-HCG levels on d9 and d11 after fresh ET and
      FET cycles and the pregnancy outcomes were reviewed, and the ROC curve was
      constructed to determine the optimal cut-off level of serum beta-HCG level for
      predicting pregnancy outcomes. RESULTS: According to pregnancy outcomes, the
      cycles were divided into non-pregnancy group (group A), biochemical pregnancy
      group (group B), and clinical pregnancy group (group C). Significant differences
      were found between the mean serum beta-HCG levels measured on d9 and d11 in all
      the 3 groups (P<0.01). The cycles in group C were further divided into 5
      subgroups with single pregnancy (C1), twin pregnancy (C2), early abortion (C3),
      ectopic pregnancy (C4), or intrauterine pregnancy complicated with ectopic
      pregnancy group (C5), and all the 5 subgroups showed significant differences in
      beta-HCG measurements between d9 and d11 (P<0.01). On d9 after ET and FET, the
      optimal cut-off level of serum beta-HCG was 49.05 IU/L for predicting for
      clinical pregnancy, and was 105.15 IU/L for predicting twin pregnancy; the two
      corresponding cut-off levels of serum beta-HCG on d11 was 51.2 IU/L and 241.75
      IU/L, respectively. CONCLUSION: The absolute serum beta-HCG level on d9 and d11
      after fresh ET and FET allows an accurate diagnosis of pregnancy and helps in the
      prediction of the pregnancy outcomes.

PMID- 26198961
TI  - [Correlation of serum cystatin C with blood pressure: a cross-sectional study of
      912 subjects].
AB  - OBJECTIVE: To study the association between serum cystatin C level and blood
      pressure. METHODS: We conducted a cross-sectional study of 912 subjects randomly
      sampled from a cohort visiting for routine physical examinations. The
      epidemiological data were obtained using questionnaires and from the database of
      physical examination results. Pearson analysis and multiple stepwise regression
      analysis were used to analyze the relationship between blood pressure and
      cystatin C. RESULTS: The levels of serum cystatin C differed significantly among
      the normotensive, prehypertensive, and hypertensive subjects (P<0.05). Pearson
      analysis revealed that regardless of gender, serum cystatin C was positively
      correlated with SBP, DBP, MAP, BMI, TC, TG, LDL-C, UA and BUN (P<0.05). With MAP,
      SBP and DBP as dependent variables, multiple stepwise regression analysis of the
      factors affecting blood pressure indicated that cystatin C had the strongest
      effect on SBP and MAP (P<0.05) but did not significantly affect DBP (P>0.05).
      CONCLUSION: Serum cystatin C level is significantly correlated with SBP and MAP
      and can be used as a biomarker for alert of hypertension.

PMID- 26198962
TI  - [Serum marker screening during the second trimester for prenatal diagnosis and
      predicting pregnancy outcome].
AB  - OBJECTIVE: To explore the clinical value of screening the serum markers during
      the second trimester of pregnancy in preventing congenital birth defect and
      predicting the pregnancy outcome. METHODS: Between November, 2011 and October,
      2013, a total of 25 520 pregnant women (15-20+6 gestational weeks) underwent a
      screening test of triple serum markers including free beta-human chorionic
      gonadotrophin (free betahCG), alpha-fetoprotein (AFP), and unconjugated estriol
      (uE3) during the second semester of pregnancy. The women identified by the
      screening test as having high risks were referred to invasive prenatal diagnosis
      by amniocentesis, or to color Doppler ultrasound examination for suspected patent
      neural tube defect (NTD), and their pregnancy outcomes were followed up. RESULTS:
      High-risk pregnancies were identified by the screening test in 4.91% (1254/25520)
      of the total cohort. Of the 818 patients receiving invasive prenatal diagnosis,
      the abnormal rate was 5.75% (47/818). The high-risk pregnancies identified by the
      screening test was associated with a significantly higher rate of abnormal
      outcomes compared with the low-risk pregnancies (1.91% vs 0.1%, P<0.01). Of the
      210 high-risk cases of NTD, a definite diagnosis was established in 34 cases. We
      also found that pregnancies at an advanced age (>35 years) was associated with
      increased risks for trisomy 21 compared with those at younger ages (15% vs
      1.65%P<0.01). The detection rate of abnormal karyotypes in pregnancies with an
      abnormal MoM value of a single marker was 3.17% (6/189). CONCLUSION: Screening
      tests of serum markers during the second trimester of pregnancy can be helpful to
      identify fetal chromosomal and anatomical anomalies, predict unfavorable
      pregnancy outcomes, and prevent birth defects in pregnancies at an advanced age.
      The MoM value of a single marker in the second trimester can be indicative of
      potential chromosomal abnormalities.

PMID- 26198963
TI  - [Expression of SFRP4 and DKK1 in cervical squamous cell carcinoma and the
      clinicopathological implications].
AB  - OBJECTIVE: To investigate the expression of SFRP4 and DKK1 in cervical squamous
      cell carcinoma and explore the clinicopathological implications. METHODS:
      Immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR)
      were used to detect the expressions of SFRP4 and DKK1 in 66 cervical squamous
      cell carcinoma and 26 normal cervical specimens. RESULTS: SFRP4 expression was
      significantly higher (P<0.01) and DKK1 expression was significantly lower
      (P<0.05) in the carcinoma tissues than in normal cervical tissues. DKK1 was
      negatively correlated with SFRP4 in the carcinoma tissues (P<0.01), and their
      expressions were associated with the clinical stages, tumor differentiation,
      depth of invasion and lymph node metastasis of the tumors (P<0.05). CONCLUSION:
      SFRP4 and DKK1, the upstream components of the Wnt pathway, play a key role in
      the tumorigenesis of cervical squamous cell carcinoma, and their expressions are
      associated with the clinicopathological features of the malignancy.

PMID- 26198964
TI  - [Quercetin protects against lipopolysaccharide-induced cardiac injury in mice].
AB  - OBJECTIVE: To evaluate the protective effect of quercetin against
      lipopolysaccharide (LPS)-induced cardiac injury in mice. METHODS: C57BL/6J mice
      were randomized into 4 groups to receive intraperitoneal injection of saline
      (negative control) or LPS (20 mg/kg), or fed with quercetin (100 mg/kg for 7
      days) with or without subsequent LPS injection (quercetin+LPS group and quercetin
      control group, respectively). Six hour after LPS injection, the mice were tested
      for cardiac function with an echocardiograph, and the protein expressions of Bax,
      Bcl-2, iNOS, and eNOS in the myocardium were evaluated with Western blotting;
      serum NO concentration was also measured. The survival of the mice within 5 days
      after LPS injection was recorded to draw the survival curve. RESULTS: Quercetin
      pretreatment significantly improved the cardiac function of LPS-challenged mice
      (P<0.05), and attenuated LPS-induced increment in myocardial iNOS expression and
      decrement in eNOS level. LPS significantly increased the myocardial Bax
      expression and slightly decreased Bcl-2 expression; quercetin pretreatment
      decreased Bax expression to the control level and significantly lowered Bax/Bcl-2
      ratio as compared with the LPS group. Serum NO level was significantly increased
      by nearly 2.5 folds in LPS-challenged mice, but was markedly decreased with
      quercetin pretreatment (P<0.05). The 5-day survival rate of LPS-treated mice was
      10%, which was increased to 45% in quercetin- pretreated mice (P<0.05).
      CONCLUSION: Quercetin can alleviate LPS-induced cardiac dysfunctions in mice to
      increase their survival rate following LPS challenge.

PMID- 26198965
TI  - [Anti-miR-145 promotes human airway smooth muscle cell proliferation and
      osteopontin synthesis in vitro].
AB  - OBJECTIVE: To investigate the effect of anti-miR-145 on human airway smooth
      muscle cell (HASMC) proliferation and osteopontin systhesis in vitro and explore
      the mechanisms. METHODS: HASMCs were treated with 10-100 nmol/L anti-miR-145, and
      the cell proliferation and apoptosis were investigated using a CCK-8 assay and
      flow cytometry, respectively. The changes in osteopontin synthesis after the
      treatment was quantified with Western blotting. RESULTS: Treatment with 10 and 50
      nmol/L anti-miR-145 significantly promoted the proliferation and osteopontin
      synthesis in HASMCs (P<0.05 or <0.01), and 50 nmol/L anti-miR-145 obviously
      inhibited the cell apoptosis (P<0.01). CONCLUSION: Anti-miR-145 promotes HASMC
      proliferation and osteopontin synthesis and inhibits HASMC apoptosis in vitro,
      indicating the important role of anti-miR-145 in the pathogenesis of airway
      remodeling.

PMID- 26198966
TI  - [Effects of small-dose lidocaine combined with ketamine on early postoperative
      cognitive function in elderly patients undergoing gastrointestinal tumor
      surgery].
AB  - OBJECTIVE: To observe the effects of anesthetic intervention with small-dose
      lidocaine and ketamine on early postoperative cognitive function in elderly
      patients undergoing surgeries for gastrointestinal tumors. METHODS: Sixty
      patients (ASA I-III, aged 63-82 years) scheduled for surgeries for
      gastrointestinal tumors were randomized into intervention group (n=30) and
      control group (n=30). After intravenous induction and tracheal intubation, the
      patients in the interventional group received intravenous infusion of 0.5 mg/kg
      lidocaine and 0.5 mg/kg ketamine, followed by continuous infusion of lidocaine at
      the rate of 0.5 mg.kg(-1).h(-1) till the end of the operation; the patients in
      the control group received saline infusion only. The cognitive function of the
      patients was assessed at 3 day before and 2 day after the operation using
      comprehensive neuro-psychological tests. Peripheral venous blood was extracted
      before anesthesia induction (T0), at the end of the surgery (T1), and at 1 day
      (T2) and 2 days (T3) after the operation for measurement of serum S-100beta
      protein, NSE and IL-6 levels using ELISA. RESULTS: The difference between the
      test scores before and after the operation (X values) was significantly smaller
      in the intervention group than in the control group (P<0.05). The intervention
      group showed a significantly lower incidence rate of postoperative cognitive
      dysfunction (POCD) than the control group (6.7% vs 33.3%, P<0.05). Compared with
      the control group, the intervention group exhibited significantly lower serum
      levels of S-100beta protein, NSE and IL-6 at T1 (P<0.05), significantly lower NSE
      and IL-6 levels at T2 (P<0.05) time point, and significantly lower IL-6 level at
      T3 (P<0.05). CONCLUSION: Intravenous injection of small-dose lidocaine and
      ketamine during the operation can reduce the incidence of POCD in elderly
      patients undergoing surgeries for gastrointestinal tumors possibly in relation to
      decreased serum S-100beta, NSE and IL-6 levels.

PMID- 26198967
TI  - Striking differences in estimates of infant adiposity by new and old DXA
      software, PEAPOD and skin-folds at 2 weeks and 1 year of life.
AB  - BACKGROUND: Infant adiposity better predicts childhood obesity/metabolic risk
      than weight, but technical challenges fuel controversy over the accuracy of
      adiposity estimates. OBJECTIVE: We prospectively measured adiposity (%fat) in
      term newborns (NB) at 2 weeks (n = 41) and 1 year (n = 30). METHODS: %fat was
      measured by dual X-ray absorptiometry (DXA), PEAPOD and skin-folds (SF). DXAs
      were analyzed using Hologic Apex software 3.2(DXAv1) and a new version
      5.5.2(DXAv2). RESULTS: NB %fat by DXAv2 was 55% higher than DXAv1 (14.2% vs.
      9.1%), 45% higher than SF (9.8%), and 36% higher than PEAPOD (10.4%). Among NB,
      Pearson correlations were 0.73-0.89, but agreement (intra-class correlations)
      poor between DXAv2 and DXAv1 (0.527), SF (0.354) and PEAPOD (0.618). At 1 year,
      %fat by DXAv2 was 51% higher than DXAv1 (33.6% vs. 22.4%), and twice as high
      compared with SF (14.6%). Agreement was poor between DXAv2 and DXAv1 (0.204), and
      SF (0.038). The absolute increase in %fat from 2 weeks to 1 year was 19.7%
      (DXAv2), 13.6% (DXAv1) and only 4.8% by SF. CONCLUSION: Analysis of the same DXA
      scans using new software yielded considerably higher adiposity estimates at birth
      and 1 year compared with the previous version. Using different modalities to
      assess body composition longitudinally is problematic. Standardization is gravely
      needed to determine how early life exposures affect childhood obesity/metabolic
      risk.

PMID- 26198968
TI  - Recurrent laryngeal nerve safety parameters of the Harmonic Focus during thyroid
      surgery: Porcine model using continuous monitoring.
AB  - OBJECTIVES/HYPOTHESIS: The Harmonic Focus (HF) is one of the most popular energy
      based devices. The aim of this study was to provide recurrent laryngeal nerve
      (RLN) functional data that define the safety parameters of the HF during
      thyroidectomy. STUDY DESIGN: Prospective porcine model using continuous
      electrophysiologic monitoring. METHODS: Ten piglets were used. At varying
      distances from the RLN, the HF was activated (activation study). The HF was also
      applied directly on the RLN after activation on sternocleidomastoid muscle for 10
      seconds with different cooling times (cooling study). RESULTS: In the activation
      study, there was no adverse electromyography (EMG) event at more than 1 mm
      distance. In the cooling study, there was no adverse EMG event after a 10-second
      cooling period. When the HF was cooled on the sternocleidomastoid muscle, there
      was no adverse EMG event after 2 seconds cooling time. CONCLUSIONS: The safe
      distance of the HF was 1 mm, and it should be cooled for more than 10 seconds or
      2 seconds after cooling on muscle. The HF should be used in a standardized manner
      to avoid RLN injury. LEVEL OF EVIDENCE: NA.

PMID- 26198969
TI  - The quality of cholecystectomy in Denmark has improved over 6-year period.
AB  - PURPOSE: The Danish Cholecystectomy Database (DCD) was a nationwide quality
      database that existed from 2006 to 2011. The main goal (indicators) for the
      database was to increase the quality of cholecystectomy in Denmark by (1)
      reducing the number of primary open cholecystectomies, (2) increasing the
      proportion of outpatient surgery, (3) reducing the number of postoperative
      readmissions, and (4) reducing the number of bile duct injuries and other
      postoperative complications. The purpose of this study was to evaluate whether
      the DCD met these goals. METHODS: Data from the DCD were used to identify all
      patients treated with cholecystectomy in the period from 2006 to 2011. The
      indicators were analyzed over time as a measure of quality of cholecystectomy and
      analyzed using chi-square statistics. RESULTS: A total of 37,317 patients were
      included in the study. The registration rate in the DCD was around 90 %, except
      in 2011 where it was 70.7 %. The proportion of open cholecystectomies decreased
      from 2.6 % in 2006 to 0.9 % in 2011 (p < 0.0005). Likewise, in 2011, 80 % of
      patients undergoing cholecystectomy were discharged within 24 h, an increase
      compared to 2006 (p < 0.0005). The proportion of readmissions remained steady in
      the area of 10 % (p = 0.6). Bile duct injuries were low (0.3 %) and unchanged
      during the study period. CONCLUSION: During the observed 6-year period, a
      significant increase of laparoscopic procedures was observed with more operations
      being performed as outpatient procedures. The proportion of readmissions and
      complications did not increase during this time period.

PMID- 26198971
TI  - Mechanoluminescence properties of SrAl2O4:Eu(2+) phosphor by combustion
      synthesis.
AB  - In this paper, europium-doped strontium aluminate (SrAl2O4:Eu(2+)) phosphors were
      synthesized using a combustion method with urea as a fuel at 600 degrees C. The
      phase structure, particle size, surface morphology and elemental analysis were
      studied using X-ray diffractometry (XRD), transmission electron microscopy (TEM),
      energy-dispersive X-ray spectroscopy (EDX) and Fourier transform infrared (FTIR)
      spectra. The EDX and FTIR spectra confirm the elements present in the
      SrAl2O4:Eu(2+) phosphor. The optical properties of SrAl2O4:Eu(2+) phosphors were
      investigated by photoluminescence (PL) and mechanoluminescence (ML). The
      excitation and emission spectra showed a broad band with peaks at 337 and 515 nm,
      respectively. The ML intensities of SrAl2O4:Eu(2+) phosphor increased
      proportionally with the increase in the height of the mechanical load, which
      suggests that this phosphor could be used in stress sensors. The CIE colour
      chromaticity diagram and ML spectra confirm that the SrAl2O4:Eu(2+) phosphor
      emitted green coloured light.

PMID- 26198970
TI  - Palliative resection of the primary tumor in 442 metastasized neuroendocrine
      tumors of the pancreas: a population-based, propensity score-matched survival
      analysis.
AB  - PURPOSE: There is an ongoing debate on whether palliative removal of the primary
      tumor may result in a survival benefit for patients with incurable stage IV
      pancreatic neuroendocrine tumors (P-NET). The objective of this study was to
      assess whether palliative resection of the primary tumor in patients with
      incurable stage IV P-NET has an impact on survival. METHODS: Patients with stage
      IV P-NET registered in the Surveillance, Epidemiology, and End Results database
      between 2004 and 2011 were identified. Those undergoing resection of metastases
      were excluded. Overall and cancer-specific survival of patients who did and did
      not undergo resection of their primary tumor were compared by means of risk
      adjusted Cox proportional hazard regression analysis and propensity score-matched
      analysis. RESULTS: A total of 442 stage IV P-NET patients were identified, of
      whom 75 (17.0 %) underwent palliative primary tumor resection. The latter showed
      a significant benefit in both overall survival (hazard ratio [HR] of death =
      0.41, 95 % confidence interval [CI] 0.25-0.66, p < 0.001) and cancer-specific
      survival (HR of death = 0.41, 95 % CI 0.25-0.67, p < 0.001) in unadjusted
      multivariate Cox regression analysis; the benefit persisted after propensity
      score adjustment. CONCLUSIONS: This population-based analysis of stage IV P-NET
      patients provides compelling evidence that palliative resection of the primary
      tumor is associated with significant survival benefit. Thus, the recent
      recommendations judging resection of the primary as inadvisable and the
      accompanying trend towards fewer palliative resections of the primary tumor have
      to be contested.

PMID- 26198972
TI  - Sol-gel encapsulation of binary Zn(II) compounds in silica nanoparticles.
      Structure-activity correlations in hybrid materials targeting Zn(II)
      antibacterial use.
AB  - In the emerging issue of enhanced multi-resistant properties in infectious
      pathogens, new nanomaterials with optimally efficient antibacterial activity and
      lower toxicity than other species attract considerable research interest. In an
      effort to develop such efficient antibacterials, we a) synthesized acid-catalyzed
      silica-gel matrices, b) evaluated the suitability of these matrices as potential
      carrier materials for controlled release of ZnSO4 and a new Zn(II) binary complex
      with a suitably designed well-defined Schiff base, and c) investigated structural
      and textural properties of the nanomaterials. Physicochemical characterization of
      the (empty-loaded) silica-nanoparticles led to an optimized material
      configuration linked to the delivery of the encapsulated antibacterial zinc load.
      Entrapment and drug release studies showed the competence of hybrid nanoparticles
      with respect to the a) zinc loading capacity, b) congruence with zinc
      physicochemical attributes, and c) release profile of their zinc load. The
      material antimicrobial properties were demonstrated against Gram-positive
      (Staphylococcus aureus, Bacillus subtilis, Bacillus cereus) and negative
      (Escherichia coli, Pseudomonas aeruginosa, Xanthomonas campestris) bacteria using
      modified agar diffusion methods. ZnSO4 showed less extensive antimicrobial
      behavior compared to Zn(II)-Schiff, implying that the Zn(II)-bound ligand
      enhances zinc antimicrobial properties. All zinc-loaded nanoparticles were less
      antimicrobially active than zinc compounds alone, as encapsulation controls their
      release, thereby attenuating their antimicrobial activity. To this end, as the
      amount of loaded zinc increases, the antimicrobial behavior of the nano-agent
      improves. Collectively, for the first time, sol-gel zinc-loaded silica
      nanoparticles were shown to exhibit well-defined antimicrobial activity,
      justifying due attention to further development of antibacterial nanotechnology. 

PMID- 26198973
TI  - Childhood maltreatment and adult mental health.
AB  - BACKGROUND: The relationship between reported childhood maltreatment and general
      psychological and post-traumatic distress was examined in a sample of 551 adults
      from different risk samples. AIMS: Exposure to childhood maltreatment was
      assessed using the Childhood Trauma Questionnaire Short Form, which detects
      physical, emotional and sexual abuse and past physical and emotional neglect.
      METHODS: The participants' current levels of post-traumatic stress symptoms and
      general psychological stress symptoms were measured with the Impact of Event
      Scale - Revised and the Symptom Checklist 90 - Revised, respectively. RESULTS:
      The results reveal a high prevalence of reported childhood maltreatment in both
      men and women, and the severity levels of the five types of childhood
      maltreatment showed significant associations with the extent of current post
      traumatic and general psychological distress. CONCLUSION: The findings emphasize
      the need for appropriate procedures for identifying childhood maltreatment.

PMID- 26198974
TI  - Combined crystal structure prediction and high-pressure crystallization in
      rational pharmaceutical polymorph screening.
AB  - Organic molecules, such as pharmaceuticals, agro-chemicals and pigments,
      frequently form several crystal polymorphs with different physicochemical
      properties. Finding polymorphs has long been a purely experimental game of trial
      and-error. Here we utilize in silico polymorph screening in combination with
      rationally planned crystallization experiments to study the polymorphism of the
      pharmaceutical compound Dalcetrapib, with 10 torsional degrees of freedom one of
      the most flexible molecules ever studied computationally. The experimental
      crystal polymorphs are found at the bottom of the calculated lattice energy
      landscape, and two predicted structures are identified as candidates for a
      missing, thermodynamically more stable polymorph. Pressure-dependent stability
      calculations suggested high pressure as a means to bring these polymorphs into
      existence. Subsequently, one of them could indeed be crystallized in the 0.02 to
      0.50 GPa pressure range and was found to be metastable at ambient pressure,
      effectively derisking the appearance of a more stable polymorph during late-stage
      development of Dalcetrapib. 

PMID- 26198975
TI  - Digital mammography versus digital breast tomosynthesis for detection of breast
      cancer in the intraoperative specimen during breast-conserving surgery.
AB  - PURPOSE: To compare the diagnostic ability of specimen radiography using digital
      mammography (DM) and digital breast tomosynthesis (DBT) for detecting breast
      cancer and evaluating its extension in the intraoperative specimen. METHODS:
      Sixty-five specimens from 65 women (median 62 years; range 34-86) obtained during
      breast-conserving surgery were prospectively investigated. Specimens underwent DM
      (25-40 kVp, 12-322 mA s) and DBT (25-34 kVp, 13-137 mA) in two orthogonal planes,
      anteroposterior (AP) and latero-lateral (LL). Images were interpreted by a
      radiologist to detect invasive lesions and their extensive intraductal components
      (EIC) or ductal carcinomas in situ (DCIS); afterwards, they were compared with
      histopathological findings. RESULTS: In AP views, 96 % of the invasive lesions
      were detected by both the methods. Of the EICs, 55 and 65 % were detected by DM
      and DBT, respectively (P = 0.61). Of the DICSs, 31 and 38 % were detected by DM
      and DBT, respectively (P > 0.99). In LL views, 71 and 13 % of the invasive
      lesions were detected by DBT and DM, respectively (P < 0.0001). Of the EICs, 42
      and 10 % were detected by DBT and DM, respectively (P = 0.0078). Of the 13 DCISs,
      42 and 8 % were detected by DBT and DM, respectively (P = 0.32). The whole lesion
      and contour could be delineated in 45 % by DBT and in 6.2 % by DM (P < 0.0001).
      CONCLUSIONS: DBT could detect breast cancer more accurately than DM in LL views,
      indicating its potential to more precisely diagnose vertical invasion.

PMID- 26198976
TI  - Regional Contrasts of the Warming Rate over Land Significantly Depend on the
      Calculation Methods of Mean Air Temperature.
AB  - Global analyses of surface mean air temperature (T(m)) are key datasets for
      climate change studies and provide fundamental evidences for global warming.
      However, the causes of regional contrasts in the warming rate revealed by such
      datasets, i.e., enhanced warming rates over the northern high latitudes and the
      "warming hole" over the central U.S., are still under debate. Here we show these
      regional contrasts depend on the calculation methods of T(m). Existing global
      analyses calculate T(m) from daily minimum and maximum temperatures (T2). We
      found that T2 has a significant standard deviation error of 0.23  degrees
      C/decade in depicting the regional warming rate from 2000 to 2013 but can be
      reduced by two-thirds using T(m) calculated from observations at four specific
      times (T4), which samples diurnal cycle of land surface air temperature more
      often. From 1973 to 1997, compared with T4, T2 significantly underestimated the
      warming rate over the central U.S. and overestimated the warming rate over the
      northern high latitudes. The ratio of the warming rate over China to that over
      the U.S. reduces from 2.3 by T2 to 1.4 by T4. This study shows that the studies
      of regional warming can be substantially improved by T4 instead of T2.

PMID- 26198978
TI  - The management of oral epithelial dysplasia: The Liverpool algorithm.

PMID- 26198979
TI  - Dental demineralization and caries in patients with head and neck cancer.
AB  - Concurrent chemoradiation (CCR) therapy is a standard treatment for patients with
      locally advanced head and neck cancer (HNC). It is well documented that CCR
      causes profound acute and late toxicities. Xerostomia (the symptom of dry mouth)
      and hyposalivation (decreased salivary flow) are among the most common treatment
      side effects in this cohort of patients during and following treatment. They are
      the result of radiation-induced damage to the salivary glands. Patients with
      chronic hyposalivation are at risk for demineralization and dental cavitation
      (dental caries), often presenting as a severe form of rapidly developing decay
      that results in loss of dentition. Usual post-radiation oral care which includes
      the use of fluoride, may decrease, but does not eliminate dental caries
      associated with radiation-induced hyposalivation. The authors conducted a
      narrative literature review regarding dental caries in HNC population based on
      MEDLINE, PubMed, CLNAHL, Cochrane database, EMBASE, and PsycINFO from 1985 to
      2014. Primary search terms included head and/or neck cancer, dental caries,
      dental decay, risk factor, physical symptom, physical sequellea, body image,
      quality of life, measurement, assessment, cost, prevention, and treatment. The
      authors also reviewed information from National Institute of Dental and
      Craniofacial Research (NIDCR), American Dental Association (ADA), and other
      related healthcare professional association web sites. This literature review
      focuses on critical issues related to dental caries in patients with HNC:
      potential mechanisms and contributing factors, clinical assessment, physical
      sequellea, negative impact on body image and quality of life, potential
      preventative strategies, and recommendations for practice and research in this
      area. 

PMID- 26198980
TI  - Relationship of polar bodies morphology to embryo quality and pregnancy outcome.
AB  - The aim of this study was to explore whether the morphology of polar bodies (PBs)
      estimated at 16-18 h after insemination can be used as an additional marker for
      predicting human embryo quality or pregnancy outcome. The data from 355 patients
      who received standard in vitro fertilization (IVF) or intracytoplasmic sperm
      injection (ICSI) treatment after controlled ovarian hyperstimulation were
      recruited. Normal fertilized 3048 zygotes from 382 cycles were divided into two
      groups, PBs intact or fragmented, according to the morphology of PBs assessed at
      16-18 h after insemination. Embryo quality and pregnancy outcome were compared
      between the two groups. It was shown that the day 3 (D3) good embryo rate, good
      quality blastocyst rate and available embryo rate of the PBs intact group were
      all significantly higher than that of the corresponding fragmented groups.
      However, no significant differences in pregnancy rate (PR) or implantation rate
      (IR) were observed between the intact and fragmented groups. Although PBs
      morphology estimated at 16-18 h after insemination had little effect on PR or IR
      in fresh embryo transfer cycles, a better embryo quality can be achieved in the
      PB-intact group, which is valuable for embryo selection. 

PMID- 26198981
TI  - Corrigendum.

PMID- 26198983
TI  - Prohibitin protects proximal tubule epithelial cells against oxidative injury
      through mitochondrial pathways.
AB  - Oxidative stress mediated by reactive oxygen species (ROS) contributes to renal
      tubular atrophy and fibrosis following renal transplantation. Studies have shown
      that mitochondrial chaperone prohibitin (PHB) has antioxidant effects. Here we
      used the human renal proximal tubule epithelial cell line, HK-2 cells as an in
      vitro model to assess the role of PHB in hydrogen peroxide (H2O2)-induced renal
      tubular oxidative injury. Our results showed that H2O2 treatment inhibited PHB
      expression in a time-dependent manner in HK-2 cells. PHB overexpression could
      protect cell from oxidative stress-induced injury by inhibiting H2O2-induced cell
      apoptosis and intracellular ROS generation and promoting endogenous antioxidant
      defense components including glutathione peroxidase, catalase, superoxide
      dismutase, and glutathione. Furthermore, oxidative stress-induced cell injury was
      suppressed in PHB-overexpressed tubule epithelial cells through mitochondria
      mediated pathway, including inhibition of mitochondrial uncoupling protein 2 or
      UCP2 and Bax expression, mitochondrial ROS production, promotion of ATP
      production and Bcl-2 expression, inhibition of mitochondrial membrane potential
      loss and release of cytochrome c from mitochondria to cytoplasm, and followed by
      caspase-3 activation. Meanwhile, inhibition of PHB expression by small
      interference RNA resulted in less resistance of HK-2 cells to H2O2 toxicity as
      shown in decreased cell viability, increased apoptosis, ROS production, and
      mitochondrial dysfunction. These data indicated that PHB protected the tubule
      epithelial cells from oxidative stress-induced damage through the inhibition of
      oxidative damage, mitochondria dysfunction, and ultimately inhibition of cell
      apoptosis, and that increasing PHB content in mitochondria constituted a new
      therapeutic target for transient ischemic injury and chronic allograft
      nephropathy or CAN following renal transplantation. 

PMID- 26198984
TI  - Direct Spectroscopic Detection and EPR Investigation of a Ground State Triplet
      Phenyl Oxenium Ion.
AB  - Oxenium ions are important reactive intermediates in synthetic chemistry and
      enzymology, but little is known of the reactivity, lifetimes, spectroscopic
      signatures, and electronic configurations of these unstable species. Recent
      advances have allowed these short-lived ions to be directly detected in solution
      from laser flash photolysis of suitable photochemical precursors, but all of the
      studies to date have focused on aryloxenium ions having closed-shell singlet
      ground state configurations. To study alternative spin configurations, we
      synthesized a photoprecursor to the m-dimethylamino phenyloxenium ion, which is
      predicted by both density functional theory and MRMP2 computations to have a
      triplet ground state electronic configuration. A combination of femtosecond and
      nanosecond transient absorption spectroscopy, nanosecond time-resolved Resonance
      Raman spectroscopy (ns-TR(3)), cryogenic matrix EPR spectroscopy, computational
      analysis, and photoproduct studies allowed us to trace essentially the complete
      arc of the photophysics and photochemistry of this photoprecursor and permitted a
      first look at a triplet oxenium ion. Ultraviolet photoexcitation of this
      precursor populates higher singlet excited states, which after internal
      conversion to S1 over 800 fs are followed by bond heterolysis in ~1 ps,
      generating a hot closed-shell singlet oxenium ion that undergoes vibrational
      cooling in ~50 ps followed by intersystem crossing in ~300 ps to generate the
      triplet ground state oxenium ion. In contrast to the rapid trapping of singlet
      phenyloxenium ions by nucleophiles seen in prior studies, the triplet oxenium ion
      reacts via sequential H atom abstractions on the microsecond time domain to
      ultimately yield the reduced m-dimethylaminophenol as the only detectable stable
      photoproduct. Band assignments were made by comparisons to computed spectra of
      candidate intermediates and comparisons to related known species. The triplet
      oxenium ion was also detected in the ns-TR(3) experiments, permitting a more
      clear assignment and identifying the triplet state as the pi,pi* triplet
      configuration. The triplet ground state of this ion was further supported by
      photolysis of the photoprecursor in an ethanol glass at ~4 K and observing a
      triplet species by cryogenic EPR spectroscopy. 

PMID- 26198985
TI  - Loss of Host Type-I IFN Signaling Accelerates Metastasis and Impairs NK-cell
      Antitumor Function in Multiple Models of Breast Cancer.
AB  - Metastatic progression is the major cause of breast cancer-related mortality. By
      examining multiple syngeneic preclinical breast cancer models in mice lacking a
      functional type-I interferon receptor (Ifnar1(-/-) mice), we show that host
      derived type-I interferon (IFN) signaling is a critical determinant of metastatic
      spread that is independent of primary tumor growth. In particular, we show that
      bone metastasis can be accelerated in Balb/c Ifnar1(-/-) mice bearing either 4T1
      or 66cl4 orthotopic tumors and, for the first time, present data showing the
      development of bone metastasis in the C57Bl/6 spontaneous MMTV-PyMT-driven model
      of tumorigenesis. Further exploration of these results revealed that endogenous
      type-I IFN signaling to the host hematopoietic system is a key determinant of
      metastasis-free survival and critical to the responsiveness of the circulating
      natural killer (NK)-cell population. We find that in vivo-stimulated NK cells
      derived from wild-type, but not Ifnar1(-/-), mice can eliminate the 4T1 and 66cl4
      breast tumor lines with varying kinetics in vitro. Together, this study indicates
      that the dysregulated immunity resulting from a loss of host type-I IFN signaling
      is sufficient to drive metastasis, and provides a rationale for targeting the
      endogenous type-I IFN pathway as an antimetastatic strategy.

PMID- 26198987
TI  - Doctors and medical students in India should stop wearing white coats.

PMID- 26198986
TI  - Chemical profile and in vivo hypoglycemic effects of Syzygium jambos, Costus
      speciosus and Tapeinochilos ananassae plant extracts used as diabetes adjuvants
      in Puerto Rico.
AB  - BACKGROUND: The increasing numbers of people who use plant-based remedies as
      alternative or complementary medicine call for the validation of less known
      herbal formulations used to treat their ailments. Since Puerto Rico has the
      highest rate of Type 2 diabetes within all the states and territories of the
      United States, and Puerto Ricans commonly use plants as diabetes adjuvants, it is
      important to study the plants' physiological effects, and identify their
      bioactive compounds to understand their role in modulation of blood glucose
      levels. We present the phytochemical profiles and hypoglycemic effects of
      Tapeinochilus ananassae, Costus speciosus and Syzygium jambos. METHODS:
      Phytochemicals in methanolic and aqueous extracts were analyzed by thin layer
      chromatography (TLC). Alkaloids (Bromocresol green, lambda=470 nm), flavonoids
      (AlCl3, lambda=415 nm), saponins (DNS, lambda=760 nm), tannins (FeCl3/K4Fe(CN)6,
      lambda=395 nm) and phenolics (Folin-Ciocalteau, lambda=765 nm) were quantified.
      Male C57BLKS/J (db/db) and C57BL/J (ob/ob) genetically obese mice were orally
      gavaged with aqueous extracts of lyophilized plant decoctions for 10 wks.
      RESULTS: Our results show that T. ananassae had significantly greater amounts of
      flavonoids and tannins, while S. jambos showed the greatest concentration of
      phenolics and C. speciosus exhibited higher amounts of alkaloids. C57BLKS/J db/db
      treated with plant extracts show better glucose modulation when the extracts are
      administered in complement with an insulin injection. Finally, C57BL/J ob/ob mice
      on T. ananassae and S. jambos treatments show better blood glucose modulation
      over time. CONCLUSION: These results document for the first time the chemical
      profile of T. ananassae and provide evidence for a potential anti-diabetic
      efficacy of T. ananassae and S. jambos.

PMID- 26198989
TI  - A maintenance hemodialysis diabetic patient with unexplained pulmonary and
      gastrointestinal involvement.
AB  - A 50-year-old man with diabetes mellitus with diabetic retinopathy, peripheral
      neuropathy, hypertension, and end-stage renal disease on maintenance
      hemodialysis, presented with persistent cough and hiccups, continued to be unwell
      with weight loss, poor appetite, and recurrent respiratory symptoms such as
      wheezing and cough. Whole body positron emission tomography-computed tomography
      scan showed metabolically active lesions in liver, stomach/lesser sac, pancreas,
      and left sixth rib. As he had repeated bilateral transudative pleural effusion,
      left mini thoracotomy with pleural biopsy showed no evidence of granuloma or
      malignancy. Upper gastroscopy showed tiny gastric polyp; biopsy revealed benign
      lesion. Left posterior rib biopsy from the lesion and iliac crest biopsy showed
      no evidence of malignancy or granuloma. Further evaluation showed plasma
      chromogranin A -5737 MUg/L (<100 MUg/L) with a repeat value of 6950 MUg/L (<100
      MUg/L). He was initiated on oral sunitinib 25 mg once a day and injection
      octreotide 20 mg subcutaneously once a month. The plasma chromogranin A level and
      his symptoms, however, showed an initial improvement, but gradually worsened
      after 4 months despite being on treatment. After 6 months, the patient developed
      a gangrenous lesion of his glans penis with necrosis. Due to severe pain on
      conservative measures, penectomy with perineal urethrostomy was performed. Biopsy
      of the lesion showed blood vessels with intimal calcifications and thrombosis
      suggesting penile necrosis. 

PMID- 26198988
TI  - How women are treated during facility-based childbirth: development and
      validation of measurement tools in four countries - phase 1 formative research
      study protocol.
AB  - BACKGROUND: Every woman has the right to dignified, respectful care during
      childbirth. Recent evidence has demonstrated that globally many women experience
      mistreatment during labour and childbirth in health facilities, which can pose a
      significant barrier to women attending facilities for delivery and can contribute
      to poor birth experiences and adverse outcomes for women and newborns. However
      there is no clear consensus on how mistreatment of women during childbirth in
      facilities is defined and measured. We propose using a two-phased, mixed-methods
      study design in four countries to address these research gaps. This protocol
      describes the Phase 1 qualitative research activities. METHODS/DESIGN: We will
      employ qualitative research methodologies among women, healthcare providers and
      administrators in the facility catchment areas of two health facilities in each
      country: Ghana, Guinea, Myanmar and Nigeria. In-depth interviews (IDIs) and focus
      group discussions (FGDs) will be conducted among women of reproductive age (15-49
      years) to explore their perceptions and experiences of facility-based childbirth
      care, focused on how they were treated by healthcare workers and perceived
      factors affecting how they were treated. IDIs will also be conducted with
      healthcare providers of different cadres (e.g.: nurses, midwives, medical
      officers, specialist obstetricians) and facility administrators working in the
      selected facilities to explore healthcare providers' perceptions and experiences
      of facility-based childbirth care and how staff are treated, colleagues and
      supervisors. Audio recordings will be transcribed and translated to English.
      Textual data will be analysed using a thematic framework approach and will
      consist of two levels of analysis: (1) conduct of local analysis workshops with
      the research assistants in each country; and (2) line-by-line coding to develop a
      thematic framework and coding scheme. DISCUSSION: This study serves several
      roles. It will provide an in-depth understanding of how women are treated during
      childbirth in four countries and perceived factors associated with this
      mistreatment. It will also provide data on where and how an intervention could be
      developed to reduce mistreatment and promote respectful care. The findings from
      this study will contribute to the development of tools to measure the prevalence
      of mistreatment of women during facility-based childbirth.

PMID- 26198990
TI  - Implementation of iodine biokinetic model for interpreting I-131 contamination in
      breast milk after the Fukushima nuclear disaster.
AB  - After the accident at the Fukushima Daiichi Nuclear Power Plant run by Tokyo
      Electric Power Company in 2011, breast milk samples obtained from volunteers
      living in Fukushima and neighboring prefectures were examined and small amounts
      of I-131 (2.2-36.3 Bq/kg) were detected in some samples. In this work, the I-131
      concentrations in breast milk from nursing mothers in Ibaraki prefecture were
      calculated based on the iodine biokinetic model during lactation together with
      time-variable intake scenarios by inhalation of ambient air and ingestion of tap
      water, using the authors' code. The calculated I-131 concentrations in breast
      milk generally agreed with those measured for the volunteers. Based on the
      results, thyroid equivalent doses to breast-fed infants were estimated for each
      place of residence of the volunteers on the assumption that these infants
      consumed 800 ml of breast milk every day, resulting in 10-11 mSv for Mito and
      Kasama cities and 1.1-1.8 mSv for Tsukuba and Moriya cities. It was suggested
      that breast milk consumption could be a major contributor to internal dose of
      breast-fed infants in areas with mild I-131 pollution; however, further studies
      considering personal behavior surveys would be necessary to estimate individual
      doses. 

PMID- 26198991
TI  - Single nucleotide polymorphisms associated with thermoregulation in lactating
      dairy cows exposed to heat stress.
AB  - Dairy cows with increased rectal temperature experience lower milk yield and
      fertility. Rectal temperature during heat stress is heritable, so genetic
      selection for body temperature regulation could reduce effects of heat stress on
      production. One aim of the study was to validate the relationship between
      genotype and heat tolerance for single nucleotide polymorphisms (SNPs) previously
      associated with resistance to heat stress. A second aim was to identify new SNPs
      associated with heat stress resistance. Thermotolerance was assessed in lactating
      Holsteins during the summer by measuring rectal temperature (a direct measurement
      of body temperature regulation; n = 435), respiration rate (an indirect
      measurement of body temperature regulation, n = 450) and sweating rate (the major
      evaporative cooling mechanism in cattle, n = 455). The association between
      genotype and thermotolerance was evaluated for 19 SNPs previously associated with
      rectal temperature from a genomewide analysis study (GWAS), four SNPs previously
      associated with change in milk yield during heat stress from GWAS, 2 candidate
      gene SNPs previously associated with rectal temperature and respiration rate
      during heat stress (ATPA1A and HSP70A) and 66 SNPs in genes previously shown to
      be associated with reproduction, production or health traits in Holsteins. For
      SNPs previously associated with heat tolerance, regions of BTA4, BTA6 and BTA24
      were associated with rectal temperature; regions of BTA6 and BTA24 were
      associated with respiration rate; and regions of BTA5, BTA26 and BTA29 were
      associated with sweating rate. New SNPs were identified for rectal temperature (n
      = 12), respiration rate (n = 8) and sweating rate (n = 3) from among those
      previously associated with production, reproduction or health traits. The SNP
      that explained the most variation were PGR and ASL for rectal temperature, ACAT2
      and HSD17B7 for respiration rate, and ARL6IP1 and SERPINE2 for sweating rate.
      ARL6IP1 was associated with all three thermotolerance traits. In conclusion,
      specific genetic markers responsible for genetic variation in thermoregulation
      during heat stress in Holsteins were identified. These markers may prove useful
      in genetic selection for heat tolerance in Holstein cattle.

PMID- 26198992
TI  - Development and validation of the Female Sexual Function Index adaptation for
      breast cancer patients (FSFI-BC).
AB  - Sexual dysfunction following breast cancer treatment is common and screening for
      this is recommended. This study determined the reliability, validity, and
      acceptability of a breast cancer-specific adaptation of the Female Sexual
      Function Index, the FSFI-BC. This new measure addresses limitations in the FSFI
      when assessing sexual dysfunction of women with breast cancer regarding
      applicability to non-sexually active women, measuring distress and changes after
      cancer. Female breast cancer survivors (n = 596; 429 sexually active, 166 non
      sexually active) completed an online survey including demographic/medical
      information, the FSFI-BC, and scales measuring sexual functioning, fatigue, body
      image, physical and mental health, and relationship adjustment (Time 1). Three
      weeks later, 326 women (245 sexually active; 81 non-sexually active) completed
      the Time 2 survey including the FSFI-BC, and questions regarding its
      acceptability and perceived change in sexual functioning. Reliability, construct
      validity, and acceptability were examined using standard scale validation
      techniques. Exploratory factor analysis delineated seven factors: Changes after
      cancer, desire/arousal, lubrication, orgasm, pain, satisfaction, and distress,
      accounting for 79.98 % (sexually active) and 77.19 % (non-active) variance in
      responses. Acceptable internal consistencies (non-active: alpha = 0.71-0.96;
      sexually active: alpha = 0.89-0.96) and test-retest reliabilities (non-active: r
      = 0.63-0.86; sexually active: r = 0.71-0.88) were evident. Inter-scale
      correlations provided evidence for convergent and divergent validities of the
      FSFI-BC. Both sexually active and non-active women provided positive feedback
      about the FSFI-BC. The optional partner questions demonstrated clinical utility.
      With desirable psychometric properties and acceptability to participants, the
      FSFI-BC is suitable for screening for sexual dysfunction in women with breast
      cancer.

PMID- 26198993
TI  - Quantitative changes in skin composition parameters due to chemotherapy in breast
      cancer patients: a cohort study.
AB  - The objective of this study is to evaluate objective changes in water content,
      sebum content, transepidermal water loss (TEWL), and melanin due to breast cancer
      chemotherapy, and their association with subjective symptoms. Prospective cohort
      study of 61 patients 18 years of age or older with a postoperative diagnosis of
      stage I-III breast cancer, who received adjuvant chemotherapy between February
      and September 2012 at an outpatient breast cancer clinic in Korea. Objective skin
      parameters, measured using a noninvasive bioengineering device, and patient
      reported dryness and dullness were assessed before chemotherapy, after two cycles
      of chemotherapy, and 1, 3, and 6 months after completion of chemotherapy. Water
      content (-6.5 %), sebum (-75.5 %), and TEWL (-22.4 %) significantly decreased
      during chemotherapy compared to pre-chemotherapy levels (all p values <0.001).
      These parameters were lowest at 1 month after completion of chemotherapy and
      recovered thereafter but did not return to baseline levels after 6 months of
      follow-up. Melanin increased during chemotherapy with respect to pre-chemotherapy
      levels (8.4 %; p < 0.001) but decreased from the first month after completion of
      chemotherapy through the end of follow-up (-17.1 %; p < 0.001). The patterns of
      skin changes were similar in patients with or without hormone therapy. Most of
      patients reported dryness (57.9 %) and dullness (49.1 %) after chemotherapy, and
      patient-reported dryness was significantly associated with decreased sebum
      content. Chemotherapy-induced substantial changes in objective skin composition
      parameters. These changes persisted after 6 months from completion of
      chemotherapy and were associated with patient-reported symptoms. Additional
      research is needed to translate these findings into interventions for improving
      the dermatologic quality of life of breast cancer patients undergoing
      chemotherapy.

PMID- 26198995
TI  - A rare cause of constipation: obstructing small cell neuroendocrine carcinoma of
      the anal canal.

PMID- 26198994
TI  - Chronic radiation proctitis: tricks to prevent and treat.
AB  - OBJECTIVE: The purpose of this study was to give an overview of the measures used
      to prevent chronic radiation proctitis (CRP) and to provide an algorithm for the
      treatment of CRP. METHODS: Medical literature databases including PubMed and
      Medline were screened and critically analyzed for relevance in the scope of our
      purpose. RESULTS: CRP is a relatively frequent late side effect (5-20%) and
      mainly dependent on the dose and volume of irradiated rectum. Radiation treatment
      (RT) techniques to prevent CRP are constantly improving thanks to image-guided RT
      and intensity-modulated RT. Also, newer techniques like protons and new devices
      such as rectum spacers and balloons have been developed to spare rectal
      structures. Biopsies do not contribute to diagnosing CRP and should be avoided
      because of the risk of severe rectal wall damage, such as necrosis and fistulas.
      There is no consensus on the optimal treatment of CRP. A variety of possibilities
      is available and includes topical and oral agents, hyperbaric oxygen therapy, and
      endoscopic interventions. CONCLUSIONS: CRP has a natural history of improving
      over time, even without treatment. This is important to take into account when
      considering these treatments: first be conservative (topical and oral agents) and
      be aware that invasive treatments can be very toxic.

PMID- 26198996
TI  - Postoperative hyperglycemia and adverse outcomes in patients undergoing
      colorectal surgery: results from the Michigan surgical quality collaborative
      database.
AB  - PURPOSE: Our objective was to assess the relationship between high blood glucose
      levels (BG) in the early postoperative period and the incidence of surgical site
      infections (SSIs), sepsis, and death following colorectal operations. METHODS:
      The Michigan Surgical Quality Collaborative database was queried for colorectal
      operations from July 2012 to December 2013. Normoglycemic (BG < 180 mg/dL) and
      hyperglycemic (BG >= 180 mg/dL) groups were defined by using the highest BG
      within the first 72 h postoperatively. Outcomes of interest included the
      incidence of superficial, deep, and organ/space SSIs, sepsis, and death within 30
      days. Initial unadjusted analysis was followed by propensity score matching and
      multiple logistic regression modeling after adjusting for significant predictors.
      Separate analyses were performed for previously diagnosed diabetic and non
      diabetic patients. RESULTS: A total of 5145 cases met inclusion criteria, of
      which 1072 were diabetic. For diabetic patients, there was a marginally
      significant association between high BG and superficial SSI in the unadjusted
      analysis (OR = 1.75, p = 0.056), but not in the adjusted analysis (OR = 1.35, p =
      0.39). There was no significant relationship between elevated BG and deep SSI,
      organ/space SSI, sepsis, or death among diabetic patients. For non-diabetic
      patients, there was a significant association between high BG and superficial SSI
      (OR = 1.53, p = 0.03), sepsis (OR = 1.61, p < 0.01), and death (OR = 2.26, p <
      0.01), but not deep or organ/space SSI. CONCLUSIONS: Following colorectal
      operations, superficial SSI, sepsis, and death are associated with postoperative
      serum hyperglycemia in patients without diabetes, but not those with diabetes.
      Vigilant postoperative BG monitoring is critical for all patients undergoing
      colorectal surgery.

PMID- 26198997
TI  - Negative surgical margin improved long-term survival of colorectal cancer liver
      metastases after hepatic resection: a systematic review and meta-analysis.
AB  - OBJECTIVE: The need to achieve a tumor-free margin of >=1 mm (R0) for colorectal
      liver metastases (CRLM) after hepatic resection has been questioned recently.
      This study conducted a meta-analysis to determine whether status of the surgical
      margin still influenced the long-term outcome of survival and recurrence rate.
      METHODS: Eligible trials that compared survival and recurrence rates of R0 versus
      the tumor-free margin <1 mm (R1) were identified from Embase, PubMed, the Web of
      Science, and the Cochrane Library since their inception to 1 March 2015. The
      study outcomes included long-term outcome of survival and recurrence rate. Hazard
      ratio (HR) with a 95 % confidence interval was used to measure the pooled effect
      according to a random-effects model or fixed-effects model, depending on the
      heterogeneity among the included studies. The heterogeneity among these trials
      was statistically evaluated using the chi(2) and I(2) tests. Sensitivity analyses
      and publication bias were also carried out. RESULTS: A total of 18 studies
      containing 6790 patients were included. The comparison between R1 and R0 revealed
      that a pooled HR for 5-year overall survival was 1.603 (95 % CI; 1.464-1.755; p =
      0.000; I(2) = 31.2 %, p = 0.141). For patients received modern chemotherapy; a
      pooled HR of R1 resection for 5-year overall survival was 1.924 (95 % CI; 1.567
      2.361, p = 0.000; I(2) = 20.5 %, p = 0.273). The pooled HR for 5-year OS of >=1
      cm in the included studies calculated using the random-effects model was 0.819
      (95 % CI; 0.715-0.938, p = 0.004; I(2) = 0 %, p = 0.492). CONCLUSIONS: R1
      resections decreased long-term survival, and modern chemotherapy did not alter an
      adverse outcome. Surgeons should attempt to obtain a 1-cm margin.

PMID- 26198998
TI  - Multiple coupling in plasmonic metal/dielectric hollow nanocavity arrays for
      highly sensitive detection.
AB  - Recently, the plasmonic coupled optical cavity has gained much attention due to
      its attractive properties in light manipulation, e.g. high Q optical resonance,
      local field enhancements and extraordinary transmission. The strongly enhanced
      local field originated from the plasmonic resonance hybridizing with the optical
      cavity mode presents great potential for application to chemical and biological
      sensing. Here, the multiple coupling effect between plasmonic mode and optical
      cavity mode has been demonstrated in self-assembled metal/dielectric hollow
      nanosphere (HNS) arrays and the strongly enhanced local field originated from the
      inter-coupling of the plasmonic cavities was further employed for highly
      sensitive recyclable SERS sensing. 

PMID- 26198999
TI  - Dietary therapy is the best option for refractory nonsurgical epilepsy.
AB  - Ketogenic diet therapies for epilepsy have been described since the fifth century
      and published in scientific literature since the early 1900s. Since that time,
      the diet's popularity has waxed and waned as newer drugs and other treatments
      have been introduced. However, in recent years, dietary therapy for epilepsy has
      been increasingly accepted by physicians and desired by patients as an
      alternative to new drugs and neurostimulation. The introduction of less
      restrictive versions of the classic ketogenic diet, such as the modified Atkins
      diet (MAD), have led to increased numbers of adult patients with refractory
      epilepsy who are initiating dietary treatment. Approximately half of adults and
      children who start a ketogenic diet have a >50% seizure reduction, which is
      impressive given that these patients typically have medically refractory
      epilepsy. We believe that ketogenic dietary treatment is the best option for
      children and adults with refractory nonsurgical epilepsy due to its efficacy,
      rapid seizure reduction, synergistic effects with other antiseizure treatments,
      known and treatable side effects, potential to treat comorbid medical conditions,
      and worldwide availability. 

PMID- 26199000
TI  - 13-year nationwide cohort study of chronic kidney disease risk among treatment
      naive patients with chronic hepatitis B in Taiwan.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection and chronic kidney disease
      (CKD) have high prevalences in Taiwan and worldwide. However, the association of
      untreated chronic hepatitis B virus (HBV) infection with chronic kidney disease
      (CKD) remains unclear. METHODS: This cohort study used claims data in the Taiwan
      National Health Insurance Research Database in 1996-2010, in which all diseases
      were classified by ICD-9-CM codes. We identified 17796 adults who had chronic HBV
      infection and did not take nucleos(t)ide analogues from 1998 to 2010 and also
      randomly selected 71184 matched controls without HBV in the same dataset.
      Cumulative incidences and adjusted hazard ratio (aHR) of incident CKD were
      evaluated through the end of 2010 after adjusting for competing mortality.
      RESULTS: The risk of CKD was significantly higher in the HBV cohort (13-year
      cumulative incidence, 6.2 %; 95 % confidence interval [CI], 5.4-7.1 %) than in
      the non-HBV cohort (2.7 %; 95 % CI, 2.5-3.0 %) (p < 0.001), and the aHR was 2.58
      (95 % CI, 1.95-3.42; p < 0.001). Multivariable stratified analysis further
      verified significant associations of CKD with HBV in men of any age (aHR, 2.98;
      95 % CI, 2.32-3.83, p < 0.001 for men aged <50 years; aHR, 1.58; 95 % CI, 1.31
      1.91, p < 0.001 for men aged ? 50 years) and women under the age of 50 (aHR,
      2.99; 95 % CI, 2.04-4.42, p < 0.001), but no significant association in women
      aged 50 or over. CONCLUSION: Untreated chronic HBV infection is associated with
      increased risk of CKD. Hence, high-risk HBV-infected subjects should have
      targeted monitoring for the development of CKD.

PMID- 26199001
TI  - Biliary tract external drainage increases the expression levels of heme oxygenase
      1 in rat livers.
AB  - BACKGROUND: Heme oxygenase-1 (HO-1) protects cells by anti-oxidation, maintaining
      normal microcirculation and anti-inflammatory under stress. This study
      investigated the effects of biliary tract external drainage (BTED) on the
      expression levels of HO-1 in rat livers. METHODS: Biliary tract external drainage
      was performed by inserting a cannula into the bile duct. Sixty Sprague-Dawley
      rats were randomized to the following groups: sham 1 h group; BTED 1 h group;
      bile duct ligation (BDL) 1 h group; sham 6 h group and BTED 6 h group. The
      expression levels of HO-1 mRNA were analyzed using real-time RT-PCR. The
      expression levels of HO-1 were analyzed using immunohistochemistry. RESULTS: The
      expression levels of HO-1 mRNA in the liver of the BTED group increased
      significantly compared with the sham group 1 and 6 h after surgery (p < 0.05).The
      expression levels of HO-1 in the BTED group increased significantly compared with
      the sham group 1 and 6 h after surgery. The expression levels of HO-1 mRNA in the
      liver in the BDL group decreased significantly compared with the sham group 1 h
      after surgery (p < 0.05).The expression levels of HO-1 in the BDL group decreased
      significantly compared with the sham group at this time. CONCLUSION: Biliary
      tract external drainages increase the expression levels of HO-1 in the liver.

PMID- 26199002
TI  - Assimilation of remote sensing observations into a sediment transport model of
      China's largest freshwater lake: spatial and temporal effects.
AB  - Numerical models are important tools that are used in studies of sediment
      dynamics in inland and coastal waters, and these models can now benefit from the
      use of integrated remote sensing observations. This study explores a scheme for
      assimilating remotely sensed suspended sediment (from charge-coupled device (CCD)
      images obtained from the Huanjing (HJ) satellite) into a two-dimensional sediment
      transport model of Poyang Lake, the largest freshwater lake in China. Optimal
      interpolation is used as the assimilation method, and model predictions are
      obtained by combining four remote sensing images. The parameters for optimal
      interpolation are determined through a series of assimilation experiments
      evaluating the sediment predictions based on field measurements. The model with
      assimilation of remotely sensed sediment reduces the root-mean-square error of
      the predicted sediment concentrations by 39.4% relative to the model without
      assimilation, demonstrating the effectiveness of the assimilation scheme. The
      spatial effect of assimilation is explored by comparing model predictions with
      remotely sensed sediment, revealing that the model with assimilation generates
      reasonable spatial distribution patterns of suspended sediment. The temporal
      effect of assimilation on the model's predictive capabilities varies spatially,
      with an average temporal effect of approximately 10.8 days. The current
      velocities which dominate the rate and direction of sediment transport most
      likely result in spatial differences in the temporal effect of assimilation on
      model predictions.

PMID- 26199003
TI  - Dynamic water quality modelling and uncertainty analysis of phytoplankton and
      nutrient cycles for the upper South Saskatchewan River.
AB  - The surface water quality of the upper South Saskatchewan River was modelled
      using Water Quality Analysis Simulation Program (WASP) 7.52. Model calibration
      and validation were based on samples taken from four long-term water quality
      stations during the period 2007-2009. Parametric sensitivities in winter and
      summer were examined using root mean square error (RMSE) and relative entropy.
      The calibration and validation results show good agreement between model
      prediction and observed data. The two sensitivity methods confirmed pronounced
      parametric sensitivity to model state variables in summer compared to winter. Of
      the 24 parameters examined, dissolved oxygen (DO) and ammonia (NH3-N) are the
      most influenced variables in summer. Instream kinetic processes including
      nitrification, nutrient uptake by algae and algae respiration induce a higher
      sensitivity on DO in summer than in winter. Moreover, in summer, soluble reactive
      phosphorus (SRP) and chlorophyll-a (Chla) variables are more sensitive to algal
      processes (nutrient uptake and algae death). In winter however, there exists some
      degree of sensitivity of algal processes (algae respiration and nutrient uptake)
      to DO and NH3-N. Results of this study provide information on the state of the
      river water quality which impacts Lake Diefenbaker and the need for additional
      continuous monitoring in the river. The results of the sensitivity analysis also
      provide guidance on most sensitive parameters and kinetic processes that affect
      eutrophication for preliminary surface water quality modelling studies in cold
      regions. 

PMID- 26199004
TI  - Removal of trihalomethane from chlorinated seawater using gamma radiation.
AB  - Chlorine addition as a biocide in seawater results in the formation of
      chlorination by-products such as trihalomethanes (THMs). Removal of THMs is of
      importance as they are potential mutagenic and carcinogenic agents. In this
      context, a study was conducted that used ionizing radiation to remove THMs from
      chlorinated (1, 3, and 5 mg/L) seawater by applying various dosages (0.4-5.0 kGy)
      of gamma radiation. Bromoform (BF) showed a faster rate of degradation as
      compared to other halocarbons such as bromodichloromethane (BDCM) and
      dibromochloromethane (DBCM). In chlorine-dosed seawater, total irradiation dose
      of 0.4 to 5 kGy caused percentage reduction in the range of 6.9 to 76.7%, 2.3 to
      99.6%, and 45.7 to 98.3% for BDCM, DBCM, and BF, respectively. During the
      irradiation process, pH of the chlorinated seawater decreased with increase in
      the absorbed dose; however, no change in total organic carbon (TOC) was observed.
      The results show that gamma dose of 2.5 kGy was adequate for maximum degradation
      of THM; but for complete mineralization, higher dose would be required.

PMID- 26199005
TI  - Occurrence of 1153 organic micropollutants in the aquatic environment of Vietnam.
AB  - The rapid increase in the number and volume of chemical substances being used in
      modern society has been accompanied by a large number of potentially hazardous
      chemicals being found in environmental samples. In Vietnam, the monitoring of
      chemical substances is mainly limited to a small number of known pollutants in
      spite of rapid economic growth and urbanization, and there is an urgent need to
      examine a large number of chemicals to prevent impacts from expanding
      environmental pollution. However, it is difficult to analyze a large number of
      chemicals using existing methods, because they are time consuming and expensive.
      In the present study, we determined 1153 substances to grasp a pollution picture
      of microcontaminants in the aquatic environment. To achieve this objective, we
      have used two comprehensive analytical methods: (1) solid-phase extraction (SPE)
      and LC-TOF-MS analysis, and (2) SPE and GC-MS analysis. We collected 42 samples
      from northern (the Red River and Hanoi), central (Hue and Danang), and southern
      (Ho Chi Minh City and Saigon-Dongnai River) Vietnam. One hundred and sixty-five
      compounds were detected at least once. The compounds detected most frequently
      (>40 % samples) at MUg/L concentrations were sterols (cholesterol, beta
      sitosterol, stigmasterol, coprostanol), phthalates (bis(2-ethylhexyl) phthalate
      and di-n-butyl phthalate), and pharmaceutical and personal care products
      (caffeine, metformin). These contaminants were detected at almost the same
      detection frequency as in developed countries. The results reveal that surface
      waters in Vietnam, particularly in the center of large cities, are polluted by a
      large number of organic micropollutants, with households and business activities
      as the major sources. In addition, risk quotients (MEC/PNEC values) for
      nonylphenol, sulfamethoxazole, ampicillin, acetaminophen, erythromycin and
      clarithromycin were higher than 1, which indicates a possibility of adverse
      effects on aquatic ecosystems.

PMID- 26199006
TI  - Effects of surrounding land use on metal accumulation in environments and
      submerged plants in subtropical ponds.
AB  - Ponds are widely used as stormwater treatment facilities to retain contaminants,
      including metals, and to improve water quality throughout the world. However,
      there is still a limited understanding of the effects of surrounding land use on
      metal accumulation in pond environments and organisms. To address this gap, we
      measured the concentrations of nine metals (i.e., Al, Ba, Ca, K, Li, Mg, Na, Se,
      and Sr) in water, sediments, and submerged plants collected from 37 ponds with
      different surrounding land uses in southwestern China and assessed the metal
      accumulation capacity of four dominant submerged plant species. Our results
      showed that Al, Ca, and K concentrations in the water were above drinking water
      standards. In the sediments, the average concentrations of Ca and Sr were higher
      than the corresponding soil background values. Ceratophyllum demersum L. could
      accumulate more K in aboveground biomass than Myriophyllum spicatum L. and
      Potamogeton maackianus A. Benn. The K concentration in submerged plants was
      positively influenced by the corresponding metal concentration in the water and
      negatively influenced by water temperature. Among the nine studied metals, only
      the water K concentration in ponds receiving agricultural runoff was
      significantly higher than that for ponds receiving urban and forested runoff.
      This result suggests that surrounding land use types have no significant effect
      on metal accumulation in sediments and submerged plants in the studied ponds. A
      large percentage of the metals in these ponds may be derived from natural sources
      such as the weathering of rocks. 

PMID- 26199007
TI  - Effect of nitrate and ammonium fertilization on Zn, Pb, and Cd phytostabilization
      by Populus euramericana Dorskamp in contaminated technosol.
AB  - This study aimed at assessing the effect of nitrogen addition under two forms,
      nitrate and ammonium, on the stabilization of Zn, Pb, and Cd by Populus
      euramericana Dorskamp grown in contaminated soils for 35 days under controlled
      conditions. Temporal changes in the soil pore water (SPW) were monitored for pH,
      dissolved organic carbon (DOC), and total dissolved concentrations of metals in
      the soils rhizosphere. Rhizospheric SPW pH decreased gradually with NH4(+)
      addition and increased with NO3(-) addition up to one unit, while it slightly
      decreased initially then increased for the untreated control soil DOC increased
      with time up to six times, the highest increase occurring with NH4(+)
      fertilization. An increase in the metal concentrations in the rhizospheric SPW
      was observed for NH4(+) addition associated with the lowest rhizospheric SPW pH,
      whereas the opposite was observed for the control soil and NO3(-) fertilization.
      Fertilization did not affect plant shoots or roots biomass development compared
      to the untreated control (without N addition). Metals were mostly accumulated in
      the rhizosphere and N fertilization increased the accumulation for Zn and Pb
      while Cd accumulation was enhanced for NH4(+) addition. Collectively, our results
      suggest metal stabilization by P. euramericana Dorskamp rhizosphere with nitrogen
      fertilization and are potential for phytostabilization of contaminated technosol.

PMID- 26199008
TI  - Dicamba and 2,4-D residues following applicator cleanout: A potential point
      source to the environment and worker exposure.
AB  - This paper presents a survey of pesticide residues in tanks following application
      and throughout the cleanout procedure as conducted by 46 volunteer operators
      across Colorado. While many pesticides were detected, this paper focuses on
      dicamba and 2,4-D, which were detected by liquid chromatography/tandem mass
      spectroscopy (LC-MS/MS). An exponential decrease in concentration was observed
      with sequential rinses, although this decrease may be more rapid for more water
      soluble pesticides. More than 95% of the pesticide in the prerinse solution was
      removed by the end of the third rinse in all but three operator samples.
      Concentrations after three rinses were 0.41 +/- 0.25 and 3.3 +/- 1.1 mg/L for
      dicamba and 2,4-D, respectively. These concentrations suggest that the
      recommended practice of three rinses may not be adequate to eliminate off-target
      effects or point sources of pesticide waste, and that the recommended standard of
      personal protective equipment is essential to prevent worker exposure to the
      chemicals. IMPLICATIONS: This paper demonstrates that the waste generated during
      cleanout of pesticide application devices constitutes a potential source of
      pollution and worker exposure. In particular, while the first rinse of pesticide
      containers is often treated as hazardous waste and reapplied to crops, the
      remaining rinses are not. This work demonstrates that the wastewater generated in
      subsequent rinses can have high enough concentrations to impact worker health,
      cause off-target effects on crops, and potentially constitute a point source of
      pesticides. The practical implication is for improved recommendations and
      regulations regarding pesticide applicators and their cleanout process.

PMID- 26199009
TI  - Impact of parathyroidectomy on survival among haemodialysis patients: A
      prospective cohort study.
AB  - AIM: We evaluated whether parathyroidectomy (PTX) was associated with survival of
      dialysis patients. METHODS: In a cohort study with one year follow-up, data from
      146 haemodialysis patients from a hospital were analyzed. We compared the
      baseline data between patients receiving PTX surgery and those who had not
      undergone PTX. The Cox proportional hazards regression was used to examine the
      effect of PTX. RESULTS: Patients who had received PTX surgery were more likely to
      be older, have longer duration of dialysis, higher ultrafiltration rate, C
      reactive protein (CRP), alkaline phosphatase (ALP), and lower albumin compared
      with those who had not receive PTX. During 1 year follow-up, 21 (17.1%) patients
      died, of whom seven died from cerebrovascular events, 10 died from cardiovascular
      disease, and four died from infection. The mortality was 9.4% in the PTX group
      and 17.3% in the control group. The PTX group had a significantly lower risk of
      all-cause mortality than the control group (P = 0.005). There was a significantly
      lower risk of all-cause mortality in the PTX group compared with the non-PTX
      group (HR = 0.93, 95%CI: 0.89-0.97). The lower risk (HR = 0.92, 95%CI: 0.85-0.98)
      of PTX group was not changed after adjusting potential factors. Our results also
      suggested that this relationship was independent of many potential confounding
      factors. CONCLUSION: Parathyroidectomy was related to significant reduction in
      all-cause among patients with severe SHPT. PTX may be considered as a matter of
      priority, from which dialysis patients would benefit.

PMID- 26199011
TI  - A novel polymer containing phosphorus-nitrogen ligands for stabilization of
      palladium nanoparticles: an efficient and recyclable catalyst for Suzuki and
      Sonogashira reactions in neat water.
AB  - A new polymer containing phosphorus and nitrogen ligands was successfully
      synthesized, characterized and used for the stabilization of highly monodispersed
      palladium nanoparticles having an average diameter of 2-3 nm. The thermally
      stable heterogeneous catalyst was successfully applied in Suzuki-Miyaura and
      copper-free Sonogashira-Hagihara coupling reactions of aryl halides under low
      palladium loading conditions. Reactions were proceeded in neat water without
      using any organic co-solvents. The catalyst was successfully recycled for the
      sample Suzuki-Miyaura reaction nine consecutive times with small drop in
      catalytic activity. 

PMID- 26199010
TI  - The serine/threonine kinase 33 is present and expressed in palaeognath birds but
      has become a unitary pseudogene in neognaths about 100 million years ago.
AB  - BACKGROUND: Serine/threonine kinase 33 (STK33) has been shown to be conserved
      across all major vertebrate classes including reptiles, mammals, amphibians and
      fish, suggesting its importance within vertebrates. It has been shown to
      phosphorylate vimentin and might play a role in spermatogenesis and organ
      ontogenesis. In this study we analyzed the genomic locus and expression of stk33
      in the class Aves, using a combination of large scale next generation sequencing
      data analysis and traditional PCR. RESULTS: Within the subclass Palaeognathae we
      analyzed the white-throated tinamou (Tinamus guttatus), the African ostrich
      (Struthio camelus) and the emu (Dromaius novaehollandiae). For the African
      ostrich we were able to generate a 62,778 bp long genomic contig and an mRNA
      sequence that encodes a protein showing highly significant similarity to STK33
      proteins from other vertebrates. The emu has been shown to encode and transcribe
      a functional STK33 as well. For the white-throated tinamou we were able to
      identify 13 exons by sequence comparison encoding a protein similar to STK33 as
      well. In contrast, in all 28 neognath birds analyzed, we could not find evidence
      for the existence of a functional copy of stk33 or its expression. In the genomes
      of these 28 bird species, we found only remnants of the stk33 locus carrying
      several large genomic deletions, leading to the loss of multiple exons. The
      remaining exons have acquired various indels and premature stop codons.
      CONCLUSIONS: We were able to elucidate and describe the genomic structure and the
      transcription of a functional stk33 gene within the subclass Palaeognathae, but
      we could only find degenerate remnants of stk33 in all neognath birds analyzed.
      This led us to the conclusion that stk33 became a unitary pseudogene in the
      evolutionary history of the class Aves at the paleognath-neognath branch point
      during the late cretaceous period about 100 million years ago. We hypothesize
      that the pseudogenization of stk33 might have become fixed in neognaths due to
      either genetic redundancy or a non-orthologous gene displacement and present
      potential candidate genes for such an incident.

PMID- 26199012
TI  - Purification, characterization and synergism in autolysis of a group of 1,3-beta
      glucan hydrolases from the pilei of Coprinopsis cinerea fruiting bodies.
AB  - Using a combined chromatography method, we simultaneously purified three protein
      fractions (II-2, II-3 and II-4) with 1,3-beta-glucanase activity from extraction
      of pilei of Coprinopsis cinerea fruiting bodies. MALDI-TOF/TOF amino acid
      sequencing showed that these three fractions matched a putative exo-1,3-beta
      glucanase, a putative glucan 1,3-beta-glucosidase and a putative glycosyl
      hydrolase family 16 protein annotated in the C. cinerea genome, respectively;
      however, they were characterized as a 1,3-beta-glucosidase, an exo-1,3-beta
      glucanase and an endo-1,3-beta-glucanase, respectively, by analysis of their
      substrate specificities and modes of action. This study explored how these three
      1,3-beta-glucoside hydrolases synergistically acted on laminarin: the endo-1,3
      beta-glucanase hydrolysed internal glycosidic bonds of laminarin to generate 1,3
      beta-oligosaccharides of various lengths, the exo-1,3-beta-glucanase cleaved the
      longer-chain laminarioligosaccharides into short-chain disaccharides,
      laminaribiose and gentiobiose, and the 1,3-beta-glucosidase further hydrolysed
      laminaribiose to glucose. The remaining gentiobiose must be hydrolysed by other
      1,6-beta-glucosidases. Therefore, the endo-1,3-beta-glucanase, exo-1,3-beta
      glucanase and 1,3-beta-glucosidase may act synergistically to completely degrade
      the 1,3-beta-glucan backbone of the C. cinerea cell wall during fruiting body
      autolysis. These three 1,3-beta-glucoside hydrolases share a similar optimum pH
      and optimum temperature, supporting the speculation that these enzymes work
      together under the same conditions to degrade 1,3-beta-glucan in the C. cinerea
      cell wall during fruiting body autolysis.

PMID- 26199013
TI  - Association between suicidal behaviour and impaired glucose metabolism in
      depressive disorders.
AB  - BACKGROUND: Disturbances in lipid metabolism have been linked to suicidal
      behaviour, but little is known about the association between suicide risk and
      abnormal glucose metabolism in depression. Hyperglycaemia and hyperinsulinaemia
      may increase the risk of depression and also the risk for suicide, we therefore
      studied associations between suicidal behaviour and disturbances in glucose
      metabolism in depressive patients who had been referred to depression nurse case
      managers. METHODS: Patients aged 35 years and older (N = 448, mean age 51 years)
      who were experiencing a new depressive episode, who were referred to depression
      nurse case managers in 2008-2009 and who scored >=10 on the Beck Depression
      Inventory were enrolled in this study. The study was conducted in municipalities
      within the Central Finland Hospital District (catchment area of 274 000
      inhabitants) as part of the Finnish Depression and Metabolic Syndrome in Adults
      study. The patients' psychiatric diagnoses and suicidal behaviour were confirmed
      by the Mini-International Neuropsychiatric Interview. Blood samples, for glucose
      and lipid determinations, were drawn from participants after 12 h of fasting,
      which was followed by a 2-hour oral glucose tolerance test (OGTT) when blood was
      drawn at 0 and 2 h. Insulin resistance was measured by the Quantitative Insulin
      Sensitivity Check Index (QUICKI) method. RESULTS: Suicidal ideation (49 %) and
      previous suicide attempts (16 %) were common in patients with major depressive
      disorder or dysthymia. Patients with depression and suicidal behaviour had higher
      blood glucose concentrations at baseline and at 2 hours in the OGTT. Glucose
      levels associated positively with the prevalence of suicidal behaviour, and the
      linearity was significant at baseline (p for linearity: 0.012, adjusted for age
      and sex) and for 2-hour OGTT glucose (p for linearity: 0.004, adjusted for age
      and sex). QUICKI levels associated with suicidal behavior (p for linearity across
      tertiles of QUICKI: 0.026). Total and LDL cholesterol and triglyceride levels
      were also higher in those patients with suicidal behaviour. Multivariate analysis
      revealed that blood glucose levels, BDI scores and antidepressive medications
      associated with suicidal behaviour. CONCLUSION: Insulin resistance and
      disturbances in glucose and lipid metabolism may be more common in middle-aged
      depressive patients with suicidal behaviour.

PMID- 26199014
TI  - A cross-sectional assessment of quality of life of colorectal cancer patients in
      Saudi Arabia.
AB  - OBJECTIVE: In this cross-sectional study, we aimed to describe the quality of
      life of Saudi colorectal cancer (CRC) patients and identify the factors that may
      further improve health care for CRC survivors in Saudi Arabia (KSA). METHODS: A
      total of 106 CRC patients from five different private and public tertiary level
      hospitals in Saudi Arabia participated in this study. CRC patient was interviewed
      by a trained researcher between September and December 2014. All respondents
      answered a three-part questionnaire which includes demographic data and a
      validated Arabic version of the European Organization for Research and Treatment
      of Cancer (EORTC) Quality of Life. RESULTS: Participants had a mean score for
      global health of 67.1 (95 % CI 62.55-71.71). Among the five scales of quality of
      life, social functioning and functional scales of CRC patients scored the highest
      [Mean 83.49 (95 % CI 78.64-86.33)] while the lowest scored was emotional scales
      [66.9 (95 % CI 61.81-71.98)]. Insomnia was considered the most distressing
      symptom on the symptom scales. Using the disease-specific tool, it was found that
      sexual interest scored the highest. On the symptom scale, dissatisfaction with
      stoma care problems scored the highest. CONCLUSION: Factors associated with a
      major reduction in all domains of quality of life included employment status and
      tumor location. This study identifies the factors and issues that affect the
      quality of life of CRC patients in KSA. Addressing these factors and issues may
      lessen the burden of cancer survivors in the KSA or may prolong their survival.

PMID- 26199015
TI  - miRNA-197 and miRNA-184 are associated with brain metastasis in EGFR-mutant lung
      cancers.
AB  - INTRODUCTION: The prognostic value of EGFR mutation in lung cancer patients with
      brain metastases is uncertain and therapeutic efficacy with EGFR TKI is limited.
      Looking for biomarkers closely related with early tumor changes and brain
      metastases in non-small cell lung cancer is warranted. MicroRNAs (miRNAs) are
      frequently deregulated in lung cancer. The objective of this study was to
      investigate whether some miRNAs are related with brain metastasis risk in EGFR
      mutant non-small cell lung cancer patients. MATERIALS AND METHODS: miRNA
      quantification was retrospectively performed in formalin-fixed, extracranial
      paraffin-embedded adenocarcinoma tumor tissue available from 17 human samples of
      advanced non-small cell lung cancer patients. Samples were classified as brain
      metastasis group (5 EGFR-mutant patients with initial BM, EGFRm-BM+; and 6 EGFR
      wild-type patients with initial BM) and the control group (6 EGFR-mutant NSCLC
      patients without BM). The RNA obtained was preamplified and retro-transcribed,
      and the miRNA was quantified with the TaqMan OpenArray Human MiRNA Panel in the
      QuantStudioTM 12 K Flex Real-Time PCR system. RESULTS: miRNA-197 and miRNA-184
      showed a significant higher expression in EGFRm-BM+ group than in the control
      group (p = 0.017 and p = 0.01, for miRNA-197 and miRNA-184, respectively), with a
      trend toward overexpression in BM group compared with the control group (p = 0.08
      and p = 0.065, for miRNA-197 and miRNA-184, respectively), without differences in
      expression in BM group according to EGFR mutational status (EGFR wild type vs.
      EGFR-mutant: p = 0.175 and p = 0.117, for miRNA-197, miRNA-184 respectively).
      CONCLUSIONS: miRNA-197 and miRNA-184 are overexpressed in EGFR-mutant patients
      with BM and they might be a new biomarker for stratifying the risk of BM in this
      subpopulation.

PMID- 26199016
TI  - Trinucleotide repeat expansions in human breast cancer-susceptibility genes:
      relevant targets for aspirin chemoprevention?
AB  - PURPOSE: Defining novel molecular mechanisms pertinent to aspirin chemoprevention
      of breast cancer (BC) and to explain controversial epidemiological results in
      this regard. METHODS: Literature search in relevant databases with the following
      key words; aspirin, nucleotide repeat expansions, breast cancer. Human genome
      contains nucleotide repeat expansions and exon-1 of the androgen receptor gene AR
      contains a CAG string with an average of 20 repeats. Longer AR CAG repeats
      associate with lower AR protein functioning leading relatively higher estrogen
      receptor signals and higher risk of hormone receptor-positive BC. Nucleotide
      repeat expansions also exist in E2F4 and POLG genes in BC. In cell culture
      models, aspirin reduces CAG.CTG expansions in kidney cells and restores myogenic
      differentiation in cells obtained from tissues with myotonic dystrophy, a
      disorder caused by large CTG expansions. CONCLUSIONS: We hypothesize that aspirin
      reduction of trinucleotide repeat expansions in breast cancer-susceptibility
      genes may be one of the relevant mechanisms of its chemopreventive effects.

PMID- 26199017
TI  - Effectiveness of Minocycline and Rifampin vs Chlorhexidine and Silver
      Sulfadiazine-Impregnated Central Venous Catheters in Preventing Central Line
      Associated Bloodstream Infection in a High-Volume Academic Intensive Care Unit: A
      Before and after Trial.
AB  - BACKGROUND: Use of chlorhexidine and silver sulfadiazine-impregnated (CSS)
      central venous catheters (CVCs) has not been shown to decrease the catheter
      related bloodstream infection rate in an ICU. The purpose of this study was to
      determine if use of minocycline and rifampin-impregnated (MR) CVCs would decrease
      central line-associated bloodstream infection (CLABSI) rates compared with those
      observed with use of CSS-impregnated CVCs. STUDY DESIGN: A total of 7,181
      patients were admitted to a 24-bed university hospital surgical ICU: 2,551
      between March 2004 and August 2005 (period 1) and 4,630 between April 2006 and
      July 2008 (period 2). All patients requiring CVC placement in period 1 had a CSS
      catheter inserted, and in period 2 all patients had MR CVCs placed. RESULTS:
      Twenty-two CLABSIs occurred during 7,732 catheter days (2.7 per 1,000 catheter
      days) in the 18-month period when CSS lines were used. After the introduction of
      MR CVCs, 21 catheter-related bloodstream infections occurred during 15,722
      catheter days (1.4 per 1,000 catheter days). This represents a significant (p <
      0.05) decrease in the CLABSI rate after introduction of MR CVCs. Mean length of
      time to infection developing after catheterization (8.6 days for CSS vs 6.1 days
      for MR) was also different (p = 0.04). The presence of MR did not alter the
      microbiologic profile of catheter-related infections, and it did not increase the
      incidence of resistant organisms. CONCLUSIONS: The CLABSI rate decreased more
      with the use of MR CVCs compared with CSS CVCs in an ICU where the CLABSI rate
      was already low. The types of organisms causing infection were similar. With
      continued use of MR-impregnated CVCs in our ICU in the subsequent 5 years, we
      have seen sustained low rates of CLABSIs.

PMID- 26199018
TI  - Oleanolic acid acrylate elicits antidepressant-like effect mediated by 5-HT1A
      receptor.
AB  - The development of new drugs for the treatment of depression is strategic to
      achieving clinical needs of patients. This study evaluates antidepressant-like
      effect and neural mechanisms of four oleanolic acid derivatives i.e. acrylate
      (D1), methacrylate (D2), methyl fumarate (D3) and ethyl fumarate (D4). All
      derivatives were obtained by simple one-step esterification of oleanolic acid
      prior to pharmacological screening in the forced swimming (FS) and open field
      (OF) tests. Pharmacological tools like alpha-methyl-p-tyrosine (AMPT,
      catecholamine depletor), p-chlorophenylalanine (serotonin depletor), prazosin
      (PRAZ, selective alpha1-receptor antagonist), WAY-100635 (selective serotonin 5
      HT1A receptor antagonist) as well as monoamine oxidase (MAO) and functional
      binding assays were conducted to investigate possible neural mechanisms. In the
      FS test, D1 showed the most promising antidepressant-like effect without
      eliciting locomotor incoordination. Unlike group of mice pretreated with AMPT 100
      mg/kg, PCPA 100 mg/kg or PRAZ 1 mg/kg, the effect of D1 was attenuated by WAY
      100635 0.3 mg/kg pretreatment. D1 demonstrated moderate inhibition of MAO-A (IC50
      = 48.848 +/- 1.935 MUM), potency (pEC50 = 6.1 +/- 0.1) and intrinsic activity (E
      max = 26 +/- 2.0%) on 5-HT1A receptor. In conclusion, our findings showed
      antidepressant-like effect of D1 and possible involvement of 5-HT1A receptor.

PMID- 26199023
TI  - Wendell Berry--health is membership.

PMID- 26199022
TI  - Metabolic syndrome and the short-term prognosis of acute ischemic stroke: a
      hospital-based retrospective study.
AB  - BACKGROUND: Metabolic syndrome (MetS) is an important risk factor for cerebral
      ischemic stroke, yet previous studies on the relationship between MetS or its
      components and acute cerebral infarction have been inconsistent. This study aims
      to evaluate the effects of MetS and its components on the short-term prognosis of
      patients with acute ischemic stroke. METHODS: Subjects with ischemic stroke of <7
      day duration (530 cases) were enrolled. MetS was defined based on the modified
      criteria of the International Diabetes Federation and the American Heart
      Association/National Heart, Lung, and Blood Institute. Demographic data, vascular
      risk factors, National Institutes of Health Stroke Scale score, the results of
      physical, laboratory and imaging examinations and clinical outcomes at 30 and 90
      days were recorded. Using univariate analysis, we compared different baseline
      characteristics between patients with MetS and those without MetS. Further, we
      assessed MetS and its 5 components on the contribution to short-term prognosis of
      ischemic stroke with multiple logistic regression models after adjusting for age
      and sex. RESULTS: The prevalence of MetS among the patients with acute ischemic
      stroke in the study is 58.3%, with more in females (70.3%) than in males (49.7%,
      p < 0.001). As expected, among the MetS components, elevated waist circumference,
      elevated triglyceride, high fasting blood glucose and low high density
      lipoprotein cholesterol (HDL-C) were significantly more prevalent in patients
      with MetS than those without MetS (all p < 0.001). There was no correlation
      between MetS itself and the short-term prognosis of acute ischemic stroke. Only
      hyperglycemia in the serum was shown to have impact on poor functional outcomes
      in 30 and 90 days after the onset of stroke. CONCLUSIONS: The occurrence of MetS
      among patients with acute ischemic stroke in our study is 58.3%. MetS itself may
      not be predictive for the short-term prognosis of patients, while hyperglycemia
      is a significant predictor for poor functional outcomes in our study.

PMID- 26199024
TI  - In vivo evaluation of a modified linear stapling device designed to facilitate
      accurate pathologic examination of the surgical margin.
AB  - BACKGROUND: Microscopic involvement of the resection margin could influence the
      long-term outcome of patients undergoing curative surgery for gastric cancer.
      Linear staplers, commonly used for gastrectomies, are often equipped with three
      lines of staples on either side of the resection line. Although multiple lines of
      staples reinforce closure of the gastric or intestinal stump, they could hinder
      accurate histopathologic evaluation of the surgical margin of the resected
      specimen. METHODS: We modified a linear stapling device by removing one line
      (stapler E2) or two lines (stapler E1) of staples on the specimen side, and
      attempted to dissect a silicon film and then the stomach from a porcine model
      using the stapling device and examined the distances between the cutting edge and
      the nearest staple line. RESULTS: The distance between the cutting edge and the
      staple line for stapler E1 was significantly greater than the distance between
      the cutting edge and the nearest staple line for stapler E2 or the control
      device. Consequently, specimens of exemplary quality were available for
      pathologic examination of the surgical margin. Moreover, the lack of multiple
      layers of staples did not result in contamination of the abdominal cavity with
      gastric juice during laparoscopic procedures in the porcine model. CONCLUSIONS:
      Stapler E1 is safe and could be useful for the pathologic evaluation of the true
      surgical margin.

PMID- 26199025
TI  - Laparoscopic pancreatic resection.
AB  - Though initially slow to gain acceptance, the minimally invasive approach to
      pancreatic resection grew during the last decade and pancreatic operations such
      as the distal pancreatectomy and pancreatic enucleation are frequently performed
      laparoscopically. More complex operations such as the pancreaticoduodenectomy may
      also confer benefits with a minimally invasive approach but are less widely
      utilized. Though most research to date comparing open and laparoscopic
      pancreatectomy is retrospective, the current data suggest that compared with
      open, a laparoscopic procedure may afford postoperative benefits such as less
      blood loss, shorter hospital stay, and fewer wound complications. Regarding
      oncologic considerations, despite initial concerns, laparoscopic resection
      appears to be non-inferior to an open procedure in terms of lymph node retrieval,
      negative margin rates, and long-term survival. New technologies, such as
      robotics, are also gaining acceptance. Data show that while the laparoscopic
      approach incurs higher cost in the operating room, the resulting shorter hospital
      stay appears to be associated with an equivalent or lower overall cost. The
      minimally invasive approach to pancreatic resection can be safe and appropriate
      with significant patient benefits and oncologic non-inferiority based on existing
      data. 

PMID- 26199026
TI  - A visual servo-based teleoperation robot system for closed diaphyseal fracture
      reduction.
AB  - Common fracture treatments include open reduction and intramedullary nailing
      technology. However, these methods have disadvantages such as intraoperative X
      ray radiation, delayed union or nonunion and postoperative rotation. Robots
      provide a novel solution to the aforementioned problems while posing new
      challenges. Against this scientific background, we develop a visual servo-based
      teleoperation robot system. In this article, we present a robot system, analyze
      the visual servo-based control system in detail and develop path planning for
      fracture reduction, inverse kinematics, and output forces of the reduction
      mechanism. A series of experimental tests is conducted on a bone model and an
      animal bone. The experimental results demonstrate the feasibility of the robot
      system. The robot system uses preoperative computed tomography data to realize
      high precision and perform minimally invasive teleoperation for fracture
      reduction via the visual servo-based control system while protecting surgeons
      from radiation. 

PMID- 26199028
TI  - Comparing general and spinal anaesthesia for hip fracture surgery.

PMID- 26199027
TI  - Pathogenesis of Arrhythmogenic Cardiomyopathy.
AB  - Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease. It is
      characterized by frequent ventricular arrhythmias and increased risk of sudden
      cardiac death typically arising as an early manifestation before the onset of
      significant myocardial remodelling. Myocardial degeneration, often confined to
      the right ventricular free wall, with replacement by fibrofatty scar tissue,
      develops in many patients. ACM is a familial disease but genetic penetrance can
      be low and disease expression is highly variable. Inflammation might promote
      disease progression. It also appears that exercise increases disease penetrance
      and accelerates its development. More than 60% of probands harbour mutations in
      genes that encode desmosomal proteins, which has raised the possibility that
      defective cell-cell adhesion might play a role in disease pathogenesis. Recent
      advances have implicated changes in the canonical wingless-type mouse mammary
      tumour virus integration site (Wnt)/beta-catenin and Hippo signalling pathways
      and defects in forwarding trafficking of ion channels and other proteins to the
      intercalated disk in cardiac myocytes. In this review we summarize the current
      understanding of the pathogenesis of ACM and highlight future research
      directions. 

PMID- 26199029
TI  - Use of the initial trauma CT scan to aid in diagnosis of open pelvic fractures.
AB  - Open pelvic disruptions represent high-energy injuries. The prompt identification
      and management of these injuries decreases their associated morbidity and
      mortality. Computed tomography (CT) scans are routinely obtained in the initial
      evaluation of patients with pelvic injuries. The purpose of this study is to
      identify the incidence and source of air densities noted on computed tomography
      (CT) scans of the abdominal and pelvic region in patients with pelvic fractures
      and evaluate the use of initial CT imaging as an adjunctive diagnostic tool to
      identify open injuries. A retrospective review of a prospectively collected
      database was performed at a single institution. Seven hundred and twenty-two
      consecutive patients with a pelvic disruption over a two-year period were
      included. Review of initial injury CT scans was performed using bone and lung
      viewing algorithms to identify the presence of extra-luminal air. The primary
      outcome was the presence, location and source of air identified on pre-operative
      CT scans. Secondary measurements were identification of air by plain radiograph
      and correlation between identified air densities on CT and clinically diagnosed
      open pelvic fractures. Ninety-eight patients were identified as having extra
      luminal air densities on CT scans. Eighty-one patients were included in the final
      analysis following application of inclusion and exclusion criteria. Air was noted
      by the radiologist in forty-five (55.6%) instances. Six patients (7.4%) were
      clinically diagnosed with an open pelvic ring disruption; in two patients (2.4%)
      this diagnosis was delayed. In all patients, the CT was able to track air from
      its origin. In patients with pelvic disruptions, the injury CT should also be
      evaluated for the presence and source of extra-luminal air. In some patients,
      this finding may represent an open pelvic ring disruption. A complete physical
      exam and CT evaluation should be used to decrease the missed or delayed diagnosis
      of an open pelvic ring injury. 

PMID- 26199030
TI  - How much articular displacement can be detected using fluoroscopy for tibial
      plateau fractures?
AB  - INTRODUCTION: While there is conflicting evidence regarding the importance of
      anatomic reduction for tibial plateau fractures, there are currently no studies
      that analyse our ability to grade reduction based on fluoroscopic imaging. The
      purpose of this study was to determine the accuracy of fluoroscopy in judging
      tibial plateau articular reduction. METHODS: Ten embalmed human cadavers were
      selected. The lateral plateau was sagitally sectioned, and the joint was reduced
      under direct visualization. Lateral, anterior-posterior (AP), and joint line
      fluoroscopic views were obtained. The same fluoroscopic views were obtained with
      2mm displacement and 5mm displacement. The images were randomised, and eight
      orthopaedic traumatologists were asked whether the plateau was reduced. Within
      each pair of conditions (view and displacement from 0mm to 5mm) sensitivity,
      specificity, and intraclass correlations (ICC) were evaluated. RESULTS: The AP
      lateral view with 5mm displacement yielded the highest accuracy for detecting
      reduction at 90% (95% CI: 83-94%). For the other conditions, accuracy ranged from
      (37-83%). Sensitivity was highest for the reduced lateral view (79%, 95% CI: 57
      91%). Specificity was highest in the AP-lateral view 98% (95% CI: 93-99%) for 5mm
      step-off. ICC was perfect for the AP-lateral view with 5mm displacement, but
      otherwise agreement ranged from poor to moderate at ICC=0.09-0.46. Finally, there
      was no additional benefit to including the joint-line view with the AP and
      lateral views. CONCLUSION: Using both AP and lateral views for 5mm displacement
      had the highest accuracy, specificity, and ICC. Outside of this scenario,
      agreement was poor to moderate and accuracy was low. Applying this clinically,
      direct visualization of the articular surface may be necessary to ensure
      malreduction less than 5mm.

PMID- 26199032
TI  - A new aspect of cyclopentadithiophene based polymers: narrow band gap polymers
      upon protonation.
AB  - A new aspect of cyclopentadithiophene (CPDT) based conjugated polymers was
      reported. CPDT units in conjugated polymers can be facilely protonated with a
      significant change in optical and electronic properties. The protonation was
      confirmed by NMR spectra studies and the remarkable decrease of the energy band
      gap was attributed to charge separation upon protonation.

PMID- 26199031
TI  - Redox stress unbalances the inflammatory cytokine network: role in
      autoinflammatory patients and healthy subjects.
AB  - The cell stress and redox responses are increasingly acknowledged as factors
      contributing to the generation and development of the inflammatory response.
      Several inflammation-inducing stressors have been identified, inside and outside
      of the cell. Furthermore, many hereditary diseases associate with inflammation
      and oxidative stress, suggesting a role for mutated proteins as stressors. The
      nucleotide-binding oligomerization domain, leucine-rich repeat-containing family,
      pyrin domain-containing 3 (NLRP3) inflammasome is an important node at the
      crossroad between redox response and inflammation. Remarkably, monocytes from
      patients with mutations in the NLRP3 gene undergo oxidative stress after
      stimulation with minute amounts of TLR agonists, resulting in unbalanced
      production of IL-1beta and regulatory cytokines. Similar alterations in cytokine
      production are found in healthy monocytes upon TLR overstimulation. This mini
      review summarizes recent progress in this field, discusses the molecular
      mechanisms underlying the loss of control of the cytokine network following
      oxidative stress, and proposes new therapeutic opportunities. 

PMID- 26199033
TI  - [Distal soft-tissue procedure in hallux valgus deformity].
AB  - OBJECTIVE: Distal, lateral soft tissue release to restore mediolateral balance of
      the first metatarsophalangeal (MTP) joint in hallux valgus deformity. Incision of
      the adductor hallucis tendon from the fibular sesamoid, the lateral capsule, the
      lateral collateral ligament, and the lateral metatarsosesamoid ligament.
      INDICATIONS: Hallux valgus deformities or recurrent hallux valgus deformities
      with an incongruent MTP joint. CONTRAINDICATIONS: General medical
      contraindications to surgical interventions. Painful stiffness of the MTP joint,
      osteonecrosis, congruent joint. Relative contraindications: connective tissue
      diseases (Marfan syndrome, Ehler-Danlos syndrome). SURGICAL TECHNIQUE:
      Longitudinal, dorsal incision in the first intermetatarsal web space between the
      first and second MTP joint. Blunt dissection and identification of the adductor
      hallucis tendon. Release of the adductor tendon from the fibular sesamoid.
      Incision of the lateral capsule, the lateral collateral ligament, and the lateral
      metatarsosesamoid ligament. POSTOPERATIVE MANAGEMENT: Postoperative management
      depends on bony correction. In joint-preserving procedures, dressing for 3 weeks
      in corrected position. Subsequently hallux valgus orthosis at night and a toe
      spreader for a further 3 months. Passive mobilization of the first MTP joint.
      Postoperative weight-bearing according to the osteotomy. RESULTS: A total of 31
      patients with isolated hallux valgus deformity underwent surgery with a Chevron
      and Akin osteotomy and a distal medial and lateral soft tissue balancing. The
      mean preoperative intermetatarsal (IMA) angle was 12.3 degrees  (range 11-15
      degrees ); the hallux valgus (HV) angle was 28.2 degrees  (25-36 degrees ). The
      mean follow-up was 16.4 months (range 12-22 months). The mean postoperative IMA
      correction ranged between 2 and 7 degrees  (mean 5.2 degrees ); the mean HV
      correction was 15.5 degrees  (range 9-21 degrees ). In all, 29 patients (93%)
      were satisfied or very satisfied with the postoperative outcome, while 2 patients
      (7%) were not satisfied due to one delayed wound healing and one recurrent hallux
      valgus deformity. There were no infections, clinical and radiological signs of
      avascular necrosis of the metatarsal head, overcorrection with hallux varus
      deformity, or significant stiffness of the first MTP joint.

PMID- 26199036
TI  - A Novel Technique for Repositioning of a Migrated ILUVIEN((r)) (Fluocinolone
      Acetonide) Implant into the Anterior Chamber.
AB  - INTRODUCTION: Fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN((r));
      Alimera Sciences Limited, Aldershot, UK) has been approved in the UK for the
      treatment of chronic diabetic macula edema, insufficiently responsive to
      available therapies. It is inserted into the vitreous cavity through a 25-gauge
      needle. Migration of the implant to the anterior chamber (AC) can occur through
      gaps in the posterior capsule especially in vitrectomized eyes. Early removal of
      AC-dislocated FAc implant is essential to prevent corneal edema and damage from
      raised intraocular pressure. AIM: To demonstrate a simple and novel technique,
      with a previous capsular tear, for removal of AC-migrated FAc implant and
      reinsertion into the vitreous cavity without compromising implant integrity.
      METHOD: A side port incision was created with a keratome and an anterior chamber
      maintainer introduced and secured. Subsequently, a corneal incision was created
      at 12 o'clock through which a 23-gauge backflush needle (flute needle) was
      advanced into the anterior chamber and passive suction used to secure the
      implant. The flute needle was then placed through the defect in the posterior
      capsule and the exit port blocked, causing loss of suction and allowing the
      implant to fall into the posterior segment. The sulcus intraocular lens (IOL) was
      centralized simply by manipulating it approximately 180 degrees to provide
      adequate anterior capsule support. RESULTS: The FAc implant was successfully
      removed from AC in two patients and reinserted into the vitreous cavity without
      damage or complications either for the eye or the implant. IOL in both patients
      were repositioned to close the gap in posterior capsule. After 2 months, the
      implant remains in the vitreous cavity. This paper presents data from one of
      these cases. CONCLUSION: Using 23-gauge flute needle to retrieve dislocated FAc
      implant is a safe and easy technique. FUNDING: Alimera Sciences Ltd.

PMID- 26199034
TI  - [Dwyer osteotomy : Lateral sliding osteotomy of calcaneus].
AB  - OBJECTIVE: To correct the underlying inframalleolar varus deformity and to
      restore physiologic biomechanics of the hindfoot. INDICATIONS: Neurologic,
      posttraumatic, congenital, and idiopathic cavovarus deformity. In patients with
      end-stage ankle osteoarthritis with varus heel malposition as additional single
      stage procedure complementing total ankle replacement. Severe peroneal
      tendinopathy with concomitant cavovarus deformity. CONTRAINDICATIONS: General
      surgical or anesthesiological risks, infections, critical soft tissue conditions,
      nonmanageable hindfoot instability, neurovascular impairment of the lower
      extremity, neuroarthropathy (e. g., Charcot arthropathy), end-stage
      osteoarthritis of the subtalar joint, severely reduced bone quality, high age,
      insulin-dependent diabetes mellitus, smoking. SURGICAL TECHNIQUE: The lateral
      calcaneus cortex is exposed using a lateral incision. The osteotomy is performed
      through an oscillating saw. The posterior osteotomy fragment is manually
      mobilized and shifted laterally. If needed, a laterally based wedge can be
      removed and/or the osteotomy fragment can be translated cranially. The osteotomy
      is stabilized with two cannulated screws, followed by wound closure.
      POSTOPERATIVE MANAGEMENT: A soft wound dressing is used. Thromboprophylaxis is
      recommended. Patient mobilization starts on postoperative day 1 with 15 kg
      partial weight bearing using a stabilizing walking boot or cast for 6 weeks.
      Following clinical and radiographic follow-up at 6 weeks, full weight bearing is
      initiated step by step. RESULTS: Between January 2009 and June 2013, a Dwyer
      osteotomy was performed in 31 patients with a mean age of 45.7 +/- 16.3 years
      (range 21.5-77.4 years). All patients had a substantial inframalleolar cavovarus
      deformity with preoperative moment arm of the calcaneus of -17.9 +/- 3.3 mm
      (range -22.5 to -10.5 mm), which has been improved significantly to 1.6 +/- 5.9
      mm (range -16.9 to 9.9 mm). Significant pain relief from 6.3 +/- 1.9 (range 4-10)
      to 1.1 +/- 1.1 (range 0-4) using the visual analogue scale was observed. The
      American Orthopaedic Foot and Ankle Society score significantly improved from
      33.1 +/- 14.2 (range 10-60) to 78.0 +/- 10.5 (range 55-95).

PMID- 26199038
TI  - Strain engineering in semiconducting two-dimensional crystals.
AB  - One of the fascinating properties of the new families of two-dimensional crystals
      is their high stretchability and the possibility to use external strain to
      manipulate, in a controlled manner, their optical and electronic properties.
      Strain engineering, understood as the field that study how the physical
      properties of materials can be tuned by controlling the elastic strain fields
      applied to it, has a perfect platform for its implementation in the atomically
      thin semiconducting materials. The object of this review is to give an overview
      of the recent progress to control the optical and electronics properties of 2D
      crystals, by means of strain engineering. We will concentrate on semiconducting
      layered materials, with especial emphasis in transition metal dichalcogenides
      (MoS2, WS2, MoSe2 and WSe2). The effect of strain in other atomically thin
      materials like black phosphorus, silicene, etc, is also considered. The benefits
      of strain engineering in 2D crystals for applications in nanoelectronics and
      optoelectronics will be revised, and the open problems in the field will be
      discussed. 

PMID- 26199037
TI  - Controversies in the Management of Vesicoureteral Reflux.
AB  - Vesicoureteral reflux (VUR) is the abnormal retrograde flow of urine from the
      bladder into the upper urinary tract. Diagnosis and subsequent management of VUR
      have become increasingly controversial, with differing opinions over which
      children should be evaluated for reflux, and when detected, who should undergo
      treatment. Management goals include prevention of recurrent febrile urinary tract
      infection (fUTI) and renal injury while minimizing the morbidity of treatment and
      follow-up. Management options include observation with or without continuous
      antibiotic prophylaxis and surgical correction via endoscopic, open or
      laparoscopic/robotic approaches. Management should be individualized and based on
      patient age, health, risk of subsequent renal injury, clinical course, renal
      function, and parental preference. 

PMID- 26199041
TI  - Multiple periradicular radiolucencies mimicking endodontic lesions in renal
      osteodystrophy of the mandible: a case report.
AB  - AIM: To report a finding of multiple periapical radiolucencies mimicking
      endodontic lesions in a patient with renal osteodystrophy of the mandible.
      SUMMARY: A 47-year-old woman was referred by her general dentist to the
      postgraduate endodontic clinic for assessment and root canal treatment of
      multiple teeth with associated periapical radiolucencies. The patient's medical
      history included chronic renal failure. All mandibular teeth with periapical
      radiolucencies except tooth 37 had positive responses to pulp sensibility
      testing. A diagnosis of pulpal necrosis and associated periapical periodontitis
      was made on tooth 37, and root canal treatment was carried out. To determine the
      possible relationship between the patient's renal disease and the multiple
      periapical radiolucencies, an additional physician consultation and laboratory
      tests were requested. Secondary hyperparathyroidism was confirmed with the
      laboratory report showing an elevated level of parathyroid hormone and a normal
      serum calcium level. Renal osteodystrophy of the mandible caused by secondary
      hyperparathyroidism was the probable aetiology of the multiple mandibular
      periapical radiolucencies, and no root canal treatment was required. Key learning
      points Renal osteodystrophy of the mandible caused by secondary
      hyperparathyroidism can present as multiple periapical radiolucencies but is a
      rare finding. Diverse orofacial manifestations such as loss of lamina dura,
      widening of periodontal ligament and demineralization of bone can be observed in
      renal osteodystrophy. Thorough clinical and radiographic assessment along with
      the review of patient's medical history and haematological analysis is essential
      for the diagnosis of renal osteodystrophy.

PMID- 26199040
TI  - Central cholinergic dysfunction could be associated with oropharyngeal dysphagia
      in early Parkinson's disease.
AB  - Dysphagia is an important issue in the prognosis of Parkinson's disease (PD).
      Although several studies have reported that oropharyngeal dysphagia may be
      associated with cognitive dysfunction, the exact relationship between cortical
      function and swallowing function in PD patients is unclear. Therefore, we
      investigated the association between an electrophysiological marker of central
      cholinergic function, which reflected cognitive function, and swallowing
      function, as measured by videofluoroscopic studies (VFSS). We enrolled 29 early
      PD patients. Using the Swallowing Disturbance Questionnaire (SDQ), we divided the
      enrolled patients into two groups: PD with dysphagia and PD without dysphagia.
      The videofluoroscopic dysphagia scale (VDS) was applied to explore the nature of
      the dysphagia. To assess central cholinergic dysfunction, short latency afferent
      inhibition (SAI) was evaluated. We analyzed the relationship between central
      cholinergic dysfunction and oropharyngeal dysphagia and investigated the
      characteristics of the dysphagia. The SAI values were significantly different
      between the two groups. The comparison of each VFSS component between the PD with
      dysphagia group and the PD without dysphagia group showed statistical
      significance for most of the oral phase components and for a single pharyngeal
      phase component. The total score on the VDS was higher in the PD with dysphagia
      group than in the PD without dysphagia group. The Mini-Mental State Examination
      and SAI values showed significant correlations with the total score of the oral
      phase components. According to binary logistic regression analysis, SAI value
      independently contributed to the presence of dysphagia in PD patients. Our
      findings suggest that cholinergic dysfunction is associated with dysphagia in
      early PD and that an abnormal SAI value is a good biomarker for predicting the
      risk of dysphagia in PD patients. 

PMID- 26199039
TI  - Results of a phase 1 trial combining ridaforolimus and MK-0752 in patients with
      advanced solid tumours.
AB  - BACKGROUND: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target
      of rapamycin (PI3K-AKT-mTOR) signalling pathway is aberrantly activated in
      several cancers. Notch signalling maintains cell proliferation, growth and
      metabolism in part by driving the PI3K pathway. Combining the mTOR inhibitor
      ridaforolimus with the Notch inhibitor MK-0752 may increase blockade of the PI3K
      pathway. METHODS: This phase I dose-escalation study (NCT01295632) aimed to
      define the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of
      combination oral ridaforolimus (rising doses starting at 20 mg, 5 days/week) and
      oral MK-0752 (1800 mg once weekly) in patients with solid tumours. No
      intrapatient dose escalation was permitted. RESULTS: Twenty eight patients were
      treated on study. Ridaforolimus doses were escalated from 20 to 30 mg/day. Among
      14 evaluable patients receiving ridaforolimus 20 mg, one DLT (grade 2 stomatitis,
      second episode) was reported. Among eight evaluable patients receiving
      ridaforolimus 30 mg, three DLTs were reported (one each grade 3 stomatitis, grade
      3 diarrhoea, and grade 3 asthenia). The MTD was 20 mg daily ridaforolimus 5
      days/week+1800 mg weekly MK-0752. The most common drug-related adverse events
      included stomatitis, diarrhoea, decreased appetite, hyperglycaemia,
      thrombocytopenia, asthenia and rash. Two of 15 (13%) patients with head and neck
      squamous cell carcinoma (HNSCC) had responses: one with complete response and one
      with partial response. In addition, one patient experienced stable disease ?6
      months. CONCLUSIONS: Combined ridaforolimus and MK-0752 showed activity in HNSCC.
      However, a high number of adverse events were reported at the MTD, which would
      require careful management during future clinical development.

PMID- 26199042
TI  - Perioperative Hyperglycemia and Glucose Variability in Gynecologic Laparotomies.
AB  - BACKGROUND: The glycemic response and its relation to postoperative complications
      following gynecologic laparotomies is unknown, although these surgeries carry a
      substantial risk for postoperative morbidity. Therefore, our objective was to
      assess the prevalence of perioperative hyperglycemia and glucose variability in
      women undergoing a gynecologic laparotomy. METHODS: In this prospective cohort
      study, capillary glucose was measured every hour during the perioperative period.
      The primary outcome measures were the proportion of patients with postoperative
      hyperglycemia (glucose >180 mg d l(-1)) and the glucose variability in the intra-
      and postoperative period. Postoperative complications were assessed as secondary
      outcome measure. RESULTS: We included 150 women undergoing a gynecologic
      laparotomy. Perioperative hyperglycemia occurred in 33 patients without diabetes
      (23.4%) and in 8 patients with diabetes (89%). Glucose variability was
      significantly higher (mean absolute glucose change [MAG] 11 mg dl(-1) hr(-1) [IQR
      8-18]) in the intraoperative compared to the postoperative period (MAG 10 mg dl(
      1) hr(-1) [IQR 3-16], P = .03). Neither hyperglycemia nor glucose variability was
      associated with postoperative complications. CONCLUSIONS: Hyperglycemia and
      glucose variability seem to be a minor problem during gynecologic laparotomy.
      Based on the current data, we would not advocate standardized glucose
      measurements in every patient without diabetes undergoing gynecologic laparotomy.

PMID- 26199043
TI  - Mineral content of the maternal diet influences ectopic mineralization in
      offspring of Abcc6(-/-) mice.
AB  - Ectopic mineralization disorders inflicting the connective tissues display a
      spectrum of severity, some developing in utero and being diagnosed by prenatal
      ultrasound. This study was designed to test the hypothesis that the mineral
      content of maternal diet can influence the mineralization in the offspring.
      Pregnant Abcc6(-/-) mice, on 2 different strain backgrounds, were maintained
      either on normal rodent diet or on "acceleration diet," rich in phosphate and low
      in magnesium, which has been previously shown to enhance the mineralization
      processes. The offspring were examined for mineralization by histopathology of
      various tissues and quantitated by chemical assay of calcium. The ectopic
      mineralization in the dermal sheath of vibrissae, a progressive biomarker of the
      overall mineralization, was readily detectable at the age of 4 weeks in the pups
      whose mothers were on the acceleration diet, while no evidence of mineralization
      was noted in those on normal diet. The mineralization of the vibrissae
      progressively increased when examined at 12 weeks of age. There was a significant
      reduction in urinary calcium and significant increase in urinary phosphorus
      concentrations both at 4 and 12 weeks of age in mice on the acceleration diet as
      compared to those on control diet. The results demonstrate that the mineral
      content of the maternal diet can influence ectopic mineralization in the
      offspring of mice genetically predisposed to ectopic mineralization (Abcc6(-/-)).
      These observations have implications for dietary management of pregnancies in
      which the fetus is diagnosed by prenatal ultrasound to have an ectopic
      mineralization disorder.

PMID- 26199044
TI  - [The abdominal aortic aneurysm].

PMID- 26199045
TI  - Using a Virtual Environment to Deliver Evidence-Based Interventions: The
      Facilitator's Experience.
AB  - BACKGROUND: Evidence-based interventions (EBIs) have the potential to maximize
      positive impact on communities. However, despite the quantity and quality of EBIs
      for prevention, the need for formalized training and associated training-related
      expenses, such as travel costs, program materials, and input of personnel hours,
      pose implementation challenges for many community-based organizations. In this
      study, the community of inquiry (CoI) framework was used to develop the virtual
      learning environment to support the adaptation of the !Cuidate! (Take Care of
      Yourself!) Training of Facilitators curriculum (an EBI) to train facilitators
      from community-based organizations. OBJECTIVE: The purpose of this study was to
      examine the feasibility of adapting a traditional face-to-face facilitator
      training program for !Cuidate!, a sexual risk reduction EBI for Latino youth, for
      use in a multi-user virtual environment (MUVE). Additionally, two aims of the
      study were explored: the acceptability of the facilitator training and the level
      of the facilitators' knowledge and self-efficacy to implement the training.
      METHODS: A total of 35 facilitators were trained in the virtual environment. We
      evaluated the facilitators' experience in the virtual training environment and
      determined if the learning environment was acceptable and supported the
      acquisition of learning outcomes. To this end, the facilitators were surveyed
      using a modified community of inquiry survey, with questions specific to the
      Second Life environment and an open-ended questionnaire. In addition, a
      comparison to face-to-face training was conducted using survey methods. RESULTS:
      Results of the community of inquiry survey demonstrated a subscale mean of 23.11
      (SD 4.12) out of a possible 30 on social presence, a subscale mean of 8.74 (SD
      1.01) out of a possible 10 on teaching presence, and a subscale mean of 16.69 (SD
      1.97) out of a possible 20 on cognitive presence. The comparison to face-to-face
      training showed no significant differences in participants' ability to respond to
      challenging or sensitive questions (P=.50) or their ability to help participants
      recognize how Latino culture supports safer sex (P=.32). There was a significant
      difference in their knowledge of core elements and modules (P<.001). A total of
      74% (26/35) of the Second Life participants did agree/strongly agree that they
      had the skills to deliver the !Cuidate! CONCLUSIONS: The results showed that
      participants found the Second Life environment to be acceptable to the learners
      and supported an experience in which learners were able to acquire the knowledge
      and skills needed to deliver the curriculum.

PMID- 26199046
TI  - Single and combined effects of body composition phenotypes on carotid intima
      media thickness.
AB  - BACKGROUND: Central fatness might be a more sensitive predictor of
      atherosclerotic changes in children than are total body fat measures. However, it
      is unclear whether a total body fat measure coupled with an estimate of a more
      central pattern of fat accumulation predicts increased carotid intima-media
      thickness (cIMT) better than either measure alone. OBJECTIVE: The objective of
      the study is to identify the ability of a combination of simple anthropometric
      screening tools or a combination of objective measures of body composition to
      predict cIMT. METHODS: cIMT was assessed on the common carotid artery in 349
      children aged 11-12 years old (183 girls). Body mass index (BMI), waist
      circumference (WC) and waist-to-height ratio (WHtR) were dichotomized according
      to established criteria and indices of total body (TBFI) and abdominal (ABFMI)
      fat were assessed by dual-energy X-ray absorptiometry and categorized (increased
      risk >=85%). Single and combined associations among anthropometric and
      laboratorial measures with the risk of having increased cIMT (>=85%) and
      discriminatory performance were tested with logistic regression analysis and
      Receiver Operator Curve analysis. RESULTS: Children with higher total fatness
      (BMI and TBFI) or higher central pattern of fat accumulation (WC, WHtR and BFMI)
      were in higher risk for increased cIMT [odds ratio (OR): 2.08-3.24). The risk for
      increased cIMT was not higher among children who coupled high total and high
      central fatness (OR: 2.27-3.10). CONCLUSIONS: Combination of total and central
      measures of fat does not improve the prediction of increased cIMT in children.
      Simple surrogate measures of fatness can be used to predict increased cIMT urging
      special attention to those children who exhibit increased abdominal fat.

PMID- 26199047
TI  - Evolutionary pathway of pseudogenization of globin genes, alpha5 and beta5, in
      genus Oryzias.
AB  - Hemoglobin transports oxygen in many organisms and consists of alpha- and beta
      globin chains. Previously, using molecular phylogenetic analysis, we proposed
      that both alpha- and beta-globins of teleost could be classified into four
      groups. We also showed that the Hd-rR strain of medaka (Oryzias latipes)
      inhabiting southern Japan had all four groups of globin genes but that the alpha-
      and beta-globin genes of group III were pseudogenized (alpha5(psialpha),
      beta5(psibeta)). Based on the small degree of nucleotide variations, the
      pseudogenization of beta5 was assumed to have occurred at a relatively late stage
      of evolution. Here, we compared the alpha5(psialpha)-beta5(psibeta) of two other
      strains of O. latipes and found that both alpha5(psialpha) and beta5(psibeta) of
      the northern Japanese and Korean strains were pseudogenized similar to those of
      Hd-rR. In a Philippine population (Oryzias luzonensis), alpha5(psialpha) was also
      pseudogenized, but the structure was different from that of O. latipes, and
      beta5(psibeta) was almost deleted. Interestingly, an Indonesian population
      (Oryzias celebensis) had alpha5 and beta5 genes that were deduced to be
      functional. Indeed, they were expressed from the young to adult development
      stages, and this expression pattern was consistent with the expression of alpha2
      and ad.alpha1 in Hd-rR. Because alpha2 and ad.alpha1 in Hd-rR were assigned to
      groups I and II, respectively, we speculate that their expression patterns might
      be altered by pseudogenization of group III genes. These results provide a basis
      for further investigations of recruiting and changing expression patterns of one
      globin gene after pseudogenization of other globin genes during evolution.

PMID- 26199048
TI  - Potential correlations of dentogenic factors to the development of clinically
      verified fungus balls: A retrospective computed tomography-based analysis.
AB  - OBJECTIVES/HYPOTHESIS: Fungus balls are a common disease of the paranasal
      sinuses, usually involving the maxillary sinus. To clarify the pathology, we
      analyzed patients treated for maxillary sinus fungus balls to see whether the
      latter correlated with dentogenic factors. STUDY DESIGN: Retrospective case
      analysis. METHODS: Cases of maxillary sinus fungus balls diagnosed between
      January 2000 and December 2013 were analyzed retrospectively. Patients' charts
      were reviewed for diagnosis, gender, and age. Paranasal sinus computed tomography
      (CT) scans were reviewed according to the side of the fungus ball,
      calcifications/opacifications, and dentogenic factors. RESULTS: In 98/102
      patients (96.1%), 157 dentogenic factors could be identified on the side affected
      by a fungus ball. On the contralateral healthy side, there were 125 dentogenic
      factors. In four (3.9%) of the patients, no dentogenic pathology was identified
      on the CT scan. The presence of dentogenic factors (regardless of number) was
      significantly associated with a fungus ball compared to the healthy side (P =
      .024, chi(2) test, odds ratio: 2.72 [95% confidence interval: 1.02-7.23]).
      CONCLUSIONS: Dentogenic factors regardless of type potentially correlate with the
      presence of maxillary sinus fungus ball. Unlike the overall presence of
      dentogenic factors, the particular dentogenic factors in an individual patient do
      not significantly influence the development of fungus balls. After diagnosis of
      dentogenic pathology in penetrated maxillary sinus floors, patients should be
      closely monitored and informed about their higher risk of developing a fungus
      ball.

PMID- 26199049
TI  - Assembly of light-emitting diode based on hydrophilic CdTe quantum dots
      incorporating dehydrated silica gel.
AB  - Stable photoluminescence QD light-emitting diodes (QD-LEDs) were made based on
      hydrophilic CdTe quantum dots (QDs). A quantum dot-inorganic nanocomposite
      (hydrophilic CdTe QDs incorporating dehydrated silica gel) was prepared by two
      methods (rotary evaporation and freeze drying). Taking advantage of its
      viscosity, plasticity and transparency, dehydrated silica gel could be coated on
      the surface of ultraviolet (UV) light LEDs to make photoluminescence QD-LEDs.
      This new photoluminescence QD-LED, which is stable, environmentally non-toxic,
      easy to operate and low cost, could expand the applications of hydrophilic CdTe
      QDs in photoluminescence.

PMID- 26199050
TI  - Erratum.

PMID- 26199051
TI  - Interaction-induced decay of a heteronuclear two-atom system.
AB  - Two-atom systems in small traps are of fundamental interest for understanding the
      role of interactions in degenerate cold gases and for the creation of quantum
      gates in quantum information processing with single-atom traps. One of the key
      quantities is the inelastic relaxation (decay) time when one of the atoms or both
      are in a higher hyperfine state. Here we measure this quantity in a heteronuclear
      system of (87)Rb and (85)Rb in a micro optical trap and demonstrate
      experimentally and theoretically the presence of both fast and slow relaxation
      processes, depending on the choice of the initial hyperfine states. This
      experimental method allows us to single out a particular relaxation process thus
      provides an extremely clean platform for collisional physics studies. Our results
      have also implications for engineering of quantum states via controlled
      collisions and creation of two-qubit quantum gates. 

PMID- 26199052
TI  - Proceedings of the ASNC cardiac PET summit meeting, May 12 2014, Baltimore MD :
      4. Novel applications of cardiovascular PET.
AB  - While it is well recognized that cardiac PET has the ability to accurately detect
      myocardial ischemia and coronary blood flow, there are multiple other novel and
      clinically important cardiac applications of PET which are now available for the
      evaluation of various disease processes of the cardiovascular system. Many of
      these applications utilize F18-fluorodeoxyglucose (FDG), a glucose analog which
      is retained within cells with a high metabolic activity and which has been used
      extensively in nuclear medicine to evaluate oncology patients and has recently
      also been used to evaluate infections. This review provides an overview of some
      of the clinically available novel applications, Figure 1, in cardiac PET which
      were discussed at the American Society of Nuclear Cardiology Cardiac PET Summit,
      May 12, 2014. Figure 1 Novel applications of cardiac PET.

PMID- 26199053
TI  - Evaluation on the Nanoscale Zero Valent Iron Based Microbial Denitrification for
      Nitrate Removal from Groundwater.
AB  - Nanoscale zero valent iron (NZVI) based microbial denitrification has been
      demonstrated to be a promising technology for nitrate removal from groundwater.
      In this work, a mathematical model is developed to evaluate the performance of
      this new technology and to provide insights into the chemical and microbial
      interactions in the system in terms of nitrate reduction, ammonium accumulation
      and hydrogen turnover. The developed model integrates NZVI-based abiotic
      reduction of nitrate, NZVI corrosion for hydrogen production and hydrogen-based
      microbial denitrification and satisfactorily describes all of the nitrate and
      ammonium dynamics from two systems with highly different conditions. The high
      NZVI corrosion rate revealed by the model indicates the high reaction rate of
      NZVI with water due to their large specific surface area and high surface
      reactivity, leading to an effective microbial nitrate reduction by utilizing the
      produced hydrogen. The simulation results further suggest a NZVI dosing strategy
      (3-6 mmol/L in temperature range of 30-40  degrees C, 6-10 mmol/L in temperature
      range of 15-30  degrees C and 10-14 mmol/L in temperature range of 5-15  degrees
      C) during groundwater remediation to make sure a low ammonium yield and a high
      nitrogen removal efficiency. 

PMID- 26199054
TI  - Institutional Racism as a Critical Social Determinant of Health.

PMID- 26199055
TI  - Measuring effectiveness.
AB  - Measuring the effectiveness of medical interventions faces three epistemological
      challenges: the choice of good measuring instruments, the use of appropriate
      analytic measures, and the use of a reliable method of extrapolating measures
      from an experimental context to a more general context. In practice each of these
      challenges contributes to overestimating the effectiveness of medical
      interventions. These challenges suggest the need for corrective normative
      principles. The instruments employed in clinical research should measure patient
      relevant and disease-specific parameters, and should not be sensitive to
      parameters that are only indirectly relevant. Effectiveness always should be
      measured and reported in absolute terms (using measures such as 'absolute risk
      reduction'), and only sometimes should effectiveness also be measured and
      reported in relative terms (using measures such as 'relative risk reduction')
      employment of relative measures promotes an informal fallacy akin to the base
      rate fallacy, which can be exploited to exaggerate claims of effectiveness.
      Finally, extrapolating from research settings to clinical settings should more
      rigorously take into account possible ways in which the intervention in question
      can fail to be effective in a target population. 

PMID- 26199056
TI  - Initial development of Prochilodus hartii (Pisces: Prochilodontidae) submitted to
      induced reproduction.
AB  - The Prochilodontidae prepare for reproduction in captivity, but neither ovulation
      nor spawning occurs, thus requiring induced reproduction for breeding and
      restocking. This study analyzed for the first time the embryogenesis and larval
      ontogeny of P. hartii submitted to induced reproduction by hypophysation with
      crude common carp pituitary extract. The extrusion of oocytes and sperm was
      performed manually and fertilization was done using the dry method. After
      fertilization, the eggs were kept in incubators at 23 degrees C. A
      stereomicroscope was used to measure egg diameter and to monitor embryo
      development. Samples of larvae were collected daily for 7 days for histological
      and biometric analyses. The recently extruded oocytes, non-hydrated, are
      spherical, grey, and non-adhesive with a diameter of 1480 +/- 39 MUm and after
      hydration, have a diameter of 2860 +/- 120 MUm. The positive response to
      hypophysation was 100% for females and 80% for males. Spawning occurred 7 h after
      the third hormonal dosage. The fertilization rate was 77% at 23 degrees C.
      Blastopore closure occurred at 6 h 45 min and embryonic development was completed
      36 h 10 min after fertilization. After 204 h post fertilization (hpf) the larvae
      reached a standard length of 6.56 +/- 0.14 mm with the yolk sac completely
      resorbed. In P. hartii, the oral cavity opening occurred 132 hpf. The results of
      this study provide knowledge to better understand induced reproduction, breeding,
      and management of P. hartii, a species with a high potential for pisciculture,
      and which is commercially important in the Jequitinhonha River basin. 

PMID- 26199057
TI  - Intramolecular Tsuji-Trost-type Allylation of Carboxylic Acids: Asymmetric
      Synthesis of Highly pi-Allyl Donative Lactones.
AB  - Tsuji-Trost-type asymmetric allylation of carboxylic acids has been realized by
      using a cationic CpRu complex with an axially chiral picolinic acid-type ligand
      (Cl-Naph-PyCOOH: naph = naphthyl, py = pyridine). The carboxylic acid and allylic
      alcohol intramolecularly condense by the liberation of water without
      stoichiometric activation of either nucleophile or electrophile part, thereby
      attaining high atom- and step-economy, and low E factor. This success can be
      ascribed to the higher reactivity of allylic alcohols as compared with the allyl
      ester products in soft Ru/hard Bronstead acid combined catalysis, which can
      function under slightly acidic conditions unlike the traditional Pd-catalyzed
      system. Detailed analysis of the stereochemical outcome of the reaction using an
      enantiomerically enriched D-labeled substrate provides an intriguing view of
      enantioselection. 

PMID- 26199059
TI  - Exploiting Non-Markovianity for Quantum Control.
AB  - Quantum technology, exploiting entanglement and the wave nature of matter, relies
      on the ability to accurately control quantum systems. Quantum control is often
      compromised by the interaction of the system with its environment since this
      causes loss of amplitude and phase. However, when the dynamics of the open
      quantum system is non-Markovian, amplitude and phase flow not only from the
      system into the environment but also back. Interaction with the environment is
      then not necessarily detrimental. We show that the back-flow of amplitude and
      phase can be exploited to carry out quantum control tasks that could not be
      realized if the system was isolated. The control is facilitated by a few strongly
      coupled, sufficiently isolated environmental modes. Our paradigmatic example
      considers a weakly anharmonic ladder with resonant amplitude control only,
      restricting realizable operations to SO(N). The coupling to the environment, when
      harnessed with optimization techniques, allows for full SU(N) controllability. 

PMID- 26199058
TI  - The role of decision-making in cannabis-related problems among young adults.
AB  - BACKGROUND: Deficits in decision-making and episodic memory are often reported
      among heavy cannabis users, yet little is known on how they influence negative
      consequences from cannabis use. Individual differences in decision-making may
      explain, in part, why some individuals experience significant problems from their
      cannabis use whereas others do not. We hypothesized that poor decision-making
      would moderate relationships between amount of cannabis use and problems from
      cannabis use whereas episodic memory performance would not. METHOD: Young adult
      cannabis users (n=52) with cannabis as their drug of choice and with minimal
      comorbidities completed semi-structured interviews, self-report questionnaires,
      and measures of neurocognitive functioning, with decision-making accessed via the
      Iowa Gambling Task (IGT), episodic memory via the Hopkins Verbal Learning Test -
      Revised (HVLT) and problems from cannabis use with the Marijuana Problems Scale.
      RESULTS: Strong relationships were observed between amount of cannabis use
      (lifetime, 12-month, and 30-day) and problems reported from use, but only among
      participants with low (impaired) decision-making (R(2)=.39 to .51; p<.01). No
      significant relationships were observed among those with better (low average to
      high average) decision-making performance (p>.05). In contrast, episodic memory
      performance was not a significant moderator of the relationship between amount of
      cannabis use and cannabis problems (p>.05). CONCLUSIONS: Cannabis users with poor
      decision-making may be at greater risk for experiencing significant negative
      consequences from their cannabis use. Our results lend further support to
      emerging evidence of decision-making as a risk factor for addiction and extend
      these findings to cannabis users.

PMID- 26199060
TI  - Hepatitis C virus and liver transplantation: where do we stand?
AB  - The hepatitis C virus (HCV) infects more than 180 million people globally, with
      increasing incidence, especially in developing countries. HCV infection
      frequently progresses to liver cirrhosis leading to liver transplantation or
      death, and HCV recurrence still constitutes a major challenge for the transplant
      team. Antiviral therapy is the only available instrument to slow down this
      process, although its actual impact on liver histology, in responders and
      nonresponders, is still controversial. We are now facing a "new era" of direct
      antiviral agents that is already changing the approach to HCV burden both in the
      pre- and in the post-liver transplantation settings. Available data on
      sofosbuvir/ledipasvir and sofosbuvir/simeprevir in patients with decompensated
      cirrhosis sustain a SVR12 of 89% , but one-third of patients do not clinically
      improved. The sofosbuvir/ribavirin treatment in stable cirrhotic patients with
      HCC before liver transplantation is associated with 2% recurrence rate if liver
      transplantation is performed at least one month after undetectable HCV-RNA is
      achieved. The treatment of recurrence with the new antiviral drugs is associated
      with a SVR that ranges between 60 and 90%. In this review, we have focused on the
      evolution of antiviral therapy for HCV recurrence from the "old" interferon-based
      therapy to the "new" interferon-free regimens, highlighting useful information to
      aid the transplant hepatologist in the clinical practice. 

PMID- 26199062
TI  - The in vitro protective effect of salicylic acid against paclitaxel and cisplatin
      induced neurotoxicity.
AB  - Paclitaxel (PAC) and cisplatin (CIS) are two established chemotherapeutic drugs
      used in combination for the treatment of various solid tumors. However, the usage
      of PAC and CIS are limited because of the incidence of their moderate or severe
      neurotoxic side effects. In this study, we aimed to assess the protective role of
      salicylic acid (SA) against neurotoxicity caused by PAC and CIS. For this
      purpose, newborn Sprague Dawley rats were decapitated in sterile atmosphere and
      primary cortex neuron cultures were established. On the 10th day SA was added
      into culture plates. PAC and CIS were added on the 12th day. The cytotoxicity was
      determined by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide] assay. Oxidative alterations were assessed using total antioxidant
      capacity and total oxidative stress assays in rat primary neuron cell cultures.
      It was shown that both concentrations of PAC and CIS treatments caused
      neurotoxicity. Although SA decreased the neurotoxicity by CIS and PAC, it was
      more effective against the toxicity caused by CIS rather than the toxicity caused
      by PAC. In conclusion it was clearly revealed that SA decreased the neurotoxic
      effect of CIS and PAC in vitro. 

PMID- 26199061
TI  - Rituximab-induced serum sickness: A systematic review.
AB  - OBJECTIVES: To report a case of rituximab-induced serum sickness (RISS) and
      perform a systematic review and characterize RISS in autoimmune diseases and
      hematological malignancies. METHODS: A comprehensive search of MEDLINE, EMBASE,
      ACR, and EULAR databases was performed for relevant articles of patients with
      RISS from inception to September 2014. Statistical analysis of demographic and
      clinical features was performed using Microsoft EXCEL 2007 and SPSS version 20.0.
      RESULTS: In the 33 patients with RISS, the mean age of presentation was 39.1 +/-
      17.5yr with a female preponderance (n = 23, 76.67%). The majority of cases were
      associated with an underlying rheumatologic condition (n = 17, 51.5%), most
      commonly Sjogren's syndrome (n = 8, 44.4%). The classic triad of serum sickness
      (fever, rash, and arthralgia) was reported in 16 (48.5%) cases. Time from drug
      exposure to symptom onset was significantly greater with the first doses of
      rituximab compared to the second dose (mean time 10.00 vs. 4.05d, P = 0.002), and
      time to resolution was significantly greater for rheumatologic vs. hematological
      indications (mean time 2.50 vs. 1.00d, P = 0.035). Corticosteroids were the most
      commonly used treatment (n = 21), with all cases reporting a complete resolution
      of symptoms in 2.15 +/- 1.34d. CONCLUSION: It is important to recognize RISS
      clinically, as it may mimic exacerbation of various rheumatologic conditions.
      Although RISS is typically self-limited, further infusions of rituximab should be
      avoided, as it may provoke more severe symptoms.

PMID- 26199063
TI  - Homeostasis of iron and hepcidin in erythropoietic protoporphyria.
AB  - BACKGROUND: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP)
      are genetic abnormalities of heme synthesis that result in excess production of
      protoporphyrin and that manifest as severe photosensitivity. These disorders are
      often associated with iron deficiency anaemia (IDA). Our aim was to determine
      whether hepcidin is increased in EPP/XLP patients, resulting in decreased enteral
      iron absorption and IDA. MATERIAL AND METHODS: Eight subjects with EPP, one with
      XLP and nine controls had baseline blood and urine samples collected, and
      thereafter were given oral ferrous sulphate (660 mg). Post-iron blood and urine
      samples were collected at 2, 4, 6 and 8 h. Blood counts, serum cytokines,
      ferritin and iron studies were analysed at baseline. Serum iron studies, serum
      and urine hepcidin, and erythropoietin (Epo) were analysed at baseline and
      subsequent time points. RESULTS: At baseline, EPP-XLP subjects had lower mean
      blood haemoglobin (13.9/15.3 g/dL) and serum ferritin (31.6/115 ng/mL) than
      controls. Serum iron levels increased markedly in both cohorts. Mean serum and
      urine hepcidin levels were significantly lower in the EPP-XLP group at 4 and 8 h
      post-iron (serum - 4 h, 3.79/26.6, 8 h, 5.79/34.6 nM; urine - 4 h, 0.85/2.50, 8
      h, 1.44/6.63 nM/mM creatinine). Serum cytokines and Epo were normal and not
      different between groups. CONCLUSIONS: We conclude that serum and urine hepcidin
      are not inappropriately increased in EPP/XLP subjects at baseline and do not
      increase over time as serum iron increases after oral ferrous sulphate. Levels of
      serum cytokines and Epo are normal in EPP/XLP. The molecular basis for the iron
      deficient phenotype in EPP/XLP remains unknown.

PMID- 26199065
TI  - Catch of the day: interventional device retrieval after late embolization of an
      Amplatzer cardiac plug left atrial appendage occluder.
AB  - Transcatheter left atrial appendage (LAA) closure has proven to be an effective
      method to reduce the risk of thromboembolic events in patients who have
      nonvalvular atrial fibrillation (AF) that is unsuitable for chronic oral
      anticoagulation. In this case report, we describe the rare case of a late LAA
      occluder (28-mm Amplatzer cardiac plug) embolization, which was treated
      uneventfully with interventional device capture. Special interventional and
      device specific characteristics must be taken into account when planning such a
      complex procedure as described in our case.

PMID- 26199064
TI  - Self-carried curcumin nanoparticles for in vitro and in vivo cancer therapy with
      real-time monitoring of drug release.
AB  - The use of different nanocarriers for delivering hydrophobic pharmaceutical
      agents to tumor sites has garnered major attention. Despite the merits of these
      nanocarriers, further studies are needed to improve their drug loading capacities
      (which are typically <10%) and reduce their potential systemic toxicity.
      Therefore, the development of alternative self-carried nanodrug delivery
      strategies without using inert carriers is highly desirable. In this study, we
      developed a self-carried curcumin (Cur) nanodrug for highly effective cancer
      therapy in vitro and in vivo with real-time monitoring of drug release. With a
      biocompatible C18PMH-PEG functionalization, the Cur nanoparticles (NPs) showed
      excellent dispersibility and outstanding stability in physiological environments
      with drug loading capacities >78 wt%. Both confocal microscopy and flow cytometry
      confirmed the cellular fluorescence "OFF-ON" activation and real-time monitoring
      of the Cur molecule release. In vitro and in vivo experiments clearly show that
      the therapeutic efficacy of the PEGylated Cur NPs is considerably better than
      that of free Cur. This self-carried strategy with real-time monitoring of drug
      release may open a new way for simultaneous cancer therapy and monitoring. 

PMID- 26199066
TI  - Experience matters: long-term results of pulmonary vein isolation using a robotic
      navigation system for the treatment of paroxysmal atrial fibrillation.
AB  - BACKGROUND: Long-term results after circumferential pulmonary vein isolation
      (CPVI) for the treatment of paroxysmal atrial fibrillation (PAF) using a robotic
      navigation system (RNS) have not yet been reported. OBJECTIVE: To evaluate long
      term results of patients with PAF after CPVI using RNS. METHODS: In this study,
      200 patients (n = 151 (75.5%) male; median age 62.2 (54.7-67.7) years) with PAF
      were evaluated. In 100 patients, RNS (RN-group) was used for CPVI and compared to
      100 manually ablated control patients (MN-group). Radiofrequency was used in
      conjunction with 3D electroanatomic mapping. Power was limited to 30 watts (W) at
      the posterior left atrial (LA) wall in the first 49 RNS patients (RN-group-a).
      After esophageal perforation occurred in one RN-group-a patient, maximum power
      was reduced to 20 W for the subsequent 51 patients (RN-group-b). RESULTS: After a
      median follow-up of 2 years, single (77/100 vs 77/100, p = 0.89) and multiple
      (90/100 vs 93/100, p = 0.29) procedure success rates were comparable between RN
      group and MN-group. Single procedure success rate was significantly lower in RN
      group-a as compared to RN-group-b (65.3 vs 88.2%, p = 0.047). In RN-group-a
      patients, procedural times [200 (170-230) vs 152 (132-200) minutes, p < 0.01] and
      fluoroscopy times [16.6 (12.9-21.6) minutes vs 13.7 (9.5-19) minutes, p = 0.043]
      were significantly longer compared to RN-group-b patients. CONCLUSION: Long-term
      success rate after CPVI using RNS was comparable to manual ablation. Despite a
      lower power limit of 20 W at the posterior LA wall, single procedure success rate
      was higher in RN-group-b as compared to RN-group-a. Procedure time and
      fluoroscopy time decreased, whilst success rate increased with increasing
      experience in the RN-group.

PMID- 26199067
TI  - Pre-administration of turmeric prevents methotrexate-induced liver toxicity and
      oxidative stress.
AB  - BACKGROUND: Methotrexate (MTX) is an antimetabolite broadly used in treatment of
      cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its
      application. We investigated hepatoprotective effects of turmeric in MTX-induced
      liver toxicity. METHODS: All experiments were performed on male Wistar albino
      rats that were randomly divided into six groups. Group one received saline orally
      for 30 days (control group), groups two and three received turmeric extract (100,
      200 mg/kg respectively) orally for 30 days, group four received single dose, of
      MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg
      orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at
      day 30. Four days after MTX injection animals were sacrificed and evaluated.
      Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers
      of biliary function), albumin (reflect liver synthetic function) as well as the
      plasma TAS concentration (antioxidant defenses) were determined. The cellular
      antioxidant defense activities were examined in liver tissue samples using SOD,
      CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In
      addition, liver damage was evaluated histopathologically. RESULTS: MTX
      significantly induced liver damage (P<0.05) and decreased its antioxidant
      capacity, while turmeric was hepatoprotective. Liver tissue microscopic
      evaluation showed that MTX treatment induced severe centrilobular and periportal
      degeneration, hyperemia of portal vein, increased artery inflammatory cells
      infiltration and necrosis, while all of histopathological changes were attenuated
      by turmeric (200 mg/kg). CONCLUSION: Turmeric extract can successfully attenuate
      MTX-hepatotoxicity. The effect is partly mediated through extract's
      antinflammatory activity.

PMID- 26199068
TI  - Exposure to family planning messages and modern contraceptive use among men in
      urban Kenya, Nigeria, and Senegal: a cross-sectional study.
AB  - BACKGROUND: Family planning (FP) researchers and policy makers have often
      overlooked the importance of involving men in couples' fertility choices and
      contraception, despite the fact that male involvement is a vital factor in sexual
      and reproductive health programming. This study aimed to assess whether men's
      exposure to FP demand-generation activities is associated with their reported use
      of modern contraceptive methods. METHODS: We used evaluation data from the
      Measurement, Learning & Evaluation project for the Urban Reproductive Health
      Initiative (URHI) in select cities of three African countries (Kenya, Nigeria,
      and Senegal) collected in 2012/2013. A two-stage cluster sampling design was used
      to select a representative sample of men in the study sites. The sample for this
      study includes men aged 15-59 years who had no missing data on any of the key
      variables: 696 men in Kenya, 2311 in Nigeria, and 1613 in Senegal. We conducted
      descriptive analyses and multivariate logistic regression analyses to assess the
      associations of interest. All analyses were weighted to account for the study
      design and non-response rates using Stata version 13. RESULTS: The proportion of
      men who reported use of modern contraceptive methods was 58 % in Kenya, 43 % in
      Nigeria, and 27 % in Senegal. About 80 % were exposed to at least one URHI demand
      generation activity in each country. Certain URHI demand-generation activities
      were significantly associated with men's reported use of modern contraception. In
      Kenya, those who participated in URHI-led community events had four times higher
      odds of reporting use of modern methods (aOR: 3.70; p < 0.05) while in Senegal,
      exposure to URHI-television programs (aOR: 1.40; p < 0.05) and having heard a
      religious leader speak favorably about FP (aOR: 1.72; p < 0.05) were associated
      with modern contraceptive method use. No such associations were observed in
      Nigeria. CONCLUSION: Study findings are important for informing future FP program
      activities that seek to engage men. Program activities should be tailored by
      geographic context as results from this study indicate city and country-level
      variations. These types of gender-comprehensive and context-specific programs are
      likely to be the most successful at reducing unmet need for FP.

PMID- 26199071
TI  - Household bush burning practice and related respiratory symptoms in Grenada, the
      Caribbean.
AB  - The practice of household bush burning in Grenada occurs frequently, though it is
      not well documented. The effects of the emissions from bush burning on
      respiratory health of the population have never been researched in Grenada. The
      goal of the study was to measure the frequency of bush burning and to investigate
      the relationship between bush burning practice and respiratory health in Grenada.
      In this cross-sectional study, a questionnaire was used to gather information
      from households in the parishes of St. George and St. Andrew, Grenada. In total,
      225 participants were recruited and their responses on household bush burning and
      respiratory symptoms were analyzed. Self-reported data showed that the practice
      of bush burning was conducted by 43% (n = 96) of the participants as a regular
      practice (every month) and 86% (n = 192) of participants stated that their
      neighbors burn bush regularly. The most common lower respiratory symptom
      associated with bush burning was dry cough (31.4%). The participants who engage
      in the practice of bush burning had a statistically significant, higher
      prevalence of sinusitis symptoms (OR: 2.1, CI 95%: 1.1-3.9) and had slightly
      higher prevalence of cough (OR: 1.6, CI 95%: 0.9-2.8). Prevalences of physician
      diagnosed asthma and sinusitis were 12.3% and 31.2%, respectively. Conducting
      studies on the health effects of bush burning in different settings and with
      different practices, such as the household bush burning in our current study,
      could help to improve public health in the developing world. IMPLICATIONS:
      Household disposal of waste is a significant issue in the developing world. In
      particular, residential bush burning is a common practice in tropical regions.
      This study demonstrates that the common practice of bush burning in the Caribbean
      is associated with respiratory symptoms and demonstrates the need for better
      management of residential yard waste. Burning of yard waste results in
      potentially significant exposures to air pollution and therefore alternative
      disposal practices need to be available. There is a need to increase awareness of
      the importance of avoiding exposure to the air pollutants generated during bush
      burning among communities in the Caribbean.

PMID- 26199070
TI  - Consumption of sugar sweetened beverages, artificially sweetened beverages, and
      fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis,
      and estimation of population attributable fraction.
AB  - OBJECTIVES: To examine the prospective associations between consumption of sugar
      sweetened beverages, artificially sweetened beverages, and fruit juice with type
      2 diabetes before and after adjustment for adiposity, and to estimate the
      population attributable fraction for type 2 diabetes from consumption of sugar
      sweetened beverages in the United States and United Kingdom. DESIGN: Systematic
      review and meta-analysis. DATA SOURCES AND ELIGIBILITY: PubMed, Embase, Ovid, and
      Web of Knowledge for prospective studies of adults without diabetes, published
      until February 2014. The population attributable fraction was estimated in
      national surveys in the USA, 2009-10 (n = 4729 representing 189.1 million adults
      without diabetes) and the UK, 2008-12 (n = 1932 representing 44.7 million).
      SYNTHESIS METHODS: Random effects meta-analysis and survey analysis for
      population attributable fraction associated with consumption of sugar sweetened
      beverages. RESULTS: Prespecified information was extracted from 17 cohorts
      (38,253 cases/10,126,754 person years). Higher consumption of sugar sweetened
      beverages was associated with a greater incidence of type 2 diabetes, by 18% per
      one serving/day (95% confidence interval 9% to 28%, I(2) for heterogeneity = 89%)
      and 13% (6% to 21%, I(2) = 79%) before and after adjustment for adiposity; for
      artificially sweetened beverages, 25% (18% to 33%, I(2) = 70%) and 8% (2% to 15%,
      I(2) = 64%); and for fruit juice, 5% (-1% to 11%, I(2) = 58%) and 7% (1% to 14%,
      I(2) = 51%). Potential sources of heterogeneity or bias were not evident for
      sugar sweetened beverages. For artificially sweetened beverages, publication bias
      and residual confounding were indicated. For fruit juice the finding was non
      significant in studies ascertaining type 2 diabetes objectively (P for
      heterogeneity = 0.008). Under specified assumptions for population attributable
      fraction, of 20.9 million events of type 2 diabetes predicted to occur over 10
      years in the USA (absolute event rate 11.0%), 1.8 million would be attributable
      to consumption of sugar sweetened beverages (population attributable fraction
      8.7%, 95% confidence interval 3.9% to 12.9%); and of 2.6 million events in the UK
      (absolute event rate 5.8%), 79,000 would be attributable to consumption of sugar
      sweetened beverages (population attributable fraction 3.6%, 1.7% to 5.6%).
      CONCLUSIONS: Habitual consumption of sugar sweetened beverages was associated
      with a greater incidence of type 2 diabetes, independently of adiposity. Although
      artificially sweetened beverages and fruit juice also showed positive
      associations with incidence of type 2 diabetes, the findings were likely to
      involve bias. None the less, both artificially sweetened beverages and fruit
      juice were unlikely to be healthy alternatives to sugar sweetened beverages for
      the prevention of type 2 diabetes. Under assumption of causality, consumption of
      sugar sweetened beverages over years may be related to a substantial number of
      cases of new onset diabetes.

PMID- 26199072
TI  - Prognostic robustness of serum creatinine based AKI definitions in patients with
      sepsis: a prospective cohort study.
AB  - BACKGROUND: It is unclear how modifications in the way to calculate serum
      creatinine (sCr) increase and in the cut-off value applied, influences the
      prognostic value of Acute Kidney Injury (AKI). We wanted to evaluate whether
      these modifications alter the prognostic value of AKI for prediction of mortality
      at 3 months, 1 and 2 years. METHODS: We prospectively included 195 septic
      patients and evaluated the prognostic value of AKI by using three different
      algorithms to calculate sCr increase: either as the difference between the
      highest value in the first 24 h after ICU admission and a pre-admission
      historical (DeltaHIS) or an estimated (DeltaEST) baseline value, or by
      subtracting the ICU admission value from the sCr value 24 h after ICU admission
      (DeltaADM). Different cut-off levels of sCr increase (0.1, 0.2, 0.3, 0.4 and 0.5
      mg/dl) were evaluated. RESULTS: Mortality at 3 months, 1 and 2 years in AKI
      defined as DeltaADM > 0.3 mg/dl was 48.1 %, 63.0 % and 63.0 % vs 27.7 %, 39.8 %
      and 47.6 % in no AKI respectively (OR(95%CI): 2.42(1.06-5.54), 2.58(1.11-5.97)
      and 1.87(0.81-4.33); 0.3 mg/dl was the lowest cut-off value that was
      discriminatory. When AKI was defined as DeltaHIS > 0.3 mg/dl or DeltaEST > 0.3
      mg/dl, there was no significant difference in mortality between AKI and no AKI.
      CONCLUSIONS: The prognostic value of a 0.3 mg/dl increase in sCr, on mortality in
      sepsis, depends on how this sCr increase is calculated. Only if the evolution of
      serum creatinine over the first 24 h after ICU admission is taken into account,
      an association with mortality is found.

PMID- 26199073
TI  - Magneto-structural variety of new 3d-4f-4(5)d heterotrimetallic complexes.
AB  - Three families of heterotrimetallic chains (type 1-type 3), with different
      topologies, have been obtained by reacting the 3d-4f complexes,
      [{Cu(L(1))}xLn(NO3)3] with x = 1 or 2, formed in situ by the reaction of Schiff
      base bi-compartmental [Cu(II)(L(1))] complexes and lanthanide(iii) salts, with
      (NHBu3)3[M(CN)8] (M = Mo(V), W(V)). For type 1 series of compounds, 1-D
      coordination polymers, with the general formula
      [{Cu2(valpn)2Ln}{M(CN)8}].nH2O.mCH3CN (where H2valpn = 1,3-propanediylbis(2
      iminomethylene-6-methoxy-phenol), result from the association of trinuclear
      {CuLn(III)} moieties and [M(V)(CN)8](3-) anions acting as tri-connecting spacers
      [Ln = La (1), Ce (2), Eu (3), Tb (4), Ho (5), M = Mo; Ln = Tb (6), Ho (7), M = W;
      m = 0, n = 1.5 (7) and 2 (1-4, 6); n = 1, m = 1 (5)]. The type 2 family has the
      general formula [{Cu(valdp)Ln(H2O)4}{M(CN)8}].2H2O.CH3CN (where H2valdp = 1,2
      propanediylbis(2-iminomethylene-6-methoxy-phenol)) and also consists of
      heterotrimetallic chains involving binuclear {Cu(II)Ln(III)} units linked to
      [M(CN)8](3-) anions coordinating through two cyano groups [Ln = Gd (8), Tb (9),
      Dy (10); M = Mo; Ln = La (11), Gd (12), Tb (13), Dy (14); M = W]. With large
      Ln(III) ions (La(III) and Pr(III)), the type 3 family of heterotrimetallic
      compounds are assembled: [{Cu2(valdp)2Ln(H2O)4}{Mo(CN)8}].nCH3OH.mCH3CN, n, m =
      0, Ln = La (15); n = m = 1, Pr (16), in which the trinuclear {CuLn(III)} nodes
      are connected to [Mo(V)(CN)8](3-) anions that act as tetra-connecting spacers.
      For Tb(III) derivatives of the type 1 (compounds 4 and 6), the DC magnetic
      properties indicate a predominant ferromagnetic Cu(II)-Tb(III) interaction, while
      the AC magnetic susceptibility (in the presence of a static magnetic field, HDC =
      3000 Oe) emphasize the slow relaxation of the magnetization (Ueff/kB = 20.55 K
      and tau0 = 5.5 * 10(-7) s for compound 4, Ueff/kBT = 15.1 K and tau0 = 1.5 * 10(
      7) s for compound 6). A predominant ferromagnetic Cu(II)-Ln(III) interaction was
      also observed in the type 2 series (compounds 8-10 and 12-14) as a result of the
      magnetic coupling between copper(ii) and lanthanide(iii) ions via the phenoxo
      bridge. The magnetic behavior for the La(III) derivatives reveals that weak
      ferromagnetic interactions are also operative between the Cu(II) and the 4d/5d
      centers. 

PMID- 26199074
TI  - Traumatic bilateral carotid artery dissection following severe blunt trauma: a
      case report on the difficulties in diagnosis and therapy of an often overlooked
      life-threatening injury.
AB  - BACKGROUND: Traumatic carotid artery dissections are very rare, often overlooked
      and life-threatening injuries. Diagnosis and treatment are difficult especially
      in multiple injured patients. CASE PRESENTATION: We report on a 28-year-old
      female major trauma patient (injury severity score, ISS 50) who was involved in a
      motor vehicle accident. She was primarily transferred to a level II trauma
      center. After initial assessment and operative management, an anisocoria was
      diagnosed on the intensive care unit. Subsequent CT angiography and extracranial
      duplex sonography revealed a bilateral internal carotid artery dissection. The
      patient was transferred to our level I trauma center where conservative treatment
      with high-dose heparin therapy was started at day two after trauma. Outcome after
      6 months was very good. CONCLUSION: Besides presenting the case and outcome of
      this patient, the article discusses the diagnostic and therapeutic management of
      this extremely rare and often overlooked dangerous injury. To avoid overlooking
      carotid artery dissections, CT angiography of the neck region should be
      generously included into the initial multislice CT whole-body scan, when the
      injury results from an according trauma. For the best outcome, sites of
      hemorrhage should be abolished quickly and the anticoagulative therapy should be
      initiated as soon as possible. Interdisciplinary treatment of trauma surgeons and
      neurologists is crucial.

PMID- 26199075
TI  - Pulmonary Manifestations of Neuromuscular Diseases.
AB  - Neuromuscular disorders comprise a phenotypically diverse group of inherited and
      acquired diseases; however, they share common pathophysiologic mechanisms which
      produce significant respiratory complications. Respiratory and bulbar muscle
      weakness gives rise to ineffective cough, swallowing dysfunction results in
      aspiration-related lung disease, and abnormal muscle tone produces chest wall
      deformities - all of which ultimately leads to repeated chest infections and
      chronic respiratory failure. In this article, the authors describe the
      respiratory manifestations of neuromuscular disease and their underlying
      pathophysiological mechanisms. This review also highlights the diagnostic and
      management tools recommended for acute and chronic care. Aggressive pulmonary
      management is the most impactful at reducing the overall morbidity and improving
      the quality of life of children with neuromuscular disorders, at least while
      definitive molecular and gene replacement therapies remain elusive.

PMID- 26199077
TI  - Acute Hemorrhagic Leucoencephalitis.

PMID- 26199076
TI  - Moving from Survival to Healthy Survival through Child Health Screening and Early
      Intervention Services Under Rashtriya Bal Swasthya Karyakram (RBSK).
AB  - For negating the impact of early adversities on the development and ensuring a
      healthy, dynamic future for all children, Ministry of Health and Family Welfare
      in 2013 launched a programme for child health screening and early intervention
      services as Rashtriya Bal Swasthya Karyakram (RBSK) which aims to improve the
      quality of life with special focus on improving cognition and survival outcomes
      for "at risk" children. It has a systemic approach of prevention, early
      identification and management of 30 health conditions distributed under 4Ds:
      Defects at birth, Diseases, Deficiencies and Developmental delays including
      Disabilities spread over birth to 18 y of age in a holistic manner. There is a
      dedicated 4 member Mobile Health team for community screening and a dedicated 14
      member team at District Early Intervention Center (DEIC) for comprehensive
      management. Existing health infrastructure and personnel are also integrated and
      utilized in this endeavor. Defects at birth are screened at Delivery points, home
      visits by accredited social health activist (ASHA), Anganwadi centers and at
      schools. Developmental delays are evaluated at DEIC through a multidisciplinary
      team with interdisciplinary approach. Five thousand four hundred eighteen
      dedicated Mobile Health teams have screened a total of 12.19 crore children till
      Dec.14. From April to Dec. 2014, 4.20 crore children were screened, of which
      birth to 6-y-old children were 2.13 crore while 2.07 crore were from 6 to 18 y.
      17.7 lakh children were referred to tertiary centers and 6.2 lakh availed
      tertiary care. 50.7 lakhs were found positive for 4Ds; 1.35 lakhs were birth
      defects. RBSK is a step towards universal health care for free assured services. 

PMID- 26199078
TI  - Does College Matter for Emerging Adulthood? Comparing Developmental Trajectories
      of Educational Groups.
AB  - Critics of emerging adulthood theory have suggested that it only applies to
      college students, but this assertion has largely gone untested. The purpose of
      the present study was to compare developmental trajectories of non-students
      versus college-educated youth in theoretically relevant domains of work, love,
      and financial independence. Using data from the Youth Development Study (N =
      1139, 49.6 % female, 63.3 % White, 10.9 % Southeast Asian, 1.5 % Other Asian, 8.6
      % Black, 5.3 % Mixed Race, 4.0 % Latino, 0.8 % Native American), latent growth
      curve models were fitted to chart each group's development, from ages 14 to 30.
      Different trajectories were revealed for hours worked, children, and financial
      dependence on parents, spouses, and government aid. No differences were found in
      employment rates, marriage rates, or financial dependence on own income. These
      results provide a clearer picture of emerging adulthood for non-students, and
      highlight problems with generalizing college student research to all emerging
      adults. 

PMID- 26199079
TI  - The Relationship Between Autonomy and Relatedness and Adolescents' Adrenocortical
      and Cardiovascular Stress Response.
AB  - Developing autonomy and maintaining relatedness within the parent-adolescent
      relationship marks a realignment process that shifts adolescents' decision making
      and regulation from parents to youth. This process may be stressful for some
      adolescents, particularly those who perceive their daily lives as stressful. This
      study examined the associations of autonomy, relatedness and perceived stress
      with adolescents' cortisol and blood pressure response to conflict in a mother
      adolescent interaction task among 100 adolescents (M age = 15.09; 68 % girls, 78
      % Caucasian). Few direct associations were found, but results indicated that
      perceived stress moderated the effect of autonomy and relatedness such that youth
      who reported more perceived stress and whose mothers' restricted their autonomy
      and undermined their relatedness evidenced increased cortisol and systolic blood
      pressure when compared to youth lower in perceived stress. The results highlight
      the importance of examining individual differences in the association between
      normative developmental transitions and adolescents' neurobiological response to
      stress. 

PMID- 26199080
TI  - Regulation of T cell function by microRNA-720.
AB  - Chronic hepatitis B virus (HBV) infection is a major global health burden.
      Functional exhaustion and numerical reduction of HBV-specific cytotoxic T
      lymphocytes (CTLs) in the liver and peripheral blood limit anti-HBV CTL activity
      in patients with chronic HBV infection (CHB). However, the ongoing anti-HBV
      CD8(+) T cell responses in the lymphoid organs are largely unknown due to the
      infeasibility of obtaining lymphoid organs from CHB patients. Here we demonstrate
      that the percentage of HBV-specific CD8(+) T cells is higher in the spleen of CHB
      patients than that from peripheral blood and liver. Although they do respond to
      TCR stimulation and produce IFNgamma, the cells proliferate poorly. Furthermore,
      miR-720 expression is upregulated in HBV-specific CD8(+) T cells. Overexpression
      of miR-720 in primary human CD8(+) T cells inhibits TCR stimulation-induced
      proliferation. We also demonstrate that TGFbeta sustains miR-720 upregulation
      after TCR stimulation, and blood TGFbeta levels are associated with the outcome
      of type I interferon treatment of CHB patients. Thus, therapies targeting miR-720
      may help restore impaired immunity in CHB patients. 

PMID- 26199082
TI  - Short-term outcome of very-low-birthweight infants with arterial hypotension in
      the first 24 h of life.
AB  - OBJECTIVE: To evaluate lowest mean arterial blood pressure during the first 24 h
      of life (minMAP(24)) in very-low-birthweight (VLBW) infants and to identify
      associations between hypotension and short-term outcome. DESIGN: Retrospective
      cohort analysis of the minMAP(24) of 4907 VLBW infants with a gestational age <32
      weeks in correlation with clinical data. Hypotension was defined as minMAP(24)
      being lower than the median value of all patients of the same gestational age.
      RESULTS: MinMAP(24) values correlated with gestational age. Median minMAP(24)
      values of VLBW infants <=29 weeks' gestation were 1-2 mm Hg lower than
      gestational age in completed weeks. Hypotensive infants had a higher rate of
      intraventricular haemorrhage (IVH, 20.3% vs 15.9%, p<0.001), bronchopulmonary
      dysplasia (BPD, 19.2% vs 15.1%, p<0.001) and death (5.2% vs 3.0%, p<0.001).
      Multivariate logistic regression analyses, including potential confounders,
      confirmed these data. MinMAP(24) was an independent risk factor for IVH (OR
      0.97/mm Hg, 95% CI 0.96 to 0.99, p=0.003), BPD (OR 0.96/mm Hg, 95% CI 0.94 to
      0.98, p<0.001) and mortality (OR 0.94/mm Hg, 95% CI 0.90 to 0.98, p=0.003).
      CONCLUSIONS: Hypotension during the first 24 h of life is associated with adverse
      outcomes in VLBW infants. This underlines the need for randomised controlled
      trials on the use of vasoactive drugs in this vulnerable patient cohort.

PMID- 26199083
TI  - Decreased neural activity and neural connectivity while performing a set-shifting
      task after inhibiting repetitive transcranial magnetic stimulation on the left
      dorsal prefrontal cortex.
AB  - BACKGROUND: Sub-optimal functioning of the dorsal prefrontal cortex (PFC) is
      associated with executive dysfunction, such as set-shifting deficits, in
      neurological and psychiatric disorders. We tested this hypothesis by
      investigating the effect of low-frequency 'inhibiting' off-line repetitive
      transcranial magnetic stimulation (rTMS) on the left dorsal prefrontal cortex on
      behavioural performance, neural activity, and network connectivity during the
      performance of a set-shifting paradigm in healthy elderly (mean age 50+).
      RESULTS: Behaviorally, we found a group-by-session interaction for errors on set
      shift trials, although post hoc tests did not yield significant findings. In
      addition, the verum group, when compared with the sham group, displayed reduced
      task-related activity in the left temporal gyrus, and reduced task-related
      connectivity of the left PFC with the left postcentral gyrus and posterior
      insula. CONCLUSION: These results show that low-frequency off-line rTMS on the
      left dorsal PFC resulted in reduced task-related activity and network
      connectivity, which was accompanied by a subtle behavioural effect, thereby
      further corroborating the importance of an optimally functioning PFC in set
      shifting.

PMID- 26199084
TI  - Potential protective effects of l-carnitine against neuromuscular ischemia
      reperfusion injury: From experimental data to potential clinical applications.
AB  - BACKGROUND & AIM: Ischemia-reperfusion (I/R) injury plays important role in
      morbidity and mortality in several pathologies, including myocardial infarction,
      ischemic stroke, acute kidney injury, trauma, and circulatory arrest. An
      imbalance in metabolic supply and tissue's demand during ischemia results in
      profound tissue hypoxia and microvascular dysfunction. Subsequently, reperfusion
      further results in activation of immune responses and cell death programs. l
      carnitine and its derivatives have been administered to improve tolerance against
      I/R injury in various tissues. Anti-ischemic properties of l-carnitine and its
      derivative in neuromuscular organs will be reviewed here at the light of
      pertinent results from basic and clinical researches. METHOD: All available in
      vitro and in vivo studies, patents, clinical trials, and meeting abstracts in
      English language that examined the protective effects of l-carnitine against I/R
      induced injury in neuromuscular organs were reviewed. Materials were obtained by
      searching ELSEVIER, web of knowledge, PubMed, Scopus, clinical trials, and
      Cochrane database of systematic reviews. CONCLUSION: Although animal studies on
      central nervous system and some human studies on muscular system were in favors
      of effects of l-carnitine against I/R injury, however, more clinical trials are
      needed to clarify the clinical importance of l-carnitine as a treatment option to
      manage I/R-induced injury of neuromuscular system.

PMID- 26199085
TI  - Effect of specific educational program on dietary change and weight loss in
      breast-cancer survivors.
AB  - AIMS: Consumption of Western foods with high dietary glycemic load is associated
      with breast cancer development, whereas adherence to Mediterranean diet has been
      linked to a reduced risk. Changing lifestyle can decrease risk of recurrences and
      mortality. Thus decreasing the weight, improving the diet and promoting lifestyle
      are among of the most important issues of public health. We evaluated the effects
      of a specific educational intervention conducted by dietitians, nutritionists
      physicians, oncologist and sport physician to promote lifestyle in breast cancer
      survivors. METHODS: We recruited 100 pts in breast cancer follow up. The
      intervention program consisted of four meetings once a week including lectures,
      training sessions and workshops lasting overall a month. Dietary recommendations
      were provided on the basis of WCRF/AICR guidelines and were modelled on
      Mediterranean diet. Sport physician recommended adapted physical activity, based
      on clinical experiences and scientific evidences. RESULTS: Significantly decrease
      of BMI and waist circumference was observed after 2 and 6 months. Adherence to
      Mediterranean diet was significantly improved, both in heightening typical
      Mediterranean foods, both in decreasing consumption of non typical foods. At
      baseline 63% of women was inactive, 37% was mild active and 0% active, while at
      the end inactive patients felt by half (30%) and mild active women almost doubled
      (67%). CONCLUSIONS: We found this dietary intervention effective in reducing BMI
      and waist circumference, and enhancing healthy lifestyle in BC survivors. It has
      surely contributed to achieve these results besides the change in diet quality,
      mostly a marked reduction in sedentary habits.

PMID- 26199086
TI  - Current therapeutic strategies for rectal cancer.

PMID- 26199087
TI  - Gender and the double burden of economic and social disadvantages on healthy
      eating: cross-sectional study of older adults in the EPIC-Norfolk cohort.
AB  - BACKGROUND: Multiple economic factors and social relationships determine dietary
      behaviours, but the inter-relations between determinants is unknown. Whether
      women and men differ in the vulnerability to, and impact of, combined
      disadvantages is also unclear. We examined associations between diverse
      combinations of economic resources and social relationships, and healthy eating
      in British older women and men. METHODS: Our sample comprised 9,580 over-50s (47
      % of over-50 respondents) in the EPIC-Norfolk cohort study. We examined six
      economic factors (education, social class, home-ownership, money for needs,
      frequency of insufficient money for food/clothing, paying bills) and three social
      relationships (marital status, living arrangement and friend contact),
      independently and in combination, in relation to fruit variety and vegetable
      variety. We analysed gender-specific associations using multivariable linear
      regression with interaction terms. RESULTS: Lower social class, lower education,
      and difficulty paying bills were associated with lower fruit and vegetable
      variety in both genders, independent of social relationships. All social
      relationships were independently associated with fruit variety in men and with
      vegetable variety in both genders. Substantially lower variety was found for all
      combinations of low economic resources and lack of social relationship than for
      either measure alone, with men faring worse in the majority of combined
      disadvantages. For example, the difference in vegetable variety for men reporting
      low social class and non-married was much greater (beta -4.1, [-4.8, -3.4]), than
      the independent association of low social class (beta -1.5, [-1.8,-1.2]), or non
      married (beta -1.8, [-2.3,-1.3]). Variety was also lower among men with high
      economic resources but non-married or lone-living. CONCLUSION: A double burden of
      low economic resources and lack of social relationships suggested they are unique
      joint determinants, particularly in older men, and that public health efforts to
      improve healthy eating would offer most benefit to older adults with intersecting
      economic and social disadvantages.

PMID- 26199088
TI  - Transfer-messenger RNA and SmpB mediate bacteriostasis in Escherichia coli cells
      against tRNA cleavage.
AB  - RNAs, such as mRNA, rRNA and tRNA, are essential macromolecules for cell survival
      and maintenance. Any perturbation of these molecules, such as by degradation or
      mutation, can be toxic to cells and may occasionally induce cell death.
      Therefore, cells have mechanisms known as quality control systems to eliminate
      abnormal RNAs. Although tRNA is a stable molecule, the anticodon loop is quite
      susceptible to tRNA-targeting RNases such as colicin E5 and colicin D. However,
      the mechanism underlying cellular reaction to tRNA cleavage remains unclear. It
      had long been believed that tRNA cleavage by colicins E5 and D promptly induces
      cell death because colony formation of the sensitive cells is severely reduced;
      this indicates that cells do not resist the tRNA cleavage. Here, we show that
      Escherichia coli cells enter a bacteriostatic state against the tRNA cleavage of
      colicins D and E5. The bacteriostasis requires small protein B (SmpB) and
      transfer-messenger RNA (tmRNA), which are known to mediate trans-translation.
      Furthermore, another type of colicin, colicin E3 cleaving rRNA, immediately
      reduces the viability of sensitive cells. Moreover, nascent peptide degradation
      has an additive effect on bacteriostasis. Considering the recent observation that
      tRNA cleavage may be used as a means of cell-to-cell communication, tRNA cleavage
      could be used by bacteria not only to dominate other bacteria living in the same
      niche, but also to regulate growth of their own or other cells.

PMID- 26199089
TI  - Pap smear in the prevention of HPV-related anal cancer: preliminary results of
      the study in a male population at risk.
AB  - BACKGROUND: The aim of this work was to evaluate the role of human papillomavirus
      (HPV) testing and anal cytology, considering a population of HIV-positive and
      negative men who have sex with men (MSM), at high risk of sexually transmitted
      diseases (STD), in order to ascertain which of the methods examined is the best
      screening strategy for the prevention of anal cancer. METHODS: In the period
      06/2013-07/2014 at the "MTS Centre" of the University of Florence, 87 male
      patients, homo/bi-sexual, of which 46 HIV-negative and 41 HIV-positive, were
      recruited for anal Pap smear and HPV testing. All patients with an "abnormal"
      cytological result underwent anoscopy with possible biopsy. RESULTS: HPV testing
      was positive in 73 patients (83.6%). Cytology was negative in 50 patients
      (57.5%), inconclusive in 14 patients (16.1%), abnormal in 23 patients (26.4%): 14
      ASC-US (19.2%), 4 ASC-H (5.5%), 5 L-SIL (6.8%), 0 H-SIL. Anoscopy with biopsy led
      to diagnosis of AIN I in 10 cases, of which 6 ASC-US+ and 4L-SIL+, AIN II in only
      1 case, LS-IL+. CONCLUSIONS: Anal HPV testing, when used in primary screening,
      lead to a high number of "false positives", given the too high prevalence of HPV
      infection in MSM, the highest risk population targeted for screening. So we
      propose a screening program with anal cytology which has a high sensitivity for
      detection of AIN while is a poor predictor of the severity of these lesions;
      therefore, all patients with abnormal anal Pap smear should undergo anoscopy with
      biopsy.

PMID- 26199090
TI  - Psoriasis in elderly and non-elderly population: clinical and molecular features.
AB  - BACKGROUND: Psoriasis management in elderly may be difficult, mainly due to
      comorbidities and concomitant medications. The aim of this study was to compare
      elderly and non-elderly psoriatic patients in relation to their demographic,
      clinical and molecular characteristics. METHODS: A prospective observational
      study on 502 psoriatic patients attending our outpatient clinic was performed. We
      analyzed their demographical and clinical features, highlighting differences in
      comorbidities and treatment adverse events. Moreover, real-time PCR was used to
      analyze lesional skin expression of CCL-20, HBD-2, Hpt, IFN-alpha, IL-1beta, IL
      8, IL-23A, IL-33, IL-36gamma, TGF-beta, TNF-alpha, S100A7 and VEGF, in 15 adults
      and 15 elderly. RESULTS: The two groups of patients differed for comorbidities
      and treatment profile. Particularly, non-elderly were treated more frequently
      with biologic drugs compared to elderly. However, elderly did not develop more
      metabolic, hepatic and/or renal abnormalities than younger patients. Serious
      adverse events were comparable between elderly and non-elderly. No difference in
      gene expression of the investigated mediators was found. CONCLUSIONS: Our study
      did not show substantial clinical or molecular differences between elderly and
      non-elderly. Older patients should be treated with systemic drugs when required.
      Safety and tolerability profiles of biological drugs seemed at least comparable
      with those of traditional systemic ones.

PMID- 26199091
TI  - ABCG2 Transporter Expression Impacts Group 3 Medulloblastoma Response to
      Chemotherapy.
AB  - While a small number of plasma membrane ABC transporters can export
      chemotherapeutic drugs and confer drug resistance, it is unknown whether these
      transporters are expressed or functional in less therapeutically tractable
      cancers such as Group 3 (G3) medulloblastoma. Herein we show that among this
      class of drug transporters, only ABCG2 was expressed at highly increased levels
      in human G3 medulloblastoma and a mouse model of this disease. In the mouse
      model, Abcg2 protein was expressed at the plasma membrane where it functioned as
      expected on the basis of export of prototypical substrates. By screening ABC
      substrates against mouse G3 medulloblastoma tumorspheres in vitro, we found that
      Abcg2 inhibition could potentiate responses to the clinically used drug
      topotecan, producing a more than 9-fold suppression of cell proliferation.
      Extended studies in vivo in this model confirmed that Abcg2 inhibition was
      sufficient to enhance antiproliferative responses to topotecan, producing a
      significant survival advantage compared with subjects treated with topotecan
      alone. Our findings offer a preclinical proof of concept for blockade of ABCG2
      transporter activity as a strategy to empower chemotherapeutic responses in G3
      medulloblastoma.

PMID- 26199092
TI  - Loss of RACK1 Promotes Metastasis of Gastric Cancer by Inducing a miR-302c/IL8
      Signaling Loop.
AB  - Gastric cancer remains the third leading cause of cancer-related mortality
      worldwide, and invasion and metastasis of gastric cancer represent the major
      reason for its poor prognosis. In this study, we found that loss of the receptor
      for activated C-kinase 1 (RACK1) promoted the metastasis of gastric cancer by
      enhancing the autocrine expression of IL8 in vitro and in vivo. microRNA (miRNA;
      miR) array identified that RACK1 modulated the expression of a series of miRNAs,
      including the miR-302 cluster, and RACK1 modulated the IL8 expression and tumor
      invasion through miRNA-302c. Moreover, upregulation of IL8 in turn decreased the
      level of miRNA-302c and induced IL8 expression in a feedback manner. Tissue
      microarray also indicated that RACK1 was correlated with invasion/metastasis
      phenotype, IL8 expression, as well as 5-year survival in clinical cases of
      gastric cancer. Together, our results imply that loss of RACK1 in gastric cancer
      links epigenetics to inflammatory cytokines to promote tumor metastasis.

PMID- 26199093
TI  - Melatonin: a potential intervention for hepatic steatosis.
AB  - Melatonin (N-acetyl-5-methoxytryptamine, MLT) is a neuroendocrine hormone, which
      is primarily synthesized by the pineal gland in vertebrates. Melatonin is a
      remarkable molecule with diverse biological and physiological actions and is
      involved in the regulation of various important functions such as circadian
      rhythm, energy metabolism, the reproductive system, the cardiovascular system,
      and the neuropsychiatric system. It also plays a role in disease by having anti
      neoplastic and anti-osteoarthritic effects among others. Recently, research has
      focused on the roles of melatonin in oxidative stress, lipid metabolism, and
      hepatic steatosis and its potential therapeutic roles. 

PMID- 26199094
TI  - The role of the metastasis suppressor gene KAI1 in melanoma angiogenesis.
AB  - The tetraspan protein KAI1 (CD82) has been previously shown to have important
      roles in cell migration, invasion, and melanoma prognosis. In this study, we
      investigated the role of KAI1 regarding melanoma angiogenesis. KAI1
      overexpression strongly suppressed the growth of the human umbilical vein
      endothelial cells and their tubular structure formation in vitro. Also, KAI1 was
      able to inhibit both interleukin-6 (IL-6) and VEGF at mRNA and protein levels.
      Using nude mice in the in vivo study, we showed that KAI1, through the regulation
      of ING4, inhibited blood vessel formation in matrigel plugs along with the
      downregulation of IL-6 and VEGF, and the recruitment of CD31-positive cells.
      Finally, we found that KAI1 was able to suppress the activity of a
      serine/threonine kinase Akt by suppressing Akt phosphorylation (Ser473). Taken
      together, our results suggested that KAI1 was able to suppress melanoma
      angiogenesis by downregulating IL-6 and VEGF expression, and the restoration of
      KAI1 functionality offered a new approach in human melanoma treatment. 

PMID- 26199095
TI  - Hospitalist attitudes toward the assessment and management of dyspnea in patients
      with acute cardiopulmonary diseases.
AB  - BACKGROUND: Dyspnea is a common symptom in patients hospitalized with acute
      cardiopulmonary diseases. Routine assessment of dyspnea severity is recommended
      by clinical guidelines based on the evidence that patients are not treated
      consistently for dyspnea relief. OBJECTIVE: To evaluate attitudes and beliefs of
      hospitalists regarding the assessment and management of dyspnea. DESIGN: Cross
      sectional survey. SETTINGS: Nine hospitals in the United States. MEASUREMENTS:
      Survey questions assessed the following domains regarding dyspnea: importance in
      clinical care, potential benefits and challenges of implementing a standardized
      assessment, current approaches to assessment, and how awareness of severity
      affects management. A 5-point Likert scale was used to assess the respondent's
      level of agreement; strongly agree and agree were combined into a single
      category. RESULTS: Of the 255 hospitalists invited to participate, 69.8%
      completed the survey; 77.0% agreed that dyspnea relief is an important goal when
      treating patients with cardiopulmonary conditions. Approximately 90% of
      respondents stated that awareness of dyspnea severity influences their decision
      to intensify treatment, to pursue additional diagnostic testing, and the timing
      of discharge. Of the respondents, 61.0% agreed that standardized assessment of
      dyspnea should be part of the vital signs, and 64.6% agreed that awareness of
      dyspnea severity influences their decision to prescribe opioids. Hospitalists who
      appreciated the importance of dyspnea in clinical practice were more likely to
      support the implementation of a standardized scale. CONCLUSIONS: Most
      hospitalists believe that routine assessment of dyspnea severity would enhance
      their clinical decision making and patient care. Measurement and documentation of
      dyspnea severity may represent an opportunity to improve dyspnea management.

PMID- 26199096
TI  - Experiences with and Outcomes of Two Interventions to Maximize Engagement of
      Chronically Ill Adolescents During Hospital Consultations: A Mixed Methods Study.
AB  - Improving patient-provider communication during hospital consultations is
      advocated to enhance self-management planning and transition readiness of
      adolescents with chronic conditions. This longitudinal mixed methods study
      evaluates the implementation and the outcomes of independent split-visit
      consultations and individual transition plans by 22 hospital teams participating
      in the Dutch Action Program 'On Your Own Feet Ahead!'. The interventions raised
      awareness in adolescents and professionals, improved adolescents' display of
      independent behaviors and led to more discussions about non-medical issues.
      Successful implementation required a team-based approach and clear explanation to
      parents and adolescents. Pediatric nurses played a pivotal role in improving
      transitional care. 

PMID- 26199097
TI  - Transfer to Adult Care--Experiences of Young Adults with Congenital Heart
      Disease.
AB  - More than 90% of children born with congenital heart disease survive into
      adulthood due to successes of cardiac surgery and medical management. Interviews
      with 16 young adults with congenital heart disease to explore their experiences
      of transfer from pediatric to adult care were performed. The analysis identified
      five themes; Feeling secure during the transfer process, Experiencing trust in
      the care, Expecting to be involved, Assuming responsibility for one's health is a
      process and Lack of knowledge leads to uncertainty. In conclusion; a structured
      and gradual transfer process was necessary to enable the informants to shoulder
      the responsibility for self-care. 

PMID- 26199098
TI  - Psychophysical Effects of Increasing Oil Concentrations on Saltiness and
      Bitterness Perception of Oil-in-Water Emulsions.
AB  - Limited research has been done to investigate saltiness and bitterness
      perceptions of NaCl, KCl, and caffeine in emulsion systems. Saltiness and
      bitterness intensities of emulsions prepared with different concentrations of oil
      [0% (that is, solution), 20%, 40%, canola oil] and different concentrations of 3
      tastants (NaCl [0.5% to 1.0%], KCl [0.5% to 1.5%], and caffeine [0.05 to 0.15%])
      were measured using the SpectrumTM descriptive method (N = 16) and the Electronic
      tongue (E-tongue). Linear regression and the Stevens' power law were used to
      model the taste intensities against the tastant concentrations. From the
      descriptive data, saltiness intensities in emulsions were higher than solutions,
      demonstrating a saltiness-enhancing effect imparted by oil. Bitterness
      intensities in emulsions were lower compared to those of solutions for caffeine,
      but they were similar for KCl. This demonstrated that oil suppressed bitterness
      for caffeine. E-tongue saltiness measurements were corresponding to those of the
      descriptive data; however, E-tongue bitterness intensities of KCl showed an
      opposite pattern. 

PMID- 26199099
TI  - High-speed isocratic and gradient liquid-chromatography separations at 1500bar.
AB  - The need to improve either sample throughput on separation efficiency has spurred
      the development of ultra-high-pressure LC instrumentation, allowing to operate up
      to column pressures of 1500bar. In the present study, the isocratic and gradient
      performance limits were assessed at UHPLC conditions applying columns packed with
      core-shell particles. First, the extra-column band broadening contributions were
      assessed and minimized. Using an optimized system configuration minimum reduced
      plate heights of 1.8 were recorded on 2.1*100 columns packed with 1.5MUm core
      shell particles. Increasing the pressure limit from 500 to 1500bar and at the
      same time reducing the particle size from 2.6 to 1.5MUm has allowed the analysis
      time to be decreased by a factor of 1.5 in isocratic mode, while maintaining
      separation efficiency (N=54,000). The kinetic time-gain factor in isocratic mode
      was proportional to the ratio of the separation impedance of both columns
      multiplied with the pressure ratio applied. In addition, the effect of operating
      pressure on the time gain factor was assessed in gradient mode. Using optimized
      gradient steepness (tG/t0=12) and increasing the operating pressure from 500 to
      1500bar a time gain factor of almost 13 was achieved for the separation of a
      mixture of waste-water pollutants without compromising peak capacity. 

PMID- 26199100
TI  - In-situ suspended aggregate microextraction: A sample preparation approach for
      the enrichment of organic compounds in aqueous solutions.
AB  - This work presents in-situ suspended aggregate microextraction (iSAME) as a new
      and expedient sample preparation method. This new concept capitalizes on the
      general principles of in-situ solvent formation microextraction, in the sense
      that extraction is carried out in a supramolecular aggregate phase, which is
      formed in-situ in the sample through one-step process involving ion-association
      between a cationic surfactant and a benzene sulfonic acid derivative. The
      suspended aggregate containing the analytes is then collected in the form of a
      thin-film on the surface of a common filter paper by suction filtration. The
      entrapped analytes are released by completely dissolving the thin-film with a
      small volume of an organic solvent which is used for analysis. Using a series of
      organic UV filters as model analytes, the experimental variables pertaining to
      the operation of this new extraction approach were optimized and validated to the
      analysis of genuine water samples of different nature and with different matrix
      complexity (tap, river, lake, lagoon, delta and sea). The satisfactory analytical
      performance of the method in terms of recovery rates (80-112%), precision (0.9
      11.5%), high linearity of the calibration curves over a concentration range of 3
      orders of magnitude, the high selectivity along with its simplicity and low
      resource requirements render the method as an attractive alternative to the
      routine assessment of organic compounds in environmental water samples. 

PMID- 26199101
TI  - Trace-level determination of sweeteners in sewage sludge using selective
      pressurized liquid extraction and liquid chromatography-tandem mass spectrometry.
AB  - The occurrence of sweeteners in the environment has become a matter of concern
      due to the possibility of adverse effects on human health and wildlife species.
      One of the routes by which sweeteners enter the environment is through sewage
      sludge. Therefore, a method was developed with a selective-pressurized liquid
      extraction (S-PLE) followed by liquid chromatography-tandem mass spectrometry for
      the simultaneous determination of eight sweeteners in sewage sludge. The
      chromatographic separation was achieved in less than ten minutes using an amide
      polar-embedded reversed-phase column. Due to the high matrix effect present in
      the sample, an extensive study was conducted in order to overcome this issue,
      with C18 in-cell and solid-phase extraction (Oasis HLB) as a clean-up method. S
      PLE/SPE recoveries at two levels of concentration (50MUg/kg and 1000MUg/kg in dry
      weight (d.w.), n=5) were higher than 61%. Repeatability and reproducibility at
      the same concentrations (%RSD, n=5) were lower than 11% and 16%, respectively.
      The limits of detection were 10MUg/kg (d.w) for all compounds, except for
      cyclamate (5MUg/kg (d.w.)). The method was successfully applied to sewage sludge
      samples from three sewage treatment plants located in Catalonia (Spain). Of the
      eight compounds, five were determined in all of the samples analysed, with
      acesulfame and saccharine being recorded at the highest concentrations of up to
      481MUg/kg and 591MUg/kg (d.w.), respectively. 

PMID- 26199102
TI  - Detailed study of imatinib metabolization using high-resolution mass
      spectrometry.
AB  - Modern high resolution mass spectrometry offers unique identification capability
      in drug metabolism studies. In this work detailed imatinib metabolization in the
      plasma of patients with chronic myeloid leukemia is presented. The metabolites
      were separated by liquid chromatography on a C18 column with mass spectrometry
      detection via an Orbitrap Elite instrument (Thermo Scientific) based on exact
      mass measurement. A scan range of m/z 350-1200 resolution of 60,000 was applied
      (mass accuracy of 5ppm). The data were evaluated using the advanced software for
      mass spectrometry Mass Frontier and MetWorks. In all plasma samples, studied 90
      metabolites in the concentration range of 0.0001-1MUmol/L were identified by m/z
      values and confirmed by exact mass measurement of the MS(2) and MS(3)
      fragmentations. In order to achieve optimal clinical response and avoid toxicity,
      current therapeutic monitoring of parent drug is a useful tool for the
      individualization of treatment. Current high-resolution mass spectrometry
      possesses the potential to broaden this approach by monitoring number of
      potentially clinically relevant drug metabolites. 

PMID- 26199103
TI  - Biocompatible chiral monolithic stationary phase synthesized via atom transfer
      radical polymerization for high performance liquid chromatographic analysis.
AB  - Novel biocompatible chiral monolithic stationary phase was prepared by reverse
      and direct atom transfer radical polymerization (ATRP) methods. By taking
      advantages of the controlled/living property of ATRP method, the chiral monolith
      was prepared by reverse ATRP (RATRP) firstly. An attractive feature of RATRP is
      the prepared polymer containing a terminal radically transferable atom that can
      initiate another post-polymerization reaction by direct ATRP. Then, the
      biocompatible poly(hydroxyethyl methacrylate) (PHEMA) was grafted on the surface
      of the chiral monolith by direct ATRP as a diffusion barrier for proteins. This
      biocompatible chiral monolith was successfully used as restricted access
      stationary phase for determination of enantiomers in biological samples with
      direct injection by high-performance liquid chromatography (HPLC). 

PMID- 26199104
TI  - Assessment of volatile compound profiles and the deduced sensory significance of
      virgin olive oils from the progeny of Picual*Arbequina cultivars.
AB  - Volatile compounds are responsible for most of the sensory qualities of virgin
      olive oil and they are synthesized when enzymes and substrates come together as
      olive fruit is crushed during the industrial process to obtain the oil. Here we
      have studied the variability among the major volatile compounds in virgin olive
      oil prepared from the progeny of a cross of Picual and Arbequina olive cultivars
      (Olea europaea L.). The volatile compounds were isolated by SPME, and analyzed by
      HRGC-MS and HRGC-FID. Most of the volatile compounds found in the progeny's oil
      are produced by the enzymes in the so-called lipoxygenase pathway, and they may
      be clustered into different groups according to their chain length and
      polyunsaturated fatty acid origin (linoleic and linolenic acids). In addition, a
      group of compounds derived from amino acid metabolism and two terpenes also
      contributed significantly to the volatile fraction, some of which had significant
      odor values in most of the genotypes evaluated. The volatile compound content of
      the progeny was very varied, widely transgressing the progenitor levels,
      suggesting that in breeding programs it might be more effective to consider a
      larger number of individuals within the same cross than using different crosses
      with fewer individuals. Multivariate analysis allowed genotypes with particularly
      interesting volatile compositions to be identified and their flavor quality
      deduced. 

PMID- 26199107
TI  - Pro-aromatic bisphenaleno-thieno[3,2-b]thiophene versus anti-aromatic bisindeno
      thieno[3,2-b]thiophene: different ground-state properties and applications in
      field-effect transistors.
AB  - A pro-aromatic bisphenaleno-thieno[3,2-b]thiophene (BPT-TIPS) was synthesized and
      compared with an anti-aromatic bisindeno-thieno[3,2-b]thiophene (S2-TIPS). BPT
      TIPS showed larger diradical character, stronger absorption, longer excited state
      lifetime and better redox amphotericity than S2-TIPS.

PMID- 26199108
TI  - Impact of disease, cognitive and behavioural factors on caregiver outcome in
      amyotrophic lateral sclerosis.
AB  - Up to 50% of patients with amyotrophic lateral sclerosis (ALS) show mild to
      moderate cognitive-behavioural change alongside their progressive functional
      impairment. This study examines the relative impact of patients' disease
      symptoms, behavioural change and current executive function and social cognition
      abilities on psychosocial outcomes in spouse caregivers of people with ALS.
      Thirty-five spouse caregivers rated their own levels of depression and anxiety,
      subjective burden and marital satisfaction. Caregivers also rated their partner's
      everyday behaviour. The patients were assessed for disease severity and cognitive
      function, with composite scores derived for executive function and social
      cognition. Regression analyses revealed that caregiver burden was predicted by
      the severity of patients' limb involvement and behavioural problems. Depression
      was predicted by patients' limb involvement, while behavioural problems and
      patient age predicted caregiver anxiety. Current marital satisfaction was
      predicted by patient behavioural problems beyond the level of pre-illness marital
      satisfaction. In conclusion, the study highlights the potential impact of ALS
      patients' functional impairment and behavioural change on ALS caregivers'
      psychosocial functioning. Clinical communication with ALS families should
      emphasise both physical and psychological challenges presented by the disease. 

PMID- 26199109
TI  - A novel Arg147Trp MATR3 missense mutation in a slowly progressive ALS Italian
      patient.

PMID- 26199110
TI  - Interleukin-27 and IFNgamma regulate the expression of CXCL9, CXCL10, and CXCL11
      in hepatitis.
AB  - Interleukin-27 (IL-27) belongs to the IL-6/IL-12 family of cytokines, associated
      with different inflammatory diseases and orchestrates its biological activity via
      common heterodimeric receptor composed of WSX-1 (IL-27Ralpha) and gp130. The
      present study was aimed to investigate the regulation of CXCL9, CXCL10, and
      CXCL11 chemokines in hepatic cells (human LX-2 cell line derived from normal
      human stellate cells (HSC), primary human hepatocytes, HSC, and HepG2 cells) and
      concanavalin A (ConA)-induced liver inflammation. We demonstrated that IL-27, but
      not IL-6, induced/up-regulated CXCR3 ligand genes (CXCL9, CXCL10, and CXCL11; out
      of 26 selected genes) in a STAT1-dependent manner in hepatic cells in vitro both
      at transcript and protein levels. In ConA-induced T cell-mediated hepatic model,
      we showed that soluble IL-27/IFNgamma was elevated following ConA hepatitis in
      association with increased CXCL9, CXCL10, and CXCL11 expression in the liver. The
      exogenous IL-27 administration induced CXCR3 ligands in mouse liver at 4 h with
      any significant effect on recruitment of CXCR3(+) immune cells in the liver. The
      neutralization of IL-27 during ConA hepatitis differentially modulated
      (transcript vs protein expression) CXCR3 ligands and IFNgamma during ConA-induced
      hepatitis with down-regulated expression of CXCL9 and CXCL10 at transcript level.
      The IFNgamma, complementary regulated the expression of CXCR3 ligands as their up
      regulation during ConA hepatitis, was abolished in IFNgamma KO mice. In summary,
      IL-27 up-regulated the CXCL9, CXCL10, and CXCL11 chemokine expression in hepatic
      cells. IL-27 regulated CXCR3 ligand expression in IFNgamma-dependent manner
      during acute hepatitis suggesting a complementary role of IL-27 and IFNgamma to
      moderate liver inflammation via regulation of CXCR3 ligands. KEY MESSAGE: IL-27
      up-regulated CXCR3 ligand expression in human hepatic cells in vitro. IL-27 up
      regulated CXCR3 ligand expression and secretion in ConA hepatitis in vivo. CXCR3
      ligand expression was down-regulated by blocking IL-27 or IFNgamma deficiency. IL
      27 modulated liver injury by regulation of CXCR3 ligands in IFNgamma-dependent
      manner.

PMID- 26199111
TI  - Growth hormone replacement therapy regulates microRNA-29a and targets involved in
      insulin resistance.
AB  - Replacement of growth hormone (GH) in patients suffering from GH deficiency (GHD)
      offers clinical benefits on body composition, exercise capacity, and skeletal
      integrity. However, GH replacement therapy (GHRT) is also associated with insulin
      resistance, but the mechanisms are incompletely understood. We demonstrate that
      in GH-deficient mice (growth hormone-releasing hormone receptor
      (Ghrhr)(lit/lit)), insulin resistance after GHRT involves the upregulation of the
      extracellular matrix (ECM) and the downregulation of microRNA miR-29a in skeletal
      muscle. Based on RNA deep sequencing of skeletal muscle from GH-treated
      Ghrhr(lit/lit) mice, we identified several upregulated genes as predicted miR-29a
      targets that are negative regulators of insulin signaling or
      profibrotic/proinflammatory components of the ECM. Using gain- and loss-of
      function studies, five of these genes were confirmed as endogenous targets of miR
      29a in human myotubes (PTEN, COL3A1, FSTL1, SERPINH1, SPARC). In addition, in
      human myotubes, IGF1, but not GH, downregulated miR-29a expression and
      upregulated COL3A1. These results were confirmed in a group of GH-deficient
      patients after 4 months of GHRT. Serum IGF1 increased, skeletal muscle miR-29a
      decreased, and miR-29a targets were upregulated in patients with a reduced
      insulin response (homeostatic model assessment of insulin resistance (HOMA-IR))
      after GHRT. We conclude that miR-29a could contribute to the metabolic response
      of muscle tissue to GHRT by regulating ECM components and PTEN. miR-29a and its
      targets might be valuable biomarkers for muscle metabolism following GH
      replacement. KEY MESSAGES: GHRT most significantly affects the ECM cluster in
      skeletal muscle from mice. GHRT downregulates miR-29a and upregulates miR-29a
      targets in skeletal muscle from mice. PTEN, COL3A1, FSTL1, SERPINH1, and SPARC
      are endogenous miR-29a targets in human myotubes. IGF1 decreases miR-29a levels
      in human myotubes. miR-29a and its targets are regulated during GHRT in skeletal
      muscle from humans.

PMID- 26199113
TI  - Integrated PET/MRI for whole-body staging of patients with primary cervical
      cancer: preliminary results.
AB  - PURPOSE: To assess the diagnostic value of integrated PET/MRI for whole-body
      staging of cervical cancer patients, as well as to investigate a potential
      association between PET/MRI derived functional parameters and prognostic factors
      of cervical cancer. METHODS: The present study was approved by the local
      institutional review board. Twenty-seven patients with histopathologically
      confirmed cervical cancer were prospectively enrolled in our study. All patients
      underwent a whole-body PET/MRI examination after written informed consent was
      obtained. Two radiologists separately evaluated the PET/MRI data sets regarding
      the determination of local tumor extent of primary cervical cancer lesions, as
      well as detection of nodal and distant metastases. Furthermore, SUV and ADC
      values of primary tumor lesions were analyzed and correlated with dedicated
      prognostic factors of cervical cancer. Results based on histopathology and cross
      sectional imaging follow-up served as the reference standard. RESULTS: PET/MRI
      enabled the detection of all 27 primary tumor lesions of the uterine cervix and
      allowed for the correct determination of the T-stage in 23 (85 %) out of the 27
      patients. Furthermore, the calculated sensitivity, specificity and diagnostic
      accuracy for the detection of nodal positive patients (n = 11) were 91 %, 94 %
      and 93 %, respectively. PET/MRI correctly identified regional metastatic disease
      (N1-stage) in 8/10 (80 %) patients and non-regional lymph node metastases in 5/5
      (100 %) patients. In addition, quantitative analysis of PET and MRI derived
      functional parameters (SUV; ADC values) revealed a significant correlation with
      pathological grade and tumor size (p < 0.05). CONCLUSIONS: The present study
      demonstrates the high potential of integrated PET/MRI for the assessment of
      primary tumor and the detection of lymph node metastases in patients with
      cervical cancer. Providing additional prognostic information, PET/MRI may serve
      as a valuable diagnostic tool for cervical cancer patients in a pretreatment
      setting.

PMID- 26199112
TI  - The ins and outs of adrenergic signaling.
AB  - Adrenergic signaling, in particular signaling in the sympathetic nervous system,
      is a prime example of the control of an essential physiological system. It has
      served as a model system both for the control of mediator release and for
      receptor signaling and regulation. This review covers the historical development
      of the field and then addresses issues that represent key fields of ongoing
      research: the mechanisms and kinetics of receptor activation, temporal patterns
      of downstream signaling and signal bias, receptor mobility and aggregation, and
      signal compartmentation and specificity. The available evidence suggests that
      adrenergic signaling may involve complex spatiotemporal patterns, which give
      texture to the signaling process and may contain additional biological
      information. 

PMID- 26199114
TI  - Stereoselective alpha-indolylation of enals via an organocatalytic formal cross
      coupling with indoles.
AB  - We report a novel organocatalytic one-pot cascade bromination-Michael-type
      Friedel-Crafts alkylation dearomatization-nucleophilic rearrangement
      aromatization cascade process for the direct alpha-indolylation of
      unfunctionalized enals from readily available indoles with good yields and high E
      selectivity. The simplicity and practicality of its high efficiency for formation
      of a new C(sp(2))-C(sp(2)) bond constitute the most attractive advantage of this
      reaction. 

PMID- 26199115
TI  - Genetic and Non-Genetic Determinants of Circulating Levels of Adiponectin in a
      Cohort of Chilean Subjects.
AB  - BACKGROUND: Low adiponectin levels have been associated with obesity, diabetes,
      coronary disease and polymorphisms. The aim of this study was to assess the
      clinical and genetic factors related to adiponectin levels in a Chilean adult
      population. METHODS: Four groups of 27 individuals, stratified by gender and
      abdominal obesity, were included in this cross-sectional study. Physical activity
      level, cardiovascular risk factors and therapy were assessed. Anthropometric
      measurements, adiponectin, glucose, insulin, hs-CRP, rs1501299, rs2241766,
      rs266729 and rs17300539 single nucleotide polymorphisms of the adiponectin gene
      were determined. RESULTS: Adiponectin levels were inversely correlated with waist
      circumference, waist-to-hip ratio, weight, body mass index, insulin levels,
      homeostasis model insulin resistance index (HOMA-IR) and physical activity. Mean
      adiponectin levels were lower in men (10.1 +/- 3.6 vs 11.9 +/- 2.9 MUg/mL, p =
      0.0051), obese (9.9 +/- 3.2 vs 12.1 +/- 3.3, p < 0.01), physically inactive (8.9
      +/- 3.2 vs 11.0 +/- 2.8, p = 0.015) and insulin-resistant individuals (10.2 +/-
      3.1 vs 12.9 +/- 3.9; p = 0.005). Adiponectin levels were lower in subjects with
      GG genotype (rs1501299) compared with those with TT or GT variants (6.9 +/- 4.6
      vs 12.2 +/- 2.9 and 11.5 +/- 3.4 MUg/mL, p = 0.006) but were similar in the other
      polymorphisms studied. CONCLUSION: Lower adiponectin levels were related to
      gender, abdominal obesity, physical activity and insulin resistance and were less
      influenced by the polymorphisms studied.

PMID- 26199116
TI  - Provision of information leaflet before urodynamic study reduces the pre
      examination anxiety level.
AB  - AIMS: To find out if information leaflets reduce anxiety levels before urodynamic
      studies (UDS). METHODS: One hundred and four patients (age 60 +/- 15 years) who
      were referred for multichannel UDS were prospectively recruited and randomized
      into 2 groups: (1) received a leaflet containing detailed information regarding
      the examination; (2) did not receive a leaflet. Patients who were unable to
      complete the questionnaire due to mental disorders and patients who had
      previously undergone UDS were excluded. The leaflets were mailed to the patients
      in group 1 one month before the examination. This leaflet included information on
      how the examination would be performed, its purpose, recommended preparation,
      potential complications, and common events that might occur in association with
      the examination, such as incontinence. Emotional distress was measured by the
      State Anxiety Inventory (SAI)-a validated questionnaire composed of 20 items
      measuring anxiety. These measures are divided into two psychological domains: (1)
      positive well being; (2) psychological distress. Patients filled out the SAI
      immediately before entering the examination room. RESULTS: Demographics and
      clinical and psychological co-morbidities were similar between the groups. The
      "psychological distress" score was significantly lower in group 1 (13.1 +/- 2.9
      vs. 24.8 +/- 5.8, P < 0.001), whereas there was no difference in the "positive
      well being" score. CONCLUSIONS: We recommend providing patients with an
      information leaflet on UDS since it significantly reduces anxiety levels.
      Neurourol. Urodynam. 35:805-808, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26199117
TI  - Mineralocorticoid Receptor Antagonism in Acute Heart Failure.
AB  - OPINION STATEMENT: Heart failure (HF) remains a tremendous burden to health care
      systems and patients worldwide. The cornerstone neurohormonal disruption that
      leads to the debilitating sequelae in HF patients revolves primarily around
      aldosterone and the renin-angiotensin-aldosterone system (RAAS). Aldosterone
      plays a detrimental role in tissue remodeling by inducing inflammation and
      fibrosis within the cardiovascular and renal systems, leaving mineralocorticoid
      receptor antagonists (MRAs) as key pharmacological tools to slow pathogenesis and
      improve patient outcomes. The role of MRA in improving morbidity and mortality in
      outpatients with chronic HF and low ejection fraction is well established and
      supported by large randomized controlled trials. However, evidence-based data
      relating to the use of MRA in acute HF (AHF) remain somewhat limited, and
      therefore, the use of MRA is not ubiquitously considered in the acute setting.
      Current studies for the use of MRA in AHF are limited by small sample size as
      well as safety concerns relating to the dose-dependent effects on electrolyte
      homeostasis and renal function. Here, we discuss the imperative need for
      additional trials elucidating the potential benefits of MRA in AHF as an adjunct
      diuretic therapy. We not only discuss the role of MRA in neurohormonal regulation
      of aldosterone but also highlight a potential dose-dependent role for MRA in
      natriuresis. Furthermore, we showcase existing and recent evidence-based data
      demonstrating the effectiveness of MRA in AHF and on long-term outcomes. Finally,
      we look at several treatment strategies and safety concerns as they relate to MRA
      use so as to aid in avoidance of MRA-related complications while facilitating
      achievement of treatment goals.

PMID- 26199118
TI  - Synthesis and anti-tubercular activity of 2-nitroimidazooxazines with
      modification at the C-7 position as PA-824 analogs.
AB  - Tuberculosis (TB) is a major global health problem, and new drug targets and
      scaffolds need to be identified to combat the emergence of drug resistant TB. The
      nitroimidazooxazine PA-824 represents a new class of bio-reductive drug to treat
      TB. In this study we report a 2-nitroimidazooxazine derivative with modification
      at the C-7 position that exhibited better activity than PA-824 against
      Mycobacterium tuberculosis (Mtb) H37Rv strain in vitro. From 7a as a key
      intermediate, we functionalized with benzyl ether (8), phenyl ether (9), benzyl
      carbonate (10) and benzyl carbamate (11). Among the 23 compounds produced, 8a-R
      (MIC=0.078 MUM) with trifluoromethoxy benzyl group was 5-fold more potent than PA
      824 (MIC=0.390 MUM) in the in vitro assays against the wild-type Mtb, and the
      phenyl ether compound 9g-R (MIC=0.050 MUM) exhibited the most potent
      antimycobacterial activity.

PMID- 26199119
TI  - Identification and optimisation of 4,5-dihydrobenzo[1,2-d:3,4-d]bisthiazole and
      4,5-dihydrothiazolo[4,5-h]quinazoline series of selective phosphatidylinositol-3
      kinase alpha inhibitors.
AB  - A cyclisation within a 4',5-bisthiazole (S)-proline-amide-urea series of
      selective PI3Kalpha inhibitors led to a novel 4,5-dihydrobenzo[1,2-d:3,4
      d]bisthiazole tricyclic sub-series. The synthesis and optimisation of this 4,5
      dihydrobenzo[1,2-d:3,4-d]bisthiazole sub-series and the expansion to a related
      tricyclic 4,5-dihydrothiazolo[4,5-h]quinazoline sub-series are described. From
      this work analogues including 11, 12, 19 and 23 were identified as potent and
      selective PI3Kalpha inhibitor in vivo tool compounds. 

PMID- 26199120
TI  - Discovery of substituted (4-phenyl-1H-imidazol-2-yl)methanamine as potent
      somatostatin receptor 3 agonists.
AB  - We report SAR studies on a novel non-peptidic somatostatin receptor 3 (SSTR3)
      agonist lead series derived from (4-phenyl-1H-imidazol-2-yl)methanamine. This
      effort led to the discovery of a highly potent low molecular weight SSTR3 agonist
      5c (EC50=5.2 nM, MW=359). The results from molecular overlays of 5c onto the L
      129 structure indicate good alignment, and two main differences of the proposed
      overlays of the antagonist MK-4256 onto the conformation of 5c lead to inversion
      of antagonism to agonism.

PMID- 26199121
TI  - Novel inhibitor against Malassezia globosa LIP1 (SMG1), a potential anti-dandruff
      target.
AB  - Compelling evidence have demonstrated the role of lipase activity in the
      pathogenicity of Malassezia globosa toward dandruff and seborrheic dermatitis
      (D/SD). As a representative secreted lipase from M. globosa CBS 7966, Malassezia
      globosa LIP1 (SMG1) is considered a potential anti-dandruff target. In this
      study, homology modeling, docking-based virtual screening and in vitro lipase
      based assay were integrated to identify the first hit compound against SMG1, with
      an IC50 of 20 MUM against synthetic lipase substrate, and of 0.19 MUM when using
      natural lipase substrate. Evaluation of similar compounds, along with docking,
      offered information on the binding patterns of the hit compound. This work is
      expected to serve as a starting point for the rational design of more potent
      inhibitors against SMG1.

PMID- 26199122
TI  - Genetic meta-analysis of 15,901 African Americans identifies variation in EXOC3L1
      is associated with HDL concentration.
AB  - Meta-analyses of European populations has successfully identified genetic
      variants in over 150 loci associated with lipid levels, but results from
      additional ethnicities remain limited. Previously, we reported two novel lipid
      loci identified in a sample of 7,657 African Americans using a gene-centric array
      including 50,000 SNPs in 2,100 candidate genes. Initial discovery and follow-up
      of signals with P < 10(-5) in additional African American samples confirmed CD36
      and ICAM1. Using an additional 8,244 African American female samples from the
      Women's Health Initiative SNP Health Association Resource genome-wide association
      study dataset, we further examined the previous meta-analyses results by
      attempting to replicate 20 additional putative lipid signals with P < 10(-4).
      Replication confirmed rs868213, located in a splice donor region of exocyst
      complex component 3-like 1 (EXOC3L1) as a novel signal for HDL (additive allelic
      effect beta = 0.02; P = 1.4 * 10(-8); meta-analyses of discovery and
      replication). EXOC3L1 is strongly expressed in vascular endothelium and forms
      part of the exocyst complex, a key facilitator of the trafficking of lipid
      receptors. Increasing sample sizes for genetic studies in nonEuropean populations
      will continue to improve our understanding of lipid metabolism. 

PMID- 26199125
TI  - Corrigendum: Composite Aromatic Boxes for Enzymatic Transformations of Quaternary
      Ammonium Substrates.

PMID- 26199128
TI  - A lattice model for connectedness percolation in mixtures of rods and disks.
AB  - Geometric percolation in mixtures of isotropically oriented rods and disks is
      examined from the perspective of a tree-like lattice model with a distribution
      over the co-ordination numbers (or vertex degrees). Correlations between the
      particle locations are described within a mean-field approximation that employs
      operationally-defined parameters to characterize pairwise interactions. The
      percolation threshold is studied as a function of the particle size disparity and
      the strength of inter-particle correlations. For certain combinations of the
      particle size ratio and inter-particle interaction strength, the volume fraction
      at the percolation threshold is found to vary non-monotonically as a function of
      the composition of the mixture. 

PMID- 26199129
TI  - Variation analysis of E1 and E2 in HCV subtypes.
AB  - Pegylated interferon and ribavirin combination therapy effectively suppresses
      viral replication in 50 %-60 % of hepatitis C virus (HCV)-infected patients.
      However, HCV-infected patients often display varied responses to therapy, and
      strains of subtype lb (the most widespread HCV subtype worldwide) have more
      severe clinical manifestations, greater viral loads, and poorer responses to
      interferon treatment. Therefore, understanding the genomic variability of HCV is
      crucial to treatment of HCV infection. In this study, we used the appropriate
      software to analyze the nucleotide, and amino acid sequences of the envelope
      proteins (E1 and E2) of HCV to investigate the extent of their variability in
      several HCV subtypes (1a, 1b, 2a, 2b, 3a, 4a, 5a and 6a) and calculated the ratio
      of nonsynonymous to synonymous substitutions (dN/dS) in these proteins to
      investigate the immunological pressure acting on them. We also predicted the N
      glycosylation sites in E1 and E2 to determine their association with viral
      neutralization. We found that E1 is more variable, has a higher dN/dS ratio, and
      has more N-glycosylation sites than E2 in HCV subtype 1b. This indicates that the
      variability of E1, its dN/dS ratio, and its degree of N-glycosylation might play
      an important role in the treatment of infection with HCV subtype 1b. 

PMID- 26199130
TI  - Porosity and sealing ability of root fillings with gutta-percha and BioRoot RCS
      or AH Plus sealers. Evaluation by three ex vivo methods.
AB  - AIM: To investigate the ability of BioRoot RCS, a tricalcium silicate-based root
      canal sealer and AH Plus to effectively fill the root canals of contralateral
      teeth using three evaluation methods, and to investigate also the correlation
      between the methods. METHODOLOGY: The prepared root canals of ten pairs of
      contralateral mandibular premolar teeth were filled with gutta-percha and sealer
      using lateral compaction. The percentage of voids within the root canal was
      assessed by micro-computed tomography, whilst sealing ability was investigated by
      fluid transport and leakage of fluorescent microspheres. The interaction of
      sealer with dentine, and sealer penetration were assessed by confocal microscopy.
      The void volume, fluid flow, microsphere leakage and sealer interaction with
      dentine for both materials were compared. Nonparametric (Mann-Whitney) tests were
      used to compare the % void and fluid transport of the two sealers. Spearman
      correlation was used to assess the pairwise relationships between the techniques.
      The level of significance was set to 0.05. RESULTS: BioRoot RCS exhibited
      significantly more percentage of voids than AH Plus. There was no difference in
      fluid flow and microsphere penetration. BioRoot RCS exhibited a different pattern
      of sealer penetration and interaction with the dentine walls compared to AH Plus.
      For both materials, the pairwise correlations between the three techniques were
      close to zero, indicating weak relationships. CONCLUSIONS: MicroCT analysis
      revealed a higher void volume for BioRoot RCS. The other techniques did not show
      a difference between the sealing ability of the sealers. The correlation between
      the three ex vivo methods of assessment was weak demonstrating their
      complementarity rather than their concordance.

PMID- 26199131
TI  - Cyclin-dependent kinase regulatory subunit 1 promotes cell proliferation by
      insulin regulation.
AB  - Cyclin-dependent kinase regulatory subunit 1 (CKS1) helps regulate the cell cycle
      to increase cell number. However, the hormonal regulation on CKS1 expression is
      not well understood. We report that CKS1 is involved in the promotion of cell
      proliferation with insulin regulation in the lepidopteran insect Helicoverpa
      armigera. CKS1 is expressed in various tissues during the larval feeding stage.
      CKS1 knockdown results in larval death, body weight decrease, pupation time
      delay, and small-sized pupa formation. The underlying mechanism involves the
      blocking of cell proliferation and the repression of gene expression in the
      insulin pathway after CKS1 knockdown. CKS1 overexpression in the epidermal cell
      line results in cell proliferation. The N45 amino acid asparagine in the CKS
      domain is essential for the function of CKS in cell proliferation. CKS1 is
      upregulated by insulin via an insulin receptor, but is repressed by a high level
      of steroid hormone 20-hydroxyecdysone (20E). Results suggest that CKS1 promotes
      cell proliferation and body growth in coordination with the regulatory actions of
      insulin and steroid hormone 20E. 

PMID- 26199132
TI  - High proliferation index, as determined by immunohistochemical expression of
      Aurora kinase B and geminin, indicates poor prognosis in neuroblastomas.
AB  - Expression profile analysis of cell cycle biomarkers provides a powerful index of
      the proliferative state of tumors, which is linked to disease aggressiveness. We
      investigated the impact of the biomarkers of S-G2-M phases of cell cycle, Aurora
      kinase B (AURKB) and geminin (GMNN), on disease progression in neuroblastomas.
      The expression of AURKB and GMNN was studied by immunostaining 84 neuroblastomas.
      A proliferation index (PI) was obtained on scanned immunostained slides using
      image analysis software. The median PI was 8.5 % for AURKB- and 16.8 % for GMNN
      stained slides with a high correlation between the two (r s = 0.72, P < 0.001).
      The PI for both markers was significantly higher in neuroblastomas from patients
      with unfavorable clinical (high-risk group, advanced stage, age >=18 months at
      presentation, primary abdominal compared to extra-abdominal sites), biological
      (MYCN amplification, 1p deletion, 17q gain), and pathological (undifferentiated
      or poorly differentiated status, high mitosis-karyorrhexis index, [MKI],
      unfavorable histology) factors. Using Cox regression models, a higher-than-median
      AURKB and GMNN PI was associated with a significantly shorter overall survival
      (OS) and event-free survival (EFS) in univariable analysis. In multivariable
      analysis, a high AURKB PI was associated with significantly shorter OS and EFS,
      independent of MYCN amplification, and significantly shorter EFS, independent of
      MKI. High GMNN PI was also associated with significantly shorter OS and EFS after
      adjusting for MYCN amplification but failed to reach statistical significance
      after adjusting for MKI. Our study shows that in neuroblastomas, AURKB- or GMNN
      based PI provides valuable prognostic information and high PI indicates
      aggressive disease.

PMID- 26199133
TI  - The role of the Carer Support Needs Assessment Tool in palliative home care: A
      qualitative study of practitioners' perspectives of its impact and mechanisms of
      action.
AB  - BACKGROUND: The importance of supporting family carers is well recognised in
      healthcare policy. The Carer Support Needs Assessment Tool is an evidence-based,
      comprehensive measure of carer support needs to facilitate carer support in
      palliative home care. AIM: To examine practitioner perspectives of the role of
      the Carer Support Needs Assessment Tool intervention in palliative home care to
      identify its impact and mechanisms of action. DESIGN: Qualitative - practitioner
      accounts of implementation (interviews, focus groups, reflective audio diaries)
      plus researcher field notes. SETTING/PARTICIPANTS: A total of 29 staff members
      from two hospice home-care services - contrasting geographical locations,
      different service sizes and staff composition. A thematic analysis was conducted.
      RESULTS: Existing approaches to identification of carer needs were informal and
      unstructured. Practitioners expressed some concerns, pre-implementation, about
      negative impacts of the Carer Support Needs Assessment Tool on carers and
      expectations raised about support available. In contrast, post-implementation,
      the Carer Support Needs Assessment Tool provided positive impacts when used as
      part of a carer-led assessment and support process: it made support needs
      visible, legitimised support for carers and opened up different conversations
      with carers. The mechanisms of action that enabled the Carer Support Needs
      Assessment Tool to make a difference were creating space for the separate needs
      of carers, providing an opportunity for carers to express support needs and
      responding to carers' self-defined priorities. CONCLUSION: The Carer Support
      Needs Assessment Tool delivered benefits through a change in practice to an
      identifiable, separate assessment process for carers, facilitated by
      practitioners but carer-led. Used routinely with all carers, the Carer Support
      Needs Assessment Tool has the potential to normalise carer assessment and
      support, facilitate delivery of carer-identified support and enable effective
      targeting of resources.

PMID- 26199134
TI  - Estimating the cost of caring for people with cancer at the end of life: A
      modelling study.
AB  - BACKGROUND: People with advanced cancer require a range of health, social and
      informal care during the final phases of life. The cost of providing care to this
      group as they approach the end of their lives is unknown, but represents a
      significant cost to health and social care systems, charities patients and their
      families. AIM: In this study, we estimate the direct and indirect costs for lung,
      breast, colorectal and prostate cancer patients at the end of life (from the
      start of strong opioids to death) in England and Wales. METHODS: We use a
      modelling-based approach to estimate the costs of care. Data are estimated from
      the literature and publicly available data sets. Probabilistic sensitivity
      analysis is used to reflect uncertainty in model estimates. RESULTS: Total
      estimated costs for treating people with these four cancers at the end of life
      are L 641 million. Breast and prostate cancer patients have the highest expected
      cost per person at L 12,663 (95% credible interval (CI): L 1249-L 38,712) and L
      14,859 (95% CI: L 1391-L 46,424), respectively. Lung cancer has the highest
      expected total cost (L 226 m). The value of informal care giving accounts for
      approximately one-third of all costs. CONCLUSION: The cost to society of
      providing care to people at the end of their lives is significant. Much of this
      cost is borne by informal care givers. The cost to formal care services of
      replacing this care with paid care giving would be significant and demand for
      care will increase as the demographic profile of the population ages.

PMID- 26199135
TI  - Allergic reaction to ortho-phthalaldehyde following flexible laryngoscopy.
AB  - Flexible laryngoscopes are common outpatient surveillance tools. Cleansing of
      these scopes between patients must be quick, effective, and safe. One sterilant
      that largely meets these criteria is ortho-phthalaldehyde (OPA); however,
      infrequently, patients may develop allergic reactions to it. We present three
      cases of patients who developed significant allergic reactions following repeated
      laryngoscopic examinations. Subsequent intradermal allergy testing confirmed
      sensitivity to OPA. In addition, we reviewed the current literature, which
      includes 17 similar reactions reported in nine patients across disciplines.
      Allergic reaction to OPA is uncommon, but a potentially under-reported severe
      complication of repeated endoscopy.

PMID- 26199137
TI  - Otoacoustic emissions in newborns evoked by 0.5kHz tone bursts.
AB  - BACKGROUND: Otoacoustic emissions (OAEs) are currently widely used in newborn
      hearing screening programs. OAEs evoked by transients (TEOAEs) in newborns are
      usually characterized by large response levels at higher frequencies but lower
      frequencies are affected by physiological noise. The purpose of the present study
      was to acquire responses at lower frequencies by measuring OAEs evoked by 0.5kHz
      tone bursts (TBOAEs). METHODS: Otoacoustic emissions (OAEs) were recorded from 49
      newborns. Measurements were made using the ILO 292 equipment from Otodynamics. In
      each ear, three measurements were made: first with a standard click stimulus at
      80dB pSPL (CEOAEs), a second using a 0.5kHz tone burst at 80dB pSPL (TBOAEs), and
      a third recording of spontaneous OAEs (SOAEs). Global and half-octave-band values
      of OAE signal-to-noise ratio (SNR) and response level were used to assess
      statistical differences between CEOAEs and 0.5kHz TBOAEs. Additionally, time
      frequency (TF) analysis of signals was performed using the matching pursuit
      method. RESULTS: Global levels were highest for CEOAEs. However, at low
      frequencies (0.7-1kHz), 0.5kHz TBOAEs had significantly higher levels and SNRs
      than CEOAEs. At these frequencies, SNRs of CEOAEs were usually below 0dB. At
      0.5kHz there were no statistically significant differences between CEOAEs and
      TBOAEs. In ears with recordable SOAEs, CEOAEs and TBOAEs had higher levels and
      SNRs than in ears without SOAEs. CONCLUSIONS: Use of 0.5kHz TBOAEs may be a
      useful addition to standard CEOAE tests in newborns. They provide information
      about lower frequencies, a region where CEOAEs are usually prone to noise. The
      presence of SOAEs affects the magnitudes of both CEOAEs and TBOAEs.

PMID- 26199136
TI  - Stimulation of nuclear receptor peroxisome proliferator-activated receptor-gamma
      limits NF-kappaB-dependent inflammation in mouse cystic fibrosis biliary
      epithelium.
AB  - Cystic fibrosis-associated liver disease is a chronic cholangiopathy that
      negatively affects the quality of life of cystic fibrosis patients. In addition
      to reducing biliary chloride and bicarbonate secretion, up-regulation of toll
      like receptor 4/nuclear factor kappa light-chain-enhancer of activated B cells
      (NF-kappaB)-dependent immune mechanisms plays a major role in the pathogenesis of
      cystic fibrosis-associated liver disease and may represent a therapeutic target.
      Nuclear receptors are transcription factors that regulate several intracellular
      functions. Some nuclear receptors, including peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma), may counterregulate inflammation in a tissue
      specific manner. In this study, we explored the anti-inflammatory effect of PPAR
      gamma stimulation in vivo in cystic fibrosis transmembrane conductance regulator
      (Cftr) knockout mice exposed to dextran sodium sulfate and in vitro in primary
      cholangiocytes isolated from wild-type and from Cftr-knockout mice exposed to
      lipopolysaccharide. We found that in CFTR-defective biliary epithelium expression
      of PPAR-gamma is increased but that this does not result in increased receptor
      activity because the availability of bioactive ligands is reduced. Exogenous
      administration of synthetic agonists of PPAR-gamma (pioglitazone and
      rosiglitazone) up-regulates PPAR-gamma-dependent genes, while inhibiting the
      activation of NF-kappaB and the secretion of proinflammatory cytokines
      (lipopolysaccharide-induced CXC chemokine, monocyte chemotactic protein-1,
      macrophage inflammatory protein-2, granulocyte colony-stimulating factor,
      keratinocyte chemoattractant) in response to lipopolysaccharide. PPAR-gamma
      agonists modulate NF-kappaB-dependent inflammation by up-regulating nuclear
      factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha, a
      negative regulator of NF-kappaB. Stimulation of PPAR-gamma in vivo
      (rosiglitazone) significantly attenuates biliary damage and inflammation in Cftr
      knockout mice exposed to a dextran sodium sulfate-induced portal endotoxemia.
      CONCLUSION: These studies unravel a novel function of PPAR-gamma in controlling
      biliary epithelium inflammation and suggest that impaired activation of PPAR
      gamma contributes to the chronic inflammatory state of CFTR-defective
      cholangiocytes.

PMID- 26199138
TI  - Syntagmatic and paradigmatic development of cochlear implanted children in
      comparison with normally hearing peers up to age 7.
AB  - OBJECTIVE: Grammatical development is shown to be delayed in CI children.
      However, the literature has focussed mainly on one aspect of grammatical
      development, either morphology or syntax, and on standard tests instead of
      spontaneous speech. The aim of the present study was to compare grammatical
      development in the spontaneous speech of Dutch-speaking children with cochlear
      implants and normally hearing peers. Both syntagmatic and paradigmatic
      development will be assessed and compared with each other. METHOD: Nine children
      with cochlear implants were followed yearly between ages 2 and 7. There was a
      cross-sectional control group of 10 normally hearing peers at each age. Syntactic
      development is measured by means of Mean Length of Utterance (MLU), morphological
      development by means of Mean Size of Paradigm (MSP). This last measure is
      relatively new in child language research. RESULTS: MLU and MSP of children with
      cochlear implants lag behind that of their normally hearing peers up to age 4 and
      up to age 6 respectively. By age 5, CI children catch up on MSP and by age 7 they
      caught up on MLU. CONCLUSION: Children with cochlear implants catch up with their
      normally hearing peers for both measures of syntax and morphology. However, it is
      shown that inflection is earlier age-appropriate than sentence length in CI
      children. Possible explanations for this difference in developmental pace are
      discussed.

PMID- 26199139
TI  - Utility of 3D Printing for Complex Distal Tibial Fractures and Malleolar Avulsion
      Fractures: Technical Tip.

PMID- 26199141
TI  - Gender: the state of being male or female.

PMID- 26199140
TI  - DOT1L cooperates with the c-Myc-p300 complex to epigenetically derepress CDH1
      transcription factors in breast cancer progression.
AB  - DOT1L has emerged as an anticancer target for MLL-associated leukaemias; however,
      its functional role in solid tumours is largely unknown. Here we identify that
      DOT1L cooperates with c-Myc and p300 acetyltransferase to epigenetically activate
      epithelial-mesenchymal transition (EMT) regulators in breast cancer progression.
      DOT1L recognizes SNAIL, ZEB1 and ZEB2 promoters via interacting with the c-Myc
      p300 complex and facilitates lysine-79 methylation and acetylation towards
      histone H3, leading to the dissociation of HDAC1 and DNMT1 in the regions. The
      upregulation of these EMT regulators by the DOT1L-c-Myc-p300 complex enhances EMT
      induced breast cancer stem cell (CSC)-like properties. Furthermore, in vivo
      orthotopic xenograft models show that DOT1L is required for malignant
      transformation of breast epithelial cells and breast tumour initiation and
      metastasis. Clinically, DOT1L expression is associated with poorer survival and
      aggressiveness of breast cancers. Collectively, we suggest that cooperative
      effect of DOT1L and c-Myc-p300 is critical for acquisition of aggressive
      phenotype of breast cancer by promoting EMT/CSC. 

PMID- 26199143
TI  - The acute testosterone, growth hormone, cortisol and interleukin-6 response to
      164-km road cycling in a hot environment.
AB  - This study investigated the acute endocrine responses to a 164-km road cycling
      event in a hot environment. Thirty-four male experienced cyclists (49.1 +/- 8.3
      years, 86.8 +/- 12.5 kg, 178.1 +/- 5.1 cm) participating in a 164-km road cycling
      event were recruited. Blood samples were collected within 0.3-2.0 h before the
      start (PRE: ~0500-0700 h) and immediately following the ride (POST). Samples were
      analysed for testosterone, growth hormone (GH), cortisol and interleukin-6 (IL
      6). The temperature and humidity during the event were 35.3 +/- 4.9 degrees C and
      47.2 +/- 14.0%, respectively. Based on the finishing time, results for the
      fastest (FAST, 305 +/- 10 min) and the slowest (SLOW, 467 +/- 31 min) quartiles
      were compared. At POST, testosterone concentration was significantly (P < 0.05)
      lower (PRE, 20.8 +/- 8.6; POST, 18.2 +/- 6.7 nmol . L(-1)), while GH (PRE, 0.3 +/
      0.1; POST, 2.3 +/- 0.3 ug . L(-1)), cortisol (PRE, 661 +/- 165; POST, 1073 +/-
      260 nmol . L(-1)) and IL-6 (PRE, 4.0 +/- 3.4; POST, 22.4 +/- 15.2 pg . mL(-1))
      concentrations were significantly higher than those at PRE. At POST, GH and
      cortisol were significantly higher for the FAST group than for the SLOW group
      (GH, 3.6 +/- 2.0 and 1.0 +/- 0.8 ug . L(-1); cortisol, 1187 +/- 209 and 867 +/-
      215 nmol . L(-1)). Participation in an ultra-endurance road cycling event in a
      hot environment induced significant acute changes in concentrations of
      circulating hormones, with a greater augmentation of GH and cortisol in those
      completing the ride fastest. 

PMID- 26199142
TI  - Overcoming Clinical Inertia: A Randomized Clinical Trial of a Telehealth Remote
      Monitoring Intervention Using Paired Glucose Testing in Adults With Type 2
      Diabetes.
AB  - BACKGROUND: Type 2 diabetes mellitus is a worldwide challenge. Practice
      guidelines promote structured self-monitoring of blood glucose (SMBG) for
      informing health care providers about glycemic control and providing patient
      feedback to increase knowledge, self-efficacy, and behavior change. Paired
      glucose testing-pairs of glucose results obtained before and after a meal or
      physical activity-is a method of structured SMBG. However, frequent access to
      glucose data to interpret values and recommend actions is challenging. A complete
      feedback loop-data collection and interpretation combined with feedback to modify
      treatment-has been associated with improved outcomes, yet there remains limited
      integration of SMBG feedback in diabetes management. Incorporating telehealth
      remote monitoring and asynchronous electronic health record (EHR) feedback from
      certified diabetes educators (CDEs)-specialists in glucose pattern management
      employ the complete feedback loop to improve outcomes. OBJECTIVE: The purpose of
      this study was to evaluate a telehealth remote monitoring intervention using
      paired glucose testing and asynchronous data analysis in adults with type 2
      diabetes. The primary aim was change in glycated hemoglobin (A(1c))-a measure of
      overall glucose management-between groups after 6 months. The secondary aims were
      change in self-reported Summary of Diabetes Self-Care Activities (SDSCA),
      Diabetes Empowerment Scale, and Diabetes Knowledge Test. METHODS: A 2-group
      randomized clinical trial was conducted comparing usual care to telehealth remote
      monitoring with paired glucose testing and asynchronous virtual visits.
      Participants were aged 30-70 years, not using insulin with A1c levels between
      7.5% and 10.9% (58-96 mmol/mol). The telehealth remote monitoring tablet computer
      transmitted glucose data and facilitated a complete feedback loop to educate
      participants, analyze actionable glucose data, and provide feedback. Data from
      paired glucose testing were analyzed asynchronously using computer-assisted
      pattern analysis and were shared with patients via the EHR weekly. CDEs called
      participants monthly to discuss paired glucose testing trends and treatment
      changes. Separate mixed-effects models were used to analyze data. RESULTS:
      Participants (N=90) were primarily white (64%, 56/87), mean age 58 (SD 11) years,
      mean body mass index 34.1 (SD 6.7) kg/m2, with diabetes for mean 8.2 (SD 5.4)
      years, and a mean A(1c) of 8.3% (SD 1.1; 67 mmol/mol). Both groups lowered A(1c)
      with an estimated average decrease of 0.70 percentage points in usual care group
      and 1.11 percentage points in the treatment group with a significant difference
      of 0.41 percentage points at 6 months (SE 0.08, t159=-2.87, P=.005). Change in
      medication (SE 0.21, t157=-3.37, P=.009) was significantly associated with lower
      A(1c) level. The treatment group significantly improved on the SDSCA subscales
      carbohydrate spacing (P=.04), monitoring glucose (P=.001), and foot care (P=.02).
      CONCLUSIONS: An eHealth model incorporating a complete feedback loop with
      telehealth remote monitoring and paired glucose testing with asynchronous data
      analysis significantly improved A(1c) levels compared to usual care. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01715649;
      https://www.clinicaltrials.gov/ct2/show/NCT01715649 (Archived by WebCite at
      http://www.webcitation.org/6ZinLl8D0).

PMID- 26199144
TI  - Oral Everolimus for Treatment of a Giant Left Ventricular Rhabdomyoma in a
      Neonate-Rapid Tumor Regression Documented by Real Time 3D Echocardiography.
AB  - The presented case reports on successful treatment with everolimus in a neonate
      with left ventricular giant rhabdomyoma. The authors used a different dosage
      regime compared to literature and documented rapid tumor regression by 3D
      echocardiography. 

PMID- 26199145
TI  - Ab initio-predicted micro-mechanical performance of refractory high-entropy
      alloys.
AB  - Recently developed high-entropy alloys (HEAs) consisting of multiple principal
      elements represent a new field of metallurgy and have demonstrated appealing
      properties for a wide range of applications. Using ab initio alloy theory, we
      reveal the alloying effect on the elastic properties and the ideal tensile
      strength (ITS) in the [001] direction of four body-centered cubic (bcc)
      refractory HEAs based on Zr, V, Ti, Nb, and Hf. We find that these HEAs show high
      elastic anisotropy and large positive Cauchy pressure, suggesting good extrinsic
      ductility. Starting from ZrNbHf, it is found that the ITS decreases with
      equimolar Ti addition. On the other hand, if both Ti and V are added to ZrNbHf,
      the ITS is enhanced by about 42%. An even more captivating effect is the ITS
      increase by about 170%, if Ti and V are substituted for Hf. The alloying effect
      on the ITS is explained by the d-band filling. An intrinsic brittle-to-ductile
      transition is found in terms of the failure mode under uniaxial tension. These
      investigations suggest that intrinsically ductile HEAs with high ideal strength
      can be achieved by controlling the proportion of group four elements to group
      five elements. 

PMID- 26199146
TI  - Early development and allometric growth patterns of the grumata (Prochilodus
      vimboides Kner, 1859).
AB  - The objective of this study was to characterize the early development and
      allometric growth of the grumata (Prochilodus vimboides). We describe a sample of
      266 eggs and larvae obtained through induced spawning. The eggs were spherical
      (mean 3.7 mm diameter), exhibited a yellow yolk and were non-adhesive and pelagic
      after fertilization and hydration. The time elapsed between the early cleavage
      and post-flexion stages was considered short (328 hours, 8054 hour-degrees) in
      regard to the development times of other Neotropical rheophilic species, but time
      to hatching was considerably longer than in other Prochilodus species. The most
      notable anatomical changes were observed between the end of the yolk larval stage
      and the beginning of the pre-flexion stage, when the larvae displayed directed
      swimming and the digestive system became functional, enabling the transition from
      endogenous to exogenous feeding. After hatching, the larvae grew from 6.04 to
      15.15 mm in total length average. Two growth phases were observed at this stage:
      a non-linear asymptotic curve in yolk-sac larvae, and a linear constant-rate
      growth phase after exogenous feeding started. Allometric growth related to
      standard length was positive for head length, negative for eye diameter, and
      switched between phases from negative to positive in body depth and head height.
      Morphological development and allometric growth in different larval phases impose
      drastic anatomical and physiological changes that are synchronic with habitat
      changes and the flood cycles during the reproductive period. 

PMID- 26199147
TI  - The influence of context on the effectiveness of hospital quality improvement
      strategies: a review of systematic reviews.
AB  - BACKGROUND: It is now widely accepted that the mixed effect and success rates of
      strategies to improve quality and safety in health care are in part due to the
      different contexts in which the interventions are planned and implemented. The
      objectives of this study were to (i) describe the reporting of contextual factors
      in the literature on the effectiveness of quality improvement strategies, (ii)
      assess the relationship between effectiveness and contextual factors, and (iii)
      analyse the importance of contextual factors. METHODS: We conducted an umbrella
      review of systematic reviews searching the following databases: PubMed, Cochrane
      Database of Systematic Reviews, Embase and CINAHL. The search focused on quality
      improvement strategies included in the Cochrane Effective Practice and
      Organisation of Care Group taxonomy. We extracted data on quality improvement
      effectiveness and context factors. The latter were categorized according to the
      Model for Understanding Success in Quality tool. RESULTS: We included 56
      systematic reviews in this study of which only 35 described contextual factors
      related with the effectiveness of quality improvement interventions. The most
      frequently reported contextual factors were: quality improvement team (n = 12),
      quality improvement support and capacity (n = 11), organization (n = 9), micro
      system (n = 8), and external environment (n = 4). Overall, context factors were
      poorly reported. Where they were reported, they seem to explain differences in
      quality improvement effectiveness; however, publication bias may contribute to
      the observed differences. CONCLUSIONS: Contextual factors may influence the
      effectiveness of quality improvement interventions, in particular at the level of
      the clinical micro-system. Future research on the implementation and
      effectiveness of quality improvement interventions should emphasize formative
      evaluation to elicit information on context factors and report on them in a more
      systematic way in order to better appreciate their relative importance.

PMID- 26199150
TI  - Chemical composition and antioxidant activities of the essential oil from Nandina
      domestica fruits.
AB  - The chemical composition and antioxidant activities of the essential oil from
      Nandina domestica fruits were studied for the first time. Twenty-two compounds,
      representing 82.79% of the oil, were identified from the oil. The major compounds
      were 3-hexen-1-ol (12.9%), linalool (12.3%), 2-methoxy-4-vinylphenol (9.9%),
      oleic acid (8.0%), furfural (5.8%) and 2,6-di-tert-butyl-4-methylphenol (5.7%).
      The antioxidant activities of the oil were evaluated using reducing power, metal
      chelating ability and scavenging capacity against 1,1-diphenyl-2-picrylhydrazyl
      (DPPH), 2,2'-azinobis-3-ethylbenzthiazoline-6-sulfonate (ABTS) and superoxide
      anion free radical. The oil exhibited significant antioxidant activities. 

PMID- 26199149
TI  - Postoperative Effects of Thiopurines in Patients with Intestinal Behcet's
      Disease.
AB  - BACKGROUND: No studies have heretofore specifically focused on the efficacy of
      postoperative thiopurine therapy in intestinal Behcet's disease (BD). We
      conducted this study to assess the clinical effects of postoperative thiopurines
      in patients with intestinal BD. METHODS: We reviewed the medical records of all
      patients with intestinal BD who had undergone bowel resection surgery in a single
      tertiary academic medical center between 1991 and 2013. The cumulative
      probabilities of clinical recurrence were calculated using the Kaplan-Meier
      method, and predictive factors for recurrence were assessed by multivariate
      analysis. RESULTS: A total of 77 patients with intestinal BD received 5-ASA (n =
      50, 64.9%) or thiopurine (n = 27, 35.1%) therapy after surgery at our center. The
      postoperative recurrence rate was lower in patients who received postoperative
      thiopurines (P = 0.050). The hazard ratio for recurrence was 0.636 (95%
      confidence interval 0.130-1.016, P = 0.053) for postoperative thiopurine use
      compared with postoperative 5-ASA. However, the rates of re-operation, re
      admission, and death were not significantly different between the 5-ASA and
      thiopurine groups. CONCLUSIONS: Thiopurine therapy after surgery exhibited a
      modest effect in preventing recurrence in intestinal BD patients. More patients,
      long-term follow-up, and a randomized controlled design are necessary to validate
      the effectiveness of postoperative thiopurines in patients with this disease.

PMID- 26199148
TI  - G protein-gated inwardly rectifying potassium channel subunits 1 and 2 are down
      regulated in rat dorsal root ganglion neurons and spinal cord after peripheral
      axotomy.
AB  - BACKGROUND: Increased nociceptive neuronal excitability underlies chronic pain
      conditions. Various ion channels, including sodium, calcium and potassium
      channels have pivotal roles in the control of neuronal excitability. The members
      of the family of G protein-gated inwardly rectifying potassium (GIRK) channels,
      GIRK1-4, have been implicated in modulating excitability. Here, we investigated
      the expression and distribution of GIRK1 and GIRK2 in normal and injured dorsal
      root ganglia (DRGs) and spinal cord of rats. RESULTS: We found that ~70% of the
      DRG neurons expressed GIRK1, while only <10% expressed GIRK2. The neurochemical
      profiles of GIRK1- and GIRK2-immunoreactive neurons were characterized using the
      neuronal markers calcitonin gene-related peptide, isolectin-B4 and neurofilament
      200, and the calcium-binding proteins calbindin D28k, calretinin, parvalbumin and
      secretagogin. Both GIRK subunits were expressed in DRG neurons with nociceptive
      characteristics. However, while GIRK1 was widely expressed in several sensory
      neuronal subtypes, GIRK2 was detected mainly in a group of small C-fiber neurons.
      In the spinal dorsal horn, GIRK1- and -2-positive cell bodies and processes were
      mainly observed in lamina II, but also in superficial and deeper layers. Abundant
      GIRK1-, but not GIRK2-like immunoreactivity, was found in the ventral horn
      (laminae VI-X). Fourteen days after axotomy, GIRK1 and GIRK2 were down-regulated
      in DRG neurons at the mRNA and protein levels. Both after axotomy and rhizotomy
      there was a reduction of GIRK1- and -2-positive processes in the dorsal horn,
      suggesting a presynaptic localization of these potassium channels. Furthermore,
      nerve ligation caused accumulation of both subunits on both sides of the lesion,
      providing evidence for anterograde and retrograde fast axonal transport.
      CONCLUSIONS: Our data support the hypothesis that reduced GIRK function is
      associated with increased neuronal excitability and causes sensory disturbances
      in post-injury conditions, including neuropathic pain.

PMID- 26199151
TI  - Prostatic Arterial Embolization vs Open Prostatectomy: A 1-Year Matched-pair
      Analysis of Functional Outcomes and Morbidities.
AB  - OBJECTIVE: To evaluate 1-year surgical and functional results and morbidities of
      prostatic artery embolization (PAE) vs open prostatectomy (OP). PATIENTS AND
      METHODS: We undertook 1:1 matched-pair analysis (International Prostate Symptom
      Score [IPSS], peak flow [PF], postvoid residual [PVR], and prostate volume) of
      287 consecutive patients treated for benign prostatic obstruction, including 80
      OP and 80 PAE. Inclusion criteria were as follows: lower urinary tract symptoms
      or benign prostatic obstruction, IPSS >=12, prostate-specific antigen (PSA) <4
      ng/mL, or PSA between 4 and 10 ng/mL but negative prostate biopsy, total prostate
      volume >80 cm(3), and PF <15 mL/s. Follow-up was performed at 1 month, 6 months,
      and 1 year at clinic. Primary end points of the study were the comparison
      regarding IPSS, International Index of Erectile Function-5, PF, PVR, and IPSS
      quality of life (IPSS-QoL) after 1 year of follow-up. RESULTS: Regarding primary
      end points, OP group had lower IPSS (4.31 vs 10.40; P <.05), 1-year PVR (6.15 vs
      18.38; P <.05), 1-year PSA (1.33 vs 2.12; P <.05), IPSS-QoL (0.73 vs 2.78; P
      <.05), International Index of Erectile Function-5 (10.88 vs 15.13; P <.05), and
      greater PF (23.82 vs 16.89; P <.01). The matched-pair comparison showed higher
      value of postoperative hemoglobin level (mg/dL) and shorter hospitalization
      (days) and catheterization (days) for PAE group. At the multivariate logistic
      regression, PAE was associated with persistent symptoms (IPSS >=8; odds ratio,
      2.67; 95% confidence interval [CI], 0.96-7.4; P <.01) and persistent PF <=15 mL/s
      (odds ratio, 4.95; 95% confidence interval, 1.73-14.15; P <.05) after 1 year.
      CONCLUSION: PAE could be considered a feasible minimally invasive technique but
      failed to demonstrate superiority to OP because of the increased risk of
      persistent symptoms and low PF after 1 year.

PMID- 26199152
TI  - Urethral Calculi in a 7-Year-old Boy Presenting as a Large Scrotal Mass After
      Surgery of Exstrophy-epispadias Repair.
AB  - Urethral calculi are extremely rare in pediatric population and are usually
      presented with dysuria, hematuria, lower urinary tract obstruction, and rarely as
      a scrotal mass. We here report a giant primary urethral stone presenting as a
      scrotal mass that developed in the penile urethra resulting from a postsurgical
      complication of exstrophy-epispadias repair. A 7-year-old boy was admitted with
      the complaint of scrotal mass and dysuria. Computerized tomography confirmed
      giant urethral stone impacted to diverticulum of urethra. Cystoscopy revealed a
      nonobstructed stone in the urethra related to a posterior diverticulum. After
      scrotal incision, stone was removed with open diverticulectomy. 

PMID- 26199153
TI  - Editorial Comment.

PMID- 26199154
TI  - Reply: To PMID 26199153.

PMID- 26199155
TI  - Ureteropelvic Junction Obstruction by a Long Intraluminal Polyp and a Concurrent
      Crossing Vein in a Symptomatic 8-Year-old Child.
AB  - Ureteropelvic junction obstruction due to intrinsic causes is often diagnosed
      antenatally during routine ultrasonography. Cases of extrinsic obstruction often
      present later and symptomatically, during childhood. We describe the rare case of
      an 8-year-old boy with a 2-day history of severe left flank pain, no fevers, and
      Society of Fetal Urology grade 3 hydronephrosis on ultrasonography. Laparoscopic
      dismembered pyeloplasty revealed a left ureteropelvic junction obstruction
      secondary to a large fibroepithelial polyp in the proximal ureter with a
      concomitant anterior crossing vein. We also provide a focused review of the
      pertinent published literature. 

PMID- 26199156
TI  - Editorial Comment.

PMID- 26199157
TI  - Reply: To PMID 26199156.

PMID- 26199158
TI  - Patient-Reported Sexual Function After Staged Penile Urethroplasty.
AB  - OBJECTIVE: To evaluate sexual function after staged penile urethroplasty with
      oral mucosal graft (OMG). METHODS: We identified men with completed staged penile
      urethroplasty with OMG from the Trauma and Urologic Reconstruction Network of
      Surgeons database between January 1, 2010 and May 1, 2014. Our primary outcome
      was change in total Sexual Health Inventory for Men (SHIM) and total Male Sexual
      Health Questionnaire Ejaculatory Domain (MSHQ-EjD) Short Form at baseline vs
      after the second stage of the procedure. Second, we assessed subjective changes
      in penile curvature, length, and sensation. RESULTS: Thirty-three patients were
      included with a mean age of 45 years and mean body mass index of 27.6 kg/m(2).
      Urethral strictures arose from failed hypospadias repair in 52% and lichen
      sclerosus in 27%. Fifty-two percent of patients reported a previous
      urethroplasty. The median follow-up time between the second stage procedure and
      postoperative questionnaires was 6.3 months (interquartile range: 3.5-13.3).
      There was no significant change in the total SHIM (Delta0.64, 95% confidence
      interval [CI]: -3.00~1.72) and MSHQ-EjD (Delta1.55, 95% CI: -1.53~4.63) scores
      preoperatively vs postoperatively. In addition, 32% reported improved and 52% no
      change in satisfaction with sexual intercourse (SHIM Q5). Forty percent of
      patients reported reduced and 45% no change in bother with ejaculation after
      surgery (MSHQ-EjD Q4). Men reported new penile curvature (23%), loss of penile
      length (55%), and altered penile sensitivity (45%) after surgery. CONCLUSION:
      Patients undergoing staged penile urethroplasty with OMG are likely to have
      minimal changes in erectile and ejaculatory function postoperatively, although
      many may experience new penile curvature, reduced penile length, and/or reduced
      penile sensitivity.

PMID- 26199160
TI  - Reply: To PMID 26199159.

PMID- 26199159
TI  - Effectiveness of Transobturator Tape Procedure in Obese and Severely Obese Women:
      3-Year Follow-up.
AB  - OBJECTIVE: To assess the efficacy and safety of transobturator tape (TOT) for the
      treatment of stress urinary incontinence in severely obese and obese women.
      METHODS: We retrospectively reviewed the women who underwent a TOT procedure at 2
      institutions between March 2005 and March 2013. The patients were divided into 3
      groups according to the World Health Organization body mass index (BMI) values:
      normal weight group (BMI <25 kg/m(2); group 1), obese group (BMI = 30-34 kg/m(2);
      group 2), and severely obese group (BMI >=35 kg/m(2); group 3). Overweight women
      (BMI = 25-29 kg/m(2)) were omitted. Patients filled in the International
      Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) preoperatively
      and at the postoperative follow-up visits. The severity of urinary incontinence
      was classified by ICIQ-SF: slight (1-5), moderate (6-12), severe (13-18), and
      very severe (19-21). Patient satisfaction was assessed using a visual analog
      scale. Subjective improvement was defined as an ICIQ-SF score <=12 and
      satisfaction with surgery (visual analog scale score >=80). RESULTS: A total 470
      women met the requirements for inclusion. There were 153 women in group 1, 72
      women in group 2, and 32 women in group 3. Mean follow-up period was at least 12
      months in all the groups. The difference between the groups according to mean
      operative time was significant (P <.001). The objective cure, subjective success
      (cured and improved), patient satisfaction rates, and complications were similar
      between the groups. CONCLUSION: Obesity and severe obesity do not seem to be risk
      factors for the failure of TOT procedure. However, postoperative urgency urinary
      incontinence rate was higher in severely obese women, and more women showed
      improvement instead of cure among severely obese women.

PMID- 26199161
TI  - Editorial Comment.

PMID- 26199163
TI  - Pediatric Priapism Secondary to Psychotherapeutic Medications.
AB  - With the increased application of many different drug classes for the treatment
      of psychiatric conditions in children, the incidence of priapism has also
      increased. Priapism of pharmacotherapeutic etiology in the pediatric population
      is a complex and poorly understood entity that continues to present new
      management challenges for clinicians. We present 2 cases of pediatric priapism
      thought to be secondary to the use of pharmacotherapeutic agents. In the first
      case, sertraline, an antidepressant, and in the second case, atomoxetine, a
      nonstimulant medication, are implicated as the most likely causative agents. Both
      medications have a growing association with priapism in the literature. 

PMID- 26199162
TI  - Clinical Outcome of a Prospective Case Series of Patients With Ketamine Cystitis
      Who Underwent Standardized Treatment Protocol.
AB  - OBJECTIVE: To assess the outcome of a prospective cohort of patients with
      ketamine-associated uropathy after standardized treatment. METHODS: This is a
      prospective case series of patients with ketamine-related urologic problems.
      Management for the patients includes a 4-tier approach, namely anti-inflammatory
      or anti-cholinergic drugs, opioid analgesics or pregabalin, intravesical
      hyaluronic acid, and finally, surgical intervention including hydrodistension and
      augmentation cystoplasty. Outcome was assessed with functional bladder capacity,
      pelvic pain and urgency or frequency (PUF) symptom scale, and the EuroQol visual
      analog scale. RESULTS: Between December 2011 and June 2014, 463 patients
      presented with ketamine-associated uropathy. All were managed by the same
      standardized protocol. Among these patients, 319 patients came back for follow-up
      assessment. Overall mean follow-up duration was 10.7 +/- 8.5 months. For those
      patients who received first-line treatment (290 patients), there was a
      significant improvement in PUF scores, the EuroQol visual analog scale, and
      functional bladder capacity. Both abstinence from ketamine usage and the amount
      of ketamine consumed were factors predicting the improvement of PUF scores. For
      those patients who required second-line oral therapy (62 patients), 42 patients
      (67.7%) reported improvement in symptoms. Eight patients have completed
      intravesical therapy. There was a significant improvement in voided volume for
      the patients after treatment. CONCLUSION: The study demonstrated the efficacy of
      managing ketamine-associated uropathy using a 4-tier approach. Both anti
      inflammatory drugs and analgesics could effectively alleviate symptoms. Being
      abstinent from ketamine abuse and the amount of ketamine consumed have bearings
      on treatment response.

PMID- 26199164
TI  - Trends in Metastatic Kidney Cancer Survival From the Cytokine to the Targeted
      Therapy Era.
AB  - OBJECTIVE: To evaluate population-based survival trends, compared to optimistic
      trial benchmarks, in metastatic renal cell carcinoma (mRCC). Advances in medical
      therapy for mRCC may be associated with survival improvements. Yet, targeted
      therapy trial results focus on patients with favorable-risk mRCC and may not be
      well disseminated at the population level. METHODS: Surveillance, Epidemiology,
      and End Results identified adult mRCC patients diagnosed between 1990 and 2009.
      Survival was analyzed by treatment era (cytokine, 1990-2005; targeted therapy,
      2006-2009) and stratified by histology. Multivariate Cox regression identified
      factors independently associated with overall survival. RESULTS: We identified
      14,521 eligible patients. For clear cell mRCC (N = 4149), median survival
      improved from 11 to 14 months before and after targeted therapy (P <.001). For
      RCC with sarcomatoid features (N = 608) and RCC not otherwise specified (N =
      8860), survival did not change (median survival 4 months for both). For non-clear
      cell subtypes (N = 904), median survival improved from 7 to 9 months (P = .008).
      On multivariate analysis, factors associated with increased overall survival were
      as follows: treatment in the targeted era (hazard ratio [HR], 0.87; 95%
      confidence interval [CI], 0.84-0.91), clear cell histology (HR, 0.76; 95% CI,
      0.73-0.80), and receipt of surgery (HR, 0.43; 95% CI, 0.41-0.46). CONCLUSION:
      Population-based mRCC median survival improved but to a lesser degree than that
      reported in clinical trials. This represents opportunity for quality improvement
      in histologically guided care, use of cytoreductive nephrectomy, and development
      of strategies for trial-ineligible, poor-risk patients.

PMID- 26199165
TI  - Treatment With Metformin Improves Erectile Dysfunction in a Murine Model of
      Obesity Associated With Insulin Resistance.
AB  - OBJECTIVE: To evaluate the effects of treatment with metformin on a murine model
      of obesity-associated erectile dysfunction. MATERIAL AND METHODS: C57BL/6 male
      mice were fed for 10 weeks with standard chow or high-fat diet. Lean and obese
      mice were treated with the insulin sensitizer metformin (300 mg/kg/day, 2 weeks).
      Intracavernosal pressure (ICP) and in vitro corpus cavernosum (CC) relaxations to
      both acetylcholine and electrical field stimulation, as well as phenylephrine
      induced contractions, were obtained. Levels of cyclic guanosine monophosphate in
      CC were detected by enzyme immunoassay. RESULTS: High-fat-fed mice exhibited
      higher body weight and insulin resistance. Cavernous nerve stimulation caused
      frequency-dependent ICP increases, which were significantly lower in obese
      compared with lean mice (P <.05). Two-week therapy with metformin reversed the
      decreased ICP in obese group. The maximal response to acetylcholine in CC was 35%
      lower (P <.05) in the obese compared to the lean group, which were restored by
      metformin treatment. Likewise, the impaired electrical field stimulation-induced
      CC relaxations in obese mice were also partly restored by metformin. Contractile
      responses to phenylephrine were significantly greater (P <.05) in obese compared
      to lean mice, which were fully restored by metformin. Basal and stimulated cyclic
      guanosine monophosphate productions in the erectile tissues were significantly
      lower (P <.05) in the obese group, an effect fully restored by metformin.
      CONCLUSION: Treatment with metformin restored the erectile function in obese
      mice, through improvement of in vitro endothelial and nitrergic cavernosal
      relaxations. Therefore, use of metformin may be a good pharmacologic approach to
      treat insulin resistance-associated erectile dysfunction.

PMID- 26199166
TI  - Association of Free Testosterone With Hypogonadal Symptoms in Men With Near
      normal Total Testosterone Levels.
AB  - OBJECTIVE: To investigate the association between hypogonadal symptoms and free
      testosterone (FT) levels in men with near-normal total testosterone (T) levels
      (250-350 ng/dL) and to determine whether a discriminatory threshold for FT exists
      below which hypogonadal symptoms become more prevalent. METHODS: We reviewed the
      charts of 3167 men who presented to an outpatient men's health clinic. Two
      hundred thirty-one men had symptoms of "low testosterone" and serum testosterone
      levels between 250 and 350 ng/dL. We evaluated hypogonadal symptoms using the
      Androgen Deficiency in the Adult Male (ADAM) and quantitative ADAM (qADAM)
      questionnaires. Serum levels of T and sex hormone-binding globulin were collected
      on the same day that men completed their questionnaires. We used linear
      regression to determine whether a threshold of FT exists for hypogonadal
      symptoms. We performed univariate and multivariable analyses to evaluate factors
      that predicted a low FT level. RESULTS: The median age was 43.5 years, and the
      median testosterone and FT levels were 303 ng/dL and 6.3 ng/dL, respectively.
      Prevalence and severity of hypogonadal symptoms (ADAM and qADAM) were similar
      between men with low (<6.4 ng/mL) and normal FT levels. There was an association
      between age and 3 of the 10 hypogonadal symptoms (decreased enjoyment in life,
      sadness, and deterioration of work performance) with a low FT on a univariate
      analysis. Only younger age was positively associated with FT on multivariable
      analysis. CONCLUSION: We did not observe a relationship between hypogonadal
      symptoms and FT in men with near-normal testosterone levels. Symptom-specific FT
      thresholds could not be defined, as age remains an important confounder.

PMID- 26199167
TI  - High-risk Oncogenic Human Papilloma Virus Infection of the Foreskin and
      Microbiology of Smegma in Prepubertal Boys.
AB  - OBJECTIVE: To evaluate the prevalence and genotypes of human papillomavirus (HPV)
      infection and microbiological status of the foreskin in asymptomatic prepubertal
      boys. METHODS: A total of 100 prepubertal healthy boys who underwent a standard
      circumcision procedure were included in the study. High-risk HPV status was
      determined by real-time polymerase chain reaction for the genotypes 16, 18, 31,
      33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68. The swabs were immediately sent
      to microbiology laboratory for culture and sensitivity tests. RESULTS: The median
      age at the time of surgery was 5.7 years (range, 2 months-9 years). High-risk HPV
      was detected in 9 foreskins (9%). Positive samples showed are HPV16 (n = 3), 31
      (n = 2), 39 (n = 3), and 51 (n = 1). There were a total of 72 organism isolates:
      54 gram-positive (75%) and 17 gram-negative (23.6%) bacteria and 1 (1.4%)
      Candida. The most commonly isolated gram-negative bacterium was Escherichia coli
      (41.2%), whereas the commonly isolated gram-positive bacterium was Enterecoccus
      sp. (57.4%). CONCLUSION: Our results showed that subclinical high-risk HPV
      infections are found in the foreskin, which could be a reservoir for HPV
      associated diseases, and smegma seems not to be a risk factor for drug-resistant
      infection in children.

PMID- 26199168
TI  - Self-report and Clinical Response to Peyronie's Disease Treatment: Peyronie's
      Disease Questionnaire Results From 2 Large Double-Blind, Randomized, Placebo
      Controlled Phase 3 Studies.
AB  - OBJECTIVE: To evaluate the clinical usefulness of the Peyronie's Disease
      Questionnaire (PDQ). The relationship between subject-reported changes in PDQ
      psychosexual symptoms and clinical response to Peyronie's disease (PD) treatment
      was examined. MATERIALS AND METHODS: Combined data from the collagenase
      Clostridium histolyticum phase 3 study program, IMPRESS (Investigation for
      Maximal Peyronie's Reduction Efficacy and Safety Studies) I and II, were
      examined. Changes in the PDQ PD symptom bother, psychological and physical
      symptoms, and penile pain were examined relative to changes in the penile
      curvature deformity, including penile curvature absolute mean and percent change.
      PDQ changes relative to sexual function, including International Index of
      Erectile Function overall satisfaction and erectile function domains, and
      treatment responder status, including global assessment of PD and composite
      responder status, were also assessed. Individual PDQ questions were examined to
      provide a clinical perspective on the change in psychosexual symptoms experienced
      by men with PD during treatment. RESULTS: Improvement in PDQ PD symptom bother
      and psychological and physical symptoms was significantly correlated with
      clinical improvement in penile curvature deformity (P <=.0008) and sexual
      function (P <.0001). Significant differences in PD symptom bother and
      psychological and physical symptoms improvement were found between treatment
      responders vs nonresponders (P <.02). PDQ penile pain improvement among subjects
      reporting baseline pain >=4 was significantly correlated with clinical
      improvement in sexual function (P <=.0004) and was found to be greater in
      treatment responders vs nonresponders (P = .003). CONCLUSION: The utility of the
      PDQ for monitoring PD-specific psychosexual symptom severity, progression, and
      treatment response, both clinically and in trials of men with PD, was supported.

PMID- 26199169
TI  - Editorial Comment.

PMID- 26199170
TI  - Reply: To PMID 26199169.

PMID- 26199171
TI  - Residual Parenchymal Volume, Not Warm Ischemia Time, Predicts Ultimate Renal
      Functional Outcomes in Patients Undergoing Partial Nephrectomy.
AB  - OBJECTIVE: To examine relative contributions of functional parenchymal
      preservation and renal ischemia following nephron-sparing surgery (NSS). While
      residual functional parenchymal volume (FPV) is proposed as the key factor in
      predicting functional outcomes following NSS, efforts to curtail ischemia time
      continue to add technical complexity to partial nephrectomy. METHODS: Our kidney
      cancer database was queried for patients who underwent NSS with warm ischemia
      time (WIT). Patients with cross-sectional imaging for FPV calculation were
      included. Cylindrical volume approximation methodology was used to calculate FPV,
      accounting for the volume of tumor's endophytic component. Percent estimated
      glomerular filtration rate (eGFR) preservation, perioperatively and at 6 months,
      was the outcome metric. Spearman correlation and linear regression analyses were
      used to evaluate associations of WIT and %FPV preservation with renal function
      preservation. RESULTS: Of the 179 patients included, median preoperative eGFR was
      88.4 (9.5% chronic kidney disease III or IV), tumor size was 2.7 cm
      (interquartile range [IQR] 2.0-3.6 cm), and R.E.N.A.L. nephrometry was low in
      34%, intermediate in 57%, and high in 9%. Median WIT was 30 minutes (IQR 24-36),
      resulting in 97.4% FPV preservation. Median postoperative eGFR at 6.4 months was
      80.5 (19.1% chronic kidney disease III or IV), a median of 93.1% eGFR
      preservation (IQR 85.1-101.7). At discharge, WIT (P <.001), not %FPV (P = .112),
      was associated with %eGFR preservation. However, 6 months following surgery, on
      multivariable analysis, both preoperative eGFR (linear regression coefficient = 
      0.208, P = .006) and %FPV preservation (linear regression coefficient = 0.491, P
      = .001), but not WIT (P = .946), demonstrated statistically significant
      association with %eGFR preservation. CONCLUSION: Residual FPV, and not WIT,
      appears to be the main predictor of ultimate renal function following NSS.

PMID- 26199172
TI  - Evaluation of Intravesical Prostatic Protrusion as a Predictor of Dutasteride
      Resistant Lower Urinary Tract Symptoms/Benign Prostatic Enlargement With a High
      Likelihood of Surgical Intervention.
AB  - OBJECTIVE: To investigate factors predicting that combination therapy would be
      insufficient in terms of efficacy, necessitating conversion to surgical
      intervention, in patients with lower urinary tract symptoms and/or benign
      prostatic enlargement. MATERIALS AND METHODS: In total, 218 patients given
      combination therapy for 6 months or more were enrolled in our study. Candidate
      factors for surgical intervention before dutasteride administration were
      statistically analyzed. We also examined the proportion of stromal components in
      resected specimens of the intravesical prostatic protrusion (IPP) portion using
      the point-counting technique according to IPP grades. RESULTS: Combination
      therapy was effective and was thus continued in 172 patients, whereas 46 required
      surgical intervention. The comparison between these two groups, by multivariate
      analysis, revealed significant differences in IPP and total International
      Prostate Symptom Score (IPSS). IPP (odds ratio 1.133, P <.001) was the strongest
      independent factor predicting conversion to surgical intervention. Receiver
      operating characteristic analysis identified the optimal cutoff value of IPP to
      be 8 mm (area under the curve: 0.9). This value yielded a sensitivity of 91% and
      a specificity of 72%. In addition, the mean proportion of stromal components in
      resected specimens of IPP according to IPP grades was grade I: 96.7%, grade II:
      57.8%, and grade III: 21.4% (P <.001 for all), respectively. CONCLUSION: Our
      results suggest that in lower urinary tract symptoms and/or benign prostatic
      enlargement associated with severe IPP, combination therapy might have
      insufficient efficacy due to a low proportion of stromal components,
      necessitating conversion to surgical intervention.

PMID- 26199174
TI  - Recurrent alterations of TNFAIP3 (A20) in T-cell large granular lymphocytic
      leukemia.
AB  - The pathogenesis of T-cell large granular lymphocytic leukemia (T-LGL) is poorly
      understood, as STAT3 mutations are the only known frequent genetic lesions. Here,
      we identified non-synonymous alterations in the TNFAIP3 tumor suppressor gene in
      3 of 39 T-LGL. In two cases these were somatic mutations, in one case the somatic
      origin was likely. A further case harbored a SNP that is a known risk allele for
      autoimmune diseases and B cell lymphomas. Thus, TNFAIP3 mutations represent
      recurrent genetic lesions in T-LGL that affect about 8% of cases, likely
      contributing to deregulated NF-kappaB activity in this leukemia. 

PMID- 26199175
TI  - Lymph node counts are valid indicators of the quality of surgical care in bladder
      cancer: a population-based study.
AB  - OBJECTIVE: To describe lymph node counts in routine clinical practice and
      evaluate their association with outcomes to explore its utility as a quality
      indicator. METHODS AND MATERIALS: Electronic records of treatment and surgical
      pathology reports were linked with the population-based Ontario Cancer Registry
      to identify all patients who underwent cystectomy between 1994 and 2008. Temporal
      trends were described over 3 periods: 1994 to 1998, 1999 to 2000, and 2004 to
      2008. Multivariate generalized linear regression analysis was used to determine
      the factors associated with the use of pelvic lymph node dissection (PLND). A Cox
      proportional hazards regression model was used to explore the associations
      between PLND and survival. RESULTS: The study population included 2,802 patients.
      Use of PLND (50%, 62%, and 85%, correspondingly), median node yield (5, 6, and 9,
      correspondingly), and node density (56%, 50%, and 39%, correspondingly) all
      improved over the study periods, 1994 to 1998, 1999 to 2000, and 2004 to 2008
      (P<0.001). In multivariate analysis, factors associated with not having PLND
      include advanced age, female sex, lower socioeconomic status, low surgeon volume,
      and partial cystectomy. In adjusted analyses, patients who did not receive a PLND
      had inferior overall (hazard ratio = 1.26, 95% CI: 1.15-1.38) and cancer-specific
      (hazard ratio = 1.23, 95% CI: 1.11-1.36) survival. Node yield, as well as
      density, was also associated with long-term survival. CONCLUSIONS: There is
      significant variation in use and quality of PLND at cystectomy in routine
      practice. Node counts are independently associated with long-term survival, and
      this association is persistent despite adjustment for provider-related variables.
      These results suggest that lymph node counts are a valid quality indicator of
      surgical care of muscle-invasive bladder cancer.

PMID- 26199173
TI  - Bryostatin activates HIV-1 latent expression in human astrocytes through a PKC
      and NF-KB-dependent mechanism.
AB  - Multiple studies have shown that HIV-1 patients may develop virus reservoirs that
      impede eradication; these reservoirs include the central nervous system (CNS).
      Despite an undetectable viral load in patients treated with potent
      antiretrovirals, current therapy is unable to purge the virus from these latent
      reservoirs. To broaden the inhibitory range and effectiveness of current
      antiretrovirals, the potential of bryostatin was investigated as a latent HIV-1
      activator. We used primary astrocytes, NHA cells, and astrocytoma cells U-87.
      Infected cells with HIV-1(NL4.3) were treated with bryostatin alone or in
      combination with different inhibitors. HIV-1 production was quantified by using
      ELISA. Transcriptional activity was measured using luciferase reporter gene
      assays by using lipofectin. We performed cotransfection experiments of the LTR
      promoter with the active NF-kappaB member p65/relA. To confirm the NF-kappaB
      role, Western blot and confocal microscopy were performed. Bryostatin reactivates
      latent viral infection in the NHA and U87 cells via activation of protein kinase
      C (PKC)-alpha and -delta, because the PKC inhibitors rottlerin and GF109203X
      abrogated the bryostatin effect. No alteration in cell proliferation was found.
      Moreover, bryostatin strongly stimulated LTR transcription by activating the
      transcription factor NF-kappaB. Bryostatin could be a beneficial adjunct to the
      treatment of HIV-1 brain infection.

PMID- 26199177
TI  - Highlights of topic "Pancreatic neuroendocrine tumors update".

PMID- 26199176
TI  - Outcomes of squamous histology in bladder cancer: a population-based study.
AB  - OBJECTIVES: Squamous cell carcinoma (SCC) of the bladder is an uncommon form of
      bladder cancer. Using a large population-based sample we sought to describe the
      outcomes of patients with squamous histology and to define the factors that
      influence prognosis in these patients. METHODS: All incident cases of bladder
      cancer in Ontario undergoing cystectomy from 1994 to 2008 were identified.
      Electronic treatment records and detailed pathologic information were linked to
      the study data set. Patients were divided into 3 cohorts: pure SCC, urothelial
      carcinoma (UC) with squamous differentiation (UCSD), and pure UC. Cox modeling
      was performed to evaluate factors associated with overall survival (OS) and
      cancer-specific survival (CSS). RESULTS: There were identified 178, 325, and
      2,884 cases of SCC, UCSD, and UC, respectively. The unadjusted 5-year OS for
      these groups were 33%, 28%, and 34%, respectively. Patients had higher rates of
      T3/4 disease with SCC (72%) and UCSD (73%) than those with UC (61%, P<0.001).
      There was no difference in node positivity among groups (20%, 27%, and 25%, P =
      0.519). After adjusting for covariates, SCC did not portend a worse survival, at
      5 years. However, SCC did result in a more rapid disease trajectory, with
      survival curves of SCC and UC crossing at the 5-year mark. Adjusted CSS/OS of
      UCSD was also not significantly different from UC. Among those patients with SCC,
      factors associated with CSS included age>70 (hazard ratio [HR] = 1.96, 95% CI:
      1.16-3.30), T category>=3 (HR = 2.09, 95% CI: 1.24-3.50), N positive disease (HR
      = 2.59, 95% CI: 1.55-4.32), lymphovascular invasion (HR = 1.98, 95% CI: 1.13
      3.47), and positive surgical margins (HR = 2.95, 95% CI: 1.47-5.93). CONCLUSIONS:
      After adjusting for patient and disease characteristics, we have found that SCC
      leads to a more rapid disease course with survival that is equivalent to UC by 5
      years.

PMID- 26199178
TI  - Liver abscesses, elevated carbohydrate antigen 19-9 and concomitant malignancies.

PMID- 26199179
TI  - Re: Liver abscesses, elevated carbohydrate antigen 19-9 and concomitant
      malignancies.

PMID- 26199181
TI  - Reduced nasal growth after primary nasal repair combined with cleft lip surgery.
AB  - Nasal growth after cleft lip surgery with or without primary nasal repair was
      evaluated using lateral cephalograms. In 14 patients who underwent simultaneous
      nasal repair with primary cleft lip repair and 12 patients without simultaneous
      nasal repair, lateral cephalograms were obtained at 5 and 10 years of age.
      Lateral cephalograms of normal Japanese children were used as a control. At 5
      years of age, there were significant differences in the nasal height and
      columellar angle among the three groups. Children without simultaneous nasal
      repair had shorter noses with more upward tilt of the columella compared with the
      controls, while children with simultaneous nasal repair had much shorter noses
      and more upward tilt than those without repair. At 10 years of age, the children
      without simultaneous nasal repair showed no differences from the control group,
      while those with simultaneous repair still had shorter noses and more upward tilt
      of the columella. These findings suggest that performing nasal repair at the same
      time as primary cleft lip surgery has an adverse influence on the subsequent
      growth of the nose. 

PMID- 26199180
TI  - Changes in type 1 diabetes health indicators from high school to college.
AB  - OBJECTIVE: Evaluate trajectories of type 1 diabetes health indicators from high
      school through the first year of college. PARTICIPANTS: Seventy-four students
      with type 1 diabetes who maintained pediatric endocrinology care during the first
      year of college. METHODS: Hemoglobin A1c (HbA1c), blood glucose monitoring
      frequency, body mass index (BMI), and clinic attendance data were collected via
      retrospective medical chart review in spring 2012. Group-based trajectory models
      evaluated diabetes-related health indicators over time and identified distinct
      growth trajectory groups. RESULTS: BMI increased and clinic attendance decreased
      in the first year of college. Trajectories for other health indicators were
      heterogeneous and stable over time; 69% of students were classified as having
      stable good glycemic control. Racial minority youth and youth on conventional
      insulin regimens were disproportionally represented in higher-risk groups.
      CONCLUSIONS: Diabetes health indicators are stable or decline upon college
      entrance. Results signal the need for targeted support for college students with
      type 1 diabetes.

PMID- 26199182
TI  - Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention
      of nausea and vomiting following paclitaxel and carboplatin in patients with
      gynecologic cancers: A randomized, multicenter, phase-II trial.
AB  - AIM: Chemotherapy-induced nausea and vomiting (CINV) can affect a patient's
      quality of life, leading to poor compliance with further treatments. Previous
      studies have provided minimal data about carboplatin-based regimens. Female sex
      is a known risk factor for CINV. The purpose of this study was to evaluate
      palonosetron plus single-dose dexamethasone (DEX) for preventing CINV caused by
      carboplatin plus paclitaxel combination therapy (TC regimen) in patients with
      gynecologic cancers. MATERIAL AND METHODS: Patients were recruited for this phase
      II, multicenter, randomized trial from 12 hospitals in Hokkaido, Japan. Eligible
      patients were women with uterine cervical, endometrial or ovarian cancer
      scheduled to receive conventional TC regimen or dose-dense TC regimen; 116
      patients were randomly assigned to receive palonosetron in combination with 1-day
      DEX or 3-day DEX. RESULTS: During the overall period, complete response (CR) was
      observed in 67.9% (95% confidence interval, 53.7-80.1) of patients in the 3-day
      DEX arm, and 60.7% (95% confidence interval, 46.8-73.5) of patients in the 1-day
      DEX arm; CR was significantly lower in the 1-day DEX arm if motion sickness was
      already present (P = 0.0370). In the severe hyperemesis gravidarum cohort, CR in
      the 1-day DEX arm tended to be lower than in the 3-day DEX arm. CONCLUSION:
      Combination therapy of palonosetron and 1-day DEX was effective for subjects
      undergoing a TC regimen for gynecologic cancers. However, the possibility of
      reduced efficacy of 1-day only DEX therapy in women undergoing a TC regimen could
      not be refuted and requires further investigation.

PMID- 26199183
TI  - Syntheses, structural characterisation and electronic structures of some simple
      acyclic amino carbene complexes.
AB  - Reactions of the vinylidene complexes [M([double bond, length as m-dash]C[double
      bond, length as m-dash]CH2)(PP)Cp']PF6 with NH3 readily afford the acyclic amino
      carbene complexes [M{C(Me)NH2}(PP)Cp']PF6 [M(PP)Cp' = Fe(dppe)Cp, Ru(dppe)Cp,
      Ru(PPh3)2Cp, Ru(dppe)Cp*]. Crystallographic, spectroscopic and computational data
      support a description of these complexes in terms of a M-{C(Me)[double bond,
      length as m-dash]N(+)H2} mesomeric form, and simple sigma-coordination of the
      singlet acyclic amino carbene. 

PMID- 26199184
TI  - A mesoporous nickel counter electrode for printable and reusable perovskite solar
      cells.
AB  - A mesoporous nickel layer is used as the counter electrode in printable
      perovskite solar cells. A unique reuse process is realized in such perovskite
      solar cell devices by repeated loading of the perovskite material. Under standard
      AM1.5 illumination, the fresh device shows a promising power conversion
      efficiency of 13.6%, and an efficiency of 12.1% is obtained in the reused
      devices. 

PMID- 26199186
TI  - Genomic sequencing and analysis of the first imported Middle East Respiratory
      Syndrome Coronavirus (MERS CoV) in China.

PMID- 26199185
TI  - Potential for DNA-based identification of Great Lakes fauna: match and mismatch
      between taxa inventories and DNA barcode libraries.
AB  - DNA-based identification of mixed-organism samples offers the potential to
      greatly reduce the need for resource-intensive morphological identification,
      which would be of value both to bioassessment and non-native species monitoring.
      The ability to assign species identities to DNA sequences found depends on the
      availability of comprehensive DNA reference libraries. Here, we compile
      inventories for aquatic metazoans extant in or threatening to invade the
      Laurentian Great Lakes and examine the availability of reference mitochondrial
      COI DNA sequences (barcodes) in the Barcode of Life Data System for them. We
      found barcode libraries largely complete for extant and threatening-to-invade
      vertebrates (100% of reptile, 99% of fish, and 92% of amphibian species had
      barcodes). In contrast, barcode libraries remain poorly developed for precisely
      those organisms where morphological identification is most challenging; 46% of
      extant invertebrates lacked reference barcodes with rates especially high among
      rotifers, oligochaetes, and mites. Lack of species-level identification for many
      aquatic invertebrates also is a barrier to matching DNA sequences with physical
      specimens. Attaining the potential for DNA-based identification of mixed-organism
      samples covering the breadth of aquatic fauna requires a concerted effort to
      build supporting barcode libraries and voucher collections. 

PMID- 26199187
TI  - Hospitals send patients home without confirming home situation is adequate,
      report says.

PMID- 26199188
TI  - Brain surgery in tumor related epilepsy.

PMID- 26199190
TI  - Measurement of the Charge Carrier Mobility Distribution in Bulk Heterojunction
      Solar Cells.
AB  - Charge carrier transport through organic solar cells is fundamentally dispersive
      due to the disordered structure and complex film morphology within the
      photoactive layer. A novel application of transient photocurrent and short
      circuit variable time-delayed collection field measurements is used to
      reconstruct the complete charge carrier mobility distribution for the
      photogenerated carriers in optimized organic solar cells. 

PMID- 26199191
TI  - The Large Mitochondrial Genome of Symbiodinium minutum Reveals Conserved
      Noncoding Sequences between Dinoflagellates and Apicomplexans.
AB  - Even though mitochondrial genomes, which characterize eukaryotic cells, were
      first discovered more than 50 years ago, mitochondrial genomics remains an
      important topic in molecular biology and genome sciences. The Phylum Alveolata
      comprises three major groups (ciliates, apicomplexans, and dinoflagellates), the
      mitochondrial genomes of which have diverged widely. Even though the gene content
      of dinoflagellate mitochondrial genomes is reportedly comparable to that of
      apicomplexans, the highly fragmented and rearranged genome structures of
      dinoflagellates have frustrated whole genomic analysis. Consequently, noncoding
      sequences and gene arrangements of dinoflagellate mitochondrial genomes have not
      been well characterized. Here we report that the continuous assembled genome
      (~326 kb) of the dinoflagellate, Symbiodinium minutum, is AT-rich (~64.3%) and
      that it contains three protein-coding genes. Based upon in silico analysis, the
      remaining 99% of the genome comprises transcriptomic noncoding sequences. RNA
      edited sites and unique, possible start and stop codons clarify conserved regions
      among dinoflagellates. Our massive transcriptome analysis shows that almost all
      regions of the genome are transcribed, including 27 possible fragmented ribosomal
      RNA genes and 12 uncharacterized small RNAs that are similar to mitochondrial RNA
      genes of the malarial parasite, Plasmodium falciparum. Gene map comparisons show
      that gene order is only slightly conserved between S. minutum and P. falciparum.
      However, small RNAs and intergenic sequences share sequence similarities with P.
      falciparum, suggesting that the function of noncoding sequences has been
      preserved despite development of very different genome structures. 

PMID- 26199192
TI  - Interunit handoffs from emergency department to inpatient care: A cross-sectional
      survey of physicians at a university medical center.
AB  - BACKGROUND: Emergency department (ED) to inpatient physician handoffs are subject
      to complex challenges. We assessed physicians' perceptions of the ED admission
      handoff process and identified potential barriers to safe patient care. METHODS:
      We conducted a cross-sectional survey at a 627-bed tertiary care academic medical
      center. Eligible participants included all resident, fellow, and faculty
      physicians directly involved in admission handoffs from emergency medicine (EM)
      and 5 medical admitting services. The survey addressed communication quality,
      clinical information, interpersonal perceptions, assignment of responsibilities,
      organizational factors, and patient safety. Participants reported their responses
      via a 5-point Likert scale and an open-ended description of handoff-related
      adverse events. RESULTS: Response rates were 63% for admitting (94/150) and 86%
      for EM physicians (32/37). Compared to EM respondents, admitting physicians
      reported that vital clinical information was communicated less frequently for all
      8 content areas (P < 0.001). Ninety-four percent of EM physicians felt defensive
      at least "sometimes." Twenty-nine percent of all respondents reported handoff
      related adverse events, most frequently related to ineffective communication.
      Sequential handoffs were common for both EM and admitting services, with 78% of
      physicians reporting they negatively impacted patient care. CONCLUSION:
      Physicians reported that patient safety was often at risk during the ED admission
      handoff process. Admitting and EM physicians had divergent perceptions regarding
      handoff communication, and sequential handoffs were common. Further research is
      needed to better understand this complex process and to investigate strategies
      for improvement.

PMID- 26199193
TI  - Letter to the Editor: Pelvic Tilt in Patients Undergoing Total Hip Arthroplasty:
      When Does it Matter?

PMID- 26199194
TI  - Prevalence of canine infectious respiratory pathogens in asymptomatic dogs
      presented at US animal shelters.
AB  - OBJECTIVES: To determine the prevalence of nine canine infectious respiratory
      disease (CIRD) pathogens in asymptomatic dogs presented at animal shelters across
      the United States. METHODS: Ocular and oronasal swabs from asymptomatic dogs (n =
      503) were tested using qPCR assay for Bordetella bronchiseptica, canine
      adenovirus type 2 (CAV-2), canine distemper virus (CDV), canine herpesvirus type
      1 (CHV), canine influenza virus (CIV), canine parainfluenza virus (CPIV), canine
      respiratory coronavirus (CRCoV), Mycoplasma cynos and Streptococcus equi subsp
      zooepidemicus. RESULTS: A total of 240 (47.7%) asymptomatic dogs were PCR
      positive for at least one CIRD pathogen. Prevalence of two-, three-, four-, and
      five-pathogen cases was 12.7, 3.8, 1.8, and 0.4%, respectively. Mycoplasma cynos
      (29.2%), B. bronchiseptica (19.5%), CAV-2 (12.5%), CDV (7.4%) and CPIV (3.2%)
      were the most commonly detected pathogens. CLINICAL SIGNIFICANCE: The prevalence
      of traditional and newly emerging pathogens associated with CIRD is poorly
      defined in clinically healthy dogs. This study determined that a high percentage
      of asymptomatic shelter dogs harbor CIRD pathogens, including the newly emerging
      pathogen M. cynos and the historically prevalent pathogen B. bronchiseptica.

PMID- 26199195
TI  - Keep calm and carry on: miR-1298 prevents up-regulation of Cx43 and secures a
      quiescent vascular smooth muscle cell.

PMID- 26199196
TI  - High-rate performance of a mixed olivine cathode with off-stoichiometric
      composition.
AB  - We highlight that the off-stoichiometric compositional variation is a simply
      effective method to improve the power density of LiFe0.6Mn0.4PO4. This strategy
      does not require a supplementary separate coating and is likely applicable to
      other compositions given the feasibility of the method. 

PMID- 26199197
TI  - Surgical margin reporting in breast conserving surgery: Does compliance with
      guidelines affect re-excision and mastectomy rates?
AB  - PURPOSE: Margin status is important in guiding decisions to re-excise following
      breast-conserving surgery (BCS) for breast cancer. The College of American
      Pathologists (CAP) developed guidelines to standardize pathology reporting;
      however, compliance with margin documentation guidelines has been shown to vary.
      The aim of this retrospective study was to determine whether compliance with CAP
      guidelines affects re-excision and mastectomy rates. METHODS: We identified 1423
      patients diagnosed with breast cancer between 1998 and 2006 who underwent BCS
      with negative margins. CAP compliance was categorized as maximal, minimal, or non
      compliant. Statistical analyses were performed comparing the frequency of re
      excision and mastectomy after initial BCS according to CAP margin reporting
      guideline compliance. Data were adjusted for provider facility by including a
      clustering variable within the regression model. RESULTS: Patients with non
      compliant margin reporting were 1.7 times more likely to undergo re-excision
      and/or mastectomy than those with maximally compliant reporting. Level of
      compliance was most strongly associated with the frequency of mastectomy; non
      compliant margin reporting was associated with a 2.5-fold increase in mastectomy
      rates compared to maximally compliant reporting. The results did not
      substantially change when the analyses accounted for clustering at the provider
      facility level. CONCLUSIONS: Our findings suggest that compliance with CAP
      guidelines in pathology reporting may be associated with variation in re-excision
      and mastectomy rates following BCS.

PMID- 26199198
TI  - Bladder wall thickness in women with symptoms of overactive bladder and detrusor
      overactivity: Results from the randomised, placebo-controlled shrink study.
AB  - AIMS: Measurement of bladder wall thickness (BWT) by transvaginal ultrasound
      (TVUS) may be a less invasive method to diagnose overactive bladder (OAB) or
      detrusor overactivity (DO) and monitor response to therapy. This study assessed
      whether treatment with solifenacin affects BWT. METHODS: This was a double-blind,
      randomised, placebo-controlled, phase 4 study. Adult women with OAB symptoms
      received solifenacin 5 or 10 mg or placebo once daily for 12 weeks. The co
      primary endpoints were change from baseline to Week 12 in TVUS-measured BWT and
      urinary nerve growth factor. Only results for BWT are presented here. RESULTS:
      Overall, 547 patients were randomised, 501 patients had a baseline BWT
      measurement, and change from baseline could be calculated for 478 patients. Mean
      BWT at baseline was 5.08 mm (range 2.2-11.1, SD = 1.14) and was normally
      distributed. A significant reduction in BWT from baseline to 12 weeks versus
      placebo was observed with solifenacin 5 mg (-0.42 vs. -0.16 mm, P = 0.03), but
      not with the 10 mg dose or with pooled solifenacin, considered the primary
      comparison. Both solifenacin doses were associated with improvements in efficacy
      and patient satisfaction endpoints versus placebo. Solifenacin was well
      tolerated, with dry mouth being the most common adverse event. CONCLUSIONS: There
      was no consistent effect of solifenacin on BWT in women with OAB/DO, despite
      improvements in efficacy endpoints. This study suggests that routine clinical
      assessment of BWT with TVUS for monitoring the effects of OAB/DO treatment is not
      clinically useful. Neurourol. Urodynam. 35:819-825, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26199199
TI  - Palladium-Catalyzed Direct Dialkenylation of Cage B-H Bonds in o-Carboranes
      through Cross-Coupling Reactions.
AB  - Palladium-catalyzed direct dialkenylation of cage B(4,5)-H bonds in o-carboranes
      has been achieved with the help of a carboxylic acid directing group, leading to
      the preparation of a series of 4,5-[trans-(ArCH=CH)]2-ocarboranes in high yields
      with excellent regioselectivity. The traceless directing group, eliminated during
      the course of the reaction, is responsible for controlling regioselectivity and
      dialkenylation. A possible catalytic cycle is proposed, involving a tandem
      sequence of Pd(II) -initiated cage B-H activation, alkene insertion, beta-H
      elimination, reductive elimination, and decarboxylation.

PMID- 26199200
TI  - Free energy dependence of pure phase iron doped bismuth titanate from first
      principles calculations.
AB  - A density functional theory study of Fe substitutions in Bi2Ti2O7 photocatalyst
      (Fe-BTO) is presented. It models an experiment where H2 production of Fe-BTO
      peaked for samples loaded with 1% Fe concentration then decreased for samples
      with heavier loadings. The total energy calculations were used to determine
      defect formation energies and the chemical potential landscape that suggests the
      observed formation of Fe2O3 (in samples at 2% Fe concentration) was detrimental
      to H2 production. Doping configurations as a function of oxygen chemical
      potential are discussed, and the chemical potential ranges that avoid formation
      of the Fe2O3 phase in Fe-BTO are predicted. 

PMID- 26199201
TI  - Exonuclease containment by SUMO plus ubiquitin.

PMID- 26199202
TI  - Editorial overview: Linking protein sequence and structural changes to function
      in the era of next-generation sequencing.

PMID- 26199203
TI  - Distinctions Between Diagnostic and Classification Criteria: Comment on the
      Article by Aggarwal et al.

PMID- 26199204
TI  - Pediatric facial fractures: Demographic determinants influencing clinical
      outcomes.
AB  - OBJECTIVES/HYPOTHESIS: There is limited data linking demographic determinants to
      clinical outcomes in facial trauma, particularly when comparing regional to
      national datasets; these are the aims of the present study. STUDY DESIGN:
      Retrospective chart review. METHODS: A 10-year, retrospective single
      institutional chart review was undertaken at Children's Hospital Colorado (CHC)
      to characterize a pediatric population with facial fractures. A comparative
      analysis between the CHC and National Trauma Data Bank (NTDB) datasets was also
      conducted. RESULTS: In the CHC dataset, increased hospital stay was positively
      predicted by bilateral mandible fracture, skull, intracranial, spine, thoracic,
      abdominal, and limb injuries. Predictors of increased intensive-care unit (ICU)
      stay included skull, spine, and limb injuries. The CHC cohort had younger
      subjects, more females, fewer African Americans, and more Hispanics than the NTDB
      dataset. They were more likely to be injured by nonviolent activities than by
      altercations. Divergent facial and associated injuries between the datasets were
      found. Multivariate models showed longer length of hospital stay for the CHC
      group (P = .0085), but the NTDB group had higher ICU admission (P = .04) and
      longer lengths of ICU stay (P = .007). CONCLUSION: The demographic disparities
      (age, ethnicity, mechanism of injury, and injury type) resulted in divergent
      injury patterns and likely influenced clinical outcomes. LEVEL OF EVIDENCE: 4.

PMID- 26199205
TI  - A novel noninvasive diagnostic method for nonalcoholic steatohepatitis using two
      glycobiomarkers.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem; thus,
      discriminating nonalcoholic steatohepatitis (NASH) from NAFLD is of great
      clinical significance. For the diagnosis of NASH, liver biopsy-proven
      histological examination is the current gold standard, and noninvasive and
      reliable biomarkers are greatly needed. Recently, we found that two
      glycobiomarkers, fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein
      (Mac2bp), are useful independently for NASH diagnosis. In this study, we
      confirmed that serum Fuc-Hpt is suitable for the prediction of ballooning
      hepatocytes and that serum Mac2bp is suitable for the prediction of liver
      fibrosis severity in 124 biopsy-proven NAFLD patients (training cohort). In
      addition, we found that the combination of serum Fuc-Hpt and Mac2bp levels was an
      excellent tool for NASH diagnosis. Using receiver operating characteristic
      analyses, the area under the receiver operating characteristic curve,
      sensitivity, and specificity of the combination of these two glycobiomarkers were
      0.854, 81.1%, and 79.3%, respectively. We established a prediction model for NASH
      diagnosis using logistic regression analysis: logit (p)=-2.700+0.00242*Fuc
      Hpt+1.225*Mac2bp. To validate the prediction model, another 382 biopsy-proven
      NAFLD patients were enrolled (validation cohort). In the validation cohort, the
      area under the receiver operating characteristic curve of this model for NASH
      diagnosis was 0.844, with 71.4% and 82.3% sensitivity and specificity,
      respectively. In addition, we investigated the significance of our developed NASH
      diagnosis model in ultrasound-diagnosed NAFLD subjects who received medical
      health checkups (n = 803). Our model also could predict NAFLD disease severity in
      this larger population. CONCLUSION: The combination of serum Fuc-Hpt and Mac2bp
      can distinguish NASH from NAFLD patients. Our noninvasive model using two serum
      glycobiomarkers contributes to a novel NASH diagnostic methodology that could
      replace liver biopsy.

PMID- 26199206
TI  - Relationships between perceived aspects of home and symptoms in a cohort aged 67
      70.
AB  - The importance of the home environment increases with age. Perceived aspects of
      home influence life satisfaction, perceived health, independence in daily
      activities and well-being among very old people. However, research on health and
      perceived aspects of home among senior citizens in earlier phases of the aging
      process is lacking. Therefore, the main aim was to explore whether perceived
      aspects of home are related to number of and specific domains of symptoms in a
      cohort of people aged 67-70. Interview and observation data on aspects of home
      and health, collected with 371 individuals living in ordinary housing in urban as
      well as rural areas in southern Sweden, were used. Descriptive statistics,
      correlations, multiple linear and logistic regression models were employed. The
      results showed that the median number of symptoms was 6.0. Reporting fewer
      reported symptoms was associated with a higher meaning of home (p=0.003) and
      lower external housing related control beliefs (p=0.001) but not with usability
      in the home. High external control beliefs were significantly associated with
      symptoms from head (p=0.014), gastrointestinal (p=0.014) and tension symptoms
      (p<=0.001). Low meaning of home was significantly associated with heart-lung
      symptoms (p=0.007), and low usability was associated with depressive symptoms
      (p=0.003). In conclusion, showing that perceived aspects of home are important
      for health in terms of physical and mental symptoms, this study contributes to
      the knowledge on the complex interplay of health and home in the third age. 

PMID- 26199207
TI  - Caring for frail elders with musculoskeletal conditions and family caregivers'
      subjective well-being: The role of multidimensional caregiver burden.
AB  - OBJECTIVES: The present study examined the unique set of correlates of each
      dimension of the burden experienced by family caregivers of frail elders with
      musculoskeletal (MSK) conditions in China, and the role of caregiver burden in
      between caregiver stressors and subjective well-being. METHODS: The data was
      derived from a community sample of 494 elder-caregiver dyads from six urban
      districts of Shanghai (China). The elders were aged 75 or above, needed
      assistance in activities of daily living (ADL) and had MSK conditions. The family
      caregivers were these elders' primary caregivers and at the age of 18 or older.
      Path analysis was used to examine the proposed model. RESULTS: Care recipients'
      functional health, cognitive status and behavioral problems affected the multiple
      dimensions of caregiver burden differently. These three stressors also indirectly
      affected caregivers' subjective well-being through physical, social and
      developmental burden. CONCLUSIONS: The findings highlighted the mediator role of
      caregiver burden in between caregiver stressors and subjective well-being, which
      supported burden-as-mediator theory in understanding family caregiving for frail
      elders with musculoskeletal conditions in a Chinese context. The focus of
      intervention should be varied according to the levels of the primary stressors.
      Policy and intervention implications with regard to the ways of helping Chinese
      families care for their frail elders with MSK conditions were discussed.

PMID- 26199209
TI  - Screening, Isolation and Identification of Probiotic Producing Lactobacillus
      acidophilus Strains EMBS081 & EMBS082 by 16S rRNA Gene Sequencing.
AB  - 16S rDNA sequencing which has gained wide popularity amongst microbiologists for
      the molecular characterization and identification of newly discovered isolates
      provides accurate identification of isolates down to the level of sub-species
      (strain). Its most important advantage over the traditional biochemical
      characterization methods is that it can provide an accurate identification of
      strains with atypical phenotypic characters as well. The following work is an
      application of 16S rRNA gene sequencing approach to identify a novel species of
      Probiotic Lactobacillus acidophilus. The sample was collected from pond water
      samples of rural and urban areas of Krishna district, Vijayawada, Andhra Pradesh,
      India. Subsequently, the sample was serially diluted and the aliquots were
      incubated for a suitable time period following which the suspected colony was
      subjected to 16S rDNA sequencing. The sequence aligned against other species was
      concluded to be a novel, Probiotic L. acidophilus bacteria, further which were
      named L. acidophilus strain EMBS081 & EMBS082. After the sequence
      characterization, the isolate was deposited in GenBank Database, maintained by
      the National Centre for Biotechnology Information NCBI. The sequence can also be
      retrieve from EMBL and DDBJ repositories with accession numbers JX255677 and
      KC150145. 

PMID- 26199208
TI  - Evaluation of Internet-Based Interventions on Waist Circumference Reduction: A
      Meta-Analysis.
AB  - BACKGROUND: Internet-based interventions are more cost-effective than
      conventional interventions and can provide immediate, easy-to-access, and
      individually tailored support for behavior change. Waist circumference is a
      strong predictor of an increased risk for a host of diseases, such as
      hypertension, diabetes, and dyslipidemia, independent of body mass index. To
      date, no study has examined the effect of Internet-based lifestyle interventions
      on waist circumference change. OBJECTIVE: This study aimed to systematically
      review the effect of Internet-based interventions on waist circumference change
      among adults. METHODS: This meta-analysis reviewed randomized controlled trials
      (N=31 trials and 8442 participants) that used the Internet as a main intervention
      approach and reported changes in waist circumference. RESULTS: Internet-based
      interventions showed a significant reduction in waist circumference (mean change 
      2.99 cm, 95% CI -3.68 to -2.30, I(2)=93.3%) and significantly better effects on
      waist circumference loss (mean loss 2.38 cm, 95% CI 1.61-3.25, I(2)=97.2%) than
      minimal interventions such as information-only groups. Meta-regression results
      showed that baseline waist circumference, gender, and the presence of social
      support in the intervention were significantly associated with waist
      circumference reduction. CONCLUSIONS: Internet-based interventions have a
      significant and promising effect on waist circumference change. Incorporating
      social support into an Internet-based intervention appears to be useful in
      reducing waist circumference. Considerable heterogeneity exists among the effects
      of Internet-based interventions. The design of an intervention may have a
      significant impact on the effectiveness of the intervention.

PMID- 26199210
TI  - Ecogenomics of Geminivirus from India and Neighbor Countries: An In Silico
      Analysis of Recombination Phenomenon.
AB  - Recombination is one of the keys factor in evolutionary processes, involved in
      shaping the architecture of genomes and consequent phenotype. Understanding the
      recombination phenomenon especially among viruses will help in disease
      management. The present study aimed for in-silico analysis of recombination
      phenomenon among Begomoviruses, particularly emphasizing on viruses strains
      reported from India and neighboring countries. A total of 956 virus sequences
      have been used in this study. The Tomato yellow leaf curl China viruses, namely
      [Formula: see text] and [Formula: see text] were identified with the highest
      number of recombination event (1273). However, the Mung bean yellow mosaic India
      virus [Formula: see text] was found to have 1170 recombination event. The
      phylogenic analysis among the highly recombinant sequences was carried to get an
      insight of the evolution among viral sequences in this class of plant viruses.
      The phylogenetic analysis revealed a pattern in diversity among these virus
      strains and a split tree analysis showed diversity in the range of 0.049128335
      10.269852. This in silico analysis may pave way for a greater understanding of
      recombination phenomenon in geminiviruses and it might be helpful for strategic
      plant viral disease management. 

PMID- 26199211
TI  - Deblurring Computed Tomography Medical Images Using a Novel Amended Landweber
      Algorithm.
AB  - In computed tomography (CT), blurring occurs due to different hardware or
      software errors and hides certain medical details that are present in an image.
      Image blur is difficult to avoid in many circumstances and can frequently ruin an
      image. For this, many methods have been developed to reduce the blurring artifact
      from CT images. The problems with these methods are the high implementation time,
      noise amplification and boundary artifacts. Hence, this article presents an
      amended version of the iterative Landweber algorithm to attain artifact-free
      boundaries and less noise amplification in a faster application time. In this
      study, both synthetic and real blurred CT images are used to validate the
      proposed method properly. Similarly, the quality of the processed synthetic
      images is measured using the feature similarity index, structural similarity and
      visual information fidelity in pixel domain metrics. Finally, the results
      obtained from intensive experiments and performance evaluations show the
      efficiency of the proposed algorithm, which has potential as a new approach in
      medical image processing. 

PMID- 26199212
TI  - Examining the Variations in the Results of the Hotelling T (2) Test in Case of
      Changing Baseline Landmarks in the Bookstein Coordinates.
AB  - In many biological and biomedical investigations, the most effective way to
      analyze the forms of whole biological organs or organisms is by recording
      geometric locations of landmark points. If we want to compare shapes, then
      individuals should be translated, rotated and scaled in such a way that all of
      the individuals lie in a standard position and are centered. Bookstein conducted
      this process by choosing two landmarks as reference landmarks. Each individual is
      translated, rotated and scaled according to these reference landmarks. The aim of
      the present study was to examine the change in the p values in the case of
      choosing different baseline landmarks when performing the Hotelling T (2) test,
      which is commonly used when comparing two sample shape configurations based on
      Bookstein coordinates. For this purpose, the changes in the p values were
      investigated in shape configurations that are composed of a different number of
      landmarks by taking all of the possible paired landmark combinations at different
      variance levels and sample sizes. As a result of the present study, it was
      observed that with the increase in the landmark number, the number of possible
      baseline landmark combinations also increases and, for this reason, a substantial
      number of variations occur in the p values. Therefore, it is an important to
      decide which landmarks should be taken as reference landmarks when using the
      Bookstein coordinates. 

PMID- 26199213
TI  - Protein Degradation in Wheat Sourdough Fermentation with Lactobacillus plantarum
      M616.
AB  - Hydrolysis of wheat proteins during sourdough fermentation was determined in the
      present study. Sourdoughs were characterized with respect to cell counts, pH,
      TTA, and proteolytic activity as well as the quantity of total proteins and water
      soluble proteins. Moreover, composition analysis of total proteins and water
      soluble proteins using SDS-PAGE was carried out. Sourdough fermentation using
      Lactobacillus plantarum showed a decrease in pH and increase in TTA during
      fermentation. Fermentation resulted in hydrolysis and solubilization of wheat
      proteins. It demonstrated that protein hydrolysis in sourdough was mainly caused
      by pH-dependent activation of cereal enzymes according to change in proteolytic
      activity. 

PMID- 26199214
TI  - Virtual Screening for Potential Inhibitors of High-Risk Human Papillomavirus 16
      E6 Protein.
AB  - Human papillomavirus (HPV), a life-threatening infection, is the leading cause of
      cancer mortality among women worldwide and needs for designing anticancerous
      drugs. In the present study, we explored specific novel inhibitors against E6
      oncoprotein of high-risk HPV 16, known to inactivate tumor suppressor p53
      protein. A homology model of HPV 16 E6 was built and validated using
      bioinformatics approach. A total of 5000 drug-like compounds were downloaded from
      ZINC database based on the properties similar to the known inhibitor Jaceosidin
      (5,7-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-6-methoxy-4H-chromen-4-one). Virtual
      ligand-screening approaches were applied to screen appropriate drug-like
      compounds using molecular docking program AutoDock Vina in PyRx 0.8, and five
      best novel drug-like compounds were identified as potential competitive
      inhibitors against HPV 16 E6 compared to Jaceosidin. Two among these five
      identified most potential inhibitors, N-[(5-methyl-1H-benzimidazol-2-yl)methyl]-4
      oxo-3,4-dihydrophthalazine-1-carboxamide and 6-[3-(3-fluoro-4-methyl-phenyl)
      1,2,4-oxadiazol-5-yl]-1,4-dihydroquinoxaline-2,3-dione, were found to interact
      with E6 with binding energy of [Formula: see text] and [Formula: see text]
      kcal/mol, respectively, and form H-bonds with p53 binding site of E6 protein
      residues 113-122 (CQKPLCPEEK). These two inhibitors may help restoration of p53
      functioning. The bioinformatics approach extends a promising platform for
      developing anticancerous competitive inhibitors targeting high-risk HPV 16. 

PMID- 26199215
TI  - Influence of parity-related factors adjusted for abortion on knee osteoarthritis
      in Korean women aged 50 or older: A cross-sectional study.
AB  - OBJECTIVES: Knee osteoarthritis (OA) is pervasive in aged populations, and
      induces considerable socioeconomic expense. The objective of this study was to
      investigate the association between OA prevalence and pregnancy and parity in
      Koreans, considering for the potential effect of abortion. STUDY DESIGN: A total
      5449 women aged >=50 years with radiological knee examination results of 24,173
      participants of the 5th Korean National Health and Nutrition Examination Survey
      (2010-2012) were analyzed in a cross-sectional study. MAIN OUTCOME MEASURES:
      Association between OA prevalence (Kellgren/Lawrence grade) and pregnancy and
      parity as odds ratios (ORs) by logistic regression. RESULTS: Knee OA results were
      normal in 1996 participants (36.1%), suspected in 1012 (18.6%), mild in 781
      (14.3%), moderate in 1073 (19.7%), and severe in 617 (11.3%). Increase in number
      of pregnancies adjusted for abortion was significantly associated with increased
      OA prevalence (OR 1.081; 95% CI 1.015, 1.152). OA prevalence increased with
      parity (continuous variable) in ever-abortion (OR 1.092; 95% CI 1.009, 1.181) and
      with parity (categorical variable) with reference value set at 1-2 (P for trend;
      p=0.0195). In analyses adjusted for abortion, ever-abortion negatively influenced
      OA prevalence. Parity was not associated with OA in number of pregnancies
      unadjusted for abortion or in never-abortion women. CONCLUSIONS: This study shows
      that maternity-related factors such as pregnancy and parity were related with
      knee OA prevalence in this population-based sample of older women, and that
      relationships with abortion were stronger.

PMID- 26199217
TI  - No Sexual Dimorphism Detected in Digit Ratios of the Fire Salamander (Salamandra
      salamandra).
AB  - It has been proposed that digit ratio may be used as a biomarker of early
      developmental effects. Specifically, the second-to-fourth digit ratio (2D:4D) has
      been linked to the effects of sex hormones and their receptor genes, but other
      digit ratios have also been investigated. Across taxa, patterns of sexual
      dimorphism in digit ratios are ambiguous and a scarcity of studies in basal
      tetrapods makes it difficult to understand how ratios have evolved. Here, we
      focus on examining sex differences in digit ratios (2D:3D, 2D:4D, and 3D:4D) in a
      common amphibian, the fire salamander (Salamandra salamandra). We used graphic
      software to measure soft tissue digit length and digit bone length from X-rays.
      We found a nonsignificant tendency in males to have a lower 2D:3D than females;
      however, no sexual differences were detected in the other ratios. We discuss our
      results in the context of other studies of digit ratios, and how sex
      determination systems, as well as other factors, might impact patterns of sexual
      dimorphism, particularly in reptiles and in amphibians. Our findings suggest that
      caution is needed when using digit ratios as a potential indicator of prenatal
      hormonal effects in amphibians and highlight the need for more comparative
      studies to elucidate the evolutionary and genetic mechanisms implicated in
      sexually dimorphic patterns across taxonomic groups.

PMID- 26199218
TI  - Social Stigma and Sexual Minorities' Romantic Relationship Functioning: A Meta
      Analytic Review.
AB  - To bolster knowledge of determinants of relationship functioning among sexual
      minorities, the current meta-analysis aimed to quantitatively review evidence for
      the association between social stigma and relationship functioning as well as
      examine potential moderators. Thirty-five studies were identified, including 130
      effect sizes (39 independent; N = 10,745). Across studies, evidence was found for
      a small but significant inverse association between social stigma and
      relationship functioning. Furthermore, this association was moderated by stigma
      type (with more deleterious associations for internalized relative to perceived
      stigma) and dimension of relationship functioning (with more deleterious
      associations for affective relative to cognitive and negative relative to
      positive). Evidence for demographic moderators (region, sex, race, age) was
      generally mixed although important limitations related to unique characteristics
      of study samples are discussed. We conclude by highlighting the importance of
      social stigma for relationship functioning and point toward directions for future
      research and policy action. 

PMID- 26199216
TI  - Pulmonary CT and MRI phenotypes that help explain chronic pulmonary obstruction
      disease pathophysiology and outcomes.
AB  - Pulmonary x-ray computed tomographic (CT) and magnetic resonance imaging (MRI)
      research and development has been motivated, in part, by the quest to
      subphenotype common chronic lung diseases such as chronic obstructive pulmonary
      disease (COPD). For thoracic CT and MRI, the main COPD research tools, disease
      biomarkers are being validated that go beyond anatomy and structure to include
      pulmonary functional measurements such as regional ventilation, perfusion, and
      inflammation. In addition, there has also been a drive to improve spatial and
      contrast resolution while at the same time reducing or eliminating radiation
      exposure. Therefore, this review focuses on our evolving understanding of patient
      relevant and clinically important COPD endpoints and how current and emerging MRI
      and CT tools and measurements may be exploited for their identification,
      quantification, and utilization. Since reviews of the imaging physics of
      pulmonary CT and MRI and reviews of other COPD imaging methods were previously
      published and well-summarized, we focus on the current clinical challenges in
      COPD and the potential of newly emerging MR and CT imaging measurements to
      address them. Here we summarize MRI and CT imaging methods and their clinical
      translation for generating reproducible and sensitive measurements of COPD
      related to pulmonary ventilation and perfusion as well as parenchyma morphology.
      The key clinical problems in COPD provide an important framework in which
      pulmonary imaging needs to rapidly move in order to address the staggering
      burden, costs, as well as the mortality and morbidity associated with COPD.

PMID- 26199219
TI  - Assessing Helping and Hurting Behaviors Through the Tangram Help/Hurt Task.
AB  - Across six studies, we validated a new measure of helpful and hurtful behaviors,
      the Tangram Help/Hurt Task. Studies 1 to 3 provided cross-sectional correlational
      convergent and discriminant validity evidence for the Tangram Task using college
      based and adult online samples. Study 4 revealed that previously validated
      empathy primes increase helpful behaviors on the Tangram Task. Studies 5 and 6
      revealed that previously validated provocation manipulations increase hurtful
      behaviors on the Tangram Task. The effects of various experimental manipulations
      on the Tangram Task were similar to or larger than on other established indices
      of helpful and hurtful behaviors. In addition, motivation items in all studies
      indicate that tangram choices are indeed associated with the intent of helping
      and hurting. We discuss the advantages and limitations of the Tangram Help/Hurt
      Task relative to established measures of helpful and hurtful behaviors. 

PMID- 26199220
TI  - Cell perforation mediated by plasmonic bubbles generated by a single near
      infrared femtosecond laser pulse.
AB  - We report on transient membrane perforation of living cancer cells using
      plasmonic gold nanoparticles (AuNPs) enhanced single near infrared (NIR)
      femtosecond (fs) laser pulse. Under optimized laser energy fluence, single pulse
      treatment (tau = 45 fs, lambda = 800 nm) resulted in 77% cell perforation
      efficiency and 90% cell viability. Using dark field and ultrafast imaging, we
      demonstrated that the generation of submicron bubbles around the AuNPs is the
      necessary condition for the cell membrane perforation. AuNP clustering increased
      drastically the bubble generation efficiency, thus enabling an effective laser
      treatment using low energy dose in the NIR optical therapeutical window.

PMID- 26199221
TI  - M-Au/TiO2 (M = Ag, Pd, and Pt) nanophotocatalyst for overall solar water
      splitting: role of interfaces.
AB  - M-Au/TiO2 (M = Ag, Pd, Pt) composites were prepared through a facile one-pot
      photodeposition synthesis and evaluated for solar water splitting (SWS) with and
      without a sacrificial agent. The M-Au combination exhibits a dominant role in
      augmenting the H2 generation activity by forming a bi-metallic system. Degussa
      P25 was used as a TiO2 substrate to photodeposit Au followed by Au + M (M =
      Ag/Pd/Pt). The SWS activity of the M-Au/TiO2 was determined through
      photocatalytic H2 production in the presence of methanol as a sacrificial agent
      under one sun conditions with an AM1.5 filter. The highest H2 yield was observed
      for Pt0.5-Au1/TiO2 and was around 1.3 +/- 0.07 mmol h(-1) g(-1), with an apparent
      quantum yield (AQY) of 6.4%. Pt0.5-Au1/TiO2 also demonstrated the same activity
      for 25 cycles of five hours each for 125 h. Critically, the same Pt0.5-Au1/TiO2
      catalyst was active in overall SWS (OSWS) without any sacrificial agent, with an
      AQY = 0.8%. The amount of Au and/or Pt was varied to obtain the optimum
      composition and it was found that the Pt0.5-Au1/TiO2 composition exhibits the
      best activity. Detailed characterization by physico-chemical, spectral and
      microscopy measurements was carried out to obtain an in-depth understanding of
      the origin of the photocatalytic activity of Pt0.5-Au1/TiO2. These in-depth
      studies show that gold interacts predominantly with oxygen vacancies present on
      titania surfaces, and Pt preferentially interacts with gold for an effective
      electron-hole pair separation at Pt-Au interfaces and electron storage in metal
      particles. The Pt in Pt0.5-Au1/TiO2 is electronically and catalytically different
      from the Pt in Pt/TiO2 and it is predicted that the former suppresses the oxygen
      reduction reaction. 

PMID- 26199222
TI  - Effect of high hydrostatic pressure on the microbiological, biochemical
      characteristics of white shrimp Litopenaeus vannamei.
AB  - Using thermal processing (TP) treatment (100 C, 1-8 min) as a control, the
      effects of high hydrostatic pressure (HHP, 200-500 MPa, 2.5-20 min) on the
      microbiological and biochemical characteristics of white shrimp Litopenaeus
      vannamei were investigated. The results showed that the efficiency of polyphenol
      oxidase (PPO) inactivation and log reduction of total plate count (TPC) by HHP
      treatment were all significantly lower than by TP treatment (p < 0.05). The rate
      of inactivation for TPC and PPO all increased with the increase of HHP pressure
      and holding time (p < 0.05). The inactivation of PPO was in accordance with a
      first-order kinetics with the HHP treating time. Hardness of HHP-treated samples
      at the pressure of 300-500 MPa was higher than TP-treated samples, while the
      yield loss of HHP treatment was significantly lower than with TP treatment (p <
      0.05), long time and high pressure of HHP treatment turned the appearance of
      shrimps slightly pink. 

PMID- 26199223
TI  - Gel properties of sutchi catfish (Pangasius hypophthalmus) surimi as affected by
      selected washing process and number of washing cycles.
AB  - The gel properties of sutchi catfish surimi prepared by conventional washing and
      alkaline-saline washing method were studied for four washing cycles. Decrease (p
      < 0.05) in myoglobin content was found in alkaline washing process compared to
      conventional washing at each washing cycle. The highest hardness, breaking force
      and deformation was observed in gels prepared from alkaline-saline washing
      method. Whiteness in conventional washed surimi gels increased non-significantly
      (p < 0.05) compared to alkaline-saline-washed surimi gels. Protein bands on
      Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that the
      protein extractability was more in alkaline-saline washing and disappearance of
      bands in conventional washing method was observed between 116 and 45 kDa
      indicating less yield of protein.

PMID- 26199224
TI  - Bacterial community structure and predicted alginate metabolic pathway in an
      alginate-degrading bacterial consortium.
AB  - Methane fermentation is one of the effective approaches for utilization of brown
      algae; however, this process is limited by the microbial capability to degrade
      alginate, a main polysaccharide found in these algae. Despite its potential,
      little is known about anaerobic microbial degradation of alginate. Here we
      constructed a bacterial consortium able to anaerobically degrade alginate.
      Taxonomic classification of 16S rRNA gene, based on high-throughput sequencing
      data, revealed that this consortium included two dominant strains, designated HUA
      1 and HUA-2; these strains were related to Clostridiaceae bacterium SK082 (99%)
      and Dysgonomonas capnocytophagoides (95%), respectively. Alginate lyase activity
      and metagenomic analyses, based on high-throughput sequencing data, revealed that
      this bacterial consortium possessed putative genes related to a predicted
      alginate metabolic pathway. However, HUA-1 and 2 did not grow on agar medium with
      alginate by using roll-tube method, suggesting the existence of bacterial
      interactions like symbiosis for anaerobic alginate degradation. 

PMID- 26199225
TI  - Comprehensive two-dimensional gas chromatography coupled with time-of-flight mass
      spectrometry reveals the correlation between chemical compounds in Japanese sake
      and its organoleptic properties.
AB  - Japanese sake is a traditional alcoholic beverage composed of a wide variety of
      metabolites, which give it many types of tastes and flavors. Previously, we have
      reported that medium-chain fatty acids contribute to a fatty odor in sake
      (Takahashi, K., et al., J. Agric. Food Chem., 62, 8478-8485, 2014). In this
      study, we have reanalyzed the data obtained using two-dimensional gas
      chromatography coupled with time-of-flight mass spectrometry. The relationship
      between the chemical components in sake and specific organoleptic properties such
      as off-flavor and quality has been explored. This led to the identification of
      the type of chemical compounds present and an assessment of the numerous
      candidate compounds that correlate with such organoleptic properties in sake.
      This research provides important fundamental knowledge for the sake-brewing
      industry. 

PMID- 26199226
TI  - Vascular-like network prepared using hollow hydrogel microfibers.
AB  - One major challenge in the field of tissue engineering was the creation of
      volumetric tissues and organs in vitro. To achieve this goal, the development of
      a three-dimensional vascular-like network that extended throughout the tissue
      engineered construct was essential to supply sufficient oxygen and nutrients to
      all of the cells in the constructs. For sufficient oxygenation and nutrition of
      the tissue-engineered constructs, the distance between each microvessel-like
      channel in the network should ideally be within 100-200 MUm. In addition, the
      medium or blood should be perfused through the microchannels as soon as possible
      after the seeding of cells into the templates (scaffolds) of the constructs. In
      the present study, we proposed a novel technique for fabricating an engineered
      vascular-like network that satisfied these two requirements. The network
      comprised assembled hollow alginate hydrogel microfibers with mammalian cells
      enclosed in the gel portions. We controlled the distance between each flow
      microchannel (hollow core portions and interspace of the microfibers) to be
      within 150 MUm by using microfibers with a gel thickness of approximately 50 MUm.
      Furthermore, we confirmed that medium could be perfused into the flow channels
      quickly (within 10 min) after immobilization of the cells in the assembly. A
      human hepatoblastoma cell line (HepG2) proliferated in the gel portions of the
      microfibers and maintained their specific function during perfusion culture for 7
      days. These results showed that the novel vascular-like networks fabricated here
      had the potential to allow the creation of volumetric tissues in vitro. 

PMID- 26199227
TI  - Nonalcoholic Fatty Liver Disease Is Associated With QT Prolongation in the
      General Population.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is independently associated
      with QT prolongation among patients with diabetes. It has not yet been determined
      whether this association remains valid in the general population. We designed an
      observational study to explore this association. METHODS AND RESULTS: We
      conducted a cross-sectional analysis of 31 116 consecutive participants in our
      health management program. Heart rate-corrected QT (QTc) interval was derived
      from 12-lead electrocardiography and by Bazett's formula. NAFLD was diagnosed by
      abdominal ultrasonography and classified as none, mild, moderate, or severe,
      according to the ultrasonographic criteria. A multivariable linear regression
      model was fitted for the association between QTc interval and potential
      predictors (including demographic, anthropometric, biochemical factors, and
      comorbidities). Multivariable logistic regression analyses were fitted to assess
      the association between the severity of NAFLD and QTc prolongation, with the
      adjustment of significant predictors derived from multivariable linear
      regression. The mean QTc interval was 421.3 ms (SD 45.4 ms). In the multivariable
      linear regression analyses, mild, moderate, and severe NAFLD were associated with
      increases of 2.55, 6.59, and 12.13 ms, respectively, in QTc interval compared
      with no NAFLD (all P<0.001). In the multivariable logistic regression analyses,
      mild, moderate, and severe NAFLD were associated with an increased risk for QTc
      prolongation, with odds ratios of 1.11 (95% CI: 1.01 to 1.21, P<0.05), 1.61 (95%
      CI: 1.36 to 1.9, P<0.001), and 1.31 (95% CI: 1.16 to 2.24, P<0.01), respectively,
      in women, and 1.11 (95% CI: 1.01 to 1.21, P<0.05), 1.39 (95% CI: 1.22 to 1.59,
      P<0.001), and 1.87 (95% CI: 1.16 to 2.24, P<0.001), respectively, in men, after
      adjusting for predictors known to be associated with the QTc interval. The
      association remained significant among subgroups with or without diabetes.
      CONCLUSIONS: The severity of NAFLD was associated with a higher risk for QTc
      prolongation in the general population with and without diabetes.

PMID- 26199229
TI  - Thioredoxin Reductase 2 (Txnrd2) Regulates Mitochondrial Integrity in the
      Progression of Age-Related Heart Failure.

PMID- 26199228
TI  - Heart-Specific Knockout of the Mitochondrial Thioredoxin Reductase (Txnrd2)
      Induces Metabolic and Contractile Dysfunction in the Aging Myocardium.
AB  - BACKGROUND: Ubiquitous deletion of thioredoxin reductase 2 (Txnrd2) in mice is
      embryonically lethal and associated with abnormal heart development, while
      constitutive, heart-specific Txnrd2 inactivation leads to dilated cardiomyopathy
      and perinatal death. The significance of Txnrd2 in aging cardiomyocytes, however,
      has not yet been examined. METHODS AND RESULTS: The tamoxifen-inducible heart
      specific alphaMHC-MerCreMer transgene was used to inactivate loxP-flanked Txnrd2
      alleles in adult mice. Hearts and isolated mitochondria from aged knockout mice
      were morphologically and functionally analyzed. Echocardiography revealed a
      significant increase in left ventricular end-systolic diameters in knockouts.
      Fractional shortening and ejection fraction were decreased compared with
      controls. Ultrastructural analysis of cardiomyocytes of aged mice showed
      mitochondrial degeneration and accumulation of autophagic bodies. A dysregulated
      autophagic activity was supported by higher levels of lysosome-associated
      membrane protein 1 (LAMP1), microtubule-associated protein 1A/1B-light chain 3-I
      (LC3-I), and p62 in knockout hearts. Isolated Txnrd2-deficient mitochondria used
      less oxygen and tended to produce more reactive oxygen species. Chronic hypoxia
      inducible factor 1, alpha subunit stabilization and altered transcriptional and
      metabolic signatures indicated that energy metabolism is deregulated.
      CONCLUSIONS: These results imply a novel role of Txnrd2 in sustaining heart
      function during aging and suggest that Txnrd2 may be a modifier of heart failure.

PMID- 26199231
TI  - India sees 31% fall in open defecation over past 25 years, finds WHO.

PMID- 26199230
TI  - Hemodynamic Characteristics Including Pulmonary Hypertension at Rest and During
      Exercise Before and After Heart Transplantation.
AB  - BACKGROUND: Little is known about the hemodynamic response to exercise in heart
      failure patients at various ages before and after heart transplantation (HT).
      This information is important because postoperative hemodynamics may be a
      predictor of survival. To investigate the hemodynamic response to HT and
      exercise, we grouped our patients based on preoperative age and examined their
      hemodynamics at rest and during exercise before and after HT. METHODS AND
      RESULTS: Ninety-four patients were evaluated at rest prior to HT with right heart
      catheterization at our laboratory. Of these patients, 32 were evaluated during
      slight supine exercise before and 1 year after HT. Postoperative evaluations were
      performed at rest 1 week after HT and at rest and during exercise at 4 weeks, 3
      months, 6 months, and 1 year after HT. The exercise patients were divided into 2
      groups based on preoperative age of <=50 or >50 years. There were no age
      dependent differences in the preoperative hemodynamic exercise responses.
      Hemodynamics markedly improved at rest and during exercise at 1 and 4 weeks,
      respectively, after HT; however, pulmonary and, in particular, ventricular
      filling pressures remained high during exercise at 1 year after HT, resulting in
      normalized pulmonary vascular resistance response but deranged total pulmonary
      vascular resistance response. CONCLUSIONS: Our findings suggest that, (1) in
      patients with heart failure age <=50 or >50 years may not affect the hemodynamic
      response to exercise to the same extent as in healthy persons, and (2) total
      pulmonary vascular resistance may be more adequate than pulmonary vascular
      resistance for evaluating the exercise response after HT.

PMID- 26199232
TI  - Full self-consistency versus quasiparticle self-consistency in diagrammatic
      approaches: exactly solvable two-site Hubbard model.
AB  - Self-consistent solutions of Hedin's equations (HE) for the two-site Hubbard
      model (HM) have been studied. They have been found for three-point vertices of
      increasing complexity (Gamma = 1 (GW approximation), Gamma1 from the first-order
      perturbation theory, and the exact vertex Gamma(E)). Comparison is made between
      the cases when an additional quasiparticle (QP) approximation for Green's
      functions is applied during the self-consistent iterative solving of HE and when
      QP approximation is not applied. The results obtained with the exact vertex are
      directly related to the present open question-which approximation is more
      advantageous for future implementations, GW + DMFT or QPGW + DMFT. It is shown
      that in a regime of strong correlations only the originally proposed GW + DMFT
      scheme is able to provide reliable results. Vertex corrections based on
      perturbation theory (PT) systematically improve the GW results when full self
      consistency is applied. The application of QP self-consistency combined with PT
      vertex corrections shows similar problems to the case when the exact vertex is
      applied combined with QP sc. An analysis of Ward Identity violation is performed
      for all studied in this work's approximations and its relation to the general
      accuracy of the schemes used is provided.

PMID- 26199233
TI  - Genetics of Rapid and Extreme Size Evolution in Island Mice.
AB  - Organisms on islands provide a revealing window into the process of adaptation.
      Populations that colonize islands often evolve substantial differences in body
      size from their mainland relatives. Although the ecological drivers of this
      phenomenon have received considerable attention, its genetic basis remains poorly
      understood. We use house mice (subspecies: Mus musculus domesticus) from remote
      Gough Island to provide a genetic portrait of rapid and extreme size evolution.
      In just a few hundred generations, Gough Island mice evolved the largest body
      size among wild house mice from around the world. Through comparisons with a
      smaller-bodied wild-derived strain from the same subspecies (WSB/EiJ), we
      demonstrate that Gough Island mice achieve their exceptional body weight
      primarily by growing faster during the 6 weeks after birth. We use genetic
      mapping in large F(2) intercrosses between Gough Island mice and WSB/EiJ to
      identify 19 quantitative trait loci (QTL) responsible for the evolution of 16
      week weight trajectories: 8 QTL for body weight and 11 QTL for growth rate. QTL
      exhibit modest effects that are mostly additive. We conclude that body size
      evolution on islands can be genetically complex, even when substantial size
      changes occur rapidly. In comparisons to published studies of laboratory strains
      of mice that were artificially selected for divergent body sizes, we discover
      that the overall genetic profile of size evolution in nature and in the
      laboratory is similar, but many contributing loci are distinct. Our results
      underscore the power of genetically characterizing the entire growth trajectory
      in wild populations and lay the foundation necessary for identifying the
      mutations responsible for extreme body size evolution in nature.

PMID- 26199235
TI  - [The Functional Role of Exosomes in Cancer Biology and Their Potential as
      Biomarkers and Therapeutic Targets of Cancer].
AB  - Intercellular communication plays an important role in the regulation of various
      cellular events. In particular, cancer cells and the surrounding cells
      communicate with each other, and this intercellular communication triggers cancer
      initiation and progression through the secretion of molecules, including growth
      factors and cytokines. Recent advances in cancer biology have indicated that
      small membrane vesicles, termed exosomes, also serve as regulatory agents in
      intercellular communications. Exosomes contain functional cellular components,
      including proteins and microRNAs (miRNAs), and they transfer these components to
      recipient cells. This exosome-mediated intercellular communication leads to
      increased growth, invasion, and metastasis of cancer. Thus, researchers regard
      exosomes as important cues to understanding the molecular mechanisms of cancer
      biology. Indeed, several lines of evidence have demonstrated that exosomes can
      explain multiple aspects of cancer biology. In addition, increasing evidence
      suggests that exosomes and their specific molecules are also attractive for use
      as biomarkers and therapeutic targets in cancer. Recent reports showed the
      efficacy of a novel diagnosis by detecting component molecules of cancer-derived
      exosomes, including miRNAs and membrane proteins. Furthermore, clinical trials
      that test the application of exosomes for cancer therapy have already been
      reported. From these points of view, we will summarize experimental data that
      support the role of exosomes in cancer progression and the potential of exosomes
      for use in novel diagnostic and therapeutic approaches for cancer.

PMID- 26199236
TI  - [Clinical Practice on Thyroid Cancer in Japan].
AB  - The Japanese Society of Thyroid Surgeons and the Japanese Association of
      Endocrine Surgeons have developed the Clinical Practice Guideline on Thyroid
      Tumor in 2010 to improve clinical outcomes in patients with thyroid cancer. The
      effects of the guideline, which is unique to the clinical practice of thyroid
      oncology in Japan, remain to be determined in the future. 

PMID- 26199234
TI  - The Pace of Hybrid Incompatibility Evolution in House Mice.
AB  - Hybrids between species are often sterile or inviable. This form of reproductive
      isolation is thought to evolve via the accumulation of mutations that interact to
      reduce fitness when combined in hybrids. Mathematical formulations of this
      "Dobzhansky-Muller model" predict an accelerating buildup of hybrid
      incompatibilities with divergence time (the "snowball effect"). Although the
      Dobzhansky-Muller model is widely accepted, the snowball effect has only been
      tested in two species groups. We evaluated evidence for the snowball effect in
      the evolution of hybrid male sterility among subspecies of house mice, a recently
      diverged group that shows partial reproductive isolation. We compared the history
      of subspecies divergence with patterns of quantitative trait loci (QTL) detected
      in F2 intercrosses between two pairs of subspecies (Mus musculus domesticus with
      M. m. musculus and M. m. domesticus with M. m. castaneus). We used a recently
      developed phylogenetic comparative method to statistically measure the fit of
      these data to the snowball prediction. To apply this method, QTL were partitioned
      as either shared or unshared in the two crosses. A heuristic partitioning based
      on the overlap of QTL confidence intervals produced unambiguous support for the
      snowball effect. An alternative approach combining data among crosses favored the
      snowball effect for the autosomes, but a linear accumulation of incompatibilities
      for the X chromosome. Reasoning that the X chromosome analyses are complicated by
      low mapping resolution, we conclude that hybrid male sterility loci have
      snowballed in house mice. Our study illustrates the power of comparative genetic
      mapping for understanding mechanisms of speciation. 

PMID- 26199237
TI  - [Surgical Treatment of Thyroid Cancer].
AB  - The strategy for surgical treatment of thyroid cancer differs depending on the
      histopathological type. In papillary thyroid cancer, which accounts for most
      cases of thyroid cancer, total thyroidectomy is recommended in high-risk cases
      with tumors of more than 5 cm or with N1, EX2, or M1 tumors in Japan. On the
      other hand, ipsilateral lobectomy is performed for low-risk cases with T1N0M0.
      Our department has also added a treatment policy for the prognostic factor, age.
      Prophylactic lymph node dissection is performed in the central neck region but is
      not recommended in the lateral neck region. In follicular thyroid cancer, total
      thyroidectomy is recommended for widely invasive cancer, and hemithyroidectomy or
      ipsilateral lobectomy is performed for minimally invasive cancer. When widely
      invasive cancer is diagnosed after lobectomy, completion thyroidectomy is
      recommended. Whether minimally invasive follicular cancer with vascular invasion
      requires completion thyroidectomy is controversial. I also handle medullary
      thyroid cancer, poorly differentiated thyroid cancer, undifferentiated thyroid
      cancer, and thyroid malignant lymphoma with a different policy. It is important
      to balance a surgical treatment strategy with a molecular targeted therapy and
      radioactive iodine treatment. 

PMID- 26199238
TI  - [Radiotherapy for Thyroid Cancer].
AB  - Radioactive 131I therapy for differentiated thyroid cancer has been used since
      the 1940s and is an established and effective treatment. In contrast, external
      beam radiotherapy (EBRT) was considered to be effective for achieving local
      control but not for prolonging survival. Although clinicians were hesitant to
      administer EBRT owing to the potential radiation-induced adverse effects of 2
      dimensional (2D)-radiotherapy until 2000, it is expected that adverse effects
      will be reduced and treatment efficacy improved through the introduction of more
      advanced techniques for delivering radiation (eg, 3D-radiotherapy and intensity
      modulated radiotherapy [IMRT]). The prognosis of undifferentiated thyroid cancer
      is known to be extremely bad, although in very rare cases, multimodality therapy
      (total or subtotal resection, chemotherapy, and radiotherapy) has allowed long
      term survival. Here, we report the preliminary results of using hypofractionated
      radiotherapy for undifferentiated thyroid cancer in our institution.

PMID- 26199239
TI  - [Anti-Cancer Drugs for Thyroid Cancer].
AB  - For patients with differentiated thyroid cancer that is refractory to radioiodine
      therapy, a long-term response with conventional cytostatic drugs is uncommon, and
      treatment options have historically been limited. Outcomes for these patients
      have accordingly been limited. Development of molecular-targeted drugs for
      thyroid cancer has recently progressed, and several drugs have demonstrated
      significantly improved progression-free survival over placebo in randomized phase
      III trials. Nothing will bring us greater pleasure than meeting this hitherto
      unmet need for thyroid cancer. However, the majority of recurrent thyroid cancer
      patients have slow growing and asymptomatic disease, and these molecular-targeted
      drugs are not definitely indicated for all cases. Furthermore, toxicity is
      considerable and the expected treatment duration is more than one year. Without
      appropriate management of toxicity and patient education, these drugs will worsen
      quality of life. 

PMID- 26199240
TI  - [Chemoprevention for Familial Adenomatous Polyposis].
AB  - Colorectal cancer (CRC) is the second most common cancer in Japan. Primary cancer
      prevention is especially desired for hereditary CRC patients, owing to the high
      incidence of cancer in these patients. Prophylactic total proctocolectomy is
      generally accepted for young FAP patients; however, this procedure may reduce
      their QOL. If we could obtain effective chemopreventive drugs for FAP patients,
      prophylactic surgery could be postponed until the patients are older, or be
      avoided altogether. Thus, such drugs would bring large benefits to FAP patients.
      In this review, the history of chemopreventive drug development for FAP and the
      future prospects of chemopreventive drugs are described.

PMID- 26199242
TI  - [Analysis of the Side Effects of Docetaxel with Cyclophosphamide (TC Therapy)].
AB  - The effectiveness of TC therapy, a non-anthracycline regimen, was determined
      through the US Oncology 9735 trial, which was conducted overseas. This led to
      high expectations regarding the use of TC therapy as a postoperative adjuvant
      treatment for early-stage breast cancer. We studied 38 patients with breast
      cancer who underwent TC treatment in our department between August 2008 and
      November 2009, and discussed the development of side effects in the patients.
      Continuation of TC therapy on an outpatient basis was considered possible if
      exanthema and edema were adequately managed. 

PMID- 26199241
TI  - [Analysis of Pemetrexed Monotherapy in Advanced Non-Small Cell Lung Cancer
      Patients with Impaired Renal Function].
AB  - Toxicity and efficacy of pemetrexed monotherapy in advanced non-small-cell lung
      cancer patients with impaired renal function treated between May 2009 and May
      2012 at Gifu University Hospital were retrospectively analyzed. A total of 10 and
      17 patients had a creatinine clearance rate (Ccr) of <45 mL/min and >=45 mL/min,
      respectively. The median age was higher in the Ccr<45 mL/min group (78.9 years)
      than in the >=45 mL/min group (65.2 years). The rate of neutropenia above Grade 3
      was 30% in the Ccr<45 mL/min group and 6% in the >=45 mL/min group. Therefore,
      reducing the dose of pemetrexed should be considered in patients with impaired
      renal function. Non-hematologic toxicities were not correlated with the renal
      function. There was no treatment-related death, and most of the toxicities were
      mild and tolerable. Stable disease was observed in 6 patients (60%) in the Ccr<45
      mL/min group, and in 12 patients (70%) in the Ccr>=45 mL/min group, although some
      patients in both groups showed neither complete nor partial responses. The
      disease control rate and median progression-free survival time were 60% and 2.8
      months in the Ccr<45 mL/min group, and 70% and 2.9 months in the Ccr>=45 mL/min
      group, respectively. Thus, in this analysis, treatment with pemetrexed resulted
      in clinically equivalent efficacy in advanced non-small-cell lung cancer patients
      regardless of the state of renal function.

PMID- 26199243
TI  - [Efficacy and Safety of Pertuzumab for HER2-Positive Metastatic Breast Cancer].
AB  - The CLEOPATRA trial showed a significant improvement in the progression-free
      survival (PFS) and overall survival of patients with HER2-positive first-line
      metastatic breast cancer (MBC) who were treated with pertuzumab (PER),
      trastuzumab (TRA), and docetaxel (DTX), compared to those treated with placebo,
      TRA, and DTX. PER was approved in 2013 for treating HER2-positive MBC in Japan.
      Herein, we present the retrospective review of data from 10 HER2-positive MBC
      patients who received PER in our hospital between September 2013 and August
      2014.T he median age was 52 years (range, 45-66 years), and 7 patients were
      positive for ER.Six patients had not received any previous chemotherapy for their
      metastatic disease, while the others had received comparatively heavy
      pretreatment doses of chemotherapy.Our patients received the PER, TRA, and DTX
      regimen, although 2 patients were treated without DTX. Four patients experienced
      a partial response, 6 patients experienced stable disease (SD), and 3 patients
      experienced SD for >=6 months. The response rate was 40%, and the clinical
      benefit rate was 70%.The median PFS was 7.3 months (range, 2.5-11.5 months).
      Grade 3 neutropenia and allergic reactions were observed in 1 and 2 patients,
      respectively; no Grade 4 adverse events were observed, and thus, the regimen was
      well tolerated. Further clinical research seems to be warranted for developing
      new treatment strategies involving PER for HER2-positive MBC.

PMID- 26199244
TI  - [Transplant-Related Mortality Following Allogeneic Hematopoietic Stem Cell
      Transplantation Using Fludarabine/Busulfan-Based Reduced-Intensity Conditioning -
      A Retrospective Analysis in a Single Institution].
AB  - Reduced-intensity conditioning (RIC) has been shown to facilitate
      allogeneichematopoieticstem cell transplantation (allo-HSCT) for patients with
      comorbidities and the elderly. However, there are some concerns about transplant
      related mortality (TRM). We retrospectively analyzed 37 consecutive patients who
      received allo-HSCT using RIC from January 2005 to December 2012 in our hospital.
      All patients received fludarabine(FLU), 180 mg/m2, and intravenous busulfan(BU),
      6.4 mg/ kg (or oral BU 8 mg/kg), with or without TBI (2 or 4 Gy). Cyclosporine or
      tacrolimus alone, or in combination with shortterm methotrexate therapy was used
      for GVHD prophylaxis. Donor sources included related peripheral blood donors
      (n=4), and related (n=8) and unrelated (n=25) bone marrow donors. The underlying
      diseases were various, and 27 patients were considered to be at standard risk.
      Although one patient died of early disease progression, engraftment was achieved
      for the others. With a median follow-up of 28.5 months, the estimated 1-year and
      5-year TRMs were 13% and 20%, respectively. Five patients died of transplant
      related complications, which consisted of 2 cases of acute GVHD and 1 case each
      of interstitial pneumonitis, bronchiolitis obliterans, and infectious pneumonia.
      In conclusion, FLU/BU-based RIC is tolerable, but further optimization is needed
      to prevent transplant-related complications.

PMID- 26199245
TI  - [Study on the Antiemetic Effects of Aprepitant in Patients with Lung Cancer
      Receiving Chemotherapy with Carboplatin].
AB  - Guidelines for antiemetic therapy, such as the American Society of Clinical
      Oncology (ASCO) guidelines, recommend that aprepitant, an NK1 receptor
      antagonist, should be used in addition to conventional antiemetic therapy for
      acute and delayed nausea/vomiting caused by highly emetogenic chemotherapy.
      However, only few studies have been conducted to evaluate the efficacy of
      aprepitant in patients receiving moderately emetogenic chemotherapy. Therefore,
      we examined the antiemetic effects of additional doses of aprepitant in the next
      course in patients with lung cancer who were undergoing chemotherapy with
      carboplatin and who developed chemotherapy-induced nausea and vomiting (CINV)
      despite the preventive administration of a 5-HT3 receptor antagonist and
      dexamethasone. Consequently, the incidences of vomiting and nausea significantly
      decreased from 59% to 0% and from 91% to 64%, respectively, during the entire
      study period. Furthermore, a significant improvement in dietary intake during the
      entire study period was confirmed. These results suggest that the additional
      administration of aprepitant has high antiemetic effects in patients with lung
      cancer who are undergoing chemotherapy with carbo- platin and who show
      insufficient control of nausea/vomiting.

PMID- 26199246
TI  - [Locally Advanced Gastric Cancer Treated with Curative Gastrectomy and Showing
      Pathological Complete Response after Chemotherapy with S-1].
AB  - A 77-year-old man presented with epigastralgia. Gastrointestinal endoscopic
      examination showed advanced gastric cancer, type 3, in the distal antrum. The
      patient refused surgery and preferred chemotherapy. The regimen consisted of 80
      mg/body/day of S-1, continuously administered from day 1-14, followed by
      discontinuation for 2 weeks. After 2 courses, the patient experienced fatigue and
      recurrent vomiting. Laboratory studies revealed severe anemia; the hemoglobin
      level was 5.5 g/dL. An upper gastrointestinal endoscopy revealed pyloric stenosis
      and significant tumor reduction. Therefore, distal gastrectomy was performed.
      Histological examination did not reveal any viable cancer cells in the stomach
      and lymph nodes. Thus, a Grade 3 postchemotherapeutic effect was revealed.

PMID- 26199247
TI  - [A Case Report of Successful Chemotherapy with Tegafur/Gimeracil/Oteracil and Nab
      Paclitaxel for Gastric Cancer with Chronic Renal Failure].
AB  - An 80-year-old Japanese woman with chronic renal failure was diagnosed with
      gastric cancer and 2 primary colon cancers. The colon cancers were treated with
      laparoscopic colectomy, but the gastric cancer metastasized to the liver with
      inoperable dissemination. After operative treatment of the colon cancers, 1 year
      of combination chemotherapy consisting of tegafur/gimeracil/oteracil (TS-1(r))
      and nab-PTX was administered to treat the advanced gastric cancer. Tegafur is a
      well-known prodrug of 5-FU. Serum densitometry of 5-FU was performed to determine
      the correct dose of TS-1(r). After completion of chemotherapy, no tumor was
      detected on gastroscopy or dynamic computed tomography. The patient was well with
      no recurrence 6 months after completion of chemotherapy. CDDP, CPT-11, 5-FU, PTX,
      and DTX are known chemotherapy agents for treating gastric cancer. Renal
      excretion is not involved in the metabolism of CPT-11, 5-FU, PTX, or DTX. These
      agents are metabolized in the liver. CPT-11 metabolism depends on individual
      hepatic enzymes. Therefore, we believe that nab-PTX and TS-1(r) are safe and
      effective agents for patients with chronic renal failure and advanced gastric
      cancer. Additionally, we also conclude that using serum densitometry of 5-FU to
      guide the administration of TS-1(r) can improve both safety and efficacy.

PMID- 26199248
TI  - [A Patient Who Underwent Surgery after CR to Chemotherapy for Scirrhous Gastric
      Cancer Suspected because of Lymphangitis Carcinomatosa].
AB  - A 58-year-old woman was diagnosed with scirrhous gastric cancer suspected because
      of lymphangitis carcinomatosa. She was treated with 10 courses of S-1+CDDP
      chemotherapy. After 3 years and 6 months, CR was obtained and she underwent
      curative total gastrectomy with D2 lymph node dissection plus resection of the
      spleen and transverse colon. The pathological results of the resected specimen
      were tub2>por, pT1a, N1 (No.7), M0, CY0, P0, and HER2 (3+). After surgical
      treatment, supraclavicular lymph node metastasis occurred, and the patient
      underwent trastuzumab+capecitabine therapy, which resulted in CR for 1 year and 6
      months. Thus, for unresectable scirrhous gastric cancer, multidisciplinary
      therapy such as longterm chemotherapy including trastuzumab and surgery is
      useful.

PMID- 26199249
TI  - [Clinical Response of Metastatic Colon Cancer to Chemotherapy with S-1 and
      Oxaliplatin - A Case Report].
AB  - Chemotherapy with S-1 and oxaliplatin is a new treatment for metastatic
      colorectal cancer. We present the first case of S-1, oxaliplatin, and bevacizumab
      therapy in our hospital. The patient was a 69-year-old woman with ascending colon
      cancer and multiple lung and liver metastases. She tended to suffer from
      constipation; stenoses at the cecum and colon cancer were detected by colon
      fiberscopy. Following surgical resection of the primary tumor, the patient
      received systemic chemotherapy with S-1, oxaliplatin, and bevacizumab. Following
      chemotherapy, CT showed no cancer in the lung and cancer reduction in the liver
      or dissemination. The patient had diarrhea and no appetite at first, so we
      reduced the oxaliplatin dose by 80%. After reduction of the oxaliplatin dose, we
      could treat the patient with S-1 and oxaliplatin continuously with no toxicity. S
      1 and oxaliplatin chemotherapy is cost-effective, and has less toxicity than
      other chemotherapies, if proper measures are taken. It seemed to have a non
      inferior response rate and disease control compared to other chemotherapies, such
      as FOLFOX. Thus, this chemotherapy is a valid choice for metastatic colorectal
      cancer.

PMID- 26199250
TI  - [A Case of Concurrent Cancer in a Giant Rectal Villous Adenoma That Resulted in
      Extensive Lymph Node Metastases].
AB  - The patient was a 72-year-old man. Colonoscopy revealed a circumferential villous
      tumor with granular aggregates extending from the rectosigmoid (RS) to the lower
      rectum (Rb). Although most portions were indicative of a villous adenoma, a
      reddish coarse region at the upper rectum (Ra) was diagnosed as a concurrent
      adenocarcinoma based on biopsies. Consequently, we performed laparoscopy-assisted
      intersphincteric resection (ISR) and D3 lymph node dissection. Pathological
      diagnosis revealed multiple lymph node (LN) metastases, including ones at the
      root of the inferior mesenteric artery (IMA). Adjuvant chemotherapy was
      administered with XELOX. However, computed tomography (CT) and positron emission
      tomography (PET) conducted 6 months after surgery revealed recurrent LN
      metastasis in the mesosigmoid ie, extra-regional LN metastasis. Therefore,
      chemotherapy was reinitiated with a FOLFIRI-based regimen. Metastases were
      observed in the lateral LNs and the para-aortic LNs 9 months after surgery, and
      in the left supraclavicular LNs 12 months after surgery. Herein, we report a rare
      case of cancer concurrent with a giant villous adenoma, which resulted in
      extensive LN metastases.

PMID- 26199251
TI  - [A Case of Recurrent Breast Cancer with Carcinomatous Pleurisy Successfully
      Treated with Paclitaxel and Bevacizumab after Radical Mastectomy].
AB  - A 61-year-old postmenopausal woman with breast cancer and carcinomatous pleurisy
      was successfully treated with bevacizumab and paclitaxel. In December 2008, after
      receiving preoperative chemotherapy consisting of q3w 4 cycles of EC (E: 90
      mg/m2, C: 600 mg/m2) and 12 cycles of weekly paclitaxel (80 mg/m2), the patient
      underwent modified radical mastectomy with axillary lymph node dissection for
      right breast cancer. Pathological examination showed residual tumor cells and
      lymph node metastasis (pT4bN2M0, Stage III b). In July 2012, 3 and a half years
      later, she complained of a cough and dyspnea. Chest X-ray and computed tomography
      scans showed a pleural effusion involving the entire left thoracic cavity,
      indicating carcinomatous pleurisy. Bevacizumab and paclitaxel therapy was
      initiated. Soon thereafter, the pleural fluid disappeared, tumor marker levels
      decreased, and symptoms were ameliorated. After 6 cycles of bevacizumab and
      paclitaxel therapy, the patient continuously received 3 cycles of weekly
      paclitaxel (80 mg/m2). Two years and 4 months since the diagnosis, she has
      remained free of carcinomatous pleurisy recurrence. She is currently receiving
      hormone therapy on an outpatient basis. Bevacizumab and paclitaxel therapy is
      potentially effective for the treatment of patients with carcinomatous pleurisy,
      providing a chance for long-term survival.

PMID- 26199252
TI  - [A Case of Effective Whole-Brain Irradiation and Lapatinib/Capecitabine
      Combination Therapy for HER2-Positive Breast Cancer with Multiple Brain
      Metastases].
AB  - We report the case of a 48-year-old female patient with HER2-positive and hormone
      receptor-negative breast cancer with multiple liver metastases. She underwent 6
      cycles of FEC followed by docetaxel plus trastuzumab (TZB), resulting in a
      clinical complete response. After 15 cycles of a TZB-containing regimen, she
      complained of dizziness and nausea, and imaging examinations revealed multiple
      brain metastases. Whole-brain irradiation(33.6 Gy) was performed, and the
      chemotherapy regimen was changed to lapatinib (LAP: orally at 1,250 mg/day, every
      day) and capecitabine (CAP: orally at 2,000 mg/m2, every day for 2 weeks,
      followed by a 1-week rest interval, as 1 cycle). After 6 weeks of the new
      treatment, magnetic resonance imaging revealed marked shrinkage of brain
      metastases. A clinical complete response was maintained for 19 months. While
      brain metastasis is an important problem with treatment with TZB, LAP is drawing
      attention because of its ability to pass the blood-brain barrier because of its
      small molecular weight. LAP/CAP combination therapy may be an effective treatment
      option for brain metastases of HER2-positive breast cancer in which TZB
      essentially has no effect.

PMID- 26199254
TI  - [Leukostasis during Chronic Myelogenous Leukemia Resolved Following
      Leukapheresis].
AB  - Patients with hyperleucocytic leukemia (WBC count>10*10(4) mL) are at high risk
      of early mortality owing to pulmonary or cerebral leukostasis. Several
      researchers have reported the efficacy of immediate leukapheresis. Here, we
      report of a patient with chronic myelogenous leukemia in blast crisis and with
      pulmonary failure due to leukostasis who recovered after a combination therapy of
      leukapheresis and imatinib treatment.

PMID- 26199253
TI  - [A Case of Acute Lymphoblastic Leukemia with Adult-Onset Still's Disease-Like
      Erythema].
AB  - A 62-year-old woman developed B lymphoblastic leukemia (B-ALL) in April 2010, and
      achieved complete remission after hyper-CVAD/high-dose-MA therapy combined with
      rituximab. ALL recurred in December 2011, and remission was again achieved with
      the Japan Adult Leukemia Study Group (JALSG) ALL202 protocol combined with
      rituximab. Owing to a fever and rash that persisted from July 2012, the patient
      was examined again. On examination, redness was observed in the pharynx, and
      poorly defined oval erythemas were seen on the cheeks, posterior region of the
      neck, and upper arms. Blood test results showed high levels of ferritin, tumor
      necrosis factor (TNF)-alpha, an d C-reactive protein (CRP), and mild
      hepatosplenomegaly was identified on abdominal computed tomography (CT),
      indicative of an adult-onset Still's disease-like condition. Prednisolone therapy
      was initiated in August 2012, and remission was achieved. A second recurrence of
      ALL developed in September 2012, and although remission was again achieved using
      the JALSG ALL202 protocol, a third recurrence of ALL occurred in April 2013, and
      the patient could not be saved. In this case, adult-onset Still's disease-like
      erythema developed during the remission phase of ALL.

PMID- 26199255
TI  - Rapid contrast evaluation method based on affinity beads and backscattered
      electron imaging for the screening of electron stains.
AB  - Uranyl salts are toxic and radioactive; therefore, several studies have been
      conducted to screen for substitutes of electron stains. In this regard, the
      contrast evaluation process is time consuming and the results obtained are
      inconsistent. In this study, we developed a novel contrast evaluation method
      using affinity beads and a backscattered electron image (BSEI), obtained using
      scanning electron microscopy. The contrast ratios of BSEI in each electron stain
      treatment were correlated with those of transmission electron microscopic images.
      The affinity beads bound to cell components independently. Protein and DNA
      samples were enhanced by image contrast treated with electron stains; however,
      this was not observed for sugars. Protein-conjugated beads showed an additive
      effect of image contrast when double-stained with lead. However, additive effect
      of double staining was not observed in DNA-conjugated beads. The varying chemical
      properties of oligopeptides showed differences in image contrast when treated
      with each electron stain. This BSEI-based evaluation method not only enables
      screening for alternate electron stains, but also helps analyze the underlying
      mechanisms of electron staining of cellular structures. 

PMID- 26199256
TI  - Crimean-Congo Hemorrhagic Fever.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae
      family and Nairovirus genus. The viral genome consists of 3 RNA segments of 12 kb
      (L), 6.8 kb (M), and 3 kb (S). Crimean-Congo hemorrhagic fever (CCHF) is the most
      widespread tickborne viral infection worldwide: it has been reported in many
      regions of Africa, the Middle East, and Asia. The geographical distribution of
      CCHFV corresponds most closely with the distribution of members of the tick
      genera, and Hyalomma ticks are the principal source of human infection. In
      contrast to human infection, CCHFV infection is asymptomatic in all species.
      Treatment options for CCHF are limited; immunotherapy and ribavirin are effective
      in the treatment of CCHF; the efficacy of ribavirin in the treatment of CCHF has
      not yet been proven. This article reviews the history, epidemiology, clinical
      symptoms, pathogenesis, diagnosis, and treatment of CCHFV, as well as the
      development of a vaccine against it. 

PMID- 26199257
TI  - Rh Immunoprophylaxis for Women With a Serologic Weak D Phenotype.
AB  - It is standard practice for pregnant RhD-negative women who have not already
      formed anti-D to receive antepartum Rh immunoprophylaxis and, if they deliver an
      RhD-positive neonate, to receive postpartum Rh immunoprophylaxis. An estimated
      0.6% to 1.0% of white women have red blood cells that express a serologic weak D
      phenotype. Of these women, approximately 80% will have a weak D type 1, 2, or 3
      that could be managed safely as RhD-positive. Surveys of laboratory practice
      reveal a lack of standards for interpreting the RhD type for women with a
      serologic weak D and for determining their need for Rh immunoprophylaxis. RhD
      genotyping is recommended to determine the molecular basis of serologic weak D
      phenotypes in pregnant women as a basis for determining their candidacy for Rh
      immunoprophylaxis. 

PMID- 26199258
TI  - Relationships of Human Leukocyte Antigen-A, -B, -DRB1 Alleles, and Haplotypes in
      129 Ethnic Turkish Patients With Acute Myeloblastic Leukemia.
AB  - OBJECTIVE: To evaluate the frequencies of HLA class I (A, B) and class II (DRB1)
      alleles in acute myeloblastic leukemia (AML) and to compare them with the
      frequencies of those alleles in unrelated, healthy ethnic Turkish control
      subjects. METHOD: We investigated the relationship of HLA alleles in 129 ethnic
      Turkish patients with AML and 126 unrelated, healthy, ethnic Turkish controls
      using the polymerase chain reaction with sequence-specific oligonucleotide probes
      (PCR-SSOP) method via Luminex technology. RESULTS: Allele frequencies of HLA
      A*23, HLA-A*68, HLA-B*13, HLA-B*40, and HLA-DRB1*01 were lower in patients with
      AML compared with control individuals (P =.04, P =.02, P =.005, P = 02, and P
      =.02, respectively). In contrast, the HLA-DRB1*15 allele frequency was higher
      than in the controls (P =.01). The most commonly observed haplotype was
      A*01/B*08/DRB1*03 (5.4% vs 0.8%; P =.03) in patients with AML. In contrast, the
      most commonly observed haplotype was A*02/B*35/DRB1*04 (2.3% vs 3.2%) in
      controls. We could not find any haplotypes negatively associated with AML. Also,
      the homozygosity of HLA-A*01 and HLA-A*02 alleles were higher in patients with
      AML compared with controls (P =.046; P =.001, respectively). CONCLUSIONS: The HLA
      DRB1*15 allele, the A*01/B*08/DRB1*03 haplotypes, and the homozygosity of HLA
      A*01 and HLA-A*02 may play a presumptive predisposing factor in AML. Also, the
      HLA-A*23, HLA-A*68, HLA-B*13, HLA-B*40, and HLA-DRB1*01 alleles have been found
      to be negatively associated with AML.

PMID- 26199259
TI  - Discordance Between Tuberculin Skin Test and Interferon-gamma Release Assay in
      Children Younger Than 5 Years Who Have Been Vaccinated With Bacillus Calmette
      Guerin.
AB  - BACKGROUND: Interferon-gamma release assays (IGRAs) offer the possibility of
      improved detection of latent tuberculosis infection (LTBI). OBJECTIVE: To analyze
      discordant tuberculin skin testing (TST) and IGRA results in ethnic Croatian
      children as old as 5 years for whom there is documented exposure to an adult with
      active tuberculosis (TB) and who have been vaccinated with Bacillus Calmette
      Guerin. METHODS: In specimens from our cohort individuals, we tested the
      performances of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test and TST and
      analyzed discordant results. RESULTS: At the TST cutoff value of 10 mm or
      greater, the estimated prevalence of M. tuberculosis infection was 18.1% (31/171)
      using TST and 15.2% (26/171) using QFT-GIT. The results of these 2 tests showed
      an overall concordance of 87.7%. There was no evidence that subjects' age
      correlated with discordant results. CONCLUSIONS: The reasons for discordant
      results in young children are still unclear, which highlights the importance of
      further longitudinal studies to better understand the interpretation and any
      possible clinical implications of the results of these tests.

PMID- 26199260
TI  - An Improved Method With High Specificity for KIR2DL1 Functional Allele Typing.
AB  - As new killer-cell immunoglobulin-like receptor (KIR) alleles are discovered, a
      challenge in KIR typing is maintaining sensitivity and specificity. A single
      nucleotide polymorphism assay can be used to type functional KIR2DL1 alleles. We
      improved recently on the earlier method by using a higher-specificity assay. The
      major modifications include the development of sequence-specific primers to
      selectively amplify the transmembrane domain of all known KIR2DL1 alleles via
      polymerase chain reaction with sequence-specific primers (PCR-SSP), and using the
      PCR products as the template for a revised KIR2DL1 functional allele-typing
      assay. This modified method allows high-throughput typing with high specificity. 

PMID- 26199261
TI  - Associations Between Inflammatory Markers, Hemostatic Markers, and Microvascular
      Complications in 182 Chinese Patients With Type 2 Diabetes Mellitus.
AB  - OBJECTIVE: To examine the associations between inflammatory markers, coagulation
      and fibrinolysis parameters, and microvascular complications in 182 Chinese
      patients with type 2 diabetes mellitus (T2DM) who sought treatment at a large
      hospital in Zhejiang province, China. METHODS: We investigated the relationships
      of blood inflammatory markers with hemostatic markers in 87 patients with T2DM
      who did not have complications and 95 patients with T2DM who had microvascular
      complications. RESULTS: C-reactive protein (CRP) and interleukin-6 (IL-6) were
      significantly correlated with fibrinogen, thrombin-antithrombin III complex (TAT
      III), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor (vWF), and
      coagulation factors (F) VII in patients with T2DM who had microvascular
      complications (P <.05). Based on logistic regression analysis, the highest
      tertile groups of fibrinogen, FVII, and FVIII, corresponded to a greater risk of
      high CRP, whereas risk of high IL-6 was significantly greater in the groups with
      highest-tertile values for fibrinogen, FVII, TAT III, PAI-1, and activated
      protein C (APC). CONCLUSIONS: Elevated levels of CRP and IL-6 might be associated
      with increased coagulability and a tendency towards thrombus formation in
      patients with T2DM who have microvascular complications.

PMID- 26199262
TI  - Interference of the Hope Hemoglobin With Hemoglobin A1c Results.
AB  - Hemoglobin A1c (HbA1c) is now considered to be the marker of choice in diagnosis
      and management of diabetes mellitus, based on the results of certain landmark
      clinical trials. Herein, we report the case of a 52-year-old ethnic Southeast
      Asian Indian man with impaired glucose tolerance whose glycated hemoglobin (ie,
      HbA1c) levels, as measured via Bio-Rad D10 high-performance liquid chromatography
      (HPLC) and Roche Tina-quant immunoassay were 47.8% and 44.0%, respectively. No
      variant hemoglobin (Hb) peak was observed via the D10 chromatogram. We assayed
      the patient specimen on the Sebia MINICAP capillary electrophoresis platform; the
      HbA1c level was 6.8%, with a large variant Hb peak of 42.0%. This finding
      suggested the possible presence of the heterozygous Hb Hope, which can result in
      spuriously elevated HbA1c results on HPLC and turbidimetric immunoassays.
      Although the capillary electrophoresis system was able to identify the variant,
      the A1c results should not be considered accurate due to overlapping of the
      variant and adult Hb peaks on the electrophoretogram reading. Hb Hope is usually
      clinically silent but can present such analytical challenges. Through this case
      study, we critically discuss the limitations of various HbA1c assay methods,
      highlighting the fact that laboratory professionals need to be aware of
      occurrences of Hb Hope, to help ensure patient safety. 

PMID- 26199263
TI  - Rheumatoid Factor, Anti-Cyclic Citrullinated Peptide Antibody, C-Reactive
      Protein, and Erythrocyte Sedimentation Rate for the Clinical Diagnosis of
      Rheumatoid Arthritis.
AB  - OBJECTIVE: To explore the value of rheumatoid factor (RF), anti-cyclic
      citrullinated peptide (CCP) antibody, C-reactive protein (CRP), and the
      erythrocyte sedimentation rate (ESR) in the diagnosis of rheumatoid arthritis
      (RA). METHODS: Using rate nephelometry, chemiluminescence microparticle
      immunoassay (CMIA), and Westergren sedimentation rate testing, we detected RF,
      anti-CCP antibody, CRP, and ESR in 134 patients with RA and 50 healthy control
      individuals. RESULTS: We observed significant differences in RF, anti-CCP
      antibody, CRP, and ESR concentrations between the RA and control groups (P <.01).
      The sensitivity, specificity and accuracy in the diagnosis of RA were 91.0%,
      74.4%, and 87.0%, respectively, for RF; 88.0%, 90.4%, and 88.1%, respectively,
      for anti-CCP antibody; and 90.2%, 83.3%, and 89.5%, respectively, for the
      detection of RA via the combination of RF and anti-CCP antibody. CONCLUSION: Anti
      CCP is more specific than the other parameters we reviewed for the diagnosis of
      RA. Combined detection of the 4 parameters is beneficial when confirming a
      diagnosis of RA.

PMID- 26199264
TI  - Sensitivity of the Quidel Sofia Fluorescent Immunoassay Compared With 2 Nucleic
      Acid Assays and Viral Culture to Detect Pandemic Influenza A(H1N1)pdm09.
AB  - To confirm a diagnosis of influenza at the point of care, healthcare
      professionals may rely on rapid influenza diagnostic tests (RIDTs). RIDTs have
      low to moderate sensitivity compared with viral culture or real-time reverse
      transcription polymerase chain reaction (rRT-PCR). With the resurgence of the
      influenza A (Flu A; subtype H1N1) pandemic 2009 (pdm09) strain in the years 2013
      and 2014, we evaluated the accuracy of the United State Food and Drug
      Administration (FDA)-approved Sofia Influenza A+B Fluorescent Immunoassay to
      detect epidemic Flu A(H1N1)pdm09 in specimens from the upper-respiratory tract.
      During a 3-month period, we collected 40 specimens that tested positive via PCR
      and/or culture for Flu A of the H1N1 pdm09 subtype. Of the 40 specimens, 27
      tested positive (67.5%) via Sofia assay for Flu A. Of the 13 specimens with a
      negative result via Sofia testing, 4 had coinfection, as detected by the GenMark
      Diagnostics eSensor Respiratory Viral Panel. This sensitivity of the RIDT Sofia
      assay to detect Flu A(H1N1) pdm09 was comparable to previously reported
      sensitivities ranging from 10% to 75% for older RIDTs. 

PMID- 26199265
TI  - Development and Detection of Kidd Antibodies.
AB  - Kidd antibodies have a reputation for causing hemolytic transfusion reactions and
      hemolytic disease of the fetus and newborn. We present a case of an untransfused
      male patient who developed anti-Kidd(a) (Jk(a)) antibodies after receiving an
      allogenic renal transplant. The formation of this antibody was associated with
      exposure to the Kidd antigen expressed on the tubular epithelium of the
      transplanted kidney. The 59-year-old white male patient had received a cadaveric
      renal transplant at our clinic and returned 5 years later with proteinuria and
      elevated serum creatinine levels, consistent with nephrotic syndrome. We review
      the expression of Kidd antigens and the development and detection of Kidd
      antibodies, and discuss the case reports from the literature of Kidd antibodies
      associated with kidney-graft rejection that suggest Kidd antigens play a role as
      a minor histocompatibility antigen. 

PMID- 26199266
TI  - Low-Grade Adenosquamous Carcinoma of the Breast Developing Around a Localization
      Wire Fragment.
AB  - We present the case of a 67-year-old white woman with a history of benign biopsy
      results in the previous 10 years before she developed low-grade adenosquamous
      carcinoma around a residual localization wire fragment. A possible theory of
      carcinogenesis may be related to reparative epithelium in a healing biopsy site
      that underwent squamous metaplasia; alternately, there may have been
      carcinogenesis related to long-term metal exposure at the wire placement site. In
      vitro and in vivo studies have demonstrated a link between carcinogenesis and
      long-term exposure to various metals. This case report raises important questions
      regarding carcinogenesis in the setting of long-term metal exposure and the
      reparative response of the body at the site of injury or biopsy. 

PMID- 26199267
TI  - Case Report of Autopsy and Placental Examination After Radiofrequency Ablation of
      an Acardiac Twin.
AB  - We report the autopsy and placental findings in a monochorionic twin gestation
      complicated by twin reversed arterial perfusion (TRAP) sequence. Radiofrequency
      ablation (RFA) was performed at 24 weeks gestation to abort the acardiac fetus,
      and vaginal delivery of the co-twin and acardiac fetus occurred at 33 weeks
      gestation. An autopsy of the acardiac fetus revealed multiple congenital
      anomalies including complete absence of the upper extremities and poor
      development of the skull and facial structures. In contrast to the upper body,
      the lower half of the body, although malformed, was more developed. The
      monochorionic twin placenta showed velamentous, atrophied, proximal artery-artery
      and vein-vein intertwin vascular connections which essentially bypassed the
      placental parenchyma for the acardiac fetus. Ink injection and histologic
      examination confirmed thrombosis of these critical intertwin vascular connections
      after RFA. This report highlights the fetal and placental anatomy of TRAP
      sequence and stresses the importance of placental examination after fetal
      surgical techniques. 

PMID- 26199268
TI  - Persistent Human Chorionic Gonadotropin After Methotrexate Treatment and an
      Emergency Surgical Procedure for Ectopic Pregnancy.
AB  - The case study is a 33-year-old white female with persistently elevated serum
      human chorionic gonadotropin (hCG) levels following methotrexate treatment and
      emergency surgery for ectopic pregnancy. At the time of the first methotrexate
      dose, the serum hCG concentration was 27,995 IU/L. The laboratory was consulted
      3.5 months after the surgery, because serum hCG levels had stopped declining and
      had leveled off to around 80 to 90 IU/L but with negative urine pregnancy tests.
      Laboratory studies ruled out heterophile antibody interference and hook effect by
      multiple methods including analysis by different serum hCG assays, treatment with
      heterophile antibody blocking agents, and dilution studies. Three additional
      doses of methotrexate over six months were required for serum hCG concentrations
      to decline to undetectable levels. This case illustrates challenges that may
      arise with serum hCG measurements in management of ectopic pregnancies. Close
      collaboration between the laboratory and clinical service is key for optimal
      patient care. 

PMID- 26199269
TI  - Applying the Principles of Lean Production to Gastrointestinal Biopsy Handling:
      From the Factory Floor to the Anatomic Pathology Laboratory.
AB  - OBJECTIVES: To implement Lean principles to accommodate expanding volumes of
      gastrointestinal biopsies and to improve laboratory processes overall. DESIGN:
      Our continuous improvement (kaizen) project analyzed the current state for
      gastrointestinal biopsy handling using value-stream mapping for specimens
      obtained at a 487-bed tertiary care pediatric hospital in Dallas, Texas. We
      identified non-value-added time within the workflow process, from receipt of the
      specimen in the histology laboratory to the delivery of slides and paperwork to
      the pathologist. To eliminate non-value-added steps, we implemented the changes
      depicted in a revised-state value-stream map. RESULTS: Current-state value-stream
      mapping identified a total specimen processing time of 507 minutes, of which 358
      minutes were non-value-added. This translated to a process cycle efficiency of
      29%. Implementation of a revised-state value stream resulted in a total process
      time reduction to 238 minutes, of which 89 minutes were non-value-added, and an
      improved process cycle efficiency of 63%. CONCLUSIONS: Lean production principles
      of continuous improvement and waste elimination can be successfully implemented
      within the clinical laboratory.

PMID- 26199270
TI  - gamma-Glutamyl Transferase Testing, Change of Its Designation on the Laboratory
      Request Form, and Resulting Ratio of Inappropriate to Appropriate Use.
AB  - OBJECTIVES: To determine the effect of a modified request form on the total use
      of gamma-glutamyl transferase (GGT) usage and the ratio of inappropriate testing.
      METHODS: We modified a test request form by moving GGT from the "Liver profile"
      to the "Other" section. The criteria for appropriate GGT ordering were developed
      based on literature review and then validated by expert consensus. To determine
      the appropriateness of GGT requests, we reviewed the medical records of patients
      for whom GGT testing was requested, before and after the change in the request
      form. RESULTS: The total number of GGT tests performed was reduced from 81,020
      tests before the change to 35,816 tests after the change (a 44.2% reduction). Of
      the 349 patients whose records we examined, GGT testing was ordered for 169
      patients before the change in the form and for 180 patients after the change. The
      percentage of inappropriate GGT ordering was nonsignificantly reduced (from 85.8%
      to 81.7%; P =.30). CONCLUSIONS: The change in the classification of GGT testing
      on the laboratory request form was associated with a reduction in total test
      usage and nonsignificantly associated with a reduction in the proportion of
      inappropriate testing. Hence, we strongly recommend that physicians be given
      feedback and education concerning clinical indication.

PMID- 26199272
TI  - The Impact of Simulated Nature on Patient Outcomes: A Study of Photographic Sky
      Compositions.
AB  - OBJECTIVE: To examine whether incorporation of simulated nature, in the form of
      ceiling mounted photographic sky compositions, influences patient outcomes.
      BACKGROUND: Previous studies have shown that most forms of nature exposure have a
      positive influence on patients. However, earlier studies have mostly focused on
      wall-hung nature representations. The emergence of simulated nature products has
      raised the question regarding the effects of the new product on patient outcomes.
      METHODS: A between-subject experimental design was adopted, where outcomes from
      five inpatient rooms with sky composition ceiling fixture were compared to
      corresponding outcomes in five identical rooms without the intervention. Data
      were collected from a total of 181 subjects on 11 outcomes. Independent sample
      tests were performed to identify differences in mean outcomes. RESULT:
      Significant positive outcomes were observed in environmental satisfaction and
      diastolic blood pressure (BP). Environmental satisfaction in the experimental
      group was 12.4% higher than the control group. Direction of association for
      diastolic BP, nausea/indigestion medication, acute stress, anxiety, pain, and
      environmental satisfaction were consistent with a priori hypothesis. A post hoc
      exploratory assessment involving patients who did not self-request additional
      pain and sleep medication demonstrated confirmatory directions for all outcomes
      except Systolic BP, and statistically significant outcomes for Acute Stress and
      Anxiety-Acute Stress and Anxiety levels of the experimental group subjects was
      53.4% and 34.79% lower, respectively, than that of the control group subjects.
      CONCLUSION: Salutogenic benefits of photographic sky compositions render them
      better than traditional ceiling tiles and offer an alternative to other nature
      interventions.

PMID- 26199271
TI  - Changes in J-SOAP-II and SAVRY Scores Over the Course of Residential, Cognitive
      Behavioral Treatment for Adolescent Sexual Offending.
AB  - Although the Juvenile Sex Offender Assessment Protocol-II (J-SOAP-II) and the
      Structured Assessment of Violence Risk in Youth (SAVRY) include an emphasis on
      dynamic, or modifiable factors, there has been little research on dynamic changes
      on these tools. To help address this gap, we compared admission and discharge
      scores of 163 adolescents who attended a residential, cognitive-behavioral
      treatment program for sexual offending. Based on reliable change indices, one
      half of youth showed a reliable decrease on the J-SOAP-II Dynamic Risk Total
      Score and one third of youth showed a reliable decrease on the SAVRY Dynamic Risk
      Total Score. Contrary to expectations, decreases in risk factors and increases in
      protective factors did not predict reduced sexual, violent nonsexual, or any
      reoffending. In addition, no associations were found between scores on the
      Psychopathy Checklist:Youth Version and levels of change. Overall, the J-SOAP-II
      and the SAVRY hold promise in measuring change, but further research is needed.

PMID- 26199274
TI  - Theoretical examination of behavioural feedback in the application of
      teledietetics to weight reduction.
AB  - INTRODUCTION: Behavioural feedback can be attained through electronic self
      monitoring with teledietetics. This study examined the theoretical framework of
      the theory of planned behaviour, which suggests that behavioural feedback
      contributes to the intention to initiate and maintain weight loss. METHODS: A
      quasi-experiment involving adults aged 20-50 years with a body mass index greater
      than 23 kg/m(2) was conducted. The experimental group (EG) comprised 25
      participants who used electronic dietary records for self-monitoring. The control
      group (CG) comprised 25 participants who used paper-format dietary records for
      self-monitoring. Data pertaining to the theory of planned behaviour were obtained
      using a self-administered questionnaire. After an initial measurement, each
      participant's body weight was measured again at Week 12 and at Week 24, following
      a 12-week observation period. Hierarchical regression analyses of planned
      behaviour components were conducted for each power to predict the participants'
      intentions to lose 10% of their body weight. Logistic regression analysis was
      performed to investigate the odds ratio of intention, perceived behavioural
      control (PBC) and the group effect (CG vs EG) for predicting the initiation and
      maintenance of 10% weight loss. RESULTS: At Week 12, the odds ratios for
      intention, the PBC and the group effect were 2.154, 0.330 and 0.654,
      respectively, and those at Week 24 were 3.255, 0.499 and 24.592, respectively.
      The group effect contributed significantly to weight-loss maintenance at Week 24.
      DISCUSSION: Behavioural feedback through electronic self-monitoring improved the
      intention to achieve weight-loss maintenance, which may indicate the importance
      of behaviour reflection in weight-loss maintenance.

PMID- 26199273
TI  - Birth weight and later life adherence to unhealthy lifestyles in predicting type
      2 diabetes: prospective cohort study.
AB  - OBJECTIVES: To prospectively assess the joint association of birth weight and
      established lifestyle risk factors in adulthood with incident type 2 diabetes and
      to quantitatively decompose the attributing effects to birth weight only, to
      adulthood lifestyle only, and to their interaction. DESIGN: Prospective cohort
      study. SETTING: Health Professionals Follow-up Study (1986-2010), Nurses' Health
      Study (1980-2010), and Nurses' Health Study II (1991-2011). PARTICIPANTS: 149,794
      men and women without diabetes, cardiovascular disease, or cancer at baseline.
      MAIN OUTCOME MEASURE: Incident cases of type 2 diabetes, identified through self
      report and validated by a supplementary questionnaire. Unhealthy lifestyle was
      defined on the basis of body mass index, smoking, physical activity, alcohol
      consumption, and the alternate healthy eating index. RESULTS: During 20-30 years
      of follow-up, 11,709 new cases of type 2 diabetes were documented. The
      multivariate adjusted relative risk of type 2 diabetes was 1.45 (95% confidence
      interval 1.32 to 1.59) per kg lower birth weight and 2.10 (1.71 to 2.58) per
      unhealthy lifestyle factor. The relative risk of type 2 diabetes associated with
      a combination of per kg lower birth weight and per unhealthy lifestyle factor was
      2.86 (2.26 to 3.63), which was more than the addition of the risk associated with
      each individual factor, indicating a significant interaction on an additive scale
      (P for interaction < 0.001). The attributable proportions of joint effect were
      22% (95% confidence interval 18.3% to 26.4%) to lower birth weight alone, 59%
      (57.1% to 61.5%) to unhealthy lifestyle alone, and 18% (13.9% to 21.3%) to their
      interaction. CONCLUSION: Most cases of type 2 diabetes could be prevented by the
      adoption of a healthier lifestyle, but simultaneous improvement of both prenatal
      and postnatal factors could further prevent additional cases.

PMID- 26199275
TI  - Participant experiences in a smartphone-based health coaching intervention for
      type 2 diabetes: A qualitative inquiry.
AB  - INTRODUCTION: We investigated the experience of individuals diagnosed with type 2
      diabetes mellitus (T2DM) who participated in an intervention in which the key
      elements were the provision of a smartphone and self-monitoring software. The
      interviews focused on use of a smartphone and the effects on motivation for
      health behavior change. METHODS: This was a qualitative evaluation of
      participants in a larger T2DM self-management randomized controlled trial (RCT)
      conducted at the Black Creek Community Health Centre (BCCHC) in Toronto, Canada
      (ClinicalTrials.gov Identifier: NCT02036892). The study is based on semi
      structured interviews (n = 11) that were audio taped and analyzed with a thematic
      analytic approach. The RCT compared the effectiveness of six months of smartphone
      based self-monitoring and health coaching with a control group who received
      health coaching without internet or smartphone-based assistance. RESULTS:
      Qualitative data analyses resulted in derivation of four major themes that
      describe participant experience: (a) 'smartphone and software', describes
      smartphone use in relation to health behavior change; (b) 'health coach'
      describes how client/health coach relationships were assisted by smartphone use;
      (c) 'overall experience' describes perceptions of the overall intervention; and
      (d) 'frustrations in managing chronic conditions' describes difficulties with the
      complexities of T2DM management from a patient perspective. DISCUSSION: Findings
      suggest that interventions with T2DM assisted by smartphone software and health
      coaches actively engage individuals in improved hemoglobin A1c (HbA1c) control.

PMID- 26199276
TI  - Speed and accuracy of mobile BlackBerry Messenger to transmit chest radiography
      images from a small community emergency department to a geographically remote
      referral center.
AB  - BACKGROUND: Small emergency departments (EDs) may rely on radiologists at remote
      centers for interpretations of chest radiographs (CXRs). We investigated
      systematic transmission of CXR images from a small ED to a geographically remote
      referral center using the mobile BlackBerry Messenger (BBM) application. METHODS:
      Investigators obtained de-identified CXR images of consecutive ED patients via
      mobile phone camera. Each CXR image, along with a brief clinical history, was
      sent via BBM to an emergency physician located at a remote referral site, and the
      receiving physician replied via BBM to confirm reception. All communications,
      image generation, and image analysis was conducted on mobile phones. The primary
      outcome was the proportion of BBMs received within two minutes of sending; the
      secondary outcome was the proportion of BBM replies to the sending physician
      within five minutes. Image accuracy-comparing the radiologist's interpretation
      with the receiving emergency physician's interpretation-was estimated using
      predefined criteria. RESULTS: Of 1281 consecutive ED patients, 231 (18.0 %) had
      CXRs obtained, 320 CXRs were analyzed and 611 BBMs sent. All BBMs (100.0%, 95%
      confidence interval (CI) 99.4-00.0) arrived within two minutes; 595 BBMs (97.4%,
      95% CI 95.8-98.4) were replied to within five minutes. Of the 58 CXRs with
      abnormalities requiring intervention, there were 55 concordances (overall
      agreement 94.2%, 95% CI 85.9-98.3; kappa 0.95, 95% CI 0.89-1.0) CONCLUSION:
      Systematic transmission of CXR images from a small ED to a remote large center
      using mobile phones may be a safe and effective strategy to rapidly communicate
      important patient information.

PMID- 26199277
TI  - Prenatal diagnosis and telemedicine consultation of fetal urologic disorders.
AB  - In Arkansas, telemedicine is used commonly in obstetrics through Antenatal and
      Neonatal Guidelines, Education and Learning System (ANGELS), the existing
      statewide telemedicine network. This network is used primarily for tele
      ultrasound and maternal-fetal medicine consultation. This study is a
      retrospective case series, describing all the patients who had a prenatally
      diagnosed urologic anomaly that required prenatal urologic consultation. From
      2009-2013, approximately 1300 anomalies were recorded in the Arkansas Fetal
      Diagnosis and Management (AFDM) database, 14% of which were urologic anomalies.
      Twenty-six cases required prenatal urologic consultation, 25 of which were
      conducted via telemedicine. Teleconsultation allowed patients to combine maternal
      fetal medicine and urologic consultations in one visit, saving time and effort
      and ultimately, for most patients, providing reassurance that delivery could be
      accomplished locally with postnatal follow-up already arranged. While there are
      several studies reporting the use of telemedicine for various subspecialty
      consultations, to our knowledge, this is the first to describe the use of
      telemedicine for prenatal urology consultation. Future research could randomize
      patients prospectively to allow comparison of both the outcomes as well as the
      patient experience. 

PMID- 26199278
TI  - Using TV white space spectrum to practise telemedicine: A promising technology to
      enhance broadband internet connectivity within healthcare facilities in rural
      regions of developing countries.
AB  - The following correspondence provides an overview of TV White Space (TVWS)
      technology, regulations, and potential applications to the health care sector.
      This report also introduces "Project Kgolagano," a Botswana-based initiative
      representing the first endeavour to utilize TVWS internet connection for
      practising telemedicine. TV "white space" refers to the previously unused, wasted
      spectrum within TV radiofrequency channels that can now be leveraged to obtain
      broadband internet access. TVWS represents a less costly, faster, and farther
      reaching internet connection that is a promising option for connecting the
      previously unconnected populations of remote and underserved areas. The Botswana
      University of Pennsylvania Partnership, Microsoft, Botswana Innovation Hub, Vista
      Life Sciences, and Global Broadband Solutions have partnered together to bring
      TVWS wireless broadband access to healthcare facilities in poorly connected
      regions of Botswana (Lobatse, Francistown, Maun, Gaborone) in order to improve
      healthcare delivery and facilitate telemedicine in dermatology, cervical cancer
      screening, and family medicine (HIV/AIDS, TB, general adult and pediatric
      medicine). 

PMID- 26199279
TI  - Phosphatase control of 4E-BP1 phosphorylation state is central for glycolytic
      regulation of retinal protein synthesis.
AB  - Control of protein synthesis in insulin-responsive tissues has been well
      characterized, but relatively little is known about how this process is regulated
      in nervous tissues. The retina exhibits a relatively high protein synthesis rate,
      coinciding with high basal Akt and metabolic activities, with the majority of
      retinal ATP being derived from aerobic glycolysis. We examined the dependency of
      retinal protein synthesis on the Akt-mTOR signaling and glycolysis using ex vivo
      rat retinas. Akt inhibitors significantly reduced retinal protein synthesis but
      did not affect glycolytic lactate production. Surprisingly, the glycolytic
      inhibitor 2-deoxyglucose (2-DG) markedly inhibited Akt1 and Akt3 activities, as
      well as protein synthesis. The effects of 2-DG, and 2-fluorodeoxyglucose (2-FDG)
      on retinal protein synthesis correlated with inhibition of lactate production and
      diminished ATP content, with all these effects reversed by provision of d
      mannose. 2-DG treatment was not associated with increased AMPK, eEF2, or
      eIF2alpha phosphorylation; instead, it caused rapid dephosphorylation of 4E-BP1.
      2-DG reduced total mTOR activity by 25%, but surprisingly, it did not reduce
      mTORC1 activity, as indicated by unaltered raptor-associated mTOR
      autophosphorylation and ribosomal protein S6 phosphorylation. Dephosphorylation
      of 4E-BP1 was largely prevented by inhibition of PP1/PP2A phosphatases with
      okadaic acid and calyculin A, and inhibition of PPM1 phosphatases with cadmium.
      Thus, inhibition of retinal glycolysis diminished Akt and protein synthesis
      coinciding with accelerated dephosphorylation of 4E-BP1 independently of mTORC1.
      These results demonstrate a novel mechanism regulating protein synthesis in the
      retina involving an mTORC1-independent and phosphatase-dependent regulation of 4E
      BP1. 

PMID- 26199280
TI  - When two obese parents are worse than one! Impacts on embryo and fetal
      development.
AB  - The prevalence of overweight and obesity in reproductive-age adults is increasing
      worldwide. While the effects of either paternal or maternal obesity on gamete
      health and subsequent fertility and pregnancy have been reported independently,
      the combination of having both parents overweight/obese on fecundity and
      offspring health has received minimal attention. Using a 2 * 2 study design in
      rodents we established the relative contributions of paternal and maternal
      obesity on fetal and embryo development and whether combined paternal and
      maternal obesity had an additive effect. Here, we show that parental obesity
      reduces fetal and placental weights without altering pregnancy establishment and
      is not dependent on an in utero exposure to a high-fat diet. Interestingly
      combined parental obesity seemed to accumulate both the negative influences of
      paternal and maternal obesity had alone on embryo and fetal health rather than an
      amplification, manifested as reduced embryo developmental competency, reduced
      blastocyst cell numbers, impaired mitochondrial function, and alterations to
      active and repressive embryonic chromatin marks, resulting in aberrant placental
      gene expression and reduced fetal liver mtDNA copy numbers. Further understanding
      both the maternal cytoplasmic and paternal genetic interactions during this early
      developmental time frame will be vital for understanding how developmental
      programming is regulated and for the proposition of interventions to mitigate
      their effects. 

PMID- 26199282
TI  - Recruiting 5000 more GPs will be tough, NHS chief tells MPs.

PMID- 26199281
TI  - High-dose testosterone and dehydroepiandrosterone induce cardiotoxicity in rats:
      Assessment of echocardiographic, morphologic, and oxidative stress parameters.
AB  - The aim of this study is to assess cardiotoxic effect of testosterone (TES) and
      dehydroepiandrosterone (DHEA) in Sprague Dawley rats. We compared the impact of
      subacute (14 days) and subchronic (90 days) administration of suprapharmacologic
      doses of TES and DHEA on body weight, locomotor activity, muscle strength,
      echocardiographic parameters, heart histopathology, and oxidative stress markers
      with the control group. Testosterone (10, 30, and 100 mg/100 g body weight) and
      DHEA (10 mg/100 g body weight) administration decreased the body weights and
      locomotor activity (p < 0.05), and the combination of both increased muscle
      strength (p < 0.05) in rats. In our histopathological evaluation, misshapen cell
      nuclei, disorganized myocardial fibers, and leukocytic infiltrates were observed
      in high-dose TES (100 mg/100 g)-treated rats, especially on day 14. On day 90,
      mild changes such as misshapen cell nuclei, disorganized myocardial fibers, and
      leukocytic infiltrates were observed in TES and DHEA-treated groups. According to
      our echocardiographic study on day 14 and day 90, TES, especially at high doses,
      induced increase in left ventricular posterior wall diameter and ejection
      fraction (p < 0.05). In this study, blood oxidative stress marker malondialdehyde
      was increased slightly but not significantly in TES and DHEA groups. On the other
      hand, antioxidant enzymes such as SOD and glutathione peroxidase (GSH-Px) levels
      were slightly but not significantly increased in TES and DHEA groups. These data
      demonstrate that the potential risk to cardiac health due to exogenous androgen
      use may be related to oxidative stress in rats. 

PMID- 26199283
TI  - Population-based analysis of hospitalizations in a West-European region revealed
      major changes in hospital utilization for patients with systemic lupus
      erythematosus over the period 2001-2012.
AB  - OBJECTIVE: The objective of this paper is to evaluate hospital admissions in
      systemic lupus erythematosus (SLE) patients through a retrospective population
      based study analyzing hospitalization data during 2001-2012 in Sardinia, an
      Italian region with universal health system coverage. METHODS: Data on the
      hospital discharge records with the ICD-9-CM code for SLE (710.0) were obtained
      from the Department of Health and Hygiene and analyzed, mostly focusing on
      primary and non-primary diagnosis and Diagnosis-Related Group (DRG) code. In
      order to establish the significance of the annual trend for number and type of
      primary and non-primary discharge diagnosis, the two-tailed Cochran-Armitage test
      for trend was applied. In order to estimate SLE prevalence, data from
      administrative database and medical records were assembled. RESULTS: This study
      included 6222 hospitalizations in 1675 patients (87% women). Hospitalizations
      with SLE as primary diagnosis were 3782 (58.0%) and significantly decreased
      during the study period. The annual number of renal, hematologic and
      neuropsychiatric disorders as non-primary diagnosis associated with SLE remained
      constant; however, their percentage increased (p < 0.0001) because of a declining
      number of admissions for SLE without associated diagnosis and without
      complications. Hospitalizations with SLE as non-primary diagnosis showed a
      significant upward trend in number and percentage of cerebrovascular accident (p
      = 0.0004), acute coronary syndrome (p = 0.0004) and chronic renal failure (p =
      0.0003) as underlying primary diagnosis, while complications of pregnancy, labor
      and childbirth (p = 0.3375), malignancies (p = 0.6608) and adverse drug reactions
      (p = 0.2456) did not show statistically significant changes. Infections showed an
      increasing trend between 2001 and 2012 but did not reach statistical significance
      (p = 0.0304). After correction for hospitalization (93.8%) and survival (91.1%)
      rates calculated over the study period, the 2012 SLE prevalence in Sardinia was
      estimated to be 99.3 per 100,000 inhabitants. CONCLUSIONS: While overall
      hospitalizations for SLE patients declined, those for cerebrovascular accident,
      acute coronary syndrome and chronic renal failure as underlying primary diagnosis
      increased during the study period.

PMID- 26199284
TI  - Rapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch
      Repair Mutants.
AB  - Resistance to cancer therapy is a major obstacle in the long-term treatment of
      cancer. A greater understanding of drug resistance mechanisms will ultimately
      lead to the development of effective therapeutic strategies to prevent resistance
      from occurring. Here, we exploit the mutator phenotype of mismatch repair
      defective yeast cells combined with whole genome sequencing to identify drug
      resistance mutations in key pathways involved in the development of
      chemoresistance. The utility of this approach was demonstrated via the
      identification of the known CAN1 and TOP1 resistance targets for two compounds,
      canavanine and camptothecin, respectively. We have also experimentally validated
      the plasma membrane transporter HNM1 as the primary drug resistance target of
      mechlorethamine. Furthermore, the sequencing of mitoxantrone-resistant strains
      identified inactivating mutations within IPT1, a gene encoding
      inositolphosphotransferase, an enzyme involved in sphingolipid biosynthesis. In
      the case of bactobolin, a promising anticancer drug, the endocytosis pathway was
      identified as the drug resistance target responsible for conferring resistance.
      Finally, we show that that rapamycin, an mTOR inhibitor previously shown to alter
      the fitness of the ipt1 mutant, can effectively prevent the formation of
      mitoxantrone resistance. The rapid and robust nature of these techniques, using
      Saccharomyces cerevisiae as a model organism, should accelerate the
      identification of drug resistance targets and guide the development of novel
      therapeutic combination strategies to prevent the development of chemoresistance
      in various cancers. 

PMID- 26199285
TI  - Reagent and Data Resources for Investigation of RNA Binding Protein Functions in
      Drosophila melanogaster Cultured Cells.
AB  - RNA binding proteins (RBPs) are involved in many cellular functions. To
      facilitate functional characterization of RBPs, we generated an RNA interference
      (RNAi) library for Drosophila cell-based screens comprising reagents targeting
      known or putative RBPs. To test the quality of the library and provide a baseline
      analysis of the effects of the RNAi reagents on viability, we screened the
      library using a total ATP assay and high-throughput imaging in Drosophila S2R+
      cultured cells. The results are consistent with production of a high-quality
      library that will be useful for functional genomics studies using other assays.
      Altogether, we provide resources in the form of an initial curated list of
      Drosophila RBPs; an RNAi screening library we expect to be used with additional
      assays that address more specific biological questions; and total ATP and image
      data useful for comparison of those additional assay results with fundamental
      information such as effects of a given reagent in the library on cell viability.
      Importantly, we make the baseline data, including more than 200,000 images,
      easily accessible online. 

PMID- 26199286
TI  - Large two-centre study into the prevalence of Mycoplasma genitalium and
      Trichomonas vaginalis in the Netherlands.
AB  - Mycoplasma genitalium and Trichomonas vaginalis are common sexually transmitted
      infections (STIs). In the Netherlands, testing for M. genitalium and T. vaginalis
      is not recommended for first-line STI screening. Recent reports about the
      increasing antimicrobial resistance in M. genitalium raise concern about the
      adequacy of current empirical treatment regimens. It is necessary to have insight
      in the prevalence of M. genitalium and T. vaginalis in order to evaluate current
      first-line STI screening and treatment protocols. During a five-month period,
      samples sent to two large medical microbiology diagnostic centres in the
      Netherlands for STI screening (Chlamydia trachomatis and Neisseria gonorrhoeae)
      were retrospectively tested for the prevalence of M. genitalium and T. vaginalis
      using the Diagenode S-DiaMGTV kit. A total of 1569 samples from 1188 unique
      patients (55.4% female) were tested. M. genitalium was the second most prevalent
      STI detected (4.5% of the patients), after C. trachomatis (8.3%). T. vaginalis
      was detected in 1.4% of the patients, comparable to the prevalence of N.
      gonorrhoeae (1.3%). Dual infections were only detected in a small number of
      patients (1.0%). Incorporation of M. genitalium into routine STI screening should
      be considered, because of its relatively high prevalence, the consequences of its
      detection for antibiotic treatment and because of the availability of easy-to-use
      molecular diagnostic tests. For T. vaginalis, routine screening may be
      considered, depending on local prevalence and (sub)population.

PMID- 26199287
TI  - The Contribution of Smoking to Educational Gradients in U.S. Life Expectancy.
AB  - Researchers have documented widening educational gradients in mortality in the
      United States since the 1970s. While smoking has been proposed as a key
      explanation for this trend, no prior study has quantified the contribution of
      smoking to increasing education gaps in longevity. We estimate the contribution
      of smoking to educational gradients in life expectancy using data on white men
      and women ages 50 and older from the National Longitudinal Mortality Study (N =
      283,430; 68,644 deaths) and the National Health Interview Survey (N = 584,811;
      127,226 deaths) in five periods covering the 1980s to 2006. In each period,
      smoking makes an important contribution to education gaps in longevity for white
      men and women. Smoking accounts for half the increase in the gap for white women
      but does not explain the widening gap for white men in the most recent period.
      Addressing greater initiation and continued smoking among the less educated may
      reduce mortality inequalities. 

PMID- 26199289
TI  - The Culturally Diverse Nursing Student: A Review of the Literature.
AB  - PURPOSE: The purpose of this article is to discuss the facilitators and barriers
      to the retention and graduation of the culturally diverse nursing student using
      the social ecological model (SEM). DESIGN: Literature review. METHOD: A review of
      the literature was conducted and the SEM was used to evaluate the facilitators
      and barriers to the success of culturally diverse nursing students. FINDINGS: The
      SEM is an appropriate means to evaluate the facilitators and barriers to the
      retention and success of the culturally diverse nursing student. Researchers link
      health disparities in marginalized populations with diversity of the health care
      workforce. Consequently, the SEM provides a multidimensional view of the problem
      of focus, while providing a guide for the development for sustainable solutions
      to address the issues. Additional research is necessary using a social
      determinant of health model such as the SEM to facilitate dialogue and change in
      current retention strategies.

PMID- 26199288
TI  - Associations Between Family Ratings on Experience With Care and Clinical Quality
      of-Care Measures for Nursing Home Residents.
AB  - Several states are currently collecting and publicly reporting nursing home
      resident and/or family member ratings of experience with care in an attempt to
      improve person-centered care in nursing homes. Using the 2008 Maryland nursing
      home family survey reports and other data, this study performed both facility-
      and resident-level analyses, and estimated the relationships between family
      ratings of care and several long-term care quality measures (pressure ulcers,
      overall and potentially avoidable hospitalizations, and mortality) after
      adjustment for resident characteristics. We found that better family evaluations
      of overall and specific aspects of care may be associated with reduced rates of
      risk-adjusted measures at the facility level (range of correlation coefficients: 
      .01 to -.31). Associations of overall experience ratings tended to persist after
      further adjustment for common nursing home characteristics such as nurse staffing
      levels. We conclude that family ratings of nursing home care complement other
      types of performance measures such as risk-adjusted outcomes. 

PMID- 26199290
TI  - Supply and demand: Will we have enough vascular surgeons by 2030?
AB  - The increase in prevalence of certain cardiovascular risk factors increases
      susceptibility to vascular disease, which may create demand for surgical
      intervention. In our study, data collected by the American Association of Medical
      Colleges Physician Specialty Databook of 2012, the United States Census Bureau,
      and other nationwide organizations were referenced to calculate future changes in
      vascular surgeon supply and prevalence of people at risk for vascular disease. In
      2010, there were 2853 active vascular surgeons. By 2040, the workforce is
      expected to linearly rise to 3573. There will be an exponential rise in people
      with cardiovascular risk factors. Adding to concern, in 2030, an estimated 3333
      vascular surgeons will be available for 180,000,000 people with at least one risk
      factor for peripheral arterial disease. The paucity of properly trained surgeons
      entering the workforce needs to be addressed before this shortage becomes a
      larger burden on healthcare providers and governmental spending. 

PMID- 26199291
TI  - A comparative study of Toxoplasma gondii seroprevalence in mink using a modified
      agglutination test, a Western blot, and enzyme-linked immunosorbent assays.
AB  - Toxoplasma gondii can infect almost all warm-blooded animals, and many
      serological methods have been developed to detect T. gondii infection in a
      variety of animal species. In the present study, the seroprevalence of T. gondii
      infection in farmed mink in northeast China was determined using the modified
      agglutination test (MAT), a Western blot (WB), and 3 enzyme-linked immunosorbent
      assays (ELISAs) with protein A/G conjugate, using either of 2 recombinant dense
      granule antigens, GRA1 and GRA7, or Toxoplasma soluble antigens (TSA). There was
      no significant difference between the detection results of the GRA1-, GRA7-, and
      TSA-ELISAs and WB (McNemar chi-square, P > 0.05), but a significant difference
      was observed between MAT and WB (P < 0.05). A near perfect agreement (97.0%) was
      found between the GRA7-ELISA and WB (kappa = 0.83), and a substantial agreement
      (92.4-93.1%) was observed in the TSA- and GRA1-ELISAs (kappa = 0.68-0.73). The
      GRA7-ELISA showed the highest sensitivity and specificity, and the lowest false
      positive and negative rates, while the MAT gave both a low sensitivity and
      frequent false positives in comparison to the WB. Receiver operating
      characteristic analysis revealed the largest area under curve of 0.85 (95%
      confidence interval: 0.74-0.96), and the highest relative sensitivity (72.7%) and
      specificity (99.0%) for a cutoff value of 0.19 in the GRA7-ELISA. These results
      indicate that the GRA7-ELISA is suitable for detection of T. gondii infection in
      mink and that MAT should be used with caution. 

PMID- 26199294
TI  - Multicultural Nursing: Providing Better Employee Care.
AB  - Living in an increasingly multicultural society, nurses are regularly required to
      care for employees from a variety of cultural backgrounds. An awareness of
      cultural differences focuses occupational health nurses on those differences and
      results in better employee care. This article explores the concept of culturally
      competent employee care, some of the non-verbal communication cues among cultural
      groups, models associated with completing a cultural assessment, and how health
      disparities in the workplace can affect delivery of employee care. Self
      evaluation of the occupational health nurse for personal preferences and biases
      is also discussed. Development of cultural competency is a process, and
      occupational health nurses must develop these skills. By developing cultural
      competence, occupational health nurses can conduct complete cultural assessments,
      facilitate better communication with employees from a variety of cultural
      backgrounds, and improve employee health and compliance with care regimens. Tips
      and guidelines for facilitating communication between occupational health nurses
      and employees are also provided. 

PMID- 26199295
TI  - Treatment of wide-necked basilar tip aneurysm not amenable to Y-stenting using
      the PulseRider device.
AB  - Endovascular treatment of broad-necked bifurcation aneurysms remains challenging.
      Stent-assisted coiling has been successful but requires catheterization of the
      branches off the parent vessel. We present the case of a patient who failed
      primary and stent-assisted coiling of a large basilar tip aneurysm because the
      morphology of the aneurysm precluded successful distal catheterization of the
      posterior cerebral artery (PCA) branches. Using the PulseRider device, which does
      not require catheterization of bifurcation branches, we were able to treat the
      aneurysm successfully. 

PMID- 26199296
TI  - Neurosurgical management of a large meningocele in Jarcho-Levin syndrome:
      clinical and radiological pearls.

PMID- 26199297
TI  - Treatment of a dissecting vertebral artery aneurysm with angioplasty and the
      pipeline embolisation device.
AB  - A 49-year-old woman was admitted with Hunt and Hess grade 1 subarachnoid
      haemorrhage. A cerebral aneurysm of the intracranial left vertebral artery (VA)
      distal to the left posterior inferior cerebellar artery (PICA) was found and
      treated using parent vessel occlusion with coils. The PICA was preserved.
      Angiography at three time points during her hospitalisation showed a normal right
      VA. Eight months later, angiography demonstrated a new 14 mm right VA dissecting
      aneurysm with 90% outflow stenosis and recurrence of the left VA aneurysm distal
      to the coils. A Marksman microcatheter would not traverse the stenosis despite
      the use of two intraluminal wires. Following Gateway balloon (1.5 mm * 9 mm)
      angioplasty, the Marksman passed easily. The pipeline embolisation device (PED)
      was successfully deployed across the aneurysm and 11 coils placed through a
      trapped microcatheter. The patient was discharged home 2 days later. Eighteen
      month follow-up has revealed complete resolution of both aneurysms.

PMID- 26199298
TI  - Induced liver injury after high-dose methylprednisolone in a patient with
      multiple sclerosis.
AB  - A 33-year-old woman with multiple sclerosis, medicated with high doses of
      methylprednisolone, cyclophosphamide and glatiramer acetate, was referred to our
      department due to acute liver injury. The laboratory investigation was normal
      except for weakly positive antinuclear antibodies. Cyclophosphamide and
      glatiramer acetate were suspended, and intravenous immunoglobulin with
      maintenance of high doses of methylprednisolone was initiated. The patient
      developed another episode of acute hepatitis so the immunoglobulin was stopped.
      After that, she had three more episodes of elevation of liver enzymes with no
      hepatic insufficiency while medicated only with high doses of methylprednisolone.
      At this time, liver biopsy showed focal centrilobubar hepatocyte necrosis with
      minimal interface hepatitis. After the high doses of methylprednisolone were
      suspended, the patient remained asymptomatic, with normal hepatic enzymes. This
      case emphasises that, although rare, induced liver injury after high doses of
      methylprednisolone can occur. 

PMID- 26199299
TI  - Cutaneous Cryptococcus: marker for disseminated infection.
AB  - Cryptococcosis is an infection caused by the encapsulated yeast, Cryptococcus
      neoformans, a dimorphic fungus recovered from pigeon excreta, soil, dust and
      human skin. After a primary infection in the lungs, the disease can disseminate
      via a haematogenous route to various organs, including the central nervous system
      and skin, in susceptible individuals. Cryptococcosis can present with a variety
      of skin and soft tissue manifestations including acneiform lesions, purpura,
      vesicles, nodules, abscesses, ulcers, granulomas, pustules, draining sinuses and
      cellulitis. We present a case of a young man with HIV infection who developed
      molluscum-like cutaneous lesions secondary to pulmonary cryptococcosis. The
      diagnosis was confirmed by Indian ink preparation of the cutaneous lesions.
      Primary cutaneous infection occurs rarely due to direct inoculation. Cutaneous
      lesions are usually secondary and act as a key marker of disseminated infection,
      especially in patients with impaired cell-mediated immunity, such as those
      infected with HIV, solid-organ transplant recipients, and those on chronic
      corticosteroid therapy. 

PMID- 26199300
TI  - Perivascular spread of adenoid cystic carcinoma: a novel imaging sign.

PMID- 26199301
TI  - Laser treatment of macular retinoschisis due to acquired optic nerve pit from
      glaucoma.
AB  - Macular retinoschisis can be caused by acquired optic nerve pit from glaucoma.
      This study evaluated the efficacy of laser treatment for this disorder. We report
      on five eyes from three patients with macular retinoschisis and a history of
      glaucoma. Spectral domain optical coherence tomography was used for diagnosis and
      follow-up. Treatment was performed with barrier laser on the temporal margin of
      the optic nerve. Following treatment, patients' average vision improved by 1 line
      on the Snellen chart at average follow-up of 12.3 months. All five eyes showed
      significant improvement in macular retinoschisis. The tracts connecting the optic
      pit to the retinoschisis completely closed in three eyes and nearly closed in two
      eyes. These cases demonstrate that laser photocoagulation is an effective
      treatment of macular retinoschisis from acquired optic nerve pit. It can serve as
      first-line treatment before more invasive options such as vitrectomy are
      considered.

PMID- 26199303
TI  - Skull base injury with extensive pneumocephalus after transnasal endotracheal
      intubation.
AB  - Iatrogenic injuries of the frontal skull base commonly occur during endoscopic
      sinus surgery. In this paper, we present a rare case of cranial base injury after
      transnasal endotracheal intubation for dental surgery. A 61-year-old otherwise
      healthy man presented at the emergency department with headache, right leg
      weakness and watery nasal discharge on the left side. He underwent a dental
      surgery under general anaesthesia with transnasal endotracheal intubation 2 days
      earlier. A CT of the head showed a bone defect of the left skull base with a
      bifrontal pneumocephalus. Urgent endoscopic sinus surgery with exposure of the
      skull base was performed. The anterior part of the middle nasal turbinate was
      found dislocated and resulted in an injury of the lateral lamella of the
      cribriform plate. After endoscopic reconstruction of the bone defect, the patient
      showed a rapid improvement of symptoms. Two years after surgery the patient is
      free of symptoms.

PMID- 26199302
TI  - A case of De Garengeot hernia requiring early surgery.
AB  - De Garengeot hernia is a rare clinical entity defined as the presence of a
      vermiform appendix within a femoral hernia sac. A 50-year-old woman presented to
      the emergency department with a painful lump over her right groin region. A
      bedside ultrasound was performed and soft tissue lesion was suspected. CT was
      performed and revealed a swollen tubular structure with fat stranding within the
      mass. De Garengeot hernia with acute appendicitis was diagnosed preoperatively,
      and an emergency appendectomy and hernioplasty were performed. Although it is
      usually an incidental finding during hernioplasty, De Garengeot hernia should be
      considered in the differential diagnosis of patients with an incarcerated femoral
      hernia. Mesh repair can be performed depending on the clinical situation. We
      report a rare case of incarcerated femoral hernia with acute appendicitis that
      required early surgical management to avoid associated complications. 

PMID- 26199304
TI  - Adenocarcinoma of the lung presenting with massive subcutaneous emphysema.

PMID- 26199305
TI  - Weight change after 20 years of age and the incidence of dyslipidemia: a cohort
      study of Japanese male workers.
AB  - BACKGROUND: While heavier weight is known to increase the incidence of
      dyslipidemia, limited data are available on the relationship between weight gain
      and its development. METHODS: A total of 2647 males were categorized into the
      following four groups according to the difference between their self-reported
      weight at 20 years of age and their measured weight in 1994-95: a loss of >=5%
      (decrease), loss of <5% or gain of <5% (no change), gain of >=5 to <15%
      (increase) and gain of >=15% (sizable increase). They were followed up until
      their 2002-03 health examination. Using the 'no change' group as reference, the
      multivariable-adjusted odds ratio (adjusted for age, body mass index at 20 years
      of age, physical activity, smoking and alcohol intake) and 95% confidence
      interval (95% CI) for the incidence of dyslipidemia were determined using
      logistic regression models. RESULTS: A total of 1342 participants developed
      dyslipidemia during the follow-up period. The 'increase' and 'sizable increase'
      groups had odds ratios for the incidence of dyslipidemia of 1.97 (95% CI, 1.59
      2.45) and 2.68 (2.15-3.34), respectively, demonstrating that there was a
      significant dose-response association between weight gain since 20 years of age
      and the incidence of dyslipidemia (P < 0.001 for trend). CONCLUSION: These
      results suggest that dyslipidemia could be prevented by avoiding weight gain in
      adulthood.

PMID- 26199306
TI  - Forum for Early Career Clinical Investigation: New Section for Circulation: Heart
      Failure.

PMID- 26199307
TI  - Health Status and Incident Heart Failure in Chronic Kidney Disease: Accumulating
      Evidence to Use Patient-Reported Measures in Clinical Care.

PMID- 26199308
TI  - Glycemia Lowering and Risk for Heart Failure: Recent Evidence from Studies of
      Dipeptidyl Peptidase Inhibition.

PMID- 26199309
TI  - Contemporary Drug Development in Heart Failure: Call for Hemodynamically Neutral
      Therapies.

PMID- 26199310
TI  - Defying Dogma: Recovery After Left Ventricular Assist Device Implantation and
      Aortic Valve Replacement for Bicuspid Aortic Valve.

PMID- 26199311
TI  - Acute Orthotopic Heart Transplantation Rejection With ST-Segment Elevation in
      Leads I and aVL.

PMID- 26199312
TI  - Letter by Brutsaert and De Keulenaer Regarding Article, "Effects of Sildenafil on
      Ventricular and Vascular Function in Heart Failure With Preserved Ejection
      Fraction".

PMID- 26199313
TI  - Correction.

PMID- 26199314
TI  - Role of Acute Lesion Topography in Initial Ischemic Stroke Severity and Long-Term
      Functional Outcomes.
AB  - BACKGROUND AND PURPOSE: Acute infarct volume, often proposed as a biomarker for
      evaluating novel interventions for acute ischemic stroke, correlates only
      moderately with traditional clinical end points, such as the modified Rankin
      Scale. We hypothesized that the topography of acute stroke lesions on diffusion
      weighted magnetic resonance imaging may provide further information with regard
      to presenting stroke severity and long-term functional outcomes. METHODS: Data
      from a prospective stroke repository were limited to acute ischemic stroke
      subjects with magnetic resonance imaging completed within 48 hours from last
      known well, admission NIH Stroke Scale (NIHSS), and 3-to-6 months modified Rankin
      Scale scores. Using voxel-based lesion symptom mapping techniques, including age,
      sex, and diffusion-weighted magnetic resonance imaging lesion volume as
      covariates, statistical maps were calculated to determine the significance of
      lesion location for clinical outcome and admission stroke severity. RESULTS: Four
      hundred ninety subjects were analyzed. Acute stroke lesions in the left
      hemisphere were associated with more severe NIHSS at admission and poor modified
      Rankin Scale at 3 to 6 months. Specifically, injury to white matter (corona
      radiata, internal and external capsules, superior longitudinal fasciculus, and
      uncinate fasciculus), postcentral gyrus, putamen, and operculum were implicated
      in poor modified Rankin Scale. More severe NIHSS involved these regions, as well
      as the amygdala, caudate, pallidum, inferior frontal gyrus, insula, and
      precentral gyrus. CONCLUSIONS: Acute lesion topography provides important
      insights into anatomic correlates of admission stroke severity and poststroke
      outcomes. Future models that account for infarct location in addition to
      diffusion-weighted magnetic resonance imaging volume may improve stroke outcome
      prediction and identify patients likely to benefit from aggressive acute
      intervention and personalized rehabilitation strategies.

PMID- 26199315
TI  - Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With
      Long-Term Mortality.
AB  - BACKGROUND AND PURPOSE: Total homocysteine (tHcy) levels are associated with
      secondary vascular events and mortality after stroke. The aim of this study was
      to investigate whether tHcy levels in the acute phase of a stroke contribute to
      the recurrence of cerebro-cardiovascular events and mortality. METHODS: A total
      of 3799 patients were recruited after hospital admission for acute ischemic
      stroke. Levels of tHcy were measured within 24 hours after primary admission.
      Patients were followed for a median of 48 months. RESULTS: During the follow-up
      period, 233 (6.1%) patients died. After adjustment for age, smoking status,
      diabetes mellitus, and other cardiovascular risk factors, patients in the highest
      tHcy quartile (>18.6 MUmol/L) had a 1.61-fold increased risk of death (adjusted
      hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03-2.53) compared with
      patients in the lowest quartile (<=10 MUmol/L). Further subgroup analysis showed
      that this correlation was only significant in the large-artery atherosclerosis
      stroke subtype (adjusted HR, 1.80; 95% CI, 1.05-3.07); this correlation was not
      significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI,
      0.30-2.12). The risk of stroke-related mortality was 2.27-fold higher for
      patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06-4.86) and
      2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95%
      CI, 1.01-4.63) than for patients in the lowest tHcy quartile. The risk of
      cardiovascular-related mortality and the risk of recurrent ischemic stroke were
      not associated with tHcy levels. CONCLUSIONS: Our findings suggest that elevated
      tHcy levels in the acute phase of an ischemic stroke can predict mortality,
      especially in stroke patients with the large-vessel atherosclerosis subtype.

PMID- 26199316
TI  - Neuronal copper homeostasis susceptibility by genetic defects in dysbindin, a
      schizophrenia susceptibility factor.
AB  - Environmental factors and susceptible genomes interact to determine the risk of
      neurodevelopmental disorders. Although few genes and environmental factors have
      been linked, the intervening cellular and molecular mechanisms connecting a
      disorder susceptibility gene with environmental factors remain mostly unexplored.
      Here we focus on the schizophrenia susceptibility gene DTNBP1 and its product
      dysbindin, a subunit of the BLOC-1 complex, and describe a neuronal pathway
      modulating copper metabolism via ATP7A. Mutations in ATP7A result in Menkes
      disease, a disorder of copper metabolism. Dysbindin/BLOC-1 and ATP7A genetically
      and biochemically interact. Furthermore, disruption of this pathway causes
      alteration in the transcriptional profile of copper-regulatory and dependent
      factors in the hippocampus of dysbindin/BLOC-1-null mice. Dysbindin/BLOC-1 loss
      of-function alleles do not affect cell and tissue copper content, yet they alter
      the susceptibility to toxic copper challenges in both mammalian cells and
      Drosophila. Our results demonstrate that perturbations downstream of the
      schizophrenia susceptibility gene DTNBP1 confer susceptibility to copper, a metal
      that in excess is a neurotoxin and whose depletion constitutes a micronutrient
      deficiency. 

PMID- 26199317
TI  - Structural basis of glycogen branching enzyme deficiency and pharmacologic rescue
      by rational peptide design.
AB  - Glycogen branching enzyme 1 (GBE1) plays an essential role in glycogen
      biosynthesis by generating alpha-1,6-glucosidic branches from alpha-1,4-linked
      glucose chains, to increase solubility of the glycogen polymer. Mutations in the
      GBE1 gene lead to the heterogeneous early-onset glycogen storage disorder type IV
      (GSDIV) or the late-onset adult polyglucosan body disease (APBD). To better
      understand this essential enzyme, we crystallized human GBE1 in the apo form, and
      in complex with a tetra- or hepta-saccharide. The GBE1 structure reveals a
      conserved amylase core that houses the active centre for the branching reaction
      and harbours almost all GSDIV and APBD mutations. A non-catalytic binding cleft,
      proximal to the site of the common APBD mutation p.Y329S, was found to bind the
      tetra- and hepta-saccharides and may represent a higher-affinity site employed to
      anchor the complex glycogen substrate for the branching reaction. Expression of
      recombinant GBE1-p.Y329S resulted in drastically reduced protein yield and
      solubility compared with wild type, suggesting this disease allele causes protein
      misfolding and may be amenable to small molecule stabilization. To explore this,
      we generated a structural model of GBE1-p.Y329S and designed peptides ab initio
      to stabilize the mutation. As proof-of-principle, we evaluated treatment of one
      tetra-peptide, Leu-Thr-Lys-Glu, in APBD patient cells. We demonstrate
      intracellular transport of this peptide, its binding and stabilization of GBE1
      p.Y329S, and 2-fold increased mutant enzymatic activity compared with untreated
      patient cells. Together, our data provide the rationale and starting point for
      the screening of small molecule chaperones, which could become novel therapies
      for this disease. 

PMID- 26199318
TI  - Pyridoxamine and pyridoxal are more effective than pyridoxine in rescuing folding
      defective variants of human alanine:glyoxylate aminotransferase causing primary
      hyperoxaluria type I.
AB  - Vitamin B6 in the form of pyridoxine (PN) is one of the most widespread
      pharmacological therapies for inherited diseases involving pyridoxal phosphate
      (PLP)-dependent enzymes, including primary hyperoxaluria type I (PH1). PH1 is
      caused by a deficiency of liver-peroxisomal alanine: glyoxylate aminotransferase
      (AGT), which allows glyoxylate oxidation to oxalate leading to the deposition of
      insoluble calcium oxalate in the kidney. Only a minority of PH1 patients, mostly
      bearing the F152I and G170R mutations, respond to PN, the only pharmacological
      treatment currently available. Moreover, excessive doses of PN reduce the
      specific activity of AGT in a PH1 cellular model. Nevertheless, the possible
      effect(s) of other B6 vitamers has not been investigated previously. Here, we
      compared the ability of PN in rescuing the effects of the F152I and G170R
      mutations with that of pyridoxamine (PM) and PL. We found that supplementation
      with PN raises the intracellular concentration of PN phosphate (PNP), which
      competes with PLP for apoenzyme binding leading to the formation of an inactive
      AGT-PNP complex. In contrast, PNP does not accumulate in the cell upon PM or PL
      supplementation, but higher levels of PLP and PM phosphate (PMP), the two active
      forms of the AGT coenzyme, are found. This leads to an increased ability of PM
      and PL to rescue the effects of the F152I and G170R mutations compared with PN. A
      similar effect was also observed for other folding-defective AGT variants. Thus,
      PM and PL should be investigated as matter of importance as therapeutics for PH1
      patients bearing folding mutations. 

PMID- 26199319
TI  - Dynamin-2 mutations associated with centronuclear myopathy are hypermorphic and
      lead to T-tubule fragmentation.
AB  - Skeletal muscle requires adequate membrane trafficking and remodeling to maintain
      its normal structure and functions. Consequently, many human myopathies are
      caused by mutations in membrane trafficking machinery. The large GTPase dynamin-2
      (Dyn2) is best known for catalyzing membrane fission during clathrin-mediated
      endocytosis (CME), which is critical for cell signaling and survival. Despite its
      ubiquitous expression, mutations of Dyn2 are associated with two tissue-specific
      congenital disorders: centronuclear myopathy (CNM) and Charcot-Marie-Tooth (CMT)
      neuropathy. Several disease models for CNM-Dyn2 have been established to study
      its pathogenic mechanism; yet the cellular and biochemical effects of these
      mutations are still not fully understood. Here we comprehensively compared the
      biochemical activities of disease-associated Dyn2 mutations and found that CNM
      Dyn2 mutants are hypermorphic with enhanced membrane fission activity, whereas
      CMT-Dyn2 is hypomorphic. More importantly, we found that the expression of CNM
      Dyn2 mutants does not impair CME in myoblast, but leads to T-tubule fragmentation
      in both C2C12-derived myotubes and Drosophila body wall muscle. Our results
      demonstrate that CNM-Dyn2 mutants are gain-of-function mutations, and their
      primary effect in muscle is T-tubule disorganization, which explains the
      susceptibility of muscle to Dyn2 hyperactivity. 

PMID- 26199320
TI  - Low-frequency germline variants across 6p22.2-6p21.33 are associated with non
      obstructive azoospermia in Han Chinese men.
AB  - Genome-wide association studies (GWAS) have identified several common loci
      contributing to non-obstructive azoospermia (NOA). However, a substantial
      fraction of NOA heritability remains undefined, especially those low-frequency
      [defined here as having a minor allele frequency (MAF) between 0.5 and 5%] and
      rare (MAF below 0.5%) variants. Here, we performed a 3-stage exome-wide
      association study in Han Chinese men to evaluate the role of low-frequency or
      rare germline variants in NOA development. The discovery stage included 962 NOA
      cases and 1348 healthy male controls genotyped by exome chips and was followed by
      a 2-stage replication with an additional 2168 cases and 5248 controls. We
      identified three low-frequency variants located at 6p22.2 (rs2298090 in HIST1H1E
      encoding p.Lys152Arg: OR = 0.30, P = 2.40 * 10(-16)) and 6p21.33 (rs200847762 in
      FKBPL encoding p.Pro137Leu: OR = 0.11, P = 3.77 * 10(-16); rs11754464 in MSH5: OR
      = 1.78, P = 3.71 * 10(-7)) associated with NOA risk after Bonferroni correction.
      In summary, we report an instance of newly identified signals for NOA risk in
      genes previously undetected through GWAS on 6p22.2-6p21.33 in a Chinese
      population and highlight the role of low-frequency variants with a large effect
      in the process of spermatogenesis. 

PMID- 26199321
TI  - Exome sequencing reveals a nonsense mutation in TEX15 causing spermatogenic
      failure in a Turkish family.
AB  - Infertility is a global healthcare problem, and despite long years of assisted
      reproductive activities, a significant number of cases remain idiopathic. Our
      currently restricted understanding of basic mechanisms driving human
      gametogenesis severely limits the improvement of clinical care for infertile
      patients. Using exome sequencing, we identified a nonsense mutation leading to a
      premature stop in the TEX15 locus (c.2130T>G, p.Y710*) in a consanguineous
      Turkish family comprising eight siblings in which three brothers were identified
      as infertile. TEX15 displays testis-specific expression, maps to chromosome 8,
      contains four exons and encodes a 2789-amino acid protein with uncertain
      function. The mutation, which should lead to early translational termination at
      the first exon of TEX15, co-segregated with the infertility phenotype, and our
      data strongly suggest that it is the cause of spermatogenic defects in the
      family. All three affected brothers presented a phenotype reminiscent of the one
      observed in KO mice. Indeed, previously reported results demonstrated that
      disruption of the orthologous gene in mice caused a drastic reduction in testis
      size and meiotic arrest in the first wave of spermatogenesis in males while
      female KO mice were fertile. The data from our study of one Turkish family
      suggested that the identified mutation correlates with a decrease in sperm count
      over time. A diagnostic test identifying the mutation in man could provide an
      indication of spermatogenic failure and prompt patients to undertake sperm
      cryopreservation at an early age. 

PMID- 26199323
TI  - Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis.
AB  - RATIONALE: The development of molecular imaging approaches that assess specific
      immunopathologic mechanisms can advance the study of myocarditis. OBJECTIVE: This
      study validates a novel molecular imaging tool that enables the in vivo
      visualization of granzyme B activity, a major effector of cytotoxic CD8+ T
      lymphocytes. METHODS AND RESULTS: We synthesized and optimized a fluorogenic
      substrate capable of reporting on granzyme B activity and examined its
      specificity ex vivo in mice hearts with experimental cytotoxic CD8+ T lymphocyte
      mediated myocarditis using fluorescence reflectance imaging, validated by
      histological examination. In vivo experiments localized granzyme B activity in
      hearts with acute myocarditis monitored by fluorescent molecular tomography in
      conjunction with coregistered computed tomography imaging. A model anti
      inflammatory intervention (dexamethasone administration) in vivo reduced granzyme
      B activity (vehicle versus dexamethasone: 504+/-263 versus 194+/-77 fluorescence
      intensities in hearts; P=0.002). CONCLUSIONS: Molecular imaging of granzyme B
      activity can visualize T cell-mediated myocardial injury and monitor the response
      to an anti-inflammatory intervention.

PMID- 26199324
TI  - Fishing for Effective Conservation: Context and Biotic Variation are Keys to
      Understanding the Survival of Pacific Salmon after Catch-and-Release.
AB  - Acute stressors are commonly experienced by wild animals but their effects on
      fitness rarely are studied in the natural environment. Billions of fish are
      captured and released annually around the globe across all fishing sectors (e.g.,
      recreational, commercial, subsistence). Whatever the motivation, release often
      occurs under the assumption of post-release survival. Yet, capture by fisheries
      (hereafter "fisheries-capture") is likely the most severe acute stressor
      experienced in the animal's lifetime, which makes the problem of physiological
      recovery and survival of relevance to biology and conservation. Indeed, fisheries
      managers require accurate estimates of mortality to better account for total
      mortality from fishing, while fishers desire guidance on strategies for reducing
      mortality and maintaining the welfare of released fish, to maximize current and
      future opportunities for fishing. In partnership with stakeholders, our team has
      extensively studied the effects of catch-and-release on Pacific salmon in both
      marine and freshwater environments, using biotelemetry and physiological
      assessments in a combined laboratory-based and field-based approach. The emergent
      theme is that post-release rates of mortality are consistently context-specific
      and can be affected by a suite of interacting biotic and abiotic factors. The
      fishing gear used, location of a fishery, water temperature, and handling
      techniques employed by fishers each can dramatically affect survival of the
      salmon they release. Variation among individuals, co-migrating populations, and
      between sexes all seem to play a role in the response of fish to capture and in
      their subsequent survival, potentially driven by pre-capture pathogen-load,
      maturation states, and inter-individual variation in responsiveness to stress.
      Although some of these findings are fascinating from a biological perspective,
      they all create unresolved challenges for managers. We summarize our findings by
      highlighting the patterns that have emerged most consistently, and point to areas
      of uncertainty that require further research. 

PMID- 26199322
TI  - A local complement response by RPE causes early-stage macular degeneration.
AB  - Inherited and age-related macular degenerations (AMDs) are important causes of
      vision loss. An early hallmark of these disorders is the formation of sub-retinal
      pigment epithelium (RPE) basal deposits. A role for the complement system in MDs
      was suggested by genetic association studies, but direct functional connections
      between alterations in the complement system and the pathogenesis of MD remain to
      be defined. We used primary RPE cells from a mouse model of inherited MD due to a
      p.R345W mutation in EGF-containing fibulin-like extracellular matrix protein 1
      (EFEMP1) to investigate the role of the RPE in early MD pathogenesis.
      Efemp1(R345W) RPE cells recapitulate the basal deposit formation observed in vivo
      by producing sub-RPE deposits in vitro. The deposits share features with basal
      deposits, and their formation was mediated by EFEMP1(R345W) or complement
      component 3a (C3a), but not by complement component 5a (C5a). Increased
      activation of complement appears to occur in response to an abnormal
      extracellular matrix (ECM), generated by the mutant EFEMP1(R345W) protein and
      reduced ECM turnover due to inhibition of matrix metalloproteinase 2 by
      EFEMP1(R345W) and C3a. Increased production of C3a also stimulated the release of
      cytokines such as interleukin (IL)-6 and IL-1B, which appear to have a role in
      deposit formation, albeit downstream of C3a. These studies provide the first
      direct indication that complement components produced locally by the RPE are
      involved in the formation of basal deposits. Furthermore, these results suggest
      that C3a generated by RPE is a potential therapeutic target for the treatment of
      EFEMP1-associated MD as well as AMD. 

PMID- 26199325
TI  - Thermotolerant Yeast Strains Adapted by Laboratory Evolution Show Trade-Off at
      Ancestral Temperatures and Preadaptation to Other Stresses.
AB  - A major challenge for the production of ethanol from biomass-derived feedstocks
      is to develop yeasts that can sustain growth under the variety of inhibitory
      conditions present in the production process, e.g., high osmolality, high ethanol
      titers, and/or elevated temperatures (>= 40  degrees C). Using adaptive
      laboratory evolution, we previously isolated seven Saccharomyces cerevisiae
      strains with improved growth at 40  degrees C. Here, we show that genetic
      adaptations to high temperature caused a growth trade-off at ancestral
      temperatures, reduced cellular functions, and improved tolerance of other
      stresses. Thermotolerant yeast strains showed horizontal displacement of their
      thermal reaction norms to higher temperatures. Hence, their optimal and maximum
      growth temperatures increased by about 3  degrees C, whereas they showed a growth
      trade-off at temperatures below 34  degrees C. Computational analysis of the
      physical properties of proteins showed that the lethal temperature for yeast is
      around 49  degrees C, as a large fraction of the yeast proteins denature above
      this temperature. Our analysis also indicated that the number of functions
      involved in controlling the growth rate decreased in the thermotolerant strains
      compared with the number in the ancestral strain. The latter is an advantageous
      attribute for acquiring thermotolerance and correlates with the reduction of
      yeast functions associated with loss of respiration capacity. This trait caused
      glycerol overproduction that was associated with the growth trade-off at
      ancestral temperatures. In combination with altered sterol composition of
      cellular membranes, glycerol overproduction was also associated with yeast
      osmotolerance and improved tolerance of high concentrations of glucose and
      ethanol. Our study shows that thermal adaptation of yeast is suitable for
      improving yeast resistance to inhibitory conditions found in industrial ethanol
      production processes. IMPORTANCE: Yeast thermotolerance can significantly reduce
      the production costs of biomass conversion to ethanol. However, little
      information is available about the underlying genetic changes and physiological
      functions required for yeast thermotolerance. We recently revealed the genetic
      changes of thermotolerance in thermotolerant yeast strains (TTSs) generated
      through adaptive laboratory evolution. Here, we examined these TTSs' physiology
      and computed their proteome stability over the entire thermal niche, as well as
      their preadaptation to other stresses. Using this approach, we showed that TTSs
      exhibited evolutionary trade-offs in the ancestral thermal niche, as well as
      reduced numbers of growth functions and preadaptation to other stresses found in
      ethanol production processes. This information will be useful for rational
      engineering of yeast thermotolerance for the production of biofuels and
      chemicals.

PMID- 26199326
TI  - Mapping the Evolution of Hypervirulent Klebsiella pneumoniae.
AB  - Highly invasive, community-acquired Klebsiella pneumoniae infections have
      recently emerged, resulting in pyogenic liver abscesses. These infections are
      caused by hypervirulent K. pneumoniae (hvKP) isolates primarily of capsule
      serotype K1 or K2. Hypervirulent K1 isolates belong to clonal complex 23 (CC23),
      indicating that this clonal lineage has a specific genetic background conferring
      hypervirulence. Here, we apply whole-genome sequencing to a collection of K.
      pneumoniae isolates to characterize the phylogenetic background of hvKP isolates
      with an emphasis on CC23. Most of the hvKP isolates belonged to CC23 and grouped
      into a distinct monophyletic clade, revealing that CC23 is a unique clonal
      lineage, clearly distinct from nonhypervirulent strains. Separate phylogenetic
      analyses of the CC23 isolates indicated that the CC23 lineage evolved recently by
      clonal expansion from a single common ancestor. Limited grouping according to
      geographical origin was observed, suggesting that CC23 has spread globally
      through multiple international transmissions. Conversely, hypervirulent K2
      strains clustered in genetically unrelated groups. Strikingly, homologues of a
      large virulence plasmid were detected in all hvKP clonal lineages, indicating a
      key role in K. pneumoniae hypervirulence. The plasmid encodes two siderophores,
      aerobactin and salmochelin, and RmpA (regulator of the mucoid phenotype); all
      these factors were found to be restricted to hvKP isolates. Genomic comparisons
      revealed additional factors specifically associated with CC23. These included a
      distinct variant of a genomic island encoding yersiniabactin, colibactin, and
      microcin E492. Furthermore, additional novel genomic regions unique to CC23 were
      revealed which may also be involved in the increased virulence of this important
      clonal lineage. IMPORTANCE: During the last 3 decades, hypervirulent Klebsiella
      pneumoniae (hvKP) isolates have emerged, causing severe community-acquired
      infections primarily in the form of pyogenic liver abscesses. This syndrome has
      so far primarily been found in Southeast Asia, but increasing numbers of cases
      are being reported worldwide, indicating that the syndrome is turning into a
      globally emerging disease. We applied whole-genome sequencing to a collection of
      K. pneumoniae clinical isolates to reveal the phylogenetic background of hvKP and
      to identify genetic factors associated with the increased virulence. The hvKP
      isolates primarily belonged to clonal complex 23 (CC23), and this clonal lineage
      was revealed to be clearly distinct from nonhypervirulent strains. A specific
      virulence plasmid was found to be associated with hypervirulence, and novel
      genetic determinants uniquely associated with CC23 were identified. Our findings
      extend the understanding of the genetic background of the emergence of hvKP
      clones.

PMID- 26199327
TI  - CRISPR-Cas9-Mediated Genome Editing in Leishmania donovani.
AB  - The prokaryotic CRISPR (clustered regularly interspaced short palindromic repeat)
      Cas9, an RNA-guided endonuclease, has been shown to mediate efficient genome
      editing in a wide variety of organisms. In the present study, the CRISPR-Cas9
      system has been adapted to Leishmania donovani, a protozoan parasite that causes
      fatal human visceral leishmaniasis. We introduced the Cas9 nuclease into L.
      donovani and generated guide RNA (gRNA) expression vectors by using the L.
      donovani rRNA promoter and the hepatitis delta virus (HDV) ribozyme. It is
      demonstrated within that L. donovani mainly used homology-directed repair (HDR)
      and microhomology-mediated end joining (MMEJ) to repair the Cas9 nuclease-created
      double-strand DNA break (DSB). The nonhomologous end-joining (NHEJ) pathway
      appears to be absent in L. donovani. With this CRISPR-Cas9 system, it was
      possible to generate knockouts without selection by insertion of an
      oligonucleotide donor with stop codons and 25-nucleotide homology arms into the
      Cas9 cleavage site. Likewise, we disrupted and precisely tagged endogenous genes
      by inserting a bleomycin drug selection marker and GFP gene into the Cas9
      cleavage site. With the use of Hammerhead and HDV ribozymes, a double-gRNA
      expression vector that further improved gene-targeting efficiency was developed,
      and it was used to make precise deletion of the 3-kb miltefosine transporter gene
      (LdMT). In addition, this study identified a novel single point mutation caused
      by CRISPR-Cas9 in LdMT (M381T) that led to miltefosine resistance, a concern for
      the only available oral antileishmanial drug. Together, these results demonstrate
      that the CRISPR-Cas9 system represents an effective genome engineering tool for
      L. donovani. IMPORTANCE: Leishmania donovani is the causative agent of fatal
      visceral leishmaniasis. To understand Leishmania infection and pathogenesis and
      identify new drug targets for control of leishmaniasis, more-efficient ways to
      manipulate this parasite genome are required. In this study, we have implemented
      CRISPR-Cas9 genome-editing technology in L. donovani. Both single- and dual-gRNA
      expression vectors were developed using a strong RNA polymerase I promoter and
      ribozymes. With this system, it was possible to generate loss-of-function
      insertion and deletion mutations and introduce drug selection markers and the GFP
      sequence precisely into the L. donovani genome. These methods greatly improved
      the ability to manipulate this parasite genome and will help pave the way for
      high-throughput functional analysis of Leishmania genes. This study further
      revealed that double-stranded DNA breaks created by CRISPR-Cas9 were repaired by
      the homology-directed repair (HDR) pathway and microhomology-mediated end joining
      (MMEJ) in Leishmania.

PMID- 26199328
TI  - Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation
      in Salmonella enterica.
AB  - In Salmonella enterica, the reversible lysine acetylation (RLA) system is
      comprised of the protein acetyltransferase (Pat) and sirtuin deacetylase (CobB).
      RLA controls the activities of many proteins, including the acetyl coenzyme A
      (acetyl-CoA) synthetase (Acs), by modulating the degree of Acs acetylation. We
      report that IolR, a myo-inositol catabolism repressor, activates the expression
      of genes encoding components of the RLA system. In vitro evidence shows that the
      IolR protein directly regulates pat expression. An iolR mutant strain displayed a
      growth defect in minimal medium containing 10 mM acetate, a condition under which
      RLA function is critical to control Acs activity. Increased levels of Pat, CobB,
      or Acs activity reversed the growth defect, suggesting the Pat/CobB ratio in an
      iolR strain is altered and that such a change affects the level of acetylated,
      inactive Acs. Results of quantitative reverse transcription-PCR (qRT-PCR)
      analyses of pat, cobB, and acs expression indicated that expression of the genes
      alluded to in the IolR-deficient strain was reduced 5-, 3-, and 2.6-fold,
      respectively, relative to the levels present in the strain carrying the iolR(+)
      allele. Acs activity in cell-free extracts from an iolR mutant strain was reduced
      ~25% relative to that of the iolR(+) strain. Glucose differentially regulated
      expression of pat, cobB, and acs. The catabolite repressor protein (Crp)
      positively regulated expression of pat while having no effect on cobB.
      IMPORTANCE: Reversible lysine acylation is used by cells of all domains of life
      to modulate the function of proteins involved in diverse cellular processes. Work
      reported herein begins to outline the regulatory circuitry that integrates the
      expression of genes encoding enzymes that control the activity of a central
      metabolic enzyme in C2 metabolism. Genetic analyses revealed effects on
      reversible lysine acylation that greatly impacted the growth behavior of the
      cell. This work provides the first insights into the complexities of the system
      responsible for controlling reversible lysine acylation at the transcriptional
      level in the enteropathogenic bacterium Salmonella enterica.

PMID- 26199330
TI  - A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux
      Sensing Mechanism.
AB  - Sensing of and responding to environmental changes are of vital importance for
      microbial cells. Consequently, bacteria have evolved a plethora of signaling
      systems that usually sense biochemical cues either via direct ligand binding,
      thereby acting as "concentration sensors," or by responding to downstream effects
      on bacterial physiology, such as structural damage to the cell. Here, we describe
      a novel, alternative signaling mechanism that effectively implements a "flux
      sensor" to regulate antibiotic resistance. It relies on a sensory complex
      consisting of a histidine kinase and an ABC transporter, in which the transporter
      fulfills the dual role of both the sensor of the antibiotic and the mediator of
      resistance against it. Combining systems biological modeling with in vivo
      experimentation, we show that these systems in fact respond to changes in
      activity of individual resistance transporters rather than to changes in the
      antibiotic concentration. Our model shows that the cell thereby adjusts the rate
      of de novo transporter synthesis to precisely the level needed for protection.
      Such a flux-sensing mechanism may serve as a cost-efficient produce-to-demand
      strategy, controlling a widely conserved class of antibiotic resistance systems.
      IMPORTANCE: Bacteria have to be able to accurately perceive their environment to
      allow adaptation to changing conditions. This is usually accomplished by sensing
      the concentrations of beneficial or harmful substances or by measuring the effect
      of the prevailing conditions on the cell. Here we show the existence of a new way
      of sensing the environment, where the bacteria monitor the activity of an
      antibiotic resistance transporter. Such a "flux-sensing" mechanism allows the
      cell to detect its current capacity to deal with the antibiotic challenge and
      thus precisely respond to the need for more transporters. We propose that this is
      a cost-efficient way of regulating antibiotic resistance on demand.

PMID- 26199331
TI  - Erratum for Martin et al., Phylogenomic Identification of Regulatory Sequences in
      Bacteria: an Analysis of Statistical Power and an Application to Borrelia
      burgdorferi Sensu Lato.

PMID- 26199329
TI  - Genomics and Transcriptomics Analyses of the Oil-Accumulating Basidiomycete Yeast
      Trichosporon oleaginosus: Insights into Substrate Utilization and Alternative
      Evolutionary Trajectories of Fungal Mating Systems.
AB  - Microbial fermentation of agro-industrial waste holds great potential for
      reducing the environmental impact associated with the production of lipids for
      industrial purposes from plant biomass. However, the chemical complexity of many
      residues currently prevents efficient conversion into lipids, creating a high
      demand for strains with the ability to utilize all energy-rich components of
      agricultural residues. Here, we present results of genome and transcriptome
      analyses of Trichosporon oleaginosus. This oil-accumulating yeast is able to grow
      on a wide variety of substrates, including pentoses and N-acetylglucosamine,
      making it an interesting candidate for biotechnological applications.
      Transcriptomics shows specific changes in gene expression patterns under lipid
      accumulating conditions. Furthermore, gene content and expression analyses
      indicate that T. oleaginosus is well-adapted for the utilization of chitin-rich
      biomass. We also focused on the T. oleaginosus mating type, because this species
      is a member of the Tremellomycetes, a group that has been intensively analyzed as
      a model for the evolution of sexual development, the best-studied member being
      Cryptococcus neoformans. The structure of the T. oleaginosus mating-type regions
      differs significantly from that of other Tremellomycetes and reveals a new
      evolutionary trajectory paradigm. Comparative analysis shows that recruitment of
      developmental genes to the ancestral tetrapolar mating-type loci occurred
      independently in the Trichosporon and Cryptococcus lineages, supporting the
      hypothesis of a trend toward larger mating-type regions in fungi. IMPORTANCE:
      Finite fossil fuel resources pose sustainability challenges to society and
      industry. Microbial oils are a sustainable feedstock for biofuel and chemical
      production that does not compete with food production. We describe genome and
      transcriptome analyses of the oleaginous yeast Trichosporon oleaginosus, which
      can accumulate up to 70% of its dry weight as lipids. In contrast to conventional
      yeasts, this organism not only shows an absence of diauxic effect while
      fermenting hexoses and pentoses but also effectively utilizes xylose and N
      acetylglucosamine, which are building blocks of lignocellulose and chitin,
      respectively. Transcriptome analysis revealed metabolic networks that govern
      conversion of xylose or N-acetylglucosamine as well as lipid accumulation. These
      data form the basis for a targeted strain optimization strategy. Furthermore,
      analysis of the mating type of T. oleaginosus supports the hypothesis of a trend
      toward larger mating-type regions in fungi, similar to the evolution of sex
      chromosomes in animals and plants.

PMID- 26199332
TI  - Mucosal Immunization with Newcastle Disease Virus Vector Coexpressing HIV-1 Env
      and Gag Proteins Elicits Potent Serum, Mucosal, and Cellular Immune Responses
      That Protect against Vaccinia Virus Env and Gag Challenges.
AB  - Newcastle disease virus (NDV) avirulent strain LaSota was used to coexpress gp160
      Env and p55 Gag from a single vector to enhance both Env-specific and Gag
      specific immune responses. The optimal transcription position for both Env and
      Gag genes in the NDV genome was determined by generating recombinant NDV (rNDV)
      Env-Gag (gp160 located between the P and M genes and Gag between the HN and L
      genes), rNDV-Gag-Env (Gag located between the P and M genes and gp160 between the
      HN and L genes), rNDV-Env/Gag (gp160 followed by Gag located between the P and M
      genes), and rNDV-Gag/Env (Gag followed by gp160 located between the P and M
      genes). All the recombinant viruses replicated at levels similar to those seen
      with parental NDV in embryonated chicken eggs and in chicken fibroblast cells.
      Both gp160 and Gag proteins were expressed at high levels in cell culture, with
      gp160 found to be incorporated into the envelope of NDV. The Gag and Env proteins
      expressed by all the recombinants except rNDV-Env-Gag self-assembled into human
      immunodeficiency virus type 1 (HIV-1) virus-like particles (VLPs). Immunization
      of guinea pigs by the intranasal route with these rNDVs produced long-lasting Env
      and Gag-specific humoral immune responses. The Env-specific humoral and mucosal
      immune responses and Gag-specific humoral immune responses were higher in rNDV
      Gag/Env and rNDV-Env/Gag than in the other recombinants. rNDV-Gag/Env and rNDV
      Env/Gag were also more efficient in inducing cellular as well as protective
      immune responses to challenge with vaccinia viruses expressing HIV-1 Env and Gag
      in mice. These results suggest that vaccination with a single rNDV coexpressing
      Env and Gag represents a promising strategy to enhance immunogenicity and
      protective efficacy against HIV. IMPORTANCE: A safe and effective vaccine that
      can induce both systemic and mucosal immune responses is needed to control HIV-1.
      In this study, we showed that coexpression of Env and Gag proteins of HIV-1
      performed using a single Newcastle disease virus (NDV) vector led to the
      formation of HIV-1 virus-like particles (VLPs). Immunization of guinea pigs with
      recombinant NDVs (rNDVs) elicited potent long-lasting systemic and mucosal immune
      responses to HIV. Additionally, the rNDVs were efficient in inducing cellular
      immune responses to HIV and protective immunity to challenge with vaccinia
      viruses expressing HIV Env and Gag in mice. These results suggest that the use of
      a single NDV expressing Env and Gag proteins simultaneously is a novel strategy
      to develop a safe and effective vaccine against HIV.

PMID- 26199333
TI  - CRISPR/Cas9-Induced Disruption of Paraflagellar Rod Protein 1 and 2 Genes in
      Trypanosoma cruzi Reveals Their Role in Flagellar Attachment.
AB  - Trypanosoma cruzi is the etiologic agent of Chagas disease, and current methods
      for its genetic manipulation have been highly inefficient. We report here the use
      of the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9
      (CRISPR-associated gene 9) system for disrupting genes in the parasite by three
      different strategies. The utility of the method was established by silencing
      genes encoding the GP72 protein, which is required for flagellar attachment, and
      paraflagellar rod proteins 1 and 2 (PFR1, PFR2), key components of the parasite
      flagellum. We used either vectors containing single guide RNA (sgRNA) and Cas9,
      separately or together, or one vector containing sgRNA and Cas9 plus donor DNA
      for homologous recombination to rapidly generate mutant cell lines in which the
      PFR1, PFR2, and GP72 genes have been disrupted. We demonstrate that genome
      editing of these endogenous genes in T. cruzi is successful without detectable
      toxicity of Cas9. Our results indicate that PFR1, PFR2, and GP72 contribute to
      flagellar attachment to the cell body and motility of the parasites. Therefore,
      CRISPR/Cas9 allows efficient gene disruption in an almost genetically intractable
      parasite and suggest that this method will improve the functional analyses of its
      genome. IMPORTANCE: Trypanosoma cruzi is the agent of Chagas disease, which
      affects millions of people worldwide. Vaccines to prevent this disease are not
      available, and drug treatments are not completely effective. The study of the
      biology of this parasite through genetic approaches will make possible the
      development of new preventive or treatment options. Previous attempts to use the
      CRISPR/Cas9 in T. cruzi found a detectable but low frequency of Cas9-facilitated
      homologous recombination and fluorescent marker swap between exogenous genes,
      while Cas9 was toxic to the cells. In this report, we describe new approaches
      that generate complete disruption of an endogenous gene without toxicity to the
      parasites and establish the relevance of several proteins for flagellar
      attachment and motility.

PMID- 26199334
TI  - An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from Multiple
      Subtypes of Influenza A Virus.
AB  - Influenza virus infections are a global public health problem, with a significant
      impact of morbidity and mortality from both annual epidemics and pandemics. The
      current strategy for preventing annual influenza is to develop a new vaccine each
      year against specific circulating virus strains. Because these vaccines are
      unlikely to protect against an antigenically divergent strain or a new pandemic
      virus with a novel hemagglutinin (HA) subtype, there is a critical need for
      vaccines that protect against all influenza A viruses, a so-called "universal"
      vaccine. Here we show that mice were broadly protected against challenge with a
      wide variety of lethal influenza A virus infections (94% aggregate survival
      following vaccination) with a virus-like particle (VLP) vaccine cocktail. The
      vaccine consisted of a mixture of VLPs individually displaying H1, H3, H5, or H7
      HAs, and vaccinated mice showed significant protection following challenge with
      influenza viruses expressing 1918 H1, 1957 H2, and avian H5, H6, H7, H10, and H11
      hemagglutinin subtypes. These experiments suggest a promising and practical
      strategy for developing a broadly protective "universal" influenza vaccine.
      IMPORTANCE: The rapid and unpredictable nature of influenza A virus evolution
      requires new vaccines to be produced annually to match circulating strains. Human
      infections with influenza viruses derived from animals can cause outbreaks that
      may be associated with high mortality, and such strains may also adapt to humans
      to cause a future pandemic. Thus, there is a large public health need to create
      broadly protective, or "universal," influenza vaccines that could prevent disease
      from a wide variety of human and animal influenza A viruses. In this study, a
      noninfectious virus-like particle (VLP) vaccine was shown to offer significant
      protection against a variety of influenza A viruses in mice, suggesting a
      practical strategy to develop a universal influenza vaccine.

PMID- 26199335
TI  - Assessing and Managing the Risks of Potential Pandemic Pathogen Research.

PMID- 26199336
TI  - Correction for Osterholm et al., Transmission of Ebola Viruses: What We Know and
      What We Do Not Know.

PMID- 26199337
TI  - Impact of Institutional Volume on Outcomes of Catheter Directed Thrombolysis in
      the Treatment of Acute Proximal Deep Vein Thrombosis: A 6-Year US Experience
      (2005-2010).
AB  - BACKGROUND: The use of catheter-directed thrombolysis (CDT) in the treatment of
      acute proximal lower-extremity deep vein thrombosis is increasing in the United
      States and has been linked to higher bleeding rates. Whether this relationship is
      interrelated with institution volume of CDT is unknown. METHODS AND RESULTS: The
      Nationwide Inpatient Sample database was used to identify all patients admitted
      with a principal diagnosis of proximal or inferior vena caval deep vein
      thrombosis and treated with CDT from 2005 to 2010. Institutions were divided into
      high-volume (>=6 procedures a year) and low-volume (<6 procedures a year)
      centers. Propensity score matching was used to create 2 matched groups for
      comparative analysis. A total of 90 618 patients were hospitalized for proximal
      lower-extremity deep vein thrombosis, and 3649 patients (4.1%) underwent CDT. In
      hospital mortality was significantly lower at high-volume centers (0.6% versus
      1.5%; P=0.04) with a trend toward lower intracranial hemorrhage rates compared
      with low-volume centers (0.4% versus 1%; P=0.07). No significant difference was
      seen with blood transfusion (10.4% versus 10.8%; P=0.70), gastrointestinal
      bleeding (1.4% versus 1.8%; P=0.35), or pulmonary embolism rates (18.4% versus
      17.9%; P=0.72). Median length of stay was similar (6 days) and hospital charges
      were higher ($65 500 versus $75 870) at high-volume centers. CONCLUSIONS: In this
      observational study, we found that an increase in institutional volume of CDT was
      associated with lower in-hospital mortality and lower intracranial hemorrhage
      rates. Further studies are needed to assess whether standardization of CDT
      protocols across all institutions in the United States improves outcomes.

PMID- 26199338
TI  - Comparison of the short-term risk of bleeding and arterial thromboembolic events
      in nonvalvular atrial fibrillation patients newly treated with dabigatran or
      rivaroxaban versus vitamin K antagonists: a French nationwide propensity-matched
      cohort study.
AB  - BACKGROUND: The safety and effectiveness of non-vitamin K antagonist (VKA) oral
      anticoagulants, dabigatran or rivaroxaban, were compared with VKA in
      anticoagulant-naive patients with nonvalvular atrial fibrillation during the
      early phase of anticoagulant therapy. METHODS AND RESULTS: With the use of the
      French medico-administrative databases (SNIIRAM and PMSI), this nationwide cohort
      study included patients with nonvalvular atrial fibrillation who initiated
      dabigatran or rivaroxaban between July and November 2012 or VKA between July and
      November 2011. Patients presenting a contraindication to oral anticoagulants were
      excluded. Dabigatran and rivaroxaban new users were matched to VKA new users by
      the use of 1:2 matching on the propensity score. Patients were followed for up to
      90 days until outcome, death, loss to follow-up, or December 31 of the inclusion
      year. Hazard ratios of hospitalizations for bleeding and arterial thromboembolic
      events were estimated in an intent-to-treat analysis using Cox regression models.
      The population was composed of 19 713 VKA, 8443 dabigatran, and 4651 rivaroxaban
      new users. All dabigatran- and rivaroxaban-treated patients were matched to 16
      014 and 9301 VKA-treated patients, respectively. Among dabigatran-, rivaroxaban-,
      and their VKA-matched-treated patients, 55 and 122 and 31 and 68 bleeding events
      and 33 and 58 and 12 and 28 arterial thromboembolic events were observed during
      follow-up, respectively. After matching, no statistically significant difference
      in bleeding (hazard ratio, 0.88; 95% confidence interval, 0.64-1.21) or
      thromboembolic (hazard ratio, 1.10; 95% confidence interval, 0.72-1.69) risk was
      observed between dabigatran and VKA new users. Bleeding (hazard ratio, 0.98; 95%
      confidence interval, 0.64-1.51) and ischemic (hazard ratio, 0.93; 95% confidence
      interval, 0.47-1.85) risks were comparable between rivaroxaban and VKA new users.
      CONCLUSIONS: In this propensity-matched cohort study, our findings suggest that
      physicians should exercise caution when initiating either non-VKA oral
      anticoagulants or VKA in patients with nonvalvular atrial fibrillation.

PMID- 26199339
TI  - Genome-wide Gene-Asbestos Exposure Interaction Association Study Identifies a
      Common Susceptibility Variant on 22q13.31 Associated with Lung Cancer Risk.
AB  - BACKGROUND: Occupational asbestos exposure has been found to increase lung cancer
      risk in epidemiologic studies. METHODS: We conducted an asbestos exposure-gene
      interaction analyses among several Caucasian populations who were current or ex
      smokers. The discovery phase included 833 Caucasian cases and 739 Caucasian
      controls, and used a genome-wide association study (GWAS) to identify single
      nucleotide polymorphisms (SNP) with gene-asbestos interaction effects. The top
      ranked SNPs from the discovery phase were replicated within the International
      Lung and Cancer Consortium (ILCCO). First, in silico replication was conducted in
      those groups that had GWAS and asbestos exposure data, including 1,548 cases and
      1,527 controls. This step was followed by de novo genotyping to replicate the
      results from the in silico replication, and included 1,539 cases and 1,761
      controls. Multiple logistic regression was used to assess the SNP-asbestos
      exposure interaction effects on lung cancer risk. RESULTS: We observed
      significantly increased lung cancer risk among MIRLET7BHG (MIRLET7B host gene
      located at 22q13.31) polymorphisms rs13053856, rs11090910, rs11703832, and
      rs12170325 heterozygous and homozygous variant allele(s) carriers (P < 5 * 10(-7)
      by likelihood ratio test; df = 1). Among the heterozygous and homozygous variant
      allele(s) carriers of polymorphisms rs13053856, rs11090910, rs11703832, and
      rs12170325, each unit increase in the natural log-transformed asbestos exposure
      score was associated with age-, sex-, smoking status, and center-adjusted ORs of
      1.34 [95% confidence interval (CI), 1.18-1.51], 1.24 (95% CI, 1.14-1.35), 1.28
      (95% CI, 1.17-1.40), and 1.26 (95% CI, 1.15-1.38), respectively, for lung cancer
      risk. CONCLUSION: Our findings suggest that MIRLET7BHG polymorphisms may be
      important predictive markers for asbestos exposure-related lung cancer. IMPACT:
      To our knowledge, our study is the first report using a systematic genome-wide
      analysis in combination with detailed asbestos exposure data and replication to
      evaluate asbestos-associated lung cancer risk.

PMID- 26199340
TI  - Racial and Ethnic Disparity in Symptomatic Breast Cancer Awareness despite a
      Recent Screen: The Role of Tumor Biology and Mammography Facility
      Characteristics.
AB  - BACKGROUND: In a racially and ethnically diverse sample of recently diagnosed
      urban patients with breast cancer, we examined associations of patient, tumor
      biology, and mammography facility characteristics on the probability of
      symptomatic discovery of their breast cancer despite a recent prior screening
      mammogram. METHODS: In the Breast Cancer Care in Chicago study, self-reports at
      interview were used to define patients as having a screen-detected breast cancer
      or having symptomatic awareness despite a recent screening mammogram (SADRS), in
      the past 1 or 2 years. Patients with symptomatic breast cancer who did not report
      a recent prior screen were excluded from these analyses. Characteristics
      associated with more aggressive disease [estrogen receptor (ER)- and progesterone
      receptor (PR)-negative status and higher tumor grade] were abstracted from
      medical records. Mammogram facility characteristics that might indicate aspects
      of screening quality were defined and controlled for in some analyses. RESULTS:
      SADRS was more common among non-Hispanic black and Hispanic than among non
      Hispanic white patients (36% and 42% vs. 25%, respectively, P = 0.0004). SADRS
      was associated with ER/PR-negative and higher-grade disease. Patients screened at
      sites that relied on dedicated radiologists and sites that were breast imaging
      centers of excellence were less likely to report SADRS. Tumor and facility
      factors together accounted for two thirds of the disparity in SADRS (proportion
      mediated = 70%, P = 0.02). CONCLUSION: Facility resources and tumor
      aggressiveness explain much of the racial/ethnic disparity in symptomatic breast
      cancer among recently screened patients. IMPACT: A more equitable distribution of
      high-quality screening would ameliorate but not eliminate this disparity.

PMID- 26199341
TI  - Validation of a Stability-Indicating Method for Methylseleno-L-Cysteine (L-SeMC).
AB  - Methylseleno-L-cysteine (L-SeMC) is a naturally occurring amino acid analogue
      used as a general dietary supplement and is being explored as a chemopreventive
      agent. As a known dietary supplement, L-SeMC is not regulated as a pharmaceutical
      and there is a paucity of analytical methods available. To address the lack of
      methodology, a stability-indicating method was developed and validated to
      evaluate L-SeMC as both the bulk drug and formulated drug product (400 ug
      Se/capsule). The analytical approach presented is a simple, nonderivatization
      method that utilizes HPLC with ultraviolet detection at 220 nm. A C18 column with
      a volatile ion-pair agent and methanol mobile phase was used for the separation.
      The method accuracy was 99-100% from 0.05 to 0.15 mg/mL L-SeMC for the bulk drug,
      and 98-99% from 0.075 to 0.15 mg/mL L-SeMC for the drug product. Method precision
      was <1% for the bulk drug and was 3% for the drug product. The LOQ was 0.1 ug/mL
      L-SeMC or 0.002 ug L-SeMC on column.

PMID- 26199342
TI  - Identification of a Set of Conserved Eukaryotic Internal Retention Time Standards
      for Data-independent Acquisition Mass Spectrometry.
AB  - Accurate knowledge of retention time (RT) in liquid chromatography-based mass
      spectrometry data facilitates peptide identification, quantification, and
      multiplexing in targeted and discovery-based workflows. Retention time prediction
      is particularly important for peptide analysis in emerging data-independent
      acquisition (DIA) experiments such as SWATH-MS. The indexed RT approach, iRT,
      uses synthetic spiked-in peptide standards (SiRT) to set RT to a unit-less scale,
      allowing for normalization of peptide RT between different samples and
      chromatographic set-ups. The obligatory use of SiRTs can be costly and
      complicates comparisons and data integration if standards are not included in
      every sample. Reliance on SiRTs also prevents the inclusion of archived mass
      spectrometry data for generation of the peptide assay libraries central to
      targeted DIA-MS data analysis. We have identified a set of peptide sequences that
      are conserved across most eukaryotic species, termed Common internal Retention
      Time standards (CiRT). In a series of tests to support the appropriateness of the
      CiRT-based method, we show: (1) the CiRT peptides normalized RT in human, yeast,
      and mouse cell lysate derived peptide assay libraries and enabled merging of
      archived libraries for expanded DIA-MS quantitative applications; (2) CiRTs
      predicted RT in SWATH-MS data within a 2-min margin of error for the majority of
      peptides; and (3) normalization of RT using the CiRT peptides enabled the
      accurate SWATH-MS-based quantification of 340 synthetic isotopically labeled
      peptides that were spiked into either human or yeast cell lysate. To automate and
      facilitate the use of these CiRT peptide lists or other custom user-defined
      internal RT reference peptides in DIA workflows, an algorithm was designed to
      automatically select a high-quality subset of datapoints for robust linear
      alignment of RT for use. Implementations of this algorithm are available for the
      OpenSWATH and Skyline platforms. Thus, CiRT peptides can be used alone or as a
      complement to SiRTs for RT normalization across peptide spectral libraries and in
      quantitative DIA-MS studies. 

PMID- 26199343
TI  - Targeted Proteomics-Driven Computational Modeling of Macrophage S1P Chemosensing.
AB  - Osteoclasts are monocyte-derived multinuclear cells that directly attach to and
      resorb bone. Sphingosine-1-phosphate (S1P)(1) regulates bone resorption by
      functioning as both a chemoattractant and chemorepellent of osteoclast precursors
      through two G-protein coupled receptors that antagonize each other in an S1P
      concentration-dependent manner. To quantitatively explore the behavior of this
      chemosensing pathway, we applied targeted proteomics, transcriptomics, and rule
      based pathway modeling using the Simmune toolset. RAW264.7 cells (a mouse
      monocyte/macrophage cell line) were used as model osteoclast precursors, RNA-seq
      was used to identify expressed target proteins, and selected reaction monitoring
      (SRM) mass spectrometry using internal peptide standards was used to perform
      absolute abundance measurements of pathway proteins. The resulting transcript and
      protein abundance values were strongly correlated. Measured protein abundance
      values, used as simulation input parameters, led to in silico pathway behavior
      matching in vitro measurements. Moreover, once model parameters were established,
      even simulated responses toward stimuli that were not used for parameterization
      were consistent with experimental findings. These findings demonstrate the
      feasibility and value of combining targeted mass spectrometry with pathway
      modeling for advancing biological insight. 

PMID- 26199345
TI  - Multiphasic disseminated encephalomyelitis followed by optic neuritis in a child
      with gluten sensitivity.
AB  - Multiphasic disseminated encephalomyelitis (MDEM) followed by optic neuritis (ON)
      has been described as a new entity in recent years. Gluten encephalopathy has
      also been recognized as a neurological manifestation of celiac disease. Accurate
      diagnosis of both is important due to the therapeutic implications. We report a
      girl presenting with recurrent encephalopathic polyfocal demyelinating episodes
      followed by optic neuritis, and a clinical history suggestive of gluten
      sensitivity. She had persistently high ESR, neutrophilia, and tested positive for
      anti-MOG (myelin oligodendrocyte glycoprotein) antibody. She responded well to
      methylprednisolone in each relapse, and achieved remission for a year after
      azathioprine was added. 

PMID- 26199344
TI  - Quantitative Proteomics Reveals the Essential Roles of Stromal Interaction
      Molecule 1 (STIM1) in the Testicular Cord Formation in Mouse Testis.
AB  - Testicular cord formation in male gonadogenesis involves assembly of several cell
      types, the precise molecular mechanism is still not well known. With the high
      throughput quantitative proteomics technology, a comparative proteomic profile of
      mouse embryonic male gonads were analyzed at three time points (11.5, 12.5, and
      13.5 days post coitum), corresponding to critical stages of testicular cord
      formation in gonadal development. 4070 proteins were identified, and 338 were
      differentially expressed, of which the Sertoli cell specific genes were
      significant enrichment, with mainly increased expression across testis cord
      development. Additionally, we found overrepresentation of proteins related to
      oxidative stress in these Sertoli cell specific genes. Of these differentially
      expressed oxidative stress-associated Sertoli cell specific protein, stromal
      interaction molecule 1, was found to have discrepant mRNA and protein
      regulations, with increased protein expression but decreased mRNA levels during
      testis cord development. Knockdown of Stim1 in Sertoli cells caused extensive
      defects in gonadal development, including testicular cord disruption, loss of
      interstitium, and failed angiogenesis, together with increased levels of reactive
      oxygen species. And suppressing the aberrant elevation of reactive oxygen species
      could partly rescue the defects of testicular cord development. Taken together,
      our results suggest that reactive oxygen species regulation in Sertoli cells is
      important for gonadogenesis, and the quantitative proteomic data could be a rich
      resource to the elucidation of regulation of testicular cord development. 

PMID- 26199346
TI  - Comment on multiphasic disseminated encephalomyelitis followed by optic neuritis
      in a child with gluten sensitivity.

PMID- 26199348
TI  - Validation of kappa free light chains as a diagnostic biomarker in multiple
      sclerosis and clinically isolated syndrome: A multicenter study.
AB  - BACKGROUND: Kappa free light chains (KFLCs) have been proposed as a diagnostic
      biomarker in patients with clinically isolated syndrome (CIS) and multiple
      sclerosis (MS). OBJECTIVE: The objective of this paper is to validate the
      diagnostic accuracy of intrathecal KFLC synthesis in a multicenter study.
      METHODS: KFLCs were measured by nephelometry under blinded conditions in
      cerebrospinal fluid (CSF) and serum sample pairs of patients with CIS (n = 60),
      MS (n = 60) and other neurological diseases (n = 60) from four different MS
      centers. The upper normal limit for intrathecal KFLC concentrations depending on
      blood-CSF barrier function was previously calculated in a cohort of 420 control
      patients. RESULTS: Diagnostic sensitivity of intrathecal KFLC synthesis, IgG
      synthesis according to Reiber, IgG index and oligoclonal bands (OCBs) was 95%,
      72%, 73% and 93% in patients with MS and 82%, 47%, 43% and 72% in patients with
      CIS. Specificity of intrathecal KFLC synthesis was 95% and 98% for all other
      measures. CONCLUSION: These findings further support the diagnostic value of
      intrathecal KFLC synthesis in CIS and MS patients and demonstrate a valid, easier
      and rater-independent alternative to OCB detection.

PMID- 26199347
TI  - The effect of oral immunomodulatory therapy on treatment uptake and persistence
      in multiple sclerosis.
AB  - OBJECTIVE: We aimed to analyse the effect of the introduction of fingolimod, the
      first oral disease-modifying therapy, on treatment utilisation and persistence in
      an international cohort of patients with multiple sclerosis (MS). METHODS:
      MSBASIS, a prospective, observational sub-study of the MSBase registry, collects
      demographic, clinical and paraclinical data on patients followed from MS onset
      (n=4718). We conducted a multivariable conditional risk set survival analysis to
      identify predictors of treatment discontinuation, and to assess if the
      introduction of fingolimod has altered treatment persistence. RESULTS: A total of
      2640 patients commenced immunomodulatory therapy. Following the introduction of
      fingolimod, patients were more likely to discontinue all other treatments (hazard
      ratio 1.64, p<0.001) while more patients switched to fingolimod than any other
      therapy (42.3% of switches). Patients switched to fingolimod due to convenience.
      Patients treated with fingolimod were less likely to discontinue treatment
      compared with other therapies (p<0.001). Female sex, country of residence,
      younger age, a high Expanded Disability Status Scale score and relapse activity
      were all independently associated with higher rates of treatment discontinuation.
      CONCLUSION: Following the availability of fingolimod, patients were more likely
      to discontinue injectable treatments. Those who switched to fingolimod were more
      likely to do so for convenience. Persistence was improved on fingolimod compared
      to other medications.

PMID- 26199349
TI  - Population attributable fractions and joint effects of key risk factors for
      multiple sclerosis.
AB  - AIM: We examined the combined effect of having multiple key risk factors and the
      interactions between the key risk factors of multiple sclerosis (MS). METHODS: We
      performed an incident case-control study including cases with a first clinical
      diagnosis of central nervous system demyelination (FCD) and population-based
      controls. RESULTS: Compared to those without any risk factors, those with one,
      two, three, and four or five risk factors had increased odds of being an FCD case
      of 2.12 (95% confidence interval (CI), 1.11-4.03), 4.31 (95% CI, 2.24-8.31), 7.96
      (95% CI, 3.84-16.49), and 21.24 (95% CI, 5.48-82.40), respectively. Only HLA-DR15
      and history of infectious mononucleosis interacted significantly on the additive
      scale (Synergy index, 3.78; p = 0.03). The five key risk factors jointly
      accounted for 63.8% (95% CI, 43.9-91.4) of FCD onset. High anti-EBNA IgG was
      another important contributor. CONCLUSIONS: A high proportion of FCD onset can be
      explained by the currently known risk factors, with HLA-DR15, ever smoking and
      low cumulative sun exposure explaining most. We identified a significant
      interaction between HLA-DR15 and history of IM in predicting an FCD of CNS
      demyelination, which together with previous observations suggests that this is a
      true interaction.

PMID- 26199350
TI  - Neuromyelitis optica spectrum disorders: long-term safety and efficacy of
      rituximab in Caucasian patients.
AB  - OBJECTIVE: To assess the long-term benefit-risk profile of repeated courses of
      rituximab in Caucasian patients affected by neuromyelitis optica (NMO) and
      related disorders, in everyday clinical practice. METHODS: This is a prospective
      observational study performed at San Raffaele Hospital, Milan, Italy. From
      February 2006, we recruited 21 patients affected by NMO and NMO spectrum of
      disorders (NMOSD) whom underwent at least one cycle of intravenous (i.v.)
      rituximab and then were followed for at least 2 years. RESULTS: At a mean follow
      up time of 48 months, we observed a significant reduction of the annualized
      relapse rate (ARR), from 2.0 to 0.16 (p < 0.01); and of the median Expanded
      Disability Status Scale (EDSS), from 5.5 to 4.0 (p < 0.013). There were 12
      patients (57%) who remained disease free during the follow-up period. Five
      patients (24%) reported mild hematological adverse events. Serious infectious
      adverse events were reported by another four patients: These were all wheelchair
      bound at the beginning of their rituximab treatment. CONCLUSIONS: A fixed
      treatment scheme of rituximab, with re-treatment every 6 months, was efficacious
      for NMO and NMOSD, with a good safety profile; however, to obtain an even better
      benefit-risk ratio, close monitoring of CD19(+) B cells should be performed
      before the re-treatment of patients with high-level disability, concomitant
      leukopenia and hypogammaglobulinemia.

PMID- 26199351
TI  - Genetic burden mirrors epidemiology of multiple sclerosis.

PMID- 26199352
TI  - Fatal toxic epidermal necrolysis in a patient on teriflunomide treatment for
      relapsing multiple sclerosis.
AB  - We report a case of toxic epidermal necrolysis in a 46-year-old woman on
      teriflunomide treatment. Such a severe adverse cutaneous drug reaction with this
      new therapy for relapsing forms of multiple sclerosis should be early recognized
      in order to ensure the rapid withdrawal of the drug. 

PMID- 26199353
TI  - Assessing PML risk under immunotherapy: if all you have is a hammer, everything
      looks like a nail.
AB  - Recently, three progressive multifocal leukoencephalopathy (PML) cases have been
      reported in multiple sclerosis (MS) patients, two treated with fingolimod
      (Gilenya, Novartis), the third with dimethyl fumarate (Tecfidera, Biogen).
      Because our immunotherapeutic arsenal in MS and other diseases is increasing, and
      because PML is a very serious health risk, it is of interest to the clinical
      community to show how we can assess this risk in a statistically sound way. The
      null-hypothesis for this analysis was that there is no elevated risk for PML in
      patients treated with one of these recent drugs, compared to the incidence in the
      general population. We conclude that the null hypothesis cannot be refuted. 

PMID- 26199354
TI  - Intractable cough as characteristic symptom of neuromyelitis optica and
      neuromyelitis optica spectrum disorder.

PMID- 26199355
TI  - Diffusion tensor magnetic resonance imaging in very early onset pediatric
      multiple sclerosis.
AB  - OBJECTIVES: Active myelination during childhood may influence the impact of
      multiple sclerosis (MS) on brain structural integrity. We studied normal
      appearing white matter (NAWM) in children with MS onset before age 12 years using
      diffusion tensor (DT) magnetic resonance imaging (MRI). METHODS: DT MRI scans
      were obtained from 22 MS children with their first attack before age 12 years,
      and 31 healthy controls from two referral centers. Using probabilistic
      tractography, brain tissue integrity within interhemispheric, intrahemispheric,
      and projection tracts was compared between patients and site-matched controls.
      The impact of disease and age at MRI on tract NAWM fractional anisotropy (FA) and
      mean diffusivity (MD) values was evaluated using linear models. RESULTS: Compared
      to controls, pediatric MS patients had reduced FA and increased MD of the
      bilateral superior longitudinal fasciculus and corpus callosum (CC), without
      center-by-group interaction. CC NAWM average FA was correlated with brain T2
      lesion volume. In controls, the majority of the tracts analyzed showed a
      significant increase of FA and decrease of MD with age. Such a linear correlation
      was lost in patients. CONCLUSIONS: In very young pediatric MS patients, DT MRI
      abnormalities affect brain WM tracts differentially, and are only partially
      correlated with focal WM lesions. Impaired maturation of WM tracts with age may
      be an additional factor contributing to these findings.

PMID- 26199356
TI  - Viral exposures and MS outcome in a prospective cohort of children with acquired
      demyelination.
AB  - Epstein-Barr virus (EBV) infection is associated with increased multiple
      sclerosis (MS) risk. Recently, cytomegalovirus (CMV) infection has been proposed
      as a protective factor against MS development. We determined EBV, herpes simplex
      virus, varicella-zoster virus and CMV seroprevalence in 247 prospectively
      followed children with acquired demyelinating syndromes (ADS). Remote EBV
      infection was more common in children with MS than those with monophasic ADS
      while CMV infection was more common in children with monophasic ADS. Children
      displaying evidence of remote EBV without CMV infection were at highest risk of
      subsequent MS diagnosis. Viral infection repertoire detected at ADS provides
      important prognostic information. 

PMID- 26199359
TI  - Looking to the future of conservation genetics: The case for using quantitative
      genetic experiments to estimate the ability of rare plants to withstand climate
      change.

PMID- 26199357
TI  - Facile Discovery of Cell-Surface Protein Targets of Cancer Cell Aptamers.
AB  - Cancer biomarker discovery constitutes a frontier in cancer research. In recent
      years, cell-binding aptamers have become useful molecular probes for biomarker
      discovery. However, there are few successful examples, and the critical barrier
      resides in the identification of the cell-surface protein targets for the
      aptamers, where only a limited number of aptamer targets have been identified so
      far. Herein, we developed a universal SILAC-based quantitative proteomic method
      for target discovery of cell-binding aptamers. The method allowed for
      distinguishing specific aptamer-binding proteins from nonspecific proteins based
      on abundance ratios of proteins bound to aptamer-carrying bait and control bait.
      In addition, we employed fluorescently labeled aptamers for monitoring and
      optimizing the binding conditions. We were able to identify and validate selectin
      L and integrin alpha4 as the protein targets for two previously reported
      aptamers, Sgc-3b and Sgc-4e, respectively. This strategy should be generally
      applicable for the discovery of protein targets for other cell-binding aptamers,
      which will promote the applications of these aptamers. 

PMID- 26199360
TI  - Tempo and mode of flower color evolution.
AB  - * PREMISE OF THE STUDY: Flower color is one of the best-studied floral traits in
      terms of its genetic basis and ecological significance, yet few studies have
      examined the processes that shape its evolution across deep timescales. Advances
      in comparative methods along with larger phylogenies for floral radiations offer
      new opportunities for investigating the macroevolution of flower color.* METHODS:
      We examined the tempo and mode of flower color evolution in four clades
      (Antirrhineae, Iochrominae, Loeselieae, Quamoclit) using models that incorporate
      trait transitions and lineage diversification. Focusing on floral anthocyanin
      pigmentation, we estimated rates of gain and loss of pigmentation and tested
      whether these changes occur predominantly through anagenesis or cladogenesis.*
      KEY RESULTS: We found that the tempo of pigment gains and losses varied
      significantly across the clades and that the rates of change were often
      asymmetrical, favoring gains over losses. The mode of color shifts tended to be
      cladogenetic, particularly for gains of color; however, this trend was not
      significant.* CONCLUSIONS: Given that all flowering plants share the same pathway
      for producing anthocyanins, the marked variation in the tempo of transitions
      across the four groups suggests differences in the selective forces acting on
      floral pigmentation. These ecological and physiological factors, together with
      genetic basis for color, may also explain the bias toward gains of floral
      anthocyanins. Estimates for cladogenetic and anagenetic rates suggest that color
      transitions can occur through both modes, although testing their relative
      importance will require larger datasets.

PMID- 26199361
TI  - Contrasting models of the female reproductive tract in four o'clocks
      (Nyctaginaceae).
AB  - * PREMISE OF THE STUDY: In angiosperms, several carpel tissues are specialized to
      facilitate pollen-tube elongation to achieve fertilization. We evaluated the
      possible evolutionary pathways of the diverse female reproductive tracts in
      Nyctaginaceae.* METHODS: We studied the anatomy of a range of species
      representing different tribes, using light, fluorescence, scanning electron, and
      transmission electron microscopy.* KEY RESULTS: Stigmas have multicellular,
      multiseriate papillae, except for Boerhavia diffusa with unicellular papillae.
      The styles are solid, with a strand of transmitting tissue linking the stigma
      with the ventral ovary wall. In Allionia, Boerhavia, and Mirabilis, the
      transmitting tissue branches into two independent tracts at the base of the ovary
      and continues across the lateral margins of the funicle to the micropyle; it is
      composed of cells with thick walls surrounded by abundant extracellular matrix.
      Bougainvillea, Pisonia, and Pisoniella have a diffuse transmitting tissue and an
      obturator, a proliferation of cells covered by a layer of secretory papillae that
      encloses the funicle, placenta, and ventral wall of the gynoecium and contacts
      with the micropyle.* CONCLUSIONS: We propose two models of female reproductive
      tract, (A) one in which an obturator is absent and the transmitting tissue is
      compact and branched and (B) one in which an obturator is present and the
      transmitting tissue is diffuse. On the basis of character optimization, we
      hypothesize that model B represents the ancestral (plesiomorphic) condition in
      the family and model A originated once during evolution, within the tribe
      Nyctagineae.

PMID- 26199362
TI  - Adventitious root primordia formation and development in stem nodes of 'Georgia
      Jet' sweetpotato, Ipomoea batatas.
AB  - * PREMISE OF THE STUDY: Yield in sweetpotato is determined by the number of
      storage roots produced per plant. Storage roots develop from adventitious roots
      (ARs) present in stem cuttings that serve as propagation material. Data on the
      origin of sweetpotato ARs and the effect of nodal position on AR establishment
      and further development are limited.* METHODS: We anatomically described root
      primordium initiation using stem sections and measured number of root primordia
      formed at different nodal positions using light microscopy and correlated nodal
      positions with AR number and length 14 d after planting (DAP).* KEY RESULTS:
      Primordia for ARs initiate at the junction of the stem pith ray and the cambium,
      on both sides of the leaf gap, and they are well developed before emerging from
      the stem. The number of ARs that develop from isolated stem nodes 14 DAP
      corresponded to the number of AR primordia detected inside the stem. The total
      length of established roots at nodes 9-13 from the apex is about 2-fold longer
      than at nodes 5-8.* CONCLUSIONS: Nodal position (age) has a significant effect on
      the developmental status and number of root primordia inside the stem,
      determining the number and length of ARs that have developed by 14 DAP.
      Adventitious roots originating from nodes 9-13 possess similar AR systems and
      develop better than those originating from younger nodes 3-8. The mechanism
      regulating AR initiation in nodes is discussed. This system can serve for
      studying the effect of environmental conditions on AR initiation, development,
      and capacity to form storage roots.

PMID- 26199363
TI  - The role of root development of Avena fatua in conferring soil strength.
AB  - * PREMISE OF THE STUDY: Roots play an important role in strengthening and
      stabilizing soils. Existing models predict that tensile strength and root
      abundance are primary factors that strengthen soil. This study quantified how
      both factors are affected by root developmental stage.* METHODS: Focusing on
      early development of Avena fatua, a common grassland species with a fibrous root
      system, we chose three developmental stages associated with major changes in the
      root system. Seeds were planted in rhizotrons for easy viewing and pots to allow
      root growth surrounded by soil. Tensile strength was determined by subjecting
      root segments to a progressively larger pulling force until breaking occurred.
      Root abundance at two depths was characterized by the cross-sectional area of the
      roots divided by the area of the soil core (i.e., root area ratio). Shear
      strength of 50 mm saturated soil columns was determined with a modified interface
      direct shear device.* KEY RESULTS: Tensile strength increased by a factor of
      >=15* with distance from the root tip. Thus, soil-strengthening properties
      increased with root cell development. Plants grown under dry soil conditions
      produced roots with higher maximal tensile strength (41.9 MPa vs. approximately
      17 MPa), largely explained by 33% thinner diameters. Over 7 weeks of root growth,
      root abundance increased by a factor of 4.8* while saturated soil shear strength
      increased by 24% in the upper soil layer.* CONCLUSIONS: Root development should
      be incorporated into models of soil stability to improve understanding of this
      important environmental property.

PMID- 26199365
TI  - Environmental niche variation and evolutionary diversification of the
      Brachypodium distachyon grass complex species in their native circum
      Mediterranean range.
AB  - * PREMISE OF THE STUDY: We conducted environmental niche modeling (ENM) of the
      Brachypodium distachyon s.l. complex, a model group of two diploid annual grasses
      (B. distachyon, B. stacei) and their derived allotetraploid (B. hybridum), native
      to the circum-Mediterranean region. We (1) investigated the ENMs of the three
      species in their native range based on present and past climate data; (2)
      identified potential overlapping niches of the diploids and their hybrid across
      four Quaternary windows; (3) tested whether speciation was associated with niche
      divergence/conservatism in the complex species; and (4) tested for the potential
      of the polyploid outperforming the diploids in the native range.* METHODS: Geo
      referenced data, altitude, and 19 climatic variables were used to construct the
      ENMs. We used paleoclimate niche models to trace the potential existence of
      ancestral gene flow among the hybridizing species of the complex.* KEY RESULTS:
      Brachypodium distachyon grows in higher, cooler, and wetter places, B. stacei in
      lower, warmer, and drier places, and B. hybridum in places with intermediate
      climatic features. Brachypodium hybridum had the largest niche overlap with its
      parent niches, but a similar distribution range and niche breadth.* CONCLUSIONS:
      Each species had a unique environmental niche though there were multiple niche
      overlapping areas for the diploids across time, suggesting the potential
      existence of several hybrid zones during the Pleistocene and the Holocene. No
      evidence of niche divergence was found, suggesting that species diversification
      was not driven by ecological speciation but by evolutionary history, though it
      could be associated to distinct environmental adaptations.

PMID- 26199364
TI  - Spatiotemporal features of microsporogenesis in the cycad species Macrozamia
      communis.
AB  - * PREMISE OF THE STUDY: Spatiotemporal features of microsporogenesis may provide
      important clues about the evolution of microsporogenesis in seed plants. One
      cellular feature that attracts special attention is advance cell wall ingrowths
      (ACWIs) at future cytokinetic sites in microsporocytes since they have been found
      only in species of an ancient lineage of angiosperms, Magnolia, and in much less
      detail, of an ancient lineage of gymnosperms, cycads. Further investigation into
      microsporogenesis in a cycad species may yield knowledge critical to
      understanding the establishment of ACWIs as an important feature for comparative
      studies of microsporogenesis in seed plants.* METHODS: Bright-field and
      epifluorescence microscopy, confocal laser scanning microscopy, and transmission
      electron microscopy were used to investigate the microsporogenic process in
      Macrozamia communis, a species in the Zamiaceae family of cycads.* KEY RESULTS:
      In prophase-II microsporocytes in M. communis, ACWIs form as a callose ring
      between the newly formed nuclei and are not accompanied by cytokinetic
      apparatuses such as mini-phragmoplasts, wide tubules, or wide tubular networks.
      Shortly after the second nuclear division, new ACWIs, albeit thinner than the
      previous ACWIs, form between the newly formed nuclei. Subsequent cell plate
      formation in the planes of the ACWIs typically results in tetragonal tetrads.*
      CONCLUSIONS: Cytokinesis at the cell periphery is initiated earlier than cell
      plate formation in the cell interior in microsporogenesis in M. communis. The
      cellular features uncovered in M. communis may serve as useful reference features
      for comparative studies of microsporogenesis in plants.

PMID- 26199367
TI  - Phylogenetic congruence of parasitic smut fungi (Anthracoidea, Anthracoideaceae)
      and their host plants (Carex, Cyperaceae): Cospeciation or host-shift speciation?
AB  - * PREMISE OF THE STUDY: Fahrenholz's rule states that common ancestors of extant
      parasites were parasites of the common ancestors of extant hosts. Consequently,
      parasite phylogeny should mirror host phylogeny. The smut fungi genus
      Anthracoidea (Anthracoideaceae) is mainly hosted by species of the genus Carex
      (Cyperaceae). Whether smut fungi phylogeny mirrors sedge phylogeny is still under
      debate.* METHODS: The nuclear large subunit DNA region (LSU; 57 accessions) from
      31 Anthracoidea species and the ITS, ETS, and trnL-F spacer-trnL intron complex
      from 41 Carex species were used to infer the phylogenetic history of parasites
      and their hosts using a maximum likelihood approach. Event-based and distance
      based cophylogenetic methods were used to test the hypothesis of whether the
      phylogeny of smut fungi from the genus Anthracoidea matches the phylogeny of the
      sedge Carex species they host.* RESULTS: Cophylogenetic reconstructions taking
      into account phylogenetic uncertainties based on event-based analyses
      demonstrated that the Anthracoidea phylogeny has significant topological
      congruence with the phylogeny of their Carex hosts. A distance-based test was
      also significant; therefore, the phylogenies of Anthracoide and Carex are
      partially congruent.* CONCLUSIONS: The phylogenetic congruence of Anthracoidea
      and Carex is partially based on smut fungi species being preferentially hosted by
      closely related sedges (host conservatism). In addition, many different events
      rather than only codivergence events are inferred. All of this evidence suggests
      that host-shift speciation rather than cospeciation seems to explain the
      cophylogenetic patterns of Anthracoidea and Carex.

PMID- 26199366
TI  - The evolutionary history of ferns inferred from 25 low-copy nuclear genes.
AB  - * PREMISE OF THE STUDY: Understanding fern (monilophyte) phylogeny and its
      evolutionary timescale is critical for broad investigations of the evolution of
      land plants, and for providing the point of comparison necessary for studying the
      evolution of the fern sister group, seed plants. Molecular phylogenetic
      investigations have revolutionized our understanding of fern phylogeny, however,
      to date, these studies have relied almost exclusively on plastid data.* METHODS:
      Here we take a curated phylogenomics approach to infer the first broad fern
      phylogeny from multiple nuclear loci, by combining broad taxon sampling (73 ferns
      and 12 outgroup species) with focused character sampling (25 loci comprising
      35877 bp), along with rigorous alignment, orthology inference and model
      selection.* KEY RESULTS: Our phylogeny corroborates some earlier inferences and
      provides novel insights; in particular, we find strong support for Equisetales as
      sister to the rest of ferns, Marattiales as sister to leptosporangiate ferns, and
      Dennstaedtiaceae as sister to the eupolypods. Our divergence-time analyses reveal
      that divergences among the extant fern orders all occurred prior to ~200 MYA.
      Finally, our species-tree inferences are congruent with analyses of concatenated
      data, but generally with lower support. Those cases where species-tree support
      values are higher than expected involve relationships that have been supported by
      smaller plastid datasets, suggesting that deep coalescence may be reducing
      support from the concatenated nuclear data.* CONCLUSIONS: Our study demonstrates
      the utility of a curated phylogenomics approach to inferring fern phylogeny, and
      highlights the need to consider underlying data characteristics, along with data
      quantity, in phylogenetic studies.

PMID- 26199368
TI  - Exceptional reduction of the plastid genome of saguaro cactus (Carnegiea
      gigantea): Loss of the ndh gene suite and inverted repeat.
AB  - * PREMISE OF THE STUDY: Land-plant plastid genomes have only rarely undergone
      significant changes in gene content and order. Thus, discovery of additional
      examples adds power to tests for causes of such genome-scale structural changes.*
      METHODS: Using next-generation sequence data, we assembled the plastid genome of
      saguaro cactus and probed the nuclear genome for transferred plastid genes and
      functionally related nuclear genes. We combined these results with available data
      across Cactaceae and seed plants more broadly to infer the history of gene loss
      and to assess the strength of phylogenetic association between gene loss and loss
      of the inverted repeat (IR).* KEY RESULTS: The saguaro plastid genome is the
      smallest known for an obligately photosynthetic angiosperm (~113 kb), having lost
      the IR and plastid ndh genes. This loss supports a statistically strong
      association across seed plants between the loss of ndh genes and the loss of the
      IR. Many nonplastid copies of plastid ndh genes were found in the nuclear genome,
      but none had intact reading frames; nor did three related nuclear-encoded
      subunits. However, nuclear pgr5, which functions in a partially redundant
      pathway, was intact.* CONCLUSIONS: The existence of an alternative pathway
      redundant with the function of the plastid NADH dehydrogenase-like complex (NDH)
      complex may permit loss of the plastid ndh gene suite in photoautotrophs like
      saguaro. Loss of these genes may be a recurring mechanism for overall plastid
      genome size reduction, especially in combination with loss of the IR.

PMID- 26199369
TI  - Phylogeny, systematics, and trait evolution of Carex section Glareosae.
AB  - * PREMISE OF THE STUDY: The circumboreal Carex section Glareosae comprises 20-25
      currently accepted species. High variability in geographic distribution, ecology,
      cytogenetics, and morphology has led to historical problems both in species
      delimitation and in circumscribing the limits of the section, which is one of the
      major tasks facing caricologists today.* METHODS: We performed phylogenetic
      reconstructions based on ETS, ITS, G3PDH, and matK DNA sequences from 204
      samples. Concatenation of gene regions in a supermatrix approach to phylogenetic
      reconstruction was compared to coalescent-based species-tree estimation.
      Ancestral state reconstructions were performed for eight morphological characters
      to evaluate correspondence between phylogeny and traits used in traditional
      classification within the section.* KEY RESULTS: The results confirm the
      existence of a core Glareosae comprising 23-25 species. Most species constitute
      exclusive lineages, and relationships among species are highly resolved with both
      the supermatrix and coalescent-based species-tree approaches. We used ancestral
      state reconstruction to investigate sources of homoplasy underlying traditional
      taxonomy and species circumscription. We found that even species apparently not
      constituting exclusive lineages are morphologically homogeneous, raising the
      question of whether paraphyly of species is a phylogenetic artifact in our study
      or evidence of widespread homoplasy in characters used to define species.*
      CONCLUSIONS: This study demonstrates the monophyly of Carex section Glareosae and
      establishes a phylogenetic framework for the section. Homoplasy makes many of
      morphological characters difficult to apply for taxon delimitation. The strong
      concordance between supermatrix and species-tree approaches to phylogenetic
      reconstructions suggests that even in the face of incongruence among molecular
      markers, section-level or species-level phylogenies in Carex are tractable.

PMID- 26199370
TI  - Morphology delimits more species than molecular genetic clusters of invasive
      Pilosella.
AB  - * PREMISE OF THE STUDY: Accurate assessments of biodiversity are paramount for
      understanding ecosystem processes and adaptation to change. Invasive species
      often contribute substantially to local biodiversity; correctly identifying and
      distinguishing invaders is thus necessary to assess their potential impacts. We
      compared the reliability of morphology and molecular sequences to discriminate
      six putative species of invasive Pilosella hawkweeds (syn. Hieracium,
      Asteraceae), known for unreliable identifications and historical introgression.
      We asked (1) which morphological traits dependably discriminate putative species,
      (2) if genetic clusters supported morphological species, and (3) if novel
      hybridizations occur in the invaded range.* METHODS: We assessed 33 morphometric
      characters for their discriminatory power using the randomForest classifier and,
      using AFLPs, evaluated genetic clustering with the program structure and
      subsequently with an AMOVA. The strength of the association between morphological
      and genotypic dissimilarity was assessed with a Mantel test.* KEY RESULTS:
      Morphometric analyses delimited six species while genetic analyses defined only
      four clusters. Specifically, we found (1) eight morphological traits could
      reliably distinguish species, (2) structure suggested strong genetic
      differentiation but for only four putative species clusters, and (3) genetic data
      suggest both novel hybridizations and multiple introductions have occurred.*
      CONCLUSIONS: (1) Traditional floristic techniques may resolve more species than
      molecular analyses in taxonomic groups subject to introgression. (2) Even within
      complexes of closely related species, relatively few but highly discerning
      morphological characters can reliably discriminate species. (3) By clarifying
      patterns of morphological and genotypic variation of invasive Pilosella, we lay
      foundations for further ecological study and mitigation.

PMID- 26199371
TI  - Resolving Australian analogs for an Eocene Patagonian paleorainforest using leaf
      size and floristics.
AB  - * PREMISE OF THE STUDY: The diverse early Eocene flora from Laguna del Hunco (LH)
      in Patagonia, Argentina has many nearest living relatives (NLRs) in Australasia
      but few in South America, indicating the differential survival of an ancient,
      trans-Antarctic rainforest biome. To better understand this significant
      biogeographic pattern, we used detailed comparisons of leaf size and floristics
      to quantify the legacy of LH across a large network of Australian rainforest-plot
      assemblages.* METHODS: We applied vein scaling, a new method for estimating the
      original areas of fragmented leaves. We then compared leaf size and floristics at
      LH with living Australian assemblages and tabulated the climates of those where
      NLRs occur, along with additional data on climatic ranges of "ex-Australian" NLRs
      that survive outside of Australia.* KEY RESULTS: Vein scaling estimated areas as
      accurately as leaf-size classes. Applying vein scaling to fossil fragments
      increased the grand mean area of LH by 450 mm(2), recovering more originally
      large leaves. The paleoflora has a majority of microphyll leaves, comparable to
      leaf litter in subtropical Australian forests, which also have the greatest
      floristic similarity to LH. Tropical Australian assemblages also share many taxa
      with LH, and ex-Australian NLRs mostly inhabit cool, wet montane habitats no
      longer present in Australia.* CONCLUSIONS: Vein scaling is valuable for improving
      the resolution of fossil leaf-size distributions by including fragmented
      specimens. The legacy of LH is evident not only in subtropical and tropical
      Australia but also in tropical montane Australasia and Southeast Asia, reflecting
      the disparate histories of surviving Gondwanan lineages.

PMID- 26199372
TI  - Environmental and genetic correlates of allocation to sexual reproduction in the
      circumpolar plant Bistorta vivipara.
AB  - * PREMISE OF THE STUDY: Sexual reproduction often requires more energy and time
      than clonal reproduction. In marginal arctic conditions, species that can
      reproduce both sexually and clonally dominate. Plants with this capacity may
      thrive because they can alter reproduction depending on environmental conditions.
      Bistorta vivipara is a circumpolar herb that predominately reproduces clonally,
      but certain environmental conditions promote higher investment in flowers (and
      possible sexual reproduction). Despite largely reproducing clonally, the herb has
      high levels of genetic variation, and the processes underlying this paradoxical
      pattern of variation remain unclear. Here we identified environmental factors
      associated with sexual investment and examined whether sexual reproduction is
      associated with higher levels of genetic variation.* METHODS: We sampled 20
      populations of B. vivipara across the high Arctic archipelago of Svalbard. In
      each population, we measured reproductive traits, environmental variables, and
      collected samples for genetic analyses. These samples permitted hypotheses to be
      tested regarding sexual investment and ecological and genetic correlates.* KEY
      RESULTS: Increased soil nitrogen and organic matter content and decreased
      elevation were positively associated with investment in flowers. Increased
      investment in flowers significantly correlated with more genotypes per
      population. Linkage disequilibrium was consistent with predominant clonality, but
      several populations showed higher genetic variation and lower differentiation
      than expected. There was no geographical genetic structure.* CONCLUSIONS: In B.
      vivipara, sexual investment is positively associated with habitat quality.
      Bistorta vivipara predominantly reproduces clonally, but occasional outcrossing,
      efficient clonal reproduction, and dispersal by bulbils can explain the
      considerable genetic variation and weak genetic structure in B. vivipara.

PMID- 26199373
TI  - Sexual dimorphism in floral longevity and flowering synchrony in relation to
      pollination and mating success in three dioecious Ilex species.
AB  - * PREMISE OF THE STUDY: Sexual floral dimorphism may have evolved under
      pollinator-mediated natural selection by which female and male functions are
      differently influenced. We hypothesized that mating success is differently
      influenced by display size between sexes, under which sexual dimorphism in
      flowering schedule has evolved in dioecious species.* METHODS: We examined sexual
      dimorphism in the total number of flowers per shoot, maximum daily display size,
      longevity of individual flowers, and flowering synchrony (maximum proportion of
      open flowers) in three dioecious Ilex species (I. pedunculosa, I. serrata, and I.
      crenata) whose female flowers are not smaller than male flowers. We compared
      pollinator response to natural variation of daily display size between sexes. We
      also examined the effect of display size on female and male success (fruit set
      and pollen deposition and removal).* KEY RESULTS: In the three species, male
      shoots produced significantly more flowers than female shoots did. Although
      female flowers lasted longer and opened more synchronously than male flowers,
      maximum daily display size was larger on male shoots than on female shoots. Fruit
      set was significantly pollen-limited in the field in all species. Pollen
      deposition and/or fruit set increased with female display size, whereas pollen
      removal decreased or was approximately constant with male display size in the
      three species.* CONCLUSIONS: We suggest that sexual dimorphism in floral
      longevity and flowering synchrony might enhance both female and male success in
      relation to the display size-mating success (pollinator attraction) association
      irrespective of flower size dimorphism.

PMID- 26199374
TI  - Chloroplast heterogeneity and historical admixture within the genus Malus.
AB  - * PREMISE OF THE STUDY: The genus Malus represents a unique and complex
      evolutionary context in which to study domestication. Several Malus species have
      provided novel alleles and traits to the cultivars. The extent of admixture among
      wild Malus species has not been well described, due in part to limited sampling
      of individuals within a taxon.* METHODS: Four chloroplast regions (1681 bp total)
      were sequenced and aligned for 412 Malus individuals from 30 species.
      Phylogenetic relationships were reconstructed using maximum parsimony. The
      distribution of chloroplast haplotypes among species was examined using
      statistical parsimony, phylogenetic trees, and a median-joining network.* KEY
      RESULTS: Chloroplast haplotypes are shared among species within Malus. Three
      major haplotype-sharing networks were identified. One includes species native to
      China, Western North America, as well as Malus domestica Borkh, and its four
      primary progenitor species: M. sieversii (Ledeb.) M. Roem., M. orientalis
      Uglitzk., M. sylvestris (L.) Mill., and M. prunifolia (Willd.) Borkh; another
      includes five Chinese Malus species, and a third includes the three Malus species
      native to Eastern North America.* CONCLUSIONS: Chloroplast haplotypes found in M.
      domestica belong to a single, highly admixed network. Haplotypes shared between
      the domesticated apple and its progenitors may reflect historical introgression
      or the retention of ancestral polymorphisms. Multiple individuals should be
      sampled within Malus species to reveal haplotype heterogeneity, if complex
      maternal contributions to named species are to be recognized.

PMID- 26199375
TI  - Synonymous Genetic Variation in Natural Isolates of Escherichia coli Does Not
      Predict Where Synonymous Substitutions Occur in a Long-Term Experiment.
AB  - Synonymous genetic differences vary by more than 20-fold among genes in natural
      isolates of Escherichia coli. One hypothesis to explain this heterogeneity is
      that genes with high levels of synonymous variation mutate at higher rates than
      genes with low synonymous variation. If so, then one would expect to observe
      similar mutational patterns in evolution experiments. In fact, however, the
      pattern of synonymous substitutions in a long-term evolution experiment with E.
      coli does not support this hypothesis. In particular, the extent of synonymous
      variation across genes in that experiment does not reflect the variation observed
      in natural isolates of E. coli. Instead, gene length alone predicts with high
      accuracy the prevalence of synonymous changes in the experimental populations. We
      hypothesize that patterns of synonymous variation in natural E. coli populations
      are instead caused by differences across genomic regions in their effective
      population size that, in turn, reflect different histories of recombination,
      horizontal gene transfer, selection, and population structure. 

PMID- 26199376
TI  - Evolutionary Transition from Pathogenicity to Commensalism: Global Regulator
      Mutations Mediate Fitness Gains through Virulence Attenuation.
AB  - Symbiotic interactions are indispensable for metazoan function, but their origin
      and evolution remain elusive. We use a controlled evolution experiment to
      demonstrate the emergence of novel commensal interactions between Pseudomonas
      aeruginosa, an initially pathogenic bacterium, and a metazoan host,
      Caenorhabditis elegans. We show that commensalism evolves through loss of
      virulence, because it provides bacteria with a double fitness advantage:
      Increased within-host fitness and a larger host population to infect.
      Commensalism arises irrespective of host immune status, as the adaptive path in
      immunocompromised C. elegans knockouts does not differ from that in wild type.
      Dissection of temporal dynamics of genomic adaptation for 125 bacterial
      populations reveals highly parallel evolution of incipient commensalism across
      independent biological replicates. Adaptation is mainly achieved through frame
      shift mutations in the global regulator lasR and nonsynonymous point mutations in
      the polymerase gene rpoB that arise early in evolution. Genetic knockouts of lasR
      not only corroborate its role in virulence attenuation but also show that further
      mutations are necessary for the fully commensal phenotype. The evolutionary
      transition from pathogenicity to commensalism as we observe here is facilitated
      by mutations in global regulators such as lasR, because few genetic changes cause
      pleiotropic effects across the genome with large phenotypic effects. Finally, we
      found that nucleotide diversity increased more quickly in bacteria adapting to
      immunocompromised hosts than in those adapting to immunocompetent hosts.
      Nevertheless, the outcome of evolution was comparable across host types.
      Commensalism can thus evolve independently of host immune state solely as a side
      effect of bacterial adaptation to novel hosts. 

PMID- 26199377
TI  - Protein Kinase C (PKC)zeta Pseudosubstrate Inhibitor Peptide Promiscuously Binds
      PKC Family Isoforms and Disrupts Conventional PKC Targeting and Translocation.
AB  - PKMzeta is generated via an alternative transcriptional start site in the
      atypical protein kinase C (PKC)zeta isoform, which removes N-terminal regulatory
      elements, including the inhibitory pseudosubstrate domain, consequently rendering
      the kinase constitutively active. Persistent PKMzeta activity has been proposed
      as a molecular mechanism for the long-term maintenance of synaptic plasticity
      underlying some forms of memory. Many studies supporting a role for PKMzeta in
      synaptic plasticity and memory have relied on the PKCzeta pseudosubstrate-derived
      zeta-inhibitory peptide (ZIP). However, recent studies have demonstrated that ZIP
      induced impairments to synaptic plasticity and memory occur even in the absence
      of PKCzeta, suggesting that ZIP exerts its actions via additional cellular
      targets. In this study, we demonstrated that ZIP interacts with conventional and
      novel PKC, in addition to atypical PKC isoforms. Moreover, when brain abundance
      of each PKC isoform and affinity for ZIP are taken into account, the signaling
      capacity of ZIP-responsive pools of conventional and novel PKCs may match or
      exceed that for atypical PKCs. Pseudosubstrate-derived peptides, like ZIP, are
      thought to exert their cellular action primarily by inhibiting PKC catalytic
      activity; however, the ZIP-sensitive catalytic core of PKC is known to
      participate in the enzyme's subcellular targeting, suggesting an additional mode
      of ZIP action. Indeed, we have demonstrated that ZIP potently disrupts PKCalpha
      interaction with the PKC-targeting protein A-kinase anchoring protein (AKAP) 79
      and interferes with ionomycin-induced translocation of conventional PKC to the
      plasma membrane. Thus, ZIP exhibits broad-spectrum action toward the PKC family
      of enzymes, and this action may contribute to its unique ability to impair
      memory. 

PMID- 26199378
TI  - Invited Commentary: Fundamental Causes, Social Context, and Modifiable Risk
      Factors in the Racial/Ethnic Inequalities in Blood Pressure and Hypertension.
AB  - Racial and ethnic inequalities in blood pressure and hypertension have been well
      documented, but their causes remain unclear, making efforts to reduce these
      inequalities challenging. In this issue of the Journal, Basu et al. (Am J
      Epidemiol. 2015;182(4):345-353) address this gap in our knowledge by using an
      econometric approach to examine the role of 4 conventional risk factors for
      hypertension. Their results suggest that targeting certain risk factors will
      reduce racial inequalities in the prevalence of hypertension. However, racial
      differences in modifiable risk factors are enmeshed within disparate
      socioenvironmental contexts which are in turn determined by inequalities in the
      distribution of social, economic, and political resources and constraints. A
      small but growing body of literature suggests that targeting the intermediate
      risk factors that link racial group membership to hypertension, rather than the
      context or the inequalities in the distribution of resources and constraints,
      will ultimately result in little change in hypertension inequalities, increase
      these inequalities, or even create inequalities in poor mental health. 

PMID- 26199379
TI  - Using Decomposition Analysis to Identify Modifiable Racial Disparities in the
      Distribution of Blood Pressure in the United States.
AB  - To lower the prevalence of hypertension and racial disparities in hypertension,
      public health agencies have attempted to reduce modifiable risk factors for high
      blood pressure, such as excess sodium intake or high body mass index. In the
      present study, we used decomposition methods to identify how population-level
      reductions in key risk factors for hypertension could reshape entire population
      distributions of blood pressure and associated disparities among racial/ethnic
      groups. We compared blood pressure distributions among non-Hispanic white, non
      Hispanic black, and Mexican-American persons using data from the US National
      Health and Nutrition Examination Survey (2003-2010). When using standard adjusted
      logistic regression analysis, we found that differences in body mass index were
      the only significant explanatory correlate to racial disparities in blood
      pressure. By contrast, our decomposition approach provided more nuanced
      revelations; we found that disparities in hypertension related to tobacco use
      might be masked by differences in body mass index that significantly increase the
      disparities between black and white participants. Analysis of disparities between
      white and Mexican-American participants also reveal hidden relationships between
      tobacco use, body mass index, and blood pressure. Decomposition offers an
      approach to understand how modifying risk factors might alter population-level
      health disparities in overall outcome distributions that can be obscured by
      standard regression analyses. 

PMID- 26199380
TI  - Basu and Siddiqi Respond to "Context, Behaviors, and Hypertension Inequalities".

PMID- 26199381
TI  - Invited Commentary: A-P-C... It's Easy as 1-2-3!
AB  - Investigations of age, period, and cohort effects are difficult because the 3
      factors are linearly dependent. In a novel application, Kramer et al. (Am J
      Epidemiol. 2015;182(4):302-312) have used graphical analysis and statistical
      models to estimate the impact that age, period, and cohort effects have had on
      trends in black-white inequalities in heart disease mortality. Using a
      constrained regression approach (with the first 2 periods' effects constrained to
      zero), Kramer et al. find evidence that age and cohort effects figure more
      prominently than do period effects in contributing to relative black-white
      mortality differences, and they argue that early-life exposures should be given
      greater consideration for mitigation of racial differences in heart disease. In
      this invited commentary, I argue that the utility of age-period-cohort models for
      understanding health inequalities depends on the plausibility of the assumptions
      used to break the link between the 3 factors. Based on the existing age-period
      cohort literature, alternative assumptions seem likely to produce substantially
      different results. I also argue that interpretations of the impacts of age,
      period, and cohort effects on racial inequalities in heart disease mortality may
      depend on whether inequalities are assessed on the absolute scale or the relative
      scale. 

PMID- 26199383
TI  - Kramer and Casper Respond to "A-P-C... It's Easy as 1-2-3!".

PMID- 26199382
TI  - Decomposing Black-White Disparities in Heart Disease Mortality in the United
      States, 1973-2010: An Age-Period-Cohort Analysis.
AB  - Against the backdrop of late 20th century declines in heart disease mortality in
      the United States, race-specific rates diverged because of slower declines among
      blacks compared with whites. To characterize the temporal dynamics of emerging
      black-white racial disparities in heart disease mortality, we decomposed race-sex
      specific trends in an age-period-cohort (APC) analysis of US mortality data for
      all diseases of the heart among adults aged >=35 years from 1973 to 2010. The
      black-white gap was largest among adults aged 35-59 years (rate ratios ranged
      from 1.2 to 2.7 for men and from 2.3 to 4.0 for women) and widened with
      successive birth cohorts, particularly for men. APC model estimates suggested
      strong independent trends across generations ("cohort effects") but only modest
      period changes. Among men, cohort-specific black-white racial differences emerged
      in the 1920-1960 birth cohorts. The apparent strength of the cohort trends raises
      questions about life-course inequalities in the social and health environments
      experienced by blacks and whites which could have affected their biomedical and
      behavioral risk factors for heart disease. The APC results suggest that the
      genesis of racial disparities is neither static nor restricted to a single time
      scale such as age or period, and they support the importance of equity in life
      course exposures for reducing racial disparities in heart disease. 

PMID- 26199384
TI  - Accuracy of femoral tunnel placement in medial patellofemoral ligament
      reconstruction: the effect of a nearly true-lateral fluoroscopic view.
AB  - BACKGROUND: Reconstruction of the medial patellofemoral ligament (MPFL) is an
      established operative procedure for patients with recurrent episodes of lateral
      patellar instability. However, recent articles have reported remarkable
      complication rates, with nonanatomic femoral tunnel positioning in up to 64% of
      patients. PURPOSE: To evaluate the sensitivity of femoral tunnel placement using
      lateral fluoroscopic guidance to minor degrees of deviation from the true-lateral
      view using established radiographic landmarks. STUDY DESIGN: Controlled
      laboratory study. METHODS: Six human cadaveric femora were used for this study. A
      6-mm radiopaque eyelet was used to mark the native femoral insertion of the MPFL
      according to previously described radiographic landmarks. Radiographic landmarks
      were also applied with the femur positioned in 2.5 degrees  and 5 degrees  of
      internal and external rotation, respectively, and with the femur in 2.5 degrees 
      and 5 degrees  of hip abduction and adduction, respectively. The distance between
      the center of the 6-mm eyelet to the center of the native femoral MPFL insertion,
      as established in the true-lateral view, was measured and determined as the
      degree of shift in each position. RESULTS: Hip adduction, abduction, and internal
      and external rotations of 2.5 degrees  resulted in a shift from the native
      femoral MPFL insertion point to a more distal (adduction), proximal (abduction),
      anterior (internal rotation), and posterior location (external rotation) of 2.7
      +/- 0.7, 2.0 +/- 0.7, 2.7 +/- 1.1, and 3.0 +/- 1.3 mm, respectively (all P <
      .05). Malpositioning increased to a distance of 5.0 +/- 0.7 mm distally, 3.6 +/-
      1.0 mm proximally, 5.2 +/- 0.8 mm anteriorly, and 6.2 +/- 0.6 mm posteriorly to
      the native insertion point when the attachment was marked with 5 degrees  of
      divergence from the true-lateral view (all P < .05). CONCLUSION: The results of
      this study indicate the high sensitivity of femoral tunnel placement using
      lateral fluoroscopic guidance to minor degrees of deviation from the true-lateral
      view. CLINICAL RELEVANCE: The study highlights the importance of an exact lateral
      view when fluoroscopic guidance is used for femoral tunnel positioning in the
      daily practice of MPFL reconstruction, and a possible explanation for the high
      incidence of nonanatomic tunnel placement is suggested.

PMID- 26199385
TI  - Negative effects of heterospecific pollen receipt vary with abiotic conditions:
      ecological and evolutionary implications.
AB  - BACKGROUND AND AIMS: Studies that have evaluated the effects of heterospecific
      pollen (HP) receipt on plant reproductive success have generally overlooked the
      variability of the natural abiotic environment in which plants grow. Variability
      in abiotic conditions, such as light and water availability, has the potential to
      affect pollen-stigma interactions (i.e. conspecific pollen germination and
      performance), which will probably influence the effects of HP receipt. Thus, a
      more complete understanding of the extent, strength and consequences of plant
      plant interactions via HP transfer requires better consideration of the range of
      abiotic conditions in which these interactions occur. This study addresses this
      issue by evaluating the effects of two HP donors (Tamonea curassavica and
      Angelonia angustifolia) on the reproductive success of Cuphea gaumeri, an endemic
      species of the Yucatan Peninsula. METHODS: Mixed (conspecific pollen and HP) and
      pure (conspecific pollen only) hand-pollinations were conducted under varying
      conditions of water and light availability in a full factorial design.
      Reproductive success was measured as the number of pollen tubes that reached the
      bottom of the style. KEY RESULTS: Only one of the two HP donors had a significant
      effect on C. gaumeri reproductive success, but this effect was dependent on water
      and light availability. Specifically, HP receipt caused a decrease in pollen tube
      growth, but only when the availability of water, light or both was low, and not
      when the availability of both resources was high. CONCLUSIONS: The results show
      that the outcome of interspecific post-pollination interactions via HP transfer
      can be context-dependent and vary with abiotic conditions, thus suggesting that
      abiotic effects in natural populations may be under-estimated. Such context
      dependency could lead to spatial and temporal mosaics in the ecological and
      evolutionary consequences of post-pollination interactions.

PMID- 26199386
TI  - Serum C-Telopeptide Collagen Crosslinks and Plasma Soluble VEGFR2 as
      Pharmacodynamic Biomarkers in a Trial of Sequentially Administered Sunitinib and
      Cilengitide.
AB  - PURPOSE: Fit-for-purpose pharmacodynamic biomarkers could expedite development of
      combination antiangiogenic regimens. Plasma sVEGFR2 concentrations ([sVEGFR2])
      mark sunitinib effects on the systemic vasculature. We hypothesized that
      cilengitide would impair microvasculature recovery during sunitinib withdrawal
      and could be detected through changes in [sVEGFR2]. EXPERIMENTAL DESIGN: Advanced
      solid tumor patients received 50 mg sunitinib daily for 14 days. For the next 14
      days, patients were randomized to arm A (cilengitide 2,000 mg administered
      intravenously twice weekly) or arm B (no treatment). The primary endpoint was
      change in [sVEGFR2] between days 14 and 28. A candidate pharmacodynamic biomarker
      of cilengitide inhibition of integrin alphavbeta3, serum c-telopeptide collagen
      crosslinks (CTx), was also measured. RESULTS: Of 21 patients, 14 (7 per arm)
      received all treatments without interruption and had all blood samples available
      for analysis. The mean change and SD of [sVEGFR2] for all sunitinib-treated
      patients was consistent with previous data. There was no significant difference
      in the mean change in [sVEGFR2] from days 14 to 28 between the arms [arm A: 2.8
      ng/mL; 95% confidence interval (CI), 2.1-3.6 vs. arm B: 2.0 ng/mL; 95% CI, 0.72
      3.4; P = 0.22, 2-sample t test]. Additional analyses suggested (i) prior
      bevacizumab therapy to be associated with unusually low baseline [sVEGFR2] and
      (ii) sunitinib causes measurable changes in CTx. CONCLUSIONS: Cilengitide had no
      measurable effects on any circulating biomarkers. Sunitinib caused measurable
      declines in serum CTx. The properties of [sVEGFR2] and CTx observed in this study
      inform the design of future combination antiangiogenic therapy trials.

PMID- 26199387
TI  - Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin
      Lymphoma Outcome.
AB  - PURPOSE: There is evidence that Hodgkin Reed-Sternberg (HRS) cells in classical
      Hodgkin lymphoma (cHL) could display some molecular and morphologic markers of
      cellular senescence (CS). We hypothesized that CS mechanisms may have potential
      prognostic relevance in cHL and investigated whether the expression of the well
      established CS biomarkers p21(CIP1/WAF1) and p16(INK4a) by HRS cells might be
      predictive of the probability of event-free survival (EFS). EXPERIMENTAL DESIGN:
      The study analyzed a retrospective cohort of 147 patients and the results were
      validated on a cohort of 91 patients independently diagnosed and treated in a
      different institution. p16(INK4a) and p21(CIP1/WAF1) were categorized as
      dichotomous variables (< or >= 30% of HRS cells at diagnosis) and evaluated in
      univariate and multivariate analysis. RESULTS: Both molecules were independent
      prognostic factors. A positive staining of one of the two molecules in more than
      30% HRS cells predicted a better EFS (P < 0.01). p16(INK4a)/p21(CIP1/WAF1)
      together as a unique categorical variable (both <30%, either <30%, both >= 30%)
      sorted out three prognostic groups with better, intermediate, or worse outcome
      either overall or within I-II, bulky and advanced stages. The presence or the
      lack of the robust expression of p21(CIP1/WAF1) and/or p16(INK4a) defined the
      prognosis in our series. CONCLUSIONS: These findings point to (i) the relevance
      of CS-related mechanisms in cHL, and to (ii) the prognostic value of a simple,
      reproducible, and low-cost immunohistochemical evaluation of p16(INK4a) and
      p21(CIP1/WAF1) expression.

PMID- 26199388
TI  - Early Changes in Circulating Tumor Cells Are Associated with Response and
      Survival Following Treatment of Metastatic Neuroendocrine Neoplasms.
AB  - PURPOSE: To investigate posttreatment circulating tumor cell (CTC) counts in
      patients with neuroendocrine neoplasms (NENs) as a predictive biomarker for
      disease progression and overall survival (OS). EXPERIMENTAL DESIGN: Patients with
      metastatic NENs commencing therapy were prospectively recruited (n = 138). Blood
      samples were obtained for evaluation of CTCs using the CellSearch platform and
      for chromogranin A (CgA) at baseline, three to five (median, 4.3) weeks and 10 to
      15 (median 13.7) weeks after commencing therapy. Radiologic response and OS data
      were collected. RESULTS: There was a significant association between first
      posttreatment CTC count and progressive disease (PD; P < 0.001). Only 8% of
      patients with a favorable "CTC response" (0 CTCs at baseline and 0 at first
      posttreatment time-point; or >=50% reduction from baseline) had PD compared with
      60% in the unfavorable group (<50% reduction or increase). Changes in CTCs were
      strongly associated with OS (P < 0.001), the best prognostic group being patients
      with 0 CTCs before and after therapy; followed by those with >=50% reduction in
      CTCs [hazard ratio (HR), 3.31]; with those with a <50% reduction or increase in
      CTCs (HR, 5.07) having the worst outcome. In multivariate analysis, changes in
      CTCs had the strongest association with OS (HR, 4.13; P = 0.0002). Changes in CgA
      were not significantly associated with survival. CONCLUSIONS: Changes in CTCs are
      associated with response to treatment and OS in metastatic NENs, suggesting CTCs
      may be useful as surrogate markers to direct clinical decision making.

PMID- 26199389
TI  - Molecular Pathways: Targeting the CXCR4-CXCL12 Axis--Untapped Potential in the
      Tumor Microenvironment.
AB  - Evidence suggests that the CXC-chemokine receptor-4 pathway plays a role in
      cancer cell homing and metastasis, and thus represents a potential target for
      cancer therapy. The homeostatic microenvironment chemokine CXCL12 binds the CXCR4
      and CXCR7 receptors, activating divergent signals on multiple pathways, such as
      ERK1/2, p38, SAPK/JNK, AKT, mTOR, and the Bruton tyrosine kinase (BTK). An
      activating mutation in CXCR4 is responsible for a rare disease, WHIM syndrome
      (warts, hypogammaglobulinemia, infections, and myelokathexis), and dominant CXCR4
      mutations have also been reported in Waldenstrom macroglobulinemia. The CXCR4
      CXCL12 axis regulates the hematopoietic stem cell niche--a property that has led
      to the approval of the CXCR4 antagonist plerixafor (AMD3100) for mobilization of
      hematopoietic precursors. In preclinical models, plerixafor has shown
      antimetastatic potential in vivo, offering proof of concept. Other antagonists
      are in preclinical and clinical development. Recent evidence demonstrates that
      inhibiting CXCR4 signaling restores sensitivity to CTLA-4 and PD-1 checkpoint
      inhibitors, creating a new line for investigation. Targeting the CXCR4-CXCL12
      axis thus offers the possibility of affecting CXCR4-expressing primary tumor
      cells, modulating the immune response, or synergizing with other targeted
      anticancer therapies.

PMID- 26199390
TI  - Less Can Be More for Gene Dose and Drug Sensitivity.
AB  - CDK4 is preclinically validated as a therapeutic target in PAX3-FOXO1 fusion gene
      positive rhabdomyosarcomas. Pharmacologic targeting showed sensitivity but,
      contrary to expectation, CDK4 genomic amplification and overexpression associated
      with 25% of cases that exhibited the lowest sensitivities. This emphasizes the
      importance of tumor-specific preclinical studies to define and understand drug
      sensitivity.

PMID- 26199391
TI  - Transition between home dialysis modalities: another piece in the jigsaw of the
      integrated care pathway.

PMID- 26199393
TI  - The ESMO Guidelines Committee would like to publish the following corrections to
      manuscripts published in 2014.

PMID- 26199392
TI  - Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor
      risk relapsed or refractory germ-cell tumors.
AB  - BACKGROUND: High-dose chemotherapy (HDC) using sequential cycles of
      carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However,
      outcomes of high-risk patients in advanced relapse remain poor. We previously
      developed a new HDC regimen combining infusional gemcitabine with
      docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in
      refractory GCT. Given the high vascular endothelial growth factor expression in
      metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied
      concurrent bevacizumab and sequential HDC using GemDMC and
      ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or
      refractory disease. PATIENTS AND METHODS: Eligibility criteria included
      intermediate/high-risk relapse (Beyer Model), serum creatinine <= 1.8 mg/dl and
      adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC
      cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial
      was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from
      an expected 25% 2-year RFS in this population. RESULTS: We enrolled 43 male
      patients, median age 30 (20-49) years, with absolute refractory (N = 20),
      refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1
      5) prior relapses. Disease status right before HDC was unresponsive (N = 24,
      progressive disease 22, stable disease 2), partial response with positive markers
      (PRm(+)) (N = 8), PRm(-) (N = 7) or complete response (N = 4). Main toxicities
      were mucositis and renal. Four patients (three with baseline marginal renal
      function) died from HDC-related complications. Tumor markers normalized in 85%
      patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature
      teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median
      follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and
      58.1%, respectively. CONCLUSIONS: Sequential bevacizumab/GemDMC-bevacizumab/ICE
      shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding
      the results expected in this difficult to treat population. CLINICALTRIALSGOV:
      NCT00936936.

PMID- 26199394
TI  - Androgen receptor splice variant V7 (AR-V7) in circulating tumor cells: a coming
      of age for AR splice variants?

PMID- 26199396
TI  - Spreading spondyloarthritis: are ILCs cytokine shuttles from base camp gut?

PMID- 26199395
TI  - Mesoamerican nephropathy: geographical distribution and time trends of chronic
      kidney disease mortality between 1970 and 2012 in Costa Rica.
AB  - OBJECTIVES: Mesoamerican nephropathy is an epidemic of chronic kidney disease
      (CKD) unrelated to traditional causes, mostly observed in sugarcane workers. We
      analysed CKD mortality in Costa Rica to explore when and where the epidemic
      emerged, sex and age patterns, and relationship with altitude, climate and
      sugarcane production. METHODS: SMRs for CKD deaths (1970-2012) among population
      aged >=20 were computed for 7 provinces and 81 counties over 4 time periods. Time
      trends were assessed with age-standardised mortality rates. We qualitatively
      examined relations between mortality and data on altitude, climate and sugarcane
      production. RESULTS: During 1970-2012, age-adjusted mortality rates in the
      Guanacaste province increased among men from 4.4 to 38.5 per 100,000 vs. 3.6-8.4
      in the rest of Costa Rica, and among women from 2.3 to 10.7 per 100,000 vs. 2.6
      5.0 in the rest of Costa Rica. A significant moderate excess mortality was
      observed among men in Guanacaste already in the mid-1970s, steeply increasing
      thereafter; a similar female excess mortality appeared a decade later, remaining
      stable. Male age-specific rates were high in Guanacaste for age categories >=30,
      and since the late 1990s also for age range 20-29. The male spatiotemporal
      patterns roughly followed sugarcane expansion in hot, dry lowlands with manual
      harvesting. CONCLUSIONS: Excess CKD mortality occurs primarily in Guanacaste
      lowlands and was already present 4 decades ago. The increasing rates among
      Guanacaste men in hot, dry lowland counties with sugarcane are consistent with an
      occupational component. Stable moderate increases among women, and among men in
      counties without sugarcane, suggest coexisting environmental risk factors.

PMID- 26199397
TI  - Bortezomib in refractory ANCA-associated vasculitis: a new option?

PMID- 26199399
TI  - Historical perspective: gut dysbiosis and hypertension.

PMID- 26199398
TI  - AZT-induced mitochondrial toxicity: an epigenetic paradigm for dysregulation of
      gene expression through mitochondrial oxidative stress.
AB  - Mitochondrial dysfunction causes oxidative stress and cardiomyopathy. Oxidative
      stress also is a side effect of dideoxynucleoside antiretrovirals (NRTI) and is
      observed in NRTI-induced cardiomyopathy. We show here that treatment with the
      NRTI AZT {1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine
      2,4-dione} modulates cardiac gene expression epigenetically through production of
      mitochondrially derived reactive oxygen species. Transgenic mice with ubiquitous
      expression of mitochondrially targeted catalase (MCAT) and C57Bl/6 wild-type mice
      littermates (WT) were administered AZT (0.22 mg/day po, 35 days), and cardiac DNA
      and mRNA were isolated. In AZT-treated WT, 95 cardiac genes were differentially
      expressed compared with vehicle-treated WTs. When MCAT mice were treated with
      AZT, each of those 95 genes reverted toward the expression of vehicle-treated
      WTs. In AZT-treated WT hearts, Mthfr [5,10-methylenetetrahydrofolate reductase; a
      critical enzyme in synthesis of methionine cycle intermediates including S
      adenosylmethionine (SAM)], was overexpressed. Steady-state abundance of SAM in
      cardiac extracts from AZT-treated MCAT mice increased 60% above that of vehicle
      treated MCAT. No such change occurred in WT. AZT caused hypermethylation (47%)
      and hypomethylation (53%) of differentially methylated DNA regions in WT cardiac
      DNA. AZT-treated MCAT heart DNA exhibited greater hypermethylation (91%) and less
      hypomethylation (9%) compared with vehicle-treated MCAT controls. The gene
      encoding protein kinase C-alpha displayed multifocal epigenetic regulation caused
      by oxidative stress. Results show that mitochondrially derived oxidative stress
      in the heart hinders cardiac DNA methylation, alters steady-state abundance of
      SAM, alters cardiac gene expression, and promotes characteristic
      pathophysiological changes of cardiomyopathy. This mechanism for NRTI toxicity
      offers insight into long-term side effects from these commonly used antiviral
      agents. 

PMID- 26199400
TI  - High-fat diet caused widespread epigenomic differences on hepatic methylome in
      rat.
AB  - A high-fat (HF) diet is associated with progression of liver diseases. To
      illustrate genome-wide landscape of DNA methylation in liver of rats fed either a
      control or HF diet, two enrichment-based methods, namely methyl-DNA
      immunoprecipitation assay with high-throughput sequencing (MeDIP-seq) and
      methylation-sensitive restriction enzyme sequencing (MRE-seq), were performed in
      our study. Rats fed with the HF diet exhibited an increased body weight and liver
      fat accumulation compared with that of the control group when they were 12 wk of
      age. Genome-wide analysis of differentially methylated regions (DMRs) showed that
      12,494 DMRs induced by HF diet were hypomethylated and 6,404 were
      hypermethylated. DMRs with gene annotations [differentially methylated genes
      (DMGs)] were further analyzed to show gene-specific methylation profile. There
      were 88, 2,680, and 95 hypomethylated DMGs identified with changes in DNA
      methylation in the promoter, intragenic and downstream regions, respectively,
      compared with fewer hypermethylated DMGs (45, 1,623, and 50 in the respective
      regions). Some of these genes also contained an ACGT cis-acting motif whose DNA
      methylation status may affect gene expression. Pathway analysis showed that these
      DMGs were involved in critical hepatic signaling networks related to hepatic
      development. Therefore, HF diet had global impacts on DNA methylation profile in
      the liver of rats, leading to differential expression of genes in hepatic
      pathways that may involve in functional changes in liver development. 

PMID- 26199401
TI  - Is heterostyly rare on oceanic islands?
AB  - Heterostyly has been considered rare or absent on oceanic islands. However, there
      has been no comprehensive review on this issue. Is heterostyly truly rare on
      oceanic islands? What makes heterostyly rare on such islands? To answer these
      questions, we review the reproductive studies on heterostyly on oceanic islands,
      with special emphasis on the heterostylous genus Psychotria in the Pacific Ocean
      as a model system. Overall, not many reproductive studies have been performed on
      heterostylous species on oceanic islands. In Hawaiian Psychotria, all 11 species
      are thought to have evolved dioecy from distyly. In the West Pacific, three
      species on the oceanic Bonin and Lanyu Islands are distylous (Psychotria
      homalosperma, P. boninensis and P. cephalophora), whereas three species on the
      continental Ryukyu Islands show various breeding systems, such as distyly (P.
      serpens), dioecy (P. rubra) and monoecy (P. manillensis). On some other Pacific
      oceanic islands, possibilities of monomorphy have been reported. For many
      Psychotria species, breeding systems are unknown, although recent studies
      indicate that heterostylous species may occur on some oceanic islands. A shift
      from heterostyly to other sexual systems may occur on some oceanic islands. This
      tendency may also contribute to the rarity of heterostyly, in addition to the
      difficulty in colonization/autochthonous evolution of heterostylous species on
      oceanic islands. Further investigation of reproductive systems of Psychotria on
      oceanic islands using robust phylogenetic frameworks would provide new insights
      into plant reproduction on oceanic islands. 

PMID- 26199402
TI  - Nitrogen addition and harvest frequency rather than initial plant species
      composition determine vertical structure and light interception in grasslands.
AB  - In biodiversity experiments based on seeded experimental communities, species
      richness and species composition exert a strong influence on canopy structure and
      can lead to an improved use of aboveground resources. In this study, we want to
      explore whether these findings are applicable to agriculturally managed permanent
      grassland. Vertical layered profiles of biomass, leaf area (LA) and light
      intensity were measured in a removal-type biodiversity experiment (GrassMan) to
      compare the canopy structure in grassland vegetation of different plant species
      composition (called sward types). Additionally, the altered sward types were
      subjected to four different management regimes by a combination of the factors
      fertilization (unfertilized, NPK fertilized) and cutting frequency (one late cut
      or three cuts). In spite of large compositional differences (ratio grasses : non
      leguminous forbs : leguminous forbs ranging from 93 : 7 : 0 to 39 : 52 : 9), the
      vegetation of the same management regime hardly differed in its canopy structure,
      whereas the different management regimes led to distinct vertical profiles in the
      vegetation. However, the allocation of biomass in response to cutting and
      fertilization differed among the sward types. Vegetation dominated by grasses was
      denser and had more LA when fertilized compared with vegetation rich in dicots
      which merely grew taller. In functionally more diverse vegetation, light
      interception was not increased compared with vegetation consisting of more than
      90 % of grasses in terms of biomass. Management had a much stronger influence on
      structure and light interception than plant species composition in this grassland
      experiment. 

PMID- 26199403
TI  - Science and Culture: An ecosystem in the balance, captured in a work of art.

PMID- 26199404
TI  - Inner Workings: Finding precious metals in unlikely places.

PMID- 26199406
TI  - Are you missing leukaemia?

PMID- 26199407
TI  - The therapeutic value of atropine for critical care intubation.
AB  - Recent studies of atropine during critical care intubation (CCI) have revealed
      that neonates frequently experience bradycardia, are infrequently affected by
      ventricular arrhythmias and conduction disturbances and deaths have not been
      reported in a series of studies. The indiscriminate use of atropine is unlikely
      to alter the outcome during neonatal CCI other than reducing the frequency of
      sinus tachycardia. In contrast, older children experience a similar frequency of
      bradycardia to neonates and are more frequently affected by ventricular
      arrhythmias and conduction disturbances. Mortality during CCI is in the order of
      0.5%. Atropine has a beneficial effect on arrhythmias and conduction disturbances
      and may reduce paediatric intensive care unit mortality. The use of atropine for
      children >1 month of age may positively influence outcomes beyond a reduction in
      the frequency of sinus bradycardia. There is indirect evidence that atropine
      should be used for intubation during sepsis. Atropine should be considered when
      using suxamethonium. The reliance on heart rate as the sole measure of
      haemodynamic function during CCI is no longer justifiable. Randomised trials of
      atropine for mortality during CCI in general intensive care unit populations are
      unlikely to happen. As such, future research should be focused on establishing of
      a gold standard for haemodynamic decompensation for CCI. Cardiac output or blood
      pressure are the most likely candidates. The 'lost beat score' requires
      development but has the potential to be developed to provide an estimation of
      risk of haemodynamic decompensation from ECG data in real time during CCI. 

PMID- 26199409
TI  - LIN28: roles and regulation in development and beyond.
AB  - LIN28 is an RNA-binding protein that is best known for its roles in promoting
      pluripotency via regulation of the microRNA let-7. However, recent studies have
      uncovered new roles for LIN28 and have revealed how it functions, suggesting that
      it is more than just a regulator of miRNA biogenesis. Together, these findings
      imply a new paradigm for LIN28 - as a gatekeeper molecule that regulates the
      transition between pluripotency and committed cell lineages, in both let-7
      dependent and let-7-independent manners. Here, we provide an overview of LIN28
      function in development and disease. 

PMID- 26199408
TI  - The retromer complex in development and disease.
AB  - The retromer complex is a multimeric protein complex involved in recycling
      proteins from endosomes to the trans-Golgi network or plasma membrane. It thus
      regulates the abundance and subcellular distribution of its cargo within cells.
      Studies using model organisms show that the retromer complex is involved in
      specific developmental processes. Moreover, a number of recent studies implicate
      aberrant retromer function in photoreceptor degeneration, Alzheimer's disease and
      Parkinson's disease. Here, and in the accompanying poster, we provide an overview
      of the molecular and cellular mechanisms of retromer-mediated protein
      trafficking, highlighting key examples of retromer function in vivo. 

PMID- 26199410
TI  - The atlas of mouse development eHistology resource.
AB  - There was an error published in Development 142, 1909-1911. Author Yogmatee
      Roochun was omitted. The corrected author list appears above. The authors
      apologise to readers for this mistake.

PMID- 26199411
TI  - Computational redesign of the lipid-facing surface of the outer membrane protein
      OmpA.
AB  - Advances in computational design methods have made possible extensive engineering
      of soluble proteins, but designed beta-barrel membrane proteins await
      improvements in our understanding of the sequence determinants of folding and
      stability. A subset of the amino acid residues of membrane proteins interact with
      the cell membrane, and the design rules that govern this lipid-facing surface are
      poorly understood. We applied a residue-level depth potential for beta-barrel
      membrane proteins to the complete redesign of the lipid-facing surface of
      Escherichia coli OmpA. Initial designs failed to fold correctly, but reversion of
      a small number of mutations indicated by backcross experiments yielded designs
      with substitutions to up to 60% of the surface that did support folding and
      membrane insertion. 

PMID- 26199413
TI  - Fragile charge order in the nonsuperconducting ground state of the underdoped
      high-temperature superconductors.
AB  - The normal state in the hole underdoped copper oxide superconductors has proven
      to be a source of mystery for decades. The measurement of a small Fermi surface
      by quantum oscillations on suppression of superconductivity by high applied
      magnetic fields, together with complementary spectroscopic measurements in the
      hole underdoped copper oxide superconductors, point to a nodal electron pocket
      from charge order in YBa2Cu3(6+delta). Here, we report quantum oscillation
      measurements in the closely related stoichiometric material YBa2Cu4O8, which
      reveals similar Fermi surface properties to YBa2Cu3(6+delta), despite the
      nonobservation of charge order signatures in the same spectroscopic techniques,
      such as X-ray diffraction, that revealed signatures of charge order in
      YBa2Cu3(6+delta). Fermi surface reconstruction in YBa2Cu4O8 is suggested to occur
      from magnetic field enhancement of charge order that is rendered fragile in zero
      magnetic fields because of its potential unconventional nature and/or its
      occurrence as a subsidiary to more robust underlying electronic correlations.

PMID- 26199412
TI  - Simultaneous deletion of the methylcytosine oxidases Tet1 and Tet3 increases
      transcriptome variability in early embryogenesis.
AB  - Dioxygenases of the TET (Ten-Eleven Translocation) family produce oxidized
      methylcytosines, intermediates in DNA demethylation, as well as new epigenetic
      marks. Here we show data suggesting that TET proteins maintain the consistency of
      gene transcription. Embryos lacking Tet1 and Tet3 (Tet1/3 DKO) displayed a strong
      loss of 5-hydroxymethylcytosine (5hmC) and a concurrent increase in 5
      methylcytosine (5mC) at the eight-cell stage. Single cells from eight-cell
      embryos and individual embryonic day 3.5 blastocysts showed unexpectedly variable
      gene expression compared with controls, and this variability correlated in
      blastocysts with variably increased 5mC/5hmC in gene bodies and repetitive
      elements. Despite the variability, genes encoding regulators of cholesterol
      biosynthesis were reproducibly down-regulated in Tet1/3 DKO blastocysts,
      resulting in a characteristic phenotype of holoprosencephaly in the few embryos
      that survived to later stages. Thus, TET enzymes and DNA cytosine modifications
      could directly or indirectly modulate transcriptional noise, resulting in the
      selective susceptibility of certain intracellular pathways to regulation by TET
      proteins. 

PMID- 26199414
TI  - Near-infrared fluorescence molecular imaging of amyloid beta species and
      monitoring therapy in animal models of Alzheimer's disease.
AB  - Near-infrared fluorescence (NIRF) molecular imaging has been widely applied to
      monitoring therapy of cancer and other diseases in preclinical studies; however,
      this technology has not been applied successfully to monitoring therapy for
      Alzheimer's disease (AD). Although several NIRF probes for detecting amyloid beta
      (Abeta) species of AD have been reported, none of these probes has been used to
      monitor changes of Abetas during therapy. In this article, we demonstrated that
      CRANAD-3, a curcumin analog, is capable of detecting both soluble and insoluble
      Abeta species. In vivo imaging showed that the NIRF signal of CRANAD-3 from 4-mo
      old transgenic AD (APP/PS1) mice was 2.29-fold higher than that from age-matched
      wild-type mice, indicating that CRANAD-3 is capable of detecting early molecular
      pathology. To verify the feasibility of CRANAD-3 for monitoring therapy, we first
      used the fast Abeta-lowering drug LY2811376, a well-characterized beta-amyloid
      cleaving enzyme-1 inhibitor, to treat APP/PS1 mice. Imaging data suggested that
      CRANAD-3 could monitor the decrease in Abetas after drug treatment. To validate
      the imaging capacity of CRANAD-3 further, we used it to monitor the therapeutic
      effect of CRANAD-17, a curcumin analog for inhibition of Abeta cross-linking. The
      imaging data indicated that the fluorescence signal in the CRANAD-17-treated
      group was significantly lower than that in the control group, and the result
      correlated with ELISA analysis of brain extraction and Abeta plaque counting. It
      was the first time, to our knowledge, that NIRF was used to monitor AD therapy,
      and we believe that our imaging technology has the potential to have a high
      impact on AD drug development. 

PMID- 26199415
TI  - Memory formation and retrieval of neuronal silencing in the auditory cortex.
AB  - Sensory stimuli not only activate specific populations of cortical neurons but
      can also silence other populations. However, it remains unclear whether neuronal
      silencing per se leads to memory formation and behavioral expression. Here we
      show that mice can report optogenetic inactivation of auditory neuron ensembles
      by exhibiting fear responses or seeking a reward. Mice receiving pairings of
      footshock and silencing of a neuronal ensemble exhibited a fear response
      selectively to the subsequent silencing of the same ensemble. The valence of the
      neuronal silencing was preserved for at least 30 d and was susceptible to
      extinction training. When we silenced an ensemble in one side of auditory cortex
      for conditioning, silencing of an ensemble in another side induced no fear
      response. We also found that mice can find a reward based on the presence or
      absence of the silencing. Neuronal silencing was stored as working memory. Taken
      together, we propose that neuronal silencing without explicit activation in the
      cerebral cortex is enough to elicit a cognitive behavior. 

PMID- 26199416
TI  - Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel
      nonsteroidal therapy for endometriosis.
AB  - Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant,
      inflammatory gynecological disease of reproductive age women. Two major clinical
      symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or
      infertility, which profoundly affect the quality of life in women. Current
      hormonal therapies to induce a hypoestrogenic state are unsuccessful because of
      undesirable side effects, reproductive health concerns, and failure to prevent
      recurrence of disease. There is a fundamental need to identify nonestrogen or
      nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid
      concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis,
      and this increased PGE2 plays important role in survival and growth of
      endometriosis lesions. The objective of the present study was to determine the
      effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on
      molecular and cellular aspects of the pathogenesis of endometriosis and
      associated clinical symptoms. Using human fluorescent endometriotic cell lines
      and chimeric mouse model as preclinical testing platform, our results, to our
      knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i)
      decreases growth and survival of endometriosis lesions; (ii) decreases
      angiogenesis and innervation of endometriosis lesions; (iii) suppresses
      proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain;
      (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant
      molecular environment of the endometrium and endometriosis lesions; and (v)
      restores endometrial functional receptivity through multiple mechanisms. Our
      novel findings provide a molecular and preclinical basis to formulate long-term
      nonestrogen or nonsteroidal therapy for endometriosis. 

PMID- 26199417
TI  - Tissue fusion over nonadhering surfaces.
AB  - Tissue fusion eliminates physical voids in a tissue to form a continuous
      structure and is central to many processes in development and repair. Fusion
      events in vivo, particularly in embryonic development, often involve the purse
      string contraction of a pluricellular actomyosin cable at the free edge. However,
      in vitro, adhesion of the cells to their substrate favors a closure mechanism
      mediated by lamellipodial protrusions, which has prevented a systematic study of
      the purse-string mechanism. Here, we show that monolayers can cover well
      controlled mesoscopic nonadherent areas much larger than a cell size by purse
      string closure and that active epithelial fluctuations are required for this
      process. We have formulated a simple stochastic model that includes purse-string
      contractility, tissue fluctuations, and effective friction to qualitatively and
      quantitatively account for the dynamics of closure. Our data suggest that, in
      vivo, tissue fusion adapts to the local environment by coordinating lamellipodial
      protrusions and purse-string contractions. 

PMID- 26199418
TI  - Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses.
AB  - Infection of cells with DNA viruses triggers innate immune responses mediated by
      DNA sensors. cGMP-AMP synthase (cGAS) is a key DNA sensor that produces the
      cyclic dinucleotide cGMP-AMP (cGAMP) upon activation, which binds to and
      activates stimulator of interferon genes (STING), leading to IFN production and
      an antiviral response. Kaposi's sarcoma-associated herpesvirus (KSHV) is a DNA
      virus that is linked to several human malignancies. We report that KSHV infection
      activates the cGAS-STING pathway, and that cGAS and STING also play an important
      role in regulating KSHV reactivation from latency. We screened KSHV proteins for
      their ability to inhibit this pathway and identified six viral proteins that
      block IFN-beta activation through this pathway. This study is the first report
      identifying multiple viral proteins encoded by a human DNA virus that inhibit the
      cGAS-STING DNA sensing pathway. One such protein, viral interferon regulatory
      factor 1 (vIRF1), targets STING by preventing it from interacting with TANK
      binding kinase 1 (TBK1), thereby inhibiting STING's phosphorylation and
      concomitant activation, resulting in an inhibition of the DNA sensing pathway.
      Our data provide a unique mechanism for the negative regulation of STING-mediated
      DNA sensing. Moreover, the depletion of vIRF1 in the context of KSHV infection
      prevented efficient viral reactivation and replication, and increased the host
      IFN response to KSHV. The vIRF1-expressing cells also inhibited IFN-beta
      production following infection with DNA pathogens. Collectively, our results
      demonstrate that gammaherpesviruses encode inhibitors that block cGAS-STING
      mediated antiviral immunity, and that modulation of this pathway is important for
      viral transmission and the lifelong persistence of herpesviruses in the human
      population. 

PMID- 26199420
TI  - Antenna molecule drives solar hydrogen generation.

PMID- 26199419
TI  - A role for the mevalonate pathway in early plant symbiotic signaling.
AB  - Rhizobia and arbuscular mycorrhizal fungi produce signals that are perceived by
      host legume receptors at the plasma membrane and trigger sustained oscillations
      of the nuclear and perinuclear Ca(2+) concentration (Ca(2+) spiking), which in
      turn leads to gene expression and downstream symbiotic responses. The activation
      of Ca(2+) spiking requires the plasma membrane-localized receptor-like kinase
      Does not Make Infections 2 (DMI2) as well as the nuclear cation channel DMI1. A
      key enzyme regulating the mevalonate (MVA) pathway, 3-Hydroxy-3-Methylglutaryl
      CoA Reductase 1 (HMGR1), interacts with DMI2 and is required for the legume
      rhizobium symbiosis. Here, we show that HMGR1 is required to initiate Ca(2+)
      spiking and symbiotic gene expression in Medicago truncatula roots in response to
      rhizobial and arbuscular mycorrhizal fungal signals. Furthermore, MVA, the direct
      product of HMGR1 activity, is sufficient to induce nuclear-associated Ca(2+)
      spiking and symbiotic gene expression in both wild-type plants and dmi2 mutants,
      but interestingly not in dmi1 mutants. Finally, MVA induced Ca(2+) spiking in
      Human Embryonic Kidney 293 cells expressing DMI1. This demonstrates that the
      nuclear cation channel DMI1 is sufficient to support MVA-induced Ca(2+) spiking
      in this heterologous system. 

PMID- 26199421
TI  - Reply to Oron: Electric vehicles provide an opportunity to reduce environmental
      health effects of transportation.

PMID- 26199422
TI  - A unique serpin P1' glutamate and a conserved beta-sheet C arginine are key
      residues for activity, protease recognition and stability of serpinA12 (vaspin).
AB  - SerpinA12 (vaspin) is thought to be mainly expressed in adipose tissue and has
      multiple beneficial effects on metabolic, inflammatory and atherogenic processes
      related to obesity. KLK7 (kallikrein 7) is the only known protease target of
      vaspin to date and is inhibited with a moderate inhibition rate. In the crystal
      structure, the cleavage site (P1-P1') of the vaspin reactive centre loop is
      fairly rigid compared with the flexible residues before P2, possibly supported by
      an ionic interaction of P1' glutamate (Glu(379)) with an arginine residue
      (Arg(302)) of the beta-sheet C. A P1' glutamate seems highly unusual and
      unfavourable for the protease KLK7. We characterized vaspin mutants to
      investigate the roles of these two residues in protease inhibition and
      recognition by vaspin. Reactive centre loop mutations changing the P1' residue or
      altering the reactive centre loop conformation significantly increased inhibition
      parameters, whereas removal of the positive charge within beta-sheet C impeded
      the serpin-protease interaction. Arg(302) is a crucial contact to enable vaspin
      recognition by KLK7 and it supports moderate inhibition of the serpin despite the
      presence of the detrimental P1' Glu(379), which clearly represents a major
      limiting factor for vaspin-inhibitory activity. We also show that the vaspin
      inhibition rate for KLK7 can be modestly increased by heparin and demonstrate
      that vaspin is a heparin-binding serpin. Noteworthily, we observed vaspin as a
      remarkably thermostable serpin and found that Glu(379) and Arg(302) influence
      heat-induced polymerization. These structural and functional results reveal the
      mechanistic basis of how reactive centre loop sequence and exosite interaction in
      vaspin enable KLK7 recognition and regulate protease inhibition as well as
      stability of this adipose tissue-derived serpin. 

PMID- 26199423
TI  - Importance of Large Intestine in Regulating Bile Acids and Glucagon-Like Peptide
      1 in Germ-Free Mice.
AB  - It is known that 1) elevated serum bile acids (BAs) are associated with decreased
      body weight, 2) elevated glucagon-like peptide-1 (GLP-1) levels can decrease body
      weight, and 3) germ-free (GF) mice are resistant to diet-induced obesity. The
      purpose of this study was to test the hypothesis that a lack of intestinal
      microbiota results in more BAs in the body, resulting in increased BA-mediated
      transmembrane G protein-coupled receptor 5 (TGR5) signaling and increased serum
      GLP-1 as a mechanism of resistance of GF mice to diet-induced obesity. GF mice
      had 2- to 4-fold increased total BAs in the serum, liver, bile, and ileum. Fecal
      excretion of BAs was 63% less in GF mice. GF mice had decreased secondary BAs and
      increased taurine-conjugated BAs, as anticipated. Surprisingly, there was an
      increase in non-12alpha-OH BAs, namely, beta-muricholic acid, ursodeoxycholic
      acid (UDCA), and their taurine conjugates, in GF mice. Further, in vitro
      experiments confirmed that UDCA is a primary BA in mice. There were minimal
      changes in the mRNA of farnesoid X receptor target genes in the ileum (Fibroblast
      growth factor 15, small heterodimer protein, and ileal bile acid-binding
      protein), in the liver (small heterodimer protein, liver receptor homolog-1, and
      cytochrome P450 7a1), and BA transporters (apical sodium dependent bile acid
      transporter, organic solute transporter alpha, and organic solute transporter
      beta) in the ileum of GF mice. Surprisingly, there were marked increases in BA
      transporters in the large intestine. Increased GLP-1 levels and gallbladder size
      were observed in GF mice, suggesting activation of TGR5 signaling. In summary,
      the GF condition results in increased expression of BA transporters in the colon,
      resulting in 1) an increase in total BA concentrations in tissues, 2) a change in
      BA composition to favor an increase in non-12alpha-OH BAs, and 3) activation of
      TGR5 signaling with increased gallbladder size and GLP-1.

PMID- 26199424
TI  - Making Transporter Models for Drug-Drug Interaction Prediction Mobile.
AB  - The past decade has seen increased numbers of studies publishing ligand-based
      computational models for drug transporters. Although they generally use small
      experimental data sets, these models can provide insights into structure-activity
      relationships for the transporter. In addition, such models have helped to
      identify new compounds as substrates or inhibitors of transporters of interest.
      We recently proposed that many transporters are promiscuous and may require
      profiling of new chemical entities against multiple substrates for a specific
      transporter. Furthermore, it should be noted that virtually all of the published
      ligand-based transporter models are only accessible to those involved in creating
      them and, consequently, are rarely shared effectively. One way to surmount this
      is to make models shareable or more accessible. The development of mobile apps
      that can access such models is highlighted here. These apps can be used to
      predict ligand interactions with transporters using Bayesian algorithms. We used
      recently published transporter data sets (MATE1, MATE2K, OCT2, OCTN2, ASBT, and
      NTCP) to build preliminary models in a commercial tool and in open software that
      can deliver the model in a mobile app. In addition, several transporter data sets
      extracted from the ChEMBL database were used to illustrate how such public data
      and models can be shared. Predicting drug-drug interactions for various
      transporters using computational models is potentially within reach of anyone
      with an iPhone or iPad. Such tools could help prioritize which substrates should
      be used for in vivo drug-drug interaction testing and enable open sharing of
      models. 

PMID- 26199425
TI  - Single-Nucleotide Polymorphisms in Cytochrome P450 2E1 (CYP2E1) 3'-Untranslated
      Region Affect the Regulation of CYP2E1 by miR-570.
AB  - Human cytochrome P450 2E1 (CYP2E1) catalyzes the metabolism of numerous
      xenobiotics, including acetaminophen and ethanol. CYP2E1 expression is known to
      be extensively regulated by post-transcriptional and post-translational
      mechanisms. A previous study had reported that a single-nucleotide polymorphism
      (SNP) 1561A>G in the 3'-untranslated region (3'-UTR) of CYP2E1 leads to a
      decreased CYP2E1 mRNA level in human peripheral blood mononuclear cells. In this
      study, we examined the possibility that microRNA(s) (miR) may be involved in the
      SNP-mediated modulation of CYP2E1 expression. Genotyping and sequencing analyses
      revealed that another SNP, 1556T>A, in the 3'-UTR was in complete linkage
      disequilibrium with the SNP 1561A>G. We termed the alleles with 1556T and 1561A
      or 1556A and 1561G haplotype I or II, respectively. A luciferase assay revealed
      that miR-570 recognizes the CYP2E1 3'-UTR of haplotype I but not haplotype II.
      Human embryonic kidney 293 (HEK293) cell lines stably expressing human CYP2E1
      that included the 3'-UTR of haplotype I or II (HEK/2E1(I) or HEK/2E1(II) cells,
      respectively) were established. Overexpression of miR-570 significantly decreased
      the CYP2E1 protein level in the HEK/2E1(I) cells but not in the HEK/2E1(II)
      cells. In seven human livers with diplotype I/I, the CYP2E1 protein levels were
      inversely correlated with the miR-570 levels, but no relationship was observed in
      25 human livers with diplotypes I/II and II/II. Collectively, it was demonstrated
      that human CYP2E1 was regulated by miR-570 in a genotype-dependent manner. This
      report describes the first proof that SNP in 3'-UTR of human P450 affects binding
      of miRNA to modulate the expression in the liver.

PMID- 26199426
TI  - Role of miRNA-146 in proliferation and differentiation of mouse neural stem
      cells.
AB  - Neural stem cells (NSCs) have been defined as neural cells with the potential to
      self-renew and eventually generate all cell types of the nervous system. NSCs
      serve as an ideal cell type for nervous system repair. In the present study, miR
      146 overexpression and predicted target (notch 1) were used to study
      proliferation and differentiation of mouse NSCs. shRNA were used to demonstrate
      the function of Notch 1 in proliferation of mouse NSCs and luciferase reporter
      assay was used to assess and confirm the binding sequence of 3'-UTR between Notch
      1 and miR-146. Results showed that miR-146 overexpression and knockdown of notch
      1 inhibited proliferation of mouse NSCs under serum-free cultural conditions and
      promoted spontaneous differentiation of mouse NSCs under contained serum cultural
      conditions respectively. Mouse NSCs spontaneously underwent differentiation into
      neurogenic cells with contained serum medium. However, when miR-146 was
      overexpressed, differentiation efficiency of glial cells from NSCs was increased,
      suggesting that Notch1 promoted NSC proliferation and repressed spontaneous
      differentiation of NSC in serum-free medium. In conclusion, our results
      demonstrate that miR-146 promoted spontaneous differentiation of NSCs, and this
      mechanism was influenced by miR-146, as well as its target (notch 1) and
      downstream gene.

PMID- 26199427
TI  - 'Speaking up' about patient safety concerns and unprofessional behaviour among
      residents: validation of two scales.
AB  - OBJECTIVE: To develop and test the psychometric properties of two new survey
      scales aiming to measure the extent to which the clinical environment supports
      speaking up about (a) patient safety concerns and (b) unprofessional behaviour.
      METHOD: Residents from six large US academic medical centres completed an
      anonymous, electronic survey containing questions regarding safety culture and
      speaking up about safety and professionalism concerns. RESULTS: Confirmatory
      factor analysis supported two separate, one-factor speaking up climates (SUCs)
      among residents; one focused on patient safety concerns (SUC-Safe scale) and the
      other focused on unprofessional behaviour (SUC-Prof scale). Both scales had good
      internal consistency (Cronbach's alpha>0.70) and were unique from validated
      safety and teamwork climate measures (r<0.85 for all correlations), a measure of
      discriminant validity. The SUC-Safe and SUC-Prof scales were associated with
      participants' self-reported speaking up behaviour about safety and
      professionalism concerns (r=0.21, p<0.001 and r=0.22, p<0.001, respectively), a
      measure of concurrent validity, while teamwork and safety climate scales were
      not. CONCLUSIONS: We created and provided evidence for the reliability and
      validity of two measures (SUC-Safe and SUC-Prof scales) associated with self
      reported speaking up behaviour among residents. These two scales may fill an
      existing gap in residency and safety culture assessments by measuring the
      openness of communication about safety and professionalism concerns, two
      important aspects of safety culture that are under-represented in existing
      metrics.

PMID- 26199428
TI  - Barriers and facilitators related to the implementation of surgical safety
      checklists: a systematic review of the qualitative evidence.
AB  - OBJECTIVE: The objective of this review is to obtain a better understanding of
      the user-related barriers against, and facilitators for, the implementation of
      surgical safety checklists. METHODS: We searched MEDLINE for articles describing
      stakeholders' perspectives regarding, and experiences with, the implementation of
      surgical safety checklists. The quality of the papers was assessed by means of
      the Qualitative Assessment and Review Instrument. Thematic synthesis was used to
      integrate the emergent descriptive themes into overall analytical themes.
      RESULTS: The synthesis of 18 qualitative studies indicated that implementation
      requires change in the workflow of healthcare professionals as well as in their
      perception of the checklist and the perception of patient safety in general. The
      factors impeding or advancing the required change concentrated around the
      checklist, the implementation process and the local context. We found that the
      required safety checks disrupt operating theatre staffs' routines. Furthermore,
      conflicting priorities and different perspectives and motives of stakeholders
      complicate checklist implementation. When approaching the checklist as a simple
      technical intervention, the expectation of cooperation between surgeons,
      anaesthetists and nurses is often not addressed, reducing the checklist to a tick
      off exercise. CONCLUSIONS: The complex reality in which the checklist needs to be
      implemented requires an approach that includes more than eliminating barriers and
      supporting facilitating factors. Implementation leaders must facilitate team
      learning to foster the mutual understanding of perspectives and motivations, and
      the realignment of routines. This paper provides a pragmatic overview of the user
      related barriers and facilitators upon which theories, hypothesising potential
      change strategies and interactions, can be developed and tested empirically.

PMID- 26199429
TI  - Arrhythmias: drugs and devices.

PMID- 26199430
TI  - A brief history of the European Society of Cardiology.
AB  - A look back on the history of the European Society of Cardiology which officially
      came into existence in 1950.

PMID- 26199431
TI  - Estrogen receptor antagonism uncovers gender-dimorphic suppression of whole body
      fat oxidation in humans: differential effects of tamoxifen on the GH and gonadal
      axes.
AB  - CONTEXT: Tamoxifen, a selective estrogen receptor modulator, suppresses GH
      secretion in women but not in men. It increases testosterone levels in men. As GH
      and testosterone stimulate fat metabolism, the metabolic consequences of
      tamoxifen may be greater in women than in men. OBJECTIVE: To determine whether
      tamoxifen suppresses fat oxidation (Fox) to a greater degree in women than in
      men. DESIGN: An open-label study of ten healthy postmenopausal women and ten
      healthy men receiving 2-week treatment with tamoxifen (20  mg/day). ENDPOINT
      MEASURES: GH response to arginine stimulation, serum levels of IGF1, testosterone
      and LH (men only), sex hormone binding globulin (SHBG) and whole body basal and
      postprandial Fox. RESULTS: In women, tamoxifen significantly reduced the mean GH
      response to arginine stimulation (Delta -87%, P<0.05) and circulating IGF1 levels
      (Delta -23.5+/-5.4%, P<0.01). Tamoxifen reduced postprandial Fox in women (Delta 
      34.6+/-10.3%; P<0.05). In men, tamoxifen did not affect the GH response to
      arginine stimulation but significantly reduced mean IGF1 levels (Delta -24.8+/
      6.1%, P<0.01). Tamoxifen increased mean testosterone levels (Delta 52+/-14.2%;
      P<0.01). Fox was not significantly affected by tamoxifen in men. CONCLUSION:
      Tamoxifen attenuated the GH response to stimulation and reduced postprandial Fox
      in women but not in men. We conclude that at a therapeutic dose, the suppressive
      effect of tamoxifen on fat metabolism is gender-dependent. Higher testosterone
      levels may mitigate the suppression of GH secretion and Fox during tamoxifen
      treatment in men.

PMID- 26199432
TI  - Copper Filtration and kVp: Effect on Entrance Skin Exposure.
AB  - BACKGROUND: The selection of technical factors to produce an image is driven
      primarily by the patient, body part, and factors regarding the status of that
      patient or part. Analog receptor systems are restricted by the ranges of data
      they are able to record, as well as the quantity and quality of data required to
      record an image. Using digital receptors allows for a wider range of exposure
      factors because of the nature of the receptor systems and the data processing
      methods employed. Thus, factor selection can be more patient centered when using
      digital receptors to produce a radiograph. PURPOSE: To explore the relationship
      between milliampere seconds (mAs), kilovoltage peak (kVp), and additional copper
      filtration with exposure indicators and entrance skin exposure (ESE) using both
      analog and digital receptors. RESULTS: Researchers conducted 2-tailed t-tests
      using Stata/IC version 11.2 software (StataCorp LP) to compare ESE from several
      trials using hip and knee phantoms. The analysis indicated that increasing kVp,
      adding 0.1 mm copper filtration, and correspondingly reducing mAs reduced ESE on
      a hip phantom by 64%, from 151 mR to 54.4 mR and reduced ESE on a knee phantom by
      51%, from 27.2 mR to 13.4 mR. CONCLUSION: Radiology departments and radiologic
      technologists can consider these data when creating dose reduction protocols. The
      wider latitude range of digital radiography can be used to minimize patient
      exposure while still producing images of diagnostic quality within the acceptable
      exposure indicator range stated by the manufacturer.

PMID- 26199433
TI  - Submandibular Duct Fistula Caused by a Large Sialolith: Incidental Finding in a
      Barium Swallow Study.
AB  - BACKGROUND: This case report details an incidental finding of a submandibular
      duct fistula to a patient's posterior mouth floor found on a barium swallow
      examination that was performed to rule out gastrological causes of substernal
      chest pain. The radiologist was unable to determine the cause of the filling
      defect at the time of the study. The patient's history revealed that a large
      calculus of unknown size had been passed spontaneously through the floor of the
      mouth, rupturing the proximal gland duct and creating the fistula. DISCUSSION:
      Sialolithiasis is the formation of calculi in the salivary gland and is the most
      common disease of the salivary glands, with the submandibular glands affected
      more often than others. The condition is more common in men than in women and
      most often affects individuals aged between 30 and 60 years. CONCLUSION: In
      general, the etiology of sialolithiasis is unknown. However, examining
      comorbidities and possible risk factors, such as tobacco use, and how they alter
      the saliva and the function of the salivary glands might lead to a better
      understanding of their cause.

PMID- 26199434
TI  - DigiBit: A System for Adjusting Radiographic Exposure Factors in the Digital Era.
AB  - OBJECTIVE: To develop an exposure adaptation system for direct radiography that
      can accurately adjust exposure factors such as milliampere seconds (mAs),
      kilovoltage peak, and source-to-image distance for patients of differing size.
      METHODS: The DuPont Bit System was used to select the mAs for 60 combinations of
      exposure factors for an anthropomorphic pelvic phantom. The exposure index (EI)
      with a target value of 1500 +/- 2% was used to evaluate whether each image was
      exposed correctly. The DuPont Bit System was then adapted for direct radiography
      so the mAs could be adjusted to achieve both the target bit value and the target
      EI. RESULTS: With the DuPont Bit System, an EI of 1500 +/- 21.6% was achieved in
      all 60 radiographs, whereas the target EI of 1500 +/- 2% was achieved in 16
      radiographs. With the modified version of the DuPont Bit System, "the DigiBit
      system," achieving the target EI increased to 38 out of 60 radiographs.
      DISCUSSION: The DigiBit system is an exposure adjustment system designed for
      direct radiography. In situations where automatic exposure control is not
      available, the Digibit system allows adjustment of radiographic exposure. It is
      potentially a valuable tool for radiography. CONCLUSION: The DigiBit system
      provides an accurate method of adjusting exposure factors for direct radiography.

PMID- 26199435
TI  - Adverse Effects of Iodine-derived Intravenous Radiopaque Contrast Media.
AB  - Although the advent of nonionic low-osmolar contrast agents has reduced the
      probability of a reaction to radiopaque contrast media derived from tri-iodinated
      benzoic acid, reactions still occur. Radiologic technologists must understand and
      know how to manage adverse effects of contrast media. Prompt attention to
      patients who exhibit the early signs of an adverse reaction can help to ensure
      the reaction does not progress to become severe or life-threatening. 

PMID- 26199436
TI  - Radiofrequency Ablation for Liver Cancer.
AB  - Interventional ablative technologies aided by imaging techniques such as
      ultrasonography, computed tomography, and magnetic resonance imaging have been
      crucial in managing patients with primary liver cancer and liver metastases over
      the past 20 years. Several ablative technologies have been used to treat liver
      cancer; however, radiofrequency ablation (RFA) has emerged as the most common
      ablative therapy for hepatic lesions, both in the United States and globally. RFA
      is the treatment of choice for patients who cannot have surgical resection of the
      liver. This article focuses on the role of imaging in RFA treatment of primary
      and metastatic hepatic lesions. 

PMID- 26199440
TI  - Spontaneous Hemoperitoneum.

PMID- 26199441
TI  - Assessment: Working Backward.

PMID- 26199442
TI  - Stakeholder Engagement Essential to Health Information Technology Project
      Success.

PMID- 26199443
TI  - Enhancing Patient Care Through Communication.

PMID- 26199444
TI  - Can Critical-Thinking Skills Be Taught?

PMID- 26199445
TI  - Patents Demystified.

PMID- 26199446
TI  - Imaging Plate Saturation.

PMID- 26199447
TI  - The Art and Science of Light: An Illustrated Retrospective.

PMID- 26199448
TI  - Case Study: Neuroglial Cyst.

PMID- 26199449
TI  - Computed Tomography of Pancreatitis and Pancreatic Cancer.
AB  - Pancreatic disease often is asymptomatic until tissue damage and complications
      occur or until malignancies have reached advanced stages and have metastasized.
      Contrast-enhanced multidetector computed tomography plays a central role in
      diagnosing, staging, and treatment planning for pancreatitis and pancreatic
      cancer. This article introduces the functional anatomy of the pancreas and common
      bile duct and the epidemiology, pathobiology, and computed tomography imaging of
      pancreatitis, calculi, and pancreatic cancer. 

PMID- 26199450
TI  - Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells
      in polycystic ovary syndrome women.
AB  - Women with polycystic ovary syndrome (PCOS) undergoing IVF-embryo transfer based
      assisted reproductive technology (ART) treatment show variable ovarian responses
      to exogenous FSH administration. For better understanding and control of PCOS
      ovarian responses in ART, the present study was carried out to compare the
      follicular hormones and the expression of granulosa cell genes between PCOS and
      non-PCOS women during ART treatment as well as their IVF outcomes. Overall, 138
      PCOS and 78 non-PCOS women were recruited for the present study. Follicular fluid
      collected from PCOS women showed high levels of testosterone. The expression of
      aromatase was found significantly reduced in luteinized granulosa cells from PCOS
      women. In cultured luteinized granulosa cells isolated from non-PCOS women, their
      exposure to testosterone at a level that was observed in PCOS follicles could
      decrease both mRNA and protein levels of aromatase in vitro. The inhibitory
      effect of testosterone was abolished by androgen receptor antagonist, flutamide.
      These results suggest that the hyperandrogenic follicular environment may be a
      key hazardous factor leading to the down-regulation of aromatase in PCOS. 

PMID- 26199451
TI  - Monitoring Dead Space in Mechanically Ventilated Children: Volumetric Capnography
      Versus Time-Based Capnography.
AB  - BACKGROUND: Volumetric capnography dead-space measurements (physiologic dead
      space-to-tidal-volume ratio [VD/VT] and alveolar VD/VT) are considered more
      accurate than the more readily available time-based capnography dead-space
      measurement (end-tidal alveolar dead-space fraction [AVDSF]). We sought to
      investigate the correlation between volumetric capnography and time-based
      capnography dead-space measurements. METHODS: This was a single-center
      prospective cohort study of 65 mechanically ventilated children with arterial
      lines. Physiologic VD/VT, alveolar VD/VT, and AVDSF were calculated with each
      arterial blood gas using capnography data. RESULTS: We analyzed 534 arterial
      blood gases from 65 children (median age 4.9 y, interquartile range 1.7-12.8).
      The correlation between physiologic VD/VT and AVDSF (r = 0.66, 95% CI 0.59-0.72)
      was weaker than the correlation between alveolar VD/VT and AVDSF (r = 0.8, 95% CI
      0.76-0.85). The correlation between physiologic VD/VT and AVDSF was weaker in
      children with low PaO2 /FIO2 (< 200 mm Hg), low exhaled VT (< 100 mL), a
      pulmonary reason for mechanical ventilation, or large airway VD (> 3 mL/kg). All
      3 dead-space measurements were highly correlated (r > 0.7) in children without
      hypoxemia (PaO2 /FIO2 > 300 mm Hg), mechanically ventilated for a neurologic or
      cardiac reason, or on significant inotropes or vasopressors. CONCLUSIONS: In
      mechanically ventilated children without significant hypoxemia or with cardiac
      output-related dead-space changes, physiologic VD/VT was highly correlated with
      AVDSF and alveolar VD/VT. In children with significant hypoxemia, physiologic
      VD/VT was poorly correlated with AVDSF. Alveolar VD/VT and AVDSF correlated well
      in most tested circumstances. Therefore, AVDSF may be useful in most children for
      alveolar dead-space monitoring.

PMID- 26199452
TI  - Quality of Life and Bronchial Hyper-Responsiveness in Subjects With
      Bronchiectasis: Validation of the Seattle Obstructive Lung Disease Questionnaire
      in Bronchiectasis.
AB  - BACKGROUND: Bronchiectasis can adversely affect quality of life. However, the
      tests examining quality of life in bronchiectasis are not sufficient. We examined
      the validity of a measure designed for COPD, the Seattle Obstructive Lung Disease
      Questionnaire (SOLQ), in bronchiectasis. In addition, we aimed to compare the
      quality of life of subjects with bronchiectasis and bronchial hyper
      responsiveness with that of those without to identify the effective factors.
      METHODS: We studied 78 subjects with clinically stable bronchiectasis and 41
      healthy controls matched for age and sex. Subjects were assessed by the SOLQ. A
      detailed history, physical examination, the Medical Outcomes Study 36-Item Short
      Form questionnaire, the Hospital Anxiety and Depression Scale, and spirometric
      measurements were obtained. RESULTS: Cronbach alpha coefficients, which reflected
      internal consistency, were >0.70 for all SOLQ components except for treatment
      satisfaction. SOLQ component scores correlated with all of the component scores
      of the Medical Outcomes Study 36-Item Short Form questionnaire and the Hospital
      Anxiety and Depression Scale, confirming their concurrent validity. All SOLQ
      scores correlated positively with percent-of-predicted FEV1, whereas the physical
      function, treatment satisfaction, and emotional function correlated negatively
      with the exacerbation frequency in Pearson analysis. Emotional and physical
      functions were positively associated with percent-of-predicted FEV1 in linear
      regression analysis. Compared with subjects without bronchial hyper
      responsiveness, those with bronchial hyper-responsiveness had lower FEV1/FVC and
      more exacerbations/y. Compared with bronchiectasis subjects without bronchial
      hyper-responsiveness, those with bronchial hyper-responsiveness had significantly
      lower SOLQ, physical function, and coping skills scores but not emotional
      function and treatment satisfaction. CONCLUSIONS: The SOLQ is a valid instrument
      for determining quality of life in subjects with bronchiectasis. Subjects with
      bronchiectasis and bronchial hyper-responsiveness had a poorer quality of life,
      lower baseline spirometric values, and more frequent exacerbations, suggesting
      more severe disease.

PMID- 26199453
TI  - Final 10-year effectiveness and safety results from study DE020: adalimumab
      treatment in patients with rheumatoid arthritis and an inadequate response to
      standard therapy.
AB  - OBJECTIVE: To evaluate the long-term effectiveness and safety of 10 years of
      adalimumab (ADA) treatment in DMARD-refractory RA patients and to analyse
      efficacy based on RF status and baseline disease duration. METHODS: DE020 was a
      multicentre, phase 3, open-label continuation study. Adult RA patients who
      received s.c. ADA (40 mg every other week or monthly) in one of four early
      assessment studies could receive ADA for <=10 years in DE020. Assessments
      included the 28-joint DAS with CRP (DAS28-CRP), Simplified Disease Activity Index
      (SDAI), HAQ Disability Index (HAQ-DI) and safety as events per 100 patient-years.
      RESULTS: Of 846 enrolled patients, mean age at baseline was 55.6 years, 78.1%
      were women, mean disease duration was 11.7 years and 27.0% were RF(-). Among 286
      (33.8%) patients who completed 10 years of ADA, 168/236 (71.2%) achieved DAS28
      CRP <=3.2, 101/238 (42.4%) achieved HAQ-DI <0.5 and 90/241 (37.3%) achieved DAS28
      CRP <=3.2 plus HAQ-DI <0.5. DAS28-CRP- or SDAI-based remission was observed in
      135/236 (57.2%) and 70/236 (29.7%) patients, respectively. Effectiveness outcomes
      were similar regardless of RF status. Higher proportions of patients with shorter
      vs longer baseline disease duration (<=2 vs >2 years) achieved HAQ-DI <0.5 (60.6%
      vs 39.5%; P = 0.023) and DAS28-CRP <=3.2 plus HAQ-DI <0.5 (58.1% vs 32.5%; P =
      0.006). Adverse events (317.2 events per 100 patient-years) during ADA exposure
      were consistent with the expected safety profile for TNF inhibitors. CONCLUSION:
      ADA led to sustained clinical and functional responses in the 33.8% of treatment
      refractory RA patients who completed 10 years of treatment. Patients with shorter
      disease duration achieved better outcomes, highlighting the need for early
      treatment. No unexpected safety findings were observed. TRIAL REGISTRATION:
      ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT00195650.

PMID- 26199454
TI  - O6-Methylguanosine leads to position-dependent effects on ribosome speed and
      fidelity.
AB  - Nucleic acids are under constant assault from endogenous and environmental agents
      that alter their physical and chemical properties. O6-methylation of guanosine
      (m(6)G) is particularly notable for its high mutagenicity, pairing with T, during
      DNA replication. Yet, while m(6)G accumulates in both DNA and RNA, little is
      known about its effects on RNA. Here, we investigate the effects of m(6)G on the
      decoding process, using a reconstituted bacterial translation system. m(6)G at
      the first and third position of the codon decreases the accuracy of tRNA
      selection. The ribosome readily incorporates near-cognate aminoacyl-tRNAs (aa
      tRNAs) by forming m(6)G-uridine codon-anticodon pairs. Surprisingly, the
      introduction of m(6)G to the second position of the codon does not promote
      miscoding, but instead slows the observed rates of peptide-bond formation by
      >1000-fold for cognate aa-tRNAs without altering the rates for near-cognate aa
      tRNAs. These in vitro observations were recapitulated in eukaryotic extracts and
      HEK293 cells. Interestingly, the analogous modification N6-methyladenosine
      (m(6)A) at the second position has only a minimal effect on tRNA selection,
      suggesting that the effects on tRNA selection seen with m(6)G are due to altered
      geometry of the base pair. Given that the m6G:U base pair is predicted to be
      nearly indistinguishable from a Watson-Crick base pair, our data suggest that the
      decoding center of the ribosome is extremely sensitive to changes at the second
      position. Our data, apart from highlighting the deleterious effects that these
      adducts pose to cellular fitness, shed new insight into decoding and the process
      by which the ribosome recognizes codon-anticodon pairs. 

PMID- 26199456
TI  - THE WEIGHT OF SUCCESS: THE BODY MASS INDEX AND ECONOMIC WELL-BEING IN SOUTHERN
      AFRICA.
AB  - We show that body mass increases with economic resources among most Southern
      Africans, although not all. Among Black South Africans the relationship is non
      decreasing over virtually the entire range of incomes/wealth. Furthermore in this
      group other measures of "success" (e.g., employment and education) are also
      associated with increases in body mass. This is true in both 1998 (the
      Demographic and Health Survey) and 2008 (National Income Dynamics Survey). A
      similar relationship holds among residents of Lesotho, Swaziland, Mozambique,
      Malawi, and Namibia. This suggests that body mass can be used as a crude measure
      of well-being. This allows us to examine the vexed question in South African
      labor economics whether there is involuntary unemployment. The fact that the
      unemployed are lighter than the employed, even when we control for household
      fixed effects, suggests that they are not choosing this state.

PMID- 26199455
TI  - Differential effects of Ydj1 and Sis1 on Hsp70-mediated clearance of stress
      granules in Saccharomyces cerevisiae.
AB  - Stress granules and P-bodies are conserved assemblies of nontranslating mRNAs in
      eukaryotic cells that can be related to RNA-protein aggregates found in some
      neurodegenerative diseases. Herein, we examine how the Hsp70/Hsp40 protein
      chaperones affected the assembly and disassembly of stress granules and P-bodies
      in yeast. We observed that Hsp70 and the Ydj1 and Sis1 Hsp40 proteins accumulated
      in stress granules and defects in these proteins led to decreases in the
      disassembly and/or clearance of stress granules. We observed that individual
      Hsp40 proteins have different effects on stress granules with defects in Ydj1
      leading to accumulation of stress granules in the vacuole and limited recovery of
      translation following stress, which suggests that Ydj1 promotes disassembly of
      stress granules to promote translation. In contrast, defects in Sis1 did not
      affect recovery of translation, accumulated cytoplasmic stress granules, and
      showed reductions in the targeting of stress granules to the vacuole. This
      demonstrates a new principle whereby alternative disassembly machineries lead to
      different fates of components within stress granules, thereby providing
      additional avenues for regulation of their assembly, composition, and function.
      Moreover, a role for Hsp70 and Hsp40 proteins in stress granule disassembly
      couples the assembly of these stress responsive structures to the proteostatic
      state of the cell. 

PMID- 26199458
TI  - Higher Body Mass Index Is Associated with Subjective Olfactory Dysfunction.
AB  - BACKGROUND: Morbidly obese patients demonstrate altered olfactory acuity. There
      has been no study directly assessing Body Mass Index (BMI) in patients with
      olfactory dysfunction. Our purpose was to compare BMI in a group of patients with
      subjective olfactory dysfunction to those without subjective olfactory
      complaints. METHODS: Retrospective matched case-control study. Sixty patients who
      presented to a tertiary care otolaryngology center with subjective smell
      dysfunction over one year were identified. Neoplastic and obstructive etiologies
      were excluded. Demographics, BMI, and smoking status were reviewed. Sixty age,
      gender, and race matched control patients were selected for comparison. Chi
      square testing was used. RESULTS: 48 out of 60 patients (80%) in the olfactory
      dysfunction group fell into the overweight or obese categories, compared to 36
      out of 60 patients (60%) in the control group. There was a statistically
      significant difference between the olfactory dysfunction and control groups for
      this stratified BMI (p = 0.0168).   CONCLUSION: This study suggests high BMI is
      associated with olfactory dysfunction. Prospective clinical research should
      examine this further to determine if increasing BMI may be a risk factor in
      olfactory loss and to elucidate what role olfactory loss may play in diet and
      feeding habits of obese patients.

PMID- 26199457
TI  - Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with
      [123I]-CLINME, a New SPECT Tracer for the Translocator Protein.
AB  - The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4'-iodophenyl)-3
      (N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled
      with iodine-123 and assessed for its sensitivity for the TSPO in rodents.
      Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model
      were detected using SPECT imaging. [(123)I]-CLINME was prepared in 70-80%
      radiochemical yield. The uptake of [(123)I]-CLINME was evaluated in rats by
      biodistribution, competition, and metabolite studies. The unilateral excitotoxic
      lesion was performed by injection of alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid unilaterally into the striatum. The striatum lesion was confirmed
      and correlated with TSPO expression in astrocytes and activated microglia by
      immunohistochemistry and autoradiography. In vivo studies with [(123)I]-CLINME
      indicated a biodistribution pattern consistent with TPSO distribution and the
      competition studies with PK11195 and Ro 5-4864 showed that [(123)I]-CLINME is
      selective for this site. The metabolite study showed that the extractable
      radioactivity was unchanged [(123)I]-CLINME in organs which expresses TSPO.
      SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean
      ratio uptake in striatum (lesion:nonlesion) was 2.2. Moreover, TSPO changes
      observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry,
      and autoradiography. These results indicated that [(123)I]-CLINME is a promising
      candidate for the quantification and visualization of TPSO expression in
      activated astroglia using SPECT.

PMID- 26199459
TI  - Mental State Inferences Abilities Contribution to Verbal Irony Comprehension in
      Older Adults with Mild Cognitive Impairment.
AB  - OBJECTIVE: The present study examined mentalizing capacities as well as the
      relative implication of mentalizing in the comprehension of ironic and sincere
      assertions among 30 older adults with mild cognitive impairment (MCI) and 30
      healthy control (HC) subjects. METHOD: Subjects were administered a task
      evaluating mentalizing by means of short stories. A verbal irony comprehension
      task, in which participants had to identify ironic or sincere statements within
      short stories, was also administered; the design of the task allowed uniform
      implication of mentalizing across the conditions. RESULTS: Findings indicated
      that participants with MCI have second-order mentalizing difficulties compared to
      HC subjects. Moreover, MCI participants were impaired compared to the HC group in
      identifying ironic or sincere stories, both requiring mental inference
      capacities. CONCLUSION: This study suggests that, in individuals with MCI,
      difficulties in the comprehension of ironic and sincere assertions are closely
      related to second-order mentalizing deficits. These findings support previous
      data suggesting a strong relationship between irony comprehension and
      mentalizing.

PMID- 26199460
TI  - Dengue Virus Infection Causes the Activation of Distinct NF-kappaB Pathways for
      Inducible Nitric Oxide Synthase and TNF-alpha Expression in RAW264.7 Cells.
AB  - Infection with dengue virus (DENV) causes an increase in proinflammatory
      responses, such as nitric oxide (NO) generation and TNF-alpha expression;
      however, the molecular mechanism underlying this inflammatory activation remains
      undefined, although the activation of the transcription factor NF-kappaB is
      generally involved. In addition to TNF-alpha production in DENV-infected murine
      macrophage RAW264.7 cells, inducible NO synthase was transcriptionally and
      posttranslationally elevated and accompanied by NO generation. NF-kappaB is known
      to be activated by DENV infection. Pharmacologically inhibiting NF-kappaB
      activation abolishes iNOS/NO biosynthesis and TNF-alpha production. With
      inhibition, the potential role of NF-kappaB in oxidative signaling regulation was
      prevented during DENV infection. Heat-inactivated DENV failed to cause the
      identified inflammatory responses. Pharmacological inhibition of TLR3 partly
      decreased NF-kappaB activation; however, it effectively abolished inducible
      iNOS/NO biosynthesis but did not inhibit TNF-alpha production. In contrast to
      TLR3, viral protein NS2B3 also independently contributed to NF-kappaB activation
      to regulate TNF-alpha production. These results show the distinct pathways for NF
      kappaB activation caused by DENV infection individually for the regulation of
      iNOS/NO and TNF-alpha expression. 

PMID- 26199461
TI  - Tissue Transglutaminase-Regulated Transformed Growth Factor-beta1 in the Parasite
      Links Schistosoma japonicum Infection with Liver Fibrosis.
AB  - Transforming growth factor (TGF-beta1) is among the strongest factors of liver
      fibrogenesis, but its association with Schistosoma-caused liver fibrosis is
      controversial. Tissue transglutaminase (tTG) is the principal enzyme controlling
      TGF-beta1 maturation and contributes to Sj-infected liver fibrosis. Here we aim
      to explore the consistency between tTG and TGF-beta1 and TGF-beta1 source and its
      correlation with liver fibrosis after Sj-infection. TGF-beta1 was upregulated at
      weeks 6 and 8 upon liver fibrosis induction. During tTG inhibition, TGF-beta1
      level decreased in sera and liver of infected mice. TGF-beta1 showed positive
      staining in liver containing Sj adult worms and eggs. TGF-beta1 was also detected
      in Sj adult worm sections, soluble egg antigen and Sj adult worm antigen, and
      adult worms' culture medium. The TGF-beta1 mature peptide cDNA sequence and its
      extended sequence were amplified through RT-PCR and RACE-PCR using adult worms as
      template, and sequence is analyzed and loaded to NCBI GenBank (number
      GQ338152.1). TGF-beta1 transcript in Sj eggs was higher than in adult worms. In
      Sj-infected liver, transcriptional level of TGF-beta1 from Sj, but not mouse
      liver, correlated with liver fibrosis extent. This study provides evidence that
      tTG regulates TGF-beta1 and illustrates the importance of targeting tTG in
      treating Sj infection-induced fibrosis. 

PMID- 26199462
TI  - The Impact of Immunosenescence on Pulmonary Disease.
AB  - The global population is aging with significant gains in life expectancy
      particularly in the developed world. Consequently, greater focus on understanding
      the processes that underlie physiological aging has occurred. Key facets of
      advancing age include genomic instability, telomere shortening, epigenetic
      changes, and declines in immune function termed immunosenescence.
      Immunosenescence and its associated chronic low grade systemic "inflamm-aging"
      contribute to the development and progression of pulmonary disease in older
      individuals. These physiological processes predispose to pulmonary infection and
      confer specific and unique clinical phenotypes observed in chronic respiratory
      disease including late-onset asthma, chronic obstructive pulmonary disease, and
      pulmonary fibrosis. Emerging concepts of the gut and airway microbiome further
      complicate the interrelationship between host and microorganism particularly from
      an immunological perspective and especially so in the setting of
      immunosenescence. This review focuses on our current understanding of the aging
      process, immunosenescence, and how it can potentially impact on various pulmonary
      diseases and the human microbiome. 

PMID- 26199464
TI  - Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on
      Endothelial Glycocalyx Shedding.
AB  - The aim of this study is to determine the mechanism of sepsis-induced vascular
      hyperpermeability and the beneficial effect of glucocorticoid in protecting
      vascular endothelium. Male Sprague-Dawley rats were given either a bolus
      intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli 055:B5, 10
      mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were
      also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the
      matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS
      injection). Both activities and protein levels of MMP-2 (p < 0.001) and MMP-9 (p
      < 0.001) were significantly upregulated in aortic homogenates from LPS-treated
      rats, associated with decreased ZO-1 (p < 0.001) and syndecan-1 (p = 0.011)
      protein contents. Both dexamethasone and doxycycline could significantly inhibit
      MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition
      of MMPs by dexamethasone was significantly lower than that by doxycycline, while
      the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic
      aorta was significantly higher in the dexamethasone-treated compared to the
      doxycycline-treated (p = 0.03). In conclusion, activation of MMPs plays important
      role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial
      perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that
      may contribute to the rescue of ZO-1 and syndecan-1 expression.

PMID- 26199465
TI  - Intranasal Dexmedetomidine on Stress Hormones, Inflammatory Markers, and
      Postoperative Analgesia after Functional Endoscopic Sinus Surgery.
AB  - BACKGROUND: A strong ongoing intraoperative stress response can cause serious
      adverse reactions and affect the postoperative outcome. This study evaluated the
      effect of intranasally administered dexmedetomidine (DEX) in combination with
      local anesthesia (LA) on the relief of stress and the inflammatory response
      during functional endoscopic sinus surgery (FESS). METHODS: Sixty patients
      undergoing FESS were randomly allocated to receive either intranasal DEX (DEX
      group) or intranasal saline (Placebo group) 1 h before surgery. Stress hormones,
      inflammatory markers, postoperative pain relief, hemodynamic variables, blood
      loss, surgical field quality, body movements, and satisfaction were assessed.
      RESULTS: Plasma epinephrine, norepinephrine, and blood glucose levels were
      significantly lower in DEX group as were the plasma IL-6 and TNF-alpha levels (P
      < 0.05). The weighted areas under the curve (AUCw) of the VAS scores were also
      significantly lower in DEX group at 2-12 h after surgery (P < 0.001).
      Furthermore, hemodynamic variables, blood loss, body movements, discomfort with
      hemostatic stuffing, surgical field quality, and satisfaction scores of patients
      and surgeons were significantly better (P < 0.05) in DEX group. CONCLUSIONS:
      Patients receiving intranasal DEX with LA for FESS exhibited less perioperative
      stress and inflammatory response as well as better postoperative comfort with
      hemostatic stuffing and analgesia.

PMID- 26199463
TI  - Fibrosis Related Inflammatory Mediators: Role of the IL-10 Cytokine Family.
AB  - Importance of chronic fibroproliferative diseases (FDs) including pulmonary
      fibrosis, chronic kidney diseases, inflammatory bowel disease, and cardiovascular
      or liver fibrosis is rapidly increasing and they have become a major public
      health problem. According to some estimates about 45% of all deaths are
      attributed to FDs in the developed world. Independently of their etiology the
      common hallmark of FDs is chronic inflammation. Infiltrating immune cells,
      endothelial, epithelial, and other resident cells of the injured organ release an
      orchestra of inflammatory mediators, which stimulate the proliferation and
      excessive extracellular matrix (ECM) production of myofibroblasts, the effector
      cells of organ fibrosis. Abnormal amount of ECM disturbs the original organ
      architecture leading to the decline of function. Although our knowledge is
      rapidly expanding, we still have neither a diagnostic tool to detect nor a drug
      to specifically target fibrosis. Therefore, there is an urgent need for the more
      comprehensive understanding of the pathomechanism of fibrosis and development of
      novel diagnostic and therapeutic strategies. In the present review we provide an
      overview of the common key mediators of organ fibrosis highlighting the role of
      interleukin-10 (IL-10) cytokine family members (IL-10, IL-19, IL-20, IL-22, IL
      24, and IL-26), which recently came into focus as tissue remodeling-related
      inflammatory cytokines. 

PMID- 26199467
TI  - Basics of base in hemodialysis solution: Dialysate buffer production, delivery
      and decontamination.
AB  - Hemodialysis requires the use of high volumes of freshly prepared, clean
      dialysate to foster the removal of low molecular weight metabolites (i.e., urea)
      and to correct the electrolyte and acid-base imbalance of chronic renal failure.
      Dialysate is produced by mixing clean, AAMI grade water with both an acid and
      base concentrate. This purpose of this report is to describe production, mixing
      and delivery of the buffer component of dialysate, and to also to address the
      cost, safety and feasibility of producing online bicarbonate. As endotoxin
      contaminated dialysate has been associated with the release of key mediators in
      acute and chronic inflammatory diseases associated with long-term hemodialysis
      therapy, aspects of disinfecting a bicarbonate delivery loop are also addressed. 

PMID- 26199466
TI  - Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators
      of Allergic Inflammation.
AB  - Interleukin- (IL-) 17A, a pleiotropic mediator of inflammation and autoimmunity,
      potently stimulates bone-marrow neutrophil production. To explore IL-17A effects
      on eosinopoiesis, we cultured bone-marrow from wild-type mice, or mutants lacking
      inducible nitric oxide synthase (iNOS-/-), CD95 (lpr), IL-17RA, or IL-4, with IL
      5, alone or associated with IL-17A. Synergisms between IL-17A-activated, NO
      dependent, and NO-independent mechanisms and antagonisms between IL-17A and
      proallergic factors were further examined. While IL-17A (0.1-10 ng/mL) had no IL
      5-independent effect on eosinopoiesis, it dose-dependently suppressed IL-5
      induced eosinophil differentiation, by acting during the initial 24 hours. Its
      effectiveness was abolished by caspase inhibitor, zVAD-fmk. The effect of IL-17A
      (0.1-1 ng/mL) was sensitive to the iNOS-selective inhibitor aminoguanidine and
      undetectable in iNOS-/- bone-marrow. By contrast, a higher IL-17A concentration
      (10 ng/mL) retained significant suppressive effect in both conditions, unmasking
      a high-end iNOS-independent mechanism. Lower IL-17A concentrations synergized
      with NO donor nitroprusside. Eosinopoiesis suppression by IL-17A was (a)
      undetectable in bone-marrow lacking IL-17RA or CD95 and (b) actively prevented by
      LTD4, LTC4, IL-13, and eotaxin. Sensitivity to IL-17A was increased in bone
      marrow lacking IL-4; adding IL-4 to the cultures restored IL-5 responses to
      control levels. Therefore, effects of both IL-17A and proallergic factors are
      transduced by the iNOS-CD95 pathway in isolated bone-marrow. 

PMID- 26199468
TI  - Pregnancy in patients with chronic kidney disease: Maternal and fetal outcomes.
AB  - Chronic kidney diseases (CKD) adversely affects fetal and maternal outcomes
      during pregnancy. We retrospectively reviewed the renal, maternal and fetal
      outcomes of 51 pregnancies in women with CKD between July 2009 and January 2012.
      Of the 51 subjects (mean age 27.8 +/- 7.04), 32 had 19 had estimated glomerular
      filtration rate (eGFR) <60 ml/min. There was significantly greater decline in
      eGFR at 6 weeks (55.8 +/- 32.7 ml/min) after delivery as compared to values at
      conception (71.7 +/- 27.6 [P < 0.001]). The average decline of GFR after 6 weeks
      of delivery was faster in patients with GFR < 60 ml/min/1.73 m(2) at -18.8 ml/min
      (stage 3, n = 13, -20.2 ml/min; stage 4, n = 6, -15.8 ml/min) as compared to 
      15.1 ml/min in patients with GFR >= 60 ml/min/1.73 m(2). Three of the six
      patients (50%) in stage 4 CKD were started on dialysis as compared to none in
      earlier stages of CKD (P = 0.002). At the end of 1 year, all patients in stage 4
      were dialysis dependent, while only 2/13 in stage 3 were dialysis dependent (Odds
      ratio 59.8, 95% confidence interval 2.8-302, P = 0.001). Preeclampsia (PE) was
      seen in 17.6%. Only 2/32 (6.25%) patients with GFR >= 60 ml/min/1.73 m(2)
      developed PE while 7/19 (36.84%) patients with GFR < 60 ml/min developed PE. Of
      the 51 pregnancies, 15 ended in stillbirth and 36 delivered live births. Eleven
      (21.56%) live-born infants were delivered preterm and 7 (13.72%) weighed < 2,500
      g. The full-term normal delivery was significantly high (50%) in patients with
      GFR >= 60 ml/min/1.73 m(2) (P = 0.006) and stillbirth was significantly high -
      9/19 (47.36%) patients with GFR < 60 ml/min/1.73 m(2). To conclude, women with
      CKD stage 3 and 4 are at greater risk of decline in GFR, PE and adverse maternal
      and fetal outcomes as compared to women with earlier stages of CKD. 

PMID- 26199469
TI  - Pregnancy in chronic kidney disease.

PMID- 26199470
TI  - Spectrum of renal involvement in hematolymphoid neoplasms: Renal biopsy findings
      of 12 cases.
AB  - Spectrum of causes for renal dysfunction in patients with hematolymphoid
      malignancy (excluding plasma cell dyscrasia) is varied. A retrospective
      evaluation of "native" renal biopsies referred to our institute during the period
      from January 2010 to December 2013 revealed 12 cases. Age ranged between 7 and 69
      (median 54.5) years. All patients were males. The neoplasms included non-Hodgkin
      lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, Burkitt's
      lymphoma, intravascular lymphoma, Hodgkin lymphoma and chronic myeloid leukemia.
      Proteinuria was noted in 66% of the patients (nephrotic range in 5, subnephrotic
      range in 3). Renal insufficiency was noted in 100% patients. Malignancy-related
      kidney injury was noted in 75% of the cases. Renal histology showed lymphomatous
      infiltration (8), membranoproliferative glomerulonephritis (MPGN) (3),
      intracapillary monoclonal deposit disease (1) and intravascular lymphoma (1).
      Distribution of lymphomatous infiltration was diffuse in 50% and focal in 50%. We
      observed that renal dysfunction was predominantly a direct effect, that is,
      lymphomatous invasion. Paraneoplastic glomerulopathic changes occur in the form
      of MPGN. Proteinuria of >2 g/day correlated with glomerular disease. 

PMID- 26199471
TI  - Antioxidant vitamins status in children and young adults undergoing dialysis: A
      single center study.
AB  - Vitamin E and C are well-known antioxidant vitamins. Oxidative stress is common
      in chronic kidney diseases. We evaluated 43 dialysis subjects prospectively in a
      cross-sectional survey. Serum vitamin E concentration was checked in all
      subjects; 37 cases underwent blood sampling for measurement of serum vitamin C.
      The enrolled subjects consisted of 12 (27.9%) peritoneal dialysis (PD) and 25
      (58.1%) hemodialysis (HD) patients. Six (13.9%) patients were switched from PD to
      HD or vice versa. Serum concentration of vitamin E was normal, low and high in 9
      (20.9%), 31 (72%) and 3 (7.1%) patients, respectively. There were no significant
      differences regarding age, gender, modality and duration of dialysis, and
      characteristics of dialysis sessions, mean serum blood urea nitrogen, and albumin
      levels between vitamin E deficient cases with those with normal serum vitamin E
      concentration (P > 0.05 for all). The serum vitamin C levels were low in 5
      (13.5%) and normal in 32 (86.5%) patients. vitamin C deficiency was more
      prevalent in HD versus continuous ambulatory peritoneal dialysis patients (P =
      0.128). Mean serum vitamin C concentration was higher in patients who were
      supplemented by vitamin C compared with those who didn't receive the vitamin
      supplement (P = 0.043). Vitamin E deficiency was a prevalent finding and
      supplementary vitamin C 30-60 mg/day was sufficient to prevent deficiency.
      Regular assessments of serum vitamin E level may be needed in dialysis centers. 

PMID- 26199472
TI  - The safety and efficacy of high dose ferric carboxymaltose in patients with
      chronic kidney disease: A single center study.
AB  - Ferric carboxymaltose (FCM) is a parenteral, dextran-free iron formulation
      designed to overcome the limitations of existing intravenous (IV) iron
      preparations. We investigated the safety and efficacy of high dose administration
      of FCM in our anemic chronic kidney disease (CKD) patients. It was a prospective
      observational study from June 2011 to August 2013. FCM was administered as IV
      infusion 1000 mg in 250 ml of normal saline over 15-30 min. Efficacy was
      evaluated by comparing the Hb and/or serum iron status at the first follow-up
      visit after the infusion with that at the baseline. A total of 500 infusions were
      administered to 450 patients. All patients had a successful administration of the
      FCM. None of the patients had any serious drug-related AE. AE of mild to moderate
      severity observed or reported after the infusion were: accelerated hypertension
      (0.2%), feeling abnormal (0.6%), headache and bodyaches (0.6% each), and infusion
      site reaction (0.8%). 261 patients had a follow up Hb, which showed an increase
      of 1.7 +/- 1.5 g/dl after a period of 11 +/- 7.2 weeks (P = 0.001); 188 (72%)
      patients had a rise in Hb of >=1 g/dl. The increase in Hb was observed uniformly
      across all stages of CKD. Proportions of patients with an Hb of above 10 and 11
      g/dl increased from 30.2% to 62.8% and 16.1% to 37.9%, respectively (P = 0.001).
      Iron status evaluation done in 44 patients after a follow up period of 15.1 +/-
      11.5 weeks showed increases in Hb of 1.6 +/- 2.2 g/dl (P = 0.001), transferrin
      saturation of 9.1 +/- 16.9% (P = 0.001), and ferritin of 406 +/- 449 ng/ml (P =
      0.001). We conclude high dose administration of FCM is safe and well-tolerated.
      It was effective in the treatment of iron deficiency in nondialysis and
      peritoneal dialysis CKD patients. 

PMID- 26199473
TI  - Non-diabetic renal disease in type 2 diabetes mellitus: Study of renal - retinal
      relationship.
AB  - Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease
      worldwide. Non-diabetic renal disease (NDRD), is known to occur in diabetic
      patients. The renal and retinal relationship in type 2 diabetes mellitus (T2DM)
      with nephropathy is not uniform. This study was carried to study the histological
      spectrum of nephropathy in type 2 diabetic patients with proteinuria and its
      relationship with diabetic retinopathy (DR). Total 31 (males - 26; females - 5)
      proteinuric type 2 diabetic patients were studied. Average age of patients was
      50.7 years. Nephrotic syndrome was noted in 21 (67.7%) patients. Overall,
      isolated DN, NDRD and NDRD superimposed on DN (mixed lesion) were observed in 12
      (38.7%), 13 (41.9%) and 6 (19.4%) cases, respectively. DR was absent in 21/31
      (67.7%) cases. The spectrum of nephropathy in patients without DR included: DN in
      6 (28.57%), NDRD in 12 (57.14%) and mixed lesion in 3 (14.29%). Kidney histology
      in patients with DR (n-10) revealed DN in 6 (60%), NDRD in 1 (10%) and mixed
      lesion in 3 (30%) patients. Thus, absence of DR favors NDRD but does not exclude
      DN because isolated DN was noted in 28.57% cases in absence of DR. Similarly
      biopsy proven NDRD (pure NDRD; 10% and mixed lesion; 30%) was noted in 40% of
      cases in presence of DR. In summary, patients with T2DM had higher incidence of
      NDRD. DR is less frequent (32.3%) in type 2 diabetes and is a poor predictor of
      type of nephropathy. Hence, renal biopsy is essential for precise diagnosis of
      nephropathy in patients with T2DM. 

PMID- 26199474
TI  - A study of median nerve entrapment neuropathy at wrist in uremic patients.
AB  - Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy seen in
      uremic patients. The study was undertaken to estimate the frequency of CTS in
      uremic patients and to identify the most sensitive electrodiagnostic test. Study
      was conducted on 80 subjects of age 30-60 years. End-stage kidney disease
      patients were recruited for the clinical evaluation, motor nerve conduction
      studies (NCS), sensory NCS, F wave study and median-versus-ulnar comparison
      studies (palm-to-wrist mixed comparison study, digit 4 sensory latencies study
      and lumbrical-interossei comparison study). Among three different diagnostic
      modalities, frequency of CTS was found to be 17.5% with clinical evaluation, 15%
      with routine NCS studies and 25% with median-versus-ulnar comparison studies.
      Among the median-versus-ulnar comparison studies, lumbrical-interossei comparison
      study was found to be most sensitive (90%). The comparative tests for CTS are
      more sensitive compared to routine NCS and clinical examination. Among the
      comparative tests, lumbrical-interossei comparison study is the most sensitive.
      Early diagnosis of CTS may help patients of uremia to seek proper treatment at an
      appropriate time. 

PMID- 26199475
TI  - Hemorrhage from lumbar artery following percutaneous renal biopsy.
AB  - We present a 58-year-old lady who underwent ultrasound-guided renal biopsy for
      suspected acute glomerulonephritis. Within minutes, the radiologist noticed an
      echogenic band around left kidney and in the muscular planes. Computerized
      tomography revealed focal active contrast extravasation from arcuate or
      interlobular artery in lower pole of left kidney and lumbar artery at third
      lumbar vertebra. The bleeding vessel was occluded with gelfoam. 

PMID- 26199476
TI  - Daily postdilutional hemodiafiltration with FX800 polysulfone dialyzers for
      removing kappa light chains in multiple myeloma-induced kidney injury.
AB  - Multiple myeloma is an increasing cause of renal failure in the elderly. Early
      diagnosis of myeloma-associated acute renal failure is paramount and rapid
      initiation of disease-specific treatments with a combination of chemotherapy and
      dialytic therapies for instant removal of free light chains have been proposed.
      For immediate light chain removal, high cut-off dialyzers have been reported to
      yield superior light chain clearance parameters, but these dialyzers are not
      widely used due to increased treatment costs. In addition, the clinical virtue of
      hemodiafiltration (HDF) has not yet been definitively determined. We hereby
      present the case of a 70-year-old female patient with kappa light chain myeloma
      and acute on chronic renal failure. Daily HDF for 1-week using standard
      polysulfone high-flux dialyzers was implemented and led to remarkable and
      effective light chain reduction ratios between 87% and 95%. 

PMID- 26199477
TI  - Endovascular embolization of pseudoaneurysm of left colic artery developing after
      renal biopsy.
AB  - Vascular complications after percutaneous renal biopsy are uncommon and may
      require interventional management. In most of these cases, the pathology is a
      renal arterial pseudoaneurysm (PsA) or an arterio-venous fistula. Injury to other
      vessels like aorta, lumbar arteries or mesenteric arteries is rare with only one
      case of left colic artery PsA reported in literature. We report a case of a 60
      year-old female, who developed left colic artery PsA after renal biopsy, which
      was successfully embolized through endovascular route using microcoils. 

PMID- 26199478
TI  - A case of acquired Gitelman syndrome presenting as hypokalemic paralysis.
AB  - We report a case of a young female patient who presented with weakness of upper
      and lower limbs. On evaluation, she had hypokalemia, hypomagnesemia, metabolic
      alkalosis and hypocalciuria. Anti-Ro (SSA) antibody was positive. She had an
      acquired Gitelman syndrome due to primary Sjogren's syndrome (SS). SS presenting
      with features of Gitelman syndrome is very rare. 

PMID- 26199479
TI  - Grave's disease associated with immunoglobulin A nephropathy: A rare association.
AB  - Immunoglobulin A (Ig A) nephropathy is the most common form of primary
      glomerulonephritis. The association of Ig A nephropathy with Grave's disease has
      not been reported so far. We report a case of 20-year-old female with Grave's
      disease who presented with edema, facial puffiness, and decreased urine output.
      She was found to be hypertensive with renal failure and nephrotic range
      proteinuria. Renal biopsy revealed features of Ig A nephropathy. The patient was
      treated with oral corticosteroids (1 mg/kg/day). To our knowledge, this is the
      first case showing association of Grave's disease with Ig A nephropathy. 

PMID- 26199480
TI  - Spontaneous retroperitoneal hemorrhage presenting as hemoperitoneum secondary to
      renal cyst rupture in a peritoneal dialysis patient with acquired cystic kidney
      disease.
AB  - Spontaneous retroperitoneal hemorrhage (SRH) is a rare and potentially fatal
      condition. Acquired cystic kidney disease (ACKD) may cause SRH in hemodialysis
      patients. However, presentation of retroperitoneal hematoma as hemoperitoneum in
      peritoneal dialysis (PD) patients is exceedingly rare. We report a 44-year-old
      male PD patient who presented with hemoperitoneum secondary to retroperitoneal
      hematoma. The reason of SRH was rupture of the cysts of ACKD. The patient
      underwent unilateral nephrectomy with subsequent disappearance of hemoperitoneum.
      The importance of this case lies in the fact that the patients who have been
      receiving dialysis for a long time should be under surveillance in terms of ACKD
      development and potential associated complications such as cyst hemorrhage and
      malignancy. 

PMID- 26199481
TI  - Bilateral xanthogranulomatous pyelonephritis: Morphologically rotund,
      functionally lame!

PMID- 26199482
TI  - Giant renal angiomyolipomas in a patient with tuberous sclerosis.

PMID- 26199483
TI  - Duloxetine induced hyponatremia.

PMID- 26199484
TI  - Post exposure prophylaxis to occupational injuries for general dentist.
AB  - Occupational injuries which expose health-care professionals to blood-borne
      pathogens continue to be an important public health concern. Especially, dentists
      are at increased risk of exposure to Hepatitis B, Hepatitis C, and HIV. Dentists
      should remember and apply many precautions to prevent the broad spectrum of
      sharps and splash injuries that could occur during the delivery of dental care.
      This article updates and consolidates recommendations for the management of
      dental health-care personnel who have occupational exposure to blood and other
      body fluids. 

PMID- 26199485
TI  - A Review on Denture Marking Systems: A Mark in Forensic Dentistry.
AB  - "Identification through forensic science is an art of giving the corpse a name A
      real life detective work that would put even Sherlock Homes to shame." Forensic
      dentistry deals with proper handling and examination of dental evidence and
      proper evaluation and presentation of dental findings in interest of justice. The
      Prosthodontists are playing a very important role in forensic dentistry as they
      are concerned with fabrication of various prosthesis which can serve as an
      important tool for identification. Identification is essential requirement of any
      medico-legal investigation because a wrong identity may pose a problem in
      delivering justice. This article describes the different methods for
      identification/marking of the complete dentures, removable partial dentures and
      fixed partial dentures and the importance of denture marking in forensic
      investigatory purposes. The PubMed, Ebsco and Google search engines were used to
      gather the articles. 

PMID- 26199486
TI  - Current Concepts in Restoring Acquired Cranial Defects.
AB  - Restoring acquired cranial defects has been in vogue for long, and the
      reconstructive techniques continue to evolve. Over the decades various techniques
      and materials are employed in rehabilitating cranial defects. Advances in
      bioengineering, custom templates and Rapid prototyping technology has given
      greater impetus in restoring larger cranial defects. With the variety of options
      available it will be very crucial in deciding the best possible technique and
      material to rehabilitate patients with cranial defects. 

PMID- 26199487
TI  - Perceptions of Private Dental Practitioners of Specialist Prosthodontic Dental
      Services in Gujarat: A Survey.
AB  - To identify the perceptions towards and utilization of specialist Prosthodontic
      services among Private Dental Practitioners (PDPs) of Gujarat state. To study the
      influence of presence or absence of a Prosthodontic post graduate course during
      the PDP's dental education and years of experience in practice on the decisions
      to treat Prosthodontic cases themselves or to utilise Prosthodontic speciality
      services. A postal questionnaire examined by a panel of Prosthodontists, piloted
      on 15 PDPs, was sent to 150 randomly selected private dental practitioners of
      Gujarat state. The collected data were subjected to descriptive and Chi-square
      statistical analysis. Though 78.64 % dentists considered the treatment provided
      by the Prosthodontist to be effective, only 34.95 % of them availed their
      services. 33 % PDPs without a Prosthodontic post graduate course in their
      institute were significantly more likely to refer patients to a Prosthodontist.
      Years of experience had no influence on utilization of Prosthodontic speciality
      service. 18.44 % PDPs had a Prosthodontic speciality clinic in their region,
      65.04 % did not have, whereas 11.65 % were not aware of such clinic. PDPs have
      high regards for the Prosthodontic speciality but their reported demand was less
      as compared to other specialities indicating a need for the Prosthodonitst to put
      in efforts to make the PDPs aware of their services. 

PMID- 26199488
TI  - Effectiveness of Chemical and Microwave Disinfection on Denture Biofilm Fungi and
      the Influence of Disinfection on Denture Base Adaptation.
AB  - The aims of this study were to evaluate the effectiveness of six disinfection
      methods and the influence of these methods on the adaptation of maxillary
      dentures. Acrylic resin specimens contaminated with fungi were exposed to the
      following disinfection treatments: 1. microwave oven (900 W) at full power for 5
      min (with soaking the specimen in 250 ml water), 2. microwave oven at medium
      power for 5 min (with soaking the specimen in 250 ml water), 3. sodium
      hypochlorite 5.25 % for 5 min, 4. diluted sodium hypochlorite 1:420 for 5 h, 5.
      Chlorhexidine gluconate for 5 h, 6. effervescent tablets for 15 min, 7. soaking
      in 250 ml tap water for 15 min. Colony forming units (CFUs) of remaining cells
      were counted and compared with t test (p <= 0.05). Dimensional stability was
      evaluated using aluminum die simulating the maxillary edentulous arch. Posterior
      palatal gaps were measured. Data were analyzed using one-way ANOVA test and t
      test (p <= 0.05). Microwave irradiation (at full or medium power) and sodium
      hypochlorite 5.25 % for 5 min were able to reduce the CFUs of fungi by more than
      4 log10 whereas diluted sodium hypochlorite, chlorhexidine gluconate, and
      effervescent tablets did not achieve a reduction of >2.8, 2.68 and 1.66,
      respectively. For dimensional stability test, t test revealed significant
      difference between control group and the microwave at full power group (p =
      0.000). Within the limits of this study, microwave oven at medium power and
      sodium hypochlorite (5.25 %) are effective and safe methods of disinfecting
      removable dentures. 

PMID- 26199489
TI  - Effect of Resin Cement Mixing Method on the Retention Strength of a CAD/CAM
      Zirconia Crowns.
AB  - Several treatments have been suggested to improve the retention of zirconia-based
      restorations luted with different cements. Resin cements are believed to improve
      crown retention under certain circumstances. The aim of the present study was to
      examine the effect of three cements with different mixing methods on the
      retention of CAD/CAM zirconia crowns. Thirty extracted human molars were randomly
      divided into three groups and prepared for all-ceramic crowns (6 degrees  taper,
      4-mm height and a 1.2 mm rounded shoulder finish line). A zirconia crown (Tizian
      CAD/CAM) was fabricated for each tooth. The crowns were air-abraded using
      airborne particles, adjusted, and cemented to the corresponding tooth with one of
      the following cements: Panavia F2 (PAN group), RelyX Unicem (UNH group) or RelyX
      Unicem Aplicap (UNA group). After 3,000 rounds of thermal cycling, retention was
      measured using a specific retentive jig and a universal testing machine. The
      retention strength was measured by dividing the retention force by the surface
      area of each tooth. The means of the pull-out test results for each group were
      compared using analysis of variance and Tukey's HSD test (alpha = 0.05). The mode
      of failure was examined using a stereomicroscope. The mean retention value was
      6.45 (0.34) MPa for the UNA group, 4.99 MPa (0.47) for the UNH group, and 4.45
      (0.39) for the PAN group; the differences among the three test groups were
      significant. A mixed failure was observed in 83.3 % of specimens, while no
      cohesive failure occurred in the crowns. Within the limitations of the present
      study, of the three tested cements, Relyx Unicem Aplicap cement was associated
      with the highest retention force for Tizian zirconia crowns. 

PMID- 26199490
TI  - Comparison of Marginal Gap and Microleakage in Copy-Milled and Cad-Milled
      Zirconia Copings Bonded Using Light Cure and Chemical Cure Resin Bonding Systems.
AB  - This in vitro study assessed the marginal gap and marginal microleakage in
      zirconia copings fabricated using two computer aided techniques- CAD milling and
      Copy milling and cemented to respective tooth preparations using two resin
      bonding systems, light cure and self-cure resin bonding systems. 32 extracted
      premolars were prepared to receive zirconia copings fabricated using CAD/CAM and
      Copy milling techniques. Once the copings were fabricated, the samples were
      evaluated for marginal fit prior to cementation through microscopic observation.
      Evaluation of marginal gap was done again after cementation, in order to
      incorporate the influence of the resin bonding system on the marginal microgap.
      The specimens were evaluated under the stereomicroscope for micro-leakage using
      commercial software. A comparative statistical analysis was done following data
      collection using Mann-Whitney U test, Wilcoxon test and chi-square test. The data
      collected regarding marginal gap was well within 120 u, which is in accordance
      with previous studies. However, Copy milled specimens showed statistically lesser
      marginal gap when compared to CAD milled specimens. While comparing microleakage,
      it was observed that the microleakage in Copy milled specimens bonded with light
      cure resin bonded cement was statistically lesser than that of specimens cemented
      with chemical cure resin cement.(P = 0.003). This in vitro study concluded that
      Copy milling technique fabricated zirconia restorations with lesser marginal gap
      and microleakage score in comparison to CAD milled samples. Light cure resin
      bonding system also proved to be more effective option compared to self cure
      resin bonding systems. However, the limitations of this study should be taken
      into concern and further research should be aimed at a larger sample size to
      validate the results. 

PMID- 26199491
TI  - Effect of Ceramic Thickness and Luting Agent Shade on the Color Masking Ability
      of Laminate Veneers.
AB  - The main objective of the study was to recognize the effect of ceramic thickness
      and luting agent on the extent to which the restoration masks color variations
      that may be present in the underlying dental structure. Two pressable ceramics
      were used: Lithium disilicate reinforced (IPS e.max- Ivoclar Vivadent) and
      Leucite reinforced (Cergo- Dentsply). Fifteen ceramic discs were manufactured
      from each ceramic and divided into three groups, according to the thickness (0.5,
      1, 1.5 mm). To simulate the color of a dark underlying dental structure,
      background discs, color C3, with 20 mm diameter, were made using resin composite.
      The ceramic discs with varying thicknesses were seated on the dark background of
      the resin composite with either resinous opaque cement or resinous cement. The
      color parameters were determined by the CIE Lab system of colors using a
      spectrophotometer and color differences (DeltaE) were calculated. The results
      were then statistically analyzed, using ANOVA test and Tukey HSD test. The DeltaE
      values of both ceramic systems were affected by both the luting agent and the
      ceramic thickness (P < 0.05). The use of an opaque luting agent resulted in an
      increase of the DeltaE* values for all ceramics tested, regardless of the
      thickness. For the 1.5-mm thick veneers, higher values in the color parameters
      were obtained for both ceramic materials. The color masking ability of ceramics
      used for laminate veneers is significantly affected by the thickness of the
      ceramic and the shade of the luting agent used. 

PMID- 26199492
TI  - Postural Assessment of Students Evaluating the Need of Ergonomic Seat and
      Magnification in Dentistry.
AB  - Dental students using conventional chairs need immediate change in their posture.
      Implementing an ergonomic posture is necessary as they are at high risk for
      developing musculoskeletal disorders. This study recommends the use of an
      ergonomic seat and magnification system to enhance the visibility and the posture
      of an operator. The aim of this study is to make a foray into the hazards caused
      by inappropriate posture of dental students while working. It also aims at
      creating a cognizance about the related health implications among the dental
      fraternity at large, and to understand the significance of adopting an ergonomic
      posture since the beginning of the professional course. In the present study,
      postures have been assessed by using rapid upper limb assessment (RULA). This
      method uses diagrams of body postures and three scoring tables to evaluate ones
      exposure to risk factors. Ninety students from II BDS (preclinical students in
      the second year of dental school) were assessed in three groups using three
      different seats with and without magnification system. The results recorded
      significantly higher RULA scores for the conventional seats without using the
      magnification system compared to the SSC (Salli Saddle Chair-an ergonomic seat)
      with the use of magnification system. A poor ergonomic posture can make the
      dental students get habituated to the wrong working style which might lead to
      MSDs (Musculoskeletal diseases). It is advisable to acclimatize to good habits at
      the inception of the course, to prevent MSDs later in life. 

PMID- 26199493
TI  - A Comparative Evaluation of Dimensional Accuracy and Surface Detail Reproduction
      of Four Hydrophilic Vinyl Polysiloxane Impression Materials Tested Under Dry,
      Moist, and Wet Conditions-An In Vitro Study.
AB  - Vinyl polysiloxane (VPS) impression materials have application in a wide variety
      of situations in both fixed and removable prosthodontics. A major limitation of
      VPS impression materials is their hydrophobicity. There are two aspects of this
      problem, the wettability of the polymerized impression by dental gypsum materials
      and the ability of the unpolymerized material to wet intraoral tissues. To
      address this problem, manufacturers have added surfactants and labelled these new
      products as "hydrophilic vinyl polysiloxane." The purpose of this study was to
      evaluate and compare dimensional accuracy and surface detail reproduction of four
      hydrophilic VPS impression materials, when used under dry, moist, and wet
      conditions. A total of 180 samples were made of stainless steel die similar to as
      described in ADA sp. no. 19. The die was scored with three horizontal and two
      vertical lines. Impressions were made under dry, moist and wet conditions.
      Dimensional accuracy was measured by comparing the length of the middle
      horizontal line in each impression to the same line on the metal die, by using
      Universal Length Measuring machine. A 2-way ANOVA was performed on the percentage
      change data for measured lengths of the 4 impression materials under the 3
      conditions to evaluate dimensional accuracy. Surface detail was evaluated in two
      ways: (1) by use of criteria similar to ADA sp. no. 19 for detail reproduction,
      and (2) by use of a method that categorized the impressions as satisfactory or
      unsatisfactory based on their surface characteristics: presence of pits, voids,
      or roughness. Pearson X2 (alpha = 0.05) was used to compare surface detail
      reproduction results. Conditions (dry, moist, and wet) did not cause significant
      adverse effects on the dimensional accuracy of all the four material. With both
      surface detail analyses, dry, moist, and wet conditions had a significant effect
      on the detail reproduction of all the four materials (P < 0.05). The study
      concluded that the dimensional accuracy of all the four impression materials
      tested was well within ADA standards. Best surface detail results were obtained
      only under dry conditions for all the four materials. 

PMID- 26199494
TI  - Effect of Varying Layers of Two Die Spacers on Precementation Space of Full
      Coverage Restorations.
AB  - The purpose of this study was to evaluate and compare the effect of varying
      layers of two commercially available die spacers on pre-cementation space of full
      coverage restorations in vitro and in vivo. Seven dies were prepared for each of
      15 subjects. On three dies 1, 2, 3 layers of Pico-fit and on other three dies 1,
      2, 3 layers of Yeti die spacers applied, wax pattern fabricated, invested and
      cast. Metal copings seated in vitro on die without die spacer and on prepared
      tooth of respective subject with fit-checker. Thickness of fit checker was
      measured using micrometer at mid-axial, mid-occlusal and near finish line
      locations that provided pre-cementation space. Result of ANOVA tests suggested
      significant difference among groups with varying layers. There was no significant
      difference between pre-cementation space achieved with Pico-fit and Yeti die
      spacers. The r values suggested positive correlation between the respective pair
      of in vivo and in vitro groups. (1) There was significant difference between pre
      cementation space at mid-axial and mid-occlusal sites achieved with 1, 2 and 3
      layers of die spacers except between 1 and 2 layers and 1 and 3 layers at mid
      occlusal site. (2) Pre-cementation space achieved with Pico-fit and Yeti die
      spacers did not differ significantly for same location, layers and in vitro and
      in vivo. (3) Pre-cementation space achieved in vitro was analogous to pre
      cementation space achieved in vivo for respective location, layers and die
      spacer. 

PMID- 26199495
TI  - A Comparative Study to Evaluate the Compression Resistance of Different
      Interocclusal Recording Materials: An In Vitro Study.
AB  - Recording and transferring of accurate existing occlusal records is of prime
      importance for a successful restoration. An ideal occlusal registration material
      should provide minimal resistance to mandibular closure during the registration
      of maxillomandibular relationships. Interocclusal bite registration materials are
      partly responsible for accurate precision and occlusal quality of final
      prosthetic restorations when used for mounting casts on the articulators. The aim
      of selecting this study is to compare different types of recent interocclusal
      recording materials and to find the best among them which can resist a constant
      compressive load and will give the least inaccuracies. In the present study
      compressive resistance of four interocclusal recording materials viz. Imprint
      bite, Vitual refill, Jet bite and Ramitec at various thickness (2, 5, 10 and 20
      mm) when subjected to a constant compressive load of 25 N was studied. The
      thickness of the interocclusal recoding materials were selected to simulate
      various clinical situations. For standardization, the specimens were stored at
      room temperature for 24 h to simulate the time between clinical and laboratory
      phases, N = 20 specimens from each group was selected (making a total sample size
      of N = 80). The SPSS version 17 has been used, two way ANOVA was applied to
      compare different types of recent interocclusal recording materials, p value
      <=0.05 was considered statistically significant. A total of 80 samples were
      fabricated. Results of two-way analysis of variance (p <= 0.05) indicated that
      there was a significant difference in compressive resistance among the materials
      of each thickness. The 2 mm thickness specimens showed the least compression and
      20 mm thickness specimen showed maximum compression under a constant load of 25 N
      for all the four materials tested. Virtual Refill bite registration material
      showed the least compression value than Imprint bite polyvinylsiloxane
      registration material, Ramitec polyether bite registration material and Jet bite
      polyvinylsiloxane registration material with negligible error of 0.04 mm found in
      2 mm thickness. The results of foregoing study showed that Virtual refill having
      greater resistance to compression than other interocclusal recording material at
      various thickness. It exhibit minimal distortion during compression and give
      clinician the opportunity to make only minimal adjustments to the restorations
      that were delivered from the laboratory and avoid unnecessary use of chairtime,
      or repetition of some clinical and technical stages. 

PMID- 26199496
TI  - An In Vitro Study on Effect of Ceramic Thickness and Multiple Firings on Colour
      of Metal Ceramic Restorations.
AB  - Preparation of porcelain restorations that match the natural dentition has been a
      subject of great concern for many years. An understanding of the process by which
      the colour and translucency of fixed restorations are planned and obtained so as
      to replicate the colour of its adjacent teeth is important for achieving an
      esthetic restoration. This study was done to study the effect of fabrication
      procedures such as ceramic thickness and number of firing cycles on the colour of
      metal ceramic restorations. Metal ceramic samples with three different ceramic
      thicknesses; 0.5, 1 and 1.5 mm (N = 30, n = 10 per group) were fabricated. A3
      shade of [VMK 95, VITA Zahnfabrik, Bad Sackingen, Germany] ceramic was used for
      the fabrication of samples. Samples were subject to multiple firing cycles and
      colour was measured after 2nd, 3rd, 4th, 6th, 8th and 10th firing cycle. Colour
      measurement was done objectively using spectrolino (Gretag Macbeth Inc., Germany)
      spectrophotometer. 'Repeated measures ANOVA' test was used for doing statistical
      analysis. No significant change was noticed in any of the four colour parameters
      between the baseline reading after second firing uptil the tenth firing for any
      of the three groups with different ceramic thicknesses. There was a consistent
      rise in L* or lightness of colour as the thickness of ceramic increased. Between
      group I and group III there was a consistent shift of a* axis towards the blue
      green side and there was a consistent shift in b* axis towards purple-blue with
      an increase in ceramic thickness. It was observed that there was a change in
      DeltaE with a change in ceramic thickness. There was a change of about two units
      between group I and group II and a change of about one unit between group II and
      group III. Change in DeltaE between group I and group III was the most
      significant, being about three units. It was concluded from the study that
      multiple firing cycles during fabrication of metal ceramic restorations do not
      have any effect on colour while colour varies with change in ceramic thickness. 

PMID- 26199497
TI  - Evaluation of Effect of Astringent on Oral Mucosa as a Non-surgical Preprosthetic
      Treatment Modality in Edentulous Patients: An In Vivo Study.
AB  - Preprosthetic treatments are advocated in edentulous patients to enhance the
      denture bearing areas for good denture support. Most of the times the
      preprosthetic treatments are considered only in a surgical way. Ideally every
      edentulous patient undergoing complete denture treatment needs a non-surgical
      preprosthetic treatment. So that, the denture bearing area will be properly
      prepared before the denture construction. The present study was conducted on
      thirty completely edentulous male patients who had visited to our Institute for
      the treatment. Each patient was asked to massage with astringent gel on the
      denture bearing mucosa over a 4 weeks period. Exfoliative cytology was used to
      collect the surface cells from the palatal mucosa. First scrape was taken before
      the stimulation treatment was started. The second and third scrape was taken
      after the stimulation treatment with astringent gel for each patient. In this way
      total 90 scrapes were made and the each smear was stained with the Papanicolaou's
      technique to examine under light microscope. About 100 cells were counted from
      each stained smear. The number of parabasal cells, intermediate cells and
      superficial cells were recorded to calculate the degree of keratinization.
      Statistical analysis was performed. A significant difference (p < 0.001) in
      keratinization levels was found. The mean percentage of superficial cells before
      the stimulation treatment was 79.80 %; this percentage was gradually increased to
      84.60 and 90.57 % after the 2  and 4 weeks period of stimulation treatment
      respectively with astringent gel. 

PMID- 26199498
TI  - Effect of Dietary Simulating Solvents on the Mechanical Properties of Provisional
      Restorative Materials-An In Vitro Study.
AB  - The purpose of this investigation was to evaluate the mechanical properties of
      provisional restorative materials after storage in dietary simulating solvents. A
      total of 120 specimens, 40 specimens each of Luxatemp Star, Revotek LC and DPI
      Self Cure were prepared. The specimens were divided into four groups with 10
      specimens each and stored in dietary simulating solvents for 7 days at 37 
      degrees C as follows: Group I-Control, Group II-Artificial saliva, Group III-0.02
      N Citric acid and Group IV-Heptane. After 7 days, flexural strength was obtained
      using universal testing machine at a crosshead speed of 5 mm/min and the
      fractured specimens were immediately subjected to the microhardness test knoop
      hardness number by using Knoop microhardness tester (10 gm/15 s). The data were
      analyzed for difference by use of Kruskal-Wallis and Dunn's multiple comparison
      tests using a significance level of 0.05 to determine the mean differences.
      Significant effect was observed on the properties of provisional restorative
      materials after storage in dietary simulating solvents as compared to the control
      group (p <= 0.05). Bis-acryl resin based Luxatemp Star showed significantly
      superior flexural strength and hardness as compared to the Revotek LC and DPI
      Self Cure in dietary simulating solvents. Within the limitations of this study,
      it may be concluded that dietary simulating solvents showed significant influence
      on the mechanical properties of the provisional restorative materials. 

PMID- 26199499
TI  - A Simplified Method to Fabricate a Pneumatic Ocular Prosthesis for Large Ocular
      Defects.
AB  - When an enucleation or exenteration procedure removes the entire orbital contents
      but not the eyelids, an abnormally large orbital socket is created that would
      require an equally sized volume enhancing, flush fitting ocular prosthesis. The
      solid acrylic prosthesis would rest on or in the lower fornix and owing to its
      weight, causes distortion of the lower eyelid and/or asymmetrical alignment of
      the entire palpebral fissure. The aim of this article was to describe a method of
      fabricating a pneumatic light weight custom ocular prosthesis using lost wax
      technique to overcome the deteriorating effects of conventional solid ocular
      prosthesis. 

PMID- 26199500
TI  - Effect of Preparation Taper, Height and Marginal Design Under Varying Occlusal
      Loading Conditions on Cement Lute Stress: A Three Dimensional Finite Element
      Analysis.
AB  - To assess the effect of preparation taper, height and margin design under
      different loading conditions on cement lute stress. A 3-D FE model of an upper
      second premolar and molar was developed from CT scan of human skull using
      software programmes (MIMICS, Hypermesh and ANSYS). 10 degrees  and 30 degrees 
      taper, 3 and 5 mm preparation height and shoulder and chamfer finish lines were
      used. Type 1 Glass ionomer cement with 24 MUm lute width was taken and the model
      was loaded under 100 N horizontal point load, vertical point load distributed
      axial load. The maximum shear stress and Von Mises stress within the cement lute
      were recorded. The maximum shear stresses ranged from 1.70 to 3.93 MPa
      (horizontal point loading), 0.66 to 3.04 MPa (vertical point loading), 0.38 to
      0.87 MPa (distributed loading). The maximum Von Mises stresses ranged from 3.39
      to 10.62 MPa (horizontal point loading), 1.93 to 8.58 MPa (vertical point
      loading) and 1.49 to 3.57 MPa (distributed loading). The combination of 10
      degrees  taper and 5 mm height had the lowest stress field while the combination
      of 30 degrees  taper and 5 mm height had the highest stress field. Distributed
      axial loading shows least stress, better stress homogenization and gives a
      favorable prognosis for the fixed prostheses. Smaller preparation taper of 10
      degrees  is biomechanically more acceptable than a 30 degrees  taper. It is
      desirable to decrease taper as height increases. The chamfer margin design is
      associated with greater local cement stresses toward the margins that could place
      the cement at greater risk for microfracture and failure. 

PMID- 26199501
TI  - A Comparative Evaluation of the Effect of Double Casting Technique Using
      Functionally Generated Path and Conventional Single Casting with Respect to
      Functional Articulation, Patient Satisfaction and Chair Side Time, in Single Unit
      Molar Teeth: An In Vivo Study.
AB  - A stable centric occlusal position that shows no evidence of occlusal disease
      should not be altered. Confirmative restorative dentistry deals with making
      restorations that are in harmony with existing jaw relations. Conventional
      techniques for construction have been unsuccessful in producing a prosthesis that
      can be inserted without minor intraoral occlusal adjustment. This study was
      conducted to evaluate the benefits of the double casting technique with FGP over
      the conventional casting technique. Ten patients with root canal treated
      maxillary molar were selected for the fabrication of metal crown. Two techniques,
      one involving the conventional fabrication and other using functionally generated
      path with double casting were used to fabricate the prosthesis. A comparison
      based on various parameters which was done between the two techniques. The change
      in the height of castings for the double casting group was less compared to the
      conventional group and was highly statistically significant (P < 0.001). The time
      taken for occlusal correction was significantly lower in double casting group
      than the conventional group (P < 0.001). The patient satisfaction (before
      occlusal correction) indicated better satisfaction for double casting group
      compared to conventional (P < 0.01). The functionally generated path with double
      casting technique resulted in castings which had better dimensional accuracy,
      less occlusal correction and better patient satisfaction compared to the
      conventional castings. 

PMID- 26199502
TI  - Two Body Wear of Newly Introduced Nanocomposite Teeth and Cross Linked Four
      Layered Acrylic Teeth: a Comparitive In Vitro Study.
AB  - STATEMENT OF PROBLEM: Wear of complete denture teeth results in compromise in
      denture esthetics and functions. To counteract this problem, artificial teeth
      with increased wear resistance had been introduced in the market such as
      nanocomposite teeth. PURPOSE: The purpose of this study was to compare the amount
      of wear between nanocomposite teeth and acrylic teeth. MATERIALS AND METHODS:
      Fifteen specimens were chosen from each group namely the nanocomposite teeth (SR_
      PHONARES) and the acrylic teeth (ACRY PLUS). Maxillary premolar was only chosen
      for testing and the samples were customized according to the specifications of
      the pin on disc machine. Pin on disc machine is a two body tribometer which
      quantifies the amount of wear under a specific load and time. Test samples were
      mounted on to the receptacle of the pin on disc machine and tested under a load
      of 0.3 kg for 1,000 cycles of rotation against a 600 grit emery paper. The amount
      of wear is displayed from the digital reading obtained from the pin on disc
      machine. RESULTS: After statistical analysis, it was found that, the amount of
      wear is more in four layered acrylic teeth. The p value obtained is 0.002
      (<0.005) thus implies that the difference in wear between nanocomposite teeth and
      acrylic teeth is statistically significant. CONCLUSION: Though the nanocomposite
      teeth has less amount of wear than the four layered acrylic teeth, the difference
      is very less and adds only to a little clinical significance but the cost of the
      nanocomposite is four times that of the acrylic teeth. Further clinical studies
      must be performed to confirm our results.

PMID- 26199503
TI  - Analysis of Relative Parallelism Between Hamular-Incisive-Papilla Plane and
      Campers Plane in Edentulous Subjects: A Comparative Study.
AB  - The study was undertaken to evaluate the parallelism between hamular-incisive
      papilla plane (HIP) and the Campers plane. And to determine which part of the
      posterior reference of the tragus i.e., the superior, middle or the inferior of
      the Camper's plane is parallel to HIP using digital lateral cephalograms. Fifty
      edentulous subjects with well formed ridges were selected for the study. The
      master casts were obtained using the standard selective pressure impression
      procedure. On the deepest point of the hamular notches and the centre of the
      incisive papilla stainless steel spherical bearings were glued to the cast at the
      marked points. The study templates were fabricated with autopolymerizing acrylic
      resin. The subjects were prepared for the lateral cephalograms. Stainless steel
      spherical bearings were adhered to the superior, middle, inferior points of the
      tragus of the ear and inferior border of the ala of the nose using surgical
      adhesive tape. The subjects with study templates were subjected to lateral
      cephalograms. Cephalometric tracings were done using Autocad 2010 software. Lines
      were drawn connecting the incisive papilla and hamular notch and the stainless
      steel spherical bearings placed on the superior, middle and inferior points on
      the tragus and the ala of the nose i.e., the Campers line S, Campers line M,
      Campers line I. The angles between the three Camper's line and the HIP were
      measured and recorded. Higher mean angulation was recorded in Campers line S -HIP
      (8.03) followed by Campers line M-HIP (4.60). Campers line I-HIP recorded the
      least angulation (3.80). The HIP is parallel to the Camper's plane. The Camper's
      plane formed with the posterior reference point as inferior point of the tragus
      is relatively parallel to the HIP. 

PMID- 26199504
TI  - Instructional Design for Assessment of Dental Esthetic Treatment Needs in a
      Indian Undergraduate School: A Randomised Controlled Trial.
AB  - In the recent years esthetic dentistry has been the area of focus amongst the
      public. Esthetics is an important dimension in dental practice and the upcoming
      dentists need to be enabled to demonstrate their competencies for an efficient
      clinical outcome. The purpose of this study was to institute a cultural change
      within traditional didactic dental education towards student centred learning to
      cope up with the accelerating pace of medical technological change and achieving
      positive impact on patient care and patient satisfaction. Intervention that was
      considered for the project included David Merrill's first principles of
      instruction. A randomized controlled trial was conducted with all the students
      from four cohorts of final year dental undergraduate students, divided into an
      intervention group (n = 40) and a control group (n = 40). A professional
      assessment questionnaire is used to evaluate the relationship between the
      students and professional's assessment of esthetic treatment needs. The results
      of the study indicated that the ranking of the most and least noticeable dental
      features differed significantly (p = 0.0061) between the intervention and non
      intervention group and the indicates the intervention group to be in better
      agreement with professional assessment than the non intervention group of
      students with z value of 2.7435. The relative agreement between intervention
      group of undergraduate students and the professional assessment of esthetic
      treatment need shows the importance of intervention of Merrill's first principles
      of instruction in learning, emphasising the significance of PBL and therefore
      indicating a positive impact on successful esthetic treatment for patients. 

PMID- 26199506
TI  - Electro-Mechanical Finger Prosthesis: A Novel Approach for Rehabilitation of
      Finger Amputees.
AB  - Prosthesis refers to artificial replacement of an absent part of the human body.
      These prostheses help in psychological support of the patients and enhance their
      social acceptance. Complete or partial finger amputations are some of most
      frequently encountered forms of partial hand loss. Micro vascular reconstruction
      is the first choice of rehabilitation but when it is contraindicated,
      unavailable, unsuccessful or unaffordable, the prosthetic rehabilitation is an
      alternative for improving the psychological status of an individual. Most of
      these artificial prostheses make use of silicone. The present paper tries to
      combine aesthetics with function. The authors have created functionally active
      finger prosthesis with the help of electromechanical controls. The prosthesis is
      battery-powered, light-weight, and allows the user to regain complete control of
      flexion and extension movements of an artificial finger. 

PMID- 26199505
TI  - Effect of Anatase Titanium Dioxide Nanoparticles on the Flexural Strength of Heat
      Cured Poly Methyl Methacrylate Resins: An In-Vitro Study.
AB  - Poly methyl methacrylate (PMMA) resin is the most widely used material for
      fabrication of dentures since 1937 as it exhibits adequate physical, mechanical
      and esthetic properties. But one of the major problems faced using this material
      is that, it is highly prone to plaque accumulation due to surface porosities and
      its food retentive properties. This in turn increases the bacterial activity
      causing denture stomatitis. In efforts to impart antimicrobial property to these
      resins, various nanoparticles (NP) have been incorporated viz. Silver, Zirconia
      oxide, Titanium dioxide (TiO2), Silica dioxide (SiO2) etc. However, as additives
      they can affect the mechanical properties of the final product. Therefore, the
      aim of the present study was to evaluate and compare the effect of different
      concentration of TiO2 NP on the flexural strength of PMMA resins. Specimens made
      from heat polymerizing resin (DPI) without NP were used as a control group (Group
      A). The two experimental groups, (Group B and Group C) had 0.5 and 1 %
      concentration of TiO2 NP respectively. The specimens were stored in 37  degrees C
      distilled water for 50 +/- 2 h. A three-point bending test for flexural strength
      measurement was conducted following ADA specification no. 12. The maximum mean
      flexural strength (90.65 MPa) belonged to the control group; and acrylic resin
      with 1 % TiO2 NP demonstrated the minimum mean flexural strength (76.38 MPa).
      But, the values of all the three groups exceeded the ADA Specification level of
      65 MPa. Conclusion may be drawn from the present study that addition of TiO2 NP
      into acrylic resin can adversely affect the flexural strength of the final
      product and is directly proportional to the concentration of NP. 

PMID- 26199507
TI  - Effect of Aging on Bond Strength of Two Soft Lining Materials to a Denture Base
      Polymer.
AB  - The purpose of this study was evaluation the effect of immersion in distilled
      water and inorganic artificial saliva on the shear bond strength of a heat
      polymerized and an auto-polymerized silicone-based denture lining materials. The
      denture liners investigated were Molloplast-B (heat-polymerized), and Mollosil
      plus (auto-polymerized). The soft liner specimens were 10 * 10 * 2.5 mm and were
      processed between two poly(methylmethacrylate) plates. Thirty shear specimens for
      each type of test lining material were prepared. Specimens were divided equally
      into three groups for each test lining material: first group, specimens were
      tested after 48 h of preparation without immersion; second group, specimens were
      tested following immersion in distilled water at 37  degrees C for 12 months; and
      third group, specimens were tested following immersion in inorganic artificial
      saliva at 37  degrees C for 12 months. Shear bond strength was measured using an
      universal testing machine at a crosshead speed of 40 mm/min and failure mode
      (adhesive, cohesive and mixed) after debonding was assessed. Data were
      statistically analyzed with one-way analysis of variance (ANOVA) (alpha = 0.05).
      ANOVA was followed by Bonferroni post hoc tests for pairwise comparisons. A
      significant difference in shear bond strength was detected between Molloplast-B
      and Mollosil plus following immersion in distilled water and artificial saliva.
      Molloplast-B demonstrated considerably higher shear strength than Mollosil plus
      after immersion. Shear strengths of the lining materials investigated reduced
      significantly after immersion in both solutions. Visual examination after
      separation revealed that the soft materials tested exhibited mostly adhesive
      failure. The effect of immersion in distilled water and inorganic artificial
      saliva on bond strength of test lining materials was perceivable; however, both
      of them had acceptable bond strength and might be proper for long-term use. 

PMID- 26199508
TI  - Stress Distribution Around Single Short Dental Implants: A Finite Element Study.
AB  - Bone height restrictions are more common in the posterior regions of the
      mandible, because of either bone resorption resulting from tooth loss or even
      anatomic limitations, such as the position of the inferior alveolar nerve. In
      situations where adequate bone height is not available in the posterior mandible
      region, smaller lengths of implants may have to be used but it has been reported
      that the use of long implants (length >=10 mm) is a positive factor in
      osseointegration and authors have reported failures with short implants. Hence
      knowledge about the stress generated on the bone with different lengths of
      implants needs scientific evaluation. The purpose of this study was to compare
      and evaluate the influence of different lengths of implants on stress upon bone
      in mandibular posterior area. A 3 D finite element model was made of the
      posterior mandible using the details from a CT scan, using computer software
      (ANSYS 12). Four simulated implants with lengths 6 mm, 8 mm, 10 mm and 13 mm were
      placed in the centre of the bone. A static vertical force of 250 N and a static
      horizontal force of 100 N were applied. The stress generated in the cortical and
      cancellous bone around the implant were recorded and evaluated with the help of
      ANSYS. In this study, Von Mises stress on a 6 mm implant under a static vertical
      load of 250 N appeared to be almost in the same range of 8 and 10 mm implant
      which were more as compared to 13 mm implant. Von Mises stress on a 6mm implant
      under a static horizontal load of 100 N appeared to be less when compared to 8,
      10 and 13 mm implants. From the results obtained it may be inferred that under
      static horizontal loading conditions, shorter implants receive lesser load and
      thus may tend to transfer more stresses to the surrounding bone. While under
      static vertical loading the shorter implants bear more loads and comparatively
      transmit lesser load to the surrounding bone. 

PMID- 26199509
TI  - Changing Smiles Through Multidisciplinary Approach with Predictable Aesthetics: A
      Case Report.
AB  - This clinical report describes a multidisciplinary approach for the
      rehabilitation of a young patient with mobile and missing front teeth. The
      objectives of the treatment were to eliminate tooth mobility and replacing
      missing tooth, while enhancing aesthetics and restoring masticatory function.
      Treatment included placement of endodontic stabilizer and rehabilitating missing
      tooth with fixed partial denture and gingival porcelain to satisfy the patient's
      aesthetic and functional expectations. 

PMID- 26199510
TI  - Prosthetic Correction of Postenucleation Socket Syndrome: A Case Report.
AB  - Postenucleation socket syndrome is a frequent late complication of enucleation of
      eye globe. Several pathophysiological mechanisms have been proposed to account
      for the symptoms of postenucleation socket syndrome, which include lost orbital
      volume, superior sulcus deformity, upper eyelid ptosis, lower eyelid laxity, and
      backward tilt of the prosthesis. The goal of postenucleation socket syndrome
      treatment is to achieve the best possible functional and esthetic result. The
      treatment can be either conservative or surgical. For the patient interested in a
      non-surgical correction, the conservative treatment is simple and non invasive
      and can be done with prosthesis modification for good positioning, comfort, and
      mobility. This paper describes prosthetic correction of a patient with
      postenucleation socket syndrome by modified ocular prosthesis. 

PMID- 26199511
TI  - A Viable Treatment Alternative in Distal Extension Cases: A Case Report.
AB  - Dentures requiring support from teeth, the mucosa and the underlying alveolar
      ridges are subjected to many forces that adversely effect the abutment teeth and
      the residual ridges during functional and parafunctional activity. A number of
      designs of the framework and the direct retainers were used to improve the
      comfort and acceptance of the patient wearing a removable partial denture.
      Attachment retained removable partial denture is one of the viable treatment
      alternative through which significant number of patients could be benefited. In
      this particular case of distal extension, attachment retained removable partial
      denture was chosen as a treatment modality. This article provides an overview and
      a simplified approach to this treatment through a case report and the criteria
      followed for selection of the particular attachments for treating the patient. 

PMID- 26199512
TI  - Prosthetic Rehabilitation of a Congenital Soft Palate Defect.
AB  - Obturator is derived from the Latin verb obturate which means to close or to shut
      off. This definition provides an appropriate description of the objective of
      obturation in patients with palatal defects. The obturator is often helpful in
      improving the speech of individuals with partial or total velar defects i.e.
      cleft of soft palate. Soft palate cleft is one of the most common cause of
      velopharyngeal incompetence, which is the functional inability of the soft palate
      to effectively seal with the posterior and or lateral pharyngeal walls. In
      maxillofacial prosthesis the clinician may have the responsibility for
      reestablishing palatopharyngeal integrity to provide the potential for acceptable
      speech. Here a case report has been presented in which palatal plate with a solid
      one piece pharyngeal obturator prosthesis has been used for rehabilitation of a
      dentulous patient having congenital soft palate defect using functional
      impression technique. 

PMID- 26199513
TI  - Putty Index: An Important Aid for the Direct Fabrication of Fiber Reinforced
      Composite Resin FPD.
AB  - Fiber reinforced composite resin fixed partial dentures (FRCFPD) with composite
      resin, PFM or all ceramic pontic can be used as a short term or long term
      alternative to conventional fixed partial dentures or implant supported crown in
      young patients where conventional FPD is contraindicated (large pulp chambers) or
      in patient's unwilling to invasive implant placement surgical procedure and those
      who do not want to allow preparation of natural sound abutments for placement of
      retainers for FPD. FRCFPD can be successfully used for replacing missing anterior
      tooth (Turker and Sener, J Prosthet Dent 100:254-258, 2008), in conditions which
      allows minimum occlusal loading of pontic, over jet and overbite not greater than
      3 mm (Ricketts, Provocations and perceptions in craniofacial orthopedics: dental
      science and facial art/parts 1 and 2. Rocky Mountain Orthodontics, Denver, p
      7023, 1990) and structurally sound and intact abutments for the fiber reinforced
      matrix (Rose et al., Quintessence Int 33:579-583, 2002). The successful esthetic
      and functional rehabilitation of missing tooth with fiber reinforced composite
      resin FPD depends on accurate positioning of pontic in patient's mouth. It is
      difficult to hold the pontic in proper position with instrument or fingers while
      direct fabrication in mouth. For accurate positioning, stabilization of pontic is
      very important which can be achieved with putty index. Putty index maintain
      pontic in accurate mesiodistal, labiolingual and cervicoincisal position while
      fabricating FRCFPD directly. 

PMID- 26199514
TI  - Replacement of a Congenitally Missing Maxillary Incisor by Implant Supported
      Prosthesis.
AB  - Maxillary central incisors have the least incidence of congenital absence. When
      it does happen, the patient may present with over retained deciduous centrals or
      the contralateral central may have drifted into the available space presenting as
      generalised anterior spacing with loss of midline. In such cases a multi
      disciplinary approach may be required with orthodontic treatment to re-organise
      the space available in order to rehabilitate the patient with a fixed prosthesis.
      This case report presents the treatment of a patient with congenitally missing
      maxillary left central incisor using dental implant with angulated abutment after
      orthodontic correction and stabilization of the remaining maxillary anteriors. 

PMID- 26199515
TI  - Prosthetic Rehabilitation of Partial Ear Defect: 2 Case Reports.
AB  - The loss or absence of an auricle may result from trauma, disease or congenital
      anomalies and causes a considerable aesthetic problem. If the deformity involves
      the external auditory canal, it can affect hearing. This case report describes
      the surgical and prosthetic treatment of two patients with partial defects of
      their right external ears from different causes. Implant-retained auricular
      prostheses fabricated from heat-temperature-vulcanised silicone were used in both
      the cases; they were designed to be harmonious with the remaining tissues. The
      patients experienced improved retention, aesthetics, hearing and quality of life
      with these prostheses. During the approximately 3 year follow-up, both the
      prostheses were re-fabricated once; however, problems related to implant
      stability and peri-implant tissue health were not encountered. 

PMID- 26199516
TI  - Prosthodontic Management of Unfavourably Positioned Implants.
AB  - The success rate of implant therapy has improved up to 90-95 %. This can be
      attributed to a numerous factors namely proper case selection, improved
      diagnostic and radiographic techniques, good softwares for treatment planning,
      improved surgical equipments, good surgical techniques and sophisticated implant
      design. The cost of advanced diagnostic techniques and treatment planning
      software can sometime limit them from being used routinely. In such unfortunate
      situations, older technique of exposing the ridge and placing implants wherever
      possible without regard for favorable implant position or angulation is still
      being followed. This case report describes prosthetic rehabilitation of a
      partially edentulous patient who was abandoned by a general practitioner after
      implant placement. Five implants had been placed in the maxilla in prosthetically
      unfavorable positions and angulations. Castable abutments were then used and a
      single bar was cast. This bar was then incorporated in a FP3 type of a fixed
      maxillary prosthesis opposing existing fixed partial denture in the lower jaw. 1
      year follow up shows stable implants, healthy peri-implant tissue, minimal
      probing depth and no radiographic evidence of pathology. 

PMID- 26199517
TI  - Treatment Using Functionally Fixed Prosthesis: A Case Report.
AB  - Most dental practitioners as well as their patients prefer to have fixed rather
      than removable prosthesis. However, there are many clinical situations that
      prohibit the use of the fixed treatment modality. These clinical cases can vary
      from, simply not having the proper number of healthy teeth and/or implants to,
      the esthetically challenging cases of high smile lines and severe loss of
      alveolar support. The approach of using a traditional removable prosthesis in
      these situations has always been met with severe compromises. The functionally
      fixed restoration is a third modality of treatment that can solve many of the
      problems of the removable restoration and at the same time provide the same
      comfort and success of the fixed prosthesis. This restoration has a pontic
      assembly that is removed by the patient for periodontal maintenance. This article
      presents a case report which describes a technique for treatment of partially
      edentulous maxilla with severe loss of alveolar support using a fixed removable
      prosthesis/Andrew's bridge. 

PMID- 26199518
TI  - Functional and Aesthetic Full Mouth Rehabilitation of a Severely Worn Dentition
      to Restore Vertical Dimension: A Case Report.
AB  - Deterioration or malfunction of any part should be viewed as an effect that has
      the direct or indirect result of one or more identifiable cause. The
      establishment of definitive goals is the foundation for the full mouth
      rehabilitation. Severe wear is common in prosthodontic patients whose teeth have
      been held in functional interference for long period of time. This case report
      presents a description of a patient's oral rehabilitation with metal ceramic
      restorations to increase vertical dimension while achieving canine guided
      occlusion. 

PMID- 26199520
TI  - Comprehensive Rehabilitation of Partially Amputated Index Finger with Silicone
      Prosthesis: A Case Report with 3 years of Follow Up.
AB  - The loss of all or part of a finger following traumatic amputation may have a
      negative impact on physical and psychological well-being. An esthetic prosthesis
      can offer psychological, functional, and rehabilitative advantages. One of the
      major problems associated with somato-prosthetic replacement of partially
      amputated finger is inadequate retention of the prosthesis. This may stem from
      the weight of the prosthesis, inadequate tissue support, and/or the particular
      area of the finger to be replaced. A number of means have been employed to
      enhance retention. Among the more common are adhesives, adhesive tape, magnets
      and implants. The purpose of this article is to describe a technique which
      eliminates the need for adhesive materials and utilizes copper wire to fabricate
      a finger ring as a primary means of retention. This technique can be utilized
      whenever the prosthesis encompasses more than 180 degrees  of the affected area.
      This clinical report presents a case of rehabilitation of a partially amputated
      index finger defect and describes a method of retention for the same with a
      copper ring. 

PMID- 26199519
TI  - Restorative Management of Intrinsic and Extrinsic Dental Erosion.
AB  - The restorative management of tooth surface loss is highlighted through the
      presentation of two advanced cases of dental erosion. On presentation, the causes
      of the dental erosion in both patients had been previously diagnosed and stopped.
      The first patient was a 67 year old with intrinsic erosion and an element of
      attrition where a multidisciplinary approach was used. The other, a 17 year old
      patient with extrinsic erosion managed via adhesive restorations. Adhesive
      techniques are a relatively simple, effective and conservative method for the
      treatment of dental erosion. The two treatment modalities (conventional versus
      contemporary) are compared and discussed. 

PMID- 26199521
TI  - Full Mouth Rehabilitation by Minimally Invasive Cosmetic Dentistry Coupled with
      Computer Guided Occlusal Analysis: A Case Report.
AB  - Evidence of dentistry dates back to 7000 B.C. and since then has come, indeed a
      long sophisticated way in treatment management of our dental patients. There have
      been admirable advances in the field of prosthodontics by the way of techniques
      and materials; enabling production of artificial teeth that feel, function and
      appear nothing but natural. The following case report describes the management of
      maxillary edentulousness with removable complete denture and mandibular attrition
      and missing teeth with onlays and FPD by the concept of minimally invasive
      cosmetic dentistry. Computer guided occlusal analysis was used to guide
      sequential occlusal adjustments to obtain measurable bilateral occlusal contacts
      simultaneously. 

PMID- 26199522
TI  - Strategic Use of Telescopic Retainers and Semi-rigid Precision Attachments in a
      Geriatric Patient: A Case Report.
AB  - The rehabilitation of medically compromised elderly patients with long span
      partially edentulous arches has been a tremendous challenge for dentists. Proper
      dental management requires a commitment to provide the best treatment despite the
      compromised oral conditions. The aim of this paper is to describe the prosthetic
      rehabilitation of an elderly patient who presented with chief complaints of
      gagging sensation while using upper denture, loose upper and lower dentures and
      difficulty in eating food. Patient was rehabilitated using removable partial
      denture with semi-rigid attachments in the maxillary arch and telescopic
      prosthesis in the mandibular arch. Use of semi precision attachments helped in
      increasing the retentive ability of the maxillary prosthesis, even in the
      presence of only few abutments. Fabrication of a telescopic denture is a
      technique sensitive procedure but it offers advantages like bilateral splinting
      effect in long span partially edentulous arches, reduced effective crown-root
      ratio, maintenance of proprioception and transfer of forces along the long axis
      of the abutments. Although the management was complex but it improved patient's
      esthetics, oral function and social confidence. 

PMID- 26199523
TI  - Orthodontic Microimplants Assisted Intrusion of Supra-erupted Maxillary Molar
      Enabling Osseointegrated Implant Supported Mandibular Prosthesis: Case Reports.
AB  - Loss of mandibular molars, when not replaced in time, are usually associated with
      overeruption of maxillary molars. To provide prosthetic replacement for missing
      lower posteriors, over erupted maxillary teeth have been intruded in past with
      great difficulty in adults with conventional orthodontics, along with associated
      problems of root resorption. Currently orthodontic microimplants provide stable
      intraoral anchorage, allow predictable maxillary molar intrusion enabling
      reestablishment of functional posterior occlusion with mandibular implant
      supported prosthesis, thereby reducing need for prosthetic crown reduction in
      maxillary arch. The added advantage of microimplant is it enables use of
      sectional appliance in area of concern instead of full arch bracketed appliance
      which an adult may not accept. The case reports demonstrates, overerupted
      maxillary molars were intruded using orthodontic microimplants to enable
      prosthetic rehabilitation of mandibular dentition by osseointegrated implant
      supported prosthesis. The second case report also demonstrates use of CBCT scan
      in planning and execution. 

PMID- 26199524
TI  - The Use of Implants to Improve Removable Partial Denture Function.
AB  - The oral rehabilitation with conventional removable partial dentures in Kennedy
      class I patients allows continuous bone resorption, dislodgment of the prosthesis
      during the mastication caused by the resilience of the mucosa, and rotation of
      the prosthesis. Thus, the associations of distal implants become an attractive
      modality of treatment for these patients. This case report presented an
      association of removable partial dentures, milled crowns and osseointegrated
      implants to rehabilitate a partial edentulous patient. A removable partial
      denture associated with implants and metal-ceramic milled crowns can offer
      excellent esthetics, and will improve function and biomechanics, at a reduced
      cost. 

PMID- 26199525
TI  - The Ocular Prosthesis: A Novel Technique Using Digital Photography.
AB  - Loss of an eye can cause a significant psychological and emotional disturbance to
      any patient. An ocular prosthesis helps to re-establish the physical and mental
      well-being of the patient. This article describes a novel technique along with a
      case report for fabricating a predictable, esthetic and well-fitting custom-made
      ocular prosthesis in an attempt to avoid costly and time consuming procedures
      that may be required in other methods. 

PMID- 26199526
TI  - Oral Appliance for the Treatment of Severe Obstructive Sleep Apnea in Edentulous
      Patient.
AB  - Oral appliances have attracted interest for the treatment of mild and moderate
      obstructive sleep apnea (OSA) and the mandibular repositioning device (MRD) or a
      tongue-retainer device (TRD) is usually indicated to increase the upper air
      space. Describes a combination of MRD (with 60 % maximum mandibular protrusion)
      and TRD to treat severe OSA. Polysomnography (PSG) and two questionnaires: the
      Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI)
      evaluated the sleep pattern in two times (after and before the use of oral
      appliance). The initial PSG exam was compatible with diagnoses severe OSA and the
      Apnea-Hypopnea Index was 40.4, and 54 % oxygen saturation -spO(2). The ESS and
      PSQI scores were 11 and 6, respectively. After she began wearing the device she
      stopped snoring, her Apnea-Hypopnea Index decreased to 17.6, presented a sleep
      efficiency of 81.6 % and had a 77 % spO(2). The ESS and PSQI scores dropped to
      three. MRD in association with the tongue-retainer was effective in reducing the
      severity of the apnea for this edentulous patient. 

PMID- 26199527
TI  - Prosthetic Rehabilitation of Amputated Thumb: A Simplified Approach.
AB  - This case report presents a case of prosthetic rehabilitation of an amputated
      thumb. It emphasizes that prosthetic replacement is a better option for aesthetic
      and psychological improvement, particularly in cases where the victim is
      unwilling to undergo complicated surgical procedures for reconstruction of thumb
      or where functioning of thumb cannot be restored even by multiple surgeries. In
      the present case, a 20 years old female patient, with missing thumb of her right
      hand was rehabilitated aesthetically by a non-invasive and cost effective
      prosthetic procedure by using heat temperature vulcanizing silicone material. The
      prosthesis (the thumb) was attached using medical adhesives. On 3 months recall
      appointment, no complications were observed. The prosthesis was in good shape and
      required no further intervention. The prosthetic thumb lacks the sensation of a
      normal or reconstructed thumb, although it does not require the multiple
      procedures of surgical reconstruction and the accompanying loss of time for
      rehabilitation and healing. 

PMID- 26199528
TI  - Prosthetic Rehabilitation of a Patient with Congenitally Deformed Ears.
AB  - Treacher Collins syndrome is a rare autosomal dominant congenital disorder
      characterized by craniofacial deformities and is found in about 1 in 50,000
      births. This is a bilaterally symmetrical abnormalities derived from the first
      and second brachial arches and the nasal placode. Unfortunately, many of the new
      surgical techniques are extensive and compromise the patient's quality of life,
      not only function and esthetics but also the psychological status of the patient.
      These problems require prompt rehabilitation with surgery or prosthetic
      rehabilitation. This article presents a procedure in the basic fabrication of a
      prosthetic ear by a three-piece die technique. 

PMID- 26199529
TI  - Biologic Foundation Restoration: A Natural Post And Core For Management.
AB  - Complicated crown fractures are a common outcome of dental trauma. Various
      treatment options are available for consideration. The preferred choice of
      treatment though, is determined by multiple factors associated with the nature of
      trauma itself. This case report highlights the management of a cervical crown
      fracture by modifying the clinical technique of an existing concept of the
      "Biologic Post and Core" and integrating it with current advances in adhesive
      technology, with an intention for preservation and reinforcement of residual
      tooth structure. The clinical success observed during subsequent patient recall
      has given reason for optimism in considering the employed method as a possible
      alternative to address this area of prosthetic concern. 

PMID- 26199530
TI  - Resilient Attachments as an Alternative to Conventional Cast Clasp Removable
      Partial Denture: 3-Year Follow-up.
AB  - The present clinical report describes the prosthodontic management for a patient
      with uncontrolled bleeding and diabetes mellitus treated with a maxillary
      complete denture and a mandibular partial fixed dental prosthesis designed to
      interface with a removable cast framework partial denture retained by 2 ERA
      attachments. This approach was undertaken to improve both retention and stability
      of the distal extension Kennedy Class I removable partial denture. The
      rehabilitation provided better anterior esthetics than if treated with a
      conventional clasp retained removable partial denture, by employing a simple,
      practical design and offering a significant biomechanical advantages, restoring
      both oral health and function. Thus, this treatment modality, involving an ERA
      system and transfixation in fixed crowns, is an effective treatment and can be
      indicated as a clinical alternative for edentulous and partially edentulous
      patients with systemic disorders or for patients in economic situations that
      might preclude implant-based rehabilitation. 

PMID- 26199531
TI  - Lip Bumper Prosthesis for an Acromegaly Patient: A Clinical Report.
AB  - Prosthetic rehabilitation is done to regain function, speech and esthetics. This
      article describes the treatment for an acromegaly patient with bony defect. Two
      piece magnet retained hollow lip bumper prosthesis was fabricated to reduce the
      weight of the denture and to attain esthetics. 

PMID- 26199532
TI  - Tooth Supported Overdenture Retained with Custom Attachments: A Case Report.
AB  - Overdenture is a favored treatment modality for elderly patients with few
      remaining teeth. Roots maintained under the denture base preserve the alveolar
      ridge, provide sensory feedback and improve the stability of the dentures.
      Furthermore, the use of copings and precision attachments on the remaining teeth
      enhances the retention of the denture. This clinical report describes a novel
      method of fabricating a tooth supported overdenture retained with custom made
      ball attachments using orthodontic separators as a female component. Customized
      ball attachments with orthodontic separators are a simple and cost effective
      alternative treatment to the use of prefabricated attachments for enhancing the
      retention of tooth supported overdentures. 

PMID- 26199533
TI  - A Sectional Splint for Maintaining Surgically Enhanced Vertical Height in an Oral
      Submucous Fibrosis Patient: A Case Report.
AB  - Oral submucous fibrosis (OSMF) is a chronic inflammatory disease that results in
      a progressive juxtaepithelial fibrosis of the oral soft tissues, causing an
      increasing difficulty in mouth opening, chewing, swallowing and speaking. It is
      regarded as a precancerous and potentially malignant condition. The fibrosis of
      oral mucosa leads to limited mouth opening and difficulty in mastication.
      Prosthetic rehabilitation of patients with OSMF offers a formidable challenge due
      to the restricted mouth opening. Management of the limited mouth opening is
      usually by surgery. Herein, we describe a procedure to maintain the increased
      mouth opening that is achieved through surgery. Maintaining this opening would
      make it easier for any further prosthetic rehabilitation at a later stage. 

PMID- 26199534
TI  - Rehabilitation of a Patient with Central Giant Cell Granuloma of Mandible by
      Iliac Graft, Bone Distraction and Implant Retained Telescopic Prosthesis: a Two
      Year Follow Up.
AB  - Giant cell granulomas of the jaws are lesions that arise either peripherally in
      periodontal ligament, mucoperiosteum, or centrally in the bone. Histologically,
      both peripheral and central giant cell granuloma are characterized by the
      presence of numerous multinucleated giant cells in a prominent fibrous stroma.
      Traditional treatment has been local curettage, although aggressive sub-types
      have a high tendency to recur. This case report describes the rehabilitation
      procedure of a patient with central giant cell granuloma of left side of
      mandible. Marginal resection of the lesion was done followed by reconstruction of
      the resected mandible with iliac graft. Distraction of bone was done since there
      was partial uptake of the fibula graft. Five implants were placed once the
      distraction was complete. The patient was rehabilitated with implant retained
      removable telescopic prosthesis. 

PMID- 26199535
TI  - Immediate Placement and Restoration of Implant in Periapical Infected Site in the
      Maxillary Esthetic Zone: A Case Report.
AB  - Immediate placement and restoration of the implant is a widely used protocol, but
      loading of implants in the site which is periapically infected is still not very
      popular. Very few studies have been conducted and its still in debate. The
      conventional protocol of placing implant and waiting for it to osseointegrate is
      time consuming and compromises patients esthetics and psychological comfort. This
      report presents a case of immediate placement and restoration of implant in the
      region with periapical infection. 

PMID- 26199536
TI  - Craniofacial Prosthetic Reconstruction Using Polymethyl Methacrylate Implant: A
      Case Report.
AB  - Large cranial defects of complex geometric shapes are challenging to reconstruct.
      The cranial implants has to be fabricated prior to the cranioplastic surgery. The
      ideal material for cranial implant has to be inert, light weight, easy to fit and
      adaptable to the defect, offering the best aesthetic and functional results. Here
      is a clinical case report of a patient who was operated for osteomyelitis in the
      parieto-temporal region. The defect was reconstructed with heat cure
      polymethylmethacrylate (PMMA). Operative closure of the defect was facilitated
      with ligature titanium wires with minimal prosthesis contouring. The heat cure
      PMMA cranial implant is a safe, easy and economic alternative with great
      adaptability to cranial vault defects. The cosmetic results in this patient was
      excellent. No post-operative complications occurred. 

PMID- 26199537
TI  - Dental Implant Placement using C-arm CT Real Time Imaging System: A Case Report.
AB  - C-arm computed tomography (CT) is a new and innovative imaging technique. In
      combination with two-dimensional fluoroscopic or radiographic imaging,
      information provided by three-dimensional C-arm real time imaging can be valuable
      for therapy planning, guidance and outcome assessment in dental implant
      placement. This paper reports a case of two dental implant placement using Artis
      zee C-arm CT system first time in field of implantology. 

PMID- 26199538
TI  - A Simplified and Easy Approach for the Fabrication of Nasal Prosthesis: A
      Clinical Report.

PMID- 26199539
TI  - Treating Dehiscence During Implant Placement and Loading on Angled Abutment in
      Maxillary Lateral Incisor Region: A Case Report.
AB  - The primary factor causing recession is the morphology and anatomy of the
      dentition. The facial bony plate overlying the root is usually very thin. The
      complete absence of bone over the facial root surface is referred to as
      dehiscence. Such buccal bone defects in case of implant dentistry threaten the
      survival of dental implant. Many surgical techniques are introduced to enhance
      alveolar bone volume for placing the dental implants. Guided bone regeneration
      (GBR) is one such established surgical technique for correcting buccal dehiscence
      defects, along with the use of various barrier membranes for the same. This case
      report describes an implant placement in the maxillary left lateral incisor
      region showing dehiscence on the labial cortical plate, along with bone graft and
      GTR membrane. 

PMID- 26199540
TI  - Zirconia Intra Mucosal Inserts as a Retentive Aid for Maxillary Complete
      Dentures: A Case Report.
AB  - Complete dentures fabricated for edentulous patients with resorbed ridges
      generally have compromised retention and stability. The use of intramucosal
      inserts in order to aid retention of a maxillary denture has been reported in the
      past. Zirconia is a tissue compatible biomaterial whose scope and application in
      dentistry is on the rise. This paper reports the fabrication of zirconia
      intramucosal inserts and the technique of its incorporation in the maxillary
      complete denture in order to enhance retention, stability and thereby oral
      function. 

PMID- 26199541
TI  - Mandibular Overdenture Retained by Magnetic Assembly: A Clinical tip.
AB  - The preservation of remaining root structure and alveolar bone covering them with
      denture has been used since many years. Tooth-retained overdentures transfer
      occlusal forces to the alveolar bone through the periodontal ligament of the
      retained tooth roots and thereby prevent bone resorption. Applications of magnets
      in overdenture technique has been widely used in dentistry in the field of
      prosthodontics, as they can be manufactured in small dimensions as retentive
      devices for complete denture, removable partial dentures, obturators and
      maxillofacial prosthesis. This article presents a simple and efficient method of
      fabrication of mandibular over denture retained by magnets in a patient whose
      mandibular residual ridge is severely resorbed with few remaining teeth and
      maxillary conventional removable partial denture. Mandibular over denture
      retained by magnets assembly consist of magnet and coping with keeper on
      remaining tooth structure to rehabilitate the patient since magnetic attachments
      can provide support, stability and retention. 

PMID- 26199542
TI  - A Simple Technique to Fabricate Custom Made Occlusal Plane Template.
AB  - The plane of occlusion represents the average curvature of the occlusal surfaces
      of anterior and posterior teeth rather than a flat surface. An anteroposterior
      curve, the curve of Spee and the mediolateral curve, the curve of Wilson
      determine the position of posterior teeth. Management of patients with uneven
      occlusal plane is an essential step for the long term success of the treatment.
      Devices, like occlusal plane analyzers, are routinely used to evaluate the
      occlusal problems and help improve the situation. Yurkstas metal occlusal
      template is a device frequently used to determine proper occlusal plane. A simple
      procedure to fabricate a transparent occlusal plane template is described in this
      article. This occlusal template overcomes the major disadvantage i.e. non
      transparency of the Yurkstas metal occlusal template. 

PMID- 26199543
TI  - Easy Accurate Transfer of the Sculpted Soft Tissue Contours to the Working Cast:
      A Clinical Tip.
AB  - Tooth replacement in the esthetic zone presents a myriad of challenges for the
      clinician. An ovate pontic accurately duplicates the emergence profile of the
      natural tooth it replaces in order to provide an esthetic, yet cleansable
      prosthesis. The accurate transfer of this sculpted tissue beneath the pontic of
      the provisional restoration is critical to provide the dental laboratory
      technician with the necessary information to fabricate a definitive restoration
      with an appropriate emergence profile. This article presents an innovative,
      simple and convenient impression technique for easy and accurate transfer of the
      tissue contours to the working cast, avoiding tissue collapse and tissue
      compression produced due to the impression material. 

PMID- 26199544
TI  - A Simple Technique to Fabricate a Facial Moulage with a Prefabricated Acrylic
      Stock Tray: A Clinical Innovation.
AB  - An accurate facial moulage helps in understanding the orientation and proper
      position of the facial prosthesis relative to other facial landmarks even in the
      absence of the patient. To make impression for fabricating facial moulage
      previously described techniques in literature made use of elastomeric impression
      material, alginate, and dental plaster directly over the patient's face to obtain
      the moulage which have their own disadvantages. Taking these into consideration a
      novel clinical technique is described herein to fabricate an acrylic stock tray
      for making accurate impression and to support the impression material while
      setting and pouring. 

PMID- 26199545
TI  - "Split Cast Mounting: Review and New Technique".
AB  - For the fabrication of a prosthesis, the Prosthodontist meticulously performs all
      the steps. The laboratory technician then make every effort/strives to perform
      the remaining lab procedures. However when the processed dentures are remounted
      on the articulator, some changes are seen. These changes may be divided into two
      categories: Pre-insertion and post-insertion changes, which deal with the
      physical properties of the materials involved (Parker, J Prosthet Dent 31:335
      342, 1974). Split cast mounting is the method of mounting casts on the
      articulator. It is essentially a maxillary cast constructed in two parts with a
      horizontal division. The procedure allows for the verification of the accuracy of
      the initial mounting and the ease of removal and replacement of the cast. This
      provides a precise means of correcting the changes in occlusion occurring as a
      result of the processing technique (Nogueira et al., J Prosthet Dent 91:386-388,
      2004). Instability of the split mounting has always been a problem to the
      Prosthodontist thereby limiting its use. There are various materials mentioned in
      the literature. The new technique by using Dowel pins and twill thread is very
      easy, cheaper and simple way to stabilize the split mounting. It is useful and
      easy in day to day laboratory procedures. The article presents different methods
      of split cast mounting and the new procedure using easily available materials in
      prosthetic laboratory. 

PMID- 26199546
TI  - Stabilizing the Carbon Marker During Surveying: An Innovative Technique.
AB  - Dental surveyor has been defined as an instrument used to determine the relative
      parallelism of two or more surfaces of the teeth or other parts of the cast of a
      dental arch. Therefore the primary purpose of surveying is to identify the
      modifications of oral structures that are necessary to fabricate a removable
      partial denture that will have a successful prognosis. It is the modification of
      tooth surfaces to accommodate placement of the component parts of the partial
      denture in their designated ideal position on abutment teeth that facilitates
      this prognosis. Routinely, during marking the survey line, the carbon marker
      breaks many a times, as it is somehow brittle in structure, even after holding it
      in the metal sheath. This unnecessarily lengthens the working time of the
      operator as well as laboratory personnel. In the above mentioned new technique,
      the plastic refill sheath holds the carbon marker easily and securely. This
      serves the marking on the cast without breakage of carbon marker, thus saves the
      operator's time. The plastic refill sheath is easily available and economical. 

PMID- 26199547
TI  - Retraction Note to: Stem Cell Mediated Tooth Regeneration: New Vistas in
      Dentistry.
AB  - [This retracts the article DOI: 10.1007/s13191-011-0110-9.]. 

PMID- 26199548
TI  - A Tender Pulsatile Mass in a Patient with Splenomegaly.

PMID- 26199549
TI  - 20(S)-Protopanaxatriol inhibits release of inflammatory mediators in
      immunoglobulin E-mediated mast cell activation.
AB  - BACKGROUND: Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal
      metabolite of ginseng saponins, was investigated in guinea pig lung mast cells
      and mouse bone marrow-derived mast cells activated by a specific antigen/antibody
      reaction. METHODS: Increasing concentrations of PPT were pretreated 5 min prior
      to antigen stimulation, and various inflammatory mediator releases and their
      relevant cellular signaling events were measured in those cells. RESULTS: PPT
      dose-dependently reduced the release of histamine and leukotrienes in both types
      of mast cells. Especially, in activated bone marrow-derived mast cells, PPT
      inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and
      phospholipase A2 (PLA2), as well as the activities of various protein kinase C
      isoforms, mitogen-activated protein kinases, PLA2, and transcription factors
      (nuclear factor-kappaB and activator protein-1). CONCLUSION: PPT reduces the
      release of inflammatory mediators via inhibiting multiple cellular signaling
      pathways comprising the Ca(2+) influx, protein kinase C, and PLA2, which are
      propagated by Syk activation upon allergic stimulation of mast cells.

PMID- 26199550
TI  - Ginsenoside Rb1 ameliorates liver fat accumulation by upregulating perilipin
      expression in adipose tissue of db/db obese mice.
AB  - BACKGROUND: Ginsenoside Rb1 (G-Rb1), the major active constituent of ginseng,
      improves insulin sensitivity and exerts antidiabetic effects. We tested whether
      the insulin-sensitizing and antidiabetic effects of G-Rb1 results from a
      reduction in ectopic fat accumulation, mediated by inhibition of lipolysis in
      adipocytes. METHODS: Obese and diabetic db/db mice were treated with daily doses
      of 20 mg/kg G-Rb1 for 14 days. Hepatic fat accumulation was evaluated by
      measuring liver weight and triglyceride content. Levels of blood glucose and
      serum insulin were used to evaluate insulin sensitivity in db/db mice. Lipolysis
      in adipocytes was evaluated by measuring plasma-free fatty acids and glycerol
      release from 3T3-L1 adipocytes treated with G-Rb1. The expression of relevant
      genes was analyzed by western blotting, quantitative real-time polymerase chain
      reaction, and enzyme-linked immunosorbent assay kit. RESULTS: G-Rb1 increased
      insulin sensitivity and alleviated hepatic fat accumulation in obese diabetic
      db/db mice, and these effects were accompanied by reduced liver weight and
      hepatic triglyceride content. Furthermore, G-Rb1 lowered the levels of free fatty
      acids in obese mice, which may contribute to a decline in hepatic lipid
      accumulation. Corresponding to these results, G-Rb1 significantly suppressed
      lipolysis in 3T3-L1 adipocytes and upregulated the perilipin expression in both
      3T3-L1 adipocytes and mouse epididymal fat pads. Moreover, G-Rb1 increased the
      level of adiponectin and reduced that of tumor necrosis factor-alpha in obese
      mice, and these effects were confirmed in 3T3-L1 adipocytes. CONCLUSION: G-Rb1
      may improve insulin sensitivity in obese and diabetic db/db mice by reducing
      hepatic fat accumulation and suppressing adipocyte lipolysis; these effects may
      be mediated via the upregulation of perilipin expression in adipocytes.

PMID- 26199551
TI  - Ginseng total saponin attenuates myocardial injury via anti-oxidative and anti
      inflammatory properties.
AB  - BACKGROUND: Ginseng total saponin (GTS) contains various ginsenosides. These
      ginsenosides are widely used for treating cardiovascular diseases in Asian
      communities. The aim of this study was to study the effects of GTS on cardiac
      injury after global ischemia and reperfusion (I/R) in isolated guinea pig hearts.
      METHODS: Animals were subjected to normothermic ischemia for 60 minutes, followed
      by 120 minutes of reperfusion. GTS significantly increased aortic flow, coronary
      flow, and cardiac output. Moreover, GTS significantly increased left ventricular
      systolic pressure and the maximal rate of contraction (+dP/dt max) and relaxation
      (-dP/dt max). In addition, GTS has been shown to ameliorate electrocardiographic
      changes such as the QRS complex, QT interval, and RR interval. RESULTS: GTS
      significantly suppressed the biochemical parameters (i.e., lactate dehydrogenase,
      creatine kinase-MB fraction, and cardiac troponin I levels) and normalized the
      oxidative stress markers (i.e., malondialdehyde, glutathione, and nitrite). In
      addition, GTS also markedly inhibits the expression of interleukin-1beta (IL
      1beta), IL-6, and nuclear factor-kappaB, and improves the expression of IL-10 in
      cardiac tissue. CONCLUSION: These data indicate that GTS mitigates myocardial
      damage by modulating the biochemical and oxidative stress related to cardiac I/R
      injury.

PMID- 26199552
TI  - Induction of systemic resistance in Panax ginseng against Phytophthora cactorum
      by native Bacillus amyloliquefaciens HK34.
AB  - BACKGROUND: Korean ginseng (Panax ginseng Meyer) is a perennial herb prone to
      various root diseases, with Phytophthora cactorum being considered one of the
      most dreaded pathogens. P. cactorum causes foliar blight and root rot. Although
      chemical pesticides are available for disease control, attention has been shifted
      to viable, eco-friendly, and cost-effective biological means such as plant growth
      promoting rhizobacteria (PGPR) for control of diseases. METHODS: Native Bacillus
      amyloliquefaciens strain HK34 was isolated from wild ginseng and assessed as a
      biological control agent for ginseng. Leaves from plants treated with HK34 were
      analyzed for induced systemic resistance (ISR) against P. cactorum in square
      plate assay. Treated plants were verified for differential expression of defense
      related marker genes using quantitative reverse transcription polymerase chain
      reaction. RESULTS: A total of 78 native rhizosphere bacilli from wild P. ginseng
      were isolated. One of the root-associated bacteria identified as B.
      amyloliquefaciens strain HK34 effectively induced resistance against P. cactorum
      when applied as soil drench once (99.1% disease control) and as a priming
      treatment two times in the early stages (83.9% disease control). A similar result
      was observed in the leaf samples of plants under field conditions, where the
      percentage of disease control was 85.6%. Significant upregulation of the genes
      PgPR10, PgPR5, and PgCAT in the leaves of plants treated with HK34 was observed
      against P. cactorum compared with untreated controls and only pathogen-treated
      plants. CONCLUSION: The results of this study indicate HK34 as a potential
      biocontrol agent eliciting ISR in ginseng against P. cactorum.

PMID- 26199553
TI  - Preparation of minor ginsenosides C-Mc, C-Y, F2, and C-K from American ginseng
      PPD-ginsenoside using special ginsenosidase type-I from Aspergillus niger g.848.
AB  - BACKGROUND: Minor ginsenosides, those having low content in ginseng, have higher
      pharmacological activities. To obtain minor ginsenosides, the biotransformation
      of American ginseng protopanaxadiol (PPD)-ginsenoside was studied using special
      ginsenosidase type-I from Aspergillus niger g.848. METHODS: DEAE
      (diethylaminoethyl)-cellulose and polyacrylamide gel electrophoresis were used in
      enzyme purification, thin-layer chromatography and high performance liquid
      chromatography (HPLC) were used in enzyme hydrolysis and kinetics; crude enzyme
      was used in minor ginsenoside preparation from PPD-ginsenoside; the products were
      separated with silica-gel-column, and recognized by HPLC and NMR (Nuclear
      Magnetic Resonance). RESULTS: The enzyme molecular weight was 75 kDa; the enzyme
      firstly hydrolyzed the C-20 position 20-O-beta-D-Glc of ginsenoside Rb1, then the
      C-3 position 3-O-beta-D-Glc with the pathway Rb1->Rd->F2->C-K. However, the
      enzyme firstly hydrolyzed C-3 position 3-O-beta-D-Glc of ginsenoside Rb2 and Rc,
      finally hydrolyzed 20-O-L-Ara with the pathway Rb2->C-O->C-Y->C-K, and Rc->C-Mc1
      >C-Mc->C-K. According to enzyme kinetics, K m and V max of Michaelis-Menten
      equation, the enzyme reaction velocities on ginsenosides were Rb1 > Rb2 > Rc >
      Rd. However, the pure enzyme yield was only 3.1%, so crude enzyme was used for
      minor ginsenoside preparation. When the crude enzyme was reacted in 3% American
      ginseng PPD-ginsenoside (containing Rb1, Rb2, Rc, and Rd) at 45 degrees C and pH
      5.0 for 18 h, the main products were minor ginsenosides C-Mc, C-Y, F2, and C-K;
      average molar yields were 43.7% for C-Mc from Rc, 42.4% for C-Y from Rb2, and
      69.5% for F2 and C-K from Rb1 and Rd. CONCLUSION: Four monomer minor ginsenosides
      were successfully produced (at low-cost) from the PPD-ginsenosides using crude
      enzyme.

PMID- 26199554
TI  - American ginseng significantly reduced the progression of high-fat-diet-enhanced
      colon carcinogenesis in Apc (Min/+) mice.
AB  - BACKGROUND: Colorectal cancer (CRC) is a leading cause of death worldwide.
      Chronic gut inflammation is recognized as a risk factor for tumor development,
      including CRC. American ginseng is a very commonly used ginseng species in the
      West. METHODS: A genetically engineered Apc (Min/+) mouse model was used in this
      study. We analyzed the saponin composition of American ginseng used in this
      project, and evaluated its effects on the progression of high-fat-diet-enhanced
      CRC carcinogenesis. RESULTS: After oral ginseng administration (10-20 mg/kg/d for
      up to 32 wk), experimental data showed that, compared with the untreated mice,
      ginseng very significantly reduced tumor initiation and progression in both the
      small intestine (including the proximal end, middle end, and distal end) and the
      colon (all p < 0.01). This tumor number reduction was more obvious in those mice
      treated with a low dose of ginseng. The tumor multiplicity data were supported by
      body weight changes and gut tissue histology examinations. In addition,
      quantitative real-time polymerase chain reaction analysis showed that compared
      with the untreated group, ginseng very significantly reduced the gene expression
      of inflammatory cytokines, including interleukin-1alpha (IL-1alpha), IL-1beta, IL
      6, tumor necrosis factor-alpha, granulocyte-colony stimulating factor, and
      granulocyte-macrophage colony-stimulating factor in both the small intestine and
      the colon (all p < 0.01). CONCLUSION: Further studies are needed to link our
      observed effects to the actions of the gut microbiome in converting the parent
      ginsenosides to bioactive ginseng metabolites. Our data suggest that American
      ginseng may have potential value in CRC chemoprevention.

PMID- 26199555
TI  - Antimelanogenic effect of ginsenoside Rg3 through extracellular signal-regulated
      kinase-mediated inhibition of microphthalmia-associated transcription factor.
AB  - BACKGROUND: Panax ginseng has been used to prolong longevity and is believed to
      be useful for improving skin complexion. Ginsenosides are the most active
      components isolated from ginseng, and ginsenoside Rg3 (G-Rg3) in particular has
      been demonstrated to possess antioxidative, antitumorigenic, and anti
      inflammatory properties. The aim of this study was to examine the ability of G
      Rg3 to inhibit melanogenesis. METHODS: The effects of G-Rg3 on melanin contents
      and the protein levels of tyrosinase, microphthalmia-associated transcription
      factor (MITF), and tyrosinase-related protein 1 (TRP1) were evaluated.
      Melanogenesis-regulating signaling molecules such as Akt and extracellular signal
      regulated kinase (ERK) were also examined to explore G-Rg3-induced
      antimelanogenic mechanisms. RESULTS: G-Rg3 was found to significantly inhibit the
      synthesis of melanin in normal human epidermal melanocytes and B16F10 cells in a
      dose-dependent manner. The activity of cellular tyrosinase and the expression of
      MITF, tyrosinase, and TRP1 were all reduced, whereas ERK was strongly activated.
      PD98059 (a specific inhibitor of ERK) attenuated the G-Rg3-induced inhibition of
      melanin synthesis and tyrosinase activity. CONCLUSION: Taken together, these
      results showed that G-Rg3 induces the activation of ERK, which accounts for its
      antimelanogenic effects. G-Rg3 may be a promising safe skin-whitening agent,
      adding to the long list of uses of P. ginseng for the enhancement of skin beauty.

PMID- 26199556
TI  - Effects of Korean Red Ginseng extract on busulfan-induced dysfunction of the male
      reproductive system.
AB  - BACKGROUND: Anticancer agents induce a variety of adverse effects when
      administered to cancer patients. Busulfan is a known antileukemia agent. When
      administered for treatment of leukemia in young patients, busulfan could cause
      damage to the male reproductive system as one of its adverse effects, resulting
      in sterility. METHODS: We investigated the effects of Korean Red Ginseng extract
      (KRGE) on busulfan-induced damage and/or dysfunction of the male reproductive
      system. RESULTS: We found that administration of busulfan to mice: decreased
      testis weight; caused testicular histological damage; reduced the total number of
      sperm, sperm motility, serum testosterone concentration; and eventually, litter
      size. Preadministration of KRGE partially attenuated various busulfan-induced
      damages to the male reproductive system. These results indicate that KRGE has a
      protective effect against busulfan-induced damage to the male reproduction
      system. CONCLUSION: The present study shows a possibility that KRGE could be
      applied as a useful agent to prevent or protect the male reproductive system from
      the adverse side effects induced by administration of anticancer agents such as
      busulfan.

PMID- 26199557
TI  - Administration of red ginseng ameliorates memory decline in aged mice.
AB  - BACKGROUND: It has been known that ginseng can be applied as a potential
      nutraceutical for memory impairment; however, experiments with animals of old age
      are few. METHODS: To determine the memory enhancing effect of red ginseng,
      C57BL/6 mice (21 mo old) were given experimental diet pellets containing 0.12%
      red ginseng extract (approximately 200 mg/kg/d) for 3 mo. Young and old mice (4
      mo and 21 mo old, respectively) were used as the control group. The effect of red
      ginseng, which ameliorated memory impairment in aged mice, was quantified using Y
      maze test, novel objective test, and Morris water maze. Red ginseng ameliorated
      age-related declines in learning and memory in older mice. In addition, red
      ginseng's effect on the induction of inducible nitric oxide synthase and
      proinflammatory cytokines was investigated in the hippocampus of aged mice.
      RESULTS: Red ginseng treatment suppressed the production of age-processed
      inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-alpha,
      and interleukin-1beta expressions. Moreover, it was observed that red ginseng had
      an antioxidative effect on aged mice. The suppressed glutathione level in aged
      mice was restored with red ginseng treatment. The antioxidative-related enzymes
      Nrf2 and HO-1 were increased with red ginseng treatment. CONCLUSION: The results
      revealed that when red ginseng is administered over long periods, age-related
      decline of learning and memory is ameliorated through anti-inflammatory activity.

PMID- 26199558
TI  - Red ginseng extract blocks histamine-dependent itch by inhibition of H1R/TRPV1
      pathway in sensory neurons.
AB  - BACKGROUND: Korean Red Ginseng-a steamed root of Panax ginseng Meyer-has long
      been used as a traditional medicine in Asian countries. Its antipruritic effect
      was recently found, but no molecular mechanisms were revealed. Thus, the current
      study focused on determining the underlying molecular mechanism of Korean Red
      Ginseng extract (RGE) against histamine-induced itch at the peripheral sensory
      neuronal level. METHODS: To examine the antipruritic effect of RGE, we performed
      in vivo scratching behavior test in mice, as well as in vitro calcium imaging and
      whole-cell patch clamp experiments to elucidate underlying molecular mechanisms.
      RESULTS: The results of our in vivo study confirmed that RGE indeed has an
      antipruritic effect on histamine-induced scratching in mice. In addition, RGE
      showed a significant inhibitory effect on histamine-induced responses in primary
      cultures of mouse dorsal root ganglia, suggesting that RGE has a direct
      inhibitory effect on sensory neuronal level. Results of further experiments
      showed that RGE inhibits histamine-induced responses on cells expressing both
      histamine receptor subtype 1 and TRPV1 ion channel, indicating that RGE blocks
      the histamine receptor type 1/TRPV1 pathway in sensory neurons, which is
      responsible for histamine-dependent itch sensation. CONCLUSION: The current study
      found for the first time that RGE effectively blocks histamine-induced itch in
      peripheral sensory neurons. We believe that the current results will provide an
      insight on itch transmission and will be helpful in understanding how RGE exerts
      its antipruritic effects.

PMID- 26199559
TI  - Chemoprevention of chemical-induced skin cancer by Panax ginseng root extract.
AB  - BACKGROUND: Cancer has emerged as a major health problem globally as a
      consequence to the increased longevity of the population, changing the
      environment and life style. Chemoprevention is a new and promising strategy for
      reducing cancer burden. Recently, some natural products have been identified for
      their chemopreventive activity to reduce the cancer incidence. Ginseng is known
      for its potential to treat various ailments in human beings. The present study
      was designed to explore the anticancer and antioxidative potential of Panax
      ginseng against chemical-induced skin carcinogenesis in mammals. METHODS: Skin
      tumors were induced in Swiss albino mice by a single topical application of 7,12
      dimethylbenz(a)anthracene (100 MUg/100 MUL acetone) and, 2 wks later, promoted by
      repeated applications of croton oil (thrice in a wk in 1% acetone) till the end
      of the experiment (i.e., 16 wk). Hydroalcoholic ginseng root extract at a dose of
      25 mg/kg body weight/d was orally administered at the peri-initiation,
      postinitiation, and peri-post-initiation stages. RESULTS: Ginseng root extract
      treatment caused a significant reduction in tumor incidence, cumulative number of
      tumors, tumor yield, and tumor burden, as compared to the 7,12
      dimethylbenz(a)anthracene-croton oil-treated control group. Further, biochemical
      assays revealed a significant enhancement in the levels of reduced glutathione,
      superoxide dismutase, catalase, vitamin C, and total proteins but a significant
      reduction in lipid peroxidation levels in both the liver and skin with ginseng
      root extract treatment, as compared to carcinogen-treated control group.
      CONCLUSION: These results suggest that P. ginseng has the potential to become a
      pivotal chemopreventive agent that can reduce cancer in mammals.

PMID- 26199560
TI  - Effects of steaming on saponin compositions and antiproliferative activity of
      Vietnamese ginseng.
AB  - BACKGROUND: Steaming of ginseng is known to change its chemical composition and
      biological activity. This study was carried out to investigate the effect of
      different steaming time-scales on chemical constituents and antiproliferative
      activity of Vietnamese ginseng (VG). METHODS: VG was steamed at 105 degrees C for
      2-20 h. Its saponin constituents and antiproliferative activity were studied. The
      similarity of chemical compositions between steamed samples at 105 degrees C and
      120 degrees C were compared. RESULTS: Most protopanaxadiol and protopanaxatriol
      ginsenosides lost the sugar moiety at the C-20 position with 10-14 h steaming at
      105 degrees C and changed to their less polar analogues. However, ocotillol (OCT)
      ginsenosides were reasonably stable to steaming process. Antiproliferative
      activity against A549 lung cancer cells was increased on steaming and reached its
      plateau after 12 h steaming. CONCLUSION: Steaming VG at 105 degrees C showed a
      similar tendency of chemical degradation to the steaming VG at 120 degrees C
      except the slower rate of reaction. Its rate was about one-third of the steaming
      at 120 degrees C.

PMID- 26199561
TI  - The inhibitory mechanism of crude saponin fraction from Korean Red Ginseng in
      collagen-induced platelet aggregation.
AB  - BACKGROUND: Korean Red Ginseng has been used as a traditional oriental medicine
      to treat illness and to promote health for several thousand years in Eastern
      Asia. It is widely accepted that ginseng saponins, ginsenosides, are the major
      active ingredients responsible for Korean Red Ginseng's therapeutic activity
      against many kinds of illness. Although the crude saponin fraction (CSF)
      displayed antiplatelet activity, the molecular mechanism of its action remains to
      be elucidated. METHODS: The platelet aggregation was induced by collagen, the
      ligand of integrin alphaIIbetaI and glycoprotein VI. The crude saponin's effects
      on granule secretion [e.g., calcium ion mobilization and adenosine triphosphate
      (ATP) release] were determined. The activation of mitogen-activated protein
      kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2
      (ERK1/2), c-Jun N-terminal kinases (JNKs), and p38 MAPK, and phosphoinositide 3
      kinase (PI3K)/Akt was analyzed by immunoblotting. In addition, the activation of
      integrin alphaIIbbetaIII was examined by fluorocytometry. RESULTS: CSF strongly
      inhibited collagen-induced platelet aggregation and ATP release in a
      concentration-dependent manner. It also markedly suppressed [Ca(2+)]i
      mobilization in collagen-stimulated platelets. Immunoblotting assay revealed that
      CSF significantly suppressed ERK1/2, p38, JNK, PI3K, Akt, and mitogen-activated
      protein kinase kinase 1/2 phosphorylation. In addition, our fraction strongly
      inhibited the fibrinogen binding to integrin alphaIIbbeta3. CONCLUSION: Our
      present data suggest that CSF may have a strong antiplatelet property and it can
      be considered as a candidate with therapeutic potential for the treatment of
      cardiovascular disorders involving abnormal platelet function.

PMID- 26199562
TI  - Whole Lung Irradiation in Adults with Metastatic Ewing Sarcoma: Practice Patterns
      and Implications for Treatment.
AB  - Background. Whole lung irradiation (WLI) is a standard treatment component for
      children with metastatic Ewing Sarcoma (ES), but data on WLI for adults are
      sparse. Design. An email survey was sent to expert sarcoma-dedicated oncologists
      worldwide: An adult with excellent performance status presents with primary ES in
      the leg and multiple pulmonary metastases. The patient achieves complete
      radiographic response after chemotherapy and resection of the primary. Would you
      give bilateral WLI to (1) this adult patient?, (2) this patient if 20 years old
      (yo)?, (3) this patient if 45 yo?, or (4) this patient if 60 yo? Results. 38
      experts responded, including 24 adult, 1 adolescent young adult, and 13 pediatric
      oncologists. 63%, 63%, 62%, and 50% of respondents offered WLI to the adult, 20
      year-old, 45-year-old, and 60-year-old, respectively. Pediatric oncologists more
      likely endorsed WLI across all ages including the adult (P = 0.01), 20-year-old
      (P = 0.005), 45-year-old (P = 0.01), and 60-year-old (P = 0.08). There were no
      significant differences between medical and radiation oncologists or between
      European/Australian and American providers. Conclusions. Almost two-thirds of
      experts surveyed supported WLI for adults with metastatic ES up to age 45 and
      half supported WLI for a 60-year-old. Continued collaboration across adult and
      pediatric oncology is needed to define evidence-based strategies across the age
      spectrum. 

PMID- 26199563
TI  - Hormone therapy in combination with radiotherapy in the treatment of prostate
      cancer: why and in which group of patients?
AB  - In recent years, significant development in the treatment of prostate cancer has
      taken place. One of the most documented methods of treatment in patients
      characterised by a high risk of progression is a combination of radiotherapy (RT)
      with long-term hormone therapy (HT). In this group of patients, neither RT alone
      nor HT alone allows satisfactory outcomes to be achieved, and therefore as
      monotherapy they are not recommended as optimal methods of treatment. In this
      review, we summarise arguments for combining radiotherapy with hormonal therapy
      in high-risk prostate cancer, with an emphasis on the results of phase III
      trials. 

PMID- 26199565
TI  - Relationship between serotonin transporter gene polymorphism and constipation in
      cancer patients.
AB  - INTRODUCTION: To assess the potential association between serotonin transporter
      gene insertion/deletion polymorphism and the cancer-related constipation
      phenotype. MATERIAL AND METHODS: A total of 120 patients diagnosed with malignant
      solid tumors were subjected to genotyping. For the two groups - patients with
      constipation and constipation-free patients with non-gastrointestinal cancer, 60
      cases in each group - we collected the peripheral venous blood. We extracted
      genomic DNA, and used polymerase chain reaction (PCR) to analyze the serotonin
      transporter (5-HT) link polymorphic region (5-HTTLPR) polymorphism of the
      serotonin transporter gene. RESULTS: The frequency of S/S genotype in cancer
      patients with constipation was 66.67% (40/60), and the frequency of the S allele
      was 79.17% (95/120); the frequency of S/S genotype in cancer patients without
      constipation was 48.33% (29/60), and the frequency of the S allele was 65.83%
      (79/120). There was a significant difference between the two groups (p < 0.05).
      CONCLUSIONS: The presence of 5-HTTLPRS/S genotype and the S allele in patients
      with cancers probably carry an increased risk of constipation. However, its role
      as a cause of cancer-related constipation needs to be further investigated.

PMID- 26199564
TI  - Paraneoplastic syndromes in olfactory neuroblastoma.
AB  - Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of sinonasal tract,
      derived from olfactory epithelium. Unilateral nasal obstruction, epistaxis,
      sinusitis, and headaches are common symptoms. Olfactory neuroblastoma shows
      neuroendocrine differentiation and similarly to other neuroendocrine tumors can
      produce several types of peptic substances and hormones. Excess production of
      these substances can be responsible for different types of endocrinological
      paraneoplastic syndromes (PNS). Moreover, besides endocrinological, in ONB may
      also occur neurological PNS, caused by immune cross-reactivity between tumor and
      normal host tissues in the nervous system. Paraneoplastic syndromes in ONB
      include: syndrome of inappropriate ADH secretion (SIADH), ectopic ACTH syndrome
      (EAS), humoral hypercalcemia of malignancy (HHM), hypertension due to
      catecholamine secretion by tumor, opsoclonus-myoclonus-ataxia (OMA) and
      paraneoplastic cerebellar degeneration. Paraneoplastic syndromes in ONB tend to
      have atypical features, therefore diagnosis may be difficult. In this review, we
      described initial symptoms, patterns of presentation, treatment and outcome of
      paraneoplastic syndromes in ONB, reported in the literature. 

PMID- 26199566
TI  - EGFR and KRAS mutations in pulmonary pleomorphic carcinoma and their correlation
      with clinicopathologic features.
AB  - AIM OF THE STUDY: Pulmonary pleomorphic carcinoma (PPC) of the lung is a subset
      of poorly differentiated non-small cell lung cancers (NSCLCs). Because of its
      rarity, information on epidermal growth factor receptor (EGFR) and Kirsten rat
      sarcoma viral oncogene (KRAS) mutations is controversial and sparse. The aim was
      to investigate the two key oncogenes' characteristics and their correlation with
      clinical variables. MATERIAL AND METHODS: We retrospectively screened 110
      paraffin-embedded surgically resected specimens from patients with PPC. Of these,
      follow-up information was available for 48 patients. We then successfully
      analyzed 70 PPC samples and examined EGFR and KRAS mutation status by direct
      sequencing. The findings were correlated with a control group of patients with
      other NSCLCs. RESULTS: In our department, PPC comprised about 1.57% of surgical
      resected cases (110/6990). 37.4% of patients smoked. EGFR mutations were detected
      in 11 cases (15.7%), with a significantly higher frequency in women than men (p =
      0.011). KRAS mutations were detected in 10 cases (14.3%) and were more often
      found at age 65 or older (p = 0.02). Of interest, in PPC, all KRAS mutations
      occurred in never smokers. Also, most never smokers have transversion mutations
      (G->T) in PPCs and other NSCLCs. CONCLUSIONS: Our results demonstrated a similar
      EGFR and KRAS mutation rate in Chinese PPC patients. EGFR tyrosine kinase
      inhibitors may be a treatment option for PPCs with EGFR mutations. Of note, EGFR
      mutations in PPC were commonly identified in women; therefore women should be
      high-priority candidates for mutation screening.

PMID- 26199568
TI  - Genistein-induced mir-23b expression inhibits the growth of breast cancer cells.
AB  - AIM OF THE STUDY: Genistein, an isoflavonoid, plays roles in the inhibition of
      protein tyrosine kinase phosphorylation, induction of apoptosis, and cell
      differentiation in breast cancer. This study aims to induce cellular stress by
      exposing genistein to determine alterations of miRNA expression profiles in MCF-7
      cells. MATERIAL AND METHODS: XTT assay and trypan blue dye exclusion assays were
      performed to examine the cytotoxic effects of genistein treatment. Expressions of
      miRNAs were quantified using Real-Time Online RT-PCR. RESULTS: The IC50 dose of
      genistein was 175 MUM in MCF-7 cell, line and the cytotoxic effect of genistein
      was detected after 48 hours. miR-23b was found to be up-regulated 56.69 fold
      following the treatment of genistein. It was found that miR-23b was upregulated
      for MCF-7 breast cancer cells after genistein treatment. CONCLUSIONS: Up
      regulated ex-expression of miR-23b might be a putative biomarker for use in the
      therapy of breast cancer patients. miR-23b up-regulation might be important in
      terms of response to genistein.

PMID- 26199567
TI  - P27 expression in pleomorphic salivary gland adenoma.
AB  - AIM OF THE STUDY: This study aims to characterise alterations in the
      immunohistochemical expression of p27 in normal tissue of the salivary gland
      surrounding pleomorphic adenoma and in the tumour cells of pleomorphic adenoma.
      MATERIAL AND METHODS: A retrospective study of data including 120 cases of
      pleomorphic adenomas (66 female, 54 male) retrieved from the files of the Oral
      Pathology Departments of Aleppo University, Syria and Al-Farabi Dental and
      Nursing College. Immunohistochemical expression against p27 was examined in the
      selected cases. The percentage of p27-positive nuclei was semi-quantitatively
      assessed by two independent observers and scores were given. The statistical
      analysis included the use of descriptive statistics and proportional frequencies.
      RESULTS: The results showed that P27 nuclear staining with high staining
      (moderate to strong positive staining in more than 50% of nuclei, depending on
      the percentage of nuclei for the cells) was noted in tumour duct cells of
      pleomorphic adenoma in 90 (75%) cases out of 120, while 30 (25%) cases showed low
      staining (positive staining in less than 5% of nuclei, depending on the
      percentage of nuclei for the cells). CONCLUSIONS: Our data suggests that p27
      might have a minor role in the development of pleomorphic adenoma.

PMID- 26199569
TI  - Effect of beta-sitosterol on the expression of HPV E6 and p53 in cervical
      carcinoma cells.
AB  - AIM OF THE STUDY: In the absence of effective therapeutic strategies, cervical
      carcinoma continues to be second on the list of mortality rates of malignant
      tumours found in women. We investigated the effects of beta -sitosterol, a
      natural product isolated from traditional Chinese herbs, on Caski and HeLa
      cervical carcinoma cells. MATERIAL AND METHODS: Morphological changes were
      examined by light microscopy. Ultrastructures of Caski and HeLa cells treated
      with 20 umol/l beta-sitosterol were documented by scanning electron microscopy
      and transmission electron microscopy. Changes in mRNA and protein expression were
      quantified respectively using Real-Time qPCR and western blot methods. RESULTS:
      Treatment of Caski and HeLa cells with beta-sitosterol resulted in reduced
      expression of PCNA, indicative of an inhibitory effect on cell proliferation.
      This was associated with increased p53 mRNA levels and decreased amounts of HPV
      E6 transcripts. Expression of p53 and HPV E6 proteins followed a similar trend as
      that observed for the corresponding transcripts. Caski and HeLa cells treated
      with beta-sitosterol exhibited loss of cell surface microvilli, increased
      electron density of cell membrane, and decreased organelles. CONCLUSIONS: In
      conclusion, treatment of Caski and HeLa cells with beta-sitosterol significantly
      suppressed the expression of genes involved in cell proliferation and oncogenic
      transformation, while augmenting the expression of genes involved in apoptosis
      and tumour suppression. Ultrastuctural characterisation of Caski and HeLa cells
      treated with beta-sitosterol further confirmed the anti-proliferative and anti
      cancer activity of this natural product isolated from traditional Chinese herbs.

PMID- 26199570
TI  - The use of Yttrium-90 Ibritumomab Tiuxetan ((90)Y-IT) as a consolidation therapy
      in high-risk patients with diffuse large B-cell lymphoma ineligible for
      autologous stem-cell transplantation.
AB  - AIM OF THE STUDY: To evaluate the efficacy and safety of Yttrium-90 Ibritumomab
      Tiuxetan ((90)Y-IT) as a consolidation therapy in the management of DLBCL.
      MATERIAL AND METHODS: Patients with primary refractory or high-risk DLBCL (n =
      18), ineligible for autologous stem-cell transplantation, were included in a
      retrospective study performed at three centers by the Polish Lymphoma Research
      Group (PLRG). All patients (mean age 61, range 35-82) either didn't achieve a
      complete response or didn't complete the scheduled therapy due to its
      complications. Response rates (CR, PR, SD, PD) according to Cheson criteria,
      overall survival (OS), progression-free survival (PFS) and adverse effects of
      radioimmunotherapy were analyzed. RESULTS: Consolidation radioimmunotherapy
      increased the CR rate from 38% (n = 7) to 82% (n = 15). One patient remained in
      PR, one patient remained in SD, while one patient remained in PD. During a median
      follow-up of five years, 11 patients (62%) were alive with no recurrence, 4
      patients (22%) were alive with relapse while 3 patients (16%) died. There was no
      statistically significant difference in PFS between those in CR and those in PR
      before (90)Y-IT. CONCLUSIONS: Radioimmunotherapy is an effective consolidation
      therapy for high risk/refractory DLBCL patients and worthy of further
      investigation in prospective trials.

PMID- 26199571
TI  - The prognostic significance of tumor epidermal growth factor receptor (EGFR)
      expression change after neoadjuvant chemoradiation in patients with rectal
      adenocarcinoma.
AB  - AIM OF THE STUDY: The aim of this retrospective study was to determine the
      prognostic impact of epidermal growth factor receptor (EGFR) expression changes
      during neoadjuvant chemoradiotherapy in patients with locally advanced rectal
      cancer. MATERIAL AND METHODS: Fifty patients with locally advanced rectal cancer
      were evaluated. All the patients were administered the total dose of 44 Gy.
      Capecitabine has been concomitantly administered in the dose 825 mg/m(2) in two
      daily oral administrations. Surgery was indicated 4-8 weeks from the
      chemoradiotherapy completion. Epidermal growth factor receptor expression in the
      pretreatment biopsies and in the resected specimens was assessed with
      immunohistochemistry. RESULTS: All of 50 patients received radiotherapy without
      interruption up to the total planned dose. In 30 patients sphincter-saving
      surgery was performed, 20 patients underwent amputation of the rectum.
      Downstaging was described in 30 patients. Four patients have had complete
      pathologic remission. Twenty-six patients have had partial remission, the disease
      was stable in 15 patients. Progression was reported in 5 patients. The median
      disease-free survival was 64.9 months, median overall survival was 76.4 months.
      Increased EGFR expression was found in 12 patients (26.1%). A statistically
      significantly shorter overall survival (p < 0.0001) and disease-free survival (p
      < 0.0001) was found in patients with increased expression of EGFR compared with
      patients where no increase in the expression of EGFR during neoadjuvant
      chemoradiotherapy was observed. CONCLUSIONS: The overexpression of EGFR during
      neoadjuvant chemoradiotherapy for locally advanced rectal adenokarcinoma
      associated with significant shorter overall survival and disease free survival.

PMID- 26199572
TI  - Results of surgical management of renal cell carcinoma metastatic to the
      pancreas.
AB  - AIM OF THE STUDY: Metastases from renal cell carcinoma represent between 0.25%
      and 3.00% of all resected pancreatic tumours. The aim of this study was to review
      13 patients with renal cell carcinoma metastatic to the pancreas. MATERIAL AND
      METHODS: Clinical data, time from initial presentation, operative outcome, long
      term survival, tumour size, presence of lymphatic invasion, and surgical margin
      status were evaluated. RESULTS: The median age of the patients was 62 years (mean
      60.9). The median time for appearance of metastatic disease following resection
      of the primary tumour was 9 years (mean 8.38). Pancreatic metastases were located
      in the head of the pancreas in four patients, in the body in three, in the tail
      in two patients, and four patients had multiple pancreatic localisations. Four
      (30.7%) pancreatoduodenectomies, 5 (38.5%) distal resections, 2 (15.3%) total
      pancreatectomies, 1 (7.6%) enucleation, and 1 (7.6%) Roux duodenojejunostomy were
      performed. Two patients (15.3%) had postoperative complications. Operative
      mortality was 0%. Surgical margins were microscopically positive in 1 (8.3%)
      patient, and lymph nodes were positive in 2 (16.6%) patients. In our group of 7
      deceased patients the mean survival was 19 months (median 16 months).
      CONCLUSIONS: Renal cell carcinoma metastatic to the pancreas can occur several
      years after nephrectomy. In our series a large number of patients with occurrence
      of symptoms, advancement of tumours, metastases to lymph node, and positive
      margin were connected with short survival period. Early detection of primary
      tumour, long and thorough patient care, and radical resections give patients a
      chance for a prolonged life.

PMID- 26199574
TI  - The risk factors of toxicity during chemotherapy and radiotherapy in breast
      cancer patients according to the presence of BRCA gene mutation.
AB  - AIM OF THE STUDY: Treatment toxicity may decrease the treatment effectiveness due
      to the need to reduce the dose or increase the interval between cycles. The aim
      of this study was to distinguish the risk factors for treatment side effects in
      breast cancer patients and to assess the impact of BRCA1/2 mutations on the
      treatment toxicity. MATERIAL AND METHODS: The analysis was conducted on the
      medical history of 370 patients who were treated with anthracycline-based
      chemotherapy between 2006 and 2012 in the Clinical Oncology Department, Maria
      Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology in Gliwice in
      Poland (COI). All patients were tested for the presence of BRCA1 and BRCA2
      mutations. RESULTS: In the studied group 13% (48) of the patients were BRCA
      mutation carriers. Neutropaenia after the first cycle of chemotherapy occurred
      more commonly in mutation carriers compared to non-carriers (29% vs. 10%), p =
      0.0002. Radiotherapy acute skin toxicity was present in 3% of patients with
      similar rates in both groups, p = 0.950. Toxicity grade 3-4 was present more
      frequently in patients younger than 70 years (p = 0.02) of age, patients with
      viral hepatitis (p = 0.045), hypertension (p = 0.039), and cardiovascular disease
      (p = 0.044). Lower WBC count before treatment was observed more frequently in
      patients with neutropaenia (p = 0.002), especially in mutation carriers, p =
      0.0015. CONCLUSIONS: Risk factors for anthracycline-based chemotherapy side
      effects were: age below 70 years, lower WBC value at baseline, history of
      infectious diseases, hypertension, and cardiovascular comorbidity. The presence
      of BRCA mutations may be a risk factor for neutropaenia, but it did not affect
      radiotherapy toxicity.

PMID- 26199573
TI  - Preliminary results of tomotherapy for treatment of inoperable recurrent non
      small cell lung cancer at bronchial stump site after right pneumonectomy.
AB  - AIM OF THE STUDY: This study aimed to prospectively investigate the clinical
      outcomes of curative radical helical tomotherapy (HT) applied to recurrent non
      small cell lung cancer (NSCLC) at the bronchial stump site after right
      pneumonectomy. After right pneumonectomy, the heart shifted right laterally. The
      chambers of the heart closed with a recurrent mass at the bronchial stump were
      the right atrium and left atrium due to right shifting of the heart. The
      unfavorable bronchial stump recurrent cancer-heart geometry due to a right shift
      of the heart might serve as a reliable predictor of cardiac morbidity for
      aggressive radiotherapy. MATERIAL AND METHODS: The 23 patients received HT for
      the recurrent NSCLC at the bronchial stump site after right pneumonectomy between
      2008 and 2011. The median age of the patients was 65 years (range 56-74).
      RESULTS: We prescribed 95% volume of the primary planning target volume (PTV) to
      a total dose of 69 Gy in 30 fractions, and 95% of the secondary PTV to a total
      dose of 54 Gy in 30 fractions with reduction of the 50% volume of the heart < 20
      Gy. The median conformal index in the 23 plans was 1.21. The mean fraction of
      primary PTV receiving more than 95% of the prescribed dose was 97.8%. The mean
      V45, V50, V60 of the heart were 10.5%, 6.5%, 0.2%, respectively. The median
      follow-up after tomotherapy was 19.86 months. Median survival was 20 months. The
      2-year OS was 39.1%. CONCLUSIONS: The relatively high dose tomotherapy alone for
      patients with a recurrent bronchial stump mass which was proximal to the heart
      demonstrated favorable clinical results without severe heart or pulmonary
      complications.

PMID- 26199575
TI  - Analysis of the influence of parenteral cancer chemotherapy on the health
      condition of oral mucosa.
AB  - AIM OF THE STUDY: The present study was aimed at estimating the prevalence of
      oral complications in cancer patients receiving chemotherapy. MATERIAL AND
      METHODS: The study was conducted on a group of 58 patients treated with
      chemotherapy (study group). The control group consisted of 30 healthy patients.
      Dental status and oral mucosa were examined using the criteria of the National
      Cancer Institute Toxicity Criteria Scale. The levels of stimulated and
      unstimulated saliva flow were analysed. RESULTS: In the group of patients treated
      with chemotherapy, 59% of patients had inflammatory changes of the soft tissues
      of the mouth, such as erythema, erosions, or ulcers, which were discovered during
      dental examination. Such changes occurred in only 10% of patients in the control
      group. Six of the patients treated with chemotherapy reported pain with intensity
      was so severe that it caused swallowing difficulties. Patients in the study group
      frequently complained about the presence of dry mouth, taste disturbances,
      nausea, and vomiting. These symptoms occurred in 70% of patients undergoing
      oncological treatment. In both stimulated and unstimulated saliva secretion, the
      rates were significantly lower in patients from the research group, when compared
      to the control group.

PMID- 26199576
TI  - Sustained remission after ABVD treatment for interdigitating dendritic cell
      sarcoma.

PMID- 26199577
TI  - Evaluation of the Effect of Mega MSM on Improving Joint Function in Populations
      Experiencing Joint Degeneration.
AB  - Joint degeneration has become a commonplace problem in aging populations. The
      main clinical manifestations include joint pain, joint stiffness and joint
      swelling with functional disorder. Mega MSM is a nutritional supplement that may
      provide potential relief for joint problems associated with joint degeneration.
      The current experiment performed was a 12-week, randomized, double-blind,
      controlled study conducted on populations in China experiencing joint
      degeneration. The objective of the study was to determine whether the daily use
      of Mega MSM capsules could improve joint function, relieve symptoms of joint
      degeneration and improve the quality of life in aging populations. A total of 100
      male and female participants over 50 years old who had at least one of the
      related symptoms of joint degeneration (joint pain, joint stiffness, joint
      swelling, difficulty walking, difficulty getting up from bed and difficulty going
      down stairs) were recruited and their symptoms of joint degeneration before and
      after the intervention were recorded. In this study, Mega MSM shows positive
      effects in improving joint function, relieving symptoms associated with joint
      degeneration and improving the quality of life in aging populations. 

PMID- 26199578
TI  - Serosurvey of Entamoeba Histolytica Exposure among Tepehuanos Population in
      Durango, Mexico.
AB  - The seroepidemiology of Entamoeba histolytica infection in Tepehuanos population
      in Mexico is largely unknown. This study aimed to study the seroprevalence and
      correlates of E. histolytica antibodies in Tepehuanos in Durango, Mexico. Through
      a cross-sectional study, we determined the frequency of E. histolytica IgG
      antibodies in 156 Tepehuanos people in Durango, Mexico using an enzyme-linked
      immunoassay. Furthermore, we studied the association of E. histolytica
      seroprevalence with the socio-demographic, clinical, and behavioral
      characteristics of the Tepehuanos studied. Forty-four (28.2%) Tepehuanos with
      mean age of 31.03 +/- 16.71 years old had anti- E. histolytica IgG antibodies.
      Multivariate analysis showed that E. histolytica exposure was positively
      associated with laborer occupation (Odds ratio=2.77; 95% CI: 1.15, 6.66; p=0.02),
      and history of lymphadenopathy (Odds ratio=4.97; 95% CI: 1.74, 14.13; p=0.002),
      and negatively associated with soil contact (Odds ratio=0.13; 95% CI: 0.03, 0.53;
      p=0.004). Other behavioral characteristics including drinking untreated water or
      unpasteurized milk, and consumption of unwashed raw vegetables or fruits were not
      associated with E. histolytica exposure. The seroprevalence of E. histolytica
      infection in Tepehuanos in Durango is higher thanseroprevalences reported in
      national surveys. The factors associated with E. histolytica seropositivity
      reported in the present study might aid for the planning and implementation of
      effective measures against E. histolytica infection. 

PMID- 26199579
TI  - Purple Tea and Its Extract Suppress Diet-induced Fat Accumulation in Mice and
      Human Subjects by Inhibiting Fat Absorption and Enhancing Hepatic Carnitine
      Palmitoyltransferase Expression.
AB  - A number of clinical trials have been completed using green tea and black tea to
      investigate their effect in controlling weight in overweight adults. The results
      of these investigations, however, have often been contradictory, with some trials
      reporting positive effects of tea supplementation and some trials reporting no
      effect. As a result, the use of these teas for weight loss is controversial.
      Purple tea is a variety of green tea developed in Kenya (called TRFK306), which
      in addition to certain tea constituents found in green tea, also contains
      anthocyanins. The major constituents in the leaves of purple tea are caffeine,
      theobromine, epigallocatechin (ECG), epigallocatechin gallate (EGCG) and 1,2-di-O
      galloyl-4,6-O-(S)-hexahydroxydiphenoyl-beta-D-glucose (GHG). We investigated the
      efficacy of purple tea extract (PTE) on diet-induced fat accumulation in mice.
      PTE administration (200 mg/kg) significantly suppressed body weight gain, liver
      weight, abdominal fat and triglycerides in serum and liver. Protein expression of
      carnitine palmitoyltransferase (CPT) 1A was also enhanced. In olive oil loaded
      mice, PTE (100 mg/kg) and caffeine (25 mg/kg) suppressed fat absorption. PTE (10
      MUg/mL) and GHG (10 MUg/mL) also enhanced protein expression of CPT1A in HepG2
      hepatoma. Moreover, 4-week daily consumption of purple tea drink in humans
      improved obesity parameters compared to baseline, including body weight (79.9 +/-
      3.1 kg vs 80.8 +/- 3.2, p<0.05), body mass index (BMI) (26.8 +/- 0.6 vs 27.0 +/-
      0.6, p<0.05) and body fat mass (21.0 +/- 1.4 kg vs 21.8 +/- 1.5, p<0.01). In
      conclusion, PTE could control diet-induced weight gain by suppression of fat
      absorption and enhancement of hepatic fat metabolism. 

PMID- 26199580
TI  - A Preliminary Study of the Effects of SurAsleep on Relieving Symptoms of Sleep
      Disorders.
AB  - Sleep disorder is a common condition in the general population. Conventional
      sedative-hypnotic drug therapy may not be appropriate for many patients suffering
      from only mild-to-moderate sleep disorders. SurAsleep, a nutritional supplement
      that has been used by patients with sleep disorders in the United States, shows
      promising effects in improving sleep disorders and enhancing sleep quality.
      However, double-blinded, randomized and controlled studies have not been
      performed to determine the efficacy of the supplement. We conducted this study on
      individuals suffering from mild-to-moderate sleep disorders in Shanghai, China.
      In this study, we randomly assigned 100 participants over the age of 50 years old
      with symptoms of sleep disorders to a 12-week treatment with either SurAsleep or
      placebo. The results were measured by a self-administrated questionnaire on
      changes in symptoms, which covered 3 phases of sleep: the falling-asleep stage,
      the sleeping stage and the waking-up stage. We also measured the changes after
      the 12-week intervention using the Pittsburgh Sleep Quality Index (PSQI),
      including 7 dimensions of sleeping. All symptoms, dimension-specific PSQI scores
      and total PSQI scores showed significant improvement after using SurAsleep. In
      this study, SurAsleep has shown potent effects in relieving somnipathy-related
      symptoms and improving sleep quality in sleep disorder patients. 

PMID- 26199581
TI  - Effect of Age on Childbearing in Port Harcourt, Nigeria.
AB  - OBJECTIVES: To determine the effect of maternal age on pregnancy outcomes in
      women aged 40 years and above at the University of Port Harcourt Teaching
      Hospital. METHODS: A retrospective comparative study was conducted on women aged
      >=40 years (n=249) and a control group aged 20-29 years (n=249) who delivered at
      >=28 weeks gestation between January 1, 2008 and December 31, 2012. The medical
      records of the patients were analyzed using Epi Info 6.04d. Association between
      maternal age and selected obstetrical variables were assessed using the chi
      squared and the two-tailed Fisher exact test. Differences were considered
      statistically significant when p<=0.05. RESULTS: The mean age of the women in the
      study group was 41.2 +/-1.75 versus 26.10 +/- 2.37 in the control group. Advanced
      maternal age was associated with a significantly higher rate of hypertensive
      disorders of pregnancy (p=0.01), diabetes mellitus (p<0.01), abnormal
      lies/presentation (p=0.04), caesarean deliveries (p<0.01) and low birth weight
      (p=0.04). CONCLUSION: Older parturients have a higher risk of medical disorders
      of pregnancy. They are more likely to deliver by caesarean section and have low
      birth weight babies than their younger counterparts.

PMID- 26199582
TI  - African Nutmeg (Monodora Myristica) Lowers Cholesterol and Modulates Lipid
      Peroxidation in Experimentally Induced Hypercholesterolemic Male Wistar Rats.
AB  - To evaluate the cholesterol lowering potential and protective ability of aqueous
      extract of Monodora myristica experimental hypercholesterolemic rats, a short
      term study was conducted. Hypercholesterolemia was induced by administering
      cholesterol orally at a dose of 40 mg/kg/0.3 ml. Plant extracts 100 or 200 mg/kg
      body weight and Questran 0.26 g/kg were administered five times a week for eight
      weeks for amelioration. Hypolipidemic effects were evaluated by measuring total
      cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C) and triglycerides (TG) in the serum, while the
      protective ability was measured by the extent of lipid peroxidation (LPO) as well
      as enzymatic and non-enzymatic antioxidants levels in post mitochondrial
      fractions (PMF) of the hepatic and cardiac homogenates. Serum aminotransferases
      activities were also monitored. Results obtained shows that treatment with M.
      myristica elicited a significant reduction in serum TC, TG and LDL-C levels while
      there was concomitant increase in HDL-C of hypercholesterolemic rats. Elevations
      in serum aminotransferases activities and LPO level were reversed and a
      significant amelioration was noticed in enzymatic and non-enzymatic antioxidants
      status in the liver and heart of hypercholesterolemic rats. This study suggests
      that M. myristica possess cholesterol lowering potentials and protective ability
      in experimental hypercholesterolemia rat model. 

PMID- 26199583
TI  - Inequity in Timeliness of MMR Vaccination in Children Living in the Suburbs of
      Iranian Cities.
AB  - INTRODUCTION: High coverage of immunization is one of the indicators of good
      performance of health system but timely vaccination is another indicator which is
      associated with protective effect of vaccines. The present study aimed at
      evaluating the inequity in timely vaccination with a focus on inequities in
      timeliness by gender, birth order, parents' education and place of residence
      (rural or urban). METHODS: A historical cohort study was conducted on children of
      24-47 months of age who were living in the suburbs of big cities in Iran and were
      selected through stratified proportional sampling method. Only children who had
      vaccine cards -i.e. 3610 children -were included in data analysis. The primary
      outcome was age-appropriate vaccination of MMR1. Inequity was measured by
      Concentration Index (C) and Relative Index of Inequity (RII). Inequity indexes
      were calculated according to the mother and father's education, child birth
      order, child's sex and the family's place of residence at the time of
      vaccination. RESULTS: The overall on-time MMR1 vaccination was 70% and 54.4% for
      Iranians and Non-Iranians, respectively. The C index of mother and father's
      education for timely MMR vaccination was 0.023 and was 0.029 in Iranian children
      as well as 0.044 and 0.019 for non-Iranians, respectively. The C index according
      to child order in Iranians and Non-Iranians was 0.025 and C=0.078. With regard to
      children who lived in cities, the on-time vaccination was 0.36% and 0.29% higher
      than that in rural areas . In male children it was 0.12% and 0.14% higher than
      that in female children for Iranians and Non-Iranians, respectively. CONCLUSION:
      Timeliness MMR vaccination in Iranian children is higher than that in non-Iranian
      children. Regarding the existence of differences in timely vaccination rate in
      all Iranian and Non-Iranian children, no evidence was observed for inequity by
      focusing on parents' education, birth order, gender or place of residence. So,
      increasing timeliness of vaccination for enhancing the protective effect of
      vaccines can be considered a health-related goal in Iran after receiving high
      immunization coverage.

PMID- 26199584
TI  - To Evaluate & Compare Retention of Complete Cast Crown in Natural Teeth Using
      Different Auxiliary Retentive Features with Two Different Crown Heights - An In
      Vitro Study.
AB  - BACKGROUND & OBJECTIVES: To evaluate the retention of complete cast crowns in
      teeth with adequate and inadequate crown height and to evaluate the effects of
      auxiliary retentive features on retention form complete cast crowns. MATERIALS
      AND METHODS: Sixty freshly extracted human premolars. They were divided into 2
      major groups depending upon the height of the teeth after the preparation. Group1
      (H1): prepared teeth with constant height of 3.5 mm and Group 2 (H2): prepared
      teeth with constant height of 2.5 mm. Each group is further subdivided into 3
      subgroups, depending upon the retentive features incorporated. First sub group
      were prepared conventionally, second sub group with proximal grooves and third
      subgroups with proximal boxes preparation. Castings produced in Nickel chromium
      alloy were cemented with glass ionomer cement and the cemented castings were
      subjected to tensional forces required to dislodge each cemented casting from its
      preparation and used for comparison of retentive quality. The data obtained were
      statistically analyzed using Oneway ANOVA test. RESULTS: The results showed there
      was statistically significant difference between adequate (H1) and inadequate
      (H2) group and increase in retention when there was incorporation of retentive
      features compared to conventional preparations. Incorporation of retentive
      grooves was statistically significant compared to retention obtained by boxes.
      Results also showed there was no statistically significant difference between
      long conventional and short groove. CONCLUSION: Complete cast crowns on teeth
      with adequate crown height exhibited greater retention than with inadequate crown
      height. Proximal grooves provided greater amount of retention when compared with
      proximal boxes.

PMID- 26199585
TI  - Diagnosis of Second Mesiobuccal Canal in Maxillary First Molars among Patients
      Visiting a Tertiary Care Hospital.

PMID- 26199586
TI  - Synthesis, Characterization, and Anticancer Activity of New Metal Complexes
      Derived from 2-Hydroxy-3-(hydroxyimino)-4-oxopentan-2-ylidene)benzohydrazide.
AB  - Novel metal(II) complexes derived from 2-hydroxy-N'-((Z)-3-(hydroxyimino)-4
      oxopentan-2-ylidene)benzohydrazide ligand (H2L) were synthesized and
      characterized by elemental and thermal analyses (DTA and TGA), IR, UV-VIS, (1)H
      NMR, ESR and mass spectroscopy, magnetic susceptibilities, and conductivities
      measurements. The complexes adopt distorted octahedral geometry. The ESR spectra
      of the solid copper(II) complexes are characteristic to d(9) configuration and
      have an axial symmetry type of a d(x (2)-y (2)) ground state. The g values
      confirmed the tetragonal octahedral geometry with a considerably ionic or
      covalent environment. The cytotoxic activity of the ligand and its metal
      complexes showed potent cytotoxicity effect against growth of human liver cancer
      HepG2 cell lines compared to the clinically used Sorafenib (Nexavar). 

PMID- 26199587
TI  - Inhibition of kinesin-5 improves regeneration of injured axons by a novel
      microtubule-based mechanism.
AB  - Microtubules have been identified as a powerful target for augmenting
      regeneration of injured adult axons in the central nervous system. Drugs that
      stabilize microtubules have shown some promise, but there are concerns that
      abnormally stabilizing microtubules may have only limited benefits for
      regeneration, while at the same time may be detrimental to the normal work that
      microtubules perform for the axon. Kinesin-5 (also called kif11 or Eg5), a
      molecular motor protein best known for its crucial role in mitosis, acts as a
      brake on microtubule movements by other motor proteins in the axon. Drugs that
      inhibit kinesin-5, originally developed to treat cancer, result in greater
      mobility of microtubules in the axon and an overall shift in the forces on the
      microtubule array. As a result, the axon grows faster, retracts less, and more
      readily enters environments that are inhibitory to axonal regeneration. Thus,
      drugs that inhibit kinesin-5 offer a novel microtubule-based means to boost
      axonal regeneration without the concerns that accompany abnormal stabilization of
      the microtubule array. Even so, inhibiting kinesin-5 is not without its own
      caveats, such as potential problems with navigation of the regenerating axon to
      its target, as well as morphological effects on dendrites that could affect
      learning and memory if the drugs reach the brain. 

PMID- 26199589
TI  - Strategies to avoid a missed diagnosis of co-occurring concussion in post-acute
      patients having a spinal cord injury.
AB  - Research scientists and clinicians should be aware that missed diagnoses of mild
      moderate traumatic brain injuries in post-acute patients having spinal cord
      injuries may approach 60-74% with certain risk factors, potentially causing
      clinical consequences for patients, and confounding the results of clinical
      research studies. Factors leading to a missed diagnosis may include acute trauma
      related life-threatening issues, sedation/intubation, subtle neuropathology on
      neuroimaging, failure to collect Glasgow Coma Scale scores or duration of
      posttraumatic amnesia, or lack of validity of this information, and overlap in
      neuro-cognitive symptoms with emotional responses to spinal cord injuries.
      Strategies for avoiding a missed diagnosis of mild-moderate traumatic brain
      injuries in patients having a spinal cord injuries are highlighted in this
      perspective. 

PMID- 26199588
TI  - Mesenchymal stem cells-based therapy as a potential treatment in
      neurodegenerative disorders: is the escape from senescence an answer?
AB  - Aging is the most prominent risk factor contributing to the development of
      neurodegenerative disorders. In the United States, over 35 million of elderly
      people suffer from age-related diseases. Aging impairs the self-repair ability of
      neuronal cells, which undergo progressive deterioration. Once initiated, this
      process hampers the already limited regenerative power of the central nervous
      system, making the search for new therapeutic strategies particularly difficult
      in elderly affected patients. So far, mesenchymal stem cells have proven to be a
      viable option to ameliorate certain aspects of neurodegeneration, as they possess
      high proliferative rate and differentiate in vitro into multiple lineages.
      However, accumulating data have demonstrated that during long-term culture,
      mesenchymal stem cells undergo spontaneous transformation. Transformed
      mesenchymal stem cells show typical features of senescence, including the
      progressive shortening of telomers, which results in cell loss and, as a
      consequence, hampered regenerative potential. These evidences, in line with those
      observed in mesenchymal stem cells isolated from old donors, suggest that
      senescence may represent a limit to mesenchymal stem cells exploitation in
      therapy, prompting scholars to either find alternative sources of pluripotent
      cells or to arrest the age-related transformation. In the present review, we
      summarize findings from recent literature, and critically discuss some of the
      major hurdles encountered in the search of appropriate sources of mesenchymal
      stem cells, as well as benefits arising from their use in neurodegenerative
      diseases. Finally, we provide some insights that may aid in the development of
      strategies to arrest or, at least, delay the aging of mesenchymal stem cells to
      improve their therapeutic potential. 

PMID- 26199590
TI  - Phage display: development of nanocarriers for targeted drug delivery to the
      brain.
AB  - The blood brain barrier represents a formidable obstacle for the transport of
      most systematically administered neurodiagnostics and neurotherapeutics to the
      brain. Phage display is a high throughput screening strategy that can be used for
      the construction of nanomaterial peptide libraries. These libraries can be
      screened for finding brain targeting peptide ligands. Surface functionalization
      of a variety of nanocarriers with these brain homing peptides is a sophisticated
      way to develop nanobiotechnology-based drug delivery platforms that are able to
      cross the blood brain barrier. These efficient drug delivery systems raise our
      hopes for the diagnosis and treatment of various brain disorders in the future. 

PMID- 26199591
TI  - Matrilin-2, an extracellular adaptor protein, is needed for the regeneration of
      muscle, nerve and other tissues.
AB  - The extracellular matrix (ECM) performs essential functions in the
      differentiation, maintenance and remodeling of tissues during development and
      regeneration, and it undergoes dynamic changes during remodeling concomitant to
      alterations in the cell-ECM interactions. Here we discuss recent data addressing
      the critical role of the widely expressed ECM protein, matrilin-2 (Matn2) in the
      timely onset of differentiation and regeneration processes in myogenic, neural
      and other tissues and in tumorigenesis. As a multiadhesion adaptor protein, it
      interacts with other ECM proteins and integrins. Matn2 promotes neurite
      outgrowth, Schwann cell migration, neuromuscular junction formation, skeletal
      muscle and liver regeneration and skin wound healing. Matn2 deposition by
      myoblasts is crucial for the timely induction of the global switch toward
      terminal myogenic differentiation during muscle regeneration by affecting
      transforming growth factor beta/bone morphogenetic protein 7/Smad and other
      signal transduction pathways. Depending on the type of tissue and the
      pathomechanism, Matn2 can also promote or suppress tumor growth. 

PMID- 26199592
TI  - Protein deacetylases and axonal regeneration.

PMID- 26199593
TI  - From neurogenesis to neuronal regeneration: the amphibian olfactory system as a
      model to visualize neuronal development in vivo.

PMID- 26199594
TI  - Neuroprotective properties of kavalactones.

PMID- 26199595
TI  - Translocator protein 18 kDa (TSPO): old dogma, new mice, new structure, and new
      questions for neuroprotection.

PMID- 26199596
TI  - Mercury-induced neurotoxicity and neuroprotective effects of berberine.

PMID- 26199597
TI  - Receptor-mediated increase in rabies virus axonal transport.

PMID- 26199598
TI  - The kallikrein-kinin system: a promising therapeutic target for traumatic brain
      injury.

PMID- 26199599
TI  - Fine-tuning of cortical progenitor proliferation by thalamic afferents.

PMID- 26199600
TI  - Blood-brain barrier modeling: challenges and perspectives.

PMID- 26199601
TI  - Modification of autophagy-lysosomal pathway as a neuroprotective treatment for
      spinal cord injury.

PMID- 26199602
TI  - Cellular reprogramming and inherited peripheral neuropathies: perspectives and
      challenges.

PMID- 26199603
TI  - Laser capture microdissection: from its principle to applications in research on
      neurodegeneration.

PMID- 26199604
TI  - Onecut transcription factors in retinal development and maintenance.

PMID- 26199605
TI  - Is retinoic acid a signal for nerve regeneration in insects?

PMID- 26199606
TI  - 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal
      stem cell transplantation.
AB  - Cell therapy using stem cell transplantation against cerebral ischemia has been
      reported. However, it remains controversial regarding the optimal time for cell
      transplantation and the transplantation route. Rat models of cerebral ischemia
      were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1,
      3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were
      injected via the tail vein. At 28 days after cerebral ischemia, rat neurological
      function was evaluated using a 6-point grading scale and the pathological change
      of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the
      fluorescence microscope, the migration of bone marrow mesenchymal stem cells was
      examined by PKH labeling. Caspase-3 activity was measured using
      spectrophotometry. The optimal neurological function recovery, lowest degree of
      ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells
      migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic
      cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem
      cell transplantation at 12 hours after cerebral ischemia. These findings suggest
      that 12 hours after cerebral ischemia is the optimal time for tail vein injection
      of bone marrow mesenchymal stem cell transplantation against cerebral ischemia,
      and the strongest neuroprotective effect of this cell therapy appears at this
      time. 

PMID- 26199607
TI  - In vivo tracking of human adipose-derived stem cells labeled with ferumoxytol in
      rats with middle cerebral artery occlusion by magnetic resonance imaging.
AB  - Ferumoxytol, an iron replacement product, is a new type of superparamagnetic iron
      oxide approved by the US Food and Drug Administration. Herein, we assessed the
      feasibility of tracking transplanted human adipose-derived stem cells labeled
      with ferumoxytol in middle cerebral artery occlusion-injured rats by 3.0 T MRI in
      vivo. 1 * 10(4) human adipose-derived stem cells labeled with ferumoxytol-heparin
      protamine were transplanted into the brains of rats with middle cerebral artery
      occlusion. Neurologic impairment was scored at 1, 7, 14, and 28 days after
      transplantation. T2-weighted imaging and enhanced susceptibility-weighted
      angiography were used to observe transplanted cells. Results of imaging tests
      were compared with results of Prussian blue staining. The modified neurologic
      impairment scores were significantly lower in rats transplanted with cells at all
      time points except 1 day post-transplantation compared with rats without
      transplantation. Regions with hypointense signals on T2-weighted and enhanced
      susceptibility-weighted angiography images corresponded with areas stained by
      Prussian blue, suggesting the presence of superparamagnetic iron oxide particles
      within the engrafted cells. Enhanced susceptibility-weighted angiography image
      exhibited better sensitivity and contrast in tracing ferumoxytol-heparin
      protamine-labeled human adipose-derived stem cells compared with T2-weighted
      imaging in routine MRI. 

PMID- 26199608
TI  - Low-frequency transcranial magnetic stimulation is beneficial for enhancing
      synaptic plasticity in the aging brain.
AB  - In the aging brain, cognitive function gradually declines and causes a
      progressive reduction in the structural and functional plasticity of the
      hippocampus. Transcranial magnetic stimulation is an emerging and novel
      neurological and psychiatric tool used to investigate the neurobiology of
      cognitive function. Recent studies have demonstrated that low-frequency
      transcranial magnetic stimulation (<=1 Hz) ameliorates synaptic plasticity and
      spatial cognitive deficits in learning-impaired mice. However, the mechanisms by
      which this treatment improves these deficits during normal aging are still
      unknown. Therefore, the current study investigated the effects of transcranial
      magnetic stimulation on the brain-derived neurotrophic factor signal pathway,
      synaptic protein markers, and spatial memory behavior in the hippocampus of
      normal aged mice. The study also investigated the downstream regulator, Fyn
      kinase, and the downstream effectors, synaptophysin and growth-associated protein
      43 (both synaptic markers), to determine the possible mechanisms by which
      transcranial magnetic stimulation regulates cognitive capacity. Transcranial
      magnetic stimulation with low intensity (110% average resting motor threshold
      intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic
      factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice.
      The treatment also upregulated the mRNA and protein expression of synaptophysin
      and growth-associated protein 43 in the hippocampus of these mice. In conclusion,
      brain-derived neurotrophic factor signaling may play an important role in
      sustaining and regulating structural synaptic plasticity induced by transcranial
      magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical
      during this regulation. These responses may change the structural plasticity of
      the aging hippocampus, thereby improving cognitive function. 

PMID- 26199609
TI  - Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop.
AB  - Curcumin has been shown to significantly improve spatial memory impairment
      induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains
      unknown. Using extracellular microelectrode recording techniques, this study
      confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat
      hippocampal CA1 region and synaptic plasticity, and that curcumin could
      antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we
      found that curcumin resisted the effects of the gp120 V3 loop on hippocampal
      synaptosomes and decreased Ca(2+) concentration in synaptosomes. This effect of
      curcumin was identical to nimodipine, suggesting that curcumin improved the
      inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to
      the central nervous system, and might be a potential neuroprotective drug. 

PMID- 26199610
TI  - Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in
      rats.
AB  - The present study aimed to explore the mechanism underlying the protective
      effects of hydrogen sulfide against neuronal damage caused by cerebral
      ischemia/reperfusion. We established the middle cerebral artery occlusion model
      in rats via the suture method. Ten minutes after middle cerebral artery
      occlusion, the animals were intraperitoneally injected with hydrogen sulfide
      donor compound sodium hydrosulfide. Immunofluorescence revealed that the
      immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in
      rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide
      treatment. Furthermore, treatment of these rats with hydrogen sulfide
      significantly lowered mortality, the Longa neurological deficit scores, and
      infarct volume. These results indicate that hydrogen sulfide may be protective in
      rats with local cerebral ischemia/reperfusion injury by down-regulating the
      expression of P2X7 receptors. 

PMID- 26199611
TI  - Acrylamide neurotoxicity on the cerebrum of weaning rats.
AB  - The mechanism underlying acrylamide-induced neurotoxicity remains controversial.
      Previous studies have focused on acrylamide-induced toxicity in adult rodents,
      but neurotoxicity in weaning rats has not been investigated. To explore the
      neurotoxic effect of acrylamide on the developing brain, weaning rats were
      gavaged with 0, 5, 15, and 30 mg/kg acrylamide for 4 consecutive weeks. No
      obvious neurotoxicity was observed in weaning rats in the low-dose acrylamide
      group (5 mg/kg). However, rats from the moderate- and high-dose acrylamide groups
      (15 and 30 mg/kg) had an abnormal gait. Furthermore, biochemical tests in these
      rats demonstrated that glutamate concentration was significantly reduced, and
      gamma-aminobutyric acid content was significantly increased and was dependent on
      acrylamide dose. Immunohistochemical staining showed that in the cerebral cortex,
      gamma-aminobutyric acid, glutamic acid decarboxylase and glial fibrillary acidic
      protein expression increased remarkably in the moderate- and high-dose acrylamide
      groups. These results indicate that in weaning rats, acrylamide is positively
      associated with neurotoxicity in a dose-dependent manner, which may correlate
      with upregulation of gamma-aminobutyric acid and subsequent neuronal degeneration
      after the initial acrylamide exposure. 

PMID- 26199612
TI  - Delayed hippocampal neuronal death in young gerbil following transient global
      cerebral ischemia is related to higher and longer-term expression of p63 in the
      ischemic hippocampus.
AB  - The tumor suppressor p63 is one of p53 family members and plays a vital role as a
      regulator of neuronal apoptosis in the development of the nervous system.
      However, the role of p63 in mature neuronal death has not been addressed yet. In
      this study, we first compared ischemia-induced effects on p63 expression in the
      hippocampal regions (CA1-3) between the young and adult gerbils subjected to 5
      minutes of transient global cerebral ischemia. Neuronal death in the hippocampal
      CA1 region of young gerbils was significantly slow compared with that in the
      adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in
      the hippocampal CA1 pyramidal neurons in the sham-operated young group was
      significantly low compared with that in the sham-operated adult group. p63
      immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal
      neurons in both ischemia-operated young and adult groups. In the ischemia
      operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal
      neurons was significantly decreased at 4 days post-ischemia; however, p63
      immunoreactivity in the ischemia-operated young group was significantly higher
      than that in the ischemia-operated adult group. At 7 days post-ischemia, p63
      immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both
      ischemia-operated young and adult groups. Change patterns of p63 level in the
      hippocampal CA1 region of adult and young gerbils after ischemic damage were
      similar to those observed in the immunohistochemical results. These findings
      indicate that higher and longer-term expression of p63 in the hippocampal CA1
      region of the young gerbils after ischemia/reperfusion may be related to more
      delayed neuronal death compared to that in the adults. 

PMID- 26199613
TI  - Neuroprotective effect of rapamycin on spinal cord injury via activation of the
      Wnt/beta-catenin signaling pathway.
AB  - The Wnt/beta-catenin signaling pathway plays a crucial role in neural
      development, axonal guidance, neuropathic pain remission and neuronal survival.
      In this study, we initially examined the effect of rapamycin on the Wnt/beta
      catenin signaling pathway after spinal cord injury, by intraperitoneally
      injecting spinal cord injured rats with rapamycin over 2 days. Western blot
      analysis and immunofluorescence staining were used to detect the expression
      levels of beta-catenin protein, caspase-3 protein and brain-derived neurotrophic
      factor protein, components of the Wnt/beta-catenin signaling pathway. Rapamycin
      increased the levels of beta-catenin and brain-derived neurotrophic factor in the
      injured spinal cord, improved the pathological morphology at the injury site,
      reduced the loss of motor neurons, and promoted motor functional recovery in rats
      after spinal cord injury. Our experimental findings suggest that the
      neuroprotective effect of rapamycin intervention is mediated through activation
      of the Wnt/beta-catenin signaling pathway after spinal cord injury. 

PMID- 26199614
TI  - Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks
      promotes recovery after acute spinal cord injury.
AB  - Hydrogen can relieve tissue-damaging oxidative stress, inflammation and
      apoptosis. Injection of hydrogen-rich saline is an effective method for
      transporting molecular hydrogen. We hypothesized that hydrogen-rich saline would
      promote the repair of spinal cord injury induced by Allen's method in rats. At
      0.5, 1, 2, 4, 8, 12 and 24 hours after injury, then once daily for 2 weeks, 0.25
      mL/kg hydrogen-rich saline was infused into the subarachnoid space through a
      catheter. Results at 24 hours, 48 hours, 1 week and 2 weeks after injury showed
      that hydrogen-rich saline markedly reduced cell death, inflammatory cell
      infiltration, serum malondialdehyde content, and caspase-3 immunoreactivity,
      elevated serum superoxide dismutase activity and calcitonin gene-related peptide
      immunoreactivity, and improved motor function in the hindlimb. The present study
      confirms that hydrogen-rich saline injected within 2 weeks of injury effectively
      contributes to the repair of spinal cord injury in the acute stage. 

PMID- 26199615
TI  - Biological conduits combining bone marrow mesenchymal stem cells and
      extracellular matrix to treat long-segment sciatic nerve defects.
AB  - The transplantation of polylactic glycolic acid conduits combining bone marrow
      mesenchymal stem cells and extracellular matrix gel for the repair of sciatic
      nerve injury is effective in some respects, but few data comparing the
      biomechanical factors related to the sciatic nerve are available. In the present
      study, rabbit models of 10-mm sciatic nerve defects were prepared. The rabbit
      models were repaired with autologous nerve, a polylactic glycolic acid conduit +
      bone marrow mesenchymal stem cells, or a polylactic glycolic acid conduit + bone
      marrow mesenchymal stem cells + extracellular matrix gel. After 24 weeks,
      mechanical testing was performed to determine the stress relaxation and creep
      parameters. Following sciatic nerve injury, the magnitudes of the stress decrease
      and strain increase at 7,200 seconds were largest in the polylactic glycolic acid
      conduit + bone marrow mesenchymal stem cells + extracellular matrix gel group,
      followed by the polylactic glycolic acid conduit + bone marrow mesenchymal stem
      cells group, and then the autologous nerve group. Hematoxylin-eosin staining
      demonstrated that compared with the polylactic glycolic acid conduit + bone
      marrow mesenchymal stem cells group and the autologous nerve group, a more
      complete sciatic nerve regeneration was found, including good myelination,
      regularly arranged nerve fibers, and a completely degraded and resorbed conduit,
      in the polylactic glycolic acid conduit + bone marrow mesenchymal stem cells +
      extracellular matrix gel group. These results indicate that bridging 10-mm
      sciatic nerve defects with a polylactic glycolic acid conduit + bone marrow
      mesenchymal stem cells + extracellular matrix gel construct increases the stress
      relaxation under a constant strain, reducing anastomotic tension. Large
      elongations under a constant physiological load can limit the anastomotic opening
      and shift, which is beneficial for the regeneration and functional reconstruction
      of sciatic nerve. Better regeneration was found with the polylactic glycolic acid
      conduit + bone marrow mesenchymal stem cells + extracellular matrix gel grafts
      than with the polylactic glycolic acid conduit + bone marrow mesenchymal stem
      cells grafts and the autologous nerve grafts. 

PMID- 26199616
TI  - Sialic acid accelerates the electrophoretic velocity of injured dorsal root
      ganglion neurons.
AB  - Peripheral nerve injury has been shown to result in ectopic spontaneous
      discharges on soma and injured sites of sensory neurons, thereby inducing
      neuropathic pain. With the increase of membrane proteins on soma and injured site
      neurons, the negatively charged sialic acids bind to the external domains of
      membrane proteins, resulting in an increase of this charge. We therefore
      speculate that the electrophoretic velocity of injured neurons may be faster than
      non-injured neurons. The present study established rat models of neuropathic pain
      via chronic constriction injury. Results of the cell electrophoresis test
      revealed that the electrophoretic velocity of injured neuronal cells was faster
      than that of non-injured (control) cells. We then treated cells with divalent
      cations of Ca(2+) and organic compounds with positive charges, polylysine to
      counteract the negatively charged sialic acids, or neuraminidase to specifically
      remove sialic acids from the membrane surface of injured neurons. All three
      treatments significantly reduced the electrophoretic velocity of injured neuronal
      cells. These findings suggest that enhanced sialic acids on injured neurons may
      accelerate the electrophoretic velocity of injured neurons. 

PMID- 26199617
TI  - N-Propionylmannosamine stimulates axonal elongation in a murine model of sciatic
      nerve injury.
AB  - Increasing evidence indicates that sialic acid plays an important role during
      nerve regeneration. Sialic acids can be modified in vitro as well as in vivo
      using metabolic oligosaccharide engineering of the N-acyl side chain. N
      Propionylmannosamine (ManNProp) increases neurite outgrowth and accelerates the
      reestablishment of functional synapses in vitro. We investigated the influence of
      systemic ManNProp application using a specific in vivo mouse model. Using mice
      expressing axonal fluorescent proteins, we quantified the extension of
      regenerating axons, the number of regenerating axons, the number of arborising
      axons and the number of branches per axon 5 days after injury. Sciatic nerves
      from non-expressing mice were grafted into those expressing yellow fluorescent
      protein. We began a twice-daily intraperitoneal application of either
      peracetylated ManNProp (200 mg/kg) or saline solution 5 days before injury, and
      continued it until nerve harvest (5 days after transection). ManNProp
      significantly increased the mean distance of axonal regeneration (2.49 mm vs.
      1.53 mm; P < 0.005) and the number of arborizing axons (21% vs. 16%; P = 0.008) 5
      days after sciatic nerve grafting. ManNProp did not affect the number of
      regenerating axons or the number of branches per arborizing axon. The biochemical
      glycoengineering of the N-acyl side chain of sialic acid might be a promising
      approach for improving peripheral nerve regeneration. 

PMID- 26199618
TI  - Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve
      diseases: a preliminary report.
AB  - In this report, we present the results of a single patient with optic neuropathy
      treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an
      Institutional Review Board approved clinical trial and is the largest
      ophthalmology stem cell study registered at the National Institutes of Health to
      date- www.clinicaltrials.gov Identifier NCT 01920867. SCOTS utilizes autologous
      bone marrow-derived stem cells in the treatment of optic nerve and retinal
      diseases. Pre- and post-treatment comprehensive eye exams were independently
      performed at the Wilmer Eye Institute at the Johns Hopkins Hospital, USA. A 27
      year old female patient had lost vision approximately 5 years prior to enrollment
      in SCOTS. Pre-treatment best-corrected visual acuity at the Wilmer Eye Institute
      was 20/800 Right Eye (OD) and 20/4,000 Left Eye (OS). Four months following
      treatment in SCOTS, the central visual acuity had improved to 20/100 OD and 20/40
      OS. 

PMID- 26199619
TI  - Shrinkage of ipsilateral taste buds and hyperplasia of contralateral taste buds
      following chorda tympani nerve transection.
AB  - The morphological changes that occur in the taste buds after denervation are not
      well understood in rats, especially in the contralateral tongue epithelium. In
      this study, we investigated the time course of morphological changes in the taste
      buds following unilateral nerve transection. The role of the trigeminal component
      of the lingual nerve in maintaining the structural integrity of the taste buds
      was also examined. Twenty-four Sprague-Dawley rats were randomly divided into
      three groups: control, unilateral chorda tympani nerve transection and unilateral
      chorda tympani nerve transection + lingual nerve transection. Rats were allowed
      up to 42 days of recovery before being euthanized. The taste buds were visualized
      using a cytokeratin 8 antibody. Taste bud counts, volumes and taste receptor cell
      numbers were quantified and compared among groups. No significant difference was
      detected between the chorda tympani nerve transection and chorda tympani nerve
      transection + lingual nerve transection groups. Taste bud counts, volumes and
      taste receptor cell numbers on the ipsilateral side all decreased significantly
      compared with control. On the contralateral side, the number of taste buds
      remained unchanged over time, but they were larger, and taste receptor cells were
      more numerous postoperatively. There was no evidence for a role of the trigeminal
      branch of the lingual nerve in maintaining the structural integrity of the
      anterior taste buds. 

PMID- 26199620
TI  - Peripheral nerve repair: a hot spot analysis on treatment methods from 2010 to
      2014.
AB  - Therapeutic strategies for neurological deficits and for promoting nerve
      regeneration after peripheral nerve injuries have received much focus in clinical
      research. Advances in basic research in recent years have increased our
      understanding of the anatomy of peripheral nerves and the importance of the
      microenvironment. Various new intervention methods have been developed, but with
      varying effectiveness. In the present study, we selected 911 papers on different
      repair methods for peripheral nerve injury from the Web of Science and indexed in
      the Science Citation Index from 2010 to 2014. We quantitatively examine new
      repair methods and strategies using bibliometrics, and we discuss the present
      state of knowledge and the problems and prospects of various repair methods,
      including nerve transfer, neural transplantation, tissue engineering and genetic
      engineering. Our findings should help in the study and development of repair
      methods for peripheral nerve injury. 

PMID- 26199621
TI  - Nerve autografts and tissue-engineered materials for the repair of peripheral
      nerve injuries: a 5-year bibliometric analysis.
AB  - With advances in biomedical methods, tissue-engineered materials have developed
      rapidly as an alternative to nerve autografts for the repair of peripheral nerve
      injuries. However, the materials selected for use in the repair of peripheral
      nerve injuries, in particular multiple injuries and large-gap defects, must be
      chosen carefully. Various methods and materials for protecting the healthy tissue
      and repairing peripheral nerve injuries have been described, and each method or
      material has advantages and disadvantages. Recently, a large amount of research
      has been focused on tissue-engineered materials for the repair of peripheral
      nerve injuries. Using the keywords "pe-ripheral nerve injury", "autotransplant",
      "nerve graft", and "biomaterial", we retrieved publications using tissue
      engineered materials for the repair of peripheral nerve injuries appearing in the
      Web of Science from 2010 to 2014. The country with the most total publications
      was the USA. The institutions that were the most productive in this field include
      Hannover Medical School (Germany), Washington University (USA), and Nantong
      University (China). The total number of publications using tissue-engineered
      materials for the repair of peripheral nerve injuries grad-ually increased over
      time, as did the number of Chinese publications, suggesting that China has made
      many scientific contributions to this field of research. 

PMID- 26199622
TI  - Clutter Mitigation in Echocardiography Using Sparse Signal Separation.
AB  - In ultrasound imaging, clutter artifacts degrade images and may cause inaccurate
      diagnosis. In this paper, we apply a method called Morphological Component
      Analysis (MCA) for sparse signal separation with the objective of reducing such
      clutter artifacts. The MCA approach assumes that the two signals in the additive
      mix have each a sparse representation under some dictionary of atoms (a matrix),
      and separation is achieved by finding these sparse representations. In our work,
      an adaptive approach is used for learning the dictionary from the echo data. MCA
      is compared to Singular Value Filtering (SVF), a Principal Component Analysis-
      (PCA-) based filtering technique, and to a high-pass Finite Impulse Response
      (FIR) filter. Each filter is applied to a simulated hypoechoic lesion sequence,
      as well as experimental cardiac ultrasound data. MCA is demonstrated in both
      cases to outperform the FIR filter and obtain results comparable to the SVF
      method in terms of contrast-to-noise ratio (CNR). Furthermore, MCA shows a lower
      impact on tissue sections while removing the clutter artifacts. In experimental
      heart data, MCA obtains in our experiments clutter mitigation with an average CNR
      improvement of 1.33 dB. 

PMID- 26199623
TI  - Amrubicin Monotherapy for Patients with Platinum-Refractory
      Gastroenteropancreatic Neuroendocrine Carcinoma.
AB  - Objective. Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC)
      have a poor prognosis. Platinum-based combination chemotherapy is commonly used
      as first-line treatment; however, the role of salvage chemotherapy remains
      unknown. This study aimed to analyze the efficacy and safety of amrubicin
      monotherapy in patients with platinum-refractory gastroenteropancreatic NEC.
      Methods. Among 22 patients with advanced gastroenteropancreatic NEC, 10 received
      amrubicin monotherapy between September 2007 and May 2014 after failure of
      platinum-based chemotherapy. The efficacy and toxicity of the treatment were
      analyzed retrospectively. Results. Eight males and two females (median age, 67
      years (range, 52-78)) received platinum-based chemotherapy, including cisplatin
      plus irinotecan (n = 7, 70%), cisplatin plus etoposide (n = 2, 20%), and
      carboplatin plus etoposide (n = 1, 10%) before amrubicin therapy. Median
      progression-free survival and overall survival after amrubicin therapy were 2.6
      and 5.0 months, respectively. Two patients had partial response (20% response
      rate), and their PFS were 6.2 months and 6.3 months, respectively. Furthermore,
      NEC with response for amrubicin had characteristics with a high Ki-67 index and
      receipt of prior chemotherapy with cisplatin and irinotecan. Grade 3-4
      neutropenia and anemia were observed in four and five patients, respectively.
      Conclusion. Amrubicin monotherapy appears to be potentially active and well
      tolerated for platinum-refractory gastroenteropancreatic NEC. 

PMID- 26199625
TI  - Acute Renal Failure Induced by Chinese Herbal Medication in Nigeria.
AB  - Traditional herbal medicine is a global phenomenon especially in the resource
      poor economy where only the very rich can access orthodox care. These herbal
      products are associated with complications such as acute renal failure and liver
      damage with a high incidence of mortalities and morbidities. Acute renal failure
      from the use of herbal remedies is said to account for about 30-35% of all cases
      of acute renal failure in Africa. Most of the herbal medications are not usually
      identified, but some common preparation often used in Nigeria includes "holy
      water" green water leaves, bark of Mangifera indica (mango), shoot of Anacardium
      occidentale (cashew), Carica papaya (paw-paw) leaves, lime water, Solanum
      erianthum (Potato tree), and Azadirachta indica (Neem) trees. We report a rare
      case of a young man who developed acute renal failure two days after ingestion of
      Chinese herb for "body cleansing" and general wellbeing. He had 4 sessions of
      haemodialysis and recovered kidney function fully after 18 days of admission. 

PMID- 26199624
TI  - Optimal Endpoint of Therapy in IBD: An Update on Factors Determining a Successful
      Drug Withdrawal.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD) are chronic inflammatory
      disorders, which require long term treatment to achieve remission and to prevent
      relapses and cancer. While current therapies are effective in most cases, they
      can have rare but serious side effects and are often associated with high costs.
      On the other hand, early discontinuation of an effective treatment may lead to a
      quick relapse and to complications at the restart of therapy. Therefore it is
      essential to determine the optimal duration of maintenance therapy, but clear
      guidelines are missing. The most important questions when deciding whether to
      continue or withdraw therapy in quiescent UC and CD patients are the efficacy of
      the continuous treatment to maintain remission in the long term, the frequency
      and severity of side effects, and the chance of relapse after discontinuation of
      therapy. This review summarizes the current knowledge on these topics with
      respect to 5-aminosalicylates, thiopurines, methotrexate, and biological
      therapies and collects information regarding when and in which specific patient
      groups, in the absence of risk factors, can withdrawal of therapy be considered
      without a high risk of relapse. Additionally, the particular aspect of colorectal
      cancer prevention by current therapies will also be discussed. 

PMID- 26199626
TI  - Myocardial Infarction in a Premenopausal Woman on Leuprolide Therapy.
AB  - Premenopausal women with chest pain syndrome may have nonatherosclerotic coronary
      arteries with abnormal coronary flow. Estrogens have cardioprotective effect
      improving coronary vasodilatation. This case report discusses the consequences of
      leuprolide use by decreasing estrogen levels which led to acute myocardial
      infarction. 

PMID- 26199627
TI  - Hypercalcemia, Anemia, and Acute Kidney Injury: A Rare Presentation of
      Sarcoidosis.
AB  - We discuss a case of a 61-year-old woman who presented with substernal chest
      pain. She was found to have elevated calcium levels, anemia, and acute kidney
      injury. The hypercalcemia persisted despite therapy with fluids and
      bisphosphonates. She was found to have nonparathyroid hormone (PTH) mediated
      hypercalcemia. The chest X-ray did not reveal any pathology. Our Initial
      impression was likely underlying hematologic malignancy such as lymphoma or
      multiple myeloma. A bone marrow biopsy was performed that revealed nonnecrotizing
      granulomatous inflammation. Further workup revealed elevated vitamin 1,25
      dihydroxy level, beta-two microglobulin level, and ACE levels. Noncontrast
      computed tomography (CT) scan of chest showed bilateral apical bronchiectasis,
      but did not show any lymphadenopathy or evidence of malignancy. Subsequently, a
      fiber optic bronchoscopy with transbronchial biopsy showed nonnecrotizing
      granulomatous inflammation consistent with sarcoidosis. After initiating
      glucocorticoid therapy, the patient's hypercalcemia improved and her kidney
      function returned to baseline. 

PMID- 26199628
TI  - Bernese Periacetabular Osteotomy in a Hip Extra-Articular Resection Followed by
      Reconstruction Using an Extracorporeal Irradiated Acetabulum Autograft with
      Megaprosthesis, for Proximal Femur Osteosarcoma in a Pediatric Patient.
AB  - Osteosarcoma is the most common primary malignant tumour of bone. The oncologic
      surgery of a proximal femur osteosarcoma affecting the hip joint can be very
      challenging. We present an 8-year-old boy with a 5-month history of right hip
      pain. Radiographs and magnetic resonance imaging (MRI) showed a lytic lesion of
      the proximal femur extending 13 cm to the diaphysis. Histological evaluation was
      consistent with high-grade osteoblastic osteosarcoma. After completing
      chemotherapy we performed an extra-articular resection of the hip. Reconstruction
      was accomplished by reimplanting the acetabulum after irradiation and modular
      proximal femur megaprosthesis. Endoprosthetic reconstruction following proximal
      femur resection is a good treatment alternative achieving good postoperative
      function. Extra-articular resection of the hip using a periacetabular osteotomy
      technique enabled us to achieve wide margins and leave an intact posterior column
      to optimize acetabular reconstruction stability. Extracorporeal irradiation and
      reimplantation is a valuable treatment option in a situation such as this where
      allograft geometric fit is a priority. We conclude that an extra-articular
      resection of the hip, followed by reconstruction with an extracorporeally
      irradiated acetabulum and a proximal femur modular megaprosthesis, is a useful
      combined treatment option for malignant lesions involving the hip joint,
      especially in paediatric patients. 

PMID- 26199630
TI  - Evaluation of Antidiabetic Effects of the Traditional Medicinal Plant Gynostemma
      pentaphyllum and the Possible Mechanisms of Insulin Release.
AB  - Aims. To evaluate the antidiabetic effects of Gynostemma pentaphyllum (GP) in
      Goto-Kakizaki (GK) rat, an animal model of type 2 diabetes, and to investigate
      the mechanisms of insulin release. Methods. Oral glucose tolerance test was
      performed and plasma insulin levels were measured. Results. An oral treatment
      with GP (0.3 g/kg of body weight daily) for two weeks in GK rats improved glucose
      tolerance versus placebo group (P < 0.01). Plasma insulin levels were
      significantly increased in the GP-treated group. The insulin release from GP
      treated GK rats was 1.9-fold higher as compared to the control group (P < 0.001).
      GP stimulated insulin release in isolated GK rat islets at high glucose. Opening
      of ATP-sensitive potassium (K-ATP) channels by diazoxide and inhibition of
      calcium channels by nifedipine significantly decreased insulin response to GP.
      Furthermore, the protein kinase A (PKA) inhibitor H89 decreased the insulin
      response to GP (P < 0.05). In addition, GP-induced insulin secretion was
      decreased after preincubation of GK islets with pertussis toxin to inhibit
      exocytotic Ge proteins (P < 0.05). Conclusion. The antidiabetic effect of GP is
      associated with the stimulation of insulin release from the islets. GP-induced
      insulin release is partly mediated via K-ATP and L-type Ca(2+) channels, the PKA
      system and also dependent on pertussis toxin sensitive Ge-protein. 

PMID- 26199631
TI  - The Determinants of Choosing Traditional Korean Medicine or Conventional
      Medicine: Findings from the Korea Health Panel.
AB  - The purpose of this study is to identify key factors that determine a person's
      decision to seek treatment from traditional Korean medicine (TKM) instead of
      conventional medicine through analysis of nationally representative data from
      Korea, where a dual healthcare system exists. The analysis is based on episodic
      data from the 2008 and 2009 Korea Health Panel. The main dependent variable is
      the selection between TKM and conventional medicine. We used a multiple logistic
      regression model to identify the determinants of TKM while controlling for
      clustered error. Approximately 5% of all doctor's visits were characterized as
      TKM services. Urban residents were 1.441 times more likely to use TKM than rural
      residents (P = 0.001). The probability of choosing TKM over conventional medicine
      for a range of conditions compared to the reference condition (gastrointestinal
      disease) was as follows: circulatory system diseases (OR 5.267, P < 0.001),
      nervous system diseases (OR 12.054, P < 0.001), musculoskeletal system diseases
      (OR 20.579, P < 0.001), and neoplasms (OR 0.209, P = 0.004). Certain diseases are
      significantly more likely to be treated by TKM than by conventional medicine.
      This suggests that many people view TKM as being additionally effective for
      specific diseases, particularly musculoskeletal disorders. 

PMID- 26199629
TI  - Advances and Prospects in Tissue-Engineered Meniscal Scaffolds for Meniscus
      Regeneration.
AB  - The meniscus plays a crucial role in maintaining knee joint homoeostasis.
      Meniscal lesions are relatively common in the knee joint and are typically
      categorized into various types. However, it is difficult for inner avascular
      meniscal lesions to self-heal. Untreated meniscal lesions lead to meniscal
      extrusions in the long-term and gradually trigger the development of knee
      osteoarthritis (OA). The relationship between meniscal lesions and knee OA is
      complex. Partial meniscectomy, which is the primary method to treat a meniscal
      injury, only relieves short-term pain; however, it does not prevent the
      development of knee OA. Similarly, other current therapeutic strategies have
      intrinsic limitations in clinical practice. Tissue engineering technology will
      probably address this challenge by reconstructing a meniscus possessing an
      integrated configuration with competent biomechanical capacity. This review
      describes normal structure and biomechanical characteristics of the meniscus,
      discusses the relationship between meniscal lesions and knee OA, and summarizes
      the classifications and corresponding treatment strategies for meniscal lesions
      to understand meniscal regeneration from physiological and pathological
      perspectives. Last, we present current advances in meniscal scaffolds and provide
      a number of prospects that will potentially benefit the development of meniscal
      regeneration methods. 

PMID- 26199632
TI  - Effects of the Fourth Ventricle Compression in the Regulation of the Autonomic
      Nervous System: A Randomized Control Trial.
AB  - Introduction. Dysfunction of the autonomic nervous system is an important factor
      in the development of chronic pain. Fourth ventricle compression (CV-4) has been
      shown to influence autonomic activity. Nevertheless, the physiological mechanisms
      behind these effects remain unclear. Objectives. This study is aimed at
      evaluating the effects of fourth ventricle compression on the autonomic nervous
      system. Methods. Forty healthy adults were randomly assigned to an intervention
      group, on whom CV-4 was performed, or to a control group, who received a placebo
      intervention (nontherapeutic touch on the occipital bone). In both groups,
      plasmatic catecholamine levels, blood pressure, and heart rate were measured
      before and immediately after the intervention. Results. No effects related to the
      intervention were found. Although a reduction of norepinephrine, systolic blood
      pressure, and heart rate was found after the intervention, it was not exclusive
      to the intervention group. In fact, only the control group showed an increment of
      dopamine levels after intervention. Conclusion. Fourth ventricle compression
      seems not to have any effect in plasmatic catecholamine levels, blood pressure,
      or heart rate. Further studies are needed to clarify the CV-4 physiologic
      mechanisms and clinical efficacy in autonomic regulation and pain treatment. 

PMID- 26199633
TI  - Tissue Pharmacology of Da-Cheng-Qi Decoction in Experimental Acute Pancreatitis
      in Rats.
AB  - Objectives. The Chinese herbal medicine Da-Cheng-Qi Decoction (DCQD) can
      ameliorate the severity of acute pancreatitis (AP). However, the potential
      pharmacological mechanism remains unclear. This study explored the potential
      effective components and the pharmacokinetic characteristics of DCQD in target
      tissue in experimental acute pancreatitis in rats. Methods. Acute pancreatitis
      like symptoms were first induced in rats and then they were given different doses
      of DCQD (6 g/kg, 12 g/kg, and 24 g/kg body weight) orally. Tissue drug
      concentration, tissue pathological score, and inflammatory mediators in pancreas,
      intestine, and lung tissues of rats were examined after 24 hours, respectively.
      Results. Major components of DCQD could be found in target tissues and their
      concentrations increased in conjunction with the intake dose of DCQD. The high
      dose compounds showed maximal effect on altering levels of anti-inflammatory
      (interleukin-4 and interleukin-10) and proinflammatory markers (tumor necrosis
      factor alpha and interleukin-6) and ameliorating the pathological damage in
      target tissues (P < 0.05). Conclusions. DCQD could alleviate pancreatic,
      intestinal, and lung injury by altering levels of inflammatory cytokines in AP
      rats with tissue distribution of its components. 

PMID- 26199634
TI  - Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal
      Mucosal Injury in Animal Models.
AB  - The present study aimed to investigate the effects of oral administration of
      escin on acute inflammation and intestinal mucosal injury in animal models. The
      effects of escin on carrageenan-induced paw edema in a rat model of acute
      inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury
      in a mouse model, were observed. It was shown that oral administration of escin
      inhibits carrageenan-induced paw edema and decreases the production of
      prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of
      escin ameliorates endotoxin induced liver injury and intestinal mucosal injury
      and increases the expression of tight junction protein claudin-5 in mice. These
      findings suggest that escin effectively inhibits acute inflammation and reduces
      intestinal mucosal injury in animal models. 

PMID- 26199635
TI  - Perspectives on the Market Globalization of Korean Herbal Manufacturers: A
      Company-Based Survey.
AB  - The growth of herbal markets has increased substantially in South Korea, but the
      worldwide market share remains small despite significant governmental efforts.
      This study aimed to characterize manufacturing employment and identify employees'
      general perceptions of market expansion. A survey study covering 567 companies
      was conducted using face-to-face interviews in 2012. Data were analyzed using
      comparisons among three manufacturing groups (i.e., the herbal dietary supplement
      manufacturing group, the herbal medicine manufacturing group, and the personal
      care product manufacturing group) or among the manufacturers themselves. We found
      that the majority of the manufacturing employee respondents were regular
      permanent and production workers. The domestic distributors were primarily chain
      stores/direct outlets or retailers/wholesalers, and the dominant product was red
      ginseng (hongsam). Although the responding companies exhibited a variety of
      perspectives, "advertisement/public relations" was cited as the most important
      factor in the development of the herbal industry. In contrast, "low
      manpower/seeking business partners" were the most crucial limiting and
      challenging factors for market globalization. Our results can be used to design a
      proper national plan by reducing the gaps in perspective between herbal product
      producers and policy makers. 

PMID- 26199636
TI  - Liquiritigenin Protects Rats from Carbon Tetrachloride Induced Hepatic Injury
      through PGC-1alpha Pathway.
AB  - The lack of effective treatment for liver cirrhosis and hepatocellular carcinomas
      imposes serious challenges to the healthcare system. Here, we investigated the
      efficacy and mechanism of liquiritigenin involved in preventing or retarding the
      progression of liver diseases in a rat model with chronic carbon tetrachloride
      (CCl4) exposure. Sprague Dawley rats were given CCl4 and lliquiritigenin alone or
      simultaneously for 8 weeks before liver was harvested to check histological
      changes by Hematoxylin and Eosin (H&E) staining, apoptosis by TUNEL assay, ROS by
      dihydroethidium staining, antioxidant enzyme activities and malondialdehyde using
      specific kits, and gene expression by quantitative real-time PCR and western
      blot. Chronic CCl4 exposure caused profound changes in liver histology with
      extensive hepatocyte death (necrosis and apoptosis), fat accumulation, and
      infiltration of inflammatory cells, accompanied by depressed activities of
      antioxidant enzymes, increased oxidative stress, elevated expression of
      inflammation and fibrotic genes, and downregulation of PGC-1alpha, ND1, and Bcl-x
      in rat liver. All these changes were abolished or alleviated by lliquiritigenin.
      The results demonstrated that liquiritigenin is effective in protecting liver
      from injury or treating chronic liver diseases. The modulation of PGC-1alpha and
      its downstream genes might play a critical role in relieving CCl4-induced hepatic
      pathogenesis by liquiritigenin. 

PMID- 26199637
TI  - Effect of Luteolin on 11Beta-Hydroxysteroid Dehydrogenase in Rat Liver and
      Kidney.
AB  - 11Beta-hydroxysteroid dehydrogenase (11beta-HSD) enzymes control the
      glucocorticoid (GC) signaling, which is essential in regulating homeostasis. Our
      previous study revealed that Eclipta prostrata (EP) affected the activity and
      expression of 11beta-HSD enzymes which might improve the efficacy and reduce the
      adverse drug effects of glucocorticoid in patients undergoing combinational
      therapy. However, it is still unclear which composition of EP plays a major role
      and how it works. In this paper, we chose Luteolin which is one of the main
      ingredients of EP and evaluated its effect and metabolism in combination with
      prednisone. The effects of different concentrations of Luteolin extract on
      prednisone/prednisolone metabolism indicated the enzyme activity of 11beta-HSD,
      so the production rate (pmol/min per mg protein) of metabolites was used to
      indicate enzyme activity. Furthermore, we explored the influence of Luteolin on
      gene and protein expressions of 11beta-HSD I/II in rat liver and kidney tissue.
      Our results showed that oral administration of Luteolin significantly increased
      the gene and protein expressions of hepatic 11beta-HSD I and renal 11beta-HSD II,
      which may improve the efficacy and reduce the adverse drug effect of
      glucocorticoid in clinical application. A potential clinical value of Luteolin
      would also be indicated in combination therapy with prednisone for the treatment
      of nephrotic syndrome. 

PMID- 26199638
TI  - Clinical Effect of Shenfu Injection in Patients with Septic Shock: A Meta
      Analysis and Systematic Review.
AB  - Purpose. To conduct a meta-analysis evaluating the efficacy of Shenfu injection
      for treating patients with septic shock when compared with conventional therapy.
      Methods. Eight databases including Pubmed, EMBASE, Cochrane Library, ISI Web of
      Science, CNKI, Wanfang, VIP, and CBM were searched up to October 2014. Randomized
      controlled trials assessing the efficacy of Shenfu injection were identified.
      Mean arterial pressure, heart rate, lactate, and mortality were included as
      outcome measurements. Results. We analyzed data from 12 randomized controlled
      trials involving 904 participants. Compared with conventional therapy, Shenfu
      injection could further increase the mean arterial pressure at 1 hour (SMD 0.38;
      95% CI, 0.01-0.74) and 6 hours (SMD 0.82; 95% CI, 0.03-1.61). Shenfu injection
      could further normalize heart rate at 6 hours (SMD -0.90; 95% CI, -1.47-0.33) and
      clear serum lactate at 6 hours (SMD -0.51; 95% CI, -0.70-0.32) and 24 hours (SMD,
      0.52; 95% CI, -0.77-0.26). As the endpoint of mortality was not unified, it was
      not meta-analyzed. Conclusions. Based on the findings in present review, Shenfu
      injection is more effective than conventional therapy in increasing mean arterial
      pressure, normalizing heart rate, clearing serum lactate, and reducing mortality.
      These results should be confirmed in higher level clinical trials in the future. 

PMID- 26199639
TI  - Bavachalcone Enhances RORalpha Expression, Controls Bmal1 Circadian
      Transcription, and Depresses Cellular Senescence in Human Endothelial Cells.
AB  - The circadian clock regulates many aspects of (patho)physiology in the central
      nervous system and in the peripheral tissues. RAR-related orphan receptor alpha
      (RORalpha), an orphan nuclear receptor, is involved in circadian rhythm
      regulation, including regulation of cardiovascular function. Bavachalcone, a
      prenylchalcone, is a major bioactive chalcone isolated from Psoralea corylifolia.
      This natural ingredient activated RORalpha1 luciferase reporter activity on drug
      screening. In addition, bavachalcone induced RORalpha1 expression in mRNA and
      protein levels in a dose-dependent manner and enhanced the circadian amplitude of
      Bmal1 mRNA expression after serum shock. Moreover, bavachalcone suppressed
      senescence in human endothelial cells and mRNA expression of p16(ink4a) (a marker
      of replicative senescence) and IL-1alpha (a proinflammatory cytokine of the
      senescence-associated secretory phenotype). These inhibitory effects were
      partially reversed by the RORalpha inhibitor VPR-66. Our results demonstrate that
      bavachalcone, as a natural medicine ingredient, has a pharmacological function in
      regulating RORalpha1. 

PMID- 26199640
TI  - The global variability of diatomaceous earth toxicity: a physicochemical and in
      vitro investigation.
AB  - BACKGROUND: Diatomaceous earth (DE) is mined globally and is potentially of
      occupational respiratory health concern due to the high crystalline silica
      content in processed material. DE toxicity, in terms of variability related to
      global source and processing technique, is poorly understood. This study
      addresses this variability using physicochemical characterisation and in vitro
      toxicology assays. METHODS: Nineteen DE samples sourced from around the world,
      comprising unprocessed, calcined and flux-calcined DE, were analysed for chemical
      and mineral composition, particle size and morphology, and surface area. The
      potential toxicity of DE was assessed by its haemolytic capacity, and its ability
      to induce cytotoxicity or cytokine release by J774 macrophages. RESULTS: The
      potential toxicity of DE varied with source and processing technique, ranging
      from non-reactive to as cytotoxic and haemolytic as DQ12. Crystalline silica
      rich, flux-calcined samples were all unreactive, regardless of source. The
      potential toxicity of unprocessed and calcined samples was variable, and did not
      correlate with crystalline silica content. Calcium-rich phases, iron content,
      amorphous material, particle size and morphology all appeared to play a role in
      sample reactivity. An increased surface area was linked to an increased
      reactivity in vitro for some sample types. CONCLUSIONS: Overall, no single
      property of DE could be linked to its potential toxicity, but crystalline silica
      content was not a dominant factor. Occlusion of the potentially toxic crystalline
      silica surface by an amorphous matrix or other minerals and impurities in the
      crystal structure are suggested to pacify toxicity in these samples. In vivo
      verification is required, but these data suggest that crystalline silica content
      alone is not a sufficient indicator of the potential DE hazard.

PMID- 26199641
TI  - Undersampled MR Image Reconstruction with Data-Driven Tight Frame.
AB  - Undersampled magnetic resonance image reconstruction employing sparsity
      regularization has fascinated many researchers in recent years under the support
      of compressed sensing theory. Nevertheless, most existing sparsity-regularized
      reconstruction methods either lack adaptability to capture the structure
      information or suffer from high computational load. With the aim of further
      improving image reconstruction accuracy without introducing too much computation,
      this paper proposes a data-driven tight frame magnetic image reconstruction (DDTF
      MRI) method. By taking advantage of the efficiency and effectiveness of data
      driven tight frame, DDTF-MRI trains an adaptive tight frame to sparsify the to-be
      reconstructed MR image. Furthermore, a two-level Bregman iteration algorithm has
      been developed to solve the proposed model. The proposed method has been compared
      to two state-of-the-art methods on four datasets and encouraging performances
      have been achieved by DDTF-MRI. 

PMID- 26199642
TI  - Integrating staff well-being into the Primary Health Care system: a case study in
      post-conflict Kosovo.
AB  - BACKGROUND: Staff well-being including stress awareness and stress management
      skills is usually not a priority in (mental) health policies. In Kosovo, the
      level of stress amongst primary health care (PHC) professionals is high because
      health professionals are part of the population seriously affected by conflict.
      The need to support staff and look after their well-being was recognised by the
      Director of the Centre for Development of Family Medicine, Head of Primary Care.
      In response, the Antares Foundation and the Kosovo Rehabilitation Centre for
      Torture Victims (KRCT), in close cooperation with the Centers for Disease Control
      and Prevention, implemented an integrated psycho-social capacity building
      programme for PHC professionals. CASE-DESCRIPTION: This case-study describes how
      staff well-being was integrated into the PHC system in Kosovo. This was
      accomplished through raising awareness on staff well-being and stress management
      as well as strengthening knowledge of and skills in stress management. Eighteen
      national PHC staff were trained and more than a thousand family doctors and
      nurses attended stress management workshops. A steering committee consisting of
      key stakeholders was responsible for overseeing the execution of the programme.
      This steering committee successfully advocated for integration of staff well
      being and stress management in the revised mental health strategy 2014-2020. The
      curriculum developed for the training was integrated in the professional staff
      development programme for family doctors and nurses. The effectiveness of the
      programme was assessed through an evaluation (including a survey among PHC
      professionals trained under the programme). CONCLUSIONS: Evaluation findings
      showed that offering structured support, entailing the opportunity to discuss
      work related problems and providing tools to deal with stress related to work or
      personal life, helps staff to continue their professional tasks under challenging
      conditions. Evaluation findings suggest that results can be sustained through an
      integrated approach and involvement of key stakeholders. The case study may be of
      interest to policy makers involved in health reform processes and for managers
      implementing changes in complicated post conflict contexts. For both groups,
      acknowledgment of staff well-being could be a key ingredient in the motivation of
      staff and the quality of services.

PMID- 26199643
TI  - Localization of polyhydroxybutyrate in sugarcane using Fourier-transform infrared
      microspectroscopy and multivariate imaging.
AB  - BACKGROUND: Slow-degrading, fossil fuel-derived plastics can have deleterious
      effects on the environment, especially marine ecosystems. The production of bio
      based, biodegradable plastics from or in plants can assist in supplanting those
      manufactured using fossil fuels. Polyhydroxybutyrate (PHB) is one such
      biodegradable polyester that has been evaluated as a possible candidate for
      relinquishing the use of environmentally harmful plastics. RESULTS: PHB,
      possessing similar properties to polyesters produced from non-renewable sources,
      has been previously engineered in sugarcane, thereby creating a high-value co
      product in addition to the high biomass yield. This manuscript illustrates the
      coupling of a Fourier-transform infrared microspectrometer, equipped with a focal
      plane array (FPA) detector, with multivariate imaging to successfully identify
      and localize PHB aggregates. Principal component analysis imaging facilitated the
      mining of the abundant quantity of spectral data acquired using the FPA for
      distinct PHB vibrational modes. PHB was measured in the chloroplasts of mesophyll
      and bundle sheath cells, acquiescent with previously evaluated plant samples.
      CONCLUSION: This study demonstrates the power of IR microspectroscopy to rapidly
      image plant sections to provide a snapshot of the chemical composition of the
      cell. While PHB was localized in sugarcane, this method is readily transferable
      to other value-added co-products in different plants.

PMID- 26199644
TI  - Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer
      Agent.
AB  - We reported earlier the diagnostic potential of a melanogenic vaccinia virus
      based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging
      (MSOT). Since melanin overproduction lead to attenuated virus replication, we
      constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which
      expressed the key enzyme of melanogenesis (tyrosinase) under the control of an
      inducible promoter-system. In this study melanin production was detected after
      exogenous addition of doxycycline in two different tumor xenograft mouse models.
      Furthermore, it was confirmed that this novel vaccinia virus strain still
      facilitated signal enhancement as detected by MRI and optoacoustic tomography. At
      the same time we demonstrated an enhanced oncolytic potential compared to the
      constitutively melanin synthesizing rVACV system. 

PMID- 26199645
TI  - Enzyme-Controlled Intracellular Self-Assembly of (18)F Nanoparticles for Enhanced
      MicroPET Imaging of Tumor.
AB  - Herein, we report the development of a new "smart" radioactive probe (i.e., 1)
      which can undergo furin-controlled condensation and self-assembly of radioactive
      nanoparticles (i.e., 1-NPs) in tumor cells and its application for enhanced
      microPET imaging of tumors in nude mice co-injected with its cold analog (i.e., 1
      Cold). Furin-controlled condensation of 1-Cold and self-assembly of its
      nanoparticles (i.e., 1-Cold-NPs) in vitro were validated and characterized with
      HPLC, mass spectra, SEM, and TEM analyses. Cell uptake studies showed that both 1
      and 1-Cold have good cell permeability. TEM images of 1-Cold-treated MDA-MB-468
      cells directly uncovered that the intracellular 1-Cold-NPs were at/near the
      location of furin (i.e., Golgi bodies). MTT results indicated that 50 uM 1-Cold
      did not impose cytotoxicity to MDA-MB-468 cells up to 12 hours. MicroPET imaging
      of MDA-MB-468 tumor-bearing mice indicated that mice co-injected with 1 and 1
      Cold showed higher uptake and longer attenuation of the radioactivity in tumors
      than those mice only injected with same dosage of 1. Tumor uptake ratios of 1
      between these two groups of mice reached the maximum of 8.2 folds at 240 min post
      injection. Biodistribution study indicated that the uptake ratios of 1 in kidneys
      between these two groups continuously increased and reached 81.9 folds at 240 min
      post injection, suggesting the formation of radioactive NPs (i.e., 1-NPs) in MDA
      MB-468 tumors of mice co-injected with 1 and 1-Cold. And the nanoparticles were
      slowly digested and secreted from the tumors, accumulating in the kidneys. Our
      ''smart'' probe (i.e., 1), together with the strategy of co-injection, might help
      researchers trace the biomarkers of interest within a longer time window. 

PMID- 26199646
TI  - Photoluminescent Mesoporous Silicon Nanoparticles with siCCR2 Improve the Effects
      of Mesenchymal Stromal Cell Transplantation after Acute Myocardial Infarction.
AB  - BACKGROUND: Despite the benefits of mesenchymal stromal cell (MSC)
      transplantation in cardiac tissue, detailed in vivo observations have shown that
      MSCs only survive for a brief period after transplantation due to harsh
      microenvironmental conditions, including ischemia, inflammation and anoikis, in
      the infarcted myocardium. Thus, new strategies are needed to enhance MSC survival
      and inhibit cardiac remodeling. Studies have now demonstrated that chemokine [C-C
      motif] ligand 2 (CCL2) and its cognate receptor C-C chemokine receptor 2 (CCR2)
      promote excessive Ly6C(high) inflammatory monocyte infiltration at the infarct in
      response to ischemic myocardial injury. Therefore, decreasing the activities of
      these monocytes immediately after acute myocardial infarction (AMI) could be
      beneficial for AMI patients. OBJECTIVES: This study tested the hypothesis that
      therapeutic siRNA-loaded photoluminescent mesoporous silicon nanoparticles
      (PMSNs) targeting CCR2 expression in Ly6C(high) inflammatory monocytes decrease
      the accumulation of these cells in the infarct, improve the efficacy of MSC
      transplantation and attenuate myocardial remodeling. METHODS: PMSNs carrying
      therapeutic siCCR2 were first synthesized without the inclusion of fluorescent
      materials or dyes. After AMI BALB/c mice were established, 10(5) 5-ethynyl-2'-
      deoxyuridine (EdU)-labeled MSCs suspended in 100 ul of phosphate buffered saline
      (PBS) were injected into the border zone of the infarct of each mouse. PMSNs
      siCCR2 (25 ug/g) were also intravenously injected via the tail vein immediately
      following AMI induction. Control mice were injected with an equal amount of PMSNs
      without siCCR2. PMSNs-siCCR2 were examined in vivo using near-infrared imaging
      technology. The therapeutic effects of PMSNs-siCCR2 for MSC transplantation were
      determined at the mRNA, protein and functional levels. RESULTS: PMSNs-siCCR2
      circulated freely in vivo and were cleared in a relatively short period of time
      (t(1/2)=37 min) with no evidence of toxicity. The therapeutic PMSNs-siCCR2 showed
      higher levels of cellular accumulation in Ly6C(high) monocytes in the spleen and
      more efficient degradation of CCR2 compared with the control (8.04%+/-2.17% vs.
      20.02%+/-4.55%, p<0.001). Subsequently, the PMSNs-siCCR2 decreased the
      accumulation of CD11b-positive monocytes at the infarct (49.3%+/-17.34% vs.
      61.32%+/-22.43%, p<0.001) on day 1. Increased survival of transplanted MSCs (13+/
      3/mm(2) vs. 4+/-1/mm(2), p<0.001) and significantly decreased TdT-mediated dUTP
      nick end labeling (TUNEL)(+) cardiac myocytes (17.44%+/-6.26% vs. 39.49%+/
      13.28%, p<0.001) were then identified in the infarct zone three days after AMI
      induction in the PMSNs-siCCR2 group. Three weeks after MSC injection, significant
      increases were observed in the vascular density (235.5+/-39.6/mm(2) vs. 147.4+/
      20.3/mm(2), p<0.001) and the cardiac myosin-positive area (21.7%+/-8.4% vs.
      13.2%+/-4.4%, p<0.001) of the infarct border zone. In addition, significant
      amelioration of left ventricular (LV) remodeling (thickness of the LV posterior
      walls) (0.84+/-0.11 mm vs. 0.61+/-0.08 mm, p<0.001) was also observed at the same
      time compared with the control group. CONCLUSIONS: PMSNs-siCCR2-mediated CCR2
      gene silencing in Ly6C(high) monocytes improved the effectiveness of MSC
      transplantation and selectively ameliorated myocardial remodeling after AMI.
      These results suggest that PMSNs-siCCR2 could potentially be used to develop an
      anti-inflammatory therapy for post-AMI MSC transplantation.

PMID- 26199647
TI  - Superior Performance of Aptamer in Tumor Penetration over Antibody: Implication
      of Aptamer-Based Theranostics in Solid Tumors.
AB  - Insufficient penetration of therapeutic agents into tumor tissues results in
      inadequate drug distribution and lower intracellular concentration of drugs,
      leading to the increase of drug resistance and resultant failure of cancer
      treatment. Targeted drug delivery to solid tumors followed by complete drug
      penetration and durable retention will significantly improve clinical outcomes of
      cancer therapy. Monoclonal antibodies have been commonly used in clinic for
      cancer treatment, but their limitation of penetrating into tumor tissues still
      remains because of their large size. Aptamers, as "chemical antibodies", are 15
      20 times smaller than antibodies. To explore whether aptamers are superior to
      antibodies in terms of tumor penetration, we carried out the first comprehensive
      study to compare the performance of an EpCAM aptamer with an EpCAM antibody in
      theranostic applications. Penetration and retention were studied in in vitro
      three-dimensional tumorspheres, in vivo live animal imaging and mouse colorectal
      cancer xenograft model. We found that the EpCAM aptamer can not only effectively
      penetrate into the tumorsphere cores but can also be retained by tumor sphere
      cells for at least 24 h, while limited tumor penetration by EpCAM antibody was
      observed after 4 h incubation. As observed from in vivo live animal imaging,
      EpCAM aptamers displayed a maximum tumor uptake at around 10 min followed by a
      rapid clearance after 80 min, while the signal of peak uptake and disappearance
      of antibody appeared at 3 h and 6 h after intravenous injection, respectively.
      The signal of PEGylated EpCAM aptamers in xenograft tumors was sustained for 26
      h, which was 4.3-fold longer than that of the EpCAM antibody. Consistently, there
      were 1.67-fold and 6.6-fold higher accumulation of PEGylated aptamer in xenograft
      tumors than that of antibody, at 3 h and 24 h after intravenous administration,
      respectively. In addition, the aptamer achieved at least a 4-time better tumor
      penetration in xenograft tumors than that of the antibody at a 200 MUm distances
      from the blood vessels 3 h after intravenous injection. Taken together, these
      data indicate that aptmers are superior to antibodies in cancer theranostics due
      to their better tumor penetration, more homogeneous distribution and longer
      retention in tumor sites. Thus, aptamers are promising agents for targeted tumor
      therapeutics and molecular imaging. 

PMID- 26199648
TI  - Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin
      targeted Gold Nanoparticles.
AB  - Computed tomography (CT) is the current standard for time-critical decision
      making in stroke patients, informing decisions on thrombolytic therapy with
      tissue plasminogen activator (tPA), which has a narrow therapeutic index. We
      aimed to develop a CT-based method to directly visualize cerebrovascular thrombi
      and guide thrombolytic therapy. Glycol-chitosan-coated gold nanoparticles (GC
      AuNPs) were synthesized and conjugated to fibrin-targeting peptides, forming fib
      GC-AuNP. This targeted imaging agent and non-targeted control agent were
      characterized in vitro and in vivo in C57Bl/6 mice (n = 107) with FeCl3-induced
      carotid thrombosis and/or embolic ischemic stroke. Fibrin-binding capacity was
      superior with fib-GC-AuNPs compared to GC-AuNPs, with thrombi visualized as high
      density on microCT (mCT). mCT imaging using fib-GC-AuNP allowed the prompt
      detection and quantification of cerebral thrombi, and monitoring of tPA-mediated
      thrombolytic effect, which reflected histological stroke outcome. Furthermore,
      recurrent thrombosis could be diagnosed by mCT without further nanoparticle
      administration for up to 3 weeks. fib-GC-AuNP-based direct cerebral thrombus
      imaging greatly enhance the value and information obtainable by regular CT, has
      multiple uses in basic / translational vascular research, and will likely allow
      personalized thrombolytic therapy in clinic by a) optimizing tPA-dosing to match
      thrombus burden, b) enabling the rational triage of patients to more radical
      therapies such as endovascular clot-retrieval, and c) potentially serving as a
      theranostic platform for targeted delivery of concurrent thrombolysis. 

PMID- 26199649
TI  - Pilot Prospective Evaluation of (18)F-Alfatide II for Detection of Skeletal
      Metastases.
AB  - This pilot prospective evaluation study is to verify the efficiency of (18)F
      Alfatide II, a specific PET imaging agent for integrin alphavbeta3, in detecting
      bone metastasis in human, with comparison to (18)F-FDG PET. Thirty recruited
      patients underwent (18)F-FDG and (18)F-alfatide II PET/CT successively within
      days. The final diagnosis of bone lesions was established based on the
      comprehensive assessment of all available data and clinical follow-up, which fall
      into four groups: osteolytic, osteoblastic, mixed and bone marrow. Visual
      analysis and quantification of SUVmax were performed to compare the detection
      sensitivity of (18)F-Alfatide II and (18)F-FDG PET. Eleven patients were found to
      have a total of 126 bone metastasis lesions. (18)F-Alfatide II PET can detect the
      bone metastatic lesions with good contrast and higher sensitivity (positive rate
      of 92%) than (18)F-FDG PET (77%). Especially, (18)F-Alfatide II PET showed
      superiority to (18)F-FDG PET in detecting osteoblastic (70% vs. 53%) and bone
      marrow metastatic lesions (98% vs. 77%). In conclusion, (18)F-Alfatide II PET/CT
      can be used to detect skeletal and bone marrow metastases, with nearly 100%
      sensitivity in osteolytic, mixed and bone marrow lesions. The sensitivity of
      (18)F-Alfatide II PET/CT in osteoblastic metastases is relatively low but still
      significantly higher than that of (18)F-FDG PET/CT. This pilot clinical study
      warrants the further application of (18)F-Alfatide II PET/CT in metastatic lesion
      detection, patient management and drug therapy response monitoring. 

PMID- 26199651
TI  - Chiroptical properties of 1,3-diphenylallene-anchored tetrathiafulvalene and its
      polymer synthesis.
AB  - A novel tetrathiafulvalene dimer, bridged by a chiral 1,3-diphenylallene
      framework, has been prepared as an optically active compound having strong
      chiroptical properties. Although a chiral allene bearing strong electron-donating
      group(s) often undergoes slow photoracemization even in daylight, the present
      allene is totally configurationally stable under ordinary conditions. Each isomer
      possesses pronounced chiroptical properties in its ECD spectra reflecting the
      chiral allene framework. Moreover, the elongation of the chiral main chain was
      also carried out by direct C-H activation of the TTF unit, and the chiroptical
      properties of the resulting polymer were also investigated. 

PMID- 26199652
TI  - Properties of PTFE tape as a semipermeable membrane in fluorous reactions.
AB  - In a PTFE tape phase-vanishing reaction (PV-PTFE), a delivery tube sealed with
      PTFE tape is inserted into a vessel which contains the substrate. The reagent
      diffuses across the PTFE tape barrier into the reaction vessel. PTFE co-polymer
      films have been found to exhibit selective permeability towards organic
      compounds, which was affected by the presence of solvents. In this study, we
      attempted to establish general trends of permeability of PTFE tape to different
      compounds and to better describe the process of solvent transport in PV-PTFE
      bromination reactions. Though PTFE tape has been reported as impermeable to some
      compounds, such as dimethyl phthalate, solvent adsorption to the tape altered its
      permeability and allowed diffusion through channels of solvent within the PTFE
      tape. In this case, the solvent-filled pores of the PTFE tape are chemically more
      akin to the adsorbed solvent rather than to the PTFE fluorous structure. The
      solvent uptake effect, which was frequently observed in the course of PV-PTFE
      reactions, can be related to the surface tension of the solvent and the polarity
      of the solvent relative to the reagent. The lack of pores in bulk PTFE prevents
      solvents from altering its permeability and, therefore, bulk PTFE is impermeable
      to most solvents and reagents. However, bromine, which is soluble in liquid
      fluorous media, diffused through the bulk PTFE. A better understanding of the
      PTFE phase barrier will make it possible to further optimize the PV-PTFE reaction
      design. 

PMID- 26199653
TI  - Highly selective palladium-benzothiazole carbene-catalyzed allylation of active
      methylene compounds under neutral conditions.
AB  - The Pd-benzothiazol-2-ylidene complex I was found to be a chemoselective catalyst
      for the Tsuji-Trost allylation of active methylene compounds carried out under
      neutral conditions and using carbonates as allylating agents. The proposed
      protocol consists in a simplified procedure adopting an in situ prepared catalyst
      from Pd2dba3 and 3-methylbenzothiazolium salt V as precursors. A comparison of
      the performance of benzothiazole carbene with phosphanes and an analogous
      imidazolium carbene ligand is also proposed. 

PMID- 26199654
TI  - A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles.
AB  - A short and robust approach for the synthesis of 2-(hetero)aryl substituted
      thieno[2,3-b]indoles from easily available 1-alkylisatins and acetylated
      (hetero)arenes has been advanced. The two-step procedure includes the "aldol
      crotonic" type of condensation of the starting materials, followed by treatment
      of the intermediate 3-(2-oxo-2-(hetero)arylethylidene)indolin-2-ones with
      Lawesson's reagent. The latter process involves two sequential reactions, namely
      reduction of the C=C ethylidene double bond of the intermediate indolin-2-ones
      followed by the Paal-Knorr cyclization, thus affording tricyclic thieno[2,3
      b]indoles. 

PMID- 26199650
TI  - MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and
      Therapeutic Tools for Breast Cancer.
AB  - Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression
      of several human cancers, including breast cancer (BC), as strong evidence has
      been found that miRNAs can act as oncogenes or tumor suppressor genes. This
      review presents the state of the art on the role of miRNAs in the diagnosis,
      prognosis, and therapy of BC. Based on the results obtained in the last decade,
      some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b,
      and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of
      therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important
      roles in the control of BC hallmark functions such as invasion, metastasis,
      proliferation, resting death, apoptosis, and genomic instability. Other miRNAs
      are of interest as new, easily accessible, affordable, non-invasive tools for the
      personalized management of patients with BC because they are circulating in body
      fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA
      profiles are showing better diagnostic and prognostic performance as well as
      better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also
      promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and
      other miRNAs are showing a fundamental role in modulation of the response to
      other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21,
      miR34a, miR195, miR200c, and miR203 in combination with chemotherapy). 

PMID- 26199655
TI  - Radical-mediated dehydrative preparation of cyclic imides using (NH4)2S2O8-DMSO:
      application to the synthesis of vernakalant.
AB  - Ammonium persulfate-dimethyl sulfoxide (APS-DMSO) has been developed as an
      efficient and new dehydrating reagent for a convenient one-pot process for the
      synthesis of miscellaneous cyclic imides in high yields starting from readily
      available primary amines and cyclic anhydrides. A plausible radical mechanism
      involving DMSO has been proposed. The application of this facile one-pot imide
      forming process has been demonstrated for a practical synthesis of vernakalant. 

PMID- 26199656
TI  - Novel carbocationic rearrangements of 1-styrylpropargyl alcohols.
AB  - The dehydration and subsequent cyclization reactions of 1-styrylpropargyl
      alcohols was examined. In the course of these studies, numerous scaffolds were
      synthesized, including a furan, a cyclopentenone, an acyclic enone and even a
      naphthalenone. The diversity of these structural motifs lies in novel cascades of
      reactions originating from a common carbocationic manifold. 

PMID- 26199657
TI  - Glycoluril-tetrathiafulvalene molecular clips: on the influence of electronic and
      spatial properties for binding neutral accepting guests.
AB  - Glycoluril-based molecular clips incorporating tetrathiafulvalene (TTF) sidewalls
      have been synthesized through different strategies with the aim of investigating
      the effect of electrochemical and spatial properties for binding neutral
      accepting guests. We have in particular focused our study on the spacer extension
      in order to tune the intramolecular TTF...TTF distance within the clip and,
      consequently, the redox behavior of the receptor. Carried out at different
      concentrations in solution, electrochemical and spectroelectrochemical
      experiments provide evidence of mixed-valence and/or pi-dimer intermolecular
      interactions between TTF units from two closed clips. The stepwise oxidation of
      each molecular clip involves an electrochemical mechanism with three one-electron
      processes and two charge-coupled chemical reactions, a scheme which is supported
      by electrochemical simulations. The fine-tunable pi-donating ability of the TTF
      units and the cavity size allow to control binding interaction towards a strong
      electron acceptor such as tetrafluorotetracyanoquinodimethane (F4-TCNQ) or a
      weaker electron acceptor such as 1,3-dinitrobenzene (m-DNB). 

PMID- 26199658
TI  - Quarternization of 3-azido-1-propyne oligomers obtained by copper(I)-catalyzed
      azide-alkyne cycloaddition polymerization.
AB  - 3-Azido-1-propyne oligomer (oligoAP) samples, prepared by copper(I)-catalyzed
      azide-alkyne cycloaddition (CuAAC) polymerization, were quarternized
      quantitatively with methyl iodide in sulfolane at 60  degrees C to obtain soluble
      oligomers. The conformation of the quarternized oligoAP in dilute DMSO-d 6
      solution was examined by pulse-field-gradient spin-echo NMR based on the touched
      bead model. 

PMID- 26199659
TI  - Donor-acceptor type co-crystals of arylthio-substituted tetrathiafulvalenes and
      fullerenes.
AB  - A series of donor-acceptor type co-crystals of fullerene (as the acceptor) and
      arylthio-substituted tetrathiafulvalene derivatives (Ar-S-TTF, as the donor) were
      prepared and their structural features were thoroughly investigated. The
      formation of co-crystals relies on the flexibility of Ar-S-TTF and the size
      matches between Ar-S-TTF and fullerene. Regarding their compositions, the studied
      co-crystals can be divided into two types, where types I and II have
      donor:acceptor ratios of 1:1 and 1:2, respectively. Multiple intermolecular
      interactions are observed between the donor and acceptor, which act to stabilize
      the structures of the resulting co-crystals. In the type I co-crystals, the
      fullerene molecule is surrounded by four Ar-S-TTF molecules, that is, two Ar-S
      TTF molecules form a sandwich structure with one fullerene molecule and the other
      two Ar-S-TTF molecules interact with the fullerene molecule along their lateral
      axes. In the type II co-crystals, one fullerene molecule has the donor-acceptor
      mode similar to that in type I, whereas the other fullerene molecule is
      substantially surrounded by the aryl groups on Ar-S-TTF molecules and the solvent
      molecules. 

PMID- 26199660
TI  - A hybrid electron donor comprising cyclopentadithiophene and dithiafulvenyl for
      dye-sensitized solar cells.
AB  - Two new photosensitizers featured with a cyanoacrylic acid electron acceptor (A)
      and a hybrid electron donor (D) of cyclopentadithiophene and dithiafulvenyl,
      either directly linked or separated by a phenyl ring, were synthesized and
      characterized. Both of them undergo two reversible oxidations and strongly absorb
      in the visible spectral region due to a photo-induced intramolecular charge
      transfer (ICT) transition. To a great extent, the electronic interaction between
      the D and A units is affected by the presence of a phenyl spacer. Without a
      phenyl ring, the D unit appears more difficult to oxidize due to a strong
      electron-withdrawing effect of the A moiety. In sharp contrast, the insertion of
      the phenyl ring between the D and A units leads to a broken pi-conjugation and
      therefore, the oxidation potentials remain almost unchanged compared to those of
      an analogue without the A group, suggesting that the electronic coupling between
      D and A units is relatively weak. As a consequence, the lowest-energy absorption
      band shows a slight hypsochromic shift upon the addition of the phenyl spacer,
      indicative of an increased HOMO-LUMO gap. In turn, the direct linkage of D and A
      units leads to an effective pi-conjugation, thus substantially lowering the HOMO
      LUMO gap. Moreover, the application in dye-sensitized solar cells was
      investigated, showing that the power conversion efficiency increases by the
      insertion of the phenyl unit. 

PMID- 26199661
TI  - Synthesis of novel N-cyclopentenyl-lactams using the Aube reaction.
AB  - A novel and convenient method utilizing the Aube reaction to access a new class
      of compounds that are similar to carbocyclic nucleosides is reported. The azido
      alcohol derived from Vince lactam undergoes the Aube reaction with various cyclic
      ketones to give cyclopentenyl-substituted lactams. Upon dihydroxylation, this
      affords the N-cyclopentenyl-lactam compounds in racemic form. Given the numerous
      uses of nucleosides and related compounds, we were interested in the synthesis of
      carbocylic nucleoside mimics. The attempts and results are described herein. 

PMID- 26199662
TI  - Single-molecule conductance of a chemically modified, pi-extended
      tetrathiafulvalene and its charge-transfer complex with F4TCNQ.
AB  - We describe the synthesis and single-molecule electrical transport properties of
      a molecular wire containing a pi-extended tetrathiafulvalene (exTTF) group and
      its charge-transfer complex with F4TCNQ. We form single-molecule junctions using
      the in situ break junction technique using a homebuilt scanning tunneling
      microscope with a range of conductance between 10 G0 down to 10(-7) G0. Within
      this range we do not observe a clear conductance signature of the neutral parent
      molecule, suggesting either that its conductance is too low or that it does not
      form a stable junction. Conversely, we do find a clear conductance signature in
      the experiments carried out on the charge-transfer complex. Due to the fact we
      expected this species to have a higher conductance than the neutral molecule, we
      believe this supports the idea that the conductance of the neutral molecule is
      very low, below our measurement sensitivity. This idea is further supported by
      theoretical calculations. To the best of our knowledge, these are the first
      reported single-molecule conductance measurements on a molecular charge-transfer
      species. 

PMID- 26199663
TI  - Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a
      pyridine unit respectively.
AB  - The three possible structural isomers of 4-(pyridyl)pyrimidine were employed for
      the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3
      dipolar cycloaddition reaction of their corresponding N-ylides generated in situ
      from their corresponding cycloimmonium bromides. In the case of 4-(3
      pyridyl)pyrimidine and 4-(4-pyridyl)pyrimidine the quaternization reactions occur
      as expected at the pyridine nitrogen atom leading to pyridinium bromides and
      consequently to new indolizines via the corresponding pyridinium N-ylides.
      However, in the case of 4-(2-pyridyl)pyrimidine the steric hindrance directs the
      reaction to the pyrimidinium N-ylides and, subsequently, to the formation of the
      pyrrolo[1,2-c]pyrimidines. The new pyrrolo[1,2-c]pyrimidines and the new
      indolizines were structurally characterized through NMR spectroscopy. The X-ray
      structures of two of the starting materials, 4-(2-pyridyl)pyrimidine and 4-(4
      pyridyl)pyrimidine, are also reported. 

PMID- 26199665
TI  - Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?
AB  - The Amadori rearrangement was employed for the synthesis of C-glycosyl-type D
      mannoside analogues, namely 1-propargylamino- and 1-phenylamino-1-deoxy-alpha-D
      manno-heptopyranose. They were investigated as ligands of type 1-fimbriated E.
      coli bacteria by means of molecular docking and bacterial adhesion studies. It
      turns out that Amadori rearrangement products have a limited activity as
      inhibitors of bacterial adhesion because the beta-C-glycosidically linked
      aglycone considerably hampers complexation within the carbohydrate binding site
      of the type 1-fimbrial lectin FimH. 

PMID- 26199664
TI  - Synthesis of photoresponsive cholesterol-based azobenzene organogels: dependence
      on different spacer lengths.
AB  - A series of azobenzene-cholesterol organogel compounds (M 0 -M 12 ) with
      different spacers were designed and synthesized. The molecular structures were
      confirmed by (1)H NMR and (13)C NMR spectroscopy. The rapid and reversible
      photoresponsive properties of the compounds were investigated by UV-vis
      spectroscopy. Their thermal phase behaviors were studied by DSC. The length of
      the spacer plays a crucial role in the gelation. Compound M 6 is the only one
      that can gelate in ethanol, isopropanol and 1-butanol and the reversible gel-sol
      transitions are also investigated. To obtain visual insight into the
      microstructure of the gels, the typical structures of the xerogels were studied
      by SEM. Morphologies of the aggregates change from flower-like, network and rod
      with different sizes. By using IR and XRD characterization, it is found that
      intermolecular H-bonding, the solvents and van der Waals interaction are the main
      contributions to the specific superstructure. 

PMID- 26199666
TI  - Regioselective synthesis of chiral dimethyl-bis(ethylenedithio)tetrathiafulvalene
      sulfones.
AB  - Enantiopure (R,R) and (S,S)-dimethyl-bis(ethylenedithio)tetrathiafulvalene
      monosulfones have been synthesized by the aerial oxidation of the chiral
      dithiolates generated from the propionitrile-protected precursors. Both
      enantiomers crystallize in the orthorhombic chiral space group P212121. They show
      a boat-type conformation of the TTF moiety, a rather rigid dithiin sulfone ring
      and the methyl groups in a bisequatorial conformation. Cyclic voltammetry
      measurements indicate fully reversible oxidation in radical cation and dication
      species. 

PMID- 26199667
TI  - Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes.
AB  - The electron-donor and unique redox properties of the tetrathiafulvalene (TTF, 1)
      moiety have led to diverse applications in many areas of chemistry.
      Monopyrrolotetrathiafulvalenes (MPTTFs, 4) and bispyrrolotetrathiafulvalenes
      (BPTTFs, 5) are useful structural motifs and have found widespread use in fields
      such as supramolecular chemistry and molecular electronics. Protocols enabling
      the synthesis of functionalised MPTTFs and BPTTFs are therefore of broad
      interest. Herein, we present the synthesis of a range of functionalised MPTTF and
      BPTTF species. Firstly, the large-scale preparation of the precursor species N
      tosyl-(1,3)-dithiolo[4,5-c]pyrrole-2-one (6) is described, as well as the
      synthesis of the analogue N-tosyl-4,6-dimethyl-(1,3)-dithiolo[4,5-c]pyrrole-2-one
      (7). Thereafter, we show how 6 and 7 can be used to prepare BPTTFs using
      homocoupling reactions and functionalised MPTTFs using cross-coupling reactions
      with a variety of 1,3-dithiole-2-thiones (19). Subsequently, the incorporation of
      more complex functionality is discussed. We show how the 2-cyanoethyl protecting
      group can be used to afford MPTTFs functionalised with thioethers, exemplified by
      a series of ethylene glycol derivatives. Additionally, the merits of 1,8
      diazabicyclo[5.4.0]undec-7-ene (DBU) as an alternative to the most common
      deprotecting agent, CsOH.H2O are discussed. Finally, we show how a copper
      mediated Ullman-type reaction can be applied to the N-arylation of MPTTFs and
      BPTTFs using a variety of aryl halides. 

PMID- 26199668
TI  - Hybrid macrocycle formation and spiro annulation on cis-syn-cis
      tricyclo[6.3.0.0(2,6)]undeca-3,11-dione and its congeners via ring-closing
      metathesis.
AB  - We have developed a simple methodology to transform cis-syn-cis-triquinane
      derivative 2 into the diindole based macrocycle 6 involving Fischer indolization
      and ring-closing metathesis (RCM). Various spiro-polyquinane derivatives have
      been assembled via RCM as a key step. 

PMID- 26199669
TI  - Azobenzene-based inhibitors of human carbonic anhydrase II.
AB  - Aryl sulfonamides are a widely used drug class for the inhibition of carbonic
      anhydrases. In the context of our program of photochromic pharmacophores we were
      interested in the exploration of azobenzene-containing sulfonamides to block the
      catalytic activity of human carbonic anhydrase II (hCAII). Herein, we report the
      synthesis and in vitro evaluation of a small library of nine photochromic
      sulfonamides towards hCAII. All molecules are azobenzene-4-sulfonamides, which
      are substituted by different functional groups in the 4'-position and were
      characterized by X-ray crystallography. We aimed to investigate the influence of
      electron-donating or electron-withdrawing substituents on the inhibitory constant
      K i. With the aid of an hCAII crystal structure bound to one of the synthesized
      azobenzenes, we found that the electronic structure does not strongly affect
      inhibition. Taken together, all compounds are strong blockers of hCAII with K i =
      25-65 nM that are potentially photochromic and thus combine studies from chemical
      synthesis, crystallography and enzyme kinetics. 

PMID- 26199670
TI  - New tris- and pentakis-fused donors containing extended tetrathiafulvalenes: New
      positive electrode materials for rechargeable batteries.
AB  - Derivatives of tris-fused TTF extended with two ethanediylidenes (5), tris- and
      pentakis-fused TTFs extended with two thiophene-2,5-diylidenes (6-9) were
      successfully synthesized. Cyclic voltammograms of the tetrakis(n-hexylthio)
      derivative of 5 and 7 (5d, 7d) consisted of two pairs of two-electron redox waves
      and two pairs of one-electron redox waves. On the other hand, four pairs of two
      electron redox waves and two pairs of one-electron redox waves were observed for
      the tetrakis(n-hexylthio) derivative of 9 (9d). Coin-type cells using the
      bis(ethylenedithio) derivatives of 5 (5b), 6 (6b) and the tetrakis(methylthio)
      derivatives of 5 (5c) and 8 (8c) as positive electrode materials showed initial
      discharge capacities of 157-190 mAh g(-1) and initial energy densities of 535-680
      mAh g(-1). The discharge capacities after 40 cycles were 64-86% of the initial
      discharge capacities. 

PMID- 26199671
TI  - Thiazole-induced rigidification in substituted dithieno-tetrathiafulvalene: the
      effect of planarisation on charge transport properties.
AB  - Two novel tetrathiafulvalene (TTF) containing compounds 1 and 2 have been
      synthesised via a four-fold Stille coupling between a tetrabromo-dithienoTTF 5
      and stannylated thiophene 6 or thiazole 4. The optical and electrochemical
      properties of compounds 1 and 2 have been measured by UV-vis spectroscopy and
      cyclic voltammetry and the results compared with density functional theory (DFT)
      calculations to confirm the observed properties. Organic field effect transistor
      (OFET) devices fabricated from 1 and 2 demonstrated that the substitution of
      thiophene units for thiazoles was found to increase the observed charge
      transport, which is attributed to induced planarity through S-N interactions of
      adjacent thiazole nitrogen atoms and TTF sulfur atoms and better packing in the
      bulk. 

PMID- 26199672
TI  - Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized
      using a Mizoroki-Heck cross-coupling reaction.
AB  - Cinnamic acid derivatives bearing a nitroxyl moiety (2,2,6,6-tetramethyl-1-oxyl-4
      piperidyl 3-E-aryl acrylates) were synthesized in 30-100% yield using a Mizoroki
      Heck cross-coupling reaction between 4-acryloyloxy-2,2,6,6-tetramethylpiperidine
      1-oxyl and iodobenzene derivatives in the presence of palladium(II) acetate
      coordinated with a tri(o-tolyl)phosphine ligand immobilized in a polyurea matrix.

PMID- 26199673
TI  - Cathodic hydrodimerization of nitroolefins.
AB  - Nitroalkenes are easily accessible in high variety by condensation of aldehydes
      with aliphatic nitroalkanes. They belong to the group of activated alkenes that
      can be hydrodimerized by cathodic reduction. There are many olefins with
      different electron withdrawing groups used for cathodic hydrodimerization, but
      not much is known about the behaviour of the nitro group. Synthetic applications
      of this group could profit from the easy access to nitroolefins in large variety,
      the C-C bond formation with the introduction of two nitro groups in a 1,4
      distance and the conversions of the nitro group by reduction to oximes and
      amines, the conversion into aldehydes and ketones via the Nef reaction and base
      catalyzed condensations at the acidic CH bond. Eight 1-aryl-2-nitro-1-propenes
      have been electrolyzed in an undivided electrolysis cell to afford 2,5-dinitro
      3,4-diaryl hexanes in high yield. The 4-methoxy-, 4-trifluoromethyl-, 2-chloro-
      and 2,6-difluorophenyl group and furthermore the 2-furyl and 2-pyrrolyl group
      have been applied. The reaction is chemoselective as only the double bond but not
      the nitro group undergoes reaction, is regioselective as a beta,beta-coupling
      with regard to the nitro group and forms preferentially two out of six possible
      diastereomers as major products. 

PMID- 26199674
TI  - Identifying CpG sites associated with eczema via random forest screening of
      epigenome-scale DNA methylation.
AB  - BACKGROUND: The prevalence of eczema is increasing in industrialized nations.
      Limited evidence has shown the association of DNA methylation (DNA-M) with
      eczema. We explored this association at the epigenome-scale to better understand
      the role of DNA-M. Data from the first generation (F1) of the Isle of Wight (IoW)
      birth cohort participants and the second generation (F2) were examined in our
      study. Epigenome-scale DNA methylation of F1 at age 18 years and F2 in cord blood
      was measured using the Illumina Infinium HumanMethylation450 Beadchip. A total of
      307,357 cytosine-phosphate-guanine sites (CpGs) in the F1 generation were
      screened via recursive random forest (RF) for their potential association with
      eczema at age 18. Functional enrichment and pathway analysis of resulting genes
      were carried out using DAVID gene functional classification tool. Log-linear
      models were performed in F1 to corroborate the identified CpGs. Findings in F1
      were further replicated in F2. RESULTS: The recursive RF yielded 140 CpGs, 88 of
      which showed statistically significant associations with eczema at age 18,
      corroborated by log-linear models after controlling for false discovery rate
      (FDR) of 0.05. These CpGs were enriched among many biological pathways, including
      pathways related to creating transcriptional variety and pathways mechanistically
      linked to eczema such as cadherins, cell adhesion, gap junctions, tight
      junctions, melanogenesis, and apoptosis. In the F2 generation, about half of the
      83 CpGs identified in F1 showed the same direction of association with eczema
      risk as in F1, of which two CpGs were significantly associated with eczema risk,
      cg04850479 of the PROZ gene (risk ratio (RR) = 15.1 in F1, 95 % confidence
      interval (CI) 1.71, 79.5; RR = 6.82 in F2, 95 % CI 1.52, 30.62) and cg01427769 of
      the NEU1 gene (RR = 0.13 in F1, 95 % CI 0.03, 0.46; RR = 0.09 in F2, 95 % CI
      0.03, 0.36). CONCLUSIONS: Via epigenome-scaled analyses using recursive RF
      followed by log-linear models, we identified 88 CpGs associated with eczema in
      F1, of which 41 were replicated in F2. Several identified CpGs are located within
      genes in biological pathways relating to skin barrier integrity, which is central
      to the pathogenesis of eczema. Novel genes associated with eczema risk were
      identified (e.g., the PROZ and NEU1 genes).

PMID- 26199676
TI  - A Combination of Low Doses of Fluvastatin and Valsartan Decreases Arterial
      Stiffness in Patients After Myocardial Infarction: A Pilot Study.
AB  - BACKGROUND: Despite optimum treatment, patients who experience myocardial
      infarction are still at high risk for future events. OBJECTIVE: We evaluated the
      effect of 30 days of treatment with combination of low, subtherapeutic doses of
      fluvastatin and valsartan on arterial stiffness in patients after myocardial
      infarction, a therapy that has not been used yet. METHODS: Fourteen male patients
      with a history of myocardial infarction were enrolled into a pilot double-blind
      randomized controlled study. They were allocated to receive 10 mg fluvastatin and
      20 mg valsartan or placebo for 30 days in addition to their regular
      pharmacotherapy. Carotid-femoral pulse wave velocity was measured on inclusion,
      after 30 days, and after 3 months. RESULTS: Mean (SD) carotid-femoral pulse wave
      velocity decreased significantly in the treatment group after 30 days and
      persisted at lower values after 3 months (from 8.4 [1.5] m/sec to 7.3 [1.1] m/sec
      to 7.2 [0.8] m/sec; P < 0.05). The 95% CI for decrease after 30 days in the
      treatment group was 0.5-1.6. Only nonsignificant changes were observed in the
      control group. Serum lipid levels and arterial blood pressure did not change
      significantly in any group. CONCLUSIONS: The treatment resulted in a significant
      and sustained improvement of arterial stiffness in male patients with a history
      of myocardial infarction, which highlights the need for further study of this new
      approach.

PMID- 26199675
TI  - Circulating microRNA-144-5p is associated with depressive disorders.
AB  - BACKGROUND: Depressive/anxiety disorders are the most common types of mental
      illnesses in the world. The present study was the first to explore the
      association between plasma microRNAs (miRNAs) and depression/anxiety in primary
      care patients. RESULTS: In total, 169 patients (aged 20-64 years) from 16 primary
      health centers were enrolled in the present study. The healthy controls were
      consisted of 52 individuals. We first performed miRNA screening of plasma samples
      from 11 patients using a Serum/Plasma Focus microRNA Panel comprising 179 miRNA
      primer sets. Six miRNAs were differentially expressed and were then validated by
      quantitative real-time (qRT)-PCR in the entire study cohort. The mean plasma miR
      144-5p level in the depression/anxiety patients increased significantly compared
      to baseline (p < 0.0001) after the 8-week follow-up. No significant associations
      were found between the differentially expressed miRNAs and a change in the
      Montgomery-Asberg Depression Rating Scale (MADRS-S) score after the follow-up. In
      linear regression analysis, the plasma miR-144-5p expression level was inversely
      related to the depression score (MADRS-S) (beta = -0.02, p < 0.01), after
      adjustment for sex and age, at baseline. In addition, plasma miR-144-5p levels at
      baseline in the depression/anxiety patients were significantly lower compared
      with the healthy controls (p < 0.001). CONCLUSIONS: Our findings show that plasma
      miR-144-5p levels are associated with depressive symptoms. Although confirmatory
      analyses are required, plasma miRNA-144-5p is a potential peripheral biomarker
      for pathologic processes related to depression.

PMID- 26199677
TI  - Novel Antioxidant Tripeptide "ACQ" Can Prevent UV-Induced Cell Death and Preserve
      the Number of Epidermal Stem Cells.
AB  - We found that tripeptide "ACQ: alanine-cysteine-glutamine" has significant DPPH
      scavenging activity compared to that of glutathione. Antioxidant effects of ACQ
      were tested in in vitro and in vivo models. When treated with H2O2, mock treated
      fibroblasts and keratinocytes showed strong staining by H2DCFA. But, ACQ showed
      good protective effects against hydrogen peroxide treatment. When mice were fed
      for 2 or 4 weeks, similar protective effects were observed. In the control group,
      epidermis was severely damaged by UV irradiation and apoptotic keratinocytes were
      observed. There were also numerous TUNEL positive cells. But in the ACQ group,
      epidermis became thicker and there was no sign of severe damage. Interestingly,
      the number of p63 cells was also higher in ACQ fed mice. To confirm the stem cell
      rescuing effects of ACQ, three-dimensional skin samples were constructed. Results
      showed that ACQ increased the expression of integrin alpha6 and the number of p63
      positive cells. These findings showed that ACQ has good antioxidant activity and
      may increase stem cell activities by the regulation of integrin alpha6. 

PMID- 26199678
TI  - Hsp20 Protects against Oxygen-Glucose Deprivation/Reperfusion-Induced Golgi
      Fragmentation and Apoptosis through Fas/FasL Pathway.
AB  - Cerebral ischemia-reperfusion injury plays an important role in the development
      of tissue injury after acute ischemic stroke. Finding effective neuroprotective
      agents has become a priority in the treatment of ischemic stroke. The Golgi
      apparatus (GA) is a pivotal organelle and its protection is an attractive target
      in the treatment of cerebral ischemia-reperfusion injury. Protective effects of
      Hsp20, a potential cytoprotective agent due to its chaperone-like activity and
      involvement in regulation of many vital processes, on GA were assessed in an
      ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were
      subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces
      Golgi fragmentation, apoptosis, and p115 cleavage in N2a cells. However,
      transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation
      and apoptosis. Hsp20 interacts with Bax, decreases FasL and Bax expression, and
      inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. Our data
      demonstrate that increased Hsp20 expression protects against OGDR-induced Golgi
      fragmentation and apoptosis, likely through interaction with Bax and subsequent
      amelioration of the OGDR-induced elevation in p115 cleavage via the Fas/FasL
      signaling pathway. This neuroprotective potential of Hsp20 against OGDR insult
      and the underlying mechanism will pave the way for its potential clinical
      application for cerebral ischemia-reperfusion related disorders. 

PMID- 26199680
TI  - Single-Crystalline, Nanoporous Gallium Nitride Films With Fine Tuning of Pore
      Size for Stem Cell Engineering.
AB  - Single-crystalline nanoporous gallium nitride (GaN) thin films were fabricated
      with the pore size readily tunable in 20-100 nm. Uniform adhesion and spreading
      of human mesenchymal stem cells (hMSCs) seeded on these thin films peak on the
      surface with pore size of 30 nm. Substantial cell elongation emerges as pore size
      increases to ~80 nm. The osteogenic differentiation of hMSCs occurs
      preferentially on the films with 30 nm sized nanopores, which is correlated with
      the optimum condition for cell spreading, which suggests that adhesion,
      spreading, and stem cell differentiation are interlinked and might be coregulated
      by nanotopography.

PMID- 26199679
TI  - Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate
      Induced Airway Hyperresponsiveness in Rats.
AB  - The rate of atmospheric vanadium is constantly increasing due to fossil fuel
      combustion. This environmental pollution favours vanadium exposure in particular
      to its vanadate form, causing occupational bronchial asthma and bronchitis. Based
      on the well admitted bronchodilator properties of the pituitary adenylate cyclase
      activating polypeptide (PACAP), we investigated the ability of this neuropeptide
      to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to
      ammonium metavanadate aerosols (5 mg/m(3)/h) for 15 minutes induced 4 hours later
      an array of pathophysiological events, including increase of bronchial resistance
      and histological alterations, activation of proinflammatory alveolar macrophages,
      and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM) for
      10 minutes alleviated many of these deleterious effects as demonstrated by a
      decrease of bronchial resistance and histological restoration. PACAP reduced the
      level of expression of mRNA encoding inflammatory chemokines (MIP-1alpha, MIP-2,
      and KC) and cytokines (IL-1alpha and TNF-alpha) in alveolar macrophages and
      improved the antioxidant status. PACAP reverses the vanadate-induced airway
      hyperresponsiveness not only through its bronchodilator activity but also by
      counteracting the proinflammatory and prooxidative effects of the metal. Then,
      the development of stable analogs of PACAP could represent a promising
      therapeutic alternative for the treatment of inflammatory respiratory disorders.

PMID- 26199681
TI  - Electric-Field Enhanced Molecule Detection in Suspension on Assembled Plasmonic
      Arrays by Raman Spectroscopy.
AB  - One of the greatest challenges in surface enhanced Raman scattering (SERS)
      sensing is to detect biochemicals directly from suspension with ultrasensitivity.
      In this work, we employed strategically designed longitudinal nanocapsule
      structures with uniformly surface distributed Ag nanoparticles (Ag NPs) to dually
      focus and enhance SERS sensitivity of biochemicals in suspension assisted with
      electric fields. By tuning the reaction conditions, Ag NPs were synthesized and
      uniformly grown with optimized sizes and junctions on the surface of nanocapsules
      for well reproducible detection. The Ag NPs can further concentrate molecules
      from suspension due to induced electrokinetic effects in electric fields. As a
      result, the signals of Nile blue molecules can be enhanced by 34.4+/-3.1% at
      optimal alternating current (AC) frequencies and voltages compared to that
      without electric fields. This work demonstrates the dual roles of a new type of
      plasmonic NPs for molecule concentration and detection, which could inspire new
      Raman sensing devices for applications in microfluidics.

PMID- 26199682
TI  - The power of operon rearrangements for predicting functional associations.
AB  - In this mini-review I aim to make the case that operons might be the most
      powerful source for predicted associations among gene products. Such associations
      can help identify potential processes where the products of unannotated genes
      might play a role. The power of the operon for providing insight into functional
      associations stems from four features: (1) on average, around 60% of the genes in
      prokaryotes are associated into operons; (2) the functional associations between
      genes in operons tend to be highly conserved; (3) operons can be predicted with
      high accuracy by conservation of gene order and by the distances between adjacent
      genes in the same DNA strand; and (4) operons frequently reorganize, providing
      further insight into functional associations that would not be evident without
      these reorganization events. 

PMID- 26199683
TI  - Clinical Signs and Symptoms and Laboratory Findings of Methadone Poisoning in
      Children.
AB  - BACKGROUND: Poisoning accounts for about 7% of all accidents in children under 5
      years and is implicated in over 5% of all childhood deaths in developing
      countries. OBJECTIVES: Due to the potential risks of methadone poisoning in
      children and increased cases of methadone poisoning among Iranian children, this
      study was conducted to investigate the clinical signs and symptoms and laboratory
      findings of methadone toxicity in children. PATIENTS AND METHODS: The present
      retrospective, descriptive, cross-sectional study describes the clinical symptoms
      and signs and laboratory findings of methadone poisoning in children under 12
      years old in Shahid Beheshti Hospital, Kashan, during the years 2009 to 2013.
      RESULTS: Of 58 patients, 33 (56.9%) were male and 25 (43.1%) female (P = 0.294).
      The mean age of patients was 5.2 +/- 1.0 years. All the cases of poisoning
      happened with methadone syrup, due to unsafe keeping of methadone in mineral
      water bottles and containers of other drugs. Signs and symptoms included
      drowsiness (91.4 %), miosis (75.9%), vomiting (69.0%), ineffective breathing (any
      kind of breathing problem except apnea) (62.1%), apnea (53.4%), cyanosis (43.1%),
      seizure (8.6%), ataxia (6.9%) and delirium (3.4%). CONCLUSIONS: Keeping methadone
      in appropriate containers and warning methadone consumers about the dangerous
      side effects of its consumption and the symptoms of methadone poisoning in
      children may minimize the occurrence of this form of poisoning and its
      complications in children.

PMID- 26199684
TI  - Calcium Intake, Major Dietary Sources and Bone Health Indicators in Iranian
      Primary School Children.
AB  - BACKGROUND: Adequate calcium intake may have a crucial role with regards to
      prevention of many chronic diseases, including hypertension,
      hypercholesterolemia, different types of cancer, obesity and osteoporosis. In
      children, sufficient calcium intake is especially important to support the
      accelerated growth spurt during the preteen and teenage years and to increase
      bone mineral mass to lay the foundation for older age. OBJECTIVES: This study
      aimed to assess daily calcium intake in school-age children to ensure whether
      they fulfill the FGP dairy serving recommendations, the recommended levels of
      daily calcium intake and to assess the relationship between dietary calcium
      intake and major bone health indicators. PATIENTS AND METHODS: A total of 501
      Iranian school-age children were randomly selected. Calcium intake was assessed
      using a semi-quantitative food frequency questionnaire. Bone health indicators
      were also assessed. RESULTS: Dairy products contributed to 69.3% of the total
      calcium intake of the children. Daily adequate intake of calcium was achieved by
      17.8% of children. Only 29.8% met the Food guide pyramid recommendations for
      dairy intake. Dietary calcium intake was not significantly correlated with serum
      calcium and other selected biochemical indicators of bone health. CONCLUSIONS:
      The need for planning appropriate nutrition strategies for overcoming inadequate
      calcium intake in school age children in the city of Tehran is inevitable.

PMID- 26199685
TI  - The Prevalence of Diabetes and Prediabetes Among Elementary School Children in
      Birjand.
AB  - BACKGROUND: Diabetes is associated with increased cardiovascular disease,
      mortality and morbidity. OBJECTIVES: The present study aimed at assessing fasting
      blood sugar (FBS) in elementary school students in Birjand, 2012. MATERIALS AND
      METHODS: This cross-sectional and descriptive study was done on 1530 elementary
      school students who had been selected through multiple cluster sampling. FBS of
      these students was tested applying the enzymatic process. The obtained data was
      analyzed by means of SPSS software (v15) and statistical tests t and X(2).
      RESULTS: In this study, 833 girls and 697 boys were evaluated. Mean FBS of the
      whole study population was 86.9 +/- 8.8 mg/dL; FBS was higher in boys compared to
      girls. FBS of 1453 (95%) children was < 100 mg/dL, the mean being 85.8 +/- 6.8
      mg/dL. FBS of 698 (45.6%) students of the above population was 86-99 mg/dl. It
      was 100-125 mg/dL in 72 (4.7%) individuals. Five (0.3%) students had FBS >126
      mg/dL. Mean FBS increased in proportion to age, which was statistically
      significant. CONCLUSIONS: Although the prevalence of diabetes is not
      considerable; however, based on the relatively high portion of those children
      with high degree of blood glucose in the range in which the risk of diabetes and
      prediabetes in the following years rises dramatically, the need for further care
      of health authorities, an extensive screening activity, and undertaking
      intervening measures to prevent the epidemic of diabetes and consequently
      cardiovascular disease is emphasized.

PMID- 26199686
TI  - Agreement of Mixed Venous Carbon Dioxide Tension (PvCO2) and Transcutaneous
      Carbon Dioxide (PtCO2) Measurements in Ventilated Infants.
AB  - BACKGROUND: Noninvasive transcutaneous carbon dioxide monitoring has been shown
      to be accurate in infants and children, limited data are available to show the
      usefulness and limitations of partial transcutaneous carbon dioxide tension
      (PtCO2) value. OBJECTIVES: The current study prospectively determines the
      effectiveness and accuracy of PtCO2 measurements in newborns. MATERIALS AND
      METHODS: Venous blood gas sampling and monitoring of the PtCO2 level (TCM TOSCA,
      Radiometer) were done simultaneously. All measurements are performed on
      mechanically ventilated infants. Partial venous carbon dioxide tension (PvCO2)
      values divided into three groups according to hypocapnia (Group 1: < 4.68 kPa),
      normocapnia (Group 2: 4.68-7.33 kPa), hypercapnia (Group 3: > 7.33 kPa) and then
      PvCO2 and PtCO2 data within each group were compared separately. RESULTS: A total
      of 168 measurements of each PvCO2 and PtCO2 data were compared in three separated
      groups simultaneously (13 in Group 1, 118 in Group 2, and 37 in Group 3). A bias
      of more than +/- 0.7 kPa was considered unacceptable. PtCO2 was related to PvCO2
      with acceptable results between the two measurements in hypocapnia (mean
      difference 0.20 +/- 0.19 kPa) and normocapnia (0.002 +/- 0.30 kPa) groups. On the
      other hand in hypercapnia group PtCO2 values were statistically significant (P <
      0.001) and lower than PvCO2 data (mean difference 0.81 +/- 1.19 kPa).
      CONCLUSIONS: PtCO2 measurements have generally good agreement with PvCO2 in
      hypocapnic and normocapnic intubated infants but there are some limitations
      especially with high level of CO2 tension. Monitoring of PtCO2 is generally a
      useful non-invasive indicator of PvCO2 in hypocapnic and normocapnic infants.

PMID- 26199687
TI  - Epidemiological and Clinical Characteristics and Outcomes of Scorpion
      Envenomation in Hospitalized Children in Adiyaman, Turkey.

PMID- 26199688
TI  - Application of Lidocaine Spray for Tracheal Intubation in Neonates - A Clinical
      Trial Study.
AB  - BACKGROUND: Tracheal intubation is extremely distressing, painful, and may
      influence heart rate and blood pressure. Sedatives, analgesics, and muscle
      relaxants are not commonly used for intubation in neonates. OBJECTIVES: This
      study aimed to evaluate the effects of lidocaine spray as a non-intravenous drug
      before neonatal intubation on blood pressure, heart rate, oxygen saturation and
      time of intubation. PATIENTS AND METHODS: In a randomized, controlled study each
      neonate was randomly assigned to one of the two study groups by staffs who were
      not involved in the infant's care. The allocation concealment was kept in an
      opaque sealed envelope, and the investigators, the patient care team, and the
      assessors were blinded to the treatment allocation. The selected setting was NICU
      unit of a teaching hospital in Ilam city, Iran and participants were 60 neonates
      with indication of tracheal intubation with gestational age > 30 weeks. Patients
      in the treatment group received lidocaine spray and the placebo group received
      spray of normal saline prior to intubation. Main outcome measurements were the
      mean rates of blood pressure, heart rate, oxygen saturation, intubation time and
      lidocaine side effects were measured before and after intubation. RESULTS:
      Totally 60 newborns including 31 boys and 29 girls were entered into the study
      (drug group n = 30; placebo group n = 30). Boy/girl ratio in treatment and
      placebo groups were 1.3 and 0.88, respectively. Mean age +/- SD of participants
      was 34.1 +/- 24.8 hours (treatment: 35.3 +/- 25.7; placebo: 32.9 +/- 24.3; P <
      0.0001). Mean weight +/- SD of neonates was 2012.5 +/- 969 g. Application of
      lidocaine spray caused a significant reduction of mean intubation time among
      treatment group compared with placebo group (treatment: 15.03 +/- 2.2 seconds;
      placebo: 18.3 +/- 2.3 seconds; P < 0.0001). Mean blood pressure, heart rate and
      oxygen saturation rate, among neonates in treatment group was reduced after
      intubation compared with their relevant figures before intubation; however, their
      differences were not statistically significant except for mean oxygen saturation
      rate that was reduced significantly in placebo group. No side effects were
      observed during study. CONCLUSIONS: Though the current study revealed some
      promising results in the application of lidocaine spray during neonatal
      intubation without any considerable side effects; however, the current
      investigation could only be considered as a pilot study for further attempts in
      different locations with higher sample sizes and in different situations.

PMID- 26199689
TI  - Williams-Beuren Syndrome: A Case Confirmed by Array-CGH Method.

PMID- 26199690
TI  - Scrotal Exploration for Testicular Torsion and Testicular Appendage Torsion:
      Emergency and Reality.
AB  - BACKGROUND: Scrotal exploration is considered the procedure of choice for acute
      scrotum. OBJECTIVES: We evaluated the importance of early diagnosis and
      testicular salvage on the therapeutic outcomes of patients with pediatric
      testicular torsion (TT) and testicular appendage torsion (TAT) in our geographic
      area. PATIENTS AND METHODS: We performed a retrospective database analysis of
      patients who underwent emergency surgery for TT or TAT between January 1996 and
      June 2009. Patient history, physical examination findings, laboratory test
      results, color Doppler sonography (CDS) results, and surgical findings were
      reviewed. RESULTS: A total of 65 cases were included in our analysis. Forty-two
      cases were followed up for at least 3 months. Testicular tenderness was
      identified as the major clinical manifestation of TT, while only a few patients
      with TAT presented with swelling. CDS was an important diagnostic modality. The
      orchiectomy rate was 71% in the TT group. CONCLUSIONS: Cases of acute scrotum
      require attention in our area. Early diagnosis and scrotal exploration could
      salvage the testis or preserve normal function without the need for surgery.

PMID- 26199691
TI  - Amniotic Deformity, Adhesions, Mutilations (ADAM) Complex: A Frightful Condition.

PMID- 26199692
TI  - Effect of Metronidazole on Halitosis of 2 to 10 Years Old Children.
AB  - BACKGROUND: Regarding the fact that halitosis has social and personal aspects
      which can lead to social embarrassment and consequently low self-esteem and self
      confidence in subjects suffering from the problem, especially children, its
      proper treatment is an important issue. OBJECTIVES: The aim of this study was to
      evaluate the effect of metronidazole as a nonspecific antimicrobial agent in the
      treatment of halitosis in children. MATERIALS AND METHODS: In this study, 2-10
      years old children with oral halitosis were enrolled. Children without H. pylori
      infection and parasitic infection were randomized in two interventional and
      control groups. Metronidazole was given 5mg/kg/day for one week. Information
      regarding the demographic characteristics of studied population and halitosis
      (duration and time of day with more halitosis and its severity) before and after
      intervention was recorded using a questionnaire. RESULTS: 77 children with
      halitosis were studied in two interventional (40 children) and control (37
      children) groups. There was no significant difference between two groups before
      intervention. After intervention, halitosis improvement rate - according to the
      reports of mothers of studied children - was higher significantly in intervention
      group (P < 0.05). CONCLUSIONS: The results support the effectiveness of
      metronidazole in the treatment of halitosis. Moreover, it supports recent
      findings regarding the participation of specific bacteria specially unculturable
      ones in the pathogenesis of the disease.

PMID- 26199693
TI  - Evaluation of the Light-Cycler(r) SeptiFast Test in Newborns With Suspicion of
      Nosocomial Sepsis.
AB  - BACKGROUND: Nosocomial sepsis (NS) in newborns (NBs) is associated with high
      mortality rates and low microbial recovery rates. To overcome the latter problem,
      new techniques in molecular biology are being used. OBJECTIVES: To evaluate the
      diagnostic efficacy of SeptiFast test for the diagnosis of nosocomial sepsis in
      the newborn. MATERIALS AND METHODS: 86 blood specimens of NBs with suspected NS
      (NOSEP-1 Test > 8 points) were analyzed using Light Cycler SeptiFast (LC-SF) a
      real-time multiplex PCR instrument. The results were analyzed with the Roche
      SeptiFast Identification Software. Another blood sample was collected to carry
      out a blood culture (BC). RESULTS: Sensitivity (Sn) and specificity (Sp) of 0.69
      and 0.65 respectively, compared with blood culture (BC) were obtained for LC-SF.
      Kappa index concordance between LC-SF and BC was 0.21. Thirteen (15.11%) samples
      were BC positive and 34 (31.39%) were positive with LC-SF tests. CONCLUSIONS:
      Compared with BC, LC-SF allows the detection of a greater number of pathogenic
      species in a small blood sample (1 mL) with a shorter response time.

PMID- 26199694
TI  - Risperidone Versus Methylphenidate in Treatment of Preschool Children With
      Attention-Deficit Hyperactivity Disorder.
AB  - BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a common
      psychiatric diagnosis among preschool children. OBJECTIVES: The aim of this study
      was to examine the Risperidone treatment compared to Methylphenidate (MPH) in
      preschool children with ADHD. PATIENTS AND METHODS: Thirty three outpatient
      preschool children, aged 3-6 years, diagnosed with ADHD (The diagnosis of ADHD
      was established by two child and adolescent psychiatrists according to the DSM-IV
      TR criteria), participated in a 6-week, double-blind clinical trial with
      risperidone (0.5-1.5 mg/d) and methylphenidate (5-20 mg/d), in two divided doses.
      Treatment outcomes were assessed using the Parent ADHD Rating Scale and Conners
      Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4
      and 6 weeks after the medication started. Side effects were also rated by side
      effects questionnaire. RESULTS: There were no significant differences between the
      two protocols on the Parent ADHD Rating Scale scores (P > 0.05) and Parent
      Conners Rating Scale scores (P > 0.05). Both groups showed a significant
      improvement in ADHD symptoms over the 6 weeks of treatment for parent ADHD Rating
      Scale (P < 0.001) and Parent Conners Rating Scale (P < 0.001). The most common
      adverse effects seen with risperidone were daytime drowsiness and anorexia (20%),
      and with methylphenidate it was anorexia (55%). CONCLUSIONS: Results of this
      study show that risperidone may be effective and well tolerated for ADHD in
      preschool children, but more researches are needed to clarify the potential
      benefits and adverse effects in long term use and comorbid conditions.

PMID- 26199695
TI  - Different Kinds of Paraneoplastic Syndromes in Childhood Neuroblastoma.
AB  - BACKGROUND: Clinical presentations of paraneoplastic syndromes in neuroblastoma
      may multiply. Review of the clinical data and the literature on this syndrome may
      help in the diagnosis of neuroblastoma. OBJECTIVES: In order to make more
      accurate diagnosis, we reviewed the clinical data and the literature on this
      syndrome. PATIENTS AND METHODS: Between April 2007 and April 2012, 68 children
      were diagnosed with neuroblastoma or ganglioneuroblastoma in our institution, 9
      of which presented exclusively with paraneoplastic syndromes and were not treated
      with chemotherapy prior to diagnosis. After the diagnosis, all patients received
      chemotherapy and operation on NB97 protocol. RESULTS: Among 68 pediatric patients
      with neuroblastoma or ganglioneuroblastoma, 4 (5.9%) patients suffered from
      neurological complications at diagnosis, 2 (2.9%) patients had digestive tract
      disorders, 2 (2.9%) patients had immune diseases, and 1 (1.5%) suffered from
      hematological disorder (without bone marrow involvement). All paraneoplastic
      syndrome patients achieved complete remission on paraneoplastic syndrome before
      completion of chemotherapy. CONCLUSIONS: Neuroblastoma may present with a range
      of non-specific neurologic symptoms in addition to the well-known opsoclonus
      myoclonus syndrome and cerebellar ataxia. In any case, the presence of
      unexplained neurologic manifestations and other common clinical presentations
      such as rash, constipation, diarrhea, and especially immune disorders in an
      otherwise healthy child had raised the possibility of paraneoplastic syndrome due
      to the presence of an undiagnosed tumor.

PMID- 26199696
TI  - Association of TNF-alpha Gene Variants With Clinical Manifestation of Cystic
      Fibrosis Patients of Iranian Azeri Turkish Ethnicity.
AB  - BACKGROUND: Cystic fibrosis (CF), a life-limiting autosomal recessive disorder,
      is considered a monogenic disease that is caused by mutations in the cystic
      fibrosis transmembrane conductance regulator (CFTR) gene. According to several
      studies, mutation analysis of the cystic fibrosis transmembrane conductance
      regulator (CFTR) gene alone is insufficient to predict the phenotypic
      manifestations observed in cystic fibrosis (CF) patients. In addition, some
      patients with a milder CF phenotype do not carry any pathogenic mutation. Tumor
      Necrosis Factor-alpha (TNF-alpha) contributes to the pathophysiology of CF by
      causing cachexia. There is a reverse association between TNF-alpha concentration
      in patient's sputum and their pulmonary function. OBJECTIVES: To assess the
      effect of non-CFTR genes on the clinical phenotype of CF, two polymorphic sites (
      1031T/C and -308G/A) of the TNF-alpha gene, as a modifier, were studied. PATIENTS
      AND METHODS: Focusing on the lung and gastrointestinal involvement as well as the
      poor growth, we first investigated the role of TNF-alpha gene in the clinical
      manifestation of CF. Furthermore, based on the hypothesis that the cumulative
      effect of specific alleles of multiple CF modifier genes, such as TNF-alpha, may
      create the final phenotype, we also investigated the potential role of TNF-alpha
      in non-classic CF patients without a known pathogenic mutation. In all, 80 CF
      patients and 157 healthy control subjects of Azeri Turkish ethnicity were studied
      by the PCR-RFLP method. The chi-square test with Yates' correction and Fisher's
      exact test were used for statistical analysis. RESULTS: The allele and genotype
      distribution of the investigated polymorphisms, and their associated haplotypes
      were similar in all groups. CONCLUSIONS: There was no evidence that supported the
      association of TNF-alpha gene polymorphisms with non-classic CF disease or the
      clinical presentation of classic CF.

PMID- 26199697
TI  - Pediatric Nurses' Information and Applications Related To Ethical Codes.
AB  - BACKGROUND: Ethics is defined as the entirety of moral principles that form the
      basis of individuals' behavior; it can also be defined as "moral theory" or
      "theoretical ethics". OBJECTIVES: To determinate information and applications
      related to ethical codes of pediatric nurses. PATIENTS AND METHODS: Participants
      were nurses attending the Neonatal Intensive Care Unit Nursing Course and the
      Pediatric Nursing Course conducted in Istanbul between September 2011 and
      December 2012. A total of nurses attending the courses at the specified dates and
      who agreed to participate in the study were included in the analysis. Data were
      collected through a questionnaire that we developed in accordance with current
      literature on nursing ethics. RESULTS: 140 nurses participated in this study.
      Information and applications were related to ethical codes of nurses including
      four categories; autonomy, beneficence, nonmaleficence, justice. The principle of
      confidentiality/keeping secrets. Exactly 64.3% of nurses reported having heard of
      nursing ethical codes. The best-known ethical code was the principle of justice.
      Furthermore, while the rates were generally low, some nurses engaged in unethical
      practices such as patient discrimination and prioritizing acquaintances.
      CONCLUSIONS: We conclude that most nurses working in pediatric clinics act in
      compliance with ethical codes. We also found that the majority of nurses wanted
      to learn about ethical codes. For this reason, we recommended that nurses working
      in clinics and future nurses in training be informed of the appropriate ethical
      behavior and codes.

PMID- 26199698
TI  - The Role of Lung Ultrasound in Diagnosis of Respiratory Distress Syndrome in
      Newborn Infants.
AB  - BACKGROUND: Respiratory distress syndrome (RDS) is one of the most common causes
      of neonatal respiratory failure and mortality. The risk of developing RDS
      decreases with both increasing gestational age and birth weight. OBJECTIVES: The
      aim of this study was to evaluate the value of lung ultrasound in the diagnosis
      of respiratory distress syndrome (RDS) in newborn infants. MATERIALS AND METHODS:
      From March 2012 to May 2013, 100 newborn infants were divided into two groups:
      RDS group (50 cases) and control group (50 cases). According to the findings of
      chest x-ray, there were 10 cases of grade II RDS, 15 grade III cases, and 25
      grade IV cases in RDS group. Lung ultrasound was performed at bedside by a single
      expert. The ultrasound indexes observed in this study included pleural line, A
      line, B-line, lung consolidation, air bronchograms, bilateral white lung,
      interstitial syndrome, lung sliding, lung pulse etc. RESULTS: In all of the
      infants with RDS, lung ultrasound consistently showed generalized consolidation
      with air bronchograms, bilateral white lung or alveolar-interstitial syndrome,
      pleural line abnormalities, A-line disappearance, pleural effusion, lung pulse,
      etc. The simultaneous demonstration of lung consolidation, pleural line
      abnormalities and bilateral white lung, or lung consolidation, pleural line
      abnormalities and A-line disappearance co-exists with a sensitivity and
      specificity of 100%. Besides, the sensitivity was 80% and specificity 100% of
      lung pulse for the diagnosis of neonatal RDS. CONCLUSIONS: This study indicates
      that using an ultrasound to diagnose neonatal RDS is accurate and reliable too. A
      lung ultrasound has many advantages over other techniques. Ultrasound is non
      ionizing, low-cost, easy to operate, and can be performed at bedside, making this
      technique ideal for use in NICU.

PMID- 26199699
TI  - Procalcitonin Biomarker Kinetics to Predict Multiorgan Dysfunction Syndrome in
      Children With Sepsis and Systemic Inflammatory Response Syndrome.
AB  - BACKGROUND: Procalcitonin (PCT) kinetics is a good prognosis marker in infectious
      diseases, but few studies of children sepsis have been performed. OBJECTIVES: The
      aim of our study was to examine kinetics of procalcitonin, to evaluate its
      relationship with severity and to analyze its usefulness in the prediction of
      multiorgan dysfunction syndrome (MODS). PATIENTS AND METHODS: Prospective
      observational study in an 8-bed pediatric intensive care unit of a university
      hospital. Sixty-two children aged 0-19 years with systemic inflammatory response
      syndrome or septic states. The degree of severity was evaluated according
      pediatric logistic organ dysfunction (PELOD) score. Blood tests to determine
      levels of PCT were taken if the patients had the criteria of systemic
      inflammatory response syndrome or sepsis. The serum to determine levels of PCT in
      control group has been taken from patients undergoing elective surgery. RESULTS:
      Higher values of PCT were identified in patients with PELOD score 12 and more
      compared to those with PELOD < 12 (P = 0.016). Similarly, higher PCT values were
      found in patients who developed MODS in contrast to those without MODS (P =
      0.011). According to ROC analysis cut-off value of 4.05 ng/mL was found to best
      discriminate patients with PELOD < 12 and PELOD >= 12 with AUC = 0.675 (P =
      0.035). Effect of procalcitonin levels on mortality was not demonstrated.
      CONCLUSIONS: Levels of procalcitonin from day 1 to day 5 are related to the
      severity and multiorgan dysfunction syndrome in children.

PMID- 26199700
TI  - Short Term Outcome of Neonates Born With Abnormal Umbilical Cord Arterial Blood
      Gases.
AB  - BACKGROUND: Umbilical arterial blood gas (UABG) analysis is more objective than
      other methods for predicting neonatal outcome. Acidemic neonates may be at risk
      for unfavorable outcome after birth, but all neonates with abnormal arterial
      blood gas (ABG) analysis do not always have poor outcome. OBJECTIVES: This study
      was carried out to determine the short term outcome of the neonates born with an
      abnormal ABG. PATIENTS AND METHODS: In a cohort prospective study 120 high risk
      mother-neonate pairs were enrolled and UABG was taken immediately after birth.
      All neonates with an umbilical cord pH less than 7.2 were considered as case
      group and more than 7.2 as controls. Outcomes like need to resuscitation,
      admission to newborn services and/or NICU), seizure occurrence, hypoxic ischemic
      encephalopathy (HIE), delayed initiation of oral feeding and length of hospital
      stay were recorded and compared between the two groups. P value less than 0.05
      was considered as being significant. RESULTS: Comparison of short term outcomes
      between normal and abnormal ABG groups were as the fallowing: need for advanced
      resuscitation 4 vs. 0 (P = 0.001), NICU admission 16 vs. 4 (P = 0.001),
      convulsion 2 vs. 0 (P = 0.496), HIE 17 vs. 4 (P = 0.002), delay to start oral
      feeding 16 vs. 4 (P = 0.001), mean hospital stay 4 vs. 3 days (P = 0.001). None
      of the neonates died in study groups. CONCLUSIONS: An umbilical cord PH less than
      7.2 immediately after birth can be used as a prognostic factor for unfavorable
      short term outcome in newborns.

PMID- 26199701
TI  - Noninvasive Evaluation of Myocardial Systolic Dysfunction in the Early Stage of
      Kawasaki Disease: A Speckle-Tracking Echocardiography Study.
AB  - BACKGROUND: Evaluation of myocardial function by speckle-tracking
      echocardiography is a new method for the early diagnosis of systolic dysfunction.
      OBJECTIVES: We aimed to determine myocardial speckle-tracking echocardiography
      indices in Kawasaki Disease (KD) patients and compare them with the same indices
      in control subjects. PATIENTS AND METHODS: Thirty-two patients (65.5% males) with
      KD and 19 control subjects with normal echocardiography participated in this
      study. After their demographic characteristics and clinical findings were
      recorded, all the participants underwent transthoracic echocardiography. Strain
      (S), Strain Rate (SR), Time to Peak Strain (TPS), and Strain Rate (TPSR),
      longitudinal velocity and view point velocity images in the two, three, and four
      chamber views were semi-automatically obtained via speckle-tracking
      echocardiography. RESULTS: Among the patients, Twenty-four cases (75%) were
      younger than 4 years. Mean global S and SR was significantly reduced in the KD
      patients compared to controls (17.03 +/- 1.28 vs. 20.22 +/- 2.14% and 1.66 +/-
      0.16 vs. 1.97 +/- 0.25 1/second, respectively), while there were no significant
      differences regarding mean TPS, TPSR, longitudinal velocity and view point
      velocity. Using repeated measure of analysis of variances, we observed that S and
      SR decreased from base to apical level in both groups. The change in the pattern
      of age adjusted mean S and SR across levels was significantly different between
      the groups (P < 0.001 for both parameters). CONCLUSIONS: We showed changes in S
      and SR assessed in KD patients versus control subjects in the acute phase of KD.
      However, we suggest that further studies be undertaken to compare S and SR in the
      acute phase and thereafter in KD patients.

PMID- 26199702
TI  - West Nile Encephalitis and Its Characteristics in Childhood.

PMID- 26199703
TI  - Changes of Total Plasma Triglycerides in Neonates Treated With Intralipid: A
      Pilot Study.

PMID- 26199704
TI  - Psychological Aspects in Children and Adolescents With Major Thalassemia: A Case
      Control Study.
AB  - BACKGROUND: Thalassemia is an inherited blood disease. It is a serious public
      health problem throughout the Mediterranean region, the Middle East and the
      Indian subcontinent, as well as in Southeast Asia. OBJECTIVES: Thalassemia is an
      inherited blood disease. It is a serious public health problem. In this study we
      assessed psychological aspects in Iranian children and adolescents with
      thalassemia major. PATIENTS AND METHODS: In this case-control study sixty healthy
      subjects aged 7-18 years and Sixty Patients with confirmed diagnosis of major
      thalassemia were enrolled. After obtaining informed consent from parents of all
      participating thalassemia patients and healthycontrols, we assessed psychological
      aspects and quality of life by Pediatric Quality of LifeTM (PedsQLTM), Strengths
      and Difficulties Questionnaires (SDQ), State and Trait Anxiety, Children's
      Depression Inventory (CDI). RESULTS: The results of this study indicate that
      there are significant changes in depression, anxiety, QOL and behavioral
      screening between children with thalassemia major compared with healthy subjects
      by means of both parents and children reports. According to the results, children
      with thalassemia major have more psychological problems than healthy ones.
      Patients with thalassemia have a lower QOL than their peers (P = 0.001), the rate
      of depression is higher in this group (P = 0.015), Also behavioral problems in
      these children are more than healthy subjects (P = 0.009). CONCLUSIONS: We
      recommend appropriate treatment and counseling procedures in addition to specific
      treatment of thalassemia. According to the results we suggest to establish
      pediatric psychiatric clinics beside thalassemic clinics to cure psychological
      aspects of the disease.

PMID- 26199705
TI  - Secondary Hemophagocytosis in Propionic Acidemia.

PMID- 26199706
TI  - Idiopathic Orbital Myositis in a 9-Year-Old Girl: A Case Report.

PMID- 26199707
TI  - Prevalence of General and Abdominal Obesity in a Nationally Representative Sample
      of Iranian Children and Adolescents: The CASPIAN-IV Study.
AB  - BACKGROUND: Pediatric obesity is one of the predisposing risk factors for many
      non-communicable diseases. OBJECTIVES: The purpose of this study was to estimate
      the national prevalence of general and abdominal obesity among Iranian children
      and adolescents. PATIENTS AND METHODS: This cross-sectional nation-wide study was
      performed in 30 provinces in Iran among 14880 school students aged 6 - 18 years,
      selected by multistage random cluster sampling. The World Health Organization
      growth curve was used to categorize Body Mass Index (BMI). Obesity was defined as
      BMI equal to or higher than the age- and gender-specific 95(th) percentile;
      abdominal obesity was considered as waist-to-height ratio of more than 0.5.
      RESULTS: Data of 13486 out of 14880 invited students were complete (response rate
      of 90.6%). They consisted of 6543 girls and 75.6% urban residents, and had a mean
      age of 12.45 (95% CI: 12.40 - 12.51) years. The prevalence rate of general and
      abdominal obesity was 11.89% (13.58% of boys vs. 10.15% of girls) and 19.12%
      (20.41% of boys vs. 17.79% of girls), respectively. The highest frequency of
      obesity was found in the middle school students (13.87% general and 20.84%
      abdominal obesity). The highest prevalence of general obesity was found in
      Boushehr (19%) followed by Guilan and Mazandaran (18.3%, 18.3%), while the lowest
      prevalence was observed in Hormozgan (2.6%). The highest frequency of abdominal
      obesity was found in Mazandaran (30.2%), Ardabil (29.2%) and Tehran (27.9%).
      Provinces such as Sistan-Baloochestan (8.4%), Hormozagan (7.4%), and Kerman
      (11.4%) had the lowest prevalence of abdominal obesity. The Southern and South
      Eastern provinces had the lowest prevalence of general obesity (2.6% and 5.6%)
      and abdominal obesity (7.4% and 8.8%). Moreover, the highest prevalence of
      obesity was found in North and North West Iran by maximum frequency of 18.3%
      general obesity and 30.2% of abdominal obesity. CONCLUSIONS: The results showed a
      high prevalence of general and abdominal obesity among boys living in the
      Northern provinces of Iran. The present study provides insights that policy
      makers should consider action-oriented interventions for prevention and control
      of childhood obesity at national and sub-national level.

PMID- 26199708
TI  - Effect of Playing Interactive Computer Game on Distress of Insulin Injection
      Among Type 1 Diabetic Children.
AB  - BACKGROUND: Diabetic children and their families experience high level stress
      because of daily insulin injection. OBJECTIVES: This study was conducted to
      investigate the impact of an interactive computer game on behavioral distress due
      to insulin injection among diabetic children. PATIENTS AND METHODS: In this
      clinical trial, thirty children (3-12 years) with type 1 diabetes who needed
      daily insulin injection were recruited and allocated randomly into two groups.
      Children in intervention groups received an interactive computer game and asked
      to play at home for a week. No special intervention was done for control group.
      The behavioral distress of groups was assessed before, during and after the
      intervention by Observational Scale of Behavioral Distress-Revised (OSBD-R).
      RESULTS: Repeated measure ANOVA test showed no significantly difference of OSBD-R
      over time for control group (P = 0.08), but this changes is signification in the
      study group (P = 0.001). Comparison mean score of distress were significantly
      different between two groups (P = 0.03). CONCLUSIONS: According to the findings,
      playing interactive computer game can decrease behavioral distress induced by
      insulin injection in type 1 diabetic children. It seems this game can be
      beneficial to be used alongside other interventions.

PMID- 26199709
TI  - The Effect of Stress Management Program Using Cognitive Behavior Approach on
      Mental Health of the Mothers of the Children With Attention Deficit Hyperactivity
      Disorder.
AB  - BACKGROUND: Attention deficit hyperactivity disorder is one of the most common
      psychiatric disorders in children. OBJECTIVES: The study aimed to evaluate the
      effectiveness of stress management program using cognitive behavior approach on
      mental health of the mothers of the children with attention deficit hyperactivity
      disorder. PATIENTS AND METHODS: In this interventional study, 90 mothers of the
      children with attention deficit hyperactivity disorder were randomly allocated
      into three intervention, placebo, and control groups. The general health
      questionnaire was used to measure mental health. Besides, stress was assessed
      through the depression-anxiety-stress scale. The two instruments were completed
      at baseline, immediately after, and one month after the intervention by the
      mothers. Afterwards, within group comparisons were made using one-sample repeated
      measurement ANOVA. One-way ANOVA was used for inter group comparisons. Mothers in
      the placebo group only participated in meetings to talk and express feelings
      without receiving any interventions. RESULTS: At the baseline, no significant
      difference was found among the three groups regarding the means of stress,
      anxiety, depression, and mental health. However, a significant difference was
      observed in the mean score of stress immediately after the intervention (P =
      0.033). The results also showed a significant difference among the three groups
      regarding the mean score of mental health (P < 0.001). One month after the
      intervention, the mean difference of mental health score remained significant
      only in the intervention group (P < 0.001). CONCLUSIONS: The study findings
      confirmed the effectiveness of stress management program utilizing cognitive
      behavior approach in mental health of the mothers of the children with attention
      deficit hyperactivity disorder.

PMID- 26199710
TI  - Efficacy and Safety of Orally Administered Intravenous Midazolam Versus a
      Commercially Prepared Syrup.
AB  - BACKGROUND: Among different categories of sedative agents, benzodiazepines have
      been prescribed for more than three decades to patients of all ages. The
      effective and predictable sedative and amnestic effects of benzodiazepines
      support their use in pediatric patients. Midazolam is one of the most extensively
      used benzodiazepines in this age group. Oral form of drug is the best accepted
      route of administration in children. OBJECTIVES: The purpose of this study was to
      compare the efficacy and safety of a commercially midazolam syrup versus orally
      administered IV midazolam in uncooperative dental patients. Second objective was
      to determine whether differences concerning sedation success can be explained by
      child's behavioral problems and dental fear. PATIENTS AND METHODS: Eighty eight
      uncooperative dental patients (Frankl Scales 1,2) aged 3 to 6 years, and ASA I
      participated in this double blind, parallel randomized, controlled clinical
      trial. Midazolam was administered in a dose of 0.5 mg/kg for children under the
      age 5 and 0.2 mg/kg in patients over 5 years of age. Physiologic parameters
      including heart rate, respiratory rate, oxygen saturation and blood pressure were
      recorded. Behavior assessment was conducted throughout the course of treatment
      using Houpt Sedation Rating Scale and at critical moments of treatment (injection
      and cavity preparation) by North Carolina Scale. Dental fear and behavioral
      problems were evaluated using Child Fear Schedule Survey-Dental Subscale (CFSS
      DS), and Strength and Difficulties Questionnaire (SDQ). Independent t-test, Chi
      Square, and Pearson correlation were used for statistical analysis. RESULTS:
      Acceptable overall sedation ratings were observed in 90% and 86% of syrup and
      IV/Oral group respectively; Chi-Square P = 0.5. Other domains of Houpt Scale
      including: sleep, crying and movement were also not significantly different
      between groups. Physiological parameters remained in normal limits during study
      without significant difference between groups. CONCLUSIONS: "Orally administered
      IV midazolam" preparation can be used as an alternative for commercially
      midazolam syrup.

PMID- 26199711
TI  - The Effects of Instrumental Touching on Infant Pain Perception and the Effects of
      Eutectic Mixture of Local Anesthetics (EMLA) on the Reduction of Pain.
AB  - BACKGROUND: Premature infants, who have to spend the first week of their lives in
      neonatal intensive care units (NICUs), experience pain and stress in numerous
      cases, and they are exposed to many invasive interventions. The studies have
      shown that uncontrolled pain experienced during early life has negative and long
      term side effects, such as distress, and such experiences negatively affect the
      development of the central nervous system. OBJECTIVES: The purpose of the study
      was to examine the effects of touching on infant pain perception and the effects
      of eutectic mixture of local anesthetic (EMLA) on the reduction of pain. PATIENTS
      AND METHODS: Data for the study were collected between March and August 2012 from
      the neonatal clinic of a university hospital located in eastern Turkey. The
      population of the study consisted of premature infants who were undergoing
      treatment, completed the first month and who were approved for Hepatitis B
      vaccine. The study consisted of two experimental groups and one control group.
      Information forms, intervention follow-up forms, and Premature Infant Pain
      Profile (PIPP) were used to collect the data. EMLA cream was applied on the
      vastus lateralis muscles of the first experimental group before the vaccination.
      The second experimental group was vaccinated by imitation (placebo), without a
      needle tip or medicine. Vaccination was carried out using instrumental touch in
      this group. A routine vaccination was applied in the control group. RESULTS: Mean
      pain scores of the group to which EMLA was applied were lower in a statistically
      significant way (P < 0.05) compared to the pain scores of the other groups.
      Moreover, it was determined that even though invasive intervention was not
      applied to the newborns, the touching caused them to feel pain just as in the
      placebo group (P < 0.005). CONCLUSIONS: The results demonstrated that EMLA was an
      effective method for reducing pain in premature newborns, and the use of
      instrumental touch for invasive intervention stimulated the pain perception in
      the newborns.

PMID- 26199712
TI  - Cyanosis As a Signal of Perinatal Stroke: Findings at Ultrasound and MRI.

PMID- 26199713
TI  - The Effects of Non-Nutritive Sucking and Pre-Feeding Oral Stimulation on Time to
      Achieve Independent Oral Feeding for Preterm Infants.
AB  - BACKGROUND: The survival rates of preterm infants has increased over the last
      years, but oral feeding difficulties are the most common problems encountered by
      them. OBJECTIVES: This study aimed at comparing the effects of non-nutritive
      sucking (NNS) and pre-feeding oral stimulation on feeding skills, length of
      hospital stay and weight gain of 26-32 weeks gestational age preterm infants in
      NICU, to determine the more effective intervention. PATIENTS AND METHODS: Thirty
      two preterm infants were assigned randomly into three groups. One intervention
      group received pre-feeding oral stimulation program and the other received non
      nutritive sucking stimulation, while the control group received a sham
      intervention. Gestational age of infants was calculated during 1, 4 and 8 oral
      feeding and discharge time from NICU. The infants' weights were measured weekly
      from birth and at discharge time. RESULTS: Mean gestational age on 8 time oral
      feeding per day, in 3 groups was not significant (P = 0.282). Although NNS and
      pre-feeding oral stimulation groups has fulfilled this criterion 7.55 and 6.07
      days sooner than the control group, respectively (a result which is of great
      clinical and economic importance), but the difference did not reach statistical
      significance. Weight gaining at discharge time in NNS group was significantly
      higher than control and pre-feeding oral stimulation groups (P < 0.05).
      CONCLUSIONS: This study revealed that pre-feeding oral stimulation and NNS
      programs both were effective on oral feeding skills and weight gaining of the
      immature newborns. Yet, it seems that NNS program was more effective than pre
      feeding oral stimulation on weight gaining.

PMID- 26199715
TI  - Editorial.

PMID- 26199714
TI  - A longitudinal twin study of the association between childhood autistic traits
      and psychotic experiences in adolescence.
AB  - BACKGROUND: This twin study investigated whether autistic traits during childhood
      were associated with adolescent psychotic experiences. METHODS: Data were
      collected from a community sample of approximately 5000 twin pairs, which
      included 32 individuals with diagnosed autism spectrum conditions (ASC). Parents
      rated autistic traits in the twins at four points between ages 8-16 years.
      Positive, negative, and cognitive psychotic experiences were assessed at age 16
      years using self- and parent-report scales. Longitudinal twin analyses tested the
      associations between these measures. RESULTS: Autistic traits correlated weakly
      or nonsignificantly with positive psychotic experiences (paranoia,
      hallucinations, and grandiosity), and modestly with cognitive psychotic
      experiences (cognitive disorganisation). Higher correlations were observed for
      parent-rated negative symptoms and self-reported anhedonia, although the
      proportion of variance in both accounted for by autistic traits was low (10 and
      31 %, respectively). The majority of the genetic influences on negative symptoms
      and anhedonia were independent of autistic traits. Additionally, individuals with
      ASC displayed significantly more negative symptoms, anhedonia, and cognitive
      disorganisation than controls. CONCLUSIONS: Autistic traits do not appear to be
      strongly associated with psychotic experiences in adolescence; associations were
      also largely restricted to negative symptoms. Of note, the degree to which the
      genetic and environmental causes of autistic traits influenced psychotic
      experiences was limited. These findings thus support a phenotypic and etiological
      distinction between autistic traits and psychotic experiences.

PMID- 26199716
TI  - An evaluation of subjective experiences, effects and overall satisfaction with
      clozapine treatment in a UK forensic service.
AB  - OBJECTIVES: Patients prescribed clozapine were surveyed to assess (a) the
      effects, both positive and adverse, and overall satisfaction with clozapine in
      comparison to previously prescribed antipsychotics and (b) the relative
      significance of effects experienced, both positive and adverse, in terms of
      impact on subjective well-being. METHODS: A total of 56 male patients prescribed
      clozapine at a forensic psychiatric hospital were surveyed using a 27-item
      questionnaire. All patients had been prescribed clozapine for a minimum of 3
      months. Respondents were asked to rate effects and satisfaction with clozapine
      treatment in comparison with previously prescribed antipsychotic medication on a
      five-point scale. Respondents were also asked to rate effects experienced with
      clozapine treatment in terms of impact on subjective well-being on a five-point
      scale. RESULTS: A total of 89% of respondents reported greater satisfaction with
      clozapine than with previously prescribed antipsychotic medication. A majority of
      patients reported positive effects in terms of an improvement in their quality of
      life (68%) and social abilities (52%) with clozapine in comparison with
      previously prescribed antipsychotics. Nocturnal hypersalivation (84%) and weight
      gain (57%) were the most common adverse effects. Hedonic responses were assessed
      for each effect in order to determine the associated subjective experiences. The
      most positive hedonic responses were for quality of life, mood and alertness. In
      terms of adverse impact on subjective well-being, nocturnal hypersalivation
      ranked highest. CONCLUSIONS: Patients in a UK forensic sample are largely
      satisfied with clozapine treatment. The subjective effects of clozapine treatment
      should be taken into account by clinicians when assessing response. This may
      provide an opportunity to highlight the positive changes and prioritize
      management of the most undesirable adverse effects, which is likely to promote
      compliance and improve longer term treatment outcomes.

PMID- 26199717
TI  - Five-year patient outcomes with risperidone long-acting injection or oral
      aripiprazole.
AB  - BACKGROUND: This study examined 5-year outcomes of patients prescribed
      risperidone long-acting injection (RLAI) or aripiprazole in a clinical setting,
      using treatment discontinuation as a measure of effectiveness. METHOD: Patients
      who received RLAI or aripiprazole in the 18 months following their respective UK
      launches were included. Two-year outcome data were previously reported for these
      cohorts; this study reported an additional 3 years of follow up for each group.
      Data were collected from pharmacy records and by retrospective case note review.
      Patients were classified as continuers or discontinuers at 5 years and reasons
      for treatment discontinuation noted. RESULTS: The number of patients remaining on
      treatment at 2 years (and included in this study) was 28/84 and 27/92 for RLAI
      and aripiprazole respectively. Two patients treated with RLAI and three treated
      with aripiprazole were lost to follow up. Therefore, 5-year outcome data were
      available for 50 patients. Fifteen patients from each group were continuers at 5
      years. Of these, four receiving RLAI and three receiving aripiprazole were
      coprescribed other antipsychotics at study endpoint. Reasons for discontinuation
      of RLAI and aripiprazole respectively were lack of effect (n = 4; n = 4), adverse
      effects (n = 3; n = 1), noncompliance or patient choice (n = 2; n = 4) and
      patient death (n = 2; n = 0). CONCLUSION: There was no significant difference
      between the proportions of patients continuing RLAI or aripiprazole for 5 years.
      Continuation rates were relatively low (18% and 16% of the original RLAI and
      aripiprazole cohorts respectively), whilst coprescription of other antipsychotics
      at endpoint was relatively common. Lack of effectiveness was the most common
      reason for discontinuation of both compounds. These findings suggested that
      clinical effectiveness was somewhat disappointing, although the long period of
      follow up and number of patients previously treated with clozapine in the
      original cohorts were confounding factors.

PMID- 26199718
TI  - Effect of comedication of bupropion and other antidepressants on body mass index.
AB  - BACKGROUND: Weight gain as an adverse effect of monotherapy of antidepressant has
      been well-studied. The effects of augmentation therapy involving multiple
      antidepressants, on weight changes needs to be adequately addressed. OBJECTIVE:
      To study the co-medication effects of bupropion in combination with six
      individual antidepressants on body mass index (BMI) using EMR based data
      analysis. METHODS: Allscripts data warehouse was used to identify patients on
      monotherapy of five selective serotonin reuptake inhibitor (SSRI) drugs,
      escitalopram, sertraline, citalopram, paroxetine, fluoxetine, one selective
      norepinephrine reuptake inhibitor (SNRI) duloxetine and the aminoketone,
      bupropion for at least 180 days. We also identified patients on co-medication of
      SSRI/SNRI drugs with bupropion. Six ANCOVA models were built to compare the short
      term effects on BMI, among monotherapy and co-medication groups. The patients'
      clinical conditions and demographics were included to account for confounding
      effects. RESULTS: Monotherapy of all the SSRI/SNRI drugs showed significant
      weight increase, consistent with that of previous studies. The co-medication of
      bupropion and escitalopram showed a significantly higher increase in BMI than
      monotherapy (P = 0.0102). The increase in BMI in the other five co-medication
      groups was not significantly different from their respective monotherapy groups.
      CONCLUSION: Our study reports an adverse weight gain on co-medication of
      escitalopram and bupropion, which warrants further validation studies.
      Considering co-medication effects of antidepressants on weight is important to
      design robust depression treatment plans.

PMID- 26199719
TI  - Quetiapine versus aripiprazole in the management of schizophrenia.
AB  - OBJECTIVES: Current evidence supports the use of various second-generation
      antipsychotics for pharmacotherapy of schizophrenia. While in a systematic
      review, generally no difference in efficacy was found between atypical
      antipsychotics, other studies have found quetiapine less effective than
      aripiprazole. This article reviews the efficacy and tolerability of aripiprazole
      versus quetiapine in the context of recommended management strategies for
      schizophrenia. METHOD: Fifty female inpatients, meeting the diagnosis of
      schizophrenia, were randomly entered into two groups (n = 25 in each group) to
      participate in a 12-week, double-blind study for random assignment to quetiapine
      or aripiprazole. The primary outcome measures were Scale for Assessment of
      Positive Symptoms and Scale for Assessment of Negative Symptoms. The schedule for
      Assessment of Insight (SAI), Clinical Global Impressions Severity Scale (CGI-S)
      and the Simpson Angus Scale (SAS) were also used as secondary measures. RESULTS:
      Both quetiapine and aripiprazole showed significant effectiveness in the
      improvement of positive symptoms. The effectiveness for negative symptoms was
      also noteworthy with both drugs, although not to a significant level during this
      study. In addition, significant improvement was found on assessment with CGI-S
      and SAI for quetiapine and aripiprazole. SAS did not show any important increment
      in extrapyramidal side effects at the end of the examination. CONCLUSION:
      According to the findings, quetiapine and aripiprazole had similar effectiveness
      and tolerability with respect to management of schizophrenia.

PMID- 26199720
TI  - Revisiting the 'self-medication' hypothesis in light of the new data linking low
      striatal dopamine to comorbid addictive behavior.
AB  - Persons with schizophrenia are at a high risk, almost 4.6 times more likely, of
      having drug abuse problems than persons without psychiatric illness. Among the
      influential proposals to explain such a high comorbidity rate, the 'self
      medication hypothesis' proposed that persons with schizophrenia take to drugs in
      an effort to cope with the illness and medication side effects. In support of the
      self-medication hypothesis, data from our earlier clinical study confirmed the
      strong association between neuroleptic dysphoria and negative subjective
      responses and comorbid drug abuse. Though dopamine has been consistently
      suspected as one of the major culprits for the development of neuroleptic
      dysphoria, it is only recently our neuroimaging studies correlated the emergence
      of neuroleptic dysphoria to the low level of striatal dopamine functioning.
      Similarly, more evidence has recently emerged linking low striatal dopamine with
      the development of vulnerability for drug addictive states in schizophrenia. The
      convergence of evidence from both the dysphoria and comorbidity research,
      implicating the role of low striatal dopamine in both conditions, has led us to
      propose that the person with schizophrenia who develops dysphoria and comorbid
      addictive disorder is likely to be one and the same. 

PMID- 26199721
TI  - MDMA for the treatment of mood disorder: all talk no substance?
AB  - BACKGROUND: Unipolar depression is the third highest contributor to the global
      burden of disease, yet current pharmacotherapies typically take about 6 weeks to
      have an effect. A rapid-onset agent is an attractive prospect, not only to
      alleviate symptoms before first-line antidepressants display therapeutic action,
      but as a further treatment option in nonresponsive cases. It has been suggested
      that 3,4-methylene-dioxymethamphetamine (MDMA) could play a part in the treatment
      of depression, either as a rapid-onset pharmacological agent or as an adjunct to
      psychotherapy. Whilst these hypotheses are in keeping with the monoamine theory
      of depression and the principles surrounding psychotherapy, explicit experimental
      evidence of an antidepressant effect of MDMA has rarely been established. AIMS:
      To address the hypothesis surrounding MDMA as a rapid-onset antidepressant by
      examining pharmacological, psychological and behavioural studies. We consider
      whether this therapy could be safe by looking at the translation of neurotoxicity
      data from animals to humans. METHOD: A literature review of the evidence
      supporting this hypothesis was performed. CONCLUSIONS: The pharmacology of MDMA
      offers a promising target as a rapid-onset agent and MDMA is currently being
      investigated for use in psychotherapy in anxiety disorders; translation from
      these studies for use in depression may be possible. However, experimental
      evidence and safety analysis are insufficient to confirm or reject this theory at
      present.

PMID- 26199722
TI  - A moral dilemma argument against clinical trials of incentives for kidney
      donation.
AB  - Commercial transplant tourism results in significant harm to both kidney donors
      and recipients. However, proponents of incentives for kidney donation assert that
      proper oversight of the process prevents these harms and also that transplant
      numbers can be safely increased so that the moral burden of poor end-stage kidney
      disease outcomes can be alleviated. In a moral dilemma analysis, the principle of
      preventing donor harm can be dissociated from the principles of providing
      benefits to the recipient and to society. It is plausible that an incentivized
      donor is fundamentally different from an uncompensated donor. Incentivized donors
      can experience harms unrelated to lack of regulation because their
      characteristics are determined by the incentive superimposed upon a poverty
      circumstance. Moreover, creating a system of incentivized donation without
      established national registries for capturing all long-term donor outcomes would
      be morally inconsistent, since without prior demonstration that donor outcomes
      are not income or wealth-dependent, a population of incentivized donors cannot be
      morally created in a clinical trial. Socioeconomic factors adversely affect
      outcome in other surgical populations, and interventions on income or wealth in
      these populations have not been studied. Coercion will be increased in families
      not affected by kidney disease, where knowledge of a new income source and not of
      a potential recipient is the incentive. In the case of elective surgery such as
      kidney donation, donor non-maleficence trumps donor autonomy, recipient
      beneficence, and beneficence to society when there is a conflict among these
      principles. Yet, we are still faced with the total moral burden of end-stage
      kidney disease, which belongs to the society that cannot provide enough donor
      kidneys. Acting according to one arm of the dilemma to prevent donor harm does
      not erase obligations towards the other, to provide recipient benefit. To resolve
      the moral burden, as moral agents, we must rearrange our institutions by
      increasing available donor organs from other sources. The shortage of donor
      kidneys creates a moral burden for society, but incentives for donation will only
      increase the total moral burden of end-stage kidney disease. 

PMID- 26199723
TI  - What motivates antibiotic dispensing in accredited drug dispensing outlets in
      Tanzania? A qualitative study.
AB  - BACKGROUND: Tanzania introduced the accredited drug dispensing outlet (ADDO)
      program more than a decade ago. Previous evaluations have generally shown that
      ADDOs meet defined standards of practice better than non-accredited outlets.
      However, ADDOs still face challenges with overuse of antibiotics for acute
      respiratory infections (ARI) and simple diarrhea, which contributes to the
      emergence of drug resistance. This study aimed to explore the attitudes of ADDO
      owners and dispensers toward antibiotic dispensing and to learn how accreditation
      has influenced their dispensing behavior. METHODS: The study used a qualitative
      approach. We conducted in-depth interviews with ADDO owners and dispensers in
      Ruvuma and Tanga regions where the government implemented the ADDO program under
      centralized and decentralized approaches, respectively; a secondary aim was to
      compare differences between the two regions. RESULTS: Findings indicate that the
      ADDO program has brought about positive changes in knowledge of dispensing
      practices. Respondents were able to correctly explain treatment guidelines for
      ARI and diarrhea. Almost all dispensers and owners indicated that unnecessary use
      of antibiotics contributed to antimicrobial resistance. Despite this knowledge,
      translating it to appropriate dispensing practice is still low. Dispensers'
      behavior is driven by customer demand, habit ("mazoea"), following inappropriate
      health facility prescriptions, and the need to make a profit. Although the
      majority of dispensers reported that they had intervened in situations where
      customers asked for antibiotics unnecessarily, they tended to give in to clients'
      requests. Small variations were noted between the two study regions; for example,
      some dispensers in Ruvuma reported sending clients with incorrect prescriptions
      back to the health facility, a practice that may reflect regional differences in
      ADDO implementation and in Integrated Management of Childhood Illness training.
      Dispensers in rural settings reported more challenges in managing ARI and
      diarrhea than their urban counterparts did. CONCLUSION: To reduce inappropriate
      antibiotic use, integrated interventions must include communities, health
      facilities, and ADDOs. Periodic refresher training with an emphasis on
      communication skills is crucial in helping dispensers deal with customers who
      demand antibiotics. Responsible authorities should ensure that ADDOs always have
      the necessary tools and resources available.

PMID- 26199724
TI  - Mother-to-Child Transmission of Hepatitis C Virus (HCV) Among HIV/HCV-Coinfected
      Women.
AB  - BACKGROUND: Maternal human immunodeficiency virus (HIV) coinfection has been
      associated with increased hepatitis C virus (HCV) mother-to-child transmission
      (MTCT). We hypothesized that HCV/HIV-coinfected women with well-controlled HIV
      disease would not have increased HCV MTCT. METHODS: The NISDI Perinatal and LILAC
      cohorts enrolled HIV-infected pregnant women and their infants in Latin America
      and the Caribbean. This substudy evaluated the HCV infection status of mothers at
      participating sites and their live born, singleton infants who had a 6-month
      postnatal visit by December 31, 2008. Mothers who were anti-HCV-positive, or who
      had CD4 counts (cells/mm(3)) <200 with detectable HCV RNA, were considered HCV
      infected. All HCV-infected women were tested for HCV RNA. Infants with HCV RNA
      were considered HCV-infected. RESULTS: Of 1042 enrolled women, 739 (71%) mother
      infant pairs met the inclusion criteria. Of the 739 women, 67 (9%) were anti-HCV
      positive and 672 anti-HCV-negative [68 (10%) with CD4 counts <200; of these, 3
      (4.4%) were HCV RNA-positive]. Therefore, our study population comprised 70 HCV
      infected (47 with HCV RNA) and 669 HCV-uninfected women (and their infants).
      Factors associated with maternal HCV infection included unemployment (odds ratio
      [OR] = 2.58); tobacco (OR = 1.73) or marijuana (OR = 3.88) use during pregnancy;
      enrollment HIV viral load ([VL] copies/mL) >=10 000 (OR = 2.27); HIV clinical
      disease stage C (OR = 2.12); and abnormal alanine aminotransferase (OR = 4.24) or
      aspartate aminotransferase (OR = 11.98). Four of 47 infants (8.5%) born to HCV
      viremic women were HCV-infected, and all 4 mothers had HIV VL <1000 at hospital
      discharge after delivery. CONCLUSIONS: HCV MTCT among HIV/HCV-coinfected women
      with well-controlled HIV disease may be lower than reported in other coinfected
      populations. Studies with longer infant follow-up are needed.

PMID- 26199726
TI  - Study of correlation between forced vital capacity and demand for healthcare
      services in severe asthmatics.
AB  - BACKGROUND: Involvement of the small airways may be related to increased severity
      and increased demand for health care services and incurring in high costs,
      private or for the healthcare system. The hyperinflation consequent to this
      involvement reduces lung volumes, such as FVC, FEV1 and SVC. The aim of this
      study was to evaluate the correlation between the predicted values of FVC, FEV1
      and SVC with the demand for healthcare services by severe asthmatics. METHODS: We
      retrospectively evaluated in order of arrival, the medical records of 98 patients
      with severe asthma, in step 4 treatment in the intercritical period of the
      disease, correlating the number of times each patient sought health care services
      represented by admissions to the ER, ICU and hospital wards due to asthma, in the
      year before the last spirometry and the predicted values of FVC, FEV1 and SVC.
      RESULTS: Our sample showed a clear and significant negative correlation between
      the predicted values of FVC, FEV1 and SVC and demand for healthcare services.
      CONCLUSION: For this sample we conclude, that reduced forced vital capacity
      correlated with asthma severity, defined by greater demand for care in the ER,
      ICU and hospital ward and was more evident in women.

PMID- 26199725
TI  - The scope for manipulating the polyunsaturated fatty acid content of beef: a
      review.
AB  - Since 1950, links between intake of saturated fatty acids and heart disease have
      led to recommendations to limit consumption of saturated fatty acid-rich foods,
      including beef. Over this time, changes in food consumption patterns in several
      countries including Canada and the USA have not led to improvements in health.
      Instead, the incidence of obesity, type II diabetes and associated diseases have
      reached epidemic proportions owing in part to replacement of dietary fat with
      refined carbohydrates. Despite the content of saturated fatty acids in beef, it
      is also rich in heart healthy cis-monounsaturated fatty acids, and can be an
      important source of long-chain omega-3 (n-3) fatty acids in populations where
      little or no oily fish is consumed. Beef also contains polyunsaturated fatty acid
      biohydrogenation products, including vaccenic and rumenic acids, which have been
      shown to have anticarcinogenic and hypolipidemic properties in cell culture and
      animal models. Beef can be enriched with these beneficial fatty acids through
      manipulation of beef cattle diets, which is now more important than ever because
      of increasing public understanding of the relationships between diet and health.
      The present review examines recommendations for beef in human diets, the need to
      recognize the complex nature of beef fat, how cattle diets and management can
      alter the fatty acid composition of beef, and to what extent content claims are
      currently possible for beef fatty acids. 

PMID- 26199727
TI  - Immune monitoring technology primer: the enzyme-linked immunospot (Elispot) and
      Fluorospot assay.

PMID- 26199729
TI  - Update on checkpoint blockade therapy for lymphoma.
AB  - Although cancer cells express antigens recognizable to the immune system, tumors
      employ a number of diverse mechanisms aimed at subverting the host anti-tumor
      immune response. Tumor immune evasion pathways have been most thoroughly studied
      in solid tumors. However, emerging data has demonstrated that malignancies of
      hematopoietic origin are also able to co-opt their local environment in order to
      escape immune attack. Activated T cells upregulate negative costimulatory
      receptors, such as programmed death-1 (PD-1) and cytotoxic lymphocyte antigen-4
      (CTLA-4). Engagement of PD-1 or CTLA-4 with ligands expressed on tumor cells or
      professional antigen presenting cells results in down-regulation of effector T
      cell function and represents a potent mechanism of immune evasion across a number
      of human cancers. Antibodies which block PD-1 / PD-L1 interactions have
      demonstrated remarkable activity in a number of solid tumor subtypes.
      Interestingly, recent data have demonstrated that in select subtypes of Hodgkin
      (HL) and non-Hodgkin lymphoma (NHL), the PD-1 ligands are over-expressed due to a
      genetic amplification of the loci encoding them. Other mechanisms of PD-L1 over
      expression in lymphoma have also been elucidated. Reports from early-phase
      clinical trials of PD-1 blockade have demonstrated remarkable effectiveness in
      HL, and also appear active against some NHLs. We review the mechanisms of PD-L1
      expression in lymphoma and also the early results of anti-PD-1 therapy in this
      disease. 

PMID- 26199728
TI  - Route of antigen delivery impacts the immunostimulatory activity of dendritic
      cell-based vaccines for hepatocellular carcinoma.
AB  - BACKGROUND: Dendritic cells (DC) are uniquely equipped to capture, process, and
      present antigens from their environment. The context in which an antigen is
      acquired by DC helps to dictate the subsequent immune response. Cancer
      vaccination promotes antitumor immunity by directing an immune response to
      antigens expressed by tumors. We have tested the tumor-associated antigen alpha
      fetoprotein (AFP) as an immunotherapy target. The majority of hepatocellular
      carcinomas (HCC) upregulate and secrete this oncofetal antigen. METHODS: To
      develop cancer vaccines for HCC capable of promoting potent tumor-specific T cell
      responses, we tested adenovirally-encoded synthetic AFP, with or without its
      signal sequence, as well as protein forms of AFP and compared intracellular
      routing and subsequent antigen-specific CD8+ and CD4+ T cell responses. RESULTS:
      Surprisingly, the secreted form of antigen was superior for both CD4+ and CD8+ T
      cell activation. We also examined the mechanism through which AFP protein is
      endocytosed and trafficked in human DC. We identify the mannose receptor
      (MR/CD206) as the primary uptake pathway for both normal cord blood-derived AFP
      (nAFP) and tumor-derived AFP (tAFP) proteins. While in healthy donors, nAFP and
      tAFP were cross-presented to CD8+ T cells similarly and CD4+ T cell responses
      were dependent upon MR-mediated uptake. In HCC patient cells, tAFP was more
      immunogenic, and CD4+ T cell responses were not MR-dependent. CONCLUSIONS:
      Secreted, cytoplasmically retained, and endocytosed forms of AFP utilize unique
      uptake and processing pathways, resulting in different immunologic responses from
      the induced antigen-specific CD4+ and CD8+ T cells and between healthy donors and
      HCC patients. Collectively, these data elucidate pathways of spontaneous and
      induced anti-tumor immunity in HCC patients to this secreted antigen.

PMID- 26199730
TI  - Use of a fixed, body weight-unadjusted loading dose of unfractionated heparin for
      extracorporeal cardiopulmonary resuscitation.
AB  - BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is being used
      increasingly in the emergency and critical care field in Japan. A major
      complication of ECPR is bleeding; however, the optimal initial heparin dose and
      activated coagulation time (ACT) remain unknown. The aim of this study was to
      assess the appropriateness of our initial anticoagulation protocol. METHODS: We
      retrospectively evaluated the initial heparin dose, ACT value, and incidence of
      bleeding and thrombotic complications in post-cardiopulmonary arrest patients who
      received a fixed, body weight-unadjusted loading dose of unfractionated heparin
      (3000 U) prior to veno-arterial extracorporeal membrane oxygenator (ECMO) between
      February 2011 and November 2013 at Mie University Hospital, Japan. RESULTS: ACT
      was evaluated within 3 h of initiation of 32 consecutive ECPR patients. The mean
      heparin dose per body weight was 53.6 U/kg and the mean ACT was 231.3 s. In 17
      patients, ACT exceeded 200 s. Three patients experienced fatal bleeding in the
      chest wall within 24 h of receiving ECMO. The mean heparin dose per kilogram body
      weight, mean initial ACT, and mean duration of cardiopulmonary resuscitation
      (CPR) did not statistically differ between the patients who experienced fatal
      bleeding and those who did not. CONCLUSIONS: Fixed-dose heparin of 3000-U bolus
      resulted in a mean heparin dose per kilogram body weight of 53.6 U/kg and an ACT
      of 231.3 s and experienced 3 out of 32 fatal bleedings. Further researches are
      warranted to optimize anticoagulation protocol for ECPR patients.

PMID- 26199731
TI  - Serologic and molecular survey for hepatitis E virus in wild boar (Sus scrofa) in
      Central Italy.
AB  - The aim of this study was to further investigate the role of wild boar (Sus
      scrofa) as a reservoir for hepatitis E virus (HEV). Sixty-four blood and faecal
      samples collected from wild boar hunted in Central Italy in 2011-2012 were
      examined by indirect enzyme-linked immunosorbent assay and RT-PCR analysis.
      Positive RT-PCR samples were further examined by nucleotide sequence
      determination and subsequent phylogenetic analysis. Thirty-six sera (56.2%) were
      positive for HEV-specific antibodies, and six (9.4%) faecal samples scored RT-PCR
      positive results. Four animals were positive by both enzyme-linked immunosorbent
      assay and RT-PCR. Phylogenetic analysis showed that the detected wild boar
      derived HEV sequences clustered within genotype 3, with similarity to sequences
      of human origin collected in a nearby area in 2012. Our data confirm that HEV is
      endemic in the wild boar population in the research area and that these wild
      animals could play an important role in the epidemiology of HEV infection. 

PMID- 26199732
TI  - New Microbes New Infections promotes modern prokaryotic taxonomy: a new section
      "TaxonoGenomics: new genomes of microorganisms in humans".

PMID- 26199733
TI  - Enterococcus cecorum human infection, France.
AB  - Enterococcus cecorum is a bacterium of the intestinal tract of many domestic
      animals that is rarely reported as human pathogen. Here we report the first case
      of incisional hernia plate infection and the first case of urinary tract
      colonization due to E. cecorum from patients in Marseille, France. 

PMID- 26199734
TI  - Parents' preferences and willingness-to-pay for human papilloma virus vaccines in
      Thailand.
AB  - OBJECTIVE: To examine parents' preferences and willingness-to-pay (WTP) for HPV
      vaccines. METHODS: A discrete choice experiment (DCE) was used. Parents with at
      least one daughter aged 9-13 years residing in Songkhla province were asked to
      choose one alternative from each DCE choice set describing HPV vaccines by four
      attributes, including cervical cancer risk reduction, genital warts risk
      reduction, common side effects, and cost. Multinomial logit model was used for
      data analyses. RESULTS: Parents preferred higher risk reductions for cervical
      cancer and genital warts, and lower common side effects. They valued the
      quadrivalent and bivalent HPV vaccines at 21,189.9 and 10,479.9 Baht,
      respectively. Results also showed that mothers valued both vaccines more than
      fathers did. CONCLUSIONS: Parents valued net benefits for both quadrivalent and
      bivalent HPV vaccines, but they were willing to pay for the quadrivalent vaccine
      more than for the bivalent vaccine.

PMID- 26199736
TI  - Proximal Tubular Injury in Medullary Rays Is an Early Sign of Acute Tacrolimus
      Nephrotoxicity.
AB  - Tacrolimus (FK506) is one of the principal immunosuppressive agents used after
      solid organ transplantations to prevent allograft rejection. Chronic renal injury
      induced by tacrolimus is characterized by linear fibrosis in the medullary rays;
      however, the early morphologic findings of acute tacrolimus nephrotoxicity are
      not well characterized. Kidney injury molecule-1 (KIM-1) is a specific injury
      biomarker that has been proven to be useful in the diagnosis of mild to severe
      acute tubular injury on renal biopsies. This study was motivated by a patient
      with acute kidney injury associated with elevated serum tacrolimus levels in whom
      KIM-1 staining was present only in proximal tubules located in the medullary rays
      in the setting of otherwise normal light, immunofluorescent, and electron
      microscopy. We subsequently evaluated KIM-1 expression in 45 protocol and 39
      indicated renal transplant biopsies to determine whether higher serum levels of
      tacrolimus were associated with acute segment specific injury to the proximal
      tubule, as reflected by KIM-1 staining in the proximal tubules of the cortical
      medullary rays. The data suggest that tacrolimus toxicity preferentially affects
      proximal tubules in medullary rays and that this targeted injury is a precursor
      lesion for the linear fibrosis seen in chronic tacrolimus toxicity. 

PMID- 26199735
TI  - Screening agars for MRSA: evaluation of a stepwise diagnostic approach with two
      different selective agars for the screening for methicillin-resistant
      Staphylococcus aureus (MRSA).
AB  - BACKGROUND: Colonization with methicillin-resistant Staphylococcus aureus (MRSA)
      poses a hygiene risk that does not spare field hospitals or military medical
      field camps during military deployments. Diagnostic options for unambiguously
      identifying MRSA isolates are usually scarce in military environments. In this
      study, we assessed the stepwise application of two different selective agars for
      the specific identification of MRSA in screening analyses. METHODS: Nasal swabs
      from 1541 volunteers were subjected to thioglycollate broth enrichment and
      subsequently screened on CHROMagar MRSA selective agar for the identification of
      MRSA. The MRSA identity of suspicious-looking colonies was confirmed afterwards
      or excluded by another selective agar, chromID MRSA. All isolates from the
      selective agars with MRSA-specific colony morphology were identified by
      biochemical methods and mass spectrometry. RESULTS: The initial CHROMagar MRSA
      screening identified suspicious colonies in 36 out of 1541 samples. A total of 25
      of these 36 isolates showed MRSA-like growth on chromID agar. Out of these 25
      isolates, 24 were confirmed as MRSA, while one isolate was identified as
      Staphylococcus kloosii. From the 11 strains that did not show suspicious growth
      on chromID agar, 3 were methicillin-sensitive Staphylococcus aureus (MSSA, with
      one instance of co-colonization with Corynebacterium spp.), 2 were confirmed as
      MRSA (with 1 instance of co-colonization with MSSA), 2 were lost during passaging
      and could not be re-cultured, one could not be identified by the applied
      approaches, and the remaining 3 strains were identified as Staphylococcus
      saprophyticus, Staphylococcus hominis (co-colonized with Macrococcus
      caseolyticus) and Staphylococcus cohnii, respectively. CONCLUSIONS: The
      application of the selective agar CHROMagar MRSA alone proved to be too non
      specific to allow for a reliable diagnosis of the presence of MRSA. The combined
      use of two selective agars in a stepwise approach reduced this non-specificity
      with an acceptably low loss of sensitivity. Accordingly, such a stepwise
      screening approach might be an option for resource-restricted military medical
      field camps.

PMID- 26199737
TI  - Comparison of Fourier-Domain and Time-Domain Optical Coherence Tomography in the
      Measurement of Thinnest Corneal Thickness in Keratoconus.
AB  - Objective. To compare fourier-domain optical coherence tomography (FD-OCT) and
      time-domain OCT (TD-OCT) in the determination of thinnest corneal thickness
      (TCT). Methods. This study included 55 keratoconus patients and 50 healthy
      volunteers. The RTVue-OCT (FD-OCT) and Visante-OCT (TD-OCT) were used for the
      measurement of the TCT. Three consecutive scans were performed. The comparison
      and agreement between the two modalities were analyzed by paired t-test, the
      Pearson correlation, intraclass correlation coefficient (ICC), and Bland-Altman
      plots. intraobserver repeatability was analyzed by the intraobserver within
      subject standard deviation (S (w)), coefficient of variation (CV(w)), and ICC.
      Results. The TCT value of normal corneas was higher by RTVue-OCT (530.4 +/- 19.7
      MUm) than Visante-OCT (521.5 +/- 18.3 MUm) (p < 0.001). For keratoconus eyes, the
      TCT was 425.0 +/- 58.2 MUm and 424.4 +/- 55.7 MUm (difference being 0.6 +/- 10.2
      MUm, p = 0.604). Strong correlation (r = 0.938~0.985) (ICC = 0.915-0.984) was
      observed between the two OCTs, and each OCT exhibited excellent repeatability in
      determining the TCT in all subjects (ICC = 0.984-0.994). Conclusions. The values
      of TCT obtained from RTVue-OCT and Visante-OCT were highly correlated; however,
      the two values were different. Both OCT instruments exhibited good intraobserver
      reliability. The existence of systematic differences suggested that the two
      instruments cannot be used interchangeably. 

PMID- 26199738
TI  - Deep Sclerectomy with Goniosynechiolysis Ab Interno for Chronic Glaucoma
      Associated with Peripheral Anterior Synechiae.
AB  - Purpose. To report one-year results of phacoemulsification combined with deep
      sclerectomy and goniosynechiolysis ab interno for chronic glaucoma associated
      with peripheral anterior synechiae (PAS). Methods. We retrospectively analyzed
      medical charts of 16 patients (20 eyes) treated by one-site combined
      phacoemulsification and deep sclerectomy with goniosynechiolysis ab interno. PAS
      were transected by a spatula introduced into the anterior chamber through a
      paracentesis. To account for the correlation of right and left eyes a linear
      mixed model with unstructured covariance structure was calculated. Results. The
      mean preoperative intraocular pressure (IOP) was 20.3 +/- 5.2 mmHg with 2.4 +/-
      1.0 medications. One year postoperatively, the mean IOP was 15.3 +/- 3.3 mmHg (P
      = 0.004, paired t-test) with 0.6 +/- 1.0 medications. A postoperative IOP of <=21
      mmHg without medication was achieved in 17 of 19 eyes (89.5%) and in 12/19 eyes
      (63.2%) at 3 and 12 months after surgery, respectively. In the remaining eyes
      (10.5% at 3 months and 36.8% at 12 months), additional medication led to an IOP
      <=21 mmHg or the target pressure. No case required further glaucoma surgery. In
      one eye, conversion of the surgery to trabeculectomy was necessary due to
      Descemet's window rupture. Conclusions. With goniosynechiolysis ab interno,
      effective and safe nonpenetrating glaucoma surgery is possible in presence of
      PAS. 

PMID- 26199739
TI  - Factors Influencing Efficacy of Peripheral Corneal Relaxing Incisions during
      Cataract Surgery.
AB  - Purpose. To evaluate influencing factors on the residual astigmatism after
      performing peripheral corneal relaxing incisions (PCRIs) during cataract surgery.
      Methods. This prospective study included patients who were scheduled for cataract
      surgery with PCRIs. Optical biometry (IOLMaster 500, Carl Zeiss Meditec AG,
      Germany) was taken preoperatively, 1 week, 4 months, and 1 year postoperatively.
      Additionally, corneal topography (Atlas model 9000, Carl Zeiss Meditec AG,
      Germany), ORA (Ocular Response Analyzer, Reichert Ophthalmic Instruments, USA),
      and autorefraction (Autorefractometer RM 8800 Topcon) were performed
      postoperatively. Results. Mean age of the study population (n = 74) was 73.5
      years (+/-9.3; range: 53 to 90) and mean corneal astigmatism preoperatively was 
      1.82 D (+/-0.59; 1.00 to 4.50). Mean corneal astigmatism was reduced to 1.14 D
      (+/-0.67; 0.11 to 3.89) 4 months postoperatively. A partial least squares
      regression showed that a high eccentricity of the cornea, a large deviation
      between keratometry and topography, and a high preoperative astigmatism resulted
      in a larger postoperative error concerning astigmatism. Conclusions. PCRI causes
      a reduction of preoperative astigmatism, though the prediction is difficult but
      several factors were found to be a relevant source of error. 

PMID- 26199740
TI  - Feasibility and Impact of a Combined Supervised Exercise and Nutritional
      Behavioral Intervention following Bariatric Surgery: A Pilot Study.
AB  - BACKGROUND: Lifestyle intervention programs after bariatric surgery have been
      suggested to maximise health outcomes. This pilot study aimed to investigate the
      feasibility and impact of an 8-week combined supervised exercise with nutritional
      behavioral intervention following Roux-en-Y gastric bypass and sleeve
      gastrectomy. METHODS: Eight female patients (44 +/- 8 years old, BMI = 38.5 +/-
      7.2 kg m(-2)) completed the program. Before and after intervention,
      anthropometric measures, six-minute walk test (6MWT), physical activity level,
      eating behavior, and quality of life (QoL) were assessed. Percentage weight loss
      (%WL) outcomes were compared with a historical matched control group. RESULTS:
      The program significantly improved functional capacity (mean increment in 6MWT
      was 127 +/- 107 meters, p = 0.043), increased strenuous intensity exercise (44 +/
      49 min/week, p = 0.043), increased consumption of fruits and vegetables (p =
      0.034), reduced consumption of ready meals (p = 0.034), and improved "Change in
      Health" in QoL domain (p = 0.039). The intervention group exhibited greater %WL
      in the 3-12-month postsurgery period compared to historical controls, 12.2 +/-
      7.5% versus 5.1 +/- 5.4%, respectively (p = 0.027). CONCLUSIONS: Lifestyle
      intervention program following bariatric surgery is feasible and resulted in
      several beneficial outcomes. A large randomised control trial is now warranted.

PMID- 26199741
TI  - Targeting Feeding and Eating Behaviors: Development of the Feeding Dynamic
      Intervention for Caregivers of 2- to 5-Year-Old Children.
AB  - Targeting feeding dynamics, a concept centered on the roles and interaction of
      the caregiver and child in a feeding relationship, may have significant potential
      for obesity intervention. The aim of this paper is to describe the 3-phase
      development of the Feeding Dynamics Intervention (FDI), an acceptability and
      feasibility study on implementing the feeding dynamic roles (Study 1),
      development of the FDI content (Study 2), and a pilot study on use of the 6
      lesson FDI to promote behaviors consistent with a feeding dynamic approach (Study
      3). Sample population was mothers with young children, 2-5 years old. An effect
      size (Hedges' g) greater than 0.20 was seen in more than half (57%) of maternal
      feeding behaviors, with the largest effect sizes (Hedges' g >= 0.8) occurring
      with behaviors that represent the mother adopting her roles of determining what
      food is served, not using food as a reward, and not controlling her child's
      intake. There was a significant decline in Pressure to Eat behaviors (2.9 versus
      2.2, p < 0.01) and Monitoring (4.1 versus 3.5, p < 0.001). The FDI emerged as an
      acceptable and implementable intervention. Future studies need to investigate
      effects of the FDI on the child's eating behaviors, self-regulation of energy
      intake, and anthropometrics. 

PMID- 26199743
TI  - Contaminated water as a source of Helicobacter pylori infection: A review.
AB  - Over the preceding years and to date, the definitive mode of human infection by
      Helicobacter pylori has remained largely unknown and has thus gained the interest
      of researchers around the world. Numerous studies investigated possible sources
      of transmission of this emerging carcinogenic pathogen that colonizes >50% of
      humans, in many of which contaminated water is mentioned as a major cause. The
      infection rate is especially higher in developing countries, where contaminated
      water, combined with social hardships and poor sanitary conditions, plays a key
      role. Judging from the growing global population and the changing climate, the
      rate is expected to rise. Here, we sum up the current views of the water
      transmission hypothesis, and we discuss its implications. 

PMID- 26199745
TI  - Electrical and optical properties of nickel ferrite/polyaniline nanocomposite.
AB  - Polyaniline-NiFe2O4 nanocomposites (PANI-NiFe2O4) with different contents of
      NiFe2O4 (2.5, 5 and 50 wt%) were prepared via in situ chemical oxidation
      polymerization, while the nanoparticles nickel ferrite were synthesized by sol
      gel method. The prepared samples were characterized using some techniques such as
      Fourier transforms infrared (FTIR), X-ray diffraction (XRD), scanning electron
      microscopy (SEM) and thermogravimetric analysis (TGA). Moreover, the electrical
      conductivity and optical properties of the nanocomposites were investigated. Pure
      (PANI) and the composites containing 2.5 and 5 wt% NiFe2O4 showed amorphous
      structures, while the one with 50 wt% NiFe2O4 showed a spinel crystalline
      structure. The SEM images of the composites showed different aggregations for the
      different nickel ferrite contents. FTIR spectra revealed to the formation of some
      interactions between the PANI macromolecule and the NiFe2O4 nanoparticles, while
      the thermal analyses indicated an increase in the composites stability for
      samples with higher NiFe2O4 nanoparticles contents. The electrical conductivity
      of PANI-NiFe2O4 nanocomposite was found to increase with the rise in NiFe2O4
      nanoparticle content, probably due to the polaron/bipolaron formation. The
      optical absorption experiments illustrate direct transition with an energy band
      gap of Eg  = 1.0 for PANI-NiFe2O4 nanocomposite. 

PMID- 26199742
TI  - Fructose Metabolism and Relation to Atherosclerosis, Type 2 Diabetes, and
      Obesity.
AB  - A high intake of sugars has been linked to diet-induced health problems. The
      fructose content in sugars consumed may also affect health, although the extent
      to which fructose has a particularly significant negative impact on health
      remains controversial. The aim of this narrative review is to describe the body's
      fructose management and to discuss the role of fructose as a risk factor for
      atherosclerosis, type 2 diabetes, and obesity. Despite some positive effects of
      fructose, such as high relative sweetness, high thermogenic effect, and low
      glycaemic index, a high intake of fructose, particularly when combined with
      glucose, can, to a larger extent than a similar glucose intake, lead to metabolic
      changes in the liver. Increased de novo lipogenesis (DNL), and thus altered blood
      lipid profile, seems to be the most prominent change. More studies with realistic
      consumption levels of fructose are needed, but current literature does not
      indicate that a normal consumption of fructose (approximately 50-60 g/day)
      increases the risk of atherosclerosis, type 2 diabetes, or obesity more than
      consumption of other sugars. However, a high intake of fructose, particularly if
      combined with a high energy intake in the form of glucose/starch, may have
      negative health effects via DNL. 

PMID- 26199744
TI  - Plague in Egypt: Disease biology, history and contemporary analysis: A
      minireview.
AB  - Plague is a zoonotic disease with a high mortality rate in humans. Unfortunately,
      it is still endemic in some parts of the world. Also, natural foci of the disease
      are still found in some countries. Thus, there may be a risk of global plague re
      emergence. This work reviews plague biology, history of major outbreaks, and
      threats of disease re-emergence in Egypt. Based on the suspected presence of
      potential natural foci in the country, the global climate change, and the threat
      posed by some neighbouring countries disease re-emergence in Egypt should not be
      excluded. The country is in need for implementation of some preventive measures. 

PMID- 26199746
TI  - The role of MgBr2 to enhance the ionic conductivity of PVA/PEDOT:PSS polymer
      composite.
AB  - A solid polymer electrolyte system based on poly(vinyl alcohol) (PVA) and
      poly(3,4-Etylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) complexed
      with magnesium bromide (MgBr2) salt was prepared using solution cast technique.
      The ionic conductivity is observed to increase with increasing MgBr2
      concentration. The maximum conductivity was found to be 9.89 * 10(-6) S/cm for
      optimum polymer composite film (30 wt.% MgBr2) at room temperature. The increase
      in the conductivity is attributed to the increase in the number of ions as the
      salt concentration is increased. This has been proven by dielectric studies. The
      increase in conductivity is also attributable to the increase in the fraction of
      amorphous region in the electrolyte films as confirmed by their structural,
      thermal, electrical and optical properties.

PMID- 26199747
TI  - Efficient and reversible CO2 capture by amine functionalized-silica gel confined
      task-specific ionic liquid system.
AB  - Simple, efficient and practical CO2 capture method is reported using task
      specific ionic liquid (IL) supported onto the amine-functionalized silica gel.
      The results have been shown that both the capacity and rate of the CO2 absorption
      notably increase in the supported IL/molecular sieve 4 A system in comparison of
      homogeneous IL. Additionally, it has shown that the prepared material is capable
      for reversible carbon dioxide absorption for at least 10 cycles without
      significant loss of efficiency. The presence of the amine-based IL and the
      surface bonded amine groups increase the capacity of CO2 absorption even in a
      CO2/CH4 gas mixture through the formation of ammonium carbamate onto the surface
      of mesoporous material. 

PMID- 26199748
TI  - Impact of landfill leachate on the groundwater quality: A case study in Egypt.
AB  - Alexandria Governorate contracted an international company in the field of
      municipal solid waste management for the collection, transport and disposal of
      municipal solid waste. Construction and operation of the sanitary landfill sites
      were also included in the contract for the safe final disposal of solid waste. To
      evaluate the environmental impacts associated with solid waste landfilling,
      leachate and groundwater quality near the landfills were analyzed. The results of
      physico-chemical analyses of leachate confirmed that its characteristics were
      highly variable with severe contamination of organics, salts and heavy metals.
      The BOD5/COD ratio (0.69) indicated that the leachate was biodegradable and un
      stabilized. It was also found that groundwater in the vicinity of the landfills
      did not have severe contamination, although certain parameters exceeded the WHO
      and EPA limits. These parameters included conductivity, total dissolved solids,
      chlorides, sulfates, Mn and Fe. The results suggested the need for adjusting
      factors enhancing anaerobic biodegradation that lead to leachate stabilization in
      addition to continuous monitoring of the groundwater and leachate treatment
      processes. 

PMID- 26199749
TI  - A unified classification model for modeling of seismic liquefaction potential of
      soil based on CPT.
AB  - The evaluation of liquefaction potential of soil due to an earthquake is an
      important step in geosciences. This article examines the capability of Minimax
      Probability Machine (MPM) for the prediction of seismic liquefaction potential of
      soil based on the Cone Penetration Test (CPT) data. The dataset has been taken
      from Chi-Chi earthquake. MPM is developed based on the use of hyperplanes. It has
      been adopted as a classification tool. This article uses two models (MODEL I and
      MODEL II). MODEL I employs Cone Resistance (q c) and Cyclic Stress Ratio (CSR) as
      input variables. q c and Peak Ground Acceleration (PGA) have been taken as inputs
      for MODEL II. The developed MPM gives 100% accuracy. The results show that the
      developed MPM can predict liquefaction potential of soil based on q c and PGA. 

PMID- 26199750
TI  - On shallow water waves in a medium with time-dependent dispersion and
      nonlinearity coefficients.
AB  - In this paper, we studied the progression of shallow water waves relevant to the
      variable coefficient Korteweg-de Vries (vcKdV) equation. We investigated two
      kinds of cases: when the dispersion and nonlinearity coefficients are
      proportional, and when they are not linearly dependent. In the first case, it was
      shown that the progressive waves have some geometric structures as in the case of
      KdV equation with constant coefficients but the waves travel with time dependent
      speed. In the second case, the wave structure is maintained when the nonlinearity
      balances the dispersion. Otherwise, water waves collapse. The objectives of the
      study are to find a wide class of exact solutions by using the extended unified
      method and to present a new algorithm for treating the coupled nonlinear PDE's. 

PMID- 26199751
TI  - Potential risk factors associated with ill-thrift in buffalo calves (Bubalus
      bubalis) raised at smallholder farms in Egypt.
AB  - Failure to grow (ill-thrift) in calves has a negative effect on animal production
      and health. The present study was carried out from November, 2009 to May, 2013 to
      investigate the risk factors of ill-thrift in buffalo calves. A total of 344
      calves at 78 smallholder farms were selected randomly. A questionnaire was
      designed to include managemental, nutritional and disease risk factors. Serum
      selenium, copper, zinc, iron, calcium, phosphorus and magnesium were measured.
      Data were subjected to logistic regression analysis and results were expressed as
      p value, odds ratio (OR) and confidence interval (CI). Fifty-five calves (15.9%)
      showed ill-thrift. On animal level, the final multivariate logistic regression
      model showed a significant association between ill-thrift and early weaning (p <
      0.01; OR: 45.755; CI: 4.35-480.25), diarrhea (p < 0.05; OR: 41.315; CI: 1.710
      998.0), indoor management (p < 0.05; OR: 63.56; CI: 2.701-14.96) and low serum
      phosphorus (p < 0.01; 292.0; CI: 5.256-16.23). On farm level, inadequate mineral
      supplementation (p < 0.001; OR: 18.62; CI: 3.89-88.9) and irregular use of
      anthelmintics (p < 0.05; OR: 7.95; CI: 1.53-41.23) were the potential factors.
      Clinically, ill-thrift calves were more likely to have alopecia (p < 0.01),
      recumbency (p < 0.01), emaciation (p < 0.001), hypothermia (p < 0.01),
      inappetance (p < 0.001), lacrimation (p < 0.001), hypomotile rumen (p < 0.001),
      and pale mucous membrane (p < 0.001). The results of the present study indicate
      that ill-thrift in buffalo calves could occur as a result of interaction between
      management errors and disease factors. Identification of the risk factors
      associated with ill-thrift may provide useful information, which assist to
      construct the suitable preventive measures. 

PMID- 26199752
TI  - A hybrid approach for efficient anomaly detection using metaheuristic methods.
AB  - Network intrusion detection based on anomaly detection techniques has a
      significant role in protecting networks and systems against harmful activities.
      Different metaheuristic techniques have been used for anomaly detector
      generation. Yet, reported literature has not studied the use of the multi-start
      metaheuristic method for detector generation. This paper proposes a hybrid
      approach for anomaly detection in large scale datasets using detectors generated
      based on multi-start metaheuristic method and genetic algorithms. The proposed
      approach has taken some inspiration of negative selection-based detector
      generation. The evaluation of this approach is performed using NSL-KDD dataset
      which is a modified version of the widely used KDD CUP 99 dataset. The results
      show its effectiveness in generating a suitable number of detectors with an
      accuracy of 96.1% compared to other competitors of machine learning algorithms. 

PMID- 26199753
TI  - Eubiotic effect of a dietary acidifier (potassium diformate) on the health status
      of cultured Oreochromis niloticus.
AB  - In connection with the global demand for safe human food and the production of
      environmentally friendly aquaculture products, acidifiers are natural organic
      acids and salts that have received considerable attention as animal-feed
      additives. The current study was designed to evaluate the effects of potassium
      diformate (KDF) on the growth performance and immunity of cultured Oreochromis
      niloticus (O. niloticus). Four iso-nitrogenous and iso-caloric rations containing
      graded levels of KDF, including 0% (control basal diet), 0.1%, 0.2% and 0.3%,
      were fed separately to four equal fish groups (30 fish/group with an initial body
      weight of 53.49 +/- 6.15 g) for sixty days. At the end of the experimental
      period, the fish groups fed on 0.2% and 0.3% KDF exhibited significant
      improvements in their feed intake, live weight gain, specific growth rate, feed
      conversion ratio and protein efficiency ratio, with concomitant improvement of
      their apparent protein digestibility (p < 0.05). Dietary supplementation of 0.3%
      KDF appeared to stimulate the beneficial intestinal flora; a proliferation was
      observed of indigenous probionts (Eubiosis) associated with the relative
      activation of cellular and humeral innate immunity (phagocytic activity/index,
      nitroblue tetrazolium reduction test and serum/gut mucous lysozyme activity). The
      cumulative mortality of the fish groups fed on KDF and challenged orally with
      Aeromonas hydrophila was lower than that of the control group. The resistance
      against diseases increased with dietary KDF in a dose-dependent manner. Thus, we
      conclude that the use of acidifiers can be an efficient tool to achieve
      sustainable, economical and safe fish production. 

PMID- 26199754
TI  - Benzoquinoline amines - Key intermediates for the synthesis of angular and linear
      dinaphthonaphthyridines.
AB  - A systematic study on the condensation reaction of 2,4-dichlorobenzo[h]quinoline
      and naphth-1-ylamine in the presence of CuI as catalyst to functionalised mono-
      and di-substituted (naphthalen-1-yl)benzo[h]quinoline amines was described.
      Subsequently these mono- and di-substituted amines on polyphosphoric acid
      catalysed cyclisation reaction with aromatic/heteroaromatic carboxylic acids led
      to the construction of angular and linear aromatic/heteroaromatic substituted
      dinaphthonaphthyridines in good yields. 

PMID- 26199755
TI  - Impact of a Simulation-Based Communication Workshop on Resident Preparedness for
      End-of-Life Communication in the Intensive Care Unit.
AB  - Introduction. Although residents frequently lead end-of-life (EOL) discussions in
      the intensive care unit (ICU), training in EOL care during residency has been
      required only recently, and few educational interventions target EOL
      communication in the ICU. This study evaluated a simulation-based intervention
      designed to improve resident EOL communication skills with families in the ICU.
      Methods. Thirty-four second-year internal medicine residents at a large urban
      teaching hospital participated in small group sessions with faculty trained in
      the "VitalTalk" method. A Likert-type scale questionnaire measured self-assessed
      preparedness before, immediately following, and approximately 9 months after
      intervention. Data were analyzed using Wilcoxon rank-sum analysis. Results. Self
      assessed preparedness significantly improved for all categories surveyed
      (preintervention mean; postintervention mean; p value), including discussing bad
      news (3.3; 4.2; p < 0.01), conducting a family conference (3.1; 4.1; p < 0.01),
      discussing treatment options (3.2; 3.9; p < 0.01), discussing discontinuing ICU
      treatments (2.9; 3.5; p < 0.01), and expressing empathy (3.9; 4.5; p < 0.01).
      Improvement persisted at follow-up for all items except "expressing empathy."
      Residents rated the educational quality highly. Conclusion. This study provides
      evidence that brief simulation-based interventions can produce lasting
      improvements in residents' confidence to discuss EOL care with family members of
      patients in the ICU. 

PMID- 26199756
TI  - Prevalence of Hepatitis E Virus among Adults in South-West of Iran.
AB  - Background. Knowledge regarding prevalence of HEV in general population can be an
      indicator of the public health and hygiene. Therefore, this study was conducted
      to evaluate the prevalence of HEV among adults in South-West of Iran. Methods.
      Blood samples were taken from 510 participants, 206 (40.4%) males and 304 (59.6%)
      females from February to July 2014. Detection of anti-HEV IgG and IgM antibodies
      was carried out by ELISA test. Results. The overall anti-HEV IgG and IgM
      prevalence rates were 46.1% and 1.4%, respectively. Anti-HEV IgG and IgM
      seropositivity were not statistically associated with gender and race/ethnicity.
      Meanwhile, there were significant differences between the age groups regarding
      HEV IgG and IgM seropositivity. HEV IgG seroprevalence increased with age from
      14.3% in subjects aged 18-30 years to 71.4% in persons over 71 years old, and
      considerably individuals aged 61 to 70 years had the highest HEV prevalence
      (90.9%). Also, 5.7% in the age group 18-30 years and 2.2% in the age group 31-40
      years were positive for anti-HEV IgM antibodies and the highest rate was observed
      in subjects aged 18-30 years. Conclusion. In conclusion, high HEV IgG
      seroprevalence of 46.1% was observed among adults in South-West of Iran. 

PMID- 26199757
TI  - Inventory of a Neurological Intensive Care Unit: Who Is Treated and How Long?
AB  - Purpose. To characterize indications, treatment, and length of stay in a stand
      alone neurological intensive care unit with focus on comparison between
      ventilated and nonventilated patient. Methods. We performed a single-center
      retrospective cohort study of all treated patients in our neurological intensive
      care unit between October 2006 and December 2008. Results. Overall, 512 patients
      were treated in the surveyed period, of which 493 could be included in the
      analysis. Of these, 40.8% had invasive mechanical ventilation and 59.2% had not.
      Indications in both groups were predominantly cerebrovascular diseases. Length of
      stay was 16.5 days in mean for ventilated and 3.6 days for nonventilated patient.
      Conclusion. Most patients, ventilated or not, suffer from vascular diseases with
      further impairment of other organ systems or systemic complications. Data
      reflects close relationship and overlap of treatment on nICU with a standardized
      stroke unit treatment and suggests, regarding increasing therapeutic options, the
      high impact of acute high-level treatment to reduce consequential complications. 

PMID- 26199758
TI  - Arousal Predisposition as a Vulnerability Indicator for Psychosis: A General
      Population Online Stress Induction Study.
AB  - Explanatory models ascribe to arousability a central role for the development of
      psychotic symptoms. Thus, a disposition to hyperarousal (i.e., increased arousal
      predisposition (AP)) may serve as an underlying vulnerability indicator for
      psychosis by interacting with stressors to cause symptoms. In this case, AP,
      stress-response, and psychotic symptoms should be linked before the development
      of a diagnosable psychotic disorder. We conducted a cross-sectional online study
      in a population sample (N = 104; M age = 27.7 years, SD = 11.2, range 18-70).
      Participants rated their AP and subclinical psychotic symptoms. Participants
      reported their stress-levels before and after two stress inductions including an
      arithmetic and a social stressor. The participants with an increased AP generally
      felt more stressed. However, AP was not associated with the specific stress
      response. As expected, positive psychotic symptoms were significantly associated
      with AP, but this was not mediated by general stress-levels. Its association to
      subtle, nonclinical psychotic symptoms supports our assumption that AP could be a
      vulnerability indicator for psychosis. The trait is easily accessible via a short
      self-report and could facilitate the identification of people at risk and be a
      promising target for early stress-management. Further research is needed to
      clarify its predictive value for stress-responses. 

PMID- 26199760
TI  - Pulmonic Valve Repair in a Patient with Isolated Pulmonic Valve Endocarditis and
      Sickle Cell Disease.
AB  - A 49-year-old woman with sickle cell disease presented with one month of
      exertional dyspnea, weakness, and fever and was diagnosed with isolated pulmonic
      valve endocarditis secondary to methicillin-resistant Staphylococcus bacteremia
      in the setting of a peripherally inserted central venous catheter. Chest
      computerized tomography showed multiple bilateral pulmonary nodular opacities
      consistent with septic emboli. Transthoracic and transesophageal echocardiograms
      revealed a large echodensity on the pulmonic valve requiring vegetation excision
      and pulmonic valve repair. In conclusion, isolated pulmonic valve endocarditis is
      a rare cause of infective endocarditis that warrants a high index of clinical
      suspicion. Furthermore the management of patients with sickle cell disease and
      endocarditis requires special consideration. 

PMID- 26199759
TI  - Characteristics of Adult T-Cell Leukemia/Lymphoma Patients with Long Survival:
      Prognostic Significance of Skin Lesions and Possible Beneficial Role of Valproic
      Acid.
AB  - We describe the clinical and biological features of ten patients with a survival
      superior to ten years (long survival), out of 175 patients diagnosed with Adult T
      cell Leukemia/Lymphoma (ATL) in Martinique (1983-2013). There were 5 lymphoma and
      5 chronic subtypes. Five of them (3 chronic, 2 lymphoma) had been treated with
      valproic acid (VA) for neurological disorders developed before or after ATL
      diagnosis, suggesting a beneficial role for VA as a histone deacetylase inhibitor
      (HDI) in ATL treatment. Total duration of uninterrupted VA treatment ranged from
      8 to 37 years. Overall, the 175 incident ATL cases presented with a median
      survival of 5.43 months. The five VA-treated (VA(+)) patients presented with
      longer survival compared to VA treatment-free patients (VA(-)). For chronic
      subtypes, survival periods were of 213 months for 3 VA(+) patients and of 33
      months for 11 VA(-) patients (p = 0.023). For lymphoma subtypes, survival periods
      were of 144 months for 2 VA(+) patients versus 6 months for 49 VA(-) patients (p
      = 0.0046). ATL cases with skin lesions, particularly lymphoma subtypes, had a
      longer survival (13.96 months) compared to those without skin lesions (6.06
      months, p = 0.002). Eight out of the 10 patients presenting with long survival
      had skin lesions. 

PMID- 26199761
TI  - A Technique for Removing Implant-Retained Denture: Direct Relining Complication.
AB  - The aim of this case report is to present a technique for removing the denture
      which locked to ball-attachment because of excessive hard relining resin material
      flows around the ball-attachment. An alternative method was used in the present
      case. A cylindrical resin was removed with a diamond bur at the level of matrix
      and by this way the matrix was removed safely. The advantage of the presented
      method is that it may be extended to other clinical situations when facing a
      similar complication for implant supported dentures and also that the technique
      is simple and does not require special equipment. 

PMID- 26199762
TI  - Surgical Management of Compound Odontoma Associated with Unerupted Tooth.
AB  - Odontomas represent the most common type of odontogenic benign jaws tumors among
      patients younger than 20 years of age. These tumors are composed of enamel,
      dentine, cementum, and pulp tissue. According to the World Health Organization
      classification, two distinct types of odontomas are acknowledged: complex and
      compound odontoma. In complex odontomas, all dental tissues are formed, but
      appeared without an organized structure. In compound odontomas, all dental
      tissues are arranged in numerous tooth-like structures known as denticles.
      Compound odontomas are often associated with impacted adjacent permanent teeth
      and their surgical removal represents the best therapeutic option. A case of a 20
      year-old male patient with a compound odontoma-associated of impacted maxillary
      canine is presented. A minimally invasive surgical technique is adopted to remove
      the least amount of bone tissue as far as possible. 

PMID- 26199763
TI  - The Enigma behind Pituitary and Sella Turcica.
AB  - The pituitary gland's role as a functional matrix for sella turcica has not been
      suggested in orthodontic literature. This paper is an attempt to correlate the
      role of pituitary gland in the development of sella turcica. A case report of
      dwarfism associated with hypopituitarism is presented to highlight the above
      hypothesis. 

PMID- 26199765
TI  - Scrotal Swelling as a Complication of Hydrochlorothiazide Induced Acute
      Pancreatitis.
AB  - Background. Scrotal swelling is a rare complication of acute pancreatitis with
      few reported cases in the literature. In this case report, we present a 59-year
      old male with hydrochlorothiazide induced pancreatitis who developed scrotal
      swelling. Case Presentation. A 59-year-old male presented to the emergency
      department with sharp epigastric abdominal pain that radiated to the back and
      chest. On physical examination, he had abdominal tenderness and distention with
      hypoactive bowel sounds. Computed tomography (CT) scan of the abdomen showed
      acute pancreatitis. The patient's condition deteriorated and he was admitted to
      the intensive care unit (ICU). After he improved and was transferred out of the
      ICU, the patient developed swelling of the scrotum and penis. Ultrasound (US) of
      the scrotum showed large hydrocele bilaterally with no varicoceles or testicular
      masses. Good blood flow was observed for both testicles. The swelling diminished
      over the next eight days with the addition of Lasix and the patient was
      discharged home in stable condition. Conclusion. Scrotal swelling is a rare
      complication of acute pancreatitis. It usually resolves spontaneously with
      conservative medical management such as diuretics and elevation of the legs. 

PMID- 26199764
TI  - A Case Report of Prilocaine-Induced Methemoglobinemia after Liposuction
      Procedure.
AB  - Prilocaine-induced methemoglobinemia is a rarely seen condition. In this paper, a
      case is presented with methemoglobinemia developed secondary to prilocaine use in
      a liposuction procedure, and the importance of this rarely seen condition is
      emphasized. A 20-year-old female patient presented with complaints of
      prostration, lassitude, shivering, shortness of breath, and cyanosis. It was
      learned that the patient underwent nearly 1000 mg prilocaine infiltration 8 hours
      priorly during a liposuction procedure. At admission, her blood pressure (130/80
      mmHg), pulse rate (140 bpm), body temperature (36 degrees C), and respiratory
      rate (40/min) were recorded. The patient had marked acrocyanosis. The arterial
      blood gas methemoglobin level was measured as 40%. The patient received oxygen
      therapy with a mask and was administered vitamin C in normal saline (500 mg tid),
      N-acetylcysteine (300 mg tid), and 50 mg 10% methylene blue in the intensive care
      unit of the internal medicine department. Methemoglobin level dropped down to 2%
      after her treatment with methylene blue and she was clinically cured and
      discharged 2 days later. Emergency service physicians should remember to consider
      methemoglobinemia when making a differential diagnosis between dyspnea and
      cyanosis developing after prilocaine infiltration performed for liposuctions in
      the adult age group. 

PMID- 26199767
TI  - Obstructing Colonic Mass: A Case of Recurrent Endometrial Cancer.
AB  - A 71-year-old female with a history of endometrial cancer presented to our
      hospital with bilateral lower quadrant abdominal pain, which had been worsening
      over the past two months. The pain was associated with constipation, pencil-thin
      stools, and a 60 lb weight loss. On physical examination, the patient had
      suprapubic and left lower quadrant abdominal tenderness. Contrast-enhanced CT
      scan revealed a 6 cm pelvic mass in the left lower quadrant. It was unclear if
      this mass was arising from the sigmoid colon or abutting it. A colonoscopy to
      further investigate the mass was pursued and this revealed a moderate 5 cm long
      stenosis in the sigmoid colon starting at 15 cm from the anal verge. The stenosis
      was not ulcerated but had a bluish/purplish hue to it circumferentially. Multiple
      biopsies were obtained from that area and these revealed architectural changes
      with mild fibrosis but no malignancy. The mass was further explored with CT
      guided fine needle aspiration. The results obtained were positive for cytokeratin
      7, CA-125, estrogen receptor protein, and PAX-8 confirming that the mass was
      endometrial in origin. 

PMID- 26199766
TI  - Characteristics of Small Bowel Polyps Detected in Cowden Syndrome by Capsule
      Endoscopy.
AB  - Cowden syndrome is an uncommon, autosomal dominant disease characterized by
      multiple hamartomas and hyperplastic lesions in the skin, mucous membrane, brain,
      breast, thyroid, and gastrointestinal tract. About 30% of Cowden syndrome cases
      are reportedly complicated by malignant diseases. Hamartomatous polyps occur
      throughout the gastrointestinal tract, the most common sites being the stomach,
      colon, esophagus, and duodenum. Small bowel polyps can occur in Cowden syndrome;
      however, they are difficult to detect by conventional examination, including
      double-contrast X-ray study. Here, we report three cases of Cowden syndrome with
      small bowel polyps, which were detected by capsule endoscopy. The small bowel
      polyps of Cowden syndrome frequently occur at the oral end of the small bowel,
      especially in the duodenum and jejunum, and their color is similar to that of the
      surrounding mucosa; additionally, the polyps are relatively small (2-5 mm).
      Capsule endoscopy is useful for detecting small bowel polyps in Cowden syndrome. 

PMID- 26199768
TI  - Extra-Axial Hematoma and Trimethoprim-Sulfamethoxazole Induced Aplastic Anemia:
      The Role of Hematological Diseases in Subdural and Epidural Hemorrhage.
AB  - Objective and Importance. To illustrate the development of spontaneous subdural
      hematoma secondary to aplastic anemia resulting from the administration of
      trimethoprim-sulfamethoxazole. This is the first report of trimethoprim
      sulfamethoxazole potentiating coagulopathy leading to any form of intracranial
      hematoma. Clinical Presentation. A 62-year-old female developed a bone marrow
      biopsy confirmed diagnosis of aplastic anemia secondary to administration of
      trimethoprim-sulfamethoxazole following a canine bite. She then developed a
      course of waxing and waning mental status combined with headache and balance
      related falls. CT imaging of the head illustrated a 3.7 cm * 6.6 mm left frontal
      subdural hematoma combined with a 7.0 mm * 1.7 cm left temporal epidural
      hematoma. Conclusion. Aplastic anemia is a rare complication of the
      administration of trimethoprim-sulfamethoxazole. Thrombocytopenia, regardless of
      cause, is a risk factor for the development of spontaneous subdural hematoma.
      Given the lack of a significant traumatic mechanism, this subset of subdural
      hematoma is more suitable to conservative management. 

PMID- 26199769
TI  - Stabilisation of Laryngeal AL Amyloidosis with Long Term Curcumin Therapy.
AB  - Multiple myeloma (MM), smoldering myeloma (SMM), and monoclonal gammopathy of
      undetermined significance (MGUS) represent a spectrum of plasma cell dyscrasias
      (PCDs). Immunoglobulin light chain amyloidosis (AL) falls within the spectrum of
      these diseases and has a mortality rate of more than 80% within 2 years of
      diagnosis. Curcumin, derived from turmeric, has been shown to have a clinical
      benefit in some patients with PCDs. In addition to a clinical benefit in these
      patients, curcumin has been found to have a strong affinity for fibrillar amyloid
      proteins. We thus administered curcumin to a patient with laryngeal amyloidosis
      and smoldering myeloma and found that the patient has shown a lack of progression
      of his disease for a period of five years. This is in keeping with our previous
      findings of clinical benefits of curcumin in patients with plasma cell
      dyscrasias. We recommend further evaluation of curcumin in patients with primary
      AL amyloidosis. 

PMID- 26199770
TI  - Compartmentalized Histoplasma capsulatum Infection of the Central Nervous System.
AB  - Background. Histoplasmosis is a common fungal infection in the southeastern, mid
      Atlantic, and central states; however, its presentation can be atypical. Case
      Presentation. We report a case of Histoplasma capsulatum infection presenting as
      slowly progressive weakness in the lower extremities, followed by the development
      of numbness below the midthoracic area, urinary incontinence, and slurred speech.
      Brain MRI showed leptomeningeal enhancement, predominantly linear, involving the
      basal cisterns, the brainstem, and spinal cord. Cerebrospinal fluid analysis
      showed lymphocytic pleocytosis. Discussion. CNS histoplasmosis is usually seen in
      patients with disseminated histoplasmosis. Isolated CNS histoplasmosis is rarely
      seen, especially in immunocompetent patients. Conclusions. Histoplasmosis should
      be considered in the differential diagnosis of patients experiencing slowly
      progressive neurological deficit. 

PMID- 26199771
TI  - Homozygosity for the E526V Mutation in Fibrinogen A Alpha-Chain Amyloidosis: The
      First Report.
AB  - Systemic hereditary amyloidoses are autosomal dominant diseases associated with
      mutations in genes encoding ten different proteins. The clinical phenotype has
      implications on therapeutic approach, but it is commonly variable and largely
      dependent on the type of mutation. Except for rare cases involving gelsolin or
      transthyretin, patients are heterozygous for the amyloidogenic variants. Here we
      describe the first patient identified worldwide as homozygous for a nephropathic
      amyloidosis, involving the fibrinogen variant associated with the fibrinogen
      alpha-chain E526V (p.Glu545Val) mutation. In 1989, a 44-year-old woman presented
      with hypertension, hepatosplenomegaly, nephrotic syndrome, and renal failure. She
      started hemodialysis in 1990 and 6 years later underwent isolated kidney
      transplantation from a deceased donor. Graft function and clinical status were
      unremarkable for 16 years, despite progressively increased left ventricular mass
      on echocardiography. In 2012, 4 months before death, she deteriorated rapidly
      with severe heart failure, precipitated by Clostridium difficile colitis and
      urosepsis. Affected family members developed nephropathy, on average, nearly
      three decades later, which may be explained by the gene dosage effects on the
      phenotype of E526V (p.Glu545Val) fibrinogen A alpha-chain amyloidosis. 

PMID- 26199772
TI  - Eosinophilic Granulomatosis with Polyangiitis Presenting as Acute Polyneuropathy
      Mimicking Guillain-Barre Syndrome.
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA) is a small-vessel vasculitis
      associated with antineutrophil cytoplasmic antibodies (ANCAs) which commonly
      affects the peripheral nervous system. A 38-year-old female with a history of
      asthma presented with a 2-week history of bilateral lower extremity paresthesias
      that progressed to symmetric ascending paralysis. Nerve conduction studies could
      not rule out Guillain-Barre syndrome (GBS) and plasmapheresis was considered. Her
      blood work revealed marked eosinophilia (>50%), she had purpuric lesions in her
      legs, and a head magnetic resonance image showed evidence of pansinusitis.
      Coupled with a history of asthma we suspected EGPA-associated neuropathy and
      started steroid treatment. The patient showed rapid and significant improvement.
      ANCAs were later reported positive. ANCA-associated vasculitides present most
      often as mononeuritis multiplex, but they can mimic GBS and should always be
      considered in the differential diagnosis, since the treatment strategies for
      these conditions are radically different. 

PMID- 26199773
TI  - Pregnancy and Vaginal Delivery after Sacrohysteropexy.
AB  - Pregnancy and birth after a Pelvic Organ Prolapse (POP) surgery is a rare
      condition and less is known about the method for delivery. A 31-year-old women
      with gravida 3 para 3 underwent abdominal sacrohysteropexy and transobturatuar
      tape (TOT) procedures for stage III prolapse who delivered via vaginal birth and
      showed no relapse. Sacrohysteropexy is a good option for women with POP who
      desire fertility with a long term follow-up period. 

PMID- 26199774
TI  - Postpartum Pyomyoma, a Rare Complication of Sepsis Associated with
      Chorioamnionitis and Massive Postpartum Haemorrhage Treated with an Intrauterine
      Balloon.
AB  - We report the successful treatment of a postpartum pyomyoma, a rare but serious
      complication of uterine leiomyomata in a 28-year-old primigravida. The patient
      was treated for an Escherichia Coli (E. Coli) urinary tract infection (UTI) at 16
      weeks of gestation. She had asymptomatic short cervical length on ultrasound scan
      at 20 weeks that was managed conservatively due to the presence of further UTI
      and received antibiotics. She was known to have a left sided intramural
      leiomyoma. She presented with abdominal pain and vaginal bleeding at 23(+1) weeks
      of gestation and the next day she had spontaneous vaginal delivery and collapsed
      with E. Coli septic shock, massive postpartum haemorrhage, and disseminated
      intravascular coagulation and was successfully treated with oxytocic drugs, a
      Rusch intrauterine balloon, and intravenous antibiotics. Eleven days postnatally
      she re-presented with systemic sepsis and was treated for retained products of
      conception. Sepsis persisted and investigations showed a postpartum pyomyoma that
      was initially managed with intravenous antibiotics to avoid surgery. Ultimately
      she required laparotomy, drainage of pyomyoma, and myomectomy. Postoperative
      recovery was good and the patient had a successful pregnancy two years later. 

PMID- 26199775
TI  - Antiangiogenic Therapies and Extracranial Metastasis in Glioblastoma: A Case
      Report and Review of the Literature.
AB  - We present a case report of a patient with glioblastoma multiforme (GBM)
      complicated by extracranial metastasis (ECM) whose survival of nearly four years
      surpassed the anticipated life expectancy given numerous negative prognostic
      factors including EGFRvIII-mutation, unmethylated MGMT promoter status, and ECM.
      Interestingly, while this patient suffered from locally aggressive disease with
      multiple intracranial recurrences, the proximal cause of death was progressive
      extracranial disease and complications related to pulmonary metastases. Herein,
      we review potential mechanisms of ECM with an emphasis upon glioblastoma
      molecular and genetic profiles and the potential implications of targeted agents
      such as bevacizumab. 

PMID- 26199776
TI  - Bilateral Iris Atrophy after the Femtosecond Assisted Laser In Situ
      Keratomileusis Surgery.
AB  - Purpose. To report an unknown complication of laser in situ keratomileusis
      (LASIK) surgery. Case Presentation. A 28-year-old female presented with
      photophobia and glare to our eye service. She stated in her medical history that
      she had undergone femtosecond assisted LASIK surgery in both eyes 15 months ago
      and her symptoms started just after this surgery. On admission, her best
      corrected visual acuity was 10/10 in both eyes. She had mydriatic pupils with no
      direct light reflex. Examination of the anterior segment revealed bilateral iris
      atrophy projecting within the LASIK ablation zone and a transillumination defect
      was remarkable on the slit lamp examination. Conclusion. We hypothesized that
      this condition may have been caused by the abnormally increased IOP that resulted
      in ischemia in the iris vascular plexus during the suction process of surgery. 

PMID- 26199777
TI  - Kingella kingae Causing Septic Arthritis of the Knee in an Immunocompetent Adult.
AB  - The bacterium Kingella kingae is a species of Gram-negative coccobacillus usually
      found in the oropharynx. This is an emerging pathogen reported to cause
      bacteraemia, endocarditis, and osteoarticular infections in children and
      endocarditis in the immunocompromised adult. However, there are few cases of
      isolated joint infections reported in the immunocompetent adult. Due to specific
      isolation techniques required, delay in diagnosis can compromise patient outcome.
      We report a rare case of septic arthritis of the knee in an immunocompetent adult
      caused by K. kingae. 

PMID- 26199778
TI  - Operative Management of OSAS in a Complex Case of Proteus Syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS) is a common disorder in childhood with
      high prevalence in syndromic subjects with craniofacial malformations. Proteus
      Syndrome (PS) is a rare hamartoneoplastic disorder associated with
      disproportionate and asymmetric overgrowth of body parts and hypertrophy or
      malformation of lymphatic tissues, such as palatine tonsils. We report a case of
      a 12-year-old boy diagnosed with Proteus Syndrome (PS) and suffering from OSAS
      due to asymmetric palatine tonsillar hypertrophy, treated with partial resection
      of left tonsil. To avoid the risk of a general anesthesia and remove only the
      obstructive portion of the palatine tonsil bipolar radiofrequency-induced
      thermotherapy (RFITT) under local anesthesia was performed. Recovery of the
      obstructive respiratory disease was obtained. To our knowledge, this is the first
      case reported in the literature of partial tonsillar resection performed in a
      patient with PS suffering from OSAS under local anesthesia. 

PMID- 26199779
TI  - Occult Breast Lobular Carcinoma with Numerous Circulating Tumor Cells in
      Peripheral Blood.
AB  - We experienced a very rare case of occult breast lobular carcinoma with numerous
      circulating tumor cells in peripheral blood. The diagnosis was very difficult
      because there were no symptoms of breast cancer and the preceding chief
      complaints such as general fatigue and weight loss or abnormality of peripheral
      blood findings were suggestive of a hematological disease. We could make a
      correct diagnosis of this case by checking the findings of complete blood count
      and bone marrow biopsy at the same time using immunohistochemistry. 

PMID- 26199780
TI  - 17-Year-Old Boy with Renal Failure and the Highest Reported Creatinine in
      Pediatric Literature.
AB  - The prevalence of chronic kidney disease (CKD) is on the rise and constitutes a
      major health burden across the world. Clinical presentations in early CKD are
      usually subtle. Awareness of the risk factors for CKD is important for early
      diagnosis and treatment to slow the progression of disease. We present a case
      report of a 17-year-old African American male who presented in a life threatening
      hypertensive emergency with renal failure and the highest reported serum
      creatinine in a pediatric patient. A brief discussion on CKD criteria,
      complications, and potential red flags for screening strategies is provided. 

PMID- 26199781
TI  - Anti-NMDA Receptor Encephalitis in a Patient with Previous Psychosis and
      Neurological Abnormalities: A Diagnostic Challenge.
AB  - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder
      characterized by IgG autoantibodies directed against the NR1 subunit of the NMDA
      glutamate receptor. Psychiatric symptoms are common and include psychosis, mania,
      depressed mood, aggression, and speech abnormalities. Neurological symptoms such
      as seizures, decreased responsiveness, dyskinesias, and other movement
      abnormalities and/or autonomic instability are frequently seen as well. We
      present the case of a woman who was followed up at our facility for over 14 years
      for the treatment of multiple neuropsychiatric symptoms. Initially, she presented
      with paresthesias, memory loss, and manic symptoms. Nine years later, she
      presented to our facility again, this time with left sided numbness, left eyelid
      droop, and word finding difficulties. Finally, five years later, she presented
      with manic symptoms, hallucinations, and memory impairment. During her
      hospitalization, she subsequently developed catatonic symptoms and seizures.
      During her stay, it was discovered that she was positive for anti-NMDA receptor
      antibodies and her symptoms responded well to appropriate therapy. This case
      demonstrates that it may be useful for clinicians to consider screening for anti
      NMDA receptor antibodies in long-term patients with neuropsychiatric symptoms
      that have not adequately responded to therapy. 

PMID- 26199782
TI  - Genetic or Psychogenic? A Case Study of "Folie a Quatre" Including Twins.
AB  - Shared psychotic disorder, characterized by shared delusion among two or more
      subjects (termed "Folie a deux," "trois," etc.), is often associated with strong
      religious beliefs or social isolation, factors creating strong psychological
      sympathy. Recently, we treated a rare familial case of "Folie a quatre" in
      central Tokyo without such influences. The proband was a schizophrenia patient
      and younger brother within monozygotic twins. Positive symptoms were
      "transmitted" to remaining family members, his elder brother, mother, and father
      father, in a relatively short period of three months. Although the
      pathophysiology of these positive symptoms (delusions and hallucinations) remains
      unclear, the transmission pattern suggests the primacy of social and
      environmental factors (and/or their interaction), while genetics appeared less
      influential in this "Folie a famille." Although undiagnosed psychoses in the
      whole family cannot be excluded, they did not share the other negative
      schizophrenia symptoms of the proband. A strong familial connection appeared to
      be the most important factor for the common delusion and hallucination. 

PMID- 26199783
TI  - Noncirrhotic Extrahepatic Portosystemic Shunt Causing Adult-Onset Encephalopathy
      Treated with Endovascular Closure.
AB  - A 54-year-old woman presented with a six-month history of episodic confusion and
      progressive ataxia. A comprehensive metabolic panel was notable for elevated
      values of alkaline phosphatase (161 U/L), total bilirubin (1.5 mg/dL), and serum
      ammonia of 300 umol/L (normal range 9-47). Hepatitis panel, relevant serological
      tests, tumor markers (CA-19-9, CEA), and urea cycle enzyme studies were
      unrevealing. Lactulose and rifaximin therapy failed to normalize serum ammonia
      levels. Imaging revealed a structural vascular abnormality communicating between
      an enlarged inferior mesenteric vein and the left renal vein, measuring 16 mm in
      greatest diameter. The diagnosis of congenital extrahepatic portosystemic shunt
      was made and endovascular shunt closure was performed using a 22 mm Amplatzer II
      vascular plug. Within a day, serum ammonia levels normalized. Lactulose and
      rifaximin were discontinued, and confusion and ataxia resolved. 

PMID- 26199784
TI  - Primary Dural Spinal Lymphoma Presentation of a Rare Spinal Tumor Case.
AB  - Background. Primary spinal dural lymphomas (PSDL) are tumors with characteristic
      histopathology of a lymphoma, which are completely in the spinal epidural space
      without any other systemic involvement. Extranodal primary lymphoma involving
      nervous system prefers thalamus/basal ganglia, periventricular region,
      cerebellum, eyes, meninges/dura, and cranial nerves or spinal cord. Rare spinal
      localization with acute spinal cord compression is worth attention. Case
      Presentation. A 48-year-old male presented with a several-month-long history of
      upper back pain. Lately, he had numbness and weakness at both lower extremities
      and was unable to walk for one week. A spinal MRI showed a thoracic lesion with
      cord compression at T2-T4 levels. The patient underwent surgical decompression,
      with his final histopathology showing diffuse large B-cell lymphoma. Systemic
      work-up was negative for nodal disease. Following surgery, he received
      radiotherapy combined with chemotherapy. He experienced a good outcome after four
      years. Conclusion. The upper thoracic cord is a rare location for primary spinal
      lesions/metastases, both of which prefer the lower thoracic and upper lumbar
      regions. In cases of progressive paraparesis, there should be immediate surgical
      intervention in the case of denovo disease, followed by combined radiotherapy and
      chemotherapy procedures. 

PMID- 26199785
TI  - Hemophagocytic Lymphohistiocytosis and Gastrointestinal Bleeding: What a Surgeon
      Should Know.
AB  - This paper presents to the surgical community an unusual and often ignored cause
      of gastrointestinal bleeding. Hemophagocytic syndrome or hemophagocytic
      lymphohistiocytosis (HLH) is a rare medical entity characterized by phagocytosis
      of red blood cells, leucocytes, platelets, and their precursors in the bone
      marrow by activated macrophages. When intestinal bleeding is present, the
      management is very challenging with extremely high mortality rates. Early
      diagnosis and treatment seem to be the most important factors for a successful
      outcome. We present two cases and review another 18 from the literature. 

PMID- 26199786
TI  - Magnetic Resonance Imaging of Non-ischemic Cardiomyopathies: A Pictorial Essay.
AB  - Non-ischemic cardiomyopathies are defined as either primary or secondary diseases
      of the myocardium resulting in cardiac dysfunction. While primary
      cardiomyopathies are confined to the heart and can be genetic or acquired,
      secondary cardiomyopathies show involvement of the heart as a manifestation of an
      underlying systemic disease including metabolic, inflammatory, granulomatous,
      infectious, or autoimmune entities. Non-ischemic cardiomyopathies are currently
      classified as hypertrophic, dilated, restrictive, or unclassifiable, including
      left ventricular non-compaction. Cardiovascular Magnetic Resonance Imaging (CMRI)
      not only has the capability to assess cardiac morphology and function, but also
      the ability to detect edema, hemorrhage, fibrosis, and intramyocardial deposits,
      providing a valuable imaging tool in the characterization of non-ischemic
      cardiomyopathies. This pictorial essay shows some of the most important non
      ischemic cardiomyopathies with an emphasis on magnetic resonance imaging
      features. 

PMID- 26199787
TI  - The Dens: Normal Development, Developmental Variants and Anomalies, and Traumatic
      Injuries.
AB  - Accurate interpretation of cervical spine imagining can be challenging,
      especially in children and the elderly. The biomechanics of the developing
      pediatric spine and age-related degenerative changes predispose these patient
      populations to injuries centered at the craniocervical junction. In addition,
      congenital anomalies are common in this region, especially those associated with
      the axis/dens, due to its complexity in terms of development compared to other
      vertebral levels. The most common congenital variations of the dens include the
      os odontoideum and a persistent ossiculum terminale. At times, it is necessary to
      distinguish normal development, developmental variants, and developmental
      anomalies from traumatic injuries in the setting of acute traumatic injury. Key
      imaging features are useful to differentiate between traumatic fractures and
      normal or variant anatomy acutely; however, the radiologist must first have a
      basic understanding of the spectrum of normal developmental anatomy and its
      anatomic variations in order to make an accurate assessment. This review article
      attempts to provide the basic framework required for accurate interpretation of
      cervical spine imaging with a focus on the dens, specifically covering the normal
      development and ossification of the dens, common congenital variants and their
      various imaging appearances, fracture classifications, imaging appearances, and
      treatment options. 

PMID- 26199788
TI  - Nontraumatic Fat Embolism Found Following Maternal Death after Cesarean Delivery.
AB  - Introduction Fat embolism is a rare form of nonthrombotic embolization. Limited
      literature exists regarding the diagnosis of fat embolism during the perinatal
      period. We present the first case of maternal death that resulted from
      nontraumatic fat embolization following Cesarean delivery. Case Description A 29
      year-old gravida 1 with a complex medical and surgical history underwent a
      primary Cesarean delivery at term. On postoperative day 2 the patient was found
      to be unresponsive. Despite resuscitative efforts, the patient succumbed. Autopsy
      findings were remarkable for diffuse pulmonary fat emboli. Furthermore, there was
      no histological evidence of either amniotic fluid embolism or thromboembolism.
      The primary cause of death was attributed to nontraumatic fat embolization.
      Discussion Multiple risk factors may have contributed to the development of
      nontraumatic fat embolization in our patient. Obstetricians should maintain a
      high level of suspicion for nontraumatic fat embolization in cases of maternal
      respiratory decompression and sudden maternal mortality. 

PMID- 26199789
TI  - Ankyloblepharon Filiforme Adnatum in a Newborn.
AB  - Ankyloblepharon filiforme adnatum (AFA) is a rare congenital anomaly consisting
      of a partial or complete fusion of the eyelid margins. It is usually an isolated
      and benign malformation but its presence should alert the neonatologist because
      it can be rarely associated to other important multisystemic disorders. We report
      a case of a newborn presenting with isolated AFA at birth, treated in the first
      day of life. 

PMID- 26199790
TI  - A Rapidly Growing Abdominal Mass: Desmoid Tumor in Pregnancy.
AB  - Background Desmoid tumors are benign soft tissue tumors that locally invade
      adjacent tissue. There is a paucity of reports describing the rapid growth of
      these tumors during pregnancy. Case A giant desmoid tumor arising from the left
      abdominal wall of a young female patient with rapid growth during pregnancy is
      described. Preoperative evaluation included ultrasonography and magnetic
      resonance imaging. Decision made by a multidisciplinary team was not to intervene
      before birth, and abdominal delivery at term was accomplished. Conclusion Desmoid
      tumors should be part of the differential diagnosis in an abdominal wall tumor of
      rapid growth during pregnancy. Future studies are needed for better understanding
      of the pathogenesis, diagnosis, and treatment of desmoid tumors in pregnant
      women. 

PMID- 26199791
TI  - Atrial Thrombus in a Neonate: A Diagnostic Challenge.
AB  - Introduction Left atrial thrombus is a rare finding in a neonate. In the previous
      literature, atrial thrombi have been associated with catheter placement or
      congenital heart disease in a preterm infant. Case We report the case of a full
      term neonate with no known risk factors found to have a left atrial thrombus. The
      neonate was born at 38 weeks' gestation to a 31-year-old female via cesarean
      section who was sent to the normal nursery. On postnatal day 5, the infant was
      noted to have low-to-medium level of oxygen saturations (~90%) and was
      transferred to the neonatal intensive care unit with an echocardiogram completed
      on postnatal day 6 demonstrating a mobile, pedunculated mass attached to the left
      atrial septum with an appearance concerning for atrial myxoma. The infant
      underwent surgical resection on postnatal day 8 and pathology revealed the mass
      to be a left atrial thrombus. Discussion The rare finding of an atrial thrombus
      in a neonate has previously been associated with central venous catheter
      placement or congenital heart disease. This case is unusual in that the patient
      had neither condition. Although echocardiogram findings appeared more consistent
      with atrial myxoma, final pathology revealed a left atrial thrombus.
      Additionally, hypercoagulability work-up for this neonate was largely negative.
      This report underscores the importance of identification, search for etiology,
      and prompt therapy to prevent potential catastrophic outcomes. 

PMID- 26199792
TI  - Familial Hemophagocytic Lymphohistiocytosis Presenting as Hydrops Fetalis.
AB  - Background Familial hemophagocytic lymphohistiocytosis (FLH) is an autosomal
      recessive disorder of immune regulation that leads to a hyperinflammatory
      syndrome. Fetal onset FHL is extremely rare and is considered to be the most
      severe form of FHL. Case We report a preterm case of FHL that presented as
      hydrops fetalis. The infant was treated with a chemotherapy regimen based on the
      HLH-2004 protocol from the third day of life. However, he had persistent
      cytopenia and died on the 18th day of life due to bacteremia. The detection of
      defective perforin expression in the patient's natural killer cells and mutations
      in the PRF1 gene resulted in a molecular diagnosis of FHL. Conclusion We suggest
      that early diagnosis and the development of an appropriate immunosuppressive
      strategy that can induce and maintain remission until hematopoietic stem cell
      transplantation can be performed are required to improve the outcomes of fetal
      onset FHL. 

PMID- 26199793
TI  - Stercoral Perforation of the Colon during Pregnancy: A Case Report and Review of
      the Literature.
AB  - Stercoral perforation of the colon, though rare, is associated with high
      mortality. Review of the literature identified only three prior cases reported
      during pregnancy. We report a case on a multiparous female presenting at 31 weeks
      of gestation with acute abdominal pain. Computed tomography suggested a sigmoid
      colon perforation. An urgent exploratory laparotomy was performed where feculent
      peritonitis and a stercoral perforation of the sigmoid colon was confirmed. A
      cesarean delivery and sigmoid colectomy with descending end colostomy was
      performed. While the newborn had an uncomplicated course, the mother developed an
      intra-abdominal abscess requiring operative management. 

PMID- 26199794
TI  - Rapid-Sequence Intubation in the Left-Lateral Tilt Position in a Pregnant Woman
      with Premature Placental Abruption Utilizing a Videolaryngoscope.
AB  - Case A 24-year-old pregnant woman was admitted to our hospital with decreased
      fetal heart rate. Obstetric examination revealed premature placental abruption;
      emergent caesarean section was planned under general anesthesia. On entering the
      operating room, the patient showed severe vital sign deterioration (blood
      pressure, 75/45 mm Hg; heart rate, 142 beats per minute). As left uterine
      displacement may worsen the premature placental abruption, the patient was placed
      in the left-lateral tilt position by rotating the operating table to release
      compression on the inferior vena cava by theuterus. To avoid circulatory
      collapse, rapid-sequence intubation was performed in this position. Tracheal
      intubation was performed with the Pentax-AWS Airwayscope (AWS videolaryngoscope,
      AWS; HOYA, Japan) to obtain a good laryngeal view and minimize stress from
      laryngoscopy. After sufficient oxygenation, 120 mg of thiopental was
      administered. A second anesthesiologist performed cricoid pressure and 50 mg of
      rocuronium was administered after confirming loss of consciousness. This was
      followed by insertion of the AWS with a thin intlock into the mouth. Tracheal
      intubation was performed uneventfully. Discussion Rapid-sequence intubation in
      the left-lateral tilted position with the AWS videolaryngoscope may be beneficial
      for pregnant women with vital sign deterioration. 

PMID- 26199795
TI  - A Case Report and Review of Postural Orthostatic Tachycardia Syndrome in
      Pregnancy.
AB  - Purpose Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic
      intolerance characterized by an increased heart rate upon transition from supine
      to standing, and head-up tilt without orthostatic hypotension. Its etiology is
      multifactorial, and no clear cause has been identified. Common symptoms include
      light-headedness, blurred vision, weakness, cognitive difficulties, and fatigue
      and are often accompanied by palpitations, shortness of breath, syncope, or
      gastrointestinal symptoms. Management includes volume expansion, physical counter
      maneuvers, and pharmacological agents such as fludrocortisone, midodrine,
      propranolol, and pyridostigmine. The course of POTS in pregnancy is variable and
      POTS has not been directly implicated in any adverse outcomes for the mother or
      fetus. Methods Two cases of POTS in pregnancy are presented, along with a review
      of the literature for reports of POTS in pregnancy. Results Along with our 2
      cases, 10 other case reports were identified and included. Conclusion The course
      of POTS in pregnancy is variable, and not directly linked to increase perinatal
      morbidity or mortality. Women can safely undergo regional anesthesia, and vaginal
      delivery with close monitoring of hemodynamic changes. 

PMID- 26199796
TI  - Extensive Fetal Congenital Subcutaneous Mixed Venous Lymphatic Lesion: Prenatal
      Diagnosis and Postnatal Management.
AB  - Vascular lesions may be categorized as proliferative tumors, such as hemangiomas,
      or nonproliferative malformations that include capillary, lymphatic, venous,
      arterial, or mixed lesions. Lymphatic malformations are benign localized
      congenital malformations of the lymphatic system. They may be microcystic or
      macrocystic lesions or a combination of both. The lesions may also be uniseptate
      or multiseptate, and are more commonly located in the head and neck or axillary
      region. Prenatal diagnosis is based on ultrasound and magnetic resonance imaging.
      Postnatal management largely depends on the size and location of the lesion. This
      is the first case report of prenatally diagnosed extensive subcutaneous
      macrocystic venous lymphatic malformation involving the fetal thorax, back,
      pelvis, and lower extremities. Prenatal course and postnatal management are
      described. This report will aid other specialists in the field of prenatal
      diagnosis and postnatal surgery in the evaluation and management of these
      patients. 

PMID- 26199797
TI  - Prenatal Diagnosis of Congenital Dermal Sinus.
AB  - Background Congenital dermal sinus (CDS) is an uncommon form of spinal
      dysraphism. Although postdelivery identification in the neonate is aided by
      several associated physical examination findings, establishing this diagnosis
      prenatally has proven to be elusive. Case Report We present a case of CDS where
      the prenatal findings at 20 weeks gestation led to the diagnosis, which was
      confirmed postnatally. The associated protrusion of fibrotic membranes through
      the sinus tract helped in the identification of this lesion prenatally, but
      created confusion with a more common type of lesion, an open neural tube defect.
      This is the first case report in the literature describing prenatal diagnosis of
      fetal CDS. Conclusion Prenatal diagnosis with postnatal confirmation of CDS leads
      to early intervention, better long-term outcomes, and lesser complications. 

PMID- 26199798
TI  - Congenital Systemic Fungus Infection in Twin Prematurity-A Case Report and
      Literature Review.
AB  - Congenital candidemia sepsis is a serious condition especially for the
      prematurity. Early recognition is always not the scenario and this leads to high
      morbidity and mortality. Twin pregnancy complicates the problems further. This
      report presents a case of congenital candidiasis in a twin preterm and
      literatures review of five twin pairs with the same scenario. In conclusion, for
      twin prematurity, if one is suspected to have invasive candidiasis, both of them
      should receive a full course of antifungal therapy through the intravenous route.

PMID- 26199799
TI  - Treatment of Sandifer Syndrome with an Amino-Acid-Based Formula.
AB  - Objective To study the presentation and treatment in two infants who presented
      with refractory Sandifer syndrome (SS). Study Design We retrospectively reviewed
      the cases of two infants who presented to our outpatient clinic with SS who were
      refractory to conventional treatment. Results We report two patients with
      refractory SS who responded to treatment with hypoallergenic formula. Conclusion
      It is important to consider a diagnosis of milk protein allergy responsive to
      hypoallergenic formula in patients with SS who are refractory to conventional
      antireflux treatment. 

PMID- 26199800
TI  - Surfactant Protein B Deficiency Caused by Homozygous C248X Mutation-A Case Report
      and Review of the Literature.
AB  - Objective Surfactant protein B (SP-B) deficiency is a rare autosomal recessive
      disorder that is usually rapidly fatal. The c.397delCinsGAA mutation (121ins2) in
      exon 4 is found in more than two-thirds of patients. Design We report on a fatal
      case of SP-B deficiency caused by a homozygous C248X mutation in exon 7 of the SP
      B gene. In addition, we provide an update of the current literature. The EMBASE,
      MEDLINE, and CINAHL databases were systematically searched to identify all papers
      published in the English and German literature on SP-B deficiency between 1989
      and 2013. Results SP-B deficiency is characterized by progressive hypoxemic
      respiratory failure generally in full-term infants. They present with symptoms of
      respiratory distress and hypoxemia; chest X-ray resembles hyaline membrane
      disease. Prenatal diagnosis is possible from amniotic fluid or chorionic villi
      sampling. Conclusion Thirty-four mutations have been published in the literature.
      Treatment options are scarce. Gene therapy is hoped to be an option in the
      future. 

PMID- 26199801
TI  - A Case Report and Literature Review of Midtrimester Termination of Pregnancy
      Complicated by Placenta Previa and Placenta Accreta.
AB  - Objective Concurrent placenta previa and placenta accreta increase the risk of
      massive obstetric hemorrhage. Despite extensive research on the management of
      placenta previa (including placenta accreta, increta, and percreta), the number
      and quality of previous studies are limited. We present a case of placenta
      accreta requiring an induced second-trimester abortion because of premature
      rupture of the membranes (PROM). Study Design Case report and review of the
      literature. Results A 41-year-old female presented at 20 weeks of gestation with
      placenta previa and PROM. Ultrasonography revealed placenta accreta with multiple
      placental lacunae. She then developed massive hemorrhaging just prior to a
      planned termination of pregnancy. We performed a hysterectomy with the intent of
      preserving life because of the failure of the placenta to detach and blood loss
      totaling 4,500 mL. Conclusion Previous studies suggest that second-trimester
      pregnancy terminations in cases of placenta previa which are not complicated with
      placenta accreta do not have a particularly high risk of hemorrhage. However,
      together with our case, the literature suggests that placenta previa complicated
      with placenta accreta presents a significant risk of hemorrhage both during
      delivery and intraoperatively. Further reports are needed to evaluate the most
      appropriate treatment options. 

PMID- 26199802
TI  - Case Series: Fetal Pulmonary Vein A-Wave Reversal: An Early Marker of Left-Sided
      Cardiac Anomalies?
AB  - Background Improvements in congenital heart disease (CHD) screening are needed
      based on the lack of sensitivity of current screening methods and the
      understanding that the early detection of certain CHDs may improve outcomes.
      Fetal venous circulation has caught medical attention, and two studies
      demonstrated that it is feasible to register pulmonary vein flow velocity
      waveforms (FVWs) during early gestation. Meanwhile, the latter study proposed
      pulmonary vein A-wave reversal as a marker of cardiac anomaly. Methods We report
      a series of six consecutive fetuses with confirmed cardiac anomalies that
      underwent first-trimester screening, including pulmonary vein FVWs, at our center
      during 2013. CHD was confirmed by late pregnancy echocardiography, and in three
      cases fetal autopsies were performed. Result/Discussion The ductus venosus (DV)
      and nuchal translucency (NT) predicted 50% of CHD cases, whereas the combination
      of markers identified 66.6% of CHD cases. When adding pulmonary vein assessment,
      the rate of detection rose to 83.3%. Total five of six cases of CHD had reversal
      of pulmonary vein A-wave during early pregnancy. The sixth case with CHD and
      nonreversal of A-wave was described as right ventricle hypoplasia with type 1
      tricuspid atresia and persistent ductus arteriosus. Conclusion This is the first
      series reporting pulmonary vein end-diastolic reversal as a CHD screening add-on
      during early pregnancy. The addition of pulmonary vein FVW assessment to the
      current CHD screening bundle could increase the rate detection of cardiac
      anomalies. This pilot study suggests that pulmonary vein end-diastolic flow
      reversal favors detection of left-sided CHD over the right-sided ones. 

PMID- 26199803
TI  - Hepatitis B Postexposure Prophylaxis in Preterm and Low-Birth-Weight Infants.
AB  - Objective Recommendations for immunoprophylaxis in low-birth-weight (LBW) infants
      born to hepatitis B surface antigen (HBsAg)-positive mothers vary. We
      successfully immunized an HBsAg-exposed infant (birth weight: 400 g) and
      performed a literature review on the outcome of postexposure immunoprophylaxis in
      HBsAg-exposed preterm and LBW infants. Methods By use of PubMed we identified
      articles relevant to the topic. Studies were included if the intended vaccine
      schedule was completed and follow-up data were reported. Results Antibody
      response was reported in 31 LBW infants (birth weight < 2,500 g) and 49 infants
      with gestational age of < 38 weeks. Low anti-HBs antibody levels (< 100 IU/L)
      were found in 9 (29%) of the 31 LBW infants. Overall, 2 of 20 (10%) preterm
      infants and 2 of 17 (12%) LBW were HBsAg-positive on follow-up. In one study,
      none of the 26 exposed very LBW infants became infected. Conclusion Due to
      heterogeneity in immunization schedules, lack of information on transmission
      rates, and the small number of included subjects, no firm conclusions can be
      drawn regarding the optimal postexposure prophylaxis in LBW infants. We propose
      that active and passive immunization at birth should be completed by three
      further active doses (0-1-2-12 month schedule) until further prospective studies
      are available. 

PMID- 26199805
TI  - Use of External Cephalic Version and Amnioreduction in the Delivery of a Fetal
      Demise with Macrocephaly Secondary to Massive Intracranial Teratoma.
AB  - Introduction Congenital intracranial tumors are rare and often incidentally
      diagnosed on routine ultrasound. We report a case of a fetal demise with a
      massive intracranial teratoma at 25 weeks of gestation and the management of her
      delivery in the setting of macrocephaly, breech presentation, and polyhydramnios.
      Case A 31-year-old G3P1011 woman at 25 weeks' gestation presented with a recent
      fetal demise and a fetal intracranial tumor first identified at 16 weeks'
      gestational age. The patient had declined termination of pregnancy. Biometry was
      consistent with 24 weeks' gestation, except for a head circumference of 394.4 mm
      consistent with 39 weeks' gestation. The fetus was in a breech presentation. An
      external cephalic version (ECV) was successfully performed under epidural
      anesthesia and an amnioreduction was then performed to stabilize the fetal
      position. Immediate induction of labor and vaginal delivery followed. Discussion
      ECV and amnioreduction may help facilitate delivery in cases of fetal demise
      complicated by macrocephaly, malpresentation, and polyhydramnios. 

PMID- 26199806
TI  - Fetal Isolated Anomalous Origin of Right Pulmonary Artery from Aorta.
AB  - The anomalous origin of a branch pulmonary artery from the aorta (AOPA) is
      characterized by the anomalous origin of one of the branch pulmonary arteries
      (PA) from the ascending aorta and a normal origin of the other PA from main PA.
      AOPA is an extremely rare cardiac malformation. Few studies have reported fetal
      anomalous origin of PA from aorta with other malformation. We report a case of
      isolated distal anomalous origin of the right PA from the aorta that was
      diagnosed by fetal echocardiography at 25 weeks' of gestation. Tracing the course
      of PA branches is important to make diagnosis. 

PMID- 26199804
TI  - Harlequin Color Change: Neonatal Case Series and Brief Literature Review.
AB  - First clinical report of Harlequin color change (HCC) phenomenon came in 1952
      from Neligan and Strang. Since then, HCC has been described in a fairly broad
      number of clinical reports involving neonates, infants, children, and adult
      patients. We here present a small case series of HCC occurring in neonates,
      pointing out three of the different possible presentations (hemifacial, patchy
      scattered across the whole body, and hemiscrotal) of this phenomenon. A brief
      discussion and literature review encompassing epidemiology, clinical features,
      physiopathology, associated conditions, and differential diagnoses of HCC is then
      presented. In most cases, HCC represents a benign, idiopathic, and rapidly
      autoresolutive phenomenon, with no need for treatment. Some drugs (especially
      anesthetics and prostaglandin E) are thought to enhance HCC expression through
      their influence on the capillary tone in the peripheral vascular bed; this effect
      is anyway promptly reversible with drug withdrawal. Only in rare circumstances,
      HCC may act as a clue for serious central nervous system disorders (e.g.,
      meningitis; hypothalamic, brain stem, or sympathetic nervous system lesions);
      anyway, in these rare occurrences HCC always represents an epiphenomenon of the
      disease, never acting as the sole sign of the underlying disorder. 

PMID- 26199807
TI  - 4th Cross-Cultural Health Care Conference: Collaborative and Multidisciplinary
      Interventions, January 16-17, 2015.

PMID- 26199830
TI  - Growth and morphological analysis of segmented AuAg alloy nanowires created by
      pulsed electrodeposition in ion-track etched membranes.
AB  - BACKGROUND: Multicomponent heterostructure nanowires and nanogaps are of great
      interest for applications in sensorics. Pulsed electrodeposition in ion-track
      etched polymer templates is a suitable method to synthesise segmented nanowires
      with segments consisting of two different types of materials. For a well
      controlled synthesis process, detailed analysis of the deposition parameters and
      the size-distribution of the segmented wires is crucial. RESULTS: The fabrication
      of electrodeposited AuAg alloy nanowires and segmented Au-rich/Ag-rich/Au-rich
      nanowires with controlled composition and segment length in ion-track etched
      polymer templates was developed. Detailed analysis by cyclic voltammetry in ion
      track membranes, energy-dispersive X-ray spectroscopy and scanning electron
      microscopy was performed to determine the dependency between the chosen potential
      and the segment composition. Additionally, we have dissolved the middle Ag-rich
      segments in order to create small nanogaps with controlled gap sizes. Annealing
      of the created structures allows us to influence their morphology. CONCLUSION:
      AuAg alloy nanowires, segmented wires and nanogaps with controlled composition
      and size can be synthesised by electrodeposition in membranes, and are ideal
      model systems for investigation of surface plasmons.

PMID- 26199831
TI  - High photocatalytic activity of V-doped SrTiO3 porous nanofibers produced from a
      combined electrospinning and thermal diffusion process.
AB  - In this letter, we report a novel V-doped SrTiO3 photocatalyst synthesized via
      electrospinning followed by a thermal diffusion process at low temperature. The
      morphological and crystalline structural investigations reveal not only that the
      V-doped SrTiO3 photocatalyst possesses a uniform, porous, fibrous structure, but
      also that some V(5+) ions are introduced into the SrTiO3 lattice. The
      photocatalytic capability of V-doped SrTiO3 porous nanofibers was evaluated
      through photodegrading methyl orange (MO) in aqueous solution under artificial UV
      vis light. The results indicated that V-doped SrTiO3 porous nanofibers have
      excellent catalytic efficiency. Furthermore, the excellent catalytic activity was
      maintained even after five cycle tests, indicating that they have outstanding
      photocatalytic endurance. It is suggested that the excellent photocatalytic
      performance of doped SrTiO3 nanofibers is possibly attributed to the V(5+) ion
      doping increasing the light utilization as well as to the outstanding porous
      features, the excellent component and structure stability. 

PMID- 26199832
TI  - Heterometal nanoparticles from Ru-based molecular clusters covalently anchored
      onto functionalized carbon nanotubes and nanofibers.
AB  - Heterometal clusters containing Ru and Au, Co and/or Pt are anchored onto carbon
      nanotubes and nanofibers functionalized with chelating phosphine groups. The
      cluster anchoring yield is related to the amount of phosphine groups available on
      the nanocarbon surface. The ligands of the anchored molecular species are then
      removed by gentle thermal treatment in order to form nanoparticles. In the case
      of Au-containing clusters, removal of gold atoms from the clusters and
      agglomeration leads to a bimodal distribution of nanoparticles at the nanocarbon
      surface. In the case of Ru-Pt species, anchoring occurs without reorganization
      through a ligand exchange mechanism. After thermal treatment, ultrasmall (1-3 nm)
      bimetal Ru-Pt nanoparticles are formed on the surface of the nanocarbons.
      Characterization by high resolution transmission electron microscopy (HRTEM) and
      high angle annular dark field scanning transmission electron microscopy (HAADF
      STEM) confirms their bimetal nature on the nanoscale. The obtained bimetal
      nanoparticles supported on nanocarbon were tested as catalysts in ammonia
      synthesis and are shown to be active at low temperature and atmospheric pressure
      with very low Ru loading. 

PMID- 26199833
TI  - Structural transitions in electron beam deposited Co-carbonyl suspended nanowires
      at high electrical current densities.
AB  - Suspended nanowires (SNWs) have been deposited from Co-carbonyl precursor
      (Co2(CO)8) by focused electron beam induced deposition (FEBID). The SNWs
      dimensions are about 30-50 nm in diameter and 600-850 nm in length. The as
      deposited material has a nanogranular structure of mixed face-centered cubic
      (FCC) and hexagonal close-packed (HCP) Co phases, and a composition of 80 atom %
      Co, 15 atom % O and 5 atom % C, as revealed by transmission electron microscopy
      (TEM) analysis and by energy-dispersive X-ray (EDX) spectroscopy, respectively.
      Current (I)-voltage (V) measurements with current densities up to 10(7) A/cm(2)
      determine different structural transitions in the SNWs, depending on the I-V
      history. A single measurement with a sudden current burst leads to a
      polycrystalline FCC Co structure extended over the whole wire. Repeated
      measurements at increasing currents produce wires with a split structure: one
      half is polycrystalline FCC Co and the other half is graphitized C. The breakdown
      current density is found at 2.1 * 10(7) A/cm(2). The role played by resistive
      heating and electromigration in these transitions is discussed. 

PMID- 26199834
TI  - PLGA nanoparticles as a platform for vitamin D-based cancer therapy.
AB  - Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were studied as drug delivery
      vehicles for calcitriol, the active form of vitamin D3. In vitro effects of
      calcitriol encapsulated in PLGA nanoparticles were evaluated with respect to free
      calcitriol on human pancreatic cell lines, S2-013 and hTERT-HPNE, and the lung
      cancer cell line A549. Encapsulated calcitriol retained its biological activity,
      reducing the cell growth. Cytotoxicity assays demonstrated that encapsulation of
      calcitriol enhanced its inhibitory effect on cell growth at a concentration of
      2.4 MUM for the S2-013 cells (91%) and for A549 cells (70%) comparared to the
      free calcitriol results. At this concentration the inhibitory effect on nontumor
      cells (hTERT-HPNE) decreased to 65%. This study highlights the ability of PLGA
      nanoparticles to deliver vitamin D3 into cancer cells, with major effects
      regarding cancer cell cycle arrest and major changes in the cell morphological
      features. 

PMID- 26199835
TI  - Influence of the shape and surface oxidation in the magnetization reversal of
      thin iron nanowires grown by focused electron beam induced deposition.
AB  - Iron nanostructures grown by focused electron beam induced deposition (FEBID) are
      promising for applications in magnetic sensing, storage and logic. Such
      applications require a precise design and determination of the coercive field (H
      C), which depends on the shape of the nanostructure. In the present work, we have
      used the Fe2(CO)9 precursor to grow iron nanowires by FEBID in the thickness
      range from 10 to 45 nm and width range from 50 to 500 nm. These nanowires exhibit
      an Fe content between 80 and 85%, thus giving a high ferromagnetic signal.
      Magneto-optical Kerr characterization indicates that H C decreases for increasing
      thickness and width, providing a route to control the magnetization reversal
      field through the modification of the nanowire dimensions. Transmission electron
      microscopy experiments indicate that these wires have a bell-type shape with a
      surface oxide layer of about 5 nm. Such features are decisive in the actual value
      of H C as micromagnetic simulations demonstrate. These results will help to make
      appropriate designs of magnetic nanowires grown by FEBID. 

PMID- 26199836
TI  - Nanomechanical humidity detection through porous alumina cantilevers.
AB  - We present here the behavior of the resonance frequency of porous anodic alumina
      cantilever arrays during water vapor adsorption and emphasize their possible use
      in the micromechanical sensing of humidity levels at least in the range of 10
      22%. The sensitivity of porous anodic aluminium oxide cantilevers (Deltaf/Deltam)
      and the humidity sensitivity equal about 56 Hz/pg and about 100 Hz/%,
      respectively. The approach presented here for the design of anodic alumina
      cantilever arrays by the combination of anodic oxidation and photolithography
      enables easy control over porosity, surface area, geometric and mechanical
      characteristics of the cantilever arrays for micromechanical sensing. 

PMID- 26199837
TI  - Natural and artificial binders of polyriboadenylic acid and their effect on RNA
      structure.
AB  - The employment of molecular tools with nucleic acid binding ability to
      specifically control crucial cellular functions represents an important
      scientific area at the border between biochemistry and pharmaceutical chemistry.
      In this review we describe several molecular systems of natural or artificial
      origin, which are able to bind polyriboadenylic acid (poly(rA)) both in its
      single-stranded or structured forms. Due to the fundamental role played by the
      poly(rA) tail in the maturation and stability of mRNA, as well as in the
      initiation of the translation process, compounds able to bind this RNA tract,
      influencing the mRNA fate, are of special interest for developing innovative
      biomedical strategies mainly in the field of anticancer therapy. 

PMID- 26199838
TI  - The Kirkendall effect and nanoscience: hollow nanospheres and nanotubes.
AB  - Hollow nanostructures are ranked among the top materials for applications in
      various modern technological areas including energy storage devices, catalyst,
      optics and sensors. The last years have witnessed increasing interest in the
      Kirkendall effect as a versatile route to fabricate hollow nanostructures with
      different shapes, compositions and functionalities. Although the conversion
      chemistry of nanostructures from solid to hollow has reached a very advanced
      maturity, there is still much to be discovered and learned on this effect. Here,
      the recent progress on the use of the Kirkendall effect to synthesize hollow
      nanospheres and nanotubes is reviewed with a special emphasis on the fundamental
      mechanisms occurring during such a conversion process. The discussion includes
      the oxidation of metal nanostructures (i.e., nanospheres and nanowires), which is
      an important process involving the Kirkendall effect. For nanospheres, the
      symmetrical and the asymmetrical mechanisms are both reviewed and compared on the
      basis of recent reports in the literature. For nanotubes, in addition to a
      summary of the conversion processes, the unusual effects observed in some
      particular cases (e.g., formation of segmented or bamboo-like nanotubes) are
      summarized and discussed. Finally, we conclude with a summary, where the
      prospective future direction of this research field is discussed. 

PMID- 26199839
TI  - Formation of substrate-based gold nanocage chains through dealloying with nitric
      acid.
AB  - Metal nanocages have raised great interest because of their new properties and
      wide applications. Here, we report on the use of galvanic replacement reactions
      to synthesize substrate-supported Ag-Au nanocages from silver templates
      electrodeposited on transparent indium tin oxide (ITO) film coated glass. The
      residual Ag in the composition was dealloyed with 10% nitric acid. It was found
      that chains of Au nanocages were formed on the substrate surface during
      dealloying. When the concentration of HNO3 increased to 20%, the structures of
      nanocages were damaged and formed crescent or semi-circular shapes. The transfer
      process on the substrate surface was discussed. 

PMID- 26199840
TI  - Alternative types of molecule-decorated atomic chains in Au-CO-Au single-molecule
      junctions.
AB  - We investigate the formation and evolution of Au-CO single-molecule break
      junctions. The conductance histogram exhibits two distinct molecular
      configurations, which are further investigated by a combined statistical
      analysis. According to conditional histogram and correlation analysis these
      molecular configurations show strong anticorrelations with each other and with
      pure Au monoatomic junctions and atomic chains. We identify molecular precursor
      configurations with somewhat higher conductance, which are formed prior to single
      molecule junctions. According to detailed length analysis two distinct types of
      molecule-affected chain-formation processes are observed, and we compare these
      results to former theoretical calculations considering bridge- and atop-type
      molecular configurations where the latter has reduced conductance due to
      destructive Fano interference. 

PMID- 26199841
TI  - Scalable, high performance, enzymatic cathodes based on nanoimprint lithography.
AB  - Here we detail high performance, enzymatic electrodes for oxygen bio
      electroreduction, which can be easily and reproducibly fabricated with industry
      scale throughput. Planar and nanostructured electrodes were built on
      biocompatible, flexible polymer sheets, while nanoimprint lithography was used
      for electrode nanostructuring. To the best of our knowledge, this is one of the
      first reports concerning the usage of nanoimprint lithography for amperometric
      bioelectronic devices. The enzyme (Myrothecium verrucaria bilirubin oxidase) was
      immobilised on planar (control) and artificially nanostructured, gold electrodes
      by direct physical adsorption. The detailed electrochemical investigation of
      bioelectrodes was performed and the following parameters were obtained: open
      circuit voltage of approximately 0.75 V, and maximum bio-electrocatalytic current
      densities of 18 uA/cm(2) and 58 uA/cm(2) in air-saturated buffers versus 48
      uA/cm(2) and 186 uA/cm(2) in oxygen-saturated buffers for planar and
      nanostructured electrodes, respectively. The half-deactivation times of planar
      and nanostructured biocathodes were measured to be 2 h and 14 h, respectively.
      The comparison of standard heterogeneous and bio-electrocatalytic rate constants
      showed that the improved bio-electrocatalytic performance of the nanostructured
      biocathodes compared to planar biodevices is due to the increased surface area of
      the nanostructured electrodes, whereas their improved operational stability is
      attributed to stabilisation of the enzyme inside nanocavities. 

PMID- 26199842
TI  - Thermal treatment of magnetite nanoparticles.
AB  - This paper presents the results of a thermal treatment process for magnetite
      nanoparticles in the temperature range of 50-500  degrees C. The tested magnetite
      nanoparticles were synthesized using three different methods that resulted in
      nanoparticles with different surface characteristics and crystallinity, which in
      turn, was reflected in their thermal durability. The particles were obtained by
      coprecipitation from Fe chlorides and decomposition of an Fe(acac)3 complex with
      and without a core-shell structure. Three types of ferrite nanoparticles were
      produced and their thermal stability properties were compared. In this study, two
      sets of unmodified magnetite nanoparticles were used where crystallinity was as
      determinant of the series. For the third type of particles, a Ag shell was added.
      By comparing the coated and uncoated particles, the influence of the metallic
      layer on the thermal stability of the nanoparticles was tested. Before and after
      heat treatment, the nanoparticles were examined using transmission electron
      microscopy, IR spectroscopy, differential scanning calorimetry, X-ray diffraction
      and Mossbauer spectroscopy. Based on the obtained results, it was observed that
      the fabrication methods determine, to some extent, the sensitivity of the
      nanoparticles to external factors. 

PMID- 26199843
TI  - Self-assembly of nanostructures and nanomaterials.

PMID- 26199844
TI  - Peptide-equipped tobacco mosaic virus templates for selective and controllable
      biomineral deposition.
AB  - The coating of regular-shaped, readily available nanorod biotemplates with
      inorganic compounds has attracted increasing interest during recent years. The
      goal is an effective, bioinspired fabrication of fiber-reinforced composites and
      robust, miniaturized technical devices. Major challenges in the synthesis of
      applicable mineralized nanorods lie in selectivity and adjustability of the
      inorganic material deposited on the biological, rod-shaped backbones, with
      respect to thickness and surface profile of the resulting coating, as well as the
      avoidance of aggregation into extended superstructures. Nanotubular tobacco
      mosaic virus (TMV) templates have proved particularly suitable towards this goal:
      Their multivalent protein coating can be modified by high-surface-density
      conjugation of peptides, inducing and governing silica deposition from precursor
      solutions in vitro. In this study, TMV has been equipped with mineralization
      directing peptides designed to yield silica coatings in a reliable and
      predictable manner via precipitation from tetraethoxysilane (TEOS) precursors.
      Three peptide groups were compared regarding their influence on silica
      polymerization: (i) two peptide variants with alternating basic and acidic
      residues, i.e. lysine-aspartic acid (KD) x motifs expected to act as charge-relay
      systems promoting TEOS hydrolysis and silica polymerization; (ii) a
      tetrahistidine-exposing polypeptide (CA4H4) known to induce silicification due to
      the positive charge of its clustered imidazole side chains; and (iii) two
      peptides with high ZnO binding affinity. Differential effects on the
      mineralization of the TMV surface were demonstrated, where a (KD) x charge-relay
      peptide (designed in this study) led to the most reproducible and selective
      silica deposition. A homogenous coating of the biotemplate and tight control of
      shell thickness were achieved. 

PMID- 26199845
TI  - Electron and heat transport in porphyrin-based single-molecule transistors with
      electro-burnt graphene electrodes.
AB  - We have studied the charge and thermal transport properties of a porphyrin-based
      single-molecule transistor with electro-burnt graphene electrodes (EBG) using the
      nonequilibrium Green's function method and density functional theory. The
      porphyrin-based molecule is bound to the EBG electrodes by planar aromatic anchor
      groups. Due to the efficient pi-pi overlap between the anchor groups and graphene
      and the location of frontier orbitals relative to the EBG Fermi energy, we
      predict HOMO-dominated transport. An on-off ratio as high as 150 is predicted for
      the device, which could be utilized with small gate voltages in the range of +/
      0.1 V. A positive thermopower of +280 MUV/K is predicted for the device at the
      theoretical Fermi energy. The sign of the thermopower could be changed by tuning
      the Fermi energy. By gating the junction and changing the Fermi energy by +10
      meV, this can be further enhanced to +475 MUV/K. Although the electrodes and
      molecule are symmetric, the junction itself can be asymmetric due to different
      binding configurations at the electrodes. This can lead to rectification in the
      current-voltage characteristic of the junction. 

PMID- 26199846
TI  - Enhanced fullerene-Au(111) coupling in (2?3 * 2?3)R30 degrees  superstructures
      with intermolecular interactions.
AB  - Disordered and uniform (2?3 * 2?3)R30 degrees  superstructures of fullerenes on
      the Au(111) surface have been studied using scanning tunneling microscopy and
      spectroscopy. It is shown that the deposition and growth process of a fullerene
      monolayer on the Au(111) surface determine the resulting superstructure. The
      supply of thermal energy is of importance for the activation of a Au vacancy
      forming process and thus, one criterion for the selection of the respective
      superstructure. However, here it is depicted that a vacancy-adatom pair can be
      formed even at room temperature. This latter process results in C60 molecules
      that appear slightly more bright in scanning tunnelling microscopy images and are
      identified in disordered (2?3 x 2?3)R30 degrees  superstructures based on a
      detailed structure analysis. In addition, these slightly more bright C60
      molecules form uniform (2?3 x 2?3)R30 degrees  superstructures, which exhibit
      intermolecular interactions, likely mediated by Au adatoms. Thus, vacancy-adatom
      pairs forming at room temperature directly affect the resulting C60
      superstructure. Differential conductivity spectra reveal a lifting of the
      degeneracy of the LUMO and LUMO+1 orbitals in the uniform (2?3 x 2?3)R30 degrees 
      superstructure and in addition, hybrid fullerene-Au(111) surface states suggest
      partly covalent interactions. 

PMID- 26199848
TI  - Using natural language processing techniques to inform research on
      nanotechnology.
AB  - Literature in the field of nanotechnology is exponentially increasing with more
      and more engineered nanomaterials being created, characterized, and tested for
      performance and safety. With the deluge of published data, there is a need for
      natural language processing approaches to semi-automate the cataloguing of
      engineered nanomaterials and their associated physico-chemical properties,
      performance, exposure scenarios, and biological effects. In this paper, we review
      the different informatics methods that have been applied to patent mining,
      nanomaterial/device characterization, nanomedicine, and environmental risk
      assessment. Nine natural language processing (NLP)-based tools were identified:
      NanoPort, NanoMapper, TechPerceptor, a Text Mining Framework, a Nanodevice
      Analyzer, a Clinical Trial Document Classifier, Nanotoxicity Searcher,
      NanoSifter, and NEIMiner. We conclude with recommendations for sharing NLP
      related tools through online repositories to broaden participation in
      nanoinformatics. 

PMID- 26199849
TI  - Improved atomic force microscopy cantilever performance by partial reflective
      coating.
AB  - Optical beam deflection systems are widely used in cantilever based atomic force
      microscopy (AFM). Most commercial cantilevers have a reflective metal coating on
      the detector side to increase the reflectivity in order to achieve a high signal
      on the photodiode. Although the reflective coating is usually much thinner than
      the cantilever, it can still significantly contribute to the damping of the
      cantilever, leading to a lower mechanical quality factor (Q-factor). In dynamic
      mode operation in high vacuum, a cantilever with a high Q-factor is desired in
      order to achieve a lower minimal detectable force. The reflective coating can
      also increase the low-frequency force noise. In contact mode and force
      spectroscopy, a cantilever with minimal low-frequency force noise is desirable.
      We present a study on cantilevers with a partial reflective coating on the
      detector side. For this study, soft (~0.01 N/m) and stiff (~28 N/m) rectangular
      cantilevers were used with a custom partial coating at the tip end of the
      cantilever. The Q-factor, the detection and the force noise of fully coated,
      partially coated and uncoated cantilevers are compared and force distance curves
      are shown. Our results show an improvement in low-frequency force noise and
      increased Q-factor for the partially coated cantilevers compared to fully coated
      ones while maintaining the same reflectivity, therefore making it possible to
      combine the best of both worlds. 

PMID- 26199847
TI  - DNA-melamine hybrid molecules: from self-assembly to nanostructures.
AB  - Single-stranded DNA-melamine hybrid molecular building blocks were synthesized
      using a phosphoramidation cross-coupling reaction with a zero linker approach.
      The self-assembly of the DNA-organic hybrid molecules was achieved by DNA
      hybridization. Following self-assembly, two distinct types of nanostructures in
      the form of linear chains and network arrays were observed. The morphology of the
      self-assembled nanostructures was found to depend on the number of DNA strands
      that were attached to a single melamine molecule. 

PMID- 26199851
TI  - Current-voltage characteristics of manganite-titanite perovskite junctions.
AB  - After a general introduction into the Shockley theory of current voltage (J-V)
      characteristics of inorganic and organic semiconductor junctions of different
      bandwidth, we apply the Shockley theory-based, one diode model to a new type of
      perovskite junctions with polaronic charge carriers. In particular, we studied
      manganite-titanate p-n heterojunctions made of n-doped SrTi1- y Nb y O3, y =
      0.002 and p-doped Pr1- x Ca x MnO3, x = 0.34 having a strongly correlated
      electron system. The diffusion length of the polaron carriers was analyzed by
      electron beam-induced current (EBIC) in a thin cross plane lamella of the
      junction. In the J-V characteristics, the polaronic nature of the charge carriers
      is exhibited mainly by the temperature dependence of the microscopic parameters,
      such as the hopping mobility of the series resistance and a colossal electro
      resistance (CER) effect in the parallel resistance. We conclude that a
      modification of the Shockley equation incorporating voltage-dependent microscopic
      polaron parameters is required. Specifically, the voltage dependence of the
      reverse saturation current density is analyzed and interpreted as a voltage
      dependent electron-polaron hole-polaron pair generation and separation at the
      interface. 

PMID- 26199852
TI  - Molecular materials - towards quantum properties.

PMID- 26199850
TI  - Atomic force microscopy as analytical tool to study physico-mechanical properties
      of intestinal cells.
AB  - The small intestine is a complex system that carries out various functions. The
      main function of enterocytes is absorption of nutrients, whereas membranous cells
      (M cells) are responsible for delivering antigens/foreign substances to the
      mucosal lymphoid tissues. However, to get a fundamental understanding of how
      cellular structures contribute to physiological processes, precise knowledge
      about surface morphologies, cytoskeleton organizations and biomechanical
      properties is necessary. Atomic force microscopy (AFM) was used here as a
      powerful tool to study surface topographies of Caco-2 cells and M cells.
      Furthermore, cell elasticity (i.e., the mechanical response of a cell on a tip
      indentation), was elucidated by force curve measurements. Besides elasticity,
      adhesion was evaluated by recording the attraction and repulsion forces between
      the tip and the cell surface. Organization of F-actin networks were investigated
      via phalloidin labeling and visualization was performed with confocal laser
      scanning fluorescence microscopy (CLSM) and scanning electron microscopy (SEM).
      The results of these various experimental techniques revealed significant
      differences in the cytoskeleton/microvilli arrangements and F-actin organization.
      Caco-2 cells displayed densely packed F-actin bundles covering the entire cell
      surface, indicating the formation of a well-differentiated brush border. In
      contrast, in M cells actins were arranged as short and/or truncated thin villi,
      only available at the cell edge. The elasticity of M cells was 1.7-fold higher
      compared to Caco-2 cells and increased significantly from the cell periphery to
      the nuclear region. Since elasticity can be directly linked to cell adhesion, M
      cells showed higher adhesion forces than Caco-2 cells. The combination of
      distinct experimental techniques shows that morphological differences between
      Caco-2 cells and M cells correlate with mechanical cell properties and provide
      useful information to understand physiological processes/mechanisms in the small
      intestine. 

PMID- 26199853
TI  - Thermal energy storage - overview and specific insight into nitrate salts for
      sensible and latent heat storage.
AB  - Thermal energy storage (TES) is capable to reduce the demand of conventional
      energy sources for two reasons: First, they prevent the mismatch between the
      energy supply and the power demand when generating electricity from renewable
      energy sources. Second, utilization of waste heat in industrial processes by
      thermal energy storage reduces the final energy consumption. This review focuses
      mainly on material aspects of alkali nitrate salts. They include thermal
      properties, thermal decomposition processes as well as a new method to develop
      optimized salt systems. 

PMID- 26199854
TI  - Transformations of PTCDA structures on rutile TiO2 induced by thermal annealing
      and intermolecular forces.
AB  - Transformations of molecular structures formed by perylene-3,4,9,10
      tetracarboxylic dianhydride (PTCDA) molecules on a rutile TiO2(110) surface are
      studied with low-temperature scanning tunnelling microscopy. We demonstrate that
      metastable molecular assemblies transform into differently ordered structures
      either due to additional energy provided by thermal annealing or when the
      influence of intermolecular forces is increased by the enlarged amount of
      deposited molecules. Proper adjustment of molecular coverage and substrate
      temperature during deposition allows for fabrication of desired assemblies.
      Differences between PTCDA/TiO2(110) and PTCDA/TiO2(011) systems obtained through
      identical experimental procedures are discussed. 

PMID- 26199855
TI  - Infection control: Knowledge and compliance among Saudi undergraduate dental
      students.
AB  - OBJECTIVE: This study aimed to assess the level of knowledge, attitudes, and
      practices regarding infection control procedures among undergraduate dental
      students. METHODS: This was a questionnaire-based cross-sectional survey. A self
      administered questionnaire consisting of questions on students' vaccination
      status as well as knowledge and attitudes regarding infection control was sent to
      600 undergraduate dental students in the fourth, fifth, and sixth year of the Al
      Farabi College for Dentistry and Nursing, Riyadh, Saudi Arabia. The collected
      data were analyzed using SPSS software. The significance level was set at P<0.05.
      RESULTS: The response rate was 85% (512 out of 600). While the vast majority of
      students (90%) had been vaccinated against hepatitis, only 37.4% have been
      assessed for anti-HBs. A total of 98.8% and 90.8% reported always wearing gloves
      and masks, respectively, during dental procedures. The use of protective eyewear
      was reported by only 29.2%. A significantly higher proportion of sixth-year
      students showed a positive attitude toward the treatment of patients with
      infectious diseases than other students of lower academic years. Approximately
      one-third of students reported having one or more occupational injuries while
      treating their patients. CONCLUSION: Although the students had good knowledge and
      attitudes regarding infection control, the compliance and practice levels
      regarding the same were low. Such findings highlight the necessity of continued
      infection-control education of Saudi dental students.

PMID- 26199856
TI  - Epstein-Barr virus association with peptic ulcer disease.
AB  - Background. Helicobacter pylori (HP) infection and nonsteroidal anti-inflammatory
      drugs (NSAID) use are considered the main risk to develop peptic ulcer disease
      (PUD). However, PUD also occurs in the absence of HP infection and/or NSAID use.
      Recently, we have found evidence that Epstein-Barr virus (EBV) reactivation
      increases the risk to develop premalignant and malignant gastric lesions.
      Objective. To study a possible association between EBV and PUD. Methods.
      Antibodies against an EBV reactivation antigen, HP, and the HP virulence factor
      CagA were measured in sera from 207 Mexican subjects, controls (healthy
      individuals, n = 129), and PUD patients (n = 78, 58 duodenal and 20 gastric
      ulcers). Statistical associations were estimated. Results. Duodenal PUD was
      significantly associated with high anti-EBV IgG titers (p = 0.022, OR = 2.5),
      while anti-EBV IgA was positively associated with gastric PUD (p = 0.002, OR =
      10.1). Conclusions. Our study suggests that EBV reactivation in gastric and
      duodenal epithelium increases the risk to develop PUD. 

PMID- 26199857
TI  - Evaluation of the selenotranscriptome expression in two hepatocellular carcinoma
      cell lines.
AB  - Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is
      still one of the most fatal cancers. Hence, it needs to identify always new
      putative markers to improve its diagnosis and prognosis. Since the selenium is
      able to fight the oxidative damage which is one of the major origins of cell
      damage as well as cancer, we have recently focused our attention on selenoprotein
      family and their involvement in HCC. In the present paper we have carried out a
      global analysis of the selenotranscriptome expression in HepG2 and Huh7 cells
      compared to the normal human hepatocytes by reverse transcription-qPCR (RT-qPCR).
      Our data showed that in both cells there are three downregulated (DIO1, DIO2, and
      SELO) and ten upregulated (GPX4, GPX7, SELK, SELM, SELN, SELT, SELV, SEP15,
      SEPW1, and TrxR1) genes. Additionally, interactomic studies were carried out to
      evaluate the ability of these down- and upregulated genes to interact between
      them as well as to identify putative HUB nodes representing the centers of
      correlation able to exercise a direct control over the coordinated genes. 

PMID- 26199858
TI  - Role of the IL-6 gene in the etiopathogenesis of idiopathic scoliosis.
AB  - Scoliotic human nuclei pulposi can respond to exogenous proinflammatory stimuli
      by secreting increased amounts of interleukin-6 (IL-6). The G/C polymorphism of
      the promoter region of IL-6 gene influences levels and functional activity of the
      IL-6 protein. We conducted a case-control study of eighty patients with
      idiopathic scoliosis (IS) and one hundred sixty healthy unrelated gender-matched
      controls trying to investigate the association between IS and the IL-6 promoter
      polymorphism at -174 position (rs1800795 G/C) in Bulgarian population. Molecular
      detection of the IL-6 genotypes was performed by amplification followed by
      restriction technology. The statistical analysis was performed by Pearson's chi
      squared test. Our case-control study revealed a statistically significant
      association between the IL-6 (-174 G/C) functional polymorphism and
      susceptibility to IS. In addition, a significant association between the IL-6 (
      174 G/C) polymorphism and curve severity was detected. IL-6 gene could be
      considered as susceptibility and modifying factor of idiopathic scoliosis. The
      identification of molecular markers with diagnostic and prognostic value could be
      useful for early detection of children at risk for the development of scoliosis
      and for prognosis of the risk for a rapid deformity progression. That would
      facilitate the therapy decisions and early stage treatment of the patient with
      the least invasive procedures. 

PMID- 26199859
TI  - Expression of five acetylcholine receptor subunit genes in Brugia malayi adult
      worms.
AB  - Acetylcholine receptors (AChRs) are required for body movement in parasitic
      nematodes and are targets of "classical" anthelmintic drugs such as levamisole
      and pyrantel and of newer drugs such as tribendimidine and derquantel. While
      neurotransmission explains the effects of these drugs on nematode movement, their
      effects on parasite reproduction are unexplained. The levamisole AChR type (L
      AChRs) in Caenorhabditis elegans is comprised of five subunits: Cel-UNC-29, Cel
      UNC-38, Cel-UNC-63, Cel-LEV-1 and Cel-LEV-8. The genome of the filarial parasite
      Brugia malayi contains nine AChRs subunits including orthologues of Cel-unc-29,
      Cel-unc-38, and Cel-unc-63. We performed in situ hybridization with RNA probes to
      localize the expression of five AChR genes (Bm1_35890-Bma-unc-29, Bm1_20330-Bma
      unc-38, Bm1_38195-Bma-unc-63, Bm1_48815-Bma-acr-26 and Bm1_40515-Bma-acr-12) in
      B. malayi adult worms. Four of these genes had similar expression patterns with
      signals in body muscle, developing embryos, spermatogonia, uterine wall adjacent
      to stretched microfilariae, wall of V as deferens, and lateral cord. Three L-AChR
      subunit genes (Bma-unc-29, Bma-unc-38 and Bma-unc-63) were expressed in body
      muscle, which is a known target of levamisole. Bma-acr-12 was co-expressed with
      these levamisole subunit genes in muscle, and this suggests that its protein
      product may form receptors with other alpha subunits. Bma-acr-26 was expressed in
      male muscle but not in female muscle. Strong expression signals of these genes in
      early embryos and gametes in uterus and testis suggest that AChRs may have a role
      in nervous system development of embryogenesis and spermatogenesis. This would be
      consistent with embryotoxic effects of drugs that target these receptors in
      filarial worms. Our data show that the expression of these receptor genes is
      tightly regulated with regard to localization in adult worms and developmental
      stage in embryos and gametes. These results may help to explain the broad effects
      of drugs that target AChRs in filarial worms. 

PMID- 26199860
TI  - Profiling the anti-protozoal activity of anti-cancer HDAC inhibitors against
      Plasmodium and Trypanosoma parasites.
AB  - Histone deacetylase (HDAC) enzymes work together with histone acetyltransferases
      (HATs) to reversibly acetylate both histone and non-histone proteins. As a
      result, these enzymes are involved in regulating chromatin structure and gene
      expression as well as other important cellular processes. HDACs are validated
      drug targets for some types of cancer, with four HDAC inhibitors clinically
      approved. However, they are also showing promise as novel drug targets for other
      indications, including malaria and other parasitic diseases. In this study the in
      vitro activity of four anti-cancer HDAC inhibitors was examined against parasites
      that cause malaria and trypanosomiasis. Three of these inhibitors,
      suberoylanilide hydroxamic acid (SAHA; vorinostat((r))), romidepsin
      (Istodax((r))) and belinostat (Beleodaq((r))), are clinically approved for the
      treatment of T-cell lymphoma, while the fourth, panobinostat, has recently been
      approved for combination therapy use in certain patients with multiple myeloma.
      All HDAC inhibitors were found to inhibit the growth of asexual-stage Plasmodium
      falciparum malaria parasites in the nanomolar range (IC50 10-200 nM), while only
      romidepsin was active at sub-MUM concentrations against bloodstream form
      Trypanosoma brucei brucei parasites (IC50 35 nM). The compounds were found to
      have some selectivity for malaria parasites compared with mammalian cells, but
      were not selective for trypanosome parasites versus mammalian cells. All
      compounds caused hyperacetylation of histone and non-histone proteins in P.
      falciparum asexual stage parasites and inhibited deacetylase activity in P.
      falciparum nuclear extracts in addition to recombinant PfHDAC1 activity. P.
      falciparum histone hyperacetylation data indicate that HDAC inhibitors may
      differentially affect the acetylation profiles of histone H3 and H4.

PMID- 26199861
TI  - Synergistic inhibition of Haemonchus contortus exsheathment by flavonoid monomers
      and condensed tannins.
AB  - This study investigated the separate and combined anthelmintic (AH) effects of
      different phenolic compounds, including condensed tannins and flavonoids, all of
      which are known to occur in willow leaves, a potentially valuable dry season
      feed. A range of contrasting model tannins, which span the whole range of willow
      tannins, were isolated from tilia flowers, goat willow leaves, black currant
      leaves and red currant leaves. All together, the tested compounds represented the
      major tannin types (procyanidins and prodelphinidins) and flavonoid types
      (flavonols, flavones and flavanones). The larval exsheathment inhibition assay
      (LEIA) was used to assess their in vitro effects on Haemonchus contortus third
      stage larvae. Arbutin, vanillic acid, and taxifolin proved to be ineffective
      whereas naringenin, quercetin and luteolin were highly effective at 250 MUM
      concentrations. Procyanidin (PC) tannins tended to be less active than
      prodelphinidin tannins (PD). Experiments with combinations of tannins and
      quercetin or luteolin revealed for the first time the existence of synergistic AH
      effects between tannins and flavonoid monomers. They also provided evidence that
      synergistic effects appear to occur at slightly lower concentrations of PC than
      PD. This suggests that the AH activity of condensed tannins can be significantly
      enhanced by the addition of quercetin or luteolin. This information may prove
      useful for plant breeding or selection and for designing optimal feed mixtures. 

PMID- 26199862
TI  - 2D DIGE proteomic analysis highlights delayed postnatal repression of alpha
      fetoprotein expression in homocystinuria model mice.
AB  - Cystathionine beta-synthase-deficient (Cbs (-/-)) mice, an animal model for
      homocystinuria, exhibit hepatic steatosis and juvenile semilethality via as yet
      unknown mechanisms. The plasma protein profile of Cbs (-/-) mice was investigated
      by proteomic analysis using two-dimensional difference gel electrophoresis and
      matrix-assisted laser desorption/ionization-time of flight/mass spectrometry. We
      found hyperaccumulation of alpha-fetoprotein (AFP) and downregulation of most
      other plasma proteins. AFP was highly expressed in fetal liver, but its
      expression declined dramatically via transcriptional repression after birth in
      both wild-type and Cbs (-/-) mice. However, the repression was delayed in Cbs (-/
      ) mice, causing high postnatal AFP levels, which may relate to transcriptional
      repression of most plasma proteins originating from liver and the observed
      hepatic dysfunction. 

PMID- 26199863
TI  - Small molecules inhibiting the nuclear localization of YAP/TAZ for
      chemotherapeutics and chemosensitizers against breast cancers.
AB  - YAP and TAZ oncoproteins confer malignancy and drug resistance to various cancer
      types. We screened for small molecules that inhibit the nuclear localization of
      YAP/TAZ. Dasatinib, statins and pazopanib inhibited the nuclear localization and
      target gene expression of YAP and TAZ. All three drugs induced phosphorylation of
      YAP and TAZ, and pazopanib induced proteasomal degradation of YAP/TAZ. The
      sensitivities to these drugs are correlated with dependence on YAP/TAZ in breast
      cancer cell lines. Combinations of these compounds with each other or with other
      anti-cancer drugs efficiently reduced cell proliferation of YAP/TAZ-dependent
      breast cancer cells. These results suggest that these drugs can be therapeutics
      and chemosensitizers for YAP/TAZ-dependent breast cancers. 

PMID- 26199864
TI  - Histone H3 Ser57 and Thr58 phosphorylation in the brain of 5XFAD mice.
AB  - Alzheimer's disease has been shown to have a global reduction in gene expression,
      called an epigenetic blockade, which may be regulated by histone post
      translational modifications. Histone H3 has been shown to be highly regulated by
      phosphorylation. We, therefore, chose H3 for investigation of phosphorylation of
      the core sites serine-57 (S57) and threonine-58 (T58). Hemispheres of brains from
      a mouse model of rapid amyloid deposition (5XFAD) were used for measurement of
      S57 and T58 phosphorylation. Multiple reaction monitoring (MRM) was used to
      measure the level of phosphorylation, which was normalized to a non-modified
      "housekeeping" peptide of H3. S57 phosphorylation was decreased by 40%, T58
      phosphorylation was decreased by 45%, and doubly phosphorylated S57pT58p was
      decreased by 30% in 5XFAD brain in comparison to C57BL/6J age- and sex-matched
      wild type controls. Amyloid-beta (Abeta) and amyloid precursor protein were also
      measured to confirm that 5XFAD mice produced high levels of Abeta. Decreased
      phosphorylation of these sites in close proximity to DNA may lead to
      stabilization of DNA-histone interactions and a condensed chromatin state,
      consistent with the epigenetic blockade associated with AD. Our findings of H3
      sites S57 and T58 exhibiting lower levels of phosphorylation in 5XFAD model
      compared to wild type control implicate these sites in the epigenetic blockade in
      neurodegeneration pathology. 

PMID- 26199866
TI  - Trichosporon faecale invasive infection in a patient with severe aplastic anemia:
      Efficacy of voriconazole and liposomal amphotericin B before neutrophil recovery.
AB  - We report a case of a 51-year old man with a severe aplastic anemia who developed
      an invasive trichosporonosis to Trichosporon faecale with fungemia and skin
      lesions during severe neutropenia. The treatment was successful before neutrophil
      recovery with a combination of voriconazole and liposomal amphotericin B. 

PMID- 26199865
TI  - Multiple binding modes of a small molecule to human Keap1 revealed by X-ray
      crystallography and molecular dynamics simulation.
AB  - Keap1 protein acts as a cellular sensor for oxidative stresses and regulates the
      transcription level of antioxidant genes through the ubiquitination of a
      corresponding transcription factor, Nrf2. A small molecule capable of binding to
      the Nrf2 interaction site of Keap1 could be a useful medicine. Here, we report
      two crystal structures, referred to as the soaking and the cocrystallization
      forms, of the Kelch domain of Keap1 with a small molecule, Ligand1. In these two
      forms, the Ligand1 molecule occupied the binding site of Keap1 so as to mimic the
      ETGE motif of Nrf2, although the mode of binding differed in the two forms.
      Because the Ligand1 molecule mediated the crystal packing in both the forms, the
      influence of crystal packing on the ligand binding was examined using a molecular
      dynamics (MD) simulation in aqueous conditions. In the MD structures from the
      soaking form, the ligand remained bound to Keap1 for over 20 ns, whereas the
      ligand tended to dissociate in the cocrystallization form. The MD structures
      could be classified into a few clusters that were related to but distinct from
      the crystal structures, indicating that the binding modes observed in crystals
      might be atypical of those in solution. However, the dominant ligand recognition
      residues in the crystal structures were commonly used in the MD structures to
      anchor the ligand. Therefore, the present structural information together with
      the MD simulation will be a useful basis for pharmaceutical drug development. 

PMID- 26199867
TI  - Primary invasive aspergillosis with disseminated intravascular coagulation as a
      presenting feature of non-Hodgkin's lymphoma.
AB  - Invasive aspergillosis (IA) is a life-threatening infection. IA is usually seen
      in severely immunocompromised patients. However, IA as a presenting feature of
      non-Hodgkin's lymphoma is rare. The patient we describe had no signs or symptoms
      of lymphoma prior to hospital admission. A. fumigatus was isolated from
      respiratory tract specimens on the day of admission and fungal elements were
      detected on autopsy. Isolation of Aspergillus in patients with severe sepsis
      should trigger a search haematological malignancy. 

PMID- 26199868
TI  - Systemic canine histoplasmosis: A case report from Ecuador.
AB  - Histoplasmosis is a zoonotic systemic mycosis caused by Histoplasma capsulatum.
      We report a case of a female canine, 4 years old, presenting multifocal
      lymphadenitis and skin and gingival lesions, in Ecuador. Based on cytological,
      histopathological, histochemical analyses, fungal culture and DNA sequencing of
      the ITS region of the fungus, the diagnosis confirmed the presence of H.
      capsulatum as the agent of infection. The treatment plan included ketoconazole
      with a satisfactory outcome. 

PMID- 26199869
TI  - Disrupted insula-based neural circuit organization and conflict interference in
      trauma-exposed youth.
AB  - Childhood trauma exposure is a potent risk factor for psychopathology. Emerging
      research suggests that aberrant saliency processing underlies the link between
      early trauma exposure and later cognitive and socioemotional deficits that are
      hallmark of several psychiatric disorders. Here, we examine brain and behavioral
      responses during a face categorization conflict task, and relate these to
      intrinsic connectivity of the salience network (SN). The results demonstrate a
      unique pattern of SN dysfunction in youth exposed to trauma (n = 14) relative to
      comparison youth (n = 19) matched on age, sex, IQ, and sociodemographic risk. We
      find that trauma-exposed youth are more susceptible to conflict interference and
      this correlates with higher fronto-insular responses during conflict. Resting
      state functional connectivity data collected in the same participants reveal
      increased connectivity of the insula to SN seed regions that is associated with
      diminished reward sensitivity, a critical risk/resilience trait following stress.
      In addition to altered intrinsic connectivity of the SN, we observed altered
      connectivity between the SN and default mode network (DMN) in trauma-exposed
      youth. These data uncover network-level disruptions in brain organization
      following one of the strongest predictors of illness, early life trauma, and
      demonstrate the relevance of observed neural effects for behavior and specific
      symptom dimensions. SN dysfunction may serve as a diathesis that contributes to
      illness and negative outcomes following childhood trauma. 

PMID- 26199870
TI  - The relative importance of imaging markers for the prediction of Alzheimer's
      disease dementia in mild cognitive impairment - Beyond classical regression.
AB  - Selecting a set of relevant markers to predict conversion from mild cognitive
      impairment (MCI) to Alzheimer's disease (AD) has become a challenging task given
      the wealth of regional pathologic information that can be extracted from
      multimodal imaging data. Here, we used regularized regression approaches with an
      elastic net penalty for best subset selection of multiregional information from
      AV45-PET, FDG-PET and volumetric MRI data to predict conversion from MCI to AD.
      The study sample consisted of 127 MCI subjects from ADNI-2 who had a clinical
      follow-up between 6 and 31 months. Additional analyses assessed the effect of
      partial volume correction on predictive performance of AV45- and FDG-PET data.
      Predictor variables were highly collinear within and across imaging modalities.
      Penalized Cox regression yielded more parsimonious prediction models compared to
      unpenalized Cox regression. Within single modalities, time to conversion was best
      predicted by increased AV45-PET signal in posterior medial and lateral cortical
      regions, decreased FDG-PET signal in medial temporal and temporobasal regions,
      and reduced gray matter volume in medial, basal, and lateral temporal regions.
      Logistic regression models reached up to 72% cross-validated accuracy for
      prediction of conversion status, which was comparable to cross-validated accuracy
      of non-linear support vector machine classification. Regularized regression
      outperformed unpenalized stepwise regression when number of parameters approached
      or exceeded the number of training cases. Partial volume correction had a
      negative effect on the predictive performance of AV45-PET, but slightly improved
      the predictive value of FDG-PET data. Penalized regression yielded more
      parsimonious models than unpenalized stepwise regression for the integration of
      multiregional and multimodal imaging information. The advantage of penalized
      regression was particularly strong with a high number of collinear predictors. 

PMID- 26199871
TI  - Parietal dysfunction during number processing in children with fetal alcohol
      spectrum disorders.
AB  - Number processing deficits are frequently seen in children prenatally exposed to
      alcohol. Although the parietal lobe, which is known to mediate several key
      aspects of number processing, has been shown to be structurally impaired in fetal
      alcohol spectrum disorders (FASD), effects on functional activity in this region
      during number processing have not previously been investigated. This fMRI study
      of 49 children examined differences in activation associated with prenatal
      alcohol exposure in five key parietal regions involved in number processing,
      using tasks involving simple addition and magnitude comparison. Despite generally
      similar behavioral performance, in both tasks greater prenatal alcohol exposure
      was related to less activation in an anterior section of the right horizontal
      intraparietal sulcus known to mediate mental representation and manipulation of
      quantity. Children with fetal alcohol syndrome and partial fetal alcohol syndrome
      appeared to compensate for this deficit by increased activation of the angular
      gyrus during the magnitude comparison task. 

PMID- 26199872
TI  - Handling changes in MRI acquisition parameters in modeling whole brain lesion
      volume and atrophy data in multiple sclerosis subjects: Comparison of linear
      mixed-effect models.
AB  - Magnetic resonance imaging (MRI) of the brain provides important outcome measures
      in the longitudinal evaluation of disease activity and progression in MS
      subjects. Two common measures derived from brain MRI scans are the brain
      parenchymal fraction (BPF) and T2 hyperintense lesion volume (T2LV), and these
      measures are routinely assessed longitudinally in clinical trials and
      observational studies. When measuring each outcome longitudinally, observed
      changes may be potentially confounded by variability in MRI acquisition
      parameters between scans. In order to accurately model longitudinal change, the
      acquisition parameters should thus be considered in statistical models. In this
      paper, several models for including protocol as well as individual MRI
      acquisition parameters in linear mixed models were compared using a large dataset
      of 3453 longitudinal MRI scans from 1341 subjects enrolled in the CLIMB study,
      and model fit indices were compared across the models. The model that best
      explained the variance in BPF data was a random intercept and random slope with
      protocol specific residual variance along with the following fixed-effects:
      baseline age, baseline disease duration, protocol and study time. The model that
      best explained the variance in T2LV was a random intercept and random slope along
      with the following fixed-effects: baseline age, baseline disease duration,
      protocol and study time. In light of these findings, future studies pertaining to
      BPF and T2LV outcomes should carefully account for the protocol factors within
      longitudinal models to ensure that the disease trajectory of MS subjects can be
      assessed more accurately. 

PMID- 26199873
TI  - Increases in frontostriatal connectivity are associated with response to
      dorsomedial repetitive transcranial magnetic stimulation in refractory
      binge/purge behaviors.
AB  - BACKGROUND: Conventional treatments for eating disorders are associated with poor
      response rates and frequent relapse. Novel treatments are needed, in combination
      with markers to characterize and predict treatment response. Here, resting-state
      functional magnetic resonance imaging (rs-fMRI) was used to identify predictors
      and correlates of response to repetitive transcranial magnetic stimulation (rTMS)
      of the dorsomedial prefrontal cortex (dmPFC) at 10 Hz for eating disorders with
      refractory binge/purge symptomatology. METHODS: 28 subjects with anorexia
      nervosa, binge-purge subtype or bulimia nervosa underwent 20-30 sessions of 10 Hz
      dmPFC rTMS. rs-fMRI data were collected before and after rTMS. Subjects were
      stratified into responder and nonresponder groups using a criterion of >=50%
      reduction in weekly binge/purge frequency. Neural predictors and correlates of
      response were identified using seed-based functional connectivity (FC), using the
      dmPFC and adjacent dorsal anterior cingulate cortex (dACC) as regions of
      interest. RESULTS: 16 of 28 subjects met response criteria. Treatment responders
      had lower baseline FC from dmPFC to lateral orbitofrontal cortex and right
      posterior insula, and from dACC to right posterior insula and hippocampus.
      Responders had low baseline FC from the dACC to the ventral striatum and anterior
      insula; this connectivity increased over treatment. However, in nonresponders,
      frontostriatal FC was high at baseline, and dmPFC-rTMS suppressed FC in
      association with symptomatic worsening. CONCLUSIONS: Enhanced frontostriatal
      connectivity was associated with responders to dmPFC-rTMS for binge/purge
      behavior. rTMS caused paradoxical suppression of frontostriatal connectivity in
      nonresponders. rs-fMRI could prove critical for optimizing stimulation parameters
      in a future sham-controlled trial of rTMS in disordered eating.

PMID- 26199875
TI  - Tracking transparent monogenean parasites on fish from infection to maturity.
AB  - The infection dynamics and distribution of the ectoparasitic fish monogenean
      Neobenedenia sp. (Monogenea: Capsalidae) throughout its development was examined
      on barramundi, Lates calcarifer (Bloch) (Latidae), by labelling transparent,
      ciliated larvae (oncomiracidia) with a fluorescent dye. Replicate fish were each
      exposed to approximately 50 fluorescent oncomiracidia and then examined for
      parasites using an epifluorescence stereomicroscope at 10 time intervals post
      exposure (15, 30, 60, 120 min, 24, 48 h, four, eight, 12, and 16 days).
      Fluorescent labelling revealed that parasites attached underneath and on the
      surface of the scales of host fish. Parasite infection success was 20% within 15
      min, and peaked at 93% two days post-exposure, before gradually declining between
      four and sixteen days. Differences in parasite distribution on L. calcarifer over
      time provided strong evidence that Neobenedenia sp. larvae settled
      opportunistically and then migrated to specific microhabitats. Parasites
      initially attached (<24 h) in greater mean numbers on the body surface (13 +/-
      1.5) compared to the fins (4 +/- 0.42) and head region (2 +/- 0.41). Once larvae
      recruitment had ceased (48 h), there were significantly higher mean post-larvae
      counts on the head (5 +/- 3.4) and fins (12 +/- 3) compared to previous time
      intervals. Neobenedenia sp. aggregated on the eyes, fins, and dorsal and ventral
      extremities on the main body. As parasites neared sexual maturity, there was a
      marked aggregation on the fins (22 +/- 2.35) compared to the head (4 +/- 0.97)
      and body (9 +/- 1.33), indicating that Neobenedenia sp. may form mating
      aggregations. 

PMID- 26199876
TI  - Letter from the Editor.

PMID- 26199874
TI  - Increased resting-state functional connectivity of visual- and cognitive-control
      brain networks after training in children with reading difficulties.
AB  - The Reading Acceleration Program, a computerized reading-training program,
      increases activation in neural circuits related to reading. We examined the
      effect of the training on the functional connectivity between independent
      components related to visual processing, executive functions, attention, memory,
      and language during rest after the training. Children 8-12 years old with reading
      difficulties and typical readers participated in the study. Behavioral testing
      and functional magnetic resonance imaging were performed before and after the
      training. Imaging data were analyzed using an independent component analysis
      approach. After training, both reading groups showed increased single-word
      contextual reading and reading comprehension scores. Greater positive
      correlations between the visual-processing component and the executive functions,
      attention, memory, or language components were found after training in children
      with reading difficulties. Training-related increases in connectivity between the
      visual and attention components and between the visual and executive function
      components were positively correlated with increased word reading and reading
      comprehension, respectively. Our findings suggest that the effect of the Reading
      Acceleration Program on basic cognitive domains can be detected even in the
      absence of an ongoing reading task. 

PMID- 26199877
TI  - Negative Pressure Wound Therapy With Instillation (NPWTi) Better Reduces Post
      debridement Bioburden in Chronically Infected Lower Extremity Wounds Than NPWT
      Alone.
AB  - OBJECTIVE: An overabundance of bacteria in the chronic wound plays a significant
      role in the decreased ability for primary closure. One means of decreasing the
      bioburden in a wound is to operatively debride the wound for wound bed
      optimization prior to application of other therapy, such as Negative Pressure
      Wound Therapy (NPWT). We undertook a prospective pilot study to assess the
      efficacy of wound bed preparation for a standard algorithm (sharp surgical
      debridement followed by NPWT) versus one employing sharp surgical debridement
      followed by Negative Pressure Wound Therapy with Instillation (NPWTi). METHODS:
      Thirteen patients, corresponding to 16 chronic lower leg and foot wounds were
      taken to the operating room for debridement. The patients were sequentially
      enrolled in 2 treatment groups: the first receiving treatment with operative
      debridement followed by 1 week of NPWT with the instillation of quarter strength
      bleach solution; the other receiving a standard algorithm consisting of operative
      debridement and 1 week of NPWT. Quantitative cultures were taken pre-operatively
      after sterile preparation and draping of the wound site (POD # 0, pre-op), post
      operatively once debridement was completed (POD # 0, post-op), and on post
      operative day 7 after operative debridement (POD # 7, post-op). RESULTS: After
      operative debridement (post-operative day 0) there was a mean of 3 (+/-1) types
      of bacteria per wound. The mean CFU/gram tissue culture was statistically greater
      - 3.7 * 10(6) (+/-4 * 10(6)) in the NPWTi group, while in the standard group
      (NPWT) the mean was 1.8 * 10(6) (+/-2.36 * 10(6)) CFU/gram tissue culture (p =
      0.016); at the end of therapy there was no statistical difference between the two
      groups (p = 0.44). Wounds treated with NPWTi had a mean of 2.6 * 10(5) (+/-3 *
      10(5)) CFU/gram of tissue culture while wounds treated with NPWT had a mean of
      2.79 * 10(6) (+/-3.18 * 10(6)) CFU/gram of tissue culture (p = 0.43). The mean
      absolute reduction in bacteria for the NPWTi group was 10.6 * 10(6) bacteria per
      gram of tissue while there was a mean absolute increase in bacteria for the NPWT
      group of 28.7 * 10(6) bacteria per gram of tissue, therefore there was a
      statistically significant reduction in the absolute bioburden in those wounds
      treated with NPWTi (p = 0.016). CONCLUSION: It has long been realized that NPWT
      does not make its greatest impact by bioburden reduction. Other work has
      demonstrated that debridement alone does not reduce wound bioburden by more than
      1 Log. Wounds treated with NPWTi (in this case with quarter strength bleach
      instillation solution) had a statistically significant reduction in bioburden,
      while wounds treated with NPWT had an increase in bioburden over the 7 days.

PMID- 26199878
TI  - Pitfalls of Intralesional Ozone Injection in Diabetic Foot Ulcers: A Case Study.
AB  - Although the history of ozone therapy dates back to the 19th century, its use has
      shown a rapid growth of interest in recent decades. Intralesional ozone injection
      is seldom performed and its safety has not yet been reliably assessed for the
      treatment of diabetic foot wounds. Herein, we describe a diabetic patient who
      developed severe foot necrosis and infection after receiving intralesional ozone
      injections for a non-healing wound. 

PMID- 26199880
TI  - Advanced Skin Care - A Novel Ingredient.
AB  - The skin provides the human body with protection and a major barrier to
      environmental assault. Caring for skin is sometimes an afterthought. In other
      words, if something isn't broken, don't fix it. However, in the case of the
      integument, nothing could be further from the truth. Intact skin is paramount to
      health and well-being. This article will review skin care, specifically, advanced
      skin care, uncovering novel ingredients, and their importance for prevention and
      treatment as well as delving into the caring for the skin from the outside in. 

PMID- 26199879
TI  - Factors That Impair Wound Healing.
AB  - The body's response to tissue injury in a healthy individual is an intricate,
      sequential physiologic process that results in timely healing with full re
      epithelialization, resolution of drainage, and return of function to the affected
      tissue. Chronic wounds, however, do not follow this sequence of events and can
      challenge the most experienced clinician if the underlying factors that are
      impairing wound healing are not identified. The purpose of this article is to
      present recent information about factors that impair wound healing with the
      underlying pathophysiological mechanism that interferes with the response to
      tissue injury. These factors include co-morbidities (diabetes, obesity, protein
      energy malnutrition), medications (steroids, non-steroidal anti-inflammatory
      drugs or NSAIDs, anti-rejection medications), oncology interventions (radiation,
      chemotherapy), and life style habits (smoking, alcohol abuse). Successful
      treatment of any chronic wound depends upon identification and management of the
      factors for each individual. 

PMID- 26199881
TI  - Letter from the Editor.

PMID- 26199882
TI  - Wound Healing in Patients With Impaired Kidney Function.
AB  - Renal impairment has long been known to affect wound healing. However,
      information on differences in the spectrum of wound healing depending on the type
      of renal insufficiency is limited. Acute kidney injury (AKI) may be observed with
      different wound types. On one hand, it follows acute traumatic conditions such as
      crush injury, burns, and post-surgical wounds, and on the other hand, it arises
      as simultaneous targeting of skin and kidneys by autoimmune-mediated vasculitis.
      Chronic kidney disease (CKD) and end-stage renal disease (ESRD) often occur in
      older people, who have limited physical mobility and predisposition for
      developing pressure-related wounds. The common risk factors for poor wound
      healing, generally observed in patients with CKD and ESRD, include poorly
      controlled diabetes mellitus, neuropathy, peripheral vascular disease, chronic
      venous insufficiency, and aging. ESRD patients have a unique spectrum of wounds
      related to impaired calcium-phosphorus metabolism, including calciphylaxis, in
      addition to having the risk factors presented by CKD patients. Overall, there is
      a wide range of uremic toxins: they may affect local mechanisms of wound healing
      and also adversely affect the functioning of multiple systems. In the present
      literature review, we discuss the association between different types of renal
      impairments and their effects on wound healing and examine this association from
      different aspects related to the management of wounds in renal impairment
      patients. 

PMID- 26199883
TI  - Use of a Novel Two-layer Bandage in the Treatment of Chronic Venous Hypertension.
AB  - Since the development of Unna boot therapies, there has been development in newer
      technologies for venous compression syndromes and chronic venous hypertension.
      Chronic lower extremity venous insufficiency results in venous stasis, edema and
      hypercongestion of the lower extremities. Given the breadth of potential uses,
      the goal of this study was to retrospectively compile and analyze the clinical
      application and effectiveness of a 2-layer zinc-impregnated foam Unna boot
      bandage (Andover Healthcare, Salisbury, MA) in patients with lower extremity
      swelling with or without wounds treated by a single physician and monitored for
      12 weeks post-application in the outpatient setting. In patients with complex
      comorbidities, the use of this new foam-impregnated multi-layer compression Unna
      boot shows efficacy in reduction of edema and wound size within 12 weeks. This
      newer therapy shows extensive promise in the ability to keep patients adherent to
      treatment regimens with higher rates of success. 

PMID- 26199884
TI  - The Use of Hyperbaric Oxygen Therapy in the Treatment of Non-healing Ulcers
      Secondary to Graft-versus-host Disease.
AB  - We present the case of a 69 year-old gentleman with non-healing ulcers of the
      bilateral medial malleoli as a result of graft-versus-host disease (GvHD). The
      patient discussed was diagnosed with stage IV mantle cell lymphoma. Over the
      course of 4 years the patient was treated with autologous stem cell transplant,
      later reduced-intensity allogeneic stem cell transplant, and finally donor
      lymphocyte infusion due to recurrence. Following these therapies, the patient
      developed extensive GvHD that resulted in bilateral non-healing ulcers of the
      medial malleoli. The patient was seen in the wound care center, and his ulcers
      were treated with standard care that included off-loading, minor outpatient
      debridement, macrovascular assessment, and local moist wound healing. Despite
      this care, the ulcers failed to heal over a 6 month period. The patient underwent
      adjunctive hyperbaric oxygen therapy (HBO). He healed both ulcers within a month
      of completing HBO. It is our goal to discuss the pathophysiologic mechanism of
      non-healing wounds in the setting of GvHD and discuss the potential role of HBO
      in their treatment. 

PMID- 26199885
TI  - Treatment of Burn Wound Infection Using Ultraviolet Light: A Case Report.
AB  - A 9 year old girl presented to us with complaints of fever and pain in burn
      wounds with deteriorating health for one month. According to Lund and Broder's
      chart, burns spanned the posterior trunk (13%), right arm (1.5%), left arm
      (1.5%), and buttocks (2.5%). The wounds showed improper healing. She had
      previously underwent split-thickness skin grafting, using skin harvests from
      thighs and antimicrobial therapy with vancomycin, fluconazole and colomycin with
      limited clinical improvement. Analgesia was administered. Blood cultures and
      tissue cultures from the burns indicated polymicrobial wound infection and
      sepsis, including methicillin resistant Staphylococcus aureus, Klebsiella
      pneumoniae and Pseudomonas aeruginosa. Despite broad-spectrum antibiotics, fever
      persisted and condition deteriorated. Antifungals were also administered with no
      clinical improvement. Eventually another split-thickness skin grafting was done
      to provide fresh grafts. In due course, ultraviolet light exposure, of wavelength
      32-40 nm/W/cm(2), was considered for treatment. In prone position, the wounds
      were exposed to ultraviolet phototherapy 6-8 h daily for 8 days. Eventually,
      wound healing and sepsis improved. Antibiotics were optimized and high protein
      diet was started. Eventually the wounds showed fresh margins and visible signs of
      healing. With remarkable clinical improvement and no further fever spikes, the
      patient was eventually discharged. She was advised to shower regularly, apply
      bandages with acetic acid. On her last outpatient follow up, 2 weeks after
      discharge, she was doing well, with no complaints of pain or fever. Examination
      of burns showed clean wounds, with clear margins and good graft uptake. She did
      not require any further grafting or surgical procedures thereafter. 

PMID- 26199886
TI  - Letter From the Editor.

PMID- 26199887
TI  - Toe Necrosis, Etiologies and Management, a Case Series.
AB  - Toe necrosis may have vast different etiologies. These include ischemia, embolus,
      and others. (1) The most common etiology is ischemia. It is a reduction in blood
      supply to a viable tissue that can lead to susceptibility to infection and tissue
      death. Peripheral ischemia, which is rooted in the lower limbs, is a major risk
      factor for toe necrosis because the basal metabolic requirements of tissue are
      not being sufficiently met. As a result, pain, ulcers, and gangrene commonly
      occur. (2) Other causes of direct and indirect toe necrosis and related lower
      limb gangrene include mechanical trauma, infectious, pharmacological sensitivity,
      cancer, blue toe syndrome, and other granulomatous diseases, such as Churg
      Strauss syndrome. We present a case series of toes necrosis which resulted from
      different etiologies and their management. 

PMID- 26199888
TI  - Prospective, Descriptive Study of Critically Colonized Venous Leg Ulcers Managed
      With Silver Containing Absorbent Dressings and Compression.
AB  - Chronic non-healing venous ulcers are by their very nature colonized with
      bacteria. The amount and make up will vary based on many variables. The
      transition from colonization to contamination, critical colonization, and
      infection complicates the treatment of these ulcers. Silver has been shown to be
      an effective antimicrobial agent with a diverse antimicrobial footprint, minimal
      allergic reactions, and has been employed for over twenty-five years with little
      resistance being encountered. Based on these factors, this study was initiated to
      evaluate the impact of silver containing absorbent dressings on critically
      colonized venous leg ulcers. 

PMID- 26199889
TI  - Use of Topical Small Molecule Technology to Improve Patient Outcomes in the
      Diabetic Wound Care Setting.
AB  - Patients were chosen at random by primary investigator based upon initial
      presentation with dry, cracked, and/or reddened skin, with underlying
      complications from compromised microvasculature. Intervention was conducted by
      using topical products designed to utilize small molecule technologies, with a
      molecular weight of fewer than 500 Da, to deliver, via topical diffusion,
      nutrients and antioxidants through the skin layers to address issues stemming
      from inadequate blood flow to the dermis. An "all-in-one" moisturizing cleansing
      lotion was applied to the affected areas and washed gently with a warm damp
      cloth. After cleansing, the skin was treated with a moisturizing skin cream or a
      chlorhexidine-containing skin shield on areas with redness or advanced breakdown.
      All products contain dimethicone as an active ingredient and are classified as
      OTC skin protectants per approved FDA monographs. Patients were evaluated by the
      primary investigator for noticeable resolution or improvements in dryness,
      scaling, skin cracks, and erythema. 

PMID- 26199890
TI  - GATA Negative Pressure Wound Therapy System.
AB  - The use of negative pressure wound therapy (NPWT) systems has been shown to
      promote wound healing. NPWT systems promise a fast and efficient way of preparing
      wounds for closure by either secondary intention or delayed primary closure, as
      well as for skin grafting and flap covering. While many of its benefits are
      established, commercial NPWT systems are not readily available and may be
      extremely costly for the patient. In the current report, we describe an
      equivalent alternative of NPWT at a substantially lower cost. 

PMID- 26199892
TI  - Letter From the Editor.

PMID- 26199891
TI  - Topical Oxygen for Chronic Wounds: A PRO/CON Debate.
AB  - The role of oxygen in wound healing is universally accepted and does not require
      any further evidence; however the controversy as to whether oxygen delivery
      systems have the potential to improve wound healing remains to be concluded.
      Topical oxygen treatment (TOT) involves the delivery of 100% oxygen for a mean of
      90 min, once a day at an atmospheric pressure slightly above 1 atm abs. The use
      of TOT gained increasing interest recently. The current manuscript will summarize
      the pros and cons of TOT in the view of the available literature. 

PMID- 26199893
TI  - Wound Measurement Techniques: Comparing the Use of Ruler Method, 2D Imaging and
      3D Scanner.
AB  - The statistics on the growing number of non-healing wounds is alarming. In the
      United States, chronic wounds affect 6.5 million patients. An estimated US $25
      billion is spent annually on treatment of chronic wounds and the burden is
      rapidly growing due to increasing health care costs, an aging population and a
      sharp rise in the incidence of diabetes and obesity worldwide.(1) Accurate wound
      measurement techniques will help health care personnel to monitor the wounds
      which will indirectly help improving care.(7,9) The clinical practice of
      measuring wounds has not improved even today.(2,3) A common method like the ruler
      method to measure wounds has poor interrater and intrarater reliability.(2,3)
      Measuring the greatest length by the greatest width perpendicular to the greatest
      length, the perpendicular method, is more valid and reliable than other ruler
      based methods.(2) Another common method like acetate tracing is more accurate
      than the ruler method but still has its disadvantages. These common measurement
      techniques are time consuming with variable inaccuracies. In this study,
      volumetric measurements taken with a non-contact 3-D scanner are benchmarked
      against the common ruler method, acetate grid tracing, and 2-D image planimetry
      volumetric measurement technique. A liquid volumetric fill method is used as the
      control volume. Results support the hypothesis that the 3-D scanner consistently
      shows accurate volumetric measurements in comparison to standard volumetric
      measurements obtained by the waterfill technique (average difference of 11%). The
      3-D scanner measurement technique was found more reliable and valid compared to
      other three techniques, the ruler method (average difference of 75%), acetate
      grid tracing (average difference of 41%), and 2D planimetric measurements
      (average difference of 52%). Acetate tracing showed more accurate measurements
      compared to the ruler method (average difference of 41% (acetate tracing)
      compared to 75% (ruler method)). Improving the accuracy in measuring chronic
      wounds might improve overall care of patients with non-healing wounds. This study
      consistently shows that the 3-D scanner is a more accurate, quicker, and safer
      method for measuring wounds. 

PMID- 26199894
TI  - Sequential Use of Hyperbaric Oxygen, Synthetic Skin Substitute and Skin Grafting
      in the Treatment of a Refractory Vasculitic Ulcer.
AB  - Cutaneous leukocytoclastic vasculitis (CLCV) is a disorder characterized by the
      inflammation of the small vessels of the skin. CLCV may cause recurrent, drug
      resistant, non-healing ulcers. Herein, we present a patient with a recalcitrant
      ulcer caused by CLCV, who was successfully treated with hyperbaric oxygen therapy
      and skin grafting. There is not any particular therapy/product that will heal all
      type of wounds. We can achieve better results provided that wound care products
      and advanced treatments are used at the right time. 

PMID- 26199895
TI  - Lovenox Induced Tissue Necrosis, a Case Report and Literature Review.
AB  - Lovenox is a trade name for Enoxaparin. It is a low molecular weight heparin
      (LMWH) and has other trade names like Clexane and Xaparin. It is an anticoagulant
      used to prevent and treat venous thromboembolism events (VTE) like deep vein
      thrombosis or pulmonary embolism, and is given as a subcutaneous injection.
      General speaking, the most common skin reactions as a result of enoxaparin use
      are: urticarial, ecchymosis, and even skin necrosis due to vasculitis. These side
      effects are usually located at the injection site. New studies have pointed out
      the side effect that could occur a distance from the site of Lovenox injection.
      In our case extensive skin and subcutaneous tissue necrosis developed at the
      abdominal wall injection site. 

PMID- 26199896
TI  - Association of SOCS1 (- 820) (rs33977706) gene polymorphism with chronic
      periodontitis: A case-control study in Brazilians.
AB  - It is evident that the accumulation of periodontal pathogens over the teeth
      surface triggers periodontitis; however, its aggravation and severity depend on
      other elements such as environmental factors, systemic health and the host
      genetic and/or epigenetic background. To address this issue, we investigated the
      association of two genetic polymorphisms placed on promoter region of SOCS1 gene
      with chronic periodontal disease. SOCS1 regulates Jak/Kinase signaling pathway
      and changes in its mRNA expression have been related to different types of cancer
      and chronic inflammation, including chronic periodontitis. The frequency of
      alleles and genotypes of two polymorphisms in SOCS1 gene promoter (position - 820
      (rs33977706) and position - 1478 (rs33989964)) were analyzed by performing RFLP
      and TaqMan system in a total of 257 non-smoking subjects. We found a low
      frequency of A allele and A/A genotype of SOCS1(- 820) polymorphism in the
      chronic periodontitis group, especially when severe periodontitis samples were
      separately analyzed (OR = 0.3933; p = 0.0084 (IC95% 0.2112 < MU < 0.7324)),
      suggesting that A allele plays protective effect against chronic periodontitis.
      We did not find association between SOCS1-1478 polymorphism and periodontitis. In
      addition, analysis of SOCS1 (- 820/- 1478) haplotype revealed that the frequency
      of A(- 820)/CA(- 1478) haplotype decreases in ChrP (p = 0.0089). In conclusion,
      our study found that SOCS1(- 820) polymorphism is associated with chronic
      periodontitis. 

PMID- 26199897
TI  - The Essentiality of Reporting Hardy-Weinberg Equilibrium Calculations in
      Population-Based Genetic Association Studies.
AB  - Population-based genetic association studies have proven to be a powerful tool in
      identifying genes implicated in many complex human diseases that have a huge
      impact on public health. An essential quality control step in such studies is to
      undertake Hardy-Weinberg equilibrium (HWE) calculations. Deviations from HWE in
      the control group may reflect important problems including selection bias,
      population stratification and genotyping errors. If HWE is violated, the
      inferences of these studies may thus be biased. We therefore aimed to examine the
      extent to which HWE calculations are reported in genetic association studies
      published in Cell Journal(Yakhteh)(Cell J). Using keywords pertaining to genetic
      association studies, eleven relevant articles were identified of which ten
      provided full genotypic data. The genotype distribution of 16 single nucleotide
      polymorphisms (SNPs) was re-analyzed for HWE by using three different methods
      where appropriate. HWE was not reported in 60% of all articles investigated.
      Among those reporting, only one article provided calculations correctly and in
      detail. Therefore, 90% of articles analyzed failed to provide sufficient HWE
      data. Interestingly, three articles had significant HWE deviation in their
      control groups of which one highly deviated from HWE expectations (P= 9.8*10(
      12)). We thus show that HWE calculations are under-reported in genetic
      association studies published in this journal. Furthermore, the conclusions of
      the three studies showing significant HWE in their control groups should be
      treated cautiously as they may be potentially misleading. We therefore recommend
      that reporting of detailed HWE calculations should become mandatory for such
      studies in the future. 

PMID- 26199898
TI  - Molecular Aspects of Bone Resorption in beta-Thalassemia Major.
AB  - beta-thalassemia is the most common single gene disorder worldwide, in which
      hemoglobin beta-chain production is decreased. Today, the life expectancy of
      thalassemic patients is increased because of a variety of treatment methods;
      however treatment related complications have also increased. The most common side
      effect is osteoporosis, which usually occurs in early adulthood as a consequence
      of increased bone resorption. Increased bone resorption mainly results from
      factors such as delayed puberty, diabetes mellitus, hypothyroidism, ineffective
      hematopoiesis as well as hyperplasia of the bone marrow, parathyroid gland
      dysfunction, toxic effect of iron on osteoblasts, growth hormone (GH) and insulin
      like growth factor-1 (IGF-1) deficiency. These factors disrupt the balance
      between osteoblasts and osteoclasts by interfering with various molecular
      mechanisms and result in decreased bone density. Given the high prevalence of
      osteopenia and osteoporosis in thalassemic patients and complexity of their
      development process, the goal of this review is to evaluate the molecular aspects
      involved in osteopenia and osteoporosis in thalassemic patients, which may be
      useful for therapeutic purposes. 

PMID- 26199899
TI  - The Important Role of FLT3-L in Ex Vivo Expansion of Hematopoietic Stem Cells
      following Co-Culture with Mesenchymal Stem Cells.
AB  - OBJECTIVE: Hematopoietic stem cells (HSCs) transplantation using umbilical cord
      blood (UCB) has improved during the last decade. Because of cell limitations,
      several studies focused on the ex vivo expansion of HSCs. Numerous investigations
      were performed to introduce the best cytokine cocktails for HSC expansion The
      majority used the Fms-related tyrosine kinase 3 ligand (FLT3-L) as a critical
      component. According to FLT3-L biology, in this study we have investigated the
      hypothesis that FLT3-L only effectively induces HSCs expansion in the presence of
      a mesenchymal stem cell (MSC) feeder. MATERIALS AND METHODS: In this experimental
      study, HSCs and MSCs were isolated from UCB and placenta, respectively. HSCs were
      cultured in different culture conditions in the presence and absence of MSC
      feeder and cytokines. After ten days of culture, total nucleated cell count
      (TNC), cluster of differentiation 34+(CD34(+)) cell count, colony forming unit
      assay (CFU), long-term culture initiating cell (LTC-IC), homeobox protein B4
      (HoxB4) mRNA and surface CD49d expression were evaluated. The fold increase for
      some culture conditions was compared by the t test. RESULTS: HSCs expanded in the
      presence of cytokines and MSCs feeder. The rate of expansion in the co-culture
      condition was two-fold more than culture with cytokines (P<0.05). FLT3-L could
      expand HSCs in the co-culture condition at a level of 20-fold equal to the
      presence of stem cell factor (SCF), thrombopoietin (TPO) and FLT3-L without
      feeder cells. The number of extracted colonies from LTC-IC and CD49d expression
      compared with a cytokine cocktail condition meaningfully increased (P<0.05).
      CONCLUSION: FLT3-L co-culture with MSCs can induce high yield expansion of HSCs
      and be a substitute for the universal cocktail of SCF, TPO and FLT3-L in feeder
      free culture.

PMID- 26199900
TI  - In Vitro Differentiation of Human Umbilical Cord Blood CD133(+)Cells into Insulin
      Producing Cells in Co-Culture with Rat Pancreatic Mesenchymal Stem Cells.
AB  - OBJECTIVE: Pancreatic stroma plays an important role in the induction of
      pancreatic cells by the use of close range signaling. In this respect, we presume
      that pancreatic mesenchymal cells (PMCs) as a fundamental factor of the stromal
      niche may have an effective role in differentiation of umbilical cord blood
      cluster of differentiation 133(+) (UCB-CD133(+)) cells into newly-formed beta
      cells in vitro. MATERIALS AND METHODS: This study is an experimental research.
      The UCB-CD133(+)cells were purified by magnetic activated cell sorting (MACS) and
      differentiated into insulin producing cells (IPCs) in co-culture, both directly
      and indirectly with rat PMCs. Immunocytochemistry and enzyme linked immune
      sorbent assay (ELISA) were used to determine expression and production of insulin
      and C-peptide at the protein level. RESULTS: Our results demonstrated that UCB
      CD133(+)differentiated into IPCs. Cells in islet-like clusters with (out) co
      cultured with rat pancreatic stromal cells produced insulin and C-peptide and
      released them into the culture medium at the end of the induction protocol.
      However they did not respond well to glucose challenges. CONCLUSION: Rat PMCs
      possibly affect differentiation of UCB-CD133(+)cells into IPCs by increasing the
      number of immature beta-cells.

PMID- 26199901
TI  - Effect of Superparamagnetic Iron Oxide Nanoparticles-Labeling on Mouse Embryonic
      Stem Cells.
AB  - OBJECTIVE: Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to
      label mammalian cells and to monitor their fate in vivo using magnetic resonance
      imaging (MRI). However, the effectiveness of phenotype of labeled cells by SPIONs
      is still a matter of question. The aim of this study was to investigate the
      efficiency and biological effects of labeled mouse embryonic stem cells (mESCs)
      using ferumoxide- protamine sulfate complex. MATERIALS AND METHODS: In an
      experimental study, undifferentiated mESCs, C571 line, a generous gift of Stem
      Cell Technology Company, were cultured on gelatin-coated flasks. The
      proliferation and viability of SPION-labeled cells were compared with control.
      ESCs and embryoid bodies (EBs) derived from differentiated hematopoietic stem
      cells (HSCs) were analyzed for stage-specific cell surface markers using
      fluorescence-activated cell sorting (FACS). RESULTS: Our observations showed that
      SPIONs have no effect on the self-renewal ability of mESCs. Reverse microscopic
      observations and prussian blue staining revealed 100% of cells were labeled with
      iron particles. SPION-labeled mESCs did not significantly alter cell viability
      and proliferation activity. Furthermore, labeling did not alter expression of
      representative surface phenotypic markers such as stage-specific embryonic
      antigen 1 (SSEA1) and cluster of differentiation 117 (CD117) on undifferentiated
      ESC and CD34, CD38 on HSCs, as measured by flowcytometry. CONCLUSION: According
      to the results of the present study, SPIONs-labeling method as MRI agents in
      mESCs has no negative effects on growth, morphology, viability, proliferation and
      differentiation that can be monitored in vivo, noninvasively. Noninvasive cell
      tracking methods are considered as new perspectives in cell therapy for clinical
      use and as an easy method for evaluating the placement of stem cells after
      transplantation.

PMID- 26199902
TI  - Differentiation of Human Mesenchymal Stem Cells into Insulin Producing Cells by
      Using A Lentiviral Vector Carrying PDX1.
AB  - OBJECTIVE: Type I diabetes is an immunologically-mediated devastation of insulin
      producing cells (IPCs) in the pancreatic islet. Stem cells that produce beta
      cells are a new promising tool. Adult stem cells such as mesenchymal stem cells
      (MSCs) are self renewing multi potent cells showing capabilities to differentiate
      into ectodermal, mesodermal and endodermal tissues. Pancreatic and duodenal
      homeobox factor 1 (PDX1) is a master regulator gene required for embryonic
      development of the pancreas and is crucial for normal pancreatic islets
      activities in adults. MATERIALS AND METHODS: We induced the over-expression of
      the PDX1 gene in human bone marrow MSCs (BM-MSCs) by Lenti-PDX1 in order to
      generate IPCs. Next, we examine the ability of the cells by measuring insulin/c
      peptide production and INSULIN and PDX1 gene expressions. RESULTS: After
      transduction, MSCs changed their morphology at day 5 and gradually differentiated
      into IPCs. INSULIN and PDX1 expressions were confirmed by real time polymerase
      chain reaction (RT-PCR) and immunostaining. IPC secreted insulin and C-peptide in
      the media that contained different glucose concentrations. CONCLUSION: MSCs
      differentiated into IPCs by genetic manipulation. Our result showed that
      lentiviral vectors could deliver PDX1 gene to MSCs and induce pancreatic
      differentiation.

PMID- 26199903
TI  - Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet
      Rich Plasma Accelerate Distraction Osteogenesis in A Canine Model.
AB  - OBJECTIVE: Distraction osteogenesis (DO) is a surgical procedure used to generate
      large volumes of new bone for limb lengthening. MATERIALS AND METHODS: In this
      animal experimental study, a 30% lengthening of the left tibia (mean distraction
      distance: 60.8 mm) was performed in ten adult male dogs by callus distraction
      after osteotomy and application of an Ilizarov fixator. Distraction was started
      on postoperative day seven with a distraction rate of 0.5 mm twice per day and
      carried out at a rate of 1.5 mm per day until the end of the study. Autologous
      bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich plasma (PRP) as
      the treatment group (n=5) or PRP alone (control group, n=5) were injected into
      the distracted callus at the middle and end of the distraction period. At the end
      of the consolidation period, the dogs were sacrificed after which computerized
      tomography (CT) and histomorphometric evaluations were performed. RESULTS:
      Radiographic evaluationsrevealed that the amount and quality of callus formations
      were significantly higher in the treatment group (P<0.05). As measured by CT
      scan, the healing parametersin dogs of the treatment group were significantly
      greater (P<0.05). New bone formation in the treatment group was significantly
      higher (P<0.05). CONCLUSION: The present study showed that the transplantation of
      BM-MSCs positively affects early bony consolidation in DO. The use of MSCs might
      allow a shortened period of consolidation and therefore permit earlier device
      removal.

PMID- 26199904
TI  - Effects of Perivitelline Fluid Obtained from Horseshoe Crab on The Proliferation
      and Genotoxicity of Dental Pulp Stem Cells.
AB  - OBJECTIVE: Perivitelline fluid (PVF) of the horseshoe crab embryo has been
      reported to possess an important role during embryogenesis by promoting cell
      proliferation. This study aims to evaluate the effect of PVF on the
      proliferation, chromosome aberration (CA) and mutagenicity of the dental pulp
      stem cells (DPSCs). MATERIALS AND METHODS: This is an in vitro experimental
      study. PVF samples were collected from horseshoe crabs from beaches in Malaysia
      and the crude extract was prepared. DPSCs were treated with different
      concentrations of PVF crude extract in an 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) assay (cytotoxicity test). We choose two
      inhibitory concentrations (IC50 and IC25) and two PVF concentrations which
      produced more cell viability compared to a negative control (100%) for further
      tests. Quantitative analysis of the proliferation activity of PVF was studied
      using the AlamarBlue(r)assay for 10 days. Population doubling times (PDTs) of the
      treatment groups were calculated from this assay. Genotoxicity was evaluated
      based on the CA and Ames tests. Statistical analysis was carried out using
      independent t test to calculate significant differences in the PDT and mitotic
      indices in the CA test between the treatment and negative control groups.
      Significant differences in the data were P<0.05. RESULTS: A total of four PVF
      concentrations retrieved from the MTT assay were 26.887 mg/ml (IC50), 14.093
      mg/ml (IC25), 0.278 mg/ml (102% cell viability) and 0.019 mg/ml (102.5% cell
      viability). According to the AlamarBlue(r)assay, these PVF groups produced
      comparable proliferation activities compared to the negative (untreated) control.
      PDTs between PVF groups and the negative control were insignificantly different
      (P>0.05). No significant aberrations in chromosomes were observed in the PVF
      groups and the Ames test on the PVF showed the absence of significant positive
      results. CONCLUSION: PVF from horseshoe crabs produced insignificant
      proliferative activity on treated DPSCs. The PVF was non-genotoxic based on the
      CA and Ames tests.

PMID- 26199905
TI  - Optimization of Buffalo (Bubalus bubalis) Embryonic Stem Cell Culture System.
AB  - OBJECTIVE: In order to retain an undifferentiated pluripotent state, embryonic
      stem (ES) cells have to be cultured on feeder cell layers. However, use of feeder
      layers limits stem cell research, since experimental data may result from a
      combined ES cell and feeder cell response to various stimuli. MATERIALS AND
      METHODS: In this experimental study, a buffalo ES cell line was established from
      in vitro derived blastocysts and characterized by the Alkaline phosphatase (AP)
      and immunoflourescence staining of various pluripotency markers. We examined the
      effect of various factors like fibroblast growth factor 2 (FGF-2), leukemia
      inhibitory factor (LIF) and Y-27632 to support the growth and maintenance of
      bubaline ES cells on gelatin coated dishes, in order to establish feeder free
      culture systems. We also analyzed the effect of feeder-conditioned media on stem
      cell growth in gelatin based cultures both in the presence as well as in the
      absence of the growth factors. RESULTS: The results showed that Y-27632, in the
      presence of FGF-2 and LIF, resulted in higher colony growth and increased
      expression of Nanog gene. Feeder-Conditioned Medium resulted in a significant
      increase in growth of buffalo ES cells on gelatin coated plates, however, feeder
      layer based cultures produced better results than gelatin based cultures. Feeder
      layers from buffalo fetal fibroblast cells can support buffalo ES cells for more
      than two years. CONCLUSION: We developed a feeder free culture system that can
      maintain buffalo ES cells in the short term, as well as feeder layer based
      culture that can support the long term maintenance of buffalo ES cells.

PMID- 26199906
TI  - Downregulation of Vascular Endothelial Growth Factor Enhances Chemosensitivity by
      Induction of Apoptosis in Hepatocellular Carcinoma Cells.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC), one of the most common cancers
      worldwide, is resistant to anticancer drugs. Angiogenesis is a major cause of
      tumor resistance to chemotherapy, and vascular endothelial growth factor (VEGF)
      is a key regulator of angiogenesis. The purpose of this study is to investigate
      the impact of small-interfering RNA targeting VEGF gene (VEGF-siRNA) on
      chemosensitivity of HCC cells in vitro. MATERIALS AND METHODS: In this
      experimental study, transfection was performed on Hep3B cells. After transfection
      with siRNAs, VEGF mRNA and protein levels were examined. Cell proliferation,
      apoptosis and anti-apoptotic gene expression were also analyzed after treatment
      with VEGF-siRNA in combination with doxorubicin in Hep3B cells. RESULTS:
      Transfection of VEGF-siRNA into Hep3B cells significantly reduced the expression
      of VEGF at both mRNA and protein levels. Combination therapy with VEGF-siRNA and
      doxorubicin more effectively suppressed cell proliferation and induced apoptosis
      than the respective monotherapies. This could be explained by the significant
      downregulation of B-cell lymphoma 2 (BCL-2) and SURVIVIN. CONCLUSION: VEGF-siRNA
      enhanced the chemosensitivity of doxorubicin in Hep3B cells at least in part by
      suppressing the expression of anti-apoptotic genes. Therefore, the downregulation
      of VEGF by siRNA combined with doxorubicin treatment has been shown to yield
      promising results for eradicating HCC cells.

PMID- 26199907
TI  - Generation of Rat Embryonic Germ Cells via Inhibition of TGFbeta and MEK
      Pathways.
AB  - OBJECTIVE: Embryonic germ (EG) cells are the results of reprogramming primordial
      germ cells (PGC) in vitro. Studying these cells can be of benefit in determining
      the mechanism by which specialized cells acquire pluripotency. Therefore in the
      current study we have tried to derive rat EG cells with inhibition of
      transforming growth factor-beta (TGFbeta) and mitogen-activated protein kinase
      kinase (MEK) signaling pathways. MATERIALS AND METHODS: In this experimental
      study, rat PGCs were cultured under feeder free condition with two small
      molecules that inhibited the above mentioned pathways. Under this condition only
      two-day presence of stem cell factor (SCF) as a survival factor was applied for
      PGC reprogramming. Pluripotency of the resultant EG cells were further confirmed
      by immunofluorescent staining, directed differentiation ability to neural and
      cardiac cells, and their contribution to teratoma formation as well. Moreover,
      chromosomal stability of two different EG cells were assessed through G-banding
      technique. RESULTS: Formerly, derivation of rat EG cells were observed solely in
      the presence of glycogen synthase kinase-3 (GSK3beta) and MEK pathway inhibitors.
      Due to some drawbacks of inhibiting GSK3beta molecules such as increases in
      chromosomal aberrations, in the present study we have attempted to assess a
      feeder-free protocol that derives EG cells by the simultaneous suppression of
      TGFbeta signaling and the MEK pathway. We have shown that rat EG cells could be
      generated in the presence of two inhibitors that suppressed the above mentioned
      pathways. Of note, inhibition of TGFbeta instead of GSK3beta significantly
      maintained chromosomal integrity. The resultant EG cells demonstrated the
      hallmarks of pluripotency in protein expression level and also showed in vivo and
      in vitro differentiation capacities. CONCLUSION: Rat EG cells with higher
      karyotype stability establish from PGCs by inhibiting TGFbeta and MEK signaling
      pathways.

PMID- 26199908
TI  - The Effect of Nano-Titanium Dioxide on Limb Bud Development of NMRI Mouse Embryo
      In Vivo.
AB  - OBJECTIVE: There is a wide application of titanium dioxide (TiO2) nanoparticles
      (NPs) in industry. These particles are used in various products, and they also
      has biological effects on cells and organs through direct contact. MATERIALS AND
      METHODS: In this experimental research, the effect of TiO2 on chondrogenesis of
      forelimb buds of mice embryos was assessed in in vivo condition. Concentrations
      of 30, 150 and 500 mg/kg body weight (BW) TiO2 NPs (20 nm size) dissolved in
      distilled water were injected intraperitoneally to Naval Medical Research
      Institute (NMRI) mice on day 11.5 of gestation. On day 15, limb buds were
      amputated from the embryos and skeletogeneis of limb buds were studied. RESULTS:
      TiO2 NPs caused the significant changes in chondrocytes in the following
      developmental stages: resting, proliferating, hypertrophy, degenerating,
      perichondrium and mesenchymal cells. Decreased number of mesenchymal cells and
      increased level of chondrocytes were observed after the injection of different
      concentrations of TiO2, which proves the unpredictable effects of TiO2 on limb
      buds. CONCLUSION: Results of the present study showed TiO2 NPs accelerated the
      chondrogenesis of limb buds, but further studies are recommended to predict TiO2
      toxicity effects on organogenesis.

PMID- 26199909
TI  - Time-Dependent Effect of Encapsulating Alginate Hydrogel on Neurogenic Potential.
AB  - OBJECTIVE: Due to the restricted potential of neural stem cells for regeneration
      of central nervous system (CNS) after injury, providing an alternative source for
      neural stem cells is essential. Adipose derived stem cells (ADSCs) are
      multipotent cells with properties suitable for tissue engineering. In addition,
      alginate hydrogel is a biocompatible polysaccharide polymer that has been used to
      encapsulate many types of cells. The aim of this study was to assess the
      proliferation rate and level of expression of neural markers; NESTIN, glial
      fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) in
      encapsulated human ADSCs (hADSCs) 10 and14 days after neural induction. MATERIALS
      AND METHODS: In this experimental study, ADSCs isolated from human were cultured
      in neural induction media and seeded into alginate hydrogel. The rate of
      proliferation and differentiation of encapsulated cells were evaluated by 3-[4, 5
      dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay,
      immunocytoflourescent and realtime reverse transcriptase polymerase chain
      reaction (RT-PCR) analyzes 10 and 14 days after induction. RESULTS: The rate of
      proliferation of encapsulated cells was not significantly changed with time
      passage. The expression of NESTIN and GFAP significantly decreased on day 14
      relative to day 10 (P<0.001) but MAP2 expression was increased. CONCLUSION:
      Alginate hydrogel can promote the neural differentiation of encapsulated hADSCs
      with time passage.

PMID- 26199910
TI  - Genotoxic Damage to Glioblastoma Cells Treated with 6 MV X-Radiation in The
      Presence or Absence of Methoxy Estradiol, IUDR or Topotecan.
AB  - OBJECTIVE: To explore the cumulative genotoxic damage to glioblastoma (GBM)
      cells, grown as multicellular spheroids, following exposure to 6 MV X-rays (2 Gy,
      22 Gy) with or without, 2- methoxy estradiol (2ME2), iododeoxyuridine (IUDR) or
      topotecan (TPT), using the Picogreen assay. MATERIALS AND METHODS: The U87MG
      cells cultured as spheroids were treated with 6 MV X-ray using linear
      accelerator. Specimens were divided into five groups and irradiated using X-ray
      giving the dose of 2 Gy after sequentially incubated with one of the following
      three drug combinations: TPT, 2-ME2/TPT, IUDR/TPT or 2ME2/IUDR/ TPT. One specimen
      was used as the irradiated only sample (R). The last group was also irradiated
      with total dose of 22 Gy (each time 2 Gy) of 6 MV X-ray in 11 fractions and
      treated for three times. DNA damage was evaluated using the Picogreen method in
      the experimental study. RESULTS: R/TPT treated group had more DNA damage [double
      strand break (DSB)/single strand break (SSB)] compared with the untreated group
      (P<0.05). Moreover the R/ TPT group treated with 2ME2 followed by IUDR had
      maximum DNA damage in spheroid GBM indicating an augmented genotoxicity in the
      cells. The DNA damage was induced after seven fractionated irradiation and two
      sequential treatments with 2ME2/IUDR/TPT. To ensure accuracy of the slope of dose
      response curve the fractionated radiation was calculated as 7.36 Gy with respect
      to alpha/beta ratio based on biologically effective dose (BED) formulae.
      CONCLUSION: Cells treated with 2ME2/IUDR showed more sensitivity to radiation and
      accumulative DNA damage. DNA damage was significantly increased when GBM cells
      treated with TPT ceased at S phase due to the inhibition of topoisomerase enzyme
      and phosphorylation of Chk1 enzyme. These results suggest that R/TPT- treated
      cells increase sensitivity to 2ME2 and IUDR especially when they are used
      together. Therefore, due to an increase in the level of DNA damage (SSB vs. DSB)
      and impairment of DNA repair machinery, more cell death will occur. This in turn
      may improve the treatment of GBM.

PMID- 26199911
TI  - Effects of Wi-Fi (2.45 GHz) Exposure on Apoptosis, Sperm Parameters and
      Testicular Histomorphometry in Rats: A Time Course Study.
AB  - OBJECTIVE: In today's world, 2.45-GHz radio-frequency radiation (RFR) from
      industrial, scientific, medical, military and domestic applications is the main
      part of indoor-outdoor electromagnetic field exposure. Long-term effects of 2.45
      GHz Wi-Fi radiation on male reproductive system was not known completely.
      Therefore, this study aimed to investigate the major cause of male infertility
      during short- and long-term exposure of Wi-Fi radiation. MATERIALS AND METHODS:
      This is an animal experimental study, which was conducted in the Department of
      Anatomical Sciences, Faculty of Medicine, Zanjan University of Medical Sciences,
      Zanjan, IRAN, from June to August 2014. Three-month-old male Wistar rats (n=27)
      were exposed to the 2.45 GHz radiation in a chamber with two Wi-Fi antennas on
      opposite walls. Animals were divided into the three following groups: I. control
      group (n=9) including healthy animals without any exposure to the antenna, II. 1
      hour group (n=9) exposed to the 2.45 GHz Wi-Fi radiation for 1 hour per day
      during two months and III.7-hour group (n=9) exposed to the 2.45 GHz Wi-Fi
      radiation for 7 hours per day during 2 months. Sperm parameters, caspase-3
      concentrations, histomorphometric changes of testis in addition to the apoptotic
      indexes were evaluated in the exposed and control animals. RESULTS: Both 1-hour
      and 7-hour groups showed a decrease in sperm parameters in a time dependent
      pattern. In parallel, the number of apoptosis-positive cells and caspase-3
      activity increased in the seminiferous tubules of exposed rats. The seminal
      vesicle weight reduced significantly in both1-hour or 7-hour groups in comparison
      to the control group. CONCLUSION: Regarding to the progressive privilege of 2.45
      GHz wireless networks in our environment, we concluded that there should be a
      major concern regarding the timedependent exposure of whole-body to the higher
      frequencies of Wi-Fi networks existing in the vicinity of our living places.

PMID- 26199912
TI  - Maternal-Effect Gene Expression in Cultured Preantral Follicles Derived from
      Vitrified-Warmed Mouse Ovary.
AB  - OBJECTIVE: This study was conducted to assess survival of follicles, their oocyte
      maturation and fertilization potential as well as expression of early embryo
      developmental genes in in vitro cultured pre-antral follicles derived from
      vitrified-warmed mouse ovary. MATERIALS AND METHODS: In this experimental study,
      ovaries of 12-day old Naval Medical Research Institute (NMRI) female mice were
      placed into non-vitrified and vitrifiedwarmed groups. Isolated preantral
      follicles from experimental groups were cultured in vitro for 12 days. On the
      12(th) day of culture, oocyte maturation was induced and then matured oocytes
      were in vitro fertilized. The rates of oocyte maturation and two-cell stage
      embryo formation were assessed. Relative expression of Mater and Zar1 was
      evaluated on days 1, 6, 10 and 12 of culture. Data analysis was performed by t
      test and two-way ANOVA (P<0.05). RESULTS: Our data showed no significant
      difference between the control and vitrification groups in the rate of follicular
      survival, oocyte maturation and two-cell stage embryo formation. The level of
      gene expression was higher on the 6(th)and 10(th)days of culture for Mater and
      Zar1 in vitrified-warmed group compared with non-vitrified group, however, there
      was no significant difference between the two groups. CONCLUSION: It seems that
      the applied vitrification method did not reveal any negative effect on maturation
      and developmental competence of oocytes surrounded in preantral follicles and
      therefore could preserve follicular reserves efficiently.

PMID- 26199913
TI  - Transcription Profiles of Marker Genes Predict The Transdifferentiation
      Relationship between Eight Types of Liver Cell during Rat Liver Regeneration.
AB  - OBJECTIVE: To investigate the transdifferentiation relationship between eight
      types of liver cell during rat liver regeneration (LR). MATERIALS AND METHODS:
      114 healthy Sprague-Dawley (SD) rats were used in this experimental study. Eight
      types of liver cell were isolated and purified with percoll density gradient
      centrifugation and immunomagentic bead methods. Marker genes for eight types of
      cell were obtained by retrieving the relevant references and databases.
      Expression changes of markers for each cell of the eight cell types were measured
      using microarray. The relationships between the expression profiles of marker
      genes and transdifferentiation among liver cells were analyzed using
      bioinformatics. Liver cell transdifferentiation was predicted by comparing
      expression profiles of marker genes in different liver cells. RESULTS: During LR
      hepatocytes (HCs) not only express hepatic oval cells (HOC) markers (including
      PROM1, KRT14 and LY6E), but also express biliary epithelial cell (BEC) markers
      (including KRT7 and KRT19); BECs express both HOC markers (including GABRP, PCNA
      and THY1) and HC markers such as CPS1, TAT, KRT8 and KRT18; both HC markers
      (KRT18, KRT8 and WT1) and BEC markers (KRT7 and KRT19) were detected in HOCs.
      Additionally, some HC markers were also significantly upregulated in hepatic
      stellate cells ( HSCs), sinusoidal endothelial cells (SECs) , Kupffer cells (KCs)
      and dendritic cells (DCs), mainly at 6-72 hours post partial hepatectomy (PH).
      CONCLUSION: Our findings indicate that there is a mutual transdifferentiation
      relationship between HC, BEC and HOC during LR, and a tendency for HSCs, SECs,
      KCs and DCs to transdifferentiate into HCs.

PMID- 26199914
TI  - N-Acetyl Cysteine Inhibits Endothelin-1-Induced ROS Dependent Cardiac Hypertrophy
      through Superoxide Dismutase Regulation.
AB  - OBJECTIVE: Oxidative stress down regulates antioxidant enzymes including
      superoxide dismutase (SOD) and contributes to the development of cardiac
      hypertrophy. N-Acetyl cysteine (NAC) can enhance the SOD activity, so the aim of
      this study is to highlight the inhibitory role of NAC against endothelin-1 (ET-1)
      induced cardiac hypertrophy. MATERIALS AND METHODS: In this experimental study at
      QAU from January, 2013 to March, 2013. ET-1 (50 ug/kg) and NAC (50 mg/kg) were
      given intraperitoneally to 6-day old neonatal rats in combination or alone. All
      rats were sacrificed 15 days after the final injection. Histological analysis was
      carried out to observe the effects caused by both drugs. Reactive oxygen species
      (ROS) analysis and SOD assay were also carried out. Expression level of hyper-
      trophic marker, brain natriuretic peptide (BNP), was detected by western
      blotting. RESULTS: Our findings showed that ET-1-induced cardiac hypertrophy
      leading towards heart failure was due to the imbalance of different parameters
      including free radical-induced oxidative stress and antioxidative enzymes such as
      SOD. Furthermore NAC acted as an antioxidant and played inhibitory role against
      ROS-dependent hypertrophy via regulatory role of SOD as a result of oxidative
      response associated with hypertrophy. CONCLUSION: ET-1-induced hypertrophic
      response is associated with increased ROS production and decreased SOD level,
      while NAC plays a role against free radicals-induced oxidative stress via SOD
      regulation.

PMID- 26199915
TI  - On The Protection by The Combination of CeO2 Nanoparticles and Sodium Selenite on
      Human Lymphocytes against Chlorpyrifos-Induced Apoptosis In Vitro.
AB  - OBJECTIVE: Chlorpyrifos (CP) as an organophosphorus pesticide is thought to
      induce oxidative stress in human cells via producing reactive oxygen species
      (ROS) that leads to the presence of pathologic conditions due to apoptosis along
      with acetylcholinesterase (AChE) inhibition.This study aimed to evaluate the
      apoptotic effects of CP and to assess the protective potential of
      CeO2nanoparticle (CNP) and sodium selenite (SSe) by measuring cascades of
      apoptosis, oxidative stress, inflammation, and AChE inhibition in human isolated
      lymphocytes. MATERIALS AND METHODS: In the present experimental study, we
      examined the anti-oxidative and AChE activating potential of CNP and SSe in CP
      treated human lymphocytes. Therefore, the lymphocytes were isolated and exposed
      to CP, CP+CNP, CP+SSe, and CP+CNP+SSe after a three-day incubation. Then tumor
      necrosis factor-alpha (TNF-alpha) release, myeloperoxidase (MPO) activity,
      thiobarbituric acid-reactive substances (TBARS) levels as inflammatory/oxidative
      stress indices along with AChE activity were assessed. In addition, the apoptotic
      process was measured by flow cytometry. RESULTS: Results showed a significant
      reduction in the mortality rate, TNF-alpha, MPO activity, TBARS, and apoptosis
      rate in cells treated with CNP, SSe and their combination. Interestingly, both
      CNP and SSe were able to activate AChE which is inhibited by CP. The results
      supported the synergistic effect of CNP/SSe combination in the prevention of
      apoptosis along with oxidative stress and inflammatory cascade. CONCLUSION: CP
      induces apoptosis in isolated human lymphocytes via oxidative stress and
      inflammatory mediators. CP firstly produces ROS, which leads to membrane
      phospholipid damage. The beneficial effects of CNP and SSe in reduction of CP
      induced apoptosis and restoring AChE inhibition relate to their anti-oxidative
      potentials.

PMID- 26199916
TI  - Rapid Scientific Promotion of Scientific Productions in Stem Cells According to
      The Indexed Papers in The ISI (web of knowledge).
AB  - OBJECTIVE: In recent years emphasis has been placed on evaluation studies and the
      publication of scientific papers in national and international journals. In this
      regard the publication of scientific papers in journals in the Institute for
      Scientific Information (ISI) database is highly recommended. The evaluation of
      scientific output via articles in journals indexed in the ISI database will
      enable the Iranian research authorities to allocate and organize research budgets
      and human resources in a way that maximises efficient science production. The
      purpose of the present paper is to publish a general and valid view of science
      production in the field of stem cells. MATERIALS AND METHODS: In this research,
      outputs in the field of stem cell research are evaluated by survey research, the
      method of science assessment called Scientometrics in this branch of science. A
      total of 1528 documents was extracted from the ISI database and analysed using
      descriptive statistics software in Excel. RESULTS: The results of this research
      showed that 1528 papers in the stem cell field in the Web of Knowledge database
      were produced by Iranian researchers. The top ten Iranian researchers in this
      field have produced 936 of these papers, equivalent to 61.3% of the total. Among
      the top ten, Soleimani M. has occupied the first place with 181 papers. Regarding
      international scientific participation, Iranian researchers have cooperated to
      publish papers with researchers from 50 countries. Nearly 32% (452 papers) of the
      total research output in this field has been published in the top 10 journals.
      CONCLUSION: These results show that a small number of researchers have published
      the majority of papers in the stem cell field. International participation in
      this field of research unacceptably low. Such participation provides the
      opportunity to import modern science and international experience into Iran. This
      not only causes scientific growth, but also improves the research and enhances
      opportunities for employment and professional development. Iranian scientific
      outputs from stem cell research should not be limited to only a few specific
      journals.

PMID- 26199917
TI  - Protective Effects of Diallyl Sulfide and Curcumin Separately against Thallium
      Induced Toxicity in Rats.
AB  - Thallium acetate (TI) is a cumulative poison intimately accompanied by an
      increase in reactive oxygen species (ROS) formation that represents an important
      risk factor for tissue injury and malfunction. This study aims to determine the
      possible hepatoprotective and antioxidant effects of diallyl sulfide (DAS) from
      garlic and curcumin from turmeric against TI-induced liver injury and oxidative
      stress (OS) in rats. This in vivo animal study divided rats into six groups of 8
      rats per group. The first group received saline and served as the control group.
      The second and third groups received DAS or curcumin only at a dose of 200 mg/kg.
      The fourth group received TI at a dose of 6.4 mg/kg for 5 consecutive days. The
      fifth and sixth groups received DAS or curcumin orally 1 hour before TI
      intoxication at the same dose as the second and third groups. Liver integrity
      serum enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma
      glutamyltransferase (gamma-GT) were evaluated. Serum and liver tissue homogenate
      lipid peroxidation and OS biomarkers were measured. The data were analyzed by one
      way ANOVA followed by Duncan's multiple range test for post hoc analysis using
      SPSS version 16. TI induced marked oxidative liver damage as shown by
      significantly (P<=0.05) elevated serum AST, ALT, ALP, LDH and gamma-GT levels.
      There were significant (P<=0.05) increases in serum and hepatic malondialdehyde
      (MDA) and serum nitric oxide (NO) as well as decreased hepatic glutathione (GSH)
      and catalase (CAT) activities. There were significantly (P<=0.05) less serum and
      hepatic superoxide dismutase (SOD) and total antioxidant capacity (TAC). Pre
      treatment with DAS or curcumin ameliorated the changes in most studied
      biochemical parameters. DAS and curcumin effectively reduced TI-induced liver
      toxicity. 

PMID- 26199918
TI  - Improved Quality of Life in A Case of Cerebral Palsy after Bone Marrow
      Mononuclear Cell Transplantation.
AB  - Cerebral palsy (CP) is a non progressive, demyelinating disorder that affects a
      child's development and posture and may be associated with sensation, cognition,
      communication and perception abnormalities. In CP, cerebral white matter is
      injured resulting in the loss of oligodendrocytes. This causes damage to the
      myelin and disruption of nerve conduction. Cell therapy is being explored as an
      alternate therapeutic strategy as there is no treatment currently available for
      CP. To study the benefits of this treatment we have administered autologous bone
      marrow mononuclear cells (BMMNCs) to a 12-year-old CP case. He was clinically re
      evaluated after six months and found to demonstrate positive clinical and
      functional outcomes. His trunk strength, upper limb control, hand functions,
      walking stability, balance, posture and coordination improved. His ability to
      perform activities of daily living improved. On repeating the Functional
      Independence Measure (FIM), the score increased from 90 to 113. A repeat positron
      emission tomography-computed tomography (PET-CT) scan of the brain six months
      after intervention showed progression of the mean standard deviation values
      towards normalization which correlated to the functional changes. At one year,
      all clinical improvements have remained. This indicated that cell transplantation
      may improve quality of life and have a potential for treatment of CP. 

PMID- 26199919
TI  - Association between Periodontitis and Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease which significantly
      increases with age. Its onset can be either early or late. AD is characterized by
      the salient inflammatory features, microglial activation, and increased levels of
      proinflammatory cytokines which contribute to the inflammatory status of the
      central nervous system (CNS). Whereas, periodontitis is a common oral infection
      associated with the gram negative anaerobic bacteria. Periodontitis can be marked
      as a "low-grade systemic disease" by release of proinflammatory cytokines into
      systemic circulation and elevation of C-reactive protein (CRP). Inflammation is
      known to play a pivotal role in both the disease process serving as a connecting
      link between periodontitis and AD. The present review throws a light on possible
      enigmatic link between AD and periodontitis. This review is designed by
      collecting data from PubMed database using key words like "Alzheimer's disease",
      "inflammation", "periodontitis", and "proinflammatory cytokines". 

PMID- 26199920
TI  - Abdominal Tuberculosis: An Immigrant's Disease in the United States.
AB  - BACKGROUND: Abdominal tuberculosis (TB) is an uncommon condition in the United
      States (US) except for patients with human immunodeficiency virus (HIV). An
      increasing number of cases have been reported in western countries amongst
      immigrants. It is important to be aware of the data and clinical characteristics
      in the immigrant population. AIMS: The purpose of this study is to determine the
      epidemiologic characteristics of abdominal TB among immigrants in the US and to
      review the clinical presentations of abdominal TB with a focus particularly on
      unusual features. MATERIALS AND METHODS: In a community teaching hospital in New
      Jersey, patients diagnosed with abdominal TB were examined and included in this
      report. All nine patients were immigrants from countries with high prevalence of
      TB and a majority had resided in the US for at least 5 years. None had clinical
      evidence of HIV and those that were tested were not found to be positive for HIV.
      Initial examination, diagnostic workup, and response to therapy were all
      pertinent to the management and diagnosis of these patients. RESULTS: Three
      patients had atypical clinical presentations with normal chest X-rays and either
      negative or unknown tuberculin tests leading to delayed diagnosis and
      inappropriate therapy in at least one patient. With antituberculous therapy, all
      except for one patient had satisfactory outcomes. Immigrant patients with a
      diagnosis of abdominal TB had no evidence of HIV infection or other associated
      conditions in contrast to native-born individuals. CONCLUSION: Atypical
      presentations may cause diagnostic difficulties. Failure to perform appropriate
      tests may lead to inappropriate therapy with adverse outcomes. Although there is
      a decline in the number of TB cases in the US and screening for latent pulmonary
      infection in foreigners has been implemented effectively, the diagnosis of
      abdominal TB continues to be under diagnosed.

PMID- 26199921
TI  - Respiratory Burst Enzymes, Pro-Oxidants and Antioxidants Status in Bangladeshi
      Population with beta-Thalassemia Major.
AB  - BACKGROUND: Oxidative stress is intimately associated with many diseases,
      including beta-thalassemia. AIM: The study was to estimate the status of
      respiratory burst enzymes, pro-oxidants, and antioxidants in beta-thalassemia
      major patients in Bangladesh and to compare with apparently healthy individuals.
      MATERIALS AND METHODS: A total of 49 subjects were recruited which included 25
      patients (age range 5 to 40 years) with beta-thalassemia major and 24 controls
      (age and sex matched). Superoxide dismutase (SOD) and catalase (CAT) represented
      respiratory burst enzymes; malondialdehyde (MDA), lipid hydroperoxide (LHP), and
      xanthine oxidase (XO) were measured as pro-oxidants; and glutathione S
      transferase (GST), vitamin C (Vit.C), and glutathione (GSH) were the measured
      antioxidants. RESULTS: The activity of SOD was significantly (P < 0.001)
      increased by about 79% and the activity of CAT was significantly (P < 0.001)
      decreased by more than 34% in the blood of beta-thalassemia major patients
      compared to the control group. The content of pro-oxidants such as MDA, LHP, and
      XO was significantly (P < 0.001) higher in patients by about 228%, 241.3% and
      148.1% respectively compared to control group. The level of GSH and Vit.C were
      significantly (P = 0.000) decreased in patients by about 59% and 81% versus the
      healthy group, respectively; and GST activity was significantly (P < 0.001)
      declined by 44.25% in patients group. CONCLUSION: beta-thalassemia major patients
      demonstrate raised oxidative stress compared to healthy subjects.

PMID- 26199922
TI  - Predictors of Morbidity and Mortality in Organophosphorus Poisoning: A Case Study
      in Rural Hospital in Karnataka, India.
AB  - BACKGROUND: Organophosphorus (OP) pesticides poisoning can result from
      occupational, accidental or intentional exposure. Clinical manifestations include
      cholinergic syndromes, central nervous (CNS) system and cardiovascular disorders.
      Death is usually due to cardiovascular and respiratory failure. AIM: To evaluate
      various parameters that can predict outcome of patients in OP poisoning.
      MATERIALS AND METHODS: A prospective study conducted in Department of Medicine,
      Adichunchingiri Institute Of medical Sciences and Research Centre, Karnataka,
      over period of 1 year. Diagnosis of OP poisoning was based on clinical history of
      exposure to OP compound and low serum pseudocholinesterase levels. RESULTS: In
      the present study 133 patients were enrolled, out of which 98.5% were suicidal
      cases and only 1.5% had accidental exposure. Majority of cases were young male,
      with F/M ratio 1:3.2. Mortality rates were higher in younger people and in
      patients who required prolonged ventilator support. The mortality rate was
      directly proportional to amount of poison consumed, lag time, organ failure
      (Acute Renal Failure) and plasma pseudocholinesterase levels. Acute complications
      were frequently noted and were related to morbidity and mortality. No strict
      relationship was found between liver dysfunction, electrolyte disturbance and
      clinical outcome. CONCLUSION: This case study concluded that mortality is
      directly proportionate to the lag time, amount of OP substances consumed,
      clinical severity, pseudocholinesterase levels, Acute renal failure and duration
      of ventilatory support. This study highlights the importance of rapid diagnosis,
      and initiation of early and effective treatment, which may result in less number
      complications and also decreases the mortality rates.

PMID- 26199923
TI  - Effectiveness of Group Versus Individual Yoga Exercises on Fatigue of Patients
      with Multiple Sclerosis.
AB  - BACKGROUND: Multiple sclerosis disorders poses heavy physical and emotional
      effect on patients who are associated with the disease. AIM: This study aimed to
      compare the effectiveness of individual versus group exercises on fatigue on
      patients with multiple sclerosis. MATERIALS AND METHODS: In this clinical trial,
      85 patients with multiple sclerosis were divided in two groups of individualized
      exercise and team exercise. The intervention was conducted for 6 weeks and
      comprised of mild stretching and basic yoga exercises twice a day. The data were
      collected through demographic questionnaire, standard fatigue scale and self
      reported checklist. Data analysis was performed by SPSS software. RESULTS: The
      mean levels of fatigue perception after the intervention in group exercise was
      27.9 +/- 15.9 and 27.1 +/- 17.2 in individual exercise. There was no significant
      difference between the two groups (P > 0.05). Statistically significant
      difference was observed in the mean level of perceived fatigue in triplicate
      measurements (P = 0.013) among patients who completed individual exercise.
      However, this difference was not significant in the group exercise. CONCLUSION:
      Performing mild stretching exercises and basic yoga are recommended as a cost
      effective method which is easy to perform among patients with mild to moderate
      disabilities.

PMID- 26199924
TI  - Inverse Correlation between Serum C-Reactive Protein and Magnesium Levels in
      Smokers and Nonsmokers.
AB  - BACKGROUND: Smoking plays a key role in increasing the inflammatory marker C
      reactive protein (CRP). AIMS: To examine inverse correlation between CRP and
      magnesium levels in smokers and nonsmokers. MATERIALS AND METHODS: A total of 192
      healthy adult male subjects were included in the present study, out of which 96
      were smokers and the remaining 96 were nonsmokers having age range from 20 to 40
      years, and all the subjects belonged to District Matyari of Hyderabad. Serum CRP
      was measured by NycoCard standard kit method and magnesium levels by DiaSys
      standard kit method in smokers and nonsmokers. RESULTS: The levels of serum CRP
      in smokers (14.62 +/- 0.16 mg/L) is high as compared to nonsmokers (4.81 +/- 0.38
      mg/L), which is highly significant (P < 0.001). However, inverse results were
      seen for serum magnesium levels which were significantly higher (P < 0.001) in
      nonsmokers (2.52 +/- 0.18 mg/L) as compared to the smokers (1.09 +/- 0.38 mg/dL).
      A significant (P < 0.001) inverse relationship between serum CRP and magnesium
      concentrations were seen in smokers. CONCLUSION: This result shows that smoking
      increases serum CRP, an inflammatory marker parallel to decrease in serum
      magnesium levels in smokers having 20-40 years of age.

PMID- 26199925
TI  - Markers for Sebaceoma Show a Spectrum of Cell Cycle Regulators, Tumor Suppressor
      Genes, and Oncogenes.
AB  - BACKGROUND: Sebaceoma is a tumor for which the causative oncogenes are not well
      understood. Sebaceomas demonstrate some histopathologic features similar to basal
      cell carcinoma (BCC), such as palisading borders and basaloid cells with
      additional features, including foamy cytoplasm and indented nuclei. AIMS: We
      examine multiple cell-cycle, oncogene, and tumor suppressor gene markers in
      sebaceomas, to try to find some suitable biological markers for this tumor, and
      compare with other published studies. MATERIALS AND METHODS: We investigated a
      panel of immunohistochemical (IHC) stains that are important for cellular
      signaling, including a cell cycle regulator, tumor suppressor gene, oncogene,
      hormone receptor, and genomic stability markers in our cohort of sebaceomas. We
      collected 30 sebaceomas from three separate USA dermatopathology laboratories.
      The following IHC panel: Epithelial membrane antigen (EMA)/CD227, cytokeratin
      AE1/AE3, cyclin D1, human breast cancer 1 protein (BRCA-1), C-erb-2, Bcl-2, human
      androgen receptor (AR), cyclin-dependent kinase inhibitor 1B (p27(kip1)), p53,
      topoisomerase II alpha, proliferating cell nuclear antigen, and Ki-67 were tested
      in our cases. RESULTS: EMA/CD227 was positive in the well-differentiated
      sebaceomas (13/30). Cyclin-dependent kinase inhibitor 1B was positive in tumors
      with intermediate differentiation (22/30). The less well-differentiated tumors
      failed to stain with EMA and AR. Most of the tumors with well-differentiated
      palisaded areas demonstrated positive staining for topoisomerase II alpha,
      p27(kip1), and p53, with positive staining in tumoral basaloid areas (22/30).
      Numerous tumors were focally positive with multiple markers, indicating a
      significant degree of variability in the complete group. CONCLUSIONS: Oncogenes,
      tumor suppressor genes, cell cycle regulators, and hormone receptors are variably
      expressed in sebaceomas. Our results suggest that in these tumors, selected
      marker staining seems to correlate with tumor differentiation; that is, well
      differentiated tumors as a group stained with EMA and AR, and palisaded areas
      demonstrated consistent p53, topoisomerase II alpha and p27(kip1) staining. In
      contrast, less well-differentiated areas stained with a different spectrum of
      markers.

PMID- 26199926
TI  - Impact of Carotid Intima-Media Thickness on Long-term Outcome in Hemodialysis
      Patients.
AB  - BACKGROUND: Chronic kidney disease (CKD) patients on hemodialysis are highly
      prone to cardiovascular disease, which accounts for roughly half of the mortality
      in these patients. Atherosclerosis begins many years before the development of
      clinical manifestations. Measurement of carotid intima-media thickness (CIMT) is
      a noninvasive procedure to detect early atherosclerotic changes. AIMS: The aim of
      the study was to evaluate the correlation between CIMT and cardiovascular risk
      factors and to investigate its prognostic significance in CKD patients on
      hemodialysis. MATERIALS AND METHODS: This was a prospective study carried out
      over a period of 18 months. Total 88 patients on hemodialysis and 50 healthy
      controls were enrolled in the study. Biochemical assay and CIMT was assessed
      using the high resolution 7.5 MHz sonography technique in all subjects. RESULTS:
      Significant positive correlation was found with age, blood urea, serum
      creatinine, serum triglyceride, low-density lipoprotein, serum phosphorus, serum
      calcium-phosphorus product, serum uric acid, 24 h urine protein, systolic blood
      pressure, diastolic blood pressure, and body mass index. Negative correlation was
      found with estimated glomerular filtration rate. Adjusted hazards ratios of all
      cause and cardiovascular mortality for an increase of 0.1 mm in CIMT was 1.16
      (95% confidence interval 0.15-9.09). Patients with CIMT value <0.97 mm had a
      renal survival rate of 73.4% while patients with value >0.97 mm had a renal
      survival rate of 16.5%. CONCLUSION: Uremia is an additive risk factors in those
      subjects who have raised CIMT despite of traditional cardiovascular risk factors.

PMID- 26199928
TI  - Euglycemic Diabetic Ketoacidosis, a Misleading Presentation of Diabetic
      Ketoacidosis.
AB  - CONTEXT: Diabetic ketoacidosis (DKA) is one of the most serious complications of
      diabetes. It is characterized by a triad of increased total body ketone
      concentration, metabolic acidosis, and uncontrolled hyperglycemia. Hyperglycemia
      is a key diagnostic criterion of DKA; however, in some rare cases, normal glucose
      levels can be present. CASE REPORTS: We describe two patients with type 1
      diabetes mellitus (DM1); one who presented with a Bartholin's gland abscess and
      the other with acute pancreatitis. Both patients had maintained adequate
      hydration and continued to take their insulin without sufficient carbohydrate
      intake in the previous days prior to presentation. Despite their normal serum
      glucose levels upon presentation, they were found to have ketonemia and acidosis
      consistent with DKA. If only the serum glucose level was taken into
      consideration, while ignoring the rest of their biochemical profiles and failing
      to obtain ketone levels, the diagnoses would have been missed. CONCLUSION:
      Euglycemic DKA is usually seen in otherwise healthy patients with type 1 diabetes
      mellitus who have decreased carbohydrate intake in the presence of adequate
      hydration and a degree of insulin intake. Recognition of this entity by the
      emergency provider is crucial when patients with DM1 present with a picture of
      DKA, regardless of their blood sugar.

PMID- 26199927
TI  - Hairy Cell Leukemia Presenting with Duodenal Involvement Duodenum: A Case Report.
AB  - CONTEXT: A rare case of adult hairy cell leukemia (HCL) with duodenal involvement
      is presented. CASE REPORT: The patient was a 48-year-old man, who had a history
      of hairy cell leukemia. Three days after completion of 2-chlorodeoxyadenosine
      (CDA) chemotherapy, the patient started experiencing abdominal pain. An extensive
      gastroenterological workup culminated in the patient getting an
      esophagogastroduodenoscopy (EGD) that revealed duodenal inflammation and biopsies
      were taken. The duodenal biopsy was positive for chronic inflammatory infiltrate,
      primarily consisting of atypical lymphocytes and plasma cells with tartrate
      resistant acid phosphatase (TRAP) positivity, and hence a diagnosis of duodenal
      involvement with HCL was made. Repeat bone marrow biopsy done 2 weeks after
      finishing chemotherapy revealed residual disease. At the 3-month follow-up, the
      patient was asymptomatic with a normocellular marrow and no residual disease.
      Repeat abdomen computerized tomography (CT) scan at completion of therapy showed
      resolution of duodenal thickening and spleen size of 12 cm. Currently, patient is
      in clinical remission for 6 years with 4-6 monthly follow-up visits and continues
      to do well. CONCLUSION: This case is presented to highlight the first case report
      of HCL with duodenal involvement that was successfully treated with CDA.

PMID- 26199929
TI  - Recalcitrant Digital Porokeratosis of Mibelli: A Successful Surgical Treatment.
AB  - CONTEXT: Porokeratosis of Mibelli (PM) is a rare, benign, asymptomatic, epidermal
      hyperkeratinization dermatitis that is characterized by annular plaque that
      expands through the edges and leaves an atrophic center. Many therapies have been
      attempted for the treatment of PM, but none of these have given satisfactory
      results. The efficacies of treatment options are limited, and currently there is
      no gold standard. CASE REPORT: This paper reports the case of a 22-year-old
      female with 3-years history of PM, who had not responded to routine therapies
      like topical corticosteroids, topical tretinoin, topical salicylic acid, and
      various emollients and keratolytic agent. Cryosurgery and laser ablation did not
      have acceptable response. We used surgical treatment with successful cosmetic
      outcome. CONCLUSION: The treatment of PM should be individualized considering the
      aesthetic and functionality, and the patient's preferences. Complete surgical
      excision for isolated digital PM had good results.

PMID- 26199930
TI  - Ebola Paranoia in the Age of the Internet and Social Media.

PMID- 26199931
TI  - Psychiatric Patients Experiences with Mechanical Restraints: An Interview Study.
AB  - Objective. To examine psychiatric patients' experience of mechanical restraints
      and to describe the care the patients received. Background. All around the world,
      threats and violence perpetrated by patients in psychiatric emergency inpatient
      units are quite common and are a prevalent factor concerning the application of
      mechanical restraints, although psychiatric patients' experiences of mechanical
      restraints are still moderately unknown. Method. A qualitative design with an
      inductive approach were used, based on interviews with patients who once been in
      restraints. Results. This study resulted in an overbridging theme: Physical
      Presence, Instruction and Composed Behaviour Can Reduce Discontent and Trauma,
      including five categories. These findings implicated the following: information
      must be given in a calm and sensitive way, staff must be physically present
      during the whole procedure, and debriefing after the incident must be conducted.
      Conclusions. When mechanical restraints were unavoidable, the presence of
      committed staff during mechanical restraint was important, demonstrating the
      significance of training acute psychiatric nurses correctly so that their
      presence is meaningful. Nurses in acute psychiatric settings should be required
      to be genuinely committed, aware of their actions, and fully present in coercive
      situations where patients are vulnerable. 

PMID- 26199932
TI  - Polymorphisms of Leptin (-2548 G/A) and Leptin Receptor (Q223R) Genes in Iranian
      Women with Breast Cancer.
AB  - Recent studies have shown that polymorphisms in leptin and leptin receptor genes
      are associated with increased risk for breast cancer. This study aimed at
      investigating -2548 G/A polymorphism in leptin gene and Q223R polymorphism in
      leptin receptor gene in patients with breast cancer. The study included 45 women
      with breast cancer and 41 healthy women. PCR-RFLP was used to determine the
      genotype of the subjects in terms of -2548 G/A polymorphism in leptin gene and
      Q223R polymorphism in leptin receptor gene. Serum levels of leptin were also
      measured by ELISA. For -2548 G/A polymorphism, the genotypes were homozygous AA
      (OR = 1.13; p = 0.8) and heterozygous GA (OR = 0.41; p = 0.2) and for Q223R
      polymorphism, the genotypes were homozygous RR (OR = 6.7; p = 0.09) and
      heterozygous QR (OR = 8.3; p = 0.06). The mean serum level of leptin was 33.22 +/
      21.35 ng/mL in patients and 29.49 +/- 23.27 ng/mL in the normal participants (p
      = 0.3). Although, despite the magnitude of the associations, the results
      suggested no statistically significant contribution of -2548 G/A polymorphism (in
      leptin gene), Q223R polymorphism (in leptin receptor gene), and serum leptin
      levels in predicting the risk of breast cancer, further studies with larger
      sample size are suggested. 

PMID- 26199933
TI  - The Glycine max cv. Enrei Genome for Improvement of Japanese Soybean Cultivars.
AB  - We elucidated the genome sequence of Glycine max cv. Enrei to provide a reference
      for characterization of Japanese domestic soybean cultivars. The whole genome
      sequence obtained using a next-generation sequencer was used for reference
      mapping into the current genome assembly of G. max cv. Williams 82 obtained by
      the Soybean Genome Sequencing Consortium in the USA. After sequencing and
      assembling the whole genome shotgun reads, we obtained a data set with about 928
      Mbs total bases and 60,838 gene models. Phylogenetic analysis provided glimpses
      into the ancestral relationships of both cultivars and their divergence from the
      complex that include the wild relatives of soybean. The gene models were analyzed
      in relation to traits associated with anthocyanin and flavonoid biosynthesis and
      an overall profile of the proteome. The sequence data are made available in
      DAIZUbase in order to provide a comprehensive informatics resource for
      comparative genomics of a wide range of soybean cultivars in Japan and a
      reference tool for improvement of soybean cultivars worldwide. 

PMID- 26199934
TI  - Relationship between Metabolic Syndrome and Lower Urinary Tract Symptoms: Hallym
      Aging Study.
AB  - The aim of the study was to test the hypothesis that the metabolic syndrome (MS)
      is linked to lower urinary tract symptoms (LUTS) in Korean men. This was a
      longitudinal study that used data collected from 328 men aged 50-89 years who
      were randomly selected among 1,520 participants in 2004. We collected information
      from 224 (68.3%) men among the original responders on the biological, medical,
      psychological, social, lifestyle, and economic factors in 2007. The prevalence of
      the MS was 187/328 (57.0%) in 2004 and 125/224 (55.8%) in 2007 among men,
      respectively. There was no significantly greater increase in the IPSS in men with
      the MS than in men without the MS over a 3-year period of time (2.0 +/- 9.37
      versus 3.0 +/- 8.44, p = 0.402, resp.). In the multivariate logistic regression
      analysis with control for age and life style factors, the risk factors for
      moderate/severe LUTS were age and erectile dysfunction (p < 0.05). However, the
      presence of the MS did not increase the risk of moderate/severe LUTS (OR = 1.09,
      95% CI 0.63-1.89, p = 0.748). Our cross-sectional and longitudinal risk factor
      analyses do not support the hypothesis that the MS is linked to LUTS in Korean
      men. 

PMID- 26199935
TI  - New Technologies for the Management and Rehabilitation of Chronic Diseases and
      Conditions.

PMID- 26199936
TI  - Genotoxicity of Anesthetics Evaluated In Vivo (Animals).
AB  - The anesthesia has been improved all over the years. However, it can have impact
      on health, in both patients and animals anesthetized, as well as professionals
      exposed to inhaled anesthetics. There is continuing effort to understand the
      possible effects of anesthetics at molecular levels. Knowing the effects of
      anesthetic agents on genetic material could be a valuable basic support to better
      understand the possible mechanisms of these agents. Thus, the purpose of this
      review is to provide an overview on the genotoxic potential, evaluated in animal
      models, of many anesthetics that have already been used and those currently used
      in anesthesia. 

PMID- 26199937
TI  - Gold Nanoparticles Promote Oxidant-Mediated Activation of NF-kappaB and 53BP1
      Recruitment-Based Adaptive Response in Human Astrocytes.
AB  - Nanogold-based materials are promising candidate tools for nanobased medicine.
      Nevertheless, no conclusive information on their cytotoxicity is available. In
      the present study, we investigated the effects of gold nanoparticles (AuNPs) on
      human astrocytes in vitro. Nanogold treatment in a wide range of concentrations
      did not result in cytotoxicity. In contrast, nanogold provoked changes in the
      astrocyte cell cycle and induced senescence-associated beta-galactosidase
      activity. AuNPs promoted oxidative stress and caused activation of NF-kappaB
      pathway. After nanogold treatment, an inverse correlation between the formation
      of 53BP1 foci and micronuclei generation was observed. The robust 53BP1
      recruitment resulted in reduced micronuclei production. Thus, nanogold treatment
      stimulated an adaptive response in a human astrocyte cell. 

PMID- 26199938
TI  - Chemical, Bioactive, and Antioxidant Potential of Twenty Wild Culinary Mushroom
      Species.
AB  - The chemical, bioactive, and antioxidant potential of twenty wild culinary
      mushroom species being consumed by the people of northern Himalayan regions has
      been evaluated for the first time in the present study. Nutrients analyzed
      include protein, crude fat, fibres, carbohydrates, and monosaccharides. Besides,
      preliminary study on the detection of toxic compounds was done on these species.
      Bioactive compounds evaluated are fatty acids, amino acids, tocopherol content,
      carotenoids (beta-carotene, lycopene), flavonoids, ascorbic acid, and
      anthocyanidins. Fruitbodies extract of all the species was tested for different
      types of antioxidant assays. Although differences were observed in the net values
      of individual species all the species were found to be rich in protein, and
      carbohydrates and low in fat. Glucose was found to be the major monosaccharide.
      Predominance of UFA (65-70%) over SFA (30-35%) was observed in all the species
      with considerable amounts of other bioactive compounds. All the species showed
      higher effectiveness for antioxidant capacities. 

PMID- 26199939
TI  - Cancer Immunology and Immunotherapy.

PMID- 26199941
TI  - Advances in Airway Management and Ventilation Strategies in Emergency Medicine.

PMID- 26199942
TI  - The Thermal Sensitivity Test in Evaluating Outcome after Peripheral Nerve Injury.
AB  - The purpose of this study was to evaluate the ability to discriminate
      temperatures in patients following peripheral nerve injury. Knowing that
      temperature sensibility is mediated by different receptors, the scores were
      compared to other functional hand scores in order to determine whether the
      ability to discriminate temperatures is restored to a different extent compared
      with other commonly evaluated hand function modalities. The test was performed
      using the NTE-2 device (Physitemp Instruments Inc., 154 Huron Avenue, Clifton,
      New Jersey, USA). Out of 57 patients, 27 had normal thermal discrimination
      scores, and 9 could not tell the temperatures apart in the differences set on the
      measuring device. Overall, patients with better thermal discrimination had also
      better hand function as evaluated with different methods. However, some patients
      who did regain the ability to differentiate temperatures correctly did not have
      any measurable return of hand function in other tests. Thermal discrimination
      scores correlated similarly with different functional scores, except for
      vibration sensibility, which did not show any significant correlation. The
      development and severity of cold intolerance seem to be unrelated to temperature
      sense. 

PMID- 26199943
TI  - Targeted Next-Generation Sequencing Reveals Hot Spots and Doubly Heterozygous
      Mutations in Chinese Patients with Familial Cardiomyopathy.
AB  - As a common cardiac disease mainly caused by gene mutations in sarcomeric
      cytoskeletal, calcium-handling, nuclear envelope, desmosomal, and transcription
      factor genes, inherited cardiomyopathy is becoming one of the major etiological
      factors of sudden cardiac death (SCD) and heart failure (HF). This disease is
      characterized by remarkable genetic heterogeneity, which makes it difficult to
      screen for pathogenic mutations using Sanger sequencing. In the present study,
      three probands, one with familial hypertrophic cardiomyopathy (FHCM) and two with
      familial dilated cardiomyopathy (FDCM), were recruited together with their
      respective family members. Using next-generation sequencing technology (NGS), 24
      genes frequently known to be related to inherited cardiomyopathy were screened.
      Two hot spots (TNNI3-p.Arg145Gly, and LMNA-p.Arg190Trp) and double (LMNA
      p.Arg190Trp plus MYH7-p.Arg1045His) heterozygous mutations were found to be
      highly correlated with familial cardiomyopathy. FDCM patients with doubly
      heterozygous mutations show a notably severe phenotype as we could confirm in our
      study; this indicates that the double mutations had a dose effect. In addition,
      it is proposed that genetic testing using NGS technology can be used as a cost
      effective screening tool and help guide the treatment of patients with familial
      cardiomyopathy particularly regarding the risk of family members who are
      clinically asymptomatic. 

PMID- 26199940
TI  - Single-Stranded DNA Aptamers against Pathogens and Toxins: Identification and
      Biosensing Applications.
AB  - Molecular recognition elements (MREs) can be short sequences of single-stranded
      DNA, RNA, small peptides, or antibody fragments. They can bind to user-defined
      targets with high affinity and specificity. There has been an increasing interest
      in the identification and application of nucleic acid molecular recognition
      elements, commonly known as aptamers, since they were first described in 1990 by
      the Gold and Szostak laboratories. A large number of target specific nucleic
      acids MREs and their applications are currently in the literature. This review
      first describes the general methodologies used in identifying single-stranded DNA
      (ssDNA) aptamers. It then summarizes advancements in the identification and
      biosensing application of ssDNA aptamers specific for bacteria, viruses, their
      associated molecules, and selected chemical toxins. Lastly, an overview of the
      basic principles of ssDNA aptamer-based biosensors is discussed. 

PMID- 26199944
TI  - Novel FGFR1 and KISS1R Mutations in Chinese Kallmann Syndrome Males with Cleft
      Lip/Palate.
AB  - Kallmann syndrome (KS) is characterized by isolated hypogonadotropic hypogonadism
      (IHH) with anosmia and is sometimes associated with cleft lip/palate (CLP). In
      order to describe the clinical features, genetic etiology, and treatment outcome
      of KS males with CLP, we performed genetic screening for 15 known causal IHH
      genes (KAL1, FGFR1, NELF, FGF8, CHD7, WDR11, SEMA3A, KISS1R, KISS1, PROKR2,
      PROK2, TAC3, TACR3, GNRH1, and GNRHR) in four KS with CLP patients and six IHH
      patients without CLP. Two novel heterozygous missense mutations in FGFR1,
      (NM_001174066): c.776G>A (p.G259E) and (NM_001174066): c.358C>T (p.R120C), were
      identified in a 23-year-old KS male with cleft lip and an 18-year-old KS patient
      with cleft lip and palate, dental agenesis, and high arched palate, respectively.
      These two mutations were not presented in their healthy parents and 200 normal
      controls. One novel heterozygous missense mutation in KISS1R, (NM_032551):
      c.587C>A (p.P196H), was identified in an 18-year-old KS male with cleft lip and
      dental agenesis who developed sperm after being treated with gonadotropin. This
      mutation was also presented in his healthy father and grandfather. These results
      have implications for the diagnosis, genetic counseling, and treatment of KS and
      CLP males with mutations in FGFR1 gene. 

PMID- 26199945
TI  - Cyanobacteria: Photoautotrophic Microbial Factories for the Sustainable Synthesis
      of Industrial Products.
AB  - Cyanobacteria are widely distributed Gram-negative bacteria with a long
      evolutionary history and the only prokaryotes that perform plant-like oxygenic
      photosynthesis. Cyanobacteria possess several advantages as hosts for
      biotechnological applications, including simple growth requirements, ease of
      genetic manipulation, and attractive platforms for carbon neutral production
      process. The use of photosynthetic cyanobacteria to directly convert carbon
      dioxide to biofuels is an emerging area of interest. Equipped with the ability to
      degrade environmental pollutants and remove heavy metals, cyanobacteria are
      promising tools for bioremediation and wastewater treatment. Cyanobacteria are
      characterized by the ability to produce a spectrum of bioactive compounds with
      antibacterial, antifungal, antiviral, and antialgal properties that are of
      pharmaceutical and agricultural significance. Several strains of cyanobacteria
      are also sources of high-value chemicals, for example, pigments, vitamins, and
      enzymes. Recent advances in biotechnological approaches have facilitated
      researches directed towards maximizing the production of desired products in
      cyanobacteria and realizing the potential of these bacteria for various
      industrial applications. In this review, the potential of cyanobacteria as
      sources of energy, bioactive compounds, high-value chemicals, and tools for
      aquatic bioremediation and recent progress in engineering cyanobacteria for these
      bioindustrial applications are discussed. 

PMID- 26199946
TI  - GESearch: An Interactive GUI Tool for Identifying Gene Expression Signature.
AB  - The huge amount of gene expression data generated by microarray and next
      generation sequencing technologies present challenges to exploit their biological
      meanings. When searching for the coexpression genes, the data mining process is
      largely affected by selection of algorithms. Thus, it is highly desirable to
      provide multiple options of algorithms in the user-friendly analytical toolkit to
      explore the gene expression signatures. For this purpose, we developed GESearch,
      an interactive graphical user interface (GUI) toolkit, which is written in MATLAB
      and supports a variety of gene expression data files. This analytical toolkit
      provides four models, including the mean, the regression, the delegate, and the
      ensemble models, to identify the coexpression genes, and enables the users to
      filter data and to select gene expression patterns by browsing the display window
      or by importing knowledge-based genes. Subsequently, the utility of this
      analytical toolkit is demonstrated by analyzing two sets of real-life microarray
      datasets from cell-cycle experiments. Overall, we have developed an interactive
      GUI toolkit that allows for choosing multiple algorithms for analyzing the gene
      expression signatures. 

PMID- 26199947
TI  - The Protective Effect of Radix Polygoni Multiflori on Diabetic Encephalopathy via
      Regulating Myosin Light Chain Kinase Expression.
AB  - Currently there has been no effective treatment of diabetic encephalopathy. Radix
      Polygoni Multiflori, a famous traditional Chinese medicine, is widely used in
      antiaging treatment, especially in prevention and treatment of Alzheimer's
      diseases. In this study we tried to explore the effect of Radix Polygoni
      Multiflori on cognitive function among diabetic rats with demonstrated cognitive
      impairment. SD rats were divided into group A (control group), group B
      (diabetes), group C (treated with Radix Polygoni Multiflori at the dose of 2
      g/kg/d), and group D (treated with same drug at the dose of 1 g/kg/d). The
      results showed that 8 weeks of Radix Polygoni Multiflori treatment could improve
      the cognitive dysfunction of diabetic rats (P < 0.01), recover the ultrastructure
      of hippocampal neurons, and increase the number of synapses in a dose-dependent
      manner. Further experiment also suggested that the neuroprotective effect of
      Radix Polygoni Multiflori was partly achieved by downregulating MLCK expression
      in hippocampus via ERK signaling.

PMID- 26199948
TI  - The Complex Role of STAT3 in Viral Infections.
AB  - Signal transducer and activators of transcription-3 (STAT3) regulates diverse
      biological functions including cell growth, differentiation, and apoptosis. In
      addition, STAT3 plays a key role in regulating host immune and inflammatory
      responses and in the pathogenesis of many cancers. Several studies reported
      differential regulation of STAT3 in a range of viral infections. Interestingly,
      STAT3 appears to direct seemingly contradictory responses and both pro- and
      antiviral roles of STAT3 have been described. This review summarized the
      currently known functions of STAT3 in the regulation of viral replication and
      pathogenesis of viral infections. Some of the key unanswered questions and the
      gap in our current understanding of the role of STAT3 in viral pathogenesis are
      discussed. 

PMID- 26199950
TI  - Host Characteristics and Bacterial Traits Predict Experimental Virulence for
      Escherichia coli Bloodstream Isolates From Patients With Urosepsis.
AB  - Background.  Extraintestinal Escherichia coli infections are common, costly, and
      potentially serious. A better understanding of their pathogenesis is needed.
      Methods.  Sixty-seven E coli bloodstream isolates from adults with urosepsis
      (Seattle, WA; 1980s) underwent extensive molecular characterization and virulence
      assessment in 2 infection models (murine subcutaneous sepsis and moth larval
      lethality). Statistical comparisons were made among host characteristics,
      bacterial traits, and experimental virulence. Results.  The 67 source patients
      were diverse for age, sex, and underlying medical and urological conditions. The
      corresponding E coli isolates exhibited diverse phylogenetic backgrounds and
      virulence profiles. Despite the E coli isolates' common bloodstream origin, they
      exhibited a broad range of experimental virulence in mice and moth larvae, in
      patterns that (for the murine model only) corresponded significantly with host
      characteristics and bacterial traits. The most highly mouse-lethal strains were
      enriched with classic "urovirulence" traits and typically were from younger women
      with anatomically and functionally normal urinary tracts. The 2 animal models
      corresponded poorly with one another. Conclusions.  Host compromise, including
      older age and urinary tract abnormalities, allows comparatively low-virulence E
      coli strains to cause urosepsis. Multiple E coli traits predict both experimental
      and epidemiological virulence. The larval lethality model cannot be a substitute
      for the murine sepsis model. 

PMID- 26199949
TI  - First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant
      Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090).
AB  - Background.  We report the first-in-human safety and immunogenicity evaluation of
      a highly attenuated, replication-competent recombinant vesicular stomatitis virus
      (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods.  Sixty healthy, HIV
      1-uninfected adults were enrolled in a randomized, double-blinded, placebo
      controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1
      gag vaccine at 5 dose levels (4.6 * 10(3) to 3.4 * 10(7) particle forming units)
      (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral
      injections at 0 and 2 months. Safety monitoring included VSV cultures from blood,
      urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing
      antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were
      assessed. Results.  Local and systemic reactogenicity symptoms were mild to
      moderate and increased with dose. No severe reactogenicity or product-related
      serious adverse events were reported, and all rVSV cultures were negative. All
      vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific
      T-cell responses were detected in 63% of participants by interferon-gamma enzyme
      linked immunospot at the highest dose post boost. Conclusions.  An attenuated
      replication-competent rVSV gag vaccine has an acceptable safety profile in
      healthy adults. This rVSV vector is a promising new vaccine platform for the
      development of vaccines to combat HIV-1 and other serious human diseases. 

PMID- 26199951
TI  - AAV-mediated RLBP1 gene therapy improves the rate of dark adaptation in Rlbp1
      knockout mice.
AB  - Recessive mutations in RLBP1 cause a form of retinitis pigmentosa in which the
      retina, before its degeneration leads to blindness, abnormally slowly recovers
      sensitivity after exposure to light. To develop a potential gene therapy for this
      condition, we tested multiple recombinant adeno-associated vectors (rAAVs)
      composed of different promoters, capsid serotypes, and genome conformations. We
      generated rAAVs in which sequences from the promoters of the human RLBP1, RPE65,
      or BEST1 genes drove the expression of a reporter gene (green fluorescent
      protein). A promoter derived from the RLBP1 gene mediated expression in the
      retinal pigment epithelium and Muller cells (the intended target cell types) at
      qualitatively higher levels than in other retinal cell types in wild-type mice
      and monkeys. With this promoter upstream of the coding sequence of the human
      RLBP1 gene, we compared the potencies of vectors with an AAV2 versus an AAV8
      capsid in transducing mouse retinas, and we compared vectors with a self
      complementary versus a single-stranded genome. The optimal vector (scAAV8-pRLBP1
      hRLBP1) had serotype 8 capsid and a self-complementary genome. Subretinal
      injection of scAAV8-pRLBP1-hRLBP1 in Rlbp1 nullizygous mice improved the rate of
      dark adaptation based on scotopic (rod-plus-cone) and photopic (cone)
      electroretinograms (ERGs). The effect was still present after 1 year. 

PMID- 26199952
TI  - Disease modeling and lentiviral gene transfer in patient-specific induced
      pluripotent stem cells from late-onset Pompe disease patient.
AB  - Pompe disease is an autosomal recessive inherited metabolic disease caused by
      deficiency of acid alpha-glucosidase (GAA). Glycogen accumulation is seen in the
      affected organ such as skeletal muscle, heart, and liver. Hypertrophic
      cardiomyopathy is frequently seen in the infantile onset Pompe disease. On the
      other hand, cardiovascular complication of the late-onset Pompe disease is
      considered as less frequent and severe than that of infantile onset. There are
      few investigations which show cardiovascular complication of late onset Pompe
      disease due to the shortage of appropriate disease model. We have generated late
      onset Pompe disease-specific induced pluripotent stem cell (iPSC) and
      differentiated them into cardiomyocytes. Differentiated cardiomyocyte shows
      glycogen accumulation and lysosomal enlargement. Lentiviral GAA rescue improves
      GAA enzyme activity and glycogen accumulation in iPSC. The efficacy of gene
      therapy is maintained following the cardiomyocyte differentiation. Lentiviral GAA
      transfer ameliorates the disease-specific change in cardiomyocyote. It is
      suggested that Pompe disease iPSC-derived cardiomyocyte is replicating disease
      specific changes in the context of disease modeling, drug screening, and cell
      therapy. 

PMID- 26199953
TI  - Fuzzy Number Addition with the Application of Horizontal Membership Functions.
AB  - The paper presents addition of fuzzy numbers realised with the application of the
      multidimensional RDM arithmetic and horizontal membership functions (MFs). Fuzzy
      arithmetic (FA) is a very difficult task because operations should be performed
      here on multidimensional information granules. Instead, a lot of FA methods use
      alpha-cuts in connection with 1-dimensional classical interval arithmetic that
      operates not on multidimensional granules but on 1-dimensional intervals. Such
      approach causes difficulties in calculations and is a reason for arithmetical
      paradoxes. The multidimensional approach allows for removing drawbacks and
      weaknesses of FA. It is possible thanks to the application of horizontal
      membership functions which considerably facilitate calculations because now
      uncertain values can be inserted directly into equations without using the
      extension principle. The paper shows how the addition operation can be realised
      on independent fuzzy numbers and on partly or fully dependent fuzzy numbers with
      taking into account the order relation and how to solve equations, which can be a
      difficult task for 1-dimensional FAs. 

PMID- 26199954
TI  - Mathematical Problems for Complex Systems.

PMID- 26199956
TI  - Response.

PMID- 26199955
TI  - Hyaluronic Acid (800 kDa) Supplementation of University of Wisconsin Solution
      Improves Viability of Osteochondral Grafts and Reduces Matrix Metalloproteinase
      Expression during Cold Preservation.
AB  - Osteochondral allografting is a promising option for the treatment of large
      cartilage defects. However, because the cell viability of osteochondral tissues
      (OCTs) gradually reduces during storage at 4 degrees C, methods for maintaining
      the cell viability of fresh OCTs are needed to improve transplantation outcomes.
      Here, we evaluated whether the supplementation of preservation solution with one
      of three different molecular weight forms of hyaluronic acid (HA) improved the
      viability of rat OCTs during long-term cold storage. The supplementation of
      University of Wisconsin (UW) solution with 800 kDa significantly improved the
      cell viability of OCT after 14 days at 4 degrees C compared to nonsupplemented UW
      solution. In contrast, UW solution supplemented with either 1900 or 6000 kDa HA
      did not markedly improve the cell viability of the OCT. Real-time PCR analysis
      revealed that the levels of matrix metalloproteinases 2, 3, and 9 were
      significantly decreased in OCT stored in UW solution supplemented with 800 kDa
      HA. Although further studies in human OCT are warranted, these findings
      demonstrate that the use of 800 kDa HA in place of serum may be a suitable
      approach for the long-term preservation of osteochondral allografts designated
      for the repair of large cartilage defects in the clinical setting.

PMID- 26199957
TI  - Response.

PMID- 26199958
TI  - Response.

PMID- 26199959
TI  - Response.

PMID- 26199960
TI  - [AAD 2915 - area of conflict between medicine and politics].

PMID- 26199961
TI  - [Employment of unlicensed assistants has expensive consequences].

PMID- 26199962
TI  - [Visualization and emotions - how to give a good presentation].

PMID- 26199964
TI  - [Comment on "Cardiovascular disease in Europe 2014: epidemiological update"].
AB  - This paper provides an update for 2014 on the burden of cardiovascular disease
      (CVD), and in particular coronary heart disease (CHD) and stroke, across the
      countries of Europe. Cardiovascular disease causes more deaths among Europeans
      than any other condition, and in many countries still causes more than twice as
      many deaths as cancer. There is clear evidence in most countries with available
      data that mortality and case-fatality rates from CHD and stroke have decreased
      substantially over the last 5-10 years but at differing rates. The differing
      recent trends have therefore led to increasing inequalities in the burden of CVD
      between countries. For some Eastern European countries, including Russia and
      Ukraine, the mortality rate for CHD for 55-60 year olds is greater than the
      equivalent rate in France for people 20 years older.

PMID- 26199963
TI  - Additional Sleep Duration Associates with Improved Blood Sugar Regulation.

PMID- 26199965
TI  - The evolution of MitraClip in the repair of mitral  regurgitation.

PMID- 26199967
TI  - Mole's Wow! So now you have your own lab!: Part III - The pact. By Caveman.

PMID- 26199966
TI  - Relationship between hospital PTCA volume and in-hospital outcomes.

PMID- 26199968
TI  - Estimation of waist and hip circumferences using body mass index in Delhi school
      girls (6-11 years).
AB  - Central obesity has been associated with the risk of cardiovascular and metabolic
      disease in children. A total of 358 Delhi school girls aged 6-11 years were
      measured for height, weight, waist circumference and hip circumference. The study
      demonstrates a linear correlation between body mass index (BMI) and waist and hip
      circumference and suggests an indirect method of estimating waist and hip
      circumferences, whose high values may be used for the diagnosis of metabolic
      syndrome and cardiovascular disease. Further investigations on different groups
      are needed to substantiate these results and attribute BMI a predictive value in
      the clinical setting for the risk and diagnosis of childhood obesity-related
      metabolic disorders.

PMID- 26199969
TI  - Parvovirus B19 diagnosed by bone marrow  biopsy.

PMID- 26199970
TI  - Reply: To PMID 24563499.

PMID- 26199971
TI  - Reply: To PMID 25618867.

PMID- 26199972
TI  - In reply.

PMID- 26199973
TI  - DO FEDERAL REGULATIONS HELP OR HINDER PATIENT DATA SECURITY? In the wake of the
      Anthem breach, hospital CISOs question the effectiveness of initiatives like
      HIPAA and meaningful use.

PMID- 26199974
TI  - ROUND TABLE: HOW TO PROTECT PATIENT DATA. A panel of hospital security experts
      sheds light on the biggest threats to patient privacy and what they're doing to
      safeguard medical records.

PMID- 26199975
TI  - The Conservatives remain in power.

PMID- 26199976
TI  - Maria and Tyrone Sevilla--a victory for compassion.

PMID- 26199977
TI  - Ethics in nursing.

PMID- 26199978
TI  - Workers' compensation in Queensland to be restored.

PMID- 26199979
TI  - Anthothecol-encapsulated PLGA nanoparticles inhibit pancreatic cancer stem cell
      growth by modulating sonic hedgehog pathway.
AB  - Anthothecol, a limonoid isolated from plant Khaya anthotheca (Meliaceae), is an
      antimalarial compound. The objectives of this study were to examine the molecular
      mechanisms by which anthothecol-encapsulated PLGA-nanoparticles (Antho-NPs)
      regulate the behavior of pancreatic cancer stem cells (CSCs). Antho-NPs inhibited
      cell proliferation and colony formation, and induced apoptosis in pancreatic CSCs
      and cancer cell lines, but had no effects on human normal pancreatic ductal
      epithelial cells. Antho-NPs inhibited self-renewal capacity of pancreatic CSCs
      isolated from human and Kras(G12D) mice. Furthermore, antho-NPs suppressed cell
      motility, migration and invasion by up-regulating E-cadherin and inhibiting N
      cadherin and Zeb1. In addition, Antho-NPs inhibited pluripotency maintaining
      factors and stem cell markers, suggesting their inhibitory role on CSC
      population. Anthothecol disrupted binding of Gli to DNA, and inhibited Gli
      transcription and Gli target genes. Our studies establish preclinical
      significance of Antho-NPs for the treatment and/or prevention of pancreatic
      cancer. FROM THE CLINICAL EDITOR: Despite medical advances, the prognosis of
      pancreatic cancer remains poor. The search for an effective treatment has been
      under intensive research for some time. In this article, the authors investigated
      the efficacy and mechanism of anthothecol (an antimalarial compound),
      encapsulated by PLGA nanoparticles (Antho-NPs), against pancreatic cancer cell
      lines. It was found that Antho-NPs acted via the Sonic hedgehog signaling pathway
      and inhibited cancer stem cell growth. These results have provided important
      basis for further clinical trials.

PMID- 26199980
TI  - Semaphorins and neuropilins expression in salivary gland tumors.
AB  - BACKGROUND: Salivary gland tumors (SGT) account for 3-10% of all head and neck
      neoplasms, and little is known about their angiogenic properties. Despite
      semaphorins and neuropilins have been demonstrated to be prognostic determinants
      in many human cancers, they remain to be investigated in SGT. Therefore, the
      objective of this study was to analyze the clinical significance of the
      expression of class 3 semaphorins A (Sema3A) and B (Sema3B) and neuropilins-1 (Np
      1) and neuropilins-2 (Np-2), in SGT. METHODS: Two hundred and forty-eight SGT
      were organized in tissue microarray paraffin blocks and expression of CD34,
      Sema3A, Sema3B, Np-1, and Np-2 was determined through immunohistochemistry. The
      immunoreactions were quantified using digital algorithms and the results
      correlated with clinicopathological parameters. RESULTS: Malignant tumors had an
      increased vascular density than their benign counterparts and their increased
      vascular area significantly correlated with recurrences (P < 0.05). Patients
      older than 40 years and the presence of recurrences determined an inferior
      survival rate (P = 0.0057 and P = 0.0303, respectively). In normal salivary
      glands, Np-1 and Np-2 expression was restricted to ductal cells, whereas Sema3A
      and Sema3B were positive in the serous acinar compartment. Tumors were positive
      for all markers and the co-expression of Np-1/Np-2 significantly correlated with
      the presence of paresthesia and advanced stages of the tumors (P = 0.01 and P =
      0.04, respectively). CONCLUSION: Sema3A, Sema3B, Np-1, and Np-2 may be involved
      in the pathogenesis of SGT, but their expression did not present a statistically
      significant prognostic potential in this study.

PMID- 26199981
TI  - The Association Between Vulvovaginal Atrophy Symptoms and Quality of Life Among
      Postmenopausal Women in the United States and Western Europe.
AB  - BACKGROUND: Vulvovaginal atrophy (VVA) is a condition associated with decreased
      estrogenization of the vaginal tissue, which can result in vaginal dryness,
      irritation, and dyspareunia. This study quantified the burden associated with VVA
      symptoms across the United States and Europe and compared this burden with other
      chronic conditions. METHODS: Data were analyzed from the International Women's
      Health Study, a cross-sectional Internet survey of women aged 40-75 years in the
      United States and Europe. All postmenopausal women aged 40-75 years were included
      in the analyses (Germany n=970, Spain n=294, France n=1054, Italy n=387, United
      Kingdom n=1096, United States n=3267). VVA symptom severity (none, mild,
      moderate, severe) was assessed using the Menopause Rating Scale and included in
      general linear models to predict EuroQol-5D (EQ-5D) quality of life scores.
      RESULTS: The prevalence of VVA symptoms varied between 40.00% (Germany) and
      54.42% (Spain), with half of women reporting their symptoms as either moderate or
      severe. Pooling data from all countries together, each incremental level of
      severity (none through severe) was associated with a significant decrement in EQ
      5D scores (none=0.84 vs. mild=0.81 vs. moderate=0.79 vs. severe=0.74; p<0.05).
      The decrements in EQ-5D scores associated with moderate to severe VVA symptoms
      were comparable to those observed in other serious conditions including
      arthritis, chronic obstructive pulmonary disease, asthma, and irritable bowel
      syndrome. CONCLUSIONS: VVA symptoms are associated with clinically meaningful
      decrements in quality of life that may be comparable to serious conditions such
      as arthritis, chronic obstructive pulmonary disease, asthma, and irritable bowel
      syndrome. Improved management of VVA symptoms may be required to alleviate the
      impact of VVA on the quality of life of affected women.

PMID- 26199982
TI  - Bioavailability of Pyrene Associated with Suspended Sediment of Different Grain
      Sizes to Daphnia magna as Investigated by Passive Dosing Devices.
AB  - Suspended sediment (SPS) is widely present in rivers around the world. However,
      the bioavailability of hydrophobic organic compounds (HOCs) associated with SPS
      is not well understood. In this work, the influence of SPS grain size on the
      bioavailability of SPS-associated pyrene to Daphnia magna was studied using a
      passive dosing device, which maintained a constant freely dissolved pyrene
      concentration (Cfree) in the exposure systems. The immobilization and protein as
      well as enzymatic activities of Daphnia magna were investigated to study the
      bioavailability of SPS-associated pyrene. With Cfree of pyrene ranging from 20.0
      to 60.0 MUg L(-1), the immobilization of Daphnia magna in the presence of 1 g L(
      1) SPS was 1.11-2.89 times that in the absence of SPS. The immobilization caused
      by pyrene associated with different grain size SPS was on the order of 50-100 MUm
      > 0-50 MUm > 100-150 MUm. When pyrene Cfree was 20.0 MUg L(-1), the
      immobilization caused by pyrene associated with 50-100 MUm SPS was 1.42 and 2.43
      times that with 0-50 and 100-150 MUm SPS, respectively. The protein and enzymatic
      activities of Daphnia magna also varied with the SPS grain size. The effect of
      SPS grain size on the bioavailability of SPS-associated pyrene was mainly due to
      the difference in SPS ingestion by Daphnia magna and SPS composition, especially
      the organic carbon type, among the three size fractions. This study suggests that
      not only the concentration but also the size distribution of SPS should be
      considered for the development of a biological effect database and establishment
      of water quality criteria for HOCs in natural waters.

PMID- 26199983
TI  - Airflow Limitation and Histology Shift in the National Lung Screening Trial. The
      NLST-ACRIN Cohort Substudy.
AB  - RATIONALE: Annual computed tomography (CT) is now widely recommended for lung
      cancer screening in the United States, although concerns remain regarding the
      potential harms, including those from overdiagnosis. OBJECTIVES: To examine the
      effect of airflow limitation on overdiagnosis by comparing lung cancer incidence,
      histology, and stage shift in a subgroup of the National Lung Screening Trial
      (NLST). METHODS: In an NLST subgroup (n = 18,714), screening participants were
      randomized to annual computed tomography (CT, n = 9,357) or chest radiograph (n =
      9,357) screening and monitored for a mean of 6.1 years. After baseline
      prebronchodilator spirometry, to identify the presence of airflow limitation,
      18,475 subjects (99%) were assigned as having chronic obstructive pulmonary
      disease (COPD) or no COPD. Lung cancer prevalence, incidence, histology, and
      stage shift were compared after stratification by COPD. MEASUREMENTS AND MAIN
      RESULTS: For screening participants with spirometric COPD (n = 6,436), there was
      a twofold increase in lung cancer incidence (incident rate ratio, 2.15; P <
      0.001) and, when compared according to screening arm, no excess lung cancers and
      comparable histology. Compared with chest radiography, there was also a trend
      favoring reduced late-stage and increased early-stage cancers in the CT arm (P =
      0.054). For those with normal baseline spirometry (n = 12,039), we found an
      excess of lung cancers during screening in the CT arm, almost exclusively early
      stage adenocarcinoma-related cancers (histology shift and overdiagnosis). After
      correction for these excess cancers, stage shift was marginal (P = 0.077).
      CONCLUSIONS: In the CT arm of the NLST-ACRIN (American College of Radiology
      Imaging Network) cohort, COPD status was associated with a doubling of lung
      cancer incidence, no apparent overdiagnosis, and a more favorable stage shift.

PMID- 26199985
TI  - Sexual Activity, Contraceptive Use, and Childbearing of Teenagers Aged 15-19 in
      the United States.
AB  - KEY FINDINGS: Monitoring sexual activity and contraceptive use among U.S.
      adolescents is important for understanding differences in their risk of
      pregnancy. In 2013, the U.S. birth rate for teenagers aged 15-19 dropped 57% from
      its peak in 1991 (1), paralleling a decline in the teen pregnancy rate (1-2). But
      these rates are still higher than those in other developed countries (3-4). Using
      data from the 1988 to 2011-2013 National Survey of Family Growth (NSFG), this
      report provides trends and recent national estimates of sexual activity,
      contraceptive use, and childbearing among teenagers aged 15-19.

PMID- 26199986
TI  - Chronic Pancreatitis and Fracture: A Retrospective, Population-Based Veterans
      Administration Study.
AB  - OBJECTIVES: There is increasing evidence that chronic pancreatitis (CP) is a risk
      factor for osteoporotic fracture, but data on males with CP and fracture
      prevalence are sparse. We determined the association of sex and age using a large
      Veterans Administration database. METHODS: This was a retrospective analysis
      (1998-2007). Patients with CP (International Classification of Diseases code
      577.1) and control subjects (without CP) were identified after exclusions and
      fracture prevalence (vertebral, hip, and wrist) were recorded. RESULTS: 453,912
      Veterans Administration patients were identified (control subjects: 450,655 and
      patients with CP: 3257). Mean ages of control subjects and CP were 53.6 and 54.2
      years (P < 0.014). Patients with CP had higher odds ratios of total fractures
      (2.35; 95% confidence interval [CI], 2.00-2.77), vertebral fracture 2.11 (95% CI,
      1.44-3.01), hip fracture 3.49 (95% CI, 2.78-4.38), and wrist fracture 1.68 (95%
      CI, 1.29-2.18) when compared with control subjects. After adjusting for age group
      and etiology, patients with CP had increased odds of total fractures, vertebral
      fractures, and hip fractures (P < 0.05). CONCLUSIONS: In this male-predominate
      Veterans Administration study, patients with CP were at increased risk of
      osteoporotic fractures. The risk was higher for hip fracture (>3 times) in
      patients with CP compared with control subjects. All patients with CP older than
      45 years, irrespective of sex, should be screened for bone mineral density loss.

PMID- 26199984
TI  - Chronic gastric electrical stimulation leads to weight loss via modulating
      multiple tissue neuropeptide Y, orexin, alpha-melanocyte-stimulating hormone and
      oxytocin in obese rats.
AB  - OBJECTIVES: Gastric electrical stimulation (GES) has great potential for the
      treatment of obesity. We investigated the impact of chronic GES on the alteration
      of adipose tissue and the regulation of neuropeptide Y (NPY), orexin (OX), alpha
      melanocyte-stimulating hormone (alpha-MSH) and oxytocin (OXT), and their
      receptors in several tissues. MATERIAL AND METHODS: Most of the experiments
      included three groups of diet-induced obesity rats: (1) sham-GES (SGES); (2) GL
      6mA (GES with 6 mA, 4 ms, 40 Hz, 2 s on, 3 s off at lesser curvature); and (3)
      SGES-PF (SGES rats receiving pair feeding to match the consumption of GL-6mA
      rats). Chronic GES was applied for 2 h every day for 4 weeks. During treatment
      with GES, food intake and body weight were monitored weekly. The alteration of
      epididymal fat weight, gastric emptying, and expression of peptides and their
      receptors in several tissues were determined. RESULTS: GL-6mA was more potent
      than SGES-PF in decreasing body weight gain, epididymal fat tissue weight,
      adipocyte size and gastric emptying. Chronic GES significantly altered NPY, OX,
      alpha-MSH and OXT and their receptors in the hypothalamus, adipose tissue and
      stomach. CONCLUSIONS: Chronic GES effectively leads to weight loss by reducing
      food intake, fat tissue weight and gastric emptying. NPY, alpha-MSH, orexin and
      OXT, and their receptors in the hypothalamus, adipose tissue and stomach appear
      to be involved in the anti-obesity effects of chronic GES.

PMID- 26199987
TI  - Synthesis of Thrombolytic Sol-Gel Coatings: Toward Drug-Entrapped Vascular
      Grafts.
AB  - As is evident from numerous investigations, drug-eluting vascular grafts and
      stents have not solved the main problems associated with thrombosis and due to
      drug release only postpone their advance for a longer period. Here we point to a
      potential solution of this problem by developing thrombolytic sol-gel coatings
      which potentially could lead to drug-entrapped vascular grafts: urokinase-type
      plasminogen activator was entrapped within a porous alumina sol-gel film with a
      subsequent deposition on a polymer graft. 

PMID- 26199988
TI  - Thalidomide Treatment of Pediatric Ulcerative Colitis: A New Use for an Old Drug.

PMID- 26199989
TI  - Strategies to Improve Influenza Vaccination in Pediatric Inflammatory Bowel
      Disease Through Education and Access.
AB  - BACKGROUND: Influenza vaccine uptake remains low in patients with inflammatory
      bowel disease despite an increased risk of complications from infection. We
      studied barriers to vaccination and evaluated the impact of an educational
      intervention and vaccine provision in pediatric patients with inflammatory bowel
      disease. METHODS: A prospective cohort study was completed over 2 successive
      influenza seasons. In year 1, we surveyed parents and patients aged 14 years or
      older regarding influenza vaccination. In year 2, before the influenza season,
      patients were provided with an educational module. After influenza vaccine
      availability, patients were offered both education and vaccine in clinic. Chi
      squared analysis was used to identify significant differences in vaccination
      rates in each intervention group. Demographic factors were associated with
      vaccination status. RESULTS: In year 1, 180 parents and 183 adolescents completed
      the survey. In year 1, 47% of patients obtained the influenza vaccine and 34% of
      patients reported obtaining the vaccine annually. Top reasons for nonvaccination
      were perceived lack of benefit (28%) and concerns about adverse events (19%). In
      year 2 (n = 228), the vaccination rate in patients who received the education
      alone was 75.0%, compared with 89.5% of patients who received both education and
      vaccine access in clinic (P = 0.0043). Among the patients who took part in both
      study years (n = 129), influenza vaccination rates increased from 45% in year 1
      to 82% in year 2 (P < 0.0001). CONCLUSIONS: The educational intervention was
      associated with improved influenza vaccination rates. Additional vaccine uptake
      was achieved with provision of influenza vaccination during clinic visits.

PMID- 26199990
TI  - Volatile Organic Compounds in Exhaled Air as Novel Marker for Disease Activity in
      Crohn's Disease: A Metabolomic Approach.
AB  - BACKGROUND: Disappearance of macroscopic mucosal inflammation predicts long-term
      outcome in Crohn's disease (CD). It can be assessed by ileocolonoscopy, which is,
      however, an invasive and expensive procedure. Disease activity indices do not
      correlate well with endoscopic activity and noninvasive markers have a low
      sensitivity in subgroups of patients. Volatile organic compounds (VOCs) in breath
      are of increasing interest as noninvasive markers. The aim of this study was to
      investigate whether VOCs can accurately differentiate between active CD and
      remission. METHODS: Patients participated in a 1-year follow-up study and Harvey
      Bradshaw index, blood, fecal, and breath samples were collected at regular
      intervals. Patients were stratified into 2 groups: active (fecal calprotectin
      >250 ug/g) or inactive (Harvey-Bradshaw index <4, C-reactive protein <5 mg/L, and
      fecal calprotectin <100 ug/g) disease. Breath samples were analyzed by gas
      chromatography-time-of-flight mass spectrometry. Random forest analyses were used
      to find the most discriminatory VOCs. RESULTS: Eight hundred thirty-five breath-o
      grams were measured, 140 samples were assigned as active, 135 as inactive
      disease, and 110 samples of healthy controls. A set of 10 discriminatory VOCs
      correctly predicted active CD in 81.5% and remission in 86.4% (sensitivity 0.81,
      specificity 0.80, AUC 0.80). These VOCs were combined into a single disease
      activity score that classified disease activity in more than 60% of the
      previously undetermined individuals. CONCLUSIONS: We showed that VOCs can
      separate healthy controls and patients with active CD and CD in remission in a
      real-life cohort. Analysis of exhaled air is an interesting new noninvasive
      application for monitoring mucosal inflammation in inflammatory bowel disease.

PMID- 26199991
TI  - Ulcerative Colitis Database: An Integrated Database and Toolkit for Gene Function
      and Medication Involved in Ulcerative Colitis.
AB  - BACKGROUND: Over the last decade, a massive amount of well-annotated genomic data
      has been accumulated on the pathogenesis and therapies for ulcerative colitis
      (UC). However, a comprehensive repository is not available yet. METHODS:
      Ulcerative Colitis Database (UCDB) was constructed using text mining followed by
      manually curating on the literature to collect the reliable information of UC
      related genes, drugs, and susceptibility loci. UC DNA microarray data were
      collected. R packages were used to implement gene expression analysis toolkit.
      RESULTS: UCDB includes 4 separate but closely related components: "UC GENE," "UC
      DRUG," "UC LOCUS," and "UC ANALYSIS." The UC GENE contains comprehensive
      information for 1151 UC-related genes manually curated from 2919 publications.
      The UC DRUG includes information for 248 drugs manually curated from 2344
      publications. "UC LOCUS" includes 110 UC susceptibility SNP loci, which were
      collected from 12 Genome-Wide Association Studies. A comprehensive expression
      quantitative trait loci browser was also implemented. The UC ANALYSIS is an
      expression analysis toolkit for 37 UC expression array data sets, which contains
      1098 samples. The toolkit can be used to do gene expression correlation,
      clustering, differentially expressed, and Gene Set Enrichment Analysis (GSEA).
      CONCLUSIONS: UCDB provides a comprehensive collection of well-curated UC-related
      genes and drugs, and straightforward interfaces for gene expression analyses.
      UCDB is a useful leading resource for both basic and clinical research and will
      benefit UC community worldwide. UCDB is freely accessible at
      http://seiwertlab.uchicago.edu/UCDB.

PMID- 26199993
TI  - Pathogenesis of Clostridium difficile Infection and Its Potential Role in
      Inflammatory Bowel Disease.
AB  - Colonization with toxigenic Clostridium difficile may be associated with a wide
      spectrum of clinical presentation ranging from asymptomatic carriage to mild
      diarrhea to life-threatening colitis. Over the last 15 years, there has been a
      marked increase in the incidence of C. difficile infection, which predominantly
      affects elderly patients on antibiotics. More recently, there has been
      significant interest in the association between inflammatory bowel disease (IBD)
      and C. difficile infection. This review article discusses in some detail current
      knowledge of the mechanisms by which C. difficile toxins may mediate mucosal
      inflammation, together with the role of cell wall components of the microorganism
      in disease pathogenesis. Innate and adaptive host responses to C. difficile
      toxins and other components are described and include consideration of the
      potential role of known mucosal changes in IBD that may lead to an enhanced
      inflammatory response in the presence of C. difficile infection. Recent studies,
      which have characterized resident microbiota that may mediate protection against
      colonization by C. difficile, including their mechanisms of action, are also
      discussed. This includes the role of bile acids and 7alpha-dehydroxylase
      expressing bacteria, such as Clostridium scindens. Recent studies suggest a
      higher carriage rate of C. difficile in patients with IBD. It is anticipated that
      future studies will determine the role of dysbiosis in IBD in predisposing to
      colonization with C. difficile. 

PMID- 26199992
TI  - Serum Proteome Profiles in Stricturing Crohn's Disease: A Pilot Study.
AB  - BACKGROUND: Crohn's disease (CD) is a form of inflammatory bowel disease with
      different described behaviors, including stricture. At present, there are no
      laboratory studies that can differentiate stricturing CD from other phenotypes of
      inflammatory bowel disease. We performed a pilot study to examine differences in
      the proteome among patients with stricturing CD, nonstricturing CD, and
      ulcerative colitis. METHODS: Serum samples were selected from the Ocean State
      Crohn's and Colitis Area Registry, an established cohort of patients with
      inflammatory bowel disease. Patients with CD with surgically resected stricture
      were matched with similar patients with CD without known stricture and with
      ulcerative colitis. Serum samples from each patient were digested and analyzed
      using liquid chromatography-mass spectrometry to characterize the proteome.
      Statistical analyses were performed to identify peptides and proteins that can
      differentiate CD with stricture. RESULTS: Samples from 9 patients in each group
      (27 total patients) were analyzed. Baseline demographic characteristics were
      similar among the 3 groups. We quantified 7668 peptides and 897 proteins for
      analysis. Receiver operating characteristic analysis identified a subset of
      peptides with an area under the curve greater than 0.9, indicating greater
      separation potential. Partial least squares discriminant analysis was able to
      distinguish among the three groups with up to 70% accuracy by peptides and up to
      80% accuracy by proteins. We identified the significantly different proteins and
      peptides and determined their function based on previously published literature.
      CONCLUSIONS: The serum of patients with stricturing CD, nonstricturing CD, and
      ulcerative colitis is distinguishable through proteomic analysis. Some of the
      proteins that differentiate the stricturing phenotype have been implicated in
      complement activation, fibrinolytic pathways, and lymphocyte adhesion.

PMID- 26199995
TI  - Navigating the Minefields of Medicine and Journalism.

PMID- 26199994
TI  - Development of a Reagentless Biosensor for Inorganic Phosphate, Applicable over a
      Wide Concentration Range.
AB  - A fluorescent reagentless biosensor for inorganic phosphate (Pi), based on the E.
      coli PstS phosphate binding protein, was redesigned to allow measurements of
      higher Pi concentrations and at low, substoichiometric concentrations of
      biosensor. This was achieved by weakening Pi binding of the previous biosensor,
      and different approaches are described that could enable this change in
      properties. The readout, providing response to the Pi concentration, is delivered
      by tetramethylrhodamine fluorescence. In addition to two cysteine mutations for
      rhodamine labeling at positions 17 and 197, the final variant had an I76G
      mutation in the hinge region between the two lobes that make up the protein. Upon
      Pi binding, the lobes rotate on this hinge and the mutation on the hinge lowers
      affinity ~200-fold, with a dissociation constant now in the tens to hundreds
      micromolar range, depending on solution conditions. The signal change on Pi
      binding was up to 9-fold, depending on pH. The suitability of the biosensor for
      steady-state ATPase assays was demonstrated with low biosensor usage and its
      advantage in ability to cope with Pi contamination. 

PMID- 26199996
TI  - A Trigonal Prismatic Mononuclear Cobalt(II) Complex Showing Single-Molecule
      Magnet Behavior.
AB  - Single-molecule magnets (SMMs) with one transition-metal ion often rely on
      unusual geometry as a source of magnetically anisotropic ground state. Here we
      report a cobalt(II) cage complex with a trigonal prism geometry showing single
      ion magnet behavior with very high Orbach relaxation barrier of 152 cm(-1). This,
      to our knowledge, is the largest reported relaxation barrier for a cobalt-based
      mononuclear SMM. The trigonal prismatic coordination provided by the macrocyclic
      ligand gives intrinsically more stable molecular species than previously reported
      SMMs, thus making this type of cage complexes more amendable to possible
      functionalization that will boost their magnetic anisotropy even further. 

PMID- 26199997
TI  - Multicenter study on caries risk assessment in Japanese adult patients.
AB  - OBJECTIVES: This study was conducted to identify significant risk factors for the
      onset and the accumulation of new caries in adult patients undergoing regular
      preventive therapy. METHODS: The data of 732 patients from nine Japanese general
      dental practices were retrospectively analyzed. Classification and regression
      tree (CART) analysis was applied to develop a caries prediction model using the
      following patient parameters: age, number of teeth with caries experience (DMFT),
      levels of mutans streptococci (SM) and lactobacilli (LB), saliva flow rate and
      buffer capacity, and compliance with a preventive program. Poisson regression
      analysis was conducted to identify factors affecting caries accumulation within
      three years. RESULTS: CART analysis identified patients at high risk for primary
      caries with an odds ratio of 3.08 (95%CI, 1.55-5.79; p=0.0018) according to SM
      levels and compliance; and those for secondary caries with an odds ratio of 3.69
      (95%CI, 2.29-5.91; p<0.0001) according to LB and SM levels. Poisson regression
      analyses showed that accumulation of primary caries was affected by compliance
      (p<0.001), SM (p<0.001) and LB (p=0.013). Accumulation of secondary caries was
      affected by DMFT (p<0.001), SM (p<0.001) and LB (p<0.001). CONCLUSIONS: CART is
      an important tool in identifying the risk of caries development in individual
      adult patients. Cariogenic bacteria are important factors for both the onset and
      accumulation of primary and secondary caries. CLINICAL SIGNIFICANCE:
      Participation in a regular preventive program limits the onset and the
      accumulation of primary caries in adult patients.

PMID- 26199998
TI  - A vision of graded hemispheric specialization.
AB  - Understanding the process by which the cerebral hemispheres reach their mature
      functional organization remains challenging. We propose a theoretical account in
      which, in the domain of vision, faces and words come to be represented adjacent
      to retinotopic cortex by virtue of the need to discriminate among homogeneous
      exemplars. Orthographic representations are further constrained to be proximal to
      typically left-lateralized language-related information to minimize connectivity
      length between visual and language areas. As reading is acquired, orthography
      comes to rely more heavily (albeit not exclusively) on the left fusiform region
      to bridge vision and language. Consequently, due to competition from emerging
      word representations, face representations that were initially bilateral become
      lateralized to the right fusiform region (albeit, again, not exclusively). We
      review recent research that describes constraints that give rise to this graded
      hemispheric arrangement. We then summarize empirical evidence from a variety of
      studies (behavioral, evoked response potential, functional imaging) across
      different populations (children, adolescents, and adults; left handers and
      individuals with developmental dyslexia) that supports the claims that
      hemispheric lateralization is graded rather than binary and that this graded
      organization emerges dynamically over the course of development. Perturbations of
      this system either during development or in adulthood provide further insights
      into the principles governing hemispheric organization. 

PMID- 26199999
TI  - Direct observation of vinyl hydroperoxide.
AB  - Many alkyl-substituted Criegee intermediates are predicted to undergo an
      intramolecular 1,4-hydrogen transfer to form isomeric vinyl hydroperoxide species
      (C[double bond, length as m-dash]COOH moiety), which break apart to release OH
      and vinoxy radicals. We report direct detection of stabilized vinyl
      hydroperoxides formed via carboxylic acid-catalyzed tautomerization of Criegee
      intermediates. A doubly hydrogen-bonded interaction between the Criegee
      intermediate and carboxylic acid facilitates efficient hydrogen transfer through
      a double hydrogen shift. Deuteration of formic or acetic acid permits migration
      of a D atom to yield partially deuterated vinyl hydroperoxides, which are
      distinguished from the CH3CHOO, (CH3)2COO, and CH3CH2CHOO Criegee intermediates
      by mass. Using 10.5 eV photoionization, three prototypical vinyl hydroperoxides,
      CH2[double bond, length as m-dash]CHOOD, CH2[double bond, length as m
      dash]C(CH3)OOD, and CH3CH[double bond, length as m-dash]CHOOD, are detected
      directly. Complementary electronic structure calculations reveal several reaction
      pathways, including the barrierless acid-catalyzed tautomerization reaction
      predicted previously and a barrierless addition reaction that yields hydroperoxy
      alkyl formate. 

PMID- 26200000
TI  - Endoscopic management of bariatric surgical complications.
AB  - PURPOSE OF REVIEW: Bariatric surgery is recognized as the most effective
      treatment against obesity as it results in significant weight reduction and a
      high rate of remission of obesity-related comorbidities. However, bariatric
      surgery is not uncommonly associated with complications and an endoscopic
      approach to management is preferred over surgical reintervention. This review
      illustrates the latest developments in the endoscopic management of bariatric
      surgical complications. RECENT FINDINGS: For successful management of
      complications, precipitating and perpetuating factors must be addressed in
      addition to directing therapy at the target pathology. Endoscopy is well
      tolerated even in the acute postoperative setting when performed carefully with
      CO2 insufflation. Chronic proximal staple-line leaks/fistulas frequently do not
      respond to primary closure with diversion therapy, and a new technique of
      stricturotomy has been reported to improve outcomes. Innovations in the field of
      transoral endoscopic instruments have led to the development of a single-session
      entirely internal endoscopic retrograde cholangiopancreatography by creating a
      gastrogastric anastomosis. SUMMARY: Endoscopy allows for early diagnosis and
      prompt institution of therapy and should, therefore, be the first-line
      intervention in the management of complications of bariatric surgery in patients
      who do not need urgent surgical intervention. Computed tomography-guided drainage
      may be necessary in patients with drainable fluid collections. VIDEO ABSTRACT:
      http://links.lww.com/COG/A11.

PMID- 26200001
TI  - Per oral endoscopic myotomy for the treatment of achalasia.
AB  - Per oral endoscopic myotomy (POEM) represents the culmination of natural orifice
      transluminal endoscopic surgery (NOTES) research, and its most successful
      application to date. Over a thousand POEMs have been performed globally with
      remarkable results in terms of clinical efficacy and safety. PURPOSE OF REVIEW:
      We examine the most recent literature concerning POEM since the last two
      comprehensive analyses [Natural Orifice Surgery Consortium for Assessment and
      Research (NOSCAR) White Paper, ASGE Preservation and Incorporation of Valuable
      endoscopic Innovations (PIVI)], and integrate this literature in the consensus
      POEM guidelines and perspective. These current works are largely centered on POEM
      operator learning curve, comparison of POEM and laparoscopic Heller myotomy (LHM)
      and extended application of POEM. RECENT FINDINGS: POEM and LHM are comparable in
      terms of efficacy (diminished dysphagia and Eckardt score) and complications
      including GERD. POEM has been successfully performed in a wide variety of
      patients including children, those with prior achalasia therapy and those with
      spastic esophageal disorders. SUMMARY: POEM has been validated as a treatment for
      achalasia. Issues remain regarding its longer term efficacy in comparison with
      LHM. Subsequent comparison trials are needed. VIDEO ABSTRACT:
      http://links.lww.com/COG/A14.

PMID- 26200003
TI  - Monitoring lipid peroxidation within foam cells by lysosome-targetable and
      ratiometric probe.
AB  - Lipid peroxidation (LPO) in lysosomes is a valuable analyte because it is close
      associated with the evolutions of some major diseases. As a typical example, in
      the start-up phase of atherosclerosis, lysosomes get as swollen as foams, by
      accumulating a large amount of lipoproteins, which facilitates the free-radical
      chain propagation of LPO. Despite the existences of several fluorescent LPO
      probes, they are not appropriate for reporting the local extents of lysosomal
      LPO, for their unspecific intracellular localizations. Here, Foam-LPO, the first
      fluorescent LPO probe specifically targeting lysosomes, has been developed
      through straightforward synthesis using low-cost reagents. A basic tertiary amine
      group enables it to selectively localize in acidic lysosomes; and the conjugated
      diene moiety within the BODIPY fluorophore will degrade in response to lipid
      peroxidation, which results in fluorescence maximum shifting from 586 to 512 nm.
      Thus, under a confocal fluorescence microscope, Foam-LPO is able not only to
      visualize dynamic morphological changes of lysosomes during the evolution of foam
      cells, but also to relatively quantify local LPO extents in single lysosomes
      through ratiometric imaging. In addition, Foam-LPO proves applicable for two
      color flow cytometry (FCM) analysis to make quantitative and high-throughput
      evaluation of LPO levels in large quantity of cells at different stages during
      the induction to form foam cells. Also importantly, with the aid of this new
      probe, the different roles played by low-density lipoprotein (LDL) and its
      oxidized form (ox-LDL) for the LPO processes of foam cells are distinguished and
      clarified, which benefits the understanding in the initiation and control factors
      of atherosclerosis. 

PMID- 26200002
TI  - Computer aided biomanufacturing of mechanically robust pure collagen meshes with
      controlled macroporosity.
AB  - Reconciliation of high strength and high porosity in pure collagen based
      structures is a major barrier in collagen's use in load-bearing applications. The
      current study developed a CAD/CAM based electrocompaction method to manufacture
      highly porous patterned scaffolds using pure collagen. Utilization of
      computerized scaffold design and fabrication allows the integration of mesh
      scaffolds with controlled pore size, shape and spacing. Mechanical properties of
      fabricated collagen meshes were investigated as a function of number of patterned
      layers, and with different pore geometries. The tensile stiffness, tensile
      strength and modulus ranges from 10-50 N cm(-1), 1-6 MPa and 5-40 MPa
      respectively for all the scaffold groups. These results are within the range of
      practical usability of different tissue engineering application such as tendon,
      hernia, stress urinary incontinence or thoracic wall reconstruction. Moreover, 3
      fold increase in the layer number resulted in more than 5-fold increases in
      failure load, toughness and stiffness which suggests that by changing the number
      of layers and shape of the structure, mechanical properties can be modulated for
      the aforementioned tissue engineering application. These patterned scaffolds
      offer a porosity ranging from 0.8 to 1.5 mm in size, a range that is commensurate
      with pore sizes of repair meshes in the market. The connected macroporosity of
      the scaffolds facilitated cell-seeding such that cells populated the entire
      scaffold at the time of seeding. After 3 d of culture, cell nuclei became
      elongated. These results indicate that the patterned electrochemical deposition
      method in this study was able to develop mechanically robust, highly porous
      collagen scaffolds with controlled porosity which not only tries to solve one of
      the major tissue engineering problems at a fundamental level but also has a
      significant potential to be used in different tissue engineering applications. 

PMID- 26200004
TI  - A Sense of Self: RIG-I's Tolerance to Host RNA.
AB  - The innate immune sensor RIG-I recognizes viral RNA while avoiding unwanted
      activation by self RNA. In this issue of Immunity, Schuberth-Wagner et al. (2015)
      show that a histidine residue in the RNA binding pocket of RIG-I sterically
      excludes the cap1 structure of self RNA, thereby preventing downstream
      activation.

PMID- 26200005
TI  - miR-155-SOCS1 as a Functional Axis: Satisfying the Burden of Proof.
AB  - The importance of individual target genes for miRNA activity has been difficult
      to establish. In this issue of Immunity, Lu et al. (2015) disrupt the miR-155
      binding site in the SOCS1 3' UTR in the mouse germline and show that this axis is
      important for T and NK cell function.

PMID- 26200006
TI  - Caught Off Center: Rethinking the Requirements for Antibody Affinity Maturation.
AB  - Antibody affinity maturation involves selective survival of high affinity B cells
      and is thought to require the germinal center (GC) microenvironment. In this
      issue of Immunity, Di Niro et al. (2015) challenge this view, showing that low
      affinity B cells initiate Salmonella responses and affinity mature outside of
      GCs.

PMID- 26200007
TI  - Stop Press: Eosinophils Drafted to Join the Th17 Team.
AB  - Eosinophils are commonly associated with Th2 cell-driven inflammation. In this
      issue of Immunity, Griseri et al. (2015) identify a new GM-CSF-dependent role for
      eosinophils in the pathogenesis of IL-23-Th17 cell-induced colitis.

PMID- 26200008
TI  - Passenger Mutations Identified in the Blink of an Eye.
AB  - Passenger mutations specific to particular mouse strains can distort experimental
      outcomes. In this issue of Immunity, Vanden Berghe et al. (2015) demonstrate that
      passenger mutations are frequent in most genetically engineered congenic mice and
      persist even after extensive backcrossing.

PMID- 26200009
TI  - Escaping Negative Selection: ILC You in the Gut.
AB  - How commensal-specific T cells are controlled in the periphery is poorly
      understood. In a recent issue of Science, Hepworth et al. (2015) show that ILC3s
      induce apoptosis of microbiota-specific CD4 T cells in a form of extrathymic
      negative selection.

PMID- 26200011
TI  - Barrier Epithelial Cells and the Control of Type 2 Immunity.
AB  - Type-2-cell-mediated immunity, rich in eosinophils, basophils, mast cells, CD4(+)
      T helper 2 (Th2) cells, and type 2 innate lymphoid cells (ILC2s), protects the
      host from helminth infection but also drives chronic allergic diseases like
      asthma and atopic dermatitis. Barrier epithelial cells (ECs) represent the very
      first line of defense and express pattern recognition receptors to recognize type
      2-cell-mediated immune insults like proteolytic allergens or helminths. These ECs
      mount a prototypical response made up of chemokines, innate cytokines such as
      interleukin-1 (IL-1), IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), as
      well as the alarmins uric acid, ATP, HMGB1, and S100 proteins. These signals
      program dendritic cells (DCs) to mount Th2-cell-mediated immunity and in so doing
      boost ILC2, basophil, and mast cell function. Here we review the general
      mechanisms of how different stimuli trigger type-2-cell-mediated immunity at
      mucosal barriers and how this leads to protection or disease. 

PMID- 26200010
TI  - Interferon-lambda: Immune Functions at Barrier Surfaces and Beyond.
AB  - When type III interferon (IFN-lambda; also known as interleukin-28 [IL-28] and IL
      29) was discovered in 2003, its antiviral function was expected to be analogous
      to that of type I IFNs (IFN-alpha and IFN-beta) via the induction of IFN
      stimulated genes (ISGs). Although IFN-lambda stimulates expression of antiviral
      ISGs preferentially in cells of epithelial origin, recent studies have defined
      additional antiviral mechanisms in other cell types and tissues. Viral infection
      models using mice lacking IFN-lambda signaling and SNP associations with human
      disease have expanded our understanding of the contribution of IFN-lambda to the
      antiviral response at anatomic barriers and the immune response beyond these
      barriers. In this review, we highlight recent insights into IFN-lambda functions,
      including its ability to restrict virus spread into the brain and to clear
      chronic viral infections in the gastrointestinal tract. We also discuss how IFN
      lambda modulates innate and adaptive immunity, autoimmunity, and tumor
      progression and its possible therapeutic applications in human disease. 

PMID- 26200012
TI  - Orphan Nuclear Receptor ERRalpha Controls Macrophage Metabolic Signaling and A20
      Expression to Negatively Regulate TLR-Induced Inflammation.
AB  - The orphan nuclear receptor estrogen-related receptor alpha (ERRalpha; NR3B1) is
      a key metabolic regulator, but its function in regulating inflammation remains
      largely unknown. Here, we demonstrate that ERRalpha negatively regulates Toll
      like receptor (TLR)-induced inflammation by promoting Tnfaip3 transcription and
      fine-tuning of metabolic reprogramming in macrophages. ERRalpha-deficient (Esrra(
      /-)) mice showed increased susceptibility to endotoxin-induced septic shock,
      leading to more severe pro-inflammatory responses than control mice. ERRalpha
      regulated macrophage inflammatory responses by directly binding the promoter
      region of Tnfaip3, a deubiquitinating enzyme in TLR signaling. In addition,
      Esrra(-/-) macrophages showed an increased glycolysis, but impaired mitochondrial
      respiratory function and biogenesis. Further, ERRalpha was required for the
      regulation of NF-kappaB signaling by controlling p65 acetylation via maintenance
      of NAD(+) levels and sirtuin 1 activation. These findings unravel a previously
      unappreciated role for ERRalpha as a negative regulator of TLR-induced
      inflammatory responses through inducing Tnfaip3 transcription and controlling the
      metabolic reprogramming.

PMID- 26200015
TI  - Angiotensin-converting enzyme gene polymorphism in Thai patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To determine the association between angiotensin-converting enzyme
      (ACE) I/D polymorphism and the presence of systemic lupus erythematosus (SLE)
      disease and lupus nephritis (LN), including the association with disease severity
      in a Thai population. METHOD: In this retrospective study, 187 SLE patients
      followed up for (at least) 7 years in a rheumatology clinic of an academic
      hospital were enrolled. Disease severity and damage score at diagnosis and every
      6 months, including treatment outcome of the first episode of LN were retrieved
      from medical records. The ACE genotype of SLE patients were determined by
      polymerase chain reaction and compared with ACE genotype in 687 controls from a
      database of a Thai surveillance cohort. RESULT: There was an association between
      ACE I/D polymorphism and the presence of SLE disease and LN (P < 0.001).
      Unexpectedly, the prevalence of DD genotype in SLE patients was lower than
      controls (OR 0.44 [95% CI 0.23-0.84], P = 0.013). The prevalence of ID genotype
      was not different between SLE patients and controls (OR 1.44 [95%CI 0.93-2.24], P
      = 0.102), but was higher in LN patients compared to controls (OR 1.77 [95% CI
      1.14-2.72], P = 0.01). However, the ACE I/D polymorphism is not associated with
      SLE disease severity, either in patients with or without nephritis. CONCLUSION:
      The DD genotype could not be used as a poor prognostic marker for SLE and LN
      susceptibility in a Thai population. However, ID genotype may be associated with
      risk to develop LN.

PMID- 26200013
TI  - An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic
      Inflammation by Promoting Regulatory T Cell Numbers.
AB  - House dust mite-derived proteases contribute to allergic disorders in part by
      disrupting epithelial barrier function. Interleukin-33 (IL-33), produced by lung
      cells after exposure to protease allergens, can induce innate-type airway
      eosinophilia by activating natural helper (NH) cells, a member of group 2 innate
      lymphoid cells (ILC2), to secrete Th2 type-cytokines. Because IL-33 also can
      induce mast cells (MCs) to secrete Th2 type-cytokines, MCs are thought to
      cooperate with NH cells in enhancing protease or IL-33-mediated innate-type
      airway eosinophilia. However, we found that MC-deficient Kit(W-sh/W-sh) mice
      exhibited exacerbated protease-induced lung inflammation associated with reduced
      numbers of regulatory T (Treg) cells. Moreover, IL-2 produced by IL-33-stimulated
      MCs promoted expansion of numbers of Treg cells, thereby suppressing development
      of papain- or IL-33-induced airway eosinophilia. We have thus identified a unique
      anti-inflammatory pathway that can limit induction of innate-type allergic airway
      inflammation mediated by NH cells. 

PMID- 26200014
TI  - Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote
      Interleukin-23 Driven Chronic Colitis.
AB  - The role of intestinal eosinophils in immune homeostasis is enigmatic and the
      molecular signals that drive them from protective to tissue damaging are unknown.
      Most commonly associated with Th2 cell-mediated diseases, we describe a role for
      eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte
      macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal
      inflammation was characterized by increased bone marrow eosinopoiesis and
      accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil
      depletion ameliorated colitis, implicating eosinophils in disease pathogenesis.
      GM-CSF was a potent activator of eosinophil effector functions and intestinal
      accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast
      neutrophil accumulation was GM-CSF independent and dispensable for colitis. In
      addition to TNF secretion, release of eosinophil peroxidase promoted colitis
      identifying direct tissue-toxic mechanisms. Thus, eosinophils are key
      perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune
      diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic
      target. 

PMID- 26200016
TI  - Muscular Strength and Power Correlates of Tackling Ability in Semiprofessional
      Rugby League Players.
AB  - This study investigated the relationship between muscular strength and power and
      tackling ability in semiprofessional rugby league players. Thirty-six
      semiprofessional (mean +/- SD age, 23.1 +/- 3.6 years) rugby league players, from
      3 distinct playing divisions (first grade, second grade, and under 20s),
      underwent tests of upper-body strength (3 repetition maximum [RM] bench press),
      lower-body strength (3RM squat), upper-body power (plyometric push-up [PPU]), and
      lower-body power (countermovement jump). Muscular strength relative to body mass
      was also calculated. Tackling ability of the players was tested using video
      analysis of a standardized one-on-one tackling drill. For all players, the
      strongest correlates of tackling ability were squat (r = 0.67), bench press (r =
      0.58), relative squat (r = 0.41), and PPU (r = 0.56). The strongest correlates of
      tackling ability in first grade players were squat (r = 0.72), bench press (r =
      0.72), relative squat (r = 0.86), and PPU (r = 0.70). For second grade players,
      only relative squat (r = 0.60) and PPU (r = 0.67) were associated with tackling
      ability. The strongest correlates of tackling ability in under 20s players were
      squat (r = 0.77), bench press (r = 0.70), and PPU (r = 0.65). The findings of
      this study demonstrate that muscular strength and upper-body power contribute to
      tackling ability in semiprofessional rugby league players. Therefore, as long as
      the technical aspects of tackling technique are adequately coached and practiced,
      then enhancements in muscular strength and power may serve as foundational
      components to underpin improvement in tackling ability.

PMID- 26200017
TI  - Lower Wingate Test Power Outcomes From "All-Out" Pretest Pedaling Cadence
      Compared With Moderate Cadence.
AB  - The aim of the present study was to determine the effect of different pretest
      pedaling cadences on power outcomes obtained during the Wingate Anaerobic Test
      (WAnT). Vigorously exercising adult men (n = 14, 24.9 +/- 1.2 years) and women (n
      = 14, 20.4 +/- 0.6 years) participated in a randomized crossover study during
      which they performed the 30-second WAnT on a mechanically braked cycle ergometer
      (0.075 kg.kg(-1) body weight) under 2 conditions. Participants pedaled maximally
      with an unloaded flywheel during 5 seconds before resistance was applied and the
      test began (FAST). In another trial, participants maintained a moderate cadence
      (80 revolutions per minute [rpm]) during 5 seconds before the test began (MOD).
      All other components of the WAnT were identical. Peak power (PP), mean power
      (MP), minimum power (MinP), fatigue index (%FAT), and maximum cadence during test
      were recorded. Comparisons were made using a 2 * 2 factorial repeated-measures
      analysis of variance. Regardless of gender, the FAST condition resulted in 22.2%
      lower PP (612.6 +/- 33.0 W vs. 788.3 +/- 43.5 W), 13.3% lower MP (448.4 +/- 22.2
      W vs. 517.2 +/- 26.4 W), 11.7% lower MinP (280.9 +/- 14.8 W vs. 318.3 +/- 17.2
      W), and 9.0% lower %FAT (53.5 +/- 1.3% vs. 58.8 +/- 1.5%) than MOD condition (p <
      0.01; mean +/- SD). Similar outcomes were observed within gender. The authors
      conclude that practitioners of the WAnT should instruct participants to maintain
      a moderate pedal cadence (~80 rpm) during 5 seconds before the test commences to
      avoid bias from software sampling and peripheral fatigue. Standardizing the
      pretest pedal cadence will be important to exercise testing professionals who
      compare data with norms or generate norms for specific populations.

PMID- 26200018
TI  - C-Alkynylation of Cyclopropanols.
AB  - Alkynylation of cyclopropanols with 1-bromo-1-alkynes has been devised for easy
      access to synthetically useful alk-4-yn-1-ones. This method broadens the utility
      of attractively functionalized cyclopropanols as a new class of homoenolate
      equivalent in C-C bond formation. 

PMID- 26200019
TI  - Sampling dynamic networks with application to investigation of HIV epidemic
      drivers.
AB  - We propose a method for randomly sampling dynamic networks that permits isolation
      of the impact of different network features on processes that propagate on
      networks. The new methods permit uniform sampling of dynamic networks in ways
      that ensure that they are consistent with both a given cumulative network and
      with specified values for constraints on the dynamic network properties.
      Development of such methods is challenging because modifying one network property
      will generally tend to modify others as well. Methods to sample constrained
      dynamic networks are particularly useful in the investigation of network-based
      interventions that target and modify specific dynamic network properties,
      especially in settings where the whole network is unobservable and therefore many
      network properties are unmeasurable. We illustrate this method by investigating
      the incremental impact of changes in networks properties that are relevant for
      the spread of infectious diseases, such as concurrency in sexual relationships.
      Development of the method is motivated by the challenges that arise in
      investigating the role of HIV epidemic drivers due to the often limited
      information available about contact networks. The proposed methods for randomly
      sampling dynamic networks facilitate investigation of the type of network data
      that can best contribute to an understanding of the HIV epidemic dynamics as well
      as of the limitations of conclusions drawn in the absence of such information.
      Hence, the methods are intended to aid in the design and interpretation of
      studies of network-based interventions. 

PMID- 26200022
TI  - International Association for Suicide Prevention.

PMID- 26200020
TI  - Recent advances in pediatric rheumatology: October-December 2014.

PMID- 26200023
TI  - Electrochemically Patterned Transducer with Anisotropic PEDOT through Liquid
      Crystalline Template Polymerization.
AB  - We have demonstrated patterning of highly ordered nanostructured conducting PEDOT
      (poly(3,4-ethylenedioxythiophene)) on glassy carbon electrode (GCE) through
      electrochemical polymerization of a biobased liquid crystalline template of EDOT
      PDPPA (3-pentadecylphenyl phosphoric acid). Self-assembled "EDOT-PDPPA" in water
      exhibited lyotropic liquid crystalline (LC) phases of nematic gyroid, columnar,
      and lamellar phases. Studies revealed that, during electrochemical
      polymerization, PEDOT-PDPPA mimicked the anisotropic domains of its monomer LC
      template. Nyquist plot showed enhancement in conductivity with a positive change
      in the HOMO- LUMO gap. Further, the efficiency of the modified GCE was
      demonstrated as an electrochemical transducer for the detection of nicotine. It
      was observed that oxidation of nicotine occurs at lower potential (0.83 V) with
      higher current (54.63 MUA) compared to bare GCE (1.1 V, 17.86 MUA) with nanomolar
      detection. This simple strategy of electrochemical patterning of conductive
      polymer on a conventional electrode can be exploited for the high tech
      applications in miniaturized plastronic devices. 

PMID- 26200024
TI  - When Frail Individuals or Their Families Request Nonindicated Interventions:
      Usefulness of the Four-Box Ethical Approach.
AB  - In the age of person-centered care, there is an emphasis on promoting patient
      autonomy and surrogate decision maker authority in making treatment decisions
      that are aligned with the patient's priorities and values. As technological
      advances offer multiple clinical options with various levels and types of risks
      and benefits, person-centered clinical practice encourages the incorporation of
      patients' and families' heterogeneous experiences into decisions regarding
      illness management. In caring for frail elderly adults, clinicians are sometimes
      faced with situations in which individuals and their surrogate decision-makers
      request a treatment that the clinicians feel is clinically inappropriate. This
      article provides a case example of a frail older adult with advanced chronic
      kidney disease who requests dialysis despite the advice of his nephrologist to
      pursue conservative management. The four-box approach, which provides clinicians
      with a structured ethical framework to facilitate informed and ethically
      justified treatment decisions, is then introduced. By considering the patient's
      medical indications, preferences, quality of life, and contextual factors, how
      each consideration plays a unique yet equally important role in informing
      clinically responsible and person-centered care is illustrated. 

PMID- 26200025
TI  - [Clinical usefulness of triazole derivatives in the management of fungal
      infections].
AB  - Current therapy for mycoses is limited to the use of a relative reduced number of
      antifungal drugs. Although amphotericin B still remains considered as the "gold
      standard" for treatment, acute and chronic toxicity, such as impairment of renal
      function, limits its use and enhances the investigation and clinical use other
      chemical families of antifungal drugs. One of these chemical class of active
      drugs are azole derivatives, discovered in 70s and introduced in clinical
      practice in 80s. Being the most prolific antifungal class, investigation about
      more molecules, with a safer and better pharmacological profile, active against a
      wide spectrum of fungi, with a wide range of administration routes gives us some
      azole representatives. 

PMID- 26200026
TI  - [Variability in antibiotic consumption within a regional health service,
      according to health area and model of healthcare coverage: national health system
      vs. civil servants' mutual insurance society].
AB  - INTRODUCTION: The aim of this study is to describe antibiotic consumption in the
      Region of Murcia in 2011, within the Spanish and European context, as well as to
      analyze the differences within the Region, both between health areas, and between
      users of the regional health service and those protected by the civil servants'
      mutual insurance society (MUFACE). METHODS: Retrospective observational study of
      prescriptions dispensed by the pharmacies in the Region of Murcia during 2011.
      Consumption rates were expressed as defined daily doses (DDD) per 1,000
      inhabitants/day and standardized consumption ratios (SCR). RESULTS: Overall
      antibiotics consumption rate in the Region of Murcia in 2011 was 30.05 DDD/1000/
      day (DID), which is much above the average rate for Spain (20.9 DID) and for the
      European Union (21.57 DID). Health areas within the Region with the highest and
      lowest consumption rate are, respectively, Vega Alta (SCR: 124.44; CI95% 124.26
      to 124.61) and Cartagena (SCR:84.16; CI95% 84.10 to 84.22). Civil servants
      covered by the mutual society have higher consumption rates than users of the
      regional health service (SCR: 105.01; CI95% 104.86 to 105.17). CONCLUSIONS: There
      is a high level of antibiotic prescription in the Region of Murcia Region in
      relative terms. A great variability in antibiotics consumption was observed
      between the different health areas, which might be related to the higher rate of
      the frequency of visits. The highest amount of variability in antibiotics
      prescription was found in cephalosporins and macrolides.

PMID- 26200027
TI  - [Safety of influenza vaccines in risk groups: analysis of adverse events
      following immunization reported in Valencian Community from 2005 to 2011].
AB  - OBJECTIVE: To evaluate reports of adverse events following influenza immunization
      by sex, risk and age groups in Valencian Community from 2005 to 2011. METHODS: A
      pharmacoepidemiological descriptive cross-sectional observational study based on
      the reports of adverse events following immunization (AEFI) against influenza,
      registered through the Vaccination Information System (SIV) of Valencian
      Community from 1 January 2005 until 31 December 2011 was done. RESULTS: During
      the study period 5,107,790 doses of vaccine against influenza were reported, with
      an AEFI incidence of 1.94 per 100,000 (95% CI 1.59 to 2.36), and 228,094 doses of
      vaccine for influenza A (H1N1) pdm09 (96.45 per 100,000, 95%CI 84.52-110.06). The
      70.71% (70) and 64.55% (142), respectively, of AEFI were in women. The healthcare
      workers group had a higher reporting rate for seasonal influenza (25.35 per
      100,000; 95%CI: 17.65-36.40) and for influenza A(H1N1) pdm09 (864.13 per 100,000;
      95%CI 714.38-1044.93) during the study period. CONCLUSIONS: Vaccines against
      influenza administered during the study had a high safety profile in both
      populations with disease risk and other susceptible target groups of vaccination.
      Adverse reactions reported during the study mostly coincide with those described
      in the summary of product characteristics of vaccines.

PMID- 26200028
TI  - Maraviroc modifies gut microbiota composition in a mouse model of obesity: a
      plausible therapeutic option to prevent metabolic disorders in HIV-infected
      patients.
AB  - INTRODUCTION: The proportion of HIV-infected patients with overweight/obesity has
      increased in recent years. These patients have an increased
      metabolic/cardiovascular risk compared with non-obese patients. Modulation of gut
      microbiota composition arises as a promising tool to prevent the development of
      obesity and associated disorders. The aim of this study was to investigate the
      impacts of maraviroc (MVC), a CCR5 antagonist approved for clinical use in HIV
      infected patients, on gut microbiota composition in a mouse model of obesity.
      METHODS: Thirty two male C57BL/6 mice were assigned to:a) Control (chow diet), b)
      MVC (chow diet plus 300 mg/L MVC), c) High-fat diet (HFD) or d) HFD/MVC (HFD plus
      300 mg/L MVC) groups. Body weight and food intake was recorded every 2-3 days.
      Mice were euthanized after 16 weeks of treatment and cecal contents were removed
      to analyse by real-time PCR four bacterial orders from the most dominant phyla in
      gut. RESULTS: Mice fed with a HFD showed a significant increase in
      Enterobacteriales (p<0.001 vs. control). MVC treatment induced a significant
      decrease in control (p<0.05) and HFD fed mice (p<0.001). Interestingly, this
      order was positively associated with body weight gain, insulin resistance and
      fatty liver. HFD induced a significant decrease in Bacteroidales and
      Clostridiales levels (p<0.05 and p<0.01, respectively). MVC decreased the
      presence of Bacteroidales (p<0.05 vs. control) while an increase was observed in
      HFD/MVC mice (p=0.01 vs. HFD). No direct effects of MVC were observed on
      Clostridiales and Lactobacillales. CONCLUSIONS: MVC may constitute a new
      therapeutic option to prevent obesity and related disorders in HIV-infected
      patients.

PMID- 26200030
TI  - [In vitro antifungal susceptibility profile of Scopulariopsis brevicaulis
      isolated from onychomycosis].
AB  - We studied the in vitro antifungal activity profile of amorolfine (AMR),
      bifonazole (BFZ), clotrimazole (CLZ), econazole (ECZ), fluconazole (FNZ),
      itraconazole (ITZ), ketoconazole (KTZ), miconazole (MNZ), oxiconazole (OXZ),
      tioconazole (TCZ) and terbinafine (TRB) against 26 clinical isolates of
      Scopulariopsis brevicaulis from patients with onychomycosis by means of an
      standardized microdilution method. Although this opportunistic filamentous fungi
      was reported as resistant to several broad-spectrum antifungals agents, obtained
      data shows a better fungistatic in vitro activity of AMR, OXZ and TRB (0.08, 0.3,
      and 0.35 mg/L, respectively) in comparison to that of CLZ (0.47 mg/L), ECZ (1.48
      mg/L), MNZ (1.56 mg/L, BFZ (2.8 mg/L), TCZ (3.33 mg/L), KTZ (3.73 mg/L). FNZ
      (178.47 mg/L) and ITZ (4.7 mg/L) showed a reduced in vitro antifungal activity
      against S. brevicaulis. Obtained MICs show the low in vitro antifungal
      susceptibility of S. brevicaulis to topical drugs for onychomycosis management,
      with exceptions (AMR, OZX and TRB). 

PMID- 26200029
TI  - Characterization of daptomycin non-susceptible Enterococcus faecium producing
      urinary tract infection in a renal transplant recipient.
AB  - OBJECTIVES: Characterization of a urine isolate of daptomycin non-susceptible
      Enterococcus faecium recovered from a patient with kidney transplantation and no
      history of daptomycin exposure. METHODS: After isolation in a urine sample,
      identification of E. faecium was confirmed by amplification of the E. faecium
      specific gene encoding D-alanyl-D-alanine ligase (ddl) and daptomycin
      susceptibility testing was performed by E-test on cation-adjusted Mueller-Hinton
      agar. In order to determine the genetic bases of daptomycin resistance, the open
      reading frames of five genes previously associated with daptomycin resistance in
      enterococci were sequenced. RESULTS: Substitutions in the response regulator LiaR
      (S19F) and cardiolipin synthase (R218Q) were identified. CONCLUSIONS: To the best
      of our knowledge, this is the first characterization of emerging daptomycin
      resistance in E. faecium in a Spanish hospital in the absence of daptomycin
      exposure and in a renal transplant recipient.

PMID- 26200031
TI  - Could ceftaroline be an alternative therapy for linezolid resistant
      Staphylococcus epidermidis infections in Intensive Care Medicine?
AB  - INTRODUCTION: Coagulase negative Staphylococcus continues generating interest in
      critically ill patients, due to their infections in extended admissions, in
      instrumented patients and due to their described multidrug resistance, which
      include glycopeptide heterorresistance and the increase in oxazolidinone
      resistance. Ceftaroline is a new cephalosporin with activity against resistant
      gram-positives, which, being betalactam, may provide adequate safety profile in
      the critical ill patient. The aim of this study was to determine the activity of
      ceftaroline and other antimicrobial agents against methicillin and linezolid
      resistant Staphylococcus epidermidis. MATERIAL AND METHODS: We studied
      susceptibility of ceftaroline, tigecycline, daptomycin and vancomycin in a total
      of sixty-eight methicillin and linezolid-resistant S. epidermidis isolates with
      clinical significance from an Intensive Care Unit, using E-test. RESULTS: All
      strains were susceptible to the four antimicrobial agents, regardless of the
      level of resistance to linezolid. CONCLUSION: Ceftaroline could be an alternative
      in the treatment of methicillin and linezolid-resistant S. epidermidis infections
      in critically ill patients.

PMID- 26200032
TI  - [Tracheobronchitis by Elizabethkingia meningoseptica in a patient with
      tracheostomy].

PMID- 26200033
TI  - [Mycotic aneurysm caused by Salmonella enteritidis: a case report].

PMID- 26200034
TI  - [Bacterial meningitis caused by Streptococcus pyogenes].

PMID- 26200035
TI  - [Detection of respiratory syncytial virus in the conjunctiva of a child with
      bronchiolitis caused by this virus].

PMID- 26200036
TI  - Aldosterone Synthase Promoter Polymorphism and Cardiovascular Phenotypes in a
      Large, Multiethnic Population-Based Study.
AB  - BACKGROUND: A single-nucleotide polymorphism in the aldosterone synthase gene
      (CYP11B2) promoter [-344C/T, rs1799998] has been reported to associate with
      cardiovascular phenotypes. METHODS: The Dallas Heart Study is a large,
      multiethnic cohort with a high prevalence of hypertension. We genotyped 3452
      Dallas Heart Study participants for -344C/T. Generalized linear models were used
      to assess whether variation at -344C/T associated with plasma aldosterone
      concentration (PAC), systolic and diastolic blood pressure (SBP and DBP), plasma
      glucose (in persons with no diabetes), HOMA IR (Homeostasis Model Assessment as
      an Index of Insulin Resistance), and left ventricular (LV) mass indexed to
      height. Systolic blood pressure and DBP were significantly higher in blacks
      compared with whites (P < 0.001 for SBP and for DBP) and Hispanics (P < 0.001 for
      SBP and for DBP). Log-transformed body mass index was also significantly higher
      in blacks compared with whites (P < 0.001), but not Hispanics (P = 0.10). Log
      transformed PAC was higher in whites compared with blacks (P < 0.001), but did
      not differ significantly in whites compared with Hispanics (P = 0.73). In
      univariate and multivariable analysis, -344C/T was not significantly associated
      with PAC within any ethnicity. In univariate and multivariable analysis, -344C/T
      was not associated with SBP or DBP within any ethnicity. After adjustment for
      multiple testing, univariate and multivariable analyses revealed no association
      between -344C/T and plasma glucose in patients with no diabetes, HOMA IR, or LV
      mass indexed to height. CONCLUSIONS: We were unable to reproduce previously
      reported associations between -344C/T and PAC, blood pressure, plasma glucose, or
      LV mass. Methodological differences might explain the differences between our
      findings and those previously reported.

PMID- 26200037
TI  - Elevated Human Endothelial Cell-Specific Molecule-1 Level and Its Association
      With Coronary Artery Disease in Patients With Hypertension.
AB  - BACKGROUND: Endothelial dysfunction plays an important role in the
      pathophysiology of coronary artery disease (CAD). Previous studies suggested that
      human endothelial cell-specific molecule-1 (endocan) may be a novel endothelial
      dysfunction marker. This study aims to investigate the relationship between serum
      endocan level and the presence and severity of CAD in patients with hypertension.
      METHODS: A total of 190 eligible hypertension patients were enrolled in this
      study. Serum endocan level was measured by enzyme-linked immunosorbent assay. The
      presence and severity of CAD were evaluated by coronary angiography. RESULTS:
      Hypertensive patients with CAD had significantly higher serum endocan level than
      those without CAD (1.63 +/- 0.51 ng/mL vs 1.31 +/- 0.65 ng/mL, P < 0.05).
      Multivariate logistic regression revealed that serum endocan level was
      independently associated with the presence of CAD (odds ratio, 2.662; 95%
      confidence interval, 1.560-4.544; P < 0.001). Spearman rank correlation analysis
      demonstrated that serum endocan level was associated with SYNergy between PCI
      with TAXUS and Cardiac Surgery score (r = 0.349, P = 0.001). CONCLUSIONS: Serum
      endocan level is independently correlated with the presence and severity of CAD
      in hypertension patients, and those with high endocan level may have an increased
      risk of developing atherosclerosis.

PMID- 26200038
TI  - Comparison of Dexmedetomidine versus Propofol for Sedation after
      Uvulopalatopharyngoplasty.
AB  - BACKGROUND: Adequate sedation is important in the post-anesthesia care unit
      (PACU) following uvulopalatopharyngoplasty (UPPP) to ensure patient comfort and
      decrease the duration of mechanical ventilation (MV), PACU stay, and bleeding.
      This study aimed to compare dexmedetomidine and propofol as sedatives after UPPP
      in the PACU. MATERIAL AND METHODS: We randomized 124 mechanically ventilated
      adults following UPPP who were managed in the PACU of the General Hospital of the
      Shenyang Military Region between January 2014 and June 2014, to receive either
      dexmedetomidine or propofol. The patients in the propofol group received an
      infusion of propofol (3 mg/kg/h) titrated up to 6 mg/kg/h to attain a Ramsay
      sedation score >=4. The dexmedetomidine group patients received 1.0 MUg/kg of
      dexmedetomidine over a period of 10 minutes and then 0.5 to 1.0 MUg/kg/h infusion
      to maintain a Ramsay sedation score >=4. RESULTS: Bispectral index (BIS) values
      were significantly lower in the dexmedetomidine group than in the propofol group
      at Ramsay sedation scores of 4 and 5. The mean times to spontaneous breathing,
      waking, and extubation were shorter in the dexmedetomidine group. Tramadol
      requirement was significantly reduced in the dexmedetomidine group (P<0.05).
      Incidence of cough during the extubation process in the propofol group was higher
      than in the dexmedetomidine group. After extubation, Bruggemann comfort scale
      (BCS) and Rass agitation scores (RASS) were decreased in the dexmedetomidine
      sedated patients. CONCLUSIONS: Dexmedetomidine provides safe and effective
      sedation for post-UPPP surgical patients and significantly reduces the use of
      analgesics, with minimal adverse effects.

PMID- 26200039
TI  - Use and reporting of restricted randomization: a review.
AB  - RATIONALE, AIMS AND OBJECTIVES: Restricted randomization, such as blocking or
      minimization, allows for the creation of balanced groups and even distribution of
      covariates, but it increases the risk of selection bias and technical error.
      Various methods are available to reduce these risks but there is limited evidence
      about their current usage, and there are also indications that reporting of these
      methods may not be adequate. This review aims to identify how frequently
      different methods of restriction are being used and to assess the reporting of
      these methods against established reporting standards. METHODS: 82 reports of
      randomized controlled trial were reviewed. For each trial, the reported method of
      randomization was recorded and the reporting of randomization was assessed. Where
      the method of randomization was not clear from the main paper, protocols and
      other published materials were also reviewed, and authors were contacted for
      further information. RESULTS: For 11% of trials the method of randomization was
      not reported in either the paper or a published protocol, and in a further 39% of
      cases the report omitted key details so that the predictability of the method
      could not be evaluated. In total, 88% of trials appear to have used some form of
      restricted randomization, and all of those that report the exact methods used
      either blocking or minimization. 15% of trials reported using blocks of six or
      less and 4% used minimization with no random element reported, both of which are
      highly predictable. CONCLUSION: Our results indicate that the majority of trials
      use some form of restriction, with many using relatively predictable methods that
      put them at greater risk of selection bias and technical error. Reporting of
      randomization methods often falls short of the minimum requirements set out by
      the CONSORT statement, leaving the reader unable to make an informed judgement
      about the risk of bias.

PMID- 26200041
TI  - [Depression Treatment in Old Age].

PMID- 26200042
TI  - [The Neuroleptic Malignant Syndrome].
AB  - BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare but potentially life
      threatening medication-induced syndrome. Core symptoms are hyperthermia,
      diaphoresis, rigidity, impaired consciousness, and creatinine kinase elevation.
      Additionally, patients show vegetative dysregulation including blood pressure
      fluctuations. The purpose of this paper is to summarize current findings, to
      facilitate diagnostics and to distinguish NMS from other syndromes. METHODS: We
      performed a systematic review of the literature. We included scientific
      publications, books and guidelines. RESULTS: In this review we summarize the
      current diagnostic criteria, differential diagnosis, pathogenesis and therapeutic
      options. CONCLUSION: Clinical symptoms of NMS are heterogeneous and it is
      difficult to diagnose early states. Early interventions are important to ensure
      fast and complete recovery. Since NMS is a rare condition, publications on NMS
      therapy are based on single-case reports, meta-analysis or expert opinions. Core
      symptoms should be considered: Exposure to dopamine-antagonists, hyperthermia,
      diaphoresis, rigidity, mental status alteration, creatinine kinase elevation, and
      vegetative dysregulation.

PMID- 26200040
TI  - Efficacy of the Natural Clay, Calcium Aluminosilicate Anti-Diarrheal, in Reducing
      Medullary Thyroid Cancer-Related Diarrhea and Its Effects on Quality of Life: A
      Pilot Study.
AB  - INTRODUCTION: Medullary thyroid cancer (MTC)-related diarrhea can be
      debilitating, reduces quality of life (QOL), and may be the only indication for
      initiating systemic therapy. Conventional antidiarrheal drugs are not always
      helpful and may have side effects. Calcium aluminosilicate antidiarrheal (CASAD),
      a natural calcium montmorrilonite clay, safely adsorbs toxins and inflammatory
      proteins associated with diarrhea. It was hypothesized that CASAD would reduce
      the severity of diarrhea and improve QOL in MTC patients. METHODS: This was a
      prospective pilot trial (NCT01739634) of MTC patients not on systemic therapy
      with self-reported diarrhea of three or more bowel movements (BMs) per day for a
      week or more. The study design included a one-week run-in period followed by one
      week of CASAD +/- a two-week optional continuation period. The primary endpoint
      was efficacy of one week of CASAD treatment in decreasing the number of BMs per
      day by >=20% when compared with the baseline run-in period. Secondary objectives
      included tolerability and safety and the impact on QOL using the MD Anderson
      Symptom Inventory-Thyroid questionnaire (MDASI-THY). RESULTS: Ten MTC patients
      (median age = 52 years, 70% female, 80% white) were enrolled. All had distant
      metastases, and median calcitonin was 5088 ng/mL (range 1817-42,007 ng/mL).
      Ninety percent had received prior antidiarrheals, and 40% of these had used two
      or more drugs, including tincture of opium (30%), loperamide (50%),
      diphenoxylate/atropine (20%), colestipol (10%), or cholestyramine (10%). Of seven
      evaluable patients, four (56%) had >=20% reduction in BMs per day. Six out of
      seven patients discontinued their prior antidiarrheals. Best response ranged from
      7% to 99% reduction in mean BMs/day from baseline. Five out of seven patients
      considered CASAD a success, and they opted for the two-week continuation period.
      Improvements in diarrhea and all six interference items assessed by MDASI-THY
      were noted at weeks 1 and 3. Total interference score was significantly improved
      at three weeks compared with baseline (p = 0.05). An oral levothyroxine
      absorption test was performed in one patient; malabsorption of levothyroxine was
      not observed. Adverse events included flatulence (40%), bloating (10%), heartburn
      (10%), and constipation (10%). CONCLUSIONS: CASAD is a promising strategy for
      treatment of MTC-related diarrhea. In this small pilot study, improvements in
      frequency and quality of diarrhea as well as QOL were noted. Further studies in
      this population are warranted.

PMID- 26200043
TI  - [Treating Late Life Depression with Antidepressants--A Summary of Recommendations
      in International Guidelines].
AB  - Late life depression is associated with severe health consequences, e.g. elevated
      risk of medical comorbidity and decreased quality of life. This paper summarizes
      the recommendations of the international guidelines on evidence-based
      pharmacological treatment of depression in late life in a systematic review.
      Pharmacological treatments for depression recommended by most of the guidelines,
      however, hardly address the issue of the possible side effects of antidepressants
      and other factors of multi-medication on the elderly. Different guidelines pay
      different degrees of attention to the specific group of geriatric patients. There
      is a lack of evidence-based treatment recommendation that takes into
      consideration the specific age-related issues of sensitivity to adverse effects
      or pharmacokinetic interaction. Further research is required to provide a
      database for more refined recommendations in guidelines.

PMID- 26200044
TI  - [Mycoplasma Pneumoniae-Induced Meningoencephalitis].
AB  - In clinical practice, secondary infections of the central nervous system (CNS)
      represent rare yet severe complications of their respective primary infections.
      In this case report, we describe a 22-year-old patient with a medical history of
      Asthma bronchiale, who developed significant neurological deficits after a
      respiratory infection. The neurological symptoms progressed despite antibiotic
      therapy with vancomycin, ampicillin and ceftriaxone. The patient's cerebrospinal
      fluid and a cranial magnetic resonance imaging (MRI) furnished evidence of acute
      meningoencephalitis. Microbiological assessment confirmed an acute mycoplasma
      pneumonia infection. Changing the patient's antibiotic regimen to minocycline and
      prednisolone led to significant clinical improvement. Pathomechanisms and
      therapeutic options to treat meningoencephalitis will be discussed in the
      following. 

PMID- 26200045
TI  - [A Pair of Siblings with a rare R5H-Mutation in Exon 1 of the MAPT-Gene].
AB  - We report on a female patient presenting with primary progressive aphasia (PPA)
      and her brother presenting with psychosis. Both siblings had an R5H-mutation in
      exon 1 of the MAPT-gene. The PPA patient presented for the first time at the age
      of 72 years with a 4-year-history of language impairment. After a progressive
      course the patient died at the age of 76 years. The R5H-MAPT-gene mutation
      detected in the siblings has been described only once in 2002 by Hayashi et al.
      [1]. In this previous case from Japan, a 75-year-old patient initially displayed
      amnesia and disorientation. He became bedridden, with progressive mutism and
      rigidity of the upper extremities. Noteworthy are the manifold signs and symptoms
      in R5H-mutations and the late age of onset. For future trials, the detection of
      biomarkers for frontotemporal lobar degeneration in presymptomatic cohorts like
      the genetic frontotemporal dementia initiative (GENFI) is of help for stratifying
      subjects at risk. 

PMID- 26200046
TI  - [Drug Strategies in the Treatment of Chronic Pain: Fokus on Hyperalgesic
      Effective Strategies].
AB  - Throughout Europe, chronic pain syndromes occur with a point prevalence of about
      20%, with somatic, psychological, and social factors playing a significant role
      for their development. Therefore, a careful evaluation of the interaction of
      these factors is the decisive step for a successful therapy. New insights into
      pathophysiological processes associated with chronic pain have led to an
      increasing differentiation of drug and non-drug strategies. These strategies take
      individual factors into account and aim on influencing the neural network for
      chronic pain. The drugs used are chosen on the basis of pathophysiological
      findings and specific drug effects. Adjunctive agents are often used in the
      management of chronic pain. Knowledge of anti-allodynic and anti-hyperalgesic
      drugs such as antidepressants and anticonvulsants increases continuously and is
      therefore presented in more detail in the present study. 

PMID- 26200047
TI  - Mapping the affective syndrome in Alzheimer's disease.

PMID- 26200048
TI  - Cortical correlates of affective syndrome in dementia due to Alzheimer's disease.
AB  - Neuropsychiatric symptoms in Alzheimer's disease (AD) are prevalent, however
      their relationship with patterns of cortical atrophy is not fully known.
      Objectives To compare cortical atrophy's patterns between AD patients and healthy
      controls; to verify correlations between neuropsychiatric syndromes and cortical
      atrophy. Method 33 AD patients were examined by Neuropsychiatric Inventory (NPI).
      Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI
      syndromes: affective, apathy, hyperactivity and psychosis. Correlations between
      structural imaging and neuropsychiatric scores were performed by Freesurfer.
      Results were significant with a p-value < 0.05, corrected for multiple
      comparisons. Results Patients exhibited atrophy in entorhinal cortices, left
      inferior and middle temporal gyri, and precuneus bilaterally. There was
      correlation between affective syndrome and cortical thickness in right frontal
      structures, insula and temporal pole. Conclusion Cortical thickness measures
      revealed atrophy in mild AD. Depression and anxiety symptoms were associated with
      atrophy of right frontal, temporal and insular cortices. 

PMID- 26200049
TI  - EGFR, p53, IDH-1 and MDM2 immunohistochemical analysis in glioblastoma:
      therapeutic and prognostic correlation.
AB  - We studied 36 glioblastoma cases at HC-UNICAMP from 2008 to 2012 and classified
      the immunohistochemical distribution of the wild-type epidermal growth factor
      receptor (EGFR), mutated forms of p53 protein and isocitrate dehydrogenase-1 (IDH
      1) and murine double protein 2 (MDM2). Immunostaining findings were correlated
      with clinical data and response to treatment (surgery, chemotherapy and
      radiotherapy). About 97% of the tumors were primary, most of them localized in
      the frontal lobe. Mean time free of clinical or symptomatic disease and free time
      of radiological disease were 7.56 and 7.14 months, respectively. We observed a
      significant positive correlation between expressions of p53 and MDM2, EGFR and
      MDM2. Clinical, radiological and overall survivals also showed a significant
      positive correlation. p53 staining and clinical survival showed a significant
      negative correlation. The current series provides clinical and histopathological
      data that contribute to knowledge on glioblastoma in Brazilians. 

PMID- 26200050
TI  - Neurodegenerative changes in the brainstem and olfactory bulb in people older
      than 50 years old: a descriptive study.
AB  - With the increase in life expectancy in Brazil, concerns have grown about the
      most prevalent diseases in elderly people. Among these diseases are
      neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Protein
      deposits related to the development of these diseases can pre-date the
      symptomatic phases by years. The tau protein is particularly interesting: it
      might be found in the brainstem and olfactory bulb long before it reaches the
      limbic cortex, at which point symptoms occur. Of the 14 brains collected in this
      study, the tau protein was found in the brainstems of 10 (71.42%) and in
      olfactory bulbs of 3 out 11. Of the 7 individuals who had a final diagnosis of
      Alzheimer's disease (AD), 6 presented tau deposits in some region of the
      brainstem. Our data support the idea of the presence of tau protein in the
      brainstem and olfactory bulb in the earliest stages of AD. 

PMID- 26200051
TI  - Chronic pain relief after the exposure of nitrous oxide during dental treatment:
      longitudinal retrospective study.
AB  - The objective was to investigate the effect of nitrous/oxygen in chronic pain.
      Seventy-seven chronic pain patients referred to dental treatment with conscious
      sedation with nitrous oxide/oxygen had their records included in this research.
      Data were collected regarding the location and intensity of pain by the visual
      analogue scale before and after the treatment. Statistical analysis was performed
      comparing pre- and post-treatment findings. It was observed a remarkable decrease
      in the prevalence of pain in this sample (only 18 patients still had chronic
      pain, p < 0.001) and in its intensity (p < 0.001). Patients that needed fewer
      sessions received higher proportions of nitrous oxide/oxygen. Nitrous oxide may
      be a tool to be used in the treatment of chronic pain, and future prospective
      studies are necessary to understand the underlying mechanisms and the effect of
      nitrous oxide/oxygen in patients according to the pain diagnosis and other
      characteristics. 

PMID- 26200052
TI  - Epidemiology of chronic pain in the office of a pain specialist neurologist.
AB  - OBJECTIVE: The objective of the present report was to describe the working
      experience of a pain specialist neurologist after concluding a medical residency
      program on neurology, area of concentration pain. METHOD: A retrospective study
      was conducted for one year in the office of a pain specialist neurologist.
      Patients older than 18 years with chronic pain according to the criteria of the
      International Association for the Study of Pain, were included. Demographic data,
      chronic pain data and the treatments instituted were investigated. RESULTS: A
      total of 241 medical records were reviewed, mean patient age was 52.4 years and
      79 (66.9%) were women, and the mean score on a numeric pain scale was 8.69. The
      diagnoses were headaches (74.6%), neuropathic pain (17%) and ostheomuscular pain
      (8.2%). We did not detect cancer pain. Patients received medication and
      procedures of anesthetic blockade. CONCLUSION: This data can guide new medical
      residency programs on Neurology, area of concentration pain, to plan activities
      and studies.

PMID- 26200053
TI  - Study of the use of analgesics by patients with headache at a specialized
      outpatient clinic (ACEF).
AB  - OBJECTIVE: To evaluate the use of analgesics in headache diagnosed in Outpatients
      Headache Clinic (ACEF), as well as his involvement in the activities of the
      patients. METHOD: 145 patients with headache seen at ACEF during the period
      August/July 2009/2010 underwent a questionnaire and interview with neurologist
      responsible for the final diagnosis according to ICHD-II. RESULTS: Relationship
      Women:Men 7:1. 1) Prevalence: Migraine without aura (52.4%), migraine with aura
      (12.4%), chronic migraine (15.2%) and medication overuse headache (MOH) (20%). 2)
      Analgesic drugs used: Compounds with Dipyrone (37%), Dipyrone (23%), Paracetamol
      (16%) compound with Paracetamol (6%), triptans (6%) and non steroidal anti
      inflammatory drugs (12%). There was a significant decrease in the duration of
      pain and less interference in the activities of the headache patients after the
      use of analgesics. CONCLUSION: Prevalence of MOH has been increasing in
      population level and specialized services. New studies emphasizing the MOH are
      needed to assist in the improvement of their diagnostic and therapeutic approach.

PMID- 26200054
TI  - Increased multiple sclerosis relapses related to lower prevalence of pain.
AB  - OBJECTIVE: The study aims to investigate the presence of pain amongst multiple
      sclerosis (MS) patients. METHOD: One hundred MS patients responded to
      questionnaires evaluating neuropathic and nociceptive pain, depression and
      anxiety. Statistical analysis was performed using the Mann-Whitney U, Chi-Square
      and two-tailed Fisher's exact tests and multivariate logistic regression.
      RESULTS: Women had a statistically higher prevalence of pain (p = 0.037), and
      chances of having pain after the age of 50 reduced. Women with pain had a
      statistically significant lower number of relapses (p = 0.003), restricting
      analysis to those patients with more than one relapse. After the second relapse,
      each relapse reduced the chance of having pain by 46%. Presence of pain was
      independent of Expanded Disability Status Scale (EDSS) anxiety, and depression.
      CONCLUSION: Our findings suggest a strong inverse association between relapses
      and pain indicating a possible protective role of focal inflammation in the
      control of pain.

PMID- 26200055
TI  - Relative luminosity in the plus maze upon the exploratory behaviour of female
      Wistar rats.
AB  - OBJECTIVE: This study evaluated the provision of two configuration of the
      Elevated Pluz-Maze (EPM) by analizing the exploratory behaviour of female Wistar
      rats in different phases of the estrous cycle in EPMs with different gradients of
      luminosity between the open and enclosed arms (O/E?Lux). METHODS: Female Wistar
      rats were treated with Midazolam (MDZ, 1.0 mg.kg-1) and were tested for their
      exploratory behaviour in either the EPM 10 O/E?Lux or EPM 96 O/E?Lux. RESULTS: A
      multiple regression analysis indicated that the O/E?Lux is negatively associated
      with the %Open arm entries and %Open arm time, suggesting that as O/E?Lux
      increases, the open arm exploration decreases. The estrous cycle phase did not
      influence the open-arm exploration in either EPM. MDZ- induced anxiolysis was
      detected in 96 O/E?Lux EPM in all phases of the EC. DISCUSSION: Results of this
      study suggest the importance of the O/E?Lux to establish the arm preference in
      the EPM, and to preserve the predictive validity of the EPM.

PMID- 26200056
TI  - Application of indocyanine green video angiography in surgical treatment of
      intracranial aneurysms.
AB  - Indocyanine green (ICG) video angiography has been used for several medical
      indications in the last decades. It allows a real time evaluation of vascular
      structures during the surgery. This study describes the surgical results of a
      senior vascular neurosurgeon. We retrospectively searched our database for all
      aneurysm cases treated with the aid of intraoperative ICG from 2009 to 2014. A
      total of 61 aneurysms in 56 patients were surgically clipped using intraoperative
      ICG. Clip reposition after ICG happened in 2 patients (3.2%). Generally, highly
      variable clip adjustment rates of 2%-38% following ICG have been reported since
      the introduction of this imaging technique. The application of ICG in vascular
      neurosurgery is still an emerging challenge. It is an adjunctive strategy which
      facilitates aneurismal evaluation and treatment in experienced hands.
      Nevertheless, a qualified vascular neurosurgeon is still the most important
      component of a high quality work. 

PMID- 26200057
TI  - Endoscopic combined "transseptal/transnasal" approach for pituitary adenoma:
      reconstruction of skull base using pedicled nasoseptal flap in 91 consecutive
      cases.
AB  - OBJECTIVE: The purpose of this study was to describe the endoscopic combined
      "transseptal/transnasal" approach with a pedicled nasoseptal flap for pituitary
      adenoma and skull base reconstruction, especially with respect to cerebrospinal
      fluid (CSF) fistula. METHOD: Ninety-one consecutive patients with pituitary
      adenomas were retrospectively reviewed. All patients underwent the endoscopic
      combined "transseptal/transnasal" approach by the single team including the
      otorhinolaryngologists and neurosurgeons. Postoperative complications related to
      the flap were analyzed. RESULTS: Intra- and postoperative CSF fistulae were
      observed in 36 (40%) and 4 (4.4%) patients, respectively. Among the 4 patients,
      lumbar drainage and bed rest healed the CSF fistula in 3 patients and reoperation
      for revision was necessary in one patient. Other flap-related complications
      included nasal bleeding in 3 patients (3.3%). CONCLUSION: The endoscopic combined
      "transseptal/transnasal" approach is most suitable for a two-surgeon technique
      and a pedicled nasoseptal flap is a reliable technique for preventing
      postoperative CSF fistula in pituitary surgery.

PMID- 26200058
TI  - Neuroinflammation in the pathophysiology of Parkinson's disease and therapeutic
      evidence of anti-inflammatory drugs.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease
      affecting approximately 1.6% of the population over 60 years old. The cardinal
      motor symptoms are the result of progressive degeneration of substantia nigra
      pars compacta dopaminergic neurons which are involved in the fine motor control.
      Currently, there is no cure for this pathology and the cause of the
      neurodegeneration remains unknown. Several studies suggest the involvement of
      neuroinflammation in the pathophysiology of PD as well as a protective effect of
      anti-inflammatory drugs both in animal models and epidemiological studies,
      although there are controversial reports. In this review, we address evidences of
      involvement of inflammatory process and possible therapeutic usefulness of anti
      inflammatory drugs in PD. 

PMID- 26200059
TI  - Cerebrospinal fluid analysis in the HIV infection and compartmentalization of HIV
      in the central nervous system.
AB  - The nervous system plays an important role in HIV infection. The purpose of this
      review is to discuss the indications for cerebrospinal fluid (CSF) analysis in
      HIV infection in clinical practice. CSF analysis in HIV infection is indicated
      for the diagnosis of opportunistic infections and co-infections, diagnosis of
      meningitis caused by HIV, quantification of HIV viral load, and analysis of CNS
      HIV compartmentalization. Although several CSF biomarkers have been investigated,
      none are clinically applicable. The capacity of HIV to generate genetic
      diversity, in association with the constitutional characteristics of the CNS,
      facilitates the generation of HIV quasispecies in the CNS that are distinct from
      HIV in the systemic circulation. CSF analysis has a well-defined and valuable
      role in the diagnosis of CNS infections in HIV/AIDS patients. Further research is
      necessary to establish a clinically applicable biomarker for the diagnosis of HIV
      associated neurocognitive disorders. 

PMID- 26200060
TI  - In the land of giants: the legacy of Jose Dantas de Souza Leite.
AB  - The authors describe the extraordinary contribution to science made by Jose
      Dantas de Souza Leite, who graduated from the Bahia School of Medicine and
      trained in Prof. Charcot's Neurology Service under the supervision of Charcot's
      most able pupil, Dr. Pierre Marie. Souza Leite presented his doctoral thesis on
      acromegaly, in Paris in 1890, and in the following year both him and Pierre Marie
      published a book on the subject, "Essays on Acromegaly". This exceptional work
      established Souza Leite internationally as an important researcher, and the first
      Brazilian physician to contribute to the development of neuroendocrinology in an
      innovative way. 

PMID- 26200061
TI  - Neuroimaging features of progressive ataxia and palatal tremor.

PMID- 26200062
TI  - Trigeminal nerve thickening in chronic inflammatory demyelinating polyneuropathy.

PMID- 26200063
TI  - Primary meningeal melanoma with cerebrospinal fluid dissemination mimicking
      neurofibromatosis type 2.

PMID- 26200064
TI  - Ataxia telangiectasia.

PMID- 26200065
TI  - Hydrophobic benzyl amines as supports for liquid-phase C-terminal amidated
      peptide synthesis: application to the preparation of ABT-510.
AB  - C-terminal amidation is one of the most common modification of peptides and
      frequently found in bioactive peptides. However, the C-terminal modification must
      be creative, because current chemical synthetic techniques of peptides are
      dominated by the use of C-terminal protecting supports. Therefore, it must be
      carried out after the removal of such supports, complicating reaction work-up and
      product isolation. In this context, hydrophobic benzyl amines were successfully
      added to the growing toolbox of soluble tag-assisted liquid-phase peptide
      synthesis as supports, leading to the total synthesis of ABT-510 (2). Although an
      ethyl amide-forming type was used in the present work, different types of
      hydrophobic benzyl amines could also be simply designed and prepared through
      versatile reductive aminations in one step. The standard acidic treatment used in
      the final deprotection step for peptide synthesis gave the desired C-terminal
      secondary amidated peptide with no epimerization.

PMID- 26200066
TI  - Imide-Modified Dinaphtho[1,2-b:2',1'-d]thiophene and Dinaphtho[1,2-b:2',1'
      d]thiophene 13,13-Dioxide: Synthesis and Optoelectronic Properties.
AB  - Dinaphthothiophene has been reported as a promising p-type semiconductor. The
      development of high-performance n-type semiconductors is highly desirable. The
      introduction of an imide group into polycyclic aromatic hydrocarbons can lower
      their LUMO levels to meet the basic requirement of n-type organic semiconductor
      materials. In this work, we have synthesized four imide-modified
      dinaphthothiophenes and dinaphthothiophenedioxides. Their optoelectronic
      properties have been investigated. Their low-lying LUMO levels make them
      potential n-type semiconductor candidates. 

PMID- 26200067
TI  - Hybridization of Cd0.2Zn0.8S with g-C3N4 nanosheets: a visible-light-driven
      photocatalyst for H2 evolution from water and degradation of organic pollutants.
AB  - Novel visible-light-driven Cd0.2Zn0.8S/g-C3N4 inorganic-organic composite
      photocatalysts were synthesized by a facile hydrothermal method. The prepared
      Cd0.2Zn0.8S/g-C3N4 composites were characterized by X-ray diffraction (XRD), X
      ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT
      IR), transmission electron microscopy (TEM), high-resolution transmission
      electron microscopy (HRTEM), ultraviolet-visible diffuse reflection spectroscopy
      (DRS), photoluminescence (PL) spectroscopy and photoelectrochemical (PEC)
      experiments. Under visible-light irradiation, Cd0.2Zn0.8S/g-C3N4 photocatalysts
      displayed a higher photocatalytic activity than pure g-C3N4 and Cd0.2Zn0.8S for
      hydrogen evolution and degradation of pollutants, and the optimal g-C3N4 content
      was 20 wt%. The optimal composite showed a hydrogen evolution rate of 208.0 MUmol
      h(-1). The enhancement of the photocatalytic activity should be attributed to the
      well-matched band structure and intimate contact interfaces between Cd0.2Zn0.8S
      and g-C3N4, which lead to the effective transfer and separation of the
      photogenerated charge carriers. Furthermore, the Cd0.2Zn0.8S/g-C3N4
      photocatalysts showed excellent stability during photocatalytic hydrogen
      evolution and degradation of pollutants. 

PMID- 26200071
TI  - Chronic pain: it's different for girls.

PMID- 26200069
TI  - Incidence- Versus Prevalence-Based Measures of Inappropriate Prescribing in the
      Veterans Health Administration.
AB  - OBJECTIVES: To describe variations in potentially inappropriate prescribing (PIP)
      and characterize the extent to which switching to an incidence-based indicator
      would affect health system quality rankings. DESIGN: Observational study.
      SETTING: Veterans Health Administration in 2011. PARTICIPANTS: Older adults
      receiving outpatient primary care. MEASUREMENTS: PIP was defined according to the
      National Committee for Quality Assurance High-Risk Medications in the Elderly
      list. Ranks were separately assigned for prevalent and incident PIP at the
      regional, network, and healthcare system levels. RESULTS: National PIP prevalence
      was 12.3% (167,766/1,360,251), and incidence was 5.8% (78,604/1,360,251). PIP
      prevalence ranged from 3.5% to 33.1% across healthcare systems (interquartile
      range (IQR) = 9.2-15.5%). PIP incidence ranged from 1.2% to 14.9% (IQR = 4.1
      7.2%). Rank order in PIP prevalence and incidence was correlated (Spearman
      correlation; rho = 0.934, P < .001), although substantial changes in ranks were
      seen for some healthcare systems, with seven of 139 (5.0%) systems shifting more
      than 30 rank positions and 21 (15.1%) systems shifting 16 to 30 positions.
      CONCLUSION: Prevalence- and incidence-based indicators of prescribing quality
      were strongly correlated. Transitioning to incidence-based indicators would not
      produce an initial disruption in quality rankings for most healthcare systems and
      might yield more-salient measures for tracking healthcare quality.

PMID- 26200072
TI  - A patch that fixes insulin delivery.

PMID- 26200068
TI  - Age at First Exposure to Football Is Associated with Altered Corpus Callosum
      White Matter Microstructure in Former Professional Football Players.
AB  - Youth football players may incur hundreds of repetitive head impacts (RHI) in one
      season. Our recent research suggests that exposure to RHI during a critical
      neurodevelopmental period prior to age 12 may lead to greater later-life mood,
      behavioral, and cognitive impairments. Here, we examine the relationship between
      age of first exposure (AFE) to RHI through tackle football and later-life corpus
      callosum (CC) microstructure using magnetic resonance diffusion tensor imaging
      (DTI). Forty retired National Football League (NFL) players, ages 40-65, were
      matched by age and divided into two groups based on their AFE to tackle football:
      before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla
      Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and
      seeded using deterministic tractography. Dependent measures were fractional
      anisotropy (FA), trace, axial diffusivity, and radial diffusivity. Results showed
      that former NFL players in the AFE <12 group had significantly lower FA in
      anterior three CC regions and higher radial diffusivity in the most anterior CC
      region than those in the AFE >=12 group. This is the first study to find a
      relationship between AFE to RHI and later-life CC microstructure. These results
      suggest that incurring RHI during critical periods of CC development may disrupt
      neurodevelopmental processes, including myelination, resulting in altered CC
      microstructure.

PMID- 26200074
TI  - Probing the puzzle of persistent pests.

PMID- 26200075
TI  - Hitting a nerve to ease asthma.

PMID- 26200077
TI  - A bird in the lab.

PMID- 26200078
TI  - Add Bryant to the protocol.

PMID- 26200079
TI  - Protocol with an unlisted collaborator.

PMID- 26200080
TI  - Safety is the main concern.

PMID- 26200081
TI  - Not in the protocol, not approved.

PMID- 26200082
TI  - Refining analgesia strategies using lasers.
AB  - Sound programs for the humane care and use of animals within research facilities
      incorporate experimental refinements such as multimodal approaches for pain
      management. These approaches can include non-traditional strategies along with
      more established ones. The use of lasers for pain relief is growing in popularity
      among companion animal veterinary practitioners and technologists. Therefore, its
      application in the research sector warrants closer consideration. 

PMID- 26200084
TI  - Effects of different blood collection methods on indicators of welfare in mice.
AB  - Blood collection is a common experimental procedure for which there are many
      different methods, each with its own advantages and disadvantages. Researchers
      should use methods that minimize pain, suffering, distress and lasting harm to
      animals while meeting study requirements. The authors evaluated stress, activity
      and tissue damage in BALB/cO1aHsd mice after collecting blood using one of six
      methods: retrobulbar bleeding with thin or thick capillaries, tail vein bleeding,
      saphenous vein bleeding, facial vein bleeding or jugular vein bleeding. The
      authors compared in-cage activity, corticosterone concentration and performance
      in open-field tests between treatment groups and collected histologic samples at
      1 h, 3 d and 14 d after bleeding. Mice that underwent retrobulbar bleeding with a
      thick capillary had a smaller change in corticosterone concentration and higher
      in-cage activity immediately after blood collection, whereas mice that underwent
      jugular vein bleeding had a greater change in corticosterone concentration and
      lower in-cage activity and open-field activity. Mice that underwent saphenous
      vein bleeding had a high incidence of histological change at 1 h, 3 d and 14 d
      after blood collection, but few indicators of histological change were present in
      other groups at 14 d after blood collection. These results suggest that, when
      collecting a small volume of blood, retrobulbar bleeding with a thick capillary
      and without anesthesia causes the least stress in mice, whereas jugular vein
      bleeding and facial vein bleeding cause the most stress and saphenous vein
      bleeding causes the most lasting damage in mice. 

PMID- 26200085
TI  - Effects of pelleted or powdered diets containing soy protein or sodium caseinate
      on lipid concentrations and bile acid excretion in golden Syrian hamsters.
AB  - Custom diets are a convenient vector for oral administration of test articles,
      but the processing and physical form of a diet can affect its nutritional
      properties and how it is consumed. Here, the authors evaluated the feeding
      behavior and physiology of golden Syrian hamsters fed diets of either soy or
      caseinate protein in pelleted or powdered forms for 28 d to determine whether
      dietary processing and form mediates the physiological effects of dietary
      proteins. The authors compared body weight, food consumption, serum cholesterol
      concentration, serum triglyceride concentration, fecal weight and fecal excretion
      of bile acids between treatment groups. Hamsters fed powdered diets showed higher
      food consumption than hamsters fed pelleted diets, regardless of protein source.
      Hamsters fed soy pelleted diets showed lower serum cholesterol concentration and
      higher fecal excretion of bile acid than hamsters fed caseinate pelleted diets,
      and serum cholesterol concentration correlated strongly with fecal excretion of
      bile acid. This correlation suggests that the physiological effects of soy
      protein on cholesterol and excretion of bile acid might be related or similarly
      mediated through diet. The differences observed between hamsters on different
      diets indicate that dietary form can influence both feeding behavior and the
      physiological effects of a diet in hamsters. 

PMID- 26200086
TI  - Developing an online orientation resource for users of institutional animal
      housing facilities.
AB  - Institutions can share information and orientation materials easily and
      effectively using modern media and communications technology. For this reason the
      Office of Animal Care and Use at the University of Georgia developed an online
      orientation resource for users of its animal housing facilities. Here the authors
      describe the resource and the planning and project management that accompanied
      its development. The authors explain the rationale behind each of their decisions
      and describe select organizational methods that contributed to the success of the
      project. They describe their own experience, in the context of their
      institutional circumstances, for the benefit of other institutions that might
      consider developing a similar resource. 

PMID- 26200087
TI  - Learning the ABCs because of an SFI.

PMID- 26200088
TI  - Either open up, or give up.

PMID- 26200089
TI  - Teaching and learning in a Xenopus research lab.

PMID- 26200090
TI  - MRI-determined lumbar muscle morphometry in man and sheep: potential
      biomechanical implications for ovine model to human spine translation.
AB  - The sheep is a commonly used animal model for human lumbar spine surgery, but
      only in vitro investigations comparing the human and ovine spine exist. Spinal
      musculature has previously not been compared between man and sheep. This
      additional knowledge could further indicate to what extent these species are
      biomechanically similar. Therefore, the purpose of the study was to investigate
      spinal muscle morphometric properties using magnetic resonance imaging (MRI) in
      different age groups of healthy human participants and sheep in vivo. Healthy
      human participants (n = 24) and sheep (n = 17) of different age groups underwent
      T1-weighted MRI of the lumbar spine. Regions of interest of the muscles erector
      spinae (ES), multifidus (M) and psoas (PS) were identified. The ratio of flexor
      to extensor volume, ratio of M to ES volume, and muscle fat relative to an area
      of intermuscular fat were calculated. Sheep M to ES ratio was significantly
      smaller than in the human participants (sheep 0.16 +/- 0.02; human 0.37 +/- 0.05;
      P < 0.001), although flexor to extensor ratio was not significantly different
      between species (human 0.39 +/- 0.08; sheep 0.43 +/- 0.05; P = 0.06). Age did not
      influence any muscle ratio outcome. Sheep had significantly greater extensor
      muscle fat compared with the human participants (M left human 40.64%, sheep
      53.81%; M right human 39.17%, sheep 51.33%; ES left human 40.86%, sheep 51.29%;
      ES right human 35.93%, sheep 44.38%; all median values; all P < 0.001), although
      PS did not show any significant between-species differences (PS left human
      36.89%, sheep 33.67%; PS right human 32.78%, sheep 30.09%; P < 0.05). The
      apparent differences in the size and shape of sheep and human lumbar spine
      muscles may indicate dissimilar biomechanical and functional demands, which is an
      important consideration when translating to human surgical models.

PMID- 26200092
TI  - The Selective Estrogen Receptor Modulator Raloxifene Regulates Arginine
      Vasopressin Gene Expression in Human Female Neuroblastoma Cells Through G Protein
      Coupled Estrogen Receptor and ERK Signaling.
AB  - The selective estrogen receptor modulator raloxifene reduces blood pressure in
      hypertensive postmenopausal women. In the present study we have explored whether
      raloxifene regulates gene expression of arginine vasopressin (AVP), which is
      involved in the pathogenesis of hypertension. The effect of raloxifene was
      assessed in human female SH-SY5Y neuroblastoma cells, which have been recently
      identified as a suitable cellular model to study the estrogenic regulation of
      AVP. Raloxifene, within a concentration ranging from 10(-10) M to 10(-6) M,
      decreased the mRNA levels of AVP in SH-SY5Y cells with maximal effect at 10(-7)
      M. This effect of raloxifene was imitated by an agonist (+/-)-1-[(3aR*,4S*,9bS*)
      4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8
      yl]-ethanone of G protein-coupled estrogen receptor-1 (GPER) and blocked by an
      antagonist (3aS*,4R*,9bR*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H
      cyclopenta[c]quinoline of GPER and by GPER silencing. Raloxifene induced a time
      dependent increase in the level of phosphorylated ERK1 and ERK2, by a mechanism
      blocked by the GPER antagonist. The treatment of SH-SY5Y cells with either a
      MAPK/ERK kinase 1/2-specific inhibitor (1,4-diamino-2, 3-dicyano-1,4-bis(2
      aminophenylthio)butadine) or a protein kinase C inhibitor (sotrastaurin) blocked
      the effects of raloxifene on the phosphorylation of ERK1/2 and the regulation of
      AVP mRNA levels. These results reveal a mechanism mediating the regulation of AVP
      expression by raloxifene, involving the activation of GPER, which in turn
      activates protein kinase C, MAPK/ERK kinase, and ERK. The regulation of AVP by
      raloxifene and GPER may have implications for the treatment of blood
      hypertension(.).

PMID- 26200094
TI  - Limb and back muscle activity adaptations to tripedal locomotion in dogs.
AB  - Alterations in muscle recruitment are key to the functional plasticity of the
      mammalian locomotor system. One particularly challenging situation quadrupeds may
      face is when the functionality of a limb is reduced or lost. To better understand
      how mammals manage in such situations and which muscular adaptations they exhibit
      when locomoting on three legs, we recorded the activity patterns of two limb and
      one back extensor muscle in nine dogs using surface electromyography. We compared
      the timing and the level of recruitment before and after the loss of a hindlimb
      was simulated. Both the intensity and the timing of the activity changed
      significantly in the m. vastus lateralis of the remaining hindlimb, consistent
      with this limb bearing a greater proportion of the body weight as well as with
      previously reported kinematic changes. In accordance with the greater body weight
      supported by the forelimbs, the m. triceps brachii showed first and foremost an
      increased level of excitation. The very asymmetrical changes in the timing and
      the level of activity in the m. longissimus dorsi reflects the highly
      asymmetrical functional requirements imposed on the trunk and the pelvis when one
      hindlimb is no longer involved in the production of locomotor work while the
      other hindlimb partially compensates the loss. Integration of our
      electromyographical findings with kinetic and kinematic results illustrates that
      dogs exhibited a well-coordinated response to the functional requirements of
      tripedalism and underlines the importance of moment-to-moment modulation in
      muscular recruitment for the functional plasticity of the mammalian locomotor
      system.

PMID- 26200093
TI  - Tctex1d2 Is a Negative Regulator of GLUT4 Translocation and Glucose Uptake.
AB  - Tctex1d2 (Tctex1 domain containing 2) is an open reading frame that encodes for a
      functionally unknown protein that contains a Tctex1 domain found in dynein light
      chain family members. Examination of gene expression during adipogenesis
      demonstrated a marked increase in Tctex1d2 protein expression that was
      essentially undetectable in preadipocytes and markedly induced during 3T3-L1
      adipocyte differentiation. Tctex1d2 overexpression significantly inhibited
      insulin-stimulated glucose transporter 4 (GLUT4) translocation and 2-deoxyglucose
      uptake. In contrast, Tctex1d2 knockdown significantly increased insulin
      stimulated GLUT4 translocation and 2-deoxyglucose uptake. However, acute insulin
      stimulation (up to 30 min) in 3T3-L1 adipocytes with overexpression or knockdown
      of Tctex1d2 had no effect on Akt phosphorylation, a critical signal transduction
      target required for GLUT4 translocation. Although overexpression of Tctex1d2 had
      no significant effect on GLUT4 internalization, Tctex1d2 was found to associate
      with syntaxin 4 in an insulin-dependent manner and inhibit Doc2b binding to
      syntaxin 4. In addition, glucose-dependent insulinotropic polypeptide rescued the
      Tctex1d2 inhibition of insulin-stimulated GLUT4 translocation by suppressing the
      Tctex1d2-syntaxin 4 interaction and increasing Doc2b-Synatxin4 interactions.
      Taking these results together, we hypothesized that Tctex1d2 is a novel syntaxin
      4 binding protein that functions as a negative regulator of GLUT4 plasma membrane
      translocation through inhibition of the Doc2b-syntaxin 4 interaction.

PMID- 26200095
TI  - Deletional and regulatory mechanisms coalesce to drive transplantation tolerance
      through mixed chimerism.
AB  - Establishing donor-specific immunological tolerance could improve long-term
      outcome by obviating the need for immunosuppressive drug therapy, which is
      currently required to control alloreactivity after organ transplantation. Mixed
      chimerism is defined as the engraftment of donor hematopoietic stem cells in the
      recipient, leading to viable coexistence of both donor and recipient leukocytes.
      In numerous experimental models, cotransplantation of donor bone marrow (BM) into
      preconditioned (e.g., through irradiation or cytotoxic drugs) recipients leads to
      transplantation tolerance through (mixed) chimerism. Mixed chimerism offers
      immunological advantages for clinical translation; pilot trials have established
      proof of concept by deliberately inducing tolerance in humans. Widespread
      clinical application is prevented, however, by the harsh preconditioning
      currently necessary for permitting BM engraftment. Recently, the immunological
      mechanisms inducing and maintaining tolerance in experimental mixed chimerism
      have been defined, revealing a more prominent role for regulation than
      historically assumed. The evidence from murine models suggests that both
      deletional and regulatory mechanisms are critical in promoting complete
      tolerance, encompassing also the minor histocompatibility antigens. Here, we
      review the current understanding of tolerance through mixed chimerism and provide
      an outlook on how to realize widespread clinical translation based on mechanistic
      insights gained from chimerism protocols, including cell therapy with polyclonal
      regulatory T cells.

PMID- 26200096
TI  - Carbyne: The Molecular Approach.
AB  - For the last 60+ years, the synthesis and study of cumulenes and polyynes have
      been the focus of a small, but dedicated, group of researchers. Many of the
      remarkable electronic, optical, and structural properties of cumulenes and
      polyynes had already been identified in the earliest reports. The molecular
      lengths achievable by the initial syntheses were, unfortunately, somewhat limited
      by synthetic methods available. For the past 15 years, we have worked toward
      expanding on the synthesis of cumulenes and polyynes through the development of
      new methods and stabilization motifs. As new compounds have become available,
      homologous series of cumulenes and polyynes have then been examined as a function
      of molecular length. While we are not yet there, we would like to eventually
      provide a general description of the sp-carbon allotrope carbyne, and this
      account presents some of our efforts toward this goal. 

PMID- 26200097
TI  - Tumor Budding in Colorectal Carcinoma: Confirmation of Prognostic Significance
      and Histologic Cutoff in a Population-based Cohort.
AB  - Tumor budding in colorectal carcinoma has been associated with poor outcome in
      multiple studies, but the absence of an established histologic cutoff for "high"
      tumor budding, heterogeneity in study populations, and varying methods for
      assessing tumor budding have hindered widespread incorporation of this parameter
      in clinical reports. We used an established scoring system in a population-based
      cohort to determine a histologic cutoff for "high" tumor budding and confirm its
      prognostic significance. We retrieved hematoxylin and eosin-stained sections from
      553 incident colorectal carcinoma cases. Each case was previously characterized
      for select molecular alterations and survival data. Interobserver agreement was
      assessed between 2 gastrointestinal pathologists and a group of 4 general
      surgical pathologists. High budding (>= 10 tumor buds in a *20 objective field)
      was present in 32% of cases, low budding in 46%, and no budding in 22%. High
      tumor budding was associated with advanced pathologic stage (P < 0.001),
      microsatellite stability (P = 0.005), KRAS mutation (P = 0.010), and on
      multivariate analysis with a > 2 times risk of cancer-specific death (hazard
      ratio = 2.57 [1.27, 5.19]). After multivariate adjustment, by penalized smoothing
      splines, we found increasing tumor bud counts from 5 upward to be associated with
      an increasingly shortened cancer-specific survival. By this method, a tumor bud
      count of 10 corresponded to approximately 2.5 times risk of cancer-specific
      death. The interobserver agreement was good with weighted kappa of 0.70 for 2
      gastrointestinal pathologists over 121 random cases and 0.72 between all 6
      pathologists for 20 random cases. Using an established method to assess budding
      on routine histologic stains, we have shown that a cutoff of 10 for high tumor
      budding is independently associated with a significantly worse prognosis. The
      reproducibility data provide support for the routine widespread implementation of
      tumor budding in clinical reports.

PMID- 26200098
TI  - Superior Mesenteric Artery Margin of Posttherapy Pancreaticoduodenectomy and
      Prognosis in Patients With Pancreatic Ductal Adenocarcinoma.
AB  - Negative-margin resection is crucial to favorable prognosis in patients with
      pancreatic ductal adenocarcinoma. However, the definition of a negative superior
      mesenteric artery margin (SMAM) varies. The College of American Pathologists
      defines positive SMAM as the presence of tumor cells at the margin, whereas the
      European protocol is based on a 1 mm clearance. In this study, we examined the
      prognostic significance of the SMAM distance in 411 consecutive pancreatic ductal
      adenocarcinoma patients who completed neoadjuvant therapy and
      pancreaticoduodenectomy. Per College of American Pathologists criteria, 32 (7.8%)
      had positive margins, and 379 (92.2%) had negative margins. Among margin-negative
      group, SMAM was <= 1, 1.0 to 5.0, and >5.0 mm in 66, 145, and 168 patients,
      respectively. There was no difference in either disease-free survival (DFS) or
      overall survival (OS) between the positive-margin group and SMAM <= 1 mm (P >
      0.05). However, patients with SMAM 1.0 to 5.0 mm had better OS than those with
      positive margins or SMAM <= 1 mm (P = 0.02). Patients with SMAM > 5.0 mm had
      better DFS and OS than those with SMAM 1.0 to 5.0 mm and those with positive
      margins or SMAM <= 1 mm (P < 0.01). By multivariate analysis, the SMAM distance,
      tumor differentiation, lymph node metastasis, and histopathologic tumor response
      grade were independent prognostic factors for both DFS and OS. SMAM distance
      correlated with lower ypT and AJCC stages, smaller tumor size, better
      histopathologic tumor response grade, fewer lymph node metastases, and
      recurrences (P < 0.05). Thus our results strongly support use of SMAM > 1 mm for
      R0 resection in posttherapy pancreaticoduodenectomy specimens.

PMID- 26200099
TI  - Microcystic Stromal Tumor: A Distinctive Ovarian Sex Cord-Stromal Neoplasm
      Characterized by FOXL2, SF-1, WT-1, Cyclin D1, and beta-catenin Nuclear
      Expression and CTNNB1 Mutations.
AB  - Since our first description of the microcystic stromal tumor (MST) of the ovary,
      a rare and distinctive neoplasm with a definitional, usually striking microcystic
      pattern and a CD10+/vimentin+/inhibin-/calretinin- immunophenotype, 3 examples
      with beta-catenin nuclear localization, and CTNNB1 mutation have been reported.
      We undertook a detailed immunohistochemical study and molecular analysis of
      CTNNB1 and FOXL2 of 15 cases of MST to further characterize this neoplasm and
      establish its histogenesis. Diffuse nuclear staining for FOXL2, WT-1, cyclin D1,
      and beta-catenin was present in all tumors tested, and 12/15 were positive for
      steroidogenic factor-1 (SF-1). Heterozygous missense point mutations in exon 3 of
      CTNNB1 were detected in 8 of 14 cases, resulting in amino acid changes at codons
      32, 34, 35, and 37. There was no correlation between CTNNB1 exon 3 mutation
      status and tumor immunophenotype. All 14 cases tested showed wild-type FOXL2. Our
      study establishes that MST of the ovary exhibits a characteristic FOXL2/SF-1/WT
      1/cyclin D1/nuclear beta-catenin-positive immunohistochemical profile, which may
      be useful in diagnosis and in the exclusion of histologic mimics. The presence of
      diffuse nuclear FOXL2 and WT-1 immunostaining in all cases and SF-1 in most
      supports the classification of MST within the sex cord-stromal category. Aberrant
      nuclear beta-catenin expression, detected in all MSTs, appears to be the result
      of stabilizing CTNNB1 mutations in 57% of cases, providing further evidence that
      dysregulation of the Wnt/B-catenin pathway is involved in the tumorigenesis of
      MST and may involve activation of beta-catenin with upregulation of cyclin D1.

PMID- 26200100
TI  - Cystic Neutrophilic Granulomatous Mastitis: Further Characterization of a
      Distinctive Histopathologic Entity Not Always Demonstrably Attributable to
      Corynebacterium Infection.
AB  - Granulomatous lobular mastitis (GLM) is an uncommon condition that typically
      occurs in parous, reproductive-aged women and can simulate malignancy on the
      basis of clinical and imaging features. A distinctive histologic pattern termed
      cystic neutrophilic granulomatous mastitis (CNGM) is seen in some cases of GLM
      and has been associated with Corynebacterium infection. We sought to further
      characterize the clinical, imaging, and histopathologic features of CNGM by
      studying 12 cases and attempted to establish the relationship of this disease
      with Corynebacterium infection. Patients were women ranging in age from 25 to 49
      years (median: 34 y), and all presented with a palpable mass that was painful in
      half of the cases. In 2 of 9 cases, imaging was highly suspicious for malignancy
      (BI-RADS 5). CNGM was characterized by lobulocentric granulomas with mixed
      inflammation and clear vacuoles lined by neutrophils within granulomas. Gram
      positive bacilli were identified in 5/12 cases. In 4 patients, the disease
      process worsened after the diagnostic core biopsy, with the development of a
      draining sinus in 2 cases. No growth of bacteria was seen in any microbial
      cultures. No bacterial DNA was identified by 16S rDNA polymerase chain reaction
      for 1 case that showed gram-positive bacilli on histology. Patients were treated
      with variable combinations of surgery, antibiotics, and steroids. The time to
      significant resolution of symptoms ranged from 2 weeks to 6 months. Similar to
      other forms of GLM, CNGM can mimic malignancy clinically and on imaging. When
      encountered in a needle core biopsy sample, recognition of the characteristic
      histologic pattern and its possible association with Corynebacterium infection
      can help guide treatment. 

PMID- 26200101
TI  - Nitric Oxide Catalysis of Diazene E/Z Isomerization.
AB  - Nitric oxide is an efficient catalyst for the cis-trans (E/Z) isomerization of
      diazenes. We compare the effect of room temperature solutions bearing low
      concentrations of nitric oxide, nitrogen dioxide, or oxygen on the rate of cis
      trans isomerization, CTI, of the alkene bond in stilbene and on the azo double
      bond in azobenzene, as well as in four azo derivatives as measured by UV-vis
      spectroscopy. These rate enhancements can be as large as 3 orders of magnitude
      for azobenzene in solution. A mechanism is proposed where catalysis is promoted
      by the interaction of the nitric oxide with the diazene nitrogen lone pairs.
      Density functional theory, B3LYP/6-311++g** suggests that the binding of NO to
      the diazene should be weak and reversible but that its NO adduct has an E/Z
      isomerization barrier of 7.5 kcal/mol. 

PMID- 26200102
TI  - Theoretical Investigation of the Reaction Paths of the Aluminum Cluster Cation
      with Water Molecule in the Gas Phase: A Facile Route for Dihydrogen Release.
AB  - The gas-phase reaction of the Al6(+) cation with a water molecule is investigated
      computationally by coupled cluster and density functional theories. Several low
      energy paths of the mechanism for dihydrogen production from H2O by the
      positively charged aluminum cluster are identified. This reaction involves the
      initial formation of the association complex, exothermic by 25 kcal/mol, followed
      by the water dissociation and H2 elimination major steps, yielding the Al6O(+)
      product oxide with either the nonplanar or planar structure. The H2O dissociation
      on Al6(+) is the rate-determining step. Of the paths probed, the one kinetically
      most preferred leads from the O-H bond dissociation transition state lying below
      the separated reactants to the immediate HAl6OH(+) intermediate of the "open"
      type and involves further the more compact intermediate from which H2 is
      eliminated. The other reaction paths explored involve the activation enthalpy (at
      0 K) for the rate-determining step of less than 2 kcal/mol relative to the Al6(+)
      + H2O. Natural population analysis based charges indicate that forming of H2
      along the elimination coordinate is facilitated by the interaction of the
      hydridic and protic hydrogens. For the kinetically most favorable route detected,
      the coupled cluster singles and doubles with perturbative triples (CCSD(T))
      relative energies calculated with the unrestricted and restricted HF references
      are in a good agreement. This investigation is relevant specifically to the
      recent mass spectrometric study of the reactivity of Aln(+) with water by Arakawa
      et al., and it provides a mechanistic insight into the formation of the observed
      AlnO(+) product oxide with n = 6. 

PMID- 26200103
TI  - Mono- and di-cationic hydrido boron compounds.
AB  - Bronsted acid HNTf2 (Tf = SO2CF3) mediated dehydrogenative hydride abstraction
      from (L(1))BH3 () and (L(2))BH3 () (L(1) = IPrCH2 = 1,3-(2,6-di
      isopropylphenyl)imidazol-2-methylidene (); L(2) = SIPrCH2 = 1,3-(2,6-di
      isopropylphenyl)imidazolidin-2-methylidiene ()) affords thermally stable hydride
      bridged mono-cationic hydrido boron compounds [{(L(1))BH2}2(MU-H)](NTf2) () and
      [{(L(2))BH2}2(MU-H)](NTf2) (). Furthermore, hydride abstraction yields di
      cationic hydrido boron compounds [{(L(1))BH}2(MU-H)2](NTf2)2 () and
      [{(L(2))BH}2(MU-H)2](NTf2)2 (). Unique cationic boron compounds with CH2BH2(MU
      H)BH2CH2 ( and ) and CH2BH(MU-H)2BHCH2 ( and ) moieties feature a 3c-2e bond and
      have been fully characterized. Interesting electronic and structural features of
      compounds are analysed using spectroscopic, crystallographic, and computational
      methods. 

PMID- 26200104
TI  - The fragile Y hypothesis: Y chromosome aneuploidy as a selective pressure in sex
      chromosome and meiotic mechanism evolution.
AB  - Loss of the Y-chromosome is a common feature of species with chromosomal sex
      determination. However, our understanding of why some lineages frequently lose Y
      chromosomes while others do not is limited. The fragile Y hypothesis proposes
      that in species with chiasmatic meiosis the rate of Y-chromosome aneuploidy and
      the size of the recombining region have a negative correlation. The fragile Y
      hypothesis provides a number of novel insights not possible under traditional
      models. Specifically, increased rates of Y aneuploidy may impose positive
      selection for (i) gene movement off the Y; (ii) translocations and fusions which
      expand the recombining region; and (iii) alternative meiotic segregation
      mechanisms (achiasmatic or asynaptic). These insights as well as existing
      evidence for the frequency of Y-chromosome aneuploidy raise doubt about the
      prospects for long-term retention of the human Y-chromosome despite recent
      evidence for stable gene content in older non-recombining regions. 

PMID- 26200105
TI  - Blood Vessel Maturation by Disintegrin in Oxygen-Induced Retinopathy.
AB  - PURPOSE: Although Arg-Gly-Asp (RGD) motif-containing disintegrins are associated
      with integrin inhibition and the activation of various biological processes,
      little is known about the role of RGD motif-containing disintegrin in vascular
      development and remodeling. We therefore investigated the role of RGD-containing
      disintegrin in vascular remodeling in oxygen-induced retinopathy (OIR) mouse
      model. MATERIALS AND METHODS: EGT022, an RGD-containing disintegrin originated
      from human a disintegrin and metalloproteinase 15 (ADAM15), was used to
      investigate the role of the disintegrin in vascular development in OIR mouse
      model. To analyze the functional effects of EGT022 on retinal vascular
      development, the immunohistochemistry on mouse retinas after fluorescein
      isothiocyanate (FITC) perfusion was conducted and the vessel integrity was
      examined using modified Mile's permeability assay. RESULTS: EGT022 was able to
      reduce overall retinopathy scores by 75%, indicating its efficacy in retinal
      microvessel maturation stimulation. Pericyte coverage was greatly stimulated by
      EGT022 treatment in OIR mouse model. EGT022 was also effective to significantly
      improve blood vessel integrity. CONCLUSIONS: RGD-containing disintegrin EGT022
      stimulated vascular maturation in OIR mouse model. Experimental results suggest
      that EGT022 is useful for treatments to improve ischemia in nonproliferative
      diabetic retinopathy (NPDR), the early stage of diabetic retinopathy.

PMID- 26200106
TI  - New Series of Dinuclear Ruthenium(II) Complexes Synthesized Using
      Photoisomerization for Efficient Water Oxidation Catalysis.
AB  - A new series of proximal,proximal-[Ru2(tpy)2(L)XY](n+) (p,p-Ru2XY, tpy =
      2,2':6',2"-terpyridine, L = 5-phenyl-2,8-di(2-pyridyl)-1,9,10-anthyridine, X and
      Y = other coordination sites) were synthesized using photoisomerization of a
      mononuclear complex. The p,p-Ru2XY complexes undergo unusual reversible bridge
      exchange reactions to generate p,p-Ru2(MU-Cl), p,p-Ru2(MU-OH), and p,p
      Ru2(OH)(OH2) with MU-Cl, MU-OH, as well as hydroxo and aquo ligands at X and Y
      sites of p,p-Ru2XY, respectively. The geometric and electronic structures of
      these complexes were characterized based on UV-vis and (1)H NMR spectra, X-ray
      crystallography, and density functional theory (DFT) calculations. (1)H NMR data
      showed C2 symmetry of p,p-Ru2(OH)(OH2) with the distorted L chelate and
      nonequivalence of two tpy ligands, in contrast to the C2v symmetry of p,p-Ru2(MU
      Cl) and p,p-Ru2(MU-OH). However, irrespective of the lower symmetry, p,p
      Ru2(OH)(OH2) is predominantly formed in neutral and weakly basic conditions due
      to the specially stabilized core structure by multiple hydrogen-bond interactions
      among aquo, hydroxo, and backbone L ligands. The electrochemical data suggested
      that p,p-Ru2(OH)(OH2) (Ru(II)-OH:Ru(II)-OH2) is oxidized to the Ru(III)
      OH:Ru(III)-OH state at 0.64 V vs saturated calomel electrode (SCE) and further to
      Ru(IV)?O:Ru(IV)-OH at 0.79 V by successive 1-proton-coupled 2-electron processes
      at pH 7.0. The cyclic voltammogram data exhibited that the p,p-Ru2(OH)(OH2)
      complex works more efficiently for electrocatalytic water oxidation, compared
      with a similar mononuclear complex distal-[Ru(tpy)(L)OH2](2+) (d-RuOH2) and p,p
      Ru2(MU-Cl) and p,p-Ru2(MU-OH), showing that the p,p-Ru2 core structure with aquo
      and hydroxo ligands is important for efficient electrocatalytic water oxidation.
      Bulk electrolysis of the p,p-Ru2(OH)(OH2) solution corroborated the
      electrocatalytic cycle involving the Ru(III)-OH:Ru(III)-OH state species as a
      resting state. The mechanistic insight into O-O bond formation for O2 production
      was provided by the isotope effect on electrocatalytic water oxidation by p,p
      Ru2(OH)(OH2) and d-RuOH2 in H2O and D2O media. 

PMID- 26200107
TI  - Balancing Conservation with National Development: A Socio-Economic Case Study of
      the Alternatives to the Serengeti Road.
AB  - Developing countries often have rich natural resources but poor infrastructure to
      capitalize on them, which leads to significant challenges in terms of balancing
      poverty alleviation with conservation. The underlying premise in development
      strategies is to increase the socio-economic welfare of the people while
      simultaneously ensuring environmental sustainability, however these objectives
      are often in direct conflict. National progress is dependent on developing
      infrastructure such as effective transportation networks, however roads can be
      ecologically catastrophic in terms of disrupting habitat connectivity and
      facilitating illegal activity. How can national development and conservation be
      balanced? The proposed Serengeti road epitomizes the conflict between poverty
      alleviation on one hand, and the conservation of a critical ecosystem on the
      other. We use the Serengeti as an exemplar case-study in which the relative
      economic and social benefits of a road can be assessed against the ecological
      impacts. Specifically, we compare three possible transportation routes and ask
      which route maximizes the socio-economic returns for the people while minimizing
      the ecological costs. The findings suggest that one route in particular that
      circumnavigates the Serengeti links the greatest number of small and medium sized
      entrepreneurial businesses to the largest labour force in the region.
      Furthermore, this route connects the most children to schools, provisions the
      greatest access to hospitals, and opens the most fertile crop and livestock
      production areas, and does not compromise the ecology and tourism revenue of the
      Serengeti. This route would improve Tanzania's food security and self-reliance
      and would facilitate future infrastructure development which would not be
      possible if the road were to pass through the Serengeti. This case study provides
      a compelling example of how a detailed spatial analysis can balance the national
      objectives of poverty alleviation while maintaining ecological integrity. 

PMID- 26200108
TI  - Influence of the PNPLA3 rs738409 Polymorphism on Non-Alcoholic Fatty Liver
      Disease and Renal Function among Normal Weight Subjects.
AB  - In normal weight subjects (body mass index < 25 kg/m2), non-alcoholic fatty liver
      disease (NAFLD) is likely to coexist with metabolic diseases. The patatin-like
      phospholipase 3 (PNPLA3) polymorphism rs738409 (c.444C>G) is associated with the
      risk of NAFLD and/or renal dysfunction; however, the influence of the weight
      status on the associations remains unknown. We aimed to clarify the associations
      of the PNPLA3 polymorphism with the risk of NAFLD and/or renal dysfunction, while
      also paying careful attention to the weight status of the subjects. Cross
      sectional and retrospective longitudinal studies with 5.5 +/- 1.1 years of follow
      up were conducted in 740 and 393 Japanese participants (61.2 +/- 10.5 and 67.5 +/
      6.0 years), respectively, during a health screening program. Among 591 subjects
      who did not have a habitual alcohol intake and/or hepatitis B or C virus
      infections, the PNPLA3 G/G genotype was associated with the risk for NAFLD in
      normal weight subjects [odds ratio (95% CI): 3.06 (1.11-8.43), P < 0.05]. Among
      all subjects, carriers of the PNPLA3 G/G genotype with a normal weight had a
      lower eGFR than those of the C/C genotype [partial regression coefficient (SE): 
      3.26 (1.48), P < 0.05]. These associations were replicated in the longitudinal
      analyses. Among the overweight subjects, none of the genotypes were significantly
      associated in the cross-sectional and longitudinal analyses; however, the power
      of the analyses was small, especially in the analyses among overweight subjects.
      The findings of this study suggest that carriers of the PNPLA3 G/G genotype with
      a normal weight status should nevertheless be carefully monitored for the
      presence of NAFLD and/or renal dysfunction. 

PMID- 26200109
TI  - Network Analysis for the Identification of Differentially Expressed Hub Genes
      Using Myogenin Knock-down Muscle Satellite Cells.
AB  - Muscle, a multinucleate syncytium formed by the fusion of mononuclear myoblasts,
      arises from quiescent progenitors (satellite cells) via activation of muscle
      specific transcription factors (MyoD, Myf5, myogenin: MYOG, and MRF4). Subsequent
      to a decline in Pax7, induction in the expression of MYOG is a hallmark of
      myoblasts that have entered the differentiation phase following cell cycle
      withdrawal. It is evident that MYOG function cannot be compensated by any other
      myogenic regulatory factors (MRFs). Despite a plethora of information available
      regarding MYOG, the mechanism by which MYOG regulates muscle cell differentiation
      has not yet been identified. Using an RNA-Seq approach, analysis of MYOG knock
      down muscle satellite cells (MSCs) have shown that genes associated with cell
      cycle and division, DNA replication, and phosphate metabolism are differentially
      expressed. By constructing an interaction network of differentially expressed
      genes (DEGs) using GeneMANIA, cadherin-associated protein (CTNNA2) was identified
      as the main hub gene in the network with highest node degree. Four functional
      clusters (modules or communities) were identified in the network and the
      functional enrichment analysis revealed that genes included in these clusters
      significantly contribute to skeletal muscle development. To confirm this finding,
      in vitro studies revealed increased expression of CTNNA2 in MSCs on day 12
      compared to day 10. Expression of CTNNA2 was decreased in MYOG knock-down cells.
      However, knocking down CTNNA2, which leads to increased expression of
      extracellular matrix (ECM) genes (type I collagen alpha1 and type I collagen
      alpha2) along with myostatin (MSTN), was not found significantly affecting the
      expression of MYOG in C2C12 cells. We therefore propose that MYOG exerts its
      regulatory effects by acting upstream of CTNNA2, which in turn regulates the
      differentiation of C2C12 cells via interaction with ECM genes. Taken together,
      these findings highlight a new mechanism by which MYOG interacts with CTNNA2 in
      order to promote myoblast differentiation. 

PMID- 26200111
TI  - Effects of Approach-Avoidance Training on the Extinction and Return of Fear
      Responses.
AB  - BACKGROUND AND OBJECTIVES: Exposure therapy for anxiety involves confronting a
      patient with fear-evoking stimuli, a procedure based partially on Pavlovian
      extinction. Exposure and other extinction-based therapies usually lead to
      (partial) reduction of fear symptoms, but a substantial number of patients
      experience a return of fear after treatment. Here we tested whether the
      combination of fear extinction with modification of approach-avoidance tendencies
      using an Approach-Avoidance Task (AAT) would result in the further reduction of
      conditioned fear and/or help prevent return of fear after extinction. METHODS:
      Two groups of participants underwent a fear acquisition procedure during which
      pictures of one neutral object were sometimes paired with shock (CS+), whereas
      pictures of another neutral object were not (CS-). The next day, in a fear
      extinction procedure, both objects were presented without shock. During the
      subsequent joystick AAT, one group primarily pulled CS+ pictures towards
      themselves and pushed CS- pictures away from themselves; reversed contingencies
      applied for the other group. RESULTS: Approach training was effective in
      modifying conditioned action tendencies, with some evidence for transfer to a
      different approach/avoidance task. No group differences in subjective fear or
      physiological arousal were found during subsequent post- training and return-of
      fear testing. LIMITATIONS: No reliable return-of-fear was observed in either
      group for either subjective or physiological fear measures. CONCLUSIONS: Our
      results suggest that approach training may be of limited value for enhancing the
      short- and long-term effects of extinction-based interventions.

PMID- 26200112
TI  - Entorrhizomycota: A New Fungal Phylum Reveals New Perspectives on the Evolution
      of Fungi.
AB  - Entorrhiza is a small fungal genus comprising 14 species that all cause galls on
      roots of Cyperaceae and Juncaceae. Although this genus was established 130 years
      ago, crucial questions on the phylogenetic relationships and biology of this
      enigmatic taxon are still unanswered. In order to infer a robust hypothesis about
      the phylogenetic position of Entorrhiza and to evaluate evolutionary trends,
      multiple gene sequences and morphological characteristics of Entorrhiza were
      analyzed and compared with respective findings in Fungi. In our comprehensive
      five-gene analyses Entorrhiza appeared as a highly supported monophyletic lineage
      representing the sister group to the rest of the Dikarya, a phylogenetic
      placement that received but moderate maximum likelihood and maximum parsimony
      bootstrap support. An alternative maximum likelihood tree with the constraint
      that Entorrhiza forms a monophyletic group with Basidiomycota could not be
      rejected. According to the first phylogenetic hypothesis, the teliospore tetrads
      of Entorrhiza represent the prototype of the dikaryan meiosporangium. The
      alternative hypothesis is supported by similarities in septal pore structure,
      cell wall and spindle pole bodies. Based on the isolated phylogenetic position of
      Entorrhiza and its peculiar combination of features related to ultrastructure and
      reproduction mode, we propose a new phylum Entorrhizomycota, for the genus
      Entorrhiza, which represents an apparently widespread group of inconspicuous
      fungi. 

PMID- 26200110
TI  - Population Genetic Structure of the Dwarf Seahorse (Hippocampus zosterae) in
      Florida.
AB  - The dwarf seahorse (Hippocampus zosterae) is widely distributed throughout near
      shore habitats of the Gulf of Mexico and is of commercial significance in
      Florida, where it is harvested for the aquarium and curio trades. Despite its
      regional importance, the genetic structure of dwarf seahorse populations remains
      largely unknown. As an aid to ongoing conservation efforts, we employed three
      commonly applied mtDNA markers (ND4, DLoop and CO1) to investigate the genetic
      structuring of H. zosterae in Florida using samples collected throughout its
      range in the state. A total of 1450 bp provided sufficient resolution to
      delineate four populations of dwarf seahorses, as indicated by significant
      fixation indices. Despite an overall significant population structure, we
      observed evidence of interbreeding between individuals from geographically
      distant sites, supporting the hypothesis that rafting serves to maintain a degree
      of population connectivity. All individuals collected from Pensacola belong to a
      single distinct subpopulation, which is highly differentiated from the rest of
      Floridian dwarf seahorses sampled. Our findings highlight the utility of mtDNA
      markers in evaluating barriers to gene flow and identifying genetically distinct
      populations, which are vital to the development of comprehensive conservation
      strategies for exploited taxa. 

PMID- 26200115
TI  - Phylogeny of Kinorhyncha Based on Morphology and Two Molecular Loci.
AB  - The phylogeny of Kinorhyncha was analyzed using morphology and the molecular loci
      18S rRNA and 28S rRNA. The different datasets were analyzed separately and in
      combination, using maximum likelihood and Bayesian Inference. Bayesian inference
      of molecular sequence data in combination with morphology supported the division
      of Kinorhyncha into two major clades: Cyclorhagida comb. nov. and Allomalorhagida
      nom. nov. The latter clade represents a new kinorhynch class, and accommodates
      Dracoderes, Franciscideres, a yet undescribed genus which is closely related with
      Franciscideres, and the traditional homalorhagid genera. Homalorhagid monophyly
      was not supported by any analyses with molecular sequence data included. Analysis
      of the combined molecular and morphological data furthermore supported a
      cyclorhagid clade which included all traditional cyclorhagid taxa, except
      Dracoderes that no longer should be considered a cyclorhagid genus. Accordingly,
      Cyclorhagida is divided into three main lineages: Echinoderidae, Campyloderidae,
      and a large clade, 'Kentrorhagata', which except for species of Campyloderes,
      includes all species with a midterminal spine present in adult individuals.
      Maximum likelihood analysis of the combined datasets produced a rather unresolved
      tree that was not regarded in the following discussion. Results of the analyses
      with only molecular sequence data included were incongruent at different points.
      However, common for all analyses was the support of several major clades, i.e.,
      Campyloderidae, Kentrorhagata, Echinoderidae, Dracoderidae, Pycnophyidae, and a
      clade with Paracentrophyes + New Genus and Franciscideres (in those analyses
      where the latter was included). All molecular analyses including 18S rRNA
      sequence data furthermore supported monophyly of Allomalorhagida. Cyclorhagid
      monophyly was only supported in analyses of combined 18S rRNA and 28S rRNA (both
      ML and BI), and only in a restricted dataset where taxa with incomplete
      information from 28S rRNA had been omitted. Analysis of the morphological data
      produced results that were similar with those from the combined molecular and
      morphological analysis. E.g., the morphological data also supported exclusion of
      Dracoderes from Cyclorhagida. The main differences between the morphological
      analysis and analyses based on the combined datasets include: 1) Homalorhagida
      appears as monophyletic in the morphological tree only, 2) the morphological
      analyses position Franciscideres and the new genus within Cyclorhagida near
      Zelinkaderidae and Cateriidae, whereas analyses including molecular data place
      the two genera inside Allomalorhagida, and 3) species of Campyloderes appear in a
      basal trichotomy within Kentrorhagata in the morphological tree, whereas analysis
      of the combined datasets places species of Campyloderes as a sister clade to
      Echinoderidae and Kentrorhagata. 

PMID- 26200114
TI  - Integrative Analysis of the Developing Postnatal Mouse Heart Transcriptome.
AB  - In mammals, cardiomyocytes rapidly proliferate in the fetus and continue to do so
      for a few more days after birth. These cardiomyocytes then enter into growth
      arrest but the detailed molecular mechanisms involved have not been fully
      elucidated. We have addressed this issue by comparing the transcriptomes of 2-day
      old (containing dividing cardiomyocytes) with 13-day-old (containing growth
      arrested cardiomyocytes) postnatal mouse hearts. We performed comparative
      microarray analysis on the heart tissues and then conducted Functional
      annotation, Gene ontology, KEGG pathway and Gene Set enrichment analyses on the
      differentially expressed genes. The bioinformatics analysis revealed that gene
      ontology categories associated with the "cell cycle", "DNA replication",
      "chromosome segregation" and "microtubule cytoskeleton" were down-regulated.
      Inversely, "immune response", "extracellular matrix", "cell differentiation" and
      "cell membrane" were up-regulated. Ingenuity Pathways Analysis (IPA) has revealed
      that GATA4, MYH7 and IGF1R were the key drivers of the gene interaction networks.
      In addition, Regulator Effects network analysis suggested that TASP1, TOB1,
      C1orf61, AIF1, ROCK1, TFF2 and miR503-5p may be acting on the cardiomyocytes in
      13-day-old mouse hearts to inhibit cardiomyocyte proliferation and G1/S phase
      transition. RT-qPCR was used to validate genes which were differentially
      expressed and genes that play a prominent role in the pathways and interaction
      networks that we identified. In sum, our integrative analysis has provided more
      insights into the transcriptional regulation of cardiomyocyte exit from the cell
      cycle during postnatal heart development. The results also pinpoint potential
      regulators that could be used to induce growth arrested cardiomyocytes to
      proliferate in the infarcted heart. 

PMID- 26200113
TI  - Glycoengineered Monoclonal Antibodies with Homogeneous Glycan (M3, G0, G2, and
      A2) Using a Chemoenzymatic Approach Have Different Affinities for FcgammaRIIIa
      and Variable Antibody-Dependent Cellular Cytotoxicity Activities.
AB  - Many therapeutic antibodies have been developed, and IgG antibodies have been
      extensively generated in various cell expression systems. IgG antibodies contain
      N-glycans at the constant region of the heavy chain (Fc domain), and their N
      glycosylation patterns differ during various processes or among cell expression
      systems. The Fc N-glycan can modulate the effector functions of IgG antibodies,
      such as antibody-dependent cellular cytotoxicity (ADCC) and complement dependent
      cytotoxicity (CDC). To control Fc N-glycans, we performed a rearrangement of Fc N
      glycans from a heterogeneous N-glycosylation pattern to homogeneous N-glycans
      using chemoenzymatic approaches with two types of endo-beta-N-acetyl
      glucosaminidases (ENG'ases), one that works as a hydrolase to cleave all
      heterogeneous N-glycans, another that is used as a glycosynthase to generate
      homogeneous N-glycans. As starting materials, we used an anti-Her2 antibody
      produced in transgenic silkworm cocoon, which consists of non-fucosylated pauci
      mannose type (Man2-3GlcNAc2), high-mannose type (Man4-9GlcNAc2), and complex type
      (Man3GlcNAc3-4) N-glycans. As a result of the cleavage of several ENG'ases
      (endoS, endoM, endoD, endoH, and endoLL), the heterogeneous glycans on antibodies
      were fully transformed into homogeneous-GlcNAc by a combination of endoS, endoD,
      and endoLL. Next, the desired N-glycans (M3; Man3GlcNAc1, G0; GlcNAc2Man3GlcNAc1,
      G2; Gal2GlcNAc2Man3GlcNAc1, A2; NeuAc2Gal2GlcNAc2Man3GlcNAc1) were transferred
      from the corresponding oxazolines to the GlcNAc residue on the intact anti-Her2
      antibody with an ENG'ase mutant (endoS-D233Q), and the glycoengineered anti-Her2
      antibody was obtained. The binding assay of anti-Her2 antibody with homogenous N
      glycans with FcgammaRIIIa-V158 showed that the glycoform influenced the affinity
      for FcgammaRIIIa-V158. In addition, the ADCC assay for the glycoengineered anti
      Her2 antibody (mAb-M3, mAb-G0, mAb-G2, and mAb-A2) was performed using SKBR-3 and
      BT-474 as target cells, and revealed that the glycoform influenced ADCC activity.

PMID- 26200117
TI  - Transport Properties of Amine/Carbon Dioxide Reactive Mixtures and Implications
      to Carbon Capture Technologies.
AB  - The structure and transport properties of physisorbed and chemisorbed CO2 in
      model polyamine liquids (hexamethylenediamine and diethylenetriamine) are studied
      via molecular dynamics simulations. Such systems are relevant to CO2 absorption
      processes where nonaqueous amines are used as absorbents (e.g., when impregnated
      or grafted onto mesoporous media or misted in the gas phase). It is shown that
      accounting for the ionic speciation resulting from CO2 chemisorption enabled us
      to capture the qualitative changes in extent of absorption and fluidity with time
      that are observed in thermogravimetric experiments. Simulations reveal that high
      enough concentration of reacted CO2 leads to strong intermolecular ionic
      interactions and the arrest of molecular translations. The transport properties
      obtained from the simulations of the ionic speciated mixtures are also used to
      construct an approximate continuum-level model for the CO2 absorption process
      that mimics thermogravimetric experiments. 

PMID- 26200116
TI  - Increased Dietary Intake of Saturated Fatty Acid Heptadecanoic Acid (C17:0)
      Associated with Decreasing Ferritin and Alleviated Metabolic Syndrome in
      Dolphins.
AB  - Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic
      syndrome and associated high ferritin. While fish and fish-based fatty acids may
      protect against metabolic syndrome in humans, findings have been inconsistent. To
      assess potential protective factors against metabolic syndrome related to fish
      diets, fatty acids were compared between two dolphin populations with higher (n =
      30, Group A) and lower (n = 19, Group B) mean insulin (11 +/- 12 and 2 +/- 5
      MUIU/ml, respectively; P < 0.0001) and their dietary fish. In addition to higher
      insulin, triglycerides, and ferritin, Group A had lower percent serum
      heptadecanoic acid (C17:0) compared to Group B (0.3 +/- 0.1 and 1.3 +/- 0.4%,
      respectively; P < 0.0001). Using multivariate stepwise regression, higher percent
      serum C17:0, a saturated fat found in dairy fat, rye, and some fish, was an
      independent predictor of lower insulin in dolphins. Capelin, a common dietary
      fish for Group A, had no detectable C17:0, while pinfish and mullet, common in
      Group B's diet, had C17:0 (41 and 67 mg/100g, respectively). When a modified diet
      adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks
      (increasing the average daily dietary C17:0 intake from 400 to 1700 mg), C17:0
      serum levels increased, high ferritin decreased, and blood-based metabolic
      syndrome indices normalized toward reference levels. These effects were not found
      in four reference dolphins. Further, higher total serum C17:0 was an independent
      and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off
      the shelf dairy products tested, butter had the highest C17:0 (423mg/100g);
      nonfat dairy products had no detectable C17:0. We hypothesize that humans'
      movement away from diets with potentially beneficial saturated fatty acid C17:0,
      including whole fat dairy products, could be a contributor to widespread low
      C17:0 levels, higher ferritin, and metabolic syndrome. 

PMID- 26200118
TI  - Active Treatment for Idiopathic Adolescent Scoliosis (ACTIvATeS): a feasibility
      study.
AB  - BACKGROUND: The feasibility of conducting a definitive randomised controlled
      trial (RCT) evaluating the clinical effectiveness and cost-effectiveness of
      scoliosis-specific exercises (SSEs) for adolescent idiopathic scoliosis (AIS) is
      uncertain. OBJECTIVES: The aim of this study was to assess the feasibility of
      conducting a large, multicentre trial of SSE treatment for patients with AIS, in
      comparison with standard care, and to refine elements of the study design. The
      objectives were to (1) update a systematic review of controlled trials evaluating
      the efficacy of SSE in AIS; (2) survey UK orthopaedic surgeons and
      physiotherapists to determine current practice, patient populations and
      equipoise; (3) randomise 50 adolescents to a feasibility trial of either usual
      care or SSE interventions across a range of sites; (4) develop, document and
      assess acceptability and adherence of interventions; (5) assess and describe
      training requirements of physiotherapists; and (6) gain user input in all
      relevant stages of treatment and protocol design. DESIGN: Multicomponent
      feasibility study including UK clinician survey, systematic literature review and
      a randomised feasibility trial. SETTING: The randomised feasibility study
      involved four secondary care NHS trusts providing specialist care for patients
      with AIS. PARTICIPANTS: The randomised feasibility study recruited people aged 10
      16 years with mild AIS (Cobb angle of < 50 degrees ). INTERVENTIONS: The
      randomised study allocated participants to standard practice of advice and
      education or a physiotherapy SSE programme supported by a home exercise plan. Our
      choice of intervention was informed by a systematic review of exercise
      interventions for AIS. MAIN OUTCOME MEASURES: The main outcome was feasibility of
      recruitment to the randomised study. Other elements were to inform choice of
      outcomes for a definitive trial and included curve severity, quality of life,
      requirement for surgery/brace, adverse events, psychological symptoms, costs and
      health utilities. RESULTS: A UK survey of orthopaedic consultants and
      physiotherapists indicated a wide variation in current provision of exercise
      therapy through physiotherapy services. It also found that clinicians from at
      least 15 centres would be willing to have their patients involved in a full
      study. A systematic review update found five new studies that were generally of
      low quality but showed some promise of effectiveness of SSE. The randomised study
      recruited 58 patients from four NHS trusts over 11 months and exceeded the pre
      specified target recruitment rate of 1.4 participants per centre per month, with
      acceptable 6-month follow-up (currently 73%). Adherence to treatment was variable
      (56% of participants completed treatment offered). The qualitative study found
      the exercise programme to be highly acceptable. We learnt important lessons from
      patient and public involvement during the study in terms of study and
      intervention presentation, as well as practical elements such as scheduling of
      intervention sessions. CONCLUSIONS: A definitive RCT evaluating clinical
      effectiveness and cost-effectiveness of SSE for idiopathic scoliosis is warranted
      and feasible. Such a RCT is a priority for future work in the area. There is a
      sufficiently large patient base, combined with willingness to be randomised
      within specialist UK centres. Interventions developed during the feasibility
      study were acceptable to patients, families and physiotherapists and can be given
      within the affordability envelope of current levels of physiotherapy
      commissioning. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90480705.
      FUNDING: This project was funded by the NIHR Health Technology Assessment
      programme and will be published in full in Health Technology Assessment; Vol. 19,
      No. 55. See the NIHR Journals Library website for further project information.

PMID- 26200119
TI  - An integrated methodology for the assessment of environmental health implications
      during thermal decomposition of nano-enabled products.
AB  - The proliferation of nano-enabled products (NEPs) renders human exposure to
      engineered nanomaterials (ENMs) inevitable. Over the last decade, the risk
      assessment paradigm for nanomaterials focused primarily on potential adverse
      effect of pristine, as-prepared ENMs. However, the physicochemical properties of
      ENMs may be drastically altered across their life-cycle (LC), especially when
      they are embedded in various NEP matrices. Of a particular interest is the end-of
      life scenario by thermal decomposition. The main objective of the current study
      is to develop a standardized, versatile and reproducible methodology that allows
      for the systematic physicochemical and toxicological characterization of the NEP
      thermal decomposition. The developed methodology was tested for an industry
      relevant NEP in order to verify its versatility for such LC investigations.
      Results are indicative of potential environmental health risks associated with
      waste from specific NEP families and prompt for the development of safer-by
      design approaches and exposure control strategies.

PMID- 26200120
TI  - Determining Outcomes After Traumatic Brain Injury.

PMID- 26200121
TI  - Short peptides allowing preferential detection of Candida albicans hyphae.
AB  - Whereas the detection of pathogens via recognition of surface structures by
      specific antibodies and various types of antibody mimics is frequently described,
      the applicability of short linear peptides as sensor molecules or diagnostic
      tools is less well-known. We selected peptides which were previously reported to
      bind to recombinant S. cerevisiae cells, expressing members of the C. albicans
      Agglutinin-Like-Sequence (ALS) cell wall protein family. We slightly modified
      amino acid sequences to evaluate peptide sequence properties influencing binding
      to C. albicans cells. Among the selected peptides, decamer peptides with an "AP"
      N-terminus were superior to shorter peptides. The new decamer peptide FBP4
      stained viable C. albicans cells more efficiently in their mature hyphal form
      than in their yeast form. Moreover, it allowed distinction of C. albicans from
      other related Candida spp. and could thus be the basis for the development of a
      useful tool for the diagnosis of invasive candidiasis. 

PMID- 26200122
TI  - Effects of Two Short-Term, Intermittent Hypoxic Training Protocols on the Finger
      Temperature Response to Local Cold Stress.
AB  - The study examined the effects of two short-term, intermittent hypoxic training
      protocols, namely exercising in hypoxia and living in normoxia (LL-TH; n=8), and
      exercising in normoxia preceded by a series of brief intermittent hypoxic
      exposures at rest (IHE+NOR; n=8), on the finger temperature response during a sea
      level local cold test. In addition, a normoxic group was assigned as a control
      group (NOR; n=8). All groups trained on a cycle-ergometer 1 h/day, 5 days/week
      for 4 weeks at 50% of peak power output. Pre, post, and 11 days after the last
      training session, subjects immersed their right hand for 30 min in 8 degrees C
      water. In the NOR group, the average finger temperature was higher in the post
      (+2.1 degrees C) and 11-day after (+2.6 degrees C) tests than in the pre-test
      (p<=0.001). Conversely, the fingers were significantly colder immediately after
      both hypoxic protocols (LL-TH: -1.1 degrees C, IHE+NOR: -1.8 degrees C; p=0.01).
      The temperature responses returned to the pre-training level 11 days after the
      hypoxic interventions. Ergo, present findings suggest that short-term
      intermittent hypoxic training impairs sea-level local cold tolerance; yet, the
      hypoxic-induced adverse responses seem to be reversible within a period of 11
      days.

PMID- 26200123
TI  - Protein-Protein Interactions in the Cyanobacterial Circadian Clock: Structure of
      KaiA Dimer in Complex with C-Terminal KaiC Peptides at 2.8 A Resolution.
AB  - In the cyanobacterial circadian clock, the KaiA, -B, and -C proteins with ATP
      constitute a post-translational oscillator. KaiA stimulates the KaiC autokinase,
      and KaiB antagonizes KaiA action. KaiA contacts the intrinsically disordered C
      terminal regions of KaiC hexamer to promote phosphorylation across subunit
      interfaces. The crystal structure of KaiA dimer from Synechococcus elongatus with
      two KaiC C-terminal 20mer peptides bound reveals that the latter adopt an alpha
      helical conformation and contact KaiA alpha-helical bundles via mostly
      hydrophobic interactions. This complex and the crystal structure of KaiC hexamer
      with truncated C-terminal tails can be fit into the electron microscopy (EM)
      density of the KaiA:KaiC complex. The hybrid model helps rationalize clock
      phenotypes of KaiA and KaiC mutants. 

PMID- 26200124
TI  - [Analysis of the Design of the Ascension(r) PyroCarbon PIP Total Joint Proximal
      Component in Relation to the Proximal Phalanx Morphology].
AB  - BACKGROUND: There are many indications that long-term stability of the
      Ascension((r)) pyrocarbon proximal interphalangeal (PIP) total joint is not
      attained by osseointegration but by appositional bone formation. Accordingly,
      good locking by cortical bone for sufficient primary stability is necessary in
      order to avoid prosthesis loosening before enough new bone has been formed. The
      size of the proximal component of the Ascension((r)) PyroCarbon PIP total joint
      and thus cortical anchorage and primary stability depend on the morphology of the
      proximal finger phalanx and, especially, on the isthmus of the distal medullary
      canal. OBJECTIVE: To clarify whether the medullary canal of the proximal finger
      phalanx can be enlarged using the Ascension((r)) pyrocarbon PIP total joint
      instruments so that cortical contact of the proximal prosthesis component is
      guaranteed in the region of the isthmus in both sagittal and frontal planes.
      MATERIAL UND METHODEN: Before insertion of the Ascension((r)) pyrocarbon PIP
      total joint prosthesis, the isthmus widths of the proximal phalanx of 138 cadaver
      fingers were measured on radiographs by fluoroscopy in both the frontal and
      sagittal plane. The measured dimensions were compared to the dimensions of the
      inserted proximal component stems (manufacturer's instructions) after preparation
      of the medullary canal. The largest prosthesis possible was always used. RESULTS:
      The mean isthmus width of the index fingers on PA view was 3.4 mm (2.4-4.2), of
      the middle fingers 3.3 mm (1.8-4.6), of the ring fingers 3.2 mm (2.2-4.7), and of
      the small fingers 2.9 mm (1.4-4.3). The mean isthmus width of the index fingers
      on lateral view was 2.6 mm (1.6-3.7), of the middle fingers 2.5 mm (1.8-3.8), of
      the ring fingers 2.3 mm (1.5-3.6), and of the small fingers 2.0 mm (1.4-2.8).
      There were statistically significant differences between the isthmus widths
      measured before insertion and the stem dimensions of the inserted proximal
      components. While the average width of the isthmus in the index, middle, ring,
      and little fingers was significantly larger than the stem width of the inserted
      proximal components, the average isthmus height was significantly smaller than
      the stem height of the inserted proximal components. CONCLUSION: Ideal cortical
      contact between the isthmus of the proximal phalanx and the largest proximal
      component of the Ascension((r)) pyrocarbon PIP total joint prosthesis that can be
      inserted, and thus good primary stability, is not possible due to a mismatch in
      the frontal plane between the morphology of the proximal phalanx and the
      prosthesis. But good contact can be achieved in the sagittal plane by broaching
      the medullary canal.

PMID- 26200125
TI  - Fate and Transport of Phthalates in Indoor Environments and the Influence of
      Temperature: A Case Study in a Test House.
AB  - A case study in a test house was conducted to investigate the fate and transport
      of benzyl butyl phthalate (BBzP) and di-2-ethylhexyl phthalate (DEHP) in
      residential indoor environments and the influence of temperature. Total airborne
      concentrations of phthalates were sensitive to indoor temperatures, and their
      steady-state concentration levels increased by a factor of 3 with an increase in
      temperature from 21 to 30  degrees C. Strong sorption of phthalates was observed
      on interior surfaces, including dust, dish plates, windows, mirrors, fabric
      cloth, and wood. Equilibrium partitioning coefficients for phthalates adsorbed to
      these surfaces were determined, and their values decreased with increasing
      temperature. For impervious surfaces, dimensionless partitioning coefficients
      were calculated and found to be comparable to reported values of the octanol-air
      partition coefficients of phthalates, Koa, suggesting that an organic film may
      develop on these surfaces. In addition, sorption kinetics was studied
      experimentally, and the equilibration time scale for impervious surfaces was
      found to be faster than that of fabric cloth. Finally, using an indoor fate model
      to interpret the measurement results, there was good agreement between model
      predictions and the observed indoor air concentrations of BBzP in the test house.

PMID- 26200126
TI  - Bromination of Graphene: A New Route to Making High Performance Transparent
      Conducting Electrodes with Low Optical Losses.
AB  - The unique optical and electrical properties of graphene have triggered great
      interest in its application as a transparent conducting electrode material and
      significant effort has been invested in achieving high conductivity while
      maintaining high transparency. Doping of graphene has been a popular route for
      reducing its sheet resistance, but this has typically come at a significant loss
      in optical transmittance. We demonstrate doping of few layers graphene (FLG) with
      bromine as a means of enhancing the conductivity via intercalation without major
      optical losses. Our results demonstrate the encapsulation of bromine within the
      FLG, leading to air-stable transparent conducting electrodes with 5-fold
      improvement of sheet resistance reaching ~180 Omega/? at the cost of only 2-3%
      loss of optical transmittance. The remarkably low trade-off in optical
      transparency leads to the highest enhancements in the figure of merit reported
      thus far for FLG. Furthermore, we tune the work function by up to 0.3 eV by
      tuning the bromine content. These results should help pave the way for further
      development of graphene as a potential substitute to transparent conducting
      polymers and metal oxides used in optoelectronics, photovoltaics, and beyond. 

PMID- 26200127
TI  - Advances and challenges in developing a therapy for spinal muscular atrophy.
AB  - Spinal muscular atrophy (SMA) is a debilitating and incurable childhood onset
      disease characterized by the degeneration of motor neurons in the spinal cord
      resulting in muscular atrophy and paralysis. Over the past 20 years, there has
      been significant progress in understanding the molecular basis of the disease,
      allowing researchers to identify the main causative gene and successfully model
      SMA in various animals. Despite an improved understanding of the disease, there
      is still no effective treatment for SMA patients. Here, we discuss the current
      knowledge surrounding the pathogenesis of SMA, and outline recent advances toward
      the development of a successful therapy for this devastating disease. 

PMID- 26200128
TI  - Minimally invasive treatment of intracerebral hemorrhage.
AB  - Intracerebral hemorrhages (ICH) cause high levels of morbidity and mortality.
      Secondary neuronal injury from perihematomal edema is thought to contribute to
      poor outcomes. Surgical evacuation of ICH is a theoretically promising approach,
      yet clinical data on the efficacy of standard craniotomy approaches is limited.
      Recent exploration of minimally invasive techniques for ICH removal includes
      stereotactic surgery combined with intra-clot thrombolysis, as well as endoscopic
      hematoma evacuation. Ongoing trials have demonstrated the safety of such
      minimally invasive approaches, and pending efficacy data from these studies is
      likely to change the standard management of ICH. 

PMID- 26200129
TI  - Mild Approach to 2-Acylfurans via Intercepted Meyer-Schuster Rearrangement of 6
      Hydroxyhex-2-en-4-ynals.
AB  - We have developed a mild, intramolecular intercepted Meyer-Schuster (M-S)
      rearrangement for the synthesis of 2-acylfurans from corresponding cis-6
      hydroxyhex-2-en-4-ynals. This reaction was found to be very general, and the
      starting materials are easily accessible. By this methodology the first synthesis
      of deoxy-nor-abiesesquine B, a sesquiterpene, was also achieved in three steps.
      The concept of adding two nucleophiles during the M-S rearrangement was
      introduced. 

PMID- 26200130
TI  - Thermoelectric Properties of Ag-Doped Bi2(Se,Te)3 Compounds: Dual Electronic
      Nature of Ag-Related Lattice Defects.
AB  - Effects of Ag doping and thermal annealing temperature on thermoelectric
      transport properties of Bi2(Se,Te)3 compounds are investigated. On the basis of
      the comprehensive analysis of carrier concentration, Hall mobility, and lattice
      parameter, we identified two Ag-related interstitial (Agi) and substitutional
      (AgBi) defects that modulate in different ways the thermoelectric properties of
      Ag-doped Bi2(Se,Te)3 compounds. When Ag content is less than 0.5 wt %, Agi plays
      an important role in stabilizing crystal structure and suppressing the formation
      of donor-like Te vacancy (VTe) defects, leading to the decrease in carrier
      concentration with increasing Ag content. For the heavily doped Bi2(Se,Te)3
      compounds (>0.5 wt % Ag), the increasing concentration of AgBi is held
      responsible for the increase of electron concentration because formation of AgBi
      defects is accompanied by annihilation of hole carriers. The analysis of Seebeck
      coefficients and temperature-dependent electrical properties suggests that
      electrons in Ag-doped Bi2(Se,Te)3 compounds are subject to a mixed mode of
      impurity scattering and lattice scattering. A 10% enhancement of thermoelectric
      figure-of-merit at room temperature was achieved for 1 wt % Ag-doped Bi2(Se,Te)3
      as compared to pristine Bi2(Se,Te)3. 

PMID- 26200131
TI  - Triterpenoids with Promoting Effects on the Differentiation of PC12 Cells from
      the Steamed Roots of Panax notoginseng.
AB  - The roots of Panax notoginseng, an important Chinese medicinal plant, have been
      used traditionally in both the raw and processed forms, due to the different
      chemical constituents and bioactivities found. Thirty-eight dammarane-type
      triterpenoid saponins were isolated from the steam-processed roots of P.
      notoginseng, including 18 new substances, namely, notoginsenosides SP1-SP18 (1
      18). The structures of 1-18 were determined on the basis of spectroscopic
      analysis and acidic hydrolysis. The absolute configuration of the hydroxy group
      at C-24 in 1-4, 19, and 20 was determined in each case by Mo2(AcO)4-induced
      circular dichroism. The new compounds were found to feature a diversity of highly
      oxygenated side chains, formed by hydrolysis of the C-20 sugar moiety followed by
      dehydration, dehydrogenation, epoxidation, hydroxylation, or methoxylation of the
      main saponins in the raw roots. The new saponins 1, 2, 6-8, 14, and 17 and the
      known compounds 20-27 showed promoting effects on the differentiation of PC12
      cells, at a concentration of 10 MUM. 

PMID- 26200132
TI  - Laparoscopic Hand-Assisted Parenchymal-Sparing Resections for Presumed Side
      Branch Intraductal Papillary Mucinous Neoplasms.
AB  - BACKGROUND: The diagnosis of side-branch intraductal papillary mucinous neoplasms
      (IMPNs) is increasingly more common, but their appropriate management is still
      evolving. We recently began performing laparoscopic hand-assisted enucleation or
      duodenal-sparing pancreatic head resection for these lesions with vigilant
      postoperative imaging. MATERIALS AND METHODS: Seventeen patients with pancreatic
      cystic lesions were included in this single-center retrospective review from
      January 1, 2008 to March 30, 2013. Indication for surgical intervention was
      growth in size of the cyst, symptoms, cyst size >3 cm, and/or presence of a mural
      nodule. Twelve patients underwent laparoscopic hand-assisted enucleation, and 5
      patients underwent laparoscopic hand-assisted pancreatic head resection. RESULTS:
      The mean age of patients was 64 years old. The most common presenting symptom was
      abdominal pain. The indication for surgical intervention was growth in the cyst
      or symptoms in the majority of patients. Fourteen lesions were in the
      head/uncinate, two were in the pancreatic body, and one was in the tail. Final
      pathology was consistent with side-branch IPMN in 13 patients (1 with focal
      adenocarcinoma). Three patients had serous cysts, and 1 had a mucinous cyst.
      Three patients developed pancreatic leaks, which were controlled with
      intraoperative placed drains, whereas 1 patient required additional drain
      placement. Median time from surgery to latest follow-up imaging is over 2 years.
      No patients have developed recurrent cysts or adenocarcinoma. CONCLUSIONS:
      Duodenal-sparing pancreatic head resection or pancreatic enucleation for patients
      with presumed side-branch IPMN is a safe and efficacious option, in terms of both
      operative outcomes and postoperative recurrence risk.

PMID- 26200134
TI  - Regional Pattern of Dementia and Prevalence of Hearing Impairment in Germany.
AB  - OBJECTIVES: To determine the association between hearing impairment and dementia.
      DESIGN: Cross-sectional study. SETTING: Claims data of the Allgemeine
      Ortskrankenkasse, the largest public health insurance company in Germany.
      PARTICIPANTS: Age-stratified sample of all insured persons aged 65 and above in
      the first quarter of 2007 (N = 1,338,462). MEASUREMENTS: Metaregression analysis
      on the association between regional prevalence of dementia and hearing impairment
      controlled for major vascular risk factors, including hypertension,
      hypercholesterolemia, diabetes mellitus, and cerebrovascular disease. Dementia
      and hearing impairment diagnoses were defined according to International
      Classification of Diseases, Tenth Revision, codes. Ninety-five regions were
      distinguished according to the two-digit postal code of the place of residence.
      RESULTS: A significant association was found between regional prevalences of
      dementia and hearing impairment that was preserved when controlling for major
      vascular risk factors (P = .003). Regional dementia prevalence increased by
      approximately 0.23% when the prevalence of hearing impairment increased by 1
      standard deviation. CONCLUSION: The relationship between hearing impairment and
      dementia has been repeatedly demonstrated on the individual level. The results of
      the current study confirm that this relationship also exists on a regional level.
      These findings underscore the potential role of hearing impairment as a risk
      factor for dementia that will be relevant for the management of elderly patients
      in general practice.

PMID- 26200133
TI  - Reduction of Acute Inflammatory Effects of Fumed Silica Nanoparticles in the Lung
      by Adjusting Silanol Display through Calcination and Metal Doping.
AB  - The production of pyrogenic (fumed) silica is increasing worldwide at a 7% annual
      growth rate, including expanded use in food, pharmaceuticals, and other
      industrial products. Synthetic amorphous silica, including fumed silica, has been
      generally recognized as safe for use in food products by the Food and Drug
      Administration. However, emerging evidence from experimental studies now suggests
      that fumed silica could be hazardous due to its siloxane ring structure, high
      silanol density, and "string-of-pearl-like" aggregate structure, which could
      combine to cause membrane disruption, generation of reactive oxygen species, pro
      inflammatory effects, and liver fibrosis. Based on this structure-activity
      analysis (SAA), we investigated whether calcination and rehydration of fumed
      silica changes its hazard potential in the lung due to an effect on silanol
      density display. This analysis demonstrated that the accompanying change in
      surface reactivity could indeed impact cytokine production in macrophages and
      acute inflammation in the lung, in a manner that is dependent on siloxane ring
      reconstruction. Confirmation of this SAA in vivo, prompted us to consider safer
      design of fumed silica properties by titanium and aluminum doping (0-7%), using
      flame spray pyrolysis. Detailed characterization revealed that increased Ti and
      Al doping could reduce surface silanol density and expression of three-membered
      siloxane rings, leading to dose-dependent reduction in hydroxyl radical
      generation, membrane perturbation, potassium efflux, NLRP3 inflammasome
      activation, and cytotoxicity in THP-1 cells. The reduction of NLRP3 inflammasome
      activation was also confirmed in bone-marrow-derived macrophages. Ti doping, and
      to a lesser extent Al doping, also ameliorated acute pulmonary inflammation,
      demonstrating the possibility of a safer design approach for fumed silica, should
      that be required for specific use circumstances. 

PMID- 26200135
TI  - A Nearly Ideal One-Dimensional S = 5/2 Antiferromagnet FeF3(4,4'-bpy) (4,4'-bpy
      =4,4'-bipyridyl) with Strong Intrachain Interactions.
AB  - An ideal one-dimensional (1D) magnet is expected to show exotic quantum
      phenomena. For compounds with larger S (S = 3/2, 2, 5/2, ...), however, a small
      interchain interaction J' tends to drive a conventional long-range ordered (LRO)
      state. Here, a new layered structure of FeF3(4,4'-bpy) (4,4'-bpy = 4,4'
      bipyridyl) with novel S = 5/2 (Fe(3+)) chains has been hydrothermally synthesized
      by using 4,4'-bpy to separate chains. The temperature-dependent susceptibility
      exhibits a broad maximum at high as 164 K, suggesting a fairly strong Fe-F-Fe
      intrachain interaction J. However, no anomaly associated with a LRO is seen in
      both magnetic susceptibility and specific heat even down to 2 K. This indicates
      an extremely small J' with J'/J < 3.2 * 10(-5), making this new material a nearly
      ideal 1D antiferromagnet. Mossbauer spectroscopy at 2.7 K reveals a critical
      slowing down of the 1D fluctuations toward a possible LRO at lower temperatures. 

PMID- 26200136
TI  - Pulling on super paramagnetic beads with micro cantilevers: single molecule
      mechanical assay application.
AB  - This paper demonstrates that it is possible to trap and release a super
      paramagnetic micro bead by fixing three super paramagnetic micro beads in a
      triangular array at the sensitive end of a micro cantilever, and by simply
      switching on/off an external magnetic field. To provide evidence of this
      principle we trap a micro bead that is attached to the free end of single DNA
      molecule and that has been previously fixed at the other end to a glass surface,
      using the standard sample preparation protocol of magnetic tweezers assays. The
      switching process is reversible which preserves the integrity of the tethered
      molecule, and a local force applied over the tethered bead excludes the
      neighbouring beads from the magnetic trap. We have developed a quadrature phase
      interferometer which is able to perform under fluid environments to accurately
      measure small deflections, which permits the exploration of DNA elasticity. Our
      results agree with measurements from magnetic tweezer assays performed under
      similar conditions. Furthermore, compared to the magnetic tweezer methodology,
      the combination of the magnetic trap with a suitable measurement system for
      cantilever deflection, allows for the exploration of a wide range of forces using
      a local method that has an improved temporal resolution. 

PMID- 26200137
TI  - Kolaviron Improves Morbidity and Suppresses Mortality by Mitigating Oxido
      Inflammation in BALB/c Mice Infected with Influenza Virus.
AB  - Influenza A viruses (IAV) induce cytokine storm and host's intracellular redox
      imbalance to ensure continuous replication and survival, leading to severe
      immunopathology and death. The unpredictability of broad-spectrum vaccines, the
      emergence of drug-resistant and/or more virulent strains, the prevalence of the
      amantadane-resistant IAV, and the prohibitive cost of available drugs especially
      in resource-poor countries necessitate exploring drugs with novel action
      mechanisms as anti-influenza agents. This study presents the protective role of
      kolaviron (KV), a natural antioxidant and anti-inflammatory agent from Garcinia
      kola seeds, on BALB/c mice challenged with influenza A/Perth/H3N2/16/09 (Pr/H3N2)
      virus. KV at 400 mg/kg was administered orally to groups of BALB/c mice for 3
      days, 3 h, and 1 h prior to infection with 1LD50 or 3LD50 (14-day study) and
      5LD50 (6-day study) Pr/H3N2. Pr/H3N2 in the lungs was detected by
      hemagglutination assay, while oxidative stress and inflammatory biomarkers were
      assayed in both lungs and liver. Infected mice treated with KV progressively
      increased in weight with minimal mortality. Single-dose administration of KV at 1
      h or 3 h before viral challenge and 3 days pretreatment improved lung aeration
      and reduced lung consolidation as well as inflammatory cells infiltration in a
      way that had minimal impact on viral clearance, but attenuated myeloperoxidase
      activity and nitric oxide production via priming of reduced glutathione levels,
      thus enhancing the preservation of function in the lungs and liver. This study
      suggests that KV may be effective for delaying the development of clinical
      symptoms of influenza virus, and this may be through a mechanism unrelated to
      those deployed by the existing anti-influenza drugs but closely associated to its
      antioxidant and immunomodulatory properties. 

PMID- 26200139
TI  - Direct microsuture repair of cerebral aneurysm neck avulsion: is this rescue
      technique really obsolete?

PMID- 26200138
TI  - The brain and the braincase: a spatial analysis on the midsagittal profile in
      adult humans.
AB  - The spatial relationships between brain and braincase represent a major topic in
      surgery and evolutionary neuroanatomy. In paleoneurology, neurocranial landmarks
      are often used as references for brain areas. In this study, we analyze the
      variation and covariation of midsagittal brain and skull coordinates in a sample
      of adult modern humans in order to demonstrate spatial associations between hard
      and soft tissues. The correlation between parietal lobe size and parietal bone
      size is very low, and there is a marked individual variation. The distances
      between lobes and bones are partially influenced by the dimensions of the
      parietal lobes. The main pattern of morphological variability among individuals,
      associated with the size of the precuneus, apparently does not influence the
      position of the neurocranial sutures. Therefore, variations in precuneal size
      modify the distance between the paracentral lobule and bregma, and between the
      parietal lobe and lambda. Hence, the relative position of the cranial and
      cerebral landmarks can change as a function of the parietal dimensions. The
      slight correlation and covariation among these elements suggests a limited degree
      of spatial integration between soft and hard tissues. Therefore, although the
      brain influences the cranial size and shape during morphogenesis, the specific
      position of the cerebral components is sensitive to multiple effects and local
      factors, without a strict correspondence with the bone landmarks. This absence of
      correspondent change between brain and skull boundaries suggests caution when
      making inferences about the brain areas from the position of the cranial sutures.
      The fact that spatial relationships between cranial and brain areas may vary
      according to brain proportions must be considered in paleoneurology, when brain
      anatomy is inferred from cranial evidence. 

PMID- 26200140
TI  - Bioinformatics analysis of the gene expression profiles in human intervertebral
      disc degeneration associated with inflammatory cytokines.
AB  - BACKGROUND: To investigate the microarray data on the gene expression profiles of
      intervertebral disc degeneration related to cytokine exposure. The purpose of the
      study was to identify the key genes that were differentially expressed in these
      disc cells compared to cells without inflammatory cytokine treatment, using
      bioinformatics analyses, and to explore the related signaling pathways and
      interaction networks, providing clues to the molecular mechanisms of disc
      degeneration for future experimental studies. METHODS: The gene expression
      profiles data were obtained using the same microarray platform for two groups of
      patients suffering from degenerative disc diseases: GSE41883 (Human annulus disc
      cells exposed to TNF-a; 4 samples) and GSE27494 (Human annulus disc cells exposed
      to IL-1beta; 4 samples). The genes that were differentially expressed in these
      two datasets compared to control disc cells (without cytokine exposure; 4 samples
      each) were identified using the R language, and were pooled using the Excel
      software program to select the common differentially expressed genes in the two
      datasets. The initial functional clustering, signaling pathways and protein
      protein interaction relationship analyses were conducted using the DAVID and
      STRING software programs. RESULTS: Of the 255 concomitantly and differentially
      expressed genes identified after respective treatment with TNF-alpha and IL
      1beta, 141 were up-regulated and 114 were down-regulated. The gene ontology
      annotation analysis showed that these differentially expressed genes were
      primarily associated with cytokine activity, growth factor activity, the
      inflammatory reaction and the response to injury. The signaling pathway analysis
      showed that these differentially expressed genes were mainly related to the
      interactions of cytokines, apoptosis and NOD-like receptor signaling pathways.
      The interaction network analysis indicated that PTGS2, ICAM1, NOV and other genes
      may play a role in disc degeneration. CONCLUSIONS: We found that ICAM1 and other
      genes may play a role in the development of disc degeneration induced by
      inflammatory reactions using a bioinformatics analysis of the gene expression
      profiles of degenerative intervertebral disc cells stimulated with inflammatory
      factors, suggesting that bioinformatics methods can be used to identify potential
      target for intervertebral disc degeneration.

PMID- 26200141
TI  - Mechanical stability of a novel screw design after repeated insertion: can the
      double-thread screw serve as a back up?
AB  - BACKGROUND: We investigated mechanical pull-out behavior and tightening torque of
      a novel dual-core pedicle "6T screw" (6T). The aim of this study was to test if
      these changes in screw geometry are increasing the strength of the pedicle screw
      fixation after repeated insertion. METHODS: Three different types of pedicle
      screws were inserted in rigid foam blocks. Tightening torque and pull-out
      strength were measured during two repetitive insertions of a standard 6.5*45-mm
      conical screw. The third insertion into the pilot hole was performed using either
      standard 6.5*45-mm or 7.2*45-mm conical screws or the novel 6.5*45-mm (6T) screw.
      Additionally, we performed a surface analysis to investigate the bone/screw
      interface. RESULTS: The maximal tightening torque at the third insertion of the
      novel 6T screw was 194% higher compared to the standard 6.5*45-mm conical screw
      and 135% higher compared to the standard 7.2*45-mm conical screw. The pull-out
      strength of the 6T screw showed no significant changes, and surface analysis
      revealed a compression of the screw-foam interface due to the different internal
      diameters. CONCLUSIONS: The modified geometrical design of the 6T screw seems to
      have no statistically significant effect on the pull-out strength, although it
      achieved a higher tightening torque. This might be due to the different pitch
      angle cutting a new thread into the material and also to the enlarged inner
      diameter.

PMID- 26200142
TI  - Fracture resistance of simulated immature teeth after different intra-radicular
      treatments.
AB  - The aim of this study was to evaluate the fracture resistance of simulated
      immature teeth after different intra-radicular treatments. Crowns and roots of
      bovine incisors were cut transversally and removed to simulate immature teeth.
      Root canal preparation and flaring were performed using a bur in crown-apex and
      apex-crown direction. The samples were distributed into 5 groups (n=10): Positive
      control (PoC) - no root canal flaring or filling; Negative control (NeC) - teeth
      were sectioned and their root canals were flared; Direct anatomical glass fiber
      post (RaP) - #2 Reforpost main glass fiber post relined with composite resin;
      Double tapered conical glass fiber posts (ExP) - #3 Exacto glass fiber post; and
      #2 Reforpost main glass fiber + Reforpin accessory glass fiber posts (RrP). In
      RaP, ExP and RrP, 4.0-mm apical plugs were done with MTA Angelus. The specimens
      were embedded in polystyrene resin inside cylinders and the periodontal ligament
      was simulated with a polyether-based impression material. The specimens were
      submitted to compressive fracture strength test (0.5 mm/min at 135 degrees 
      relative to the long axis of the tooth) in a servo-hydraulic mechanical testing
      machine MTS 810. Data were subjected to one-way ANOVA and Dunnett's C or Tukey's
      tests (alpha=0.05). The control groups (PoC and NeC) showed lower fracture
      strength than the experimental groups. NeC presented the lowest resistance and
      ExP presented the highest resistance among the experimental groups. The flaring
      procedures produced a detrimental effect on the fracture resistance of the bovine
      teeth. Glass fiber intra-radicular posts increased significantly the fracture
      resistance of simulated immature teeth. 

PMID- 26200143
TI  - Postoperative pain after foraminal instrumentation with a reciprocating system
      and different irrigating solutions.
AB  - The aim of the present study was to evaluate and compare postoperative pain after
      foraminal instrumentation using 5.25% sodium hypochlorite (NaOCl) or 2%
      chlorhexidine (CHX) gel irrigation protocol in nonvital single-rooted teeth after
      reciprocating instrumentation. Sixty-two volunteers presenting a single root
      canal diagnosed with asymptomatic necrosis and apical periodontitis were
      randomized into 2 experimental groups regarding the irrigation protocol (ie,
      5.25% NaOCl and 2% CHX gel groups). Endodontic treatment was performed in a
      single session under reciprocating instrumentation with foraminal
      instrumentation. Volunteers were instructed to record pain intensity. Scores from
      1 to 4 were attributed to each kind of pain after 24, 48, and 72 h. Kolmogorov
      Smirnov and Student's t tests were used to determine significant differences at
      p<0.05. On average, the percentage of patients that had no or mild pain after 24,
      48 or 72 h was 77.4%, 88.7% and 95.1%, respectively. No statistically significant
      age difference was found between the groups (p>0.05, Student's t test).
      Postoperative pain showed no statistically significant difference at any
      observation period when using 5.25% NaOCl or 2% CHX gel (p>0.05). Moreover, no
      significant difference was observed in the mean number of analgesic tablets used
      between the groups (p>0.05). In conclusion, the use of 5.25% NaOCl or 2% CHX gel
      resulted in the same postoperative pain. Therefore, it can be inferred that
      irrigant choice has no relation with short-term follow up regarding postoperative
      pain. 

PMID- 26200144
TI  - Stress generated by customized glass fiber posts and other types by photoelastic
      analysis.
AB  - Endodontic posts are necessary to provide adequate retention and support when no
      sufficient remaining structure is available to retain the core. There are
      different materials and techniques to construct post-and-core, but there is no
      consensus about which one promotes better stress distribution on the remaining
      tooth structure. This study aimed to quantify and evaluate the distribution of
      stress in the root produced by customized glass fiber posts compared to different
      endodontic posts. Twenty-five simulated roots from photoelastic resin were made
      and divided into 5 groups: CPC, cast post-and-core; SP, screw post; CF, carbon
      fiber post; GF, glass fiber post; and CGF, customized glass fiber post. After
      cementing CPC and SP posts with zinc phosphate cement, and CF, GF and CGF posts
      with resin cement, resin cores were made for groups 2-5. Specimens were evaluated
      with vertical or 45 degrees  oblique loading. To analyze the fringes, the root
      was divided into 6 parts: palatal cervical, palatal middle, palatal apical,
      vestibular cervical, vestibular middle, and vestibular apical. The formed fringes
      were photographed and quantified. Data were recorded and subjected to two-way
      ANOVA and Tukey's test (5%). SP (1.95+/-0.60) showed higher stress (p<0.05)
      compared to the others (CPC-0.52+/-0.74; CF-0.50+/-0.75, GF-0.23+/-0.48 and CGF
      0.45+/-0.83). All posts showed high stress in apical third (CPC-1.40+/-0.65; SP
      2.30+/-0.44, CF-1.80+/-0.45, GF-1.20+/-0.45, CGF-1.70+/-1.03) Low stress was
      found in cervical third (CPC-0.20+/-0.45; CF-0.00+/-0.00, GF-0.00+/-0.00, CGF
      0.00+/-0.00), except by SP (1.90+/-0.65), which showed statistical difference
      (p<0.05). Customized post showed high stress concentration at the root and
      conventional glass fiber posts showed more favorable biomechanical behavior. 

PMID- 26200145
TI  - Effect of different irrigating solutions and photo-activated therapy for in vivo
      root canal treatment.
AB  - This study aimed to evaluate histologically the effect of irrigation with 400 ppm
      Sterilox, 2% and 5% sodium hypochlorite (NaOCl), with and without photo-activated
      therapy (PAD), in a single-visit root canal treatment of dog's teeth with apical
      periodontitis (AP). Ten dogs were randomly divided into two groups (n=5): with
      and without PAD, and the root canals into four subgroups, according to the
      irrigating solution: SX (400 ppm Sterilox), SH2 (2% NaOCl), SH5 (5% NaOCl) and SS
      (saline solution) as positive control. A total of 134 root canals were opened and
      left exposed to the oral environment for 14 days and then sealed for 60 days for
      AP induction. Then, root canals were treated according to each proposed
      disinfecting protocol and filled in the same session. After 120 days, the dogs
      were euthanized and the periapical inflammatory events were evaluated under light
      microscopy. Qualitative data were submitted to Kruskal-Wallis and Mann-Whitney
      tests (alpha=0.05). PAD did not produce significant differences in the scores for
      apical inflammation when used after chemo-mechanical preparation (p>0.05). The
      irrigating solutions SX, SH2 and SH5 without PAD were statistically different
      from SS (p<0.05) that presented the greatest scores for apical inflammation. PAD
      did not show any additional effect for the treatment of root canals with pulp
      necrosis and AP in a single visit and 400 ppm Sterilox may be considered an
      alternative to NaOCl in root canal treatment. 

PMID- 26200146
TI  - Effect of pre-treatment with chlorhexidine on the retention of restorations: a
      randomized controlled trial.
AB  - This study aimed to evaluate the effect of chlorhexidine (CHX) application on
      etched dentin on the 6-month retention of restorations placed on non-carious
      cervical lesions (NCCLs). A randomized controlled split-mouth and triple blind
      trial was carried out. Patients (n=42) with at least two non-carious cervical
      lesions were included. NCCLs were randomly assigned to two groups: control
      (placebo solution) or test group (2% CHX solution for 60 s after acid etching and
      before the adhesive application). Class V restorations (n=169) were performed
      with an etch-and-rinse adhesive system and composite resin by 10 trained
      operators. A calibrated examiner evaluated the restorations at 1 week (baseline)
      and at 6 months using the FDI criteria. The primary outcome was retention of the
      restorations. The analysis of factors associated to failure of restorations was
      carried out by Fisher's exact test (alpha=0.05). After 6 months of follow-up,
      3.4% (CI 95% 1.3-7.3) of the restorations failed. There was no statistically
      significant difference between control and CHX (p=0.920). Regarding the cavity
      variables, deeper (p=0.04), wider (p=0.004) and wedge-shaped (p=0.033) cavities
      failed more. Both treatments provided acceptable clinical performance of the
      restorations. The use of CHX as a adjuvant in dentin adhesion did not influence
      the retention of Class V restorations after 6 months of follow-up. 

PMID- 26200147
TI  - Response of human pulps to different in-office bleaching techniques: preliminary
      findings.
AB  - This study evaluated a whitening effect and the likely side effect (tooth
      sensitivity and pulp response) of human teeth subjected to different in-office
      bleaching (IOB) techniques and materials, mainly the presence of calcium in the
      IOB materials. A calcium-free (CF) and a calcium-containing (CC) 35% hydrogen
      peroxide (HP) gels were evaluated. The CF was refreshed every 15 minutes, three
      times (CF 3-15) or in a single 45-min application (CF 1-45) at one bleaching
      appointment. The CC was used only in a single 45-min application (CC 1-45). Each
      technique was applied in 5 mandibular incisors scheduled for extraction for
      different patients. In control group, no tooth bleaching was performed. The tooth
      colour (TC) and tooth sensitivity (TS) were recorded at baseline and after IOB.
      The teeth were extracted 2 days after the application of IOB and subjected to
      histological analysis. The data was submitted to appropriate statistical analysis
      (alpha=0.05). The changes of TC were similar between groups and statistically
      different from the control (p<0.05). However, TS of groups bleached with CF was
      statistically higher than that recorded for CC and the control (p<0.05). In CF 3
      15 and CF 1-45 groups, the coronal pulp tissue exhibited partial necrosis
      associated with tertiary dentin deposition. In CC 1-45 group smaller area of
      necrosis occurred only in three bleached teeth in which tertiary dentin
      deposition was observed. The calcium-containing 35%HP gel could be preferable for
      in-office bleaching because it caused less tooth sensibility and pulp damage. 

PMID- 26200148
TI  - Does the presence of sucrose in pediatric antibiotics influence the enamel
      mineral loss and the Streptococcus mutans counts in dental biofilm?
AB  - The role of antibiotics containing sucrose on the formation of dental caries is
      still controversial. This study aimed to investigate the effect of two
      antibiotics (amoxicillin and potassium clavulanate suspension), with and without
      sucrose, on human dental hardness and Streptococcus mutans counts in dental
      biofilm. Primary tooth fragments (n=72) were coated with nail varnish leaving a
      window of 2.25 mm diameter. Specimens were fixed in 24-well polystyrene plates,
      containing BHI medium. S. mutans (clinical strains) represented the inoculum to
      form biofilm on the fragments for 24 h. Twelve fragments were separated for the
      initial count of microorganisms (baseline). The other fragments were divided into
      4 groups (n=12) of treatment: G1 (Clavulin(r)), G2 (Betamox(r)), G3
      (chlorhexidine 0.12%), G4 (sucrose 10%). All specimens had their self-control
      area (covered area). The cross-sectional microhardness (CSMH) was evaluated for
      each specimen. All the treated groups had a loss of hardness compared to their
      self-controls (p<0.05). Both drugs inhibited the S. mutans growth and promoted no
      CSMH difference among them. Both antibiotics eliminated all formed biofilm and
      did not cause mineral loss from the enamel, regardless the presence of sucrose in
      its formulation. 

PMID- 26200149
TI  - Load-application devices: a comparative strain gauge analysis.
AB  - In view of the low loading values commonly employed in dentistry, a load
      application device (LAD) was developed as option to the universal testing machine
      (UTM), using strain gauge analysis. The aim of this study was to develop a load
      application device (LAD) and compare the LAD with the UTM apparatus under axial
      and non-axial loads. An external hexagonal implant was inserted into a
      polyurethane block and one EsthetiCone abutment was connected to the implant. A
      plastic prosthetic cylinder was screwed onto the abutment and a conical pattern
      crown was fabricated using acrylic resin. An impression was made and ten
      identical standard acrylic resin patterns were obtained from the crown
      impression, which were cast in nickel-chromium alloy (n=10). Four strain gauges
      were bonded diametrically around the implant. The specimens were subjected to
      central (C) and lateral (L) axial loads of 30 kgf, on both devices: G1: LAD/C;
      G2: LAD/L; G3: UTM/C; G4: UTM/L. The data (MUepsilon) were statistically analyzed
      by repeated measures ANOVA and Tukey's test (p<0.05). No statistically
      significant difference was found between the UTM and LAD devices, regardless of
      the type of load. It was concluded that the LAD is a reliable alternative, which
      induces microstrains to implants similar to those obtained with the UTM. 

PMID- 26200150
TI  - Supplementation of an orange juice with dietary proteins to prevent enamel and
      dentin erosion.
AB  - Protein supplementation may be an alternative to reduce the erosive potential of
      acidic drinks. The aim of this in vitro study was to evaluate the erosive
      potential of an orange juice modified by dietary proteins. A commercially
      available orange juice was added 0.2 g/L casein, 2.0 g/L ovalbumin and their
      combination. The juice with no additives and a commercially available calcium
      modified juice were used as negative and positive controls, respectively. Human
      enamel and dentin specimens (n=11) were tested in an erosion-remineralization
      cycling model. Enamel was analyzed by surface microhardness and profilometry,
      whilst dentin by profilometry only. Statistical analyses were performed using one
      way ANOVA followed by Tukey's test (p<0.05). Calcium-modified juice showed the
      lowest erosive potential for both analyses (p<0.05). For enamel, the protein
      added groups did not differ from each other (p>0.05) and showed significantly
      lower enamel loss compared to negative control (p<0.05). Regarding surface
      microhardness, casein showed the highest values compared to negative control
      (p<0.05). For dentin, none of the protein-added groups showed lower values of
      surface loss compared to negative control (p>0.05). In conclusion, for enamel the
      protein-modified orange juices presented reduced erosion of enamel, with casein
      showing a trend for better protection. For dentin, no reduction in the erosive
      potential was observed for the tested protein-modified orange juices. 

PMID- 26200151
TI  - Surface roughness of composite resins subjected to hydrochloric acid.
AB  - The purpose of this study was to determine the influence of hydrochloric acid on
      surface roughness of composite resins subjected to brushing. Sixty samples
      measuring 2 mm thick x 6 mm diameter were prepared and used as experimental
      units. The study presented a 3x2 factorial design, in which the factors were
      composite resin (n=20), at 3 levels: microhybrid composite (Z100), nanofilled
      composite (FiltekTM Supreme), nanohybrid composite (Ice), and acid challenge
      (n=10) at 2 levels: absence and presence. Acid challenge was performed by
      immersion of specimens in hydrochloric acid (pH 1.2) for 1 min, 4 times per day
      for 7 days. The specimens not subjected to acid challenge were stored in 15 mL of
      artificial saliva at 37 oC. Afterwards, all specimens were submitted to abrasive
      challenge by a brushing cycle performed with a 200 g weight at a speed of 356
      rpm, totaling 17.8 cycles. Surface roughness measurements (Ra) were performed and
      analyzed by ANOVA and Tukey test (p<=0.05). Surface roughness values were higher
      in the presence (1.07+/-0.24) as compared with the absence of hydrochloric acid
      (0.72+/-0.04). Surface roughness values were higher for microhybrid (1.01+/-0.27)
      compared with nanofilled (0.68 +/-0.09) and nanohybrid (0.48+/-0.15) composites
      when the specimens were not subjects to acid challenge. In the presence of
      hydrochloric acid, microhybrid (1.26+/-0.28) and nanofilled (1.18+/-0,30)
      composites presents higher surface roughness values compared with nanohybrid
      (0.77+/-0.15). The hydrochloric acid affected the surface roughness of composite
      resin subjected to brushing. 

PMID- 26200152
TI  - Effect of low shrinkage monomers on physicochemical properties of dental resin
      composites.
AB  - The aim of this study was to evaluate the effect of low shrinkage monomers on
      physicochemical properties of dental resin composites. Two low shrinkage resin
      composites: one with a crosslink branching monomer (Kalore, GC Corp) and a novel
      monomer (Venus Diamond, Heraeus Kulzer) were compared to a conventional resin
      composite formulation (Filtek Z250, 3M/ESPE). The volumetric shrinkage was
      evaluated by uCT analysis (n=5) and the physicochemical properties by degree of
      C=C conversion (DC), flexural strength (FS) and Young's modulus (YM) (n=10). All
      samples were light cured by a LED device (Radii, SDI) with 16 J/cm2. The results
      were analysed by one-way ANOVA and Tukey test for multiple comparisons
      (alpha=0.05). No statistical difference was found between uCT shrinkage values to
      Kalore (1.8%) and Venus Diamond (1.7%) (p>=0.05); Z250 presented statistical
      highest shrinkage value (2.0%). Kalore presented higher statistical DC (60.8%)
      than Venus Diamond (49.5%) and Z250 (49.6%). No statistical difference was found
      between FS or YM properties to Venus Diamond and Z250; Kalore presented
      statistical lowest FS and YM properties (p>=0.05). CONCLUSION: Using novel
      monomers seem to reduce polymerization shrinkage without affecting the
      physicochemical properties evaluated of resin composites rather than using
      crosslink branching monomers.

PMID- 26200153
TI  - Passivity of conventional and CAD/CAM fabricated implant frameworks.
AB  - The objective of this research was to evaluate the passivity by measuring the
      passive fit and strain development of frameworks screwed on abutments, made by
      CAD/CAM technology, and to compare these parts with samples manufactured by
      conventional casting. Using CAD/CAM technology, four samples were made from
      zirconia (Zircad) and four samples were manufactured from cobalt-chrome
      (CoCrcad). The control groups were four specimens of cobalt-chrome, made by one
      piece casting (CoCrci), with a total of 12 frameworks. To evaluate the passive
      fit, the vertical misfit at the abutment-framework interface was measured with
      scanning electron microscopy (250*) when only one screw was tightened. The mean
      strain in these frameworks was analyzed by photoelasticity test. A significant
      difference in the passive fit was observed between the control and sample groups.
      CoCrcad exhibited the best value of passive fit (48.76+/-13.45 um) and CoCrci the
      worst (187.55+/-103.63 um); Zircad presented an intermediate value (103.81+/
      43.15 um). When compared to the other groups, CoCrci showed the highest average
      stress around the implants (17.19+/-7.22 kPa). It was concluded that CAD/CAM
      fabricated frameworks exhibited better passivity compared with conventionally
      fabricated frameworks. CAD/CAM-fabricated Co-Cr frameworks may exhibit better
      passive fit compared with CAD/CAM-fabricated zirconia frameworks. Even so,
      similar levels of stress were achieved for CAD/CAM-fabricated frameworks. 

PMID- 26200154
TI  - Effect of mechanical cycling on screw torque in external hexagon implants with
      and without platform switching.
AB  - This in vitro study evaluated the effect of mechanical cycling on the torque of
      retaining screw in external hexagon implants with platform switching (PS),
      regular platform (RP) and wide platform (WP). A total of 30 specimens were
      equally divided into 3 groups: PS, PR and WP. Each specimen was prepared with
      implants: 3.75 x 10 mm for RP group and 5.0x10 mm for PS and WP groups and its
      respective abutment with 32 Ncm torque. All groups were subjected to 106 cycles
      with 100 N (corresponding to about 40 months of chewing). The results were
      obtained with the reverse torque of each specimen and data were evaluated using
      ANOVA and Tukey test (p<0.05). The PS group showed statistically significant
      difference in screw removal torque (30.06+/-5.42) compared with RP (23.75+/-2.76)
      and WP (21.32+/-3.53) (p<0.05) groups; the RP and WP groups showed no
      statistically significant difference between them. It was concluded that the PS
      group showed higher reverse torque value, suggesting lower susceptibility of the
      abutment screw loosening. 

PMID- 26200155
TI  - New methodology to evaluate bond strength of root-end filling materials.
AB  - This study evaluated the bond strength of root-end filling materials to root-end
      cavities using a new methodology. Twenty maxillary central incisors were
      subjected to biomechanical preparation (#80 hand file) and sectioned
      transversally 2 mm short of the apex and 4 mm coronally to this point. The root
      cylinders were embedded in acrylic resin and positioned at 45 degrees  to the
      horizontal plane for preparation of root-end cavities with a diamond ultrasonic
      retrotip. Two groups (n=10) were formed according to the root-end filling
      material: MTA and Super EBA. A gutta-percha cone (#80) was tug-backed at the
      limit between the canal and the root-end cavity. The cavity was filled and the
      gutta-percha cone was removed after complete setting of the sealer. The specimens
      were placed in an Instron machine with the root-end filling turned downwards. The
      push-out shaft was inserted in the space previously occupied by the gutta-percha
      cone and run at a crosshead speed of 1.0 mm/min for pushing out the root-end
      filling material. Data were analyzed by ANOVA (alpha=5%). Super EBA (6.03+/-1.31)
      presented higher bond strength (MPa) than MTA (1.81+/-0.45) (p>0.05). There was a
      predominance of cohesive failures for Super EBA and mixed for MTA. The protocol
      of specimen preparation is effective and introduces a specific methodology for
      assessing bond strength of root-end filling materials to dentin. Among the
      materials, Super EBA presented the highest bond strength. 

PMID- 26200156
TI  - Adverse effects on PMMA caused by mechanical and combined methods of denture
      cleansing.
AB  - This study evaluated the abrasiveness of mechanical and combined methods of
      denture hygiene, by the analysis of mass loss and surface roughness. Acrylic
      resin specimens (Plexiglass) were brushed by a tooth brushing machine (Mavtec)
      with a soft brush (Tek) and water (control) or four dentifrices (Sorriso,
      Colgate, Polident and Corega) (Experimental groups) for 50 min, representing one
      year of brushing (mechanical method). After brushing, the specimens were immersed
      in 0.5% sodium hypochlorite simulating a daily cleaning of 20 min for one year
      (combined method). Distilled water (23 oC) was employed as control. The mass loss
      (g) was analyzed by an analytical balance and the surface roughness (MUm) by a
      rugosimeter. Data were subjected to ANOVA and Bonferroni test (alpha=0.05).
      Polident dentifrice showed lowest values of mass loss for both methods
      (mechanical: -0.0072+/-0.0017, combined:-0.011+/-0.002) and the combined method
      resulted in greater mass loss than the mechanical, except for Corega. For the
      surface roughness, after the mechanical method, the lowest values were registered
      for water (-0.007+/-0.016) and Polident (0.402+/-0.378); for the combined method,
      water (-0.063+/-0.013) showed the lowest values; there was no statistically
      significant difference between methods. It was concluded that Polident was the
      less abrasive dentifrice and the association between chemical and mechanical
      methods increased the mass loss but did not change the surface roughness of
      specimens. 

PMID- 26200157
TI  - Three-dimensional digital evaluation of dental arches in infants with cleft lip
      and/or palate.
AB  - The aim of this study was to measure and compare the dimensions of the dental
      arches on three-dimensional digital study models in children with and without
      cleft lip and palate before the primary surgery. The sample consisted of 223
      digital models of children aged 3-9 months, divided into 5 groups: without
      craniofacial deformities, unilateral and bilateral incomplete cleft lip and
      alveolus, unilateral and bilateral complete cleft lip and alveolus, unilateral
      cleft lip and palate, and bilateral cleft lip and palate. Dental casts of the
      maxillary dental arches of the children were used. The dental casts underwent a
      process of scanning through 3D scanner and the measurements used for the
      correlation among groups were made on the scanned images. Statistical analysis
      was performed by t test and ANOVA followed by Tukey test. The results showed that
      the intercanine distance and anterior cleft width was wider in children with
      unilateral cleft lip and palate. The intertuberosity distances and posterior
      cleft width was wider in children with bilateral cleft lip and palate among the
      groups. Children with cleft lip and palate before the primary surgery had wider
      maxillary arch dimensions than the children without cleft lip and palate. 

PMID- 26200158
TI  - Stress and anxiety in children after the use of computerized dental anesthesia.
AB  - The aim of this study was to evaluate the transitory stress levels and the
      anxiety state in children submitted to conventional and computerized dental
      anesthesia. Twenty children (7 to 12 years) were randomly assigned to receive
      conventional and computerized dental anesthesia. To investigate the hypothesis
      that transitory stress could be lower after using computerized anesthesia
      compared to conventional anesthesia, cortisol levels in saliva were measured
      before and after each technique. Anxiety was also evaluated individually by
      answering the State-Trait Anxiety Inventory for Children (STAIC). Numerical data
      were analyzed statistically by the Mann-Whitney non-parametric test (5%
      significance level). Salivary cortisol levels increased in 8 (40%) patients after
      conventional anesthesia and in 9 (45%) patients after computerized anesthesia,
      with no statistically significant difference between the two types (p=0.34). In
      the same way, no statistically significant difference was found between the
      techniques (p=0.39) related to the psychological analysis based on the STAIC
      scores. Local anesthesia using either conventional anesthesia or a computerized
      delivery system produced similar level of stress/anxiety in pediatric patients,
      using both quantitative and qualitative analyses. 

PMID- 26200159
TI  - Replantation as treatment for extrusive luxation.
AB  - In the treatment of extrusive luxation cases, it is important that the
      repositioning of extruded tooth in the socket is done as soon as possible. If
      this does not occur, periapical clot becomes organized and makes replantation
      difficult reposition. In this article the patient referred to the Clinics for
      dental trauma sustaining extrusive luxation of the maxillary right central
      incisor. The patient reported having suffered a bicycle accident 12 days before,
      which caused traumatic tooth injuries. The repositioning was attempted without
      success and an alternative form of treatment was necessary to solve the case.
      Intentional tooth replantation, which is the deliberate extraction of the tooth
      and its replantation, was indicated. This technique allows clot removal and
      correct repositioning of the extruded tooth. Care should be taken as endodontic
      treatment is required for the prevention of subsequent infection-related
      resorption. Intracanal dressing with calcium hydroxide was used for 30 days
      before final root filling. Splint, systemic antibiotics and avoidance of further
      damage to the root surface is also important. After 49 months, showed clinical
      and radiographic characteristics of normality and demonstrates the availability
      of this technique to adversity in trauma. 

PMID- 26200160
TI  - Oral findings and dental treatment in a child with Williams-Beuren syndrome.
AB  - Williams-Beuren syndrome (WBS), also known as Williams syndrome, is a rare
      congenital disorder involving cardiovascular problems, mental retardation,
      distinctive facial features and tooth anomalies. It is caused by the
      submicroscopic deletion of 1.5 to 1.8 Mb on chromosome 7q11.23. This paper
      reports the dental care to a 7-year-old child with WBS syndrome. The interview
      also revealed visual impairment, sensorineural hearing loss, hyperacusis,
      photophobia and hoarse voice. The intraoral clinical examination showed anterior
      open bite, tongue thrusting, excessive interdental spacing, enamel
      hypomineralization of the incisors, hypoplasia and caries lesions. The dental
      treatment included: modulating sessions to control aversion to noises, the
      photophobia, and the dental fear and anxiety because of his reduced visual
      acuity; oral hygiene instructions, dietary and daily use of a 0.05% sodium
      fluoride mouthwash; the permanent mandibular left first molar was treated
      endodontically, and maxillary and mandibular first molars were restored with
      amalgam. Due to the patient's heart defect, a prophylactic antibiotic regimen was
      prescribed prior to the dental procedures. This patient has been followed up for
      4 years and this case report underscores the importance of early dental
      evaluation and counseling for parents of WBS patients. 

PMID- 26200161
TI  - Surgical treatment of bisphosphonate-related osteonecrosis of the jaws with the
      use of buccal fat pad: case report.
AB  - Bisphosphonate-related osteonecrosis of the jaws (BROJ) has been described since
      2003 as an adverse effect of bisphosphonate medications. These drugs act on the
      vasculature and bone remodeling, mainly on osteoclastic activity and can cause
      areas of necrotic bone exposure. Treatment for the BROJ is not yet defined, but
      surgical treatment is one of the forms proposed, which may cause oral deformities
      like sinus communication in some cases. In situations like this the buccal fat
      pad is an important alternative for coating nasal-oral communications, due its
      large blood supply, elasticity, absence of restriction by age and safety. This
      paper presents the case of a 58-year-old woman with BROJ in the left maxilla
      caused by the use of zoledronic acid for metastatic breast cancer. The extensive
      necrotic bone area was surgically removed resulting in oral sinus communication.
      A buccal fat pad was used to cover the defect. More studies should be performed
      regarding the treatment of BROJ but, if necessary, a buccal fat pad flap could be
      an alternative to solve nasal-oral communications related to BROJ. 

PMID- 26200162
TI  - Cone-Beam Computed Tomography: Beyond Diagnostics.

PMID- 26200163
TI  - Association of Keratinized Mucosa and Periimplant Soft Tissue Stability Around
      Implants With Platform Switching.
AB  - PURPOSE: To investigate the influence of the width of keratinized mucosa (KM) on
      clinical parameters around dental implants with platform switching. METHODS: One
      hundred eighteen patients with 320 implants participated in the evaluation. The
      width of KM, modified sulcus bleeding index (mBI), plaque index (PLI), mucosal
      recession (MR), and the compliance to the implant maintenance therapy (IMT) were
      evaluated. RESULTS: A wide band of KM (KM width >= 2 mm) was associated with a
      significant lower mBI (0.12 +/- 0.37; P < 0.0001), PLI (0.45 +/- 0.56; P =
      0.001), and less MR (0.06 +/- 0.23; P < 0.0001) than a narrow band of KM (KM
      width < 2 mm) (Papilla Bleeding Index [PBI], 0.39 +/- 0.60; PLI, 0.69 +/- 0.63;
      MR, 0.27 +/- 0.44). By "regular" and "irregular" IMT, a statistically significant
      difference was found between wide and narrow width of KM, for the mBI (wide vs
      narrow; 0.11 +/- 0.31 vs 0.31 +/- 0.52, P = 0.004 and 0.14 +/- 0.45 vs 0.49 +/-
      0.69, P = 0.002, respectively). CONCLUSION: Absence of keratinized mucosa was
      associated with significant higher PLI, mBI, and MR. The IMT does not reject the
      protective role of KM against inflammation.

PMID- 26200164
TI  - Do Porous Titanium Granule Grafts Affect Bone Microarchitecture at Augmented
      Maxillary Sinus Sites? A Pilot Split-Mouth Human Study.
AB  - BACKGROUND: The aim of this randomized controlled clinical study was to analyze
      the bone microarchitecture at augmented maxillary sinus sites by using different
      materials in patients to compare the effect of porous titanium granules as a
      sinus augmentation material with bone microstructural features. MATERIALS AND
      METHODS: Eight subjects with bilateral atrophic posterior maxilla of residual
      bone height <4 mm included in this study and each patient was treated with
      bilateral sinus augmentation procedure using xenograft with equine origin
      (Apatos, Osteobiol; Tecnoss Dental) and xenograft (1 g) + porous titanium (1 g)
      granules (Natix; Tigran Technologies AB). Sixteen human bone biopsy samples were
      taken from patients receiving two-stage sinus augmentation therapy during implant
      installation and analyzed using microcomputerized tomography. Three-dimensional
      bone structural parameters were analyzed in details: tissue volume, bone volume,
      percentage of bone volume, bone surface and bone surface density, bone specific
      surface, trabecular thickness trabecular separation, trabecular number,
      trabecular pattern factor, structural model index, fractal dimension, and bone
      mineral density. RESULTS: No statistically significant differences were found
      between groups according to bone structural parameters. CONCLUSIONS: Porous
      titanium grafts may ensure a space for new bone formation in the granules, which
      may be a clinical advantage for long-term success.

PMID- 26200165
TI  - Palladium Catalyzed C-Arylation of Amino Acid Derived Hydantoins.
AB  - Palladium(II) trifluoroacetate (5 mol %) catalyzes the C-arylation of N,N
      disubstituted hydantoins by aryl iodides in good yield. The reaction proceeds
      through base-promoted enolization of the amino acid derived hydantoins, and the
      resulting 5,5-disubstituted hydantoins may be deprotected at one or both N atoms
      to yield biologically active structures or alternatively hydrolyzed to the parent
      alpha-aryl alpha-amino acids. The reaction is successful with a variety of parent
      amino acids and a range of electron-rich and electron-poor aryl iodides. 

PMID- 26200169
TI  - International Association for Suicide Prevention.

PMID- 26200167
TI  - In Silico Prediction of Cytochrome P450-Mediated Biotransformations of
      Xenobiotics: A Case Study of Epoxidation.
AB  - Predicting the biotransformation of xenobiotics is important in toxicology;
      however, as more compounds are synthesized than can be investigated
      experimentally, powerful computational methods are urgently needed to prescreen
      potentially useful candidates. Cytochrome P450 enzymes (P450s) are the major
      enzymes involved in xenobiotic metabolism, and many substances are bioactivated
      by P450s to form active compounds. An example is the conversion of olefinic
      substrates to epoxides, which are intermediates in the metabolic activation of
      many known or suspected carcinogens. We have calculated the activation energies
      for epoxidation by the active species of P450 enzymes (an iron-oxo porphyrin
      cation radical oxidant, compound I) for a diverse set of 36 olefinic substrates
      with state-of-the-art density functional theory (DFT) methods. Activation
      energies can be estimated by the computationally less demanding method of
      calculating the ionization potentials of the substrates, which provides a useful
      and simple predictive model based on the reaction mechanism; however, the
      preclassification of these diverse substrates into weakly polar and strongly
      polar groups is a prerequisite for the construction of specific predictive models
      with good predictability for P450 epoxidation. This approach has been supported
      by both internal and external validations. Furthermore, the relation between the
      activation energies for the regioselective epoxidation and hydroxylation
      reactions of P450s and experimental data has been investigated. The results show
      that the computational method used in this work, single-point energy calculations
      with the B3LYP functional including zero-point energy and solvation and
      dispersion corrections based on B3LYP-optimized geometries, performs well in
      reproducing the experimental trends of the epoxidation and hydroxylation
      reactions. 

PMID- 26200166
TI  - A Multicenter Randomized Trial of Continuous versus Intermittent beta-Lactam
      Infusion in Severe Sepsis.
AB  - RATIONALE: Continuous infusion of beta-lactam antibiotics may improve outcomes
      because of time-dependent antibacterial activity compared with intermittent
      dosing. OBJECTIVES: To evaluate the efficacy of continuous versus intermittent
      infusion in patients with severe sepsis. METHODS: We conducted a randomized
      controlled trial in 25 intensive care units (ICUs). Participants commenced on
      piperacillin-tazobactam, ticarcillin-clavulanate, or meropenem were randomized to
      receive the prescribed antibiotic via continuous or 30-minute intermittent
      infusion for the remainder of the treatment course or until ICU discharge. The
      primary outcome was the number of alive ICU-free days at Day 28. Secondary
      outcomes were 90-day survival, clinical cure 14 days post antibiotic cessation,
      alive organ failure-free days at Day 14, and duration of bacteremia. MEASUREMENTS
      AND MAIN RESULTS: We enrolled 432 eligible participants with a median age of 64
      years and an Acute Physiology and Chronic Health Evaluation II score of 20. There
      was no difference in ICU-free days: 18 days (interquartile range, 2-24) and 20
      days (interquartile range, 3-24) in the continuous and intermittent groups (P =
      0.38). There was no difference in 90-day survival: 74.3% (156 of 210) and 72.5%
      (158 of 218); hazard ratio, 0.91 (95% confidence interval, 0.63-1.31; P = 0.61).
      Clinical cure was 52.4% (111 of 212) and 49.5% (109 of 220); odds ratio, 1.12
      (95% confidence interval, 0.77-1.63; P = 0.56). There was no difference in organ
      failure-free days (6 d; P = 0.27) and duration of bacteremia (0 d; P = 0.24).
      CONCLUSIONS: In critically ill patients with severe sepsis, there was no
      difference in outcomes between beta-lactam antibiotic administration by
      continuous and intermittent infusion. Australian New Zealand Clinical Trials
      Registry number (ACT RN12612000138886).

PMID- 26200171
TI  - Increased water intake to reduce headache: learning from a critical appraisal.
AB  - CLINICAL BOTTOM LINE: Water intake is a cost effective, non-invasive and low-risk
      intervention to reduce or prevent headache pain. RATIONALE: Chronic mild
      dehydration may trigger headache. Increased water intake could help. A small
      trial shows modest benefit; however, a larger methodologically sound randomized
      controlled trial is needed to confirm efficacy. CRITICALLY APPRAISED PAPER:
      Spigt, M., Weerkamp, N., Troost, J., van Schayck, C. P., & Knottnerus, J. A.
      (2012). 'A randomized trial on the effects of regular water intake in patients
      with recurrent headaches.' Family practice, 29(4), 370-5. Doi:
      10.1093/fampra/cmr112 CLINICAL SCENARIO: Patients from primary care registered as
      'headache', 'tension headache' and/or 'migraine' for more than one year who
      suffer at least two episodes of moderately intense headache or more than four
      mildly intense episodes of headache per month with a daily fluid intake of less
      than 2.5 litres per day. PICO (M): Patient/Problem = Headache > 1 year with 2
      moderately intense or 4 mildly intense episodes per month Intervention = 1.5
      litres water per day + stress control and sleep hygiene Comparison/Control =
      stress control and sleep hygiene Outcome = Reduce or eliminate headache
      Methodology = Therapy RCT Table 1: Final Search Terms TRIP Data Base: hits = 517
      used filter Extended Primary research 4 found 1 paper applicable 'Water intake
      '[MeSH Terms] AND 'Headache '[All Fields]' Best match to PICO, (2012) RCT
      SELECTION CRITERION AND OVERALL RESULTS: 102 headache patients in16 primary care
      clinics were randomized into control (n = 50) and intervention groups (n = 52)
      Inclusion criteria = two > episodes of moderately intense headache or five >
      mildly intense headaches per month and total fluid intake > 2.5 litres per day,
      Follow-up @ 3 months. 79% intervention and 66% of controls completed RCT.
      Drinking more water resulted in a statistically significant improvement of 4.5
      (confidence interval: 1.3-7.8) points on Migraine-Specific Quality of Life
      (MSQOL). 47% in the intervention (water) group self-reported improvement (6 > on
      a 10-point scale) against 25% in controls. Drinking water did not reduce headache
      days. COMMENTS: The transparency from the author of this critically appraised
      paper enables others to use this study as a teaching tool and to learn from the
      shortcomings in the trial. The study was underpowered and contains methodological
      shortcomings. Participants were partially un-blinded during the trial increasing
      the risk for bias. Only the subjective measures are statistically significant and
      attrition was significant. The intervention is low risk and of negligible cost. A
      methodologically sound RCT is recommended to evaluate if the intervention has
      beneficial effects.

PMID- 26200170
TI  - Neuroprotective Effects of the Glutamate Transporter Activator (R)-(-)-5-methyl-1
      nicotinoyl-2-pyrazoline (MS-153) following Traumatic Brain Injury in the Adult
      Rat.
AB  - Traumatic brain injury (TBI) in humans and in animals leads to an acute and
      sustained increase in tissue glutamate concentrations within the brain,
      triggering glutamate-mediated excitotoxicity. Excitatory amino acid transporters
      (EAATs) are responsible for maintaining extracellular central nervous system
      glutamate concentrations below neurotoxic levels. Our results demonstrate that as
      early as 5 min and up to 2 h following brain trauma in brain-injured rats, the
      activity (Vmax) of EAAT2 in the cortex and the hippocampus was significantly
      decreased, compared with sham-injured animals. The affinity for glutamate (KM)
      and the expression of glutamate transporter 1 (GLT-1) and glutamate aspartate
      transporter (GLAST) were not altered by the injury. Administration of (R)-(-)-5
      methyl-1-nicotinoyl-2-pyrazoline (MS-153), a GLT-1 activator, beginning
      immediately after injury and continuing for 24 h, significantly decreased
      neurodegeneration, loss of microtubule-associated protein 2 and NeuN (+)
      immunoreactivities, and attenuated calpain activation in both the cortex and the
      hippocampus at 24 h after the injury; the reduction in neurodegeneration remained
      evident up to 14 days post-injury. In synaptosomal uptake assays, MS-153 up
      regulated GLT-1 activity in the naive rat brain but did not reverse the reduced
      activity of GLT-1 in traumatically-injured brains. This study demonstrates that
      administration of MS-153 in the acute post-traumatic period provides acute and
      long-term neuroprotection for TBI and suggests that the neuroprotective effects
      of MS-153 are related to mechanisms other than GLT-1 activation, such as the
      inhibition of voltage-gated calcium channels.

PMID- 26200172
TI  - Can biofeedback training of psychophysiological responses enhance athletes' sport
      performance? A practitioner's perspective.
AB  - BACKGROUND: In recent years, biofeedback has become increasingly popular for its
      proven success in peak performance training - the psychophysiological preparation
      of athletes for high-stakes sport competitions, such as the Olympic games. The
      aim of this research was to test whether an 8-week period of exposure to
      biofeedback training could improve the psychophysiological control over
      competitive anxiety and enhance athletic performance in participating subjects.
      METHODS: Participants of this study were highly competent athletes, each training
      in different sport disciplines. The experimental group consisted of 18 athletes
      (4 women, 14 men), whereas the Control group had 21 athletes (4 women, 17 men).
      All athletes were between 16 and 34 years old. The biofeedback device, Nexus 10,
      was used to detect and measure the psychophysiological responses of athletes.
      Athletes from both groups (control and experimental) were subjected to stress
      tests at the beginning of the study and once again at its conclusion. In between,
      the experimental group received training in biofeedback techniques. We then
      calculated the overall percentage of athletes in the experimental group compared
      with those in the control group who were able to control respiration, skin
      conductance, heart rate, blood flow amplitude, heart rate variability, and heart
      respiration coherence. One year following completion of the initial study, we
      questioned athletes from the experimental group, to determine whether they
      continued to use these skills and if they could detect any subsequent enhancement
      in their athletic performance. RESULTS: We demonstrated that a greater number of
      participants in the experimental group were able to successfully control their
      psychophysiological parameters, in comparison to their peers in the control
      group. Significant results (p < 0.05) were noted in regulation of GSR following
      short stress test conditions (p = 0.037), in regulation of HR after exposure to
      STROOP stressor (p = 0.037), in regulation of GSR following the Math and GSR
      stressors (p = 0.033, p = 0.409) and in achieving HR - breathing coherence
      following the math stressor (p = 0.042). CONCLUSION: One year following
      completion of the training program, all participants from the experimental group
      indicated that they were still using the biofeedback - psycho-regulation skills.
      Furthermore, these participants uniformly reported believing that these skills
      had enhanced their athletic performance and general well-being.

PMID- 26200173
TI  - Surveillance of the Activity of Aminoglycosides and Fluoroquinolones Against
      Ophthalmic Pathogens from Europe in 2010-2011.
AB  - PURPOSE/AIM: Bacterial infections of the ocular surface are commonly treated
      empirically with broad spectrum antibiotics. Due to concerns over increasing
      antibiotic resistance, we evaluated current susceptibility patterns of the ocular
      bacterial pathogens in Europe. MATERIALS AND METHODS: Non-consecutive ocular
      isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS),
      Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa were
      collected in 2011 from centers in France, Germany, Italy, Poland, Slovak
      Republic, Spain, and the United Kingdom. Centers were asked to provide similar
      numbers of methicillin-susceptible and -resistant staphylococcal isolates.
      Minimum inhibitory concentrations were determined for fluoroquinolones
      (besifloxacin, ciprofloxacin, moxifloxacin), aminoglycosides (tobramycin,
      gentamicin, netilmicin), oxacillin, chloramphenicol and erythromycin. Isolates
      were categorized as susceptible, intermediate, or resistant according to European
      Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. RESULTS: A
      total of 741 ocular isolates were obtained. Antibiotic resistance rates depended
      not only on the antibiotic and species, but also varied greatly by the country of
      origin. Resistance to ciprofloxacin, tobramycin, erythromycin, and to a lesser
      extent, chloramphenicol, was a concern for all staphylococci. Multidrug
      resistance was common among methicillin-resistant S. aureus (MRSA) and MRCoNS and
      isolates of S. pneumoniae, H. influenzae, and P. aeruginosa were frequently non
      susceptible to erythromycin, beta-lactams, and ciprofloxacin/tobramycin,
      respectively. Resistance rates showed substantial differences among the seven
      countries tested. Fluoroquinolones and aminoglycosides showed differences in
      antibacterial potency and resilience toward the antibiotic resistance mechanisms.
      CONCLUSIONS: Methicillin-resistant staphylococcal isolates were frequently non
      susceptible to a multitude of other antibiotics, making MRSA and MRCoNS a
      potentially significant concern. The broad range of resistance rates observed
      across Europe in this study confirms the importance of considering current local
      resistance patterns when antibacterial agents are chosen for empiric management
      of ocular infections.

PMID- 26200174
TI  - Canakinumab efficacy in refractory adult-onset PFAPA syndrome.

PMID- 26200175
TI  - Effect of Calcium Channel Blockade on Vismodegib-Induced Muscle Cramps.

PMID- 26200176
TI  - The Importance of Validation Studies in Perioperative Database Research.

PMID- 26200177
TI  - Happy 53rd Birthday GIK: Insulin, Cake, and Presents.

PMID- 26200178
TI  - Identifying Obstructive Sleep Apnea in Administrative Data: A Study of Diagnostic
      Accuracy.
AB  - BACKGROUND: Health administrative (HA) databases are increasingly used to
      identify surgical patients with obstructive sleep apnea (OSA) for research
      purposes, primarily using diagnostic codes. Such means to identify patients with
      OSA are not validated. The authors determined the accuracy of case-ascertainment
      algorithms for identifying patients with OSA with the use of HA data. METHODS:
      Clinical data derived from an academic health sciences network within a universal
      health insurance plan were used as the reference standard. The authors linked
      patients to HA data and retrieved all claims in the 2 yr before surgery to
      determine the presence of any diagnostic codes, diagnostic procedures, or
      therapeutic interventions consistent with OSA. RESULTS: The authors identified
      4,965 patients (2003 to 2012) who underwent preoperative polysomnogram. Of these,
      4,353 patients were linked to HA data; 2,427 of these (56%) had OSA based on
      diagnosis by a sleep physician or the apnea hypopnea index. A claim for a
      polysomnogram and receipt of a positive airway pressure device had a sensitivity,
      specificity, and positive likelihood ratio (+LR) for OSA of 19, 98, and 10.9%,
      respectively. An International Classification of Diseases, Tenth Revision, code
      for sleep apnea in hospitalization abstracts was 9% sensitive and 98% specific
      (+LR, 4.5). A physician billing claim for OSA (International Classification of
      Diseases, Ninth Revision, 780.5) was 58% sensitive and 38% specific (+LR, 0.9). A
      polysomnogram and a positive airway pressure device or any code for OSA was 70%
      sensitive and 36% specific (+LR, 1.1). CONCLUSIONS: No code or combination of
      codes provided a +LR high enough to adequately identify patients with OSA.
      Existing studies using administrative codes to identify OSA should be interpreted
      with caution.

PMID- 26200179
TI  - N-terminal pro-B-type Natriuretic Peptides' Prognostic Utility Is Overestimated
      in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds.
AB  - BACKGROUND: N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic
      utility is commonly determined post hoc by identifying a single optimal
      discrimination threshold tailored to the individual study population. The authors
      aimed to determine how using these study-specific post hoc thresholds impacts
      meta-analysis results. METHODS: The authors conducted a systematic review of
      studies reporting the ability of preoperative NT-proBNP measurements to predict
      the composite outcome of all-cause mortality and nonfatal myocardial infarction
      at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP
      thresholds were determined using two different methodologies. First, a single
      combined NT-proBNP threshold was determined for the entire cohort of patients,
      and a meta-analysis conducted using this single threshold. Second, study-specific
      thresholds were determined for each individual study, with meta-analysis being
      conducted using these study-specific thresholds. RESULTS: The authors obtained
      individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP
      cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP
      measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific
      thresholds, the OR associated with an increased NT-proBNP measurement was 6.45
      (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort
      threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared
      with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds.
      CONCLUSIONS: Post hoc identification of study-specific prognostic biomarker
      thresholds artificially maximizes biomarker predictive power, resulting in an
      amplification or overestimation during meta-analysis of these results. This
      effect is accentuated in small studies.

PMID- 26200181
TI  - Association between Withholding Angiotensin Receptor Blockers in the Early
      Postoperative Period and 30-day Mortality: A Cohort Study of the Veterans Affairs
      Healthcare System.
AB  - BACKGROUND: Despite widespread use, there is limited information to guide
      perioperative management of angiotensin receptor blockers (ARBs). METHODS: In
      this retrospective cohort study, the authors evaluated the patterns of
      postoperative ARB use in veterans regularly prescribed ARBs admitted for
      noncardiac surgery at the Veterans Affairs Healthcare system between 1999 and
      2011. Multivariable and propensity score-matched Cox proportional hazards models
      were used to determine the independent effect of failure to resume ARB by
      postoperative day 2 on the primary outcome of all-cause 30-day mortality.
      RESULTS: Out of 1,167,482 surgical admissions, 30,173 inpatient surgical
      admissions met inclusion criteria. Approximately 10,205 patients (33.8%) in the
      cohort did not resume ARB by day 2. Those that resumed ARB had a 30-day mortality
      rate of 1.3% (260 of 19,968), whereas 3.2% (323 of 10,205) died in the group that
      withheld ARB. The unadjusted hazard ratio (HR) for 30-day mortality was 2.45 (95%
      CI, 2.08 to 2.89; P < 0.001) for those that withheld ARB compared with those that
      resumed, whereas the multivariable adjusted HR was 1.74 (95% CI, 1.47 to 2.06; P
      < 0.001). When restricted to a propensity score-matched subset of 19,490, the HR
      was similar (1.47; 95% CI, 1.22 to 1.78; P < 0.001). Withholding ARB in younger
      patients increased mortality risk (HR = 2.52; 95% CI, 1.69 to 3.76; P < 0.001 for
      age <60 yr) compared with older patients (HR = 1.42; 95% CI, 1.09 to 1.85; P =
      0.01 for age >75 yr). CONCLUSIONS: Postoperative delay in resuming ARB is common,
      particularly in patients who are frail after surgery. Withholding ARB is strongly
      associated with increased 30-day mortality, especially in younger patients,
      although residual confounding may be present.

PMID- 26200180
TI  - Hyperinsulinemic Normoglycemia Does Not Meaningfully Improve Myocardial
      Performance during Cardiac Surgery: A Randomized Trial.
AB  - BACKGROUND: Glucose-insulin-potassium (GIK) administration during cardiac surgery
      inconsistently improves myocardial function, perhaps because hyperglycemia
      negates the beneficial effects of GIK. The hyperinsulinemic normoglycemic clamp
      (HNC) technique may better enhance the myocardial benefits of GIK. The authors
      extended previous GIK investigations by (1) targeting normoglycemia while
      administering a GIK infusion (HNC); (2) using improved echocardiographic measures
      of myocardial deformation, specifically myocardial longitudinal strain and strain
      rate; and (3) assessing the activation of glucose metabolic pathways. METHODS: A
      total of 100 patients having aortic valve replacement for aortic stenosis were
      randomly assigned to HNC (high-dose insulin with concomitant glucose infusion
      titrated to normoglycemia) versus standard therapy (insulin treatment if glucose
      >150 mg/dl). The primary outcomes were left ventricular longitudinal strain and
      strain rate, assessed using speckle-tracking echocardiography. Right atrial
      tissue was analyzed for activation of glycolysis/pyruvate oxidation and
      alternative metabolic pathways. RESULTS: Time-weighted mean glucose
      concentrations were lower with HNC (127 +/- 19 mg/dl) than standard care (177 +/-
      41 mg/dl; P < 0.001). Echocardiographic data were adequate in 72 patients for
      strain analysis and 67 patients for strain rate analysis. HNC did not improve
      myocardial strain, with an HNC minus standard therapy difference of -1.2% (97.5%
      CI, -2.9 to 0.5%; P = 0.11). Strain rate was significantly better, but by a
      clinically unimportant amount: -0.16 s (-0.30 to -0.03 s; P = 0.007). There was
      no evidence of increased glycolytic, pyruvate oxidation, or hexosamine
      biosynthetic pathway activation in right atrial samples (HNC, n = 20; standard
      therapy, 22). CONCLUSION: Administration of glucose and insulin while targeting
      normoglycemia during aortic valve replacement did not meaningfully improve
      myocardial function.

PMID- 26200182
TI  - A Perioperative Course of Gabapentin Does Not Produce a Clinically Meaningful
      Improvement in Analgesia after Cesarean Delivery: A Randomized Controlled Trial.
AB  - BACKGROUND: Studies examining the efficacy of a single preoperative dose of
      gabapentin for analgesia after cesarean delivery (CD) have been inconclusive. The
      authors hypothesized that a perioperative course of gabapentin would improve
      analgesia after CD. METHODS: This single-center, randomized, double-blind,
      placebo-controlled, parallel-group, superiority trial was designed to determine
      the analgesic efficacy of a perioperative course of gabapentin when added to a
      multimodal analgesic regimen. Women scheduled for elective CD during spinal
      anesthesia were randomized to receive a perioperative oral course of either
      gabapentin (600 mg preoperatively followed by 200 mg every 8 h for 2 days) or
      placebo. Postoperative pain was measured at 24 and 48 h, at rest and on movement,
      on a visual analogue scale (VAS, 0 to 100 mm). The primary outcome was pain on
      movement at 24 h. Neonatal outcomes, opiate consumption, VAS satisfaction (0 to
      100 mm), adverse effects, and persistent pain were also assessed. RESULTS:
      Baseline characteristics were similar between groups. There was a statistically
      significant but small reduction in VAS pain score (mean [95% CI]) on "movement"
      (40 mm [36 to 45] vs. 47 mm [42 to 51]; difference, -7 mm [-13 to 0]; P = 0.047)
      at 24 h in the gabapentin (n = 100) compared with control group (n = 97). There
      was more sedation in the gabapentin group at 24 h (55 vs. 39%, P = 0.026) but
      greater patient VAS satisfaction (87 vs. 77 mm, P = 0.003). CONCLUSIONS: A
      perioperative course of gabapentin produces a clinically insignificant
      improvement in analgesia after CD and is associated with a higher incidence of
      sedation.

PMID- 26200183
TI  - Sphingosine 1-phosphate Receptor 2 Signaling Suppresses Macrophage Phagocytosis
      and Impairs Host Defense against Sepsis.
AB  - BACKGROUND: Sepsis is characterized by an inappropriate systemic inflammatory
      response and bacteremia that promote multiorgan failure and mortality.
      Sphingosine 1-phosphate receptor 2 (S1PR2) modulates endotoxin-induced
      inflammation in endothelium. However, as a highly expressed S1P receptor in
      macrophages, its role in regulating macrophage response to bacterial infection
      remains unclear. METHODS: Cecal ligation and puncture or intratracheal
      instillation of Escherichia coli was induced in wild-type or S1pr2-deficient
      mice. The antibacterial ability of cell-specific S1PR2 was tested in bone marrow
      reconstitution mice or mice with macrophage-specific deletion. Signaling
      molecules responsible for S1PR2-mediated phagocytosis were also measured in the
      bone marrow-derived macrophages. In addition, S1PR2 expression levels and its
      correlation with severity of sepsis were determined in critically ill patients (n
      = 25). RESULTS: Both genetic deletion and pharmaceutical inhibition of S1PR2
      significantly limited bacterial burden, reduced lung damage, and improved
      survival (genetic deletion, 0% in S1pr2 vs. 78.6% in S1pr2, P < 0.001;
      pharmaceutical inhibition, 9.1% in vehicle vs. 22.2% in S1PR2 antagonist, P <
      0.05). This protection was attributed to the enhanced phagocytic function of
      S1PR2-deficient macrophages (mean fluorescent intensity, 2035.2 +/- 202.1 vs.
      407.8 +/- 71.6, P < 0.001). Absence of S1PR2 in macrophage inhibits RhoA
      dependent cell contraction and promotes IQGAP1-Rac1-dependent lamellipodial
      protrusion, whose signaling pathways depend on extracellular stimulators. In
      septic patients, increased S1PR2 levels in peripheral blood mononuclear cells
      were positively correlated with the severity of sepsis (r = 0.845, P < 0.001).
      CONCLUSIONS: This study implies that S1PR2, as a critical receptor in macrophage,
      impairs phagocytosis and antimicrobial defense in the pathogenesis of sepsis.
      Interventions targeting S1PR2 signaling may serve as promising therapeutic
      approaches for sepsis.

PMID- 26200184
TI  - Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults: A
      Review of the Literature.
AB  - The estimated prevalence of subclinical hypothyroidism (SCH) in the general
      population is 3% to 8%. As the average age of the population in the United States
      and other countries continues to increase, the overall prevalence of SCH may also
      be expected to increase. Although age-related changes in thyroid function are
      well described, normal thyroid-stimulating hormone (TSH) reference limits,
      derived for age-specific populations, are not routinely used to identify thyroid
      dysfunction in elderly adults. Therefore, currently accepted values for the upper
      limit of normal of TSH may be inappropriate for diagnosing SCH in individuals
      aged 65 and older, resulting in potential overestimation of the prevalence of SCH
      in this population. This review discusses the current evidence of the effects of
      SCH on cardiovascular health and neuropsychiatric function in older adults.
      Although the results of some studies are conflicting, the overall evidence
      suggests that the consequences of SCH may be different for elderly adults than
      for younger populations. Treatment of SCH in older individuals requires special
      consideration with regard to thyroid hormone replacement therapy and expected
      clinical outcomes. Although careful identification of individuals with persistent
      SCH who could benefit from levothyroxine treatment is necessary, current evidence
      suggests that individuals with TSH levels greater than 10 mIU/L who test positive
      for antithyroid antibodies or are symptomatic may benefit from levothyroxine
      treatment to reduce the risk of progression to overt hypothyroidism, decrease the
      risk of adverse cardiovascular events, and improve their quality of life. After
      treatment is initiated, careful monitoring is essential. 

PMID- 26200186
TI  - A case of acetaminophen-induced acute interstitial nephritis and other
      complications.

PMID- 26200185
TI  - Diagnostic accuracy of serum cystatin C in chronic kidney disease: a meta
      analysis.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a major health problem worldwide with
      dramatically increasing incidence and prevalence. Serum cystatin C (sCysC) has
      been clarified by many studies as a relatively accurate marker to evaluate renal
      function. STUDY DESIGN: Meta-analysis of diagnostic test studies. SETTING AND
      POPULATION: Various clinical settings of CKD, including adult patients with
      diabetes, renal transplant patients, and so on. SELECTION CRITERIA: A
      computerized search of PubMed, Cochrane clinical trial database, and Current
      Contents (from inception until June 16, 2014) was performed to identify
      potentially relevant articles. INDEX TESTS: Increased sCysC concentration.
      REFERENCE TESTS: The measured glomerular filtration rate measured by nuclear
      medicine techniques such as 99Tc-diethylene triamine pentacaetic acid (99Tc-DTPA)
      or 51Cr-ethylenediamine tetra-acetic acid (51Cr-EDTA), or calculated by Cockcroft
      Gault (CG) or Modification of Diet in Renal Disease (MDRD) formula or 24 hours
      creatinine clearance rate. RESULTS: In total 19 studies were included in this
      study. Across all settings, the diagnostic odds ratio (DOR) of sCysC in
      predicting CKD was 40 (95% CI, 26 - 61) when sensitivity and specificity was 0.85
      (95% CI, 0.81 - 0.89) and 0.87 (95% CI, 0.84 - 0.90), respectively. The area
      under the curve for the receiver-operating characteristic (AUROC) of sCysC to
      predict CKD was 0.92 (95% CI, 0.90 - 0.94). For the diagnostic value of sCysC in
      diabetics with CKD, the DOR was 51 (95% CI, 22 - 122), with sensitivity and
      specificity of 0.89 and 0.87, respectively. Subgroup analysis showed that sCysC
      was of better diagnostic value in the West than in Asia, and the diagnostic value
      of sCysC assayed by particle-enhanced nephelometric immunoassay (PENIA) was
      higher than sCysC assayed by particle-enhanced turbidimetric immunoassay (PETIA).
      CONCLUSION: SCysC appears to be a good biomarker in the definition of CKD.
      However, its performance is different in subgroups restricted by clinical
      settings, race, and sCysC assay.

PMID- 26200187
TI  - The Physiological Mechanisms of Diabetes and Aging on Brain Health and Cognition:
      Implications for Nursing Practice and Research.
AB  - A substantial proportion of individuals over the age of 65 years will experience
      some degree of cognitive impairment, and older adults with diabetes are at
      increased risk for these impairments. Such impairments can negatively affect
      activities of daily living and lead to a decrease in quality of life as well as
      increase caregiver burden. Cumulatively, the effects of diabetes and aging slowly
      diminish cognitive function, resulting in various degrees of cognitive impairment
      including dementia. In fact, older adults with diabetes have a 65% higher chance
      of developing Alzheimer disease than those without diabetes. This article reviews
      the synergistic effects of aging and diabetes on cognitive function. A discussion
      of the physiologic basis for these effects is included, in particular, the role
      of insulin in the brain. The final section of the article focuses on intervention
      strategies that can be used by nurses and allied healthcare providers to mitigate
      the influence of diabetes and aging so that optimal cognitive performance is
      maintained. Areas for future research are also discussed. 

PMID- 26200188
TI  - Serious infection during etanercept, infliximab and adalimumab therapy for
      rheumatoid arthritis: A literature review.
AB  - The purpose of this review is to establish whether there is a significantly
      increased incidence of serious infections during treatment for rheumatoid
      arthritis (RA) with etanercept, infliximab or adalimumab, to determine the
      background risk of serious infection in RA patients without treatment with any
      biological therapy and to ascertain which organisms are involved in serious
      infections in RA patients while being treated with etanercept, infliximab or
      adalimumab. Randomised controlled trials (RCTs), meta-analyses of RCTs, Cochrane
      reviews, national registry articles and case reports were identified using
      PubMed/MEDLINE, The Cochrane Library and Google Scholar. The medical subject
      heading "rheumatoid arthritis" was combined with "serious infection" or
      "infection" or "adverse drug events" with each of the three reference biological
      therapies separately: etanercept, infliximab and adalimumab. These electronic
      searches were limited to human studies, adult studies, those published in the
      last 10 years (2004-14) and in the English language. Studies which involved the
      tumor necrosis factor-alpha inhibitors certolizumab pegol or golimumab were
      excluded. The background risk of serious infection appears to be approximately
      two-fold more than non-RA patients before any treatment with biological therapy.
      The national registries, which may represent the typical RA patient more
      accurately than clinical trials, suggest a small but significantly increased
      incidence of serious infection ranging 1.2-2.78 times that of control (treatment
      with methotrexate). Mycobacteria spp., Staphyloccus aureus, Listeria
      monocytogenes, Varicella zoster virus and Leishmania species (spp.) repeatedly
      appear in the case report literature and should be in the mind of the clinician
      faced with a serious infection in a RA patient with an unknown pathogen who is
      being treated with either etanercept, infliximab or adalimumab. 

PMID- 26200189
TI  - Evaluating resveratrol as a therapeutic bone agent: preclinical evidence from rat
      models of osteoporosis.
AB  - Resveratrol (RSV) is a naturally occurring plant polyphenol that has potential to
      attenuate osteoporosis with distinct pathologies. This review evaluates
      preclinical evidence regarding the efficacy and safety of RSV as a therapeutic
      bone agent using different rat models. Limitations of these animal models are
      discussed, and suggestions for strengthening the experimental design of future
      studies are provided. The ovariectomized rat model of postmenopausal osteoporosis
      reported that RSV supplementation attenuated estrogen deficiency-induced bone
      loss and trabecular structural deterioration. RSV safety was indicated by the
      absence of stimulation of estrogen-sensitive tissue. Providing RSV to rats aged
      >6 months attenuated age-related bone mass loss and structural deterioration but
      produced inconsistent effects on bones in rats aged <6 months. The hindlimb
      suspension rat model of disuse osteoporosis reported that RSV attenuated bone
      loss in old rats, but higher doses and longer duration supplementation before
      mechanical loading were required for younger rats. Limitations common to studies
      using rat models of osteoporosis include requirements to include animals that are
      skeletally mature, longer study durations, and to adjust for potential
      confounding effects due to altered body weight and endocrine function.
      Strengthening experimental design can contribute to translation of animal results
      to clinically relevant recommendations for humans. 

PMID- 26200190
TI  - Factor Structure and Internal Validity of the Functional Movement Screen in
      Adults.
AB  - The factor structure and internal consistency of the Functional Movement Screen
      (FMS) have not been examined in a general healthcare population. Replicating the
      factor structure of the FMS is important because it illustrates the
      interdependence between each of the subtests, enabling the strength and
      conditioning professional to better interpret and act on an individual's FMS
      score. Anthropometric data and FMS scores were collected from 1,113 clients of a
      multidisciplinary healthcare clinic in Vancouver, BC The mean (SD) ages were 53.4
      (11.1) for men (n = 656) and 49.3 (12.3) for women (n = 457). The mean FMS
      Summary Score was 13.7 (2.9) and was significantly negatively correlated with
      both age (r = -0.25; p < 0.001) and body mass index (r = -0.37; p < 0.001). The
      internal consistency of the FMS scale, which was assessed with both ordinal and
      Cronbach's alpha, was 0.73 and 0.64, respectively. Polychoric correlations
      between individual movements ranged from 0.03 to 0.59. Exploratory and
      confirmatory factor analyses (CFA) revealed that the FMS showed 2 main factors, a
      basic movement factor (shoulder mobility and active straight leg raise) and a
      complex movement factor (squat, hurdle step, inline lunge, and the trunk
      stability push-up). Rotary stability loaded onto both factors in the CFA, and its
      exclusion from the model had little effect. The findings of this study broadly
      replicated the intended factor structure of the FMS, as the individual movements
      aligned well with the intended factors.

PMID- 26200191
TI  - GPS and Injury Prevention in Professional Soccer.
AB  - This study investigated the relationship between GPS variables measured in
      training and gameplay and injury occurrences in professional soccer. Nineteen
      professional soccer players competing in the Australian Hyundai A-League were
      monitored for 1 entire season using 5 Hz Global Positioning System (GPS) units
      (SPI-Pro GPSports) in training sessions and preseason games. The measurements
      obtained were total distance, high-intensity running distance, very-high
      intensity running distance, new body load, and meters per minute. Noncontact soft
      tissue injuries were documented throughout the season. Players' seasons were
      averaged over 1- and 4-week blocks according to when injuries occurred. These
      blocks were compared with each other and with players' seasonal averages. Players
      performed significantly higher meters per minute in the weeks preceding an injury
      compared with their seasonal averages (+9.6 and +7.4% for 1- and 4-week blocks,
      respectively) (p < 0.01), indicating an increase in training and gameplay
      intensity leading up to injuries. Furthermore, injury blocks showed significantly
      lower average new body load compared with seasonal averages (-15.4 and -9.0% for
      1- and 4-week blocks, respectively) (p < 0.01 and p = 0.01). Periods of relative
      underpreparedness could potentially leave players unable to cope with intense
      bouts of high-intensity efforts during competitive matches. Although limited by
      Federation Internationale de Football Association regulations, the results of
      this study isolated 2 variables predicting soft tissue injuries for coaches and
      sports scientists to consider when planning and monitoring training.

PMID- 26200192
TI  - Evaluating Individual Training Adaptation With Smartphone-Derived Heart Rate
      Variability in a Collegiate Female Soccer Team.
AB  - Monitoring individual responses throughout training may provide insight to
      coaches regarding how athletes are coping to the current program. It is unclear
      if the evolution of heart rate variability (HRV) throughout training in team
      sport athletes can be useful in providing early indications of individual
      adaptation. This study evaluated relationships between changes in resting cardiac
      autonomic markers derived from a novel smartphone device within the first 3 weeks
      of a 5-week conditioning program and the eventual change in intermittent running
      performance at week 5 among 12 collegiate female soccer players. Change variables
      from weeks 1 to 3 of the weekly mean and weekly coefficient of variation for
      resting heart rate ([INCREMENT]RHRmean and [INCREMENT]RHRcv, respectively) and
      log-transformed root mean square of successive R-R intervals multiplied by 20
      ([INCREMENT]Ln rMSSDmean and [INCREMENT]Ln rMSSDcv, respectively) were compared
      with changes in Yo-Yo Intermittent Recovery Test Level 1 performance
      ([INCREMENT]Yo-Yo). A very large and significant correlation was found between
      [INCREMENT]Yo-Yo and [INCREMENT]Ln rMSSDcv (r = -0.74; p = <0.01) and a large
      nonsignificant correlation was found with [INCREMENT]Ln rMSSDmean (r = 0.50; p =
      0.096). This study suggests that a decrease in Ln rMSSDcv within the first 3
      weeks of training is a favorable response, indicative of positive adaptation.
      Collecting daily HRV data with a smartphone application using ultrashort HRV
      measures seems useful for athlete monitoring.

PMID- 26200193
TI  - Unilateral vs. Bilateral Squat Training for Strength, Sprints, and Agility in
      Academy Rugby Players.
AB  - The purpose of this study was to investigate the effects of a 5-week lower-limb
      unilateral or bilateral strength program on measures of strength, sprinting, and
      change of direction speed. Eighteen academy rugby players (18.1 +/- 0.5 years,
      97.4 +/- 11.3 kg, 183.7 +/- 11.3 cm) were randomly assigned to either a
      unilateral (UNI) or bilateral (BI) group. The UNI group squatted exclusively with
      the rear elevated split squat (RESS), whereas the BI group trained only with the
      bilateral back squat (BS). Both groups trained at a relative percentage of the
      respective 1 repetition maximum (1RM) twice weekly over a 5-week period. Subjects
      were assessed at baseline and postintervention for 1RM BS, 1RM RESS, 10-m sprint,
      40-m sprint, and pro-agility. There was a significant main effect of time for 1RM
      BS (F1,16 = 86.5, p < 0.001), ES (0.84 < Cohen d < 0.92), 1RM RESS (F1,16 =
      133.0, p < 0.001), ES (0.89 < Cohen d < 0.94), 40-m sprint (F1,16 = 14.4, p =
      0.002), ES (0.47 < Cohen d < 0.67) and pro-agility (F1,16 = 55.9, p < 0.001), ES
      (0.77 < Cohen d < 0.89), but not 10-m sprints (F1,16 = 2.69, p = 0.121), ES (0.14
      < Cohen d < 0.38). No significant interactions between group and time were
      observed for any of the dependent variables. This is the first study to suggest
      that BI and UNI training interventions may be equally efficacious in improving
      measures of lower-body strength, 40-m speed, and change of direction in academy
      level rugby players.

PMID- 26200194
TI  - Ginger (Zingiber officinale) as an Analgesic and Ergogenic Aid in Sport: A
      Systemic Review.
AB  - Ginger is a popular spice used to treat a variety of maladies, including pain.
      Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used by athletes to
      manage and prevent pain; unfortunately, NSAIDs contribute to substantial adverse
      effects, including gastrointestinal (GI) dysfunction, exercise-induced
      bronchoconstriction, hyponatremia, impairment of connective tissue remodeling,
      endurance competition withdrawal, and cardiovascular disease. Ginger, however,
      may act as a promoter of GI integrity and as a bronchodilator. Given these
      potentially positive effects of ginger, a systematic review of randomized trials
      was performed to assess the evidence for ginger as an analgesic and ergogenic aid
      for exercise training and sport. Among 7 studies examining ginger as an
      analgesic, the evidence indicates that roughly 2 g.d(-1) of ginger may modestly
      reduce muscle pain stemming from eccentric resistance exercise and prolonged
      running, particularly if taken for a minimum of 5 days. Among 9 studies examining
      ginger as an ergogenic aid, no discernable effects on body composition, metabolic
      rate, oxygen consumption, isometric force generation, or perceived exertion were
      observed. Limited data suggest that ginger may accelerate recovery of maximal
      strength after eccentric resistance exercise and reduce the inflammatory response
      to cardiorespiratory exercise. Major limitations to the research include the use
      of untrained individuals, insufficient reporting on adverse events, and no direct
      comparisons with NSAID ingestion. While ginger taken over 1-2 weeks may reduce
      pain from eccentric resistance exercise and prolonged running, more research is
      needed to evaluate its safety and efficacy as an analgesic for a wide range of
      athletic endeavors.

PMID- 26200195
TI  - Noninvasive Determination of Anaerobic Threshold Based on the Heart Rate
      Deflection Point in Water Cycling.
AB  - This study compared heart rate (HR), oxygen uptake (VO2), percentage of maximal
      HR (%HRmax), percentage of maximal VO2, and cadence (Cad) related to the
      anaerobic threshold (AT) during a water cycling maximal test between heart rate
      deflection point (HRDP) and ventilatory (VT) methods. In addition, the
      correlations between both methods were assessed for all variables. The test was
      performed by 27 men in a cycle ergometer in an aquatic environment. The protocol
      started at a Cad of 100 b . min(-1) for 3 minutes with subsequent increments of
      15 b . min(-1) every 2 minutes until exhaustion. A paired two-tailed Student's t
      test was used to compare the variables between the HRDP and VT methods. The
      Pearson product-moment correlation test was used to correlate the same variables
      determined by the 2 methods. There was no difference in HR (166 +/- 13 vs. 166 +/
      13 b . min(-1)), VO2 (38.56 +/- 6.26 vs. 39.18 +/- 6.13 ml . kg(-1) . min(-1)),
      %HRmax (89.24 +/- 3.84 vs. 89.52 +/- 4.29%), VO2max (70.44 +/- 7.99 vs. 71.64 +/-
      8.32%), and Cad (174 +/- 14 b . min(-1) vs. 171 +/- 8 b . min(-1)) related to AT
      between the HRDP and VT methods. Moreover, significant relationships were found
      between the methods to determine the AT for all variables analyzed (r = 0.57
      0.97). The estimation of the HRDP may be a noninvasive and easy method to
      determine the AT, which could be used to adapt individualized training
      intensities to practitioners during water cycling classes.

PMID- 26200196
TI  - Comparison of Methods That Assess Lower-body Stretch-Shortening Cycle
      Utilization.
AB  - The purpose of this study was to compare 4 methods that assess the lower-body
      stretch-shortening cycle (SSC) utilization of athletes. Eighty-six National
      Collegiate Athletic Association Division I athletes from 6 different sports
      performed 2 squat jumps and 2 countermovement jumps on a force platform. Pre
      stretch augmentation percentage (PSAP), eccentric utilization ratio (EUR), and
      reactive strength (RS) for jump height (JH) and peak power (PP) magnitudes, and
      reactive strength index-modified (RSImod) were calculated for each team. A series
      of one-way analyses of variance with a Holm-Bonferroni sequential adjustment were
      used to compare differences in PSAP, EUR, RS, and RSImod between teams.
      Statistical differences in RSImod (p < 0.001) existed between teams, whereas no
      statistical differences in PSAP-JH (p = 0.150), PSAP-PP (p = 0.200), EUR-JH (p =
      0.150), EUR-PP (p = 0.200), RS-JH (p = 0.031), or RS-PP (p = 0.381) were present.
      The relationships between PSAP, EUR, and RS measures were all statistically
      significant and ranged from strong to nearly perfect (r = 0.569-1.000), while
      most of the relationships between PSAP, EUR, and RS measures and RSImod were
      trivial to small (r = 0.192-0.282). Pre-stretch augmentation percentage and EUR,
      RS, and RSImod values indicate that women's tennis, men's soccer, and men's
      soccer teams may use the SSC most effectively, respectively. Pre-stretch
      augmentation percentage, EUR, RS, and RSImod values may show vastly different
      results when comparing an individual's and a team's ability to use the SSC.
      Practitioners should consider using RSImod to monitor the SSC utilization of
      athletes due to its timing component.

PMID- 26200197
TI  - Monitoring the Intended and Perceived Training Load of a Professional Futsal Team
      Over 45 Weeks: A Case Study.
AB  - The aims of this study were to compare the training load intended by a coach with
      the training load perceived by the players, over a 45-week professional futsal
      team season and to compare the variation of session rating of perceived exertion
      (sRPE) across different periods of the season. Eighteen Brazilian professional
      futsal players participated in the study. The players' rating of perceived
      exertion (RPE) and coach's rating of intended exertion (RIE) were collected daily
      throughout the study. To compare the sRPE variation, the season was divided into
      4 periods as follows: preseason (PRE-SEASON), first competitive period (COMP1),
      intercompetition period (INTER-COMP), and second competitive period (COMP2).
      Based on the cluster analyses, the training sessions were classified into 3
      different intensity zones (low, moderate, and high). In all the season periods
      and intensity zones, the players' RPEs were lower than the coach's RIE. In the
      low-intensity zone, the INTER-COMP demonstrated higher sRPE values than did the
      other periods. In the moderate-intensity zones, the INTER-COMP and COMP2 were
      similar. Finally, for the high-zone intensity, the PRE-SEASON demonstrated higher
      values than did the other periods. We concluded that the coach overestimated the
      training load reported by the players in almost all intensity training zones and
      season periods. The RPE scale does not seem to be a suitable tool when used by
      the coach for intended training load. Therefore, technical staff should
      constantly review the training goals in each season period through daily training
      load control, always taking into consideration the possibilities and limitations
      of the RPE method.

PMID- 26200198
TI  - Influence on Strength and Flexibility of a Swing Phase-Specific Hamstring
      Eccentric Program in Sprinters' General Preparation.
AB  - Hamstring injuries are common in sprinters and mainly occur during the terminal
      swing phase. Eccentric training has been shown to reduce hamstring injury rate by
      improving several risk factors. The aim of this study was to test the hypothesis
      that an additional swing phase-specific hamstring eccentric training in well
      trained sprinters performed at the commencement of the winter preparation is more
      efficient to improve strength, ratio, optimum angle, and flexibility than a
      similar program without hamstring eccentric exercises. Twenty sprinters were
      randomly allocated to an eccentric (n = 10) or a control group (n = 10). Both
      groups performed their usual track and field training throughout the study
      period. Sprinters in the eccentric group performed an additional 6-week hamstring
      eccentric program, which was specific to the swing phase of the running cycle
      (eccentric high-load open-chain kinetic movements covering the whole hamstring
      length-tension relationship preformed at slow to moderate velocity). Isokinetic
      and flexibility measurements were performed before and after the intervention.
      The eccentric group increased hamstring peak torques in concentric at 60 degrees 
      . s(-1) by 16% (p < 0.001) and at 240 degrees  . s(-1) by 10% (p < 0.01), in
      eccentric at 30 degrees  . s(-1) by 20% (p < 0.001) and at 120 degrees  . s(-1)
      by 22% (p < 0.001), conventional and functional ratios by 12% (p < 0.001), and
      flexibility by 4 degrees  (p < 0.01), whereas the control group increased
      hamstring peak torques only in eccentric at 30 degrees  . s(-1) by 6% (p <= 0.05)
      and at 120 degrees  . s(-1) by 6% (p < 0.01). It was concluded that an additional
      swing phase-specific hamstring eccentric training in sprinters seems to be
      crucial to address different risk factors for hamstring strain injuries, such as
      eccentric and concentric strength, hamstring-to-quadriceps ratio ratio, and
      flexibility.

PMID- 26200199
TI  - Adult stem cells: hopes and hypes of regenerative medicine.
AB  - Stem cells are self-renewing cells that can differentiate into specialized cell
      type(s). Pluripotent stem cells, i.e. embryonic stem cells (ESC) or induced
      pluripotent stem cells (iPSC) differentiate into cells of all three embryonic
      lineages. Multipotent stem cells, like hematopoietic stem cells (HSC), can
      develop into multiple specialized cells in a specific tissue. Unipotent cells
      differentiate only into one cell type, like e.g. satellite cells of skeletal
      muscle. There are many examples of successful clinical applications of stem
      cells. Over million patients worldwide have benefited from bone marrow
      transplantations performed for treatment of leukemias, anemias or
      immunodeficiencies. Skin stem cells are used to heal severe burns, while limbal
      stem cells can regenerate the damaged cornea. Pluripotent stem cells, especially
      the patient-specific iPSC, have a tremendous therapeutic potential, but their
      clinical application will require overcoming numerous drawbacks. Therefore, the
      use of adult stem cells, which are multipotent or unipotent, can be at present a
      more achievable strategy. Noteworthy, some studies ascribed particular adult stem
      cells as pluripotent. However, despite efforts, the postulated pluripotency of
      such events like "spore-like cells", "very small embryonic-like stem cells" or
      "multipotent adult progenitor cells" have not been confirmed in stringent
      independent studies. Also plasticity of the bone marrow-derived cells which were
      suggested to differentiate e.g. into cardiomyocytes, has not been positively
      verified, and their therapeutic effect, if observed, results rather from the
      paracrine activity. Here we discuss the examples of recent studies on adult stem
      cells in the light of current understanding of stem cell biology. 

PMID- 26200200
TI  - [Real-Life Evaluation of the Compact Program for Smoking Cessation].
AB  - Smoking cessation as a therapeutic intervention has largely not the significance
      that it should have according to its potential influence on diseases in the
      pulmonary practice. Barriers against smoking cessation apart from the addiction
      character of tobacco dependence are mainly the almost complete absence of
      reimbursement as well as concerns regarding low achievable long-term abstinence.
      The presented study shows that despite these barriers smoking cessation in
      pulmonology practice is successful if carried out by using a 2-step motivation of
      the participants. The long-term abstinence success of 46 % after 12 months (point
      prevalence) presented here was achieved with the use of behavioral therapy and
      medical support. Success factors are doctor's office setting and consequent
      information and encouragement for medical support (mostly varenicline). 

PMID- 26200202
TI  - Portable Detection of Melamine in Milk Using a Personal Glucose Meter Based on an
      in Vitro Selected Structure-Switching Aptamer.
AB  - Melamine detection in milk and other foods has attracted much attention since the
      discovery that melamine-adulterated food causes severe kidney damage. Although
      many methods have been developed to detect melamine, few methods can provide
      quantitative results using an affordable and portable device that is suitable for
      home use or field application. To achieve this goal, we herein report the first
      in vitro selection of a melamine responsive aptamer using a structure-switching
      method. A personal glucose meter (PGM) based melamine sensor was designed and
      subsequently tested using the newly isolated aptamer. Conversion of melamine
      concentration to glucose amount was achieved by including an invertase-conjugated
      DNA that is complementary to part of the aptamer. Melamine binding triggers the
      release of the invertase-DNA conjugate, which hydrolyzes sucrose into glucose.
      The glucose produced is then measured directly using an off-the-shelf PGM. The
      described sensor shows high selectivity for melamine against several closely
      related melamine analogues, such as cyanuric acid, ammeline, and ammelide, and
      has low detection limits of 0.33 MUM (or 41.1 ppb) in buffer and 0.53 MUM (or
      67.5 ppb) in 80% whole milk without any pretreatment. The detection limits meet
      the threshold of 2.5 ppm for non-infant-formula products and 1 ppm for melamine
      in infant milk products as defined by the U.S. Food and Drug Administration
      (FDA). In addition to the PGM sensor demonstrated here, the same aptamer can be
      converted into other types of sensors with different signal outputs, allowing
      portable detection of melamine under a variety of conditions. 

PMID- 26200203
TI  - Important Clarifications About Treating Indeterminate Vascular Injuries to the
      Neck.

PMID- 26200204
TI  - Switching-on luminescence in anilate-based molecular materials.
AB  - A simple change of one chloro substituent on the chloranilate ligand with a cyano
      group dramatically affects the electronic properties of the anilate moiety
      inducing unprecedented luminescence properties in the class of anilate-based
      ligands and their metal complexes. Here we report on the optimized synthesis and
      full characterization, including photoluminescence, of the chlorocyananilate
      ligand (ClCNAn(2-)) (dianion of the 3-chloro-6-cyano-2,5-dihydroxybenzoquinone,
      H2ClCNC6O4), a unique example of a heterosubstituted anilate ligand whose
      electronic properties, optical properties and coordination chemistry have never
      been investigated to date, even though it has been known since 1966. The
      synthesis and full characterization of its tris-chelated metal complexes with
      Cr(iii), Fe(iii), and Al(iii) metal ions are also described herein. These
      complexes, formulated as [A]3[M(III)(ClCNAn)3] (A = (n-Bu)4N(+) or Ph4P(+);
      M(III) = Cr (), Fe (), Al ()), are isostructural. While and are potential
      molecular building blocks for the preparation of molecule-based magnets or
      paramagnetic conducting organic-inorganic hybrid systems, , instead, where the
      coordinated Al(iii) metal ions retain the luminescence of the ligand, represents
      a unique building block to achieve heterobimetallic assemblies showing emissive
      properties under visible light irradiation. 

PMID- 26200205
TI  - Computational and Experimental Studies of Phthaloyl Peroxide-Mediated
      Hydroxylation of Arenes Yield a More Reactive Derivative, 4,5-Dichlorophthaloyl
      Peroxide.
AB  - The oxidation of arenes by the reagent phthaloyl peroxide provides a new method
      for the synthesis of phenols. A new, more reactive arene oxidizing reagent, 4,5
      dichlorophthaloyl peroxide, computationally predicted and experimentally
      determined to possess enhanced reactivity, has expanded the scope of the reaction
      while maintaining a high level of tolerance for diverse functional groups. The
      reaction proceeds through a novel "reverse-rebound" mechanism with diradical
      intermediates. Mechanistic insight was achieved through isolation and
      characterization of minor byproducts, determination of linear free energy
      correlations, and computational analysis of substituent effects of arenes, each
      of which provided additional support for the reaction proceeding through the
      diradical pathway. 

PMID- 26200206
TI  - [Au5Mes5]: improved gram-scale synthesis and its use as a convenient precursor
      for halide-free supported gold nanoparticles.
AB  - A simple one-step and gram-scale synthesis of [Au5Mes5] from AuCl3 was developed,
      and this molecular precursor was used to generate Au nanoparticles on SiO2 and
      Al2O3. While [Au5Mes5] does not react with surface silanols and is only
      physisorbed, its incipient wetness impregnation followed by H2 treatment leads to
      a narrow size distribution of 1.4 nm Au nanoparticles. In contrast, [Au5Mes5]
      reacts with partially dehydroxylated Al2O3 to directly yield 1 nm Au
      nanoparticles along with adsorbed species. A subsequent treatment under hydrogen
      leads to a narrow size distribution of smaller 0.8 nm Au particles. 

PMID- 26200208
TI  - Using Naturally Occurring Radionuclides To Determine Drinking Water Age in a
      Community Water System.
AB  - Drinking water quality in a community water system is closely linked to the age
      of water from initial treatment to time of delivery. However, water age is
      difficult to measure with conventional chemical tracers; particularly in stagnant
      water, where the relationship between disinfectant decay, microbial growth, and
      water age is poorly understood. Using radionuclides that were naturally present
      in source water, we found that measured activity ratios of (90)Y/(90)Sr and
      (234)Th/(238)U in discrete drinking water samples of known age accurately
      estimated water age up to 9 days old (sigmaest: +/- 3.8 h, P < 0.0001, r(2) =
      0.998, n = 11) and 25 days old (sigmaest: +/- 13.3 h, P < 0.0001, r(2) = 0.996, n
      = 12), respectively. Moreover, (90)Y-derived water ages in a community water
      system (6.8 * 10(4) m(3) d(-1) capacity) were generally consistent with water
      ages derived from an extended period simulation model. Radionuclides differ from
      conventional chemical tracers in that they are ubiquitous in distribution mains
      and connected premise plumbing. The ability to measure both water age and an
      analyte (e.g., chemical or microbe) in any water sample at any time allows for
      new insight into factors that control drinking water quality.

PMID- 26200207
TI  - Pulsed Electromagnetic Fields Enhance Bone Morphogenetic Protein-2 Dependent-Bone
      Regeneration.
AB  - The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the
      purpose of promoting bone regeneration is emerging; however, the high dose of
      rhBMP-2 required in humans is accompanied by several limitations, including bone
      resorption and swelling. To reduce the dose of rhBMP-2 required, the
      applicability of pulsed electromagnetic fields (PEMF) was evaluated using a rat
      calvarial defect model. After creating an 8-mm-diameter calvarial bone defect, a
      collagen sponge soaked in different concentrations (0, 2.5, 5, 10 MUg) of rhBMP-2
      was implanted at the defect area. One week after surgery, PEMF was applied for 8
      h/day over 5 days in an experimental group of animals (n = 28) using a width of
      12 MUs, a pulse frequency of 60 Hz, and a magnetic intensity of 10 G. Animals
      were sacrificed 4 weeks after surgery and assessed by microcomputed tomography
      and histological and immunohistochemical analyses. In the absence of application
      of PEMF, bone volume, bone mineral density, trabecular thickness, trabecular
      number, and trabecular separation, all showed statistically significant
      differences, depending on the concentration of rhBMP-2 utilized (p < 0.001). PEMF
      accelerated bone regeneration in the groups that received 0, 2.5, and 5 MUg rhBMP
      2 (p < 0.05). In contrast, administration of 10 MUg rhBMP-2 resulted in no
      additive effect on bone regeneration in combination with PEMF. Groups receiving
      no rhBMP-2 showed distinct bone regeneration in the central zone of the bone
      defect when treated with PEMF, whereas they failed to bridge the defect space
      without PEMF. Among the groups without PEMF, soft tissue infiltrations from the
      outer surface on the skin side were common. Among groups with PEMF, the groups
      receiving 5 and 10 MUg rhBMP-2 displayed denser bone with significantly reduced
      dead spaces. The application of PEMF did not result in an accelerated effect on
      bone regeneration in groups treated with 10 MUg rhBMP-2. Therefore, our data
      demonstrate that PEMF can promote bone regeneration in animals treated with a low
      concentration of rhBMP-2.

PMID- 26200209
TI  - Monitoring of the Enzymatic Degradation of Protein Corona and Evaluating the
      Accompanying Cytotoxicity of Nanoparticles.
AB  - Established nanobio interactions face the challenge that the formation of
      nanoparticle-protein corona complexes shields the inherent properties of the
      nanoparticles and alters the manner of the interactions between nanoparticles and
      biological systems. Therefore, many studies have focused on protein corona
      mediated nanoparticle binding, internalization, and intracellular transportation.
      However, there are a few studies to pay attention to if the corona encounters
      degradation after internalization and how the degradation of the protein corona
      affects cytotoxicity. To fill this gap, we prepared three types of off/on
      complexes based on gold nanoparticles (Au NPs) and dye-labeled serum proteins and
      studied the extracellular and intracellular proteolytic processes of protein
      coronas as well as their accompanying effects on cytotoxicity through multiple
      evaluation mechanisms, including cell viability, adenosine triphosphate (ATP)
      content, mitochondrial membrane potential (MMP), and reactive oxygen species
      (ROS). The proteolytic process was confirmed by recovery of the fluorescence of
      the dye-labeled protein molecules that was initially quenched by Au NPs. Our
      results indicate that the degradation rate of protein corona is dependent on the
      type of the protein based on systematical evaluation of the extracellular and
      intracellular degradation processes of the protein coronas formed by human serum
      albumin (HSA), gamma-globulin (HGG), and serum fibrinogen (HSF). Degradation is
      the fastest for HSA corona and the slowest for HSF corona. Notably, we also find
      that the Au NP-HSA corona complex induces lower cell viability, slower ATP
      production, lower MMP, and higher ROS levels. The cytotoxicity of the
      nanoparticle-protein corona complex may be associated with the protein corona
      degradation process. All of these results will enrich the database of
      cytotoxicity induced by nanomaterial-protein corona complexes. 

PMID- 26200210
TI  - Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via
      Reductive Amination with Lysine Residues.
AB  - We evaluated the efficacy of bioconjugation of oligodeoxynucleotides (ODNs)
      containing 1,4-dicarbonyl groups, a C4'-oxidized abasic site (OAS), and a newly
      designed 2'-methoxy analogue, via reductive amination with lysine residues.
      Dicarbonyls, aldehyde and ketone at C1- and C4-positions of deoxyribose in the
      ring-opened form of OAS allowed efficient reaction with amines. Kinetic studies
      indicated that reductive amination of OAS-containing ODNs with a proximal amine
      on the complementary strand proceeded 10 times faster than the corresponding
      reaction of an ODN containing an abasic site with C1-aldehyde. Efficient
      reductive amination between the DNA-binding domain of Escherichia coli DnaA
      protein and ODNs carrying OAS in the DnaA-binding sequence proceeded at the
      lysine residue in proximity to the phosphate group at the 5'-position of the OAS,
      in contrast to unsuccessful conjugation with abasic site ODNs, even though they
      have similar aldehydes. Theoretical calculation indicated that the C1-aldehyde of
      OAS was more accessible to the target lysine than that of the abasic site. These
      results demonstrate the potential utility of cross-linking strategies that use
      dicarbonyl-containing ODNs for the study of protein-nucleic acid interactions.
      Conjugation with a lysine-containing peptide that lacked specific affinity for
      ODN was also successful, further highlighting the advantages of 1,4-dicarbonyls. 

PMID- 26200211
TI  - Language Ability Groups in Bilingual Children: A Latent Profile Analysis.
AB  - PURPOSE: Classifying children into two language ability groups, with and without
      language impairment, may underestimate the number of groups with distinct
      language ability patterns, or, alternatively, there may be only a single group
      characterized by a continuum of language performance. The purpose of the current
      study was to identify the number and characteristics of latent (unobservable)
      language ability groups in an unclassified sample of predominantly Spanish
      speaking children. METHOD: An unclassified sample of 431 predominantly Spanish
      speaking 5- to 7-year-olds learning English participated in the study. The groups
      were identified on the basis of (a) language sample analyses (semantic,
      grammatical, and sentence-length measures); (b) language processing tasks
      (phonological working memory and processing speed measures); and (c) nonverbal
      cognitive abilities assessed using a standardized measure. All tasks were
      administered in Spanish. Latent profile analysis was used to examine the number
      and nature of distinct language ability groups in the unclassified sample.
      RESULTS: Results indicated that a three-group model best represented the data,
      characterized by low grammaticality in one group, low phonological working memory
      in another group, and average skills in a third group. CONCLUSION: Classifying
      children into two groups, those with and without language impairment, may lead to
      misidentification of language impairment.

PMID- 26200213
TI  - Effect of annealing in oxygen on alloy structures of Pd-Au bimetallic model
      catalysts.
AB  - It has been reported that Pd-Au bimetallic catalysts display improved catalytic
      performance after adequate calcination. In this study, a model catalyst study was
      conducted to investigate the effects of annealing in oxygen on the surface
      structures of Pd-Au alloys by comparing the physicochemical properties of
      Pd/Au(111) surfaces that were annealed in ultrahigh vacuum (UHV) versus in an
      oxygen ambient. Auger electron spectroscopy (AES) and Basin hopping simulations
      reveal that the presence of oxygen can inhibit the diffusion of surface Pd atoms
      into the subsurface of the Au(111) sample. Reflection-absorption infrared
      spectroscopy using CO as a probe molecule (CO-RAIRS) and King-Wells measurements
      of O2 uptake suggest that surfaces annealed in an oxygen ambient possess more
      contiguous Pd sites than surfaces annealed under UHV conditions. The oxygen
      annealed Pd/Au(111) surface exhibited a higher activity for CO oxidation in
      reactive molecular beam scattering (RMBS) experiments. This enhanced activity
      likely results from the higher oxygen uptake and relatively facile dissociation
      of oxygen admolecules due to stronger adsorbate-surface interactions as suggested
      by temperature-programmed desorption (TPD) measurements. These observations
      provide fundamental insights into the surface phenomena of Pd-Au alloys, which
      may prove beneficial in the design of future Pd-Au catalysts. 

PMID- 26200212
TI  - Keratinocyte growth factor receptor: a therapeutic target in solid cancer.
AB  - INTRODUCTION: The treatment effects of advanced solid cancer are unsatisfactory,
      and novel therapeutic approaches are much needed. Keratinocyte growth factor
      receptor (KGFR) is a receptor tyrosine kinase that is primarily localized on
      epithelial cells. KGFR may play important roles in epithelial cell proliferation
      and differentiation, epithelial wound repair, embryonic development, immunity,
      tumor formation and development. AREAS COVERED: This review summarizes the
      expression, function and mechanism of KGFR in solid cancer, and analyzes its
      value for the cancer therapy. Furthermore, this study discusses the limitations
      of KGFR-based therapy, and envisages future developments in the clinical
      applications of KGFR. EXPERT OPINION: KGFR may function as an ideal therapeutic
      target for solid cancer. Continued basic investigation of KGFR-mediated pathways
      will push insight into the novel strategies of target therapy. More in vivo
      studies and clinical trials should be performed to promote the translational
      bridging of the latest research into clinical application.

PMID- 26200214
TI  - Comparative Effectiveness of Chemotherapy Regimens in Prolonging Survival for Two
      Large Population-Based Cohorts of Elderly Adults with Breast and Colon Cancer in
      1992-2009.
AB  - OBJECTIVES: To compare the effectiveness of chemotherapy in prolonging survival
      according to age in breast and colon cancer. DESIGN: Retrospective cohort study
      with a matched cohort analysis based on the conditional probability of receiving
      chemotherapy. SETTING: The 16 Surveillance, Epidemiology, and End Results (SEER)
      areas from the SEER-Medicare linked database. PARTICIPANTS: Women diagnosed with
      Stage I to IIIa hormone receptor-negative breast cancer (n = 14,440) and 26,893
      men and women with Stage III colon cancer (n = 26,893) aged 65 and older in 1992
      to 2009. MEASUREMENTS: The main exposure was the receipt of chemotherapy, and the
      main outcome was mortality. RESULTS: In women with breast cancer aged 65 to 69,
      the risk of all-cause mortality was statistically significantly lower in those
      who received chemotherapy than in those who did not in the entire cohort (hazard
      ratio (HR) = 0.70, 95% confidence interval (CI) = 0.57-0.88) and in a propensity
      matched cohort (HR = 0.82, 95% CI = 0.70-0.96) after adjusting for measured
      confounders. These patterns were similar in participants aged 70 to 74 and 75 to
      79, but in women aged 80 to 84 and 85 to 89, risk of all-cause mortality was no
      longer significantly lower in those receiving chemotherapy in the entire and
      matched cohorts, except that, in a small number of women who received doxorubicin
      (Adriamycin) and cyclophosphamide (Cytoxan), risk of mortality was significantly
      lower for those aged 80 to 84. Chemotherapy appeared to be effective in all ages
      from 65 through 84 in participants with Stage III colon cancer. For example, in
      those aged 85 to 89, chemotherapy was significantly associated with lower risk of
      mortality in the entire cohort (HR = 0.79, 95% CI = 0.67-0.92) and the matched
      cohort (HR = 0.79, 95% CI = 0.66-0.95). CONCLUSION: The effectiveness of
      chemotherapy decreased with age in participants with breast cancer, in whom
      chemotherapy appears to be effective until age 79 except for the doxorubicin
      cyclophosphamide combination, which was effective in participants aged 80 to 84.
      In individuals with Stage III colon cancer, chemotherapy appears to be effective
      to age 89. These findings were consistent with those of randomized clinical
      trials.

PMID- 26200215
TI  - Enhancement of Radiative Plasmon Decay by Hot Electron Tunneling.
AB  - Here we demonstrate that photon emission induced by inelastic tunneling through a
      nanometer single gap between a sharp Au tip and an Au substrate can be
      significantly enhanced by the illumination of the junction with 634 nm laser
      light with an electric field component oriented parallel to the tip-axis, i.e.,
      perpendicular to the sample. Analyzing photoluminescence (PL) spectra recorded as
      a function of bias voltage allows us to distinguish between PL from (1) the decay
      of electron-hole pairs created by the laser excited sp/d interband transition
      with a characteristic band at 690 nm and (2) the red-shifted radiative decay of
      characteristic plasmon modes formed by the gap. Since the electroluminescence
      spectra (without laser) already show the plasmonic gap modes, we conclude that
      the enhanced intensity induced by laser illumination originates from the
      radiative decay of hot electrons closely above the Fermi level via inelastic
      tunneling and photon emission into the plasmon modes. Since these processes can
      be independently controlled by laser illumination and the amplitude of the bias
      voltage, it is of great interest for designing new switchable photon emission
      plasmonic devices. 

PMID- 26200216
TI  - Facilitated diffusion framework for transcription factor search with
      conformational changes.
AB  - Cellular responses often require the fast activation or repression of specific
      genes, which depends on transcription factors (TFs) that have to quickly find the
      promoters of these genes within a large genome. TFs search for their DNA promoter
      target by alternating between bulk diffusion and sliding along the DNA, a
      mechanism known as facilitated diffusion. We study a facilitated diffusion
      framework with switching between three search modes: a bulk mode and two sliding
      modes triggered by conformational changes between two protein conformations. In
      one conformation (search mode) the TF interacts unspecifically with the DNA
      backbone resulting in fast sliding. In the other conformation (recognition mode)
      it interacts specifically and strongly with DNA base pairs leading to slow
      displacement. From the bulk, a TF associates with the DNA at a random position
      that is correlated with the previous dissociation point, which implicitly is a
      function of the DNA structure. The target affinity depends on the conformation.
      We derive exact expressions for the mean first passage time (MFPT) to bind to the
      promoter and the conditional probability to bind before detaching when arriving
      at the promoter site. We systematically explore the parameter space and compare
      various search scenarios. We compare our results with experimental data for the
      dimeric Lac repressor search in E. coli bacteria. We find that a coiled DNA
      conformation is absolutely necessary for a fast MFPT. With frequent spontaneous
      conformational changes, a fast search time is achieved even when a TF becomes
      immobilized in the recognition state due to the specific bindings. We find a MFPT
      compatible with experimental data in presence of a specific TF-DNA interaction
      energy that has a Gaussian distribution with a large variance. 

PMID- 26200217
TI  - Nonemployed Simple Carboxylate Ions in Well-Investigated Areas of Heterometallic
      Carboxylate Cluster Chemistry: A New Family of {Cu(II)4Ln(III)8} Complexes
      Bearing tert-Butylacetate Bridging Ligands.
AB  - The first use of tert-butylacetate as bridging ligand in 3d/4f-metal cluster
      chemistry, in conjunction with the versatile chelate ligand pyridine-2,6
      dimethanol, has afforded a new family of [Cu4Ln8(OH)6(NO3)2(O2CCH2Bu(t))16(pdm)4]
      clusters with unprecedented structures and slow magnetization relaxation for the
      {Cu(II)4Dy(III)8} member. The molecular structure of representative complex 1
      consists of a {Cu(II)4Gd(III)8} cage-like cluster built from two {CuGd3} cubanes
      which are linked to each other and to two {CuGd} subunits on opposite sides
      through two eta(2):eta(2):eta(2):MU5 NO3(-) ions. The metal ions are additionally
      bridged by MU3-OH(-), MU3-OR(-), and MU-OR(-) groups to give an overall
      [Cu4Gd8(MU5-NO3)2(MU3-OH)6(MU3-OR)2(MU-OR)8](14+) core. Peripheral ligation about
      the core is provided by the N,O,O-chelating part of the pdm(2-) groups and, more
      impressively, by the oxygen atoms of 16 bridging Bu(t)CH2CO2(-) ligands; the
      latter are arranged into five classes, adopting a total of six different binding
      modes with the metal centers. The combined work demonstrates the ligating
      flexibility of tert-butylacetate ion and its usefulness in the synthesis of new
      3d/4f-metal cluster compounds. 

PMID- 26200218
TI  - Bioactive Polycyclic Tetramate Macrolactams from Lysobacter enzymogenes and Their
      Absolute Configurations by Theoretical ECD Calculations.
AB  - Two new polycyclic tetramate macrolactams, lysobacteramides A (1) and B (2),
      together with HSAF (heat-stable antifungal factor, 3), 3-dehydroxy HSAF (4), and
      alteramide A (5) were isolated from a culture of Lysobacter enzymogenes C3 in
      nutrient yeast glycerol medium. Their structures were determined by MS and
      extensive NMR analysis. The absolute configurations of 1-5 were assigned by
      theoretical calculations of their ECD spectra. Although HSAF and analogues were
      reported from several microorganisms, their absolute configurations had not been
      established. The isolation and the absolute configurations of these compounds
      revealed new insights into the biosynthetic mechanism for formation of the
      polycycles. Compounds 1-4 exhibited cytotoxic activity against human carcinoma
      A549, HepG2, and MCF-7 cells with IC50 values ranging from 0.26 to 10.3 MUM.
      Compounds 2 and 3 showed antifungal activity against Fusarium verticillioides
      with IC50 value of 47.9 and 6.90 MUg/mL, respectively. 

PMID- 26200219
TI  - Dehydrogenation of n-Alkanes by Solid-Phase Molecular Pincer-Iridium Catalysts.
      High Yields of alpha-Olefin Product.
AB  - We report the transfer-dehydrogenation of gas-phase alkanes catalyzed by solid
      phase, molecular, pincer-ligated iridium catalysts, using ethylene or propene as
      hydrogen acceptor. Iridium complexes of sterically unhindered pincer ligands such
      as (iPr4)PCP, in the solid phase, are found to give extremely high rates and
      turnover numbers for n-alkane dehydrogenation, and yields of terminal
      dehydrogenation product (alpha-olefin) that are much higher than those previously
      reported for solution-phase experiments. These results are explained by
      mechanistic studies and DFT calculations which jointly lead to the conclusion
      that olefin isomerization, which limits yields of alpha-olefin from pincer-Ir
      catalyzed alkane dehydrogenation, proceeds via two mechanistically distinct
      pathways in the case of ((iPr4)PCP)Ir. The more conventional pathway involves 2,1
      insertion of the alpha-olefin into an Ir-H bond of ((iPr4)PCP)IrH2, followed by
      3,2-beta-H elimination. The use of ethylene as hydrogen acceptor, or high
      pressures of propene, precludes this pathway by rapid hydrogenation of these
      small olefins by the dihydride. The second isomerization pathway proceeds via
      alpha-olefin C-H addition to (pincer)Ir to give an allyl intermediate as was
      previously reported for ((tBu4)PCP)Ir. The improved understanding of the factors
      controlling rates and selectivity has led to solution-phase systems that afford
      improved yields of alpha-olefin, and provides a framework required for the future
      development of more active and selective catalytic systems. 

PMID- 26200220
TI  - Increasing Trend of Fatal Falls in Older Adults in the United States, 1992 to
      2005: Coding Practice or Reporting Quality?
AB  - OBJECTIVES: To investigate whether changes in death certificate coding and
      reporting practices explain part or all of the recent increase in the rate of
      fatal falls in adults aged 65 and older in the United States. DESIGN: Trends in
      coding and reporting practices of fatal falls were evaluated under mortality
      coding schemes for International Classification of Diseases (ICD), Ninth Revision
      (1992-1998) and Tenth Revision (1999-2005). SETTING: United States, 1992 to 2005.
      PARTICIPANTS: Individuals aged 65 and older with falls listed as the underlying
      cause of death (UCD) on their death certificates. MEASUREMENTS: The primary
      outcome was annual fatal falls rates per 100,000 U.S. residents aged 65 and
      older. Coding practice was assessed through analysis of trends in rates of
      specific UCD fall ICD e-codes over time. Reporting quality was assessed by
      examining changes in the location on the death certificate where fall e-codes
      were reported, in particular, the percentage of fall e-codes recorded in the
      proper location on the death certificate. RESULTS: Fatal falls rates increased
      over both time periods: 1992 to 1998 and 1999 to 2005. A single falls e-code was
      responsible for the increasing trend of fatal falls overall from 1992 to 1998
      (E888, other and unspecified fall) and from 1999 to 2005 (W18, other falls on the
      same level), whereas trends for other falls e-codes remained stable. Reporting
      quality improved steadily throughout the study period. CONCLUSION: Better
      reporting quality, not coding practices, contributed to the increasing rate of
      fatal falls in older adults in the United States from 1992 to 2005.

PMID- 26200221
TI  - An Optically Transparent Iron Nickel Oxide Catalyst for Solar Water Splitting.
AB  - Sunlight-driven water splitting to produce hydrogen fuel is an attractive method
      for renewable energy conversion. Tandem photoelectrochemical water splitting
      devices utilize two photoabsorbers to harvest the sunlight and drive the water
      splitting reaction. The absorption of sunlight by electrocatalysts is a severe
      problem for tandem water splitting devices where light needs to be transmitted
      through the larger bandgap component to illuminate the smaller bandgap component.
      Herein, we describe a novel method for the deposition of an optically transparent
      amorphous iron nickel oxide oxygen evolution electrocatalyst. The catalyst was
      deposited on both thin film and high-aspect ratio nanostructured hematite
      photoanodes. The low catalyst loading combined with its high activity at low
      overpotential results in significant improvement on the onset potential for
      photoelectrochemical water oxidation. This transparent catalyst further enables
      the preparation of a stable hematite/perovskite solar cell tandem device, which
      performs unassisted water splitting. 

PMID- 26200222
TI  - Preclinical testing of radiopharmaceuticals for novel applications in HIV,
      bacterial and fungal infectious diseases.
AB  - Antibiotics, antifungal and antiviral medications have traditionally been used in
      the management of infections. Due to widespread emergence of resistance to
      antimicrobial medications, and their side effects, there is a growing need for
      alternative approaches for management of such conditions. Antibiotic resistant
      bacterial pathogens are on the rise. A cure has not been achieved for viral
      infections like AIDS, while fungal and parasitic infections are constant threats
      to the health of general public. The incidence of opportunistic infections in
      immunocompromised individuals like HIV patients, patients receiving high dose
      steroids, chemotherapy patients, and organ transplant recipients is on the rise.
      Radioimmunotherapy (RIT) has the potential to be a suitable and viable
      therapeutic modality in the arena of infection management. Provided the target
      associated antigen is expressed by the target cells and minimally or not
      expressed by other tissues, selective targeting of radiation to target sites can
      be theoretically accomplished with relative sparing normal tissues from radiation
      exposure. In our laboratory we successfully demonstrated the effectiveness of RIT
      for treating infectious diseases. We targeted murine cryptococcosis with a mAb to
      the Cryptococcus neoformans capsular glucuronoxylomannan labeled with Bismuth-213
      ((213)Bi) or Rhenium-188 ((188)Re). We subsequently extended the applicability of
      RIT for treating bacterial and viral infections. One of the advantages of using
      RIT to treat infections as opposed to cancer is that, in contrast to tumor cells,
      cells expressing microbial antigens are antigenically very different from host
      tissues and thus provide the potential for exquisite specificity and low cross
      reactivity. Ever increasing incidence of infectious pathologies, exhaustion of
      antimicrobial possibilities and rising drug resistance calls for use of
      alternative and novel therapeutic options and we believe RIT is the need of the
      hour to combat these infections.

PMID- 26200223
TI  - Preclinical imaging and treatment of cancer: the use of animal models beyond
      rodents.
AB  - The development of novel radiopharmaceutical agents for imaging and therapy of
      neoplastic diseases relies on accurate and reproducible animal models. Rodent
      models are often used to demonstrate the proof-of-principle tracer and
      therapeutic agent development, but their small size can make tissue sampling
      challenging. The dosimetry of decay emissions in the much smaller rodent tumors
      do not model dosimetry in human tumors well. In addition, rodent models of cancer
      represent a simplified version of a very complex process. Spontaneous tumors are
      heterogenous and the response to intervention can be unpredictable; tumor cells
      can adopt alternate signaling pathways and modify their interaction with the
      microenvironment. These inconsistencies, while present in humans, are difficult
      to fully reproduce in a genetically-engineered rodent model. Companion animals,
      primarily dogs and cats, offer translational models that more accurately reflect
      the intricate nature of spontaneous neoplasia in humans. Their larger size
      facilitates tissue and blood sampling when needed, and allows radiopharmaceutical
      tracers to be studied on human-scale imaging systems to better mimic the clinical
      application of the agent. This article will review the growing body of literature
      surrounding the use of radiopharmaceutical agents for both imaging and therapy in
      companion dogs and cats. Previous investigations have been performed both for the
      advancement of routine, high-level veterinary care, and in the context of
      translational research from which the results of imaging and treatment can be
      readily applied to people. Studies utilizing the spontaneously occurring cancer
      model in companion animals involving positron emission tomography, radiotracers,
      dosimetry, theranostics, targeted radiopharmaceuticals, brachytherapy, and boron
      neutron capture therapy are discussed. 

PMID- 26200225
TI  - Assessment and Diagnosis of Posterior Tibial Tendon Dysfunction: Do We Share the
      Same Opinions and Beliefs?
AB  - BACKGROUND: Posterior tibial tendon dysfunction is a disabling pathologic
      flatfoot disorder. Evidence supports the notion that this condition is poorly
      diagnosed by health-care professionals. In addition, opinion is divided as to the
      most appropriate assessment and diagnostic techniques used to reflect the
      progression or stage of the condition. Hence, this study intended to explore the
      views and opinions of health-care professionals who may be involved in its
      assessment and diagnosis. METHODS: A two-phase sequential mixed methods design
      was used that combined a questionnaire survey and a focus group interview.
      RESULTS: The questionnaire data were analyzed using the Kendall levels of
      concordance and the Cohen kappa statistic, and the focus group data were analyzed
      using thematic analysis, which led to three main themes: resource implications,
      scope of practice, and awareness of the condition. CONCLUSIONS: This study
      highlights what may have been suspected previously but that has never been
      investigated in a structured manner. One approach to the assessment and diagnosis
      of posterior tibial tendon dysfunction is not necessarily the best, and depending
      on the clinical teams, different guidance may be required to ensure that patients
      are receiving the most appropriate and best care.

PMID- 26200226
TI  - Sex dimorphism in periodontitis in animal models.
AB  - BACKGROUND AND OBJECTIVE: Although surveys in the USA have shown that male
      subjects are more prone to develop periodontitis, sex as a risk factor in
      periodontitis, and its mechanism, remain controversial. Animal models are ideal
      for investigating immunological mechanisms of sex dimorphism in periodontitis
      because in these models it is possible to exclude the interference of gender
      related risk factors, such as smoking and oral hygiene habits. Based on surveys
      in humans and reports on sex dimorphism in other diseases, our hypothesis is that
      sex is a risk factor in periodontitis. MATERIAL AND METHODS: Different murine
      models (oral gavage model and ligature model) for periodontitis have been
      utilized to determine susceptibility to periodontitis in female and male mice.
      Periodontal bone levels were measured as the distance from the cemento-enamel
      junction to the alveolar bone crest (CEJ-ABC) in young female or male mice (8-10
      wk of age). Differential expression of inflammatory mediators in the gingivae of
      female and male mice was determined by quantitative real-time PCR. RESULTS: In
      comparison with male mice, female mice displayed significantly (p < 0.05)
      increased periodontal bone loss, accompanied by elevated expression of
      proinflammatory cytokines (interleukin-1beta, interleukin-6 and interleukin-17A)
      and higher numbers of oral bacteria. CONCLUSION: In contrast to the results in
      humans, in which periodontitis susceptibility is also influenced by confounding
      gender-related behaviors, in the murine oral gavage model and ligature model,
      female mice appear to be more susceptible to periodontal bone loss than male
      mice. In the ligature model, we observed significantly (p < 0.05) higher CEJ-ABC
      distance, gingival proinflammatory cytokine production and number of oral
      bacteria in female mice. Furthermore, our results imply that female mice develop
      periodontitis with a higher progression rate. Our study has therefore established
      that animal models can be used to dissect the mechanisms underlying genuine
      gender-based differences in periodontal disease susceptibility and/or
      progression.

PMID- 26200224
TI  - Ultrasound in Radiology: From Anatomic, Functional, Molecular Imaging to Drug
      Delivery and Image-Guided Therapy.
AB  - During the past decade, ultrasound has expanded medical imaging well beyond the
      "traditional" radiology setting: a combination of portability, low cost, and ease
      of use makes ultrasound imaging an indispensable tool for radiologists as well as
      for other medical professionals who need to obtain imaging diagnosis or guide a
      therapeutic intervention quickly and efficiently. Ultrasound combines excellent
      ability for deep penetration into soft tissues with very good spatial resolution,
      with only a few exceptions (ie, those involving overlying bone or gas). Real-time
      imaging (up to hundreds and thousands of frames per second) enables guidance of
      therapeutic procedures and biopsies; characterization of the mechanical
      properties of the tissues greatly aids with the accuracy of the procedures. The
      ability of ultrasound to deposit energy locally brings about the potential for
      localized intervention encompassing the following: tissue ablation, enhancing
      penetration through the natural barriers to drug delivery in the body and
      triggering drug release from carrier microparticles and nanoparticles. The use of
      microbubble contrast agents brings the ability to monitor and quantify tissue
      perfusion, and microbubble targeting with ligand-decorated microbubbles brings
      the ability to obtain molecular biomarker information, that is, ultrasound
      molecular imaging. Overall, ultrasound has become the most widely used imaging
      modality in modern medicine; it will continue to grow and expand. 

PMID- 26200227
TI  - Base-Promoted N-Pyridylation of Heteroarenes Using N-Propargyl Enaminones as
      Equivalents of Pyridine Scaffolds.
AB  - N-Pyridylation of various N-heteroarenes, including N-heteroarene-containing
      peptides, was achieved using N-propargyl enaminones (isolated or generated in
      situ from propargyl amine and propynones) as masked polysubstituted pyridine
      cores. This metal-free procedure proceeds under mild reaction conditions and
      generates 1 equiv of H2O as the sole byproduct. 

PMID- 26200228
TI  - Antibacterial and anti-inflammatory activities of an extract, fractions, and
      compounds isolated from Gochnatia pulchra aerial parts.
AB  - This paper reports on the in vitro antibacterial and in vivo anti-inflammatory
      properties of a hydroethanolic extract of the aerial parts of Gochnatia pulchra
      (HEGP). It also describes the antibacterial activity of HEGP fractions and of the
      isolated compounds genkwanin, scutellarin, apigenin, and 3,5-O-dicaffeoylquinic
      acid, as evaluated by a broth microdilution method. While HEGP and its fractions
      did not provide promising results, the isolated compounds exhibited pronounced
      antibacterial activity. The most sensitive microorganism was Streptococcus
      pyogenes, with minimum inhibitory concentration (MIC) values of 100, 50 and 25
      ug/mL for genkwanin and the flavonoids apigenin and scutellarin, respectively.
      Genkwanin produced an MIC value of 25 ug/mL against Enterococcus faecalis. A paw
      edema model in rats and a pleurisy inflammation model in mice aided investigation
      of the anti-inflammatory effects of HEGP. This study also evaluated the ability
      of HEGP to modulate carrageenan-induced interleukin-1 beta (IL-1beta), tumor
      necrosis factor alpha (TNF-alpha), and monocyte chemoattractant protein-1 (MCP-1)
      production. Orally administered HEGP (250 and 500 mg/kg) inhibited carrageenan
      induced paw edema. Regarding carrageenan-induced pleurisy, HEGP at 50, 100, and
      250 mg/kg diminished leukocyte migration by 71.43%, 69.24%, and 73.34% (P<0.05),
      respectively. HEGP suppressed IL-1beta and MCP-1 production by 55% and 50% at 50
      mg/kg (P<0.05) and 60% and 25% at 100 mg/kg (P<0.05), respectively. HEGP abated
      TNF-alpha production by macrophages by 6.6%, 33.3%, and 53.3% at 100, 250, and
      500 mg/kg (P<0.05), respectively. HEGP probably exerts anti-inflammatory effects
      by inhibiting production of the pro-inflammatory cytokines TNF-alpha, IL-1beta,
      and MCP-1. 

PMID- 26200229
TI  - A glycoprotein E gene-deleted bovine herpesvirus 1 as a candidate vaccine strain.
AB  - A bovine herpesvirus 1 (BoHV-1) defective in glycoprotein E (gE) was constructed
      from a Brazilian genital BoHV-1 isolate, by replacing the full gE coding region
      with the green fluorescent protein (GFP) gene for selection. Upon co-transfection
      of MDBK cells with genomic viral DNA plus the GFP-bearing gE-deletion plasmid,
      three fluorescent recombinant clones were obtained out of approximately 5000
      viral plaques. Deletion of the gE gene and the presence of the GFP marker in the
      genome of recombinant viruses were confirmed by PCR. Despite forming smaller
      plaques, the BoHV-1?gE recombinants replicated in MDBK cells with similar
      kinetics and to similar titers to that of the parental virus (SV56/90),
      demonstrating that the gE deletion had no deleterious effects on replication
      efficacy in vitro. Thirteen calves inoculated intramuscularly with BoHV-1?gE
      developed virus neutralizing antibodies at day 42 post-infection (titers from 2
      to 16), demonstrating the ability of the recombinant to replicate and to induce a
      serological response in vivo. Furthermore, the serological response induced by
      recombinant BoHV-1?gE could be differentiated from that induced by wild-type BoHV
      1 by the use of an anti-gE antibody ELISA kit. Taken together, these results
      indicated the potential application of recombinant BoHV-1 ?gE in vaccine
      formulations to prevent the losses caused by BoHV-1 infections while allowing for
      differentiation of vaccinated from naturally infected animals. 

PMID- 26200230
TI  - Decreased brain-derived neurotrophic factor plasma levels in psoriasis patients.
AB  - Brain-derived neurotrophic factor (BDNF) is associated with neuroplasticity and
      synaptic strength, and is decreased in conditions associated with chronic stress.
      Nevertheless, BDNF has not yet been investigated in psoriasis, a chronic
      inflammatory systemic disease that is exacerbated by stress. Therefore, our aim
      was to determine BDNF plasma levels in psoriasis patients and healthy controls.
      Adult patients (n=94) presenting with psoriasis for at least 1 year were
      enrolled, and age- and gender-matched with healthy controls (n=307) from the
      Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Participants had
      neither a previous history of coronary artery disease nor current episode of
      major depression. BDNF plasma levels were determined using the Promega ELISA kit.
      A general linear model was used to compare BDNF levels in psoriasis patients and
      controls, with age, gender, systolic blood pressure, serum fasting glucose, blood
      lipid levels, triglycerides, smoking status, and body mass index examined. After
      adjusting for clinical and demographic variables, significantly decreased BNDF
      plasma levels were observed in psoriasis patients (P=0.01) (estimated marginal
      means of 3922 pg/mL; 95%CI=2660-5135) compared with controls (5788 pg/mL;
      95%CI=5185-6442). Similar BDNF levels were found in both mild and severe cases of
      psoriasis. Our finding, that BDNF is decreased in psoriasis, supports the concept
      of a brain-skin connection in psoriasis. Further studies should determine if BDNF
      is increased after specific psoriasis treatments, and associated with different
      disease stages. 

PMID- 26200231
TI  - Caryocar brasiliense camb protects against genomic and oxidative damage in
      urethane-induced lung carcinogenesis.
AB  - The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi
      fruit, have not been evaluated to determine their protective effects against
      oxidative damage in lung carcinogenesis. In the present study, we evaluated the
      role of pequi fruit against urethane-induced DNA damage and oxidative stress in
      forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to
      assess DNA damage in lung tissues and changes in lipid peroxidation and redox
      cycle antioxidants were monitored for oxidative stress. Prior supplementation
      with pequi oil or its extract (15 uL, 60 days) significantly reduced urethane
      induced oxidative stress. A protective effect against DNA damage was associated
      with the modulation of lipid peroxidation and low protein and gene expression of
      nitric oxide synthase. These findings suggest that the intake of pequi fruit
      might protect against in vivo genotoxicity and oxidative stress. 

PMID- 26200232
TI  - Recovery of Walking Ability and Return to Community Living within 60 Days of Hip
      Fracture Does Not Differ Between Male and Female Survivors.
AB  - OBJECTIVES: To compare risk-adjusted differences between men and women 30 and 60
      days after hip fracture surgery in not walking, ability to return home in a
      community-dwelling subset, not walking in a nursing home resident subset, and
      mortality within 60 days. DESIGN: Cohort study. SETTING: Data were from a
      randomized clinical trial that compared two blood transfusion protocols after hip
      fracture. PARTICIPANTS: Individuals with hip fracture (N = 2,016; 489 (24%)
      male). MEASUREMENTS: Walking, dwelling, and mortality were determined in
      telephone follow-up 30 and 60 days after randomization, which occurred within 3
      days of surgery. Sex differences for each outcome were compared using univariate
      and multivariate regression adjusting for potential confounders. RESULTS: Men
      were younger (P < .001) and more likely to have comorbidity (P = .003) than women
      at the time of hip fracture and to die within 60 days, even after risk adjustment
      (odds ratio (OR) = 1.76, 95% confidence interval (CI) = 1.15-2.69). After risk
      adjustment, male survivors were as likely as female survivors not to walk (OR =
      1.03, 95% CI = 0.78-1.34) and no less likely to return home (OR = 0.90, 95% CI =
      0.69-1.17) 60 days after hip fracture. No differences were noted between male and
      female nursing home residents in not walking within 60 days (OR = 0.95, 95% CI =
      0.32-2.86). CONCLUSION: Although men experience higher mortality, male survivors
      can expect recovery of walking ability similar to that of female survivors and
      are as likely to return to community living.

PMID- 26200233
TI  - Serological Detection of Antibodies to Peste des Petits Ruminants Virus in Large
      Ruminants.
AB  - Peste des petits ruminants (PPR) is an economically important disease of small
      ruminants with a rapidly expanding geographical distribution. Peste des petits
      ruminants virus may manifest in a variety of ways with disease ranging from acute
      to subclinical. We investigated the exposure of large ruminants to PPRV in areas
      where the virus is endemic in the small ruminant population by assessing the
      serological status of groups of animals. This study focused on the Punjab
      province of Pakistan as an area where the virus is endemic and where mixed
      farming practices occur enabling close interactions between small and large
      ruminant populations. An overall PPR seropositivity was detected in 10.0% of
      cattle and 14.16% of buffaloes. Following an assessment of serological profiles
      in large ruminants within different age groups, a maximum seroprevalence was
      observed in cattle (17.5%) and buffaloes (22.5%) over 2 years of age indicating
      the potential utility of sampling large ruminant populations for PPR
      serosurveillance. The large ruminants sampled between one and two years of age
      had similar levels of seropositivity within populations with 11.2% and 16.2% of
      animals being seropositive, respectively. Current PPR vaccination strategies do
      not enable the differentiation between infected and vaccinated small ruminants,
      and as such, the serological surveillance of sheep and goats is of little value.
      When considering eradication programmes for PPRV, this factor is of great
      significance. However, where large and small ruminants are farmed together,
      serological surveillance of large ruminants may provide a snapshot of virus
      infection within populations where mild disease is present or where small
      ruminants are regularly vaccinated.

PMID- 26200234
TI  - Exploring possible mechanisms of action for the nanotoxicity and protein binding
      of decorated nanotubes: interpretation of physicochemical properties from optimal
      QSAR models.
AB  - Carbon nanotubes have become widely used in a variety of applications including
      biosensors and drug carriers. Therefore, the issue of carbon nanotube toxicity is
      increasingly an area of focus and concern. While previous studies have focused on
      the gross mechanisms of action relating to nanomaterials interacting with
      biological entities, this study proposes detailed mechanisms of action, relating
      to nanotoxicity, for a series of decorated (functionalized) carbon nanotube
      complexes based on previously reported QSAR models. Possible mechanisms of
      nanotoxicity for six endpoints (bovine serum albumin, carbonic anhydrase,
      chymotrypsin, hemoglobin along with cell viability and nitrogen oxide production)
      have been extracted from the corresponding optimized QSAR models. The molecular
      features relevant to each of the endpoint respective mechanism of action for the
      decorated nanotubes are also discussed. Based on the molecular information
      contained within the optimal QSAR models for each nanotoxicity endpoint, either
      the decorator attached to the nanotube is directly responsible for the expression
      of a particular activity, irrespective of the decorator's 3D-geometry and
      independent of the nanotube, or those decorators having structures that place the
      functional groups of the decorators as far as possible from the nanotube surface
      most strongly influence the biological activity. These molecular descriptors are
      further used to hypothesize specific interactions involved in the expression of
      each of the six biological endpoints. 

PMID- 26200235
TI  - Evidence-based practice in physical therapy in Austria: current state and factors
      associated with EBP engagement.
AB  - RATIONALE, AIMS AND OBJECTIVES: Research examining the use of evidence-based
      practice (EBP) in physical therapy in many countries has revealed positive
      attitudes, varying degrees of EBP use and barriers at practitioner, patient and
      organizational levels. In contrast to these countries, Austria does not have an
      academic or research tradition in physical therapy. Engagement in EBP in
      countries such as Austria is unknown. The objectives of the study were to
      describe the current state of EBP engagement and identify factors associated with
      EBP engagement among Austrian physical therapists (PTs). METHODS: A cross
      sectional online survey was conducted. Existing questionnaires and the theory of
      planned behaviour guided questionnaire development. Face and content validity and
      ease of use of the questionnaire were evaluated in pilot tests. Item-level
      response frequencies and percentages were determined. Simple and multiple
      regressions were used to identify factors associated with EBP engagement.
      RESULTS: The final sample size was 588 (response rate: 17.5%). Ten percent of
      participants fully agreed that they regularly use guidelines and standardized
      assessment tools in clinical practice. While 49.9% reported not using electronic
      databases for literature searching, 41.9% reported reading research articles 2-5
      times per month. Most frequently cited barriers to EBP engagement were lack of
      scientific skills, lack of time and insufficient organizational support. Research
      awareness, attitude, behavioural control, involvement in research and degree
      level were final correlates of EBP engagement. CONCLUSION: Austrian PTs show a
      low level of engagement in EBP. Initiatives to advance EBP in Austria and other
      countries with no academic or research tradition should primarily target
      practitioner-level factors.

PMID- 26200236
TI  - Ethnic Differences in Effects of Maternal Pre-Pregnancy and Pregnancy Adiposity
      on Offspring Size and Adiposity.
AB  - CONTEXT: Maternal adiposity and overnutrition, both before and during pregnancy,
      plays a key role in the subsequent development of obesity and metabolic outcomes
      in offspring. OBJECTIVE: We explored the hypothesis that maternal adiposity (pre
      pregnancy and at 26-28 weeks' gestation) and mid-pregnancy gestational weight
      gain (GWG) are independently associated with offspring size and adiposity in
      early childhood, and determined whether these effects are ethnicity dependent.
      DESIGN: In a prospective mother-offspring cohort study (N = 976, 56% Chinese, 26%
      Malay, and 18% Indian), we assessed the associations of offspring size (weight,
      length) and adiposity (subscapular and triceps skinfolds), measured at birth and
      age 6, 12, 18, and 24 mo, with maternal pre-pregnancy body mass index (ppBMI),
      mid-pregnancy GWG, and mid-pregnancy four-site skinfold thicknesses (triceps,
      biceps, subscapular, suprailiac). RESULTS: ppBMI and mid-pregnancy GWG were
      independently associated with postnatal weight up to 2 y and skinfold thickness
      at birth. Weight and subscapular and triceps skinfolds at birth increased by
      2.56% (95% confidence interval, 1.68-3.45%), 3.85% (2.16-5.57%), and 2.14% (0.54
      3.75%), respectively for every SD increase in ppBMI. Similarly, a one-SD increase
      in GWG increased weight and subscapular and triceps skinfolds at birth by 2.44%
      (1.66-3.23%), 3.28% (1.75-4.84%), and 3.23% (1.65-4.84%), respectively. ppBMI and
      mid-pregnancy suprailiac skinfold independently predicted postnatal skinfold
      adiposity up to 2 years of age, whereas only GWG predicted postnatal length. The
      associations of GWG with postnatal weight and length were present only among
      Chinese and Indians, but not Malays (P < .05 for interaction). CONCLUSIONS: ppBMI
      and GWG are independent modifiable factors for child size and adiposity up to 2
      years of age. The associations are ethnic-dependent, and underscore the
      importance of ethnic specific studies before generalizing the applicability of
      risk factors reported in other populations.

PMID- 26200237
TI  - Steroid Sex Hormones, Sex Hormone-Binding Globulin, and Diabetes Incidence in the
      Diabetes Prevention Program.
AB  - CONTEXT: Steroid sex hormones and SHBG may modify metabolism and diabetes risk,
      with implications for sex-specific diabetes risk and effects of prevention
      interventions. OBJECTIVE: This study aimed to evaluate the relationships of
      steroid sex hormones, SHBG and SHBG single-nucleotide polymorphisms (SNPs) with
      diabetes risk factors and with progression to diabetes in the Diabetes Prevention
      Program (DPP). DESIGN AND SETTING: This was a secondary analysis of a multicenter
      randomized clinical trial involving 27 U.S. academic institutions. PARTICIPANTS:
      The study included 2898 DPP participants: 969 men, 948 premenopausal women not
      taking exogenous sex hormones, 550 postmenopausal women not taking exogenous sex
      hormones, and 431 postmenopausal women taking exogenous sex hormones.
      INTERVENTIONS: Participants were randomized to receive intensive lifestyle
      intervention, metformin, or placebo. MAIN OUTCOMES: Associations of steroid sex
      hormones, SHBG, and SHBG SNPs with glycemia and diabetes risk factors, and with
      incident diabetes over median 3.0 years (maximum, 5.0 y). RESULTS: T and DHT were
      inversely associated with fasting glucose in men, and estrone sulfate was
      directly associated with 2-hour post-challenge glucose in men and premenopausal
      women. SHBG was associated with fasting glucose in premenopausal women not taking
      exogenous sex hormones, and in postmenopausal women taking exogenous sex
      hormones, but not in the other groups. Diabetes incidence was directly associated
      with estrone and estradiol and inversely with T in men; the association with T
      was lost after adjustment for waist circumference. Sex steroids were not
      associated with diabetes outcomes in women. SHBG and SHBG SNPs did not predict
      incident diabetes in the DPP population. CONCLUSIONS: Estrogens and T predicted
      diabetes risk in men but not in women. SHBG and its polymorphisms did not predict
      risk in men or women. Diabetes risk is more potently determined by obesity and
      glycemia than by sex hormones.

PMID- 26200239
TI  - Suicide by Cop.

PMID- 26200240
TI  - IASP Awards 2005.

PMID- 26200238
TI  - Human Chorionic Gonadotropin Partially Mediates Phthalate Association With Male
      and Female Anogenital Distance.
AB  - CONTEXT: Prenatal exposure to phthalates disrupts male sex development in
      rodents. In humans, the placental glycoprotein hormone human chorionic
      gonadotropin (hCG) is required for male development, and may be a target of
      phthalate exposure. OBJECTIVE: This study aimed to test the hypothesis that
      phthalates disrupt placental hCG differentially in males and females with
      consequences for sexually dimorphic genital development. DESIGN: The Infant
      Development and Environment Study (TIDES) is a prospective birth cohort. Pregnant
      women were enrolled from 2010-2012 at four university hospitals. PARTICIPANTS:
      Participants were TIDES subjects (n = 541) for whom genital and phthalate
      measurements were available and who underwent prenatal serum screening in the
      first or second trimester. MAIN OUTCOME MEASURES: Outcomes included hCG levels in
      maternal serum in the first and second trimesters and anogenital distance (AGD),
      which is the distance from the anus to the genitals in male and female neonates.
      RESULTS: Higher first-trimester urinary mono-n-butyl phthalate (MnBP; P = .01),
      monobenzyl phthalate (MBzP; P = .03), and mono-carboxy-isooctyl phthalate (P <
      .01) were associated with higher first-trimester hCG in women carrying female
      fetuses, and lower hCG in women carrying males. First-trimester hCG was
      positively correlated with the AGD z score in female neonates, and inversely
      correlated in males (P = 0.01). We measured significant associations of MnBP (P <
      .01), MBzP (P = .02), and mono-2-ethylhexyl phthalate (MEHP; P < .01) with AGD,
      after adjusting for sex differences. Approximately 52% (MnBP) and 25% (MEHP) of
      this association in males, and 78% in females (MBzP), could be attributed to the
      phthalate association with hCG. CONCLUSIONS: First-trimester hCG levels,
      normalized by fetal sex, may reflect sexually dimorphic action of phthalates on
      placental function and on genital development.

PMID- 26200242
TI  - International Association for Suicide Prevention.

PMID- 26200243
TI  - Instructions for Contributors.

PMID- 26200244
TI  - [Chronic Pelvic Pain Syndrome and Personality--Association of Somatic Symptoms
      and Psychic Structure].
AB  - BACKGROUND: Despite its high prevalence, little is known about the aetiology and
      maintenance of Chronic Pelvic Pain Syndrome (CPPS). CPPS is is considered to be a
      multi-causal syndrome with discomfort and pain in the pelvis. Recent literature
      suggests that psychosocial factors are important for understanding CPPS. For
      example, CPPS has been associated with deficits in mentalization and bonding
      experiences. Our study aims to characterize features of personality disorders
      according to DSM-IV and psychic structure according to OPD-2 in CPPS patients.
      Furthermore, we examine the association of personality aspects with urological
      symptoms (NIH Questionnaire) and pain perception (MPQ Questionnaire). MATERIALS &
      METHODS: Personality aspects were assessed in a total of 109 patients from our
      CPPS outpatient clinic using standardized questionnaires. To characterize CPPS
      patients, we compared the sample's scores with reference groups, mostly the
      general population. In addition, the associations between personality aspects and
      both the urologic symptoms and pain perception were assessed using correlations.
      Missing data were replaced using multiple imputation methods. RESULTS: Compared
      to reference values, we found 'experiencing emotions' and 'creating
      relationships' as specific deficits in CPPS patients. Furthermore, patients' self
      image (more dominant, higher depressive mood) differs from the general
      population. A higher pain perception was correlated with deficits in most
      personality aspects we measured. However, this was not the case for the severity
      of urological symptoms. DISCUSSION & CONCLUSION: Compared to the reference
      values, only a few personality aspects differed in CPPS patients but there was a
      correlational association between different personality traits and pain
      perception. Despite the extend of symptoms, pain perception is associated with
      difficulty (emotional ability) in dealing with emotions, self-management and
      relationships. These personality aspects should be taken into account when
      planning therapy.

PMID- 26200245
TI  - [Psychoeducation for Relatives of Persons with Depressive Disorders: A Focus
      Group Study on Information Demands].
AB  - BACKGROUND: Depressive disorders place a high burden on patients and their
      relatives. Psychoeducational groups for relatives may reduce relatives' burden
      and improve the course of disease in patients. To foster the development of
      psychoeducational interventions which meet relatives' needs, information demands
      in relatives of patients with depressive disorders were examined. METHODS: A
      qualitative study using 3 focus groups was conducted among adult relatives of
      patients with depressive disorders (N=17). Discussions were audio-taped,
      transcribed and analyzed using qualitative content analysis. RESULTS: Information
      demands are based on information gaps, emotional burden as well as strains in
      everyday living and were identified with regard to illness-specific (symptoms,
      course and etiology), treatment-specific (treatment options and health care
      system) and - as central aspects - interaction-specific issues (dealing with the
      patient, difficulties in everyday living and relationship problems) as well as
      support options for relatives themselves and self-care. CONCLUSIONS: Information
      brokerage within psychoeducational groups for relatives should consider the
      burden of relatives as well as strains in everyday living on which information
      demands are based. To consider interaction-specific issues, specific skills - e.
      g. in problemsolving - should be trained.

PMID- 26200246
TI  - [Out-Patient Psychosocial Cancer Counseling Centers and their Clients - Services
      Provided and Service Utilization by Patients and Patients' Relatives].
AB  - Psychosocial cancer counseling centers represent an increasingly important part
      of comprehensive psychosocial cancer care. Research on the services provided by
      those centers is sparse, however, as is research on person-, disease-, and
      treatment-related characteristics of their clients. Therefore, the present study
      analyzes the services provided by 26 psychosocial cancer counseling centers
      temporarily being funded by the German Cancer Aid as well as selected
      characteristics of their clients. Analyses are based on data collected during
      2011 by means of a documentation system specifically designed for the purposes of
      psychosocial cancer counseling. Testing focuses on whether cancer patients and
      cancer patients' relatives differ with respect to various characteristics and the
      services used. The results show that psychosocial and benefit counseling
      represent a major part of counseling services, followed by giving information and
      employing relaxation techniques. Clients seek counseling primarily in early
      phases of disease and treatment. Women with breast cancer are over-represented
      among clients. Analyses also reveal significant differences between cancer
      patients and patients' relatives. Psychotherapeutic interventions and grief
      counseling are more frequent in counseling relatives, whereas benefit counseling
      is more frequent in working with patients. The results emphasize the relevance of
      outpatient psychosocial cancer counseling. They may also help support initiatives
      aiming at establishing psychosocial cancer counseling targeted to the needs of
      each individual client. 

PMID- 26200247
TI  - Experiences of mobility device use over time: A multiple case study among very
      old Latvian women.
AB  - AIM: To explore the experiences over time of using mobility devices (MDs) among
      very old women in the context of everyday life in Latvia. METHODS: This study
      utilized a multiple case-study design that employed an explanatory mixed-methods
      approach. A combination of quantitative survey data on home and health and
      qualitative interview data for each participant were used to create three
      narratives to describe the experiences of MD use in everyday life over time,
      followed by a cross-case analysis. RESULTS: The three cases illustrate that very
      old women accept and use MDs due to walking difficulties and related needs. Over
      time, functional decline combined with physical environmental barriers and
      changes in their social networks limited the supportive role that available MDs
      could offer these women. CONCLUSIONS: The findings contribute to the
      understanding of the complexity of MD use in everyday life among very old women
      in Latvia and the need for different kinds of MDs. These findings illustrate the
      importance of considering the interaction between people's everyday life
      situation and their physical environment for their optimal use of MDs. This is
      important information for policy-makers who can optimize the services for old
      people in Latvia and support the need for occupational therapists' professional
      competence for the planning and development of MD provision.

PMID- 26200248
TI  - Disulfide-Functionalized Unimolecular Micelles as Selective Redox-Responsive
      Nanocarriers.
AB  - Redox-sensitive hyperbranched dendritic-linear polymers (HBDLPs) were prepared
      and stabilized individually as unimolecular micelles with diameters in the range
      25-40 nm. The high molecular weight (500-950 kDa), core-shell amphiphilic
      structures were synthesized through a combination of self-condensing vinyl
      copolymerization (SCVCP) and atom transfer radical polymerization (ATRP).
      Cleavable disulfide bonds were introduced, either in the backbone, or in pendant
      groups, of the hyperbranched core of the HBDLPs. By triggered reductive
      degradation, the HBDLPs showed up to a 7-fold decrease in molecular weight, and
      the extent of degradation was tuned by the amount of incorporated disulfides. The
      HBDLP with pendant disulfide-linked functionalities in the hyperbranched core was
      readily postfunctionalized with a hydrophobic dye, as a mimic for a drug. An
      instant release of the dye was observed as a response to a reductive environment
      similar to the one present intracellularly. The proposed strategy shows a facile
      route to highly stable unimolecular micelles, which attractively exhibit redox
      responsive degradation and cargo release properties. 

PMID- 26200250
TI  - Sensitivity of the cortical pitch onset response to height, time-variance, and
      directionality of dynamic pitch.
AB  - Event-related brain potentials (ERPs) demonstrate that human auditory cortical
      responses are sensitive to changes in static pitch as indexed by the pitch onset
      response (POR), a negativity generated at the initiation of acoustic periodicity.
      Yet, it is still unclear if this brain signature is sensitive to dynamic, time
      varying properties of pitch more characteristic of those found in naturalistic
      speech and music. Neuroelectric PORs were recorded in response to contrastive
      pitch patterns differing in their pitch height, time-variance, and directionality
      (i.e., rise vs. fall). Broadband noise followed by contiguous iterated rippled
      noise (producing salient pitch sweeps) was used to temporally separate neural
      activity coding the onset of acoustic energy from the onset of time-varying
      pitch. Analysis of PORs revealed distinct modulations in response latency that
      distinguished static from time-varying pitch contours (steady-state<dynamic) and
      pitch height (high<low). However, PORs were insensitive to the direction of pitch
      sweeps (rise=fall). Our findings suggest that the POR signature provides a useful
      neural index of auditory cortical pitch processing for some, but not all pitch
      evoking stimuli. 

PMID- 26200249
TI  - A giant local interneuron modulates the rhythmic activities of the antennal lobe
      in Pupae Drosophila.
AB  - In Drosophila, olfaction is tightly related to feeding and reproduction. There
      are three classes of neurons forming synapses in the olfactory circuit: the
      olfactory receptor neurons (ORNs), projection neurons (PNs), and local
      interneurons (LNs). Here, we showed that giant local interneurons named GLNs,
      which were different from the classical neurons in the olfactory circuits,
      displayed distinctive rhythmic activities in the dorsolateral side of antennal
      lobe (AL) in Drosophila Pupae. Anatomically, GLNs were much larger than
      ipsilateral LNs and extended arborizations throughout the AL.
      Electrophysiologically, GLN exhibited typical 4-phased rhythmic spontaneous
      membrane activities, and the surrounding cells were dye-coupled when biocytin was
      injected into the cell body of GLN. Our study demonstrated that spontaneous
      activities of GLNs correlated with that of LNs and PNs. After the GLNs were
      damaged, the membrane activities of ipsilateral LNs and PNs became smaller, but
      faster. By depressing the firing frequencies of PNs and LNs, GLNs modulated the
      synchronization of AL and might play an important role as a "modulator" in the
      local circuit. 

PMID- 26200251
TI  - ERK signaling mediates CaSR-promoted axon growth.
AB  - The extracellular calcium-sensing receptor (CaSR) is a G-protein coupled receptor
      that monitors the systemic extracellular free ionized calcium level ([Ca(2+)]o)
      in organs involved in systemic [Ca(2+)]o homeostasis. CaSR is widely expressed in
      the nervous system and its activation promotes axon and dendrite growth during
      development, but the mechanism by which it does this is not known. Here we show
      that enhanced axon growth and branching from cultured embryonic sympathetic
      neurons by activation of the endogenous CaSR depends on the presence of nerve
      growth factor (NGF). Our observation that activation of overexpressed CaSR
      promotes axon growth in NGF-free medium has enabled us to investigate CaSR
      downstream signaling contributing to axon growth in the absence of NGF signaling.
      We show that activation of overexpressed CaSR leads to activation of ERK1 and
      ERK2, and pharmacological inhibition of CaSR-dependent ERK1/ERK2 activation
      prevents CaSR-dependent axon growth. Analysis of axon growth from cultured
      neurons expressing deletion mutants of the CaSR cytoplasmic tail revealed that
      the region between alanine 877 and glycine 907 is required for promoting axon
      growth that is distinct from the high-affinity filamin-A binding site that has
      previously been implicated in ERK1/ERK2 activation. 

PMID- 26200252
TI  - Different cerebral plasticity of intrinsic and extrinsic hand muscles after
      peripheral neurotization in a patient with brachial plexus injury: A TMS and fMRI
      study.
AB  - Contralateral C7 (CC7) neurotization has been an important approach for brachial
      plexus injury (BPI). Patients can achieve relatively good grasping function
      driven by the proximal extrinsic hand muscle (flexor digitorum, FD) after CC7
      neurotization, whereas the thumb opposition function driven by the distal
      intrinsic muscle (abductor pollicis brevis, APB) is poor. The present study aimed
      to investigate the brain reorganization patterns of the recovery processes of
      intrinsic and extrinsic hand functions after repairing the median nerve by CC7
      neurotization. Transcranial magnetic stimulation (TMS) and functional magnetic
      resonance imaging (fMRI) were used to evaluate the cerebral plasticity in one BPI
      patient after CC7 neurotization. After the CC7 neurotization, the patient showed
      improvements in the paralyzed hand. Combination of TMS and fMRI investigations
      demonstrated different cortical reshaping patterns of APB and FD. It was also
      found that the activated cortical areas of FD were located in bilateral motor
      cortices, but the area of APB was only located in ipsilateral motor cortex. The
      cerebral plasticity procedure appeared to be different in the gross and fine
      motor function recovery processes. It provided a new perspective into the
      cerebral plasticity induced by CC7 neurotization. 

PMID- 26200254
TI  - Aerobic Bioremediation of PAH Contaminated Soil Results in Increased Genotoxicity
      and Developmental Toxicity.
AB  - The formation of more polar and toxic polycyclic aromatic hydrocarbon (PAH)
      transformation products is one of the concerns associated with the bioremediation
      of PAH-contaminated soils. Soil contaminated with coal tar (prebioremediation)
      from a former manufactured gas plant (MGP) site was treated in a laboratory scale
      bioreactor (postbioremediation) and extracted using pressurized liquid
      extraction. The soil extracts were fractionated, based on polarity, and analyzed
      for 88 PAHs (unsubstituted, oxygenated, nitrated, and heterocyclic PAHs). The PAH
      concentrations in the soil tested, postbioremediation, were lower than their
      regulatory maximum allowable concentrations (MACs), with the exception of the
      higher molecular weight PAHs (BaA, BkF, BbF, BaP, and IcdP), most of which did
      not undergo significant biodegradation. The soil extract fractions were tested
      for genotoxicity using the DT40 chicken lymphocyte bioassay and developmental
      toxicity using the embryonic zebrafish (Danio rerio) bioassay. A statistically
      significant increase in genotoxicity was measured in the unfractionated soil
      extract, as well as in four polar soil extract fractions, postbioremediation (p <
      0.05). In addition, a statistically significant increase in developmental
      toxicity was measured in one polar soil extract fraction, postbioremediation (p <
      0.05). A series of morphological abnormalities, including peculiar caudal fin
      malformations and hyperpigmentation in the tail, were measured in several soil
      extract fractions in embryonic zebrafish, both pre- and postbioremediation. The
      increased toxicity measured postbioremediation is not likely due to the 88 PAHs
      measured in this study (including quinones), because most were not present in the
      toxic polar fractions and/or because their concentrations did not increase
      postbioremediation. However, the increased toxicity measured postbioremediation
      is likely due to hydroxylated and carboxylated transformation products of the 3-
      and 4-ring PAHs (PHE, 1MPHE, 2MPHE, PRY, BaA, and FLA) that were most degraded. 

PMID- 26200255
TI  - In Situ Tissue Engineering of Functional Small-Diameter Blood Vessels by Host
      Circulating Cells Only.
AB  - Inflammation is a natural phase of the wound healing response, which can be
      harnessed for the in situ tissue engineering of small-diameter blood vessels
      using instructive, bioresorbable synthetic grafts. This process is dependent on
      colonization of the graft by host circulating cells and subsequent matrix
      formation. Typically, vascular regeneration in small animals is governed by
      transanastomotic cell ingrowth. However, this process is very rare in humans and
      hence less relevant for clinical translation. Therefore, a novel rat model was
      developed, in which cell ingrowth from the adjacent tissue is inhibited using
      Gore-Tex sheathing. Using this model, our aim here was to prove that functional
      blood vessels can be formed in situ through the host inflammatory response,
      specifically by blood-borne cells. The model was validated by implanting sex
      mismatched aortic segments on either anastomoses of an electrospun poly(E
      caprolactone) (PCL) graft, filled with fibrin gel, into the rat abdominal aorta.
      Fluorescent in situ hybridization analysis revealed that after 1 and 3 months in
      vivo, over 90% of infiltrating cells originated from the bloodstream, confirming
      the effective shielding of transanastomotic cell ingrowth. Using the validated
      model, PCL/fibrin grafts were implanted, either or not loaded with monocyte
      chemotactic protein-1 (MCP-1), and cell infiltration and tissue development were
      investigated at various key time points in the healing cascade. A phased healing
      response was observed, initiated by a rapid influx of inflammatory cells,
      mediated by the local release of MCP-1. After 3 months in vivo, the grafts
      consisted of a medial layer with smooth muscle cells in an oriented collagen
      matrix, an intimal layer with elastin fibers, and confluent endothelium. This
      study proves the regenerative potential of cells in the circulatory system in the
      setting of in situ vascular tissue engineering. 

PMID- 26200256
TI  - Sexual dysfunctions and lower urinary tract symptoms in ankylosing spondylitis.
AB  - AIM: To determine sexual dysfunctions and urinary symptoms in male ankylosing
      spondylitis (AS) patients and their association with various disease and patient
      factors. METHODS: In this prospective case control study conducted at a tertiary
      care teaching institution, 100 males with AS were compared to 100 controls using
      International Index of Erectile Function-15 (IIEF), International Prostate
      Symptom Score (IPSS), Hospital Anxiety and Depression Scale (HADS) and a global
      question for overall relationship with their partners. Bath AS Functional Index
      (BASFI), visual analogue scale pain scores, patient global assessment scale and
      Bath AS Disease Activity Index were also assessed in the AS group. Chi-square
      test, unpaired t-test and univariate and multivariate binary logistic regression
      analyses were used to analyze the data. RESULTS: Anxiety, depression, erectile
      dysfunction (ED), orgasmic dysfunction, intercourse dissatisfaction, overall
      sexual dissatisfaction, altered overall relationship with partner and lower
      urinary tract symptoms (LUTS) were significantly (P < 0.05) higher in the AS
      group as compared to controls. Sexual desire, severe LUTS and bothersome LUTS
      (quality of life score > 2) were not different (P = 0.76, 0.82 and 0.30
      respectively) between the two groups. ED was associated with anxiety, depression,
      longer disease duration, higher BASFI and higher age in AS patients (P = 0.02,
      0.001, 0.02, 0.003 and 0.001 respectively). CONCLUSIONS: AS is associated with
      higher incidence of sexual dysfunction in male patients. ED is associated with
      anxiety, depression, longer duration of disease, higher BASFI score and higher
      age in AS patients.

PMID- 26200257
TI  - Divalent Metal Ions Mg2+ and Ca2+ Have Distinct Effects on Protein Kinase A
      Activity and Regulation.
AB  - cAMP-dependent protein kinase (PKA) is regulated primarily in response to
      physiological signals while nucleotides and metals may provide fine-tuning. PKA
      can use different metal ions for phosphoryl transfer, yet some, like Ca(2+), do
      not support steady-state catalysis. Fluorescence Polarization (FP) and Surface
      Plasmon Resonance (SPR) were used to study inhibitor and substrate interactions
      with PKA. The data illustrate how metals can act differentially as a result of
      their inherent coordination properties. We found that Ca(2+), in contrast to
      Mg(2+), does not induce high-affinity binding of PKA to pseudosubstrate
      inhibitors. However, Ca(2+) works in a single turnover mode to allow for
      phosphoryl-transfer. Using a novel SPR approach, we were able to directly monitor
      the interaction of PKA with a substrate in the presence of Mg(2+)ATP. This allows
      us to depict the entire kinase reaction including complex formation as well as
      release of the phosphorylated substrate. In contrast to Mg(2+), Ca(2+) apparently
      slows down the enzymatic reaction. A focus on individual reaction steps revealed
      that Ca(2+) is not as efficient as Mg(2+) in stabilizing the enzyme:substrate
      complex. The opposite holds true for product dissociation where Mg(2+) easily
      releases the phospho-substrate while Ca(2+) traps both reaction products at the
      active site. This explains the low steady-state activity in the presence of
      Ca(2+). Furthermore, Ca(2+) is able to modulate kinase activity as well as
      inhibitor binding even in the presence of Mg(2+). We therefore hypothesize that
      the physiological metal ions Mg(2+) and Ca(2+) both play a role in kinase
      activity and regulation. Since PKA is localized close to calcium channels and may
      render PKA activity susceptible to Ca(2+), our data provide a possible mechanism
      for novel crosstalk between cAMP and calcium signaling. 

PMID- 26200259
TI  - Cutaneous Disseminated Emmonsiosis Due to Emmonsia pasteuriana in a Patient With
      Cytomegalovirus Enteritis.

PMID- 26200258
TI  - Pathological differences between white and grey matter multiple sclerosis
      lesions.
AB  - Multiple sclerosis (MS) is a debilitating disease characterized by demyelination
      of the central nervous system (CNS), resulting in widespread formation of white
      matter lesions (WMLs) and grey matter lesions (GMLs). WMLs are pathologically
      characterized by the presence of immune cells that infiltrate the CNS, whereas
      these immune cells are barely present in GMLs. This striking pathological
      difference between WMLs and GMLs raises questions about the underlying mechanism.
      It is known that infiltrating leukocytes contribute to the generation of WMLs;
      however, since GMLs show a paucity of infiltrating immune cells, their importance
      in GML formation remains to be determined. Here, we review pathological
      characteristics of WMLs and GMLs, and suggest some possible explanations for the
      observed pathological differences. In our view, cellular and molecular
      characteristics of WM and GM, and local differences within WMLs and GMLs (in
      particular, in glial cell populations and the molecules they express), determine
      the pathway to demyelination. Further understanding of GML pathogenesis,
      considered to contribute to chronic MS, may have a direct impact on the
      development of novel therapeutic targets to counteract this progressive
      neurological disorder. 

PMID- 26200260
TI  - Characterization of Sulfur Bonding in CdS:O Buffer Layers for CdTe-based Thin
      Film Solar Cells.
AB  - On the basis of a combination of X-ray photoelectron spectroscopy and synchrotron
      based X-ray emission spectroscopy, we present a detailed characterization of the
      chemical structure of CdS:O thin films that can be employed as a substitute for
      CdS layers in thin-film solar cells. It is possible to analyze the local chemical
      environment of the probed elements, in particular sulfur, hence allowing insights
      into the species-specific composition of the films and their surfaces. A detailed
      quantification of the observed sulfur environments (i.e., sulfide, sulfate, and
      an intermediate oxide) as a function of oxygen content is presented, allowing a
      deliberate optimization of CdS:O thin films for their use as alternative buffer
      layers in thin-film photovoltaic devices. 

PMID- 26200261
TI  - Nonoperative Management of Bilateral Adrenal Incidentalomas: The Value of
      Restraint.

PMID- 26200262
TI  - Are psychotropic medications associated with differences in baseline
      neurocognitive assessment scores for young athletes? A pilot study.
AB  - OBJECTIVES: Baseline and post-concussive neurocognitive testing is useful in
      managing concussed athletes. The Concussion in Sport Group has postulated that
      the use of psychotropic medications is a modifying factor in the management of
      sport-related concussion. About 7% of US adolescents are prescribed psychotropics
      in a given year. Our aim was to investigate whether psychotropic medication use
      or psychiatric illness is associated with differences in baseline neurocognitive
      test scores. METHODS: From 2007 to 2012, over 7000 athletes underwent pre
      participation baseline neurocognitive testing using the Immediate Post-Concussion
      Assessment and Cognitive Testing (ImPACT) battery. Following application of
      inclusion and exclusion criteria, athletes' self-reported medication lists were
      reviewed and: 1) classified as psychotropic or not and 2) subclassified. Group
      subclassification yielded: 1) use of any psychotropic medication, 2)
      psychostimulant use, 3) antidepressant use and 4) self-reported history of
      depression and/or anxiety without psychotropic use. Each group was matched, by
      sex, age, body mass index, education level and concussion history with athletes
      who were not reportedly prescribed psychotropic medications or did not report a
      depression/anxiety history, respectively. Each group's baseline ImPACT scores
      were compared to matched controls. RESULTS: The use of prescribed psychotropic
      medications without regard to subclass had no effect on baseline ImPACT composite
      scores among athletes ages 13-25. However, athletes reportedly prescribed
      psychostimulants displayed significantly lower visual motor speed scores (32.8 vs
      37.1, p = 0.030) and slower reaction times (0.65 vs 0.60, p = 0.044) than non
      users. In contrast, antidepressant users displayed significantly faster reaction
      times (0.58 vs 0.61, p = 0.029). Those reporting a history of depression/anxiety,
      not treated with psychotropics, displayed significantly lower visual memory (70.4
      vs 75.2, p = 0.010) and higher symptom scores (8.83 vs 4.72, p = 0.005).
      CONCLUSIONS: This pilot study suggests that self-reported psychotropic
      medications are associated with differences in baseline ImPACT test scores, which
      appear dependent on medication subclass. Our preliminary results support the
      inclusion of psychotropic medications, specifically psychostimulants and
      antidepressants, as well as history of depression/anxiety as potential concussion
      modifiers.

PMID- 26200265
TI  - Rearranging Detection of Gene Rearrangements.

PMID- 26200266
TI  - FDG-PET/CT as a Predictor of Outcome in EGFR-Mutant Non-Small-Cell Lung Cancer.

PMID- 26200267
TI  - Bevacizumab in Combination with Taxane versus Non-Taxane Containing Regimens for
      Advanced/Metastatic Nonsquamous Non-Small-Cell Lung Cancer: A Systematic Review.
AB  - BACKGROUND: In preclinical studies, the efficacy of the combination of
      antiangiogenic agents with chemotherapy seems to be dependent on the specific
      cytotoxic agent. We conducted a systematic review of the efficacy of bevacizumab
      in combination with taxane or non-taxane containing regimens for untreated,
      nonsquamous non-small-cell lung cancer patients. METHODS: An extensive search of
      published clinical trials was conducted from electronic databases (MEDLINE,
      EMBASE, and Cochrane) and meeting proceedings using relevant search criteria.
      Phase 2 and randomized trials reporting on the efficacy of bevacizumab combined
      with taxane or non-taxane regimens were selected. A systematic analysis of
      extracted data was performed using Comprehensive Meta-Analysis (Version 2.2)
      software. Clinical outcome in patients treated with taxane versus non-taxane
      regimen was compared using point estimates for weighted values of median overall
      survival, progression-free survival, and response rate. RESULTS: Twenty-nine
      studies reported between 2005 and 2015 were eligible. A total of 5890 patients
      (2767 and 3123 in the taxane and non-taxane groups, respectively) were included.
      The taxane and non-taxane groups were comparable in patient characteristics:
      median age, 62.8 versus 61.2 years; males, 57% versus 58%; adenocarcinomas, 83%
      versus 83%; stage IV, 87% versus 82%; performance status 0/1- 45/55% versus
      41/59%, respectively. The weighted median overall survival was 14.4 versus 13.7
      months (p = 0.5); progression-free survival was 6.93 versus 6.99 months (p =
      0.61); response rate was 41% versus 39% (p = 0.65) for taxane and non-taxane
      groups. CONCLUSIONS: The outcomes between taxane and non-taxane regimens when
      given in combination with bevacizumab for patients with nonsquamous non-small
      cell lung cancer are comparable.

PMID- 26200268
TI  - Crizotinib Associated with Ground-Glass Opacity Predominant Pattern Interstitial
      Lung Disease: A Retrospective Observational Cohort Study with a Systematic
      Literature Review.
AB  - BACKGROUND: Crizotinib, an oral tyrosine kinase inhibitor that targets anaplastic
      lymphoma kinase, has proven to offer sustained progression-free survival in
      anaplastic lymphoma kinase-rearranged non-small-cell lung cancers. Occurrence of
      severe interstitial lung disease (ILD) was one of the crucial adverse events
      reported in randomized clinical trials and case reports. METHODS: In September
      2011, we observed a crizotinib-associated ILD case. Following this index case, we
      reviewed the clinical and computed tomographic scan features of all patients
      treated with crizotinib in our department, between October 2010 and July 2013,
      comparing patients with and without ILD. A systematic literature review was
      performed. RESULTS: During this period, 29 patients were treated with crizotinib,
      five of whom developed ILD, in addition to the index case. Two types of adverse
      lung reactions may be observed in patients undergoing crizotinib therapy. The
      first is a severe, usually fatal, ILD that occurs during the first month of
      treatment (n = 1). The second is a less severe ILD, occurring later in time (n =
      5). It occurs gradually with only few clinical symptoms, but predominant ground
      glass opacities on computed tomography, along with an intensive lymphocytic
      alveolitis in bronchoalveolar lavage fluid. These cases had a longer response
      with a median progression-free survival duration at 19.9 months (17.9-23.5)
      compared with 6.2 months (1.2-13.6) for controls (p = 0.04). CONCLUSION: Forty
      nine cases of crizotinib-associated ILD have been identified by the systematic
      review of the literature, including our six cases. Two types of adverse lung
      reactions may be observed with different presentation, prognosis, and treatment.
      Their potential mechanisms should be clarified. Nine patients with the less
      severe form of ILD were safely retreated.

PMID- 26200269
TI  - Unique Genetic and Survival Characteristics of Invasive Mucinous Adenocarcinoma
      of the Lung.
AB  - INTRODUCTION: Invasive mucinous adenocarcinoma is a unique histologic subtype of
      lung cancer, and our knowledge of its genetic and clinical characteristics is
      rapidly evolving. Here, we present next- generation sequencing analysis of
      nucleotide variant and fusion events along with clinical follow-up in a series of
      lung mucinous adenocarcinoma. METHODS: We collected 72 mucinous adenocarcinomas
      from the United States and Korea. All had been previously assessed for KRAS and
      EGFR mutations. For KRAS wild-type cases (n = 30), we performed deep targeted
      next-generation sequencing for gene fusions and nucleotide variants and
      correlated survival and other clinical features. RESULTS: As expected, KRAS
      mutations were the most common alteration found (63% of cases); however, the
      distribution of nucleotide position alterations was more similar to that observed
      in gastrointestinal tumors than other lung tumors. Within the KRAS-negative
      cases, we found numerous potentially targetable gene fusions and mutations,
      including CD74-NRG1, VAMP2-NRG1, TRIM4-BRAF, TPM3-NTRK1, and EML4-ALK gene
      fusions and ERBB2, BRAF, and PIK3CA mutations. Unexpectedly, we found only two
      cases with TP53 mutation, which is much lower than observed in lung
      adenocarcinomas in general. The overall mutation burden was low in histologically
      confirmed mucinous adenocarcinomas from the public The Cancer Genome Atlas exome
      data set, regardless of smoking history, suggesting a link between TP53 status
      and mutation burden in mucinous tumors. There was no significant difference for
      recurrence-free survival between stage-matched mucinous and nonmucinous
      adenocarcinomas. It was notable that all recurrence sites were in the lungs for
      completely resected cases. CONCLUSIONS: Our data suggest that mucinous
      adenocarcinoma is typified by (1) frequent KRAS mutations and a growing list of
      gene fusions, but rare TP53 mutations, (2) a low mutation burden overall, and (3)
      a recurrence-free survival similar to stage-matched nonmucinous tumors, with
      recurrences limited to the lungs.

PMID- 26200270
TI  - Folate Receptor-Positive Circulating Tumor Cell Detected by LT-PCR-Based Method
      as a Diagnostic Biomarker for Non-Small-Cell Lung Cancer.
AB  - INTRODUCTION: To investigate the diagnostic performance of folate receptor
      positive circulating tumor cells in distinguishing non-small-cell lung cancer
      (NSCLC) from lung benign disease by using a novel ligand-targeted polymerase
      chain reaction (PCR) detection technique. METHODS: Circulating tumor cells were
      enriched from 3-ml peripheral blood by immunomagnetic depletion of leukocytes and
      then labeled with a conjugate of a tumor-specific ligand folic acid and a
      synthesized oligonucleotide. After washing off free conjugates, the stripped
      bound conjugates were analyzed by quantitative PCR. RESULTS: Seven hundred fifty
      six participants (473 patients with NSCLC, 227 patients with lung benign disease,
      and 56 healthy donors) were randomly assigned to a training set and a test set.
      The circulating tumor cell (CTC) levels in patients with NSCLC were significant
      higher than those with lung benign disease (p < 0.001) and healthy donors (p <
      0.001). Compared with carcinoembryonic antigen, neuron-specific enolase, and
      Cyfra21-1, CTCs displayed the highest area under the receiver operating
      characteristic curve (training set, 0.815; validation set, 0.813) in the
      diagnosis of NSCLC, with a markedly sensitivity (training set, 72.46%; validation
      set, 76.37%) and specificity (training set, 88.65%; validation set, 82.39%). The
      model combining CTCs with carcinoembryonic antigen, neuron-specific enolase, and
      Cyfra21-1 was more effective for the diagnosis of NSCLC than tumor makers alone
      (sensitivity and specificity in the training set, 84.21% and 83.91%; validation
      set, 88.78% and 87.36%, respectively). In addition, the CTC levels were higher in
      patients with stage III/IV NSCLC compared with those with stage I/II disease.
      CONCLUSION: Ligand-targeted PCR technique was feasible and reliable for detecting
      folate receptor-positive CTCs in patients with NSCLC, and CTC levels could be
      used as a useful biomarker for the diagnosis of NSCLC.

PMID- 26200271
TI  - Inhibiting MDM2-p53 Interaction Suppresses Tumor Growth in Patient-Derived Non
      Small Cell Lung Cancer Xenograft Models.
AB  - BACKGROUND: The tumor suppressor p53 is frequently inactivated in non-small cell
      lung cancer (NSCLC). Activation of the p53 pathway by inhibition of its negative
      regulator MDM2 may offer an attractive approach for NSCLC therapy. We evaluated
      the antitumor activity of the small-molecule MDM2 inhibitor RG7388 in patient
      derived xenograft (PDX) models of NSCLC. METHODS: We investigated the effect of
      RG7388 treatment on cell proliferation, cell cycle arrest, and apoptosis using a
      panel of human NSCLC cell lines (A549, H157, H1650, H1395, and H358) and PDX cell
      lines (human lung cell lines 12, 137, 277, and 196). PDX-bearing mice were used
      to test the therapeutic efficacy and pharmacodynamic effects of RG7388 treatment.
      RESULTS: We demonstrated that RG7388 promotes low nanomolar antiproliferative
      activity selectively in cell lines with wild-type p53 and p53 pathway activation,
      resulting in cell cycle arrest and apoptosis. In PDX models, oral administration
      of RG7388 led to potent dose-dependent and time-dependent activation of p53 and
      had a significant impact on p53 downstream targets. Daily treatment of RG7388 in
      mice at 50 and 80 mg/kg/day inhibited tumor growth in three wild-type p53 PDX
      models. Activation of the p53 pathway inhibited cell proliferation as observed by
      reduced Ki-67-positive cells in xenograft tumors. However, induction of apoptotic
      caspase activity was not observed in these tumors. Notably, RG7388 treatment
      remains effective in tumors lacking MDM2 amplification but expressing wild-type
      p53. CONCLUSIONS: MDM2 small-molecule inhibitor is effective in treating NSCLC
      tumors with wild-type p53, supporting further clinical investigation as a
      potential NSCLC therapy.

PMID- 26200272
TI  - Epigenetic Repression of CCDC37 and MAP1B Links Chronic Obstructive Pulmonary
      Disease to Lung Cancer.
AB  - INTRODUCTION: Lung cancer and chronic obstructive pulmonary disease (COPD) share
      environmental risk factors. COPD also increases the risk of lung cancer; however,
      the molecular mechanisms are unclear. METHODS: An epigenome-wide association
      study of lung tumors and cancer-free lung tissue (CFLT) pairs from non-small-cell
      lung cancer cases with (n = 18) or without (n = 17) COPD was conducted using the
      HumanMethylation450 beadchip (HM450K). COPD-associated methylation of top-ranked
      genes was confirmed in a larger sample set, independently validated, and their
      potential as sputum-based biomarkers was investigated. RESULTS: Methylation of
      CCDC37 and MAP1B was more prevalent in lung tumors from COPD than non-COPD cases
      [54 of 71 (76%) versus 20 of 46 (43%), p = 0.0013] and [48 of 71 (68%) versus 17
      of 46 (37%), p = 0.0035], respectively, after adjustment for age, sex, smoking
      status, and tumor histology. HM450K probes across CCDC37 and MAP1B promoters
      showed higher methylation in tumors than CFLT with the highest methylation seen
      in tumors from COPD cases (p < 0.05). These results were independently validated
      using The Cancer Genome Atlas data. CCDC37 methylation was more prevalent in
      sputum from COPD than non-COPD smokers (p < 0.005) from two cohorts. CCDC37 and
      MAP1B expression was dramatically repressed in tumors and CFLT from COPD than non
      COPD cases, p less than 0.02. CONCLUSIONS: The reduced expression of CCDC37 and
      MAP1B associated with COPD likely predisposes these genes to methylation that in
      turn, may contribute to lung cancer.

PMID- 26200273
TI  - Total Lesion Glycolysis in Positron Emission Tomography Can Predict Gefitinib
      Outcomes in Non-Small-Cell Lung Cancer with Activating EGFR Mutation.
AB  - INTRODUCTION: The purpose of this study was to evaluate the predictive role of
      quantitative metabolic parameters using total lesion glycolysis (TLG) in F-2
      fluoro-2-deoxyglucose-positron emission tomography/computed tomography for
      developing gefitinib resistance in epidermal growth factor receptor (EGFR)-mutant
      non-small-cell lung cancer (NSCLC) patients treated with first-line gefitinib.
      METHODS: A total of 75 NSCLC patients harboring activating EGFR mutation and
      receiving first-line gefitinib were analyzed. Whole-body F-2-fluoro-2
      deoxyglucose positron emission tomography/computed tomography scans were acquired
      before first-line gefitinib. The maximal standardized uptake value and TLG of all
      lesions were calculated. Maximal standardized uptake value and TLG were
      categorized using the tertile cutoff. Treatment outcomes were compared between
      groups. RESULTS: Overall response rate of gefitinib was 69.4%, and median
      progression-free survival (PFS) of gefitinib was 11.5 months. Overall response
      rates were similar between low, intermediate, and high TLG groups (68.0% versus
      76.0% versus 68.0%, p = 0.274). However, PFS significantly differed by TLG
      groups, and high TLG was associated with shorter PFS (7.2 months in high TLG;
      11.9 months in intermediate TLG; and 24.2 months in low, p < 0.001). Multivariate
      models adjusted for disease status and response to gefitinib showed that TLG was
      an independent predictive factor for PFS. TLG was also significantly associated
      with overall survival (p = 0.005). CONCLUSION: TLG can predict PFS and
      development of gefitinib resistance in EGFR-mutant NSCLC patients treated with
      first-line gefitinib. Baseline metabolic tumor burdens measured with TLG before
      first-line gefitinib will be of great help in predicting time to acquired
      resistance.

PMID- 26200274
TI  - Patterns of Disease Recurrence after SABR for Early Stage Non-Small-Cell Lung
      Cancer: Optimizing Follow-Up Schedules for Salvage Therapy.
AB  - INTRODUCTION: Stereotactic ablative radiotherapy is a guideline-recommended
      treatment for early stage non-small-cell lung cancer. We report on incidence and
      salvage of local recurrences (LR) and second primary lung cancers (SPLC) in a
      large series of patients with long-term follow-up, to generate data for evidence
      based follow-up regimens. METHODS: We excluded all patients with double tumors,
      TNM-stages other than T1-T2N0M0, biologically effective dose less than 100 Gy10
      and previous treatment for the index tumor from our institutional database. LR
      was defined as recurrence in/adjacent to the planning target volume. A diagnosis
      of SPLC was determined using criteria described by Martini et al. RESULTS: The
      855 patients included had a median follow-up of 52 months. Forty-six patients
      developed LR after a median of 22 months (range 7-87 months). Actuarial local
      control rates at 3 and 5 years were 92.4% and 90.9%, respectively. Fifty-four
      percent had isolated LR and 13% had LR in combination with regional recurrences.
      Ten patients underwent radical salvage treatment; surgery (N = 6), high-dose
      radiotherapy (N = 3), or chemoradiation (N = 1). Median overall survival
      following LR was 13 months, but it was 36 months in patients who underwent
      radical salvage. A SPLC was diagnosed in 79 patients, after a median interval of
      34 months. Actuarial cumulative incidences of SPLC at 3 and 5 years were 11.7%
      and 16.7%, respectively. Radical salvage for SPLC was performed in 63 patients
      (80%). CONCLUSIONS: Both the timing of LR and persistent risk of SPLC serve as
      rationale for long-term follow-up using computed tomography scans in patients fit
      enough to undergo any radical treatment.

PMID- 26200276
TI  - A Predictive Model for Lymph Node Involvement with Malignancy on PET/CT in Non
      Small-Cell Lung Cancer.
AB  - INTRODUCTION: Accurate assessment of lymph node (LN) involvement with malignancy
      is critical to staging and management of non-small-cell lung cancer. The goal of
      this retrospective study was to determine the tumor and imaging characteristics
      independently associated with malignant involvement of LNs visualized on positron
      emission tomography/computed tomography (PET/CT). METHODS: From 2002 to 2011, 172
      patients with newly diagnosed non-small-cell lung cancer underwent PET/CT within
      31 days before LN biopsy. Among these patients, 504 anatomically defined,
      pathology-confirmed LNs were visualized on PET/CT. Logistic regression analysis
      was used to determine the associations between nodal involvement with malignancy
      and several clinical and imaging variables, including tumor histology, tumor
      grade, LN risk category in relation to the primary tumor location, pathologic
      findings from additional biopsied LNs, interval between PET/CT and biopsy,
      primary tumor largest dimension, primary tumor standardized uptake value
      (SUVmax), LN short-axis dimension, and LN SUVmax. RESULTS: On univariate
      analysis, adenocarcinoma histology (p = 0.010), high LN risk category (p <
      0.001), larger LN short-axis dimension (p < 0.001), and higher LN SUVmax (p <
      0.001) all correlated with nodal involvement. On multivariate analysis,
      adenocarcinoma histology (p = 0.003), high LN risk category (p = 0.005), and
      higher LN SUVmax (p < 0.001) correlated with nodal involvement, whereas LN short
      axis dimension was no longer statistically significant (p = 0.180). A nomogram
      developed for clinical application based on this analysis had excellent
      concordance between predicted and observed results (concordance index, 0.95).
      CONCLUSION: Adenocarcinoma histology, higher LN SUVmax, and higher LN risk
      category independently correlate with nodal involvement with malignancy and may
      be used in a model to accurately predict the risk of a node's involvement with
      malignancy.

PMID- 26200275
TI  - Outcomes after Stereotactic Body Radiotherapy versus Limited Resection in Older
      Patients with Early-Stage Lung Cancer.
AB  - BACKGROUND: Limited resection and stereotactic body radiotherapy (SBRT) have
      emerged as treatment options for older patients with early-stage non-small-cell
      lung cancer (NSCLC), who are not good candidates for lobectomy. METHODS: We used
      the Surveillance, Epidemiology and End Results-Medicare registry to identify
      patients older than 65 years with stage I to II NSCLC and negative lymph nodes
      treated with SBRT versus limited resection. We fitted a propensity score model
      predicting the use of SBRT and compared adjusted overall survival of patients
      treated with SBRT versus limited resection. Secondary analyses stratified the
      sample by type of limited resection (wedge versus segmentectomy), age (<=75
      versus >75 years), and tumor size (<3 versus >=3 cm). We also compared rates of
      surgical complications and SBRT-related toxicity in the two groups. RESULTS: We
      identified 2243 patients of which 362 (16%) patients received SBRT. SBRT-treated
      patients were older, had higher comorbidity scores, and had larger tumors (p <
      0.001 for all comparisons). Adjusted analyses showed no differences in survival
      (hazard ratio [HR], 1.19; 95% confidence interval [CI], 0.97-1.47) among patients
      treated with SBRT versus limited resection. Although survival of patients who
      underwent SBRT versus wedge resection was not different (HR, 1.22; 95% CI, 0.98
      1.52), SBRT was associated with worse outcomes when compared with segmentectomy
      (HR, 1.55; 95% CI, 1.18-2.03). Adverse events were most often respiratory and
      more frequent in the patients treated with limited resection (28% versus 14%, p <
      0.001). CONCLUSION: SBRT is better tolerated and associated with similar survival
      when compared with wedge resection but not with segmentectomy in older patients
      with node-negative NSCLC.

PMID- 26200277
TI  - Nomograms Predict Overall Survival for Patients with Small-Cell Lung Cancer
      Incorporating Pretreatment Peripheral Blood Markers.
AB  - BACKGROUND: We sought to build prognostic nomograms and identify novel prognostic
      factors in small-cell lung cancer (SCLC) incorporating both clinical data and
      peripheral blood markers. METHODS: We analyzed 938 patients with SCLC (555
      extensive stage SCLC [ES-SCLC] and 383 limited stage SCLC [LS-SCLC]) diagnosed
      between 1997 and 2012 from a single institution. We investigated the prognostic
      value of pretreatment neutrophil to lymphocyte ratio, platelet to lymphocyte
      ratio, red cell distribution width, hemoglobin, and other clinicopathological
      factors. Cox proportional hazards models determined the effects of multiple
      factors on overall survival (OS). Two nomograms were developed to predict median
      survival and 6- and 12-month OS for ES-SCLC, and 1- and 2-year OS for LS-SCLC.
      RESULTS: In ES-SCLC, the multivariate Cox model identified neutrophil to
      lymphocyte ratio and red cell distribution width as significant prognostic
      factors for OS independent of age, Eastern Cooperative Oncology Group performance
      score, chest radiation, chemotherapy, liver metastases, and numbers of metastatic
      sites. In LS-SCLC, significant prognostic variables included platelet to
      lymphocyte ratio, age, smoking cessation, chest radiation, chemotherapy, surgery,
      and prophylactic cranial irradiation. The two nomograms show good accuracy in
      predicting OS, with a concordance index of 0.73 in both ES- and LS-SCLC.
      CONCLUSION: The two nomograms incorporating hematological markers could more
      accurately predict individualized survival probability of SCLC than the existing
      models.

PMID- 26200278
TI  - Cabazitaxel Versus Topotecan in Patients with Small-Cell Lung Cancer with
      Progressive Disease During or After First-Line Platinum-Based Chemotherapy.
AB  - INTRODUCTION: Patients with small-cell lung cancer (SCLC) typically respond well
      to initial chemotherapy. However, relapse invariably occurs, and topotecan, the
      only approved second-line treatment option, has limited efficacy. Taxanes have
      activity in SCLC, and cabazitaxel is a second-generation taxane with potential
      for enhanced activity in chemorefractory malignancies. METHODS: Patients with
      SCLC who relapsed after initial platinum-based chemotherapy were randomly
      assigned to receive cabazitaxel 25 mg/m every 21 days or topotecan 1.5 mg/m on
      days 1-5 every 21 days. Two patient subgroups, defined by chemosensitive and
      chemo-resistant/refractory disease, were assessed in combination and separately.
      RESULTS: The safety profile of cabazitaxel and topotecan was consistent with
      previous studies, and despite considerable toxicity in both arms, no new safety
      concerns were identified. Patients receiving cabazitaxel had inferior progression
      free survival compared with topotecan (1.4 versus 3.0 months, respectively; two
      sided p < 0.0001; hazard ratio = 2.17, 95% confidence interval = 1.563-3.010),
      and results were similar in both the chemosensitive and chemorefractory
      subgroups. No complete responses were observed in either arm, and no partial
      responses were observed in the cabazitaxel group. The partial response rate in
      the topotecan arm was 10%. Median overall survival was 5.2 months in the
      cabazitaxel arm and 6.8 months in the topotecan arm (two-sided p = 0.0125; hazard
      ratio = 1.57, 95% confidence interval = 1.10-2.25). CONCLUSION: Cabazitaxel, a
      next-generation taxane, had inferior efficacy when compared with standard-dose
      topotecan in the treatment of relapsed SCLC. Topotecan remains a suboptimal
      therapy, and continued efforts to develop improved second-line treatments are
      warranted.

PMID- 26200279
TI  - A Case of Pulmonary Squamous Cell Carcinoma Revealed Ground Glass Opacity on
      Computed Tomography.

PMID- 26200280
TI  - 18F-Sodium Fluoride PET-CT for the Assessment of Brain Metastasis from Lung
      Adenocarcinoma.

PMID- 26200281
TI  - Dose-Escalated Stereotactic Body Radiotherapy (SBRT) as a Salvage Treatment for
      Two Cases with Relapsed Peripheral Lung Cancer After Initial SBRT.

PMID- 26200282
TI  - Crizotinib Improves Osteoarthritis Symptoms in a ROS1-Fusion Advanced Non-Small
      Cell Lung Cancer Patient.

PMID- 26200283
TI  - A Case of Squamous Cell Carcinoma Harboring an EML4-ALK Rearrangement that Was
      Unsuccessfully Treated with the ALK Inhibitor Alectinib.

PMID- 26200284
TI  - Bevacizumab in Combination with Chemotherapy or Molecularly Targeted Agents for
      Non-Small-Cell Lung Cancer with Brain Metastases.

PMID- 26200285
TI  - Incidental Findings Implying an Inherited Cancer Syndrome from Advanced Tumor
      Sequencing.

PMID- 26200286
TI  - In Response.

PMID- 26200287
TI  - Challenges in Bevacizumab and Gefitinib Combination Therapy for Patients with Non
      Small-Cell Lung Cancer.

PMID- 26200288
TI  - Challenges in Bevacizumab and Gefitinib Combination Therapy for Patients with Non
      Small-Cell Lung Cancer.

PMID- 26200289
TI  - Rare versus Artifactual EGFR Mutations.

PMID- 26200290
TI  - Reply to Rare Versus Artifactual EGFR Mutations.

PMID- 26200291
TI  - Maintenance Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase
      Inhibitor after First-Line Chemotherapy in Mutation-Positive Non-Small-Cell Lung
      Cancer.

PMID- 26200292
TI  - Reply: To PMID 25546556.

PMID- 26200293
TI  - Searching for ROS1 Rearrangements in Lung Cancer by Fluorescent In Situ
      Hybridization: The Importance of Probe Design.

PMID- 26200294
TI  - In Response.

PMID- 26200295
TI  - Lipophilic ruthenium salen complexes: incorporation into liposome bilayers and
      photoinduced release of nitric oxide.
AB  - A new lipophilic Ru salen complex with cholesterol groups can be efficiently
      incorporated into liposome bilayers, allowing the photoinduced release of nitric
      oxide (NO) and the membrane transport of NO to coexisting liposomes. 

PMID- 26200296
TI  - DAMPs and influenza virus infection in ageing.
AB  - Influenza A virus (IAV) is a serious global health problem worldwide due to
      frequent and severe outbreaks. IAV causes significant morbidity and mortality in
      the elderly population, due to the ineffectiveness of the vaccine and the
      alteration of T cell immunity with ageing. The cellular and molecular link
      between ageing and virus infection is unclear and it is possible that damage
      associated molecular patterns (DAMPs) may play a role in the raised severity and
      susceptibility of virus infections in the elderly. DAMPs which are released from
      damaged cells following activation, injury or cell death can activate the immune
      response through the stimulation of the inflammasome through several types of
      receptors found on the plasma membrane, inside endosomes after endocytosis as
      well as in the cytosol. In this review, the detriment in the immune system during
      ageing and the links between influenza virus infection and ageing will be
      discussed. In addition, the role of DAMPs such as HMGB1 and S100/Annexin in
      ageing, and the enhanced morbidity and mortality to severe influenza infection in
      ageing will be highlighted. 

PMID- 26200297
TI  - Open Access: Opportunity and Awareness.

PMID- 26200298
TI  - Reviewing the Literature: Essential First Step in Research, Quality Improvement,
      and Implementation of Evidence-Based Practice.
AB  - This article provides nursing professional development specialists with a concise
      resource on conducting literature reviews: the essential first step of a research
      project, quality improvement initiative, or the implementation of evidence-based
      practice. The literature review cannot be overlooked because it sets the
      foundation for an investigative project's ethical implementation and subsequent
      success. Conducting a literature review may seem overwhelming for the novice, but
      these fears can be overcome with knowledge and practical assistance. 

PMID- 26200299
TI  - Simulation Improves Nurses' Adherence With Stroke Quality Measures.
AB  - Simulation engages nurses in learning within a safe environment. This teaching
      method evaluates both skill and knowledge attainment, but evaluating the impact
      on patient outcomes after a simulation training event is limited. This article
      reviews the impact simulation training had on nurses' adherence to stroke quality
      measures. 

PMID- 26200300
TI  - Developing a Comprehensive Critical Care Orientation Program for Graduate Nurses.
AB  - In 2014, newly graduated nurses are welcomed and recruited to practice in
      critical care, and hiring trends in hospitals support a demand for newly
      graduated nurses. At a 501-bed, quaternary care, academic medical center located
      in the Rocky Mountain region, an orientation program was formalized to prepare
      newly graduated nurses for critical care practice. The critical care clinical
      orientation program presented utilizes a dynamic approach that includes didactic
      study, case study integration, a clinical staging program, active preceptor
      development, and care-based simulation exercises. The purpose of this article is
      to describe the clinical orientation program developed in critical care, which
      augments an accredited New Graduate Nurse Residency Program. 

PMID- 26200301
TI  - Improving Nurses' Knowledge of Heart Failure.
AB  - The purpose of this study was to examine the difference in cardiac nurses'
      knowledge and perceived competency in the care of patients with heart failure
      (HF). Fifty-seven cardiac RNs completed the Advanced Heart Failure Clinical
      Competency Survey as a pretest/posttest measure. Each participant attended a 30
      minute HF education session. Nurses' knowledge of HF significantly improved from
      25.60 (SD = 2.92) pretest score to 27.30 (SD = 3.11) posttest score. The
      difference between the two means is statistically significant at the .001 level
      (t = -4.2, df = 56). 

PMID- 26200302
TI  - Lessons Learned: Accessing the Voice of Nurses to Improve a Novice Nurse Program.
AB  - A novice nurse program was developed to address the need for educational and
      clinical support for entry-level nurses in a community hospital setting. A focus
      group was used to assess the novice nurses' perception of the program and to
      synthesize lessons learned. Nursing professional development specialists are
      advised to access the voice of novice nurse participants to meaningfully evaluate
      and further develop residency programs. 

PMID- 26200303
TI  - Content Integrity, Conflict of Interest, and Commercial Support: Defining and
      Operationalizing the Terms.
AB  - One of the hallmarks of quality continuing education developed using
      accreditation criteria is content integrity. Components of content integrity
      include identifying, resolving, and disclosing conflict of interest; ensuring
      content is based on the best available evidence; managing commercial support (if
      applicable); and presenting the educational activity free of promotion or bias.
      This article explores content integrity, conflict of interest, and commercial
      support. Understanding and being able to operationalize these concepts will
      enable providers to offer high-quality educational activities that promote the
      professional development of nurses and/or improve the quality of patient care. 

PMID- 26200304
TI  - Population-Based Nursing Competency Development.
AB  - A collaborative process that included geriatric assessments and audits was
      utilized to develop geriatric nursing competencies that were evidence based,
      relevant to the specific needs of the older adults cared for at a facility, and
      inclusive of appropriate resources for any staff nurse caring for an older adult
      anywhere in the hospital. This method of competency development could be utilized
      in the development of other population-specific nursing competencies. 

PMID- 26200306
TI  - Results From the National Council of State Boards of Nursing's Transition-to
      Practice Study, Part 2.

PMID- 26200305
TI  - 73 is the New 65: Educating and Retaining the Aging Nursing Workforce.

PMID- 26200307
TI  - Interprofessional Education: Implications for Nursing Professional Development
      Practice.

PMID- 26200309
TI  - Overcoming Barriers.
AB  - Dr. Neal-Boylan's program of scholarship has always focused on nurse workforce
      issues. She recently published two books related to how nurses work. One (The
      Nurse's Reality Gap: Overcoming Barriers Between Academic Achievement and
      Clinical Success; Neal-Boylan, 2013) focused on the experience of new graduates
      from baccalaureate, master's, and doctoral programs. The second book, The Nurse's
      Reality Shift: Using Our History to Transform Our Future (Neal-Boylan, 2014),
      focuses on the problems nursing continues to face throughout our history and has
      failed to correct.

PMID- 26200310
TI  - Architectural Design for Orientation: Finding a Common Ground for Success.

PMID- 26200312
TI  - Uncovering a Role for SK2 in Angelman Syndrome.
AB  - Angelman syndrome is a severe neurodevelopmental disorder caused by mutations in
      UBE3A. Sun et al. (2015) report SK2 as a UBE3A substrate and provide insight into
      the molecular mechanisms that might underlie impaired neuronal function in
      individuals affected by Angelman syndrome.

PMID- 26200317
TI  - Dynamics of Magnesite Formation at Low Temperature and High pCO2 in Aqueous
      Solution.
AB  - Magnesite precipitation from aqueous solution, despite conditions of
      supersaturation, is kinetically hindered at low temperatures for reasons that
      remain poorly understood. The present study examines the products of Mg(OH)2
      reaction in solutions saturated with supercritical CO2 at high pressures (90 and
      110 atm) and low temperatures (35 and 50  degrees C). Solids characterization
      combined with in situ solution analysis reveal that the first reaction products
      are the hydrated carbonates hydromagnesite and nesquehonite, appearing
      simultaneously with brucite dissolution. Magnesite is not observed until it
      comprises a minor product at 7 days reaction at 50  degrees C. Complete
      transition to magnesite as the sole product at 35  degrees C (135 days) and at a
      faster rate at 50  degrees C (56 days) occurs as the hydrated carbonates slowly
      dissolve under the slightly acidic conditions generated at high pCO2. Such a
      reaction progression at high pCO2 suggests that over long term the hydrated Mg
      carbonates functioned as intermediates in magnesite formation. These findings
      highlight the importance of developing a better understanding of the processes
      expected to occur during CO2 storage. They also support the importance of
      integrating magnesite as an equilibrium phase in reactive transport calculations
      of the effects of CO2 sequestration on geological formations at long time scale. 

PMID- 26200318
TI  - Synthesis and chemistry of the open-cage cobaltaheteroborane cluster [{(eta(5)
      C5Me5)Co}2B2H2Se2]: a combined experimental and theoretical study.
AB  - Reaction of [(eta(5)-C5Me5)CoCl]2 with a two-fold excess of [LiBH4.thf] followed
      by heating with an excess of Se powder produces the dicobaltaselenaborane species
      [{(eta(5)-C5Me5)Co}2B2H2Se2], , in good yield. The geometry of resembles a nido
      pentagonal [Co2B2Se2] bipyramid with a missing equatorial vertex. It can
      alternatively be seen as an open cage triple-decker cluster. Isolation of permits
      its reaction with [Fe2(CO)9] to give heterometallic diselenametallaborane
      [{(eta(5)-C5Me5)Co}Fe(CO)3B2H2Se2], . The geometry of is similar to that of with
      one of the [(eta(5)-C5Me5)Co] groups replaced by the isolobal, two-electron
      fragment [Fe(CO)3]. Both new compounds have been characterized by mass
      spectrometry, and by (1)H, (11)B and (13)C NMR spectroscopy. The structural
      architectures have been unequivocally established by crystallographic analysis.
      In addition, density functional theory calculations were performed to investigate
      the bonding and electronic properties. The large HOMO-LUMO gaps computed for both
      clusters are consistent with their thermodynamic stability. Natural bond order
      calculations predict the absence of metal-metal bonding interaction. 

PMID- 26200319
TI  - Rigid shells enhance survival of gekkotan eggs.
AB  - The majority of lizards and snakes produce permeable parchment-shelled eggs that
      require high moisture conditions for successful embryonic development. One clade
      of gekkotan lizards is an exception; females produce relatively impermeable rigid
      shelled eggs that normally incubate successfully under low moisture conditions. I
      tested the hypothesis that the rigid-shell increases egg survival during
      incubation, but only under low moisture conditions. To test this hypothesis, I
      incubated rigid-shelled eggs of Chondrodactylus turneri under low and under high
      moisture conditions. Eggs were incubated with parchment-shelled eggs of
      Eublepharis macularius to insure that incubation conditions were suitable for
      parchment-shelled eggs. Chondrodactylus turneri eggs had very high survival
      (>90%) when they were incubated under low moisture conditions. In contrast, eggs
      incubated under high moisture conditions had low survival overall, and lower
      survival than those of the parchment-shelled eggs of E. macularius. Mortality of
      C. turneri and E. macularius eggs incubated under high moisture conditions was
      the result of fungal infection, a common source of egg mortality for squamates
      under laboratory and field conditions. These observations document high survival
      of rigid-shelled eggs under low moisture conditions because eggs escape from
      fungal infection. Highly mineralized rigid shells also make egg survival
      independent of moisture availability and may also provide protection from small
      invertebrates in nature. Enhanced egg survival could thus compensate for the low
      reproductive output of gekkotans that produce rigid-shelled eggs.

PMID- 26200320
TI  - Highly Stable Operation of Metal Oxide Nanowire Transistors in Ambient Humidity,
      Water, Blood, and Oxygen.
AB  - The capability for robust operation of nanoscale transistors under harsh
      environments is equally important as their operating parameters such as high on
      currents, high mobility, and high sensing selectivity. For electronic/biomedical
      applications, in particular, transistor operation must be stable under diverse
      conditions including ambient humidity, water, blood, and oxygen. Here we
      demonstrate the use of a self-assembled monolayer of octadecylphosphonic acid (OD
      PA) to passivate a functionalized nanowire transistor, allowing the device to
      operate consistently in such environments. In contrast, without passivation, the
      characteristics (especially the threshold voltage) of identical nanowire
      transistors were dramatically altered under these conditions. Furthermore, the OD
      PA-passivated transistor shows no signs of long-term stability deterioration and
      maintains equally high sensing selectivity to light under the harsh environments
      because of OD-PA's optical transparency. These results demonstrate the
      suitability of OD-PA passivation methods for fabricating commercial
      nanoelectronics. 

PMID- 26200321
TI  - Look to LSHSS for Cutting-Edge Research.

PMID- 26200322
TI  - Enhancement of Triboluminescence in the Presence of CO2 by Sliding between Silica
      and Yttria-Stabilized Zirconia.
AB  - Triboluminescence (TL) has gained increasing attention in the past two decades
      due to its potential for many applications such as an in situ damage sensor, X
      ray source, spectroscopic probe, and optical switch. So far the mechanisms by
      which TL is excited are not well understood. We have investigated the TL emitted
      during the sliding contact between silica wafer and YSZ (yttria-stabilized
      zirconia) wafers in CO2 gas, ambient air, and vacuum. We discovered that the mean
      intensity of photons emitted in CO2 gas is nearly a hundred times stronger than
      that in air. TL induced in the sliding experiment is proposed to be due to a
      combination of chemical luminescence, impurities and vacancies luminescence. In
      addition, the intensity of the light emission of YSZ may be controlled by
      changing the concentration of CO2 gas. 

PMID- 26200323
TI  - Universal Fluorescence Biosensor Platform Based on Graphene Quantum Dots and
      Pyrene-Functionalized Molecular Beacons for Detection of MicroRNAs.
AB  - A novel biosensor platform was developed for detection of microRNAs (miRNAs)
      based on graphene quantum dots (GQDs) and pyrene-functionalized molecular beacon
      probes (py-MBs). Pyrene was introduced to trigger specifically fluorescence
      resonance energy transfer (FRET) between GQDs and fluorescent dyes labeled on py
      MBs, and the unique fluorescent intensity change produced a novel signal for
      detection of the target. The platform realized detection of miRNAs in a wide
      range from 0.1 nM to 200 nM with great discrimination abilities, as well as
      multidetection of different kinds of miRNAs, which paved a brand new way for
      miRNA detection based on GQDs. 

PMID- 26200324
TI  - Next Step toward Optimization of GRP Receptor Avidities: Determination of the
      Minimal Distance between BBN(7-14) Units in Peptide Homodimers.
AB  - As the gastrin releasing peptide receptor (GRPR) is overexpressed on several
      tumor types, it represents a promising target for the specific in vivo imaging of
      these tumors using positron emission tomography (PET). We were able to show that
      PESIN-based peptide multimers can result in substantially higher GRPR avidities,
      highly advantageous in vivo pharmacokinetics and tumor imaging properties
      compared to the respective monomers. However, the minimal distance between the
      peptidic binders, resulting in the lowest possible system entropy while enabling
      a concomitant GRPR binding and thus optimized receptor avidities, has not been
      determined so far. Thus, we aimed here to identify the minimal distance between
      two GRPR-binding peptides in order to provide the basis for the development of
      highly avid GRPR-specific PET imaging agents. We therefore synthesized dimers of
      the GRPR-binding bombesin analogue BBN(7-14) on a dendritic scaffold, exhibiting
      different distances between both peptide binders. The homodimers were further
      modified with the chelator NODAGA, radiolabeled with (68)Ga, and evaluated in
      vitro regarding their GRPR avidity. We found that the most potent of the newly
      developed radioligands exhibits GRPR avidity twice as high as the most potent
      reference compound known so far, and that a minimal distance of 62 bond lengths
      between both peptidic binders within the homodimer can result in concomitant
      peptide binding and optimal GRPR avidities. These findings answer the question as
      to what molecular design should be chosen when aiming at the development of
      highly avid homobivalent peptidic ligands addressing the GRPR. 

PMID- 26200325
TI  - Investigation of the surfactant type and concentration effect on the retention
      factors of glutathione and its analogues by micellar electrokinetic
      chromatography.
AB  - In the present study, a micellar electrokinetic chromatographic method was used
      to determine the retention factors of hydrophilic monomeric and homodimeric forms
      of glutathione analogues. Ionic-liquid-based surfactant, 1-tetradecyl-3
      methylimidazolium chloride, as well as cetyltrimethylammonium bromide and
      phosphate buffer (pH 7.4) were employed in the experiments. Since the studied
      peptides possess a negative charge under physiological conditions, it is expected
      that the peptides interact with the oppositely charged 1-tetradecyl-3
      methylimidazolium chloride and cetyltrimethylammonium bromide micelles via
      hydrophobically assisted electrostatic forces. The dependence of the retention
      factor on the micellar concentration of 1-tetradecyl-3-methylimidazolium chloride
      and cetyltrimethylammonium bromide is nonlinear and the obtained curves converge
      to a limiting value. The retention factor values of GSH analogues were in the
      range of 0.36-2.22 for glutathione analogues and -1.21 to 0.37 for glutathione
      when 1-tetradecyl-3-methylimidazolium chloride was used. When
      cetyltrimethylammonium bromide was employed, the retention factor values were in
      the range of 0.27-2.17 for glutathione analogues and -1.22 to 0.06 for
      glutathione. If sodium dodecyl sulfate was used, the retention factor values of
      glutathione analogues with carnosine moiety were in the range of -1.54 to 0.38. 

PMID- 26200326
TI  - Facile preparation of the N-acetyl-glucosaminylated asparagine derivative with
      TFA-sensitive protecting groups useful for solid-phase glycopeptide synthesis.
AB  - In this study, a novel N-acetyl-glucosaminylated asparagine derivative was
      developed. This derivative carried TFA-sensitive protecting groups and was
      derived from commercially available compounds only in three steps. It was
      applicable to the ordinary 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase
      peptide synthesis (SPPS) method, and the protecting groups on the carbohydrate
      moiety could be removed by a single step of TFA cocktail treatment generally used
      for the final deprotection step in Fmoc-SPPS.

PMID- 26200328
TI  - Historical classics: editorial.

PMID- 26200327
TI  - Divergence and gene flow among Darwin's finches: A genome-wide view of adaptive
      radiation driven by interspecies allele sharing.
AB  - A recent analysis of the genomes of Darwin's finches revealed extensive
      interspecies allele sharing throughout the history of the radiation and
      identified a key locus responsible for morphological evolution in this group. The
      radiation of Darwin's finches on the Galapagos archipelago has long been regarded
      as an iconic study system for field ecology and evolutionary biology. Coupled
      with an extensive history of field work, these latest findings affirm the
      increasing acceptance of introgressive hybridization, or gene flow between
      species, as a significant contributor to adaptive evolution. Here, we review and
      discuss these findings in relation to both classical work on Darwin's finches and
      contemporary work showing similar evolutionary signatures in other biological
      systems. The continued unification of genomic data with field biology promises to
      further elucidate the molecular basis of adaptation in Darwin's finches and well
      beyond. 

PMID- 26200329
TI  - Botulinum toxin management of spasmodic dysphonia (laryngeal dystonia): a 12-year
      experience in more than 900 patients.

PMID- 26200330
TI  - The paralyzed larynx: an electromyographic study in dogs and humans. 1970.

PMID- 26200333
TI  - Utility of baseline impedance level measurement in patients with gastroesophageal
      reflux symptoms.
AB  - OBJECTIVE: Twenty-four-hour multichannel intraluminal impedance (MII) and pH
      monitoring is used for detecting reflux episodes in patients with
      gastroesophageal reflux (GER) disease. However, the clinical significance of
      baseline impedance levels (BILs) has not been well studied. We aimed to evaluate
      whether BILs are related to various reflux events or acid-related parameters and
      to determine whether BILs during specific intervals could be substituted for 24-h
      BILs. MATERIAL AND METHODS: One-hundred forty-two patients GER symptoms underwent
      24-h pH/impedance monitoring. We measured pH [(5 cm above the low esophageal
      sphincter (LES)] and BILs from three sites (3, 5, and 15 cm above the LES).
      RESULTS: Eighty-one subjects (57.0%) were diagnosed with gastroesophageal reflux
      disease, and 53 (37.3%) had acid reflux and 28 (19.7%) had nonacid reflux. The 24
      h BILs at distal sites were lower in the "reflux" group than in the "no reflux"
      group (p < 0.001) and lower in the "acid reflux" group than in the "nonacid
      reflux" group (p < 0.001). However, there was no significant difference in 24-h
      BILs at the proximal site among the "no reflux", "acid reflux", and "nonacid
      reflux" groups. The interclass correlation coefficient value of 24-h BILs with
      daytime 6-h BILs was 0.916 (95% CI 0.882-0.940) and that with nighttime 6-h BILs
      was 0.909 (95% CI 0.871-0.935). CONCLUSION: BILs are related to GER, especially
      acid reflux. Location and duration of assessment for BILs needs to be
      standardized. Six-hour BILs could be substitutes for 24-h BILs. During analysis
      of MII-pH, more attention should be paid to BILs in the lower esophagus.

PMID- 26200334
TI  - Sustainability: Bypassing the methane cycle.

PMID- 26200335
TI  - Metabolic co-dependence gives rise to collective oscillations within biofilms.
AB  - Cells that reside within a community can cooperate and also compete with each
      other for resources. It remains unclear how these opposing interactions are
      resolved at the population level. Here we investigate such an internal conflict
      within a microbial (Bacillus subtilis) biofilm community: cells in the biofilm
      periphery not only protect interior cells from external attack but also starve
      them through nutrient consumption. We discover that this conflict between
      protection and starvation is resolved through emergence of long-range metabolic
      co-dependence between peripheral and interior cells. As a result, biofilm growth
      halts periodically, increasing nutrient availability for the sheltered interior
      cells. We show that this collective oscillation in biofilm growth benefits the
      community in the event of a chemical attack. These findings indicate that
      oscillations support population-level conflict resolution by coordinating
      competing metabolic demands in space and time, suggesting new strategies to
      control biofilm growth. 

PMID- 26200336
TI  - Expression of barley SUSIBA2 transcription factor yields high-starch low-methane
      rice.
AB  - Atmospheric methane is the second most important greenhouse gas after carbon
      dioxide, and is responsible for about 20% of the global warming effect since pre
      industrial times. Rice paddies are the largest anthropogenic methane source and
      produce 7-17% of atmospheric methane. Warm waterlogged soil and exuded nutrients
      from rice roots provide ideal conditions for methanogenesis in paddies with
      annual methane emissions of 25-100-million tonnes. This scenario will be
      exacerbated by an expansion in rice cultivation needed to meet the escalating
      demand for food in the coming decades. There is an urgent need to establish
      sustainable technologies for increasing rice production while reducing methane
      fluxes from rice paddies. However, ongoing efforts for methane mitigation in rice
      paddies are mainly based on farming practices and measures that are difficult to
      implement. Despite proposed strategies to increase rice productivity and reduce
      methane emissions, no high-starch low-methane-emission rice has been developed.
      Here we show that the addition of a single transcription factor gene, barley
      SUSIBA2 (refs 7, 8), conferred a shift of carbon flux to SUSIBA2 rice, favouring
      the allocation of photosynthates to aboveground biomass over allocation to roots.
      The altered allocation resulted in an increased biomass and starch content in the
      seeds and stems, and suppressed methanogenesis, possibly through a reduction in
      root exudates. Three-year field trials in China demonstrated that the cultivation
      of SUSIBA2 rice was associated with a significant reduction in methane emissions
      and a decrease in rhizospheric methanogen levels. SUSIBA2 rice offers a
      sustainable means of providing increased starch content for food production while
      reducing greenhouse gas emissions from rice cultivation. Approaches to increase
      rice productivity and reduce methane emissions as seen in SUSIBA2 rice may be
      particularly beneficial in a future climate with rising temperatures resulting in
      increased methane emissions from paddies. 

PMID- 26200337
TI  - CDA directs metabolism of epigenetic nucleosides revealing a therapeutic window
      in cancer.
AB  - Cells require nucleotides to support DNA replication and repair damaged DNA. In
      addition to de novo synthesis, cells recycle nucleotides from the DNA of dying
      cells or from cellular material ingested through the diet. Salvaged nucleosides
      come with the complication that they can contain epigenetic modifications.
      Because epigenetic inheritance of DNA methylation mainly relies on copying of the
      modification pattern from parental strands, random incorporation of pre-modified
      bases during replication could have profound implications for epigenome fidelity
      and yield adverse cellular phenotypes. Although the salvage mechanism of 5-methyl
      2'deoxycytidine (5mdC) has been investigated before, it remains unknown how cells
      deal with the recently identified oxidized forms of 5mdC: 5-hydroxymethyl
      2'deoxycytidine (5hmdC), 5-formy-2'deoxycytidine (5fdC) and 5-carboxyl
      2'deoxycytidine (5cadC). Here we show that enzymes of the nucleotide salvage
      pathway display substrate selectivity, effectively protecting newly synthesized
      DNA from the incorporation of epigenetically modified forms of cytosine. Thus,
      cell lines and animals can tolerate high doses of these modified cytidines
      without any deleterious effects on physiology. Notably, by screening cancer cell
      lines for growth defects after exposure to 5hmdC, we unexpectedly identify a
      subset of cell lines in which 5hmdC or 5fdC administration leads to cell
      lethality. Using genomic approaches, we show that the susceptible cell lines
      overexpress cytidine deaminase (CDA). CDA converts 5hmdC and 5fdC into variants
      of uridine that are incorporated into DNA, resulting in accumulation of DNA
      damage, and ultimately, cell death. Our observations extend current knowledge of
      the nucleotide salvage pathway by revealing the metabolism of oxidized epigenetic
      bases, and suggest a new therapeutic option for cancers, such as pancreatic
      cancer, that have CDA overexpression and are resistant to treatment with other
      cytidine analogues. 

PMID- 26200338
TI  - Ophthalmology: Cataracts dissolved.

PMID- 26200340
TI  - Structure of the TRPA1 ion channel suggests regulatory mechanisms.

PMID- 26200339
TI  - Biogenesis and structure of a type VI secretion membrane core complex.
AB  - Bacteria share their ecological niches with other microbes. The bacterial type VI
      secretion system is one of the key players in microbial competition, as well as
      being an important virulence determinant during bacterial infections. It
      assembles a nano-crossbow-like structure in the cytoplasm of the attacker cell
      that propels an arrow made of a haemolysin co-regulated protein (Hcp) tube and a
      valine-glycine repeat protein G (VgrG) spike and punctures the prey's cell wall.
      The nano-crossbow is stably anchored to the cell envelope of the attacker by a
      membrane core complex. Here we show that this complex is assembled by the
      sequential addition of three type VI subunits (Tss)-TssJ, TssM and TssL-and
      present a structure of the fully assembled complex at 11.6 A resolution,
      determined by negative-stain electron microscopy. With overall C5 symmetry, this
      1.7-megadalton complex comprises a large base in the cytoplasm. It extends in the
      periplasm via ten arches to form a double-ring structure containing the carboxy
      terminal domain of TssM (TssMct) and TssJ that is anchored in the outer membrane.
      The crystal structure of the TssMct-TssJ complex coupled to whole-cell
      accessibility studies suggest that large conformational changes induce transient
      pore formation in the outer membrane, allowing passage of the attacking Hcp
      tube/VgrG spike. 

PMID- 26200341
TI  - Lanosterol reverses protein aggregation in cataracts.
AB  - The human lens is comprised largely of crystallin proteins assembled into a
      highly ordered, interactive macro-structure essential for lens transparency and
      refractive index. Any disruption of intra- or inter-protein interactions will
      alter this delicate structure, exposing hydrophobic surfaces, with consequent
      protein aggregation and cataract formation. Cataracts are the most common cause
      of blindness worldwide, affecting tens of millions of people, and currently the
      only treatment is surgical removal of cataractous lenses. The precise mechanisms
      by which lens proteins both prevent aggregation and maintain lens transparency
      are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens.
      It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a
      cholesterol synthesis pathway. Here we identify two distinct homozygous LSS
      missense mutations (W581R and G588S) in two families with extensive congenital
      cataracts. Both of these mutations affect highly conserved amino acid residues
      and impair key catalytic functions of LSS. Engineered expression of wild-type,
      but not mutant, LSS prevents intracellular protein aggregation of various
      cataract-causing mutant crystallins. Treatment by lanosterol, but not
      cholesterol, significantly decreased preformed protein aggregates both in vitro
      and in cell-transfection experiments. We further show that lanosterol treatment
      could reduce cataract severity and increase transparency in dissected rabbit
      cataractous lenses in vitro and cataract severity in vivo in dogs. Our study
      identifies lanosterol as a key molecule in the prevention of lens protein
      aggregation and points to a novel strategy for cataract prevention and treatment.

PMID- 26200342
TI  - Conversion of amides to esters by the nickel-catalysed activation of amide C-N
      bonds.
AB  - Amides are common functional groups that have been studied for more than a
      century. They are the key building blocks of proteins and are present in a broad
      range of other natural and synthetic compounds. Amides are known to be poor
      electrophiles, which is typically attributed to the resonance stability of the
      amide bond. Although amides can readily be cleaved by enzymes such as proteases,
      it is difficult to selectively break the carbon-nitrogen bond of an amide using
      synthetic chemistry. Here we demonstrate that amide carbon-nitrogen bonds can be
      activated and cleaved using nickel catalysts. We use this methodology to convert
      amides to esters, which is a challenging and underdeveloped transformation. The
      reaction methodology proceeds under exceptionally mild reaction conditions, and
      avoids the use of a large excess of an alcohol nucleophile. Density functional
      theory calculations provide insight into the thermodynamics and catalytic cycle
      of the amide-to-ester transformation. Our results provide a way to harness amide
      functional groups as synthetic building blocks and are expected to lead to the
      further use of amides in the construction of carbon-heteroatom or carbon-carbon
      bonds using non-precious-metal catalysis. 

PMID- 26200344
TI  - Molecular biology: Salvaging the genome.

PMID- 26200346
TI  - Structural biology: Arresting developments in receptor signalling.

PMID- 26200343
TI  - Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.
AB  - G-protein-coupled receptors (GPCRs) signal primarily through G proteins or
      arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects
      signalling to numerous G-protein-independent pathways. Here we report the crystal
      structure of a constitutively active form of human rhodopsin bound to a pre
      activated form of the mouse visual arrestin, determined by serial femtosecond X
      ray laser crystallography. Together with extensive biochemical and mutagenesis
      data, the structure reveals an overall architecture of the rhodopsin-arrestin
      assembly in which rhodopsin uses distinct structural elements, including
      transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin
      adopts the pre-activated conformation, with a ~20 degrees  rotation between the
      amino and carboxy domains, which opens up a cleft in arrestin to accommodate a
      short helix formed by the second intracellular loop of rhodopsin. This structure
      provides a basis for understanding GPCR-mediated arrestin-biased signalling and
      demonstrates the power of X-ray lasers for advancing the frontiers of structural
      biology. 

PMID- 26200345
TI  - Non-coding recurrent mutations in chronic lymphocytic leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic
      alterations determining the clinicobiological behaviour are not fully understood.
      Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL
      cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We
      extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3,
      ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding
      regions, including the 3' region of NOTCH1, which cause aberrant splicing events,
      increase NOTCH1 activity and result in a more aggressive disease. In addition,
      mutations in an enhancer located on chromosome 9p13 result in reduced expression
      of the B-cell-specific transcription factor PAX5. The accumulative number of
      driver alterations (0 to >=4) discriminated between patients with differences in
      clinical behaviour. This study provides an integrated portrait of the CLL genomic
      landscape, identifies new recurrent driver mutations of the disease, and suggests
      clinical interventions that may improve the management of this neoplasia. 

PMID- 26200347
TI  - Current Practices and Opportunities in a Resident Clinic Regarding the Care of
      Older Adults with Multimorbidity.
AB  - OBJECTIVES: Multimorbidity (>=2 chronic conditions) affects more than half of all
      older adults. The American Geriatrics Society developed and published guiding
      principles for the care of older adults with multimorbidity in 2012. Improved
      clinician training in caring for older adults with multimorbidity is needed, but
      it is not clear what opportunities arise within clinical encounters to apply the
      guiding principles or how clinicians at all stages of training currently practice
      in this area. This project aimed to characterize current practice and
      opportunities for improvement in an internal medicine residency clinic regarding
      the care of older adults with multimorbidity. DESIGN: Qualitative content
      analysis of audio-recorded clinic visits. SETTING AND PARTICIPANTS: Thirty clinic
      visits between 21 internal medicine residents and 30 of their primary care
      patients aged 65 and older with two or more chronic conditions were audio
      recorded. Patients' mean age was 73.6, and they had on average 3.7 chronic
      conditions and took 12.6 medications. MEASUREMENTS: Transcripts of the audio
      recorded visit discussions were analyzed using standard techniques of qualitative
      content analysis to describe the content and frequency of discussions in the
      clinic visits related to the five guiding principles: patient preferences,
      interpreting the evidence, prognosis, clinical feasibility, and optimizing
      therapies. RESULTS AND CONCLUSIONS: All visits except one included discussions
      that were thematically related to at least one guiding principle, suggesting
      regular opportunities to apply the guiding principles in primary care encounters
      with internal medicine residents. Discussions related to some guiding principles
      occurred much more frequently than others. Patients presented a number of
      opportunities to incorporate the guiding principles that the residents missed,
      suggesting target areas for future educational interventions.

PMID- 26200348
TI  - Development and Validation of Environmental DNA (eDNA) Markers for Detection of
      Freshwater Turtles.
AB  - Environmental DNA (eDNA) is a potentially powerful tool for detection and
      monitoring of rare species, including threatened native species and recently
      arrived invasive species. Here, we develop DNA primers for a suite of nine
      sympatric freshwater turtles, and use it to test whether turtle eDNA can be
      successfully detected in samples from aquaria and an outdoor pond. We also
      conduct a cost comparison between eDNA detection and detection through
      traditional survey methods, using data from field surveys at two sites in our
      target area. We find that eDNA from turtles can be detected using both
      conventional polymerase chain reaction (PCR) and quantitative PCR (qPCR), and
      that the cost of detection through traditional survey methods is 2-10X higher
      than eDNA detection for the species in our study range. We summarize necessary
      future steps for application of eDNA surveys to turtle monitoring and
      conservation and propose specific cases in which the application of eDNA could
      further the conservation of threatened turtle species. 

PMID- 26200349
TI  - Heavily Oiled Salt Marsh following the Deepwater Horizon Oil Spill, Ecological
      Comparisons of Shoreline Cleanup Treatments and Recovery.
AB  - The Deepwater Horizon oil spill affected hundreds of kilometers of coastal
      wetland shorelines, including salt marshes with persistent heavy oiling that
      required intensive shoreline "cleanup" treatment. Oiled marsh treatment involves
      a delicate balance among: removing oil, speeding the degradation of remaining
      oil, protecting wildlife, fostering habitat recovery, and not causing further
      ecological damage with treatment. To examine the effectiveness and ecological
      effects of treatment during the emergency response, oiling characteristics and
      ecological parameters were compared over two years among heavily oiled test plots
      subject to: manual treatment, mechanical treatment, natural recovery (no
      treatment, oiled control), as well as adjacent reference conditions. An
      additional experiment compared areas with and without vegetation planting
      following treatment. Negative effects of persistent heavy oiling on marsh
      vegetation, intertidal invertebrates, and shoreline erosion were observed. In
      areas without treatment, oiling conditions and negative effects for most marsh
      parameters did not considerably improve over two years. Both manual and
      mechanical treatment were effective at improving oiling conditions and vegetation
      characteristics, beginning the recovery process, though recovery was not complete
      by two years. Mechanical treatment had additional negative effects of mixing oil
      into the marsh soils and further accelerating erosion. Manual treatment appeared
      to strike the right balance between improving oiling and habitat conditions while
      not causing additional detrimental effects. However, even with these
      improvements, marsh periwinkle snails showed minimal signs of recovery through
      two years, suggesting that some ecosystem components may lag vegetation recovery.
      Planting following treatment quickened vegetation recovery and reduced shoreline
      erosion. Faced with comparable marsh oiling in the future, we would recommend
      manual treatment followed by planting. We caution against the use of intensive
      treatment methods with lesser marsh oiling. Oiled controls (no treatment "set
      asides") are essential for judging marsh treatment effectiveness and ecological
      effects; we recommend their use when applying intensive treatment methods. 

PMID- 26200350
TI  - Origin of Hofmeister Effects for Complex Systems.
AB  - Hofmeister effects have been recognized as important as Mendel's work was to
      genetics while remain largely controversial, especially for the mechanistic
      aspects. Here we demonstrated that complex colloids in electrolyte solutions show
      resembling aggregation kinetics as model colloid, and then quantitatively
      evaluated the resulting Hofmeister effects. Mechanism for the aggregation of
      complex colloids has been proposed that is closely associated with the charges of
      their constituents; despite that, electrostatic interactions play a minor role
      while polarization effect is evidenced to be the driving force for the
      aggregation processes. Polarization effect is further ascribed to arouse the
      resulting Hofmeister effects, which is supported by the fine correlation of
      activation energies vs. polarizability data of different alkali ions and the
      calculations of dipole moments for minerals with different charges and adsorbed
      alkali ions. Because of neglecting polarization effect, the prevailing DLVO
      theory is not sufficient to describe Hofmeister effects that are ubiquitous in
      nature. We speculate that polarization effect should also be responsible for
      Hofmeister effects of other charged systems such as proteins and membranes. 

PMID- 26200351
TI  - Large-Scale Habitat Corridors for Biodiversity Conservation: A Forest Corridor in
      Madagascar.
AB  - In biodiversity conservation, habitat corridors are assumed to increase landscape
      level connectivity and to enhance the viability of otherwise isolated
      populations. While the role of corridors is supported by empirical evidence,
      studies have typically been conducted at small spatial scales. Here, we assess
      the quality and the functionality of a large 95-km long forest corridor
      connecting two large national parks (416 and 311 km2) in the southeastern
      escarpment of Madagascar. We analyze the occurrence of 300 species in 5 taxonomic
      groups in the parks and in the corridor, and combine high-resolution forest cover
      data with a simulation model to examine various scenarios of corridor
      destruction. At present, the corridor contains essentially the same communities
      as the national parks, reflecting its breadth which on average matches that of
      the parks. In the simulation model, we consider three types of dispersers:
      passive dispersers, which settle randomly around the source population; active
      dispersers, which settle only in favorable habitat; and gap-avoiding active
      dispersers, which avoid dispersing across non-habitat. Our results suggest that
      long-distance passive dispersers are most sensitive to ongoing degradation of the
      corridor, because increasing numbers of propagules are lost outside the forest
      habitat. For a wide range of dispersal parameters, the national parks are large
      enough to sustain stable populations until the corridor becomes severely broken,
      which will happen around 2065 if the current rate of forest loss continues. A
      significant decrease in gene flow along the corridor is expected after 2040, and
      this will exacerbate the adverse consequences of isolation. Our results
      demonstrate that simulation studies assessing the role of habitat corridors
      should pay close attention to the mode of dispersal and the effects of regional
      stochasticity. 

PMID- 26200352
TI  - The Glycogen Synthase Kinase 3alpha and beta Isoforms Differentially Regulates
      Interleukin-12p40 Expression in Endothelial Cells Stimulated with Peptidoglycan
      from Staphylococcus aureus.
AB  - Glycogen synthase kinase 3 (GSK3) is a constitutively active regulatory enzyme
      that is important in cancer, diabetes, and cardiovascular, neurodegenerative, and
      psychiatric diseases. While GSK3alpha is usually important in neurodegenerative
      and psychiatric diseases GSK3beta is fundamental in the inflammatory response
      caused by bacterial components. Peptidoglycan (PGN), one of the most abundant
      cell-wall structures of Gram-positive bacteria, is an important inducer of
      inflammation. To evaluate whether inhibition of GSK3alpha and GSK3beta activity
      in bovine endothelial cells (BEC) regulates the expression of the pro
      inflammatory cytokine IL-12p40, we treated BEC with SDS-purified PGN from
      Staphylococcus aureus. We found that PGN triggered a TLR2/PI3K/Akt-dependent
      phosphorylation of GSK3alpha at Ser21, GSK3beta at Ser9, and NF-kappaB p65
      subunit (p65) at Ser536, and the phosphorylation of GSK3alpha was consistently
      higher than that of GSK3beta. The expression of IL-12p40 was inhibited in BEC
      stimulated with PGN and pre-treated with a specific neutralizing anti-TLR2
      antibody that targets the extracellular domain of TLR2 or by the addition of Akt
      i IV (an Akt inhibitor). Inhibition of GSK3alpha and GSK3beta with LiCl or
      SB216763 induced an increase in IL-12p40 mRNA and protein. The effect of each
      isoform on IL-12p40 expression was evaluated by siRNA-gene expression silencing
      of GSK3alpha and GSK3beta. GSK3alpha gene silencing resulted in a marked increase
      in IL-12p40 mRNA and protein while GSK3beta gene silencing had the opposite
      effect on IL-12p40 expression. These results indicate that the TLR2/PI3K/Akt
      dependent inhibition of GSK3alpha activity also plays an important role in the
      inflammatory response caused by stimulation of BEC with PGN from S. aureus. 

PMID- 26200353
TI  - Aligning Natural Resource Conservation and Flood Hazard Mitigation in California.
AB  - Flooding is the most common and damaging of all natural disasters in the United
      States, and was a factor in almost all declared disasters in U.S. HISTORY: Direct
      flood losses in the U.S. in 2011 totaled $8.41 billion and flood damage has also
      been on the rise globally over the past century. The National Flood Insurance
      Program paid out more than $38 billion in claims since its inception in 1968,
      more than a third of which has gone to the one percent of policies that
      experienced multiple losses and are classified as "repetitive loss." During the
      same period, the loss of coastal wetlands and other natural habitat has
      continued, and funds for conservation and restoration of these habitats are very
      limited. This study demonstrates that flood losses could be mitigated through
      action that meets both flood risk reduction and conservation objectives. We found
      that there are at least 11,243km2 of land in coastal California, which is both
      flood-prone and has natural resource conservation value, and where a
      property/structure buyout and habitat restoration project could meet multiple
      objectives. For example, our results show that in Sonoma County, the extent of
      land that meets these criteria is 564km2. Further, we explore flood mitigation
      grant programs that can be a significant source of funds to such projects. We
      demonstrate that government funded buyouts followed by restoration of targeted
      lands can support social, environmental, and economic objectives: reduction of
      flood exposure, restoration of natural resources, and efficient use of limited
      governmental funds.

PMID- 26200354
TI  - Evaluating Temporal Consistency in Marine Biodiversity Hotspots.
AB  - With the ongoing crisis of biodiversity loss and limited resources for
      conservation, the concept of biodiversity hotspots has been useful in determining
      conservation priority areas. However, there has been limited research into how
      temporal variability in biodiversity may influence conservation area
      prioritization. To address this information gap, we present an approach to
      evaluate the temporal consistency of biodiversity hotspots in large marine
      ecosystems. Using a large scale, public monitoring dataset collected over an
      eight year period off the US Pacific Coast, we developed a methodological
      approach for avoiding biases associated with hotspot delineation. We aggregated
      benthic fish species data from research trawls and calculated mean hotspot
      thresholds for fish species richness and Shannon's diversity indices over the
      eight year dataset. We used a spatial frequency distribution method to assign
      hotspot designations to the grid cells annually. We found no areas containing
      consistently high biodiversity through the entire study period based on the mean
      thresholds, and no grid cell was designated as a hotspot for greater than 50% of
      the time-series. To test if our approach was sensitive to sampling effort and the
      geographic extent of the survey, we followed a similar routine for the northern
      region of the survey area. Our finding of low consistency in benthic fish
      biodiversity hotspots over time was upheld, regardless of biodiversity metric
      used, whether thresholds were calculated per year or across all years, or the
      spatial extent for which we calculated thresholds and identified hotspots. Our
      results suggest that static measures of benthic fish biodiversity off the US West
      Coast are insufficient for identification of hotspots and that long-term data are
      required to appropriately identify patterns of high temporal variability in
      biodiversity for these highly mobile taxa. Given that ecological communities are
      responding to a changing climate and other environmental perturbations, our work
      highlights the need for scientists and conservation managers to consider both
      spatial and temporal dynamics when designating biodiversity hotspots. 

PMID- 26200355
TI  - Rethinking Rice Preparation for Highly Efficient Removal of Inorganic Arsenic
      Using Percolating Cooking Water.
AB  - A novel way of cooking rice to maximize the removal of the carcinogen inorganic
      arsenic (Asi) is presented here. In conventional rice cooking water and grain are
      in continuous contact, and it is known that the larger the water:rice cooking
      ratio, the more Asi removed by cooking, suggesting that the Asi in the grain is
      mobile in water. Experiments were designed where rice is cooked in a continual
      stream of percolating near boiling water, either low in Asi, or Asi free. This
      has the advantage of not only exposing grain to large volumes of cooking water,
      but also physically removes any Asi leached from the grain into the water
      receiving vessel. The relationship between cooking water volume and Asi removal
      in conventional rice cooking was demonstrated for the rice types under study. At
      a water-to-rice cooking ratio of 12:1, 57+/-5% of Asi could be removed, average
      of 6 wholegrain and 6 polished rice samples. Two types of percolating technology
      were tested, one where the cooking water was recycled through condensing boiling
      water steam and passing the freshly distilled hot water through the grain in a
      laboratory setting, and one where tap water was used to cook the rice held in an
      off-the-shelf coffee percolator in a domestic setting. Both approaches proved
      highly effective in removing Asi from the cooking rice, with up to 85% of Asi
      removed from individual rice types. For the recycled water experiment 59+/-8% and
      69+/-10% of Asi was removed, on average, compared to uncooked rice for polished
      (n=27) and wholegrain (n=13) rice, respectively. For coffee percolation there was
      no difference between wholegrain and polished rice, and the effectiveness of Asi
      removal was 49+/-7% across 6 wholegrain and 6 polished rice samples. The
      manuscript explores the potential applications and further optimization of this
      percolating cooking water, high Asi removal, discovery. 

PMID- 26200356
TI  - Overproduction of a Model Sec- and Tat-Dependent Secretory Protein Elicits
      Different Cellular Responses in Streptomyces lividans.
AB  - Streptomyces lividans is considered an efficient host for the secretory
      production of homologous and heterologous proteins. To identify possible
      bottlenecks in the protein production process, a comparative transcriptomic
      approach was adopted to study cellular responses during the overproduction of a
      Sec-dependent model protein (alpha-amylase) and a Tat-dependent model protein
      (agarase) in Streptomyces lividans. The overproduction of the model secretory
      proteins via the Sec or the Tat route in S. lividans does elicit a different
      major cell response in the bacterium. The stringent response is a bacterial
      response to nutrients' depletion, which naturally occurs at late times of the
      bacterial cell growth. While the induction of the stringent response at the
      exponential phase of growth may limit overall productivity in the case of the Tat
      route, the induction of that response does not take place in the case of the Sec
      route, which comparatively is an advantage in secretory protein production
      processes. Hence, this study identifies a potential major drawback in the
      secretory protein production process depending on the secretory route, and
      provides clues to improving S. lividans as a protein production host. 

PMID- 26200357
TI  - Measuring Social Relationships in Different Social Systems: The Construction and
      Validation of the Evaluation of Social Systems (EVOS) Scale.
AB  - Social interactions have gained increasing importance, both as an outcome and as
      a possible mediator in psychotherapy research. Still, there is a lack of adequate
      measures capturing relational aspects in multi-person settings. We present a new
      measure to assess relevant dimensions of quality of relationships and collective
      efficacy regarding interpersonal interactions in diverse personal and
      professional social systems including couple partnerships, families, and working
      teams: the EVOS. Theoretical dimensions were derived from theories of systemic
      family therapy and organizational psychology. The study was divided in three
      parts: In Study 1 (N = 537), a short 9-item scale with two interrelated factors
      was constructed on the basis of exploratory factor analysis. Quality of
      relationship and collective efficacy emerged as the most relevant dimensions for
      the quality of social systems. Study 2 (N = 558) confirmed the measurement model
      using confirmatory factor analysis and established validity with measures of
      family functioning, life satisfaction, and working team efficacy. Measurement
      invariance was assessed to ensure that EVOS captures the same latent construct in
      all social contexts. In Study 3 (N = 317), an English language adaptation was
      developed, which again confirmed the original measurement model. The EVOS is a
      theory-based, economic, reliable, and valid measure that covers important aspects
      of social relationships, applicable for different social systems. It is the first
      instrument of its kind and an important addition to existing measures of social
      relationships and related outcome measures in therapeutic and other counseling
      settings involving multiple persons. 

PMID- 26200358
TI  - Atrial fibrillation and NPPA gene p.S64R mutation: are cardiologists helpless
      spectators of healthy mutation carriers?
AB  - AIMS: Heterozygous p.(Ser64Arg) mutation in the natriuretic peptide precursor A
      gene has been associated with atrial fibrillation in the presence of common
      single nucleotide polymorphisms (rs10033464 and rs2200733; 4q25) that would act
      as modifiers. METHODS: We screened natriuretic peptide precursor A gene in 583
      individuals and identified three unrelated carriers of the p.(Ser64Arg) mutation
      (0.5%). RESULTS: Only one of the three mutation carriers had episodes of atrial
      fibrillation. Cascade screening of the three families identified seven additional
      mutation carriers, none showing atrial fibrillation. The patients with atrial
      fibrillation also carried the rs2200733, which was however found in four
      additional nonatrial fibrillation family members and carriers of the
      p.(Ser64Arg). The prevalence of atrial fibrillation in p.(Ser64Arg) carriers was
      10% and in those combining the mutation with the risk single nucleotide
      polymorphisms was 20%. In the unique mutated patient with atrial fibrillation,
      the arrhythmias was refractory to both pharmacological and ablation treatment,
      during 16 years of follow-up; his electrophysiological phenotype was
      characterized by short atrial cycle lengths with a median value of 131 ms that
      suggests shortening of atrial action potential. CONCLUSION: The prevalence of
      p.(Ser64Arg) mutation is low in the general population as is the prevalence of
      atrial fibrillation in mutation carriers (1/10). Atrial fibrillation in the
      affected mutated patient was lone at onset and progressively evolved with
      peculiar electrophysiological patterns.

PMID- 26200359
TI  - Comparison of two passive warming devices for prevention of perioperative
      hypothermia in dogs.
AB  - OBJECTIVE: To compare effects of two passive warming methods combined with a
      resistive heating mat on perioperative hypothermia in dogs. MATERIALS AND
      METHODS: Fifty-two dogs were enrolled and randomly allocated to receive a
      reflective blanket (Blizzard Blanket) or a fabric blanket (VetBed). In addition,
      in the operating room all dogs were placed onto a table with a resistive heating
      mat covered with a fabric blanket. Rectal temperature measurements were taken at
      defined points. Statistical analysis was performed comparing all Blizzard Blanket
      treated to all VetBed-treated dogs, and VetBed versus Blizzard Blanket dogs
      within spay and castrate groups, spay versus castrate groups and within groups
      less than 10 kg or more than 10 kg bodyweight. RESULTS: Data from 39 dogs were
      used for analysis. All dogs showed a reduction in perioperative rectal
      temperature. There were no detected statistical differences between treatments or
      between the different groups. CLINICAL SIGNIFICANCE: This study supports previous
      data on prevalence of hypothermia during surgery. The combination of active and
      passive warming methods used in this study prevented the development of severe
      hypothermia, but there were no differences between treatment groups.

PMID- 26200360
TI  - Is income inequality decreasing in Brazil?

PMID- 26200361
TI  - Tuberculosis in Brazilian prisons: responsibility of the state and double
      punishment for the inmates.

PMID- 26200362
TI  - ["No" for stacked young bodybuilders, "yes" for manthers: the biomedical
      discourse on anabolic steroids and health].
AB  - The article addresses the use of anabolic androgenic steroids (AAS), synthetic
      drugs whose abuse has been characterized as a public health problem, operated in
      the opposition between "medical" and "non-medical" uses. A qualitative approach
      was used to analyze the text in 76 biomedical articles published from 2002 to
      2012. The discourse shows a persistent ban on non-medically regulated use of AAS
      by young people, while the limits on clinically qualified use appear to expand
      among older people, even given the contradictions straining the argument on the
      prevention of health risks. Moralizing biopolitical stances appear, based on
      gender distinctions or under the aegis of criminalizing drug use. 

PMID- 26200363
TI  - Low back pain prevalence in Brazil: a systematic review.
AB  - The article describes the methodological quality of published studies on
      prevalence of low back pain in Brazil. Eighteen studies were considered eligible
      after searches in the following electronic databases: LILACS, PubMed, Embase,
      CINAHL, SPORTDiscus and SciELO. A high source of bias was observed in the
      criteria for external validity related to sampling, in addition to non-response
      bias. Considering the criteria for internal validity, the main sources of bias
      were the lack of an acceptable definition of low back pain and the use of
      instruments that lacked proven reliability and validity. No representative study
      was found that provides a generalizable prevalence of low back pain in Brazil.
      The published studies included in this review showed a high risk of bias that
      affects the prevalence data. Future studies with appropriate methodological
      design are necessary to verify the real impact of low back pain in Brazil and
      allow comparisons. 

PMID- 26200364
TI  - [Evaluation of eight Clinical Protocols and Therapeutic Guidelines under the
      Brazilian Ministry of Health using the AGREE II instrument: a pilot study].
AB  - The number of clinical guidelines is increasing worldwide, while there are
      concerns regarding their quality. In 2000, the Brazilian Ministry of Health began
      its process of creating clinical guidelines, called Clinical Protocols and
      Therapeutic Guidelines (PCDT). The goal of this study was to assess the quality
      of Brazilian guidelines approved since 2009 using the AGREE II instrument
      (Appraisal of Guidelines for Research and Evaluation). We identified 59 PCDT from
      2009 to 2012, of which eight were randomly selected and evaluated by three
      independent evaluators. For the item "recommends the guidelines", two evaluators
      recommended the use of all eight, but with modifications, and one did not
      recommend any to the guidelines. Regarding the item "global quality of the
      guidelines" (varying from 1 to 7), the mean was 4.25 (SD = 0.46). The results
      showed the need for adjustments in the PCDT in relation to AGREE II domains.
      However, due to the instrument's limitations, further studies are needed,
      including the quality of evidence used in the PCDT. 

PMID- 26200365
TI  - [Regionalization and human development: a typology of health regions in Brazil].
AB  - This article aimed to present a proposal for characterizing health regions in
      Brazil based on human development, contributing to the identification of
      comparable geographic areas for observation, analysis, and monitoring of
      performance in regionalized health systems. The dimensions of the Municipal Human
      Development Index were calculated for the health regions by aggregating data from
      municipalities, weighted by population size. The grouping of health regions in 5
      groups, based on combinations of life expectancy, income, and schooling, was
      determined by the K-Means method. Approximately half of Brazil's health regions
      were classified as type 1 and the other half as types 3 to 5. The typology
      provides a clustering model for homogeneous health regions, consistent with the
      theoretical assumptions of PROADESS. The choice of well-established indicators
      and aggregation methods tends to facilitate their comprehension and use by the
      actors involved in the administration of the Brazilian Unified National Health
      System (SUS). 

PMID- 26200366
TI  - [Equity in coverage by the Family Health Strategy in Minas Gerais State, Brazil].
AB  - The Family Health Strategy (FHS) plays an important role in prevention and in
      monitoring families in the Brazilian Unified National Health System. This study
      aims to analyze equity in the coverage of these services in the urban areas of
      Minas Gerais State, Brazil. The research is unprecedented and analyzes several
      markers for four target groups: women, pregnant women, children, and the elderly.
      The study is representative of the various health macro-regions. In 2012, 6,797
      households were surveyed, with 5,820 women, 1,758 children, and 3,629 elderly. To
      analyze equity, FHS coverage rates were calculated according to family income,
      and concentration indices and curves were estimated. The results show that the
      FHS is an equitable policy. The indicators show that poorer households have
      higher visitation rates under the FHS. Coverage of the eligible population is
      quite high: 88% of households received at least one visit from FHS professionals
      in the previous 12 months, resulting in a concentration index near zero. 

PMID- 26200367
TI  - Factors associated with non-adherence to antiretroviral therapy in adults with
      AIDS in the first six months of treatment in Salvador, Bahia State, Brazil.
AB  - The control of viral replication is essential in the highly active antiretroviral
      therapy (HAART), and adherence to therapy is instrumental for such control.
      Individual and external factors influence adhesion to the use of antiretroviral
      (ARV) drugs. This is a cross-sectional study to investigate factors associated
      with non-adherence to HAART in AIDS patients in Salvador, Bahia State, Brazil,
      with age >= 13 years and first prescription in 2009. Data was collected from
      patient charts and pharmacy records. From a total of 216 patients, 65.3% were
      males; mean age 37.8 +/- 9.5 years; single, 67.9%; heterosexual, 64%; more than 8
      years of school education, 65.3%; alcohol users, 61.5%; non-smokers, 75,1% or non
      illicit drug users, 93.7%. A proportion of 94% started ARV therapy with TCD4+ <
      350 cells/mm3; 61.8% were symptomatic; and 68.4% had an adverse drug reaction.
      The prevalence of non-adherence was 25%. The variables associated were: longer
      time between HIV infection and AIDS (aOR = 3.9), adverse drug reaction (aOR =
      2.4), under 34 years of age (aOR = 2.2), less than 8 years of school education
      (aOR = 2.2) and illicit drugs use (aOR = 2.6). A high-non-adherence rate is an
      important problem within the first six months of HAART. 

PMID- 26200368
TI  - [Factors associated with work-related accidents in the informal commercial
      sector].
AB  - This study aimed to estimate the incidence of non-fatal work-related accidents in
      the informal commercial sector and analyze associated socio-demographic,
      occupational, workplace, and health factors, in a cross-sectional survey of 434
      workers in the business district of Jequie, Bahia State, Brazil, in 2013.
      Logistic regression was used to assess factors associated with accidents.
      Incidence of accidents in the previous 12 months was estimated at 32.3%, and
      multivariate analysis showed higher odds of accidents in male sex workers (OR =
      1.61), young individuals (OR = 4.62), meat or poultry workers (OR = 9.55), and
      workers performing heavy physical work (OR = 1.71). The results show the need for
      public policies to prevent accidents in the informal commercial sector. 

PMID- 26200369
TI  - [Domains of physical activity in slave-descendant communities in Southwest Bahia
      State, Brazil: a population-based study].
AB  - This study aimed to describe the prevalence of physical activity (PA) and
      associated factors in various domains (leisure-time, work, home, and commuting)
      among quilombolas (descendants of African slaves) in Bahia State, Brazil. This
      was a cross-sectional study of 797 individuals from 18 to 100 years of age. The
      study adopted a cutoff point of 150 minutes of PA per week. A hierarchical
      Poisson model was used. The highest prevalence of PA was at work (42.1%),
      followed by the home environment (39.3%), commuting (35.5%), and leisure time
      (13.1%). PA at work was associated with male gender, lower age, higher schooling,
      and consumption of alcohol and fruits. PA in the household domain was associated
      with female gender, lower age, marital status (married), and negative self-rated
      health. In commuting, PA was associated with male gender and lower age bracket,
      and during leisure time with safety, male gender, lower age, and higher
      schooling. The study concludes that this slave-descendant community displays a
      profile of PA that is characteristic of rural groups (more active at work, with
      little leisure-time activity). The determinants of PA were similar to those seen
      in urban groups. 

PMID- 26200370
TI  - [Poor dad, poor child? An investigation of intergenerational income mobility in
      the 1982 Birth Cohort in Pelotas, Rio Grande do Sul State, Brazil].
AB  - Brazil is one of the countries with the lowest intergenerational income mobility.
      This article aimed to analyze intergenerational income mobility in the 1982 Birth
      Cohort in Pelotas, Rio Grande do Sul State. Two methods were used,
      intergenerational income elasticity and quantile regressions, in order to measure
      heterogeneity in income mobility as a function of different levels of parents'
      past income. The results show relatively high income mobility for Brazilian
      standards. The main explanation is that the data cover the children's income at a
      younger age (about 23 years). Quantile regressions show higher social mobility in
      the intermediary social stratum. The results reinforce the notion of two opposite
      "traps", poverty and wealth. 

PMID- 26200371
TI  - [A sociography of elderly victims of family violence in Portugal].
AB  - This article presents data on violence against persons aged 60 years or older and
      living in Portugal for at least 12 months. The cross-sectional descriptive study
      collected data with a face-to-face questionnaire applied to victims that had
      sought assistance at three government institutions and one non-governmental
      support service for victims. The non-probabilistic sample included 510 victims of
      violence in family settings. Physical and psychological violence were the most
      common (87.8% and 69.6%, respectively). Financial violence was reported by 47.5%
      of the victims, followed by sexual assault (7.5%) and neglect (6.5%). The
      majority of victims (74.1%) reported more than one type of violence. Victims were
      mostly women, and mean age was 70.7 years. Most of the perpetrators belonged to
      the nuclear family, namely spouses or partners, sons/sons-in-law, and
      daughters/daughters-in-law. However, differences were observed according to
      victim's gender. The results indicate that violence is not a uniform phenomenon,
      presenting different configurations. 

PMID- 26200372
TI  - 2010 A(H1N1) vaccination in pregnant women in Brazil: identifying coverage and
      associated factors.
AB  - We studied vaccination coverage and its associated factors in the 2010 pandemic
      influenza vaccination of Brazilian pregnant women. A cross-sectional study of
      pregnant women who had given birth was performed in a municipality in southern
      Brazil, in 2010. Data about vaccination against A(H1N1) and sociodemographic
      characteristics, morbidities and prenatal care were collected. Statistical
      analysis was performed using a Poisson regression. Coverage was 77.4%. Most were
      vaccinated in the public sector (97.6%) and in the second trimester (47%).
      Associated factors that increased vaccination were marriage, older age, first
      income quartile, prenatal care and influenza before pregnancy. Education and skin
      color were not significantly associated with vaccination. The vaccination
      campaign was extensive and exhibited no inequality. Prenatal care was the factor
      that most affected vaccination coverage, reflecting its importance for
      vaccination campaign success. 

PMID- 26200373
TI  - [Risk of contamination from exposure to Rio Doce water: a case study on the
      population's perceptions in Tumiritinga, Minas Gerais State, Brazil].
AB  - The close relationship between local residents and the Rio Doce and the river's
      recurrent flooding lead to continuous exposure of the population to waterborne
      diseases. Given the epidemiological importance of such diseases in the region,
      this study analyzes the association between risk perception of contamination and
      river water use, as well as the heuristic mechanisms used by individuals to shape
      their personal perception of risk. Regression models coupled with thematic
      network analysis were applied to primary data from 352 households in 2012. The
      data are representative of urban residents of Tumiritinga, Minas Gerais State,
      Brazil. The results show that while 92.6% of respondents perceived high risk of
      waterborne diseases, only 11.4% reported not making direct use of the river. This
      apparent paradox is explained by the lack of information on transmission
      mechanisms, underestimating the perception of contamination. Public campaigns to
      promote preventive behavior should stress how waterborne diseases are
      transmitted, using simple examples to reach a wider local audience. 

PMID- 26200374
TI  - [Determinants of the time between breast cancer diagnosis and initiation of
      treatment in Brazilian women].
AB  - This study aimed to analyze the time elapsed between breast cancer diagnosis and
      initiation of treatment in woman treated from 2000 to 2011 in the Brazilian
      public health system and to identify factors associated with delayed onset of
      treatment. This retrospective cohort study included 137,593 women diagnosed in
      239 hospitals in Brazil from 2000 to 2011. In 63.1% of cases the time between
      diagnosis and treatment was 60 days. Delayed treatment was associated with
      nonwhite skin color (OR = 1.18; 95%CI: 1.13-1.23), single marital status (OR =
      1.05; 95%CI: 1.01-1.09), less than eight years of schooling (OR = 1.13; 95%CI:
      1.08-1.18), early-stage disease (OR = 1.27; 95%CI: 1.22-1.32), treatment from
      2006 to 2011 (OR = 1.54; 95%CI: 1.47-1.60), and patients in the public health
      system (OR = 1.19; 95%CI: 1.13-1.25). Stratified analysis showed variability of
      factors between regions of Brazil. The identification of factors associated with
      delayed initiation of breast cancer treatment can support the development of
      interventions targeted to specific population groups. 

PMID- 26200375
TI  - The burden of smoking-related diseases in Brazil: mortality, morbidity and costs.
AB  - Advances in tobacco control in Brazil can be reflected in the decrease in
      prevalence over the past two decades. Death statistics and the occurrence of
      events and direct costs attributable to tobacco-related diseases have not been
      frequently estimated in the country. The goal of this article is to estimate the
      burden of smoking in 2011 regarding mortality, morbidity and medical care costs
      of the main tobacco-related diseases. A probabilistic microsimulation health
      economic model was built. The model incorporates the natural history, costs and
      quality of life of all the tobacco-related adult-specific diseases. Smoking was
      accountable for 147,072 deaths, 2.69 million years of life lost, 157,126 acute
      myocardial infarctions, 75,663 strokes, and 63,753 cancer diagnoses. The direct
      cost for the health system was of BRL 23.37 billion. The monitoring of tobacco
      related burden is an important strategy to guide decision-makers and to
      strenghten health public policies. 

PMID- 26200376
TI  - Family structure and use of prenatal care.
AB  - This cross-sectional study intended to assess the use of prenatal care according
      to the family structure in a population with free universal access to prenatal
      care. In 2005-2006, the Portuguese birth cohort was assembled by the recruitment
      of puerperae at public maternity wards in Porto, Portugal. In the current
      analysis, 7,211 were included. Data on socio-demographic characteristics,
      obstetric history, and prenatal care were self-reported. Single mothers were
      considered as those whose household composition did not include a partner at
      delivery. Approximately 6% of the puerperae were single mothers. These women were
      more likely to have an unplanned pregnancy (OR = 6.30; 95%CI: 4.94-8.04), an
      inadequate prenatal care (OR = 2.30; 95%CI: 1.32-4.02), and to miss the
      ultrasound and the intake of folic acid supplements during the first trimester of
      pregnancy (OR = 1.71; 95%CI: 1.30-2.27; and OR = 1.67; 95%CI: 1.32-2.13,
      respectively). The adequacy and use of prenatal care was less frequent in single
      mothers. Educational interventions should reinforce the use and early initiation
      of prenatal care. 

PMID- 26200377
TI  - [Does the GHQ-12 scoring system affect its factor structure? An exploratory study
      of Ibero American students].
AB  - This study aimed to evaluate whether the scoring system of the General Health
      Questionnaire (GHQ-12) alters the instrument's factor structure. The method
      considered 1,972 university students from nine Ibero American countries. Modeling
      was performed with structural equations for 1, 2, and 3 latent factors. The
      mechanism for scoring the questions was analyzed within each type of structure.
      The results indicate that models with 2 and 3 factors show better goodness-of
      fit. In relation to scoring mechanisms, procedure 0-1-1-1 for models with 2 and 3
      factors showed the best fit. In conclusion, there appears to be a relationship
      between the response format and the number of factors identified in the
      instrument's structure. The model with the best fit was 3-factor 0-1-1-1
      formatted, but 0-1-2-3 has acceptable and more stable indicators and provides a
      better format for two- and three-dimensional models. 

PMID- 26200378
TI  - Association of handgrip strength with self-reported diseases in adults in Rio
      Branco, Acre State, Brazil: a population-based study.
AB  - This study aimed to analyze the association of handgrip strength with self
      reported diseases and multimorbidity among adults in Rio Branco, Acre State,
      Brazil, through a population based survey involving 1,395 adults of both sexes.
      Associations by sex were estimated by logistic regression analysis. The mean
      handgrip strength in men (44.8kg) is higher than in women (29kg) and decrease
      with age. The mean handgrip strength difference between those classified as
      strong and weak was 21kg and 15.5kg for men and woman, respectively. Controlling
      for age group, body mass index and physical activity when it was relevant, men
      with low handgrip strength were more likely to have hypertension [OR = 2.21
      91.35; 3.61)], diabetes [OR = 4.18 (1.35; 12.95)], musculoskeletal disorders [OR
      = 1.67 (1.07; 2.61)] and multimorbidity [OR = 1.99 (1.27; 3.12)]. Among woman,
      associations between handgrip strength and cardiovascular disease, dyslipidemia,
      musculoskeletal disorders and multimorbidity were not sustained in the
      multivariate models. This study endorses the use of handgrip strength as a health
      biomarker. 

PMID- 26200379
TI  - HIV-1 incidence among people seeking voluntary counseling and testing centers,
      including pregnant women, in Pernambuco State, Northeast Brazil.
AB  - The HIV-1 epidemic in Brazil has displayed new characteristics over time, with an
      increase in heterosexual transmission and a decline in the male-to-female ratio
      in AIDS cases. HIV screening was offered to patients attending the Voluntary
      Counseling and Testing Center in Paulista, Greater Metropolitan Recife,
      Pernambuco State, in Northeast Brazil, to determine HIV-1 incidence. BED capture
      enzyme immunoassay (BED-CEIA) was used to measure HIV-1 incidence, comparing it
      to the AxSYM avidity index method (Ax-AI). From 2006 to 2009, 14,014 individuals
      were tested, and only 18 pregnant women were diagnosed with HIV infection,
      resulting in 0.15% annual incidence (95%CI: 0-0.33), significantly lower than in
      men (1.03; 95%CI: 0.45-1.61) and non-pregnant women (0.50; 95%CI: 0.11-0.89).
      Despite the low HIV-1 incidence in pregnant women, the high rate of recent
      infection detected during prenatal care emphasizes the need to increase measures
      to prevent vertical transmission. 

PMID- 26200380
TI  - [Universal health coverage].

PMID- 26200381
TI  - Google Trends (GT) related to influenza.

PMID- 26200384
TI  - BILATERAL LAMELLAR MACULAR HOLE SURGERY IN RETINITIS PIGMENTOSA.
AB  - PURPOSE: To report the visual and anatomical outcomes after surgical repair of
      bilateral lamellar macular holes in a patient with retinitis pigmentosa. METHODS:
      A 66-year-old woman with a 39-year history of retinitis pigmentosa presented with
      decreased visual acuity in both eyes. On examination, she was diagnosed with
      lamellar macular holes in both eyes. She underwent pars plana vitrectomy with
      internal limiting membrane peeling and short-term gas tamponade in both eyes.
      RESULTS: The macular holes were successfully closed in both eyes. The patient's
      best-corrected Snellen visual acuity improved from 20/60-2 to 20/30-1 in the
      right eye and from 20/70-1 to 20/40-1 in the left eye at 6 months of
      postoperative follow-up. CONCLUSION: Bilateral lamellar macular holes are rare
      occurrences in patients with retinitis pigmentosa; improved visual and anatomical
      outcomes can result after surgical intervention.

PMID- 26200385
TI  - FEEDER VESSEL LASER PHOTOCOAGULATION FOR IDIOPATHIC, SUBFOVEAL POLYPOIDAL
      CHOROIDAL VASCULOPATHY NOT RESPONDING TO EITHER ANTI-VASCULAR ENDOTHELIAL GROWTH
      FACTOR THERAPY OR PHOTODYNAMIC THERAPY.
AB  - PURPOSE: To describe the management of a subfoveal polypoidal choroidal
      vasculopathy case refractory to antiangiogenic treatment and to photodynamic
      therapy. METHODS: Case report. A 65-year-old male patient presented with a
      diagnosis of exudative age-related macular degeneration of his left eye and
      unsuccessful response to eight antiangiogenic injections. Visual acuity was
      20/33. Fluorescein angiography, spectral domain optical coherence tomography, and
      indocyanine green angiography confirmed the diagnosis of polypoidal choroidal
      vasculopathy. Two photodynamic therapy sessions along with two ranibizumab
      injections were performed, but no response was obtained. Identification and
      photocoagulation of the polyp feeder vessels was performed. RESULTS: Polypoidal
      structures regressed, intraretinal and subretinal exudation resolved, and visual
      acuity was preserved with no adverse events. CONCLUSION: Indocyanine green
      angiography-guided feeder vessel diode laser photocoagulation in selected cases
      of polypoidal choroidal vasculopathy may be considered an effective alternative
      therapy, especially in those refractory to both photodynamic therapy and
      antiangiogenic therapy.

PMID- 26200386
TI  - MACULAR HOLES, VITELLIFORM LESIONS, AND MIDPERIPHERAL RETINOSCHISIS IN ALPORT
      SYNDROME.
AB  - PURPOSE: To describe the retinal findings in two cases of Alport syndrome.
      METHODS: Observational case series. The clinical findings of the two patients
      were documented with color fundus photography and high resolution spectral domain
      optical coherence tomography. RESULTS: Patient 1 was found to have fleck
      retinopathy in both eyes, inner retinal thinning in the right eye and a full
      thickness macular hole in the left eye. Patient 2 was found to have a full
      thickness macular hole in the right eye as well as retinoschisis in the temporal
      macula in the right eye. The left eye revealed inner retinal thinning involving
      the fovea, a vitelliform lesion of the temporal macula and midperipheral
      retinoschisis involving multiple retinal layers. CONCLUSION: Retinal
      abnormalities including fleck retinopathy, retinal thinning, macular holes,
      retinoschisis, and vitelliform lesions are variably present in Alport syndrome.
      This is only the second report of a vitelliform lesion in a patient with Alport
      syndrome and the first report of midperipheral retinoschisis. The array of
      retinal findings is believed to reflect a dysfunctional Type IV collagen present
      in the internal limiting membrane and Bruch membrane.

PMID- 26200387
TI  - BILATERAL ISOLATED CHOROIDAL MELANOCYTOSIS.
AB  - PURPOSE: To report a very rare case of bilateral isolated choroidal
      melanocystosis. METHODS: Clinical case report and literature review. RESULTS: A
      24-year-old asymptomatic African American woman presented with bilateral diffuse
      choroidal pigmentation. The diagnosis of bilateral isolated choroidal
      melanocytosis was made, and optical coherence tomography was remarkable for
      increased choroidal thickness with a normal inner and outer retina. CONCLUSION:
      Although extremely rare, bilateral isolated choroidal melanocytosis may occur in
      young patients, as well as in those who are African American. Longer follow-up of
      this case and those in the literature will elucidate whether these choroidal
      lesions enlarge or have a risk of developing uveal melanoma.

PMID- 26200388
TI  - MACULAR PIGMENT RINGS AS THE PRESENTING FINDING OF MITOCHONDRIAL MYOPATHY,
      ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKELIKE EPISODES.
AB  - PURPOSE: To show the multimodal imaging findings observed in a patient in whom
      the recognition of characteristic pigmentary retinopathy led to the diagnosis of
      mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes.
      METHODS: Retrospective case report. A 47-year-old woman was referred for
      evaluation of macular changes detected on a routine ophthalmologic examination.
      RESULTS: Funduscopic examination showed bilateral findings of the focal areas of
      pigment hyperplasia in the paramacular region, forming a ringlike pattern in both
      eyes. Multimodal imaging was performed to further characterize the fundus
      changes. A review of systems revealed hearing difficulties and neurologic
      symptoms that further raised a suspicion for retinopathy associated with
      mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes
      syndrome. Genetic testing showing the mitochondrial DNA A3243G point mutation
      confirmed the diagnosis. CONCLUSION: Multimodal imaging is a useful technique in
      diagnosing retinopathy associated with the mitochondrial DNA A3243G point
      mutation. Characteristic pigmentary retinopathy with suggestive systemic findings
      should prompt genetic testing for this mutation.

PMID- 26200390
TI  - CO-Releasing Polymers Exert Antimicrobial Activity.
AB  - Infectious diseases remain one of the leading causes of death worldwide despite
      the tremendous effort devoted to the design and development of antimicrobial
      agents. However, the decrease in the effectiveness of some antibiotics is often
      associated with the development of drug resistance by pathogen. This leads to an
      urgent need for the development of new therapeutic approaches that can overcome
      the development of drug resistance. Recent evidence suggests that the biological
      signaling molecule carbon monoxide (CO) presents remarkable antimicrobial
      properties. Herein, we report the design and synthesis of a new type of water
      soluble CO-releasing polymer with antimicrobial activity against Pseudomonas
      aeruginosa that is highly efficient at preventing biofilm formation. 

PMID- 26200391
TI  - A novel phosphodiesterase-5 Inhibitor: Yonkenafil modulates neurogenesis, gliosis
      to improve cognitive function and ameliorates amyloid burden in an APP/PS1
      transgenic mice model.
AB  - In Alzheimer's disease (AD), activated microglia invade and surround beta-amyloid
      plaques, possibly contributing to the aggregation of amyloid beta (Abeta), which
      affect the survival of neurons and lead to memory loss. Phosphodiesterase-5 (PDE
      5) inhibitors have recently been shown a potential therapeutic effect on AD. In
      this study, the effects of yonkenafil (yonk), a novel PDE-5 inhibitor, on
      cognitive behaviors as well as the pathological features in transgenic AD mice
      were investigated. Seven-month-old APP/PS1 transgenic mice were treated with yonk
      (2, 6, or 18 mg/kg, intraperitoneal injection (i.p.)) or sildenafil (sild) (6
      mg/kg, i.p.) daily for 3 months and then behavioral tests were performed. The
      results demonstrated that yonk improved nesting-building ability, ameliorated
      working memory deficits in the Y-maze tasks, and significantly improved learning
      and memory function in the Morris water maze (MWM) tasks. In addition, yonk
      reduced the area of Abeta plaques, and inhibited over-activation of microglia and
      astrocytes. Furthermore, yonk increased neurogenesis in the dentate granule brain
      region of APP/PS1 mice, indicated by increased BrdU(+)/NeuN(+) and BrdU(+)/DCX(+)
      cells compared to vehicle-treated transgenic mice. These results suggest that
      yonk could rescue cognitive deficits by ameliorated amyloid burden through
      regulating APP processing, inhibited the over-activation of microglia and
      astrocytes as well as restored neurogenesis.

PMID- 26200392
TI  - First records of preorbital gland opening in rare wild barasingha (Rucervus
      duvaucelii) in social contexts may help to explain this phenomenon in cervids.
AB  - The opening of the preorbital gland in deer serves as a visual communication and
      has been linked to a wide variety of behavioural situations. As we reported
      recently, all previous long-term studies on preorbital gland opening were carried
      out on only one species, whereas case reports on six other rarely studied species
      have shown associations with different behaviours, thus greatly increasing our
      overall understanding of the real function of this gland in animal visual
      communication. Here, we report for the first time preorbital gland opening in the
      barasingha (Rucervus duvaucelii) in social contexts as observed in a wild
      population in Kanha National Park, India. We observed this behaviour in two
      different contexts: agonistic and sexual. Moreover, our record of preorbital
      gland opening during copulation is the first one amongst cervids. Our findings of
      preorbital gland opening in both contexts in wild barasingha indicate that the
      gland was opened only when the individual was highly excited. We suggest that
      preorbital gland opening may be an important behavioural indicator of an
      individual involved in a serious intraspecific interaction, and thus a useful
      tool with which to distinguish between playful and serious behaviours, especially
      in agonistic and sexual situations. 

PMID- 26200393
TI  - Saving the best for last: Differential usage of impaled prey by red-backed shrike
      (Lanius collurio) during the breeding season.
AB  - We compared the prey composition of the red-backed shrike's (Lanius collurio)
      larders in agricultural habitats in Italy, France and Poland. This species
      exhibits the behaviour of impaling prey in larders, a behaviour attributed not
      only to storing food, but also as a social indication for sexual selection and/or
      demarcation of territories. A total of 426 impaled items were identified in 244
      larders. Most common prey were identified for each country: Insecta (Hymenoptera)
      in Italy, Amphibia, Insecta (Diptera) and Clitellata in Poland, and Insecta
      (Orthoptera, Lepidoptera) in France. We found no relationship between type of
      prey impaled and height of impalement, however, we noted a negative relationship
      between the height of impalement and the distance to the nearest road.
      Furthermore, impaled toxic prey were found in all three countries, strengthening
      the possibility that prey are exposed to expedite the degradation of toxins or
      used as a social signal. Our results showed that the average weight of impaled
      prey was greater during the last reproductive stage (hatching and feeding young),
      providing evidence of differential usage of impaled prey during the breeding
      season. We therefore hypothesize that larger animals provide more energy, then
      vertebrates are preferred to invertebrates, especially when parents are feeding
      their nestlings. 

PMID- 26200394
TI  - Rats are optimal in a choice task in which pigeons are not.
AB  - In an extensive list of studies, it has been found that pigeons prefer an
      alternative associated with discriminative stimuli over another associated with
      non-discriminative stimuli, even when the probability of reinforcement is higher
      in the latter. This behavior has been named "suboptimal choice". In the present
      experiment, we evaluated whether rats, another widely studied species within the
      Experimental Analysis of Behavior, also shows this behavior. We systematically
      replicated the procedure employed with pigeons, and found that rats are not
      suboptimal, i.e., they prefer the non-discriminative alternative associated with
      .5 probability of reinforcement, over the discriminative alternative associated
      with .2 probability of reinforcement. This effect occurred even though rats
      discriminated the contingencies of reinforcement associated with each stimulus,
      suggesting that rats' optimal choice was driven by the overall probability of
      reinforcement of each alternative. Different procedural details are offered as
      possibilities for explaining this apparent inter-species difference. 

PMID- 26200395
TI  - Experimental models for cancellous bone healing in the rat.
AB  - BACKGROUND AND PURPOSE: Cancellous bone appears to heal by mechanisms different
      from shaft fracture healing. There is a paucity of animal models for fractures in
      cancellous bone, especially with mechanical evaluation. One proposed model
      consists of a screw in the proximal tibia of rodents, evaluated by pull-out
      testing. We evaluated this model in rats by comparing it to the healing of empty
      drill holes, in order to explain its relevance for fracture healing in cancellous
      bone. To determine the sensitivity to external influences, we also compared the
      response to drugs that influence bone healing. METHODS: Mechanical fixation of
      the screws was measured by pull-out test and related to the density of the new
      bone formed around similar, but radiolucent, PMMA screws. The pull-out force was
      also related to the bone density in drill holes at various time points, as
      measured by microCT. RESULTS: The initial bone formation was similar in drill
      holes and around the screw, and appeared to be reflected by the pull-out force.
      Both models responded similarly to alendronate or teriparatide (PTH). Later, the
      models became different as the bone that initially filled the drill hole was
      resorbed to restore the bone marrow cavity, whereas on the implant surface a thin
      layer of bone remained, making it change gradually from a trauma-related model to
      an implant fixation model. INTERPRETATION: The similar initial bone formation in
      the different models suggests that pull-out testing in the screw model is
      relevant for assessment of metaphyseal bone healing. The subsequent remodeling
      would not be of clinical relevance in either model.

PMID- 26200396
TI  - Bisabolane-Type Sesquiterpenoids from the Whole Plant of Parasenecio rubescens.
AB  - Twenty-two new highly oxygenated bisabolane-type sesquiterpenoids, pararubin A-V
      (1-22), were isolated from the whole plant of Parasenecio rubescens. The
      structure determination of 1-22, including the assignment of their relative
      configurations, was accomplished by extensive 1D and 2D NMR spectroscopy. The
      absolute configuration of pararubin A (1) was established by single-crystal X-ray
      crystallographic analysis. The isolated compounds were evaluated for their
      cytotoxic effects against three cancer cell lines (B16 mouse melanoma cells,
      HepG2 human hepatocellular carcinoma cells, and MCF7 human breast adenocarcinoma
      cells) and for their antimicrobial effects against Staphylococcus aureus,
      Escherichia coli, and Monilia albicans. 

PMID- 26200397
TI  - Eruption on the dorsal hand.

PMID- 26200398
TI  - Selective steroid receptor modulators in reproductive medicine.
AB  - A key step forward in the treatment of hormone-dependent diseases has been made
      since the discovery of tissue-specific steroid receptor modulators (SRMs), or
      receptor ligands that elicit agonistic or antagonistic effects in a cell- and
      tissue-dependent manner. In reproductive medicine, selective estrogen receptors
      modulators (SERMs) and selective progesterone receptors modulator (SPRMs) were
      discovered and developed since the 1970s. SERMs were first released for the
      treatment of infertility and later developed in areas such as osteoporosis
      prevention and breast cancer treatment. The later discovery of SPRMs has provided
      molecules active on the inhibition of ovulation, on the endometrium and on
      leiomyoma cells, which are currently being developed for their antiproliferative
      effects in breast cancer and endometriosis. New molecules and new routes of
      administration of SERMs and SPRMs are in development for cancer treatment, long
      term contraception and endometriosis. Based on the future advancements on the
      understanding of the mechanisms of action of these compounds, it is to be
      expected that future SRMs will emerge for newer indications. 

PMID- 26200399
TI  - Distraction lengthening of the proximal phalanx in distal thumb amputations.
AB  - OBJECTIVE: Thumb amputation is a major cause of hand dysfunction, and the
      treatment for distal thumb amputations remains controversial. Although finger
      reconstruction methods using distraction lengthening are known to restore finger
      length and function, we found no reports in the literature regarding phalangeal
      lengthening in thumb amputations. We aimed to evaluate proximal phalangeal
      lengthening in thumb amputations at or near the interphalangeal (IP) joint.
      METHODS: We retrospectively evaluated patients who had undergone distraction
      lengthening of the proximal phalanx of the thumb. All patients underwent
      osteotomy, either during the initial procedure or as a second-stage procedure.
      Distraction began 10 days after osteotomy with the use of an external fixator
      that remained in place until ossification of the gap occurred without bone
      grafting. Patients were evaluated using the QuickDASH score. RESULTS: Fourteen
      patients with a mean age of 27 years and a mean follow-up period of 7 years were
      enrolled. The mean phalangeal lengthening achieved was 20 mm. Ossification
      occurred at all distraction sites, and the fixators were maintained for a mean of
      85 days. The mean healing index was 42.5 days/cm. All 14 patients achieved the
      desired amount of phalangeal lengthening without major complications such as
      nonunion, premature union, or gross infection. CONCLUSION: For reconstruction in
      cases of distal thumb amputations, distraction lengthening of the proximal
      phalanx can be used to improve absolute length, web space, and grip distance. The
      technique is safe and effective, improves functionality/cosmesis, and offers a
      low complication risk.

PMID- 26200400
TI  - Fracture-dislocations of the proximal ulna.
AB  - OBJECTIVE: To investigate the relationship between injury patterns,
      complications, and the functional outcomes of patients with proximal-ulna
      fracture-dislocations. METHODS: Retrospective analysis of 15 patients (10 men, 5
      women; mean age, 49.1 years; mean follow-up 49 months) with 6 anterior and 9
      posterior fracture-dislocations of the proximal ulna. The proximal ulna was
      reconstructed with plates and screws in 13 patients and tension-band wiring in 2
      patients. At the final follow-up, elbow range of motion (ROM) was measured and
      Mayo elbow scores (MEPS) were recorded. Broberg-Morrey criteria were used for
      osteoarthritis staging. RESULTS: Concomitant radial-head fracture was seen in all
      posterior fracture-dislocations. Four ligamentous injuries occurred in this
      group. All anterior dislocations had trochlear-notch fractures without associated
      injuries. Mean flexion ROM was 130.6 degrees  (100 degrees -140 degrees ) and
      mean loss of extension ROM was 12.6 degrees  (0 degrees -30 degrees ) in the
      study group. The mean MEPS score was 92.3 (70-100). Patients with posterior
      fracture-dislocations showed lower ROM and MEPS and higher level of
      osteoarthritis than patients with anterior fracture-dislocations. Recurrent
      dislocations occurred in 2 patients who had ulna fractures fixed with tension
      band wiring. CONCLUSION: Radial-head fracture and ligamentous injury are specific
      components of posterior fracture-dislocations. The injury is limited to the
      trochlear notch in anterior fracture-dislocations. Posterior fracture
      dislocations have lower functional outcomes. Proximal-ulna fractures should be
      fixed with rigid internal fixation (plate and screw) even if the fracture is a
      simple 2-part fracture.

PMID- 26200401
TI  - Percutaneous double-button fixation method for treatment of acute type III
      acromioclavicular joint dislocation.
AB  - OBJECTIVE: The aim of this study was to evaluate the functional and radiological
      results of patients treated with the percutaneous double-button technique for
      acute acromioclavicular (AC) joint dislocation. METHODS: A retrospective
      evaluation was performed of 13 patients surgically treated for acute Type III AC
      joint dislocation with the percutaneous double-button fixation method. The
      coracoclavicular (CC) distance of the affected side was compared with that of the
      healthy side on anterior-posterior radiographs obtained at the final follow-up.
      In the functional evaluation, Disabilities of the Arm, Shoulder and Hand (DASH),
      Constant, and visual analog scale (VAS) scores were used. RESULTS: The 13
      patients in the study included 12 males and 1 female with a mean age of 43.4
      years (range: 22-60 years). The mean follow-up period was 13.61 months (range: 9
      24 months). The mean CC distance on the operated side was 9.23 mm (range: 8-15
      mm), and when compared with the healthy side, no statistically significant
      difference was observed. Preoperative Constant scores of a mean of 30.3 (range:
      18-42) increased to 84.4 (range: 70-90) at the final follow-up. Preoperative DASH
      scores had a mean of 14.1 (range: 11-28) and decreased to 0.4 (range: 0-3) at the
      final follow-up (p<0.001). Mean preoperative VAS score was 6.0 (range: 5-8),
      which decreased to 0.6 (range: 0-3) at the final follow-up (p<0.001). CONCLUSION:
      The percutaneous double-button fixation technique is a safe, practical, and
      effective fixation method that can be used as an alternative to arthroscopic and
      open methods for acute Type III AC joint dislocations.

PMID- 26200402
TI  - Early surgery is feasible in patients with hip fractures who are on clopidogrel
      therapy.
AB  - OBJECTIVE: Timing of surgery in hip fracture patients using antiplatelet agents
      is a controversial issue. Clopidogrel is an antiplatelet drug widely used in the
      treatment of many diseases. In this study, we aimed to investigate the outcomes
      of early surgery in hip fracture patients using clopidogrel. METHODS: Elderly
      patients with femoral neck fractures who underwent open surgery between 2009 and
      2014 were evaluated. Two hundred and eleven patients were included in the study.
      Patients were separated into 3 groups. Group 1 was constituted of patients using
      clopidogrel who had been operated on within 48 h after admission (n=74), Group 2
      was constituted of patients using clopidogrel who had been operated on after the
      fifth day of admission (n=55), and Group 3 was constituted of patients not using
      clopidogrel who had been operated on within 48 h after admission (n=83). Length
      of hospital stay, amount of blood transfusion, rate of complication, and
      mortality rate were assessed for comparison of groups. RESULTS: Age, sex,
      preoperative hemoglobin values, and ASA scores were not different between the
      groups. Amount of blood transfusions was higher in Group 1 (p=0.023). Duration of
      hospital stay was longer in Group 2 (p<0.01), as was complication rate (25.4%)
      (p<0.01). Mortality within 30 days and within the first 3 months post-surgery was
      significantly higher in Group 2 (p=0.031, p<0.01; respectively). CONCLUSION:
      Surgery should not be postponed in hip fracture patients using clopidogrel.

PMID- 26200403
TI  - Comparison of switch-therapy modalities (enoxaparin to rivaroxaban/dabigatran)
      and enoxaparin monotherapy after hip and knee replacement.
AB  - OBJECTIVE: Prevention of deep venous thrombosis (DVT) and associated pulmonary
      embolism following major orthopedic surgeries is challenging, and there is an
      increased interest in developing new treatment strategies. We compared 2 switch
      therapy modalities-enoxaparin to rivaroxaban and enoxaparin to dabigatran-and
      enoxaparin monotherapy for preventing DVT after total knee arthroplasty (TKA) and
      total hip arthroplasty (THA). METHODS: This was a prospective, non-blinded,
      randomized controlled study. We selected 180 eligible patients out of 247
      patients undergoing TKA or THA. During the preoperative checkup, patients were
      randomized to receive either enoxaparin (enoxaparin group) or switch-therapy
      regimens, comprising enoxaparin during hospitalization and rivaroxaban
      (rivaroxaban group) or dabigatran (dabigatran group) during the outpatient
      period. All patients were evaluated for DVT using Doppler ultrasonography (USG) 6
      weeks postoperatively. The primary efficacy outcome was the prevention of
      symptomatic or Doppler ultrasonography (USG)-proven DVT, whereas the primary
      safety outcome was the incidence of bleeding during the DVT-prophylaxis period.
      RESULTS: Doppler USG at 6 weeks after surgery revealed no signs of DVT in any
      patient. During the hospitalization period, only 2 major bleeding events were
      reported (1 [1.6%] in the enoxaparin group and 1 [1.6%] in the dabigatran group).
      No major bleeding events were reported during the outpatient follow-up period in
      any group. Differences among the 3 groups regarding bleeding events were not
      statistically significant (p>0.05). CONCLUSION: When using switch-therapy
      modalities, clinicians can take advantage of the safety of enoxaparin during the
      hospitalization period and ease of use of new oral anticoagulant drugs during the
      outpatient period.

PMID- 26200404
TI  - A comparison of continuous femoral nerve block and periarticular local
      infiltration analgesia in the management of early period pain developing after
      total knee arthroplasty.
AB  - OBJECTIVE: This study aimed to compare the effects of 24-h continuous femoral
      nerve block (CFNB) and periarticular infiltration analgesia (PIA) on
      postoperative pain and functional results in the first 6 weeks after total knee
      arthroplasty (TKA). METHODS: Sixty patients who underwent unilateral TKA were
      included in this study. The patients were divided into two groups: Group A
      received CFNB and Group B received PIA. Each patient received 0.25%
      levobupivacaine and 1:100,000 epinephrine as infiltration to the posterior
      capsule. A patient-controlled analgesia (PCA) device was used for all patients,
      and 24-h tramadol usage by patients was recorded. We measured maximum range of
      motion (ROM), pain using a visual analog scale (VAS), 2-min walk test (2MWT), and
      the scores of Western Ontario and McMaster Universities Arthritis Index (WOMAC)
      and Knee Society Score (KSS). RESULTS: Compared with Group B, Group A had lower
      postoperative opioid usage (p<0.05), less pain at rest (p<0.05), less pain with
      passive motion (p<0.05), less pain with movement and after active movement
      (p<0.05), and superior passive and active ROM (p<0.05). Group A also had better
      2MWT results at 24 and 48 h after surgery (p<0.05), and superior WOMAC and KSS
      results at 6 weeks after surgery. CONCLUSION: As long as it is applied with
      infiltration analgesia to the posterior capsule, CFNB is an effective and safe
      analgesia method resulting in better postoperative patient comfort and greater
      ROM. Furthermore, it produces better results in the early postoperative period
      with a favorable side effect profile.

PMID- 26200405
TI  - Effects of intra-articular levobupivacaine, fentanyl-levobupivacaine and tramadol
      levobupivacaine for postoperative pain in arthroscopic knee surgery.
AB  - OBJECTIVE: The aim of this study was to compare the postoperative analgesic
      efficacy of intra-articularly injected levobupivacaine, levobupivacaine-fentanyl,
      and levobupivacaine-tramadol combinations. METHODS: Eighty patients scheduled for
      elective knee arthroscopy were divided randomly into 4 groups of 20 patients
      each. Group 1 (the control group) received intra-articular saline, Group 2
      received levobupivacaine 2.5 mg/ml, Group 3 received levobupivacaine 2.5 mg/ml +
      tramadol 50 mg, and Group 4 received levobupivacaine 2.5 mg/ml + fentanyl l50
      mcg. All patients were operated on under general anesthesia, and a total of 20 ml
      study solution was injected: 7 ml subcutaneously before surgery and 13 ml intra
      articularly upon completion of surgery. For postoperative, pain visual analogue
      scale (VAS) was assessed at the 1st, 2nd, 4th, 8th, 12th, and 24th hours
      postoperatively. Patients with a VAS score over 5 received diclofenac sodium, and
      the need for rescue analgesics was recorded. RESULTS: At the 1st, 2nd, 4th, 8th,
      12th, and 24th postoperative hours, Group 3 and Group 4 had statistically
      significant lower VAS scores of pain (p<0.01). Postoperative rescue analgesic
      requirements were different among the groups. The postoperative 1st hour
      analgesic requirement was statistically significantly lower in Group 3 and Group
      4 when compared to the other groups (p<0.01). At the postoperative 2nd and 4th
      hours, analgesic requirements were statistically significantly lower in Group 3
      than in the other groups (p<0.01). Analgesic requirements were statistically
      significantly lower in Group 3 and Group 4 than in the other groups (p<0.01).
      Analgesic requirements at the 12th and 24th postoperative hours did not show any
      statistically significant difference (p>0.05). CONCLUSION: The results indicated
      that levobupivacaine combined with either fentanyl or tramadol decreased rescue
      analgesic requirements when compared to levobupivacaine alone.

PMID- 26200406
TI  - Diagnostic efficacy of standard knee magnetic resonance imaging and radiography
      in evaluating integrity of anterior cruciate ligament before unicompartmental
      knee arthroplasty.
AB  - OBJECTIVE: The purpose of this study was to investigate the diagnostic efficacy
      of standard magnetic resonance imaging (MRI) and plain radiographs in determining
      the status of anterior cruciate ligament (ACL) for surgical decision-making
      processes in cases of medial unicompartmental knee arthroplasty (UKA). METHODS: A
      total of 59 knees of 36 consecutive patients who underwent knee replacement
      surgery were analyzed retrospectively. MRI scans were assessed independently by 3
      observers (radiologists), while the plain radiographs were evaluated by an
      independent radiologist. Results were compared with the intraoperative ACL
      status. Cross tabulation was used for descriptive statistics to analyze
      sensitivity, specificity, and accuracy of MRI and plain radiographs. RESULTS:
      When the same observer assessed and classified the MRI twice, the reproducibility
      of the classification system varied from moderate to excellent. However, the
      interobserver concordance was moderate. The sensitivity of MRI was 73% and the
      specificity was 81%, while the sensitivity and specificity of plain radiographs
      was 36% and 79%, respectively. The accuracy of MRI was 80%, while that of the
      radiographs was 71%. CONCLUSION: Detection of intact ACL may be possible on
      available plain radiographs without necessity for additional means such as MRI,
      which may cause increase costs and loss of time. In cases where there is
      uncertainty regarding ACL integrity in degenerative knees, although standard MRI
      provides additional information on ACL status, it is not of sufficient diagnostic
      value.

PMID- 26200407
TI  - Evaluation of mobile bearing unicompartmental knee arthroplasty, opening wedge,
      and dome-type high tibial osteotomies for knee arthritis.
AB  - OBJECTIVE: Three methods of surgery used in the treatment of knee osteoarthritis
      (OA) are mobile bearing unicompartmental knee arthroplasty (Oxford UKA), opening
      wedge high tibial osteotomy (HTO), and dome-type HTO. This article aimed to
      retrospectively compare these three methods in terms of outcomes for health
      status, patient satisfaction, and function. METHODS: Between 2003 and 2010, 255
      knees of 235 patients underwent operations for medial knee OA. Three types of
      surgery were performed. Group 1 consisted of 109 knees of 94 patients who
      underwent Oxford UKA. Group 2 was made up of 36 knees of 36 patients who
      underwent HTO using circular external fixation, and Group 3 comprised 57 knees of
      52 patients on whom opening wedge type HTO using locking plate fixation was
      performed. SF-36 and HSS knee scores were used to compare the functional outcomes
      among groups. RESULTS: Statistically significant differences were found between
      the preoperative and postoperative measures in all 3 of the treatment groups for
      physical function, physical role, pain, general health, vitality, social
      function, emotional role, and mental health according to SF-36 and HSS scores. In
      the 2nd group, the average correction of the mechanical axis deviation (MAD) was
      38 mm with 11.7o along the femorotibial axis and 6.2o along the medial proximal
      tibial angle (MPTA). In the 3rd group, the average correction in the MAD was 28
      mm with 9.7o along the femorotibial axis and 5.6o along the MPTA. All 3 of the
      treatment alternatives were observed to be sufficient. Satisfactory postoperative
      results were achieved in the UKA group in terms of social function and mental
      health, and the patients were able to achieve early rehabilitation and return to
      their previous life activities. CONCLUSION: UKA is the ideal option for patients
      who wish for the earliest possible return to social and recreational activities.

PMID- 26200408
TI  - Treatment of pathological fractures due to simple bone cysts by extended
      curettage grafting and intramedullary decompression.
AB  - OBJECTIVE: Effectiveness and morbidity of curettage grafting and intramedullary
      decompression in the treatment of pathological fractures due to simple bone cysts
      (SBCs) were evaluated. METHODS: Between 2005 and 2012, 34 children with SBCs were
      treated with extended curettage grafting and intramedullary decompression.
      Average age of the patients (23 male, 11 female) at surgery was 11.7 years
      (range: 6-21 years). The lesions were localized in the humerus (19), femur (12),
      tibia (2), and ulna (1). Pathological micro- or displaced fractures occurred in
      31 patients. Surgical procedure included extended curettage by using
      cauterization and high-speed burring, bone grafting, and intramedullary
      decompression with elastic nails. Six patients had been treated conservatively or
      surgically in other institutions previously. Radiographic and functional results
      were evaluated by Capanna criteria and MSTS scores respectively. Early and late
      complications and additional surgical procedures were recorded. RESULTS: The
      average follow-up was 37 months (range: 18-89 months). The average time to heal
      for pathological fractures was 8 weeks (range: 6-12 weeks). Radiographic
      evaluation revealed Grade 1 healing in 28 patients (82%) and Grade 2 healing in 6
      patients (18%). The average MSTS score based on final follow-up was 28.5 (range:
      17-30); excellent (32 patients; 94%) and good (2 patients; 6%) functional results
      were obtained. There was no early or late infection, refracture or implant
      failure. Malunion developed following treatment of 2 humeral and 2 femoral
      lesions. With the exception of 2 implant removals, no patients required
      additional surgical intervention. CONCLUSION: Complete cyst healing and
      satisfactory functional results can be obtained by curettage grafting and
      intramedullary decompression. This technique restores bone integrity by allowing
      early motion and prevents refracture and subsequent deformity in the majority of
      patients.

PMID- 26200409
TI  - Radiation in the orthopedic operating theatre.
AB  - OBJECTIVE: The aim of the study was to determine the amount of radiation exposure
      in the orthopedic operating theater, to show that the radiation dose was
      decreased with distance from the tube, and to inform personnel about protective
      measures. METHODS: Ionised radiation was measured in the orthopedic operating
      theater where fluoroscopy was used between 18 February 2014 and 02 June 2014.
      Four dosimeters were placed at the head and foot of the operating table and at
      200 cm from those areas at a height of 60 cm vertical to the floor. RESULTS: At
      the end of 104 days, the total values were determined as 90.5 mrem at the foot of
      the table, 68.17 mrem at the head of the table, 7.5 mrem at 200 cm from the foot
      of the table, and 5.17 mrem at 200 cm from the head of the table. A significant
      decrease was observed in the values determined at a distance from the radiation
      source. CONCLUSION: The rate of radiation determined in the dosimeters decreased
      when distance from the radiation source increased. During the use of fluoroscopy
      in orthopedic surgery, the wearing of lead aprons, neck protectors, and glasses,
      in addition to maintaining a distance from the tube, will reduce the radiation
      exposure of individuals.

PMID- 26200410
TI  - A detailed analysis of messages posted on the 'Turk-Orthopod' mailing list over a
      13-year period.
AB  - OBJECTIVE: The objective of this study was to analyze the content of the 'Turk
      Orthopod' mailing list between 2000 and 2013. METHODS: All messages posted to the
      'Turk-Orthopod' mailing list were documented and categorized by 4 orthopedic
      surgeons who were active members of the mailing list into 11 categories based on
      the content of the messages. RESULTS: A total of 15,699 messages were evaluated
      and included in the analysis. The mean number of daily messages in 2000 was 0.98
      messages/day and increased to 7.23 messages/day in 2013. The most common type of
      message was announcements (37.5%) about national or international congresses,
      conferences, symposia, meetings, and panels. The second most common type of
      message was condolence messages (11.7%). Case discussions and academic
      discussions comprised 6.3% and 4.5% of the messages, respectively. CONCLUSION:
      The 'Turk-Orthopod' mailing list serves primarily as an information board and a
      powerful social media platform for communication among Turkish orthopedic
      surgeons. However, scientific case discussions and other professional issues
      comprise a minority of the messages.

PMID- 26200411
TI  - Biomechanical comparison of headless antegrade screw versus retrograde cortical
      screw for coronoid fracture fixation.
AB  - OBJECTIVE: Posterior-to-anterior directed screws are stronger than anterior-to
      posterior directed screws for coronoid fracture fixation. Anterior approaches
      that facilitate direct reduction and fixation of coronoid fractures have been
      described. The present study was based on the hypothesis that anterior-to
      posterior headless screw (Acutrak Mini(r) 3.5 mm * 26 mm, Acumed, Hillsboro,
      Oregon, USA) fixation of coronoid fractures would be as strong as posterior-to
      anterior 2.7 mm Association for Osteosynthesis (AO) cortical screw fixation.
      METHODS: This study included 14 ulnas obtained from 14 formalin-preserved adult
      cadavers. Coronoid type 2 fractures were created and fixed randomly using
      anterior-to-posterior headless screws (antegrade group) and posterior-to-anterior
      2.7 mm AO cortical screws (retrograde group). The experimental constructs were
      loaded until 2 mm of displacement. Failure load (N), fixation stiffness (Nmm-1),
      and indentation stiffness were calculated. RESULTS: Failure load was higher in
      the retrograde screw group (p=0.03), whereas loading stiffness values of the
      fixation devices and bones did not differ between the 2 fixation groups (p>0.05).
      CONCLUSION: The present study failed to show that anterior-to-posterior directed
      headless screw fixation of coronoid fractures could adequately replace posterior
      to-anterior placed screw fixation.

PMID- 26200412
TI  - The effect of equine-derived bone protein extract (Colloss-E) in the treatment of
      cavitary bone defects: an experimental study.
AB  - OBJECTIVE: Bone protein extract (BPE) usually requires a carrier or a scaffold
      for implantation. We aimed to compare the effect of equine-derived BPE, an
      osteoinductive agent composed of a high amount of type-I collagen and other bone
      proteins (Colloss-E), with that of human demineralized bone matrix (DBM) for
      treating cavitary bone defects not requiring scaffold use. METHODS: Rabbit distal
      femoral condyle was used as a stable cavitary bone defect model. Bone defects of
      6-mm diameter and 10-12-mm depth were created in the femoral condyles. Rabbits
      were assigned into the equine-derived BPE (BPE), human-derived DBM (DBM), and
      control (C) groups. Approximately 20 mg of BPE was implanted into the defect in
      the equine-derived BPE group (n=6), whereas 0.3 cc of DBM was implanted in the
      DBM group (n=6). Defects were left empty in the C group (n=6). The defect area
      was histologically examined after 6 weeks. RESULTS: There were no instances of
      macroscopic defect collapse or failure. Histopathological examination revealed
      that the BPE group had better scores (statistically significant) than both the
      other groups in terms of quality of union. The BPE group also had higher scores
      than the DBM group in terms of graft incorporation and new-bone formation.
      CONCLUSION: The current study revealed results consistent with those of the
      previous studies concerning BPEs. Equine-derived BPE was found to be successful
      for treating cavitary bone defects not requiring scaffold use.

PMID- 26200413
TI  - Effects of hyaluronic acid (Hyalonect) on callus formation in rabbits.
AB  - OBJECTIVE: Bone fragment and graft stabilization are important during
      reconstructive surgery of cases with comminuted fractures and bone defects. We
      examined the effect of Hyalonect surgical mesh on the healing dynamics of
      metaphyseal bone defects created in rabbit tibiae. METHODS: Approximately 5-mm
      defects were created on the anterior aspect of the proximal tibial metaphysis of
      80 male rabbits. The rabbits were randomly assigned to four groups: Group I, bone
      defects left alone (control group); Group II, bone defect covered with Hyalonect;
      Group III, bone defect filled with allograft; and Group IV, bone defect filled
      with allograft and covered with Hyalonect. RESULTS: No significant histological
      differences were noted between Groups II and III or Groups III and IV at 3 and 6
      weeks. At 3 weeks, Groups II, III, and IV had significantly better healing than
      Group I (p<0.05). In addition, Group IV showed significantly better healing than
      Group II at 3 and 6 weeks. At 6 weeks, only Group IV showed better healing than
      Group I (p<0.05). Radiologically, Groups II, III, and IV showed better healing
      than Group I at 3 and 6 weeks (p<0.05). CONCLUSION: Hyalonect application and
      bone grafting significantly accelerated the healing process when used alone or
      together. Hyalonect application along with bone grafting resulted in better early
      radiological healing than bone grafting alone.

PMID- 26200414
TI  - Talar neck fractures: anatomic landmarks of suitable position for posterolateral
      screw insertion.
AB  - OBJECTIVE: The posterolateral window is a suitable position for screw insertion.
      The aim of this study was to define this position for posterolateral screw
      insertion. METHODS: Fifteen adult cadaver ankles were used in this study. When
      the ankle was positioned in a neutral position, the posterolateral window was
      exposed. Height and width of the window were measured. Vertical distance from the
      center of the window to the lateral malleolus tip (LMT), horizontal distance from
      the center of the window to the lateral of the Achilles tendon (LAT), and
      horizontal distance from the lateral of the Achilles tendon to the sural nerve
      (SN) were measured. Additionally, the anatomical relationships between the center
      of the window (the screw insertion point) and surrounding tissues were noted.
      RESULTS: The results indicated that the posterolateral window was bounded
      medially by the lateral tubercle of the posterior process of the talus (LTPT),
      laterally by the posterior border of lateral malleolar (PBLM), superiorly by the
      trochlear articular surface (TAS), and inferiorly by the posterior calcaneal
      facet (PCF). The height and width of the posterolateral window were 1.89+/-0.04
      cm and 0.91+/-0.01 cm, respectively. LMT was 0.40+/-0.01 cm, LAT was 0.19+/-0.02
      cm, and SN was 0.62+/-0.04 cm. The present data showed that posterior screw
      insertion may be a safer screw insertion technique for talar neck fractures.
      Performing the operation through the posterolateral window had no negative effect
      on surrounding tissues such as the flexor hallucis longus and posterior
      talofibular ligament tissues when the ankle joint was positioned in a neutral
      position. Additionally, the screw head should be countersunk to reduce
      intraoperative risk. CONCLUSION: The posterolateral window is a safer point for
      posterolateral screw insertion for talar neck fractures.

PMID- 26200415
TI  - Evaluation of an unusual ossicle by multi-detector computed tomography:
      Oppenheimer's ossicle.
AB  - Variations and anomalies of the neural arch result from alterations in the
      ossification process. Absence of lumbar articular process is a rare anomaly which
      most commonly involves the inferior articular process of the L4 or L5 vertebrae.
      Non-union at the tip of the articular process is a more common variation, known
      as Oppenheimer's ossicle. In this case report, we present multi-detector computed
      tomography findings of Oppenheimer's ossicles in 2 separate cases. 

PMID- 26200416
TI  - Hand injury with a nail gun: a case report with literature review.
AB  - The nail gun was introduced in the late 1950s to increase the ease of driving
      nails, studs, bolts, or staples into various hard surfaces. The nail gun is a
      potentially dangerous device that is still commonly used in the construction
      industry. Since its introduction, an increasing number of studies have reported
      injuries associated with nail guns. Nail gun-related injuries-such as to the
      head, neck, and chest-can be devastating, and in some cases, even fatal.
      Extremity injuries, notably in the hand, can cause loss of function, missed work,
      and long-term health effects. This case report describes a nail-gun injury of the
      hand along with a discussion of the unique features of and treatment strategies
      for nail gun injuries. 

PMID- 26200417
TI  - Rhabdomyolysis after tourniquet use in proximal tibial osteotomy: a case report
      and review of the literature.
AB  - Rhabdomyolysis following pneumotic tourniquet use is an extremely rare
      complication. In this case report, we aimed to present an unusual tourniquet
      complication following proximal tibial osteotomy. A 55-year-old female patient
      was operated on for genu varum in our clinic. Postoperatively, an anuria
      developed, and liver and kidney function test levels increased. The patient was
      diagnosed with acute rhabdomyolysis, and an aggressive treatment was begun. 

PMID- 26200418
TI  - The effect of red cell distribution width on mortality in partial hip replacement
      surgery.

PMID- 26200419
TI  - Authors' reply: the effect of red cell distribution width on mortality in partial
      hip replacement surgery.

PMID- 26200420
TI  - [Relationship between pre-dialysis period and mortality and morbidity; the
      importance of timely pre-dialysis care].
AB  - OBJECTIVE: To investigate if the duration of pre-dialysis nephrology care is a
      predictive factor for mortality and morbidity in the first year of renal
      replacement therapy (RRT). DESIGN: Cohort study. METHOD: We included all patients
      with chronic or acute-on-chronic renal failure whose estimated glomerular
      filtration time (eGFR) was < 30 ml/min/1.73 m2 6 months before starting RRT and
      in whom RRT was initiated in 2005-2006 or 2009-2010. Depending on the duration of
      the pre-dialysis period we allocated patients to the short (< 6 months) or the
      long (>= 6 months) pre-dialysis group. Data regarding mortality and morbidity
      were registered at the initiation of RRT (T0), after 3 (T3), 6 (T6) and 12 (T12)
      months. RESULTS: Thirty-nine patients with a short pre-dialysis period and 49
      patients with a long pre-dialysis period were included. Patients with a short pre
      dialysis period had higher mortality (T6: 23.1% vs. 8.2%; p = 0.05), more
      hospital stays (2 vs. 1 stay; p = 0.02), and longer hospital stays (16 vs. 3
      days; p < 0.01). Additionally, in this group RRT more often had to be started
      through an acute route of administration for dialysis, which was associated with
      a higher mortality at T6 (23.8% vs. 6.5%; p = 0.02). CONCLUSION: A too short pre
      dialysis period is predictive for higher mortality and morbidity in the first
      year after initiation of RRT. The necessity for an acute route of administration
      for dialysis seems to be the most important predictor.

PMID- 26200421
TI  - [Constitutional mismatch repair deficiency syndrome].
AB  - BACKGROUND: Constitutional mismatch repair deficiency (CMMR-D) syndrome is
      characterised by a significantly increased risk for developing cancer in
      childhood. It arises when both parents have a mutation in the same mismatch
      repair gene and pass it on to their child. CASE DESCRIPTION: An 8-year-old girl
      was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age
      of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple
      hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of
      11. CONCLUSION: In children with cancer CMMR-D syndrome can be recognized
      particularly if there are multiple primary malignancies and skin
      hyperpigmentations and hypopigmentations. The parents of these children are at
      high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.

PMID- 26200422
TI  - [A man with a painful upper arm after bench press exercise].
AB  - A 22-year-old male bodybuilder presented with pain and a haematoma of his right
      upper arm after bench press exercises. Suspicion of a pectoralis muscle tear was
      confirmed by MRI and surgical repair was performed. Ruptures of the pectoralis
      major muscle are rare, but may occur in young male bodybuilders, typically after
      bench press exercises. 

PMID- 26200423
TI  - [Muller-Weiss disease: idiopathic avascular necrosis of the navicular bone].
AB  - BACKGROUND: Muller-Weiss disease is a rare and complex foot disorder. The
      underlying aetiology of this condition involves abnormal loading of the navicular
      bone combined with delayed ossification. Muller-Weiss disease is progressive and
      ultimately results in deformation and fragmentation of the navicular bone with
      plantar-flexed hindfoot varus. In patients with a severe form of this foot
      deformity, treatment involves arthrodesis of the midfoot with bridging of the
      navicular bone. CASE DESCRIPTION: A 43-year-old female patient was seen in our
      outpatient clinic with pain in her right foot. Her symptoms had been present for
      seven months and had developed spontaneously without prior trauma. Imaging
      investigations resulted in the diagnosis of Muller-Weiss disease in both her
      right and her left foot. CONCLUSION: It is important to recognize this condition
      at an early stage so that patients can receive conservative treatment initially.

PMID- 26200424
TI  - [Switching to e-cigarettes affects drug concentration].
AB  - BACKGROUND: Cytochrome P450 subtype 1A2 (CYP1A2) is responsible for the
      metabolism of several drugs, including the antipsychotic agent clozapine. Smoking
      cigarettes induces CYP1A2. Due to this induction, a higher dosage of the drug is
      required by patients who smoke tobacco. CASE DESCRIPTION: The dosage of clozapine
      was changed for a 34-year-old male because of suspected active psychosis.
      However, serum levels of clozapine did not change according to expectations. It
      appeared that the patient had switched from smoking normal cigarettes to using e
      cigarettes and then started smoking cigarettes again during the time of the
      dosage change. This gave a plausible explanation for the observed clozapine
      concentrations. CONCLUSION: When patients switch from smoking normal cigarettes
      to using e-cigarettes induction of the CYP1A2 enzyme stops. A switch of this type
      may result in a major, undesirable increase in drug concentrations. Doctors
      should be alert to this when prescribing medication metabolised by CYP1A2 with a
      narrow therapeutic window.

PMID- 26200425
TI  - [A neonate with ambiguous genitalia].
AB  - In a neonate with ambiguous genitalia, physical examination revealed a phallus.
      Ultrasonography showed a vagina and uterus, but no gonads. Because of severe
      undervirilisation in the presence of a uterus, probably due to 46,XY gonadal
      dysgenesis, parents were advised female sex assignment. When after a few weeks
      the phallus had increased in size, abdominal laparoscopy showed an underdeveloped
      uterus. Gonadal biopsy confirmed gonadal dysgenesis. Sex assignment was
      reconsidered and changed into the male gender. 

PMID- 26200426
TI  - [The forgotten capitulation of evidence-based medicine].
AB  - In 1992, the Canadian physician Gordon Guyatt wrote an article that is generally
      regarded as the starting point of evidence-based medicine (EBM). He described the
      ideas behind the McMaster residency programme for 'evidence-based practitioners',
      founded by David Sackett. Eight years later, in 2000, Guyatt concluded that this
      programme was too ambitious. In a new publication he described most doctors as
      'evidence-users'. This editorial marks the transition from an individual to a
      collective form of EBM, emphasizing the use of evidence-based guidelines. The
      starting point of this collective form of EBM is not the well-known 1992 paper,
      but the forgotten editorial in 2000, which was described by Guyatt's colleagues
      as the capitulation of EBM. 

PMID- 26200427
TI  - [Timely referral for predialysis; multiple players in the field].
AB  - Timely referral is essential in patients with end-stage renal disease. Time is
      needed to inform the patient on the options of dialysis or kidney transplantation
      and for the placement of arteriovenous fistulae if haemodialysis is indicated;
      early referral is associated with lower morbidity and mortality. A prerequisite
      for timely referral is that patients with chronic kidney disease are recognised,
      which involves the following factors: chronic kidney disease should be mentioned
      in the patient's history; the patient should be informed of the diagnosis; and
      patients, general practitioners, pharmacists and specialists should have
      knowledge of the risk factors for acute-on-chronic kidney disease. Timely
      referral for predialysis requires optimal collaboration between the patient and
      many health care professionals. 

PMID- 26200429
TI  - [Prevalence and Comorbidity of Self-Reported Diagnosis of Burnout Syndrome in the
      General Population - Results of the German Health Interview and Examination
      Survey for Adults (DEGS1)].
AB  - Objective: To determine the prevalence and comorbid mental disorders of self
      reported diagnosis of burnout syndrome in the general population of Germany.
      Methods: In the German Health Interview and Examination Survey (DEGS1) self
      reported diagnosis of a burnout syndrome made by a physician or psychotherapist
      was assessed in a standardized interview (N = 7987). For N = 4483 mental
      disorders were determined with the Composite International Diagnostic Interview
      (CIDI). Weighted lifetime and 12-month prevalences were calculated. Results:
      Lifetime prevalence of diagnosed burnout syndrome was 4.2 % (women 5.2 %, men 3.3
      %), 12-month prevalence was 1.5 % (women 1.9 %, men 1.1 %). Highest prevalences
      were found in 40 - 59 year olds, in people with middle and high socio-economic
      status and in women with low and men with high social support. Among the 12-month
      cases, 70.9 % had at least one DSM-IV disorder. Associations were found for the
      diagnosis of burnout syndrome with somatoform, affective and anxiety disorders.
      Conclusion: The diagnosis of burnout syndrome is less frequently given and
      reported than expected. People with a burnout diagnosis often have a manifest
      mental disorder.

PMID- 26200428
TI  - Viral dark matter and virus-host interactions resolved from publicly available
      microbial genomes.
AB  - The ecological importance of viruses is now widely recognized, yet our limited
      knowledge of viral sequence space and virus-host interactions precludes accurate
      prediction of their roles and impacts. In this study, we mined publicly available
      bacterial and archaeal genomic data sets to identify 12,498 high-confidence viral
      genomes linked to their microbial hosts. These data augment public data sets 10
      fold, provide first viral sequences for 13 new bacterial phyla including
      ecologically abundant phyla, and help taxonomically identify 7-38% of 'unknown'
      sequence space in viromes. Genome- and network-based classification was largely
      consistent with accepted viral taxonomy and suggested that (i) 264 new viral
      genera were identified (doubling known genera) and (ii) cross-taxon genomic
      recombination is limited. Further analyses provided empirical data on
      extrachromosomal prophages and coinfection prevalences, as well as evaluation of
      in silico virus-host linkage predictions. Together these findings illustrate the
      value of mining viral signal from microbial genomes. 

PMID- 26200430
TI  - Aortic stenting.
AB  - The approach to aortic pathology is nowadays more and more endovascular at both
      thoracic and abdominal levels. Thoracic stenting has gained worldwide acceptance
      as first intention to treat pathologies of the descending thoracic aorta.
      Indications have been extended to aortic arch aneurysms and also to diseases of
      the ascending aorta. The current devices in use for thoracic endovascular repair
      (TEVAR) are Medtronic Valiant, Gore TAG, Cook Tx2 and Jotec. The choice of the
      endograft depends on the thoracic aortic pathology and the anatomical
      suitability. The technological evolution of the abdominal aortic endografts was
      very rapid, arriving now at the fourth generation. We report the results of 55
      elective cases of endovascular abdominal aortic repair (EVAR) performed in two
      vascular surgical centers in Romania and Germany. The prostheses used were 16 E
      vita Abdominal XT, 12 Excluder, eight Talent, seven PowerLink, three Endurant and
      nine custom-made, fenestrated or branched from Jotec. The mean follow-up was 18
      months with CT-scan, duplex ultrasound and contrast-enhanced ultrasound. The
      mortality was 2%. EVAR tends to become the gold standard for abdominal aortic
      aneurysm repair. Technological development of the devices with lowest profile
      introduction systems will permit to extend the anatomical indications to new
      frontiers. 

PMID- 26200432
TI  - Two Compounds Constructed from Bimolybdenum-Capped Sandwich-Type Tetra-Ni
      molybdogermanate and N-Donor Multidentate Ligand.
AB  - Two organic-inorganic hybrid bimolybdenum-capped tetra-Ni(II) sandwich-type
      molybdogermanates, namely, (H2L)4[Ni4(H2O)2{B-alpha-GeMo9O34 (MoO2)}2].6H2O (1),
      [Ni2(HL)4(H2O)2][Ni4(H2O)2{B-alpha-GeMo9O34(MoO2)}2].12H2O (2), L = 2,4,5-tri(4
      pyridyl)imidazole, were prepared with hydrothermal synthesis method and
      characterized by elemental analysis, IR spectroscopy, powder X-ray diffraction,
      thermogravimetric analysis, and single-crystal X-ray diffraction. Their magnetic
      properties and electrochemical properties were investigated. The results show
      that compounds 1 and 2 contain a new bimolybdenum-capped sandwich-type
      heteropolymolybdate anion, [Ni4(H2O)2{B-alpha-GeMo9O34(MoO2)}2](8-). The compound
      1 is a zero-dimensional supramolecular compound, and the supramolecular
      architecture of compound 2 is constructed from covalent layers through hydrogen
      bonds and pi-pi interaction. The two compounds both present electrocatalytic
      activities for the reduction of nitrite. 

PMID- 26200433
TI  - Evidence, discovery and justification: the case of evidence-based medicine.
AB  - The purpose of this paper is to develop some thoughts on philosophical issues
      surrounding evidence-based medicine (EBM), especially related to its
      epistemological dimensions. After considering the scope of several philosophical
      concepts that are relevant to the discussion, and drawing some distinctions among
      different aspects of EBM, we evaluate the status of EBM and suggest that EBM is
      mainly a meta-methodology. Then, we outline an evaluation of the thesis that EBM
      is a 'new paradigm' in the practice of medicine. We argue that EBM does not seem
      to have arisen in the way Kuhn imagined paradigms to arise but as a conscious,
      deliberate proposal, more as programme than as a reality. Furthermore, there is
      something paradoxical about appealing to evidence or to the best evidence as a
      way of promoting a new paradigm. For the proposal seems to assume that there is
      something that by its own virtue is the best evidence for a given time. But this
      idea would have been rejected by Kuhn. If EBM involves a genuine new alternative
      in the field of medicine and shows a way in which the discipline will endure
      henceforth, this indicates that it is not what Kuhn once called a 'paradigm' and
      even, paradoxically, it is good evidence that scientific paradigms do not exist,
      at least in medicine. 

PMID- 26200431
TI  - 227 Views of RNA: Is RNA Unique in Its Chemical Isomer Space?
AB  - Ribonucleic acid (RNA) is one of the two nucleic acids used by extant
      biochemistry and plays a central role as the intermediary carrier of genetic
      information in transcription and translation. If RNA was involved in the origin
      of life, it should have a facile prebiotic synthesis. A wide variety of such
      syntheses have been explored. However, to date no one-pot reaction has been shown
      capable of yielding RNA monomers from likely prebiotically abundant starting
      materials, though this does not rule out the possibility that simpler, more
      easily prebiotically accessible nucleic acids may have preceded RNA. Given
      structural constraints, such as the ability to form complementary base pairs and
      a linear covalent polymer, a variety of structural isomers of RNA could
      potentially function as genetic platforms. By using structure-generation
      software, all the potential structural isomers of the ribosides (BC5H9O4, where B
      is nucleobase), as well as a set of simpler minimal analogues derived from them,
      that can potentially serve as monomeric building blocks of nucleic acid-like
      molecules are enumerated. Molecules are selected based on their likely stability
      under biochemically relevant conditions (e.g., moderate pH and temperature) and
      the presence of at least two functional groups allowing the monomers to be
      incorporated into linear polymers. The resulting structures are then evaluated by
      using molecular descriptors typically applied in quantitative structure-property
      relationship (QSPR) studies and predicted physicochemical properties. Several
      databases have been queried to determine whether any of the computed isomers had
      been synthesized previously. Very few of the molecules that emerge from this
      structure set have been previously described. We conclude that ribonucleosides
      may have competed with a multitude of alternative structures whose potential
      proto-biochemical roles and abiotic syntheses remain to be explored.

PMID- 26200434
TI  - A Linear trans-Bis(imido) Neptunium(V) Actinyl Analog:
      Np(V)(NDipp)2((t)Bu2bipy)2Cl (Dipp = 2,6-(i)Pr2C6H3).
AB  - The discovery that imido analogs of actinyl dioxo cations can be extended beyond
      uranium into the transuranic elements is presented. Synthesis of the Np(V)
      complex, Np(NDipp)2((t)Bu2bipy)2Cl (1), is achieved through treatment of a Np(IV)
      precursor with a bipyridine coligand and lithium-amide reagent. Complex 1 has
      been structurally characterized, analyzed by (1)H NMR and UV-vis-NIR
      spectroscopies, and the electronic structure evaluated by DFT calculations. 

PMID- 26200435
TI  - Critical Care Functional Rehabilitation Outcome Measure: developing a validated
      measure.
AB  - INTRODUCTION: In 2009, the National Institute for Health and Clinical Excellence
      (NICE) developed guidelines, which recognized that rehabilitation plays a vital
      role in recovery from illness and in returning patients to their previous
      activity levels. NICE recommended the use of valid and reliable "outcome
      measures" as an evaluation tool. AIM: To develop and evaluate the validity and
      reliability of a new Critical Care Functional Rehabilitation Outcome Measure
      (CcFROM). METHOD: The CcFROM was developed by physiotherapists working within the
      authors' institution and was based on an evaluation of current measures. Face and
      content validity were investigated using a questionnaire posted to 21
      physiotherapists. Same-day and between-day intra-rater reliability and inter
      rater reliability were investigated by three physiotherapists viewing 20
      physiotherapy rehabilitation sessions and completing the CcFROM. Data were
      analysed for relative and absolute reliability. RESULTS: The questionnaire
      demonstrated very high face validity and moderate content validity. 43% of the
      physiotherapists also suggested including an upper limb activity. Clinically
      acceptable same-day and between-day intra-rater reliability was demonstrated with
      ICCs of 0.985 (CI, 0.968-0.993) and 0.985 (CI, 0.871-0.972), respectively. Inter
      rater reliability was recorded with an ICC of 0.906 (CI: 0.816-0.959).
      CONCLUSION: This study has shown that the CcFROM is a valid and reliable outcome
      measure for use in Critical Care.

PMID- 26200436
TI  - Beliefs towards mental illness in Turkish physiotherapy students.
AB  - Mental health is a new area of specialization for physiotherapists. However, they
      usually meet patients with psychiatric co-morbidities secondary to other chronic
      diseases. It is important to explore the beliefs of future physiotherapists
      regarding mental illness in order to implement effective strategies to avoid
      possible stigmatizing attitudes that may interfere with the rehabilitation
      process. Moreover, the psychiatric field should be introduced to physiotherapists
      as a clinical and research area. Therefore, we aimed to question the beliefs of
      physiotherapy students regarding mental illness using the Beliefs towards Mental
      Illness Scale in two different universities in Turkey. The total score of 524
      students was 46.5 +/- 14.5 out of 105 while the Dangerousness Subscale score was
      21.2 +/- 5.8/40; Incurability and Poor Social and Interpersonal Skills Subscale
      score was 24.2 +/- 9.3/55 and Shame Subscale score was 1.1 +/- 1.9/10. Students
      who had a relationship with an individual having a mental problem and students
      who had consulted a psychiatrist/psychologist for any mental problem showed more
      positive beliefs. Future physiotherapists should be informed and trained
      regarding people with mental illness both to avoid stigma and to be aware of this
      area in physiotherapy settings. Therefore, it is important to implement new
      curricula for schools providing physiotherapy education including courses,
      lectures and clinical practices in the psychiatry field.

PMID- 26200437
TI  - Performance on a test of rapid stepping in community-dwelling older adults:
      validity, relative and absolute reliability and minimum detectable change.
AB  - Reduced stepping speed is associated with balance deficits and falls in older
      adults. We evaluated psychometric properties of a test of rapid stepping, the
      Thirty-Rapid-Step test (30-RST) in 37 community-dwelling older adults.
      Participants performed the 30-RST, dynamic (step execution time, five-times-sit
      to-stand test, gait speed, maximum step length and four-square-step test) and
      static (single-leg-stance-time and postural sway) performance-based tests.
      Relationships between 30-RST and performance-based tests were evaluated with
      Spearman's rho. Intraclass correlation coefficient (ICC), standard error of
      measurement (SEM), 95% limits of agreement and minimum detectable change at the
      95% confidence level (MDC95) were computed for the 30-RST. Relationships between
      30-RST and dynamic measures were moderate to very good (r = -0.35-0.73, p <
      0.05); however, relationships between 30-RST and static balance were weak (r =
      0.04-0.19, p > 0.05). The ICC2,1 was 0.85 for 30-RST indicating excellent test
      retest reliability. SEM expressed as a percent of mean 30-RST was 8.2%,
      indicating low measurement error. The MDC95 was 9.4 s, and MDC95 expressed as a
      percent of mean 30-RST was moderately low at 22.6%. The 30-RST is a valid measure
      of dynamic balance and mobility with excellent relative and absolute reliability,
      and may be a useful measure in geriatric clinical settings and studies
      investigating balance in healthy community-dwelling older adults.

PMID- 26200438
TI  - Some Important Deficiencies in the Development, Validation, and Reporting of a
      Prediction Model.

PMID- 26200439
TI  - Multiscale Biofabrication of Articular Cartilage: Bioinspired and Biomimetic
      Approaches.
AB  - Articular cartilage is the load-bearing tissue found inside all articulating
      joints of the body. It vastly reduces friction and allows for smooth gliding
      between contacting surfaces. The structure of articular cartilage matrix and
      cellular composition is zonal and is important for its mechanical properties.
      When cartilage becomes injured through trauma or disease, it has poor intrinsic
      healing capabilities. The spectrum of cartilage injury ranges from isolated areas
      of the joint to diffuse breakdown and the clinical appearance of osteoarthritis.
      Current clinical treatment options remain limited in their ability to restore
      cartilage to its normal functional state. This review focuses on the evolution of
      biomaterial scaffolds that have been used for functional cartilage tissue
      engineering. In particular, we highlight recent developments in multiscale
      biofabrication approaches attempting to recapitulate the complex 3D matrix of
      native articular cartilage tissue. Additionally, we focus on the application of
      these methods to engineering each zone of cartilage and engineering full
      thickness osteochondral tissues for improved clinical implantation. These methods
      have shown the potential to control individual cell-to-scaffold interactions and
      drive progenitor cell differentiation into a chondrocyte lineage. The use of
      these bioinspired nanoengineered scaffolds hold promise for recreation of
      structure and function on the whole tissue level and may represent exciting new
      developments for future clinical applications for cartilage injury and
      restoration. 

PMID- 26200440
TI  - Kawasaki disease with pulmonary nodules and coronary artery involvement: a report
      of two cases and a review of the literature.

PMID- 26200443
TI  - Highly Sensitive Detection of Surface and Intercalated Impurities in Graphene by
      LEIS.
AB  - Low-energy ion scattering (LEIS) is known for its extreme surface sensitivity, as
      it yields a quantitative analysis of the outermost surface as well as highly
      resolved in-depth information for ultrathin surface layers. Hence, it could have
      been generally considered to be a suitable technique for the analysis of graphene
      samples. However, due to the low scattering cross section for light elements such
      as carbon, LEIS has not become a common technique for the characterization of
      graphene. In the present study we use a high-sensitivity LEIS instrument with
      parallel energy analysis for the characterization of CVD graphene transferred to
      thermal silica/silicon substrates. Thanks to its high sensitivity and the
      exceptional depth resolution typical of LEIS, the graphene layer closure was
      verified, and different kinds of contaminants were detected, quantified, and
      localized within the graphene structure. Utilizing the extraordinarily strong
      neutralization of helium by carbon atoms in graphene, LEIS experiments performed
      at several primary ion energies permit us to distinguish carbon in graphene from
      that in nongraphitic forms (e.g., the remains of a resist). Furthermore, metal
      impurities such as Fe, Sn, and Na located at the graphene-silica interface
      (intercalated) are detected, and the coverages of Fe and Sn are determined.
      Hence, high-resolution LEIS is capable of both checking the purity of graphene
      surfaces and detecting impurities incorporated into graphene layers or their
      interfaces. Thus, it is a suitable method for monitoring the quality of the whole
      fabrication process of graphene, including its transfer on various substrates. 

PMID- 26200444
TI  - Efficacy of atorvastatin on hippocampal neuronal damage caused by chronic
      intermittent hypoxia: Involving TLR4 and its downstream signaling pathway.
AB  - Hippocampal neuronal damage is critical for the initiation and progression of
      neurocognitive impairment accompanied obstructive sleep apnea syndrome (OSAS).
      Toll-like receptor 4 (TLR4) plays an important role in the development of several
      hippocampus-related neural disorders. Atorvastatin was reported beneficially
      regulates TLR4. Here, we examined the effects of atorvastatin on hippocampal
      injury caused by chronic intermittent hypoxia (CIH), the most characteristic
      pathophysiological change of OSAS. Mice were exposed to intermittent hypoxia with
      or without atorvastatin for 4 weeks. Cell damage, the expressions of TLR4 and its
      two downstream factors myeloid differentiation factor 88 (MYD88) and TIR-domain
      containing adapter-inducing interferon-beta (TRIF), inflammatory agents (tumor
      necrosis factor alpha and interleukin 1beta), and the oxidative stress
      (superoxide dismutase and malondialdehyde) were determined. Atorvastatin
      decreased the neural injury and the elevation of TLR4, MyD88, TRIF, pro
      inflammatory cytokines and oxidative stress caused by CIH. Our study suggests
      that atorvastatin may attenuate CIH induced hippocampal neuronal damage partially
      via TLR4 and its downstream signaling pathway. 

PMID- 26200445
TI  - Pain in Community-Dwelling Older Adults with Dementia: Results from the National
      Health and Aging Trends Study.
AB  - OBJECTIVES: To report prevalence, correlates, and medication management of pain
      in community-dwelling older adults with dementia. DESIGN: Cross-sectional.
      SETTING: In-person interviews with self- or proxy respondents living in private
      residences or non-nursing home residential care settings. PARTICIPANTS:
      Nationally representative sample of community-dwelling Medicare beneficiaries
      aged 65 and older enrolled in the National Health and Aging Trends Study 2011
      wave. MEASUREMENTS: Dementia status was determined using a modified previously
      validated algorithm. Participants were asked whether they had had bothersome and
      activity-limiting pain over the past month. A multivariable Poisson regression
      model was used to determine the relationship between bothersome pain and
      sociodemographic and clinical characteristics. RESULTS: Of the 7,609 participants
      with complete data on cognitive function, 802 had dementia (67.2% aged >=80,
      65.0% female, 67.9% white, 49.7% proxy response, 32.0% lived alone, 18.8% lived
      in residential care); 670 (63.5%) participants with dementia experienced
      bothersome pain, and 347 (43.3%) had pain that limited activities. These rates
      were significantly higher than in a propensity score-matched cohort without
      dementia (54.5% bothersome pain, P < .001, 27.2% pain that limited activity, P <
      .001). Proxies reported slightly higher rates of pain than self-respondents, but
      differences were statistically significant only for activity-limiting pain (46.6%
      proxy vs 40.1% self, P = .03). Correlates of bothersome pain included arthritis,
      heart and lung disease, less than high school education, activity of daily living
      disability, depressive and anxiety symptoms, and low energy. Of those reporting
      pain, 30.3% stated that they rarely or never took any medications for pain.
      CONCLUSION: Community-living older adults with dementia are at high risk of
      having pain. Creative interventions and programs are needed to manage pain
      adequately in this vulnerable population.

PMID- 26200446
TI  - Design, Synthesis, and Evaluation of Polyamine Deacetylase Inhibitors, and High
      Resolution Crystal Structures of Their Complexes with Acetylpolyamine
      Amidohydrolase.
AB  - Polyamines are essential aliphatic polycations that bind to nucleic acids and
      accordingly are involved in a variety of cellular processes. Polyamine function
      can be regulated by acetylation and deacetylation, just as histone function can
      be regulated by lysine acetylation and deacetylation. Acetylpolyamine
      amidohydrolase (APAH) from Mycoplana ramosa is a zinc-dependent polyamine
      deacetylase that shares approximately 20% amino acid sequence identity with human
      histone deacetylases. We now report the X-ray crystal structures of APAH
      inhibitor complexes in a new and superior crystal form that diffracts to very
      high resolution (1.1-1.4 A). Inhibitors include previously synthesized analogues
      of N(8)-acetylspermidine bearing trifluoromethylketone, thiol, and hydroxamate
      zinc-binding groups [Decroos, C., Bowman, C. M., and Christianson, D. W. (2013)
      Bioorg. Med. Chem. 21, 4530], and newly synthesized hydroxamate analogues of
      shorter, monoacetylated diamines, the most potent of which is the hydroxamate
      analogue of N-acetylcadaverine (IC50 = 68 nM). The high-resolution crystal
      structures of APAH-inhibitor complexes provide key inferences about the
      inhibition and catalytic mechanism of zinc-dependent deacetylases. For example,
      the trifluoromethylketone analogue of N(8)-acetylspermidine binds as a
      tetrahedral gem-diol that mimics the tetrahedral intermediate and its flanking
      transition states in catalysis. Surprisingly, this compound is also a potent
      inhibitor of human histone deacetylase 8 with an IC50 of 260 nM. Crystal
      structures of APAH-inhibitor complexes are determined at the highest resolution
      of any currently existing zinc deacetylase structure and thus represent the most
      accurate reference points for understanding structure-mechanism and structure
      inhibition relationships in this critically important enzyme family. 

PMID- 26200448
TI  - Assessing the impact of upper limb disability following stroke: a qualitative
      enquiry using internet-based personal accounts of stroke survivors.
AB  - PURPOSE: Upper limb disability following stroke may have multiple effects on the
      individual. Existing assessment instruments tend to focus on impairment and
      function and may miss other changes that are personally important. This study
      aimed to identify personally significant impacts of upper limb disability
      following stroke. METHODS: Accounts by stroke survivors, in the form of web-based
      diaries (blogs) and stories, were sought using a blog search engine and in stroke
      related web-sites. Thematic analysis using the World Health Organisation's
      International Classification of Functioning Disability and Health (ICF) was used
      to identify personal impacts of upper limb disability following stroke. RESULTS:
      Ninety-nine sources from at least four countries were analysed. Many impacts were
      classifiable using the ICF, but a number of additional themes emerged, including
      emotional, cognitive and behavioural changes. Blogs and other web-based accounts
      were easily accessible and rich sources of data, although using them raised
      several methodological issues, including potential sample bias. CONCLUSIONS: A
      range of impacts was identified, some of which (such as use of information
      technology and alienation from the upper limb) are not addressed in current
      assessment instruments. They should be considered in post-stroke assessments.
      Blogs may help in the development of more comprehensive assessments. IMPLICATIONS
      FOR REHABILITATION: A comprehensive assessment of the upper limb following stroke
      should include the impact of upper limb problems on social participation, as well
      as associated emotional, cognitive and behavioural changes. Using personalised
      assessment instruments alongside standardised measures may help ensure that these
      broader domains are considered in discussions between clinicians and patients.
      Rehabilitation researchers should investigate whether and how these domains could
      be addressed and operationalised in standard upper limb assessment instruments.

PMID- 26200449
TI  - Choral singing therapy following stroke or Parkinson's disease: an exploration of
      participants' experiences.
AB  - PURPOSE: People with stroke or Parkinson's disease (PD) live with reduced mood,
      social participation and quality of life (QOL). Communication difficulties affect
      90% of people with PD (dysarthria) and over 33% of people with stroke (aphasia).
      These consequences are disabling in many ways. However, as singing is typically
      still possible, its therapeutic use is of increasing interest. This article
      explores the experiences of and factors influencing participation in choral
      singing therapy (CST) by people with stroke or PD and their significant others.
      METHOD: Participants (eight people with stroke, six with PD) were recruited from
      a community music therapy choir running CST. Significant others (seven for
      stroke, two for PD) were also recruited. Supported communication methods were
      used as needed to undertake semi-structured interviews (total N = 23). RESULTS:
      Thematic analysis indicated participants had many unmet needs associated with
      their condition, which motivated them to explore self-management options. CST
      participation was described as an enjoyable social activity, and participation
      was perceived as improving mood, language, breathing and voice. CONCLUSIONS:
      Choral singing was perceived by people with stroke and PD to help them self
      manage some of the consequences of their condition, including social isolation,
      low mood and communication difficulties. IMPLICATIONS FOR REHABILITATION: Choral
      singing therapy (CST) is sought out by people with stroke and PD to help self
      manage symptoms of their condition. Participation is perceived as an enjoyable
      activity which improves mood, voice and language symptoms. CST may enable access
      to specialist music therapy and speech language therapy protocols within
      community frameworks.

PMID- 26200450
TI  - Negative Thyroid Transcription Factor 1 Expression Defines an Unfavorable
      Subgroup of Lung Adenocarcinomas.
AB  - INTRODUCTION: Thyroid transcription factor 1 (TTF1) is a master regulator of
      pulmonary differentiation that is downregulated in a subset of lung
      adenocarcinoma, of which the clinicopathologic characteristics were not fully
      clarified. METHODS: One thousand forty-two lung adenocarcinoma patients who
      underwent surgery were investigated for clinic characteristics, histologic
      subtyping, and spectrum of well-identified driver mutations. TTF1 expression was
      correlated with these clinicopathologic factors and survival. RESULTS: Compared
      with TTF1 positive (TTF1+) patients, the 133 negative individuals (12.8%, TTF1-)
      were more likely to be male (p = 0.006) and heavy smokers (p = 0.002) who had
      larger tumor size (p < 0.001) and more advanced disease stage (p < 0.001). TTF1-
      presented more in solid and invasive mucinous-predominant carcinomas (both p <
      0.001), whereas TTF1+ was identified in 100% patients with adenocarcinoma in
      situ, minimally invasive and lepidic-predominant adenocarcinomas. The TTF1-
      tumors harbored the known driver mutations in significantly low frequency
      compared with TTF1+ adenocarcinomas (57.8% versus 78.1%, p < 0.001), especially
      in epidermal growth factor receptor (EGFR) mutations (37.6% versus 60.7%, p <
      0.001). There was no significant difference in recurrence-free survival between
      the TTF1- and TTF1+ patients, either for the whole cohort or stratified by
      pathologic stage, or among the driver mutation-defined subsets. However,
      recurrence of multiple metastases was more likely to occur in patients with TTF1-
      adenocarcinomas (88.1% versus 32.4%, p < 0.001). Multivariate analysis revealed
      that TTF1- independently predicted both poor postrecurrence survival (hazard
      ratio = 1.664; 95% confidence interval , 1.097-2.524; p = 0.017) and unfavorable
      overall survival (hazard ratio = 1.553; 95% confidence interval , 1.013-2.381; p
      = 0.043). CONCLUSIONS: TTF1- correlated with solid and invasive mucinous subtypes
      of lung adenocarcinoma and lower frequency of EGFR mutations. It defines a
      subgroup of lung adenocarcinomas with unfavorable outcomes.

PMID- 26200451
TI  - Early Detection of Lung Cancer with Meso Tetra (4-Carboxyphenyl) Porphyrin
      Labeled Sputum.
AB  - INTRODUCTION: Early detection of lung cancer in high-risk individuals reduces
      mortality. Low-dose spiral computed tomography (LDCT) is the current standard but
      suffers from an exceedingly high false-positive rate (>96%) leading to
      unnecessary and potentially dangerous procedures. We, therefore, set out to
      develop a simple, noninvasive, and quantitative assay to detect lung cancer.
      METHODS: This proof-of-concept study evaluated the sensitivity/specificity of the
      CyPath Early Lung Cancer Detection Assay to correctly classify LDCT-confirmed
      cohorts of high-risk control (n = 102) and cancer (n = 26) subjects. Fluorescence
      intensity parameters of red fluorescent cells (RFCs) from tetra (4-carboxyphenyl)
      porphyrin (TCPP)-labeled lung sputum samples and subjects' baseline
      characteristics were assessed for their predictive power by multivariable
      logistic regression. A receiver operating characteristic curve was constructed to
      evaluate the sensitivity/specificity of the CyPath assay. RESULTS: RFCs were
      detectable in cancer subjects more often than in high-risk ones (p = 0.015), and
      their characteristics differed between cohorts. Two independent predictors of
      cancer were the mean of RFC average fluorescence intensity/area per subject (p <
      0.001) and years smoked (p = 0.003). The CyPath-based classifier had an overall
      accuracy of 81% in the test population; false-positive rate of 40% and negative
      predictive value of 83%. CONCLUSIONS: The tetra (4-carboxyphenyl) porphyrin 
      based CyPath assay correctly classified study participants into cancer or high
      risk cohorts with considerable accuracy. Optimizing sputum collection, sample
      reading, and refining the classifier should improve sensitivity and specificity.
      The CyPath assay thus has the potential to complement LDCT screening or serve as
      a stand-alone approach for early lung cancer detection.

PMID- 26200452
TI  - Racial Disparities in Health-Related Quality of Life After Lung Cancer Surgery:
      Findings From the Cancer Care Outcomes Research and Surveillance Consortium.
AB  - INTRODUCTION: This study investigated racial disparities in postsurgical health
      related quality of life (HRQOL) among patients with non-small-cell lung cancer
      (NSCLC). METHODS: Data were collected by the Cancer Care Outcomes Research and
      Surveillance Consortium. Inclusion criteria were greater than or equal to 21
      years of age, NSCLC, and receipt of surgery. HRQOL data were available from
      patients' surveys, and complete medical record abstraction was performed to
      obtain clinical data. HRQOL was assessed by the physical/mental component summary
      scores (PCS/MCS) of the 12-item Short-Form Health Survey at two time points. Mean
      time between surgery and the initial assessment (time 1) after surgery was 4.1
      (SD 2.2) months and between surgery and second assessment (time 2) was 12.7 (SD
      3.8) months. Multivariable linear regression models were used to examine
      associations between race and HRQOL. RESULTS: Of 650 patients, 80.5% were White,
      8.8% Black, and 10.7% other races. At second assessment, Blacks reported lower
      MCS than Whites (47.4 versus 52.6, p = 0.002). In multivariable analysis, Blacks
      had lower MCS compared with Whites. No difference was found between Whites and
      Blacks on PCS. Those with less than high school education reported lower MCSs.
      Older age and receipt of adjuvant chemotherapy after surgery were associated with
      gain in MCS. Male, less than college education, and comorbidities were associated
      with impaired PCS. Older age was associated with improved PCS. CONCLUSION: Racial
      disparities exist in postoperative mental HRQOL. Results highlight the need for
      interventions after lung cancer surgery to improve mental health in Black and
      younger patients.

PMID- 26200453
TI  - Risk Stratification Model for Resected Squamous-Cell Lung Cancer Patients
      According to Clinical and Pathological Factors.
AB  - INTRODUCTION: The aim of this analysis (AIRC-MFAG project no. 14282) was to
      define a risk classification for resected squamous-cell lung cancer based on the
      combination of clinicopathological predictors to provide a practical tool to
      evaluate patients' prognosis. METHODS: Clinicopathological data were
      retrospectively correlated to disease-free/cancer-specific/overall survival
      (DFS/CSS/OS) using a Cox model. Individual patient probability was estimated by
      logistic equation. A continuous score to identify risk classes was derived
      according to model ratios and dichotomized according to prognosis with receiver
      operating characteristic analysis. RESULTS: Data from 573 patients from five
      institutions were gathered. Four hundred ninety-four patients were evaluable for
      clinical analysis (median age: 68 years; male/female: 403/91; T-descriptor
      according to TNM 7th edition 1-2/3-4: 330/164; nodes 0/>0: 339/155; stages I and
      II/III and IV: 357/137). At multivariate analysis, age, T-descriptor according to
      TNM 7th edition, nodes, and grading were independent predictors for DFS and OS;
      the same factors, except age and grading, predicted CSS. Multivariate model
      predict individual patient probability with high prognostic accuracy (0.67 for
      DFS). On the basis of receiver operating characteristic-derived cutoff, a two
      class model significantly differentiated low-risk and high-risk patients for 3
      year DFS (64.6% and 32.4%, p < 0.0001), CSS (84.4% and 44.5%, p < 0.0001), and OS
      (77.3% and 38.8%, p < 0.0001). A three-class model separated low-risk,
      intermediate-risk, and high-risk patients for 3-year DFS (64.6%, 39.8%, and
      21.8%, p < 0.0001), CSS (84.4%, 55.4%, and 30.9%, p< 0.0001), and OS (77.3%,
      47.9%, and 27.2%, p < 0.0001). CONCLUSIONS: A risk stratification model including
      often adopted clinicopathological parameters accurately separates resected
      squamous-cell lung cancer patients into different risk classes. The project is
      currently ongoing to integrate the clinicopathological model with investigational
      molecular predictors.

PMID- 26200454
TI  - Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the
      European EURAF Cohort.
AB  - INTRODUCTION: Approximately 2% of lung adenocarcinomas have BRAF (v-Raf murine
      sarcoma viral oncogene homolog B) mutations, including V600E and other types.
      Vemurafenib, dabrafenib, and sorafenib as BRAF inhibitors are currently tested in
      clinical trials, but access for patients is limited. The aim of this study was to
      document the clinical course of patients treated outside of clinical trials.
      METHODS: We conducted a retrospective multicenter cohort study in Europe of
      patients with advanced BRAF-mutant lung cancer treated with known BRAF
      inhibitors. Data were anonymized and centrally assessed for age, gender, smoking,
      histology, stage, local molecular diagnostic results, systemic therapies, and
      survival. Best response was assessed locally by RECIST1.1. RESULTS: We documented
      35 patients treated in 17 centers with vemurafenib, dabrafenib, or sorafenib.
      Median age was 63 years (range 42-85); gender was balanced; 14 (40%) were never
      smokers; all (100%) had adenocarcinoma; 29 (83%) had V600E; 6 (17%) had other
      mutations; one of them had a concomitant KRAS mutation. Thirty (86%) patients had
      chemotherapy in the first line. Overall survival with first-line therapy was 25.3
      months for V600E and 11.8 months for non-V600E. Thirty-one patients received one
      BRAF inhibitor, and four received a second inhibitor. Overall response rate with
      BRAF therapy was 53%, and disease control rate was 85%. Median progression-free
      survival with BRAF therapy was 5.0 months, and overall survival was 10.8 months.
      CONCLUSIONS: These results confirm the activity of targeted therapy in patients
      with BRAF-mutant lung adenocarcinoma. Further trials are warranted to study
      combination therapies and drug resistance mechanisms.

PMID- 26200455
TI  - Genetic Evidence Supports the Multiethnic Character of Teopancazco, a
      Neighborhood Center of Teotihuacan, Mexico (AD 200-600).
AB  - Multiethnicity in Teopancazco, Teotihuacan, is supported by foreign individuals
      found in the neighborhood center as well as by the diversity observed in funerary
      rituals at the site. Studies of both stable and strontium isotopes as well as
      paleodietary analysis, suggest that the population of Teopancazco was composed by
      three population groups: people from Teotihuacan, people from nearby sites
      (Tlaxcala-Hidalgo-Puebla), and people from afar, including the coastal plains. In
      an attempt to understand the genetic dynamics in Teopancazco we conducted an
      ancient DNA (aDNA) analysis based on mtDNA. Our results show that the level of
      genetic diversity is consistent with the multiethnicity phenomenon at the
      neighborhood center. Levels of genetic diversity at different time periods of
      Teopancazco's history show that multiethnicity was evident since the beginning
      and lasted until the collapse of the neighborhood center. However, a PCA and a
      Neighbor-Joining tree suggested the presence of a genetically differentiated
      group (buried at the Transitional phase) compared to the population from the
      initial phase (Tlamimilolpa) as well as the population from the final phase
      (Xolalpan) of the history of Teopancazco. Genetic studies showed no differences
      in genetic diversity between males and females in the adult population of
      Teopancazco, this data along with ample archaeological evidence, suggest a
      neolocal post-marital pattern of residence in Teopancazco. Nevertheless, genetic
      analyses on the infant population showed that the males are significantly more
      heterogeneous than the females suggesting a possible differential role in
      cultural practices by sex in the infant sector. Regarding interpopulation
      analysis, we found similar indices of genetic diversity between Teopancazco and
      heterogeneous native groups, which support the multiethnic character of
      Teopancazco. Finally, our data showed a close genetic relationship between
      Teopancazco and populations from the "Teotihuacan corridor" and from Oaxaca and
      the Maya region, in agreement with previous archaeological evidence. 

PMID- 26200456
TI  - Reproductive Failure in UK Harbour Porpoises Phocoena phocoena: Legacy of
      Pollutant Exposure?
AB  - Reproductive failure in mammals due to exposure to polychlorinated biphenyls
      (PCBs) can occur either through endocrine disrupting effects or via
      immunosuppression and increased disease risk. To investigate further, full
      necropsies and determination of summed 25 polychlorinated biphenyls congeners
      (?PCBs lipid weight) in blubber were undertaken on 329 UK-stranded female harbour
      porpoises (1990-2012). In sexually mature females, 25/127 (19.7%) showed direct
      evidence of reproductive failure (foetal death, aborting, dystocia or
      stillbirth). A further 21/127 (16.5%) had infections of the reproductive tract or
      tumours of reproductive tract tissues that could contribute to reproductive
      failure. Resting mature females (non-lactating or non-pregnant) had significantly
      higher mean ?PCBs (18.5 mg/kg) than both lactating (7.5 mg/kg) and pregnant
      females (6 mg/kg), though not significantly different to sexually immature
      females (14.0 mg/kg). Using multinomial logistic regression models SigmaPCBs was
      found to be a significant predictor of mature female reproductive status,
      adjusting for the effects of confounding variables. Resting females were more
      likely to have a higher PCB burden. Health status (proxied by "trauma" or
      "infectious disease" causes of death) was also a significant predictor, with
      lactating females (i.e. who successfully reproduced) more likely to be in good
      health status compared to other individuals. Based on contaminant profiles (>11
      mg/kg lipid), at least 29/60 (48%) of resting females had not offloaded their
      pollutant burden via gestation and primarily lactation. Where data were
      available, these non-offloading females were previously gravid, which suggests
      foetal or newborn mortality. Furthermore, a lower pregnancy rate of 50% was
      estimated for "healthy" females that died of traumatic causes of death, compared
      to other populations. Whether or not PCBs are part of an underlying mechanism, we
      used individual PCB burdens to show further evidence of reproductive failure in
      the North-east Atlantic harbour porpoise population, results that should inform
      conservation management. 

PMID- 26200458
TI  - Factors Associated with Awareness, Attitudes and Practices Regarding Common Eye
      Diseases in the General Population in a Rural District in Bangladesh: The
      Bangladesh Population-based Diabetes and Eye Study (BPDES).
AB  - BACKGROUND: To assess the awareness, attitudes, and practices associated with
      common eye diseases and eye care utilization in a rural district of Bangladesh.
      METHODS: Data were collected using a multilevel cluster random sampling technique
      from 3104 adults aged >=30 years from the Banshgram union with a questionnaire
      assessing the awareness, attitudes and practice about diabetes and common eye
      diseases, educational attainment, socio-economic status, and medical history.
      RESULTS: Participants were aged between 30 and 89 years with a mean (SD) age of
      51 (12) years and 65% were female. The majority of participants had heard of
      cataracts (90%), trachoma (86%) and Pterygium (84%), yet only 4% had heard of
      diabetic retinopathy (DR), 7% of glaucoma and 8% of Age-related macular
      degeneration (AMD). However, 58% of participants did not know vision loss could
      be prevented. Factors associated with lower awareness regarding common eye
      diseases were increasing age, lack of formal schooling, and lower socio-economic
      status. A lower proportion (57%) of people with no schooling compared to those
      who had attained at least secondary school certificate education (72%) reported
      that they knew that vision loss could be prevented (p<0.001). Overall 51% of
      people had heard of at least six (67%) out of nine items relating to awareness of
      common eye diseases. This included 41% of participants aged 65 years or older
      compared to 61% of those aged 30-35 years (p<0.001). Only 4% had an eye check at
      least once a year and higher education and better SES were associated with higher
      frequency of eye checks. CONCLUSIONS: In rural Bangladesh awareness of cataract,
      trachoma and pterygium was good but limited in relation to the potentially
      blinding conditions of glaucoma, DR, and AMD. The results show a large gap
      between public awareness and treatment practices about common eye diseases.
      Public health promotion should be designed to address these knowledge gaps.

PMID- 26200457
TI  - Smoking, Smoking Cessation, and the Risk of Type 2 Diabetes among Japanese
      Adults: Japan Epidemiology Collaboration on Occupational Health Study.
AB  - AIMS: To examine the association of smoking status, smoking intensity, and
      smoking cessation with the risk of type 2 diabetes (T2D) using a large database.
      METHODS: The present study included 53,930 Japanese employees, aged 15 to 83
      years, who received health check-up and did not have diabetes at baseline.
      Diabetes was defined as fasting plasma glucose >=126 mg/dl, random plasma glucose
      >=200 mg/dl, HbA1c >=6.5% (>=48 mmol/mol), or receiving medication for diabetes.
      Cox proportional-hazards regression models were used to investigate the
      association between smoking and the risk of diabetes. RESULTS: During 3.9 years
      of median follow-up, 2,441 (4.5%) individuals developed T2D. The multivariable
      adjusted hazard ratios (95% CI) for diabetes were 1 (reference), 1.16 (1.04 to
      1.30) and 1.34 (1.22 to 1.48) for never smokers, former smokers, and current
      smokers, respectively. Diabetes risk increased with increasing numbers of
      cigarette consumption among current smokers (P for trend <0.001). Although the
      relative risk of diabetes was greater among subjects with lower BMIs (< 23
      kg/m2), attributable risk was greater in subjects with higher BMIs (>= 23 kg/m2).
      Compared with individuals who had never smoked, former smokers who quit less than
      5 years, 5 to 9 years, and 10 years or more exhibited hazards ratios for diabetes
      of 1.36 (1.14 to 1.62), 1.23 (1.01 to 1.51), and 1.02 (0.85 to 1.23),
      respectively. CONCLUSIONS: Results suggest that cigarette smoking is associated
      with an increased risk of T2D, which may decrease to the level of a never smoker
      after 10 years of smoking cessation.

PMID- 26200459
TI  - Molecular Phylogenetic Analysis of Ballistoconidium-Forming Yeasts in
      Trichosporonales (Tremellomycetes): A Proposal for Takashimella gen. nov. and
      Cryptotrichosporon tibetense sp. nov.
AB  - Bullera species in the Trichosporonales (Tremellomycetes, Agaricomycotina) are
      phylogenetically distinct from Bullera alba (teleomorph: Bulleromyces albus), the
      type species of Bullera that belongs to Tremellales. In the present study, the
      three Bullera species, namely Bullera formosensis, Bullera koratensis and Bullera
      lagerstroemiae, and Cryptococcus tepidarius belonging to the Trichosporonales are
      transferred into a new genus Takashimella gen. nov. (MycoBank No. MB 810672)
      based on sequence analysis of the small subunit (SSU) rRNA gene, the D1/D2
      domains of large subunit (LSU) rRNA gene and the ITS+5.8S rRNA gene sequences. In
      addition, the genus Cryptotrichosporon is emended to accommodate a novel
      ballistoconidium-forming species of the Trichosporonales, which is named as
      Cryptotrichosporon tibetense (type strain CGMCC 2.02614T = CBS 10455T). The
      MycoBank number of this new species is MB 810688. 

PMID- 26200460
TI  - From synthesis to function via iterative assembly of N-methyliminodiacetic acid
      boronate building blocks.
AB  - The study and optimization of small molecule function is often impeded by the
      time-intensive and specialist-dependent process that is typically used to make
      such compounds. In contrast, general and automated platforms have been developed
      for making peptides, oligonucleotides, and increasingly oligosaccharides, where
      synthesis is simplified to iterative applications of the same reactions. Inspired
      by the way natural products are biosynthesized via the iterative assembly of a
      defined set of building blocks, we developed a platform for small molecule
      synthesis involving the iterative coupling of haloboronic acids protected as the
      corresponding N-methyliminodiacetic acid (MIDA) boronates. Here we summarize our
      efforts thus far to develop this platform into a generalized and automated
      approach for small molecule synthesis. We and others have employed this approach
      to access many polyene-based compounds, including the polyene motifs found in
      >75% of all polyene natural products. This platform further allowed us to
      derivatize amphotericin B, the powerful and resistance-evasive but also highly
      toxic last line of defense in treating systemic fungal infections, and thereby
      understand its mechanism of action. This synthesis-enabled mechanistic
      understanding has led us to develop less toxic derivatives currently under
      evaluation as improved antifungal agents. To access more Csp(3)-containing small
      molecules, we gained a stereocontrolled entry into chiral, non-racemic alpha
      boryl aldehydes through the discovery of a chiral derivative of MIDA. These alpha
      boryl aldehydes are versatile intermediates for the synthesis of many Csp(3)
      boronate building blocks that are otherwise difficult to access. In addition, we
      demonstrated the utility of these types of building blocks in accessing
      pharmaceutically relevant targets via an iterative Csp(3) cross-coupling cycle.
      We have further expanded the scope of the platform to include stereochemically
      complex macrocyclic and polycyclic molecules using a linear-to-cyclized strategy,
      in which Csp(3) boronate building blocks are iteratively assembled into linear
      precursors that are then cyclized into the cyclic frameworks found in many
      natural products and natural product-like structures. Enabled by the
      serendipitous discovery of a catch-and-release protocol for generally purifying
      MIDA boronate intermediates, the platform has been automated. The synthesis of 14
      distinct classes of small molecules, including pharmaceuticals, materials
      components, and polycyclic natural products, has been achieved using this new
      synthesis machine. It is anticipated that the scope of small molecules accessible
      by this platform will continue to expand via further developments in building
      block synthesis, Csp(3) cross-coupling methodologies, and cyclization strategies.
      Achieving these goals will enable the more generalized synthesis of small
      molecules and thereby help shift the rate-limiting step in small molecule science
      from synthesis to function. 

PMID- 26200461
TI  - Trends in Stranding and By-Catch Rates of Gray and Harbor Seals along the
      Northeastern Coast of the United States: Evidence of Divergence in the Abundance
      of Two Sympatric Phocid Species?
AB  - Harbor seals and gray seals are sympatric phocid pinnipeds found in coastal
      waters of the temperate and sub-Arctic North Atlantic. In the Northwest Atlantic,
      both species were depleted through a combination of subsistence hunts and
      government supported bounties, and are now re-occupying substantial portions of
      their original ranges. While both species appear to have recovered during the
      past 2 decades, our understanding of their population dynamics in US waters is
      incomplete. Here we describe trends in stranding and bycatch rates of harbor and
      gray seals in the North East United States (NEUS) over the past 16 years through
      an exploratory curve-fitting exercise and structural break-point analysis.
      Variability in gray seal strandings in Southern New England and bycatch in the
      Northeast Sink Gillnet Fishery were best described by fitting positive
      exponential and linear models, and exhibited rates of increase as high as 22%. In
      contrast, neither linear nor exponential models fit the oscillation of harbor
      seal strandings and bycatch over the study period. However, a breakpoint Chow
      test revealed that harbor seal strandings in the Cape Cod, Massachusetts region
      and harbor seal bycatch in the Northeast Sink Gillnet Fishery increased in the
      1990s and then started declining in the early to mid-2000s. Our analysis
      indicates that ongoing variation in natural and anthropogenic mortality rates of
      harbor and gray seals in the NEUS is not synchronous, and likely represents
      diverging trends in abundance of these species as they assume new roles in the
      marine ecosystems of the region. 

PMID- 26200462
TI  - HDAC8, A Potential Therapeutic Target for the Treatment of Malignant Peripheral
      Nerve Sheath Tumors (MPNST).
AB  - INTRODUCTION: HDAC isoform-specific inhibitors may improve the therapeutic window
      while limiting toxicities. Developing inhibitors against class I isoforms poses
      difficulties as they share high homology among their catalytic sites; however,
      HDAC8 is structurally unique compared to other class I isoforms. HDAC8 inhibitors
      are novel compounds and have affinity for class I HDAC isoforms demonstrating
      anti-cancer effects; little is known about their activity in malignant peripheral
      nerve sheath tumors (MPNST). Recently, we demonstrated anti-MPNST efficacy of
      HDAC8i in human and murine-derived MPNST pre-clinical models; we now seek to
      consider the potential therapeutic inhibition of HDAC8 in MPNST. METHODS: Four
      Human MPNST cell lines, a murine-derived MPNST cell line, and two HDAC8
      inhibitors (PCI-34051, PCI-48012; Pharmacyclics, Inc. Sunnyvale, CA) were
      studied. Proliferation was determined using MTS and clonogenic assays. Effects on
      cell cycle were determined via PI FACS analysis; effects on apoptosis were
      determined using Annexin V-PI FACS analysis and cleaved caspase 3 expression. In
      vivo growth effects of HDAC8i were evaluated using MPNST xenograft models. 2D gel
      electrophoresis and mass spectrometry were used to identify potential HDAC8
      deacetylation substrates. RESULTS: HDAC8i induced cell growth inhibition and
      marked S-phase cell cycle arrest in human and murine-derived MPNST cells.
      Relative to control, HDAC8i induced apoptosis in both human and murine-derived
      MPNST cells. HDAC8i exhibited significant effects on MPNST xenograft growth
      (p=0.001) and tumor weight (p=0.02). Four potential HDAC8 substrate targets were
      identified using a proteomic approach: PARK7, HMGB1, PGAM1, PRDX6. CONCLUSIONS:
      MPNST is an aggressive sarcoma that is notoriously therapy-resistant, hence the
      urgent need for improved anti-MPNST therapies. HDAC8 inhibition may be useful for
      MPNST by improving efficacy while limiting toxicities as compared to pan-HDACis.

PMID- 26200464
TI  - Nanomechanics of Cells and Biomaterials Studied by Atomic Force Microscopy.
AB  - The behavior and mechanical properties of cells are strongly dependent on the
      biochemical and biomechanical properties of their microenvironment. Thus,
      understanding the mechanical properties of cells, extracellular matrices, and
      biomaterials is key to understanding cell function and to develop new materials
      with tailored mechanical properties for tissue engineering and regenerative
      medicine applications. Atomic force microscopy (AFM) has emerged as an
      indispensable technique for measuring the mechanical properties of biomaterials
      and cells with high spatial resolution and force sensitivity within
      physiologically relevant environments and timescales in the kPa to GPa elastic
      modulus range. The growing interest in this field of bionanomechanics has been
      accompanied by an expanding array of models to describe the complexity of
      indentation of hierarchical biological samples. Furthermore, the integration of
      AFM with optical microscopy techniques has further opened the door to a wide
      range of mechanotransduction studies. In recent years, new multidimensional and
      multiharmonic AFM approaches for mapping mechanical properties have been
      developed, which allow the rapid determination of, for example, cell elasticity.
      This Progress Report provides an introduction and practical guide to making AFM
      based nanomechanical measurements of cells and surfaces for tissue engineering
      applications. 

PMID- 26200465
TI  - A Randomized, Prospective, Double-Blinded Study of Physostigmine to Prevent
      Sedation-Induced Ventilatory Arrhythmias.
AB  - BACKGROUND: Physostigmine, a centrally acting acetylcholinesterase inhibitor, is
      most commonly used by anesthesiologists in the postanesthetic setting to reverse
      confusion caused by central anticholinergic medication effects. It has also been
      proposed as a treatment for sleep-disordered breathing. We investigated whether
      physostigmine was effective in decreasing the frequency of ventilatory
      arrhythmias produced during moderate sedation with midazolam and remifentanil
      during the conditions of breathing room air or 2 L/min nasal O2. METHODS: Ten
      healthy male volunteers participated in this randomized, double-blind control
      trial of physostigmine (0.24 ug.kg.min) versus placebo. Moderate sedation was
      achieved with infusions of midazolam and remifentanil and monitored with full and
      processed electroencephalogram. Analgesia was quantified with subjective pain
      score to thermal stimulation. Ventilatory arrhythmias, as measured by the
      sedation apnea-hypopnea index (S-AHI), were scored as the number of apneas and
      hypopneas during two 1-hour periods on room air or 2 L/min nasal O2. RESULTS: All
      subjects tolerated the sedation and physostigmine without significant adverse
      effects. Sedation during placebo infusion resulted in clinically significant (S
      AHI > 15) ventilatory arrhythmias in 5 conditions in 3 subjects (2 on room air
      and then O2, and 1 on O2 only). Physostigmine did not significantly (P > 0.46)
      reduce the total number of ventilatory arrhythmias on either room air or O2 (13.4
      +/- 18.8 events/h [mean +/- SEM], 95% confidence interval [CI] = -9.9 to 62.7;
      and 6.2 +/- 8.0, 95% CI = -3.1 to 28.7, respectively). Physostigmine did reduce
      the S-AHI in all 5 instances of clinically significant ventilatory arrhythmias (S
      AHI decreased by 67.0 +/- 22.2; CI = 29.2-111.7; P = 0.04). CONCLUSIONS:
      Physostigmine does not appear to be useful as a pretreatment to prevent
      ventilatory arrhythmias during moderate sedation. However, it may be useful as a
      treatment for clinically significant ventilatory arrhythmias during moderate
      sedation.

PMID- 26200463
TI  - Asthma Is More Severe in Older Adults.
AB  - BACKGROUND: Severe asthma occurs more often in older adult patients. We
      hypothesized that the greater risk for severe asthma in older individuals is due
      to aging, and is independent of asthma duration. METHODS: This is a cross
      sectional study of prospectively collected data from adult participants (N=1130;
      454 with severe asthma) enrolled from 2002 - 2011 in the Severe Asthma Research
      Program. RESULTS: The association between age and the probability of severe
      asthma, which was performed by applying a Locally Weighted Scatterplot Smoother,
      revealed an inflection point at age 45 for risk of severe asthma. The probability
      of severe asthma increased with each year of life until 45 years and thereafter
      increased at a much slower rate. Asthma duration also increased the probability
      of severe asthma but had less effect than aging. After adjustment for most
      comorbidities of aging and for asthma duration using logistic regression,
      asthmatics older than 45 maintained the greater probability of severe asthma [OR:
      2.73 (95 CI: 1.96; 3.81)]. After 45, the age-related risk of severe asthma
      continued to increase in men, but not in women. CONCLUSIONS: Overall, the impact
      of age and asthma duration on risk for asthma severity in men and women is
      greatest over times of 18-45 years of age; age has a greater effect than asthma
      duration on risk of severe asthma.

PMID- 26200466
TI  - Radiographic Measurement of Rotational Deformity in Pelvic Fractures: A Novel
      Method With Validity and Reliability Testing.
AB  - OBJECTIVE: Measuring pelvic ring displacement on plain radiographs has focused on
      gap and translational displacements with little discussion of rotational
      displacement, likely because of measurement difficulties. Our hypothesis is that
      rotational displacement can be accurately measured on computer-reconstructed
      radiographs (CRRs) with good validity and reliability. METHODS: A Sawbones model
      was used to simulate common pelvic ring fracture patterns. CT scans were obtained
      and converted to CRRs simulating standard views. A technique of measuring axial
      rotation on the inlet view and sagittal rotation on the inlet/outlet views was
      developed. The novel rotational assessment techniques were then used by 8 senior
      orthopaedic residents and 3 fellowship-trained orthopaedic trauma surgeons on the
      CRR of each model. These measurements were then assessed for interobserver
      reliability and validity. Validity was tested by comparing the values obtained by
      the observers to the actual displacement as measured on CT scans. RESULTS: Newly
      described techniques for axial and sagittal rotational measurements showed
      excellent reliability with average confidence intervals of 1.8 degrees  and 3.4
      degrees , respectively. There was good validity of the technique, with the
      majority of the "true" measurements falling within the 95% confidence interval of
      the observer measurements. CONCLUSIONS: A new radiographic technique for
      measuring axial and sagittal rotational deformities shows excellent interobserver
      reliability and good validity. This technique offers a low-cost and low-radiation
      examination to assess this deformity, which is readily available in most clinical
      settings. This measurement system can be used in future clinical studies to
      assess the clinical implications of residual rotational displacement.

PMID- 26200467
TI  - A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered
      Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria.
AB  - BACKGROUND: Inappropriate treatment of malaria is widely reported particularly in
      areas where there is poor access to health facilities and self-treatment of
      fevers with anti-malarial drugs bought in shops is the most common form of care
      seeking. The main objective of the study was to examine the impact of introducing
      rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda,
      with the aim to increase appropriate treatment of malaria with artemisinin-based
      combination therapy (ACT) in patients seeking treatment for fever in drug shops.
      METHODS: A cluster-randomized trial of introducing mRDTs in registered drug shops
      was implemented in 20 geographical clusters of drug shops in Mukono district,
      central Uganda. Ten clusters were randomly allocated to the intervention
      (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to
      the control arm (presumptive treatment of fevers with ACT). Treatment decisions
      by providers were validated by microscopy on a reference blood slide collected at
      the time of consultation. The primary outcome was the proportion of febrile
      patients receiving appropriate treatment with ACT defined as: malaria patients
      with microscopically-confirmed presence of parasites in a peripheral blood smear
      receiving ACT or rectal artesunate, and patients with no malaria parasites not
      given ACT. FINDINGS: A total of 15,517 eligible patients (8672 intervention and
      6845 control) received treatment for fever between January-December 2011. The
      proportion of febrile patients who received appropriate ACT treatment was 72.9%
      versus 33.7% in the control arm; a difference of 36.1% (95% CI: 21.3 - 50.9),
      p<0.001. The majority of patients with fever in the intervention arm accepted to
      purchase an mRDT (97.8%), of whom 58.5% tested mRDT-positive. Drug shop vendors
      adhered to the mRDT results, reducing over-treatment of malaria by 72.6% (95% CI:
      46.7- 98.4), p<0.001) compared to drug shop vendors using presumptive diagnosis
      (control arm). CONCLUSION: Diagnostic testing with mRDTs compared to presumptive
      treatment of fevers implemented in registered drug shops substantially improved
      appropriate treatment of malaria with ACT. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01194557.

PMID- 26200470
TI  - International Association for Suicide Prevention.

PMID- 26200471
TI  - Structure modeling, synthesis and X-ray diffraction determination of an extra
      large calixarene-based coordination cage and its application in drug delivery.
AB  - An extra-large octahedral coordination cage (CIAC-114) was designed and modeled
      based on Co4-p-tert-butylsulfonylcalix[4]arene (Co4-(SC4A-SO2)) subunits and
      4,4',4''-(benzene-1,3,5-triyl-tris(benzene-4,1-diyl))tribenzoate (BBB) ligands
      via the isomorphic replacement approach built from an analogous cage structure
      with a smaller size. X-ray crystallography revealed that the crystals obtained
      through solvothermal synthesis exhibited the anticipated structure. Each CIAC-114
      cage is assembled by six tetranuclear Co4-(SC4A-SO2) units as vertices, which
      bear a four-fold rotational symmetry, and eight tripodal BBB ligands as linkers,
      which hold a D3h symmetry. Among its analogues CIAC-114 has the largest overall
      peripheral diameter of 5.4 nm and an internal cavity of 2.7 nm. After treatment
      by supercritical CO2, a single crystal sample of CIAC-114 transformed into
      amorphous material with the retention of the cage skeleton, which demonstrated
      good adsorption properties towards a small drug molecule, ibuprofen (Ibu),
      evidenced by IR spectroscopy, (1)H NMR spectroscopy, N2 sorption analysis, and
      drug release experiments. The Ibu release experiment in phosphate buffered saline
      solution (pH = 7.4) revealed that CIAC-114 exhibited a slow drug release
      behavior. 

PMID- 26200468
TI  - Accuracy of Urinary Neutrophil Gelatinase-Associated Lipocalin in Quantifying
      Acute Kidney Injury after Partial Nephrectomy in Patients with Normal
      Contralateral Kidney.
AB  - BACKGROUND: To evaluate the efficacy of urinary neutrophil gelatinase-associated
      lipocalin (uNGAL) for predicting the degree of acute kidney injury (AKI) in
      patients following partial nephrectomy (PN). METHODS: This prospective study
      included 176 patients who underwent open or laparoscopic PN for solid renal
      tumors between June 2013 and May 2014. Urine samples were collected
      preoperatively and at 3, 24, and 48 h after renal pedicle clamp removal. Changes
      in uNGAL levels were analyzed for all patients and between subgroups that were
      dichotomized based on preoperative eGFR values of <60 and >=60 mL/min/1.73m2,
      open and laparoscopic surgery, and according to the onset of AKI. Linear mixed
      models were used to investigate preoperative and perioperative features
      associated with postoperative uNGAL and eGFR changes at 6 months postoperatively.
      RESULTS: Among 146 patients included in the final analysis, 10 (6.8%) patients
      had preoperative eGFR <60 mL/min/1.73m2. In the overall group, uNGAL levels
      increased following PN. However, all subgroups demonstrated comparable changes in
      uNGAL levels over time. Multivariate analyses failed to reveal any correctable
      clinical features associated with postoperative uNGAL changes, whereas
      preoperative serum creatinine levels and the onset of AKI correlated with eGFR at
      6 months postoperatively. CONCLUSIONS: uNGAL levels may increase following PN.
      However, it does not appear to be a useful marker for quantifying the degree of
      AKI or predicting postoperative renal function in patients with normal
      contralateral kidney and relatively good preoperative renal function. Further
      analysis is necessary to assess the usefulness of uNGAL in patients with poor
      preoperative renal function.

PMID- 26200472
TI  - Synthetic peptides mimicking the binding site of human acetylcholinesterase for
      its inhibitor fasciculin 2.
AB  - Molecules capable of mimicking protein binding and/or functional sites present
      useful tools for a range of biomedical applications, including the inhibition of
      protein-ligand interactions. Such mimics of protein binding sites can currently
      be generated through structure-based design and chemical synthesis. Computational
      protein design could be further used to optimize protein binding site mimetics
      through rationally designed mutations that improve intermolecular interactions or
      peptide stability. Here, as a model for the study, we chose an interaction
      between human acetylcholinesterase (hAChE) and its inhibitor fasciculin-2 (Fas)
      because the structure and function of this complex is well understood. Structure
      based design of mimics of the hAChE binding site for Fas yielded a peptide that
      binds to Fas at micromolar concentrations. Replacement of hAChE residues known to
      be essential for its interaction with Fas with alanine, in this peptide, resulted
      in almost complete loss of binding to Fas. Computational optimization of the
      hAChE mimetic peptide yielded a variant with slightly improved affinity to Fas,
      indicating that more rounds of computational optimization will be required to
      obtain peptide variants with greatly improved affinity for Fas. CD spectra in the
      absence and presence of Fas point to conformational changes in the peptide upon
      binding to Fas. Furthermore, binding of the optimized hAChE mimetic peptide to
      Fas could be inhibited by hAChE, providing evidence for a hAChE-specific peptide
      Fas interaction.

PMID- 26200473
TI  - Cu-Oxide-Assisted Selective Pyrolysis of Organic Nanolayer on Patterned SiO2-Cu
      Surface.
AB  - Organic nanolayers attract much attention for the isolation and adhesion
      promotion of the Cu line and insulator in Cu interconnection of microelectronic
      devices. This paper proposes a strategy for selective formation of adhesion
      nanolayer on the insulator surface with etching it on Cu surface by Cu-oxide
      assisted pyrolysis. After deposition of a uniform polyelectrolyte layer on both
      SiO2 and Cu surfaces, heat treatment at 350  degrees C in ambient nitrogen was
      applied. Then, a larger thickness decrease was observed on the polyelectrolyte
      layer on Cu when compared to that on SiO2. According to the TDS and XPS analysis,
      the polyelectrolyte layer was relatively stable on SiO2 up to the intrinsic
      decomposition temperature of the material, but on the Cu surface it decomposed to
      volatile small molecules at a lower temperature due to Cu2O-assisted oxidization.
      This substrate dependent selective pyrolysis was examined for 100 nm width Cu
      lines and SiO2 spaces, and then a patterned polyelectrolyte layer on the SiO2
      surface was obtained with a single nanometer scale edge resolution. 

PMID- 26200474
TI  - Childhood-onset systemic lupus erythematosus: an update.
AB  - PURPOSE OF REVIEW: This is an update of the main studies published in the last
      year regarding biomarkers, advances in pathophysiology, lupus nephritis as well
      as outcomes and therapies in childhood-onset systemic lupus erythematosus (cSLE).
      RECENT FINDINGS: Some progress in the pathophysiology of cSLE was made in the
      past year. Although biomarkers were studied in lupus nephritis and
      neuropsychiatric lupus, none of the proposed biomarkers was shown to be a
      significant improvement over current disease measures. More encouraging was the
      research into creating an easy, rapid screening tool for neurocognitive
      dysfunction in cSLE. Two studies in health-related quality of life (HRQL)
      recognized its importance in determining outcome and found that ethnicity and
      obesity might significantly alter HRQL in cSLE patients. There were no
      prospective clinical trials involving cSLE patients. SUMMARY: A better
      understanding of pathophysiology may elucidate novel molecules as therapeutic
      targets in cSLE. Advances in the field of biomarkers may enable a more accurate
      prediction of clinical outcome, optimizing early interventions and therefore
      improving disease prognostics.

PMID- 26200475
TI  - Gray-scale and color Doppler sonographic features of complex fibroadenomas of the
      breast.
AB  - PURPOSE: To investigate gray-scale and color Doppler sonographic (US) features of
      complex fibroadenoma (FA), according to the Breast Imaging-Reporting and Data
      System (BI-RADS) lexicon. METHODS: From 2010 through 2013, 586 women with FAs
      were seen; 101 (17%) of those lesions were diagnosed as complex FAs on
      percutaneous needle biopsy or surgery. Among the patients with complex FAs, 67
      who had US examination results available were included in this study. In
      addition, the results from 98 women who had simple FAs were included as controls.
      US features were retrospectively analyzed by two breast radiologists in consensus
      for shape, margin, echogenicity, posterior acoustic pattern, boundary,
      orientation, and associated findings. They also reassessed the BI-RADS category
      for FAs. Color Doppler US examination results were classified according to the
      amount of vascularity as absent, moderate, or marked. RESULTS: Complex FA were
      larger than simple FAs were (14.5 cm versus 12.1 cm, p > 0.05). On univariate
      analysis, a round to irregular shape, an uncircumscribed margin, the presence of
      associated findings, and BI-RADS categorization as 4a and 4b were more frequently
      revealed in complex than in simple FAs (p < 0.05). Multivariate analysis revealed
      that the tumor margin was a predictive factor for complex FA (odds ratio: 6.08;
      95% confidence interval: 1.14-32.49, p < 0.05). On color Doppler US, the complex
      FAs had higher degrees of vascularity than simple FA (p < 0.05). CONCLUSIONS:
      Complex FAs, in comparison with simple FAs, tend to have more aggressive features
      and to be in higher BI-RADS categories on US examination.

PMID- 26200476
TI  - Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK
      Inhibitors for Metastatic Melanoma.
AB  - IMPORTANCE: The cutaneous adverse effects of the BRAF inhibitors vemurafenib and
      dabrafenib mesylate in the treatment of metastatic melanoma have been well
      reported. The addition of a MEK inhibitor to a BRAF inhibitor improves the
      blockade of the mitogen-activated protein kinase pathway. The combination of
      dabrafenib with the MEK inhibitor trametinib dimethyl sulfoxide (CombiDT therapy)
      increases response rate and survival compared with a BRAF inhibitor alone.
      Clinical trials have suggested that CombiDT therapy induces fewer cutaneous toxic
      effects than a single-agent BRAF inhibitor. To our knowledge, a direct comparison
      has not been performed before. OBJECTIVE: To compare the cutaneous toxic effects
      of BRAF inhibitor monotherapy and CombiDT therapy in a large cohort of patients.
      DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective cohort study from
      September 1, 2009, through November 30, 2013. The study population included 185
      Australian patients with unresectable stages IIIC and IV melanoma referred from
      Crown Princess Mary Cancer Care Centre who underwent review at the Department of
      Dermatology, Westmead Hospital. Of these, 119 patients received dabrafenib; 36,
      vemurafenib; and 30, CombiDT therapy. Data analysis were performed in December
      2013. MAIN OUTCOMES AND MEASURES: Multiple cutaneous adverse effects between BRAF
      inhibitor monotherapy and CombiDT therapy were identified and compared in a
      cohort of patients who underwent the same dermatologic assessment. RESULTS: The
      most common cutaneous adverse effects seen in patients receiving the single-agent
      BRAF inhibitor dabrafenib or vemurafenib included Grover disease (51 patients
      [42.9%] and 14 [38.9%], respectively [P = .67]), plantar hyperkeratosis (47
      [39.5%] and 14 [38.9%], respectively [P = .95]), verrucal keratosis (79 [66.4%]
      and 26 [72.2%], respectively [P = .51]), and cutaneous squamous cell carcinoma
      (31 [26.1%] and 13 [36.1%], respectively [P = .54]). Photosensitivity was more
      common with vemurafenib (14 patients [38.9%]) compared with dabrafenib (1 [0.8%];
      P < .001). Compared with dabrafenib, CombiDT therapy showed a higher frequency of
      folliculitis (12 patients [40.0%] vs. 8 [6.7%]; P < .001) and a significant
      decrease of cutaneous squamous cell carcinoma (0 vs. 31 [26.1%]; P < .001),
      verrucal keratosis (0 vs. 79 [66.4%]; P < .001), and Grover disease (0 vs. 51
      [42.9%]; P < .001). CONCLUSIONS AND RELEVANCE: This study confirms that the
      prevalence of cutaneous toxic effects differs among vemurafenib, dabrafenib, and
      CombiDT therapies. Cutaneous squamous cell carcinoma is the most concerning
      cutaneous toxic effect related to BRAF inhibitor monotherapy that did not appear
      with CombiDT therapy. Although CombiDT therapy has an improved profile of
      cutaneous toxic effects, continuous dermatologic assessments should be provided
      for all patients when receiving these treatments.

PMID- 26200478
TI  - Safety and Clinical Outcome of Catheter Ablation of Ventricular Arrhythmias Using
      Contact Force Sensing: Consecutive Case Series.
AB  - BACKGROUND: Poor catheter-to-myocardial contact can lead to ineffective ablation
      lesions and suboptimal outcome. Contact force (CF) sensing catheters in
      ventricular tachyarrhythmia (VT) ablations have not been studied for their long
      term efficacy. PURPOSE: The aim of this study was to compare CF ablation to
      manual ablation (MAN) and remote magnetic navigation (RMN) ablation for safety
      and efficacy in acute and long-term outcome. METHODS: A total of 239 consecutive
      patients who underwent VT ablation with the use of MAN, CF, or RMN catheters were
      included in this single-center cohort study from January 2007 until March 2014.
      The primary endpoints were procedural success, acute major complications, and VT
      recurrences at follow-up. The median follow-up period was 25 months. RESULTS:
      Acute success was achieved in 182 out of 239 procedures (76%). Acute success in
      manual ablation, CF ablation and RMN ablation was 71%, 71%, and 86%, respectively
      (P = 0.03). Major complications occurred in 3.3% and there were less major
      complications (P = 0.04) in the RMN group. After an initial successful procedure,
      66 of 182 patients (36%) had a recurrence during follow-up. This was not
      significantly different between groups. Using an intention-to-treat analysis, 124
      patients (52%) had a recurrence. The recurrence rate was lowest in the RMN group.
      CONCLUSION: The use of CF sensing catheters did not improve procedural outcome or
      safety profile in comparison to non-CF sensing ablation in this observational
      study of ventricular arrhythmia ablations.

PMID- 26200477
TI  - Noncoding RNA-guided recruitment of transcription factors: A prevalent but
      undocumented mechanism?
AB  - High-fidelity binding of transcription factors (TFs) to DNA target sites is
      fundamental for proper regulation of cellular processes, as well as for the
      maintenance of cell identity. Recognition of cognate binding motifs in the genome
      is attributed by and large to the DNA binding domains of TFs. As an additional
      mode of conferring binding specificity, noncoding RNAs (ncRNAs) have been
      proposed to assist associated TFs in finding their binding sites by interacting
      with either DNA or RNA in the vicinity of their target loci. However, a well
      documented example of such a mechanism was lacking until we recently reported
      that a ncRNA made by Epstein-Barr virus uses an RNA-RNA interaction with nascent
      transcripts generated from the viral genome to facilitate the recruitment of an
      interacting TF, PAX5, to viral DNA. This proof-of-principle finding suggests that
      cellular ncRNAs may likewise function in guiding interacting TFs to chromatin
      target sites. 

PMID- 26200479
TI  - Effect of Variations of Washing Solution Chemistry on Nanomaterial
      Physicochemical Changes in the Laundry Cycle.
AB  - Engineered nanoparticle (ENP) life cycles are strongly dependent on the life
      cycle of the nanoenhanced products in which they are incorporated. An important
      phase for ENP associated with textiles is washing. Using a set of liquid and
      powdered commercially available detergents that span a wide range of different
      chemistries, washing studies were performed with one "standard" nanoparticle
      suspended in wash solution to systematically investigate (changes to) particle
      size distribution, dissolution, reprecipitation (i.e., "new" particle formation),
      and complexation to particulate matter. Au ENPs were used as a "tracer" through
      the system. TEM and EDX analysis were performed to observe morphological and
      chemical changes to the particles, and single-particle ICP-MS was used to build a
      size distribution of particles in solution. Varying the washing solution
      chemistry was found to dictate the extent and rate of dissolution, particle
      destruction, surface chemistry change(s), and new particle formation. Detergent
      chemistry, dominated by oxidizing agents, was a major factor. The detergent form
      (i.e., powder vs liquid) was the other decisive factor, with powder forms
      providing available surfaces for precipitation and sorption reactions. Control
      experiments with AgNO3 indicated metallic Ag particles formed during the washing
      process from dissolved Ag, implying not all Ag-NPs observed in a textile washing
      study are indicative of released Ag-ENPs but can also be the result of sequential
      dissolution/reduction reactions.

PMID- 26200480
TI  - Added value of diffusion-weighted MRI in detection of cervical cancer recurrence:
      comparison with morphologic and dynamic contrast-enhanced MRI sequences.
AB  - PURPOSE: We aimed to evaluate the added value of diffusion-weighted imaging (DWI)
      to standard magnetic resonance imaging (MRI) for detecting post-treatment
      cervical cancer recurrence. The detection accuracy of T2-weighted (T2W) images
      was compared with that of T2W MRI combined with either dynamic contrast-enhanced
      (DCE) MRI or DWI. METHODS: Thirty-eight women with clinically suspected uterine
      cervical cancer recurrence more than six months after treatment completion were
      examined with 1.5 Tesla MRI including T2W, DCE, and DWI sequences. Disease was
      confirmed histologically and correlated with MRI findings. The diagnostic
      performance of T2W imaging and its combination with either DCE or DWI were
      analyzed. Sensitivity, positive predictive value, and accuracy were calculated.
      RESULTS: Thirty-six women had histologically proven recurrence. The accuracy for
      recurrence detection was 80% with T2W/DCE MRI and 92.1% with T2W/DWI. The
      addition of DCE sequences did not significantly improve the diagnostic ability of
      T2W imaging, and this sequence combination misclassified two patients as falsely
      positive and seven as falsely negative. The T2W/DWI combination revealed a
      positive predictive value of 100% and only three false negatives. CONCLUSION: The
      addition of DWI to T2W sequences considerably improved the diagnostic ability of
      MRI. Our results support the inclusion of DWI in the initial MRI protocol for the
      detection of cervical cancer recurrence, leaving DCE sequences as an option for
      uncertain cases.

PMID- 26200481
TI  - Apparent diffusion coefficient for discriminating metastatic lymph nodes in
      patients with squamous cell carcinoma of the head and neck.
AB  - PURPOSE: We aimed to evaluate the apparent diffusion coefficient (ADC) values of
      metastatic lymph nodes in patients with squamous cell carcinoma (SCC) of the head
      and neck. METHODS: Patients with metastatic lymph nodes underwent 1.5 Tesla
      diffusion-weighted magnetic resonance imaging (MRI). The ADC values of the
      histologically proven metastases were evaluated retrospectively and mean ADC
      values were compared using one-way analysis of variance test. Receiver operating
      characteristic analysis was performed to identify ADC threshold values. RESULTS:
      We included 33 patients (27 males, 6 females; mean age, 60.7 years) with 53
      metastatic lymph nodes in the study. Mean ADC values for nodal metastases of
      nasopharyngeal carcinoma (NPC) (n=7), oropharyngeal (n=12), laryngeal (n=27), and
      hypopharyngeal (n=7) carcinoma were (0.810+/-0.158)*10-3 mm2/s, (0.985+/
      0.099)*10-3 mm2/s, (1.037+/-0.150)*10-3 mm2/s, and (0.948+/-0.081)*10-3 mm2/s,
      respectively. The mean ADC values of nodal metastases of NPC were significantly
      lower than ADC values of laryngeal carcinoma (LSCC) (P = 0.002). An ADC value
      less than 0.890*10-3 mm2/s was found to facilitate differentiation of NPC from
      LSCC with a sensitivity of 71% and specificity of 85% (area under the curve,
      0.852). CONCLUSION: The mean ADC values showed significant differences between
      nodal metastases of NPC and LSCC. Considering SCCs as a single group may affect
      the accuracy of ADC-based differentiation. Location of the primary tumor should
      be taken into account and cutoff values should be determined separately for each
      anatomical location.

PMID- 26200482
TI  - Unusual benign solid neoplasms of the kidney: cross-sectional imaging findings.
AB  - Kidney neoplasms are common diseases with varying prognoses depending on the
      subtype of the tumor. The most common solid lesion of the kidney is renal cell
      carcinoma, and the treatment is typically surgical removal. With increasing use
      of cross-sectional imaging in the last two decades, the detection of renal
      lesions has significantly increased, especially in asymptomatic patients who are
      scanned for other reasons. In this article, we present the imaging findings of
      rare solid benign primary kidney neoplasms including renal leiomyoma, reninoma,
      carcinoid tumor, metanephric adenoma, solitary fibrous tumor of the kidney,
      lipomatous hemangiopericytoma of the kidney, renal schwannoma, inflammatory
      myofibroblastic tumor of the kidney, extramedullary hematopoiesis in the kidney,
      and extranodal renal Rosai-Dorfman disease. Accurate preoperative or prebiopsy
      diagnoses of these lesions are unusual; however, informed radiologists may
      sometimes be able to favorably change the patient management and treatment. 

PMID- 26200483
TI  - Effectiveness of second-opinion radiology consultations to reassess the cervical
      spine CT scans: a study on trauma patients referred to a tertiary-care hospital.
AB  - PURPOSE: A second opinion is a valuable resource in confirming proper medical
      diagnosis and treatment. This study evaluates the effectiveness of second-opinion
      radiology consultations to reassess the cervical spine computed tomography (CT)
      scans of the trauma patients referred to our hospital. METHODS: Cervical spine CT
      scans of 301 consecutive adult trauma patients, who were referred to our hospital
      from outside institutions, were analyzed. The emergency radiologists at our
      institution completed the over-read reports on the CT images obtained at the
      outside facilities. A single radiologist compared the outside- and over-read
      reports and determined the discrepancy of the radiologic reports. RESULTS: Based
      on the outside reports, 31% of the CT scans had cervical traumatic injury. In 92%
      of patients, the first-read and the over-read reports had consistent radiologic
      findings. About 90% of the positive, and 93% of the negative radiologic findings,
      were reported consistently in the over-read reports. Our analysis showed that the
      over-read reporting resulted in reassurance of negative findings in 63%;
      confirmation of positive findings in 29%; clearing a false diagnosis in 3%; and
      detection of a missed diagnosis in 5%. A rescan was done in 80% of patients with
      inconsistent and 20% of patients with consistent findings (P < 0.05). The most
      common missed radiologic findings in the first-reports were transverse and
      spinous process fractures and the most common misdiagnoses were dens fractures.
      CONCLUSION: For a service offering second-opinion consultations on cervical spine
      trauma, review of outside CT studies improves diagnosis and benefits patient
      care.

PMID- 26200484
TI  - PIRADS 2.0: what is new?

PMID- 26200485
TI  - A novel technique in the treatment of retroperitoneal lymphatic leakage: direct
      percutaneous embolization through the leakage pouch.
AB  - Lymphangiography and percutaneous embolization of injured lymphatics are
      minimally invasive and effective techniques for the diagnosis and treatment of
      thoracic and retroperitoneal lymphatic leaks. We present a 58-year-old man who
      had abdominal chylous collection developed after multiple abdominal surgeries.
      Retroperitoneal lymphatic duct leakage was detected by ultrasound-guided
      intranodal lymphangiography and treated successfully using computed tomography
      (CT)-guided transabdominal embolization with percutaneous N-butyl cyanoacrylate
      (NBCA) glue and percutaneous NBCA glue and coil embolization by directly
      catheterizing the leaking lymphatic channel through the chylous collection. To
      the best of our knowledge, this is the first report of a lymphatic leakage case
      treated by percutaneous direct catheterization and embolization of leaking
      lymphatic channels through the chylous fluid collection. 

PMID- 26200486
TI  - Yunnan Minority Eye Study Suggests That Ethnic Differences in Myopia Are Due to
      Different Environmental Exposures.

PMID- 26200487
TI  - Reversible Increase of Central Choroidal Thickness During High-Altitude Exposure.
AB  - PURPOSE: This study aimed to quantify the impact of high altitude on choroidal
      thickness and relate changes of altered choroidal blood flow to clinical
      parameters and acute mountain sickness (AMS). This work is related to the
      Tubingen High Altitude Ophthalmology (THAO) study. METHODS: Enhanced depth
      imaging spectral-domain optical coherence tomography was used to quantify macular
      choroidal layer thickness. Peripheral oxygen saturation, heart rate, and AMS
      scores were assessed in eight healthy subjects at baseline (altitude, 341 m) and
      at altitude (4559 m) for respective correlations. RESULTS: Longitudinal analysis
      revealed a significant (P = 0.011, ANOVA) increase in central choroidal thickness
      (CCT) during altitude exposure (CCT baseline = 271 +/- 9 MUm; CCT altitude = 288
      +/- 9 MUm) due to an increased choroidal blood flow. Incidence of AMS at altitude
      was 50%, peripheral oxygen saturation decreased by 25%, and heart rate increased
      by 39%. All changes were completely reversible after descent to low altitudes.
      CONCLUSIONS: A small but significant increase in choroidal thickness was observed
      upon acute altitude exposure to 4559 m. This increase in choroidal blood flow was
      not related to AMS and was fully reversible after return to low altitude.

PMID- 26200488
TI  - Multifocal Pupillography Identifies Changes in Visual Sensitivity According to
      Severity of Diabetic Retinopathy in Type 2 Diabetes.
AB  - PURPOSE: Retinal light sensitivity loss has been shown to occur prior to other
      signs of retinopathy and may predict the sight-threatening sequelae. A rapid,
      objective perimetric test could augment diabetes care. We investigated the
      clinical use of multifocal pupillographic objective perimetry (mfPOP) to identify
      patients with and without diabetic retinopathy. METHODS: Retinopathy severity was
      determined using the Early Treatment of Diabetic Retinopathy Study (ETDRS)
      standard for fundus photography. Pupillary responses were measured from both eyes
      of 25 adults with none to moderate diabetic retinopathy and 24 age-matched
      controls, using three mfPOP stimulus variants. Multifocal pupillographic
      objective perimetry stimulus variants tested 44 regions per eye arranged in a
      five-ring dartboard layout presented within either the central 30 degrees  or 60
      degrees  of fixation. Receiver operator characteristic (ROC) curves were produced
      from contraction amplitudes and time to peak responses. RESULTS: Regression
      analysis revealed that mean amplitude deviations were larger with severity of
      early retinopathy. On average, the longest delays were measured in patients with
      no retinopathy. The brightest wide-field stimuli produced the highest area under
      the ROC curve for differentiating eyes with no retinopathy from nonproliferative
      diabetic retinopathy (NPDR) and from healthy eyes (100 +/- 0.0%, mean +/- SE).
      The asymmetry in local delay deviations between eyes tended to produce higher
      sensitivity and specificity than amplitude deviations. CONCLUSIONS: Asymmetry in
      local response delays measured by mfPOP may provide useful information regarding
      the severity of diabetic retinopathy and may have clinical use as a rapid,
      noninvasive method for identifying functional loss even in the absence of NPDR.

PMID- 26200489
TI  - Central and Peripheral Corneal Power Change in Myopic Orthokeratology and Its
      Relationship With 2-Year Axial Length Change.
AB  - PURPOSE: We assessed the relationship between axial length (AL) change and
      corneal refractive power change induced by orthokeratology (ortho-k) contact lens
      wear. METHODS: A total of 88 myopic children aged 7 to 12 years were fitted with
      ortho-k lenses for overnight wear. Axial length was measured before enrollment
      and every 6 months after initiation of lens wear up to 24 months. Corneal apical
      refractive power and the mean power of each concentric ring from 0.5 to 7.2 mm in
      diameter at 0.1-mm intervals were measured using the Pentacam HR, and compared
      before and after 3 months of ortho-k lens wear. Summed corneal power change
      (SCPC) was defined as the sum of relative corneal power change within the central
      7.2-mm diameter corneal region. Age, baseline spherical equivalent refractive
      error (SERE), and SCPC were tested against 2-year AL growth in a stepwise
      multiple linear regression model. RESULTS: Of the 88 myopic children who were
      successfully fitted with ortho-k lenses, 64 completed the 2-year follow-up
      period. These completed test subjects experienced a mean axial growth of 0.37 +/-
      0.27 mm. Spherical equivalent refractive error and corneal apical refractive
      power decreased from baseline values of -2.88 +/- 0.96 diopters (D) and 43.47 +/-
      1.03 D to -0.20 +/- 0.85 D and 40.61 +/- 1.23 D, respectively, after 3 months of
      lens wear. The mean SCPC was 10.84 +/- 5.28 D . mm after 3 months. Axial
      elongation was significantly correlated with SCPC (standardized beta = -0.573, P
      < 0.001) and baseline age (standardized beta = -0.403, P < 0.001), but not with
      baseline SERE (beta = 0.081, P = 0.396). The regression model using SCPC and
      baseline age to predict axial elongation was acceptable (adjusted R2 = 0.56) and
      statistically significant (F2,61 = 41.09, P < 0.001). CONCLUSIONS: Axial
      elongation in children undergoing ortho-k therapy is negatively correlated with
      the age of the wearer and summed corneal power change from the central to the mid
      peripheral cornea. We speculate that axial elongation is influenced by the extent
      to which the retinal defocus profile is altered with ortho-k lens wear.
      (http://www.chictr.org number, ChiCTR-TNRC-11001210.).

PMID- 26200490
TI  - Microsaccades and Prediction of a Motor Act Outcome in a Dynamic Sport Situation.
AB  - PURPOSE: Microsaccades could indicate the place where our mind is unconsciously
      focusing, although our gaze is directed elsewhere. Many studies report the
      importance of microsaccades in visual scene perception, but none of them has
      addressed their relationship with the perception of a dynamic action and the
      prediction of its outcome. METHODS: Expert and novice table tennis players were
      asked to fixate their gaze on a precise spot while viewing the launch of a ball
      whose final landing had to be predicted. Four separate epochs of the action were
      considered for their information content. The correctness of the prediction and
      microsaccade statistics were measured in order to estimate the relationship
      between covert attention and predictions. RESULTS: Microsaccades rate showed a
      time course modulated by the different epochs, with a significant enhancement
      during the post-bounce. In this epoch, novices showed a significantly higher rate
      than experts when the responses were correct. Duration and amplitude were highest
      in the pre- and post-bounce periods and lowest in the other two. Mean
      microsaccades direction was toward the stimuli that most probably attracted the
      visual attention (ball or racket), whereas there was no relationship with the
      predicted side of the final bounce. CONCLUSIONS: Distribution of microsaccades
      can be influenced by attentional cues in a task-specific situation, revealing
      links between visuomotor performance and covert attention shifts in fast
      visuomotor perception. Microsaccade orientation is conditioned by objects that
      attract visual attention and not by the direction in which action is expected to
      be performed.

PMID- 26200491
TI  - Expansion of CTG18.1 Trinucleotide Repeat in TCF4 Is a Potent Driver of Fuchs'
      Corneal Dystrophy.
AB  - PURPOSE: To analyze the expansion of CTG18.1 allele associated with Fuchs'
      corneal dystrophy (FCD) in our large cohort of late-onset FCD cases. METHODS: CTG
      repeats within the CTG18.1 allele were estimated by short tandem repeat (STR) and
      triplet primed PCR (TP-PCR) assays in our large cohort of 574 late-onset FCD
      cases and 354 controls and large multigeneration familial cases. The age versus
      severity relationships were analyzed in FCD genotypes, namely, nonexpanded (N/N),
      monoallelic expansion (N/X), and biallelic expansion (X/X) with N <= 40 CTG
      monomers. The threshold for causality conferred by an expansion of CTG18.1 was
      identified by excluding the population of FCD cases who harbored an allele length
      equivalent to the maximum CTG monomers observed in the controls. RESULTS: The
      expanded CTG18.1 for (CTG)n>40 showed a strong association (P = 1.56 * 10(-82))
      with FCD. Importantly, we delineated the threshold of expansion to 103 CTG
      repeats above which the allele confers causality in 17.8% of FCD cases.
      Regression analyses demonstrated a significant correlation between disease
      severity and age in individuals who harbor either a monoallelic expansion or a
      biallelic expansion at (CTG) n > 40. These analyses helped predict FCD in two
      previously unaffected individuals based on their CTG18.1 expansion genotype.
      CONCLUSIONS: A monoallelic expansion of CTG18.1 contributes to increased disease
      severity and is causal at (CTG)n>103, whereas a biallelic expansion is sufficient
      to be causal for FCD at (CTG)n>40. This study highlights the largest contributory
      causal allele for FCD.

PMID- 26200492
TI  - In Vivo Foveal Development Using Optical Coherence Tomography.
AB  - PURPOSE: To characterize the time course of normal foveal development in vivo in
      term infants and young children using handheld spectral-domain optical coherence
      tomography (HH-SDOCT). METHODS: We obtained 534 HH-SDOCT scans from 261 infants,
      children, and young adults with a mean age of 4.9 years (range, 0-27 years). Each
      retinal layer was manually segmented in ImageJ and correlated with gestational
      age (GA) and visual acuity (VA). The developmental trajectories of each retinal
      layer at the fovea, parafovea, and perifovea were calculated using fractional
      polynomial modeling. RESULTS: The central macular thickness (CMT) increases
      logarithmically between birth and 48.6 months GA. The foveal ganglion cell (GCL),
      inner plexiform, inner nuclear (INL), and outer plexiform layers decrease in
      thickness exponentially until 18 months GA. Interestingly, the parafoveal and
      perifoveal GCL and INL thicknesses initially decrease until 17 months GA and then
      increase in thickness until 65.5 GA. The foveal outer nuclear layer, inner
      segment, and outer segment of the photoreceptors increase in thickness
      logarithmically until 32.4, 26.9, and 45.3 months GA, respectively. The
      parafoveal and perifoveal outer retinal layers increase in thickness more
      gradually until 146 months GA. The thickness of the outer retinal layers and CMT
      were strongly correlated with VA, with r = 0.54 (P < 0.0001) and r = 0.52 (P <
      0.0001), respectively. CONCLUSIONS: We have modeled for the first time the
      complex, nonlinear developmental trajectories for each retinal layer and
      demonstrate that development continues until adolescence. Our description of
      normal development will be helpful in diagnosing, monitoring, and understanding
      pediatric retinal disease.

PMID- 26200493
TI  - Handheld OCT Comes of Age.

PMID- 26200494
TI  - Optic Disc Ovality in Primary School Children in Beijing.
AB  - PURPOSE: The purpose of this study was to assess the ovality of the optic disc
      and its associations with myopia-related factors in primary school children in
      Beijing. METHODS: This longitudinal school-based study included 382 grade 1
      children and 299 grade 4 children who were followed for 2 years. Study
      participants underwent a comprehensive eye examination including
      autorefractometry, ocular biometry, and fundus photography. RESULTS: Fundus
      photographs were available for 562 children (82.5%). The mean optic disc ovality
      (maximal-to-minimal disc diameter) was 1.17 +/- 0.29 (range, 1.00-1.50). Oval
      discs defined by an ovality of >= 1.33 were detected in 37 children (prevalence:
      6.6%; 95% confidence interval: 4.5-8.6). In multivariate linear regression
      analysis, higher optic disc ovality index was significantly associated with older
      age (P = 0.001), female sex (P = 0.005), larger parapapillary beta zone (P <
      0.001), and shorter time spent indoors with studying (P = 0.003) and was
      marginally significant (P = 0.057), with greater increase in myopic refractive
      error from 2011 to 2013. From 2011 to 2013, myopic refractive error increased in
      the oval optic disc group by 1.03 +/- 0.99 diopters compared to 0.67 +/- 1.31
      diopters in the nonoval disc group. CONCLUSIONS: The prevalence of oval optic
      discs in Beijing school children was markedly higher than in the elderly Beijing
      Eye Study population (6.6% vs. 0.36%), paralleling the higher prevalence of
      myopia in school children. The association between oval optic discs and less time
      spent indoors with studying after adjusting for longitudinal change in myopic
      refractive error, age, sex and parapapillary beta zone may warrant further
      exploration of external factors associated with oval optic discs.

PMID- 26200495
TI  - Thickness of the Macula, Retinal Nerve Fiber Layer, and Ganglion Cell Layer in
      the Epiretinal Membrane: The Repeatability Study of Optical Coherence Tomography.
AB  - PURPOSE: To analyze the repeatability of measurements of the thicknesses of the
      macula, retinal nerve fiber layer (RNFL), and ganglion cell inner plexiform layer
      (GCIPL) using spectral-domain optical coherence tomography (SD-OCT) in the
      epiretinal membrane (ERM). METHODS: The prospective study analyzed patients who
      visited our retinal clinic from June 2013 to January 2014. An experienced
      examiner measured the thicknesses twice using macular cube 512 * 128 and optic
      disc cube 200 * 200 scans. The repeatability of the thicknesses of the macula,
      RNFL, and GCIPL were compared using the intraclass correlation coefficient (ICC)
      of two groups based on the central macular thickness (group A, <= 450 MUm; group
      B, > 450 MUm). RESULTS: A total of 88 patients were analyzed. The average
      thicknesses of the central macula, RNFL, and GCIPL were 256.5, 96.6, and 84.4
      MUm, respectively, in the normal fellow eye and 412.3, 94.6, and 56.7 MUm in the
      affected eye. The ICCs of the central macula, RNFL, and GCIPL were 0.995, 0.994,
      and 0.996, respectively, for the normal fellow eye and 0.991, 0.973, and 0.881
      for the affected eye. The average thicknesses of the central macula, RNFL, and
      GCIPL in group A were 360.9, 93.5, and 63.4 MUm, respectively, and the ICCs were
      0.997, 0.987, and 0.995. The thicknesses in group B were 489.5, 96.2, and 46.6
      MUm, respectively, and the ICCs were 0.910, 0.942, and 0.603, significantly lower
      repeatability compared with group A (P < 0.05). CONCLUSIONS: The macular contour
      change with the ERM results in low repeatability and tendency to be measured
      thinner in GCIPL thickness using SD-OCT. This can be explained by the unstable
      gaze of the patient due to decreased visual acuity and autosegmentation error
      following changes in the macula.

PMID- 26200496
TI  - Sarpogrelate, a 5-HT2A Receptor Antagonist, Protects the Retina From Light
      Induced Retinopathy.
AB  - PURPOSE: To determine if sarpogrelate, a selective 5-HT2A receptor antagonist, is
      protective against light-induced retinopathy in BALB/c mice. METHODS: BALB/c mice
      were dosed intraperitoneally with 5, 15, 30, 40, or 50 mg/kg sarpogrelate 48, 24,
      and 0 hours prior to bright light exposure (10,000 lux) as well as 24 and 48
      hours after exposure. Additionally, a single injection regimen was evaluated by
      injecting mice with 50 mg/kg sarpogrelate once immediately prior to light
      exposure. To investigate the potential for additive effects of serotonin receptor
      agents, a combination therapy consisting of sarpogrelate (15 mg/kg) and 8-OH-DPAT
      (1 mg/kg) was evaluated with the 5-day treatment regimen. Neuroprotection was
      characterized by the preservation of retinal thickness and function, measured by
      spectral-domain optical coherence tomography (SD-OCT) and electroretinography
      (ERG), respectively. RESULTS: Mice that were light damaged and injected with
      saline had significantly reduced outer retinal thickness, total retinal
      thickness, and ERG amplitudes compared with naive mice. A 5-day administration of
      15, 30, or 40 mg/kg of sarpogrelate was able to partially protect retinal
      morphology and full protection of retinal morphology was achieved with a 50 mg/kg
      dose. Both 15 and 30 mg/kg doses of sarpogrelate partially preserved retinal
      function measured by ERG, whereas 40 and 50 mg/kg doses fully preserved retinal
      function. Additionally, a single administration of 50 mg/kg sarpogrelate was able
      to fully preserve both retinal morphology and function. Administration of 15
      mg/kg of sarpogrelate and 1 mg/kg of 8-OH-DPAT together demonstrated an additive
      effect and fully preserved retinal morphology. CONCLUSIONS: A 5- or 1-day
      treatment with 50 mg/kg sarpogrelate can completely protect the retina of BALB/c
      mice from light-induced retinopathy. Partial protection can be achieved with
      lower doses starting at 15 mg/kg and protection increases in a dose-dependent
      manner. Treatment with low doses of sarpogrelate and 8-OH-DPAT elicits an
      additive effect that results in full protection of retinal morphology.

PMID- 26200497
TI  - Gene Expression-Based Predictive Models of Graft Versus Host Disease-Associated
      Dry Eye.
AB  - PURPOSE: To develop a predictive model based on inflammatory gene mRNA expression
      in conjunctival cells of graft versus host disease (GvHD)-associated dry eye (DE)
      patients, as well as to find meaningful correlations between gene signals and
      clinical signs. METHODS: Twenty GvHD-DE patients and 14 healthy controls were
      recruited. Patients discontinued medications for 1 week before examination. Dry
      eye-related symptoms and signs were recorded, and conjunctival epithelial cells
      were collected by impression cytology after spending 20 minutes under standard
      conditions within a Controlled Environmental Research Laboratory. Gene expression
      of inflammatory molecules was determined by polymerase chain reaction, and the
      results were correlated with clinical signs. Shrinkage discriminant analysis,
      support vector machine, and k-nearest neighbor classifier methods were used to
      develop predictive models that were validated considering accuracy, calibration,
      and discriminant capability. RESULTS: Out of the 84 genes analyzed, 34 showed
      significant differences in expression. IL-6, IL-9, CCL24, CCL18, IL-10, IFN
      gamma, and CCL2 were highly increased (>6-fold); 26 genes were moderately
      upregulated (2- to 6-fold), whereas EGFR was downregulated (2.63 fold) in GvHD-DE
      samples. A panel based on EGFR, IL-6, IL-9, and NAMPT had an area under the
      receiver operating characteristic curve of 0.994, a sensitivity of 100%, and a
      specificity of 92.9%. EGFR expression correlated negatively with ocular surface
      damage markers, while IL-6, IL-9, and NAMPT correlated positively with these
      tests. CONCLUSIONS: EGFR, IL-6, IL-9, and NAMPT have the greatest potential as
      diagnostic biomarkers, with excellent sensitivity, specificity, and clinical
      relevance to the ocular surface status of GvHD.

PMID- 26200498
TI  - The Noninflammatory Phenotype of Neutrophils From the Closed-Eye Environment: A
      Flow Cytometry Analysis of Receptor Expression.
AB  - PURPOSE: In the closed-eye environment (during sleep), there is an influx of
      neutrophils into the tear film, and the phenotype of these cells has yet to be
      characterized. This study was conducted to investigate the response of tear-film
      neutrophils to inflammatory stimuli. METHODS: Immediately upon awakening, cells
      from healthy participants (n = 12) were collected using a gentle eye-wash with
      PBS. Tear-film neutrophils were counted and cell viability was determined.
      Neutrophils were also isolated from blood by density-gradient centrifugation.
      Tear-film and blood-isolated neutrophils were stimulated with phorbol myristate
      acetate (PMA), lipopolysaccharide (LPS), or N-Formyl-L-methionyl-L-leucyl-L
      phenylalanine (fMLP). Changes in the expression of macrophage-1 antigen,
      intercellular adhesion molecule-1 (ICAM-1), CD66b (a degranulation membrane
      marker), C3aR (complement C3a receptor), CD45 (leukocyte common antigen) as well
      as reactive oxygen species (using dichlorodihydro-fluorescein diacetate) were
      characterized by flow cytometry. RESULTS: Hundreds of thousands of leukocytes
      were collected upon awakening. Tear-film neutrophils were alive as shown by
      trypan blue and propidium iodide (PI) exclusion. While tear-film neutrophils were
      able to mount an oxidative response, stimulation with LPS, PMA, or fMLP did not
      induce receptor upregulation. This lack of response to stimulus with tear-film
      neutrophils was significantly different from that of blood-isolated neutrophils.
      Incubation in the presence of tear film proteins did not affect the tear-film
      neutrophil response to stimuli. CONCLUSIONS: Our results indicate that while tear
      film neutrophils are alive, they do not respond to inflammatory stimuli in the
      same manner as blood-isolated neutrophils. This refractory phenotype may be due
      to exposure to anti-inflammatory factors present in the tear film.

PMID- 26200500
TI  - Association of Genetic Variations in TNFSF15 With Acute Anterior Uveitis in
      Chinese Han.
AB  - PURPOSE: T cells play an important role in the pathogenesis of uveitis. Recent
      studies have indicated that the TNFSF15 gene that encodes the TL1A protein can
      regulate the differentiation and activation of T cells. TNFSF15 gene
      polymorphisms have been found to be associated with several autoimmune disorders.
      A possible association of TNFSF15 with acute anterior uveitis (AAU) has not yet
      been reported and was therefore the purpose of our study. METHODS: Eight single
      nucleotide polymorphisms (SNPs) were examined using TaqMan SNP Genotyping Assay
      or PCR-restriction fragment length polymorphism in 983 AAU patients and 1128
      healthy controls. Genotype distributions and allele frequencies were compared
      using chi2 analysis between AAU patients and healthy controls. Stratified
      analysis was also performed according to ankylosing spondylitis (AS) status. The
      TNFSF15 mRNA expression was quantified by real-time PCR. RESULTS: A significantly
      decreased frequency of the TT genotype in TNFSF15-rs3810936 was found in AAU
      patients (P = 6.36 * 10(-6), corrected P[Pc] = 1.52 * 10(-4), OR = 0.6, 95% CI =
      0.5-0.8). Stratification according to AS status did not reveal a difference
      concerning the association with TNFSF15-rs3810936. None of the other TNFSF15 SNPs
      tested were associated with AAU. CONCLUSIONS: This study shows an association
      between TNFSF15-rs3810936 and AAU and suggests that the TL1A/DR3 pathway may be
      implicated in the pathogenesis of this disease.

PMID- 26200499
TI  - Inherited Photoreceptor Degeneration Causes the Death of Melanopsin-Positive
      Retinal Ganglion Cells and Increases Their Coexpression of Brn3a.
AB  - PURPOSE: To study the population of intrinsically photosensitive retinal ganglion
      cells (melanopsin-expressing RGCs, m+RGCs) in P23H-1 rats, a rat model of
      inherited photoreceptor degeneration. METHODS: At postnatal (P) times P30, P365,
      and P540, retinas from P23H dystrophic rats (line 1, rapid degeneration; and line
      3, slow degeneration) and Sprague Dawley (SD) rats (control) were dissected as
      whole-mounts and immunodetected for melanopsin and/or Brn3a. The dendritic
      arborization of m+RGCs and the numbers of Brn3a+RGCs and m+RGCs were quantified
      and their retinal distribution and coexpression analyzed. RESULTS: In SD rats,
      aging did not affect the population of Brn3a+RGCs or m+RGCs or the percentage
      that showed coexpression (0.27%). Young P23H-1 rats had a significantly lower
      number of Brn3a+RGCs and showed a further decline with age. The population of
      m+RGCs in young P23H-1 rats was similar to that found in SD rats and decreased by
      22.6% and 28.2% at P365 and P540, respectively, similarly to the decrease of the
      Brn3a+RGCs. At these ages the m+RGCs showed a decrease of their dendritic
      arborization parameters, which was similar in both the P23H-1 and P23H-3 lines.
      The percentage of coexpression of Brn3a was, however, already significantly
      higher at P30 (3.31%) and increased significantly with age (10.65% at P540).
      CONCLUSIONS: Inherited photoreceptor degeneration was followed by secondary loss
      of Brn3a+RGCs and m+RGCs. Surviving m+RGCs showed decreased dendritic
      arborization parameters and increased coexpression of Brn3a and melanopsin,
      phenotypic and molecular changes that may represent an effort to resist
      degeneration and/or preferential survival of m+RGCs capable of synthesizing
      Brn3a.

PMID- 26200501
TI  - Characterization of Abnormal Optic Nerve Head Morphology in Albinism Using
      Optical Coherence Tomography.
AB  - PURPOSE: To characterize abnormalities in three-dimensional optic nerve head
      (ONH) morphology in people with albinism (PWA) using spectral-domain optical
      coherence tomography (SD-OCT) and to determine whether ONH abnormalities relate
      to other retinal and clinical abnormalities. METHODS: Spectral-domain OCT was
      used to obtain three-dimensional images from 56 PWA and 60 age- and sex-matched
      control subjects. B-scans were corrected for nystagmus-associated motion
      artefacts. Disc, cup, and rim ONH dimensions and peripapillary retinal nerve
      fiber layer (ppRNFL) thickness were calculated using Copernicus and ImageJ
      software. RESULTS: Median disc areas were similar in PWA (median = 1.65 mm2) and
      controls (1.71 mm2, P = 0.128), although discs were significantly elongated
      horizontally in PWA (P < 0.001). In contrast, median optic cup area in PWA (0.088
      mm2) was 23.7% of that in controls (0.373 mm2, P < 0.001), with 39.4% of eyes in
      PWA not demonstrating a measurable optic cup. This led to significantly smaller
      cup to disc ratios in PWA (P < 0.001). Median rim volume in PWA (0.273 mm3) was
      136.6% of that in controls (0.200 mm3). The ppRNFL was significantly thinner in
      PWA compared with controls (P < 0.001), especially in the temporal quadrant. In
      PWA, ppRNFL thickness was correlated to ganglion cell thickness at the central
      fovea (P = 0.007). Several ONH abnormalities, such as cup to disc ratio, were
      related to higher refractive errors in PWA. CONCLUSIONS: In PWA, ocular
      maldevelopment is not just limited to the retina but also involves the ONH.
      Reduced ppRNFL thickness is consistent with previous reports of reduced ganglion
      cell numbers in PWA. The thicker rim volumes may be a result of incomplete
      maturation of the ONH.

PMID- 26200502
TI  - Autosomal Recessive Bestrophinopathy Is Not Associated With the Loss of
      Bestrophin-1 Anion Channel Function in a Patient With a Novel BEST1 Mutation.
AB  - PURPOSE: Mutations in BEST1, encoding bestrophin-1 (Best1), cause autosomal
      recessive bestrophinopathy (ARB). Encoding bestrophin-1 is a pentameric anion
      channel localized to the basolateral plasma membrane of the RPE. Here, we
      characterize the effects of the mutations R141H (CGC > CAC) and I366fsX18
      (c.1098_1100+7del), identified in a patient in our practice, on Best1
      trafficking, oligomerization, and channel activity. METHODS: Currents of Cl- were
      assessed in transfected HEK293 cells using whole-cell patch clamp. Best1
      localization was assessed by confocal microscopy in differentiated, human-induced
      pluripotent stem cell-derived RPE (iPSC-RPE) cells following expression of
      mutants via adenovirus-mediated gene transfer. Oligomerization was evaluated by
      coimmunoprecipitation in iPSC-RPE and MDCK cells. RESULTS: Compared to Best1,
      Best1 I366fsX18 currents were increased while Best1 R141H Cl- currents were
      diminished. Coexpression of Best1 R141H with Best1 or Best1 I366fsX18 resulted in
      rescued channel activity. Overexpressed Best1, Best1 R141H, and Best1 I366fsX18
      were all properly localized in iPSC-RPE cells; Best1 R141H and Best1 I366fsX18
      coimmunoprecipitated with endogenous Best1 in iPSC-RPE cells and with each other
      in MDCK cells. CONCLUSIONS: The first 366 amino acids of Best1 are sufficient to
      mediate channel activity and homo-oligomerization. The combination of Best1 and
      Best1 R141H does not cause disease, while Best1 R141H together with Best1
      I366fsX18 causes ARB. Since both combinations generate comparable Cl- currents,
      this indicates that ARB in this patient is not caused by a loss of channel
      activity. Moreover, Best1 I366fsX18 differs from Best1 in that it lacks most of
      the cytosolic C-terminal domain, suggesting that the loss of this region
      contributes significantly to the pathogenesis of ARB in this patient.

PMID- 26200503
TI  - Visual Prognosis of Eyes Recovering From Macular Hole Surgery Through Automated
      Quantitative Analysis of Spectral-Domain Optical Coherence Tomography (SD-OCT)
      Scans.
AB  - PURPOSE: To determine the value of topographic spectral-domain optical coherence
      tomography (SD-OCT) imaging features assessed after macular hole repair surgery
      in predicting visual acuity (VA) outcomes. METHODS: An automated algorithm was
      developed to topographically outline and quantify area, extent, and location of
      defects in the ellipsoid zone (EZ) band and inner retina layers in SD-OCT scans.
      We analyzed the correlation of these values with VA in longitudinal observations
      from 35 patients who underwent successful macular hole surgery, in their first
      observation after surgery (within 2 months), and in a single observation within 6
      to 12 months after surgery. Image features assessed at the first visit after
      surgery were also investigated as possible predictors of future VA improvement.
      RESULTS: Significant correlation with longitudinal VA was found for the extent,
      circularity, and ratio of defects in EZ band at the fovea and parafoveal regions.
      The ratio of defects in EZ band at the fovea, temporal-inner, and inferior-inner
      macula regions showed significant strong correlation with VA within 6 to 12
      months post surgery. Patients with worse vision outcome at such time also had a
      significantly higher rate of inner retinal defects in the superior-outer region
      in their first postsurgery observation. CONCLUSIONS: A lowering extent of EZ band
      defects in the foveal and parafoveal regions is a good indicator of postsurgery
      VA recovery. Attention should also be given to postsurgical alterations in the
      inner retina, as patients with more extensive atrophic changes appear to have
      slower or worse VA recovery despite closure of the macular hole.

PMID- 26200504
TI  - Lymph node metastasis in differentiated-type early gastric cancer: a single
      center retrospective analysis of surgically resected cases.
AB  - BACKGROUND: Lymph node metastasis (LNM) from early gastric cancer (EGC) is rare,
      especially for differentiated-type EGC. However, LNM has been reported in a few
      cases after endoscopic curative resection of differentiated-type EGC. This study
      aimed to evaluate LNM risk factors to identify those that should be considered
      during the preoperative evaluation of differentiated-type EGC. PATIENTS AND
      METHODS: A total of 976 EGC patients who underwent radical gastrectomy were
      reviewed in this study. Univariate and multivariate analyses were used to analyze
      the predictive factors for LNM based on the histology of the differentiated-type
      EGC cases. RESULTS: Differentiated-type EGC was observed in 59% of the cases. The
      rate of LNM was 6.6% (38/576 patients) in the differentiated-type EGC cases.
      Macroscopic shape, ulcers, tumor size, deeper invasion and lymphovascular
      invasion were shown to be related to LNM in differentiated-type EGC. Multivariate
      analysis revealed that size, depth, ulceration and lymphovascular invasion were
      independent predictors of LNM in differentiated-type EGC. When lymphovascular
      invasion was absent, the presence of one or more of the risk factors of ulcer
      lesions, tumor size >30 mm and submucosal invasion increased the rate of LNM.
      Thirteen patients who underwent radical gastrectomy were shown to have
      differentiated-type EGC with LNM that met the standard and expanded criteria of
      endoscopic submucosal dissection. CONCLUSIONS: As endoscopic resection is widely
      used, it is important to clarify the clinical significance of LNM in
      differentiated-type EGC and to screen for LNM with this incidence in mind and to
      follow the clinical courses of such cases, especially in China.

PMID- 26200505
TI  - BDNF, via truncated TrkB receptor, modulates GlyT1 and GlyT2 in astrocytes.
AB  - Glycine transporters (GlyT), GlyT1 and GlyT2, are responsible for the termination
      of glycine-mediated synaptic activity through removal of neurotransmitter from
      synaptic cleft. Brain-derived neurotrophic factor (BDNF) activates its high
      affinity tropomyosin-related kinase (Trk) receptors, namely TrkB, which includes
      full length (TrkB-FL) and truncated (TrkB-T) isoforms. In this article we
      evaluated the influence of BDNF upon the activity of glycine transporters in
      astrocytes. We report that BDNF decreases GlyT1- and GlyT2- mediated [(3)
      H]glycine transport in primary cultures of astrocytes from rat cerebral cortex.
      BDNF decreased Vmax but not Km values of transport, which suggests that BDNF
      induces transporter internalization. Accordingly, dynasore, an inhibitor of
      dynamin/clathrin-dependent endocytosis, prevented the influence of BDNF upon GlyT
      mediated transport. While quantifying mRNA and protein levels, we detected a
      predominance of truncated isoforms over the TrkB-FL receptor. The effect of BDNF
      was not abolished by specific inhibitors of PLCgamma, PI3K and MAPK, indicating
      that it did not occur through TrkB-FL canonical pathways. However, BDNF action
      was lost in the presence of a Rho family-specific blocker (toxin B), a signaling
      pathway that has been associated to TrkB-T1. Furthermore, the effect of BDNF was
      abolished upon TrkB-T knockdown in astrocytes by RNA interference.
      Immunofluorescence assays confirmed an increased GlyT expression in endosomes
      upon BDNF incubation, which was prevented in the presence of either dynasore or
      toxin B. We conclude that BDNF, acting on TrkB-T1 receptors, inhibits glycine
      uptake in astrocytes by promoting GlyT internalization through a Rho-GTPase
      activity dependent mechanism.

PMID- 26200506
TI  - Do HOXB13 and P63 have a role in differentiating poorly differentiated prostatic
      carcinoma from urothelial high-grade carcinoma?
AB  - Poorly differentiated prostatic carcinoma may overlap with high-grade urothelial
      carcinoma; a distinction is a must as treatments differ. This study aims to
      evaluate traditional (PSA and HMWCK) and relatively novel (P63 and HOXB13)
      markers in distinguishing them; and to evaluate their role in the diagnosis of
      challenging cases. Sections from: diagnosed group includes 65 prostatic and
      urothelial carcinoma cases were stained with PSA, HMWCK, P63, and HOXB13.
      Sensitivity, specificity, and accuracy were evaluated. The second group includes
      25 challenging cases which were stained first by PSA and HMWCK, then solved the
      problematic cases with P63 and HOXB13. PSA and HMWCK were sensitive and specific
      for prostatic and urothelial carcinomas, respectively, but the sensitivity and
      accuracy were higher for P63 and HOXB13. By using the traditional markers, 17
      cases were diagnosed in the second group while the remaining eight cases need the
      novel markers to be diagnosed. A confident diagnosis can be established in the
      majority of cases of poorly differentiated carcinoma in either prostatic or
      urothelial by using a panel of PSA and HMWCK. In some problematic cases, an
      extended panel including P63 and HOXB13 is helpful in resolving the diagnosis. 

PMID- 26200507
TI  - Determination of five sesquiterpenoids in Xingnaojing injection by quantitative
      analysis of multiple components with a single marker.
AB  - A quantitative analysis of multiple components with a single-marker method was
      established for the simultaneous determination of five sesqutiterpenoids in
      Xingnaojing injection. This method was established with Xingnaojing injection
      determined by high-performance liquid chromatography coupled with diode array
      detection. The durability and system suitability of the established method were
      evaluated, and the reliable relative correction factors were obtained with
      curdione selected as an internal reference. The contents of the five components
      in all Xingnaojing injections were determined by external standard method and the
      contents of curcumenone, curcumenol, curzerenone, and germacrone were also
      calculated with the obtained relative correction factors. Then, relative error
      was investigated to estimate the difference of the two methods. As a result, the
      established new method possesses good adaptability, and there is no significant
      difference between the two methods, except for the content of curzerenone in
      eight samples. To put the established method into practice, the limits of
      quantitation of the established method of the five components were proposed and
      defined. Thus, the developed methodology can also be utilized to the quality
      evaluation of Xingnaojing injection, in spite of the difference found in the
      content of curzerenone between the external standard method and the newly
      established method. 

PMID- 26200508
TI  - LONG-TERM EFFICACY OF SYSTEMIC INFLIXIMAB IN RECALCITRANT RETINAL VASCULITIS.
AB  - PURPOSE: To evaluate the efficacy of systemic infliximab for the induction of
      remission in patients with retinal vasculitis, inadequately responsive to other
      immunomodulatory therapy, based on fluorescein angiography grading for retinal
      vasculitis evaluation. METHODS: We analyzed 60 patients with retinal vasculitis,
      from the Massachusetts Eye Research and Surgery Institution in Cambridge, MA.
      Response to therapy was based on analysis of serial fluorescein angiography and
      fundus photography, including a baseline angiogram before initiation of
      infliximab. RESULTS: Sixty patients received infliximab therapy between July 2007
      and July 2012 at Massachusetts Eye Research and Surgery Institution for a
      diagnosis of retinal vasculitis. All had previously showed a poor clinical
      response to other immunomodulatory regimens, or ceased therapy due to intolerable
      side effects. The initial dose of infliximab was 5 mg/kg in all patients and
      remained at this dose for the extent of treatment in 57 (95%) patients. At 6
      months, 45 of 51 (88.23%) patients were maintaining remission with therapy, 5
      (9.8%) were in partial remission, and 1 patient had failed. At 12 months, 39 of
      39 (100%) patients were maintaining remission with therapy. CONCLUSION:
      Infliximab is effective for the treatment of recalcitrant noninfectious retinal
      vasculitis, refractory to conventional immunomodulatory therapy.

PMID- 26200509
TI  - LENS CAPSULAR FLAP TRANSPLANTATION IN THE MANAGEMENT OF REFRACTORY MACULAR HOLE
      FROM MULTIPLE ETIOLOGIES.
AB  - PURPOSE: To report the clinical results of lens capsular flap transplantation in
      refractory macular hole (MH). METHODS: This retrospective, interventional,
      consecutive case series included 20 eyes with persistent MH after previous
      standard MH surgery. All eyes underwent vitrectomy, lens anterior or posterior
      capsule transplantation into the MH, gas tamponade, and a 1-week postoperative
      head down. Structural and functional changes were evaluated. RESULTS: The
      predisposing conditions to surgical failure included high myopia with MH and
      retinal detachment in four eyes, MH after myopic foveoschisis surgery in one eye,
      high myopia with a large MH in one eye, proliferative diabetic retinopathy with
      MH in three eyes, MH with severe retinal detachment in one eye, retinal
      detachment with concurrent peripheral breaks and MH in one eye, and large or
      chronic MH in nine eyes. Macular hole was closed in all the 10 eyes receiving
      anterior capsular flap transplantation. In the 10 eyes with posterior capsular
      flap transplantation, MH was closed in 5, partially closed in 3, and not closed
      in 2. Visual acuity in logarithm of minimal angle of resolution improved from
      1.53 +/- 0.39 preoperatively to 1.07 +/- 0.35 postoperatively. CONCLUSION: Lens
      capsular flap transplantation may close the MH and improve visual outcome in the
      majority cases of refractory MH.

PMID- 26200510
TI  - PREDICTING RESPONSE OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION TO BEVACIZUMAB
      BASED ON SPECTRALIS OPTICAL COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To identify baseline optical coherence tomography factors in exudative
      age-related macular degeneration that predict response to bevacizumab injections.
      METHODS: Patients underwent spectral domain optical coherence tomography at
      diagnosis and the width, height, area, and location of the subretinal fluid,
      intraretinal fluid, pigment epithelial detachment, and subretinal tissue were
      measured. The location and size of photoreceptor and the loss of retinal pigment
      epithelium were recorded as well as quantitative retinal measurements. Patients
      received three consecutive monthly injections of bevacizumab after which their
      best-corrected visual acuity was recorded. RESULTS: Overall 105 eyes of 105
      patients aging 88 +/- 8.6 years were included. In univariate correlational
      analyses, only subretinal fluid width demonstrated a significant positive
      correlation with improved best-corrected visual acuity (R = 0.230, P = 0.018).
      Eyes with intraretinal fluid (P = 0.020) and retinal pigment epithelial loss (P =
      0.009) located in the subfoveal (as opposed to the juxtafoveal area)
      demonstrating worst visual outcomes. In stepwise backwards regression, the
      subretinal fluid width and intraretinal fluid location were the only parameters
      that remained significant explaining 9.23% of the variation in delta best
      corrected visual acuity scores. CONCLUSION: Improvement in best-corrected visual
      acuity after three injections of bevacizumab can be predicted from optical
      coherence tomography measurements. Specifically, the authors identified
      subretinal fluid width and intraretinal fluid location as significant markers.

PMID- 26200511
TI  - RETROSPECTIVE REVIEW OF LUCENTIS "TREAT AND EXTEND" PATTERNS AND OUTCOMES IN AGE
      RELATED MACULAR DEGENERATION.
AB  - PURPOSE: To assess patterns and outcomes of a "Treat and Extend" dosing regimen
      of ranibizumab in patients with age-related macular degeneration. METHODS: Three
      hundred and thirty two treatment-naive age-related macular degeneration patients
      starting therapy with ranibizumab between January 1, 2011, and June 30, 2012, at
      the Ivey Eye Institute were reviewed, and 79 met inclusion criteria. Patients on
      Treat and Extend dosing regimen underwent an induction phase with monthly
      injections and then moved onto an extension phase. Change in visual acuity and
      central retinal thickness during the induction and extension phases were
      recorded. RESULTS: During the induction phase, patients had a significant gain in
      vision and decrease in central retinal thickness (+8.4 letters, P < 0.001 and 
      81.3 MUm, P < 0.001). During the extension phase, patients did not have
      significant change in vision (-0.5 letters, P = 0.81) and did not have
      significant change in central retinal thickness (-11.5 MUm, P = 0.17). The
      average extension interval between treatments was 47.7 days, with patients
      receiving an average of 8.6 injections per year. Cost analysis showed it cost US
      $16,659 to treat 1 patient in the first year on Treat and Extend dosing regimen
      compared with US $20,614 on monthly dosing. CONCLUSION: Treat and Extend dosing
      regimen allows similar visual outcomes to monthly dosing, while reducing the
      total number of injections, visits, and overall cost.

PMID- 26200512
TI  - ADAPTIVE OPTICS IMAGING OF FOVEAL SPARING IN GEOGRAPHIC ATROPHY SECONDARY TO AGE
      RELATED MACULAR DEGENERATION.
AB  - BACKGROUND: To describe adaptive optics (AO) imaging of foveal sparing in
      geographic atrophy (GA) secondary to age-related macular degeneration. METHODS:
      Flood-illumination AO infrared (IR) fundus images were obtained in four
      consecutive patients with GA using an AO retinal camera (rtx1; Imagine Eyes).
      Adaptive optics IR images were overlaid with confocal scanning laser
      ophthalmoscope near-IR autofluorescence images to allow direct correlation of en
      face AO features with areas of foveal sparing. Adaptive optics appearance of GA
      and foveal sparing, preservation of functional photoreceptors, and cone densities
      in areas of foveal sparing were investigated. RESULTS: In 5 eyes of 4 patients
      (all female; mean age 74.2 +/- 11.9 years), a total of 5 images, sized 4 degrees 
      * 4 degrees , of foveal sparing visualized on confocal scanning laser
      ophthalmoscope near-IR autofluorescence were investigated by AO imaging. En face
      AO images revealed GA as regions of inhomogeneous hyperreflectivity with
      irregularly dispersed hyporeflective clumps. By direct comparison with adjacent
      regions of GA, foveal sparing appeared as well-demarcated areas of reduced
      reflectivity with less hyporeflective clumps (mean 14.2 vs. 3.2; P = 0.03). Of
      note, in these areas, en face AO IR images revealed cone photoreceptors as
      hyperreflective dots over the background reflectivity (mean cone density 3,271 +/
      1,109 cones per square millimeter). Microperimetry demonstrated residual
      function in areas of foveal sparing detected by confocal scanning laser
      ophthalmoscope near-IR autofluorescence. CONCLUSION: Adaptive optics allows the
      appreciation of differences in reflectivity between regions of GA and foveal
      sparing. Preservation of functional cone photoreceptors was demonstrated on en
      face AO IR images in areas of foveal sparing detected by confocal scanning laser
      ophthalmoscope near-IR autofluorescence.

PMID- 26200513
TI  - RETINAL LESION EVOLUTION IN SUSAC SYNDROME.
AB  - PURPOSE: To describe retinal lesion development in Susac syndrome during acute,
      postacute, and late phases of the disease. METHODS: Cross-sectional study of four
      patients with Susac syndrome and longitudinal short-interval case study of one
      additional patient. Retinal changes were analyzed with high-resolution spectral
      domain optical coherence tomography and retinal fluorescein angiography. RESULTS:
      Retinal Susac syndrome lesions comprise four different lesion sections, which can
      be distinguished in acute and postacute phases of the disease: a primary section
      at the site of branch retinal artery occlusion, which spans more layers than
      supplied by the affected vessel; hypoxic sections from superficial and deep
      capillary networks; and an axonal damage section with degenerating axons from
      perished ganglion cells in the main and hypoxic sections. In the later stages,
      main and hypoxic lesion sections can no longer be distinguished, and both show
      degeneration from outer plexiform to retinal nerve fiber layers. CONCLUSION: The
      dynamics of lesion development and morphologically distinct lesion sections
      suggest more complex mechanisms of lesion evolution beyond an isolated
      endothelial immune reaction and subsequent hypoxic tissue damage. The
      characteristic lesion morphology assists in differentiating the diagnosis of
      acute visual loss in neuroinflammatory disease. Specificity of the identified
      changes has to be determined in future studies also including patients with other
      retinal vascular diseases.

PMID- 26200514
TI  - MICROBIAL SPECTRUM AND OUTCOMES OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION
      VERSUS PARS PLANA VITRECTOMY.
AB  - PURPOSE: To compare infectious organisms and visual outcomes of endophthalmitis
      after intravitreal injection (IVI) with endophthalmitis after pars plana
      vitrectomy (PPV). METHODS: Retrospective, comparative, consecutive case series of
      patients diagnosed with presumed infectious endophthalmitis after IVI of an anti
      vascular endothelial growth factor medication or PPV between January 1, 2009, and
      October 1, 2012, from one center. Main outcome measures were infectious organism
      and final visual acuity. RESULTS: Forty-four cases of presumed infectious
      endophthalmitis (17 culture positive) occurred after IVI and 19 cases (9 culture
      positive) occurred after PPV. Of note, 56.3% of culture-positive IVI cases were
      due to bacteria associated with oral flora, primarily Streptococcus species,
      compared with none in the PPV group (P = 0.01). There was a trend approaching
      significance for IVI patients to have lost >=3 lines of visual acuity compared
      with PPV patients at final follow-up (P = 0.07). Within the IVI group, patients
      were more likely to have lost >=6 lines of visual acuity at final follow-up when
      endophthalmitis was due to an organism associated with oral flora (P = 0.007).
      CONCLUSION: Endophthalmitis after IVI has a higher likelihood of being due to
      oral flora compared with endophthalmitis after PPV. Among IVI patients, worse
      visual outcomes occurred when endophthalmitis was due to oral flora.

PMID- 26200515
TI  - PERIPHERAL RETINAL DEGENERATIONS AND RHEGMATOGENOUS DETACHMENT IN PRIMARY
      CONGENITAL GLAUCOMA.
AB  - BACKGROUND: To determine the prevalence of peripheral retinal degenerations (PRD)
      and rhegmatogenous retinal detachment in patients with primary congenital
      glaucoma (PCG). METHODS: Records of all patients with PCG operated from year 2000
      onwards were evaluated to look for the prevalence of rhegmatogenous retinal
      detachment. Of these, those children who were old enough to cooperate and had
      sufficient medial clarity were screened with an indirect ophthalmoscopy in a
      cross-sectional evaluation from 2010 to 2014. Peripheral retina was examined, and
      prevalence of PRD was estimated in this subset. For statistical purposes, only
      one eye of each patient was considered in this cross-sectional analysis. RESULTS:
      Of the 310 eyes (180 patients with PCG) operated from the year 2000 onwards, a
      rhegmatogenous retinal detachment was noted in 13 eyes (4%). Mean axial length of
      these eyes was 26.3 +/- 3.2 mm (range, 19.8-34.7 mm). Among the eyes screened for
      PRD (n = 60), prevalence of pathologic PRD (lattices with/without atrophic holes
      and isolated holes/tears) was 15%. The average follow-up between glaucoma
      filtering surgery and the date of last examination was 8.55 +/- 3.98 years
      (range, 5-20 years) in this subset. Mean axial length was significantly greater
      in eyes with pathologic PRD than in those without (28.1 +/- 3.3 mm vs. 25.8 +/-
      2.6 mm; P = 0.01). For axial length >= 26 mm, the odds of having a pathologic PRD
      were 14.4 times more than those with axial length < 26 mm (P < 0.001; 95%
      confidence interval, 1.7-120.5). CONCLUSION: Prevalence of PRD among eyes with
      PCG is high. Peripheral retinal screening should be performed in eyes with PCG,
      especially those with axial lengths >= 26 mm.

PMID- 26200516
TI  - HEADS-UP SURGERY FOR VITREORETINAL PROCEDURES: An Experimental and Clinical
      Study.
AB  - PURPOSE: To investigate the feasibility of performing vitrectomies while viewing
      a three-dimensional image on a large display in a heads-up position. METHODS:
      Twenty volunteers were compared performing meticulous tasks using the heads-up
      and the traditional method. Some optical parameters, resolution and depth of
      field, were measured, and the possibilities of digital image processing were
      investigated. In addition, routine use of the heads-up method for >400
      vitrectomies over 8 months was retrospectively analyzed. RESULTS: Of note, 91.7%
      of the volunteers preferred the ergonomics of the heads-up technique. The two
      methods were judged to be similar regarding speed and ease of microscopic
      manipulations and sharpness of image. Significantly fewer mistakes were made with
      the heads-up method. The measured resolution of the eyepieces was approximately
      twice that of the three-dimensional display, whereas depth of the field was about
      equal. Electronic amplification of the camera's signal resulted in increased
      image brightness, allowing use of reduced endoillumination levels. In clinical
      routine, better ergonomics, digital image processing, and use of a large display
      are found to be major advantages. CONCLUSION: The heads-up method is well suited
      for vitreoretinal surgery. With further technical improvements, the procedure
      should soon find widespread use.

PMID- 26200517
TI  - Vitrectomy With Intrasurgical Control of Ocular Hypotony as a Treatment for
      Central Retina Artery Occlusion.

PMID- 26200518
TI  - Ureteral implantation using a three-stitch ureteroneocystostomy: description of
      technique and outcome in nine dogs.
AB  - OBJECTIVE: To report the procedure, postoperative outcome and complications of a
      new technique for ureteral implantation by means of a three-stitch
      ureteroneocystostomy in dogs. MATERIALS AND METHODS: Clinical records of dogs
      requiring ureteral implantation between April 2007 and June 2013 were
      retrospectively reviewed. Data retrieved included signalment, preoperative
      biochemistry results, details of the surgical procedure, perioperative and
      postoperative complications, postoperative biochemistry results and outcome.
      RESULTS: Nine dogs fulfilled the inclusion criteria. Follow-up times ranged from
      10 to 79 months (median 30 months), with 8 of 9 dogs having an excellent long
      term outcome and no major postoperative complications. One dog with follicular
      cystitis as a comorbidity developed obstruction from inflammatory granuloma and
      required revision surgery. CLINICAL SIGNIFICANCE: The three-stitch technique for
      ureteral implantation compares favourably to previously documented techniques in
      terms of outcome and complication rates. Reduced tissue handling and a decreased
      volume of suture material may be beneficial for healing. The technique is also
      faster than previously described options, which may be of benefit in unstable
      patients requiring ureteral implantation due to traumatic injury or rupture.

PMID- 26200519
TI  - Dimensional error of three-dimensional images generated by different software.
AB  - The aim of this study was to evaluate the accuracy of three-dimensional (3D)
      reconstructions generated by different software, computed tomography (CT)
      scanners and slice thicknesses. Ten human dry mandibles were scanned by CT and
      cone beam CT (CBCT). Digital files were processed in different software systems
      and 3D reconstructions were performed. Linear measures were made and compared.
      The results showed significant differences in linear distances between the human
      dry mandibles and their 3D reconstructions. The relative error from CBCT images
      ranged from 3.10 to 4.82% and from 3.40 to 5.92% in CT images. It is important to
      consider that the performance of the software is not just related to the
      algorithm used, but mostly with its handling, that can facilitate or not the
      measurement by the operator. In conclusion, the discrepancies were not greater
      than 0.58 mm, so they should not affect the image quality.

PMID- 26200521
TI  - A retrospective analysis of complications observed in children with acute
      lymphoblastic leukemia during chemotherapy.
AB  - BACKGROUND: We aimed to evaluate the complications that we observed in children
      with acute lymphoblastic leukemia (ALL) during the remission induction,
      consolidation, and reinduction phases of chemotherapy retrospectively. METHODS:
      We analysed the clinical records of 128 patients with ALL who were diagnosed and
      treated in the Department of Pediatric Hematology of Istanbul Medeniyet
      University Goztepe Training Hospital between August 2009 and April 2014 to
      document the acute complication other than febrile neutropenia episodes, which
      developed during the induction, consolidation and reinduction phases of
      chemotherapy. RESULTS: We documented 279 complications. Of these, 53.05% were in
      males, 46.95% in females; 32.26% were in standard-risk, 45.52% in medium-risk,
      22.22% in high-risk group of patients. Common documented events were pneumonia
      (25%), therapy-induced hyperglycemia (16.40%) therapy-related hepatitis (15.6%),
      generalized tonic-clonic seizures (14.8%), anaphylaxis to asparaginase (14.1%),
      hypertension (13.3%) varicella zoster virus (VZV) infection (13.3%), renal
      tubulopathy (12.5%). Time of complications was induction phase in 32.62%,
      consolidation in 19.35%, HR blocks in 18.28%, reinduction 29.75% during the
      phases. Mortality rate due to complications was 13.28%. CONCLUSIONS: Therapy
      related complications can limit the survival rates in children with ALL. To
      minimize the treatment burden, even very rare complications must be considered
      and treated promptly with a multidisciplinary approach.

PMID- 26200522
TI  - Comparison of ferrous sulfate, polymaltose complex and iron-zinc in iron
      deficiency anemia.
AB  - AIM: The purpose of this study was to compare the effectiveness of different oral
      iron preparations in children with iron deficiency anemia (IDA). METHODS: Sixty
      children with IDA, aged between 6 months and 180 months, were randomly assigned
      into three treatment groups. Group I included children with IDA who received
      ferrous sulfate (Fe-S); Group II included children receiving iron polymaltose
      complexes (Fe-OH-PM), and Group III included children receiving a single
      preparation of combined iron and zinc (Fe-Zn). The effect of different iron
      preparations were evaluated and compared. The duration of treatment was 8 weeks.
      Hemoglobin (Hgb) levels, as well as other hematological parameters were
      determined at admission and the first, fourth, and eighth weeks of the treatment.
      RESULTS: The Hgb levels of patients in all three groups were statistically higher
      in the fourth (p=0.001) and eighth (p<0.001) weeks compared to baseline; although
      there was no difference between the groups at the end of the treatment period (p
      >0.05). CONCLUSION: Our results indicate that, Fe-OH-PM and Fe-Zn preparations
      may also be preferred as a choice like Fe-S for treatment of children with IDA.

PMID- 26200520
TI  - Association Between Sleep and Physical Function in Older Veterans in an Adult Day
      Healthcare Program.
AB  - OBJECTIVES: To examine whether sleep disturbance is associated with poor physical
      function in older veterans in an adult day healthcare (ADHC) program. DESIGN:
      Cross-sectional. SETTING: One ADHC program in a Veterans Affairs Ambulatory Care
      Center. PARTICIPANTS: Older veterans (N = 50) enrolled in a randomized controlled
      trial of a sleep intervention program who had complete baseline data.
      MEASUREMENTS: Information on participant characteristics (e.g., age, depression,
      relationship to caregiver, pain, comorbidity) was collected using appropriate
      questionnaires. Physical function was measured using activity of daily living
      (ADL) and instrumental ADL (IADL) total scores from the Older Americans Resources
      and Services Multidimensional Functional Assessment Questionnaire. Sleep was
      assessed subjectively (Pittsburgh Sleep Quality Index, Insomnia Severity Index)
      and objectively (wrist actigraphy). RESULTS: Participants required substantial
      assistance with ADLs and IADLs. A regression model showed that participant
      characteristics (marital status, use of sleep medication, comorbidity,
      posttraumatic stress disorder) and living arrangement (living with a spouse or
      others) were significantly associated with poor physical function. Poorer
      objective sleep (total sleep time, total numbers of awakenings, total wake time)
      was significantly associated with poor physical function, accounting for a
      significant proportion of the variance other than participant characteristics.
      CONCLUSION: Objective measures of nighttime sleep disturbance were associated
      with poor physical function in older veterans in an ADHC program. Further
      research is needed to determine whether interventions to improve sleep will delay
      functional decline in this vulnerable population.

PMID- 26200523
TI  - Disease severity and quality of life in children with atopic dermatitis: PO
      SCORAD in clinical practice.
AB  - BACKGORUND: Atopic dermatitis (AD) can significantly compromise the quality of
      life (QoL). The aim of our investigation was to evaluate whether QoL correlates
      with AD severity, evaluated through the physician and the patient perspective, in
      a sample of Italian children. METHODS: Forty children with AD were evaluated.
      Disease severity was assessed by the physician and the patients (or their
      parents) using the SCORAD and the patient-oriented SCORAD (PO-SCORAD) tools,
      respectively. Patients or their parents completed specific QoL questionnaires
      (IDQOL/CDLQI). Spearman's correlation coefficient and non-parametric analysis of
      covariance were used to analyze the data. RESULTS: SCORAD e PO-SCORAD were
      moderately but significantly correlated (rho Spearman=0.55, P<0.01). QoL scores
      ranged from 1 to 23, with a median score of 4.0 (higher scores represent more
      impaired QoL). After adjustment for age and sex, children with SCORAD>40 had
      significantly higher QoL scores (more impaired QoL) than those with SCORAD<=40
      (median QoL of 5 and 4, respectively, P=0.048). Even higher differences emerged
      when AD severity was self-assessed (median QoL of 6 and 3.5 for children with PO
      SCORAD>40 and PO-SCORAD<=40, respectively, P=0.01). AD children with concomitant
      food allergy had a significantly more impaired QoL than those with AD only
      (P=0.040). No significant difference in QoL was observed according to sex or age.
      CONCLUSIONS: In our sample of AD children, QoL appeared slightly-moderately
      altered, and increasing disease severity was associated with greater impairment
      in QoL. SCORAD and PO-SCORAD were fairly correlated and the association of QoL
      was somewhat stronger with the PO-SCORAD than the SCORAD Index. This supports the
      usefulness of PO-SCORAD for the self-assessment of AD in children, and suggests
      the importance to integrate physician and patient perspectives in the management
      of AD.

PMID- 26200524
TI  - A new improved protocol for in vitro intratubular dentinal bacterial
      contamination for antimicrobial endodontic tests: standardization and validation
      by confocal laser scanning microscopy.
AB  - OBJECTIVES: To compare three methods of intratubular contamination that simulate
      endodontic infections using confocal laser scanning microscopy (CLSM). MATERIAL
      AND METHODS: Two pre-existing models of dentinal contamination were used to
      induce intratubular infection (groups A and B). These methods were modified in an
      attempt to improve the model (group C). Among the modifications it may be
      included: specimen contamination for five days, ultrasonic bath with BHI broth
      after specimen sterilization, use of E. faecalisduring the exponential growth
      phase, greater concentration of inoculum, and two cycles of centrifugation on
      alternate days with changes of culture media. All specimens were longitudinally
      sectioned and stained with of LIVE/DEAD for 20 min. Specimens were assessed using
      CLSM, which provided images of the depth of viable bacterial proliferation inside
      the dentinal tubules. Additionally, three examiners used scores to classify the
      CLSM images according to the following parameters: homogeneity, density, and
      depth of the bacterial contamination inside the dentinal tubules. Kruskal-Wallis
      and Dunn's tests were used to evaluate the live and dead cells rates, and the
      scores obtained. RESULTS: The contamination scores revealed higher contamination
      levels in group C when compared with groups A and B (p<0.05). No differences were
      observed between group A and B (p>0.05). The volume of live cells in group C was
      higher than in groups A and B (p<0.05). CONCLUSION: The new protocol for
      intratubular infection resulted in high and uniform patterns of bacterial
      contamination and higher cell viability in all specimens when compared with the
      current methods.

PMID- 26200525
TI  - Efficacy of ultrasonic activation of NaOCl and orange oil in removing filling
      material from mesial canals of mandibular molars with and without isthmus.
AB  - OBJECTIVES: The aim of this study was to evaluate the volume of remaining filling
      material after passive ultrasonic irrigation (PUI) of sodium hypochlorite (NaOCl)
      and orange oil in mesial canals of mandibular molars, with and without isthmus.
      MATERIAL AND METHODS: Thirty mesial roots of mandibular molars were divided
      according to the presence or absence of isthmus. Canals were prepared and filled
      (Micro-CT #1). Filling was removed using rotary instruments, and specimens were
      sub-divided into three groups according to the irrigation procedures:
      Conventional - conventional irrigation with NaOCl, PUI/NaOCl - PUI of NaOCl
      (three activations, 20 seconds each), and PUI/orange oil - PUI of orange oil
      (Micro-CT#2). Specimens were enlarged using the X2 and X3 ProTaper Next
      instruments and submitted to the same irrigation protocols (Micro-CT #3).
      RESULTS: No differences were found between the experimental groups in each stage
      of assessment (P>0.05). The volume of residual filling material was similar to
      that in Micro-CT #2 and Micro-CT #3, but lower than that observed in Micro-CT #1
      (P<0.05). When groups were pooled according to the presence or absence of an
      isthmus, volume of residual filling material was higher in specimens presenting
      isthmus (P<0.05). CONCLUSIONS: PUI of NaOCl or orange oil did not improve filling
      removal. Isthmus consists in an anatomical obstacle that impairs the removal of
      filling material.

PMID- 26200526
TI  - Management of painful temporomandibular joint clicking with different intraoral
      devices and counseling: a controlled study.
AB  - OBJECTIVE: The benefit of the use of some intraoral devices in arthrogenous
      temporomandibular disorders (TMD) patients is still unknown. This study assessed
      the effectiveness of the partial use of intraoral devices and counseling in the
      management of patients with disc displacement with reduction (DDWR) and
      arthralgia. MATERIALS AND METHODS: A total of 60 DDWR and arthralgia patients
      were randomly divided into three groups: group I (n=20) wore anterior
      repositioning occlusal splints (ARS); group II (n=20) wore the Nociceptive
      Trigeminal Inhibition Clenching Suppression System devices (NTI-tss); and group
      III (n=20) only received counseling for behavioral changes and self-care (the
      control group). The first two groups also received counseling. Follow-ups were
      performed after 2 weeks, 6 weeks and 3 months. In these sessions, patients were
      evaluated by means of a visual analogue scale, pressure pain threshold (PPT) of
      the temporomandibular joint (TMJ), maximum range of motion and TMJ sounds.
      Possible adverse effects were also recorded, such as discomfort while using the
      device and occlusal changes. The results were analyzed with ANOVA, Tukey's and
      Fisher Exact Test, with a significance level of 5%. RESULTS: Groups I and II
      showed improvement in pain intensity at the first follow-up. This progress was
      recorded only after 3 months in Group III. Group II showed an increased in joint
      sounds frequency. The PPT values, mandibular range of motion and the number of
      occlusal contacts did not change significantly. CONCLUSION: The simultaneous use
      of intraoral devices (partial time) plus behavioral modifications seems to
      produce a more rapid pain improvement in patients with painful DDWR. The use of
      NTI-tss could increase TMJ sounds. Although intraoral devices with additional
      counseling should be considered for the management of painful DDWR, dentists
      should be aware of the possible side effects of the intraoral device's design.

PMID- 26200527
TI  - Analysis of the reaction of subcutaneous tissues in rats and the antimicrobial
      activity of calcium hydroxide paste used in association with different
      substances.
AB  - The aim of this study was to evaluate the subcutaneous tissue response in rats
      and the antimicrobial activity of intracanal calcium hydroxide dressings mixed
      with different substances against E. faecalis. Fifty four rats were divided into
      three experimental groups according to the vehicle in the calcium hydroxide
      treatment: 0.4% chlorohexidine in propylene glycol (PG),Casearia sylvestris Sw in
      PG and calcium hydroxide+PG (control group). The pastes were placed into
      polyethylene tubes and implanted into the subcutaneous tissue. After 7, 14 and 30
      days, the samples were processed and histologically evaluated (hematoxylin and
      eosin). The tissue surface in contact with the material was analyzed, and the
      quantitative analysis determined the volume density occupied by the inflammatory
      infiltrate (giant cells, polymorphonuclear cells and mononuclear cells),
      fibroblasts, collagen fibers and blood vessels. For the antimicrobial analysis,
      20 dentin blocks infected with E. faecalis were treated with calcium hydroxide
      pastes in different vehicles; 0.4% chlorhexidine in PG, PG, extract from Casearia
      sylvestris Sw in PG and a positive control (infection and without medication) for
      7 days. The efficiency of the pastes was evaluated by the live/dead technique and
      confocal microscopy. The results showed that 0.4% chlorhexidine induced a higher
      inflammatory response than the other groups. The Casearia sylvestris Sw extract
      showed satisfactory results in relation to the intensity of the inflammatory
      response. In the microbiological test, there were no statistical differences
      between the evaluated intracanal dressings and the percentage of bacterial
      viability was between 33 and 42%. The control group showed an 86% viability.
      Antimicrobial components such as chlorhexidine or Casearia sylvestris Sw did not
      improve the antimicrobial activity against E. faecalis in comparison to the
      calcium hydroxide+PG treatment. In addition, the incorporation of chlorhexidine
      in the calcium hydroxide paste promoted the highest inflammatory response.

PMID- 26200528
TI  - Planarian 'kidneys' go with the flow.
AB  - Flatworms have organs called protonephridia that could be used as a model system
      for the study of kidney disease. 

PMID- 26200529
TI  - Correction to Multiplex Microfluidic Paper-based Immunoassay for the Diagnosis of
      Hepatitis C Virus Infection.

PMID- 26200531
TI  - Editorial in this issue - Bladder Neck Reconstruction in Radical Prostatectomy:
      What we still can learn and improve?

PMID- 26200530
TI  - Efficacy of antibiotic prophylaxis in cystoscopy to prevent urinary tract
      infection: a systematic review and meta-analysis.
AB  - OBJECTIVE: To estimate the efficacy of antibiotic prophylaxis to prevent urinary
      tract infection in patients (both gender) who undergo a cystoscopy with sterile
      urine. MATERIALS AND METHODS: Search strategy (January 1980-December 2013) in
      Medline via PubMed, CENTRAL, and EMBASE. Additionally, we searched databases for
      registered trials and conference abstracts, as well as reference lists of
      systematic reviews and included studies. Seven published randomized clinical
      trials (January 1, 1980 to December 31, 2013) were included in quantitative
      analyses with no language restrictions. Two independent reviewers collected data.
      Risk of bias was evaluated with the Cochrane Collaboration tool. We performed a
      fixed effect analyses due to statistical homogeneity. The primary outcome was
      urinary tract infection and the secondary was asymptomatic bacteriuria. The
      effect measure was the risk difference (RD) with 95% confidence interval. The
      planned interventions were: Antibiotic vs placebo; Antibiotic vs no intervention
      and Antibiotic vs any other intervention. RESULTS: 3038 patients were found in
      seven studies. For the primary outcome, we included 5 studies and we found a RR
      0.53 CI95% (0.31, 0.90) and a RD-0.012 CI95% (-0.023,-0.002), favoring antibiotic
      prophylaxis. For asymptomatic bacteriuria we included 6 studies and we found a RR
      0.28 CI95% (0.20, 0.39) and a RD-0.055 CI95% (-0.07,-0.039), was found favoring
      prophylaxis. According to GRADE evaluation, we considered moderate quality of
      evidence for both outcomes. The subgroup analysis showed that only two studies
      were classified as having low risk of bias: Cam 2009 and Garcia-Perdomo 2013.
      They showed no statistical differences (RD-0.009 CI95% -0.03, 0.011).
      CONCLUSIONS: Based on studies classified as low risk of bias, we found moderate
      evidence to not recommend the use of antibiotic prophylaxis to prevent urinary
      tract infection and asymptomatic bacteriuria in patients who undergo cystoscopy
      with sterile urine in an ambulatory setting.

PMID- 26200532
TI  - Editor's Comment - Best videos of the year for the International Brazilian
      Journal of Urology 2014.

PMID- 26200533
TI  - Difference of opinion - Inflatable Penile Prosthesis - Opinion: Why I prefer the
      infrapubic access.

PMID- 26200534
TI  - Difference of opinion - Inflatable Penile Prosthesis - Opinion: Why I prefer the
      penoscrotal access.

PMID- 26200535
TI  - Optimal duration of androgen deprivation therapy following radiation therapy in
      intermediate- or high-risk nonmetastatic prostate cancer: A systematic review and
      metaanalysis.
AB  - OBJECTIVES: To investigate current evidence on the optimal duration of adjuvant
      hormone deprivation for prostate cancer treated with radiation therapy with
      curative intent. MATERIALS AND METHODS: A systematic search was performed in
      electronic databases. Data from randomized trials comparing different durations
      of hormone blockade was collected for pooled analysis. Overall survival, disease
      free survival, disease-specific survival and toxicity were the outcomes of
      interest. Meta-analyses were performed using random-effects model. RESULTS: Six
      studies met the eligibility criteria. For overall survival, the pooled data from
      the studies demonstrated a statistically significant benefit for longer hormone
      deprivation (Hazard Ratio 0.84; 95% CI 0.74 - 0.96). A statistically significant
      benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 
      0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 - 0.85).
      Studies with longer blockade duration arm demonstrated greater benefit. Toxicity
      was low, with no increase in cardiovascular events. CONCLUSIONS: Longer duration
      of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in
      patients with intermediate and high-risk non-metastatic prostate cancer. However,
      this evidence is based on trials using older radiation techniques, and further
      research of combination of androgen deprivation and new RT technologies may be
      warranted.

PMID- 26200537
TI  - Prostate cancer volume estimations based on transrectal ultrasonography-guided
      biopsy in order to predict clinically significant prostate cancer.
AB  - INTRODUCTION: Tumor diameter is a reliable parameter to estimate tumor volume in
      solid organ cancers; its use in prostate cancer is controversial since it
      exhibits a more irregular pattern of growth. This study aimed to examine the
      association between the tumor volume estimations based on transrectal ultrasound
      (TRUS) guided biopsy results and the tumor volume measured on the pathological
      specimen. MATERIALS AND METHODS: A total of 237 patients who underwent radical
      retropubic prostatectomy (RRP) were included in this retrospective study. The
      differences and correlations between cancer volume estimations based on TRUS
      guided biopsy findings and cancer volume estimations based on post-prostatectomy
      pathology specimens were examined. In addition, diagnostic value of TRUS guided
      biopsy-based volume estimations in order to predict clinically significant cancer
      (>0.5 cc) were calculated. RESULTS: The mean cancer volume estimated using TRUS
      biopsy results was lower (5.5+/-6.5 cc) than the mean cancer volume calculated
      using prostatectomy specimens (6.4+/-7.6 cc) (p<0.041).TRUS guided biopsy
      examination resulted in 5 false positive and 15 false negative cases. There was a
      significant but weak correlation between the two parameters (r=0.62, p<0.001).
      The sensitivity and specificity of TRUS guided biopsy in predicting the presence
      of clinically significant cancer was 93.4% (95% CI, 89.1-96.1) and 50.0% (95% CI,
      20.1-79.9), respectively. CONCLUSIONS: TRUS guided biopsy-derived estimations
      seem to have a limited value to predict pathologically established tumor volume.
      Further studies are warranted to identify additional methods that may more
      accurately predict actual pathological characteristics and prognosis of prostate
      cancer.

PMID- 26200536
TI  - Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity
      with high-dose-rate brachytherapy for large prostate volumes.
AB  - PURPOSE: To evaluate dosimetric coverage of the prostate, normal tissue sparing,
      and acute toxicity with HDR brachytherapy for large prostate volumes. MATERIALS
      AND METHODS: One hundred and two prostate cancer patients with prostate volumes
      >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy +/-
      intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions
      between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350
      1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses
      consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%)
      unfavorable intermediate risk, high risk, and very high risk patients received
      androgen deprivation therapy. Acute toxicity was graded according to the Common
      Terminology Criteria for Adverse Events (CTCAE) version 4. RESULTS: Median follow
      up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of
      102 (3%) patients developed Grade 2 acute proctitis. No variables were
      significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%)
      patients developed Grade 2 acute urinary retention. American Urological
      Association (AUA) symptom score was the only variable significantly associated
      with Grade 2 acute urinary retention (p=0.04). There was no >= Grade 3 acute
      toxicity. CONCLUSIONS: Dosimetric coverage of the prostate and normal tissue
      sparing were adequate in patients with prostate volumes >50 mL. Higher pre
      treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary
      retention. However, the overall incidence of acute toxicity was acceptable in
      patients with large prostate volumes.

PMID- 26200538
TI  - Probability of extraprostatic disease according to the percentage of positive
      biopsy cores in clinically localized prostate cancer.
AB  - OBJECTIVE: Prediction of extraprostatic disease in clinically localized prostate
      cancer is relevant for treatment planning of the disease. The purpose of this
      study was to explore the usefulness of the percentage of positive biopsy cores to
      predict the chance of extraprostatic cancer. MATERIALS AND METHODS: We evaluated
      1787 patients with localized prostate cancer submitted to radical prostatectomy.
      The percentage of positive cores in prostate biopsy was correlated with the
      pathologic outcome of the surgical specimen. In the final analysis, a correlation
      was made between categorical ranges of positive cores (10% intervals) and the
      risk of extraprostatic extension and/or bladder neck invasion, seminal vesicles
      involvement or metastasis to iliac lymph nodes. Student's t test was used for
      statistical analysis. RESULTS: For each 10% of positive cores we observed a
      progressive higher prevalence of extraprostatic disease. The risk of cancer
      beyond the prostate capsule for <10% positive biopsy cores was 7.4% and it
      increased to 76.2% at the category 90-100% positive cores. In patients with
      Gleason grade 4 or 5, the risk of extraprostatic cancer prostate was higher than
      in those without any component 4 or 5. CONCLUSION: The percentage of positive
      cores in prostate biopsy can predict the risk of cancer outside the prostate. Our
      study shows that the percentage of positive prostate biopsy fragments helps
      predict the chance of extraprostatic cancer and may have a relevant role in the
      patient's management.

PMID- 26200539
TI  - Anesthesiologic effects of transperitoneal versus extraperitoneal approach during
      robot-assisted radical prostatectomy: results of a prospective randomized study.
AB  - OBJECTIVES: To compare the effects of CO(2) insufflation on hemodynamics and
      oxygen levels and on acid-base level during Robot-Assisted Radical Prostatectomy
      (RARP) with transperitoneal (TP) versus extra-peritoneal (EP) accesses. MATERIALS
      AND METHODS: Sixty-two patients were randomly assigned to TP (32) and EP (30) to
      RARP. Pre-operation data were collected for all patients. Hemodynamic,
      respiratory and blood acid-base parameters were measured at the moment of
      induction of anesthesia (T0), after starting CO(2) insufflation (T1), and at 60
      (T2) and 120 minutes (T3) after insufflation. In all cases, the abdominal
      pressure was set at 15 mmHg. Complications were reported according to the Clavien
      Dindo classification. Student's two-t-test, with a significance level set at
      p<0.05, was used to compare categorical values between groups. The Mann-Whitney U
      test was used to compare the median values of two nonparametric continuous
      variables. RESULTS: The demographic characteristics of the patients in both
      groups were statistically comparable. Analysis of intra-operative anesthesiologic
      parameters showed that partial CO(2) pressure during EP was significantly higher
      than during TP, with a consequent decrease in arterial pH. Other parameters
      analysed were similar in the two groups. Postoperative complications were
      comparable between groups. The most important limitations of this study were the
      small size of the patient groups and the impossibility of maintaining standard
      abdominal pressure throughout the operational phases, despite attempts to
      regulate it. CONCLUSIONS: This prospective randomized study demonstrates that,
      from the anesthesiologic viewpoint, during RARP the TP approach is preferable to
      EP, because of lower CO(2) reabsorption and risk of acidosis.

PMID- 26200540
TI  - Utilization and perioperative complications of laparoscopic cryoablation vs.
      robotic partial nephrectomy for localized renal tumors.
AB  - OBJECTIVE: To compare the utilization, perioperative complications and predictors
      of LCA versus RPN in the treatment of localized renal tumors. METHODS: From the
      Nationwide Inpatient Sample we identified patients undergoing RPN or LCA for the
      treatment of localized renal tumors from October 2008 through 2010. Patient and
      hospital-specific factors which predict postoperative complications and use of
      LCA were investigated. RESULTS: 14,275 patients with localized renal tumors were
      identified: 70.3% had RPN and 29.7% had LCA. LCA was more common in older patient
      and at hospitals without robotic consoles. No difference was identified in
      perioperative complications (0.2% vs. 0.2%), transfusion (5.1% vs. 6.2%), length
      of stay (2.9 vs. 3.0 days) or median cost ($41,753 vs. $44,618) between the
      groups, LCA vs. RPN. On multivariate analysis sicker patients were more likely to
      have LCA (OR 1.34, p=0.048) and sicker patients had greater postoperative
      complications (OR 3.30, p<0.001); LCA did not predict more complications (OR
      1.63, p=0.138) and LCA was performed at hospitals without RCs (OR 0.02, p<0.001).
      Limitations include observational study design, inability to assess disease
      severity, operative time, or body mass index, which may affect patient selection
      and outcomes. CONCLUSIONS: More patients had RPN vs. LCA; surgical technique was
      not predictive of postoperative complications. As technology develops to treat
      localized renal tumors, it will be important to continue to track outcomes and
      costs for procedures including RPN and LCA.

PMID- 26200541
TI  - Feasibility, complications and oncologic results of a limited inguinal lymph node
      dissection in the management of penile cancer.
AB  - PURPOSE: In patients with penile cancer (PeCa) and increased risk of inguinal
      lymphatic dissemination, inguinal lymphadenectomy offers a direct histological
      staging as the most reliable tool for assessment of the nodal metastasic status
      and a definitive oncologic treatment simultaneously. However, peri- and/or
      postoperative mutilating sequalae often occurn. We report on clinical outcome and
      complications of a limited inguinal lymph node (LN) dissection. MATERIALS AND
      METHODS: Clinical and histopathological data of all patients with PeCa who
      underwent limited inguinal lymphadenectomy (LIL) at our institution between 1986
      and 2012 were comprehensively analyzed. Perioperative results were presented in
      relation to one-sided procedures, if appropriate, which were assessed without
      cross comparison with contralateral LILs. RESULTS: 29 consecutive patients with
      PeCa aged 60+/-10.3 years were included in the current study with 57 one-sided
      LIL performed. Mean operative time for one-sided LIL was 89.0+/-37.3 minutes with
      8.1+/-3.7 LNs removed. A complication rate of 54.4% (n=31), including 16 minor
      and 15 major complications was found in a total of 57 procedures with leg oedema
      being the most prevalent morbidity (15.8%). 4 patients with clinically positive
      LNs developed inguinal lymphatic recurrence within 9 months after surgery.
      CONCLUSIONS: Our technique of limited inguinal LN dissection provided an
      acceptable complication rate without aggravating morbidity. We experienced no
      recurrences in clinically LN negative patients, so that the approach might be a
      reasonable option in this scenario. In patients with enlarged LNs, radical
      inguinal lymphadenectomy still appears to represent the gold standard.

PMID- 26200542
TI  - Percutaneous nephrolithotomy in patients with solitary kidney: a critical outcome
      analysis.
AB  - PURPOSE: To describe our experience with percutaneous nephrolithotomy (PCNL) in
      patients with solitary kidneys and analyze factors that can impact on intra
      operative bleeding and postoperative complications. MATERIALS AND METHODS: We
      reviewed our stone database searching for patients with solitary kidney who
      underwent PCNL from Jan-05 through Oct-13. Demographic data, stone
      characteristics, and intra- and postoperative outcomes were recorded. Spearman
      correlation was performed to assess which variables could impact on bleeding and
      surgical complications. Linear and logistic regressions were also performed.
      RESULTS: Twenty-seven patients were enrolled in this study. The mean age and BMI
      were 45.6 years and 28.8Kg/m(2), respectively; 45% of cases were classified as
      Guys 3 (partial staghorn or multiple stones) or 4 (complete staghorn) - complex
      cases. Stone-free rate was 67%. Eight (29.6%) patients had postoperative
      complications (five of them were Clavien 2 and three were Clavien 3). On
      univariate analysis only number of tracts was associated with increased bleeding
      (p=0.033) and only operative time was associated with a higher complication rate
      (p=0.044). Linear regression confirmed number of access tracts as significantly
      related to bleeding (6.3, 95%CI 2.2-10.4; p=0.005), whereas logistic regression
      showed no correlation between variables in study and complications. CONCLUSIONS:
      PCNL in solitary kidneys provides a good stone-free rate with a low rate of
      significant complications. Multiple access tracts are associated with increased
      bleeding.

PMID- 26200543
TI  - Studying inhibition of calcium oxalate stone formation: an in vitro approach for
      screening hydrogen sulfide and its metabolites.
AB  - PURPOSE: Calcium oxalate urolithiasis is one of the most common urinary tract
      diseases and is of high prevalence. The present study proposes to evaluate the
      antilithiatic property of hydrogen sulfide and its metabolites like thiosulfate &
      sulfate in an in vitro model. MATERIALS AND METHODS: The antilithiatic activity
      of sodium hydrogen sulfide (NaSH), sodium thiosulfate (Na(2)S(2)O(3)) and sodium
      sulfate (Na(2)SO(4)) on the kinetics of calcium oxalate crystal formation was
      investigated both in physiological buffer and in urine from normal and recurrent
      stone forming volunteers. The stones were characterized by optical and
      spectroscopic techniques. RESULTS: The stones were characterized to be
      monoclinic, prismatic and bipyramidal habit which is of calcium monohydrate and
      dihydrate nature. The FTIR displayed fingerprint corresponding to calcium oxalate
      in the control while in NaSH treated, S=O vibrations were visible in the
      spectrum. The order of percentage inhibition was NaSH>Na(2)S(2)O(3)>Na(2)SO(4).
      CONCLUSION: Our study indicates that sodium hydrogen sulfide and its metabolite
      thiosulfate are inhibitors of calcium oxalate stone agglomeration which makes
      them unstable both in physiological buffer and in urine. This effect is
      attributed to pH changes and complexing of calcium by S(2)O(3)(2)-and SO(4)(2)-
      moiety produced by the test compounds.

PMID- 26200544
TI  - Antilithiatic Activity of phlorotannin rich extract of Sarghassum Wightii on
      Calcium Oxalate Urolithiais - InVitro and In Vivo Evaluation.
AB  - PURPOSE: Urolithiasis is a common urological disorder responsible for serious
      human affliction and cost to the society with a high recurrence rate. The aim of
      the present study was to systematically evaluate the phlorotannin rich extract of
      Sargassum wightii using suitable in vitro and in vivo models to provide
      scientific evidence for its antilithiatic activity. MATERIALS AND METHODS: To
      explore the effect of Sargassum wightii on calcium oxalate crystallization, in
      vitro assays like crystal nucleation, aggregation and crystal growth were
      performed. Calcium oxalate urolithiasis was induced in male Sprague dawley rats
      using a combination of gentamicin and calculi producing diet (5% ammonium oxalate
      and rat pellet feed). The biochemical parameters like calcium, oxalate,
      magnesium, phosphate, sodium and potassium were evaluated in urine, serum and
      kidney homogenates. Histopathological studies were also done to confirm the
      biochemical findings. RESULTS: The yield of Sargassum wightii extract was found
      to be 74.5 gm/kg and confirmed by quantitative analysis. In vitro experiments
      with Sargassum wightii showed concentration dependent inhibition of calcium
      oxalate nucleation, aggregation and growth supported by SEM analysis. In the in
      vivo model, Sargassum wightii reduced both calcium and oxalate supersaturation in
      urine, serum and deposition in the kidney. The biochemical results were supported
      by histopathological studies. CONCLUSION: The findings of the present study
      suggest that Sargassum wightii has the ability to prevent nucleation, aggregation
      and growth of calcium oxalate crystals. Sargassum wightii has better preventive
      effect on calcium oxalate stone formation indicating its strong potential to
      develop as a therapeutic option to prevent recurrence of urolithiasis.

PMID- 26200545
TI  - Flowmetry/ pelvic floor electromyographic findings in patients with detrusor
      overactivity.
AB  - To evaluate different flowmetry/EMG patterns in patients with proven detrusor
      overactivity (DO) and compare them with that of a group of patients with lower
      urinary tract symptoms (LUTS) but without DO. MATERIALS AND METHODS: We
      retrospectively evaluated the records of 100 patients with frequent urinary tract
      infection or any kind of storage or voiding symptoms that had undergone
      urodynamic testing: 50 cases with proven DO on cystometry who had a good quality
      flowmetry/EMG and 50 patients without DO. EMG lag time (the time distance between
      pelvic floor EMG inactivation and the start of urine flow) and different flow
      curve pattern were recorded and compared. RESULTS: The age and gender
      distribution were not statistically significant between the two groups. A
      negative lag time (<= 0 sec) and an obstructive pattern were the only parameters
      that were more commonly seen in the DO group. Sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of a lag times <2 sec
      for diagnosing DO were 70%, 96%, 96% and 72%, respectively. For a negative lag
      time, they were 52%, 100%, 100% and 63%, respectively. CONCLUSIONS: A lag time <2
      sec is a useful flowmetric finding that effectively rules out patients with LUTS
      that do not have DO (specificity and PPV=96%). With the cutoff of zero or less,
      specificity and PPV will be 100%. It has lower sensitivity and NPV, however, and
      is not measurable in a considerable population of patients with DO that have
      concomitant DV.

PMID- 26200546
TI  - Detrusor after-contraction: a new insight.
AB  - AIMS: Detrusor after-contractions (DAC) are non-common in adults. Both definition
      (nothing in ICS reports) and significance (artefact, link with detrusor
      overactivity (DO) or bladder outlet obstruction (BOO)) remain discussed. Our
      purpose was to carry out an analysis of the urodynamic parameters during voidings
      with DAC and, using the VBN model, to simulate pathophysiological conditions able
      to explain both voiding phase and DAC. MATERIALS AND METHODS: From large
      urodynamic database of patients referred for evaluation of lower urinary tract
      dysfunction, DAC were observed in 60 patients (5.7%). Criteria for DAC were post
      void residual <30mL and increase of detrusor pressure >10cmH(2)O. VBN model was
      used for analysis of both pressure and flow curves, and simulations of
      pathophysiological conditions. RESULTS: Onset of DAC (ODAC) occurred when Q=7.3+/
      5.7mL/s and bladder volume=17.9+/-15.4mL. Urgency-frequency syndrome and
      urodynamic diagnosis of DO were the more frequent scenarios associated with DAC.
      ODAC was associated to an inversion of the slope of detrusor pressure curve
      without any perturbation in flow curve. Among tested pathophysiological
      hypothesis (great, abnormal, detrusor force, sphincter contraction), none allowed
      restoring all recorded curves (flow rate, voiding pressure and DAC). CONCLUSION:
      No urodynamic characteristic of the first part of voiding is an index of
      occurrence of DAC. ODAC is a significant phenomenon linked with the bladder
      collapse. DAC is not associated with BOO but more probably with DO and appears as
      the result of local conditions in an almost empty bladder (concentration of
      stresses around a transducer); thus DAC seems of weak clinical significance.

PMID- 26200547
TI  - Patient and partner outcome of inflatable and semi-rigid penile prosthesis in a
      single institution.
AB  - INTRODUCTION: Penile prostheses are subject to a continuous development and have
      gained better mechanical reliability and safety during the last decades. In this
      study, we aimed to investigate the outcomes and satisfaction rates of inflatable
      penile prosthesis (IPP) and semirigid penile prosthesis (SPP) implantation.
      MATERIALS AND METHODS: From August 2001 to June 2012, 257 men with erectile
      dysfunction (ED) underwent penile prosthesis implantation (PPI) at our
      institution. Of the 257 patients, 118 underwent implantation of IPP and 139
      underwent SPP implantation. The pre-operative and post-operative erectile status
      of the patients were assessed by international index of erectile function (IIEF)
      questionnaire. The satisfaction of patients and partners were evaluated by a
      telephone interview using the erectile dysfunction inventory of treatment
      satisfaction (EDITS) questionnaire and EDITS partner survey. RESULTS: The overall
      major complication rate was higher in IPP group. PPI led to a significant
      improvement in IIEF scores in both groups. For IPP and SPP groups the average
      EDITS scores were 78+/-11and 57+/-8, respectively, and that for the partners were
      72+/-10 and 49+/-7, respectively (p<0.05). CONCLUSION: Although the IPP
      implantation have better satisfaction rates, the SPP implantation is still a
      viable treatment option in the surgical treatment of ED because of low cost and
      high durability with acceptable satisfaction rates.

PMID- 26200548
TI  - Quality of life evaluation of patients with neurogenic bladder submitted to
      reconstructive urological surgeries preserving the bladder.
AB  - Treatment of neurogenic bladder (BN) aims to upper urinary tract protection. When
      the conservative clinical measures are insufficient, surgical treatment is
      indicated. Though admittedly important, the quality of life (QoL) has been little
      studied in these patients, there are even contradictory results. The aim of this
      study was to evaluate QoL before and after bladder augmentation in patients with
      BN refractory to medical treatment. We analyzed, prospectively, the data of 67
      patients who underwent surgical treatment for BN by questionnaire SF-36((r)) and
      Qualiveen((r)) QoL before and after six months of operation. Comparisons using
      paired t-tests and Wilcoxon and the assumption of normality was assessed using
      the Shapiro-Wilk test were made. According to the analysis of the SF-36((r))
      questionnaire, the patients had higher QoL indices in the postoperative period in
      the areas functional capacity, general state of health, vitality, social aspects,
      emotional aspects and mental health (n = 67; p <0.05). The questionnaire also
      revealed Qualiveen((r)) best result in quality of life index in the postoperative
      period, and show lower specific negative impact by urinary problems (n = 36; p
      <0.05). The results show that, despite not being the main objective, the bladder
      augmentation results in significant improvement in QoL, probably related to the
      perception of better health and the resolution of urinary incontinence. Thus, the
      bladder augmentation associated with other urologic reconstruction techniques
      allows the upper urinary tract protection, and contribute to a better quality of
      life of patients with BN.

PMID- 26200550
TI  - Do Foley Catheters Adequately Drain the Bladder? Evidence from CT Imaging
      Studies.
AB  - INTRODUCTION: The Foley catheter has been widely assumed to be an effective means
      of draining the bladder. However, recent studies have brought into question its
      efficacy. The objective of our study is to further assess the adequacy of Foley
      catheter for complete drainage of the bladder. MATERIALS AND METHODS: Consecutive
      catheterized patients were identified from a retrospective review of contrast
      enhanced and non-contrast enhanced computed tomographic (CT) abdomen and pelvis
      studies completed from 7/1/2011-6/30/2012. Residual urine volume (RUV) was
      measured using 5mm axial CT sections as follows: The length (L) and width (W) of
      the bladder in the section with the greatest cross sectional area was combined
      with bladder height (H) as determined by multiplanar reformatted images in order
      to calculate RUV by applying the formula for the volume (V) of a sphere in a
      cube:V=(pi/6)*(L*W*H). RESULTS: RUVs of 167 (mean age 67) consecutively
      catheterized men (n=72) and women (n=95) identified by CT abdomen and pelvis
      studies were calculated. The mean RUV was 13.2 mL (range: 0.0 mL-859.1 mL,
      standard deviation: 75.9 mL, margin of error at 95% confidence:11.6 mL). Four
      (2.4%) catheterized patients had RUVs of >50 mL, two of whom had an improperly
      placed catheter tip noted on their CT-reports. CONCLUSIONS: Previous studies have
      shown that up to 43% of catheterized patients had a RUV greater than 50 mL,
      suggesting inadequacy of bladder drainage via the Foley catheter. Our study
      indicated that the vast majority of patients with Foley catheters (97.6%), had
      adequately drained bladders with volumes of <50 mL.

PMID- 26200549
TI  - Relationship between pseudoexfoliation syndrome and erectile dysfunction: a
      possible cause of endothelial dysfunction for development of erectile
      dysfunction.
AB  - OBJECTIVES: Pseudoexfoliation syndrome (PES) is a common age-related
      fibrillopathy related to accumulation of pseudoexfoliation material (PEM) in
      certain places in the body, especially blood vessels. Erectile dysfunction (ED)
      is another condition related to vascular pathology and in this study it is aimed
      to identify the relationship between ED and PES. MATERIALS AND METHODS: Data of
      92 patients were investigated. There were 34 patients in the PES group and 58
      patients in the control group. Presence of diabetes, hypertension, smoking
      history, BMI, and serum levels of lipids and testosterone were recorded. The
      groups were compared for ED rates and severity. Also logistic regression analysis
      was performed to identify independent risk factors for development of ED.
      RESULTS: Mean age of the population was 67.3. No significant difference was
      observed between the two groups regarding the presece of DM, HT, smoking, BMI and
      laboratory measurements. ED rate was significantly higher in the PES group (70.6%
      vs 48.3%, p=0.002). Also, severe ED rate was higher in the PES group (p=0.002).
      PES was detected as an independent risk factors for the development of ED.
      CONCLUSION: ED is a possible consequence of PES. ED rate and severity is found to
      be higher in the PES group and PES is detected as an independent risk factor for
      development of ED. Patients with PES should be informed about development of ED
      and further prospective trials with objective measurements of penile blood flow
      should be conducted to verify the erectile status and penile blood flow in PES
      patients.

PMID- 26200551
TI  - Ultrasound evaluation of obstructive uropathy and its hemodynamic responses in
      southwest Nigeria.
AB  - PURPOSE: To determine the renal arterial hemodynamic changes induced by
      obstructive uropathy using Doppler ultrasonography. MATERIALS AND METHODS: 60
      adult subjects with suspected obstructive uropathy and 60 asymptomatic apparently
      healthy controls with normal renal ultrasound features were evaluated. B-mode
      sonography of the kidneys and spectral Doppler examination of the renal
      interlobar arteries of all the participants were performed. The mean resistive
      indices (mRI) of both interlobar arteries were obtained and compared to that of
      the controls. The mRI of bilaterally obstructed kidneys were also compared with
      the mRI of unilaterally obstructed kidneys. RESULTS: The mRI of the right and
      left kidneys of subjects were 0.72+/-0.04 and 0.69+/-0.06 while those of the
      controls were 0.64+/-0.04 and 0.63+/-0.03 respectively. The mRI for the grades of
      caliectasis increased from grade I (0.72+/-0.03) to grade II (0.73+/-0.03) and
      grade III (0.73+/-0.02) but fell within the most severe levels of obstruction
      (0.69+/-0.07). There was no statistically significant relationship between the
      grades of caliectasis and unilateral or bilateral obstruction for both kidneys.
      The results show a sensitivity and specificity of 86.7% and 90% respectively when
      mRI>=0.7 was used to determine presence of obstruction. CONCLUSION: Renal duplex
      sonography is highly sensitive and specific for diagnosis of obstructive
      uropathy. Increased resistive index of the obstructed kidney may be a useful
      diagnostic tool in situations where intravenous urography cannot be done or is
      contraindicated.

PMID- 26200552
TI  - To tell or not: parental thoughts on disclosure of urologic surgery to their
      child.
AB  - PURPOSE: Literature pertaining to surgical disclosure to the pediatric patient is
      lacking. We hypothesized parents would find it difficult to disclose urologic
      surgery to a child. MATERIALS AND METHODS: Parents of patients <5 years old
      undergoing urologic surgery were contacted for telephone survey. Parents were
      asked about future plans of surgical disclosure, comfort with disclosure, and any
      support received. RESULTS: 98 parents consented to study participation. 87% of
      surgeries were on the genitalia with 62% being minor genitalia surgery (i.e.
      circumcision). 70% of parents would tell their child about minor genital surgery
      while 84% would tell about major genital surgery (p=0.07). 4 of 20 parents of
      children undergoing hypospadias repair (major genital surgery) did not plan to
      tell their child about surgery. All parents of children undergoing non-genital
      surgery would tell. Of all parents planning to tell their children about surgery,
      only 14% were nervous. 34% of parents would find guidance in talking to their
      child helpful despite the majority (90%) stating no guidance had ever been
      provided. CONCLUSIONS: Parents seem comfortable discussing urologic surgeries
      with a child but about 1/3 would appreciate further counseling. 20% of parents of
      children undergoing hypospadias repair hope to avoid telling their child.

PMID- 26200553
TI  - Metabolic and testicular effects of the long-term administration of different
      high-fat diets in adult rats.
AB  - PURPOSE: To evaluate the effects of different high-fat diets on body mass,
      carbohydrate metabolism and testicular morphology in rats seven months old.
      MATERIALS AND METHODS: Male Wistar rats were divided into four groups: SC
      (standard chow), HF-S (high fat diet rich in saturated fatty acids), HF-P (high
      fat diet rich in polyunsaturated fatty acids), HF-SP (high fat diet rich in
      saturated and polyunsaturated fatty acids). The rats were fed for 16 weeks. Blood
      samples, testes and genital fat deposits were collected for analysis. Data were
      analyzed by one-way ANOVA and Bonferroni post hoc test, considering p<0.05 as
      statistically significant. RESULTS: Different high-fat diets promoted an increase
      in the body mass (p<0.0001). The genital fat deposits were higher in the high-fat
      groups (HF-S, HF-P, HF-SP) (p=0.0004). Regarding serum parameters, the animals in
      the HF-S and HF-SP groups presented hyperglycemia (p=0.0060), hyperinsulinemia
      (p=0.0030) and hypercholesterolemia (p=0.0021). All of the hyperlipidemic groups
      showed hyperleptinemia (p=0.0019). Concerning the testis, the HF-S group showed a
      reduction on the seminiferous epithelium height (p=0.0003) and cell proliferation
      (p=0.0450). Seminiferous tubule diameter was lower in the HF-SP than in the SC
      group (p=0.0010). CONCLUSIONS: The high fat diet administration, independent of
      the lipid quality, promotes overweight. Diet rich in saturated fatty acids (lard)
      alters the carbohydrate metabolism and the testicular morphology with reductions
      of seminiferous epithelium height, seminiferous tubule diameter and cell
      proliferation which could be related to a disturbance of spermatogenesis.

PMID- 26200554
TI  - Beneficial effect of pentoxifylline into the testis of rats in an experimental
      model of unilateral hindlimb ischemia/reperfusion injury.
AB  - OBJECTIVE: The objective of the present study was to investigate the role of
      pentoxifylline (PTX) on remote testicular injury caused by unilateral hind limb
      ischemia/reperfusion of rats. MATERIALS AND METHODS: Twenty healthy male Wistar
      rats were allocated randomly into two groups: ischemia/reperfusion (IR group) and
      ischemia/reperfusion + pentoxifylline (IR+PTX group). Ischemia was induced by
      placement of a rubber tourniquet at the greater trochanter for 2h. Rats in IR+PTX
      group received PTX (40 mg/kg IP) before the reperfusion period. At 24h after
      reperfusion, testes were removed and levels of superoxide dismutase (SOD),
      malondialdehyde (MDA), catalase (CAT) and myeloperoxidase (MPO) activity were
      determined in testicular tissues. Three rats of each group were used for wet/ dry
      weight ratio measurement. Testicular tissues were also examined
      histopathologically under light microscopy. RESULTS: Activities of SOD and CAT in
      testicular tissues were decreased by ischemia/ reperfusion (P<0.05).
      Significantly increased MDA levels in testicular tissues were decreased by PTX
      treatment (P<0.05). MPO activity in testicular tissues in the IR group was
      significantly higher than in the IR+PTX group (P<0.05). The wet/dry weight ratio
      of testicular tissues in the IR group was significantly higher than in the IR+PTX
      group (P<0.05). Histopathologically, there was a statistically significant
      difference between two groups (P<0.05). CONCLUSIONS: According to histological
      and biochemical findings, we conclude that PTX has preventive effects in the
      testicular injury induced by hind limb ischemia/reperfusion.

PMID- 26200555
TI  - A Novel Approach for the Treatment of Radiation-Induced Hemorrhagic Cystitis with
      the GreenLightTM XPS Laser.
AB  - INTRODUCTION: The treatment of pelvic malignancies with radiotherapy can develop
      severe sequelae, especially radiation-induced hemorrhagic cystitis. It is a
      progressive disease that can lead to the need for blood transfusion,
      hospitalizations, and surgical interventions. This tends to affect the quality of
      life of these patients, and management can at times be difficult. We have
      evaluated the GreenLight Xcelerated Performance System (XPS) with TruCoag,
      although primarily used for management of benign prostatic hypertrophy (BPH), for
      the treatment of radiation-induced hemorrhagic cystitis. MATERIALS AND METHODS:
      After International Review Board (IRB) approval, a retrospectivechart review was
      performed in addition to a literature search. A series of four male patients,
      mean age of 81 years, with radiation-induced hemorrhagic cystitis secondary to
      radiotherapy for pelvic malignancies (3 prostate cancer, 1 rectal cancer) were
      successfully treated with the GreenLight laser after unsuccessful treatment with
      current therapies described in the literature. RESULTS: All four patients treated
      with the GreenLight laser had resolution of their hematuria after one treatment
      and were discharge from the hospital with clear urine. CONCLUSION: The GreenLight
      XPS laser shows promising results for the treatment of patients with radiation
      induced hemorrhagic cystitis, and deserves further evaluation and validation,
      especially since there is limited data available in the literature regarding the
      use of this technology for the treatment of this devastating condition.

PMID- 26200556
TI  - Testicular calculus: A rare case.
AB  - BACKGROUND: Testicular calculus is an extremely rare case with unknown etiology
      and pathogenesis. To our knowledge, here we report the third case of testicular
      calculus. A 31-year-old man was admitted to our clinic with painful solid mass in
      left testis. After diagnostic work-up for a possible testicular tumour, he
      underwent inguinal orchiectomy and histopathologic examination showed a
      testicular calculus. Case hypothesis: Solid testicular lesions in young adults
      generally correspond to testicular cancer. Differential diagnosis should be done
      carefully. Future implications: In young adults with painful and solid testicular
      mass with hyperechogenic appearance on scrotal ultrasonography, testicular
      calculus must be kept in mind in differential diagnosis. Further reports on this
      topic may let us do more clear recommendations about the etiology and treatment
      of this rare disease.

PMID- 26200557
TI  - Rapid intraoperative tissue expansion with Foley catheter in a challenging
      cripple Hypospadias.
AB  - Failed hypospadiass cases may result in hypovascular, scarred penis with residual
      penile chordee and leave the patient with minimal residual skin for penile
      resurfacing and urethroplasty. Local tissue expansion has become a good
      alternative to provide skin for penis by using expanders however they require
      long periods of time for expansion. Besides, rapid tissue expansion was also
      described in different tissues.We used rapid intraoperative expansion technique
      by using a Foley catheter in a failed hypospadias case who had minimal residual
      skin secondary to infection and we concluded that rapid intraoperative tissue
      expansion with Foley catheter is an effective, feasible reconstructive method for
      easy dissection and penile resurfacing in failed hypospadiass cases. 

PMID- 26200558
TI  - Retroperitoneal Hygroma.
AB  - We present a 46-year-old white male with a retroperitoneal hygroma protruding
      from the right flank. 

PMID- 26200559
TI  - Vesicoenteric fistula caused by bladder diverticulitis: MRI Findings.

PMID- 26200560
TI  - Distal spermatic cord peritoneal stripping: an adjunct technique during inguinal
      orchiopexy.

PMID- 26200561
TI  - Forgotten and fragmented ureteral j stent with stone formation: combined
      endoscopic management.
AB  - OBJECTIVE: Ureteral stents are widely used in endo-urological procedures.
      However, ureteral stents can be forgotten and cause serious complications,
      including fragmentation, migration and urosepsis.There are few reports about
      forgotten and fragmented ureteral stents with stone formation. We aimed to
      present this rare case with successful combined endo-urological management.

PMID- 26200562
TI  - RE: Validation of the brazilian version of the expanded prostate cancer index
      composite (EPIC) for patients submitted to radical prostatectomy.

PMID- 26200563
TI  - A new technique of bladder neck reconstruction during radical prostatectomy in
      patients with prostate cancer.
AB  - PURPOSE: To evaluate continence after radical prostatectomy in prostate cancer
      patients, in whom a new method of the bladder neck reconstruction (BNR) using
      deep dorsal stitch was implemented (deep single stitch through all bladder layers
      directly dorsal to the bladder opening after " tennis racket" reconstruction) and
      to provide justification for its use by means of anatomical study in cadavers.
      MATERIAL AND METHODS: Open radical retropubic prostatectomy was performed in 84
      patients: 39 patients with a new BNR method used to improve continence and
      control group of 45 patients with standard "tennis racket" BNR. Median follow-up
      was 14 months in control group and 12 months in study group. Continence recovery
      was accessed early postoperatively and every 3 months thereafter. Anatomical
      study was performed on 2 male fresh cadavers reproducing two different BNR
      techniques to clarify any underlying continence related mechanisms. RESULTS:
      Patients with new BNR achieved full continence significantly faster (p=0.041),
      but the continence rates after 12 months were similar between groups. The
      severity of incontinence up to month 9 was significantly reduced in BNR group.
      The anastomotic stricture rate was not affected. Applying new BNR to the cadaver
      model revealed effects on early continence, namely presence of proximal passive
      closure mechanism in area of bladder neck. CONCLUSIONS: Continence in patients
      with the new BNR method using deep dorsal stitch recovered significantly faster.
      Moreover, a reduced grade of residual incontinence was documented. The effect was
      non-significant at month 12 of follow-up, meaning that only early effect was
      present.

PMID- 26200564
TI  - Surgical treatment is effective in severe cases of exercise-induced laryngeal
      obstruction: A follow-up study.
AB  - CONCLUSIONS: Surgery is an effective treatment in severe cases of supraglottic
      exercise-induced laryngeal obstruction (E-ILO). Conservatively treated subjects
      and subjects tested negative for E-ILO, who still experience breathing problems 1
      3 years after diagnosis, tend to adjust their physical activity to a greater
      extent than surgically treated subjects. OBJECTIVE: To investigate how symptoms
      and level of physical activity change over time in patients with E-ILO who have
      undergone surgery, patients with E-ILO treated conservatively and patients who
      tested negative for laryngeal obstruction at continuous laryngoscopy exercise
      test (CLE-test). METHODS: Patients referred for exercise-induced breathing
      difficulties answered questionnaires at diagnostic CLE-test and at follow-up.
      Questions regarded exercise-induced breathing problems, current physical activity
      level, and medical history of asthma and perennial allergy. RESULTS: Out of 84
      invited subjects, 59 (70%) answered both questionnaires. Surgically treated
      subjects had less breathing problems at follow-up compared with conservatively
      treated subjects and subjects who tested negative (p < 0.001). None of the
      surgically treated subjects were less physically active or had changed sport due
      to exercise-induced dyspnoea, whereas 41.7% of the conservatively treated
      subjects had made such adjustments (p < 0.001).

PMID- 26200565
TI  - Localized Thyroid Tissue Ablation by High Intensity Focused Ultrasound: Volume
      Reduction, Effects on Thyroid Function and Immune Response.
AB  - PURPOSE: The aim of this study was to assess the effectiveness of high intensity
      focused ultrasound (HIFU) in reducing thyroid nodule volume while preserving
      thyroid function as measured by immunological response. MATERIALS AND METHODS: 12
      patients (9 females) whose average age was 56.9 years (37 - 81) were treated with
      HIFU in an ambulatory setting. All patients had a single benign thyroid nodule
      treated in one HIFU session. The median nodular outline volume (NOV) was 3.4  ml
      (range 0.6 - 5.0  ml). The therapeutic ultrasound probe (Echopulse((r)) THC900
      888-H) used works with a frequency of 3  MHz, reaching temperatures of 80 - 90
      degrees  C and a mean output between 87.6 and 192.8  W. To assess possible
      effects of HIFU on thyroid function, serum levels of triiodothyronine (T3),
      thyroxine (T4), thyrotropin (TSH), thyroglobulin (hTg) and antibodies against
      thyroglobulin (TAbs), thyrotropin receptors (TRAbs) and thyroid peroxidase
      (TPOAbs) were measured at enrollment, 24-hours post-HIFU treatment and at 3-month
      follow-up.Pre- post thyroglobulin reduction was measured to evaluate the success
      of ablation and the nodular outline volume (NOV) was evaluated at baseline and
      the 3-month follow-up to assess effectiveness. RESULTS: All measured hormone
      levels were within normal ranges and remained stable (p > 0.05). No clinically
      meaningful immune reaction was induced (p > 0.05). Thyroglobulin serum levels
      increased significantly at 24 hours after ablation (p < 0.05) and decreased
      significantly at the 3-month follow-up (p < 0.05), returning to pre-ablative
      levels. The median reduction in nodular outline volume (NOV) was 55 % (p < 0.05).
      CONCLUSION: HIFU is a safe and effective alternative for treating benign thyroid
      nodules, while preserving thyroid function. Further investigations with multiple
      treatments should be conducted to evaluate whether additional treatments can
      achieve greater volume reduction.

PMID- 26200566
TI  - Evaluation of Bone Marrow Infiltration in Non-Neuropathic Gaucher Disease
      Patients with Use of Whole-Body MRI--A Retrospective Data Analysis.
AB  - PURPOSE: To evaluate whole-body magnetic resonance imaging (WB-MRI) for the
      assessment of bone marrow infiltration in patients with confirmed Gaucher disease
      type 1 under long-term enzyme replacement therapy (ERT). MATERIALS AND METHODS:
      This retrospective data analysis included 38 patients in two subgroups. Group A:
      10 females, 9 males, 15-29 years, mean age 22 years and Group B: 11 females, 8
      males, 29-77 years, mean age 49 years, all treated with alglucerase or
      imiglucerase for at least 12.5 years. Whole-body MRI was carried out in all
      patients using a standard MRI protocol. Two radiologists assessed all MR images
      retrospectively with the use of three different MRI score systems: The bone
      marrow burden (BMB) score, the Dusseldorf-Gaucher score (DGS) and the vertebra
      disc ratio (VDR). As a clinical component, severity score index type 1 (GD-DS3)
      was determined. RESULTS: In both groups the MR scores showed low to moderate
      pathologic levels but no statistically significant difference was found between
      both groups. The median scores in group A/group B were 7.00/9.00 for the BMB
      score (p=0.07), 4.00/3.00 for the DGS score (p=0.062) and 1.54/1.62 for the VDR
      score (p=0.267). The GD-DS3 score was statistically significantly different
      between both groups (1.6/3.9, p=0.000) and osseous Gaucher disease complications
      were only found in group B. CONCLUSION: Bone marrow involvement and typical
      clinical manifestations are reduced to a minimum, when ERT starts immediately
      after the confirmed diagnosis of Gaucher disease type 1. The applied MR scores
      are useful markers to control bone marrow infiltration under enzyme replacement
      therapy in older patients. Pathologic MR scores in young patients may reflect
      postponed fat conversion of the juvenile bone marrow. This issue has to be
      examined in further studies. KEY POINTS: Whole-body MRI is valuable for the
      staging of Gaucher disease type 1. Osseous complications are reduced to a minimum
      in early treated patients. MR score systems have to be adjusted in young Gaucher
      patients.

PMID- 26200567
TI  - [Combined percutaneous thrombectomy in acute transplant venous thrombosis after
      en bloc pancreas transplantation into the right-sided pelvis].

PMID- 26200568
TI  - [Dorsal thoracic arachnoid septa - detection in MRI with time resolved sequences
      (CineTrueFISP sequence)].

PMID- 26200569
TI  - Venous Obstruction in Asymptomatic Patients Undergoing First Implantation or
      Revision of a Cardiac Pacemaker or Implantable Cardioverter-Defibrillator: A
      Retrospective Single Center Analysis.
AB  - PURPOSE: To investigate the incidence and possible risk factors of upper deep
      vein obstruction in patients both prior to first cardiac device implantation and
      before device revision. MATERIALS AND METHODS: Records of asymptomatic patients
      undergoing contrast venography prior to implantation or revision of a cardiac
      device from 09/2009 to 04/2012 were reviewed. Venograms were used to determine
      the presence of venous obstruction. Interrelations between the incidence of
      venous obstruction and patient- or device-related parameters were identified
      using Fisher's exact test and univariate logistic regression. Multivariate
      logistic regression was used to identify independent predictors of venous
      obstruction. RESULTS: 456 patients met the inclusion criteria (330 males, 126
      females, 67.8  +/-  12.9 years). 100 patients underwent first implantation, and
      356 patients underwent device revision (mean time since implantation 82.5  +/- 
      75.3 months). Venous obstruction was present in 11.0 % and 30.1 % before
      implantation and revision, respectively. Only presence of ventricular escape
      rhythm was significantly related to venous occlusion (p < 0.001) prior to first
      implantation. Prior to revision, significant predictors were male sex (p = 0.01),
      time since implantation (p < 0.0001), presence of escape rhythm (p = 0.02),
      compromised coagulation (p = 0.02), phenprocoumon (p = 0.005), and peripheral
      arterial disease (p = 0.01). CONCLUSION: Although several risk factors could be
      identified, reliable prediction of venous obstruction was not possible.
      Therefore, we advocate performing venography in all patients prior to device
      revision or upgrade to avoid complications. In cases of first device
      implantation, the risks associated with venography should be weighed against the
      surprisingly high rate of deep upper vein obstruction.

PMID- 26200571
TI  - Enhancing the Voice of Faculty in the Association of American Medical Colleges:
      The Evolution of Faculty in U.S. Medical Schools and the Transformation of the
      Council of Academic Societies Into the Council of Faculty and Academic Societies.
AB  - Since its inception in 1966, the Council of Academic Societies (CAS) represented
      academic faculty in the governance structure of the Association of American
      Medical Colleges (AAMC). As the role of faculty in the academic health center of
      the 21st century has evolved (e.g., the number of faculty members has increased,
      contact hours with trainees per individual faculty member have decreased, the
      faculty has aged), new models for representation have become necessary. Because
      of the structure and requirements for organizational membership, CAS was not
      representing faculty as broadly as possible, so a redesign was necessary. In
      November 2012, the AAMC Assembly adopted changes to its bylaws creating the new
      Council of Faculty and Academic Societies. The new design increases the
      opportunity for all schools to be represented by both junior and senior faculty
      members while retaining society membership and, therefore, representation of the
      breadth of specialties in academic medicine. The new council's structure better
      facilitates meeting its charge: to identify critical issues facing academic
      medicine faculty members; to provide faculty with a voice as the AAMC addresses
      those issues through the creation and implementation of AAMC programs, services,
      and policies; and to serve as a communications conduit between the AAMC and
      faculty regarding matters related to the core missions of academic medicine. 

PMID- 26200570
TI  - Lopinavir and atazanavir in pregnancy: comparable infant outcomes, virological
      efficacies and preterm delivery rates.
AB  - OBJECTIVES: The aim of the study was to identify differences in infant outcomes,
      virological efficacy, and preterm delivery (PTD) outcome between women exposed to
      lopinavir/ritonavir (LPV/r) and those exposed to atazanavir/ritonavir (ATV/r).
      METHODS: A retrospective case note review was carried out. The case notes of 493
      women who conceived while on LPV/r or ATV/r or initiated LPV/r or ATV/r during
      pregnancy and who delivered between 1 September 2007 and 30 August 2012 were
      reviewed. Data collected included demographics, antiretroviral use, HIV markers,
      and pregnancy and infant outcomes. Infant outcomes, virological efficacies and
      PTD rates for LPV/r and ATV/r were compared. RESULTS: A total of 306 women
      received LPV/r (82 conceiving while on the drug and 224 commencing it post
      conception) and 187 received ATV/r (96 conceiving while on the drug and 91
      commencing it post-conception). Comparing the two protease inhibitors (PIs),
      viral suppression rates were similar and, in women starting antiretroviral
      therapy (ART) post-conception, the median times to first undetectable HIV viral
      load were not significantly different (P = 0.64). PTD rates did not differ by
      therapy overall (ATV/r, 13%; LPV/r, 14%) or when considering the timing of first
      exposure (conceiving on ART, P = 0.81; commencing ART in pregnancy, P = 0.08).
      Poor fetal outcomes were very uncommon. There were two transmissions, giving a
      mother-to-child transmission (MTCT) rate of 0.4% (95% confidence interval 0.05
      1.5%). CONCLUSIONS: Both ART regimens were well tolerated and successful in
      preventing MTCT. No significant differences in tolerability or in pregnancy or
      infant outcomes were observed, which supports the provision of a choice of PI in
      pregnancy.

PMID- 26200572
TI  - Provider Board Certification Status and Practice Patterns in Total Knee
      Arthroplasty.
AB  - PURPOSE: The presumption that board certification directly affects the quality of
      clinical care is a topic of ongoing discussion in medical literature. Recent
      studies have demonstrated disparities in patient outcomes associated with type of
      anesthesia provided for total knee arthroplasty (TKA); improved outcomes are
      associated with neuraxial (or regional) versus general anesthesia. Whether board
      certified (BC) and non-board-certified (nBC) anesthesiologists make different
      choices in the anesthetic they administer is unknown. The authors sought to study
      potential associations of board certification status with anesthesia practice
      patterns for TKA. METHOD: The authors accessed records of anesthetics provided
      from 2010 to 2013 from the National Anesthesia Clinical Outcomes Registry
      database. They identified TKA cases using Clinical Classifications Software and
      Current Procedural Terminology codes. The authors divided practitioners into two
      groups: those who were BC and those who were nBC. For each of these groups, the
      authors compared the following: their patient populations, the hospitals in which
      they worked, the nature of their practices, and the anesthetics they administered
      to their patients. RESULTS: BC anesthesiologists provided care for 81.7% of
      97,508 patients having TKA; 18.3% were treated by nBC anesthesiologists. BC
      anesthesiologists administered neuraxial/regional anesthesia more frequently than
      nBC anesthesiologists (41.4% versus 21.2%; P < .001). CONCLUSIONS: The rates at
      which regional/neuraxial anesthesia were administered for TKA were relatively
      low, and there were significant differences in practice patterns of BC and nBC
      anesthesiologists providing care for patients undergoing TKA. More research is
      necessary to understand the causes of these disparities.

PMID- 26200573
TI  - Building a Generation of Physician Advocates: The Case for Including Mandatory
      Training in Advocacy in Canadian Medical School Curricula.
AB  - There is an increasing focus on the social accountability of physicians as
      individuals, and of medicine itself. This has led to increasing emphasis on
      physician advocacy from a wide variety of institutions. The physician advocacy
      concept is now part of the Health Advocacy competency mandated by the Royal
      College of Physicians and Surgeons of Canada. Despite its growing prominence,
      physician advocacy remains poorly integrated into current medical undergraduate
      curricula. The authors recommend how and why curricular reform should proceed;
      they focus on Canadian medical education, although they hope their views will be
      useful in other countries as well.The authors discuss conflicting definitions of
      physician advocacy, which have previously hampered curriculum development
      efforts, and suggest a way of reconciling the conflicts. They review current gaps
      in advocacy-related curricula, suggest that these can be addressed by
      incorporating practice-based and skills acquisition elements into current
      didactic teaching, and offer several strategies by which an advocacy curriculum
      could be implemented, ranging from small modifications to current curriculum to
      developing new competencies in medical education nationally.The authors present a
      case for making an advocacy curriculum mandatory for every Canadian medical
      trainee; they argue that teaching trainees how to fulfill their professional
      responsibility to advocate may also help them meet the social accountability
      mandate of medical school education. Finally, the authors explain why making the
      development and implementation of a mandatory, skill-based curriculum in advocacy
      should be a priority. 

PMID- 26200574
TI  - Laboratory Medicine Education at U.S. Medical Schools: A 2014 Status Report.
AB  - PURPOSE: To assess the current state of laboratory medicine education at U.S.
      medical schools. METHOD: From 2013 to 2014, the authors surveyed the appropriate
      dean, department chair, or undergraduate education director at each U.S. medical
      school accredited by the Liaison Committee on Medical Education about the state
      of laboratory medicine education, curriculum and competency assessment, and
      barriers to education at his or her institution. The authors used descriptive
      statistics to analyze the results. RESULTS: The authors received 98 (75%)
      responses. Eighty-two schools (84%) offered course work in laboratory medicine;
      76 (78%) required it. The median number of hours of required course work was
      12.5, with 8.0 devoted to lectures and 4.5 to small-group, problem-based learning
      and/or laboratory sessions. Only 8 schools required training in a clinical
      setting. Fewer than half reported regular, formal review of the laboratory
      medicine curriculum. The assessment of students' competency in laboratory
      medicine was rare (8 schools), and only half of respondents were aware of
      published curriculum guidelines. Barriers to teaching laboratory medicine
      included lack of sufficient time in the preclinical curriculum (86; 88%) or
      clinical curriculum (84; 86%), lack of knowledge of best laboratory practices by
      residents (70; 72%), lack of student interest (62; 63%), and lack of knowledge by
      attending physicians (58; 59%). Half of respondents were likely to use a national
      standardized examination to assess competency in laboratory medicine, if one was
      available. CONCLUSIONS: Significant opportunities exist to improve laboratory
      medicine education, including in the proper use and interpretation of clinical
      laboratory testing.

PMID- 26200575
TI  - The WWAMI Targeted Rural Underserved Track (TRUST) Program: An Innovative
      Response to Rural Physician Workforce Shortages.
AB  - PROBLEM: Too few physicians practice in rural areas. To address the physician
      workforce needs of the Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI)
      region, the University of Washington School of Medicine developed the Targeted
      Rural Underserved Track (TRUST) program in August 2008. TRUST is a four-year
      curriculum centered on a clinical longitudinal continuity experience with
      students repeatedly returning to a single site located in a rural community or
      small city. APPROACH: The overarching theme of TRUST is one of linkages. Students
      are strategically linked to a rural community, known as their TRUST continuity
      community (TCC). The program begins with a targeted admission process and
      combines new and established programs and curricular elements to form a cohesive
      educational experience. This experience includes repeated preclinical visits,
      clerkships, and electives at a student's TCC, and rural health courses, the
      Underserved Pathway, and the Rural Underserved Opportunities Program (which
      includes a community-oriented primary care scholarly project). OUTCOMES: TRUST
      was piloted in Montana in 2008. With the matriculating class of 2015, every state
      in the WWAMI region will have TRUST students. From 2009 (the year targeted
      admissions began) to 2015, 123 students have been accepted into TRUST. Thirty
      three students have graduated. Thirty (90.9%) of these graduates have entered
      residencies in needed regional specialties. NEXT STEPS: Next steps include
      implementing a robust evaluation program, obtaining secure institutional
      programmatic funding, and further developing linkages with regional rural
      residency programs. TRUST may be a step forward in addressing regional needs and
      a reproducible model for other medical schools.

PMID- 26200576
TI  - The Importance of Situational Awareness: A Qualitative Study of Family Members'
      and Nurses' Perspectives on Teaching During Family-Centered Rounds.
AB  - PURPOSE: Family-centered rounds (FCR) has become a leading model for pediatric
      inpatient rounding. During FCR, faculty must balance trainees' educational needs
      with patient care priorities. Investigators have examined trainees' views on
      effective teaching during FCR, but none have evaluated what family members and
      nurses consider to be effective teaching behaviors of attending physicians. The
      authors sought to explore family members' and nurses' perspectives on effective
      teaching behaviors during FCR. METHOD: The authors conducted (2012-2013) a
      qualitative study of families and nurses at an academic children's hospital where
      FCR is the standard model for inpatient rounds. Nurses and families familiar with
      FCR participated in separate focus groups. The authors reviewed focus group
      transcripts using techniques of qualitative content analysis; they generated
      codes and developed categories, supported by illustrative quotations. RESULTS:
      Fifteen nurses and 13 family members participated in the focus groups. The
      unifying theme was that situational awareness on behalf of the attending
      physician is essential for FCR to be educational for all participants. The
      authors identified four categories of awareness-(1) cognitive factors, (2)
      logistics and time management, (3) physical environment, (4) emotional state-and
      developed a set of effective teaching strategies based on participants' comments.
      CONCLUSIONS: The findings of this study support previous work identifying
      effective FCR teaching strategies, but this study is the first to include the
      perspectives of families and nurses. The inclusion of these participants provides
      a framework for faculty development and training to improve the educational value
      of FCR.

PMID- 26200577
TI  - Close Reading and Creative Writing in Clinical Education: Teaching Attention,
      Representation, and Affiliation.
AB  - Medical educators increasingly have embraced literary and narrative means of
      pedagogy, such as the use of learning portfolios, reading works of literature,
      reflective writing, and creative writing, to teach interpersonal and reflective
      aspects of medicine. Outcomes studies of such pedagogies support the hypotheses
      that narrative training can deepen the clinician's attention to a patient and can
      help to establish the clinician's affiliation with patients, colleagues,
      teachers, and the self. In this article, the authors propose that creative
      writing in particular is useful in the making of the physician. Of the conceptual
      frameworks that explain why narrative training is helpful for clinicians, the
      authors focus on aesthetic theories to articulate the mechanisms through which
      creative and reflective writing may have dividends in medical training. These
      theories propose that accurate perception requires representation and that
      representation requires reception, providing a rationale for teaching clinicians
      and trainees how to represent what they perceive in their clinical work and how
      to read one another's writings. The authors then describe the narrative pedagogy
      used at the College of Physicians and Surgeons of Columbia University. Because
      faculty must read what their students write, they receive robust training in
      close reading. From this training emerged the Reading Guide for Reflective
      Writing, which has been useful to clinicians as they develop their skills as
      close readers. This institution-wide effort to teach close reading and creative
      writing aims to equip students and faculty with the prerequisites to provide
      attentive, empathic clinical care. 

PMID- 26200578
TI  - A Multisite Initiative to Increase the Use of Alcohol Screening and Brief
      Intervention Through Resident Training and Clinic Systems Changes.
AB  - PURPOSE: Screening and brief intervention (SBI) is a seldom-used evidence-based
      practice for reducing unhealthy alcohol use among primary care patients. This
      project assessed the effectiveness of a regional consortium's training efforts in
      increasing alcohol SBI. METHOD: Investigators combined alcohol SBI residency
      training efforts with clinic SBI implementation processes and used chart reviews
      to assess impact on SBI rates in four residency clinics. Data were derived from a
      random sample of patient charts collected before (2010; n = 662) and after (2011;
      n = 656) resident training/clinic implementation. Patient charts were examined
      for evidence that patients were asked about alcohol use by a validated screening
      instrument, the screening result (positive or negative), evidence that patients
      received a brief intervention, prescriptions for medications to assist
      abstinence, and referrals to alcohol treatment. Chi-square analyses identified
      differences in pre- and posttraining implementation of SBI practices. RESULTS:
      Following program implementation, screening with validated instruments increased
      from 151/662 (22.8%) at baseline to 543/656 (82.8%, P < .01), and identification
      of unhealthy alcohol use increased from 12/662 (1.8%) to 41/656 (6.3%, P < .01).
      Performance of brief interventions more than doubled (10/662 [1.5%] versus 24/656
      [3.7%], P < .01). There were no increases in the use of medications or referrals
      to treatment. CONCLUSIONS: Resident training combined with clinic implementation
      efforts can increase the delivery of evidence-based practices such as alcohol SBI
      in residency clinics.

PMID- 26200579
TI  - Embracing the Complexity of Valid Assessments of Clinicians' Performance: A Call
      for In-Depth Examination of Methodological and Statistical Contexts That Affect
      the Measurement of Change.
AB  - Assessments of clinicians' professional performance have become more entrenched
      in clinical practice globally. Systems and tools have been developed and
      implemented, and factors that impact performance in response to assessments have
      been studied. The validity and reliability of data yielded by assessment tools
      have been studied extensively. However, there are important methodological and
      statistical issues that can impact the assessment of performance and change that
      are often omitted or ignored by research and practice. In this article, the
      authors aim to address five of these issues and show how they can impact the
      validity of performance and change assessments, using empirical illustrations
      based on longitudinal data of clinicians' teaching performance. Specifically, the
      authors address the following: characteristics of a measurement scale that affect
      the performance data yielded by an assessment tool; different summary statistics
      of the same data that lead to opposing conclusions about performance and
      performance change; performance at the item level that does not easily translate
      to overall performance; how estimating performance change from two time-indexed
      measurements and assessing change retrospectively yield different results; and
      the context that affects performance and performance assessments. The authors
      explain how these issues affect the validity of performance assessments and offer
      suggestions for how to correct these issues. 

PMID- 26200580
TI  - Challenges to Learning Evidence-Based Medicine and Educational Approaches to Meet
      These Challenges: A Qualitative Study of Selected EBM Curricula in U.S. and
      Canadian Medical Schools.
AB  - PURPOSE: Evidence-based medicine (EBM) is a fixture in many medical school
      curricula. Yet, little is known about the challenges medical students face in
      learning EBM or the educational approaches that medical schools use to overcome
      these challenges. METHOD: A qualitative multi-institutional case study was
      conducted between December 2013 and July 2014. On the basis of the Association of
      American Medical Colleges 2012 Medical School Graduation Questionnaire data, the
      authors selected 22 U.S. and Canadian Liaison Committee on Medical Education
      accredited medical schools with graduates reporting confidence in their EBM
      skills. Participants were interviewed and asked to submit EBM curricular
      materials. Interviews were audio-recorded, transcribed, and analyzed using an
      inductive approach. RESULTS: Thirty-one EBM instructors (17 clinicians, 11
      librarians, 2 educationalists, and 1 epidemiologist) were interviewed from 17
      medical schools (13 in the United States, 4 in Canada). Four common EBM learning
      challenges were identified: suboptimal role models, students' lack of willingness
      to admit uncertainty, a lack of clinical context, and students' difficulty
      mastering EBM skills. Five educational approaches to these challenges that were
      common across the participating institutions were identified: integrating EBM
      with other courses and content, incorporating clinical content into EBM training,
      EBM faculty development, EBM whole-task exercises, and longitudinal integration
      of EBM. CONCLUSIONS: The identification of these four learner-centered EBM
      challenges expands on the literature on challenges in teaching and practicing
      EBM, and the identification of these five educational approaches provides medical
      educators with potential strategies to inform the design of EBM curricula.

PMID- 26200581
TI  - Addressing the Shortage of Geriatricians: What Medical Educators Can Learn From
      the Nurse Practitioner Training Model.
AB  - Physicians' career interest in geriatric medicine continues to wane at a time
      when the health care needs of older adults are increasing. Nurse practitioners
      have helped fill the U.S. physician gap by delivering outpatient care to older
      adults and can practice with full autonomy in many states. Nursing graduate
      school programs are preparing adult-gerontology primary care nurse practitioners
      to successfully deliver outpatient care services using a model of training with
      fewer requirements that is more flexible and of shorter duration compared with
      the training model for geriatricians. Nurse practitioners can also obtain initial
      certification and recertification with less time commitment and at lower cost
      than geriatricians. Whether the outpatient care provided by nurse practitioners
      is comparable to the care provided by physicians remains a subject of debate.
      However, as nurse practitioners' scope of practice expands, the perception exists
      that the outpatient clinical roles of adult-gerontology primary care nurse
      practitioners and geriatricians are similar. This raises questions about whether
      there are too many educational and certification requirements for geriatricians.
      The authors encourage medical educators to learn from the success of the nurse
      practitioner education model for training large numbers of primary care
      providers. They propose decreasing the duration of medical school and graduate
      medical education training for geriatricians and providing educational debt
      repayment programs as potential incentives to stimulate career interest in
      geriatric medicine.

PMID- 26200582
TI  - Recommendations for Writing Successful Grant Proposals: An Information Synthesis.
AB  - PURPOSE: To provide a detailed account of the nature and scope of recommendations
      for promoting faculty grant proposal success in academic medical settings.
      METHOD: The authors searched relevant scientific databases for articles related
      to techniques that promote faculty research proposal success, published from 2000
      through June 1, 2012. They applied standard information synthesis procedures for
      sifting abstracts, scrutinizing full texts, and abstracting data. RESULTS: The
      search identified 1,130 abstracts, which the authors narrowed to 83 for in-depth
      review. Of these, 53 unique articles fit the inclusion criteria. From these
      articles, the authors extracted 10 recommendations for writing successful grant
      proposals: (1) research and identify appropriate funding opportunities; (2) use
      key proposal components to persuade reviewers of project significance and
      feasibility; (3) describe proposed activities and their significance
      persuasively, clearly, and concisely; (4) seek review and feedback from
      colleagues; (5) establish a study design that is simple, logical, feasible, and
      appropriate for the research questions; (6) develop a timeline for the proposal
      process; (7) select a novel, high-impact project; (8) conduct an exhaustive
      literature review; (9) ensure that budgets are reasonable; and (10) consider
      interdisciplinary collaborations. CONCLUSIONS: These findings highlight that
      further institution-level development and interventions to support faculty grant
      writing success are warranted. Future research should employ more rigorous
      evaluation methods to move the field toward a stronger evidence base for
      determining which specific faculty development activities help increase funding.

PMID- 26200583
TI  - Teaching Quality Improvement in Graduate Medical Education: An Experiential and
      Team-Based Approach to the Acquisition of Quality Improvement Competencies.
AB  - PROBLEM: An emerging priority in medical education is the need to facilitate
      learners' acquisition of quality improvement (QI) competencies. Accreditation
      bodies in both Canada and the United States have included QI and patient safety
      in their core competencies. APPROACH: In 2010, the Department of Family Medicine
      at Queen's University designed a graduate medical education curriculum to engage
      residents in a clinical QI program that would meet accreditation requirements.
      Monthly didactic sessions were combined with an experiential, team-based QI
      project that aligned with existing clinic priorities. The curriculum spans the
      first year of residency and is divided into three stages: (1) Engaging, (2)
      Understanding, and (3) Improving and translating. In Stage 1, teams of residents
      select a clinical QI topic, engage stakeholders, and collect baseline data
      related to their topic. In Stage 2, they focus on understanding their problem,
      interpreting their results, and applying QI tools. In Stage 3, they develop
      change ideas, translate their knowledge, and prepare to hand over their project.
      OUTCOMES: This QI curriculum aided residents in effectively acquiring QI
      competencies and allowed them to experience real-world challenges, such as
      securing project buy-in, negotiating with peers, and developing solutions to
      problems. Unlike in many QI programs, residents learned how to improve quality
      rather than about QI; thus, they formed the necessary foundation to carry out QI
      work in the future. NEXT STEPS: The curriculum will be evaluated using a
      knowledge assessment and satisfaction tool and postproject resident interviews.
      Facilitators will focus more on improving faculty develop ment in QI.

PMID- 26200584
TI  - Facilitated Reflective Performance Feedback: Developing an Evidence- and Theory
      Based Model That Builds Relationship, Explores Reactions and Content, and Coaches
      for Performance Change (R2C2).
AB  - PURPOSE: To develop and conduct feasibility testing of an evidence-based and
      theory-informed model for facilitating performance feedback for physicians so as
      to enhance their acceptance and use of the feedback. METHOD: To develop the
      feedback model (2011-2013), the authors drew on earlier research which highlights
      not only the factors that influence giving, receiving, accepting, and using
      feedback but also the theoretical perspectives which enable the understanding of
      these influences. The authors undertook an iterative, multistage, qualitative
      study guided by two recognized research frameworks: the UK Medical Research
      Council guidelines for studying complex interventions and realist evaluation.
      Using these frameworks, they conducted the research in four stages: (1) modeling,
      (2) facilitator preparation, (3) model feasibility testing, and (4) model
      refinement. They analyzed data, using content and thematic analysis, and used the
      findings from each stage to inform the subsequent stage. RESULTS: Findings
      support the facilitated feedback model, its four phases-build relationship,
      explore reactions, explore content, coach for performance change (R2C2)-and the
      theoretical perspectives informing them. The findings contribute to understanding
      elements that enhance recipients' engagement with, acceptance of, and productive
      use of feedback. Facilitators reported that the model made sense and the phases
      generally flowed logically. Recipients reported that the feedback process was
      helpful and that they appreciated the reflection stimulated by the model and the
      coaching. CONCLUSIONS: The theory- and evidence-based reflective R2C2 Facilitated
      Feedback Model appears stable and helpful for physicians in facilitating their
      reflection on and use of formal performance assessment feedback.

PMID- 26200585
TI  - A Systematic Review of Tools Used to Assess Team Leadership in Health Care Action
      Teams.
AB  - PURPOSE: To summarize the characteristics of tools used to assess leadership in
      health care action (HCA) teams. HCA teams are interdisciplinary teams performing
      complex, critical tasks under high-pressure conditions. METHOD: The authors
      conducted a systematic review of the PubMed/MEDLINE, CINAHL, ERIC, EMBASE,
      PsycINFO, and Web of Science databases, key journals, and review articles
      published through March 2012 for English-language articles that applied
      leadership assessment tools to HCA teams in all specialties. Pairs of reviewers
      assessed identified articles for inclusion and exclusion criteria and abstracted
      data on study characteristics, tool characteristics, and validity evidence.
      RESULTS: Of the 9,913 abstracts screened, 83 studies were included. They
      described 61 team leadership assessment tools. Forty-nine tools (80%) provided
      behaviors, skills, or characteristics to define leadership. Forty-four tools
      (72%) assessed leadership as one component of a larger assessment, 13 tools (21%)
      identified leadership as the primary focus of the assessment, and 4 (7%) assessed
      leadership style. Fifty-three studies (64%) assessed leadership at the team
      level; 29 (35%) did so at the individual level. Assessments of simulated (n = 55)
      and live (n = 30) patient care events were performed. Validity evidence included
      content validity (n = 75), internal structure (n = 61), relationship to other
      variables (n = 44), and response process (n = 15). CONCLUSIONS: Leadership
      assessment tools applied to HCA teams are heterogeneous in content and
      application. Comparisons between tools are limited by study variability. A
      systematic approach to team leadership tool development, evaluation, and
      implementation will strengthen understanding of this important competency.

PMID- 26200587
TI  - Noncovalent Surface Locking of Mesoporous Silica Nanoparticles for Exceptionally
      High Hydrophobic Drug Loading and Enhanced Colloidal Stability.
AB  - Advances in water-insoluble drug delivery systems are limited by selective
      delivery, loading capacity, and colloidal and encapsulation stability. We have
      developed a simple and robust hydrophobic-drug delivery platform with different
      types of hydrophobic chemotherapeutic agents using a noncovalent gatekeeper's
      technique with mesoporous silica nanoparticles (MSNs). The unmodified pores offer
      a large volume of drug loading capacity, and the loaded drug is stably
      encapsulated until it enters the cancer cells owing to the noncovalently bound
      polymer gatekeeper. In the presence of polymer gatekeepers, the drug-loaded
      mesoporous silica nanoparticles showed enhanced colloidal stability. The
      simplicity of drug encapsulation allows any combination of small
      chemotherapeutics to be coencapsulated and thus produce synergetic therapeutic
      effects. The disulfide moiety facilitates decoration of the nanoparticles with
      cysteine containing ligands through thiol-disulfide chemistry under mild
      conditions. To show the versatility of drug targeting to cancer cells, we
      decorated the surface of the shell-cross-linked nanoparticles with two types of
      peptide ligands, SP94 and RGD. The nanocarriers reported here can release
      encapsulated drugs inside the reducing microenvironment of cancer cells via
      degradation of the polymer shell, leading to cell death. 

PMID- 26200586
TI  - Using Lopinavir Concentrations in Hair Samples to Assess Treatment Outcomes on
      Second-Line Regimens Among Asian Children.
AB  - We conducted a prospective monitoring study to determine whether antiretroviral
      (ARV) levels in hair of Asian children on second-line protease inhibitor-based
      ARV therapy (ART) are associated with virologic failure (VF), compared to plasma
      drug levels and self-reported adherence. HIV-infected Asian children on second
      line ART regimens were enrolled into a longitudinal cohort. Traditional adherence
      measures, plasma, and hair samples were collected 24 weeks after study
      enrollment. Hair ARV levels were determined via liquid chromatography/tandem mass
      spectrometry. Among 149 children on lopinavir/ritonavir-based regimens, 47% were
      female; the median [interquartile range (IQR)] age was 10.3 (7.9-13.3) years. The
      median CD4% was 26% (IQR 21.7-32.1%) and the median CD4 cell count 754 (IQR 596
      1,013) cells/mm(3). The median duration of lopinavir-based ART prior to week 24
      of the study was 2.9 (IQR 1.6-4.2) years. Adherence was >95% in 91% (135/148) by
      visual analogue scale and 89% (129/145) by pill count. The median lopinavir hair
      concentrations were 5.43 (IQR 3.21-9.01) ng/mg in children with HIV RNA >1,000
      copies/ml and 9.96 (IQR 6.51-12.31) ng/mg in children with HIV RNA <1,000
      copies/ml (p = 0.003). Plasma trough and lopinavir hair concentrations were not
      statistically significantly correlated (Pearson's correlation coefficient 0.20; p
      = 0.13). Increasing lopinavir hair concentrations in quartiles were strongly
      associated with virologic success (odds ratios >=4.0, overall p = 0.02), while
      self-reported adherence, pill count, and plasma lopinavir levels were not. Based
      on this first report of hair ARV concentrations and virologic outcomes in
      children, ARV hair concentrations, representing longer-term adherence, may be
      useful to identify children at risk for VF. 

PMID- 26200588
TI  - High-Frequency Repetitive Transcranial Magnetic Stimulation Effects on Motor
      Intracortical Neurophysiology: A Sham-Controlled Investigation.
AB  - PURPOSE: The purpose of this study was to investigate the effects of high
      frequency repetitive transcranial magnetic stimulation (rTMS) versus sham
      stimulation on intracortical inhibition (ICI) and intracortical facilitation
      within the motor cortex. Such data are needed to better understand the presumed
      neurophysiologic effects of rTMS. METHODS: The authors hypothesized that,
      compared with sham stimulation, 20 Hz rTMS will decrease ICI and increase
      intracortical facilitation in healthy volunteers. Using single-pulse and paired
      pulse TMS, the authors evaluated prestimulation and poststimulation effects on
      motor cortex neurophysiology in neurologically healthy volunteers who received
      2,000 stimuli of either 20 Hz rTMS (n = 11) or sham rTMS (n = 8). Primary
      outcomes were changes in ICI and intracortical facilitation and secondary
      outcomes were changes in motor threshold and motor evoked potential amplitude,
      and both were assessed using separate 2 * 2 (group * time) repeated-measures
      analysis of variance. RESULTS: For ICI, there were main effects of time (P =
      0.002) and group (P < 0.001) with a significant group-by-time interaction (P <
      0.01). Intracortical inhibition decreased after rTMS, but was unchanged by sham
      rTMS. Intracortical facilitation results revealed a main effect of group (P =
      0.02) and a significant group-by-time interaction (P = 0.048). Intracortical
      facilitation increased after rTMS and was slightly reduced after sham rTMS. The
      group-by-time interactions for motor threshold and motor evoked potential
      amplitude were not significant. CONCLUSIONS: High-frequency rTMS significantly
      influences the excitatory and inhibitory outputs of motor intracortical networks,
      specifically increasing intracortical facilitation and reducing ICI as compared
      with sham stimulation. Such changes were observed despite no significant changes
      in broader measures of motor cortex activation, that is, motor threshold and
      motor evoked potential amplitude.

PMID- 26200589
TI  - Cardiac Autonomic Response to Active Standing in Adults With Vasovagal Syncope.
AB  - PURPOSE: Little is known about the autonomic response to active standing in
      vasovagal syncope, and most works have focused on children or adolescents. The
      aim of this work was to study the changes in cardiac autonomic modulation in
      adult patients with vasovagal syncope through heart rate variability analysis
      with linear and short-term complexity (alpha-1) indexes during supine position
      and active standing, in patients with positive or negative head-up tilt test
      (HUTT). METHODS: Twenty-five patients with vasovagal syncope were included. Heart
      rate variability linear and short-term complexity (alpha-1) indexes were recorded
      during an active standing test (15 minutes in each position) and compared among
      patients grouped by HUTT outcome and between positions. RESULTS: During supine
      position, positive HUTT (+HUTT) patients had longer mean RR (1016 [850-1051]
      milliseconds), higher pNN50 (17.7 [9.2-26.2]), lower sympathovagal balance (1.3
      [0.5-1.7]), and alpha-1 (0.9 [0.8-1.0]) than negative HUTT (-HUTT) patients (871
      [776-969] milliseconds, 8.8 [2.1-14.5], 2.9 [1.3-3.9], and 1.2 [1.0-1.1],
      respectively). During active standing, heart rate and alpha-1 increased in both
      groups; in +HUTT patients, pNN50 decreased, whereas sympathovagal balance
      increased. The magnitude of change between positions of sympathovagal balance and
      alpha-1 was 6.1 and 4.8 times larger in +HUTT than -HUTT patients, respectively.
      CONCLUSIONS: The underlying cardiac autonomic mechanism in vasovagal syncope may
      involve different autonomic patterns in subjects with a history of recurrent
      syncope and +HUTT or -HUTT.

PMID- 26200590
TI  - Concerns About Utility and Cost-Effectiveness of Continuous Critical-Care EEG.

PMID- 26200591
TI  - Clinical Correlates and Prognostic Significance of Lateralized Periodic
      Discharges in Patients Without Acute or Progressive Brain Injury: A Case-Control
      Study.
AB  - PURPOSE: Lateralized periodic discharges (LPDs, also known as periodic
      lateralized epileptiform discharges) in conjunction with acute brain injuries are
      known to be associated with worse prognosis but little is known about their
      importance in absence of such acute injuries. We studied the clinical correlates
      and outcome of patients with LPDs in the absence of acute or progressive brain
      injury. METHODS: This is a case-control study of 74 patients with no acute brain
      injury undergoing continuous EEG monitoring, half with LPDs and half without,
      matched for age and etiology of remote brain injury, if any, or history of
      epilepsy. RESULTS: Lateralized periodic discharges were found in 145/1785 (8.1%)
      of subjects; 37/145 (26%) had no radiologic evidence of acute or progressive
      brain injury. Those with LPDs were more likely to have abnormal consciousness
      (86% vs. 57%; P = 0.005), seizures (70% vs. 24%; P = 0.0002), and functional
      decline (62% vs. 27%; P = 0.005), and were less likely to be discharged home (24%
      vs. 62%; P = 0.002). On multivariate analysis, LPDs and status epilepticus were
      associated with abnormal consciousness (P = 0.009; odds ratio = 5.2, 95% CI =
      1.60-20.00 and P = 0.017; odds ratio = 5.0, 95% CI = 1.4-21.4); and LPDs were
      independently associated with functional decline (P = 0.001; odds ratio = 4.8,
      95% CI = 1.6-15.4) and lower likelihood of being discharged home (P = 0.009; odds
      ratio = 0.2, 95% CI = 0.04-0.6). CONCLUSIONS: Despite absence of acute or
      progressive brain injury, LPDs were independently associated with abnormal
      consciousness and worse outcome at hospital discharge.

PMID- 26200592
TI  - The Timing of Continuous EEG in Critically Ill Patients Stat? ASAP? Routine?

PMID- 26200593
TI  - Heterometallic Second-Row Transition Metal Chain Compounds in Two Charge States:
      Syntheses, Properties, and Electronic Structures of [Mo-Mo-Ru](6+/7+) Chains.
AB  - Reaction of Mo2(dpa)4 (dpa = 2,2'-dipyridylamido) with (1)/2 equiv of
      [Ru(CO)3Cl2]2 in molten naphthalene at 250  degrees C provides facile access to
      the first all-second-row transition metal heterometallic chain compound,
      MoMoRu(dpa)4Cl2 (1). The one-electron oxidized compound [MoMoRu(dpa)4Cl2](OTf)
      (2) is synthesized by reaction of 1 with FeCp2(OTf). X-ray crystallography
      reveals a contraction of the Mo-Ru bond distance from 2.38 A in 1 to 2.30 A in 2,
      and an elongation of the Mo-Mo bond distance from 2.12 A in 1 to 2.21 A in 2. The
      short Mo-Ru bond distances indicate significant electron delocalization along the
      Mo-Mo-Ru chain, which is quantified by density functional theory (DFT)
      calculations. Molecular orbital analyses of both compounds based on DFT results
      reveal full delocalization of the orbitals of sigma and pi symmetry for both
      compounds. Additionally, delta orbital delocalization is observed in 2. 

PMID- 26200594
TI  - Some Important Deficiencies in the Development, Validation, and Reporting of a
      Prediction Model-Reply.

PMID- 26200595
TI  - Synthesis and Exciton Dynamics of Triplet Sensitized Conjugated Polymers.
AB  - We report the synthesis of a novel polythiophene-based host-guest copolymer
      incorporating a Pt-porphyrin complex (TTP-Pt) into the backbone for efficient
      singlet to triplet polymer exciton sensitization. We elucidated the exciton
      dynamics in thin films of the material by means of Transient Absorption
      Spectrosopcy (TAS) on multiple time scales and investigated the mechanism of
      triplet exciton formation. During sensitization, singlet exciton diffusion is
      followed by exciton transfer from the polymer backbone to the complex where it
      undergoes intersystem crossing to the triplet state of the complex. We directly
      monitored the triplet exciton back transfer from the Pt-porphyrin to the polymer
      and found that 60% of the complex triplet excitons were transferred with a time
      constant of 1087 ps. We propose an equilibrium between polymer and porphyrin
      triplet states as a result of the low triplet diffusion length in the polymer
      backbone and hence an increased local triplet population resulting in increased
      triplet-triplet annihilation. This novel system has significant implications for
      the design of novel materials for triplet sensitized solar cells and upconversion
      layers. 

PMID- 26200596
TI  - Repetitive obidoxime treatment induced increase of red blood cell
      acetylcholinesterase activity even in a late phase of a severe methamidophos
      poisoning: A case report.
AB  - Accidental self-poisoning or deliberate use in suicidal intent of
      organophosphorus pesticides (OPP), which are widely used in agriculture,
      represent a health problem worldwide. Symptoms of poisoning are characterized by
      acute cholinergic crisis caused by inhibition of acetylcholinesterase. A 75-year
      old male patient ingested 20ml of an OPP solution containing 10% methamidophos in
      suicidal intent. In the course of poisoning typical clinical symptoms of
      cholinergic crisis (miosis, bradycardia, hypotension, hypersalivation and
      impairment of neurologic status) were evident. Butyryl (plasma) cholinesterase
      (BChE) and red blood cell acetylcholinesterase (RBC-AChE) revealed decreased
      activities, thus specific treatment with the enzyme reactivator obidoxime was
      started. Inhibitory activity of the patient's plasma indicated significant
      amounts of persisting methamidophos in the circulation and was still found on day
      4 after ingestion. Due to missing spontaneous breathing on day 6, obidoxime was
      administered again. Afterwards a significant increase of RBC-AChE activity was
      found. The patient was extubated on day 10 and a restitution ad integrum was
      achieved. In conclusion, obidoxime is a potent reactivator of OPP-inhibited AChE.
      A repetitive and prolonged administration of obidoxime should be considered in
      cases of severe methamidophos poisoning and should be tailored with an advanced
      analytical biomonitoring. 

PMID- 26200597
TI  - A commentary on "The effectiveness of oxygen therapy in carbon monoxide poisoning
      is pressure- and time-dependent: A study on cultured astrocytes".

PMID- 26200598
TI  - Mechanisms of CDDO-imidazolide-mediated cytoprotection against acrolein-induced
      neurocytotoxicity in SH-SY5Y cells and primary human astrocytes.
AB  - Acrolein is a ubiquitous unsaturated aldehyde has been implicated in the
      pathogenesis of various neurological disorders. However, limited study has been
      conducted into potential therapeutic protection and underlying mechanism against
      acrolein-induced cytotoxicity via upregulation of cellular aldehyde
      detoxification defenses. In this study we have utilized RA-differentiated human
      SH-SY5Y cells and primary human astrocytes to investigate the induction of
      glutathione (GSH) by the synthetic triterpenoid 2-cyano-3,12-dixooleana-1,9-dien
      28-imidazolide (CDDO-Im) and the protective effects CDDO-Im-mediated antioxidant
      defenses on acrolein toxicity. Acrolein exposure to RA-differentiated SH-SY5Y
      cells resulted in a significant time dependent depletion of cellular GSH
      preceding a reduction in cell viability and LDH release. Further, we demonstrated
      the predominance of cellular GSH in protection against acrolein-induced
      cytotoxicity. Buthionine sulfoximine (BSO) at 25MUM dramatically depleted GSH and
      significantly potentiated acrolein-induced cytotoxicity. Pretreatment of the
      cells with 100nM CDDO-Im afforded a dramatic protection against acrolein-induced
      cytotoxicity. Pretreatment of BSO and CDDO was found to prevent the CDDO-Im
      mediated GSH induction and partially reversed the cytoprotective effects of CDDO
      Im against acrolein cytotoxicity. Overall, this study represents for the first
      time the CDDO-Im mediated upregulation of GSH is a predominant mechanism against
      acrolein-induced neurotoxicity. 

PMID- 26200600
TI  - Catalytic bioscavengers in nerve agent poisoning: A promising approach?
AB  - The repeated use of the nerve agent sarin against civilians in Syria in 2013
      emphasizes the continuing threat by chemical warfare agents. Multiple studies
      demonstrated a limited efficacy of standard atropine-oxime treatment in nerve
      agent poisoning and called for the development of alternative and more effective
      treatment strategies. A novel approach is the use of stoichiometric or catalytic
      bioscavengers for detoxification of nerve agents in the systemic circulation
      prior to distribution into target tissues. Recent progress in the design of
      enzyme mutants with reversed stereo selectivity resulting in improved catalytic
      activity and their use in in vivo studies supports the concept of catalytic
      bioscavengers. Yet, further research is necessary to improve the catalytic
      activity, substrate spectrum and in vivo biological stability of enzyme mutants.
      The pros and cons of catalytic bioscavengers will be discussed in detail and
      future requirements for the development of catalytic bioscavengers will be
      proposed. 

PMID- 26200599
TI  - Exposure to p,p'-DDE enhances differentiation of 3T3-L1 preadipocytes in a model
      of sub-optimal differentiation.
AB  - The incidence of obesity is increasing worldwide at an alarming rate. Recently,
      exposure to environmental contaminants, especially organochlorines such as p,p'
      dichlorodiphenyldichloroethylene (DDE), has been implicated as a possible
      causative factor in the increasing obesity epidemic. The objective of this study
      was to evaluate the ability of DDE to alter adipogenesis in a model of sub
      optimal differentiation. 3T3-L1 preadipocytes were induced to differentiate in
      the presence of DDE (0.01-100MUM) using a sub-optimal differentiation cocktail.
      Eight days after the initiation of differentiation, adipogenesis was assessed
      through neutral lipid staining, triglyceride accumulation, and expression of
      markers of terminal differentiation. Exposure to DDE induced a concentration
      dependent increase in intracellular neutral lipid accumulation as determined by
      Oil Red O staining and triglyceride assay. Alterations in lipid accumulation were
      accompanied by upregulation of genetic markers of differentiation. DDE (10MUM)
      enhanced expression of fatty acid binding protein 4 and Sterol regulatory element
      binding protein-1c at the 2.5 and 20MUM concentrations. DDE (2.5, 10, and 20MUM)
      induced upregulation of leptin and fatty acid synthase, as compared to sub
      optimal vehicle control (0.05% ethanol). Our results indicate that DDE is capable
      of enhancing adipogenesis and intracellular lipid accumulation in 3T3-L1 cells
      through upregulation of molecular targets responsible for lipid storage. 

PMID- 26200601
TI  - Monitoring Vascular Disrupting Therapy in a Rabbit Liver Tumor Model:
      Relationship between Tumor Perfusion Parameters at IVIM Diffusion-weighted MR
      Imaging and Those at Dynamic Contrast-enhanced MR Imaging.
AB  - PURPOSE: To investigate whether perfusion-related intravoxel incoherent motion
      (IVIM) diffusion-weighted (DW) magnetic resonance (MR) imaging parameters
      correlate with dynamic contrast material-enhanced MR imaging parameters in
      between-subject and/or within-subject longitudinal settings for monitoring the
      therapeutic effects of a vascular disrupting agent (VDA) (CKD-516) in rabbit VX2
      liver tumors. MATERIALS AND METHODS: With institutional Animal Care and Use
      Committee approval, 21 VX2 liver tumor-bearing rabbits (treated, n = 15; control,
      n = 6) underwent IVIM DW imaging with 12 b values (0-800 sec/mm(2)) and dynamic
      contrast-enhanced MR imaging performed before (baseline) CKD-516 administration
      and 4 hours, 24 hours, and 7 days after administration. Perfusion-related IVIM DW
      imaging parameters of the tumors, including the pseudodiffusion coefficient (D*)
      and perfusion fraction (f), as well as dynamic contrast-enhanced MR imaging
      parameters, including the volume transfer coefficient (K(trans)) and initial area
      under the gadolinium concentration-time curve until 60 seconds (iAUC), were
      measured. IVIM DW imaging parameters were correlated with dynamic contrast
      enhanced MR imaging parameters by using Pearson correlation analysis between
      subjects at each given time and by using a linear mixed model for within-subject
      longitudinal data. RESULTS: In the treated group, D*, f, K(trans), and iAUC
      significantly decreased (-40.7% to -26.3%) at 4-hour follow-up compared with
      these values in the control group (-6.9% to +5.9%) (P < .05). For longitudinal
      monitoring of CKD-516 treatment, D* and f showed significant positive
      correlations with K(trans) and iAUC (P = .004 and P = .02; P < .001 and P = .006,
      respectively), while no significant correlations were observed between IVIM DW
      imaging and dynamic contrast-enhanced MR imaging parameters between subjects at
      any given time (P > .05). CONCLUSION: In a rabbit tumor model, perfusion
      parameters serially quantified with IVIM DW imaging can be used as alternatives
      to dynamic contrast-enhanced MR imaging parameters in reflecting the dynamic
      changes in tumor perfusion during the within-subject longitudinal monitoring of
      VDA treatment.

PMID- 26200603
TI  - Brain Default Mode Network Changes after Renal Transplantation: A Diffusion
      Tensor Imaging and Resting-State Functional MR Imaging Study.
AB  - PURPOSE: To investigate structural and functional alterations of the default mode
      network (DMN) in the brain after renal transplantation in patients with end-stage
      renal disease by using diffusion-tensor imaging and resting-state functional MR
      imaging. MATERIALS AND METHODS: This prospective study was approved by the local
      medical research ethics committee, and written informed consent was obtained.
      Twenty-one patients with end-stage renal disease (15 men, six women; mean age +/-
      standard deviation, 32 years +/- 9.5) who were scheduled to undergo renal
      transplantation and 21 healthy control subjects (15 men, six women; mean age, 31
      years +/- 6.5) were included. Diffusion-tensor imaging and resting-state
      functional MR imaging were performed in all subjects. Patients were imaged both
      before and 1 month after renal transplantation. Structural (mean diffusivity,
      fractional anisotropy, path length, and number of tracts derived from diffusion
      tensor imaging tractography) and functional (temporal correlation coefficient
      derived from resting-state functional MR imaging) connectivity of the DMN were
      quantitatively compared with two-sample t tests or paired t tests. Intergroup
      correlation analysis was performed to compare structural or functional indexes
      and results of neuropsychological or blood biochemistry tests. RESULTS: Mean
      diffusivity was decreased in the fiber bundles connecting the posterior cingulate
      cortex and the precuneus to the bilateral inferior parietal lobules in patients
      after renal transplantation compared with that in patients before transplantation
      (P < .05). Temporal correlation coefficients for patients after renal
      transplantation nearly reached the levels of those for control subjects (all, P >
      .05). The change in mean diffusivity of the fiber bundles connecting the
      posterior cingulate cortex and the precuneus to the right inferior parietal
      lobule positively correlated with the change in hematocrit levels (r = 0.522, P =
      .015), the change in temporal correlation coefficients between the posterior
      cingulate cortex or precuneus and left or right inferior parietal lobules
      correlated with changes in number connection test type A scores (r = -0.549, P =
      .010) and digit symbol test scores (r = 0.533, P = .013). CONCLUSION: Functional
      connectivity changes in the DMN, which were associated with improved hematocrit
      levels and cognitive function, may recover earlier than structural connectivity
      changes do 1 month after renal transplantation.

PMID- 26200604
TI  - Comparison of the disease activity score using the erythrocyte sedimentation rate
      and C-reactive protein levels in Koreans with rheumatoid arthritis.
AB  - OBJECTIVE: The Disease Activity Score based on 28 joints (DAS28) has been widely
      used in clinical practice and research studies of rheumatoid arthritis (RA). The
      objective of this study was to evaluate the discordance in the DAS28 based on the
      erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) levels in
      Korean patients with RA. METHODS: From August to December 2011, 540 patients with
      RA who visited two rheumatology clinics affiliated with Hallym University (Korea)
      and had at least one DAS28 evaluation were examined. RESULTS: The mean age of the
      included patients was 53 years, and 82% were female. The mean duration of disease
      was 32.9 +/- 41.2 months. The mean DAS28-ESR was higher than the DAS28-CRP (3.65
      vs. 3.44; P < 0.001). In the DAS28-ESR group, 126 patients (23.3%) satisfied the
      criteria for remission versus 134 (24.8%) in the DAS28-CRP group. High disease
      activity was determined in 80 (14.8%) patients in the DAS28-ESR group and in 43
      (8.0%) in the DAS28-CRP group. A comparison of the two groups with respect to
      four DAS28 disease activity categories showed agreement in 344 patients (63.7%;
      kappa = 0.45). In classifying patients as European League Against Rheumatism
      (EULAR) responders, agreement between the two methods was shown in 56 patients
      (71.8%; kappa = 0.76). When disagreements between the two scores occurred, more
      patients had a better EULAR response based on the DAS28-ESR than on the DAS28-CRP
      (19.2% vs. 8.9%, respectively). CONCLUSION: The discordance between the ESR-based
      and CRP-based DAS28 could affect clinical treatment decisions for patients with
      RA.

PMID- 26200602
TI  - Comprehensive Assessment of Osteoporosis and Bone Fragility with CT Colonography.
AB  - PURPOSE: To evaluate the ability of additional analysis of computed tomographic
      (CT) colonography images to provide a comprehensive osteoporosis assessment.
      MATERIALS AND METHODS: This Health Insurance Portability and Accountability Act
      compliant study was approved by our institutional review board with a waiver of
      informed consent. Diagnosis of osteoporosis and assessment of fracture risk were
      compared between biomechanical CT analysis and dual-energy x-ray absorptiometry
      (DXA) in 136 women (age range, 43-92 years), each of whom underwent CT
      colonography and DXA within a 6-month period (between January 2008 and April
      2010). Blinded to the DXA data, biomechanical CT analysis was retrospectively
      applied to CT images by using phantomless calibration and finite element analysis
      to measure bone mineral density and bone strength at the hip and spine.
      Regression, Bland-Altman, and reclassification analyses and paired t tests were
      used to compare results. RESULTS: For bone mineral density T scores at the
      femoral neck, biomechanical CT analysis was highly correlated (R(2) = 0.84) with
      DXA, did not differ from DXA (P = .15, paired t test), and was able to identify
      osteoporosis (as defined by DXA), with 100% sensitivity in eight of eight
      patients (95% confidence interval [CI]: 67.6%, 100%) and 98.4% specificity in 126
      of 128 patients (95% CI: 94.5%, 99.6%). Considering both the hip and spine, the
      classification of patients at high risk for fracture by biomechanical CT analysis
      -those with osteoporosis or "fragile bone strength"--agreed well against
      classifications for clinical osteoporosis by DXA (T score <=-2.5 at the hip or
      spine), with 82.8% sensitivity in 24 of 29 patients (95% CI: 65.4%, 92.4%) and
      85.7% specificity in 66 of 77 patients (95% CI: 76.2%, 91.8%). CONCLUSION:
      Retrospective biomechanical CT analysis of CT colonography for colorectal cancer
      screening provides a comprehensive osteoporosis assessment without requiring
      changes in imaging protocols.

PMID- 26200605
TI  - Targeted approaches and innovative illumination solutions: A new era for
      photodynamic therapy applications in gynecologic oncology?

PMID- 26200606
TI  - Assessment of the specificity of a new folate-targeted photosensitizer for
      peritoneal metastasis of epithelial ovarian cancer to enable intraperitoneal
      photodynamic therapy. A preclinical study.
AB  - BACKGROUND: Ovarian cancer's prognosis remains dire after primary therapy.
      Recurrence rate is disappointingly high as 60% of women with epithelial ovarian
      cancer considered in remission will develop recurrent disease within 5 years.
      Special attention to undetected peritoneal metastasis during surgery is necessary
      as they are the main predictive factors of recurrences. Folate Receptor alpha
      (FRalpha) shows promising prospects in targeting ovarian cancerous cells and
      intraperitoneal photodynamic therapy (PDT) could be a solution in addition to
      macroscopic cytoreductive surgery to treat peritoneal micrometastasis. The aim of
      this preclinical study is to assess the specificity of a folate-targeted
      photosensitizer for ovarian peritoneal micrometastasis. METHODS: We used the NuTu
      19 epithelial ovarian cancer cell line to induce peritoneal carcinomatosis in
      female Fischer 344 rats. Three groups of 6 rats were studied (Control (no
      photosensitizer)/Non-conjugated photosensitizer (Porph)/Folate-conjugated
      photosensitizer (Porph-s-FA)). Four hours after the administration of the
      photosensitizer, animals were sacrificed and intraperitoneal organs tissues were
      sampled. FRalpha tissue expression was evaluated by immunohistochemistry. Tissue
      incorporation of photosensitizers was assessed by confocal microscopy and tissue
      quantification. RESULTS: FRalpha is overexpressed in tumor, ovary, and liver
      whereas, peritoneum, colon, small intestine, and kidney do not express it.
      Cytoplasmic red endocytosis vesicles observed by confocal microscopy are well
      correlated to FRalpha tissue expression. Photosensitizer tissue quantification
      shows a mean tumor-to-normal tissue ratio of 9.6. CONCLUSION: We demonstrated
      that this new generation folate-targeted photosensitizer is specific of
      epithelial ovarian peritoneal metastasis and may allow the development of
      efficient and safe intraperitoneal PDT procedure.

PMID- 26200607
TI  - Induction of apoptosis in HPV16 E7 transfected human keratinocyte by ALA-mediated
      photodynamic therapy.
AB  - BACKGROUND AND OBJECTIVE: 5-Aminolevulinic acid (ALA)-mediated photodynamic
      therapy (ALA-PDT) is effective for the treatment of condyloma and intraepithelial
      neoplasia associated with human papillomaviruses (HPV). However, the mechanism of
      PDT on HPV-infected host cells is not fully understood. The aim of this in vitro
      study was to examine ALA-PDT induced apoptosis in a high-risk HPV E7 gene
      transfected cell line. MATERIALS AND METHODS: HPV16 E7 gene obtained from HPV16
      positive human cervical carcinoma was transfected into a human keratinocyte cell
      line. PpIX generation and ALA-PDT-induced apoptosis and mitochondrial damage were
      investigated in vitro. RESULTS: Fluorescence examination showed that HPV16E7
      transfected cells could produce PpIX fairly quickly in the presence of 1mM ALA.
      Apoptosis occurred after ALA-PDT at dose levels of 4, 8, and 12 J/cm(2).
      Mitochondrial potential collapse occurred as early as 2 h post PDT. ALA-PDT
      induced a relatively weak and shorter caspase-9 activation but a strong and long
      lasting caspase-3 activation. However, mRNA levels of caspase-9 and -3 genes in
      cells treated with ALA-PDT were unchanged. CONCLUSION: This in vitro study
      demonstrated that HPV16 E7 transfected keratinocytes could generate PpIX in the
      presence of ALA. Under light irradiation, ALA-PDT could induce mitochondrial
      dependent apoptosis in HPV16 E7 transfected cells.

PMID- 26200608
TI  - Older Adults and Unanticipated Hospital Admission within 30 Days of Ambulatory
      Surgery: An Analysis of 53,667 Ambulatory Surgical Procedures.
AB  - OBJECTIVES: To evaluate whether age is independently associated with greater rate
      of unanticipated hospital admission within 30 days of ambulatory surgery. DESIGN:
      Retrospective database study. SETTING: The 2012 National Surgical Quality
      Improvement Project data set. PARTICIPANTS: All individuals with "outpatient"
      recorded as their status in the data set. MEASUREMENTS: The primary outcome of
      interest was all-cause hospital admission in the 30-day period after surgery.
      Multivariate models were constructed to control for covariate bias. Assessment of
      interactions of terms in the final model was performed using a conditional tree
      analysis. RESULTS: The final analysis included 53,667 ambulatory surgical cases.
      There were 1,370 (2.5%, 99% confidence interval (CI) = 2.4-2.7%) hospital
      admissions among the cases evaluated. After adjusting for potential confounders,
      age (<70 vs >=70) was independently associated with hospital admission (odds
      ratio = 1.54, 99% CI = 1.29-1.84). A classification tree analysis of the cases
      without postoperative morbidity identified age (<60 vs >=60) as an important
      decision point leading to greater likelihood of admission (P < .001) within 30
      days after ambulatory surgery. CONCLUSION: Even after adjusting for
      comorbidities, older adults are at greater risk of unanticipated hospital
      admission within 30 days of ambulatory surgery. Renal failure, chronic
      obstructive pulmonary disease, current cancer treatment, diabetes mellitus, and
      history of amputation or revascularization were also associated with greater
      likelihood of hospital admission. Interventions to improve transitions of care
      for older adults after ambulatory surgery are needed.

PMID- 26200610
TI  - Diagnostic Ability of FDG-PET/CT in the Detection of Malignant Pleural Effusion.
AB  - We investigated the role of F-18 fluorodeoxyglucose (FDG)-positron emission
      tomography (PET)/computed tomography (CT) for the differential diagnosis of
      malignant and benign pleural effusion. We studied 36 consecutive patients with
      histologically proven cancer (excluding malignant mesothelioma) who underwent FDG
      PET/CT for suspected malignant pleural effusion. Fourteen patients had
      cytologically proven malignant pleural effusion and the other 22 patients had
      either negative cytology or clinical follow-up, which confirmed the benign
      etiology. We examined the maximum standardized uptake values (SUV max) of pleural
      effusion and the target-to-normal tissue ratio (TNR), calculated as the ratio of
      the pleural effusion SUV max to the SUV mean of the normal tissues (liver,
      spleen, 12th thoracic vertebrae [Th12], thoracic aorta, and spinalis muscle). We
      also examined the size and density (in Hounsfield units) of the pleural effusion
      and pleural abnormalities on CT images. TNR (Th12) and increased pleural FDG
      uptake compared to background blood pool were significantly more frequent in
      cases with malignant pleural effusion (P < 0.05 for both). The cutoff TNR (Th12)
      value of >0.95 was the most accurate; the sensitivity, specificity, and accuracy
      for this value were 93%, 68%, and 75%, respectively. FDG-PET/CT can be a useful
      method for the differential diagnosis of malignant and benign pleural effusion.

PMID- 26200611
TI  - Symmetrical Curvilinear Cytotoxic Edema Along the Surface of the Brain Stem: A
      Probable New Magnetic Resonance Imaging Finding of Leptomeningeal Carcinomatosis.
AB  - Lung cancer is one of the most common neoplasms to appear leptomeningeal
      metastasis (LM). Contrast-enhanced magnetic resonance imaging (MRI) is better
      diagnostic choice for LM and usually shows focal nodular or diffuse linear
      enhancement on the leptomeninges along the sulci and tentorium in the brain. We
      experienced atypical 2 cases of lung cancer in patients who showed unusual brain
      MRI finding of symmetrical curvilinear or band-like, nonenhancing cytotoxic edema
      along the surface of the brain stem. This finding is unique and different from
      the general findings of leptomeningeal metastasis. This unique imaging finding of
      symmetric curvilinear nonenhancing cytotoxic edema along the brainstem is
      extremely rare and represents a new presentation of leptomeningeal
      carcinomatosis.

PMID- 26200612
TI  - Postoperative Complications After Prophylactic Thyroidectomy for Very Young
      Patients With Multiple Endocrine Neoplasia Type 2: Retrospective Cohort Analysis.
AB  - The aim of this study was to investigate whether younger age at surgery is
      associated with the increased incidence of postoperative complications after
      prophylactic thyroidectomy in pediatric patients with multiple endocrine
      neoplasia (MEN) 2. The shift toward earlier thyroidectomy has resulted in
      significantly less medullary thyroid carcinoma (MTC)-related morbidity and
      mortality. However, very young pediatric patients might have a higher morbidity
      rate compared with older patients. Hardly any literature exists on complications
      in the very young. A retrospective single-center analysis was performed on the
      outcomes of MEN2 patients undergoing a prophylactic total thyroidectomy at the
      age of 17 or younger. Forty-one MEN2A and 3 MEN2B patients with thyroidectomy
      after January 1993 and at least 6 months of follow-up were included, subdivided
      in 9 patients younger than 3 years, 15 patients 3 to 6 years, and 20 patients
      older than 6 years. Postoperative hypocalcemia and other complications were
      registered. Twelve (27%) patients developed transient hypocalcemia and 9 (20%)
      patients suffered from permanent hypocalcemia, with a nonsignificant trend toward
      higher incidence with decreasing age. Three (7%) patients had other
      complications, of whom 2 were younger than 3 years. For patients younger than 3
      years, the average length of stay (LOS) was 6.7 days, versus 1.7 and 3.5 days,
      respectively, for the older patient groups (P < 0.05). Patients with
      complications had a longer LOS compared with patients without (5.0 vs 2.0, P <
      0.01). None of the patients had clinical signs of recurrent MTC after a mean
      follow-up of 10.5 years. Prophylactic thyroidectomy in very young children is
      associated with a higher rate of complications, causing a significant increased
      LOS. Irrespective age of surgery, MTC did not recur in any patient. In planning
      optimal timing of surgery, clinicians should take the risk of complications into
      account. We advise not to perform total thyroidectomy before the age of 3 for
      patients defined high risk by the American Thyroid Association guideline.

PMID- 26200613
TI  - Relationship Between Tei Index and PEP-Derived Myocardial Performance Index in
      Sinus Rhythm.
AB  - The goal of this study was to evaluate the preejection time (PEP)-derived
      myocardial performance index (MPI) in hypertensive (HT) patients with sinus
      rhythm and its relationship to the classic Tei index. One hundred five patients
      were enrolled in the study (65 HT and 40 control subjects). The mean age of all
      patients was 50.5 +/- 15 years and 60% were female. Echocardiography was
      performed on all patients. MPI was measured with the classic Tei method (MPI-Tei
      index) and the PEP-derived MPI method by using tissue Doppler echocardiography.
      Although the MPI-Tei index is defined as the ratio of isovolumetric contraction
      time (IVCT) along with isovolumetric relaxation time (IVRT) to ejection time
      (ET), PEP-derived MPI is defined as the ratio of PEP and IVRT to ET. We compared
      echocardiographic data between the HT group and the control group. MPI-Tei index
      and the PEP-derived MPI values were higher in the HT group compared with controls
      (0.52 +/- 0.10 vs 0.39 +/- 0.07, P < 0.001, and 0.51 +/- 0.09 vs 0.39 +/- 0.07).
      PEP-derived MPI was strongly correlated with the MPI-Tei index (r = 0.945, P <
      0.001). Our study determined that the PEP-derived MPI might be used in the
      evaluation of left ventricular function in patients with HT, similar to the
      classic MPI-Tei index.

PMID- 26200614
TI  - Molecular Analyses Define Valpha7.2-Jalpha33+ MAIT Cell Depletion in HIV
      Infection: A Case-Control Study.
AB  - Mucosal-associated invariant T (MAIT) cells are an abundant antibacterial innate
      like lymphocyte population. There are conflicting reports as to their fate in HIV
      infection. The objective of this study was to determine whether MAIT cells are
      truly depleted in HIV infection. In this case-control study of HIV-positive
      patients and healthy controls, quantitative real-time polymerase chain reaction
      was used to assess the abundance of messenger RNA (mRNA) and genomic DNA (gDNA)
      encoding the canonical MAIT cell T cell receptor (Valpha7.2-Jalpha33). Comparison
      was made with flow cytometry. Significant depletion of both Valpha7.2-Jalpha33
      mRNA and gDNA was seen in HIV infection. Depletion of Valpha7.2+CD161++ T cells
      was confirmed by flow cytometry. In HIV infection, the abundance of Valpha7.2
      Jalpha33 mRNA correlated most strongly with the frequency of Valpha7.2+CD161++
      cells. No increase was observed in the frequency of Valpha7.2+CD161- cells among
      CD3+CD4- lymphocytes. MAIT cells are depleted from blood in HIV infection as
      confirmed by independent assays. Significant accumulation of a CD161- MAIT cell
      population is unlikely. Molecular approaches represent a suitable alternative to
      flow cytometry-based assays for tracking of MAIT cells in HIV and other settings.

PMID- 26200615
TI  - Spontaneous Thoracic Curve Correction After Selective Posterior Fusion of
      Thoracolumbar/Lumbar Curves in Lenke 5C Adolescent Idiopathic Scoliosis.
AB  - Selective fusion of the thoracolumbar/lumbar (TL/L) curve is an effective method
      for the treatment of Lenke type 5C curves. Several studies have demonstrated that
      spontaneous correction of the thoracic curve does indeed occur. However, how this
      correction occurs after isolated posterior segmental instrumentation of the
      structural lumbar curve has not been well described. The aim of this study was to
      evaluate the response of the thoracic curve to selective TL/L curve fusion in
      patients with Lenke type 5C adolescent idiopathic scoliosis (AIS) and assess the
      correlative clinical outcomes. Thirty-four consecutive patients with Lenke type
      5C AIS were included in this study. All patients underwent selective TL/L curve
      instrumentation and fusion via the posterior approach. Coronal and sagittal
      radiographs were analyzed before surgery, at 1 week after surgery and at least 2
      years after surgery. The preoperative coronal Cobb angle of the major TL/L curve
      was 45.4 degrees  +/- 7.0 degrees , and that of the minor thoracic curve was 25.4
      degrees  +/- 8.8 degrees . The major TL/L and minor thoracic curves were
      corrected to postoperative angles of 9.5 degrees  +/- 5.0 degrees  and 11.2
      degrees  +/- 5.2 degrees , respectively, and measured 10.5 degrees  +/- 6.0
      degrees  and 13.4 degrees  +/- 7.5 degrees  at the follow-up, respectively. The
      supine side-bending average Cobb angle of the thoracic curve was 9.9 degrees .
      These results demonstrate satisfactory improvements because of coronal and
      sagittal restoration. Significant correlations were found between the
      preoperative and early postoperative conditions and the Cobb angle changes of the
      minor thoracic curve and the major TL/L curves (r = 0.42, P = 0.01). Significant
      correlations were also observed between the early and final follow-up
      postoperative conditions and the Cobb angle changes of the minor thoracic curve
      and the major TL/L curves (r = 0.57, P < 0.001). Significant correlations were
      observed between increased thoracic kyphosis (TK) and increased lumbar lordosis
      (LL) in the preoperative and early postoperative conditions (r = 0.36, P = 0.035)
      and between increased TK and increased LL in the preoperative and final follow-up
      postoperative conditions (r = 0.51, P = 0.002). Spontaneous correction of the
      thoracic curve is a reflection of the TL/L curve correction in Lenke 5C AIS
      patients. Supine side-bending radiographs are an effective method of predicting
      the spontaneous correction of thoracic curves. The correction of LL is important
      for maintaining spinal sagittal alignment.

PMID- 26200616
TI  - The Development and Validation of Hundred Paisa Pain Scale for Measuring
      Musculoskeletal Pain: A Prospective Observational Study.
AB  - The reduction in the pain intensity is one of the most important outcome measures
      in musculoskeletal disorders. The assessment of pain required reliable and valid
      scale. The aims of this prospective observational study were to develop and
      evaluate concurrent validity and test-retest reliability of hundred paisa pain
      scale (HPPS) for measuring musculoskeletal pain. A consecutive 74 patients with
      musculoskeletal pain with a wide variety of diagnoses were enrolled. Patients
      reported their intensity of pain on the following scale: HPPS, "visual analog
      scale (VAS)," and "numerical rating scale (NRS)." Patients were asked to complete
      another HPPS, VAS, and NRS after 2 days to determine the reproducibility of the
      scales. Spearman rank correlation coefficients between the HPPS and the NRS, and
      VAS were used to determine the validity of the scales. The correlation between
      the change score of HPPS, VAS, and NRS was used to determine the responsiveness
      of HPPS. Results of test-retest indicate that the reproducibility of HPPS was
      good to excellent with the intraclass correlation coefficient (ICC) value of 0.85
      (95% confidence interval [CI], 0.76-0.91). The standard error of measurement
      (SEM) was 5.24. The minimum detectable change based on the SEM for test-retest
      was 14.52. The reproducibility of VAS is moderate to good with the ICC value of
      0.82 (95% CI, 0.72-0.88). The reproducibility of NRS is good to excellent with
      the ICC value of 0.88 (95% CI, 0.81-0.92). There was a strong correlation between
      the HPPS and the VAS, and NRS (P < 0.01), which confirm the validity. The HPPS
      was responsive as the correlation of the change score of HPPS with the change
      score of VAS, and NRS were good (0.80 and 0.86, respectively). The HPPS is a
      valid and reliable scale to assess musculoskeletal pain, with psychometric
      properties in agreement with other comparable scale.

PMID- 26200617
TI  - Central Pancreatectomy as a Good Solution in Frantz Tumor Resection: A Case
      Report.
AB  - Solid pseudopapillary tumors of the pancreas located in the head or body are a
      challenging clinical problem because they usually demand extensive surgical
      procedures, and in most reported cases pancreaticoduodenectomy is the operation
      of choice in such a location. An alternative method of surgery in precisely
      selected patients is a procedure known as central pancreatectomy. The authors
      present the case of a 13-year-old girl with a 5 cm tumor located in the body of
      the pancreas. The favorable anatomical location of the tumor suggested central
      pancreatic resection. The tumor was excised with 1 cm oncologic margins from both
      sides, and the distal remnant of the pancreas was protected with a Roux-en-Y
      loop. In the postoperative period the patient required reoperation because of
      intensive bleeding in the resection site but the duodenal loop was saved and the
      patient protected from biliary tract reconstruction and exocrine and endocrine
      insufficiency. Progress in pancreatic surgery, especially in children, allows
      less radical options for the reason that preservation of endocrine and exocrine
      function is very important and protects them, especially from insulin-dependent
      diabetes in the future.

PMID- 26200618
TI  - Study of the Histopathologic Characteristics and Surface Morphologies of Glottic
      Carcinomas With Anterior Vocal Commissure Involvement.
AB  - This article explores the features and the role of the anterior vocal commissure
      (AVC) structure and the surface morphologies of glottic carcinomas with AVC
      involvement to provide a reference for the selection of transoral carbon dioxide
      (CO2) laser surgery. A total of 31 cases of glottic carcinomas with AVC
      involvement from May 2012 to January 2014 were included. All patients underwent
      electronic laryngoscopic examinations and computed tomography scans to determine
      the surface morphology. After surgery, the tumor specimens were resected
      integrally, and axial serial sections parallel to the plane of vocal cords were
      taken to explore the features and possible invasion paths of the glottic
      carcinomas with AVC involvement. The rates of involvement of the supraglottis and
      subglottis were 71.4% and 14.8%, respectively, via the AVC. The involvement of
      the superficial layer of the unilateral or bilateral vocal cords without
      involvement of the vocal muscle in the AVC region (IVM) or the cartilage was
      present in 15 cases (48.4%). The involvement of the superficial layer of the
      unilateral and bilateral vocal cords occurred in 16 cases (51.6%) with the IVM in
      13 cases and the involvement of the intermediate lamina of the thyroid cartilage
      (ITC) in 8 cases. The involvement of the ITC was associated with the involvement
      of the vocal muscle of the AVC region (P < 0.05). Among the pushing carcinomas,
      15 of 21 (71.4%) presented with well-defined tumor mass, and 8 of 10 (80.0%)
      infiltrating carcinomas presented with multiple tumor nests that were often
      surrounded by fibrosis (P < 0.05). The AVC is an important path of invasion of
      subglottic in glottic carcinomas but less so for suparglottic. The Broyles'
      ligaments acted as a barrier against the spread of the tumors to the thyroid
      cartilage, but this role was obviously weaken by the involvement of the vocal
      muscle of the AVC region. The infiltrating carcinomas presented with multiple
      tumor nests in fibrous tissue. When CO2 laser microsurgery is considered as a
      treatment option, these facts should be kept in mind.

PMID- 26200620
TI  - Retrospective, Demographic, and Clinical Investigation of the Causes of
      Postoperative Infection in Patients With Lumbar Spinal Stenosis Who Underwent
      Posterior Stabilization.
AB  - Owing to the increasing population of elderly patients, a large number of
      patients with degenerative spondylosis are currently being surgically treated.
      Although basic measures for decreasing postoperative surgical infections (PSIs)
      are considered, it still remains among the leading causes of morbidity and
      mortality. The aim of this retrospective analysis is to present possible causes
      leading to PSI in patients who underwent surgery for lumbar degenerative
      spondylosis and highlight how it can be avoided to decrease morbidity and
      mortality. The study included 540 patients who underwent posterior stabilization
      due to degenerative lumbar stenosis between January 2013 and January 2014. The
      data before and after surgery was retrieved from the hospital charts. Patients
      with degenerative lumbar stenosis who were operated upon in this study had >2
      levels of laminectomy and facetectomy. For this reason, posterior stabilization
      was performed for all the patients included in this study. Determining the causes
      of postoperative infection (PI) following spinal surgeries performed with
      instrumentation is a struggle. Seventeen different parameters that may be related
      to PI were evaluated in this study. The presence of systemic diseases, unknown
      glove perforations, and perioperative blood transfusions were among the
      parameters that increased the prevalence of PI. Alternatively, prolene sutures,
      double-layered gloves, and the use of rifampicin Sv (RIS) decreased the incidence
      of PI. Although the presence of systemic diseases, unnoticed glove perforations,
      and perioperative blood transfusions increased PIs, prolene suture material,
      double-layered gloves, and the use of RIS decreased PIs.

PMID- 26200619
TI  - CONSORT: Different End-Points of Preoperative Nutrition and Outcome of Bowel
      Resection of Crohn Disease: A Randomized Clinical Trial.
AB  - Nutritional therapy cannot only improve nutritional status but also reduce bowel
      inflammation in Crohn disease (CD). The benefits of preoperative nutritional
      therapy on outcomes of surgery for CD have been demonstrated. However, the ideal
      end-points of preoperative nutrition in CD remain elusive. We conducted this
      study to figure out whether improvement of malnutrition or reduction of
      inflammation is the better end-point of preoperative nutrition for CD. This was a
      prospective, randomized study. All patients enrolled received preoperative
      nutrition with different end-points (improvement of malnutrition, IOM, or
      reduction of inflammation, ROI). The end-points were defined using serum albumin
      and body weight gain, and serum C-reactive protein (CRP), respectively.
      Postoperative complications, rate of fecal diversion, and postoperative
      recurrence of the disease were compared. A total of 108 patients were randomized
      and 91 patients (44 in IOM group and 47 in ROI group) completed this study. It
      took 25.57 +/- 11.68 days to achieve ROI and 45.29 +/- 18.47 days for IOM (P =
      0.0023). After nutritional therapy, serum CRP, CDAI, and serum albumin in both
      groups improved significantly. But patients in the IOM group had a higher albumin
      level and body weight gain compared with ROI group (P = 0.0026, P < 0.0001). When
      comparing postoperative complications, rate of fecal diversion, and postoperative
      recurrence, no significant differences were noted. Compared with IOM, ROI as the
      end-point of preoperative nutrition had the same benefits on operative outcomes
      in CD patients undergoing resection, but could be achieved in a shorter time
      (NCT01540942).

PMID- 26200621
TI  - Pediatric Online Evidence-Based Medicine Assignment Is a Novel Effective
      Enjoyable Undergraduate Medical Teaching Tool: A SQUIRE Compliant Study.
AB  - Evidence-based medicine (EBM) is delivered through a didactic, blended learning,
      and mixed models. Students are supposed to construct an answerable question in
      PICO (patient, intervention, comparison, and outcome) framework, acquire evidence
      through search of literature, appraise evidence, apply it to the clinical case
      scenario, and assess the evidence in relation to clinical context. Yet these
      teaching models have limitations especially those related to group work, for
      example, handling uncooperative students, students who fail to contribute,
      students who domineer, students who have personal conflict, their impact upon
      progress of their groups, and inconsistent individual acquisition of required
      skills. At Pediatrics Department, Faculty of Medicine, Cairo University, we
      designed a novel undergraduate pediatric EBM assignment online system to overcome
      shortcomings of previous didactic method and aimed to assess its effectiveness by
      prospective follow-up during academic years 2012 to 2013 and 2013 to 2014. The
      novel web-based online interactive system was tailored to provide sequential
      single and group assignments for each student. Single assignment addressed a
      specific case scenario question, while group assignment was teamwork that
      addressed different questions of same case scenario. Assignment comprised scholar
      content and skills. We objectively analyzed students' performance by criterion
      based assessment and subjectively by anonymous student questionnaire. A total of
      2879 were enrolled in 5th year Pediatrics Course consecutively, of them 2779
      (96.5%) logged in and 2554 (88.7%) submitted their work. They were randomly
      assigned to 292 groups. A total of 2277 (89.15%) achieved >= 80% of total mark
      (4/5), of them 717 (28.1%) achieved a full mark. A total of 2178 (85.27%) and
      2359 (92.36%) made evidence-based conclusions and recommendations in single and
      group assignment, respectively (P < 0.001). A total of 1102 (43.1%) answered
      student questionnaire, of them 898 (81.48%) found e-educational experience
      satisfactory, 175 (15.88%) disagreed, and 29 (2.6%) could not decide. A total of
      964 (87.47%) found single assignment educational, 913 (82.84%) found group
      assignment educational, and 794 (72.3%) enjoyed it. Web-based online interactive
      undergraduate EBM assignment was found effective in teaching medical students and
      assured individual student acquisition of concepts and skills of pediatric EMB.
      It was effective in mass education, data collection, and storage essential for
      system and student assessment.

PMID- 26200622
TI  - Coexistence of Anti-Glomerular Basement Membrane Antibodies and Anti-Neutrophil
      Cytoplasmic Antibodies in a Child With Human Leukocyte Antigen Susceptibility and
      Detailed Antibody Description: A Case Report.
AB  - Anti-glomerular basement membrane (anti-GBM) disease and anti-neutrophil
      cytoplasmic antibody (ANCA)-associated vasculitis both could cause rapidly
      progressive glomerulonephritis. The coexistence of ANCAs and anti-GBM antibodies
      was known as "double positive," which was extremely rare in children. We report a
      pediatric case with coexistence of ANCAs and anti-GBM antibodies. A 6-year-old
      girl presented with acute renal failure, hematuria, proteinuria, and oliguria.
      She was double positive of ANCAs specific to myeloperoxidase, and anti-GBM
      antibodies. Kidney biopsy confirmed linear immunoglobulin (Ig)G deposit along GBM
      and 100% of crescent formation in glomeruli; among them 83.3% were cellular
      crescents. Human leukocyte antigen (HLA) gene typing showed DRB1*1501, an allele
      strongly associated with anti-GBM disease, and DRB1*0405, an independent risk
      factor for renal failure in patients with ANCA-associated vasculitis. The titer
      of anti-GBM antibodies was 1:800, and the predominant IgG subclass was IgG1,
      which was closely related with severe kidney injury and worse outcome. The target
      antigen of anti-GBM antibodies was restricted on the noncollagen domain 1 of the
      alpha3 chain of type IV collagen (alpha3[IV]NC1), with recognitions to both
      epitopes, EA (alpha317-31) and EB (alpha3127-141). This is the first reported
      pediatric case with coexistence of ANCAs and anti-GBM antibodies, in which the
      HLA typing and immunologic characters of autoantibodies were identified. The
      findings on this early-onset patient are meaningful for understanding the
      mechanisms of both anti-GBM disease and ANCA-associated vasculitis.

PMID- 26200623
TI  - Factors Related to Relapse After 6 Months of Smoking Cessation Among Men in the
      Republic of Korea: A Cross-Sectional Study.
AB  - We identified factors associated with relapse after 6 months of smoking cessation
      (late relapse) among males of the Republic of Korea. Of the 222,707 smokers who
      visited public health center-based smoking cessation clinics (SCCs) between
      January 1, 2009 and mid-December 2009, we included 1720 individuals who
      successfully completed a 6-month smoking cessation program at an SCC. These
      participants were selected via a random stratified sampling design and completed
      an SCC user satisfaction survey between December 31, 2009 and January 6, 2010.
      Multiple logistic regression was used to identify factors associated with late
      relapse, and path analysis was employed to explore relationships among these
      factors. The frequency of late relapse was 21.6% (n = 372). Residence in a
      metropolitan area, low socioeconomic status, and the use of nicotine replacement
      therapy (NRT) were associated with statistically significant increases in late
      relapse, whereas greater access to counseling and more satisfaction with the SCC
      were associated with reduced late relapse. The path analysis showed that a
      greater number of cigarettes smoked daily and a younger age at smoking initiation
      exerted significant indirect effects on late relapse when NRT was employed.
      Residence in a metropolitan area indirectly prevented late relapse as counseling
      frequency increased. NRT use, counseling frequency, and SCC user satisfaction
      were affected by both smoking behavior and socioeconomic status. Relapse
      prevention efforts should concentrate on increasing both counseling frequency and
      SCC user satisfaction. Future studies should focus on the effect of NRT on the
      maintenance of long-term cessation at the population level in real-world
      settings.

PMID- 26200624
TI  - Assessment of the Relationship Between Red Cell Distribution Width and Multiple
      Sclerosis.
AB  - Accumulating data have shown that immune and inflammatory factors are involved in
      the pathogenesis of multiple sclerosis (MS), and loss of polyunsaturated fatty
      acids from plasma and blood cell membranes has also been reported in patients
      with MS, contributing to the variation of erythrocyte deformability. Therefore,
      the aim of this investigation was to assess the association between red blood
      cell distribution width (RDW) and MS. A total of 109 patients with MS and 130
      healthy individuals were enrolled into the study, and MS patients receiving
      treatment of subcutaneous recombinant Rebif (IFN-beta1a) were followed
      retrospectively. Complete blood cell counts and Expanded Disability Status Scale
      (EDSS) score were evaluated in patients with MS before and after treatment. RDW
      values were significantly higher in patients with MS compared with the controls
      (13.6 +/- 0.89 vs 12.8 +/- 0.38, P < 0.001); a positive correlation between RDW
      and EDSS score was observed in patients with MS (r = 0.789, P < 0.001).
      Significant differences in the value of RDW and EDSS score were observed between
      treatment-naive patients and treated patients (13.6 +/- 0.95 vs 12.7 +/- 0.44, P
      < 0.001; 3.6 +/- 1.39 vs 1.5 +/- 0.60, P < 0.001). RDW was associated
      independently with MS in logistic regression analysis (odds ratio = 7.007; 95%
      confidence interval [CI] 3.461-14.187; P < 0.001), and receiver-operating
      characteristics (ROC) analysis showed that a RDW measurement >13.11% evaluated MS
      with a sensitivity of 70.0% and a specificity of 84.7%, and the area under the
      ROC curve for RDW was calculated as 0.80 (95% CI 0.739-0.859, P < 0.001). The
      level of RDW was decreased in treatment responders with the reduction of EDSS
      score; a strong relationship was also observed in treatment responders between
      RDW and EDSS score (r = 0.733, P < 0.001), and covariance analysis indicated RDW
      values decreased significantly in treatment responders (P = 0.025). Our results
      suggest that elevated RDW values are associated with EDSS score in patients with
      MS, and the relationship is remarkably influenced by Rebif treatment; RDW may be
      a useful marker to estimate disability status and treatment effectiveness in
      patients with MS.

PMID- 26200625
TI  - Cardiovascular Events in Systemic Lupus Erythematosus: A Nationwide Study in
      Spain From the RELESSER Registry.
AB  - This article estimates the frequency of cardiovascular (CV) events that occurred
      after diagnosis in a large Spanish cohort of patients with systemic lupus
      erythematosus (SLE) and investigates the main risk factors for atherosclerosis.
      RELESSER is a nationwide multicenter, hospital-based registry of SLE patients.
      This is a cross-sectional study. Demographic and clinical variables, the presence
      of traditional risk factors, and CV events were collected. A CV event was defined
      as a myocardial infarction, angina, stroke, and/or peripheral artery disease.
      Multiple logistic regression analysis was performed to investigate the possible
      risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were
      enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269
      (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median
      [interquartile range] age 54.9 years [43.2-66.1], and SLE duration of 212.0
      months [120.8-289.0]). Strokes (5.7%) were the most frequent CV event, followed
      by ischemic heart disease (3.8%) and peripheral artery disease (2.2%).
      Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03
      [1.02-1.04]), hypertension (1.71 [1.20-2.44]), smoking (1.48 [1.06-2.07]),
      diabetes (2.2 [1.32-3.74]), dyslipidemia (2.18 [1.54-3.09]), neurolupus (2.42
      [1.56-3.75]), valvulopathy (2.44 [1.34-4.26]), serositis (1.54 [1.09-2.18]),
      antiphospholipid antibodies (1.57 [1.13-2.17]), low complement (1.81 [1.12
      2.93]), and azathioprine (1.47 [1.04-2.07]) as risk factors for CV events. We
      have confirmed that SLE patients suffer a high prevalence of premature CV
      disease. Both traditional and nontraditional risk factors contribute to this
      higher prevalence. Although it needs to be verified with future studies, our
      study also shows-for the first time-an association between diabetes and CV events
      in SLE patients.

PMID- 26200626
TI  - Biomechanical Comparison of Shorts With Different Pads: An Insight into the
      Perineum Protection Issue.
AB  - An intensive use of the bicycle may increase the risk of erectile dysfunction and
      the compression of the perineal area has been showed to be a major mechanism
      leading to sexual alterations compromising the quality of life. Manufacturers
      claim that pads contribute to increase cyclists perineal protection ensuring a
      high level of comfort. To investigate the influence of various cycling pads with
      regard to perineal protection and level of comfort. Nine club road cyclists rode
      20 min on a drum simulator, located at the Nutrition and Exercise Physiology
      Laboratory, at a constant speed and gear ratio wearing the shorts with 3 cycling
      pads of different design and thickness: basic (BAS), intermediate (INT), and
      endurance (END). Kinematics and pressure data were recorded at min 5, 15, and 20
      of the test using a motion capture system and a pressure sensor mat. The
      variables of interest were: 3-dimensional pelvis excursions, peak pressure, mean
      pressure, and vertical force. The comfort level was assessed with a ranking order
      based on the subjects' perception after the 20-min trials and measuring the
      vertical ground reaction force under the anterior wheel as well as the length of
      the center of pressure (COP) trajectory on the saddle. Results showed that the
      vertical force and the average value of mean pressure on the saddle significantly
      decreased during the 20-min period of testing for BAS and END. Mean peak pressure
      on the corresponding perineal cyclist area significantly increased only for BAS
      during the 20-min period. Interestingly objective comfort indexes measured did
      not match cyclists subjective comfort evaluation. The lower capacity of BAS to
      reduce the peak pressure on the corresponding perineal area after 20 min of
      testing, together with its positive comfort evaluation, suggest that a balance
      between protection and perceived comfort should be taken into account in the
      choice of the pad. Hence, the quantitative approach of objective comfort indexes
      introduced in this study could be helpful for manufacturers in the development of
      their protective pads.

PMID- 26200627
TI  - Increased Risk of Dementia in Patients With Acute Organophosphate and Carbamate
      Poisoning: A Nationwide Population-Based Cohort Study.
AB  - Organophosphate (OP) and carbamate (CM) are the most commonly used pesticides
      against insects. Little is known regarding the relationship between dementia and
      acute OP and CM poisoning. A nationwide population-based cohort study was
      conducted from the National Health Insurance Research Database in Taiwan. The
      incidence and relative risk of dementia were assessed in patients hospitalized
      for acute OP and CM poisoning from 2000 to 2011. The comparison cohort was
      matched with the poisoned cohort at a 4:1 ratio based on age, sex, and the year
      of hospitalization. During the follow-up period, the incidence of dementia was
      29.4 per 10,000 person-years in the poisoned group, and represented a 1.98-fold
      increased risk of dementia compared with the control cohort (95% confidence
      interval, 1.59-2.47). This study provides evidence on the association between
      dementia and acute OP and CM poisoning. Regular follow-up of poisoned patients
      for dementia is suggested.

PMID- 26200628
TI  - Minor-but-Complex Liver Resection: An Alternative to Major Resections for
      Colorectal Liver Metastases Involving the Hepato-Caval Confluence.
AB  - Major hepatectomy (MH) is often considered the only possible approach for
      colorectal liver metastasis (CRLM) at the hepato-caval confluence (CC), but it is
      associated with high morbidity and mortality. With the aim to reduce MH, we
      developed the "minor-but-complex" (MbC) technique, which consists in the
      resection of less than 3 adjacent liver segments with exposure of the CC and
      preservation of hepatic outflow until spontaneous maturation of peripheral
      intrahepatic shunts between main hepatic veins. We have evaluated applicability
      and outcome of MbC resections for the treatment of CRLM involving the CC. In this
      retrospective cohort study, all consecutive liver resections (LR) performed for
      CRLM located in segments 1, 7, 8, or 4a were classified as MINOR - removal of <3
      adjacent segments; MbC - removal of <3 adjacent segments with CC exposure; and MH
      - removal of >= 3 adjacent segments. The rate of avoided MH was obtained by the
      difference between the rate of potentially MH (PMH) plus potentially inoperable
      cases and the rate of the MH performed. Taking into account that postoperative
      mortality is mainly related to the amount of resected liver, MbC was compared
      with minor resections for safety, complexity, and outcome. Of the 59 LR analyzed,
      29 (49.1%) were deemed PMH and 4 (6.8%) potentially inoperable. Eventually, MH
      was performed only in 8 (13.5%) with a decrease rate of 42.4%. Minor LR was
      performed in 23 (39.0%) and MbC LR in 28 (47.5%) patients. Among MbC cases, 32.1%
      had previous liver treatments, 39.3% required vascular reconstruction (no
      reconstructed vessel thrombosis occurred before maturation of peripheral
      intrahepatic shunts between main hepatic veins), and 7.1% had grade IIIb-IV
      complications, their median hospital stay was 9 days and 90-day mortality was 0%.
      After a median follow-up of 22.2 months, oncological results were comparable with
      those of minor resections. MbC hepatectomy lowers the need for MH and allows for
      the resection of potentially inoperable patients without negative impact on
      safety and survival.

PMID- 26200629
TI  - Atypical Hepatocellular Neoplasm With Peliosis in Cirrhotic Liver Versus
      Hepatocellular Carcinoma: A Diagnostic Trap.
AB  - Atypical hepatocellular neoplasm (AHN) is an adenoma-like hepatic tumor that even
      occurs in noncirrhotic liver of males (any age) or females >= 50 years old, or
      associates focal atypical features. In this article, 2 unusual cases diagnosed in
      elderly cirrhotic patients, unrelated to steroids, are presented. The first case
      was incidentally diagnosed in an 83-year-old female. During laparoscopic surgery
      for cholecystectomy, hemoperitoneum was installed and laparotomy was necessary to
      remove a 70-mm nodular encapsulated hepatic tumor that was microscopically
      composed by hepatocyte-like cells with clear cytoplasm, arranged in 1- to 2-cell
      thick plates and intermingled with areas of peliosis, negative for alpha
      fetoprotein (alphaFP), p53, and keratin 7, with low Ki67 index and intact
      reticulin framework. The second case was incidentally diagnosed at ultrasound
      examination in a 66-year-old male. The surgical specimen was a 50-mm solid
      multinodular tumor that microscopically consisted of 3-cell-thick plates of
      hepatocyte-like cells with acinar, pseudoglandular, and trabecular architecture,
      intermingled with peliotic areas, without nuclear atypia and disintegrated
      reticulin framework. Both of the cases occurred in cirrhotic liver. The tumor
      cells were marked by AE1/AE3 keratin, displayed a Ki67 index < 5% and were
      negative for alphaFP, p53, and keratin 7. No recurrences or any other disorder
      occurred 6 months after surgery. In cirrhotic liver, adenomas with peliosis that
      do not satisfy all the diagnosis criteria synthesized in the article should be
      considered AHNs and differential diagnosis includes hepatocellular carcinoma but
      also focal nodular hyperplasia, regenerative nodules, and dysplastic nodules.
      This histological entity is not yet included in the WHO Classification list.

PMID- 26200630
TI  - Safety of Exposure From Extremely Low Frequency Magnetic Fields During Prenatal
      Ultrasound Examinations in Clinicians and Pregnant Women.
AB  - Investigations into the safety of ultrasonography in pregnancy have focused on
      the potential harm of ultrasound itself. However, no data have been published
      regarding the electromagnetic fields that ultrasound devices might produce. This
      study is the first to measure extremely low-frequency magnetic field (ELF-MF)
      exposure of clinicians and pregnant women during prenatal ultrasound examinations
      in the examination room from 2 different ultrasound devices and compare them with
      ELF-MFs during patient consultation in the consulting room.The ELF-MF intensities
      that clinicians and pregnant women were exposed to were measured every 10 seconds
      for 40 prenatal ultrasound examinations using Philips iU22 or Accuvix V20
      Prestige machines and 20 patient consultations in a consulting room using
      portable ELF-MF measurement devices. The mean ELF-MF exposure of both clinicians
      and pregnant women was 0.18 +/- 0.06 mG during prenatal ultrasound examination.
      During patient consultation, the mean ELF-MF exposures of clinicians and pregnant
      women were 0.10 +/- 0.01 and 0.11 +/- 0.01 mG, respectively. Mean ELF-MF
      exposures during prenatal ultrasound examination were significantly higher than
      those during patient consultations (P < 0.001 by Mann-Whitney U test).Our results
      provide basic reference data on the ELF-MF exposure of both clinicians and
      pregnant women during prenatal ultrasound monitoring from 2 different ultrasound
      devices and patient consultation, all of which were below 2 mG, the most
      stringent level considered safe in many studies, thus relieving any anxiety of
      clinicians and pregnant women regarding potential risks of ELF-MFs.

PMID- 26200631
TI  - Acetaminophen Poisoning and Risk of Acute Pancreatitis: A Population-Based Cohort
      Study.
AB  - The aim of this study was to assess whether acetaminophen poisoning is associated
      with a higher risk of acute pancreatitis. We conducted a retrospective cohort
      study by using the longitudinal population-based database of Taiwan's National
      Health Insurance (NHI) program between 2000 and 2011. The acetaminophen cohort
      comprised patients aged >= 20 years with newly identified acetaminophen poisoning
      (N = 2958). The comparison cohort comprised randomly selected patients with no
      history of acetaminophen poisoning. The acetaminophen and comparison cohorts were
      frequency matched by age, sex, and index year (N = 11,832) at a 1:4 ratio. Each
      patient was followed up from the index date until the date an acute pancreatitis
      diagnosis was made, withdrawal from the NHI program, or December 31, 2011. Cox
      proportional hazard regression models were used to determine the effects of
      acetaminophen on the risk of acute pancreatitis.The risk of acute pancreatitis
      was 3.11-fold higher in the acetaminophen cohort than in the comparison cohort
      (11.2 vs 3.61 per 10,000 person-years), with an adjusted hazard ratio of 2.40
      (95% confidence interval, 1.29-4.47). The incidence rate was considerably high in
      patients who were aged 35 to 49 years, men, those who had comorbidities, and
      within the first year of follow-up.Acetaminophen poisoning is associated with an
      increased risk of acute pancreatitis. Additional prospective studies are
      necessary to verify how acetaminophen poisoning affects the risk of acute
      pancreatitis.

PMID- 26200632
TI  - Sinonasal Angiomatous Polyp: Evaluation With 2-Phase Helical Computed Tomography.
AB  - Sinonasal angiomatous polyp (SAP) is a rare benign nontumorous lesion and
      previously considered lack of characteristic computed tomography (CT) findings.
      This study aimed to evaluate 2-phase helical CT for characterization of SAP.
      Twelve patients with pathologically confirmed SAP underwent 2-phase helical CT
      preoperatively. After injection of 80 mL contrast material at a rate of 3 mL/s,
      early and delayed phases were obtained with delays of 30 and 120 s, respectively.
      The degree and pattern of enhancement were visually analyzed. The attenuation
      changes were also analyzed quantitatively by measuring CT values and compared
      with those of the internal maxillary artery (IMA). All 12 cases showed vessel
      like marked heterogeneous enhancement at both early and delayed phases. An
      irregular linear, nodular, and patchy enhancement pattern was found at the early
      phase, and enlarged and fused together, that is, progressive enhancement pattern
      was found at the delayed phase. There was no significant difference between the
      CT values of SAP and those of the IMA at the plain, arterial phase, and delayed
      phase (53 +/- 6 Hounsfield units [HU] vs 56 +/- 7 HU, 187 +/- 56 HU vs 209 +/- 71
      HU, and 143 +/- 22 HU vs 139 +/- 19 HU, respectively, P = 0.361, 0.429, and
      0.613, respectively). Vessel-like marked heterogeneous enhancement was a
      characteristic CT feature of SAP, and progressive enhancement on 2-phase helical
      CT could further convince the diagnosis.

PMID- 26200633
TI  - Radiographic Parameters in Adult Degenerative Scoliosis and Different Parameters
      Between Sagittal Balanced and Imbalanced ADS Patients.
AB  - A retrospective study. To summarize and describe the radiographic parameters of
      adult degenerative scoliosis (ADS) and explore the radiological parameters which
      are significantly different in sagittal balanced and imbalanced ADS patients. ADS
      is the most common type of adult spinal deformity. However, no comprehensive
      description of radiographic parameters in ADS patients has been made, and few
      studies have been performed to explore which radiological parameters are
      significantly different between sagittal balanced and imbalanced ADS patients.
      Medical records of ADS patients in our outpatient clinic from January 2012 to
      January 2014 were reviewed. Demographic data including age and sex, and
      radiographic data including the coronal Cobb angle, location of apical
      vertebra/disc, convexity of the curve, degree of apical vertebra rotation, curve
      segments, thoracic kyphosis (TK), lumbar lordosis (LL), thoracolumbar kyphosis
      (TL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), sagittal
      vertical axis (SVA), and PI minus LL (PI-LL) were reviewed to make comprehensive
      description of radiographic parameters of ADS. Furthermore, patients were divided
      into 2 groups according to whether the patients' sagittal plane was balanced:
      Group A (imbalanced, SVA > 5 cm) and Group B (balanced, SVA  <= 5 cm).
      Demographic and radiological parameters were compared between these 2 groups. A
      total of 99 patients were included in this study (Group A = 33 and Group B = 66;
      female = 83 and male = 16; sex ratio = 5:1). The median of age were 67 years
      (range: 41-92 years). The median of coronal Cobb angle and length of curve was 23
      (range: 10-75 degrees ) and 5 segments (range: 3-7), respectively. The most
      common location of apical vertebra was at L2 to L3 (81%) and the median of degree
      of apical vertebra rotation was 2 degrees  (range: 1-3). Our study also showed
      significant correlations between coronal Cobb angle and curve segments (r = 0.23,
      P < 0.005) and degree of apical vertebra rotation (r = 0.53, P < 0.005). With
      regard to the sagittal balance, there were significant differences in age, LL,
      PT, coronal Cobb angle, degree of apical vertebra rotation, and PI-LL between
      imbalanced group and balanced group (all P < 0.05); however, no significant
      difference was observed in gender, TK, TL, SS, and PI. Our study provided the
      general radiographic parameters of ADS. Weak or moderate but significant
      correlations between coronal Cobb angle and curve segments and degree of apical
      vertebra rotation were observed. Furthermore, age, coronal Cobb angle, LL, PT,
      and PI-LL were significantly different between sagittal balanced and imbalanced
      ADS patients.

PMID- 26200634
TI  - Effect of Preoperative Biliary Drainage on Complications Following
      Pancreatoduodenectomy: A Meta-Analysis.
AB  - Preoperative biliary drainage (PBD) prior to pancreatoduodenectomy (PD) is still
      controversial; therefore, the aim of this study was to examine the impact of PBD
      on complications following PD. A meta-analysis was carried out for all relevant
      randomized controlled trials (RCTs), prospective and retrospective studies
      published from inception to March 2015 that compared PBD and non-PBD (immediate
      surgery) for the development of postoperative complications in PD patients.
      Pooled odds ratio (OR) and 95% confidence interval (CI) were estimated using
      fixed-effect analyses, or random-effects analyses if there was statistically
      significant heterogeneity (P < 0.05). Eight RCTs, 13 prospective studies, 20
      retrospective studies, and 3 Chinese local retrospective studies with 6286
      patients were included in this study. In a pooled analysis, there were no
      significant differences between PBD and non-PBD group in the risks of mortality,
      morbidity, intra-abdominal abscess, sepsis, hemorrhage, pancreatic leakage, and
      biliary leakage. However, subgroup analysis of RCTs yielded a trend toward
      reduced risk of morbidity in PBD group (OR 0.48, CI 0.24 to 0.97; P = 0.04).
      Compared with non-PBD, PBD was associated with significant increase in the risk
      of infectious complication (OR 1.52, CI 1.07 to 2.17; P = 0.02), wound infection
      (OR 2.09, CI 1.39 to 3.13; P = 0.0004), and delayed gastric emptying (DGE) (OR
      1.37, CI 1.08 to 1.73; P = 0.009). This meta-analysis suggests that biliary
      drainage before PD increased postoperative infectious complication, wound
      infection, and DGE. In light of the results of the study, PBD probably should not
      be routinely carried out in PD patients.

PMID- 26200635
TI  - Idiopathic Pneumonia Syndrome and Thrombotic Microangiopathy Following
      Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation and
      Posttransplant Cyclophosphamide: A Case Report.
AB  - Posttransplant high-dose cyclophosphamide (pT-HDCy) following T-cell-replete
      haploidentical bone marrow (BM) transplantation has been successfully utilized to
      control alloreactivity, mainly in ameliorating graft-versus-host disease (GVHD)
      and graft rejection. Recently, peripheral blood stem cells (PBSCs) have also been
      suggested to be a feasible and effective graft alternative to BM in the same
      setting. We report a case with refractory Hodgkin lymphoma treated with
      haploidentical PBSC transplantation with nonmyeloablative conditioning and pT
      HDCy. Although engraftment with complete donor chimerism was achieved without
      classical GVHD, the patient suffered from idiopathic pneumonia syndrome followed
      by thrombotic microangiopathy. Although idiopathic pneumonia syndrome and
      thrombotic microangiopathy improved after treatment, the patient's lymphoma
      rapidly progressed nonetheless. This outcome may suggest that the alloreactivity
      against the classical GVHD targets is successfully eradicated by pT-HDCy, but
      alloreactivity against the lungs and endothelial cells is differentially
      preserved when utilizing granulocyte colony-stimulating factor-mobilized PBSCs as
      the graft source. The graft-versus-Hodgkin lymphoma effect was not observed in
      our patient.

PMID- 26200636
TI  - Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After
      Laparoscopic Total Mesorectal Excision: The Korean Laparoscopic Colorectal
      Surgery Study Group.
AB  - This study aims to validate the oncologic outcomes of anastomotic leakage (AL)
      after laparoscopic total mesorectal excision (TME) in a large multicenter cohort.
      The impact of AL after laparoscopic TME for rectal cancer surgery has not yet
      been clearly described. This was a multicenter retrospective study of 1083
      patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0
      III). AL was defined as an anastomotic complication within 30 days of surgery
      irrespective of requiring a reoperation or interventional radiology. Estimated
      local recurrence (LR), disease-free survival (DFS), and overall survival (OS)
      were compared between the leakage group and the no leakage group using the log
      rank method. Multivariate Cox-regression analysis was used to adjust confounding
      for survival. The incidence of AL was 6.4%. Mortality within 30 days of surgery
      occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no
      leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P =
      0.011). Five-year DFS and OS were significantly lower in the leakage group than
      the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P =
      0.007). Multivariate analysis showed that AL was an independent poor prognostic
      factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]:
      1.0-2.6; P = 0.042, HR = 2.1; 95% CI: 1.0-4.2; P = 0.028, respectively). AL after
      laparoscopic TME was significantly associated with an increased rate of LR,
      systemic recurrence and poor OS.

PMID- 26200638
TI  - Prevalence of and Predictors for Frequent Utilization of Emergency Department: A
      Population-Based Study.
AB  - Frequent emergency department (ED) users contribute to a disproportionate number
      of ED visits that consume a substantial amount of medical resources.
      Additionally, people with frequent ED visits may be at greater risks of illnesses
      and injury and are vulnerable to even more severe health events. We conducted,
      based on a nationally representative sample, a population-based study to estimate
      the prevalence of frequent ED users among all ED users, and to explore factors
      associated with frequent ED visits. This is a population-based cross-sectional
      study. Data of 1 million people randomly selected from all beneficiaries of
      Taiwan's National Health Insurance claim database in 2010 were analyzed to
      estimate the distribution of ED visit among ED users. Multivariate logistic
      regression was employed to calculate the independent associations of factors with
      prevalence of frequent (4-12 ED visits per year) and highly frequent (>12 ED
      visits per year) ED visits. Of the 1 million beneficiaries 170,475 subjects used
      ED service in 2010 and 103,111 (60.5%), 37,964 (22.3%), 14,881 (8.7%), 14,041
      (8.2%), and 460 (0.3%) subjects had 1, 2, 3, 4 to 12, and more than 12 ED visits,
      respectively. ED users with 4 to 12 visits and those with >12 visits
      disproportionally accounted for 24.1% and 3.0%, respectively, of all ED visits in
      2010. We noted significant associations of frequent ED visit with a number of
      factors including socio-demographics, health care utilization, and comorbidity.
      Among them, the most increased adjusted odds ratio (AOR) was noted for
      hospitalization during the past year (AOR = 1.85) and younger ages (1-6 years)
      (AOR = 1.84). On the contrary, the significant predictors for highly frequent ED
      visit with greater AOR included hospitalization during the past year (AOR =
      3.95), > 12 outpatient visits during the past year (AOR = 2.66), and a history of
      congestive heart failure (AOR = 2.64) and psychiatric disorders (AOR = 2.35).
      People admitted and with frequent outpatient visits were at greater risk of
      frequent ED visit. Because people with a history of various comorbidities were
      also vulnerable to become frequent ED users, careful management of those
      comorbidities by clinicians may help further reduce the likelihood of frequent ED
      visit.

PMID- 26200637
TI  - Increased Subsequent Risk of Peptic Ulcer Diseases in Patients With Bipolar
      Disorders.
AB  - Previous studies have reported that patients with bipolar disorders (BDs) exhibit
      increased physical comorbidity and psychological distress. Studies have shown
      that schizophrenia and anxiety increase the risk of peptic ulcer diseases (PUDs).
      Therefore, we conducted this study to determine the association between these 2
      diseases and examine the possible risk factors. We used patients diagnosed with
      BDs from the Taiwan National Health Insurance Research Database. A comparison
      cohort comprising patients without BDs was frequency matched by age, sex, and
      comorbidities, and the occurrence of PUDs was evaluated in both the cohorts. The
      BD and non-BD cohort consisted of 21,060 patients with BDs and 84,240 frequency
      matched patients without BDs, respectively. The incidence of PUDs (hazard ratio,
      1.51; 95% confidence interval, 1.43-1.59; P < 0.001) was higher among the
      patients with BDs than the control patients. Cox models showed that irrespective
      of comorbidities, BDs were an independent risk factor for PUDs. Patients with BDs
      exhibit a substantially higher risk for developing PUDs. According to our data,
      we suggest that, following a diagnosis of BD, practitioners could notice the
      occurrence of PUD and associated prevention. Further prospective clinical studies
      investigating the relationship between BDs and PUDs are warranted.

PMID- 26200639
TI  - Association Between Awareness of Hypertension and Health-Related Quality of Life
      in a Cross-Sectional Population-Based Study in Rural Area of Northwest China.
AB  - Hypertensive patients have more complex health care needs and are more likely to
      have poorer health-related quality of life than normotensive people. The
      awareness of hypertension could be related to reduce health-related quality of
      life. We propose the use of quantile regression to explore more detailed
      relationships between awareness of hypertension and health-related quality of
      life. In a cross-sectional, population-based study, 2737 participants (including
      1035 hypertensive patients and 1702 normotensive participants) completed the
      Short-Form Health Survey. A quantile regression model was employed to investigate
      the association of physical component summary scores and mental component summary
      scores with awareness of hypertension and to evaluate the associated factors.
      Patients who were aware of hypertension (N = 554) had lower scores than patients
      who were unaware of hypertension (N = 481). The median (IQR) of physical
      component summary scores: 48.20 (13.88) versus 53.27 (10.79), P < 0.01; the
      mental component summary scores: 50.68 (15.09) versus 51.70 (10.65), P = 0.03.
      adjusting for covariates, the quantile regression results suggest awareness of
      hypertension was associated with most physical component summary scores quantiles
      (P < 0.05 except 10th and 20th quantiles) in which the beta-estimates from -2.14
      (95% CI: -3.80 to -0.48) to -1.45 (95% CI: -2.42 to -0.47), as the same
      significant trend with some poorer mental component summary scores quantiles in
      which the beta-estimates from -3.47 (95% CI: -6.65 to -0.39) to -2.18 (95% CI: 
      4.30 to -0.06). The awareness of hypertension has a greater effect on those with
      intermediate physical component summary status: the beta-estimates were equal to 
      2.04 (95% CI: -3.51 to -0.57, P < 0.05) at the 40th and decreased further to 
      1.45 (95% CI: -2.42 to -0.47, P < 0.01) at the 90th quantile. Awareness of
      hypertension was negatively related to health-related quality of life in
      hypertensive patients in rural western China, which has a greater effect on
      mental component summary scores with the poorer status and on physical component
      summary scores with the intermediate status.

PMID- 26200640
TI  - Subcutaneous Versus Submuscular Anterior Transposition of the Ulnar Nerve for
      Cubital Tunnel Syndrome: A Systematic Review and Meta-Analysis of Randomized
      Controlled Trials and Observational Studies.
AB  - Subcutaneous and submuscular anterior ulnar nerve transposition have been widely
      used in patients with cubital tunnel syndrome. However, the reliable evidence in
      favor of 1 of 2 surgical options on clinical improvement remains controversial.
      To maximize the value of the available literature, we performed a systematic
      review and meta-analysis to compare subcutaneous versus submuscular anterior
      ulnar nerve transposition in patients with ulnar neuropathy at the elbow. PubMed,
      Cochrane Library, and EMBASE databases were searched for randomized and
      observational studies that compared subcutaneous transposition with submuscular
      transposition of ulnar nerve for cubital tunnel syndrome. The primary outcome was
      clinically relevant improvement in function compared to the baseline. Randomized
      and observational studies were separately analyzed with relative risks (RRs) and
      95% confidence intervals (CIs). Two randomized controlled trials (RCTs) and 7
      observational studies, involving 605 patients, were included. Our meta-analysis
      suggested that no significant differences in the primary outcomes were observed
      between comparison groups, both in RCT (RR, 1.16; 95% CI 0.68-1.98; P = 0.60; I2=
      81%) and observational studies (RR, 1.01; 95% CI 0.95-1.08; P = 0.69; I2 = 0%).
      These findings were also consistent with all subgroup analyses for observational
      studies. In the secondary outcomes, the incidence of adverse events was
      significantly lower in subcutaneous group than in submuscular group (RR, 0.54;
      95% CI 0.33-0.87; P = 0.01; I2 = 0%), whereas subcutaneous transposition failed
      to reveal more superiority than submuscular transposition in static two-point
      discrimination (MD, 0.04; 95% CI -0.18-0.25; P = 0.74; I = 0%). The available
      evidence is not adequately powered to identify the best anterior ulnar nerve
      transposition technique for cubital tunnel syndrome on the basis of clinical
      outcomes, that is, suggests that subcutaneous and submuscular anterior
      transposition might be equally effective in terms of postoperative clinical
      improvement. However, differences in clinical outcomes metrics should be noted,
      and these findings largely rely on the outcomes data from observational studies
      that are potentially subject to a high risk of selection bias. Therefore, more
      high-quality and adequately powered RCTs with standardized clinical outcomes
      metrics are necessary for proper comparison of these techniques.

PMID- 26200641
TI  - Self-Expandable Metallic Stent Placement in Malignant Gastric Outlet Obstruction:
      A Comparison Between 2 Brands of Stents.
AB  - Malignant gastric outlet obstruction is a late complication of intraabdominal
      malignancy. Self-expandable metallic stent placement has been a safe palliative
      treatment to relieve obstructive symptoms. We aimed to assess the efficacy and
      safety of metallic stents in our patients and analyzed the clinical outcome of
      different brands. Seventy-one patients with inoperable gastric outlet obstruction
      receiving WallFlex enteral stents (WallFlex group) or Bonastents (Bonastent
      group) since April 2010 were analyzed retrospectively. The overall technical and
      clinical success rates of stent placement were 100% and 93%, respectively. The
      baseline characteristics and clinical outcomes including procedure-related
      complications, restenosis, and reintervention rates were comparable between the 2
      groups. However, the Bonastent group had a higher rate of stent fracture than the
      WallFlex group (13.3% vs 0%, P = 0.03). The mean duration of overall stent
      patency was 132.7 days. The mean duration of survival was 181.9 days. Resumption
      of regular diet or low residual diet at day 7 after stent insertion predicted
      stent patency (hazard ratio [HR]: 0.28, P = 0.01). Cancer with gastric origin
      (HR: 0.25, P = 0.045) and poststent chemotherapy (HR: 0.38, P = 0.006) predicted
      lower mortality; however, peritoneal carcinomatosis (HR: 3.09, P = 0.04)
      correlated with higher mortality. Metallic stent placement is a safe and
      effective method for relieving gastric outlet obstruction. Except higher rate of
      stent fracture in the Bonastent group, there is no significant difference in
      clinical outcomes between the Bonastent group and the WallFlex group.

PMID- 26200642
TI  - Ultrasonography-Guided Core Biopsy of Supraclavicular Lymph Nodes for Diagnosis
      of Metastasis and Identification of Epidermal Growth Factor Receptor (EGFR)
      Mutation in Advanced Lung Cancer.
AB  - The aim of this study was to evaluate the diagnostic performance of
      ultrasonography (US)-guided core biopsy of a supraclavicular lymph node (SCN) for
      detecting metastasis and epidermal growth factor receptor (EGFR) mutations. We
      included 229 patients who underwent US-guided core biopsy of SCN with lung cancer
      from January 2011 to December 2013. We evaluated the morphologic characteristics
      and measured the sizes of SCNs on US and chest computed tomography (CT). The
      clinical stage, maximum standardized uptake value (SUV max) on 18F
      fluorodeoxyglucose positron emission tomography, and the morphology on US and CT
      in the positive metastasis were compared with those in the negative metastasis.
      The prevalence of EGFR mutations of the adenocarcinoma and procedure-related
      complication was investigated. The accuracy of US-guided core biopsy of SCN
      diagnosing metastasis was 97.8% (224/229). The cutoff values (sensitivity;
      specificity; area under the receiver operating characteristic curve, 95%
      confidence interval [CI]) of the short-axis dimension of SCN on CT were 0.85 cm
      (72.3%; 80.6%; 0.808, 95% CI: 0.740-0.875), on US 0.75 cm (73.5%; 84.8%; 0.843,
      95% CI: 0.788-0.897), and that of SUV max 4.05 (79.1%; 81.8%; 0.853, 95% CI:
      0.780-0.925). The mutations were positive in 35.8% with adenocarcinoma. There
      were no procedure-related complications of US-guided SCN core biopsy. US-guided
      SCN core biopsy is a reliable and safe method for detecting metastasis,
      histologic subtyping, and identifying the EGFR mutation in the advanced lung
      cancers. It may be a substitute for more invasive lung biopsy as an initial
      tissue confirmation in the advanced disease.

PMID- 26200643
TI  - Primary Pulmonary Diffuse Large B-Cell Lymphoma on FDG PET/CT-MRI and DWI.
AB  - Primary pulmonary diffuse large B-cell lymphoma (PPDLBCL) directly arising from
      lung tissue is extremely rare. It may usually be misdiagnosed as inflammation
      including pulmonary tuberculosis, even lung cancer, because its clinical symptoms
      and signs are often nonspecific. The final diagnosis usually depends on lung
      biopsy. Herein, we report a case of PPDLBCL and review of diagnosis of this
      disease, particularly in radiology. A 44-year-old man presented with cough,
      sputum, and intermittent chest pain for 4 weeks. Multiple radiological
      examinations showed an irregular mass in the right upper lobe with ground-glass
      opacities around it and air-filled bronchi in the consolidation.
      Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      magnetic resonance imaging (MRI) detected positive FDG uptake, and diffusion
      weighted imaging indicated abnormal hyperintension in the lesion. Inflammation
      was suspected, but malignance cannot be excluded. Finally, ultrasound-guided fine
      needle aspiration cytology was performed for histological examination and
      definitive diagnosis yielded lymphomatous cells infiltration in the right upper
      lobe. This report emphasizes the significance of multimodality radiological
      examinations. Multimodality imaging contributes to proper diagnosis, staging, and
      management of lymphomas.

PMID- 26200644
TI  - Increased Risk of Chronic Fatigue Syndrome Following Atopy: A Population-Based
      Study.
AB  - Several hypotheses have been proposed to explain the etiopathogenesis of chronic
      fatigue syndrome (CFS), including immune dysregulation. However, few population
      based prospective cohort studies have been conducted on CFS and atopy. We
      investigated the relationship between atopy and CFS by using a population-based
      cohort study. In this prospective, population-based cohort study of the National
      Health Insurance Research Database, we identified 42,558 patients with atopy and
      170,232 patients without atopy from 2005 to 2007 with follow-up to 2011. The
      incidence rates and risks for CFS were estimated using Cox proportion hazards
      regression. The overall incidence rate of CFS was higher in the atopy cohort
      compared with the nonatopy cohort (1.37 versus 0.87 per 1000 person-year), with
      an adjusted hazard ratio of 1.48 (95% confidence interval 1.30-1.69). The risk of
      CFS in the atopy cohort increased 1.47- to 1.50-fold for each nonexisting
      comorbidity. Patients with numerous atopic symptoms exhibited a biological
      gradient of increasing risk for CFS, and the risk changed significantly after
      adjustment for age, sex, and comorbidities, increasing from 1.46- to 2.59-fold.
      We revealed that atopy is associated with CFS, particularly in patients with
      numerous atopic syndromes. The actual mechanism for CFS development in patients
      with atopy remains unclear and requires further investigation. We recommend
      researching the subsequent fatigue symptom in patients with atopy, particularly
      those with multiple atopic syndromes.

PMID- 26200645
TI  - A Retrospective Study of the Impact of Intraoperative Intact Parathyroid Hormone
      Monitoring During Total Parathyroidectomy for Secondary Hyperparathyroidism:
      STARD Study.
AB  - The study aimed to evaluate the diagnostic accuracy of intraoperative intact
      parathyroid hormone (IO-iPTH) in patients with secondary hyperparathyroidism
      (HPT). The cut-off for IO-iPTH monitoring remains unknown. This was a single
      center retrospective review of 226 consecutive patients (107 males and 119
      females) who underwent parathyroidectomy for secondary HPT between May 2010 and
      March 2014. The predetermined cut-off for IO-iPTH was a 70% IO-iPTH drop from
      baseline 10 minutes after total parathyroidectomy and thymectomy. We used <60
      pg/mL iPTH value on postoperative day 1 (POD1) as an indicator of successful
      removal of parathyroid glands and reviewed the frequency of reoperation other
      than in autografted sites during the observation period. This study was based on
      the Standards for the Reporting of Diagnostic accuracy compliant. The reoperation
      rate in patients with >60 pg/mL iPTH value (POD1) was significantly higher than
      that in patients with <60 pg/mL iPTH value (POD1), (13.0% versus 0.5% P = 0.003).
      Sensitivity, specificity, and accuracy of >70% IO-iPTH drop were 97.5%, 52.2%,
      and 92.9%, respectively, this criterion was demonstrated to be beneficial in 26
      patients. In 5 patients, <70% IO-iPTH drop was observed and further exploration
      enabled sufficient removal of parathyroid glands. In 21 patients, although fewer
      than 4 parathyroid glands were removed after enough explorations, >70% IO-iPTH
      drop enabled termination of operations and iPTH value (POD1) was <60 pg/mL.An
      iPTH value of <60 pg/mL (POD1) was a good predictor for successful
      parathyroidectomy. A 70% IO-iPTH drop from the baseline was appropriate to
      determine sufficient parathyroid gland removal during parathyroidectomy for
      patients with secondary HPT. [Corrected]

PMID- 26200646
TI  - Timeliness of Diagnosing Lung Cancer: Number of Procedures and Time Needed to
      Establish Diagnosis: Being Right the First Time.
AB  - To study number of procedures and time to diagnose lung cancer and factors
      affecting the timeliness of clinching this diagnosis. Retrospective cohort study
      of lung cancer patients who consecutively underwent diagnostic bronchoscopy in 1
      year (October 2013 to September 2014). Out of 101 patients diagnosed with lung
      cancer from bronchoscopy, average time interval between first abnormal computed
      tomogram (CT) scan-to-1st procedure, 1st procedure-to-diagnosis, and 1st abnormal
      CT scan-to-diagnosis was 16 +/- 26, 11 +/- 19, and 27 +/- 33 days, respectively.
      These intervals were significantly longer in those requiring repeat procedures.
      Multivariate analysis revealed inconclusive 1st procedure to be the predictor of
      prolonged (>30 days) CT scan to diagnosis time (P = 0.04). Twenty-nine patients
      (28.7%) required repeat procedures (n = 63). Reasons behind repeating the
      procedures were inadequate procedure (n = 14), inaccessibility of lesion (n = 9),
      inappropriate procedure (n = 5), mutation analysis (n = 2), and others (n = 2).
      Fifty had visible endo-bronchial lesion, 20 had positive bronchus sign, and 83
      had enlarged mediastinal/hilar lymph-nodes or central masses adjacent to the
      airways. Fewer procedures, and shorter procedure to diagnosis time, were observed
      in those undergoing convex probe endobronchial ultrasound-transbronchial needle
      aspiration (EBUS-TBNA) (P = 0.04). Most patients exhibit enlarged mediastinal
      lymph node or mass adjacent to the central airway accessible by convex probe EBUS
      TBNA. Hence, combining it with conventional bronchoscopic techniques such as
      bronchoalveolar lavage, brush, and forceps biopsy increases detection rate, and
      reduces number of procedures and time to establish diagnosis. This may translate
      into cost and resource savings, timeliness of diagnosis, greater patient
      satisfaction, and conceivably better outcomes.

PMID- 26200647
TI  - Hepatocellular Carcinoma Patients With Performance Status 1 Deserve New
      Classification and Treatment Algorithm in the BCLC System.
AB  - Hepatocellular carcinoma (HCC) patients with performance status (PS) 1 or 2 are
      considered similar in the Barcelona Clinic Liver Cancer (BCLC) system. The
      rationales are not fully studied. A total of 693 and 335 HCC patients were
      classified as PS 1 and 2, respectively, in a prospectively followed up database.
      One-to-one matched pairs between HCC patients were generated by using the
      propensity score with matching model. Survival analysis was performed and the
      hazard ratio was calculated with the Cox proportional hazards model. Patients
      with PS 1 were significantly younger and had better liver and renal functions
      compared with patients with PS 2 (all P < 0.05). Patients with PS 1 had earlier
      BCLC stages and higher chances to undergo curative treatments (both P < 0.05).
      After matching, patients with PS 1 or 2 had similar age, gender, liver diseases,
      severity of cirrhosis, tumor burden, and treatments (all P > 0.05); patients with
      PS 1 had significantly better prognosis compared with patients with PS 2 (P <
      0.05). There were 68% of patients with PS 1 that underwent aggressive treatments
      (resection, transplantation, percutaneous ablation, or transarterial
      chemoembolization), which were significantly correlated to better outcome with a
      hazard ratio of 0.539 in the matching model (P = 0.002). For patients with PS 2,
      aggressive treatments were not significantly associated with better long-term
      survival. Aggressive treatments provide survival benefits for patients with PS 1,
      but not for patients with PS 2. HCC patients with PS 1 or 2 should be considered
      clinically different disease entities in the BCLC system.

PMID- 26200648
TI  - Immunonutrition Support for Patients Undergoing Surgery for Gastrointestinal
      Malignancy: Preoperative, Postoperative, or Perioperative? A Bayesian Network
      Meta-Analysis of Randomized Controlled Trials.
AB  - Enteral immunonutrition (EIN) has been established to be as a significantly
      important modality to prevent the postoperative infectious and noninfectious
      complications, enhance the immunity of host, and eventually improve the prognosis
      of gastrointestinal (GI) cancer patients undergoing surgery. However, different
      support routes, which are the optimum option, remain unclear. To evaluate the
      effects of different EIN support regimes for patients who underwent selective
      surgery for resectable GI malignancy, a Bayesian network meta-analysis (NMA) of
      randomized controlled trials (RCTs) was conducted. A search of PubMed, EMBASE,
      and the Cochrane Central Register of Controlled Trials (CENTRAL) was
      electronically searched until the end of December 2014. Moreover, we manually
      checked reference lists of eligible trials and review and retrieval unpublished
      literature. RCTs which investigated the comparative effects of EIN versus
      standard enteral nutrition (EN) or different EIN regimes were included if the
      clinical outcomes information can be extracted from it. A total of 27 RCTs were
      incorporated into this study. Pair-wise meta-analyses suggested that preoperative
      (relative risk [RR], 0.58; 95% confidence interval [CI], 0.43-0.78),
      postoperative (RR, 0.63; 95% CI, 0.52-0.76), and perioperative EIN methods (RR,
      0.46; 95% CI, 0.34-0.62) reduced incidence of postoperative infectious
      complications compared with standard EN. Moreover, perioperative EIN (RR, 0.65;
      95% CI, 0.44-0.95) reduced the incidence of postoperative noninfectious
      complications, and the postoperative (mean difference [MD], -2.38; 95% CI, -3.4
      to -1.31) and perioperative EIN (MD, -2.64; 95% CI, -3.28 to -1.99) also
      shortened the length of postoperative hospitalization compared with standard EN.
      NMA found that EIN support effectively improved the clinical outcomes of patients
      who underwent selective surgery for GI cancer compared with standard EN. Our
      results suggest EIN support is promising alternative for operation management in
      comparison with standard EN, and perioperative EIN regime is the optimum option
      for managing clinical status of patients who underwent selective surgery for GI
      cancer.

PMID- 26200649
TI  - Risk of Stroke-Associated Pneumonia With Acid-Suppressive Drugs: A Population
      Based Cohort Study.
AB  - Acid-suppressive drugs, including histamine-2 receptor antagonists (H2RAs) and
      proton pump inhibitors (PPIs), are common medications used for treating upper
      gastrointestinal tract disorders. However, acid-suppressive drugs have been
      reported to increase the risk of pneumonia in numerous disease populations.
      However, the relationship between acid-suppressive drugs and stroke-associated
      pneumonia (SAP) remains controversial. The purpose of this study was to
      investigate the association between acid-suppressive drug usage and pneumonia
      among patients with stroke by using a nationwide data set. A population-based
      cohort study was conducted using a data set from the Taiwanese National Health
      Insurance Research Database. Data on patients with new-onset stroke from 2010 to
      2011 were collected. Patients with and without acid-suppressive drug usage were
      followed up to identify the occurrence of any type of pneumonia. We estimated the
      adjusted hazard ratios (HRs) by using the Cox proportional hazards model. The
      study cohort comprised 7965 patients with new-onset stroke. The incidence of
      pneumonia was 6.9% (552/7965) and more than 40% (225/552) of patients developed
      pneumonia within 3 months after an acute stroke. Acid-suppressive drug usage was
      an independent risk factor of pneumonia. The adjusted HR for the risk of
      pneumonia in patients with new-onset stroke using acid-suppressive drugs was 1.44
      (95% confidence interval [CI] = 1.18-1.75, P < 0.01). Only PPI usage increased
      risk of chronic SAP (adjusted HR = 1.46, 95% CI = 1.04-2.05). Acid-suppressive
      drug usage was associated with a slightly increased risk of SAP. Physicians
      should exercise caution when prescribing acid-suppressive drugs to patients with
      stroke, particularly at the chronic stage.

PMID- 26200650
TI  - Accumulation of gamma-aminobutyric acid by Enterococcus avium 9184 in scallop
      solution in a two-stage fermentation strategy.
AB  - In this study, a new bacterial strain having a high ability to produce gamma
      aminobutyric acid (GABA) was isolated from naturally fermented scallop solution
      and was identified as Enterococcus avium. To the best of our knowledge, this is
      the first study to prove that E. avium possesses glutamate decarboxylase
      activity. The strain was then mutagenized with UV radiation and was designated as
      E. avium 9184. Scallop solution was used as the culture medium to produce GABA. A
      two-stage fermentation strategy was applied to accumulate GABA. In the first
      stage, cell growth was regulated. Optimum conditions for cell growth were pH,
      6.5; temperature, 37 degrees C; and glucose concentration, 10 g.L(-1) . This
      produced a maximum dry cell mass of 2.10 g.L(-1) . In the second stage, GABA
      formation was regulated. GABA concentration reached 3.71 g.L(-1) at 96 h pH 6.0,
      37 degrees C and initial l-monosodium glutamate concentration of 10 g.L(-1) .
      Thus, compared with traditional one-stage fermentation, the two-stage
      fermentation significantly increased GABA accumulation. These results provide
      preliminary data to produce GABA using E. avium and also provide a new approach
      to process and utilize shellfish.

PMID- 26200651
TI  - Advances in nickel-catalyzed cycloaddition reactions to construct carbocycles and
      heterocycles.
AB  - Transition-metal catalysis has revolutionized the field of organic synthesis by
      facilitating the construction of complex organic molecules in a highly efficient
      manner. Although these catalysts are typically based on precious metals,
      researchers have made great strides in discovering new base metal catalysts over
      the past decade. This Account describes our efforts in this area and details the
      development of versatile Ni complexes that catalyze a variety of cycloaddition
      reactions to afford interesting carbocycles and heterocycles. First, we describe
      our early work in investigating the efficacy of N-heterocyclic carbene (NHC)
      ligands in Ni-catalyzed cycloaddition reactions with carbon dioxide and
      isocyanate. The use of sterically hindered, electron donating NHC ligands in
      these reactions significantly improved the substrate scope as well as reaction
      conditions in the syntheses of a variety of pyrones and pyridones. The high
      reactivity and versatility of these unique Ni(NHC) catalytic systems allowed us
      to develop unprecedented Ni-catalyzed cycloadditions that were unexplored due to
      the inefficacy of early Ni catalysts to promote hetero-oxidative coupling steps.
      We describe the development and mechanistic analysis of Ni/NHC catalysts that
      couple diynes and nitriles to form pyridines. Kinetic studies and stoichiometric
      reactions confirmed a hetero-oxidative coupling pathway associated with this Ni
      catalyzed cycloaddition. We then describe a series of new substrates for Ni
      catalyzed cycloaddition reactions such as vinylcyclopropanes, aldehydes, ketones,
      tropones, 3-azetidinones, and 3-oxetanones. In reactions with vinycyclopropanes
      and tropones, DFT calculations reveal noteworthy mechanistic steps such as a C-C
      sigma-bond activation and an 8pi-insertion of vinylcyclopropane and tropone,
      respectively. Similarly, the cycloaddition of 3-azetidinones and 3-oxetanones
      also requires Ni-catalyzed C-C sigma-bond activation to form N- and O-containing
      heterocycles. 

PMID- 26200653
TI  - Plasma from chronic liver disease subjects exhibit differential ability to
      generate thrombin.
AB  - Liver fibrosis in chronic liver disease (CLD) results in complex alterations in
      procoagulant and anticoagulant proteins. Although an elevated international
      normalized ratio (INR) is a prominent feature of progressive fibrosis, the
      utility of the INR to accurately reflect the net effect of these changes on the
      coagulation system is uncertain. In subjects with CLD, elevated INRs have been
      observed in both bleeding and thrombotic complications, suggesting limitations of
      the INR in characterizing the coagulation status. Unlike the INR, which is
      preferentially sensitive to the extrinsic pathway, the direct measurement of
      thrombin generation better captures the global coagulation cascade. We conducted
      a pilot study measuring the INR, chromogenic factor X and thrombin generation in
      CLD subjects and compared them with control subjects and subjects on warfarin
      anticoagulation. We observed a large interquartile range in thrombin generation
      among compensated CLD subjects across a narrow INR range, suggesting that the INR
      is a suboptimal surrogate measure of thrombin generation in CLD subjects. 

PMID- 26200652
TI  - Association of systemic lupus erythematosus with decreased immunosuppressive
      potential of the IgG glycome.
AB  - OBJECTIVE: Glycans attached to the Fc portion of IgG are important modulators of
      IgG effector functions. Interindividual differences in IgG glycome composition
      are large and they associate strongly with different inflammatory and autoimmune
      diseases. IKZF1, HLA-DQ2A/B, and BACH2 genetic loci that affect IgG glycome
      composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a
      potentially causative role of aberrant IgG glycosylation in SLE. We undertook
      this large multicenter case-control study to determine whether SLE is associated
      with altered IgG glycosylation. METHODS: Using ultra-performance liquid
      chromatography analysis of released glycans, we analyzed the composition of the
      IgG glycome in 261 SLE patients and 247 matched controls of Latin American
      Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of
      different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE
      patients and 105 controls from China). RESULTS: Multiple statistically
      significant differences in IgG glycome composition were observed between patients
      and controls. The most significant changes included decreased galactosylation and
      sialylation of IgG (which regulate proinflammatory and antiinflammatory actions
      of IgG) as well as decreased core fucose and increased bisecting N
      acetylglucosamine (which affect antibody-dependent cell-mediated cytotoxicity).
      CONCLUSION: The IgG glycome in SLE patients is significantly altered in a way
      that decreases immunosuppressive action of circulating immunoglobulins. The
      magnitude of observed changes is associated with the intensity of the disease,
      indicating that aberrant IgG glycome composition or changes in IgG glycosylation
      may be an important molecular mechanism in SLE.

PMID- 26200654
TI  - Spontaneous Cell Competition in Immortalized Mammalian Cell Lines.
AB  - Cell competition is a form of cell-cell interaction by which cells compare
      relative levels of fitness, resulting in the active elimination of less-fit
      cells, "losers," by more-fit cells, "winners." Here, we show that in three
      routinely-used mammalian cell lines - U2OS, 3T3, and MDCK cells - sub-clones
      arise stochastically that exhibit context-dependent competitive behavior.
      Specifically, cell death is elicited when winner and loser sub-clones are
      cultured together but not alone. Cell competition and elimination in these cell
      lines is caspase-dependent and requires cell-cell contact but does not require de
      novo RNA synthesis. Moreover, we show that the phenomenon involves differences in
      cellular metabolism. Hence, our study demonstrates that cell competition is a
      common feature of immortalized mammalian cells in vitro and implicates cellular
      metabolism as a mechanism by which cells sense relative levels of "fitness." 

PMID- 26200655
TI  - Mid-Season Estimates of Influenza Vaccine Effectiveness against Influenza A(H3N2)
      Hospitalization in the Elderly in Quebec, Canada, January 2015.
AB  - BACKGROUND: The 2014/15 influenza season in Canada was characterized by an early
      epidemic due to vaccine-mismatched influenza A(H3N2) viruses, disproportionately
      affecting elderly individuals >=65-years-old. We assessed vaccine effectiveness
      (VE) against A(H3N2) hospitalization among elderly individuals during the peak
      weeks of the 2014/15 epidemic in Quebec, Canada. METHODS: Nasal specimens and
      clinical/epidemiological data were collected within 7 days of illness onset from
      elderly patients admitted with respiratory symptoms to one of four participating
      hospitals between November 30, 2014 and January 13, 2015. Cases tested RT-PCR
      positive for influenza A(H3N2) and controls tested negative for any influenza. VE
      was assessed by test-negative case-control design. RESULTS: There were 314
      participants including 186 cases (62% vaccinated) and 128 controls (59%
      vaccinated) included in primary VE analysis. Median age was 81.5 years, two
      thirds were admitted from the community and 91% had underlying comorbidity. Crude
      VE against A(H3N2) hospitalization was -17% (95%CI: -86% to 26%), decreasing to 
      23% (95%CI: -99 to 23%) with adjustment for age and comorbidity, and to -39%
      (95%CI: -142 to 20%) with additional adjustment for specimen collection interval,
      calendar time, type of residence and hospital. In sensitivity analyses, VE
      estimates were improved toward the null with restriction to participants admitted
      from the community (-2%; 95%CI: -105 to 49%) or with specimen collection <=4 days
      since illness onset (- 8%; 95%CI: -104 to 43%) but further from the null with
      restriction to participants with comorbidity (-51%; 95%CI: -169 to 15%).
      CONCLUSION: The 2014/15 mismatched influenza vaccine provided elderly patients
      with no cross-protection against hospitalization with the A(H3N2) epidemic
      strain, reinforcing the need for adjunct protective measures among high-risk
      individuals and improved vaccine options.

PMID- 26200656
TI  - Musical Preferences are Linked to Cognitive Styles.
AB  - Why do we like the music we do? Research has shown that musical preferences and
      personality are linked, yet little is known about other influences on preferences
      such as cognitive styles. To address this gap, we investigated how individual
      differences in musical preferences are explained by the empathizing-systemizing
      (E-S) theory. Study 1 examined the links between empathy and musical preferences
      across four samples. By reporting their preferential reactions to musical
      stimuli, samples 1 and 2 (Ns = 2,178 and 891) indicated their preferences for
      music from 26 different genres, and samples 3 and 4 (Ns = 747 and 320) indicated
      their preferences for music from only a single genre (rock or jazz). Results
      across samples showed that empathy levels are linked to preferences even within
      genres and account for significant proportions of variance in preferences over
      and above personality traits for various music-preference dimensions. Study 2 (N
      = 353) replicated and extended these findings by investigating how musical
      preferences are differentiated by E-S cognitive styles (i.e., 'brain types').
      Those who are type E (bias towards empathizing) preferred music on the Mellow
      dimension (R&B/soul, adult contemporary, soft rock genres) compared to type S
      (bias towards systemizing) who preferred music on the Intense dimension (punk,
      heavy metal, and hard rock). Analyses of fine-grained psychological and sonic
      attributes in the music revealed that type E individuals preferred music that
      featured low arousal (gentle, warm, and sensual attributes), negative valence
      (depressing and sad), and emotional depth (poetic, relaxing, and thoughtful),
      while type S preferred music that featured high arousal (strong, tense, and
      thrilling), and aspects of positive valence (animated) and cerebral depth
      (complexity). The application of these findings for clinicians, interventions,
      and those on the autism spectrum (largely type S or extreme type S) are
      discussed. 

PMID- 26200657
TI  - Liquid Phase Exfoliation of Two-Dimensional Materials by Directly Probing and
      Matching Surface Tension Components.
AB  - Exfoliation of two-dimensional (2D) materials into mono- or few layers is of
      significance for both fundamental studies and potential applications. In this
      report, for the first time surface tension components were directly probed and
      matched to predict solvents with effective liquid phase exfoliation (LPE)
      capability for 2D materials such as graphene, h-BN, WS2, MoS2, MoSe2, Bi2Se3,
      TaS2, and SnS2. Exfoliation efficiency is enhanced when the ratios of the surface
      tension components of the applied solvent is close to that of the 2D material in
      question. We enlarged the library of low-toxic and common solvents for LPE. Our
      study provides distinctive insight into LPE and has pioneered a rational strategy
      for LPE of 2D materials with high yield. 

PMID- 26200658
TI  - Medication Use before, during, and after Pregnancy among Women with Eating
      Disorders: A Study from the Norwegian Mother and Child Cohort Study.
AB  - INTRODUCTION: Little is known about medication use among women with eating
      disorders in relation to pregnancy. AIMS: To explore patterns of and associations
      between use of psychotropic, gastrointestinal and analgesic medications and
      eating disorders in the period before, during and after pregnancy. METHOD: This
      study is based on the Norwegian Mother and Child Cohort Study (MoBa). A total of
      62,019 women, enrolled at approximately 17 weeks' gestation, had valid data from
      the Norwegian Medical Birth Registry and completed three MoBa questionnaires. The
      questionnaires provided diagnostic information on broadly defined anorexia
      nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED) and recurrent
      self-induced purging in the absence of binge eating (EDNOS-P), along with self
      reported use of medication six months before, during, and 0-6 months after
      pregnancy. RESULTS: The prevalence of eating disorder subtypes before and/or
      during pregnancy was: 0.09% AN (n = 54), 0.94% BN (n = 585), 0.10% EDNOS-P (n =
      61) and 5.00% BED (n = 3104). The highest over-time prevalence of psychotropic
      use was within the AN (3.7-22.2%) and EDNOS-P (3.3-9.8%) groups. Compared to
      controls, BN was directly associated with incident use of psychotropics in
      pregnancy (adjusted RR: 2.25, 99% CI: 1.17-4.32). Having AN (adjusted RR: 5.11,
      99% CI: 1.53-17.01) or EDNOS-P (adjusted RR: 6.77, 99% CI: 1.41-32.53) was
      directly associated with use of anxiolytics/sedatives postpartum. The estimates
      of use of analgesics (BED) and laxatives (all eating disorders subtypes) were
      high at all time periods investigated. CONCLUSIONS: Use of psychotropic,
      gastrointestinal, and analgesic medications is extensive among women with eating
      disorders in the period around pregnancy. Female patients with eating disorders
      should receive evidence-based counseling about the risk of medication exposure
      versus the risk of untreated psychiatric illness during pregnancy and postpartum.

PMID- 26200660
TI  - Participating in a Citizen Science Monitoring Program: Implications for
      Environmental Education.
AB  - Tourism is of growing economical importance to many nations, in particular for
      developing countries. Although tourism is an important economic vehicle for the
      host country, its continued growth has led to on-going concerns about its
      environmental sustainability. Coastal and marine tourism can directly affect the
      environment through direct and indirect tourist activities. For these reasons
      tourism sector needs practical actions of sustainability. Several studies have
      shown how education minimizes the impact on and is proactive for, preserving the
      natural resources. This paper evaluates the effectiveness of a citizen science
      program to improve the environmental education of the volunteers, by means of
      questionnaires provided to participants to a volunteer-based Red Sea coral reef
      monitoring program (STEproject). Fifteen multiple-choice questions evaluated the
      level of knowledge on the basic coral reef biology and ecology and the awareness
      on the impact of human behaviour on the environment. Volunteers filled in
      questionnaires twice, once at the beginning, before being involved in the project
      and again at the end of their stay, after several days participation in the
      program. We found that the participation in STEproject significantly increased
      both the knowledge of coral reef biology and ecology and the awareness of human
      behavioural impacts on the environment, but was more effective on the former. We
      also detected that tourists with a higher education level have a higher initial
      level of environmental education than less educated people and that the project
      was more effective on divers than snorkelers. This study has emphasized that
      citizen science projects have an important and effective educational value and
      has suggested that tourism and diving stakeholders should increase their
      commitment and efforts to these programs. 

PMID- 26200661
TI  - Is Impact of Statin Therapy on All-Cause Mortality Different in HIV-Infected
      Individuals Compared to General Population? Results from the FHDH-ANRS CO4
      Cohort.
AB  - BACKGROUND: The effect of statins on all-cause mortality in the general
      population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention.
      Reported values in HIV-infected individuals have been discordant. We assessed the
      impact of statin-based primary prevention on all-cause mortality among HIV
      infected individuals. METHODS: Patients were selected among controls from a
      multicentre nested case-control study on the risk of myocardial infarction.
      Patients with prior cardiovascular or cerebrovascular disorders were not
      eligible. Potential confounders, including variables that were associated either
      with statin use and/or death occurrence and statin use were evaluated within the
      last 3 months prior to inclusion in the case-control study. Using an intention to
      continue approach, multiple imputation of missing data, Cox's proportional hazard
      models or propensity based weighting, the impact of statins on the 7-year all
      cause mortality was evaluated. RESULTS: Among 1,776 HIV-infected individuals, 138
      (8%) were statins users. During a median follow-up of 53 months, 76 deaths
      occurred, including 6 in statin users. Statin users had more cardiovascular risk
      factors and a lower CD4 T cell nadir than statin non-users. In univariable
      analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI
      0.53-2.82). The confounders accounted for were age, HIV transmission group,
      current CD4 T cell count, haemoglobin level, body mass index, smoking status,
      anti-HCV antibodies positivity, HBs antigen positivity, diabetes and
      hypertension. In the Cox multivariable model the estimated hazard ratio of statin
      on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83
      (95%CI 0.51-1.35) using inverse probability treatment weights. CONCLUSION: The
      impact of statin for primary prevention appears similar in HIV-infected
      individuals and in the general population.

PMID- 26200659
TI  - Soybean Oil Is More Obesogenic and Diabetogenic than Coconut Oil and Fructose in
      Mouse: Potential Role for the Liver.
AB  - The obesity epidemic in the U.S. has led to extensive research into potential
      contributing dietary factors, especially fat and fructose. Recently, increased
      consumption of soybean oil, which is rich in polyunsaturated fatty acids (PUFAs),
      has been proposed to play a causal role in the epidemic. Here, we designed a
      series of four isocaloric diets (HFD, SO-HFD, F-HFD, F-SO-HFD) to investigate the
      effects of saturated versus unsaturated fat, as well as fructose, on obesity and
      diabetes. C57/BL6 male mice fed a diet moderately high in fat from coconut oil
      and soybean oil (SO-HFD, 40% kcal total fat) showed statistically significant
      increases in weight gain, adiposity, diabetes, glucose intolerance and insulin
      resistance compared to mice on a diet consisting primarily of coconut oil (HFD).
      They also had fatty livers with hepatocyte ballooning and very large lipid
      droplets as well as shorter colonic crypt length. While the high fructose diet (F
      HFD) did not cause as much obesity or diabetes as SO-HFD, it did cause rectal
      prolapse and a very fatty liver, but no balloon injury. The coconut oil diet
      (with or without fructose) increased spleen weight while fructose in the presence
      of soybean oil increased kidney weight. Metabolomics analysis of the liver showed
      an increased accumulation of PUFAs and their metabolites as well as gamma
      tocopherol, but a decrease in cholesterol in SO-HFD. Liver transcriptomics
      analysis revealed a global dysregulation of cytochrome P450 (Cyp) genes in SO-HFD
      versus HFD livers, most notably in the Cyp3a and Cyp2c families. Other genes
      involved in obesity (e.g., Cidec, Cd36), diabetes (Igfbp1), inflammation (Cd63),
      mitochondrial function (Pdk4) and cancer (H19) were also upregulated by the
      soybean oil diet. Taken together, our results indicate that in mice a diet high
      in soybean oil is more detrimental to metabolic health than a diet high in
      fructose or coconut oil. 

PMID- 26200662
TI  - Europium, uranyl, and thorium-phenanthroline amide complexes in acetonitrile
      solution: an ESI-MS and DFT combined investigation.
AB  - The tetradentate N,N'-diethyl-N,N'-ditolyl-2,9-diamide-1,10-phenanthroline (Et
      Tol-DAPhen) ligand with hard-soft donor atoms has been demonstrated to be
      promising for the group separation of actinides from highly acidic nuclear
      wastes. To identify the formed complexes of this ligand with actinides and
      lanthanides, electrospray ionization mass spectrometry (ESI-MS) combined with
      density functional theory (DFT) calculations was used to probe the possible
      complexation processes. The 1 : 2 Eu-L species ([EuL2(NO3)](2+)) can be observed
      in ESI-MS at low metal-to-ligand ([M]/[L]) ratios, whereas the 1 : 1 Eu-L species
      ([EuL(NO3)2](+)) can be observed when the [M]/[L] ratio is higher than 1.0.
      However, ([UO2L(NO3)](+)) is the only detected species for the uranyl complexes.
      The [ThL2(NO3)2](2+) species can be observed at low [M]/[L] ratios; the 1 : 2
      species ([ThL2(NO3)](3+)) and a new 1 : 1 species ([ThL(NO3)3](+)) can be
      detected at high [M]/[L] ratios. Collision-induced dissociation (CID) results
      showed that Et-Tol-DAPhen ligands can coordinate strongly with metal ions, and
      the coordination moieties remain intact under CID conditions. Natural bond
      orbital (NBO), molecular electrostatic potential (MEP), electron localization
      function (ELF), atoms in molecules (AIM) and molecular orbital (MO) analyses
      indicated that the metal-ligand bonds of the actinide complexes exhibited more
      covalent character than those of the lanthanide complexes. In addition, according
      to thermodynamic analysis, the stable cationic M-L complexes in acetonitrile are
      found to be in good agreement with the ESI-MS results. 

PMID- 26200663
TI  - Obesity Is a Positive Modulator of IL-6R and IL-6 Expression in the Subcutaneous
      Adipose Tissue: Significance for Metabolic Inflammation.
AB  - The role of IL-6R/IL-6 axis in metabolic inflammation remains controversial. We
      determined the changes in adipose tissue expression of IL-6R and IL-6 in obese,
      overweight, and lean non-diabetic individuals. Subcutaneous adipose tissue
      biopsies were collected from 33 obese, 22 overweight, and 10 lean individuals and
      the expression of IL-6R, IL-6, TNF-alpha, MCP-1, IP-10, CD11b, CD163, and CD68
      was detected by immunohistochemistry; results were also confirmed by real-time RT
      PCR and confocal microscopy. The data were compared using unpaired t-test and the
      dependence between two variables was assessed by Pearson's correlation test.
      Obese individuals showed higher IL-6R expression (103.8+/-4.807) in the adipose
      tissue as compared with lean/overweight (68.06+/-4.179) subjects (P<0.0001). The
      elevated IL-6R expression correlated positively with body mass index (BMI)
      (r=0.80 P<0.0001) and percent body fat (r=0.69 P=0.003). The increased IL-6R
      expression in obesity was also confirmed by RT-PCR (Obese: 3.921+/-0.712 fold;
      Lean/Overweight: 2.191+/-0.445 fold; P=0.0453) and confocal microscopy. IL-6
      expression was also enhanced in obese adipose tissue (127.0+/-15.91) as compared
      with lean/overweight (86.69+/-5.25) individuals (P=0.03) which correlated
      positively with BMI (r=0.58 P=0.008). IL-6 mRNA expression was concordantly
      higher in obese (16.60+/-2.214 fold) versus lean/overweight (9.376+/-1.656 fold)
      individuals (P=0.0108). These changes in the IL-6R/IL-6 expression correlated
      positively with the adipose tissue expression of CD11b (IL-6R r=0.44 P=0.063; IL
      6 r=0.77 P<0.0001), CD163 (IL-6R r=0.45 P=0.045; IL-6 r=0.55 P=0.013), TNF-alpha
      (IL-6R r=0.73 P=0.0003; IL-6 r=0.60 P=0.008), MCP-1 (IL-6R r=0.61 P=0.005; IL-6
      r=0.63 P=0.004) and IP-10 (IL-6R r=0.41 P=0.08; IL-6 r=0.50 P=0.026). It was,
      therefore, concluded that obesity was a positive modulator of IL-6R and IL-6
      expression in the adipose tissue which might be a contributory mechanism to
      induce metabolic inflammation. 

PMID- 26200664
TI  - Palladium-Catalyzed Dearomative Cyclocarbonylation by C-N Bond Activation.
AB  - A fundamentally novel approach to bioactive quinolizinones is based on the
      palladium-catalyzed intramolecular cyclocarbonylation of allylamines.
      [Pd(Xantphos)I2 ], which features a very large bite angle, has been found to
      facilitate the rapid carbonylation of azaarene-substituted allylamines into
      bioactive quinolizinones in good to excellent yields. This transformation
      represents the first dearomative carbonylation and is proposed to proceed by
      palladium-catalyzed C?N bond activation, dearomatization, CO insertion, and a
      Heck reaction. 

PMID- 26200665
TI  - Anthropogenic Black Carbon Emission Increase during the Last 150 Years at Coastal
      Jiangsu, China.
AB  - Black carbon (BC) is one of the major drivers of climate change and a useful
      indicator of environmental pollution from industrialization, and thus it is
      essential to reconstruct the historical trend in BC flux to better understand its
      impact. The Yancheng coastal wetland reserve in Jiangsu province is an area
      sensitive to global sea level change and is also located in the most developed as
      well as most polluted region of China. We investigated the concentration and
      historical flux of BC over the past 150 years through geochemical analysis of two
      210Pb-dated sediment cores from Yancheng coastal wetland. Measured BC contents
      ranged from 0.24 mg g-1 to 1.41 mg g-1 with average values of 0.51mg g-1-0.69 mg
      g-1, and BC fluxes ranged from 0.69 g m-2 yr-1 to 11.80 g m-2 yr-1 with averages
      of 2.94g m-2 yr-1-3.79 g m-2 yr-1. These values are consistent with other records
      worldwide. Both BC content and flux show a gradual and continuous increase over
      time and clearly reflect increased emissions from anthropogenic activities. The
      BC records have a significant peak in recent years (from 2000 to 2007), which is
      accompanied by the sharp increase of energy consumption and total carbon emission
      in the region. It is reasonable to conclude that changes in BC from increasing
      human activities have controlled BC fluxes during the last 150 years. Industrial
      contamination, especially BC emission, in the coastal region of eastern China
      should be taken into account when developing management strategies for protecting
      the natural environment. 

PMID- 26200666
TI  - Correction: Neuroprotection by Argon Ventilation after Perinatal Asphyxia: A
      Safety Study in Newborn Piglets.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0113575.]. 

PMID- 26200667
TI  - Fundamental Time Scales Governing Organic Aerosol Multiphase Partitioning and
      Oxidative Aging.
AB  - Traditional descriptions of gas-particle partitioning of organic aerosols (OA)
      rely solely on thermodynamic properties (e.g., volatility). Under realistic
      conditions where phase partitioning is dynamic rather than static, the
      transformation of OA involves the interplay of multiphase partitioning with
      oxidative aging. A key challenge remains in quantifying the fundamental time
      scales for evaporation and oxidation of semivolatile OA. In this paper, we use
      isomer-resolved product measurements of a series of normal-alkanes (C18, C20,
      C22, and C24) to distinguish between gas-phase and heterogeneous oxidation
      products formed by reaction with hydroxyl radicals (OH). The product isomer
      distributions when combined with kinetics measurements of evaporation and
      oxidation enable a quantitative description of the multiphase time scales to be
      simulated using a single-particle kinetic model. Multiphase partitioning and
      oxidative transformation of semivolatile normal-alkanes under laboratory
      conditions is largely controlled by the particle phase state, since the time
      scales of heterogeneous oxidation and evaporation are found to occur on competing
      time scales (on the order of 10(-1) h). This is in contrast to atmospheric
      conditions where heterogeneous oxidation time scales are expected to be much
      longer (on the order of 10(2) h), with gas-phase oxidation being the dominant
      process regardless of the evaporation kinetics. Our results demonstrate the
      dynamic nature of OA multiphase partitioning and oxidative aging and reveal that
      the fundamental time scales of these processes are crucial for reliably extending
      laboratory measurements of OA phase partitioning and aging to the atmosphere.

PMID- 26200669
TI  - Stephen J. Lepore & Joshua M. Smyth (Eds.) (2002). The Writing Cure: How
      Expressive Writing Promotes Health and Emotional Well-Being. By Bela Buda.

PMID- 26200670
TI  - James E. Hendricks & Bryan D. Bryers (Eds.) (2002). Crisis Intervention in
      Criminal Justice/Social Service. By Bela Buda.

PMID- 26200668
TI  - Lipopeptide-Coated Iron Oxide Nanoparticles as Potential Glycoconjugate-Based
      Synthetic Anticancer Vaccines.
AB  - Although iron oxide magnetic nanoparticles (NPs) have been widely utilized in
      molecular imaging and drug delivery studies, they have not been evaluated as
      carriers for glycoconjugate-based anticancer vaccines. Tumor-associated
      carbohydrate antigens (TACAs) are attractive targets for the development of
      anticancer vaccines. Due to the weak immunogenicity of these antigens, it is
      highly challenging to elicit strong anti-TACA immune responses. With their high
      biocompatibilities and large surface areas, magnetic NPs were synthesized for
      TACA delivery. The magnetic NPs were coated with phospholipid-functionalized TACA
      glycopeptides through hydrophobic-hydrophobic interactions without the need for
      any covalent linkages. Multiple copies of glycopeptides were presented on NPs,
      potentially leading to enhanced interactions with antibody-secreting B cells
      through multivalent binding. Mice immunized with the NPs generated strong
      antibody responses, and the glycopeptide structures important for high antibody
      titers were identified. The antibodies produced were capable of recognizing both
      mouse and human tumor cells expressing the glycopeptide, resulting in tumor cell
      death through complement-mediated cytotoxicities. These results demonstrate that
      magnetic NPs can be a new and simple platform for multivalently displaying TACA
      and boosting anti-TACA immune responses without the need for a typical protein
      carrier. 

PMID- 26200671
TI  - Capillary electrophoresis method for speciation of iron (II) and iron (III) in
      pharmaceuticals by dual precapillary complexation.
AB  - Pharmaceutical iron sucrose is an iron (III) replacement for the treatment of
      iron deficiency anemia in patients with chronic kidney disease. The drug product
      (injection) is a colloidal solution of ferric hydroxide in complex with sucrose,
      containing 20 mg/mL elemental iron; according to United States pharmacopoeia
      (USP), the limit of iron (II) is 0.4% w/v. A selective CE method for the
      simultaneous determination of iron (III) and its potential impurity iron (II),
      was developed by applying a dual precapillary complexation. In particular, 1,10
      phenanthroline and 1,2-diaminocyclohexanetetraacetic acid were used for
      complexation of iron (II) and iron (III), respectively. Sample preparation was
      optimized to achieve mineralization of pharmaceuticals using HCl 6 M, by avoiding
      perturbation of the oxidation status of both iron species. Simple CZE conditions,
      involving a 60 mM (pH 9.3) tetraborate buffer at the constant voltage of 25 KV
      and 25 degrees C, allowed fast separation of iron (II) and iron (III) complexes
      that were detected at 265 nm. Sensitivity for iron (II) determination was found
      to be 4.80 MUM (LOQ) corresponding to 0.15% w/w with respect to the total iron
      test level. The method was validated by following International Conference on
      Harmonization guidelines for specificity, linearity, precision, accuracy, and
      robustness and it was applied to real pharmaceutical samples. The obtained
      results suggested that the method can be a useful alternative to the official USP
      and British pharmacopoeia polarographic method.

PMID- 26200672
TI  - Rheotaxis of spherical active particles near a planar wall.
AB  - For active particles the interplay between the self-generated hydrodynamic flow
      and an external shear flow, especially near bounding surfaces, can result in a
      rich behavior of the particles not easily foreseen from the consideration of the
      active and external driving mechanisms in isolation. For instance, under certain
      conditions, the particles exhibit "rheotaxis", i.e., they align their direction
      of motion with the plane of shear spanned by the direction of the flow and the
      normal of the bounding surface and move with or against the flow. To date,
      studies of rheotaxis have focused on elongated particles (e.g., spermatozoa), for
      which rheotaxis can be understood intuitively in terms of a "weather vane"
      mechanism. Here we investigate the possibility that spherical active particles,
      for which the "weather vane" mechanism is excluded due to the symmetry of the
      shape, may nevertheless exhibit rheotaxis. Combining analytical and numerical
      calculations, we show that, for a broad class of spherical active particles,
      rheotactic behavior may emerge via a mechanism which involves "self-trapping"
      near a hard wall owing to the active propulsion of the particles, combined with
      their rotation, alignment, and "locking" of the direction of motion into the
      shear plane. In this state, the particles move solely up- or downstream at a
      steady height and orientation. 

PMID- 26200673
TI  - Measuring the Long-term Impact of War-Zone Military Service Across Generations
      and Changing Posttraumatic Stress Disorder Definitions.

PMID- 26200674
TI  - New Family With Catecholaminergic Polymorphic Ventricular Tachycardia Linked to
      the Triadin Gene.
AB  - We describe a new family with cathecholaminergic polymorphic ventricular
      tachycardia (CPVT) linked to the Triadin gene. This is the second report of such
      a CPVT of autosomal recessive inheritance. Using an NGS panel including 42 genes
      involved in cardiac sudden death, 2 heterozygous pathogenic mutations (c.613C>
      T/p.Gln205* and c.22 + 29 A>G) were identified in the Triadin gene in 2 sibs who
      experienced early severe arrhythmias without evidence of CPVT diagnosis at first
      cardiac evaluation. However, significant arrhythmias occurred after
      catecholaminergic stimulation. Each of the TRDN mutations was inherited from a
      healthy parent. In this family, genetic studies permit confirmation of the CPVT
      diagnosis in the 2 affected sibs and permit the early diagnosis of the third
      asymptomatic child. It also helped guide the therapeutic strategy in this family.

PMID- 26200675
TI  - Transanal Mesorectal Excision: The New Challenge in Rectal Cancer.

PMID- 26200676
TI  - The American Society of Colon and Rectal Surgeons' Clinical Practice Guideline
      for the Treatment of Fecal Incontinence.

PMID- 26200677
TI  - Perineal or Abdominal Approach First During Intersphincteric Resection for Low
      Rectal Cancer: Which Is the Best Strategy?
AB  - BACKGROUND: Intersphincteric resection during total mesorectal excision for low
      rectal cancer can be performed through a primary abdominal or a primary perineal
      approach. OBJECTIVE: The purpose of this study was to compare the results of a
      primary perineal approach with those of a primary abdominal approach in patients
      undergoing laparoscopic total mesorectal excision for low rectal cancer. DESIGN:
      This was a case-matched retrospective study from a prospectively maintained
      database. SETTING: The study was conducted at a tertiary colorectal surgery
      referral center. PATIENTS: From 2005 to 2013, among 138 patients with low rectal
      cancer who underwent total mesorectal excision with intersphincteric resection,
      34 patients with a primary abdominal approach (abdominal group) were matched with
      51 identical patients with a primary perineal approach (6-cm perineal dissection
      along the mesorectal plane; perineal group), according to TNM stage, sex, BMI,
      and age. MAIN OUTCOMES MEASURES: Postoperative morbidity, oncologic outcomes, and
      3-year overall and disease-free survivals were measured. RESULTS: The operative
      time was significantly shorter in the perineal group (269 minutes in perineal vs
      240 minutes in abdominal group; p = 0.01). Overall morbidity (47% vs 47%; p =
      1.00), severe morbidity (16% vs 15%; p = 0.90), and clinical anastomotic leakage
      (24% vs 12%; p = 0.17) rates showed no differences when comparing the 2 groups.
      The overall R1 resection rate was similar in the 2 groups (16% vs 9%; p = 0.36),
      including a 10% vs 9% positive circumferential margin (p = 0.88) and a 8% vs 0%
      positive distal margin (p = 0.15). After a median follow-up of 39 months, 3-year
      overall (100% vs 93% (95% CI, 88%-98%); p = 0.26) and disease-free (63% (95% CI,
      56%-71%) vs 62% (95% CI, 53%-71%); p = 0.58) survival rates showed no differences
      between the 2 groups. LIMITATIONS: The study was limited by its nonrandomized
      nature and limited sample size. CONCLUSIONS: In cases of laparoscopic total
      mesorectal excision with intersphincteric resection for low rectal cancer, the
      primary perineal approach appears to reduce operative time and is associated with
      similar short- and long-term outcomes as compared with the primary abdominal
      approach. The primary perineal approach should thus be considered as the standard
      strategy.

PMID- 26200678
TI  - DNA Mismatch Repair Status Predicts Need for Future Colorectal Surgery for
      Metachronous Neoplasms in Young Individuals Undergoing Colorectal Cancer
      Resection.
AB  - BACKGROUND: The treatment of colorectal cancer in young patients involves both
      management of the incident cancer and consideration of the possibility of Lynch
      syndrome and the development of metachronous colorectal cancers. OBJECTIVE: This
      study aims to assess the prognostic role of DNA mismatch repair deficiency and
      extended colorectal resection for metachronous colorectal neoplasia risk in young
      patients with colorectal cancer. DESIGN, SETTING, AND PATIENTS: This is a
      retrospective review of 285 patients identified in our GI cancer registry with
      colorectal cancer diagnosed at 35 years or younger in the absence of polyposis.
      MAIN OUTCOME MEASURES: Using univariate and multivariate analysis, we assessed
      the prognostic role of mismatch repair deficiency and standard clinicopathologic
      characteristics, including the extent of resection, on the rate of developing
      metachronous colorectal neoplasia requiring resection. RESULTS: Mismatch repair
      deficiency was identified in biospecimens from 44% of patients and was
      significantly associated with an increased risk for metachronous colorectal
      neoplasia requiring resection (10-year cumulative risk, 13.5% +/- 4.2%) compared
      with 56% of patients with mismatch repair-intact colorectal cancer (10-year
      cumulative risk, 5.8% +/- 3.3%; p = 0.011). In multivariate analysis, mismatch
      repair deficiency was associated with a HR of 3.65 (95% CI, 1.44-9.21; p = 0.006)
      for metachronous colorectal neoplasia, whereas extended resection with ileorectal
      or ileosigmoid anastomosis significantly decreased the risk of metachronous
      colorectal neoplasia (HR, 0.21; 95% CI, 0.05-0.90; p = 0.036). LIMITATIONS: This
      study had a retrospective design, and, therefore, recommendations for colorectal
      cancer surgery and screening were not fully standardized. Quality of life after
      colorectal cancer surgery was not assessed. CONCLUSIONS: Young patients with
      colorectal cancer with molecular hallmarks of Lynch syndrome were at
      significantly higher risk for the development of subsequent colorectal neoplasia.
      This risk was significantly reduced in those who underwent extended resection
      compared with segmental resection.

PMID- 26200679
TI  - Effect of Multidisciplinary Cancer Conference on Treatment Plan for Patients With
      Primary Rectal Cancer.
AB  - BACKGROUND: Although multidisciplinary cancer conferences have been reported to
      lead to improved patient outcomes, few studies have reported results of these for
      rectal cancer. OBJECTIVE: The purpose of this work was to assess the quality of
      multidisciplinary cancer conferences, the effect of the conference on the initial
      treatment plan, compliance with the conference treatment recommendations, and
      clinical outcomes for rectal cancer. DESIGN: This was a prospective, longitudinal
      study. SETTINGS: The study was conducted at a tertiary care academic hospital.
      PATIENTS: Patients with primary rectal cancer were included in this study.
      INTERVENTION: The intervention was a rectal cancer-specific multidisciplinary
      cancer conference. MAIN OUTCOME MEASURES: The quality of the multidisciplinary
      cancer conference was assessed using the Cancer Care Ontario Multidisciplinary
      Cancer Conference standards score. A change in treatment plan was defined as a
      change from the initial treatment plan selected by the treating physician to an
      alternate treatment plan recommended at the conference. RESULTS: Twenty-five
      multidisciplinary cancer conferences were conducted over a 10-month study period.
      The Cancer Care Ontario Multidisciplinary Cancer Conference standards score was 7
      (from a maximum score of 9). Forty-two patients with primary rectal cancer were
      presented, and there was a 29% (12/42) change in the initial treatment plan. A
      total of 42% (5/12) of these changes were attributed to reinterpretation of the
      MRI findings. There was 100% compliance with the conference treatment
      recommendations. The circumferential resection margin was positive in 5.5%
      (2/36). LIMITATIONS: Selection bias may have led to an overestimate of effect,
      and there is no control group for comparison of clinical outcomes. CONCLUSIONS: A
      high-quality rectal cancer-specific multidisciplinary cancer conference led to a
      29% change in the treatment plan for patients with primary rectal cancer, with
      almost half of these changes attributed to reinterpretation of the magnetic
      resonance images.

PMID- 26200680
TI  - Oncologic and Clinicopathologic Outcomes of Robot-Assisted Total Mesorectal
      Excision for Rectal Cancer.
AB  - BACKGROUND: Minimally invasive rectal cancer surgery is challenging and
      technically difficult. Robotic technology offers a stable surgical platform with
      magnified 3-dimensional vision and endowristed instruments, which may facilitate
      the minimally invasive procedure. Data on short-term and long-term outcomes
      indicate results comparable to laparoscopic and open surgery. OBJECTIVE: We
      assessed the perioperative, clinicopathologic, and oncologic outcomes of robotic
      surgery for rectal cancer. DESIGN: This study was a review of a prospective
      database of patients over a 7-year period. SETTINGS: Procedures took place in the
      colorectal division at a tertiary hospital. PATIENTS: From August 2005 to October
      2012, 101 patients with rectal cancer were operated on using the robotic
      approach. Rectal cancers were defined as tumors within 15 cm from the anal verge.
      INTERVENTIONS: Patients received either a totally robotic or a hybrid
      laparoscopic-robotic operation with rectal dissection performed robotically. MAIN
      OUTCOME MEASURES: Operative and perioperative data, pathologic outcomes, and
      disease-free and overall survival were examined. RESULTS: There were 63 men
      (62.4%) and 38 women (37.6%) in the study; the mean age was 61.5 years. Mid
      rectal and low rectal cancers composed 74.2% of cases. Preoperative
      chemoradiation was given to 74.3% of patients. Four conversions to open surgery
      occurred. Circumferential margin positivity was 5%, and median lymph node yield
      was 15. At a mean follow-up of 34.9 months, the disease-free survival was 79.2%
      and overall survival 90.1%. The mean cost of robotic surgery was $22,640 versus
      $18,330 for the hand-assisted laparoscopic approach (p = 0.005). LIMITATIONS:
      This was a single-institution study with no head-to-head comparative group.
      CONCLUSIONS: Robotic surgery for rectal cancer extirpation is safe and feasible.
      It has a low conversion rate, satisfies all measures of pathologic adequacy, and
      offers acceptable oncologic outcomes. Robotic surgery is significantly more
      expensive than hand-assisted laparoscopic surgery. The absence of randomized data
      limits recommending it as the standard of care at present.

PMID- 26200681
TI  - Association of Comorbidity with Anastomotic Leak, 30-day Mortality, and Length of
      Stay in Elective Surgery for Colonic Cancer: A Nationwide Cohort Study.
AB  - BACKGROUND: Comorbidity has a negative influence on the long-term prognosis in
      patients with colorectal cancer, whereas its impact on the postoperative course
      is less clear. OBJECTIVES: The aim of this study was to investigate the influence
      of comorbidity on anastomotic leak and short-term outcomes after resection for
      colonic cancer. DESIGN: This is a retrospective nationwide cohort study SETTING:
      : Data were obtained from the Danish Colorectal Cancer Group and the National
      Patient Registry. PATIENTS: Patients with colonic cancer undergoing elective
      resection between 2001 and 2008 were selected. MAIN OUTCOME MEASURES: The primary
      outcome was the ability of comorbidity to predict anastomotic leak. Secondary
      outcomes were 30-day mortality and length of stay. Comorbidity was assessed by
      the Charlson Comorbidity Index. Multivariable logistic regression and receiver
      operating characteristics curves were used to adjust for confounding. RESULTS:
      The rate of anastomotic leak was 535/8597 (6.2%). The mean (95% CI) Charlson
      score was 0.83 (0.72-0.94) and 0.63 (0.61-0.66) for patients with and without
      anastomotic leak, p < 0.001. The Charlson score, as assessed in the multivariable
      analysis (adjusted OR, 1.07; 95% CI, 0.99-1.15; p = 0.077) and by receiver
      operating characteristics curves (area under the curve = 0.548), failed to
      predict anastomotic leak. Thirty-day mortality was 425/8587 (4.9%). In patients
      with anastomotic leakage, a Charlson score of >= 2 was associated with increased
      mortality in comparison with a Charlson score of <2 (adjusted HR, 1.58; 95% CI,
      1.00-2.51; p = 0.047). Mean length of stay was 8.7 days (95% CI, 8.4-9.2 days)
      for patients without an anastomotic leak in comparison with 23.3 days (95% CI,
      21.5-25.1 days) for patients with anastomotic leak and 25.5 days (95% CI, 21.7
      29.3 days) in patients with anastomotic leak and a Charlson score of >2, p <
      0.001. LIMITATIONS: This study is limited by the accuracy of the coding used to
      generate the Charlson Comorbidity Index and the retrospective study design.
      CONCLUSION: Comorbidity failed to predict anastomotic leak, but it was associated
      with an inferior short-term outcome in patients with this surgical complication.

PMID- 26200682
TI  - The Importance of a Minimal Tumor-Free Resection Margin in Locally Recurrent
      Rectal Cancer.
AB  - BACKGROUND: The importance of the circumferential resection margin has been
      demonstrated in primary rectal cancer, but the role of the minimal tumor-free
      resection margin in locally recurrent rectal cancer is unknown. OBJECTIVE: The
      purpose of this work was to evaluate the prognostic importance of a minimal tumor
      free resection margin in locally recurrent rectal cancer. DESIGN: This was a
      single-institution, retrospective study. SETTINGS: This study was conducted in a
      tertiary referral hospital. PATIENTS: Based on the final pathology report,
      surgically treated patients with locally recurrent rectal cancer between 1990 and
      2013 were divided into 4 groups: 1) tumor-free margins of >2 mm, 2) tumor-free
      margins of >0 to 2 mm, 3) microscopically involved margins, and 4)
      macroscopically involved margins. MAIN OUTCOME MEASURES: Local control and
      overall survival were the main outcome measures. RESULTS: A total of 174 patients
      with a median follow-up of 27 months (range, 0-144 months) were eligible for
      analysis. There was a significant difference in 5-year local re-recurrence-free
      survival in favor of 41 patients with tumor-free margins of >2 mm compared with
      34 patients with tumor-free margins of >0 to 2 mm (80% vs 62%; p = 0.03) and a
      significant difference in 5-year overall survival (60% vs 37%; p = 0.01). The 5
      year local re-recurrence-free and overall survival rates for 55 patients with
      microscopically involved margins were 28% and 16%, and for 20 patients with
      macroscopically involved margins the rates were 0% and 5%. On multivariable
      analysis, tumor-free margins of >0 to 2 mm were independently associated with
      higher re-recurrence rates (HR, 2.76 (95% CI, 1.06-7.16)) and poorer overall
      survival (HR, 2.57 (95% CI, 1.27-5.21)) compared with tumor-free margins of >2
      mm. LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS:
      Resection margin status is an independent prognostic factor for re-recurrence
      rate and overall survival in surgically treated, locally recurrent rectal cancer.
      In complete resections, patients with tumor-free resection margins of >0 to 2 mm
      have a higher re-recurrence rate and a poorer overall survival than patients with
      tumor-free resection margins of >2 mm.

PMID- 26200683
TI  - Early Removal of the Urinary Catheter After Total or Tumor-Specific Mesorectal
      Excision for Rectal Cancer Is Safe.
AB  - BACKGROUND: Total or tumor-specific mesorectal excision can preserve pelvic
      autonomic nerves during rectal cancer surgery and minimize urinary dysfunction.
      However, urinary catheterization several days in duration is a common practice
      after total or tumor-specific mesorectal excision. OBJECTIVE: This study aimed to
      evaluate the optimal duration of urinary catheterization after total or tumor
      specific mesorectal excision for rectal cancer. DESIGN: This is a retrospective
      review of patients who underwent total or tumor-specific mesorectal excision for
      rectal cancer. SETTINGS: This study was performed in the colorectal division of a
      university-affiliated hospital. PATIENTS: Between March 2009 and February 2013,
      236 patients fulfilled the inclusion criteria. Patients who underwent combined
      pelvic surgery and those who had postoperative complications with a Dindo grade
      III or more and a known urinary disease were excluded; the remaining 189 patients
      were evaluated. MAIN OUTCOME MEASURES: The primary outcome measure of this study
      was the incidence of postoperative urinary retention. RESULTS: The incidence of
      acute urinary retention was 4.8%. Urinary retention was not associated with the
      postoperative urinary catheterization duration (p = 0.99). Patients were assigned
      to 2 groups according to urinary catheterization duration (1 vs >= 2 days). No
      significant differences were observed between the 2 groups regarding urinary
      retention (4.8% for 1 day vs 4.7% for >= 2 days; p = 1.0). In a logistic
      regression analysis, age, sex, ASA classification, surgical procedure, surgical
      approach, stage, distance from the anal verge, rate of preoperative radiotherapy,
      duration of urinary catheterization, and time period of surgery were not
      associated with urinary retention. LIMITATIONS: This was a retrospective, single
      center study. There is potential for selection bias. CONCLUSIONS: Our study
      showed that the urinary catheter could be safely removed on the first
      postoperative day after total or tumor-specific mesorectal excision.

PMID- 26200684
TI  - Prospective Single-Center Observational Study of Routine Histopathologic
      Evaluation of Macroscopically Normal Hemorrhoidectomy and Fissurectomy Specimens
      in Search of Anal Intraepithelial Neoplasia.
AB  - BACKGROUND: The necessity for routine histopathologic evaluation of
      hemorrhoidectomy specimens considered free of suspicious areas after careful
      visual and manual inspection remains controversial. OBJECTIVE: The purpose of
      this work was to prospectively study the prevalence of anal intraepithelial
      neoplasia in macroscopically normal operative specimens. DESIGN AND PATIENTS:
      From October 2005 to September 2010, all hemorrhoidectomy and fissurectomy
      specimens were sent for routine histopathologic analysis. SETTING: This study was
      conducted at a tertiary referral center. MAIN OUTCOME MEASURES: The primary
      outcome measured was the histopathologic examination of surgical samples.
      RESULTS: Among the specimens from 2997 procedures, routine histopathologic
      evaluation found anal intraepithelial neoplasia in 97 patients (3.2%), despite
      the fact that visual and manual inspection had determined that the specimens were
      free of any suspected anal intraepithelial neoplasia or human papillomavirus
      related lesion. The pathological diagnoses for these macroscopically normal
      specimens were AIN1 in 22 (23%) patients, AIN2 in 48 (49%) patients and AIN3 in
      27 (28%) patients, making the prevalence of high-grade and low-grade disease 2.5%
      (anal intraepithelial neoplasia 2/3) and 0.7% (anal intraepithelial neoplasia 1).
      LIMITATIONS: This study was limited by being a single-center study. CONCLUSION:
      This prospective single-center study demonstrated that the prevalence of
      infraclinical anal intraepithelial neoplasia in macroscopically normal
      hemorrhoidectomy and fissurectomy specimens is not negligible (3.2% with 2.5%
      high-grade disease).

PMID- 26200685
TI  - Oral Mechanical Bowel Preparation for Colorectal Surgery: Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: Oral mechanical bowel preparation is often used before elective
      colorectal surgery to reduce postoperative complications. OBJECTIVE: The purpose
      of this study was to synthesize the evidence on the comparative effectiveness and
      safety of oral mechanical bowel preparation versus no preparation or enema. DATA
      SOURCES: We searched MEDLINE, the Cochrane Central Register of Controlled Trials,
      Embase, and CINAHL without any language restrictions (last search on September 6,
      2013). We also searched the US Food and Drug Administration Web site and
      ClinicalTrials.gov and supplemented our searches by asking technical experts and
      perusing reference lists. STUDY SELECTION: We included English-language, full
      text reports of randomized clinical trials and nonrandomized comparative studies
      of patients undergoing elective colon or rectal surgery. For adverse events we
      also included single-group cohort studies of at least 200 participants.
      INTERVENTIONS: Interventions included oral mechanical bowel preparation, oral
      mechanical bowel preparation plus enema, enema only, and no oral mechanical bowel
      preparation or enema. MAIN OUTCOME MEASURES: Anastomotic leakage, all-cause
      mortality, wound infection, peritonitis/intra-abdominal abscess, reoperation,
      surgical site infection, quality of life, length of stay, and adverse events were
      measured. We synthesized results across studies qualitatively and with Bayesian
      random-effects meta-analyses. RESULTS: A total of 18 randomized clinical trials,
      7 nonrandomized comparative studies, and 6 single-group cohorts were included. In
      meta-analyses of randomized clinical trials, the credibility intervals of the
      summary OR included the null value of 1.0 for comparisons of oral mechanical
      bowel preparation and either no oral preparation or enema for overall mortality,
      anastomotic leakage, wound infection, peritonitis, surgical site infection, and
      reoperation. These results were robust to extensive sensitivity analyses.
      Evidence on adverse events was sparse. LIMITATIONS: The study was limited by
      weaknesses in the underlying evidence, such as incomplete reporting of relevant
      information, exclusion of non-English and relevant unpublished studies, and
      possible missed indexing of nonrandomized studies. CONCLUSIONS: Our results could
      not exclude modest beneficial or harmful effects of oral mechanical bowel
      preparation compared with no preparation or enema.

PMID- 26200686
TI  - Ileum Interposition for Low Rectal Anastomosis in Rectal Cancer Surgery: Is It a
      Remedial Option?

PMID- 26200687
TI  - Ileum Interposition for Low Rectal Anastomosis in Rectal Cancer Surgery: Too Much
      Effort?

PMID- 26200688
TI  - The Use of PlasmaJet as a Novel Technique for Tissue Dissection in Complex
      Abdominal Surgery.

PMID- 26200689
TI  - Localizing Colonic Lesions.

PMID- 26200690
TI  - Abdominoperineal Excision: A Confusion in Terminology.

PMID- 26200691
TI  - The Authors Reply.

PMID- 26200692
TI  - Self-Assessment Quiz: Answers, Critiques, and References.

PMID- 26200694
TI  - Cold water cleaning of brain proteins, biofilm and bone - harnessing an
      ultrasonically activated stream.
AB  - In the absence of sufficient cleaning of medical instruments, contamination and
      infection can result in serious consequences for the health sector and remains a
      significant unmet challenge. In this paper we describe a novel cleaning system
      reliant on cavitation action created in a free flowing fluid stream where
      ultrasonic transmission to a surface, through the stream, is achieved using
      careful design and control of the device architecture, sound field and the
      materials employed. Cleaning was achieved with purified water at room
      temperature, moderate fluid flow rates and without the need for chemical
      additives or the high power consumption associated with conventional strategies.
      This study illustrates the potential in harnessing an ultrasonically activated
      stream to remove biological contamination including brain tissue from surgical
      stainless steel substrates, S. epidermidis biofilms from glass, and fat/soft
      tissue matter from bone structures with considerable basic and clinical
      applications. 

PMID- 26200695
TI  - What is the role of endoscopic retrograde cholangiopancreatography in assessing
      traumatic rupture of the pancreatic in children?
AB  - BACKGROUND AND STUDY AIMS: Trauma is one of the most common causes of morbidity
      and mortality in the pediatric population. The diagnosis of pancreatic injury is
      based on clinical presentation, laboratory and imaging findings, and endoscopic
      methods. CT scanning is considered the gold standard for diagnosing pancreatic
      trauma in children. PATIENTS AND METHODS: This retrospective study evaluates data
      from 25 pediatric patients admitted to the University Hospital Motol, Prague,
      with blunt pancreatic trauma between January 1999 and June 2013. RESULTS: The
      exact grade of injury was determined by CT scans in 11 patients (47.8%). All 25
      children underwent endoscopic retrograde cholangiopancreatography (ERCP). Distal
      pancreatic duct injury (grade III) was found in 13 patients (52%). Proximal
      pancreatic duct injury (grade IV) was found in four patients (16 %). Major
      contusion without duct injury (grade IIB) was found in six patients (24%). One
      patient experienced duodeno-gastric abruption not diagnosed on the CT scan. The
      diagnosis was made endoscopically during ERCP. Grade IIB pancreatic injury was
      found in this patient. One patient (4%) with pancreatic pseudocyst had a major
      contusion of pancreas without duct injury (grade IIA). Four patients (16%) with
      grade IIB, III and IV pancreatic injury were treated exclusively and
      nonoperatively with a pancreatic stent insertion and somatostatine. Two patients
      (8%) with a grade IIB injury were treated conservatively only with somatostatine
      without drainage. Eighteen (72 %) children underwent surgical intervention within
      24 h after ERCP. CONCLUSION: ERCP is helpful when there is suspicion of
      pancreatic duct injury in order to exclude ductal leakage and the possibility of
      therapeutic intervention. ERCP can speed up diagnosis of higher grade of
      pancreatic injuries.

PMID- 26200696
TI  - Dual pathways mediate beta-amyloid stimulated glutathione release from
      astrocytes.
AB  - Oxidative stress plays an important role in the progression of Alzheimer's
      disease (AD) and other neurodegenerative conditions. Glutathione (GSH), the major
      antioxidant in the central nervous system, is primarily synthesized and released
      by astrocytes. We determined if beta-amyloid (Abeta42), crucially involved in
      Alzheimer's disease, affected GSH release. Monomeric Abeta (mAbeta) stimulated
      GSH release from cultured cortical astrocytes more effectively than oligomeric
      Abeta (oAbeta) or fibrillary Abeta (fAbeta). Monomeric Abeta increased the
      expression of the transporter ABCC1 (also referred to as MRP1) that is the main
      pathway for GSH release. GSH release from astrocytes, with or without mAbeta
      stimulation, was reduced by pharmacological inhibition of ABCC1. Astrocytes
      robustly express connexin proteins, especially connexin43 (Cx43), and mAbeta also
      stimulated Cx43 hemichannel-mediated glutamate and GSH release. Abeta-stimulation
      facilitated hemichannel opening in the presence of normal extracellular calcium
      by reducing astrocyte cholesterol level. Abeta treatment did not alter the
      intracellular concentration of reduced or oxidized glutathione. Using a mouse
      model of AD with early onset Abeta deposition (5xFAD), we found that cortical
      ABCC1 was significantly increased in temporal register with the surge of Abeta
      levels in these mice. ABCC1 levels remained elevated from 1.5 to 3.5 months of
      age in 5xFAD mice, before plunging to subcontrol levels when amyloid plaques
      appeared. Similarly, in cultured astrocytes, prolonged incubation with aggregated
      Abeta, but not mAbeta, reduced induction of ABCC1 expression. These results
      support the hypothesis that in the early stage of AD pathogenesis, less
      aggregated Abeta increases GSH release from astrocytes (via ABCC1 transporters
      and Cx43 hemichannels) providing temporary protection from oxidative stress which
      promotes AD development.

PMID- 26200697
TI  - WHO classification 2008 of myeloproliferative neoplasms: a workshop learning
      effect--the Danish experience.
AB  - We examined the learning effect of a workshop for Danish hematopathologists led
      by an international expert regarding histological subtyping of myeloproliferative
      neoplasms (MPN). Six hematopathologists evaluated 43 bone marrow (BM) biopsies
      according to the WHO description (2008), blinded to clinical data. All panelists
      then participated in the workshop. The case biopsies - mixed with 251 other MPN
      BM biopsies - were reviewed again. Consensus regarding the histological subtype
      was significantly improved; from 49% to 72% (Fleiss kappa value 0.302 pre
      workshop, 0.474 post-workshop; p = 0.004). There was no significant effect on the
      isolated morphological characteristics. Agreement between cases with histological
      consensus and clinical diagnosis was 86% without significant change during
      workshop sessions. Our study demonstrates that experienced hematopathologists can
      significantly improve their diagnostic ability by a workshop led by an
      international expert; not by improving the evaluation of individual histological
      parameters but by weighting these in their conclusive diagnosis. 

PMID- 26200698
TI  - Orthotopic Osteogenecity Enhanced by a Porous Gelatin Sponge in a Critical-Sized
      Rat Calvaria Defect.
AB  - The gelatin (Gel) powders, derived from acidic and basic extractions of porcine
      dermis (referred to as AE and BE), were processed for the porous sponge
      preparation. The disks, which were less than or greater than 500 MUm in diameter
      [small (S) and large (L) pores, respectively] in both extractions and had an
      interconnected structure respectively, were implanted in critical-sized defects
      (CSD) of rat calvaria for 4 and 8 weeks to analyze the bone repair capability.
      Only the AE-S disk induced bone formation (over 60%) histomorphometrically in the
      CSD after 8 weeks, although the collagen orientation of the regenerated bone was
      still immature. Osteoblastic cell culture until 14 days did not substantiate
      marked superiority of AE-S disk regarding the proliferation and the
      differentiation, although the initial attachment was enhanced on AE-S disk than
      BE-L disk. The results provide the findings that a Gel sponge with a specific
      porous structure is capable of inducing orthotopic bone formation in vivo
      environment.

PMID- 26200699
TI  - Urethrotomy of the glans penis in three male dogs with urolithiasis.
AB  - Three intact male dogs with stranguria and haematuria caused by uroliths in the
      penile urethra underwent urethrotomy using a novel surgical approach directly
      over the caudal part of the os penis because conservative procedures to resolve
      the obstructions had failed. Haemorrhage was minimal, and the incisions healed
      rapidly by second intention. Complications did not occur during the 6-month
      follow-up period. Urethrotomy directly over the os penis is straightforward,
      associated with few complications and holds promise for the removal of urinary
      calculi in the penile urethra. 

PMID- 26200700
TI  - Using the Nudge and Shove Methods to Adjust Item Difficulty Values.
AB  - In any examination, it is important that a sufficient mix of items with varying
      degrees of difficulty be present to produce desirable psychometric properties and
      increase instructors' ability to make appropriate and accurate inferences about
      what a student knows and/or can do. The purpose of this "teaching tip" is to
      demonstrate how examination items can be affected by the quality of distractors,
      and to present a simple method for adjusting items to meet difficulty
      specifications. 

PMID- 26200701
TI  - Client Perspectives on Desirable Attributes and Skills of Veterinary
      Technologists in Australia: Considerations for Curriculum Design.
AB  - Client or service user perspectives are important when designing curricula for
      professional programs. In the case of veterinary technology, an emerging
      profession in the veterinary field in Australasia, client views on desirable
      graduate attributes, skills, and knowledge have not yet been explored. This study
      reports on a survey of 441 veterinary clients (with 104 responses) from four
      veterinary practices in Brisbane, Queensland, conducted between October 2008 and
      February 2009. The included veterinary practices provided clinical placements for
      veterinary technology undergraduates and employment for veterinary technology
      graduates (2003-2007). Client socio-demographic data along with ratings of the
      importance of a range of technical (veterinary nursing) skills, emotional
      intelligence, and professional attributes for veterinary technology graduates
      were collected and analyzed. Overall, the majority of clients viewed technical
      skills, emotional intelligence, and professional attributes as important in the
      clinical practice of veterinary technology graduates with whom they interacted in
      the veterinary practice. Client interviews (n=3) contextualized the survey data
      and also showed that clients attached importance to graduates demonstrating
      professional competence. Agglomerative hierarchical cluster analysis revealed
      four distinct groupings of clients within the data based on their differing
      perceptions. Using a multivariable proportional-odds regression model, it was
      also found that some client differences were influenced by demographic factors
      such as gender, age, and number of visits annually. For example, the odds of
      female clients valuing emotionality and sociability were greater than males.
      These findings provide useful data for the design of a professionalizing and
      market-driven veterinary technology curriculum. 

PMID- 26200702
TI  - Assessing Veterinary and Animal Science Students' Moral Judgment Development on
      Animal Ethics Issues.
AB  - Little has been done to assess veterinarians' moral judgment in relation to
      animal ethics issues. Following development of the VetDIT, a new moral judgment
      measure for animal ethics issues, this study aimed to refine and further validate
      the VetDIT, and to identify effects of teaching interventions on moral judgment
      and changes in moral judgment over time. VetDIT-V1 was refined into VetDIT-V2,
      and V3 was developed as a post-intervention test to prevent repetition. To test
      these versions for comparability, veterinary and animal science students (n=271)
      were randomly assigned to complete different versions. The VetDIT discriminates
      between stages of moral judgment, condensed into three schemas: Personal Interest
      (PI), Maintaining Norms (MN), and Universal Principles (UP). There were no
      differences in the scores for MN and UP between the versions, and we equated PI
      scores to account for differences between versions. Veterinary science students
      (n=130) who completed a three-hour small-group workshop on moral development
      theory and ethical decision making increased their use of UP in moral reasoning,
      whereas students (n=271) who received similar information in a 50-minute lecture
      did not. A longitudinal comparison of matched first- and third-year students
      (n=39) revealed no moral judgment development toward greater use of UP. The
      VetDIT is therefore useful for assessing moral judgment of animal and human
      ethics issues in veterinary and other animal-related professions. Intensive small
      group workshops using moral development knowledge and skills, rather than
      lectures, are conducive to developing veterinary students' moral judgment. 

PMID- 26200703
TI  - Recurrent hypoinsulinemic hyperglycemia in neonatal rats increases PARP-1 and NF
      kappaB expression and leads to microglial activation in the cerebral cortex.
AB  - BACKGROUND: Hyperglycemia is a common metabolic problem in extremely low-birth
      weight preterm infants. Neonatal hyperglycemia is associated with increased
      mortality and brain injury. Glucose-mediated oxidative injury may be responsible.
      Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme involved in DNA repair
      and cell survival. However, PARP-1 overactivation leads to cell death. NF-kappaB
      is coactivated with PARP-1 and regulates microglial activation. The effects of
      recurrent hyperglycemia on PARP-1/NF-kappaB expression and microglial activation
      are not well understood. METHODS: Rat pups were subjected to recurrent
      hypoinsulinemic hyperglycemia of 2 h duration twice daily from postnatal (P) day
      3-P12 and killed on P13. mRNA and protein expression of PARP-1/NF-kappaB and
      their downstream effectors were determined in the cerebral cortex. Microgliosis
      was determined using CD11 immunohistochemistry. RESULTS: Recurrent hyperglycemia
      increased PARP-1 expression confined to the nucleus and without causing PARP-1
      overactivation and cell death. NF-kappaB mRNA expression was increased, while
      IkappaB mRNA expression was decreased. inducible nitric oxide synthase (iNOS),
      endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase
      (nNOS) mRNA expressions were decreased. Hyperglycemia significantly increased the
      number of microglia. CONCLUSION: Recurrent hyperglycemia in neonatal rats is
      associated with upregulation of PARP-1 and NF-kappaB expression and subsequent
      microgliosis but not neuronal cell death in the cerebral cortex.

PMID- 26200704
TI  - Novel mutations of NFIX gene causing Marshall-Smith syndrome or Sotos-like
      syndrome: one gene, two phenotypes.
AB  - BACKGROUND: Only 15 point mutations in NFIX gene have been reported so far, nine
      of them cause the Marshall-Smith syndrome (MSS) and the remaining mutations lead
      to an overgrowth disorder with a less severe phenotype, defined as Sotos-like.
      METHODS: The clinical findings in three patients with MSS and two patients with a
      Sotos-like phenotype are presented. Analysis of the NFIX gene was performed both
      by conventional or next-generation sequencing. RESULTS: Five de novo mutations in
      NFIX gene were identified, four of them not previously reported. Two frameshift
      mutations and a donor-splice one caused MSS, while two missense mutations in the
      DNA binding/dimerisation domain entailed an overgrowth syndrome with some
      clinical features resembling Sotos syndrome, accompanied by a marfanoid habitus,
      very low BMI, long narrow face, or arachnodactyly. CONCLUSION: Marshall-Smith
      mutations are scattered through exons 6-10 of NFIX gene, while most point
      mutations causing an overgrowth syndrome are clustered in exon 2. Clinical
      features of this overgrowth syndrome may well be considered an intermediate
      phenotype between Sotos and Marfan syndromes.

PMID- 26200705
TI  - UGT1A1 gene mutations and neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and
      Han populations.
AB  - BACKGROUND: Uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1)
      gene mutation was shown to be responsible for neonatal hyperbilirubinemia. This
      study aimed to investigate whether UGT1A1 gene mutation is associated with
      neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations. METHODS:
      Two hundred and eighteen infants with hyperbilirubinemia (118 Heiyi Zhuang, 100
      Han) and 190 control subjects (110 Heiyi Zhuang, 80 Han) were enrolled.
      Polymerase chain reaction and gene sequencing were used to detect the TATA-box
      and exon 1 of UGT1A1. RESULTS: (TA)7 insertion mutation, 211G>A (G71R), 686C>A
      (P229Q), and 189C>T (D63D) were detected. Logistic regression analysis showed
      odds ratios (OR) of 2.64 (95% confidence interval (CI) 1.64-4.24; P < 0.001) and
      0.69 (95%CI 0.43-1.10; P = 0.115) for neonates who carried UGT1A1 G71R and (TA)7
      insertion mutation, respectively. G71R homozygosity increased the odds of
      dangerous bilirubin levels by a factor 34.23, and G71R heterozygosity only by
      2.10. CONCLUSION: We found that UGT1A1 G71R mutation is a risk factor for
      neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations.
      Meanwhile, the UGT1A1 (TA)7 insertion mutation is not associated with neonatal
      hyperbilirubinemia in the two ethnic groups.

PMID- 26200706
TI  - Relationship Between Physical Frailty and Low-Grade Inflammation in Late-Life
      Depression.
AB  - OBJECTIVES: To determine whether physical frailty is associated with low-grade
      inflammation in older adults with depression, because late-life depression is
      associated with physical frailty and low-grade inflammation. DESIGN: Baseline
      data of a cohort study. SETTING: Primary care and specialized mental health care.
      PARTICIPANTS: Individuals aged 60 and older with depression according to
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria
      (N = 366). MEASUREMENTS: The physical frailty phenotype, defined as three out of
      five criteria (weight loss, weakness, exhaustion, slowness, low physical activity
      level), and three inflammatory markers (C-reactive protein (CRP), interleukin-6
      (IL-6), and neutrophil gelatinase-associated lipocalin (NGAL)) were assessed.
      RESULTS: The physical frailty phenotype was not associated with inflammatory
      markers in linear regression models adjusted for sociodemographic
      characteristics, lifestyle characteristics, and somatic morbidity. Of the
      individual criteria, handgrip strength was associated with CRP (beta = -0.21, P =
      .002) and IL-6 (beta = -0.25, P < .001), and gait speed was associated with NGAL
      (beta = 0.15, P = .02). Principal component analysis identified two dimensions
      within the physical frailty phenotype: performance-based physical frailty
      (encompassing gait speed, handgrip strength, and low physical activity) and
      vitality-based physical frailty (encompassing weight loss and exhaustion). Only
      performance-based physical frailty was associated with higher levels of
      inflammatory markers (CRP: beta = 0.14, P = .03; IL-6: beta = 0.13, P = .06;
      NGAL: beta = 0.14, P = .03). CONCLUSION: The physical frailty phenotype is not a
      unidimensional construct in individuals with depression. Only performance-based
      physical frailty is associated with low-grade inflammation in late-life
      depression, which might point to a specific depressive subtype.

PMID- 26200707
TI  - What Will It Take to Cure HIV?
AB  - Investigational strategies to attempt HIV cure or remission include very early
      initiation of antiretroviral therapy to limit the latent HIV reservoir and
      preinfection vaccination. In the setting of viral suppression, strategies include
      reactivation of latently infected cells (eg, through "shock" therapy with histone
      deacetylase inhibitors or other agents); use of broadly neutralizing antibodies,
      therapeutic vaccines, immunotoxins, or other immune-based therapies to kill
      latently infected cells; and gene editing to induce target cell resistance (eg,
      by eliminating the CC chemokine receptor 5 [CCR5] coreceptor). Improved ability
      to detect and quantify very low levels of virus is needed. This article
      summarizes a presentation by Jintanat Ananworanich, MD, PhD, at the IAS-USA
      continuing education program held in New York, New York, in October 2014. 

PMID- 26200709
TI  - Hepatitis C Virus Direct-Acting Antiviral Drug Interactions and Use in Renal and
      Hepatic Impairment.
AB  - Direct-acting antiviral (DAA) drugs exhibit considerable variability in
      mechanisms of metabolism and the extent to which they are substrates, inhibitors,
      or inducers of cytochrome P450 enzymes or P-glycoprotein and other drug
      transporters. Thus, potential drug-drug interactions with other commonly used
      therapies also vary, as do the effects of renal and hepatic impairment on DAA
      drug exposure. Drug-drug interaction profiles and use in cases of renal or
      hepatic impairment are reviewed for the DAAs simeprevir; sofosbuvir; ledipasvir;
      the fixed-dose combination regimen of paritaprevir, ritonavir, and ombitasvir
      plus dasabuvir; and the investigational drugs daclatasvir and asunaprevir. This
      article summarizes a presentation by Lucas Hill, PharmD, at the IAS-USA
      continuing education program held in Chicago, Illinois, in October 2014. 

PMID- 26200708
TI  - Preexposure Prophylaxis For HIV Prevention: What We Know and What We Still Need
      to Know for Implementation.
AB  - Preexposure prophylaxis (PrEP) with tenofovir and emtricitabine has been shown to
      be effective and cost-effective in preventing acquisition of HIV infection.
      However, PrEP has not yet been widely adopted in the clinical practice setting.
      Data thus far, although imperfect, do not indicate an increase in risk behaviors
      in the setting of PrEP, although potential risk compensation outside of the
      clinical trial setting should be further examined. Substantial work remains to
      implement and support PrEP use, including identification of optimal settings for
      providing and managing PrEP, identification of methods to ensure optimal
      adherence to treatment, and employment of strategies to deliver PrEP to
      populations at greatest risk. This article summarizes a presentation made by
      Raphael J. Landovitz, MD, MSc, at the 2015 Conference on Retroviruses and
      Opportunistic Infections held from February 23 to February 26 in Seattle,
      Washington. 

PMID- 26200710
TI  - Will You Still Treat Me When I'm 64? Care of the Older Adult With HIV Infection.
AB  - HIV infection is associated with chronic immune activation that is superimposed
      on immunologic senescence in older adults, resulting in the acquisition of age
      related diseases at younger ages. The incidence of coronary artery disease is
      higher among HIV-infected persons than uninfected individuals matched for age and
      sex. HIV infection and its treatment have been associated with premature bone
      loss. Lung, hepatic, and anal cancers occur at younger ages in persons with HIV
      infection. HIV-infected patients are living longer, and proper attention to the
      management of comorbidities in this population is essential. This article
      summarizes an IAS-USA continuing education webinar presented by Howard Libman,
      MD, in January 2015. 

PMID- 26200711
TI  - Biocontrol evaluation of extracts and a major component, clusianone, from Clusia
      fluminensis Planch. & Triana against Aedes aegypti.
AB  - Studies evaluated the effects of hexanic extracts from the fruits and flowers of
      Clusia fluminensis and the main component of the flower extract, a purified
      benzophenone (clusianone), against Aedes aegypti. The treatment of larvae with
      the crude fruit or flower extracts from C. fluminensis did not affect the
      survival ofAe. aegypti (50 mg/L), however, the flower extracts significantly
      delayed development of Ae. aegypti. In contrast, the clusianone (50 mg/L) isolate
      from the flower extract, representing 54.85% of this sample composition, showed a
      highly significant inhibition of survival, killing 93.3% of the larvae and
      completely blocking development of Ae. aegypti. The results showed, for the first
      time, high activity of clusianone against Ae. aegypti that both killed and
      inhibited mosquito development. Therefore, clusianone has potential for
      development as a biopesticide for controlling insect vectors of tropical
      diseases. Future work will elucidate the mode of action of clusianone isolated
      from C. fluminensis.

PMID- 26200712
TI  - Full-length infectious clone of a low passage dengue virus serotype 2 from
      Brazil.
AB  - Full-length dengue virus (DENV) cDNA clones are an invaluable tool for many
      studies, including those on the development of attenuated or chimeric vaccines
      and on host-virus interactions. Furthermore, the importance of low passage DENV
      infectious clones should be highlighted, as these may harbour critical and unique
      strain-specific viral components from field-circulating isolates. The successful
      construction of a functional Brazilian low passage DENV serotype 2 full-length
      clone through homologous recombination reported here supports the use of a
      strategy that has been shown to be highly useful by our group for the development
      of flavivirus infectious clones and replicons. 

PMID- 26200713
TI  - pTcGW plasmid vectors 1.1 version: a versatile tool for Trypanosoma cruzi gene
      characterisation.
AB  - The functional characterisation of thousands of Trypanosoma cruzi genes remains a
      challenge. Reverse genetics approaches compatible with high-throughput cloning
      strategies can provide the tool needed to tackle this challenge. We previously
      published the pTcGW platform, composed by plasmid vectors carrying different
      options of N-terminal fusion tags based on Gateway(r) technology. Here, we
      present an improved 1.1 version of pTcGW vectors, which is characterised by a
      fully flexible structure allowing an easy customisation of each element of the
      vectors in a single cloning step. Additionally, both N and C-terminal fusions are
      available with new tag options for protein complexes purification. Three of the
      newly created vectors were successfully used to determine the cellular
      localisation of four T. cruzi proteins. The 1.1 version of pTcGW platform can be
      used in a variety of assays, such as protein overexpression, identification of
      protein-protein interaction and protein localisation. This powerful and versatile
      tool allows adding valuable functional information to T. cruzigenes and is freely
      available for scientific community. 

PMID- 26200714
TI  - Cardiovascular dysfunction as a common cause of mortality in hypereosinophilic
      syndromes.

PMID- 26200716
TI  - Better together: Left and right hemisphere engagement to reduce age-related
      memory loss.
AB  - Episodic memory is a cognitive function that appears more susceptible than others
      to the effects of aging. The main aim of this study is to investigate if the
      magnitude of functional hemispheric lateralization during episodic memory test
      was positively correlated with memory performance, proving the presence of a
      beneficial pattern of neural processing in high-performing older adults but not
      in low-performing participants. We have applied anodal transcranial Direct
      Current Stimulation (tDCS) or sham stimulation over left and right hemisphere in
      a group of young subjects and in high-performing and low-performing older
      participants during an experimental verbal episodic memory task. Remarkably,
      young individuals and high-performing older adults exhibited similar performances
      on episodic memory tasks and both groups showed symmetrical recruitment of left
      and right areas during memory retrieval. In contrast, low-performing older
      adults, who obtained lower scores on the memory tasks, demonstrated a greater
      engagement of the left hemisphere during verbal memory task. Furthermore,
      structural equation model was performed for analyzing the interrelations between
      the index of interhemispheric asymmetry and several neuropsychological domains.
      We found that the bilateral engagement of dorsolateral prefrontal cortex and
      parietal cortex regions had a direct correlation with memory and executive
      functions evaluated as latent constructs. These findings drew attention to brain
      maintenance hypothesis. The potential of neurostimulation in cognitive
      enhancement is particularly promising to prevent memory loss during aging. 

PMID- 26200715
TI  - Religious and spiritual interventions in mental health care: a systematic review
      and meta-analysis of randomized controlled clinical trials.
AB  - BACKGROUND: Despite the extensive literature assessing associations between
      religiosity/spirituality and health, few studies have investigated the clinical
      applicability of this evidence. The purpose of this paper was to assess the
      impact of religious/spiritual interventions (RSI) through randomized clinical
      trials (RCTs). METHOD: A systematic review was performed in the following
      databases: PubMed, Scopus, Web of Science, PsycINFO, Cochrane Collaboration,
      Embase and SciELO. Through the use of a Boolean expression, articles were
      included if they: (i) investigated mental health outcomes; (ii) had a design
      consistent with RCTs. We excluded protocols involving intercessory prayer or
      distance healing. The study was conducted in two phases by reading: (1) title and
      abstracts; (2) full papers and assessing their methodological quality. Then, a
      meta-analysis was carried out. RESULTS: Through this method, 4751 papers were
      obtained, of which 23 remained included. The meta-analysis showed significant
      effects of RSI on anxiety general symptoms (p < 0.001) and in subgroups:
      meditation (p < 0.001); psychotherapy (p = 0.02); 1 month of follow-up (p <
      0.001); and comparison groups with interventions (p < 0.001). Two significant
      differences were found in depressive symptoms: between 1 and 6 months and
      comparison groups with interventions (p = 0.05). In general, studies have shown
      that RSI decreased stress, alcoholism and depression. CONCLUSIONS: RCTs on RSI
      showed additional benefits including reduction of clinical symptoms (mainly
      anxiety). The diversity of protocols and outcomes associated with a lack of
      standardization of interventions point to the need for further studies evaluating
      the use of religiosity/spirituality as a complementary treatment in health care.

PMID- 26200717
TI  - The relationship between protein synthesis and protein degradation in object
      recognition memory.
AB  - For decades there has been a consensus that de novo protein synthesis is
      necessary for long-term memory. A second round of protein synthesis has been
      described for both extinction and reconsolidation following an unreinforced test
      session. Recently, it was shown that consolidation and reconsolidation depend not
      only on protein synthesis but also on protein degradation by the ubiquitin
      proteasome system (UPS), a major mechanism responsible for protein turnover.
      However, the involvement of UPS on consolidation and reconsolidation of object
      recognition memory remains unknown. Here we investigate in the CA1 region of the
      dorsal hippocampus the involvement of UPS-mediated protein degradation in
      consolidation and reconsolidation of object recognition memory. Animals with
      infusion cannulae stereotaxically implanted in the CA1 region of the dorsal
      hippocampus, were exposed to an object recognition task. The UPS inhibitor beta
      Lactacystin did not affect the consolidation and the reconsolidation of object
      recognition memory at doses known to affect other forms of memory (inhibitory
      avoidance, spatial learning in a water maze) while the protein synthesis
      inhibitor anisomycin impaired the consolidation and the reconsolidation of the
      object recognition memory. However, beta-Lactacystin was able to reverse the
      impairment caused by anisomycin on the reconsolidation process in the CA1 region
      of the hippocampus. Therefore, it is possible to postulate a direct link between
      protein degradation and protein synthesis during the reconsolidation of the
      object recognition memory. 

PMID- 26200718
TI  - The neuroergonomic evaluation of human machine interface design in air traffic
      control using behavioral and EGG/ERP measures.
AB  - The Air Traffic Control (ATC) environment is complex and safety-critical. Whilst
      exchanging information with pilots, controllers must also be alert to visual
      notifications displayed on the radar screen (e.g., warning which indicates a loss
      of minimum separation between aircraft). Under the assumption that attentional
      resources are shared between vision and hearing, the visual interface design may
      also impact the ability to process these auditory stimuli. Using a simulated ATC
      task, we compared the behavioral and neural responses to two different visual
      notification designs--the operational alarm that involves blinking colored "ALRT"
      displayed around the label of the notified plane ("Color-Blink"), and the more
      salient alarm involving the same blinking text plus four moving yellow chevrons
      ("Box-Animation"). Participants performed a concurrent auditory task with the
      requirement to react to rare pitch tones. P300 from the occurrence of the tones
      was taken as an indicator of remaining attentional resources. Participants who
      were presented with the more salient visual design showed better accuracy than
      the group with the suboptimal operational design. On a physiological level,
      auditory P300 amplitude in the former group was greater than that observed in the
      latter group. One potential explanation is that the enhanced visual design freed
      up attentional resources which, in turn, improved the cerebral processing of the
      auditory stimuli. These results suggest that P300 amplitude can be used as a
      valid estimation of the efficiency of interface designs, and of cognitive load
      more generally.

PMID- 26200720
TI  - Ultrasonography as a Guiding Method in Breast Micro-Calcification Vacuum-Assisted
      Biopsies.
AB  - Purpose: To assess the visibility of breast micro-calcifications using
      ultrasonography (US) and the accuracy and clinical usefulness of vacuum-assisted
      biopsy (VAB) using US guidance (USVAB) as compared to stereotactic guidance
      (SVAB). Materials and Methods: The study material comprised 158 retrospectively
      reviewed micro-calcification cases examined with US before VAB. The pre-biopsy US
      positivity frequency distributions were calculated, and the sensitivity,
      specificity and accuracy of VAB determined by comparing VAB histology with the
      surgical pathology or a 12-month follow-up. Results: 158 US examinations yielded
      80 positive and 78 negative results. US positivity correlated to a large size and
      a suspicious BI-RADS category of the calcifications. USVAB was performed in 49
      cases with 61 % malignant, 12 % high-risk and 27 % benign results. The
      percentages for the 109 SVAB cases were 40 %, 28 % and 32 %, respectively.
      Specimen radiography demonstrated calcifications in 48 of the 49 (98 %) USVAB
      cases and in 107 of the 109 (98 %) SVAB cases. The overall accuracy of VAB was 94
      % (USVAB 98 %, SVAB 94 %), the sensitivity was 88 % (USVAB 97 %, SVAB 83 %), and
      the specificity was 100 %. The higher sensitivity of USVAB was due to an
      accumulation of atypical hyperplasia diagnoses in the SVAB group. The final
      diagnosis was invasive ductal carcinoma in 21 US-positive and in 4 US-negative
      cases. Conclusion: Approximately 50 % of mammographically detected micro
      calcifications could be detected with ultrasonography. US was found to be a
      valuable alternative guidance method for vacuum-assisted biopsy of micro
      calcifications with a technical success rate and diagnostic accuracy well
      comparable to the stereotactic method.

PMID- 26200719
TI  - Molecular Characterization and Biochemical and Histopathological Aspects of the
      Parasitism of Haemoproteus spp. in Southern Caracaras (Caracara plancus).
AB  - Haemoproteid species have a wide global distribution, and they have been
      described in falcon species in several parts of the world. However, few studies
      in South America have focused on these birds. Haemoproteus spp. infections have
      been reported as the causative agents of serious histopathological changes, which
      can lead to the death of the host. Thus, this study aimed to molecularly and
      phylogenetically characterize Haemoproteus spp. in Caracara plancus, to
      characterize aspects of parasitism through clinical analysis and biochemical
      parameters, and to describe the histopathology of infection. To examine these
      aspects, 5 southern caracaras were examined clinically, and blood samples were
      collected. Blood smears were subsequently utilized in parasitemia calculations,
      PCR amplification, and serum biochemical investigations. Histological sections of
      the liver, kidneys, spleen, and heart were examined to check for possible
      histopathological changes. The birds showed clinical signs such as pallor and
      prostration that are consistent with Haemoproteus spp. infection. Moreover, the
      examination of the blood smears revealed 0.07% parasitemia in young gametocytes
      only. The PCR and sequencing results confirmed that the parasites belonged to
      Haemoproteus spp. The activity of aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) enzymes, albumin, total serum proteins, and enzymatic urea
      were first described in C. plancus and serve as reference for future studies of
      bird species parasitized by Haemoproteus spp. Histopathology results showed signs
      of injury that were consistent with haemosporidian infection in the tissues of
      the analyzed organs. The present study is preliminary, and additional studies of
      Haemoproteus spp. infections in other bird species are needed to better
      understand the relationship between parasites and hosts, because despite the low
      parasitemia recorded, biochemical and histopathological changes in various organs
      were observed. 

PMID- 26200722
TI  - Pharmacological Treatments for Acute Respiratory Distress Syndrome.

PMID- 26200721
TI  - HIV and new onset seizures: slipping through the cracks in HIV care and
      treatment.
AB  - OBJECTIVES: The aim of the study was to describe patient characteristics and
      outcomes among HIV-positive adults presenting to a Zambian tertiary care hospital
      with new-onset seizures. METHODS: From July 2011 to June 2013, adults with
      seizures and a known or probable diagnosis of HIV infection were screened for a
      cohort study. Demographic and clinical data were obtained, including information
      on engagement in HIV services and in-patient mortality. Analyses were conducted
      to identify characteristics associated with poor engagement in care and death.
      RESULTS: A total of 320 of 351 screened adults were HIV-positive, with 268 of 320
      experiencing new-onset seizures. Of these, 114 of 268 (42.5%) were female, and
      their mean age was 36.8 years. Seventy-nine of the 268 patients (29.5%) were
      diagnosed with HIV infection during the index illness. Among those who were aware
      of their HIV-positive status, 59 of 156 (37.8%) had disengaged from care.
      Significant functional impairment (Karnofsky score < 50) was evident in 44.0% of
      patients. Cerebrospinal fluid was not obtained in 108 of 268 (40.3%). In-patient
      mortality outcomes were available for 214 patients, and 47 of these 214 (22.0%)
      died during hospitalization. Patients with significant functional impairment were
      more likely to undergo lumbar puncture (P = 0.046). Women and the functionally
      impaired were more likely to die (P = 0.04 and < 0.001, respectively).
      CONCLUSIONS: Despite the availability of care, less than half of HIV-infected
      people with new-onset seizures were actively engaged in care and in-patient
      mortality rates were high. In the absence of clinical contraindication, lumbar
      puncture should be performed to diagnose treatable conditions and reduce
      morbidity and mortality. Continued efforts are needed to expand community-based
      testing and improve HIV care retention rates. Qualitative studies are needed to
      elucidate factors contributing to lumbar puncture usage in this population.

PMID- 26200724
TI  - Can Health Care Survive Current Electronic Health Record Usability?

PMID- 26200725
TI  - Postgraduate Fellowships: What Is in It for New Acute Care Nurse Practitioners?

PMID- 26200726
TI  - The Nurse Leader's Role in Supporting Healthy Work Environments.

PMID- 26200727
TI  - Redesigning Orientation in an Intensive Care Unit Using 2 Theoretical Models.
AB  - BACKGROUND: To accommodate a higher demand for critical care nurses, an
      orientation program in a surgical intensive care unit was revised and
      streamlined. Two theoretical models served as a foundation for the revision and
      resulted in clear clinical benchmarks for orientation progress evaluation.
      PURPOSE: The purpose of the project was to integrate theoretical frameworks into
      practice to improve the unit orientation program. METHODS: Performance
      improvement methods served as a framework for the revision, and outcomes were
      measured before and after implementation. RESULTS: The revised orientation
      program increased 1- and 2-year nurse retention and decreased turnover. Critical
      care knowledge increased after orientation for both the preintervention and
      postintervention groups. CONCLUSION: Incorporating a theoretical basis for
      orientation has been shown to be successful in increasing the number of nurses
      completing orientation and improving retention, turnover rates, and knowledge
      gained.

PMID- 26200728
TI  - Feeding Protocols for Neonates With Hypoplastic Left Heart Syndrome: A Review.
AB  - Optimizing nutrition in neonates with hypoplastic left heart syndrome is
      essential, given the high rate of growth failure in this population. Infants with
      hypoplastic left heart syndrome are predisposed to nutritional deficiency as a
      result of their increased metabolic demand; however, early enteral feeding also
      increases the risk of serious gastrointestinal morbidity and mortality caused by
      poor intestinal perfusion. Consequently, providers have difficulty deciding when
      and how to safely feed these patients. A review of the literature found that
      implementation of a structured enteral feeding protocol may decrease the risk of
      gastrointestinal complications while also minimizing dependence on parenteral
      nutrition and decreasing length of hospital stay. As these studies were limited,
      further research is warranted to establish a best practice feeding protocol to
      decrease risk and optimize nutrition in this fragile population. 

PMID- 26200729
TI  - Introduction to Infectious Disease Symposium.

PMID- 26200730
TI  - Antimicrobial Resistance: Thinking Outside the Box.
AB  - The health care system is challenged by another serious issue: antimicrobial
      resistance. Clostridium difficile is the most common infection in health care
      institutions and is becoming resistant to standard treatment. Carbapenem
      resistant enterobacteriaceae can be found in almost every state in the United
      States. Confounding the antimicrobial resistance issue is the fact that few new
      antimicrobials are being developed by pharmaceutical companies. The situation is
      so critical that the White House issued a strategic plan in September 2014 to
      deal with antimicrobial resistance. One challenge in that plan is to better
      understand how microbes have become resistant. Microbes have developed defense
      mechanisms such as bacteriophages and bacteriocins to survive for thousands of
      years. If science can start to use these mechanisms to help combat resistant
      organisms in combination with antimicrobials and strong epidemiological
      interventions, the battle against antimicrobial resistance may succeed. 

PMID- 26200732
TI  - Intravenous Antibiotics Used in the Treatment of Methicillin-Resistant
      Staphylococcus Aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) continues to cause significant
      morbidity and mortality. Despite advances in medical care, the prevalence of both
      community-acquired and hospital-acquired MRSA has progressively increased.
      Community-acquired MRSA typically occurs in patients without recent illness or
      hospitalization, presents as acute skin and soft tissue infections, and is
      usually not multidrug resistant. Hospital-acquired MRSA, however, presents in
      patients recently hospitalized or treated in long-term care settings and in those
      who have had medical procedures and is usually associated with multidrug
      resistant strains. Both types of infections, if not properly treated, have the
      potential to become invasive. This article discusses current intravenous
      antibiotics that are available for the empiric treatment of MRSA infections along
      with a newer phenomenon known as the "seesaw effect." 

PMID- 26200733
TI  - Antibiotic Dosing in Critically Ill Patients Undergoing Renal Replacement
      Therapy.
AB  - Continuous renal replacement therapy is frequently used to manage acute renal
      failure in critically ill patients. Antibiotic drugs used to treat infections in
      critically ill patients need to be dosed on the basis of the method of renal
      replacement therapy to be used, degree of residual renal function, and the
      sensitivity of the organism to be treated. Antibiotic dosing regimens must then
      be continuously monitored and adjusted according to modifications made to the
      renal replacement circuit and the patient's underlying condition.

PMID- 26200734
TI  - Challenges in Hospital-Associated Infection Management: A Unit Perspective.
AB  - Maintaining a successful unit-based continuous quality improvement program for
      managing hospital-associated infections is a huge challenge and an overwhelming
      task. It requires strong organizational support and unit leadership, human and
      fiscal resources, time, and a dedicated and motivated nursing staff. A great deal
      of effort goes into implementing, monitoring, reporting, and evaluating quality
      improvement initiatives and can lead to significant frustration on the part of
      the leadership team and nursing staff when quality improvement efforts fail to
      produce the desired results. Each initiative presents its own unique set of
      challenges; however, common issues influence all initiatives. These common issues
      include organization and unit culture, current clinical practice guidelines being
      used to drive the initiatives, performance discrepancies on the part of nursing
      staff, availability of resources including equipment and supplies, monitoring of
      the data, and conflicting quality improvement priorities. 

PMID- 26200735
TI  - Ebola at the National Institutes of Health: Perspectives From Critical Care
      Nurses.
AB  - Infectious disease events were in the headlines in 2014. West Africa experienced
      the worst Ebola virus disease (EVD) outbreak ever recorded. The world was stunned
      when the deadly virus began to spread to other countries. The health care system
      in the United States responded by designating specialized centers to care for
      patients with EVD. All health care workers must understand the isolation
      processes involved in caring for these patients. Using personal protective
      equipment is imperative and requires adjustments in how care is provided.
      Staffing patterns must be altered to provide safe care, while maintaining safety
      of health care workers. This article provides perspectives of the critical care
      nurse manager and bedside nurse who participated in the development of the care
      processes for patients with EVD at the National Institutes of Health to help
      health care colleagues better understand issues experienced and to help prepare
      them if they encounter patients with EVD. 

PMID- 26200736
TI  - Blending Quality Improvement and Research Methods for Implementation Science,
      Part I: Design and Data Collection.

PMID- 26200737
TI  - Temporary Pacing After Cardiac Surgery.

PMID- 26200738
TI  - Molecular Characterization of the Human Immunodeficiency Virus Type 1 in Women
      and Their Vertically Infected Children.
AB  - Approximately 35 million people worldwide are infected with human
      immunodeficiency virus (HIV) around 3.2 million of whom are children under 15
      years. Mother-to-child-transmission (MTCT) of HIV-1 accounts for 90% of all
      infections in children. Despite great advances in the prevention of MTCT in
      Brazil, children are still becoming infected. Samples from 19 HIV-1-infected
      families were collected. DNA was extracted and fragments from gag, pol, and env
      were amplified and sequenced directly. Phylogenetic reconstruction was performed.
      Drug resistance analyses were performed in pol and env sequences. We found 82.1%
      of subtype B and 17.9% of BF recombinants. A prevalence of 43.9% drug resistance
      associated mutations in pol sequences was identified. Of the drug-naive children
      33.3% presented at least one mutation related to protease inhibitor/nucleoside
      reverse transcriptase inhibitor/nonnucleoside reverse transcriptase inhibitor
      (PI/NRTI/NNRTI) resistance. The prevalence of transmitted drug resistance
      mutations was 4.9%. On env we found a low prevalence of HR1 (4.9%) and HR2
      (14.6%) mutations.

PMID- 26200739
TI  - Disassortative mating prevails in style-dimorphic Narcissus papyraceus despite
      low reciprocity and compatibility of morphs.
AB  - Evolution to reduce inbreeding can favor disassortative (intermorph) over
      assortative (intramorph) mating in hermaphroditic sexually polymorphic plant
      species. Heterostyly enhances disassortative pollination through reciprocal
      placement of stigmas and anthers of morphs and appropriate pollinators. Stylar
      dimorphism in which there is not reciprocal anther placement may compromise
      disassortative mating, particularly when there is not intramorph incompatibility.
      Variable rates of disassortative mating along with differential female fecundity
      or siring success among floral morphs could lead to variation in morph ratio. We
      investigated mating patterns, female fecundity, and siring success of style
      length morphs in Narcissus papyraceus, a self-incompatible but morph-compatible
      species with dimorphic (long- and short-styled) and monomorphic (long-styled)
      populations in central and north regions of its range, respectively. We
      established experimental populations in both regions and exposed them to ambient
      pollinators. Using paternity analysis, we found similar siring success of morphs
      and high disassortative mating in most populations. Female fecundity of morphs
      was similar in all populations. Although these results could not completely
      explain the loss of dimorphism in the species' northern range, they provided
      evidence for the evolutionary stability of stylar dimorphism in N. papyraceus in
      at least some populations. Our findings support the hypothesis that prevailing
      intermorph mating is key for the maintenance of stylar dimorphism. 

PMID- 26200740
TI  - Designing Hydrophobically Modified Polysaccharide Derivatives for Highly
      Efficient Enzyme Immobilization.
AB  - In this contribution, a hydrophobically modified polysaccharide derivative is
      synthesized in an eco-friendly solvent water by conjugation of benzylamine with
      the backbone of the biopolymer. Owing to the presence of aromatic moieties, the
      resulting water-soluble polysaccharide derivative self-assembles spontaneously
      and selectively from solution on the surface of nanometric thin films and sheets
      of polystyrene (PS). The synthetic polymer modified in this way bears a
      biocompatible nanolayer suitable for the immobilization of horseradish peroxidase
      (HRP), a heme-containing metalloenzyme often employed in biocatalysis and
      biosensors. Besides the detailed characterization of the polysaccharide
      derivative, a quartz crystal microbalance with dissipation (QCM-D) and atomic
      force microscopy (AFM) are used to investigate the binding efficiency and
      interaction of HRP with the tailored polysaccharide interfaces. Subsequent enzyme
      activity tests reveal details of the interaction of HRP with the solid support.
      The novel polysaccharide derivative and its use as a material for the selective
      modification of PS lead to a beneficial, hydrophilic environment for HRP,
      resulting in high enzymatic activities and a stable immobilization of the enzyme
      for biocatalytic and analytic purposes. 

PMID- 26200741
TI  - Structure-Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist
      (2S,3R)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid.
AB  - Herein we describe the first structure-activity relationship study of the broad
      range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid
      (1) by exploring the pharmacological effect of substituents in the 4, 4', or 5'
      positions and the bioisosteric substitution of the distal carboxylic acid for a
      phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4'
      position 2a which induced a preference in binding affinity for homomeric GluK3
      over GluK1 (Ki = 0.87 and 4.8 MUM, respectively). Two X-ray structures of ligand
      binding domains were obtained: 2e in GluA2-LBD and 2f in GluK1-LBD, both at 1.9 A
      resolution. Compound 2e induces a D1-D2 domain opening in GluA2-LBD of 17.3-18.8
      degrees  and 2f a domain opening in GluK1-LBD of 17.0-17.5 degrees  relative to
      the structures with glutamate. The pyrrolidine-2-carboxylate moiety of 2e and 2f
      shows a similar binding mode as kainate. The 3-carboxyphenyl ring of 2e and 2f
      forms contacts comparable to those of the distal carboxylate in kainate. 

PMID- 26200742
TI  - Reproducibility and Agreement Between 2 Spectral Domain Optical Coherence
      Tomography Devices for Anterior Chamber Angle Measurements.
AB  - PURPOSE: To compare anterior chamber angle parameters based on the location of
      Schwalbe line (SL) from 2 spectral domain optical coherence tomography (SD-OCT)
      instruments and to measure their reproducibility. METHODS: Forty-two eyes from 21
      normal, healthy participants underwent imaging of the inferior irido-corneal
      angle with the Spectralis and Cirrus SD-OCT under tightly controlled low-light
      conditions. SL-angle opening distance (SL-AOD) and SL-trabecular iris space area
      (SL-TISA) were measured by masked, certified graders at the Doheny Imaging
      Reading Center using customized grading software. Interinstrument and
      intrainstrument, as well as interobserver and intraobserver reproducibility of SL
      AOD and SL-TISA measurements were evaluated by intraclass correlation
      coefficients (ICCs) and Bland-Altman plots with limits of agreement (LoA).
      RESULTS: The mean SL-AOD was 0.662+/-0.191 mm in Spectralis and 0.677+/-0.213 mm
      in Cirrus. The mean SL-TISA was 0.250+/-0.073 mm in Spectralis and 0.256+/-0.082
      mm in Cirrus. The agreement for intrainstrument (ICCs>0.979), intragrader
      (ICCs>0.992), and intergrader (ICCs>0.929) was excellent. Excellent agreement
      between the 2 devices was also documented with a mean difference of -0.016 (LoA 
      0.125 to 0.092) mm for SL-AOD and -0.007 (LoA -0.056 to 0.043) mm in SL-TISA.
      CONCLUSIONS: Both SD-OCTs provided comparable measurements and permitted
      calculation of SL-based angle metrics. There was excellent interinstrument and
      intrainstrument and intraobserver and interobserver reproducibility for
      Spectralis and Cirrus SD-OCTs, suggesting true interchangeability between SD-OCT
      devices. This has the potential to lead to development of standardized grading
      assessments and quantification of angle parameters that would be valid across
      various SD-OCT devices.

PMID- 26200743
TI  - Diagnostic Power of Macular Retinal Thickness Analysis and Structure-Function
      Relationship in Glaucoma Diagnosis Using SPECTRALIS OCT.
AB  - AIMS: To evaluate the diagnostic power of the Posterior Pole Asymmetry Analysis
      (PPAA) from the SPECTRALIS OCT in glaucoma diagnosis and to define the
      correlation between the visual field sensitivity (VFS) and macular retinal
      thickness (MRT). METHODS: 90 consecutive open-angle glaucoma patients and 23
      healthy subjects were enrolled. All subjects underwent Visual Field test
      (Humphrey Field Analyzer, central 24-2 SITA-Standard) and SD-OCT volume scans
      (SPECTRALIS, Posterior Pole Asymmetry Analysis). The areas under the Receiving
      Operating Characteristic curve (AROC) were calculated to assess discriminating
      power for glaucoma, at first considering total MRT values and hemisphere MRT
      value and then quadrant MRT values from 16 square cells in a 8 x 8 posterior pole
      retinal thickness map that were averaged for a mean retinal thickness value.
      Structure function correlation was performed for total values, hemisphere values
      and for each quadrant compared to the matching central test points of the VF.
      RESULTS: The AROCs ranged from 0.70 to 0.82 (p < 0.0001), with no significant
      differences between each other. The highest AROC observed was in inferior nasal
      quadrant. The VFS showed a strong correlation only with the corresponding MRT
      value s for quadrant analysis: Superior Temporal (r = 0.33, p = 0.0013), Superior
      Nasal (r = 0.43, p < 0.0001), Inferior Temporal (r = 0.57, p < 0.0001) and
      Inferior Nasal (r = 0.55, p < 0.0001). CONCLUSION: the quadrant analysis showed
      statistically significant structure-function correlations and may provide
      additional data for the diagnostic performance of SPECTRALIS OCT.

PMID- 26200745
TI  - The use of in situ near infrared imaging and Raman mapping to study the
      disproportionation of a drug HCl salt during dissolution.
AB  - NIR imaging and Raman mapping of the dissolution of model pharmaceutical
      formulations containing the HCl salt of a developmental compound, were carried
      out using a custom designed flow through cell. The results of this work have
      shown that NIR imaging and Raman mapping are capable of monitoring the
      distribution of the components in a formulation during dissolution while also
      revealing any form changes which may occur in real time. The NIR and Raman data
      revealed that the drug underwent conversion to the free base when water was used
      as the dissolution medium. However, in 0.1M HCl this conversion was no longer
      seen as the medium was below the pHmax (the pH of saturation of both unionised
      and ionised species and above which the free base can form) of the drug. The data
      from both approaches broadly agreed demonstrating the applicability of these
      methods to studying and enhancing our understanding of the complex physical and
      chemical processes which occur during dissolution in real time. 

PMID- 26200744
TI  - Compliance With Evidence-Based Guidelines and Interhospital Variation in
      Mortality for Patients With Severe Traumatic Brain Injury.
AB  - IMPORTANCE: Compliance with evidence-based guidelines in traumatic brain injury
      (TBI) has been proposed as a marker of hospital quality. However, the association
      between hospital-level compliance rates and risk-adjusted clinical outcomes for
      patients with TBI remains poorly understood. OBJECTIVE: To examine whether
      hospital-level compliance with the Brain Trauma Foundation guidelines for
      intracranial pressure monitoring and craniotomy is associated with risk-adjusted
      mortality rates for patients with severe TBI. DESIGN, SETTING, AND PARTICIPANTS:
      All adult patients (N = 734) who presented to a regional consortium of 14
      hospitals from January 1, 2009, through December 31, 2010, with severe TBI (ie,
      blunt head trauma, Glasgow Coma Scale score of <9, and abnormal intracranial
      findings from computed tomography of the head). Data analysis took place from
      December 2013 through January 2015. We used hierarchical mixed-effects models to
      assess the association between hospital-level compliance with Brain Trauma
      Foundation guidelines and mortality rates after adjusting for patient-level
      demographics, severity of trauma (eg, mechanism of injury and Injury Severity
      Score), and TBI-specific variables (eg, cranial nerve reflexes and findings from
      computed tomography of the head). MAIN OUTCOMES AND MEASURES: Hospital-level risk
      adjusted inpatient mortality rate and hospital-level compliance with Brain Trauma
      Foundation guidelines for intracranial pressure monitoring and craniotomy.
      RESULTS: Unadjusted mortality rates varied by site from 20.0% to 50.0% (median,
      42.6; interquartile range, 35.5-46.2); risk-adjusted rates varied from 24.3% to
      56.7% (median, 41.1; interquartile range, 36.4-47.8). Overall, only 338 of 734
      patients (46.1%) with an appropriate indication underwent placement of an
      intracranial pressure monitor and only 134 of 335 (45.6%) underwent craniotomy.
      Hospital-level compliance ranged from 9.6% to 65.2% for intracranial pressure
      monitoring and 6.7% to 76.2% for craniotomy. Despite widespread variation in
      compliance across hospitals, we found no association between hospital-level
      compliance rates and risk-adjusted patient outcomes (Spearman rho = 0.030 [P =
      .92] for ICP monitoring and Spearman rho = -0.066 [P = .83] for craniotomy).
      CONCLUSIONS AND RELEVANCE: Hospital-level compliance with evidence-based
      guidelines has minimal association with risk-adjusted outcomes in patients with
      severe TBI. Our results suggest that caution should be taken before using
      compliance with these measures as independent quality metrics. Given the
      complexity of TBI care, outcomes-based metrics, including functional recovery,
      may be more accurate than current process measures at determining hospital
      quality.

PMID- 26200746
TI  - Investigating the effect of tablet thickness and punch curvature on density
      distribution using finite elements method.
AB  - Finite elements method was used to study the influence of tablet thickness and
      punch curvature on the density distribution inside convex faced (CF) tablets. The
      modeling of the process was conducted on 2 pharmaceutical excipients (anhydrous
      calcium phosphate and microcrystalline cellulose) by using Drucker-Prager Cap
      model in Abaqus((r)) software. The parameters of the model were obtained from
      experimental tests. Several punch shapes based on industrial standards were used.
      A flat-faced (FF) punch and 3 convex faced (CF) punches (8R11, 8R8 and 8R6) with
      a diameter of 8mm were chosen. Different tablet thicknesses were studied at a
      constant compression force. The simulation of the compaction of CF tablets with
      increasing thicknesses showed an important change on the density distribution
      inside the tablet. For smaller thicknesses, low density zones are located toward
      the center. The density is not uniform inside CF tablets and the center of the 2
      faces appears with low density whereas the distribution inside FF tablets is
      almost independent of the tablet thickness. These results showed that FF and CF
      tablets, even obtained at the same compression force, do not have the same
      density at the center of the compact. As a consequence differences in tensile
      strength, as measured by diametral compression, are expected. This was confirmed
      by experimental tests. 

PMID- 26200747
TI  - In-line non-invasive turbidimetry as a tool to ensure content uniformity in the
      betamethasone filling process.
AB  - The filling process of liquid suspensions is a difficult operation,mainly due to
      drug settling. Small variations during the process may lead to serious deviations
      in the API content uniformity of the finished product, particularly if the drug
      settles fast. Real-time non-invasive monitoring of liquid suspensions is a useful
      approach to ensure an acceptable API content in the finished product. The aim of
      this study was to develop a method based on non-invasive turbidity measurements
      for in-line determinations of betamethasone content uniformity during the filling
      process of injections. Owing to the constructive features of the developed
      system, the determinations were performed in a non-destructive and non-invasive
      way, thus allowing the analysis of the whole batch and minimizing the risk of
      contaminating the product. The results obtained by the method proposed in this
      study demonstrated that non-invasive turbidimetry is a powerful tool for
      continuous monitoring of the filling process of betamethasone injections, within
      the Quality by Design framework (FDA, 2009). 

PMID- 26200748
TI  - Cellular uptake, cytotoxicity and in-vivo evaluation of Tamoxifen citrate loaded
      niosomes.
AB  - One of the main challenges in Tamoxifen cancer therapy is achieving localized,
      efficient and sustained delivery without harming normal healthy organs. This
      study focused on evaluating Tamoxifen Citrate (TMC) niosomes for localized cancer
      therapy through in-vitro breast cancer cytotoxicity as well as in-vivo solid anti
      tumor efficacy. Different niosomal formulae were prepared by film hydration
      technique and characterized for entrapment efficiency% (E. E), vesicle size,
      morphology, and in-vitro release. The cellular uptake and anti-cancer activity
      were also tested in-vitro using MCF-7 breast cancer cell line. Moreover, in-vivo
      anti-tumor efficacy was examined in Ehrlich carcinoma mice model through
      reporting solid tumor volume regression and tissue TMC distribution. The obtained
      niosomes prepared with Span 60: cholesterol (1: 1 molar ratio) showed a distinct
      nano-spherical shape with EE up to 92.3%+/- 2.3. Remarkably prolonged release of
      TMC following diffusion release behavior was detected. The optimized formula
      showed significantly enhanced cellular uptake (2.8 fold) and exhibited
      significantly greater cytotoxic activity with MCF-7 breast cancer cell line. In
      vivo experiment showed enhanced tumor volume reduction of niosomal TMC when
      compared to free TMC. Based on these results, the prepared niosomes demonstrated
      to be promising as a nano-size delivery vehicle for localized and sustained TMC
      cancer therapy.

PMID- 26200749
TI  - Use of anodized titanium alloy as drug carrier: Ibuprofen as model of drug
      releasing.
AB  - The use of osteoarticular implants has improved the quality of life of millions
      of patients. In this work nanotubular structures tailored made on Ti6Al4V
      substrates was used as drug delivery system of ibuprofen as a proof of concept.
      Three different nanotubular films with different sizes and forms (NT, NT+ and
      NTb) were analysed. Samples were soaked in a solution of 660 mg ibuprofen/20 mL n
      pentane. The ibuprofen release in aqueous medium was evaluated by liquid
      chromatography reversed-phase (RP-HPLC). To calculate the observed constant k,
      the amount of ibuprofen released was plotted versus the time using linear
      regression according to the zero-order, first-order, second-order and Higuchi
      model. The release of ibuprofen was constant and independent of the
      concentration. The kinetic constant obtained was 0.021 (NT), 0.022 (NT+) and
      0.013 (NTb) being the correlation factor of 0.98 (zero-order) where the maximum
      correlation factor was reached. These results indicate that the delivery process
      from NT and NT+ is similar and slower that NTb. In all the cases was inside the
      therapeutically range. These results showed the potential of these modifications
      in order to develop implants that can carry different molecules of medical
      importance.

PMID- 26200750
TI  - Application of spherical silicate to prepare solid dispersion dosage forms with
      aqueous polymers.
AB  - The objective of this study is to prepare and characterize solid dispersions of
      nifedipine (NP) using porous spherical silicate micro beads (MB) that were
      approximately 100 MUm in diameter with vinylpyrrolidone/vinyl acetate copolymer
      (PVP/VA) and a Wurster-type fluidized bed granulator. Compared with previously
      reported solid dispersion using only MB, the supersaturation of NP dissolved from
      the proposed system of MB and PVP/VA was maintained during dissolution tests. The
      proposed system produced a solid dispersion product coated on MB, and morphology
      was maintained after the coating process to prepare solid dispersion; therefore,
      the powder characteristics, such as flowability of the proposed solid dispersion
      product, was tremendously preferable to that of the conventional spray-dried
      solid dispersions of NP with PVP/VA, expecting to make the consequent
      manufacturing processes easy for development. Another advantage in the terms of
      manufacturing is its simple process to prepare solid dispersion by spraying the
      drug and polymer that were dissolved in an organic solvent onto a MB in a Wurster
      type fluidized bed granulator, thus, simplifying the optimization and scale-up
      with ease.

PMID- 26200751
TI  - Delivery of retinoic acid to LNCap human prostate cancer cells using solid lipid
      nanoparticles.
AB  - In this study retinoic acid (RTA) loaded solid lipid nanoparticles (SLNs) were
      optimized by tuning the process parameters (pressure/temperature) and using
      different lipids to develop nanodispersions with enhanced anticancer activity.
      The RTA-SLN dispersions were produced by high-pressure homogenization and
      characterized in terms of particle size, zeta potential, drug entrapment
      efficiency, stability, transmission electron microscopy (TEM), atomic force
      microscopy (AFM), X-ray diffraction (XRD) and in vitro drug release. Thermal and
      X-ray analysis showed the RTA to be in the amorphous state, whilst microscopic
      images revealed a spherical shape and uniform particle size distribution of the
      nanoparticles. Anticancer efficiency was evaluated by incubating RTA-SLNs with
      human prostate cancer (LNCap) cells, which demonstrated reduced cell viability
      with increased drug concentrations (9.53% at 200 ug/ml) while blank SLNs
      displayed negligible cytotoxicity. The cellular uptake of SLN showed localization
      within the cytoplasm of cells and flow cytometry analysis indicated an increase
      in the fraction of cells expressing early apoptotic markers, suggesting that the
      RTA loaded SLNs are able to induce apoptosis in LNCap cells. The RTA-SLN
      dispersions have the potential to be used for prostate anticancer treatment.

PMID- 26200752
TI  - Construction of biological networks from unstructured information based on a semi
      automated curation workflow.
AB  - Capture and representation of scientific knowledge in a structured format are
      essential to improve the understanding of biological mechanisms involved in
      complex diseases. Biological knowledge and knowledge about standardized
      terminologies are difficult to capture from literature in a usable form. A semi
      automated knowledge extraction workflow is presented that was developed to allow
      users to extract causal and correlative relationships from scientific literature
      and to transcribe them into the computable and human readable Biological
      Expression Language (BEL). The workflow combines state-of-the-art linguistic
      tools for recognition of various entities and extraction of knowledge from
      literature sources. Unlike most other approaches, the workflow outputs the
      results to a curation interface for manual curation and converts them into BEL
      documents that can be compiled to form biological networks. We developed a new
      semi-automated knowledge extraction workflow that was designed to capture and
      organize scientific knowledge and reduce the required curation skills and effort
      for this task. The workflow was used to build a network that represents the
      cellular and molecular mechanisms implicated in atherosclerotic plaque
      destabilization in an apolipoprotein-E-deficient (ApoE(-/-)) mouse model. The
      network was generated using knowledge extracted from the primary literature. The
      resultant atherosclerotic plaque destabilization network contains 304 nodes and
      743 edges supported by 33 PubMed referenced articles. A comparison between the
      semi-automated and conventional curation processes showed similar results, but
      significantly reduced curation effort for the semi-automated process. Creating
      structured knowledge from unstructured text is an important step for the
      mechanistic interpretation and reusability of knowledge. Our new semi-automated
      knowledge extraction workflow reduced the curation skills and effort required to
      capture and organize scientific knowledge. The atherosclerotic plaque
      destabilization network that was generated is a causal network model for vascular
      disease demonstrating the usefulness of the workflow for knowledge extraction and
      construction of mechanistically meaningful biological networks. 

PMID- 26200753
TI  - Pre_GI: a global map of ontological links between horizontally transferred
      genomic islands in bacterial and archaeal genomes.
AB  - The Predicted Genomic Islands database (Pre_GI) is a comprehensive repository of
      prokaryotic genomic islands (islands, GIs) freely accessible at
      http://pregi.bi.up.ac.za/index.php. Pre_GI, Version 2015, catalogues 26 744
      islands identified in 2407 bacterial/archaeal chromosomes and plasmids. It
      provides an easy-to-use interface which allows users the ability to query against
      the database with a variety of fields, parameters and associations. Pre_GI is
      constructed to be a web-resource for the analysis of ontological roads between
      islands and cartographic analysis of the global fluxes of mobile genetic elements
      through bacterial and archaeal taxonomic borders. Comparison of newly identified
      islands against Pre_GI presents an alternative avenue to identify their ontology,
      origin and relative time of acquisition. Pre_GI aims to aid research on
      horizontal transfer events and materials through providing data and tools for
      holistic investigation of migration of genes through ecological niches and
      taxonomic boundaries.

PMID- 26200754
TI  - G4RNA: an RNA G-quadruplex database.
AB  - G-quadruplexes (G4) are tetrahelical structures formed from planar arrangement of
      guanines in nucleic acids. A simple, regular motif was originally proposed to
      describe G4-forming sequences. More recently, however, formation of G4 was
      discovered to depend, at least in part, on the contextual backdrop of neighboring
      sequences. Prediction of G4 folding is thus becoming more challenging as G4
      outlier structures, not described by the originally proposed motif, are
      increasingly reported. Recent observations thus call for a comprehensive tool,
      capable of consolidating the expanding information on tested G4s, in order to
      conduct systematic comparative analyses of G4-promoting sequences. The G4RNA
      Database we propose was designed to help meet the need for easily-retrievable
      data on known RNA G4s. A user-friendly, flexible query system allows for data
      retrieval on experimentally tested sequences, from many separate genes, to assess
      G4-folding potential. Query output sorts data according to sequence position, G4
      likelihood, experimental outcomes and associated bibliographical references.
      G4RNA also provides an ideal foundation to collect and store additional sequence
      and experimental data, considering the growing interest G4s currently generate.

PMID- 26200755
TI  - First-Trimester Use of Selective Serotonin-Reuptake Inhibitors and the Risk of
      Birth Defects.

PMID- 26200756
TI  - Synthesis of Catecholate Ligands with Phosphonate Anchoring Groups.
AB  - New catecholate ligands containing protected phosphonate anchoring groups in the
      4-position of the catecholate ring were synthesized. The catechol 4
      diethoxyphosphorylbenzene-1,2-diol, ((Et)phoscat)H2, was prepared in three steps
      from pyrocatechol; whereas, the catechol 4-(diethoxyphosphorylmethyl)benzene-1,2
      diol, ((Et)Bnphoscat)H2, containing a methylene spacer between the catecholate
      ring and phosphonate anchor, was prepared from protocatechuic acid in six linear
      steps. Both catechol derivatives were further elaborated to their trimethylsilyl
      protected counterparts to facilitate their binding to nanocrystalline metal
      oxides. Electronic spectroscopy and cyclic voltammetry were used to probe the
      electronic properties of the phosphonate-functionalized catecholates in charge
      transfer complexes of the general formula (catecholate)Pd(pdi) (pdi = N,N'
      bis(mesityl)phenanthrene-9,10-diimine). These studies show that attachment of the
      phosphonate anchor directly to the 4-position of the ((Et)phoscat)(2-) ligand
      significantly perturbs the donor ability of the catecholate ligand; however,
      incorporation of a single methylene spacer group in ((Et)Bnphoscat)(2-) helps to
      isolate catecholate from the electron-withdrawing phosphonate group. 

PMID- 26200757
TI  - Quantitative proteomics analyses of activation states of human THP-1 macrophages.
AB  - Macrophages display large functional and phenotypical plasticity. They can adopt
      a broad range of activation states depending on their microenvironment. Various
      surface markers are used to characterize these differentially polarized
      macrophages. However, this is not informative for the functions of the
      macrophage. In order to have a better understanding of the functional changes of
      macrophages upon differential polarization, we studied differences in LPS- and
      IL4-stimulated macrophages. The THP-1 human monocytic cell line, was used as a
      model system. Cells were labeled, differentiated and stimulated with either LPS
      or IL-4 in a quantitative SILAC proteomics set-up. The resulting sets of proteins
      were functionally clustered. LPS-stimulated macrophages show increased secretion
      of proinflammatory peptides, leading to increased pressure on protein
      biosynthesis and processing. IL4-stimulated macrophages show upregulation of cell
      adhesion and extracellular matrix remodeling. Our approach provides an integrated
      view of polarization-induced functional changes and proves useful for studying
      functional differences between subsets of macrophages. Moreover, the identified
      polarization specific proteins may contribute to a better characterization of
      different activation states in situ and their role in various inflammatory
      processes. 

PMID- 26200758
TI  - Synthesis, Internal Structure, and Formation Mechanism of Monodisperse Tin
      Sulfide Nanoplatelets.
AB  - Tin sulfide nanoparticles have a great potential for use in a broad range of
      applications related to solar energy conversion (photovoltaics, photocatalysis),
      electrochemical energy storage, and thermoelectrics. The development of chemical
      synthesis methods allowing for the precise control of size, shape, composition,
      and crystalline phase is essential. We present a novel approach giving access to
      monodisperse square SnS nanoplatelets, whose dimensions can be adjusted in the
      range of 4-15 nm (thickness) and 15-100 nm (edge length). Their growth occurs via
      controlled assembly of initially formed polyhedral seed nanoparticles, which
      themselves originate from an intermediate tetrachlorotin-oleate complex. The SnS
      nanoplatelets crystallize in the alpha-SnS orthorhombic herzenbergite structure
      (space group Pnma) with no evidence of secondary phases. Electron tomography,
      high angle annular dark field scanning transmission electron microscopy and
      electron diffraction combined with image simulations evidence the presence of
      ordered Sn vacancy rich (100) planes within the SnS nanoplatelets, in accordance
      with their slightly S-rich composition observed. When using elemental sulfur
      instead of thioacetamide as the sulfur source, the same reaction yields small (2
      3 nm) spherical SnS2 nanoparticles, which crystallize in the berndtite 4H
      crystallographic phase (space group P3m1). They exhibit quantum confinement (E(g)
      = 2.8 eV vs 2.2 eV in the bulk) and room temperature photoluminescence. By means
      of electrochemical measurements we determined their electron affinity EA = -4.8
      eV, indicating the possibility to use them as a substitute for CdS (EA = -4.6 eV)
      in the buffer layer of thin film solar cells.

PMID- 26200759
TI  - Increased disease activity, severity and autoantibody positivity in rheumatoid
      arthritis patients with co-existent bronchiectasis.
AB  - AIM: Patients with rheumatoid arthritis (RA) and co-existent bronchiectasis
      (BRRA) have a five-fold increased mortality compared to rheumatoid arthritis
      alone. Yet previous studies have found no difference in clinical and serological
      markers of RA disease severity between BRRA patients and RA alone. However, RA
      disease activity measures such as Disease Activity Score of 28 joints - C
      reactive protein (DAS28-CRP) and anti-cyclic citrullinated peptide antibodies
      (anti-CCP) have not been studied, so we assessed these parameters in patients
      with BRRA and RA alone. METHODS: BRRA patients (n = 53) had high-resolution
      computed tomography proven bronchiectasis without any interstitial lung disease
      and >= 2 respiratory infections/year. RA alone patients (n = 50) had no clinical
      or radiological evidence of lung disease. DAS28-CRP, rheumatoid factor
      (immunoglobulin M) and anti-CCP were measured in all patients, together with
      detailed clinical and radiology records. RESULTS: In BRRA, bronchiectasis
      predated RA in 58% of patients. BRRA patients had higher DAS28 scores (3.51 vs.
      2.59), higher levels of anti-CCP (89% vs. 46%) and rheumatoid factor (79% vs.
      52%) (P = 0.003) compared to RA alone. Where hand and foot radiology findings
      were recorded, 29/37 BRRA (78%) and 13/30 (43%) RA alone had evidence of erosive
      change (P = 0.003). There were no significant differences between groups in
      smoking history or disease-modifying anti-rheumatic drug/biologic therapy.
      CONCLUSIONS: Increased levels of RA disease activity, severity and RA
      autoantibodies are demonstrated in patients with RA and co-existent
      bronchiectasis compared to patients with RA alone, despite lower tobacco
      exposure. This study demonstrates that BRRA is a more severe systemic disease
      than RA alone.

PMID- 26200760
TI  - In Situ Polymerized PAN-Assisted S/C Nanosphere with Enhanced High-Power
      Performance as Cathode for Lithium/Sulfur Batteries.
AB  - Carbonaceous and polymer materials are extensively employed as conductor and
      container to encapsulate sulfur particles and limit polysulfide dissolution. Even
      so, high-power performance is still far from satisfaction due to the expansion
      and collapse of the electrode materials during thousands of charge-discharge
      process. Herein, it is found that colloidal carbon sphere with high elastic
      coefficient can be utilized as a framework to load sulfur, which can trap soluble
      polysulfides species in the pores within the sphere and efficaciously improve the
      electronic conductivity of the cathode. After modified by polyaniline (PAN)
      through in situ polymerization, PAN-assisted S/C nanosphere (PSCs-73, with 73 wt
      % sulfur) effectively minimize polysulfide diffusion, enhance the electron
      transfer rate and overcome the problem of volume expansion. The fabricated PSCs
      73 cell shows outstanding long high-power cycling capability over 2500
      charge/discharge cycles with a capacity decay of 0.01% per cycle at 5 C.
      Substantially, this composite can drive 2.28 W white indicators of LED robustly
      after minutes of charging by three lithium batteries in series, showing a
      promising potential application in the future. 

PMID- 26200761
TI  - Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced
      non-small cell lung cancer?
AB  - BACKGROUND: The aim of this study was to investigate oxidative stress and
      thiol/disulfide status with a novel automated homeostasis assay in advanced non
      small cell lung cancer (NSCLC). METHODS: Thirty-five patients with advanced
      NSCLC, who had been newly diagnosed and previously untreated, and 35 healthy
      subjects were chosen for the study. We measured plasma total thiol (-SH+-S-S-),
      native thiol (thiol) (-SH), and disulfide (-S-S-) levels in the patients with
      NSCLC and the healthy subjects. The thiol/disulfide (-SH/-S-S-) ratio was also
      calculated. RESULTS: Statistically significant differences between the patient
      group and the control group were detected for the thiol/disulfide parameters. The
      mean native thiol, total thiol, and disulfide levels were significantly lower in
      the group with advanced stage NSCLC. The cut-off value was 313 and 13.8 for
      native thiol and disulfide, respectively. Median overall survival (OS) was
      significantly shorter in patients with low native thiol and disulfide levels
      according to the cut-off value (respectively, P = 0.001; P = 0.006). Native
      thiol, total thiol, and disulfide levels were correlated with Karnofsky
      performance status (KPS), OS, and age. Additionally, hierarchical regression
      analyses showed gender, KPS, lung metastases, and plasma native thiol levels were
      the determinants of OS in the final model. CONCLUSION: These results suggest that
      in advanced stage NSCLC, the native thiol, total thiol, and disulfide levels
      decrease, while the native thiol/disulfide ratio does not change. Low levels of
      thiol/disulfide parameters are related to tumor aggressiveness and may predict a
      poor outcome for patients with NSCLC.

PMID- 26200762
TI  - Evidence for Active Electrolyte Transport by Two-Dimensional Monolayers of Human
      Salivary Epithelial Cells.
AB  - Functional reconstruction of lost tissue by regenerative therapy of salivary
      glands would be of immense benefit following radiotherapy or in the treatment of
      Sjogren's syndrome. The purpose of this study was to develop primary cultures of
      human salivary gland cells as potential regenerative resources and to
      characterize their acinar/ductal phenotype using electrophysiological
      measurements of ion transport. Human salivary gland cultures were prepared either
      from adherent submandibular gland cells (huSMG) or from mixed adherent and
      nonadherent cells (PTHSG) and were cultivated in Hepato-STIM or minimum essential
      medium (MEM). Expression of key epithelial marker proteins was determined by
      quantitative reverse transcription polymerase chain reaction (RT-PCR).
      Transepithelial electrical resistance (TER) was monitored following seeding the
      cells on Transwell membranes. Transepithelial ion transport was estimated by
      short-circuit current (Isc) measurements in an Ussing chamber. Both huSMG and
      PTHSG cells showed epithelial characteristics when cultivated in Hepato-STIM,
      while fibroblast-like elements dominated in MEM. Compared to intact tissue,
      cultivation of the cells resulted in substantial decreases in AQP5 and NKCC1
      expression and moderate increases in claudin-1 and ENaC expression. Both cultures
      achieved high TER and transepithelial electrolyte movement in Hepato-STIM, but
      not in MEM. The Isc was substantially reduced by basolateral Cl(-) and
      bicarbonate withdrawal, indicating the involvement of basolateral-to-apical anion
      transport, and by the blockade of apical ENaC by amiloride, indicating the
      involvement of apical-to-basolateral Na(+) transport. An almost complete
      inhibition was observed following simultaneous ENaC block and withdrawal of the
      two anions. Isc was enhanced by either apical adenosine triphosphate (ATP) or
      basolateral carbachol application, but not by forskolin, confirming the expected
      role of Ca(2+)-activated regulatory pathways in electrolyte secretion. Inhibition
      of basolateral NKCC1 by bumetanide reduced the response to ATP, indicating the
      active involvement of this transporter in Cl(-) secretion. In conclusion, we have
      demonstrated that both PTHSG and huSMG primary cultures cultivated in Hepato-STIM
      form two-dimensional monolayers in vitro on permeable supports and achieve active
      vectorial transepithelial electrolyte transport. The presence of both basolateral
      to-apical anion fluxes and an apical-to-basolateral Na(+) flux indicates both
      acinar and ductal characteristics. With further refinement, this model should
      provide a firm basis for new interventions to correct salivary gland dysfunction.

PMID- 26200763
TI  - Untargeted metabolomics in doping control: detection of new markers of
      testosterone misuse by ultrahigh performance liquid chromatography coupled to
      high-resolution mass spectrometry.
AB  - The use of untargeted metabolomics for the discovery of markers is a promising
      and virtually unexplored tool in the doping control field. Hybrid quadrupole time
      of-flight (QTOF) and hybrid quadrupole Orbitrap (Q Exactive) mass spectrometers,
      coupled to ultrahigh pressure liquid chromatography, are excellent tools for this
      purpose. In the present work, QTOF and Q Exactive have been used to look for
      markers for testosterone cypionate misuse by means of untargeted metabolomics.
      Two different groups of urine samples were analyzed, collected before and after
      the intramuscular administration of testosterone cypionate. In order to avoid
      analyte losses in the sample treatment, samples were just 2-fold diluted with
      water and directly injected into the chromatographic system. Samples were
      analyzed in both positive and negative ionization modes. Data from both systems
      were treated under untargeted metabolomic strategies using XCMS application and
      multivariate analysis. Results from the two mass spectrometers differed in the
      number of detected features, but both led to the same potential marker for the
      particular testosterone ester misuse. The in-depth study of the MS and MS/MS
      behavior of this marker allowed for the establishment of 1-cyclopentenoylglycine
      as a feasible structure. The putative structure was confirmed by comparison with
      synthesized material. This potential marker seems to come from the metabolism of
      the cypionic acid release after hydrolysis of the administered ester. Its
      suitability for doping control has been evaluated. 

PMID- 26200765
TI  - Tissue engineering and microRNAs: future perspectives in regenerative medicine.
AB  - INTRODUCTION: Tissue engineering is a growing area of biomedical research,
      holding great promise for a broad range of potential applications in the field of
      regenerative medicine. In recent decades, multiple tissue engineering strategies
      have been adopted to mimic and improve specific biological functions of tissues
      and organs, including biomimetic materials, drug-releasing scaffolds, stem cells,
      and dynamic culture systems. MicroRNAs (miRNAs), noncoding small RNAs that
      negatively regulate the expression of downstream target mRNAs, are considered a
      novel class of molecular targets and therapeutics that may play an important role
      in tissue engineering. AREAS COVERED: Herein, we highlight the latest
      achievements in regenerative medicine, focusing on the role of miRNAs as key
      modulators of gene expression, stem cell self-renewal, proliferation and
      differentiation, and eventually in driving cell fate decisions. Finally, we will
      discuss the contribution of miRNAs in regulating the rearrangement of the tissue
      microenvironment and angiogenesis, and the range of strategies for miRNA delivery
      into target cells and tissues. EXPERT OPINION: Manipulation of miRNAs is an
      alternative approach and an attractive strategy for controlling several aspects
      of tissue engineering, although some issues concerning their in vivo effects and
      optimal delivery methods still remain uncovered.

PMID- 26200764
TI  - Transitions in Care in a Nationally Representative Sample of Older Americans with
      Dementia.
AB  - OBJECTIVES: To describe transitions in care for older adults with dementia
      identified from a nationally representative cohort and to describe transition
      rates in those with more-severe levels of cognitive and functional impairment.
      DESIGN: Longitudinal cohort study. SETTING: Health and Retirement Study (HRS).
      PARTICIPANTS: HRS respondents aged 65 and older whose survey data were linked
      with Medicare claims from 1999 to 2008 (N = 16,186). MEASUREMENTS: Transitions in
      care between home, home with formal services, hospital, and nursing facility
      care; cognitive function; activities of daily living; and mortality. RESULTS: The
      3,447 (21.3%) HRS subjects who were ever diagnosed with dementia experienced
      frequent transitions. Of subjects transitioning from a hospital stay, 52.2%
      returned home without home care services, and 33.8% transitioned to a nursing
      facility. Of subjects transitioning from a nursing facility, 59.2% transitioned
      to the hospital, and 25.3% returned home without services. There were 2,139
      transitions to death, and 58.7% of HRS subjects with dementia died at home. Even
      in persons with moderate to severe dementia, multiple transitions in care were
      documented, including transitions from the hospital to home and back to the
      hospital. CONCLUSION: In this nationally representative sample of older adults,
      subjects diagnosed with dementia experience frequent transitions. Persons with
      dementia who are cared for at home and who transition back to home often have
      moderate to severe impairments in function and cognition.

PMID- 26200767
TI  - Unsupervised Neural Network Quantifies the Cost of Visual Information Processing.
AB  - Untrained, "flower-naive" bumblebees display behavioural preferences when
      presented with visual properties such as colour, symmetry, spatial frequency and
      others. Two unsupervised neural networks were implemented to understand the
      extent to which these models capture elements of bumblebees' unlearned visual
      preferences towards flower-like visual properties. The computational models,
      which are variants of Independent Component Analysis and Feature-Extracting
      Bidirectional Associative Memory, use images of test-patterns that are identical
      to ones used in behavioural studies. Each model works by decomposing images of
      floral patterns into meaningful underlying factors. We reconstruct the original
      floral image using the components and compare the quality of the reconstructed
      image to the original image. Independent Component Analysis matches behavioural
      results substantially better across several visual properties. These results are
      interpreted to support a hypothesis that the temporal and energetic costs of
      information processing by pollinators served as a selective pressure on floral
      displays: flowers adapted to pollinators' cognitive constraints. 

PMID- 26200768
TI  - Higher Dead Space Is Associated With Increased Mortality in Critically Ill
      Children.
AB  - OBJECTIVE: Elevated dead space has been consistently associated with increased
      mortality in adults with respiratory failure. In children, the evidence for this
      association is more limited. We sought to investigate the association between
      dead space and mortality in mechanically ventilated children. DESIGN: Single
      center retrospective review. SETTING: Tertiary care pediatric critical care unit.
      PATIENTS: Seven hundred twelve mechanically ventilated children with an arterial
      catheter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The end-tidal
      alveolar dead space fraction ((PaCO2-PETCO2)/PaCO2), a dead space marker, was
      calculated with each arterial blood gas. The initial end-tidal alveolar dead
      space fraction (first arterial blood gas after intubation) (per 0.1 unit
      increase: odds ratio, 1.59; 95% CI, 1.40-1.81) and day 1 mean end-tidal alveolar
      dead space fraction (odds ratio, 1.95; 95% CI, 1.66-2.30) were associated with
      mortality. The relationship between both initial and day 1 mean end-tidal
      alveolar dead space fraction and mortality held in multivariate modeling after
      controlling for any of the following individually: PaO2/FIO2, oxygenation index,
      24-hour maximal inotrope score, and Pediatric Risk of Mortality III (all p<0.01),
      although end-tidal alveolar dead space fraction was no longer significant after
      controlling for the combination of oxygenation index, 24-hour maximal inotrope
      score, and Pediatric Risk of Mortality III. In 217 children with acute hypoxemic
      respiratory failure, initial end-tidal alveolar dead space fraction (per 0.1 unit
      increase odds ratio, 1.38; 95% CI, 1.14-1.67) and day 1 mean end-tidal alveolar
      dead space fraction (per 0.1 unit increase odds ratio, 1.60; 95% CI, 1.27-2.0)
      were associated with mortality. Day 1 mean end-tidal alveolar dead space fraction
      remained associated with mortality after controlling individually for any of the
      following in multivariate models: PaO2/FIO2, oxygenation index, and 24-hour
      maximal inotrope score (p<=0.02), although end-tidal alveolar dead space fraction
      was no longer significant after controlling for the combination of oxygenation
      index, 24-hour maximal inotrope score, and Pediatric Risk of Mortality III.
      CONCLUSIONS: Increased dead space is associated with higher mortality in
      critically ill children, although it is no longer independently associated with
      mortality after controlling for severity of oxygenation defect, inotrope use, and
      severity of illness. However, because end-tidal alveolar dead space fraction is
      easy to calculate at the bedside, it may be useful for risk stratification and
      severity-of-illness scores.

PMID- 26200769
TI  - Development of Non-C2-symmetric ProPhenol Ligands. The Asymmetric Vinylation of N
      Boc Imines.
AB  - The development and application of a new generation of non-C2-symmetric ProPhenol
      ligands is reported herein. Rational design of the ProPhenol ligand paved the way
      to the first catalytic and asymmetric vinylation of N-Boc imines via
      hydrozirconation giving rise to valuable allylic amines in excellent yields and
      enantioselectivities. The utility of this method was demonstrated by developing
      the shortest reported asymmetric synthesis of the selective serotonine reuptake
      inhibitor (SSRI) (-)-dapoxetine. 

PMID- 26200770
TI  - In-Pipeline Stenosis: Incidence, Predictors, and Clinical Outcomes.
AB  - BACKGROUND: The Pipeline Embolization Device is a widely utilized flow diverter
      in the treatment of intracranial aneurysms. OBJECTIVE: To assess the incidence,
      clinical significance, predictors, and outcomes of in-Pipeline stenosis (IPS).
      METHODS: Angiographic studies in 139 patients treated between 2011 and 2013 were
      independently reviewed by 2 authors for the presence of IPS. Multivariable
      logistic regression analysis was conducted to determine predictors of IPS.
      RESULTS: A total of 21 (15.8%) patients demonstrated some degree of IPS during
      the follow-up period at a mean time point of 6.7 months (range, 3-24 months). The
      stenosis was mild (<50%) in 11 patients, moderate (50%-75%) in 5, and severe
      (>75%) in 6. None were symptomatic or required further intervention. Sixteen of
      these 22 patients (73%) had IPS detected within 6 months. IPS was noted in 7.6%
      (1/13) of patients with posterior circulation aneurysms vs 16.7% (21/126) of
      those with anterior circulation aneurysms (P = .03). The rate of IPS was 60%
      (3/5) in patients who did not receive aspirin vs only 14.2% (19/134) in those who
      received aspirin (P = .02). In multivariable analysis, no aspirin therapy (odds
      ratio, 10.0; 95% confidence interval, 1.4-67.7; P = .02) and internal carotid
      artery aneurysm location (odds ratio, 3.1; 95% confidence interval, 1.1-8.8; P =
      .03) were strong independent predictors of IPS. CONCLUSION: IPS is a common,
      early, and mostly benign complication. Patients with internal carotid artery
      aneurysms are more likely to develop IPS. Aspirin plays a key role in preventing
      IPS. The results of this study further support the safety of flow diverters.
      ABBREVIATIONS: IPS, in-Pipeline stenosisPED, Pipeline Embolization Device.

PMID- 26200771
TI  - Thalamotomy-Like Effects From Partial Removal of a Ventral Intermediate Nucleus
      Deep Brain Stimulator Lead in a Patient With Essential Tremor: Case Report.
AB  - BACKGROUND AND IMPORTANCE: The ventral intermediate nucleus of the thalamus is a
      primary target of deep brain stimulation (DBS) in patients with essential tremor.
      Despite reliable control of contralateral tremor, there is sometimes a need for
      lead revision in cases of infection, hardware malfunction, or failure to relieve
      symptoms. Here, we present the case of a patient undergoing revision after
      ventral intermediate nucleus (Vim) DBS failed to control his tremor. During the
      electrode removal, the distal portion of the lead was found to be tightly
      adherent to tissue within the deep brain. Partial removal of the electrode in
      turn caused weakness, paresthesias, and tremor control similar to the effects
      produced by thalamotomy or thalamic injury. CLINICAL PRESENTATION: A 48-year-old
      man with essential tremor had bilateral Vim DBS leads implanted 10 years earlier
      but had poor control of his tremor and ultimately opted for surgical revision
      with lead placement in the zona incerta. During attempted removal of his right
      lead, the patient became somnolent with contralateral weakness and paresthesias.
      The procedure was aborted, and postoperative neuroimaging was immediately
      obtained, showing no signs of stroke or hemorrhage. The patient had almost
      complete control of his left arm tremor postoperatively, and his weakness soon
      resolved. CONCLUSION: To the best of our knowledge, this is the first reported
      case of cerebral injury after DBS revision and offers insights into the mechanism
      of high-frequency electric stimulation compared with lesions. That is, although
      high-frequency stimulation failed to control this patient's tremor, thalamotomy
      like injury was completely effective.

PMID- 26200772
TI  - Silent Arteriovenous Malformation Hemorrhage and the Recognition of "Unruptured"
      Arteriovenous Malformation Patients Who Benefit From Surgical Intervention.

PMID- 26200773
TI  - In Reply: Silent Arteriovenous Malformation Hemorrhage and the Recognition of
      "Unruptured" Arteriovenous Malformation Patients Who Benefit From Surgical
      Intervention.

PMID- 26200774
TI  - How Does Alkali Aid Protein Extraction in Green Tea Leaf Residue: A Basis for
      Integrated Biorefinery of Leaves.
AB  - Leaf protein can be obtained cost-efficiently by alkaline extraction, but overuse
      of chemicals and low quality of (denatured) protein limits its application. The
      research objective was to investigate how alkali aids protein extraction of green
      tea leaf residue, and use these results for further improvements in alkaline
      protein biorefinery. Protein extraction yield was studied for correlation to
      morphology of leaf tissue structure, protein solubility and hydrolysis degree,
      and yields of non-protein components obtained at various conditions. Alkaline
      protein extraction was not facilitated by increased solubility or hydrolysis of
      protein, but positively correlated to leaf tissue disruption. HG pectin, RGII
      pectin, and organic acids were extracted before protein extraction, which was
      followed by the extraction of cellulose and hemi-cellulose. RGI pectin and lignin
      were both linear to protein yield. The yields of these two components were 80%
      and 25% respectively when 95% protein was extracted, which indicated that RGI
      pectin is more likely to be the key limitation to leaf protein extraction. An
      integrated biorefinery was designed based on these results. 

PMID- 26200775
TI  - Significant Artifact Reduction at 1.5T and 3T MRI by the Use of a Cochlear
      Implant with Removable Magnet: An Experimental Human Cadaver Study.
AB  - OBJECTIVE: Cochlear implants (CIs) are standard treatment for postlingually
      deafened individuals and prelingually deafened children. This human cadaver study
      evaluated diagnostic usefulness, image quality and artifacts in 1.5T and 3T
      magnetic resonance (MR) brain scans after CI with a removable magnet. METHODS:
      Three criteria (diagnostic usefulness, image quality, artifacts) were assessed at
      1.5T and 3T in five cadaver heads with CI. The brain magnetic resonance scans
      were performed with and without the magnet in situ. The criteria were analyzed by
      two blinded neuroradiologists, with focus on image distortion and limitation of
      the diagnostic value of the acquired MR images. RESULTS: MR images with the
      magnet in situ were all compromised by artifacts caused by the CI. After removal
      of the magnet, MR scans showed an unequivocal artifact reduction with significant
      improvement of the image quality and diagnostic usefulness, both at 1.5T and 3T.
      Visibility of the brain stem, cerebellopontine angle, and parieto-occipital lobe
      ipsilateral to the CI increased significantly after magnet removal. CONCLUSIONS:
      The results indicate the possible advantages for 1.5T and 3T MR scanning of the
      brain in CI carriers with removable magnets. Our findings support use of CIs with
      removable magnets, especially in patients with chronic intracranial pathologies.

PMID- 26200776
TI  - Dual-signal amplified electrochemiluminescence immunoassay for salbutamol based
      on quantum dots and gold nanoparticle-labeled horseradish peroxidase.
AB  - This study describes a novel electrochemical immunosensor to amplify the
      electrochemiluminescence (ECL) signal for the ultrasensitive detection of
      salbutamol (SAL) using quantum dots (QDs) and gold nanoparticle (AuNP) conjugated
      horseradish peroxidase (HRP). The electrochemical detection was based on the HRP
      catalyzed consumption of self-produced H2O2, which has been extensively used as a
      co-reactant of QDs, by o-phenylenediamine (OPD). The enzymatic reaction rate is
      proportional to the amount of HRP bound to the electrode. In the presence of a
      SAL standard solution, the immobilized SAL coating antigens competed with the SAL
      solution for the Ab-AuNPs-HRP complexes. With an increase in the SAL
      concentration, the amount of immobilized HRP decreases, which leads to an
      increase in the ECL intensity. Under optimized conditions, the ECL intensity
      changes linearly with the logarithm of the SAL concentration in the range of 0.05
      500 ng mL(-1) with a detection limit of 0.017 ng mL(-1) (S/N = 3). The ECL
      immunosensor possesses high sensitivity, satisfactory reproducibility and
      selectivity, and may provide a feasible route for practical application. 

PMID- 26200777
TI  - Raspberry pulp polysaccharides inhibit tumor growth via immunopotentiation and
      enhance docetaxel chemotherapy against malignant melanoma in vivo.
AB  - It has been reported previously that the systemic efficacy of chemotherapeutic
      agents is substantially restricted for some cancer types, including malignant
      melanoma. Therefore, the development of more effective treatment modalities
      remains a critical, albeit elusive, goal in anticancer therapy. The study
      presented here evaluates the antitumor activity of raspberry pulp polysaccharides
      (RPPs) against malignant melanoma using a murine tumor-bearing model.
      Furthermore, the underlying mechanism of this antitumor activity has also been
      investigated. The results show that while RPP exhibits no direct cytotoxic effect
      on HT-29, MGC-803, HeLa, Bel-7402, L02 and B16F10 cells in vitro, it does
      demonstrate a dose-dependent growth inhibition of melanoma in vivo with an
      inhibition ratio of 59.95% at a dose of 400 mg kg(-1). Besides this, the body
      weight and spleen index in tumor-bearing mice have also been improved in RPP
      treated groups. RPP is also found to induce splenocyte proliferation and is able
      to upregulate the activity of immune-related enzymes, including acid phosphatase
      (ACP), alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and superoxide
      dismutase (SOD) in the spleen of tumor-bearing mice. The levels of tumor necrosis
      factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and interleukin 2 (IL-2)
      in the serum of tumor-bearing mice show to be effectively increased upon RPP
      treatment. Histopathological analyses show that RPP induces tumor tissue necrosis
      by increasing inflammatory cell infiltration and causes no lesions to liver and
      kidney tissues. Remarkably, RPP further enhances the antitumor effect of the
      chemotherapeutic drug docetaxel and alleviates docetaxel-induced liver and kidney
      lesions in tumor-bearing mice. These findings indicate that RPP exhibits
      antitumor activity in vivo against malignant melanoma, partly by enhancing the
      cellular immune response of the host organism. In summary, RPP features critical
      properties to potentially find use as an immunopotentiating agent or as a
      chemotherapy adjuvant agent for the treatment of malignant melanoma. 

PMID- 26200778
TI  - Shedding New Light on the 18th Dynasty Mummies of the Royal Architect Kha and His
      Spouse Merit.
AB  - The mummies of Kha and his wife Merit were found intact in an undisturbed tomb in
      western Thebes near the ancient workers' village of Deir el-Medina. Previous MDCT
      (this abbreviation needs spelling out) investigations showed that the bodies of
      Kha and Merit did not undergo classical royal 18th Dynasty artificial
      mummification, which included removal of the internal organs. It was, therefore,
      concluded that the retention of the viscera in the body, combined with an absence
      of canopic jars in the burial chamber, meant the couple underwent a short and
      shoddy funerary procedure, despite their relative wealth at death. Nevertheless,
      all internal organs - brain, ocular bulbs/ocular nerves, thoracic and abdominal
      organs - showed a very good state of preservation, which contradicts the previous
      interpretation above. In order to better understand the type of mummification
      used to embalm these bodies, both wrapped mummies were reinvestigated using new
      generation X-ray imaging and chemical microanalyses Here we provide evidence that
      both individuals underwent a relatively high quality of mummification,
      fundamentally contradicting previous understanding. Elucidated "recipes", whose
      components had anti-bacterial and anti-insecticidal properties, were used to
      treat their bodies. The time and effort undoubtedly employed to embalm both Kha
      and Merit and the use of imported costly resins, notably Pistacia, do not support
      the previously held view that the two individuals were poorly mummified. Despite
      a lack of evisceration, the approach clearly allowed their in situ preservation
      as well as affording a fairly successful mummification. 

PMID- 26200779
TI  - Geo-Referenced, Abundance Calibrated Ocean Distribution of Chinook Salmon
      (Oncorhynchus tshawytscha) Stocks across the West Coast of North America.
AB  - Understanding seasonal migration and localized persistence of populations is
      critical for effective species harvest and conservation management. Pacific
      salmon (genus Oncorhynchus) forecasting models predict stock composition,
      abundance, and distribution during annual assessments of proposed fisheries
      impacts. Most models, however, fail to account for the influence of biophysical
      factors on year-to-year fluctuations in migratory distributions and stock
      specific survival. In this study, the ocean distribution and relative abundance
      of Chinook salmon (O. tshawytscha) stocks encountered in the California Current
      large marine ecosystem, U.S.A were inferred using catch-per-unit effort (CPUE)
      fisheries and genetic stock identification data. In contrast to stock
      distributions estimated through coded-wire-tag recoveries (typically limited to
      hatchery salmon), stock-specific CPUE provides information for both wild and
      hatchery fish. Furthermore, in contrast to stock composition results, the stock
      specific CPUE metric is independent of other stocks and is easily interpreted
      over multiple temporal or spatial scales. Tests for correlations between stock
      specific CPUE and stock composition estimates revealed these measures diverged
      once proportional contributions of locally rare stocks were excluded from data
      sets. A novel aspect of this study was collection of data both in areas closed to
      commercial fisheries and during normal, open commercial fisheries. Because
      fishing fleet efficiency influences catch rates, we tested whether CPUE differed
      between closed area (non-retention) and open area (retention) data sets. A weak
      effect was indicated for some, but not all, analyzed cases. Novel visualizations
      produced from stock-specific CPUE-based ocean abundance facilitates consideration
      of how highly refined, spatial and genetic information could be incorporated in
      ocean fisheries management systems and for investigations of biogeographic
      factors that influence migratory distributions of fish. 

PMID- 26200781
TI  - The Likelihood of Experiencing Relative Poverty over the Life Course.
AB  - Research on poverty in the United States has largely consisted of examining cross
      sectional levels of absolute poverty. In this analysis, we focus on understanding
      relative poverty within a life course context. Specifically, we analyze the
      likelihood of individuals falling below the 20th percentile and the 10th
      percentile of the income distribution between the ages of 25 and 60. A series of
      life tables are constructed using the nationally representative Panel Study of
      Income Dynamics data set. This includes panel data from 1968 through 2011.
      Results indicate that the prevalence of relative poverty is quite high.
      Consequently, between the ages of 25 to 60, 61.8 percent of the population will
      experience a year below the 20th percentile, and 42.1 percent will experience a
      year below the 10th percentile. Characteristics associated with experiencing
      these levels of poverty include those who are younger, nonwhite, female, not
      married, with 12 years or less of education, or who have a work disability. 

PMID- 26200780
TI  - Dissolved Oxygen Sensor in Animal-Borne Instruments: An Innovation for Monitoring
      the Health of Oceans and Investigating the Functioning of Marine Ecosystems.
AB  - The current decline in dissolved oxygen concentration within the oceans is a
      sensitive indicator of the effect of climate change on marine environment.
      However the impact of its declining on marine life and ecosystems' health is
      still quite unclear because of the difficulty in obtaining in situ data,
      especially in remote areas, like the Southern Ocean (SO). Southern elephant seals
      (Mirounga leonina) proved to be a relevant alternative to the traditional
      oceanographic platforms to measure physical and biogeochemical structure of
      oceanic regions rarely observed. In this study, we use a new stage of development
      in biologging technology to draw a picture of dissolved oxygen concentration in
      the SO. We present the first results obtained from a dissolved oxygen sensor
      added to Argos CTD-SRDL tags and deployed on 5 female elephant seals at
      Kerguelen. From October 2010 and October 2011, 742 oxygen profiles associated
      with temperature and salinity measurements were recorded. Whether a part of the
      data must be considered cautiously, especially because of offsets and temporal
      drifts of the sensors, the range of values recorded was consistent with a
      concomitant survey conducted from a research vessel (Keops-2 project). Once
      again, elephant seals reinforced the relationship between marine ecology and
      oceanography, delivering essential information about the water masses properties
      and the biological status of the Southern Ocean. But more than the presentation
      of a new stage of development in animal-borne instrumentation, this pilot study
      opens a new field of investigation in marine ecology and could be enlarged in a
      near future to other key marine predators, especially large fish species like
      swordfish, tuna or sharks, for which dissolved oxygen is expected to play a
      crucial role in distribution and behaviour. 

PMID- 26200782
TI  - Prevalence and Severity of Myocardial Perfusion Imaging Abnormalities in Inmate
      Subjects.
AB  - AIM: We evaluated the prevalence and severity of myocardial perfusion
      abnormalities among inmates undergoing cardiac single-photon emission computed
      tomography. We also compared the results with those obtained in a cohort of non
      inmates. METHODS: Between January 2009 and December 2013, 2420 consecutive
      subjects (258 inmates and 2162 non-inmates) with suspected or known coronary
      artery disease underwent stress myocardial perfusion single-photon emission
      computed tomography (MPS) to our institution. The decision to submit inmates to
      MPS was taken by the physicians of the penal institutions or ordered by the court
      based on the survey of part. To account for differences in clinical
      characteristics between inmates and non-inmates, we created a propensity score
      matched cohort considering clinical variables and stress type. RESULTS: Before
      matching, inmates were younger and had higher prevalence of male gender, smoking,
      chest pain, and previous myocardial infarction or revascularization (all p <
      0.001). After matching, all characteristics were comparable in 258 inmates and
      258 non-inmates. The total amount of abnormal myocardium was similar in inmates
      and non-inmates before and after matching. Infarct size and severity were larger
      in inmates before (p < 0.001) and after (p < 0.01) matching and left ventricular
      ejection fraction was lower in inmates compared to non-inmates (p < 0.01).
      CONCLUSIONS: Detention is associated with larger infarct size compared to a
      general population of subjects referred to stress MPS also after matching for
      clinical variables and stress type. The similar prevalence of normal MPS in the
      matched cohort suggests that this imaging technique might be appropriate in
      inmates.

PMID- 26200783
TI  - Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors.
AB  - Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an
      important human bacterial pathogen that can cause invasive infections. Once it
      colonizes its exclusively human host, GAS needs to surmount numerous innate
      immune defense mechanisms, including opsonization by complement and consequent
      phagocytosis. Several strains of GAS bind to human-specific complement
      inhibitors, C4b-binding protein (C4BP) and/or Factor H (FH), to curtail
      complement C3 (a critical opsonin) deposition. This results in diminished
      activation of phagocytes and clearance of GAS that may lead to the host being
      unable to limit the infection. Herein we describe the course of GAS infection in
      three human complement inhibitor transgenic (tg) mouse models that examined each
      inhibitor (human C4BP or FH) alone, or the two inhibitors together (C4BPxFH or
      'double' tg). GAS infection with strains that bound C4BP and FH resulted in
      enhanced mortality in each of the three transgenic mouse models compared to
      infection in wild type mice. In addition, GAS manifested increased virulence in
      C4BPxFH mice: higher organism burdens and greater elevations of pro-inflammatory
      cytokines and they died earlier than single transgenic or wt controls. The
      effects of hu-C4BP and hu-FH were specific for GAS strains that bound these
      inhibitors because strains that did not bind the inhibitors showed reduced
      virulence in the 'double' tg mice compared to strains that did bind; mortality
      was also similar in wild-type and C4BPxFH mice infected by non-binding GAS. Our
      findings emphasize the importance of binding of complement inhibitors to GAS that
      results in impaired opsonization and phagocytic killing, which translates to
      enhanced virulence in a humanized whole animal model. This novel hu-C4BPxFH tg
      model may prove invaluable in studies of GAS pathogenesis and for developing
      vaccines and therapeutics that rely on human complement activation for efficacy. 

PMID- 26200784
TI  - Homologous prime-boost strategy with TgPI-1 improves the immune response and
      protects highly susceptible mice against chronic Toxoplasma gondii infection.
AB  - Subunit-based vaccines are safer than live or attenuated pathogen vaccines,
      although they are generally weak immunogens. Thus, proper combination of
      immunization strategies and adjuvants are needed to increase their efficacy. We
      have previously protected C3H/HeN mice from Toxoplasma gondii infection by
      immunization with the serine protease inhibitor-1 (TgPI-1) in combination with
      alum. In this work, we explore an original vaccination protocol that combines
      administration of recombinant TgPI-1 by intradermal and intranasal routes in
      order to enhance protection in the highly susceptible C57BL/6 strain. Mice primed
      intradermally with rTgPI-1 plus alum and boosted intranasally with rTgPI-1 plus
      CpG-ODN elicited a strong specific Th1/Th2 humoral response, along with a mucosal
      immune response characterized by specific-IgA in intestinal lavages. A positive
      cellular response of mesentheric lymph node cells and Th1/Th2 cytokine secretion
      in the ileon were also detected. When immunized mice were challenged with the
      cystogenic Me49 T. gondii strain, they displayed up to 62% reduction in brain
      parasite burden. Moreover, adoptive transfer of mesenteric lymph node cells from
      vaccinated to naive mice induced significant protection against infection. These
      results demonstrate that this strategy that combines the administration of TgPI-1
      by two different routes, intradermal priming and intranasal boost, improves
      protective immunity against T. gondii chronic infection in highly susceptible
      mice.

PMID- 26200785
TI  - The multiple and complex and changeable scenarios of the Trypanosoma cruzi
      transmission cycle in the sylvatic environment.
AB  - In this study, we report and discuss the results generated from over 20 years of
      studies of the Trypanosoma cruzi sylvatic transmission cycle. Our results have
      uncovered new aspects and reviewed old concepts on issues including reservoirs,
      true generalist species, association of mammalian species with distinct discrete
      typing units - DTUs, distribution of T. cruzi genotypes in the wild, mixed
      infections, and T. cruzi transmission ecology. Using parasitological and
      serological tests, we examined T. cruzi infection in 7,285 mammalian specimens
      from nine mammalian orders dispersed all over the Brazilian biomes. The obtained
      T. cruzi isolates were characterized by mini-exon gene sequence polymorphism and
      PCR RFLP to identify DTUs. Infection by T. cruzi was detected by serological
      methods in 20% of the examined animals and isolated from 41% of those infected,
      corresponding to 8% of all the examined mammals. Each mammal taxon responded
      uniquely to T. cruzi infection. Didelphis spp. are able to maintain high and long
      lasting parasitemias (positive hemocultures) caused by TcI but maintain and
      rapidly control parasitemias caused by TcII to almost undetectable levels. In
      contrast, the tamarin species Leontopithecus rosalia and L. chrysomelas maintain
      long-lasting and high parasitemias caused by TcII similarly to Philander sp. The
      coati Nasua nasua maintains high parasitemias by both parental T. cruzi DTUs TcI
      or TcII and by TcII/TcIV (formerly Z3) at detectable levels. Wild and domestic
      canidae seem to display only a short period of reservoir competence. T. cruzi
      infection was demonstrated in the wild canid species Cerdocyon thous and
      Chrysocyon brachyurus, and positive hemoculture was obtained in one hyper
      carnivore species (Leopardus pardalis), demonstrating that T. cruzi transmission
      is deeply immersed in the trophic net. T. cruzi DTU distribution in nature did
      not exhibit any association with a particular biome or habitat. TcI predominates
      throughout (58% of the T. cruzi isolates); however, in spite of being
      significantly less frequent (17%), TcII is also widely distributed. Concomitant
      DTU infection occurred in 16% of infected mammals of all biomes and included
      arboreal and terrestrial species, as well as bats. TcI/TcII concomitant infection
      was the most common and widely dispersed, with mixed TcI/TcII infections
      especially common in coatis and in Didelphimorphia. The second most common
      pattern of concomitant infection was TcI/TcIV, observed in Chiroptera,
      Didelphimorphia and Primates. Taken together, our results demonstrate the
      complexity of T. cruzi reservoir system and its transmission strategies,
      indicating that there is considerably more to be learned regarding ecology of T.
      cruzi. 

PMID- 26200786
TI  - Dermatophytosis in patients with human immunodeficiency virus infection: clinical
      aspects and etiologic agents.
AB  - Dermatophytosis in individuals with human immunodeficiency virus infection seems
      to manifest with atypical, multiple, or extensive lesions more frequently. In
      addition, there are reports of presentations with little inflammation, called
      anergics. Less common etiologic agents have been isolated in these individuals,
      such as Microsporum species. To describe clinical aspects and etiologic agents of
      dermatophytosis in individuals with human immunodeficiency virus (HIV) infection.
      Patients with clinical diagnosis of dermatophytosis underwent scarification for
      mycological diagnosis through direct microscopic examination and fungal isolation
      in culture on Sabouraud dextrose agar. Sixty individuals had a clinical
      hypothesis of dermatophytosis. In 20 (33.3%) of the 60 patients, dermatophytosis
      was confirmed through a mycological study. Tinea corporis, diagnosed in 14
      patients, was the most frequent clinical form, followed by tinea unguium in 7,
      tinea cruris in 5, and tinea pedis in 1 patient. Most of the lesions of tinea
      corporis were anergic. Five patients with tinea unguium had involvement of
      multiple nails, with onychodystrophy as the predominant subtype. Multiple
      cutaneous lesions occurred in 3 patients and extensive cutaneous lesions in 4.
      Regarding the agent, Trichophyton rubrum was the most commonly isolated. The high
      occurrence of anergic skin lesions and involvement of multiple nails, especially
      as onychodystrophy, corroborates the hypothesis that atypical, disseminated, and
      more severe presentations are common in individuals with HIV infection. However,
      no Microsporum species was isolated even in atypical, extensive, or disseminated
      cases, in disagreement with previous reports. Therefore, the approach of squamous
      lesions in HIV-positive patients must include a mycological study, in view of the
      possibility of anergic dermatophytosis, to promote the introduction of a suitable
      therapeutic agent.

PMID- 26200787
TI  - Trypanosoma cruzi population dynamics in the Central Ecuadorian Coast.
AB  - Chagas disease is the most important parasitic disease in Latin America. The
      causative agent, Trypanosoma cruzi, displays high genetic diversity and
      circulates in complex transmission cycles among domestic, peridomestic and
      sylvatic environments. In Ecuador, Rhodnius ecuadoriensis is known to be the
      major vector species implicated in T. cruzi transmission. However, across vast
      areas of Ecuador, little is known about T. cruzi genetic diversity in relation to
      different parasite transmission scenarios. Fifty-eight T. cruzi stocks from the
      central Ecuadorian coast, most of them derived from R. ecuadoriensis, were
      included in the study. All of them were genotyped as T. cruzi discrete typing
      unit I (DTU TcI). Analysis of 23 polymorphic microsatellite loci through neighbor
      joining and discriminant analysis of principal components yielded broadly
      congruent results and indicate genetic subdivision between sylvatic and
      peridomestic transmission cycles. However, both analyses also suggest that any
      barriers are imperfect and significant gene flow between parasite subpopulations
      in different habitats exists. Also consistent with moderate partition and
      residual gene flow between subpopulations, the fixation index (FST) was
      significant, but of low magnitude. Finally, the lack of private alleles in the
      domestic/peridomestic transmission cycle suggests the sylvatic strains constitute
      the ancestral population. The T. cruzi population in the central Ecuadorian coast
      shows moderate tendency to subdivision according to transmission cycle. However,
      connectivity between cycles exists and the sylvatic T. cruzi population harbored
      by R. ecuadoriensis vectors appears to constitute a source from which the
      parasite invades human domiciles and their surroundings in this region. We
      discuss the implications these findings have for the planning, implementation and
      evaluation of local Chagas disease control interventions. 

PMID- 26200788
TI  - Genetic diversity of Trypanosoma cruzi in bats, and multilocus phylogenetic and
      phylogeographical analyses supporting Tcbat as an independent DTU (discrete
      typing unit).
AB  - Trypanosoma cruzi is a complex of phenotypically and genetically diverse isolates
      distributed in six discrete typing units (DTUs) designated as TcI-TcVI. Five
      years ago, T. cruzi isolates from Brazilian bats showing unique patterns of
      traditional ribosomal and spliced leader PCRs not clustering into any of the six
      DTUs were designated as the Tcbat genotype. In the present study, phylogenies
      inferred using SSU rRNA (small subunit of ribosomal rRNA), gGAPDH (glycosomal
      glyceraldehyde 3-phosphate dehydrogenase) and Cytb (cytochrome b) genes strongly
      supported Tcbat as a monophyletic lineage prevalent in Brazil, Panama and
      Colombia. Providing strong support for Tcbat, sequences from 37 of 47 nuclear and
      12 mitochondrial genes (retrieved from a draft genome of Tcbat) and reference
      strains of all DTUs available in databanks corroborated Tcbat as an independent
      DTU. Consistent with previous studies, multilocus analysis of most nuclear genes
      corroborated the evolution of T. cruzi from bat trypanosomes its divergence into
      two main phylogenetic lineages: the basal TcII; and the lineage clustering TcIV,
      the clade comprising TcIII and the sister groups TcI-Tcbat. Most likely, the
      common ancestor of Tcbat and TcI was a bat trypanosome. However, the results of
      the present analysis did not support Tcbat as the ancestor of all DTUs. Despite
      the insights provided by reports of TcIII, TcIV and TcII in bats, including
      Amazonian bats harbouring TcII, further studies are necessary to understand the
      roles played by bats in the diversification of all DTUs. We also demonstrated
      that in addition to value as molecular markers for DTU assignment, Cytb, ITS rDNA
      and the spliced leader (SL) polymorphic sequences suggest spatially structured
      populations of Tcbat. Phylogenetic and phylogeographical analyses, multiple
      molecular markers specific to Tcbat, and the degrees of sequence divergence
      between Tcbat and the accepted DTUs strongly support the definitive
      classification of Tcbat as a new DTU. 

PMID- 26200789
TI  - Evaluating the sterilizing effect of pyriproxyfen treated mosquito nets against
      Anopheles gambiae at different blood-feeding intervals.
AB  - Pyrethroid resistant malaria vectors are widespread throughout sub-Saharan Africa
      and new insecticides with different modes of action are urgently needed.
      Pyriproxyfen is a juvenile hormone mimic that reduces fecundity and fertility of
      adult Anopheles mosquitoes when used as a contact insecticide. A long-lasting
      insecticidal net incorporating pyriproxyfen is under development. As wild, host
      seeking females may succeed in blood-feeding at different intervals after initial
      contact with mosquito nets the aim of this study was to determine the effect that
      age and gonotrophic status (nulliparous or parous) and the interval between
      initial pyriproxyfen exposure and blood-feeding has in terms of subsequent
      reduced fecundity and fertility. Anopheles gambiae s.s. were exposed to
      pyriproxyfen LLIN for three minutes in WHO cone bioassays. Four regimens were
      tested with different blood-feeding intervals A-1 hour (nulliparous), B-1 hour
      (parous), C-24h (nulliparous), or D-120h (nulliparous) after pyriproxyfen
      exposure. Mosquito oviposition rate, fecundity and fertility of eggs were
      recorded for several days. All four treatment regimens produced levels of
      mortality similar to unexposed females. The overall reduction in reproductive
      rate of 99.9% for regimen A relative to the untreated net was primarily due to
      oviposition inhibition in exposed females (97%). Pyriproxyfen was equally
      effective against older parous mosquitoes and when blood-feeding was 24h after
      exposure. Regimen D produced a reduction in reproductive rate of 60.1% but this
      was of lesser magnitude than other regimens and was the only regimen that failed
      to reduce fertility of laid eggs, indicating the effects of pyriproxyfen exposure
      on reproduction are to some extent reversible as mosquitoes age. In an area of
      moderate to high mosquito net coverage a host-seeking mosquito is likely to
      contact a treated mosquito net before: (a) penetrating a holed net and blood
      feeding shortly after exposure or, (b) be frustrated by intact nets before
      succeeding in blood-feeding on an unprotected individual the following night.
      Mosquito nets are an appropriate delivery system for pyriproxyfen, based on the
      large reductions in reproductive rate when blood-feeding between 1h and 24h after
      exposure. Combining with a pyrethroid should be an effective approach if
      susceptible mosquitoes are killed and resistant mosquitoes sterilized.

PMID- 26200791
TI  - IASP Awards 2003.

PMID- 26200790
TI  - 'Un'comfortably numb--A prison requiem.

PMID- 26200793
TI  - International Association for Suicide Prevention.

PMID- 26200794
TI  - In an Age of Open Access to Research Policies: Physician and Public Health NGO
      Staff Research Use and Policy Awareness.
AB  - INTRODUCTION: Through funding agency and publisher policies, an increasing
      proportion of the health sciences literature is being made open access. Such an
      increase in access raises questions about the awareness and potential utilization
      of this literature by those working in health fields. METHODS: A sample of
      physicians (N=336) and public health non-governmental organization (NGO) staff
      (N=92) were provided with relatively complete access to the research literature
      indexed in PubMed, as well as access to the point-of-care service UpToDate, for
      up to one year, with their usage monitored through the tracking of web-log data.
      The physicians also participated in a one-month trial of relatively complete or
      limited access. RESULTS: The study found that participants' research interests
      were not satisfied by article abstracts alone nor, in the case of the physicians,
      by a clinical summary service such as UpToDate. On average, a third of the
      physicians viewed research a little more frequently than once a week, while two
      thirds of the public health NGO staff viewed more than three articles a week.
      Those articles were published since the 2008 adoption of the NIH Public Access
      Policy, as well as prior to 2008 and during the maximum 12-month embargo period.
      A portion of the articles in each period was already open access, but complete
      access encouraged a viewing of more research articles. CONCLUSION: Those working
      in health fields will utilize more research in the course of their work as a
      result of (a) increasing open access to research, (b) improving awareness of and
      preparation for this access, and (c) adjusting public and open access policies to
      maximize the extent of potential access, through reduction in embargo periods and
      access to pre-policy literature.

PMID- 26200796
TI  - Dye-sensitized polyoxometalate for visible-light-driven photoelectrochemical
      cells.
AB  - A simple and facile one-step method for the synthesis of an organic dye
      functionalized polyoxometalate (POM) hybrid with visible-light photo-response was
      reported. The POM hybrid was fully characterized via single crystal XRD, powder
      XRD, FTIR and elemental analysis. The reaction of the organic dye with inorganic
      salts gave the dye-functionalized POM (MoBB3), in which the POM cluster was
      formed in situ. The electronic absorption peak of this hybrid was successfully
      extended beyond 680 nm. Photoelectrochemical measurement indicated that MoBB3 was
      photoresponsive under visible-light illumination, suggesting that it is an n-type
      (electron conductive) semiconducting material. This result might offer a method
      for the design of novel organic dye-functionalized POMs for photoelectric
      applications. 

PMID- 26200795
TI  - Probiotic properties of Enterococcus strains isolated from traditional naturally
      fermented cream in China.
AB  - The purpose of this study was to evaluate the probiotic properties of
      Enterococcus strains isolated from traditional naturally fermented cream in
      China. Four Enterococcus isolates showed high cholesterol removal ability in
      media were identified as Enterococcus durans (KLDS 6.0930 and 6.0933) and
      Enterococcus faecalis (KLDS 6.0934 and 6.0935) by 16S rRNA and pheS gene
      sequences, respectively, and selected for further evaluation. In order to assess
      the probiotic potential and safety of these strains, the property of four
      Enterococcus strains were examined, including acid and bile tolerance, adherence
      to Caco-2 cells and antibiotics susceptibility. All four strains showed potential
      cholesterol assimilation, de-conjugation of bile salts and/or cholesterol
      degradation to remove cholesterol in vitro. In addition, the potential effect of
      E. durans KLDS 6.0930 on serum cholesterol levels was evaluated in Sprague-Dawley
      rats. After 4 weeks administration, compared with rats fed a high-cholesterol
      diet without lactic acid bacteria supplementation, there was a significant (P <
      0.05) decrease in the total cholesterol and low-density lipoprotein cholesterol
      levels in the serum of rats treated with KLDS 6.0930. Furthermore, total bile
      acid level in the feces was significantly (P < 0.05) increased after KLDS 6.0930
      administration. These observations suggested that the strain E. durans KLDS
      6.0930 may be used in the future as a good candidate for lowering human serum
      cholesterol levels.

PMID- 26200797
TI  - Scan Rate Dependent Spin Crossover Iron(II) Complex with Two Different
      Relaxations and Thermal Hysteresis fac-[Fe(II)(HL(n-Pr))3]Cl.PF6 (HL(n-Pr) = 2
      Methylimidazol-4-yl-methylideneamino-n-propyl).
AB  - Solvent-free spin crossover Fe(II) complex fac-[Fe(II)(HL(n-Pr))3]Cl.PF6 was
      prepared, where HL(n-Pr) denotes 2-methylimidazol-4-yl-methylideneamino-n-propyl.
      The magnetic susceptibility measurements at scan rate of 0.5 K min(-1) showed two
      successive spin transition processes consisting of the first spin transition T1
      centered at 122 K (T1? = 127.1 K, T1? = 115.8 K) and the second spin transition
      T2 centered at ca. 105 K (T2? = 115.8 K, T2? = 97.2 K). The magnetic
      susceptibility measurements at the scan rate of 2.0, 1.0, 0.5, 0.25, and 0.1 K
      min(-1) showed two scan speed dependent spin transitions, while the Mossbauer
      spectra detected only the first spin transition T1. The crystal structures were
      determined at 160, 143, 120, 110, 95 K in the cooling mode, and 110, 120, and 130
      K in the warming mode so as to follow the spin transition process of high-spin HS
      -> HS(T1) -> HS(T2) -> low-spin LS -> LS(T2) -> LS(T1) -> HS. The crystal
      structures at all temperatures have a triclinic space group P1 with Z = 2. The
      complex-cation has an octahedral N6 coordination geometry with three bidentate
      ligands and assume a facial-isomer with Delta- and Lambda-enantimorphs. Three
      imidazole groups of fac-[Fe(II)(HL(n-Pr))3](2+) are hydrogen-bonded to three Cl(
      ) ions. The 3:3 NH(imidazole)...Cl(-) hydrogen-bonds form a stepwise ladder
      assembly structure, which is maintained during the spin transition process. The
      spin transition process is related to the structural changes of the FeN6
      coordination environment, the order-disorder of PF6(-) anion, and the
      conformation change of n-propyl groups. The Fe-N bond distance in the HS state is
      longer by 0.2 A than that in the LS state. Disorder of PF6(-) anion is not
      observed in the LS state but in the HS state. The conformational changes of n
      propyl groups are found in the spin transition processes except for HS -> HS(T1) 
      > HS(T2). 

PMID- 26200798
TI  - Prospective cohort feasibility study of a transdiagnostic group intervention for
      common mental health problems: The Take Control Course.
AB  - OBJECTIVES: While transdiagnostic psychological treatments appear to be
      promising, they require greater empirical support. Further, a number of available
      transdiagnostic treatments are targeted at clients with a specific category of
      disorder, such as clients with anxiety disorders. This study is a preliminary
      examination of the effectiveness, feasibility, and acceptability of a new
      transdiagnostic six-session group-based intervention (Take Control Course; TCC)
      predominantly aimed at clients within primary care. The group is aimed at a broad
      range of clients; it is derived from an integrative transdiagnostic theory, which
      specifies mechanisms of psychopathology across disorders. Briefer interventions
      are gaining an increasing evidence base, and this study seeks to compare the TCC
      to an established brief intervention within primary care. DESIGN: Prospective
      cohort study comparing two active psychological treatments. METHODS: Take Control
      Course group (n = 66) was compared to a non-randomized control group of clients
      accessing individual low-intensity interventions (n = 43) using random-effect
      regression models. Primary outcomes were depression and anxiety scores;
      additional outcomes included social and other functioning. RESULTS: For the TCC
      group, changes on all pre-post outcomes were significant with moderate effect
      sizes. The between-group differences were not significant. CONCLUSIONS: Results
      show potential for TCC to be an effective intervention, but further work is
      required to validate these findings in a more rigorous, randomized study.
      PRACTITIONER POINTS: Transdiagnostic understandings of psychological distress may
      inform pragmatic and effective treatments that can be offered to a broad range of
      clients. This study describes a transdiagnostic intervention (TCC) that targets
      maintenance processes common across disorders, and presents initial outcome data.
      The TCC was found to reduce pre-post scores on measures of anxiety and
      depression.

PMID- 26200799
TI  - NLRP3 inflammasome is expressed by astrocytes in the SOD1 mouse model of ALS and
      in human sporadic ALS patients.
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of
      motoneurons in the cerebral cortex, brainstem and spinal cord. Neuroinflammation
      plays an important role in the pathogenesis of ALS and involves the activation of
      microglia and astrocytes. Intracellular inflammasome complexes are part of the
      innate immunity as they sense and execute host inflammatory responses. The best
      characterized component is the NLRP3 inflammasome comprised of the NLR protein
      NLRP3, the adaptor ASC and pro-caspase 1. The NLRP3 inflammasome is critical for
      the activation of caspase 1 and the processing and release of IL1beta and IL18.
      In this study, we investigated the expression, activation and co-localization of
      the NLRP3 inflammasome in the spinal cord of male SOD1(G93A) mice carrying a
      mutant human superoxide dismutase 1 (SOD1) variant and regarded as an animal
      model for ALS as well as in post-mortem tissue of ALS patients. NLRP3 and its
      molecular components as well as IL1beta were already detectable in SOD1 mice at a
      pre-symptomatic stage after 9 weeks and further increased in 14 week old animals.
      Spinal cord astrocytes were identified as the major cell type expressing NLRP3
      components. In human ALS tissue, we also found increased NLRP3, ASC, IL18 and
      active caspase 1 levels compared to control patients. Our findings suggest that
      astroglial NLRP3 inflammasome complexes are critically involved in
      neuroinflammation in ALS.

PMID- 26200800
TI  - Neutral Models of Microbiome Evolution.
AB  - There has been an explosion of research on host-associated microbial communities
      (i.e.,microbiomes). Much of this research has focused on surveys of microbial
      diversities across a variety of host species, including humans, with a view to
      understanding how these microbiomes are distributed across space and time, and
      how they correlate with host health, disease, phenotype, physiology and ecology.
      Fewer studies have focused on how these microbiomes may have evolved. In this
      paper, we develop an agent-based framework to study the dynamics of microbiome
      evolution. Our framework incorporates neutral models of how hosts acquire their
      microbiomes, and how the environmental microbial community that is available to
      the hosts is assembled. Most importantly, our framework also incorporates a
      Wright-Fisher genealogical model of hosts, so that the dynamics of microbiome
      evolution is studied on an evolutionary timescale. Our results indicate that the
      extent of parental contribution to microbial availability from one generation to
      the next significantly impacts the diversity of microbiomes: the greater the
      parental contribution, the less diverse the microbiomes. In contrast, even when
      there is only a very small contribution from a constant environmental pool,
      microbial communities can remain highly diverse. Finally, we show that our models
      may be used to construct hypotheses about the types of processes that operate to
      assemble microbiomes over evolutionary time. 

PMID- 26200801
TI  - Rapidly progressive interstitial lung fibrosis in a patient with amyopathic
      dermatomyositis and anti-MDA5 antibodies.

PMID- 26200802
TI  - Relational Memory as a Possible Neurocognitive Marker of Schizophrenia.

PMID- 26200803
TI  - Effect of oral diclofenac intake on faecal calprotectin.
AB  - BACKGROUND: NSAIDs are a known source of increased faecal calprotectin (FC)
      levels. Currently, there is a lack of knowledge about how long it takes for an
      increased FC level to return to normal after NSAID intake. OBJECTIVE: The aim was
      to investigate how oral diclofenac intake affects FC levels and assess how long
      it takes for an increased FC level to return to normal after oral diclofenac
      intake. MATERIAL AND METHODS: Thirty healthy volunteers received diclofenac 50 mg
      three times daily for 14 days. Participants provided a stool sample on Days 0, 2,
      4, 7, 14 during intake and Days 17, 21, 28 after discontinuation. FC levels were
      then followed at 7-day intervals until normalization. RESULTS: During diclofenac
      intake, eight participants (27%) had FC levels exceeding the upper limit of
      normal (median, 76 MUg/g; range, 60-958 MUg/g), corresponding to 8.3% of
      measurements. FC was not constantly increased and became normal in most
      participants during diclofenac intake. FC levels were on average significantly
      higher during intake (M = 9.5, interquartile range (IQR) = 13.4) than on baseline
      (M = 7.5, IQR = 0.0), p = 0.003. After discontinuation, two participants had
      increased FC on Days 17 and 21, respectively. No significant differences in FC
      levels were found between baseline and measurements after discontinuation. Two
      weeks after discontinuation, all participants had normal FC levels. CONCLUSIONS:
      Short-term oral diclofenac intake is associated with increased FC levels.
      However, the likelihood of an increased test result is low. Our results suggest
      that 2 weeks of diclofenac withdrawal is sufficient to get an uninfluenced FC
      test result.

PMID- 26200804
TI  - Lower Extremity Proximal Muscle Function and Dyspnea in Older Persons.
AB  - OBJECTIVES: To evaluate the association between performance on a single chair
      stand and moderate to severe exertional dyspnea. DESIGN: Cross-sectional.
      SETTING: Cardiovascular Health Study. PARTICIPANTS: Community-dwelling
      individuals aged 65 and older (N = 4,413; mean age 72.6; female, n = 2,518
      (57.1%); nonwhite, n = 199 (4.5%); obese, n = 788 (17.9%); history of smoking, n
      = 2,410 (54.6%)). MEASUREMENTS: Performance on single chair stand (poor (unable
      to rise without arm use) vs normal (able to rise without arm use)), moderate to
      severe exertional dyspnea (American Thoracic Society grade >=2), age, sex,
      ethnicity, obesity, smoking, frailty status (Fried-defined nonfrail, prefrail,
      frail), high cardiopulmonary risk (composite of cardiopulmonary diseases and
      diabetes mellitus), spirometric impairment, arthritis, depression, stroke, and
      kidney disease. RESULTS: Poor performance on the single chair stand was
      established in 369 (8.4%) and moderate to severe exertional dyspnea in 773
      (17.5%). Prefrail status was established in 2,210 (50.1%), frail status in 360
      (8.2%), arthritis in 2,241 (51.4%), high cardiopulmonary risk in 2,469 (55.9%),
      spirometric impairment in 1,076 (24.4%), kidney disease in 111 (2.5%), depression
      in 107 (2.4%), and stroke in 93 (2.1%). In multivariable regression models, poor
      performance on the single chair stand was associated with moderate to severe
      exertional dyspnea (unadjusted odds ratio (OR) = 3.48, 95% confidence interval
      (CI) = 2.78-4.36; adjusted OR = 1.85, 95% CI = 1.41-2.41). CONCLUSION: Poor
      performance on a single chair stand was associated with an adjusted 85% greater
      likelihood of moderate to severe exertional dyspnea than normal performance.
      These results suggest that reduced proximal muscle function of the lower
      extremities is associated with moderate to severe exertional dyspnea, even after
      adjusting for multiple confounders.

PMID- 26200805
TI  - Establishing the role of detoxifying enzymes in field-evolved resistance to
      various insecticides in the brown planthopper (Nilaparvata lugens) in South
      India.
AB  - The brown planthopper (BPH), Nilaparvata lugens (Stal), is one of the major pests
      of rice throughout Asia. Extensive use of insecticides for suppressing N. lugens
      has resulted in the development of insecticide resistance leading to frequent
      control failures in the field. The aim of the present study was to evaluate
      resistance in the field populations of N. lugens from major rice growing states
      of South India to various insecticides. We also determined the activity of
      detoxifying enzymes (esterases [ESTs], glutathione S-transferases [GSTs], and
      mixed-function oxidases [MFOs]). Moderate levels of resistance were detected in
      the field populations to acephate, thiamethoxam and buprofezin (resistance
      factors 1.05-20.92 fold, 4.52-14.99 fold, and 1.00-18.09 fold, respectively) as
      compared with susceptible strain while there were low levels of resistance to
      imidacloprid (resistance factor 1.23-6.70 fold) and complete sensitivity to
      etofenoprox (resistance factor 1.05-1.66 fold). EST activities in the field
      populations were 1.06 to 3.09 times higher than the susceptible strain while for
      GST and MFO the ratios varied from 1.29 to 3.41 and 1.03 to 1.76, respectively.
      The EST activity was found to be correlated to acephate resistance (r = 0.999, P
      >= 0.001). The high selection pressure of organophosphate, neonicotinoid, and
      insect growth regulator (IGR) in the field is likely to be contributing for
      resistance in BPH to multiple insecticides, leading to control failures. The
      results obtained will be beneficial to IPM recommendations for the use of
      effective insecticides against BPH.

PMID- 26200806
TI  - Elevated levels of peripheral blood CD14(bright) CD16+ and CD14(dim) CD16+
      monocytes may contribute to the development of retinopathy in patients with
      juvenile onset type 1 diabetes.
AB  - The study aimed to analyze the CD14(bright) CD16(+) and CD14(dim) CD16(+)
      monocyte subsets in juvenile-onset complication-free diabetes mellitus type 1 in
      the context of their association with microvascular complications. 61 children
      with type 1 diabetes and 30 healthy individuals were enrolled in a study.
      CD14(bright) CD16(+) and CD14(dim) CD16(+) monocytes were quantified in
      peripheral blood by means of flow cytometry. At the time of sampling blood
      glucose concentration was taken along with biochemical measurement of renal
      function, CRP and glycosylated hemoglobin. The Spearman's correlations were used
      to compare the relationship between CD16(+) monocyte subsets and the clinical
      parameters that can predict the development of microangiopathies. The flow
      cytometric analysis of monocyte subsets in peripheral blood of analyzed subjects
      revealed that the numbers of CD14(bright) CD16(+) and CD14(dim) CD16(+) monocytes
      were significantly higher in patients with type 1 diabetes than in the healthy
      individuals. As to the relationship between CD16(+) monocyte subsets and the
      clinical parameters that can predict development of microangiopathies, it was
      shown that both CD16(+) subsets were associated with increased risk of
      retinopathy development, defined as retinopathy development value. Elevated
      levels of intermediate CD14(bright) CD16(+) and non-classical CD14(dim) CD16(+)
      monocytes predict development of diabetic retinopathy in patients with type 1
      diabetes. 

PMID- 26200807
TI  - Silver-Copper Nanoalloy Catalyst Layer for Bifunctional Air Electrodes in
      Alkaline Media.
AB  - A carbon-free and binder-free catalyst layer composed of a Ag-Cu nanoalloy on Ni
      foam was used as the air cathode in a zinc-air battery for the first time. The Ag
      Cu catalyst was prepared using pulsed laser deposition. The structures of the
      catalysts were found to consist of crystalline Ag-Cu nanoalloy particles with an
      average size of 2.58 nm embedded in amorphous Cu films. As observed in the X-ray
      photoelectron spectra, the Ag 3d core levels shifted to higher binding energies,
      whereas the Cu 2p core levels shifted to lower binding energies, indicating
      alloying of the silver and copper. Rotating disk electrode measurements indicated
      that the oxygen reduction reaction (ORR) proceeded through a four-electron
      pathway on the Ag50Cu50 and Ag90Cu10 nanoalloy catalysts in alkaline solution.
      Moreover, the catalytic activity of Ag50Cu50 in the ORR is more efficient than
      that of Ag90Cu10. By performing charge and discharge cycling measurements, the
      Ag50Cu50 catalyst layer was confirmed to have a maximum power density of
      approximately 86.3 mW cm(-2) and an acceptable cell voltage at 0.863 V for
      current densities up to 100 mA cm(-2) in primary zinc-air batteries. In addition,
      a round-trip efficiency of approximately 50% at a current density of 20 mA cm(-2)
      was also obtained in the test. 

PMID- 26200808
TI  - Development of a dexamethasone intravitreal implant for the treatment of
      noninfectious posterior segment uveitis.
AB  - Uveitis is a group of ocular inflammatory disorders that can lead to severe
      vision loss. Despite advances in anti-inflammatory therapy, many patients are
      resistant to or intolerant of existing treatments. A biodegradable, sustained
      release implant, dexamethasone intravitreal implant 0.7 mg (Ozurdex), has been
      developed to deliver dexamethasone to target tissues in the posterior segment of
      the eye, minimizing systemic drug exposure and limiting side effects. The implant
      releases dexamethasone over a period of up to 6 months as the poly(D,L-lactide-co
      glycolide) polymer matrix of the implant is metabolized to carbon dioxide and
      water. The implant is placed in the vitreous of the eye with a single-use
      applicator in a sutureless, office-based procedure. Treatment with a single
      dexamethasone intravitreal implant in patients with noninfectious intermediate or
      posterior uveitis has been shown to produce significant improvements in
      intraocular inflammation and best-corrected visual acuity with treatment benefit
      sustained for 6 months. Dexamethasone intravitreal implant has also been shown to
      reduce central retinal thickness and improve best-corrected visual acuity in
      patients with macular edema of various etiologies. The implant has been approved
      for treatment of noninfectious uveitis involving the posterior segment, diabetic
      macular edema, and macular edema associated with branch and central retinal vein
      occlusion.

PMID- 26200809
TI  - Organic photovoltaics without p-n junctions: a computational study of
      ferroelectric columnar molecular clusters.
AB  - Structural and electronic properties of ferroelectric columnar clusters
      constructed from benzene-1,3,5-tricarboxylic acid, (B3CA)N, were investigated at
      the Hartree-Fock level. It is shown that B3CA stacks form helix-shaped molecular
      tubes which are stabilized by intermolecular hydrogen bonds. It is furthermore
      shown that the strong electric field generated by the uniaxial alignment of the
      carboxyl groups can split an optically prepared exciton into an electron-hole
      pair and can drive the charge carriers to the opposite ends of the tube. Some
      consequences of the phenomenon for photovoltaic applications are discussed. 

PMID- 26200810
TI  - Magnetic resonance spectroscopy of the brain: a review of physical principles and
      technical methods.
AB  - Magnetic resonance spectroscopy (MRS) provides unique information about the
      neurobiological substrates of brain function in health and disease. However, many
      of the physical principles underlying MRS are distinct from those underlying
      magnetic resonance imaging, and they may not be widely understood by
      neuroscientists new to this methodology. This review describes these physical
      principles and many of the technical methods in current use for MRS experiments.
      A better understanding these principles and methods may help investigators select
      pulse sequences and quantification methods best suited to the aims of their
      research program and avoid pitfalls that can hamper new investigators in this
      field. 

PMID- 26200811
TI  - Capillary electrochromatography-mass spectrometry for the determination of 5
      nitroimidazole antibiotics in urine samples.
AB  - The separation of eight antibiotics belonging to 5-nitroimidazole family was
      carried out by means of CEC coupled with MS. Preliminary experiments were carried
      out with ultraviolet detection in order to select the proper stationary and
      mobile phase. Among the different stationary phases studied (namely Lichrospher
      C18, 5 MUm particle size; Cogent(TM) Bidentate C18, 4.2 MUm; Pinnacle IITM
      Phenyl, 3 MUm; Pinnacle IITM Cyano, 3 MUm), CogentTM Bidentate C18 (4.2 MUm) gave
      the best performance. For CEC-MS coupling, a laboratory assembled liquid-junction
      nano-spray interface was used. In order to achieve a good sensitivity, special
      attention was paid to both optimization of the sheath liquid composition as well
      as selection of the injection mode. Under optimized CEC-ESI-MS conditions, the
      separation was accomplished within 22 min by using a column packed with a mixture
      of Bidentate C18:Lichrospher Silica-60 (5 MUm) 3:1 w/w, an inlet pressure of 11
      bar, a voltage of 15 kV, and a mobile phase composed by 45:10:45 v/v/v
      ACN/MeOH/water containing ammonium acetate (5 mM pH 5). A combined hydrodynamic
      and electrokinetic injection of 8 bar, 15 kV, and 96 s was adopted. The method
      was validated in terms of repeatability and intermediate precision of retention
      times and peak areas, linearity, and LODs and LOQs. RSDs values were <2.9% for
      retention times and <16.1% for peak areas in both intraday and interday
      experiments. LOQ values were between 0.09 and 0.42 MUg/mL for all compounds.
      Finally, the method was applied to the determination of three most employed 5
      nitroimidazole antibiotics (metronidazole, secnidazole, and ternidazole) in
      spiked urine samples, subjected to a SPE procedure. Recovery values in the 67
      103% range were obtained. Furthermore, for the selected antibiotics, CEC-MS(2)
      spectra were obtained providing the unambiguous confirmation of these drugs in
      urine samples. 

PMID- 26200812
TI  - Through a Gender Lens: A View of Gender and Leadership Positions in a Department
      of Medicine.
AB  - BACKGROUND: Despite increasing numbers in academic medicine, women remain
      underrepresented in top leadership positions. The objectives of this study were
      to characterize leadership positions held by department of medicine (DOM) faculty
      at all ranks at one Academic Health Center and to compare leadership positions
      held by male and female faculty. METHODS: This was a cross-sectional survey to
      collect information on all leadership positions from 16 divisions in the DOM at
      the Johns Hopkins University School of Medicine in early 2012, including type of
      position, method used to fill the position, and financial compensation. Chi
      square testing was used to compare leadership position characteristics by rank
      and gender. RESULTS: The study included 474 DOM faculty at the rank of instructor
      or higher; 38% were women. Of the 258 leadership positions identified, 35% were
      held by women. More leadership positions among assistant professors were held by
      women compared with men (56% of positions vs. 44%), with women assistant
      professors more likely to hold a leadership position than men (p=0.03). Numbers
      of women faculty declined at higher ranks, with leadership positions remaining
      proportionate to faculty representation. Most division director positions (88%)
      were held by men, and most leadership positions were compensated (89%) and
      appointed by the DOM chair or a division director (80%). CONCLUSIONS: Leadership
      positions held by women and men were proportionate to faculty representation,
      although the top leadership positions were held almost exclusively by men. While
      female assistant professors were more likely to hold leadership positions than
      male assistant professors, these positions appear to be low status positions and
      it is not clear that they contribute to professional advancement, as few women
      hold the rank of full professor. Effective interventions are needed to address
      the gender disparity in top leadership positions.

PMID- 26200813
TI  - Discovery of Gemilukast (ONO-6950), a Dual CysLT1 and CysLT2 Antagonist As a
      Therapeutic Agent for Asthma.
AB  - An orally active dual CysLT1 and CysLT2 antagonist possessing a distinctive
      structure which consists of triple bond and dicarboxylic acid moieties is
      described. Gemilukast (ONO-6950) was generated via isomerization of the core
      indole and the incorporation of a triple bond into a lead compound. Gemilukast
      exhibited antagonist activities with IC50 values of 1.7 and 25 nM against human
      CysLT1 and human CysLT2, respectively, and potent efficacy at an oral dose of 0.1
      mg/kg given 24 h before LTD4 challenge in a CysLT1-dependent guinea pig asthmatic
      model. In addition, gemilukast dose-dependently reduced LTC4-induced
      bronchoconstriction in both CysLT1- and CysLT2-dependent guinea pig asthmatic
      models, and it reduced antigen-induced constriction of isolated human bronchi.
      Gemilukast is currently being evaluated in phase II trials for the treatment of
      asthma. 

PMID- 26200814
TI  - Temperature-Dependent Henry's Law Constants of Atmospheric Amines.
AB  - There has been growing interest in understanding atmospheric amines in the gas
      phase and their mass transfer to the aqueous phase because of their potential
      roles in cloud chemistry, secondary organic aerosol formation, and the fate of
      atmospheric organics. Temperature-dependent Henry's law constants (KH) of
      atmospheric amines, a key parameter in atmospheric chemical transport models to
      account for mass transfer, are mostly unavailable. In this work, we investigated
      gas-liquid equilibria of five prevalent atmospheric amines, namely 1-propylamine,
      di-n-propylamine, trimethylamine, allylamine, and 4-methylmorpholine using bubble
      column technique. We reported effective KH, intrinsic KH, and gas phase diffusion
      coefficients of these species over a range of temperatures relevant to the lower
      atmosphere for the first time. The measured KH at 298 K and enthalpy of solution
      for 1-propylamine, di-n-propylamine, trimethylamine, allylamine, and 4
      methylmorpholine are 61.4 +/- 4.9 mol L(-1) atm(-1) and -49.0 +/- 4.8 kJ mol(-1);
      14.5 +/- 1.2 mol L(-1) atm(-1) and -72.5 +/- 6.8 kJ mol(-1); 8.9 +/- 0.7 mol L(
      1) atm(-1) and -49.6 +/- 4.7 kJ mol(-1); 103.5 +/- 10.4 mol L(-1) atm(-1) and 
      42.7 +/- 4.3 kJ mol(-1); and 952.2 +/- 114.3 mol L(-1) atm(-1) and -82.7 +/- 9.7
      kJ mol(-1), respectively. In addition, we evaluated amines' characteristic times
      to achieve gas-liquid equilibrium for partitioning between gas and aqueous
      phases. Results show gas-liquid equilibrium can be rapidly established at natural
      cloud droplets surface, but the characteristic times may be extended
      substantially at lower temperatures and pHs. Moreover, our findings imply that
      atmospheric amines are more likely to exist in cloud droplets, and ambient
      temperature, water content, and pH of aerosols play important roles in their
      partitioning. 

PMID- 26200815
TI  - Local Administration of Methylcobalamin and Lidocaine for Acute Ophthalmic
      Herpetic Neuralgia: A Single-Center Randomized Controlled Trial.
AB  - OBJECTIVES: To determine the therapeutic efficacy of combined methylcobalamin and
      lidocaine for acute ophthalmic herpetic neuralgia (AOHN). METHODS: Based on the
      onset, patients with AOHN (n = 98) were randomly allocated into groups A (<= 3
      days) and B (4 to 7 days) and then subdivided into control (A0, B0; received
      intramuscular methylcobalamin in addition to local lidocaine injection) and
      treatment (A1, B1; received local injection of the methylcobalamin and lidocaine
      combination for 14 days) groups. Treatment efficacy was assessed based on rash
      healing time, alteration of pain intensity, and interference with quality of
      life. Multilevel modeling and survival analysis were performed. RESULTS: The time
      (hours) to start and full opening of the affected eye and the time (hours) to
      start and full crusting were significantly reduced in both treatment groups (P <
      0.05 vs. controls). The mean pain scores in A1 (2.6 +/- 0.7) and B1 (1.2 +/- 0.8)
      decreased significantly compared with those in A0 (7.0 +/- 1.7) and B0 (5.6 +/-
      1.9), and the difference between the two therapeutic strategies significantly
      increased over time. The median minimum intervention time was 6 days in B1 and 11
      days in A1. The incidence of postherpetic neuralgia (PHN) was 2.04% at 3 months.
      CONCLUSIONS: Methylcobalamin combined with lidocaine mediated detumescence and
      improved cutaneous healing of the affected area, as well as a significant and
      sustained analgesic effect on AOHN. The incidence of PHN was also significantly
      decreased. Local methylcobalamin intervention within 4 to 7 days of onset may be
      an effective therapeutic option for AOHN.

PMID- 26200816
TI  - Early Hypoparathyroidism Reversibility with Treatment of Riedel's Thyroiditis.
AB  - BACKGROUND: Riedel's thyroiditis (RT) is a rare, fibroinflammatory condition
      which induces gradual thyroid gland destruction and adjacent soft-tissue fibrous
      infiltration. About one- seventh of RT cases are associated with
      hypoparathyroidism, necessitating long-term therapy for symptomatic hypocalcemia.
      The reversibility of the parathyroid hormone deficit has not been fully
      described. PATIENT FINDINGS: A 40-year-old woman with no prior history of thyroid
      disease presented with a six month history of progressive thyroid enlargement
      complicated by worsening dysphagia and positional dyspnea. Her past medical
      history was remarkable only for retroperitoneal fibrosis. Physical examination
      revealed a large, hard, non-mobile goiter. Thyroid indices while maintained on
      levothyroxine were normal, but marked asymptomatic hypocalcemia with an
      inappropriately normal parathyroid hormone level was noted. Thyroid imaging and
      fine needle aspiration were consistent with RT. Isthmectomy and subsequent serial
      corticosteroid and tamoxifen treatment led to rapid symptom improvement. Serum
      calcium and parathyroid hormone levels returned to the reference range within
      three months. SUMMARY: We describe a case of RT in which hypoparathyroidism
      resolved after treatment targeted the mechanical compression and the
      fibroinflammatory milieu of the patient's thyroidal disease. CONCLUSIONS: RT can
      be associated with hypoparathyroidism that is clinically silent at presentation.
      Mechanical decompression of the goiter and immunomodulatory therapy can reverse
      the fibrosclerotic process and lead to rapid recovery of parathyroid gland
      function, as in this patient. However, in most cases hypoparathyroidism is
      persistent and requires continued treatment to prevent symptomatic hypocalcemia.

PMID- 26200817
TI  - Screening women for intimate partner violence in healthcare settings.
AB  - BACKGROUND: Intimate partner violence (IPV) damages individuals, their children,
      communities, and the wider economic and social fabric of society. Some
      governments and professional organisations recommend screening all women for IPV
      rather than asking only women with symptoms (case-finding). Here, we examine the
      evidence for whether screening benefits women and has no deleterious effects.
      OBJECTIVES: To assess the effectiveness of screening for IPV conducted within
      healthcare settings on identification, referral, re-exposure to violence, and
      health outcomes for women, and to determine if screening causes any harm. SEARCH
      METHODS: On 17 February 2015, we searched CENTRAL, Ovid MEDLINE, Embase, CINAHL,
      six other databases, and two trial registers. We also searched the reference
      lists of included articles and the websites of relevant organisations. SELECTION
      CRITERIA: Randomised or quasi-randomised controlled trials assessing the
      effectiveness of IPV screening where healthcare professionals either directly
      screened women face-to-face or were informed of the results of screening
      questionnaires, as compared with usual care (which could include screening that
      did not involve a healthcare professional). DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed the risk of bias in the trials and undertook data
      extraction. For binary outcomes, we calculated a standardised estimation of the
      odds ratio (OR). For continuous data, either a mean difference (MD) or
      standardised mean difference (SMD) was calculated. All are presented with a 95%
      confidence interval (CI). MAIN RESULTS: We included 13 trials that recruited
      14,959 women from diverse healthcare settings (antenatal clinics, women's health
      clinics, emergency departments, primary care) predominantly located in high
      income countries and urban settings. The majority of studies minimised selection
      bias; performance bias was the greatest threat to validity. The overall quality
      of the body of evidence was low to moderate, mainly due to heterogeneity, risk of
      bias, and imprecision.We excluded five of 13 studies from the primary analysis as
      they either did not report identification data, or the way in which they did was
      not consistent with clinical identification by healthcare providers. In the
      remaining eight studies (n = 10,074), screening increased clinical identification
      of victims/survivors (OR 2.95, 95% CI 1.79 to 4.87, moderate quality
      evidence).Subgroup analyses suggested increases in identification in antenatal
      care (OR 4.53, 95% CI 1.82 to 11.27, two studies, n = 663, moderate quality
      evidence); maternal health services (OR 2.36, 95% CI 1.14 to 4.87, one study, n =
      829, moderate quality evidence); and emergency departments (OR 2.72, 95% CI 1.03
      to 7.19, three studies, n = 2608, moderate quality evidence); but not in hospital
      based primary care (OR 1.53, 95% CI 0.79 to 2.94, one study, n = 293, moderate
      quality evidence).Only two studies (n = 1298) measured referrals to domestic
      violence support services following clinical identification. We detected no
      evidence of an effect on referrals (OR 2.24, 95% CI 0.64 to 7.86, low quality
      evidence).Four of 13 studies (n = 2765) investigated prevalence (excluded from
      main analysis as rates were not clinically recorded); detection of IPV did not
      differ between face-to-face screening and computer/written-based assessment (OR
      1.12, 95% CI 0.53 to 2.36, moderate quality evidence).Only two studies measured
      women's experience of violence (three to 18 months after screening) and found no
      evidence that screening decreased IPV.Only one study reported on women's health
      with no differences observable at 18 months.Although no study reported adverse
      effects from screening interventions, harm outcomes were only measured
      immediately afterwards and only one study reported outcomes at three months.There
      was insufficient evidence on which to judge whether screening increases uptake of
      specialist services, and no studies included an economic evaluation. AUTHORS'
      CONCLUSIONS: The evidence shows that screening increases the identification of
      women experiencing IPV in healthcare settings. Overall, however, rates were low
      relative to best estimates of prevalence of IPV in women seeking healthcare.
      Pregnant women in antenatal settings may be more likely to disclose IPV when
      screened, however, rigorous research is needed to confirm this. There was no
      evidence of an effect for other outcomes (referral, re-exposure to violence,
      health measures, lack of harm arising from screening). Thus, while screening
      increases identification, there is insufficient evidence to justify screening in
      healthcare settings. Furthermore, there remains a need for studies comparing
      universal screening to case-finding (with or without advocacy or therapeutic
      interventions) for women's long-term wellbeing in order to inform IPV
      identification policies in healthcare settings.

PMID- 26200818
TI  - Robustness to noise in gene expression evolves despite epistatic constraints in a
      model of gene networks.
AB  - Stochastic noise in gene expression causes variation in the development of
      phenotypes, making such noise a potential target of stabilizing selection. Here,
      we develop a new simulation model of gene networks to study the adaptive
      landscape underlying the evolution of robustness to noise. We find that epistatic
      interactions between the determinants of the expression of a gene and its
      downstream effect impose significant constraints on evolution, but these
      interactions do allow the gradual evolution of increased robustness. Despite
      strong sign epistasis, adaptation rarely proceeds via deleterious intermediate
      steps, but instead occurs primarily through small beneficial mutations. A simple
      mathematical model captures the relevant features of the single-gene fitness
      landscape and explains counterintuitive patterns, such as a correlation between
      the mean and standard deviation of phenotypes. In more complex networks,
      mutations in regulatory regions provide evolutionary pathways to increased
      robustness. These results chart the constraints and possibilities of adaptation
      to reduce expression noise and demonstrate the potential of a novel modeling
      framework for gene networks. 

PMID- 26200819
TI  - Next generation sequencing of sex-specific genes in the livers of obese ZSF1
      rats.
AB  - Type 2 diabetes induces pathophysiological changes in the liver. The aim of this
      study was to identify differently expressed genes in the livers of male and
      female ZSF1 rats (ZDFxSHHF-hybrid, generation F1), a model for type 2 diabetes.
      Gene expression was investigated using next-generation sequencing (NGS). Selected
      candidate genes were verified by real-time PCR in the livers of obese and lean
      rats. 103 sex-different genes, associated to pathways "response to chemical
      stimulus", "lipid metabolism", and "response to organic substance", were
      identified. Male-specific genes were involved in hepatic metabolism,
      detoxification, and secretion, e.g. cytochrome P450 2c11 (Cyp2c11), Cyp4a2,
      glutathione S-transferases mu 2 (Gstm2), and Slc22a8 (organic anion transporter
      3, Oat3). Most female-specific genes were associated to lipid metabolism (e.g.
      glycerol-3-phosphate acyltransferase 1, Gpam) or glycolysis (e.g. glucokinase,
      Gck). Our data suggest the necessity to pay attention to sex- and diabetes
      dependent changes in pre-clinical testing of hepatic metabolized and secreted
      drugs. 

PMID- 26200820
TI  - A comparison of the postoperative pain experience in children with and without
      attention-deficit hyperactivity disorder (ADHD).
AB  - BACKGROUND: Children with attention-deficit hyperactivity disorder (ADHD) may
      experience pain differently compared to other children, yet the evidence is
      equivocal regarding whether pain is heightened or dampened. This prospective
      observational study, therefore, was designed to compare the postoperative pain
      experiences in children with and without ADHD. METHODS: Children aged 7-17 years
      with a diagnosis of ADHD (n = 119) who were scheduled for a surgical procedure
      requiring postoperative pain management and a matched cohort of children without
      ADHD were recruited (n = 122). Postoperative pain scores and analgesic use were
      recorded for 1 week, as was parents' estimate of their child's return to normal
      activity. RESULTS: There were no differences in highest pain scores between
      children with ADHD (3.3 +/- 2.5, 0-10 numerical rating scale) and those without
      (2.8 +/- 1.9). Postoperative opioid use was also similar on day 1 following
      surgery (0.12 +/- 0.3 mg.kg(-1) vs 0.08 mg.kg(-1 ) +/- 0.1 morphine equivalents,
      respectively). Children with ADHD, however, had a significantly longer return to
      normal activity (4.9 +/- 3.8 vs 3.8 +/- 3.0 days; P < 0.05). CONCLUSIONS: Results
      suggest that there were no differences in the postoperative pain experiences of
      children with and without ADHD. However, the observation that children with ADHD
      took longer to return to baseline activity will be important in educating parents
      regarding their child's postoperative experience.

PMID- 26200821
TI  - Ultrasound during the second stage of labour: is it effective to reduce the
      caesarean section rates?

PMID- 26200822
TI  - [Right subclavian artery evaluation during first trimester ultrasound scan].
AB  - PURPOSE: To determine the feasibility of evaluation of the right subclavian
      artery during the first trimester ultrasound scan, as well as to describe the
      technique for its evaluation and, in case of aberrant right subclavian artery
      (ARSA) identification, to determine its association with chromosomal
      abnormalities and/or cardiac malformations and its management. METHODS: A
      prospective study for evaluation of the right subclavian artery during the first
      trimester ultrasound scan (crown-to-rump length between 45 and 84 mm), in all
      consecutive single pregnancies, by a single examiner, using a Voluson E8 system
      (GE Healthcare, Zipf, Austria) with a 2 to 8 MHz RAB 4-8-D transabdominal probe,
      within a short period of time (less than 2 minutes), in a general low risk
      population. Color and/or power Doppler flow mapping was used to classify the
      right subclavian artery as normal or aberrant. Regression analysis with the IBM
      SPSS Statistics software for Windows, version 20.0 was used to determine the
      significance of the association between failure to examine/classify the right
      subclavian artery and both fetal crown-rump length and maternal body mass index.
      RESULTS: Median maternal age was 30 years (range: 17-43 years) and median
      gestational age at the time of evaluation of the right subclavian artery was 12
      weeks (range: 11-13 weeks). The evaluation of the right subclavian artery was
      successful in 138/176 (78.4%) of the cases. ARSA was diagnosed in a single case
      (0.7%). This fetus with ARSA also presented a hyperechogenic focus on the left
      cardiac ventricle. Fetal echocardiography at 16 weeks of gestation was performed
      and confirmed ARSA and the hyperechogenic focus. Amniocentesis revealed a normal
      46, XX karyotype. CONCLUSION: ARSA can be identified during a routine first
      trimester ultrasound scan. Our single ARSA case had a normal karyotype and no
      associated cardiac malformations.

PMID- 26200823
TI  - Treatment of low-risk gestational trophoblastic neoplasia comparing biweekly
      eight-day Methotrexate with folinic acid versus bolus-dose Actinomycin-D, among
      Brazilian women.
AB  - PURPOSE: To compare two single-agent chemotherapy (ChT) regimens evaluating, in
      first-line treatment, response and side effects and, in final single-agent
      treatment, the outcomes, among Brazilian patients with low-risk gestational
      trophoblastic neoplasia (GTN), according to International Federation of
      Gynecology and Obstetrics (FIGO) 2002. METHODS: Retrospective analysis of two
      concurrent cohorts with 194 low-risk GTN patients: from 1992 to 2012, as first
      line treatment, 115 patients received 4 intramuscular doses of methotrexate
      alternated with 4 oral doses of folinic acid (MTX/FA) repetead every 14 days and,
      since 1996, 79 patients received an endovenous bolus-dose of actinomycin D (Act
      D), biweekly. At GTN diagnosis, patient opinion was taken into consideration when
      defining the initial single-agent ChT regimen, and when there was resistance or
      toxicity to one regimen, the other drug was used preferentially. This study was
      approved by the Irmandade da Santa Casa de Misericordia de Porto Alegre Ethical
      Committee. RESULTS: Both groups were clinically similar (p>0.05). In first-line
      treatments, frequency of complete response was similar (75.7% with MTX/FA and
      67.1% with bolus Act-D); the number of ChT courses -median 3 (range: 1-10) with
      MTX/FA and 2 (range: 1-6) with bolus Act-D - and the time to remission -median 9
      weeks (range: 2-16) with MTX/FA and 10 weeks (range: 2-16) with bolus Act-D) -
      were not different between the groups. In both groups, first-line side effects
      frequency were high but intensity was low; stomatitis was higher with MTX/FA
      (p<0.01) and nausea and vomit with Act-D (p<0.01). Final single-agent ChT
      responses were high in both groups (94.8% with MTX/FA and 83.5% with bolus Act-D;
      p<0.01) and 13% higher in the group initially treated with MTX/FA. Rates of
      hysterectomy and of GTN recurrence were low and similar. No patient died due to
      GTN. CONCLUSION: The two regimens had similar first-line ChT response. Final
      single-agent response rates were high and similar in both groups but the final
      single-agent remission rate was higher in the MTX/FA group.

PMID- 26200824
TI  - [Comparison of quality of life in women with sexual dysfunction].
AB  - PURPOSE: To investigate the relationship between sexual function and quality of
      life in pregnant women living in two cities of Northeastern Brazil. METHODS: The
      sample consisted of 207 pregnant women. The data were collected through a
      questionnaire containing questions about socio-demographic, gynecological and
      obstetrical data, body and sexual knowledge. Quality of life was assessed by
      applying the Ferrans & Powers Quality of Life Index (QLI Ferrans and Power).
      Sexual function was assessed using the Female Sexual Function Index (IFSF). Data
      were statistically analyzed using the Shapiro-Wilk, Mann-Whitney and Wilcoxon
      tests. RESULTS: The pregnant women studied had a median age of 30 years (quartile
      26-33 years) and were approximately at the 26th gestational week. A significant
      decrease in the monthly frequency of sexual relations of the couple was observed,
      with a median of 12 to 4 times per month (Z=-10.56; p<0.001). Sexual dysfunction
      was detected in 35.7% of the pregnant women studied, whose quality of life was
      lower when compared to women with unchanged sexual function (Z=-2.9; p=0.004).
      CONCLUSION: The results of this study show that sexual dysfunction negatively
      affected the quality of life of pregnant women, and this should be an important
      aspect for review during prenatal consultations.

PMID- 26200825
TI  - [Ovarian function in systemic lupus erythematosus patients undergoing the use of
      cyclophosphamide in two major rheumatologic care centers in Curitiba, Parana
      State].
AB  - PURPOSE: To evaluate the ovarian response after cyclophosphamide use (CPM) in
      patients with systemic lupus erythematosus (SLE) and to correlate the age and
      cumulative dose findings with changes in menstrual cycle and/or progression to
      ovarian failure (OF). METHODS: This was a cross-sectional, retrospective study of
      50 patients with a diagnosis of SLE who used CFM with a clinical follow-up of at
      least 1 year. Included were patients aged 12-40 years, who had undergone
      chemotherapy for SLE control and who had regular menstrual cycles before the
      beginning of CPM treatment. Patients who discontinued follow-up, who were
      followed up for less than one year or who had irregular/absent menses before the
      beginning of CPM treatment were excluded. All women studied were submitted to an
      interview and a questionnaire containing questions about the pattern of the
      menstrual cycle before and after therapy, and about the gestational periods and
      contraception. We asked if the patients had been instructed about the side
      effects and consequences of CFM. Statistical analysis was performed using the
      Student t-test and the Mann Whitney, chi2 and nonparametric Kolmogorov-Smirnov
      tests. RESULTS: The mean age of the patients included in the study was 30.8 years
      and the mean age at the time of use of CPM was 25.3 years. After CFM, 24% of
      patients stopped menstruating, 28% returned to regular cycles and 48% continued
      to have irregular cycles. It was found that the patients who developed OF had
      longer disease duration (12.3 years) than those who did not develop it (8.9
      years). Thirteen patients became spontaneously pregnant after CFM; however, 66%
      progressed to abortion. The mean age of the patients who used CFM and developed
      OF was 28.1 years. Amenorrhea occurred in 50% of those aged 31-40 years, in 22.2%
      of those aged 21-30 years and in 7.7% of those aged 12-20 years. Our study showed
      no statistical correlation between cumulative dose and OF, although cumulative
      doses greater than 11 grams tended to promote some type of menstrual
      irregularity. CONCLUSION: SLE disease duration, age at the time of treatment and
      the highest cumulative doses are important predictors of OF after therapy with
      CFM. Pregnancy in lupus patients is more likely to evolve with abortion after the
      use of chemotherapy. It was seen that a small proportion of patients were aware
      of all the implications of the drug. Therefore, additional studies should be
      conducted for further knowledge and awareness of the importance of contraception
      and the preservation of ovarian tissue on the part of the medical community.

PMID- 26200826
TI  - [Assessment of functional fitness through the set of AAHPERD tests in women after
      menopause: Is there a decline between the fifth and sixth decades of life?].
AB  - PURPOSE: to analize the level of functional fitness of a group of postmenopausal
      women in the city of Presidente Prudente using the set of functional fitness
      tests of the American Alliance for Health, Physical Education, Recreation and
      Dance and to check whether there are differences between groups of women in the
      fifth and sixth decade of life. METHODS: This was a cross-sectional study
      conducted on 175 postmenopausal women (follicle stimulating hormone level>26.72
      mIU/L) in the city of Presidente Prudente in 2013. The inclusion criteria were
      not being part of any type of systematic motor intervention for at least six
      months before the collection of research data; absence of motor or cognitive
      impairment that would prevent the evaluation protocols, and absence of chronic or
      degenerative disease, musculoskeletal injury or comorbidity that could prevent or
      limit the evaluations. The women were evaluated by the same trained examiners.
      The 50 to 59 year group showed a mean age of 55.3 +/- 4.5 years, mean FSH values
      of 53.5 +/- 21.1 mIU/mL, mean coordination of 11.4 +/- 2.2 seconds, mean strength
      of 20.1 +/- 3.9 repetitions, mean flexibility of 51.7 +/- 11.8 cm, mean 23.2 +/-
      2.8 seconds agility and mean aerobic resistance of 500 +/- 43/2. The 60 to 69
      year group had a mean age of 65.1 +/- 4.1 years with FSH 54.9 +/- 15.9, 11.6 +/-
      2.6 seconds coordination, strength 20.3 +/- 4.7 repetitions, 54.6 +/- 11.2 cm
      flexibility, agility 24.7 +/- 4.3 seconds, and aerobic resistance of 508 +/- 51
      seconds. CONCLUSION: It was possible to analyze the functional fitness of
      postmenopausal women through the set of the American Alliance testing for Health,
      Physical Education, Recreation and Dance with no significant differences between
      groups for the variables strength, flexibility, aerobic capacity and
      coordination, and with only the speed variable showing significant differences.
      We recommend further studies seeking to formulate normative values for the
      population in question.

PMID- 26200827
TI  - Gene expression profile of ABC transporters and cytotoxic effect of ibuprofen and
      acetaminophen in an epithelial ovarian cancer cell line in vitro.
AB  - PURPOSES: To determine the basic expression of ABC transporters in an epithelial
      ovarian cancer cell line, and to investigate whether low concentrations of
      acetaminophen and ibuprofen inhibited the growth of this cell line in vitro.
      METHODS: TOV-21 G cells were exposed to different concentrations of acetaminophen
      (1.5 to 15 MUg/mL) and ibuprofen (2.0 to 20 MUg/mL) for 24 to 48 hours. The
      cellular growth was assessed using a cell viability assay. Cellular morphology
      was determined by fluorescence microscopy. The gene expression profile of ABC
      transporters was determined by assessing a panel including 42 genes of the ABC
      transporter superfamily. RESULTS: We observed a significant decrease in TOV-21 G
      cell growth after exposure to 15 MUg/mL of acetaminophen for 24 (p=0.02) and 48
      hours (p=0.01), or to 20 MUg/mL of ibuprofen for 48 hours (p=0.04). Assessing the
      morphology of TOV-21 G cells did not reveal evidence of extensive apoptosis. TOV
      21 G cells had a reduced expression of the genes ABCA1, ABCC3, ABCC4, ABCD3,
      ABCD4 and ABCE1 within the ABC transporter superfamily. CONCLUSIONS: This study
      provides in vitro evidence of inhibitory effects of growth in therapeutic
      concentrations of acetaminophen and ibuprofen on TOV-21 G cells. Additionally,
      TOV-21 G cells presented a reduced expression of the ABCA1, ABCC3, ABCC4, ABCD3,
      ABCD4 and ABCE1 transporters.

PMID- 26200828
TI  - [Beta thalassemia major and pregnancy during adolescence: report of two cases].
AB  - Beta thalassemia major is a rare hereditary blood disease in which impaired
      synthesis of beta globin chains causes severe anemia. Medical treatment consists
      of chronic blood transfusions and iron chelation. We describe two cases of
      adolescents with beta thalassemia major with unplanned pregnancies and late onset
      of prenatal care. One had worsening of anemia with increased transfusional
      requirement, fetal growth restriction, and placental senescence. The other was
      also diagnosed with hypothyroidism and low maternal weight, and was admitted
      twice during pregnancy due to dengue shock syndrome and influenza H1N1-associated
      respiratory infection. She also developed fetal growth restriction and underwent
      vaginal delivery at term complicated by uterine hypotonia. Both patients required
      blood transfusions after birth and chose medroxyprogesterone as a contraceptive
      method afterwards. This report highlights the importance of medical advice on
      contraceptive methods for these women and the role of a specialized prenatal
      follow-up in association with a hematologist. 

PMID- 26200829
TI  - Association of Interleukin-1 Gene Single Nucleotide Polymorphisms with
      Keratoconus in Chinese Han Population.
AB  - PURPOSE: To investigate whether interleukin-1 alpha (IL1A) and interleukin-1 beta
      (IL1B) polymorphisms are associated with keratoconus (KC) in unrelated Chinese
      Han patients. METHODS: The IL1A (rs2071376) and IL1B (rs1143627, rs16944)
      polymorphisms were genotyped in 115 unrelated Chinese Han KC patients and 101
      healthy Chinese Han volunteers with the Sequenom MassARRAY RS1000. Sequenom Typer
      4.0 software, PLINK 1.07, Haploview 4.0 software platform were used to analyze
      the allelic variants of IL1A and IL1B genes, and their association with KC risk
      factors were assessed. RESULTS: Among the variants, the three SNPs (rs2071376 in
      IL1A, rs1143627 and rs16944 in the promoter region of IL1B) were different
      between the two groups. The A allele of rs2071376 (A > C, p = 0.017, OR = 1.968,
      95% C.I. 1.313-3.425), the C allele of rs1143627 (C > T, p < 0.001, OR = 2.864,
      95% C.I. 1.631-4.968) and the A allele of rs16944 (A > G, p = 0.002, OR = 2.401,
      95% C.I. 1.396-4.161) were associated with a increased risk of KC in Chinese Han
      patients. This study showed that rs2071376, rs1143627 and rs16944 had significant
      differences in associations between KC patients and the control group when
      different genotypes were analyzed in three models (dominant, recessive, and
      additive). In the haplotype analysis, the two single nucleotide polymorphisms
      (SNPs), rs1143627 and rs16944 showed strong linkage disequilibrium. In addition,
      Haplotype "ACA" was found to be associated with a higher risk of developing KC
      (OR = 12.91, p < 0.001). CONCLUSION: Keratocyte apoptosis is an initiating event
      in the pathogenesis of KC which could be induced by the altered levels of IL1
      gene. These findings confirmed that polymorphisms in IL1 genes were associated
      with risk of KC in the Chinese Han population, which help us to gain insight into
      the pathogenesis of KC.

PMID- 26200830
TI  - Biotransformation of phloretin by amylosucrase yields three novel dihydrochalcone
      glucosides.
AB  - Glycosylation is one of the most important tailoring reactions for natural
      products. It typically exerts profound direct or indirect effects on their
      biological activity. The dihydrochalcone phloretin and its known sugar
      derivatives, particularly phlori(d)zin, have been shown to influence various
      cellular processes. We found that a non-Leloir glycosyltransferase, amylosucrase
      from Neisseria polysaccharea, is an excellent catalyst for the stereospecific
      glucosylation of phloretin at the 4' position. Three novel phloretin derivatives
      were obtained, the first ones in which the sugar-aglycone bond possesses the
      configuration. A first biological characterization in a cell viability assay
      showed that each sugar attachment reduced the compound toxicity approximately two
      fold. 

PMID- 26200832
TI  - Complete genome sequence of Deinococcus soli N5(T), a gamma-radiation- resistant
      bacterium isolated from rice field in South Korea.
AB  - A Gram-negative, non-motile and short-rod shaped and gamma-radiation-resistant
      bacterium Deinococcus soli N5(T), isolated from a rice field soil in South Korea.
      The complete genome of D. soli N5(T) consists of a chromosome (3,236,984bp). The
      key enzymes for the central DNA repair mechanisms were present in the genome. The
      enzyme coding genes has been identified which is involving in the nucleotide
      excision repair (NER) pathway. The gene cluster in the genome sequence suggest
      that the D. soli N5(T) use (NER) pathways for efficient removal of pyrimidine
      dimers that are the most abundant type of UV- induced damage. 

PMID- 26200831
TI  - Highly efficient enrichment of porcine cells with deletions induced by
      CRISPR/Cas9 using dual fluorescence selection.
AB  - Production of nuclear donor cells with a high percentage of desired modifications
      is a critical step in the successful generation of genetically modified pigs
      through somatic cell nuclear transfer (SCNT). The CRISPR/Cas9 system has been
      used for efficient modification of the nuclear DNA in eukaryotic cells, including
      porcine cells. However, in vitro modified cells are often phenotypically
      indistinguishable from unmodified cells, hampering their enrichment. Here we
      investigate a dual fluorescence selection system for the efficient enrichment of
      porcine embryonic fibroblasts (PEFs) with CRISPR/Cas9-induced chromosomal
      deletions. Enrichment of cells with 170 bp deletions reached a frequency of 74%,
      whilst enrichment of cells with a larger 5 kb deletions achieved a frequency of
      46%. This demonstrates the utility of a dual fluorescence reporter as an
      attractive tool for improving the efficiency of generating genome edited pigs.

PMID- 26200833
TI  - Rescuing chemotaxis of the anticancer agent Salmonella enterica serovar
      Typhimurium VNP20009.
AB  - The role of chemotaxis and motility in Salmonella enterica serovar Typhimurium
      tumor colonization remains unclear. We determined through swim plate assays that
      the well-established anticancer agent S. Typhimurium VNP20009 is deficient in
      chemotaxis, and that this phenotype is suppressible. Through genome sequencing,
      we revealed that VNP20009 and four selected suppressor mutants had a single
      nucleotide polymorphism (SNP) in cheY causing a mutation in the conserved proline
      residue at position 110. CheY is the response regulator that interacts with the
      flagellar motor-switch complex and modulates rotational bias. The four suppressor
      mutants additionally carried non-synonymous SNPs in fliM encoding a flagellar
      switch protein. The CheY-P110S mutation in VNP20009 likely rendered the protein
      unable to interact with FliM, a phenotype that could be suppressed by mutations
      in FliM. We replaced the mutated cheY in VNP20009 with the wild-type copy and
      chemotaxis was partially restored. The swim ring of the rescued strain, VNP20009
      cheY(+), was 46% the size of the parental strain 14028 swim ring. When tested in
      capillary assays, VNP20009 cheY(+) was 69% efficient in chemotaxis towards the
      attractant aspartate as compared to 14028. Potential reasons for the lack of
      complete restoration and implications for bacterial tumor colonization will be
      discussed. 

PMID- 26200834
TI  - Modeling Canadian Quality Control Test Program for Steroid Hormone Receptors in
      Breast Cancer: Diagnostic Accuracy Study.
AB  - The Canadian Immunohistochemistry Quality Control program monitors clinical
      laboratory performance for estrogen receptor and progesterone receptor tests used
      in breast cancer treatment management in Canada. Current methods assess
      sensitivity and specificity at each time point, compared with a reference
      standard. We investigate alternative performance analysis methods to enhance the
      quality assessment. We used 3 methods of analysis: meta-analysis of sensitivity
      and specificity of each laboratory across all time points; sensitivity and
      specificity at each time point for each laboratory; and fitting models for
      repeated measurements to examine differences between laboratories adjusted by
      test and time point. Results show 88 laboratories participated in quality control
      at up to 13 time points using typically 37 to 54 histology samples. In meta
      analysis across all time points no laboratories have sensitivity or specificity
      below 80%. Current methods, presenting sensitivity and specificity separately for
      each run, result in wide 95% confidence intervals, typically spanning 15% to 30%.
      Models of a single diagnostic outcome demonstrated that 82% to 100% of
      laboratories had no difference to reference standard for estrogen receptor and
      75% to 100% for progesterone receptor, with the exception of 1 progesterone
      receptor run. Laboratories with significant differences to reference standard
      identified with Generalized Estimating Equation modeling also have reduced
      performance by meta-analysis across all time points. The Canadian
      Immunohistochemistry Quality Control program has a good design, and with this
      modeling approach has sufficient precision to measure performance at each time
      point and allow laboratories with a significantly lower performance to be
      targeted for advice.

PMID- 26200835
TI  - Rational Manual and Automated Scoring Thresholds for the Immunohistochemical
      Detection of TP53 Missense Mutations in Human Breast Carcinomas.
AB  - Missense mutations in TP53 are common in human breast cancer, have been
      associated with worse prognosis, and may predict therapy effect. TP53 missense
      mutations are associated with aberrant accumulation of p53 protein in tumor cell
      nuclei. Previous studies have used relatively arbitrary cutoffs to characterize
      breast tumors as positive for p53 staining by immunohistochemical assays. This
      study aimed to objectively determine optimal thresholds for p53 positivity by
      manual and automated scoring methods using whole tissue sections from the
      Carolina Breast Cancer Study. p53-immunostained slides were available for 564
      breast tumors previously assayed for TP53 mutations. Average nuclear p53 staining
      intensity was manually scored as negative, borderline, weak, moderate, or strong
      and percentage of positive tumor cells was estimated. Automated p53 signal
      intensity was measured using the Aperio nuclear v9 algorithm combined with the
      Genie histology pattern recognition tool and tuned to achieve optimal nuclear
      segmentation. Receiver operating characteristic curve analysis was performed to
      determine optimal cutoffs for average staining intensity and percent cells
      positive to distinguish between tumors with and without a missense mutation.
      Receiver operating characteristic curve analysis demonstrated a threshold of
      moderate average nuclear staining intensity as a good surrogate for TP53 missense
      mutations in both manual (area under the curve=0.87) and automated (area under
      the curve=0.84) scoring systems. Both manual and automated immunohistochemical
      scoring methods predicted missense mutations in breast carcinomas with high
      accuracy. Validation of the automated intensity scoring threshold suggests a role
      for such algorithms in detecting TP53 missense mutations in high throughput
      studies. 

PMID- 26200836
TI  - BRMS1 and HPA as Progression, Clinical Biological Behaviors, and Poor Prognosis
      related Biomarkers for Gallbladder Adenocarcinoma.
AB  - PURPOSE: To study the expression of breast cancer metastasis suppressor 1 (BRMS1)
      and heparanase (HPA) and evaluate their clinicopathologic significance and
      relationship in benign and malignant lesions of the gallbladder. MATERIALS AND
      METHODS: EnVision immunohistochemical method for determining the expression of
      BRMS1 and HPA was used in routinely paraffin-embedded sections of surgical
      resected specimens from gallbladder adenocarcinoma, peritumoral tissues, polyp,
      and chronic cholecystitis. RESULTS: The positive rate of BRMS1 expression was
      significantly lower in gallbladder adenocarcinoma than that in peritumoral
      tissues (P<0.01), polyp (P<0.01), and chronic cholecystitis (P<0.01). The
      positive rate of HPA expression was significantly higher in gallbladder
      adenocarcinoma than that in peritumoral tissues (P<0.01), polyp (P<0.05), and
      chronic cholecystitis (P<0.01). The positive expression of BRMS1 and negative
      expression of HPA were significantly associated with differentiation, lymph node
      metastasis, and invasion of adenocarcinoma (P<0.05 or P<0.01). Unitivariate
      Kaplan-Meier analysis showed that decreased expression of BRMS1 (P=0.008) or
      increased expression of HPA (P=0.016) was associated with decreased overall
      survival. Multivariate Cox regression analysis showed that decreased expression
      of BRMS1 (P=0.011) and/or increased expression of HPA (P=0.019) was an
      independent bad prognostic predictor in gallbladder adenocarcinoma. CONCLUSION:
      The expression of BRMS1 and/or HPA might be closely related to the
      carcinogenesis, clinical biological behaviors, and prognosis of gallbladder
      adenocarcinoma.

PMID- 26200837
TI  - The RANK Pathway in Advanced Breast Cancer: Does Src Play a Role?
AB  - Receptor activator of NF-kappaB (RANK) and its ligand, RANKL, are essential for
      osteoclastogenesis and modulate osteolytic bone metastasis. The RANKL/RANK system
      is also fundamental for mammary gland development and plays a potential role in
      breast carcinogenesis. c-Src, a nonreceptor tyrosine kinase downstream of RANK,
      is overexpressed in most breast cancers and plays a key role in several
      transduction pathways. The aim of the study was to examine the expression of
      these molecules in tissue microarrays constructed from 62 advanced breast cancers
      and 10 breast cancers controls (no metastasis after follow-up). Significantly
      higher levels of RANK and lower levels of RANKL were found in triple-negative (ER
      /PR-/HER2-) tumors when compared with luminal subtypes, whereas their levels in
      the HER2 subtype were quantitatively in between. RANK expression was
      significantly associated with tumor grade/differentiation by multivariate
      analysis. Despite their high expression in bone, neither molecule in primary
      tumors seemed to be related to a bone-seeking phenotype. Rather, they were
      significantly correlated with a brain-metastatic phenotype. RANKL and RANK were
      significantly associated with survival outcomes. Further, Src expression showed a
      significantly positive linear relationship with RANK, suggesting a potential
      mechanism of the RANKL-RANK axis in regulating breast cancer cell differentiation
      and antiapoptosis. Thus, these molecules may be potential therapeutic targets,
      especially in triple-negative tumors, for which the only systemic treatment
      option is cytotoxic chemotherapy.

PMID- 26200838
TI  - Immunohistochemical Detection of NPM1 Mutation in Acute Myeloid Leukemia and its
      Association With Cup-like Nuclear Morphology of Blasts.
AB  - Blasts showing cup-like nuclei in acute myeloid leukemia (AML) have been
      identified in patients with nucleophosmin 1 gene (NPM1) mutation, that is, AML
      with cytoplasmic NPM (NPMc+ AML). We analyzed 100 consecutive cases of AML, and
      defined the cutoff percentages of cup-like blasts in peripheral blood and bone
      marrow aspirate smears that can predict NPMc+ AML. A lower cutoff level of >=10%
      blasts in peripheral blood and >=9% in bone marrow aspirate gave an excellent
      specificity for NPMc+ AML and a positive-predictive value of 90.9% and a negative
      predictive value of 87.6% for NPMc+ AML. Cup-like nuclei were associated with
      higher total leukocyte count, higher blasts percentage, AML-M1 subtype, and human
      leukocyte antigen-DR region negativity. Our results suggest that cup-like nuclei
      represent an important morphologic clue that can predict NPMc+ AML and guide
      toward prioritizing the further workup of AML patients. 

PMID- 26200839
TI  - Significance of p27 Immunostaining in B-Cell Neoplasm.
AB  - P27 is an important cell cycle regulatory protein. Many reports have validated
      the utility of p27 as a prognostic marker in different human cancers and to prove
      its prognostic role in B-cell neoplasm; 80 newly diagnosed B-cell neoplasm
      patients with mean age of 46.6 years recruited from Hematology/Oncology Unit of
      Ain Shams University Hospitals during the period from January 2008 till June 2010
      were studied for their p27 immunostaining results which showed that all cases of
      chronic lymphocytic leukemia (CLL) were positive for p27, whereas all mantly cell
      lymphoma cases were negative for it. There was significantly higher p27
      positivity in CLL cases compared with non-Hodgkin lymphoma and that indolent
      cases showed significantly higher rate of positivity when compared with
      aggressive and highly aggressive cases. So, we can use this marker to
      differentiate CLL and mantly cell lymphoma in cases of confusion.

PMID- 26200840
TI  - Invasive Micropapillary Carcinoma of the Breast: Immunophenotypic Analysis and
      Role of Cell Adhesion Molecules (CD44 and E-Cadherin) in Nodal Metastasis.
AB  - Invasive micropapillary carcinoma is a morphologically distinct subtype of breast
      carcinoma with high frequency of lymph node metastasis. In this study, we
      analyzed clinicopathologic features, immunophenotype, and expression of adhesion
      molecules [CD44 and E-cadherin (E-Cad)] in pure invasive micropapillary carcinoma
      of the breast. All cases had diffuse micropapillary pattern and were grade II
      tumors. Lymphovascular emboli were present in 80% and lymph node tumor deposits
      were seen in 69.2% cases. The cases were classified as; luminal A (11 cases),
      luminal B (8 cases), Her-2-neu overexpressing (4 cases), and triple negative (2
      cases). All cases were positive for luminal cytokeratin (CK)CK8/18, and 2 cases
      showed <10% positivity for CK5/6. Eighteen cases showed loss of CD44 expression
      and 7 cases showed only weak positivity. Seven cases with lymph node metastasis
      showed reexpression of CD44 at metastatic site. Strong to moderate expression of
      E-Cad was observed in all cases and the corresponding nodal metastasis. To
      conclude, the loss of the CD44 expression plays role in lymphovascular permeation
      and metastasis and it can be hypothesized that its reexpression at metastatic
      site may play a role in homing of tumor cells. However, intact E-Cad expression
      could be because of the fact that tumour cells travel as clusters and retain
      their expression of E-Cad. 

PMID- 26200841
TI  - Invasion phenotypes of oral squamous cell carcinoma.
AB  - The invasion signature of tumor cells can strongly affect their metastatic
      behavior; therefore, we aimed to evaluate the different invasion phenotypes of
      oral squamous cell carcinoma (OSCC) and to determine the correlation of these
      markers with neoplastic mode of invasion. A total of 92 OSCCs were graded
      according to the Yamamoto criteria and subjected to immunohistochemistry using
      monoclonal antibodies against E-cadherin, N-cadherin, and podoplanin. Samples
      were grouped into epithelial-mesenchymal transition (EMT), collective-cell
      invasion (CCI), and combined intermediate phenotypes followed by statistical
      analysis. Significant differences were found among the 3 groups (P<0.001),
      between EMT and CCI (P=0.023) and between the combined phenotypes and both EMT
      and CCI, separately (P<0.001). Mode of invasion was significantly associated with
      E-cadherin (P=0.022), but not the other markers. There seems to be a preference
      for OSCCs to migrate by CCI; however, most our samples showed an intermediate
      phenotype between EMT and CCI, which confirm the existence of a spectrum of
      migration signatures that need to be further evaluated in these tumors. 

PMID- 26200842
TI  - Mesenchymal Stem Cells Adopt Lung Cell Phenotype in Normal and Radiation-induced
      Lung Injury Conditions.
AB  - Lung tissue exposure to ionizing irradiation can invariably occur during the
      treatment of a variety of cancers leading to increased risk of radiation-induced
      lung disease (RILD). Mesenchymal stem cells (MSCs) possess the potential to
      differentiate into epithelial cells. However, cell culture methods of primary
      type II pneumocytes are slow and cannot provide a sufficient number of cells to
      regenerate damaged lungs. Moreover, effects of ablative radiation doses on the
      ability of MSCs to differentiate in vitro into lung cells have not been
      investigated yet. Therefore, an in vitro coculture system was used, where MSCs
      were physically separated from dissociated lung tissue obtained from either
      healthy or high ablative doses of 16 or 20 Gy whole thorax irradiated rats.
      Around 10+/-5% and 20+/-3% of cocultured MSCs demonstrated a change into lung
      specific Clara and type II pneumocyte cells when MSCs were cocultured with
      healthy lung tissue. Interestingly, in cocultures with irradiated lung biopsies,
      the percentage of MSCs changed into Clara and type II pneumocytes cells increased
      to 40+/-7% and 50+/-6% at 16 Gy irradiation dose and 30+/-5% and 40+/-8% at 20 Gy
      irradiation dose, respectively. These data suggest that MSCs to lung cell
      differentiation is possible without cell fusion. In addition, 16 and 20 Gy whole
      thorax irradiation doses that can cause varying levels of RILD, induced different
      percentages of MSCs to adopt lung cell phenotype compared with healthy lung
      tissue, providing encouraging outlook for RILD therapeutic intervention for
      ablative radiotherapy prescriptions. 

PMID- 26200843
TI  - Shifting Vaccination Politics--The End of Personal-Belief Exemptions in
      California.

PMID- 26200844
TI  - Are general practitioners well informed about fibromyalgia?
AB  - AIM: Fibromyalgia syndrome (FMS) is a common rheumatologic disorder characterized
      by easy fatigability, widespread musculoskeletal pain and sleep disorder. In
      spite of its high prevalence, general practitioners, as primary care providers,
      seem to have inadequate knowledge about FMS. This study aimed to assess Iranian
      general practitioners' knowledge about FMS and its treatment. METHOD: A detailed
      questionnaire (including items on signs and symptoms, diagnostic criteria and
      treatment) was completed by 190 general practitioners (54.7% male; mean age: 41
      years). Data analysis was performed with SPSS for Windows 15.0 and awareness
      about all aspects of FMS was reported as percentages. RESULTS: About one-third
      (30%) of the participants had seen at least one case of FMS during their
      practice. Most subjects (62.7%) claimed to know 1-6 tender points. Only 3.2% knew
      16-18 points. The common proposed symptoms of FMS were widespread pain (72.6%),
      excessive fatigue (72.6%), weakness (60.5%), sleep disorder (36.3%), anxiety
      (34.7%) and depression (34.2%). Wrong symptoms including elevated erythrocyte
      sedimentation rate and C-reactive protein, arthritis, joint swelling, weight loss
      and abnormal radiologic findings were selected by 27.9%, 18.9%, 14.7%, 12.6% and
      2.1% of the physicians, respectively. Moreover, selective serotonin reuptake
      inhibitors, tricyclic antidepressant and pregabalin were identified as treatment
      options for FMS by, respectively, 45.8%, 22.1% and 15.3% of the participants.
      Finally, 52.1% and 23.7% of the subjects incorrectly considered nonsteroidal anti
      inflammatory drugs and corticosteroids as treatment modalities for FMS.
      CONCLUSION: Iranian general practitioners are not well informed about FMS.
      Therefore, FMS should be specifically integrated in continuing medical education
      programs and undergraduate medical training curriculum.

PMID- 26200845
TI  - Connecting Personality Structure and Dynamics: Towards a More Evidence-Based and
      Clinically Useful Diagnostic Scheme.
AB  - The purpose of this special issue of the Journal of Personality Disorders is to
      promote the integration of personality structure and dynamics towards more
      evidence-based and clinically useful conceptualizations of personality pathology.
      In this article, we describe a contemporary model of personality structure that
      is useful for distinguishing patients from one another and the connections
      between this structure and within-person dynamics that occur across different
      levels of an individual personality, across situations, and within situations. In
      so doing, we connect the personality trait tradition that has tended to emphasize
      stable individual differences with traditions that have tended to focus on the
      more dynamic aspects of interpersonal behavior and emotional experience. We then
      introduce the empirical articles in this special issue within this integrative
      context, in order to demonstrate the value in connecting personality structure to
      dynamics for research and practice. 

PMID- 26200847
TI  - Intrapersonal Variability in Negative Affect as a Moderator of Accuracy and Bias
      in Interpersonal Perception.
AB  - High intrapersonal variability has frequently been found to be related to poor
      personal and interpersonal outcomes. Little research has examined processes by
      which intrapersonal variability influences outcomes. This study explored the
      relation of intrapersonal variability in negative affect (negative affect flux)
      to accuracy and bias in the perception of a romantic partner's quarrelsome
      behavior. A sample of 93 cohabiting couples participated in a study using an
      event-contingent recording (ECR) methodology in which they reported their
      negative affect, quarrelsome behavior, and perception of their partner's
      quarrelsome behavior in interactions with each other during a 20-day period.
      Negative affect flux was operationalized as the within-person standard deviation
      of negative affect scores across couple interactions. Findings suggested that
      participants were both accurate in tracking changes in their partner's
      quarrelsome behavior and biased in assuming their partner's quarrelsome behavior
      mirrored their own quarrelsome behavior. Negative affect flux moderated both
      accuracy and bias of assumed similarity such that participants with higher flux
      manifested both greater tracking accuracy and larger bias of assumed similarity.
      Negative affect flux may be related to enhanced vigilance to close others'
      negative behavior, which may explain higher tracking accuracy and propensity to
      rely on a person's own negative behavior as a means of judging others' negative
      behavior. These processes may augment these individuals' negative interpersonal
      behavior, enhance cycles of negative social interactions, and lead to poor
      intrapersonal and interpersonal outcomes. 

PMID- 26200846
TI  - The Role of Metaperception in Personality Disorders: Do People with Personality
      Problems Know How Others Experience Their Personality?
AB  - Do people with personality problems have insight into how others experience them?
      In a large community sample of adults (N = 641), the authors examined whether
      people with personality disorder (PD) symptoms were aware of how a close
      acquaintance (i.e., a romantic partner, family member, or friend) perceived them
      by measuring participants' metaperceptions and self-perceptions as well as their
      acquaintance's impression of them on Five-Factor Model traits. Compared to people
      with fewer PD symptoms, people with more PD symptoms tended to be less accurate
      and tended to overestimate the negativity of the impressions they made on their
      acquaintance, especially for the traits of extraversion, agreeableness, and
      conscientiousness. Interestingly, these individuals did not necessarily assume
      that their acquaintance perceived them as they perceived themselves; instead,
      poor insight was likely due to their inability to detect or utilize information
      other than their self-perceptions. Implications for the conceptualization,
      measurement, and treatment of PDs are discussed. 

PMID- 26200848
TI  - A Contingency-Oriented Approach to Understanding Borderline Personality Disorder:
      Situational Triggers and Symptoms.
AB  - This article tested a contingency-oriented perspective to examine the dynamic
      relationships between in-the-moment borderline personality disorder (BPD) symptom
      events and in-the-moment triggers. An experience sampling study with 282 adults,
      including 77 participants with BPD, obtained reports of situational triggers and
      BPD symptom events five times daily for 2 weeks. Triggers included being
      rejected, betrayed, abandoned, offended, and disappointed; having one's self
      concept threatened; being in a boring situation; and being alone. BPD was
      associated with increased situational triggers. Multilevel models revealed
      significant within-person associations between situational triggers and BPD
      symptoms for the average participant in the study, with significant individual
      variance in the strength and direction of trigger-symptom contingencies. Most
      trigger-symptom contingencies were stronger for individuals with greater
      borderline symptomatology, suggesting that triggers are meaningfully related to
      BPD. These findings highlight possible proximal mechanisms that maintain BPD and
      help explain the course of a disorder often described as chaotic and
      unpredictable. 

PMID- 26200850
TI  - A Lot Can Happen in a Few Minutes: Examining Dynamic Patterns Within an
      Interaction to Illuminate the Interpersonal Nature of Personality Disorders.
AB  - Although problematic interpersonal tendencies have often been characterized as a
      traitlike excess of a particular interpersonal style, the interpersonal nature of
      personality disorders may have more to do with patterns of variability in
      interpersonal behavior and the relation of this variability to the varying
      behavior of interaction partners. Indeed, problematic interpersonal tendencies
      may often be evident as patterns within even one interaction. A useful
      methodology for examining moment-to-moment patterns within the course of an
      interaction is the computer joystick technique. To illustrate the potential of
      this new approach for studying problematic interpersonal patterns, the authors
      provide joystick-based analyses of the videoed session between Dr. Donald
      Meichenbaum and the client, Richard (Shostrom, 1986a). The authors show how to
      examine the association between concurrent levels of dominance and affiliation
      within a person, patterns of covariation between partners, and the moderation of
      such entrainment patterns. They also discuss how these indices could illuminate
      disordered interpersonal patterns. 

PMID- 26200849
TI  - Daily Interpersonal and Affective Dynamics in Personality Disorder.
AB  - In this naturalistic study, the authors adopt the lens of interpersonal theory to
      examine between- and within-person differences in dynamic processes of daily
      affect and interpersonal behaviors among individuals (N = 101) previously
      diagnosed with personality disorders who completed daily diaries over the course
      of 100 days. Dispositional ratings of interpersonal problems and measures of
      daily stress were used as predictors of daily shifts in interpersonal behavior
      and affect in multilevel models. Results indicate that ~40%-50% of the variance
      in interpersonal behavior and affect is due to daily fluctuations, which are
      modestly related to dispositional measures of interpersonal problems but strongly
      related to daily stress. The findings support conceptions of personality
      disorders as a dynamic form of psychopathology involving the individuals
      interacting with and regulating in response to the contextual features of their
      environment. 

PMID- 26200851
TI  - Reliability, Sensitivity, and Specificity of Case Formulations for Comorbid
      Profiles in Interpersonal Reconstructive Therapy: Addressing Mechanisms of
      Psychopathology.
AB  - Interpersonal Reconstructive Therapy (IRT) case formulations describe
      psychosocial mechanisms of affective and personality pathology in ways that
      enhance the effectiveness of psychotherapy for individuals. With a valid and
      reliable IRT case formulation, a clinician is in a better position to draw upon
      effective techniques to maximize treatment effects. The case formulation and
      treatment models for IRT were described in depth along with the IRT treatment
      model by Benjamin (2003/2006). Data in this report from 93 adult inpatients with
      complex and comorbid presentations suggest that the case formulation is highly
      reliable and unique to individuals, and that symptoms reflect current
      interpersonal stresses linked to early interactions involving forms of hostility
      in relation with attachment figures and corresponding to three basic patterns in
      adulthood: identification (be like him or her), recapitulation (act as you did
      with him or her), and introjection (treat yourself as you were treated). 

PMID- 26200853
TI  - Packaging life: the origin of ion-selective channels.

PMID- 26200852
TI  - Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children
      with Autism.
AB  - Brain arginine vasopressin (AVP) critically regulates normative social behavior
      in mammals, and experimental disruption of the AVP signaling pathway produces
      social impairments in rodent models. We therefore hypothesized that AVP signaling
      deficits may contribute to social impairments in children with autism spectrum
      disorder (ASD). Since blood measures (which are far easier to obtain than brain
      measures) of AVP are most meaningful if they are related to brain AVP activity,
      Study 1 tested the relationship between AVP concentrations in concomitantly
      collected blood and CSF samples from children and adults (N = 28) undergoing
      clinical procedures. Study 2 tested whether blood AVP concentrations: 1) differed
      between children with ASD (N = 57), their ASD discordant siblings (N = 47), and
      neurotypical controls (N = 55); and 2) predicted social functioning (using the
      NEPSY-II Theory of Mind and Affect Recognition tasks and the Social
      Responsiveness Scale) in this large, well-characterized child cohort. Blood AVP
      concentrations significantly and positively predicted CSF AVP concentrations
      (F1,26 = 7.17, r = 0.46, p = 0.0127) in Study 1. In Study 2, blood AVP
      concentrations did not differ between groups or by sex, but significantly and
      positively predicted Theory of Mind performance, specifically in children with
      ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017). Blood AVP
      concentrations can be used: 1) as a surrogate for brain AVP activity in humans;
      and 2) as a robust biomarker of theory of mind ability in children with ASD.
      These findings also suggest that AVP biology may be a promising therapeutic
      target by which to improve social cognition in individuals with ASD. 

PMID- 26200854
TI  - Cell-shape homeostasis in Escherichia coli is driven by growth, division, and
      nucleoid complexity.
AB  - Analysis of recently published high-throughput measurements of wild-type
      Escherichia coli cells growing at a wide range of rates demonstrates that cell
      width W, which is constant at any particular growth rate, is related (with a CV =
      2.4%) to the level of nucleoid complexity, expressed as the amount of DNA in
      genome equivalents that is associated with chromosome terminus (G/terC). The
      relatively constant (CV = 7.3%) aspect ratio of newborn cells (Lb/W) in
      populations growing at different rates indicates existence of cell-shape
      homeostasis. Enlarged W of thymine-limited thyA mutants growing at identical
      rates support the hypothesis that nucleoid complexity actively affects W.
      Nucleoid dynamics is proposed to transmit a primary signal to the peptidoglycan
      synthesizing system through the transertion mechanism, i.e., coupled
      transcription/translation of genes encoding membrane proteins and inserting these
      proteins into the membrane. 

PMID- 26200855
TI  - Mathematical modeling of the heat-shock response in HeLa cells.
AB  - The heat-shock response is a key factor in diverse stress scenarios, ranging from
      hyperthermia to protein folding diseases. However, the complex dynamics of this
      physiological response have eluded mathematical modeling efforts. Although
      several computational models have attempted to characterize the heat-shock
      response, they were unable to model its dynamics across diverse experimental
      datasets. To address this limitation, we mined the literature to obtain a
      compendium of in vitro hyperthermia experiments investigating the heat-shock
      response in HeLa cells. We identified mechanisms previously discussed in the
      experimental literature, such as temperature-dependent transcription,
      translation, and heat-shock factor (HSF) oligomerization, as well as the role of
      heat-shock protein mRNA, and constructed an expanded mathematical model to
      explain the temperature-varying DNA-binding dynamics, the presence of free HSF
      during homeostasis and the initial phase of the heat-shock response, and heat
      shock protein dynamics in the long-term heat-shock response. In addition, our
      model was able to consistently predict the extent of damage produced by different
      combinations of exposure temperatures and durations, which were validated against
      known cellular-response patterns. Our model was also in agreement with
      experiments showing that the number of HSF molecules in a HeLa cell is roughly
      100 times greater than the number of stress-activated heat-shock element sites,
      further confirming the model's ability to reproduce experimental results not used
      in model calibration. Finally, a sensitivity analysis revealed that altering the
      homeostatic concentration of HSF can lead to large changes in the stress response
      without significantly impacting the homeostatic levels of other model components,
      making it an attractive target for intervention. Overall, this model represents a
      step forward in the quantitative understanding of the dynamics of the heat-shock
      response. 

PMID- 26200856
TI  - Maxwell's mixing equation revisited: characteristic impedance equations for
      ellipsoidal cells.
AB  - We derived a series of, to our knowledge, new analytic expressions for the
      characteristic features of the impedance spectra of suspensions of homogeneous
      and single-shell spherical, spheroidal, and ellipsoidal objects, e.g., biological
      cells of the general ellipsoidal shape. In the derivation, we combined the
      Maxwell-Wagner mixing equation with our expression for the Clausius-Mossotti
      factor that had been originally derived to describe AC-electrokinetic effects
      such as dielectrophoresis, electrorotation, and electroorientation. The
      influential radius model was employed because it allows for a separation of the
      geometric and electric problems. For shelled objects, a special axial
      longitudinal element approach leads to a resistor-capacitor model, which can be
      used to simplify the mixing equation. Characteristic equations were derived for
      the plateau levels, peak heights, and characteristic frequencies of the impedance
      as well as the complex specific conductivities and permittivities of suspensions
      of axially and randomly oriented homogeneous and single-shell ellipsoidal
      objects. For membrane-covered spherical objects, most of the limiting cases are
      identical to-or improved with respect to-the known solutions given by researchers
      in the field. The characteristic equations were found to be quite precise
      (largest deviations typically <5% with respect to the full model) when tested
      with parameters relevant to biological cells. They can be used for the
      differentiation of orientation and the electric properties of cell suspensions or
      in the analysis of single cells in microfluidic systems. 

PMID- 26200857
TI  - Characterizing cell adhesion by using micropipette aspiration.
AB  - We have developed a technique to directly quantify cell-substrate adhesion force
      using micropipette aspiration. The micropipette is positioned perpendicular to
      the surface of an adherent cell and a constant-rate aspiration pressure is
      applied. Since the micropipette diameter and the aspiration pressure are our
      control parameters, we have direct knowledge of the aspiration force, whereas the
      cell behavior is monitored either in brightfield or interference reflection
      microscopy. This setup thus allows us to explore a range of geometric parameters,
      such as projected cell area, adhesion area, or pipette size, as well as dynamical
      parameters such as the loading rate. We find that cell detachment is a well
      defined event occurring at a critical aspiration pressure, and that the
      detachment force scales with the cell adhesion area (for a given micropipette
      diameter and loading rate), which defines a critical stress. Taking into account
      the cell adhesion area, intrinsic parameters of the adhesion bonds, and the
      loading rate, a minimal model provides an expression for the critical stress that
      helps rationalize our experimental results. 

PMID- 26200858
TI  - Helicase processivity and not the unwinding velocity exhibits universal increase
      with force.
AB  - Helicases, involved in a number of cellular functions, are motors that
      translocate along single-stranded nucleic acid and couple the motion to unwinding
      double-strands of a duplex nucleic acid. The junction between double- and single
      strands creates a barrier to the movement of the helicase, which can be
      manipulated in vitro by applying mechanical forces directly on the nucleic acid
      strands. Single-molecule experiments have demonstrated that the unwinding
      velocities of some helicases increase dramatically with increase in the external
      force, while others show little response. In contrast, the unwinding processivity
      always increases when the force increases. The differing responses of the
      unwinding velocity and processivity to force have lacked explanation. By
      generalizing a previous model of processive unwinding by helicases, we provide a
      unified framework for understanding the dependence of velocity and processivity
      on force and the nucleic acid sequence. We predict that the sensitivity of
      unwinding processivity to external force is a universal feature that should be
      observed in all helicases. Our prediction is illustrated using T7 and NS3
      helicases as case studies. Interestingly, the increase in unwinding processivity
      with force depends on whether the helicase forces basepair opening by direct
      interaction or if such a disruption occurs spontaneously due to thermal
      fluctuations. Based on the theoretical results, we propose that proteins like
      single-strand binding proteins associated with helicases in the replisome may
      have coevolved with helicases to increase the unwinding processivity even if the
      velocity remains unaffected. 

PMID- 26200859
TI  - Torsional behavior of axonal microtubule bundles.
AB  - Axonal microtubule (MT) bundles crosslinked by microtubule-associated protein
      (MAP) tau are responsible for vital biological functions such as maintaining
      mechanical integrity and shape of the axon as well as facilitating axonal
      transport. Breaking and twisting of MTs have been previously observed in damaged
      undulated axons. Such breaking and twisting of MTs is suggested to cause axonal
      swellings that lead to axonal degeneration, which is known as "diffuse axonal
      injury". In particular, overstretching and torsion of axons can potentially
      damage the axonal cytoskeleton. Following our previous studies on mechanical
      response of axonal MT bundles under uniaxial tension and compression, this work
      seeks to characterize the mechanical behavior of MT bundles under pure torsion as
      well as a combination of torsional and tensile loads using a coarse-grained
      computational model. In the case of pure torsion, a competition between MAP tau
      tensile and MT bending energies is observed. After three turns, a transition
      occurs in the mechanical behavior of the bundle that is characterized by its
      diameter shrinkage. Furthermore, crosslink spacing is shown to considerably
      influence the mechanical response, with larger MAP tau spacing resulting in a
      higher rate of turns. Therefore, MAP tau crosslinking of MT filaments protects
      the bundle from excessive deformation. Simultaneous application of torsion and
      tension on MT bundles is shown to accelerate bundle failure, compared to pure
      tension experiments. MAP tau proteins fail in clusters of 10-100 elements located
      at the discontinuities or the ends of MT filaments. This failure occurs in a
      stepwise fashion, implying gradual accumulation of elastic tensile energy in
      crosslinks followed by rupture. Failure of large groups of interconnecting MAP
      tau proteins leads to detachment of MT filaments from the bundle near
      discontinuities. This study highlights the importance of torsional loading in
      axonal damage after traumatic brain injury. 

PMID- 26200860
TI  - Evaluating the performance of time-gated live-cell microscopy with lanthanide
      probes.
AB  - Probes and biosensors that incorporate luminescent Tb(III) or Eu(III) complexes
      are promising for cellular imaging because time-gated microscopes can detect
      their long-lifetime (approximately milliseconds) emission without interference
      from short-lifetime (approximately nanoseconds) fluorescence background.
      Moreover, the discrete, narrow emission bands of Tb(III) complexes make them
      uniquely suited for multiplexed imaging applications because they can serve as
      Forster resonance energy transfer (FRET) donors to two or more differently
      colored acceptors. However, lanthanide complexes have low photon emission rates
      that can limit the image signal/noise ratio, which has a square-root dependence
      on photon counts. This work describes the performance of a wide-field, time-gated
      microscope with respect to its ability to image Tb(III) luminescence and Tb(III)
      mediated FRET in cultured mammalian cells. The system employed a UV-emitting LED
      for low-power, pulsed excitation and an intensified CCD camera for gated
      detection. Exposure times of ~1 s were needed to collect 5-25 photons per pixel
      from cells that contained micromolar concentrations of a Tb(III) complex. The
      observed photon counts matched those predicted by a theoretical model that
      incorporated the photophysical properties of the Tb(III) probe and the
      instrument's light-collection characteristics. Despite low photon counts, images
      of Tb(III)/green fluorescent protein FRET with a signal/noise ratio >= 7 were
      acquired, and a 90% change in the ratiometric FRET signal was measured. This
      study shows that the sensitivity and precision of lanthanide-based cellular
      microscopy can approach that of conventional FRET microscopy with fluorescent
      proteins. The results should encourage further development of lanthanide
      biosensors that can measure analyte concentration, enzyme activation, and protein
      protein interactions in live cells. 

PMID- 26200861
TI  - Palladin mediates stiffness-induced fibroblast activation in the tumor
      microenvironment.
AB  - Mechanical properties of the tumor microenvironment have emerged as key factors
      in tumor progression. It has been proposed that increased tissue stiffness can
      transform stromal fibroblasts into carcinoma-associated fibroblasts. However, it
      is unclear whether the three to five times increase in stiffness seen in tumor
      adjacent stroma is sufficient for fibroblast activation. In this study we
      developed a three-dimensional (3D) hydrogel model with precisely tunable
      stiffness and show that a physiologically relevant increase in stiffness is
      sufficient to lead to fibroblast activation. We found that soluble factors
      including CC-motif chemokine ligand (CCL) chemokines and fibronectin are
      necessary for this activation, and the combination of C-C chemokine receptor type
      4 (CCR4) chemokine receptors and beta1 and beta3 integrins are necessary to
      transduce these chemomechanical signals. We then show that these chemomechanical
      signals lead to the gene expression changes associated with fibroblast activation
      via a network of intracellular signaling pathways that include focal adhesion
      kinase (FAK) and phosphoinositide 3-kinase (PI3K). Finally, we identify the actin
      associated protein palladin as a key node in these signaling pathways that result
      in fibroblast activation. 

PMID- 26200862
TI  - Subconductance gating and voltage sensitivity of sarcoplasmic reticulum K(+)
      channels: a modeling approach.
AB  - Sarcoplasmic reticulum (SR) K(+) channels are voltage-regulated channels that are
      thought to be actively gating when the membrane potential across the SR is close
      to zero as is expected physiologically. A characteristic of SR K(+) channels is
      that they gate to subconductance open states but the relevance of the
      subconductance events and their contribution to the overall current flowing
      through the channels at physiological membrane potentials is not known. We have
      investigated the relationship between subconductance and full conductance
      openings and developed kinetic models to describe the voltage sensitivity of
      channel gating. Because there may be two subtypes of SR K(+) channels (TRIC-A and
      TRIC-B) present in most tissues, to conduct our study on a homogeneous population
      of SR K(+) channels, we incorporated SR vesicles derived from Tric-a knockout
      mice into artificial membranes to examine the remaining SR K(+) channel (TRIC-B)
      function. The channels displayed very low open probability (Po) at negative
      potentials (<=0 mV) and opened predominantly to subconductance open states.
      Positive holding potentials primarily increased the frequency of subconductance
      state openings and thereby increased the number of subsequent transitions into
      the full open state, although a slowing of transitions back to the sublevels was
      also important. We investigated whether the subconductance gating could arise as
      an artifact of incomplete resolution of rapid transitions between full open and
      closed states; however, we were not able to produce a model that could fit the
      data as well as one that included multiple distinct current amplitudes. Our
      results suggest that the apparent subconductance openings will provide most of
      the K(+) flux when the SR membrane potential is close to zero. The relative
      contribution played by openings to the full open state would increase if negative
      charge developed within the SR thus increasing the capacity of the channel to
      compensate for ionic imbalances. 

PMID- 26200863
TI  - MD simulations and FRET reveal an environment-sensitive conformational plasticity
      of importin-beta.
AB  - The nuclear pore complex mediates nucleocytoplasmic transport of macromolecules
      in eukaryotic cells. Transport through the pore is restricted by a hydrophobic
      selectivity filter comprising disordered phenylalanine-glycine-rich repeats of
      nuclear pore proteins. Exchange through the pore requires specialized transport
      receptors, called exportins and importins, that interact with cargo proteins in a
      RanGTP-dependent manner. These receptors are highly flexible superhelical
      structures composed of HEAT-repeat motifs that adopt various degrees of extension
      in crystal structures. Here, we performed molecular-dynamics simulations using
      crystal structures of Importin-beta in its free form or in complex with nuclear
      localization signal peptides as the starting conformation. Our simulations
      predicted that initially compact structures would adopt extended conformations in
      hydrophilic buffers, while contracted conformations would dominate in more
      hydrophobic solutions, mimicking the environment of the nuclear pore. We
      confirmed this experimentally by Forster resonance energy transfer experiments
      using dual-fluorophore-labeled Importin-beta. These observations explain
      seemingly contradictory crystal structures and suggest a possible mechanism for
      cargo protection during passage of the nuclear pore. Such hydrophobic switching
      may be a general principle for environmental control of protein function. 

PMID- 26200864
TI  - Kinetic and vibrational isotope effects of proton transfer reactions in
      channelrhodopsin-2.
AB  - Channelrhodopsins (ChRs) are light-gated cation channels. After blue-light
      excitation, the protein undergoes a photocycle with different intermediates.
      Here, we have recorded transient absorbance changes of ChR2 from Chlamydomonas
      reinhardtii in the visible and infrared regions with nanosecond time resolution,
      the latter being accomplished using tunable quantum cascade lasers. Because
      proton transfer reactions play a key role in channel gating, we determined
      vibrational as well as kinetic isotope effects (VIEs and KIEs) of carboxylic
      groups of various key aspartic and glutamic acid residues by monitoring their C=O
      stretching vibrations in H2O and in D2O. D156 exhibits a substantial KIE (>2) in
      its deprotonation and reprotonation, which substantiates its role as the internal
      proton donor to the retinal Schiff base. The unusual VIE of D156, upshifted from
      1736 cm(-1) to 1738 cm(-1) in D2O, was scrutinized by studying the D156E variant.
      The C=O stretch of E156 shifted down by 8 cm(-1) in D2O, providing evidence for
      the accessibility of the carboxylic group. The C=O stretching band of E90
      exhibits a VIE of 9 cm(-1) and a KIE of ~2 for the de- and the reprotonation
      reactions during the lifetime of the late desensitized state. The KIE of 1
      determined in the time range from 20 ns to 5 ms is incompatible with early
      deprotonation of E90. 

PMID- 26200865
TI  - Regulation of membrane-shape transitions induced by I-BAR domains.
AB  - I-BAR proteins are well-known actin-cytoskeleton adaptors and have been observed
      to be involved in the formation of plasma membrane protrusions (filopodia). I-BAR
      proteins contain an all-helical, crescent-shaped IRSp53-MIM domain (IMD) dimer
      that is believed to be able to couple with a membrane shape. This coupling could
      involve the sensing and even the generation of negative plasma membrane
      curvature. Indeed, the in vitro studies have shown that IMDs can induce inward
      tubulation of liposomes. While N-BAR domains, which generate positive membrane
      curvature, have received a considerable amount of attention from both theory and
      experiments, the mechanisms of curvature coupling through IMDs are comparatively
      less studied and understood. Here we used a membrane-shape stability assay
      developed recently in our lab to quantitatively characterize IMD-induced membrane
      shape transitions. We determined a membrane-shape stability diagram for IMDs that
      reveals how membrane tension and protein density can comodulate the generation of
      IMD-induced membrane protrusions. From comparison to analytical theory, we
      determine three key parameters that characterize the curvature coupling of IMD.
      We find that the curvature generation capacity of IMDs is significantly stronger
      compared to that of endophilin, an N-BAR protein known to be involved in plasma
      membrane shape transitions. Contrary to N-BAR domains, where amphipathic helix
      insertion is known to promote its membrane curvature generation, for IMDs we find
      that amphipathic helices inhibit membrane shape transitions, consistent with the
      inverse curvature that IMDs generate. Importantly, in both of these types of BAR
      domains, electrostatic interactions affect membrane-binding capacity, but do not
      appear to affect the curvature generation capacity of the protein. These two
      types of BAR domain proteins show qualitatively similar membrane shape stability
      diagrams, suggesting an underlying ubiquitous mechanism by which peripheral
      proteins regulate membrane curvature. 

PMID- 26200866
TI  - Small-angle X-ray scattering of the cholesterol incorporation into human ApoA1
      POPC discoidal particles.
AB  - Structural and functional aspects of high-density lipoproteins have been studied
      for over half a century. Due to the plasticity of this highly complex system, new
      aspects continue to be discovered. Here, we present a structural study of the
      human Apolipoprotein A1 (ApoA1) and investigate the role of its N-terminal
      domain, the so-called globular domain of ApoA1, in discoidal complexes with
      phospholipids and increasing amounts of cholesterol. Using a combination of
      solution-based small-angle x-ray scattering (SAXS) and molecular constrained data
      modeling, we show that the ApoA1-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
      (POPC)-based particles are disk shaped with an elliptical cross section and
      composed by a central lipid bilayer surrounded by two stabilizing ApoA1 proteins.
      This structure is very similar to the particles formed in the so-called nanodisc
      system, which is based on N-terminal truncated ApoA1 protein. Although it is
      commonly agreed that the nanodisc is plain disk shaped, several more advanced
      structures have been proposed for the full-length ApoA1 in combination with POPC
      and cholesterol. This prompted us to make a detailed comparative study of the
      ApoA1 and nanodisc systems upon cholesterol uptake. Based on the presented SAXS
      analysis it is found that the N-terminal domains of ApoA1-POPC-cholesterol
      particles are not globular but instead an integrated part of the protein belt
      stabilizing the particles. Upon incorporation of increasing amounts of
      cholesterol, the presence of the N-terminal domain allows the bilayer thickness
      to increase while maintaining an overall flat bilayer structure. This is
      contrasted by the energetically more strained and less favorable lens shape
      required to fit the SAXS data from the N-terminal truncated nanodisc system upon
      cholesterol incorporation. This suggests that the N-terminal domain of ApoA1
      actively participates in the stabilization of the ApoA1-POPC-cholesterol
      discoidal particle and allows for a more optimal lipid packing upon cholesterol
      uptake. 

PMID- 26200867
TI  - High cholesterol obviates a prolonged hemifusion intermediate in fast SNARE
      mediated membrane fusion.
AB  - Cholesterol is essential for exocytosis in secretory cells, but the exact
      molecular mechanism by which it facilitates exocytosis is largely unknown.
      Distinguishing contributions from the lateral organization and dynamics of
      membrane proteins to vesicle docking and fusion and the promotion of fusion pores
      by negative intrinsic spontaneous curvature and other mechanical effects of
      cholesterol have been elusive. To shed more light on this process, we examined
      the effect of cholesterol on SNARE-mediated membrane fusion in a single-vesicle
      assay that is capable of resolving docking and elementary steps of fusion with
      millisecond time resolution. The effect of cholesterol on fusion pore formation
      between synaptobrevin-2 (VAMP-2)-containing proteoliposomes and acceptor t-SNARE
      complex-containing planar supported bilayers was examined using both membrane and
      content fluorescent markers. This approach revealed that increasing cholesterol
      in either the t-SNARE or the v-SNARE membrane favors a mechanism of direct fusion
      pore opening, whereas low cholesterol favors a mechanism leading to a long-lived
      (>5 s) hemifusion state. The amount of cholesterol in the target membrane had no
      significant effect on docking of synaptobrevin vesicles. Comparative studies with
      alpha-tocopherol (vitamin E) show that the negative intrinsic spontaneous
      curvature of cholesterol and its presumed promotion of a very short-lived (<50
      ms) lipid stalk intermediate is the main factor that favors rapid fusion pore
      opening at high cholesterol. This study also shows that this single-vesicle
      fusion assay can distinguish between hemifusion and full fusion with only a
      single lipid dye, thereby freeing up a fluorescence channel for the simultaneous
      measurement of another parameter in fast time-resolved fusion assays. 

PMID- 26200868
TI  - DMSO induces dehydration near lipid membrane surfaces.
AB  - Dimethyl sulfoxide (DMSO) has been broadly used in biology as a cosolvent, a
      cryoprotectant, and an enhancer of membrane permeability, leading to the general
      assumption that DMSO-induced structural changes in cell membranes and their
      hydration water play important functional roles. Although the effects of DMSO on
      the membrane structure and the headgroup dehydration have been extensively
      studied, the mechanism by which DMSO invokes its effect on lipid membranes and
      the direct role of water in this process are unresolved. By directly probing the
      translational water diffusivity near unconfined lipid vesicle surfaces, the lipid
      headgroup mobility, and the repeat distances in multilamellar vesicles, we found
      that DMSO exclusively weakens the surface water network near the lipid membrane
      at a bulk DMSO mole fraction (XDMSO) of <0.1, regardless of the lipid composition
      and the lipid phase. Specifically, DMSO was found to effectively destabilize the
      hydration water structure at the lipid membrane surface at XDMSO <0.1, lower the
      energetic barrier to dehydrate this surface water, whose displacement otherwise
      requires a higher activation energy, consequently yielding compressed
      interbilayer distances in multilamellar vesicles at equilibrium with unaltered
      bilayer thicknesses. At XDMSO >0.1, DMSO enters the lipid interface and restricts
      the lipid headgroup motion. We postulate that DMSO acts as an efficient
      cryoprotectant even at low concentrations by exclusively disrupting the water
      network near the lipid membrane surface, weakening the cohesion between water and
      adhesion of water to the lipid headgroups, and so mitigating the stress induced
      by the volume change of water during freeze-thaw. 

PMID- 26200869
TI  - Titin domains progressively unfolded by force are homogenously distributed along
      the molecule.
AB  - Titin is a giant filamentous protein of the muscle sarcomere in which stretch
      induces the unfolding of its globular domains. However, the mechanisms of how
      domains are progressively selected for unfolding and which domains eventually
      unfold have for long been elusive. Based on force-clamp optical tweezers
      experiments we report here that, in a paradoxical violation of mechanically
      driven activation kinetics, neither the global domain unfolding rate, nor the
      folded-state lifetime distributions of full-length titin are sensitive to force.
      This paradox is reconciled by a gradient of mechanical stability so that domains
      are gradually selected for unfolding as the magnitude of the force field
      increases. Atomic force microscopic screening of extended titin molecules
      revealed that the unfolded domains are distributed homogenously along the entire
      length of titin, and this homogeneity is maintained with increasing overstretch.
      Although the unfolding of domains with progressively increasing mechanical
      stability makes titin a variable viscosity damper, the spatially randomized
      variation of domain stability ensures that the induced structural changes are not
      localized but are distributed along the molecule's length. Titin may thereby
      provide complex safety mechanims for protecting the sarcomere against structural
      disintegration under excessive mechanical conditions. 

PMID- 26200870
TI  - An information-based approach to change-point analysis with applications to
      biophysics and cell biology.
AB  - This article describes the application of a change-point algorithm to the
      analysis of stochastic signals in biological systems whose underlying state
      dynamics consist of transitions between discrete states. Applications of this
      analysis include molecular-motor stepping, fluorophore bleaching,
      electrophysiology, particle and cell tracking, detection of copy number variation
      by sequencing, tethered-particle motion, etc. We present a unified approach to
      the analysis of processes whose noise can be modeled by Gaussian, Wiener, or
      Ornstein-Uhlenbeck processes. To fit the model, we exploit explicit, closed-form
      algebraic expressions for maximum-likelihood estimators of model parameters and
      estimated information loss of the generalized noise model, which can be computed
      extremely efficiently. We implement change-point detection using the frequentist
      information criterion (which, to our knowledge, is a new information criterion).
      The frequentist information criterion specifies a single, information-based
      statistical test that is free from ad hoc parameters and requires no prior
      probability distribution. We demonstrate this information-based approach in the
      analysis of simulated and experimental tethered-particle-motion data. 

PMID- 26200871
TI  - Directional bleb formation in spherical cells under temperature gradient.
AB  - Living cells sense absolute temperature and temporal changes in temperature using
      biological thermosensors such as ion channels. Here, we reveal, to our knowledge,
      a novel mechanism of sensing spatial temperature gradients within single cells.
      Spherical mitotic cells form directional membrane extensions (polar blebs) under
      sharp temperature gradients (>=~0.065 degrees C MUm(-1); 1.3 degrees C
      temperature difference within a cell), which are created by local heating with a
      focused 1455-nm laser beam under an optical microscope. On the other hand,
      multiple nondirectional blebs are formed under gradual temperature gradients or
      uniform heating. During heating, the distribution of actomyosin complexes becomes
      inhomogeneous due to a break in the symmetry of its contractile force,
      highlighting the role of the actomyosin complex as a sensor of local temperature
      gradients. 

PMID- 26200872
TI  - Ligand-induced changes of the apparent transition-state position in mechanical
      protein unfolding.
AB  - Force-spectroscopic measurements of ligand-receptor systems and the
      unfolding/folding of nucleic acids or proteins reveal information on the
      underlying energy landscape along the pulling coordinate. The slope Deltax(?) of
      the force-dependent unfolding/unbinding rates is interpreted as the distance from
      the folded/bound state to the transition state for unfolding/unbinding and,
      hence, often related to the mechanical compliance of the sample molecule. Here we
      show that in ligand-binding proteins, the experimentally inferred Deltax(?) can
      depend on the ligand concentration, unrelated to changes in mechanical
      compliance. We describe the effect in single-molecule, force-spectroscopy
      experiments of the calcium-binding protein calmodulin and explain it in a simple
      model where mechanical unfolding and ligand binding occur on orthogonal reaction
      coordinates. This model predicts changes in the experimentally inferred
      Deltax(?), depending on ligand concentration and the associated shift of the
      dominant barrier between the two reaction coordinates. We demonstrate
      quantitative agreement between experiments and simulations using a realistic six
      state kinetic scheme using literature values for calcium-binding kinetics and
      affinities. Our results have important consequences for the interpretation of
      force-spectroscopic data of ligand-binding proteins. 

PMID- 26200873
TI  - Stabilizing the central part of tropomyosin increases the bending stiffness of
      the thin filament.
AB  - A two-beam optical trap was used to measure the bending stiffness of F-actin and
      reconstructed thin filaments. A dumbbell was formed by a filament segment
      attached to two beads that were held in the two optical traps. One trap was
      static and held a bead used as a force transducer, whereas an acoustooptical
      deflector moved the beam holding the second bead, causing stretch of the
      dumbbell. The distance between the beads was measured using image analysis of
      micrographs. An exact solution to the problem of bending of an elastic filament
      attached to two beads and subjected to a stretch was used for data analysis.
      Substitution of noncanonical residues in the central part of tropomyosin with
      canonical ones, G126R and D137L, and especially their combination, caused an
      increase in the bending stiffness of the thin filaments. The data confirm that
      the effect of these mutations on the regulation of actin-myosin interactions may
      be caused by an increase in tropomyosin stiffness. 

PMID- 26200875
TI  - Calcium ions modulate the mechanics of tomato bushy stunt virus.
AB  - Viral particles are endowed with physicochemical properties whose modulation
      confers certain metastability to their structures to fulfill each task of the
      viral cycle. Here, we investigate the effects of swelling and ion depletion on
      the mechanical stability of individual tomato bushy stunt virus nanoparticles
      (TBSV-NPs). Our experiments show that calcium ions modulate the mechanics of the
      capsid: the sequestration of calcium ions from the intracapsid binding sites
      reduces rigidity and resilience in ~24% and 40%, respectively. Interestingly,
      mechanical deformations performed on native TBSV-NPs induce an analogous result.
      In addition, TBSV-NPs do not show capsomeric vacancies after surpassing the
      elastic limit. We hypothesize that even though there are breakages among
      neighboring capsomers, RNA-capsid protein interaction prevents the release of
      capsid subunits. This work shows the mechanical role of calcium ions in viral
      shell stability and identifies TBSV-NPs as malleable platforms based on protein
      cages for cargo transportation at the nanoscale. 

PMID- 26200874
TI  - Green fluorescent protein with anionic tryptophan-based chromophore and long
      fluorescence lifetime.
AB  - Spectral diversity of fluorescent proteins, crucial for multiparameter imaging,
      is based mainly on chemical diversity of their chromophores. Recently we have
      reported, to our knowledge, a new green fluorescent protein WasCFP-the first
      fluorescent protein with a tryptophan-based chromophore in the anionic state.
      However, only a small portion of WasCFP molecules exists in the anionic state at
      physiological conditions. In this study we report on an improved variant of
      WasCFP, named NowGFP, with the anionic form dominating at 37 degrees C and
      neutral pH. It is 30% brighter than enhanced green fluorescent protein (EGFP) and
      exhibits a fluorescence lifetime of 5.1 ns. We demonstrated that signals of
      NowGFP and EGFP can be clearly distinguished by fluorescence lifetime in various
      models, including mammalian cells, mouse tumor xenograft, and Drosophila larvae.
      NowGFP thus provides an additional channel for multiparameter fluorescence
      lifetime imaging microscopy of green fluorescent proteins. 

PMID- 26200876
TI  - Structural origins of misfolding propensity in the platelet adhesive von
      Willebrand factor A1 domain.
AB  - The von Willebrand factor (VWF) A1 and A3 domains are structurally isomorphic yet
      exhibit distinct mechanisms of unfolding. The A1 domain, responsible for platelet
      adhesion to VWF in hemostasis, unfolds through a molten globule intermediate in
      an apparent three-state mechanism, while A3 unfolds by a classical two-state
      mechanism. Inspection of the sequences or structures alone does not elucidate the
      source of this thermodynamic conundrum; however, the three-state character of the
      A1 domain suggests that it has more than one cooperative substructure yielding
      two separate unfolding transitions not present in A3. We investigate the extent
      to which structural elements contributing to intermediate conformations can be
      identified using a residue-specific implementation of the structure-energy
      equivalence-of-domains algorithm (SEED), which parses proteins of known structure
      into their constituent thermodynamically cooperative components using protein
      group-specific, transfer free energies. The structural elements computed to
      contribute to the non-two-state character coincide with regions where Von
      Willebrand disease mutations induce misfolded molten globule conformations of the
      A1 domain. This suggests a mechanism for the regulation of rheological platelet
      adhesion to A1 based on cooperative flexibility of the alpha2 and alpha3 helices
      flanking the platelet GPIbalpha receptor binding interface. 

PMID- 26200877
TI  - A force balance can explain local and global cell movements during early
      zebrafish development.
AB  - Embryonic morphogenesis takes place via a series of dramatic collective cell
      movements. The mechanisms that coordinate these intricate structural
      transformations across an entire organism are not well understood. In this study,
      we used gentle mechanical deformation of developing zebrafish embryos to probe
      the role of physical forces in generating long-range intercellular coordination
      during epiboly, the process in which the blastoderm spreads over the yolk cell.
      Geometric distortion of the embryo resulted in nonuniform blastoderm migration
      and realignment of the anterior-posterior (AP) axis, as defined by the locations
      at which the head and tail form, toward the new long axis of the embryo and away
      from the initial animal-vegetal axis defined by the starting location of the
      blastoderm. We found that local alterations in the rate of blastoderm migration
      correlated with the local geometry of the embryo. Chemical disruption of the
      contractile ring of actin and myosin immediately vegetal to the blastoderm margin
      via Ca(2+) reduction or treatment with blebbistatin restored uniform migration
      and eliminated AP axis reorientation in mechanically deformed embryos; it also
      resulted in cellular disorganization at the blastoderm margin. Our results
      support a model in which tension generated by the contractile actomyosin ring
      coordinates epiboly on both the organismal and cellular scales. Our observations
      likewise suggest that the AP axis is distinct from the initial animal-vegetal
      axis in zebrafish. 

PMID- 26200878
TI  - A human ventricular myocyte model with a refined representation of excitation
      contraction coupling.
AB  - Cardiac Ca(2+)-induced Ca(2+) release (CICR) occurs by a regenerative activation
      of ryanodine receptors (RyRs) within each Ca(2+)-releasing unit, triggered by the
      activation of L-type Ca(2+) channels (LCCs). CICR is then terminated, most
      probably by depletion of Ca(2+) in the junctional sarcoplasmic reticulum (SR).
      Hinch et al. previously developed a tightly coupled LCC-RyR mathematical model,
      known as the Hinch model, that enables simulations to deal with a variety of
      functional states of whole-cell populations of a Ca(2+)-releasing unit using a
      personal computer. In this study, we developed a membrane excitation-contraction
      model of the human ventricular myocyte, which we call the human ventricular cell
      (HuVEC) model. This model is a hybrid of the most recent HuVEC models and the
      Hinch model. We modified the Hinch model to reproduce the regenerative activation
      and termination of CICR. In particular, we removed the inactivated RyR state and
      separated the single step of RyR activation by LCCs into triggering and
      regenerative steps. More importantly, we included the experimental measurement of
      a transient rise in Ca(2+) concentrations ([Ca(2+)], 10-15 MUM) during CICR in
      the vicinity of Ca(2+)-releasing sites, and thereby calculated the effects of the
      local Ca(2+) gradient on CICR as well as membrane excitation. This HuVEC model
      successfully reconstructed both membrane excitation and key properties of CICR.
      The time course of CICR evoked by an action potential was accounted for by
      autonomous changes in an instantaneous equilibrium open probability of couplons.
      This autonomous time course was driven by a core feedback loop including the
      pivotal local [Ca(2+)], influenced by a time-dependent decay in the SR Ca(2+)
      content during CICR. 

PMID- 26200879
TI  - Emergent stem cell homeostasis in the C. elegans germline is revealed by hybrid
      modeling.
AB  - The establishment of homeostasis among cell growth, differentiation, and
      apoptosis is of key importance for organogenesis. Stem cells respond to
      temporally and spatially regulated signals by switching from mitotic
      proliferation to asymmetric cell division and differentiation. Executable
      computer models of signaling pathways can accurately reproduce a wide range of
      biological phenomena by reducing detailed chemical kinetics to a discrete, finite
      form. Moreover, coordinated cell movements and physical cell-cell interactions
      are required for the formation of three-dimensional structures that are the
      building blocks of organs. To capture all these aspects, we have developed a
      hybrid executable/physical model describing stem cell proliferation,
      differentiation, and homeostasis in the Caenorhabditis elegans germline. Using
      this hybrid model, we are able to track cell lineages and dynamic cell movements
      during germ cell differentiation. We further show how apoptosis regulates germ
      cell homeostasis in the gonad, and propose a role for intercellular pressure in
      developmental control. Finally, we use the model to demonstrate how an executable
      model can be developed from the hybrid system, identifying a mechanism that
      ensures invariance in fate patterns in the presence of instability. 

PMID- 26200881
TI  - Threshold of microvascular occlusion: injury size defines the thrombosis
      scenario.
AB  - Damage to the blood vessel triggers formation of a hemostatic plug, which is
      meant to prevent bleeding, yet the same phenomenon may result in a total blockade
      of a blood vessel by a thrombus, causing severe medical conditions. Here, we show
      that the physical interplay between platelet adhesion and hemodynamics in a
      microchannel manifests in a critical threshold behavior of a growing thrombus.
      Depending on the size of injury, two distinct dynamic pathways of thrombosis were
      found: the formation of a nonocclusive plug, if injury length does not exceed the
      critical value, and the total occlusion of the vessel by the thrombus otherwise.
      We develop a mathematical model that demonstrates that switching between these
      regimes occurs as a result of a saddle-node bifurcation. Our study reveals the
      mechanism of self-regulation of thrombosis in blood microvessels and explains
      experimentally observed distinctions between thrombi of different physical
      etiology. This also can be useful for the design of platelet-aggregation-inspired
      engineering solutions. 

PMID- 26200880
TI  - Modeling of glucose-induced cAMP oscillations in pancreatic beta cells: cAMP
      rocks when metabolism rolls.
AB  - Recent advances in imaging technology have revealed oscillations of cyclic
      adenosine monophosphate (cAMP) in insulin-secreting cells. These oscillations may
      be in phase with cytosolic calcium oscillations or out of phase. cAMP
      oscillations have previously been modeled as driven by oscillations in calcium,
      based on the known dependence of the enzymes that generate cAMP (adenylyl
      cyclase) and degrade it (phosphodiesterase). However, cAMP oscillations have also
      been reported to occur in the absence of calcium oscillations. Motivated by
      similarities between the properties of cAMP and metabolic oscillations in
      pancreatic beta cells, we propose here that in addition to direct control by
      calcium, cAMP is controlled by metabolism. Specifically, we hypothesize that AMP
      inhibits adenylyl cyclase. We incorporate this hypothesis into the dual
      oscillator model for beta cells, in which metabolic (glycolytic) oscillations
      cooperate with modulation of ion channels and metabolism by calcium. We show that
      the combination of oscillations in AMP and calcium in the dual oscillator model
      can account for the diverse oscillatory patterns that have been observed, as well
      as for experimental perturbations of those patterns. Predictions to further test
      the model are provided. 

PMID- 26200882
TI  - Differences Between Bilateral Adrenal Incidentalomas and Unilateral Lesions.
AB  - IMPORTANCE: Adrenal incidentalomas are found in 1% to 5% of abdominal cross
      sectional imaging studies. Although the workup and management of unilateral
      lesions are well established, limited information exists for bilateral
      incidentalomas. OBJECTIVE: To compare the natural history of patients having
      bilateral incidentalomas with those having unilateral incidentalomas. DESIGN,
      SETTING, AND PARTICIPANTS: Retrospective analysis of a prospective database of
      consecutive patients referred to an academic multidisciplinary adrenal
      conference. The setting was a tertiary care university hospital among a cohort of
      500 patients with adrenal lesions between July 1, 2009, and July 1, 2014. MAIN
      OUTCOMES AND MEASURES: Prevalence, age, imaging characteristics, biochemical
      workup, any intervention, and final diagnosis. RESULTS: Twenty-three patients
      with bilateral incidentalomas and 112 patients with unilateral incidentalomas
      were identified. The mean age at diagnosis of bilateral lesions was 58.7 years.
      The mean lesion size was 2.4 cm on the right side and 2.8 cm on the left side.
      Bilateral incidentalomas were associated with a significantly higher prevalence
      of subclinical Cushing syndrome (21.7% [5 of 23] vs 6.2% [7 of 112]) (P = .009)
      and a significantly lower prevalence of pheochromocytoma (4.3% [1 of 23] vs 19.6%
      [22 of 112]) (P = .003) compared with unilateral lesions, while rates of
      hyperaldosteronism were similar in both groups (4.3% [1 of 23] vs 5.4% [6 of
      112]) (P > .99). Only one patient with bilateral incidentalomas underwent
      unilateral resection. The mean follow-up was 4 years (range, 1.2-13.0 years).
      There were no occult adrenocortical carcinomas. CONCLUSIONS AND RELEVANCE:
      Bilateral incidentalomas are more likely to be associated with subclinical
      Cushing syndrome and less likely to be pheochromocytomas. Although patients with
      bilateral incidentalomas undergo a workup similar to that in patients with
      unilateral lesions, differences in their natural history warrant a greater index
      of suspicion for subclinical Cushing syndrome.

PMID- 26200883
TI  - HIV-1 Genetic Diversity and Transmitted Drug Resistance Among Recently Infected
      Individuals at Men Who Have Sex with Men Sentinel Surveillance Points in Hebei
      Province, China.
AB  - For this study, 50 HIV-1 plasma samples of recently infected men who have sex
      with men (MSM) were amplified and sequenced. Multiple subtypes were identified by
      phylogenetic analyses of HIV-1 gag, env, and pol gene regions, including CRF01_AE
      (56.0%), CRF07_BC (30.0%), subtype B (12.0%), and unique recombinant forms (URFs,
      6.0%). CRF01_AE was the most frequent genotype in the epidemic. Three
      recombination patterns of URFs were identified: 01BC, 01B, and 01C. The rate of
      HIV-1 transmitted drug resistance (TDR) mutation (M46L) was 2.08% (1/48). URFs
      and TDR first identified in this study suggest that HIV-1 prevalence is more and
      more complicated, and HIV-1 drug-resistant strains have begun to spread among at
      risk populations in Hebei. Our findings can provide vital information for an
      efficient surveillance system and strategic HIV prevention and control measures
      in China by revealing the evolutionary status and HIV-1 TDR of HIV-1 strains
      among recently infected MSM in Hebei Province. 

PMID- 26200884
TI  - Blood pressure control and risk profile in poststroke survivors: a comparison
      with the general population.
AB  - OBJECTIVE: Recurrent strokes are associated with higher mortality, greater
      disability, and increased healthcare costs compared with first-ever stroke.
      Lifestyle measures and drug treatment in secondary prevention decrease the risk
      of recurrence while improving the quality of life of patients. The objective of
      this study was to determine the prevalence of hypertension and other
      cardiovascular risk factors in stroke survivors and population controls. METHODS
      AND RESULTS: A total of 424 poststroke survivors (aged 66.0 +/- 10.4 years) were
      examined 6-36 months after their first ischemic stroke. Controls of similar age
      and from the same geographic region were selected from the database of the Czech
      post-Multinational MONItoring of trends and determinants in CArdiovascular
      disease Study. Hypertension was found to be the most prevalent risk factor
      affecting 91.5% of stroke survivors and 71.8% of controls. Use of
      antihypertensive drugs was reported in 79.5% of stroke survivors and 56.7% of
      controls. However, blood pressure lower than 140/90 mmHg was achieved in only
      49.5% of hypertensive stroke survivors. More than 60% of stroke survivors used
      statins but low-density lipoprotein-cholesterol lower than 2.5 mmol/l was
      achieved in only 47.4 and 37% of male and female poststroke survivors,
      respectively. About a third of poststroke patients continue to smoke, and obesity
      is a major problem, particularly in women (prevalence 47%), who also have a high
      prevalence of diabetes. CONCLUSION: We found a high prevalence and poor control
      of major cardiovascular risk factors in patients surviving their first-ever
      ischemic stroke, thus showing poor implementation of guidelines for secondary
      prevention in clinical practice.

PMID- 26200885
TI  - The Applicability of the Distribution Coefficient, KD, Based on Non-Aggregated
      Particulate Samples from Lakes with Low Suspended Solids Concentrations.
AB  - Separate phases of metal partitioning behaviour in freshwater lakes that receive
      varying degrees of atmospheric contamination and have low concentrations of
      suspended solids were investigated to determine the applicability of the
      distribution coefficient, KD. Concentrations of Pb, Ni, Co, Cu, Cd, Cr, Hg and Mn
      were determined using a combination of filtration methods, bulk sample collection
      and digestion and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).
      Phytoplankton biomass, suspended solids concentrations and the organic content of
      the sediment were also analysed. By distinguishing between the phytoplankton and
      (inorganic) lake sediment, transient variations in KD were observed. Suspended
      solids concentrations over the 6-month sampling campaign showed no correlation
      with the KD (n = 15 for each metal, p > 0.05) for Mn (r2 = 0.0063), Cu (r2 =
      0.0002, Cr (r2 = 0.021), Ni (r2 = 0.0023), Cd (r2 = 0.00001), Co (r2 = 0.096), Hg
      (r2 = 0.116) or Pb (r2 = 0.164). The results implied that colloidal matter had
      less opportunity to increase the dissolved (filter passing) fraction, which
      inhibited the spurious lowering of KD. The findings conform to the increasingly
      documented theory that the use of KD in modelling may mask true information on
      metal partitioning behaviour. The root mean square error of prediction between
      the directly measured total metal concentrations and those modelled based on the
      separate phase fractions were +/- 3.40, 0.06, 0.02, 0.03, 0.44, 484.31, 80.97 and
      0.1 MUg/L for Pb, Cd, Mn, Cu, Hg, Ni, Cr and Co respectively. The magnitude of
      error suggests that the separate phase models for Mn and Cu can be used in
      distribution or partitioning models for these metals in lake water. 

PMID- 26200886
TI  - Fast adaptive estimation of multidimensional psychometric functions.
AB  - Recently in vision science there has been great interest in understanding the
      perceptual representations of complex multidimensional stimuli. Therefore, it is
      becoming very important to develop methods for performing psychophysical
      experiments with multidimensional stimuli and efficiently estimating psychometric
      models that have multiple free parameters. In this methodological study, I
      analyze three efficient implementations of the popular Psi method for adaptive
      data collection, two of which are novel approaches to psychophysical experiments.
      Although the standard implementation of the Psi procedure is intractable in
      higher dimensions, I demonstrate that my implementations generalize well to
      complex psychometric models defined in multidimensional stimulus spaces and can
      be implemented very efficiently on standard laboratory computers. I show that my
      implementations may be of particular use for experiments studying how subjects
      combine multiple cues to estimate sensory quantities. I discuss strategies for
      speeding up experiments and suggest directions for future research in this
      rapidly growing area at the intersection of cognitive science, neuroscience, and
      machine learning. 

PMID- 26200887
TI  - Perceptual scales for chromatic and luminance blur in noise textures.
AB  - We have measured the relative perceptual scales for chromatic and luminance blur
      in dense textures comprised of color and luminance Gabors, using a modification
      of the method of paired comparisons. We find that the rate at which perceived
      blur grows with physical blur, when normalized to 1.0 for luminance, is 0.2 for
      red-green and 0.06 for blue-yellow blur. It is argued that the relatively
      severely compressed perceptual scales for red-green and blue-yellow blur are a
      contributary factor to the observation that when the color but not luminance
      layer of an image of a natural scene is blurred, there is little or no impression
      of blur (Wandell, 1995). 

PMID- 26200888
TI  - Beyond the classical receptive field: The effect of contextual stimuli.
AB  - Following the pioneering studies of the receptive field (RF), the RF concept
      gained further significance for visual perception by the discovery of input
      effects from beyond the classical RF. These studies demonstrated that neuronal
      responses could be modulated by stimuli outside their RFs, consistent with the
      perception of induced brightness, color, orientation, and motion. Lesion
      scotomata are similarly modulated perceptually from the surround by RFs that have
      migrated from the interior to the outer edge of the scotoma and in this way
      provide filling-in of the void. Large RFs are advantageous to this task. In
      higher visual areas, such as the middle temporal and inferotemporal lobe, RFs
      increase in size and lose most of their retinotopic organization while encoding
      increasingly complex features. Whereas lower-level RFs mediate perceptual filling
      in, contour integration, and figure-ground segregation, RFs at higher levels
      serve the perception of grouping by common fate, biological motion, and other
      biologically relevant stimuli, such as faces. Studies in alert monkeys while
      freely viewing natural scenes showed that classical and nonclassical RFs
      cooperate in forming representations of the visual world. Today, our
      understanding of the mechanisms underlying the RF is undergoing a quantum leap.
      What had started out as a hierarchical feed-forward concept for simple stimuli,
      such as spots, lines, and bars, now refers to mechanisms involving ascending,
      descending, and lateral signal flow. By extension of the bottom-up paradigm, RFs
      are nowadays understood as adaptive processors, enabling the predictive coding of
      complex scenes. Top-down effects guiding attention and tuned to task-relevant
      information complement the bottom-up analysis. 

PMID- 26200889
TI  - Eyes on emergence: Fast detection yet slow recognition of emerging images.
AB  - Visual object recognition occurs at the intersection of visual perception and
      visual cognition. It typically occurs very fast and it has therefore been
      difficult to disentangle its constituent processes. Recognition time can be
      extended when using images with emergent properties, suggesting they may help
      examining how visual recognition unfolds over time. Until now, their use has been
      constrained by limited availability. We used a set of stimuli with emergent
      properties-akin to the famous Gestalt image of a Dalmatian-in combination with
      eye tracking to examine the processes underlying object recognition. To test
      whether cognitive processes influenced eye movement behavior during recognition,
      an unprimed and three primed groups were included. Recognition times were
      relatively long (median ~ 5s for the unprimed group), confirming the object's
      emergent properties. Surprisingly, within the first 500 ms, the majority of
      fixations were already aimed at the object. Computational models of saliency
      could not explain these initial fixations. This suggests that observers relied on
      image statistics not captured by saliency models. For the primed groups,
      recognition times were reduced. However, threshold-free cluster enhancement-based
      analysis of the time courses indicated that viewing behavior did not differ
      between the groups, neither during the initial viewing nor around the moment of
      recognition. This implies that eye movements are mainly driven by perceptual
      processes and not affected by cognition. It further suggests that priming mainly
      boosts the observer's confidence in the decision reached. We conclude that
      emerging images can be a useful tool to dissociate the perceptual and cognitive
      contributions to visual object recognition. 

PMID- 26200890
TI  - Allocation of attention during pursuit of large objects is no different than
      during fixation.
AB  - Attention allocation during pursuit of a spot is usually characterized as
      asymmetric with more attention placed ahead of the target than behind it.
      However, attention is symmetrically allocated across larger pursuit stimuli. An
      unresolved issue is how tightly attention is constrained on large stimuli during
      pursuit. Although some work shows it is tightly locked to the fovea, other work
      shows it is allocated flexibly. To investigate this, we had observers perform a
      character identification task on large pursuit stimuli composed of arrays of
      five, nine, or 15 characters spaced between 0.6 degrees  and 4.0 degrees  apart.
      Initially, the characters were identical, but at a random time, they all changed
      briefly, rendering one of them unique. Observers identified the unique character.
      Consistent with previous literature, attention appeared narrow and symmetric
      around the pursuit target for tightly spaced (0.6 degrees ) characters.
      Increasing spacing dramatically expanded the attention scope, presumably by
      mitigating crowding. However, when we controlled for crowding, performance was
      limited by set size, suffering more for eccentric targets. Interestingly, the
      same limitations on attention allocation were observed with stationary and
      pursued stimuli-evidence that attention operates similarly during fixation and
      pursuit of a stimulus that extends into the periphery. The results suggest that
      attention is flexibly allocated during pursuit, but performance is limited by
      crowding and set size. In addition, performing the identification task did not
      hurt pursuit performance, further evidence that pursuit of large stimuli is
      relatively inattentive. 

PMID- 26200891
TI  - Expectations developed over multiple timescales facilitate visual search
      performance.
AB  - Our perception of the world is strongly influenced by our expectations, and a
      question of key importance is how the visual system develops and updates its
      expectations through interaction with the environment. We used a visual search
      task to investigate how expectations of different timescales (from the last few
      trials to hours to long-term statistics of natural scenes) interact to alter
      perception. We presented human observers with low-contrast white dots at 12
      possible locations equally spaced on a circle, and we asked them to
      simultaneously identify the presence and location of the dots while manipulating
      their expectations by presenting stimuli at some locations more frequently than
      others. Our findings suggest that there are strong acuity differences between
      absolute target locations (e.g., horizontal vs. vertical) and preexisting long
      term biases influencing observers' detection and localization performance,
      respectively. On top of these, subjects quickly learned about the stimulus
      distribution, which improved their detection performance but caused increased
      false alarms at the most frequently presented stimulus locations. Recent exposure
      to a stimulus resulted in significantly improved detection performance and
      significantly more false alarms but only at locations at which it was more
      probable that a stimulus would be presented. Our results can be modeled and
      understood within a Bayesian framework in terms of a near-optimal integration of
      sensory evidence with rapidly learned statistical priors, which are skewed toward
      the very recent history of trials and may help understanding the time scale of
      developing expectations at the neural level. 

PMID- 26200893
TI  - Aerial Oxidation of a V(IV)-Iminopyridine Hydroquinonate Complex: A Trap for the
      V(IV)-Semiquinonate Radical Intermediate.
AB  - The reaction of 2,5-bis[N,N'-bis(2-pyridyl-aminomethyl)aminomethyl]-p
      hydroquinone (H2bpymah) with VO(2+) salts in acetonitrile or water at a low pH
      (2.2-3.5) results in the isolation of [{V(IV)(O)(Cl)}2(MU-bpymah)], the p
      semiquinonate complex [{V(IV)(O)(Cl)}2(MU-bpymas)](OH), the cyclic mixed-valent
      hexanuclear compound [{V(V)(O)(MU-O)V(IV)(O)}(MU-bpymah)]3, and [(V(V)O2)2(MU
      bpymah)]. [{V(IV)(O)(Cl)}2(MU-bpymas)](OH) is an intermediate of the radical
      mediated oxidation of [{V(IV)(O)(Cl)}2(MU-bpymah)] from O2. At lower pH values
      (2.2), a reversible intramolecular electron transfer from the metal to the ligand
      of [{V(IV)(O)(Cl)}2(MU-bpymas)](OH) is induced with the concurrent substitution
      of chlorine atoms by the oxygen-bridging atoms, resulting in the formation of
      [{V(V)(O)(MU-O)V(IV)(O)}(MU-bpymah)]3. The metal complexes were fully
      characterized by X-ray crystallography, infrared (IR) spectroscopy, and magnetic
      measurements in the solid state, as well as by conductivity measurements, UV-vis
      spectroscopy, and electrochemical measurements in solution. The oxidation states
      of the metal ions and ligands were determined by the crystallographic data. The
      [{V(IV)(O)(Cl)}2(MU-bpymah)]-[{V(IV)(O)(Cl)}2(MU-bpymas)](OH) redox process is
      electrochemically reversible. The V(IV) ion in the semiquinonate compound
      exhibits a surprisingly low oxophilicity, resulting in the stabilization of OH(-)
      counterions at acidic pH values. An investigation of the mechanism of this
      reaction reveals that these complexes induce the reduction of O2 to H2O2,
      mimicking the activity of enzymes incorporating two redox-active centers (metal
      organic) in the active site. 

PMID- 26200892
TI  - Atypical processing of voice sounds in infants at risk for autism spectrum
      disorder.
AB  - Adults diagnosed with autism spectrum disorder (ASD) show a reduced sensitivity
      (degree of selective response) to social stimuli such as human voices. In order
      to determine whether this reduced sensitivity is a consequence of years of poor
      social interaction and communication or is present prior to significant
      experience, we used functional MRI to examine cortical sensitivity to auditory
      stimuli in infants at high familial risk for later emerging ASD (HR group, N =
      15), and compared this to infants with no family history of ASD (LR group, N =
      18). The infants (aged between 4 and 7 months) were presented with voice and
      environmental sounds while asleep in the scanner and their behaviour was also
      examined in the context of observed parent-infant interaction. Whereas LR infants
      showed early specialisation for human voice processing in right temporal and
      medial frontal regions, the HR infants did not. Similarly, LR infants showed
      stronger sensitivity than HR infants to sad vocalisations in the right fusiform
      gyrus and left hippocampus. Also, in the HR group only, there was an association
      between each infant's degree of engagement during social interaction and the
      degree of voice sensitivity in key cortical regions. These results suggest that
      at least some infants at high-risk for ASD have atypical neural responses to
      human voice with and without emotional valence. Further exploration of the
      relationship between behaviour during social interaction and voice processing may
      help better understand the mechanisms that lead to different outcomes in at risk
      populations. 

PMID- 26200894
TI  - Use of Medications with Anticholinergic Activity and Self-Reported Injurious
      Falls in Older Community-Dwelling Adults.
AB  - OBJECTIVES: To assess the association between the use of medications with
      anticholinergic activity and the subsequent risk of injurious falls in older
      adults. DESIGN: Prospective, population-based study using data from The Irish
      Longitudinal Study on Ageing. SETTING: Irish population. PARTICIPANTS: Community
      dwelling men and women without dementia aged 65 and older (N = 2,696).
      MEASUREMENTS: Self-reported injurious falls reported once approximately 2 years
      after baseline interview. Self-reported regular medication use at baseline
      interview. Pharmacy dispensing records from the Irish Health Service Executive
      Primary Care Reimbursement Service in a subset (n = 1,553). RESULTS: Nine percent
      of men and 17% of women reported injurious falls. In men, the use of medications
      with definite anticholinergic activity was associated with greater risk of
      subsequent injurious falls (adjusted relative risk (aRR) = 2.55, 95% confidence
      interval (CI) = 1.33-4.88), but the risk of having any fall and the number of
      falls reported were not significantly greater. Greater anticholinergic burden was
      associated with greater injurious falls risk. No associations were observed for
      women. Findings were similar using pharmacy dispensing records. The aRR for
      medications with definite anticholinergic activity dispensed in the month before
      baseline and subsequent injurious falls in men was 2.53 (95% CI = 1.15-5.54).
      CONCLUSION: The regular use of medications with anticholinergic activity is
      associated with subsequent injurious falls in older men, although falls were self
      reported after a 2-year recall and so may have been underreported. Further
      research is required to validate this finding in men and to consider the effect
      of duration and dose of anticholinergic medications.

PMID- 26200895
TI  - The Origin of Cultivation and Proto-Weeds, Long Before Neolithic Farming.
AB  - Weeds are currently present in a wide range of ecosystems worldwide. Although the
      beginning of their evolution is largely unknown, researchers assumed that they
      developed in tandem with cultivation since the appearance of agricultural
      habitats some 12,000 years ago. These rapidly-evolving plants invaded the human
      disturbed areas and thrived in the new habitat. Here we present unprecedented new
      findings of the presence of "proto-weeds" and small-scale trial cultivation in
      Ohalo II, a 23,000-year-old hunter-gatherers' sedentary camp on the shore of the
      Sea of Galilee, Israel. We examined the plant remains retrieved from the site
      (ca. 150,000 specimens), placing particular emphasis on the search for evidence
      of plant cultivation by Ohalo II people and the presence of weed species. The
      archaeobotanically-rich plant assemblage demonstrates extensive human gathering
      of over 140 plant species and food preparation by grinding wild wheat and barley.
      Among these, we identified 13 well-known current weeds mixed with numerous seeds
      of wild emmer, barley, and oat. This collection provides the earliest evidence of
      a human-disturbed environment-at least 11 millennia before the onset of
      agriculture-that provided the conditions for the development of "proto-weeds", a
      prerequisite for weed evolution. Finally, we suggest that their presence
      indicates the earliest, small-scale attempt to cultivate wild cereals seen in the
      archaeological record. 

PMID- 26200896
TI  - Experience of ECMO in primary graft dysfunction after orthotopic heart
      transplantation.
AB  - BACKGROUND: Primary graft dysfunction is the main cause of early mortality after
      heart transplantation. Mechanical circulatory support has been used to treat this
      syndrome. OBJECTIVE: Describe the experience with extracorporeal membrane
      oxygenation to treat post-transplant primary cardiac graft dysfunction. METHODS:
      Between January 2007 and December 2013, a total of 71 orthotopic heart
      transplantations were performed in patients with advanced heart failure. Eleven
      (15.5%) of these patients who presented primary graft dysfunction constituted the
      population of this study. Primary graft dysfunction manifested in our population
      as failure to wean from cardiopulmonary bypass in six (54.5%) patients, severe
      hemodynamic instability in the immediate postoperative period with severe cardiac
      dysfunction in three (27.3%), and cardiac arrest (18.2%). The average ischemia
      time was 151 +/- 82 minutes. Once the diagnosis of primary graft dysfunction was
      established, we installed a mechanical circulatory support to stabilize the
      severe hemodynamic condition of the patients and followed their progression
      longitudinally. RESULTS: The average duration of extracorporeal membrane
      oxygenation support was 76 +/- 47.4 hours (range 32 to 144 hours). Weaning with
      cardiac recovery was successful in nine (81.8%) patients. However, two patients
      who presented cardiac recovery did not survive to hospital discharge. CONCLUSION:
      Mechanical circulatory support with central extracorporeal membrane oxygenation
      promoted cardiac recovery within a few days in most patients.

PMID- 26200897
TI  - Testosterone deficiency increases hospital readmission and mortality rates in
      male patients with heart failure.
AB  - BACKGROUND: Testosterone deficiency in patients with heart failure (HF) is
      associated with decreased exercise capacity and mortality; however, its impact on
      hospital readmission rate is uncertain. Furthermore, the relationship between
      testosterone deficiency and sympathetic activation is unknown. OBJECTIVE: We
      investigated the role of testosterone level on hospital readmission and mortality
      rates as well as sympathetic nerve activity in patients with HF. METHODS: Total
      testosterone (TT) and free testosterone (FT) were measured in 110 hospitalized
      male patients with a left ventricular ejection fraction < 45% and New York Heart
      Association classification IV. The patients were placed into low testosterone
      (LT; n = 66) and normal testosterone (NT; n = 44) groups. Hypogonadism was
      defined as TT < 300 ng/dL and FT < 131 pmol/L. Muscle sympathetic nerve activity
      (MSNA) was recorded by microneurography in a subpopulation of 27 patients.
      RESULTS: Length of hospital stay was longer in the LT group compared to in the NT
      group (37 +/- 4 vs. 25 +/- 4 days; p = 0.008). Similarly, the cumulative hazard
      of readmission within 1 year was greater in the LT group compared to in the NT
      group (44% vs. 22%, p = 0.001). In the single-predictor analysis, TT (hazard
      ratio [HR], 2.77; 95% confidence interval [CI], 1.58-4.85; p = 0.02) predicted
      hospital readmission within 90 days. In addition, TT (HR, 4.65; 95% CI, 2.67
      8.10; p = 0.009) and readmission within 90 days (HR, 3.27; 95% CI, 1.23-8.69; p =
      0.02) predicted increased mortality. Neurohumoral activation, as estimated by
      MSNA, was significantly higher in the LT group compared to in the NT group (65 +/
      3 vs. 51 +/- 4 bursts/100 heart beats; p < 0.001). CONCLUSION: These results
      support the concept that LT is an independent risk factor for hospital
      readmission within 90 days and increased mortality in patients with HF.
      Furthermore, increased MSNA was observed in patients with LT.

PMID- 26200900
TI  - Health Information Exchange Capabilities in Skilled Nursing Facilities.
AB  - The purpose of this study is to determine the levels at which health information
      exchange is used by skilled nursing facilities for clinical functions, the
      benefits and barriers associated with health information exchange and
      telehealth/telemonitoring capabilities, and the facility characteristics
      associated with health information exchange capabilities. A cross-sectional
      design was implemented. Data were collected from nursing home administrators,
      using a mail and online survey approach. A total of 156 usable questionnaires
      were returned of 397 distributed-a 39.30% response rate. The highest level of
      electronic exchange for clinical functions was within the facility than within
      corporation/affiliated organization or with nonaffiliated providers. It was also
      more prevalent in for-profit skilled nursing facilities than nonprofit skilled
      nursing facilities. More than half of the facilities reported no electronic
      exchange for functions, such as public health reporting, diagnostic test
      orders/results, medical orders/e-prescribing, advance directives, lab
      orders/results, and radiology orders/ results. Similarly,
      telehealth/telemonitoring was not in wide use by facilities in the state. The
      greatest barriers to electronic exchange of clinical functions were financial
      barriers, technological barriers, and connectivity barriers. Faster and accurate
      billing, improved care planning, and improved quality of documentation were
      reported as benefits of electronic information exchange of clinical data with
      affiliated and nonaffiliated providers.

PMID- 26200898
TI  - Reverse auction: a potential strategy for reduction of pharmacological therapy
      cost.
AB  - BACKGROUND: Polypharmacy is a significant economic burden. OBJECTIVE: We tested
      whether using reverse auction (RA) as compared with commercial pharmacy (CP) to
      purchase medicine results in lower pharmaceutical costs for heart failure (HF)
      and heart transplantation (HT) outpatients. METHODS: We compared the costs via RA
      versus CP in 808 HF and 147 HT patients followed from 2009 through 2011, and
      evaluated the influence of clinical and demographic variables on cost. RESULTS:
      The monthly cost per patient for HF drugs acquired via RA was $10.15 (IQ 3.51
      40.22) versus $161.76 (IQ 86.05-340.15) via CP; for HT, those costs were $393.08
      (IQ 124.74-774.76) and $1,207.70 (IQ 604.48-2,499.97), respectively. CONCLUSION:
      RA may reduce the cost of prescription drugs for HF and HT, potentially making HF
      treatment more accessible. Clinical characteristics can influence the cost and
      benefits of RA. RA may be a new health policy strategy to reduce costs of
      prescribed medications for HF and HT patients, reducing the economic burden of
      treatment.

PMID- 26200899
TI  - Phosphoserine Lyase Deoxyribozymes: DNA-Catalyzed Formation of Dehydroalanine
      Residues in Peptides.
AB  - Dehydroalanine (Dha) is a nonproteinogenic electrophilic amino acid that is a
      synthetic intermediate or product in the biosynthesis of several bioactive cyclic
      peptides such as lantibiotics, thiopeptides, and microcystins. Dha also enables
      labeling of proteins and synthesis of post-translationally modified proteins and
      their analogues. However, current chemical approaches to introducing Dha into
      peptides have substantial limitations. Using in vitro selection, here we show
      that DNA can catalyze Zn(2+) or Zn(2+)/Mn(2+)-dependent formation of Dha from
      phosphoserine (pSer), i.e., exhibit pSer lyase activity, a fundamentally new DNA
      catalyzed reaction. Two new pSer lyase deoxyribozymes, named Dha-forming
      deoxyribozymes 1 and 2 (DhaDz1 and DhaDz2), each function with multiple turnover
      on the model hexapeptide substrate that was used during selection. Using DhaDz1,
      we generated Dha from pSer within an unrelated linear 13-mer peptide. Subsequent
      base-promoted intramolecular cyclization of homocysteine into Dha formed a stable
      cystathionine (thioether) analogue of the complement inhibitor compstatin. These
      findings establish the fundamental catalytic ability of DNA to eliminate
      phosphate from pSer to form Dha and suggest that with further development, pSer
      lyase deoxyribozymes will have broad practical utility for site-specific
      enzymatic synthesis of Dha from pSer in peptide substrates. 

PMID- 26200901
TI  - Emergency Department Visit Forecasting and Dynamic Nursing Staff Allocation Using
      Machine Learning Techniques With Readily Available Open-Source Software.
AB  - Although emergency department visit forecasting can be of use for nurse staff
      planning, previous research has focused on models that lacked sufficient
      resolution and realistic error metrics for these predictions to be applied in
      practice. Using data from a 1100-bed specialized care hospital with 553,000
      patients assigned to its healthcare area, forecasts with different prediction
      horizons, from 2 to 24 weeks ahead, with an 8-hour granularity, using support
      vector regression, M5P, and stratified average time-series models were generated
      with an open-source software package. As overstaffing and understaffing errors
      have different implications, error metrics and potential personnel monetary
      savings were calculated with a custom validation scheme, which simulated
      subsequent generation of predictions during a 4-year period. Results were then
      compared with a generalized estimating equation regression. Support vector
      regression and M5P models were found to be superior to the stratified average
      model with a 95% confidence interval. Our findings suggest that medium and severe
      understaffing situations could be reduced in more than an order of magnitude and
      average yearly savings of up to ?683,500 could be achieved if dynamic nursing
      staff allocation was performed with support vector regression instead of the
      static staffing levels currently in use.

PMID- 26200902
TI  - Factors Affecting Nursing Students' Readiness and Perceptions Toward the Use of
      Mobile Technologies for Learning.
AB  - The purpose of this study was to determine the current usage of mobile devices,
      preferences of mobile learning environments and examine the readiness of nursing
      students in a public university. In order to investigate preferences and
      attitudes with respect to mobile technology use in nursing education, 387
      students at a state university have been surveyed. It has been observed that
      while students preferred their current portable laptops, those in higher classes
      were more inclined to favor mobile phones. The common problems of battery life
      and high cost of communication, both in smartphones and tablet systems, suggest
      that hardware quality and financial constraints seem to be two main factors in
      determining these technologies. While more than half of students expressed
      readiness for mobile learning, one quarter indicated indecision. Through
      multivariate regression analysis, readiness to use mobile learning can be
      described in terms of perceived ease of use, perceived usefulness, personal
      innovativeness, self-management of learning, perceived device limitation, and
      availability. Class level, perceived ease of use, personal innovativeness, and
      self-management of learning explain intention to use mobile learning. Findings
      obtained from these results can provide guidance in the development and
      application of mobile learning systems. 

PMID- 26200903
TI  - Subtypes and Prognosis of Guillain-Barre Syndrome in Southwest China.
AB  - The proportion of different subtypes of Guillain-Barre syndrome (GBS) and their
      prognosis varied significantly among different regions. This study attempts to
      investigate the clinical subtypes and outcome of GBS in southwest China. Patients
      with GBS admitted to The First Affiliated Hospital of Chongqing Medical
      University from January 2006 to March 2013 were included in our study. Patients
      were classified into acute inflammatory demyelinating polyneuropathy (AIDP)
      group, acute motor axonal neuropathy (AMAN) group, Miller-Fisher syndrome (MFS)
      group, cranial nerve variants(CNV), Bickerstaff's brainstem encephalitis overlaps
      with GBS (BBE-GBS) group and unclassifiable group based on clinical features and
      electrophysiological findings. Hughes function grade score (HFGS) was used to
      assess the prognosis at 3 and 6 months. The prognosis of different subtypes and
      outcome predictors were analyzed. The most common subtype of GBS was AIDP (57%),
      followed by AMAN (22%) and MFS (7%). The prognosis of AMAN and BBE-GBS is similar
      at 3 month(P = 0.0704)and 6 month (P = 0.1614) follow-up. The prognosis of AMAN
      group was poorer than that of AIDP group at 3 month and 6 month follow-up
      (P<0.001). Outcome of MFS group and that of CNV group at 6 months were both
      good(Hughes<=1). Hughes>=3(P<0.0001,OR = 6.650,95%CI = 2.865 to 15.023))and
      dysautonomia (P = 0.043,OR = 2.820,95%CI = 1.031 to 7.715)) were associated with
      poor outcome at 6 month follow-up. AIDP is the most common subtype of GBS.
      Prognosis of AMAN group and BBE-GBS group is poorer than that of AIDP group at 3
      month and 6 month follow-up. Hughes>=3 at nadir and dysautonomia are predictors
      of poor prognosis at 6 month follow-up. 

PMID- 26200904
TI  - External Validation of a Referral Rule for Axial Spondyloarthritis in Primary
      Care Patients with Chronic Low Back Pain.
AB  - OBJECTIVES: To validate and optimize a referral rule to identify primary care
      patients with chronic low back pain (CLBP) suspected for axial spondyloarthritis
      (axSpA). DESIGN: Cross-sectional study with data from 19 Dutch primary care
      practices for development and 38 for validation. PARTICIPANTS: Primary care
      patients aged 18-45 years with CLBP existing more than three months and onset of
      back pain started before the age of 45 years. MAIN OUTCOME: The number of axSpA
      patients according to the ASAS criteria. METHODS: The referral rule (CaFaSpA
      referral rule) was developed using 364 CLBP patients from 19 primary care
      practices and contains four easy to use variables; inflammatory back pain, good
      response to nonsteriodal anti-inflammatory drugs, family history of
      spondyloarthritis and a back pain duration longer than five years. This referral
      rule is positive when at least two variables are present. Validation of the
      CaFaSpA rule was accomplished in 579 primary care CLBP patients from 38 practices
      from other areas. Performance of the referral rule was assessed by c-statistic
      and calibration plot. To fit the final referral rule the development and
      validation datasets were pooled leading to a total study population of 943
      primary care participants. RESULTS: The referral rule was validated in 579
      patients (41% male, mean age 36 (sd7.0). The percentage of identified axSpA
      patients was 16% (n=95). External validation resulted in satisfactory calibration
      and reasonable discriminative ability (c-statistics 0.70 [95% CI, 0.64-0.75]). In
      the pooled dataset sensitivity and specificity of the referral rule were 75% and
      58%. CONCLUSIONS: The CaFaSpA referral rule for axSpA consists of four easy to
      use predictors for primary care physicians and has a good predictive value in
      this validation study. The referral rule has the potential to be a screening tool
      for primary care by identifying CLBP patients suspected for axSpA.

PMID- 26200905
TI  - Predictive and Prognostic Value of Ribonucleotide Reductase Regulatory Subunit M1
      and Excision Repair Cross-Complementation Group 1 in Advanced Urothelial
      Carcinoma (UC) Treated with First-Line Gemcitabine Plus Platinum Combination
      Chemotherapy.
AB  - Preclinical and clinical studies have suggested that expression of ribonucleotide
      reductase regulatory subunit M1 (RRM1) and excision repair cross-complementation
      group 1 (ERCC1) is associated with resistance to gemcitabine and cisplatin,
      respectively. We evaluated the significance of RRM1 and ERCC1 expression to
      predict tumor response to gemcitabine plus platinum chemotherapy (GP) and
      survival in advanced UC. We retrospectively collected tumor samples and reviewed
      clinical data of 53 patients with unresectable or metastatic UC, who were treated
      with first-line GP. RRM1 and ERCC1 expression were measured by
      immunohistochemistry. Among 53 patients, 12 (22.6%) and 26 (49.1%) patients had
      tumors that demonstrated a high expression for RRM1 and ERCC1, respectively.
      Twenty-nine (70.7%) of 41 patients with low RRM1 expression achieved a clinical
      response (complete + partial responses), but only 3 (25.0%) of 12 patients with
      high RRM1 expression achieved a clinical response after GP (P=0.007). Nineteen
      (70.4%) of 27 patients with low ERCC1 expression achieved a clinical response,
      while 13 (50.0%) of 26 patients with high ERCC1 expression achieved a clinical
      response (P=0.130). High RRM1 expression was associated with shorter progression
      free survival and overall survival (PFS P=0.006, OS P=0.006). Multivariate
      analysis confirmed that patients with high RRM1 expression had a significantly
      greater risk of progression and death than those with low RRM1 expression. ERCC1
      status was not a significant predictor for PFS and OS. RRM1 expression was
      predictive and prognostic of clinical outcome in advanced UC treated with
      gemcitabine plus platinum combination chemotherapy. 

PMID- 26200907
TI  - An Efficient One-Pot Approach to the Construction of Chiral Nitrogen-Containing
      Heterocycles under Mild Conditions.
AB  - A new, general, and practical procedure for the highly enantioselective synthesis
      of functionalized nitrogen-containing heterocycles has been developed. The simple
      cyclic hemiaminals were directly catalyzed for the first time as nucleophiles in
      an enamine-based asymmetric conjugate addition reaction. The practical approach
      recycles the catalyst and solvent which make it possible for large-scale and
      diversity-oriented chemical production. 

PMID- 26200906
TI  - Biophysical Assessment and Predicted Thermophysiologic Effects of Body Armor.
AB  - INTRODUCTION: Military personnel are often required to wear ballistic protection
      in order to defend against enemies. However, this added protection increases mass
      carried and imposes additional thermal burden on the individual. Body armor (BA)
      is known to reduce combat casualties, but the effects of BA mass and insulation
      on the physical performance of soldiers are less well documented. Until recently,
      the emphasis has been increasing personal protection, with little consideration
      of the adverse impacts on human performance. OBJECTIVE: The purpose of this work
      was to use sweating thermal manikin and mathematical modeling techniques to
      quantify the tradeoff between increased BA protection, the accompanying mass, and
      thermal effects on human performance. METHODS: Using a sweating thermal manikin,
      total insulation (IT, clo) and vapor permeability indexes (im) were measured for
      a baseline clothing ensemble with and without one of seven increasingly
      protective U.S. Army BA configurations. Using mathematical modeling, predictions
      were made of thermal impact on humans wearing each configuration while working in
      hot/dry (desert), hot/humid (jungle), and temperate environmental conditions.
      RESULTS: In nearly still air (0.4 m/s), IT ranged from 1.57 to 1.63 clo and im
      from 0.35 to 0.42 for the seven BA conditions, compared to IT and im values of
      1.37 clo and 0.45 respectively, for the baseline condition (no BA). CONCLUSION:
      Biophysical assessments and predictive modeling show a quantifiable relationship
      exists among increased protection and increased thermal burden and decreased work
      capacity. This approach enables quantitative analysis of the tradeoffs between
      ballistic protection, thermal-work strain, and physical work performance.

PMID- 26200908
TI  - Toward a biomarker of oxidative stress: a fluorescent probe for exogenous and
      endogenous malondialdehyde in living cells.
AB  - Malondialdehyde (MDA) is a significant biomarker of oxidative stress. Variations
      of MDA level in biological systems often represent pathological changes that are
      related with many types of diseases. Although a variety of techniques have been
      developed for MDA detection, the probing of this biomarker in living cells
      remains unexplored. Herein, we report a turn-on fluorescent probe, MDAP-1, with a
      synergistic photoinduced electron transfer (PET)-hydrogen bonding mechanism,
      which for the first time realizes MDA sensing under physiological conditions with
      excellent sensitivity and specificity. The probe responds to MDA with a
      fluorescence enhancement factor (FEF) of up to >170-fold and a large Stokes shift
      (~180 nm). Further biological evaluations show that MDAP-1 is able to detect both
      endogenous and exogenous MDA in living cells. It can be used to track the
      generation of MDA under oxidative stress, as stimulated by H2O2. We believe the
      results of this work will be helpful to the studies of MDA-related biological
      events and the elucidation of the underlying pathological mechanism in the
      future. 

PMID- 26200909
TI  - Author's Response.

PMID- 26200911
TI  - A recognition-before-labeling strategy for sensitive detection of lung cancer
      cells with a quantum dot-aptamer complex.
AB  - A highly specific recognition-before-labeling strategy has been developed for
      sensitive detection of non-small cell lung cancer A549 cells, by using
      fluorescent QDs as signal units and DNA aptamers as recognition elements. A QD
      aptamer system used for cell imaging and bioanalysis mostly relies on the
      recognition-after-labeling strategy in which aptamers were firstly labeled with
      QDs and then the QD-aptamer conjugates as a whole were utilized for specific
      recognition. Here in our strategy, aptamers were used firstly to recognize target
      cells, and then fluorescent QDs were sequentially added to bind the aptamers and
      light the target cells. The proposed recognition-before-labeling strategy didn't
      require the complex process of QD functionalization, and avoided the possible
      impact on the aptamer configuration from steric hindrance. Meanwhile, QDs, with
      strong fluorescence and good photostability, also give this method a high signal
      to-background ratio (S/B). The recognition-before-labeling strategy is simple and
      sensitive, suggesting a new method for in vitro diagnostic assays of cancer
      cells. 

PMID- 26200910
TI  - Analysis of the SUMO2 Proteome during HSV-1 Infection.
AB  - Covalent linkage to members of the small ubiquitin-like (SUMO) family of proteins
      is an important mechanism by which the functions of many cellular proteins are
      regulated. Sumoylation has roles in the control of protein stability, activity
      and localization, and is involved in the regulation of transcription, gene
      expression, chromatin structure, nuclear transport and RNA metabolism.
      Sumoylation is also linked, both positively and negatively, with the replication
      of many different viruses both in terms of modification of viral proteins and
      modulation of sumoylated cellular proteins that influence the efficiency of
      infection. One prominent example of the latter is the widespread reduction in the
      levels of cellular sumoylated species induced by herpes simplex virus type 1 (HSV
      1) ubiquitin ligase ICP0. This activity correlates with relief from intrinsic
      immunity antiviral defence mechanisms. Previous work has shown that ICP0 is
      selective in substrate choice, with some sumoylated proteins such the
      promyelocytic leukemia protein PML being extremely sensitive, while RanGAP is
      completely resistant. Here we present a comprehensive proteomic analysis of
      changes in the cellular SUMO2 proteome during HSV-1 infection. Amongst the 877
      potentially sumoylated species detected, we identified 124 whose abundance was
      decreased by a factor of 3 or more by the virus, several of which were validated
      by western blot and expression analysis. We found many previously undescribed
      substrates of ICP0 whose degradation occurs by a range of mechanisms, influenced
      or not by sumoylation and/or the SUMO2 interaction motif within ICP0. Many of
      these proteins are known or are predicted to be involved in the regulation of
      transcription, chromatin assembly or modification. These results present novel
      insights into mechanisms and host cell proteins that might influence the
      efficiency of HSV-1 infection. 

PMID- 26200912
TI  - Impact of Age on Short-term Outcomes After Lumbar Fusion: An Analysis of 1395
      Patients Stratified by Decade Cohorts.
AB  - BACKGROUND: The safety and efficacy of spinal fusion in the elderly population
      remains uncertain with conflicting data. OBJECTIVE: To determine if elderly
      patients undergoing instrumented lumbar fusion have increased 30-day complication
      rates compared to younger patients. METHODS: The American College of Surgeons
      National Surgical Quality Improvement Program was used to identify all patients
      undergoing instrumented posterolateral lumbar fusion between 2005 and 2011.
      Patients were stratified by decade cohorts as follows: <65, 65 to 75, 75 to 85,
      and >=85 years old. All 30-day complications were grouped as overall composite
      morbidity and were compared using multivariate analysis. RESULTS: A total of 1395
      patients were identified and the overall 30-day complication rate was 11.47%. The
      complication rates were 9.04% and 14.05% for patients younger than 65 and older
      than 65, respectively. When stratified by decade cohorts, the complication rates
      were 9.04% for the <65 cohort, 13.46% for the 65 to 75 cohort, 16.17% for the >75
      to 85 cohort, and 4.00% for the >=85 cohort. Multivariable regression analysis
      revealed no statistically significant difference between the <65 and >=65 age
      cohorts (odds ratio = 1.26; 95% confidence interval: 0.87-2.19). After
      stratifying into age cohorts, multivariable analyses revealed no difference in
      odds of postoperative complication occurrence for any age cohort when compared
      with the referent group (<65 years of age). CONCLUSION: Patients older than 65
      years of age have significantly higher rates of complications after lumbar fusion
      when compared to younger patients. However, multivariable analysis revealed that
      age was not an independent risk factor for complication occurrence after lumbar
      fusion.

PMID- 26200913
TI  - Projection of Diabetes Population Size and Associated Economic Burden through
      2030 in Iran: Evidence from Micro-Simulation Markov Model and Bayesian Meta
      Analysis.
AB  - BACKGROUND: The aim of this study was to estimate the economic burden of diabetes
      mellitus (DM) in Iran from 2009 to 2030. METHODS: A Markov micro-simulation (MM)
      model was developed to predict the DM population size and associated economic
      burden. Age- and sex-specific prevalence and incidence of diagnosed and
      undiagnosed DM were derived from national health surveys. A systematic review was
      performed to identify the cost of diabetes in Iran and the mean annual direct and
      indirect costs of patients with DM were estimated using a random-effect Bayesian
      meta-analysis. Face, internal, cross and predictive validity of the MM model were
      assessed by consulting an expert group, performing sensitivity analysis (SA) and
      comparing model results with published literature and national survey reports.
      Sensitivity analysis was also performed to explore the effect of uncertainty in
      the model. RESULTS: We estimated 3.78 million cases of DM (2.74 million diagnosed
      and 1.04 million undiagnosed) in Iran in 2009. This number is expected to rise to
      9.24 million cases (6.73 million diagnosed and 2.50 million undiagnosed) by 2030.
      The mean annual direct and indirect costs of patients with DM in 2009 were US$
      556 (posterior standard deviation, 221) and US$ 689 (619), respectively. Total
      estimated annual cost of DM was $3.64 (2009 US$) billion (including US$1.71
      billion direct and US$1.93 billion indirect costs) in 2009 and is predicted to
      increase to $9.0 (in 2009 US$) billion (including US$4.2 billion direct and
      US$4.8 billion indirect costs) by 2030. CONCLUSIONS: The economic burden of DM in
      Iran is predicted to increase markedly in the coming decades. Identification and
      implementation of effective strategies to prevent and manage DM should be
      considered as a public health priority.

PMID- 26200916
TI  - International Association for Suicide Prevention.

PMID- 26200914
TI  - Phylogeny of Dictyoptera: Dating the Origin of Cockroaches, Praying Mantises and
      Termites with Molecular Data and Controlled Fossil Evidence.
AB  - Understanding the origin and diversification of organisms requires a good
      phylogenetic estimate of their age and diversification rates. This estimate can
      be difficult to obtain when samples are limited and fossil records are disputed,
      as in Dictyoptera. To choose among competing hypotheses of origin for
      dictyopteran suborders, we root a phylogenetic analysis (~800 taxa, 10 kbp)
      within a large selection of outgroups and calibrate datings with fossils
      attributed to lineages with clear synapomorphies. We find the following topology:
      (mantises, (other cockroaches, (Cryptocercidae, termites)). Our datings suggest
      that crown-Dictyoptera-and stem-mantises-would date back to the Late
      Carboniferous (~ 300 Mya), a result compatible with the oldest putative fossil of
      stem-dictyoptera. Crown-mantises, however, would be much more recent (~ 200 Mya;
      Triassic/Jurassic boundary). This pattern (i.e., old origin and more recent
      diversification) suggests a scenario of replacement in carnivory among
      polyneopterous insects. The most recent common ancestor of (cockroaches +
      termites) would date back to the Permian (~275 Mya), which contradicts the
      hypothesis of a Devonian origin of cockroaches. Stem-termites would date back to
      the Triassic/Jurassic boundary, which refutes a Triassic origin. We suggest
      directions in extant and extinct species sampling to sharpen this chronological
      framework and dictyopteran evolutionary studies. 

PMID- 26200917
TI  - In vivo proton magnetic resonance spectroscopy of liver metabolites in non
      alcoholic fatty liver disease in rats: T2 relaxation times in methylene protons.
AB  - The aim of this study was to evaluate the transverse relaxation time of methylene
      resonance as compared to other lipid resonances. The examinations were performed
      using a 3.0 T scanner with a point-resolved spectroscopy (PRESS) sequence. Lipid
      relaxation time in a lipid phantom filled with canola oil was estimated with a
      repetition time (TR) of 6000ms and echo time (TE) of 40-550ms. For in vivo proton
      magnetic resonance spectroscopy ((1)H-MRS), eight male Sprague-Dawley rats were
      given free access to a normal-chow (NC) and another eight male Sprague-Dawley
      rats were given free access to a high-fat (HF) diet. Both groups drank water ad
      libitum. T2 measurements in the rats' livers were conducted at a fixed TR of
      6000ms and TE of 40-220ms. Exponential curve fitting quality was calculated
      through the coefficients of determination (R(2)). Chemical analyses of the
      phantom and livers were not performed, but T2 decay curves were acquired. The T2
      relaxation time of methylene resonance was estimated as follows: NC rats, 37.1+/
      4.3ms; HF rats, 31.4+/-1.8ms (p<0.05). The extrapolated M0 values were higher in
      HF rats than in NC rats (p<0.005). This study of (1)H MRS led to sufficient
      spectral resolution and signal-to-noise ratio differences to characterize the T2
      relaxation times of methylene resonance. (1)H MRS relaxation times may be useful
      for quantitative characterization of various liver diseases, including fatty
      liver disease. 

PMID- 26200918
TI  - Inhibitors of the sphingomyelin cycle: Sphingomyelin synthases and
      sphingomyelinases.
AB  - Sphingolipids are a class of bioactive lipids, which are key modulators of an
      increasing number of physiologic and pathophysiologic processes that include cell
      cycle, apoptosis, angiogenesis, stress and inflammatory responses. Sphingomyelin
      is an important structural component of biological membranes, and one of the end
      points in the synthesis of sphingolipids. Mainly synthetized in the Golgi
      apparatus, sphingomyelin is transported to all other biological membranes. Upon
      stimulation, sphingomyelin can be hydrolyzed to ceramide by 5 different
      sphingomyelinases. The diversity and cellular topology of ceramide allow it to
      exert multiple biologies. Furthermore, ceramide can be metabolized to many other
      bioactive sphingolipids. Ceramide, coming from sphingomyelin or other complex
      sphingolipids, can be hydrolyzed to sphingosine, which can easily change cellular
      localization. In turn, sphingosine can be recycled to ceramide and to
      sphingomyelin in the endoplasmic reticulum, completing the sphingomyelin cycle.
      Our understanding of the roles of various sphingolipids in the regulation of
      different cellular processes has come from studying the enzymes that regulate
      these sphingolipids, and their manipulation. The use of pharmacologic inhibitors
      has been critical for their study, as well as being promising bullets for disease
      treatment. Some of these diseases involving the sphingomyelin cycle include
      cancer, inflammation, atherosclerosis, diabetes and some rare diseases such as
      Niemann-Pick disease. This review will focus on the enzymes involved in the
      sphingomyelin cycle, their history, and their involvement in pathophysiological
      processes. Finally, it will describe in details all the small molecules that are
      being used to inhibit these enzymes and their use in therapeutics. 

PMID- 26200919
TI  - Inhibitors of sphingosine-1-phosphate metabolism (sphingosine kinases and
      sphingosine-1-phosphate lyase).
AB  - Sphingolipids (SLs) are essential structural and signaling molecules of
      eukaryotic cells. Among them, sphingosine 1 phosphate (S1P) is a recognized
      promoter of cell survival, also involved, inter alia, in inflammation and
      tumorigenesis processes. The knowledge and modulation of the enzymes implicated
      in the biosynthesis and degradation of S1P are capital to control the
      intracellular levels of this lipid and, ultimately, to determine the cell fate.
      Starting with a general overview of the main metabolic pathways involved in SL
      metabolism, this review is mainly focused on the description of the most relevant
      findings concerning the development of modulators of S1P, namely inhibitors of
      the enzymes regulating S1P synthesis (sphingosine kinases) and degradation
      (sphingosine 1 phosphate phosphatase and lyase). In addition, a brief overview of
      the most significant agonists and antagonists at the S1P receptors is also
      addressed. 

PMID- 26200921
TI  - AgPO2F2 and Ag9(PO2F2)14: the first Ag(i) and Ag(i)/Ag(ii) difluorophosphates
      with complex crystal structures.
AB  - The reaction of AgF2 with P2O3F4 yields a mixed valence Ag(I)/Ag(II)
      difluorophosphate salt with AgAg(PO2F2)14 stoichiometry - the first Ag(ii)-PO2F2
      system known. This highly moisture sensitive brown solid is thermally stable up
      to 120  degrees C, which points at further feasible extension of the chemistry of
      Ag(ii)-PO2F2 systems. The crystal structure shows a very complex bonding pattern,
      comprising of polymeric Ag(PO2F2)14(4-) anions and two types of Ag(I) cations.
      One particular Ag(II) site present in the crystal structure of Ag9(PO2F2)14 is
      the first known example of square pyramidal penta-coordinated Ag(ii) in an oxo
      ligand environment. Ag(i)PO2F2 - the product of the thermal decomposition of
      Ag9(PO2F2)14 - has also been characterized by thermal analysis, IR spectroscopy
      and X-ray powder diffraction. It has a complicated crystal structure as well,
      which consists of infinite 1D [Ag(I)O4/2] chains which are linked to more complex
      3D structures via OPO bridges. The PO2F2(-) anions bind to cations in both
      compounds as bidentate oxo-ligands. The terminal F atoms tend to point inside the
      van der Waals cavities in the crystal structure of both compounds. All important
      structural details of both title compounds were corroborated by DFT calculations.

PMID- 26200920
TI  - Synthesis and photochemical properties of PEGylated coumarin-caged ceramides for
      cell studies.
AB  - Caged ceramide analogues (C6-, C16-, C18-, C22- and C24-Cer) have been prepared
      by introducing a hydrophilic coumarin-based cage bearing a short polyethylene
      glycol (PEG) chain. (6-Bromo-7-mTEGylated-coumarin-4-yl)methyl (Btc) caged
      ceramide showed efficient photo-uncaging to release the parent ceramide upon
      direct exposure to 350 nm UV light; in contrast (7-mTEGylated-coumarin-4
      yl)methyl (Tc) caged ceramide was photolysed more slowly. In preliminary
      experiments, Btc-caged ceramides were taken up by cells and their photolysis led
      to decreases in cell viability, but not to activation of caspase enzymes,
      suggesting that either reactive oxygen species or an alternate caspase
      independent pathway may be responsible for the decreases in cell viability caused
      by photolysis of caged ceramides.

PMID- 26200922
TI  - Functionally redundant but dissimilar microbial communities within biogas
      reactors treating maize silage in co-fermentation with sugar beet silage.
AB  - Numerous observations indicate a high flexibility of microbial communities in
      different biogas reactors during anaerobic digestion. Here, we describe the
      functional redundancy and structural changes of involved microbial communities in
      four lab-scale continuously stirred tank reactors (CSTRs, 39 degrees C, 12 L
      volume) supplied with different mixtures of maize silage (MS) and sugar beet
      silage (SBS) over 80 days. Continuously stirred tank reactors were fed with
      mixtures of MS and SBS in volatile solid ratios of 1:0 (Continuous Fermenter (CF)
      1), 6:1 (CF2), 3:1 (CF3), 1:3 (CF4) with equal organic loading rates (OLR 1.25
      kgVS m(-3)  d(-1) ) and showed similar biogas production rates in all reactors.
      The compositions of bacterial and archaeal communities were analysed by 454
      amplicon sequencing approach based on 16S rRNA genes. Both bacterial and archaeal
      communities shifted with increasing amounts of SBS. Especially pronounced were
      changes in the archaeal composition towards Methanosarcina with increasing
      proportion of SBS, while Methanosaeta declined simultaneously. Compositional
      shifts within the microbial communities did not influence the respective biogas
      production rates indicating that these communities adapted to environmental
      conditions induced by different feedstock mixtures. The diverse microbial
      communities optimized their metabolism in a way that ensured efficient biogas
      production. 

PMID- 26200923
TI  - Versatile Coordination Mode of a New Pyridine-Based Ditopic Ligand with
      Transition Metals: From Regular Pyridine to Alkyne and Alkenyl Bindings and
      Indolizinium Formation.
AB  - The new BPMPB ligand, namely, bis[1-bis(2-pyridylmethyl),1 (pyridyl)]butyne, can
      be very easily obtained as a side product in the known reaction of picolyl
      chloride and sodium acetylide (which major product is the known terminal alkyne
      substituted tripod). This symmetrical ligand contains two identical coordination
      sites with two methylenepyridines and one pyridyl group on each side, linked by
      an alkyne function providing a semirigid segment. Together with the molecular
      structure of the ligand which is reported, we describe the preparation of
      complexes with Fe(II)Cl2, Co(II)Cl2, Ni(II)Cl2, Cu(I)Cl, and Zn(II)Cl2 salts. All
      complexes have been characterized by X-ray diffraction studies as well as by
      standard spectroscopic techniques. The striking point in this work is the
      diversity of the structures that are obtained. Co(II) and Zn(II) provide
      isostructural dinuclear complexes in which both coordination sites are occupied
      within a tetrahedral symmetry. The Cu(I) complex is also a dinuclear compound,
      but in that case, the copper atom is coordinated to the alkyne moiety, two
      pyridines, and a bridging chloride. The (13)C NMR spectrum of the copper complex
      confirms that the metal center is coordinated to the alkyne in solution. The
      coordination of Ni(II) results in the formation of a mononuclear complex in which
      a pyridine has fused with the alkyne moiety to generate an indolizinium group;
      the structure of the corresponding alkenyl complex is reported. Finally, the
      addition of FeCl2 to the ligand results in the formation of a mononuclear complex
      with a free, noncoordinated indolizinium. The sequence developed in the present
      work illustrates the possibility for the metal centers to adopt various
      coordination modes which may be relevant to the conversion of an alkyne and a
      pyridyl unit into indolizinium. 

PMID- 26200925
TI  - Direct and post-synthesis incorporation of chiral metallosalen catalysts into
      metal-organic frameworks for asymmetric organic transformations.
AB  - Two chiral porous metal-organic frameworks (MOFs) were constructed from
      [VO(salen)]-derived dicarboxylate and dipyridine bridging ligands. After
      oxidation of V(IV) to V(V) , they were found to be highly effective, recyclable,
      and reusable heterogeneous catalysts for the asymmetric cyanosilylation of
      aldehydes with up to 95 % ee. Solvent-assisted linker exchange (SALE) treatment
      of the pillared-layer MOF with [Cr(salen)Cl]- or [Al(salen)Cl]-derived dipyridine
      ligands led to the formation of mixed-linker metallosalen-based frameworks and
      incorporation of [Cr(salen)] enabled its use as a heterogeneous catalyst in the
      asymmetric epoxide ring-opening reaction. 

PMID- 26200924
TI  - Timing and Variability of Galactose Metabolic Gene Activation Depend on the Rate
      of Environmental Change.
AB  - Modulation of gene network activity allows cells to respond to changes in
      environmental conditions. For example, the galactose utilization network in
      Saccharomyces cerevisiae is activated by the presence of galactose but repressed
      by glucose. If both sugars are present, the yeast will first metabolize glucose,
      depleting it from the extracellular environment. Upon depletion of glucose, the
      genes encoding galactose metabolic proteins will activate. Here, we show that the
      rate at which glucose levels are depleted determines the timing and variability
      of galactose gene activation. Paradoxically, we find that Gal1p, an enzyme needed
      for galactose metabolism, accumulates more quickly if glucose is depleted slowly
      rather than taken away quickly. Furthermore, the variability of induction times
      in individual cells depends non-monotonically on the rate of glucose depletion
      and exhibits a minimum at intermediate depletion rates. Our mathematical modeling
      suggests that the dynamics of the metabolic transition from glucose to galactose
      are responsible for the variability in galactose gene activation. These findings
      demonstrate that environmental dynamics can determine the phenotypic outcome at
      both the single-cell and population levels. 

PMID- 26200926
TI  - Background Noise Degrades Central Auditory Processing in Toddlers.
AB  - OBJECTIVES: Noise, as an unwanted sound, has become one of modern society's
      environmental conundrums, and many children are exposed to higher noise levels
      than previously assumed. However, the effects of background noise on central
      auditory processing of toddlers, who are still acquiring language skills, have so
      far not been determined. The authors evaluated the effects of background noise on
      toddlers' speech-sound processing by recording event-related brain potentials.
      The hypothesis was that background noise modulates neural speech-sound encoding
      and degrades speech-sound discrimination. DESIGN: Obligatory P1 and N2 responses
      for standard syllables and the mismatch negativity (MMN) response for five
      different syllable deviants presented in a linguistic multifeature paradigm were
      recorded in silent and background noise conditions. The participants were 18
      typically developing 22- to 26-month-old monolingual children with healthy ears.
      RESULTS: The results showed that the P1 amplitude was smaller and the N2
      amplitude larger in the noisy conditions compared with the silent conditions. In
      the noisy condition, the MMN was absent for the intensity and vowel changes and
      diminished for the consonant, frequency, and vowel duration changes embedded in
      speech syllables. Furthermore, the frontal MMN component was attenuated in the
      noisy condition. However, noise had no effect on P1, N2, or MMN latencies.
      CONCLUSIONS: The results from this study suggest multiple effects of background
      noise on the central auditory processing of toddlers. It modulates the early
      stages of sound encoding and dampens neural discrimination vital for accurate
      speech perception. These results imply that speech processing of toddlers, who
      may spend long periods of daytime in noisy conditions, is vulnerable to
      background noise. In noisy conditions, toddlers' neural representations of some
      speech sounds might be weakened. Thus, special attention should be paid to
      acoustic conditions and background noise levels in children's daily environments,
      like day-care centers, to ensure a propitious setting for linguistic development.
      In addition, the evaluation and improvement of daily listening conditions should
      be an ordinary part of clinical intervention of children with linguistic
      problems.

PMID- 26200927
TI  - Large thrombus entrapped in a patent foramen ovale complicated by stroke and
      pulmonary embolism.

PMID- 26200928
TI  - Functional and Neuroanatomic Specificity of Episodic Memory Dysfunction in
      Schizophrenia: A Functional Magnetic Resonance Imaging Study of the Relational
      and Item-Specific Encoding Task.
AB  - IMPORTANCE: Individuals with schizophrenia can encode item-specific information
      to support familiarity-based recognition but are disproportionately impaired
      encoding interitem relationships (relational encoding) and recollecting
      information. The Relational and Item-Specific Encoding (RiSE) paradigm has been
      used to disentangle these encoding and retrieval processes, which may depend on
      specific medial temporal lobe (MTL) and prefrontal cortex (PFC) subregions.
      Functional magnetic resonance (fMRI) imaging during RiSE task performance could
      help to specify dysfunctional neural circuits in schizophrenia that can be
      targeted for interventions to improve memory and functioning in the illness.
      OBJECTIVES: To use fMRI to test the hypothesis that schizophrenia
      disproportionately affects MTL and PFC subregions during relational encoding and
      retrieval relative to item-specific memory processes, and to use fMRI results
      from healthy individuals serving as controls to establish neural construct
      validity for RiSE. DESIGN, SETTING, AND PARTICIPANTS: This multisite, case
      control, cross-sectional fMRI study was conducted between November 1, 2010, and
      May 30, 2012, at 5 Cognitive Neuroscience Test Reliability and Clinical
      Applications for Schizophrenia sites. The final sample included 52 outpatients
      with clinically stable schizophrenia and 57 demographically matched healthy
      control participants. Data analysis was performed between February 1, 2013, and
      May 30, 2014. MAIN OUTCOMES AND MEASURES: Behavioral performance speed and
      accuracy (d') on item recognition and associative recognition tasks. Voxelwise
      statistical parametric maps for a priori MTL and PFC regions of interest to test
      activation differences between relational and item-specific memory during
      encoding and retrieval. RESULTS: Item recognition was disproportionately impaired
      in patients with schizophrenia relative to healthy control participants following
      relational encoding (F1,107 = 4.7; P = .03). The differential deficit was
      accompanied by reduced dorsolateral PFC activation during relational encoding in
      patients with schizophrenia compared with healthy control participants (z > 2.3;
      P < .05 corrected). Retrieval success (hits > misses) was associated with
      hippocampal activation in healthy control participants during relational item
      recognition and associative recognition conditions, and hippocampal activation
      was specifically reduced in schizophrenia for recognition of relational but not
      item-specific information (z > 2.3; P < .05 corrected). CONCLUSIONS AND
      RELEVANCE: In this unique, multisite fMRI study, results in the healthy control
      group supported RiSE construct validity by revealing expected memory effects in
      PFC and MTL subregions during encoding and retrieval. Comparison of schizophrenic
      and healthy control participants revealed disproportionate memory deficits in
      schizophrenia for relational vs item-specific information, accompanied by
      regionally and functionally specific deficits in dorsolateral PFC and hippocampal
      activation.

PMID- 26200929
TI  - Infliximab in ulcerative colitis: real-life analysis of factors predicting
      treatment discontinuation due to lack of response or colectomy: ECIA (ACAD
      Colitis and Infliximab Study).
AB  - OBJECTIVE: To describe clinical practice with infliximab (IFX) in ulcerative
      colitis (UC); identification of predictive factors for IFX treatment
      discontinuation due to insufficient response and for colectomy. MATERIAL AND
      METHODS: Retrospective, multicentric and observational study including every UC
      IFX-treated patient in 10 Spanish hospitals. Variables analyzed: epidemiological
      data; variables for poor prognosis; IFX prior treatments; characteristics of the
      IFX treatment; time from the UC diagnosis to induction with IFX; time from
      induction to colectomy or until data collection. Predictive and protective
      factors for IFX discontinuation due to lack of response and for colectomy were
      analyzed with binary logistic regression and Cox analysis. RESULTS: Follow-up
      time from induction with IFX to the collection of data or colectomy: 36.7 +/-
      25.7 months. Prior treatment with immunomodulator medications (IMM): 79%; IFX +
      immunosuppressant therapy: 77%; discontinuation of IFX: 26%, colectomy 16%.
      Independent predictive or protective factors for IFX discontinuation: IMM
      resistance (OR: 2.9, p = 0.022, 95% CI: 1.2-7.2), prior use of leukocytapheresis
      (OR: 3.3, p = 0.024, 95% CI: 1.1-9.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95%
      CI: 0.1-0.9, and HR: 0.4, p = 0.006, 95% CI: 0.2-0.8) and corticosteroid use in
      induction (HR: 1.9, p = 0.049, 95% CI: 1.0-3.8). Independent predictive or
      protective factors for colectomy: Use of leukocytapheresis (OR: 3.0, p = 0.036,
      95% CI: 1.1-8.4), IFX + IMM therapy (OR: 0.3, p = 0.022, 95% CI: 0.1-0.8, and HR:
      0.3, p = 0.011, 95% CI: 0.1-0.8) and severe cortico-resistant flare-up (HR: 2.5,
      p = 0.032, 95% CI: 1.1-5.9). CONCLUSIONS: Prior use of IMM and leukocytapheresis,
      the use of corticosteroids in induction and a severe cortico-resistant flare
      predict a worse response to IFX and the need for colectomy. Combination therapy
      is a protective factor for both.

PMID- 26200931
TI  - Sustainable nanotechnology.

PMID- 26200930
TI  - Physical Activity and Amyloid-beta Brain Levels in Elderly Adults with Intact
      Cognition and Mild Cognitive Impairment.
AB  - OBJECTIVES: To examine the associations between amyloid-beta brain deposition and
      physical activity (PA) in elderly adults without dementia and to investigate
      whether the association has a dose-response relationship. DESIGN: Cross-sectional
      study. SETTING: French community-dwelling people. PARTICIPANTS: Elderly adults
      with normal or mildly impaired cognition (mean age 74.7 +/- 4.2; 60.4% female)
      with available information on current self-reported PA and amyloid-beta brain
      deposition measured using positron emission tomography (PET) using the PET-ligand
      florbetapir F 18 (n = 268). MEASUREMENTS: A standardized uptake value ratio
      (SUVR) was obtained for each subject. Participants were divided according to
      amyloid plaque cortical retention defined according to a SUVR cutoff of 1.10
      (SUVR+ vs SUVR-). RESULTS: Bivariate and multivariate analyses showed that PA was
      not significantly associated with SUVR. SUVR+ and SUVR- participants did not
      differ in terms of volume (continuous PA variables) and levels (categorical PA
      variables) of PA. PA was not correlated with SUVR in apolipoprotein E epsilon4
      carriers or noncarriers. PA was not associated with cognitive function.
      CONCLUSION: Although PA protects against dementia, there is no solid evidence
      that this protection involves a reduction in amyloid-beta brain deposition.
      Further studies are needed to determine whether PA (ideally measured at several
      time-points using objective measures) is involved in the pathophysiology of
      Alzheimer's disease.

PMID- 26200934
TI  - Realization of ppb-Scale Toluene-Sensing Abilities with Pt-Functionalized SnO2
      ZnO Core-Shell Nanowires.
AB  - In this paper, we report the exceptional toluene-sensing properties of SnO2-ZnO
      core-shell nanowires (C-S NWs) functionalized with Pt nanoparticles (NPs). A
      response of 279 was obtained for 100 ppb of toluene, and to the best of our
      knowledge, this is the highest toluene response to be reported in the literature.
      The SnO2-ZnO C-S NWs were synthesized via a two-step process: First, a networked
      core of SnO2 nanowires was prepared via vapor-liquid-solid growth on the
      patterned electrode layer. Second, the ZnO shell layers were created with atomic
      layer deposition. The electron-depleted region of the shell layer was further
      expanded by attaching Pt NPs, which were synthesized using gamma-ray radiolysis,
      to the shell layer. In addition to the expansion of the electron-depleted region,
      the catalytic effect of Pt on toluene greatly improved the toluene-sensing
      performance of the C-S NWs. The extraordinary toluene-sensing ability of the Pt
      functionalized C-S NWs means they have great potential as the sensing platform in
      exhaled breath sensors to detect ppb-scale toluene. 

PMID- 26200933
TI  - Lipoarabinomannan-specific TNF-alpha and IFN-gamma as markers of protective
      immunity against tuberculosis: a cohort study in an endemic setting.
AB  - Lipoarabinomannan (LAM) is a virulent factor used for entry and survival of
      Mycobacterium tuberculosis (Mtb) in macrophages. Although the role of LAM for the
      diagnosis of tuberculosis (TB) has been extensively investigated, its cytokine
      response during natural Mtb infection in humans is largely unknown. In this
      study, LAM-specific IFN-gamma, TNF-alpha, and IL-10 levels following whole blood
      assay were measured in untreated pulmonary TB patients, their contacts and
      community controls at baseline. In treated patients and contacts, cytokines were
      also measured at 6 and 12 months. At entry, 52.8% and 74.8% of controls and
      contacts were QFT-GIT positive, respectively. At baseline, untreated TB patients
      and contacts had significantly lower IFN-gamma and TNF-alpha response compared to
      community controls (p < 0.0001). Besides, untreated patients had significantly
      higher TNF-alpha and IL-10 response compared to their contacts (p < 0.0001). At 6
      months, contacts and treated TB patients had significantly increased INF-gamma
      and TNF-alpha response (p < 0.0001). In TB patients, IFN-gamma increased 10-fold
      following chemotherapy suggesting its potential role for treatment monitoring.
      The data suggests that LAM might have an anti-inflammatory effect during clinical
      TB and early Mtb infection. The data also suggests that LAM-induced IFN-gamma and
      TNF-alpha could be used as biomarkers of protective immunity. 

PMID- 26200932
TI  - Cardiac extracellular matrix proteomics: Challenges, techniques, and clinical
      implications.
AB  - Extracellular matrix (ECM) has emerged as a dynamic tissue component, providing
      not only structural support, but also functionally participating in a wide range
      of signaling events during development, injury, and disease remodeling.
      Investigation of dynamic changes in cardiac ECM proteome is challenging due to
      the relative insolubility of ECM proteins, which results from their
      macromolecular nature, extensive post-translational modification (PTM), and
      tendency to form protein complexes. Finally, the relative abundance of cellular
      and mitochondrial proteins in cardiac tissue further complicates cardiac ECM
      proteomic approaches. Recent developments of various techniques to enrich and
      analyze ECM proteins are playing a major role in overcoming these challenges.
      Application of cardiac ECM proteomics in disease tissues can further provide
      spatial and temporal information relevant to disease diagnosis, prognosis,
      treatment, and engineering of therapeutic candidates for cardiac repair and
      regeneration. 

PMID- 26200935
TI  - Resveratrol as a novel treatment for diseases with mTOR pathway hyperactivation.
AB  - The mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway is
      hyperactivated in a variety of cancers and tumor syndromes. Therefore, mTORC1
      inhibitors are being actively investigated for treatment of neoplasms. The
      concern with the monotherapy use of mTORC1 inhibitors, such as rapamycin, is that
      they cause upregulation of autophagy, a cell survival mechanism, and suppress the
      negative feedback loop to the oncogene Akt. In turn, Akt promotes cell survival,
      causing the therapy to be partially effective, but relapse occurs upon cessation
      of treatment. In this review, we describe the current literature on resveratrol
      as well as our work, which uses rapamycin in combination with resveratrol. We
      found that this combination treatment efficiently blocked upregulation of
      autophagy and restored inhibition of Akt in different cancer and tumor models.
      Interestingly, the combination of rapamycin and resveratrol selectively promoted
      apoptosis of cells with mTOR pathway hyperactivation. Moreover, this combination
      prevented tumor growth and lung metastasis when tested in mouse models. Finally,
      mass spectrometry-based identification of cellular targets of resveratrol
      provided mechanistic insight into the mode of action of resveratrol. The addition
      of resveratrol to rapamycin treatment may be a promising option for selective and
      targeted therapy for diseases with mTORC1 hyperactivation. 

PMID- 26200936
TI  - Applications of Fluorine in Medicinal Chemistry.
AB  - The role of fluorine in drug design and development is expanding rapidly as we
      learn more about the unique properties associated with this unusual element and
      how to deploy it with greater sophistication. The judicious introduction of
      fluorine into a molecule can productively influence conformation, pKa, intrinsic
      potency, membrane permeability, metabolic pathways, and pharmacokinetic
      properties. In addition, (18)F has been established as a useful positron emitting
      isotope for use with in vivo imaging technology that potentially has extensive
      application in drug discovery and development, often limited only by convenient
      synthetic accessibility to labeled compounds. The wide ranging applications of
      fluorine in drug design are providing a strong stimulus for the development of
      new synthetic methodologies that allow more facile access to a wide range of
      fluorinated compounds. In this review, we provide an update on the effects of the
      strategic incorporation of fluorine in drug molecules and applications in
      positron emission tomography. 

PMID- 26200937
TI  - Study of tert-Amyl Methyl Ether Low Temperature Oxidation Using Synchrotron
      Photoionization Mass Spectrometry.
AB  - This paper examines the oxidation reaction of tert-amyl methyl ether (TAME), an
      oxygenated fuel additive, with chlorine radical initiators in the presence of
      oxygen. Data are collected at 298, 550, and 700 K. Reaction intermediates and
      products are probed by a multiplexed chemical kinetics synchrotron
      photoionization mass spectrometer (SPIMS) and characterized on the basis of the
      mass-to-charge ratio, ionization energy, and photoionization spectra. Branching
      fractions of primary products are obtained at the different reaction
      temperatures. CBS-QB3 computations are also carried out to study the potential
      energy surface of the investigated reactions to validate detected primary
      products. 

PMID- 26200938
TI  - Optimization of ion-pair formation between glycopyrronium bromide and different
      ion-pair agents using ACE.
AB  - Glycopyrronium bromide (GLB) is an anticholinergic drug. Its highly polar
      quaternary ammonium group could limit the skin permeation of the topical
      hydrophilic drug. The ion pair formation with suitable anionic molecules was
      suggested to play a role in enhancing the cationic drug transport to the target
      site. The interactions between GLB and different ion-pair agents (IPAs) were
      investigated using ACE. The changes in the effective mobility of 0.05 mM GLB were
      correlated with the increasing concentrations of IPAs in 20 mM BGE of pH 6.2, and
      successfully fitted into a nonlinear binding isotherm equation assuming 1:1
      stoichiometric interaction. The formation constants (Kf ) were 74.33, 28.5,
      18.17, 8.2, 7.6, 5.69, 4.76, and 3.96 M-1 for sodium salts of dodecyl sulfate,
      taurodeoxycholate, taurocholate, glycodeoxycholate, glycocholate, salicylate,
      quinolone sulfonate, and p-toluene sulfonate; respectively. Surfactant's and bile
      salts' concentrations were below CMCs. The partition coefficient of GLB between
      buffer phase and n-octanol was determined successfully in the absence and
      presence of different IPAs. The study confirmed the linear correlation (R2 =
      0.907) between the affinity strength of ion pair and the partition behavior of
      GLB in the presence of anionic molecules at 1:1 molar ratio.

PMID- 26200939
TI  - First Dutch Consensus of Pain Quality Indicators for Pain Treatment Facilities.
AB  - BACKGROUND: There is a general consensus about the need to define and improve the
      quality of pain treatment facilities. Although guidelines and recommendations to
      improve the quality of pain practice management have been launched, provision of
      appropriate pain treatment is inconsistent and the quality of facilities varies
      widely. The aim of the study was to develop an expert-agreed list of quality
      indicators applicable to pain treatment facilities. The list was also intended to
      be used as the basis for a set of criteria for registered status of pain
      treatment facilities. METHODS: The University Pain Center Maastricht at the
      Department of Anesthesiology and Pain Management of the Maastricht University
      Medical Center conducted a 3-round Delphi study in collaboration with the Board
      of the Pain Section of the Dutch Society of Anesthesiologists (NVA). RESULTS:
      Twenty-five quality indicators were selected as relevant to 2 types of pain
      treatment facilities, pain clinics and pain centers. The final expert-agreed list
      consisted of 22 quality indicators covering 7 quality domains: supervision,
      availability of care, staffing level and patient load, quality policy,
      multidisciplinarity, regionalization, and research and education. CONCLUSIONS:
      This set of quality indicators may facilitate organizational evaluation and
      improve insight into service quality from the perspectives of patients, pain
      specialists, and other healthcare professionals. Recommendations for improvements
      to the current set of quality indicators are made. In 2014 the process of
      registering pain treatment facilities in the Netherlands started; facilities can
      register as a pain clinic or pain center.

PMID- 26200941
TI  - Auricular reconstruction using biofabrication-based tissue engineering
      strategies.
AB  - Auricular malformations, which impose a significant social and psychological
      burden, are currently treated using ear prostheses, synthetic implants or
      autologous implants derived from rib cartilage. Advances in the field of
      regenerative medicine and biofabrication provide the possibility to engineer
      functional cartilage with intricate architectures and complex shapes using
      patient-derived or donor cells. However, the development of a successful
      auricular cartilage implant still faces a number of challenges. These challenges
      include the generation of a functional biochemical matrix, the fabrication of a
      customized anatomical shape, and maintenance of that shape. Biofabrication
      technologies may have the potential to overcome these challenges due to their
      ability to reproducibly deposit multiple materials in complex geometries in a
      highly controllable manner. This topical review summarizes this potential of
      biofabrication technologies for the generation of implants for auricular
      reconstruction. In particular, it aims to discuss how biofabrication
      technologies, although still in pre-clinical phase, could overcome the challenges
      of generating and maintaining the desired auricular shapes. Finally, remaining
      bottlenecks and future directions are discussed. 

PMID- 26200940
TI  - An anatomical study of porcine peripheral nerve and its potential use in nerve
      tissue engineering.
AB  - Current nerve tissue engineering applications are adopting xenogeneic nerve
      tissue as potential nerve grafts to help aid nerve regeneration. However, there
      is little literature that describes the exact location, anatomy and physiology of
      these nerves to highlight their potential as a donor graft. The aim of this study
      was to identify and characterise the structural and extracellular matrix (ECM)
      components of porcine peripheral nerves in the hind leg. Methods included the
      dissection of porcine nerves, localisation, characterisation and quantification
      of the ECM components and identification of nerve cells. Results showed a
      noticeable variance between porcine and rat nerve (a commonly studied species) in
      terms of fascicle number. The study also revealed that when porcine peripheral
      nerves branch, a decrease in fascicle number and size was evident. Porcine ECM
      and nerve fascicles were found to be predominately comprised of collagen together
      with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve
      growth factor receptor p75 also revealed the localisation of Schwann cells around
      and inside the fascicles. In conclusion, it is shown that porcine peripheral
      nerves possess a microstructure similar to that found in rat, and is not
      dissimilar to human. This finding could extend to the suggestion that due to the
      similarities in anatomy to human nerve, porcine nerves may have utility as a
      nerve graft providing guidance and support to regenerating axons. 

PMID- 26200942
TI  - Acquired haemophilia and the New Oral Anticoagulants (NOACs): coincidence or drug
      induced adverse event?

PMID- 26200943
TI  - Hypoxia inhibits nephrogenesis through paracrine Vegfa despite the ability to
      enhance tubulogenesis.
AB  - Reduced nephron number predisposes to hypertension and kidney disease.
      Interaction of the branching ureteric bud and surrounding mesenchymal cells
      determines nephron number. Since oxygen supply may be critical for intrauterine
      development, we tested whether hypoxia and hypoxia-inducible factor-1alpha (HIF
      1alpha) influence nephrogenesis. We found that HIF-1alpha is required for
      branching of MDCK cells. In addition, culture of metanephric mouse kidneys with
      ureteric bud cell-specific stabilization or knockout of HIF-1alpha revealed a
      positive impact of HIF-1alpha on nephrogenesis. In contrast, widespread
      stabilization of HIF-1alpha in metanephric kidneys through hypoxia or HIF
      stabilizers impaired nephrogenesis, and pharmacological HIF inhibition enhanced
      nephrogenesis. Several lines of evidence suggest an inhibitory effect through the
      hypoxia response of mesenchymal cells. HIF-1alpha was expressed in mesenchymal
      cells during nephrogenesis. Expression of the anti-branching factors Bmp4 and
      Vegfa, secreted by mesenchymal cells, was increased upon HIF stabilization. The
      conditioned medium from hypoxic metanephric kidneys inhibited MDCK branching,
      which was partially rescued by Vegfa antibodies. Thus, the effect of HIF-1alpha
      on nephrogenesis appears context dependent. While HIF-1alpha in the ureteric bud
      is of importance for proper branching morphogenesis, the net effect of hypoxia
      induced HIF activation in the embryonic kidney appears to be mesenchymal cell
      dependent inhibition of ureter branching.

PMID- 26200944
TI  - Smoking increases the risk of all-cause and cardiovascular mortality in patients
      with chronic kidney disease.
AB  - Little is known about the magnitude and nature of the combined effect of chronic
      kidney disease (CKD) and smoking on cardiovascular diseases. We studied this in a
      Japanese population using a pooled analysis of 15,468 men and 19,154 women aged
      40-89 years enrolled in 8 cohort studies. The risk of mortality from all-causes
      and cardiovascular disease was compared in 6 gender-specific categories of
      baseline CKD status (non-CKD or CKD) and smoking habits (lifelong never smoked,
      former smokers, or currently smoking). CKD was defined as a decreased level of
      estimated glomerular filtration rate (under 60 ml/min per 1.73 m(2)) and/or
      dipstick proteinuria. Hazard ratios were estimated for each category, relative to
      never smokers without CKD. During the follow-up period (mean 14.8 years), there
      were 6771 deaths, 1975 of which were due to cardiovascular diseases. In both men
      and women, current or former smokers with CKD had the first or second highest
      crude mortality rates from all-cause and cardiovascular diseases among the 6
      categories. After adjustment for age and other major cardiovascular risk factors,
      the hazard ratios in male and female current smokers with CKD were 2.26 (95%
      confidence interval, 1.95-2.63) and 1.78 (1.36-2.32) for all-causes, and 2.66
      (2.04-3.47) and 1.71 (1.10-2.67) for cardiovascular diseases, respectively. Thus,
      coexistence of CKD and smoking may markedly increase the risk of all-cause and
      cardiovascular mortality. 

PMID- 26200946
TI  - Biomarkers of rapid chronic kidney disease progression in type 2 diabetes.
AB  - Here we evaluated the performance of a large set of serum biomarkers for the
      prediction of rapid progression of chronic kidney disease (CKD) in patients with
      type 2 diabetes. We used a case-control design nested within a prospective cohort
      of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year
      period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153
      controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers
      were measured and logistic regression was used with forward selection to choose a
      subset that were maximized on top of clinical variables including age, gender,
      hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the
      best number of biomarkers to retain and evaluate for predictive performance.
      Ultimately, 30 biomarkers showed significant associations with rapid progression
      and adjusted for clinical characteristics. A panel of 14 biomarkers increased the
      area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers
      selected included fibroblast growth factor-21, the symmetric to asymmetric
      dimethylarginine ratio, beta2-microglobulin, C16-acylcarnitine, and kidney injury
      molecule-1. Use of more extensive clinical data including prebaseline eGFR slope
      improved prediction but to a lesser extent than biomarkers (area under the ROC
      curve of 0.793). Thus we identified several novel associations of biomarkers with
      CKD progression and the utility of a small panel of biomarkers to improve
      prediction.

PMID- 26200947
TI  - Th-17 cell activation in response to high salt following acute kidney injury is
      associated with progressive fibrosis and attenuated by AT-1R antagonism.
AB  - Exposure of rats to elevated dietary salt following recovery from acute kidney
      injury (AKI) accelerates the transition to chronic kidney disease (CKD), and is
      dependent on lymphocyte activity. Here we tested whether high salt diet triggers
      lymphocyte activation in postischemic kidneys to worsen renal inflammation and
      fibrosis. Male Sprague-Dawley rats on a 0.4% salt diet were subjected to left
      unilateral ischemia-reperfusion and allowed to recover for 5 weeks. This resulted
      in a mild elevation of CD4(+) T cells relative to sham animals. Contralateral
      unilateral nephrectomy and elevated dietary salt (4%) for 4 extra weeks hastened
      CKD and interstitial fibrosis. Activated T cells were increased in the kidney
      threefold after 4 weeks of elevated dietary salt exposure relative to post-AKI
      rats before salt feeding. The T cell subset was largely positive for IL-17,
      indicative of Th-17 cells. Because angiotensin II activity may influence
      lymphocyte activation, injured rats were given the AT1R antagonist, losartan,
      along with high salt diet. This significantly reduced the number of renal Th-17
      cells to levels of sham rats, and significantly reduced the salt-induced increase
      in fibrosis to about half. In vitro studies in AKI-primed CD4(+) T cells
      indicated that angiotensin II and extracellular sodium enhanced, and losartan
      inhibited, IL-17 expression. Thus, dietary salt modulates immune cell activity in
      postischemic recovering kidneys because of the activity of local RAS, suggesting
      the participation of these cells in CKD progression post-AKI.

PMID- 26200948
TI  - Mimicking postmenopausal steroid metabolism in breast cancer cell culture:
      Differences in response to DHEA or other steroids as hormone sources.
AB  - Following menopause virtually 100% of estrogens are synthesized in peripheral
      target tissues from precursor steroids of adrenal origin. These steroids are the
      unique source of sex steroids in these women. This positions some steroid
      metabolizing enzymes as primary targets for novel therapies for estrogen receptor
      positive (ER+) breast cancer. However, previous research on the steroid
      converting enzymes has been performed using their direct substrate as a hormone
      source, depending on the facility where studied and the robust signal obtained.
      These experiments may not always provide an accurate reflection of physiological
      and post-menopausal conditions. We suggest providing dehydroepiandrosterone
      (DHEA) as an intracrinological hormone source, and comparing the role of steroid
      converting enzymes using DHEA and their direct substrates when an extensive
      mechanistic understanding is required. Here, we present a comparative study of
      these enzymes with the provision of DHEA and the direct substrates, estrone (E1)
      or dihydrotestosterone (DHT), or additional steroids as hormone sources, in
      breast cancer cells. Enzyme knockdown by respective specific siRNAs and
      observations on the resulting differences in biological function were carried
      out. Cell biology studies showed no difference in biological function for 17beta
      HSD1 and 17beta-HSD7 when cultured with different steroid hormones: cell
      proliferation and estradiol levels decreased, whereas DHT accumulated; cyclinD1,
      PCNA, and pS2 were down-regulated after knocking down these two enzymes, although
      the quantitative results varied. However, culture medium supplementation was
      found to have a marked impact on the study of 3alpha-HSD3. We demonstrated that
      provision of different steroids as a substrate or hormone sources may promote
      modified biological effects: provision of DHEA is the preferred choice to mimic
      postmenopausal steroid metabolism in cell culture.

PMID- 26200945
TI  - A polycystin-centric view of cyst formation and disease: the polycystins
      revisited.
AB  - It is 20 years since the identification of PKD1, the major gene mutated in
      autosomal dominant polycystic kidney disease (ADPKD), followed closely by the
      cloning of PKD2. These major breakthroughs have led in turn to a period of
      intense investigation into the function of the two proteins encoded, polycystin-1
      and polycystin-2, and how defects in either protein lead to cyst formation and
      nonrenal phenotypes. In this review, we summarize the major findings in this area
      and present a current model of how the polycystin proteins function in health and
      disease.

PMID- 26200949
TI  - Therapeutic actions of translocator protein (18 kDa) ligands in experimental
      models of psychiatric disorders and neurodegenerative diseases.
AB  - Translocator protein (TSPO) is an 18kDa protein located at contact sites between
      the outer and the inner mitochondrial membrane. Numerous studies have associated
      TSPO with the translocation of cholesterol across the aqueous mitochondrial
      intermembrane space and the regulation of steroidogenesis, as well as with the
      control of some other mitochondrial functions, such as mitochondrial respiration,
      mitochondrial permeability transition pore opening, apoptosis and cell
      proliferation. In the brain, changes in TSPO expression occur in several
      neuropathological conditions including neurodegenerative diseases and psychiatric
      disorders. Furthermore, TSPO ligands have been shown to promote neuroprotection
      in animal models of brain pathology. At least in some cases, the mechanisms of
      neuroprotection are associated with modifications in brain steroidogenesis. In
      addition, regulation of neuroinflammation seems to be a common mechanism in the
      neuroprotective actions of TSPO ligands in different animal models of brain
      pathology. 

PMID- 26200950
TI  - The Antipsychotic Effects of Omega-3 Fatty Acids in Rats.
AB  - BACKGROUND: In humans, omega-3 fatty acids are necessary for cell membranes,
      brain function and nerve transmission continuation. When animals are exposed to a
      new environment-or as a result of an apomorphine application that creates an
      agonistic effect on D1 and D2 receptors-they display behavioral reactions like
      rearing and stereotypy. This study aims to reveal the possible antipsychotic and
      oxidative effects of omega-3 fatty acids by comparing with chlorpromazine, a
      conventional antipsychotic drug, through evaluating the novelty-induced rearing
      and apomorphine-induced stereotypic behaviors, as well as malondialdehyde and
      glutathione levels in rats. METHODS: Twenty-eight, adult, male, Wistar rats were
      used in the study. Briefly, 4 groups of rats (n = 7) were administered
      docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) (300 mg/kg; DHA: 120
      mg/kg + EPA: 180 mg/kg intraperitoneally [IP]), DHA + EPA (150 mg/kg; DHA: 60
      mg/kg + EPA: 90 mg/kg IP), chlorpromazine (1 mg/kg, IP) and isotonic saline (1
      mL/kg, IP). One hour later, apomorphine (2 mg/kg, subcutaneously) was
      administered to each rat. After the apomorphine administration, rats were
      observed for stereotypic behavior. RESULTS: This study shows that omega-3 fatty
      acids, "similar to antipsychotics," reversed the psychotic like effects, increase
      of oxidants and decrease of antioxidants that are composed experimentally in
      rats. CONCLUSIONS: The application of omega-3 fatty acids has antipsychotic
      effects and causes an oxidative imbalance. This study adds new evidence to the
      current literature regarding the possible antipsychotic effects of omega-3 fatty
      acids.

PMID- 26200951
TI  - Pomalidomide-Induced Pulmonary Toxicity in Multiple Myeloma.

PMID- 26200952
TI  - Do major histocompatibility complex tag single nucleotide polymorphisms
      accurately identify HLA-B27 in the Turkish population?
AB  - OBJECTIVE: To evaluate the performance of human leukocyte antigen (HLA)-B27 tag
      single nucleotide polymorphisms (SNPs) by polymerase chain reaction - restriction
      fragment length polymorphism (PCR-RFLP). METHODS: We genotyped three SNPs
      (rs116488202, rs13202464 and rs4349859). The primers were designed using Primer3
      algorithm via primer-BLAST interface. PCR products were digested by using NlaIII,
      BmrI and TaqalphaI enzymes. Quality control was performed by DNA sequence
      analysis. RESULTS: In total, 207 patients with ankylosing spondylitis and 32
      healthy controls were included in the study. The sensitivity and specificity of
      SNPs rs116488202 and rs4349859 in identifying HLA-B27 were identical and adequate
      at 0.946 and 1.000, respectively. On the other hand, the sensitivity and
      specificity for rs13202464 was 0.878 and 0.934, respectively. The presence of
      another SNP (rs141774149) in close proximity to rs116488202 complicated the
      analysis for RFLP and required that we sequence all the T allele carrying
      samples. CONCLUSION: The SNPs rs116488202 and rs4349859 may have a place in the
      identification of HLA-B27 in the Turkish population; however, methods other than
      PCR-RFLP should be considered.

PMID- 26200953
TI  - Mangiferin Protects Retinal Ganglion Cells in Ischemic Mouse Retina via SIRT1.
AB  - PURPOSE: To investigate whether mangiferin can increase the viability of retinal
      ganglion cells (RGCs) in ischemic mouse retina, and to determine the possible
      mechanism of neuroprotection. METHODS: C57BL/6J mice underwent constant elevation
      of intraocular pressure for 60 min and received saline or mangiferin (30 mg/kg)
      intraperitoneally once daily until sacrifice. HIF-1alpha, GFAP and SIRT1
      expression was assessed at 1, 4, and 7 days after retinal ischemia. Bax and Bcl-2
      expression was also analyzed at 1 and 4 days. RGC survival was assessed by
      labeling flat-mounted retinas with Brn3a at 2 weeks after retinal ischemia. The
      effect of co-treatment with mangiferin and sirtinol (SIRT1 inhibitor) was also
      evaluated. RESULTS: The expression of HIF-1alpha and GFAP was upregulated in
      saline-treated retinas within 7 days after ischemia. Mangiferin treatment
      suppressed this upregulation. The expression of SIRT1 was downregulated in saline
      treated ischemic retinas. This downregulation was reversed by mangiferin
      treatment, resulting in a significant difference from saline-treated ischemic
      retinas. In mangiferin-treated ischemic retinas, Bax expression was
      downregulated, whereas Bcl-2 expression was upregulated in comparison with saline
      treated ischemic retinas. Mangiferin treatment protected ischemic retinas against
      RGC loss. Treatment of sirtinol decreased the neuroprotective effect of
      mangiferin. CONCLUSIONS: Our findings suggest that mangiferin has a
      neuroprotective effect on RGC through downregulation of HIF-1a and GFAP, and
      upregulation of SIRT1 in ischemic mouse retinas. We suggest that mangiferin might
      be a potential neuroprotective agent against RGC loss under oxidative stress.

PMID- 26200954
TI  - Egg drop syndrome virus enters duck embryonic fibroblast cells via clathrin
      mediated endocytosis.
AB  - Previous studies of egg drop syndrome virus (EDSV) is restricted to serological
      surveys, disease diagnostics, and complete viral genome analysis. Consequently,
      the infection characteristics and entry routes of EDSV are poorly understood.
      Therefore, we aimed to explore the entry pathway of EDSV into duck embryonic
      fibroblast (DEF) cells as well as the infection characteristics and proliferation
      of EDSV in primary DEF and primary chicken embryo liver (CEL) cells. Transmission
      electron microscopy revealed that the virus triggered DEF cell membrane
      invagination as early as 10 min post-infection and that integrated endocytic
      vesicles formed at 20 min post-infection. The virus yield in EDSV-infected DEF
      cells treated with chlorpromazine (CPZ), sucrose, methyl-beta-cyclodextrin
      (MbetaCD), or NH4Cl was measured by quantitative real-time PCR. Compared with the
      mock treatment, CPZ and sucrose greatly inhibited the production of viral progeny
      in a dose-dependent manner, while MbetaCD treatment did not result in a
      significant difference. Furthermore, NH4Cl had a strong inhibitory effect on the
      production of EDSV progeny. In addition, indirect immunofluorescence demonstrated
      that virus particles clustered on the surface of DEF cells treated with CPZ or
      sucrose. These results indicate that EDSV enters DEF cells through clathrin
      mediated endocytosis followed by a pH-dependent step, which is similar to the
      mechanism of entry of human adenovirus types 2 and 5.

PMID- 26200955
TI  - Nonstructural protein Pns12 of rice dwarf virus is a principal regulator for
      viral replication and infection in its insect vector.
AB  - Plant reoviruses are thought to replicate and assemble within cytoplasmic
      structures called viroplasms. The molecular mechanisms underling the formation of
      the viroplasm during infection of rice dwarf virus (RDV), a plant reovirus, in
      its leafhopper vector cells remain poorly understood. Viral nonstructural protein
      Pns12 forms viroplasm-like inclusions in the absence of viral infection,
      suggesting that the viroplasm matrix is basically composed of Pns12. Here, we
      demonstrated that core capsid protein P3 and nonstructural protein Pns11 were
      recruited in the viroplasm by direct interaction with Pns12, whereas
      nonstructural protein Pns6 was recruited through interaction with Pns11. The
      introduction of dsRNA from Pns12 gene into cultured insect vector cells or intact
      insect strongly inhibited such viroplasm formation, preventing efficient viral
      spread in the leafhopper in vitro and in vivo. Thus, nonstructural protein Pns12
      of RDV is a principal regulator for viral replication and infection in its insect
      vector. 

PMID- 26200956
TI  - FREQUENCY OF Candida SPECIES IN A TERTIARY CARE HOSPITAL IN TRIANGULO MINEIRO,
      MINAS GERAIS STATE, BRAZIL.
AB  - Infections by Candida species are a high-impact problem in public health due to
      their wide incidence in hospitalized patients. The goal of this study was to
      evaluate frequency, susceptibility to antifungals, and genetic polymorphism of
      Candida species isolated from clinical specimens of hospitalized patients. The
      Candida isolates included in this study were obtained from blood cultures,
      abdominal fluids, and central venous catheters (CVC) of hospitalized patients at
      the Clinical Hospital of the Federal University of Uberlandia during the period
      of July 2010 - June 2011. Susceptibility tests were conducted by the broth
      microdilution method. The RAPD-PCR tests used employed initiator oligonucleotides
      OPA09, OPB11, and OPE06. Of the 63 Candida isolates, 18 (28.5%) were C. albicans,
      20 (31.7%) were C. parapsilosis complex species, 14 (22.2%) C. tropicalis, four
      (6.4%) C. glabrata, four (6.4%) C. krusei, two (3.3%) C. kefyr, and one (1.6%) C.
      lusitaniae. In vitro resistance to amphotericin B was observed in 12.7% of
      isolates. In vitro resistance to azoles was not detected, except for C. krusei.
      The two primers, OPA09 and OPB11, were able to distinguish different species.
      Isolates of C. albicans and C. parapsilosis complex species presented six and
      five clusters, respectively, with the OPA09 marker by RAPD-PCR, showing the
      genetic variability of the isolates of those species. It was concluded that
      members of the C. parapsilosis complex were the most frequent species found, and
      most isolates were susceptible to the antifungals amphotericin B, flucozanole,
      and itraconazole. High genetic polymorphisms were observed for isolates of C.
      albicans and C. parapsilosis complex species, mainly with the OPA09 marker. 

PMID- 26200957
TI  - RAW TROPICAL OYSTERS AS VEHICLES FOR MULTIDRUG-RESISTANT Vibrio parahaemolyticus.
AB  - The following study aimed to determine the antimicrobial susceptibility profile
      of Vibrio parahaemolyticus strains from fresh and frozen oysters Crassostrea
      rhizophorae sold in Fortaleza-Brazil. An antibiogram was performed on 87 isolates
      using nine antibiotics: gentamicin (Gen 10 ug), ampicillin (Amp 10 ug),
      penicillin G (Pen 10U), ciprofloxacin (Cip 5 ug), chloramphenicol (Chl 30 ug),
      nalidixic acid (Nal 30 ug), tetracycline (Tet 30 ug), vancomycin (Van 30 ug) and
      erythromycin (Ery 15 ug). All strains were resistant to at least one antibiotic,
      and 85 (97.7%) were multi-resistant, with predominance of the Van+ Pen+Amp
      resistance profile (n = 46). Plasmid resistance to Pen, Amp and Ery was detected.
      Thus, the risk that raw oyster consumption poses to the health of consumers is
      highlighted, due to the fact that these bivalves may host antibacterial-resistant
      microorganisms.

PMID- 26200958
TI  - ANTHELMINTIC ACTIVITY OF LAPACHOL, beta-LAPACHONE AND ITS DERIVATIVES AGAINST
      Toxocara canis LARVAE.
AB  - Anthelmintics used for intestinal helminthiasis treatment are generally
      effective; however, their effectiveness in tissue parasitosis (i.e. visceral
      toxocariasis) is moderate. The aim of this study was to evaluate the in vitro
      activity of lapachol, beta-lapachone and phenazines in relation to the viability
      of Toxocara canis larvae. A concentration of 2 mg/mL (in duplicate) of the
      compounds was tested using microculture plates containing Toxocara canis larvae
      in an RPMI-1640 environment, incubated at 37  degrees C in 5% CO2 tension for 48
      hours. In the 2 mg/mL concentration, four phenazines, lapachol and three of its
      derivatives presented a larvicide/larvistatic activity of 100%. Then, the minimum
      larvicide/larvistatic concentration (MLC) test was conducted. The compounds that
      presented the best results were nor-lapachol (MLC, 1 mg/mL), lapachol (MLC 0.5
      mg/mL), beta-lapachone, and beta-C-allyl-lawsone (MLC, 0.25 mg/mL). The larvae
      exposed to the compounds, at best MLC with 100% in vitro activity larvicide, were
      inoculated into healthy BALB/c mice and were not capable of causing infection,
      confirming the larvicide potential in vitro of these compounds. 

PMID- 26200959
TI  - MOLECULAR CHARACTERIZATION AND SEQUENCE PHYLOGENETIC ANALYSIS OF SURFACE ANTIGEN
      3 (SAG3) GENE OF LOCAL INDIAN ISOLATES (CHENNAI AND IZATNAGAR) OF Toxoplasma
      gondii.
AB  - CONTEXT AND OBJECTIVE: The molecular characterization of local isolates of
      Toxoplasma gondii is considered significant so as to assess the homologous
      variations between the different loci of various strains of parasites. DESIGN AND
      SETTING: The present communication deals with the molecular cloning and sequence
      analysis of the 1158 bp entire open reading frame (ORF) of surface antigen 3
      (SAG3) of two Indian T. gondii isolates (Chennai and Izatnagar) being maintained
      as cryostock at the IVRI. METHOD: The surface antigen 3 (SAG3) of two local
      Indian isolates were cloned and sequenced before being compared with the
      available published sequences. RESULTS: The sequence comparison analysis revealed
      99.9% homology with the standard published RH strain sequence of T. gondii. The
      strains were also compared with other established published sequences and found
      to be most related to the P-Br strain and CEP strain (both 99.3%), and least with
      PRU strain (98.4%). However, the two Indian isolates had 100% homology between
      them. CONCLUSION: Finally, it was concluded that the Indian isolates were closer
      to the RH strain than to the P-Br strain (Brazilian strain), the CEP strain and
      the PRU strains (USA), with respect to nucleotide homology. The two Indian
      isolates used in the present study are known to vary between themselves, as far
      as homologies related to other genes are concerned, but they were found to be
      100% homologous as far as SAG3 locus is concerned. This could be attributed to
      the fact that this SAG3 might be a conserved locus and thereby, further detailed
      studies are thereby warranted to exploit the use of this particular molecule in
      diagnostics and immunoprophylactics. The findings are important from the point of
      view of molecular phylogeny.

PMID- 26200960
TI  - OCCURRENCE OF Blastocystis spp. IN UBERABA, MINAS GERAIS, BRAZIL.
AB  - Intestinal parasites are a problem for public health all over the world. The
      infection with Blastocystis, a protozoan of controversial pathogenicity, is one
      of the most common among them all. In this study, the occurrence of intestinal
      parasites, with emphasis on Blastocystis, in patients at the Universidade Federal
      do Triangulo Mineiro was investigated in Uberaba (MG) through microscopy of
      direct smears and fecal concentrates using Ritchie's method. Feces of 1,323
      patients were examined from April 2011 to May 2012. In 28.7% of them at least one
      intestinal parasite was identified, and the most frequent organisms were
      Blastocystis spp. (17.8%) and Giardia intestinalis (7.4%). The occurrence of
      parasitism was higher in children aged 6 -10 years old, and the infection with
      Blastocystis spp. was higher above the age of six (p < 0.001). The exclusive
      presence of G. intestinalis and of Blastocystis spp. was observed in 5.4% and
      12.2% of the patients, respectively. Regarding patients with diarrheic feces, 8%
      revealed unique parasitism of Blastocystis spp. Other intestinal parasites
      observed in children were Ascaris lumbricoides (0.3%) and Entamoeba
      histolytica/dispar/moshkovskii (1.4%). The Ritchie's method was more sensitive
      (92.8%) when compared to direct microscopy (89.8%), with high agreement between
      them (97.7%, kappa = 0.92). In conclusion, the occurrence of Blastocystis spp. in
      Uberaba is high and the presence of diarrheic feces with exclusive presence of
      the parasite of Blastocystis spp. was observed.

PMID- 26200961
TI  - SAINT LOUIS ENCEPHALITIS VIRUS IN MATO GROSSO, CENTRAL-WESTERN BRAZIL.
AB  - The dengue virus (DENV), which is frequently involved in large epidemics, and the
      yellow fever virus (YFV), which is responsible for sporadic sylvatic outbreaks,
      are considered the most important flaviviruses circulating in Brazil. Because of
      that, laboratorial diagnosis of acute undifferentiated febrile illness during
      epidemic periods is frequently directed towards these viruses, which may
      eventually hinder the detection of other circulating flaviviruses, including the
      Saint Louis encephalitis virus (SLEV), which is widely dispersed across the
      Americas. The aim of this study was to conduct a molecular investigation of 11
      flaviviruses using 604 serum samples obtained from patients during a large dengue
      fever outbreak in the state of Mato Grosso (MT) between 2011 and 2012.
      Simultaneously, 3,433 female Culex spp. collected with Nasci aspirators in the
      city of Cuiaba, MT, in 2013, and allocated to 409 pools containing 1-10
      mosquitoes, were also tested by multiplex semi-nested reverse transcription PCR
      for the same flaviviruses. SLEV was detected in three patients co-infected with
      DENV-4 from the cities of Cuiaba and Varzea Grande. One of them was a triple co
      infection with DENV-1. None of them mentioned recent travel or access to
      sylvatic/rural regions, indicating that transmission might have occurred within
      the metropolitan area. Regarding mosquito samples, one pool containing one Culex
      quinquefasciatus female was positive for SLEV, with a minimum infection rate
      (MIR) of 0.29 per 1000 specimens of this species. Phylogenetic analysis indicates
      both human and mosquito SLEV cluster, with isolates from genotype V-A obtained
      from animals in the Amazon region, in the state of Para. This is the first report
      of SLEV molecular identification in MT.

PMID- 26200962
TI  - LACK OF ASSOCIATION BETWEEN HERPESVIRUS DETECTION IN SALIVA AND GINGIVITIS IN HIV
      INFECTED CHILDREN.
AB  - The aims of this study were to compare the detection of human herpesviruses
      (HHVs) in the saliva of HIV-infected and healthy control children, and to
      evaluate associations between viral infection and gingivitis and
      immunodeficiency. Saliva samples were collected from 48 HIV-infected and 48
      healthy control children. Clinical and laboratory data were collected during
      dental visits and from medical records. A trained dentist determined gingival
      indices and extension of gingivitis. Saliva samples were tested for herpes
      simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV),
      Epstein-Barr virus (EBV), and cytomegalovirus (CMV) by nested polymerase chain
      reaction assays. Thirty-five HIV-infected and 16 control children had gingivitis.
      Seventeen (35.4%) HIV-infected children and 13 (27%) control children were
      positive for HHVs. CMV was the most commonly detected HHV in both groups (HIV
      infected, 25%; control, 12.5%), followed by HSV-1 (6.2% in both groups) and HSV-2
      (HIV-infected, 4.2%; control, 8.3%). The presence of HHVs in saliva was not
      associated with the presence of gingivitis in HIV-1-infected children (p = 0.104)
      or healthy control children (p = 0.251), or with immunosuppression in HIV
      infected individuals (p = 0.447). Gingivitis was correlated with HIV infection (p
      = 0.0001). These results suggest that asymptomatic salivary detection of HHVs is
      common in HIV-infected and healthy children, and that it is not associated with
      gingivitis. 

PMID- 26200963
TI  - INVENTORY OF MOSQUITOES (DIPTERA: CULICIDAE) IN CONSERVATION UNITS IN BRAZILIAN
      TROPICAL DRY FORESTS.
AB  - In Brazil, most studies of the Culicidae family are concentrated in rainforest
      regions. As such, there is a lack of knowledge regarding the diversity of
      Culicidae in regions with different climatic and vegetational characteristics.
      The aim of this study was to compile an inventory of Culicidae in protected areas
      of the semi-arid region of the state of Minas Gerais, Brazil, in order to better
      understand the diversity of the family within this region. The study was
      conducted across four protected areas in the northern region of the state, in
      tropical dry forest (TDF) fragments. Sampling methods included Shannon trap and
      CDC light trap, as well as active collection. A total of 11,219 mosquito
      specimens were collected between August 2008 and July 2012, belonging to 11
      genera and 45 species; 15 new records for the state of Minas Gerais were
      registered, as well as 26 new records for semi-arid regions within the state. The
      high number of new Culicidae records in this region demonstrates the importance
      of inventory studies for increasing the knowledge of culicid biodiversity in
      Minas Gerais, and in particular within semi-arid regions of the state.

PMID- 26200964
TI  - PHLEBOTOMINE FAUNA (DIPTERA: PSYCHODIDAE) IN AN AREA OF FISHING TOURISM IN
      CENTRAL-WESTERN BRAZIL.
AB  - The aim of this study was to identify behavioral aspects of the sandfly fauna of
      a fishing tourism area in the municipality of Bonito (MS). Monthly captures were
      undertaken from December 2009 to November 2010, using automatic CDC type light
      traps, from 18h00 to 06h00, in a forested area, a savannah area, peridomiciles
      and animal shelters near peridomiciliary areas. Nyssomyia whitmani was the most
      frequent out of a total of 6,699 specimens collected, belonging to 16 species,
      followed by Psathyromyia bigeniculata and Lutzomyia longipalpis, found in all the
      environments investigated, though in their greatest numbers in the animal
      shelters. Ny. whitmani exhibited its highest frequencies during the dry months,
      coincident with the fishing season, when the risk of transmission of cutaneous
      leishmaniasis for tourists and inhabitants increases. Noteworthy was the finding
      of two species naturally infected by flagellates: Ny. whitmani and Pa.
      bigeniculata. The local population and visiting tourists should be warned of the
      threat posed by leishmaniasis and the health authorities alerted to the need for
      adopting environmental sanitary measures, especially regarding such animal
      shelters as they seem to provide favorable conditions to the proliferation,
      maintenance and breeding opportunities of phlebotomines.

PMID- 26200965
TI  - HEAD LICE IN HAIR SAMPLES FROM YOUTHS, ADULTS AND THE ELDERLY IN MANAUS, AMAZONAS
      STATE, BRAZIL.
AB  - A study of head lice infestations among young people, adults and elderly
      individuals was conducted from August 2010 to July 2013 in Manaus, AM, Northern
      Brazil. Hair samples collected from 1,860 individuals in 18 barber shops and
      beauty parlors were examined for the ectoparasite. The occurrence of pediculosis
      and its association with factors, such as sex, age, ethnicity, hair
      characteristics and the socioeconomic profile of salon customers, salon location
      and seasonal variation were determined. The overall occurrence rate was 2.84%.
      Occurrence was higher in hair samples from non-blacks and the elderly. Higher
      occurrence was also observed during kindergarten, elementary and junior education
      school holidays. The results indicate that the occurrence of head lice among
      young people, adults and the elderly in Manaus is relatively low compared to that
      determined in children and in other regions of the country. After children, the
      elderly were the most affected. The study also indicated the need to adopt
      additional procedures to improve surveys among the population with low or no
      purchasing power, which is usually the most affected by this ectoparasitic
      disease. 

PMID- 26200967
TI  - MOLECULAR IDENTIFICATION AND ANTIMICROBIAL RESISTANCE PATTERN OF SEVEN CLINICAL
      ISOLATES OF Nocardia spp. IN BRAZIL.
AB  - Nocardia is a ubiquitous microorganism related to pyogranulomatous infection,
      which is difficult to treat in humans and animals. The occurrence of the disease
      is on the rise in many countries due to an increase in immunosuppressive diseases
      and treatments. This report of cases from Brazil presents the genotypic
      characterization and the antimicrobial susceptibility pattern using the disk
      diffusion method and inhibitory minimal concentration with E-test(r) strips. In
      summary, this report focuses on infections in young adult men, of which three
      cases were cutaneous, two pulmonary, one neurological and one systemic. The
      pulmonary, neurological and systemic cases were attributed to immunosuppressive
      diseases or treatments. Sequencing analysis of the 16S rRNA segments (1491 bp)
      identified four isolates of Nocardia farcinica, two isolates of Nocardia nova and
      one isolate of Nocardia asiatica. N. farcinica was involved in two cutaneous, one
      systemic and other pulmonary cases; N. nova was involved in one neurological and
      one pulmonary case; and Nocardia asiatica in one cutaneous case. The disk
      diffusion antimicrobial susceptibility test showed that the most effective
      antimicrobials were amikacin (100%), amoxicillin/clavulanate (100%), cephalexin
      (100%) and ceftiofur (100%), while isolates had presented most resistance to
      gentamicin (43%), sulfamethoxazole/trimethoprim (43%) and ampicillin (29%).
      However, on the inhibitory minimal concentration test (MIC test), only one of the
      four isolates of Nocardia farcinica was resistant to
      sulfamethoxazole/trimethoprim. 

PMID- 26200966
TI  - EFFECTS OF VITAMIN C SUPPLEMENTATION ON THE CHRONIC PHASE OF CHAGAS DISEASE.
AB  - INTRODUCTION: In order to examine the effectiveness of vitamin C (ascorbic acid)
      in combating the oxidative insult caused by Trypanosoma cruzi during the
      development of the chronic phase of Chagas disease, Swiss mice were infected
      intraperitoneally with 5.0 * 104 trypomastigotes of T. cruzi QM1strain. METHODS:
      Mice were given supplements of two different doses of vitamin C for 180 days.
      Levels of lipid oxidation (as indicated by thiobarbituric acid reactive
      substances-TBARS), total peroxide, vitamin C, and reduced glutathione were
      measured in the plasma, TBARS, total peroxide and vitamin C were measured in the
      myocardium and histopathologic analysis was undertaken in heart, colon and
      skeletal muscle. RESULTS: Animals that received a dose equivalent to 500 mg of
      vitamin C daily showed increased production of ROS in plasma and myocardium and a
      greater degree of inflammation and necrosis in skeletal muscles than those that
      received a lower dose or no vitamin C whatsoever. CONCLUSION: Although some
      research has shown the antioxidant effect of vitamin C, the results showed that
      animals subject to a 500 mg dose of vitamin C showed greater tissue damage in the
      chronic phase of Chagas disease, probably due to the paradoxical actions of the
      substance, which in this pathology, will have acted as a pro-oxidant or pro
      inflammatory.

PMID- 26200968
TI  - GENOTYPE CHARACTERIZATION OF Leishmania (Viannia) braziliensis ISOLATED FROM
      HUMAN AND CANINE BIOPSIES WITH AMERICAN CUTANEOUS LEISHMANIASIS.
AB  - INTRODUCTION: American tegumentary leishmaniasis (ATL) can be caused by
      Leishmania (Viannia) braziliensis complex. The evolution of ATL initially results
      in lesions and can develop into disseminated or diffuse forms. The genetic
      diversity of L. (V.) braziliensis in some endemic areas of Brazil has been poorly
      studied, such as in the state of Sao Paulo. This study analyzed the genetic
      diversity of L. (V.) braziliensis isolates collected from patients and dogs with
      LTA from the state of Sao Paulo. METHODS: Leishmaniasis diagnosis was determined
      by PCR. The 132 biopsies were collected in different regions of Sao Paulo State,
      Brazil (36 municipalities). The genetic characterization of L. (V.) braziliensis
      isolates was tested by RFLP-PCR using DNA extracted from biopsies. The primer set
      amplified a specific region of Leishmania internal transcribed spacers of the
      ribosomal DNA locus. RESULTS: Of the 132 samples, 52 (40%) were completely
      genotyped by RFLP-PCR (44 from human patients and eight from dogs). The results
      showed nine distinct patterns. The majority of the genotyped samples were from
      Sorocaba (30), and the others were distributed among 14 other municipalities. The
      first pattern was more frequent (29 samples), followed by pattern 2 (nine
      samples) and pattern 3 (three samples). Patterns 4, 6, 7, 8 and 9 were composed
      of two samples each and pattern 5 of one sample. CONCLUSION: These results
      suggest that polymorphic strains of L. (V.) braziliensis circulate in the state
      of Sao Paulo. These data agree with studies from other regions of Brazil, showing
      great variability among the natural populations of endemic foci.

PMID- 26200969
TI  - SEASONAL DISTRIBUTION OF MALARIA VECTORS (DIPTERA: CULICIDAE) IN RURAL LOCALITIES
      OF PORTO VELHO, RONDONIA, BRAZILIAN AMAZON.
AB  - We conducted a survey of the malaria vectors in an area where a power line had
      been constructed, between the municipalities of Porto Velho and Rio Branco, in
      the states of Rondonia and Acre, respectively. The present paper relates to the
      results of the survey of Anopheles fauna conducted in the state of Rondonia.
      Mosquito field collections were performed in six villages along the federal
      highway BR 364 in the municipality of Porto Velho, namely Porto Velho, Jaci
      Parana, Mutum Parana, Vila Abuna, Vista Alegre do Abuna, and Extrema. Mosquito
      captures were performed at three distinct sites in each locality during the
      months of February, July, and October 2011 using a protected human-landing catch
      method; outdoor and indoor captures were conducted simultaneously at each site
      for six hours. In the six sampled areas, we captured 2,185 mosquitoes belonging
      to seven Anopheles species. Of these specimens, 95.1% consisted of Anopheles
      darlingi, 1.8% An. triannulatus l.s., 1.7% An. deaneorum, 0.8% An. konderi l.s.,
      0.4 An. braziliensis, 0.1% An. albitarsis l.s., and 0.1% An. benarrochi. An.
      darlingi was the only species found in all localities; the remaining species
      occurred in sites with specific characteristics.

PMID- 26200970
TI  - CHICKEN COOPS, Triatoma dimidiata INFESTATION AND ITS INFECTION WITH Trypanosoma
      cruzi IN A RURAL VILLAGE OF YUCATAN, MEXICO.
AB  - This study longitudinally investigated the association between Triatoma dimidiata
      infestation, triatomine infection with Trypanosoma cruzi and household/backyard
      environmental characteristics in 101 homesteads in Molas and Yucatan, Mexico,
      between November 2009 (rainy season) and May 2010 (dry season). Logistic
      regression models tested the associations between insect infestation/infection
      and potential household-level risk factors. A total of 200 T. dimidiata were
      collected from 35.6% of the homesteads, mostly (73%) from the peridomicile. Of
      all the insects collected, 48% were infected with T. cruzi. Infected insects were
      collected in 31.6% of the homesteads (54.1% and 45.9% intra- and peridomiciliary,
      respectively). Approximately 30% of all triatomines collected were found in
      chicken coops. The presence of a chicken coop in the backyard of a homestead was
      significantly associated with both the odds of finding T. dimidiata (OR = 4.10,
      CI 95% = 1.61-10.43, p = 0.003) and the presence of triatomines infected with T.
      cruzi (OR = 3.37, CI 95% = 1.36-8.33, p = 0.006). The results of this study
      emphasize the relevance of chicken coops as a putative source of T. dimidiata
      populations and a potential risk for T. cruzi transmission. 

PMID- 26200971
TI  - TUBERCULOSIS INFECTION MIGHT INCREASE THE RISK OF INVASIVE CANDIDIASIS IN AN
      IMMUNOCOMPETENT PATIENT.
AB  - Deep Candida infections commonly occur in immunosuppressed patients. A rare case
      of a multiple deep organ infection with Candida albicans and spinal tuberculosis
      was reported in a healthy young man. The 19-year-old man complained of month-long
      fever and lower back pain. He also had a history of scalded mouth syndrome.
      Coinfection with Mycobacterium tuberculosis and Candida albicans was diagnosed
      using the culture of aspirates from different regions. Symptoms improved
      considerably after antifungal and antituberculous therapy. This case illustrates
      that infection with tuberculosis might impair the host's immune system and
      increase the risk of invasive candidiasis in an immunocompetent patient. 

PMID- 26200972
TI  - WEST NILE FEVER IN BRAZIL: SPORADIC CASE, SILENT ENDEMIC DISEASE OR EPIDEMIC IN
      ITS INITIAL STAGES?

PMID- 26200974
TI  - Establishing a Global Vaccine-Development Fund.

PMID- 26200975
TI  - The Expansion of Retail Clinics--Corporate Titans vs. Organized Medicine.

PMID- 26200973
TI  - Perspectives on next steps in classification of oro-facial pain - Part 3:
      biomarkers of chronic oro-facial pain - from research to clinic.
AB  - The purpose of this study was to review the current status of biomarkers used in
      oro-facial pain conditions. Specifically, we critically appraise their relative
      strengths and weaknesses for assessing mechanisms associated with the oro-facial
      pain conditions and interpret that information in the light of their current
      value for use in diagnosis. In the third section, we explore biomarkers through
      the perspective of ontological realism. We discuss ontological problems of
      biomarkers as currently widely conceptualised and implemented. This leads to
      recommendations for research practice aimed to a better understanding of the
      potential contribution that biomarkers might make to oro-facial pain diagnosis
      and thereby fulfil our goal for an expanded multidimensional framework for oro
      facial pain conditions that would include a third axis. 

PMID- 26200976
TI  - Transplanting Hepatitis C-Positive Kidneys.

PMID- 26200979
TI  - Long-Term Outcomes of Abdominal Aortic Aneurysm in the Medicare Population.
AB  - BACKGROUND: Randomized trials and observational studies have shown that
      perioperative morbidity and mortality are lower with endovascular repair of
      abdominal aortic aneurysm than with open repair, but the survival benefit is not
      sustained. In addition, concerns have been raised about the long-term risk of
      aneurysm rupture or the need for reintervention after endovascular repair.
      METHODS: We assessed perioperative and long-term survival, reinterventions, and
      complications after endovascular repair as compared with open repair of abdominal
      aortic aneurysm in propensity-score-matched cohorts of Medicare beneficiaries who
      underwent repair during the period from 2001 through 2008 and were followed
      through 2009. RESULTS: We identified 39,966 matched pairs of patients who had
      undergone either open repair or endovascular repair. The overall perioperative
      mortality was 1.6% with endovascular repair versus 5.2% with open repair
      (P<0.001). From 2001 through 2008, perioperative mortality decreased by 0.8
      percentage points among patients who underwent endovascular repair (P=0.001) and
      by 0.6 percentage points among patients who underwent open repair (P=0.01). The
      rate of conversion from endovascular to open repair decreased from 2.2% in 2001
      to 0.3% in 2008 (P<0.001). The rate of survival was significantly higher after
      endovascular repair than after open repair through the first 3 years of follow
      up, after which time the rates of survival were similar. Through 8 years of
      follow-up, interventions related to the management of the aneurysm or its
      complications were more common after endovascular repair, whereas interventions
      for complications related to laparotomy were more common after open repair.
      Aneurysm rupture occurred in 5.4% of patients after endovascular repair versus
      1.4% of patients after open repair through 8 years of follow-up (P<0.001). The
      rate of total reinterventions at 2 years after endovascular repair decreased over
      time (from 10.4% among patients who underwent procedures in 2001 to 9.1% among
      patients who underwent procedures in 2007). CONCLUSIONS: Endovascular repair, as
      compared with open repair, of abdominal aortic aneurysm was associated with a
      substantial early survival advantage that gradually decreased over time. The rate
      of late rupture was significantly higher after endovascular repair than after
      open repair. The outcomes of endovascular repair have been improving over time.
      (Funded by the National Institutes of Health.).

PMID- 26200978
TI  - Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer.
AB  - BACKGROUND: The effect of internal mammary and medial supraclavicular lymph-node
      irradiation (regional nodal irradiation) added to whole-breast or thoracic-wall
      irradiation after surgery on survival among women with early-stage breast cancer
      is unknown. METHODS: We randomly assigned women who had a centrally or medially
      located primary tumor, irrespective of axillary involvement, or an externally
      located tumor with axillary involvement to undergo either whole-breast or
      thoracic-wall irradiation in addition to regional nodal irradiation (nodal
      irradiation group) or whole-breast or thoracic-wall irradiation alone (control
      group). The primary end point was overall survival. Secondary end points were the
      rates of disease-free survival, survival free from distant disease, and death
      from breast cancer. RESULTS: Between 1996 and 2004, a total of 4004 patients
      underwent randomization. The majority of patients (76.1%) underwent breast
      conserving surgery. After mastectomy, 73.4% of the patients in both groups
      underwent chest-wall irradiation. Nearly all patients with node-positive disease
      (99.0%) and 66.3% of patients with node-negative disease received adjuvant
      systemic treatment. At a median follow-up of 10.9 years, 811 patients had died.
      At 10 years, overall survival was 82.3% in the nodal-irradiation group and 80.7%
      in the control group (hazard ratio for death with nodal irradiation, 0.87; 95%
      confidence interval [CI], 0.76 to 1.00; P=0.06). The rate of disease-free
      survival was 72.1% in the nodal-irradiation group and 69.1% in the control group
      (hazard ratio for disease progression or death, 0.89; 95% CI, 0.80 to 1.00;
      P=0.04), the rate of distant disease-free survival was 78.0% versus 75.0% (hazard
      ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02), and breast-cancer mortality was 12.5%
      versus 14.4% (hazard ratio, 0.82; 95% CI, 0.70 to 0.97; P=0.02). Acute side
      effects of regional nodal irradiation were modest. CONCLUSIONS: In patients with
      early-stage breast cancer, irradiation of the regional nodes had a marginal
      effect on overall survival. Disease-free survival and distant disease-free
      survival were improved, and breast-cancer mortality was reduced. (Funded by Fonds
      Cancer; ClinicalTrials.gov number, NCT00002851.).

PMID- 26200980
TI  - AVI-7288 for Marburg Virus in Nonhuman Primates and Humans.
AB  - BACKGROUND: AVI-7288 is a phosphorodiamidate morpholino oligomer with positive
      charges that targets the viral messenger RNA that encodes Marburg virus (MARV)
      nucleoprotein. Its safety in humans is undetermined. METHODS: We assessed the
      efficacy of AVI-7288 in a series of studies involving a lethal challenge with
      MARV in nonhuman primates. The safety of AVI-7288 was evaluated in a randomized,
      multiple-ascending-dose study in which 40 healthy humans (8 humans per dose
      group) received 14 once-daily infusions of AVI-7288 (1 mg, 4 mg, 8 mg, 12 mg, or
      16 mg per kilogram of body weight) or placebo, in a 3:1 ratio. We estimated the
      protective dose in humans by comparing pharmacokinetic variables in infected
      nonhuman primates, uninfected nonhuman primates, and uninfected humans. RESULTS:
      Survival in infected nonhuman primates was dose-dependent, with survival rates of
      0%, 30%, 59%, 87%, 100%, and 100% among monkeys treated with 0 mg, 3.75 mg, 7.5
      mg, 15 mg, 20 mg, and 30 mg of AVI-7288 per kilogram, respectively (P<0.001 with
      the use of the log-rank test for the comparison of survival across groups). No
      safety concern was identified at doses up to 16 mg per kilogram per day in
      humans. No serious adverse events were reported. Drug exposure (the area under
      the curve) was dose-dependent in both nonhuman primates and humans; drug
      clearance was independent of dose but was higher in nonhuman primates than in
      humans. The protective dose in humans was initially estimated, on the basis of
      exposure, to be 9.6 mg per kilogram per day (95% confidence interval, 6.6 to
      12.5) for 14 days. Monte Carlo simulations supported a dose of 11 mg per kilogram
      per day to match the geometric mean protective exposure in nonhuman primates.
      CONCLUSIONS: This study shows that, on the basis of efficacy in nonhuman primates
      and pharmacokinetic data in humans, AVI-7288 has potential as postexposure
      prophylaxis for MARV infection in humans. (Funded by the Department of Defense;
      ClinicalTrials.gov number, NCT01566877.).

PMID- 26200981
TI  - Interventional Approaches to Gallbladder Disease.

PMID- 26200977
TI  - Regional Nodal Irradiation in Early-Stage Breast Cancer.
AB  - BACKGROUND: Most women with breast cancer who undergo breast-conserving surgery
      receive whole-breast irradiation. We examined whether the addition of regional
      nodal irradiation to whole-breast irradiation improved outcomes. METHODS: We
      randomly assigned women with node-positive or high-risk node-negative breast
      cancer who were treated with breast-conserving surgery and adjuvant systemic
      therapy to undergo either whole-breast irradiation plus regional nodal
      irradiation (including internal mammary, supraclavicular, and axillary lymph
      nodes) (nodal-irradiation group) or whole-breast irradiation alone (control
      group). The primary outcome was overall survival. Secondary outcomes were disease
      free survival, isolated locoregional disease-free survival, and distant disease
      free survival. RESULTS: Between March 2000 and February 2007, a total of 1832
      women were assigned to the nodal-irradiation group or the control group (916
      women in each group). The median follow-up was 9.5 years. At the 10-year follow
      up, there was no significant between-group difference in survival, with a rate of
      82.8% in the nodal-irradiation group and 81.8% in the control group (hazard
      ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of
      disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the
      control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the
      nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis
      (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). CONCLUSIONS:
      Among women with node-positive or high-risk node-negative breast cancer, the
      addition of regional nodal irradiation to whole-breast irradiation did not
      improve overall survival but reduced the rate of breast-cancer recurrence.
      (Funded by the Canadian Cancer Society Research Institute and others; MA.20
      ClinicalTrials.gov number, NCT00005957.).

PMID- 26200982
TI  - IMAGES IN CLINICAL MEDICINE. Neck Impalement during Mountain Biking.

PMID- 26200983
TI  - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 23-2015. A 51-Year-Old
      Woman with Headache, Cognitive Impairment, and Weakness.

PMID- 26200984
TI  - Nodal Irradiation after Breast-Cancer Surgery in the Era of Effective Adjuvant
      Therapy.

PMID- 26200985
TI  - Convenient Ambulatory Care--Promise, Pitfalls, and Policy.

PMID- 26200986
TI  - Targeting Antithrombin to Treat Hemophilia.

PMID- 26200987
TI  - PET-Directed Therapy for Hodgkin's Lymphoma.

PMID- 26200988
TI  - PET-Directed Therapy for Hodgkin's Lymphoma.

PMID- 26200989
TI  - Inflammatory Muscle Diseases.

PMID- 26200990
TI  - Inflammatory Muscle Diseases.

PMID- 26200991
TI  - Inflammatory Muscle Diseases.

PMID- 26200992
TI  - IMAGES IN CLINICAL MEDICINE. Cervical Meningocele.

PMID- 26200993
TI  - Transition to adult mental health services for young people with attention
      deficit hyperactivity disorder in Italy: Parents' and clinicians' experiences.
AB  - OBJECTIVE: The aim of this study was to describe the experiences of parents and
      clinicians in relation to the transition from child and adolescent
      neuropsychiatric services (CANPS) to adult services for people with attention
      deficit hyperactivity disorder (ADHD) in Italy. METHODS: Parents of people with
      ADHD who reached the transition boundary for CANPS were sampled from the A.I.F.A.
      association (Italian Association of ADHD Families). We thematically analyzed
      informative and qualitative questionnaires completed by parents and clinicians.
      RESULTS: Parents' (n = 24) and clinicians' (n = 27) experiences differed slightly
      on challenges and unmet needs, whereas clinicians agreed on the variables
      required for an optimal transition process. Poor transition and multiple barriers
      to such care were identified. Specifically, far fewer people received services,
      especially public health services, after reaching the age of 18, and perceived
      barriers included problems with user access, limited transition protocols, poor
      service coordination, and possible lack of ADHD-related knowledge on the part of
      adult practitioners. CONCLUSIONS: Care continuity in mental healthcare remains a
      need to be prioritized and better defined also for ADHD patients (and their
      parents). Parents' and clinicians' experiences are more likely to be positive if
      transition management is characterized by a gradual preparation, a period of
      parallel care, and commonly acknowledged, clear information on available services
      and how to access them. Identifying the needs and barriers of the people
      representing the different roles (clinicians, parents, and users) involved in the
      transition to adult mental health services is of particular importance in
      designing effective, shared transfer planning procedures.

PMID- 26200995
TI  - The Natural History of Indeterminate Blunt Cerebrovascular Injury.
AB  - IMPORTANCE: The Denver criteria grade blunt cerebrovascular injuries (BCVIs) but
      fail to capture many patients with indeterminate findings on initial imaging.
      OBJECTIVE: To evaluate outcomes and clinical significance of indeterminate BCVIs
      (iBCVIs). DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of all
      patients treated for BCVIs at our institution from January 1, 2007, through July
      31, 2014, was completed. Patients were divided into 2 groups: those with true
      BCVIs as defined by the Denver criteria and those with iBCVIs, which was any
      initial imaging suggestive of a cerebrovascular arterial injury not classifiable
      by the Denver criteria. MAIN OUTCOMES AND MEASURES: Primary outcomes were rate of
      resolution of iBCVIs, freedom from cerebrovascular accident (CVA) or transient
      ischemic attack (TIA), and 30-day mortality. RESULTS: We identified 100 patients
      with 138 BCVIs: 79 with true BCVIs and 59 with iBCVIs. With serial imaging, 23
      iBCVIs (39.0%) resolved and 21 (35.6%) remained indeterminate, whereas 15 (25.4%)
      progressed to true BCVI. The rate of CVA or TIA in the iBCVI group was 5.1%
      compared with 15.2% in the true BCVI group (P = .06). Of the 15 total CVAs or
      TIAs, 11 (73.3%) resulted from carotid injury and 4 (26.7%) from vertebral artery
      occlusion (P = .03). By Kaplan-Meier analysis, there was no difference in freedom
      from CVA or TIA for the 2 groups (P = .07). Median clinical follow-up was 91
      days. Overall and 30-day mortality for the entire series were 17.4% and 15.2%,
      respectively. There was no difference in long-term or 30-day mortality between
      true BCVI and iBCVI groups. CONCLUSIONS AND RELEVANCE: Detection of iBCVI has
      become a common clinical conundrum with improved and routine imaging.
      Indeterminate BCVI is not completely benign, with 25.4% demonstrating anatomical
      progression to true BCVI and 5.1% developing cerebrovascular symptoms. We
      therefore recommend serial imaging and antiplatelet therapy for iBCVI.

PMID- 26200999
TI  - Discussion and Research on Provincial Difference in Rural Finance in China Under
      the Perspective of Financial Geography: Retraction.

PMID- 26200994
TI  - Association between Glucose Metabolism and Sleep-disordered Breathing during REM
      Sleep.
AB  - RATIONALE: Sleep-disordered breathing (SDB) has been associated with impaired
      glucose metabolism. It is possible that the association between SDB and glucose
      metabolism is distinct for non-REM versus REM sleep because of differences in
      sleep-state-dependent sympathetic activation and/or degree of hypoxemia.
      OBJECTIVES: To characterize the association between REM-related SDB, glucose
      intolerance, and insulin resistance in a community-based sample. METHODS: A cross
      sectional analysis that included 3,310 participants from the Sleep Heart Health
      Study was undertaken (53% female; mean age, 66.1 yr). Full montage home
      polysomnography and fasting glucose were available on all participants. SDB
      severity during REM and non-REM sleep was quantified using the apnea-hypopnea
      index in REM (AHIREM) and non-REM sleep (AHINREM), respectively. Fasting and 2
      hour post-challenge glucose levels were assessed during a glucose tolerance test
      (n = 2,264). The homeostatic model assessment index for insulin resistance (HOMA
      IR) was calculated (n = 1,543). Linear regression was used to assess the
      associations of AHIREM and AHINREM with fasting and post-prandial glucose levels
      and HOMA-IR. MEASUREMENTS AND MAIN RESULTS: AHIREM and AHINREM were associated
      with fasting glycemia, post-prandial glucose levels, and HOMA-IR in models that
      adjusted for age, sex, race, and site. However, with additional adjustment for
      body mass index, waist circumference, and sleep duration, AHIREM was only
      associated with HOMA-IR (beta = 0.04; 95% CI, 0.1-0.07; P = 0.01), whereas
      AHINREM was only associated with fasting (beta = 0.93; 95% CI, 0.14-1.72; P =
      0.02) and post-prandial glucose levels (beta = 3.0; 95% CI, 0.5-5.5; P = 0.02).
      CONCLUSIONS: AHIREM is associated with insulin resistance but not with fasting
      glycemia or glucose intolerance.

PMID- 26201000
TI  - Ecosystem Services Flows: Why Stakeholders' Power Relationships Matter.
AB  - The ecosystem services framework has enabled the broader public to acknowledge
      the benefits nature provides to different stakeholders. However, not all
      stakeholders benefit equally from these services. Rather, power relationships are
      a key factor influencing the access of individuals or groups to ecosystem
      services. In this paper, we propose an adaptation of the "cascade" framework for
      ecosystem services to integrate the analysis of ecological interactions among
      ecosystem services and stakeholders' interactions, reflecting power relationships
      that mediate ecosystem services flows. We illustrate its application using the
      floodplain of the River Piedra (Spain) as a case study. First, we used structural
      equation modelling (SEM) to model the dependence relationships among ecosystem
      services. Second, we performed semi-structured interviews to identify formal
      power relationships among stakeholders. Third, we depicted ecosystem services
      according to stakeholders' ability to use, manage or impair ecosystem services in
      order to expose how power relationships mediate access to ecosystem services. Our
      results revealed that the strongest power was held by those stakeholders who
      managed (although did not use) those keystone ecosystem properties and services
      that determine the provision of other services (i.e., intermediate regulating and
      final services). In contrast, non-empowered stakeholders were only able to access
      the remaining non-excludable and non-rival ecosystem services (i.e., some of the
      cultural services, freshwater supply, water quality, and biological control). In
      addition, land stewardship, access rights, and governance appeared as critical
      factors determining the status of ecosystem services. Finally, we stress the need
      to analyse the role of stakeholders and their relationships to foster equal
      access to ecosystem services. 

PMID- 26201001
TI  - Peripheral arterial disease in heterozygous familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia is characterized by elevated plasma
      cholesterol and early coronary arterial disease onset. However, few studies
      investigated the association of heterozygous familial hypercholesterolemia with
      peripheral arterial disease. METHODS: In a cross sectional study 202 heterozygous
      familial hypercholesterolemia patients (91% confirmed by molecular diagnosis)
      were compared to 524 normolipidemic controls. Peripheral arterial disease was
      diagnosed by ankle-brachial index values <=0.90. RESULTS: Compared with controls,
      familial hypercholesterolemia patients were older, more often female, with higher
      rates of hypertension, diabetes, previous coronary disease and higher total
      cholesterol levels. Smoking (previous and former) was more common among controls.
      The prevalence of peripheral arterial disease was 17.3 and 2.3% respectively in
      familial hypercholesterolemia and controls (p < 0.001). Results persisted after
      matching familial hypercholesterolemia and controls by a propensity score.
      Regression analyses demonstrated that age (odds ratio- OR = 1.03 95% CI 1.00
      1.05, p = 0.033), previous cardiovascular disease (OR = 3.12 CI 95% 1.56-6.25, p
      = 0.001) and familial hypercholesterolemia diagnosis (OR = 5.55 CI 95% 2.69
      11.44, p< 0.001) were independently associated with peripheral arterial disease.
      Among familial hypercholesterolemia patients, age (OR 1.05, 95% CI 1.02-1.09, p =
      0.005), intermittent claudication (OR 6.32, 95% CI 2.60-15.33, p< 0.001) and
      smoking (OR 2.44, 95% CI 1.08-5.52, p = 0.032) were associated with peripheral
      arterial disease. CONCLUSIONS: Peripheral arterial disease is more frequent in
      familial hypercholesterolemia than in normolipidemic subjects and it should
      routine screened in these individuals even if asymptomatic. However, its role as
      predictor of cardiovascular events needs to be ascertained prospectively.

PMID- 26201003
TI  - Effects of intermittent exercise on biomarkers of cardiovascular risk in night
      shift workers.
AB  - OBJECTIVE: Cathepsin L (CatL), cathepsin S (CatS), and arteriosclerosis adhesion
      molecules such as monocyte chemotactic protein-1 (MCP-1), soluble vascular cell
      adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) are potent
      elastases implicated in human arterial wall remodeling. In this study, we aimed
      to evaluate the effects of intermittent exercise on the plasma concentrations of
      these cathepsins and arteriosclerosis adhesion molecules in night shift workers.
      METHODS: Thirty male participants who were night shift workers (experimental
      group, n = 15; control group, n = 15) were included in this study. The
      experimental group performed an intermittent exercise at 10-min bouts (30 min per
      day), three days a week during 10 weeks. Body composition, blood pressure, and
      cardiovascular disease risk factors were measured. RESULTS: After intermittent
      exercise, significant group time interactions for body weight (p < .01) and body
      fat percentage (p < .01) were found. With regard to cardiovascular disease risk
      factors, group time interactions for CatL (p < .01), CatS (p < .01), MCP-1 (p <
      .05), sE-selectin (p < .01), and sVCAM-1 (p < .01) were significant. CONCLUSIONS:
      This study provides preliminary evidence to suggest that intermittent exercise
      may represent an effective intervention strategy for preventing atherosclerosis,
      thus leading to improved cardiovascular health in night shift workers.

PMID- 26201002
TI  - Is the association of serum sodium with mortality in patients with type 2
      diabetes explained by copeptin or NT-proBNP? (ZODIAC-46).
AB  - BACKGROUND AND AIMS: Hyponatremia has been associated with an increased mortality
      risk in the general population. Diabetes is a condition predisposing for elevated
      levels of arginine vasopressin (AVP) and heart failure, both common causes of
      hyponatremia. These factors, however, are also associated with an increased
      mortality risk. We aimed to investigate whether serum sodium is associated with
      cardiovascular and all-cause mortality in type 2 diabetes and whether these
      associations could be explained by copeptin, a surrogate for AVP, or NT-proBNP, a
      marker for heart failure. METHODS: Patients with type 2 diabetes participating in
      the observational ZODIAC study were included. Cox regression analyses were used
      to investigate the association of serum sodium with mortality. RESULTS: We
      included 1068 patients (age 67 +/- 12 years, 45% male, serum sodium 142 +/- 3
      mmol/L). After 15 years of follow-up, 519 patients (49%) died, with 225
      cardiovascular deaths (21%). In univariable analyses, serum sodium, copeptin, and
      NT-proBNP were all significantly associated with cardiovascular and all-cause
      mortality. These associations remained significant after combination of these
      markers in a multivariable model. Serum sodium and NT-proBNP remained
      significantly associated with mortality after further adjustment for potential
      confounders, whereas copeptin lost significance after adjustment for SCr and ACR.
      CONCLUSION: Low serum sodium was associated with an increased risk of
      cardiovascular and all-cause mortality in type 2 diabetes. Moreover, these
      associations were not explained by copeptin and NT-proBNP. Whether low serum
      sodium itself leads to poor outcome or is a marker for (unidentified) co
      morbidity severity or use of specific medications remains to be elucidated.

PMID- 26201004
TI  - Design of Single-Molecule Magnets: Insufficiency of the Anisotropy Barrier as the
      Sole Criterion.
AB  - Determination of the electronic energy spectrum of a trigonal-symmetry
      mononuclear Yb(3+) single-molecule magnet (SMM) by high-resolution absorption and
      luminescence spectroscopies reveals that the first excited electronic doublet is
      placed nearly 500 cm(-1) above the ground one. Fitting of the paramagnetic
      relaxation times of this SMM to a thermally activated (Orbach) model {tau = tau0
      * exp[DeltaOrbach/(kBT)]} affords an activation barrier, DeltaOrbach, of only 38
      cm(-1). This result is incompatible with the spectroscopic observations. Thus, we
      unambiguously demonstrate, solely on the basis of experimental data, that Orbach
      relaxation cannot a priori be considered as the main mechanism determining the
      spin dynamics of SMMs. This study highlights the fact that the general synthetic
      approach of optimizing SMM behavior by maximization of the anisotropy barrier,
      intimately linked to the ligand field, as the sole parameter to be tuned, is
      insufficient because of the complete neglect of the interaction of the magnetic
      moment of the molecule with its environment. The Orbach mechanism is expected
      dominant only in the cases in which the energy of the excited ligand field state
      is below the Debye temperature, which is typically low for molecular crystals
      and, thus, prevents the use of the anisotropy barrier as a design criterion for
      the realization of high-temperature SMMs. Therefore, consideration of additional
      design criteria that address the presence of alternative relaxation processes
      beyond the traditional double-well picture is required. 

PMID- 26201005
TI  - Functional Impairments Mediate Association Between Clinical Fracture Risk and
      Type 2 Diabetes Mellitus in Older Women.
AB  - OBJECTIVES: To examine the effect of functional impairments in older women with
      diabetes mellitus (DM) on incident clinical fractures. DESIGN: Secondary analysis
      of two large prospective cohort studies. SETTING: North Carolina Established
      Populations for Epidemiologic Studies of the Elderly (EPESE) and Women's Health
      Initiative (WHI) clinical trials. PARTICIPANTS: EPESE included 2,704 community
      dwelling women aged 65 and older; WHI clinical trials included 68,125
      postmenopausal women. MEASUREMENTS: Women with DM at baseline were compared with
      women without in successive Cox proportional hazards models. Functional
      limitations were determined according to self-reported difficulties with
      activities of daily living (ADLs) and physical activities. RESULTS: The risk of
      any clinical fracture during the study period was greater in women with DM, after
      controlling for age, race and ethnicity, and body mass index, in the EPESE
      (hazard ratio (HR) = 1.36, 95% confidence interval (CI) = 1.08-1.72) and WHI (HR
      = 1.29, 95% CI = 1.19-1.39) cohorts. After inclusion of functional limitations,
      the greater risk of fracture associated with DM decreased in the EPESE (HR =
      1.25, 95% CI = 0.98-1.59) and WHI (HR = 1.21, 95% CI = 1.12-1.31) cohorts. In
      participants with DM, difficulties with moderate physical activities, such as
      bending or stooping, walking several blocks, and heavy housework, were
      significantly associated with incident fracture (P < .05). CONCLUSION: Older
      women with DM are at greater risk of clinical fractures than those without,
      independent of bone mineral density. Greater functional impairment in moderate
      physical activities mediates this greater fracture risk in part, although there
      remains an unexplained residual DM-associated risk for fracture.

PMID- 26201006
TI  - A P-Norm Robust Feature Extraction Method for Identifying Differentially
      Expressed Genes.
AB  - In current molecular biology, it becomes more and more important to identify
      differentially expressed genes closely correlated with a key biological process
      from gene expression data. In this paper, based on the Schatten p-norm and Lp
      norm, a novel p-norm robust feature extraction method is proposed to identify the
      differentially expressed genes. In our method, the Schatten p-norm is used as the
      regularization function to obtain a low-rank matrix and the Lp-norm is taken as
      the error function to improve the robustness to outliers in the gene expression
      data. The results on simulation data show that our method can obtain higher
      identification accuracies than the competitive methods. Numerous experiments on
      real gene expression data sets demonstrate that our method can identify more
      differentially expressed genes than the others. Moreover, we confirmed that the
      identified genes are closely correlated with the corresponding gene expression
      data. 

PMID- 26201007
TI  - Circulating levels of irisin is elevated in hypothyroidism, a case-control study.
AB  - Objective Our objective in this study was to determine the relationship between
      irisin hormone, which has a similar effect with thyroid hormones on adipose
      tissue and the metabolism, and the thyroid functions and the obesity secondary to
      thyroid disease. Subjects and methods Seventy-four patients were included in the
      study, of the patients, 37 were newly diagnosed with Hashimoto's thyroiditis
      related hypothyroidism but not started on a treatment yet, and the remaining 37
      were healthy volunteers without a known disease. Serum thyroid stimulating
      hormone (TSH), free thyroxin (fT4), anti-thyroglobulin and anti-thyroid
      peroxidase were measured and thyroid ultrasonography was performed in both
      groups. Serum irisin levels were measured using the commercially available ELISA
      kit. The hypothyroidism group had higher levels of irisin compared to the control
      group (2.77 ng/mL vs. 2.15 ng/mL respectively; p = 0.017). Results The
      hypothyroidism group had higher median levels of irisin in the obese patients
      than those in the control group (3.10 ng/mL vs. 2.10 ng/mL respectively; p =
      0.013). Irisin level was negatively correlated with age in the whole population
      and patients with hypothyroidism (r = -0.255, p = 0.028; r = -0.346, p = 0.036
      respectively). Irisin level was positively correlated with TSH (r = 0.247, p =
      0.034) but negatively correlated with the fT4 (r = -0.316, p = 0.006) in the
      whole population. Obesity, fT4 and irisin levels were identified to be
      independent predictors in the diagnosis of hypothyroidism in the multivariable
      logistic regression analysis. Conclusion To the best of our knowledge, this study
      is the first in literature to identify that obesity, irisin level and fT4 level
      are independent risk factors for hypothyroidism. 

PMID- 26201008
TI  - Arterial stiffness and endothelial inflammation in prediabetes and newly
      diagnosed diabetes patients.
AB  - OBJECTIVE: There is a growing body of data supporting the association between
      diabetes and microcirculatory disfunction. We aimed to study e-selectin levels,
      and their associations with serum markers of inflammation and arterial stiffness
      in prediabetes and newly diagnosed diabetes patients in this study. SUBJECTS AND
      METHODS: Sixty patients (25 females) with a newly established elevated fasting
      serum glucose [20 impaired fasting glucose (IFG), 20 impaired glucose tolerance
      (IGT), 20 newly diagnosed diabetes (T2DM)] and 17 healthy controls (13 females)
      were included in the study. Serum e-selectin and hs-CRP levels, and arterial
      stiffness parameters of the patients were studied. RESULTS: Fasting serum glucose
      was the most important predictor of serum e-selectin levels. Pulse wave velocity
      and central aortic pressures were significantly higher in IFG, IGT and T2DM
      groups, compared to controls (p = 0.001, < 0.001, 0.013 and 0.015, 0.002, 0.009,
      respectively). The mean arterial pressure did not show any significant
      association with serum e-selectin and hs-CRP levels (beta coefficient: 0.092, p =
      0.358; and beta coefficient: 0.189, p = 0.362, respectively). CONCLUSION:
      Prediabetes patients have increasing e-selectin levels through the diagnosis of
      T2DM. E-selectin is associated with serum glucose levels. Prediabetic and newly
      diagnosed diabetics have higher arterial stiffness measurements. Serum e-selectin
      may be a good marker of endothelial inflammation and dysfunction increasing in
      parallel with serum glucose levels, predicting future cardiovascular events.

PMID- 26201009
TI  - Relationship between mean platelet volume and vitamin D deficiency in gestational
      diabetes mellitus.
AB  - OBJECTIVE: To investigate whether vitamin D deficiency is associated with high
      mean platelet volume (MPV) in pregnancies diagnosed with gestational diabetes
      mellitus (GDM) compared to healthy pregnancies. SUBJECTS AND METHODS: This study
      included 200 pregnant women. 25-hydroxyvitamin D3(25(OH)D3) and MPV values were
      monitored between pregnant women with GDM and normal glucose metabolism.
      Correlation between 25(OH)D3 and MPV was calculated both in GDM and healthy
      pregnancies. Both 25(OH)D3 level in different MPV percentile (<= 50, 50-75, 75
      90, >= 90 percentile) and MPV value in different 25(OH)D3 level (<= 10, 10-20, >=
      20 ng/mL) were calculated. RESULTS: Low 25(OH)D3 level and high MPV were observed
      both in GDM group (p = 0.007, p = 0.06, respectively) and in glucose metabolism
      disorders (GMD) group (p = 0.03, p = 0.04, respectively). There was no
      significant relationship between 25(OH)D3 and MPV in healthy pregnancies.
      Whereas, it is observed that there is a negative, but statistically insignificant
      correlation between MPV and 25(OH)D3 pregnant women with GMD (r = 0.1, r = -0.7,
      respectively). MPV values had significantly higher in vitamin D deficient group
      than pregnant women with normal 25(OH)D3 level in GMD group (p = 0.04). The
      optimal 25(OH)D3 cut off point for predicting future cardiovascular risk was 10.4
      ng/ mL (area under curve (AUC) = 0.58). CONCLUSIONS: Vitamin D deficiency may
      contribute to an increased risk for future cardiovascular diseases and a risk of
      thrombotic complications in pregnant women with GDM.

PMID- 26201010
TI  - Postoperative calcium levels as a diagnostic measure for hypoparathyroidism after
      total thyroidectomy.
AB  - OBJECTIVE: The aim of the present study was to identify a fast, efficient and low
      cost method to diagnose hypoparathyroidism after total thyroidectomy. MATERIALS
      AND METHODS: One hundred and forty medical records, which contained patients'
      clinical and laboratory data, were retrospectively analyzed. Patient parathyroid
      hormone values, which were obtained immediately following operation, were
      compared with their ionized calcium levels the morning after surgery. This
      comparison was used to examine the correlation between the two variables in
      predicting hypoparathyroidism because measuring calcium levels is low-cost and
      more available in the hospitals compared to measuring parathormone (PTH) levels.
      RESULTS: There was a positive and statistically significant correlation between
      PTH and ionized calcium values (Pearson correlation coefficient, r = 0.456; p <
      0.0001). The values of first postoperative day ionized calcium levels (stratified
      by the 1.10 mmol/l cut-off value) were tested as a diagnostic measure for
      hypoparathyroidism, and a PTH < 15 pg/mL obtained immediately following operation
      served as a reference. This analysis showed that ionized calcium levels measured
      on the first postoperative day had a sensitivity of 45.6% (95% CI 30.9-61.0%), a
      specificity of 88.9% (95% CI 80.5-94.5%) and an accuracy of 76.7% (95% CI 68.7
      83.5%) as a diagnostic measure for hypoparathyroidism. CONCLUSION: In conclusion,
      we demonstrated that patients who had high ionized calcium levels on the first
      postoperative day also had high PTH levels immediately following operation and,
      therefore, they had lower rates of hypoparathyroidism.

PMID- 26201011
TI  - Design of an allele-specific PCR assay to genotype the rs12255372 SNP in a pilot
      study of association between common TCF7L2 polymorphisms and type 2 diabetes in
      Venezuelans.
AB  - OBJECTIVE: The global burden of diabetes mellitus will impact strongly American
      countries in the coming decades. Type 2 diabetes mellitus (T2DM) is a
      multifactorial disease and the basis for its genetic susceptibility remains not
      fully understood. Different population studies have demonstrated that variants of
      the TCF7L2 gene are strongly associated with an increased risk of T2DM. Moreover,
      institutions or countries with limited budget to conduct genetic research need
      cost effective methods for detecting DNA variants. SUBJECTS AND METHODS: We
      standardized a rapid and simple allele-specific PCR method for genotyping the
      rs12255372 single nucleotide polymorphism (SNP) in a pilot study exploring the
      association of three TCF7L2 polymorphisms (rs7903146, rs12255372 and DG10S478)
      with T2DM in 70 patients and 73 controls from Venezuela. RESULTS: The performance
      of the designed allele-specific PCR reaction for rs12255372 genotyping was
      reliable and accurate. Patients carrying the TCF7L2 rs7903146 T allele (CT + TT
      genotypes) and heterozygous CT genotype had a significantly higher risk for T2DM
      (OR = 2.9 and 2.3, respectively). Although rs12255372 and DG10S478 risk alleles
      predominated in T2DM group no statistical significance was found. CONCLUSIONS: We
      developed a novel allele-specific PCR method for easier and rapid detection of
      rs12255372 polymorphism without the use of expensive instrumentation and
      reagents. Our study in a relatively small sample of the Venezuelan population
      replicated the association of the rs7903146 SNP with T2DM. Further studies with
      larger sample size and more biochemical data should be conducted to explore the
      genetic basis of T2DM susceptibility in Venezuela.

PMID- 26201012
TI  - Palladium(II)-Catalyzed Tandem Oxidative Acetoxylation/ortho C-H
      Activation/Carbocyclization of Arylallenes.
AB  - Herein we report an example of tandem oxidative acetoxylation/carbocyclization of
      arylallenes 1 using Pd(OAc)2. The catalytic protocol is highly selective and
      provides access to new C-C and C-O bonds leading to a carbocyclization. The
      reaction proceeds via C-H activation by Pd. Mechanistic investigations show that
      the C-H activation is not the rate-limiting step and indicate that the reaction
      proceeds via acetoxylation of the allene. 

PMID- 26201013
TI  - Mental Defeat Is Associated With Suicide Intent in Patients With Chronic Pain.
AB  - OBJECTIVE: Mental defeat has been implicated in precipitating suicide with
      effects not explained by depression. It has also been found to be elevated in
      people who are most distressed and disabled by chronic pain. This study examined
      the role of mental defeat in predicting suicide intent among chronic pain
      patients and compared the predictive value of mental defeat with other
      established pain and psychological constructs. METHODS: Sixty-two chronic pain
      patients attended a semistructured interview to assess pain characteristics and
      suicidality (present and worst-ever) and completed self-report measures of
      anxiety, depression, hopelessness, self-efficacy, pain catastrophizing, and
      mental defeat. RESULTS: A total of 22.6% of people reported a history of suicide
      attempt (1 attempt=12.9%; >=2 attempts=9.7%). The wish to die was reportedly
      moderate to strong for 63.3% of those who attempted suicide. No significant
      correlations were found for hopelessness and self-efficacy with suicide intent in
      this sample. Hierarchical regression analyses suggested that pain intensity was a
      significant predictor of worst-ever suicidal intent (R=0.11), and mental defeat
      significantly improved the prediction even when the effect of pain intensity was
      accounted for (DeltaR=0.12). Anxiety, depression, and pain catastrophizing were
      significant correlates of suicide intent, but they did not add to the prediction
      of worst-ever suicide intent after the effect of pain intensity was controlled
      for. DISCUSSION: Mental defeat may be a key indicator for heightened suicide
      risk. Therapeutic interventions targeting mental defeat offer a novel avenue for
      reducing suicide risk in chronic pain patients.

PMID- 26201014
TI  - Psychological Interventions for Vaccine Injections in Young Children 0 to 3
      Years: Systematic Review of Randomized Controlled Trials and Quasi-Randomized
      Controlled Trials.
AB  - BACKGROUND: This systematic review evaluated the effectiveness of distraction for
      reducing infant distress during vaccinations in young children aged 0 to 3 years.
      DESIGN/METHODS: Database searches identified relevant randomized and quasi
      randomized controlled trials. Three separate clinical questions related to
      variants of the psychological strategy of distraction (directed video; directed
      toy; nondirected toy) were pursued. Distress was identified as the critical
      outcome to assess the benefits of distraction and extracted from relevant trials.
      Distress was analyzed by phase of procedure (distress preprocedure; distress
      acute; distress recovery; idiosyncratic phases based on some or all of the 3
      aforementioned phases). RESULTS: Ten studies were included in the review.
      Significant results are presented herein. For directed video distraction,
      moderate quality evidence suggested that distress was lowered in the treatment
      group standardized mean difference (SMD -0.68 lower [95% confidence interval
      (CI), -1.04 to -0.32]) for the acute+recovery phase as well as the preprocedure
      phase (SMD -0.49 lower [95% CI, -7.6 to -0.22]). For directed toy distraction,
      the analysis of low-quality evidence for a combined preprocedure+acute+recovery
      phase of distress (analysis n=81), suggested that distress was lowered in the
      treatment group (SMD -0.47 lower [95% CI, -0.91 to -0.02]). An effect for
      nondirected toy distraction was also seen, analyzing very-low-quality evidence,
      for the acute distress phase (n=290; SMD -0.93 lower [95% CI, -1.86 to 0.00]).
      CONCLUSION: Generally low-quality to very-low-quality evidence suggests that
      there may be an effect of directed (toy and video) and nondirected toy
      distraction for children aged 0 to 3 years, for certain phases of the
      vaccination.

PMID- 26201015
TI  - Process Interventions for Vaccine Injections: Systematic Review of Randomized
      Controlled Trials and Quasi-Randomized Controlled Trials.
AB  - BACKGROUND: This systematic review evaluated the effectiveness of process
      interventions (education for clinicians, parent presence, education of parents
      [before and on day of vaccination], and education of patients on day of
      vaccination) on reducing vaccination pain, fear, and distress and increasing the
      use of interventions during vaccination. DESIGN/METHODS: Databases were searched
      using a broad search strategy to identify relevant randomized and quasi
      randomized controlled trials. Critical outcomes were pain, fear, distress (when
      applicable), and use of pain management interventions. Data were extracted
      according to procedure phase (preprocedure, acute, recovery, combinations of
      these) and pooled using established methods. Analyses were conducted using
      standardized mean differences (SMD) and risk ratios (RR). RESULTS: Thirteen
      studies were included. Results were generally mixed. On the basis of low to very
      low-quality evidence, the following specific critical outcomes showed significant
      effects suggesting: (1) clinicians should be educated about vaccine injection
      pain management (use of interventions: SMD 0.66; 95% confidence interval [CI]:
      0.47, 0.85); (2) parents should be present (distress preprocedure: SMD -0.85; 95%
      CI: -1.35, -0.35); (3) parents should be educated before the vaccination day (use
      of intervention preprocedure: SMD 0.83; 95% CI: 0.25, 1.41 and RR, 2.08; 95% CI:
      1.51, 2.86; distress acute: SMD, -0.35; 95% CI: -0.57, -0.13); (4) parents should
      be educated on the vaccination day (use of interventions: SMD 1.02; 95% CI: 0.22,
      1.83 and RR, 2.42; 95% CI: 1.47, 3.99; distress preprocedure+acute+recovery: SMD 
      0.48; 95% CI: -0.82, -0.15); and (5) individuals 3 years of age and above should
      be educated on the day of vaccination (fear preprocedure: SMD -0.67; 95% CI: 
      1.28, -0.07). CONCLUSIONS: Educating individuals involved in the vaccination
      procedure (clinicians, parents of children being vaccinated; individuals above 3
      y of age) is beneficial to increase use of pain management strategies, reduce
      distress surrounding with vaccination, and to reduce fear. When possible, parent
      presence is also recommended for children undergoing vaccination.

PMID- 26201017
TI  - Effect of Restricting Access to Health Care on Health Expenditures among Asylum
      Seekers and Refugees: A Quasi-Experimental Study in Germany, 1994-2013.
AB  - BACKGROUND: Access to health care for asylum-seekers and refugees (AS&R) in
      Germany is initially restricted before regular access is granted, allegedly
      leading to delayed care and increasing costs of care. We analyse the effects of
      (a) restricted access; and (b) two major policy reforms (1997, 2007) on incident
      health expenditures for AS&R in 1994-2013. METHODS AND FINDINGS: We used annual,
      nation-wide, aggregate data of the German Federal Statistics Office (1994-2013)
      to compare incident health expenditures among AS&R with restricted access
      (exposed) to AS&R with regular access (unexposed). We calculated incidence rate
      differences (?IRt) and rate ratios (IRRt), as well as attributable fractions
      among the exposed (AFe) and the total population (AFp). The effects of between
      group differences in need, and of policy reforms, on differences in per capita
      expenditures were assessed in (segmented) linear regression models. The exposed
      and unexposed groups comprised 4.16 and 1.53 million person-years. Per capita
      expenditures (1994-2013) were higher in the group with restricted access in
      absolute (?IRt = 375.80 Euros [375.77; 375.89]) and relative terms (IRR = 1.39).
      The AFe was 28.07% and the AFp 22.21%. Between-group differences in mean age and
      in the type of accommodation were the main independent predictors of between
      group expenditure differences. Need variables explained 50-75% of the variation
      in between-group differences over time. The 1997 policy reform significantly
      increased ?IRt adjusted for secular trends and between-group differences in age
      (by 600.0 Euros [212.6; 986.2]) and sex (by 867.0 Euros [390.9; 1342.5]). The
      2007 policy reform had no such effect. CONCLUSION: The cost of excluding AS&R
      from health care appears ultimately higher than granting regular access to care.
      Excess expenditures attributable to the restriction were substantial and could
      not be completely explained by differences in need. An evidence-informed
      discourse on access to health care for AS&R in Germany is needed; it urgently
      requires high-quality, individual-level data.

PMID- 26201018
TI  - Anion-exchange nanospheres as titration reagents for anionic analytes.
AB  - We present here anion-exchange nanospheres as novel titration reagents for
      anions. The nanospheres contain a lipophilic cation for which the counterion is
      initially Cl(-). Ion exchange takes place between Cl(-) in the nanospheres and a
      more lipophilic anion in the sample, such as ClO4(-) and NO3(-). Consecutive
      titration in the same sample solution for ClO4(-) and NO3(-) were demonstrated.
      As an application, the concentration of NO3(-) in spinach was successfully
      determined using this method. 

PMID- 26201016
TI  - Pharmacological and Combined Interventions to Reduce Vaccine Injection Pain in
      Children and Adults: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: This systematic review assessed the effectiveness and safety of
      pharmacotherapy and combined interventions for reducing vaccine injection pain in
      individuals across the lifespan. DESIGN/METHODS: Electronic databases were
      searched for relevant randomized and quasi-randomized controlled trials. Self
      reported pain and fear as well as observer-rated distress were critically
      important outcomes. Data were combined using standardized mean difference (SMD)
      or relative risk with 95% confidence intervals (CI). RESULTS: Fifty-five studies
      that examined breastfeeding (which combines sweet-tasting solution, holding, and
      sucking), topical anesthetics, sweet-tasting solutions (sucrose, glucose),
      vapocoolants, oral analgesics, and combination of 2 versus 1 intervention were
      included. The following results report findings of analyses of critical outcomes
      with the largest number of participants. Compared with control, acute distress
      was lower for infants breastfed: (1) during vaccination (n=792): SMD -1.78 (CI, 
      2.35, -1.22) and (2) before vaccination (n=100): SMD -1.43 (CI, -2.14, -0.72).
      Compared with control/placebo, topical anesthetics showed benefit on acute
      distress in children (n=1424): SMD -0.91 (CI, -1.36, -0.47) and self-reported
      pain in adults (n=60): SMD -0.85 (CI, -1.38, -0.32). Acute and recovery distress
      was lower for children who received sucrose (n=2071): SMD -0.76 (CI, -1.19, 
      0.34) or glucose (n=818): SMD -0.69 (CI, -1.03, -0.35) compared with placebo/no
      treatment. Vapocoolants reduced acute pain in adults [(n=185), SMD -0.78 (CI, 
      1.08, -0.48)] but not children. Evidence from other needle procedures showed no
      benefit of acetaminophen or ibuprofen. The administration of topical anesthetics
      before and breastfeeding during vaccine injections showed mixed results when
      compared with topical anesthetics alone. There were no additive benefits of
      combining glucose and non-nutritive sucking (pacifier) compared with glucose or
      non-nutritive sucking (pacifier) alone or breastfeeding and sucrose compared with
      breastfeeding or sucrose alone. CONCLUSIONS: Breastfeeding, topical anesthetics,
      sweet-tasting solutions, and combination of topical anesthetics and breastfeeding
      demonstrated evidence of benefit for reducing vaccine injection pain in infants
      and children. In adults, limited data demonstrate some benefit of topical
      anesthetics and vapocoolants.

PMID- 26201019
TI  - Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of
      coronary artery disease.
AB  - Long non-coding RNAs (lncRNAs) have been reported to be involved in the
      pathogenesis of cardiovascular disease (CVD), but whether circulating lncRNAs can
      serve as a coronary artery disease (CAD), biomarker is not known. The present
      study screened lncRNAs by microarray analysis in the plasma from CAD patients and
      control individuals and found that 265 lncRNAs were differentially expressed. To
      find specific lncRNAs as possible CAD biomarker candidates, we used the following
      criteria for 174 up-regulated lncRNAs: signal intensity >=8, fold change >2.5 and
      P<0.005. According to these criteria, five intergenic lncRNAs were identified.
      After validation by quantitative PCR (qPCR), one lncRNA was excluded from the
      candidate list. The remaining four lncRNAs were independently validated in
      another population of 20 CAD patients and 20 control individuals. Receiver
      operating characteristic (ROC) curve analysis showed that lncRNA AC100865.1
      (referred to as CoroMarker) was the best of these lncRNAs. CoroMarker levels were
      also stable in plasma. The predictive value of CoroMarker was further assessed in
      a larger cohort with 221 CAD patients and 187 control individuals. Using a
      diagnostic model with Fisher's criteria, taking the risk factors into account,
      the optimal sensitivity of CoroMarker for CAD increased from 68.29% to 78.05%,
      whereas the specificity decreased slightly from 91.89% to 86.49%. CoroMarker was
      stable in plasma because it was mainly in the extracellular vesicles (EVs),
      probably from monocytes. We conclude that CoroMarker is a stable, sensitive and
      specific biomarker for CAD. 

PMID- 26201020
TI  - Interaction in endothelium of non-muscular myosin light-chain kinase and the NF
      kappaB pathway is critical to lipopolysaccharide-induced vascular hyporeactivity.
AB  - During sepsis, endothelial barrier dysfunction contributes to cardiovascular
      failure, mainly through the release of oxidative metabolites by penetrant
      leukocytes. We reported the non-muscular isoform of myosin light chain kinase
      (nmMLCK) playing a pivotal role in endotoxin shock injury associated with
      oxidative and nitrative stresses, and vascular hyporeactivity. The present study
      was aimed at understanding the molecular mechanism of lipopolysaccharide (LPS)
      induced vascular alterations as well as studying a probable functional
      association of nmMLCK with nuclear factor kappa-light-chain enhancer of activated
      B cells (NF-kappaB). Aortic rings from mice were exposed in vitro to LPS and,
      then, vascular reactivity was measured. Human aortic endothelial cells (HAoECs)
      were incubated with LPS, and interaction of nmMLCK with NF-kappaB was analysed.
      We provide evidence that nmMLCK deletion prevents vascular hyporeactivity induced
      by in vitro LPS treatment but not endothelial dysfunction in the aorta. Deletion
      of nmMLCK inhibits LPS-induced NF-kappaB activation and increases nitric oxide
      (NO) release via induction of inducible NO synthase (iNOS) within the vascular
      wall. Also, removal of endothelium prevented both NF-kappaB and iNOS expression
      in aortic rings. Among the proinflammatory factors released by LPS-treated
      endothelial cells, interleukin-6 accounts for the induction of iNOS on smooth
      muscle cells in response to LPS. Of particular interest is the demonstration
      that, in HAoECs, LPS-induced NF-kappaB activation occurs via increased MLCK
      activity sensitive to the MLCK inhibitor, ML-7, and physical interactions between
      nmMLCK and NF-kappaB. We report for the first time on NF-kappaB as a novel
      partner of nmMLCK within endothelial cells. The present study demonstrates a
      pivotal role of nmMLCK in vascular inflammatory pathologies. 

PMID- 26201021
TI  - CD147 promotes liver fibrosis progression via VEGF-A/VEGFR2 signalling-mediated
      cross-talk between hepatocytes and sinusoidal endothelial cells.
AB  - Although previous evidence indicates close involvement of CD147 in the
      pathogenesis of liver fibrosis, the underlying molecular mechanisms and its
      therapeutic value remain largely unknown. In the present study, we investigated
      the biological roles of CD147 in liver fibrosis and assessed its therapeutic
      value as a target molecule in the CCl4-induced liver fibrosis mouse model. We
      found that CD147 was highly expressed in both hepatocytes and SECs (sinusoidal
      endothelial cells) in fibrotic liver tissues. Additionally, it was significantly
      associated with the fibrosis stage. TGF-beta1 (transforming growth factor beta1)
      was found to be mainly responsible for the up-regulation of CD147. Bioinformatic
      and experimental data suggest a functional link between CD147 expression and VEGF
      A (vascular endothelial growth factor A)/VEGR-2 (VEGF receptor 2) signalling
      mediated angiogenesis in fibrotic liver tissues. Furthermore, we observed that
      the CD147-induced activation of the PI3K (phosphoinositide 3-kinase)/Akt
      signalling pathway promotes the production of VEGF-A in hepatocytes and
      expression of VEGFR-2 in SECs, which was found to enhance the angiogenic
      capability of SECs. Finally, our data indicate that blocking of CD147 using an
      mAb (monoclonal antibody) attenuated liver fibrosis progression via inhibition of
      VEGF-A/VEGFR-2 signalling and subsequent amelioration of microvascular
      abnormality in the CCl4-induced mouse model. Our findings suggest a novel
      functional mechanism that CD147 may promote liver fibrosis progression via
      inducing the VEGF-A/VEGFR-2 signalling pathway-mediated cross-talk between
      hepatocytes and SECs. New strategies based on the intervention of CD147 can be
      expected for prevention of liver fibrosis. 

PMID- 26201022
TI  - Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis
      of Dupuytren's contracture: a novel target for a possible future therapeutic
      strategy?
AB  - Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand
      causing fibrotic nodules and fascial cords which determine debilitating
      contracture and deformities of fingers and hands. The present study was designed
      to characterize pro-inflammatory cytokines and growth factors involved in the
      pathogenesis, progression and recurrence of this disease, in order to find novel
      targets for alternative therapies and strategies in controlling DC. The
      expression of pro-inflammatory cytokines and of growth factors was detected by
      immunohistochemistry in fibrotic nodules and normal palmar fascia resected
      respectively from patients affected by DC and carpal tunnel syndrome (CTS; as
      negative controls). Reverse transcription (RT)-PCR analysis and
      immunofluorescence were performed to quantify the expression of transforming
      growth factor (TGF)-beta1, interleukin (IL)-1beta and vascular endothelial growth
      factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from
      Dupuytren's nodules. Histological analysis showed high cellularity and high
      proliferation rate in Dupuytren's tissue, together with the presence of
      myofibroblastic isotypes; immunohistochemical staining for macrophages was
      completely negative. In addition, a strong expression of TGF-beta1, IL-1beta and
      VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts
      and myofibroblasts in Dupuytren's nodular tissues, as compared with control
      tissues. These results were confirmed by RT-PCR and by immunofluorescence in
      pathological and normal primary cell cultures. These preliminary observations
      suggest that TGF-beta1, IL-1beta and VEGF may be considered potential therapeutic
      targets in the treatment of Dupuytren's disease (DD). 

PMID- 26201023
TI  - Necroptosis is a key pathogenic event in human and experimental murine models of
      non-alcoholic steatohepatitis.
AB  - Hepatocyte cell death, inflammation and oxidative stress constitute key
      pathogenic mechanisms underlying non-alcoholic fatty liver disease (NAFLD). We
      aimed to investigate the role of necroptosis in human and experimental NAFLD and
      its association with tumour necrosis factor alpha (TNF-alpha) and oxidative
      stress. Serum markers of necrosis, liver receptor-interacting protein 3 (RIP3)
      and phosphorylated mixed lineage kinase domain-like (MLKL) were evaluated in
      control individuals and patients with NAFLD. C57BL/6 wild-type (WT) or RIP3
      deficient (RIP3(-/-)) mice were fed a high-fat choline-deficient (HFCD) or
      methionine and choline-deficient (MCD) diet, with subsequent histological and
      biochemical analysis of hepatic damage. In primary murine hepatocytes,
      necroptosis and oxidative stress were also assessed after necrostatin-1 (Nec-1)
      treatment or RIP3 silencing. We show that circulating markers of necrosis and TNF
      alpha, as well as liver RIP3 and MLKL phosphorylation were increased in NAFLD.
      Likewise, RIP3 and MLKL protein levels and TNF-alpha expression were increased in
      the liver of HFCD and MCD diet-fed mice. Moreover, RIP3 and MLKL sequestration in
      the insoluble protein fraction of NASH (non-alcoholic steatohepatitis) mice liver
      lysates represented an early event during stetatohepatitis progression.
      Functional studies in primary murine hepatocytes established the association
      between TNF-alpha-induced RIP3 expression, activation of necroptosis and
      oxidative stress. Strikingly, RIP3 deficiency attenuated MCD diet-induced liver
      injury, steatosis, inflammation, fibrosis and oxidative stress. In conclusion,
      necroptosis is increased in the liver of NAFLD patients and in experimental
      models of NASH. Further, TNF-alpha triggers RIP3-dependent oxidative stress
      during hepatocyte necroptosis. As such, targeting necroptosis appears to arrest
      or at least impair NAFLD progression. 

PMID- 26201024
TI  - Vascular endothelial growth factor-A165b prevents diabetic neuropathic pain and
      sensory neuronal degeneration.
AB  - Diabetic peripheral neuropathy affects up to half of diabetic patients. This
      neuronal damage leads to sensory disturbances, including allodynia and
      hyperalgesia. Many growth factors have been suggested as useful treatments for
      prevention of neurodegeneration, including the vascular endothelial growth factor
      (VEGF) family. VEGF-A is generated as two alternative splice variant families.
      The most widely studied isoform, VEGF-A165a is both pro-angiogenic and
      neuroprotective, but pro-nociceptive and increases vascular permeability in
      animal models. Streptozotocin (STZ)-induced diabetic rats develop both
      hyperglycaemia and many of the resulting diabetic complications seen in patients,
      including peripheral neuropathy. In the present study, we show that the anti
      angiogenic VEGF-A splice variant, VEGF-A165b, is also a potential therapeutic for
      diabetic neuropathy. Seven weeks of VEGF-A165b treatment in diabetic rats
      reversed enhanced pain behaviour in multiple behavioural paradigms and was
      neuroprotective, reducing hyperglycaemia-induced activated caspase 3 (AC3) levels
      in sensory neuronal subsets, epidermal sensory nerve fibre loss and aberrant
      sciatic nerve morphology. Furthermore, VEGF-A165b inhibited a STZ-induced
      increase in Evans Blue extravasation in dorsal root ganglia (DRG), saphenous
      nerve and plantar skin of the hind paw. Increased transient receptor potential
      ankyrin 1 (TRPA1) channel activity is associated with the onset of diabetic
      neuropathy. VEGF-A165b also prevented hyperglycaemia-enhanced TRPA1 activity in
      an in vitro sensory neuronal cell line indicating a novel direct neuronal
      mechanism that could underlie the anti-nociceptive effect observed in vivo. These
      results demonstrate that in a model of Type I diabetes VEGF-A165b attenuates
      altered pain behaviour and prevents neuronal stress, possibly through an effect
      on TRPA1 activity. 

PMID- 26201025
TI  - Impaired Early-Response Inhibition in Overweight Females with and without Binge
      Eating Disorder.
AB  - OBJECTIVE: Several studies report increased reward sensitivity towards food in
      overweight individuals. By contrast, data is inconclusive with respect to
      response inhibition in overweight individuals without binge eating disorder
      (BED). Hence, the latter was addressed in the present study in a group of
      overweight/obese females with and without BED and a normal-weight control group
      without eating disorders. METHOD: A group of women with BED (n = 29), a group of
      overweight women without BED (n = 33) and normal-weight females (n = 30)
      participated in a pictorial priming paradigm, with food items (relevant primes)
      and office utensils (neutral primes) and color blobs (neutral primes) as stimuli.
      Increased response priming effects (i.e. priming with switches between stimulus
      categories) were taken as indicators of deficient behavioral inhibition. RESULTS:
      Priming effects for neutral primes were moderate and comparable across all
      groups. However, primes associated with the food task set lead to increased
      priming effects in both overweight groups. But, effects were comparable for
      overweight/obese participants with and without BED. DISCUSSION: Results suggest
      that early response inhibition in the context of food is impaired in overweight
      individuals compared to normal-weight individuals.

PMID- 26201026
TI  - Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques.
AB  - Bitter taste receptors (TAS2R proteins) allow mammals to detect and avoid
      ingestion of toxins in food. Thus, TAS2Rs play an important role in food choice
      and are subject to complex natural selection pressures. In our previous study, we
      examined nucleotide variation in TAS2R38, a gene expressing bitter taste receptor
      for phenylthiocarbamide (PTC), in 333 Japanese macaques (Macaca fuscata) from 9
      local populations in Japan. We identified a PTC "non-taster" TAS2R38 allele in
      Japanese macaques that was caused by a loss of the start codon. This PTC non
      taster allele was only found in a limited local population (the Kii area), at a
      frequency of 29%. In this study, we confirmed that this allele was present in
      only the Kii population by analyzing an additional 264 individuals from eight new
      populations. Using cellular and behavioral experiments, we found that this allele
      lost its receptor function for perceiving PTC. The nucleotide sequences of the
      allele including flanking regions (of about 10 kb) from 23 chromosomes were
      identical, suggesting that a non-taster allele arose and expanded in the Kii
      population during the last 13,000 years. Genetic analyses of non-coding regions
      in Kii individuals and neighboring populations indicated that the high allele
      frequency in the Kii population could not be explained by demographic history,
      suggesting that positive selection resulted in a rapid increase in PTC non
      tasters in the Kii population. The loss-of-function that occurred at the TAS2R38
      locus presumably provided a fitness advantage to Japanese macaques in the Kii
      population. Because TAS2R38 ligands are often found in plants, this functional
      change in fitness is perhaps related to feeding habit specificity. These findings
      should provide valuable insights for elucidating adaptive evolutionary changes
      with respect to various environments in wild mammals. 

PMID- 26201027
TI  - Conformational Dynamics of Response Regulator RegX3 from Mycobacterium
      tuberculosis.
AB  - Two-component signal transduction systems (TCS) are vital for adaptive responses
      to various environmental stresses in bacteria, fungi and even plants. A TCS
      typically comprises of a sensor histidine kinase (SK) with its cognate response
      regulator (RR), which often has two domains-N terminal receiver domain (RD) and C
      terminal effector domain (ED). The histidine kinase phosphorylates the RD to
      activate the ED by promoting dimerization. However, despite significant progress
      on structural studies, how RR transmits activation signal from RD to ED remains
      elusive. Here we analyzed active to inactive transition process of OmpR/PhoB
      family using an active conformation of RegX3 from Mycobacterium tuberculosis as a
      model system by computational approaches. An inactive state of RegX3 generated
      from 150 ns molecular dynamic simulation has rotameric conformations of Thr79 and
      Tyr98 that are generally conserved in inactive RRs. Arg81 in loop beta4alpha4
      acts synergistically with loop beta1alpha1 to change its interaction partners
      during active to inactive transition, potentially leading to the N-terminal
      movement of RegX3 helix alpha1. Global conformational dynamics of RegX3 is mainly
      dependent on alpha4beta5 region, in particular seven 'hot-spot' residues (Tyr98
      to Ser104), adjacent to which several coevolved residues at dimeric interface,
      including Ile76-Asp96, Asp97-Arg111 and Glu24-Arg113 pairs, are critical for
      signal transduction. Taken together, our computational analyses suggest a
      molecular linkage between Asp phosphorylation, proximal loops and
      alpha4beta5alpha5 dimeric interface during RR active to inactive state
      transition, which is not often evidently defined from static crystal structures. 

PMID- 26201028
TI  - Lysimachia huangsangensis (Primulaceae), a New Species from Hunan, China.
AB  - A new species, Lysimachia huangsangensis (Primulaceae), from Hunan, China is
      described and illustrated. The new species is closely related to L. carinata
      because of the crested calyx, but differs in the leaf blades that are ovate to
      elliptic and (3-)4.5-9 * 2-3.4 cm, 2-5-flowered racemes, and the calyx lobes that
      are ovate-lanceolate and 5-6 * 3-4 mm. The systematic placement and conservation
      status are also discussed. 

PMID- 26201029
TI  - Staphylococcus aureus Colonization of the Mouse Gastrointestinal Tract Is
      Modulated by Wall Teichoic Acid, Capsule, and Surface Proteins.
AB  - Staphylococcus aureus colonizes the nose, throat, skin, and gastrointestinal (GI)
      tract of humans. GI carriage of S. aureus is difficult to eradicate and has been
      shown to facilitate the transmission of the bacterium among individuals. Although
      staphylococcal colonization of the GI tract is asymptomatic, it increases the
      likelihood of infection, particularly skin and soft tissue infections caused by
      USA300 isolates. We established a mouse model of persistent S. aureus GI
      colonization and characterized the impact of selected surface antigens on
      colonization. In competition experiments, an acapsular mutant colonized better
      than the parental strain Newman, whereas mutants defective in sortase A and
      clumping factor A showed impaired ability to colonize the GI tract. Mutants
      lacking protein A, clumping factor B, poly-N-acetyl glucosamine, or SdrCDE showed
      no defect in colonization. An S. aureus wall teichoic acid (WTA) mutant
      (DeltatagO) failed to colonize the mouse nose or GI tract, and the tagO and clfA
      mutants showed reduced adherence in vitro to intestinal epithelial cells. The
      tagO mutant was recovered in lower numbers than the wild type strain in the
      murine stomach and duodenum 1 h after inoculation. This reduced fitness
      correlated with the in vitro susceptibility of the tagO mutant to bile salts,
      proteases, and a gut-associated defensin. Newman DeltatagO showed enhanced
      susceptibility to autolysis, and an autolysin (atl) tagO double mutant abrogated
      this phenotype. However, the atl tagO mutant did not survive better in the mouse
      GI tract than the tagO mutant. Our results indicate that the failure of the tagO
      mutant to colonize the GI tract correlates with its poor adherence and
      susceptibility to bactericidal factors within the mouse gut, but not to enhanced
      activity of its major autolysin. 

PMID- 26201034
TI  - International Association for Suicide Prevention.

PMID- 26201030
TI  - Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals
      Functional Pathways Related to Psychosis and Autism Spectrum Disorder.
AB  - BACKGROUND: 22q11.2 Deletion Syndrome (22q11DS) represents one of the greatest
      known genetic risk factors for the development of psychotic illness, and is also
      associated with high rates of autistic spectrum disorders (ASD) in childhood. We
      performed integrated genomic analyses of 22q11DS to identify genes and pathways
      related to specific phenotypes. METHODS: We used a high-resolution aCGH array to
      precisely characterize deletion breakpoints. Using peripheral blood, we examined
      differential expression (DE) and networks of co-expressed genes related to
      phenotypic variation within 22q11DS patients. Whole-genome transcriptional
      profiling was performed using Illumina Human HT-12 microarrays. Data mining
      techniques were used to validate our results against independent samples of both
      peripheral blood and brain tissue from idiopathic psychosis and ASD cases.
      RESULTS: Eighty-five percent of 22q11DS individuals (N = 39) carried the typical
      3 Mb deletion, with significant variability in deletion characteristics in the
      remainder of the sample (N = 7). DE analysis and weighted gene co-expression
      network analysis (WGCNA) identified expression changes related to psychotic
      symptoms in patients, including a module of co-expressed genes which was
      associated with psychosis in 22q11DS and involved in pathways associated with
      transcriptional regulation. This module was enriched for brain-expressed genes,
      was not related to antipsychotic medication use, and significantly overlapped
      with transcriptional changes in idiopathic schizophrenia. In 22q11DS-ASD, both DE
      and WGCNA analyses implicated dysregulation of immune response pathways. The ASD
      associated module showed significant overlap with genes previously associated
      with idiopathic ASD. CONCLUSION: These findings further support the use of
      peripheral tissue in the study of major mutational models of diseases affecting
      the brain, and point towards specific pathways dysregulated in 22q11DS carriers
      with psychosis and ASD.

PMID- 26201031
TI  - Salt Reduction Initiatives around the World - A Systematic Review of Progress
      towards the Global Target.
AB  - OBJECTIVE: To quantify progress with the initiation of salt reduction strategies
      around the world in the context of the global target to reduce population salt
      intake by 30% by 2025. METHODS: A systematic review of the published and grey
      literature was supplemented by questionnaires sent to country program leaders.
      Core characteristics of strategies were extracted and categorised according to a
      pre-defined framework. RESULTS: A total of 75 countries now have a national salt
      reduction strategy, more than double the number reported in a similar review done
      in 2010. The majority of programs are multifaceted and include industry
      engagement to reformulate products (n = 61), establishment of sodium content
      targets for foods (39), consumer education (71), front-of-pack labelling schemes
      (31), taxation on high-salt foods (3) and interventions in public institutions
      (54). Legislative action related to salt reduction such as mandatory targets,
      front of pack labelling, food procurement policies and taxation have been
      implemented in 33 countries. 12 countries have reported reductions in population
      salt intake, 19 reduced salt content in foods and 6 improvements in consumer
      knowledge, attitudes or behaviours relating to salt. CONCLUSION: The large and
      increasing number of countries with salt reduction strategies in place is
      encouraging although activity remains limited in low- and middle-income regions.
      The absence of a consistent approach to implementation highlights uncertainty
      about the elements most important to success. Rigorous evaluation of ongoing
      programs and initiation of salt reduction programs, particularly in low- and
      middle- income countries, will be vital to achieving the targeted 30% reduction
      in salt intake.

PMID- 26201035
TI  - Absolute Lymphocyte Count Recovery Independently Predicts Outcome in Childhood
      Acute Lymphoblastic Leukemia: Experience From a Tertiary Care Cancer Center of a
      Developing Country.
AB  - BACKGROUND: Accurate risk stratification is essential for successful treatment
      outcome in childhood acute lymphoblastic leukemia. Early recovery of absolute
      lymphocyte count (ALC) during induction therapy is emerging as a reliable
      favorable prognostic indicator that may hold its relevance in resource-constraint
      settings. MATERIALS AND METHODS: This is a retrospective chart review of medical
      records of 212 patients of acute lymphoblastic leukemia, aged less than 18 years,
      treated between January 1996 and December 2009. Time to lymphocyte recovery was
      analyzed with respect to various prognostic factors and survival and Martingale
      residuals were used to define ALC cut-offs. RESULTS: High-risk disease
      characteristics including older age (10 y and older), National Cancer Institute
      high risk, and central nervous system disease at diagnosis were associated with
      delayed lymphocyte recovery. The 5-year event-free, relapse-free, and overall
      survival of patients with day 15 ALC of >= 500 cells/uL and day 29 ALC of >= 1000
      cells/uL was 81.7% +/- 4%, 86.4% +/- 2.8%, 91.0% +/- 3%, respectively, compared
      with those with delayed recovery (16.6% +/- 5.6%, 19.3% +/- 6.4%, 32.8% +/- 7.2%,
      P < 0.001). In multivariate analysis both these ALC cut-offs retained their
      significance as prognostic variables of survival. CONCLUSION: Our analysis
      revealed ALC to be an important independent predictor of treatment outcome and
      may provide key prognostic information in settings where minimal residual disease
      based risk stratification is not feasible.

PMID- 26201036
TI  - Additional Therapies to Improve Metastatic Response to Induction Therapy in
      Children With High-risk Neuroblastoma.
AB  - Children with high-risk neuroblastoma who fail to achieve adequate metastatic
      response after induction chemotherapy have dismal outcome and new therapeutic
      strategies are needed. However, timing of introduction of novel agents still
      remains under discussion. Given an increase in number of phase I-II studies of
      molecularly targeted drugs in neuroblastoma, it is crucial to determine, as early
      as possible, which patients may be suitable candidates for new therapeutic
      strategies. This single-center retrospective analysis of patients with high-risk
      neuroblastoma showed that the addition of conventional chemotherapy improved the
      quality of metastatic response only for the group of patients with partial
      response. It is therefore proposed to develop stratification criteria for those
      patients very unlikely to benefit from a plethora of additional lines of
      treatment, but might benefit from introduction of novel agents. 

PMID- 26201038
TI  - Partnering with home healthcare agencies to improve care transitions.

PMID- 26201039
TI  - Increasing professional nursing certification.

PMID- 26201040
TI  - Are you an evolutionary leader?

PMID- 26201041
TI  - Clinical competence and EBP: An educator's perspective.

PMID- 26201037
TI  - Guidelines for the Standard Monitoring of Patients With Thalassemia: Report of
      the Thalassemia Longitudinal Cohort.
AB  - Chronic transfusion therapy has played a central role in extending life
      expectancy for patients with hemoglobinopathies such as thalassemia. However,
      this life-saving therapy is associated with numerous complications that now
      comprise the bulk of management considerations for patients with thalassemia.
      This review reports on the experience of the Thalassemia Longitudinal Cohort and
      reviews available literature to establish guidelines for the management of
      patients with thalassemia. 

PMID- 26201043
TI  - Patient care outcomes and temporary nurses.

PMID- 26201044
TI  - AACN CSI Academy, part 2: Nurses emerge as change leaders.
AB  - In the first part of this three-part series, we explored how the American
      Association of Critical-Care Nurses (AACN) Clinical Scene Investigator (CSI)
      Academy aids clinical nurses in cultivating skills that measurably demonstrate
      how nonproductive time is a misnomer that interferes with achieving optimal
      patient outcomes. Join us for part 2, as we examine how the CSI Academy helped
      one hospital's neurosurgical ICU (NSCU) nurses achieve zero CAUTIs. 

PMID- 26201045
TI  - Academic-practice partnerships: A tale of two cultures.

PMID- 26201046
TI  - A look at nurse consultancy.

PMID- 26201047
TI  - Leadership Q&A.

PMID- 26201048
TI  - Simultaneous solvent screening and reaction optimization in microliter slugs.
AB  - An automated, continuous flow droplet screening system is presented, enabling
      real-time simultaneous solvent and continuous variable optimization. An optimal
      design of experiments strategy is applied to the alkylation of 1,2
      diaminocyclohexane in 16 MUL droplets, with scale-up demonstrated. Analysis of
      segmented flow results suggests correlation of yield with solvent hydrogen bond
      basicity. 

PMID- 26201049
TI  - Sn(II) induced concentration dependent dynamic to static excimer conversion of a
      conjugated naphthalene derivative.
AB  - The X-ray structurally characterized naphthalene appended diformyl-p-cresol
      derivative () selectively detects Sn(2+) by both colorimetric and fluorescence
      methods. In the presence of Sn(2+), exhibits a monomer emission at 420 nm along
      with a strong red excimer emission at 582 nm in acetonitrile. The excimer
      formation highly depends on Sn(2+) concentration. The dynamic excimer, observed
      with up to 2.5 equivalents of Sn(2+), gradually converts to a static form above
      2.5 equivalents of Sn(2+). Moreover, in a different solvent media, viz. in
      aqueous methanol, can also detect Al(3+) through the generation of intense green
      fluorescence. The photophysical interactions are rationalized by (1)H NMR, mass
      spectra, steady state and lifetime fluorescence measurements. DFT studies support
      the experimental findings. 

PMID- 26201050
TI  - Identification of Serine Conformers by Matrix-Isolation IR Spectroscopy Aided by
      Near-Infrared Laser-Induced Conformational Change, 2D Correlation Analysis, and
      Quantum Mechanical Anharmonic Computations.
AB  - The conformers of alpha-serine were investigated by matrix-isolation IR
      spectroscopy combined with NIR laser irradiation. This method, aided by 2D
      correlation analysis, enabled unambiguously grouping the spectral lines to
      individual conformers. On the basis of comparison of at least nine experimentally
      observed vibrational transitions of each conformer with empirically scaled (SQM)
      and anharmonic (GVPT2) computed IR spectra, six conformers were identified. In
      addition, the presence of at least one more conformer in Ar matrix was proved,
      and a short-lived conformer with a half-life of (3.7 +/- 0.5) * 10(3) s in N2
      matrix was generated by NIR irradiation. The analysis of the NIR laser-induced
      conversions revealed that the excitation of the stretching overtone of both the
      side chain and the carboxylic OH groups can effectively promote conformational
      changes, but remarkably different paths were observed for the two kinds of
      excitations. 

PMID- 26201051
TI  - Are daily physical activities risk factors for knee osteoarthritis?
AB  - AIM: In spite of many epidemiologic studies, there is still insufficient evidence
      on the effects of daily physical activity on osteoarthritis. The purpose of this
      study was to evaluate the association between squatting, climbing, kneeling,
      lifting and carrying weights and knee osteoarthritis. METHODS: This population
      based case control study was the second stage of the World Health Organization -
      Community Oriented Program for Control of Rheumatic Diseases (WHO-COPCORD), in
      which 263 cases and 263 controls aged 30-70 years were selected from 780 eligible
      cases and 4373 eligible controls identified in the first-stage survey in Tehran.
      Demographic and lifestyle data were obtained from all the participants. The
      selection probability of each case and control and the stabilized weight was
      estimated using the restricted cubic spline models. Multivariable regression
      models by inverse probability weighting were used to minimize the effect of the
      bias resulting from the unequal selection probability. RESULTS: The female sex,
      age, obesity and history of previous severe knee injury maintained their strong
      and significant associations with knee osteoarthritis before and after the
      adjustment. Although walking and squatting were significantly different in the
      case and control groups in the bivariate analysis, after adjustment and weighting
      no such association was found between the disease and squatting, kneeling,
      standing, walking, climbing, carrying and lifting. CONCLUSION: This study did not
      show any significant association between knee osteoarthritis and daily
      occupational and non-occupational activities; nevertheless it does add another
      piece of information to the literature on the complex role of physical activities
      in knee osteoarthritis.

PMID- 26201052
TI  - L-Cysteine/D,L-homocysteine-regulated ileum motility via system L and B degrees
      (,+) transporter: Modification by inhibitors of hydrogen sulfide synthesis and
      dietary treatments.
AB  - Previous studies including ours demonstrated that L-cysteine treatments decreased
      motility in gastrointestinal tissues including the ileum via hydrogen sulfide
      (H2S), which is formed from sulfur-containing amino acids such as L-cysteine and
      L-homocysteine. However, the amino acid transport systems involved in L
      cysteine/L-homocysteine-induced responses have not yet been elucidated in detail;
      therefore, we investigated these systems pharmacologically by measuring
      electrical stimulation (ES)-induced contractions with amino acids in mouse ileum
      preparations. The treatments with L-cysteine and D,L-homocysteine inhibited ES
      induced contractions in ileum preparations from fasted mice, and these responses
      were decreased by the treatment with 2-aminobicyclo[2.2.1]heptane-2-carboxylate
      (BCH), an inhibitor of systems L and B degrees (,+). The results obtained using
      ileum preparations and a model cell line (PC12 cells) with various amino acids
      and BCH showed that not only L-cysteine, but also aminooxyacetic acid and D,L
      propargylglycine, which act as H2S synthesis inhibitors, appeared to be taken up
      by these preparations/cells in L and B degrees (,+) system-dependent manners. The
      L-cysteine and D,L-homocysteine responses were delayed and abolished,
      respectively, in ileum preparations from fed mice. Our results suggested that the
      regulation of ileum motility by L-cysteine and D,L-homocysteine was dependent on
      BCH-sensitive systems, and varied depending on feeding in mice. Therefore, the
      effects of aminooxyacetic acid and D,L-propargylglycine on transport systems need
      to be considered in pharmacological analyses.

PMID- 26201053
TI  - Allelic Spectra of Risk SNPs Are Different for Environment/Lifestyle Dependent
      versus Independent Diseases.
AB  - Genome-wide association studies (GWAS) have generated sufficient data to assess
      the role of selection in shaping allelic diversity of disease-associated SNPs.
      Negative selection against disease risk variants is expected to reduce their
      frequencies making them overrepresented in the group of minor (<50%) alleles.
      Indeed, we found that the overall proportion of risk alleles was higher among
      alleles with frequency <50% (minor alleles) compared to that in the group of
      major alleles. We hypothesized that negative selection may have different effects
      on environment (or lifestyle)-dependent versus environment (or lifestyle)
      independent diseases. We used an environment/lifestyle index (ELI) to assess
      influence of environmental/lifestyle factors on disease etiology. ELI was defined
      as the number of publications mentioning "environment" or "lifestyle" AND disease
      per 1,000 disease-mentioning publications. We found that the frequency
      distributions of the risk alleles for the diseases with strong
      environmental/lifestyle components follow the distribution expected under a
      selectively neutral model, while frequency distributions of the risk alleles for
      the diseases with weak environmental/lifestyle influences is shifted to the lower
      values indicating effects of negative selection. We hypothesized that previously
      selectively neutral variants become risk alleles when environment changes. The
      hypothesis of ancestrally neutral, currently disadvantageous risk-associated
      alleles predicts that the distribution of risk alleles for the
      environment/lifestyle dependent diseases will follow a neutral model since
      natural selection has not had enough time to influence allele frequencies. The
      results of our analysis suggest that prediction of SNP functionality based on the
      level of evolutionary conservation may not be useful for SNPs associated with
      environment/lifestyle dependent diseases. 

PMID- 26201054
TI  - Course of Posttraumatic Stress Disorder 40 Years After the Vietnam War: Findings
      From the National Vietnam Veterans Longitudinal Study.
AB  - IMPORTANCE: The long-term course of readjustment problems in military personnel
      has not been evaluated in a nationally representative sample. The National
      Vietnam Veterans Longitudinal Study (NVVLS) is a congressionally mandated
      assessment of Vietnam veterans who underwent previous assessment in the National
      Vietnam Veterans Readjustment Study (NVVRS). OBJECTIVE: To determine the
      prevalence, course, and comorbidities of war-zone posttraumatic stress disorder
      (PTSD) across a 25-year interval. DESIGN, SETTING, AND PARTICIPANTS: The NVVLS
      survey consisted of a self-report health questionnaire (n = 1409), a computer
      assisted telephone survey health interview (n = 1279), and a telephone clinical
      interview (n = 400) in a representative national sample of veterans who served in
      the Vietnam theater of operations (theater veterans) from July 3, 2012, through
      May 17, 2013. Of 2348 NVVRS participants, 1920 were alive at the outset of the
      NVVLS, and 81 died during recruitment; 1450 of the remaining 1839 (78.8%)
      participated in at least 1 NVVLS study phase. Data analysis was performed from
      May 18, 2013, through January 9, 2015, with further analyses continued through
      April 13, 2015. MAIN OUTCOMES AND MEASURES: Study instruments included the
      Mississippi Scale for Combat-Related PTSD, PTSD Checklist for DSM-IV supplemented
      with PTSD Checklist for DSM-5 items (PCL-5+), Clinician-Administered PTSD Scale
      for DSM-5 (CAPS-5), and Structured Clinical Interview for DSM-IV, Nonpatient
      Version. RESULTS: Among male theater veterans, we estimated a prevalence (95% CI)
      of 4.5% (1.7%-7.3%) based on CAPS-5 criteria for a current PTSD diagnosis; 10.8%
      (6.5%-15.1%) based on CAPS-5 full plus subthreshold PTSD; and 11.2% (8.3%-14.2%)
      based on PCL-5+ criteria for current war-zone PTSD. Among female veterans,
      estimates were 6.1% (1.8%-10.3%), 8.7% (3.8%-13.6%), and 6.6% (3.5%-9.6%),
      respectively. The PCL-5+ prevalence (95% CI) of current non-war-zone PTSD was
      4.6% (2.6%-6.6%) in male and 5.1% (2.3%-8.0%) in female theater veterans.
      Comorbid major depression occurred in 36.7% (95% CI, 6.2%-67.2%) of veterans with
      current war-zone PTSD. With regard to the course of PTSD, 16.0% of theater
      veterans reported an increase and 7.6% reported a decrease of greater than 20
      points in Mississippi Scale for Combat-Related PTSD symptoms. The prevalence (95%
      CI) of current PCL-5+-derived PTSD in study respondents was 1.2% (0.0%-3.0%) for
      male and 3.9% (0.0%-8.1%) for female Vietnam veterans. CONCLUSIONS AND RELEVANCE:
      Approximately 271,000 Vietnam theater veterans have current full PTSD plus
      subthreshold war-zone PTSD, one-third of whom have current major depressive
      disorder, 40 or more years after the war. These findings underscore the need for
      mental health services for many decades for veterans with PTSD symptoms.

PMID- 26201055
TI  - Extract from Ceratonia siliqua Exhibits Depigmentation Properties.
AB  - Skin hyper-pigmentation is a condition initiated by the overproduction of melanin
      existing in the melanocytes. Melanin pigment is responsible for the colour of
      skin in humans. It is formed through a series of oxidative reactions involving
      the amino acid tyrosine in the presence of the key enzyme tyrosinase. In
      continuation with our efforts to identify tyrosinase inhibitors from plants
      sources, the methanol extract from leaf, bark and fruit of Ceratonia siliqua were
      screened for tyrosinase inhibition and diphenolase activity. The bark extract
      exhibited significant inhibition on mushroom tyrosinase using L-tyrosine as a
      substrate and showed diphenolase activity. The extract further significantly
      lowered tyrosinase mRNA levels in B16-F10 mouse melanocytes. Bioassay-guided
      fractionation led to the isolation of six compounds. Compounds (-)-epicatechin-3
      O-gallate, 1,2,3,6-tetra-O-galloyl-beta-D-glucose and gallocatechin-3-O-gallate
      showed tyrosinase inhibitions with the IC50 values of 27.52, 83.30 and 28.30
      ug/mL, respectively. These compounds also exhibited L-DOPA activities with IC50
      values of >200, 150 and 200 ug/mL, respectively. A clinical study was conducted
      using 20 volunteers in a patch testing trial for irritancy potential and skin
      depigmentation. The clinical results showed the sample to be non-irritant with
      irritancy potential of -34.21 and depigmentation trial showed an improvement in
      the even skin tone of UV induced pigmentation at 3% after 28 days of application.

PMID- 26201056
TI  - Transition from identity to bioactivity-guided proteomics for biomarker discovery
      with focus on the PF2D platform.
AB  - Proteomic strategies provide a valuable tool kit to identify proteins involved in
      diseases. With recent progress in MS technology, high throughput proteomics has
      accelerated protein identification for potential biomarkers. Numerous biomarker
      candidates have been identified in several diseases, and many are common among
      pathologies. An overall strategy that could complement and strengthen the search
      for biomarkers is combining protein identity with biological outcomes. This
      review describes an emerging framework of bridging bioactivity to protein
      identity, exploring the possibility that some biomarkers will have a mechanistic
      role in the disease process. A review of pulmonary, cardiovascular, and CNS
      biomarkers will be discussed to demonstrate the utility of combining bioactivity
      with identification as a means to not only find meaningful biomarkers, but also
      to uncover functional mediators of disease. 

PMID- 26201057
TI  - Cytochrome P450 induction response in tethered spheroids as a three-dimensional
      human hepatocyte in vitro model.
AB  - Cytochrome P450 (CYP) induction is a key risk factor of clinical drug-drug
      interactions that has to be mitigated in the early phases of drug discovery.
      Three-dimensional (3D) cultures of hepatocytes in vitro have recently emerged as
      a potentially better platform to recapitulate the in vivo liver structure and to
      maintain long-term hepatic functions as compared with conventional two
      dimensional (2D) monolayer cultures. However, the majority of published studies
      on 3D hepatocyte models use rat hepatocytes and the response to CYP inducers
      between rodents and humans is distinct. In the present study, we constructed
      tethered spheroids on RGD/galactose-conjugated membranes as an in vitro 3D model
      using cryopreserved human hepatocytes. CYP3A4 mRNA expression in the tethered
      spheroids was induced to a significantly greater extent than those in the
      collagen sandwich cultures, indicating the transcriptional regulation was more
      sensitive to the CYP inducers in the 3D model. Induction of CYP1A2, CYP2B6 and
      CYP3A4 activities in the tethered spheroids were comparable to, if not higher
      than that observed in the collagen sandwich cultures. The membrane-based model is
      readily integrated into multi-well plates for higher-throughput drug testing
      applications, which might be an alternative model to screen the CYP induction
      potential in vitro with more physiological relevance.

PMID- 26201058
TI  - Aggravating effect of atorvastatin on indomethacin-induced gastric injury: Focus
      on PGE2, TNF-alpha, neutrophils and iNOS.
AB  - Statins are suggested to possess healing properties due to their antioxidant and
      antiinflammatory effects in animal ulcer models. In contrary, a clinical report
      indicated the formation of gastric ulcer by the use of atorvastatin. In this
      study, we aimed to investigate the effects of atorvastatin (0.5, 5 and 50mg/kg,
      p.o.) after single (acute) and multiple (subchronic, 5 days) applications on
      indomethacin-induced gastric ulcer in rats. In both acute and subchronic models
      high dose atorvastatin (50mg/kg), unlike to lower doses (0,5 and 5mg/kg),
      significantly aggravated ulcer lesions induced by indomethacin (30 mg/kg)
      although, a direct ulcerogenic influence was lacking. Proulcerogenic effect of
      atorvastatin are likely to be associated with decreased mucosal defense
      mechanisms (GSH and PGE2), and increased neutrophil infiltration and
      proinflammatory factors (TNF-a and iNOS) possibly via independently from
      mevalonate pathway. Thus, atorvastatin therapy should be monitorized in patients
      for an increased risk of gastric ulcer particularly when used concomitantly with
      NSAIDs.

PMID- 26201059
TI  - Aspirin and lipid mediators in the cardiovascular system.
AB  - Aspirin is an unique compound because it bears two active moieties within one and
      the same molecule: a reactive acetyl group and the salicylate metabolite.
      Salicylate has some effects similar to aspirin, however only at higher
      concentrations, usually in the millimolar range, which are not obtained at
      conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological
      actions of aspirin in the cardiovascular system at these doses are largely if not
      entirely due to target structure acetylation. Several classes of lipid mediators
      become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with
      subsequent inhibition of thromboxane and, possibly, thrombin formation. By this
      action, aspirin also inhibits paracrine thromboxane functions on other lipid
      mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an
      inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE
      and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with
      white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates
      eNOS with subsequent upregulation of NO formation and enhanced expression of the
      antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated.
      Many more acetylation targets have been identified in live cells by quantitative
      acid-cleavable activity-based protein profiling and might result in discovery of
      even more aspirin targets in the near future.

PMID- 26201060
TI  - The role of mTOR during cisplatin treatment in an in vitro and ex vivo model of
      cervical cancer.
AB  - Cisplatin is used as a cytotoxic agent for the management of cervical cancer.
      However, the severity of the side-effects limits the use of this drug,
      particularly at high doses. Resistance to cisplatin is often attributed to a
      disruption in the normal apoptotic response via aberrant activation of pathways
      such as the mTOR pathway. Here we assess the role of mTOR and its effect on cell
      death sensitization and autophagy in response to a low concentration of cisplatin
      in cervical cancer cells. Additionally we measured the expression profile of mTOR
      in normal, low- and high-grade squamous intraepithelial (LSIL and HSIL) lesions
      and cancerous tissue. An in vitro model of cervical cancer was established using
      HeLa and CaSki cells. mTOR protein expression as well as autophagy-related
      proteins were evaluated through Western blotting. Inhibition of mTOR was achieved
      with the use of rapamycin and RNA silencing. A low concentration of cisplatin
      administered as a single agent induces autophagy, but not apoptosis. Cisplatin
      cytotoxicity was greatly enhanced in cancer cells when mTOR had been inhibited
      prior to cisplatin treatment which was likely due to autophagy being increased
      above cisplatin-induced levels, thereby inducing apoptosis. Cervical tissue
      samples revealed an increase in mTOR protein expression in LSIL and carcinoma
      tissue which suggests a change in autophagy control. Our data suggest that
      utilising a lower dose of cisplatin combined with mTOR inhibition is a viable
      treatment option and addresses the challenge of cisplatin dose-dependent
      toxicity, however future studies are required to confirm this in a clinical
      setting. 

PMID- 26201061
TI  - In vitro structure-toxicity relationship of chalcones in human hepatic stellate
      cells.
AB  - Xanthohumol (XN), the major prenylated chalcone from hops (Humulus lupulus L.),
      has received much attention within the last years, due to its multiple
      pharmacological activities including anti-proliferative, anti-inflammatory,
      antioxidant, pro-apoptotic, anti-bacterial and anti-adhesive effects. However,
      there exists a huge number of metabolites and structurally-related chalcones,
      which can be expected, or are already known, to exhibit various effects on cells.
      We have therefore analyzed the effects of XN and 18 other chalcones in a panel,
      consisting of multiple cell-based assays. Readouts of these assays addressed
      distinct aspects of cell-toxicity, like proliferation, mitochondrial health, cell
      cycle and other cellular features. Besides known active structural elements of
      chalcones, like the Michael system, we have identified several moieties that seem
      to have an impact on specific effects and toxicity in human liver cells in vitro.
      Based on these observations, we present a structure-toxicity model, which will be
      crucial to understand the molecular mechanisms of wanted effects and unwanted
      side-effects of chalcones. 

PMID- 26201062
TI  - A new therapeutic approach for carbon monoxide poisoning: Antioxidants.

PMID- 26201064
TI  - Roofing Materials Assessment: Investigation of 1 Five Metals in Runoff from
      Roofing Materials.

PMID- 26201065
TI  - TMA Uncovers Medicare Mistakes.
AB  - The Texas Medical Association recently uncovered some major Medicare mistakes
      that show just why some physicians talk about leaving the federal program.
      Investigations and advocacy by TMA staff put Medicare on the path to a fix. 

PMID- 26201066
TI  - Living the Dream of Private Practice.
AB  - When starting a private practice, physicians often face numerous legal, staffing,
      and real estate hurdles. Many turn to TMA Practice Consulting for help. 

PMID- 26201067
TI  - Choosing Fellowship.
AB  - Fellows tend to practice where they train, making retention critical to an
      adequate physician workforce. But as subspecialties grow, some question whether
      the trend is narrowing access to much-needed general care. 

PMID- 26201068
TI  - Following the Science.
AB  - A bill requiring student athletes to have an EKG before their first and third
      years of participation in school athletics didn't pass this legislative session.
      TMA and other organizations say the scientific evidence doesn't support mass
      screening.

PMID- 26201069
TI  - Documenting Patient Care in EHRs.
AB  - New Texas Medical Board rules attempt to underscore the importance of accurate
      information in the data-saturated electronic health record system and make
      doctors' reporting requirements clearer.

PMID- 26201070
TI  - Technical Assistance Required.
AB  - Medicare's Quality and Resource Use Reports help doctors gauge their performance
      in federal quality reporting mandates. But unraveling the mystery of scattergrams
      and composite scores is not easy.

PMID- 26201071
TI  - Parascolymia (Scleractinia: Lobophylliidae) in the Central Paratethys Sea (Vienna
      Basin, Austria) and its possible biogeographic implications.
AB  - Palaeobiogeographical and palaeodiversity patterns of scleractinian reef corals
      are generally biased due to uncertain taxonomy and a loss of taxonomic characters
      through dissolution and recrystallization of the skeletal aragonite in shallow
      marine limestones. Herein, we describe a fossil lobophylliid coral in mouldic
      preservation from the early middle Miocene Leitha Limestone of the Central
      Paratethys Sea (Vienna Basin, Austria). By using grey-scale image inversion and
      silicone rubber casts for the visualization of the original skeletal anatomy and
      the detection of distinct micromorphological characters (i.e. shape of septal
      teeth, granulation of septocostae) Parascolymia bracherti has been identified as
      a new species in spite of the dissolved skeleton. In the recent era, Parascolymia
      like all Lobophylliidae is restricted to the Indo-Pacific region, where it is
      represented by a single species. The new species proves the genus also in the
      Miocene Mediterranean reef coral province. A review of the spatio-temporal
      relationships of fossil corals related to Parascolymia indicates that the genus
      was probably rooted in the Eastern Atlantic-Western Tethys region during the
      Paleocene to Eocene and reached the Indo-Pacific region not before the Oligocene.
      The revealed palaeobiogeographical pattern shows an obvious congruence with that
      of Acropora and tridacnine bivalves reflecting a gradual equatorwards retreat of
      the marine biodiversity center parallel to the Cenozoic climate deterioration. 

PMID- 26201072
TI  - The Role of High Mobility Group Box 1 Protein (HMGB1) in the Immunopathology of
      Experimental Pulmonary Tuberculosis.
AB  - BACKGROUND: The high mobility group box 1 (HMGB1) is the prototype of alarmin
      protein released by stressed or dying cells. The redox state of this protein
      confers different functions in the regulation of inflammation and immune
      response. AIM: Determine the kinetics, cellular sources and function of HMGB1 in
      experimental tuberculosis. METHODS: BALB/c mice were infected with Mycobacterium
      tuberculosis strain H37Rv. At different time points, HMGB1 was quantified in
      bronchial lavage fluid (BALF) and in lungs was determined its cellular sources by
      immunohistochemistry. HMGB1 was blocked with specific antibodies or recombinant
      HMGB1 was administered during early or late infection. Bacilli burdens,
      inflammation and cytokines expression were determined. RESULTS: The maximal
      concentration of HMGB1 in BALF was at day one of infection. Bronchial epithelium
      and macrophages were the most important sources. At day 7 to 21 the oxidized
      HMGB1 was predominant, while during late infection only the reduced form was
      seen. Blocking HMGB1 during early infection produced significant decrease of
      bacilli burdens and high production of pro-inflammatory cytokines, while the
      opposite was seen when HMGB1 was administered. Blocking HMGB1 activity or
      administrated it in high amounts during late infection worsening the disease.
      CONCLUSIONS: HMGB1 is liberated during experimental tuberculosis and promotes or
      suppress the immune response and inflammation depending on the redox state.

PMID- 26201073
TI  - Heat Transfer Modeling of an Annular On-Line Spray Water Cooling Process for
      Electric-Resistance-Welded Steel Pipe.
AB  - On-line spray water cooling (OSWC) of electric-resistance-welded (ERW) steel
      pipes can replace the conventional off-line heat treatment process and become an
      important and critical procedure. The OSWC process improves production
      efficiency, decreases costs, and enhances the mechanical properties of ERW steel
      pipe, especially the impact properties of the weld joint. In this paper, an
      annular OSWC process is investigated based on an experimental simulation platform
      that can obtain precise real-time measurements of the temperature of the pipe,
      the water pressure and flux, etc. The effects of the modes of annular spray water
      cooling and related cooling parameters on the mechanical properties of the pipe
      are investigated. The temperature evolutions of the inner and outer walls of the
      pipe are measured during the spray water cooling process, and the uniformity of
      mechanical properties along the circumferential and longitudinal directions is
      investigated. A heat transfer coefficient model of spray water cooling is
      developed based on measured temperature data in conjunction with simulation using
      the finite element method. Industrial tests prove the validity of the heat
      transfer model of a steel pipe undergoing spray water cooling. The research
      results can provide a basis for the industrial application of the OSWC process in
      the production of ERW steel pipes. 

PMID- 26201074
TI  - Predictive Studies Suggest that the Risk for the Selection of Antibiotic
      Resistance by Biocides Is Likely Low in Stenotrophomonas maltophilia.
AB  - Biocides are used without restriction for several purposes. As a consequence,
      large amounts of biocides are released without any control in the environment, a
      situation that can challenge the microbial population dynamics, including
      selection of antibiotic resistant bacteria. Previous work has shown that
      triclosan selects Stenotrophomonas maltophilia antibiotic resistant mutants
      overexpressing the efflux pump SmeDEF and induces expression of this pump
      triggering transient low-level resistance. In the present work we analyze if two
      other common biocides, benzalkonium chloride and hexachlorophene, trigger
      antibiotic resistance in S. maltophilia. Bioinformatic and biochemical methods
      showed that benzalkonium chloride and hexachlorophene bind the repressor of
      smeDEF, SmeT. Only benzalkonium chloride triggers expression of smeD and its
      effect in transient antibiotic resistance is minor. None of the hexachlorophene
      selected mutants was antibiotic resistant. Two benzalkonium chloride resistant
      mutants presented reduced susceptibility to antibiotics and were impaired in
      growth. Metabolic profiling showed they were more proficient than their parental
      strain in the use of some dipeptides. We can then conclude that although
      bioinformatic predictions and biochemical studies suggest that both
      hexachlorophene and benzalkonium chloride should induce smeDEF expression leading
      to transient S. maltophilia resistance to antibiotics, phenotypic assays showed
      this not to be true. The facts that hexachlorophene resistant mutants are not
      antibiotic resistant and that the benzalkonium chloride resistant mutants
      presenting altered susceptibility to antibiotics were impaired in growth suggests
      that the risk for the selection (and fixation) of S. maltophilia antibiotic
      resistant mutants by these biocides is likely low, at least in the absence of
      constant selection pressure. 

PMID- 26201075
TI  - Spatially Explicit Modeling Reveals Cephalopod Distributions Match Contrasting
      Trophic Pathways in the Western Mediterranean Sea.
AB  - Populations of the same species can experience different responses to the
      environment throughout their distributional range as a result of spatial and
      temporal heterogeneity in habitat conditions. This highlights the importance of
      understanding the processes governing species distribution at local scales.
      However, research on species distribution often averages environmental covariates
      across large geographic areas, missing variability in population-environment
      interactions within geographically distinct regions. We used spatially explicit
      models to identify interactions between species and environmental, including
      chlorophyll a (Chla) and sea surface temperature (SST), and trophic (prey
      density) conditions, along with processes governing the distribution of two
      cephalopods with contrasting life-histories (octopus and squid) across the
      western Mediterranean Sea. This approach is relevant for cephalopods, since their
      population dynamics are especially sensitive to variations in habitat conditions
      and rarely stable in abundance and location. The regional distributions of the
      two cephalopod species matched two different trophic pathways present in the
      western Mediterranean Sea, associated with the Gulf of Lion upwelling and the
      Ebro river discharges respectively. The effects of the studied environmental and
      trophic conditions were spatially variant in both species, with usually stronger
      effects along their distributional boundaries. We identify areas where prey
      availability limited the abundance of cephalopod populations as well as
      contrasting effects of temperature in the warmest regions. Despite distributional
      patterns matching productive areas, a general negative effect of Chla on
      cephalopod densities suggests that competition pressure is common in the study
      area. Additionally, results highlight the importance of trophic interactions,
      beyond other common environmental factors, in shaping the distribution of
      cephalopod populations. Our study presents a valuable approach for understanding
      the spatially variant ecology of cephalopod populations, which is important for
      fisheries and ecosystem management. 

PMID- 26201076
TI  - Identification of Haptic Based Guiding Using Hard Reins.
AB  - This paper presents identifications of human-human interaction in which one
      person with limited auditory and visual perception of the environment (a
      follower) is guided by an agent with full perceptual capabilities (a guider) via
      a hard rein along a given path. We investigate several identifications of the
      interaction between the guider and the follower such as computational models that
      map states of the follower to actions of the guider and the computational basis
      of the guider to modulate the force on the rein in response to the trust level of
      the follower. Based on experimental identification systems on human
      demonstrations show that the guider and the follower experience learning for an
      optimal stable state-dependent novel 3rd and 2nd order auto-regressive predictive
      and reactive control policies respectively. By modeling the follower's dynamics
      using a time varying virtual damped inertial system, we found that the
      coefficient of virtual damping is most appropriate to explain the trust level of
      the follower at any given time. Moreover, we present the stability of the
      extracted guiding policy when it was implemented on a planar 1-DoF robotic arm.
      Our findings provide a theoretical basis to design advanced human-robot
      interaction algorithms applicable to a variety of situations where a human
      requires the assistance of a robot to perceive the environment. 

PMID- 26201077
TI  - Chromosome Missegregation Associated with RUVBL1 Deficiency.
AB  - RUVBL1 (RuvB-like1) and RUVBL2 (RuvB-like 2) are integral components of
      multisubunit protein complexes involved in processes ranging from cellular
      metabolism, transcription and chromatin remodeling to DNA repair. Here, we show
      that although RUVBL1 and RUVBL2 are known to form heterodimeric complexes in
      which they stabilize each other, the subunits separate during cytokinesis. In
      anaphase-to-telophase transition, RUVBL1 localizes to structures of the mitotic
      spindle apparatus, where it partially co-localizes with polo-like kinase 1
      (PLK1). The ability of PLK1 to phosphorylate RUVBL1-but not RUVBL2-in vitro and
      their physical association in vivo suggest that this kinase differentially
      regulates the function of the RuvB-like proteins during mitosis. We further show
      that siRNA-mediated knock-down of RuvB-like proteins causes severe defects in
      chromosome alignment and segregation. In addition, we show that the ATPase
      activity of RUVBL1 is indispensable for cell proliferation. Our data thus
      demonstrate that RUVBL1 is essential for efficient mitosis and proliferation. 

PMID- 26201078
TI  - On the Distribution of Salient Objects in Web Images and Its Influence on Salient
      Object Detection.
AB  - In recent years it has become apparent that a Gaussian center bias can serve as
      an important prior for visual saliency detection, which has been demonstrated for
      predicting human eye fixations and salient object detection. Tseng et al. have
      shown that the photographer's tendency to place interesting objects in the center
      is a likely cause for the center bias of eye fixations. We investigate the
      influence of the photographer's center bias on salient object detection,
      extending our previous work. We show that the centroid locations of salient
      objects in photographs of Achanta and Liu's data set in fact correlate strongly
      with a Gaussian model. This is an important insight, because it provides an
      empirical motivation and justification for the integration of such a center bias
      in salient object detection algorithms and helps to understand why Gaussian
      models are so effective. To assess the influence of the center bias on salient
      object detection, we integrate an explicit Gaussian center bias model into two
      state-of-the-art salient object detection algorithms. This way, first, we
      quantify the influence of the Gaussian center bias on pixel- and segment-based
      salient object detection. Second, we improve the performance in terms of F1
      score, Fbeta score, area under the recall-precision curve, area under the
      receiver operating characteristic curve, and hit-rate on the well-known data set
      by Achanta and Liu. Third, by debiasing Cheng et al.'s region contrast model, we
      exemplarily demonstrate that implicit center biases are partially responsible for
      the outstanding performance of state-of-the-art algorithms. Last but not least,
      we introduce a non-biased salient object detection method, which is of interest
      for applications in which the image data is not likely to have a photographer's
      center bias (e.g., image data of surveillance cameras or autonomous robots). 

PMID- 26201079
TI  - New ionic liquids based on the complexation of dipropyl sulfide and AlCl3 for
      electrodeposition of aluminum.
AB  - A new kind of ionic liquid based on the complexation of dipropyl sulfide (DPS)
      and AlCl3 has been prepared. The equivalent concentration of AlCl3 in the ionic
      liquid is as high as 2.3 M. More importantly, it is highly fluidic and exhibits
      an ambient ionic conductivity of 1.25 * 10(-4) S cm(-1). This new ionic liquid
      can be successfully used as an electrolyte for electrodeposition of aluminum. 

PMID- 26201080
TI  - The DNA-Binding Domain of S. pombe Mrc1 (Claspin) Acts to Enhance Stalling at
      Replication Barriers.
AB  - During S-phase replication forks can stall at specific genetic loci. At some
      loci, the stalling events depend on the replisome components Schizosaccharomyces
      pombe Swi1 (Saccharomyces cerevisiae Tof1) and Swi3 (S. cerevisiae Csm3) as well
      as factors that bind DNA in a site-specific manner. Using a new genetic screen we
      identified Mrc1 (S. cerevisiae Mrc1/metazoan Claspin) as a replisome component
      involved in replication stalling. Mrc1 is known to form a sub-complex with Swi1
      and Swi3 within the replisome and is required for the intra-S phase checkpoint
      activation. This discovery is surprising as several studies show that S.
      cerevisiae Mrc1 is not required for replication barrier activity. In contrast, we
      show that deletion of S. pombe mrc1 leads to an approximately three-fold
      reduction in barrier activity at several barriers and that Mrc1's role in
      replication fork stalling is independent of its role in checkpoint activation.
      Instead, S. pombe Mrc1 mediated fork stalling requires the presence of a
      functional copy of its phylogenetically conserved DNA binding domain.
      Interestingly, this domain is on the sequence level absent from S. cerevisiae
      Mrc1. Our study indicates that direct interactions between the eukaryotic
      replisome and the DNA are important for site-specific replication stalling. 

PMID- 26201081
TI  - Apolipoprotein E promotes lipid accumulation and differentiation in human
      adipocytes.
AB  - Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid
      accumulation and adipogenic differentiation in adipose tissue. However, little is
      yet known if APOE functions in a similar manner in human adipocytes. This
      prompted us to compare lipid loading and expression of adipocyte differentiation
      markers in APOE-deficient and control adipocytes using the differentiated human
      mesenchymal stem cell line hMSC-Tert as well as primary human and mouse
      adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with
      or without siRNA targeting APOE while murine adipocytes were isolated from wild
      type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes
      accumulated markedly less triglycerides compared to control cells. This
      correlated with strongly decreased gene expression levels of adipocyte markers
      such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as
      the key transcription factor driving adipocyte differentiation, peroxisome
      proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform.
      Similarly, differentiation of murine Apoe-deficient adipocytes was characterized
      by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation
      of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3
      overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL)
      partially restored triglyceride accumulation, but were unable to induce adipocyte
      differentiation, as judged by expression of adipocyte markers. Taken together,
      depletion of endogenous APOE in human adipocytes severely impairs lipid
      accumulation, which is associated with an inability to initiate differentiation.

PMID- 26201082
TI  - The Rho-mDia1 signaling pathway is required for cyclic strain-induced
      cytoskeletal rearrangement of human periodontal ligament cells.
AB  - Tooth movement is the result of periodontal tissue reconstruction. The
      biomechanical effects produced by orthopedic forces can affect the cytoskeletal
      rearrangement of human periodontal ligament cells (hPDLCs). However, the
      mechanisms responsible for the cytoskeletal rearrangement are not completely
      understood. To analyze the effect, we investigated the role of the Rho-mDia1
      signaling pathway in cyclic strain-induced cytoskeletal rearrangement of hPDLCs
      in detail. We cultured hPDLCs on collagen I-coated six-well Bioflex plates and
      then exposed them to cyclic strain with physiological loading (10%) at a
      frequency of 0.1Hz for 6 or 24h using a Flexercell Tension Plus system. Notably,
      the cells cultured on the Bioflex plates showed increased expression levels of
      RhoA-GTP, profilin-1 protein, and the combination of RhoA and mDia1, whereas the
      expression levels of Rho-GDIa were reduced compared with a static control group.
      Furthermore, the cytoskeletal rearrangement of cells was enhanced. However,
      profilin-1 protein expression and cytoskeletal reorganization under cyclic strain
      can decrease due to the overexpression of Rho-GDIa or mDia1-siRNA transfection,
      whereas Rho-GDIa siRNA transfection has the opposite effect on hPDLCs. Together,
      our results demonstrate that the Rho-mDia1 signaling pathway is involved in the
      cytoskeletal rearrangement of hPDLCs induced by cyclic strain. These observations
      may enable a more in-depth understanding of orthodontic tooth movement and the
      reconstruction of PDL and alveolar bone.

PMID- 26201083
TI  - Expressed Emotion, Family Functioning, and Treatment Outcome for Adolescents with
      Anorexia Nervosa.
AB  - The current study examined the relation between parental expressed emotion (EE)
      and treatment outcome among adolescents participating in a treatment study for
      adolescent anorexia nervosa, as well as its impact on family functioning. One
      hundred and twenty-one families were assigned to family-based treatment or
      adolescent-focused therapy. Paternal criticism predicted lesser improvement in
      eating disorder psychopathology at end of treatment. There was also a significant
      interaction between maternal hostility and treatment, indicating that adolescents
      whose mothers displayed hostility had greater increases in percent of expected
      body weight in adolescent-focused therapy than family-based treatment. In
      addition, maternal hostility predicted less improvement in general family
      functioning and family communication at the end of treatment. Findings suggest
      that maternal and paternal EE may differentially impact treatment outcome and
      should be directly attended to in clinical settings. Future research is needed to
      further explore ways in which parental EE can be effectively modified in
      treatment.

PMID- 26201084
TI  - Exploration of Dimethylzinc-Mediated Radical Reactions.
AB  - In this account, our studies on radical reactions that are promoted by
      dimethylzinc and air are described. Advantages of this reagent and differences
      from conventional radical initiators, such as triethylborane, are discussed. 

PMID- 26201086
TI  - On the state of scientific English and how to improve it - part 9: commas re
      visited: Small, but very powerful....

PMID- 26201085
TI  - Remodeling of plasma lipoproteins in patients with rheumatoid arthritis:
      Interleukin-6 receptor-alpha inhibition with tocilizumab.
AB  - PURPOSE: Rheumatoid arthritis (RA) is associated with increased cardiovascular
      risk, mediated in part by elevated circulating interleukin-6 levels and
      proinflammatory changes in plasma lipoproteins. We hypothesized that RA patients
      acquire inflammation-induced modifications to the protein cargo of circulating
      lipoproteins that may be reversed by tocilizumab, an interleukin-6 receptor-alpha
      inhibitor. EXPERIMENTAL DESIGN: Size-exclusion chromatography and reverse-phase
      protein arrays using 29 antibodies against 26 proteins were applied at baseline
      and after tocilizumab treatment to analyze the distributions of apolipoproteins,
      enzymes, lipid transfer proteins, and other associated proteins in plasma
      lipoprotein fractions from 20 women with RA. RESULTS: A 30% reduction in high
      density lipoprotein (HDL)-associated serum amyloid A4 and complement C4 occurred
      with tocilizumab. Levels of C-reactive protein, associated or comigrating with
      HDL and low-density lipoprotein (LDL) peaks, were reduced on treatment by
      approximately 80% and 24%, respectively. Reductions in lipoprotein-associated
      phospholipase A2, lipoprotein (a), and cholesteryl ester transfer protein in the
      LDL fraction suggest reductions in LDL-associated proatherogenic factors.
      Elevations in very low-density lipoprotein (VLDL) enriched with apolipoprotein E
      were equally observed. CONCLUSIONS AND CLINICAL RELEVANCE: Tocilizumab treatment
      led to reductions in proinflammatory components and proatherogenic proteins
      associated with HDL. Whether changes in the proteome of VLDL, LDL, and HDL
      induced by anti-inflammatory tocilizumab treatment in RA patients modify
      cardiovascular disease risk requires further investigation.

PMID- 26201090
TI  - Natural Rabies Infection in a Domestic Fowl (Gallus domesticus): A Report from
      India.
AB  - BACKGROUND: Rabies is a fatal encephalitis caused by viruses belonging to the
      genus Lyssavirus of the family Rhabdoviridae. It is a viral disease primarily
      affecting mammals, though all warm blooded animals are susceptible. Experimental
      rabies virus infection in birds has been reported, but naturally occurring
      infection of birds has been documented very rarely. PRINCIPAL FINDINGS: The
      carcass of a domestic fowl (Gallus domesticus), which had been bitten by a stray
      dog one month back, was brought to the rabies diagnostic laboratory. A necropsy
      was performed and the brain tissue obtained was subjected to laboratory tests for
      rabies. The brain tissue was positive for rabies viral antigens by fluorescent
      antibody test (FAT) confirming a diagnosis of rabies. Phylogenetic analysis based
      on nucleoprotein gene sequencing revealed that the rabies virus strain from the
      domestic fowl belonged to a distinct and relatively rare Indian subcontinent
      lineage. SIGNIFICANCE: This case of naturally acquired rabies infection in a bird
      species, Gallus domesticus, being reported for the first time in India, was
      identified from an area which has a significant stray dog population and is
      highly endemic for canine rabies. It indicates that spill over of infection even
      to an unusual host is possible in highly endemic areas. Lack of any clinical
      signs, and fewer opportunities for diagnostic laboratory testing of suspected
      rabies in birds, may be the reason for disease in these species being undiagnosed
      and probably under-reported. Butchering and handling of rabies virus- infected
      poultry may pose a potential exposure risk.

PMID- 26201091
TI  - An improved assay for (68)Ga-hydroxide in (68)Ga-DOTATATE formulations intended
      for neuroendocrine tumour imaging.
AB  - The objective of this study was to identify a more rapid assay for (68)Ga(OH)3
      impurity in (68)Ga-DOTATATE formulations. Three methods were used to prepare
      (68)Ga(OH)3 reference material (pharmacopoeial, bench titration and automated
      radiosynthesis), and four quality control methods for its assessment (thin layer
      chromatography, membrane filtration, HPLC and solid phase extraction). The
      optimal method of preparing (68)Ga(OH)3 was by titrating (68)Ga(3+) with buffered
      sodium hydroxide solutions to pH 5.6 +/- 0.2. The precipitate was quantitatively
      isolated by membrane filtration (0.02 um)/hydrochloric acid (HCl; pH 5.6)
      solvent, and also it remained 100% at the origin on instant thin layer
      chromatography with silica gel paper/HCl (pH 5.6) solvent. For (68)Ga-DOTATATE
      samples, the thin layer chromatography technique was used with a single paper
      strip developed separately on two occasions, once in HCl (pH 5.6) and next in
      methanol solvent. This so-called double-developed (DD) method separated
      (68)Ga(OH)3 impurity located at the origin, from (68)Ga-DOTATATE plus (68)Ga(3+)
      at ~Rf 0.4, and it was superior to the other methods. It assayed for the impurity
      similarly to the pharmacopoeial method. The advantages of the DD method were that
      it required inexpensive test materials and it reproducibly determined %
      (68)Ga(OH)3 in (68)Ga-DOTATATE in 12 min, 13 min earlier than the pharmacopoeial
      method. This time efficiency resulted in a surplus of 12% (68)Ga-DOTATATE counts
      in the product vial, and this provided a contingency of radioactivity or time for
      the injection/imaging processes in the Nuclear Medicine Department.

PMID- 26201092
TI  - The Hedgehog signalling pathway mediates drug response of MCF-7 mammosphere cells
      in breast cancer patients.
AB  - BCSCs (breast cancer stem cells) have been shown to be resistant to chemotherapy.
      However, the mechanisms underlying BCSC-mediated chemoresistance remain poorly
      understood. The Hh (Hedgehog) pathway is important in the stemness maintenance of
      CSCs. Nonetheless, it is unknown whether the Hh pathway is involved in BCSC
      mediated chemoresistance. In the present study, we cultured breast cancer MCF-7
      cells in suspension in serum-free medium to obtain BCSC-enriched MCF-7 MS (MCF-7
      mammosphere) cells. We showed that MCF-7 MS cells are sensitive to salinomycin,
      but not paclitaxel, distinct from parent MCF-7 cells. The expression of the
      critical components of Hh pathway, i.e., PTCH (Patched), SMO (Smoothened), Gli1
      and Gli2, was significantly up-regulated in MCF-7 MS cells; salinomycin, but not
      paclitaxel, treatment caused a remarkable decrease in expression of those genes
      in MCF-7 MS cells, but not in MCF-7 cells. Salinomycin, but not paclitaxel,
      increased apoptosis, decreased the migration capacity of MCF-7 MS cells,
      accompanied by a decreased expression of c-Myc, Bcl-2 and Snail, the target genes
      of the Hh pathway. The salinomycin-induced cytotoxic effect could be blocked by
      Shh (Sonic Hedgehog)-mediated Hh signalling activation. Inhibition of the Hh
      pathway by cyclopamine could sensitize MCF-7 MS cells to paclitaxel. In addition,
      salinomycin, but not paclitaxel, significantly reduced the tumour growth,
      accompanied by decreased expression of PTCH, SMO, Gli1 and Gli2 in xenograft
      tumours. Furthermore, the expression of SMO and Gli1 was positively correlated
      with the expression of CD44+ / CD24-, and the expression of SMO and Gli1 in CD44+
      / CD24- tissues was associated with a significantly shorter OS (overall survival)
      and DFS (disease-free survival) in breast cancer patients receiving chemotherapy.

PMID- 26201093
TI  - Innate cellular sources of interleukin-17A regulate macrophage accumulation in
      cigarette- smoke-induced lung inflammation in mice.
AB  - Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease
      (COPD). Interleukin-17A (IL-17A) is a pivotal cytokine that regulates lung
      immunity and inflammation. The aim of the present study was to investigate how IL
      17A regulates CS-induced lung inflammation in vivo. IL-17A knockout (KO) mice and
      neutralization of IL-17A in wild-type (WT) mice reduced macrophage and neutrophil
      recruitment and chemokine (C-C motif) ligand 2 (CCL2), CCL3 and matrix
      metalloproteinase (MMP)-12 mRNA expression in response to acute CS exposure. IL
      17A expression was increased in non-obese diabetic (NOD) severe combined
      immunodeficiency SCID) mice with non-functional B- and T-cells over a 4-week CS
      exposure period, where macrophages accumulated to the same extent as in WT mice.
      Gene expression analysis by QPCR (quantitative real-time PCR) of isolated immune
      cell subsets detected increased levels of IL-17A transcript in macrophages,
      neutrophils and NK/NKT cells in the lungs of CS-exposed mice. In order to further
      explore the relative contribution of innate immune cellular sources,
      intracellular IL-17A staining was performed. In the present study, we demonstrate
      that CS exposure primes natural killer (NK), natural killer T (NKT) and
      gammadelta T-cells to produce more IL-17A protein and CS alone increased the
      frequency of IL17+ gammadelta T-cells in the lung, whereas IL-17A protein was not
      detected in macrophages and neutrophils. Our data suggest that activation of
      innate cellular sources of IL-17A is an essential mediator of macrophage
      accumulation in CS-exposed lungs. Targeting non-conventional T-cell sources of IL
      17A may offer an alternative strategy to reduce pathogenic macrophages in COPD.

PMID- 26201094
TI  - Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the
      PI3K/Akt pathway in type 2 diabetic mice and hepatocytes.
AB  - Increased glucose production and reduced hepatic glycogen storage contribute to
      metabolic abnormalities in diabetes. Irisin, a newly identified myokine, induces
      the browning of white adipose tissue, but its effects on gluconeogenesis and
      glycogenesis are unknown. In the present study, we investigated the effects and
      underlying mechanisms of irisin on gluconeogenesis and glycogenesis in
      hepatocytes with insulin resistance, and its therapeutic role in type 2 diabetic
      mice. Insulin resistance was induced by glucosamine (GlcN) or palmitate in human
      hepatocellular carcinoma (HepG2) cells and mouse primary hepatocytes. Type 2
      diabetes was induced by streptozotocin/high-fat diet (STZ/HFD) in mice. In HepG2
      cells, irisin ameliorated the GlcN-induced increases in glucose production,
      phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase)
      expression, and glycogen synthase (GS) phosphorylation; it prevented GlcN-induced
      decreases in glycogen content and the phosphoinositide 3-kinase (PI3K) p110alpha
      subunit level, and the phosphorylation of Akt/protein kinase B, forkhead box
      transcription factor O1 (FOXO1) and glycogen synthase kinase-3 (GSK3). These
      effects of irisin were abolished by the inhibition of PI3K or Akt. The effects of
      irisin were confirmed in mouse primary hepatocytes with GlcN-induced insulin
      resistance and in human HepG2 cells with palmitate-induced insulin resistance. In
      diabetic mice, persistent subcutaneous perfusion of irisin improved the insulin
      sensitivity, reduced fasting blood glucose, increased GSK3 and Akt
      phosphorylation, glycogen content and irisin level, and suppressed GS
      phosphorylation and PEPCK and G6Pase expression in the liver. Irisin improves
      glucose homoeostasis by reducing gluconeogenesis via PI3K/Akt/FOXO1-mediated
      PEPCK and G6Pase down-regulation and increasing glycogenesis via PI3K/Akt/GSK3
      mediated GS activation. Irisin may be regarded as a novel therapeutic strategy
      for insulin resistance and type 2 diabetes.

PMID- 26201095
TI  - Schistosome-induced cholangiocyte proliferation and osteopontin secretion
      correlate with fibrosis and portal hypertension in human and murine
      schistosomiasis mansoni.
AB  - Schistosomiasis is a major cause of portal hypertension worldwide. It associates
      with portal fibrosis that develops during chronic infection. The mechanisms by
      which the pathogen evokes these host responses remain unclear. We evaluated the
      hypothesis that schistosome eggs release factors that directly stimulate liver
      cells to produce osteopontin (OPN), a pro-fibrogenic protein that stimulates
      hepatic stellate cells to become myofibroblasts. We also investigated the utility
      of OPN as a biomarker of fibrosis and/or severity of portal hypertension.
      Cultured cholangiocytes, Kupffer cells and hepatic stellate cells were treated
      with soluble egg antigen (SEA); OPN production was quantified by quantitative
      reverse transcriptase polymerase chain reaction (qRTPCR) and ELISA; cell
      proliferation was assessed by BrdU (5-bromo-2'-deoxyuridine). Mice were infected
      with Schistosoma mansoni for 6 or 16 weeks to cause early or advanced fibrosis.
      Liver OPN was evaluated by qRTPCR and immunohistochemistry (IHC) and correlated
      with liver fibrosis and serum OPN. Livers from patients with schistosomiasis
      mansoni (early fibrosis n=15; advanced fibrosis n=72) or healthy adults (n=22)
      were immunostained for OPN and fibrosis markers. Results were correlated with
      plasma OPN levels and splenic vein pressures. SEA-induced cholangiocyte
      proliferation and OPN secretion (P<0.001 compared with controls). Cholangiocytes
      were OPN (+) in Schistosoma-infected mice and humans. Liver and serum OPN levels
      correlated with fibrosis stage (mice: r=0.861; human r=0.672, P=0.0001) and
      myofibroblast accumulation (mice: r=0.800; human: r=0.761, P=0.0001). Numbers of
      OPN (+) bile ductules strongly correlated with splenic vein pressure (r=0.778;
      P=0.001). S. mansoni egg antigens stimulate cholangiocyte proliferation and OPN
      secretion. OPN levels in liver and blood correlate with fibrosis stage and portal
      hypertension severity. 

PMID- 26201097
TI  - Effect of Prophylactic Ankle-Brace Use During a High School Competitive
      Basketball Season on Dynamic Postural Control.
AB  - CONTEXT: Few studies have evaluated the long-term effects of prophylactic ankle
      brace use during a sport season. OBJECTIVE: To determine the effects of
      prophylactic ankle-brace use during a high school basketball season on dynamic
      postural control and functional tests. DESIGN: Prospective repeated-measures
      design. SETTING: High school athletic facility. PARTICIPANTS: 21 healthy high
      school basketball athletes (13 girls, 8 boys). INTERVENTIONS: The order of
      testing was randomized using the Star Excursion Balance Test (SEBT) for
      posteromedial (PM), medial (M), and anteromedial (AM) directions and 3 functional
      tests (FT) consisting of the single-leg crossover hop, single-leg vertical jump,
      and the single-leg 6-m hop for time at pre-, mid-, and postseason. After
      pretesting, the ankle brace was worn on both limbs during the entire 16-wk
      competitive basketball season. MAIN OUTCOME MEASURES: SEBT for PM, M, and AM and
      3 single-leg FTs. RESULTS: Dynamic postural control using the SEBT and the 3 FTs
      improved over time, notably from pretest to posttest. The left limb was different
      from the right limb during the single-leg vertical jump. Effect sizes were large
      for pretest to posttest for the 3 SEBT directions and 2 of the 3 FTs.
      CONCLUSIONS: The 16-wk basketball prophylactic ankle-brace intervention
      significantly improved dynamic postural control and single-limb FTs over time.

PMID- 26201096
TI  - Klotho expression is reduced in COPD airway epithelial cells: effects on
      inflammation and oxidant injury.
AB  - COPD (chronic obstructive pulmonary disease) is associated with sustained
      inflammation, excessive injury, and accelerated lung aging. Human Klotho (KL) is
      an anti-aging protein that protects cells against inflammation and damage. In the
      present study, we quantified KL expression in the lungs of COPD patients and in
      an ozone-induced mouse model of COPD, and investigated the mechanisms that
      control KL expression and function in the airways. KL distribution and levels in
      human and mouse airways were measured by immunohistochemistry and Western
      blotting. The effect of CSE (cigarette smoke extract) on KL expression was
      detected in human bronchial epithelial cells. Moreover, the effect of KL on CSE
      mediated inflammation and hydrogen peroxide-induced cellular injury/apoptosis was
      determined using siRNAs. KL expression was decreased in the lungs of smokers and
      further reduced in patients with COPD. Similarly, 6 weeks of exposure to ozone
      decreased KL levels in airway epithelial cells. CSE and TNFalpha (tumour necrosis
      factor alpha) decreased KL expression and release from airway epithelial cells,
      which was associated with enhanced pro-inflammatory cytokine expression.
      Moreover, KL depletion increased cell sensitivity to cigarette smoke-induced
      inflammation and oxidative stress-induced cell damage. These effects involved the
      NF-kappaB (nuclear factor kappaB), MAPK (mitogen-activated protein kinase) and
      Nrf2 (nuclear factor erythroid 2-related factor 2) pathways. Reduced KL
      expression in COPD airway epithelial cells was associated with increased
      oxidative stress, inflammation and apoptosis. These data provide new insights
      into the mechanisms associated with the accelerated lung aging in COPD
      development.

PMID- 26201098
TI  - [Chemical Components, Mercury Coordination Structure and Micro-Morphology of
      Tibetan Medicine Zuotai].
AB  - In order to reveal the chemical substance basis of pharmacodynamic effects of
      Zuotai, energy dispersive spectrometry of X-ray (EDX), X-ray fluorescence
      spectroscopy (XRF), synchrotron radiation X-ray absorption fine structure (SR
      XAFS), X-ray diffraction (XRD), scanning electron microscope (SEM) and atomic
      force microscope (AFM) were used to analyze the elements, the chemical valence
      and local structure of mercury, and the chemical phase composition and micro
      morphology of Zuotai. EDX and XRF analysis shows that the main elements in Zuotai
      are Hg and S, with some other minor elements, such as 0, Fe, Al, Cu, K, Ag, Ca,
      Mg etc. SR-XAFS analysis shows that: the oxidation state of mercury in Zuotai is
      divalence, its neighbor atoms are S, and its coordination number is four. XRD
      assay found that beta-HgS (cubic, F-43m 216) and S8 (orthorhombic, Fddd 70) are
      the main phase compositions in Zuotai. Besides, it also has a small amount of C
      (hexagonal, P63/mmc 194), Fel.05 S0.95 (hexagonal, P63/mmc 194), Cu6S6
      (hexagonal, P63/mmc 194), Cu1.8 S (cubic, F-43m 216) and so on. And it was found
      that the crystallinity of Zuotai is about 59%, and the amorphous morphology
      substance in it is about 41%. SEM and AFM detection suggests that Zuotai is a
      kind of ancient micro-nano drug, and its particle size is mainly in the range of
      100-600 nm, even less than 100 nm, which commonly further aggregate into several
      to 30 um loose amorphous particles. In summary, the present study elucidated
      physicochemical characterization(elements composition, coordination information
      of mercury, phase composition and micro-morphology) of Zuotai, and it will play a
      positive role in promoting the interpretation of this mysterious drug.

PMID- 26201099
TI  - 'Normality' in 2015: one midwife's response.

PMID- 26201100
TI  - Authors' reply.

PMID- 26201101
TI  - Authors' reply.

PMID- 26201102
TI  - Authors' response.

PMID- 26201103
TI  - [The Regulatory Proteins of beta-Adrenergic Receptor and Their Functions].
AB  - Vascular diseases has become a top killer of human health, and cardiovascular
      receptors are pivotal in the occurrence, development, prevention and treatment of
      cardiovascular diseases. As for the important member of G protein-coupled
      receptor, beta-adrenergic receptor is undoubtedly a most important target of
      cardiovascular drugs. Being the hot spot in the cardiovascular research and
      application, beta- adrenergic receptor blocker has been considered as the
      greatest breakthrough for the prevention and cure of cardiovascular disease after
      digitalis. The 2012 Nobel Prize in chemistry was awarded again to the researchers
      on beta-adrenergic receptors. Extensive researchs show that beta-adrenergic
      receptors are precisely regulated by different regulatory proteins in cells in
      the transduction of different physiological and pathological signaling pathways.
      Based on these findings, function-selective ligands recently arise in the
      receptor research and will be the new chance of drug discovery. In this article
      we reviewed the related signal pathways and functions of beta-adrenergic receptor
      regulatory proteins.

PMID- 26201104
TI  - [Stem Cell in Cardiac Repair and Regeneration: Current Status and Challenge].
AB  - In the context of a growing pandemic of myocardial infarction (MI), the current
      standard therapies cannot provide an ideal outcome for the patients. Hence, novel
      approaches are being explored to identify curative treatment. In recent years,
      stem cell has been regarded as a critical source for cardiac regeneration, and
      several types of stem cells have been demonstrated with cardiogenic capacity. To
      date, thousands of patients with MI have received autologous stem cells therapy,
      but the benefits were modest. In this review, we summarize the recent findings of
      stem cells therapy in cardiac repair and regeneration, and propose the key
      unsolved hurdles in this field.

PMID- 26201105
TI  - [Regulation of glucose metabolism by mTOR signaling].

PMID- 26201106
TI  - [The origins of adipocyte].

PMID- 26201107
TI  - [Research progress of glycerol-3-phosphate acyltransferases (GPATs)].

PMID- 26201108
TI  - [The role of Epac in kidney tuble physiology].

PMID- 26201109
TI  - [The role of endoplasmic reticulum stress in diabetic nephropathy].

PMID- 26201110
TI  - [Molecular mechanism and regulation of GLP-1 production].

PMID- 26201111
TI  - [The relationship between vitamin D, inflammation and T2DM].

PMID- 26201112
TI  - [The role of adventitial inflammation in vascular remodeling].

PMID- 26201114
TI  - [The research progress of genes associated with Parkinson's disease].

PMID- 26201113
TI  - [The mechanism and application of hypoxia injury induced by cobalt chloride in
      neurons].

PMID- 26201115
TI  - [Protective roles of exercise training on ventricular remodeling after myocardial
      infarction].

PMID- 26201116
TI  - [The distribution and significance of hyperpolarization-activated cyclic
      nucleotide-gated channel in the nervous system].

PMID- 26201117
TI  - [Role of pedunculopontine nucleus in parkinson's disease].

PMID- 26201118
TI  - [The ADAR-mediated RNA editing in the nervous system diseases].

PMID- 26201119
TI  - [The role of long non-coding RNA in physiologic and pathological regulation of
      cardiomyocytes].

PMID- 26201120
TI  - IS THERE A DIFFERENCE IN THE INCIDENCE OF HELICOBACTER PYLORI INFECTION IN
      PATIENTS WITH SOME CHRONIC DISEASES?
AB  - Globally, Helicobacter pylori infection is estimated to be present in two-thirds
      of the population. This longitudinal, observational, comparative case-control
      study conducted in the county of Brasov on 763 subjects split into two groups:
      one with Helicobacter pylori infection (412 people) and the other without
      infection (351 people) allowed us to compare our results with other international
      epidemiological studies. Thus, statistical interpretation of results indicates
      diabetes as an indifferent factor in the interrelation with Helicobacter pylori
      infection, while asthma and hypertension might be considered as protective
      factors.

PMID- 26201121
TI  - SERUM ALPHA FETOPROTEIN, A SURROGATE MARKER FOR LIVER DISEASE PROGRESSION IN
      CHRONIC HEPATITIS C.
AB  - Serum alpha fetoprotein (AFP) is a commonly used marker in the screening for
      hepatocellular carcinoma. This study aims to evaluate the value of AFP as an
      early predictor of the evolution of chronic hepatitis C. In a retrospective study
      on 116 HCV-infected patients (62.9% females, mean age 49.13 +/- 1.73 years),
      increased levels of serum AFP (> 7 ng/mL) were found in 39.7% of cases. High
      serum AFP levels were more frequently detected in older patients and in those
      with severe fibrosis and cirrhosis (62.2% and 76.9% respectively vs. 11.6% in
      those without significant fibrosis, p = 0.0001). Increased AFP levels were
      significantly associated with markers of hepatic cytolysis (ALT- r = 0.245, p =
      0.009 and AST r = 0.441, p = 0.0001) and cholestasis (GGT level-r = 0.947, p =
      0.000 1), but not with HCV viral load. A predictive model based on AFP level and
      routinely monitored biochemical markers of liver fibrosis and necroinflammatory
      activity can be a useful clinical tool in chronic HCV infection.

PMID- 26201122
TI  - MOLECULAR CHARACTERIZATION OF STAPHYLOCOCCUS AUREUS STRAINS ISOLATED FROM
      INFECTIVE ENDOCARDITIS.
AB  - Infective endocarditis (IE) is an infection of the heart endothelium and valves
      and is frequently a consequence of a sanguine flow turbulence and injury of
      endocardium. Recent studies revealed an increase of Staphylococcus aureus strains
      involved in IE, but no evident correlations between the genetic background of
      this bacterium and IE involvement of certain strains have been found yet. In this
      study we analyzed the virulence profile, including adhesins, exotoxins,
      superantigens and biofilm determinants, along with agr type detection, for S.
      aureus strains isolated from IE, versus non-IE originating strains. We performed
      also bacterial typing (SCCmec typing, spa-typing and MLST typing), in order to
      compare our strains with international databases repositories. Although the study
      was carried out on a reduced number of isolates, our observations confirm the
      previous works, showing that no major differences were observed between the
      genetic backgrounds of the two groups of strains analyzed. Notably, the added
      value of this study was optimization of two new multiplex PCR protocols, and the
      enrichment of international databases with three new spa-types, three new MLST
      alleles and four new MLST sequence types.

PMID- 26201123
TI  - MICRORNA BIOGENESIS AND ITS ROLE IN HIV-1 INFECTION.
AB  - MicroRNA (miRNA) are small- 19-24 nucleotides, non-coding RNA molecules that
      regulate translational and post-translational processes through mRNA degradation
      and protein translation repression, or sometimes through heterochromatin
      formation or activation of protein translation. Lately, miRNA are investigated as
      predictive biomarkers for the evolution and prognosis of viral diseases, as well
      as therapeutic targets. Although the role of non-coding RNA molecules during HIV
      infection is not yet fully elucidated, several studies have reported strong
      correlations between cellular and viral miRNA expression and the immunologic and
      virological status of infected patients. Some studies have proven the existence
      of host cellular miRNA able to influence all important steps in HIV replicative
      cycle and to interfere with the establishment of latent infection in CD4+ cells.
      Although the function and existence of viral encoded miRNA remains controversial,
      new studies have shown their potential in modulating the host cell response or
      the efficiency of viral replication. This review aims to summarize the current
      level of knowledge in the interaction between miRNA and HIV-1 and to describe new
      therapeutic strategies entailing miRNAs as new and potent players in controlling
      viral infectivity, replication and latency.

PMID- 26201124
TI  - MECHANISMS OF THROMBOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS.
AB  - Thrombotic events are highly prevalent in systemic lupus erythematosus (SLE).
      Antiphospholipid antibodies play an essential role in promoting thrombosis by
      activating several intracellular signaling pathways (TLR4, p38MAPK, NFkB) in
      platelets, monocytes and endothelial cells. New therapeutic opportunities might
      be offered by addressing these molecular targets. Chronic inflammatory status,
      the degree of disease activity and accelerated atherosclerosis are also
      responsible for the thrombotic phenotype in patients with SLE. The aim of this
      review is to highlight thrombosis mechanisms and to look for possible connection
      between SLE, antiphospholipid antibodies and cancer, especially
      myeloproliferative neoplasms.

PMID- 26201125
TI  - ROMANIAN SCIENTISTS IN THE NOMINATION DATABASE FOR THE NOBEL PRIZE IN PHYSIOLOGY
      OR MEDICINE, 1901-1951.
AB  - Nobelprize.org site is the most reliable and complete resource of information on
      the Nobel Prize and the Nobel Laureates. The nomination database for Physiology
      or Medicine, 1901-1951, offers exciting facts about the Romanian Schools of
      Medicine from Bucharest, Iasi and Cluj. Between 1920-1950, four Romanian
      scientists were nominated for the Nobel Prize: Victor Babes (1854-1926), Ion
      Cantacuzino (1863-1934), Thoma Ionescu (1860-1926) and Constantin Levaditi (1874
      1953). This paper discusses these nominees, the nominators and the motivations,
      as well as the specific publications that endorse the candidates' scientific
      activity. Recommendations made by Romanian professors for foreign researchers to
      receive the Nobel Prize are also included.

PMID- 26201126
TI  - ROLE OF SALMONELLA SEROLOGY A CENTURY AFTER THE WIDAL ERA.
AB  - Typhoid fever remains an important health burden in the developing world, whereas
      non-typhoid salmonelloses are one of the most common food-borne illnesses
      throughout the world and can be subjected to extra-intestinal complications.
      Culture is the gold standard for diagnosing a Salmonella infection. Serology can
      also provide evidence of infection. Serological methods for the diagnosis of
      Salmonella infections in humans and animals vary widely and can as well be used
      in epidemiologic studies to detect carriers, to assess infection rates, disease
      burden and vaccine responses. As with all serology, detecting antibody titers in
      Salmonella infections has its limits, mainly related to low sensitivity and
      specificity, high running costs, and antibody kinetics and peculiarities. Fast
      and more or less reliable immunoassays which detect Salmonella enterica serovar
      Typhi are commercially available. Veterinary and food sectors are well-provided
      with commercially tests for non-typhoid salmonellosis, while most immunoassays
      for non-typhoid human Salmonella diagnosis are developed and used in-house mainly
      for research or surveillance purposes. So far, there is no international
      consensus for the development of such serological tests for routine diagnostics.
      119 years after the observations made by George Fernand Isidore Widal, this work
      intends to review and analyze the present state of facts and controversies in the
      field of Salmonella serology.

PMID- 26201127
TI  - Home Healthcare Program for Soil-Transmitted Helminthiasis in Schoolchildren
      along the Mekong River Basin.
AB  - BACKGROUND: Soil-transmitted helminths (STH) are among the most important groups
      of infectious agents responsible for physical and intellectual growth retardation
      in children worldwide. Current status is need requiredfor the development of
      control programs. OBJECTIVE: To determine the STH infections among the
      schoolchildren in the Mekong River basin near rural Ubon Ratchathani, Thailand
      and Champassak, Laos PDR, including their caregiver knowledge and attitude
      concerning prevention of STH infections. MATERIAL AND METHOD: A cross sectional
      survey was designed as a home healthcare programfrom October 2009 to April 2012.
      1,957 fecal samples were collected from children aged 5-12 years in five
      districts of Ubon Ratchathani province (1,012 fecal samples; Khong Chiam, Si
      Mueang Mai, Phibun Mangsahan, Sirindhorn, and Pho Sai), Thailand, and one
      district of Champassak Province (945 fecal samples; Pakse), Lao PDR. Fecal
      samples were prepared by the modified formalin ethylacetate concentration
      technique, and determined by light microscope. The knowledge and attitude of
      children's caregivers concerning prevention of soil-transmitted helminth
      infections were completed interviewed by semi-structured questionnaires. RESULTS:
      The overall intestinal helminth prevalence rate was 11.88%. Classified by species
      the STHs were as follows: Ascaris lumbricoides (30.9%), Trichuris trichiura
      (21.7%), and hookworm (20.5%). The highest prevalence was recorded in children
      aged 9 years and above. The highest prevalence of STH infection was found in the
      Pakse district of Laos PDR (16.08%). The intensities of infection with A.
      lumbricoides, T trichiura, and Hookworm were 1.82 +/- 0.36, 1.32 +/- 0.30, and
      1.29 +/- 0.32, respectively. 1,077 of caregivers were completed interviewed and
      found that the caregivers had fair levels of knowledge and attitude regarding
      soil-transmitted helminthiasis. CONCLUSIONS: These results suggest that priority
      should be given to STH eradication, the development of control programs in the
      Mekong River Basin, and the provision of education about STH to caregivers to
      reduce the risk of STH infection in their schoolchildren.

PMID- 26201128
TI  - Localization of Tubulin from the Carcinogenic Human Liver Fluke, Opisthorchis
      viverrini.
AB  - BACKGROUND: Opisthorchiasis caused by Opisthorchis viverrini, is of considerable
      public health importance in Southeast Asia, particularly in Lao People's
      Democratic Republic and Thailand. The infection is associated with a number
      ofhepatobiliary diseases including cholangitis, obstructive jaundice,
      hepatomegaly, cholecystitis, cholelithiasis and cholangiocarcinoma. OBJECTIVE:
      This study aims to localize the expression sites of 0. viverrini tubulin using
      immunohistochemistry by monoclonal anti alpha-tubulin (MAalphaT) and anti beta
      tubulin (MAbetaT). MATERIAL AND METHOD: The adult worms of O. viverrini, and the
      adult worm of O. viverrini in biliary system of hamsters were fixed, cryo
      sectioned and then immunohistochemically stained. The sections were incubated
      with MAalphaTor MAbetaT. A positive test required the observation of brown
      staining in the fluke's organs. RESULTS: The immunohistochemistry of MAalphaT and
      MAbetaT in adult worms of O. viverrini, and the adult worm of O. viverrini in
      biliary system of hamsters strongly expresses in the sperm and seminal vesicles
      of the worm. MAalphaT and MAbetaT expressed slightly in sub-tegumental tissue,
      stromalparenchyma, muscle fibers, and miracidium in the mature egg of the worm.
      No staining in the spermatogonia, gut epithelium, immature egg, tegument or
      vitelline glands of the worm nor in the hamster bile duct epithelium was seen.
      CONCLUSION: The present study indicates that O. viverrini tubulin is present in
      the reproductive organs and other important organs of the worm. Because it plays
      a key role in the biological processes of cellular motility and fertility it
      should be further studied in detail including the characterization, production of
      recombinant proteases, and their application in immunodiagnosis.

PMID- 26201129
TI  - Malaria Risk Areas in Thailand Border.
AB  - BACKGROUND: Malaria is a serious public health problem of the world especially in
      Africa and Asia where the areas are located in the tropical and subtropical
      regions. Malaria is a mosquito-borne infectious disease ofhumans caused by
      parasitic protozoans of the genus Plasmodium. OBJECTIVE: The present study aims
      to analyze the risk areas by using Potential Surface Analysis (PSA) with
      Geographic Information Systems (GIS) in Thai-Cambodia border including Buriram
      and Surin provinces. MATERIAL AND METHOD: The study divided the factors into six
      factors including population density, land used (agriculture, houses, water
      reservoirs, forest), anopheles adult density in villages with reported cases,
      average annual rainfall, average annual temperature, average annual relative
      humidity and analyzing risk areas by analysis of PSA. RESULTS: 846 malaria cases
      were reported between 2008 and 2012, 80.50% and 19.50% from to the Surin and
      Buriram provinces, respectively. The most cases were found in females, in the 31
      40-year age group and agricultural people. The predominant cases were Plasmodium
      vivax with 45.36%. The high-risk areas of malaria cases was on the 3,014.79
      kilometer Thai-Cambodian border consisting offour districts: Nangrong and
      Nondaeng districts of Buriram province and Sangka and Buached districts of Surin
      province. The relationship between malaria morbidity with environmental factors
      found that malaria morbidity rates were associated with land use (forest areas),
      population density, anopheles adult density of statistical significance and
      influenced morbidity rates by 12.3% (Adjusted R2 = 0.261), 17.0 (Adjusted R2 =
      0.170), and 11.1 (Adjusted R2 = 0.111). The climate factor associated to malaria
      morbidity with average annual relative humidity by percentage of 5.7 (Adjusted R2
      = 0.057). CONCLUSION: This study showed that malaria is still a problem in
      Thailand-Cambodia border and the analysis of PSA with GIS can be used to assess
      the risk of malarial morbidity, and lead to planning, control, and prevention of
      the morbidity.

PMID- 26201130
TI  - Risk Areas of Liver Flukes in Surin Province of Thailand using Geographic
      Information System.
AB  - BACKGROUND: Opisthorchiasis, caused by Opisthorchis viverrini, is of considerable
      public health importance in Southeast Asia, particularly in Lao PDR and Thailand.
      OBJECTIVE: This study aims to analyze the risk areas for liver flukes in Surin
      province, Thailand using Geographic Information Systems (GIS). MATERIAL AND
      METHOD: The 5 main factors (131 variables) were: (1) personal data (2) knowledge,
      attitude and practice, (3) health service unit, (4) environmental data, and (5)
      climate data. The relationship between these mainfactors and liver fluke
      infection was analyzed using multiple regression analysis. Potential surface
      analysis (PSA) with geographic information systems (GIS) was performed to create
      maps displaying areas at risk for liver fluke infection in Surin province.
      RESULTS: The population density (148-169 pop/km2; X73), human attitude (< 50%;
      X111), and land use (wetland; X64), were statistically significant with liver
      fluke infection by a percentage of 88.60% (Adjusted R2 = 0.886). The heavy risk
      areas covered 221.39 km2 and including 8 districts; Si Narong, Sangkha, Phnom
      Dong Rak, Mueang Surin, Non Narai, Samrong Thap, Chumphon Buri and Rattanaburi.
      CONCLUSION: Present study identifies the increased risk areas for liver flukes in
      Surin Province and may be useful for future planning of prevention and control.

PMID- 26201131
TI  - A Cross-Sectional Survey of Intestinal Helminthiases in Rural Communities of
      Nakhon Ratchasima Province, Thailand.
AB  - BACKGROUND: The public-health problems caused by intestinal helminthic infections
      have been neglected in rural areas where there remains a lack of hygiene and an
      inadequate supply ofsanitary water OBJECTIVE: This research was to study the
      infection rate of intestinal helminthiases and socioeconomic data within two
      communities in Nakhon Ratchasima province. MATERIAL AND METHOD: Intestinal
      helminthiases were examined using Kato's Thick Smear technique and socio
      demographic data was collected using predesigned semi-structured questionnaires.
      RESULTS: 209 stool samples were collected from 83 male and 126 female
      participants. Stool examinations showed that 6.22% (13/209) of study participants
      were infected with intestinal helminths, predominantly hookworm (4.31%, 9/209)
      followed by Strongyloides stercolaris (1.44%, 2/209), and Taenia sp. (0.48%,
      1/209). Males were slightly more likely to be infected than females. Intestinal
      helminthic infection was more commonlyfound in the 61-70 year age group
      andpositively associated with occupation ofagriculture. The Tanod sub-district
      had an intestinal helminthiases rate of 10.59%, higher than in the Wang Sai sub
      district. In conclusion, this study shows that intestinal helminthic infections
      are common parasitic infections among patients presenting for a small scale
      survey of a rural Thai community. CONCLUSION: This information may provide
      invaluable statistics needed for planning meaningful public control programs that
      aim at reducing the prevalence and morbidity of parasitic infections. Large scale
      surveys and health education are urgently required.

PMID- 26201132
TI  - Comparison of Cryopreserved Human Sperm between Ultra Rapid Freezing and Slow
      Programmable Freezing: Effect on Motility, Morphology and DNA Integrity.
AB  - BACKGROUND: Cryopreservation of sperm is common methods to preserve male
      fertility. Sperm freezing, suggest slow programmable freezing caused lower change
      of sperm morphology than sperm freezing in vapor of liquid nitrogen. Ultra rapid
      freezing is easy to be worked on, less time, low cost and does not need high
      experience. OBJECTIVE: To compare the effect on sperm motility, morphology and
      DNA integrity of post-thawed sperm after ultra rapid freezing and slow
      programmable freezing methods. MATERIAL AND METHOD: Experimental study at
      laboratory of infertility unit, Department of Obstetrics and Gynecology, Faculty
      of Medicine Ramathibodi Hospital. Thirty-seven semen samples with normal semen
      analysis according to World Health Organization (WHO) 1999 [normal sperm volume (
      2 ml) and normal sperm concentration (>= 20 x10(6)/ml) and sperm motility (>=
      50%)]. Semen samples were washed. Then each semen sample was divided into six
      cryovials. Two cryovials, 0.5 ml each, were cryopreserved by slow programmable
      freezing. Four 0.25 ml containing cryovials, were cryopreserved by ultra
      rapidfreezing method. After cryopreservationfor 1 month, thawedprocess was
      carried out at room temperature. Main outcomes are sperm motility was determined
      by Computer-Assisted Semen Analysis (CASA), sperm morphology was determined by
      eosin-methylene blue staining and sperm DNA integrity was assessed by TUNEL
      assay. RESULTS: Sperm motility was reduced significantly by both methods, from
      70.4 (9.0)% to 29.1 (12.3)% in slowprogrammable freezing and to 19.7 (9.8)% in
      ultra rapid freezing (p < 0.05). Sperm motility decreased significantly more by
      ultra rapid freezing (p < 0.001). The percentage of normal sperm morphology and
      DNA integrity were also reduced significantly by both methods. However, no
      significant difference between the two methods was found (p > 0.05). CONCLUSION:
      Cryopreservation of human sperm for 1 month significantly decreased sperm
      motility, morphology and DNA integrity in both methods. However sperm motility
      was decreased more by ultra rapid freezing.

PMID- 26201133
TI  - Decisions of Pregnant Adolescents Towards Antenatal Care Attendance and Their
      Immediate Postpartum Adaptation: Comparison between Students and Other
      Occupations.
AB  - BACKGROUND: Adolescent pregnancy is risky with multiple complications during
      pregnancy and the delivery period. Adolescent pregnancy among students is more
      risky because the mothers did not intend to get pregnant, have poor relationship
      with the husband and do not take care of their child themselves as in other
      occupations. OBJECTIVE: The decisions of adolescent mothers towards antenatal
      care (ANC) attendance and their postpartum adaptation; comparing students with
      other occupations MATERIAL AND METHOD: This retrospective hospital-based study
      used data from the records of 777 adolescent mothers who attended the adolescent
      postpartum clinic at Maharat Nakhon Ratchasima Hospital from January 2012 to
      December 2013. The data were classified into students and other occupation
      groups. Their decisions for ANC attendance, spousal relationship, pregnancy
      intentions, family acceptance and postpartum adaptation (contraceptive decision,
      decision for taking care of baby and returning to study) from both groups were
      compared and analyzed. RESULTS: The prevalence of student mothers was 63.3% of
      all adolescent pregnancies. The following factors were more common in student
      mothers with statistical significance, odd ratio (95% confidence interval):
      unintended pregnancy 3.66 (2.45-5.47), family non-acceptance 1.71 (1.03-2.93),
      poor ANC (no ANC and ANC after 12 weeks) 22.82 (14.33-37.34). Other factors
      including no ANC attendance, decision for taking care of the baby, contraceptive
      decision (before and after deliveries), and the contraceptive method was no
      different between the groups. After delivery, adolescents decided to return to
      their studies; 58.7% for students and 33.3% for other occupation groups.
      CONCLUSION: Students account for 63.3% of all adolescent pregnancies. None of
      them was married so the majority did not intend to be pregnant and not be
      accepted by their families, leading to poor ANC attendance. Half of them decided
      to return to their studies. Further studies should be prospectively performed at
      schools to see the true prevalence of pregnancy and the related factors such as
      pregnancy termination, withdrawal from school and the continuation of their
      studies.

PMID- 26201134
TI  - Association between Subclinical Atherosclerosis among Hyperlipidemia and Healthy
      Subjects.
AB  - BACKGROUND: The global burden ofcardiovascular disease (CVD) continues to rise as
      developing nations. Primary prevention is effective in populations traditionally
      considered low-risk. Carotid intima-media thickness (CIMT) is considered as a
      surrogate marker for CVD. OBJECTIVE: Correlation between surrogate markers of
      subclinical atherosclerosis CIMT, carotid plaque and CVD risk factors in
      hyperlipidemia and healthy group. MATERIAL AND METHOD: Cross sectional study,
      aged 18-80 years from cardiovascular clinic, Suranaree University of Technology
      Hospital and measurement CIMT Correlates between CIMT and traditional CVD risk
      factors age, gender; body mass index (BMI), Waist hip ratio (WHR), total
      cholesterol, triglyceride, HDL-cholesterol level, LDL-cholesterol level were
      assessed in the entire population. RESULTS: Population 302 subjects (male 154
      [51%]), mean age 47.17 +/- 10.95 years were found to be hyperlipidemia 216
      (71.5%) and healthy 86 (28.5%) subjects. Comparability between hyperlipidemia and
      healthy subject not different in BMI, WHR, and FBS. Mean left and right CIMT no
      difference between hyperlipidemia and healthy subjects. CIMT correlated with
      hyperlipidemia higher LDL-cholesterol level (r = 0.12, p = 0.03), triglyceride (r
      = 0.18 p < 0.01), WHR (r = 0.19, p < 0.01) and SBP (r = 0.2 2, p < 0.01). The
      correlation coefficients were not significantly different between CIMT and
      traditional risk factors age, gender; BMI, LDL-C and HDL-C. CONCLUSION: The
      subclinical atherosclerosis CIMTvalues are closely associated with hyperlipidemia
      along with cholesterol, triglyceride, WHR and SBP.

PMID- 26201135
TI  - Plasma Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol
      Concentration Ratio and Early Marker of Carotid Artery Atherosclerosis.
AB  - BACKGROUND: Carotid intima-media thickness (CIMT) is a surrogate markerfor
      cardiovascular disease (CVD) and LDL-C/ HDL-C ratio is related to CIMT or carotid
      plaque. Evaluate early atherosclerosis markers whether elevated levels of the LDL
      C/HDL-C ratio is a more significant predictor than LDL-C or HDL-C alone.
      OBJECTIVE: To assess the correlation between early atherosclerosis markers using
      CIMT carotid plaque, carotidplaque type and LDL/HDL ratio surrogate maker and LDL
      C/HDL-C ratio. MATERIAL AND METHOD: Cross sectional study. Aged 18-80 years in
      cardiovascular clinic, Suranaree University of Technology, Thailand CIMT carotid
      plaque and carotid plaque type were measured using a B-mode ultrasonography,
      ratio LDL/HDL, Framingham risk score and traditional CVD risk factors (age, body
      mass index (BMI), Waist hip ratio (WHR), gender total Cholesterol, triglyceride,
      HDL-C, LDL-C) were assessed in the entire population. RESULTS: Population of 302
      subjects (154 (51%) male) mean age (47.17 +/- 10.95 years) was recruited. The
      mean CIMT 0.71 mm (min 0.46 mm and max 1.22 mm). CIMT correlated with WHR (p <
      0.01), SBP (p < 0.01), total cholesterol (p = 0.032), triglyceride (p < 0.01) but
      not with LDL/HDL ratio, other traditional risk factors BMI, FBS, LDL-C and HDL-C.
      Carotid plaque showed association only with triglyceride (p = 0.011). Carotid
      plaque type showed association with age (p < 0.01), sex (0.03), Framingham risk
      score (p = 0.03), WHR (P = 0.01) and SBP (p < 0.01). CONCLUSION: No association
      between early atherosclerosis CIMT carotid plaques, carotid plaque type with
      LDL/HDL ratio identified but closely associated with WHR.

PMID- 26201136
TI  - Perceptions of Medical Students and Facilitators of an Early Clinical Exposure
      Instructional Program.
AB  - BACKGROUND: Early introduction to clinical medicine program was use as medical
      curriculum, Suranaree University since 2007. Today, medical students are learning
      introduction to patient contact, communication skills and clinical examination in
      the pre-clinicalyears with the purpose ofgaining early clinical experience.
      OBJECTIVE: Investigation for pre-clinical students and clinical facilitators'
      perception through early introduction to clinical medicine. MATERIAL AND METHOD:
      Third-year medical students were enrolled in the introduction to clinical
      medicine coursefor 2 weeks. Questionnaires for student andfacilitator versions
      were distributed to 60 students and 21 facilitators. In the analysis, both t-test
      analysis and bivariate analysis for mean difference were used, statistical
      significant p < 0.05. RESULTS: Sixty students (participation rate 100%) and 16
      'facilitators (participation rate 76%) completed the questionnaire. Differences
      in perception between medical students and facilitators were found in domains of
      professionalism, facilitator's perception were greater than medical students in
      medical profession were (4.5 vs. 3.87, p = 0.03), domain that medical student's
      perception were greater than facilitator's in encouragement was (3.95 vs. 3.25, p
      < 0.01) and pressure in learning environment (3.92 vs. 3.12, p < 0.01). No
      learning gaps of facilitators and medical students in the other domains
      ofcognitive, interpersonal skills, ethics, learning, teacher preparation and
      social environment and overall stratification were identified. CONCLUSION: The
      students experienced the course as providing them with a valuable introduction to
      the physician professional role in clinical practice. In medical students'
      perception, they often experienced encouragement and the learning environment
      more so thanfacilitators did. Overall stratification was good in perception of
      facilitators and medical students.

PMID- 26201137
TI  - Risk Factors of Small for Gestational Age and Large for Gestational Age at
      Buriram Hospital.
AB  - BACKGROUND: Babies with low birth weight, small for gestational age (SGA) and
      large for gestational age (LGA) are at increased risk of many perinatal
      complications. OBJECTIVE: To evaluate the risks factors associated with SGA and
      LGA births at Buriram Hospital. MATERIAL AND METHOD: Pregnant women who were
      admitted to the labor room at Buriram hospital were selected, alternate cases in
      the daytime between October 2012 and January 2013. Pre-pregnancy BMI and
      gestational weight gain were categorized based on Institute of Medicine BMI
      groups. The predicted risk of either SGA or LGA births were estimated using
      generalized linear modeling and multivariate regression. RESULTS: Data were
      collected on 197 pregnant women including pregnancy characteristics, antenatal
      care, labor characteristics, maternal complications and neonatal health. The
      average maternal age was 25.74 +/- 6.47 years old. The results showed that the
      factors of weight gain during pregnancy < recommend for the pre-pregnancy BMI
      weight, gestational age < 37 weeks and pregnancy induce hypertension were
      correlated with SGA by logistic regression. Maternal age < 19 years old was
      correlated with a lower incidence of LGA. When using multivariate analysis the
      factor associated with SGA was gestational age < 37 weeks (Adjusted odds ratio
      10.403, 95% CI 2.109-51.313, p = 0.004), whereas the factor associated with
      decreased LGA was maternal age < 19 years old (Adjusted odds ratio 0.128, 95% CI
      0.017-0.983, p = 0.048). CONCLUSION: The risk factor associated with SGA was
      gestational age < 37 weeks. The factor associated with LGA was maternal age, with
      maternal age < 19 years old having the least incidence for LGA. Public health
      programs should be targeted towards improving antenatal care screening and close
      monitoring including maternal age, gestational weight gain, monitoring obstetric
      care, prevent preterm delivery and providing proper newborn resuscitation in
      order to decrease perinatal complications and improve the quality of perinatal
      health.

PMID- 26201138
TI  - The Effect of the Arm Swing on the Heart Rate of Non-Athletes.
AB  - BACKGROUND: The Arm Swing Exercise (ASE) is a style of alternative medicine. The
      ASE normally follows the pattern of swing forward 30 degrees and then swing
      backward 60 degrees for each swing. It is thought that practicing the ASE can
      improve musculoskeletal performance. OBJECTIVE: The purposes of this study were:
      1) to compare the difference in mean number of arm swings, heart rates and energy
      expenditures between the groups, 2) To examine the effect of basic
      characteristics and number of arm swing on heart rates and energy expenditures in
      Thai people. MATERIAL AND METHOD: This practice attracted researchers to study
      the benefits of the ASE in various groups. The ASE pattern was modified to swing
      forward 90 degrees and swing backward 60 degrees in this research study. The ASE
      was performed in three age groups of Thai people without diseases: 1) 18-25 years
      old, n = 25 2) 26-35 years old, n = 25 and 3) 36-55 years old, n = 25 sample of
      all cases were drawn from volunteers. The instrument utilized was heart rate
      monitor. Data was analyzed using descriptive statistics, t-test, ANO VA,
      correlation and multiple regression. RESULTS: The findings revealed that Thai
      people's mean heart rates, number of arm swings and energy expenditures were
      significantly different in each group at p-value = 0.05 (F = 5.757, 5.250 and
      3.196, p-value = 0.005, 0.007 and 0.47, respectively) with statistical
      significance at p-value = 0.05 in each group. The basic characteristics in the
      population groups found that body weight, age and number of arm swings affected
      heart rate (t = 2.5 75, 2.341 and 2.058, p-value = 0.012, 0.022 and 0.043,
      respectively). CONCLUSION: Although ASE is a light intensity exercise, if done 30
      minutes every day, ASE will improve efficacy of the cardiovascular system.

PMID- 26201139
TI  - "A misdirected media frenzy over killer nurse".

PMID- 26201140
TI  - England behind rest of UK on revalidation readiness.

PMID- 26201141
TI  - Regulator drops time limits for completing nurse education.

PMID- 26201142
TI  - English language test 'may harm' foreign recruitment.

PMID- 26201143
TI  - Young mental health service users vet nurses.

PMID- 26201144
TI  - Patients see no improvement in hospital nursing staff levels.

PMID- 26201145
TI  - Healthcare assistants renamed 'nursing assistants'.

PMID- 26201146
TI  - No system of nurse checks could 'prevent murder', says NMC chief.

PMID- 26201147
TI  - Midwife struck off for 'numerous failings' while at Morecambe Bay.

PMID- 26201148
TI  - Staff pressures jeopardise vital clinical research.

PMID- 26201149
TI  - Hunt clashes with RCN over out of hours pay and strike threats.

PMID- 26201150
TI  - "We must support Patients First Scotland to help whistleblowers".

PMID- 26201151
TI  - "Reviving clinical supervision is the key to high-quality care".

PMID- 26201152
TI  - Managing indwelling urinary catheters in adults.

PMID- 26201153
TI  - Options for users of intermittent catheters.
AB  - Users of intermittent self-catheterisation in the UK have access only to single
      use catheters. The Mult/Cath study is under way to determine whether multi-use
      catheters are safe and acceptable to patients; if so, a mixed approach could
      improve patient choice.

PMID- 26201154
TI  - Clinical supervision in a community setting.
AB  - Clinical supervision is a formal process of professional support, reflection and
      learning that contributes to individual development. First Community Health and
      Care is committed to providing clinical supervision to nurses and allied
      healthcare professionals to support the provision and maintenance of high-quality
      care. In 2012, we developed new guidelines for nurses and AHPs on supervision,
      incorporating a clinical supervision framework. This offers a range of options to
      staff so supervision accommodates variations in work settings and individual
      learning needs and styles.

PMID- 26201155
TI  - Managing constipation in older people in hospital.
AB  - Constipation is a distressing disorder that is common among older patients in
      hospital. It is often underdiagnosed and undertreated, and can lead to increased
      morbidity and prolonged hospital stays. In most cases this common problem can be
      treated successfully if the correct management plan is adopted. This article
      reviews the prevention and management strategies available to address the issue.

PMID- 26201156
TI  - Improving continence care around the world.
AB  - Global demographic trends suggest the incidence of both urinary and faecal
      incontinence will rise in the coming years, with significant health and economic
      costs for patients and healthcare services. Healthcare providers across the globe
      lack guidance on how to deliver the most efficient, patient-focused care. The key
      finding of a report drawn up to address this was that specialist nurses have an
      important role in initial assessment and treatment, supplanting doctor-led
      provision models. This can be achieved through accredited training.

PMID- 26201157
TI  - 60 seconds with Amy Pepper.

PMID- 26201158
TI  - Change from the outside in.

PMID- 26201159
TI  - [Cancer - just bad luck and unfortunate coincidence?].

PMID- 26201160
TI  - [What will change in 2015 in the realm of health and nursing?].

PMID- 26201161
TI  - [Heinrich Nestle Science Prize. For a good start in life].

PMID- 26201162
TI  - [The influence of a father with paraplegia on the psychosocial development of the
      children].

PMID- 26201163
TI  - [Implementation of development promoting care in neonatology from the viewpoint
      of the organizational consulting. 2].

PMID- 26201164
TI  - [The family friendly hospital - a give and take].

PMID- 26201165
TI  - [Green tea with lemon. Recommendations for healthy food combinations].

PMID- 26201166
TI  - [Over-ventilation and faulty nutrition of premature infants].

PMID- 26201167
TI  - [Finally implemented: child and youth service receives impartial dispute
      resolution / Hessian state government follows bpa demand for establishing a new
      arbitration board].

PMID- 26201168
TI  - The Polio Pioneers.

PMID- 26201169
TI  - Cyberbullying: a 21st Century Health Care Phenomenon.
AB  - This study examined bullying and cyberbullying prevalence among 367 adolescents
      10 to 18 years of age who were attending schools and community organizations in
      suburban and urban neighborhoods in the Midwest United States. The correlational
      design investigated adolescents' daily use of technology that could be used to
      cyberbully peers, such as cell phones, computers, email, and the Internet.
      Results showed that 30% of participants had been bullied during school, and 17%
      had been cyberbullied, with online social networking sites the most common media
      employed (68%). The majority of participants owned or had access to computers
      (92%), email accounts (88%), social networking accounts (e.g., Facebook or
      MySpace) (82%), and cell phones (79%). Daily technology use included an average
      of two hours on a computer and a median of 71 text messages per day. Logistic
      regression analysis revealed no significant differences in bullying or
      cyberbullying prevalence based on location (urban or suburban) or demographic
      characteristics. Given the substantial presence of cyberbullying and the increase
      in technology use among adolescents in the 21st century, nurses need knowledge of
      the phenomenon to plan assessments in clinical practice. Early identification and
      assessment of cyberbullying victims and perpetrators, and development and
      implementation of effective interventions are needed to reduce this form of
      bullying among adolescents.

PMID- 26201170
TI  - Correlates among Perceived Risk for Type 2 Diabetes Mellitus, Physical Activity,
      And Dietary Intake in Adolescents.
AB  - In the last two decades, the number of new cases of type 2 diabetes mellitus
      (T2DM) among U.S. adolescents has increased (Fagot-Campagna et al., 2000; SEARCH
      Study Group, 2006), which may be related to the lack of health-promoting
      behaviors, such as a balanced diet and adequate physical exercise. This
      descriptive correlational study examined the relationship between perceived risk
      for T2DM, dietary intake, and physical activity in adolescents (N = 80) 13 to 18
      years of age. The Children's Health Belief Model (Bush & lannotti, 1990) was the
      conceptual framework used for testing the theoretical relationships. Participants
      completed the following instruments: 1) Knowledge of Risk Factors for T2DM, 2)
      Health Beliefs for T2DM, 3) Godin-Shepard Leisure-Time Exercise Questionnaire
      (Godin & Shepard, 1997), and 4) the Demographic/Medical Questionnaire.
      Significant relationships were found between perceived risk, a subset of the
      Health Beliefs for T2DM scale, and the health promoting behaviors of dietary
      intake and physical activity. Implications for health-promoting nursing practice
      related to adolescent perception of risk and health-promoting behaviors of
      dietary intake and physical activity are addressed.

PMID- 26201171
TI  - Zolpidem and Sleep in Pediatric Burn Patients with Attention
      Deficit/Hyperactivity Disorder.
AB  - Existing research shows that hospitalized patients, especially pediatric burn
      patients, are often sleep deprived. A pre-existing diagnosis of attention
      deficit/hyperactivity disorder (ADHD) further compounds a burn patient's
      inability to sleep. This retrospective study compared the effectiveness of
      zolpidem on patients with acute burns with ADHD (n = 23) and patients with acute
      burns without ADHD (n = 23). Effectiveness was defined based on the need for a
      change in the sleep medication or an increase in the zolpidem dose during the
      first 12 days of treatment. This study found that sleep dysfunction was similar
      in pediatric burn patients with and without a concurrent diagnosis of ADHD.
      Sixteen (69.6%) patients with and 13 (56.5%) patients without ADHD required a
      sleep medication change (p = 0.541). Further, while patients with ADHD required a
      sleep medication change (median = 5 days) sooner than those without ADHD (median
      = 9 days), it appears that zolpidem is not an effective drug for managing sleep
      in pediatric burn patients with or without ADHD.

PMID- 26201172
TI  - Anger in Adolescent Communities: How Angry Are They?
AB  - Anger is a common factor in two causes of death in adolescence: homicide and
      suicide. This study looked at the level of anger in non-clinical convenience
      sample of adolescents (N = 139) between the ages of 12 and 19 years (early: 12 to
      14 years, mid: 15 to 16 years, late: 17 to 19 years) from a large Southeastern
      Baptist church. Participants completed the State-Trait Anger Expression
      Inventory, Beck and Children's Depression Inventories, and Children of Alcoholics
      Screening Test (CAST). The level of self-reported anger was low. The difference
      in anger between the three age groups was not statistically significant.
      Differences in gender were generally not significant statistically. A strong
      correlation exists between stress and anger. A minor relationship between
      parental drinking behaviors, as measured by the CAST, and anger was found. A
      significant relationship between anger and depression, and frequency of
      participation in religious activity and decreased anger was established. By
      increasing the current knowledge of anger in adolescents, it may be possible to
      gain insight into risk factors or triggers that cause anger. Interventions must
      be implemented early to prevent juvenile detention and to help adolescents remain
      in the community. Public policies addressing anger in adolescents are essential.
      Health care providers must work together to identify adolescents with disorders
      or feelings of isolation or disconnect and provide treatment based in communities
      so adolescents can still function and not be isolated. It is relevant that a
      mentor or someone that can be trusted is provided to build a safe and secure
      environment. This greater knowledge may aid in assessment and treatment of
      adolescents with dysfunctional anger.

PMID- 26201173
TI  - Diaper Need: A Change for Better Health.
AB  - Although diapers are essential for child health, nearly one in three American
      families cannot afford them (National Diaper Bank Network, 2013). A gap referred
      to as diaper need, the difference between the numbers of diapers infants require
      to stay clean and comfortable less the amount of diapers a family can afford
      without cutting back on other basic essentials, can have severe consequences for
      infants parents, and society. Within the context of the need for and economics of
      diapers, these severe consequences alert pediatric nurses to the impact they can
      have to bridge the diaper gap, thereby helping to alleviate diaper-related
      conditions and providing holistic, family-centered care.

PMID- 26201174
TI  - How Important Is a Conceptual Framework?

PMID- 26201175
TI  - Gluten-Related Disorders: Celiac Disease, Gluten Allergy, Non-Celiac Gluten
      Sensitivity.
AB  - Gluten is a protein complex found in the endosperm portion of wheat, rye, and
      barley. "Gluten-related disorder" is a term used to describe conditions related
      to ingestion of gluten-containing foods. Gluten has been implicated as the cause
      of a variety of gastrointestinal (GI) and extraintestinal symptoms. These
      symptoms are often non-specific and variable, making it difficult for the primary
      care provider to diagnose the cause and develop a management plan. Recently,
      gluten-related disorders have received much attention in the popular press, and
      the sale of gluten-free foods has become a multi-billion dollar business. It is
      important for pediatric primary care providers to understand the potential role
      of gluten in GI health and symptomatology so appropriate screening, diagnostic
      testing, and management can be provided.

PMID- 26201176
TI  - Parenthood and Professional Boundaries: Negotiating our Roles as
      Parent/Practitioners.

PMID- 26201177
TI  - [Multivariate analysis of pharyngo cutaneou fistulas after larynx cancer and
      lower pharynx cancer surgery].
AB  - OBJECTIVE: To investigate the relative factors of pharyngo cutaneou fistulas
      after larynx cancer and lower pharynx cancer surgery. METHOD: The clinical datas
      of 87 larynx cancer patients and lower pharynx cancer patients admitted were
      retrospectively analyzed. According to the type of postoperative complications
      all cases could be divided into pharyngo cutaneou fistulas group and no pharyngo
      cutaneou fistulas group. Thirty-eight kinds of factors,including age, clinical
      stage, plasma electrolytes level and type of procedure are in the multivariate
      analysis, and the variability indicators are in binary-regression analysis.
      RESULT: Eleven patients had pharyngo cutaneou fistulas (12.64%). Univariate
      analysis indicated that BMI, pre-operative serum potassium, operation time,
      cervical lymph dissection, post-operative prealbumin, post-operative hemoglobin,
      infection and delayed union of incision were the risk factors of pharyngo
      cutaneou fistulas (P < 0.05). Logistic stepwise regression analysis indicated
      that post-operative prealbumin and operation time were the independent risk
      factors. CONCLUSION: To avoid pharyngo cutaneou fistulam, it is very necessary to
      correct electrolyte disorder and negative nitrogen balance. To shorten the
      operation time, to avoid incision infection and delayed union were helpfulness,
      too.

PMID- 26201178
TI  - [Efficacy analysis of sequential surgery after the DCF scheme induction
      chemotherapy in T2-3 laryngeal carcinoma and hypopharyngeal carcinoma].
AB  - OBJECTIVE: To study clinical efficacy of surgery after the DCF induction
      chemotherapy in T2-3 laryngeal carcinoma and hypopharyngeal carcinoma. METHOD: To
      analyze clinical data about 102 cases of T2-3 laryngeal carcinoma and
      hypopharyngeal carcinoma retrospectively, 62 cases were divided into experimental
      group and 40 cases in control group, the experimental group completed three
      cycles of the DCF induction chemotherapy, then the efficacy was evaluated,
      surgery were carried out in the end, the control group received operation
      directly. In two groups, tumor response rates, toxicities, positive surgical
      margin rates and survival rate differences were observed and compared. RESULT:
      Tumor response rate was 61.3% in experimental group, the laryngeal carcinoma rate
      was significantly lower than that in hypopharyngeal (44.4% VS 84.6%, P < 0.05).
      Compared to its control, there were no significant differences about the positive
      surgical margin rate, the median survival time, 3-year and 5-year survival rate
      of laryngeal carcinoma(P > 0.05). The foci edges of 0. 3 cm and 0. 5 cm positive
      margin rate of hypopharyngeal carcinoma in experimental group were significantly
      lower than in its control (P < 0.05), but among the 1 cm edge' positive rate, the
      median survival time, 3-year and 5-year survival rate no significant differences
      were found (P > 0.05). During induction chemotherapy in the experimental group,
      no serious adverse reactions were found. CONCLUSION: Induction chemotherapy of
      DCF regimen can not only narrow T2-3 laryngeal carcinoma and hypopharyngeal
      carcinoma' area, but also ensure an adequate safety margin.

PMID- 26201179
TI  - [The application of double pedicle blood supply pectoralis major myocutaneous
      flap in reconstruction of laryngeal and hypo pharyngeal defect after carcinoma
      resection].
AB  - OBJECTIVE: To explore the application of double pedicle blood supply pectoralis
      major myocutaneous flap in reconstruction of laryngeal and hypo pharyngeal defect
      after carcinoma resection. METHOD: All the patients received initial treatment.
      Pectoralis major myocutaneous flap was Applied in one-stage reconstruction in 22
      cases of laryngocarcinoma and hypopharyngeal carcinoma with post-operation
      defect. During operation, pectoral branches of thoracoacromial vessels and branch
      of lateral thoracic vessels were reserved and prepared to be double pedicle
      vessel fascia bundle without muscle at the beginning part, rearched to defect
      area through subclavian tunnel. After operation, it is necessary to closely
      observe the subcutaneous swelling, quantity and color of the drain and others of
      neck surgery area to exclude the occurrence of surgical hematoma. When there is
      suspicion, do timely exploration. RESULT: Pectoralis major myocutaneous flaps of
      22 patients were all survived. Pharyngeal fistula occurred in 2 cases and was
      cured by change of dressing. Twenty-one cases received radiotherapy after
      operation without secondary flap necrosis. After follow-up of 6 months to 24
      months, one case of roll repairment of circumferential defect in cervical
      esophagus,found to have anastomotic stenosis 8 months after radiotherapy and then
      underwent gastrostomy treatment,the other 21 cases showed good recovery of
      swallowing function. Among 13 cases with laryngeal function reserved, only 1 case
      wearing tube and the extubation rate was 92.3% without communication barriers, no
      patient died in the short follow-up period. CONCLUSION: For double pedicle blood
      supply pectoralis major nyocutaneous flap, blood supply are fully guaranteed and
      does not require complicated equipment to observe and monitor the flap blood
      supply after operation, it is important to exclude factors that may lead to
      muscular flap necrosis to ensure the survival of pectoralis major myocutaneous
      flap.

PMID- 26201180
TI  - [The application of extended supraglottic horizontal partial laryngectomy in
      advanced laryngeal carcinoma and vallecula carcinoma].
AB  - OBJECTIVE: To discuss the function recovery and treatment effect of extended
      supraglottic orizontal-partial laryngectomy in the treatment of advanced
      laryngeal carcinoma and vallecula carcinoma. METHOD: Forty-four patients who
      received extended supraglottic orizontal partial laryngectomy were followed up on
      the survival, breath function, pronunciation and swallowing function. RESULT: The
      2-year, 3-year survival rates of this group were 72.7% and 71.4%, respectively.
      There were no recurrence cases in this group. All cases of death were due to
      cervical lymph node metastasis or recurrent cervical lymph node metastasis after
      cervical lymph node dissection. The extractive rate of tracheostomy tube was
      97.7%. Forty-two patients own good pronunciations. Two patients who received
      partial arytenoid cartilage resection own weaker pronunciations. After
      practising, all the patients can eat without the nasal feeding tube. CONCLUSION:
      Extended supraglottic orizontalpartial laryngectomy give complete resection of
      the primary lesion. Patients who received extended supraglottic orizontalpartial
      laryngectomy have good breath, swallowing and pronunciation function.

PMID- 26201181
TI  - [The MRI appearances of laryngeal carcinoma invading postcricoid area].
AB  - OBJECTIVE: By studying the MRI apperances of postcricoid area invaded by
      laryngeal carcinoma, to identify the characteristic appearances of the invaded
      postcricoid area and to provide information on the early detection of the
      lesions. METHOD: Eighteen cases of MRI images of postcricoid area invaded by
      laryngeal carcinoma were included in this study. To find out the characteristic
      manifestation of the lesions, the destructions of surrounding structures and
      layers, and the invaded extent were observed. RESULT: In 18 cases the invaded
      lesions of postcricoid area include the mucous layer, submucous fat layer and the
      mucous layer of anterior wall. In 14 cases the invaded lesions of postcricoid
      area include the mucous layer, submucous fat layer and the mucous layer of the
      posterior wall. The soft tissue mass was found in 15 cases, and disappeared
      hypopharynx cavity in 16 cases. In 14 cases, the full-thickness of both anterior
      and posterior walls were invaded, accompanied with soft tissue mass and
      disappeared hypopharynx cavity. CONCLUSION: The postcricoid area invaded by
      laryngeal carcinoma usually shows the destruction of normal structures, signal
      change in MRI and soft tissue mass. Being familiar with the imaging of the
      invaded postcricoid area is extremely important to early detect laryngeal
      carcinomas invading postcricoid area.

PMID- 26201182
TI  - [Therapeutic effect of submental flap in repairing of approaching circumferential
      defects after hypopharyngeal cancer ablation with laryngeal function
      unpreserved].
AB  - OBJECTIVE: To study the effectiveness of repairing nearly circumferential defect
      with the submental flaps after resection of laryngeal function unpreserved
      hypopharyngeal cancer. METHOD: All the cases were treated with the submental
      flaps after resection of hypopharyngeal cancer with laryngeal function
      unpreserved. RESULT: All 13 flaps were alive. Hypopharyngeal fistula occurred in
      2 cases. All patients had normal swallowing function. The patients were followed
      up 6-42 months. Of 13 cases,3 had recurrence at neck Lymph node, but no local
      hypopharyngeal recurrence was found. Seven cases were followed up more than 3
      years, and only 3 of them survived. CONCLUSION: Submental flap is an ideal tissue
      flap submental flap in repairing of approaching circumferential defects after
      hypopharyngeal cancer ablation with laryngeal function unpreserved for the
      repairment of after approaching circumferential defects after hypopharyngeal
      cancer ablation with laryngeal function unpreserved, For it is close to the
      defect region, safe, easy-to-obtain and easy-to-survive.

PMID- 26201183
TI  - [122 cases of endoscopic thyroidectomies through modified chest and mammary
      areola approach].
AB  - OBJECTIVE: To explore the safety and feasibility of endoscopic thyroidectomies
      through modified chest and mammary areola approach. METHOD: We retrospectively
      analyzed 122 cases of endoscopic thyroidectomies through a modified chest and
      mammary areola approach without extensive dissection of thoracic flap. The
      information about general status, surgical procedures and techniques,
      complications, etc. were summarized and discussed. RESULT: One hundred and twenty
      one cases were operated successfully while 1 case was converted to video-assisted
      thyroidectomy through infraclavicular approach. The maximum diameter of the mass
      was (2.05 +/- 1.06) cm, mean operation time was (88.61 +/- 27.87) min, the
      operative blood loss was (31.23 +/- 16.14) ml, duration of postoperative drainage
      was (3.54 +/- 0.88) d and overall drainage volume was (139.09 +/- 95.93) ml.
      Parathyroid glands were detected in specimens of 9 cases while no case of
      permanent postoperative hypocalcaemia was displayed. 6 cases of hoarseness were
      developed. One case experienced conversion surgery, all the others obtained
      satisfactory cosmetic result. All cases were followed up for 0-24 months without
      relapse and metastasis of the disease. CONCLUSION: Endoscopic thyroidectomy via a
      modified chest and breast areola approach can facilitated the procedure and avoid
      extensive dissection of thoracic flap, and proved to be safe and effective.

PMID- 26201184
TI  - [Correlative study of the metabolic disorder of hippocampus and cerebral cortex
      and cognitive impairment in moderate to severe OSAHS patients].
AB  - OBJECTIVE: To research the serum levels of BDNF, H2S and S-100beta as metabolic
      product of hippocampus and cerebral cortex in moderate to severe obstructive
      sleep apnea hypopnea syndrome(OSAHS) patients before and after surgery, and to
      analyze their correlations with cognitive impairment. METHOD: Forty-four randomly
      selected diagnosed OSAHS patients were divided into two groups according to
      Montreal Cognitive Assessment (MoCA), 19 cases in cognitively normal group and 25
      cases in cognitive dysfunction group. Cases in cognitive dysfunction group
      underwent UPPP oriented surgery, and received 6 months follow-up, 21 cases were
      remained as treament group, 4 cases lost. 19 cases of healthy subjects were
      randomly selected as the normal control group. All groups were detected for the
      serum BDNF, H2S and S-100beta levels to analyze the correlations between the
      biochemical indexes and sleep disorders indexes, hypoxia levels and cognitive
      function scores. RESULT: (1) In the comparison between the treatment group and
      the normal control group regarding PSG monitoring results, the AHI, I + II, LA/HT
      and SLT90% indexes of OSAHS patients increased, and the III + IV phase, REM
      phase, MSaO2 and LSaO2 decreased. In the comparison between the cognitive
      dysfunction group and the cognitively normal group, the III + IV, REM and LSaO2
      indexes of the cognitive dysfunction group decreased. (2) In the comparison
      between cognitive dysfunction group and cognitively normal group, and between the
      treatment group and the normal control group, BDNF and H2S levels increased and S
      100beta levels decreased, and the MoCA total scores, attention, memory/delayed
      recall scores decreased. (3) The correlation between biochemical indexes with PSG
      indexes was as follows. The serum BNDF and H2S levels were negatively correlated
      with AHI index. The serum BNDF and H2S levels were positively correlated with III
      + IV stage, REM stage and MSaO2 indexes. The S-100beta level was positively
      correlated with AHI index, and S-100beta levels were negatively correlated with
      III + IV stage, REM stage, MSaO2 and LSaO2 indexes. (4) The correlation between
      biochemical indexes and MoCA scores was as follows. The serum BNDF and H2S levels
      were positively correlated with MoCA total scores, attention, and memory/delayed
      recall scores. The serum S-100beta levels were negatively correlated with MoCA
      total scores, attention and memory/ delayed recall scores. (5) The linear
      regression equation between MoCA total scores in cognitive dysfunction group of
      OSAHS patients and the serum BNDF, H2S and S-100beta levels was as follows:
      Y(MoCA) = 40.131 + 0.22 X(BDNF) + 0.012 X(H2S)-0.647X(S-100beta) (R2 = 0.461).
      CONCLUSION: OSAHS patients with sleep disorder and nocturnal hypoxemia might
      suffer from cognitive dysfunction in which attention and memory predominates.
      Serum BNDF, H2S and S-100beta levels, which could indirectly reflect the
      metabolic abnormalities degree of hippocampus and cerebral cortex, are sensitive
      indicators of early cognitive dysfunction in OSAHS patients.

PMID- 26201185
TI  - [The standardized perioperative treatment of chronic rhinosinusitis with nasal
      polyps and asthma].
AB  - OBJECTIVE: To discuss the perioperative treatment of chronic rhinosinusitis with
      nasal polyps (CRSwNP) and asthma. METHOD: Retrospective analysis of perioperative
      clinical data of 43 cases with CRSwNP and asthma. The admitted and under
      endoscopic surgery. Patients with preventing perioperative asthma attacks and
      corresponding standardized treatment were Observed. RESULT: Thirty-five cases
      were stable during perioperative period and without asthma. Seven patients
      diagnosed as mild and moderate asthma attacks because of low pulse oximetry (SpO2
      92%-95%) and scattered wheeze heard in the lungs. So these patients were sent to
      ICU for the treatment. They went back to ward after their conditions turned to
      stable and no asthma during perioperative. One patient diagnosed as severe asthma
      attack, because irritability and suffocation happened, SpO2 decreased from 99% to
      84%-81%, diffuse wheeze could be heard in the whole lung . So we give him
      tracheal intubation and sent him to ICU for advanced treatment after breathing
      smooth. Five days later the patient retuned to the ward in stable condition and
      with no asthma attack again. CONCLUSION: Before operation the patients should be
      give some corresponding standardized comprehensive treatment according to the
      nasal symptoms and the degree of asthma attack, such as the application of
      topical steroid and antiallergic medicine. And some special treatment should be
      given to reduce airway hyperresponsiveness mucosa during anesthesia. These
      methods can reduce the risk of the asthma attacks and improve perioperative
      safety, prevent serious complications.

PMID- 26201186
TI  - [Application of coblation treatment via endoscopy in epiglottic benign tumors].
AB  - OBJECTIVE: To investigate the therapeutic effects of coblation treatment via
      endoscopy in epiglottic benign tumors. METHOD: Retrospective analysis was carried
      out in 128 patients with epiglottic benign tumors who underwent coblation
      treatment via endoscopy. The complications and therapeutic effect were analyzed.
      RESULT: The effective rate of treatment was 100% in cyst of epiglottis and in
      papillary epithelioma, and was 96.36% in hypertrophy of lingual tonsils. The
      pseudomembrane 1 w after operation. Postoperative pain is slight. There were no
      complications such as dyspnea, bleeding and infection. CONCLUSION: Radio
      frequency coblation via endoscopy will be applicable in the therapy of epiglottic
      benign tumors.

PMID- 26201187
TI  - [Study on the efficacy and safety of sublingual immunotherapy with standardized
      dermatophagoides farinae drops for allergic rhinitis].
AB  - OBJECTIVE: To evaluate the efficacy and safety of the sublingual immunotherapy
      with dermatophagoides farinae drops on patients with allergic rhinitis. METHOD:
      One hundred and twelve cases were collected from adult patients with dust-mite
      allergic rhinitis of our hospital who could adhere to treatment and regular
      follow-up. These patients were randomly allocated to receive either sublingual
      immunotherapy (SLIT group, n = 56) or medical treatment (Control group, n = 56).
      To evaluate the clinical efficacy by side effects which were registered, symptom
      and medication scores which were assessed and rhinoconjunctivitis quality of life
      questionnaire (RQLQ) which was completed in the baseline and two years after
      treatment. RESULT: Dropouts after the 2 years' treatment were 5 of SLIT group and
      4 of Control group respectively. SLIT group induced the significant reductions on
      both the symptom scores (7.81 +/- 3.14 to 3.89 +/- 2.01, P < 0.0 1) and the
      medication scores (2.86 +/- 0.75 to 0.44 +/- 0.06, P < 0.01). Meanwhile, Control
      group induced the reductions on both the symptom scores (8.01 +/- 3.32 to 5.20 +/
      2.43) and the medication scores (2.95 +/- 0.80 to 1.75 +/- 0.40). There were
      significant differences (P< 0. 01) in symptom and medication scores between the
      two groups after 2-year treatment. The patients in SLIT group had fewer symptoms
      and lower intake of medication. There were statistically significant differences
      in RQLQ between SLIT group [19 (15,22)] and Control group [36 (26,47)] after two
      years treatment (Z = -5. 21, P < 0.01). SLIT group also had significant
      improvement in RQLQ (Z = -6.10, P < 0.01) between before and after the treatment.
      There were 4 patients who showed adverse reactions in SLIT group (3 occurred in
      increment period, and 1 occurred in the maintenance period). The incidence of
      adverse reactions was 7.14%. No severe systemic side effects were registered.
      CONCLUSION: SLIT with standardized dermatophagoides farinae drops in China is
      safe and effective to patients with allergic rhinitis.

PMID- 26201188
TI  - [Ultrasound guided percutaneous microwave ablation in the treatment of recurrent
      thyroid nodules].
AB  - OBJECTIVE: To explore the clinical effect of ultrasound guided microwave ablation
      in the treatment 01 recurrent thyroid nodules. METHOD: Seventy-five cases of
      recurrent thyroid nodules were treated with ultrasound guided microwave
      ablation(MWA) under local anesthesia. All the patients underwent biopsy puncture,
      then the microwave ablation needle puncted in the center site of nodule with
      energy of 25-35 W, and the center tempera- ture could reach to 70-95  degrees C.
      RESULT: MWA were successfully performed in all the patients without significant
      com- plications. Temporary hoarseness occurred in 5 cases and dispeared after 1-3
      weeks, choking water occurred in 2 patients and recovered 3-5 days later.
      Ultrasound examination showed that the bloodstream of thyroid nodules disappeared
      in all the patients, and the nodules diminuted with varying degrees at 3-month
      and at 6-month follow- up Serum FT4 and TSH did not change significantly.
      CONCLUSION: Ultrasound guided MWA could be effective in the treatment of
      recurrent thyroid nodule with minimal invasive technology.

PMID- 26201189
TI  - [Meta-analysis on autogenous fat injection for unilateral vocal cord paralysis].
AB  - OBJECTIVE: This study conduct a qualitative synthesis and quantitative meta
      analysis of VFAFI, aimed to study whether it is a useful treatment for UVCP.
      METHOD: Electronic databases PubMed, YZ365. COM, WANFANG DATA, CMJD, CHKD,CNKI
      were searched using relevant keywords. Reported treatment outcomes were clustered
      into three categories,i. e. subjective, perceptual,acoustic,aerodynamic,and
      stroboscopic. Meta-analyses were performed on studies with numerical results
      using random effects model. RESULT: Five articles were identified with a total of
      404 patients. All the studies reported significant improvements or decrease after
      VFAFI in each category of outcome measurements. Meta-analysis demonstrated a
      significant increase or decrease in all categories. Adverse effects include
      slight inflammatory reponse can resolve spontaneously within 1 month. The
      recurrence rate after VFAFI was high due to the self absorption. NNE and Jitter
      of post-operation is lower than pre-operation,there is no significantly change
      between the control group and experimental group; F0, Shimmer and MPT of post
      operation is higher than pre-operation, there is no significantly change between
      the control group and experimental group. CONCLUSION: The invasiveness and
      morbidity of VFAFI are low and the side effects are self-limited. Meta-analyses
      demonstrated significant improvements or decreased from both objective and
      subjective measurements. Further controlled studies with longer follow-up periods
      and more person were included may evaluate the effectiveness of VFAFI more
      reliably.

PMID- 26201190
TI  - [Effect evaluation of allergen specific immunotherapy in patients with allergic
      rhinitis and asthma].
AB  - OBJECTIVE: To evaluate the effect of allergen specific immunotherapy (SIT) in
      patients with allergic rhinitis and asthma. METHOD A total of 68 patients with
      allergic rhinitis and asthma sensitized to dust mite were recruited into the
      study. They were randomly divided into two groups: SIT group n = 34 and
      symptomatic therapy (ST) group: n = 34. Patients in ST group received medication
      to treat, the symptoms, patients in SIT group received medication and 3 years of
      standardized allergen vaccine therapy. Evaluation index of therapy includes:
      rhinitis symptoms score, asthma symptoms score, drug score, skin prick test,
      serum specificity IgE (sIgE) , peripheral eosinophil (Eos) counting, lung
      function. The new sensitinogen rate was also assessed. RESULT: Clinical symptom
      scores, drug scores, lung function, blood eosinophil numbers and skin test result
      were all improved significantly after 3-year treatment in SIT group compared to
      those in ST group (P < 0.01). Although the level of serum slgE was
      decreased,there exited no statistic diferences between two groups. Only 8.8%
      patients have the new sensitization in SIT group, and 52.9% in ST group. There
      were no serious adverse reactions in treatment process. CONCLUSION: SIT for
      patients with AR and asthma can obtain excellent clinical efficacy.

PMID- 26201191
TI  - [Effect of Tiam 1 on cell proliferation and migration in head and neck squamous
      cell carcinoma cells].
AB  - OBJECTIVE: To investigate the effect of T lymphoma invasion and metastasis 1
      (Tiam 1) overexpression in head and neck squamous cell carcinoma (HNSCC) cells.
      METHOD: Endogenous expression of Tiam 1 in 8 head and neck squamous cell
      carcinoma cell (HNSCC) lines was investigated by real-time RT-PCR. A lentivirus
      vector containing Tiaml was transfected into UM-SCC-47 cells, a head and neck
      squamous cell carcinoma cell line with little endogenous Tiaml expression. Stable
      clone, obtained by G418 screening, were assayed by RT-PCR and Western blot to
      validate the gene expression efficiency. The biological behaviors of the
      transduced cells were determined by cell counting, MTT and in-vitro migration
      assay. RESULT: Tiam 1 gene was highly expressed in M2 cell line and it's low
      level expression was found in UM-SCC-47. Cell counting and MTT assay showed that
      over-expression of Tiaml significantly promoted cell proliferation (P < 0.05).
      The cell monolayers overexpressed Tiaml that resulted in a significant
      increasment of cell migration in infected head and neck squamous cell carcinoma
      cell lines (P < 0.05). CONCLUSION: Tiam 1 gene plays an important role in the
      growth and migration in head and neck squamous cell carcinoma cell lines. It may
      be a useful marker for metastasis of head and neck squamous cell carcinoma.

PMID- 26201192
TI  - [The research of apoptosis and proliferation inhibition of human laryngeal
      carcinoma cell line Hep-2 induced by Genistein].
AB  - OBJECTIVE: To investigate the effect of genistein on cell proliferation and
      apoptosis in human laryngeal carcinoma cell line Hep-2. METHOD: Cell Counting Kit
      8 (CCK-8) assay was used to measure the 50% inhibiting concentration (IC50) value
      of genistein; cell apoptosis rate and the distribution changes of cell cycle were
      determined with flow cytometry assay after treatment by gensitein. The
      morphological changes of tumor cells were evaluated by inverted phase contrast
      mircroscopy. RESULT: The IC50 of geniste responses to Hep-2 cells for 24 h was
      23.64 ug/ml. The apoptotic rates of Hep-2 cells treated by genistein for 24 h
      were 22.40% +/- 1. 65% (at 12 ug/ml genistein) and 30.64% +/- 2.94% (at 24 ug/ml
      genistein) respectively, significantly statistical differences were foundbetween
      above threated groups and the control group (P < 0.05); the apoptotic rates of
      Hep-2 cells treated by genistein for 48 h were 30.55% +/- 0.72%(at 12 ug/ml
      genistein) and 48.69% +/- 1.06% (at 24 ug/ml genistein) respectively,
      significantly statistical differences were found between above threated groups
      and the control group (P < 0.05). When Hep-2 cells exposed to the same
      concentration of genistein for 24 h, 48 h respectively, the difference in
      apoptotic rate was statistically significant. CONCLUSION: Genistein inhibited Hep
      2 cells growth obviously, meanwhile it could induced apoptosis of Hep-2 cells,
      the apoptotic rate was increasing with the increase of the time and dose of
      genistein.

PMID- 26201193
TI  - [Mechanism of apoptosis of nasopharyngeal carcinoma cells induced by
      polysaccharides extracts from Hedyotic diffusa].
AB  - OBJECTIVE: To explore the proliferation inhibition and apoptosis of
      polysaccharides extracts from polysaccharides extracts from Hedyotic diffusa
      (PEHD) on Human Nasopharyngeal Carcinoma (NPC)cell line CNE2 cells in vitro.
      METHOD: CNE2 cells treated with various concentrations of PEHD were detected by
      MTT assay at 24 h, 48 h, and 72 h. The apoptotic cells were analyzed by flow
      cytometry with Annexin V/PI staining. The expression levels of Bax, Bcl-2 and
      caspase-3 protein were examined by Western blotting method. RESULT: The growth of
      CNE2 cells were suppressed after treatment with PEHD (P < 0.05), MTT assay showed
      that the highest cell inhibition rate reached to 76.5%, the inhibition in the
      doses from 2 to 6 mg/ml showed dose-and-time-dependent. The percent of apoptosis
      in 4 and 6 mg/ml PEHD treatment groups for 48 h were 31.32%, 46.28%,
      respectively, and significantly higher than that in control groups, 4.86% (P <
      0.01). After the cells being treated with PEHD for 48 h, the expression of Bax
      and caspase-3 protein increased, and the expression of Bcl-2 protein decreased
      gradually. CONCLUSION: PEHD could inhibited the growth of CNE2 cells and was dose
      and-time-dependent, the mechanism may involve induction of cell apoptosis, which
      was associated with the activation of Bax and caspase-3 protein and the down
      regulation of Bcl-2 protein expression.

PMID- 26201195
TI  - [Clinical expericence of percutaneous dilational tracheostomy in 322 patients].

PMID- 26201194
TI  - [The relation between age and expression of Myosin VI and Disabled-2 in the
      cochlea of mice].
AB  - OBJECTIVE: To investigate the expression of Myosin VI and Disabled-2 (Dab2) in
      the cochlea of mice at different ages. METHOD: Forty KM mice were divided into
      four groups according to age, named as postnatal 2 week (P2w), P5w, P9w,
      P16month. The localization of protein in the basilar membrane of mice cochlea was
      detected by immunofluorescence staining and laser scanning confocal microscope
      (LSCM). The mRNA expression level of protein in cochlear at different ages was
      evaluated by real-time fluorescent quantitative reverse transcriptase-polymerase
      chain reaction (qRT-PCR). Statistical analysis was performed by the SPSS18.0
      software. RESULT: Myosin VI and Disabled-2 protein mainly expressed at the apical
      cytoplasm of hair cells. As for the inner hair cell, Dab2 labeling was abundant
      especially at the cuticular plate and nearby. Comparing four immunofluorescence
      staining images of Myosin VI, we found the fluorescence intensity of P2w and P16m
      were weaker than that of P5w and P9w. After setting P9w as the control group, qRT
      PCR revealed that the mRNA expression of MyosinVI and Dab2 in P2w was less than
      that in the control group (P < 0.01), while no significant difference was found
      between P5w and the control group, nor between P16m and the control group (P >
      0.05). CONCLUSION: Myosin VI and Dab2, two proteins which regulated the clathrin
      mediated endocytosis, expressed at hair cells of mice cochlea. In the inner hair
      cell, this process of endocytosis may be more efficient at the cuticular plate
      and nearby. The expression level of protein may change in different ages, and
      this probably leads to a difference of CME, it also may cause a defect of inner
      hair cells function.

PMID- 26201196
TI  - [Stepwise therapy and surgical indidation for chronic rhinosinusitis with septal
      deviation].

PMID- 26201197
TI  - [Clinicial analysis of 62 cases with maxillofacial and deep neck of space
      infection].

PMID- 26201198
TI  - [Application of nasal noninvasive continuous positive airway pressure in infants
      and young children weaning from postoperative mechanical ventilation after
      laryngocele surgery].

PMID- 26201199
TI  - [The pus cavity flushing and negative pressure drainage treatment on deep neck
      and upper mediastinal abscess].

PMID- 26201200
TI  - [One case of giant hypopharyngeal and esophageal inflammtory fibroid polyp].
AB  - The clinical manifestations of the disease include dysphagia, foreign body
      sensation in pharyngeal, retrosternal pain and regurgitation. Physical
      examination showed a sausage-shaped mass hanging outside the mouth, sometimes. CT
      scan demonstrated a benign placeholder in upper segment of esophagus. Surgery is
      the only way to achieve radical cure. Pathological examination: inflammtory
      fibroid polyp.

PMID- 26201201
TI  - [One case of pediatric obstructive sleep apnea hypopnea syndrome with pulmonary
      hypertension].
AB  - The clinical manifestation included snoring and mouth breathing for 2 years,
      repeated coughing and shortness of breath in action for more than 1 year.
      Physical examination of oral cavity showed tonsils were in grade III. The
      endoscopy showed 2/3 of postnaris were blocked by the adenoids. The preoperative
      ultrasonic cardiogram revealed the right atrial and right ventricular dilatation,
      pulmonary artery widened. The preoperative polysomnography (PSG) showed apnea
      hypopnea index (AHI) was 28.5 events an hour, and the lowest oxygen saturation
      (LSaO2) was 39%. The patient was diagnosed as severe obstructive sleep apnea
      hypopnea syndrome with pulmonary hypertension. The postoperative PSG showed the
      AHI was 11.7 events an hour, and the LSaO2 was 86%. The ultrasonic cardiogram at
      5 months after surgery didn't show any abnormalities.

PMID- 26201202
TI  - [Clinical analysis of nasal sinus mucocele with eye symptoms as main
      manifestation: 3 cases report].
AB  - Endoscopic sinus surgery is effective to nasal sinus mucocele with eye symptoms
      as main manifestation. It is very importment to raise the awareness of the
      disease and to prompt imaging examination. Three cases were reviewed. One
      mucocele was found in the frontal sinus ethmoid sinus,1 in the fronto-ethmoid
      sinus and 1 in the spheno-ethmoid sinus. All cases were preoperatively diagnosed
      by CT, MRI or intranasal endoscopy. Nasal sinus mucocele with eye symptoms as
      main manifestation should be early diagnosed. Endoscopic sinus surgery is a safe
      and effective method for the treatment of nasal sinus mucocele,and could be the
      primary choice for it. All cases were treated by nasal endoscopic sinus surgery.
      The majority of symptoms, such as exophthalmos, epiphora and diplopia,
      disappeared in all patients. However, vision recovery was observed only in some
      patients.

PMID- 26201203
TI  - [The migrating pharyngeal foreign body resulted in cervical mass: one case
      report].
AB  - Pharyngeal foreign body is a common disease. The diagnosis and treatment are
      easy. However, in a few cases, pharyngeal foreign bodies migrated to other part
      of body, which often causing missed diagnosis or misdiagnose to delaythe
      treatment, and even lead to fatal complications. Here we present a case report of
      a 52-year-old female patient.who was found to have cervical mass 20 days before.
      Contrast-enhanced computed tomography showd a foreign body and foreign body
      granuloma on the left side of the neck. To look back on the history, the patient
      swallowed a fish bone in mistake one month ago.

PMID- 26201204
TI  - [Left laryngopharyngeal rhabdomyoma: one case report].
AB  - The male patient was 72 years old with 10-years hoarseness. Electronic
      laryngoscopy showed a great pink lobulated lesion at the left back of soft palate
      and lateral pharyngeal wall, close to the choanal region. Neck CT revealed
      irregular signal intensities of soft tissue at the left wall of nasopharynx, side
      wall and posterior wall of oropharynx and hypopharynx, bilateral submandibular
      and glottic region. The patient underwent operation treatment. Histopathology
      showed the mass was composed of identical mature rhabdomyoma cells, with scarce
      interstitial substance. The tumor cells was round, oval or polygonal with
      eosinophilic cytoplasmic granules, longitudinal grain or grain was occasionally
      found. Some tumor cells arranged in disorder with match structure. Pathological
      diagnosis was rhabdomyoma.

PMID- 26201205
TI  - [Advancement biological target therapy of nasopharyngeal carcinoma].
AB  - Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumor in
      China, Southeast Asia and North Africa region. The main treatment of NPC is
      radiation therapy, and concurrent chemoradiotherapy has become the standard
      treatment for locally advanced NPC Up to date, the targeted therapy in NPC has
      been gradually appreciated recently, in this paper, NPC biological targeted
      therapy in recent years as a progress of treatment were reviewed.

PMID- 26201206
TI  - [Studies progress in preventing xerostomia after radiotherapy of nasopharyngeal
      carcinoma].
AB  - Radiotherapy is the main way to treat the Nasopharyngeal Carcinoma. But there are
      a lot of serious complications, the most common one of then is radioactive
      xerostomia. It seriously affect the patients's quality of life, even make
      patients change or stop their radiotherapy. It is extremely important to prevent
      and treat xerostomia caused by radiotherapy.

PMID- 26201207
TI  - Care without Judgment?

PMID- 26201208
TI  - Impact of Palliative Care Consultations on Resource Utilization in the Final 48
      to 72 Hours of Life at an Acute Care Hospital in Ontario, Canada.
AB  - A wealth of literature and economic analyses has shown that palliative care is
      associated with significant cost reductions compared to nonpalliative care.
      However, no one has assessed the impact of an inpatient palliative care
      consultation service on costs at the very end of life (48 to 72 hours before
      death). This retrospective cohort review of 100 inpatients at a large hospital in
      Ontario examines the effect of palliative care consultations on seven independent
      cost categories during this period: medical-imaging costs, physician costs,
      laboratory costs, pharmaceutical costs, other health professional costs, food
      services costs, and unit costs. Our study shows that patients who receive
      palliative care consultations are associated with significantly lower costs in
      the final 48 to 72 hours of life than their nonpalliative counterparts. Another
      significant finding was that the degree of cost reduction at the very end of life
      appears to be relative to how soon after the patient's admission the palliative
      care consultation was initiated.

PMID- 26201209
TI  - Predictors of Place of Death for Those in Receipt of Home-Based Palliative Care
      Services in Ontario, Canada.
AB  - Many cancer patients die in institutional settings despite their preference to
      die at home. A longitudinal, prospective cohort study was conducted to
      comprehensively assess the determinants of home death for patients receiving home
      based palliative care. Data collected from biweekly telephone interviews with
      caregivers (n = 302) and program databases were entered into a multivariate
      logistic model. Patients with high nursing costs (odds ratio [OR]: 4.3;
      confidence interval [CI]: 1.8-10.2) and patients with high personal support
      worker costs (OR: 2.3; CI: 1.1-4.5) were more likely to die at home than those
      with low costs. Patients who lived alone were less likely to die at home than
      those who cohabitated (OR: 0.4; CI: 0.2-0.8), and those with a high propensity
      for a home-death preference were more likely to die at home than those with a low
      propensity (OR: 5.8; CI: 1.1-31.3). An understanding of the predictors of place
      of death may contribute to the development of effective interventions that
      support home death.

PMID- 26201210
TI  - Barriers to, and Facilitators of Physical Activity in Patients Receiving
      Chemotherapy for Lung Cancer: An exploratory study.
AB  - AIM: Physical activity (PA) has a positive effect on the cardiorespiratory
      fitness, lung cancer symptoms, and quality of life of lung cancer patients. The
      aim of our study was to identify barriers to, and facilitators of PA in lung
      cancer patients. METHODS: We collected data from five patients diagnosed with
      primary, advanced non-small-cell lung cancer (NSCLC) who were receiving
      chemotherapy. Choosing a qualitative approach, we conducted an exploratory
      analysis using the thematic analysis technique to process the data. RESULTS:
      Seven barriers to, and facilitators of PA were identified and grouped into four
      categories. We found that psychological and social factors affect patients'
      willingness and ability to engage in PA, while physiological and environmental
      factors have an impact on the duration, intensity, and regularity of their PA.
      CONCLUSION: Our study highlighted some of the effects that the barriers to PA
      have on the practice of it in our patient group. Our findings may be used by
      professionals to design adapted PA programs.

PMID- 26201211
TI  - Caring for Brain Tumour Patients: Psychological reactions after bereavement.
AB  - AIM: The aim of this study was to describe the changes in quality of life and in
      levels of anxiety and depression experienced by caregivers of patients with brain
      tumour 18 months after their bereavement. METHODS: This longitudinal study
      employed data from two time points: time 1, during the hospital stay of the
      caregiver's loved one; and time 2, approximately 18 months after the death of the
      patient. A total of 51 caregivers agreed to participate in the study at both time
      points. We used the Hospital Anxiety and Depression Scale and the 36-Item Short
      Form Health Survey; we compared the data obtained at the two time points using
      the paired-samples t-test. RESULTS: Caring for someone with a brain tumour had a
      greater impact on the caregivers' mental health than on their physical well
      being. At time 2, the caregivers' levels of anxiety and depression and
      psychological burden were decreased, indicating that they were in a better
      emotional state than they had been in time 1. However, the mean values in the
      depression, vitality, and mental health subscales were lower than those in the
      normative data, indicating that these caregivers had a worse psychological status
      than members of the normative group. CONCLUSION: Our study underscores the
      necessity of supporting caregivers and monitoring their suffering levels; such
      suffering can compromise their social and work lives, not only during the disease
      trajectory but also in bereavement. Providing psychological and emotional support
      for caregivers of patients with brain tumour during both periods could lessen the
      suffering and unhappiness of these caregivers.

PMID- 26201212
TI  - The Role of Heart Rate Variability in Advanced Non-Small-Cell Lung Cancer
      Patients.
AB  - AIM: Several recent studies have suggested that assessing heart rate variability
      (HRV) is an easy method for obtaining prognostic information on cancer patients;
      however, these studies had limitations such as uncontrolled confounders and small
      numbers in a heterogeneous group. The intention of our study was to explore and
      validate the role of HRV variables in patients with advanced non-small-cell lung
      cancer (NSCLC). METHOD: A total of 167 patients who were eligible for HRV testing
      were consecutively enrolled from a regional hospital in South Korea. Demographic
      and clinical variables, including the Eastern Cooperative Oncology Group (ECOG)
      performance status grade, NSCLC stage, therapeutic intervention, and other data
      were also recorded. The effects of time-domain and frequency-domain indices of
      HRV were compared with other clinical factors to determine overall survival.
      RESULTS: Among the HRV parameters, standard deviation of all normal-to-normal
      intervals (SDNN) significantly predicted poor survival by univariate analysis.
      However, multivariate analysis revealed that it was not an independent
      prognosticator for survival in NSCLC patients, as the HRV parameters
      significantly correlated with the ECOG performance status grade. CONCLUSION: HRV
      variables should be used to monitor advanced NSCLC patients' general well-being
      and ability to perform the activities of daily living rather than to predict
      their overall survival.

PMID- 26201213
TI  - Palliative Care Information Needs in Central and Eastern Europe and the
      Commonwealth of Independent States.
AB  - In a cross-national survey, we examined the information needs and barriers to
      accessing palliative care information in Central and Eastern Europe (CEE) and the
      Commonwealth of Independent States (CIS). In total, 584 healthcare professionals
      from 22 countries completed the questionnaire. Information on legislation and
      official papers (67 percent) and information on education courses in palliative
      care (65 percent) were the most frequently reported information needs. Major
      barriers to accessing palliative care information were language and a lack of
      easily accessible and affordable, clinically relevant information. An informative
      Web site, an electronic newsletter, and regular meetings or conferences were
      rated as the most important information channels. We concluded that access to
      reliable and well-structured information should be facilitated for healthcare
      professionals in CEE and CIS countries to assist them in their clinical decision
      making. Most importantly, more in-depth qualitative research and dialogue with
      stakeholders in the different countries are needed to develop context-specific,
      tailor-made strategies.

PMID- 26201214
TI  - What Diagnostic Tools Exist for the Early Identification of Palliative Care
      Patients in General Practice? A systematic review.

PMID- 26201215
TI  - Methylnaltrexone to Palliate Pruritus in Terminal Hepatic Disease.

PMID- 26201216
TI  - [Gypsy moth Lymantria dispar L. in the South Urals: Patterns in population
      dynamics and modelling].
AB  - The analysis is conducted on population dynamics of gypsy moth from different
      habitats of the South Urals. The pattern of cyclic changes in population density
      is examined, the assessment of temporal conjugation in time series of gypsy moth
      population dynamics from separate habitats of the South Urals is carried out, the
      relationships between population density and weather conditions are studied.
      Based on the results obtained, a statistical model of gypsy moth population
      dynamics in the South Urals is designed, and estimations are given of regulatory
      and modifying factors effects on the population dynamics.

PMID- 26201217
TI  - [Selective feeding in fish: Effect of feeding and defensive motivations evoked by
      natural odors].
AB  - The effect of feeding and defensive motivations evoked by natural olfactory
      signals (the food odor, the alarm pheromone) on choice and consumption of food
      items different in color and taste, and the manifestation of foraging behavior
      were examined in fish (koi Cyprinus carpio, roach Rutilus rutilus). The agar-agar
      pellets of red and green color having one of the amino acids (glycine, L-proline,
      L-alanine; all in concentration of 0.1 M) were simultaneously offered to single
      fishes in pure water, and in water extract of Chironomidae larvae or in water
      extract of fish skin. It was found out that odors used have different effects on
      fish foraging activity and on pellet selection for both pellet choice and
      consumption. On background of food odor, fish grasped pellets more often than in
      pure water. The equal choice of red and green pellets in pure water shifted to
      the preference of red ones in the presence of food odor. Despite the increase in
      the absolute number of pellets grasped, the relative consumption reduced and was
      replaced by selective consumption of pellets with glycine regardless of their
      color. Increasing demand for the food quality, due to the increased feeding
      motivation in response to food odor, is an important adaptation enhancing
      selection and consumption of food with more appropriate sensory qualities for
      fish. Defensive motivation caused by alarm pheromone suppressed predisposition.
      of fish to feed. Fish grasped pellets several times less often than in pure water
      and refused most of them. Any changes in the color or taste preferences were
      absent. Feeding behavior of fish of both species was characterized by repeated
      intraoral pellet testing, but in koi handling was less typical than in roach. In
      both species, handling activity was higher in those cases when the pellet was
      finally rejected. This activity was enhanced also on the background of food odor.

PMID- 26201218
TI  - [Relationship between characteristics of sexual behavior and male sperm
      competitive ability in taxa of superspecies complex Mus musculus sensu lato].
AB  - Some physiological parameters that determine quality of male sperm (its
      concentration, spermatozoa morphology) and testicle size vary in integrity, i.e.
      the bigger are testicles the higher is sperm quality. Therefore, the estimate of
      testicles relative mass is often used as a characteristic of sperm competitive
      ability when comparing phylogenetically close mammal species. In house mice
      belonging to the superspecies complex Mus musculus s.l., testicles relative mass
      is greater in exoanthropic species than in synanthropic ones. It is shown in our
      study that this pattern is apparent also at the intraspecies level since
      testicles mass index, sperm concentration, and percentage of morphologically
      normal spermatozoa in subspecies Mus musculus wagneri, which is facultatively
      synanthropic, are higher compared with synanthropic subspecies M m. musculus. An
      analysis of sexual behavior of the three forms (namely, exoanthropic species M.
      spicilegus and two subspecies mentioned above) indicates that in M. spicilegus
      both sexual behavior efficiency and ejaculation rate during coupling were higher
      as compared with other two subspecies. Based on the analysis of life pattern,
      reproduction systems, and group spatial-ethological structure, the hypotheses are
      formulated that explain the maintenance of selection directed to increase of
      sperm competitive ability in exoanthropic house mice species.

PMID- 26201219
TI  - [Influence of photosynthetic parameters on leaf longevity].
AB  - Higher plants show a wide range of leaf lifespan (LL) variability. LL is
      calculated as a sum of functional LL(f) (corresponding to the time of active
      photosynthesis and CO2 accumulation in the leaf) and nonfunctional LL(n) (the
      time of photosynthetic activity absence). For evergreen species of boreal zones,
      LL(n) corresponds to the period of winter rest. Photosynthetic potential of leaf
      (PPL), interpreted as the maximum possible amount of CO2 that can be fixed during
      its life, can be estimated on the basis of maximum photosynthesis rate (P(a))
      dynamics during LL(f); the maximum (P(a max)) being achieved in mature leaf.
      Photosynthetic potential depends on LL(f) more strongly than on P(a max). The
      PPL/LL(f) ratio is indicative of the rate of PPL realization over leaf lifespan.
      As LL(f) shows strong positive correlation with LL, the latter parameter can also
      characterize the rate of PPL realization. Long LL(f) in evergreen species
      provides higher PPL, which is advantageous by comparison with deciduous ones. In
      evergreen species, the PPL itself is realized slower than in deciduous ones. The
      increase in LL(f) and LL is accompanied by the increase in leaf constructional
      cost (LCC(a)) as well as the decrease in photosynthesis rate. At that,
      photosynthesis rate per unit of dry weight (P(m)) decreases much faster than that
      per unit of leaf area (P(a)). Apparently, when considering dry leaf weight, the
      apoplast share seems to be much higher in long-living leaves of evergreen species
      than in short-living leaves of deciduous species. The leaf payback (LP) may be
      stabilized by unidirectional shifts in PPL and LCC(a). Species with short/long
      LL(f) and high/low PPL realization rate are typical for early/late succession
      stages and for habitats with the environmental conditions favorable/adverse for
      photosynthesis and growth. If the conditions for photosynthesis and growth are
      favorable, high PPL realization rate provides advantage in competition. The PPL
      realization rate is coupled with the rate of leaf senescence.

PMID- 26201220
TI  - [The contribution of L.G. Ramensky theoretical legacy to modern vegetation
      science (to the 130 anniversary of the scientist's birth)].
AB  - L.G. Ramensky (1884-1953) was an outstanding Soviet geobotanist of the first part
      of XX century. Considered is his theoretical legacy and its contribution to
      modern vegetation science. L.G. Ramensky formulated the principle of vegetation
      continuum based on which the modern paradigm of vegetation science has been put
      into shape. The scientist made a contribution to the development of such
      important theoretical conceptions as types of plant strategy, coenosis and
      coenobiosis (coexistence of species), patterns of interannual variability in
      plant communities, ecological successions. The unique ecological scales were
      established by L.G. Ramensky that characterize the distribution of 1400 species
      over the gradients of soil moistening, richness, and salinization as well as
      moistening variability, pastoral digression, and alluvial intensity. He came out
      against mechanistic notions by V.N. Sukachev on a biogeocoenosis structure. The
      scientist did not offer his own method of plant communities classification but
      his well-reasoned criticism of dominant classification played a great role in
      adoption of floristical classification principles (Braun-Blanquet approach) by
      phytocenology in our country.

PMID- 26201221
TI  - Effect of polymer-based desensitizer with sodium fluoride on prevention of root
      dentin demineralization.
AB  - PURPOSE: To evaluate the effect of a fluoride-containing polymer-based
      desensitizer on prevention of root demineralization using micro-computed
      tomography (micro-CT). METHODS: Bovine root dentin blocks were divided into four
      groups; no treatment (Control); 1% oxalic acid (OA); MS Coat One containing
      methacrylate-co-p-styrene sulfonic acid (MS polymer) and 1% oxalic acid (MSO);
      and MS Coat F containing MS polymer, 1% oxalic acid and 3,000 ppm sodium fluoride
      (MSF). A window of the dentin surface was treated with each solution. The blocks
      were scanned using micro-CT after demineralization (pH 4.5, 5 hours). The dentin
      surfaces before and after demineralization were examined by scanning electron
      microscopy (SEM). Fluoride ion release was measured using a fluoride ion-specific
      electrode. The data were statistically analyzed using one-way ANOVA and Tukey's
      test (alpha = 0.05). RESULTS: MSF showed the lowest mineral loss (3176.5 +/-
      630.5 vol%MUm), which was significantly different from Control (4600.1 +/- 1053.4
      vol%MUm), OA (3992.7 +/- 899.0 vol%MUm) and MSO (3900.2 +/- 645.4 vol%MUm).
      [corrected]. Under the SEM observations, the dentin tubules appeared to be
      blocked after all desensitizer treatments. After demineralization, the exposure
      of dentin tubules was clearer in OA and MSO compared to MSF which showed sealed
      dentin tubules after demineralization. Fluoride ion release was detected only in
      the MSF group.

PMID- 26201222
TI  - The dentin tubule occlusion effects of desensitizing agents and the stability
      against acids and brushing challenges.
AB  - PURPOSE: To investigate the effects of desensitizing agents on dentin tubule
      occlusion, acid and tooth brushing challenge, and microhardness change of human
      dentin. METHODS: Partially demineralized dentin slabs were divided into four
      groups (n = 30): (1) Control, (2) Non-desensitizing toothpaste, (3) Pro-Argin
      toothpaste, (4) CPP-ACP paste. The specimens were treated with these dentifrices
      for 2 minutes/day and soaked in artificial saliva (AS) for 24-hour
      remineralization. Then the dentin discs were divided into three subgroups for
      removal resistance tests: acid challenge, mechanical brushing challenge and blank
      control. Changes in dentin morphology were observed using scanning electron
      microscopy (SEM). Vickers microhardness measurements were performed at baseline
      and after 24-hour remineralization for all groups. RESULTS: A surface layer and
      intra-tubular crystals were observed in SEM imaging of Pro-Argin toothpaste and
      CPP-ACP paste groups, which occluded most of the dentin tubules for those
      specimens. But the dentin tubules were opened after the acid challenge again.
      Moreover, the dentin microhardness showed a slight increase after 24-hour AS
      immersion. The percentage microhardness gain (PMG) values of these two groups
      were 5.4% and 5.1% respectively, which were significantly higher than the other
      groups (P < 0.05).

PMID- 26201223
TI  - Serum lipid levels in patients with minor recurrent aphthous ulcers.
AB  - PURPOSE: To evaluate the possible association between minor recurrent aphthous
      ulcers (RAUs) and plasma lipid levels. METHODS: 85 patients (50 female, 35 male)
      with minor RAUs and another 80 patients (52 female, 28 male) without minor RAUs
      were included in the study. Body mass index (BMI), hemoglobin (HB), white blood
      cells (WBCs), platelets (PLT), glucose (GL), total cholesterol (TCH),
      triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL),
      creatinine (CR), alanine transaminase (ALT), and aspartate transaminase (AST)
      levels, as well as the gender and age of the patients in the groups were
      compared. RESULTS: Cumulative evaluation showed that HDL was statistically higher
      in the control group (P < 0.05). Except for WBCs, PLT, TG, and ALT, all
      parameters were significantly higher in the study group (P < 0.05). Correlations
      between minor RAUs and investigated parameters were observed with age, BMI, HB,
      GL, CR, TCH, HDL, LDL, and AST (P < 0.05). If gender was considered and the
      groups were compared, the greatest differences were seen between the female study
      group and the female control group (age, BMI, HB, GL, CR, TCH, TG, LDL, ALT; P <
      0.05). Correlations were mostly observed between minor RAUs and parameters within
      the female group (P < 0.05).

PMID- 26201224
TI  - Clinical and microbiological efficacy of systemic roxithromycin as an adjunct to
      non-surgical periodontal therapy in treatment of chronic periodontitis. A
      randomized, double-blinded, placebo-controlled clinical trial.
AB  - PURPOSE: The objective of this randomized clinical trial was to evaluate the
      clinical and microbiological effects of systemic administration of roxithromycin
      (RXM) as an adjunct to non-surgical periodontal therapy (NSPT) in the treatment
      of individuals with moderate to severe chronic periodontitis (CP). METHODS: 70
      individuals (38 males and 32 females, aged 25 to 60 years) with moderate to
      severe CP were randomly allocated into two groups. 35 individuals were allocated
      to full mouth SRP+RXM while 35 individuals were allocated to SRP+ Placebo group.
      The clinical parameters evaluated were probing depth (PD), clinical attachment
      level (CAL), gingival index (GI), plaque index (PI) and % bleeding on probing
      sites (%BOP) at baseline (B/L), 1-, 3- and 6-month intervals while microbiologic
      parameters included percentage of sites positive for periodontopathic bacteria A.
      actinomycetemcomitans, P. gingivalis and T. forsythia at B/L, 3 and 6 months
      using polymerase chain reaction. RESULTs: Both groups showed improved clinical
      and microbiologic parameters over 6 months. RXM group showed a statistically
      significant reduction in mean PD and CAL gain as compared to the placebo group (P
      < 0.0001). There was reduction in percentage of sites positive for
      periodontopathic bacteria over the duration of the study in both groups and a
      statistically significant reduction in the number of sites positive for A.
      actinomycetemcomitans in RXM group (P < 0.001).

PMID- 26201225
TI  - Strengthening effect of horizontally placed fiberglass posts in endodontically
      treated teeth restored with direct resin composite.
AB  - PURPOSE: To assess the fracture strength of cavity preparations, directly
      restored with resin composite, with and without the presence of fiberglass posts
      with different diameters. METHODS: 84 extracted third molars were embedded in
      acrylic resin and divided into six groups (n = 14 per group): healthy (H); cavity
      preparation (P); cavity preparation + endodontic treatment (PE); PE + resin
      composite (R); PE + R + 2 horizontally transfixed fiberglass posts 1.1 mm in
      diameter (PERP1); PE + R + 2 fiberglass posts 1.5 mm in diameter (PERP2). The MOD
      cavity preparations were standardized with their width corresponding to 2/3 of
      the buccolingual distance and occlusogingival depth of 4 mm, with 2 mm remaining
      above the cemento-enamel junction. Endodontic treatments were performed in the
      PE, R, PERP1 and PERP2 groups. The buccal surface received two demarcations to
      create orifices for placement of the PERP1 and PERP2 posts. Once the fiberglass
      posts were placed, the teeth were restored with resin composite. In group R, only
      resin composite was used. After 24 hours, the teeth were subjected to the
      fracture toughness test on a universal testing machine. A 10 KN load cell and
      crosshead speed of 1 mm/minute was used until fracture occurred. After testing,
      the teeth were inspected for the type of fracture classified as: pulpal floor
      fracture (AP) or cuspal fracture (CP). RESULTS: The data were subjected to ANOVA
      and Tukey's test (P < 0.05%), demonstrating a statistical difference between
      groups: H 3830NA; P 778ND; PE 572.93ND; R 1782NC; PERP1 2988NB; PERP2 3100NAB.
      The fracture pattern was similar between the tested groups, showing 50% of
      fracture for cusps and pulpal floor.

PMID- 26201226
TI  - Effects of short-term immersion and brushing with different denture cleansers on
      the roughness, hardness, and color of two types of acrylic resin.
AB  - PURPOSE: To investigate the cumulative effects of brushing (B) or immersion (I),
      using different cleansing agents, on the surface roughness, hardness and color
      stability of a heat-polymerized denture resin, Lucitone 550 (L), and a hard
      chairside reline resin, Tokuyama Rebase Fast II (T). METHODS: A total of 316
      specimens (10 x 2 mm) were fabricated. The specimens (n = 9) were divided into
      brushing or immersion groups according to the following agents:
      dentifrice/distilled water (D), 1% sodium hypochlorite (NaOCl), Corega Tabs (Pb),
      1% chlorhexidine gluconate (Chx), and 0.2% peracetic acid (Ac). Brushing and
      immersion were tested independently. Assays were performed after 1, 3, 21, 45 and
      90 brushing cycles or immersion of 10 seconds each. Data were evaluated
      statistically by repeated measures ANOVA. Tukey's honestly significant difference
      (HSD) post-hoc test was used to determine differences between means (alpha =
      0.05). RESULTS: For L there was no statistically significant difference in
      roughness, except a significant decrease in roughness by brushing with D. T
      showed a significant effect on the roughness after 90 immersions with Ac.
      Hardness values decreased for L when specimens were immersed or brushed in NaOCl
      and Pb. The hardness of T decreased with increases in the repetitions (immersion
      or brushing), regardless of the cleaning method. Values of color stability for L
      resin showed significant color change after brushing with and immersion in Ac and
      Pb. Brushing with D exhibited a higher incidence of color change. For T there
      were no significant differences between cleaning agents and repetitions in
      immersion. A color change was noted after three brushings with the Ac, Chx, and
      D. Brushing with dentifrice decreased roughness of L. Immersion in or brushing
      with NaOCl and Pb decreased the hardness of L. For T, hardness decreased with
      increases in immersions or brushing. Color changes after the immersion in or
      brushing with cleaning agents were clinically acceptable according to National
      Bureau of Standards parameters for both resins.

PMID- 26201227
TI  - Class I restoration margin quality in direct resin composites: A double-blind
      randomized controlled clinical trial.
AB  - PURPOSE: To evaluate the margin quality of direct resin composite restorations
      comparing the enamel-dentin adhesive standard procedure with additional use of
      adhesive layer at the external outline. METHODS: A total of 648 teeth with Class
      I occlusal lesions in molars and premolars were randomly selected and distributed
      into two groups of 324 each in order to compare the margin quality with two
      restoration strategies. Lesions were sealed with the standard adhesion procedure
      for direct resin composite restorations (Group 1) and with an additional
      procedure of enamel adhesive on the outer boundary of the finished restoration
      (Group 2). Evaluation of marginal quality at 6, 12, 24, 36 and 48 months was
      performed and described as good marginal adaption or as poor quality defined as
      Inadequacy A (IA): overhanging resin or change of color; Inadequacy B (IB): the
      presence of a gap at the enamel-composite interface that retained the probe tip;
      or Inadequacy C (IC) presence of gap at the enamel-composite interface with
      explorer tip penetration of more than 1 mm. RESULTS: Data showed a higher number
      of Inadequacy A for restorations with the additional technique for marginal seal
      (Group 2): 16 of 24 total (57%) at 6 months; 28 of 37 total (76%) at 12 months;
      36 of 44 total (82%) at 18 months; 22 of 33 total (67%) at 24 months; 14 of 21
      total (70%) at 36 months and 16 of 25 total (64%) at 48 months. The Inadequacy B
      and C of marginal seal were more prevalent for restorations without the
      additional marginal seal (Group 1): 18 of 28 total (64%) at 12 months with
      inadequacy B; 19 of 25 total (76%) with inadequacy B and 16 total (100%) with
      inadequacy C at 18 months; 9 of 17 total (53%) with Inadequacy B and 13 total
      (100%) with Inadequacy C at 24 months; 12 of 17 total (70%) with Inadequacy B and
      9 of 13 total (73%) with Inadequacy C at 36 months; 14 of 24 total (58%) with
      Inadequacy B and 7 of 11 total (63%) with Inadequacy C at 48 months.

PMID- 26201228
TI  - Mechanical properties and ultrastructural characteristics of a glass fiber
      reinforced composite.
AB  - PURPOSE: To examine the ultrastructural characteristics of a fiber-reinforced
      composite (FRC) and its behavior in vitro as a framework for fixed partial
      dentures (FPDs). METHODS: A total of 40 specimens were prepared using extracted
      teeth fixed in methacrylate blocks as supports for the FPD, then the specimens
      were divided into four groups depending on whether a retaining box was used to
      fix the FPD to the support teeth, and on whether a composite pontic was assembled
      on top of the fibers. Fracture testing was performed in a universal testing
      machine (1 mm/minute). Fracture strength values and failure types were
      statistically compared for each group. RESULTS: Using retaining boxes did not
      improve the mechanical behavior of the restorative system. The weakest element of
      the system was the composite tooth constructed on top of the FRC.

PMID- 26201229
TI  - In situ antimicrobial activity and inhibition of secondary caries of self-etching
      adhesives containing an antibacterial agent and/or fluoride.
AB  - PURPOSE: To evaluate the in situ effect of fluoride and MDPB-containing adhesives
      on antibacterial activity around restorations in conditions of high caries risk.
      METHODS: Bovine enamel and dentin blocks were restored with a fluoride-containing
      (One-up Bond F Plus - OP) or a MDPB and fluoride-containing adhesive (Clearfil
      Protect Bond - PB). Volunteers (n = 17) wore an intra-oral appliance containing
      three enamel and three dentin blocks, aligned side-by-side and restored with OP
      or PB and one enamel and dentin block (controls). The cariogenic challenge was
      carried out in two phases of 14 days each. The counts of total streptococci (TM),
      mutans streptococci (MS) and lactobacilli (LB) were analyzed in the biofilm
      formed. Cross-sectional microhardness (CSM) and polarized light microscopy (PLM)
      evaluated caries lesions around the restorations and the demineralization
      extension. Data obtained by CSM testing was analyzed by Split-Split Plot ANOVA (P
      < 0.05). PLM and microbiota results were analyzed by Wilcoxon test (P < 0.05).
      RESULTS: TM and MS counts were highest for the OP enamel restorations, and these
      presented higher lesion depths than PB in both the enamel and dentin. The CSM in
      dentin was the lowest at 60 MUm from the restoration wall. None of the adhesives
      prevented demineralization and bacteria growth, but PB reduced the amount of oral
      pathogens in enamel and demineralization around restorations in enamel and
      dentin.

PMID- 26201231
TI  - The Roots of Labor Day.

PMID- 26201230
TI  - Surface degradation of lithium disilicate ceramic after immersion in acid and
      fluoride solutions.
AB  - PURPOSE: To analyze whether immersion in sodium fluoride (NaF) solutions and/or
      common acidic beverages (test solutions) would affect the surface roughness or
      topography of lithium disilicate ceramic. METHODS: 220 ceramic discs were divided
      into four groups, each of which was subdivided into five subgroups (n = 11).
      Control group discs were immersed in one of four test beverages for 4 hours daily
      or in artificial saliva for 21 days. Discs in the experimental groups were
      continuously immersed in 0.05% NaF, 0.2% NaF, or 1.23% acidulated phosphate
      fluoride (APF) gel for 12, 73, and 48 hours, respectively, followed by immersion
      in one of the four test beverages or artificial saliva. Vickers microhardness,
      surface roughness, scanning electron microscopy (SEM) associated with energy
      dispersive spectroscopy, and atomic force microscopy (AFM) assessments were made.
      Data were analyzed by nested analysis of variance (ANOVA) and Tukey's test (alpha
      = 0.05). RESULTS: Immersion in the test solutions diminished the microhardness
      and increased the surface roughness of the discs. The test beverages promoted a
      significant reduction in the Vickers microhardness in the 0.05% and 0.2% NaF
      groups. The highest surface roughness results were observed in the 0.2% NaF and
      1.23% APF groups, with similar findings by SEM and AFM. Acidic beverages affected
      the surface topography of lithium disilicate ceramic. Fluoride treatments may
      render the ceramic surface more susceptible to the chelating effect of acidic
      solutions.

PMID- 26201232
TI  - Don't Sacrifice Safety for Productivity.

PMID- 26201233
TI  - Optical Clarity: Why It's Important and What It Means for You.

PMID- 26201234
TI  - Keeping Hand Injuries in Check.

PMID- 26201235
TI  - Modern Issues of First Aid Training.

PMID- 26201236
TI  - 'Anyone Can Help Save a Life'.

PMID- 26201237
TI  - Pros and Cons of Footwear Delivery Systems.

PMID- 26201238
TI  - The Asset Value of Employees.

PMID- 26201239
TI  - Selecting the Right Delivery Model and Service.

PMID- 26201240
TI  - Splashes & Sharps: Occupational Exposures in the Health Care Setting.

PMID- 26201241
TI  - LED-Driven Infrared Sensors.

PMID- 26201243
TI  - My Personal Leadership Mission.

PMID- 26201242
TI  - The Other Side of the Coin.

PMID- 26201244
TI  - Environmental water body characteristics in a major tributary backwater of the
      unique and strongly seasonal Three Gorges Reservoir, China.
AB  - Ecological consequences of large dams, particularly regarding the Three Gorges
      Dam (TGD) on the Yangtze River in China, have been controversially and
      internationally discussed. Water quality within the Three Gorges Reservoir (TGR)
      has been deteriorated by highly underestimated eutrophication and algal blooms.
      Globally, the TGR is delineated from other comparable reservoirs by its low mean
      water residence time and its 30 m annual water level fluctuation. We used an in
      situ and online multi-sensor system 'MINIBAT' to analyse eight indicative physico
      chemical parameters across depth and time within the Xiangxi River backwater, a
      representative major tributary of the TGR. The results revealed considerably
      changing environmental water body characteristics within the tributary backwater
      related to the TGR's typical seasonal hydrology. The Yangtze River main stream
      appeared to be the major contributor of dissolved and particulate water
      constituents within the Xiangxi River backwater. Eutrophication problems in
      spring and summer seasons are likely a consequence of extensive water mass
      exchange and pollutant transport processes in autumn and winter. In particular,
      the backwater's permanently stratified water column shows varying layered impacts
      of the Yangtze River main stream and Xiangxi River headwaters. This is a clear
      indication of a complex stratified flow pattern within this TGR tributary
      backwater. In our study, a major driver for the Yangtze River main stream impact
      was the rising TGR water level. The TGR's globally unique characteristics have
      thus become a central part of the recent eutrophication and pollution problem
      within the TGR. Thereof, we deduced a proposal for an adapted dam management
      strategy. 

PMID- 26201245
TI  - Neurexin-1 regulates sleep and synaptic plasticity in Drosophila melanogaster.
AB  - Neurexins are cell adhesion molecules that are important for synaptic plasticity
      and homeostasis, although links to sleep have not yet been investigated. We
      examined the effects of neurexin-1 perturbation on sleep in Drosophila, showing
      that neurexin-1 nulls displayed fragmented sleep and altered circadian rhythm.
      Conversely, the over-expression of neurexin-1 could increase and consolidate
      night-time sleep. This was not solely due to developmental effects as it could be
      induced acutely in adulthood, and was coupled with evidence of synaptic growth.
      The timing of over-expression could differentially impact sleep patterns, with
      specific night-time effects. These results show that neurexin-1 was dynamically
      involved in synaptic plasticity and sleep in Drosophila. Neurexin-1 and a number
      of its binding partners have been repeatedly associated with mental health
      disorders, including autism spectrum disorders, schizophrenia and Tourette
      syndrome, all of which are also linked to altered sleep patterns. How and when
      plasticity-related proteins such as neurexin-1 function during sleep can provide
      vital information on the interaction between synaptic homeostasis and sleep,
      paving the way for more informed treatments of human disorders. 

PMID- 26201246
TI  - Butanol production by a Clostridium beijerinckii mutant with high ferulic acid
      tolerance.
AB  - A mutant strain of Clostridium beijerinckii, with high tolerance to ferulic acid,
      was generated using atmospheric pressure glow discharge and high-throughput
      screening of C. beijerinckii NCIMB 8052. The mutant strain M11 produced 7.24 g/L
      of butanol when grown in P2 medium containing 30 g/L of glucose and 0.5 g/L of
      ferulic acid, which is comparable to the production from non-ferulic acid
      cultures (8.11 g/L of butanol). When 0.8 g/L of ferulic acid was introduced into
      the P2 medium, C. beijerinckii M11 grew well and produced 4.91 g/L of butanol.
      Both cell growth and butanol production of C. beijerinckii M11 were seriously
      inhibited when 0.9 g/L of ferulic acid was added into the P2 medium. Furthermore,
      C. beijerinckii M11 could produce 6.13 g/L of butanol using non-detoxified
      hemicellulosic hydrolysate from diluted sulfuric acid-treated corn fiber (SAHHC)
      as the carbon source. These results demonstrate that C. beijerinckii M11 has a
      high ferulic acid tolerance and is able to use non-detoxified SAHHC for butanol
      production.

PMID- 26201247
TI  - [Lateral column lengthening osteotomy of calcaneus].
AB  - OBJECTIVE: Lengthening of the lateral column for adduction of forefoot and
      restoration of the medial arch. Stabilization of the ankle joint complex.
      INDICATIONS: Supple flatfoot deformity (posterior tibial tendon dysfunction stage
      II). Instability of the medial ankle joint complex (superficial deltoid and
      spring ligament). Posttraumatic valgus and pronation deformity of the foot.
      CONTRAINDICATIONS: Rigid flatfoot deformity (posterior tibial tendon dysfunction
      stage III and IV). Talocalcaneal and naviculocalcaneal coalition. Osteoarthritis
      of calcaneocuboid joint. SURGICAL TECHNIQUE: Exposition of calcaneus at sinus
      tarsi. Osteotomy through sinus tarsi and widening until desired correction of the
      foot is achieved. Insertion of bone graft. Screw fixation. POSTOPERATIVE
      MANAGEMENT: Immobilization in a cast for 6 weeks. Weight-bearing as tolerated
      from the beginning. RESULTS: In the majority of cases, part of hindfoot
      reconstruction. Reliable and stable correction. Safe procedure with few
      complications.

PMID- 26201248
TI  - Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA
      PKcs phosphorylation and downregulation of XRCC4 and Ligase IV.
AB  - Although studies have shown that cadmium (Cd) interfered with DNA damage repair
      (DDR), whether Cd could affect non-homologous end joining (NHEJ) repair remains
      elusive. To further understand the effect of Cd on DDR, we used X-ray irradiation
      of Hela cells as an in vitro model system, along with gammaH2AX and 53BP1 as
      markers for DNA damage. Results showed that X-ray significantly increased
      gammaH2AX and 53BP1 foci in Hela cells (p < 0.01), all of which are
      characteristic of accrued DNA damage. The number of foci declined rapidly over
      time (1-8h postirradiation), indicating an initiation of NHEJ process. However,
      the disappearance of gammaH2AX and 53BP1 foci was remarkably slowed by Cd
      pretreatment (p < 0.01), suggesting that Cd reduced the efficiency of NHEJ. To
      further elucidate the mechanisms of Cd toxicity, several markers of NHEJ pathway
      including Ku70, DNA-PKcs, XRCC4 and Ligase IV were examined. Our data showed that
      Cd altered the phosphorylation of DNA-PKcs, and reduced the expression of both
      XRCC4 and Ligase IV in irradiated cells. These observations are indicative of the
      impairment of NHEJ-dependent DNA repair pathways. In addition, zinc (Zn)
      mitigated the effects of Cd on NHEJ, suggesting that the Cd-induced NHEJ
      alteration may partly result from the displacement of Zn or from an interference
      with the normal function of Zn-containing proteins by Cd. Our findings provide a
      new insight into the toxicity of Cd on NHEJ repair and its underlying mechanisms
      in human cells.

PMID- 26201249
TI  - Increased human AP endonuclease 1 level confers protection against the paternal
      age effect in mice.
AB  - Increased paternal age is associated with a greater risk of producing children
      with genetic disorders originating from de novo germline mutations. Mice mimic
      the human condition by displaying an age-associated increase in spontaneous
      mutant frequency in spermatogenic cells. The observed increase in mutant
      frequency appears to be associated with a decrease in the DNA repair protein, AP
      endonuclease 1 (APEX1) and Apex1 heterozygous mice display an accelerated
      paternal age effect as young adults. In this study, we directly tested if APEX1
      over-expression in cell lines and transgenic mice could prevent increases in
      mutagenesis. Cell lines with ectopic expression of APEX1 had increased APEX1
      activity and lower spontaneous and induced mutations in the lacI reporter gene
      relative to the control. Spermatogenic cells obtained from mice transgenic for
      human APEX1 displayed increased APEX1 activity, were protected from the age
      dependent increase in spontaneous germline mutagenesis, and exhibited increased
      apoptosis in the spermatogonial cell population. These results directly indicate
      that increases in APEX1 level confer protection against the murine paternal age
      effect, thus highlighting the role of APEX1 in preserving reproductive health
      with increasing age and in protection against genotoxin-induced mutagenesis in
      somatic cells. 

PMID- 26201250
TI  - Independent Emergence of the Cosmopolitan Asian Chikungunya Virus, Philippines
      2012.
AB  - Outbreaks involving the Asian genotype Chikungunya virus (CHIKV) caused over one
      million infections in the Americas recently. The outbreak was preceded by a major
      nationwide outbreak in the Philippines. We examined the phylogenetic and
      phylogeographic relationships of representative CHIKV isolates obtained from the
      2012 Philippines outbreak with other CHIKV isolates collected globally. Asian
      CHIKV isolated from the Philippines, China, Micronesia and Caribbean regions were
      found closely related, herein denoted as Cosmopolitan Asian CHIKV (CACV). Three
      adaptive amino acid substitutions in nsP3 (D483N), E1 (P397L) and E3 (Q19R) were
      identified among CACV. Acquisition of the nsP3-483N mutation in Compostela Valley
      followed by E1-397L/E3-19R in Laguna preceded the nationwide spread in the
      Philippines. The China isolates possessed two of the amino acid substitutions,
      nsP3-D483N and E1-P397L whereas the Micronesian and Caribbean CHIKV inherited all
      the three amino acid substitutions. The unique amino acid substitutions observed
      among the isolates suggest multiple independent virus dissemination events. The
      possible biological importance of the specific genetic signatures associated with
      the rapid global of the virus is not known and warrant future in-depth study and
      epidemiological follow-up. Molecular evidence, however, supports the Philippines
      outbreak as the possible origin of the CACV. 

PMID- 26201251
TI  - Daily costs of hospitalization in non-valvular atrial fibrillation patients
      treated with anticoagulant therapy.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac rhythm
      disturbance in the US, with an estimated prevalence of 2.7-6.1 million persons in
      2010. OBJECTIVE: This study evaluates the progression of daily hospitalization
      costs among non-valvular atrial fibrillation (NVAF) patients treated with
      anticoagulant therapy. METHODS: A claims analysis was conducted with Premier
      Perspective Comparative Hospital Database records from January 2009-March 2013.
      Patients of 18 years or older who were diagnosed with NVAF and used anticoagulant
      therapy were studied. Treatment patterns and mean daily costs of hospitalization
      per patient as well as total costs of hospitalization were reported. Comparisons
      of mean daily costs with those of the previous day were presented to identify
      statistical cost differences between hospitalization days. RESULTS: A total of
      375,560 patients were identified; 67,017 with AF as admitting/primary diagnosis,
      and 308,543 with AF as a secondary diagnosis. The mean age of the overall
      population, primary AF diagnosis cohort, and secondary AF diagnosis cohort was
      73.8, 67.9, and 75.0 years, while their proportion of females was 46.3%, 45.6%,
      and 46.5%, respectively. The mean length of stay was 6.8 days, 3.7 days, and 7.5
      days for the overall population, the primary AF diagnosis cohort, and the
      secondary AF diagnosis cohort, respectively. For all cohorts, mean daily costs
      stabilized on the third day (overall population: $2103; primary AF diagnosis
      cohort: $1505; secondary AF diagnosis cohort: $2208). LIMITATIONS: Claims data
      may have contained inaccuracies or omissions in coded procedures, diagnoses, or
      pharmacy claims. CONCLUSION: The study showed that daily hospitalization costs
      for NVAF patients stabilized on the third day of hospitalization and that any
      reduction or prolongation in hospital length of stay could have a significant
      impact on the cost burden associated with AF.

PMID- 26201252
TI  - Evaluating the economic implications of non-adherence and antibody-mediated
      rejection in renal transplant recipients: the role of once-daily tacrolimus in
      the UK.
AB  - BACKGROUND AND AIMS: While short-term kidney graft survival has gradually
      improved over time, improvements in long-term graft survival have been more
      modest. One key clinical factor limiting improved longer-term outcomes is
      antibody-mediated rejection (AbMR), the incidence of which appears to be higher
      in patients who are non-adherent to immunosuppressants. Recent data show that
      adherence can be improved by reducing pill burden. The aim of the present study
      was to model the incidence and economic consequences of graft loss and AbMR in
      patients taking once- vs twice-daily tacrolimus in the UK. METHODS: A combined
      decision tree and Markov model was developed to estimate the incidence of graft
      failure, AbMR and mortality in renal transplant recipients taking once- vs twice
      daily tacrolimus. Underlying rates of graft failure and mortality were derived
      from UK-specific sources. Proportions of patients adherent to once- vs twice
      daily tacrolimus were taken from a recent randomized clinical trial and relative
      risks of graft failure and AbMR were taken from a prospective, multi-center
      analysis of 315 patients. Cost data were taken from the British National
      Formulary and National Health Service reference costs and reported in 2014 pounds
      sterling. RESULTS: Modeling results showed that improved adherence would be
      associated with reduced incidence of AbMR and graft failure in renal transplant
      recipients. Based on improvements in adherence resulting from switching from
      twice-daily to once-daily tacrolimus, the modeling analysis projected cost
      savings of GBP 4862 per patient over 5 years with Advagraf relative to Prograf,
      on absolute costs of GBP 40,974 and GBP 45,836, respectively. CONCLUSIONS: Using
      Advagraf in place of Prograf in renal transplant recipients was predicted to be
      associated with lower pharmacy, dialysis and AbMR treatment costs, with the
      reduction in AbMR and dialysis costs being driven by improved adherence to the
      Advagraf regimen and consequent reductions in graft failure and onset of AbMR.

PMID- 26201253
TI  - Vocal fold mobility as the main prognostic factor of treatment outcomes and
      survival in stage II squamous cell carcinomas of the glottic larynx.
AB  - OBJECTIVE: This study aimed to assess the influence of supra- and subglottic
      extensions and vocal fold mobility on outcome in a large monocentric cohort of
      148 patients treated for tumour-node-metastasis stage T2N0 glottic carcinomas.
      METHODS: In all, 107 glottic carcinoma patients had normal vocal fold mobility
      (T2aN0), and 41 had impaired vocal fold mobility (T2bN0). Treatment decisions
      were made by a multidisciplinary team. RESULTS: Vocal fold mobility was
      associated with overall survival, disease-free survival, local control, larynx
      preservation and laryngectomy-free survival. For patients with T2a lesions, local
      control, laryngectomy-free survival and disease-free survival improved after
      surgery but overall survival did not. For patients with T2b lesions, local
      control, laryngectomy-free survival, disease-free survival and overall survival
      were all higher after surgery than after radiotherapy. CONCLUSION: This study
      highlights for the first time the importance of vocal fold mobility in treatment
      outcomes and is the first to assess its influence on survival. Updated tumour
      node-metastasis classifications should consider the distinction between T2a and
      T2b lesions.

PMID- 26201254
TI  - Estimated Glomerular Filtration Rate Variability Independently Predicts Renal
      Prognosis in Advanced Chronic Kidney Disease Patients.
AB  - BACKGROUND: We often experience visit-to-visit estimated glomerular filtration
      rate (eGFR) variability among patients with advanced chronic kidney disease
      (CKD). However, the impact of eGFR variability on renal prognosis is not well
      understood. METHODS: The Kanagawa Valsartan Trial was a multicenter, randomized,
      open-label trial that compared the effect of add-on treatment with angiotensin II
      receptor blocker, valsartan, with that of conventional treatment on the rate of
      CKD progression in 293 advanced CKD patients. In this post hoc analysis, we
      compared the effect of high eGFR variability on end-stage renal disease (ESRD).
      To evaluate eGFR variability, we chose participants with >= 5 serial measurements
      of eGFR during the study period and assessed the residual coefficient of
      variation (CV) of eGFR (residual eGFR-CV) derived from a regression line of eGFR
      (eGFR slope). The primary end point was the first event of ESRD. RESULTS: Among
      237 patients with >= 5 serial measurements of eGFR in a median follow-up of 1.47
      years, there were 54 ESRD events in the higher than median residual eGFR-CV group
      and 36 ESRD events in the lower than median eGFR-CV group (log-rank test, p =
      0.008). In multivariate Cox regression analysis, high eGFR variability was
      significantly associated with the primary end point as well as hypertension, high
      proteinuria, low baseline eGFR and steep eGFR slope (hazards ratio 2.11, 95% CI
      1.33-3.33, p = 0.001). CONCLUSION: High eGFR variability predicts poor renal
      prognosis; therefore, further attention is warranted for ambulatory patients with
      large eGFR fluctuations, especially those with advanced CKD.

PMID- 26201255
TI  - Towards photodetection with high efficiency and tunable spectral selectivity:
      graphene plasmonics for light trapping and absorption engineering.
AB  - Plasmonics can be used to improve absorption in optoelectronic devices and has
      been intensively studied for solar cells and photodetectors. Graphene has
      recently emerged as a powerful plasmonic material. It shows significantly less
      loss compared to traditional plasmonic materials such as gold and silver and its
      plasmons can be tuned by changing the Fermi energy with chemical or electrical
      doping. Here we propose the use of graphene plasmonics for light trapping in
      optoelectronic devices and show that the excitation of localized plasmons in
      doped, nanostructured graphene can enhance optical absorption in its surrounding
      medium including both bulky and two-dimensional materials by tens of times, which
      may lead to a new generation of photodetectors with high efficiency and tunable
      spectral selectivity in the mid-infrared and THz ranges. 

PMID- 26201256
TI  - Gel-free mass spectrometry analysis of Drosophila melanogaster heads.
AB  - Membrane proteins play key roles in several fundamental biological processes such
      as cell signalling, energy metabolism and transport. Despite the significance,
      these still remain an under-represented group in proteomics datasets. Herein, a
      bottom-up approach to analyse an enriched membrane fraction from Drosophila
      melanogaster heads using multidimensional liquid chromatography (LC) coupled with
      tandem-mass spectrometry (MS/MS) that relies on complete solubilisation and
      digestion of proteins, is reported. An enriched membrane fraction was prepared
      using equilibrium density centrifugation on a discontinuous sucrose gradient,
      followed by solubilisation using the filter-aided sample preparation (FASP),
      tryptic and sequential chymotryptic digestion of proteins. Peptides were
      separated by reversed-phase (RP) LC at high pH in the first dimension and acidic
      RP-LC in the second dimension coupled directly to an Orbitrap Velos Pro mass
      spectrometer. A total number of 4812 proteins from 114 865 redundant and 38 179
      distinct peptides corresponding to 4559 genes were identified in the enriched
      membrane fraction from fly heads. These included brain receptors, transporters
      and channels that are most important elements as drug targets or are linked to
      disease. Data are available via ProteomeXchange with identifier PXD001712
      (http://proteomecentral.proteomexchange.org/dataset/PXD001712).

PMID- 26201257
TI  - Nurses as therapeutic agents in the extreme environment of the desert war, 1940
      44.
AB  - AIMS: The purpose of this article is to explore therapeutic nursing with
      combatants in the extreme environment of the desert in World War II. BACKGROUND:
      The notion of nursing as therapy gained credence in the 1990s and is currently
      experiencing resurgence, as nurses seek to find meaning in their work and improve
      patient care in the post-Francis environment. DESIGN: This discussion paper will
      use the hostile space of the desert war zone in World War II to explore nurses'
      therapeutic engagement with their combatant patients. It will examine how nurses
      provided care and comfort through the use of self, fundamental nursing skills,
      improvisation and innovation and the manipulation of the environment. DATA
      SOURCES: The data used are a combination of letters, diaries, memoirs and
      published archival material. Much of the personal testimony is part of an
      uncatalogued archive of correspondence between nurses and the Matron-in-Chief of
      the Queen Alexandra's Imperial Military Nursing Service. IMPLICATIONS FOR
      NURSING: Nurses sometimes struggle to identify the importance of their work,
      compared with other members of the multidisciplinary team. By understanding
      nursing as therapy, the profession can articulate how their work is fundamental
      to the healing, or support to a dignified death of their patients. This article
      illustrates how the therapeutic engagement with patients, even in the most
      difficult of environments, is possible and brings comfort. CONCLUSION: Deserts
      are among the most hostile of any space inhabited by people. Yet, even in a place
      where survival is difficult, therapeutic nursing can support healing and
      recovery.

PMID- 26201258
TI  - TFF2, a MUC6-binding lectin stabilizing the gastric mucus barrier and more
      (Review).
AB  - The peptide TFF2 (formerly 'spasmolytic polypeptide'), a member of the trefoil
      factor family (TFF) containing two TFF domains, is mainly expressed together with
      the mucin MUC6 in the gastric epithelium and duodenal Brunner's glands.
      Pathologically, TFF2 expression is observed ectopically during stone diseases,
      chronic inflammatory conditions and in several metaplastic and neoplastic
      epithelia; most prominent being the 'spasmolytic polypeptide-expressing
      metaplasia' (SPEM), which is an established gastric precancerous lesion. TFF2
      plays a critical role in maintaining gastric mucosal integrity and appears to
      restrain tumorigenesis in the stomach. Recently, porcine TFF2 has been shown to
      interact with the gastric mucin MUC6 and thus stabilize the gastric mucus
      barrier. On the one hand, TFF2 binds to MUC6 via non-covalent lectin interactions
      with the glycotope GlcNAcalpha1->4Galbeta1->R. On the other hand, TFF2 is
      probably also covalently bound to MUC6 via disulfide bridges. Thus, implications
      for the complex multimeric assembly, cross-linking, and packaging of MUC6 as well
      as the rheology of gastric mucus are discussed in detail in this review.
      Furthermore, TFF2 is also expressed in minor amounts in the immune and nervous
      systems. Thus, similar to galectins, its lectin activity would perfectly enable
      TFF2 to form multivalent complexes and cross-linked lattices with a plethora of
      transmembrane glycoproteins and thus modulate different signal transduction
      processes. This could explain the multiple and diverse biological effects of TFF2
      [e.g., motogenic, (anti)apoptotic, and angiogenic effects]. Finally, a function
      during fertilization is also possible for TFF domains because they occur as
      shuffled modules in certain zona pellucida proteins. 

PMID- 26201259
TI  - Social Media Use in Research: Engaging Communities in Cohort Studies to Support
      Recruitment and Retention.
AB  - BACKGROUND: This paper presents the first formal evaluation of social media (SM)
      use in the National Children's Study (NCS). The NCS is a prospective,
      longitudinal study of the effects of environment and genetics on children's
      health, growth and development. The Study employed a multifaceted community
      outreach campaign in combination with a SM campaign to educate participants and
      their communities about the Study. SM essentially erases geographic differences
      between people due to its omnipresence, which was an important consideration in
      this multi-site national study. Using SM in the research setting requires an
      understanding of potential threats to confidentiality and privacy and the role
      that posted content plays as an extension of the informed consent process.
      OBJECTIVE: This pilot demonstrates the feasibility of creating linkages and
      databases to measure and compare SM with new content and engagement metrics.
      METHODS: Metrics presented include basic use metrics for Facebook as well as
      newly created metrics to assist with Facebook content and engagement analyses.
      RESULTS: Increasing Likes per month demonstrates that online communities can be
      quickly generated. Content and Engagement analyses describe what content of posts
      NCS Study Centers were using, what content they were posting about, and what the
      online NCS communities found most engaging. CONCLUSIONS: These metrics highlight
      opportunities to optimize time and effort while determining the content of future
      posts. Further research about content analysis, optimal metrics to describe
      engagement in research, the role of localized content and stakeholders, and
      social media use in participant recruitment is warranted.

PMID- 26201260
TI  - Do birds see the forest for the trees? Scale-dependent effects of tree diversity
      on avian predation of artificial larvae.
AB  - The enemies hypothesis states that reduced insect herbivory in mixed-species
      stands can be attributed to more effective top-down control by predators with
      increasing plant diversity. Although evidence for this mechanism exists for
      invertebrate predators, studies on avian predation are comparatively rare and
      have not explicitly tested the effects of diversity at different spatial scales,
      even though heterogeneity at macro- and micro-scales can influence bird foraging
      selection. We studied bird predation in an established forest diversity
      experiment in SW Finland, using artificial larvae installed on birch, alder and
      pine trees. Effects of tree species diversity and densities on bird predation
      were tested at two different scales: between plots and within the neighbourhood
      around focal trees. At the neighbourhood scale, birds preferentially foraged on
      focal trees surrounded by a higher diversity of neighbours. However, predation
      rates did not increase with tree species richness at the plot level and were
      instead negatively affected by tree height variation within the plot. The highest
      probability of predation was observed on pine, and rates of predation increased
      with the density of pine regardless of scale. Strong tree species preferences
      observed may be due to a combination of innate bird species preferences and
      opportunistic foraging on profitable-looking artificial prey. This study
      therefore finds partial support for the enemies hypothesis and highlights the
      importance of spatial scale and focal tree species in modifying trophic
      interactions between avian predators and insect herbivores in forest ecosystems. 

PMID- 26201261
TI  - Temporal trends and sources of variation in carbon flux from coarse woody debris
      in experimental forest canopy openings.
AB  - Pulses of respiration from coarse woody debris (CWD) have been observed
      immediately following canopy disturbances, but it is unclear how long these
      pulses are sustained. Several factors are known to influence carbon flux rates
      from CWD, but few studies have evaluated more than temperature and moisture. We
      experimentally manipulated forest structure in a second-growth northern hardwood
      forest and measured CO2 flux periodically for seven growing seasons following gap
      creation. We present an analysis of which factors, including the composition of
      the wood-decay fungal community influence CO2 flux. CO2 flux from CWD was
      strongly and positively related to wood temperature and varied significantly
      between substrate types (logs vs. stumps). For five growing seasons after
      treatment, the CO2 flux of stumps reached rates up to seven times higher than
      that of logs. CO2 flux of logs did not differ significantly between canopy-gap
      and closed-canopy conditions in the fourth through seventh post-treatment growing
      seasons. By the seventh season, the seasonal carbon flux of both logs and stumps
      had decreased significantly from prior years. Linear mixed models indicated the
      variation in the wood inhabiting fungal community composition explained a
      significant portion of variability in the CO2 flux along with measures of
      substrate conditions. CO2 flux rates were inversely related to fungal diversity,
      with logs hosting more species but emitting less CO2 than stumps. Overall, our
      results suggest that the current treatment of CWD in dynamic forest carbon models
      may be oversimplified, thereby hampering our ability to predict realistic carbon
      fluxes associated with wood decomposition. 

PMID- 26201262
TI  - Detection and categorization of bacteria habitats using shallow linguistic
      analysis.
AB  - BACKGROUND: Information regarding bacteria biotopes is important for several
      research areas including health sciences, microbiology, and food processing and
      preservation. One of the challenges for scientists in these domains is the huge
      amount of information buried in the text of electronic resources. Developing
      methods to automatically extract bacteria habitat relations from the text of
      these electronic resources is crucial for facilitating research in these areas.
      METHODS: We introduce a linguistically motivated rule-based approach for
      recognizing and normalizing names of bacteria habitats in biomedical text by
      using an ontology. Our approach is based on the shallow syntactic analysis of the
      text that include sentence segmentation, part-of-speech (POS) tagging, partial
      parsing, and lemmatization. In addition, we propose two methods for identifying
      bacteria habitat localization relations. The underlying assumption for the first
      method is that discourse changes with a new paragraph. Therefore, it operates on
      a paragraph-basis. The second method performs a more fine-grained analysis of the
      text and operates on a sentence-basis. We also develop a novel anaphora
      resolution method for bacteria coreferences and incorporate it with the sentence
      based relation extraction approach. RESULTS: We participated in the Bacteria
      Biotope (BB) Task of the BioNLP Shared Task 2013. Our system (Boun) achieved the
      second best performance with 68% Slot Error Rate (SER) in Sub-task 1 (Entity
      Detection and Categorization), and ranked third with an F-score of 27% in Sub
      task 2 (Localization Event Extraction). This paper reports the system that is
      implemented for the shared task, including the novel methods developed and the
      improvements obtained after the official evaluation. The extensions include the
      expansion of the OntoBiotope ontology using the training set for Sub-task 1, and
      the novel sentence-based relation extraction method incorporated with anaphora
      resolution for Sub-task 2. These extensions resulted in promising results for Sub
      task 1 with a SER of 68%, and state-of-the-art performance for Sub-task 2 with an
      F-score of 53%. CONCLUSIONS: Our results show that a linguistically-oriented
      approach based on the shallow syntactic analysis of the text is as effective as
      machine learning approaches for the detection and ontology-based normalization of
      habitat entities. Furthermore, the newly developed sentence-based relation
      extraction system with the anaphora resolution module significantly outperforms
      the paragraph-based one, as well as the other systems that participated in the BB
      Shared Task 2013.

PMID- 26201263
TI  - The face of conservation responding to a dynamically changing world.
AB  - In its 40-year history, the science of conservation has faced unprecedented
      challenges in terms of environmental damage and rapid global change, and
      environmental problems are only increasing as greater demands are placed on
      limited natural resources. Conservation science has been adapting to keep pace
      with these changes. Here, we highlight contemporary and emerging trends and
      innovations in conservation science that we believe represent the most effective
      responses to biodiversity threats. We focus on specific areas where conservation
      science has had to adjust its approach to address emerging threats to
      biodiversity, including habitat destruction and degradation, climate change,
      declining populations and invasive species. We also document changes in
      attitudes, norms and practices among conservation scientists. A key component to
      success is engaging and maintaining public support for conservation, which can be
      facilitated through the use of technology. These recent trends in conservation
      and management are innovative and will assist in optimizing conservation
      strategies, increasing our leverage with the general public and tackling our
      current environmental challenges. 

PMID- 26201264
TI  - High-Dose Chemotherapy and Autologous Stem Cell Transplant in Older Patients with
      Lymphoma.
AB  - High-dose chemotherapy followed by autologous hematopoietic stem cell transplant
      (HDT/ASCT) can improve survival in patients with lymphoma. Limited experience is
      available on the safety and efficacy of HDT/ASCT in elderly patients. In this
      article, we review the published data on the role of HDT/ASCT in management of
      lymphoma in older patients. Based on available data, evaluation of comorbidities,
      functional status, and comprehensive geriatric assessment (CGA) will help
      identify those who can benefit most from this intervention. Prospective clinical
      trials focusing on HDT/ASCT in older patients with lymphoma are needed to
      establish optimal management protocols in this select population. 

PMID- 26201265
TI  - Assessment of Protective Role of Multifunctional Dopamine Agonist D-512 Against
      Oxidative Stress Produced by Depletion of Glutathione in PC12 Cells: Implication
      in Neuroprotective Therapy for Parkinson's Disease.
AB  - Oxidative stress has been strongly implicated in the progression of Parkinson's
      disease (PD). Depletion of cytoplasmic glutathione levels is one of the
      indications of oxidative stress, which occur in the substantia nigra of PD
      patients at an early stage of the disease process. It has been shown that
      glutathione depletion causes the inhibition of mitochondrial complex I, thus
      affecting mitochondrial function leading to oxidative stress via production of
      reactive oxygen species. Studies were carried out to investigate the role of D
      512, a potent multifunctional neuroprotective D2/D3 receptor agonist, in
      protecting dopaminergic PC12 cells treated with buthionine sulfoximine (BSO), an
      inhibitor of key enzyme in glutathione synthesis and 6-hydroxydopamine (6-OHDA),
      a widely used neurotoxin. D-512 was able to restore level of glutathione against
      BSO/6-OHDA-mediated glutathione depletion. D-512 also showed significant
      neuroprotection in PC12 cells against toxicity induced by combined treatment of
      BSO and 6-OHDA. Furthermore, D-512 was able to restore both phospho-extracellular
      signal-regulated kinase and phospho-Jun N-terminal kinase levels upon treatment
      with 6-OHDA providing an evidence on the possible mechanism of action for
      neuroprotection by modulating mitogen-activated protein kinases. We have further
      demonstrated the neuroprotective effects of D-512 against oxidative insult
      produced by BSO and 6-OHDA in PC12 cells. 

PMID- 26201267
TI  - A National Survey of Traumatic Brain Injuries Admitted to Hospitals in Sweden
      from 1987 to 2010.
AB  - BACKGROUND: With an increasing and aging population, there is a global demand for
      improving the primary prevention strategies aimed at reducing traumatic brain
      injuries (TBIs). The objective of the present epidemiological study was to
      evaluate the pattern of TBI in Sweden over a 24 years period (1987-2010).
      METHODS: The Swedish Hospital Discharge Register was used, where in-patient care
      with a main diagnosis of TBI according to ICD9/10 was included. External factors,
      age and gender distribution was evaluated. RESULTS: A decreasing number of annual
      incidence was observed, that is, from 230 to 156 per 100,000 inhabitants. A
      steady decrease of concussion was observed while other intracranial injuries
      increased especially traumatic subdural hemorrhage and subarachnoid hemorrhage.
      The study identified 3 groups of patients - young, adults and elderly. The
      highest incidence and the largest increase of incidence were seen in the oldest
      age group (85+ years) while the population under 65 years had a decreasing
      incidence of TBI. The most frequent etiology was fall accidents (57%) with a
      relative constant trend over the study period. CONCLUSIONS: More effort should be
      focused on different strategies for different age groups, especially the elderly
      group. A well-planned strategy for primary prevention guidelines for different
      age groups will have the chance to further reduce not only the health-care costs
      but also complications among elderly care.

PMID- 26201266
TI  - CHD1L Regulated PARP1-Driven Pluripotency and Chromatin Remodeling During the
      Early-Stage Cell Reprogramming.
AB  - PARP1 and poly(ADP-ribosyl)ation (PARylation) have been shown to be essential for
      the initial steps of cellular reprogramming. However, the mechanism underlying
      PARP1/PARylation-regulated activation of pluripotency loci remains undetermined.
      Here, we demonstrate that CHD1L, a DNA helicase, possesses chromatin remodeling
      activity and interacts with PARP1/PARylation in regulating pluripotency during
      reprogramming. We found that this interaction is mediated through the interplay
      of the CHD1L macro-domain and the PAR moiety of PARylated-PARP1. Chromatin
      immunoprecipitation assays demonstrated the co-occupancy of CHD1L and PARP1 at
      Pou5f1, Nanog, and Esrrb pluripotency loci. Knockdown of CHD1L significantly
      blocked the binding activity of PARP1 at pluripotency loci and inhibited the
      efficiency of PARP1-driven reprogramming. Notably, we found that CHD1L-promoted
      reprogramming requires both a PARP1-interacting domain and DNA helicase activity,
      partly contributing to the chromatin-remodeling states of pluripotency loci.
      Taken together, these results identify CHD1L as a key chromatin remodeler
      involved in PARP1/PARylation-regulated early-stage reprogramming and pluripotency
      in stem cells.

PMID- 26201268
TI  - Third type of domain wall in soft magnetic nanostrips.
AB  - Magnetic domain walls (DWs) in nanostructures are low-dimensional objects that
      separate regions with uniform magnetisation. Since they can have different shapes
      and widths, DWs are an exciting playground for fundamental research, and became
      in the past years the subject of intense works, mainly focused on controlling,
      manipulating, and moving their internal magnetic configuration. In nanostrips
      with in-plane magnetisation, two DWs have been identified: in thin and narrow
      strips, transverse walls are energetically favored, while in thicker and wider
      strips vortex walls have lower energy. The associated phase diagram is now well
      established and often used to predict the low-energy magnetic configuration in a
      given magnetic nanostructure. However, besides the transverse and vortex walls,
      we find numerically that another type of wall exists in permalloy nanostrips.
      This third type of DW is characterised by a three-dimensional, flux closure
      micromagnetic structure with an unusual length and three internal degrees of
      freedom. Magnetic imaging on lithographically-patterned permalloy nanostrips
      confirms these predictions and shows that these DWs can be moved with an external
      magnetic field of about 1 mT. An extended phase diagram describing the regions of
      stability of all known types of DWs in permalloy nanostrips is provided. 

PMID- 26201269
TI  - Carriers of Autosomal Recessive Alport Syndrome with Thin Basement Membrane
      Nephropathy Presenting as Focal Segmental Glomerulosclerosis in Later Life.
AB  - Collagen IV nephropathies (COL4Ns) comprise benign familial microscopic
      hematuria, thin basement membrane nephropathy (TBMN), X-linked Alport syndrome
      (AS) and also autosomal recessive and dominant AS. Apart from the X-linked form
      of AS, which is caused by hemizygous mutations in the COL4A5 gene, the other
      entities are caused by mutations in the COL4A3 or COL4A4 genes. The diagnosis of
      these conditions used to be based on clinical and/or histological findings of
      renal biopsies, but it is the new molecular genetics approach that revolutionised
      their investigation and proved particularly instrumental, especially, in many not
      so clear-cut cases. More recently, the spectrum of COL4N has expanded to include
      late onset focal segmental glomerulosclerosis (FSGS) that develops on top of TBMN
      in later life. Also, other reports showed that some patients with a primary
      diagnosis of familial FSGS proved to have variants in COL4 genes. In the presence
      of a renal biopsy picture of FSGS and in the absence of either electron
      microscopy studies or molecular genetic studies that point to TBMN and COL4N, the
      patient and his family may be mistakenly diagnosed with hereditary FSGS leading
      to unnecessary further investigations, erroneous family counselling and improper
      corticosteroid treatment. TBMN is a frequent finding in the general population,
      and according to several recent reports, it may be the underlying cause and the
      explanation for many familial and sporadic cases of late-onset FSGS with non
      nephrotic proteinuria. This is an important new finding that needs widespread
      recognition. It is anticipated that the molecular genetic analysis with next
      generation sequencing will certainly offer timely correct diagnosis.

PMID- 26201270
TI  - Functions of neurofilaments in synapses.

PMID- 26201271
TI  - Biomaterials in Relation to Dentistry.
AB  - Dental caries remains a challenge in the improvement of oral health. It is the
      most common and widespread biofilm-dependent oral disease, resulting in the
      destruction of tooth structure by the acidic attack from cariogenic bacteria. The
      tooth is a heavily mineralised tissue, and both enamel and dentine can undergo
      demineralisation due to trauma or dietary conditions. The adult population
      worldwide affected by dental caries is enormous and despite significant advances
      in caries prevention and tooth restoration, treatments continue to pose a
      substantial burden to healthcare. Biomaterials play a vital role in the
      restoration of the diseased or damaged tooth structure and, despite providing
      reasonable outcomes, there are some concerns with clinical performance. Amalgam,
      the silver grey biomaterial that has been widely used as a restorative material
      in dentistry, is currently in throes of being phased out, especially with the
      Minimata convention and treaty being signed by a number of countries (January
      2013; http://mercuryconvention.org/Convention/) that aims to control the
      anthropogenic release of mercury in the environment, which naturally impacts the
      use of amalgam, where mercury is a component. Thus, the development of
      alternative restoratives and restoration methods that are inexpensive, can be
      used under different climatic conditions, withstand storage and allow easy
      handling, the main prerequisites of dental biomaterials, is important. The
      potential for using biologically engineered tissue and consequent research to
      replace damaged tissues has also seen a quantum leap in the last decade. Ongoing
      research in regenerative treatments in dentistry includes alveolar ridge
      augmentation, bone tissue engineering and periodontal ligament replacement, and a
      future aim is bioengineering of the whole tooth. Research towards developing
      bioengineered teeth is well underway and identification of adult stem cell
      sources to make this a viable treatment is advancing; however, this topic is not
      in the scope of this chapter. Whilst research focuses on many different aspects,
      operative dentistry involves the wide use of restorative biomaterials; thus, the
      development of smart biomaterials to suit the current climes of minimally
      invasive dentistry is important. The concept of minimally invasive dentistry
      primarily promotes preservation of the natural tissue, and, thus, the prevention
      of disease or the advancement of procedures that allow early detection and
      interception of its progress with minimal tissue loss are of significance. This
      chapter presents, in brief, the current state of the art of direct restorative
      biomaterials and their role and future in the field of dentistry. Modern dental
      practice is highly reliant on the selection of appropriate materials for optimum
      function and benefit to the patient. Dentistry, perhaps, has the unique
      distinction of using the widest variety of materials, ranging from polymers,
      metals, ceramics, inorganic salts to composite materials. So far, aesthetics of
      restorative materials and their ability to perform in the harsh oral environment
      without undergoing changes in dimension and stability has been the major focus of
      materials used in dentistry. Despite advances in tissue engineering and
      regeneration in the field of regenerative medicine, this concept has found
      relatively limited application for enamel and dentine due to their limited
      ability to remodel, but research related to biomimetic approaches for the
      modification of dentine is a significant step.

PMID- 26201272
TI  - Polymer Therapeutics in Relation to Dentistry.
AB  - The successful clinical application arising from advances in polymer and
      macromolecular sciences in different fields of medicine has opened new
      explorative approaches for the future design and development of the ever more
      sophisticated bio-/nanotechnologies that are needed to realise the full potential
      of modern dentistry. In this chapter, the most recent polymer therapeutic
      approaches for alveolar ridge augmentation, bone grafts, periodontal disease,
      restorative materials and scaffolds or carriers for cell-based therapies are
      presented highlighting the potential of either synthetic or natural polymers,
      such as polyesters, polyolefins, polyacrylates or chitosan for example, being
      tailored and engineered to yield a range of properties valuable in the design and
      development of dental polymer therapeutics.

PMID- 26201273
TI  - Biological Impact of Bioactive Glasses and Their Dissolution Products.
AB  - For many years, bioactive glasses (BGs) have been widely considered for bone
      tissue engineering applications due to their ability to bond to hard as well as
      soft tissue (a property termed bioactivity) and for their stimulating effects on
      bone formation. Ionic dissolution products released during the degradation of the
      BG matrix induce osteogenic gene expression leading to enhanced bone
      regeneration. Recently, adding bioactive metallic ions (e.g. boron, copper,
      cobalt, silver, zinc and strontium) to silicate (or phosphate and borate) glasses
      has emerged as a promising route for developing novel BG formulations with
      specific therapeutic functionalities, including antibacterial, angiogenic and
      osteogenic properties. The degradation behaviour of BGs can be tailored by
      adjusting the glass chemistry making these glass matrices potential carrier
      systems for controlled therapeutic ion release. This book chapter summarises the
      fundamental aspects of the effect of ionic dissolution products from BGs on
      osteogenesis and angiogenesis, whilst discussing novel BG compositions with
      controlled therapeutic ion release.

PMID- 26201274
TI  - Organic-Inorganic Composites Toward Biomaterial Application.
AB  - Bioactive ceramics are known to exhibit specific biological affinities and are
      able to show direct integration with surrounding bone when implanted in bony
      defects. However, their inadequate mechanical properties, such as low fracture
      toughness and high Young's modulus in comparison to natural bone, limit their
      clinical application. Bone is a kind of organic-inorganic composite where apatite
      nanocrystals are precipitated onto collagen fibre networks. Thus, one way to
      address these problems is to mimic the natural composition of bone by using
      bioactive ceramics via material designs based on organic-inorganic composites. In
      this chapter, the current research on the development of the various organic
      inorganic composites designed for biomaterial applications has been reviewed.
      Various compounds such as calcium phosphate, calcium sulphate and calcium
      carbonate can be used for the inorganic phases to design composites with the
      desired mechanical and biological properties of bone. Not only classical
      mechanical mixing but also coating of the inorganic phase in aqueous conditions
      is available for the fabrication of such composites. Organic modifications using
      various polymers enable the control of the crystalline structure of the calcium
      carbonate in the composites. These approaches on the fabrication of organic
      inorganic composites provide important options for biomedical materials with
      novel functions.

PMID- 26201275
TI  - New Advanced Materials for High Performance at the Resin-Dentine Interface.
AB  - This chapter provides a tool for the integration of new concepts and biomaterials
      related with the resin-dentine interface. The principles of dentine
      demineralisation and remineralisation that shape modern restorative dentistry
      practices, as well as considerations for the selection of new materials for
      different restorative approaches, are emphasised. Re-incorporation of mineral
      into the demineralised dentine matrix is important since the mineral precipitated
      may work as a constant site for further nucleation, and the remineralised
      subsurface of the tissue may be more resistant to subsequent acid attack. This
      deposition of minerals may be due to both spontaneous precipitation induced by
      local supersaturation of Ca and P in the presence of non-specific tissue alkaline
      phosphatase or through heterogeneous nucleation sites provided by phosphoproteins
      within the dentine collagen matrix. Nucleation is a multistep process involving
      both protein and mineral transition and suggests a temporally synchronised
      process. Dentine provides both structural and chemical frameworks, acting as a
      scaffold for mineral deposition at specific sites. The ultimate goal in the
      design and improvement of new materials for high performance at the resin-dentine
      interface is to render a stronger and durable adhesion to dental tissues despite
      the severe conditions in the oral environment. In the present chapter, glass
      ionomers, calcium-phosphate cements and doped dental adhesives have been selected
      to represent the cutting edge biomaterials at the interface.

PMID- 26201276
TI  - Nanobiomaterial Coatings in Dentistry.
AB  - During the last decade, there has been a major increase in the interest of
      nanostructured materials in advanced technologies for biomedical and dental
      clinical applications. Nanostructured materials are associated with a variety of
      applications within the dental and biomedical field, for example nanoparticles in
      drug delivery systems and nanostructured scaffolds in tissue engineering. More
      importantly, nanotechnology has also been linked with the modification of surface
      properties of synthetic implants in an attempt to improve their bioactivity,
      reliability and protection from the release of harmful or unnecessary metal ions.
      This is achieved through the use of nanocoatings and nanocomposite coatings.
      These new-generation coatings based on inorganic materials and biological
      materials such as proteins and peptides are currently investigated and applied.
      This chapter aims to give an overview of the recent advances in nanocoatings and
      their composites being investigated or used in dentistry.

PMID- 26201277
TI  - The Effect of Titanium Surface Modifications on Dental Implant Osseointegration.
AB  - The use of titanium dental implants has consistently changed the way of
      rehabilitating patients in modern dentistry and can count on high long-term
      survival and success rates. With respect to its introduction in the late 1960s,
      clinical indications for implant therapy have been significantly extended and
      optimal results have been achieved, even in clinical conditions formerly
      considered as unfavourable. Such evolution owes a lot to the significant progress
      made in the field of titanium surfaces. The topographical and chemical
      modification of traditional titanium surfaces has led to a real epochal shift in
      implant dentistry. Depending on the type and characteristics of the surface
      treatment applied, a wide range of implants has been produced, which have
      contributed to the success but also increased the risk of confusion in implant
      selection criteria for the clinician. This chapter, which provides an updated
      analysis of the relevant literature, the characteristics of modern implant
      surfaces, the biological principles underlying their role in promoting
      osseointegration and the scientific evidence about their clinical use are
      analyzed and presented.

PMID- 26201278
TI  - Global Gene Expression Analysis for the Assessment of Nanobiomaterials.
AB  - Using global gene expression analysis, the effects of biomaterials and
      nanomaterials can be analyzed at the genetic level. Even though information
      obtained from global gene expression analysis can be useful for the evaluation
      and design of biomaterials and nanomaterials, its use for these purposes is not
      widespread. This is due to the difficulties involved in data analysis. Because
      the expression data of about 20,000 genes can be obtained at once with global
      gene expression analysis, the data must be analyzed using bioinformatics. A
      method of bioinformatic analysis called gene ontology can estimate the kinds of
      changes on cell functions caused by genes whose expression level is changed by
      biomaterials and nanomaterials. Also, by applying a statistical analysis
      technique called hierarchical clustering to global gene expression data between a
      variety of biomaterials, the effects of the properties of materials on cell
      functions can be estimated. In this chapter, these theories of analysis and
      examples of applications to nanomaterials and biomaterials are described.
      Furthermore, global microRNA analysis, a method that has gained attention in
      recent years, and its application to nanomaterials are introduced.

PMID- 26201279
TI  - Membranes for Periodontal Regeneration--A Materials Perspective.
AB  - Periodontitis is a chronic inflammatory disorder affecting nearly 50% of adults
      in the United States. If left untreated, it can lead to the destruction of both
      soft and mineralized tissues that constitute the periodontium. Clinical
      management, including but not limited to flap debridement and/or curettage, as
      well as regenerative-based strategies with periodontal membranes associated or
      not with grafting materials, has been used with distinct levels of success.
      Unquestionably, no single implantable biomaterial can consistently guide the
      coordinated growth and development of multiple tissue types, especially in very
      large periodontal defects. With the global aging population, it is extremely
      important to find novel biomaterials, particularly bioactive membranes and/or
      scaffolds, for guided tissue (GTR) and bone regeneration (GBR) to aid in the
      reestablishment of the health and function of distinct periodontal tissues. This
      chapter offers an update on the evolution of biomaterials (i.e. membranes and
      bioactive scaffolds) as well as material-based strategies applied in periodontal
      regeneration. The authors start by providing a brief summary of the histological
      characteristics and functions of the periodontium and its main pathological
      condition, namely periodontitis. Next, a review of commercially available GTR/GBR
      membranes is given, followed by a critical appraisal of the most recent advances
      in the development of bioactive materials that enhance the chance for clinical
      success of periodontal tissue regeneration.

PMID- 26201280
TI  - Biomaterials in the Reconstruction of the Oral and Maxillofacial Region.
AB  - Reconstruction of maxillofacial bones has proven to be complex due to the
      aesthetic requirements and functional demands of the jaw. Although autogenous
      bone grafts and a wide range of biomaterials are routinely used for facial bone
      reconstruction, these methods are associated with a number of drawbacks,
      including the limited availability of autogenous grafts and the morbidity
      associated with bone graft harvesting, whilst biomaterials are also linked with a
      high failure rate. These limitations have inspired the search for innovative
      techniques for bone bioengineering and the development of more reliable
      biomaterials. Tissue engineering approaches yield powerful tools for long-term
      satisfying results enabling customized reconstruction and the support of natural
      healing processes. There is no doubt that further advances in tissue engineering
      are essential to achieve reliable and satisfactory clinical outcomes for
      patients. This chapter will highlight the clinical application of biomaterials
      and provide an overview of the current scientific concepts in the field.

PMID- 26201281
TI  - Enhanced sputter yields of ion irradiated Au nano particles: energy and size
      dependence.
AB  - Hexagonally arranged Au nanoparticles exhibiting a broad Gaussian-shaped size
      distribution ranging from 30 nm to 80 nm were deposited on Si substrates and
      irradiated with Ar(+) and Ga(+) ions with various energies from 20 to 350 keV and
      1 to 30 keV, respectively. The size and energy dependence of the sputter yield
      were measured using high-resolution scanning electron microscopy image analysis.
      These results were compared to simulation results obtained by iradina, a Monte
      Carlo code, which takes the specifics of the nano geometry into account. The
      experimental sputter yields are significantly higher than simulated sputter
      yields for both bulk and the nano geometry. The difference can be clearly
      attributed to thermally driven effects, which significantly increase the measured
      sputter yields. 

PMID- 26201282
TI  - Flow cytometry quality requirements for monitoring of minimal disease in plasma
      cell myeloma.
AB  - Current therapeutic approaches for plasma cell myeloma (PCM) attain an overall
      survival of more than 6 years for the majority of newly diagnosed patients.
      However, PFS and OS are the only accepted FDA clinical endpoints for
      demonstrating drug efficacy before they can be become frontline therapeutic
      options. There is, however, recognition that the increasing gap between drug
      development and approval for mainstream therapeutic use needs to be shortened. As
      such regulatory bodies such as the FDA are now considering whether biomarker
      response evaluation, as in measurement of minimal residual disease (MRD) as
      assessed by flow cytometry (FC), can provide an early, robust prediction of
      survival and therefore improve the drug approval process. Recently, FC MRD using
      a standardized eight-color antibody methodology has been shown to have a minimum
      sensitivity of 0.01% and an upper sensitivity of 0.001%. To ensure that all
      laboratories using this approach achieve the same levels of sensitivity it is
      crucially important to have standardized quality management procedures in place.
      This manuscript accompanies those published in this special issue and describes
      the minimum that is required for validating and quality monitoring of this highly
      specific test to ensure any laboratory, irrespective of location, will achieve
      the expected quality standards required.

PMID- 26201283
TI  - Low-dose alemtuzumab in refractory/relapsed chronic lymphocytic leukemia: Genetic
      profile and long-term outcome from a single center experience.
AB  - Relapsed/refractory chronic lymphocytic leukemia (CLL) represents a clinical
      challenge, in particular when high risk gene mutations occur. In this setting,
      alemtuzumab was recognized to be effective. This retrospective study evaluates
      long-term efficacy and tolerability of low-dose alemtuzumab in
      relapsed/refractory CLL and correlates clinical outcome with biological feature.
      Sixty-two consecutive patients (median age 68 years) were evaluated; alemtuzumab
      was administered 30 mg weekly for up to 18 weeks. Among the patients included in
      the analysis, 37% were fludarabine-refractory, 33.3% carried a TP53 disruption,
      14.8% a NOTCH1 mutation and 9% a SF3B1 mutation. Overall response rate (ORR) was
      61.3% (complete remission 25.8%). After a median follow-up of 43 months, overall
      survival (OS) and progression free survival (PFS) were 43.1 and 15 months,
      respectively; while ORR was 77.8% for patients carrying TP53 disruptions (OS 33.8
      months) and 43.5% for fludarabine-refractory patients (OS 30 months). Noteworthy,
      long-term survivors (OS >= 36 months) were 54.8%. None of the biological poor
      risk factors negatively impacted on ORR, PFS and OS. Grade >=3 cytopenia occurred
      in 24.2% patients, 6.5% experienced a grade >=3 non-CMV infection and no grade
      >=3 CMV-event occurred. In conclusion, low dose-alemtuzumab is safe and effective
      in relapsed/refractory CLL, also in a long-term follow-up and high-risk genetic
      subgroups.

PMID- 26201284
TI  - Accuracy and the effect of possible subject-based confounders of magnitude-based
      MRI for estimating hepatic proton density fat fraction in adults, using MR
      spectroscopy as reference.
AB  - PURPOSE: To determine the accuracy and the effect of possible subject-based
      confounders of magnitude-based magnetic resonance imaging (MRI) for estimating
      hepatic proton density fat fraction (PDFF) for different numbers of echoes in
      adults with known or suspected nonalcoholic fatty liver disease, using MR
      spectroscopy (MRS) as a reference. MATERIALS AND METHODS: In this retrospective
      analysis of 506 adults, hepatic PDFF was estimated by unenhanced 3.0T MRI, using
      right-lobe MRS as reference. Regions of interest placed on source images and on
      six-echo parametric PDFF maps were colocalized to MRS voxel location. Accuracy
      using different numbers of echoes was assessed by regression and Bland-Altman
      analysis; slope, intercept, average bias, and R2 were calculated. The effect of
      age, sex, and body mass index (BMI) on hepatic PDFF accuracy was investigated
      using multivariate linear regression analyses. RESULTS: MRI closely agreed with
      MRS for all tested methods. For three- to six-echo methods, slope, regression
      intercept, average bias, and R2 were 1.01-0.99, 0.11-0.62%, 0.24-0.56%, and 0.981
      0.982, respectively. Slope was closest to unity for the five-echo method. The two
      echo method was least accurate, underestimating PDFF by an average of 2.93%,
      compared to an average of 0.23-0.69% for the other methods. Statistically
      significant but clinically nonmeaningful effects on PDFF error were found for
      subject BMI (P range: 0.0016 to 0.0783), male sex (P range: 0.015 to 0.037), and
      no statistically significant effect was found for subject age (P range: 0.18
      0.24). CONCLUSION: Hepatic magnitude-based MRI PDFF estimates using three, four,
      five, and six echoes, and six-echo parametric maps are accurate compared to
      reference MRS values, and that accuracy is not meaningfully confounded by age,
      sex, or BMI.

PMID- 26201285
TI  - Effectiveness and safety of short-stay units in the emergency department: a
      systematic review.
AB  - OBJECTIVES: Overcrowding is a serious and ongoing challenge in Canadian hospital
      emergency departments (EDs) that has been shown to have negative consequences for
      patient outcomes. The American College of Emergency Physicians recommends
      observation/short-stay units as a possible solution to alleviate this problem.
      However, the most recent systematic review assessing short-stay units shows that
      there is limited synthesized evidence to support this recommendation; it is over
      a decade old and has important methodologic limitations. The aim of this study
      was to conduct a more methodologically rigorous systematic review to update the
      evidence on the effectiveness and safety of short-stay units, compared with usual
      care, on hospital and patient outcomes. METHODS: A literature search was
      conducted using MEDLINE, the Cochrane Library, Embase, ABI/INFOM, and EconLit
      databases and gray literature sources. Randomized controlled trials of ED short
      stay units (stay of 72 hours or less) were compared with usual care (i.e., not
      provided in a short-stay unit), for adult patients. Risk-of-bias assessments were
      conducted. Important decision-making (gradable) outcomes were patient outcomes,
      quality of care, utilization of and access to services, resource use, health
      system-related outcomes, economic outcomes, and adverse events. RESULTS: Ten
      reports of five studies were included, all of which compared short-stay units
      with inpatient care. Studies had small sample sizes and were collectively at a
      moderate risk of bias. Most outcomes were only reported by one study and the
      remaining outcomes were reported by two to four studies. No deaths were reported.
      Three of the four included studies reporting length of stay found a significant
      reduction among short-stay unit patients, and one of the two studies reporting
      readmission rates found a significantly lower rate for short-stay unit patients.
      All four economic evaluations indicated that short-stay units were a cost-saving
      intervention compared to inpatient care from both hospital and health care system
      perspectives. Results were mixed for outcomes related to quality of care and
      patient satisfaction. CONCLUSIONS: Insufficient evidence exists to make
      conclusions regarding the effectiveness and safety of short-stay units, compared
      with inpatient care.

PMID- 26201286
TI  - Keeping it together: Pulmonary alveoli are maintained by a hierarchy of cellular
      programs.
AB  - The application of in vivo genetic lineage tracing has advanced our understanding
      of cellular mechanisms for tissue renewal in organs with slow turnover, like the
      lung. These studies have identified an adult stem cell with very different
      properties than classically understood ones that maintain continuously cycling
      tissues such as the intestine. A portrait has emerged of an ensemble of cellular
      programs that replenish the cells that line the gas exchange (alveolar) surface,
      enabling a response tailored to the extent of cell loss. A capacity for
      differentiated cells to undergo direct lineage transitions allows for local
      restoration of proper cell balance at sites of injury. We present these recent
      findings as a paradigm for how a relatively quiescent tissue compartment can
      maintain homeostasis throughout a lifetime punctuated by injuries ranging from
      mild to life-threatening, and discuss how dysfunction or insufficiency of
      alveolar repair programs produce serious health consequences like cancer and
      fibrosis. 

PMID- 26201288
TI  - Effect of spinach aqueous extract on wound healing in experimental model diabetic
      rats with streptozotocin.
AB  - BACKGROUND: Chronic ulcer is still a serious issue for diabetic patients.
      Diabetes is a prevalent cause of ulcer regeneration delay and (or) disruption.
      Since Spinacia oleracea extract contains compounds with anti-oxidative and anti
      inflammatory effects, this may be effective in accelerating the healing process
      of ulcers, especially diabetic ulcers. Hence, this study examined the effect of
      Spinacia oleracea aqueous extract on ulcer regeneration in an experimental animal
      model. RESULTS: Macroscopic examination of the wounds of the control group and
      spinach aqueous extract group between 7 and 21 days compared with diabetic group,
      significant changes were observed (P < 0.05). On microscopic examination,
      epithelial tissue formation, formation of granulation tissue and new blood
      vessels in the spinach aqueous extract group and non-diabetic group compared to
      the diabetic group showed significant improvements (P < 0.05). Also, significant
      differences in vascular endothelial growth factor were observed between groups on
      days 3 and 7 (P < 0.05). CONCLUSION: The Spinacia oleracea aqueous extract can be
      effective in regenerating diabetic ulcers. It affects the speed and structure of
      the ulcer. (c) 2015 Society of Chemical Industry.

PMID- 26201287
TI  - Protein Extraction by Means of Electroporation from E. coli with Preserved
      Viability.
AB  - Extracting proteins by means of electroporation from different microorganisms is
      gaining on its importance, as electroporation is a quick, chemical-free, and cost
      effective method. Since complete cell destruction (to obtain proteins)
      necessitates additional work, and cost of purifying the end-product is high,
      pulses have to be adjusted in order to prevent total disintegration. Namely,
      total disintegration of the cell releases bacterial membrane contaminants in the
      final sample. Therefore, our goal was to study different electric pulse
      parameters in order to extract as much proteins as possible from E. coli
      bacteria, while preserving bacterial viability. Our results show that by
      increasing electric field strength the concentration of extracted proteins
      increases and viability reduces. The correlation is reasonable, since high
      electric field destroys bacterial envelope, releasing all intracellular
      components into surrounding media. The strong correlation was also found with
      pulse duration. However, at longer pulses we obtained more proteins, while
      bacterial viability was not as much affected. Pulse number and/or pulse
      repetition frequency at our conditions have no or little effect on concentration
      of extracted proteins and/or bacterial viability. We can conclude that the most
      promising pulse protocol for protein extraction by means of electroporation based
      on our experience would be longer pulses with lower pulse amplitude assuring high
      protein yield and low effect on bacterial viability. 

PMID- 26201289
TI  - Prior Distributions of Material Parameters for Bayesian Calibration of Growth and
      Remodeling Computational Model of Abdominal Aortic Wall.
AB  - For the accurate prediction of the vascular disease progression, there is a
      crucial need for developing a systematic tool aimed toward patient-specific
      modeling. Considering the interpatient variations, a prior distribution of model
      parameters has a strong influence on computational results for arterial
      mechanics. One crucial step toward patient-specific computational modeling is to
      identify parameters of prior distributions that reflect existing knowledge. In
      this paper, we present a new systematic method to estimate the prior distribution
      for the parameters of a constrained mixture model using previous biaxial tests of
      healthy abdominal aortas (AAs). We investigate the correlation between the
      estimated parameters for each constituent and the patient's age and gender;
      however, the results indicate that the parameters are correlated with age only.
      The parameters are classified into two groups: Group-I in which the parameters
      ce, ck1, ck2, cm2,Ghc, and phie are correlated with age, and Group-II in which
      the parameters cm1, Ghm, G1e, G2e, and alpha are not correlated with age. For the
      parameters in Group-I, we used regression associated with age via linear or
      inverse relations, in which their prior distributions provide conditional
      distributions with confidence intervals. For Group-II, the parameter estimated
      values were subjected to multiple transformations and chosen if the transformed
      data had a better fit to the normal distribution than the original. This
      information improves the prior distribution of a subject-specific model by
      specifying parameters that are correlated with age and their transformed
      distributions. Therefore, this study is a necessary first step in our group's
      approach toward a Bayesian calibration of an aortic model. The results from this
      study will be used as the prior information necessary for the initialization of
      Bayesian calibration of a computational model for future applications. 

PMID- 26201290
TI  - Melatonin as a preventive and curative therapy against pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial
      pressure, which leads to right ventricular (RV) hypertrophy and failure. The
      pathophysiological mechanisms of PH remain unclear but oxidative stress is
      believed to contribute to RV dysfunction. Melatonin is a powerful antioxidant and
      is cardioprotective against ischemia-reperfusion injury and hypertension.
      Therefore, we hypothesized that a chronic treatment with melatonin, given as a
      curative or preventive therapy, may confer cardiovascular benefits in PH. PH was
      induced in Long Evans rats (n >= 6 per group), with a single subcutaneous
      injection of monocrotaline (MCT, 80 mg/kg). Melatonin was given daily in the
      drinking water, with the treatment starting either on the day of the injection of
      MCT (dose testing: melatonin 75 ng/L and 6 mg/kg), 14 days after the injection of
      MCT (curative treatment: 6 mg/kg), or 5 days before the injection (preventive
      treatment: 6 mg/kg). The development of PH was assessed by measuring RV
      hypertrophy, RV function, cardiac interstitial fibrosis, and plasma oxidative
      stress. Compared with controls, MCT-treated rats displayed RV hypertrophy and
      dysfunction, increased interstitial fibrosis, and elevated plasma oxidative
      stress. A chronic melatonin treatment (75 ng/L or 6 mg/kg) reduced RV
      hypertrophy, improved RV function and reduced plasma oxidative stress. Curative
      and preventive treatment improved RV functional and plasma oxidative stress
      parameters and reduced cardiac interstitial fibrosis. Our data demonstrate that
      melatonin confers cardioprotection in this model of PH. As melatonin is an
      inexpensive and safe drug, we propose that clinical investigation of the effects
      of melatonin on RV function in patients with PH should be considered. 

PMID- 26201291
TI  - Core needle biopsy could reduce diagnostic surgery in patients with anaplastic
      thyroid cancer or thyroid lymphoma.
AB  - OBJECTIVE: To evaluate the diagnostic performance of fine needle aspiration (FNA)
      and core needle biopsy (CNB) in patients with anaplastic thyroid cancer (ATC) or
      thyroid lymphoma (TL). METHODS: Between January 2000 and March 2012, 104 patients
      were diagnosed with ATC or TL by means of ultrasound (US)-guided FNA, CNB, or
      surgery. This study ultimately included 99 patients with ATC (n = 59) or TL (n =
      40). We evaluated the sensitivity and positive predictive value of FNA and CNB
      for the diagnosis of ATC and TL, and compared the rates of diagnostic surgery
      between FNA and CNB. RESULTS: FNA was used in 83 patients, and CNB was used in 32
      patients initially (n = 16), after FNA results (n = 8), or simultaneously with
      FNA (n = 8). CNB achieved sensitivity of 87.5 % (28/32) and positive predictive
      value of 100.0 % (28/28) for the diagnosis of ATC and TL. The respective values
      for FNA were 50.6 % (40/79) and 90.9 % (40/44). The rate of diagnostic surgery
      was significantly lower after CNB (4/32, 12.5 %) than after FNA (28/79, 35.4 %)
      (p = 0.020). CONCLUSIONS: CNB was able to reduce unnecessary diagnostic surgery
      in patients with ATC or TL by virtue of its superior diagnostic sensitivity and
      positive predictive value compared to FNA. KEY POINTS: * Diagnostic sensitivity
      and PPV for CNB were 87.5 % and 100.0 %, respectively. * The respective values
      for FNA were 50.6 % and 91.0 % for ATC and TL. * Diagnostic surgery rates were
      reduced after CNB compared to FNA (p = 0.020).

PMID- 26201293
TI  - Tubulocystic renal cell carcinoma: a new radiological entity.
AB  - Tubulocystic renal cell carcinoma (TC-RCC) is a recently identified renal
      malignancy. While approximately 100 cases of TC-RCC have been reported in the
      pathology literature, imaging features have not yet been clearly described. The
      purpose of this review is to describe the main radiologic features of this rare
      sub-type of RCC on ultrasound, computed tomography (CT), and magnetic resonance
      imaging (MRI), based jointly on the literature and findings from a multi
      institutional retrospective HIPAA-compliant review of pathology and imaging
      databases. Using a combination of sonographic and CT/MRI features, diagnosis of
      TC-RCC appeared to be strongly suggested in many cases. KEY POINTS: *
      Tubulocystic renal cell carcinoma is a new entity with typical imaging features *
      Diagnosis of tubulocystic renal cell carcinoma can be suggested preoperatively by
      imaging * Cystic renal lesions with high echogenicity may correspond to
      tubulocystic carcinoma.

PMID- 26201292
TI  - Diffusion tensor imaging in patients with obstetric antiphospholipid syndrome
      without neuropsychiatric symptoms.
AB  - OBJECTIVES: To evaluate white matter (WM) integrity in neurologically
      asymptomatic antiphospholipid syndrome (APS) using diffusion tensor imaging (DTI)
      in women with no thrombotic history but with pregnancy loss. METHODS: Imaging was
      performed with a 3 T scanner using structural MRI (T1-weighted, fluid attenuation
      inversion recovery [FLAIR]) and DTI sequences in 66 women with APS and a control
      group of 17 women. Women with APS were further categorized as positive for lupus
      anticoagulant (LA) and/or abeta2GPI-G antibodies (LA/abeta2GPI-G-positive, N =
      29) or negative (LA/abeta2GPI-G-negative, N = 37) for both. Tract-based spatial
      statistics of standard DTI-based indices were compared among groups. RESULTS:
      Women with APS had significantly lower fractional anisotropy (p < 0.05)
      associated with higher mean diffusivity and radial diffusivity compared to the
      control group. There was a stronger association of abnormal DTI features among
      women positive for LA and/or abeta2GPI-IgG antibodies than those who were
      negative. CONCLUSIONS: DTI appears sensitive to subtle WM changes in women with
      APS with no thrombotic history but with pregnancy loss, compatible with
      alterations in axonal structure and in the myelin sheath. The preferential
      association of abnormal DTI features with the two most pathogenic aPLAbs
      reinforces the pathophysiological relevance of our findings. KEY POINTS: * APS
      women exhibited lower FA and higher MD and RD than controls. * WM impairments are
      more severe in patients with positive LA or abeta2GPI-IgG. * An association
      exists between abnormal DTI features and LA or abeta2GPI-IgG positivity. *
      Diffusion tensor imaging detects microstructural white matter abnormalities in
      APS women.

PMID- 26201294
TI  - Clinical indications and radiation doses to the conceptus associated with CT
      imaging in pregnancy: a retrospective study.
AB  - OBJECTIVE: To perform an internal audit at a university hospital with the aim of
      evaluating the number, clinical indication and operating procedure of computed
      tomography (CT) performed on pregnant patients and of estimating the radiation
      doses to the conceptus. METHODS: A retrospective review was conducted of all CT
      examinations performed in a single centre on pregnant patients between January
      2008 and July 2013. The radiation doses to the conceptus were estimated. The
      results were compared with published data. RESULTS: The number of CT examinations
      during pregnancy increased from 3-4 per year in 2008-2011 to 11 per year in 2012.
      The mean estimated conceptus radiation dose was considered negligible for CT of
      the head and cervical spine, being less than 0.01 mGy, and for CT of the chest,
      less than 0.1 mGy. The estimated conceptus radiation dose from abdominopelvic CT
      was on average 28.7 mGy (range 6.7-60.5 mGy). CONCLUSIONS: The number of CT scans
      of pregnant patients increased threefold during the last few years. Most clinical
      indications and doses were in line with good clinical practice and literature;
      only in two cases the dose to the conceptus was higher than 50 mGy. KEY POINTS: *
      An increase in CT imaging of pregnant patients is of concern. * Clinical
      indications were in line with good practice. * Estimated conceptus doses were
      lower or similar to published data. * Internal guidelines for appropriate use of
      imaging during pregnancy should be established.

PMID- 26201295
TI  - Rap2B promotes proliferation, migration, and invasion of human breast cancer
      through calcium-related ERK1/2 signaling pathway.
AB  - Rap2B, a member of GTP-binding proteins, is widely upregulated in many types of
      tumors and promotes migration and invasion of human suprarenal epithelioma.
      However, the function of Rap2B in breast cancer is unknown. Expression of Rap2B
      was examined in breast cancer cell lines and human normal breast cell line using
      Western blot analysis. Using the CCK-8 cell proliferation assay, cell cycle
      analysis, and transwell migration assay, we also elucidated the role of Rap2B in
      breast cancer cell proliferation, migration, and invasion. Results showed that
      the expression of Rap2B is higher in tumor cells than in normal cells. Flow
      cytometry and Western blot analysis revealed that Rap2B elevates the
      intracellular calcium level and further promotes extracellular signal-related
      kinase (ERK) 1/2 phosphorylation. By contrast, calcium chelator BAPTM/AM and MEK
      inhibitor (U0126) can reverse Rap2B-induced ERK1/2 phosphorylation. Furthermore,
      Rap2B knockdown inhibits cell proliferation, migration, and invasion abilities
      via calcium related-ERK1/2 signaling. In addition, overexpression of Rap2B
      promotes cell proliferation, migration and invasion abilities, which could be
      neutralized by BAPTM/AM and U0126. Taken together, these findings shed light on
      Rap2B as a therapeutic target for breast cancer. 

PMID- 26201296
TI  - Informatic nephrology: 17 years of one-center experience.

PMID- 26201297
TI  - Towards deep insight into Ebola virus disease.

PMID- 26201298
TI  - Clinical features and viral kinetics in a rapidly cured patient with Ebola virus
      disease: a case report.
AB  - BACKGROUND: A detailed description of viral kinetics, duration of virus shedding,
      and intraviral evolution in different body sites is warranted to understand Ebola
      virus pathogenesis. Patients with Ebola virus infections admitted to university
      hospitals provide a unique opportunity to do such in-depth virological
      investigations. We describe the clinical, biological, and virological follow-up
      of a case of Ebola virus disease. METHODS: A 43-year-old medical doctor who
      contracted an Ebola virus infection in Sierra Leone on Nov 16, 2014 (day 1), was
      airlifted to Geneva University Hospitals, Geneva, Switzerland, on day 5 after
      disease onset. The patient received an experimental antiviral treatment of
      monoclonal antibodies (ZMAb) and favipiravir. We monitored daily viral load
      kinetics, estimated viral clearance, calculated the half-life of the virus in
      plasma, and analysed the viral genome via high-throughput sequencing, in addition
      to clinical and biological signs. FINDINGS: The patient recovered rapidly,
      despite an initial high viral load (about 1 * 10(7) RNA copies per mL 24 h after
      onset of fever). We noted a two-phase viral decay. The virus half-life decreased
      from about 26 h to 9.5 h after the experimental antiviral treatment. Compared
      with a consensus sequence of June 18, 2014, the isolate that infected this
      patient displayed only five synonymous nucleotide substitutions on the full
      genome (4901A->C, 7837C->T, 8712A->G, 9947T->C, 16201T->C) despite 5 months of
      human-to-human transmission. INTERPRETATION: This study emphasises the importance
      of virological investigations to fully understand the course of Ebola virus
      disease and adaptation of the virus. Whether the viral decay was caused by the
      effects of the immune response alone, an additional benefit from the antiviral
      treatment, or a combination of both is unclear. In-depth virological analysis and
      randomised controlled trials are needed before any conclusion on the potential
      effect of antiviral treatment can be drawn. FUNDING: Geneva University Hospitals,
      Swiss Office of Public Health, Swiss Agency for Development and Cooperation, and
      Swiss National Science Foundation.

PMID- 26201299
TI  - Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus
      nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with
      HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial.
AB  - BACKGROUND: In phase 1 trials, the HIV-1 integrase strand transfer inhibitor
      cabotegravir (GSK1265744) was well tolerated, both alone, and in combination with
      the non-nucleoside reverse transcriptase inhibitor rilpivirine. We assessed
      cabotegravir plus rilpivirine, as a two-drug oral antiretroviral regimen, for the
      maintenance of viral suppression in antiretroviral-naive HIV-1-infected
      individuals. METHODS: In the phase 2b Long-Acting antireTroviral Treatment
      Enabling (LATTE) trial, a multicentre study done in Canada and the USA,
      antiretroviral-naive HIV-1-infected adults (aged >=18 years) were randomly
      allocated in a 1:1:1:1 ratio to oral cabotegravir 10 mg once a day, 30 mg once a
      day, 60 mg once a day, or oral efavirenz 600 mg once a day with dual nucleoside
      reverse transcriptase inhibitors (NRTIs) for 24 weeks of induction. Patients who
      were virologically suppressed by week 24 received a two-drug maintenance regimen
      consisting of their randomly allocated cabotegravir dose plus oral rilpivirine 25
      mg or continued efavirenz plus NRTIs for an additional 72 weeks. Patients and
      investigators were masked to doses of cabotegravir received for 96 weeks, but not
      to the assignment of cabotegravir or efavirenz. The primary endpoint was the
      proportion of patients with fewer than 50 copies per mL of HIV-1 RNA (US Food and
      Drug Administration snapshot algorithm) at week 48. Analysis was by intention to
      treat. This study is registered with ClinicalTrials.gov, NCT01641809. FINDINGS:
      Of 243 patients randomly allocated and treated, 156 (86%) of 181 patients in the
      cabotegravir groups (52 [87%] of 60, 51 [85%] of 60, and 53 [87%] of 61 patients
      in the 10 mg, 30 mg, and 60 mg groups, respectively) and 46 (74%) of 62 in the
      efavirenz group had fewer than 50 copies per mL of HIV-1 RNA after induction
      therapy. After patients in the cabotegravir groups were changed over from dual
      NRTIs to rilpivirine at week 24, 149 (82%; 95% CI 77-88) patients in the
      cabotegravir groups (48 [80%; 70-90], 48 [80%; 70-90], and 53 [87%; 78-95]
      patients in the 10 mg, 30 mg, and 60 mg groups, respectively) versus 44 (71%; 60
      82) in the efavirenz group were virologically suppressed at week 48, and 137
      (76%; 69-82) receiving cabotegravir (41 [68%; 57-80], 45 [75%; 64-86], and 51
      [84%; 74-93] patients in the 10 mg, 30 mg, and 60 mg groups, respectively) versus
      39 (63%; 51-75) in the efavirenz group were virologically suppressed at week 96.
      Treatment-related adverse events were reported by 93 (51%) cabotegravir-treated
      patients (28 [47%], 32 [53%], and 33 [54%] patients in the 10 mg, 30 mg, and 60
      mg groups, respectively) and 42 (68%) efavirenz-treated patients. Six (3%)
      patients in the cabotegravir groups (one [2%], one [2%], and four [7%] patients
      in the 10 mg, 30 mg, and 60 mg groups, respectively) withdrew because of
      treatment-emergent adverse events compared with nine (15%) in the efavirenz
      group. INTERPRETATION: Cabotegravir plus dual NRTI therapy had potent antiviral
      activity during the induction phase. As a two-drug maintenance therapy,
      cabotegravir plus rilpivirine provided antiviral activity similar to efavirenz
      plus dual NRTIs until the end of week 96. Combined efficacy and safety results
      lend support to our selection of oral cabotegravir 30 mg once a day for further
      assessment. LATTE precedes studies of the assessment of longacting injectable
      formulations of both drugs as a two-drug regimen for the treatment of HIV-1
      infection. FUNDING: ViiV Healthcare and Janssen Research and Development.

PMID- 26201300
TI  - Human papillomavirus in young women with Chlamydia trachomatis infection 7 years
      after the Australian human papillomavirus vaccination programme: a cross
      sectional study.
AB  - BACKGROUND: The national quadrivalent human papillomavirus (4vHPV) vaccination
      programme was launched in Australia in April, 2007. In this study, we aimed to
      explore the prevalence of vaccine-targeted human papillomavirus (HPV) types
      contained in the 4vHPV and nine-valent HPV (9vHPV) vaccines detected in young
      women diagnosed with chlamydia. METHODS: In this cross-sectional study, we
      identified specimens from women aged 25 years or younger who attended the
      Melbourne Sexual Health Centre (Melbourne, VIC, Australia) diagnosed with
      chlamydia. We calculated the prevalence of 4vHPV types (6, 11, 16, and 18) and
      the extra five 9vHPV types (31, 33, 45, 52, and 58 alone) excluding 4vHPV types,
      stratified by Australian financial year (and according to the prevaccination and
      postvaccination periods) and self-reported vaccination status, for all women,
      Australian-born women, Australian-born women aged 21 years and younger, and
      overseas-born women. We calculated adjusted prevalence ratios using binomial log
      linear regression. FINDINGS: Between July 1, 2004, and June 30, 2014, we included
      1202 women. The prevalence of 4vHPV types in Australian-born women decreased
      during this period (HPV 6 and 11: 2004-05 nine [16%, 95% CI 8-28] of 56 vs 2013
      14 one [2%, 0-9] of 57, p<0.0001; HPV 16 and 18: 17 [30%, 19-44] vs two [4%, 0
      12], p<0.0001). In Australian-born women aged 21 years and younger, HPV 6 and 11
      prevalence remained at 0% for all years after 2008-09, and we detected HPV 16 and
      18 in 5% or less of samples for the same period. In unvaccinated Australian-born
      women, we noted a significant decrease in 4vHPV types from 66 (41%, 95% CI 34-49)
      of 160 in the prevaccination period (from July 1, 2004, to June 30, 2007) to five
      (19%, 6-38) of 27 in the postvaccination period (July 1, 2007, to June 30, 2014;
      p=0.031), but not in the 9vHPV types, excluding 4vHPV (36 [23%, 95% CI 16-30] vs
      seven [26%, 11-46]; p=0.805). INTERPRETATION: The three-dose vaccination coverage
      was sufficient for the 4vHPV types to almost disappear in Australian-born women
      aged 21 years or younger within 3 years of introduction of the national HPV
      vaccination programme. We noted strong herd protection, with a significant
      decrease in the prevalence of 4vHPV in unvaccinated women. The 4vHPV vaccination
      programme in Australia has been successful at protecting women against 4vHPV
      types. FUNDING: Australian National Health and Medical Research Council.

PMID- 26201301
TI  - Near full control of human papillomavirus vaccine types.

PMID- 26201302
TI  - The LATTE study: a provocative brew.

PMID- 26201303
TI  - Photochemical degradation of imazosulfuron under simulated California rice field
      conditions.
AB  - BACKGROUND: The photodegradation of imazosulfuron (IMZ), a potent broad-spectrum
      herbicide, was investigated under simulated rice field conditions. Previous
      reports have indicated that it is photolabile, but have failed to report
      radiation intensity or determine a quantum yield, precluding extrapolation to
      environmental rates. Therefore, the objective of this investigation was to
      determine the photolytic rate of IMZ under simulated rice field conditions and
      how it is influenced by environmental factors such as turbidity, salinity and
      temperature. RESULTS: IMZ was efficiently photolyzed in all solutions and fitted
      pseudo-first-order kinetics. Degradation was faster in HPLC-grade water than in
      field water. Field-relevant variances in temperature, turbidity and salinity did
      not significantly influence degradation. The experimentally derived quantum yield
      for direct photolysis (2.94 * 10(3) ) was used to predict the half-life of IMZ in
      a California rice field (3.6 days). CONCLUSIONS: Aqueous photolysis is predicted
      to be an important process in the overall degradation of IMZ in the environment,
      regardless of variances in salinity, organic matter and temperature. Based on the
      predicted half-life of IMZ in a California rice field (3.6 days), state-mandated
      holding periods for field water post-IMZ application (30 days) are expected to
      allow for sufficient clearance of the herbicide (>98%), preventing significant
      contamination of the environment upon release of tailwater. (c) 2015 Society of
      Chemical Industry.

PMID- 26201304
TI  - Social Information Processing in Anger Expression and Partner Violence in
      Returning U.S. Veterans.
AB  - We examined social information processing factors that could represent pathways
      through which posttraumatic stress disorder (PTSD) symptoms relate to anger
      expression and intimate partner violence (IPV) perpetration in returning U.S.
      veterans. The sample included 92 male Operation Enduring Freedom/Operation Iraqi
      Freedom veterans, primarily Caucasian (77.4%), with smaller numbers of African
      American, Asian, Hispanic or Latino, American Indian or Alaskan Native, and other
      minority participants (9.7%, 2.2%, 2.2%, 3.2%, and 5.3% respectively). The
      average age was 40.37 (SD = 9.63) years. Data were collected through self-report
      questionnaires (PTSD Checklist, State-Trait Anger Expression Scale, Revised
      Conflict Tactics Scales) and the Articulated Thoughts in Simulated Situations
      experimental protocol. Laboratory-based assessment of cognitive biases and
      hostile attributions were tested as mediators of associations between PTSD
      symptoms and anger expression and IPV. Among the PTSD symptom clusters,
      hyperarousal symptoms were most strongly associated with anger expression (r =
      .50) and IPV perpetration (r = .27). Cognitive biases mediated associations
      between PTSD total scores and 3 of 4 PTSD cluster scores as well as anger
      expression. Hostile attribution biases were also associated with IPV perpetration
      (r = .23). We discuss the implications of these findings for understanding social
      information processing mechanisms for the relationship between PTSD symptoms and
      aggression.

PMID- 26201305
TI  - Effects of allergic rhinitis and desloratadine on the submandibular gland in a
      rat allergy model.
AB  - BACKGROUND: Allergic rhinitis (AR) and antihistamine usage can cause xerostomia.
      The study aims to examine if AR, antihistamines, and the use of antihistamines in
      AR have histopathological effects on the submandibular gland. The study also
      investigates the effect of oxidant and antioxidant plasma parameters. METHODS:
      Thirty-two adult Sprague-Dawley rats were used in the study. The rats were
      divided into the 4 following groups: the control group (C group); the AR group;
      an antihistamine-treated group (AH group); and an AR plus antihistamine-treated
      group (AR+AH group). The AR and AR+AH groups were sensitized using ovalbumin. The
      AR+AH and AH groups received desloratadine. The histopathological effects of AR
      and desloratadine treatment on the submandibular glands (SMGs) and the values of
      the oxidative and antioxidative serum parameters were evaluated. RESULTS:
      Histopathological examination of sections of the SMGs from the AR and AH groups
      revealed that vacuolization was present in the mucous acinar and ductal cells and
      that the number of connective-tissue cells was greater than that of the control
      group. The appearances of the AR+AH-group sections were similar to those of the
      control group. The superoxide dismutase activity level and the glutathione level
      were relatively decreased in these groups compared with those of the control
      group. The malondialdehyde level in the AR group was increased compared with that
      of the control group. CONCLUSION: The AR-induced pathological changes were
      diminished by desloratadine treatment. Thus, the new-generation antihistamine
      desloratadine may be used to treatment of AR patients who have xerostomia.

PMID- 26201306
TI  - Population Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) in Preterm
      and Term Neonates: Model Development and External Evaluation.
AB  - OBJECTIVES: The aims of this study were to develop a population pharmacokinetic
      model for intravenous paracetamol in preterm and term neonates and to assess the
      generalizability of the model by testing its predictive performance in an
      external dataset. METHODS: Nonlinear mixed-effects models were constructed from
      paracetamol concentration-time data in NONMEM 7.2. Potential covariates included
      body weight, gestational age, postnatal age, postmenstrual age, sex, race, total
      bilirubin, and estimated glomerular filtration rate. An external dataset was used
      to test the predictive performance of the model through calculation of bias,
      precision, and normalized prediction distribution errors. RESULTS: The model
      building dataset included 260 observations from 35 neonates with a mean
      gestational age of 33.6 weeks [standard deviation (SD) 6.6]. Data were well
      described by a one-compartment model with first-order elimination. Weight
      predicted paracetamol clearance and volume of distribution, which were estimated
      as 0.348 L/h (5.5 % relative standard error; 30.8 % coefficient of variation) and
      2.46 L (3.5 % relative standard error; 14.3 % coefficient of variation),
      respectively, at the mean subject weight of 2.30 kg. An external evaluation was
      performed on an independent dataset that included 436 observations from 60
      neonates with a mean gestational age of 35.6 weeks (SD 4.3). The median
      prediction error was 10.1 % [95 % confidence interval (CI) 6.1-14.3] and the
      median absolute prediction error was 25.3 % (95 % CI 23.1-28.1). CONCLUSIONS:
      Weight predicted intravenous paracetamol pharmacokinetics in neonates ranging
      from extreme preterm to full-term gestational status. External evaluation
      suggested that these findings should be generalizable to other similar patient
      populations.

PMID- 26201308
TI  - Impulse Control and Callous-Unemotional Traits Distinguish Patterns of
      Delinquency and Substance Use in Justice Involved Adolescents: Examining the
      Moderating Role of Neighborhood Context.
AB  - Both callous-unemotional (CU) traits and impulse control are known risk factors
      associated with delinquency and substance use. However, research is limited in
      how contextual factors such as neighborhood conditions influence the associations
      between these two dispositional factors and these two externalizing behaviors.
      The current study utilized latent class analysis (LCA) to identify unique classes
      of delinquency and substance use within an ethnically diverse sample (n = 1216)
      of justice-involved adolescents (ages 13 to 17) from three different sites.
      Neighborhood disorder, CU traits, and impulse control were all independently
      associated with membership in classes with more extensive histories of
      delinquency and substance use. The effects of CU traits and impulse control in
      distinguishing delinquent classes was invariant across levels of neighborhood
      disorder, whereas neighborhood disorder moderated the association between impulse
      control and substance use. Specifically, the probability of being in more severe
      substance using classes for those low in impulse control was stronger in
      neighborhoods with fewer indicators of social and physical disorder. 

PMID- 26201307
TI  - Pharmacokinetic Aspects of Vascular Endothelial Growth Factor Tyrosine Kinase
      Inhibitors.
AB  - Scientists have identified the impact of angiogenesis on tumor growth and
      survival. Among other efficient drugs, several small-molecule tyrosine kinase
      inhibitors (TKIs) targeting the vascular endothelial growth factor receptor
      (VEGFR) have been developed and have already been integrated into the treatment
      of various advanced malignancies. This review provides a compilation of current
      knowledge on the pharmacokinetic aspects of all VEGFR-TKIs already approved by
      the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA)
      and of those still under investigation. Additional information on substance
      metabolism, potential for drug-drug interactions (DDIs), and the need for dose
      adaptation in patients with predominant renal and/or hepatic impairment has been
      included. All TKIs introduced in this review were administered orally, allowing
      for easy drug handling for healthcare professionals and patients. For almost all
      substances, the maximum plasma concentrations were reached within a short period
      of time. The majority of the substances showed a high plasma protein binding and
      their excretion occurred via the feces and, to a lesser extent, via the urine. In
      most cases, dose adaptation in patients with mild to moderate renal or hepatic
      impairment is not recommended. Cytochrome P450 (CYP) 3A4 was found to play a
      crucial role in the drug metabolic processes of many compounds. In order to
      prevent unwanted DDIs, co-administration of VEGFR TKIs together with CYP3A4
      inhibitors or inducers should be avoided. Throughout all TKIs, the data indicate
      high inter-individual variability. The causes of this are still unclear and
      require further research to allow for individualization of treatment regimens. 

PMID- 26201309
TI  - Study of microRNAs (miRNAs) that are predicted to target the autoantigens Ro/SSA
      and La/SSB in primary Sjogren's Syndrome.
AB  - The elevated tissue expression of Ro/SSA and La/SSB autoantigens appears to be
      crucial for the generation and perpetuation of autoimmune humoral responses
      against these autoantigens in Sjogren's syndrome (SS). The mechanisms that govern
      their expression are not known. miRNAs, the post-transcriptional regulators of
      gene expression, might be implicated. We have identified previously the miRNAs
      let7b, miR16, miR181a, miR200b-3p, miR200b-5p, miR223 and miR483-5p that are
      predicted to target Ro/SSA [Ro52/tripartite motif-containing protein 21 (TRIM21),
      Ro60/TROVE domain family, member 2 (TROVE2)] and La/SSB mRNAs. To study possible
      associations with autoantigen mRNA expression and disease features, their
      expression was investigated in minor salivary gland (MSG) tissues, peripheral
      blood mononuclear cells (PBMC) and long-term cultured non-neoplastic salivary
      gland epithelial cells (SGEC) from 29 SS patients (20 of 29 positive for
      autoantibodies to Ro/SSA and La/SSB) and 24 sicca-complaining controls. The
      levels of miR16 were up-regulated in MSGs, miR200b-3p in SGECs and miR223 and
      miR483-5p in PBMCs of SS patients compared to sicca-complaining controls. The MSG
      levels of let7b, miR16, miR181a, miR223 and miR483-5p were correlated positively
      with Ro52/TRIM21-mRNA. miR181a and miR200b-3p were correlated negatively with
      Ro52/TRIM21 and Ro60/TROVE2 mRNAs in SGECs, respectively, whereas let7b, miR200b
      5p and miR223 associated with La/SSB-mRNA. In PBMCs, let7b, miR16, miR181a and
      miR483-5p were correlated with Ro52/TRIM21, whereas let7b, miR16 and miR181a were
      also associated with La/SSB-mRNA expression. Significantly lower miR200b-5p
      levels were expressed in SS patients with mucosa-associated lymphoid tissue
      (MALT) lymphoma compared to those without. Our findings indicate that miR16,
      miR200b-3p, miR223 and miR483-5p are deregulated in SS, but the exact role of
      this deregulation in disease pathogenesis and autoantigen expression needs to be
      elucidated.

PMID- 26201310
TI  - New and emerging biologic therapies for moderate-to-severe plaque psoriasis:
      mechanistic rationales and recent clinical data for IL-17 and IL-23 inhibitors.
AB  - The development of effective and well-tolerated biologic therapies has advanced
      the management of psoriasis by enabling clinicians to treat underlying disease
      mechanisms. Biologics approved for the treatment of moderate-to-severe psoriasis
      include three tumor necrosis factor alpha inhibitors and an interleukin
      12/interleukin-23 inhibitor. The establishment of the immunological basis of
      psoriasis has led to the development of biologic agents targeting specific
      downstream mediators in the psoriatic cascade. These drugs inhibit cytokines and
      cytokine signaling/transcription mediators like interleukin-17, which plays an
      important role in immunopathogenesis. Several interleukin-17 inhibitors are
      undergoing phase 3 clinical studies. In addition, biologics that selectively
      inhibit interleukin-23 have been assessed in phase 2 studies. This review
      describes how the dissection of pathways in the immunopathogenesis of psoriasis
      has led to the development of therapeutic agents and highlights the latest
      clinical efficacy, safety and tolerability data on new and emerging biologic
      therapies that selectively target interleukin-17 or interleukin-23. 

PMID- 26201312
TI  - Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium
      competitive acid blocker, vs. lansoprazole for the treatment of erosive
      oesophagitis.
AB  - BACKGROUND: The potassium-competitive acid blocker vonoprazan (VPZ) has potent
      acid-inhibitory effects and may offer clinical advantages over conventional
      therapy for acid-related disorders. AIM: To investigate the efficacy and safety
      of VPZ in patients with erosive oesophagitis (EO). METHODS: In this multicentre,
      randomised, double-blind, parallel-group, dose-ranging study, patients >=20 years
      with endoscopically confirmed EO [Los Angeles (LA) grades A-D] received VPZ 5,
      10, 20 or 40 mg, or lansoprazole (LPZ) 30 mg once daily for 8 weeks. The primary
      endpoint was the proportion of healed EO subjects as shown by endoscopy at week
      4. RESULTS: A total of 732 subjects received VPZ or LPZ. The proportion of healed
      EO subjects at week 4 was 92.3%, 92.5%, 94.4%, 97.0% and 93.2%, respectively,
      with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. All VPZ doses were non-inferior to
      LPZ when adjusted for baseline LA grades A/B and C/D. Among those with LA grades
      C/D, the proportions of healed EO subjects were 87.3%, 86.4%, 100%, 96.0% and
      87.0%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. The incidence of
      adverse events was similar across the groups. CONCLUSIONS: Vonoprazan was
      effective and non-inferior to LPZ in healing EO. VPZ 20 mg or higher was highly
      efficacious for severe EO (LA grades C/D). VPZ was associated with no safety
      concern during this 8-week study, while there was a dose-dependent increase in
      serum gastrin. Once-daily VPZ 20 mg is the recommended clinical dose for treating
      EO.

PMID- 26201313
TI  - HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to
      evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the
      placebo-controlled portion of a phase 2 adalimumab study.
AB  - BACKGROUND: Determining treatment response for patients with hidradenitis
      suppurativa (HS) can be challenging due to limitations of current disease
      activity evaluations. OBJECTIVE: Evaluate the novel, validated endpoint,
      Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility as an outcome
      measure. METHODS: Patients with baseline total abscess and inflammatory nodule
      count (AN count) of at least three and draining fistula count of 20 or fewer
      comprised the post hoc subpopulation analysed. HiSCR (at least a 50% reduction in
      total AN count, with no increase in abscess count, and no increase in draining
      fistula count relative to baseline) and HS-PGA Response [Hidradenitis Suppurativa
      Physician's Global Assessment score of clear, minimal, or mild, with at least a 2
      grade improvement from baseline] were used to evaluate patient response after
      adalimumab treatment weekly, every other week, or placebo (1 : 1 : 1). RESULTS:
      The subpopulation included 132 (85.7%) patients; 70.5% women and 73.5% white. At
      week 16, HiSCR was achieved by 54.5% receiving weekly adalimumab, 33.3% every
      other week, and 25.6% placebo and HS-PGA Response was achieved by 20.5% receiving
      weekly adalimumab, 6.7% every other week and 2.3% placebo. CONCLUSION: HiSCR was
      more responsive to change than HS-PGA Response in this subpopulation.

PMID- 26201314
TI  - Selecting clinical diagnoses: logical strategies informed by experience.
AB  - This article describes reasoning strategies used by clinicians in different
      diagnostic circumstances and how these modes of inquiry may allow further insight
      into the evaluation and treatment of patients. Specifically, it aims to make
      explicit the implicit logical considerations that guide a variety of strategies
      in the diagnostic process, as exemplified in specific clinical cases. It focuses,
      in particular, in strategies that clinicians use to move from a large set of
      possible diagnoses initially suggested by abductive inferences - the process of
      hypothesis generation that creates a diagnostic space - to a narrower set or even
      to a single 'best' diagnosis, where the criteria to determine what is 'best' may
      differ according to different strategies. Experienced clinicians should have a
      diversified kit of strategies - for example, Bayesian probability or inference to
      a lovely explanation - to select from among previously generated hypotheses,
      rather than rely on any one approach every time. 

PMID- 26201315
TI  - Primary renal squamous cell carcinoma mimicking the renal cyst: a case report and
      review of the recent literature.
AB  - BACKGROUND: Renal squamous cell carcinoma is a rare neoplasm with poor prognosis.
      Chronic irritation from nephrolithiasis and/or pyelonephritis is the leading
      cause. CASE PRESENTATION: We described a 51-year-old male patient who was
      admitted because of left flank pain. Ultrasonography showed a renal cyst
      containing calculus. However, contrast-enhanced ultrasonography and CT scan
      revealed an irregular-shaped mass derived from a calculi-containing cyst.
      Ultrasound guided biopsy confirmed the diagnosis of renal squamous cell
      carcinoma. The patient refused any further therapeutic management and died six
      months later. CONCLUSIONS: Our present case emphasizes that the careful
      diagnostic work-up and use of multiple imaging modalities in cases of unusual
      renal calculi is quite necessary, since they may carry the risk of co-existing
      hidden malignancy.

PMID- 26201317
TI  - Foreword to the proceedings of the 8th international ALPD symposium, New Delhi,
      India, November 15-17, 2013.

PMID- 26201316
TI  - Analysis of influenza transmission in the households of primary and junior high
      school students during the 2012-13 influenza season in Odate, Japan.
AB  - BACKGROUND: Households are one of the major settings of influenza transmission in
      the community and transmission is frequently initiated by school-aged children.
      We surveyed households with primary school (PS) and/ or junior high school (JH)
      children for the 2012-13 influenza season in Odate, Japan then characterized the
      epidemiology of influenza household transmission as well as estimated the serial
      intervals. METHODS: We delivered a self-reported questionnaire survey to
      households with PS and/or JH school children in Odate City, Japan. Influenza A
      (H3N2) virus predominantly circulated during the 2012-13 influenza season. We
      investigated the epidemiological characteristics of within-household transmission
      and calculated the serial intervals (SI). SIs were drew by a non-parametric model
      and compared with parametric models by the Akaike Information Criterion. The
      covariable contributions were investigated by the accelerated failure model.
      RESULTS: Household influenza transmission was identified in 255 out of 363
      household respondents. Primary school (PS) children accounted for 45.1 % of
      primary cases, and disease transmission was most commonly observed between PS
      children and parents, followed by transmission from PS children to siblings. In
      primary cases of PS or JH children, younger age and longer absence from school
      were significantly associated with household transmission events. The mean SI was
      estimated as 2.8 days (95 % confidence interval 2.6-3.0 days) in the lognormal
      model. The estimated acceleration factors revealed that while secondary school
      age and the absence duration > 7 days were associated with shorter and longer
      SIs, respectively, antiviral prescriptions for primary cases made no
      contribution. CONCLUSIONS: High frequencies of household transmission from
      primary school with shorter SI were found. These findings contribute to the
      development of future mitigation strategies against influenza transmission in
      Japan.

PMID- 26201318
TI  - Alcohol, TLR4-TGF-beta antagonism, and liver cancer.
AB  - Alcohol abuse and obesity are two known risk factors for hepatocellular carcinoma
      (HCC) that also synergistically promote HBV/HCV-related carcinogenesis. TLR4, the
      receptor for endotoxin, participates in inflammatory processes such as M1
      activation of hepatic macrophages in alcoholic liver disease. However, its role
      in liver carcinogenesis via ectopic expression and activation has only recently
      been revealed in alcohol/HCV-associated HCC models. Alcohol feeding to mice
      expressing the HCV Ns5a in a hepatocyte specific manner aggravates liver
      inflammation via activation of overexpressed TLR4 in the parenchymal cells. Long
      term alcohol feeding produces liver tumors in these transgenic mice in a manner
      dependent on TLR4. From these mice, CD133+/CD49f+ tumor-initiating stem cell-like
      cells (TICs) have been isolated. These TICs exhibit self-renewal and tumorigenic
      activities driven by TLR4-dependent upregulation of the stem cell factor NANOG. A
      defective TGF-beta tumor suppressor pathway is identified in the TICs and
      mediated by NANOG target genes Igf2bp3 and Yap1. This TGF-beta pathway antagonism
      is responsible in part for the TICs' tumorigenic activity and chemoresistance.
      Conversely, mice with an attenuated TGF-beta pathway due to haploinsufficiency of
      beta2-Spectrin, spontaneously develop liver tumors and alcohol feeding increases
      tumor incidence in a TLR4-dependent manner. This reciprocal antagonism between
      TLR4 and TGF-beta pathways may serve as a novel therapeutic target for HCC. 

PMID- 26201319
TI  - Novel modulators of hepatosteatosis, inflammation and fibrogenesis.
AB  - Alcoholic steatosis, instead of being innocuous, plays a critical role in liver
      inflammation and fibrogenesis. The severity of fatty liver is governed by the
      concerted balance between lipid transport, synthesis, and degradation. Whereas
      scavenger receptor class B, type I (SR-B1) is critical for reverse cholesterol
      uptake by the liver, peroxisome proliferator-activated receptor-gamma (PPARgamma)
      coactivator-1alpha and -beta (PGC1alpha and PGC1beta) are critical for lipid
      degradation and synthesis, respectively. Because betaine is a lipotropic agent,
      we have evaluated its effects on alcoholic steatosis. Betaine effectively
      prevented chronic alcohol-mediated (i) impaired SR-B1 glycosylation, plasma
      membrane localization, and consequent impaired cholesterol transport; and (ii) up
      regulation of PGC-1beta, sterol regulatory element-binding protein 1c and
      downstream lipogenic genes with concomitant increased liver cholesterol,
      triglycerides and hepatic lipid score. Similarly, because of its anti
      inflammatory and anti-fibrotic effects in other organs, we evaluated the
      protective effects of thymosin beta4 (Tbeta4) against carbon tetrachloride (CCl4)
      induced hepatotoxicity in rat. Tbeta4 prevented CCl4-induced (i) necrosis,
      inflammatory infiltration and up-regulation of alpha1(2)collagen, alpha-smooth
      muscle actin (alpha-SMA), platelet derived growth factor beta (PDGF-beta)
      receptor and fibronectin mRNA expression; (ii) down-regulation of adipogenic
      gene, PPARgamma and the up-regulation of epigenetic repressor gene, methyl CpG
      binding protein 2 (MeCP2) mRNA levels, suggesting that the anti-fibrogenic
      actions of Tbeta4 involve the prevention of trans-differentiation of quiescent
      hepatic stellate cells into myo-fibroblasts largely by up-regulating PPARgamma
      and by down-regulating MeCP2 genes. We therefore conclude that betaine and Tbeta4
      can effectively protect against alcoholic hepatosteatosis and hepatic
      fibrogenesis, respectively. 

PMID- 26201320
TI  - Epigenetic histone modifications in a clinically relevant rat model of chronic
      ethanol-binge-mediated liver injury.
AB  - PURPOSE: Ethanol binge augments liver injury after chronic ethanol consumption in
      humans, but the mechanism behind the enhanced liver injury by ethanol binge is
      not known. In this study we used a clinically relevant rat model in which liver
      injury is amplified by binge after chronic ethanol treatment and investigated the
      importance of histone modifications. METHODS: Eight-week-old Sprague-Dawley rats
      were fed ethanol in a liquid diet for 4 weeks. Control rats were fed an
      isocaloric liquid diet. This was followed by three binge administrations of
      ethanol (intragastric 5 g/kg body weight, 12 h apart). In the control, ethanol
      was replaced by water. Four hours after the last binge administration, liver
      samples were analyzed for histone modifications and parameters of liver injury.
      RESULTS: Chronic ethanol administration alone caused an increase in histone H3
      ser10 and ser28 (H3S10 or S28) phosphorylation, and binge ethanol reduced their
      levels. Levels of dually modified phosphoacetylated histone H3 (H3AcK9/PS10)
      increased after acute binge ethanol and remained same after chronic ethanol
      binge. In contrast, histone H3 lysine-9 acetylation (H3AcK9) was not increased
      after chronic ethanol but increased significantly after acute binge and chronic
      ethanol binge. Increase in histone acetylation was accompanied by increased
      phospho-ERK1/2 in the nuclear extracts. Increased acetylation after chronic
      ethanol binge was also accompanied by increased protein levels of GCN5 histone
      acetyl transferase and a modest increase in HDAC3 in the nucleus. Histone lysine
      9 dimethylation was significantly increased after chronic ethanol binge. Chronic
      ethanol binge also resulted in a decrease in the SAM:SAH ratio with a relative
      decrease of SAM levels and a corresponding increase in SAH levels. CONCLUSIONS:
      Ethanol binge after chronic ethanol altered the profile of site-specific histone
      modifications and may underlie the mechanism of augmented liver injury by chronic
      ethanol-binge-treated rats.

PMID- 26201321
TI  - Erratum to: Epigenetic histone modifications in a clinically relevant rat model
      of chronic ethanol-binge-mediated liver injury.

PMID- 26201322
TI  - Hepatocyte-mediated cytotoxicity and host defense mechanisms in the alcohol
      injured liver.
AB  - The consumption of alcohol is associated with many health issues including
      alcoholic liver disease (ALD). The natural history of ALD involves the
      development of steatosis, inflammation (steatohepatitis), fibrosis and cirrhosis.
      During the stage of steatohepatitis, the combination of inflammation and cellular
      damage can progress to a severe condition termed alcoholic hepatitis (AH).
      Unfortunately, the pathogenesis of AH remains uncharacterized. Some modulations
      have been identified in host defense and liver immunity mechanisms during AH that
      highlight the role of intrahepatic lymphocyte accumulation and associated
      inflammatory cytokine responses. Also, it is hypothesized that alcohol-induced
      injury to liver cells may significantly contribute to the aberrant lymphocytic
      distribution that is seen in AH. In particular, the regulation of lymphocytes by
      hepatocytes may be disrupted in the alcoholic liver resulting in altered
      immunologic homeostasis and perpetuation of disease. In recent studies, it was
      demonstrated that the direct killing of activated T lymphocytes by hepatocytes is
      facilitated by the asialoglycoprotein receptor (ASGPR). The ASGPR is a well
      characterized glycoprotein receptor that is exclusively expressed by hepatocytes.
      This hepatic receptor is known for its role in the clearance of desialylated
      glycoproteins or cells, yet neither its physiological function nor its role in
      disease states has been determined. Interestingly, alcohol markedly impairs ASGPR
      function; however, the effect alcohol has on ASGPR-mediated cytotoxicity of
      lymphocytes remains to be elucidated. This review discusses the contribution of
      hepatocytes in immunological regulation and, importantly, how pathological
      effects of ethanol disrupt hepatocellular-mediated defense mechanisms. 

PMID- 26201323
TI  - Immunity and inflammatory signaling in alcoholic liver disease.
AB  - The pathogenesis of alcoholic liver disease (ALD) is multifactorial and
      characterized by steatosis, steatohepatitis and cirrhosis. Several signaling
      pathways in different liver cell types that contribute to the development and
      progression of alcoholic liver injury have been identified. Among these, immune
      cells and signaling pathways are the most prominent and central to ALD. Both
      innate and adaptive immune responses contribute to ALD. The key features of
      inflammatory pathways in ALD including liver innate and adaptive immune cell
      types, signaling receptors/pathways, and pro- and antiinflammatory/protective
      responses are summarized here. 

PMID- 26201325
TI  - Organ dysfunctions in patients with alcoholic cirrhosis.

PMID- 26201324
TI  - Recent insights into hepatic cancer stem cells.
AB  - It has been suggested that the development of hepatocellular carcinoma (HCC) is
      related to the existence of cancer stem cells (CSCs) or tumor-initiating cells.
      Although CSCs populations may be recognized by use of stem cell markers and/or
      their functional capacities, their profiles might be diverse, because of the
      heterogeneity of HCC among individuals. Recent studies indicate that activation
      of CSCs is related to dysregulation of crucial molecular signaling pathways able
      to alter the intrinsic properties of normal stem cells. This short review
      describes the latest evidence of the presence of CSCs, alteration of several
      developmental and oncogenic pathways, CSC-related microRNAs, and drug resistance
      in HCC. This information may aid the development of potential novel therapy
      targeting CSCs in HCC. 

PMID- 26201326
TI  - Bacterial infections in cirrhosis.
AB  - Bacterial infections occur in 25-35 % of cirrhotics admitted to hospital. Health
      care associated and hospital acquired (nosocomial) infections are the most common
      epidemiology, with community acquired infections less common (15-30 %).
      Spontaneous bacterial peritonitis and urinary infections are the most common
      sites, with spontaneous bacteremia, pneumonia, cellulitis and other sites being
      less common. The risk of infection is increased among subjects with more severe
      liver disease and an infection in the past 6 months. Bacteria are isolated from
      approximately half of patients with a clinical diagnosis of infection. Gram
      negative enterobacteriaceae are the most common organisms among community
      acquired infections; Gram-positive cocci are the most common organisms isolated
      among subjects with nosocomial infections. Up to 30 % of hospital associated
      infections are with multidrug resistant bacteria. Consequently, empiric
      antibiotic therapy that is recommended for community acquired infections is often
      inadequate for nosocomial infections. Infections worsen liver function. In
      hospital and 1-year mortality of cirrhotics with infections is significantly
      higher than among cirrhotics without infection. In-hospital complications of
      infections, such as severe sepsis and septic shock, and mortality, are increased
      among subjects with multidrug-resistant infections as compared with cirrhotics
      with susceptible bacteria. Short-term antibiotic prophylaxis of cirrhotics with
      upper gastrointestinal bleeding and long-term antibiotic prophylaxis of selected
      cirrhotics with spontaneous bacterial peritonitis reduces infections and improves
      survival. Albumin administration to cirrhotics with SBP and evidence of advanced
      liver disease improves survival. The benefit of albumin administration to
      cirrhotics with infections other than SBP is under investigation. 

PMID- 26201327
TI  - New drug targets for alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) represents a spectrum of disorders, ranging from
      simple steatosis to severe alcoholic hepatitis and cirrhosis. The severe form of
      ALD comprises multiple problems in the liver, including inflammation,
      hepatocellular damage, fibrosis, and impaired liver regeneration, and likely
      requires combinational therapies. In this review, we discuss recently identified
      therapeutic targets that inhibit inflammation, ameliorate hepatocyte death, and
      promote liver repair in ALD, with a focus on our recent studies on the
      immunosuppressive drug prednisolone and the hepatoprotective cytokine interleukin
      22. Clinical trials examining prednisolone plus interleukin-22 therapy for severe
      alcoholic hepatitis are currently under consideration. 

PMID- 26201328
TI  - Liver transplantation for alcoholic hepatitis. Current situation and future.
AB  - Alcoholic hepatitis (AH) is a life-threatening disease, especially in its severe
      forms, with a 30-40 % mortality rate at 1 month in the absence of treatment.
      Severe forms are traditionally defined by Maddrey discriminant function >32.
      Until now, only corticosteroids have provided a significant benefit to survival
      in severe AH patients. Non-responders to corticosteroid therapy can be identified
      after 7 days of treatment when the Lille score is above 0.45, and this concerns
      about 40 % of patients with AH. With so few therapeutic alternatives for severe
      AH, the debate on liver transplantation (LT) has reopened. However, the latter
      indication for LT is facing several difficulties such as the 6-month abstinence
      rule ordinarily required for alcoholic diseases, risk of alcohol relapse and
      comprehensive fear of a drop in donations. Inversely, transplanted AH patients
      have a significantly improved survival, and an excess risk of alcohol relapse has
      not been demonstrated. Solutions can certainly be found in order to improve
      severe AH survival without causing a loss of opportunity for LT for other
      indications by good selection according to strict criteria. 

PMID- 26201329
TI  - Basis of HBV persistence and new treatment options.
AB  - The majority of the morbidity and mortality associated with hepatitis B virus
      infection is due to viral persistence and its consequences. The heterogeneity of
      outcomes from HBV infection suggests that both viral and host factors influence
      the development of chronic infection. Study of host genetic susceptibility has
      revealed a number of genes including MHC class II loci and cytokine receptors,
      which decrease the risk of persistence. On the viral side, the replication system
      is adapted to generate high levels of virions without stimulating the innate
      immune system. Secreted viral proteins (HBsAg and HBeAg) suppress innate
      responses through inhibition of TLR signaling, which leads to a weak adaptive
      immune response with an exhausted phenotype that is incapable of inducing viral
      elimination. However, even when the adaptive immune system begins to take effect
      after HBe seroconversion, the ability of the virus to mutate and evade T and B
      cell-mediated responses helps to sustain persistent infection. Understanding the
      mechanisms of persistence is important for the design of therapeutic strategies.
      Although there are currently no specific drugs that target the viral
      minichromosome (cccDNA), it is expected that in the future we will be able to use
      existing drugs more effectively to eliminate the infection. 

PMID- 26201330
TI  - Efficacy of iron chelator deferoxamine for hepatic arterial infusion chemotherapy
      in advanced hepatocellular carcinoma patients refractory to current treatments.
AB  - The prognosis of advanced hepatocellular carcinoma (HCC) remains poor. For
      patients with advanced HCC, the multikinase inhibitor sorafenib is recommended as
      the current standard of care. In contrast, hepatic arterial infusion chemotherapy
      (HAIC) is one of the recommended treatments in Japan. However, in Japan, the use
      of sorafenib versus hepatic arterial infusion chemotherapy for first-line
      treatment remains unclear, because there have been no randomized controlled
      trials comparing HAIC with sorafenib. HAIC can substantially prolong survival in
      patients with complete and partial response, while non-responders may be suitable
      candidates for sorafenib therapy. Nonetheless, HAIC non-responders with
      deteriorated liver function currently have no treatment options. We have shown
      the efficacy of an alternative therapy, the iron chelator deferoxamine, for
      advanced HCC patients with deteriorated liver function. Iron chelators may have
      future therapeutic possibilities in this patient population. 

PMID- 26201331
TI  - Immune therapy for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related
      death worldwide. Currently, there are no treatment options available for a large
      number of these patients. One of the mechanisms that may contribute to tumor
      growth is the lack of an effective immune response toward viral antigens or other
      tumor-associated antigens (TAAs). Immunotherapy has been tested as a potential
      therapeutic option for these patients. Several methods of immune modulation for
      augmenting antitumor immunity are being explored and have been shown to be
      effective in suppressing HCC growth in animal models. Activation of HCC-specific
      response can be accomplished by targeting hepatitis B or C viral antigens, alpha
      fetoprotein, or other TAAs. This review summarizes part of the recent data on the
      use of adoptive transfer of immunity against viral antigens, oral immune
      modulation against TAAs, and the use of pulsed innate immune cells and gut
      adjuvants for the suppression of HCC; it reviews some additional new
      immunotherapeutic approaches. 

PMID- 26201332
TI  - Liver dialysis in acute-on-chronic liver failure: current and future
      perspectives.
AB  - Patients with acute-on-chronic liver failure (ACLF) are known to have a very high
      mortality rate as the majority of these patients succumb to multiorgan failure.
      Liver transplant remains the only option for these patients; however, there are
      problems with its availability, cost and also the complications and side effects
      associated with immunosuppression. Unlike advanced decompensated liver disease,
      there is a potential for hepatic regeneration and recovery in patients with ACLF.
      A liver support system, cell or non-cell based, logically is likely to provide
      temporary functional support until the donor liver becomes available or the
      failing liver survives the onslaught of the acute insult and spontaneously
      regenerates. Understanding the pathogenesis of liver failure and regeneration is
      essential to define the needs for a support system. Removal of hepatotoxic
      metabolites and inhibitors of hepatic regeneration by liver dialysis, a non-cell
      based hepatic support, could help to provide a suitable microenvironment and
      support the failing liver. The current systems, i.e., MARS and Prometheus, have
      failed to show survival benefits in patients with ACLF based on which newer
      devices with improved functionality are currently under development. However,
      larger randomized trials are needed to prove whether these devices can enable
      restoration of the complex dysregulated immune system and impact organ failure
      and mortality in these patients. 

PMID- 26201335
TI  - The 22nd Conference of the Asian Pacific Association for the Study of the Liver :
      APASL 2012-Taipei, Taiwan-16-19 February.

PMID- 26201333
TI  - Growth factors enhance liver regeneration in acute-on-chronic liver failure.
AB  - Acute-on-chronic liver failure is a distinct syndrome characterized by a rapid
      progression of liver disease culminating in organ failure and death. The only
      definitive treatment is liver transplantation. However, there is a possible
      element of reversibility and hepatic regeneration if the acute insult can be
      tided over. Exogenously administered growth factors may stimulate hepatocytes,
      hepatic progenitor cells and bone marrow-derived cells to supplement hepatic
      regeneration. The proposed review is intended to provide an in-depth analysis of
      the individual components of hepatic and bone marrow niches and highlight the
      growing role of various growth factors in liver regeneration in health and in
      liver failure. 

PMID- 26201336
TI  - The 22nd Conference of the Asian Pacific Association for the Study of the Liver :
      APASL 2012-Taipei, Taiwan-16-19 February.

PMID- 26201334
TI  - Logical-continuous modelling of post-translationally regulated bistability of
      curli fiber expression in Escherichia coli.
AB  - BACKGROUND: Bacteria have developed a repertoire of signalling mechanisms that
      enable adaptive responses to fluctuating environmental conditions. The formation
      of biofilm, for example, allows persisting in times of external stresses, e.g.
      induced by antibiotics or a lack of nutrients. Adhesive curli fibers, the major
      extracellular matrix components in Escherichia coli biofilms, exhibit
      heterogeneous expression in isogenic cells exposed to identical external
      conditions. The dynamical mechanisms underlying this heterogeneity remain poorly
      understood. In this work, we elucidate the potential role of post-translational
      bistability as a source for this heterogeneity. RESULTS: We introduce a
      structured modelling workflow combining logical network topology analysis with
      time-continuous deterministic and stochastic modelling. The aim is to evaluate
      the topological structure of the underlying signalling network and to identify
      and analyse model parameterisations that satisfy observations from a set of
      genetic knockout experiments. Our work supports the hypothesis that the
      phenotypic heterogeneity of curli expression in biofilm cells is induced by
      bistable regulation at the post-translational level. Stochastic modelling
      suggests diverse noise-induced switching behaviours between the stable states,
      depending on the expression levels of the c-di-GMP-producing (diguanylate
      cyclases, DGCs) and -degrading (phosphodiesterases, PDEs) enzymes and reveals the
      quantitative difference in stable c-di-GMP levels between distinct phenotypes.
      The most dominant type of behaviour is characterised by a fast switching from
      curli-off to curli-on with a slow switching in the reverse direction and the
      second most dominant type is a long-term differentiation into curli-on or curli
      off cells. This behaviour may implicate an intrinsic feature of the system
      allowing for a fast adaptive response (curli-on) versus a slow transition to the
      curli-off state, in line with experimental observations. CONCLUSION: The
      combination of logical and continuous modelling enables a thorough analysis of
      different determinants of bistable regulation, i.e. network topology and
      biochemical kinetics, and allows for an incorporation of experimental data from
      heterogeneous sources. Our approach yields a mechanistic explanation for the
      phenotypic heterogeneity of curli fiber expression. Furthermore, the presented
      work provides a detailed insight into the interactions between the multiple DGC-
      and PDE-type enzymes and the role of c-di-GMP in dynamical regulation of cellular
      decisions.

PMID- 26201337
TI  - The 22nd Conference of the Asian Pacific Association for the Study of the Liver :
      APASL 2012 - Taipei, Taiwan - 16-19 February.

PMID- 26201338
TI  - The 22nd Conference of the Asian Pacific Association for the Study of the Liver :
      APASL 2012-Taipei, Taiwan-16-19 February.

PMID- 26201340
TI  - Different aspects of CD4 T cells that lead to viral clearance or persistence of
      HCV infection.
AB  - More than 170 million people worldwide are infected with hepatitis C virus (HCV).
      A characteristic of this virus is a high tendency toward chronic infection.
      Several factors affect the viral outcome after infection. Among them, HCV
      specific CD4 T cells are thought to play a crucial role in controlling viremia.
      Cumulative data showed that spontaneously resolved individuals have vigorous CD4
      T-cell responses to a broad spectrum of HCV antigens and maintain these responses
      over a long period of time, whereas chronically infected patients lose their CD4
      T-cell responses in the acute phase of infection. Although several possibilities
      of why CD4 T cells lose their function have been proposed, the mechanisms are not
      completely understood. Moreover, there is another subset of CD4 T cells called
      regulatory T cells (Tregs). These cells suppress immune reaction of T cells, B
      cells, and antigen-presenting cells, and are thought to protect organs from
      immune overreaction and autoimmunity. An increasing amount of data supports the
      possibility that Tregs participate in the mechanism of HCV persistence. It is
      obvious that CD4 T cells are the main effectors controlling HCV outcome. To
      achieve a better prognosis, we need to understand the mechanism of how HCV earns
      its chronicity by escaping from host cellular immune attacks. In this review, we
      will focus on the role of HCV-specific T cells in controlling viremia,
      particularly the aspects of these cells being either inhibitors or propellers of
      chronic infection. 

PMID- 26201341
TI  - IL28B, HCV core mutations, and hepatocellular carcinoma: does host genetic make
      up shape viral evolution in response to immunity?
AB  - Mutations in the core sequence of the HCV genome have been reported to influence
      treatment response, fibrosis progression, and hepatocarcinogenesis in Asian
      patients with genotype-1 chronic hepatitis C (CHC). In this issue, Miura et al.
      report data consistent with a causal relationship between the R70 -> Q70 core
      variant and hepatocellular carcinoma (HCC) risk in CHC genotype-1b patients, by
      the prospective evaluation of changes in the consensus sequence in the entire
      open reading frame between treatment failure and HCC development or end of follow
      up, and validation of the initial findings in a confirmatory cohort. Furthermore,
      they observed an association between the IL28B genotype, which is believed to
      influence the immune response to viral infection, and the direction of time
      dependent changes in core residue 70, with unfavorable IL28B genotypes linked to
      a preferential shift to the 70Q associated with HCC. Although this association
      needs to be validated in independent cohorts, and IL28B variants did not
      influence HCC risk, these results suggest that IL28B genotype might not only
      influence the behavior of the innate immune system in the presence of HCV
      genotype-1 infection but also shape the resultant viral evolution, with possible
      consequences on major clinical outcomes, such as HCC development, and treatment
      response. 

PMID- 26201342
TI  - Establishment and validation of a simple noninvasive model to predict significant
      liver fibrosis in patients with chronic hepatitis B.
AB  - BACKGROUND: There have been still few valuable noninvasive models that can be
      used as indirect markers of liver fibrosis in chronic hepatitis B (CHB)
      infection. METHODS: In 374 patients with chronic hepatitis B virus infection, the
      correlation between the conventional parameters and significant fibrosis
      confirmed by liver biopsy was assessed using univariate analysis and logistic
      regression. A model was established and assessed by the receiver operating
      characteristic (ROC) curves. Then it was validated in 108 prospectively enrolled
      patients. A part of the patients were followed up with cirrhosis as the end
      point, using survival analysis to assess the prognostic value of the model.
      RESULTS: A model named AIAG was constructed consisting of age, international
      normalized ratio, albumin, and gamma-glutamyltransferase which could discriminate
      between CHB patients with and without significant fibrosis. The area under ROC
      curves was 0.842 (95% CI, 0.795-0.888) for the training group (n = 250) and 0.806
      (95% CI, 0.730-0.882) for the validation group (n = 124). In the training group,
      using a cut-off score of <0.32, the presence of significant fibrosis could be
      excluded with high accuracy (90% negative predictive value); similarly, applying
      a cut-off score of >0.72, the presence of significant fibrosis could be correctly
      identified with high accuracy (93% positive predictive value). Similar results
      have been shown in the internal and external validation groups. In the follow-up
      study, we found that the AIAG score may have good prognostic values to predict
      the progression of clinically overt cirrhosis in CHB patients. CONCLUSIONS: AIAG,
      a simple marker panel consisting of conventional parameters, could easily predict
      significant fibrosis with a high degree of accuracy.

PMID- 26201344
TI  - In Vitro Evaluation of pH Responsive Doxazosin Loaded Mesoporous Silica
      Nanoparticles: A Smart Approach in Drug Delivery.
AB  - OBJECTIVE: To develop a pH responsive drug delivery system (DDS) for controlled
      release of therapeutic cargo, Doxazosin Mesylate (DZM) which was loaded into
      carrier material mesoporous silica nanoparticle (MSN) and subsequently coated
      with Eudragit S-100(ES-100) to release the drug at pH 7.4. MATERIAL AND METHODS:
      We have synthesized cylindrical MSN under acidic condition using non-ionic
      surfactant (Pluronic((r)) P 123) and Tetraethoxysilane (TEOS). After post
      synthesis treatment (PST) surfactant was removed by calcination. To obtain pH
      sensitive release calcined MSN was coated with ES-100 (MSN-DZMES100). The Brauner
      Emmett-Teller (BET) surface area, adsorption isotherm, t-plot, pore volume of MSN
      were done in surface area analyzer to characterize different MSN samples (as
      synthesized, calcined, and coated). RESULT AND DISCUSSION: Highest surafce area
      (427.114 m(2)/g) was observed in case of calcined sample when compared to as
      synthesized (3.1198m(2)/g) and coated MSN (8.8480m(2)/g). Adsorption pore width
      of final coated sample was 12.58 nm whereas as synthesized and calcined samples
      possessed pore width 36.82 nm and 7.32 nm respectively. All uncoated and coated
      MSN samples were further characterized with FESEM, TEM, FTIR. No significant
      interaction between drug and MSN was found from FTIR studies. The drug loading
      into coated mesoporous support was found to be 43.7%. In vitro studies were done
      at different pH using Franz-diffusion cell. Results showed significant release at
      pH 7.4 from MSNDZM- ES100. Cumulative drug release over a period of 10 hr was 81%
      at this systemic pH. CONCLUSION: ES-100 coated mesoporous silica nanoparticle is
      a smart carrier for pH responsive release of guest molecule.

PMID- 26201343
TI  - Comparative assessment of methods for the computational inference of transcript
      isoform abundance from RNA-seq data.
AB  - BACKGROUND: Understanding the regulation of gene expression, including
      transcription start site usage, alternative splicing, and polyadenylation,
      requires accurate quantification of expression levels down to the level of
      individual transcript isoforms. To comparatively evaluate the accuracy of the
      many methods that have been proposed for estimating transcript isoform abundance
      from RNA sequencing data, we have used both synthetic data as well as an
      independent experimental method for quantifying the abundance of transcript ends
      at the genome-wide level. RESULTS: We found that many tools have good accuracy
      and yield better estimates of gene-level expression compared to commonly used
      count-based approaches, but they vary widely in memory and runtime requirements.
      Nucleotide composition and intron/exon structure have comparatively little
      influence on the accuracy of expression estimates, which correlates most strongly
      with transcript/gene expression levels. To facilitate the reproduction and
      further extension of our study, we provide datasets, source code, and an online
      analysis tool on a companion website, where developers can upload expression
      estimates obtained with their own tool to compare them to those inferred by the
      methods assessed here. CONCLUSIONS: As many methods for quantifying isoform
      abundance with comparable accuracy are available, a user's choice will likely be
      determined by factors such as the memory and runtime requirements, as well as the
      availability of methods for downstream analyses. Sequencing-based methods to
      quantify the abundance of specific transcript regions could complement validation
      schemes based on synthetic data and quantitative PCR in future or ongoing
      assessments of RNA-seq analysis methods.

PMID- 26201345
TI  - In vitro Percutaneous Absorption of Niacinamide and Phytosterols and in vivo
      Evaluation of their Effect on Skin Barrier Recovery.
AB  - In this study, we evaluated different strategies to optimize the percutaneous
      absorption of niacinamide (NA) and soy phytosterols (FITO) by making use of solid
      lipid nanoparticles (SLN) and penetration enhancers, such as the hydrogenated
      lecithin. The evaluation of the skin permeation of NA and FITO has been effected
      in vitro using excised human skin (i.e., stratum corneum-epidermis or SCE).
      Furthermore, we evaluated the in vivo effect that NA and FITO has on skin barrier
      recovery after the topical application; using the extent of methyl nicotinate
      (MN)-induced erythema in damaged skin as a parameter to determine the rate of
      stratum corneum recovery. Results pointed out the importance of these strategies
      as valid tools for NA and FITO topical delivery. In fact, soy lecithin based
      formulations were able to increase the percutaneous absorption of the two active
      ingredients, while SLN guaranteed an interesting delayed and sustained release of
      FITO. In vivo evaluation showed clearly that the formulation containing both the
      actives (NA and FITO) is able to recover about 95% of skin barrier integrity
      eight days after tape stripping. This effect is probably due to the "synergistic
      effect" of NA and FITO. 

PMID- 26201346
TI  - The Effect of Hydrophilic and Hydrophobic Structure of Amphiphilic Polymeric
      Micelles on Their Transportation in Rats.
AB  - In the previous study, we have clarified how the hydrophilic and hydrophobic
      structures of amphiphilic polymers impact the transport of their micelles (PEEP
      PCL, PEG-PCL and PEG-DSPE micelles) in epithelial MDCK cells (Biomaterials 2013,
      34: 6284-6298). In this study, we attempt to clarify the behavior of the three
      micelles in rats. Coumarin-6 loaded micelles were injected into different
      sections of intestine of rats and observed by confocal laser scanning microscope
      (CLSM) or orally administrated and conducted pharmacokinetic study. All of the
      three kinds of micelles were able to cross the intestinal epithelial cells and
      enter blood circulation. The PEEP-PCL micelles demonstrated the fastest
      distribution mainly in duodenum, while the PEGDSPE micelles showed the longest
      distribution with the highest proportion in ileum of the three. No significant
      difference was observed among the pharmacokinetic parameters of the three
      micelles. The results were consistent in the two analysis methods mentioned
      above, yet there were some differences between in vivo and in vitro results
      reported previously. It might be the distinction between the environments in MDCK
      model and intestine that led to the discrepancy. The hydrophobicity of
      nanoparticles could both enhance uptake and hinder the transport across the
      mucus. However, there was no intact mucus in MDCK model, which preferred
      hydrophobic nanoparticles. PEEP was the most hydrophilic material constructing
      the micelles in the study and its uptake would be increased in rats compared to
      that in MDCK model, while DSPE was more hydrophobic than the others and MDCK
      model would be more ideal for its uptake. Considering the inconsistency of the
      results in the two models, whether the methods researchers were generally using
      at present were reasonable needs further investigation. 

PMID- 26201347
TI  - Fifteen-minute consultation on limiting investigations in the fainting child.
AB  - Syncope can be a dramatic and frightening experience for the patient and
      onlookers. It can also be a confusing area for doctors, with a lack of diagnostic
      certainty and a differential that ranges from the completely benign to the life
      threatening. This is a tricky area for clinicians, who can find it difficult to
      reassure their patients and their families. The aim of this article is to present
      a clear scheme for appropriate investigation and referral of paediatric patients
      with syncope. The aim of investigations in such cases should be to confirm or
      exclude serious, life-threatening causes of syncope. 

PMID- 26201348
TI  - Comparison of Two LED Light Bulbs to a Dimmable CFL and their Effects on Broiler
      Chicken Growth, Stress, and Fear.
AB  - The poultry industry is currently undergoing a shift to alternative lighting
      sources as incandescent lights become less available. While LED and CFL bulbs
      both have associated increased energy savings, they may affect the bird's growth
      and well-being differently as they output different light spectrums. To determine
      how different LED bulbs and a CFL bulb affected broiler performance, behavior,
      stress, and overall well-being, we conducted an experiment using Cobb broiler
      chickens (N=360). A NextGen LED bulb (NextGen), a Once Innovations LED bulb
      (Once), and a dimmable CFL (CFL) were used, all of which had different spectral
      outputs. Growth and feed conversion, several stress measures, fear tests, organ
      characteristics, and animal welfare assessment parameters were collected to
      determine how each light type affected animal well-being. LED treatments had
      shorter (P<0.05) latency to right during tonic immobility testing when compared
      to the CFL treatment; however, no other differences (P>0.05) were seen in the
      other fear tests. The Once treatment resulted in lower composite physical
      asymmetry, heterophil/lymphocyte ratio, and basal plasma corticosterone
      concentrations compared to the other treatments (P<0.05). Differences were
      observed in some organ measures; notably in the eye dimensions of the Once
      treatment. The Once treatment also had lower (P<0.05) plumage, hock, and footpad
      scores when compared to CFL treatment, while the Nextgen treatment had lower
      (P<0.05) plumage and hock scores than the CFL treatment but no difference between
      the two was seen in foot pad scores. Weight at the end of the growout was not
      affected by bulb type, however, both LED treatments had increased feed conversion
      (P<0.05). These results indicate that LEDs can result in better well-being and
      feed conversion when compared to CFLs. It is also notable that the LEDs did not
      have the same effects and this is likely due to the spectrum of light each
      creates. LEDs were shown to improve production and well-being of broiler chickens
      compared to CFLs.

PMID- 26201349
TI  - Need for a proactive and structured approach to risk analysis when designing
      phase I trials.

PMID- 26201350
TI  - Delays in healthcare delivery to sick neonates in Enugu South-East Nigeria: an
      analysis of causes and effects.
AB  - BACKGROUND: In most parts of the world, neonatal mortality rates have shown a
      slower decline when compared with under-5 mortality decline. A sick newborn can
      die within minutes if there is a delay in presentation, thus early diagnosis and
      treatment are essential for the survival of a critically ill newborn. This study
      investigated factors responsible for delays in healthcare services for the sick
      newborn and maternal socio-demographic variables that influence these delays in
      Enugu, South-East Nigeria. METHODS: This was a community-based descriptive study.
      A total of 376 respondents were randomly selected from 4 of the 17 local
      government areas of Enugu State. Mothers and/or caregivers that were nursing or
      had nursed a child in the previous 2 years were enrolled. Self-reported data on
      delays encountered during healthcare for sick newborn were collected using
      pretested structured questionnaire. Chi-square and multivariate logistic
      regression were used to determine the association between causes of delays in
      newborn healthcare services, maternal socio-demographics and relationships with
      newborn mortality. RESULTS: Delays in reaching healthcare facilities accounted
      for the most common delays encountered by respondents, 78.0%, in this study,
      followed by delays at household level, 24.2% and delays at health facility level
      16.0% (P = 0.000). Mothers with knowledge of >=3 WHO recognized danger signs
      compared with those with <=2 were significantly less likely to delay at household
      (level 1: 40.7 versus 59.3%) (P = 0.017) and reaching healthcare service (level
      2: 19.9 versus 80.1%) (P = 0.028). Delays at health facility level (level 3)
      occurred more at tertiary health facilities (59.0%), secondary health facilities
      (39.1%) and primary healthcare facilities (19.7%) compared with private health
      facilities (13.5%) (P = 0.000). CONCLUSIONS: Delays in seeking healthcare at all
      levels especially those related to transporting the sick newborn to the hospital
      are a contributor to newborn mortality in Nigeria. Improving access to healthcare
      could potentially reduce mortality in the sick newborn.

PMID- 26201351
TI  - Improved in vivo performance of amperometric oxygen (PO2) sensing catheters via
      electrochemical nitric oxide generation/release.
AB  - A novel electrochemically controlled release method for nitric oxide (NO) (based
      on electrochemical reduction of nitrite ions) is combined with an amperometric
      oxygen sensor within a dual lumen catheter configuration for the continuous in
      vivo sensing of the partial pressure of oxygen (PO2) in blood. The on-demand
      electrochemical NO generation/release method is shown to be fully compatible with
      amperometric PO2 sensing. The performance of the sensors is evaluated in rabbit
      veins and pig arteries for 7 and 21 h, respectively. Overall, the NO releasing
      sensors measure both venous and arterial PO2 values more accurately with an
      average deviation of -2 +/- 11% and good correlation (R(2) = 0.97) with in vitro
      blood measurements, whereas the corresponding control sensors without NO release
      show an average deviation of -31 +/- 28% and poor correlation (R(2) = 0.43) at
      time points >4 h after implantation in veins and >6 h in arteries. The NO
      releasing sensors induce less thrombus formation on the catheter surface in both
      veins and arteries (p < 0.05). This electrochemical NO generation/release method
      could offer a new and attractive means to improve the biocompatibility and
      performance of implantable chemical sensors. 

PMID- 26201352
TI  - The contribution of co-reference resolution to supervised relation detection
      between bacteria and biotopes entities.
AB  - BACKGROUND: The acquisition of knowledge about relations between bacteria and
      their locations (habitats and geographical locations) in short texts about
      bacteria, as defined in the BioNLP-ST 2013 Bacteria Biotope task, depends on the
      detection of co-reference links between mentions of entities of each of these
      three types. To our knowledge, no participant in this task has investigated this
      aspect of the situation. The present work specifically addresses issues raised by
      this situation: (i) how to detect these co-reference links and associated co
      reference chains; (ii) how to use them to prepare positive and negative examples
      to train a supervised system for the detection of relations between entity
      mentions; (iii) what context around which entity mentions contributes to relation
      detection when co-reference chains are provided. RESULTS: We present experiments
      and results obtained both with gold entity mentions (task 2 of BioNLP-ST 2013)
      and with automatically detected entity mentions (end-to-end system, in task 3 of
      BioNLP-ST 2013). Our supervised mention detection system uses a linear chain
      Conditional Random Fields classifier, and our relation detection system relies on
      a Logistic Regression (aka Maximum Entropy) classifier. They use a set of
      morphological, morphosyntactic and semantic features. To minimize false
      inferences, co-reference resolution applies a set of heuristic rules designed to
      optimize precision. They take into account the types of the detected entity
      mentions, and take advantage of the didactic nature of the texts of the corpus,
      where a large proportion of bacteria naming is fairly explicit (although natural
      referring expressions such as "the bacteria" are common). The resulting system
      achieved a 0.495 F-measure on the official test set when taking as input the gold
      entity mentions, and a 0.351 F-measure when taking as input entity mentions
      predicted by our CRF system, both of which are above the best BioNLP-ST 2013
      participant system. CONCLUSIONS: We show that co-reference resolution
      substantially improves over a baseline system which does not use co-reference
      information: about 3.5 F-measure points on the test corpus for the end-to-end
      system (5.5 points on the development corpus) and 7 F-measure points on both
      development and test corpora when gold mentions are used. While this outperforms
      the best published system on the BioNLP-ST 2013 Bacteria Biotope dataset, we
      consider that it provides mostly a stronger baseline from which more work can be
      started. We also emphasize the importance and difficulty of designing a
      comprehensive gold standard co-reference annotation, which we explain is a key
      point to further progress on the task.

PMID- 26201353
TI  - Autocrine motility factor promotes epithelial-mesenchymal transition in
      endometrial cancer via MAPK signaling pathway.
AB  - Autocrine motility factor (AMF) as a cytokine and a growth factor, is known to
      regulate tumor cell growth and motility in the progress of various human
      malignant tumors, however, its role in endometrial cancer (EC) has not been fully
      studied. In the present study, using immunohistochemistry, we found that AMF was
      highly expressed in EC tissues compared with normal endometrial tissues and
      tissue micrioarray technology showed positive correlation between AMF expression
      and epithelial-to-mesenchymal transition (EMT) related markers E-cadherin,
      vimentin and Snail. Next, we detected that silencing of AMF by stable
      transfection with shRNA induced mesenchymal-to-epithelial transition phenotype in
      Ishikawa and HEC-1B cells by qRT-PCR, western blotting and immunofluorescence.
      Gene expression profile revealed that AMF silencing resulted in altered
      expression of EMT related molecular mediators including Snail and transforming
      growth factor beta receptor 1, and involvement of mitogen-activated protein
      kinase (MAPK) signaling pathway. Additionally, we found that EMT related markers
      were downregulated with pretreatment of the MAPK-specific inhibitor U0126 by
      western blotting. The present study is the first to support a role for AMF
      mediating EMT in endometrial cancer through MAPK signaling. Therefore, AMF may
      provide a potential prognostic and therapeutic target in preventing EC
      progression. 

PMID- 26201354
TI  - Volumetric ellipsoid zone mapping for enhanced visualisation of outer retinal
      integrity with optical coherence tomography.
AB  - Objective assessment of retinal layer integrity with optical coherence tomography
      (OCT) is currently limited. The ellipsoid zone (EZ) has been identified as an
      important feature on OCT that has critical prognostic value in macular disorders.
      In this report, we describe a novel assessment tool for EZ integrity that
      provides visual and quantitative assessment across an OCT data set. Using this
      algorithm, we describe the findings in multiple clinical examples, including
      normal controls, age-related macular degeneration, drug effects (eg, ocriplasmin,
      hydroxychloroquine) and effects of surgical manipulation (eg, following membrane
      peeling using intraoperative OCT). EZ mapping provides both en face visualisation
      of EZ integrity and EZ-retinal pigment epithelium height. Additionally,
      volumetric, area and linear measurements are feasible using this assessment tool.

PMID- 26201355
TI  - Mutation analysis of BEST1 in Japanese patients with Best's vitelliform macular
      dystrophy.
AB  - PURPOSE: To describe the clinical and genetic features of Japanese patients with
      Best's vitelliform macular dystrophy (BVMD). PATIENTS AND METHODS: This study
      examined 22 patients, including 16 probands from 16 families with BVMD.
      Comprehensive ophthalmic examinations were performed, including dilated
      funduscopy, full-field electroretinography (ERG) and electro-oculography (EOG).
      BEST1 mutation analysis was performed by Sanger sequencing. RESULTS: All 16
      probands exhibited characteristic BVMD fundus appearances, abnormal EOG, and
      normal ERG responses with the exception of one diabetic retinopathy proband.
      Genetic analysis identified 12 BEST1 variants in 13 probands (81%). Of these, 10
      variants (p.T2A, p.R25W, p.F80L, p.V81M, p.A195V, p.R218H, p.G222E, p.V242M,
      p.D304del and p.E306D) have been previously reported in BVMD, while two variants
      (p.S7N and p.P346H) were novel, putative disease-causing variants. Single BEST1
      variants were found in 12 probands. The one proband with compound heterozygous
      variants (p.S7N and p.R218H) exhibited typical BVMD phenotypes (pseudohypopyon
      stage and vitelliruptive stage in the right and left eyes, respectively).
      CONCLUSIONS: Twelve different variants, two of which (p.S7N and p.P346H) were
      novel, were identified in the 13 Japanese families with BVMD. Compound
      heterozygous variants were found in one proband exhibiting a typical BVMD
      phenotype. Our results suggest that BEST1 variants do play a large role in
      Japanese patients with BVMD.

PMID- 26201356
TI  - An important role of the hepcidin-ferroportin signaling in affecting tumor growth
      and metastasis.
AB  - Epidemiological and experimental studies have suggested that deregulated hepcidin
      ferroportin (FPN) signaling is associated with the increased risk of cancers.
      However, the effects of deregulated hepcidin-FPN signaling on tumor behaviors
      such as metastasis and epithelial to mesenchymal transition (EMT) have not been
      closely investigated. In this study, LL/2 cancer cells were found to exhibit an
      impaired propensity to home into lungs, and a reduced ability to develop tumors
      was also demonstrated in lungs of Hamp1(-/-) mice. Moreover, hepatic hepcidin
      deficiency was found to considerably favor tumor-free survival in Hamp1(-/-)
      mice, compared with wild-type mice. These data thus underscored a contributive
      role of hepatic hepcidin in promoting lung cancer cell homing and fostering tumor
      progression. To explore the role of FPN in regulating tumor progression, we
      genetically engineered 4T1 cells with FPN over-expression upon induction by
      doxycycline. With this cell line, it was discovered that increased FPN expression
      reduced cell division and colony formation in vitro, without eliciting
      significant cell death. Analogously, FPN over-expression impeded tumor growth and
      metastasis to lung and liver in mice. At the molecular level, FPN over-expression
      was identified to undermine DNA synthesis and cell cycle progression.
      Importantly, FPN over-expression inhibited EMT, as reflected by the significant
      decrease of representative EMT markers, such as Snail1, Twist1, ZEB2, and
      vimentin. Additionally, there was also a reduction of lactate production in cells
      upon induction of FPN over-expression. Together, our results highlighted a
      crucial role of the hepcidin-FPN signaling in modulating tumor growth and
      metastasis, providing new evidence to understand the contribution of this
      signaling in cancers. 

PMID- 26201357
TI  - Paper-based cell impedance sensor and its application for cytotoxic evaluation.
AB  - Disposable analytical devices for developing sensitive and label-free monitoring
      of cancerous cells would be attractive for cancer research. Here, paper-based
      electroanalytical devices based on impedance spectrometry were applied for the
      study of K562 cells and the toxic effect of anticancer drugs. The proposed device
      integrating gold nanorods modified ITO electrodes could provide a biocompatible
      surface for immobilization of living cells maintaining their bioactivity. The
      impedance results exhibited good correlation to the logarithmic value of cell
      numbers ranging from 7.5 * 10(2) to 3.9 * 10(6) cells mL(-1) with a detection
      limit of 500 cells mL(-1). Furthermore, this strategy was used to evaluate the
      cytotoxic effects of arsenic trioxide and cyclophosphamide. Results obtained by
      the impedimetric method correlate well with the conventional cell viability
      assay. Cells exposed to drugs exhibited a prominent reduction of impedance data,
      showing an inverse dose-dependent relationship. This simple, cost-effective and
      portable paper-based electrochemical analytical device could provide a new
      impedance platform for applications in monitoring cell behavior, pharmacological
      studies and toxicological analyses.

PMID- 26201358
TI  - [Functional Magnetic Resonance Imaging in Selected Eye Diseases].
AB  - In the study, an actual overview of eyes examinations by means of functional
      magnetic resonance focused on selected eyes diseases is presented. Special
      attention is paid to hypertension glaucomas, normotension glaucoma, age-related
      macular degeneration, and peeling of the epimacular membrane and the internal
      limiting membrane. The authors point out the decreased activity of the visual
      cortex in diseases in which the damage of retinal ganglion cells occurs.

PMID- 26201359
TI  - [Stereotactic Rediosurgery for Uveal Melanoma; Postradiation Complications].
AB  - OBJECTIVE: The authors evaluate a group of patients with malignant uveal melanoma
      treated with stereotactic radiosurgery in the year. 2009-2011 on a linear
      accelerator LINAC. MATERIAL AND METHODS: In 2009-2011 were followed 40 patients
      with malignant melanoma of the uvea in stage T2 and T3 treated with stereotactic
      radiosurgery (LINAC), the therapeutic dose of 35,0 Gy TD, TD max 42,0 Gy. We
      evaluated the influence of factors (age, exposure risk structures, time) to
      intraocular pressure (IOP) and temporal changes in intraocular pressure after
      surgery between the control group and the group of patients who underwent
      enucleation. The normality of data distribution was tested Shapiro-Wilk W test
      and graphically. The relations between the parameters were tested using simple
      and multiple linear regression (correlation coefficient r, the significance level
      p). RESULTS: The mean age of the group of 40 patients with malignant melanoma of
      the uvea treated by one day session stereotactic radiosurgery on a linear
      accelerator in the year. 2009-2011 was 55.13+/-11.11 years. Average maximum
      radiation dose to sensitive structures has been the target of 12,0 Gy to the
      optic nerve and the ciliary 10,0 Gy. The analysis in our group confirmed that the
      prevalence of the tumor independent of sex, increasing with age, with most
      patients are diagnosed between 60 and 70 years of age. Analysis of the difference
      in intraocular pressure (IOP) before surgery showed no significant difference
      between the group of men and women (p=0.54). Using simple linear regression, we
      confirmed assumptions, related to IOP before stereotactic radiosurgery with age
      (r=-0.09, p=0.65). Multiple linear regression, we evaluated the relationship
      between predictors (dose at-risk structures--lens and optic nerve) and the change
      in IOP from the value before stereotactic radiosurgery at each time interval.
      Relations between predictors (Dose aperture--L, the dose of the optic nerve--O)
      and IOP of the file being described partial correlation coefficients after 2
      weeks. For the relationship is significant correlation between the dose and the
      IOP in the lens at the time of 1 year, 1.5 years, and 2 years after the
      stereotactic radiosurgery. CONCLUSION: A single stereotactic radiosurgery on a
      linear accelerator LINAC is possible at a dose of 35,0 to 38,0 Gy in intraocular
      melanomas in stage T1 to T3. According to our results, this is a highly effective
      method of treatment of uveal melanomas elevation to 6 mm and a capacity of up to
      0,4 cm3. Secondary glaucoma is one of the most serious causes of enucleation
      after one day session stereotactic radiosurgery at linear accelerator (LINAC) for
      uveal melanoma. The percentage of enucleation in our investigated group (17.5%)
      for secondary glaucoma is about the same as in other studies.

PMID- 26201360
TI  - [Intrinsically Photosensitive Retinal Ganglion Cells].
AB  - Recently discovered intrinsically photosensitive melanopsin-containing retinal
      ganglion cells contribute to circadian photoentrainment and pupillary
      constriction; recent works have also brought new evidence for their accessory
      role in the visual system in humans. Pupil light reaction driven by individual
      photoreceptors can be isolated by means of the so called chromatic pupillography.
      The use of chromatic stimuli to elicit different pupillary responses may become
      an objective clinical pupil test in the detection of retinal diseases and in
      assessing new therapeutic approaches particularly in hereditary retinal
      degenerations like retinitis pigmentosa. In advanced stages of disease, the pupil
      light reaction is even more sensitive than standard electroretinography for
      detecting residual levels of photoreceptor activity. This review summarizes
      current knowledge on intrinsically photosensitive retinal cells and highlights
      its possible implications for clinical practice.

PMID- 26201361
TI  - [Malignant Choroidal Melanoma in T4 Orbital Stage; Prosthesis of the Orbit].
AB  - AIM: Diagnosis and treatment of tumors of the eye is extremely difficul; surgical
      treatment in advanced stages, when the tumor grows in the orbit, leads to
      extensive radical surgery of the face. The extent and nature of surgical
      procedures depends on the nature of the tumor process, in advanced stages is
      indicated mutilating surgery--exenteration of the orbit. Exenteration of the
      orbit due to the extrascleral extension of malignant melanoma of the uvea is very
      rare, unfortunately, even today in certain cases it is necessary to make such a
      mutilating surgery. MATERIALS AND METHODS: Case report--65 year old female
      patient, sent to our Departement in 2008 with the finding of the pigment deposits
      on the posterior pole of the left eye. Ultrasound study found elevations of up to
      3 mm, she was asked to come for further control in three months interval. She did
      not coma, furthermore she sporadically attended another eye clinic. In 2011 she
      was treated for secondary glaucoma--cyclocryopexia. Due to pain another surgery-
      tarzoraphia was indicated. In 2012 she underwent surgery at St. Elisabeth Cancer
      Institute in Bratislava--Nefrectomia transperitoneally l. dx., excision hepatis.
      Histological examination in addition to the primary papillary renal carcinoma-
      mucinous tubular T1 Nx Mx type, found the metastasis of malignant melanoma to the
      liver and right kidney. She underwent the diagnostic procedure to find the origo
      of the melanoma. The patient was subsequently admitted to our clinic with blind
      painfull eye for enucleation. During the surgery the was found retrobulbar tumor
      ingrowth. Histopatholigical findings confirmed malignant melanoma. Indicated was
      exenteration of the orbit due to malignant melanoma T4 N0 M2 stage in June 2012.
      After healing of the cavity she was recommended to design an individual
      prosthesis. After completing several courses of palliative chemotherapy during a
      recent review in January 2015 the patient is without recurrence of the melanoma
      in the orbit RESULTS: Histological examination confirmed malignant melanoma in
      stage G2, predominantly epithelioid type, spindle cell type in part B of pips,
      tumor fills the entire back and part of the anterior chamber, grows through the
      sclera and optic nerve is completely overgrown by tumor mass and spreads into
      orbit. The immunophenotype is suggesting a better prognosis (S100+, melanoma+,
      +HMB45, cyklin D1 3%, 10% of p53, Ki67 3%). Tissue eyelashes were infiltrated by
      numerous micrometastases. The patient after exenteration of the orbit after 3
      months got an individual epithesis. Local orbit cavity is more than 24 months
      after exenteration without recurrence of melanoma. The patient is still
      undergoing outpatient chemotherapy and feels good. CONCLUSION: The treatment of
      malignant tumors of the orbit and the eye is difficult, in most cases surgical
      treatment is indicated, with the additional radiation therapy and chemotherapy.
      Malignant tumors at an advanced stage should to be solved radically. Exenteration
      of the orbit leads to produce a large defect in the orbit and this part of the
      face. Patients in the active age after surgery followed by facial defects after
      such procedures have disadvantage in work and thie defect leads to serious socio
      economic challenges. Patients with individually made prosthesis comprising a
      refund of the eyeball and the surrounding soft tissues allow active life and full
      application of the private as well as professional life.

PMID- 26201362
TI  - [Treatment of Keratoconus with Corneal Cross-linking--Results and Complications
      in 2 Years Follow-up].
AB  - OBJECTIVE: The objective of the study was to assessment of changes of monitored
      parameters after CXL. Incidence of complications were assessed in the whole group
      and in groups of patients divided according to the selected criteria. Evaluated
      parameters were also relations between them and in time. METHODS: The 86 eyes of
      patients with progressive keratoconus who underwent CXL according to the Dresden
      protocol in the years 2007-2009 at the Ophthalmic clinic FN Brno Bohunice were
      included in this study. RESULTS: There was observed significant increase of BCVA
      (letters--before CXL 42,30+/-10,35, 1st year after CXL (1Y) 44,68+/-10,04,
      p<0,01, 2nd year after CXL (2Y) 44,44+/-10,57, p<0,01) and SE (-5,95+/-3,98D, 
      5,27+/-3,84D, p<0,01, -4,94+/-3,68D, p<0,01), and decrease of maximum curvature
      of the cornea (MAX--before CXL 50,39+/-4,17D, 1Y 49,46+/-4,13D, p<0,01, 2Y
      49,42+/-4,14D, p<0,01). Change of ultrasound CCT, polymegatisms, pleomorfisms and
      corneal endothelial cell density was not significant. The value of MAX is the
      most important parameter in estimating the effect of CXL. The highest incidence
      of corneal opacity after CXL was observed in the eyes of patients with III. stage
      of keratoconus over 40 years old, carrying hard contact lenses and with
      biomikroskopic symptom of keratoconus on the cornea. We found that corneal
      thickness measurement with Orbscan II and the mesurement of IOP with noncontact
      method is incorrect by patients after CXL. CONCLUSION: Corneal cross-linking of
      the cornea is safe and effective procedure of stopping the progression of
      keratoconus in 97% of eyes in the period up to 2 years after CXL.

PMID- 26201363
TI  - [Surgical Treatment of the Idiopathic Macular Hole by Means of 25-Gauge Pars
      Plana Vitrectomy with the Peeling of the Internal Limiting Membrane Assisted by
      Brilliant Blue and Gas Tamponade].
AB  - 25-gauge pars plana vitrectomy with briliant blue assisted internal limiting
      membrane peeling and gas tamponade for idiopatic macular hole. PURPOSE: The
      evaluation of anatomic and visual outcomes in idiopatic macular holes treated
      with 25-gauge pars plana vitrectomy, briliant blue (BB) assisted internal
      limiting membrane (ILM) peeling and gas tamponade. MATERIALS AND METHODS:
      Retrospective analysis. 53 eyes of 52 patients (39 women, 13 men) of mean age
      68,8 years (58-83) with the diagnosis of stage 2, 3, or 4 macular holes according
      to Gass Classification from 6/2012 to 7/2014 were included. All patient undergone
      25-gauge pars plana vitrectomy with brillinat blue assisted ILM peeling, gas
      tamponade (35 cases 15 % C3F8, 18 cases 20% SF6). 50 cases (94,3%) were performed
      in retrobulbar anesthesia, 3 cases in general anesthesia. Face-down positioning
      should have beeen maintained for three days. Best corrected visual acuity (BCVA),
      optical coherence tomography findings and complications were evaluated. RESULTS:
      The mean follow-up time was 6 months (1-22). Macular hole closure was achieved in
      49 eyes (92,5%). The mean BCVA improved from 0,16 (0,5-0,05) to 0,5 (1,0-0,1).
      BCVA was improved by 3 and more ETDRS lines in 42 eyes (79,2%). CONCLUSION: 25
      gauge pars plana vitrectomy with briliant blue assisted internal limiting
      membrane peeling and gas tamponade is safe and effective method of macular hole
      therapy with high anatomic and functional effect.

PMID- 26201364
TI  - [Multifocal Vitelliform Retinal Lesion].
AB  - The authors present retrospective follow up of patient with bilateral multifocal
      vitelliform retinal lesion during the 18 years period. At this time, spontaneous
      improvement of objective picture on retina and subjective visual troubles was
      observed. It is probable, that this case is a part of the same symptom complex as
      a variant of Best's hereditary disease. This conclusion was based on initial
      stadium of phenotypical expressivity and additional evaluations. The course and
      outcomes of visual functions were different. The hereditary transmission was not
      confirmed.

PMID- 26201365
TI  - Investigation of metamemory functioning in the at-risk mental state for
      psychosis.
AB  - BACKGROUND: Metamemory describes the monitoring and knowledge about one's memory
      capabilities. Patients with schizophrenia have been found to be less able in
      differentiating between correct and false answers (smaller confidence gap) when
      asked to provide retrospective confidence ratings in previous studies.
      Furthermore, higher proportions of very-high-confident but false responses have
      been found in this patient group (high knowledge corruption). Whether and how
      these biases contribute to the early pathogenesis of psychosis is yet unclear.
      This study thus aimed at investigating metamemory function in the early course of
      psychosis. METHOD: Patients in an at-risk mental state for psychosis (ARMS, n =
      34), patients with a first episode of psychosis (FEP, n = 21) and healthy
      controls (HCs, n = 38) were compared on a verbal recognition task combined with
      retrospective confidence-level ratings. RESULTS: FEP patients showed the smallest
      confidence gap, followed by ARMS patients, followed by HCs. All groups differed
      significantly from each other. Regarding knowledge corruption, FEP patients
      differed significantly from HCs, whereas a statistical trend was revealed in
      comparison of ARMS and FEP groups. Correlations were revealed between metamemory,
      measures of positive symptoms and working memory performance. CONCLUSIONS: These
      data underline the presence of a metamemory bias in ARMS patients which is even
      more pronounced in FEP patients. The bias might represent an early cognitive
      marker of the beginning psychotic state. Longitudinal studies are needed to
      unravel whether metacognitive deficits predict the transition to psychosis and to
      evaluate therapeutic interventions.

PMID- 26201366
TI  - Isolation and antitumor efficacy evaluation of a polysaccharide from Nostoc
      commune Vauch.
AB  - Nostoc commune Vauch. has been traditionally used as a healthy food and medicine
      for centuries especially in China. It has been demonstrated that the
      polysaccharides isolated from Nostoc commune Vauch. exhibit strong antimicrobial
      and antioxidant activities. However, little is known about their anticancer
      activities and the underlying mechanisms of action. Herein, we report the
      isolation of a polysaccharide from Nostoc commune Vauch. (NVPS), and its
      physicochemical properties were analyzed. In an attempt to demonstrate the
      potential application of NVPS in tumor chemotherapy, the in vitro antitumor
      activity was determined. NVPS significantly suppressed the growth and
      proliferation of MCF-7 and DLD1 cells. The molecular mechanism underlying this in
      vitro antitumor efficacy was elucidated, and the results indicated that NVPS
      simultaneously triggered intrinsic, extrinsic and endoplasmic reticulum stress
      (ERS)-mediated apoptotic signaling pathways. Collectively, these findings
      demonstrate that NVPS could be used as a novel promising source of natural
      antitumor agents. 

PMID- 26201367
TI  - Guided access cavity preparation using cone-beam computed tomography and optical
      surface scans - an ex vivo study.
AB  - AIM: To evaluate ex vivo, the accuracy of a preparation procedure planned for
      teeth with pulp canal obliteration (PCO) using a guide rail concept based on a
      cone-beam computed tomography (CBCT) scan merged with an optical surface scan.
      METHODOLOGY: A total of 48 teeth were mounted in acrylic blocks. An apical canal
      preparation was created to simulate remnants of an apical root canal that acted
      as the target for a drill path. The test blocks were surface scanned, and merged
      with a CBCT scan, and a guide rail was made. A pathway for the bur was created
      through a metal sleeve within the guide rail into dentine. The distance was
      measured between the centres of the performed drill path and the apical target by
      two examiners. A maximum distance of 0.7 mm was defined based on the radius of
      the bur (0.6 mm) and the radius of a root canal just visible on a radiograph (0.1
      mm). The t-test was used for evaluation, and intra- and inter-examiner
      reproducibility was expressed by intraclass correlation coefficients. RESULTS:
      The mean distance between the drill path and the target was significantly lower
      than 0.7 mm, and null hypothesis H0 : MU = 0.7 was rejected (CI 95%: 0.31;0.49, P
      < 0.001). Intra- and inter-examiner agreements reached excellent levels.
      CONCLUSIONS: The combined use of CBCT and optical scans for the precise
      construction of a guide rail led to a drill path with a precision below a risk
      threshold. The present technique may be a valuable tool for the negotiation of
      partial or complete pulp canal obliteration.

PMID- 26201368
TI  - Hybrid Versus Conventional Treatment of Acute Type A Aortic Dissection.
AB  - BACKGROUND: To determine whether the hybrid approach to acute type A aortic
      dissection results in improved outcomes in terms of mortality, neurologic
      complications, need for distal aortic reintervention, and false lumen thrombosis
      compared with the conventional approach. METHODS: Data from comparative studies
      of hybrid versus conventional treatment of acute type A aortic dissection were
      combined through meta-analysis. Pooled odd ratios were calculated using random
      effects models. RESULTS: Seven comparative studies including 967 patients were
      identified; of these, 503 underwent conventional proximal aortic repair and 429
      extensive distal aortic repair including a stented elephant trunk technique.
      Between the two groups there was no significant difference in operative mortality
      (p = 0.96), permanent neurologic deficit (p = 0.95), and late mortality (p =
      0.59). Distal aortic repair showed a higher rate of false lumen thrombosis of the
      thoracic aorta (odd ratio 11.16; p < 0.001) and a reduced risk of distal
      reintervention (odd ratio 0.37; p = 0.01). In sub-group analysis, frozen elephant
      trunk procedure showed a lower rate of distal aortic reintervention and a higher
      rate of false lumen thrombosis than antegrade/retrograde stent deployment
      techniques (p = 0.008 and <0.001, respectively). CONCLUSIONS: Distal aortic
      repair may reduce the risk of distal reintervention and increase the rate of
      false lumen thrombosis without significant increase in operative mortality and
      permanent neurologic deficit; however, no benefit with respect to late mortality
      was found. The frozen elephant trunk may reduce the risk of distal aortic
      reintervention and may increase the false lumen thrombosis of the thoracic aorta
      in comparison with antegrade/retrograde stent deployment procedures.

PMID- 26201369
TI  - Diesel exhaust particles exacerbate allergic rhinitis in mice by disrupting the
      nasal epithelial barrier.
AB  - BACKGROUND: Diesel exhaust particles (DEP), traffic-related air pollutants, are
      considered environmental factors that affect allergic diseases adversely.
      However, the exact effect of DEP on allergic rhinitis (AR) is unclear. OBJECTIVE:
      We thought to investigate the effect of DEP on seasonal AR using a mouse model.
      METHODS: Ragweed-pollen-sensitized mice were nasally challenged with ragweed
      pollen in the presence or absence of DEP. The frequency of sneezing was evaluated
      immediately after each nasal challenge. The expression of a tight junction (TJ)
      protein, zonula occludens-1 (ZO-1), was examined by immunohistochemistry in AR
      mice. RPMI 2650 cells were used for in vitro examination of paracellular
      permeability. RESULTS: Mice challenged with ragweed pollen plus DEP showed
      increased frequency of sneezing compared with mice challenged with pollen alone.
      Interestingly, intranasal DEP pretreatment before ragweed pollen challenge
      increased ragweed-pollen-induced sneezing to levels comparable with the co
      administration group. In vitro examination revealed that DEP reduced ZO-1
      expression in RPMI 2650 cells. In addition, intranasal administration of DEP, but
      not ragweed pollen, disrupted nasal mucosal TJs in vivo. The effect of a single
      DEP treatment on ragweed-induced sneezing and ZO-1 expression persisted for at
      least 4 days and was inversely correlated. Finally, an antioxidant substance, N
      acetyl-L-cysteine, inhibited DEP-mediated TJ disruption and exacerbation of
      sneezing in AR. CONCLUSIONS AND CLINICAL RELEVANCE: DEP disrupts TJs by a
      reactive oxygen species-mediated pathway, leading to the increased permeability
      of nasal epithelial cells. This may result in the promotion of allergen delivery
      into subepithelial tissues contributing to the exacerbation of immediate allergic
      responses.

PMID- 26201370
TI  - Yolk-sac larval development of the substrate-brooding cichlid Archocentrus
      nigrofasciatus in relation to temperature.
AB  - In order to conserve and culture the cichlid fish Archocentrus nigrofasciatus,
      more information about its reproductive biology and its larval behavior and
      morphogenesis is necessary. Currently, temperatures ranging from 21 to 27 
      degrees C are used in ornamental aquaculture hatcheries. Lower temperatures are
      preferred to reduce the costs of water heating, and 23  degrees C is usually the
      selected temperature. However, there is limited information on culturing
      protocols for ornamental species and most of the information generated on this
      topic remains scarce. Thus, the present study examines the morphological
      development of Archocentrus nigrofasciatus during the yolk-sac period up to the
      age of 100 h post-hatching in relation to 2 temperature regimes used in
      ornamental aquaculture: a temperature of 27  degrees C (thermal optimum) and a
      decreased temperature of 23  degrees C (thermal tolerance). The results of this
      study suggest that the 27  degrees C temperature generates intense morphological
      changes in yolk-sac development in a shorter period. This has advantages as it
      reduces the time of yolk-sac larval development, and, thus, minimizes the
      transition phase to exogenous feeding and maximizes the efficiency at which yolk
      is converted into body tissues. The present paper provides necessary information
      to produce freshwater ornamental fish with better practices so as to increase
      larval survival and capitalize on time for growth. 

PMID- 26201371
TI  - The Microscopic Structure of the Omentum in Healthy Dogs: The Mystery Unravelled.
AB  - The canine omentum has many valuable properties but is still an underestimated
      organ. It contributes in many ways to the protection of the peritoneal cavity
      through its versatility on immunological level, but also through its role during
      angiogenesis, absorption, adhesion and fat storage. Despite a wide range of
      applications, the basic structure of the omentum is not well documented. This
      study provides an insight in the microscopic structure of the canine omentum
      through both light microscopic and electron microscopic investigations. Two
      regions could be distinguished in the canine omentum: translucent and adipose
      rich regions. The translucent regions were composed of two different layers: a
      continuous flattened mesothelium on top of a submesothelial connective tissue
      matrix. The adipose-rich regions consisted of a substantial layer of adipocytes
      on which a flattened continuous mesothelium was present. Between those two
      layers, a few strands of collagen fibres could be detected. Large aggregates of
      immune cells, the so-called milky spots, were not observed in the omentum of
      healthy dogs. Only a limited number of leucocytes, macrophages and neutrophils
      were found, scattered throughout the connective tissue in the translucent
      regions. At the level of the adipose-rich regions, the immunological population
      was virtually non-existent. 

PMID- 26201372
TI  - Malignant melanoma disguised in a tattoo.

PMID- 26201373
TI  - Mortality and length of stay in elderly toxic epidermal necrolysis patients.

PMID- 26201374
TI  - Iododerma in pregnancy secondary to iodinated multivitamins.

PMID- 26201375
TI  - Allergic contact dermatitis to topical brimonidine.

PMID- 26201376
TI  - Subsequent skin cancer in patients with early-onset basal cell carcinoma.

PMID- 26201378
TI  - Adalimumab-induced porokeratosis.

PMID- 26201379
TI  - Dermoscopy of pigmented fungiform papillae of the tongue in an Indian girl.

PMID- 26201380
TI  - Metabolomics analysis of saliva from patients with primary Sjogren's syndrome.
AB  - The recent development of salivary proteomics has led to the identification of
      potential biomarkers for diagnosing patients with primary Sjogren's syndrome
      (pSS). Here we sought to identify differentially produced salivary metabolites
      from pSS patients and healthy controls (HCs) that might be used to characterize
      this disease. We obtained salivary samples from 12 female pSS patients (mean age
      44.2 +/- 13.01) and 21 age-matched female HCs. The metabolite profiles of saliva
      were analysed by gas chromatography-mass spectrometry. The total metabolite
      levels in each of the samples were calculated and compared across the study
      participants. A total of 88 metabolites were detected across the study samples,
      41 of which were observed at reduced levels in the samples from pSS patients.
      Principal component analysis (PCA) revealed a loss in salivary metabolite
      diversity in the pSS patient samples compared to the HC samples. The reduced
      presence of glycine, tyrosine, uric acid and fucose, which may reflect salivary
      gland destruction due to chronic sialoadenitis, contributed to the loss of
      diversity. Comparative PCA of the pSS patients revealed the presence of two
      subpopulations based on their metabolite profiles, and these two subpopulations
      showed a significant difference in the prevalence of major salivary glanditis (P
      = 0.014). In this study, we found that the salivary metabolite profile of pSS
      patients was less diverse than that of HCs and that the metabolite profiles in
      pSS patients were affected by the presence of major salivary glanditis.

PMID- 26201381
TI  - Effects of pathogen exposure on life-history variation in the gypsy moth
      (Lymantria dispar).
AB  - Investment in host defences against pathogens may lead to trade-offs with host
      fecundity. When such trade-offs arise from genetic correlations, rates of
      phenotypic change by natural selection may be affected. However, genetic
      correlations between host survival and fecundity are rarely quantified. To
      understand trade-offs between immune responses to baculovirus exposure and
      fecundity in the gypsy moth (Lymantria dispar), we estimated genetic correlations
      between survival probability and traits related to fecundity, such as pupal
      weight. In addition, we tested whether different virus isolates have different
      effects on male and female pupal weight. To estimate genetic correlations, we
      exposed individuals of known relatedness to a single baculovirus isolate. To then
      evaluate the effect of virus isolate on pupal weight, we exposed a single gypsy
      moth strain to 16 baculovirus isolates. We found a negative genetic correlation
      between survival and pupal weight. In addition, virus exposure caused late
      pupating females to be identical in weight to males, whereas unexposed females
      were 2-3 times as large as unexposed males. Finally, we found that female pupal
      weight is a quadratic function of host mortality across virus isolates, which is
      likely due to trade-offs and compensatory growth processes acting at high and low
      mortality levels, respectively. Overall, our results suggest that fecundity costs
      may strongly affect the response to selection for disease resistance. In nature,
      baculoviruses contribute to the regulation of gypsy moth outbreaks, as pathogens
      often do in forest-defoliating insects. We therefore argue that trade-offs
      between host life-history traits may help explain outbreak dynamics. 

PMID- 26201382
TI  - Melatonin and endoplasmic reticulum stress: relation to autophagy and apoptosis.
AB  - Endoplasmic reticulum (ER) is a dynamic organelle that participates in a number
      of cellular functions by controlling lipid metabolism, calcium stores, and
      proteostasis. Under stressful situations, the ER environment is compromised, and
      protein maturation is impaired; this causes misfolded proteins to accumulate and
      a characteristic stress response named unfolded protein response (UPR). UPR
      protects cells from stress and contributes to cellular homeostasis re
      establishment; however, during prolonged ER stress, UPR activation promotes cell
      death. ER stressors can modulate autophagy which in turn, depending of the
      situation, induces cell survival or death. Interactions of different autophagy-
      and apoptosis-related proteins and also common signaling pathways have been
      found, suggesting an interplay between these cellular processes, although their
      dynamic features are still unknown. A number of pathologies including metabolic,
      neurodegenerative and cardiovascular diseases, cancer, inflammation, and viral
      infections are associated with ER stress, leading to a growing interest in
      targeting components of the UPR as a therapeutic strategy. Melatonin has a
      variety of antioxidant, anti-inflammatory, and antitumor effects. As such, it
      modulates apoptosis and autophagy in cancer cells, neurodegeneration and the
      development of liver diseases as well as other pathologies. Here, we review the
      effects of melatonin on the main ER stress mechanisms, focusing on its ability to
      regulate the autophagic and apoptotic processes. As the number of studies that
      have analyzed ER stress modulation by this indole remains limited, further
      research is necessary for a better understanding of the crosstalk between ER
      stress, autophagy, and apoptosis and to clearly delineate the mechanisms by which
      melatonin modulates these responses. 

PMID- 26201383
TI  - Sex Difference in Coronary Endothelial Dysfunction in Apolipoprotein E Knockout
      Mouse: Role of NO and A2A Adenosine Receptor.
AB  - OBJECTIVE: Sex plays an important role in the pathophysiology of cardiovascular
      diseases. This study aims to investigate how sex impacts on the coronary flow
      regulation during atherosclerosis. METHODS: ApoE KO mouse fed with western diet
      were used for atherosclerosis model. Coronary RH and flow response were measured
      using Langendorff-perfused isolated hearts. RESULTS: Coronary RH and A23187
      induced NO-dependent flow increases were significantly reduced in female (by ~28%
      and 48%, respectively), but not in male atherosclerotic mice. However, SNP
      induced coronary vasodilation remains intact in both sexes of ApoE KO mice. L
      NAME (NOS inhibitor) reduced baseline flow and RH to a lesser extent in ApoE KO
      (by ~19% and 31%) vs. WT (~30% and 59%, respectively), and abolished the sex
      difference in RH. In contrast, SCH58261 (a selective A2A AR antagonist) reduced
      the baseline flow and RH to a greater extent in atherosclerotic mice, but did not
      affect the sex difference. Immunofluorescent staining of coronary arteries showed
      a similar A2A AR upregulation in both sexes of ApoE KO mice. CONCLUSIONS: Our
      results suggest that during atherosclerosis, female mice are more susceptible to
      NO-dependent endothelial dysfunction and the upregulation of A2A AR may serve as
      a compensatory mechanism to counteract the compromised endothelial function.

PMID- 26201384
TI  - The role of fungal sensitisation in clinical presentation in patients with
      chronic obstructive pulmonary disease.
AB  - Atopic patients with chronic obstructive pulmonary disease (COPD) demonstrate
      more severe symptoms than their non-atopic counterparts. Also, Aspergillus
      hypersensitivity is known in COPD. However, allergic sensitisation to non
      Aspergillus fungi has never been studied in COPD patients. To evaluate the
      prevalence of fungal sensitisation and its impact on the clinical presentation
      and outcome of COPD patients. Sensitisation to 17 fungi was studied in 55 COPD
      patients through skin prick tests, fungus-specific IgE, precipitating antibodies,
      total IgE and eosinophil counts. The clinical symptoms of patients were monitored
      thorough a patient-administered questionnaire. Overall, 5.4% (n = 3) of COPD
      patients were fungus sensitive. The sensitisation was noted to Alternaria
      alternata and Schizophyllum commune in two patients each, whereas another was
      sensitive to A. tamarii, Rhizopus spp. and Aspergillus fumigatus. Eosinophils
      were higher in fungus-sensitised patients (P = 0.001 vs. 0.003). No differences
      were noted in the clinical presentation of patients sensitised to fungi compared
      to those not sensitised to fungi or non-atopic. Although low, fungal
      sensitisation occurs in COPD but it is not limited to Aspergilli alone. Fungus
      sensitised patients exhibit greater eosinophilia, implying more severe
      inflammation. Thus, such patients should be followed up regularly to recognise
      clinical worsening or development of ABPM.

PMID- 26201385
TI  - Racial/Ethnic Differences in Gestational Diabetes Prevalence and Contribution of
      Common Risk Factors.
AB  - BACKGROUND: The White House, the American Heart Association, the Agency for
      Healthcare Research and Quality, and the National Heart, Lung and Blood Institute
      have all recently acknowledged the need to disaggregate Asian American subgroups
      to better understand this heterogeneous racial group. This study aims to assess
      racial/ethnic differences in relative contribution of risk factors of gestational
      diabetes mellitus (GDM) among Asian subgroups (Asian Indian, Chinese, Filipino,
      Japanese, Korean, and Vietnamese), Hispanics, non-Hispanic blacks, and non
      Hispanic whites. METHODS: Pregnant women in 2007-2012 were identified through
      California state birth certificate records and linked to the electronic health
      records in a large mixed-payer ambulatory care organisation in Northern
      California (n = 24 195). Relative risk and population attributable fraction (PAF)
      for specific racial/ethnic groups were calculated to assess the contributions of
      advanced maternal age, overweight/obesity (Centers for Disease Control and
      Prevention (CDC) standards and World Health Organization (WHO)/American Diabetes
      Association (ADA) body mass index cut-offs for Asians), family history of type 2
      diabetes, and foreign-born status. RESULTS: GDM was most prevalent among Asian
      Indians (19.3%). Relative risks were similar across all race/ethnic groups.
      Advanced maternal age had higher PAFs in non-Hispanic whites (22.5%) and
      Hispanics (22.7%). Meanwhile family history (Asian Indians 22.6%, Chinese 22.9%)
      and foreign-borne status (Chinese 40.2%, Filipinos 30.2%) had higher PAFs in
      Asian subgroups. Overweight/obesity was the most important GDM risk factor for
      non-Hispanic whites, Hispanics, Asian Indians, and Filipinos when the WHO/ADA cut
      off points were applied. Advanced maternal age was the only risk factor studied
      that was modified by race/ethnicity, with non-Hispanic white and Hispanic women
      being more adversely affected than other racial/ethnic groups. CONCLUSIONS:
      Overweight/obesity, advanced maternal age, family history of type 2 diabetes, and
      foreign-borne status are important risk factors for GDM. The relative
      contributions of these risk factors differ by race/ethnicity, mainly due to
      differences in population prevalence of these risk factors.

PMID- 26201386
TI  - What is the intrapatient variability of mycophenolic acid trough levels?
AB  - TDM of MPA, the active compound of MMF, is rarely used despite its substantial
      intra- and interpatient variability. Little is known about the utility of long
      term MPA TDM. Data are expressed as mean (one standard deviation). All available
      data from 27 renal transplant recipients (mean age at transplantation: 7.7 [5.0]
      yr) with an average follow-up of 9.3 (4.6) yr were analyzed. MPA levels were
      measured using the EMIT. GFR was measured using cystatin C and eGFR was
      calculated using the Filler formula. Intrapatient CV of the trough level was
      calculated as the ratio of the mean divided by one standard deviation. Mean
      cystatin C eGFR was 56.9 (24.4) mL/min/1.73 m(2) . There was a weak but
      significant correlation between the MPA trough level and the AUC (Spearman r =
      0.6592, p < 0.0001). A total of 1964 MPA trough levels (73 [45]/patient) were
      measured, as compared to 3462 Tac trough levels (144 [71]/patient). The average
      MPA trough level was 3.01 (1.26) mg/L and the average trough Tac level was 7.3
      (1.8) ng/mL. Intrapatient CV was statistically higher (p = 0.00093) for MPA at
      0.68 (0.29) when compared to Tac with a CV of 0.46 (0.12). CV did not correlate
      with eGFR. Intrapatient MPA trough level CV is significantly higher than for Tac,
      while CV for both MPA and Tac was high. MPA trough level monitoring may be a
      feasible monitoring option to improve patient exposure and possibly outcomes.

PMID- 26201387
TI  - The cost-effectiveness of quality improvement projects: a conceptual framework,
      checklist and online tool for considering the costs and consequences of
      implementation-based quality improvement.
AB  - In resource constrained systems, decision makers should be concerned with the
      efficiency of implementing improvement techniques and technologies. Accordingly,
      they should consider both the costs and effectiveness of implementation as well
      as the cost-effectiveness of the innovation to be implemented. An approach to
      doing this effectively is encapsulated in the 'policy cost-effectiveness'
      approach. This paper outlines some of the theoretical and practical challenges to
      assessing policy cost-effectiveness (the cost-effectiveness of implementation
      projects). A checklist and associated (freely available) online application are
      also presented to help services develop more cost-effective implementation
      strategies.

PMID- 26201388
TI  - Prevalence of Spinal Cord Injury in Iran: A 3-Source Capture-Recapture Study.
AB  - BACKGROUND: Epidemiologic data of spinal cord injured (SCI) patients are
      necessary for prevention policymaking and improvement of social and healthcare
      support to patients. This study was designed to estimate the prevalence of
      traumatic and non-traumatic SCI in Iran in a three-source capture-recapture
      study. METHODS: Three organizations, which provide supports to SCI patients were
      identified. Demographic data of patients in each organization was obtained.
      Datasets were formed and matching data were found. Matched data were incorporated
      into STATA 12 for log linear analyses. Results of sensitivity analyses were used
      to estimate total number of SCI patients in Iran. Veterans of Iraq-Iran conflict
      were added as separate data source to final results. RESULTS: The prevalence of
      traumatic and non-traumatic SCI patients is 296.87 (95% confidence intervals
      (CI): 292.04-302.48) per million in Tehran and Alborz provinces. The prevalence
      of SCI in Iran is an estimated 318.45 (95% CI: 312.98-324.54) per million.
      CONCLUSION: The prevalence of SCI in Iran is among the lowest figures reported in
      the literature. The supporting organizations in Iran do not have details about
      the cause, level and severity of SCI patients. A national study to register SCI
      patients' data is needed.

PMID- 26201389
TI  - Delineating the Mosaic Trisomy 15 Phenotype Using a Serendipitous Mechanism as a
      Clue.
AB  - Parental balanced translocation is one of the traditional indications for
      invasive prenatal diagnosis. Usually, the diagnostic process is straightforward.
      Sometimes, however, results are not entirely clear and may reveal unexpected
      biological processes. We performed chorionic villi sampling for a paternal 8;15
      reciprocal translocation in the sixth pregnancy of a Caucasian woman. Cytogenetic
      analysis of chorionic villi, after both short- and long-term cultures, revealed
      the presence of the same rearrangement found in the father as well as a trisomy
      15. Surprisingly, the trisomy, which was initially expected to derive from
      aberrant segregation during paternal meiosis, resulted instead from maternal
      nondisjunction. Although a sonogram of the fetus appeared to be normal, follow-up
      amniocentesis demonstrated a low-level mosaic trisomy 15 in cells extracted from
      the amniotic fluid, while 10% of cells from fetal tissues sampled after
      termination of the pregnancy were also found to be trisomic. Fetal autopsy showed
      dysmorphic features, confirming the diagnosis of mosaic trisomy 15 and enabled
      deeper insight into the prenatal phenotype of this rare condition. 

PMID- 26201390
TI  - Risk factors for sepsis in Korean trauma patients.
AB  - PURPOSE: Sepsis in severely injured patients is one of the leading causes of
      death in hospitals. The incidence of and risk factors for sepsis after trauma
      have been studied outside, but not within Korea. Therefore, this study
      investigated the incidence of sepsis and the independent risk factors for sepsis
      in moderately to severely injured patients in Korea. METHODS: The electronic
      medical records of patients who visited the emergency department from January
      2010 to December 2012 were reviewed retrospectively. Patients older than 18 years
      of age with an Injury Severity Score (ISS) greater than or equal to nine points
      were included. RESULTS: A total of 183 patients met the study inclusion criteria.
      The median ISS was 14 (range 9-17) points and 15 (8 %) patients developed sepsis.
      The patients' age [adjusted OR, 1.053; 95 % confidence intervals (CI), 1.015
      1.094], ISS (adjusted OR, 1.114; 95 % CI, 1.046-1.187), and emergency surgery
      (adjusted OR, 3.727; 95 % CI, 1.051-13.221) were independent risk factors for
      post-traumatic sepsis. CONCLUSIONS: Among the risk factors identified in the
      literature, our research confirmed only the patients' age and ISS as risk factors
      for sepsis after trauma, and, additionally, identified emergency surgery as a
      risk factor in Korean patients. Therefore, trauma patients who have any of the
      risk factors mentioned above have a high risk of post-traumatic sepsis, which
      requires certain precautionary clinical measures.

PMID- 26201391
TI  - Are retrievable vena cava filters placed in trauma patients really retrievable?
AB  - PURPOSE: Concerns have arisen regarding the use of retrievable inferior vena cava
      filters (rIVCFs) in trauma patients due to increasing reports of low retrieval
      rates. We hypothesized that complete follow-up with a dedicated trauma nurse
      practitioner would be associated with a higher rate of retrievability. This study
      was undertaken to determine the rate of retrievability of rIVCFs placed in a
      Canadian Lead Trauma Centre, and to compare the rate of retrievability in our
      trauma population to our non-trauma patients. METHODS: We performed a
      retrospective cohort study of all patients with rIVCF placed between Jan 1 2000
      and June 30 2014. Data were collected on demographics, indication for filter
      placement, retrieval status, and reasons for non-retrieval. Comparison was made
      between trauma patients and non-trauma patients. RESULTS: A total of 374 rIVCFs
      were placed (61 in trauma patients and 313 in non-trauma patients) and follow-up
      was complete for the entire cohort. Filter retrieval was achieved in 86.9 % of
      trauma patients. Reasons for non-retrieval were technical in two patients, and
      death before retrieval in six patients. Retrieval was successful in 48.9 % of non
      trauma patients. CONCLUSIONS: This study demonstrates that rIVCFs can be
      successfully retrieved amongst trauma patients. We demonstrated a higher rate of
      successful retrieval amongst trauma patients than non-trauma patients in our
      institution. Careful patient follow-up may play a role in successful retrieval of
      rIVCFs.

PMID- 26201392
TI  - A case of bronchiolitis obliterans organizing pneumonia in an HIV-infected Korean
      patient successfully treated with clarithromycin.
AB  - BACKGROUND: Bronchiolitis obliterans organizing pneumonia (BOOP) is a type of
      diffuse interstitial lung disease characterized by the pathology of fibroblastic
      plugs in the lumens of the respiratory bronchioles, alveolar ducts, and alveoli.
      The occurrence of BOOP in human immunodeficiency virus (HIV)-infected patients
      has rarely been described, and there have been no clinical case reports in Korea.
      CASE PRESENTATION: A 24-year-old female who had been diagnosed with HIV ten years
      prior was admitted due to a 1-year history of cough and sputum production and a 3
      day history of fever. She had poor adherence to anti-retroviral therapy (ART) due
      to gastrointestinal troubles. At the time of admission, her CD4 T-cell count was
      5 cells/mm(3). A high resolution computed tomography (CT) scan showed tiny
      centrilobular nodules with a tree-in-bud pattern in both lungs. Bacterial
      culture, Pneumocystis jirovecii polymerase chain reaction (PCR), Aspergillus
      galactomannan antigen (Ag) assay, and respiratory virus PCR were negative. Rapid
      chest x-ray improvement was seen after a 7-day treatment with anti-tuberculosis
      medication, ceftriaxone, and clarithromycin. Miliary tuberculosis seemed unlikely
      considering the rapid radiologic improvement and negative tuberculosis PCR
      results. Due to the unknown etiology, we performed video-assisted thoracoscopic
      surgery (VATS) to determine the cause of the diffuse lung infiltration.
      Pathologic findings were consistent with BOOP, while tissue acid-fast bacilli
      (AFB) stain and tuberculosis PCR results were negative. Tuberculosis medication
      and intravenous ceftriaxone were discontinued, while treatment with
      clarithromycin monotherapy was sustained. Five months after discharge, the
      patient was asymptomatic with a normal chest x-ray and as her adherence to ART
      improved, her CD4 T-cell count rose to 181 cells/mm(3). Clarithromycin was
      discontinued at that time and the patient is currently receiving regular
      outpatient follow-up. CONCLUSION: This case suggests that macrolides are a
      potential treatment option in HIV-infected patients with mild BOOP. In cases that
      are otherwise unexplained or unresponsive to treatment, BOOP should be taken into
      consideration and surgical biopsy performed to confirm a diagnosis of BOOP.

PMID- 26201393
TI  - Review by urological pathologists improves the accuracy of Gleason grading by
      general pathologists.
AB  - BACKGROUNDS: Urologists use biopsy Gleason scores for patient counseling,
      prognosis prediction, and decision making. The accuracy of Gleason grading is
      very important. However, the variability of Gleason grading between general
      pathologists cannot be overlooked. Here we evaluate the discrepancy in the
      Gleason grading between 2 urologic pathologists and general pathologists as well
      as improvement in the accuracy of Gleason grading by general pathologists as a
      result of review by urologic pathologists. METHODS: The subjects enrolled in the
      study were 755 patients who underwent prostate needle biopsy at affiliate
      hospitals of Nara Medical University over a period of 2 years. The biopsy samples
      were diagnosed by general pathologists. All biopsy samples were sent to Nara
      Medical University where they were diagnosed by 2 urologic pathologists. The
      results were then returned to the general pathologists. We compared the
      diagnostic accuracy of the general pathologists with that of the urologic
      pathologists for the parameters of no malignancy, atypical small acinar
      proliferation, high grade prostatic intraepithelial neoplasia and Gleason score
      (6, 3 + 4, 4 + 3 and 8-10). We then evaluated the concordance rate between the
      general and urologic pathologists for each of four consecutive 6-month periods.
      RESULTS: The overall concordance rate of urologic pathologists and general
      pathologists in the first, second, third and last 6-month periods was 71.8%
      (140/198), 79.8% (168/225), 89.7% (166/185) and 89.9% (133/148), respectively.
      The concordance rate of the Gleason score between urologic pathologists and
      general pathologists in the first, second, third and last 6-month periods was
      47.5% (38/80), 62.6% (57/91),76.9% (50/65) and 78.7% (48/61), respectively, and
      the kappa value was 0.55, 0.68, 0.81 and 0.84, respectively. The concordance rate
      improved significantly over the course of each period (P = 0.04). CONCLUSION: The
      concordance rate of the Gleason grading between the general pathologists and the
      urologic pathologists was 47.5%. However, improvement of the concordance rate as
      a result of review by the urological pathologist could be seen.

PMID- 26201394
TI  - Risk factors for limb overgrowth after the application of titanium elastic
      nailing in the treatment of pediatric femoral fracture.
AB  - PURPOSE: The objective of this study was to discuss the risk factors of
      postoperative limb overgrowth after the application of titanium elastic nailing
      (TEN) in the treatment of pediatric femoral fractures as well as analyze the
      causes and provide guidance for clinical treatment. METHODS: The study included
      children with femoral fractures who were treated with TEN at our hospital from
      February 2005 to December 2009. Their age, gender, weight, cause of injury,
      having head trauma or not, fracture site, fracture type and nail-canal diameter
      (NCD) ratio were recorded. Student's t-test, chi-square test or Fisher's exact
      test was used for univariate analysis of the above factors, and then multivariate
      logistic regression analysis was used to analyze the possible risk factors in
      order to determine which ones are associated with limb overgrowth after the
      application of TEN to treat children with femoral fractures. RESULTS: Univariate
      analysis showed that the age, gender, weight, cause of injury, having head trauma
      or not, and the fracture site did not have a statistically significant
      association with limb overgrowth (P = 0.741, 0.900, 0.253, 0.739, 0.967 and
      0.105, respectively). The fracture type and NCD ratio were significantly
      associated with limb overgrowth (P = 0.003 and 0.000, respectively). Multivariate
      logistic regression analysis demonstrated that the fracture type (P = 0.021, OR =
      2.757) and NCD ratio (P = 0.002, OR = 2.422) were independent risk factors for
      limb overgrowth. CONCLUSIONS: The main factors affecting postoperative limb
      overgrowth are the fracture type and NCD ratio. In order to avoid limb
      overgrowth, unstable fractures should be fixed as firmly as possible, and the NCD
      ratio should be >=0.8.

PMID- 26201395
TI  - Psychometric properties of the Japanese version of the Tampa Scale for
      Kinesiophobia (TSK-J) in patients with whiplash neck injury pain and/or low back
      pain.
AB  - BACKGROUND: Although the Tampa Scale for Kinesiophobia (TSK) is useful for
      measuring fear of movement in patients with musculoskeletal pain, no
      psychometrically validated Japanese version is available. We evaluated the
      reliability and validity of the Japanese version of the TSK-J (original 17-item
      version and shorter 11-item version). METHODS: The data subset used in this
      psychometric testing was derived from a survey previously conducted to collect
      information on musculoskeletal pain due to motor vehicle accident. For
      reliability, internal consistency was assessed via Cronbach's alpha coefficient.
      For concurrent validity, Pearson correlation coefficients of the TSK-J with the
      pain catastrophizing scale (PCS), euroqol 5 dimension (EQ-5D), and numerical
      rating scales (NRSs) for pain in the neck and back were calculated. For known
      group validity, the relationship between variables (e.g., depression, somatic
      symptoms, treatment period) and the TSK-J score was examined. RESULTS: Data from
      956 persons who had suffered from a motor vehicle accident were used in this
      analysis. For reliability, internal consistency was demonstrated, with Cronbach's
      alpha statistics of 0.850 (TSK-J17) and 0.919 (TSK-J11). For concurrent validity,
      significantly strong correlations were demonstrated between the TSK-J versions
      and PCS total score and subscales (r = 0.602-0.680). For known-group validity, as
      hypothesized, significantly higher TSK-J scores were observed in persons with
      depressive mood, somatic symptoms, and longer treatment period. CONCLUSIONS: The
      present analysis showed that the Japanese versions of the TSK-J17 and TSK-J11
      were psychometrically reliable and valid for detecting fear of movement in the
      Japanese population suffering from neck to back pain due to a motor vehicle
      accident.

PMID- 26201396
TI  - Activity, assay and target data curation and quality in the ChEMBL database.
AB  - The emergence of a number of publicly available bioactivity databases, such as
      ChEMBL, PubChem BioAssay and BindingDB, has raised awareness about the topics of
      data curation, quality and integrity. Here we provide an overview and discussion
      of the current and future approaches to activity, assay and target data curation
      of the ChEMBL database. This curation process involves several manual and
      automated steps and aims to: (1) maximise data accessibility and comparability;
      (2) improve data integrity and flag outliers, ambiguities and potential errors;
      and (3) add further curated annotations and mappings thus increasing the
      usefulness and accuracy of the ChEMBL data for all users and modellers in
      particular. Issues related to activity, assay and target data curation and
      integrity along with their potential impact for users of the data are discussed,
      alongside robust selection and filter strategies in order to avoid or minimise
      these, depending on the desired application. 

PMID- 26201398
TI  - Predicting the characteristics of the aetiological agent for Kawasaki disease
      from other paediatric infectious diseases in Japan.
AB  - Although Kawasaki disease (KD), which was first reported in the 1960s, is assumed
      to be infectious, its aetiological agent(s) remains unknown. We compared the
      geographical distribution of the force of infection and the super-annual
      periodicity of KD and seven other paediatric infectious diseases in Japan. The
      geographical distribution of the force of infection, which was estimated as the
      inverse of the mean patient age, was similar in KD and other paediatric viral
      infections. This similarity was due to the fact that the force of infection was
      determined largely by the total fertility rate. This finding suggests that KD
      shares a transmission route, i.e. sibling-to-sibling infection, with other
      paediatric infections. The super-annual periodicity, which is positively
      associated with the sum of an infectious disease's incubation period and
      infectious period, was much longer for KD and exanthema subitum than other
      paediatric infectious diseases. The virus for exanthema subitum is known to
      persist across the host's lifespan, which suggests that the aetiological agent
      for KD may also be capable of persistent infection. Taken together, these
      findings suggest that the aetiological agent for KD is transmitted through close
      contact and persists asymptomatically in most hosts. 

PMID- 26201399
TI  - Erratum to: Methodological Approaches to Evaluate the Impact of FDA Drug Safety
      Communications.

PMID- 26201397
TI  - Genetic diversity of Ixodes pavlovskyi and I. persulcatus (Acari: Ixodidae) from
      the sympatric zone in the south of Western Siberia and Kazakhstan.
AB  - The most epidemiologically significant tick species in Siberia involved in
      transmission of a large number of pathogens causing human infectious diseases is
      Ixodes persulcatus. Ixodes pavlovskyi, being more active, also poses
      epidemiological threats. These tick species share morphology, activity seasons
      and geographic distribution range. In this paper, we characterize the geographic
      and genetic structures of I. persulcatus and I. pavlovskyi populations inhabiting
      the southern part of Western Siberia (Russia and Kazakhstan)--the western part of
      I. pavlovskyi distribution range. The data are based on six distinct Ixodes tick
      populations. Analysis of the concatenated mitochondrial marker sequences (16S
      rRNA and COI) and the nuclear sequence (ITS2) showed genetic polymorphisms in
      both I. persulcatus and I. pavlovskyi ticks inhabiting the sympatric zone. We
      could not determine the phylogeographic structure of I. pavlovskyi populations
      whereas for I. persulcatus significant within-region variance was shown. Notably,
      the abundance of I. persulcatus ticks negatively correlates with nucleotide and
      haplotype diversity in the concatenated sequence of mitochondrial gene (16S rRNA
      and COI) fragments. This is the first description of the genetic polymorphism of
      I. persulcatus and I. pavlovskyi ticks coexisting in a sympatric zone based on
      analysis of mitochondrial and nuclear markers.

PMID- 26201400
TI  - Single-cell RNA-seq transcriptome analysis of linear and circular RNAs in mouse
      preimplantation embryos.
AB  - Circular RNAs (circRNAs) are a new class of non-polyadenylated non-coding RNAs
      that may play important roles in many biological processes. Here we develop a
      single-cell universal poly(A)-independent RNA sequencing (SUPeR-seq) method to
      sequence both polyadenylated and non-polyadenylated RNAs from individual cells.
      This method exhibits robust sensitivity, precision and accuracy. We discover 2891
      circRNAs and 913 novel linear transcripts in mouse preimplantation embryos and
      further analyze the abundance of circRNAs along development, the function of
      enriched genes, and sequence features of circRNAs. Our work is key to deciphering
      regulation mechanisms of circRNAs during mammalian early embryonic development. 

PMID- 26201401
TI  - Robot-aided in vitro measurement of patellar stability with consideration to the
      influence of muscle loading.
AB  - BACKGROUND: Anterior knee pain is often associated with patellar maltracking and
      instability. However, objective measurement of patellar stability under clinical
      and experimental conditions is difficult, and muscular activity influences the
      results. In the present study, a new experimental setting for in vitro
      measurement of patellar stability was developed and the mediolateral force
      displacement behavior of the native knee analyzed with special emphasis on
      patellar tilt and muscle loading. METHODS: In the new experimental setup, two
      established testing methods were combined: an upright knee simulator for
      positioning and loading of the knee specimens, and an industry robot for
      mediolateral patellar displacement. A minimally invasive coupling and force
      control mechanism enabled unconstrained motion of the patella as well as
      measurement of patellar motion in all six degrees of freedom via an external
      ultrasonic motion-tracking system. Lateral and medial patellar displacement were
      measured on seven fresh-frozen human knee specimens in six flexion angles with
      varying muscle force levels, muscle force distributions, and displacement forces.
      RESULTS: Substantial repeatability was achieved for patellar shift (ICC(3,1) =
      0.67) and tilt (ICC(3,1) = 0.75). Patellar lateral and medial shift decreased
      slightly with increasing flexion angle. Additional measurement of patellar tilt
      provided interesting insights into the different displacement mechanisms in
      lateral and medial directions. For lateral displacement, the patella tilted in
      the same (lateral) direction, and tilted in the opposite direction (again
      laterally) for medial displacement. With regard to asymmetric muscle loading, a
      significant influence (p < 0.03, up to 5 mm shift and 8 degrees  tilt) was found
      for lateral displacement and a reasonable relationship between muscle and
      patellar force, whereas no effect was visible in the medial direction.
      CONCLUSION: The developed experimental setup delivered reproducible results and
      was found to be an excellent testing method for the in vitro analysis of patellar
      stability and future investigation of surgical techniques for patellar
      stabilization and total knee arthroplasty. We demonstrated a significant
      influence of asymmetric quadriceps loading on patellar stability. In particular,
      increased force application on the vastus lateralis muscle led to a clear
      increase of lateral patellar displacement.

PMID- 26201403
TI  - Correlation of burnout syndrome with specific coping strategies, behaviors, and
      spiritual attitudes among interns at Yale University, New Haven, USA.
AB  - PURPOSE: This study aimed to determine the correlation of burnout syndrome with
      specific coping strategies, behaviors, and spiritual attitudes among interns in
      internal medicine, primary care, and internal medicine/pediatrics residency
      programs at two institutions. METHODS: Intern physicians completed anonymous
      voluntary surveys prior to starting the internship in June 2009 and in the middle
      of the internship in February 2010. Three validated survey instruments were used
      to explore burnout, coping, and spiritual attitudes: the Maslach Burnout
      Inventory, the COPE Inventory, and the Hatch Spiritual Involvement and Beliefs
      Scale. The interns were in programs at the Yale University School of Medicine and
      a Yale-affiliated community hospital, New Haven, Connecticut, USA. RESULTS: The
      prevalence of self-identified burnout prior to starting the internship was 1/66
      (1.5%) in June 2009, increasing to 10/53 (18.9%) in February 2010 (P<0.0001).
      From June 2009 to February 2010, the prevalence of high emotional exhaustion
      increased from 30/66 (45.5%) to 45/53 (84.9%) (P<0.0001), and that of high
      depersonalization increased from 42/66 (63.6%) to 45/53 (84.9%) (P=0.01). Interns
      who employed the strategies of acceptance and active coping were less likely to
      experience emotional exhaustion and depersonalization (P<0.05). Perceptions of
      high personal accomplishment was 75.5% and was positively correlated with total
      scores on the Hatch Spiritual Involvement and Beliefs Scale, as well as the
      internal/fluid and existential/meditative domains of that instrument. Specific
      behaviors did not impact burnout. CONCLUSION: Burnout increased during the intern
      year. Acceptance, active coping, and spirituality were correlated with less
      burnout. Specific behaviors were not correlated with burnout domains.

PMID- 26201402
TI  - Androgen Receptor Biology in Triple Negative Breast Cancer: a Case for
      Classification as AR+ or Quadruple Negative Disease.
AB  - Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that
      lacks estrogen receptor, progesterone receptor, and human epidermal growth factor
      receptor 2 (HER2) amplification. Due to the absence of these receptors, TNBC does
      not respond to traditional endocrine or HER2-targeted therapies that improve
      patient prognosis in other breast cancer subtypes. TNBC has a poor prognosis, and
      currently, there are no effective targeted therapies. Some TNBC tumors express
      androgen receptor (AR) and may benefit from AR-targeted therapies. Here, we
      review the literature on AR in TNBC and propose that TNBC be further sub
      classified as either AR+ TNBC or quadruple negative breast cancer since targeting
      AR may represent a viable therapeutic option for a subset of TNBC. 

PMID- 26201404
TI  - New dry powders for inhalation containing temozolomide-based nanomicelles for
      improved lung cancer therapy.
AB  - Besides the numerous advantages of a chemotherapy administered by the inhalation
      route for lung cancer therapy, dry powder for inhalation (DPI) offers many
      advantages compared to other techniques and seems to be a technique that is well
      adapted to an anticancer treatment. DPI formulations were developed using the
      cytotoxic drug temozolomide and a new folate-grafted self-assembling copolymer, a
      conjugate of three components, folate-polyethylene glycol-hydrophobically
      modified dextran (F-PEG-HMD). F-PEG-HMD was synthesized using carbodiimide
      mediated coupling chemistry in three main steps. F-PEG-HMD was characterized by
      1H-NMR, mass spectrometry and thermal analysis. F-PEG-HMD presented a critical
      micellar concentration in water of 4x10-7 M. F-PEG-HMD nanomicelles were
      characterized by a trimodal particle size distribution with Z-average diameter of
      83+/-1 nm in water. Temozolomide-loaded nanomicelles were prepared by
      solubilization of F-PEG-HMD in the presence of temozolomide. Temozolomide
      solubility in water was increased in the presence of F-PEG-HMD (2-fold increase
      in molar solubility) which could potentially lead to increased local
      concentrations in the tumor site. The temozolomide-loaded F-PEG-HMD nanomicelles
      were characterized by a Z-average diameter of ~50 to ~60 nm, depending on the F
      PEG-HMD concentration used. The nanomicelles were then spray-dried to produce dry
      powders. Temozolomide remained stable during all the formulation steps, confirmed
      by similar in vitro anticancer properties for the DPI formulations and a raw
      temozolomide solution. Two of the developed DPI formulations were characterized
      by good aerodynamic properties (with a fine particle fraction of up to 50%) and
      were able to release the F-PEG-HMD nanomicelles quickly in aqueous media.
      Moreover, in vitro, the two DPI formulations showed wide pulmonary deposition in
      the lower respiratory tract where adenocarcinomas are more often found. The
      present study, therefore, shows that F-PEG-HMD-based dry powders for inhalation
      could constitute an interesting drug delivery system able to release nanomicelles
      that are useful in adenocarcinomas that overexpress folate receptors. 

PMID- 26201406
TI  - The long way toward understanding host and viral determinants of therapeutic
      success in HCV infection.

PMID- 26201407
TI  - Effects of anthocyanins from purple sweet potato (Ipomoea batatas L. cultivar
      Eshu No. 8) on the serum uric acid level and xanthine oxidase activity in
      hyperuricemic mice.
AB  - This study was aimed at evaluating the hypouricemic effect of the anthocyanin
      rich purple sweet potato extract (APSPE). In vitro, APSPE has been proved to
      significantly inhibit XO activity in a dose-dependent manner. In vivo, APSPE
      could not only inhibit the XO activity in mouse liver, but also reduce the serum
      uric acid level in hyperuricemic mice and affect the expression of mRNA levels of
      related renal transporters, such as mURAT1, mGLUT9, mOAT1 and mOCTN2. Moreover,
      APSPE could effectively regulate BUN and Cr levels to normal and decrease the
      inflammatory cellular influx in the tubule of the hyperuricemic mice. This study
      indicates the potential clinical utility of APSPE as a safe and effective anti
      hyperuricemia bioactive agent or functional food. 

PMID- 26201408
TI  - Adaptable, high recall, event extraction system with minimal configuration.
AB  - BACKGROUND: Biomedical event extraction has been a major focus of biomedical
      natural language processing (BioNLP) research since the first BioNLP shared task
      was held in 2009. Accordingly, a large number of event extraction systems have
      been developed. Most such systems, however, have been developed for specific
      tasks and/or incorporated task specific settings, making their application to new
      corpora and tasks problematic without modification of the systems themselves.
      There is thus a need for event extraction systems that can achieve high levels of
      accuracy when applied to corpora in new domains, without the need for exhaustive
      tuning or modification, whilst retaining competitive levels of performance.
      RESULTS: We have enhanced our state-of-the-art event extraction system,
      EventMine, to alleviate the need for task-specific tuning. Task-specific details
      are specified in a configuration file, while extensive task-specific parameter
      tuning is avoided through the integration of a weighting method, a covariate
      shift method, and their combination. The task-specific configuration and
      weighting method have been employed within the context of two different sub-tasks
      of BioNLP shared task 2013, i.e. Cancer Genetics (CG) and Pathway Curation (PC),
      removing the need to modify the system specifically for each task. With minimal
      task specific configuration and tuning, EventMine achieved the 1st place in the
      PC task, and 2nd in the CG, achieving the highest recall for both tasks. The
      system has been further enhanced following the shared task by incorporating the
      covariate shift method and entity generalisations based on the task definitions,
      leading to further performance improvements. CONCLUSIONS: We have shown that it
      is possible to apply a state-of-the-art event extraction system to new tasks with
      high levels of performance, without having to modify the system internally. Both
      covariate shift and weighting methods are useful in facilitating the production
      of high recall systems. These methods and their combination can adapt a model to
      the target data with no deep tuning and little manual configuration.

PMID- 26201405
TI  - APASL consensus statements and management algorithms for hepatitis C virus
      infection.
AB  - The Asian Pacific Association for the Study of the Liver (APASL) convened an
      international working party on the "APASL Consensus Statements and Management
      Algorithms for Hepatitis C Virus Infection" in December, 2010, in order to revise
      "Asian Pacific Association for the Study of the Liver consensus statements on the
      diagnosis, management and treatment of hepatitis C virus infection (J
      Gastroenterol Hepatol 22:615-633, 2007)". The working party consisted of expert
      hepatologists from the Asian-Pacific region gathered at Makuhari, Chiba, Japan on
      19 December 2010. New data were presented, discussed and debated to draft a
      revision. Participants of the consensus meeting assessed the quality of cited
      studies. Finalized recommendations are presented in this review. 

PMID- 26201410
TI  - Objective assessment of robotic surgical skill using instrument contact
      vibrations.
AB  - BACKGROUND: Surgical skill evaluation ordinarily requires tedious video review
      and survey completion, while new automatic approaches focus on evaluating the
      quality of the surgeon's movements in free space. Robotic surgical instrument
      vibrations are simple to measure and physically correspond to how roughly
      instruments are handled, but they have yet to be studied as a measure of
      technical surgical skill. METHODS: Thirteen surgeons used a robotic surgery
      system (da Vinci S by Intuitive Surgical) to perform four trials each of peg
      transfer (PT), needle pass (NP), and intracorporeal suturing (IS). Completion
      time, instrument vibrations, and applied forces were measured for each trial;
      root mean square (RMS) and total sum of squares (TSS) were calculated from both
      the vibration and force recordings. Four experienced surgeons blindly assessed
      the task videos using a Global Rating Scale (GRS), and skill metrics were
      compared between the eight novices and five experienced participants. Stepwise
      regression was performed to predict GRS score from objective skill metrics. The
      concurrent validity of each metric was evaluated using receiver operating
      characteristic (ROC) analysis. RESULTS: The GRS demonstrated excellent internal
      consistency (Cronbach's alpha = 0.91) and strong inter-rater reliability (ICC =
      0.84). Compared to novices, experienced surgeons earned higher GRS scores and
      performed tasks with lower vibration magnitudes, lower forces, and shorter
      completion times in 15 of 18 task-metric combinations (p values ranging from
      0.042 to <0.001). ROC analysis demonstrated that including vibration and force
      magnitudes along with completion time in skill prediction models improves the
      objective classification of subjects as novice or experienced for all tasks
      studied (PT: 90% sensitivity, 75% specificity; NP: 85% sensitivity, 84%
      specificity; suturing: 100% sensitivity, 100% specificity). CONCLUSIONS: RMS and
      TSS instrument vibrations are novel construct-valid measures of robotic surgical
      skill that enable the development of objective skill assessment models comparable
      to observer-based ratings.

PMID- 26201411
TI  - Effectiveness of Surgicel(r) (Fibrillar) in patients with colorectal endoscopic
      submucosal dissection.
AB  - BACKGROUND AND AIMS: Because the invasive procedure of colorectal endoscopic
      submucosal dissection (ESD) entails a extensive mucosal defect and submucosal
      exposure, the procedure may have a substantial risk of complications including
      delayed bleeding, perforation and bacteremia and/or endotoxemia. The aim of our
      study was to investigate whether Surgicel((r)) would be effective in reducing
      complications after colorectal ESD. PATIENTS AND METHODS: Between 2012 and 2013,
      52 consecutive patients who underwent a colorectal ESD were enrolled. After the
      removal of colorectal epithelial neoplasm, surgicel was sprayed onto the
      submucosal surface using the wet type of application (Surgicel((r)) group). We
      evaluated tumor type, location, size, histology, procedure time, hospital stay
      and associated complication. For assessing inflammatory reaction, white blood
      cells and body temperature were monitored. In assessing the effectiveness of
      Surgicel((r)) application, we retrospectively compared the clinical outcomes with
      52 other consecutive large colorectal tumor patients who had previously received
      conventional ESD, as control group (non-Surgicel((r)) group). RESULTS: Of the 52
      patients, three patients were excluded. Forty-nine patients were ultimately
      enrolled in this study. During the follow-up period, rebleeding occurred in 0 (0%
      in Surgicel((r)) group) patients and 4 (7.7% in non-Surgicel((r)) group)
      patients; fever (>37.7) in 2 (4.1%) and 10 (19.2%) patients, respectively (p =
      0.019); and leukocytosis in 9 (18.4%) and 16 (30.8%) patients, respectively (p =
      0.172). C-reactive protein level was 0.35 +/- 0.18 and 9.83 +/- 2.44 (p < 0.001).
      The mean hospitalization period was 4.22 +/- 0.94 and 5.13 +/- 0.27 days,
      respectively (p < 0.001). The group (surgicel vs. non-surgicel, p = 0.005, odds
      ratio 11.114 (2.104-58.718)) was identified as independent predictor for
      complication such as fever or delayed bleeding by multivariated analysis.
      CONCLUSIONS: Surgicel((r)) application after colorectal ESD may be an effective
      method to reduce some complications and mean hospitalization period. Therefore,
      surgicel application may be considered to be a valuable clinical method.

PMID- 26201412
TI  - Lap band outcomes from 19,221 patients across centers and over a decade within
      the state of New York.
AB  - INTRODUCTION: We sought to determine the rate of revision and explant of the
      laparoscopic adjustable gastric banding (LAGB) over a ten-year period in the
      state of New York. METHODS: Following IRB approval, the SPARCS administrative
      database was used to identify LAGB placement from 2004 to 2010. We tracked
      patients who underwent band placement with subsequent removal/revision, followed
      by conversion to either Roux-en-Y gastric bypass (RYBG) or sleeve gastrectomy
      (SG) between 2004 and 2013. McNemar test and Chi-square test were used to compare
      complications between primary procedure and subsequent revision and to compare
      complication rates and mortality rates, respectively. Log-rank test was used to
      assess patient characteristics and comorbidities. p < 0.05 was considered
      significant. RESULTS: During a 7-year period, there were 19,221 records of LAGB
      placements and 6567 records of revisions or removal. We were able to follow up
      3158 (16.43 %) who subsequently underwent a band removal or revision over the
      course of this period. An additional 3606 patients had no records in the state of
      New York following the procedure, thus making the rate of revision 20.22 %.
      Initial revision procedures were coded as band removal in 32.77 % (n = 1035),
      band revision in 30.53 % (n = 964), band removal and replacement in 19.09 % (n =
      603), removal and conversion to SG in 5.64 % (n = 178), or removal and conversion
      to RYGB in 11.97 % (n = 378). From the 3158 patients, 2515 (79.64 %) required
      only one revision. Six hundred and forty-three patients underwent two or more
      revisions. Thirty-one out of 3158 (0.0098 %) patients had complications at their
      initial operation, but 919 (29.1 %) had complications during revision (p <
      0.0001). CONCLUSIONS: Over a 7-year period, at least 20.22 % of LAGB required
      removal or revision. Based on all case numbers, total revision rate may be as
      high as 34.2 %. Although the band is believed to be a reversible procedure,
      revisional procedures are significantly more morbid than the initial procedure.

PMID- 26201413
TI  - Percutaneous aspiration of the gall bladder for the treatment of acute
      cholecystitis: a prospective study.
AB  - BACKGROUND: Urgent laparoscopic cholecystectomy has been established as the best
      treatment for acute cholecystitis. However, conservative treatment is advocated
      for high-risk patients. Failure of conservative treatment can result in high-risk
      operations with relatively high rates of operative morbidity. Percutaneous
      cholecystostomy is a good option for these patients. Recently, percutaneous
      aspiration of the gall bladder without drain has been described. METHODS: A
      protocol of initial conservative management in high-operative-risk patients
      admitted with acute cholecystitis was prospectively assessed. Patients who did
      not respond to antibiotics were treated with percutaneous trans-hepatic
      aspiration of the gall bladder under ultrasound guidance. Following discharge,
      the patients were seen in the outpatient clinic and elective laparoscopic
      cholecystectomy was considered and scheduled as necessary. RESULTS: Between
      January 2011 and December 2012, 33 patients with persistent clinical and
      sonographic signs of acute cholecystitis after failure of initial antibiotic
      treatment underwent gall bladder aspiration under ultrasound guidance. No
      complications related to the procedure were reported. In 25 patients (76 %), the
      procedure was successful and they were discharged. Seven patients needed repeated
      aspiration. Eight patients (24 %) who did not improve underwent percutaneous
      cholecystostomy and were discharged with a drain and later reevaluated for
      elective surgery. The mean hospital stay of patients with successful aspiration
      was 3 days. During the follow-up period, 23 patients underwent elective interval
      laparoscopic cholecystectomy. Two were converted to open surgery (8.7 %).
      CONCLUSIONS: Conservative treatment and delayed operation is an acceptable option
      for acute cholecystitis. Percutaneous gall bladder aspiration is a simple and
      effective procedure, with a high success rate and low morbidity. Laparoscopic
      cholecystectomy after drainage of the gall bladder has low morbidity with a
      relatively low conversion rate.

PMID- 26201414
TI  - Eleven years of primary closure of common bile duct after choledochotomy for
      choledocholithiasis.
AB  - BACKGROUND: The choice of surgical technique to extract stones from the common
      bile duct (CBD) depends on local experience, anatomical characteristics and also
      on the size, location and number of stones. Most authors consider choledochotomy
      an alternative to failed transcystic exploration, although some use it
      exclusively. Although the CBD is traditionally closed with T-tube drainage after
      choledochotomy, its use is associated with 11.3-27.5 % morbidity. This study
      examined the efficacy of laparoscopic CBD exploration (LCBDE) with primary
      closure for the treatment of CBD stones using intraoperative cholangiography
      (IOC). METHODS: Retrospective study of 160 patients who underwent LCBDE with
      primary closure after choledochotomy between January 2001 and December 2012.
      RESULTS: The diagnosis of choledocholithiasis was definitively made in all cases
      by IOC. The overall complication rate was 15 % and the biliary complication rate
      was 7.5 %. Bile leakage was reported in 11 patients (6.8 %). In over half the
      cases (63.6 %), no further action was required and the leak closed spontaneously.
      Six patients were reoperated (3.75 %), two for bile peritonitis and four for
      haemoperitoneum. The success rate for stone clearance was 96.2 %. The mortality
      rate and CBD stricture rate were 0 %. CONCLUSION: Primary closure after
      choledochotomy to clear stones from the CBD is a safe technique that confers
      excellent results and allows one-stage treatment.

PMID- 26201416
TI  - Esophagogastric junction distensibility measured by a functional lumen imaging
      probe with incremental gastric myotomy lengths in achalasia.

PMID- 26201415
TI  - First-line endoscopic treatment with OTSC in patients with high-risk non-variceal
      upper gastrointestinal bleeding: preliminary experience in 40 cases.
AB  - BACKGROUND AND STUDY AIMS: The over-the-scope clip (OTSC; Ovesco, Tubingen,
      Germany) is a novel endoscopic clipping device designed for tissue approximation.
      The device has been used in the closure of fistulas and perforations. We hereby
      report a series of patients with high-risk non-variceal upper gastrointestinal
      bleeding (NVUGIB) lesions in whom OTSCs were used as first-line endoscopic
      treatment. PATIENTS AND METHODS: We prospectively collected and retrospectively
      analysed data over a period of 12 months from October 2013 to November 2014 from
      all consecutive patients who underwent emergency endoscopy for acute severe high
      risk NVUGIB and were treated with OTSC as primary first-line therapy. RESULTS: We
      included forty consecutive patients with mean age 69 years (range 25-94 years).
      All patients were treated with the non-traumatic version of the OTSC system (23
      with the 11 mm version and 17 with the 12 mm version). Indications for OTSC
      treatment included gastric ulcer with large vessel (Forrest IIa) (n = 8, 20 %),
      duodenal ulcer (Forrest Ib) (n = 7, 18 %), duodenal ulcer with large vessel
      (Forrest IIa) (n = 6, 15 %), Dieulafoy's lesion (n = 6, 15 %) and other secondary
      indications (n = 13, 32 %). Technical success and primary haemostasis were
      achieved in all patients (100 %). No re-bleeding, need for surgical or
      radiological embolization treatment or other complications were observed during
      the follow-up period of 30 days. CONCLUSIONS: We conclude OTSC placement as a
      first-line endoscopic treatment seems to be effective, safe and easy to perform
      and should be considered in patients with high-risk NVUGIB lesions.

PMID- 26201417
TI  - Totally laparoscopic spleen-preserving splenic hilum lymph nodes dissection in
      radical total gastrectomy: an omnibearing method.
AB  - OBJECTIVE: To investigate the feasibility and safety of laparoscopic spleen
      preserving splenic hilum lymph nodes (LNs) dissection for advanced proximal
      gastric cancer using an omnibearing method. METHODS: Between August 2013 and
      December 2014, 16 patients with advanced proximal gastric cancer treated in
      Guangdong Province Hospital of Chinese Medicine, were enrolled and subsequently
      underwent laparoscopic radical total gastrectomy (TG) with spleen-preserving
      splenic hilum LNs dissection. During dissecting Nos. 10 and 11 LNs, we divided
      them into two parts, namely LNs anterosuperior and posterior to the splenic
      vessel. The clinicopathological characteristics, intraoperative outcomes and
      postoperative courses were retrospectively collected and analyzed in the study.
      RESULTS: Laparoscopic surgery was successfully completed in all 16 patients
      without conversion to open surgery, and no perioperative death occurred. The mean
      operating time was 328.75 +/- 46.96 min, and the mean estimated blood loss was
      135.63 +/- 62.07 ml. One patient experienced intraoperative bleeding due to the
      splenic vein injury which was successfully handled with laparoscopic vessel
      suturing, and one postoperative pulmonary infection was recorded. The mean time
      to first flatus was 3.56 +/- 1.03 days with a mean 9.63 +/- 1.50 days of
      postoperative hospital stay. The mean number of retrieved LNs was 28.31 +/- 5.99,
      in which LNs anterosuperior to splenic artery was 2.88 +/- 2.66 and LNs posterior
      was 1.38 +/- 1.75. CONCLUSION: Laparoscopic TG with spleen-preserving splenic
      hilum LNs dissection using an omnibearing method for advanced proximal gastric
      cancer was safe and technically feasible in experienced hands. Further studies in
      terms of its clinical significance are needed.

PMID- 26201419
TI  - Isotopic variation in five species of stream fishes under the influence of
      different land uses.
AB  - The aim of this study was to test if changes in land use alter the isotopic
      signature of fish species, promoting changes in the trophic position and food
      resource partitioning between these consumers. Three different systems were
      investigated: pasture streams (n = 3), streams in sugar cane plantations (n = 3)
      and reference streams (n = 3). Fish species Aspidoras fuscoguttatus, Astyanax
      altiparanae, Characidium zebra, Hisonotus piracanjuba and Knodus moenkhausii were
      selected, and their nitrogen and carbon isotopic compositions were estimated to
      assess changes in the trophic level and partitioning of food items consumed. The
      composition of delta(13) C (0/00) only differed among the land use categories for
      A. altiparanae, H. piracanjuba and K. moenkhausii. Resource partitioning was
      different for all species, with changes in the sources or proportions they
      consumed in each land use category, but only A. altiparanae introduced new food
      sources in large quantity in altered land uses. It is important to note, however,
      that the results from the resource partitioning analysis are limited due to large
      overlapping of isotopic signatures between the analysed food resources. All fish
      species exhibited variation in delta(15) N (0/00), with the highest values found
      in streams under sugar cane or pasture influence. Despite the variation in
      nitrogen isotopic values, only C. zebra and H. piracanjuba displayed changes in
      trophic level. Therefore, it is believed that the increase in the delta(15) N
      (0/00) value of the individuals collected in streams under the influence of sugar
      cane or pasture was due to the greater influence of livestock dung and chemical
      and organic fertilizers. The results also highlight the importance of studying
      consumer species along with all forms of resources available at each location
      separately, because the signatures of these resources also vary within different
      land uses.

PMID- 26201418
TI  - Long-term outcomes of percutaneous endoscopic intragastric surgery in the
      treatment of gastrointestinal stromal tumors at the esophagogastric junction.
AB  - BACKGROUND: The treatment options for gastrointestinal stromal tumors (GITSs) at
      the esophagogastric junction (EGJ) are controversial. There have been reports on
      enucleation for EGJ GISTs in order to avoid gastrectomy. But the number of
      patients is too small, or the follow-up period is too short to evaluate it. The
      purpose of this study was to review our experience of 59 patients with EGJ GISTs
      treated by enucleation by percutaneous endoscopic intragastric surgery (PEIGS)
      and assess the clinical outcomes. METHODS: PEIGS is performed as described below.
      Access ports are placed through the abdominal wall and the anterior wall of the
      stomach. Through the access ports, an endoscope and surgical instruments are
      inserted into the gastric lumen and tumor enucleation and closure of the defect
      are carried out. In this study, 59 patients with EGJ GISTs treated by PEIGS
      between 2005 and 2013 were enrolled. Their hospital records were reviewed, and
      follow-up data for 8 years were collected to analyze the outcomes. RESULTS: En
      bloc enucleation was achieved without tumor rupture in all. Average operation
      time was 172.3 min. Postoperative complications occurred in 3 (one localized
      peritonitis, one bleeding, and one surgical site infection). Average tumor size
      was 35.6 mm. Pathological findings confirmed negative margin in all specimens.
      The maximum follow-up period was 101 months. Multiple liver metastases were
      detected in two patients (at 12 and 29 months). The survival rate was 100 %. The
      disease-free rate was 98.3 % at 12 months and 96.6 % at 29 months, respectively.
      CONCLUSIONS: As far as the short- and long-term outcomes of our experience are
      reviewed, PEIGS seems as curative as other aggressive resection methods such as
      proximal gastrectomy. Tumor enucleation by PEIGS, offering a chance to preserve
      the stomach, can be a preferable option in carefully selected patients with EGJ
      GISTs, when performed by a skilled surgeon.

PMID- 26201420
TI  - John Charnley Award: Preoperative Patient-reported Outcome Measures Predict
      Clinically Meaningful Improvement in Function After THA.
AB  - BACKGROUND: Despite the overall effectiveness of total hip arthroplasty (THA), a
      subset of patients remain dissatisfied with their results because of persistent
      pain or functional limitations. It is therefore important to develop predictive
      tools capable of identifying patients at risk for poor outcomes before surgery.
      QUESTIONS/PURPOSES: The purpose of this study was to use preoperative patient
      reported outcome measure (PROM) scores to predict which patients undergoing THA
      are most likely to experience a clinically meaningful change in functional
      outcome 1 year after surgery. METHODS: A retrospective cohort study design was
      used to evaluate preoperative and 1-year postoperative SF-12 version 2 (SF12v2)
      and Hip Disability and Osteoarthritis Outcome Score (HOOS) scores from 537
      selected patients who underwent primary unilateral THA. Minimum clinically
      important differences (MCIDs) were calculated using a distribution-based method.
      A receiver operating characteristic analysis was used to calculate threshold
      values, defined as the levels at which substantial changes occurred, and their
      predictive ability. MCID values for HOOS and SF12v2 physical component summary
      (PCS) scores were calculated to be 9.1 and 4.6, respectively. We analyzed the
      effect of SF12v2 mental component summary (MCS) scores, which measure mental and
      emotional health, on SF12v2 PCS and HOOS threshold values. RESULTS: Threshold
      values for preoperative HOOS and PCS scores were a maximum of 51.0 (area under
      the curve [AUC], 0.74; p < 0.001) and 32.5 (AUC, 0.62; p < 0.001), respectively.
      As preoperative mental and emotional health improved, which was reflected by a
      higher MCS score, HOOS and PCS threshold values also increased. When preoperative
      mental and emotional health were taken into account, both HOOS and PCS threshold
      values' predictive ability improved (AUCs increased to 0.77 and 0.69,
      respectively). CONCLUSIONS: We identified PROM threshold values that predict
      clinically meaningful improvements in functional outcome after THA. Patients with
      a higher level of preoperative function, as suggested by HOOS or PCS scores above
      the defined threshold values, are less likely to obtain meaningful improvement
      after THA. Lower preoperative mental and emotional health decreases the
      likelihood of achieving a clinically meaningful improvement in function after
      THA. The results of this study may be used to facilitate discussion between
      physicians and patients regarding the expected benefit after THA and to support
      the development of patient-based informed decision-making tools. For example,
      despite significant disease, patients with high preoperative function, as
      measured by PROM scores, may choose to delay surgery given the low likelihood of
      experiencing a meaningful improvement postoperatively. Similarly, patients with
      notably low MCS scores might best be counseled to address mental health issues
      before embarking on surgery. LEVEL OF EVIDENCE: Level III, prognostic study.

PMID- 26201421
TI  - D-amino acid inhibits biofilm but not new bone formation in an ovine model.
AB  - BACKGROUND: Infectious complications of musculoskeletal trauma are an important
      factor contributing to patient morbidity. Biofilm-dispersive bone grafts
      augmented with D-amino acids (D-AAs) prevent biofilm formation in vitro and in
      vivo, but the effects of D-AAs on osteocompatibility and new bone formation have
      not been investigated. QUESTIONS/PURPOSES: We asked: (1) Do D-AAs hinder
      osteoblast and osteoclast differentiation in vitro? (2) Does local delivery of D
      AAs from low-viscosity bone grafts inhibit new bone formation in a large-animal
      model? METHODS: Methicillin-sensitive Staphylococcus aureus and methicillin
      resistant S aureus clinical isolates, mouse bone marrow stromal cells, and
      osteoclast precursor cells were treated with an equal mass (1:1:1) mixture of D
      Pro:D-Met:D-Phe. The effects of the D-AA dose on biofilm inhibition (n = 4),
      biofilm dispersion (n = 4), and bone marrow stromal cell proliferation (n = 3)
      were quantitatively measured by crystal violet staining. Osteoblast
      differentiation was quantitatively assessed by alkaline phosphatase staining, von
      Kossa staining, and quantitative reverse transcription for the osteogenic factors
      a1Col1 and Ocn (n = 3). Osteoclast differentiation was quantitatively measured by
      tartrate-resistant acid phosphatase staining (n = 3). Bone grafts augmented with
      0 or 200 mmol/L D-AAs were injected in ovine femoral condyle defects in four
      sheep. New bone formation was evaluated by MUCT and histology 4 months later. An
      a priori power analysis indicated that a sample size of four would detect a 7.5%
      difference of bone volume/total volume between groups assuming a mean and SD of
      30% and 5%, respectively, with a power of 80% and an alpha level of 0.05 using a
      two-tailed t-test between the means of two independent samples. RESULTS: Bone
      marrow stromal cell proliferation, osteoblast differentiation, and osteoclast
      differentiation were inhibited at D-AAs concentrations of 27 mmol/L or greater in
      a dose-responsive manner in vitro (p < 0.05). In methicillin-sensitive and
      methicillin-resistant S aureus clinical isolates, D-AAs inhibited biofilm
      formation at concentrations of 13.5 mmol/L or greater in vitro (p < 0.05). Local
      delivery of D-AAs from low-viscosity grafts did not inhibit new bone formation in
      a large-animal model pilot study (0 mmol/L D-AAs: bone volume/total volume =
      26.9% +/- 4.1%; 200 mmol/L D-AAs: bone volume/total volume = 28.3% +/- 15.4%;
      mean difference with 95% CI = -1.4; p = 0.13). CONCLUSIONS: D-AAs inhibit biofilm
      formation, bone marrow stromal cell proliferation, osteoblast differentiation,
      and osteoclast differentiation in vitro in a dose-responsive manner. Local
      delivery of D-AAs from bone grafts did not inhibit new bone formation in vivo at
      clinically relevant doses. CLINICAL RELEVANCE: Local delivery of D-AAs is an
      effective antibiofilm strategy that does not appear to inhibit bone repair.
      Longitudinal studies investigating bacterial burden, bone formation, and bone
      remodeling in contaminated defects as a function of D-AA dose are required to
      further support the use of D-AAs in the clinical management of infected open
      fractures.

PMID- 26201423
TI  - CORR Insights((r)): do alumina matrix composite bearings decrease hip noises and
      bearing fractures at a minimum of 5 years after THA?

PMID- 26201422
TI  - Backside Wear Is Not Dependent on the Acetabular Socket Design in Crosslinked
      Polyethylene Liners.
AB  - BACKGROUND: Although it is understood that backside damage occurs in polyethylene
      acetabular liners, the effect of highly crosslinked polyethylene, which has
      completely replaced conventional polyethylene, has yet to be examined.
      QUESTIONS/PURPOSES: The purpose of this study was to answer the following
      questions: (1) With conventional polyethylene (CPE), did the acetabular design
      make a difference in backside wear? (2) Is there a difference in backside damage
      between CPE and crosslinked polyethylene (XLPE) liners? (3) With XLPE, is the
      difference in backside wear between designs still present? (4) Is there any
      difference in backside damage in various zones on backside of individual liners?
      METHODS: This single-institution retrieval analysis involved visual damage
      scoring on the backside of 233 polyethylene liners implanted between 2002 and
      2011. The liners were retrieved from either polished/dovetail cups (PD) or
      roughened/wire cups (RW) made by two different manufacturers. The inserts were
      divided into four groups: PD-CPE (n = 105), PD-XLPE (n = 16), RW-CPE (n = 99),
      and RW-XLPE (n = 13). Aseptic loosening and polyethylene wear were the
      predominant reasons for revision of CPE liners, whereas instability and infection
      were the common reasons for revision of XLPE liners. The time in situ (TIS) was
      shorter for the XLPE liners as compared with the CPE liners (PD-CPE: 8.5 years
      [SD 4.4]; RD-CPE: 9.5 [SD 4.8]; PD-CPE: 3.8 [SD 3.7]; RD-XLPE: 4.0 [SD 4.3]). The
      backside of each liner was divided into five zones and graded initially from a
      scale of 0 to 3 for seven different damage modes by one observer. There was
      substantial interobserver (kappa 0.769) and intraobserver (0.736) reliability on
      repeat scoring. To compare the effects of crosslinking, a subset of the
      conventional polyethylene liners was matched to the crosslinked liners based on
      TIS, resulting in 16 per group for the two PD types and 13 per group for the two
      RW types. RESULTS: Total damage scores in the RW-CPE (19 +/- 7) group were
      greater (p < 0.001) than the PD-CPE group (8 +/- 4). Damage was reduced with XLPE
      (p = 0.02) only for the RW-XLPE (9 +/- 9) versus RW-CPE-type sockets (4 +/- 4).
      There was no difference (p = 0.16) between the RW-XLPE group and the PD-XLPE
      group. Damage scores in the peripheral zone of the locking mechanisms were higher
      for RW-CPE (4 +/- 3) compared with PD-CPE (1.4 +/- 1.0, p < 0.001) and RW-XLPE
      (1.3 +/- 1.3, p = 0.02). Damage was greater (p < 0.001) within the superior zones
      (7 +/- 4) compared with the inferior zones (3.0 +/- 2.8) of all liners.
      CONCLUSIONS: The current study shows greater backside damage for CPE in the
      roughened, wire lock cups. XLPE was shown to be more resistant to backside damage
      for both socket designs. CLINICAL RELEVANCE: Although the polished/dovetail cups
      seem to cause less backside damage in the CPE liners than roughened/wire cups,
      the use of XLPE liners has been shown to protect the liner from backside damage
      in either cup design. If an acetabular shell has a functional locking mechanism,
      surgeons should not worry about cup design when undertaking isolated liner
      revision using XLPE liners.

PMID- 26201424
TI  - The high reutilization value potential of high-salinity anchovy fishmeal
      wastewater through microbial degradation.
AB  - To provide an option for the reutilization of high-salinity anchovy fishmeal
      wastewater (FMW), generated during the anchovy fishmeal manufacturing processes,
      its potential for biodegradation was assessed in 1-l five-neck flasks using a
      halotolerant and proteolytic microbial consortium. During the first 41 h of
      biodegradation, the pH, DO, ORP, and dry-sludge weight decreased as the total
      cell number of the microbial consortium increased steadily; the COD(Cr)/TN ratios
      remained between 4.0 and 5.5, respectively, indicating the stable metabolic
      degradation of organic matter. The ORP tended to increase after 41 h, and the
      unpleasant fishy smell disappeared once positive ORP values were achieved. The
      removal percentages of COD(Cr) and TN were 59.0 and 54.4%, respectively, and the
      dry-sludge weight decreased from 115.5 to 68.0 g, with a degradation rate of 0.59
      g h(-1), during the 80 h experiment. The supernatant from the culture of the
      anchovy FMW at 70 h (culture supernatant) was phytotoxin-free, and the level of
      total amino acids was 8.04 g 100 g(-1), comparable to that of commercial
      fertilizers. In hydroponic cultures containing red bean and barley, the culture
      supernatant demonstrated a good fertilizing ability. The culture supernatant also
      exhibited a high degree of antioxidant activity, with a 52.3% hydroxyl radical
      scavenging activity and 0.16 reducing power (at OD 700 nm). Moreover, the culture
      supernatant inhibited DNA damage from hydroxyl radicals, enhancing the
      reutilization value of anchovy FMW. This report presents the first description of
      high-salinity anchovy FMW possessing a high reutilization value potential both
      for agriculture and medicine.

PMID- 26201426
TI  - Self-care Improvement After a Pharmaceutical Intervention in Elderly Type 2
      Diabetic Patients.
AB  - Diabetes mellitus involves long-term complications that affect diabetic patients'
      quality of life. The best way to prevent these complications is that patients
      achieve good metabolic control. In order to reach this goal, patients are
      requested to acquire daily behaviours (self-care). Such behaviours are sometimes
      hard to adhere, because they require changes in habits acquired over time. The
      aim of the present study is to evaluate the improvement on self-care after a
      pharmaceutical intervention on home regime patients. We performed a controlled
      experimental comparative study with a follow up of 6 months, on 87 patients,
      randomized in control group (n=43) and intervention group (n=44). We accessed
      sociodemographic and clinical data (glycaemic profile), as well as adherence to
      drug therapy and self-assessed care (before/after). In the intervention group,
      mean age was 74.2+/-5.4 years, and the median time of T2DM diagnosis was 14.7+/
      8.5 years. At the end of study, the decrease in fasting blood glucose was higher
      in the intervention group patients than that observed in the control group
      (50.2mg/dL), with statistically significant difference (p<0.05), as well as the
      decrease verified in HbA1c. In self-care adherence, alterations in the levels of
      adherence of the general nutrition and physical exercise dimensions became
      evident, with an increase in the number of days of adherence. On medication
      adherence statistically significant alterations (p<0.05) were also recorded. We
      can conclude that an individualized pharmaceutical intervention can improve self
      care behaviours, as well as medication adherence, contributing to better
      metabolic control.

PMID- 26201427
TI  - Functional Aspects in Ageing Adults with Diabetic Neuropathy. A Review.
AB  - Diabetic Peripheral Neuropathy (DPN) is highly prevalent among diabetic ageing
      adults. The sensory and motor impairments caused by this long-term complication
      lead to poorer physical functioning, postural control and balance. These changes
      affect the activities of daily living and increase the risk of falling,
      subsequently leading to increased morbidity and decreased quality of life. Early
      detection of such functional limitations is important, as it may influence the
      effectiveness of rehabilitation programs and prevent further functional
      dependence. This review focuses on functional aspects related to balance,
      postural control and mobility in ageing adults suffering from DPN, as well as
      their assessment by valid, reliable and low-cost performance-based measurements.
      PUBMED was searched for articles in English published between 2004 and 2014.
      Search terms included diabetic neuropathy, balance, postural control, functional
      mobility, and functional outcomes. Reviewed literature indicates that simple and
      low-cost measurements, easy to include in clinical routines, can be used for
      screening impairments in complex functions, such as balance and mobility. Some
      studies have also been able to correlate results from DPN severity scales with
      those of functional tests, showing that applying such tests may improve the early
      diagnosis of this neurological disorder. Berg Balance Scale, Dynamic Gait Index,
      Functional Reach Test, and Time Up and Go already have modified cut-off points
      for the Diabetes Mellitus older population, but need validation for ageing adults
      with DPN. Further research on this subject should be addressed, in order to
      improve assessment outcomes. 

PMID- 26201425
TI  - Decreased expression of MicroRNA-200 family in human breast cancer is associated
      with lymph node metastasis.
AB  - OBJECTIVES: MicroRNA-200 family (miR-200f) has been consistently reported to be
      deregulated and modulate the metastatic process in multiple cancers. In the
      present study, we detected the expression of miR-200f in breast cancer (BC)
      tissue and explored its relationships with clinicopathological characteristics,
      especially with lymph node metastasis. METHODS: Expression levels of miR-200a,
      miR-200b, miR-200c, miR-141, and miR-429 in 99 pairs of BC tissues and adjacent
      normal tissues were measured by real-time quantitative PCR. The correlation
      between miR-200f level and multiple clinicopathological factors was then examined
      by Mann-Whitney test, ANOVA, and operating characteristic (ROC) analysis.
      RESULTS: All members of the miR-200f were down-regulated in BC tissue compared
      with that in normal adjacent tissue; miR-200a, miR-200b, and miR-200c were highly
      decreased (p < 0.05), while the differences of miR-141 and miR-429 between
      patients and the control group were not statistically significant. Furthermore,
      all five members were found to be distinctly decreased with the incidence of
      lymph node metastasis (p < 0.05); When the patients were divided into three
      groups according to the number of lymph node metastasis (0; 1-3; >=4), a gradual
      decrease of miR-200f expression was observed with the increasing number of lymph
      node metastasis; ROC revealed that miR-200b can differentiate patients with lymph
      node metastasis from those without lymph node metastasis. CONCLUSION: These
      observations imply that the down-regulation of miR-200f in human BC is associated
      with an invasive phenotype, and miR-200b may be useful to estimate the likelihood
      of the presence of pathologically positive lymph nodes.

PMID- 26201428
TI  - Ageing and Nutritional Therapy Adherence in Type 2 Diabetes.
AB  - The prevalence of diabetes increases with age, which is also a determinant of
      nutrition therapy adherence. This descriptive study was conducted in a non-random
      sample of 66 patients aged between 47 and 75 years (M=61.5; SD=8.0) receiving
      health care in a Diabetes Clinic in the municipality of Faro, in the Portuguese
      region of the Algarve. We aimed to assess the association between age and the
      clinical characteristics of type 2 diabetes and to analyze the perceptions
      regarding the barriers to an adequate diet. Glycated hemoglobin (HbA1c) (r=
      0.372, P<0.001) showed a negative correlation with age, suggesting that older
      patients have a better glucose control. Older age is also correlated with a
      higher number of daily meals (r=0.263) and lower intake of energy (r=-0.334),
      protein (r=-0.249), sugars (r=-0.301), and water (r=-0.223). Forty-six patients
      (69.7%) had a mean excess energy intake of 384 kcal (SD=630.2), when compared
      with individual nutritional energy estimated requirements. Excess energy intake
      was uncorrelated with age (r=-0.138, P=0.269). Older patients also seem more
      confused with the nutrition information they received (r=0.248) and feel that
      they need more advice on what is a proper diet (r=0.242). Nutrition education
      interventions in this population must be tailored in order to address these
      factors. 

PMID- 26201429
TI  - Good at Heart: Preserving Cardiac Metabolism during aging.
AB  - The natural process of aging determinates several cardiac modifications with
      increased susceptibility to heart diseases and ultimately converging on
      development of chronic heart failure as final stage. These changes mainly include
      left ventricular hypertrophy, diastolic dysfunction, valvular degeneration,
      increased cardiac fibrosis, increased prevalence of atrial fibrillation, and
      decreased maximal exercise capacity, as demonstrated in several humans and animal
      models of aging. While different theories have been proposed to explain the
      natural process of aging, it is clear that most of the alterations affect
      mechanisms involved in cell homeostasis and maintenance. Latest research studies
      have in particular focused on role of mitochondrial oxidative stress, energy
      production and mitochondria quality control. This article reviews the central
      role played by this organelle in aging and the role of new molecular players
      involved into the progression toward heart failure and potentially susceptible of
      new "anti-aging" strategies. 

PMID- 26201430
TI  - Metabolic Syndrome and Aging: Calcium Signaling as Common Regulator.
AB  - Aging is one of the most important societal challenges that western societies
      face, as a result of longer life expectancy and reduced natality rates. Aging is
      a success story of our health and social systems, but raises sustainability
      issues that are linked to the increased need for services of older adults, due to
      the reduction of their independence and to the co-existence of multiple chronic
      diseases. The metabolic syndrome can be considered an age-related disease, since
      its prevalence increases with age. Current demographic trends in the population
      highlight aging-related dysfunctions that contribute to the onset of several
      metabolic diseases, and the need for innovative, effective and sustainable
      approaches. This review describes the correlation between the metabolic syndrome
      and aging, and the underlying common molecular mechanisms, focusing on calcium
      signaling and its crosstalks. 

PMID- 26201432
TI  - Surface functionalization of carbon nanotubes by direct encapsulation with
      varying dosages of amphiphilic block copolymers.
AB  - Encapsulation of carbon nanotubes (CNTs) by amphiphilic block copolymers is an
      efficient way to stabilize CNTs in solvents. However, the appropriate dosages of
      copolymers and the assembled structures are difficult to predict and control
      because of the insufficient understanding on the encapsulation process. We
      encapsulate multiwalled CNTs with polystyrene-block-poly (4-vinyl pyridine) (PS-b
      P4VP) by directly mixing them in acetic acid under sonication. The copolymer
      forms a lamellar structure along the surface of CNTs with the PS blocks anchoring
      on the tube wall and the P4VP blocks exposed to the outside. The encapsulated
      CNTs achieve good dispersibility in polar solvents over long periods. To increase
      our understanding of the encapsulation process we investigate the assembled
      structures and stability of copolymer/CNTs mixtures with changing mass ratios.
      Stable dispersions are obtained at high mass ratios between the copolymer and
      CNTs, i.e. 2 or 3, with the presence of free spherical micelles. Transmission
      electron microscopy and thermal gravimetric analysis determine that the threshold
      for the complete coverage of CNTs by the copolymer occurs at the mass ratio of
      1.5. The coated copolymer layer activates the surface of CNTs, enabling further
      functionalization of CNTs. For instance, atomic layer deposition of TiO(2)
      produces conformal thin layers on the encapsulated CNTs while isolated TiO(2)
      bumps are produced on the pristine, inert CNTs.

PMID- 26201431
TI  - Eco-friendly carbon-nanodot-based fluorescent paints for advanced photocatalytic
      systems.
AB  - Fluorescent carbon nanomaterials, especially zero-dimensional (0D) carbon
      nanodots (CDs), are widely used in broad biological and optoelectronic
      applications. CDs have unique characteristics such as strong fluorescence,
      biocompatibility, sun-light response, and capability of mass-production. Beyond
      the previous green CD obtained from harmful natural substances, we report a new
      type of fluid-based fluorescent CD paints (C-paints) derived from polyethylene
      glycol (PEG; via simple ultrasound irradiation at room temperatures) and produced
      in quantum yields of up to ~14%. Additionally, C-paints possess a strong, UV- and
      visible-light-responsive photoluminescent (PL) property. Most especially, C
      paints, by incorporation into a photocatalytic system, show additional roles in
      the emission of fluorescent light for activation of TiO2 nanoparticles (NPs) and
      the resultant detoxification of most organic dyes, thus further enabling
      embarkation in advanced water purification. 

PMID- 26201433
TI  - Kidney involvement in tuberous sclerosis complex: the impact on healthcare
      resource use and costs.
AB  - OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with non-malignant
      kidney lesions-angiomyolipomata-that may be associated with chronic kidney
      disease (CKD). This study investigated the relationship between renal
      angiomyolipomata and CKD in TSC, including the impact on healthcare resource
      utilization (HCRU) and costs. METHODS: This was a retrospective, longitudinal
      cohort study based on medical record data spanning January 1990-April 2012 for
      369 TSC patients treated at a specialty center in the Netherlands. Cohorts were
      established based on CKD stage and angiomyolipoma size. Rates of HCRU (physician
      visits, monitoring, and interventions) were compared across cohorts using rate
      ratios. Healthcare costs were compared across cohorts using cost differences.
      Regression models were used to identify predictive factors for HCRU and
      healthcare costs. RESULTS: Sixteen per cent of patients reached CKD stage 3 or
      higher during follow-up. Patients at more advanced stages of CKD more frequently
      had either large or multiple small angiomyolipomata and higher HCRU rates and
      healthcare costs. In the multivariate analyses, male gender, CKD stage >1,
      angiomyolipoma size >=3.5 cm, embolization, and the presence of moderate or
      severe lymphangioleiomyomatosis (LAM) were associated with greater HCRU (p <=
      0.002 for all comparisons). Definite (vs suspected) TSC diagnosis, CKD stage 5
      (vs CKD stage 1), angiomyolipoma size >=3.5 cm, and moderate or severe LAM were
      associated with higher costs (p = 0.050 for TSC diagnosis, p <= 0.002 for other
      comparisons). Costs in CKD stage 5 were driven primarily by dialysis.
      CONCLUSIONS: A substantial proportion of patients with TSC developed moderate-to
      severe CKD, which was associated with renal angiomyolipomata and increased HCRU
      and costs.

PMID- 26201434
TI  - Can frequent medical evacuations be reduced by managing chronic disease better in
      the bush?

PMID- 26201435
TI  - Local adaptation at range edges: comparing elevation and latitudinal gradients.
AB  - Local adaptation at range edges influences species' distributions and how they
      respond to environmental change. However, the factors that affect adaptation,
      including gene flow and local selection pressures, are likely to vary across
      different types of range edge. We performed a reciprocal transplant experiment to
      investigate local adaptation in populations of Plantago lanceolata and P. major
      from central locations in their European range and from their latitudinal and
      elevation range edges (in northern Scandinavia and Swiss Alps, respectively). We
      also characterized patterns of genetic diversity and differentiation in
      populations using molecular markers. Range-centre plants of P. major were adapted
      to conditions at the range centre, but performed similarly to range-edge plants
      when grown at the range edges. There was no evidence for local adaptation when
      comparing central and edge populations of P. lanceolata. However, plants of both
      species from high elevation were locally adapted when compared with plants from
      high latitude, although the reverse was not true. This asymmetry was associated
      with greater genetic diversity and less genetic differentiation over the
      elevation gradient than over the latitudinal gradient. Our results suggest that
      adaptation in some range-edge populations could increase their performance
      following climate change. However, responses are likely to differ along elevation
      and latitudinal gradients, with adaptation more likely at high-elevation.
      Furthermore, based upon these results, we suggest that gene flow is unlikely to
      constrain adaptation in range-edge populations of these species.

PMID- 26201437
TI  - Protective tunicate endosymbiont with extreme genome reduction.

PMID- 26201436
TI  - Coping Card Usage can Further Reduce Suicide Reattempt in Suicide Attempter Case
      Management Within 3-Month Intervention.
AB  - This randomized controlled trial was designed to evaluate the effectiveness of
      using crisis coping cards (n = 32) in the case management of suicide prevention
      compared with case management without the use of coping cards (n = 32) over a 3
      month intervention period. The generalized estimating equation was used to
      examine the interaction effect between treatments and time on suicide risk,
      depression, anxiety, and hopelessness. Results indicated that subsequent suicidal
      behaviors, severity of suicide risk, depression, anxiety, and hopelessness were
      reduced more in the coping card intervention group compared to the case
      management only group. Moreover, for the survival curves of time to suicide
      reattempt, the coping card group showed a significantly longer time to reattempt
      than the case management only group at 2-month and 3-month intervention periods.

PMID- 26201438
TI  - Angiographic Evaluation of Coronary Microvascular Dysfunction in Patients with
      Heart Failure and Preserved Ejection Fraction.
AB  - BACKGROUND: The aim of this study was to evaluate myocardial perfusion and
      coronary blood flow through validated angiography indices to assess whether there
      is greater MVD in patients with microvascular angina and HFPEF compared to those
      who do not have. METHODS: Our study was performed on a population of 286 patients
      with stable angina that underwent coronary angiography and echocardiography. They
      showed epicardial coronary arteries free from stenosis. We divided the sample
      into two categories: patients with HFPEF and those without. We calculated indices
      for each patient based on angiographic images, including TFC, MBG, and TMBS.
      RESULTS: Our sample compared two groups: HFPEF (n = 155) and non-HFPEF (n = 135)
      patients. We showed that patients with HFPEF had a longest TFC of three major
      coronary arteries (TFC LAD 44.7 +/- 12.5; TFC RCA 26.2 +/- 6.9; TFC CX 27 +/-
      5.9) than non-HFPEF patients (TFC LAD 40.7 +/- 11.6; TFC RCA 25 +/- 6.3; TFC CX
      21 +/- 4.7). On the other hand, we found lower MBG on three coronary arteries
      (MBG LAD 2.1 +/- 0.3; MBG RCA 2.1 +/- 0.3; MBG CX 2.0 +/- 0.32) in HFPEF than non
      HFPEF patients (MBG LAD 2.6 +/- 0.5; MBG RCA 2.2 +/- 0.47; MBG CX 2.3 +/- 0.4).
      CONCLUSION: Analysis of microcirculation through angiography indices in patients
      with and without HFPEF has led to assess that the HFPEF population has a greater
      involvement of microcirculation than patients without HFPEF.

PMID- 26201439
TI  - A retrospective review of stillbirths at the national hospital in Timor-Leste.
AB  - BACKGROUND: Timor-Leste has high maternal and infant mortality rates. Estimates
      of stillbirths are unreliable and limited by poor collection of vital health
      statistics. Lack of accurate data impedes the development of interventions to
      address local determinants of stillbirth. AIMS: This study aimed to identify the
      rate, timing and causes of stillbirths at National Hospital Guido Valadares in
      Dili, Timor-Leste, between November 2009 and December 2010, during which data
      were available. METHODS: Hospital birth registry and maternal records were
      retrospectively reviewed to identify stillbirths during the study period. The
      simplified Cause of Death and Associated Conditions system was utilised to
      classify stillbirths. RESULTS: One hundred and fifty-three stillbirths were
      identified, producing a stillbirth rate of 29 per 1000 births. Of stillbirths
      with known timing, 70 (66.7%) occurred antepartum and 35 (33.3%) intrapartum.
      Cause of death could not be ascertained in 62.7% of cases due to poor or missing
      records. Where identified, the three most commonly classified causes of death
      were intrapartum fetal asphyxia, maternal infection and maternal hypertensive
      disorder. CONCLUSION: This study highlights the need for standardised recording
      and coding of perinatal deaths at HNGV. The high proportion of antenatal death
      transfers from community health centres demonstrates the need for community and
      hospital staff training to improve the quality of antenatal and intrapartum
      obstetric care. A prospective study of stillbirths is recommended to obtain
      reliable data on the determinants of stillbirths in Timor-Leste. These data would
      inform evidence-based interventions for the improvement of maternity and
      obstetric care in community and hospital settings.

PMID- 26201440
TI  - Repeatability of Retinal Macular Thickness Measurements in Patients with
      Clinically Significant Macular Edema Using Two Different Scanning Protocols of
      Spectralis Optical Coherence Tomography.
AB  - OBJECTIVE: To determine the repeatability of Spectralis optical coherence
      tomography (OCT) retinal thickness measurements in diabetic patients with
      clinically significant macular edema (CSME) using two different scanning
      protocols. METHODS: Seventy-one eyes of 71 diabetic patients with CSME were
      included in the study. Coefficients of repeatability and intrasession variation
      coefficients were tested with 20 * 15 degree raster scans consisting of 19 or 37
      high-resolution line scans (15 or 8 frames per scan, respectively) that were
      repeated 2 times by 1 experienced examiner. The first scan was set as the
      reference scan; the second scan was the follow-up scan and was performed with the
      use of the follow-up mode. RESULTS: The mean and standard deviation for the
      central foveal subfield (CSF) using the first scanning method was 404 +/- 88 MUm,
      while it was 399 +/- 86 MUm using the second protocol, which was not
      statistically significantly different (p = 0.35, paired test). Particularly
      examining the CSF, the coefficient of repeatability was 1.48 (6.00 um) and 1.49
      (5.95 um) for the 19- and the 37-B-scan acquisition, respectively, showing a
      nonstatistically significant difference (p < 0.001). CONCLUSIONS: Retinal
      thickness measurements in diabetic patients with CSME are repeatable using both
      scanning protocols (19 or 37 B-scans) with Spectralis OCT. The repeatability of
      the retinal thickness measurement does not improve by increasing the number of B
      scans from 19 to 37.

PMID- 26201442
TI  - [Health literacy: An introduction to the concept and its measurement].
AB  - Over the last 20 years, health literacy (German: Gesundheitskompetenz/health
      competency) has become a popular concept in research and health policy. Initially
      defined as an individual's ability to understand medical information, the
      definition has quickly expanded to describe individual-based resources for
      actions or conduct relevant to health, in different socio-cultural or clinical
      contexts. Today, researchers and practice experts can draw on a wide variety of
      definitions and measurements. This article provides an overview of the
      definitions, briefly introduces the "structure and agency" approach as an example
      of theorizing health literacy, and shows different types of operationalization.
      The article presents the strengths and shortcomings of the available concepts and
      measures and provides starting points for future research in public health and
      health promotion. 

PMID- 26201441
TI  - RNA binding proteins as regulators of immune cell biology.
AB  - Sequence-specific RNA binding proteins (RBP) are important regulators of the
      immune response. RBP modulate gene expression by regulating splicing,
      polyadenylation, localization, translation and decay of target mRNAs. Increasing
      evidence suggests that RBP play critical roles in the development, activation and
      function of lymphocyte populations in the immune system. This review will discuss
      the post-transcriptional regulation of gene expression by RBP during lymphocyte
      development, with particular focus on the Tristetraprolin family of RBP. 

PMID- 26201443
TI  - Racial Disparities in Seeking Care for Help Getting Pregnant.
AB  - BACKGROUND: Fertility counselling and treatment can help women achieve their
      desired family size; however, disparities exist in the utilisation of this care.
      METHODS: This study examines the persistence of a racial disparity in visiting a
      doctor for help getting pregnant by estimating the direct effect of this
      association using data from the Furthering Understanding of Cancer Health and
      Survivorship in Adult Women's Study, a population-based cohort study. This cohort
      included 1073 reproductive age women (22-45 years) with 28% reporting
      infertility. We fit log binomial models to quantify the magnitude of the racial
      difference in reported care seeking after adjustment for hypothesised mediators
      using inverse probability weighting. RESULTS: Compared with white women, black
      women were less likely to visit a doctor in the total population [adjusted risk
      ratio (RR) 0.57, 95% confidence interval (CI) 0.41, 0.80] and in the subgroup of
      women with infertility [RR 0.75, 95% CI 0.56, 0.99]. In addition, black women
      waited twice as long, on average, before seeking help compared with white women.
      CONCLUSIONS: There were notable racial differences in visiting a doctor for help
      getting pregnant in this study although reports of infertility were similar by
      race. These differences may be mitigated through improved communication about the
      range of counselling and treatment options available.

PMID- 26201444
TI  - Diabetes and obesity trends in Fiji over 30 years.
AB  - BACKGROUND: No systematic comparison has been conducted in Fiji using all
      suitable surveys of type 2 diabetes mellitus (T2DM) and obesity prevalence after
      standardizing methodology and definitions. METHODS: Unit records from six surveys
      of Fiji adults were variously adjusted for age, ethnicity (Fiji Melanesians, i
      Taukei, and Fijians of Asian Indian descent [Indians]) and urban-rural by sex to
      previous censuses. Trends were assessed using meta-regression (random effect
      models) and estimates projected to 2020. Poisson regression of strata was used to
      assess the effect of body mass index (BMI) increases on T2DM period trends.
      RESULTS: Over 1980-2011, T2DM prevalence increased in i-Taukei men (3.2% to
      11.1%; 1.32%/5 years) and women (5.3% to 13.6%; 1.40%/5 years) and Indian men
      (11.1% to 17.9%; 1.24%/5 years) and women (11.2% to 19.9%; 1.71%/5 years).
      Projected T2DM prevalence in 2020 is 13.3% and 16.7% in i-Taukei men and women,
      and 23.4% and 24.1% in Indian men and women, respectively. Obesity prevalence
      increased in i-Taukei men (12.6% to 28.9%; 2.99%/5 years) and women (30.1% to
      52.9%; 3.84%/5 years) and in Indian men (2.8% to 9.4%; 1.21%/5 years) and women
      (13.2% to 26.6%; 2.61%/5 years). Projected obesity prevalence in 2020 is 34.0%
      and 60.0% in i-Taukei and women, and 11.4% and 31.0% in Indian men and women,
      respectively. After age-adjustment, an estimated 27%, 25%, 16% and 18% of the
      T2DM period trend is attributable to BMI in i-Taukei men and women and Indian men
      and women, respectively. CONCLUSIONS: Prevalence of T2DM in Fiji is projected to
      continue increasing, driven by rising obesity, with consequences for premature
      mortality and life expectancy.

PMID- 26201445
TI  - Small Dielectric Spheres with High Refractive Index as New Multifunctional
      Elements for Optical Devices.
AB  - The future of ultra-fast optical communication systems is inevitably connected
      with progress in optical circuits and nanoantennas. One of the key points of this
      progress is the creation of elementary components of optical devices with
      scattering diagrams tailored for redirecting the incident light in a desired
      manner. Here we demonstrate theoretically and experimentally that a small,
      simple, spatially homogeneous dielectric subwavelength sphere with a high
      refractive index and low losses (as some semiconductors in the visible or near
      infrared region) exhibits properties allowing to utilize it as a new
      multifunctional element for the mentioned devices. This can be achieved by taking
      advantage of the coherent effects between dipolar and multipolar modes, which
      produce anomalous scattering effects. The effects open a new way to control the
      directionality of the scattered light. The directional tuning can be obtained in
      a practical way just by a change in the frequency of the incident wave, and/or by
      a well-chosen diameter of the sphere. Dielectric nanoparticles with the required
      optical properties in the VIS-NIR may be now readily fabricated. These particles
      could be an efficient alternative to the widely discussed scattering units with a
      more complicated design. 

PMID- 26201447
TI  - In vitro postantifungal effect, adhesion traits and haemolysin production of
      Candida dubliniensis isolates following exposure to 5-fluorocytosine.
AB  - The phenomenon of postantifungal effect (PAFE), which is the suppression of
      candidal growth following brief exposure to antifungal agents, is linked with
      candidal pathogenicity. Adhesion to buccal epithelial cells (BEC), germ tube (GT)
      formation and relative cell surface hydrophobicity (CSH) are all adhesion traits
      of candidal pathogenicity. Ability to produce haemolysin by Candida species is
      also a determinant of its pathogenicity. There is no information on either the
      PAFE or its impact on adhesion traits and haemolysin production of oral Candida
      dubliniensis isolates following exposure to 5-fluorocytosine (5-FC). Hence, the
      focus of this investigation was to research the in vitro PAFE, adhesion to BEC,
      GT formation, relative CSH and haemolysin production on 20 C. dubliniensis
      isolates following exposure to 5-FC. Following obtaining the minimum inhibitory
      concentration (MIC) of 5-FC, isolates of C. dubliniensis were exposed to sub
      lethal concentrations (*3 MIC) of 5-FC for 1 h. After this brief exposure, the
      antimycotic was removed and PAFE, adhesion to BEC, GT formation, relative CSH and
      haemolysin production was determined by formerly described in vitro methods. MIC
      (MUg/ml) of C. dubliniensis isolates to 5-FC ranged from 0.002 to 0.125. The mean
      PAFE (hours) elicited by 5-FC on C. dubliniensis isolates was approximately 1 h.
      Exposure to 5-FC suppressed the ability of C. dubliniensis isolates to adhere
      BEC, GT formation, relative CSH and haemolysin activity by a mean percentage
      reduction in 50.98%, 29.51%, 36.79% and 12.75% (P < 0.001 for all) respectively.
      Therefore, brief exposure of C. dubliniensis isolates to 5-FC appears to exert an
      antifungal effect by subduing its growth, adhesion traits as well as haemolysin
      production.

PMID- 26201446
TI  - miR-504 mediated down-regulation of nuclear respiratory factor 1 leads to radio
      resistance in nasopharyngeal carcinoma.
AB  - microRNAs (miRNAs) are involved in the various processes of DNA damage repair and
      play crucial roles in regulating response of tumors to radiation therapy. Here,
      we used nasopharyngeal carcinoma (NPC) radio-resistant cell lines as models and
      found that the expression of miR-504 was significantly up-regulated. In contrast,
      the expression of nuclear respiratory factor 1 (NRF1) and other mitochondrial
      metabolism factors, including mitochondrial transcription factor A (TFAM) and
      oxidative phosphorylation (OXPHOS) complex III were down-regulated in these cell
      lines. At the same time, the Seahorse cell mitochondrial stress test results
      indicated that the mitochondrial respiratory capacity was impaired in NPC radio
      resistant cell lines and in a miR-504 over-expressing cell line. We also
      conducted dual luciferase reporter assays and verified that miR-504 could
      directly target NRF1. Additionally, miR-504 could down-regulate the expression of
      TFAM and OXPHOS complexes I, III, and IV and impaired the mitochondrial
      respiratory function of NPC cells. Furthermore, serum from NPC patients showed
      that miR-504 was up-regulated during different weeks of radiotherapy and
      correlated with tumor, lymph nodes and metastasis (TNM) stages and total tumor
      volume. The radio-therapeutic effect at three months after radiotherapy was
      evaluated. Results indicated that patients with high expression of miR-504
      exhibited a relatively lower therapeutic effect ratio of complete response (CR),
      but a higher ratio of partial response (PR), compared to patients with low
      expression of miR-504. Taken together, these results demonstrated that miR-504
      affected the radio-resistance of NPC by down-regulating the expression of NRF1
      and disturbing mitochondrial respiratory function. Thus, miR-504 might become a
      promising biomarker of NPC radio-resistance and targeting miR-504 might improve
      tumor radiation response.

PMID- 26201448
TI  - miR-221/222 Are Involved in Response to Sunitinib Treatment in Metastatic Renal
      Cell Carcinoma.
AB  - Sunitinib is a multitargeting tyrosine kinase inhibitor used for metastatic renal
      cancer. There are no biomarkers that can predict sunitinib response. Such markers
      are needed to avoid administration of costly medication with side effects to
      patients who would not benefit from it. We compared global miRNA expression
      between patients with a short (<=12 months) versus prolonged (>12 months)
      progression-free survival (PFS) under sunitinib as first-line therapy for
      metastatic renal cell carcinoma. We identified a number of differentially
      expressed miRNAs and developed miRNA statistical models that can accurately
      distinguish between the two groups. We validated our models in the discovery set
      and an independent set of 57 patients. Target prediction and pathway analysis
      showed that these miRNAs are involved in vascular endothelial growth factor
      (VEGF), TGFbeta, and mammalian target of rapamycin (mTOR)-mediated signaling and
      cell-cell communication. We tested the effect of these miRNAs on cellular
      proliferation and angiogenesis. We validated the negative correlation between miR
      221 and its target, VEGFR2.miR-221 overexpression was associated with a poor PFS
      while its target, VEGFR2 was associated with longer survival. Gain of function
      experiments showed that miR-221 and miR-222 decreased angiogenesis and cellular
      proliferation in human umbilical vein endothelial cells (HUVEC) while increasing
      cellular proliferation in ACHN cells. miRNAs represent potential predictive
      markers for sunitinib response. 

PMID- 26201450
TI  - Pulmonary embolism after blood donation in a healthy young female.

PMID- 26201449
TI  - Huntingtin Haplotypes Provide Prioritized Target Panels for Allele-specific
      Silencing in Huntington Disease Patients of European Ancestry.
AB  - Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG
      repeat expansion in the Huntingtin gene (HTT). Heterozygous polymorphisms in cis
      with the mutation allow for allele-specific suppression of the pathogenic HTT
      transcript as a therapeutic strategy. To prioritize target selection, precise
      heterozygosity estimates are needed across diverse HD patient populations. Here
      we present the first comprehensive investigation of all common target alleles
      across the HTT gene, using 738 reference haplotypes from the 1000 Genomes Project
      and 2364 haplotypes from HD patients and relatives in Canada, Sweden, France, and
      Italy. The most common HD haplotypes (A1, A2, and A3a) define mutually exclusive
      sets of polymorphisms for allele-specific therapy in the greatest number of
      patients. Across all four populations, a maximum of 80% are treatable using these
      three target haplotypes. We identify a novel deletion found exclusively on the A1
      haplotype, enabling potent and selective silencing of mutant HTT in approximately
      40% of the patients. Antisense oligonucleotides complementary to the deletion
      reduce mutant A1 HTT mRNA by 78% in patient cells while sparing wild-type HTT
      expression. By suppressing specific haplotypes on which expanded CAG occurs, we
      demonstrate a rational approach to the development of allele-specific therapy for
      a monogenic disorder. 

PMID- 26201451
TI  - Localization-based full-field microscopy: how to attain super-resolved images.
AB  - In this study, we have investigated localization-based microscopy to achieve full
      field super-resolution. For localized sampling, we have considered combs
      consisting of unit pulses and near-fields localized by surface nanoapertures.
      Achievable images after reconstruction were assessed in terms of peak signal-to
      noise ratio (PSNR). It was found that spatial switching of individual pulses may
      be needed to break the diffraction limit. Among the parameters, the resolution
      was largely determined by sampling period while the effect of width of a sampling
      pulse on PSNR was relatively limited. For the range of sampling parameters that
      we considered, the highest resolution achievable is estimated to be 70 nm, which
      can further be enhanced by optimizing the localization parameters. 

PMID- 26201452
TI  - Contribution of treatment acceptability to acceptance of randomization: an
      exploration.
AB  - RATIONALE, AIMS AND OBJECTIVES: Randomization to treatment is viewed unfavourably
      by many trial participants. There is limited research that investigated factors
      contributing to acceptance of randomization. This study explored the influence of
      participants' socio-demographic and clinical characteristics, and their perceived
      acceptability of the treatments on their acceptance of randomization (i.e.
      willingness to be randomized) in a clinical trial. METHODS: Persons with insomnia
      (n = 383) were asked about their acceptance of randomization before and after
      they rated the acceptability of behavioural therapies for managing insomnia
      (sleep education and hygiene booklet, stimulus control therapy and sleep
      restriction therapy). Socio-demographic and clinical characteristics, and
      treatment acceptability, were measured with established instruments. Logistic
      regression was applied to explore the association between participants'
      characteristics and treatment acceptability, and reported acceptance of
      randomization. RESULTS: Prior to rating treatments' acceptability, 54.6% of
      participants were willing to be randomized; socio-demographic (age and ethnicity)
      and clinical (severity of insomnia's impact, state anxiety, depression, vitality
      and mental and social functions) contributed to acceptance of randomization.
      After rating the treatments' acceptability, 87.8% of participants were unwilling
      to be randomized; age, severity of insomnia's impact and acceptability of
      behavioural therapy were significantly associated with acceptance of
      randomization. CONCLUSIONS: The study findings indicated that participants are
      likely to express unwillingness to be randomized once they receive treatment
      information and rate the acceptability of treatments. The reported non-acceptance
      may influence participants' behaviour (e.g. withdrawal, non-adherence) during the
      trial, suggesting the need to explore alternative designs for intervention
      evaluation.

PMID- 26201454
TI  - Idiopathic Intracranial Hypertension in the Northwest of Northern Ireland:
      Epidemiology and Clinical Management.
AB  - BACKGROUND: There is limited literature on the epidemiology of idiopathic
      intracranial hypertension (IIH). The diagnosis and management of IIH require a
      multidisciplinary approach. We sought to study the incidence as well as
      prevalence of IIH and to evaluate the current management of IIH in the northwest
      of Northern Ireland. METHODS: Medical records of patients diagnosed with IIH
      between 2007 and 2014 in a general hospital in Northern Ireland were reviewed.
      Clinical and outcome data were retrieved. RESULTS: There were 45 patients with
      IIH, 44 women: 1 man. The mean age at presentation was 29.4 (SD 9.8) years and
      mean body mass index (BMI) 39.8 (SD 9.5) kg/ m(2). All patients had neuroimaging,
      44 (98%) had CT/MR venogram and 41 (91%) had visual perimetry. The crude
      incidence of IIH was 2.36 per 100,000 (95% CI 1.65-3.37). For women, the
      incidence was 4.65 per 100,000/year (95% CI 3.25-6.66). The prevalence was 14.3
      per 100,000 overall (95% CI 9.72-20.9) but 28.1 per 100,000 in women (95% CI 19.2
      41.2). Visual field defects were identified in 25 of 41 (61%); 4 patients (9%)
      required shunting procedures. At follow-up, the mean BMI decreased by 1.6 kg/m(2)
      (p = 0.024). CONCLUSIONS: The incidence of IIH in the northwest of Northern
      Ireland is among the highest ever reported and probably reflects the known
      increase in obesity.

PMID- 26201453
TI  - Renal function and long-term decline in cognitive function: the Baltimore
      Longitudinal Study of Aging.
AB  - BACKGROUND: Renal disease has been associated with greater risk of dementia and
      greater cognitive impairment. However, the relationship of lower renal function
      with long-term decline in specific domains of cognitive function remains unclear
      among community-dwelling, non-demented individuals. METHODS: Stroke- and dementia
      free participants (n = 2,116) were enrolled in the Baltimore Longitudinal Study
      of Aging, a community-based, prospective, longitudinal study. Renal function was
      estimated by the inverse of serum creatinine adjusted for age, sex and race and
      (in sensitivity analyses) estimated glomerular filtration rate (eGFR) using the
      MDRD formula. Outcome measures were changes in scores on 6 cognitive tests
      encompassing a range of cognitive functions, measured at 2-year intervals. Mixed
      effects regression models examined the longitudinal relations of renal function
      with cognitive functions after adjusting for demographics, comorbidity and other
      potential confounders. RESULTS: Mean age at initial testing was 53.9 years (SD
      17.1), and 94 participants (4.4%) had an eGFR <60 ml/min/1.73 m(2) and 18.5% had
      at least one comorbidity. With increasing age, longitudinal increases in
      creatinine concentrations were associated with more rapid decline in performance
      on several cognitive measures, including the learning slope of the California
      Verbal Learning Test, a test of verbal learning (p < 0.01), and the Benton Visual
      Retention Test, a test of visual memory (p < 0.01). Associations were similar for
      changes in eGFRMDRD, which was also associated with the rate of decline in verbal
      memory. CONCLUSION: In a community-based adult population, declines in renal
      function independently associated with greater long-term declines in visual
      memory and verbal memory and learning.

PMID- 26201455
TI  - PRGF exerts a cytoprotective role in zoledronic acid-treated oral cells.
AB  - OBJECTIVES: Bisphosphonates-related osteonecrosis of the jaw (BRONJ) is a common
      problem in patients undergoing long-term administration of highly potent nitrogen
      containing bisphosphonates (N-BPs). This pathology occurs via bone and soft
      tissue mechanism. Zoledronic acid (ZA) is the most potent intravenous N-BP used
      to prevent bone loss in patients with bone dysfunction. The objective of this in
      vitro study was to evaluate the role of different ZA concentrations on the cells
      from human oral cavity, as well as the potential of plasma rich in growth factors
      (PRGF) to overcome the negative effects of this BP. MATERIAL AND METHODS: Primary
      human gingival fibroblasts and primary human alveolar osteoblasts were used. Cell
      proliferation was evaluated by means of a fluorescence-based method. A
      colorimetric assay to detect DNA fragmentation undergoing apoptosis was used to
      determine cell death, and the expression of both NF-kappaB and pNF-kappaB were
      quantified by Western blot analysis. RESULTS: ZA had a cytotoxic effect on both
      human gingival fibroblasts and human alveolar osteoblasts. This BP inhibits cell
      proliferation, stimulates apoptosis, and induces inflammation. However, the
      addition of PRGF suppresses all these negative effects of the ZA. CONCLUSIONS:
      PRGF shows a cytoprotective role against the negative effects of ZA on primary
      oral cells. CLINICAL RELEVANCE: At present, there is no definitive treatment for
      bisphosphonates-related osteonecrosis of the jaw (BRONJ), being mainly
      palliatives. Our results revealed that PRGF has a cytoprotective role in cells
      exposed to zoledronic acid, thus providing a reliable adjunctive therapy for the
      treatment of BRONJ pathology.

PMID- 26201456
TI  - Trait body shame predicts health outcomes in college women: A longitudinal
      investigation.
AB  - Trait body shame impacts psychological health, but its influence on physical
      health heretofore has not been examined. While body shame may be expected to
      impact physical health through many mechanisms, this investigation tested whether
      trait body shame predicts physical health outcomes by promoting negative
      attitudes toward bodily processes, thereby diminishing health evaluation and
      ultimately impacting physical health. Correlational (Study 1, N = 177) and
      longitudinal (Study 2, N = 141) studies tested hypotheses that trait body shame
      would predict infections, self-rated health, and symptoms, and that body
      responsiveness and health evaluation would mediate these relationships. In Study
      1, trait body shame predicted all three poor health outcomes, and body
      responsiveness and health evaluation mediated these relationships. Study 2
      partially replicated these results while controlling for depression, smoking, and
      BMI, and longitudinal analyses supported the temporal precedence of trait body
      shame in the proposed model. Limitations and alternative pathways are discussed.

PMID- 26201457
TI  - Evidence for anti-apoptotic roles of proteasome activator 28gamma via inhibiting
      caspase activity.
AB  - Proteasome activator PA28gamma (REGgamma, Ki antigen) has recently been
      demonstrated to display anti-apoptotic properties via enhancing Mdm2-p53
      interaction, thereby facilitating ubiquitination and down-regulation of the tumor
      suppressor p53. In this study we demonstrate a correlation between cellular
      PA28gamma levels and the sensitivity of cells towards apoptosis in different
      cellular contexts thereby confirming a role of proteasome activator PA28gamma as
      an anti-apoptotic regulator. We investigated the anti-apoptotic role of PA28gamma
      upon UV-C stimulation in B8 mouse fibroblasts stably overexpressing the PA28gamma
      encoding PSME3 gene and upon butyrate-induced apoptosis in human HT29
      adenocarcinoma cells with silenced PSME3 gene. Interestingly, our results
      demonstrate that PA28gamma has a strong influence on different apoptotic
      hallmarks, especially p53 phosphorylation and caspase activation. In detail,
      PA28gamma and effector caspases mutually restrict each other. PA28gamma is a
      caspase substrate, if PA28gamma levels are low. In contrast, PA28gamma
      overexpression reduces caspase activities, including the caspase-dependent
      processing of PA28gamma. Furthermore, overexpression of PA28gamma resulted in a
      nuclear accumulation of transcriptional active p53. In summary, our findings
      indicate that even in a p53-dominated cellular context, pro-apoptotic signaling
      might be overcome by PA28gamma-mediated caspase inhibition. 

PMID- 26201458
TI  - The miR-573/apoM/Bcl2A1-dependent signal transduction pathway is essential for
      hepatocyte apoptosis and hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with an
      increasing incidence worldwide. Apolipoprotein M (apoM) is a novel apolipoprotein
      that is mainly expressed in liver and kidney tissues. However, the anti-tumor
      properties of apoM remain largely unknown. We evaluated the anti-tumor activities
      and mechanisms of apoM in HCC both in vivo and in vitro. Bioinformatic analysis
      and luciferase reporter assay results showed that apoM was a potential target of
      hsa-miR-573 and was downregulated after transfection with hsa-miR-573 mimics.
      Overexpression of apoM suppressed migration, invasion, and proliferation of
      hepatoma cells in vitro. Overexpression of hsa-miR-573 in hepatoma cells reduced
      apoM expression, leading to promotion of the invasion, migration, and
      proliferation of hepatoma cells in vitro. In addition, hsa-miR-573 markedly
      promoted growth of xenograft tumors in nude mice with an accompanying reduction
      in cell apoptosis. ApoM markedly inhibited growth of xenograft tumors in nude
      mice and promoted cell apoptosis. Moreover, Bcl2A1 mRNA and protein levels were
      inhibited by apoM overexpression and an increase in apoptosis rate by apoM was
      markedly compensated by Bcl2A1 overexpression in HepG2 cells. These results
      provide evidence that hsa-miR-573 promoted tumor growth by inhibition of
      hepatocyte apoptosis and this pro-tumor effect might be mediated through Bcl2A1
      in an apoM-dependent manner. Therefore, our findings may be useful to improve
      understanding of the critical effects of hsa-miR-573 and apoM in HCC
      pathogenesis. 

PMID- 26201459
TI  - Necrotizing pneumonia due to clonally diverse Staphylococcus aureus strains
      producing Panton-Valentine leukocidin: the Czech experience.
AB  - A prospective study (2007-2013) was undertaken to investigate clinical features
      and prognostic factors of necrotizing pneumonia caused by Staphylococcus aureus
      producing Panton-Valentine leukocidin (PVL) in the Czech Republic. Twelve cases
      of necrotizing pneumonia were detected in 12 patients (median age 25 years)
      without severe underlying disease. Eight cases occurred in December and January
      and the accumulation of cases in the winter months preceding the influenza season
      was statistically significant (P < 0.001). The course of pneumonia was very
      rapid, leading to early sepsis and/or septic shock in all but one patient. Seven
      patients died and mortality was fourfold higher in those patients presenting with
      primary pneumonia than with pneumonia complicating other staphylococcal/pyogenic
      infection elsewhere in the body. The S. aureus isolates displayed considerable
      genetic variability and were assigned to five lineages CC8 (n = 3), CC15 (n = 2),
      CC30 (n = 2), CC80 (n = 1), and CC121 (n = 3) and one was a singleton of ST154 (n
      = 1), all were reported to be associated with community-acquired infection. Four
      strains were methicillin resistant. The high case-fatality rate can only be
      reduced by improving the speed of diagnosis and a rapid test to detect S. aureus
      in the airways is needed. 

PMID- 26201460
TI  - [Delayed treatment initiation of more than 2 weeks. Relevance for possible gain
      of visual acuity after anti-VEGF therapy under real life conditions (interim
      analysis of the prospective OCEAN study)].
AB  - BACKGROUND: The largest German prospective non-interventional ophthalmological
      study OCEAN (NCT02194803) investigates the treatment of retinal diseases with
      ranibizumab in routine patient care. A feature of this study is the participation
      of ophthalmic surgeons in surgical centers as well as general ophthalmologists
      who do not perform intravitreal injections themselves. OBJECTIVES: The functional
      outcome following administration of three intravitreal injections was analyzed
      with respect to the time from initial examination to the first injection (defined
      as treatment delay) as well as potentially confounding factors. MATERIAL AND
      METHODS: This interim analysis included only data from therapy naive patients
      participating in the OCEAN study, who received at least three ranibizumab
      injections. The potential impact of various factors on treatment delay was
      analyzed by the chi(2)-test. RESULTS: Data of 1333 patients were analyzed. The
      median delay before treatment was 15 days (range 0-90 days). Patients with a
      delay of more than 28 days showed a significantly lower gain in visual acuity
      than patients with a delay of less than 14 days. Age, gender and baseline visual
      acuity did not show an association with the treatment delay; however, referral
      from a primary care ophthalmologist, undertaking fluorescein angiography in an
      external practice and the underlying indications did affect the observed
      treatment delays. CONCLUSION: Every patient should be treated within 14 days,
      following recent recommendations of the ophthalmological societies. Liability
      issues have to be considered as the statistical evaluation of real life data
      showed unambiguous results.

PMID- 26201462
TI  - Collagenase Clostridium Histolyticum: A Review in Peyronie's Disease.
AB  - Collagenase Clostridium Histolyticum (CCH) (Xiaflex((r)), Xiapex((r)))
      intralesional injection is a mixture of class I (AUX-I) and class II (AUX-II)
      clostridial collagenases. It is indicated for the treatment of adult men with
      Peyronie's disease with a palpable plaque and curvature deformity of >= 30
      degrees  at the start of therapy. This article reviews the efficacy and
      tolerability of CCH in this indication and briefly summarizes its pharmacology.
      CCH treatment significantly improved penile curvature deformity and reduced
      patient-reported bother associated with Peyronie's disease in the 52-week, double
      blind, phase III IMPRESS I and II studies. Treatment benefit with CCH was also
      seen in 36-week, open-label studies, providing further support for its efficacy.
      CCH was generally well tolerated in patients with Peyronie's disease, with most
      treatment-related adverse events being of mild or moderate severity. Serious
      treatment-related adverse events (penile haematoma or corporal ruptures) were
      reported in <1% of CCH recipients in clinical studies. Although further studies
      assessing the long-term effects of CCH intralesional injection are needed,
      current evidence indicates that this is a minimally invasive, effective and
      generally well tolerated treatment option for patients with Peyronie's disease.

PMID- 26201463
TI  - Cangrelor: A Review in Percutaneous Coronary Intervention.
AB  - Cangrelor (Kengrexal((r)), Kengreal(TM)) is an intravenously administered P2Y12
      receptor inhibitor. It is direct-acting and reversible, with a very rapid onset
      and offset of action. The randomized, double-blind, multinational, phase III
      CHAMPION PHOENIX trial compared the efficacy of intravenous cangrelor with that
      of oral clopidogrel in patients requiring percutaneous coronary intervention
      (PCI) for stable angina pectoris, a non-ST-segment elevation acute coronary
      syndrome or ST-segment elevation myocardial infarction (MI). The primary
      composite efficacy endpoint of death from any cause, MI, ischaemia-drive
      revascularization or stent thrombosis in the 48 h following randomization
      occurred in significantly fewer cangrelor than clopidogrel recipients. The rate
      of severe or life-threatening non-coronary artery bypass graft-related, GUSTO
      defined bleeding at 48 h did not significantly differ between cangrelor and
      clopidogrel recipients. In conclusion, intravenous cangrelor is an important new
      option for use in patients undergoing PCI who have not been treated with oral
      P2Y12 inhibitors.

PMID- 26201461
TI  - Non-Alcoholic Steatohepatitis: Limited Available Treatment Options but Promising
      Drugs in Development and Recent Progress Towards a Regulatory Approval Pathway.
AB  - The prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic
      steatohepatitis (NASH) is increasing world-wide in parallel to the increase of
      the obesity epidemic. Insulin resistance (IR) and the accumulation of
      triglyceride-derived toxic lipid metabolites play a key role in its pathogenesis.
      Multiple biomarkers are being evaluated for the non-invasive diagnosis of NASH.
      However, a percutaneous liver biopsy is still the gold standard method; the
      minimal diagnostic criteria include the presence of >5% macrovesicular steatosis,
      inflammation, and liver cell ballooning. Several pharmaceutical agents have been
      evaluated for the treatment of NASH; however, no single therapy has been approved
      so far. Due to the increasing prevalence and the health burden, there is a high
      need to develop therapeutic strategies for patients with NASH targeting both
      those with early-stage disease as well as those with advanced liver fibrosis.
      There are unique challenges in the design of studies for these target
      populations. Collaborative efforts of health authorities, medical disease
      experts, and the pharmaceutical industry are ongoing to align options for a
      registrational pathway. Several companies pursuing different mechanisms of action
      are nearing the end of phase II with their candidates. This manuscript reviews
      those compounds with a variety of mode of actions that have been evaluated and/or
      are currently being tested with the goal of achieving a NAFLD/NASH indication.

PMID- 26201464
TI  - Intracranial abscess due to Mycobacterium avium complex in an immunocompetent
      host: a case report.
AB  - BACKGROUND: Mycobacterium avium complex (MAC) is a ubiquitous pathogen, widely
      distributed in the environment including water, soil and animals. It is an
      uncommonly encountered clinical pathogen; primarily causing pulmonary infections
      in patients with underlying lung disease or disseminated disease in
      immunocompromised hosts. Sporadically, extra-pulmonary infections have been
      documented including involvement of the liver, spleen, skin, soft tissue and
      lymph nodes. Central nervous system (CNS) infections due to MAC are exceedingly
      rare and carry a poor prognosis. Additionally, such infections are largely
      reported in patients infected with HIV. Herein we report the first case of
      intracranial abscess due to MAC in an immunocompetent man with a normal CD4 count
      and negative HIV status. CASE PRESENTATION: A previously healthy 40-year-old male
      presented to us with progressively worsening CNS symptoms. The patient's
      presentation was uncharacteristic of MAC infection in immunocompetent hosts, as
      he developed subacute, progressive symptoms that included severe frontal
      headaches, left eyelid swelling, blurry vision, and diplopia, without any
      pulmonary or systemic manifestations. Neuroimaging revealed multiple ring
      enhancing lesions, which required neurosurgical intervention. MAC was the only
      pathogen that grew from intraoperative tissue cultures. The patient was
      subsequently treated with a 12-month regimen consisting of Clarithromycin,
      Ethambutol, and Rifampin, with successful clinical resolution. CONCLUSION: Our
      findings indicate that it is important to consider rare infections such as MAC in
      immunocompetent patients, regardless of atypical symptoms. Despite the severity
      of this infection, with timely diagnosis effective treatment is available.

PMID- 26201465
TI  - Flexible ureteroscopy training for surgeons using isolated porcine kidneys in
      vitro.
AB  - BACKGROUND: To evaluate the feasibility of flexible ureteroscopy training by
      using isolated porcine kidneys and ureters in vitro. METHODS: Twenty young
      urologists were randomly divided into four groups. Overall performance was
      assessed based on a global rating scale, pass/fail rating, total time to complete
      task, learning curve, incidence of trauma, and perforations. The effect of
      training was determined by comparing their performance in baseline with that in
      the post-test. RESULTS: After the training, average operation time significantly
      decreased from 18 +/- 3.4 min to 11 +/- 1.2 min (P < 0.05). The urologists
      exhibited a relatively stable performance level after the sixth operation.
      Significant differences were observed between pre-test and post-test with respect
      to the global rating scale and the pass/fail rating (P < 0.05). However, the
      incidence of mucosal trauma and perforations did not change significantly (P =
      0.26 and 0.35, respectively). CONCLUSIONS: The isolated porcine kidneys are
      convenient and intuitive models for young urologists to practice flexible
      ureteroscopy on.

PMID- 26201467
TI  - Parents' experiences of caring for a young person with neurofibromatosis type 1
      (NF1): a qualitative study.
AB  - Neurofibromatosis type 1 (NF1) is a variable and unpredictable genetic condition
      that can lead to changes to an individual's appearance. Research has started to
      explore children's and young people's experiences of living with the condition;
      however, there is a lack of research with parents. This exploratory qualitative
      study set out to examine parents' experiences of caring for a young person with
      NF1. Seven parents took part in semi structured interviews which were subjected
      to a thematic analysis. Three key themes were identified which related to
      managing the uncertainty of the condition, the impact of an altered appearance,
      and others' awareness and understanding of NF1. Parents felt that understanding
      NF1 themselves in order to support their child was beneficial whilst a perceived
      lack of understanding by others was cited as a significant challenge. Parents
      require trustworthy information and also more widely call for greater
      understanding and awareness of the condition. 

PMID- 26201466
TI  - Kiwi genome provides insights into evolution of a nocturnal lifestyle.
AB  - BACKGROUND: Kiwi, comprising five species from the genus Apteryx, are endangered,
      ground-dwelling bird species endemic to New Zealand. They are the smallest and
      only nocturnal representatives of the ratites. The timing of kiwi adaptation to a
      nocturnal niche and the genomic innovations, which shaped sensory systems and
      morphology to allow this adaptation, are not yet fully understood. RESULTS: We
      sequenced and assembled the brown kiwi genome to 150-fold coverage and annotated
      the genome using kiwi transcript data and non-redundant protein information from
      multiple bird species. We identified evolutionary sequence changes that underlie
      adaptation to nocturnality and estimated the onset time of these adaptations.
      Several opsin genes involved in color vision are inactivated in the kiwi. We date
      this inactivation to the Oligocene epoch, likely after the arrival of the
      ancestor of modern kiwi in New Zealand. Genome comparisons between kiwi and
      representatives of ratites, Galloanserae, and Neoaves, including nocturnal and
      song birds, show diversification of kiwi's odorant receptors repertoire, which
      may reflect an increased reliance on olfaction rather than sight during foraging.
      Further, there is an enrichment of genes influencing mitochondrial function and
      energy expenditure among genes that are rapidly evolving specifically on the kiwi
      branch, which may also be linked to its nocturnal lifestyle. CONCLUSIONS: The
      genomic changes in kiwi vision and olfaction are consistent with changes that are
      hypothesized to occur during adaptation to nocturnal lifestyle in mammals. The
      kiwi genome provides a valuable genomic resource for future genome-wide
      comparative analyses to other extinct and extant diurnal ratites.

PMID- 26201468
TI  - Targeting the heparin-binding domain of fibroblast growth factor receptor 1 as a
      potential cancer therapy.
AB  - BACKGROUND: Aberrant activation of fibroblast growth factor receptors (FGFRs)
      deregulates cell proliferation and promotes cell survival, and may predispose to
      tumorigenesis. Therefore, selective inactivation of FGFRs is an important
      strategy for cancer therapy. Here as a proof-of-concept study, we developed a
      FGFR1 neutralizing antisera, IMB-R1, employing a novel strategy aimed at
      preventing the access of essential heparan sulfate (HS) co-receptors to the
      heparin-binding domain on FGFR1. METHODS: The mRNA and protein expression level
      of FGFR1 and other FGFRs were examined in several lines of breast cancer and
      osteosarcoma cells and corresponding normal cells using Taqman real-time
      quantitative PCR and Western blot analysis. The specificity of IMB-R1 against
      FGFR1 was assessed with various ELISA-based approaches and Receptor Tyrosine
      Kinase array. Proliferation assay and apoptosis analysis were performed to assess
      the effect of IMB-R1 on cancer cell growth and apoptosis, respectively, in
      comparison with known FGFR1 inhibitors. The IMB-R1 induced alteration of
      intracellular signaling and gene expression were analysed using Western blot and
      microarray approaches. Immunohistochemical staining of FGFR1 using IMB-R1 were
      carried out in different cancer tissues from clinical patients. Throughout the
      study, statistical differences were determined by Student's t test where
      appropriate and reported when a p value was less than 0.05. RESULTS: We
      demonstrate that IMB-R1 is minimally cross-reactive for other FGFRs, and that it
      potently and specifically inhibits binding of heparin to FGFR1. Furthermore, IMB
      R1 blocks the interaction of FGF2 with FGFR1, the kinase activity of FGFR1 and
      activation of intracellular FGFR signaling. Cancer cells treated with IMB-R1
      displayed impaired FGF2 signaling, were unable to grow and instead underwent
      apoptosis. IMB-R1-induced cell death correlated with a disruption of
      antioxidative defense networks and increased expression of several tumor
      suppressors and apoptotic proteins, including p53. Immunostaining with IMB-R1 was
      stronger in human cancer tissues in which the FGFR1 gene is amplified.
      CONCLUSION: Our study suggests that blocking HS interaction with the heparin
      binding domains of FGFR1 inhibited cancer cell growth, which can be an attractive
      strategy to inactivate cancer-related heparin-binding proteins.

PMID- 26201470
TI  - Liver transplantation for hepatocellular carcinoma: how far can the selection
      criteria be expanded?

PMID- 26201469
TI  - Asian-Pacific consensus statement on the management of chronic hepatitis B: a
      2012 update.
AB  - Large volume of new data on the natural history and treatment of chronic
      hepatitis B virus (HBV) infection have become available since 2008. These include
      further studies in asymptomatic subjects with chronic HBV infection and community
      based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the
      application of non-invasive assessment of hepatic fibrosis and quantitation of
      HBV surface antigen and new drug or new strategies towards more effective
      therapy. To update HBV management guidelines, relevant new data were reviewed and
      assessed by experts from the region, and the significance of the reported
      findings was discussed and debated. The earlier "Asian-Pacific consensus
      statement on the management of chronic hepatitis B" was revised accordingly. The
      key terms used in the statement were also defined. The new guidelines include
      general management, indications for fibrosis assessment, time to start or stop
      drug therapy, choice of drug to initiate therapy, when and how to monitor the
      patients during and after stopping drug therapy. Recommendations on the therapy
      of patients in special circumstances, including women in childbearing age,
      patients with antiviral drug resistance, concurrent viral infection, hepatic
      decompensation, patients receiving immune suppression or chemotherapy and
      patients in the setting of liver transplantation and hepatocellular carcinoma,
      are also included. 

PMID- 26201472
TI  - Transjugular intrahepatic portosystemic shunt in the treatment of portal vein
      thrombosis: a critical review of literature.
AB  - Reports of successful transjugular intrahepatic portosystemic shunt (TIPS)
      surgery in patients with portal vein thrombosis (PVT) are considered anecdotal
      owing to the technical difficulty of the procedure and potential procedure
      related complications. A literature review was undertaken to determine the
      feasibility and safety of TIPS in the treatment of PVT. All studies in which TIPS
      was attempted in patients with PVT were identified by searching through the
      PUBMED and MEDLINE databases. A total of 424 PVT patients undergoing TIPS were
      reported in 54 articles. The success rate of TIPS insertion was 67-100% in 19
      case series. Further, 85 patients with portal cavernoma underwent successful TIPS
      insertions. Three therapeutic strategies of TIPS placement were used: (1) TIPS
      placement followed by portal vein recanalization via the shunt, (2) portal vein
      recanalization via percutaneous approaches followed by TIPS placement, and (3)
      TIPS insertion between a hepatic vein and a large collateral vessel without
      portal vein recanalization. Four approaches were used to access the portal vein:
      transjugular, transhepatic, transsplenic, and transmesenteric. Intra-abdominal
      hemorrhage secondary to hepatic capsule perforation was lethal in only three
      patients. No episode of pulmonary embolism was reported. Other procedure-related
      complications were reversible. The overall incidence of shunt dysfunction and
      hepatic encephalopathy was 8-33% and 0-50%, respectively. In conclusion, the
      reviewed studies uniformly support the feasibility and safety of TIPS for PVT
      even in the presence of portal cavernoma. Further, several major issues that
      remain unresolved are discussed. 

PMID- 26201471
TI  - Model systems and clinical applications of hepatic stem cells for liver
      regeneration.
AB  - BACKGROUND: Hepatic stem cells are capable to self-renew and to differentiate
      into all types of cells in the liver, including hepatic progenitors, mature
      hepatocytes and cholangiocytes. AIMS: This review summarizes the recent advances
      in animal studies and the results of clinical trials over the last few decades.
      RESULTS: Studies in numerous animal models of liver diseases have demonstrated
      the efficacy of hepatic stem cells. Clinical studies of hepatic stem cells are
      also promising for a variety of hepatic diseases. CONCLUSIONS: With the
      accumulation of innovative and creative works, hepatic stem cells therapy will be
      a new approach for liver diseases.

PMID- 26201473
TI  - Does comorbid obesity impact quality of life outcomes in patients undergoing
      endoscopic sinus surgery?
AB  - BACKGROUND: Both obesity and chronic rhinosinusitis (CRS) are characterized by
      inflammation. Furthermore, both disease processes are independently associated
      with decreases in quality-of-life (QOL). We sought to investigate the role of
      comorbid obesity in QOL outcomes in CRS patients undergoing endoscopic sinus
      surgery (ESS). METHODS: Adult patients with medically refractory CRS (n = 241)
      were prospectively enrolled into a multi-institutional treatment outcomes
      investigation. Body mass index (BMI) calculations were used to differentiate
      patient weight groups (normal weight: 18.5 to 24.9, overweight: 25.0 to 29.9; and
      obese: >=30.0). Preoperative and postoperative QOL (Rhinosinusitis Disability
      Index [RSDI] and the 22-item Sino-Nasal Outcome Test [SNOT-22]) were evaluated
      compared across BMI groups and obesity subclasses. RESULTS: The prevalence of
      comorbid obesity was 41% (n = 99). Higher prevalence of comorbid disease was
      found across increasing BMI groups including diabetes mellitus, asthma, and
      depression. No significant differences were found in mean preoperative QOL
      measures between any BMI groups. Significant improvement between preoperative and
      postoperative QOL mean scores (p <= 0.050) was found for all BMI groups. Despite
      no significant difference in mean QOL improvement between BMI groups (p >=
      0.142), overweight and obese patients reported reduced relative mean percentage
      (%) improvement compared to normal weight participants on the RSDI total score
      (33% and 37% vs 55%, respectively) and SNOT-22 total score (29% and 40% vs 48%,
      respectively). CONCLUSION: Patients with comorbid obesity experience significant
      improvement in average QOL gains following ESS though the percentage of relative
      improvement in QOL may be decreased in patients with comorbid obesity and CRS as
      compared to those without.

PMID- 26201474
TI  - Effect of Puerarin on Expression of ICAM-1 and TNF-alpha in Kidneys of Diabetic
      Rats.
AB  - BACKGROUND: As an important factor causing end-stage renal disease, diabetic
      nephropathy is correlated with low-grade chronic inflammation and immune system
      activation. This study aimed to investigate the protective function of puerarin
      on the kidneys of diabetic rats. MATERIAL AND METHODS: A cohort of healthy male
      SD rats (7 weeks old) were randomly divided into a control group, a model group,
      and a puerarin treatment group with high (H), moderate (M), and low (L) dosage.
      After streptozotocin induction, puerarin was applied via intragastric
      administration for 8 consecutive weeks with dosages of 0.25, 0. 5 and 1.0
      mg/(kg.d) for L, M, and H groups, respectively. Fasting blood glucose (BG),
      creatinine (Scr), urea nitrogen (BUN), and urine albumin excretion rate (UAER)
      were measured, along with morphological observation of renal cells. The
      expression of intracellular adhesion molecule 1 (ICAM-1) and tumor necrosis
      factor alpha (TNF-alpha) was determined using immunohistochemical (IHC) staining,
      while renal cortex cell apoptosis was assayed by in situ end-labeling method.
      RESULTS: Model rats had significantly elevated levels of BG, Scr, BUN, and UAER
      compared to controls (p<0.05). All these increases were partially but
      significantly suppressed by puerarin (p<0.05), which also caused marked
      improvement of histopathological damages. Puerarin at each dosage significantly
      eliminated elevations of ICAM-1 and TNF-alpha levels in model rats (p<0.05), and
      decreased apoptotic indexes of renal cortex cells (p<0.05). CONCLUSIONS: Early
      stage renal damages can be significantly improved by puerarin, possibly via its
      suppression of ICAM-1 and TNF-alpha expression in diabetic rat kidneys.

PMID- 26201475
TI  - The evolution of sex: A new hypothesis based on mitochondrial mutational erosion:
      Mitochondrial mutational erosion in ancestral eukaryotes would favor the
      evolution of sex, harnessing nuclear recombination to optimize compensatory
      nuclear coadaptation.
AB  - The evolution of sex in eukaryotes represents a paradox, given the "twofold"
      fitness cost it incurs. We hypothesize that the mutational dynamics of the
      mitochondrial genome would have favored the evolution of sexual reproduction.
      Mitochondrial DNA (mtDNA) exhibits a high-mutation rate across most eukaryote
      taxa, and several lines of evidence suggest that this high rate is an ancestral
      character. This seems inexplicable given that mtDNA-encoded genes underlie the
      expression of life's most salient functions, including energy conversion. We
      propose that negative metabolic effects linked to mitochondrial mutation
      accumulation would have invoked selection for sexual recombination between
      divergent host nuclear genomes in early eukaryote lineages. This would provide a
      mechanism by which recombinant host genotypes could be rapidly shuffled and
      screened for the presence of compensatory modifiers that offset mtDNA-induced
      harm. Under this hypothesis, recombination provides the genetic variation
      necessary for compensatory nuclear coadaptation to keep pace with mitochondrial
      mutation accumulation.

PMID- 26201476
TI  - A scent of therapy: Synthetic polysulfanes with improved physico-chemical
      properties induce apoptosis in human cancer cells.
AB  - Diallyl sulfanes derived from edible plants are highly potent compounds which at
      sub-millimolar concentrations are able to induce the formation of reactive oxygen
      species (ROS) in a variety of different cells, where they often cause an altered
      redox status. The loss of cellular thiols and/or formation of ROS subsequently
      triggers a range of cellular responses, including the induction of apoptosis. A
      great disadvantage of natural diallyl mono- and polysulfanes, however, is their
      inherent insolubility in water and the extremely bad odour which limits their
      practical use in humans. Here, we present the synthesis and biological evaluation
      of two new, especially designed polysulfanes, namely the trisulfide 1-Allyl-3-(2
      ethoxyethyl)trisulfide (ATSEE) and the tetrasulfide Allyl-4-benzyltetrasulfide
      (ATTSB), which are nearly odourless. Both compounds produce O2*- radicals in
      HCT116 cells and both induce an oxidative defence signalling. Cell viability is
      especially reduced by the tetrasulfane ATTSB, with an arrest of the cell cycle in
      the G2-phase. In contrast, the trisulfane ATSEE does not inhibit the cell cycle.
      In agreement with these findings, treatment of HCT116 cells with ATTSB ultimately
      results in apoptosis whereas only limited induction of apoptosis has been
      detected for cells treated with ATSEE. We further show that antioxidative defence
      mechanisms and death response signalling run in parallel and the dominant pathway
      decides the fate of the cell. Thus, our results not only illuminate the intricate
      mode of action of certain polysulfanes; they also demonstrate that the new
      odourless tri- and tetrasulfanes exhibit a similar activity compared to their
      natural counterparts, yet are easier to handle and also deprived of the offensive
      odour which so far has prevented most practical applications of such
      polysulfanes, at least in the context of medicine. 

PMID- 26201477
TI  - Blood pressure (BP) assessment-from BP level to BP variability.
AB  - The assessment of blood pressure (BP) can be challenging in children, especially
      in very young individuals, due to their variable body size and lack of
      cooperation. In the absence of data relating BP with cardiovascular outcomes in
      children, there is a need to convert absolute BP values (in mmHg) into age-,
      gender- and height appropriate BP percentiles or Z-scores in order to compare a
      patient's BP with the BP of healthy children of the same age, but also of
      children of different ages. Traditionally, the interpretation of BP has been
      based mainly on the assessment of the BP level obtained by office, home or 24-h
      BP monitoring. Recent studies suggest that it is not only BP level (i.e. average
      BP) but also BP variability that is clinically important for the development of
      target organ damage, including the progression of chronic kidney disease. In this
      review we describe current methods to evaluate of BP level, outline available
      methods for BP variability assessment and discuss the clinical consequences of BP
      variability, including its potential role in the management of hypertension.

PMID- 26201478
TI  - Extracting biomedical events from pairs of text entities.
AB  - BACKGROUND: Huge amounts of electronic biomedical documents, such as molecular
      biology reports or genomic papers are generated daily. Nowadays, these documents
      are mainly available in the form of unstructured free texts, which require heavy
      processing for their registration into organized databases. This organization is
      instrumental for information retrieval, enabling to answer the advanced queries
      of researchers and practitioners in biology, medicine, and related fields. Hence,
      the massive data flow calls for efficient automatic methods of text-mining that
      extract high-level information, such as biomedical events, from biomedical text.
      The usual computational tools of Natural Language Processing cannot be readily
      applied to extract these biomedical events, due to the peculiarities of the
      domain. Indeed, biomedical documents contain highly domain-specific jargon and
      syntax. These documents also describe distinctive dependencies, making text
      mining in molecular biology a specific discipline. RESULTS: We address biomedical
      event extraction as the classification of pairs of text entities into the classes
      corresponding to event types. The candidate pairs of text entities are
      recursively provided to a multiclass classifier relying on Support Vector
      Machines. This recursive process extracts events involving other events as
      arguments. Compared to joint models based on Markov Random Fields, our model
      simplifies inference and hence requires shorter training and prediction times
      along with lower memory capacity. Compared to usual pipeline approaches, our
      model passes over a complex intermediate problem, while making a more extensive
      usage of sophisticated joint features between text entities. Our method focuses
      on the core event extraction of the Genia task of BioNLP challenges yielding the
      best result reported so far on the 2013 edition.

PMID- 26201479
TI  - Characterization of an Antibacterial Compound, 2-Hydroxyl Indole-3-Propanamide,
      Produced by Lactic Acid Bacteria Isolated from Fermented Batter.
AB  - Lactic acid bacteria are known to produce numerous antimicrobial compounds that
      are active against various pathogens. Here, we have purified and characterized a
      novel low-molecular-weight (LMW) antimicrobial compound produced by Lactobacillus
      and Pediococcus isolated from fermented idly and uttapam batter. The LMW compound
      was extracted from cell-free supernatant using ice-cold acetone, purified by gel
      permeation and hydrophobic interaction chromatography. It exhibited antimicrobial
      activity against Gram-positive and Gram-negative pathogenic bacteria sparing the
      probiotic strains like Lactobacillus rhamnosus. The molecular weight of the LMW
      compound was identified as 204 Da using LC-MS-ESI. In addition, the structure of
      the compound was predicted using spectroscopic methods like FTIR and NMR and
      identified as 2-hydroxyl indole-3-propanamide. The LMW compound was
      differentiated from its related compound, tryptophan, by Salkowski reaction and
      thin-layer chromatography. This novel LMW compound, 2-hydroxyl indole-3
      propanamide, may have an effective application as an antibiotic which can spare
      prevailing probiotic organisms but target only the pathogenic strains.

PMID- 26201480
TI  - Biochemical Characterization of Inducible 'Reductase' Component of Benzoate
      Dioxygenase and Phthalate Isomer Dioxygenases from Pseudomonas aeruginosa strain
      PP4.
AB  - The first step involved in the degradation of phthalate isomers (phthalate,
      isophthalate and terephthalate) is the double hydroxylation by respective
      aromatic-ring hydroxylating dioxygenases. These are two component enzymes
      consisting of 'oxygenase' and 'reductase' components. Soil isolate Pseudomonas
      aeruginosa strain PP4 degrades phthalate isomers via protocatechuate and benzoate
      via catechol 'ortho' ring cleavage pathway. Metabolic studies suggest that strain
      PP4 has carbon source-specific inducible phthalate isomer dioxygenase and
      benzoate dioxygenase. Thus, it was of interest to study the properties of
      reductase components of these enzymes. Reductase activity from phthalate isomer
      grown cells was 3-5-folds higher than benzoate grown cells. In-gel activity
      staining profile showed a reductase activity band of R f 0.56 for phthalate
      isomer-grown cells as compared to R f 0.73 from benzoate-grown cells. Partially
      purified reductase components from phthalate isomer grown cells showed K m in the
      range of 30-40 MUM and V max = 34-48 MUmol min(-1) mg(-1). However, reductase
      from benzoate grown cells showed K m = 49 MUM and V max = 10 MUmol min(-1) mg(
      1). Strikingly similar molecular and kinetic properties of reductase component
      from phthalate isomer-grown cells suggest that probably the same reductase
      component is employed in three phthalate isomer dioxygenases. However, reductase
      component is different, with respect to kinetic properties and zymogram analysis,
      from benzoate-grown cells when compared to that from phthalate isomer grown cells
      of PP4.

PMID- 26201481
TI  - An Evaluation of Kinetic Models in the Biodesulfurization of Synthetic Oil by
      Rhodococcus erythropolis ATCC 4277.
AB  - Biodesulfurization is an eco-friendly technology applied in the removal of sulfur
      from fossil fuels. This technology is based on the use of microorganisms as
      biocatalysts to convert the recalcitrant sulfur compounds into others easily
      treatable, as sulfides. Despite it has been studied during the last decades,
      there are some unsolved questions, as per example the kinetic model which
      appropriately describes the biodesulfurization globally. In this work, different
      kinetic models were tested to a batch desulfurization process using
      dibenzothiophene (DBT) as a model compound, n-dodecane as organic solvent, and
      Rhodococcus erythropolis ATCC 4277 as biocatalyst. The models were solved by
      ODE45 function in the MATLAB. Monod model was capable to describe the
      biodesulfurization process predicting all experimental data with a very good
      fitting. The coefficients of determination achieved to organic phase
      concentrations of 20, 80, and 100 % (v/v) were 0.988, 0.995, and 0.990,
      respectively. R. erythropolis ATCC 4277 presented a good affinity with the
      substrate (DBT) since the coefficients of saturation obtained to reaction medium
      containing 20, 80, and 100 % (v/v) were 0.034, 0.07, and 0.116, respectively.
      This kinetic evaluation provides an improvement in the development of
      biodesulfurization technology because it showed that a simple model is capable to
      describe the throughout process.

PMID- 26201482
TI  - X-ray Crystal Structure of Divalent Metal-Activated beta-xylosidase, RS223BX.
AB  - We report the X-ray crystal structure of a glycoside hydrolase family 43 beta
      xylosidase, RS223BX, which is strongly activated by the addition of divalent
      metal cations. The 2.69 A structure reveals that the Ca(2+) cation is located at
      the back of the active-site pocket. The Ca(2+) is held in the active site by the
      carboxylate of D85, an "extra" acid residue in comparison to other GH43 active
      sites. The Ca(2+) is in close contact with a histidine imidazole, which in turn
      is in contact with the catalytic base (D15) thus providing a mechanism for
      stabilizing the carboxylate anion of the base and achieve metal activation. The
      active-site pocket is mirrored by an "inactive-site" pocket of unknown function
      that resides on the opposite side of the monomer. 

PMID- 26201483
TI  - Dicoumarol: A Drug which Hits at Least Two Very Different Targets in Vitamin K
      Metabolism.
AB  - Dicoumarol, a symmetrical biscoumarin can be considered as the "parent" of the
      widely used anticoagulant drug, warfarin. The discovery of dicoumarol's bioactive
      properties resulted from an investigation into a mysterious cattle disease in the
      1940s. It was then developed as a pharmaceutical, but was superseded in the 1950s
      by warfarin. Both dicoumarol and warfarin antagonise the blood clotting process
      through inhibition of vitamin K epoxide reductase (VKOR). This blocks the
      recycling of vitamin K and prevents the gamma-carboxylation of glutamate residues
      in clotting factors. VKOR is an integral membrane protein and our understanding
      of the molecular mechanism of action of dicoumarol and warfarin is hampered by
      the lack of a three dimensional structure. There is consequent controversy about
      the membrane topology of VKOR, the location of the binding site for coumarin
      inhibitors and the mechanism of inhibition by these compounds. Dicoumarol (and
      warfarin) also inhibit a second enzyme, NAD(P)H quinone oxidoreductase 1 (NQO1).
      This soluble, cytoplasmic enzyme may also play a minor role in the recycling of
      vitamin K. However, its main cellular roles as an enzyme appear to be
      detoxification and the prevention of the build-up of reactive oxygen species.
      NQO1 is well characterised biochemically and structurally. Consequently,
      structure-based drug design has identified NQO1 inhibitors which have potential
      for the development of anti-cancer drugs. Many of these compounds are
      structurally related to dicoumarol and some have reduced "off target" effects.
      Therefore, it is possible that dicoumarol will become the "parent" of a second
      group of drugs.

PMID- 26201484
TI  - Nanocarriers Based Anticancer Drugs: Current Scenario and Future Perceptions.
AB  - Anticancer therapies mostly depend on the ability of the bioactives to reach
      their designated cellular and subcellular target sites, while minimizing
      accumulation and side effects at non specific sites. The development of
      nanotechnology based drug delivery systems that are able to modify the
      biodistribution, tissue uptake and pharmacokinetics of therapeutic agents is
      considered of great importance in biomedical research and treatment therapy.
      Controlled releases from nanocarriers can significantly enhance the therapeutic
      effect of a drug. Nanotechnology has the potential to revolutionize in cancer
      diagnosis and therapy. Targeted nano medicines either marketed or under
      development, are designed for the treatment of various types of cancer.
      Nanocarriers are able to reduce cytotoxic effect of the active anticancer drugs
      by increasing cancer cell targeting in comparison to conventional formulations.
      The newly developed nano devices such as quantum dots, liposomes, nanotubes,
      nanoparticles, micelles, gold nanoparticles, carbon nanotubes and solid lipid
      nanoparticles are the most promising applications for various cancer treatments.
      This review is focused on currently available information regarding
      pharmaceutical nanocarriers for cancer therapy and imaging. 

PMID- 26201485
TI  - Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic
      Nephropathy?
AB  - Diabetic nephropathy is the major cause of end-stage renal disease in Western
      societies. To date, interruption of the Renin-Angiotensin System is the most
      effective intervention for diabetic nephropathy, however these agents only slow
      progression of the disease. Thus, there is a major unmet need for new therapeutic
      targets. Aberrant activation of the receptor for advanced glycation end products
      (RAGE) is involved in the pathogenesis of diabetic nephropathy via binding to a
      variety of ligands and inciting reactive oxygen species (ROS) production,
      inflammation and fibrosis. In recent years there have been considerable efforts
      in the development of effective RAGE antagonists, however, direct RAGE targeting
      may be problematic. Glucagon like peptide-1 (GLP-1) is an incretin hormone
      released by the L-cells of the small intestine to mediate glucose-dependent
      insulin release from pancreatic islets. The incretin-based therapies, GLP-1
      receptor agonists and dipeptidylpeptidase-4 (DPP4) inhibitors, are novel glucose
      lowering agents used in type 2 diabetes. However, the extra pancreatic functions
      of GLP-1 have gained attention, including putative anti-apoptotic and anti
      inflammatory properties. In rodent models of diabetes, incretin-based therapies
      are renoprotective. Interestingly, GLP-1 has been shown to interfere with the
      signalling and expression of RAGE. The current review aims to give an overview of
      the interactions between the RAGE and incretin pathways and to discuss the
      utility of targeting the GLP-1/incretin pathway in DN. It is possible that
      indirect targeting of RAGE through GLP-1 agonism will be of clinical benefit to
      patients with diabetic nephropathy.

PMID- 26201486
TI  - Untapped Potential of Disordered Proteins in Current Druggable Human Proteome.
AB  - Current efforts in design and characterization of drugs often rely on the
      structure of their protein targets. However, a large fraction of proteins lack
      unique 3-D structures and exist as highly dynamic structural ensembles. These
      intrinsically disordered proteins are involved in pathogenesis of various human
      diseases and are highly abundant in eukaryotes. Based on a comprehensive analysis
      of the current druggable human proteome covering 12 drug classes and 18 major
      classes of drug targets we show a significant bias toward high structural
      coverage and low abundance of intrinsic disorder. We review reasons for this bias
      including widespread use of the structural information in various stages of drug
      development and characterization process and difficulty with attaining structures
      for the intrinsically disordered proteins. We also discuss future of
      intrinsically disordered proteins as drug targets. Given the overall high
      disorder content of the human proteome and current bias of the druggable human
      proteome toward structural proteins, it is inevitable that disordered proteins
      will have to raise up on the list of prospective drug targets. The protein
      disorder-assisted drug design can draw from current rational drug design
      techniques and would also need novel approaches that no longer rely on a unique
      protein structure.

PMID- 26201487
TI  - The Use of Mesenchymal Stem Cells for the Treatment of Autoimmunity: From Animals
      Models to Human Disease.
AB  - Mesenchymal stem cells are multipotent progenitors able to differentiate into
      osteoblasts, chondrocytes and adipocytes. These cells also exhibit remarkable
      immune regulatory properties, which stimulated both in vitro and in vivo
      experimental studies to unravel the underlying mechanisms as well as extensive
      clinical applications. Here, we describe the effects of MSCs on immune cells and
      their application in animal models as well as in clinical trials of autoimmune
      diseases. It should be pointed out that, while the number of clinical
      applications is increasing steadily, results should be interpreted with caution,
      in order to avoid rising false expectations. Major issues conditioning clinical
      application are the heterogeneity of MSCs and their unpredictable behavior
      following therapeutic administration. However, increasing knowledge on the
      interaction between exogenous cell and host tissue, as well as some encouraging
      clinical observations suggest that the therapeutic applications of MSCs will be
      further expanded on firmer grounds in the near future. 

PMID- 26201488
TI  - Novel Strategies in the Treatment of Pulmonary Arterial Hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a pathophysiological condition
      characterized by increased pulmonary vascular resistance (PVR), initially due to
      abnormal pulmonary vasoconstriction in response to endothelial injury. Recent
      studies confirmed the key role of endothelin (ET)-1 in the vasoconstriction and
      remodeling of pulmonary microcirculation during PAH. In responders patients,
      classical treatments for PAH are prostanoids, phosphodiesterase (PDE)-5
      inhibitors and endothelin receptor antagonists (ERAs), which target prostaglandin
      I2, nitric oxide and endothelin pathways, respectively. Randomised, placebo
      controlled trials have shown that ERAs improves haemodynamic parameters of the
      pulmonary circulation, functional capacity and clinical outcome in patients
      affected by PAH. Here, we will review the definition, classification and
      pathophysiology of PH. Furthermore, we will provide an up-to-date overview of
      currently recommended diagnostic and therapeutic work-up in PAH. 

PMID- 26201489
TI  - Silencing of Tumor Necrosis Factor Receptor-1 in Human Lung Microvascular
      Endothelial Cells Using Particle Platforms for siRNA Delivery.
AB  - Acute lung injury (ALI) and its most severe manifestation, acute respiratory
      distress syndrome (ARDS), is a clinical syndrome defined by acute hypoxemic
      respiratory failure and bilateral pulmonary infiltrates consistent with edema. In
      hospital mortality is 38.5% for AL, and 41.1% for ARDS. Activation of alveolar
      macrophages in the donor lung causes the release of pro-inflammatory chemokines
      and cytokines, such as TNF-alpha. To determine the relevance of TNF-alpha in
      disrupting bronchial endothelial cell function, we stimulated human THP-1
      macrophages with lipopolysaccharide (LPS) and used the resulting cytokine
      supplemented media to disrupt normal endothelial cell functions. Endothelial tube
      formation was disrupted in the presence of LPS-activated THP- 1 conditioned
      media, with reversal of the effect occurring in the presence of 0.1ug/ml Enbrel,
      indicating that TNF-alpha was the major serum component inhibiting endothelial
      tube formation. To facilitate lung conditioning, we tested liposomal and porous
      silicon (pSi) delivery systems for their ability to selectively silence TNFR1
      using siRNA technology. Of the three types of liposomes tested, only cationic
      liposomes had substantial endothelial uptake, with human cells taking up 10-fold
      more liposomes than their pig counterparts; however, non-specific cellular
      activation prohibited their use as immunosuppressive agents. On the other hand,
      pSi microparticles enabled the accumulation of large amounts of siRNA in
      endothelial cells compared to standard transfection with Lipofectamine((r)) LTX,
      in the absence of non-specific activation of endothelia. Silencing of TNFR1
      decreased TNF-alpha mediated inhibition of endothelial tube formation, as well as
      TNF-alpha-induced upregulation of ICAM-1, VCAM, and E-selection in human lung
      microvascular endothelial cells. 

PMID- 26201490
TI  - Understanding response patterns in dyadic conflict: An interactive approach
      combining self-construal and opponent's dominance-submissiveness.
AB  - Previous works on the effect of self-construal in interpersonal behaviours tend
      to adopt a main effect approach. The present research proposes an interactive
      approach in understanding two response patterns in dyadic conflict by combining
      self-construal and the stance of the opponent. Independent self-construal was
      hypothesised to be associated with a self-centred pattern of conflict response,
      which is characterised by taking contending responses regardless of whether the
      stance of the opponent is dominant or submissive. Relational self-construal was
      hypothesised to be associated with a tuning-in pattern of conflict response,
      which is characterised by showing contending responses when the opponent is
      submissive but yielding responses when the opponent is dominant. With trait self
      construal measured and opponent's stance manipulated, Study 1 provided initial
      support for the hypotheses. Study 2 showed a three-way interaction effect between
      trait self-construal, manipulated self-construal and the opponent's stance on
      actual conflict responses during discussion of a scenario. The effect of self
      construal manipulation was only observed among people who were low in trait
      independent self-construal and average in trait relational self-construal. The
      results pinpoint the importance of considering personal and opponent factors
      simultaneously in understanding the dynamics of dyadic conflict processes.

PMID- 26201492
TI  - Induced carotenoid accumulation in Dunaliella salina and Tetraselmis suecica by
      plant hormones and UV-C radiation.
AB  - Carotenoids prevent different degenerative diseases and improve human health.
      Microalgae are commercially exploited for carotenoids, including astaxanthin and
      beta-carotene. Two commercially important microalgae, Dunaliella salina and
      Tetraselmis suecica, were treated with plant hormones salicylic acid (SA) and
      methyl jasmonate (MJ), or by UV-C radiation (T. suecica only) and a combination
      thereof. Significant increases in total carotenoids were found for D. salina and
      T. suecica after treatment with MJ (10 MUmol/L) and SA (70-250 MUmol/L),
      respectively. T. suecica also had significant increases in total carotenoids
      following UV-C radiation compared to control cultures. Among the carotenoids,
      lutein was the highest induced carotenoid. A combination of these two treatments
      also showed a significant increase in total carotenoids and lutein for T.
      suecica, when compared to controls. Plant hormones and UV-C radiation may be
      useful tools for increasing carotenoid accumulation in green microalgae although
      the responses are species- and dose-specific and should be trialed in medium to
      large scale to explore commercial production.

PMID- 26201493
TI  - G-quadruplex forming structural motifs in the genome of Deinococcus radiodurans
      and their regulatory roles in promoter functions.
AB  - Deinococcus radiodurans displays compromised radioresistance in the presence of
      guanine quadruplex (G4)-binding drugs (G4 drugs). Genome-wide scanning showed
      islands of guanine runs (G-motif) in the upstream regions of coding sequences as
      well as in the structural regions of many genes, indicating a role for G4 DNA in
      the regulation of genome functions in this bacterium. G-motifs present upstream
      to some of the DNA damage-responsive genes like lexA, pprI, recF, recQ, mutL and
      radA were synthesized, and the formation of G4 DNA structures was probed in
      vitro. The G-motifs present at the 67th position upstream to recQ and at the
      121st position upstream to mutL produced parallel and mixed G4 DNA structures,
      respectively. Expression of beta-galactosidase under recQ and mutL promoters
      containing respective G-motifs was inhibited by G4 drugs under normal growth
      conditions in D. radiodurans. However, when such cells were exposed to gamma
      radiation, mutL promoter activity was stimulated while recQ promoter activity was
      inhibited in the presence of G4 drugs. Deletion of the G-motif from the recQ
      promoter could relax it from G4 drug repression. D. radiodurans cells treated
      with G4 drug showed reduction in recQ expression and gamma radiation resistance,
      indicating an involvement of G4 DNA in the radioresistance of this bacterium.
      These results suggest that G-motifs from D. radiodurans genome form different
      types of G4 DNA structures at least in vitro, and the recQ and mutL promoters
      seem to be differentially regulated at the levels of G4 DNA structures.

PMID- 26201494
TI  - Responses of Saccharomyces cerevisiae to nitrogen starvation in wine alcoholic
      fermentation.
AB  - Nitrogen is an important nutrient in alcoholic fermentation because its
      starvation affects both fermentation kinetics and the formation of yeast
      metabolites. In most alcoholic fermentations, yeasts have to ferment in nitrogen
      starved conditions, which requires modifications of cell functions to maintain a
      high sugar flux and enable cell survival for long periods in stressful
      conditions. In this review, we present an overview of our current understanding
      of the responses of the wine yeast Saccharomyces cerevisiae to variations of
      nitrogen availability. Adaptation to nitrogen starvation involves changes in the
      activity of signaling pathways such as target of rapamycin (TOR) and nitrogen
      catabolite repression (NCR), which are important for the remodeling of gene
      expression and the establishment of stress responses. Upon starvation, protein
      degradation pathways involving autophagy and the proteasome play a major role in
      nitrogen recycling and the adjustment of cellular activity. Recent progress in
      the understanding of the role of these mechanisms should enable advances in
      fermentation management and the design of novel targets for the selection or
      improvement of yeast strains. 

PMID- 26201495
TI  - Apparent diffusion coefficient (ADC) measurement in ovarian tumor: Effect of
      region-of-interest methods on ADC values and diagnostic ability.
AB  - PURPOSE: To investigate the difference in apparent diffusion coefficient (ADC)
      measurements of differently shaped regions of interest (ROIs) in ovarian tumors,
      and to investigate the diagnostic ability of differently shaped ROIs in
      differentiating benign from malignant ovarian tumors. MATERIALS AND METHODS:
      Fifty-four patients with ovarian tumors with a solid component were evaluated.
      The patients underwent magnetic resonance (MR) examinations including diffusion
      weighted imaging using a 3.0T MR system. Two readers measured ADCs using four ROI
      methods: freehand, square, round, and five small round ROIs. The interclass
      correlation coefficient (ICC) and repeated-measures analysis of variance were
      used to assess their measurement reliability and to compare ADCs for each ROI
      method. Receiver operating characteristic curve analysis and unpaired t-test on
      each ROI were used to differentiate benign and malignant ovarian tumors and
      assess the diagnostic ability. RESULTS: All ROI methods except the square ROI
      (0.56) showed good or excellent correlations (0.70-0.91). Minimum and mean ADC
      values differed significantly between the ROIs (P < 0.05). When using the
      freehand ROI, the minimum and mean ADC values were the lowest and highest,
      respectively. The optimal cutoff minimum and mean ADC values of each ROI for
      differentiating benign and malignant tumors were 0.81-1.06 * 10(-3) mm(2) /s and
      1.15-1.52 * 10(-3) mm(2) /s, respectively. The areas under the curve showed no
      significant differences among the ADCs in the different ROI methods (P > 0.05).
      Minimum and mean ADCs from all ROIs showed significant differences between benign
      and malignant tumors (P < 0.05). CONCLUSION: The ROI shape influences ADC values
      and the optimal cutoff ADC values for differentiating benign from malignant
      ovarian tumors.

PMID- 26201498
TI  - General defocusing particle tracking.
AB  - A General Defocusing Particle Tracking (GDPT) method is proposed for tracking the
      three-dimensional motion of particles in Lab-on-a-chip systems based on a set of
      calibration images and the normalized cross-correlation function. In comparison
      with other single-camera defocusing particle-tracking techniques, GDPT possesses
      a series of key advantages: it is applicable to particle images of arbitrary
      shapes, it is intuitive and easy to use, it can be used without advanced
      knowledge of optics and velocimetry theory, it is robust against outliers and
      overlapping particle images, and it requires only equipment which is standard in
      microfluidic laboratories. We demonstrate the method by tracking the three
      dimensional motion of 2 MUm spherical particles in a microfluidic channel using
      three different optical arrangements. The position of the particles was measured
      with an estimated uncertainty of 0.1 MUm in the in-plane direction and 2 MUm in
      the depth direction for a measurement volume of 1510 * 1270 * 160 MUm(3). A ready
      to-use GUI implementation of the method can be acquired on . 

PMID- 26201497
TI  - Urethrocutaneous fistula following hypospadias repair: regional anesthesia and
      other factors.
AB  - BACKGROUND: Urethrocutaneous fistula is a well-known complication of hypospadias
      surgery. A recent prospective study by Kundra et al. (Pediatr Anesth 2012) has
      suggested that caudal anesthesia may increase the risk of fistula formation. We
      sought to evaluate this possible association and determine if any other novel
      factors may be associated with fistula formation. METHODS: Children who underwent
      primary hypospadias repair between January 1, 1994 and March 31, 2013 at our
      tertiary care center were included in this study. Reviewed surgical data included
      repair type, duration of procedure, use of local anesthetic infiltration, and
      subcutaneous epinephrine. Analgesic factors included use of caudal and/or penile
      block, opioid usage, postoperative pain scores, and nausea/vomiting.
      Postoperative surgical complications and estimates of family household median
      income by zip code were also reviewed. RESULTS: Fistula occurrence was not
      associated with caudal or penile block, severity of postoperative pain, or
      surgeon experience. A more proximal location of the urethral meatus, longer
      operating time, and use of subcutaneous epinephrine were significantly more
      common in patients who developed fistula. As assessed by home address zip code,
      distance of more than 100 miles and median household income in the bottom 25th
      percentile of our study population were not associated with fistula, as compared
      to closer distance or higher income. CONCLUSION: In this series, we found no
      association between the use of caudal regional anesthesia and fistula formation.
      Location of the starting urethral meatus, prolonged surgical duration, and
      subcutaneous epinephrine use were associated with fistula formation. Our findings
      call into question the routine use of epinephrine in hypospadias repair.

PMID- 26201499
TI  - Direct observation of a Fermi liquid-like normal state in an iron-pnictide
      superconductor.
AB  - There are two prerequisites for understanding high-temperature (high-Tc)
      superconductivity: identifying the pairing interaction and obtaining a correct
      description of the normal state from which superconductivity emerges. The nature
      of the normal state of iron-pnictide superconductors, and the role played by
      correlations arising from partially screened interactions, are still under
      debate. Here we show that the normal state of carefully annealed electron-doped
      BaFe(2-x)Co(x)As2 at low temperatures has all the hallmark properties of a local
      Fermi liquid, with a more incoherent state emerging at elevated temperatures, an
      identification made possible using bulk-sensitive optical spectroscopy with high
      frequency and temperature resolution. The frequency dependent scattering rate
      extracted from the optical conductivity deviates from the expected scaling M2
      (omega, T) ? (homega)(2) + (ppikBT)(2) with p ~ 1.47 rather than p = 2,
      indicative of the presence of residual elastic resonant scattering. Excellent
      agreement between the experimental results and theoretical modeling allows us to
      extract the characteristic Fermi liquid scale T0 ~ 1700 K. Our results show that
      the electron-doped iron-pnictides should be regarded as weakly correlated Fermi
      liquids with a weak mass enhancement resulting from residual electron-electron
      scattering from thermally excited quasi-particles.

PMID- 26201496
TI  - The role inflammatory response genes in obstructive sleep apnea syndrome: a
      review.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has a negative impact on
      health and behavior of millions of individuals worldwide. The pathogenesis of
      this disorder is a multifactorial process related to a variety of mechanisms,
      including selective activation of inflammatory response pathways. A number of
      inflammatory factors, such as IL-6, IL-8, and TNF-alpha, can be found in high
      concentrations in subjects with OSAS and may serve as biological markers of this
      disease. The concentration of these cytokines contributes to weight gain in
      patients with OSAS and can also modify the risk of obesity-related metabolic
      disorders, especially insulin resistance. Nevertheless, the mechanisms by which
      specific genes are associated with these processes are still poorly known. In
      addition to gene expression studies, investigations aiming at the identification
      of epigenetic factors associated with OSAS are still scarce in the literature.
      The documented data support the hypothesis that the molecular changes that
      mediate inflammatory response are important mechanisms in the pathogenesis of
      OSAS, sleepiness, insulin resistance, visceral obesity, and cardiovascular
      disease, perhaps by leading to a more severe OSAS. Often, systemic changes may
      not be detected in mild OSA; however, molecular changes, which are much more
      sensitive to the mechanisms of intermittent hypoxia and oxidative stress, may be
      present. PURPOSE: This review aimed to show an updated view on the studies
      evaluating the genetic basis of inflammatory response in many aspects of OSAS and
      to highlight potential research areas not fully explored to date in this field.

PMID- 26201500
TI  - Laparoscopic versus Robotic-Assisted Radical Prostatectomy for the Treatment of
      Localised Prostate Cancer: A Systematic Review.
AB  - BACKGROUND: Prostate cancer is a prominent form of cancer diagnosed in men living
      in developed countries, for which radical prostatectomy is a common frontline
      treatment. The aim of this systematic review was to determine whether robot
      assisted laparoscopic radical prostatectomy (RALP) is more effective in the
      treatment of localised prostate cancer, compared to laparoscopic radical
      prostatectomy (LRP). METHODS: An electronic search of Medline, Scopus, Cochrane
      Database of Systematic Reviews, and Cochrane Central Register of Controlled
      Trials (Central) was performed up until December 2014. Randomised controlled
      trials (RCTs) that offered a direct comparison of laparoscopic and robotic
      techniques were eligible for inclusion in this review. RESULTS: A total of 93
      articles were identified through the literature search, of which 2 were included
      in this review. Meta-analysis of 2 studies identified a significantly higher rate
      of return of erectile function in the RALP group (relative risk (RR) 1.51; 95%
      confidence interval (CI) 1.19, 1.92). A similar effect was observed with return
      to continence function (RR 1.14; 95% CI 1.04, 1.24). CONCLUSIONS: This systematic
      review offers the first evaluation of evidence from RCTs with respect to the
      effectiveness of RALP and LRP in the treatment of localised prostate cancer.
      Preliminary results suggest that RALP was more efficient at preserving the
      erectile function and continence in comparison to LRP.

PMID- 26201501
TI  - Proteomic analysis of extracellular vesicles derived from Mycobacterium
      tuberculosis.
AB  - The release of extracellular vesicles, also known as outer membrane vesicles,
      membrane vesicles, exosomes, and microvesicles, is an evolutionarily conserved
      phenomenon from bacteria to eukaryotes. It has been reported that Mycobacterium
      tuberculosis releases extracellular vesicles harboring immunologically active
      molecules, and these extracellular vesicles have been suggested to be applicable
      in vaccine development and biomarker discovery. However, the comprehensive
      proteomic analysis has not been performed for M. tuberculosis extracellular
      vesicles. In this study, we identified a total of 287 vesicular proteins by four
      LC-MS/MS analyses with high confidence. In addition, we identified several
      vesicular proteins associated with the virulence of M. tuberculosis. This
      comprehensive proteome profile will help elucidate the pathogenic mechanism of M.
      tuberculosis. The data have been deposited to the ProteomeXchange with identifier
      PXD001160 (http://proteomecentral.proteomexchange.org/dataset/PXD001160). 

PMID- 26201502
TI  - Upper thermal tolerance of wild-type, domesticated and growth hormone-transgenic
      coho salmon Oncorhynchus kisutch.
AB  - In coho salmon Oncorhynchus kisutch, no significant differences in critical
      thermal maximum (c. 26.9 degrees  C, CTmax ) were observed among size-matched
      wild-type, domesticated, growth hormone (GH)-transgenic fish fed to satiation,
      and GH-transgenic fish on a ration-restricted diet. Instead, GH-transgenic fish
      fed to satiation had significantly higher maximum heart rate and Arrhenius
      breakpoint temperature (mean +/- s.e. = 17.3 +/- 0.1 degrees  C, TAB ). These
      results provide insight into effects of modified growth rate on temperature
      tolerance in salmonids, and can be used to assess the potential ecological
      consequences of GH-transgenic fishes should they enter natural environments with
      temperatures near their thermal tolerance limits.

PMID- 26201503
TI  - Effect of AFM probe geometry on visco-hyperelastic characterization of soft
      materials.
AB  - Atomic force microscopy (AFM) nanoindentation is very suited for nano- and
      microscale mechanical characterization of soft materials. Although the structural
      response of polymeric networks that form soft matter depends on viscous effects
      caused by the relative slippage of polymeric chains, the usual assumption made in
      the AFM-based characterization is that the specimen behaves as a purely elastic
      material and viscous forces are negligible. However, for each geometric
      configuration of the AFM tip, there will be a limit indentation rate above which
      viscous effects must be taken into account to correctly determine mechanical
      properties. A parametric finite element study conducted on 12 geometric
      configurations of a blunt cone AFM tip (overall, the study included about 200
      finite element analyses) allowed us to determine the limit indentation rate for
      each configuration. The selected tip dimensions cover commercially available
      products and account for changes in tip geometry caused by serial measurements.
      Nanoindentation rates cover typical experimental conditions set in AFM bio
      measurements on soft matter. Viscous effects appear to be more significant in the
      case of sharper tips. This implies that, if quantitative data on sample viscosity
      are not available, using a rounded indenter and carrying out experiments below
      the limit indentation rate will allow errors in the determination of mechanical
      properties to be minimized. 

PMID- 26201504
TI  - Pharmacokinetics and bioequivalence of a liquid formulation of hydroxyurea in
      children with sickle cell anemia.
AB  - Hydroxyurea (HU) is a crucial therapy for children with sickle cell anemia, but
      its off-label use is a barrier to widespread acceptance. We found HU exposure is
      not significantly altered by liquid vs capsule formulation, and weight-based
      dosing schemes provide consistent exposure. HU is recommended for all children
      starting as young as 9 months of age with sickle cell anemia (SCA; HbSS and
      HbSbetaspan(0) thalassemia); however; a paucity of pediatric data exists
      regarding the pharmacokinetics (PK) or the exposure-response relationship of HU.
      This trial aimed to characterize the PK of HU in children and to evaluate and
      compare the bioavailability of a liquid vs capsule formulation. This multicenter;
      prospective; open-label trial enrolled 39 children with SCA who provided 682
      plasma samples for PK analysis following administration of HU. Noncompartmental
      and population PK models are described. We report that liquid and capsule
      formulations of HU are bioequivalent; weight-based dosing schemes provide
      consistent drug exposure; and age-based dosing schemes are unnecessary. These
      data support the use of liquid HU in children unable to swallow capsules and in
      those whose weight precludes the use of fixed capsule formulations. Taken with
      existing safety and efficacy literature; these findings should encourage the use
      of HU across the spectrum of age and weight in children with SCA; and they should
      facilitate the expanded use of HU as recommended in the National Heart; Lung; and
      Blood Institute guidelines for individuals with SCA. 

PMID- 26201505
TI  - Utility of interim and end-of-treatment PET/CT in peripheral T-cell lymphomas: A
      review of 124 patients.
AB  - According to the updated guidelines for imaging in lymphoma, 18F-FDG positron
      emission tomography/computed tomography (PET/CT) is recommended for staging and
      evaluation of treatment response in FDG-avid lymphomas. The purpose of the study
      was to evaluate the utility of PET/CT in nodal peripheral T-cell lymphomas
      (PTCL). Patients with newly diagnosed nodal PTCL (peripheral T-cell lymphoma NOS,
      anaplastic large-cell lymphoma, or angioimmunoblastic T-cell lymphoma) seen at
      five Danish hematology centers during the period 2006 to 2012 were included, if
      they had been pretherapeutically staged with PET/CT. Medical records were
      reviewed for baseline clinical and follow-up information. Staging, interim (I
      PET), and end-of-treatment PET/CT (E-PET) studies were centrally reviewed, and
      reported using the Deauville 5-point score (DS). A total of 124 patients
      fulfilled the inclusion criteria. The median age was 58 years, and 88% received
      CHOP/CHOP-like therapy. Five years PFS and OS of the study population was 36.8%
      (95% CI 27.3-46.4) and 49.7% (95% CI 38.9-59.6), respectively. The presence of
      PET/CT-ascertained lung and/or liver involvement was associated with a worse
      outcome. The sensitivity of PET/CT for detecting biopsy-defined bone marrow
      involvement was only 18% (95% CI 4-43). An interim DS >3 was not prognostic for
      worse OS and PFS among CHOP/CHOP-like treated patients in uni- or multivariate
      analyses. A DS >3 after treatment predicted a worse prognosis. In conclusion, I
      PET was not predictive of outcome in CHOP/CHOP-like treated PTCL patients when
      using the DS. Prospective studies are needed to determine the optimal use of
      PET/CT in PTCL including the role of quantitative PET/CT analysis.

PMID- 26201506
TI  - Context-dependent effects of Y chromosome and mitochondrial haplotype on male
      locomotive activity in Drosophila melanogaster.
AB  - Some regions of the genome exhibit sexual asymmetries in inheritance and are thus
      subjected to sex-biased evolutionary forces. Maternal inheritance of
      mitochondrial DNA (mtDNA) enables mtDNA mutations harmful to males, but not
      females, to accumulate. In the face of male-harmful mtDNA mutation accumulation,
      selection will favour the evolution of compensatory modifiers in the nuclear
      genome that offset fitness losses to males. The Y chromosome is a candidate to
      host these modifiers, because it is paternally inherited, known to harbour an
      abundance of genetic variation for male fertility, and therefore likely to be
      under strong selection to uphold male viability. Here, we test for intergenomic
      interactions involving mtDNA and Y chromosomes in male Drosophila melanogaster.
      Specifically, we examine effects of each of these genomic regions, and their
      interaction, on locomotive activity, across different environmental contexts-
      both dietary and social. We found that both the mtDNA haplotype and Y chromosome
      haplotype affected activity in males assayed in an environment perceived as
      social. These effects, however, were not evident in males assayed in perceived
      solitary environments, and neither social nor solitary treatments revealed
      evidence for intergenomic interactions. Finally, the magnitude and direction of
      these genetic effects was further contingent on the diet treatment of the males.
      Thus, genes within the mtDNA and Y chromosome are involved in genotype-by
      environment interactions. These interactions might contribute to the maintenance
      of genetic variation within these asymmetrically inherited gene regions and
      complicate the dynamics of genetic interactions between the mtDNA and the Y
      chromosome.

PMID- 26201507
TI  - Recent Sexual Trauma and Adverse Health and Occupational Outcomes Among U.S.
      Service Women.
AB  - Sexual trauma is prevalent among military women, but data on potential effects
      are needed. The association of sexual trauma with health and occupational
      outcomes was investigated using longitudinal data from the Millennium Cohort
      Study. Of 13,001 U.S. service women, 1,364 (10.5%) reported recent sexual
      harassment and 374 (2.9%) recent sexual assault. Women reporting recent sexual
      harassment or assault were more likely to report poorer mental health: OR = 1.96,
      95% CI [1.71, 2.25], and OR = 3.45, 95% CI [2.67, 4.44], respectively. They
      reported poorer physical health: OR = 1.39, 95% CI [1.20, 1.62], and OR = 1.39,
      95% CI [1.04, 1.85], respectively. They reported difficulties in work/activities
      due to emotional health: OR = 1.80, 95% CI [1.59, 2.04], and OR = 2.70, 95% CI
      [2.12, 3.44], respectively. They also reported difficulties with physical health:
      OR = 1.55, 95% CI [1.37, 1.75], and OR = 1.52 95% CI [1.20, 1.91], respectively,
      after adjustment for demographic, military, health, and prior sexual trauma
      characteristics. Recent sexual harassment was associated with demotion, OR =
      1.47, 95% CI [1.12, 1.93]. Findings demonstrated that sexual trauma represents a
      potential threat to military operational readiness and draws attention to the
      importance of prevention strategies and services to reduce the burden of sexual
      trauma on military victims.

PMID- 26201508
TI  - The Relationship Between Artificial and Second Language Learning.
AB  - Artificial language learning (ALL) experiments have become an important tool in
      exploring principles of language and language learning. A persistent question in
      all of this work, however, is whether ALL engages the linguistic system and
      whether ALL studies are ecologically valid assessments of natural language
      ability. In the present study, we considered these questions by examining the
      relationship between performance in an ALL task and second language learning
      ability. Participants enrolled in a Spanish language class were evaluated using a
      number of different measures of Spanish ability and classroom performance, which
      was compared to IQ and a number of different measures of ALL performance. The
      results show that success in ALL experiments, particularly more complex
      artificial languages, correlates positively with indices of L2 learning even
      after controlling for IQ. These findings provide a key link between studies
      involving ALL and our understanding of second language learning in the classroom.

PMID- 26201509
TI  - High-purity recombinant osteopontin N-terminal domain.

PMID- 26201511
TI  - Defibrillation testing is not required during routine ICD implantation.

PMID- 26201510
TI  - Effectiveness of two year balance training programme on prevention of fall
      induced injuries in at risk women aged 75-85 living in community: Ossebo
      randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of a two year exercise programme of
      progressive balance retraining in reducing injurious falls among women aged 75-85
      at increased risk of falls and injuries and living in the community. DESIGN:
      Pragmatic multicentre, two arm, parallel group, randomised controlled trial.
      SETTING: 20 study sites in 16 medium to large cities throughout France.
      PARTICIPANTS: 706 women aged 75-85, living in their own home, and with diminished
      balance and gait capacities, randomly allocated to the experimental intervention
      group (exercise programme, n=352) or the control group (no intervention, n=354).
      INTERVENTION: Weekly supervised group sessions of progressive balance training
      offered in community based premises for two years, supplemented by individually
      prescribed home exercises. OUTCOME MEASURES: A geriatrician blinded to group
      assignment classified falls into one of three categories (no consequence,
      moderate, severe) based on physical damage and medical care. The primary outcome
      was the rate of injurious falls (moderate and severe). The two groups were
      compared for rates of injurious falls with a "shared frailty" model. Other
      outcomes included the rates of all falls, physical functional capacities (balance
      and motor function test results), fear of falling (FES-I), physical activity
      level, and perceived health related quality of life (SF-36). Analysis was by
      intention to treat. RESULTS: There were 305 injurious falls in the intervention
      group and 397 in the control group (hazard ratio 0.81, 95% confidence interval
      0.67 to 0.99). The difference in severe injuries (68 in intervention group v 87
      in control group) was of the same order of magnitude (0.83, 0.60 to 1.16). At two
      years, women in the intervention group performed significantly better on all
      physical tests and had significantly better perception of their overall physical
      function than women in the control group. Among women who started the
      intervention (n=294), the median number of group sessions attended was 53
      (interquartile range 16-71). Five injurious falls related to the intervention
      were recorded. CONCLUSION: A two year progressive balance retraining programme
      combining weekly group and individual sessions was effective in reducing
      injurious falls and in improving measured and perceived physical function in
      women aged 75-85 at risk of falling.Trial registration ClinicalTrials.gov
      (NCT00545350).

PMID- 26201512
TI  - Undiagnosed nephrogenic diabetes insipidus as a cause of acute urinary retention
      in a young soldier.
AB  - We present a case of undiagnosed nephrogenic diabetes insipidus as a cause of
      acute urinary retention in a 21-year-old male soldier. Soldiers live in close
      quarters, and have a regimented lifestyle that may not allow for frequent
      voiding; therefore, undiagnosed nephrogenic diabetes insipidus may result in
      acute urinary retention.

PMID- 26201513
TI  - Diagnosis of bacteremia in pediatric oncologic patients by in-house real-time
      PCR.
AB  - BACKGROUND: Infections are the major cause of morbidity and mortality in children
      with cancer. Gaining a favorable prognosis for these patients depends on
      selecting the appropriate therapy, which in turn depends on rapid and accurate
      microbiological diagnosis. This study employed real-time PCR (qPCR) to identify
      the main pathogens causing bloodstream infection (BSI) in patients treated at the
      Pediatric Oncology Institute IOP-GRAACC-UNIFESP-Brazil. Antimicrobial resistance
      genes were also investigated using this methodology. METHODS: A total of 248
      samples from BACTEC(r) blood culture bottles and 99 whole-blood samples collected
      in tubes containing EDTA K2 Gel were isolated from 137 patients. All samples were
      screened by specific Gram probes for multiplex qPCR. Seventeen sequences were
      evaluated using gender-specific TaqMan probes and the resistance genes bla SHV,
      bla TEM, bla CTX, bla KPC, bla IMP, bla SPM, bla VIM, vanA, vanB and mecA were
      detected using the SYBR Green method. RESULTS: Positive qPCR results were
      obtained in 112 of the blood culture bottles (112/124), and 90 % agreement was
      observed between phenotypic and molecular microbial detection methods. For
      bacterial and fungal identification, the performance test showed: sensitivity 87
      %; specificity 91 %; NPV 90 %; PPV 89 % and accuracy of 89 % when compared with
      the phenotypic method. The mecA gene was detected in 37 samples, extended
      spectrum beta-lactamases were detected in six samples and metallo-beta-lactamase
      coding genes in four samples, with 60 % concordance between the two methods. The
      qPCR on whole blood detected eight samples possessing the mecA gene and one
      sample harboring the vanB gene. The bla KPC, bla VIM, bla IMP and bla SHV genes
      were not detected in this study. CONCLUSION: Real-time PCR is a useful tool in
      the early identification of pathogens and antimicrobial resistance genes from
      bloodstream infections of pediatric oncologic patients.

PMID- 26201514
TI  - How do stone attenuation and skin-to-stone distance in computed tomography
      influence the performance of shock wave lithotripsy in ureteral stone disease?
AB  - BACKGROUND: Shock wave lithotripsy (SWL) is a noninvasive, safe, and efficient
      treatment option for ureteral stones. Depending on stone location and size, the
      overall stone-free rate (SFR) varies significantly. Failure of stone
      disintegration results in unnecessary exposure to shock waves and radiation and
      requires alternative treatment procedures, which increases medical costs. It is
      therefore important to identify predictors of treatment success or failure in
      patients who are potential candidates for SWL before treatment. Nowadays,
      noncontrast computed tomography (NCCT) provides reliable information on stone
      location, size, number, and total stone burden. The impact of additional
      information provided by NCCT, such as skin-to-stone distance (SSD) and mean
      attenuation value (MAV), on stone fragmentation in ureteral stone disease has
      hardly been investigated separately so far. Thus, the objective of this study was
      to assess the influence of stone attenuation, SSD and body mass index (BMI) on
      the outcome of SWL in ureteral stones. METHODS: We reviewed the medical records
      of 104 patients (80 men, 24 women) with ureteral stone disease treated
      consecutively at our institution with SWL between 2010 and 2013. MAV in
      Hounsfield Units (HU) and SSD were determined by analyzing noncontrast computed
      tomography images. Outcome of SWL was defined as successful (visible stone
      fragmentation on kidney, ureter, and bladder film (KUB)) or failed (absent
      fragmentation on KUB). RESULTS: Overall success of SWL was 50% (52 patients).
      Median stone attenuation was 956.9 HU (range 495-1210.8) in the group with
      successful disintegration and 944.6 (range 237-1302) in the patients who had
      absent or insufficient fragmentation. Median SSD was 125 mm (range 81-165 mm) in
      the group treated successfully and 141 mm (range 108-172 mm) in the patients with
      treatment failure. Unlike MAV (p = 0.37), SSD (p < 0.001) and BMI (p = 0.008)
      significantly correlated with treatment outcome. CONCLUSION: The choice of
      treatment for ureteral stones should be based on stone location and size as
      considered in the AUA and EAU guidelines on urinary stone disease. In ambiguous
      cases, SSD and BMI can be used to assist in the decision. In this study, MAV
      showed no correlation with fragmentation rate of SWL.

PMID- 26201516
TI  - Minimally invasive, maximal outcomes in breast surgery.
AB  - The contemporary treatment of breast cancer has evolved in response to numerous
      randomised control trials which have aided in the development of guidelines for
      effective treatment. Breast cancer surgery has progressed thanks in part to the
      advances made in chemotherapy, radiation therapy and early detection. As these
      advances continue the field of surgery needs to progress in tandem to maximise
      survival outcomes but to also minimise morbidity. 

PMID- 26201515
TI  - Akt kinase C-terminal modifications control activation loop dephosphorylation and
      enhance insulin response.
AB  - The Akt protein kinase, also known as protein kinase B, plays key roles in
      insulin receptor signalling and regulates cell growth, survival and metabolism.
      Recently, we described a mechanism to enhance Akt phosphorylation that restricts
      access of cellular phosphatases to the Akt activation loop (Thr(308) in Akt1 or
      protein kinase B isoform alpha) in an ATP-dependent manner. In the present paper,
      we describe a distinct mechanism to control Thr(308) dephosphorylation and thus
      Akt deactivation that depends on intramolecular interactions of Akt C-terminal
      sequences with its kinase domain. Modifications of amino acids surrounding the
      Akt1 C-terminal mTORC2 (mammalian target of rapamycin complex 2) phosphorylation
      site (Ser(473)) increased phosphatase resistance of the phosphorylated activation
      loop (pThr(308)) and amplified Akt phosphorylation. Furthermore, the phosphatase
      resistant Akt was refractory to ceramide-dependent dephosphorylation and
      amplified insulin-dependent Thr(308) phosphorylation in a regulated fashion.
      Collectively, these results suggest that the Akt C-terminal hydrophobic groove is
      a target for the development of agents that enhance Akt phosphorylation by
      insulin. 

PMID- 26201517
TI  - Incidence of infection according to intravenous immunoglobulin use in autologous
      hematopoietic stem cell transplant recipients with multiple myeloma.
AB  - BACKGROUND: Although intravenous immunoglobulin (IVIG) is not routinely
      recommended, many centers still use IVIG during the post-hematopoietic stem cell
      transplant (HSCT) period. METHOD: A total of 162 multiple myeloma (MM) patients
      who underwent autologous (auto-) HSCT between January 2008 and June 2013 were
      retrospectively reviewed. Primary objective was determination of the impact of
      IVIG on post-transplant infection, and secondary objectives included
      identification of overall incidence of infection, type of infection, and risk
      factors for infection after auto-HSCT in MM patients. RESULTS: After auto-HSCT,
      53 of 162 patients (32.7%) experienced 104 infectious events. Upper respiratory
      infection was most common (n = 31, 29.8%) and pneumonia (n = 27, 26.0%) and
      herpes zoster (n = 15, 14.4%) came next. Among the identifiable organisms causing
      respiratory infection, influenza virus (n = 10) and Pneumococcus (n = 9) were
      predominant. Incidence of infection was not statistically different according to
      IVIG use (34.8% in IVIG (-) vs. 31.3% in IVIG (+), P = 0.631). Incidence of
      infection requiring hospitalization and multiple episodes of infection showed no
      difference between the groups (P = 0.147, P = 0.156). In a Cox proportional
      hazard model, none of the factors including age, gender, type of disease, stage,
      tandem (vs. single) transplantation,and IVIG was prognostic for infectious event
      after auto-HSCT (P = 0.955, hazard ratio 0.980 with 95% confidence interval 0.481
      1.997 for IVIG). CONCLUSION: In auto-HSCT recipients with MM, incidence of post
      transplant infection was not different according to prophylactic IVIG use.

PMID- 26201518
TI  - Hypoxic hepatitis: a challenging diagnosis.
AB  - Hypoxic hepatitis (HH), one of the most common causes of acute liver injury, has
      a prevalence of up to 10% of admissions in intensive care units across the world.
      Inadequate oxygen uptake by the hepatocytes resulting in centrilobular necrosis
      associated with abnormally raised levels of the serum transaminases (ALT, AST) in
      patients with clinical history of cardiac, respiratory, or circulatory failures
      is the key feature of this condition. Abstracts, reviews, case reports, and
      research letters from various sources such as Pubmed, Proquest, Ovid, Google
      Scholar, and ISI Web of Knowledge dating from 1970 to 2011 were read and analyzed
      thoroughly. A study of 100 patients with HH, carried out from 2009 to 2010 at
      Tongji Hospital of Tongji University, Shanghai, People's Republic of China, is
      also documented. The contributing factors leading to HH are passive congestion,
      ischemia, and arterial hypoxemia of the liver. Ischemia/reperfusion injury also
      has a major role in HH. Some of its complications are spontaneous hypoglycemia, a
      high level of serum ammonia, and respiratory insufficiency due to hepatopulmonary
      syndrome. The therapy of HH lies mainly in the treatment of the main underlying
      causes, and this leads to the successful reversion of HH. The aim of this review
      is to present a simplified concept about the etiology, pathophysiology,
      mechanism, clinical manifestations, diagnosis, and treatment of HH. 

PMID- 26201519
TI  - Systematic review: extracorporeal bio-artificial liver-support system for liver
      failure.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is the only effective long
      term treatment for liver failure by now. However, it is not yet a perfect choice
      due to donor-organ shortage and the need of a lifelong immunosuppressive therapy.
      Therefore, it is necessary to find a new approach to fighting the disease.
      Several published clinical trials have reported the therapeutic effect of bio
      artificial liver (BAL) for liver failure. OBJECTIVE: To overview and evaluate the
      current clinical application and outcomes of extracorporeal BAL support system
      during the past 15 years. METHODS: Relevant studies were retrieved from PubMed
      and Cochrane Library databases. Independent assessments and the final consensus
      decision were performed by three independent reviewers. Acceptable study designs
      included randomized controlled trials, controlled clinical trials, and case
      reports. A total of 31 studies were tabulated and critically appraised in terms
      of characteristics, methods, and outcomes. RESULTS: There was a trend of falling
      into the normal ranges with the clinical and biochemical parameters after the BAL
      treatment. The neurological status of most patients was improved or stabilized
      during BAL treatment as well. No significant effect on survival could be seen
      after the BAL treatment. CONCLUSIONS: Although BAL system proved to be a success
      in some clinical cases reported, it still needs to be improved greatly.

PMID- 26201520
TI  - Natural history of HCV infection.
AB  - BACKGROUND: There is much controversy surrounding the natural history of
      hepatitis C virus (HCV) infection. AIMS: The aim of this review was to review the
      natural history of HCV infection. METHODS: Published English literature was
      searched via pubmed and then reviewed. RESULTS: Approximately, 75-85% of HCV
      infected persons will progress to chronic HCV infection. The rate of chronic HCV
      infection is affected by a person's age, gender, race, and viral immune response.
      Once chronic HCV infection develops, there are external and host factors that can
      increase the risk of progression of liver disease. Progression of chronic HCV
      infection is not linear in time, probably because many cofactors change the rate
      of development of fibrosis, cirrhosis, and hepatocellular carcinoma. Factors
      linked with aggressive disease progression include age at infection, duration of
      infection, heavy alcohol use, co-infections with HIV or hepatitis B virus, male
      sex, steatosis, insulin resistance (and factors associated with the metabolic
      syndrome), and host genetics. However, the relative importance of many and varied
      factors remains uncertain, and further research efforts should be directed toward
      design of predictive models for effective risk stratification. Interferon-based
      therapy, particularly among those achieving a sustained virologic response (SVR),
      is associated with improved fibrosis and inflammation scores, reduced incidence
      of hepatocellular carcinoma, and prolonged life expectancy. CONCLUSIONS: Despite
      the progress in understanding the factors affecting the natural history of HCV
      infection, a great deal remains to be learnt.

PMID- 26201521
TI  - Naturally occurring core immune-escape and carboxy-terminal mutations?truncations
      in patients with e antigen negative chronic hepatitis B.
AB  - INTRODUCTION: Hepatocellular injury is often progressive in patients with
      hepatitis B e antigen negative chronic hepatitis B (HBeAg -ve CHB). There is
      scant data on association of core mutations occurring in patients with HBeAg -ve
      CHB with severity of liver disease. MATERIALS AND METHODS: Hundred and eighteen
      patients with chronic infection who were HBeAg negative, anti-HBe, and HBV DNA
      positive were enrolled. Precore and core regions were amplified, sequenced, and
      analyzed for precore, T helper, cytotoxic T lymphocytes (CTLs), B-cell epitope,
      and core carboxy-terminal region mutations. RESULTS: Majority of patients were
      infected with HBV genotype D: 96 (81%) [D1: 16, D2: 55 and D5: 25] followed by
      genotype A1: 15 (13%) and genotype C: 7 (6%) [C1: 5 and unidentified subgenotype
      C: 2]. Classical (A1896) as well as nonclassical precore region mutations were
      detected in 30 (25%) and in 9 (7.6%) patients, respectively. Core immune escape,
      core carboxy-terminal mutations and truncations were detected in 61 (52%), 11
      (9.3%), and 14 (12%) patients, respectively. Three core immune escape mutations
      were significantly higher in patients with coexisting precore stop codon compared
      with patients without precore stop codon mutation, cT12S (43 vs. 8%, p < 0.001),
      cS21T (16 vs. 3.4%, p < 0.026), and cE77D (30 vs. 4.5%, p < 0.002). When
      frequency of core immune escape mutations was compared among CHB and
      decompensated patients, and cT12S: (27 vs. 10%, p < 0.05), cS21T (16 vs. 1.35%, p
      < 0.01), cT67P/N: (20 vs. 4%, p < 0.001), cE113D (11.37 vs. 1.35%, p < 0.05), and
      cP130T/Q (7 vs. 0%, p < 0.001) mutations were found to be significantly higher in
      decompensated patients. CONCLUSION: Core immune-escape mutations cT12S, cS21T,
      cT67P, cE113D, and cP130T/Q are significantly higher in decompensated liver
      disease patients and could influence the severity of liver disease in HBeAg -ve
      CHB patients.

PMID- 26201522
TI  - A Novel prognostic scoring system to predict 3-month mortality risk in patients
      with acute-on-chronic liver failure in hepatitis B: a retrospective cohort study.
AB  - PURPOSE: The present study was done to establish an objective, sensitive
      prognostic scoring system and to determine the applicability of this model in
      predicting the 3-month mortality of patients with acute-on-chronic liver failure
      in hepatitis B (ACLFB). METHODS: We developed a novel prognostic scoring system,
      calculated from six clinical indices including serum total bilirubin, prothrombin
      activity, serum creatinine, hepatic encephalopathy, infections, and the depth of
      ascites from 499 patients with ACLFB. Differences in the sensitivity,
      specificity, and practicality of a Novel prognostic scoring system and the model
      of end-stage liver disease (MELD) were analyzed. RESULTS: The areas under the
      receiver operating characteristic curve (ROC) for the Novel scoring systems and
      MELD scoring systems were 0.967 (95% CI, 0.956-0.977) and 0.900 (95% CI, 0.878
      0.922), respectively. The analysis of the ROC curve indicated that the Novel
      scoring systems were an exact, pertinent, and objective prognostic model with
      greater accuracy than the MELD. In the Novel scoring systems, the survival rate
      of these patients whose scores ranged from 2 to 6 was 98.80%, while for those
      whose scores point at 7 and 15, the mortality rates were 8.70% (2/23) and 95.45%
      (21/22), respectively, and the mortality rate of these patients whose scores were
      16 and above was 100.00%. However, in the MELD prognostic scoring systems, there
      were no score ranges with 100.00% survival rate. CONCLUSIONS: We developed an
      objective, pertinent, and sensitive prognostic scoring system that predicted the
      3-month mortality of patients with ACLFB with greater accuracy than the MELD.

PMID- 26201523
TI  - Entecavir treatment prevents disease progression in hepatitis B virus-related
      acute-on-chronic liver failure: establishment of a novel logistical regression
      model.
AB  - BACKGROUND: Hepatitis B-related acute-on-chronic liver failure (ACLF) has a poor
      prognosis with very high mortality. Unfortunately, most prognostic predictive
      models of liver failure are complicated and offer suboptimal sensitivity.
      Experience in entecavir (ETV)-treated patients with hepatitis B virus (HBV)-ACLF
      is limited. AIMS: This study was designed to evaluate the efficacy and safety of
      ETV in patients with HBV-ACLF and to develop a novel model (Tongji prognostic
      predictor model, TPPM) for prognostic prediction of HBV-ACLF patients. METHOD: In
      this retrospective study, 248 patients with HBV-ACLF were enrolled. There were no
      significant differences in baseline clinical and virologic characteristics
      between patients treated with and without ETV. RESULTS: The 1- and 3-month
      survival rates of patients in the ETV-treated group (n = 124) were 72.58 and
      61.29%, respectively, significantly higher than that in NA-free group (n = 124),
      which were 53.23 and 45.97%, respectively. By Hosmor and Lemeshow test, TPPM for
      HBV-ACLF had a very good degree of fit with disease prognosis. Based on this
      unique group of patients, the TPPM scoring offered a better prediction value in
      both specificity and sensitivity for 3-month mortality of patients with HBV-ACLF
      compared with MELD scoring system with statistically significant difference. In
      the patients with HBV-ACLF, using a cutoff of 0.22 for 3-month predicted
      mortality by TPPM, the positive predictive value was 93.6% and negative
      predictive value 91.3%. CONCLUSION: ETV treatment prevented disease progression
      and increased the survival of patients with HBV-ACLF. The established TPPM
      scoring system offers superior predictor value in both specificity and
      sensitivity for HBV-ACLF patients when compared with MELD.

PMID- 26201524
TI  - Transarterial chemoembolization can prolong survival for patients with metastatic
      hepatocellular carcinoma: a propensity score matching analysis.
AB  - BACKGROUND: In Asian countries, transarterial chemoembolization (TACE) is widely
      applied in hepatocellular carcinoma (HCC) patients with extra-hepatic metastasis
      in the absence of main portal vein thrombosis. However, its survival benefit is
      unclear. The study aimed to analyze the role of TACE in patients with metastatic
      HCC. METHODS: From 2002 to 2009, 2,165 consecutive HCC patients were
      retrospectively reviewed. Of the 893 Barcelona Clinic Liver Cancer stage C
      patients, 105 who had extra-hepatic metastasis on initial presentation without
      main portal vein thrombosis were enrolled, including 46 who received TACE (TACE
      group) and 59 who received supportive treatment (control group). Factors
      associated with survival were evaluated by multivariate analysis. Survival
      between the two groups was compared by propensity score matching analysis.
      RESULTS: Median survival in the TACE and control groups was 6.6 and 3.2 months,
      respectively (p < 0.001). By multivariate analysis, TACE [hazard ratio (HR) =
      0.476, p = 0.002], tumor size >10 cm (HR = 1.606, p = 0.045), and alpha
      fetoprotein (AFP) >2,000 ng ml(-1) (HR = 1.599, p = 0.037) were factors
      associated with survival. After propensity score matching analysis, a better
      survival was noted in the TACE group (median survival 4.0 vs. 3.0 months, p =
      0.029). Subgroup analysis showed that patients with tumor size <=10 cm and AFP
      levels <=2,000 ng ml(-1) had the best survival from TACE. Smaller tumor size is
      the only independent predictor for survival longer than 6 months in patients
      receiving TACE. CONCLUSIONS: TACE provides survival benefit for metastatic HCC
      patients. Prospective randomized controlled trials are warranted to delineate the
      role of combining TACE with sorafenib or other treatment for metastatic HCC.

PMID- 26201525
TI  - Clinical features and prognosis of hepatocellular carcinoma in Mongolia: a
      multicentre study.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is the most common cancer in Mongolia. We
      aimed to investigate the clinical features, therapeutic modalities, overall
      survival and prognostic factors for Mongolian patients with HCC. METHOD: One
      hundred ninety-five patients with HCC were consecutively enroled in our study.
      RESULTS: The mean age was 61.7 years. The most common etiology for HCC was HCV
      infection (n = 89, 45.6%), followed by HBV infection (n = 67, 34.4%). The mean
      tumor diameter was 6.0 +/- 2.6 cm. Only 29 (14.9%) patients had a single lesion,
      while 39 (20.2%) had >3 lesions. Extrahepatic metastasis to lung (n = 23), bone
      (n = 10) and lymph node (n = 3) were detected in 36 (18.5%) patients. Most
      patients had advanced HCC-88 (45.1%) in stage III and 57 (29.2%) in stage IV.
      Surgical resection was performed in 27 (13.8%) patients, RFA in 23 (11.8%) and
      TACE in 107 (54.9%). When all the patients were categorized as 'treated' (n =
      156) and 'not treated' (n = 39), the 3-year survival was significantly lower in
      the 'not treated' group than in the 'treated' group (11 vs. 0%, P < 0.001). Tumor
      diameter (<3 cm vs. >=3 cm), extrahepatic metastasis, TNM stage (I/II vs. III/IV)
      and treatment (or supportive care) were selected as independent predictors for
      survival. CONCLUSIONS: High proportion of patients with HCC in Mongolia is
      diagnosed at an advanced stage and survival of these patients is lower compared
      to other countries. A surveillance system and referral policy for high-risk
      groups should be urgently established and implemented in Mongolia.

PMID- 26201526
TI  - Circulating endotoxin and interleukin-6 levels are associated with Doppler
      evaluated pulmonary vascular resistance in cirrhotic patients.
AB  - PURPOSE: Endotoxin and interleukin-6 levels (IL-6) have been involved in the
      development of pulmonary hypertension (PH) in non-cirrhotic experimental models
      and subjects. High circulating levels of both substances have been detected in
      cirrhosis. The association between circulating endotoxin and IL-6 levels and
      echocardiographically evaluated pulmonary vascular resistance (PVR) in cirrhotic
      patients are investigated. METHODS: Thirty-seven cirrhotic patients were studied:
      25 with PVR <120 dynes s cm(-5) (group 1) and 12 with PVR >120 dynes s cm(-5)
      (group 2). Plasma endotoxin and serum IL-6 levels were measured. The PVR and
      cardiac output (CO) by Doppler ultrasound, mean arterial pressure (MAP), and
      systemic vascular resistance (SVR) as the ratio MAP/CO were evaluated. RESULTS:
      Child-Pugh scores, MAP, CO, and SVR were similar in both groups. Endotoxin levels
      were correlated significantly with IL-6 levels (r = 0.342; P = 0.03). Endotoxin
      and IL-6 levels were significantly higher in group 2 compared to group 1 (2.26
      [0.39-8.4] vs. 0.85 [0.37-7.6] EU/mL; P = 0.04 and 37.4 [7.85-106.5] vs. 8.36
      [3.15-53.7] pg/mL; P < 0.001, respectively). The PVR was correlated significantly
      with endotoxin levels in group 2 (r = 0.587; P = 0.04) and with IL-6 levels in
      group 1 (r = 0.529; P = 0.01) and group 2 (r = 0.760; P = 0.004), respectively.
      CONCLUSIONS: Our results suggest that endotoxin and IL-6 may contribute to
      cirrhosis-associated PH. In this regard, modulation of these substances could
      improve pulmonary pressures in cirrhotic patients.

PMID- 26201527
TI  - Complete spectrum of AMA-M2 positive liver disease in north India.
AB  - PURPOSE: This study describes the clinical, histological, and genetic profile of
      AMA-M2 positive liver disease in north India. METHODS: Over 13.5 years, 11,221
      patients suspected of AiLD (autoimmune liver disease) and negative for viral
      markers were screened for autoantibodies, ANA, ASMA, AMA, and LKM, by indirect
      immunofluorescence. Of these patients, 135 were AMA positive and 132 AMA-M2
      positive. Clinical presentation of most of these patients was neither typical of
      AIH nor PBC. Sera of these patients were further tested for gp 210 and Sp 100.
      Fifty consecutive consenting patients were typed for HLA class II alleles DR and
      DQ and their clinical, biochemical, histology and genetic profiles were reviewed
      to characterize the disease spectrum in north India. RESULTS: Only 22 of 50
      patients had liver histology reports, and could be categorized on the basis of
      the criteria by Chazouillers et al. Of these 22, 13 had overlap syndrome, eight
      had classical PBC, whereas one had probable PBC. The remaining 28 could not be
      suitably categorized due to lack of liver histology. HLA DRB1*03 was found to be
      significantly associated with the disease in North Indian population. CONCLUSION:
      This 13.5-year study demonstrates a definite rising annual incidence of AMA-M2
      positive liver disease in north India. Complete evaluation of 50 patients
      indicated that a hepatitic variant of PBC (PBC-AIH), which is significantly
      associated with DRB1*03, predominates in north India.

PMID- 26201528
TI  - Low incidence and prevalence of primary biliary cirrhosis in Canterbury, New
      Zealand: a population-based study.
AB  - PURPOSE: Epidemiological data on primary biliary cirrhosis (PBC) in the Southern
      Hemisphere is scarce. Our aim was to perform a population-based epidemiological
      study of PBC in Canterbury, New Zealand. METHODS: Multiple case-finding methods
      were employed. All public and private, adult and pediatric outpatient clinics,
      hospital discharge summaries, and laboratory and pathology reports were searched
      to identify all cases in the region. Cases were included if at least two of the
      following criteria were fulfilled: (1) positive anti-mitochondrial antibodies,
      (2) elevated alkaline phosphatase for greater than 6 months, and (3) compatible
      liver histology. RESULTS: A total of 71 cases of PBC were included. The incidence
      in 2008 was 0.8 (95% confidence interval (CI) 0.1-1.6) per 100,000. The point
      prevalence on December 31, 2008 was 9.9 (95% CI 7.1-12.7) per 100,000. Male to
      female ratio was 1:11. At presentation, 45% were asymptomatic. Age at diagnosis
      peaked at the seventh decade with mean age at diagnosis of 61 (95% CI 58-64).
      CONCLUSIONS: This is the first population-based epidemiological study of PBC
      conducted in New Zealand and only the second in the Southern Hemisphere. The
      incidence and prevalence are lower than the Northern Hemisphere, even though the
      majority of our population has shared genetic background with some of these
      countries. Our study has provided further support to the hypothesis that there
      may be a protective effect or lack of a risk factor for PBC in New Zealand.

PMID- 26201529
TI  - Erratum to: Asian-Pacific consensus statement on the management of chronic
      hepatitis B: a 2012 update.

PMID- 26201530
TI  - Intrapartum assessment of caput succedaneum by transperineal ultrasound: a two
      centre pilot study.
AB  - Digital assessments of caput succedaneum are subjective; however, caput
      succedaneum can also be expressed as ultrasound measured skin-skull distance
      (SSD). In this study, we aimed to compare the clinical and ultrasound assessment
      of caput succedaneum (caput) in nulliparous women in the first stage of labour.
      Furthermore, we aimed to investigate the repeatability of ultrasound
      measurements. We observed a significant but low correlation between clinical and
      ultrasound assessments (Kappa value 0.29; P < 0.01). Interobserver repeatability
      for SSD showed an intraclass correlation coefficient of 0.96 (95% CI, 0.93-0.98).
      The mean difference for the caput measurements was -0.4 mm (95% CI, -0.85 to
      0.05), and limits of agreement were -3.44 to 2.64 mm. We conclude that ultrasound
      measured SSD is an objective expression of caput with significant correlation
      with clinical assessment.

PMID- 26201531
TI  - Cnidarian Neurotoxic Peptides Affecting Central Nervous System Targets.
AB  - Natural products from animal venoms have been used widely in the discovery of
      novel molecules with particular biological activities that enable their use as
      potential drug candidates. The phylum Cnidaria (jellyfish, sea anemones, corals
      zoanthids, hydrozoans, etc.) is the most ancient venomous phylum on earth. Its
      venoms are composed of a complex mixture of peptidic compounds with neurotoxic
      and cytolitic properties that have shown activity on mammalian systems despite
      the fact that they are naturally targeted against fish and invertebrate preys,
      mainly crustaceans. For this reason, cnidarian venoms are an interesting and vast
      source of molecules with a remarkable activity on central nervous system,
      targeting mainly voltage-gated ion channels, ASIC channels, and TRPV1 receptors.
      In this brief review, we list the amino acid sequences of most cnidarian
      neurotoxic peptides reported to date. Additionally, we propose the inclusion of a
      new type of voltage-gated sea anemone sodium channel toxins based on the most
      recent reports.

PMID- 26201532
TI  - Computational Analysis and Functional Prediction of Ubiquitin Hypothetical
      Protein: A Possible Target in Parkinson Disease.
AB  - Parkinson's disease (PD) is a high prevalent progressive neurodegenerative
      disorder characterized by degeneration of dopaminergic neurons and
      intracytoplasmatic aggregation of alpha-synuclein called Lewy Bodies. Anomalies
      in the proteasomal and endosomal ubiquitin related degradation of alpha-synuclein
      have been related with PD. Among the different proteins described in ubiquitin
      pathway, the hypothetical protein CAB55973.1 was identified previously. Here we
      modeled this hypothetical protein in order to contribute to the understanding of
      PD pathogenesis that should be served as an input in the future as drug targets.
      This study predicted a three-dimensional model of the complete sequence of
      hypothetical protein CAB55973.1 with a high value of identity and a good homology
      quality. Subcellular localization was found in the cytoplasm, mainly in the
      endosomal membrane. 36 protein-protein interactions related to PD were found. 11
      residues were predicted to interact with target proteins for ubiquitination.
      Binding site prediction showed that one domain (residues 163 to 238) might be
      involved in ubiquitination of target proteins. In this ubiquitin domain, residues
      were distributed similarly to those of the binding site of the ubiquitin
      interacting with the UIM of Hrs protein (PDB 2D3G). The hypothetical protein was
      constructed based on the complete sequence alignment, which allowed predicting
      the structure with a high accuracy. The functional prediction showed that only
      one domain of the hypothetical protein might be involved in the alpha- synuclein
      ubiquitination of the endosomal pathway of the PD.

PMID- 26201533
TI  - Structural and mechanical characterization of bioresorbable, elastomeric
      nanocomposites from poly(glycerol sebacate)/nanohydroxyapatite for tissue
      transport applications.
AB  - Poly(glycerol sebacate) (PGS)/nanohydroxyapatite (nHA) composites were assessed
      to develop new materials for closure via tissue transport for nonhealing defects
      (e.g., cleft palate and large skin wounds). The elastic shape memory polymer,
      PGS, was reinforced with nHA at 3 and 5% loading to increase the mechanical
      properties compared with the undoped PGS. Differential scanning calorimetry (DSC)
      was utilized to identify a glass transition temperature (Tg ) of -25 degrees C. X
      ray diffraction demonstrated a reduction in the amorphous nature of the material.
      The Fourier transform infrared photoacoustic spectral (FTIR-PAS) data showed
      decreased C?O bonding and increased hydrogen bonding with increased nHA
      incorporation. Composites exhibited Young's moduli in the range of 0.25-0.5 MPa
      and tensile strength of 1.5-3 N. No significant difference in extension to break
      (~50 mm) with addition of nHA was observed. The elastic modulus significantly
      increased for 5% PGS/nHA compared to 0 and 3% PGS/nHA and tensile strength
      significantly increased for 3% PGS/nHA compared to 0 and 5% PGS/nHA. Degradation
      of 5% nHA/PGS significantly increased during the second week compared to PGS 0
      and 3% PGS/nHA. The accelerated degradation for 5% PGS/nHA coupled with decreased
      flexibility and tensile strength implies an interruption in crosslinking. By
      maintaining flexibility and extension while increasing tensile strength, the 3%
      PGS/nHA doped satisfied the force range desired for closure of soft tissue
      defects. Based on this work, PGS with 3% nHA shape memory polymers should serve
      as a good candidate for closure of nonhealing soft tissues. (c) 2015 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1366-1373,
      2016.

PMID- 26201534
TI  - Postnatal growth failure in very low birthweight infants born between 2005 and
      2012.
AB  - BACKGROUND: Postnatal growth restriction is common in preterm infants and is
      associated with long-term neurodevelopmental impairment. Recent trends in
      postnatal growth restriction are unclear. METHODS: Birth and discharge weights
      from 25,899 Californian very low birthweight infants (birth weight 500-1500 g,
      gestational age 22-32 weeks) who were born between 2005 and 2012 were converted
      to age-specific Z-scores and analysed using multivariable modelling. RESULTS:
      Birthweight Z-score did not change between 2005 and 2012. However, the adjusted
      discharge weight Z-score increased significantly by 0.168 Z-scores (0.154, 0.182)
      over the study period, and the adjusted fall in weight Z-score between birth and
      discharge decreased significantly between those dates (by 0.016 Z-scores/year).
      The proportion of infants who were discharged home below the 10th weight-for-age
      centile or had a fall in weight Z-score between birth and discharge of >1
      decreased significantly over time. The comorbidities most associated with poorer
      postnatal growth were medical or surgical necrotising enterocolitis, isolated
      gastrointestinal perforation and severe retinopathy of prematurity, which were
      associated with an adjusted mean reduction in discharge weight Z-score of 0.24,
      0.57, 0.46 and 0.32, respectively. Chronic lung disease was not a risk factor
      after accounting for length of stay. CONCLUSIONS: Postnatal, but not prenatal,
      growth improved among very low birthweight infants between 2005 and 2012.
      Neonatal morbidities including necrotising enterocolitis, gastrointestinal
      perforations and severe retinopathy of prematurity have significant negative
      effects on postnatal growth.

PMID- 26201535
TI  - Congenital lacrimal fistula.

PMID- 26201537
TI  - Tandem electrochemical desalination-potentiometric nitrate sensing for seawater
      analysis.
AB  - We report on a methodology for the direct potentiometric determination of nitrate
      in seawater by in-line coupling to an electrochemical desalination module. A
      microfluidic custom-fabricated thin layer flat cell allows one to
      electrochemically reduce the chloride concentration of seawater more than 100
      fold, from 600 mM down to ~2.8 mM. The desalinator operates by the exhaustive
      electrochemical plating of the halides from the thin layer sample onto a silver
      element as silver chloride, which is coupled to the transfer of the counter
      cations across a permselective ion-exchange membrane to an outer solution. As a
      consequence of suppressing the major interference of an ion-exchanger based
      membrane, the 80 MUL desalinated sample plug is passed to a potentiometric flow
      cell of 13 MUL volume. The potentiometric sensor is composed of an all-solid
      state nitrate selective electrode based on lipophilic carbon nanotubes (f-MWCNTs)
      as an ion-to-electron transducer (slope of -58.9 mV dec(-1), limit of detection
      of 5 * 10(-7) M, and response time of 5 s in batch mode) and a miniaturized
      reference electrode. Nitrate is successfully determined in desalinated seawater
      using ion chromatography as the reference method. It is anticipated that this
      concept may form an attractive platform for in situ environmental analysis of a
      variety of ions that normally suffer from interference by the high saline level
      of seawater. 

PMID- 26201536
TI  - Blockade of interleukin-6 receptor enhances the anti-arthritic effect of
      glucocorticoids without decreasing bone mineral density in mice with collagen
      induced arthritis.
AB  - In a mouse arthritis model, we investigated whether interleukin-6 receptor (IL
      6R) blockade would enhance the anti-arthritic effect of glucocorticoids (GCs).
      DBA/1J mice were immunized with type II collagen (CII), and were treated with
      prednisolone (PSL) and/or anti-mouse IL-6R antibody (MR16-1). Also, the effects
      of IL-6 on gene expression and the nuclear translocation of glucocorticoid
      receptors (GRs) were examined in cultured cells treated with dexamethasone (DEX).
      PSL reduced the arthritis score dose-dependently in the collagen-induced
      arthritis (CIA) mouse model. The arthritis score in the PSL (3 mg/kg) + MR16-1
      group was lower than in the PSL (3 mg/kg) group, and at the same level as in the
      PSL (6 mg/kg) group. Lumbar vertebra bone mineral density (BMD) was decreased
      significantly in CIA mice and was higher in the PSL (3 mg/kg) + MR16-1 group than
      in the PSL (6 mg/kg) group. In the in-vitro synovial cells, IL-6 pretreatment
      attenuated the inhibitory effect of DEX on cyclooxygenase (COX)-2 expression and
      inhibited the nuclear translocation of GR induced by DEX. In contrast, in MC3T3
      E1 osteoblastic cells, IL-6 pretreatment exacerbated the decrease in expression
      of osteocalcin and the increase in expression of receptor activator of nuclear
      factor kappa-B ligand (RANKL) by DEX. We demonstrated that IL-6 signalling
      blockade by an anti-IL-6R antibody can augment the anti-arthritic effect of GCs
      and inhibit the bone loss they cause. 

PMID- 26201538
TI  - When are we operating for chronic rhinosinusitis? A systematic review of maximal
      medical therapy protocols prior to endoscopic sinus surgery.
AB  - BACKGROUND: Endoscopic sinus surgery (ESS) is considered a therapeutic option
      after failure of maximal medical therapy (MMT) for chronic rhinosinusitis (CRS).
      There is currently no consensus on the definition of MMT. The objective of this
      systematic review is to describe the various MMT criteria employed prior to
      considering ESS. METHODS: A systematic review was performed using the 2009
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines. Inclusion criteria were adults with CRS based on guideline diagnostic
      criteria, enrolled to undergo ESS, and study publication within the last 5 years
      (January 1, 2009, to December 30, 2014). Studies were excluded if the study
      population included non-CRS indications for ESS. Primary outcome was the MMT
      criteria employed prior to considering a patient a candidate for ESS. A subgroup
      analysis was performed based on polyp status. RESULTS: Of 387 reviewed studies,
      21% reported MMT criteria. When reported, criteria included topical nasal
      corticosteroids (91% of studies) for a mean of 8 +/- 8 weeks, oral antibiotics
      (89%) for 23 +/- 8 days, systemic corticosteroids (61%) for 18 +/- 12 days,
      saline irrigations (39%), oral antihistamines (11%), oral mucolytics (10%), and
      topical/oral decongestants (10%). CONCLUSION: A minority of studies report MMT
      criteria used as the indication for ESS. When reported, the majority included an
      8-week course of topical intranasal corticosteroids and 3-week course of oral
      antibiotics. Use of systemic corticosteroids did not differ based on polyp
      status. Because of variation in current MMT criteria, there is a need to develop
      standardized indications for ESS that will work to improve the appropriateness of
      care for patients with.

PMID- 26201539
TI  - Huaier aqueous extract inhibits cervical cancer cell proliferation via JNK/p38
      pathway.
AB  - Although the anticancer effects of Huaier extract have been widely investigated,
      including anti-proliferate, anti-angiogenic and anti-metastatic activities, the
      mechanisms are not well understood. This study aimed to elucidate the inhibitory
      effect of Huaier extract on tumor growth in cervical cancer cells and its
      molecular mechanisms. Cell viability and motility were measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony assays,
      migration, and invasive assays, respectively. The distribution of the cell cycle
      was analyzed by flow cytometry. Huaier inhibited cell viability of SiHa and C33A
      cells in a time- and dose-dependent manner; cell migration and invasiveness were
      also suppressed; Huaier was able to cause G2/M cell cycle arrest in C33A cells.
      The western blot results confirmed Huaier dose-dependently increased expression
      of phosphorylated c-Jun N-terminal kinase (JNK), p-38 and downregulated the
      expression of phosphorylated extracellular signal-regulated kinase (ERK) in a
      time- and dose-dependently manner. In vivo experiments showed that Huaier
      significantly suppressed the tumor volume of SiHa cell xenografts. These data
      suggest that Huaier may inhibit tumor proliferation in cervical cancer via the
      JNK/p38 signaling pathway. 

PMID- 26201541
TI  - Review of the endovascular approach to mitral valve disease.
AB  - The first interventional attempts at relieving mitral valve disease were in a
      sense minimally invasive, using relatively small incisions and introduction of
      instruments or a finger to open stenotic valves on the beating heart. The
      development of reliable cardiopulmonary bypass (CPB) made exact anatomic repair
      of mitral pathology possible with improved results. Mitral valve surgery on an
      arrested heart has been the mainstay of treatment for decades. Modifications and
      minimalization of the surgical approach using videoscopic or robotic instruments
      have made less invasive procedures possible. Such procedures demand excellent
      technical skills and are still not widely adopted. More recently, attempts have
      been made to repair mitral valves using endovascular access on the beating heart,
      guiding the repair process with real-time imaging. We are presenting a review of
      available and developing techniques for endovascular repair of the mitral valve.
      A device developed by our group will be briefly described. 

PMID- 26201540
TI  - Early life predictive markers of liver disease outcome in an International,
      Multicentre Cohort of children with Alagille syndrome.
AB  - BACKGROUND & AIMS: Liver disease in Alagille syndrome is highly variable. Many of
      the patients presenting with severe cholestasis early in life improve
      spontaneously; 10-20%, however, have progressive disease. It is currently not
      possible to predict long-term hepatic outcomes in Alagille syndrome. This
      international, multicentre study was aimed at identifying early life predictors
      of liver disease outcome. METHODS: Retrospective clinical, laboratory and
      radiographic data from a cohort of 144 Alagille syndrome patients, whose long
      term hepatic outcomes had been determined a priori based on previously published
      criteria, were collected. RESULTS: Sixty-seven patients had mild and 77 had
      severe hepatic outcome. Univariate analysis demonstrated that cholestasis and
      fibrosis on biopsy, as well as the presence of xanthomata were significantly
      different between the groups (P < 0.05 for all). Mixed model analysis revealed
      that total serum bilirubin and serum cholesterol were also associated with
      outcome (P = 0.001 and P = 0.002, respectively). Graphical representation of the
      data revealed a change in total bilirubin levels between 12 and 24 months of age
      in the mild group. Recursive partitioning identified a threshold for total
      bilirubin of 3.8 mg/dl (65 mmol/L) in that age-frame that differentiated between
      outcomes. A multivariable logistic regression model was developed using fibrosis,
      xanthomata and the total bilirubin cut-off of 3.8 mg/dl (65 mmol/L), which
      generated an area under the ROC curve of 0.792. CONCLUSIONS: The long-term
      hepatic outcomes of patients with Alagille syndrome can be predicted based on
      serum total bilirubin between the ages of 12-24 months combined with fibrosis on
      liver biopsy and the presence of xanthomata on physical examination.

PMID- 26201542
TI  - Long-term follow-up of laparoscopic transcutaneous inguinal herniorraphy with
      high transfixation suture ligature of the hernia sac.
AB  - BACKGROUND: Laparoscopic transcutaneous inguinal hernia repair in children may
      reduce postoperative pain, improve cosmesis, allow for less manipulation of the
      cord structures, and offer easy access to the contralateral groin. However, there
      is concern for unacceptably high recurrence rates when the procedure is
      generalized. To address this increase in recurrence, in 2011 we described in this
      journal a modification of the laparoscopic transcutaneous technique that
      replicates high transfixation ligature of the hernia sac with the aim of inducing
      more secure healing, preventing suture slippage, and distributing tension across
      two suture passes. We now describe our long-term follow-up of this novel repair.
      METHODS: After obtaining IRB approval, a retrospective chart review and phone
      follow-up were performed on all patients who underwent laparoscopic transfixation
      ligature hernia repair between October 2009 and August 2014 (including further
      follow-up of the 21 patients reviewed in the 2011 report of this technique). Data
      collection included demographics, laterality of hernia, evidence of recurrence,
      complications, and time to follow-up. RESULTS: Median follow-up was 24 months
      (range 2-52 months). Three pediatric surgeons performed 216 laparoscopic
      transfixation ligature repairs on 166 patients. DEMOGRAPHICS: mean age 29.5
      months (range 1-192 months); male 67.2% and female 32.8%; 4.2% of patients were
      premature at operation. Repairs were bilateral in 42% of patients, right sided in
      34%, and left sided in 24%. Three patients together experienced 4 recurrences,
      for an overall recurrence rate of 1.8%. Two of the recurrences occurred in a 2
      month old syndromic patient with severe congenital heart disease who recurred
      twice after laparoscopic transfixation ligature repair then subsequently failed
      an attempt at open repair. Excluding this one outlier patient, the recurrence
      rate was 0.9%. The complication rate was 1.7% (3 hydroceles and 1 inguinal
      hematoma; all resolved spontaneously). CONCLUSION: Laparoscopic high
      transfixation ligature hernia repair can be adopted by surgeons with basic
      laparoscopic skills, and result in excellent outcomes with acceptable recurrence
      rates.

PMID- 26201543
TI  - [Complication management for failed bone fracture healing: pseudarthrosis].
AB  - Delayed fracture healing for more than 6-8 months is defined as non-union
      (pseudarthrosis). Non-unions are classifiable as septic, aseptic, hypertrophic
      and atrophic non-unions. In case of septic non-unions the infection is treated
      primarily followed by treatment of the delayed fracture healing. Aseptic non
      unions may be treated non-operatively (e.g. shock wave therapy and/or ultrasound)
      or by various surgical strategies to stimulate bone regeneration and healing. 

PMID- 26201544
TI  - Screening for Lynch syndrome and referral to clinical genetics by selective
      mismatch repair protein immunohistochemistry testing: an audit and cost analysis.
AB  - Lynch syndrome (LS) accounts for around 3% of colorectal cancers (CRCs) and is
      caused by germline mutations in mismatch repair (MMR) genes. Recently, screening
      strategies to identify patients with LS have become popular. We audited CRCs
      screened with MMR immunohistochemistry (IHC) in 2013. 209 tumours had MMR IHC
      performed at a cost of L12 540. 47/209 (21%) cases showed IHC loss of expression
      in at least one MMR protein. 28/44 cases with loss of MLH1 had additional BRAF
      V600E testing, at a cost of L5040. MMR IHC reduced the number of potential
      clinical genetics referrals from 209 to 47. BRAF mutation testing, performed in a
      subset of cases with MLH1 loss, further reduced this to 21. At a cost of L1340
      per referral, this model of LS screening for clinical genetics referral had
      significant potential savings (L234 340) and can be easily implemented in
      parallel with MMR IHC done for prognostication in CRCs. 

PMID- 26201545
TI  - Extraneural hemangioblastoma of the kidney: the challenge for clinicopathological
      diagnosis.
AB  - BACKGROUND: Hemangioblastoma is a benign cerebellar tumour which may occur as a
      sporadic entity or in association with von Hippel-Lindau (VHL) disease in
      approximately 25% of cases. Renal hemangioblastoma (RH) is an extremely rare and
      newly recognised tumour. Here, we describe five cases of RH, one discovered by CT
      in an accident and the other four detected during routine examinations. METHODS:
      Five cases of renal hemangioblastoma retrieved from the Department of Pathology,
      Fudan University Shanghai Cancer Center were studied and the literatures were
      reviewed. Immunohistochemistry was used to differentiate and confirm this tumour.
      RESULTS: Pathological examination following tumour resection revealed RH in all
      cases, the first patient was also diagnosed with renal cell carcinoma (RCC),
      suggesting the possibility of VHL syndrome, but PCR sequencing analysis of the
      VHL gene confirmed no mutation in any of the three exons, implying sporadic
      disease. Histologically, the tumours were circumscribed, composed of sheets of
      oval or polygonal cells and a prominent vascular network. Tumour cells had
      pleomorphic nuclei, but mitotic figures were rare. The diagnosis of
      hemangioblastoma was confirmed by immunohistochemistry. CONCLUSIONS: RH is very
      rare and is challenging to differentially diagnose. Distinguishing RCC and RH is
      difficult and each has a different prognosis, so differentiating between them is
      essential for avoiding over-diagnosis and unnecessary treatment.

PMID- 26201546
TI  - Comprehensive technology-assisted training and supervision program to enhance
      depression management in primary care in Santiago, Chile: study protocol for a
      cluster randomized controlled trial.
AB  - BACKGROUND: Depression is a common and disabling condition. Since 2001, Chile has
      had a national program for depression in primary care and universal access to
      treatment for depressed people over the age of 15. There are National Guidelines
      to treat depression but no training program exists. The aim of the present study
      protocol is to measure the effectiveness of a comprehensive technology-assisted
      training and supervision program to enhance depression management in primary
      care. METHODS AND DESIGN: This is a two-arm, single-blind, cluster randomized
      controlled trial to compare the efficacy of the program versus usual care to
      treat depression in primary care clinics. In total, 434 depressed persons 18 to
      65 years of age, recruited from four primary care clinics located in Santiago,
      will participate in the study. DISCUSSION: In order to ensure the quality of
      interventions supported by the national program for depression in Chile, it is
      desirable to have training programs of proven effectiveness. TRIAL REGISTRATION:
      NCT02232854, registered on 2 September 2014.

PMID- 26201548
TI  - Hydrogen abstraction mechanisms and reaction rates of toluene+NO3.
AB  - The hydrogen abstraction reaction mechanisms of toluene molecule by NO3 radical
      were investigated theoretically with quantum chemistry and reaction kinetics. All
      the molecular structures, vibrational properties, and the intrinsic reaction
      coordinates were determined with B3LYP/6-311G(d,p). The non-dynamic electronic
      correlations were examined with the CASSCF dominant configurations. The energies
      and the potential energy profiles were refined with accurate model chemistry
      G3(MP2). Rate constants were determined using the CVT method over the temperature
      range 200-2000 K. It was found that in addition to the side chain H-abstraction,
      the ring H-abstraction reactions are also possible. The side chain H-abstraction
      rate constant is in very good agreement with the available experiments and has a
      non-Arrhenius characteristic. Nevertheless, all the ring H-abstractions follow
      the Arrhenius behavior well. The over-all reaction was found to have a complex
      reaction mechanism in which the side chain H-abstraction is dominant below 700 K
      while the ring H-abstractions are competitive above 800 K. The approximate
      apparent activation energies E app are 15.5 and 66.4 kJ mol(-1) at 300-700 K and
      800-2000 K, respectively. Graphical Abstract The calculation of the reaction rate
      indicates that the over-all reaction has a complex mechanism. The reaction
      proceeds mainly by the side chain H-abstraction at temperatures lower than 700 K
      and is nearly irreversible, while the competition of the ring H-abstractions
      becomes observable at higher temperatures and is reversible.

PMID- 26201547
TI  - Perception Versus Actual Performance in Timely Tissue Plasminogen Activation
      Administration in the Management of Acute Ischemic Stroke.
AB  - BACKGROUND: Timely thrombolytic therapy can improve stroke outcomes.
      Nevertheless, the ability of US hospitals to meet guidelines for intravenous
      tissue plasminogen activator (tPA) remains suboptimal. What is unclear is whether
      hospitals accurately perceive their rate of tPA "door-to-needle" (DTN) time
      within 60 minutes and how DTN rates compare across different hospitals. METHODS
      AND RESULTS: DTN performance was defined by the percentage of treated patients
      who received tPA within 60 minutes of arrival. Telephone surveys were obtained
      from staff at 141 Get With The Guidelines hospitals, representing top, middle,
      and low DTN performance. Less than one-third (29.1%) of staff accurately
      identified their DTN performance. Among middle- and low-performing hospitals
      (n=92), 56 sites (60.9%) overestimated their performance; 42% of middle
      performers and 85% of low performers overestimated their performance. Sites that
      overestimated tended to have lower annual volumes of tPA administration (median
      8.4 patients [25th to 75th percentile 5.9 to 11.8] versus 10.2 patients [25th to
      75th percentile 8.2 to 17.3], P=0.047), smaller percentages of eligible patients
      receiving tPA (84.7% versus 89.8%, P=0.008), and smaller percentages of DTN <=60
      minutes among treated patients (10.6% versus 16.6%, P=0.002). CONCLUSIONS:
      Hospitals often overestimate their ability to deliver timely tPA to treated
      patients. Our findings indicate the need to routinely provide comparative
      provider performance rates as a key step to improving the quality of acute stroke
      care.

PMID- 26201549
TI  - DFT study of the effects of interstitial impurities on the resistance of Cr-doped
      gamma-Fe(111) surface dissolution corrosion.
AB  - Using density-functional calculations, we studied the interaction between
      interstitial impurities (N, C) and gamma-Fe(111) surfaces doped, or not, with Cr,
      as well as the effect of Cr doping on the dissolution corrosion resistance of the
      gamma-Fe(111) surface. The elementary processes studied afforded microscopic
      insights into the formation of a Cr-depleted zone, a phenomenon that leads to
      local corrosion of the stainless steel surface. The aim of this work was to
      study, at the atomic scale, the effects of N and C on the segregation behavior of
      Cr and the synergetic effect between co-doped atoms on the resistance to
      dissolution corrosion of austenitic stainless steel surfaces. The results showed
      that interstitial impurities prefer to be trapped at near-surface sites, which
      can impact the segregation behavior of Cr such that it shifts from the surface to
      the subsurface. Electrode potential calculations and density of states analysis
      demonstrated that doping with Cr or inserting interstitial impurities into the
      solid solution can improve the surface corrosion resistance of an fcc Fe
      substrate, but detrimental effects on the surface corrosion resistance are
      induced by interactions between Cr and interstitial impurity atoms in co-doped
      surfaces. The formation of near-surface Cr carbides and nitrides (speculated to
      be Cr2N and Cr23C6 due to the results obtained for particular co-doped surfaces)
      was also noted. The results of our theoretical calculations explain some of the
      experimental results observed at the atomic scale. 

PMID- 26201550
TI  - Association of neuropsychiatric symptoms and sub-syndromes with cognitive
      impairment in community-dwelling Asian elderly.
AB  - OBJECTIVES: To investigate the presence of neuropsychiatric symptoms (NPS) and
      sub-syndromes in elderly community-dwelling Asians with varying severity of
      cognitive impairment. METHODS: Chinese and Malay participants (n = 613) from the
      Epidemiology of Dementia in Singapore (EDIS) Study aged >= 60 years underwent
      clinical examination, neuropsychological testing, and NPS assessment using the
      Neuropsychiatric Inventory (NPI). Diagnosis of no cognitive impairment (NCI),
      cognitive impairment-no dementia (CIND), including CIND-mild and CIND-moderate,
      and dementia were made using established criteria. RESULTS: A significant
      increase in the numbers of NPS was observed accompanying with increasing severity
      of cognitive impairment (p < 0.001). Compared to those with NCI/CIND-mild,
      participants with CIND-moderate [Odds ratio (OR): 4.2, 95% confidence interval
      (CI): 1.8-10.0] or dementia [OR: 9.2, 95% CI: 2.3-36.0] were more likely to have
      two or more neuropsychiatric sub-syndromes. Participants with CIND-moderate were
      more likely to have hyperactivity [OR: 2.0, 95% CI: 1.0-3.8] and apathy [OR: 2.9,
      95% CI: 1.0-8.4] sub-syndromes, whereas patients with dementia were more likely
      to have psychosis [OR: 6.9, 95% CI: 2.4-20.1], affective (OR: 8.7, 95% CI: 1.8
      42.9), and hyperactivity (OR: 5.4, 95% CI: 1.8-16.1). Furthermore, executive
      dysfunction and visual memory impairment were associated with the presence of
      three neuropsychiatric sub-syndromes; whist language and visuomotor speed
      impairment were related to the presence of two sub-syndromes. By contrast,
      impairment in attention, verbal memory, and visuoconstruction were not associated
      with any of the sub-syndromes. CONCLUSIONS: The presence of NPS and sub-syndromes
      increase with increasing severities of cognitive impairment, and different
      neuropsychiatric syndromes are associated with specific impairment on cognitive
      domains in community-dwelling Asian elderly.

PMID- 26201551
TI  - Decompressive hemicraniectomy in the management of acute stroke in children with
      Moyamoya disease: the difficult balance between the spontaneous postoperative
      revascularization process and the need for cranial reconstruction.
AB  - BACKGROUND AND IMPORTANCE: The decompressive hemicraniectomy (DCH) after
      malignant middle cerebral artery infarction in children is a rare procedure, and
      the indication is discussed as being controversial. Etiological Moyamoya disease
      has some additional challenges concerning the therapeutic strategy that have not
      mentioned in the recent literature, as it is dependent on special
      pathophysiology. CLINICAL PRESENTATION: We report a case of a four-year-old
      patient with a decompressive hemicraniectomy after malignant middle cerebral
      artery infarction on the right hemisphere based on a Moyamoya syndrome with
      proximal MCA occlusions on both sides. After the decompression there was a good
      restitution of the hemiparesis, aphasia, and consciousness loss on admission. The
      bone flap replacement is usually done after three month in our department to
      ensure brain swelling has subsided. In this patient the cranioplasty was not
      arranged because of the development of collateral vessels to the right motor
      region through the craniotomy defect, to protect the supply of the eloquent
      cortex. CONCLUSION: We conclude that the indication of DCH and postoperative
      treatment should be discussed individually, especially when neovascularisation
      developments can occur like in Moyamoya disease. An important point is the right
      timing for bone flap replacement, which should be directly after cerebral edema
      has subsided prior to the evolution of collaterals through the craniotomy defect.
      Additionally, leaving the opportunity for neovascularization through smaller
      defects has to be taken into account.

PMID- 26201552
TI  - Brain tumors in children with refractory seizures-a long-term follow-up study
      after epilepsy surgery.
AB  - PURPOSE: Epilepsy surgery is an established treatment option for medically
      refractory epilepsy. Brain tumors, besides dysplasias, vascular malformations,
      and other lesions, can cause refractory epilepsy. Long-term epilepsy-associated
      brain tumors, even though mostly benign, are neoplastic lesions and thus have to
      be considered as both epileptic and oncological lesions. METHODS: We
      retrospectively analyzed epileptological and oncological long-term follow-up (FU)
      in pediatric patients who underwent brain surgery for refractory epilepsy and
      whose histology showed a tumor as underlying cause (n = 107, mean FU 119 months).
      RESULTS: At last available outcome, 82.2% of patients were seizure free
      (International League Against Epilepsy (ILAE) class 1) and seizure outcome was
      stable over more than 14 years. Fifty-four percent of the patients were without
      anti-epileptic drugs (AEDs) at last available outcome; 96.2% of the tumors were
      classified WHO grade I and II and 3.7% were malignant (WHO grade III). Adjuvant
      treatment was administered in 5.7%; 2.9% had relapse and one patient died (tumor
      related mortality = 1.4%). After surgery, 91% of the patients attended regular
      school/university and/or professional training. CONCLUSIONS: This study shows
      that epileptological outcome within this group is promising and stable and
      oncological outcome has a very good prognosis. However, oncological FU must not
      be dismissed as a small percentage of patients who suffer from malignant tumors
      and adjuvant treatment, relapse, and mortality have to be considered.

PMID- 26201553
TI  - Cervical subluxation associated with posterior cervical hemivertebra.
AB  - PURPOSE: Hemivertebrae, associated with a failure in the formation and fusion of
      vertebral body ossification nuclei, are a common cause of thoracic or lumbar
      scoliosis. A cervical location is rare and even rarer as a cause of cervical
      subluxation in flexion and extension (for which only one previous case has been
      found). CASE REPORT: We report on the case of a 7-year-old female patient, who
      was examined for a cervical fusion defect, consisting of a posterior C4
      hemivertebra and a left hemiblock from C5 to C7. After performing surgery
      consisting of a C4 corpectomy and anterior fixation with intersomatic graft and
      plate, adequate cervical stabilization with only a self-limiting left C6
      brachialgia and ipsilateral Horner syndrome occurs in the postoperative period.
      CONCLUSION: Posterior cervical hemivertebra associated with instability is a very
      rare finding. The anterior approach with corpectomy and anterior plate enables
      suitable stabilization.

PMID- 26201554
TI  - Cerebrospinal fluid otorrhea and pseudomonal meningitis in a child with Mondini
      dysplasia: case report.
AB  - PURPOSE: Mondini dysplasia is a rare congenital inner ear malformation that
      presents with abnormal cochlear development with accompanied vestibular dilation
      and vestibular aqueduct enlargement. This dysfunctional anatomy provides the
      potential for sensorineural hearing deficits, cerebrospinal fluid leaks, and
      severe cases of recurrent meningitis. METHODS: We present the case of a child
      with Mondini dysplasia who presented with unilateral hearing loss and
      cerebrospinal fluid (CSF) otorrhea that was surgically repaired through a
      combined middle fossa/transmeatal middle ear approach to alleviate any recurrence
      of infection and cerebrospinal fluid otorrhea. RESULTS: Postoperatively, the
      patient remained neurologically stable without any further CSF leakage. CSF
      cultures revealed a Pseudomonas aeruginosa infection, a rare occurrence within
      the context of Mondini dysplasia. Retrograde bacterial spread from the external
      ear canal into the CSF space has been theorized as the possible pathogenesis of
      the resulting meningitis. The patient was successfully treated with intravenous
      antibiotics without any neurologic complications. CONCLUSIONS: Although Mondini
      dysplasia is a rare malformation, the life-threatening sequelae of meningitis
      that can result from the dysfunctional anatomy makes it a condition that requires
      elevated clinical vigilance, especially when considering children with hearing
      loss associated with recurrent meningitis, otorrhea, or rhinorrhea.

PMID- 26201555
TI  - Doctor-scientist-patients who barketh not: the quantified self-movement and crowd
      sourcing research.

PMID- 26201556
TI  - Is there a relationship between hepatitis B surface antibody status and diabetes?

PMID- 26201559
TI  - Timeless advice.

PMID- 26201560
TI  - Prepare farms for the future.

PMID- 26201558
TI  - Multiple B-cell epitope vaccine induces a Staphylococcus enterotoxin B-specific
      IgG1 protective response against MRSA infection.
AB  - No vaccine against methicillin-resistant Staphylococcus aureus (MRSA) has been
      currently approved for use in humans. Staphylococcus enterotoxin B (SEB) is one
      of the most potent MRSA exotoxins. In the present study, we evaluated the
      efficacy and immunologic mechanisms of an SEB multiple B-cell epitope vaccine
      against MRSA infection. Synthetic overlapping peptide ELISA identified three
      novel B-cell immunodominant SEB epitopes (in addition to those previously known):
      SEB31-48, SEB133-150, and SEB193-210. Six B-cell immunodominant epitopes (amino
      acid residues 31-48, 97-114, 133-150, 193-210, 205-222, and 247-261) were
      sufficient to induce robust IgG1/IgG2b-specific protective responses against MRSA
      infection. Therefore, we constructed a recombinant MRSA SEB-specific multiple B
      cell epitope vaccine Polypeptides by combining the six SEB immunodominant
      epitopes and demonstrated its ability to induce a robust SEB-specific IgG1
      response to MRSA, as well as a Th2-directing isotype response. Moreover,
      Polypeptides-induced antisera stimulated synergetic opsonophagocytosis killing of
      MRSA. Most importantly, Polypeptides was more effective at clearing the bacteria
      in MRSA-infected mice than the whole SEB antigen, and was able to successfully
      protect mice from infection by various clinical MRSA isolates. Altogether, these
      results support further evaluation of the SEB multiple B-cell epitope-vaccine to
      address MRSA infection in humans. 

PMID- 26201561
TI  - It's good to talk.

PMID- 26201562
TI  - Russia's crackdowns are jeopardizing its science.

PMID- 26201573
TI  - Vibrant Pluto stuns scientists.

PMID- 26201574
TI  - US tailored-medicine project aims for ethnic balance.

PMID- 26201575
TI  - French teenager healthy 12 years after ceasing HIV treatment.

PMID- 26201577
TI  - Iranian researchers welcome nuclear deal.

PMID- 26201576
TI  - Search for extraterrestrial intelligence gets a $100-million boost.

PMID- 26201578
TI  - UK shifts its space-science strategy.

PMID- 26201579
TI  - Quest for climate-proof farms.

PMID- 26201580
TI  - A cellular puzzle: The weird and wonderful architecture of RNA.

PMID- 26201581
TI  - Conservation: Stop misuse of biodiversity offsets.

PMID- 26201582
TI  - Environmental science: Agree on biodiversity metrics to track from space.

PMID- 26201587
TI  - Climate law: path paved for civil action.

PMID- 26201588
TI  - Climate law: Dutch decision raises bar.

PMID- 26201589
TI  - Hazardous products: Cut animal wastage in toxicology testing.

PMID- 26201590
TI  - Conservation management: Probe effects of krill fishing and climate.

PMID- 26201591
TI  - Trans-Pacific Partnership: Add conservation to US trade agreement.

PMID- 26201592
TI  - Nanotechnology: Pathfinder for DNA constructs.

PMID- 26201593
TI  - Computational imaging: Machine learning for 3D microscopy.

PMID- 26201594
TI  - Organic chemistry: Natural polarity inverted.

PMID- 26201595
TI  - Crystal structures of a polypeptide processing and secretion transporter.
AB  - Bacteria secrete peptides and proteins to communicate, to poison competitors, and
      to manipulate host cells. Among the various protein-translocation machineries,
      the peptidase-containing ATP-binding cassette transporters (PCATs) are
      appealingly simple. Each PCAT contains two peptidase domains that cleave the
      secretion signal from the substrate, two transmembrane domains that form a
      translocation pathway, and two nucleotide-binding domains that hydrolyse ATP. In
      Gram-positive bacteria, PCATs function both as maturation proteases and exporters
      for quorum-sensing or antimicrobial polypeptides. In Gram-negative bacteria,
      PCATs interact with two other membrane proteins to form the type 1 secretion
      system. Here we present crystal structures of PCAT1 from Clostridium thermocellum
      in two different conformations. These structures, accompanied by biochemical
      data, show that the translocation pathway is a large alpha-helical barrel
      sufficient to accommodate small folded proteins. ATP binding alternates access to
      the transmembrane pathway and also regulates the protease activity, thereby
      coupling substrate processing to translocation. 

PMID- 26201596
TI  - DNA rendering of polyhedral meshes at the nanoscale.
AB  - It was suggested more than thirty years ago that Watson-Crick base pairing might
      be used for the rational design of nanometre-scale structures from nucleic acids.
      Since then, and especially since the introduction of the origami technique, DNA
      nanotechnology has enabled increasingly more complex structures. But although
      general approaches for creating DNA origami polygonal meshes and design software
      are available, there are still important constraints arising from DNA geometry
      and sense/antisense pairing, necessitating some manual adjustment during the
      design process. Here we present a general method of folding arbitrary polygonal
      digital meshes in DNA that readily produces structures that would be very
      difficult to realize using previous approaches. The design process is highly
      automated, using a routeing algorithm based on graph theory and a relaxation
      simulation that traces scaffold strands through the target structures. Moreover,
      unlike conventional origami designs built from close-packed helices, our
      structures have a more open conformation with one helix per edge and are
      therefore stable under the ionic conditions usually used in biological assays. 

PMID- 26201597
TI  - Catalytic asymmetric umpolung reactions of imines.
AB  - The carbon-nitrogen double bonds in imines are fundamentally important functional
      groups in organic chemistry. This is largely due to the fact that imines act as
      electrophiles towards carbon nucleophiles in reactions that form carbon-carbon
      bonds, thereby serving as one of the most widely used precursors for the
      formation of amines in both synthetic and biosynthetic settings. If the carbon
      atom of the imine could be rendered electron-rich, the imine could react as a
      nucleophile instead of as an electrophile. Such a reversal in the electronic
      characteristics of the imine functionality would facilitate the development of
      new chemical transformations that convert imines into amines via carbon-carbon
      bond-forming reactions with carbon electrophiles, thereby creating new
      opportunities for the efficient synthesis of amines. The development of
      asymmetric umpolung reactions of imines (in which the imines act as nucleophiles)
      remains uncharted territory, in spite of the far-reaching impact such reactions
      would have in organic synthesis. Here we report the discovery and development of
      new chiral phase-transfer catalysts that promote the highly efficient asymmetric
      umpolung reactions of imines with the carbon electrophile enals. These catalysts
      mediate the deprotonation of imines and direct the 2-azaallyl anions thus formed
      to react with enals in a highly chemoselective, regioselective,
      diastereoselective and enantioselective fashion. The reaction tolerates a broad
      range of imines and enals, and can be carried out in high yield with as little as
      0.01 mole per cent catalyst with a moisture- and air-tolerant operational
      protocol. These umpolung reactions provide a conceptually new and practical
      approach to chiral amino compounds. 

PMID- 26201598
TI  - Statistical analysis of iron geochemical data suggests limited late Proterozoic
      oxygenation.
AB  - Sedimentary rocks deposited across the Proterozoic-Phanerozoic transition record
      extreme climate fluctuations, a potential rise in atmospheric oxygen or re
      organization of the seafloor redox landscape, and the initial diversification of
      animals. It is widely assumed that the inferred redox change facilitated the
      observed trends in biodiversity. Establishing this palaeoenvironmental context,
      however, requires that changes in marine redox structure be tracked by means of
      geochemical proxies and translated into estimates of atmospheric oxygen. Iron
      based proxies are among the most effective tools for tracking the redox chemistry
      of ancient oceans. These proxies are inherently local, but have global
      implications when analysed collectively and statistically. Here we analyse about
      4,700 iron-speciation measurements from shales 2,300 to 360 million years old.
      Our statistical analyses suggest that subsurface water masses in mid-Proterozoic
      oceans were predominantly anoxic and ferruginous (depleted in dissolved oxygen
      and iron-bearing), but with a tendency towards euxinia (sulfide-bearing) that is
      not observed in the Neoproterozoic era. Analyses further indicate that early
      animals did not experience appreciable benthic sulfide stress. Finally, unlike
      proxies based on redox-sensitive trace-metal abundances, iron geochemical data do
      not show a statistically significant change in oxygen content through the
      Ediacaran and Cambrian periods, sharply constraining the magnitude of the end
      Proterozoic oxygen increase. Indeed, this re-analysis of trace-metal data is
      consistent with oxygenation continuing well into the Palaeozoic era. Therefore,
      if changing redox conditions facilitated animal diversification, it did so
      through a limited rise in oxygen past critical functional and ecological
      thresholds, as is seen in modern oxygen minimum zone benthic animal communities. 

PMID- 26201601
TI  - Validation of Diagnoses of Transient Ischemic Attack in the Swedish Stroke
      Register (Riksstroke) TIA-Module.
AB  - BACKGROUND: In 2010, the Swedish Stroke Register (Riksstroke; RS) established a
      module for transient ischemic attacks (RS-TIA). We report a diagnostic validation
      study of patients included in RS-TIA. METHODS: During the first year, 7,825
      patients were registered at 59 out of 74 Swedish hospitals. A time-based TIA
      definition was applied. A sample of 180 patients (30 patients each from 6
      hospitals), with a similar distribution of age and sex as in RS-TIA, was
      prepared. Two independent observers assessed medical records for quality of
      documentation and assigned a diagnosis of likely, possible, unlikely TIA or
      ischemic stroke, according to prespecified criteria. RESULTS: The 2 observers
      agreed in 77% of cases that the event was a likely or possible TIA, in 3% that
      the event was an ischemic stroke, and in 2% that the event was an unlikely TIA.
      The observers disagreed in 8% of patients on TIA vs. ischemic stroke, and in 11%
      on a vascular vs. non-vascular cause. Quality of documentation was fair.
      CONCLUSIONS: There was interobserver agreement on diagnosis of TIA in the
      majority of patients included in RS-TIA. Diagnostic accuracy may be further
      improved by more systematic documentation of symptoms and signs.

PMID- 26201599
TI  - Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow
      engraftment.
AB  - Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used
      treatment for life-threatening conditions such as leukaemia; however, the
      molecular mechanisms regulating HSPC engraftment of the recipient niche remain
      incompletely understood. Here we develop a competitive HSPC transplant method in
      adult zebrafish, using in vivo imaging as a non-invasive readout. We use this
      system to conduct a chemical screen, and identify epoxyeicosatrienoic acids
      (EETs) as a family of lipids that enhance HSPC engraftment. The pro
      haematopoietic effects of EETs were conserved in the developing zebrafish embryo,
      where 11,12-EET promoted HSPC specification by activating a unique activator
      protein 1 (AP-1) and runx1 transcription program autonomous to the haemogenic
      endothelium. This effect required the activation of the phosphatidylinositol-3-OH
      kinase (PI(3)K) pathway, specifically PI(3)Kgamma. In adult HSPCs, 11,12-EET
      induced transcriptional programs, including AP-1 activation, which modulate
      several cellular processes, such as migration, to promote engraftment.
      Furthermore, we demonstrate that the EET effects on enhancing HSPC homing and
      engraftment are conserved in mammals. Our study establishes a new method to
      explore the molecular mechanisms of HSPC engraftment, and discovers a previously
      unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic
      generation and regeneration processes. EETs may have clinical application in
      marrow or cord blood transplantation. 

PMID- 26201602
TI  - Stability analysis of chemically modified mRNA using micropattern-based single
      cell arrays.
AB  - The measurement of mRNA turnover in living cells plays an important role in the
      search for stable mRNA constructs for RNA-based therapies. Here we show that
      automated time-lapse microscopy combined with micropatterned arrays allows for
      efficient high-throughput monitoring of fluorescent reporter protein expression
      at the single-cell level. The fluorescence time courses after mRNA transfection
      yield the distribution of individual mRNA expression and degradation rates within
      a population. We compare mRNA constructs with combinations of 5' and 3' UTR
      sequences and find a systematic broadening and shift towards longer functional
      half-lives for UTR stabilized mRNA. At the same time the life time distribution
      of the destabilized EGFP reporter protein was found to be constant and narrowly
      distributed. Using mathematical modeling, we show that mRNA functional life-time
      predicts the time-integrated protein level, i.e. the area under the curve (AUC)
      of mRNA translation. Our approach paves the way for quantitative assessment of
      hitherto unexplored mRNA functional life time heterogeneity, possibly predicated
      on multiple mRNA secondary structures and its dependence on UTR sequences. 

PMID- 26201603
TI  - Sequence variation in telomerase reverse transcriptase (TERT) as a determinant of
      risk of cardiovascular disease: the Atherosclerosis Risk in Communities (ARIC)
      study.
AB  - BACKGROUND: Telomerase reverse transcriptase (TERT) maintains telomere ends
      during DNA replication by catalyzing the addition of short telomere repeats. The
      expression of telomerase is normally repressed in somatic cells leading to a
      gradual shortening of telomeres and cellular senescence with aging.
      Interindividual variation in leukocyte telomere length has been previously
      associated with susceptibility to cardiovascular disease. The aim of the present
      study was to determine whether six variants in the TERT gene are associated with
      risk of incident coronary heart disease, incident ischemic stroke, and mortality
      in participants in the biracial population-based Atherosclerosis Risk in
      Communities (ARIC) study, including rs2736100 that was found to influence mean
      telomere length in a genome-wide analysis. METHODS: ARIC is a prospective study
      of the etiology and natural history of atherosclerosis in 15,792 individuals aged
      45 to 64 years at baseline in 1987-1989. Haplotype tagging SNPs in TERT were
      genotyped using a custom array containing nearly 49,000 SNPs in 2,100 genes
      associated with cardiovascular and metabolic phenotypes. Cox proportional hazards
      models were used to assess the association between the TERT polymorphisms and
      incident cardiovascular disease and mortality over a 20-year follow-up period in
      8,907 whites and 3,022 African-Americans with no history of disease at the
      baseline examination, while individuals with prevalent cardiovascular disease
      were not excluded from the analyses of mortality. RESULTS: After adjustment for
      age and gender, and assuming an additive genetic model, rs2736122 and rs2853668
      were nominally associated with incident coronary heart disease (hazards rate
      ratio = 1.20, p = 0.02, 95 % confidence interval = 1.03- 1.40) and stroke
      (hazards rate ratio = 1.17, p = 0.05, 95 % confidence interval = 1.00 - 1.38),
      respectively, in African-Americans. None of the variants was significantly
      associated with cardiovascular disease in white study participants or with
      mortality in either racial group. CONCLUSIONS: Replication in additional
      population-based samples combined with genotyping of polymorphisms in other genes
      involved in maintenance of telomere length may help to determine whether genetic
      variants associated with telomere homeostasis influence the risk of
      cardiovascular disease in middle-aged adults.

PMID- 26201604
TI  - Features of human scabies in resource-limited settings: the Cameroon case.
AB  - BACKGROUND: The persistent high prevalence of human scabies, especially in low-
      and middle-income countries prompted us to research the sociodemographic profile
      of patients suffering from it, and its spreading factors in Cameroon, a resource
      poor setting. METHODS: We conducted a cross-sectional survey from October 2011 to
      September 2012 in three hospitals located in Yaounde, Cameroon, and enrolled
      patients diagnosed with human scabies during dermatologists' consultations who
      volunteered to take part in the study. RESULTS: We included 255 patients of whom
      158 (62 %) were male. Age ranged from 0 to 80 years old with a median of 18
      (Inter quartile range: 3-29) years. One to eight persons of our patients'
      entourage exhibited pruritus (mean = 2.1 +/- 1.8). The number of persons per
      bed/room varied from 1 to 5 (mean = 2.1 +/- 0.8). The first dermatologist's
      consultation occurred 4 to 720 days after the onset of symptoms (mean = 77.1 +/-
      63.7). The post-scabies pruritus (10.2 % of cases) was unrelated to the
      complications observed before correct treatment (all p values > 0.05), mainly
      impetiginization (7.1 %) and eczematization (5.9 %). CONCLUSION: Human scabies
      remains preponderant in our milieu. Populations should be educated on preventive
      measures in order to avoid this disease, and clinicians' knowledges must be
      strengthened for its proper diagnosis and management.

PMID- 26201605
TI  - Complex Therapeutical Approaches to Complex Diseases.

PMID- 26201608
TI  - Getting an Insight into the Complexity of Major Chronic Inflammatory and
      Degenerative Diseases: A Potential New Systemic Approach to Their Treatment.
AB  - As the modern society is troubled by multi-factorial diseases, research has been
      conducted on complex realities including chronic inflammation, cancer, obesity,
      HIV infection, metabolic syndrome and its detrimental cardiovascular
      complications as well as depression and other brain disorders. Deterioration of
      crucial homeostatic mechanisms in such diseases invariably results in activation
      of inflammatory mediators, chronic inflammation, loss in immunological function,
      increased susceptibility to diseases, alteration of metabolism, decrease of
      energy production and neuro-cognitive decline. Regulation of genes expression by
      epigenetic code is the dominant mechanism for the transduction of environmental
      inputs, such as stress and inflammation to lasting physiological changes. Acute
      and chronic stress determines DNA methylation and histone modifications in brain
      regions which may contribute to neuro-degenerative disorders. Nuclear
      glucocorticoids receptor interacts with the epigenoma resulting in a cortisol
      resistance status associated with a deterioration of the metabolic and immune
      functions. Gonadal steroids receptors have a similar capacity to produce
      epigenomic reorganization of chromatine structure. Epigenomic-induced reduction
      in immune cells telomeres length has been observed in many degenerative diseases,
      including all types of cancer. The final result of these epigenetic alterations
      is a serious damage to the neuro-endocrine-immune-metabolic adaptive systems. In
      this study, we propose a treatment with stem cells differentiation stage factors
      taken from zebrafish embryos which are able to regulate the genes expression of
      normal and pathological stem cells in a different specific way. 

PMID- 26201607
TI  - Stem Cell Differentiation Stage Factors from Zebrafish Embryo: A Novel Strategy
      to Modulate the Fate of Normal and Pathological Human (Stem) Cells.
AB  - In spite of the growing body of evidence on the biology of the Zebrafish embryo
      and stem cells, including the use of Stem Cell Differentiation Stage Factors
      (SCDSFs) taken from Zebrafish embryo to impact cancer cell dynamics,
      comparatively little is known about the possibility to use these factors to
      modulate the homeostasis of normal human stem cells or to modulate the behavior
      of cells involved in different pathological conditions. In the present review we
      recall in a synthetic way the most important researches about the use of SCDSFs
      in reprogramming cancer cells and in modulating the high speed of multiplication
      of keratinocytes which is characteristic of some pathological diseases like
      psoriasis. Moreover we add here the results about the capability of SCDSFs in
      modulating the homeostasis of human adiposederived stem cells (hASCs) isolated
      from a fat tissue obtained with a novel-non enzymatic method and device. In
      addition we report the data not yet published about a first protein analysis of
      the SCDSFs and about their role in a pathological condition like
      neurodegeneration. 

PMID- 26201606
TI  - Treatment of Pancreatic Cancer with Pharmacological Ascorbate.
AB  - The prognosis for patients diagnosed with pancreatic cancer remains dismal, with
      less than 3% survival at 5 years. Recent studies have demonstrated that high
      dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces
      cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs.
      normal cells, suggesting a promising new role of ascorbate as a therapeutic
      agent. At physiologic concentrations, ascorbate functions as a reducing agent and
      antioxidant. However, when pharmacological ascorbate is given intravenously, it
      is possible to achieve millimolar plasma concentration. At these pharmacological
      levels, and in the presence of catalytic metal ions, ascorbate can induce
      oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in
      vitro and in vivo studies have demonstrated ascorbate oxidation occurs
      extracellularly, generating H2O2 flux into cells resulting in oxidative stress.
      Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts
      and displays synergistic cytotoxic effects when combined with gemcitabine in
      pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic
      cancer patients have demonstrated safety and potential efficacy. In this chapter,
      we will review the mechanism of ascorbate-induced cytotoxicity, examine the use
      of pharmacological ascorbate in treatment and assess the current data supporting
      its potential as an adjuvant in pancreatic cancer. 

PMID- 26201609
TI  - The PI3K-AKt-mTOR Pathway and New Tools to Prevent Acquired Hormone Resistance in
      Breast Cancer.
AB  - Acquired hormone resistance is an old hurdle and still represents to be a
      constant challenge in oncology for the medical community. Most recently, mainly
      following the results of BOLERO-2 study, the activation of the PI3K-AKT-mTOR
      pathway is considered clinically relevant for tumor escape from hormone
      dependence in breast cancer. In the BOLERO-2 trial, a combination of everolimus,
      mTOR inhibitor, and exemestane significantly prolonged the median progression
      free survival (PFS) compared to exemestane alone in advanced breast cancer
      patients with acquired endocrine resistance. Therefore, the inhibitors of the
      PI3K-AKT-mTOR pathway are a new class of drugs in great expansion joined with
      great expectation. This review article focuses on this special issue and briefly
      reports on the results of clinical trials using PI3K-AKT-mTOR inhibitors.
      However, the emergence of resistance to this new class of drugs, evidenced by the
      basic research and the relatively less benefit shown in the clinical trials, has
      been emerging as a new undesirable complication. Therefore, the principal
      elucidated mechanisms of the resistance to the inhibitors of the PI3K-AKT-mTOR
      pathway and the related potential therapeutic strategies are described. A more
      general immunological approach to delay acquired hormone resistance has also been
      considered and commented upon. 

PMID- 26201610
TI  - Changing the paradigm of organ utilization from PHS increased-risk donors: an
      opportunity whose time has come?
AB  - Approximately 8-11% of all organ donors are classified by Public Health Service
      (PHS) as increased-risk. The proportion of PHS increased-risk donors is on the
      rise. At the University of Washington Medical Center, in 2014, the proportion of
      transplants from PHS increased-risk donors was 28% of liver transplants and 23%
      of kidney transplants. Nationally, transplant providers have been reluctant to
      use organs from PHS increased-risk donors because of concern for transmission of
      HIV, HCV, or HBV. There is also patient apprehension when these organs are being
      offered, and thus the discard rate of these otherwise good quality organs is
      high. Because of the organ shortage, preventing underutilization of such organs
      is essential. We provide data and considerations that should be used to guide the
      use of organs from PHS increased-risk donors. 

PMID- 26201611
TI  - Hypoxia-induced autophagy mediates cisplatin resistance in lung cancer cells.
AB  - Hypoxia which commonly exists in solid tumors, leads to cancer cells
      chemoresistance via provoking adaptive responses including autophagy. Therefore,
      we sought to evaluate the role of autophagy and hypoxia as well as the underlying
      mechanism in the cisplatin resistance of lung cancer cells. Our study
      demonstrated that hypoxia significantly protected A549 and SPC-A1 cells from
      cisplatin-induced cell death in a Hif-1alpha- and Hif-2alpha-dependent manner.
      Moreover, compared with normoxia, cisplatin-induced apoptosis under hypoxia was
      markedly reduced. However, when autophagy was inhibited by 3-MA or siRNA targeted
      ATG5, this reduction was effectively attenuated, which means autophagy mediates
      cisplatin resisitance under hypoxia. In parallel, we showed that hypoxia robustly
      augmented cisplatin-induced autophagy activation, accompanying by suppressing
      cisplatin-induced BNIP3 death pathways, which was due to the more efficient
      autophagic process under hypoxia. Consequently, we proposed that autophagy was a
      protective mechanism after cisplatin incubation under both normoxia and hypoxia.
      However, under normoxia, autophagy activation 'was unable to counteract the
      stress induced by cisplatin, therefore resulting in cell death, whereas under
      hypoxia, autophagy induction was augmented that solved the cisplatin-induced
      stress, allowing the cells to survival. In conclusion, augmented induction of
      autophagy by hypoxia decreased lung cancer cells susceptibility to cisplatin
      induced apoptosis.

PMID- 26201612
TI  - The Envelope of Physiological Motion of the First Carpometacarpal Joint.
AB  - Much of the hand's functional capacity is due to the versatility of the motions
      at the thumb carpometacarpal (CMC) joint, which are presently incompletely
      defined. The aim of this study was to develop a mathematical model to completely
      describe the envelope of physiological motion of the thumb CMC joint and then to
      examine if there were differences in the kinematic envelope between women and
      men. In vivo kinematics of the first metacarpal with respect to the trapezium
      were computed from computed tomography (CT) volume images of 44 subjects (20M,
      24F, 40.3 +/- 17.7 yr) with no signs of CMC joint pathology. Kinematics of the
      first metacarpal were described with respect to the trapezium using helical axis
      of motion (HAM) variables and then modeled with discrete Fourier analysis. Each
      HAM variable was fit in a cyclic domain as a function of screw axis orientation
      in the trapezial articular plane; the RMSE of the fits was 14.5 deg, 1.4 mm, and
      0.8 mm for the elevation, location, and translation, respectively. After
      normalizing for the larger bone size in men, no differences in the kinematic
      variables between sexes could be identified. Analysis of the kinematic data also
      revealed notable coupling of the primary rotations of the thumb with translation
      and internal and external rotations. This study advances our basic understanding
      of thumb CMC joint function and provides a complete description of the CMC joint
      for incorporation into future models of hand function. From a clinical
      perspective, our findings provide a basis for evaluating CMC pathology,
      especially the mechanically mediated aspects of osteoarthritis (OA), and should
      be used to inform artificial joint design, where accurate replication of
      kinematics is essential for long-term success. 

PMID- 26201613
TI  - Lipoprotein-apheresis: Austrian consensus on indication and performance of
      treatment.
AB  - The prevalence of familial disorders of lipid metabolism in Europe is higher than
      believed so far. In severely affected patients in whom conventional combined
      lipid lowering agents are insufficient to achieve target values, patients being
      intolerant to all the available members of the statin family as well as in
      patients with elevated lipoprotein(a) (100 mg/dl) and progression of
      atherosclerotic vascular disease, despite even normal low-density lipoproteins
      (LDL)-cholesterol values, lipoprotein-apheresis treatment is indicated. The
      Austrian Apheresis Consensus compares the inclusion criteria for patients to be
      treated in Austria with those from Italy, Germany, Spain, Japan, UK and the
      United States. The cut off level of 100 mg/dl for lipoprotein(a) is higher in
      Austria as compared to the aforementioned countries (50 or 60 mg/dl,
      respectively). The available clinical data reveal that regular weekly lipoprotein
      apheresis not only results in a significant lowering of the respective
      atherogenic lipid and lipoprotein parameters, but also in a significant decrease
      in clinical events and interventions. The underlying mechanisms such as non-lipid
      effects, side effects as well as the different available treatment principles are
      compared. For patients meeting the inclusion criteria, lipoprotein apheresis is a
      safe and effective therapy significantly reducing vascular events.

PMID- 26201614
TI  - Role of TRPV1 and ASIC3 channels in experimental occlusal interference-induced
      hyperalgesia in rat masseter muscle.
AB  - BACKGROUND: Masticatory muscle pain may occur following immediate occlusal
      alteration by dental treatment. The underlying mechanisms are poorly understood.
      Transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channel-3
      (ASIC3) mediate muscle hyperalgesia under various pathologic conditions. We have
      developed a rat model of experimental occlusal interference (EOI) that
      consistently induces mechanical hyperalgesia in jaw muscles. Whether TRPV1 and
      ASIC3 mediate this EOI-induced hyperalgesia is unknown. METHODS: Rat model of EOI
      induced masseter hyperalgesia was established. Real-time polymerase chain
      reaction, Western blot and retrograde labelling combined with immunofluorescence
      were performed to evaluate the modulation of TRPV1 and ASIC3 expression in
      trigeminal ganglia (TGs) and masseter afferents of rats after EOI. The effects of
      intramuscular administration of TRPV1 and ASIC3 antagonists on the EOI-induced
      hyperalgesia in masseter muscle were examined. RESULTS: After EOI, gene
      expressions and protein levels of TRPV1 and ASIC3 in bilateral TGs were up
      regulated. The percentage of ASIC3- (but not TRPV1-) positive neurons in masseter
      afferents increased after EOI. More small-sized and small to medium-sized
      masseter afferents expressed TRPV1 and ASIC3 separately following EOI. These
      changes peaked at day 7 and then returned to original status within 10 days after
      EOI. Intramuscular administration of the TRPV1 antagonist AMG-9810 partially
      reversed this mechanical hyperalgesia in masseter muscle. No improvement was
      exhibited after administration of the ASIC3 antagonist APETx2. Co-injection of
      AMG-9810 and APETx2 enhanced the effect of AMG-9810 administration alone.
      CONCLUSIONS: Peripheral TRPV1 and ASIC3 contribute to the development of the EOI
      induced mechanical hyperalgesia in masseter muscle.

PMID- 26201615
TI  - Serotonergic dysfunction in the A53T alpha-synuclein mouse model of Parkinson's
      disease.
AB  - Parkinson's disease, neuropathologically defined by the aggregation of alpha
      synuclein, is characterized by neuropsychiatric symptoms such as depression and
      anxiety preceding the onset of motor symptoms. A loss of serotonergic neurons or
      their projections into the hippocampus and alterations in serotonin release may
      be linked to these symptoms. Here, we investigate the effect of human A53T alpha
      synuclein on serotonergic neurons using 12-months-old transgenic mice. We
      detected human alpha-synuclein in the perikarya of brainstem median and dorsal
      raphe neurons as well as in serotonergic fibers in the hippocampus. Despite
      intracellular alpha-synuclein accumulation there was no loss of serotonergic
      neurons in dorsal and median raphe nuclei of A53T alpha-synuclein mice. However,
      serotonin levels were significantly reduced in the brainstem. In addition,
      serotonergic fiber density in the dorsal dentate gyrus was significantly less
      dense in transgenic mice. Interestingly, we detected a significantly compromised
      increase in doublecortin+ neuroblasts after chronic treatment with fluoxetine at
      the site of reduced serotonergic innervation, the infrapyramidal blade of the
      dorsal dentate gyrus in A53T alpha-synuclein mice. This suggests that alpha
      synuclein affects serotonergic projections in a spatially distinct pattern within
      the hippocampus thereby influencing the response to antidepressant treatment.

PMID- 26201616
TI  - Hepatic fibrosis developing in morbid obesity independent of steatohepatitis: new
      mechanism or the Rube Goldberg machine?

PMID- 26201617
TI  - Angiogenesis: a phenomenon which aggravates chronic liver disease progression.
AB  - It has become increasingly clear that angiogenesis occurring during chronic wound
      healing and fibrogenesis provides a key contribution to disease progression and
      complications. The association of fibrogenesis and angiogenesis should be
      regarded as crucial in the modern evaluation of liver disease progression and in
      the search for therapeutic targets. Physiological hepatic angiogenesis occurs
      during liver regeneration, contributing to the formation of new functional
      sinusoids. Pathological angiogenesis in liver is characterized by intrahepatic
      vascular remodeling with capillarization of the sinusoids and development of
      intrahepatic shunts, which lead to increased hepatic resistance and decreased
      effective hepatocyte perfusion. The problem of angiogenesis in chronic hepatitis
      C and nonalcoholic fatty liver disease has not been fully resolved. This
      manuscript briefly describes pathogenesis of new blood vessel formation in
      chronic hepatitis and potential role of angiogenesis in disease progression. 

PMID- 26201618
TI  - Are we ready to use the hepatitis B surface antigen level to guide peginterferon
      treatment in HBeAg-negative chronic hepatitis B?

PMID- 26201619
TI  - Hepatitis C infection and chronic renal diseases.
AB  - Hepatitis C virus (HCV) infection and chronic renal diseases can be linked in two
      different ways. Some forms of renal disease are precipitated by HCV infection,
      while patients with end-stage renal disease are at increased risk for acquiring
      HCV infection. Patients with chronic HCV infection and renal disease have a poor
      prognosis. Most studies on treatment of HCV and renal diseases have been
      uncontrolled trials with small number of subjects. So, there is a lack of
      evidence-based recommendations and guidelines on the management of this
      condition. In this review, we will attempt to provide the most recent insights on
      HCV infection both as a extrahepatic manifestations and as a complication of end
      stage renal patients. 

PMID- 26201620
TI  - Etiopathogenesis of primary biliary cirrhosis: an overview of recent
      developments.
AB  - Substantial advancements in the field of primary biliary cirrhosis (PBC) research
      have broadened our understanding of this enigmatic disease. Genome-wide studies
      have identified several new candidate genes involved in the immunoregulatory
      process, particularly those responsible for antigen presentation and lymphocyte
      signaling. Examples include the HLA class-II region and genes implicated in IL12
      JAK/STAT signaling, and the NF-kappaB and TNF signaling pathways. Environmental
      triggers appear to disrupt the pre-existing, unstable immune tolerance in
      genetically susceptible individuals, and molecular mimics of the PBC-specific
      autoantigen (PDC) may be derived from microbes or xenobiotic compounds, which
      modify native proteins, making them immunogenic. Although the vast majority of
      patients with PBC are AMA-positive, a variety of disease-specific antinuclear
      antibodies have been recognized in conferring a worse clinical outcome. There has
      also been a revived interest in the role of antibody-secreting B cells in murine
      models suggesting that depletion of these cells paradoxically exacerbates
      cholangiopathy. Biliary specificity in PBC is most likely driven by the
      uniqueness of cholangiocyte apoptosis in which the PDC-E2 autoantigen undergoes
      differential glutathiolation. Cholangiocytes also possess the ability to
      phagocytose neighboring apoptotic cells, present intact immunoreactive antigen,
      and undergo attack from autoantibodies, the innate immune system, and
      autoreactive lymphocytes. Cellular senescence and a lack of functioning T
      regulatory cells are proposed mechanisms by which this multi-lineage process is
      thought to be enhanced. This review summarizes these key advances as the true
      complexities of the disease process begin to be unraveled. 

PMID- 26201621
TI  - Adenoviral gene therapy in hepatocellular carcinoma: a review.
AB  - BACKGROUND: Hepatocellular carcinoma is the third leading cause of cancer death.
      Single or multiple mutations in genes related to growth control, apoptosis,
      invasion and metastasis have been determined; so a better understanding of the
      molecular genetic basis of malignant transformation, tumor progression and host
      interaction has led to significant progress in the development of new therapeutic
      agents. The ability of adenovirus vectors to deliver and express genes at high
      yields in HCC treatment has been demonstrated and well documented over the last
      few years. OBJECTIVE: To overview and provide an update of what has been
      accomplished in the field of adenoviral gene therapy and its application in
      hepatocellular carcinoma treatment. METHODS: Original articles were searched
      using Pubmed and other medical databases to get the most representative and
      actual information to establish the current state of the investigation of Ad
      vectors in HCC. RESULTS: Good results have been accomplished in preclinical
      models using new Ad vectors and especially AAV vectors, it is important to
      motivate further clinical trials to corroborate all the experience obtained.
      CONCLUSIONS: Ad and AAV must be considered as an opportunity to improve the
      quality of life and survival of HCC patients.

PMID- 26201622
TI  - Epidemiology of a fast emerging disease in the Asia-Pacific region: non-alcoholic
      fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is rapidly increasing in the Asia
      Pacific and affects up to 30 % of the general population. In younger children,
      prevalence has been reported to be between 2.1 and 4.5 %. The prevalence of NAFLD
      increases with increasing age. NAFLD is more prevalent in men than women, but
      this trend fades in older age group. NAFLD is one of the most common causes of
      raised serum ALT levels and the latter is closely related to the presence of
      features of metabolic syndrome. NAFLD may contribute to metabolic syndrome in a
      similar way as visceral adiposity and can be an early predictor of metabolic
      disorders. NAFLD increases the risk of developing diabetes mellitus and is
      closely related to degree of glucose intolerance. A significant proportion of
      patients with NAFLD have impaired glucose tolerance or diabetes mellitus but with
      normal fasting blood glucose, highlighting the importance of oral glucose
      tolerance test in NAFLD patients with normal fasting blood glucose. Besides liver
      related complications, NAFLD has been associated with cardiovascular
      complications, hyperuricemia, gout, chronic kidney disease, gallstone disease,
      colorectal adenomatous polyp, and polycystic ovarian syndrome. NAFLD seems to be
      related to host metabolic factors rather than viral factors and does not seem to
      affect severity of the liver disease in patients with chronic hepatitis B. On the
      other hand, hepatic steatosis may be related to both host metabolic and viral
      factors in patients with chronic hepatitis C and seems to adversely impact on the
      severity of liver disease and possibly response to antiviral therapy. 

PMID- 26201623
TI  - The new epidemiology of nosocomial bacterial infections in cirrhosis:
      therapeutical implications.
AB  - Cirrhotic patients are at increased risk of developing infection, sepsis and
      death. Enterobacteriaceae and nonenterococcal streptococci are the main bacteria
      responsible for spontaneous and urinary infections in this population. Prompt and
      appropriate treatment is basic in the management of cirrhotic patients with
      infection. Third-generation cephalosporins continue to be the gold-standard
      antibiotic treatment of the majority of infections acquired in the community
      because responsible strains are usually susceptible to beta-lactams. By contrary,
      nosocomial infections are nowadays frequently caused by multiresistant bacteria
      (extended-spectrum beta-lactamase-producing Enterobacteriaceae, Pseudomonas
      aeruginosa, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant
      enterococci among others) that are nonsusceptible to the main antibiotics.
      Treatment of these infections requires the use of broader spectrum antibiotics
      (carbapenems) or of antibiotics that are active against specific resistant
      bacteria (glycopeptides, linezolid, daptomycin, amikacin and colistin). Empirical
      antibiotic schedules must be adapted to the local epidemiological pattern of
      antibiotic resistance. Careful restriction of antibiotic prophylaxis to the high
      risk population is also mandatory to reduce the spread of multiresistant bacteria
      in cirrhosis. 

PMID- 26201624
TI  - Paradigms in the management of hepatic hydrothorax: past, present, and future.
AB  - Hepatic hydrothorax (HH) is an infrequent but a well-known complication of portal
      hypertension in patients with end-stage liver disease. The estimated prevalence
      of HH is around 4-6 % in cirrhotics. Thoracentesis and pleural fluid analysis is
      a must for establishing the diagnosis of this transudative effusion in the
      absence of primary cardiopulmonary disease. Management strategies include sodium
      restriction, diuretics, thoracentesis, transjugular intrahepatic portosystemic
      shunt, pleurodesis, and video assisted thoracic surgery in selected patients.
      Liver transplantation remains the ultimate definitive management paradigm.
      Refractory HH thus warrants prompt consideration of liver transplantation. 

PMID- 26201625
TI  - A comparison of clevudine and entecavir for treatment-naive patients with chronic
      hepatitis B: results after 2 years of treatment.
AB  - BACKGROUND: This study was undertaken to compare the efficacy, safety, and
      resistance profile of clevudine (CLV) and entecavir (ETV) following a 2-year
      treatment period. METHODS: One hundred and eight Korean patients from the prior
      48-week study were followed with continuous therapy for up to 2 years and
      monitored for hepatitis B virus (HBV) DNA levels, HBeAg seroconversion, serum
      ALT, emergence of drug-resistant mutant HBV, and drug-related adverse events.
      RESULTS: A complete virological response during the 2-year treatment period
      occurred in 68.0 % in the CLV group and in 84.5 % in the ETV group (p = 0.043).
      The cumulative percentage of patients with sustained virological responses at 2
      years was 54.0 and 77.6 % in the CLV and ETV group, respectively (p = 0.010).
      Virological breakthrough occurred in 12 patients in the CLV group; however, there
      were none in the ETV group (p < 0.001). HBeAg seroconversion rates were not
      different between the two groups. In patients who maintained sustained
      virological responses at 2 years, the mean reduction in HBsAg titer was -0.24 and
      -0.06 log IU/ml in the CLV and ETV group, respectively (p > 0.05). Clinical
      myopathy occurred in seven patients in the CLV group; however, this was not
      observed in the ETV group (p = 0.004). CONCLUSIONS: ETV was associated with a
      significantly higher virological response rate than CLV at 2 years. ETV was
      superior to CLV in terms of the drug resistance profile and the development of
      clinical myopathy. Further studies to see whether the unique characteristic of
      CLV to reduce HBsAg titer is associated with the removal of ccc-DNA from
      hepatocytes and the remission of the disease are needed.

PMID- 26201626
TI  - Short hairpin RNAs with a 2- or 3-base mismatch inhibit HBV expression and
      replication in HepG2 cells.
AB  - PURPOSE: To assess the functions of mismatched short hairpin RNAs (shRNAs) that
      inhibit replication and the expression of hepatitis B virus (HBV), two shRNAs
      possessing a 2- or 3-base mismatch that targeted HBV were studied. METHODS:
      shRNAs and pHY106-HBV were cotransfected into HepG2 cells. The culture
      supernatants were collected and used in hepatitis B surface antigen (HBsAg) and
      hepatitis B e antigen (HBeAg) assays. The levels of HBsAg and HBcAg mRNA were
      detected by reverse-transcriptase PCR (RT-PCR). HBV DNA replication intermediates
      were extracted for Southern blot hybridization. RESULTS: The results demonstrate
      that mismatched shRNA-458 and shRNA-635 can significantly inhibit HBsAg and HBeAg
      protein expression, and the maximal inhibition ratio for both proteins was found
      at 72 h after cotransfection: 80 and 50 %, respectively. Similar inhibitory
      effects were found on HBsAg and HBcAg mRNA levels and HBV DNA replication
      intermediates at 72 h after cotransfection, and the inhibition ratio was found to
      be approximately 70 and 90 %, respectively. CONCLUSIONS: Despite the 2- or 3-base
      mismatch between the shRNAs and the HBV target sequences, shRNA-458 and shRNA-635
      exerted a significant inhibitory effect on HBsAg and HBeAg expression and HBV
      replication. This indicates that mismatched shRNAs could be a promising therapy
      for HBV.

PMID- 26201627
TI  - Analysis of discordance between transient elastography and liver biopsy for
      assessing liver fibrosis in chronic hepatitis B virus infection.
AB  - BACKGROUND: Transient elastography (TE) is used to assess liver fibrosis in
      chronic hepatitis B virus (CHBV) infection. However, factors affecting liver
      stiffness (LS) values and discordance between TE and liver biopsy in CHBV
      infection remain to be evaluated. AIM: The aim is to define the optimal cutoff
      values of LS for significant fibrosis (>=F2) and cirrhosis (F4) and to study the
      clinical and histological variables associated with LS values and discordance
      between TE and liver biopsy in assessing liver fibrosis in CHBV-infected
      subjects. METHODS: Patients with CHBV infection (n = 200; 159 male; age 37.6 +/-
      3.7 years) underwent liver biopsy concomitantly with TE. Liver biopsy was scored
      for activity (Ishak score), fibrosis (METAVIR score), steatosis, cholestasis, and
      congestion. Hepatic fibrosis percentage was estimated by morphometry. RESULTS:
      Liver stiffness values were significantly correlated with histological activity
      index (HAI) score, F score, and fibrosis percentage. Optimal cutoff values for
      prediction of significant fibrosis and cirrhosis were 7.05 kPa [sensitivity 81.2
      %; specificity 74 %; area under the receiver operating characteristic curve
      (AUROC) 0.850] and 10.85 kPa (sensitivity 87 %; specificity 85.3 %; AUROC 0.907),
      respectively. A total of 47 (23.5 %) [overestimation of actual fibrosis by TE, 34
      (17 %); underestimation, 13 (6.5 %)] and 28 (14 %) [overestimation, 25 (12.5 %);
      underestimation, 3 (1.5 %)] patients showed discrepant results for diagnosis of
      significant fibrosis and cirrhosis, respectively. HAI and interquartile range
      (IQR) were the factors predictive of overestimation in cirrhosis. CONCLUSIONS:
      Fibrosis and necroinflammatory activity are the main determinants of TE in CHBV
      infection. Overestimation of actual fibrosis stage by TE is common and is
      influenced by necroinflammatory activity and IQR for estimation of cirrhosis.

PMID- 26201628
TI  - Response to peginterferon-alpha 2b and ribavirin in Japanese patients with
      chronic hepatitis C genotype 1.
AB  - PURPOSE: Patient age and gender may be associated with response to peginterferon
      alpha plus ribavirin, the current standard of care (SOC) for chronic hepatitis C
      genotype 1. We queried whether there was an association between age, gender, and
      treatment response to SOC in Japanese patients infected with hepatitis C virus
      (HCV) genotype 1. METHODS: Between 2006 and 2009, HCV-infected Japanese patients
      treated with peginterferon alpha-2b plus ribavirin for 48 weeks were enrolled.
      Patients were allocated into four groups according to age and gender, and
      epidemiological data and treatment outcomes were retrospectively analyzed. HCV
      RNA was measured with COBAS AMPLICOR HCV Monitor Test v. 2.0. RESULTS: The
      overall sustained virological response (SVR) rate was 49.8%: patients aged <=65
      and >65 years, 50.9 and 44.0%, respectively; male and female, 56.5 and 39.0%. SVR
      rates of SOC against HCV genotype-1 females aged >65 years (19.0%) were inferior
      to those in males aged >65 years (57.8%) in Japan. Multivariate logistic
      regression analysis showed that SVR was attained independently of adherence
      80/80/80 in all groups. CONCLUSIONS: Adherence to medication is also a key factor
      for the eradication of HCV in patients aged >65 years. As the SVR rate of
      patients aged <=65 years was similar to that of patients aged >65 years, SOC
      could be useful for treating some of the elderly patients.

PMID- 26201629
TI  - Association of ITPA gene variation and serum ribavirin concentration with a
      decline in blood cell concentrations during pegylated interferon-alpha plus
      ribavirin therapy for chronic hepatitis C.
AB  - BACKGROUND: Genetic variation leading to inosine triphosphatase (ITPA) deficiency
      protects chronic hepatitis C patients receiving ribavirin against hemolytic
      anemia. The relationship between ITPA gene variation and serum ribavirin
      concentration was analyzed in association with a reduction in blood cells and
      dose reduction of pegylated interferon (PEG-IFN) or ribavirin. PATIENTS AND
      METHODS: A total of 300 hepatitis C patients treated with PEG-IFN plus ribavirin
      were analyzed. Genetic polymorphisms were determined in ITPA and the quantitative
      reduction in blood cells from the baseline was analyzed every 4 weeks for the
      duration of treatment and after the end of therapy. The decline in hemoglobin
      (Hb) or platelet (PLT) level at week 4 compared to baseline was also assessed
      according to ribavirin concentrations. RESULTS: Patients with the ITPA-CA/AA
      genotypes showed a lower degree of Hb reduction throughout therapy than those
      with the ITPA-CC genotype and a marked difference in mean Hb reduction was found
      at week 4 (CA/AA -1.0 vs. CC -2.8, p < 0.001). The ITPA-CC genotype had
      significantly less reduction in the mean platelet count than the ITPA-CA/AA
      genotypes early during treatment (p < 0.001 for weeks 4 and 8). Patients with the
      ITPA-CA/AA genotypes were less likely to develop anemia, regardless of the
      concentration of ribavirin. Patients with baseline PLT counts below 130 *
      10(3)/MUl had a significantly lower tendency to achieve sustained virological
      response (SVR), especially those with the ITPA-CA/AA genotypes. ITPA gene
      variation was not extracted by multivariable analysis as an important predictor
      of SVR. CONCLUSIONS: Despite the fact that ITPA variants were less likely to
      develop anemia, patients with low baseline PLT counts were difficult to treat,
      especially those with the ITPA-CA/AA genotype. These results may give a valuable
      pharmacogenetic diagnostic tool for the tailoring of dosing to minimize drug
      induced adverse events.

PMID- 26201631
TI  - Association of IL28B genotypes with metabolic profiles and viral clearance rate
      in chronic hepatitis C patients.
AB  - PURPOSE: IL28B genotypes have a strong impact on treatment outcomes of chronic
      hepatitis C (CHC) and on-treatment viral kinetics. Since metabolic regulation and
      interferon response are highly integrated, metabolic profiles may play an
      important role in the link between IL28B genotypes and hepatitis C virus (HCV)
      infection. Thus, the association of IL28B rs8099917 genotypes with metabolic
      profiles and the impact of metabolic profiles on hepatitis C viral kinetic
      parameters were examined. METHODS: A case-control analysis including 278 CHC
      patients and 280 subjects without chronic HCV infection was performed. The
      associations of IL28B rs8099917 genotype with pretreatment metabolic profiles and
      early viral kinetic parameters were evaluated. RESULTS: Compared to HCV genotype
      1 patients, the differences in metabolic profiles were more significant in
      genotype 2 patients. HCV genotype 2 patients with TT genotype had higher serum
      total cholesterol and high density lipoprotein (HDL) levels than those with GT
      genotype, and the differences remained significant when adjusted for age, sex,
      and body mass index (p = 0.005 for total cholesterol; p = 0.006 for HDL). In
      addition, patients with higher serum TG, higher fasting blood glucose, and lower
      HDL had a lower viral clearance rate. CONCLUSIONS: IL28B genotypes may affect
      lipid profiles of CHC patients, especially in HCV-genotype 2 patients. Patients
      with higher serum fasting blood glucose, triglyceride, and lower HDL have a lower
      viral clearance rate during pegylated interferon plus ribavirin therapy.

PMID- 26201630
TI  - Interferon-associated hepatic steatosis is related to discrepancies in
      biochemical and virological responses of chronic hepatitis C to IFN-based
      therapy.
AB  - BACKGROUND AND AIMS: A discrepancy in virological and biochemical responses may
      occur throughout interferon-based therapy for hepatitis C virus (HCV). We aimed
      to explore the risk, associated factors, potential mechanisms, and impact on the
      treatment outcome of the discrepancy. SUBJECTS AND METHODS: Consecutive 496,
      chronic HCV-infected patients receiving interferon/ribavirin or
      peginterferon/ribavirin for 24 weeks with a 24-week follow-up period were
      enrolled. Of 433 patients with pretreatment liver biopsy, 46 received serial
      liver biopsies at the end of treatment and end of follow-up to explore the
      corresponding change in liver histopathology. A virological/biochemical
      discrepancy was defined as persistently elevated alanine aminotransferase levels
      throughout the treatment period, despite the seronegativity for HCV RNA at least
      at the end of treatment. The sustained virological response (SVR) was defined as
      seronegativity for HCV RNA 6 months after the end of treatment. RESULTS:
      Virological/biochemical discrepancy was observed in 28.7 % (137/478) patients.
      The SVR rate was comparable between patients with (75.2 %, 103/137) and without
      discrepancy (81.2 %, 277/341, p = 0.14). For patients with discrepancy and SVR,
      78 (75.7 %) had a subsequent normalization of alanine aminotransferase. Hepatic
      steatosis, advanced fibrosis, obesity, older age, peginterferon preparation, and
      low viral load were independently predictive of a virological/biochemical
      discrepancy. Serial liver histology showed that significant transient aggravation
      of hepatic steatosis during interferon-based therapy was observed among patients
      with a virological/biochemical discrepancy (difference 0.64 +/- 0.93, p = 0.022),
      but not among those without it (difference 0.09 +/- 0.69, p = 0.447).
      CONCLUSIONS: A virological/biochemical discrepancy no longer exists after
      treatment cessation in most patients, and had little impact on the HCV treatment
      outcome. Treatment-related hepatic steatosis might play an important role in the
      pathogenesis of the discrepancy.

PMID- 26201632
TI  - The safety and efficacy of peginterferon plus ribavirin in hepatitis C patients
      concomitant with malignancy other than hepatocellular carcinoma: a multicenter
      study.
AB  - PURPOSE: Cancer patients were generally excluded from the therapeutic guidelines
      of antiviral therapy. We aimed to evaluate the efficacy and safety of antiviral
      therapy in patients with hepatitis C virus (HCV) infection concomitant with
      malignancy other than hepatocellular carcinoma (HCC). METHODS: Twenty-five HCV
      patients with curative malignancy other than HCC (group A) and 75 sex- and age
      matched controls (group B) were recruited into a prospective and case-control
      analysis. All patients received peginterferon-alpha-2a (PegIFN-alpha-2a) and
      weight-based ribavirin according to the current treatment recommendations. The
      primary outcome measurement was sustained virological response (SVR). The safety
      issue between groups was also compared. RESULTS: There were 22 (88.0 %) patients
      of group A and 59 (78.7 %) patients of group B who achieved an SVR (p = 0.39).
      The SVR rate was comparable between groups both in genotype-1 (HCV-1) (81.8 vs.
      72.7 %, p = 0.70) and in genotype-2 (HCV-2) (92.9 vs. 83.3 %, p = 0.66) patients.
      Multivariate logistic regression analysis demonstrated that the achievement of a
      RVR (viral clearance during first 4 weeks of treatment) was the strongest
      predictor of an SVR (odds ratio/95 % confidence intervals [OR/CI]: 6.357/1.50 -
      26.99, p = 0.01), followed by lower baseline viral loads (OR/CI: 0.403/0.174 -
      0.936, p = 0.034) and higher dose of ribavirin exposure (OR/CI: 1.287/1.092 -
      1.517, p = 0.003), whilst previous occurrence of cancer was not associated with
      SVR. Treatment adherence (76.0 vs. 72.0 %, p = 0.70) and the incidences of grade
      3 or more adverse events (28.0 vs. 20.0 %, p = 0.40) were comparable between two
      groups. CONCLUSIONS: Chronic hepatitis C patients with non-HCC malignancies
      receiving peginterferon/ribavirin combination therapy carried favorable efficacy
      and safety outcomes.

PMID- 26201633
TI  - Ascites in patients with hepatocellular carcinoma: prevalence, associated
      factors, prognostic impact, and staging strategy.
AB  - PURPOSE: Ascites may develop in patients with hepatocellular carcinoma (HCC) with
      coexisting liver cirrhosis. Few studies had specifically evaluated the role of
      ascites in HCC. This study investigated its prevalence, associated factors,
      prognostic impact, and staging strategy in a large HCC patient cohort. PATIENTS
      AND METHODS: A total of 2,203 HCC patients were analyzed. The grading of ascites
      was according to the European Association for the Study of Liver. The prognostic
      ability of the Cancer of the liver Italian Program (CLIP), Barcelona Clinic Liver
      Cancer, Japan Integrated Scoring system, and Taipei Integrated Scoring system in
      HCC patients with ascites was compared using the Akaike information criterion
      (AIC). RESULTS: Ascites was present in 498 (23%) patients at diagnosis. Grades 1,
      2, and 3 ascites were found in 13, 5, and 5% of the patients, respectively. The
      severity of ascites significantly correlated with hyperbilirubinemia,
      hypoalbuminemia, hyponatremia, prothrombin time (PT) prolongation, and renal
      insufficiency (all p < 0.001). Large tumor burden and more frequent vascular
      invasion were often observed in patients with more severe ascites (both p <
      0.001). In the Cox proportional hazard model, ascites was identified as an
      independent prognostic predictor with 80-94% increased risk of mortality (p <
      0.001). Among HCC patients with ascites, the CLIP system had the lowest AIC
      value. CONCLUSIONS: Ascites is often seen in HCC patients and is associated with
      both tumoral and cirrhosis factors and decreased long-term survival. The CLIP
      staging system is a more feasible prognostic model for HCC patients with ascites.
      The optimal treatment strategy for these patients remains to be investigated.

PMID- 26201634
TI  - Serum miR-483-5p as a potential biomarker to detect hepatocellular carcinoma.
AB  - BACKGROUND AND GOALS: There are no highly sensitive and specific minimally
      invasive biomarkers for hepatocellular carcinoma (HCC) to date. The objective of
      this study was to identify serum microRNAs (miRNAs) as potential HCC biomarkers.
      METHODS: Using miRCURY LNATM microRNA arrays, the levels of circulating miRNAs in
      the serum of patients with HCC were compared and controls were matched. Then 253
      subjects (112 HCC, 85 chronic hepatitis B [CHB], and 56 healthy controls) were
      recruited and 12 serum miRNAs were compared by quantitative real-time polymerase
      chain reaction (qRT-PCR). It was followed by the comparison of serum miRNA
      concentrations before and after the surgical resection in HCC group. RESULTS:
      Median levels of miR-483-5p and miR-500a were higher in HCC patients than in
      patients with CHB and in healthy controls (p < 0.0001), but there were no
      differences between CHB patients and healthy controls (p > 0.05) and miR-483-5p
      levels were significantly reduced in serum samples obtained 30 days after
      surgical resection (p < 0.0001). The area under receiver operating characteristic
      curves of miR-483-5p and miR-500a was 74% (cutoff [Ct] value = 2.824, sensitivity
      = 74%, and specificity = 66%) and 66% (Ct value = 1.830, sensitivity = 74%, and
      specificity = 51%) for the prediction of HCC, respectively. In detecting HCC,
      combining alpha-fetoprotein (AFP) and serum miR-483-5p (sensitivity = 81% and
      specificity = 83%) was better than AFP alone (sensitivity = 78%, specificity =
      70%). CONCLUSION: Our observations suggest that serum miR-483-5p and miR-500a
      might serve as novel, noninvasive biomarkers for HCC. Serum miR-483-5p might
      complement AFP in detecting HCC.

PMID- 26201635
TI  - Copy-number variations in hepatoblastoma associate with unique clinical features.
AB  - PURPOSE: Hepatoblastoma is a rare childhood liver malignancy with limited
      relevant cytogenetic data. This study aimed to discover common genomic copy
      number variations (CNVs) in subjects with hepatobalstoma and its relevance to the
      clinical course. METHODS: Gene copy-number was systemically rated by high
      resolution comparative genomic hybridization (CGH) DNA oligonucleotide
      microarray. The study group consisted of 12 children (7 males and 5 females) with
      hepatoblastoma and another 20 healthy individuals (10 males and 10 females) as
      controls. The influence of recurrent CNVs on clinical outcomes was analyzed.
      RESULTS: Four highly recurrent CNVs were identified in these 12 hepatoblastoma
      children after comparison with controls, including a gain on 1p13.3 (n = 3, 25%)
      and losses on 5p15.33 (n = 4, 33.3%), 16q12.2 (n = 4, 33.3%), and 19q13.42 (n =
      3, 25%). The most prevalent sites of genomic deletion were 5p15.33 and 16q12.2.
      Zinc finger, DHHC-type containing 11 (ZDHHC11) and DHHC-type containing 11B
      (ZDHHC11B) were mapped to 5p15.33, which was associated with a lower rate of
      survival with native liver (p = 0.03). The carboxylesterase 4-like (CES4) gene
      that mapped to 16q12.2 was associated with smaller tumor size at presentation.
      CONCLUSIONS: Deletions of 5p15.33 (33.3%) and 16q12.2 (33.3%) are the most
      frequent hepatoblastoma-related events in our patient group with 5p15.33
      microdeletion as a potential biomarker for the fate of survival with native
      liver.

PMID- 26201636
TI  - Up-regulation of dbpA mRNA in hepatocellular carcinoma associated with metabolic
      syndrome.
AB  - PURPOSE: Metabolic syndrome (MS) is a group of recognized risk factors for the
      development of hepatocellular carcinoma (HCC) in patients with chronic liver
      disease. The aim of this study was to analyze the clinicopathological
      characteristics of HCC patients with MS and the risk factors for recurrence.
      Also, the aim was to investigate the cold shock protein: DNA-binding protein A
      (dbpA) expression in HCC patients with MS. METHODS: A total of 243 patients who
      underwent curative resections for HCC were classified into two groups. dbpA
      expression was investigated in 66 HCC patients with MS and in 30 patients without
      MS by using real-time RT-PCR. Promoter methylation status was examined by using
      MS-PCR. RESULTS: The incidence of metabolic factors affect the HCC significantly
      higher in non-B non-C patients than in hepatitis B virus (HBV) or hepatitis C
      virus (HCV) patients (P < 0.001). Univariate analysis of HCC patients with MS
      recurrence revealed aspartate amino transferase (AST), multiple tumors, liver
      damage, hepatic vein invasion, advanced cancer stages (P < 0.01), alpha
      fetoprotein (AFP) and diabetes mellitus type II (P < 0.05) as risk factors.
      Multivariate analysis, AST, multiple tumors, and hepatic vein invasion (P < 0.01)
      were identified as independent factors for the recurrence. dbpA mRNA was higher
      in patients with MS than in those without MS (P = 0.016), and it was mostly
      upregulated in non-B non-C HCC patients with MS than in non-B non-C HCC patients
      without HBV or HCV. Especially, in HCC patients with diabetes mellitus type II,
      the mRNA and protein levels were highly upregulated. The dbpA expression was
      regulated by promoter methylation status (P < 0.05). CONCLUSIONS: This study
      identifies that dbpA may accelerate the hepatocarcinogenesis in HCC patients with
      MS via inflammation-induced and oxidative stress pathways. The demethylation
      related epigenetic activation may be one of the regulating factors for HCC
      patients with MS.

PMID- 26201637
TI  - A nationwide population-based study shows increasing incidence of
      cholangiocarcinoma.
AB  - PURPOSE: An increasing incidence of cholangiocarcinoma (CCA) has been reported in
      Western countries, but evidence is lacking in Asia. We investigated the incidence
      of CCA in a nationwide cohort. PATIENTS AND METHODS: We conducted a nationwide
      cohort study based on data from the Taiwan National Health Insurance Research
      Database (NHIRD) between 1998 and 2008. A total of 6,491 CCA patients were
      recruited. Adjusted incidences, cumulative incidences, and stratified analyses
      were used to detect trends regarding CCA incidence in Taiwan. RESULTS: The
      incidence of CCA increased by 2.01-fold, from 1.79 in 1998 to 3.60 in 2008 per
      100,000 persons. For extrahepatic CCA, the incidence increased by 1.5-fold from
      0.48 to 0.73 per 100,000. Intrahepatic CCA increased by 3.0-fold from 0.72 to
      2.19 per 100,000. The rising incidence of CCA was observed across all sexes and
      ages, especially in those older than 65 years of age. The proportion of CCA
      patients who underwent surgery and the overall survival rates remained stable.
      CONCLUSIONS: The incidence of both intrahepatic and extrahepatic CCA increased
      significantly between 1998 and 2008. Rising trends were observed among different
      ages and sexes, especially in the elderly population.

PMID- 26201638
TI  - Short- and long-term clinical outcome after balloon-occluded retrograde
      transvenous obliteration: is pretreatment portal flow direction a predictive
      factor?
AB  - PURPOSE: To determine whether pretreatment portal flow direction can predict
      different clinical manifestations or prognosis after balloon-occluded retrograde
      transvenous obliteration (B-RTO) for gastric varices. METHODS: The subjects were
      103 cirrhotic patients with medium- or large-grade gastric varices treated by B
      RTO. Short- and long-term clinical outcomes were compared among patients with
      forward portal flow (F group) and those with reversed or to-and-fro portal flow
      (R group) on color Doppler sonography before B-RTO. RESULTS: Deterioration of
      liver function reserve 1 year after B-RTO was more frequent in the R group (34.7
      %) than in the F group (11.1 %, p = 0.0251). Thrombotic disorders within 1 year
      after B-RTO were also more frequent in the R group (20.7 %) than in the F group
      (2.7 %, p = 0.0079). There was no significant difference in cumulative survival
      rate of Child class A patients between the two groups. In Child class B or class
      C patients, however, the cumulative survival rate was poorer in the R group
      (68.7, 30.5, and 30.5 % at 1, 5, and 9 years, respectively) than in the F group
      (94.9, 58.8, and 37.8 % and 1, 5, and 9 years, respectively; p = 0.0097).
      CONCLUSIONS: Hemodynamic assessment of portal flow direction is important before
      B-RTO, and care should be taken to manage thrombotic disorders in the
      perioperative period in patients with reversed portal flow after B-RTO. Another
      treatment option might be preferred for gastric varices in Child classes B and C
      patients with reversed portal flow instead of B-RTO, which may have a poor
      prognosis.

PMID- 26201639
TI  - Early primary prophylaxis with beta-blockers does not prevent the growth of small
      esophageal varices in cirrhosis: a randomized controlled trial.
AB  - BACKGROUND: The efficacy of portal pressure reduction by beta-blockers and the
      utility of serial hepatic venous pressure gradient (HVPG) measurements for the
      management of small (<=5 mm) esophageal varices in patients of cirrhosis are not
      clear. AIMS: The study had the following aims: to study (1) the effect of
      propranolol on the growth of small varices and (2) whether single or serial HVPG
      measurements result in a better outcome compared to no measurement in patients
      with small varices. METHODS: Consecutive cirrhosis patients with small varices,
      without any history of variceal bleed, were randomized to receive propranolol or
      placebo and to undergo no HVPG, only baseline HVPG, or serial HVPG measurements.
      RESULTS: A total of 150 cirrhotics (cirrhosis predominantly viral or alcohol
      induced) were included (77 in the beta-blocker and 73 in the placebo group).
      Baseline characteristics were similar. The actuarial 2-year risk of growth of
      varices (primary endpoint) was 11 and 16% in the propranolol and placebo group,
      respectively (P = 0.786). Variceal bleeding and mortality were also comparable in
      the two groups. Similarly, the outcome was not influenced by HVPG measurements
      (whether serial, only baseline, or no HVPG). A bilirubin level of >=1.5 mg/dl was
      found to be an independent predictor of variceal progression. CONCLUSIONS: In
      cirrhotics with small esophageal varices, nonselective beta-blockers are unable
      to prevent the growth of varices, variceal bleed, or mortality. HVPG monitoring
      of these patients did not change the outcome; however, the role of HVPG-guided
      therapy modification needs to be studied.

PMID- 26201640
TI  - The effect of systemic antibiotic prophylaxis for cirrhotic patients with peptic
      ulcer bleeding after endoscopic interventions.
AB  - PURPOSE: All previous studies reported the benefit of antibiotic prophylaxis in
      cirrhotic patients with either a mixture of nonvariceal and variceal bleeding or
      variceal bleeding alone. Reports on sole peptic ulcers bleeding are lacking. We
      aimed to assess the effect of antibiotic prophylaxis in cirrhotic patients with
      peptic ulcer bleeding after endoscopic interventions and the risk factors
      associated with recurrent bleeding. METHODS: A cross-sectional retrospective
      chart review study was conducted on 148 cirrhotic patients with acute peptic
      ulcer hemorrhage who underwent therapeutic endoscopic procedures. Patients who
      received prophylactic intravenous ceftriaxone were classified as group A (n = 38)
      and those who did not receive antibiotics were classified as group B (n = 110).
      The outcomes were prevention of infection, length of hospital stay, time of
      rebleeding, and death. RESULTS: More patients suffered from recurrent bleeding
      and infection in group B than those in group A (28.2 vs. 5.3 %; p = 0.003, and
      26.4 vs. 10.5 %; p = 0.043, respectively). The risk factors associated with
      recurrent bleeding were being male (OR = 3.4; p = 0.024), those with advanced
      stage of cirrhosis with Child-Pugh's class C (OR = 3.8; p < 0.001), and those
      without antibiotic prophylaxis (OR = 8.9; p = 0.003). The observed 30-day
      survival was virtually identical for both groups (p = 0.279). CONCLUSIONS:
      Antibiotic prophylaxis in cirrhotic patients after endoscopic interventions for
      acute peptic ulcer hemorrhage reduced infections and decreased rebleeding. Male
      gender, cirrhosis Child-Pugh's class C, and no antibiotic prophylaxis were
      independent predictors of recurrent bleeding. Further studies should be directed
      to explore ways to improve the overall outcome of these patients.

PMID- 26201641
TI  - Small intestinal bacterial overgrowth and delayed orocecal transit time in
      patients with cirrhosis and low-grade hepatic encephalopathy.
AB  - BACKGROUND: Hepatic encephalopathy (HE) is associated with poor prognosis in
      cirrhosis. Gut-derived nitrogenous substances play a role in pathogenesis of HE.
      The present study was conducted to assess small intestinal bacterial overgrowth
      (SIBO) and prolonged orocecal transit time (OCTT) in cirrhosis and low-grade HE.
      METHODS: In cross-sectional prospective study, 75 patients were divided into 3
      groups: group 1 (no HE, n = 31), group 2 (minimal HE, n = 29), and group 3
      (early/grade 1 HE, n = 15). Minimal HE (MHE) was diagnosed when psychometric
      hepatic encephalopathy score (PHES) was <=5. Early HE was diagnosed, according to
      West Haven criteria. All patients underwent glucose hydrogen breath test (GHBT)
      for SIBO and lactulose hydrogen breath test (LHBT) for OCTT. RESULTS: A total of
      29 patients (38.67 %) had MHE and 15 (20 %) had early HE. Prevalence of MHE in
      Child-Turcotte-Pugh (CTP) class A, B, and C was 33.3, 38.71, and 45 %,
      respectively, while SIBO was detected in 26 (34.67 %). Prevalence of SIBO was
      12.5 % in CTP class A, 41.94 % in CTP class B, and 50 % in CTP class C. Five
      (16.13 %) patients in no HE group had SIBO as compared to 14 (48.28 %) in MHE
      group and 7 (46.67 %) in early HE group (p = 0.018). OCTT was 111.13 +/- 13.95
      min in patients with no HE as compared to 137.59 +/- 14.80 min in patients with
      MHE and 150 +/- 15.12 min in patients with early HE (p < 0.001). OCTT was
      significantly prolonged in patients with SIBO (145 +/- 17.49 min) than in those
      without SIBO (120.71 +/- 18.3 min) (p < 0.001). CONCLUSION: SIBO and delayed OCTT
      are more common with MHE and early HE in patients with cirrhosis.

PMID- 26201642
TI  - Spontaneous bacterial empyema in patients with liver cirrhosis in Upper Egypt:
      prevalence and causative organisms.
AB  - BACKGROUND: Spontaneous bacterial empyema (SBEM) is a complication in cirrhotic
      patients, in which a preexisting pleural effusion becomes infected. PURPOSE: The
      purpose was to determine the prevalence and causative organisms of SBEM among
      cirrhotic patients with hydrothorax. MATERIALS AND METHODS: This descriptive,
      cross-sectional study included 901 cirrhotic patients. All patients underwent
      clinical evaluation, liver function tests, chest X-ray, abdominal and chest
      ultrasonography, and pleural and peritoneal fluids study (when detected)
      including polymorphonuclear (PMN) leukocyte count, biochemical analysis, and
      culture by two methods: conventional and modified (inoculation of 10 mL of
      pleural or peritoneal fluid into a blood culture bottle). Diagnostic criteria for
      SBEM included positive pleural fluid culture and a PMN count of >250 cells/mm(3)
      or, if a negative culture, a pleural fluid PMN count of >500 cells/mm(3) and the
      absence of pneumonia on chest radiography. RESULTS: Of 901 cirrhotic patients, 16
      cases of SBEM were diagnosed. The prevalence of SBEM was 1.8 % in cirrhotic
      patients and 26.2 % in patients with cirrhosis and hydrothorax. Pleural fluid
      culture was found to be positive by the conventional method in four (25 %) cases
      and by modified methods in 11 (68.8 %) cases. Escherichia coli was the most
      frequently isolated pathogen (six cases). The mortality rate of SBEM was 25 %.
      CONCLUSIONS: SBEM is a frequent complication in cirrhotic patients with
      hydrothorax. E. coli is the most frequent organism responsible for SBEM. The
      modified method of pleural fluid culture is more sensitive than the conventional
      method for diagnosis of SBEM.

PMID- 26201643
TI  - Obesity, type 2 diabetes, age, and female gender: significant risk factors in the
      development of alcoholic liver cirrhosis.
AB  - BACKGROUND: Recent epidemiological studies show that alcoholic liver cirrhosis
      (ALC) continues to increase in spite of a gradual decrease in the alcohol intake
      beyond 1999, indicating that there are other risk factors for the development of
      ALC. METHODS: A nationwide survey of liver cirrhosis (LC) was undertaken by
      asking major hospital institutions to provide the number of patients with LC
      admitted between 2007 and 2008 together with their etiologic findings including
      the daily intake of alcohol, period of drinking, and other relevant demographic
      measurements. RESULTS: The intake of alcohol in female ALC patients was lower
      together with a shorter drinking period versus male patients. The prevalence of
      diabetes mellitus (DM) in ALC patients was higher in habitual drinkers (<110
      g/day) than in heavy drinkers (>=110 g/day), 49.5 versus 20.3%, respectively (P <
      0.001). In male ALC patients, the prevalence of DM was higher in habitual
      drinkers, 55.2 versus 20.6% for the female gender (P < 0.001). The same tendency
      was seen in patients with a body mass index >=25. The prevalence of obesity was
      higher in habitual drinkers than in heavy drinkers, 49.7 versus 31.1%,
      respectively. More than 90% of the male habitual drinkers either had DM or were
      obese, whereas less than half of the female habitual drinkers had a concomitant
      complication. More than 70% of the male ALC patients were over 60 years.
      CONCLUSION: Obesity, DM, age, and female gender appear to be additional
      significant risk factors for ALC. Our impression is that these additional risk
      factors might help to identify alcoholic patients who may progress to ALC even
      without excessive alcohol intake.

PMID- 26201644
TI  - Comparative proteomic analysis of human donor tissues during orthotopic liver
      transplantation: ischemia versus reperfusion.
AB  - PURPOSE: To explore the specific alterations in protein profiles that occur
      during ischemia/reperfusion injury (I/RI) and find novel therapeutic strategies
      to reduce I/RI during orthotopic liver transplantation (OLT). METHOD: We used the
      comparative proteomic approach of two-dimensional electrophoresis (2-DE) and
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) to compare the proteomic profiles of the same donor liver at three
      different time points: T1, immediately after cardiac arrest of donors (normal
      control); T2, before portal vein anastomosis (ischemia); and T3, 2 h after
      hepatic artery anastomosis (reperfusion). RESULT: We identified 34 proteins that
      were significantly altered during I/RI. These differentially expressed proteins
      were functionally classified into seven categories: metabolic enzyme, molecular
      chaperone, antioxidant enzyme, cytoskeleton protein, signal transduction protein,
      cyclin, and binding protein. Among the 34 proteins, 9 changed during ischemia
      only (from T1 to T2), 11 changed during reperfusion only (from T2 to T3), and the
      others changed during both ischemia and reperfusion (from T1 to T3) periods.
      CONCLUSION: Ischemia and reperfusion during LT may lead to different
      modifications of the liver proteins. Most metabolic enzymes and antioxidant
      enzymes were upregulated during ischemia, indicating that lipid metabolic
      disorder and oxidative stress are closely related to the development of ischemic
      injury. ER chaperones may play a vital role in mediating I/RI and preventing ER
      stress caused by I/RI. Modulation of ER chaperones could be used as a key
      therapeutic target to improve the outcomes of LT.

PMID- 26201645
TI  - Effect of piperine on the bioavailability and pharmacokinetics of emodin in rats.
AB  - Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has been widely used as a
      traditional medicine and was shown to possess a multitude of health-promoting
      properties in pre-clinical studies, but its bioavailability was low due to the
      extensive glucuronidation in liver and intestine, hindering the development of
      emodin as a feasible chemopreventive agent. In this study, piperine, as a
      bioenhancer, was used to enhance the bioavailability of emodin by inhibiting its
      glucuronidation. The pharmacokinetic profiles of emodin after oral administration
      of emodin (20mg/kg) alone and in combination with piperine (20mg/kg) to rats were
      investigated via a validated LC/MS/MS method. As the in vivo pharmacokinetic
      studies had indicated, the AUC and Cmax of emodin were increased significantly
      after piperine treatment, and the glucuronidation of emodin was markedly
      inhibited. Our study demonstrated that piperine significantly improved the in
      vivo bioavailability of emodin and the influence of piperine on the
      pharmacokinetics of emodin may be attributed to the inhibition of glucuronidation
      of emodin. Further research is needed to investigate the detailed mechanism of
      improved bioavailability of emodin via its combination with piperine.

PMID- 26201646
TI  - Of mice and men.

PMID- 26201647
TI  - [Breast cancer in men: about 3 cases at the l'Hopital d'instruction des armees
      Omar Bongo Ondimba (HIAOBO) (Gabon)].
AB  - We report three cases of breast cancer in men observed at Military Teaching
      Hospital Omar Bongo Ondimba between January 2008 and December 2009, under varying
      circumstances, with all unfavorable evolution.

PMID- 26201649
TI  - Terminal investment in the gustatory appeal of nuptial food gifts in crickets.
AB  - Investment in current versus future reproduction represents a prominent trade-off
      in life-history theory and is likely dependent on an individual's life
      expectancy. The terminal investment hypothesis posits that a reduction in
      residual reproductive value (i.e. potential for future offspring) will result in
      increased investment in current reproduction. We tested the hypothesis that male
      decorated crickets (Gryllodes sigillatus), when cued to their impending
      mortality, should increase their reproductive effort by altering the composition
      of their nuptial food gifts (i.e. spermatophylaxes) to increase their gustatory
      appeal to females. Using a repeated-measures design, we analysed the amino acid
      composition of spermatophylaxes derived from males both before and after
      injection of either a saline control or a solution of heat-killed bacteria. The
      latter, although nonpathogenic, represents an immune challenge that may signal an
      impending survival threat. One principal component explaining amino acid
      variation in spermatophylaxes, characterized by a high loading to histidine, was
      significantly lower in immune-challenged versus control males. The relevance of
      this difference for the gustatory appeal of gifts to females was assessed by
      mapping spermatophylax composition onto a fitness surface derived in an earlier
      study identifying the amino acid composition of spermatophylaxes preferred by
      females. We found that immune-challenged males maintained the level of
      attractiveness of their gifts post-treatment, whereas control males produced
      significantly less attractive gifts post-injection. These results are consistent
      with the hypothesis that cues of a survival-threatening infection stimulate
      terminal investment in male decorated crickets with respect to the gustatory
      appeal of their nuptial food gifts. 

PMID- 26201648
TI  - Identification and Characterization of a Novel Family of Cysteine-Rich Peptides
      (MgCRP-I) from Mytilus galloprovincialis.
AB  - We report the identification of a novel gene family (named MgCRP-I) encoding
      short secreted cysteine-rich peptides in the Mediterranean mussel Mytilus
      galloprovincialis. These peptides display a highly conserved pre-pro region and a
      hypervariable mature peptide comprising six invariant cysteine residues arranged
      in three intramolecular disulfide bridges. Although their cysteine pattern is
      similar to cysteines-rich neurotoxic peptides of distantly related protostomes
      such as cone snails and arachnids, the different organization of the disulfide
      bridges observed in synthetic peptides and phylogenetic analyses revealed MgCRP-I
      as a novel protein family. Genome- and transcriptome-wide searches for
      orthologous sequences in other bivalve species indicated the unique presence of
      this gene family in Mytilus spp. Like many antimicrobial peptides and
      neurotoxins, MgCRP-I peptides are produced as pre-propeptides, usually have a net
      positive charge and likely derive from similar evolutionary mechanisms, that is,
      gene duplication and positive selection within the mature peptide region;
      however, synthetic MgCRP-I peptides did not display significant toxicity in
      cultured mammalian cells, insecticidal, antimicrobial, or antifungal activities.
      The functional role of MgCRP-I peptides in mussel physiology still remains
      puzzling. 

PMID- 26201650
TI  - The sexual networks of racially diverse young men who have sex with men.
AB  - Young men who have sex with men are at increased risk for HIV. Research with
      older men and high-risk populations suggests that network dynamics may contribute
      to the spread of infectious disease and HIV, but little is known about the sexual
      networks of young men who have sex with men. Utilizing a unique dataset, this
      study presents novel descriptive data about the sexual networks of racially
      diverse 17- to 23-year-old young men who have sex with men. Additionally,
      individual, partner, and network characteristics of these young men who have sex
      with men were examined as potential drivers of HIV, STI, and unprotected
      intercourse. Results indicated several partner- and network-level factors
      associated with HIV and associated outcomes. 

PMID- 26201651
TI  - Hydrolysis and volatile fatty acids accumulation of waste activated sludge
      enhanced by the combined use of nitrite and alkaline pH.
AB  - Volatile fatty acids (VFAs) production from anaerobic digestion of waste
      activated sludge (WAS) is often limited by the slow hydrolysis and/or poor
      substrate availability. Increased attention has been given to enhance the
      hydrolysis and acidification of WAS recently. This study presented an efficient
      and green strategy based on the combined use of nitrite pretreatment and alkaline
      pH to stimulate hydrolysis and VFA accumulation from WAS. Results showed that
      both proteins and polysaccharides increased in the presence of nitrite,
      indicating the enhancement of sludge solubilization and hydrolysis processes.
      Mechanism investigations showed that nitrite pretreatment could disintegrate the
      sludge particle and disperse extracellular polymeric substances (EPS). Then,
      anaerobic digestion tests demonstrated VFA production increased with nitrite
      treatment. The maximal VFA accumulation was achieved with 0.1 g N/L nitrite
      dosage and pH 10.0 at a sludge retention time (SRT) of 7 days, which was much
      higher VFA production in comparison with the blank, sole nitrite pretreatment, or
      sole pH 10. The potential analysis suggested that the combined nitrite
      pretreatment and alkaline pH is capable of enhancing WAS digestion with a great
      benefit for biological nutrient removal (BNR).

PMID- 26201653
TI  - Coastal hydrogeological system of Mar Piccolo (Taranto, Italy).
AB  - The Mar Piccolo basin is an internal sea basin located along the Ionian coast
      (Southern Italy), and it is surrounded primarily by fractured carbonate karstic
      environment. Because of the karstic features, the main continental water inflow
      is from groundwater discharge. The Mar Piccolo basin represents a peculiar and
      sensitive environment and a social emergency because of sea water and sediment
      pollution. This pollution appears to be caused by the overlapping effects of
      dangerous anthropogenic activities, including heavy industries and commercial and
      navy dockyards. The paper aims to define the contribution of subaerial and
      submarine coastal springs to the hydrological dynamic equilibrium of this
      internal sea basin. A general approach was defined, including a hydrogeological
      basin border assessment to detect inflowing springs, detailed geological and
      hydrogeological conceptualisation, in situ submarine and subaerial spring
      measurements, and flow numerical modelling. Multiple sources of data were
      obtained to define a relevant geodatabase, and it contained information on
      approximately 2000 wells, located in the study area (1600 km(2)). The
      conceptualisation of the hydrogeological basin, which is 978 km(2) wide, was
      supported by a 3D geological model that interpolated 716 stratigraphic logs. The
      variability in hydraulic conductivity was determined using hundreds of pumping
      tests. Five surveys were performed to acquire hydro-geochemical data and spring
      flow-yield measurements; the isotope groundwater age was assessed and used for
      model validation. The mean annual volume exchanged by the hydrogeological basin
      was assessed equal to 106.93 10(6) m(3). The numerical modelling permitted an
      assessment of the mean monthly yield of each spring outflow (surveyed or not),
      travel time, and main path flow. 

PMID- 26201654
TI  - Feasibility of using a translucid inorganic hydrogel to build a biosensor using
      immobilized algal cells.
AB  - Anthropic activities generate contaminants, as pesticides and other pollutants,
      in the aquatic environment which present a real threat to ecosystems and human
      health. Thus, monitoring tools become essential for water managers to detect
      these chemicals before the occurrence of adverse effects. In this aim, algal cell
      biosensors, based on photosystem II activity measurement, have been designed for
      several years in previous studies. In this work, we study a new immobilization
      technique of algal cells in the aim of improving the performance of these
      biosensors. Immobilization was here achieved by encapsulation in a hybrid
      alginate/silica translucid hydrogel. The feasibility of this process was here
      assessed, and the biosensor designed was tested on the detection of chemicals in
      urban rainwaters. 

PMID- 26201652
TI  - A perspective on the potential risks of emerging contaminants to human and
      environmental health.
AB  - Technological, agricultural, and medical advances have improved the lifestyle of
      humankind. However, these advances have caused new problems that affect the
      environment and future generations. Emerging contaminants display properties such
      as low degradation potential and environmental persistence. In addition, most
      contaminants are lipophilic, which culminates in high bioaccumulation. The
      disposal of pharmaceuticals and personal care products into the environment
      underlies microbial and bacterial resistance. Plasticizers change several
      characteristics of industrialized materials, such as flexibility, but they are
      potentially carcinogenic and disrupt the endocrine system. Pesticides prevent the
      propagation of numerous kinds of pests; nevertheless, they exert neurotoxic and
      mutagenic effects, and they impact the environment negatively. Addition of flame
      retardants to a number of materials prevents flame propagation; however, after
      their release into the environment, these chemicals may bioaccumulate in
      organisms and disrupt the endocrine system, too. Surfactants can change the
      surface and interfacial properties of liquids, but their presence in the
      environment can interfere with countless enzymes and can even impair the
      endocrine system of various organisms and induce the feminization of species.
      Hence, gaining knowledge about emerging contaminants is increasingly important to
      minimize future damage and enable proper monitoring of each class of compounds in
      the environment which will help to improve legislation on this matter. 

PMID- 26201655
TI  - Acute and sub-chronic toxicity of four cytostatic drugs in zebrafish.
AB  - The acute and sub-chronic effects of four cytostatic drugs-5-fluorouracil (5-FU),
      cisplatin (CisPt), etoposide (ET) and imatinib mesylate (IM)-on zebrafish (Danio
      rerio) were investigated. Acute tests were carried out in a static system in
      accordance with the OECD guideline 203 for adult fish and the draft guideline for
      fish embryos (FET test) in order to find the LC50 values of the four cytostatic
      drugs. Early-life stage toxicity test on zebrafish was conducted according the
      OECD guideline 210 using the cytostatic drugs 5-FU and IM in a semistatic system
      with the objective of investigating the sub-chronic effects of the cytostatic
      drugs on fish. In adult fish, the cytostatic drugs 5-FU and ET did not pass the
      limit test, thus, are considered non-toxic. In case of cisplatin, LC50 was
      calculated at 64.5 mg L(-1), whereas in case of IM, LC50 was at 70.8 mg L(-1). In
      the FET test, LC50 of 5-FU at 72-h post fertilization (hpf) was 2441.6 mg L(-1).
      In case of CisPt, LC50 was 349.9 mg L(-1) at 48 hpf and it progressively
      decreased to 81.3 mg L(-1) at 120 hpf. In addition, CisPt caused a significant
      delay in the hatch of larvae. In case of ET, LC50 values were not calculable as
      they were higher than 300 mg L(-1) at which concentration the substance
      crystallized in the solution. LC50 values of IM were 48 hpf; 158.3 mg L(-1) , 72
      hpf; 141.6 mg L(-1), 96 hpf; 118.0 mg L(-1), and 120 hpf; 65.9 mg L(-1). In the
      Early-life Stage Test with 5-FU, embryonic deformities were not detected during
      the tests. Regarding mortalities, the 10 mg L(-1) concentration can be considered
      as LOEC, as statistically significant difference in mortalities was detected in
      this group alone. Concerning dry body weight and standard length, 1 mg L(-1) is
      the LOEC. In case of IM, the highest tested concentration (10 mg L(-1)) can be
      considered LOEC for mortalities, however, the treatment did not have an effect on
      the other investigated parameters (dry and wet weight, standard length). All four
      cytostatic drugs were characterized by low toxicity in zebrafish in acute and sub
      chronic tests. 

PMID- 26201656
TI  - Distribution of P, K, Ca, Mg, Cd, Cu, Fe, Mn, Pb and Zn in wood and bark age
      classes of willows and poplars used for phytoextraction on soils contaminated by
      risk elements.
AB  - Fast-growing clones of Salix and Populus have been studied for remediation of
      soils contaminated by risk elements (RE) using short-rotation coppice
      plantations. Our aim was to assess biomass yield and distributions of elements in
      wood and bark of highly productive willow (S1--[Salix schwerinii * Salix
      viminalis] * S. viminalis, S2--Salix * smithiana clone S-218) and poplar (P1-
      Populus maximowiczii * Populus nigra, P2--P. nigra) clones with respect to aging.
      The field experiment was established in April 2008 on moderately Cd-, Pb- and Zn-
      contaminated soil. Shoots were harvested after four seasons (February 2012) and
      separated into annual classes of wood and bark. All tested clones grew on
      contaminated soils, with highest biomass production and lowest mortality
      exhibited by P1 and S2. Concentrations of elements, with exception of Ca and Pb,
      decreased with age and were higher in bark than in wood. The Salix clones were
      characterised by higher removal of Cd, Mn and Zn compared to the Populus clones.
      Despite generally higher RE content in young shoots, partly due to lower
      wood/bark ratios and higher RE concentrations in bark, the overall removal of RE
      was higher in older wood classes due to higher biomass yield. Thus, longer
      rotations seem to be more effective when phytoextraction strategy is considered.
      Of the four selected clones, S1 exhibited the best removal of Cd and Zn and is a
      good candidate for phytoextraction.

PMID- 26201657
TI  - Succulent species differ substantially in their tolerance and phytoextraction
      potential when grown in the presence of Cd, Cr, Cu, Mn, Ni, Pb, and Zn.
AB  - Plants for the phytoextraction of heavy metals should have the ability to
      accumulate high concentrations of such metals and exhibit multiple tolerance
      traits to cope with adverse conditions such as coexistence of multiple heavy
      metals, high salinity, and drought which are the characteristics of many
      contaminated soils. This study compared 14 succulent species for their
      phytoextraction potential of Cd, Cr, Cu, Mn, Ni, Pb, and Zn. There were species
      variations in metal tolerance and accumulation. Among the 14 succulent species,
      an Australian native halophyte Carpobrotus rossii exhibited the highest relative
      growth rate (20.6-26.6 mg plant(-1) day(-1)) and highest tolerance index (78
      93%), whilst Sedum "Autumn Joy" had the lowest relative growth rate (8.3-13.6 mg
      plant(-1) day(-1)), and Crassula multicava showed the lowest tolerance indices
      (<50%). Carpobrotus rossii and Crassula helmsii showed higher potential for
      phytoextraction of these heavy metals than other species. These findings suggest
      that Carpobrotus rossii is a promising candidate for phytoextraction of multiple
      heavy metals, and the aquatic or semiterrestrial Crassula helmsii is suitable for
      phytoextraction of Cd and Zn from polluted waters or wetlands.

PMID- 26201659
TI  - Phytotoxicity evaluation of some commonly used shampoos using Brassica napus L.
AB  - Hair shampoos are among the most commonly used chemicals in everyday life. Since
      shampoos are a major component of domestic and municipal wastewater, they may
      affect plants when irrigated with wastewater. However, their effects on plants
      have never been investigated in detail. The present study was aimed to evaluate
      the effect of some commonly used hair shampoos on seed germination and seedling
      vigor of Brassica napus. Seeds of Brassica napus were exposed to different
      concentrations of hair shampoos, i.e., 0 (control), 0.001, 0.01, 0.1, 1.0, and 10
      %. The obtained results revealed that germination was not very sensitive to
      shampoo stress and was significantly inhibited only at the highest tested
      concentration (10 %) of shampoo except in the case of one shampoo where it was
      inhibited at concentration of 1 % or above. The other tested parameters of
      Brassica napus were comparatively more sensitive than germination to shampoo
      stress. However, at lower concentrations of shampoos, stimulatory effects were
      also observed in some cases. Although no exact data is available on shampoo
      concentration in wastewater used for irrigation, it is unlikely that shampoo
      concentration in irrigation water reach so high and pose adversity to plants.

PMID- 26201658
TI  - Massive PCDD/F contamination at the Khimprom organochlorine plant in Ufa--a
      review and recommendations for future management.
AB  - The Khimprom plant in Ufa was one of the largest organochlorine production
      facilities in Russia. This paper summarises the residual pollution of the site
      with polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and highlights
      the current and future challenges in relation to remediation of the site.
      Preliminary assessment of the pollution shows large-scale PCDD/F contamination at
      the site from half a century production of organochlorine pesticides and
      solvents. This contamination is affecting the city, and 2500 residents live
      within 3 km with a further 350,000 living within 7 km of the factory. The current
      PCDD/F pollution of the site and the continuing releases highlight the urgent
      need for further investigations, for the site to be secured and for the
      contamination to be remediated. The production history of the plant means that
      also other unintentionally POPs, mercury and chlorinated solvents need to be
      considered. The current regulatory framework for PCDD/F-contaminated soil and for
      defining hazardous waste in the Russian Federation is not appropriate for the
      management of PCDD/F-contaminated sites. It is therefore suggested that a science
      based regulatory framework should be developed. The Russian Federation recently
      ratified the Stockholm Convention providing a foundation for the development of
      appropriate regulations and for further assessment, securing and remediation of
      the site. The impacts of pollution from the Khimprom plant demonstrate that the
      assessment and management of the organochlorine production sites should be a
      priority in the implementation of the Stockholm Convention by the Russian
      Federation and other countries.

PMID- 26201660
TI  - Characterization of particulate polycyclic aromatic hydrocarbons in an urban
      atmosphere of central-southern Spain.
AB  - Over 1-year period, 13 polycyclic aromatic hydrocarbons (PAHs) associated with
      particulate matter PM10 have been monitored for the first time in the atmosphere
      of Ciudad Real, situated at the central-southern Spain. PM10-bound PAHs were
      collected using a high-volume sampler from autumn 2012 to summer 2013 and were
      analyzed by HPLC with fluorescence detector. The most abundant PAHs were pyrene,
      chrysene, benzo[b]fluoranthene, dibenzo[a,h]anthracene and benzo[g,h,i]perylene.
      The ?PAH concentrations in Ciudad Real were 888, 368, 259 and 382 pg m(-3) for
      winter, spring, summer and autumn seasons, respectively. The diurnal variation of
      PAH was also investigated presenting the highest concentrations during the
      evening (19:00-23:00). Benzo[a]pyrene concentrations ranged from 2.4 to 110 pg m(
      3), these values are lower than the target value proposed by the European
      legislation, 1 ng m(-3). Diagnostic ratios were used to identify potential
      sources of PAHs. Results suggest that vehicle emissions are the major source of
      identified PAHs, with a higher contribution of diesel engines although other
      anthropogenic sources could also have an impact on the PAH levels.

PMID- 26201661
TI  - Effects of simulated acid rain on microbial characteristics in a lateritic red
      soil.
AB  - A laboratory experiment was performed to examine the impact of simulated acid
      rain (SAR) on nutrient leaching, microbial biomass, and microbial activities in a
      lateritic red soil in South China. The soil column leaching experiment was
      conducted over a 60-day period with the following six SAR pH treatments (levels):
      2.5, 3.0, 3.5, 4.0, 4.5, and 5.0 and one control treatment (pH = 7). Compared
      with the control treatment, the concentrations of soil organic matter, total
      nitrogen, total phosphorus, total potassium, soil microbial biomass carbon (MBC),
      soil microbial biomass nitrogen (MBN), and average well color density (AWCD) in
      the Ecoplates were all significantly decreased by leaching with SAR at different
      pH levels. The decrease in MBC and MBN indicated that acid rain reduced the soil
      microbial population, while the decrease in AWCD revealed that acid rain had a
      negative effect on soil bacterial metabolic function. Soil basal respiration
      increased gradually from pH 4.0 to 7.0 but decreased dramatically from pH 2.5 to
      3.0. The decrease in soil nutrient was the major reason for the change of soil
      microbial functions. A principal component analysis showed that the major carbon
      sources used by the bacteria were carbohydrates and carboxylic acids.

PMID- 26201662
TI  - Perchlorate reduction from a highly concentrated aqueous solution by bacterium
      Rhodococcus sp. YSPW03.
AB  - A novel isolated bacterium Rhodococcus sp. YSPW03 was able to reduce high
      concentrations (up to 700 mg L(-1)) of perchlorate using acetate as electron
      donor. Perchlorate reduction rate increased from 2.90 to 11.23 mg L(-1) h(-1)
      with increasing initial acetate concentration from 100 to 2000 mg L(-1), leading
      to complete removal of perchlorate (100 mg L(-1)) within 9 h. The bacterium also
      promoted complete reduction of high perchlorate concentrations (500 and 700 mg L(
      1)) at 2000 mg L(-1) of acetate within 48 and 96 h, respectively. Under semi
      continuous reactor operation, efficient reduction on varied perchlorate
      concentrations (80-700 mg L(-1)) was performed by the bacterium in presence of
      acetate (600-6000 mg L(-1)) over 140 days. The highest perchlorate reduction rate
      of 280 mg L(-1) day(-1) was observed with an initial perchlorate concentration of
      570 mg L(-1) at day 34. Dissolved chloride ions of 1000 mg L(-1) in the semi
      continuous reactor (SCR) completely inhibited the biological perchlorate
      reduction. The findings of this study will help improve the perchlorate
      bioreactor design and determine the optimal conditions to maximize the
      perchlorate reduction efficiency.

PMID- 26201663
TI  - Modeling of ammonia emission in the USA and EU countries using an artificial
      neural network approach.
AB  - Ammonia emissions at the national level are frequently estimated by applying the
      emission inventory approach, which includes the use of emission factors, which
      are difficult and expensive to determine. Emission factors are therefore the
      subject of estimation, and as such they contribute to inherent uncertainties in
      the estimation of ammonia emissions. This paper presents an alternative approach
      for the prediction of ammonia emissions at the national level based on artificial
      neural networks and broadly available sustainability and economical/agricultural
      indicators as model inputs. The Multilayer Perceptron (MLP) architecture was
      optimized using a trial-and-error procedure, including the number of hidden
      neurons, activation function, and a back-propagation algorithm. Principal
      component analysis (PCA) was applied to reduce mutual correlation between the
      inputs. The obtained results demonstrate that the MLP model created using the PCA
      transformed inputs (PCA-MLP) provides a more accurate prediction than the MLP
      model based on the original inputs. In the validation stage, the MLP and PCA-MLP
      models were tested for ammonia emission predictions for up to 2 years and
      compared with a principal component regression model. Among the three models, the
      PCA-MLP demonstrated the best performance, providing predictions for the USA and
      the majority of EU countries with a relative error of less than 20%.

PMID- 26201664
TI  - Homocysteine-Induced Endothelial Dysfunction.
AB  - This review discussed and in particular emphasis the potential cellular pathways
      and the biological processes involved that lead to homocysteine-induced
      endothelial dysfunction, in particular in the impaired endothelial dependent
      dilatation aspect. Hyperhomocysteinemia is an independent cardiovascular risk
      factor that has been associated with atherosclerotic vascular diseases and
      ischemic heart attacks. The potential mechanisms by which elevated plasma
      homocysteine level leads to reduction in nitric oxide bioavailability include the
      disruptive uncoupling of nitric oxide synthase activity and quenching of nitric
      oxide by oxidative stress, the enzymatic inhibition by asymmetric
      dimethylarginine, endoplasmic reticulum stress with eventual endothelial cell
      apoptosis, and chronic inflammation/prothrombotic conditions. Homocysteine
      induced endothelial dysfunction presumably affecting the bioavailability of the
      potent vasodilator 'nitric oxide', and such dysfunction can easily be monitor by
      flow-mediated dilation method using ultrasound. Understanding the mechanisms by
      which plasma homocysteine alter endothelial nitric oxide production is therefore
      essential in the comprehension of homocysteine-induced impairment of endothelial
      dependent dilatation, and its association of cardiovascular risk and its
      pathophysiology.

PMID- 26201665
TI  - Achieving Hand Hygiene Success With a Partnership Between Graduate Medical
      Education, Hospital Leadership, and Physicians.
AB  - Engaging physicians in hand hygiene programs is a challenge faced by many
      academic medical centers. Partnerships between education and academic leaders
      present opportunities for effective collaboration and improvement. The authors
      developed a robust hand hygiene quality improvement program, with attention to
      rapid-cycle improvements, including all levels of staff and health care
      providers. The program included a defined governance structure, clear data
      collection process, educational interventions, rapid-cycle improvements, and
      financial incentive for staff and physicians (including residents and fellows).
      Outcomes were measured on patients in all clinical areas. Run charts were used to
      document compliance in aggregate and by subgroups throughout the project
      duration. Institutional targets were achieved and then exceeded, with sustained
      hand hygiene compliance >90%. Physician compliance lagged behind aggregate
      compliance but ultimately was sustained at a level exceeding the target.
      Successfully achieving the institutional goal required collaboration among all
      stakeholders. Physician-specific data and physician champions were essential to
      drive improvement.

PMID- 26201666
TI  - Education and Imaging. Gastroenterology: Small bowel obstruction due to multiple
      spontaneous intramural duodenal hematomas.

PMID- 26201667
TI  - Education and Imaging. Gastroenterology: A unique endoscopic technique for full
      layer histology of jackhammer esophagus.

PMID- 26201668
TI  - Education and Imaging. Gastroenterology: Esophageal perforation in a patient with
      multiple myeloma- the 'bone' connection.

PMID- 26201669
TI  - Education and Imaging. Hepatobiliary and Pancreatic: Focal fatty infiltration of
      the liver mimicking malignancy in high-risk patients.

PMID- 26201670
TI  - Education and Imaging. Hepatobiliary and Pancreatic: Magnetic resonance imaging
      (MRI) features of liver involvement in adult-onset Still's disease.

PMID- 26201671
TI  - Clinical outcomes in patients with nonfunctioning pituitary adenomas managed
      conservatively.
AB  - CONTEXT: The natural history and the optimum management of patients with
      nonfunctioning pituitary adenomas (NFPAs) are unclear. OBJECTIVE: Our objective
      was to characterize the natural history of patients with NFPAs managed
      conservatively. DESIGN AND PATIENTS: We conducted a retrospective analysis of
      patients presenting to a tertiary referral centre between 1986 and 2009. Patients
      with pituitary adenomas and no clinical or biochemical evidence of hormonal
      hypersecretion were included. Those presenting with apoplexy or a radiological
      follow-up period of less than 1 year were excluded. The pituitary imaging for all
      patients was re-examined by two neuroradiologists in consensus. OUTCOME MEASURES:
      The outcome measures were change in tumour size and pituitary hormone function.
      RESULTS: Sixty-six patients were managed conservatively for a mean follow-up
      period of 4.3 years (range: 1-14.7). Forty-seven (71%) had a macroadenoma, and
      nineteen (29%) had a microadenoma. Tumour size decreased or remained stable in
      40% of macroadenomas and 47% of microadenomas. The median annual growth rate of
      enlarging macroadenomas and microadenomas was 1.0 mm/year and 0.4 mm/year,
      respectively. The median annual growth rate of macroadenomas was significantly
      higher than that of microadenomas (P < 0.01). Sixty-eight percentage of patients
      with a macroadenoma had pituitary hormone deficiency in one or more axes,
      compared to 42% of those with a microadenoma. CONCLUSION: Patients with NFPAs
      without optic chiasm compression can be managed conservatively. All patients need
      pituitary function assessment, irrespective of tumour size. These findings
      provide clinically relevant data for the management of patients with NFPAs.

PMID- 26201672
TI  - Neurovascular uncoupling in resting state fMRI demonstrated in patients with
      primary brain gliomas.
AB  - BACKGROUND: To demonstrate that the problem of brain tumor-related neurovascular
      uncoupling (NVU) is a significant issue with respect to resting state blood
      oxygen level dependent (BOLD) functional MRI (rsfMRI) similar to task-based BOLD
      fMRI, in which signal detectability can be compromised by breakdown of normal
      neurovascular coupling. METHODS: We evaluated seven de novo brain tumor patients
      who underwent resting state fMRI as part of comprehensive clinical fMRI exams at
      3 Tesla. For each of the seven patients who demonstrated evidence of NVU on task
      based motor fMRI, we performed both an independent component analysis (ICA) and
      an atlas-based parcellation-based seed correlation analysis (SCA) of the resting
      state fMRI data. For each patient, ipsilesional (IL) and contralesional (CL)
      regions of interest (ROIs) comprising primary motor and somatosensory cortices
      were used to evaluate BOLD signal changes on Z score maps derived from both ICA
      and SCA analysis for evidence of NVU. A subsequent two-tailed t-test was
      performed to determine whether statistically significant differences between the
      two sides were present that were consistent with NVU. RESULTS: In seven patients,
      overall decreased BOLD signal (based on suprathreshold voxels in ICA and SCA
      derived Z-score maps) was noted in IL compared with CL ROIs (P < 0.01),
      consistent with NVU. CONCLUSION: We have demonstrated that NVU can result in
      false negative BOLD signal changes on rsfMRI comparable to previously published
      findings on standard motor task-based fMRI.

PMID- 26201673
TI  - A review of sacral nerve stimulation for faecal incontinence following rectal
      surgery and radiotherapy.
AB  - AIM: Faecal incontinence may occur following rectal surgery and/or radiotherapy
      for rectal cancer. The aim of this paper was to review the evidence to support
      the use of sacral nerve stimulation (SNS) for patients with incontinence who had
      undergone rectal surgery or received rectal radiotherapy. METHOD: A search was
      performed of PubMed, Medline and Embase. All studies which reported the outcome
      of SNS in patients who had undergone a rectal resection or radiotherapy were
      reviewed. RESULTS: The first report of SNS following rectal surgery was in 2002.
      Since then seven further studies have described its effect in patients who have
      undergone anterior resection or pelvic radiotherapy. The total number of patients
      was 57. All studies were single group series, which ranged in size from one to 15
      patients. The follow-up ranged from 1 to 36 months. The success of peripheral
      nerve evaluation ranged from 47% to 100%. Permanent SNS improved the symptoms and
      in some studies this was reflected in improved quality of life. The wide
      variation of patient factors, operations performed, the dose of radiotherapy
      given and time from operation makes interpretation of the results difficult.
      CONCLUSION: Larger studies with better patient selection are needed to
      investigate the effect of SNS on incontinence following radiotherapy or rectal
      surgery.

PMID- 26201674
TI  - Glenoid version by CT scan: an analysis of clinical measurement error and
      introduction of a protocol to reduce variability.
AB  - OBJECTIVE: Recent studies have challenged the accuracy of conventional
      measurements of glenoid version. Variability in the orientation of the scapula
      from individual anatomical differences and patient positioning, combined with
      differences in observer measurement practices, have been identified as sources of
      variability. The purpose of this study was to explore the utility and reliability
      of clinically available software that allows manipulation of three-dimensional
      images in order to bridge the variance between clinical and anatomic version in a
      clinical setting. MATERIALS AND METHODS: Twenty CT scans of normal glenoids of
      patients who had proximal humerus fractures were measured for version. Four
      reviewers first measured version in a conventional manner (clinical version),
      measurements were made again (anatomic version) after employing a protocol for
      reformatting the CT data to align the coronal and sagittal planes with the
      superior-inferior axis of the glenoid, and the scapular body, respectively.
      RESULTS: The average value of clinical retroversion for all reviewers and all
      subjects was -1.4 degrees  (range, -16 degrees  to 21 degrees ), as compared to 
      3.2 degrees  (range, -21 degrees  to 6 degrees ) when measured from reformatted
      images. The mean difference between anatomical and clinical version was 1.9
      degrees  +/- 5.6 degrees  but ranged on individual measurements from -13 degrees 
      to 26 degrees . In no instance did all four observers choose the same image slice
      from the sequence of images. CONCLUSIONS: This study confirmed the variation in
      glenoid version dependent on scapular orientation previously identified in other
      studies using scapular models, and presents a clinically accessible protocol to
      correct for scapular orientation from the patient's CT data.

PMID- 26201675
TI  - Limited role of gadolinium to detect active sacroiliitis on MRI in juvenile
      spondyloarthritis.
AB  - OBJECTIVE: The aim of this study is to determine the added diagnostic value of
      contrast-enhanced (CE) magnetic resonance imaging (MRI) compared to routine non
      contrast-enhanced MRI to detect active sacroiliitis in clinically juvenile
      spondyloarthritis (JSpA). MATERIALS AND METHODS: A total of 80 children
      clinically suspected for sacroiliitis prospectively underwent MRI of the
      sacroiliac (SI) joints. Axial and coronal T1-weighted (T1), Short-tau inversion
      recovery (STIR) and fat-saturated T1-weighted gadolinium-DTPA (Gd) contrast
      enhanced (T1/Gd) sequences were obtained. The presence of bone marrow edema
      (BME), capsulitis, enthesitis, high intra-articular STIR signal, synovial
      enhancement and a global diagnostic impression of the MRI for diagnosis of
      sacroiliitis was recorded. RESULTS: STIR and T1/Gd sequences had 100% agreement
      for depiction of BME, capsulitis and enthesitis. High intra-articular STIR signal
      was seen in 18/80 (22.5%) patients, 15 (83%) of whom also showed synovial
      enhancement in the T1/Gd sequence. Sensitivity (SN) and specificity (SP) for a
      clinical diagnosis of JSpA were similar for high STIR signal (SN = 33%, SP = 85%)
      and T1/Gd synovial enhancement (SN = 36%, SP = 92%). Positive likelihood ratio
      (LR+) for JSpA was twice as high for synovial enhancement than high STIR signal
      (4.5 compared to 2.2). Global diagnostic impression was similar (STIR: SN = 55%,
      SP = 87%, LR + =4 .2; T1/Gd: SN = 55%, SP = 92%, LR + = 6.9). CONCLUSION: MRI
      without contrast administration is sufficient to identify bone marrow edema,
      capsulitis and retroarticular enthesitis as features of active sacroiliitis in
      juvenile spondyloarthritis. In selected cases when high STIR signal in the joint
      is the only finding, gadolinium-enhanced images may help to confirm the presence
      of synovitis.

PMID- 26201676
TI  - Metal artifact suppression at the hip: diagnostic performance at 3.0 T versus 1.5
      Tesla.
AB  - PURPOSE: This work aimed to compare the diagnostic performance of a metal
      artifact suppression sequence (MAVRIC-SL) for imaging of hip arthroplasties (HA)
      at 1.5 and 3 Tesla (T) field strength. METHODS: Eighteen patients (10 females;
      aged 27-74) with HA were examined at 3.0 and 1.5 T within 3 weeks. The sequence
      protocol included 3D-MAVRIC-SL PD (coronal), 3D-MAVRIC-SL STIR (axial), FSE T1,
      FSE PD and STIR sequences. Anatomical structures and pathological findings were
      assessed independently by two radiologists. Artifact extent and technical quality
      (image quality, fat saturation and geometric distortion) were also evaluated.
      Findings at 1.5 and 3.0 T were compared using a Wilcoxon signed rank test.
      RESULTS: While image quality was better at 1.5 T, visualization of anatomic
      structures and clinical abnormalities was not significantly different using the
      two field strengths (p > 0.05). Fat suppression and amount of artifacts were
      significantly better at 1.5 T (p  < 0.01). Inter- and intra-reader agreement for
      different anatomic details, image quality and visualization of abnormalities
      ranged from k = 0.62 to k = 1.00. CONCLUSION: MAVRIC-SL at 1.5 T had a comparable
      diagnostic performance when compared MAVRIC-SL at 3.0 T; however, the higher
      field strength was associated with larger artifacts, limited image quality and
      worse fat saturation.

PMID- 26201677
TI  - Graphene Plasmonic Metasurfaces to Steer Infrared Light.
AB  - Metasurfaces utilizing engineered metallic nanostructures have recently emerged
      as an important means to manipulate the propagation of light waves in a
      prescribed manner. However, conventional metallic metasurfaces mainly efficiently
      work in the visible and near-infrared regime, and lack sufficient tunability. In
      this work, combining the pronounced plasmonic resonance of patterned graphene
      structures with a subwavelength-thick optical cavity, we propose and demonstrate
      novel graphene metasurfaces that manifest the potential to dynamically control
      the phase and amplitude of infrared light with very high efficiency. It is shown
      that the phase of the infrared light reflected from a simple graphene ribbon
      metasurface can span over almost the entire 2pi range by changing the width of
      the graphene ribbons, while the amplitude of the reflection can be maintained at
      high values without significant variations. We successfully realize anomalous
      reflection, reflective focusing lenses, and non-diffracting Airy beams based on
      graphene metasurfaces. Our results open up a new paradigm of highly integrated
      photonic platforms for dynamic beam shaping and adaptive optics in the crucial
      infrared wavelength range. 

PMID- 26201679
TI  - Does laparoscopic shaving for deep infiltrating endometriosis alter intestinal
      function? A prospective study.
AB  - BACKGROUND: 5-12% of deep infiltrating endometriosis involves the digestive
      tract, especially the distal sigmoid colon and rectum. Bowel endometriosis
      surgery may be associated with neurological complications. AIM: The aim of this
      study was to objectively evaluate whether excision of rectosigmoid deep
      infiltrating endometriosis by shaving technique alters intestinal and defecatory
      function at 6-months post-surgery. MATERIALS AND METHODS: Nineteen women were
      enrolled in our tertiary care university hospital. They were affected by
      rectosigmoid endometriosis and underwent laparoscopic shaving excision of the
      nodule. Anorectal manometry was performed prior to and after surgery. The
      parameters studied were resting pressure, maximum squeezing pressure, pushing,
      rectoanal inhibitory reflex and rectal sensibility. The women completed a
      defecatory function questionnaire and ranked pain symptoms using a visual
      analogue scale. RESULTS: After surgery, no alteration of rectoanal inhibitory
      reflex was found. The tone of the internal anal sphincter was not significantly
      different before and after surgery. The defecatory function questionnaire
      revealed a significant improvement in constipation, urgency, bowel movements and
      anal eczema. No cases of incontinence were described. CONCLUSIONS: This report of
      the objective assessment of neurological intestinal alterations after rectal
      shaving of endometriotic nodules suggests the laparoscopic shaving technique
      preserves intestinal neurological activity.

PMID- 26201678
TI  - Motor Competence and its Effect on Positive Developmental Trajectories of Health.
AB  - In 2008, Stodden and colleagues took a unique developmental approach toward
      addressing the potential role of motor competence in promoting positive or
      negative trajectories of physical activity, health-related fitness, and weight
      status. The conceptual model proposed synergistic relationships among physical
      activity, motor competence, perceived motor competence, health-related physical
      fitness, and obesity with associations hypothesized to strengthen over time. At
      the time the model was proposed, limited evidence was available to support or
      refute the model hypotheses. Over the past 6 years, the number of investigations
      exploring these relationships has increased significantly. Thus, it is an
      appropriate time to examine published data that directly or indirectly relate to
      specific pathways noted in the conceptual model. Evidence indicates that motor
      competence is positively associated with perceived competence and multiple
      aspects of health (i.e., physical activity, cardiorespiratory fitness, muscular
      strength, muscular endurance, and a healthy weight status). However, questions
      related to the increased strength of associations across time and
      antecedent/consequent mechanisms remain. An individual's physical and
      psychological development is a complex and multifaceted process that
      synergistically evolves across time. Understanding the most salient factors that
      influence health and well-being and how relationships among these factors change
      across time is a critical need for future research in this area. This knowledge
      could aid in addressing the declining levels of physical activity and fitness
      along with the increasing rates of obesity across childhood and adolescence.

PMID- 26201681
TI  - Increasing Selenium and Yellow Pigment Concentrations in Foxtail Millet (Setaria
      italica L.) Grain with Foliar Application of Selenite.
AB  - Although addition of selenium (Se) is known to increase Se in crops, it is
      unclear whether exogenous Se is linked to nutritional and functional components
      in foxtail millet (Setaria italica L.). In this study, we examined the potential
      of increasing Se and yellow pigment (YP) in foxtail millet grain by foliar
      application of Se. Field experiments were conducted during the growing season of
      foxtail millet in 2013 and 2014 to assess the effects of foliar spray of sodium
      selenite (10-210 g Se ha(-1)) on the yield, Se uptake and accumulation, total YP,
      and microminerals in the grain. Average grain yields with Se application were
      5.60 and 4.53 t ha(-1) in the 2 years, showing no significant differences from
      the unfertilized control. However, grain Se concentration increased linearly with
      Se application rate, by 8.92 and 6.09 MUg kg(-1) in the 2 years with application
      of 1 g Se ha(-1) (maximum grain recovery rates of Se fertilizer, 52 and 28 %).
      Likewise, total grain YP concentration markedly increased by 0.038 and 0.031 mg
      kg(-1) in the 2 years with application of 1 g Se ha(-1). Grain Mn, Cu, Fe, and Zn
      concentrations were not significantly affected by Se application. This study
      indicated that foliar application of Se effectively and reliably increased the
      concentrations of Se and YP in foxtail millet grain without affecting the yield
      or mineral micronutrient concentrations. Thus, foliar-applied selenite has a
      significant potential to increase the concentrations of selenium and YP (putative
      lutein (Shen, J Cereal Sci 61:86-93, 2015; Abdel-Aal, Cereal Chem 79:455-457,
      2002; Abdel-Aal, J Agric Food Chem 55:787-794, 2007)) of foxtail millet and,
      thus, the health benefits of this crop. 

PMID- 26201682
TI  - Effects of Molybdenum or/and Cadmium on mRNA Expression Levels of Inflammatory
      Cytokines and HSPs in Duck Spleens.
AB  - Cadmium (Cd) and high dietary intake of molybdenum (Mo) can cause multiple-organ
      injury in animals, but the co-induced toxicity of Mo and Cd to spleen in ducks is
      not well understood. The aim of this study was to investigate the co-induced
      effects of Mo and Cd on the mRNA expression levels of inflammatory cytokines and
      heat shock proteins (HSPs) in duck spleens. Two hundred forty healthy 11-day-old
      ducks were randomly divided into six groups and treated with a commercial diet
      containing Mo or/and Cd. After being treated with Mo or/and Cd for 30, 60, 90,
      and 120 days, the mRNA expression levels of nuclear factor-kappa B (NF-kappaB),
      tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), HSP60, HSP70,
      and HSP90 were examined in duck spleens. Histopathology was examined in duck
      spleens at 120 days. The results indicated that the mRNA expression levels of
      HSPs were significantly upregulated in the co-induced groups (P < 0.01), while
      these decreased in the high dietary intake of Mo combined with Cd group at 120
      days. Exposure to Mo or/and Cd upregulated the mRNA expression levels of NF
      kappaB, COX-2, and TNF-alpha in the combination groups (P < 0.01). Furthermore,
      severe congestion, bleeding, splenic corpuscle structure fuzzy, wall thickness of
      sheath artery thickening, and oxyhematin were observed in the spleens of
      combination groups. Meanwhile, the organizational structure damage of the
      combined groups was more severe than that of the other groups. These results
      suggested that exposure to Mo or/and Cd might lead to tissue damage, and high
      expression of HSPs and inflammatory cytokines may play a role in the resistance
      of spleen toxicity induced by Mo or/and Cd. Interaction of Mo and Cd may have a
      synergistic effect on spleen toxicity. 

PMID- 26201683
TI  - Selective Life-Long Skeletal Myofiber-Targeted VEGF Gene Ablation Impairs
      Exercise Capacity in Adult Mice.
AB  - Exercise is dependent on adequate oxygen supply for mitochondrial respiration in
      both cardiac and locomotor muscle. To determine whether skeletal myofiber VEGF is
      critical for regulating exercise capacity, independent of VEGF function in the
      heart, ablation of the VEGF gene was targeted to skeletal myofibers (skmVEGF-/-)
      during embryogenesis (~ E9.5), leaving intact VEGF expression by all other cells
      in muscle. In adult mice, VEGF levels were decreased in the soleus (by 65%),
      plantaris (94%), gastrocnemius (74%), EDL (99%) and diaphragm (64%) (P < 0.0001,
      each muscle). VEGF levels were unchanged in the heart. Treadmill speed (WT 86 +/-
      4 cm/sec, skmVEGF-/- 70 +/- 5 cm/sec, P = 0.006) and endurance (WT 78 +/- 24 min,
      skmVEGF-/- 18 +/- 4 min, P = 0.0004) were severely limited in skmVEGF-/- mice in
      contrast to minor effect of conditional skmVEGF gene deletion in the adult. Body
      weight was also reduced (WT 22.8 +/- 1.6 g, skmVEGF-/-, 21.1 +/- 1.5, P = 0.02),
      but the muscle mass/body weight ratio was unchanged. The capillary/fiber ratio
      was lower in skmVEGF-/- plantaris (WT 1.51 +/- 0.12, skmVEGF-/- 1.16 +/- 0.20, P
      = 0.01), gastrocnemius (WT 1.61 +/- 0.08, skmVEGF-/- 1.39 +/- 0.08, P = 0.01),
      EDL (WT 1.36 +/- 0.07, skmVEGF-/- 1.14 +/- 0.13, P = 0.03) and diaphragm (WT 1.39
      +/-  0.18, skmVEGF-/- 0.79 +/- 0.16, P = 0.0001) but, not in soleus. Cardiac
      function (heart rate, maximal pressure, maximal dP/dt, minimal dP/dt,) in
      response to dobutamine was not impaired in anesthetized skmVEGF-/- mice. Isolated
      soleus and EDL fatigue times were 16% and 20% (P < 0.02) longer, respectively, in
      skmVEGF-/- mice than the WT group. These data suggest that skeletal myofiber VEGF
      expressed during development is necessary to establish capillary networks that
      allow maximal exercise capacity.

PMID- 26201684
TI  - Procedural sedation for MRI in children with ADHD.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common
      neurobehavioral disorder of childhood, affecting 5-8% of children. It has been
      observed that these children have poor sedation experiences; however, to date
      there is minimal research on procedural sedation in this population. AIM: To
      examine whether children with ADHD required larger doses of propofol for magnetic
      resonance imaging (MRI) sedation. METHODS: The hospital's administrative billing
      database was used to identify all billing codes for MRI brain scans (with and
      without contrast) in children aged between 5 and 12 years over the preceding 5.5
      years. The hospital's electronic medical record database provided baseline
      demographics. The sedation record was reviewed for propofol dose, psychostimulant
      use, and prescribed dose. All children received a standard weight-based dose of
      midazolam prior to receiving the necessary amount of propofol. Primary outcome
      was the dose of propofol administered (mg.kg(-1) ) to achieve adequate sedation.
      RESULTS: A total of 258 procedures met the inclusion criteria. The sample was 52%
      male, 74% White, 7.8% Black, 7.8% Hispanic, 4.3% Asian, and 6.2% other. ADHD was
      documented for 49 procedures with a prevalence of 18.5%. Patients with ADHD were
      older, more likely to be male, Hispanic, or to report race as 'Refused/Unknown'.
      Indications for MRI for patients with ADHD varied significantly, with
      'Behavioral' and 'Neurocutaneous' being significantly overrepresented in the ADHD
      group. The average sedative dose for all patients was 2.8 mg.kg(-1) (95% CI 2.62
      2.94). Sedative dose was similar among children with and without ADHD diagnosis.
      CONCLUSIONS: Our study illustrates that children with ADHD do not have higher
      sedative requirements to achieve a successful brain MRI.

PMID- 26201685
TI  - Lipopolysaccharide binding protein is an adipokine involved in the resilience of
      the mouse adipocyte to inflammation.
AB  - AIMS/HYPOTHESIS: Lipopolysaccharide (LPS) binding protein (LBP) is a novel 65 kDa
      adipokine, linked to adipose tissue (AT) inflammation, obesity and insulin
      resistance, that inhibits adipocyte differentiation. Here, we investigated the
      molecular mechanisms behind these detrimental effects on adipogenesis through
      whole-genome transcriptomics and in vitro experiments. METHODS: Permanent and
      transient knockdown (KD) and co-culture experiments were performed in 3T3-L1 and
      3T3-F442A cell lines during adipocyte differentiation. Microarray gene expression
      was performed using Genechip Affymetrix technology and validated by real-time
      PCR. RESULTS: LBP KD of 3T3-L1 cells led to a potentiated adipocyte
      differentiation with a dose-response relationship; genes involved in
      mitochondrial biogenesis, fatty acid metabolism and peroxisome proliferator
      activated receptor gamma (PPAR-gamma) action were dramatically upregulated in
      parallel to increased insulin signalling. Cells with LBP KD became refractory to
      proinflammatory cytokines and other inflammatory stimuli (LPS and palmitate).
      This phenotype, mediated through disrupted nuclear factor kappaB (NFkappaB)
      signalling, was reversed by a soluble factor present in a co-culture with native
      cells and by exogenous LBP. Double-silencing of LBP and toll-like receptor 4
      (TLR4) again rendered these cells insensitive to co-culture, LBP and inflammatory
      factors. CONCLUSIONS/INTERPRETATION: In summary, LBP is a proinflammatory soluble
      adipokine that acts as a brake for adipogenesis, strengthening the negative
      effects of palmitate and LPS on adipocyte differentiation.

PMID- 26201686
TI  - Incidence and risk factors for herpes zoster in patients undergoing liver
      transplantation.
AB  - BACKGROUND: Herpes zoster (HZ) is the most common manifestation of latent
      varicella zoster virus reactivation, which occurs naturally as a result of aging
      or in immunocompromised patients. Solid organ transplant recipients are at
      increased risk for HZ owing to their chronic immunosuppression. Although several
      reports investigated risk factors for the development of HZ in heart or renal
      transplantation, data in liver transplantation (LT) are limited. METHODS: We
      evaluated clinical data retrospectively in 377 adult patients undergoing LT
      between January 2005 and December 2012 in our institution. We analyzed the
      incidence rate of HZ and the standardized incidence ratio (SIR) by comparing with
      the general Japanese population. We additionally investigated risk factors for HZ
      after LT. RESULTS: HZ developed in 27 (7.16%) of the 377 patients after LT. The
      incidence rate of HZ after LT was 17.83 per 1000 person-years, which was
      significantly higher than in the general Japanese population (SIR = 4.61; 95%
      confidence interval [CI], 4.13-5.14). Multivariate analysis showed that older age
      (hazard ratio [HR] = 3.95; P < 0.001) and exposure to mycophenolate mofetil (HR =
      3.03; P = 0.007) were independent risk factors for HZ after LT. CONCLUSIONS: This
      is the first and largest study, to our knowledge, to investigate the incidence
      rate of HZ and risk factors for development of HZ after LT in the Japanese
      population. Further investigations to focus on immunosuppressive regimens to
      reduce the risk for HZ incidence in this high-risk population could establish a
      new protocol of immunosuppression after LT.

PMID- 26201687
TI  - Metaproteomics and metabolomics analyses of chronically petroleum-polluted sites
      reveal the importance of general anaerobic processes uncoupled with degradation.
AB  - Crude oil is one of the most important natural assets for humankind, yet it is a
      major environmental pollutant, notably in marine environments. One of the largest
      crude oil polluted areas in the word is the semi-enclosed Mediterranean Sea, in
      which the metabolic potential of indigenous microbial populations towards the
      large-scale chronic pollution is yet to be defined, particularly in anaerobic and
      micro-aerophilic sites. Here, we provide an insight into the microbial metabolism
      in sediments from three chronically polluted marine sites along the coastline of
      Italy: the Priolo oil terminal/refinery site (near Siracuse, Sicily), harbour of
      Messina (Sicily) and shipwreck of MT Haven (near Genoa). Using shotgun
      metaproteomics and community metabolomics approaches, the presence of 651
      microbial proteins and 4776 metabolite mass features have been detected in these
      three environments, revealing a high metabolic heterogeneity between the
      investigated sites. The proteomes displayed the prevalence of anaerobic
      metabolisms that were not directly related with petroleum biodegradation,
      indicating that in the absence of oxygen, biodegradation is significantly
      suppressed. This suppression was also suggested by examining the metabolome
      patterns. The proteome analysis further highlighted the metabolic coupling
      between methylotrophs and sulphate reducers in oxygen-depleted petroleum-polluted
      sediments. 

PMID- 26201688
TI  - Prolonged Exposure Therapy With Veterans and Active Duty Personnel Diagnosed With
      PTSD and Traumatic Brain Injury.
AB  - The present study used archival clinical data to analyze the delivery and
      effectiveness of prolonged exposure (PE) and ancillary services for posttraumatic
      stress disorder (PTSD) among Operation Enduring Freedom, Operation Iraqi Freedom,
      and Operation New Dawn veterans (N = 69) with histories of mild to severe
      traumatic brain injury (TBI). Data from standard clinical assessments of veterans
      and active duty personnel treated in both inpatient and outpatient programs at 2
      Department of Veteran Affairs medical centers were examined. Symptoms were
      assessed with self-report measures of PTSD (PTSD Checklist) and depression (Beck
      Depression Inventory-II) before and throughout therapy. Mixed linear models were
      utilized to determine the slope of reported symptoms throughout treatment, and
      the effects associated with fixed factors such as site, treatment setting
      (residential vs. outpatient), and TBI severity were examined. Results
      demonstrated significant decreases in PTSD, B = -3.00, 95% CI [-3.22, -2.78];
      t(210) = -13.5; p < .001, and in depressive symptoms, B = -1.46, 95% CI [-1.64, 
      1.28]; t(192) = -8.32; p < .001. The effects of PE treatment did not differ by
      clinical setting and participants with moderate to severe injuries reported more
      rapid gains than those with a history of mild TBI. The results provide evidence
      that PE may well be effective for veterans with PTSD and TBI.

PMID- 26201689
TI  - Coronary slow flow in the setting of Tako-tsubo cardiomyopathy: A causative
      factor? An innocent bystander? Or a prognostic sign?

PMID- 26201690
TI  - ATF3-dependent cross-talk between cardiomyocytes and macrophages promotes cardiac
      maladaptive remodeling.
AB  - RATIONALE: Pressure overload induces adaptive remodeling processes in the heart.
      However, when pressure overload persists, adaptive changes turn into maladaptive
      alterations leading to cardiac hypertrophy and heart failure. ATF3 is a stress
      inducible transcription factor that is transiently expressed following
      neuroendocrine stimulation. However, its role in chronic pressure overload
      dependent cardiac hypertrophy is currently unknown. OBJECTIVE: The objective of
      the study was to study the role of ATF3 in chronic pressure overload dependent
      cardiac remodeling processes. METHODS AND RESULTS: Pressure overload was induced
      by phenylephrine (PE) mini-osmotic pumps in various mice models of whole body,
      cardiac specific, bone marrow (BM) specific and macrophage specific ATF3
      ablations. We show that ATF3-KO mice exhibit a significantly reduced expression
      of cardiac remodeling markers following chronic pressure overload. Consistently,
      the lack of ATF3 specifically in either cardiomyocytes or BM derived cells blunts
      the hypertrophic response to PE infusion. A unique cross-talk between
      cardiomyocytes and macrophages was identified. Cardiomyocytes induce an ATF3
      dependent induction of an inflammatory response leading to macrophage recruitment
      to the heart. Adoptive transfer of wild type macrophages, but not ATF3-KO derived
      macrophages, into wild type mice potentiates maladaptive response to PE infusion.
      CONCLUSIONS: Collectively, this study places ATF3 as a key regulator in promoting
      pressure overload induced cardiac hypertrophy through a cross-talk between
      cardiomyocytes and macrophages. Inhibiting this cross-talk may serve as a useful
      approach to blunt maladaptive remodeling processes in the heart.

PMID- 26201691
TI  - Hereditary spastic paraplegia-linked REEP1 modulates endoplasmic
      reticulum/mitochondria contacts.
AB  - OBJECTIVE: Mutations in receptor expression enhancing protein 1 (REEP1) are
      associated with hereditary spastic paraplegias (HSPs). Although axonal
      degeneration is thought to be a predominant feature in HSP, the role of REEP1
      mutations in degeneration is largely unknown. Previous studies have implicated a
      role for REEP1 in the endoplasmic reticulum (ER), whereas others localized REEP1
      with mitochondria. We sought to resolve the cellular localization of REEP1 and
      further elucidate the pathobiology underlying REEP1 mutations in patients.
      METHODS: A combination of cellular imaging and biochemical approaches was used to
      refine the cellular localization of REEP1. Next, Reep1 mutations associated with
      HSP were functionally tested in neuritic growth and degeneration assays using
      mouse cortical culture. Finally, a novel assay was developed and used with wild
      type and mutant Reep1s to measure the interactions between the ER and
      mitochondria. RESULTS: We found that REEP1 is present at the ER-mitochondria
      interface, and it contains subdomains for mitochondrial as well as ER
      localization. Knockdown of Reep1 and expression of pathological Reep1 mutations
      resulted in neuritic growth defects and degeneration. Finally, using our novel
      split-RLuc8 assay, we show that REEP1 facilitates ER-mitochondria interactions, a
      function diminished by disease-associated mutations. INTERPRETATION: Our data
      potentially reconcile the current conflicting reports regarding REEP1 being
      either an ER or a mitochondrial protein. Furthermore, our results connect, for
      the first time, the disrupted ER-mitochondria interactions to a failure in
      maintaining health of long axons in HSPs. Finally, the split-RLuc8 assay offers a
      new tool to identify potential drugs for multiple neurodegenerative diseases with
      ER-mitochondria interaction defects.

PMID- 26201692
TI  - Predictors of Self-Reported Family Health History of Breast Cancer.
AB  - The objective of this study was to identify predictors of self-reported family
      health history of breast cancer in an ethnically diverse population of women
      participating in a breast cancer screening program. Participants completed a self
      administered questionnaire about their demography, health, breast health and
      family health history of breast cancer. The association between family health
      history of breast cancer and categorical variables were analyzed using the T
      test, chi square, and multi-nominal logistic regression. Those who were least
      likely to report a family history of cancer were African Americans (p = 0.02),
      and immigrant women from South America (p < 0.001) and Africa (p = 0.04).
      However, 34.4 % reported having a second-degree maternal relative with breast
      cancer compared to 6.9 % who reported having a second degree paternal relative
      with breast cancer. Therefore, there is a need to increase efforts to educate
      families about the importance of collecting and sharing one's family health
      history.

PMID- 26201693
TI  - Naringin induces autophagy-mediated growth inhibition by downregulating the
      PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells.
AB  - Naringin, one of the major bioflavonoid of Citrus, has been demonstrated as
      potential anticancer agent. However, the underlying anticancer mechanism still
      needs to be explored further. This study investigated the inhibitory effect of
      Naringin on human AGS cancer cells. AGS cell proliferation was inhibited by
      Naringin in a dose- and time-dependent manner. Naringin did not induce apoptotic
      cell death, determined by no DNA fragmentation and the reduced Bax/Bcl-xL ratio.
      Growth inhibitory role of Naringin was observed by western blot analysis
      demonstrating downregulation of PI3K/Akt/mTOR cascade with an upregulated
      p21CIPI/WAFI. Formation of cytoplasmic vacuoles and autophagosomes were observed
      in Naringin-treated AGS cells, further confirmed by the activation of autophagic
      proteins Beclin 1 and LC3B with a significant phosphorylation of mitogen
      activated protein kinases (MAPKs). Collectively, our observed results determined
      that anti-proliferative activity of Naringin in AGS cancer cells is due to
      suppression of PI3K/Akt/mTOR cascade via induction of autophagy with activated
      MAPKs. Thus, the present finding suggests that Naringin induced autophagy-
      mediated growth inhibition shows potential as an alternative therapeutic agent
      for human gastric carcinoma. 

PMID- 26201694
TI  - Effects of intraoperative administration of carbohydrates during long-duration
      oral and maxillofacial surgery on the metabolism of carbohydrates, proteins, and
      lipids.
AB  - PURPOSE: Insulin resistance in patients undergoing invasive surgery impairs
      glucose and lipid metabolism and increases muscle protein catabolism, which may
      result in delayed recovery and prolonged hospital stay. We examined whether
      intraoperative administration of carbohydrates during long-duration oral and
      maxillofacial surgery under general anesthesia affects carbohydrate, proteins,
      and lipid metabolism and the length of hospital stay. METHODS: We studied 16
      patients with normal liver, kidney, and endocrine functions, and ASA physical
      status I or II, but without diabetes. Patients were randomly assigned to receive
      0.1 g/kg/h of (n = 8) or lactated Ringer's solution (n = 8). Blood was collected
      before (T0) and 4 h after (T1) the start of surgery. We analyzed the plasma
      levels of glucose, ketone bodies, 3-methylhistidine (3-MH), and the length of
      hospital stay. RESULTS: At T0, no statistically significant differences were
      observed in the levels of glucose, ketone bodies, and 3-MH between the groups. At
      T1, no statistically significant difference in glucose levels was found between
      the groups. However, ketone bodies were significantly lower, and the changes in 3
      MH levels were significantly less pronounced in the glucose-treated group
      compared with controls. No significant differences were observed between the
      groups in terms of length of hospital stay. CONCLUSIONS: The administration of
      low doses of glucose during surgery was safe, did not cause hyperglycemia or
      hypoglycemia, and inhibited lipid metabolism and protein catabolism. Additional
      experiments with larger cohorts will be necessary to investigate whether
      intraoperative management with glucose facilitates postoperative recovery of
      patients with oral cancer.

PMID- 26201695
TI  - Physical meat quality and chemical composition of the Longissimus thoracis of
      entire and immunocastrated pigs fed varying dietary protein levels with and
      without ractopamine hydrochloride.
AB  - Physical and chemical attributes of the Longissimus thoracis (LT) of 96 PIC((c))
      entire (E) and immunocastrated (C) pigs were evaluated. The study followed a 2 *
      2 * 3 factorial design where three diets of low, medium and high proteins (7.50,
      9.79 and 12.07 g digestible lysine/kg) were fed either with (10mg/kg) or without
      ractopamine (RAC) for the last 28 days of growth. Vaccination of C occurred at 16
      and 20 weeks and slaughtering at 24 weeks of age. The LTs were analysed for
      moisture, protein, fat and ash contents as well as CIE L*, a*, b* colour, drip
      loss, cooking loss and Warner-Bratzler shear force (WBSF). Various sex and
      protein interactions were observed for LT protein content, L* values and WBSF.
      Cooking loss was decreased in C and by the medium protein diet. Feeding RAC
      increased WBSF values, whilst decreasing a* and b* values. However, the
      differences observed are minor and might be considered negligible when evaluated
      by a consumer.

PMID- 26201696
TI  - Integration of Omics Data in Genetic Epidemiology.

PMID- 26201697
TI  - Phenome-Wide Association Studies: Embracing Complexity for Discovery.
AB  - The inherent complexity of biological systems can be leveraged for a greater
      understanding of the impact of genetic architecture on outcomes, traits, and
      pharmacological response. The genome-wide association study (GWAS) approach has
      well-developed methods and relatively straight-forward methodologies; however,
      the bigger picture of the impact of genetic architecture on phenotypic outcome
      still remains to be elucidated even with an ever-growing number of GWAS
      performed. Greater consideration of the complexity of biological processes, using
      more data from the phenome, exposome, and diverse -omic resources, including
      considering the interplay of pleiotropy and genetic interactions, may provide
      additional leverage for making the most of the incredible wealth of information
      available for study. Here, we describe how incorporating greater complexity into
      analyses through the use of additional phenotypic data and widespread deployment
      of phenome-wide association studies may provide new insights into genetic factors
      influencing diseases, traits, and pharmacological response.

PMID- 26201698
TI  - Framework for the Integration of Genomics, Epigenomics and Transcriptomics in
      Complex Diseases.
AB  - OBJECTIVES: Different types of '-omics' data are becoming available in the post
      genome era; still a single -omics assessment provides limited insights to
      understand the biological mechanism of complex diseases. Genomics, epigenomics
      and transcriptomics data provide insight into the molecular dysregulation of
      neoplastic diseases, among them urothelial bladder cancer (UBC). Here, we propose
      a detailed analytical framework necessary to achieve an adequate integration of
      the three sets of -omics data to ultimately identify previously hidden genetic
      mechanisms in UBC. METHODS: We built a multi-staged framework to study possible
      pair-wise combinations and integrated the data in three-way relationships. SNP
      genotypes, CpG methylation levels and gene expression levels were determined for
      a total of 70 individuals with UBC and with fresh tumour tissue available.
      RESULTS: We suggest two main hypothesis-based scenarios for gene regulation based
      on the -omics integration analysis, where DNA methylation affects gene expression
      and genetic variants co-regulate gene expression and DNA methylation. We
      identified several three-way trans-association 'hotspots' that are found at the
      molecular level and that deserve further studies. CONCLUSIONS: The proposed
      integrative framework allowed us to identify relationships at the whole-genome
      level providing some new biological insights and highlighting the importance of
      integrating -omics data.

PMID- 26201699
TI  - Leveraging Epidemiologic and Clinical Collections for Genomic Studies of Complex
      Traits.
AB  - BACKGROUND/AIMS: Present-day limited resources demand DNA and phenotyping
      alternatives to the traditional prospective population-based epidemiologic
      collections. METHODS: To accelerate genomic discovery with an emphasis on diverse
      populations, we--as part of the Epidemiologic Architecture for Genes Linked to
      Environment (EAGLE) study--accessed all non-European American samples (n =
      15,863) available in BioVU, the Vanderbilt University biorepository linked to de
      identified electronic medical records, for genomic studies as part of the larger
      Population Architecture using Genomics and Epidemiology (PAGE) I study. Given
      previous studies have cautioned against the secondary use of clinically collected
      data compared with epidemiologically collected data, we present here a
      characterization of EAGLE BioVU, including the billing and diagnostic (ICD-9)
      code distributions for adult and pediatric patients as well as comparisons made
      for select health metrics (body mass index, glucose, HbA1c, HDL-C, LDL-C, and
      triglycerides) with the population-based National Health and Nutrition
      Examination Surveys (NHANES) linked to DNA samples (NHANES III, n = 7,159; NHANES
      1999-2002, n = 7,839). RESULTS: Overall, the distributions of billing and
      diagnostic codes suggest this clinical sample is a mixture of healthy and sick
      patients like that expected for a contemporary American population. CONCLUSION:
      Little bias is observed among health metrics, suggesting this clinical collection
      is suitable for genomic studies along with traditional epidemiologic cohorts.

PMID- 26201700
TI  - A Statistical Method for Identifying Trait-Associated Copy Number Variants.
AB  - Copy number variants (CNVs), ranging in size from about one kilobase to several
      megabases, are DNA alterations of a genome that result in the cell having less or
      more than two copies of segments of the DNA. Such CNVs have been shown to be
      associated with many complex phenotypes, ranging from diseases to gene
      expressions. Novel methods have been developed for identifying CNVs both at the
      individual and at the population level. However, methods for testing CNV
      association are limited. Most available methods employ a two-step approach, where
      CNVs carried by the samples are identified first and then tested for association.
      However, the results of such tests depend on the threshold used for CNV
      identification and also the number of CNVs to be tested. We developed a method,
      CNVtest, to directly identify the trait-associated CNVs without the need of
      identifying sample-specific CNVs. We show that CNVtest asymptotically controls
      the type I error rate and identifies true trait-associated CNVs with a high
      probability. We demonstrate the methods using simulations and an application to
      identify the CNVs that are associated with population differentiation.

PMID- 26201701
TI  - Model-Based Multifactor Dimensionality Reduction for Rare Variant Association
      Analysis.
AB  - Genome-wide association studies have revealed a vast amount of common loci
      associated to human complex diseases. Still, a large proportion of heritability
      remains unexplained. The extent to which rare genetic variants (RVs) are able to
      explain a relevant portion of the genetic heritability for complex traits leaves
      room for several debates and paves the way to the collection of RV databases and
      the development of novel analytic tools to analyze these. To date, several
      statistical methods have been proposed to uncover the association of RVs with
      complex diseases, but none of them is the clear winner in all possible scenarios
      of study design and assumed underlying disease model. The latter may involve
      differences in the distributions of effect sizes, proportions of causal variants,
      and ratios of protective to deleterious variants at distinct regions throughout
      the genome. Therefore, there is a need for robust scalable methods with
      acceptable overall performance in terms of power and type I error under various
      realistic scenarios. In this paper, we propose a novel RV association analysis
      strategy, which satisfies several of the desired properties that a RV analysis
      tool should exhibit.

PMID- 26201702
TI  - Multivariate Quantitative Multifactor Dimensionality Reduction for Detecting Gene
      Gene Interactions.
AB  - OBJECTIVES: To determine gene-gene interactions and missing heritability of
      complex diseases is a challenging topic in genome-wide association studies. The
      multifactor dimensionality reduction (MDR) method is one of the most commonly
      used methods for identifying gene-gene interactions with dichotomous phenotypes.
      For quantitative phenotypes, the generalized MDR or quantitative MDR (QMDR)
      methods have been proposed. These methods are known as univariate methods because
      they consider only one phenotype. To date, there are few methods for analyzing
      multiple phenotypes. METHODS: To address this problem, we propose a multivariate
      QMDR method (Multi-QMDR) for multivariate correlated phenotypes. We summarize the
      multivariate phenotypes into a univariate score by dimensional reduction
      analysis, and then classify the samples accordingly into high-risk and low-risk
      groups. We use different ways of summarizing mainly based on the principal
      components. Multi-QMDR is model-free and easy to implement. RESULTS: Multi-QMDR
      is applied to lipid-related traits. The properties of Multi- QMDR were
      investigated through simulation studies. Empirical studies show that Multi-QMDR
      outperforms existing univariate and multivariate methods at identifying causal
      interactions. CONCLUSIONS: The Multi-QMDR approach improves the performance of
      QMDR when multiple quantitative phenotypes are available.

PMID- 26201703
TI  - A Bagged, Partially Linear, Tree-Based Regression Procedure for Prediction and
      Variable Selection.
AB  - OBJECTIVES: In genomics, variable selection and prediction accounting for the
      complex interrelationships between explanatory variables represent major
      challenges. Tree-based methods are powerful alternatives to classical regression
      models. We have recently proposed the generalized, partially linear, tree-based
      regression (GPLTR) procedure that integrates the advantages of generalized linear
      regression (allowing the incorporation of confounding variables) and of tree
      based models. In this work, we use bagging to address a classical concern of tree
      based methods: their instability. METHODS: We present a bagged GPLTR procedure
      and three scores for variable importance. The prediction accuracy and the
      performance of the scores are assessed by simulation. The use of this procedure
      is exemplified by the analysis of a lung cancer data set. The aim is to predict
      the epidermal growth factor receptor (EGFR) mutation based on gene expression
      measurements, taking into account the ethnicity (confounder variable) and perform
      variable selection. RESULTS: The procedure performs well in terms of prediction
      accuracy. The scores differentiate predictive variables from noise variables.
      Based on a lung adenocarcinoma data set, the procedure achieves good predictive
      performance for EGFR mutation and selects relevant genes. CONCLUSION: The
      proposed bagged GPLTR procedure performs well for prediction and variable
      selection.

PMID- 26201704
TI  - Mendelian Randomization versus Path Models: Making Causal Inferences in Genetic
      Epidemiology.
AB  - OBJECTIVE: The term Mendelian randomization is popular in the current literature.
      The first aim of this work is to describe the idea of Mendelian randomization
      studies and the assumptions required for drawing valid conclusions. The second
      aim is to contrast Mendelian randomization and path modeling when different
      'omics' levels are considered jointly. METHODS: We define Mendelian randomization
      as introduced by Katan in 1986, and review its crucial assumptions. We introduce
      path models as the relevant additional component to the current use of Mendelian
      randomization studies in 'omics'. Real data examples for the association between
      lipid levels and coronary artery disease illustrate the use of path models.
      RESULTS: Numerous assumptions underlie Mendelian randomization, and they are
      difficult to be fulfilled in applications. Path models are suitable for
      investigating causality, and they should not be mixed up with the term Mendelian
      randomization. In many applications, path modeling would be the appropriate
      analysis in addition to a simple Mendelian randomization analysis. CONCLUSIONS:
      Mendelian randomization and path models use different concepts for causal
      inference. Path modeling but not simple Mendelian randomization analysis is well
      suited to study causality with different levels of 'omics' data.

PMID- 26201705
TI  - Clinical utilization of musculoskeletal sonography involving non-physician
      rehabilitation providers: a scoping review.
AB  - BACKGROUND: Musculoskeletal sonography use in point-of-care physical medicine and
      rehabilitation is rapidly expanding, not only by physiatrists, but also by non
      physician rehabilitation providers. AIM: The aim of the present review was to
      evaluate the current range, extent and nature of the related literature and to
      identify emerging areas of evidence for the use of musculoskeletal sonography
      involving non-physician rehabilitation providers to guide research and clinical
      practice. DESIGN: Scoping review. SETTING: Inpatient, outpatient, other.
      POPULATION: Musculoskeletal conditions. METHODS: Five databases were searched and
      578 unique abstracts were identified and screened for eligibility. Three raters
      independently read 68 full texts, and 36 articles that reported on applied uses
      of sonography by non-physician rehabilitation providers were included. RESULTS:
      Eighteen studies described direct clinical use, primarily for outcomes
      measurement (N.=12) or as a biofeedback intervention (N.=10). Twelve laboratory
      studies were included that related morphology to patient reports or validated
      clinical interventions. Six additional studies, although not involving non
      physician providers, were included as they presented potential valuable uses that
      were not noted in the other included studies, such as monitoring bone healing,
      tendon repair, and evaluation of idiopathic symptom reports or non-specific
      primary diagnoses. CONCLUSIONS: This review indicates that non-physician
      rehabilitation providers use sonography for outcomes measurement and biofeedback
      interventions. Research is needed to evaluate effects of these uses on patient
      outcomes and to explore additional potential uses for clinical reasoning,
      treatment planning, and monitoring of tissue healing related to intervention.
      CLINICAL REHABILITATION IMPACT: Implementation of musculoskeletal sonography by
      non-physician rehabilitation providers has the potential to be a critically
      advantageous addition to improve care.

PMID- 26201706
TI  - Comment: Mesoamerican nephropathy--new evidence and the need to act now.

PMID- 26201708
TI  - Proceedings of the 6th Danish Emergency Medicine Conference.

PMID- 26201707
TI  - Retraction Note: A novel polymorphism of the GP78 gene is associated with
      coronary artery disease in Han population in China.

PMID- 26201709
TI  - Integrated analysis of long-term safety in patients with chronic immune
      thrombocytopaenia (ITP) treated with the thrombopoietin (TPO) receptor agonist
      romiplostim.
AB  - A safety analysis of pooled data from clinical studies of romiplostim, a
      thrombopoietin (TPO) receptor agonist, in which patients with immune
      thrombocytopaenia (ITP) received romiplostim, placebo, or medical standard of
      care (SOC) Rodeghiero et al. (Eur J Haematol 91:423-436, 2013), has been updated.
      Included are data from 14 trials spanning 2002-2011; placebo- and SOC-arm data
      are pooled. Most patients (n = 1059) were female (61 %) and Caucasian (85 %); 38
      % had undergone splenectomy; 23 were children. Mean (SD) baseline platelet count
      was 20.6 (16.5) * 10(9)/L. Mean (SD) weekly dose of romiplostim was 4.2 (2.8)
      ug/kg; total exposure was 1520 patient-years. Overall, 921 patients received
      romiplostim only, 65 received placebo/SOC only, and 73 received placebo/SOC
      followed by romiplostim. Rates of haemorrhage (romiplostim, 205/100 patient
      years; placebo/SOC, 263/100), thrombosis (both, 5.5/100 patient-years),
      haematological malignancy/myelodysplastic syndrome (romiplostim, 0.5/100 patient
      years; placebo/SOC, 2.7/100), and non-haematological tumours (romiplostim,
      2.2/100 patient-years; placebo/SOC, 3.6/100) were comparable among groups. Bone
      marrow reticulin was reported in 17 patients and collagen in one patient
      receiving romiplostim; one patient receiving placebo/SOC had reticulin reported.
      Three patients developed neutralizing antibodies to romiplostim, but not to
      endogenous TPO. This integrated analysis of the safety profile of romiplostim in
      patients with ITP is consistent with previously reported studies; no new safety
      concerns emerged.

PMID- 26201710
TI  - Mild cognitive impairment in Parkinson's disease and vascular risk factors among
      Indian patients.

PMID- 26201711
TI  - Prenatal Screening of 21 Microdeletion/Microduplication Syndromes and
      Subtelomeric Imbalances by MLPA in Fetuses with Increased Nuchal Translucency and
      Normal Karyotype.
AB  - Fetuses with increased nuchal translucency thickness (NT) are at increased risk
      for chromosomal abnormalities. In case of a normal karyotype, a minority of them
      may present with structural abnormalities or genetic syndromes, which may be
      related to submicroscopic chromosomal imbalances. The objective of this study was
      to evaluate whether MLPA screening of 21 syndromic and subtelomeric regions could
      improve the detection rate of small chromosomal aberrations in fetuses with
      increased NT and a normal karyotype. A total of 106 prenatal samples from fetuses
      with NT >= 99th centile and normal R- and G-banding were analyzed by MLPA for
      subtelomeric imbalances (SALSA P036 and P070) and 21 syndromic regions (SALSA
      P245). One sample showed a benign CNV (dup(8)pter, FBXO25 gene), and 1 patient
      was found to have a loss of 18 qter and a gain of 5 pter as a result of an
      unbalanced translocation. The incidence of cryptic pathogenic variants was <1% or
      2.7% when only fetuses with other ultrasound abnormalities were taken into
      account. Submicroscopic imbalances in fetuses with increased NT may be
      individually rare, and genome-wide screening seems more likely to improve the
      diagnostic yield in these fetuses.

PMID- 26201712
TI  - Relationship between personality dimensions and medical specialty in 1661
      residents.

PMID- 26201713
TI  - Rifaximin vs. lactulose in treatment of minimal hepatic encephalopathy.
AB  - BACKGROUND & AIMS: Lactulose and rifaximin have already been shown to improve
      both cognitive functions and health related quality of life (HRQOL) in MHE
      patients. We aimed to compare the efficacy of rifaximin with lactulose in
      reversal of MHE and improvement in HRQOL in cirrhotic patients with MHE. METHOD:
      This prospective, randomized, open label, non-inferiority trial, was conducted at
      the Gastroenterology department of a tertiary care institute in Northern India.
      MHE was diagnosed if any two of the five neuro-psychometric (NP) tests were
      positive. HRQOL was assessed using the sickness impact profile (SIP)
      questionnaire (John Hopkins University, USA). RESULTS: Of 527 cirrhotics
      screened, 351 were found eligible and tested for MHE. A total of 112 (31.9%)
      patients were found to have MHE and then randomized into two groups group A
      (lactulose; 30-120 ml/day) and B (Tablet. rifaximin; 400 mg thrice a day). Based
      on the intention-to-treat population, the proportion of patients with MHE
      reversal at 3 months was 73.7% (42/57) in the rifaximin arm and 69.1% (38/55) in
      the lactulose arm [4.6% difference (90% CI -9.3% to 18.4%)]. However, non
      inferiority of rifaximin over lactulose could not be established as the pre
      specified non-inferiority margin (-5%) lies within the two-sided 90% confidence
      interval of the difference. HRQOL was significantly improved in both groups (P =
      0.20). However, the proportion of patients with flatulence (P = 0.004) and
      diarrhoea (P = 0.0002) was significantly higher in patients who took lactulose.
      CONCLUSION: Non-inferiority of rifaximin over lactulose for MHE reversal was not
      established.

PMID- 26201714
TI  - Equine infectious anaemia in Europe: Time to re-examine the efficacy of
      monitoring and control protocols?

PMID- 26201718
TI  - Non-sedation versus sedation with a daily wake-up trial in critically ill
      patients receiving mechanical ventilation--effects on physical function: study
      protocol for a randomized controlled trial: a substudy of the NONSEDA trial.
AB  - BACKGROUND: Critically ill patients rapidly loose much of their muscle mass and
      strength. This can be attributed to prolonged admission, prolonged mechanical
      ventilation and increased mortality, and it can have a negative impact on the
      degree of independence and quality of life. In the NONSEDA trial we randomize
      critically ill patients to non-sedation or sedation with a daily wake-up trial
      during mechanical ventilation in the intensive care unit. It has never been
      assessed whether non-sedation affects physical function. The aim of this study is
      to assess the effects of non-sedation versus sedation with a daily wake-up trial
      on physical function after discharge from intensive care unit. METHODS/DESIGN:
      Investigator-initiated, randomized, clinical, parallel-group, superiority trial,
      including 700 patients in total, with a substudy concerning 200 of these
      patients. Inclusion criteria will be intubated, mechanically ventilated patients
      with expected duration of mechanical ventilation >24 h. Exclusion criteria will
      be patients with severe head trauma, coma at admission or status epilepticus,
      patients treated with therapeutic hypothermia, patients with PaO2/FiO2<9 where
      sedation might be necessary to ensure sufficient oxygenation or placing the
      patient in a prone position. The experimental intervention will be non-sedation
      supplemented with pain management during mechanical ventilation. The control
      intervention will be sedation with a daily wake-up trial. The co-primary outcome
      will be quality of life regarding physical function (SF-36, physical component)
      and degree of independence in activities of daily living (Barthel Index), and
      this will be assessed for all 700 patients participating in the NONSEDA trial.
      The secondary outcomes, which will be assessed for the subpopulation of 200
      NONSEDA patients in the trial site, Kolding, will be 6-min walking distance,
      handgrip strength, muscle size (ultrasonographic measurement of the rectus
      femoris muscle cross-sectional area) and biomechanical data on lower extremity
      function (maximal voluntary contraction, rate of force development and
      endurance). DISCUSSION: This study is the first to investigate the effect of no
      sedation during critical illness on physical function. If an effect is found, it
      will add important information on how to prevent muscle weakness following
      critical illness. TRIAL REGISTRATION: The study has been approved by the relevant
      scientific ethics committee and is registered at ClinicalTrials.gov (ID:
      NCT02034942, 9 January 2014).

PMID- 26201719
TI  - Identification of novel target genes specifically activated by deregulated E2F in
      human normal fibroblasts.
AB  - The transcription factor E2F is the principal target of the tumor suppressor pRB.
      E2F plays crucial roles not only in cell proliferation by activating growth
      related genes but also in tumor suppression by activating pro-apoptotic and
      growth-suppressive genes. We previously reported that, in human normal
      fibroblasts, the tumor suppressor genes ARF, p27(Kip1) and TAp73 are activated by
      deregulated E2F activity induced by forced inactivation of pRB, but not by
      physiological E2F activity induced by growth stimulation. In contrast, growth
      related E2F targets are activated by both E2F activities, underscoring the roles
      of deregulated E2F in tumor suppression in the context of dysfunctional pRB. In
      this study, to further understand the roles of deregulated E2F, we explored new
      targets that are specifically activated by deregulated E2F using DNA microarray.
      The analysis identified nine novel targets (BIM, RASSF1, PPP1R13B, JMY, MOAP1,
      RBM38, ABTB1, RBBP4 and RBBP7), many of which are involved in the p53 and RB
      tumor suppressor pathways. Among these genes, the BIM gene was shown to be
      activated via atypical E2F-responsive promoter elements and to contribute to E2F1
      mediated apoptosis. Our results underscore crucial roles of deregulated E2F in
      growth suppression to counteract loss of pRB function. 

PMID- 26201720
TI  - Chemoprevention of Colonic Aberrant Crypt Foci by Novel Schiff Based Dichlorido(4
      Methoxy-2-{[2-(Piperazin-4-Ium-1-Yl)Ethyl]Iminomethyl}Phenolate)Cd Complex in
      Azoxymethane-Induced Colorectal Cancer in Rats.
AB  - Schiff-based complexes as a source of cancer chemotherapeutic compounds have been
      subjected to the variety of anticancer studies. The in-vitro analysis confirmed
      the CdCl2(C14H21N3O2) complex possess cytotoxicity and apoptosis induction
      properties in colon cancer cells, so lead to investigate the inhibitory
      efficiency of the compound on colonic aberrant crypt foci (ACF). Five groups of
      adult male rats were used in this study: Vehicle, cancer control, positive
      control groups and the groups treated with 25 and 50 mg/kg of complex for 10
      weeks. The rats in vehicle group were injected subcutaneously with 15 mg/kg of
      sterile normal saline once a week for 2 weeks and orally administered with 5%
      Tween-20 (5 ml/kg) for 10 weeks, other groups were injected subcutaneously with
      15 mg/kg azoxymethane once a week for 2 weeks. The rats in positive groups were
      injected intra-peritoneally with 35 mg/kg 5-Flourouracil four times in a month.
      Administration of the complex suppressed total colonic ACF formation up to 73.4%
      (P < 0.05). The results also showed that treatment with the complex significantly
      reduced the level of malondialdehyde while increasing superoxide dismutase and
      catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up
      regulation of Bax was confirmed by immunohistochemical staining. 

PMID- 26201721
TI  - Farm environment during infancy and lung function at the age of 31: a prospective
      birth cohort study in Finland.
AB  - OBJECTIVES: Farming as an occupation is considered a risk factor for asthma and
      reduced lung function. By contrast, living on a farm during infancy has been
      reported to be associated with lower risk of asthma in adulthood. However, little
      is known about the association between farming environment during infancy and
      lung function in adulthood. We aimed to study the prospective longitudinal
      association between farming environment during infancy and lung function in
      adulthood. DESIGN: A prospective birth cohort study. SETTING: Northern Finland.
      PARTICIPANTS: 5666 participants born in 1966 were followed up at the age of 31
      years. PRIMARY OUTCOME MEASURES: Spirometry at the age of 31 years. RESULTS: To
      be born into a farmer's family was associated with higher forced expiratory
      volume in 1 s (FEV1) (36 mL; 95% CI 6 to 67 mL) and forced vital capacity (FVC)
      (40 mL; 95% CI 5 to 75 mL) at the age of 31 years. Contact with farm animals
      during infancy was associated with higher FEV1. No associations were seen with
      FEV1/FVC (FEV1/FVC ratio). Having dogs in childhood revealed similar
      associations. There was a suggestive dose-dependent association with the number
      of animal species during childhood and higher FEV1 and FVC at adulthood,
      especially among women. CONCLUSIONS: Farming environment in early life may have a
      positive impact on lung function in adulthood.

PMID- 26201722
TI  - Non-invasive prenatal diagnosis using fetal DNA in maternal plasma: a preliminary
      study for identification of paternally-inherited alleles using single nucleotide
      polymorphisms.
AB  - OBJECTIVES: Single nucleotide polymorphism (SNP) with a mutation can be used to
      identify the presence of the paternally-inherited wild-type or mutant allele as
      result of the inheritance of either allele in the fetus and allows the prediction
      of the fetal genotype. This study aims to identify paternal SNPs located at the
      flanking regions upstream or downstream from the beta-globin gene mutations at
      CD41/42 (HBB:c.127_130delCTTT), IVS1-5 (HBB:c.92+5G>C) and IVS2-654 (HBB:c.316
      197C>T) using free-circulating fetal DNA. SETTING: Haematology Lab, Department of
      Biomedical Science, University of Malaya. PARTICIPANTS: Eight couples
      characterised as beta-thalassaemia carriers where both partners posed the same
      beta-globin gene mutations at CD41/42, IVS1-5 and IVS2-654, were recruited in
      this study. OUTCOME MEASURES: Genotyping was performed by allele specific-PCR and
      the locations of SNPs were identified after sequencing alignment. RESULTS:
      Genotype analysis revealed that at least one paternal SNP was present for each of
      the couples. Amplification on free-circulating DNA revealed that the paternal
      mutant allele of SNP was present in three fcDNA. Thus, the fetuses may be beta
      thalassaemia carriers or beta-thalassaemia major. Paternal wild-type alleles of
      SNP were present in the remaining five fcDNA samples, thus indicating that the
      fetal genotypes would not be homozygous mutants. CONCLUSIONS: This preliminary
      research demonstrates that paternal allele of SNP can be used as a non-invasive
      prenatal diagnosis approach for at-risk couples to determine the beta
      thalassaemia status of the fetus.

PMID- 26201723
TI  - 'You are just left to get on with it': qualitative study of patient and carer
      experiences of the transition to secondary progressive multiple sclerosis.
AB  - OBJECTIVES: Although the transition to secondary progressive multiple sclerosis
      (SPMS) is known to be a period of uncertainty for clinicians, who may find
      progressive disease challenging to objectively identify, little research has
      explored the experiences of patients and carers specifically during this
      transition period. Our objective was to explore what patients and their carers
      understand about their disease stage and describe their experiences and
      perspectives on the transition to SPMS. DESIGN: Semistructured qualitative
      interviews and subsequent validation focus groups were analysed using inductive
      thematic analysis. SETTING: South East Wales, UK. PARTICIPANTS: 20 patients with
      MS and 13 carers were interviewed. Eight patients and two carers participated in
      focus groups. RESULTS: Four main themes around disease progression were
      identified. 'Realisation' describes how patients came to understand they had SPMS
      while 'reaction' describes their response to this realisation. The 'realities' of
      living with SPMS, including dealing with the healthcare system during this
      period, were described along with 'future challenges' envisaged by patients and
      carers. CONCLUSIONS: Awareness that the transition to SPMS has occurred, and
      subsequent emotional reactions and coping strategies, varied widely between
      patients and their carers. The process of diagnosing the transition was often not
      transparent and some individuals wanted information to help them understand what
      the transition to SPMS meant for them.

PMID- 26201724
TI  - Supramitral membrane mimicking posterior mitral valve prolapse.

PMID- 26201725
TI  - Small lymphocytic lymphoma with florid perniosis-like features: a case report.
AB  - BACKGROUND: Small lymphocytic lymphoma is a relatively rare B-cell non-Hodgkin
      lymphoma that is considered to be the tissue equivalent of the much more common
      entity chronic lymphocytic leukemia. Cutaneous manifestations of small
      lymphocytic lymphoma are infrequent and the literature regarding them sparse. We
      describe here a case of a patient with a history of small lymphocytic lymphoma
      who developed perniosis-like features of the digits. CASE PRESENTATION: An 86
      year old male patient with previously diagnosed small lymphocytic lymphoma
      developed painful erythematous swelling of the periungual area of his fingers and
      toes. This was associated with a dense dermal infiltration of CD5-positive B
      lymphoid cells consistent with his low-grade B-cell lymphoma. Although partially
      refractory to local radiotherapy, the painful swelling of the fingers and toes
      resolved fully following systemic therapy with chlorambucil and rituximab.
      CONCLUSIONS: This unusual cutaneous manifestation of a lymphoma and the
      favourable response to systemic therapy may be instructive for the management of
      other patients who develop similar perniosis-like features.

PMID- 26201727
TI  - Stretching the comfort zone.

PMID- 26201726
TI  - What is the impact of interventions that prevent fetal mortality on the increase
      of preterm live births in the State of Sao Paulo, Brazil?
AB  - BACKGROUND: There is a global growing trend of preterm births and a decline trend
      of fetal deaths. Is there an impact of the decline of fetal mortality on the
      increase of preterm live births in State of Sao Paulo, Brazil? METHODS: The time
      trends were evaluated by gestational age through exponential regression analysis.
      Data analyzed included the fetal mortality ratio, proportion of preterm live
      births, fertility rate of women 35 years and over, prenatal care, mother's
      education, multiple births and cesarean section deliveries. A survival analysis
      was carried out for 2000 and 2010. RESULTS: Preterm births showed the highest
      annual increase (3.2%) in the less than 28 weeks of gestation group and fetal
      mortality ratio decreased (7.4%) in the same gestational age group. There was an
      increase of cesarean section births and it was higher in the < 28 weeks group
      (6.1%). There was a decreased annual trend of mothers with inadequate prenatal
      care (6.1%) and low education (8.8%) and an increased trend in multiple births
      and fertility rates of women of 35 years and over. The variables were highly
      correlated to which other over time. In 2000, 8.2% of all pregnancies resulted in
      preterm births (0.9% in fetal deaths and 7.3% in live births). In 2010, the
      preterm birth increased to 9.4% (0.8% were preterm fetal deaths and 8.6% preterm
      live births). CONCLUSIONS: The results suggest that 45.2% could be the maximum
      contribution of successful interventions to prevent a fetal death on the increase
      in preterm live births. This increasing trend is also related to changes of the
      women reproductive profile with the change of the women reproductive profile and
      access to prenatal care.

PMID- 26201733
TI  - Perovskite solar cells: Brighter pieces of the puzzle.

PMID- 26201734
TI  - Synthetic biology: Six pack and stack.

PMID- 26201735
TI  - Cheminformatics: Computing target complexity.

PMID- 26201736
TI  - Charge transfer: Interfering with interference.

PMID- 26201737
TI  - On-surface generation and imaging of arynes by atomic force microscopy.
AB  - Reactive intermediates are involved in many chemical transformations. However,
      their characterization is a great challenge because of their short lifetimes and
      high reactivities. Arynes, formally derived from arenes by the removal of two
      hydrogen atoms from adjacent carbon atoms, are prominent reactive intermediates
      that have been hypothesized for more than a century. Their rich chemistry enables
      a widespread use in synthetic chemistry, as they are advantageous building blocks
      for the construction of polycyclic compounds that contain aromatic rings. Here,
      we demonstrate the generation and characterization of individual polycyclic aryne
      molecules on an ultrathin insulating film by means of low-temperature scanning
      tunnelling microscopy and atomic force microscopy. Bond-order analysis suggests
      that a cumulene resonance structure is the dominant one, and the aryne reactivity
      is preserved at cryogenic temperatures. Our results provide important insights
      into the chemistry of these elusive intermediates and their potential application
      in the field of on-surface synthesis. 

PMID- 26201738
TI  - Sub-50-fs photoinduced spin crossover in [Fe(bpy)3]2+.
AB  - It is known that excitation by visible light of the singlet metal-to-ligand
      charge-transfer ((1)MLCT) states of Fe(II) complexes leads to population of the
      lowest-lying high-spin quintet state ((5)T) with unity quantum yield. Here we
      investigate this so-called spin crossover (SCO) transition in aqueous
      iron(II)tris(bipyridine). We use pump-probe transient absorption spectroscopy
      with a high time resolution of <60 fs in the ultraviolet probe range, in which
      the (5)T state absorbs, and of <40 fs in the visible probe range, in which both
      the hot MLCT state and the (5)T state absorb. Our results show that the (5)T
      state is impulsively populated in less than 50 fs, which is the time we measured
      for the depopulation of the MCLT manifold. We propose that non-totally-symmetric
      modes mediate the process, possibly high-frequency modes of the bipyridine (bpy)
      ligand. These results show that even though the SCO process in Fe(II) complexes
      represents a strongly spin-forbidden (DeltaS = 2) two-electron transition, spin
      flipping occurs at near subvibrational times and is intertwined with the electron
      and structural dynamics of the system. 

PMID- 26201739
TI  - Photoinduced reversible switching of porosity in molecular crystals based on star
      shaped azobenzene tetramers.
AB  - The development of solid materials that can be reversibly interconverted by light
      between forms with different physico-chemical properties is of great interest for
      separation, catalysis, optoelectronics, holography, mechanical actuation and
      solar energy conversion. Here, we describe a series of shape-persistent
      azobenzene tetramers that form porous molecular crystals in their E
      configuration, the porosity of which can be tuned by changing the peripheral
      substituents on the molecule. Efficient E->Z photoisomerization of the azobenzene
      units takes place in the solid state and converts the crystals into a non-porous
      amorphous melt phase. Crystallinity and porosity are restored upon Z->E
      isomerization promoted by visible light irradiation or heating. We demonstrate
      that the photoisomerization enables reversible on/off switching of optical
      properties such as birefringence as well as the capture of CO2 from the gas
      phase. The linear design, structural versatility and synthetic accessibility make
      this new family of materials potentially interesting for technological
      applications. 

PMID- 26201740
TI  - Diels-Alderase-free, bis-pericyclic, [4+2] dimerization in the biosynthesis of
      (+/-)-paracaseolide A.
AB  - The natural product paracaseolide A is a tetracyclic dilactone containing six
      adjacent stereocentres. Its skeleton occupies a unique structural space among the
      >200,000 characterized secondary metabolites. Six different research groups have
      reported a chemical synthesis of this compound, five of which used a thermal, net
      Diels-Alder [4+2] cycloaddition and dehydration at 110  degrees C to access the
      target by dimerization of a simple butenolide precursor. Here, we report that
      this dimerization proceeds under much milder conditions and with a different
      stereochemical outcome than previously recognized. This can be rationalized by
      invoking a bis-pericyclic transition state. Furthermore, we find that spontaneous
      epimerization, necessary to correct the configuration at one key stereocentre, is
      viable and that natural paracaseolide A is racemic. Together, these facts point
      to the absence of enzymatic catalysis (that is, Diels-Alderase activity) in the
      cycloaddition and strongly suggest that a non-enzyme-mediated dimerization is the
      actual event by which paracaseolide A is produced in nature. 

PMID- 26201741
TI  - Light-controlled self-assembly of non-photoresponsive nanoparticles.
AB  - The ability to guide the assembly of nanosized objects reversibly with external
      stimuli, in particular light, is of fundamental importance, and it contributes to
      the development of applications as diverse as nanofabrication and controlled drug
      delivery. However, all the systems described to date are based on nanoparticles
      (NPs) that are inherently photoresponsive, which makes their preparation
      cumbersome and can markedly hamper their performance. Here we describe a
      conceptually new methodology to assemble NPs reversibly using light that does not
      require the particles to be functionalized with light-responsive ligands. Our
      strategy is based on the use of a photoswitchable medium that responds to light
      in such a way that it modulates the interparticle interactions. NP assembly
      proceeds quantitatively and without apparent fatigue, both in solution and in
      gels. Exposing the gels to light in a spatially controlled manner allowed us to
      draw images that spontaneously disappeared after a specific period of time. 

PMID- 26201742
TI  - Enzymatic hydroxylation of an unactivated methylene C-H bond guided by molecular
      dynamics simulations.
AB  - The hallmark of enzymes from secondary metabolic pathways is the pairing of
      powerful reactivity with exquisite site selectivity. The application of these
      biocatalytic tools in organic synthesis, however, remains under-utilized due to
      limitations in substrate scope and scalability. Here, we report how the
      reactivity of a monooxygenase (PikC) from the pikromycin pathway is modified
      through computationally guided protein and substrate engineering, and applied to
      the oxidation of unactivated methylene C-H bonds. Molecular dynamics and quantum
      mechanical calculations were used to develop a predictive model for substrate
      scope, site selectivity and stereoselectivity of PikC-mediated C-H oxidation. A
      suite of menthol derivatives was screened computationally and evaluated through
      in vitro reactions, where each substrate adhered to the predicted models for
      selectivity and conversion to product. This platform was also expanded beyond
      menthol-based substrates to the selective hydroxylation of a variety of substrate
      cores ranging from cyclic to fused bicyclic and bridged bicyclic compounds. 

PMID- 26201743
TI  - Quantum interference between H + D2 quasiclassical reaction mechanisms.
AB  - Interferences are genuine quantum phenomena that appear whenever two seemingly
      distinct classical trajectories lead to the same outcome. They are common in
      elastic scattering but are seldom observable in chemical reactions. Here we
      report experimental measurements of the state-to-state angular distribution for
      the H + D2 reaction using the 'photoloc' technique. For products in low
      rotational and vibrational states, a characteristic oscillation pattern governs
      backward scattering. The comparison between the experiments, rigorous quantum
      calculations and classical trajectories on an accurate potential energy surface
      allows us to trace the origin of that structure to the quantum interference
      between different quasiclassical mechanisms, a phenomenon analogous to that
      observed in the double-slit experiment. 

PMID- 26201744
TI  - An oxazetidine amino acid for chemical protein synthesis by rapid, serine-forming
      ligations.
AB  - Amide-forming ligation reactions allow the chemical synthesis of proteins by the
      union of unprotected peptide segments, and enable the preparation of protein
      derivatives not accessible by expression or bioengineering approaches. The native
      chemical ligation (NCL) of thioesters and N-terminal cysteines is unquestionably
      the most successful approach, but is not ideal for all synthetic targets. Here we
      describe the synthesis of an Fmoc-protected oxazetidine amino acid for use in the
      alpha-ketoacid-hydroxylamine (KAHA) amide ligation. When incorporated at the N
      terminus of a peptide segment, this four-membered cyclic hydroxylamine can be
      used for rapid serine-forming ligations with peptide alpha-ketoacids. This
      ligation operates at low concentration (100 MUM-5 mM) and mild temperatures (20
      25  degrees C). The utility of the reaction was demonstrated by the synthesis of
      S100A4, a 12 kDa calcium-binding protein not easily accessible by NCL or other
      amide-forming reactions due to its primary sequence and properties. 

PMID- 26201746
TI  - Magically magnetic gadolinium.

PMID- 26201745
TI  - Optimization of a whole-cell biocatalyst by employing genetically encoded product
      sensors inside nanolitre reactors.
AB  - Microcompartmentalization offers a high-throughput method for screening large
      numbers of biocatalysts generated from genetic libraries. Here we present a
      microcompartmentalization protocol for benchmarking the performance of whole-cell
      biocatalysts. Gel capsules served as nanolitre reactors (nLRs) for the
      cultivation and analysis of a library of Bacillus subtilis biocatalysts. The B.
      subtilis cells, which were co-confined with E. coli sensor cells inside the nLRs,
      converted the starting material cellobiose into the industrial product vitamin
      B2. Product formation triggered a sequence of reactions in the sensor cells: (1)
      conversion of B2 into flavin mononucleotide (FMN), (2) binding of FMN by a RNA
      riboswitch and (3) self-cleavage of RNA, which resulted in (4) the synthesis of a
      green fluorescent protein (GFP). The intensity of GFP fluorescence was then used
      to isolate B. subtilis variants that convert cellobiose into vitamin B2 with
      elevated efficiency. The underlying design principles of the assay are general
      and enable the development of similar protocols, which ultimately will speed up
      the optimization of whole-cell biocatalysts. 

PMID- 26201747
TI  - Synergistic High Charge-Storage Capacity for Multi-level Flexible Organic Flash
      Memory.
AB  - Electret and organic floating-gate memories are next-generation flash storage
      mediums for printed organic complementary circuits. While each flash memory can
      be easily fabricated using solution processes on flexible plastic substrates,
      promising their potential for on-chip memory organization is limited by
      unreliable bit operation and high write loads. We here report that new
      architecture could improve the overall performance of organic memory, and
      especially meet high storage for multi-level operation. Our concept depends on
      synergistic effect of electrical characterization in combination with a polymer
      electret (poly(2-vinyl naphthalene) (PVN)) and metal nanoparticles (Copper). It
      is distinguished from mostly organic nano-floating-gate memories by using the
      electret dielectric instead of general tunneling dielectric for additional charge
      storage. The uniform stacking of organic layers including various dielectrics and
      poly(3-hexylthiophene) (P3HT) as an organic semiconductor, followed by thin-film
      coating using orthogonal solvents, greatly improve device precision despite easy
      and fast manufacture. Poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)]
      as high-k blocking dielectric also allows reduction of programming voltage. The
      reported synergistic organic memory devices represent low power consumption, high
      cycle endurance, high thermal stability and suitable retention time, compared to
      electret and organic nano-floating-gate memory devices. 

PMID- 26201748
TI  - Effect of Static Compressive Strain, Anisotropy, and Tissue Region on the
      Diffusion of Glucose in Meniscus Fibrocartilage.
AB  - Osteoarthritis (OA) is a significant socio-economic concern, affecting millions
      of individuals each year. Degeneration of the meniscus of the knee is often
      associated with OA, yet the relationship between the two is not well understood.
      As a nearly avascular tissue, the meniscus must rely on diffusive transport for
      nutritional supply to cells. Therefore, quantifying structure-function relations
      for transport properties in meniscus fibrocartilage is an important task. The
      purpose of the present study was to determine how mechanical loading, tissue
      anisotropy, and tissue region affect glucose diffusion in meniscus
      fibrocartilage. A one-dimensional (1D) diffusion experiment was used to measure
      the diffusion coefficient of glucose in porcine meniscus tissues. Results show
      that glucose diffusion is strain-dependent, decreasing significantly with
      increased levels of compression. It was also determined that glucose diffusion in
      meniscus tissues is anisotropic, with the diffusion coefficient in the
      circumferential direction being significantly higher than that in the axial
      direction. Finally, the effect of tissue region was not statistically
      significant, comparing axial diffusion in the central and horn regions of the
      tissue. This study is important for better understanding the transport and
      nutrition-related mechanisms of meniscal degeneration and related OA in the knee.

PMID- 26201749
TI  - Negative and positive life changes following treatment completion: Chinese breast
      cancer survivors' perspectives.
AB  - PURPOSE: Although we acknowledge the negative and positive aspects of the cancer
      survivorship experience, we have little information on this issue from the
      perspective of Chinese breast cancer survivors. This study aimed to explore the
      perceptions of negative and positive life changes following treatment completion
      among this population. METHODS: Using purposive sampling, 29 breast cancer
      survivors were selected from the attendees of a local cancer self-help
      organization in middle China and proceeded with semi-structured in-depth
      interviews. Each interview was transcribed verbatim and analyzed using directed
      content analysis. RESULTS: Two predetermined categories were identified to
      represent participant perception of the breast cancer survivorship experience,
      namely, negative life changes and positive life changes. The first category
      included fear of recurrence, symptom experience, poor body image, altered
      sexuality and intimacy, and financial burden. The second category consisted of
      new life perspective, personal growth, and enhanced relationships with family.
      CONCLUSIONS: Our findings contribute to the emerging evidence on the duality of
      breast cancer survivorship. This enhanced understanding of the specific negative
      and positive changes experienced by Chinese breast cancer survivors can assist
      health professionals in addressing survivorship issues by designing appropriate
      interventions to minimize negative consequences and enhance positive growth.

PMID- 26201750
TI  - Improving cancer patients' knowledge about totally implantable access port: a
      randomized controlled trial.
AB  - PURPOSE: Providing patients with written information about totally implantable
      access ports (TIAPs) is recommended during the pre-implantation period to reduce
      anxiety and to help recalling information. No study tested the effectiveness of
      information about TIAP neither with oral communication nor with booklets. This
      study aimed at evaluating the effectiveness of an information booklet, alone or
      together with answers to clarification questions, both in improving patients'
      short- and long-time knowledge about TIAP and in decreasing patients'
      physiological indicators of anxiety immediately after TIAP implantation. METHODS:
      This is a randomized controlled trial with three parallel groups: group A (n =
      34) receiving only the booklet, group B (n = 34) receiving the booklet with
      answers to clarification questions, and group C (n = 37) receiving routine care.
      RESULTS: After 3 months, pair comparisons revealed a significant improvement in
      knowledge of TIAP in each group (p < 0.001), together with a significant
      difference in group C compared with groups A (p < 0.001) and B (p < 0.001),
      similar to each other. Physiological indicators of anxiety decreased in the
      intervention groups compared to control group immediately after TIAP
      implantation. CONCLUSIONS: The interventions provided resulted effective in
      decreasing patients' physiological indicators of anxiety immediately after TIAP
      implantation and improving patients' knowledge about TIAP immediately and at 3
      months. Adding answers to clarification questions to the booklet was not more
      effective than the booklet alone. A well-designed booklet with attention both to
      scientific content and to communication techniques is useful in improving
      patients' knowledge about TIAP and reducing anxiety.

PMID- 26201751
TI  - Associations between caregiving worries and psychophysical well-being. An
      investigation on home-cared cancer patients family caregivers.
AB  - PURPOSE: Caregiving to a family member with cancer might have health
      implications. However, limited research has investigated the psychophysical
      health of home-cared cancer patients family caregivers. In a previous study, we
      have found that a prolonged worry in daily life is a crucial variable compared to
      caregivers' psychophysical symptomatology. This investigation was designed to
      further examine the well-being of family caregivers, explore the domains of
      worry, and assess to what extent "content-dependent" worry could be associated
      with the caregivers' health METHODS: The sample consisted of 100 family
      caregivers of oncological patients assisted at home. Participants completed a
      battery of self-report questionnaires (Penn State Worry Questionnaire, Worry
      Domain Questionnaire, Hospital Anxiety and Depression Scale, Family Strain
      Questionnaire Short Form, and Psychophysiological Questionnaire of the Battery
      CBA 2.0). RESULTS: The level of worry was medium-high among participants, and
      caregivers worry more about their occupation and future. Depression, anxiety, and
      somatic symptomatology levels resulted mild, while strain level resulted high.
      Statistical analyses confirm the conclusions of the previous study, revealing a
      significant positive correlation between worry levels and caregivers'
      psychophysical health. Innovatively, it has been highlighted that who has higher
      scores of content-dependent worry shows also higher levels of strain, somatic
      symptoms, anxiety, and depression CONCLUSIONS: Not only trait-worry ("content
      free" measure) but also content-dependent worry is associated with strain and
      negative health outcomes. People may worry about different targets, and it might
      be useful to further investigate what are the specific worriers of family
      caregivers in order to promote their physical and emotional well-being.

PMID- 26201752
TI  - Photocatalytic Formic Acid Conversion on CdS Nanocrystals with Controllable
      Selectivity for H2 or CO.
AB  - Formic acid is considered a promising energy carrier and hydrogen storage
      material for a carbon-neutral economy. We present an inexpensive system for the
      selective room-temperature photocatalytic conversion of formic acid into either
      hydrogen or carbon monoxide. Under visible-light irradiation (lambda>420 nm, 1
      sun), suspensions of ligand-capped cadmium sulfide nanocrystals in formic
      acid/sodium formate release up to 116+/-14 mmol H2 g(cat)(-1) h(-1) with >99%
      selectivity when combined with a cobalt co-catalyst; the quantum yield at
      lambda=460 nm was 21.2+/-2.7%. In the absence of capping ligands, suspensions of
      the same photocatalyst in aqueous sodium formate generate up to 102+/-13 mmol CO
      g(cat)(-1) h(-1) with >95% selectivity and 19.7+/-2.7% quantum yield. H2 and CO
      production was sustained for more than one week with turnover numbers greater
      than 6*10(5) and 3*10(6), respectively.

PMID- 26201753
TI  - Is It Time to Reconsider Offer Versus Serve?

PMID- 26201755
TI  - Self-Reported Frequency and Perceived Severity of Being Bullied Among Elementary
      School Students.
AB  - BACKGROUND: This study reports students' perspectives on the frequency and
      perceived severity of being bullied. METHODS: A sample of 1816 elementary school
      students completed self-report surveys of perceived severity and frequency of
      being bullied. A Rasch technique aligned different victimized behaviors on
      interval logit scales. A 4-fold schema was used to identify the intersection
      between the perceived severity and frequency of being bullied. RESULTS: There was
      not a statistically significant correlation between the 2 measures (r = .02).
      Behaviors that included being hit and kicked, being cursed at, being ostracized,
      being threatened, being shoved or tripped, having one's friendship ruined, and
      being spoken ill of in public were perceived as severe and frequent bullying
      experiences. While boys reported more frequent experiences of being bullied,
      girls perceived bullying to have greater severity. CONCLUSIONS: Self-reported
      frequency does not necessarily correspond to the perceived severity of school
      bullying, a finding with implications for prevention and intervention initiatives
      designed or carried out by researchers and school psychologists.

PMID- 26201754
TI  - Socioeconomic Differences in the Association Between Competitive Food Laws and
      the School Food Environment.
AB  - BACKGROUND: Schools of low socioeconomic status (SES) tend to sell fewer healthy
      competitive foods/beverages. This study examined whether state competitive food
      laws may reduce such disparities. METHODS: School administrators for fifth- and
      eighth grade reported foods and beverages sold in school. Index measures of the
      food/beverage environments were constructed from these data. Schools were
      classified into SES tertiles based on median household income of students' postal
      zip code. Regression models were used to estimate SES differences in (1) Healthy
      School Food Environment Index (HSFEI) score, Healthy School Beverage Environment
      Index (HSBEI) score, and specific food/beverage sales, and (2) associations
      between state competitive food/beverage laws and HSFEI score, HSBEI score, and
      specific food/beverage sales. RESULTS: Strong competitive food laws were
      positively associated with HSFEI in eighth grade, regardless of SES. Strong
      competitive beverage laws were positively associated with HSBEI particularly in
      low-SES schools in eighth grade. These associations were attributable to schools
      selling fewer unhealthy items, not providing healthy alternatives. High-SES
      schools sold more healthy items than low-SES schools regardless of state laws.
      CONCLUSIONS: Strong competitive food laws may reduce access to unhealthy
      foods/beverages in middle schools, but additional initiatives are needed to
      provide students with healthy options, particularly in low-SES areas.

PMID- 26201756
TI  - Attitudes and Beliefs of Nonspecialist and Specialist Trainee Health and Physical
      Education Teachers Toward Obese Children: Evidence for "Anti-Fat" Bias.
AB  - BACKGROUND: The aim of this study was to assess the beliefs and attitudes of
      preservice health and physical education (HPE) specialist and nonspecialist
      schoolteachers toward obese children. METHODS: A total of 177 nonspecialist and
      62 HPE specialist trainee teachers completed a series of pen-and-paper validated
      measures of attitudes and beliefs toward obese children. RESULTS: Both groups of
      preservice teachers reported strong implicit and moderate explicit anti-fat bias.
      Enrollment in the HPE specialist degree was found to be a significant predictor
      of both implicit bad/good anti-fat bias (beta = 3.97, p = .002) and implicit bias
      on the stupid/smart scale (beta = 2.983, p = .016) of the IAT. Beliefs that obese
      children were less healthy, more self-conscious, and less satisfied with
      themselves were strongly endorsed by the majority of participants. HPE
      specialists were found to have significantly lower expectations for obese
      children in regard to "reasoning" (mean difference = 0.21, p = .0107) and
      "cooperation" skills (mean difference = 0.25, p = .0354) compared to
      nonspecialist trainees. CONCLUSIONS: This study is the first to document the
      strong anti-fat bias of both preservice nonspecialist and HPE specialist
      teachers. It is also the first to find that preservice HPE specialist teachers
      have stronger anti-fat biases and differential expectations regarding particular
      abilities of obese children, compared to nonspecialists.

PMID- 26201757
TI  - Public Disclosure to Improve Physical Education in an Urban School District:
      Results From a 2-Year Quasi-Experimental Study.
AB  - BACKGROUND: Many elementary schools have policies requiring a minimum amount of
      physical education (PE). However, few schools comply with local/state PE policy
      and little is known about how to improve adherence. We evaluated changes in PE
      among fifth-grade classes, following participatory action research efforts to
      improve PE quantity and policy compliance that focused on publically disclosing
      PE data. METHODS: Data were collected in 20 San Francisco public elementary
      schools in spring 2011 and 2013. PE schedules were collected and PE classes were
      directly observed (2011, N = 30 teachers; 2013, N = 33 teachers). Data on the
      proportion of schools meeting state PE mandates in 2011 were shared within the
      school district and disclosed to the general public in 2012. RESULTS: From 2011
      to 2013, PE increased by 11 minutes/week based on teachers' schedules (95% CI:
      3.0, 19.6) and by 14 minutes/week (95% CI: 1.9, 26.0) based on observations. The
      proportion of schools meeting the state PE mandate increased from 20% to 30% (p =
      .27). CONCLUSIONS: Positive changes in PE were seen over a 2-year period
      following the public disclosure of data that highlighted poor PE policy
      compliance. Public disclosure could be a method for ensuring greater PE policy
      adherence.

PMID- 26201758
TI  - Trends in Cyberbullying and School Bullying Victimization in a Regional Census of
      High School Students, 2006-2012.
AB  - BACKGROUND: Schools are increasingly being called upon to address cyberbullying
      and its consequences. This study compares cyberbullying and school bullying
      trends and examines help-seeking among cyberbullying victims. METHODS: We
      analyzed self-report data over 4 surveys (2006-2012) from more than 16,000
      students in 17 MetroWest Boston high schools. Using generalized estimating
      equations, we examined school and cyberbullying victimization trends by sex,
      grade, and sexual orientation. RESULTS: From 2006 to 2012, cyberbullying
      increased from 15% to 21% (p < .001). In 2006, school bullying was 1.7 times
      higher than cyberbullying (26% versus 15%); by 2012, school bullying and
      cyberbullying were similar (23% versus 21%). Cyberbullying increased more among
      girls (17% to 27%; p < .001) than boys (12% to 15%; p < .001). There was no net
      increase in school bullying among girls (26% in 2006 and 2012) and a decrease
      among boys (25% to 18%; p < .001). Sexual minorities were more likely than
      heterosexuals to be bullied at school and online at every survey. Only 33% of
      cyberbullying victims told an adult; more victims told parents/non-school adults
      (29%) than school adults (17%). CONCLUSIONS: Despite decreases in school
      bullying, cyberbullying rose steadily, particularly among girls. Increased
      attention to sociodemographic differences in bullying could promote help-seeking
      and positive online behavior.

PMID- 26201759
TI  - School Experiences Associated With Alcohol Use Among Hispanic Youth.
AB  - BACKGROUND: The primary purpose of this study was to determine if recent alcohol
      use and binge drinking was associated with school experiences among Hispanic
      youth. METHODS: We performed a secondary analysis of the 2012 National Survey on
      Drug Use and Health (NSDUH). The NSDUH was administered to Hispanic youth (N =
      3457) in the privacy of their own homes. The school experience score was
      dichotomized into negative and positive school experiences. RESULTS: A total of
      13.8% of Hispanic youth reported recent alcohol use, and 8.0% reported that they
      had engaged in binge drinking. Hispanic youth who reported having negative school
      experiences were at increased odds for reporting recent alcohol use and binge
      drinking compared to counterparts with positive school experiences. Specifically,
      Hispanic students who were at highest risk for reporting recent alcohol use and
      binge drinking were in the age group 14 to 15 years, and the age group 16 to 17
      years who reported having negative school experiences. CONCLUSIONS: These
      findings on school experiences should be considered when developing and
      implementing school-based prevention programs targeting Hispanic youth.

PMID- 26201760
TI  - Developing a Policy to Address Nonsuicidal Self-Injury in Schools.
AB  - BACKGROUND: Nonsuicidal self-injury (NSSI) is an increasing and serious concern
      in schools. The purpose of this study was to determine the suitability of a new
      policy for responding to NSSI in schools. METHODS: Teachers and other school
      staff, including year level coordinators, psychologists, and counselors, N = 48,
      reviewed a policy for addressing NSSI in schools and provided written feedback.
      RESULTS: The majority of staff worked in schools without a policy regarding NSSI,
      or were unsure whether their school had such a policy. Participants were
      generally positive about the presented policy and supported its implementation in
      schools. Perceived challenges to policy implementation included a lack of
      knowledge about NSSI among staff and limited referral services available to
      students who self-injure. Suggested changes included developing a flowchart of
      the referral process and increasing collaboration between school staff, changes
      which were subsequently implemented. CONCLUSION: Awareness and education for
      school staff regarding NSSI combined with school policies for responding to
      adolescents who self-injure are recommended to enhance management of NSSI in
      schools, and improve the health and well-being of adolescents who self-injure.

PMID- 26201761
TI  - How Food as a Reward Is Detrimental to Children's Health, Learning, and Behavior.
AB  - BACKGROUND: Despite small- and wide-scale prevention efforts to curb obesity, the
      percentage of children classified as overweight and obese has remained relatively
      consistent in the last decade. As school personnel are increasingly pressured to
      enhance student performance, many educators use food as a reward to motivate and
      reinforce positive behavior and high achievement. Yet, many educators have missed
      the link between student health and academic achievement. METHODS: Based on a
      review of the literature, this article explores the link between childhood
      obesity and adverse mental and physical health, learning, and behavior outcomes.
      The role in providing children with food as a reward in the relationship between
      obesity and detrimental health and performance outcomes are examined. RESULTS:
      The use of food as a reward is pervasive in school classrooms. Although there is
      a paucity of research in this area, the few studies published in this area show
      detrimental outcomes for children in the areas of physical health, learning, and
      behavior. CONCLUSIONS: It is imperative that educators understand the adverse
      outcomes associated with using food as a reward for good behavior and
      achievement. This study provides alternatives to using food as a reward and
      outlines future directions for research.

PMID- 26201762
TI  - Experimental hyperlipidemia induces insulin resistance in sheep.
AB  - This study aimed to evaluate the effects of intravenous infusion of a soybean
      based lipid emulsion on some blood energy-related metabolites and insulin
      sensitivity indexes in sheep. Four clinically healthy ewes were assigned into a 2
      treatment, 2-period cross-over design. Either normal saline (NS) or lipid
      emulsion (LE) was intravenously introduced at a rate of 0.025 mL.kg(-1) min(-1)
      for 6 h. The concentrations of blood nonesterified fatty acid (NEFA), beta
      hydroxybutyrate, triglyceride, cholesterol, urea, creatinine, cortisol, glucose,
      and insulin were measured at different time points. After 6 h, intravenous
      glucose tolerance test was performed. Lipid infusion elicited an increase (P <
      0.05) in the NEFA, beta-hydroxybutyrate, and triglyceride concentrations compared
      with the baseline value and NS infusion. Infusion of NS did not influence blood
      glucose concentration; however, LE infusion increased plasma glucose
      concentration (P < 0.05). At time point 12 h, serum insulin concentrations were
      increased (P < 0.05) in NS treatment; however, such an increase was not observed
      in the LE treatment. Insulin sensitivity index for the LE infusion was lower (P <
      0.05) than that for the NS treatment. The glucose effectiveness was not (P >
      0.05) different among treatments. In the LE treatment, acute-phase insulin
      responses increased (P < 0.05) and disposition index decreased (P < 0.001)
      compared with NS treatment. The results showed that experimentally induced NEFA
      in blood could cause insulin resistance in sheep. The current model could be used
      to evaluate the pathogenesis of conditions associated with increased lipid
      mobilization and insulin resistance. 

PMID- 26201763
TI  - Duration of fasting but not diurnal variation affects the response to glucagon in
      healthy cats.
AB  - The role of glucagon disturbances in diabetes is increasingly recognized.
      Glucagon stimulation tests (GSTs) have been described in cats previously, but
      information is lacking on the response of cats to glucagon under specific
      conditions. The aim of this study was to assess a novel protocol for GST using
      human-recombinant glucagon and the effect of diurnal variation and duration of
      fasting using this protocol in healthy cats. All intravenous doses resulted in
      occasional vomiting and nausea, and eventually, a 20-MUg/kg intramuscular dose
      was chosen. Five healthy cats were then used in a repeated-measures study. Cats
      were free-fed regularly at 7:30 AM and 5:30 PM for 30 min. In each cat, GST was
      performed at 7 PM after a 25-h fast (PM25), at 9 AM after a 25-h fast (AM25), and
      at 9 AM after a 15-h fast (AM15). Glucose and insulin concentrations were
      measured at -15, 0, 15, 25, 35, 45, and 60 min after stimulation. Baseline and
      peak concentrations were compared using the Friedman test. Baseline glucose and
      insulin did not differ significantly between treatment groups. Peak glucose
      concentrations occurred at 15 min and were significantly higher (P = 0.0085) at
      AM15 (mean +/- standard deviation = 185.2 +/- 43.0 mg/dL) vs AM25 (144.4 +/- 10.5
      mg/dL) and PM25 (128.0 +/- 18.4 mg/dL). Similarly, peak insulin concentrations
      occurred at 15 min and were significantly higher (P = 0.04) at AM15 (1,911 +/-
      1,153 pg/mL) vs AM25 (739 +/- 52 pg/mL) or PM25 (549 +/- 366 pg/mL). In
      conclusion, prolonged fasting significantly blunted the glycemic response to
      glucagon compared with shorter fasting, but diurnal variation had no significant
      effect on glucose or insulin responses. 

PMID- 26201764
TI  - Could burning fat start with a brite spark? Pharmacological and nutritional ways
      to promote thermogenesis.
AB  - There are two types of adipose tissue with distinct functions-white adipose
      tissue stores chemical energy as triglycerides, whereas brown adipose tissue
      consumes energy and releases heat (thermogenesis) in response to sympathetic
      nerve activity. In humans, treatments that promote greater brown adipose tissue
      deposition and/or activity would be highly beneficial in regimes aimed at
      reducing obesity. Adult humans have restricted populations of prototypical brown
      adipocytes in the neck and chest areas, but recent advances have established that
      adipocytes with similar properties, termed "brite" adipocytes, can be recruited
      in subcutaneous depots thought to be primarily white adipose tissue. These brite
      adipocytes express the protein machinery required for thermogenesis, but to
      assess brite adipocytes as viable therapeutic targets we need to understand how
      to promote conversion of white adipocytes to brite adipocytes and ways to
      increase optimal energy consumption and thermogenesis in these brite adipocytes.
      This can be accomplished by pharmacological and nutritional therapies to
      differing degrees, as reviewed in detail here. 

PMID- 26201765
TI  - "Cancer Survivors" as Voluntary Helpers in Cancer Associations in France. Limits
      of the Balance between Service Offer and Social Demand.
AB  - Historically, in France, cancer associations have been managed by doctors.
      Despite this, the French healthcare system has increasingly encouraged them to
      attract voluntary helpers who are not health workers. This development has given
      rise to the question of the competence and legitimacy of voluntary workers in
      cancer associations. The aim of the present study was to identify the skills
      possessed by voluntary helpers who have survived the disease and the extent to
      which their skills meet the needs of cancer associations in responding to the
      demands that have emerged in this new context. This is a qualitative study based
      on data collected during semi-directed interviews, focus group sessions and on
      site observations in a variety of French cancer associations. Categorical and
      thematic analyses were then carried out separately for each ethnographic method
      used. The study showed that because the commitment of survivor voluntary helpers
      derives from their own experience of the disease, it is inconsistent with the
      fulfilment of the association's collective aims, such as the search for funding
      or project development. These helpers nevertheless play an important role that
      involves a special link between the individual and the group, between the
      community and society. To conclude, "involved" volunteers have to reconcile their
      individual expectations with the association's collective aims.

PMID- 26201766
TI  - MELD-good for many, not as good for others ... at least for now.

PMID- 26201767
TI  - The BAFFling problem of B cell-activating factor in nonalcoholic fatty liver
      disease.

PMID- 26201768
TI  - Autoimmune acute liver failure: an emerging etiology for intractable acute liver
      failure.
AB  - Diagnosis of acute onset autoimmune hepatitis (AIH) is the most challenging task
      because of atypical clinicopathological features. We examined the nature of acute
      onset AIH consisting of nonsevere, severe, and fulminant AIH based on our
      published data and other published papers, and propose how to diagnose and treat
      this intractable hepatitis. We analyzed clinical, biochemical, immunological,
      radiological, and histological features of acute onset AIH. Thirty percent of
      fulminant hepatitis was due to AIH and autoimmune acute liver failure (ALF) was
      not rare. The important characteristic of acute onset AIH is its histological,
      radiological, and clinical heterogeneity. Sometimes acute onset AIH develops into
      ALF in a sub-acute clinical course without appropriate diagnosis and treatment,
      and becomes resistant to immunosuppressive therapy and has poor prognosis.
      Unenhanced computed tomography (CT) often shows heterogeneous hypoattenuation in
      autoimmune ALF. The revised original scoring system (1999) performed better in
      patients with acute onset AIH than the simplified scoring system (2008). Liver
      regeneration from periportal progenitor cells to mature hepatocytes was impaired
      in ALF, resulting in resistance to immunosuppressive therapy. Precise
      histological evaluation (the presence of centrilobular necrosis/collapse) along
      with the revised original scoring system and CT findings of heterogeneous
      hypoattenuation after systematic exclusion of other causes 36 plays an important
      role in the diagnosis. The most important strategy for autoimmune ALF is to
      diagnose and treat acute onset AIH before its development into ALF. Liver
      transplantation should be considered before the occurrence of infectious
      complications in the case of fulminant liver failure. 

PMID- 26201769
TI  - Model for End-Stage Liver Disease and liver cirrhosis-related complications.
AB  - The Model for End-Stage Liver Disease (MELD) score has gained wide acceptance for
      predicting survival in patients undergoing liver transplantation. The strength of
      this score remains in the mathematical formula derived from a multivariate Cox
      regression analysis; it is a continuous scale and lacks a ceiling or a floor
      effect with a wide range of discrimination. It is based on objective,
      reproducible, and readily available laboratory data and the wide range of samples
      which have been validated. Liver cirrhosis complications such as ascites,
      encephalopathy, spontaneous bacterial peritonitis and variceal bleeding were not
      considered in the MELD score underestimating their direct association with the
      severity of liver disease. In this regard, several recent studies have shown that
      clinical manifestations secondary to portal hypertension are good prognostic
      markers in cirrhotic patients and may add additional useful prognostic
      information to the current MELD. We review the feasibility of MELD score as a
      prognostic predictor in patients with liver cirrhosis-related complications. 

PMID- 26201770
TI  - Non-invasive assessment of liver fibrosis in patients with chronic hepatitis B.
AB  - In patients with chronic hepatitis B (CHB), liver fibrosis assessment is
      essential not only for determining prognosis but also for identifying patients
      who should receive treatment. Liver biopsy is limited by its invasiveness and
      sampling error. To explore effective non-invasive methods for liver fibrosis
      assessment, we reviewed international literature published over the past decade
      that focused on patients with CHB. Biomarker panels such as API, FIB-4, Forns
      Index, HepaScore, FibroMeter, FibroTest, Zeng Index and Hui Index detect advanced
      fibrosis and cirrhosis with fairly satisfactory accuracy with area under the
      receiver-operating characteristics curve higher than 0.85. However, most panels
      and the suggested cutoffs have not been independently validated. Transient
      elastography is accurate in detecting advanced fibrosis and cirrhosis, and the
      relative cutoffs have been defined. False-positive results may, however, occur in
      cases of active necroinflammation and cholestasis. Other promising imaging
      methods such as acoustic radiation force impulse and magnetic resonance
      elastography still require further validating studies. We conclude that transient
      elastography, FibroTest and API are the most widely validated. Transient
      elastography has been validated as the most useful non-invasive method for liver
      fibrosis assessment. To improve non-invasive performance of detecting liver
      fibrosis, a combined application of transient elastography and biomarkers may be
      the preferred course of action. 

PMID- 26201771
TI  - Role of anticoagulant therapy in liver disease.
AB  - Anticoagulant therapy is a cornerstone in the treatment of different liver
      diseases. In Budd-Chiari syndrome (BCS), survival rates have increased
      considerably since the introduction of a treatment strategy in which
      anticoagulation is the treatment of first choice. In all patients diagnosed with
      acute portal vein thrombosis (PVT), anticoagulant therapy for at least 3 months
      is indicated. Anticoagulation should also be considered in patients with chronic
      PVT and a concurrent prothrombotic risk factor. Current evidence suggests that
      patients with PVT in cirrhosis will benefit from treatment with anticoagulation
      as well. In severe chronic liver disease the levels of both pro- and
      anticoagulant factors are decreased, resetting the coagulant balance in an
      individual patient and making it more prone to deviate to a hypo- or
      hypercoagulable state. An increased activity of the coagulation cascade is not
      solely a feature of chronic liver disease; it influences the development of liver
      fibrosis as well. Several studies in animals and humans have shown that
      anticoagulation could prevent or improve fibrogenesis and even disease
      progression in cirrhosis. Anticoagulation is therefore a promising antifibrotic
      treatment modality. 

PMID- 26201772
TI  - The risk factors and diagnosis of cholangiocarcinoma.
AB  - Cholangiocarcinoma (CC) is a generally fatal malignancy of the biliary tree. Its
      incidence is increasing worldwide. Unfortunately, the diagnosis of CC frequently
      occurs late in the course of the disease, which contributes to the high mortality
      rate. Securing the diagnosis can prove difficult and may require a combination of
      imaging modalities, serum markers, and tissue sampling. Even with current best
      practice accurate diagnosis and staging is often elusive. We review current
      trends in the epidemiology of CC, current best practice in its diagnosis, and
      some of the emerging technologies and systems that may lead to improved
      diagnosis, staging, and, perhaps, outcome. 

PMID- 26201773
TI  - The HepaRG cell line: a valuable in vitro tool for hepatitis virus infection
      studies.
AB  - Hepatitis virus infections, mainly hepatitis B virus (HBV) and hepatitis C virus
      (HCV) infections, constitute a major problem for public health since they have a
      worldwide distribution and because they are associated with hepatocellular
      carcinoma and death. Current anti-HBV vaccines seem to be effective in the
      majority of people. However, an important issue waiting to be tackled nowadays is
      how to cure patients with chronic hepatitis B. Moreover, no vaccine is available
      today for the prevention of HCV infection. Therefore, the use of adequate in
      vitro infection systems is a prerequisite for the molecular understanding of the
      infection events of these viruses, which could result in the development of novel
      powerful therapeutics. In this respect, the HepaRG cell line exhibits a
      hepatocyte-like morphology and displays drug metabolism capacity similar to that
      of primary hepatocytes. HepaRG cells have yet been proven to be a useful tool in
      the study of viral infections, particularly for deciphering the mechanism of HBV
      entry into hepatocytes. 

PMID- 26201774
TI  - Nonalcoholic fatty liver disease following liver transplantation.
AB  - Post-transplant, nonalcoholic hepatic steatosis and steatohepatitis are
      increasingly recognized as a complication of liver transplantation, and the
      progression of the latter through fibrosis to cirrhosis has been clearly shown.
      Non-alcoholic steatohepatitis (NASH) is independently associated with an
      increased risk of death from cardiovascular and liver diseases. While optimal
      therapy is not yet available in the post-liver transplant setting, knowledge
      gained in the therapy of NASH in the non-transplant setting can be used to design
      therapeutic interventions. In addition, early recognition with protocol liver
      biopsies and an effective preventive strategy by modifying known risk factors
      implicated in the recurrence of NASH would be the most effective way to curtail
      the progression of NASH before an effective treatment can be found. Additional
      rigorous research aimed at elucidating the pathogenesis, natural history, and
      selection of immunosuppressants for NASH is clearly warranted. 

PMID- 26201776
TI  - Hepatitis B virus genotype C encoding resistance mutations that emerge during
      adefovir dipivoxil therapy: in vitro replication phenotype.
AB  - INTRODUCTION: Hepatitis B virus (HBV) can be classified into ten genotypes (A-J),
      with genotypes B and C being the most common in Asia. Recent data suggest that
      the HBV genotype can influence disease progression, and genotype C has been
      associated with more aggressive liver disease than that of other genotypes.
      Although there is a preventative vaccine, chronic infection remains a public
      health problem with oral nucleos(t)ide analog therapy being the most common
      treatment. The HBV genome is composed of four partially overlapping reading
      frames, meaning that substitutions in the HBV polymerase selected during NA
      therapy may also alter the overlapping HBV surface antigen (HBsAg). We have
      recently shown that for HBV genotype D, the rtA181T/sW172stop substitution
      conferring resistance to adefovir dipivoxil (ADV) alters secretion of HBsAg and
      exerts a dominant-negative effect on wild-type virion secretion. However, the
      effect of this and other ADV-resistance-associated mutations on HBV replication
      and HBsAg secretion for the HBV genotype C, the genotype with the most severe
      clinical prognosis, is unknown. METHODS/RESULTS: We constructed 1.2-mer
      infectious cDNA clones of HBV genotype C encoding mutations associated with ADV
      resistance and established an in vitro replication assay in Huh7 cells. Decreased
      levels of HBV DNA and HBsAg were detected for all ADV variants relative to the
      1.2-mer wild-type polymerase control plasmid. Importantly, less HBsAg was
      detected in the cells transfected with the rtA181T resistance mutants, and the
      overlapping sW172stop mutation ablated secretion of HBsAg into cell culture
      supernatants. CONCLUSIONS: The identification of secretion-defective HBV in the
      setting of ADV therapy for HBV genotype C, and to a lesser extent HBV genotype B,
      has major implications for the diagnosis and treatment of HBV in the Asia-Pacific
      region, as it is likely that quantitative HBsAg and viral load testing of serum
      from patients infected with HBV encoding rtA181T and rtN236T substitutions may
      not accurately reflect the level of replication within hepatocytes.

PMID- 26201777
TI  - Are physicians following guidelines? A survey of Hepatitis B management
      strategies.
AB  - PURPOSE: Practice guidelines for chronic hepatitis B (CHB) assist physicians in
      management; however, there are also areas where they provide no guidance. This
      paper aimed to examine treatment preferences for CHB among physicians based upon
      the Asia Pacific Association for the Study of the Liver (APASL) consensus
      guidelines 2008. METHODS: A questionnaire was prepared consisting of 18 questions
      grouped into 8 sections: basic information of participants, the proportion and
      number of CHB patients on treatment, case scenarios of treatment initiation,
      preferences for antiviral therapy, scenarios for stopping and continuing
      antiviral therapy, monitoring patients during therapy, and viral resistance
      management. The questionnaire was introduced to the APASL 2009 conference
      delegates. RESULTS: A total of 508 participants from 34 countries participated in
      the survey. Lamivudine or peg-interferon monotherapy was the preferred first-line
      therapy, while lamivudine/adefovir combination was the drug of choice for rescue
      therapy. Drug efficacy and cost were the most important factors to consider
      before initiating treatment, while viral resistance had a low priority. In
      general, the APASL guideline was strictly followed in about 50-60 % of the
      scenarios (initiating, stopping, or continuing antiviral therapy). CONCLUSIONS:
      The survey concluded that clinical management preferences differed from APASL
      guidelines in many instances.

PMID- 26201778
TI  - Entecavir improves the outcome of acute-on-chronic liver failure due to the acute
      exacerbation of chronic hepatitis B.
AB  - BACKGROUND: The mortality of acute-on-chronic hepatitis B liver failure (ACHBLF)
      from acute exacerbation of chronic hepatitis B is 30-70 % without liver
      transplant. METHODS: We conducted an open-label, prospective, 48-week study to
      evaluate the efficacy of entecavir (ETV) in ACHBLF with 110 patients who received
      either ETV or no treatment. Primary measurements were survival and improvement in
      disease severity scores. RESULTS: Of the 110 patients enrolled, 2 withdrew
      consent, 108 were treated with 53 ETV, and 55 were untreated. When compared to
      the patients in the untreated group at week 48, a lower cumulative mortality rate
      in ETV-treated patients was observed [54.7 % (29/53) vs. 78.2 % (43/55), p <
      0.01). ETV treatment significantly improved disease severity scores including
      Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), and MELD
      sodium (MELD-Na). All ETV-treated subjects achieved an undetectable HBV DNA level
      (<500 copies/mL; 100 % vs. 7.9 %, p < 0.001). In univariate analysis, predictors
      of survival at week 48 included baseline age, total bilirubin, international
      normalized ratio of prothrombin time, albumin, cholesterol, receiving ETV
      therapy, CTP, MELD, MELD-Na, and sequential organ failure assessment (SOFA)
      scores. In multivariate analysis, baseline age, total bilirubin, untreated (with
      ETV), CTP, and SOFA scores were the independent risk factors for mortality.
      CONCLUSIONS: Entecavir treatment for patients with ACHBLF significantly improves
      disease severity scores with a marked reduction in mortality and suppression in
      HBV DNA to undetectable levels at week 48. Patients' age, total bilirubin, CTP,
      and SOFA scores at baseline are independent risk factors for higher mortality
      without liver transplantation.

PMID- 26201775
TI  - Should visceral fat, strictly linked to hepatic steatosis, be depleted to improve
      survival?
AB  - Numerous epidemiologic studies have implicated abdominal obesity as a major risk
      factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease,
      stroke, metabolic syndrome and its further expression, i.e., nonalcoholic fatty
      liver disease and death. Using novel models of visceral obesity, several studies
      have demonstrated that the relationship between visceral fat and longevity is
      causal, while the accrual of subcutaneous fat does not appear to play an
      important role in the etiology of disease risk. The need of reducing the visceral
      fat to improve survival, mainly taking into account the strict link between
      nonalcoholic fatty liver disease and the coronary artery disease is discussed. 

PMID- 26201779
TI  - Clinicopathologic study on complications of orthotopic liver transplantation in
      54 patients with chronic hepatitis B viral infection.
AB  - OBJECTIVE: To study the complication incidence of 54 patients with chronic HBV
      infection following orthotopic liver transplantation (OLT) and risk factors
      associated with HBV recurrence and hepatocellular carcinoma (HCC) recurrence or
      metastasis post-OLT. METHODS: The light-microscopic appearance of hepatic
      allograft biopsies in 54 patients with chronic HBV infection following OLT was
      examined. The related clinical data were analyzed. The incidence and occurrence
      time of post-OLT complications were studied. Furthermore, the relationship
      between hepatitis B virus recurrence and acute rejection and the relationship
      among HCC recurrence/metastasis, acute rejection, tumor diameter, and portal vein
      invasion were particularly studied. RESULTS: Frequent complications of patients
      with chronic HBV infection following OLT were acute rejection [38 (70.4 %);
      occurrence time: 5-365 days], chronic rejection [1 (1.9 %); occurrence time: 10.7
      months], bile duct complications [24 (44.4 %);occurrence time: 7-940 days], HBV
      recurrence [7 (13.0 %); occurrence time: 1-540 days], HCV infection [3 (5.6 %);
      occurrence time: 60 days, 60 days, 33 months], CMV infection [8 (14.8 %);
      occurrence time: 67-90 days], and HCC recurrence or metastasis [17 (31.5 %);
      occurrence time: 2-41 months]. At the end of 1 year post-OLT, 95 % of patients
      with post-hepatitis B cirrhosis were alive. At the end of 3 years post-OLT, 85 %
      of patients with post-hepatitis B cirrhosis were alive. However, at the end of 1
      year post-OLT, 67.6 % of patients with post-hepatitis B HCC were alive. At the
      end of 3 years post-OLT, 50 % of patients with post-hepatitis B HCC were alive.
      The number of acute rejection episodes in patients with recurrent HBV infection
      and in those without recurrent HBV infection was 0.86 +/- 1.46 times/patient and
      1.07 +/- 0.90 times/patient, respectively (p > 0.05); the number of moderate
      acute rejection episodes (RAI score >=4) in patients with recurrent HBV infection
      and in those without recurrent HBV infection was 0.29 +/- 0.49 times/patient and
      0.50 +/- 0.63 times/patient (p > 0.05). Incidence of patients with >=3 episodes
      of acute rejection in patient with recurrent HBV infection and in those without
      recurrent HBV infection was 14.3 and 10.6 % (p > 0.05). Furthermore, the number
      of acute rejection episodes in patients with HCC recurrence or metastasis and in
      those without HCC recurrence or metastasis was 1.12 +/- 0.93 times/patient and
      1.06 +/- 1.39 times/patient, respectively (p > 0.05). The number of moderate
      acute rejection episodes (RAI score >=4) in patients with HCC recurrence or
      metastasis and in those without HCC recurrence or metastasis was 0.65 +/- 0.79
      times/patient and 0.65 +/- 1.06 times/patient, respectively (p > 0.05). Incidence
      of patients with >=3 episodes of acute rejection in patients with HCC recurrence
      or metastasis and in those without HCC recurrence or metastasis was 5.9 and 17.6
      %, respectively (p > 0.05). The tumor diameter in patients with HCC recurrence or
      metastasis was 6.72 +/- 3.40 cm; however, that in patients without HCC recurrence
      or metastasis was 3.55 +/- 2.17 cm (p = 0.0047). The incidence of portal vein
      invasion in patients with HCC recurrence or metastasis and in those without HCC
      recurrence or metastasis was 68.75 and 33.3 %, respectively (p = 0.006).
      CONCLUSION: There was no significant difference between HBV recurrence and acute
      rejection post-liver transplantation in patients with chronic HBV infection.
      There was no significant difference between HCC recurrence and acute rejection.
      The tumor diameter in patients with HCC recurrence or metastasis was
      significantly greater than that in patients with no HCC recurrence or metastasis.
      Portal vein invasion was significantly more frequent in patients with HCC
      recurrence or metastasis than in those with no HCC recurrence or metastasis.

PMID- 26201780
TI  - Combination and evolution of HBV mutant strains in the HBeAg-positive status
      predict clinical outcomes after HBeAg seroconversion.
AB  - PURPOSE: We investigated whether the combined presence and evolution of hepatitis
      B virus (HBV) mutant strains in the hepatitis B e antigen (HBeAg)-positive status
      can predict clinical outcomes after HBeAg seroconversion. METHODS: One hundred
      and eighty-six patients with spontaneous HBeAg seroconversion were enrolled into
      this longitudinal study. The sequences of pre-S, core promoter, and precore
      regions were determined at study entry and at the visit immediately before HBeAg
      seroconversion. RESULTS: Age >=40 years at HBeAg seroconversion, male sex, and
      higher HBV DNA levels at entry were independent predictors for HBeAg-negative
      chronic hepatitis B (CHB). Patients with combined mutations of pre-S deletions
      and T1762/A1764 had a significantly increased risk of cirrhosis and
      hepatocellular carcinoma (HCC) compared to patients with the wild type at both
      genomic regions. Combinations of pre-S deletions and T1762/A1764 were found on
      the same HBV genome by cloning analysis of full-length HBV genomes. Patients with
      a persistent presence of pre-S deletions and T1762/A1764 mutations, and new
      development of pre-S deletions in the HBeAg-positive status were significantly at
      an increased risk of HBeAg-negative CHB, cirrhosis, and HCC after HBeAg
      seroconversion than those with a persistent presence of the wild type at both
      genomic regions. After adjusting the other risk factors, the evolution of pre-S
      deletions was an independent predictor for cirrhosis [hazard ratio (HR): 1.52, 95
      % confidence interval (CI) 1.02-2.25] and HCC (HR: 4.0, 95 % CI 1.6-10.1).
      CONCLUSIONS: The combined presence and evolution of pre-S deletions and
      T1762/A1764 in the HBeAg-positive status was a useful factor significantly
      predictive of clinical outcomes in patients with spontaneous HBeAg
      seroconversion.

PMID- 26201781
TI  - Combining the HBsAg decline and HBV DNA levels predicts clinical outcomes in
      patients with spontaneous HBeAg seroconversion.
AB  - PURPOSE: The aim was to investigate whether the quantitation of the hepatitis B
      surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels can predict HBV
      reactivation and advanced liver disease after spontaneous hepatitis B e antigen
      (HBeAg) seroconversion. METHODS: A total of 121 patients who experienced
      spontaneous HBeAg seroconversion were included in this longitudinal study. Serial
      HBsAg and HBV DNA levels were measured before and after HBeAg seroconversion.
      RESULTS: Of the 121 patients, 32 experienced HBV reactivation and six achieved an
      HBsAg loss after HBeAg seroconversion during the follow-up period. The decline in
      the HBsAg level was considerably more pronounced in patients without HBV
      reactivation when compared to those with HBV reactivation (p = 0.016).
      Multivariate analysis revealed that the age of >40 years at HBeAg seroconversion,
      male sex, and HBsAg decline, and HBV DNA levels at month 12 after HBeAg
      seroconversion were independent factors for the development of HBeAg-negative
      hepatitis. All the six patients who achieved HBsAg loss had HBsAg level of <1,000
      IU/mL at month 12 after HBeAg seroconversion (p < 0.001). The risk of HBeAg
      negative hepatitis, cirrhosis, and HCC was substantially increased in patients
      who had a combination of both, i.e., no decline in the HBsAg level and HBV DNA
      level of >10(4) copies/mL at month 12 after HBeAg seroconversion. CONCLUSIONS:
      Combining HBsAg reduction and HBV DNA levels at month 12 after HBeAg
      seroconversion was a useful marker to predict clinical outcomes in spontaneous
      HBeAg seroconverters. HBsAg level of <1,000 IU/mL at month 12 after HBeAg
      seroconversion could predict the HBsAg loss after HBeAg seroconversion.

PMID- 26201782
TI  - Population-attributable estimates for risk factors associated with hepatitis B
      and C: policy implications for Pakistan and other South Asian countries.
AB  - INTRODUCTION: Reuse of contaminated syringes, high frequency of injections,
      tattooing and skin piercing have repeatedly been shown to be important and
      independent risk factors for the transmission of hepatitis B (HBV) and C (HCV)
      infections in South Asian countries. Estimation of population-attributable risks
      indicates the potential for hepatitis prevention if the exposure to certain
      modifiable factors can be eliminated. METHODS: We estimated the population
      attributable risks of various risk factors for transmission of HBV and HCV using
      data from a large, nationally representative survey conducted in 2007 across
      Pakistan, a country known to have a high prevalence of chronic viral hepatitis.
      Odds ratio estimates and observed prevalence of the risk factors were used for
      calculating PAR estimates. We also performed a systematic review of published
      studies that identify the prevalence of similar modifiable risk factors for HBV
      and HCV from other South Asian countries in order to define an overall prevention
      strategy for the region. RESULTS: For HBV, a high frequency (>10) of therapeutic
      injections in the past 1 year had an attributable risk of 3.5 % (95 % CI 2.9
      3.9), reuse of syringes had a 2.7 % risk (95 % CI 2.2-3.1), the practice of being
      shaved by a barber 2.1 % (95 % CI 1.7-2.6), sharing of smoking utensils 4.4 % (95
      % CI 3.8-4.9) and ear/nose piercing 1.4 % (95 % CI 1.2-1.7). Population
      attributable risks for HCV were as follows: high frequency of therapeutic
      injections in the past 1 year 11.3 % (95 % CI 10.5-11.7), reuse of syringes 6.2 %
      (95 % CI 6.1-6.9), practice of being shaved by a barber shop 7.9 % (95 % CI 7.1
      8.2), sharing of smoking utensils 8.1 % (95 % CI 6.9-8.5), practice of ear/nose
      piercing among females 5.9 % (95 % CI 5.2-6.1) and tattooing 5 % (95 % CI 4.3
      5.6). A systematic review showed that other South Asian countries share a number
      of common risk factors for the transmission of viral hepatitis. CONCLUSION: A
      substantial number of HBV and HCV infections in Pakistan and other South Asian
      countries can be prevented by key interventions targeted toward a few selected
      and modifiable risk factors. Hence, policies specifically targeted at key risk
      factors for HBV and HCV such as safe and rational use of injections prescribed by
      trained health-care providers are urgently needed for countries like Pakistan.

PMID- 26201783
TI  - Oxidative stress is closely associated with insulin resistance in genotypes 1 and
      3 chronic hepatitis C.
AB  - BACKGROUND: Chronic hepatitis C (CHC) infection is associated with insulin
      resistance and with oxidative stress, but the relationship between the two has
      not been thoroughly examined. PURPOSE: To evaluate the association between
      insulin resistance and oxidative stress in CHC patients. METHOD: In 115 CHC
      patients (68 with genotype 1 and 47 with genotype 3), the relationship between
      the serum concentration of malondialdehyde (MDA), a marker of oxidative stress
      and insulin resistance as defined by the homeostasis model (HOMA-IR) was
      examined. RESULTS: There was no significant difference in MDA levels between
      genotype 1- and genotype 3-infected subjects (12.882 vs. 12.426 ng/mL, p = 0.2).
      By univariate analysis, factors associated with HOMA-IR in both genotypes were
      oxidative stress as measured by MDA (p = 0.002), body mass index (BMI), portal
      activity, and fibrosis. Genotype-specific differences in HOMA-IR association were
      steatosis and triglycerides (TG) for genotype 1, and age and glutathione (GSH)
      for genotype 3. In a stepwise multiple linear regression analysis in both
      genotypes, MDA was a significant and independent predictor of HOMA-IR (p = 0.04).
      As expected, BMI and fibrosis were likewise independently correlated to HOMA-IR.
      In addition, MDA levels were higher (p < 0.001) and GSH levels were lower (p =
      0.023) in insulin-resistant subjects compared to their insulin-sensitive
      counterparts. CONCLUSIONS: It is concluded that in CHC, oxidative stress is an
      independent predictor of HOMA-IR, irrespective of virus genotype. Further studies
      on the role of oxidative stress in the development of insulin resistance in CHC
      are warranted.

PMID- 26201784
TI  - Inhibition of silent information regulator 1 induces glucose metabolism disorders
      of hepatocytes and enhances hepatitis C virus replication.
AB  - BACKGROUND AND OBJECTIVE: Glucose metabolism disorders including insulin
      resistance (IR) and type 2 diabetes are frequent and important cofactors of
      chronic hepatitis C (CHC). Silent information regulator 1 (SIRT1) plays a key
      role in the regulation of hepatic glucose metabolism. We investigated the
      possible effect of HCV replication on glucose metabolism of hepatocytes and
      expression of SIRT1 using Huh-7.5 cells harboring the HCV replicon. METHODS: The
      level of reactive oxygen species (ROS) and value of NAD(+)/NADH and ATP/ADP were
      detected. Glucose uptake by hepatocytes and glucose production were measured. The
      activity and expression levels of SIRT1 and expression of its downstream glucose
      metabolism genes were measured. RESULTS: In replicon cells, the level of ROS
      increased and the value of nicotinamide adenine dinucleotide (NAD(+))/NADH
      decreased, then the activity and expression level of mRNA and protein of SIRT1
      decreased. Inhibition of SIRT1 not only increased insulin receptor substrate-1
      phosphorylation and decreased Akt phosphorylation, inhibited cell surface
      expression of glucose transporter 2 and suppressed cellular glucose uptake, but
      it also decreased phosphorylation of forkhead box O1, then upregulated
      phosphoenolpyruvate carboxykinase and glucose 6-phosphatase genes and
      downregulated the glucokinase gene, thus promoting glucose production. Interferon
      treatment restored the aforementioned changes. SIRT1 activator improved glucose
      metabolism disorders by an increase in glucose uptake and a decrease in glucose
      production, and it inhibited HCV replication. CONCLUSIONS: HCV replication
      decreasing the NAD(+)/NADH ratio may downregulate the activity and expression of
      SIRT1, then change the expression profile of glucose metabolism-related genes,
      thereby causing glucose metabolism disorders of hepatocytes and promoting HCV
      replication. Treatment with SIRT1 activator improves glucose metabolic disorders
      and inhibits HCV replication, suggesting that restoration of SIRT1 activity may
      be a promising new therapeutic approach for CHC patients with IR.

PMID- 26201785
TI  - B cell-activating factor is associated with the histological severity of
      nonalcoholic fatty liver disease.
AB  - PURPOSE: B cell-activating factor (BAFF) is expressed in adipocytes and affects
      lipogenesis and insulin sensitivity. In addition, the BAFF receptor is expressed
      in visceral adipose tissue and liver. The aim of this study was to analyze serum
      BAFF levels in patients with nonalcoholic steatohepatitis (NASH) and simple
      steatosis (SS) and to compare their respective clinical and histological
      findings. METHODS: A total of 96 patients with nonalcoholic fatty liver disease
      (20 with SS and 76 with NASH) were enrolled and their serum BAFF levels were
      analyzed. Comprehensive blood chemistry analysis and histological examination of
      liver samples were also conducted. RESULTS: Serum BAFF levels were higher in
      patients with NASH than in those with SS (p = 0.016). NASH patients with
      ballooning hepatocytes and advanced fibrosis had higher levels of BAFF in sera (p
      = 0.016 and p = 0.006, respectively). In addition, the prevalence of NASH
      increased significantly as the serum BAFF level increased (p = 0.004). Higher
      serum BAFF levels were found to be an independent risk factor for development of
      NASH (OR 1.003, 95% CI 1.0003-1.006; p = 0.047). CONCLUSIONS: Nonalcoholic
      steatohepatitis patients had higher levels of serum BAFF than patients with SS,
      and higher levels were associated with the presence of hepatocyte ballooning and
      advanced fibrosis. The serum BAFF level may be a useful tool for distinguishing
      NASH from SS.

PMID- 26201786
TI  - Prevalence and risk factors of non-alcoholic fatty liver disease in a multiracial
      suburban Asian population in Malaysia.
AB  - BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in the
      Malaysian population is not known. Malaysia has a multiracial Asian population
      with three major Asian races: Malay, Chinese, and Indian living together. The aim
      of the study is to determine the prevalence and risk factors in a suburban
      Malaysian population. METHODS: Consecutive subjects who came for a health checkup
      at a suburban medical facility were recruited for the study. All individuals had
      clinical assessments, anthropometric measurements, blood tests, and
      ultrasonography of the liver performed. Those with significant alcohol
      consumption and history of chronic liver disease were excluded. RESULTS: Of the
      1,621 "health screened" individuals analyzed, 368 (22.7 %) were found to have
      NAFLD. They comprised Chinese 1,269 (78.3 %), Malay 197 (12.1 %), and Indian 155
      (9.6 %). Males and "older" age group >=45 years had high prevalence rates with
      the highest in Indian (68.2 %) and Malay (64.7 %) males. Chinese females <45
      years had the lowest prevalence of 5.2 %. A significant increase in the
      prevalence of fatty liver between age <45 years and >=45 years was seen in female
      of all three races but in male, this increase was seen only among the Indians.
      NAFLD was strongly associated with diabetes mellitus, glucose intolerance, body
      mass index >=23, low high-density lipoprotein cholesterol, hypertriglyceridemia,
      and hypertension. CONCLUSION: NAFLD is common in suburban Malaysian population.
      Older Indian and Malay males have an inordinately high prevalence of the disease.

PMID- 26201787
TI  - High alanine aminotransferase level as a predictor for the incidence of
      macrovascular disease in type 2 diabetic patients with fatty liver disease.
AB  - PURPOSE: We investigated whether fatty liver (FL) disease in type 2 diabetic
      mellitus (T2DM) patients affects their incidence of macrovascular disease. In
      addition, we detected a useful marker for predicting the incidence of
      macrovascular disease events. METHODS: A total of 458 patients who underwent
      abdominal ultrasonography (US) between April 2003 and March 2004 in a diabetic
      clinic were divided into FL (n = 211) and non-FL (NFL; n = 247) groups, and
      followed by a diabetologist and/or hepatologist for 5 years. RESULTS: No
      significant difference in the incidence of macrovascular disease, neither
      cerebrovascular disease nor coronary heart disease, was observed between FL and
      NFL patients. Interestingly, in FL diabetic patients, only an alanine
      aminotransferase (ALT) level >=30 IU/l was significantly associated with the
      incidence of macrovascular events in univariate (odds ratio [OR], 10.632; 95 %
      confidence interval [CI], 1.302-86.841; p = 0.0274) and multivariate (OR, 10.134;
      CI 1.223-83.995; p = 0.0318) analyses. Patients with higher ALT levels had a
      higher cumulative incidence of macrovascular disease events than did those with
      lower ALT levels (p = 0.0068). In conclusion, an ALT level >=30 IU/l is an
      independent risk indicator of macrovascular disease in diabetic patients with
      FLD, whereas the presence of FL itself in T2DM patients is not associated with an
      increased incidence of macrovascular events. CONCLUSIONS: Our findings indicate
      that therapeutic interventions may be necessary for FL patients with high ALT
      levels to prevent macrovascular disease.

PMID- 26201788
TI  - Maturation defective myeloid dendritic cells in nonalcoholic fatty liver disease
      patients release inflammatory cytokines in response to endotoxin.
AB  - PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is characterized by the
      presence of elevated circulating endotoxin levels. The continuous presence of
      endotoxin might be responsible for inducing activation of the innate immune
      system resulting in chronic sub-clinical inflammation. This study examines the
      status of dendritic cells (DCs), an important component of innate immune system,
      in patients with NAFLD. METHODS: Effect of lipopolysaccharide (LPS) stimulation
      on maturation and activation of monocyte derived dendritic cells (mo-DCs) was
      evaluated in ten patients with NAFLD using flow cytometry, endocytosis assay,
      cytokine assay and mixed leukocyte reaction. RESULTS: Although the frequency of
      mo-DCs in NAFLD patients was similar to that of healthy controls, there was no
      upregulation in levels of HLA-DR, CD83, CD80 and CD86 on their surface in
      response to LPS stimulation ex vivo. Although the mo-DC from patients had higher
      endocytosing and lower allostimulatory capacities as compared to healthy controls
      indicating maturation defects yet they secreted significantly high amount of TNF
      alpha and IL-6 suggesting higher activation state. CONCLUSIONS: Our results
      indicate that DCs in patients with NAFLD exhibit immature yet functionally
      activated phenotype in response to LPS stimulation as they secrete inflammatory
      cytokines which further contribute in exacerbating the symptoms. Inefficient
      antigen presentation in these patients might add another parameter while looking
      at the severity of disease.

PMID- 26201789
TI  - Impact of combined therapy with alpha-lipoic and ursodeoxycolic acid on
      nonalcoholic fatty liver disease: double-blind, randomized clinical trial of
      efficacy and safety.
AB  - BACKGROUND AND PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is one of the
      causes of a fatty liver, occurring when fat is deposited (steatosis) in the liver
      not due to excessive alcohol use. It is related to insulin resistance and the
      metabolic syndrome. The purpose of the present study was to evaluate the impact
      of combination therapy with alpha-lipoic acid (ALA) and ursodeoxycholic acid
      (UDCA) on NAFLD. METHODS: Alpha-lipoic acid 400 mg/day plus UDCA 300 mg/day
      (ALAUDCA) was investigated in patients over a period of 12 months using a
      randomized, placebo (PLA)-controlled study with four parallel groups. Serum
      concentration of gamma-glutamyl transpeptidase (GGT), alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), albumin and platelets (PLT) were
      measured at the beginning and at the end of the treatment. Moreover, the AST/ALT
      ratio and the NAFLD fibrosis score were examined. RESULTS: A total of 120
      patients were randomly assigned to the four groups. ALA and UDCA were safe and
      well tolerated in the oral daily administration only. AST, ALT, GGT (p < 0.001)
      showed a significant difference between ALAUDCA and other three groups. Besides,
      NAFLD fibrosis score underlined a significant reduction (p < 0.04) in the ALAUDCA
      group, while AST/ALT ratio presented a moderate decline (p > 0.05). CONCLUSION:
      ALAUDCA therapy reduced AST, ALT, GGT values and improved NAFLD fibrosis score
      and AST/ALT ratio, especially in patients who were on a hypocaloric diet. These
      findings will be useful in patient selection in future clinical trials with
      ALAUDCA in long-term studies.

PMID- 26201790
TI  - The influence of pioglitazone on the plasma amino acid profile in patients with
      nonalcoholic steatohepatitis (NASH).
AB  - BACKGROUND AND AIMS: The peroxisome proliferator-activated receptor-gamma (PPAR
      gamma) ligand, piglitazone, enhances the degradation of branched-chain amino
      acids (BCAAs) in adipose tissue. However, it remains unknown whether pioglitazone
      influences the plasma amino acids (AA) profile in patients with nonalcoholic
      steatohepatitis (NASH). Thus, we investigated the relation between the
      therapeutic effect and the AA profile in NASH patients with a prospective study.
      METHODS: We randomized 25 histologically proven NASH patients to diet treatment
      only or diet treatment plus pioglitazone (15 mg/day), and investigated the
      biological data for 24 months. We measured the concentrations of AAs and compared
      them between the beginning and the end of the study. RESULTS: Compared with the
      diet only group, pioglitazone therapy was associated with an increase in body
      weight (mean change -1.03 vs. +3.8 kg; p = 0.027) and subcutaneous fat (-3.7 vs.
      +45.7 cm(2); p = 0.056), and decreased ALT levels (-0.6 vs. -38.4 IU/L; p =
      0.029) and HbA1c (0.33 vs. -0.29 %; p = 0.016). Regarding the AA profile, L
      isoleucine, L-leucine, L-histidine, and L-lysine were significantly reduced in
      patients treated with pioglitazone. Furthermore, L-leucine was significantly
      reduced compared with those in the diet only group (mean change -34.8 vs. +4.12
      nmol/mL; p = 0.032). Interestingly, there was a significant correlation between
      the changes in BCAAs, especially L-leucine, and those in ALT regardless of
      treatment with pioglitazone. CONCLUSIONS: Pioglitazone therapy in NASH subjects
      significantly reduced the plasma BCAA level and the degradation was closely
      related to the improvement of the ALT levels. These results suggest that
      pioglitazone improves insulin resistance and BCAA metabolism in NASH patients.

PMID- 26201791
TI  - Insulin resistance, inflammation, and nonalcoholic fatty liver disease in non
      obese adults without metabolic syndrome components.
AB  - PURPOSE: The purpose of the present study was to examine the association of
      insulin resistance and inflammation with nonalcoholic fatty liver disease (NAFLD)
      in non-obese adults without metabolic syndrome components. METHODS: This was a
      cross-sectional study of 759 subjects aged 50 years and older. Diagnosis of NAFLD
      was based on sonographic evidence of fatty liver without significant alcohol
      consumption and another cause of chronic liver disease. Subjects without
      metabolic syndrome components were defined as having none of the following: high
      blood pressure (>=130/85 mmHg), elevated fasting glucose (>=100 mg/dl),
      hypertriglyceridemia (>=150 mg/dl), low high-density lipoprotein-cholesterol (men
      <40 mg/dl; women <50 mg/dl), and abdominal obesity measured by waist
      circumference >=90 cm for men and >=80 cm for women. The subjects were divided
      into quartile groups according to levels of high-sensitivity C-reactive protein
      (hs-CRP), homeostasis model assessment of insulin resistance (HOMA-IR), and uric
      acid. Odds ratios (ORs) were computed for each quartile relative to the lowest
      quartile group. RESULTS: After adjustment for age, sex, smoking status, regular
      exercise, hs-CRP, HOMA-IR, and uric acid, a significant association was found
      between NAFLD and higher levels of hs-CRP, HOMA-IR, and uric acid. After
      adjustment for age, sex, smoking status, regular exercise, hs-CRP, HOMA-IR, and
      uric acid, the Ors (95 % confidence interval) of NAFLD with the highest quartile
      of hs-CRP, HOMA-IR, and uric acid compared with the lowest quartile were 2.58
      (1.03-6.50), 2.55 (1.08-6.05), and 5.15 (1.78-14.89), respectively. CONCLUSIONS:
      Insulin resistance and inflammation are independently associated with NAFLD in
      non-obese adults without metabolic syndrome components.

PMID- 26201792
TI  - The Fatty Liver Index has limited utility for the detection and quantification of
      hepatic steatosis in obese patients.
AB  - PURPOSE: Noninvasive tools for the detection of hepatic steatosis are needed. The
      Fatty Liver Index (FLI), which includes body mass index (BMI), waist
      circumference, triglycerides, and gamma-glutamyl-transferase, has been proposed
      as a screening tool for fatty liver. Our objective was to validate the FLI for
      the detection and quantification of hepatic steatosis in an obese population.
      METHODS: Patients with chronic liver disease and BMI >= 28 kg/m(2) underwent
      liver biopsy and FLI determination. FLI performance for diagnosing steatosis
      compared with biopsy was assessed using areas under receiver operating
      characteristic curves (AUROCs), and a novel model for the prediction of
      significant steatosis (>=5 %) was derived. RESULTS: Among 250 included patients,
      65 % were male, and the median BMI was 33 kg/m(2); 48 % had nonalcoholic fatty
      liver disease, and 77 % had significant (>=5 %) steatosis. The FLI was weakly
      correlated with the percentage (rho = 0.25, p = 0.0001) and grade of steatosis
      (rho = 0.28, p < 0.00005). The median FLI was higher among patients with
      significant steatosis (91 vs. 80 with <5 % steatosis; p = 0.0001) and the AUROC
      for this outcome was 0.67 (95 % CI 0.59-0.76). At an optimal FLI cut-off of 79,
      the FLI was 81 % sensitive and 49 % specific, and had positive and negative
      predictive values of 84 and 43 %, respectively. A novel index including
      triglycerides, glucose, alkaline phosphatase, and BMI outperformed the FLI for
      predicting significant steatosis [AUROCs 0.78 vs. 0.68; p = 0.009 (n = 247)].
      CONCLUSIONS: In obese patients, the FLI is a poor predictor of significant
      steatosis and has limited utility for steatosis quantification compared with
      liver histology. A novel index including triglycerides, glucose, alkaline
      phosphatase, and BMI may be useful, but requires validation.

PMID- 26201793
TI  - Amelioration of hepatic inflammation in a mouse model of NASH using a
      dithiocarbamate derivative.
AB  - PURPOSE: The process whereby liver inflammation develops in non-alcoholic
      steatohepatitis (NASH) is not fully understood. While modification of the
      inflammatory milieu is an attractive target to prevent the development of
      hepatocellular injury, most antiinflammatory agents have proven ineffective in
      this setting. Tetraethylthiuram disulfide (TDSF) is able to induce S
      glutathionylation of NF-kappaB along with critical signaling proteins involved
      with inflammation, especially when complexed with a heavy metal. For this reason,
      we hypothesized that administration of TDSF would function to ameliorate
      necroinflammatory activity in a mouse model of NASH. METHODS: Mice were divided
      into five groups and received control chow versus a methionine-choline-deficient
      diet. After 6 weeks of TDSF versus sham gavage, animals were necropsied. Using
      conventional H&E staining, livers were examined using the Brunt scoring system by
      a hepatopathologist blinded to treatment groups. Validated mouse primer sets were
      used for quantitative real-time PCR to evaluate changes in mRNA expression.
      RESULTS: Livers treated with TDSF demonstrated a qualitative reduction in lobular
      inflammation, lipogranuloma formation, and Kupffer cell accumulation, but not
      steatosis. Significant reductions in inflammatory transcripts for alpha-1
      collagen, TGF-beta, Mmp2, MCP-1, and TNF-1alpha were also observed. CONCLUSIONS:
      Animals treated with TDSF exhibit a reduction in lobular inflammation that is
      independent of lipid accumulation when administered MCD diet. Similar reductions
      are seen in several inflammatory transcripts associated with NASH. Additional
      work in this area may reveal a therapeutic role for TDSF or similar agents in
      curtailing inflammatory signaling within the liver.

PMID- 26201794
TI  - Fatty liver score and 15-year incidence of type 2 diabetes.
AB  - PURPOSE: Both non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL)
      are strongly associated with obesity, metabolic syndrome, and type 2 diabetes
      mellitus (T2DM). Recently, also the vitamin D level has been associated with
      these and may also be associated with fatty liver (FL). Liver function tests
      (LFTs) are insensitive markers of FL, but use of scores may help in identifying
      subjects with FL. We studied how LFTs and the FL score predict the development of
      T2DM in subjects with AFL versus NAFL and low versus high vitamin D levels.
      METHODS: A cohort study based on 4,517 participants, aged 40-79, from the
      representative Mini-Finland Health Survey was carried out. During a follow-up of
      15 years, 217 T2DM cases occurred. LFTs were determined from serum samples, and
      the FL score was formed using BMI, fasting glucose, HDL cholesterol, and GGT
      concentrations. RESULTS: The risk of T2DM incidence in the highest versus lowest
      quartile was twofold for the LFTs and ninefold for the FL score. A total of 77 %
      (95 % confidence interval: 57-87 %) of the T2DM cases could have been prevented
      if all individuals' FL scores had been at the level of the first quartile. Heavy
      alcohol consumption and low serum vitamin D concentrations were associated with
      an increased risk of T2DM among individuals with high FL scores. CONCLUSIONS: The
      FL score is a useful tool for diagnosing FL in epidemiological studies. A high FL
      score predicts increased risk of T2DM, especially when combined with heavy
      alcohol consumption or low vitamin D levels.

PMID- 26201795
TI  - Nitric oxide and prostaglandin as mediators in the pathogenesis of hyperkinetic
      circulatory state in a model of endotoxemia-induced portal hypertension.
AB  - AIMS: To evaluate the participation of nitric oxide (NO) and prostaglandin (PGI2)
      on hyperdynamic state in endotoxemia-induced portal hypertension (EIP) induced by
      chronic endotoxemia. METHODS: The portal pressure (PP) and mean arterial pressure
      (MAP) were recorded, in vivo before and after administration of L-NAME (NOS
      inhibitor) and indomethacin (specific blocker of COX). The vasoactive responses
      to acetylcholine of thoracic rat aortic rings were studied in vitro before and
      after nitric oxide and cyclooxygenase blockade using multichannel organ bath. The
      mRNA expression for isoforms of (cyclooxygenase) COX and nitric oxide synthase
      (NOS) were analyzed using RT-PCR. RESULTS: Administration of both L-NAME and
      indomethacin in EIP rabbits significantly reduced (p < 0.05) the PP and reversed
      the MAP to normal as compared to sham-operated (SO) rabbits. There was impaired
      vasodilatory response to acetylcholine in EIP rabbits. L-NAME caused a
      significant reduction in acetylcholine-induced vasorelaxation in SO rabbits than
      EIP due to preexisting hyperemia in EIP. Indomethacin partially restored
      vasoresponsiveness to acetylcholine in EIP group. The mRNA expression of eNOS
      (endothelial NOS) and COX-1 (constitutive COX) were significantly higher in SO
      than EIP rabbits. iNOS (inducible NOS) and COX-2 (inducible COX) mRNA expression
      was seen only in EIP rabbits. CONCLUSIONS: A significant component of
      acetylcholine-mediated vasorelaxation in EIP model is modulated by eNOS. There
      was increased production of contractile prostaglandin in EIP rabbits. iNOS and
      COX-2 play an important role in the hemodynamic abnormalities of PHT. This novel
      model of PHT produced by chronic splanchnic endotoxemia in rabbit, mimics
      impaired vasodilation and vasoreactivity akin to other models of PHT.

PMID- 26201796
TI  - Percutaneous transhepatic variceal embolization with cyanoacrylate vs.
      transjugular intrahepatic portal systematic shunt for esophageal variceal
      bleeding.
AB  - PURPOSE: To compare the long-term results of modified percutaneous transhepatic
      variceal embolization with cyanoacrylate (PTVE) and the transjugular intrahepatic
      portal systemic shunt (TIPS) for treating esophageal variceal bleeding. METHODS:
      Patients with cirrhosis and variceal bleeding who underwent TIPS and PTVE with
      cyanoacrylate between January 2006 and December 2010 were selected. We performed
      chart reviews to determine the rebleeding rate, survival and the rate of
      encephalopathy. RESULTS: This retrospective study included 96 PTVE patients and
      43 TIPS patients, with a median follow-up of 30.4 and 31.6 months in the two
      groups, respectively. Rebleeding occurred in 13 patients (30.2 %) in the TIPS
      group and in 20 patients (20.8 %) in the PTVE group (p = 0.229). For patients
      with model for end-stage liver disease (MELD) scores >18 at 1, 3 and 5 years, the
      survival rates were 84.2, 39.9 and 16.0 %, respectively, in the TIPS group, and
      they were 96.7, 72.0 and 36.0 %, respectively, in the PTVE group (p = 0.037).
      Sixteen (16.7 %) PTVE patients and 25 (58.1 %) TIPS patients developed
      encephalopathy (p = 0.000). Mean MELD and Child-Pugh scores improved
      significantly in modified PTVE patients. However, no such changes were observed
      in TIPS patients. CONCLUSIONS: PTVE and TIPS were comparable in terms of variceal
      rebleeding prevention. However, in >18-MELD-score patients, PTVE offered better
      survival than TIPS. In addition, PTVE offered lower incidence of encephalopathy
      than TIPS.

PMID- 26201797
TI  - Alcoholism worsens the survival of patients with hepatitis B virus and C virus
      related hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Chronic hepatitis B and hepatitis C virus (HBV, HCV) infection
      and alcoholism are common etiologies for hepatocellular carcinoma (HCC). The
      characteristics and impact of alcoholism and/or HCV/HBV infection on HBV- and HCV
      related HCC, respectively, are investigated in this study. METHODS: A total of
      1,888 patients were retrospectively investigated and categorized into six groups,
      HBV only (n = 977), HBV with alcoholism (n = 197), HCV only (n = 544), HCV with
      alcoholism (n = 67), dual HBV and HCV (n = 82), and dual virus with alcoholism (n
      = 21), to examine their interactions on the outcome. RESULTS: Compared to their
      counterparts, alcoholic patients coinfected with HBV and/or HCV tended to be
      younger, had higher male-to-female ratios, worse performance status, more severe
      liver cirrhosis, advanced cancer staging, and tumor burden than patients without
      alcoholism. In survival analysis, patients with HBV with alcoholism had a
      significantly decreased survival than the HBV-only group (p = 0.001). A shortened
      survival was also observed in HCV with alcoholism group compared to the HCV-only
      group (p = 0.011). Dual virus infection with alcoholism did not significantly
      worsen the survival compared to the dual virus infection group. In the Cox
      proportional hazards model, HBV with alcoholism group [risk ratio (RR) 1.299, p =
      0.032] and HCV with alcoholism (RR 1.523, p = 0.025) group were independent
      predictors associated with decreased survival compared to their counterpart of
      HBV- and HCV-only groups. CONCLUSIONS: Alcoholism in patients with HBV or HCV
      infection is characterized by early development of HCC with advanced cirrhosis
      and cancer staging at diagnosis. Alcoholism independently predicts an increased
      risk of mortality in patients with HBV- and HCV-related HCC.

PMID- 26201798
TI  - The expression of transporter OATP2/OATP8 decreases in undetectable
      hepatocellular carcinoma by Gd-EOB-MRI in the explanted cirrhotic liver.
AB  - PURPOSE: The aim of this study is to evaluate the detectability of hepatocellular
      carcinoma (HCC) in the explanted cirrhotic liver using gadoxetic acid-enhanced
      magnetic resonance imaging (Gd-EOB-MRI) and the degree of organic anion
      transporter OATP2/OATP8 (OATP1B1/1B3) HCC which could not be preoperatively
      detected by multi-detector computed tomography (MD-CT) and Gd-EOB-MRI. METHODS:
      Eleven patients (HBV 3, HCV 7, nonBnonC 1) out of 145 recipients of liver
      transplantation were analyzed. The detectability by each imaging modality and the
      expression of OATP2/OATP8 of HCC were analyzed using the whole liver thin sliced
      histological and immunohistochemical examination retrospectively. RESULTS: The
      imaging examination detected 17 lesions of HCC by MDCT and/or Gd-EOB-MRI. Only
      one lesion detected by Gd-EOB-MRI had well differentiated and minute (7 mm) HCC.
      However, the histological examination revealed newly 11 lesions and one false
      positive lesion of HCC in the explanted livers. The median diameter of the
      preoperatively undetectable HCC by imaging was 8 mm (2-12). The histological
      characteristic of the preoperatively undetectable HCC was well differentiated HCC
      (10/11). The accuracy rate in MDCT and Gd-EOB-MRI was 53.6 % (15/28) and 57.1 %
      (16/28). The rate of positive predictive value in MDCT and Gd-EOB-MRI was 93.7 %
      (15/16) and 94.2 % (16/17), respectively. The expression of OATP2/OATP8 in the
      preoperatively undetectable HCC was negative in nine lesions, was weak positive
      in two lesions. CONCLUSIONS: The detectability of Gd-EOB-MRI is almost equal to
      MDCT in a cirrhotic liver. Small HCCs were difficult to detect even with Gd-EOB
      MRI. The transporter of OATP2/OATP8 was less expressed in the preoperatively
      undetectable HCCs.

PMID- 26201799
TI  - Diffusion-weighted imaging of hepatocellular carcinoma for predicting early
      recurrence and survival after hepatectomy.
AB  - PURPOSE: The effectiveness of imaging (including apparent diffusion coefficient
      [ADC] of diffusion-weighted magnetic resonance imaging [DWI]) and laboratory
      variables for predicting early tumor recurrence and overall survival after
      surgery in hepatocellular carcinoma (HCC) patients are analyzed. METHODS: The
      present study included 116 consecutive patients with HCC who underwent partial
      hepatectomy. Patients were classified into two groups: patients with and without
      early recurrence (<1 year). Preoperative imaging variables (tumor number, size,
      shape, capsule, ADC, and venous invasion) and laboratory variables were evaluated
      to predict early recurrence using univariate and multivariate analyses. Overall
      survival was calculated using the Kaplan-Meier method. RESULTS: Twenty patients
      (17 %) developed early recurrence after surgery. Multivariate logistic regression
      analysis showed that tumor ADC (p = 0.0002), aspartate aminotransferase (p =
      0.0121), and serum prothrombin time activity percentage (p = 0.0082) were
      statistically significant for predicting early recurrence. The optimal ADC cutoff
      value for predicting early recurrence obtained from receiver operating
      characteristic analysis was <=0.898 * 10(-3) mm(2)/s. In patients with ADC
      <=0.898 * 10(-3) mm(2)/s, the 3- and 5-year survival rates (77 and 56 %,
      respectively) were significantly decreased compared with those in patients with
      ADC >0.898 * 10(-3) mm(2)/s (97 and 97 %, respectively; p = 0.0015). CONCLUSIONS:
      Low tumor ADC value by DWI was a risk factor for early postoperative HCC
      recurrence and was associated with lower patient survival rates.

PMID- 26201800
TI  - p53 codon 72 polymorphism and hepatocellular carcinoma: a meta-analysis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant
      neoplasms worldwide. The p53 gene is frequently mutated in some histological
      subtypes of HCC. The role of p53 mutations and polymorphic variant of codon 72 in
      the prognosis of disease is still unclear. The p53 tumor suppressor gene Arg72Pro
      polymorphism has been associated with HCC. However, results were inconsistent.
      This meta-analysis was performed to estimate the association between p53 Arg72Pro
      polymorphism and HCC or HCC infected by HBV/HCV. METHODS: Electronic search of
      PubMed was conducted to select studies. Studies containing available genotype
      frequencies of Arg72Pro were chosen, and pooled odds ratio (OR) with 95 %
      confidence interval (CI) was used to assess the association. RESULTS: Ten
      published studies, including 1,371 HCC cases and 2,517 controls were identified.
      The overall results suggested that the variant genotypes were associated with the
      HCC risk (Pro/Pro vs. Pro/Arg + Arg/Arg: OR 1.355, 95 % CI 1.041-1.764, p =
      0.024). In the stratified analysis, individuals with the Pro/Pro in the recessive
      model had increased risk of HCC (OR 1.927, 95 % CI 1.127-3.297, p = 0.017) in
      Caucasian. A symmetric funnel plot, the Begg's test, was suggestive of the lack
      of publication bias. There was no association between the p53 codon 72
      polymorphism and HBV/HCV-positive HCC. CONCLUSION: This meta-analysis suggests
      that p53 condon 72 Pro/Progenotypes are associated with increased risk of HCC in
      Caucasian. To validate this association, further studies with larger participants
      worldwide are needed to examine the associations between this polymorphism and
      HCC.

PMID- 26201801
TI  - Is transarterial chemoembolization beneficial for patients with diffuse
      infiltrative hepatocellular carcinoma?
AB  - PURPOSE: Diffuse infiltrative hepatocellular carcinoma (D-HCC) is an incurable
      disease with short survival time. Transarterial chemoembolization (TACE) was
      often used to alleviate patient's symptoms and reduce tumor burden. However, it
      remains unknown if the TACE benefits the survival of D-HCC patients. METHODS: A
      hospital-based retrospective study was conducted at a large referral hospital in
      Taiwan for a 9-year period (2000-2008). RESULTS: Of the 150 D-HCC patients, 106
      patients were related to hepatitis B virus (HBV), 17 to hepatitis C virus (HCV),
      3 to both HBV and HCV, and 24 not to HBV or HCV. Multivariate Cox regression
      analysis showed treatment strategy, serum alpha-fetoprotein level, model for end
      stage liver disease (MELD) score, serum gamma glutamyl transferase, and serum
      lactic acid dehydrogenase were associated with survival time. Compared to
      supportive treatment, the adjusted hazard ratios of transarterial
      chemoembolization (TACE) and chemotherapy including oral or systemic chemotherapy
      were 0.383 (p < 0.001) and 0.711 (p = 0.289), respectively. CONCLUSION: TACE is a
      preferred therapy for D-HCC patients.

PMID- 26201802
TI  - SNPs in the promoter region of the osteopontin gene as a possible host factor for
      sex difference in hepatocellular carcinoma development in patients with HCV.
AB  - AIMS: Four single nucleotide polymorphisms (SNPs) exist in the promoter region of
      the osteopontin (OPN) gene, namely, the SNPs at nucleotide (nt) -155, -616, and 
      1748 showing linkage disequilibrium to each other, and an independent SNP at nt 
      443. The significance of these SNPs in the risk of hepatocellular carcinoma (HCC)
      development was examined in patients with hepatitis C virus (HCV). METHODS: The
      SNPs at nt -155 and nt -443 were analyzed in 120 patients with HCC. The promoter
      activity was measured in HepG2 cells by the dual-luciferase reporter assay. The
      electrophoretic mobility shift assay was performed using nuclear extracts from
      the cells. RESULTS: Peripheral platelet counts at the time of HCC detection were
      greater in women with homozygous deletion at nt -155 and C/C or C/T at nt -443
      than in those showing other allelic combinations, while no such difference was
      observed in men. The promoter activity was greater in oligonucleotides with
      deletions at nt -155 and C at nt -443 than in those with other haplotypes. The
      mobility shift assay showed double and single complexes with oligonucleotides
      around nt -155 and nt -443, respectively. Binding activities were greater in
      deletion than in G in the case of the retarded complex in the former assay and in
      T than in C in the latter assay. The other complex in the former assay included
      SRY, showing an equivalent binding activity to oligonucleotides with both
      alleles. CONCLUSION: OPN promoter SNPs may play a role in the sexual difference
      in the risk of HCC development through the regulation of OPN expression in
      patients with HCV.

PMID- 26201803
TI  - Type 2 diabetes, smoking, insulin use, and mortality from hepatocellular
      carcinoma: a 12-year follow-up of a national cohort in Taiwan.
AB  - BACKGROUND: The effect of smoking and insulin use in the association between
      diabetes and hepatocellular carcinoma (HCC) is not known. MATERIALS AND METHODS:
      Age-standardized HCC mortality trends during 1995-2006 in the general population
      were calculated. A total of 88,694 type 2 diabetic patients aged >=25 years
      recruited in 1995-1998 were followed till 2006. Age- and sex-specific mortality
      rates and the mortality rate ratios (vs. the average mortality rates in the
      general population) were calculated. Risk factors were evaluated by Cox
      regression. RESULTS: The age-standardized mortality trend slightly increased
      significantly in women but was steady in men. For diabetic patients aged >=25
      years, 830 men and 515 women died of HCC during 1995-2006. Mortality rate ratios
      (95 % confidence interval) were larger with the decreasing age: 7.36 (6.52,
      8.31), 2.48 (2.22, 2.78), 1.79 (1.59, 2.02), and 1.87 (1.51, 2.32) for age 25-54,
      55-64, 65-74, and >=75 years for men, respectively, 10.12 (7.73, 13.25), 4.08
      (3.57, 4.67), 2.45 (2.15, 2.78), and 1.71 (1.34, 2.19) for women. Age, male sex,
      lower BMI, smoking, and insulin use were associated with HCC mortality, but
      diabetes duration was not. Smoking and insulin use carried a significantly higher
      risk of 22-29 % and 37-58 %, respectively, without interaction. A dose-responsive
      pattern between the duration of insulin use and HCC mortality was noted, with a
      relative risk of 1.5-1.7 in those who used insulin for >=10 years. CONCLUSIONS:
      Diabetic patients have a higher risk of HCC mortality, which is more remarkable
      in the younger age. Smoking and insulin are potentially modifiable risk factors.

PMID- 26201804
TI  - Initial response to sorafenib by using enhancement criteria in patients with
      hepatocellular carcinoma.
AB  - PURPOSE: Sorafenib induces early vascularity reduction in patients with
      hepatocellular carcinoma (HCC). We sought to identify differences in radiological
      assessment approaches and to evaluate their usefulness for the prediction of the
      initial response to sorafenib. METHODS: Forty-eight patients with advanced HCC
      treated with sorafenib were evaluated by four-phase contrast-enhanced computed
      tomography. All target lesions were analyzed using the Response Evaluation
      Criteria in Solid Tumors (RECIST), the EASL criteria, and modified RECIST
      (mRECIST). RESULTS: At the initial evaluation at 4-6 weeks, rates of objective
      response (OR) (including both complete and partial responses), stable disease
      (SD), and progressive disease (PD) were 2, 71, and 27 %, respectively, according
      to RECIST; 15, 56, and 29 %, respectively, according to the EASL criteria; and
      15, 58, and 27 %, respectively, according to mRECIST. Patients who achieved an OR
      according to the EASL criteria also achieved an OR according to mRECIST. Patients
      who achieved an OR according to the EASL criteria or mRECIST had better predicted
      overall survival (OS) than did patients who achieved SD (p = 0.033 and 0.028,
      respectively). Patients with SD according to RECIST had different outcomes
      depending on the response according to enhancement criteria. Patients classified
      as responders (complete and partial) had better predicted OS than those
      classified as non-responders (those classified as SD and PD) (p = 0.048).
      CONCLUSIONS: The enhancement criteria could be useful for prediction of the
      initial response to sorafenib in patients with HCC. Moreover, mRECIST appears to
      be simple and convenient.

PMID- 26201805
TI  - Changing etiology of liver failure in 3,916 patients from northern China: a 10
      year survey.
AB  - PURPOSE: To investigate the etiological characteristics of patients with liver
      failure in the past 10 years. METHODS: Clinical and investigational data in
      hospitalized patients with liver failure admitted from 2002 to 2011 were
      retrospectively analyzed. Standard definitions and criteria were used to assess
      disease etiology. RESULTS: Of these 3,916 patients, 3,429 (87.6 %) had acute-on
      chronic liver failure (ACLF), 114 (2.9 %) acute liver failure (ALF), and 373 (9.5
      %) subacute liver failure. Viral infection was the most common cause of liver
      failure in the 3,295 patients (84.1 %). Hepatitis of unknown etiology was deemed
      responsible for 371 cases of liver failure (9.5 %). Drug-induced liver injury,
      alcoholic hepatitis, and autoimmune hepatitis led to 120 cases (3.1 %), 109 cases
      (2.8 %), and 19 cases (0.5 %), respectively. The most common cause of ACLF was
      HBV infection (87.3 %), while the main causes of acute and subacute liver failure
      were hepatitis of unknown etiology (39.4 %), viral infection (36.6 %), and drug
      induced liver injury (19.3 %). Our data showed that the incidence of liver
      failure caused by HBV gradually decreased from 86.5 % in 2002 to 69.2 % in 2011.
      However, the incidence of hepatitis of unknown etiology, drug-induced liver
      injury, and alcoholic hepatitis was increased. CONCLUSIONS: HBV infection is the
      main cause of liver failure in China. However, the incidence of HBV-related liver
      failure has gradually decreased in the past 10 years. Hepatitis of unknown
      etiology has replaced HBV infection as the most common apparent cause of acute
      liver failure.

PMID- 26201806
TI  - Cell-free DNA as a potential marker to predict carbon tetrachloride-induced acute
      liver injury in rats.
AB  - PURPOSE: Finding an optimal biomarker for the noninvasive evaluation of acute
      liver injury (ALI) may be of great value in predicting clinical outcomes and
      investigating potential treatments. We investigated cell-free DNA (CFD) as a
      potential biomarker to predict carbon tetrachloride-induced ALI in rats. METHODS:
      Forty-five Sprague-Dawley rats were randomly assigned to three groups. ALI was
      induced by carbon tetrachloride via a nasogastric tube at 1, 2.5, or 5 ml/kg of a
      50 % solution. Fifteen additional rats underwent a sham procedure. Blood samples
      were drawn at time t which was 0 (baseline), 3, 6, 12, 24, 48, 72, 96, and 120 h
      for the measurements of CFD, glutamate-pyruvate transaminase (GPT), glutamate
      oxaloacetate transaminase (GOT), and total bilirubin. Prothrombin time and
      histology were examined at 24 and 120 h following injection of 5 ml/kg carbon
      tetrachloride in 18 additional rats and in 10 control rats. RESULTS: CFD levels
      in rats subjected to carbon tetrachloride-induced ALI were significantly
      increased in all blood samples starting at 12 h after the induction of ALI (p <
      0.001), reaching peak levels at 24 h. Blood GOT, GPT, and total bilirubin were
      elevated in all blood samples starting at 3 h after the induction of ALI (p <
      0.0001), reaching peak levels by 48 h. A positive correlation was demonstrated
      between CFD levels and GOT (R (2) = 0.92), GPT (R (2) = 0.92), and total
      bilirubin (R (2) = 0.76). CFD levels correlated with liver damage seen on
      histological examination, as well as predicted liver damage, at 24 h after ALI.
      CONCLUSIONS: CFD may be a useful biomarker for the prediction and measurement of
      ALI. There is no evidence to suggest that CFD is superior to other available
      noninvasive biomarkers.

PMID- 26201807
TI  - Short- and long-term outcomes of third liver transplantation at single centre.
AB  - PURPOSE: Although three or more liver transplantation (LT)s in the same patient
      arouse not only medical but also ethical issues in the context of organ shortage,
      it is a fact that additional liver retransplantation (reLT) is the only
      lifesaving treatment option for those with graft failure after a second LT.
      However, little is known regarding the risks and benefits associated with a third
      LT. METHODS: We analyzed fifteen cases of third LT and 48 of second LT performed
      between January 2000 and December 2010. Clinical outcomes were compared with
      those of second LT cases performed during the same period. RESULTS: Model for end
      stage liver disease (MELD) scores at transplant was similar between the two
      groups. As for surgical aspects, there was no significant difference in operative
      time or number of units of red blood cells transfused during the transplant
      procedures between the groups. Patient and graft survival after the third LT at
      1, 3, and 10 years were 66.7, 51.9, and 44.4 %, and 66.7, 51.9, and 29.6 %,
      respectively. There was no significant difference in patient or graft survival
      between the groups. However, graft loss within 3 months after the third LT was
      significantly higher than that of second LT patients. CONCLUSION: Third LT cases
      showed acceptable short- and long-term outcomes that were not significantly
      inferior to those of a second LT. Careful patient care especially in the early
      phase after a third LT may be essential to improve the outcome.

PMID- 26201808
TI  - Remnant left liver size and recovery of living right liver donors.
AB  - PURPOSE: Living donor liver transplantation is a realistic life-saving treatment
      in regions where deceased donor organs are scarce. The minimum remnant left liver
      volume (RLLV) requirement for donor right hepatectomy (DRH) varies in different
      programs of living donor liver transplantation. The present study aimed to
      determine how significant the RLLV is in the recovery of right liver donors.
      METHOD: A total of 349 consecutive donors who underwent DRH including the middle
      hepatic vein were divided into nine groups according to the percentage of the
      RLLV. The peak and recovery of the serum bilirubin level and prothrombin time
      (PT) in the 1st week after operation and postoperative complications were
      studied. RESULTS: The median RLLV was 35.5 (27-49.5) %. Postoperative peak serum
      bilirubin was highest [74 (25-133) MUmol/L] in the group with RLLVs <30 %. This
      group also had the highest peak PT [18.9 (15.4-24.4) s], although results were
      similar between groups. Total bilirubin peaked on postoperative days 1-2 in
      groups with RLLVs >=35 %. In groups with RLLVs <35 %, total bilirubin peaked on
      day 3. PT took 1-2 days to peak and nearly approached preoperative values on day
      7 in all groups. Complication rates ranged from 0 to 75 %. The rates of
      complications of Clavien-Dindo grade 3 or above ranged from 0 to 3.8 %.
      Postoperative peak bilirubin was associated with severe complications (p =
      0.031). Age, postoperative peak PT, and RLLV were independent risk factors for
      prolonged hospital stay. CONCLUSION: There was a demonstrable trend of slower
      recovery of liver function in donors with smaller RLLVs.

PMID- 26201809
TI  - Ethnicity predicts metabolic syndrome after liver transplant.
AB  - PURPOSE: Post-transplant metabolic syndrome (PTMS) is associated with important
      causes of morbidity and mortality in solid organ transplant recipients. Our aim
      was to investigate predictors of PTMS in liver transplant (LT) recipients.
      METHODS: We randomly selected 343 adults (>18 years of age) from a large cohort
      of 1,262 ethnically diverse patients who received LTs during 2000-2010. RESULTS:
      Of 343 patients included, 68.2 % were male, with a mean age of 54 +/- 10 years,
      87 % White, and 31 % Hispanic. Prior to LTs, 6.2 % were on lipid-lowering agents
      and 24.5 % had BMI >= 30 (mean 26.9 +/- 5 kg/m(2)). More Hispanics had diabetes
      before LTs compared to non-Hispanics (p = 0.037). Among those with follow-up of
      >6 months (n = 304) after LTs, the proportion of patients with diabetes and
      hypertension increased from 21.9 to 27 % (p < 0.0001), and from 11.5 to 51.6 % (p
      < 0.0001), respectively. Cholesterol levels increased from 150 +/- 115 to 167 +/-
      70 (p < 0.0001). BMI remained unchanged. PTMS developed in 41 (13.5 %) and
      cardiovascular events in 31 (10.2 %) patients. Hispanics had higher risk of
      developing PTMS compared to non-Hispanics (OR 2.30, 95 % CI 1.18-4.49). Survival
      was not affected by PTMS (p = 0.3), ethnicity (p = 0.52), or nonalcoholic
      steatohepatitis as the etiology of liver disease (p = 0.50). CONCLUSIONS: More
      Hispanics had diabetes before LTs (29 to 18 %, p < 0.05) and were more prone to
      developing PTMS after LTs compared to non-Hispanics.

PMID- 26201810
TI  - Magnitude of contrast-enhanced ultrasonography as a noninvasive predictor for
      hepatic fibrosis: comparison with liver stiffness measurement and serum-based
      models.
AB  - PURPOSE: To elucidate the efficiency of contrast-enhanced ultrasonography alone
      and in combination with other noninvasive models for grading hepatic fibrosis.
      METHODS: This prospective study included 74 patients with four grades (F1-F4) of
      chronic liver disease (17, 20, 18, and 19 patients, respectively). Diagnostic
      performances of the contrast parameter (time to the maximum intensity ratio
      between the right portal vein and liver parenchyma from the onset of contrast
      enhancement in the right portal vein) assessed by ultrasonography, liver
      stiffness measurement (LSM), FIB-4 test, and type IV collagen 7s were compared
      with histological findings. RESULTS: Greatest areas under the receiver operating
      characteristics curve (Az) with the single model were 0.83 (95 % confidence
      interval 0.71-0.91) for marked fibrosis (>=F2) by FIB-4 test; 0.85 (0.73-0.92)
      for advanced fibrosis (>=F3) by LSM, and 0.92 (0.83-0.96) by type IV collagen 7s
      for cirrhosis (F4). When combined, Az for marked fibrosis was >=0.82; the best Az
      value was 0.87 (0.74-0.94) for the combination of contrast parameter with FIB-4.
      Similarly, the Az for advanced fibrosis was >=0.82, and the best Az value was
      0.89 (0.78-0.94) for the combination of contrast parameter with LSM. The Az for
      cirrhosis was >=0.95, and the best Az was 0.99 (0.97-1.00) for the combination of
      contrast parameter with LSM. CONCLUSIONS: The contrast parameter is a promising
      predictor for grading hepatic fibrosis when combined with LSM or FIB-4.

PMID- 26201811
TI  - Optimal preservation of liver biopsy samples for downstream translational
      applications.
AB  - OBJECTIVE: Molecular analysis of liver biopsy samples from patients requires
      ideal tissue preservation and handling to yield suitable material for laboratory
      analysis. Biopsy size, tissue handling and preservation method all may affect the
      quality and quantity of DNA, RNA and protein that can be extracted from liver
      biopsy samples. METHOD: In the present study, murine liver biopsies were
      performed and stored under various conditions: snap-freezing, RNAlater and
      Allprotect. Yield was compared to fresh biopsy tissue. RESULTS: Fresh tissue
      generated the highest yield of RNA while samples subjected to the snap-freezing
      generated the lowest yield of RNA. Preservation in RNAlater yielded higher
      quantities of RNA than storage in Allprotect, particularly with larger biopsy
      samples. There was a non-significant trend toward improved RNA quality with
      RNAlater (p = 0.35). DNA and protein yield were similar with RNAlater and
      Allprotect under a number of handling condition. Errors in tissue handling such
      as delays in tissue submersion or freezing did not significantly affect tissue
      yields in either preservation solution. Tissue yield was unchanged with up to
      three freeze-thaw cycles in both solutions. Biopsy size (5 vs 2 mm) and width (15
      vs 18 g) had a marked effect on tissue yield. CONCLUSION: Ideally 5-mm biopsies
      with 15-gauge needles should be used to maximize yield. RNAlater provided higher
      RNA yield with similar yields of DNA and protein and was notably cheaper and
      easier to handle.

PMID- 26201813
TI  - Loss of adaptation following reversion suggests trade-offs in host use by a seed
      beetle.
AB  - Experimental evolution has provided little support for the hypothesis that the
      narrow diets of herbivorous insects reflect trade-offs in performance across
      hosts; selection lines can sometimes adapt to an inferior novel host without a
      decline in performance on the ancestral host. An alternative approach for
      detecting trade-offs would be to measure adaptation decay after selection is
      relaxed, that is, when populations newly adapted to a novel host are reverted to
      the ancestral one. Lines of the seed beetle Callosobruchus maculatus rapidly
      adapted to a poor host (lentil); survival in lentil seeds increased from 2% to >
      90% in < 30 generations. After the lines had reached a plateau with respect to
      survival in lentil, sublines were reverted to the ancestral host, mung bean.
      Twelve generations of reversion had little effect on performance in lentil, but
      after 25-35 generations, the reverted lines exhibited lower survival, slower
      development and smaller size. The most divergent pair of lines was then assayed
      on both lentil and mung bean. Performance on lentil was again much poorer in the
      reverted line than in the nonreverted one, but the lines performed equally well
      on mung bean. Moreover, the performance of the nonreverted line on mung bean
      remained comparable to that of the original mung-bean population. Our results
      thus present a paradox: loss of adaptation to lentil following reversion implies
      a trade-off, but the continued strong performance of lentil-adapted lines on mung
      bean does not. Genomic comparisons of the reverted, nonreverted and ancestral
      lines may resolve this paradox and determine the importance of selection vs.
      drift in causing a loss of adaptation following reversion.

PMID- 26201812
TI  - Probiotics promote rapid-turnover protein production by restoring gut flora in
      patients with alcoholic liver cirrhosis.
AB  - BACKGROUND AND AIMS: Accumulating evidence suggests that deterioration of the gut
      flora contributes to the pathogenesis of alcoholic liver cirrhosis (ALC).
      However, the ALC flora profile and its response to probiotic treatment have not
      been fully examined. This double-blind placebo-controlled study aimed to evaluate
      whether the probiotic beverage Yakult 400 (Y400), which contains Lactobacillus
      casei strain Shirota, improves liver function in ALC patients, and to analyze the
      precise gut flora profile by real-time quantitative PCR (qPCR). METHODS: A total
      of 37 hospitalized ALC patients were randomly allocated to Y400 (n = 18) and
      placebo (n = 19) groups. Y400 or placebo was served twice a day during the first
      half of the four-week study. Serum concentrations of rapid-turnover proteins
      (i.e., transthyretin and transferrin), hypersensitive C-reactive protein, and
      interleukin-6 were measured weekly. qPCR analysis of fecal bacteria was performed
      biweekly; stocked fecal samples from 46 healthy subjects were used as references.
      RESULTS: Serum transthyretin levels significantly increased in the Y400 group in
      week 3; similar-although statistically insignificant-increases were seen for
      transferrin and albumin. Levels of hypersensitive C-reactive protein, but not
      interleukin-6, significantly decreased in week 4. Before treatment, populations
      of obligate anerobic bacteria were significantly smaller and those of
      Enterobacteriaceae were larger in patients than in healthy subjects examined in a
      previous study. Y400 corrected this imbalance. CONCLUSIONS: This is the first
      report describing the unique gut flora of ALC patients. Y400 treatment normalized
      the gut flora and improved liver function. These promising findings warrant
      further investigation in larger, multicenter studies.

PMID- 26201814
TI  - Resonance Raman Spectroscopic Analysis of the [NiFe] Active Site and the Proximal
      [4Fe-3S] Cluster of an O2-Tolerant Membrane-Bound Hydrogenase in the Crystalline
      State.
AB  - We have applied resonance Raman (RR) spectroscopy on single protein crystals of
      the O2-tolerant membrane-bound [NiFe] hydrogenase (MBH from Ralstonia eutropha)
      which catalyzes the splitting of H2 into protons and electrons. RR spectra taken
      from 65 MBH samples in different redox states were analyzed in terms of the
      respective component spectra of the active site and the unprecedented proximal
      [4Fe-3S] cluster using a combination of statistical methods and global fitting
      procedures. These component spectra of the individual cofactors were compared
      with calculated spectra obtained by quantum mechanics/molecular mechanics (QM/MM)
      methods. Thus, the recently discovered hydroxyl-coordination of one iron in the
      [4Fe-3S] cluster was confirmed. Infrared (IR) microscopy of oxidized MBH crystals
      revealed the [NiFe] active site to be in the Nir-B [Ni(III)] and Nir-S [Ni(II)]
      states, whereas RR measurements of these crystals uncovered the Nia-S [Ni(II)]
      state as the main spectral component, suggesting its in situ formation via
      photodissociation of the assumed bridging hydroxyl or water ligand. On the basis
      of QM/MM calculations, individual band frequencies could be correlated with
      structural parameters for the Nia-S state as well as for the Ni-L state, which is
      formed upon photodissociation of the bridging hydride of H2-reduced active site
      states. 

PMID- 26201815
TI  - The Charta of Vicenza.

PMID- 26201816
TI  - Best (but oft-forgotten) practices: checking assumptions concerning regression
      residuals.
AB  - The residuals of a least squares regression model are defined as the observations
      minus the modeled values. For least squares regression to produce valid CIs and P
      values, the residuals must be independent, be normally distributed, and have a
      constant variance. If these assumptions are not satisfied, estimates can be
      biased and power can be reduced. However, there are ways to assess these
      assumptions and steps one can take if the assumptions are violated. Here, we
      discuss both assessment and appropriate responses to violation of assumptions. 

PMID- 26201817
TI  - Pyridoxine supplementation does not alter in vivo kinetics of one-carbon
      metabolism but modifies patterns of one-carbon and tryptophan metabolites in
      vitamin B-6-insufficient oral contraceptive users.
AB  - BACKGROUND: Low chronic vitamin B-6 status can occur in a subset of women who use
      oral contraceptives (OCs) with uncertain metabolic consequences. An insufficiency
      of cellular pyridoxal 5'-phosphate (PLP), which is the coenzyme form of vitamin B
      6, may impair many metabolic processes including one-carbon and tryptophan
      metabolism. OBJECTIVE: We investigated the effects of vitamin B-6 supplementation
      on the in vivo kinetics of one-carbon metabolism and the concentration of one
      carbon and tryptophan metabolites in vitamin B-6-deficient OC users. DESIGN: A
      primed, constant infusion of [(13)C5]methionine, [3-(13)C]serine, and
      [(2)H3]leucine was performed on 10 OC users (20-40 y old; plasma PLP
      concentrations <30 nmol/L) before and after 28 d of supplementation with 10 mg
      pyridoxine hydrochloric acid/d. In vivo fluxes of total homocysteine
      remethylation, the remethylation of homocysteine from serine, and rates of
      homocysteine and cystathionine production were assessed. Targeted metabolite
      profiling was performed, and data were analyzed by using orthogonal partial least
      squares-discriminant analysis and paired t tests adjusted for multiple testing.
      RESULTS: Pyridoxine supplementation increased the mean +/- SD plasma PLP
      concentration from 25.8 +/- 3.6 to 143 +/- 58 nmol/L (P < 0.001) and decreased
      the leucine concentration from 103 +/- 17 to 90 +/- 20 nmol/L (P = 0.007) and
      glycine concentration from 317 +/- 63 to 267 +/- 58 nmol/L (P = 0.03).
      Supplementation did not affect in vivo rates of homocysteine remethylation or the
      appearance of homocysteine and cystathionine. A multivariate analysis showed a
      clear overall effect on metabolite profiles resulting from supplementation.
      Leucine, glycine, choline, cysteine, glutathione, trimethylamine N-oxide, and the
      ratios glycine:serine, 3-hydroxykynurenine:kynurenine, 3-hydroxykynurenine:3
      hydroxyanthranilic acid, and 3-hydroxykynurenine:anthranilic acid were
      significant discriminating variables. CONCLUSIONS: Consistent with previous
      vitamin B-6-restriction studies, fluxes of one-carbon metabolic processes
      exhibited little or no change after supplementation in low-vitamin B-6 subjects.
      In contrast, changes in the metabolic profiles after supplementation indicated
      perturbations in metabolism, suggesting functional vitamin B-6 deficiency. This
      study was registered at clinicaltrials.gov as NCT01128244.

PMID- 26201818
TI  - Sleeve gastrectomy effects on hunger, satiation, and gastrointestinal hormone and
      motility responses after a liquid meal test.
AB  - BACKGROUND: The relation between hunger, satiation, and integrated
      gastrointestinal motility and hormonal responses in morbidly obese patients after
      sleeve gastrectomy has not been determined. OBJECTIVE: The objective was to
      assess the effects of sleeve gastrectomy on hunger, satiation, gastric and
      gallbladder motility, and gastrointestinal hormone response after a liquid meal
      test. DESIGN: Three groups were studied: morbidly obese patients (n = 16),
      morbidly obese patients who had had sleeve gastrectomy (n = 8), and nonobese
      patients (n = 16). The participants fasted for 10 h and then consumed a 200-mL
      liquid meal (400 kcal + 1.5 g paracetamol). Fasting and postprandial hunger,
      satiation, hormone concentrations, and gastric and gallbladder emptying were
      measured several times over 4 h. RESULTS: No differences were observed in hunger
      and satiation curves between morbidly obese and nonobese groups; however, sleeve
      gastrectomy patients were less hungry and more satiated than the other groups.
      Antrum area during fasting in morbidly obese patients was statistically
      significant larger than in the nonobese and sleeve gastrectomy groups. Gastric
      emptying was accelerated in the sleeve gastrectomy group compared with the other
      2 groups (which had very similar results). Gallbladder emptying was similar in
      the 3 groups. Sleeve gastrectomy patients showed the lowest ghrelin
      concentrations and higher early postprandial cholecystokinin and glucagon-like
      peptide 1 peaks than did the other participants. This group also showed an
      improved insulin resistance pattern compared with morbidly obese patients.
      CONCLUSIONS: Sleeve gastrectomy seems to be associated with profound changes in
      gastrointestinal physiology that contribute to reducing hunger and increasing
      sensations of satiation. These changes include accelerated gastric emptying,
      enhanced postprandial cholecystokinin and glucagon-like peptide 1 concentrations,
      and reduced ghrelin release, which together may help patients lose weight and
      improve their glucose metabolism after surgery. This trial was registered at
      clinicaltrials.gov as NCT02414893.

PMID- 26201819
TI  - The Arabidopsis information resource: Making and mining the "gold standard"
      annotated reference plant genome.
AB  - The Arabidopsis Information Resource (TAIR) is a continuously updated, online
      database of genetic and molecular biology data for the model plant Arabidopsis
      thaliana that provides a global research community with centralized access to
      data for over 30,000 Arabidopsis genes. TAIR's biocurators systematically
      extract, organize, and interconnect experimental data from the literature along
      with computational predictions, community submissions, and high throughput
      datasets to present a high quality and comprehensive picture of Arabidopsis gene
      function. TAIR provides tools for data visualization and analysis, and enables
      ordering of seed and DNA stocks, protein chips, and other experimental resources.
      TAIR actively engages with its users who contribute expertise and data that
      augments the work of the curatorial staff. TAIR's focus in an extensive and
      evolving ecosystem of online resources for plant biology is on the critically
      important role of extracting experimentally based research findings from the
      literature and making that information computationally accessible. In response to
      the loss of government grant funding, the TAIR team founded a nonprofit entity,
      Phoenix Bioinformatics, with the aim of developing sustainable funding models for
      biological databases, using TAIR as a test case. Phoenix has successfully
      transitioned TAIR to subscription-based funding while still keeping its data
      relatively open and accessible.

PMID- 26201821
TI  - JPEN Journal Club 14. Relative vs Absolute Efficacy.

PMID- 26201820
TI  - Fetal and infant exposure to the Chinese famine increases the risk of fatty liver
      disease in Chongqing, China.
AB  - BACKGROUND AND AIM: Early life exposure to the famine may affect the
      susceptibility to the metabolic disorders. The objective of this study was to
      examine the associations of early life exposure to the Chinese Famine (1959-1961)
      with the risk of fatty liver disease, obesity, hypertension, and hyperglycemia in
      adulthood. METHODS: We used the data of 10,935 adults born between 1956 and 1965
      in Chongqing from check-up center at the 1st Affiliated Hospital of Chongqing
      Medical University in 2011. Logistic regression models were used to explore the
      effects of famine on the risk of fatty liver disease, obesity, hypertension, and
      hyperglycemia. RESULTS: In Chongqing, prevalences of fatty liver disease among
      adults in non-exposed (1956-1958 plus 1963-1965) group and born in 1959, 1960,
      1961, and 1962 were 34.01%, 36.42%, 34.63%, 40.27%, and 36.09%, respectively.
      Prevalences of fatty liver disease, obesity, hypertension, and hyperglycemia were
      significantly higher in males versus females. The risk of fatty liver disease was
      about 1.375-fold (1.303 (95% confidence interval, 1.066-1.594) for male,
      1.547(95% confidence interval, 1.195-2.002) for female) higher in subjects born
      in 1961, and 1.142-fold (1.117 (95% confidence interval, 0.957-1.305) for male,
      1.242 (95% confidence interval, 1.003-1.537) for female) higher in subjects born
      in 1962 after adjustment of age and sex, compared with non-exposed subjects.
      Early life exposure to the Chinese famine was also associated with the increased
      risk of obesity and hyperglycemia. CONCLUSIONS: Exposure to the Chinese famine
      during fetal life and infancy was associated with an increased risk of fatty
      liver disease in adulthood.

PMID- 26201822
TI  - Should preoperative chest computed tomography be performed in all patients with
      colorectal cancer?
AB  - AIM: This study evaluated the accuracy of chest computed tomography (CCT) in the
      preoperative staging of patients with potentially resectable colorectal cancer
      (CRC). An attempt was made to determine whether CCT has a significant influence
      on management and clinical outcome. METHOD: A review was conducted of all
      preoperative CCTs and X-rays performed in patients submitted to elective
      resection of CRC at our institution between 2005 and 2012. All scans were revised
      by an independent radiologist who was unaware of the circumstances of each case.
      The findings were classified as benign, malignant or indeterminate. Patients were
      followed for at least 12 months after surgery to assess the clinical evolution of
      any lesion found on CCT and the oncological outcome. RESULTS: Two hundred and
      twenty-three patients were included. The CCT showed normal or benign findings in
      157 (70.4%) patients, a malignant lesion in 17 (7.6%), and an indeterminate lung
      lesion (ILL) in 49 (22%). Of the 30 patients with proven lung metastases, a plain
      X-ray detected lesions in only 11 (36.7%) patients. During the postoperative
      follow-up, 14 (28.6%) of the 49 patients with ILL demonstrated malignant
      progression of the lung lesions. Among all 223 patients, only six (2.7%)
      underwent lung resection. CONCLUSION: CCT is superior to plain X-ray for the
      detection of lung metastases. Despite the medical and financial implications of
      preoperative CCT, only a small number of patients will eventually undergo lung
      resection. We call into question the role of routine CCT in the staging of
      patients with CRC. A more selective approach, reserving CT for patients at high
      risk of lung metastases, is suggested.

PMID- 26201823
TI  - Findings in pancreatic MRI associated with pancreatic fibrosis and HbA1c values.
AB  - PURPOSE: To evaluate the diagnostic performance of noncontrast-enhanced magnetic
      resonance imaging (MRI) to grade pancreatic fibrosis and to assess hemoglobin
      (Hb) A1c values. MATERIALS AND METHODS: Twenty-nine consecutive patients with
      pancreatic or biliary malignancy who underwent pancreatectomy were evaluated.
      Patients were classified into three groups: HbA1c < 5.7 (group 1), 5.7 <= HbA1c <
      6.5 (group 2), and HbA1c >= 6.5 (group 3). MRI of the pancreas was performed
      using a 1.5T MR system. The pancreas-to-muscle signal intensity ratio (SIR) on in
      and opposed-phase T1 -, T2 -, and diffusion-weighted images, as well as the
      apparent diffusion coefficient were calculated. MRI measurements, degrees of
      pancreatic fibrosis, and HbA1c values were compared using multiple regression
      analysis and Kruskal-Wallis test. RESULTS: The pancreatic fibrosis grade was
      negatively correlated with the SIR on in-phase T1 -weighted images (r = -0.67, P
      = 0.0002). The pancreatic fibrosis grade and HbA1c value were negatively
      correlated with the SIR on opposed-phase T1 -weighted images (r = -0.47, P =
      0.019 and r = -0.51, P = 0.0089, respectively). SIRs on in- and opposed-phase T1 
      weighted images were significantly lower in group 3 than in groups 1 and 2 (P <
      0.05). CONCLUSION: The pancreas-to-muscle SIRs on in- and opposed-phase T1 
      weighted images could be a potential biomarker for pancreatic fibrosis and
      elevated HbA1c values.

PMID- 26201824
TI  - Standardization of FT4 and harmonization of TSH measurements - a request for
      input from endocrinologists and other physicians.

PMID- 26201826
TI  - Sexual information needs of Arab-Muslim patients with cardiac problems.
AB  - Cardiac diseases have direct and indirect effects on sexuality. Health care
      providers, especially nurses, have a major responsibility in addressing and
      discussing sexual concerns and providing sexual counseling needs for patients
      with cardiac diseases. Discussing sexual issues in Arabic Muslim countries is
      considered a taboo. Lack of information about sexual life can affect the quality
      of life for patients with cardiac diseases. In this study, concerns regarding
      counseling needs and sexual information pertaining to Jordanian patients with
      cardiac diseases are addressed. Non-experimental, cross-sectional, descriptive
      designs were employed, accompanied by a self-report questionnaire, as well as a
      structured interview using the Steinke Sexual Concerns and Sexual Activity
      questionnaires for cardiac patients. A convenient sample of Jordanian male and
      female patients with cardiac problems was recruited. Results revealed that only
      11% of the participants with cardiac diseases reported receiving information
      regarding sexual life following cardiac-related events. Most patients (71%, F=81)
      preferred cardiologists to provide them with sexual information, and almost two
      thirds of them (62%, F=75) considered nurses' gender to be a barrier, preventing
      them from inquiring about their sexual life. Patients with cardiac diseases had
      sexual concerns, but none of incredible importance. However, most patients (76%,
      F=94) reported changes in sexual activities following cardiac-related events.
      Cardiac patients had sexual concerns and sexual counseling needs that they would
      not discuss. Health care professionals should arrange sexual counseling plans
      with the patient; as every patient has individual, specific, and unique sexual
      counseling needs, dependent upon their lifestyle, health conditions, and their
      type of cardiac disease. 

PMID- 26201827
TI  - Carbon hybridized halloysite nanotubes for high-performance hydrogen storage
      capacities.
AB  - Hybrid nanotubes of carbon and halloysite nanotubes (HNTs) with different
      carbon:HNTs ratio were hydrothermally synthesized from natural halloysite and
      sucrose. The samples display uniformly cylindrical hollow tubular structure with
      different morphologies. These hybrid nanotubes were concluded to be promising
      medium for physisorption-based hydrogen storage. The hydrogen adsorption capacity
      of pristine HNTs was 0.35% at 2.65 MPa and 298 K, while that of carbon coated
      HNTs with the pre-set carbon:HNTs ratio of 3:1 (3C-HNTs) was 0.48% under the same
      condition. This carbon coated method could offer a new pattern for increasing the
      hydrogen adsorption capacity. It was also possible to enhance the hydrogen
      adsorption capacity through the spillover mechanism by incorporating palladium
      (Pd) in the samples of HNTs (Pd-HNTs) and 3C-HNTs (Pd-3C-HNTs and 3C-Pd-HNTs are
      the samples with different location of Pd nanoparticles). The hydrogen adsorption
      capacity of the Pd-HNTs was 0.50% at 2.65 MPa and 298 K, while those of Pd-3C
      HNTs and 3C-Pd-HNTs were 0.58% and 0.63%, respectively. In particular, for this
      spillover mechanism of Pd-carbon-HNTs ternary system, the bidirectional
      transmission of atomic and molecular hydrogen (3C-Pd-HNTs) was concluded to be
      more effective than the unidirectional transmission (Pd-3C-HNTs) in this work for
      the first time. 

PMID- 26201825
TI  - (18)F-NaF PET/CT: EANM procedure guidelines for bone imaging.
AB  - The aim of this guideline is to provide minimum standards for the performance and
      interpretation of (18)F-NaF PET/CT scans. Standard acquisition and interpretation
      of nuclear imaging modalities will help to provide consistent data acquisition
      and numeric values between different platforms and institutes and to promote the
      use of PET/CT modality as an established diagnostic modality in routine clinical
      practice. This will also improve the value of scientific work and its
      contribution to evidence-based medicine.

PMID- 26201829
TI  - Could the organ shortage ever be met?
AB  - The organ shortage is commonly presented as having a clear solution, increase the
      number of organs donated and the problem will be solved. In the light of the
      Northern Ireland Assembly's consultation on moving to an opt-out organ donor
      register this article focuses on the social factors and complexities which impact
      strongly on both the supply of, and demand for, transplantable organs. Judging by
      the experience of other countries presumed consent systems may or may not
      increase donations but have not met demand. Donation rates have risen
      considerably in all parts of the UK recently but there is also an increasing
      demand for organs. Looking at international donation rates and attitudes, future
      demand for organs and education on donation, the question is whether the organ
      shortage could ever be met. The increase in longevity, in rates of diabetes and
      obesity and in alcohol related liver disease all contribute both to increased
      demand for transplants, and re-transplants, and a reduction in the number of
      usable organs. It is unlikely that demand could ever be met, since, if supply was
      unlimited, the focus would move to financial resources and competing demands on
      the health care budget in a publicly funded health system. These factors point to
      the need to focus on ways of reducing, or at least stabilizing, demand where
      lifestyle factors contribute to the underlying disease.

PMID- 26201831
TI  - Sperm DNA fragmentation abnormalities in men from couples with a history of
      recurrent miscarriage.
AB  - BACKGROUND: Previous studies have described an association between sperm with DNA
      damage and a history of recurrent miscarriage (RM), although it is not clear
      whether there is benefit in screening for sperm DNA fragmentation and to what
      extent DNA fragmentation impacts upon RM. AIMS: To identify what proportion of
      couples experiencing RM are affected by DNA fragmentation abnormalities.
      MATERIALS AND METHODS: In this retrospective study, between 2008 and 2013,
      couples with a history of recurrent miscarriage (>=3 first trimester
      miscarriages) were investigated comprehensively for known causes (karyotype,
      uterine, antiphospholipid syndrome, thrombophilia) and also by semen analysis,
      including DNA fragmentation [sperm chromatin structure analysis (SCSA)].
      Statistical analysis was performed on SPSS software with significance taken as P
      < 0.05. RESULTS: There were 108 couples with a median sperm DNA fragmentation
      index (DFI) of 9.50%. Normal levels were found in 70.5% of men (DFI < 15%), 23%
      had high levels (DFI 15-30%), and 6.5% had very high levels (DFI > 30%). Couples
      with otherwise unexplained recurrent miscarriage had significantly higher DFI
      than those with other causes identified on routine screening (P = 0.012).
      CONCLUSIONS: In couples experiencing RM, 30% (32/108) of men had sperm with high
      levels of DNA fragmentation (DFI > 15%). This may be a contributing factor to the
      clinical syndrome of RM, and future clinical trials of therapies for these
      couples are warranted.

PMID- 26201830
TI  - Low-Intensity Pulsed Ultrasound Improves the Functional Properties of Cardiac
      Mesoangioblasts.
AB  - Cell-based therapy is a promising approach for many diseases, including ischemic
      heart disease. Cardiac mesoangioblasts are committed vessel-associated
      progenitors that can restore to a significant, although partial, extent, heart
      structure and function in a murine model of myocardial infarction. Low-intensity
      pulsed ultrasound (LIPUS) is a non-invasive form of mechanical energy that can be
      delivered into biological tissues as acoustic pressure waves, and is widely used
      for clinical applications including bone fracture healing. We hypothesized that
      the positive effects of LIPUS on bone and soft tissue, such as increased cell
      differentiation and cytoskeleton reorganization, could be applied to increase the
      therapeutic potential of mesoangioblasts for heart repair. In this work, we show
      that LIPUS stimulation of cardiac mesoangioblasts isolated from mouse and human
      heart results in significant cellular modifications that provide beneficial
      effects to the cells, including increased malleability and improved motility.
      Additionally, LIPUS stimulation increased the number of binucleated cells and
      induced cardiac differentiation to an extent comparable with 5'-azacytidine
      treatment. Mechanistically, LIPUS stimulation activated the BMP-Smad signalling
      pathway and increased the expression of myosin light chain-2 together with
      upregulation of beta1 integrin and RhoA, highlighting a potentially important
      role for cytoskeleton reorganization. Taken together, these results provide
      functional evidence that LIPUS might be a useful tool to explore in the field of
      heart cell therapy.

PMID- 26201832
TI  - Endoplasmic Reticulum Stress Interacts With Inflammation in Human Diseases.
AB  - The endoplasmic reticulum (ER) is a critical organelle for normal cell function
      and homeostasis. Disturbance in the protein folding process in the ER, termed ER
      stress, leads to the activation of unfolded protein response (UPR) that
      encompasses a complex network of intracellular signaling pathways. The UPR can
      either restore ER homeostasis or activate pro-apoptotic pathways depending on the
      type of insults, intensity and duration of the stress, and cell types. ER stress
      and the UPR have recently been linked to inflammation in a variety of human
      pathologies including autoimmune, infectious, neurodegenerative, and metabolic
      disorders. In the cell, ER stress and inflammatory signaling share extensive
      regulators and effectors in a broad spectrum of biological processes. In spite of
      different etiologies, the two signaling pathways have been shown to form a
      vicious cycle in exacerbating cellular dysfunction and causing apoptosis in many
      cells and tissues. However, the interaction between ER stress and inflammation in
      many of these diseases remains poorly understood. Further understanding of the
      biochemistry, cell biology, and physiology may enable the development of novel
      therapies that spontaneously target these pathogenic pathways.

PMID- 26201833
TI  - Inflight Emergencies During Eurasian Flights.
AB  - BACKGROUND: This study evaluated the incidence and status of urgent medical
      conditions, the attitudes of health professionals who encounter such conditions,
      the adequacy of medical kits and training of cabin crew in data-received-company
      aircrafts suggested by Aerospace Medical Association, and the demographic data of
      patients. METHODS: Data were collected from medical records of a major flight
      company from 2011 through 2013. All patients with complete records were included
      in the study. Numerical variables were defined as median and interquartiles (IQR)
      for median, while categorical variables were defined as numbers and percentage.
      RESULTS: During the study period, 10,100,000 passengers were carried by the
      company flights, with 1,312 (0.013%) demands for urgent medical support (UMS).
      The median age of the passengers who requested UMS was 45 years (IQR: 29-62).
      Females constituted 698 (53.2%) among the patients, and 721 (55%) patients were
      evaluated by medical professionals found among passengers. The most common
      nontraumatic complaints resulting in requests for UMS were flight anxiety (311
      patients, 23.7%) and dyspnea (145 patients, 11%). The most common traumatic
      complaint was burns (221 patients, 16.8%) resulting from trauma during flight. A
      total of 22 (1.67%) emergency landings occurred for which the most frequent
      reasons were epilepsy (22.7%) and death (18.2%). Deaths during flights were
      recorded in 13 patients, whose median age was 77 years (IQR: 69-82), which was
      significantly higher compared to the age of patients requiring UMS (p < 0.0001).
      A total of 592 (45%) patients did not require any treatment for UMS. Medical kits
      and training were found to be sufficient according to the symptomatic treatments.
      CONCLUSION: Most of the urgent cases encountered during flights can be
      facilitated with basic medical support. "Traumatic emergency procedures inflight
      medical care" would be useful for additional training. Medical professionals as
      passengers are significantly involved in encountered emergency situations. Adding
      automated external defibrillator and pulse oximetry to recommended kits and
      training can help facilitate staff decisions such as emergency landings and tele
      assistance.

PMID- 26201834
TI  - Increased Cytotoxicity of Vanadium to CHO-K1 Cells in the Presence of Inorganic
      Selenium.
AB  - The effect of selenium applied as sodium selenite (Na2SeO3) on the cytotoxicity
      of vanadyl sulphate (VOSO4) was examined using CHO-K1 cells. From the resazurin
      based assay, it appears that Na2SeO3 at low doses (0.5 and 1 MUM) can enhance 100
      MUM VOSO4-induced cell damage. The two-way ANOVA analysis revealed that the
      increased cell damage was a consequence of a synergistic interaction of 0.5 MUM
      Na2SeO3 with VOSO4 and 1 MUM Na2SeO3 with VOSO4. Observations performed with a
      phase-contrast microscope showed most cells to be rounded upon treatment with
      VOSO4 alone. In turn, a majority of cells co-treated with VOSO4 and 1 MUM Na2SeO3
      were elongated, and exhibited cytoplasmic vacuolization. These results warn of
      the potential contribution of inorganic selenium to vanadium-induced toxicity. 

PMID- 26201835
TI  - Randomized, placebo-controlled trial of incobotulinumtoxina for upper-limb post
      stroke spasticity.
AB  - INTRODUCTION: Efficacy and safety of incobotulinumtoxinA in post-stroke upper
      limb spasticity were studied. METHODS: Subjects randomized 2:1 to
      incobotulinumtoxinA (fixed dose 400 U) or placebo, with fixed doses for the
      primary target clinical pattern (PTCP; flexed elbow, 200 U; flexed wrist, 150 U;
      clenched fist, 100 U). Doses for non-primary patterns were flexible within
      predefined ranges. RESULTS: At week 4, incobotulinumtoxinA led to larger
      improvements in PTCP Ashworth scale (AS) scores than placebo [least-squares mean
      change +/- standard error: -0.9 +/- 0.06 (n = 171) vs. -0.5 +/- 0.08 (n = 88); P
      < 0.001], and more subjects were PTCP AS responders (>=1-point improvement) with
      incobotulinumtoxinA (69.6%) than with placebo (37.5%; P < 0.001). Investigator's
      Global Impression of Change confirmed superiority of incobotulinumtoxinA vs.
      placebo (P = 0.003). IncobotulinumtoxinA was associated with functional
      improvements, as demonstrated in responder rates for Disability Assessment Scale
      principal target at week 4 (P = 0.007). Adverse events were mainly mild/moderate,
      and were reported by 22.4% (incobotulinumtoxinA) and 16.8% (placebo) of subjects.
      CONCLUSIONS: IncobotulinumtoxinA significantly improved upper-limb spasticity and
      associated disability, and was well-tolerated.

PMID- 26201836
TI  - Subcellular Distribution of NTL Transcription Factors in Arabidopsis thaliana.
AB  - NAC with a transmembrane (TM) motif1-like (NTL) transcription factors, containing
      three regions: the N-terminal NAC domain (ND), the middle regulation region (RR),
      and the C-terminal TM domain, belong to the tail-anchored proteins. Although
      these NTLs play numerous essential roles in plants, their subcellular
      distribution and the mechanism of translocation into the nucleus (NU) remain
      unclear. In this study, we found that most of the full-length NTLs were localized
      in the endoplasmic reticulum (ER), with the exception of NTL11 and NTL5, which
      were restricted to the NU. Furthermore, we found that NTL11 contains a TM domain,
      whereas NTL5 does not. The ND of all of the NTLs was responsible for nuclear
      localization in plants. After truncation of the TM domain, NTL8_NR, NTL10_NR and
      NTL13_NR localized in the cytoplasm (CT) and NU, and other NTL_NRs were only
      localized in the NU, suggesting that the RR of NTL8, NTL10 and NTL13 contains
      some inhibitory region to mask the nuclear localization signal sequence in the ND
      domain and permit their diffusion between CT and NU. Furthermore, the N-terminus
      of NTL11 was translocated to the NU, but the C-terminus was degraded in
      Arabidopsis mesophyll protoplasts. The chimeric construct of NTL11_ND with
      NTL10_RR and TM domain (11ND-10RT) was localized exclusively in the ER, and not
      in the NU. However, 10ND-11RT was found mainly in the NU. Our results indicated
      that the TM domain is essential for NTL targeting the ER and the N-terminal
      fragment, including ND and RR, is translocated into the NU after activation
      through proteolytic cleavage events upon stimulation by internal and external
      environmental signals. 

PMID- 26201837
TI  - Metaproteomics of activated sludge from a wastewater treatment plant - a pilot
      study.
AB  - In this study, the impact of protein fractionation techniques prior to LC/MS
      analysis was investigated on activated sludge samples derived at winter and
      summer condition from a full-scale wastewater treatment plant (WWTP). For
      reduction of the sample complexity, different fractionation techniques including
      RP-LC (1D-approach), SDS-PAGE and RP-LC (2D-approach) as well as RP-LC, SDS-PAGE
      and liquid IEF (3D-approach) were carried out before subsequent ion trap MS
      analysis. The derived spectra were identified by MASCOT search using a
      combination of the public UniProtKB/Swiss-Prot protein database and metagenome
      data from a WWTP. The results showed a significant increase of identified
      spectra, enabled by applying IEF and SDS-PAGE to the proteomic workflow. Based on
      meta-proteins, a core metaproteome and a corresponding taxonomic profile of the
      wastewater activated sludge were described. Functional aspects were analyzed
      using the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway library by
      plotting KEGG Orthology identifiers (KO numbers) of protein hits into pathway
      maps of the central carbon (map01200) and nitrogen metabolism (map00910). Using
      the 3D-approach, most proteins involved in glycolysis and citrate cycle and
      nearly all proteins of the nitrogen removal were identified, qualifying this
      approach as most promising for future studies. All MS data have been deposited in
      the ProteomeXchange with identifier PXD001547
      (http://proteomecentral.proteomexchange.org/dataset/PXD001547). 

PMID- 26201838
TI  - The clinical anatomy of accessory mental nerves and foramina.
AB  - Since three-dimensional computed tomography was developed, many researchers have
      described accessory mental foramina. The anatomical and radiological findings
      have been discussed, but details of accessory mental nerves (AMNs) have only been
      researched in a small number of anatomical and clinical cases. For this article,
      we reviewed the literature relating to accessory mental foramina (AMFs) and
      nerves to clarify aspects important for clinical situations. The review showed
      that the distribution pattern of the AMN can differ according to the position of
      the accessory mental foramen, and the reported incidence of AMFs differs among
      observation methods. A review of clinical cases also revealed that injury to
      large AMF can result in paresthesia. This investigation did not reveal all
      aspects of AMNs and AMFs, but will be useful for diagnosis and treatment by many
      dentists and oral and maxillofacial surgeons.

PMID- 26201839
TI  - The Role of Metabolomics in Brain Metabolism Research.
AB  - This special edition of the Journal of Neuroimmune Pharmacology focuses on the
      leading edge of metabolomics in brain metabolism research. The topics covered
      include a metabolomic field overview and the challenges in neuroscience
      metabolomics. The workflow and utility of different analytical platforms to
      profile complex biological matrices that include biofluids, brain tissue and
      cells, are shown in several case studies. These studies demonstrate how global
      and targeted metabolite profiling can be applied to distinguish disease stages
      and to understand the effects of drug action on the central nervous system (CNS).
      Finally, we discuss the importance of metabolomics to advance the understanding
      of brain function that includes ligand-receptor interactions and new insights
      into the mechanisms of CNS disorders. 

PMID- 26201840
TI  - Antisense- and siRNA-mediated inhibition of the anti-apoptotic gene Bcl-xL for
      chemosensitization of bladder cancer cells.
AB  - Bcl-xL is an apoptosis inhibitor that is upregulated in bladder cancer (BCa) and
      provides an attractive target for molecular therapies. Treatment with specific
      antisense oligodeoxynucleotides (AS-ODNs) or small interfering RNAs (siRNAs) were
      able to sensitize BCa cells to conventional chemotherapeutics. Ten new Bcl-xL
      targeting AS-ODNs were systematically designed by using predicting software. AS
      BX2034 and AS-BX2100 as well as the previously optimized siRNA construct si-BX713
      were selected for further detailed in vitro analysis in the BCa cell lines UM-UC
      3 and EJ28. Bcl-xL mRNA and protein expression levels, cell viability and
      apoptosis were examined 72 h after transfection. A single treatment with AS
      BX2034 or AS-BX2100 caused only a low inhibition of the Bcl-xL mRNA expression
      with the highest reduction of <=20% in UM-UC-3 cells. In contrast, a single
      treatment with si-BX713 strongly decreased Bcl-xL mRNA expression level by <=69%
      in UM-UC-3 cells and by <=86% in EJ28 cells. Both gene expression inhibitor types
      induced a low to moderate reduction of viability. Depending on the cell line, a
      combined treatment with AS-BX2100 or si-BX713 and cisplatin (CDDP) caused an
      additional inhibition of cell viability by ~33 and 38%, respectively, compared to
      the respective control construct combined with CDDP. In comparison to the
      respective control treatment, combinations of AS-BX2100 and CDDP led to a
      stronger induction of apoptosis by 57% in UM-UC-3 cells and 44% in EJ28 cells,
      whereas the combination of si-BX713 and CDDP enhanced apoptosis by 38 and 118% in
      UM-UC-3 and EJ28 cells, respectively. Our comparative studies showed a stronger
      knockdown of Bcl-xL by the siRNA construct compared to AS-ODN treatment in both
      BCa cell lines. In combinatory treatments, the Bcl-xL-directed siRNA markedly
      enhanced the anti-proliferative and apoptotic effects of CDDP and therefore, may
      serve as suitable tool for chemosensitization of BCa cells. 

PMID- 26201841
TI  - Ethical dilemmas with the use of ECMO as a bridge to transplantation.

PMID- 26201842
TI  - Evaluation of extracellular matrix protein CCN1 as a prognostic factor for
      glioblastoma.
AB  - Recently, research efforts in identifying prognostic molecular biomarkers for
      malignant glioma have intensified. Cysteine-rich protein 61 (CCN1) is one of the
      CCN family of matricellular proteins that promotes cell growth and angiogenesis
      in cancers through its interaction with several integrins. In this study, we
      investigated the relationships among CCN1, O(6)-methylguanine-DNA
      methyltransferase expression, the tumor removal rate, and prognosis in 46
      glioblastoma patients treated at the Okayama University Hospital. CCN1 expression
      was high in 31 (67 %) of these patients. The median progression-free survival
      (PFS) and overall survival (OS) times of patients with high CCN1 expression was
      significantly shorter than those of patients with low CCN1 expression (p <
      0.005). In a multivariate Cox analysis, CCN1 proved to be an independent
      prognostic factor for patient survival [PFS, hazard ratio (HR) = 3.53 (1.55
      8.01), p = 0.003 and OS, HR = 3.05 (1.35-6.87), p = 0.007]. Moreover, in the 31
      patients who underwent gross total resection, the PFS and OS times of those with
      high CCN1 expression were significantly shorter than those with low CCN1
      expression. It was concluded that CCN1 might emerge as a significant prognostic
      factor regarding the prognosis of glioblastoma patients. 

PMID- 26201843
TI  - Running with neighbors: coordinating cell migration and cell-cell adhesion.
AB  - Coordinated movement of large groups of cells is required for many biological
      processes, such as gastrulation and wound healing. During collective cell
      migration, cell-cell and cell-extracellular matrix (ECM) adhesions must be
      integrated so that cells maintain strong interactions with neighboring cells and
      the underlying substratum. Initiation and maintenance of cadherin adhesions at
      cell-cell junctions and integrin-based cell-ECM adhesions require integration of
      mechanical cues, dynamic regulation of the actin cytoskeleton, and input from
      specific signaling cascades, including Rho family GTPases. Here, we summarize
      recent advances made in understanding the interplay between these pathways at
      cadherin-based and integrin-based adhesions during collective cell migration and
      highlight outstanding questions that remain in the field. 

PMID- 26201844
TI  - BMP-2, PDGF-BB, and bone marrow mesenchymal cells in a macroporous beta-TCP
      scaffold for critical-size bone defect repair in rats.
AB  - The aim of this work was to study the bone repair induced by bone morphogenetic
      protein-2 (BMP-2), rat mesenchymal stem cells (rMSCs), and platelet-derived
      growth factor (PDGF-BB) incorporated in a macroporous beta-tricalcium phosphate
      (beta-TCP) system fabricated by robocasting, and to identify the most beneficial
      combination in a critical rat calvaria defect. BMP-2 was formulated in
      microspheres to provide a prolonged, local concentration, whereas PDGF-BB, which
      acts during the initial stage of defect repair, was incorporated in a thin layer
      of crosslinked alginate. Approximately 80% of PDGF-BB and 90% of BMP-2 were
      released into the defect during the first 2 d and 3 weeks, respectively.
      Histological analyses indicated a minor synergistic effect in the BMP-2-MSC
      groups. In contrast, significant antagonism was found with combined BMP-2 and
      PDGF-BB defect treatment. The high-grade repair induced by BMP-2 rules out any
      advantage from combining BMP-2 with PDGF-BB or MSCs, at least with this scaffold
      and defect model. 

PMID- 26201845
TI  - Mixing of components from different manufacturers in total hip arthroplasty:
      prevalence and comparative outcomes.
AB  - BACKGROUND AND PURPOSE: There have recently been highly publicized examples of
      suboptimal outcomes with some newer implant designs used for total hip
      replacement. This has led to calls for tighter regulation. However, surgeons do
      not always adhere to the regulations already in place and often use implants from
      different manufacturers together to replace a hip, which is against the
      recommendations of the Medicines and Healthcare Products Regulatory Agency (MHRA)
      and the directions of the manufacturers. PATIENTS AND METHODS: We used data from
      the National Joint Registry of England and Wales (NJR) to investigate this
      practice. RESULTS: Mixing of components was common, and we identified over 90,000
      cases recorded between 2003 and 2013. In the majority of these cases (48,156),
      stems and heads from one manufacturer were mixed with polyethylene cemented cups
      from another manufacturer. When using a cemented stem and a polyethylene cup,
      mixing of stems from one manufacturer with cups from another was associated with
      a lower revision rate. At 8 years, the cumulative percentage of revisions was
      1.9% (95% CI: 1.7-2.1) in the mixed group as compared to 2.4% (2.3-2.5) in the
      matched group (p = 0.001). Mixing of heads from one manufacturer with stems from
      another was associated with a higher revision rate (p < 0.001). In hip
      replacements with ceramic-on-ceramic or metal-on-metal bearings, mixing of stems,
      heads, and cups from different manufacturers was associated with similar revision
      rates (p > 0.05). INTERPRETATION: Mixing of components from different
      manufacturers is a common practice, despite the fact that it goes against
      regulatory guidance. However, it is not associated with increased revision rates
      unless heads and stems from different manufacturers are used together.

PMID- 26201846
TI  - Long-Term Functional, Cosmetic and Sexual Outcomes of Hypospadias Correction
      Performed in Childhood.
AB  - OBJECTIVE: Hypospadias surgery, especially when performed early in life, may have
      a significant impact on the urinary and sexual functions in an adult. Because the
      literature is still limited, this paper assesses long-term functional, cosmetic
      and sexual results of hypospadias repair performed in childhood. PATIENTS AND
      METHODS: The study includes 275 patients older than 12 years treated for a
      hypospadias by an Onlay, Mathieu, Duplay, or Duckett's technique between January
      1990 and December 2000. Flowmetry results were retrospectively obtained from
      patients' charts. The Paediatric Penile Perception Score (PPPS), the Hypospadias
      Objective Scoring Evaluation (HOSE) and the IIEF-5 score (when older than 16
      years old) questionnaires were used to assess cosmetic and sexual results. The
      PPPS is designed to assess both penile self-perception with regard to meatus,
      glans, skin and general appearance. The HOSE is a five-point scoring system
      designed to allow an objective appraisal of the outcome of hypospadias repair,
      based on evaluating meatal location, meatal shape, urinary stream, straightness
      of erection, and the presence and complexity of any complicating urethral
      fistula. RESULTS: Qmax were within age-adjusted references, independent of the
      surgical technique, with median (range) Qmax of 18.8 ml/s (range 3-45, n = 136).
      Patients expressed a high satisfaction for every single item of the penile
      perception scale (PPPS), with mean values between 2 (satisfied) and 3 (very
      satisfied). Eighty-two percent were satisfied or very satisfied of the overall
      evaluation of penile appearance. Eighty-one percent of patients had a normal
      erectile function (IIEF-5 >22; n = 35/43). CONCLUSIONS: Taking into account the
      limitation of a small number of patients resulting from a low 21% questionnaire's
      response rate, the results of this study align with previous reports from the
      literature and confirms that hypospadias repair using standard techniques results
      in acceptable functional, cosmetic and sexual outcomes. This study highlights the
      need of developing a set of standard approved outcomes assessments tools for
      evaluating the long-term impact of hypospadias repair performed in infancy.

PMID- 26201847
TI  - Whole-grain products and whole-grain types are associated with lower all-cause
      and cause-specific mortality in the Scandinavian HELGA cohort.
AB  - No study has yet investigated the intake of different types of whole grain (WG)
      in relation to all-cause and cause-specific mortality in a healthy population.
      The aim of the present study was to investigate the intake of WG products and WG
      types in relation to all-cause and cause-specific mortality in a large
      Scandinavian HELGA cohort that, in 1992-8, included 120 010 cohort members aged
      30-64 years from the Norwegian Women and Cancer Study, the Northern Sweden Health
      and Disease Study, and the Danish Diet Cancer and Health Study. Participants
      filled in a FFQ from which data on the intake of WG products were extracted. The
      estimation of daily intake of WG cereal types was based on country-specific
      products and recipes. Mortality rate ratios (MRR) and 95 % CI were estimated
      using the Cox proportional hazards model. A total of 3658 women and 4181 men died
      during the follow-up (end of follow-up was 15 April 2008 in the Danish sub
      cohort, 15 December 2009 in the Norwegian sub-cohort and 15 February 2009 in the
      Swedish sub-cohort). In the analyses of continuous WG variables, we found lower
      all-cause mortality with higher intake of total WG products (women: MRR 0.89 (95
      % CI 0.86, 0.91); men: MRR 0.89 (95 % CI 0.86, 0.91) for a doubling of intake).
      In particular, intake of breakfast cereals and non-white bread was associated
      with lower mortality. We also found lower all-cause mortality with total intake
      of different WG types (women: MRR 0.88 (95 % CI 0.86, 0.92); men: MRR 0.88 (95 %
      CI 0.86, 0.91) for a doubling of intake). In particular, WG oat, rye and wheat
      were associated with lower mortality. The associations were found in both women
      and men and for different causes of deaths. In the analyses of quartiles of WG
      intake in relation to all-cause mortality, we found lower mortality in the
      highest quartile compared with the lowest for breakfast cereals, non-white bread,
      total WG products, oat, rye (only men), wheat and total WG types. The MRR for
      highest v. lowest quartile of intake of total WG products was 0.68 (95 % CI 0.62,
      0.75, P trend over quartiles< 0.0001) for women and 0.75 (95 % CI 0.68, 0.81, P
      trend over quartiles< 0.0001) for men. The MRR for highest v. lowest quartile of
      intake of total WG types was 0.74 (95 % CI 0.67, 0.81, P trend over quartiles<
      0.0001) for women and 0.75 (95 % CI 0.68, 0.82, P trend over quartiles< 0.0001)
      for men. Despite lower statistical power, the analyses of cause-specific
      mortality according to quartiles of WG intake supported these results. In
      conclusion, higher intake of WG products and WG types was associated with lower
      mortality among participants in the HELGA cohort. The study indicates that intake
      of WG is an important aspect of diet in preventing early death in Scandinavia.

PMID- 26201848
TI  - The effect of prenatal education curriculum on mother's prenatal examination
      utilization, delivery mode and recovery status: a cross-sectional survey in
      China.
AB  - OBJECTIVES: To examine the participation, implementation, and effect of the
      prenatal education curriculum provided by hospitals in China, and to provide
      evidence for the improvement of prenatal education. METHODS: A cross-sectional
      survey was conducted in the hospitals in Hunan Province, China. Mothers aged 20
      45 years who had given birth between 1 May 2011 and 1 May 2012 and not diagnosed
      with pregnancy-related complications were invited to participate in the study. A
      self-administered, structured questionnaire was used to examine the effect of
      prenatal education curriculum on prenatal examination utilization, delivery mode,
      and recovery status from delivery. RESULTS: Among the total 604 respondents, only
      175 (29.1 %) surveyed mothers participated in prenatal education curriculum
      provided by hospitals during their latest delivery. These mothers had a higher
      rate of attending all the required prenatal examinations (57.9 vs. 48.3 %), and a
      higher rate of recovering very well and well (80 vs. 73.7 %) from the latest
      delivery, than those who did not participate in prenatal education curriculum (P
      < 0.05). However, there was no statistical difference in the delivery mode
      between mothers who participated and those who did not participate in the
      prenatal education curriculum provided by hospitals. CONCLUSIONS: Prenatal
      education is indispensable for the improvement of maternal and child health, and
      thus should be advocated. In China, a standard and convenient specification
      prenatal education curriculum provided by hospitals and their doctors is
      appropriated for providing prenatal education to pregnant women.

PMID- 26201849
TI  - The impacts of occupational risks and their effects on work stress levels of
      health professional (The sample from the Southeast region of Turkey).
AB  - OBJECTIVES: This study was performed to determine the occupational risks and
      their effects on the work stress of the health professionals working in state
      hospitals in the Southeast of Turkey. METHODS: This cross-sectional and
      descriptive study was composed of 360 health professionals of the Pazarcik,
      Ergani, and Sehitkamil State Hospitals between December 2014 and January 2015.
      The data of the study were obtained by performing the survey which was composed
      of questions related to the socio-demographic characteristics, factors that were
      thought to affect the occupational risks and job stress, as well as, the
      questions of the Work Stress Scale. The analyses of the data have been performed
      using Student's t test and one-way analysis of variance. RESULTS: The working
      hours, the number of being on-duty, insomnia, and burnout in health professionals
      were determined to be with the highest mean scores among other stressful risks
      and hazards. The mean work stress level, which increases the success by creating
      the group-stimulus effect, was indicated as 2.4 and 2.5 for the health
      professionals in Pazarcik and Ergani State Hospital, respectively. However, the
      stress level which poses a threat for the group-health and efficiency was found
      to be 4.0 for the health professionals of the Sehitkamil State Hospital.
      CONCLUSIONS: As the exposure of the occupational risks increases in the health
      professionals, the work stress scores also increase (p < 0.05). The occupational
      risks and work stress of the health professionals in the Sehitkamil State
      Hospital should be evaluated in terms of occupational health and safety.

PMID- 26201850
TI  - Monitoring the formation of cholesterol oxidation products in model systems using
      response surface methodology.
AB  - BACKGROUND: Cholesterol oxidation products (COPs) are produced during thermal
      processing of animal origin foods and are considered to have negative health
      impacts. The model systems are helpful to understand the impact of various
      factors on oxidation changes in foods during cooking process. METHODS: The study
      presented herein investigates the effects of pH, presence of unsaturated fatty
      acids, and heat on the formation of cholesterol oxidation products (COPs). Two
      model systems were designed to investigate the formation of cholesterol oxidation
      products in different lipid environments. The cholesterol oxides produced were
      quantified using gas chromatography. RESULTS: The level of cholesterol oxidation
      products decreased significantly at higher pH (above 5.8) and shorter heating
      time (3 h). The presence of unsaturated fatty acids (linoleic and oleic acids)
      significantly increased the amount of COPs under low-temperature heating
      conditions (100  degrees C and 1 h) but did not affect the production of COPs at
      higher temperature (150  degrees C). Increasing the temperature to 200  degrees C
      significantly increased the amount of COPs during the first hour of heating and
      this amount decreased upon further heating. The most frequently observed COPs in
      samples were alpha-epoxide, 20alpha-hydroxycholesterol, and 25
      hydroxycholesterol. CONCLUSIONS: In conclusion, pH below 5.8, presence of
      unsaturated fatty acid, and high cooking temperature (>150  degrees C) leads to
      increased production of cholesterol oxidation products.

PMID- 26201851
TI  - Safety of therapeutic hypothermia in children on veno-arterial extracorporeal
      membrane oxygenation after cardiac surgery - CORRIGENDUM.

PMID- 26201853
TI  - Linear accelerator-based stereotactic radiosurgery in 140 brain metastases from
      malignant melanoma.
AB  - BACKGROUND: To retrospectively access outcome and prognostic parameters of linear
      accelerator-based stereotactic radiosurgery in brain metastases from malignant
      melanoma. METHODS: Between 1990 and 2011 140 brain metastases in 84 patients with
      malignant melanoma (median age 56 years) were treated with stereotactic
      radiosurgery. At initial stereotactic radiosurgery 48 % of patients showed
      extracerebral control. The median count of brain metastases in a single patient
      was 1, the median diameter was 12 mm. The median dose applied was 20 Gy/80 %
      isodose enclosing. RESULTS: The median follow-up was 7 months and the median
      overall survival 9 months. The 6-, 12- and 24 month overall survival rates were
      71 %, 39 % and 25 % respectively. Cerebral follow-up imaging showed complete
      remission in 20 brain metastases, partial remission in 39 brain metastases,
      stable disease in 54 brain metastases, progressive disease in 24 brain metastases
      and pseudo-progression in 3 brain metastases. Median intracerebral control was
      5.3 months and the 6- and 12-month intracerebral progression-free survival rates
      48 % and 38 %, respectively. Upon univariate analysis, extracerebral control (log
      rank, p < 0.001), the response to stereotactic radiosurgery (log-rank, p <
      0.001), the number of brain metastases (log-rank, p = 0.007), the recursive
      partitioning analysis class (log-rank, p = 0.027) and the diagnosis-specific
      graded prognostic assessment score (log-rank, p = 0.011) were prognostic for
      overall survival. The most common clinical side effect was headache common
      toxicity criteria grade I. The most common radiological finding during follow-up
      was localized edema within the stereotactic radiosurgery high dose region.
      CONCLUSION: Stereotactic radiosurgery is a well-tolerated and effective treatment
      option for brain metastases in malignant melanoma and was able to achieve local
      remissions in several cases. Furthermore, especially patients with controlled
      extracerebral disease and a low count of brain metastases seem to benefit from
      this treatment modality. Prospective trials analysing the effects of combined
      stereotactic radiosurgery and new systemic agents are warranted.

PMID- 26201852
TI  - Antioxidant effects of Dendropanax morbifera Leveille extract in the hippocampus
      of mercury-exposed rats.
AB  - BACKGROUND: Dendropanax morbifera Leveille has been employed for the treatment of
      infectious diseases using folk medicine. In this study, we evaluated the
      antioxidant effects of a leaf extract of Dendropanax morbifera Leveille in the
      hippocampus of mercury-exposed rats. METHODS: Seven-week-old Sprague-Dawley rats
      received a daily intraperitoneal injection of 5 MUg/kg dimethylmercury and/or
      oral Dendropanax morbifera Leveille leaf extract (100 mg/kg) for 4 weeks. Animals
      were sacrificed 2 h after the last dimethylmercury and/or leaf extract treatment.
      Mercury levels were measured in homogenates of hippocampal tissue, a brain region
      that is vulnerable to mercury toxicity. In addition, we measured reactive oxygen
      species production, lipid peroxidation levels, and antioxidant levels in these
      hippocampal homogenates. RESULTS: Treatment with Dendropanax morbifera Leveille
      leaf extract significantly reduced mercury levels in hippocampal homogenates and
      attenuated the dimethylmercury-induced increase in the production of reactive
      oxygen species and formation of malondialdehyde. In addition, this leaf extract
      treatment significantly reversed the dimethylmercury-induced reduction in the
      hippocampal activities of Cu, Zn-superoxide dismutase, catalase, glutathione
      peroxidase, and glutathione-S-transferase. CONCLUSION: These results suggest that
      a leaf extract of Dendropanax morbifera Leveille had strong antioxidant effects
      in the hippocampus of mercury-exposed rats.

PMID- 26201854
TI  - Mitochondrial DNA T4216C and A4917G variations in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) affects the brain and spinal cord and long
      has been the topic of global research; yet there is no commonly accepted cause
      and no cure for the disease. Mounting evidence supports the role of genetics in
      susceptibility to MS. From this perspective, a current effort focuses on the
      neurogenetics of the complex pathogenesis of MS in relation to factors such as
      mitochondrial DNA (mtDNA) variations. T4216C and A4917G are common mitochondrial
      gene variations associated with MS. The present study tested whether mtDNA T4216C
      variation in the NADH Dehydrogenase 1 (ND1) mtDNA gene and A4917G variation in
      the mtDNA NADH Dehydrogenase 2 (ND2) gene are associated with MS in an Iranian
      population. MATERIAL AND METHODS: Blood samples were collected from 100 patients
      with MS and 100 unrelated healthy controls, and DNA extraction was performed by
      salting-out. By means of appropriate primers, polymerase chain reaction (PCR)
      amplification was carried out for the mtDNA fragment. Afterwards, the PCR
      products were digested using Nla III and Acc I restriction endonuclease enzymes
      for analysis of Restriction Fragment Length polymorphism (RFLP) in mtDNA T4216C
      and A4917G variations, respectively. With electrophoresis by means of 3% agarose
      gel and safe DNA gel stain, we imaged restriction products in a UV
      transilluminator. The accuracy of genotyping procedure was confirmed by
      sequencing the mtDNA fragment. RESULTS: No significant statistical difference in
      the frequency of the T4216C mtDNA variation was found between the patients (24%)
      and the control subjects (21%) (P=0.61). Logistic regression analysis showed an
      OR of 1.1 (95% CI=0.5-2.4). Moreover, there was no significant statistical
      difference in the frequency of mtDNA A4917G variation between the cases (11%) and
      the controls (9%) (P=0.637). Logistic regression analysis revealed an odds ratio
      (OR) of 1.2 with 95% CI of 0.4-3.5. CONCLUSION: The present study revealed no
      association between MS and T4216C variation in the ND1 mtDNA gene and A4917G
      variation in the mtDNA ND2 gene in the Iranian population.

PMID- 26201855
TI  - Ferulic acid exerts its antidiabetic effect by modulating insulin-signalling
      molecules in the liver of high-fat diet and fructose-induced type-2 diabetic
      adult male rat.
AB  - Ferulic acid (FA) is a phenolic phytochemical known for its antidiabetic property
      The present study is designed to evaluate the mechanism behind its antidiabetic
      property in high-fat and fructose-induced type 2 diabetic adult male rats.
      Animals were divided into 5 groups: (i) control, (ii) diabetic control, (iii)
      diabetic animals treated with FA (50 mg/(kg body weight . day)(-1), orally) for
      30 days, (iv) diabetic animals treated with metformin (50 mg/(kg body weight .
      day)(-1), orally) for 30 days, and (v) control rats treated with FA. FA treatment
      to diabetic animals restored blood glucose, serum insulin, glucose tolerance, and
      insulin tolerance to normal range. Hepatic glycogen concentration, activity of
      glycogen synthase, and glucokinase were significantly decreased, whereas activity
      of glycogen phosphorylase and enzymes of gluconeogenesis (phosphoenolpyruvate
      carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase)) were increased in
      diabetic animals and FA restored these to normal levels similar to that of
      metformin. FA improved the insulin signalling molecules and reduced the negative
      regulators of insulin signalling. The messenger RNA of gluconeogenic enzyme genes
      (PEPCK and G6Pase) and the interaction between forkhead transcription factor-O1
      and promoters of gluconeogenic enzyme genes (PEPCK and G6Pase) was reduced
      significantly by ferulic acid. It is concluded from the present study that FA
      treatment to type 2 diabetic rats improves insulin sensitivity and hepatic
      glycogenesis but inhibits gluconeogenesis and negative regulators of insulin
      signalling to maintain normal glucose homeostasis.

PMID- 26201857
TI  - Myostatin dysfunction impairs force generation in extensor digitorum longus
      muscle and increases exercise-induced protein efflux from extensor digitorum
      longus and soleus muscles.
AB  - Myostatin dysfunction promotes muscle hypertrophy, which can complicate
      assessment of muscle properties. We examined force generating capacity and
      creatine kinase (CK) efflux from skeletal muscles of young mice before they reach
      adult body and muscle size. Isolated soleus (SOL) and extensor digitorum longus
      (EDL) muscles of Berlin high (BEH) mice with dysfunctional myostatin, i.e.,
      homozygous for inactivating myostatin mutation, and with a wild-type myostatin
      (BEH+/+) were studied. The muscles of BEH mice showed faster (P < 0.01) twitch
      and tetanus contraction times compared with BEH+/+ mice, but only EDL displayed
      lower (P < 0.05) specific force. SOL and EDL of age-matched but not younger BEH
      mice showed greater exercise-induced CK efflux compared with BEH+/+ mice. In
      summary, myostatin dysfunction leads to impairment in muscle force generating
      capacity in EDL and increases susceptibility of SOL and EDL to protein loss after
      exercise. 

PMID- 26201856
TI  - Influence of ageing and essential amino acids on quantitative patterns of
      troponin T alternative splicing in human skeletal muscle.
AB  - Ageing is associated with a loss of skeletal muscle performance, a condition
      referred to as sarcopenia. In part, the age-related reduction in performance is
      due to a selective loss of muscle fiber mass, but mass-independent effects have
      also been demonstrated. An important mass-independent determinant of muscle
      performance is the pattern of expression of isoforms of proteins that participate
      in muscle contraction (e.g., the troponins). In the present study, we tested the
      hypothesis that ageing impairs alternative splicing of the pre-mRNA encoding fast
      skeletal muscle troponin T (TNNT3) in human vastus lateralis muscle. Furthermore,
      we hypothesized that resistance exercise alone or in combination with consumption
      of essential amino acids would attenuate age-associated effects on TNNT3
      alternative splicing. Our results indicate that ageing negatively affects the
      pattern of TNNT3 alternative splicing in a manner that correlates quantitatively
      with age-associated reductions in muscle performance. Interestingly, whereas
      vastus lateralis TNNT3 alternative splicing was unaffected by a bout of
      resistance exercise 24 h prior to muscle biopsy, ingestion of a mixture of
      essential amino acids after resistance exercise resulted in a significant shift
      in the pattern of TNNT3 splice form expression in both age groups to one
      predicted to promote greater muscle performance. We conclude that essential amino
      acid supplementation after resistance exercise may provide a means to reduce
      impairments in skeletal muscle quality during ageing in humans.

PMID- 26201858
TI  - Measuring gross motor activities in Rett syndrome.

PMID- 26201859
TI  - Tear film proteins deposited on high water content contact lenses identified with
      two-dimensional gel electrophoresis and mass spectrometry.
AB  - PURPOSE: Tear film proteins adhere to the surface of contact lenses (CLs). While
      the proteins in the tears have been extensively studied with various proteomic
      techniques, adhered proteins to CLs are less studied. In this pilot study, we
      have separated proteins with 2D gel electrophoresis prior to the conventional
      mass spectrometry (MS) in order to analyse the deposited proteins on hydrogel CLs
      from myopic patients. METHODS: pHEMA and PVA hydrogel CLs worn by 3 patients for
      different time lengths were analysed. After wear, the CLs were frozen at -20
      degrees C. Proteins were extracted in lysis buffer, separated on 12%
      polyacrylamide gels and silver-stained. Protein spots were excised and identified
      with liquid chromatography - tandem MS. RESULTS: Deposited proteins were
      extracted with a yield of 26-66 MUg and separated by 2D gel electrophoresis. The
      silver-stained gels showed similar protein patterns independent of the patient,
      hydrogel type and wear time. Seventy-two spots were analysed with MS,
      representing at least 12 different tear film proteins or protein fragments.
      CONCLUSIONS: Deposited tear film proteins from a single set of CLs worn for 1 day
      can successfully be analysed first with 2D gel electrophoresis and subsequently
      with MS, thus making examination of individual patients possible. The protein
      composition appeared homogeneous between the test persons which is a necessity
      for additional comparison analysis. The molecular masses of the identified
      proteins indicate that protein degradation occurs only as a minor event. Myopic
      patients were investigated in this pilot study, but the combined techniques can
      easily be applied to other eye diseases.

PMID- 26201860
TI  - Purulent pericarditis and pericardiac tamponade in a pregnant hemodialysis
      patient: A case report.
AB  - Bacterial pericarditis is rare in chronic hemodialysis and has poor prognosis. In
      this case, we report a pregnant hemodialysis patient who developed purulent
      bacterial pericarditis and pericardiac tamponade in the 28th week of her
      pregnancy, and who had delivered a healthy living baby. 

PMID- 26201861
TI  - Exploiting Stem Cell-Extracellular Matrix Interactions for Cartilage
      Regeneration: A Focus on Basement Membrane Molecules.
AB  - The extracellular matrix (ECM) is a complex network of proteins and
      glycosaminoglycans which surrounds cells and serves a critical role in directing
      cell fate and functions, as well as imparting the necessary mechanical behaviour
      to the tissue. To achieve successful cartilage regeneration, stem cells and/or
      progenitor cells have to be able to undergo an orderly spatiotemporal
      differentiation process, along with specific changes in the ECM expression and
      deposition, to form a cartilage tissue with the defined hierarchical matrix
      organization. In the last decade, significant advances have been made in our
      understanding of the role of the ECM during chondrogenesis and in cartilage
      homeostasis following differentiation, with some unexpected findings. This review
      will survey the major ECM components and their interactions with relevant stem
      cell populations for the regeneration of cartilage. Future therapies will likely
      benefit from a better understanding and a more precise control of stem cell-ECM
      interactions implicated in the regenerative response.

PMID- 26201862
TI  - Towards Personalized Regenerative Cell Therapy: Mesenchymal Stem Cells Derived
      from Human Induced Pluripotent Stem Cells.
AB  - Mesenchymal stem cells (MSCs) are adult stem cells with the capacity of self
      renewal and multilineage differentiation, and can be isolated from several adult
      tissues. However, isolating MSCs from adult tissues for cell therapy is hampered
      by the invasive procedure, the rarity of the cells and their attenuated
      proliferation capacity when cultivated and expanded in vitro. Human MSCs derived
      from induced pluripotent stem cells (iPSC-MSCs) have now evolved as a promising
      alternative cell source for MSCs and regenerative medicine. Several groups,
      including ours, have reported successful derivation of functional iPSC-MSCs and
      applied these cells in MSC-based therapeutic testing. Still, the current
      experience and understanding of iPSC-MSCs with respect to production methods,
      safety and efficacy are primitive. In this review, we highlight the
      methodological progress in iPSC-MSC research, describing the importance of
      choosing the right sources of iPSCs, iPSC reprogramming methods, iPSC culture
      systems, embryoid body intermediates, pathway inhibitors, basal medium, serum,
      growth factors and culture surface coating. We also highlight some progress in
      the application of iPSC-MSCs in direct cell therapy, tissue engineering and gene
      therapy. 

PMID- 26201863
TI  - iPS cell transplantation for traumatic spinal cord injury.
AB  - A large body of work has been published on transplantation of a wide range of
      neural stem and progenitor cell types derived from the developing and adult CNS,
      as well as from pluripotent embryonic stem cells, in models of traumatic spinal
      cord injury (SCI). However, many of these cell-based approaches present practical
      issues for clinical translation such as ethical cell derivation, generation of
      potentially large numbers of homogenously prepared cells, and immune rejection.
      With the advent of induced Pluripotent Stem (iPS) cell technology, many of these
      issues may potentially be overcome. To date, a number of studies have
      demonstrated integration, differentiation into mature CNS lineages, migration and
      long-term safety of iPS cell transplants in a variety of SCI models, as well as
      therapeutic benefits in some cases. Given the clinical potential of this advance
      in stem cell biology, we present a concise review of studies published to date
      involving iPS cell transplantation in animal models of SCI. 

PMID- 26201865
TI  - Cross-Talking Between PPAR and WNT Signaling and its Regulation in Mesenchymal
      Stem Cell Differentiation.
AB  - The pluripotent mesenchymal stem cells (MSC) are common precursors to adipocytes
      and osteoblasts. Large numbers of extracellular and intracellular signals and
      transcription factors moderate adipogenesis and osteoblastogenesis. Importantly,
      between adipogenic and osteogenic lineage commitment and differentiation,
      differentiation of MSCs into one lineage will inhibit their differentiation
      toward the other lineage. This balance is regulated by numerous signaling
      pathways. As we know, the peroxisome-proliferator-activated receptor-gamma (PPAR
      gamma) and Wnt/beta-catenin pathway are regarded as the master moderators of
      adipogenesis and osteogenesis. Moreover, governing the differentiation of MSCs to
      adipogenesis and osteoblastogenesis has significant implications in diverse areas
      of human health, from obesity to regenerative medicine to osteoporosis. Rivalry
      roles have been reported of the two pathways since the downstream products
      activated by Wnt-5a repress PPAR-gamma transactivation through the H3K9 histone
      methyltransferase protein complexes. This review will discuss the inductive and
      inhibitive role of PPAR-gamma in adipogenesis and osteoblastogenesis
      respectively, as well as the canonical Wnt/beta-catenin pathway. 

PMID- 26201866
TI  - Comparison of Statistical Methods for Assessing Spatial Correlations Between Maps
      of Different Arterial Properties.
AB  - Assessing the anatomical correlation of atherosclerosis with biomechanical
      localizing factors is hindered by spatial autocorrelation (SA), wherein
      neighboring arterial regions tend to have similar properties rather than being
      independent, and by the use of aggregated data, which artificially inflates
      correlation coefficients. Resampling data at lower resolution or reducing degrees
      of-freedom in significance tests negated effects of SA but only in artificial
      situations where it occurred at a single length scale. Using Fourier or wavelet
      transforms to generate autocorrelation-preserving surrogate datasets, and thus to
      compute the null distribution, avoided this problem. Bootstrap methods
      additionally circumvented the errors caused by aggregating data. The bootstrap
      technique showed that wall shear stress (WSS) was significantly correlated with
      atherosclerotic lesion frequency and endothelial nuclear elongation, but not with
      the permeability of the arterial wall to albumin, in immature rabbits. 

PMID- 26201864
TI  - Research Advancements in Porcine Derived Mesenchymal Stem Cells.
AB  - In the present era of stem cell biology, various animals such as Mouse, Bovine,
      Rabbit and Porcine have been tested for the efficiency of their mesenchymal stem
      cells (MSCs before their actual use for stem cell based application in humans.
      Among them pigs have many similarities to humans in the form of organ size,
      physiology and their functioning, therefore they have been considered as a
      valuable model system for in vitro studies and preclinical assessments. Easy
      assessability, few ethical issues, successful MSC isolation from different
      origins like bone marrow, skin, umbilical cord blood, Wharton's jelly,
      endometrium, amniotic fluid and peripheral blood make porcine a good model for
      stem cell therapy. Porcine derived MSCs (pMSCs have shown greater in vitro
      differentiation and transdifferention potential towards mesenchymal lineages and
      specialized lineages such as cardiomyocytes, neurons, hepatocytes and pancreatic
      beta cells. Immunomodulatory and low immunogenic profiles as shown by autologous
      and heterologous MSCs proves them safe and appropriate models for
      xenotransplantation purposes. Furthermore, tissue engineered stem cell constructs
      can be of immense importance in relation to various osteochondral defects which
      are difficult to treat otherwise. Using pMSCs successful treatment of various
      disorders like Parkinson's disease, cardiac ischemia, hepatic failure, has been
      reported by many studies. Here, in this review we highlight current research
      findings in the area of porcine mesenchymal stem cells dealing with their
      isolation methods, differentiation ability, transplantation applications and
      their therapeutic potential towards various diseases. 

PMID- 26201867
TI  - Pushing back the limits of Raman imaging by coupling super-resolution and
      chemometrics for aerosols characterization.
AB  - The increasing interest in nanoscience in many research fields like physics,
      chemistry, and biology, including the environmental fate of the produced nano
      objects, requires instrumental improvements to address the sub-micrometric
      analysis challenges. The originality of our approach is to use both the super
      resolution concept and multivariate curve resolution (MCR-ALS) algorithm in
      confocal Raman imaging to surmount its instrumental limits and to characterize
      chemical components of atmospheric aerosols at the level of the individual
      particles. We demonstrate the possibility to go beyond the diffraction limit with
      this algorithmic approach. Indeed, the spatial resolution is improved by 65% to
      achieve 200 nm for the considered far-field spectrophotometer. A multivariate
      curve resolution method is then coupled with super-resolution in order to explore
      the heterogeneous structure of submicron particles for describing physical and
      chemical processes that may occur in the atmosphere. The proposed methodology
      provides new tools for sub-micron characterization of heterogeneous samples using
      far-field (i.e. conventional) Raman imaging spectrometer. 

PMID- 26201868
TI  - SLAP: Small Labeling Pair for Single-Molecule Super-Resolution Imaging.
AB  - Protein labeling with synthetic fluorescent probes is a key technology in
      chemical biology and biomedical research. A sensitive and efficient modular
      labeling approach (SLAP) was developed on the basis of a synthetic small-molecule
      recognition unit (Ni-trisNTA) and the genetically encoded minimal protein His6-10
      -tag. High-density protein tracing by SLAP was demonstrated. This technique
      allows super-resolution fluorescence imaging and fulfills the necessary sampling
      criteria for single-molecule localization-based imaging techniques. It avoids
      masking by large probes, for example, antibodies, and supplies sensitive,
      precise, and robust size analysis of protein clusters (nanodomains). 

PMID- 26201870
TI  - Differentiating sepsis from non-infectious systemic inflammation based on
      microvesicle-bacteria aggregation.
AB  - Sepsis is a severe medical condition and a leading cause of hospital mortality.
      Prompt diagnosis and early treatment has a significant, positive impact on
      patient outcome. However, sepsis is not always easy to diagnose, especially in
      critically ill patients. Here, we present a conceptionally new approach for the
      rapid diagnostic differentiation of sepsis from non-septic intensive care unit
      patients. Using advanced microscopy and spectroscopy techniques, we measure
      infection-specific changes in the activity of nano-sized cell-derived
      microvesicles to bind bacteria. We report on the use of a point-of-care
      compatible microfluidic chip to measure microvesicle-bacteria aggregation and
      demonstrate rapid (<=1.5 hour) and reliable diagnostic differentiation of
      bacterial infection from non-infectious inflammation in a double-blind pilot
      study. Our study demonstrates the potential of microvesicle activities for sepsis
      diagnosis and introduces microvesicle-bacteria aggregation as a potentially
      useful parameter for making early clinical management decisions. 

PMID- 26201869
TI  - Suppression of SHIP2 contributes to tumorigenesis and proliferation of gastric
      cancer cells via activation of Akt.
AB  - BACKGROUND: The Src homology 2-containing inositol 5-phosphatase 2 (SHIP2) is
      implicated in diabetes, arthrosclerosis, and cancer. However, the role of SHIP2
      in human gastric cancer remains unclear. METHODS: The expression levels of SHIP2
      in gastric cancer tissues, a panel of gastric cancer cell lines, and normal
      gastric epithelial cells were analyzed by immunohistochemistry (IHC), Western
      blot, and real-time quantitative RT-PCR (qRT-PCR). Gastric cancer cells with
      either overexpressed SHIP2 or co-overexpressed SHIP2 and Akt were analyzed to
      determine cell proliferation, colony formation, apoptosis, cell migration, and
      invasion assays. Normal gastric epithelial cells with knockdown SHIP2 or co
      knockdown SHIP2 and Akt were subjected by anchorage-independent growth assays.
      The effect of SHIP2 on tumor growth in vivo was detected by xenograft
      tumorigenesis assays. RESULTS: SHIP2 was commonly downregulated in gastric cancer
      compared with normal gastric mucosa, and overexpression of SHIP2 inhibited cell
      proliferation, induced apoptosis, suppressed cell motility and invasion in
      gastric cancer cells in vitro, and retarded the growth of xenograft gastric
      tumors in vivo, while knockdown of SHIP2 in normal gastric epithelial cells
      promoted anchorage-independent growth. Moreover, overexpression of SHIP2
      inactivated Akt, and upregulated p21, p27, and the pro-apoptotic protein Bim.
      Restoring Akt activation in gastric cancer cells largely blocked the inhibition
      of PI3K/Akt signaling by SHIP2 and reversed the inhibitory effect of SHIP2 on
      tumorigenesis and proliferation. CONCLUSIONS: This study demonstrates, for the
      first time, that SHIP2 is frequently downregulated in gastric cancer, and reduced
      SHIP2 expression promotes tumorigenesis and proliferation of gastric cancer via
      activation of the PI3K/Akt signaling.

PMID- 26201871
TI  - Erratum to: Water intake: validity of population assessment and recommendations.

PMID- 26201872
TI  - Polyunsaturated fatty acid intake and risk of cardiovascular mortality in a low
      fish-consuming population: a prospective cohort analysis.
AB  - PURPOSE: The aim of this study was to examine the relationship between
      polyunsaturated fatty acids (PUFA) intake (n-6 and n-3) and mortality in a
      population-based sample with a low fish intake. METHODS: Cox regression was used
      to examine the relationships between dietary PUFA intake and all-cause or CVD
      mortality in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab)
      cohort, a population of 11,247 Australians aged >=25 years recruited in 1999/2000
      and followed until 2012. Demographic, lifestyle and behavioural information were
      collected by questionnaire and fasting blood tests undertaken. Dietary intake was
      collected by a 121-item food frequency questionnaire. Vital status and causes of
      death were collected by death registry linkage. RESULTS: Those in the highest
      quintile of n-6 PUFA intake had lower risk of CVD mortality (HR 0.57, 95 % CI
      0.38-0.86) after age and sex adjustment, but this failed to retain significance
      after further risk factor adjustment. Consumption of >=1 serves/week of non-fried
      fish was associated with reduced risk of CVD mortality (HR 0.64, 95 % CI 0.45
      0.91, p = 0.013) compared to those eating less than 1 serve/month, after sex and
      age adjustment, but did not retain significance after further adjustment.
      However, long-chain n-3 intake was not associated with CVD mortality, and those
      in the highest quintile of n-3 intake had a higher risk of all-cause mortality.
      CONCLUSIONS: These findings do not support previous suggestions that n-6 PUFA
      have adverse effects on CVD risk. Greater intake of non-fried fish was associated
      with lower risk of CVD mortality, but those with the highest total n-3 intake
      were at slightly increased risk of all-cause mortality.

PMID- 26201873
TI  - Pectin supplementation in rats mitigates age-related impairment in insulin and
      leptin sensitivity independently of reducing food intake.
AB  - SCOPE: This study investigates whether pectin supplementation in adult rats can
      ameliorate age-associated disturbances in peripheral insulin and leptin actions.
      METHODS AND RESULTS: Seven-month-old male Wistar rats were divided into three
      groups: control (rats fed ad libitum a standard-diet), pectin (rats fed ad
      libitum a standard-diet supplemented with 10% pectin), and pair-fed (rats pair
      fed to the pectin group). They were sacrificed after 1 month. Pectin and pair-fed
      rats showed lower body weight gain and food intake than controls and underwent a
      decrease in leptin levels and an increase in adiponectin levels. Pectin-treated
      animals, but not pair-fed ones, showed lower body-fat content and HOMA-IR index
      after dietary intervention. Compared to controls, pectin-treated rats showed a
      decline in the expression of genes related to energy uptake (WAT) and lipogenesis
      (WAT and liver), and increased expression levels of lipolysis- and fatty-acid
      oxidation-related genes (liver). Some of the changes were not evidenced in the
      pair-fed group. These effects appear to be associated with improved leptin
      signaling. CONCLUSION: Ten percent pectin supplementation for 1 month in adult
      rats decreases body-fat content and ameliorates age-related insulin and leptin
      resistance more intensely than what could be attributed to the decrease in energy
      intake, overall contributing to better metabolic health.

PMID- 26201874
TI  - One-dimensional porous nanofibers of Co3O4 on the carbon matrix from human hair
      with superior lithium ion storage performance.
AB  - One-dimensional (1D) hierarchical porous nanofibers of Co3O4 possessing of (220)
      facets on the carbon matrix from human hair (H2@Co3O4) with 20-30 nm in width and
      3-5 MUm in length are prepared by a facile solvothermal and calcination approach.
      The well crystallized small Co3O4 particles with the diameter of about 8-12 nm
      were closely aggregated together in the nanofibers. Electrochemical analyses show
      that the first discharge capacity of H2@Co3O4 electrode is 1368 mAh g(-1) at the
      current density of 0.1 A g(-1) based on the total mass of composite. A high
      reversible capacity of 916 mAh g (-1) was obtained over 100 cycles at 0.1 A g(
      1), presenting a good cycling stability. When cycled at a high current density of
      1 and 2 A g(-1), the specific capacity of 659 and 573 mAh g(-1) could be still
      achieved, respectively, indicating a superior power capability. 

PMID- 26201876
TI  - Multi-sensor super-resolution for hybrid range imaging with application to 3-D
      endoscopy and open surgery.
AB  - In this paper, we propose a multi-sensor super-resolution framework for hybrid
      imaging to super-resolve data from one modality by taking advantage of additional
      guidance images of a complementary modality. This concept is applied to hybrid 3
      D range imaging in image-guided surgery, where high-quality photometric data is
      exploited to enhance range images of low spatial resolution. We formulate super
      resolution based on the maximum a-posteriori (MAP) principle and reconstruct high
      resolution range data from multiple low-resolution frames and complementary
      photometric information. Robust motion estimation as required for super
      resolution is performed on photometric data to derive displacement fields of
      subpixel accuracy for the associated range images. For improved reconstruction of
      depth discontinuities, a novel adaptive regularizer exploiting correlations
      between both modalities is embedded to MAP estimation. We evaluated our method on
      synthetic data as well as ex-vivo images in open surgery and endoscopy. The
      proposed multi-sensor framework improves the peak signal-to-noise ratio by 2 dB
      and structural similarity by 0.03 on average compared to conventional single
      sensor approaches. In ex-vivo experiments on porcine organs, our method achieves
      substantial improvements in terms of depth discontinuity reconstruction. 

PMID- 26201877
TI  - Optical coherence tomography angiography during follow-up: qualitative and
      quantitative analysis of mixed type I and II choroidal neovascularization after
      vascular endothelial growth factor trap therapy.
AB  - PURPOSE: To report the optical coherence tomography angiography (OCT-A) findings
      in an exudative age-related macular degeneration (AMD) patient presenting mixed
      type I and II choroidal neovascularization (CNV) during follow-up after
      intravitreal vascular endothelial growth factor (VEGF) trap treatment. METHODS:
      The clinical assessment included both traditional multimodal imaging, based on
      fluorescein angiography (FA), indocyanine green angiography (ICGA) and B-scan
      OCT, and OCT-A at baseline and follow-up. OCT-A images were obtained using a
      Spectralis OCT-A prototype able to acquire 70,000 A-scans per second, with a
      resolution of 7 um axially and 14 um laterally. An amplitude decorrelation
      algorithm developed by Heidelberg Engineering was applied to a volume scan, on a
      15 * 5 degrees  area, which was composed of 131 B-scans (35 frames per scan) at a
      distance of 11 um each. The borders of type I and type II CNV were manually
      outlined and then the areas were analyzed using the provided automated software
      before and after treatment. RESULTS: The qualitative approach revealed a
      substantial decrease in the visibility of tiny branching vessels and anastomoses
      both in type I and type II components of the neovascular complex, associated with
      persistence of a clear hyperintense signal coming from the larger trunks, which
      remained well-perfused. Quantitative analysis confirmed a reduction of the lesion
      area after VEGF trap treatment: the type II component decreased from 0.25 to 0.19
      mm(2), while the type I component decreased from 2.03 to 1.80 mm(2). CONCLUSIONS:
      Our study qualitatively and quantitatively demonstrated the response of a mixed
      type I-II CNV to intravitreal VEGF trap therapy. Although FA remains the gold
      standard for determining the presence of leakage and OCT easily shows fluid
      accumulation and its variations, OCT-A offers noninvasive monitoring of the
      retinal and choriocapillaris microvasculature in patients with CNV, aiding in
      diagnosis and treatment decisions during follow-up.

PMID- 26201878
TI  - Mighty linkers.

PMID- 26201875
TI  - Multi-atlas segmentation of biomedical images: A survey.
AB  - Multi-atlas segmentation (MAS), first introduced and popularized by the
      pioneering work of Rohlfing, et al. (2004), Klein, et al. (2005), and Heckemann,
      et al. (2006), is becoming one of the most widely-used and successful image
      segmentation techniques in biomedical applications. By manipulating and utilizing
      the entire dataset of "atlases" (training images that have been previously
      labeled, e.g., manually by an expert), rather than some model-based average
      representation, MAS has the flexibility to better capture anatomical variation,
      thus offering superior segmentation accuracy. This benefit, however, typically
      comes at a high computational cost. Recent advancements in computer hardware and
      image processing software have been instrumental in addressing this challenge and
      facilitated the wide adoption of MAS. Today, MAS has come a long way and the
      approach includes a wide array of sophisticated algorithms that employ ideas from
      machine learning, probabilistic modeling, optimization, and computer vision,
      among other fields. This paper presents a survey of published MAS algorithms and
      studies that have applied these methods to various biomedical problems. In
      writing this survey, we have three distinct aims. Our primary goal is to document
      how MAS was originally conceived, later evolved, and now relates to alternative
      methods. Second, this paper is intended to be a detailed reference of past
      research activity in MAS, which now spans over a decade (2003-2014) and entails
      novel methodological developments and application-specific solutions. Finally,
      our goal is to also present a perspective on the future of MAS, which, we
      believe, will be one of the dominant approaches in biomedical image segmentation.

PMID- 26201879
TI  - DNA-linked superlattices get into shape.

PMID- 26201885
TI  - DNA-nanoparticle crystals: Flip-flop lattices.

PMID- 26201886
TI  - DNA-nanoparticle crystals: Exploiting shape complementarity.

PMID- 26201887
TI  - Material witness: Liquid-state particle physics.

PMID- 26201888
TI  - Superconductivity: The FeSe riddle.

PMID- 26201890
TI  - Photonics: Trapped in a flat dispersion.

PMID- 26201889
TI  - Dislocation networks: Shedding coherent light on defects.

PMID- 26201891
TI  - Shape memory alloys: Towards practical actuators.

PMID- 26201893
TI  - A new look at stress: abscisic acid patterns and dynamics at high-resolution.
AB  - Abscisic acid (ABA) is a key phytohormone promoting abiotic stress tolerance as
      well as developmental processes such as seed dormancy. A spatiotemporal map of
      ABA concentrations would greatly advance our understanding of the cell type and
      timing of ABA action. Organ and tissue-level ABA measurements, as well as
      indirect in vivo measurements such as cell-specific transcriptional analysis of
      ABA metabolic enzymes and ABA-responsive promoters, have all contributed to
      current views of the localization and timing of ABA accumulations. Recently
      developed Forster resonance energy transfer (FRET) biosensors for ABA that sense
      ABA levels directly promise to add unprecedented resolution to in vivo ABA
      spatiotemporal mapping and expand our knowledge of the mechanisms controlling ABA
      levels in space and time.

PMID- 26201892
TI  - Molecular-based design and emerging applications of nanoporous carbon spheres.
AB  - Over the past decade, considerable progress has been made in the synthesis and
      applications of nanoporous carbon spheres ranging in size from nanometres to
      micrometres. This Review presents the primary techniques for preparing nanoporous
      carbon spheres and the seminal research that has inspired their development,
      presented potential applications and uncovered future challenges. First we
      provide an overview of the synthesis techniques, including the Stober method and
      those based on templating, self-assembly, emulsion and hydrothermal
      carbonization, with special emphasis on the design and functionalization of
      nanoporous carbon spheres at the molecular level. Next, we cover the key
      applications of these spheres, including adsorption, catalysis, separation,
      energy storage and biomedicine - all of which might benefit from the regular
      geometry, good liquidity, tunable porosity and controllable particle-size
      distribution offered by nanoporous carbon spheres. Finally, we present the
      current challenges and opportunities in the development and commercial
      applications of nanoporous carbon spheres.

PMID- 26201894
TI  - Peroxisomal Disorders: A Review on Cerebellar Pathologies.
AB  - Peroxisomes are organelles with diverse metabolic tasks including essential roles
      in lipid metabolism. They are of utmost importance for the normal functioning of
      the nervous system as most peroxisomal disorders are accompanied with
      neurological symptoms. Remarkably, the cerebellum exquisitely depends on intact
      peroxisomal function both during development and adulthood. In this review, we
      cover all aspects of cerebellar pathology that were reported in peroxisome
      biogenesis disorders and in diseases caused by dysfunction of the peroxisomal
      alpha-oxidation, beta-oxidation or ether lipid synthesis pathways. We also
      discuss the phenotypes of mouse models in which cerebellar pathologies were
      recapitulated and search for connections with the metabolic abnormalities. It
      becomes increasingly clear that besides the most severe forms of peroxisome
      dysfunction that are associated with developmental cerebellar defects, milder
      impairments can give rise to ataxia later in life. 

PMID- 26201895
TI  - MicroRNA-138 negatively regulates non-small cell lung cancer cells through the
      interaction with cyclin D3.
AB  - Previous studies demonstrate that microRNA-138 (miR-138) is critical in non-small
      cell lung cancer (NSCLC) regulation. We further explored the molecular mechanism
      of miR-138 in NSCLC. Lentivirus was used to upregulate miR-138 in NSCLC cell
      lines H460 and SPC-A1 cells. Previously known effects of miR-138 upregulation on
      NSCLC, proliferation, cell cycle division, and cisplatin sensitivity were
      examined in H460 and SPC-A1 cells. Moreover, previously unknown effect of miR-138
      upregulation on NSCLC migration was also examined in H460 and SPC-A1 cells. A new
      miR-138 downstream target, cyclin D3 (CCND3), was assessed by dual-luciferase
      reporter assay and quantitative real-time PCR (qRT-PCR). CCND3 was then
      ectopically overexpressed in H460 and SPC-A1 cells. The effects of forced
      overexpression of CCND3 on miR-138-induced NSCLC regulations were further
      examined by proliferation, cell cycle, cisplatin sensitivity, and migration
      assays, respectively. Lentivirus-induced miR-138 upregulation inhibited NSCLC
      proliferation and cell cycle division, in line with previous findings. Moreover,
      we found that miR-138 upregulation had other anti-tumor effects, such as
      increasing cisplatin sensitivity and reducing cancer migration, in H460 and SPC
      A1 cells. Luciferase assay and qRT-PCR showed that CCND3 was directly targeted by
      miR-138. Forced overexpression of CCND3 in H460 and SPC-A1 cells reversed the
      anti-tumor effects of miR-138 upregulation on cancer cell growth, cell cycle,
      cisplatin sensitivity, and migration. Our study revealed novel anti-cancer
      effects of miR-138 upregulation in NSCLC, as well as its new molecular target of
      CCND3. 

PMID- 26201896
TI  - Erratum to: CIP2A mediates prostate cancer progression via the c-MYC signaling
      pathway.

PMID- 26201897
TI  - Serine-arginine protein kinase 1 is associated with hepatocellular carcinoma
      progression and poor patient survival.
AB  - The pre-mRNA splicing regulator serine-arginine protein kinase 1 (SRPK1) promotes
      cancer development and various pathophysiological processes. However, the
      clinical relevance of SRPK1 in hepatocellular carcinoma (HCC) is not clear. This
      study investigates the expression and prognostic value of SRPK1 in HCC. We found
      that SRPK1 expression was significantly upregulated at the mRNA and protein level
      in all HCC cell lines or HCC tissue samples compared with the hepatic cell line
      or matched noncancerous tissue samples, respectively. Higher SRPK1 expression
      significantly correlated with clinical staging (p = 0.031), survival time (p =
      0.004), and gender (p = 0.011) of HCC patients. Together, our study showed that
      SRPK1 is overexpressed in HCC and may be a promising indicator of prognosis for
      HCC patients. 

PMID- 26201898
TI  - Pituitary tumor-transforming gene 1 regulates invasion of prostate cancer cells
      through MMP13.
AB  - It is critical to understand the molecular mechanisms underlying the migration
      and invasiveness of prostate cancer (PC) for improving the outcome of therapy. A
      relationship of pituitary tumor-transforming gene 1 (Pttg1) and matrix
      metalloproteinase 13 (MMP13) in PC as well as their roles in the metastases of PC
      has not been studied. Here, we reported significantly higher levels of Pttg1 and
      MMP13 in the resected PC specimens, compared to the adjacent normal prostate
      tissue from the same patient. Interestingly, Pttg1 and MMP13 levels strongly
      correlated with each other. In vitro, Pttg1 activated MMP13, which determined PC
      cell invasiveness. However, Pttg1 levels were not significantly affected by
      MMP13. Furthermore, the Pttg1-activated MMP13 in PC cells was significantly
      suppressed by inhibition of PI3k/Akt, but not ERK/MAPK or JNK pathways. Together,
      our data suggest that Pttg1 may increase PC cell metastasis by MMP13, and
      highlight Pttg1/MMP13 axis as a promising therapeutic target for PC treatment.

PMID- 26201899
TI  - CRUK Invests L15 Million in Research Hubs.

PMID- 26201901
TI  - Role of 5-HT(2B) Serotonin Receptor Agonist in the Regulation of Pumping Function
      of the Heart.
AB  - The effect of alpha-methyl-5-hydroxytryptamine maleate, an agonist of 5-HT2B
      serotonin receptors, on the pumping function of the heart was examined in rats
      with forced motor behavior. At rest, swim-trained rats demonstrated lower HR and
      greater stroke volume and cardiac output than untrained rats. The agonist
      decreased HR, stroke volume, and cardiac output in 21- and 70-day-old swim
      trained rats, but not in 100- and 200-day-old rats. 

PMID- 26201902
TI  - Effects of Melatonin on Stress-Induced Changes in the Liver of Rats with
      Different Resistance to Stress.
AB  - Effects of melatonin on changes in the liver structures were studied in stress
      resistant and stress-sensitive rats exposed to chronic stress. It was found that
      the number of degenerative cells increased and intralobular sinusoidal capillary
      enlarged in the liver of animals of both groups. These parameters were
      significantly higher in stress-sensitive rats. Melatonin (1 mg/kg) reduced the
      severity of degenerative changes and stimulated the development of reparative
      processes in the liver tissue. The effects of the hormone was more pronounced in
      rats sensitive to stress and was noted after melatonin administration in a dose
      of 0.2 mg/kg. 

PMID- 26201900
TI  - Regulatory T-cell Response to Enterotoxigenic Bacteroides fragilis Colonization
      Triggers IL17-Dependent Colon Carcinogenesis.
AB  - Many epithelial cancers are associated with chronic inflammation. However, the
      features of inflammation that are procarcinogenic are not fully understood.
      Regulatory T cells (Treg) typically restrain overt inflammatory responses and
      maintain intestinal immune homeostasis. Their immune-suppressive activity can
      inhibit inflammation-associated cancers. Paradoxically, we show that colonic
      Tregs initiate IL17-mediated carcinogenesis in multiple intestinal neoplasia mice
      colonized with the human symbiote enterotoxigenic Bacteroides fragilis (ETBF).
      Depletion of Tregs in ETBF-colonized C57BL/6 FOXP3(DTR) mice enhanced colitis but
      diminished tumorigenesis associated with shifting of mucosal cytokine profile
      from IL17 to IFNgamma; inhibition of ETBF-induced colon tumorigenesis was
      dependent on reduced IL17 inflammation and was independent of IFNgamma. Treg
      enhancement of IL17 production is cell-extrinsic. IL2 blockade restored Th17
      responses and tumor formation in Treg-depleted animals. Our findings demonstrate
      that Tregs limit the availability of IL2 in the local microenvironment, allowing
      the Th17 development necessary to promote ETBF-triggered neoplasia, and thus
      unveil a new mechanism whereby Treg responses to intestinal bacterial infection
      can promote tumorigenesis. SIGNIFICANCE: Tregs promote an oncogenic immune
      response to a common human symbiote associated with inflammatory bowel disease
      and colorectal cancer. Our data define mechanisms by which mucosal Tregs, despite
      suppressing excessive inflammation, promote the earliest stages of immune
      procarcinogenesis via enhancement of IL17 production at the expense of IFNgamma
      production.

PMID- 26201904
TI  - Changes in Oxygen Partial Pressure in the Vitreous Body and Arterial Blood of
      Rabbits Depending on Oxygen Concentration in Inspired Mixture.
AB  - We demonstrated that the vitreous body of one-month-old rabbits becomes a
      "reservoir" for storage and accumulation of oxygen after exposure to additional
      oxygenation of the organism (O2 concentrations in inspired gas mixture were 40,
      60, 85, and 99%). The higher was O2 concentration in inspired mixture, the higher
      was oxygen saturation of the blood and vitreous body. O2 concentration of 40% was
      relatively safe for eye tissues. O2 concentration >60% induced oxygen
      accumulation in the vitreous body, which can be a provoking factor for the
      development of oxygen-induced pathologies. 

PMID- 26201903
TI  - Expression of Neuropeptides, Neurotrophins, and Neurotransmitters in the Skin of
      Patients with Atopic Dermatitis and Psoriasis.
AB  - Expression of neural marker PGP9.5, amphiregulin, semaphorin-3A, calcitonin gene
      related peptide and its receptor, nerve growth factor and its receptor, substance
      P and its receptor, and expression frequency were analyzed in biopsy specimens
      from patients with atopic dermatitis and psoriasis and healthy volunteers by
      immunohistochemical method. Nerve fibers penetrated into the epidermis more
      frequently, and amphiregulin expression was significantly higher in patients with
      atopic dermatitis and psoriasis comparing to the control. Expression of
      semaphorin-3A in patients with atopic dermatitis was less frequent than in the
      control. These findings reflect the involvement of amphiregulin and semaphorin-3A
      in the improvement of skin innervations and penetration of nerve fibers into the
      epidermis, and due of which these proteins mediate the development of itch. 

PMID- 26201905
TI  - Proliferative and Synthetic Activity of Nerve Cells after Combined or Individual
      Exposure to Hypoxia and Hypercapnia.
AB  - We compared synthetic and proliferative activity of brain cells in rats exposed
      hypoxia, hypercapnia, or both prior to experimental focal stroke. The mean number
      of nucleolus organizer regions in penumbra neurons did not change after
      normobaric hypoxia, but increased after permissive hypercapnia or hypercapnic
      hypoxia. These data attest to activation of proliferative and synthetic functions
      in nerve cells, which plays an important role in the neuroprotective mechanisms
      under conditions of combined exposure to hypoxia and hypercapnia. 

PMID- 26201906
TI  - Differences in Active Avoidance Conditioning in Male and Female Rats with
      Experimental Anxiety-Depressive Disorder.
AB  - Using rat model of experimental anxiety-depressive disorder caused by postnatal
      administration of methionyl-2(S)-cyanopyrrolidine, an inhibitor of dipeptidyl
      peptidase IV, we compared conditioned active avoidance response and memory
      retention in males and females. In experimental males and females, conditioning
      was impaired in comparison with the control. In experimental groups, females were
      worse learners than males, while in control groups, females were better learners
      than males. Memory retention in experimental animals did not differ from that in
      controls 24 h after learning. Two months after learning, control females
      demonstrated better retention than control males. 

PMID- 26201907
TI  - Modification of Anxious Behavior after Psychogenic Trauma and Treatment with
      Galanin Receptor Antagonist.
AB  - Effects of blockage of central galanin receptors on anxiety manifestations were
      studied in rats with psychogenic trauma. Psychogenic trauma was modeled by
      exposure of a group of rats to the situation when the partner was killed by a
      predator. Antagonist of galanin receptors was intranasally administered before
      stress exposure. Animal behavior was evaluated using the elevated-plus maze test,
      free exploratory paradigm, and open-field test. Psychogenic trauma was followed
      by an increase in anxiety level and appearance of agitated behavior. Blockage of
      galanin receptors aggravated behavioral impairment, which manifested in the
      pathological anxious reactions - manifestations of hypervigilance and
      hyperawareness. The results suggest that endogenous pool of galanin is involved
      into prevention of excessive CNS response to stressful stimuli typical of
      posttraumatic stress disorder.

PMID- 26201908
TI  - Effect of Antioxidant Echinochrome A on Bleomycin-Induced Pulmonary Fibrosis.
AB  - We studied the protective effect of antioxidant echinochrome A on bleomycin
      induced pulmonary fibrosis in rats at the early stages of postnatal ontogeny.
      Administration of echinochrome A was shown to reduce the severity of bleomycin
      induced oxidative stress in the lungs, prevented the development of hypertrophy
      of interalveolar connective tissue and peribronchial lymphoid infiltration, and
      normalized the ratio of volume densities of interalveolar septa and alveolar
      lumen.

PMID- 26201909
TI  - Erratum to: Coherent Fluctuation Nephelometry: A Rapid Method for Urine Screening
      for Bacterial Contamination.

PMID- 26201910
TI  - The Johann Jacob Wepfer Award 2015 of the European Stroke Conference to Professor
      Ralph L. Sacco.

PMID- 26201911
TI  - Confiding About Problems in Marriage and Long-Term Committed Relationships: A
      National Study.
AB  - This study examined confiding patterns in a national sample of 1000 U.S. adults
      aged 25-70 to inform the development of an educational program for confidants,
      called Marital First Responders. Results showed that 73% of U.S. adults have been
      a confidant to someone with a problem in a marriage or long-term committed
      relationship. The most common confiding relationship was between friends,
      followed by siblings. Confidants reported a wide range of problems brought to
      them, ranging from everyday complaints to serious issues such as infidelity and
      divorce. Confiders identified the most and least helpful responses. Findings
      suggest that naturally occurring confiding relationships have considerable
      potential to be the first level of help for troubled couple relationships. 

PMID- 26201912
TI  - "Testing your methyl": DNA methylation profiling of serum DNA of HCC patients.

PMID- 26201913
TI  - Role of cytokine levels in assessment of prognosis and post-treatment outcome in
      hepatocellular carcinoma.

PMID- 26201914
TI  - Detecting fibrosis without a liver biopsy: getting to the fat of the issue.
AB  - It is critical to assess the degree of liver fibrosis for clinical management.
      However, liver biopsy has many drawbacks and is invasive. Promising non-invasive
      methods including serum markers and new imaging studies to predict liver fibrosis
      have been developed in past decades. This editorial provides a succinct overview
      and update of the new non-invasive technologies, especially the three-dimensional
      magnetic resonance imaging (3-D MRI) that has been studied by Dr. Kawamura's
      group in Japan. It also highlights the merit and weakness of this 3D-MRI
      technology in predicting liver fibrosis and indicates future studies to
      understand where 3D-MRI fits into the current armamentarium of non-invasive serum
      based and imaging technologies. 

PMID- 26201915
TI  - Dopamine in the pathogenesis of minimal hepatic encephalopathy: a new player?

PMID- 26201916
TI  - CXC chemokine IP-10: a key actor in liver disease?
AB  - Interferon-gamma-inducible protein 10 (IP-10), or C-X-C motif chemokine (CXCL10),
      is a small cytokine belonging to the non-ELR CXC chemokine family. By binding to
      its specific receptor CXCR3, IP-10 recruits activated CXCR3+ T cells to the liver
      parenchyma and plays a pivotal role in liver disease initiation and progression.
      IP-10 is mainly secreted by hepatocytes and liver sinusoidal endothelium.
      Different IP-10 forms exert different functions: long-length IP-10 directs CXCR3+
      T cell migration and is associated with inflammation, while short IP-10 is a
      CXCR3 antagonist, thereby playing protective role in liver injury. IP-10 levels
      are positively associated with the severity of liver inflammation, fibrosis stage
      and acute graft rejection. High IP-10 levels are closely related to anti-HCV
      therapy failure. Thus, IP-10 may be both a potential prognostic tool and a
      therapeutic target for the treatment of patients with HCV or HIV/HCV co
      infection. The purpose of this review is to highlight the growing advances in
      basic knowledge and clinical interest of IP-10 in liver disease. 

PMID- 26201917
TI  - Small hepatocellular carcinoma: current and future approaches.
AB  - Over 3 decades have passed since the first report of small hepatocellular
      carcinoma (SHCC), which has been confirmed as one of the most significant
      prognostic factors. Obviously, it is indeed very important to know when an early
      SHCC will become more aggressive and lead to worse clinical outcome once it grows
      beyond a critical size. However, so far, no consensus has been achieved on the
      size criterion for SHCC among different authors or different clinical practice
      guidelines that have been used worldwide, although there are currently numerous
      cutoff values for tumor size used to define SHCC, including 5, 3 and 2 cm in
      diameter, etc. Herein, based on our current understanding concerning the
      pathobiological features of SHCC, we briefly review the history of SHCC study,
      analyze the advantages and limitations of the above criteria for SHCC, and
      discuss the pathobiological characteristics as well as the clinical significance
      of SHCC. 

PMID- 26201918
TI  - Management of acute kidney injury in cirrhosis.
AB  - Acute kidney injury (AKI) is a relatively frequent problem, occurring in
      approximately 20 % of hospitalized patients with cirrhosis. Although serum
      creatinine (S Cr) is the most commonly used method to determine AKI because of
      easy availability and low cost, practically it underestimates the extent of
      kidney injury in patients with chronic liver disease. AKI is defined as an abrupt
      rise in S Cr of 0.3 mg/dl or more (>26.4 mmol/l) or an increase of 150 % or more
      (1.5-fold) from baseline. The cause of AKI in cirrhosis is multifactorial and is
      unique in terms of pathogenesis. The most common causes of AKI in cirrhosis can
      be subdivided into either functional or structural. The functional group includes
      volume-responsive (prerenal azotemia) and volume-unresponsive states (hepatorenal
      syndrome). Volume responsive is the most common type of AKI due to frequent use
      of diuretics, large volume abdominal paracentesis and gastrointestinal bleeding
      in patients with liver disease. The structural causes include acute tubular
      necrosis, tubulointerstitial and glomerular diseases. Patients with decompensated
      cirrhosis are in a vasodilatory state leading to a decrease in effective arterial
      blood volume, predisposing to AKI. Therefore, management of AKI depends on the
      underlying cause, and therapy should be directed toward removal of the cause. The
      outcome in cirrhosis when patients are on dialysis is very dismal. Every effort
      should be made to prevent AKI. 

PMID- 26201920
TI  - A comparison of 4-year entecavir efficacy in nucleos(t)ide analog-naive and 
      experienced adult Taiwanese chronic hepatitis B patients.
AB  - PURPOSE: To compare the efficacy of entecavir (ETV) monotherapy up to 4 years in
      nucleos(t)ide analog (NA)-experienced and -naive subjects. METHODS: One hundred
      sixty NA-experienced and 282 naive chronic hepatitis B patients who were treated
      with ETV were enrolled. Of the 160 NA-experienced patients, 49 had prior
      lamivudine (LAM)-resistant mutants, 18 had resistant mutants to LAM followed by
      adefovir (ADV) after switching to ADV sequential therapy (LAM/ADV resistance),
      and 9 had prior ADV-resistant mutants. NA-resistant mutants were detected by line
      probe assay. RESULTS: Four years of ETV therapy resulted in virological response
      (VR, HBV DNA < 300 copies/ml), HBeAg seroconversion, and ETV-resistant mutants
      development in 98.2, 45.2, and <1 % of naive patients, respectively. LAM- and ADV
      experienced patients who never developed LAM-resistant mutants had similar VR and
      ETV-resistant mutant rates to NA-naive patients. In contrast, prior LAM-resistant
      mutants were significantly associated with higher ETV-resistant mutants
      development and reduced VR rates. Patients with prior LAM-resistant mutants but
      not at baseline had a lower rate of ETV-resistant mutants compared to those with
      baseline LAM-resistant mutants [hazard ratio (HR): 0.58, 95 % confidence interval
      (CI): 0.35-0.95] and those who had LAM/ADV resistance (HR:0.16, 95 % CI:1.0.03
      0.76). Early add-on ADV achieved VR in eight of nine patients with ETV-resistant
      mutants when HBV DNA was <2 * 10(5) copies/ml. CONCLUSIONS: Entecavir was highly
      efficacious and low resistance in NA-naive, LAM-, or ADV-experienced patients
      without LAM-resistant mutants. Patients with prior LAM-resistant mutants but not
      at baseline had lower ETV-resistant mutant rates compared to those with baseline
      LAM-resistant mutants or LAM/ADV resistance.

PMID- 26201919
TI  - Human genetic variation and the risk of hepatocellular carcinoma development.
AB  - Our understanding of the patho-physiology of hepatocellular carcinoma (HCC) is
      still much fragmented making difficult the improvement of the clinical outcome
      for the majority of HCC patients. Discovery of single nucleotide polymorphisms
      (SNPs) associated with individual susceptibility to HCC may enable the persons at
      risk to adapt their lifestyle and legitimate implementation by their doctors of
      surveillance programs facilitating early detection and subsequent management of
      the disease. To shed light on the influence of human genetic variation on HCC, we
      conducted a review of the meta-analyses of candidate SNPs and genome wide
      association studies (GWAS) performed for HCC by search of PubMed and Google
      Scholar databases. Genetic variations occurring in pathways historically
      considered as instrumental for liver tumorigenesis (TP53/MDM2, HLA, glutathione-S
      transferases/cytochrome P540, TNFalpha/TGFbeta, etc...) are discussed. An immense
      majority of the data has been produced in Eastern Asia (China, Japan, Korea).
      These meta-analyses indicate that the TP53, the MDM2 SNP309 G and the GSTT1 null
      genotype contribute to an increased risk of HCC both in Asians and Caucasians.
      Significant differences of odds ratios are, however, commonly observed between
      Eastern-Asians and other populations. Amazingly, GWAS studies performed so far
      exclusively with HCC patients from Eastern Asia produced drastically different
      outcomes pointing at unrelated biological pathways. The small magnitude of the
      risk associated with the genetic variants raises the question of their future
      utility as markers in clinical practice. An assessment of their impact on tumor
      progression (vascular invasion, metastases) remains, however, to be done and may
      prove to be more useful for clinicians. Finally, the evaluation of these variants
      is not available for various populations of the world and particularly for
      Subsaharan Africans who are especially affected by HCC. 

PMID- 26201921
TI  - Downregulation of TIPE2 mRNA expression in peripheral blood mononuclear cells
      from patients with chronic hepatitis C.
AB  - PURPOSE: Hepatitis C virus (HCV) infection causes chronic hepatitis in
      approximately 80 % of cases. Although it is well recognized that the immune
      system plays an important role in determining the outcomes of HCV infection, the
      underlying molecular mechanisms of persistent HCV infection and hepatic injury
      are incompletely understood. Tumor necrosis factor-alpha-induced protein 8-like 2
      (TNFAIP8L2, TIPE2) is a newly identified negative regulator of innate and
      adaptive immunity. The goal of the present study is to investigate the potential
      role of TIPE2 in chronic hepatitis C (CHC) infection. METHODS: We used
      quantitative real-time reverse transcription polymerase chain reaction to examine
      the mRNA expression levels of TIPE2, Toll-like receptor (TLR) 2, and TLR4 in
      peripheral blood mononuclear cells from 60 CHC patients and 30 healthy controls.
      RESULTS: The TIPE2 mRNA expression was significantly downregulated, whereas that
      of TLR2 and TLR4 was upregulated in CHC patients compared with healthy controls.
      TIPE2 mRNA expression levels were negatively correlated with serum ALT, AST, and
      HCV RNA levels. TIPE2 mRNA expression was also negatively correlated with TLR2
      and TLR4 mRNA levels in CHC patients. Moreover, TIPE2 mRNA expression was
      upregulated, whereas that of TLR2 and TLR4 was downregulated after treatment of
      patients with interferon-alpha and ribavirin. CONCLUSIONS: These results indicate
      that HCV may promote chronic hepatitis by decreasing TIPE2 expression while
      enhancing TLR signaling.

PMID- 26201922
TI  - Three-dimensional magnetic resonance imaging for stringent diagnosis of advanced
      fibrosis associated with nonalcoholic steatohepatitis.
AB  - BACKGROUND: The definitive diagnosis of nonalcoholic steatohepatitis (NASH) is
      currently based on histopathological assessment. This study aimed to elucidate
      the utility of a novel noninvasive method, three-dimensional magnetic resonance
      imaging (3D-MRI), for diagnosing advanced fibrosis in patients with NASH, using
      histopathological diagnosis as the reference standard. METHODS: This
      retrospective study included 30 consecutive patients who had been diagnosed with
      NASH by histopathology and had undergone 3D-MRI before biopsy. 3D-MRI provided a
      three-dimensional reconstruction of the liver from contrast-enhanced
      hepatobiliary phase MR images. In the present study, histopathological advanced
      fibrosis was defined as stage 3 and 4 NASH. Advanced fibrosis, diagnosed by 3D
      MRI, was considered to be diffuse irregularity of the entire surface of the
      liver. The diagnostic features of 3D-MRI and the noninvasive evaluation systems
      (APRI, FIB-4 index, and BARD score) for identifying advanced and nonadvanced
      fibrosis of NASH were determined and compared. RESULTS: Nine (30 %) of the 30
      study patients were diagnosed histopathologically with advanced fibrosis, and 11
      (37 %) of 30 patients were diagnosed with advanced fibrosis using 3D-MRI. The
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) of 3D-MRI for diagnosing advanced fibrosis were 100, 90,
      82, and 100 %, respectively. The sensitivities of APRI, the FIB-4 index, and BARD
      score ranged from 78 to 89 %, the specificities from 71 to 90 %, the PPVs from 54
      to 78 %, and the NPVs from 88 to 94 %. CONCLUSION: Compared with the common
      noninvasive methods for diagnosing advanced fibrosis associated with NASH, 3D-MRI
      was more accurate.

PMID- 26201923
TI  - Roles of alcohol drinking pattern in fatty liver in Japanese women.
AB  - PURPOSE: Several studies have reported an inverse association between moderate
      alcohol consumption and prevalence of fatty liver (FL) in men. We aimed to
      clarify this association in women. METHODS: We collected health checkup data from
      4,921 Japanese women without concurrent liver disease (mean age 46.4 years) and
      performed a cross-sectional study to evaluate the influence of alcohol drinking
      patterns (frequency and amount) on the prevalence of FL as assessed by
      ultrasonography. RESULTS: Alcohol consumption was reported in 30.8 % of
      participants, and FL was observed in 13.8 % (15.5 % nondrinkers, 10.1 %
      drinkers). Alcohol consumption was inversely associated with FL prevalence
      [adjusted odds ratio (AOR) 0.79, 95 % confidence interval (CI) 0.63-0.98]. In
      analyses stratified by drinking frequency and/or amount of alcohol consumed, the
      risk of FL decreased for the following categories: 0.1-19.9 g/drinking day (AOR
      0.61, 95 % CI 0.44-0.83) and 0.1-69.9 g/week (AOR 0.74, 95 % CI 0.55-0.98). The
      amount of alcohol consumed directly correlated with the prevalence of FL in daily
      drinkers (p < 0.05), whereas there was no correlation between the frequency of
      alcohol consumption and FL prevalence. Alanine aminotransferase levels were
      significantly lower for the following categories: 0.1-19.9 g/drinking day for 1-3
      days a week (p = 0.016) and 0.1-69.9 g within 1-3 drinking days a week (p =
      0.004). CONCLUSIONS: Minimal alcohol consumption appears to have protective
      effects against nonalcoholic FL disease in women, although an increase in the
      amount of alcohol consumed appears to nullify the protective effect.

PMID- 26201924
TI  - Autoimmune hepatitis: the role of environmental risk factors: a population-based
      study.
AB  - PURPOSE: The etiology of autoimmune hepatitis (AIH) likely involves a complex
      interaction of genetic and environmental factors. We aim to investigate the
      associations between exposure to putative environmental factors and AIH and to
      quantify AIH risk in a first-degree relative. METHODS: We conducted a population
      based case-control study. Cases were AIH patients who were alive and resided in
      Canterbury, New Zealand, between 1 July 2011 and 30 June 2012. Controls were
      randomly selected from the Electoral Roll and were matched 2:1 to each case by
      age and gender. Self-reporting questionnaires that cover lifestyle factors,
      childhood factors and family history were used. RESULTS: 72 AIH cases and 144
      controls were included. We found that exposure to antibiotics within 12 months
      prior to AIH diagnosis (OR 12.98, 95 % CI 2.49-67.67, p < 0.01) was an
      independent risk factor for the development of AIH. Alcohol consumption (OR 0.43,
      95 % CI 0.28-0.68, p < 0.01) and childhood home with wood heating (OR 0.30, 95 %
      CI 0.14-0.63, p < 0.01) were independently associated with reduced risks of later
      development of AIH. The crude risk of AIH in first-degree relatives of a patient
      with AIH was 0.2 % (95 % CI <0.1-2.0). CONCLUSIONS: We found that antibiotics are
      an independent risk factor for the development of AIH, whereas alcohol
      consumption and living in a childhood home with wood heating are independent
      protective factors against the later development of AIH.

PMID- 26201925
TI  - Antioxidant status and GST gene polymorphisms in antitubercular treatment-induced
      hepatotoxicity patients.
AB  - INTRODUCTION: Hepatotoxicity is a serious adverse effect of antituberculosis
      treatment (ATT). Glutathione S-transferase (GST) is involved in the
      detoxification of toxic metabolites produced as a result of ATT, increased
      oxidative stress and decreased antioxidant levels, and differences in the GST
      polymorphism may be one of the causes of ATT-induced hepatotoxicity. AIM: This
      study was undertaken to study the relationship among antioxidant status,
      oxidative stress and GST gene polymorphisms in the development of ATT-induced
      hepatotoxicity in Indian patients. METHODOLOGY: Two hundred fifty TB patients
      attending clinics in the Gastroenterology and Thoracic Department, PGIMER,
      Chandigarh, were enrolled. Liver marker enzymes, markers of oxidative stress,
      levels of antioxidants and identification of GSTT1, GSTM1 and GSTP polymorphisms
      were performed using standard protocols. RESULTS: Of the 250 patients, 160 were
      males. Of the 160 males, 18 (11.3 %) had ATT-induced hepatotoxicity and 142 no
      hepatotoxicity, while of 90 females, 12 (13.3 %) had hepatotoxicity and 78 no
      hepatotoxicity. Patients who developed ATT-induced hepatotoxicity had
      significantly higher oxidative stress compared to those who did not develop
      hepatotoxicity at between 1 and 2 months of treatment. Among antioxidants,
      catalase did not show any significant difference at 2 and 4 months of treatment.
      The presence of GSTM1 was higher in hepatotoxicity patients as compared to non
      hepatotoxicity patients, while GSTT1 and GST1/M1 were lower. CONCLUSION:
      Therefore, in this study, the possible association of oxidative stress with ATT
      induced hepatotoxicity was observed. A role of the GST polymorphism in ATT
      induced hepatotoxicity was also found and thus could possibly identify the groups
      at highest risk of developing ATT-induced hepatotoxicity.

PMID- 26201926
TI  - Cytokines are associated with postembolization fever and survival in
      hepatocellular carcinoma patients receiving transcatheter arterial
      chemoembolization.
AB  - OBJECTIVE: Cytokines play important roles in angiogenesis, inflammation, and cell
      growth. The present study aimed to investigate the correlation between cytokine
      changes and clinical characteristics in hepatocellular carcinoma (HCC) patients
      receiving transcatheter arterial chemoembolization (TACE). METHODS: Forty-one
      TACE-naive HCC patients receiving 73 sessions of TACE and 30 healthy controls
      were studied. Serum levels of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor
      (VEGF), basic fibroblast growth factor (bFGF), angiogenin, epidermal growth
      factor (EGF), epidermal growth factor receptor, and transforming growth factor
      beta1 (TGF-beta1) before and at 1, 3, 5, 7, and 14 days after TACE as well as
      clinical parameters were analyzed. RESULTS: Baseline serum levels of VEGF, bFGF,
      IL-6, IL-8, and TNF-alpha in HCC patients were significantly elevated, whereas
      EGF and TGF-beta1 levels were lower compared to those in healthy controls (p <
      0.05 for all). Serum IL-6 increased rapidly and peaked on day 1 after TACE
      administration, whereas VEGF increased more slowly and peaked on day 14 after
      TACE administration. Patients with post-TACE fever had higher serum IL-6 levels
      on days 1, 3, and 5 (p < 0.005 for all). Patients with pre-TACE serum VEGF < 200
      pg/ml had a longer survival than those with pre-TACE serum VEGF levels >= 200
      pg/ml (22.2 months vs. 11.6 months, p = 0.014). Cox multivariate analysis showed
      that baseline serum VEGF significantly predicted survival for HCC patients
      receiving TACE. CONCLUSIONS: TACE is associated with the modulation of serum
      angiogenic, inflammatory, and cell growth cytokines in HCC patients. Serum IL-6
      correlates with post-TACE fever, and baseline serum VEGF independently predicts
      patient survival.

PMID- 26201927
TI  - Methylation profiling of serum DNA from hepatocellular carcinoma patients using
      an Infinium Human Methylation 450 BeadChip.
AB  - BACKGROUND: Alterations in DNA methylation frequently occur in hepatocellular
      cancer (HCC). The methylation status of circulating DNA might serve as a
      potential biomarker for cancers. METHODS: Six early stage HCC patients with
      chronic hepatitis B virus (HBV) infection and six age-matched healthy controls
      were selected for genome-scale DNA methylation screening of serum by Illumina
      Infinium Human Methylation 450 BeadChip. The chosen methylation sites were
      reassessed by bisulfite sequencing in four healthy controls and four early stage
      HCC patients with chronic HBV infection and were used for bead array screening.
      Another 27 healthy controls and 31 early stage HCC patients with chronic HBV
      infection were also chosen for further bisulfite sequencing validation. RESULTS:
      Whole-genome methylation was significantly lower in serum from HCC patients than
      in that from healthy controls. After bioinformatics analysis, methylation at DBX2
      and Thy-1 membrane glycoprotein (THY1) was reassessed by bisulfite sequencing.
      The correlation coefficients of DBX2 and THY1 between the Illumina 450 BeadChip
      and bisulfite sequencing were respectively 0.9145 and 0.8232. Twenty-seven
      healthy controls and 31 early stage HCC patients with chronic HBV infection were
      chosen for further validation. The diagnostic sensitivity and specificity of DBX2
      for differentiating healthy controls and early stage HCC were 88.89 and 87.10 %
      and of THY1 were 85.19 and 80.65 %. CONCLUSIONS: The results demonstrated that
      the 450K BeadChip is a useful tool for whole-genome serum DNA methylation
      screening of HCC, and some HCC-related DNA methylation sites were screened.

PMID- 26201928
TI  - The effects of intraoperative cryoprecipitate transfusion on acute renal failure
      following orthotropic liver transplantation.
AB  - PURPOSE: The definition of risk factors associated with acute renal failure (ARF)
      following orthotropic liver transplantation (OLT) is still controversial.
      Cryoprecipitate, which can supply fibrinogen and other coagulation factors, is
      widely used in OLT. However, the effects of intraoperative cryoprecipitate
      transfusion on ARF following OLT remain unclear. METHODS: In a series of 389
      adult patients who received grafts from deceased donors and underwent their first
      OLT, the clinical correlation between intraoperative cryoprecipitate transfusion
      and ARF following OLT was retrospectively studied after adjusting for potential
      confounders. The distribution of ARF and the causes of death within the first
      year after OLT were also compared separately in patients with and without
      cryoprecipitate transfusion. RESULTS: The incidence of ARF in patients with
      cryoprecipitate transfusion was significantly higher than in patients without
      cryoprecipitate transfusion (15.9 vs. 7.8 %, p = 0.012). A nonlinear relationship
      between intraoperative cryoprecipitate transfusion and ARF following OLT was
      observed. The risk of ARF increased with the cryoprecipitate transfusion level up
      to the turning point (16 U) (adjusted OR 1.1, 95 % CI 1.1-1.2; p < 0.001). When
      the cryoprecipitate level exceeded 16 U, the level of cryoprecipitate transfusion
      was not associated with the risk of ARF (OR 0.95, 95 % CI 0.85-1.1; p = 0.319).
      Deaths within the first year after the operation occurred more frequently in
      cases with cryoprecipitate transfusion (22.9 vs. 14.2 %, p = 0.029). CONCLUSIONS:
      These findings suggested that intraoperative cryoprecipitate transfusion is
      associated with ARF following OLT. Cryoprecipitate transfusion during OLT should
      be performed carefully until more convincing evidence has been found.

PMID- 26201929
TI  - Liver transplantation for iatrogenic bile duct injuries sustained during
      cholecystectomy.
AB  - PURPOSE: The aim of this study was to report a single-center experience and
      review the literature on liver transplantation (LT) for iatrogenic bile duct
      injury (BDI) sustained during cholecystectomy. METHODS: A retrospective review of
      a prospectively maintained database of LT between 1990 and December 2012 was
      performed. For the same period, a review of the literature on LT for BDI was
      undertaken. RESULTS: Six patients, with a mean age of 55.3 years (range 52-65),
      referred at a mean interval of 206 months (range 96-384) from BDI underwent LT.
      All patients had class E Strasberg BDIs and were referred with end-stage liver
      disease after multiple previous attempts at BDI repairs. Mortality, morbidity,
      and retransplantation rates were 16.6, 50, and 16.6 %, respectively. Five
      patients were alive at a mean follow-up time of 80.4 +/- 92 months. Fifty-eight
      patients listed or transplanted for BDI were identified and reviewed. Indications
      for LT included chronic or acute liver failure (22.4 %) and the delay between BDI
      and referral for LT ranged from 1 day to 180 months. Associated vascular injuries
      were present in 41.3 % of the patients, and 72.4 % of the patients had previous
      failed BDI repairs. The overall postoperative mortality was 34.4 %, and the
      morbidity ranged from 60 to 100 %. The overall 5-year survival reached 75 %.
      CONCLUSIONS: A long interval of time between BDI and referral to tertiary centers
      for repair, a high rate of associated vascular injuries, and multiple failed
      previous repair attempts characterize the clinical history of patients undergoing
      LT for BDI. Operative morbidity and mortality rates of LT in the setting of BDI
      are particularly high for patients with bilio-vascular injuries presenting with
      acute liver failure and for patients with chronic liver disease due to multiple
      previous repair attempts and recurrent preoperative biliary infection.

PMID- 26201930
TI  - Cytokine gene polymorphisms in acute cellular rejection following living donor
      liver transplantation: analysis of 155 donor-recipient pairs.
AB  - PURPOSE: Despite improvements in immunosuppressive therapy, acute cellular
      rejection (ACR) remains an important cause of graft loss in patients undergoing
      liver transplantation. Recently, associations between cytokine gene polymorphisms
      in recipients and the occurrence of ACR have been reported. However, most studies
      did not investigate gene polymorphisms in donors or were limited by the number of
      cases investigated. METHODS: We examined 155 living donor liver transplantation
      (LDLT) patients treated at Nagoya University or Kyoto University from 2004 to
      2009. The following gene polymorphisms in recipients and donors were analyzed:
      tumor necrosis factor A (TNF-A) T-1031C, interleukin 2 (IL-2) T-330G, IL-10C
      819T, IL-13C-1111T, and transforming growth factor B (TGF-B) T29C. RESULTS: Forty
      seven recipients (30.3 %) developed early ACR. Of the investigated gene
      polymorphisms, the IL-13 -1111C/C genotype in recipients was significantly
      associated with a higher incidence of ACR relative to the other two genotypes (OR
      = 2.64, 95 % CI 1.19-5.86, p = 0.017), while we showed the lack of association
      between investigated gene polymorphisms in donors and ACR incidence. CONCLUSION:
      The IL-13 -1111C/C genotype in recipients might be a risk factor for ACR in LDLT,
      and this might contribute to individualized immunosuppression strategies for
      recipients. On the other hand, the current study showed no associations of
      cytokine gene polymorphisms in donors with ACR incidence.

PMID- 26201931
TI  - Dopamine from cirrhotic liver contributes to the impaired learning and memory
      ability of hippocampus in minimal hepatic encephalopathy.
AB  - Background Defective learning/memory ability is a feature of MHE. However, the
      exact pathophysiological mechanisms leading to the impairment of learning/memory
      ability in MHE remain not clearly understood. Methods MHE rat modeling by
      intraperitoneal injection of TAA was successfully established using a Morris
      water maze, BAEP, and EEG tests. COMT inhibitor, a protein involved in the
      accumulation of dopamine (DA), was found to be up-regulated in cirrhotic livers
      in MHE by 2-DE/MS. Results The levels of DA in cirrhotic livers, serums and
      hippocampuses in the MHE group were more significantly increased than in the
      control group. In the hippocampuses of MHE rats, NMDA-induced formation of cGMP
      was reduced by 40 % as determined by in vivo brain microdialysis. Activation of
      sGC by NO was reduced by 38 %. The expression of NMDAR1, CaM, nNOS and sGC in the
      hippocampus in the MHE group were more significantly decreased than in controls.
      Chronic exposure of cultured hippocampus neurons to DA (50 MUM) reduced by 53 %
      the NMDA-induced formation of cGMP. Activation of sGC by NO in these neurons was
      reduced by 44 %. Down-regulated NMDAR1, CaM, nNOS and sGC were also detected in
      neurons treated with dopamine, in contrast with the controls. Conclusions This
      study suggests that when the glutamate-NO-cGMP pathway in the hippocampus is
      inhibited by the elevation of DA from cirrhotic livers, this in turn may lead to
      the impairment of learning and memory ability of MHE. 

PMID- 26201932
TI  - Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined
      transcriptional factors.
AB  - PURPOSE: Liver transplantation is currently the only curative therapeutic option
      for end-stage liver cirrhosis. However, due to the limitations of donor liver
      availability and occasional rejection, it cannot always be successfully applied.
      In this study, we determined whether fibroblasts can be transdifferentiated into
      hepatocyte-like cells by transcription factors that initiate and maintain
      hepatocyte differentiation. METHODS: Fibroblasts were transduced with retrovirus
      vectors carrying FOXA2, HNF4alpha, and C/EBPbeta. To enhance the efficiency of
      transdifferentiation, cMyc was also expressed. RESULTS: Transdifferentiation was
      successful using both neonatal fibroblasts and human forehead fibroblasts. The
      transdifferentiated cells produced hepatocyte-specific proteins such as albumin
      and cytochrome, and had important hepatocyte-specific functions, such as glycogen
      storage and indocyanine green uptake, suggesting that the cells function at least
      as partial hepatocytes. CONCLUSIONS: These results provide a novel method of
      generating differentiated hepatocyte-like cells, and may represent an alternative
      source of cells for future cell-based therapeutics for end-stage liver diseases.

PMID- 26201933
TI  - Copper Environment in Artificial Metalloproteins Probed by Electron Paramagnetic
      Resonance Spectroscopy.
AB  - The design of binding sites for divalent metals in artificial proteins is a
      productive platform for examining the characteristics of metal-ligand
      interactions. In this report, we investigate the spectroscopic properties of
      small peptides and four-helix bundles that bind Cu(II). Three small peptides,
      consisting of 15 amino acid residues, were designed to have two arms, each
      containing a metal-binding site comprised of different combinations of imidazole
      and carboxylate side chains. Two four-helix bundles each had a binding site for a
      central dinuclear metal cofactor, with one design incorporating additional
      potential metal ligands at two identical sites. The small peptides displayed pH
      dependent, metal-induced changes in the circular dichroism spectra, consistent
      with large changes in the secondary structure upon metal binding, while the
      spectra of the four-helix bundles showed a predominant alpha-helix content but
      only small structural changes upon metal binding. Electron paramagnetic resonance
      spectra were measured at X-band revealing classic Cu(II) axial patterns with
      hyperfine coupling peaks for the small peptides and four-helix bundles exhibiting
      a range of values that were related to the specific chemical natures of the
      ligands. The variety of electronic structures allow us to define the distinctive
      environment of each metal-binding site in these artificial systems, including the
      designed additional binding sites in one of the four-helix bundles. 

PMID- 26201935
TI  - The outcome and the frequency of pathological complete response after neoadjuvant
      radiotherapy in curative resections for advanced rectal cancer: a population
      based study.
AB  - AIM: Pathological complete response (ypCR) after neoadjuvant treatment for rectal
      cancer is associated with favourable survival and a low rate of local recurrence.
      The aim of the study was to assess the incidence of ypCR among patients with
      advanced rectal cancer treated with neoadjuvant chemoradiotherapy and curative
      resection and to explore factors associated with survival. METHOD: From 2000 to
      2009, 1384 patients enrolled in the national population- based colorectal cancer
      registry of Norway with advanced T3 and T4 rectal cancer with N0-2, M0 received
      neoadjuvant long-course (chemo)radiation. The duration of follow-up was a median
      of 5 years. RESULTS: ypCR was achieved in 147 (10.6%) patients. The estimated 5
      year overall survival rate was 87% (confidence interval +/- 5.4) among ypCR and
      67% among non-ypCR (confidence interval +/- 2.7) (P < 0.0001). Distant metastasis
      developed in 12 (8%) of 147 and 328 (26.5%) of 1237 patients respectively (P <
      0.001). In a Cox proportional hazards ratio model the effect of ypCR on survival
      was adjusted for age [hazard ratio (HR) 1.056, P = 0.0001], metachronous
      metastasis (HR 4.7, P = 0.0001), local recurrence (HR 4.3, P = 0.0001) and
      surgical procedure (HR 1.48, P = 0.0001). The independent effect of ypCR (HR
      0.65, P = 0.041) on survival almost disappeared compared with the univariate
      analysis. CONCLUSION: The rate of ypCR in advanced rectal cancer was about 10%.
      This phenomenon seems to occur in tumours with a low risk of metastasizing. The
      contribution of neoadjuvant therapy to ypCR on survival was small or absent.

PMID- 26201934
TI  - Naso-jejunal fluid resuscitation in predicted severe acute pancreatitis:
      Randomized comparative study with intravenous Ringer's lactate.
AB  - INTRODUCTION: Early management of severe acute pancreatitis (SAP) includes
      intravenous fluid resuscitation. AIM: To confirm feasibility of naso-jejunal (NJ)
      fluid resuscitation using oral hydration solution (ORS) and compare its efficacy
      with intravenous (IV) fluid resuscitation using Ringer Lactate (RL) in predicted
      SAP. PATIENTS AND METHODS: All patients of predicted SAP (presence of SIRS or
      BISAP > 2) without significant co morbidities were randomized to NJ group (ORS:
      20 ml/kg bolus and then 3 mL/kg/h) or IV group (RL infusion at same rate). The
      groups were compared vis-a-vis persistent organ failure (POF), pancreatic
      necrosis, and mortality. RESULTS: Seventy-seven patients were assessed and after
      exclusion, 49 patients were randomized to either NJ (24 patients) or IV group
      (25). The demographic and baseline clinical profile of both groups including
      BISAP score (2.25 +/- 0.73 and 2.32 +/- 0.56), hematocrit (40.2 +/- 6.8 and 38.3
      +/- 6.6), blood urea nitrogen (16.88 +/- 6.69 and 21.44 +/- 17.56 mg/dL), and
      intra-abdominal pressure (14.55 +/- 4.8 and 14.76 +/- 5.5 cm of water) were
      similar. NJ resuscitation had to be stopped in two patients because of abdominal
      discomfort and distension. The change in intra abdominal pressure after 48 h of
      hydration was comparable in both groups. The occurrence of POF (66.67% and 68%),
      pancreatic necrosis (69.5% and 76%), intervention (5 each), surgery (1 each), and
      mortality (16.5% and 8%) were comparable (P > 0.05). CONCLUSION: In select group
      of patients with SAP, NJ fluid resuscitation with ORS is feasible and is equally
      efficacious as IV fluid resuscitation with RL.

PMID- 26201936
TI  - The Impact of an Increase in User Costs on the Demand for Emergency Services: The
      Case of Portuguese Hospitals.
AB  - Evidence on the impact of user costs on healthcare demand in 'universal' public
      National Health Services (NHS) is scarce. The changes in copayments and in the
      regulation of the provision of free patient transportation, introduced in early
      2012 in Portugal, provide a natural experiment to evaluate that impact. However,
      those changes in user costs were accompanied with changes in the criteria that
      determine which patients are exempt from copayments, implying that simple
      comparisons of user rates would be biased. In this paper, we develop a new
      methodology to evaluate the impact of increases in direct and indirect user costs
      on the demand for emergency services (ES) in the presence of compositional
      changes in co-payment exempt and non-exempt populations. Our results show that
      the increase in copayments did not have an effect in moderating ES demand by
      paying users, but we find significant effects of the change in transport
      regulation. Thus, our results support the conclusion that indirect costs may be
      more important than direct costs in determining healthcare demand in NHS
      countries where copayments are small and wide exemption schemes are in place,
      especially for older patients. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26201937
TI  - Nonalcoholic fatty pancreas disease and Nonalcoholic fatty liver disease: more
      than ectopic fat.
AB  - OBJECTIVE: The aim of this study was to evaluate the metabolic effects of fatty
      pancreas (nonalcoholic fatty pancreas disease - NAFPD) in a group of obese
      paediatric patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We
      included 121 consecutive children with echographic evidence of hepatic steatosis.
      All patients underwent to abdominal ultrasound to evaluate pancreatic echogenic
      pattern. We divided the patients into two groups on the basis of the presence of
      fatty pancreas. In all patients liver function tests, lipid and gluco-insulinemic
      profile were evaluated. A selected subset of patients (67) underwent to liver
      biopsy. RESULTS: Of these 121 patients, 58 showed NAFPD and 63 patients exhibited
      a normal pancreatic echogenic pattern. No differences were found in age,
      transaminases serum levels, lipid profile and pancreatic enzymes between the two
      groups. The patients with NAFPD had a significantly higher z-BMI, fasting
      insulin, insulin resistance (HOMA-IR) and lower ISI respect to the group without
      fatty pancreas. The patients with fatty pancreas showed a more advanced form of
      liver disease, with higher values of fibrosis, ballooning and NAS score with
      respect to the group without NAFPD. CONCLUSIONS: Our study demonstrated that
      NAFPD is a frequent condition in obese paediatric patients affected by NAFLD. Our
      data suggest that pancreatic fat should not be considered an inert accumulation
      of fat, but as an additional factor able to affect glucose metabolism and
      severity of liver disease, increasing the risk of develop metabolic syndrome.

PMID- 26201938
TI  - Immunosuppressive activity of cancer-associated fibroblasts in head and neck
      squamous cell carcinoma.
AB  - Cancer-associated fibroblasts (CAFs) have been shown to play an important role in
      angiogenesis, invasion, and metastasis. In the present study, we determined
      whether CAFs within the tumor microenvironment (TME) in head and neck squamous
      cell carcinoma (HNSCC) contributed to promoting immunosuppression and evasion
      from immune surveillance. Six pairs of CAFs and normal fibroblasts (NFs) were
      established from the resected tumor tissues of patients with HNSCC. The effects
      of CAFs and NFs on the functions of T cells were comparatively analyzed. CAFs
      expressed the co-regulatory molecules, B7H1 and B7DC, whereas NFs did not. The
      expression levels of cytokine genes, including those for IL6, CXCL8, TNF, TGFB1,
      and VEGFA, were higher in CAFs. T cell proliferation was suppressed more by CAFs
      or their supernatants than by NFs. Moreover, PBMCs co-cultured with the
      supernatants of CAFs preferentially induced T cell apoptosis and regulatory T
      cells over those co-cultured with the supernatants of NFs. A microarray analysis
      revealed that the level of genes related to the leukocyte extravasation and
      paxillin signaling pathways was higher in CAFs than in NFs. These results
      demonstrated that CAFs collaborated with tumor cells in the TME to establish an
      immunosuppressive network that facilitated tumor evasion from immunological
      destruction.

PMID- 26201939
TI  - Application of Chan-Lam cross coupling for the synthesis of N-heterocyclic
      carbene precursors bearing strong electron donating or withdrawing groups.
AB  - Chan-Lam cross coupling allowed efficient synthesis of N,N'-disubstituted ortho
      phenylene diamines bearing strong electron donating or withdrawing groups, such
      as nitro or methoxy groups, with moderate to high yields. These diamines can then
      be turned into N-heterocyclic carbene precursors after condensation with
      trimethyl orthoformate. The same strategy can also be utilized for the synthesis
      of N-monosubstituted aniline derivatives containing a functionalized ortho
      aminomethyl group as intermediates for chiral 6-membered ring carbene precursors.

PMID- 26201941
TI  - The meaning of a high plasma free haemoglobin: retrospective review of the
      prevalence of haemolysis and circuit thrombosis in an adult ECMO centre over 5
      years.
AB  - AIMS: In adults requiring extracorporeal membrane oxygenation (ECMO), we wanted
      to determine; i) the frequency of elevated plasma free haemoglobin (PFHb), ii)
      the reasons for circuit changes and iii) whether elevated PFHb was associated
      with higher in-hospital mortality. MATERIALS AND METHODS: Patients requiring ECMO
      between January 2010 and August 2014 were identified from a prospectively
      collected ECMO database. Their scanned medical records and pathology results were
      reviewed. Relevant patient, biochemical and circuit data were collected on an
      Excel spreadsheet and analysed using Stata 13 (StataCorp, College Station, TX).
      The patients were analysed in three groups, depending on their peak PFHb during
      ECMO: 'Normal PFHb' (<0.1 g/L), 'Low level PFHb' (0.1 - 0.5 g/L), 'High level
      PFHb' (>0.5 g/L). MAIN RESULTS: There were 184 ECMO runs (56 VV, 128 VA) - 61
      'Normal PFHb', 99 'Low level PFHb', 24 'High level PFHb'. Circuit thrombosis
      (pump, oxygenator) or haemolysis requiring exchanges were significantly more
      common in VV ECMO compared to VA ECMO - 23.21% (13/56) vs. 0.78% (1/128),
      p<0.001. Elevated PFHb was associated with a longer duration of haemofiltration
      (p<0.001) and ECMO support (p<0.001). In-hospital mortality rates for the 'Normal
      PFHb', 'Low level PFHb' and 'High level PFHb' groups were 16.39% (10/61), 30.30%
      (30/99) and 37.50% (9/24), respectively, p=0.067. CONCLUSION: Elevated PFHb
      values during adult ECMO were common. Severe haemolysis or thrombosis requiring
      circuit changes were uncommon and occurred almost exclusively on VV ECMO. There
      was a non-statistically significant increase in in-hospital mortality with
      elevated PFHb and studies of larger registry data may clarify the prognostic
      value of PFHb in adult patients.

PMID- 26201942
TI  - Prospective multicentre cohort study of patient-reported outcomes after
      cholecystectomy for uncomplicated symptomatic cholecystolithiasis.
AB  - BACKGROUND: Up to 33 per cent of patients with uncomplicated symptomatic
      cholecystolithiasis report persistent pain after cholecystectomy. The aim of this
      study was to determine characteristics associated with patient-reported absence
      of abdominal pain after cholecystectomy, improved abdominal symptoms, and patient
      reported positive cholecystectomy results in a prospective cohort multicentre
      study. METHODS: Patients aged 18 years or more with symptomatic
      cholecystolithiasis who had a cholecystectomy between June 2012 and June 2014 in
      one of three hospitals were included. Before surgery all patients were sent the
      Gastrointestinal Quality of Life Index (GIQLI) questionnaire and the McGill Pain
      Questionnaire (MPQ). At 12 weeks after surgery, patients were invited to complete
      the GIQLI and Patients' Experience of Surgery Questionnaire (PESQ). Logistic
      regression analyses were performed to determine associations. RESULTS:
      Questionnaires were sent to 552 patients and returned by 342 before and after
      surgery. Postoperative absence of abdominal pain was reported by 60.5 per cent of
      patients. A high preoperative GIQLI score, episodic pain, and duration of pain of
      1 year or less were associated with postoperative absence of pain. These factors
      showed no association with improved abdominal symptoms (reported by 91.5 per cent
      of patients) or a positive surgery result (reported by 92.4 per cent).
      CONCLUSION: Preoperative characteristics determine the odds for relief of
      abdominal pain after cholecystectomy. However, these factors were not associated
      with patient-reported improvement of abdominal symptoms or patient-reported
      positive cholecystectomy results, highlighting the variation of internal
      standards and expectations of patients before cholecystectomy.

PMID- 26201943
TI  - Bone involvement in males with Kallmann disease.
AB  - BACKGROUND: Kallmann syndrome (KS) is a rare genetic condition characterized by
      congenital early-onset hypogonadotropic hypogonadism and anosmia or hyposmia.
      Male subjects are more frequently affected and present absent/delayed puberty,
      low testosterone levels with higher risk for osteoporosis. Therefore, to maintain
      normal levels of sex steroids and prevent bone loss, male KS needs life-long
      hormonal replacement therapy (HRT). AIMS: The objective of our study is to assess
      bone involvement in subjects with KS currently treated with HRT. METHODS: In our
      retrospective study, we analyzed data from medical records of patients with KS
      treated with HRT (either gonadotropins or testosterone preparations), including
      clinical history, biochemical parameters, and the following outcome measures: the
      bone mineral density (BMD) at the lumbar spine (LS), femoral neck (FN), and total
      body less head (TBLH); and the Vertebral Fracture Assessment (VFA) by Dual Energy
      X-ray Absorptiometry (DXA). RESULTS: Clinical and instrumental data of 32
      patients with KS were evaluated; their mean age was 30.32 (+/- 10.09) years,
      their mean body mass index (BMI) was 25.71 (+/- 3.23) kg/m(2). Four patients
      (12.5%) had a LS BMD Z score below the expected range for age. Five patients had
      vertebral deformities observed at VFA. Duration of HRT was related to bone health
      parameters: BMD at all measured sites were higher in patients receiving adequate
      HRT for more than 2 years compared with the patients treated for less than 6
      months. A deficient vitamin D status was found in 43% of cases and it was
      prevalent in patients with shorter HRT. DISCUSSION AND CONCLUSION: Early starting
      and adequate duration of HRT are related to bone health parameters in patients
      with congenital hypogonadotropic hypogonadism due to KS. Restoring vitamin D
      sufficiency might also be advisable in this condition.

PMID- 26201944
TI  - [Vitamin D metabolism of the bone].
AB  - BACKGROUND: Bone health is a crucial requirement for individual mobility.
      Preventive, diagnostic, and therapeutic actions to preserve or restore bone
      health are major tasks for orthopedic surgeons and health practitioners in
      musculoskeletal medicine. RESULTS: In the context of the widespread vitamin D
      deficiency in Germany, it is relevant to keep in mind thatserum calcitriol levels
      above > 30 ug/l are necessary for optimal bone metabolism and bone health. In
      particular, because vitamin D deficiency not only increases the amount of non
      mineralized bone matrix (osteoid), but it can also cause negative changes in the
      mineralized bone tissue. Widening of the osteons and osteocyte lacunae, together
      with increased bone aging under the osteoid layer, can lead to reduced fracture
      resistance. CONCLUSION: Integration of bone metabolism into the orthopedic
      strategy is an important concept for optimizing treatment in modern
      musculoskeletal medicine.

PMID- 26201945
TI  - [Glomuvenous malformations].
AB  - SYMPTOMS: A patient presented suffering from neural pain in the medial foot for a
      period of over 20 years. DIAGNOSIS: Diagnostic showed a widely spread soft-tissue
      tumor consisting of confluent glomuvenous malformations that was responsible for
      the immense pain syndrome.The solitary or multiform-appearing knots are not
      compressible and manifest as the characteristic syndromes of regional pain,
      sensitivity to coldness, or local pressure pain. Alternatively, the patient could
      also be completely symptom-free. TREATMENT: Because of the dimension of the tumor
      and the degree of suffering, a radical resection with simultaneous microsurgical
      reconstruction was carried out. Twelve weeks postoperatively, healing of the flap
      stabilized, the foot is fully weight-bearing, and the patient is pain-free.

PMID- 26201946
TI  - Evolution of bone disease after kidney transplantation: A prospective
      histomorphometric analysis of trabecular and cortical bone.
AB  - AIM: Post-transplant bone disease results from multiple factors, including
      previous bone and mineral metabolism disturbances and effects from transplant
      related medications. Bone biopsy remains the gold-standard diagnostic tool.
      METHODS: We aimed to prospectively evaluate trabecular and cortical bone by
      histomorphometry after kidney transplantation. Seven patients, willing to perform
      follow-up bone biopsy, were included in the study. Dual-X-ray absorptiometry and
      trans-iliac bone biopsy were performed within the first 2 months after renal
      transplantation and repeated after 2-5 years of follow-up. RESULTS: Follow-up
      biopsy revealed a significant decrease in osteoblast surface/bone surface (0.91
      +/- 0.81 to 0.47 +/- 0.12%, P = 0.036), osteoblasts number/bone surface (0.45
      (0.23, 0.94) to 0.00/mm(2) , P = 0.018) and erosion surface/bone surface (3.75 +/
      2.02 to 2.22 +/- 1.38%, P = 0.044). A decrease in trabecular number (3.55 (1.81,
      2.89) to 1.55/mm (1.24, 2.06), P = 0.018) and increase in trabecular separation
      (351.65 +/- 135.04 to 541.79 +/- 151.91 MUm, P = 0.024) in follow-up biopsy
      suggest loss in bone quantity. We found no significant differences in cortical
      analysis, except a reduction in external cortical osteonal eroded surface (5.76
      (2.94, 13.97) to 3.29% (0.00, 6.67), P = 0.043). Correlations between bone
      histomorphometric and dual-X-ray absorptiometry parameters gave inconsistent
      results. CONCLUSIONS: The results show a reduction in bone activity, suggesting
      increased risk of adynamic bone and loss of bone volume. Cortical bone seems less
      affected by post-transplant biological changes in the first years after kidney
      transplantation.

PMID- 26201947
TI  - Androgen Receptor Coactivators in Regulation of Growth and Differentiation in
      Prostate Cancer.
AB  - Androgen receptor (AR) is a key factor in regulation of growth and
      differentiation in normal and malignant prostate. Endocrine therapies for
      prostate cancer include inhibition of androgen production either by analogs of
      luteinizing hormone releasing hormone or abiraterone acetate and/or use of anti
      androgens such as hydroxyflutamide, bicalutamide, and enzalutamide. Castration
      therapy-resistant cancer develops inevitably in patients who undergo treatment.
      AR coactivators are proteins which interact with one or more regions of the AR
      thus enhancing its function. Although several functions of AR coactivators may be
      redundant, specific functions have been identified and analyzed. The p160 group
      of coactivators, SRC-1, -2, and -3 not only potentiate the activation of the AR,
      but are also implicated in potentiation of function of insulin-like growth factor
      I and activation of the Akt pathway. Transcriptional integrators p300 and CBP are
      up-regulated by androgen ablation and may influence antagonist/agonist balance of
      non-steroidal anti-androgens. A therapy approach designed to target p300 in
      prostate cancer revealed its role in regulation of proliferation of migration of
      androgen-sensitive and -insensitive prostate cancer cells. Coactivators p300 and
      SRC-1 are required for AR activation by interleukin-6 (IL-6), a cytokine that is
      overexpressed in castration therapy-resistant prostate cancer. Some coactivators,
      such as Vav3, are involved in regulation of transcriptional activity of truncated
      AR, which emerge during endocrine thrapy. Stimulation of cellular migration and
      invasion by AR coactivators has also been described. Translational studies with
      aim to introduce anti-AR coactivator therapy have not been successfully
      implemented in the clinic so far.

PMID- 26201948
TI  - Methodological Challenges When Comparing Demographic and Clinical Characteristics
      of International Observational Registries.
AB  - OBJECTIVE: Comparisons of data from different registries can be helpful in
      understanding variations in many aspects of rheumatoid arthritis (RA). The study
      aim was to assess and improve the comparability of demographic, clinical, and
      comorbidity data from 5 international RA registries. METHODS: Using predefined
      definitions, 2 subsets of patients (main cohort and subcohort) from 5
      international observational registries (Consortium of Rheumatology Researchers of
      North America Registry [CORRONA], the Swedish Rheumatology Quality of Care
      Register [SRR], the Norfolk Arthritis Register [NOAR], the Institute of
      Rheumatology Rheumatoid Arthritis cohort [IORRA], and CORRONA International) were
      evaluated and compared. Patients ages >18 years with RA, and present in or
      recruited to the registry from January 1, 2000, were included in the main cohort.
      Patients from the main cohort with positive rheumatoid factor and/or erosive RA
      who had received >=1 synthetic disease-modifying antirheumatic drug (DMARD), and
      switched to or added another DMARD, were included in the subcohort at time of
      treatment switch. RESULTS: Age and sex distributions were fairly similar across
      the registries. The percentage of patients with a high Disease Activity Score in
      28 joints score varied between main cohorts (17.5% IORRA, 18.9% CORRONA, 24.7%
      NOAR, 27.7% CORRONA International, and 36.8% SRR), with IORRA, CORRONA, and
      CORRONA International including more prevalent cases of RA; the differences were
      smaller for the subcohort. Prevalence of comorbidities varied across registries
      (e.g., coronary artery disease ranged from 1.5% in IORRA to 7.9% in SRR), partly
      due to the way comorbidity data were captured and general cultural differences;
      the pattern was similar for the subcohorts. CONCLUSION: Despite different
      inclusion criteria for the individual RA registries, it is possible to improve
      the comparability and interpretability of differences across RA registries by
      applying well-defined cohort definitions.

PMID- 26201949
TI  - Needle detachment in a slim and physically active child with insulin pump
      treatment.
AB  - Insulin pump therapy (CSII) is well established in pediatric patients with type 1
      diabetes. In childhood diabetes, insulin pump treatment shows considerable
      advantages such as fewer injections, increased flexibility, fewer hypoglycemic
      events and lower HbA1c levels. Side effects such as catheter obstruction,
      technical pump failure, and dermatological complications have been observed, but
      are rarely reported. The reported patient is a physically very active and slim 10
      year-old boy with reduced subcutaneous fatty tissue. After strong muscular
      activity an accidental rupture of the infusion set and needle detachment occurred
      in October 2013. X-ray and ultrasound imaging localized the needle in the
      musculus rectus femoris dexter. The needle was kept in situ and oral antibiotic
      treatment to prevent inflammatory reaction was prescribed. Repeated ultrasound
      measurements documented that the needles position had remained unchanged. Steel
      needle catheters (Sure-T infusion set, 6 mm) positioned in a thin layer of
      subcutaneous fat tissue of the thigh, combined with intense sports activity can
      result in a needle rupture and penetration into the muscle. Careful monitoring
      provides an alternative to surgery and lowers the risk of muscular necrosis.
      Because of differences in the distribution of subcutaneous fat tissue, an
      individualized catheter selection is necessary in pump treatment for children and
      adolescents, requiring a variety of different catheter sets.

PMID- 26201950
TI  - Nerve ultrasound identifies abnormalities in the posterior interosseous nerve in
      patients with proximal radial neuropathies.
AB  - INTRODUCTION: The radial nerve and posterior interosseous nerve (PIN) are prone
      to injury at multiple sites. Electrodiagnostic (EDx) studies may only identify
      the most proximal lesion. Nerve ultrasound could augment EDx by visualizing
      additional pathology. METHODS: This investigation was a retrospective examination
      of ultrasound and EDx from 26 patients evaluated for posterior cord/radial/PIN
      lesions. RESULTS: Eighteen of 26 patients had abnormalities on EDx (15 radial, 2
      PIN, 1 posterior cord). Ultrasound identified 15 of 18 (83%) of the EDx
      abnormalities and provided additional diagnostic information. In 6 of 15 (40%)
      patients with EDx evidence of radial neuropathy, ultrasound identified both
      radial nerve enlargement and additional, unsuspected PIN enlargement (53% to 339%
      enlarged vs. unaffected side). Ultrasound also identified: nerve (dis)continuity
      at the trauma site (n = 8); and nerve tumor (n = 2; 1 with normal EDx).
      CONCLUSION: In radial neuropathy, ultrasound often augments EDx studies and
      identifies a second lesion in the PIN. Further studies are required to determine
      the etiology and significance of this additional distal pathology.

PMID- 26201951
TI  - A novel monoclonal antibody to a defined peptide epitope in MUC16.
AB  - The MUC16 mucin is overexpressed and aberrantly glycosylated in ovarian
      carcinomas. Immunodetection of circulating MUC16 is one of the most used cancer
      biomarker assays, but existing antibodies to MUC16 fail to distinguish normal and
      aberrant cancer glycoforms. Although all antibodies react with the tandem-repeat
      region, their epitopes appear to be conformational dependent and not definable by
      a short peptide. Aberrant glycoforms of MUC16 may constitute promising targets
      for diagnostic and immunotherapeutic intervention, and it is important to develop
      well-defined immunogens for induction of potent MUC16 immunity. Here, we
      developed a MUC16 vaccine based on a 1.7TR (264 aa) expressed in Escherichia coli
      and in vitro enzymatically glycosylated to generate the aberrant cancer
      associated glycoform Tn. This vaccine elicited a potent serum IgG response in
      mice and we identified two major immunodominant linear peptide epitopes within
      the tandem repeat. We developed one monoclonal antibody, 5E11, reactive with a
      minimum epitope with the sequence FNTTER. This sequence contains potential N- and
      O-glycosylation sites and, interestingly, glycosylation blocked binding of 5E11.
      In immunochemistry of ovarian benign and cancer lesions, 5E11 showed similar
      reactivity as traditional MUC16 antibodies, suggesting that the epitope is not
      efficiently glycosylated. The study provides a vaccine design and immunodominant
      MUC16 TR epitopes. 

PMID- 26201953
TI  - MicroRNAs and PARP: co-conspirators with ROS in pulmonary hypertension. Focus on
      "miR-223 reverses experimental pulmonary arterial hypertension".

PMID- 26201952
TI  - Estimating the magnitude of near-membrane PDE4 activity in living cells.
AB  - Recent studies have demonstrated that functionally discrete pools of
      phosphodiesterase (PDE) activity regulate distinct cellular functions. While the
      importance of localized pools of enzyme activity has become apparent, few studies
      have estimated enzyme activity within discrete subcellular compartments. Here we
      present an approach to estimate near-membrane PDE activity. First, total PDE
      activity is measured using traditional PDE activity assays. Second, known cAMP
      concentrations are dialyzed into single cells and the spatial spread of cAMP is
      monitored using cyclic nucleotide-gated channels. Third, mathematical models are
      used to estimate the spatial distribution of PDE activity within cells. Using
      this three-tiered approach, we observed two pharmacologically distinct pools of
      PDE activity, a rolipram-sensitive pool and an 8-methoxymethyl IBMX (8MM-IBMX)
      sensitive pool. We observed that the rolipram-sensitive PDE (PDE4) was primarily
      responsible for cAMP hydrolysis near the plasma membrane. Finally, we observed
      that PDE4 was capable of blunting cAMP levels near the plasma membrane even when
      100 MUM cAMP were introduced into the cell via a patch pipette. Two compartment
      models predict that PDE activity near the plasma membrane, near cyclic nucleotide
      gated channels, was significantly lower than total cellular PDE activity and that
      a slow spatial spread of cAMP allowed PDE activity to effectively hydrolyze near
      membrane cAMP. These results imply that cAMP levels near the plasma membrane are
      distinct from those in other subcellular compartments; PDE activity is not
      uniform within cells; and localized pools of AC and PDE activities are
      responsible for controlling cAMP levels within distinct subcellular compartments.

PMID- 26201954
TI  - Surface activation of Pt nanoparticles synthesised by "hot injection" in the
      presence of oleylamine.
AB  - Oleylamine (OA) based "hot injection" colloidal synthesis offers a versatile
      approach to the synthesis of highly monodisperse metallic and multi-metallic
      alloyed nanostructures in the absence of potentially toxic and unstable phosphine
      compounds. For application in heterogeneous catalysis and electrocatalysis, the
      adsorbed OA species at the metal surfaces should be effectively removed without
      compromising the structure and composition of the nanostructures. Herein, we
      investigate the removal of OA from colloidal Pt nanoparticles through 1)
      "chemical methods" such as washing in acetic acid or ethanol, and ligand exchange
      with pyridine; and 2) thermal pre-treatment between 185 and 400  degrees C in
      air, H2 or Ar atmospheres. The electrochemical reactivity of Pt nanoparticles is
      acutely affected by the presence of surface organic impurities, making this
      material ideal for monitoring the effectiveness of OA removal. The results showed
      that thermal treatment in Ar at temperatures above 400  degrees C provides highly
      active particles, with reactivity comparable to the benchmark commercial
      catalyst, Pt/ETEK. The mechanism involved in thermal desorption of OA was also
      investigated by thermogravimetric analysis coupled to mass spectrometry (TGA-MS).
      Oxidation of HCOOH and adsorbed CO in acidic solution were used as test reactions
      to assess the Pt electrocatalytic activity. 

PMID- 26201955
TI  - Reply to Chiappetta et al.

PMID- 26201956
TI  - Influence of the distance between home and the hospital on patients with
      surgically resected non-small-cell lung cancer.
AB  - OBJECTIVES: There have been no previous reports examining how the travel distance
      affects the outcomes of non-small-cell lung cancer (NSCLC) patients. In this
      study, we examined the influence of the distance from home to the hospital on
      patients with NSCLC who underwent surgical resection. METHODS: From 2006 to 2011,
      607 consecutive patients with NSCLC who had undergone pulmonary resection were
      enrolled. The patients were divided into three groups according to the distance
      from their home to the hospital: 0 < 10, 10-30 and >30 km. We analysed the short
      term and long-term outcomes according to the group. RESULTS: Two hundred and
      ninety-six patients lived less than 10 km from the hospital, 111 patients lived
      10-30 km and 200 patients lived more than 30 km. There were no differences in the
      demographics, including age, European Cooperative Oncology Group performance
      status, histological type, surgical procedure and pathological stage, between the
      three groups. The mean postoperative hospital stay was as follows: 13.9 days in
      the <10 km group, 13.3 days in the 10-30 km group and 14.3 days in the >30 km
      group (P = 0.04). There were no significant differences in the median length of
      follow-up (50, 47, 43 months, P = 0.24), disease-free survival (DFS) (5-year DFS,
      68.1, 68.2 and 70.1%, P = 0.89) or overall survival (OS) (5-year OS, 80.6, 78.8
      and 79.4%, P = 0.99) between the three groups. CONCLUSIONS: The distance between
      home and the hospital was not found to influence the long-term outcomes of the
      patients with surgically resected NSCLC. Therefore, the travel distance should
      not represent a contraindication to surgical resection and postoperative therapy
      for NSCLC.

PMID- 26201957
TI  - Transfusion of 1 and 2 units of red blood cells does not increase mortality and
      organ failure in patients undergoing isolated coronary artery bypass grafting.
AB  - OBJECTIVES: In cardiac surgery, the association between red blood cell (RBC)
      transfusion and clinical outcome is elusive. We investigated in a large cohort of
      patients who underwent isolated coronary artery bypass grafting (CABG) the effect
      of transfusion of 1-2 units of leucocyte-depleted RBCs on mortality and
      multiorgan failure. METHODS: The investigation included all patients from July
      2009 to June 2014 who underwent CABG at our institution and received no (n =
      1478) or 1-2 units of RBCs (n = 1528). The primary end-point was 30-day
      mortality; secondary end-points were major organ dysfunction. A subgroup analysis
      assessed the effect of the duration of RBC storage on patient outcome.
      Statistical analysis was performed using propensity score (PS) adjustment.
      RESULTS: The 30-day mortality rate was 0.3% in the RBC- group and 0.2% in the
      RBC+ group. Compared with the RBC- group, PS-adjusted odds ratio (OR) of 30-day
      mortality in the RBC+ group was 0.29 [95% confidence interval (CI): 0.06-1.50; P
      = 0.14]. PS-adjusted OR of a 'prolonged intensive care unit (ICU) stay' (>48 h)
      was significantly higher in the RBC+ group than in the RBC- group [OR 1.49 (95%
      CI: 1.14-1.95); P = 0.004], but major clinical complications such as low cardiac
      output syndrome, stroke, haemofiltration, wound infection and prolonged
      mechanical ventilator support (>24 h) did not differ significantly between
      groups. Duration of blood storage was not independently associated with clinical
      outcome. CONCLUSIONS: Our data do not indicate a transfusion-related increase in
      mortality and multiorgan failure in patients undergoing isolated CABG.

PMID- 26201958
TI  - Postoperative oligo-recurrence of non-small-cell lung cancer: clinical features
      and survival?.
AB  - OBJECTIVES: Postoperative recurrences of non-small-cell lung cancer (NSCLC) are
      usually disseminated and systemic. Recently, the concept of oligo-recurrence,
      which is theoretically curable by definitive local therapy (DLT), has been
      proposed in several cancers. The aim of this study was to clarify clinical
      features and outcomes of patients with postoperative oligo-recurrence of NSCLC.
      METHODS: From 3275 patients with resected pathological stage IA-IIIB NSCLC
      between 1993 and 2011, a total of 768 patients who developed recurrence were
      included in this study. Oligo-recurrence was defined as 1-3 loco-regional or
      distant recurrent lesions restricted to a single organ. Other recurrences were
      classified as poly-recurrence. Second primary lung cancers and suspected lesions
      were excluded. DLT included surgery, stereotactic radiotherapy and radiotherapy
      with a 45 Gy or higher dose, performed with curative intent. RESULTS: Oligo
      recurrence was identified in 162 (21%) patients, mainly as a solitary recurrence
      (n = 129, 80%) in regional lymph nodes, brain, lung, bone and adrenal gland, and
      the proportion of patients with oligo-recurrence increased gradually year by
      year. The patients with oligo-recurrence had more early-staged disease at initial
      surgery and a longer time to recurrence than those with poly-recurrence. The
      entire population of oligo-recurrence patients had better post-recurrence
      survival (PRS) than those with poly-recurrence (5-year PRS: 32.9 vs 9.9%, P <
      0.001). For oligo-recurrence, DLT was totally conducted in 105 (65%) patients as
      initial treatment. Multivariate analyses revealed that the initial DLT was
      associated with improved PRS [odds ratio (OR) 0.44; 95% confidence interval (CI)
      0.29-0.68]. The recurrence location and initial pathological stage did not affect
      PRS. The 5-year PRS and postoperative progression-free survival rates after DLT
      were 38.6 and 22.3%, respectively. Of the 10 long-term (>=5-year) progression
      free survivors, 9 were those with a solitary recurrence. CONCLUSIONS: Initial DLT
      for oligo-recurrence achieved favourable PRS in a selected population. Oligo
      recurrence curable by DLT was found in a subset of patients who received DLT,
      mostly as a solitary recurrence.

PMID- 26201959
TI  - High incidence of vascular complication after computed tomography guided lung
      biopsy: what's the matter, the patient or the technique?

PMID- 26201961
TI  - Including or excluding toxicity test data for development of a geometric mean.

PMID- 26201960
TI  - Kinase inhibitor screening identifies CDK4 as a potential therapeutic target for
      melanoma.
AB  - Despite recent advances in targeted therapies and immunotherapies metastatic
      melanoma remains only rarely curable. The objective of the present study was to
      identify novel therapeutic targets for metastatic melanoma. A library of 160 well
      characterised and potent protein kinase inhibitors was screened in the BRAF
      mutant cell line Sk-Mel-28, and the NRAS mutant Sk-Mel-2, using proliferation
      assays. Of the 160 inhibitors tested, 20 achieved >50% growth inhibition in both
      cell lines. Six of the 20 were cyclin dependent kinase (CDK) inhibitors,
      including two CDK4 inhibitors. Fascaplysin, a synthetic CDK4 inhibitor, was
      further tested in 8 melanoma cell lines. The concentration of fascaplysin
      required to inhibit growth by 50% (IC50 value) ranged from 0.03 to 0.22 uM.
      Fascaplysin also inhibited clonogenic growth and induced apoptosis. Sensitivity
      to PD0332991, a therapeutic CDK4/6 inhibitor was also evaluated in the melanoma
      cell lines. PD0332991 IC50 values ranged from 0.13 to 2.29 uM. Similar to
      fascaplysin, PD0332991 inhibited clonogenic growth of melanoma cells and induced
      apoptosis. Higher levels of CDK4 protein correlated with lower sensitivity to
      PD0332991 in the cell lines. Combined treatment with PD0332991 and the BRAF
      inhibitor PLX4032, showed additive anti-proliferative effects in the BRAF mutant
      cell line Malme-3M. In summary, targeting CDK4 inhibits growth and induces
      apoptosis in melanoma cells in vitro, suggesting that CDK4 may be a rational
      therapeutic target for metastatic melanoma. 

PMID- 26201963
TI  - Early markers of right heart involvement in regular smokers by Pocket Size
      Imaging Device.
AB  - PURPOSE: To test the diagnostic power of Pocket Size Imaging Device (PSID) in
      detecting early signs of right heart (RH) involvement in regular smokers (RS)
      free of overt cardiac involvement. METHODS: One-hundred-forty-three regular
      smokers and 51 healthy controls, comparable for age and sex, underwent physical
      exam (PE), PSID exam and standard echocardiography. Based on a simplified Boston
      score, >=1 of clinical signs (jugular venous distension, hepatomegaly, peripheral
      pitting oedema and abnormal pulmonary sounds) were considered indicative of RH
      involvement. A composite score (1 to 4) obtained by summing the points of four
      quantitative RH abnormalities detectable by PSID (inferior vena cava [IVC]
      dilatation, reduced IVC respiratory variation, right ventricular dilatation and
      right atrial dilatation), was generated and >=1 of PSID abnormal signs was
      considered indicative of RH involvement. RESULTS: Boston score was not
      significantly different between the two groups. By using PSID, smokers exhibited
      greater IVC diameter (p < 0.0001), right atrial diameter (p < 0.002) and higher
      PSID score (p < 0.005) than controls. Compared to PE, the additional diagnostic
      power of PSID (>=1 abnormal sign of both Boston and PSID score) was 44.9% in
      smokers. By dividing smokers in tertiles according to number of cigarettes per
      day, the third tertile showed the largest values of both IVC and right atrial
      dimension. Differences were confirmed by standard echocardiography.
      Reproducibility of PSID measurements and concordance of linear measurements
      between PSID and standard echo measurements was very good except for concordance
      of right ventricular basal diameter. CONCLUSIONS: PSID detects early ultrasound
      signs of RH involvement in regular otherwise healthy smokers in comparison with
      PE.

PMID- 26201964
TI  - Does the Compliance to Intravesical BCG Differ between Common Clinical Practice
      and International Multicentric Trials?
AB  - INTRODUCTION: The aim of this study was to analyze the reasons for intravesical
      BCG interruption in clinical practice. BCG for at least one year is advocated as
      the best regimen to treat high-risk non-muscle invasive bladder cancer (NMIBC).
      However, almost 50% of patients don't complete it. Toxicity accounts for 10% of
      dropouts in international trials. MATERIALS AND METHODS: Patients with T1HG NMIBC
      undergoing 1-year BCG were enrolled in this study. BCG was administered for one
      year. Toxicity and causes of treatment interruption were recorded. RESULTS: A
      total of 411 patients were enrolled in the study. Out of these total number of
      patients, 380 (92.5%) completed the induction cycle and 215 (52.3%) completed one
      year. Toxicity requiring interruption or postponement was recorded in 25 (6.1%)
      and 60 (14.6%) patients. Ninety-three patients (30.2%) stopped BCG, 9 (9.7%) for
      recurrence and 14 (15.1%) for grade-3 toxicity. Intriguingly, 55 (59.1%) patients
      refused BCG due to mild discomfort and deterioration in quality of social life.
      CONCLUSIONS: Grades 2-3 toxicity causes BCG interruption in a few cases. Almost
      60% of interruptions are attributable to persistent grade-1 toxicity, which is
      inadequately treated.

PMID- 26201965
TI  - Whole-exome sequencing of a rare case of familial childhood acute lymphoblastic
      leukemia reveals putative predisposing mutations in Fanconi anemia genes.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric
      cancer. While the multi-step model of pediatric leukemogenesis suggests interplay
      between constitutional and somatic genomes, the role of inherited genetic
      variability remains largely undescribed. Nonsyndromic familial ALL, although
      extremely rare, provides the ideal setting to study inherited contributions to
      ALL. Toward this goal, we sequenced the exomes of a childhood ALL family
      consisting of mother, father and two non-twinned siblings diagnosed with
      concordant pre-B hyperdiploid ALL and previously shown to have inherited a rare
      form of PRDM9, a histone H3 methyltransferase involved in crossing-over at
      recombination hotspots and Holliday junctions. We postulated that inheritance of
      additional rare disadvantaging variants in predisposing cancer genes could affect
      genomic stability and lead to increased risk of hyperdiploid ALL within this
      family. METHODS: Whole exomes were captured using Agilent's SureSelect kit and
      sequenced on the Life Technologies SOLiD System. We applied a data reduction
      strategy to identify candidate variants shared by both affected siblings. Under a
      recessive disease model, we focused on rare non-synonymous or frame-shift
      variants in leukemia predisposing pathways. RESULTS: Though the family was
      nonsyndromic, we identified a combination of rare variants in Fanconi anemia (FA)
      genes FANCP/SLX4 (compound heterozygote - rs137976282/rs79842542) and FANCA
      (rs61753269) and a rare homozygous variant in the Holliday junction resolvase
      GEN1 (rs16981869). These variants, predicted to affect protein function, were
      previously identified in familial breast cancer cases. Based on our in-house
      database of 369 childhood ALL exomes, the sibs were the only patients to carry
      this particularly rare combination and only a single hyperdiploid patient was
      heterozygote at both FANCP/SLX4 positions, while no FANCA variant allele carriers
      were identified. FANCA is the most commonly mutated gene in FA and is essential
      for resolving DNA interstrand cross-links during replication. FANCP/SLX4 and GEN1
      are involved in the cleavage of Holliday junctions and their mutated forms, in
      combination with the rare allele of PRDM9, could alter Holliday junction
      resolution leading to nondisjunction of chromosomes and segregation defects.
      CONCLUSION: Taken together, these results suggest that concomitant inheritance of
      rare variants in FANCA, FANCP/SLX4 and GEN1 on the specific genetic background of
      this familial case, could lead to increased genomic instability, hematopoietic
      dysfunction, and higher risk of childhood leukemia.

PMID- 26201966
TI  - Metformin effects on biochemical recurrence and metabolic signaling in the
      prostate.
AB  - BACKGROUND: Metformin has received considerable attention as a potential anti
      cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated
      decreased tumor growth with metformin, however the precise mechanisms are
      unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR)
      in a large clinical database followed by evaluating metabolic signaling changes
      in a cohort of men undergoing prostate needle biopsy (PNB). METHODS: Men treated
      for localized PCa were identified in a comprehensive clinical database between
      2001 and 2010. Cox regression was performed to determine association with BCR
      relative to metformin use. We next identified a separate case-control cohort of
      men undergoing prostate needle biopsy (PNB) stratified by metformin use.
      Differences in mean IHC scores were compared with linear regression for
      phosphorylated IR, IGF-IR, AKT, and AMPK. RESULTS: One thousand seven hundred and
      thirty four men were evaluated for BCR with mean follow up of 41 months (range 1
      121 months). "Ever" metformin use was not associated with BCR (HR 1.12, 0.77
      1.65), however men reporting both pre/post-treatment metformin use had a 45%
      reduction in BCR (HR = 0.55 (0.31-0.96)). For the tissue-based study, 48
      metformin users and 42 controls underwent PNB. Significantly greater staining in
      phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin
      signaling proteins were seen in patients with PCa detected compared to those with
      negative PNB (P-values all <0.006). When stratified by metformin use, IGF-1R
      remained significantly elevated (P = 0.01) in men with PCa detected whereas p
      AMPK (P = 0.05) was elevated only in those without PCa. CONCLUSION: Metformin use
      is associated with reduced BCR after treatment of localized PCa when considering
      pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin
      signaling markers were significantly elevated compared to negative PNB patients.
      The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in
      negative PNBs suggests altered metabolic pathway activation precipitated by
      metformin use.

PMID- 26201967
TI  - De-agglomeration Effect of the US Pharmacopeia and Alberta Throats on Carrier
      Based Powders in Commercial Inhalation Products.
AB  - The US pharmacopeia (USP) and Alberta throats were recently reported to cause
      further de-agglomeration of carrier-free powders emitted from some dry powder
      inhalers (DPIs). This study assessed if they have similar influences on
      commercially available carrier-based DPIs. A straight tube, a USP throat, and an
      Alberta throat (non-coated and coated) were used for cascade impaction testing.
      Aerosol fine particle fraction (FPF <= 5 MUm) was computed to evaluate throat
      induced de-agglomeration. Computational fluid dynamics are employed to simulate
      airflow patterns and particle trajectories inside the USP and Alberta throats.
      For all tested products, no significant differences in the in vitro aerosol
      performance were observed between the USP throat and the straight tube. Using
      fine lactose carriers (<10 MUm), Symbicort((r)) and Oxis(TM) showed minimal
      impaction inside the Alberta throat and resulted in similar FPF among all
      induction ports. For products using coarse lactose carriers (>10 MUm), impaction
      frequency and energy inside the Alberta throat were significant. Further de
      agglomeration was noted inside the non-coated Alberta throat for Seretide((r))
      and Spiriva((r)), but agglomerates emitted from Relenza((r)), Ventolin((r)), and
      Foradil((r)) did not further break up into smaller fractions. The coated Alberta
      throat considerably reduced the FPF values of these products due to the high
      throat retention, but they generally agreed better with the in vivo data. In
      conclusion, depending on the powder formulation (including carrier particle
      size), the inhaler, and the induction port, further de-agglomeration could happen
      ex-inhaler and create differences in the in vitro measurements. 

PMID- 26201968
TI  - Relationship between cardiovascular risk and lipid testing in one health care
      system: a retrospective cohort study.
AB  - BACKGROUND: The US Preventive Services Taskforce (USPSTF) recommends routine
      lipid screening beginning age 35 for men [1]. For women age 20 and older, as well
      as men age 20-34, screening is recommended if cardiovascular risk factors are
      present. Prior research has focused on underutilization but not overuse of lipid
      testing. The objective is to document over- and under-use of lipid testing in an
      insured population of persons at low, moderate and high cardiovascular disease
      (CVD) risk for persons not already on statins. METHODS: The study is a
      retrospective cohort study that included all adults without prior CVD who were
      continuously enrolled in a large integrated healthcare system from 2005 to 2010.
      Measures included lipid test frequency extracted from administrative data and
      Framingham cardiovascular risk equations applied using electronic medical record
      data. Five year lipid testing patterns were examined by age, sex and CVD risk.
      Generalized linear models were used to estimate the relative risk for over
      testing associated with patient characteristics. RESULTS: Among males and females
      for whom testing is not recommended, 35.8 % and 61.5 % received at least one
      lipid test in the prior 5 years and 8.4 % and 24.4 % had two or more. Over
      testing was associated with age, race, comorbidity, primary care use and
      neighborhood income. Among individuals at moderate and high-risk (not already
      treated with statins) and for whom screening is recommended, between 21.4 % and
      25.1 % of individuals received no screening in the prior 5 years. CONCLUSIONS:
      Based on USPSTF lipid screening recommendations, this study documents substantial
      over-testing among individuals with low CVD risk and under-testing among
      individuals with moderate to high-risk not already on statins. Opportunity exists
      to better focus lipid screening efforts appropriate to CVD risk.

PMID- 26201969
TI  - Effect of surface treatments on the surface morphology, corrosion property, and
      antibacterial property of Ti-10Cu sintered alloy.
AB  - Ti-10Cu sintered alloy has shown strong antibacterial properties against S.
      aureus and E. coli and good cell biocompatibility in vitro and in vivo,
      displaying potential application as an implant material. Surface treatments are
      always applied to implants to improve the surface biocompatibility. In this
      paper, several typically used surface treatments, including sandblasting (SB),
      sandblasted and large-grits acid etching (SLA), and alkaline heat treatment (AH)
      were chosen to modify the Ti-10Cu. A cp-Ti (commercially pure titanium) sample
      was used as control sample. The effect of surface treatments on the corrosion
      properties and antibacterial properties of the Ti-10Cu sintered alloy was
      investigated. After SB and SLA treatments, a rough surface with a TiO2 layer was
      formed on the surface, which reduced the corrosion resistance and enhanced the Ti
      and Cu ion release. After AH treatment, a smooth but microporous surface with a
      TiO2/titanate layer was formed, which improved slightly the corrosion resistance.
      However, the Cu ion and Ti ion release from the Ti-10Cu sample was promoted by AH
      treatment due to the fact that more Ti2Cu phases were exposed on the AH-treated
      Ti-10Cu sample. It was demonstrated that the Ti-10Cu samples after surface
      treatments still exhibited good antibacterial properties against S. aureus, which
      indicated that the surface treatment did not reduce the antibacterial activity.
      The control mechanism was thought to be related to the high Cu ion release even
      after surface treatments. It was expected that the surface treatments provided Ti
      10Cu sintered alloy with good surface bioactivity without reduction in
      antibacterial activity. 

PMID- 26201970
TI  - Identification of allergens in the box jellyfish Chironex yamaguchii that cause
      sting dermatitis.
AB  - BACKGROUND: Jellyfish stings cause painful, papular-urticarial eruptions due to
      the immediate allergic, acute toxic and persistent inflammatory responses. In
      spite of many marine accidents and their economic impact, modes of first-aid
      treatment remain conventional and specific allergen and medical treatment are not
      yet available. The purpose of this study was to define the specific allergen of
      the box jellyfish Chironex yamaguchii and to study the precise mechanism of the
      resulting dermatitis. METHODS: We comprehensively studied the immunoglobulin
      binding molecules from the box jellyfish C. yamaguchii with a purification
      procedure and Western blotting, using sera from 1 patient and from several
      controls. RESULTS: From the nematocyst wall and spine, we detected IgG-binding
      acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion
      exchange chromatography. In addition, the 66-kDa protein was found to be an
      asparagine residue-coupled N-linked glycoprotein and the epitope resided in the
      protein fraction. We found that CqTX-A, the major toxic protein of the
      nematocyst, is also a heat-stable IgE-binding allergen. This was confirmed as a
      45-kDa protein by Western blot from both nematocyst extracts and purified CqTX-A.
      CONCLUSIONS: The detection of these proteins may, in part, explain the combined
      immediate allergic-toxic and persistent allergic responses. Hopefully, our
      findings will lead to the development of specific venom immunotherapy for marine
      professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis.

PMID- 26201971
TI  - Suitability of feeding and chewing time for estimation of feed intake in dairy
      cows.
AB  - Monitoring of feeding and rumination behaviour can provide useful information for
      dairy herd management. The feeding behaviour of dairy cows can be recorded by
      different techniques, such as video cameras, weighing troughs or chewing sensors.
      Among feeding characteristics, individual feed intake of cows is of utmost
      interest, but as weighing troughs have high space and cost requirements they are
      used primarily in research studies. The objective of the present study was to
      evaluate whether records on feeding time or chewing activity or a combination of
      both contain enough information to estimate feed intake with sufficient accuracy.
      Feed intake and feeding time per cow were recorded by means of weighing troughs.
      Concurrently, chewing activity of seven cows was recorded by MSR-ART pressure
      sensors during five to eight measuring days per cow. Feeding and chewing
      behaviour were evaluated in time slots (1 min) and additionally assigned to
      feeding bouts for further analysis. The 1 min time slots were classified into
      feeding/no feeding or chewing/no chewing by the two systems, and agreement was
      found in 92.2% of the records. On average, cows spent 270+/-39 min/day at the
      feeding troughs and chewed 262+/-48 min/day. The average fresh matter intake
      (FMI) was 49.6+/-5.1 kg/day. Feed intake was divided into 9.7 bouts/day during
      which cows fed in average 27.8+/-21.7 min/bout and chewed 27.0+/-23.1 min/bout.
      The correlation between FMI and feeding time was r=0.891 and between FMI and
      chewing time r=0.780 overall cows. Hence, both systems delivered suitable
      information for estimating feed intake. 

PMID- 26201972
TI  - Misleading FLAIR imaging pattern after glioma surgery with intraoperative MRI.
AB  - Intraoperative MRI (iMRI) allows a more detailed appreciation of the extent of
      resection than does conventional neurosurgery and results in longer overall
      survival in patients with malignant glioma. However, it is unknown whether the
      intraoperative application of contrast agent influences the early postsurgical
      MRI. The preceding iMRI could alter the signals of MR sequences in the early
      postsurgical MRI, especially in sequences influenced by T1 contrast. Hereby, we
      investigate such iMRI-induced influences on the fluid-attenuated inversion
      recovery (FLAIR) sequence. We retrospectively analyzed postsurgical T2w, T1w, and
      FLAIR images by visual inspection and by signal measurements in 46 patients with
      malignant gliomas after tumor resection. Of these, n = 25 patients were operated
      with conventional microsurgery, and n = 21 patients were operated with contrast
      enhanced iMRI-guided microsurgery. We measured signal intensity in the resection
      cavity, in the cerebrospinal fluid (CSF) of the ventricles, and in the normal
      brain tissue contralateral to the tumor-bearing hemisphere on axial FLAIR images
      and T1-weighted and T2-weighted images. In 18 patients, the FLAIR sequence
      revealed hyperintense signal changes of the CSF in the subarachnoid or
      ventricular spaces. Seventeen of these 18 patients had received intraoperative
      MRI. In both FLAIR and T1-weighted images, the signal of the CSF in the
      ventricles was significantly higher in patients with iMRI than in patients
      without iMRI. The intraoperative application of contrast agent that is used for
      iMRI significantly influences postsurgical MRI within the first 72 h. We found
      hyperintense signal changes of the CSF in the FLAIR sequence in the subarachnoid
      and intraventricular spaces mimicking subarachnoid hemorrhage. The findings may
      result in a misdiagnosis of subarachnoid hemorrhage (SAH) in these patients.

PMID- 26201973
TI  - Observational methods to assess the effectiveness of screening colonoscopy in
      reducing right colon cancer mortality risk: SCOLAR.
AB  - AIMS: Screening colonoscopy's effectiveness in reducing risk of death from right
      colon cancers remains unclear. Methodological challenges of existing
      observational studies addressing this issue motivated the design of
      'Effectiveness of Screening for Colorectal Cancer in Average-Risk Adults
      (SCOLAR)'. METHODS: SCOLAR is a nested case-control study based on two large
      integrated health systems. This affords access to a large, well-defined
      historical cohort linked to integrated data on cancer outcomes, patient
      eligibility, test indications and important confounders. RESULTS: We found
      electronic data adequate for excluding ineligible patients (except family
      history), but not the detailed information needed for test indication assignment.
      CONCLUSION: The lessons of SCOLAR's design and implementation may be useful for
      future studies seeking to evaluate the effectiveness of screening tests in
      community settings.

PMID- 26201974
TI  - Retinoic acid induces macrophage cholesterol efflux and inhibits atherosclerotic
      plaque formation in apoE-deficient mice.
AB  - It has been suggested that retinoic acid (RA) has a potential role in the
      prevention of atherosclerotic CVD. In the present study, we used J774A.1 cell
      lines and primary peritoneal macrophages to investigate the protective effects of
      RA on foam cell formation and atherogenesis in apoE-deficient (apoE- / -) mice. A
      total of twenty male apoE- / - mice (n 10 animals per group), aged 8 weeks, were
      fed on a high-fat diet (HFD) and treated with vehicle or 9-cis-RA for 8 weeks.
      The atherosclerotic plaque area in the aortic sinus of mice in the 9-cis-RA group
      was 40.7 % less than that of mice in the control group (P< 0.01). Mouse
      peritoneal macrophages from the 9-cis-RA group had higher protein expression
      levels of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) than those
      from the control group. Serum total and LDL-cholesterol concentrations were lower
      in the 9-cis-RA group than in the control group (P< 0.05). In vitro studies
      showed that incubation of cholesterol-loaded J774A.1 macrophages with 9-cis-RA
      (0.1, 1 and 10 MUmol/l) induced cholesterol efflux in a dose-dependent manner.
      The 9-cis-RA treatment markedly attenuated lipid accumulation in macrophages
      exposed to oxidised LDL. Moreover, treatment with 9-cis-RA significantly
      increased the protein expression levels of ABCA1 and ABCG1 in J774A.1 macrophages
      in a dose-dependent manner. Furthermore, 9-cis-RA dose-dependently enhanced the
      protein expression level of liver X receptor-alpha (LXRalpha), the upstream
      regulator of ABCA1 and ABCG1. Taken together, the present results show that 9-cis
      RA suppresses foam cell formation and prevents HFD-induced atherogenesis via the
      LXRalpha-dependent up-regulation of ABCA1 and ABCG1.

PMID- 26201975
TI  - Interleukin-10 receptor-1 expression in monocyte-derived antigen-presenting cell
      populations: dendritic cells partially escape from IL-10's inhibitory mechanisms.

PMID- 26201976
TI  - Giant cell myositis responsive to combined corticosteroids and immunoglobulin.
AB  - A 70-year-old man presented with respiratory distress and proximal muscle
      weakness shortly after biopsy of a left forearm mass. The biopsy showed giant
      cell myositis, and serological investigations identified a grossly elevated serum
      creatine kinase level, suggesting skeletal muscle damage. Serum troponin T was
      also high, but troponin I was normal. Serum antiacetylcholine receptor antibodies
      were positive, and imaging showed a thymoma. He recovered well following
      intravenous immunoglobulin and corticosteroids, and later underwent thymectomy.
      He is currently in sustained remission, with no clinically detectable myasthenia,
      but subsequently, developed hypogammaglobulinaemia. Neurologists should remember
      giant cell myositis/myocarditis can occur in patients who have myasthenia gravis
      with thymoma, as it is potentially fatal, but may respond to immunosuppression. 

PMID- 26201977
TI  - Mitochondrial disease: mimics and chameleons.
AB  - Mitochondrial diseases are inherited disorders of oxidative phosphorylation that
      present with a multitude of clinical features in different combinations and with
      various inheritance patterns. To complicate the issue further, the clinical
      features of mitochondrial disorders overlap with common neurological and non
      neurological diseases. This presents a diagnostic challenge: when is a rare
      mitochondrial disease responsible for a more 'common or garden' neurological
      presentation, and how often are neurologists missing them in routine clinical
      practice? Here, we briefly review some common clinical features associated with
      mitochondrial disease, and provide some clues as to how patients with these
      mitochondrial disorders might be identified. We discuss both 'chameleons'
      mitochondrial disorders that may look like something else, and 'mimics'-other
      conditions that may clinically resemble mitochondrial disease. The diagnosis
      sometimes needs highly specialised tests, but the advent of 'next generation'
      sequencing will simplify the clinical approach over the next few years. 

PMID- 26201978
TI  - The challenge of diabetes in sub-Saharan Africa.

PMID- 26201979
TI  - Combination of dynamic magnetophoretic separation and stationary magnetic trap
      for highly sensitive and selective detection of Salmonella typhimurium in complex
      matrix.
AB  - Foodborne illnesses have always been a serious problem that threats public
      health, so it is necessary to develop a method that can detect the pathogens
      rapidly and sensitively. In this study, we designed a magnetic controlled
      microfluidic device which integrated the dynamic magnetophoretic separation and
      stationary magnetic trap together for sensitive and selective detection of
      Salmonella typhimurium (S. typhimurium). Coupled with immunomagnetic nanospheres
      (IMNs), this device could separate and enrich the target pathogens and realize
      the sensitive detection of target pathogens on chip. Based on the principle of
      sandwich immunoassays, the trapped target pathogens identified by streptavidin
      modified QDs (SA-QDs) were detected under an inverted fluorescence microscopy. A
      linear range was exhibited at the concentration from 1.0*10(4) to 1.0*10(6)
      colony-forming units/mL (CFU/mL), the limit of detection (LOD) was as low as
      5.4*10(3) CFU/mL in milk (considering the sample volume, the absolute detection
      limit corresponded to 540C FU). Compared with the device with stationary magnetic
      trap alone, the integrated device enhanced anti-interference ability and
      increased detection sensitivity through dynamic magnetophoretic separation, and
      made the detection in complex samples more accurate. In addition, it had
      excellent specificity and good reproducibility. The developed system provides a
      rapid, sensitive and accurate approach to detect pathogens in practice samples.

PMID- 26201980
TI  - Development of L-lactate dehydrogenase biosensor based on porous silicon resonant
      microcavities as fluorescence enhancers.
AB  - The up-regulation of L-lactate dehydrogenase (LDH), an intracellular enzyme
      present in most of all body tissues, is indicative of several pathological
      conditions and cellular death. Herein, we demonstrate LDH detection using porous
      silicon (pSi) microcavities as a luminescence-enhancing optical biosensing
      platform. Non-fluorescent resazurin was covalently attached onto the pSi surface
      via thermal hydrocarbonisation, thermal hydrosylilation and acylation. Each
      surface modification step was confirmed by means of FTIR and the optical shifts
      of the resonance wavelength of the microcavity. Thermal hydrocarbonisation also
      afforded excellent surface stability, ensuring that the resazurin was not reduced
      on the pSi surface. Using a pSi microcavity biosensor, the fluorescence signal
      upon detection of LDH was amplified by 10 and 5-fold compared to that of a single
      layer and a detuned microcavity, respectively, giving a limit of detection of
      0.08 U/ml. The biosensor showed a linear response between 0.16 and 6.5 U/ml,
      covering the concentration range of LDH in normal as well as damaged tissues. The
      biosensor was selective for LDH and did not produce a signal upon incubation with
      another NAD-dependant enzyme L-glutamic dehydrogenase. The use of the pSi
      microcavity as a sensing platform reduced reagent usage by 30% and analysis time
      threefold compared to the standard LDH assay in solution.

PMID- 26201981
TI  - Tyrosinase conjugated reduced graphene oxide based biointerface for bisphenol A
      sensor.
AB  - We have fabricated a nanocomposite of reduced graphene oxide (rGO) sheets and
      chitosan (Cn) polymer based highly sensitive electrochemical biosensor for
      detection of bisphenol A (BPA). The two-dimensional structure and chemical
      functionality of rGO and Cn provide an excellent electrode surface for loading of
      tyrosinase enzyme molecules. This rGO-Cn nanocomposite is capable of effectively
      utilizing their superior conductivity, larger effective surface area and superior
      electrochemical performance due to its synergistic effect between rGO and Cn. The
      structural, morphological and electrochemical characterizations of nanocomposite
      sheets have been performed by electron microscopy, X-ray diffraction, FTIR and
      Potentiostat/Galvanostat techniques. This fabricated biosensor is sensitive to
      nanomolar (0.74 nM) concentration of BPA and detection time is 10s compared to
      conventional BPA ELISA kit (0.3 ug/L and 2.5h). The rGO-Cn based biosensor
      exhibits a higher sensitivity (83.3 uA nM(-1) cm(-2)), wider linearity (0.01-50
      uM) with good selectivity towards BPA. This biosensor is capable to quantify real
      sample of BPA using packaged drinking water bottles. This rGO-Cn nanocomposite
      sheets emerges as a potential electrode material for detection of other
      estrogenic substrate.

PMID- 26201982
TI  - Simultaneous electrochemical magneto genosensing of foodborne bacteria based on
      triple-tagging multiplex amplification.
AB  - Simultaneous detection of Salmonella enterica, Listeria monocytogenes and
      Escherichia coli based on triple-tagging multiplex PCR and electrochemical
      magneto genosensing on silica magnetic particles is reported. A set of tagging
      primers were selected for the specific amplification of yfiR (375 bp), hlyA (234
      bp) and eaeA (151bp), being one of the primers for each set labelled with
      fluorescein, biotin and digoxigenin coding for S. enterica, L. monocytogenes and
      E. coli, respectively. Afterwards, electrochemical magneto genosensing of the
      bacteria was achieved by using silica magnetic particles as a carrier and three
      different electrochemical reporters, specific for each pathogen. This method was
      able to clearly distinguish among the pathogenic bacteria tested within 50 min,
      with detection limits ranging from 12 to 46 pg MUL(-1).

PMID- 26201983
TI  - In situ deposition of Prussian blue on mesoporous carbon nanosphere for sensitive
      electrochemical immunoassay.
AB  - A Prussian blue (PB) functionalized mesoporous carbon nanosphere (MCN) composite
      was prepared for loading signal antibody and high-content glucose oxidase (GOD)
      to obtain a new nanoprobe for sensitive electrochemical immunoassay. The MCN
      nanocarrier with an average diameter of 180 nm was synthesized by using
      mesoporous silica nanosphere as a hard template in combination with a
      hydrothermal carbonization method. This hydrophilic carbon nanomaterial provided
      an ideal platform for in situ deposition of high-content PB to form the MCN-PB
      nanocomposite. Based on the step-wise assembly of polyelectrolyte and gold
      nanoparticles (Au NPs) on the negative-charged nanocomposite, signal antibody and
      high-content GOD were loaded on this nanocarrier to obtain the nanoprobe. After a
      sandwich immunoreaction at an Au NPs-modified screen-printed carbon electrode
      based immunosensor, the nanoprobes were quantitatively captured on the electrode
      surface to produce sensitive electrochemical response with a PB-mediated GOD
      catalytic reaction for immunoassay. The high loading of PB and GOD on the
      nanoprobe greatly amplified the electrochemical signal, leading to the
      development of a new immunoassay method with high sensitivity. Using human
      immunoglobulin G as a model analyte, excellent analytical performance including a
      wide linear range from 0.01 to 100 ng/mL and a low detection limit down to 7.8
      pg/mL was obtained. Additionally, the immunosensor showed high specificity,
      satisfactory stability and repeatability as well as acceptable reliability. The
      PB-mediated GOD electrochemical system well excluded the conventional
      interference from the dissolved oxygen. Thus this immunoassay method provides
      great potentials for practical applications.

PMID- 26201984
TI  - Electrochemical assay of alpha-glucosidase activity and the inhibitor screening
      in cell medium.
AB  - An electrochemical method is established in this work for the assay of alpha
      glucosidase activity and the inhibitor screening through one-step displacement
      reaction, which can be directly used in cell medium. The displacement reaction
      can be achieved via strong binding of 4-aminophenyl-alpha-D-glucopyranoside
      (pAPG)/magnetic nanoparticles (MNPs) to pyrene boric acid (PBA) immobilized on
      the surface of graphite electrode (GE), compared to that of dopamine (DA)/sliver
      nanoparticles (AgNPs). Since alpha-glucosidase can specifically catalyze
      MNPs/pAPG into MNPs/pAP which has no binding capacity with PBA, the activity of
      both isolated and membrane bound enzyme can be well evaluated by using this
      proposed method. Meanwhile, signal amplification can be accomplished via the
      immobilization of DA at the outer layer of AgNPs, and the accuracy can be
      strengthened through magnetic separation. Moreover, this method can also be
      utilized for inhibitor screening not only in the medium containing the enzyme but
      also in cell medium. With good precision and accuracy, it may be extended to
      other proteases and their inhibitors as well.

PMID- 26201985
TI  - Ultrasensitive electrochemical immunosensor based on dual signal amplification
      process for p16(INK4a) cervical cancer detection in clinical samples.
AB  - The p16(INK4a) (p16) is a cyclin-dependent kinase inhibitor, which has been
      evaluated in several studies as a diagnostic marker of cervical cancer.
      Immunostaining using p16 specific antibody has confirmed an over-expression of
      p16 protein in cervical cancer cells and its association with disease
      progression. This article reports an ultrasensitive electrochemical immunosensor
      for specific detection of p16 and demonstrates its performance for detection of
      solubilized p16 protein in cell lysates obtained from patients. Sandwich-based
      immunoreaction couple with double signal amplification strategy based on
      catalytic enlargement of particle tag was used for high sensitivity and
      specificity. The conditions were optimized to create an immunoassay protocol.
      Disposable screen-printed electrode modified with capture antibodies (Ab1) was
      selected for further implementation towards point-of-care diagnostics. Small gold
      nanoparticles (15 nm diameter) conjugated with detection antibodies (Ab2) were
      found to better serve as a detection label due to limited interference with
      antigen-antibody interaction. Double signal enhancement was performed by
      sequential depositions of gold and silver layers. This gave the sensitivity of
      1.78 MUA mL(ng GST-p16)(-1) cm(-2) and detection limit of 1.3 ng mL(-1) for GST
      p16 protein which is equivalent to 0.49 ng mL(-1) for p16 protein and 28 cells
      for HeLa cervical cancer cells. In addition to purified protein, the proposed
      immunosensor effectively detected elevated p16 level in cervical swab samples
      obtained from 10 patients with positive result from standard Pap smear test,
      indicating that an electrochemical immunosensors hold an excellent promise for
      detection of cervical cancer in clinical setting.

PMID- 26201986
TI  - Impact of diabetes on healthcare costs in a population-based cohort: a cost
      analysis.
AB  - AIMS: To estimate the healthcare costs attributable to diabetes in Ontario,
      Canada using a propensity-matched control design and health administrative data
      from the perspective of a single-payer healthcare system. METHODS: Incident
      diabetes cases among adults in Ontario were identified from the Ontario Diabetes
      Database between 2004 and 2012 and matched 1:3 to control subjects without
      diabetes identified in health administrative databases on the basis of
      sociodemographics and propensity score. Using a comprehensive source of
      administrative databases, direct per-person costs (Canadian dollars 2012) were
      calculated. A cost analysis was performed to calculate the attributable costs of
      diabetes; i.e. the difference of costs between patients with diabetes and control
      subjects without diabetes. RESULTS: The study sample included 699 042 incident
      diabetes cases. The costs attributable to diabetes were greatest in the year
      after diagnosis [C$3,785 (95% CI 3708, 3862) per person for women and C$3,826
      (95% CI 3751, 3901) for men], increasing substantially for older age groups and
      patients who died during follow-up. After accounting for baseline comorbidities,
      attributable costs were primarily incurred through inpatient acute
      hospitalizations, physician visits and prescription medications and assistive
      devices. CONCLUSIONS: The excess healthcare costs attributable to diabetes are
      substantial and pose a significant clinical and public health challenge. This
      burden is an important consideration for decision-makers, particularly given
      increasing concern over the sustainability of the healthcare system, aging
      population structure and increasing prevalence of diabetic risk factors, such as
      obesity.

PMID- 26201988
TI  - Amantadine inhibits cellular proliferation and induces the apoptosis of
      hepatocellular cancer cells in vitro.
AB  - Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies
      worldwide, and its incidence associated with viral infection has increased in
      recent years. Amantadine is a tricyclic symmetric amine that can effectively
      protect against the hepatitis C virus. However, its antitumor properties remain
      unclear. In the present study, the effects of amantadine on tumor cell viability,
      cell cycle regulation and apoptosis were investigated. The growth of HepG2 and
      SMMC-7721 cells (HCC cell lines) was detected by an MTT assay. Flow cytometry was
      used to investigate cell cycle regulation and apoptosis. Reverse transcription
      quantitative polymerase chain reaction and western blot analysis were also
      performed to examine the expression of cell cycle- and apoptosis-related genes
      and proteins, including cyclin E, cyclin D1, cyclin-dependent kinase 2 (CDK2), B
      cell lymphoma 2 (Bcl-2) and Bax. Our results demonstrated that amantadine
      markedly inhibited the proliferation of HepG2 and SMMC-7721 cells in a dose- and
      time-dependent manner and arrested the cell cycle at the G0/G1 phase. The levels
      of the cell cycle-related genes and proteins (cyclin D1, cyclin E and CDK2) were
      reduced by amantadine, and apoptosis was significantly induced. Amantadine
      treatment also reduced Bcl-2 and increased the Bax protein and mRNA levels.
      Additionally, Bcl-2/Bax ratios were lower in the two HCC cell lines following
      amantadine treatment. Collectively, these results emphasize the role of
      amantadine in suppressing proliferation and inducing apoptosis in HCC cells,
      advocating its use as a novel tumor-suppressive therapeutic candidate.

PMID- 26201987
TI  - Generic lamotrigine versus brand-name Lamictal bioequivalence in patients with
      epilepsy: A field test of the FDA bioequivalence standard.
AB  - OBJECTIVE: To test the current U.S. Food and Drug Administration (FDA)
      bioequivalence standard in a comparison of generic and brand-name drug
      pharmacokinetic (PK) performance in "generic-brittle" patients with epilepsy
      under clinical use conditions. METHODS: This randomized, double-blind, multiple
      dose, steady-state, fully replicated bioequivalence study compared generic
      lamotrigine to brand-name Lamictal in "generic-brittle" patients with epilepsy (n
      = 34) who were already taking lamotrigine. Patients were repeatedly switched
      between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at
      the end of each 2-week treatment period yielded two 12-h PK profiles for brand
      name and generic forms for each patient. Steady-state area under the curve (AUC),
      peak plasma concentration (Cmax ), and minimum plasma concentration (Cmin ) data
      were subjected to conventional average bioequivalence (ABE) analysis, reference
      scaled ABE analysis, and within-subject variability (WSV) comparisons. In
      addition, generic-versus-brand comparisons in individual patients were performed.
      Secondary clinical outcomes included seizure frequency and adverse events.
      RESULTS: Generic demonstrated bioequivalence to brand. The 90% confidence
      intervals of the mean for steady-state AUC, Cmax , and Cmin for generic-versus
      brand were 97.2-101.6%, 98.8-104.5%, and 93.4-101.0%, respectively. The WSV of
      generic and brand were also similar. Individual patient PK ratios for generic
      versus-brand were similar but not identical, in part because brand-versus-brand
      profiles were not identical, even though subjects were rechallenged with the same
      product. Few subjects had seizure exacerbations or tolerability issues with
      product switching. One subject, however, reported 267 focal motor seizures,
      primarily on generic, although his brand and generic PK profiles were practically
      identical. SIGNIFICANCE: Some neurologists question whether bioequivalence in
      healthy volunteers ensures therapeutic equivalence of brand and generic
      antiepileptic drugs in patients with epilepsy, who may be at increased risk for
      problems with brand-to-generic switching. Bioequivalence results in "generic
      brittle" patients with epilepsy under clinical conditions support the soundness
      of the FDA bioequivalence standards. Adverse events on generic were not related
      to the small, allowable PK differences between generic and brand.

PMID- 26201989
TI  - Ester-Mediated Amide Bond Formation Driven by Wet-Dry Cycles: A Possible Path to
      Polypeptides on the Prebiotic Earth.
AB  - Although it is generally accepted that amino acids were present on the prebiotic
      Earth, the mechanism by which alpha-amino acids were condensed into polypeptides
      before the emergence of enzymes remains unsolved. Here, we demonstrate a
      prebiotically plausible mechanism for peptide (amide) bond formation that is
      enabled by alpha-hydroxy acids, which were likely present along with amino acids
      on the early Earth. Together, alpha-hydroxy acids and alpha-amino acids form
      depsipeptides-oligomers with a combination of ester and amide linkages-in model
      prebiotic reactions that are driven by wet-cool/dry-hot cycles. Through a
      combination of ester-amide bond exchange and ester bond hydrolysis, depsipeptides
      are enriched with amino acids over time. These results support a long-standing
      hypothesis that peptides might have arisen from ester-based precursors. 

PMID- 26201990
TI  - Community-based amblyopia screening program for early detection in Iran: a
      repeated cross-sectional study from 1996 to 2013.

PMID- 26201991
TI  - Myo5b knockout mice as a model of microvillus inclusion disease.
AB  - Inherited MYO5B mutations have recently been associated with microvillus
      inclusion disease (MVID), an autosomal recessive syndrome characterized by
      intractable, life-threatening, watery diarrhea appearing shortly after birth.
      Characterization of the molecular mechanisms underlying this disease and
      development of novel therapeutic approaches is hampered by the lack of animal
      models. In this study we describe the phenotype of a novel mouse model with
      targeted inactivation of Myo5b. Myo5b knockout mice show perinatal mortality,
      diarrhea and the characteristic mislocalization of apical and basolateral plasma
      membrane markers in enterocytes. Moreover, in transmission electron preparations,
      we observed microvillus atrophy and the presence of microvillus inclusion bodies.
      Importantly, Myo5b knockout embryos at day 20 of gestation already display all
      these structural defects, indicating that they are tissue autonomous rather than
      secondary to environmental cues, such as the long-term absence of nutrients in
      the intestine. Myo5b knockout mice closely resemble the phenotype of MVID
      patients and constitute a useful model to further investigate the underlying
      molecular mechanism of this disease and to preclinically assess the efficacy of
      novel therapeutic approaches. 

PMID- 26201992
TI  - "You know your own fistula, it becomes a part of you"--Patient perspectives on
      vascular access: A semistructured interview study.
AB  - The success of hemodialysis depends on functional vascular access but such an
      invasive, semipermanent intervention can be confronting for patients. Vascular
      access complications are potentially life threatening and reduce treatment
      satisfaction and quality of life. This study aims to describe patient
      perspectives on vascular access. Face-to-face, semistructured interviews were
      conducted with 26 adult patients receiving hemodialysis with any form of vascular
      access at two dialysis units in Australia. The transcripts were analyzed using
      thematic analysis. We identified five major themes describing patient
      perspectives on vascular access: developing mental fortitude for access
      (accepting necessity for survival, self-advocacy, experiential confidence and
      competency, dependency on others, gaining vascular knowledge), device
      intrusiveness on the body (restricting normal function, finding compensatory
      solutions, bodily invasion, confronting appearance), inhibiting pain (aversion to
      surgery, persisting needle anxieties), exposure to dire health consequences
      (resigning to inevitable failure, anticipating serious complications,
      technological skepticism, wary of medical incompetence), and imposing burdens
      (generating additional expenses, encumbering family members). Patients with a
      vascular access rely on a precarious lifeline, which is confronting, intrusive,
      and burdensome. Some develop mental resilience to cope with the pain and
      invasiveness of vascular access. The results suggest that more attention to
      address needle anxieties, self-advocacy, lifestyle disruption, fear of
      complications, and concern for caregiver burden may improve treatment
      satisfaction and outcomes for patients on hemodialysis. 

PMID- 26201993
TI  - Furostanolic saponins from Trigonella foenum-graecum alleviate diet-induced
      glucose intolerance and hepatic fat accumulation.
AB  - SCOPE: The objective of this study was to evaluate the effect of fenugreek
      furostanolic saponins (Fenfuro(TM) ) either alone or in combination with
      chlorogenic acid (GCB-70(TM) ) on insulin resistance in mice. METHODS AND
      RESULTS: Male C57BL/6J mice were subjected to a normal or high-fat diet (HFD) and
      were randomly assigned to receive Fenfuro(TM) , GCB-70(TM) , or their combination
      for 24 wk. Metabolic parameters, glucose tolerance, serum triglycerides, cardiac
      function, and hepatic insulin signaling were evaluated using indirect open
      circuit calorimetry, intraperitoneal glucose tolerance test, oil red O staining,
      echocardiography, and Western blotting, respectively. Intraperitoneal glucose
      tolerance test revealed glucose intolerance in the mice receiving HFD, which was
      attenuated by Fenfuro(TM) . Serum triglyceride that was elevated following an HFD
      was reconciled by both Fenfuro(TM) and the combination. HFD compromised
      myocardial contractile function, which was unaffected by the treatment. Insulin
      stimulated phosphorylation of Protein kinase B (AKT) in the liver was attenuated
      in mice receiving HFD, which was partially rescued by GCB-70(TM) . Neither
      treatment altered metabolic parameters or energy expenditure. CONCLUSION:
      Collectively, our data suggest that fenugreek furostanolic saponins and green
      coffee bean extract may have potential benefits in treating insulin resistance
      and related conditions.

PMID- 26201995
TI  - Are there geographic mosaics of mycorrhizal specificity and partial
      mycoheterotrophy? A case study in Moneses uniflora (Ericaceae).

PMID- 26201994
TI  - Distal pancreatectomy with celiac axis resection: what are the added risks?
AB  - BACKGROUND: Reported series of a distal pancreatectomy with celiac axis resection
      (DP-CAR) are either small or not adequately controlled. The aim of this analysis
      was to report a multicentre series of modified Appleby procedures with a
      comparison group to determine the relative operative risk. METHODS: Data were
      gathered through the American College of Surgeons-National Surgical Quality
      Improvement Program (ACS-NSQIP) Pancreatectomy Demonstration Project. Over 14
      months, 822 patients underwent a distal pancreatectomy at 43 institutions. Twenty
      of these patients (2.4%) also underwent a celiac axis resection. DP-CAR patients
      were matched by age, gender, BMI, serum albumin, ASA class, gland texture, duct
      size and pathology to 172 patients undergoing DP alone. RESULTS: The majority of
      DP and DP-CAR patients had adenocarcinomas (61% and 60%). The median operative
      time for a DP alone was shorter than for a DP-CAR (207 versus 276 min, P < 0.01).
      Post-operative acute kidney injury (1% versus 10%, P < 0.03) and 30-day mortality
      were higher after a DP-CAR (1% versus 10%, P < 0.03). CONCLUSION: A distal
      pancreatectomy with celiac axis resection is associated with increased operative
      time, post-operative acute kidney injury and a 10% operative mortality. The
      decision to offer a modified Appleby procedure for a body of pancreas tumour
      should be made with full disclosure of the increased risks.

PMID- 26201996
TI  - Topical dexamethasone gamma-cyclodextrin nanoparticle eye drops increase visual
      acuity and decrease macular thickness in diabetic macular oedema.
AB  - PURPOSE: To compare in a randomized, controlled trial topical 1.5% dexamethasone
      gamma-cyclodextrin nanoparticle eye drops (DexNP) with posterior subtenon
      injection of triamcinolone acetonide in diabetic macular oedema (DME). METHODS:
      In this prospective, randomized, controlled trial, 22 eyes of 22 consecutive
      patients with DME were randomized to (i) topical treatment with DexNP *3/day (4
      weeks), *2/day (4 weeks) and *1/day (4 weeks) or (ii) one posterior subtenon
      injection of 20 mg triamcinolone acetonide. Study visits were at baseline and 4,
      8, 12 and 16 weeks. RESULTS: The logMAR (Snellen) visual acuity (mean +/- SD)
      improved significantly with DexNP from 0.41 +/- 0.3 (Snellen 0.39) to 0.32 +/-
      0.25 (0.48) and 0.30 +/- 0.26 (0.50) at 4 and 8 weeks, respectively. One-third of
      the DexNP group improved more than 0.3 logMAR units. For triamcinolone, logMAR
      changed significantly from 0.42 +/- 0.28 (0.38) at baseline to 0.32 +/- 0.29
      (0.48) at 4w and 0.33 +/- 0.37 (0.47) at 12w. The central macular thickness (CMT)
      decreased significantly with DexNP from 483 +/- 141 MUm to 384 +/- 142 MUm at 4w
      and 342 +/- 114 MUm at 8w. For triamcinolone, CMT decreased significantly at all
      time-points: 494 +/- 94 MUm, 388 +/- 120, 388 +/- 145, 390 +/- 136 and 411 +/-
      104 MUm at 0, 4, 8, 12 and 16 weeks, respectively. There was a modest increase in
      intraocular pressure (IOP) at all time-points with DexNP while no increase was
      seen with triamcinolone. Serum cortisol was affected by both treatments.
      CONCLUSION: Topical DexNP significantly improve visual acuity and decrease
      macular thickness in patients with DME. The effect is similar to that from
      subtenon triamcinolone. A modest increase in IOP was seen with the nanoparticle
      eye drops, but IOP normalized after the discontinuation of treatment.

PMID- 26201997
TI  - Evolution from Stroke Risk Factors to Brain Health Determinants.

PMID- 26201998
TI  - One Dimensional Graphitic Carbon Nitrides as Effective Metal-Free Oxygen
      Reduction Catalysts.
AB  - To explore the effect of morphology on catalytic properties of graphitic carbon
      nitride (GCN), we have studied oxygen reduction reaction (ORR) performance of two
      different morphologies of GCN in alkaline media. Among both, tubular GCN react
      with dissolved oxygen in the ORR with an onset potential close to commercial
      Pt/C. Furthermore, the higher stability and excellent methanol tolerance of
      tubular GCN compared to Pt/C emphasizes its suitability for fuel cells. 

PMID- 26201999
TI  - Predictors of poor-quality spirometry in two cohorts of older adults in Russia
      and Belgium: a cross-sectional study.
AB  - BACKGROUND: Spirometry is an important test for the diagnosis of respiratory
      diseases, yet it is underused especially in older adults. Several predictors of
      good-quality spirometry in this age group have been reported, based mainly on
      in/outpatients of geriatric and/or respiratory units. AIMS: This study aims to
      assess predictors of poor-quality spirometry in community-dwelling older adults
      from two primary care cohorts in Russia and Belgium. METHODS: Spirograms from two
      population-based cohort studies in Russia (CRYSTAL) and Belgium (BELFRAIL) were
      assessed in accordance with the American Thoracic Society/European Respiratory
      Society (ATS/ERS) acceptability and repeatability criteria and grouped into good
      and poor quality. Multivariable analysis assessed the association of poor-quality
      spirometry with socio-demographics, functional dependency, physical and mental
      functioning and co-morbidities. RESULTS: In all, 43.3% of the 522 BELFRAIL
      participants (84.71 +/- 3.67 years old) and 57.7% of the 605 CRYSTAL participants
      (75.11 +/- 5.97 years old) achieved all ATS/ERS acceptability and repeatability
      criteria. In both cohorts, those with poor-quality spirometry had lower cognitive
      function (mini-mental state examination (MMSE) ? 24). After adjustment in
      multivariable analysis, MMSE ? 24 had an odds ratio for poor-quality spirometry
      of 1.33 (95% CI = 0.78-2.28) in the BELFRAIL and 1.30 (95% CI = 0.88-1.91) in the
      CRYSTAL cohort. CONCLUSIONS: In community-dwelling older adults, including those
      over 80 years old, impaired cognition measured by the MMSE may not be an
      independent predictor of poor-quality spirometry. Further research is needed in
      this area, and spirometry should be used more often in older adults in primary
      care.

PMID- 26202001
TI  - Mapping and Ablation of Rotors: Exploring New Frontiers in Treatment of
      Ventricular Fibrillation.

PMID- 26202000
TI  - High-level secretion of human bikunin from recombinant Pichia pastoris.
AB  - Human bikunin is a glycoprotein that exhibits trypsin inhibitory activity against
      serine proteases, and is effective in clinic. However, limited productivity and
      high price of human bikunin retard its further application. In this study, a high
      yield, low-cost process of recombinant human bikunin (rh-bikunin) production from
      Pichia pastoris was established. The trypsin inhibitory activity reached 6.2 *
      10(3)  IU ml(-1) after 120 h induction of P. pastoris fermentation process, which
      was 20-fold higher than that of the previous yield. Furthermore, a simple and low
      cost purification process, including ammonium sulphate precipitation, anion
      exchange adsorption of impurity and cation exchange chromatography, was developed
      with the results of 38.7% recovery and 96.6% purity of rh-bikunin. This work made
      a big step to improve bikunin further application in clinic. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study demonstrated the highest rh-bikunin production
      process towards its application as trypsin inhibitor in clinic. In this work,
      Pichia pastoris GS115 was used as a host for higher rh-bikunin production which
      was 20-fold higher than that of P. pastoris X-33. Then, a simple, low-cost
      purification procedure of rh-bikunin was developed. This potential high
      productivity and low cost of rh-bikunin process will benefit patients eventually.

PMID- 26202002
TI  - Tailored therapy for the refractory GERD patients by combined multichannel
      intraluminal impedance-pH monitoring.
AB  - BACKGROUND AND AIMS: About 30% of patients with gastroesophageal reflux disease
      (GERD) are refractory to proton pump inhibitor (PPI). The reason for the PPI
      failure in Asian GERD patients has rarely been studied, and the therapy remained
      unclear. The aims were to explore the possible reasons for PPI failure and to
      treat these patients with the guidance of 24-h multichannel intraluminal
      impedance-pH (MII-pH) monitoring. METHODS: Thirty-nine consecutive patients with
      refractory GERD were enrolled; 24-h MII-pH monitoring was performed on PPI. The
      refractory GERD patients were grouped into acid overexposure, non-acid reflux,
      and functional heartburn after the MII-pH monitoring. Double dose of either PPI
      or paroxetine was administered to refractory GERD patients within different
      groups. RESULTS: The number of patients in groups of acid overexposure, non-acid
      reflux, and functional heartburn was 6, 12, and 21, respectively. The acid
      overexposure group had the most acid reflux events. Among the acid overexposure
      group, five (5/6) patients accomplish symptom relief with double dose of
      esomeprazole. For the patients in non-acid reflux group, double dose of
      esomeprazole made half (6/12) of the patients obtain symptom relief. For the
      patients in functional heartburn group, the paroxetine had relieved the symptoms
      in 14 patients among all the 21 patients. In total, with the guidance of MII-pH
      monitoring, 64.1% (25/39) of refractory GERD patients accomplished symptom
      relief. CONCLUSIONS: Acid overexposure, non-acid reflux, and functional heartburn
      were the common reasons for persistent reflux symptoms despite PPI. With the
      guidance of MII-pH, a tailored therapy could resolve the persistent reflux
      symptoms among two-third of patients.

PMID- 26202004
TI  - Liver transplantation for cholangiocarcinoma.

PMID- 26202003
TI  - Fatigue screening in breast cancer patients: identifying likely cases of cancer
      related fatigue.
AB  - OBJECTIVE: For clinical and research purposes, efficient identification of cases
      of cancer-related fatigue (CRF) is important, as CRF can be persistent and
      interfere with usual functioning. While various fatigue-screening instruments are
      available, no brief screening indices have been developed using formally
      diagnosed CRF cases as the criterion. METHODS: Breast cancer patients (n = 385)
      completed a fatigue diagnostic interview and self-report fatigue measures
      (Profile of Mood States-fatigue subscale, Fatigue Symptom Inventory, and SF-36
      vitality subscale), after initial adjuvant therapy (post-treatment (post-Tx) 1
      assessment), after completion of radiotherapy for women receiving chemotherapy +
      radiotherapy (post-Tx 2 assessment), and 6 months after completion of all
      adjuvant therapy (6-month post-Tx assessment). CRF cases were identified using
      specific diagnostic criteria. ROC analyses identified screening indices, which
      could accurately identify CRF cases after initial adjuvant therapy. Screening
      indices were cross-validated using post-Tx 2 and 6-month follow-up assessment
      data. RESULTS: A total of 104 women (27%) met CRF criteria after initial adjuvant
      therapy. Six two-item screening indices were identified. For all indices, area
      under the curve exceeded 0.80, sensitivity exceeded 0.80, and specificity
      exceeded 0.57. Cross-validation suggested that, except for the index based on SF
      36, all the indices continued to accurately identify CRF cases at the post-Tx 2
      and 6-month post-Tx assessments. Overall, a two-item composite index based on
      Fatigue Symptom Inventory 'most severity' and 'work interference' items performed
      best. CONCLUSIONS: Breast cancer patients and survivors meeting CRF diagnostic
      criteria can be accurately identified using brief screening indices derived from
      common self-report fatigue measures.

PMID- 26202005
TI  - Here comes the sun.

PMID- 26202006
TI  - Temporary erectile dysfunction after prostate biopsy.

PMID- 26202007
TI  - Prediction and predicament: complications after inguinal lymph node dissection
      for penile cancer.

PMID- 26202008
TI  - Specialty within a specialty: posterior urethroplasty.

PMID- 26202009
TI  - Robotic networks: delivering empowerment through integration.

PMID- 26202010
TI  - Exercise, diet and weight loss before therapy for lower urinary tract
      symptoms/benign prostatic hyperplasia?

PMID- 26202011
TI  - Cardiac microRNA-133 is down-regulated in thyroid hormone-mediated cardiac
      hypertrophy partially via Type 1 Angiotensin II receptor.
AB  - Elevated thyroid hormone (TH) levels induce cardiac hypertrophy partially via
      type 1 Angiotensin II receptor (AT1R). MicroRNAs (miRNAs) are key regulators of
      cardiac homeostasis, and miR-133 has been shown to be involved in cardiac
      hypertrophy. However, the potential role of miR-133 in cardiac growth induced by
      TH is unknown. Thus, we aimed to investigate the miR-133 expression, as well as
      its potential role in cardiac hypertrophy in response to TH. Wistar rats were
      subjected to hyperthyroidism combined or not with the AT1R blocker. T3 serum
      levels were assessed to confirm the hyperthyroid status. TH induced cardiac
      hypertrophy, as evidenced by higher cardiac weight/tibia length ratio and alpha
      actin mRNA levels, which was prevented by AT1R blocker. miR-133 expression was
      decreased in TH-induced cardiac hypertrophy in part through the AT1R.
      Additionally, the cardiac mRNA levels of miR-133 targets, SERCA2a and calcineurin
      were increased in hyperthyroidism partially via AT1R, as evaluated by real-time
      RT-PCR. Interestingly, miR-133 levels were unchanged in T3-induced cardiomyocyte
      hypertrophy in vitro. However, a gain-of-function study revealed that miR-133
      mimic blunted the T3-induced cardiomyocyte hypertrophy in vitro. Together, our
      data indicate that miR-133 expression is reduced in TH-induced cardiac
      hypertrophy partially by the AT1R and that miR-133 mimic prevents the
      cardiomyocyte hypertrophy in response to T3 in vitro. These findings provide new
      insights regarding the mechanisms involved in the cardiac growth mediated by TH,
      suggesting that miR-133 plays a key role in TH-induced cardiomyocyte hypertrophy.

PMID- 26202012
TI  - Phosphatidylglycerol Flip-Flop Suppression due to Headgroup Charge Repulsion.
AB  - The kinetics and thermodynamics of 1,2-distearoyl-sn-glycero-3-[phospho(1'-rac
      glycerol)] (DSPG) flip-flop in 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
      membranes were examined by sum-frequency vibrational spectroscopy (SFVS). The
      effect of DSPG concentration in the membrane and the influence of electrolyte
      concentration were examined in an attempt to decipher the role the anionic PG
      headgroup plays in dictating the dynamics of PG flip-flop for this biologically
      important lipid species. DSPG flip-flop dynamics and the activation barrier to
      exchange were found to be directly dependent on the amount of DSPG present in the
      bilayer. Analysis of the activation free energy for DSPG flip-flop in mixed DSPG
      + DSPC bilayers reveals that charge repulsion between neighboring PG headgroups
      modulates the free energy barrier and subsequently, the rate of translocation.
      Specifically, when DSPG comprises a small portion of the bilayer, the
      electrostatic potential of neighboring PG lipids are effectively shielded from
      each other under high ionic strength conditions and little to no charge repulsion
      occurs. When DSPG lipids are close enough to experience charge repulsion from
      neighboring PG lipids, as in bilayers containing a large fraction of DSPG, or for
      bilayers in low ionic strength solutions, the influence of charge repulsion on
      the energetics of lipid flip-flop are measurable. For biological membranes, where
      the concentration of PG is relatively low, the neighboring PG lipids are spaced
      far enough apart that their anionic charges are effectively shielded, such that
      under physiological conditions the charged nature of the headgroup does little to
      modulate its lipid flip-flop energetics and corresponding rate of translocation. 

PMID- 26202013
TI  - Long-term hormonal follow-up after human Puumala hantavirus infection.
AB  - OBJECTIVE: Nephropathia epidemica (NE) is a haemorrhagic fever with renal
      syndrome (HFRS) caused by Puumala hantavirus (PUUV). Pituitary haemorrhage and
      hypopituitarism may complicate recovery from acute NE. DESIGN: Forty-seven of our
      recent cohort of 58 NE patients volunteered to be re-examined in order to
      estimate the burden of hormonal deficiency 4 to 8 years after the acute illness.
      Two patients had suffered from pituitary haemorrhage, but many others exhibited
      pituitary oedema during their acute infection. In this study, we searched for
      symptoms of hormonal deficiency, performed hormonal laboratory screening, and
      most patients underwent pituitary MRI examination. RESULTS: The pituitary size
      had diminished in all patients in whom MRI was performed (P < 0.001). One patient
      with acute phase haemorrhage had made a complete recovery while the other
      continued to require hormonal substitution. In addition, hormonal laboratory
      abnormalities were observed in nine other patients; these being attributable to
      several reasons, for example independent peripheral hormonal diseases, side
      effects of medication or other secondary causes such as obesity. None of them had
      signs of late-onset pituitary insufficiency caused by their previous NE. Health
      related quality of life (mean and median 15D score) of patients was comparable to
      that of age-standardized general population. CONCLUSIONS: None of our patients
      had developed obvious late-onset hypopituitarism despite of the fact that
      pituitary gland can be affected during acute NE. We recommend requesting a
      history of hantavirus infection whenever the possibility of pituitary dysfunction
      is suspected at least in patients originating from regions with high NE infection
      rate.

PMID- 26202014
TI  - Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase
      Inhibitor Drug Resistance.
AB  - Acquired resistance to therapy is perhaps the greatest challenge to effective
      clinical management of cancer. With several inhibitors of the mitotic checkpoint
      kinase MPS1 in preclinical development, we sought to investigate how resistance
      against these inhibitors may arise so that mitigation or bypass strategies could
      be addressed as early as possible. Toward this end, we modeled acquired
      resistance to the MPS1 inhibitors AZ3146, NMS-P715, and CCT251455, identifying
      five point mutations in the kinase domain of MPS1 that confer resistance against
      multiple inhibitors. Structural studies showed how the MPS1 mutants conferred
      resistance by causing steric hindrance to inhibitor binding. Notably, we show
      that these mutations occur in nontreated cancer cell lines and primary tumor
      specimens, and that they also preexist in normal lymphoblast and breast tissues.
      In a parallel piece of work, we also show that the EGFR p.T790M mutation, the
      most common mutation conferring resistance to the EGFR inhibitor gefitinib, also
      preexists in cancer cells and normal tissue. Our results therefore suggest that
      mutations conferring resistance to targeted therapy occur naturally in normal and
      malignant cells and these mutations do not arise as a result of the increased
      mutagenic plasticity of cancer cells.

PMID- 26202015
TI  - New "haploid biofilm model" unravels IRA2 as a novel regulator of Candida
      albicans biofilm formation.
AB  - Clinical isolates of the fungal human pathogen Candida albicans are invariably
      diploid and heterozygous, impeding genetic study. Recent isolation of C. albicans
      haploids opens opportunities to apply technologies unfeasible in diploids.
      However, doubts remain on whether the haploids, derived from chromosome loss, can
      represent the diploids. Here, we use C. albicans haploids to investigate biofilm,
      a key virulence attribute. We conducted the first comprehensive characterization
      of biofilm formation of the haploids in comparison with the diploids. We
      demonstrate that the haploids form biofilms with essentially the same
      characteristics as the diploids. Screening a haploid mutant library has uncovered
      novel GTPase-related genes as biofilm regulators, including IRA2 that encodes an
      activator of the Ras GTPase. IRA2-deletion mutants develop poorly constructed
      biofilm in both haploid and diploid C. albicans. Our results demonstrate that the
      haploids are a valid model for C. albicans biofilm research and a powerful tool
      for uncovering novel regulators. 

PMID- 26202016
TI  - A new method for achieving compression in hindfoot arthrodesis.
AB  - BACKGROUND: When performing hindfoot arthodeses, one goal of fixation is often to
      achieve compression across the joint. Traditional lag screws are applied
      eccentrically, providing compression more on the edge of the fusion. A new
      technique, using a post in one bone and a lag screw through the post to the other
      bone, may offer better compression across more of the joint. METHODS: There are
      three parts to this study comparing a post-and-screw construct to traditional lag
      screws. Synthetic bone models, representative of the talonavicular joint, were
      created and assessed for biomechanical measures of compression. Next, the post
      and-screw construct was tested in cadavers, under conditions representing early
      weight bearing after arthrodesis surgery. Finally, 18 patients who had a
      talonavicular fusion with a post-and-screw construct with one surgeon were
      compared to the previous 18 patients fixed with traditional screws. RESULTS: In
      the synthetic bone model, the post-and-screw construct brought the centre of
      compression closer to the centre of the joint, suggesting compression was less
      eccentric. Neither traditional screws nor the post-and-screw construct were
      sufficiently strong to resist early weight bearing forces in cadaver specimens.
      In the clinical comparison, four patients had a painful nonunion when fixed with
      traditional screws, compared to none in the post-and-screw construct.
      CONCLUSIONS: A post-and-screw construct spreads the forces of compression more
      uniformly across an arthrodesis, even when placed eccentrically. Although not all
      the biomechanical measures were superior, the post-and-screw construct achieved
      higher levels of successful fusion in patients. This technology may offer
      improved outcomes in some clinical scenarios and deserves further study. LEVEL OF
      EVIDENCE: Level 3.

PMID- 26202017
TI  - Surgical versus conservative treatment of primary patellar dislocation. A
      systematic review and meta-analysis.
AB  - PURPOSE: The purpose of this study was to determine the efficacy of surgical and
      conservative treatment in the prevention of recurrence after primary patellar
      dislocation. METHODS: Studies were searched on MEDLINE, EMBASE, Cochrane Central
      Register of Controlled Trials and CINHAL from their inception to April 2015. All
      randomized controlled clinical trials comparing surgical versus conservative
      treatment after first patellar dislocation were included. Primary outcomes were:
      recurrent dislocation, subluxation, overall instability and subsequent surgery.
      Secondary outcomes included imaging, and subjective and objective clinical
      assessment tools. Methodological quality of the studies was assessed using
      Cochrane Collaboration's "Risk of Bias" tool. Pooled analyses were reported as
      risk ratio (RR) using a random effects model. Continuous data were reported as
      standardized mean difference (SMD) and 95 % confidence intervals (CIs).
      Heterogeneity was assessed using I2. RESULTS: Nine studies were included in the
      meta-analyses. Methodological quality of the studies was moderate to low. Meta
      analyses showed that surgical treatment significantly reduces the redislocation
      rate (RR = 0.62; 95% CI = 0.39, 0.98, p = 0.04) and provides better results on
      Hughston VAS score (SMD = -0.32; 95% CI = -0.61, -0.03; p = 0.03) and running (OR
      = -0.52; 95% CI = 0.31, 0.88; p = 0.01). Conservative treatment showed less
      occurrence of minor complications (OR = 3.46; 95% CI = 2.08, 5.77; p = 0.01) and
      better results in the figure-of-8 run test (SMD = 0.42; 95% CI = 0.06, 0.77; p =
      0.02) and in the squat down test (SMD = -0.45; 95% CI = -0.81, -0.10; p <
      0.00001). No other significant differences could be found. CONCLUSIONS: Based on
      the available data, surgical treatment of primary patella dislocation
      significantly reduces the risk of patella redislocation.

PMID- 26202018
TI  - Surgical result of plate osteosynthesis using a locking plate system through an
      anterior humeral approach for distal shaft fracture of the humerus that occurred
      during a throwing motion.
AB  - PURPOSE: This paper analyzed outcomes of the osteosynthesis with a locking plate
      system for the fractures of the humerus in throwers using the anterior humeral
      approach. METHODS: Retrospective case series including 31 patients. Bone union
      was assessed through follow-up radiographs. Results of visual analogue scale
      (VAS) for pain, range of motion in the elbow joint, time of return to work, and
      the Mayo Elbow Performance Score (MEPS) were evaluated to determine functional
      outcomes. Direction and length of the fracture, the distal cortical length, the
      humeral diameter, and the total humeral length were measured as part of fracture
      configuration analysis. RESULTS: Mean patient age was 25.8 (range, 18-34) years.
      The follow-up average was 16.0 months (range, 12-23). Delayed union was observed
      in one (3.1 %) patient. Mean final VAS was 0.4 (range, 0-2), mean time of return
      to work was 18.2 weeks (range, 13-36), and mean MEPS was 96.3 (range, 88-100)
      points. All fractures showed a spiral configuration. Mean fracture length was
      79.7 (95 % CI, 72.6-86.7) mm, and mean distal cortical length was 48.3 (95 % CI,
      37.8-58.8) mm. CONCLUSIONS: The results of the current study indicates that plate
      osteosynthesis using a locking plate system combined with interfragmentary lag
      screws through anterior humeral approach may be a favorable option for the
      surgical treatment of humeral shaft fractures in throwers.

PMID- 26202019
TI  - Reverse shoulder prosthesis in patients with rheumatoid arthritis: a systematic
      review.
AB  - PURPOSE: To obtain detailed information on the outcomes of patients with
      rheumatoid arthritis (RA) undergoing reverse shoulder arthroplasty (RSA) METHODS:
      A literature search was conducted for studies reporting on the use of RSA in RA
      patients from 1990 to 2014. The inclusion criteria were a report of sufficient
      information on pre-operative status and surgical outcome allowing evaluation of
      the therapeutic potential of RSA in RA. The literature search resulted in 586
      hits, but only five studies that met the inclusion criteria were assessed.
      RESULTS: There were 100 shoulders that had been operated on, of which 87 were
      followed for a mean of 55.4 months, the longest follow-up being 11.9 years Most
      patients had glenohumeral erosive lesions of Larsen Grade III or IV. The Delta
      III prosthesis was implanted in most cases and in three studies bone graft was
      used for severe glenoid lesions. The main outcome measures employed were the
      Constant score (Cs) and ASES questionnaire. The mean increase in Cs and ASES
      score after surgery was 42.4 and 54 points, respectively. The mean post-operative
      forward elevation was 120.6 degrees , the average increment being 51 degrees  and
      the mean increase of abduction was 58.5 degrees . The mean prevalence of scapular
      notching was 35.4 %. The rate of adverse events was 31 %, but the vast majority
      were of minor severity. Eight prostheses underwent revision, due to infection in
      four. CONCLUSIONS: RSA implanted in RA patients would appear to give similar
      results to those obtained in massive cuff tears with or without arthropathy.

PMID- 26202020
TI  - Measuring femoral neck torsion angle using femoral neck oblique axial computed
      tomography reconstruction.
AB  - PURPOSE: To propose a novel method for measuring the femoral neck torsion angle
      (FNTA) with femoral neck oblique axial computed tomography (CT) reconstruction.
      METHODS: Fifty-five patients (24 females, 31 males; mean age 48.8 years [range,
      20-91 years]) were included in the study. CT scans were performed on the left
      femurs of 27 patients and the right femurs of the remaining 28 patients. The
      images were analyzed independently by two observers using oblique axial femoral
      neck CT reconstruction. Intra-observer and inter-observer agreement was
      calculated as intraclass correlation coefficient (ICC). RESULTS: FNTA can be
      measured with high intra-observer (ICC = 0.961) and high inter-observer (ICC =
      0.982) agreement. Mean FNTA was slightly larger in women than in men, and the
      mean left FNTA was slightly larger than the right, but neither difference was
      statistically significant. CONCLUSIONS: Femoral neck oblique axial CT
      reconstruction can be used to obtain accurate measurement of FNTA with good
      reproducibility. No significant differences were found in FNTA between sexes or
      sides.

PMID- 26202021
TI  - The effect of acetabular and femoral component version on dislocation in primary
      total hip arthroplasty.
AB  - PURPOSE: The purpose of the present study was to: (1) investigate the variation
      of both acetabular and femoral component version in a large series of consecutive
      primary THA patients, and (2) to better define the associations of acetabular and
      femoral component alignment and clinical factors with subsequent hip dislocation
      in those patients. METHODS: We analyzed CT scans of 1,555 consecutive primary
      THAs and measured version of the components. We also documented the frequency and
      direction of subsequent dislocation as well as femoral head size, posterior
      tissue repair, any history of previous hip surgery, and gender. RESULTS: The
      dislocation rate after THA was 3.22 %. The dislocation risk was 1.9 times higher
      if cup anteversion was not between 10 degrees  and 30 degrees . Compared to hips
      that did not dislocate, those that experienced anterior dislocation had a
      significantly greater combined anteversion; those that dislocated posteriorly had
      a significantly smaller combined anteversion. Hips with previous rotational
      acetabular osteotomy or head size smaller than 28 mm correlated with an increased
      dislocation rate. CONCLUSION: The dislocation risk could be higher if cup
      anteversion was not between 10 degrees  and 30 degrees . Greater combined
      anteversion could be a risk factor of anterior dislocation, and posterior
      dislocation could be more common in smaller combined anteversion.

PMID- 26202022
TI  - p53 family members - important messengers in cell death signaling in photodynamic
      therapy of cancer?
AB  - TP53 is one of the genes most frequently inactivated in cancers. Mutations in
      TP53 gene are linked to worse prognosis and shorter overall survival of cancer
      patients. TP53 encodes a critical tumor suppressor, which dictates cell fate
      decisions upon stress stimuli. As a sensor of cellular stress, p53 is a relevant
      messenger of cell death signaling in ROS-driven photodynamic therapy (PDT) of
      cancer. The significant role of p53 in response to PDT has been reported for
      several clinically approved photosensitizers. Multiple reports described that
      wild-type p53 contributes to cell killing upon photodynamic therapy with
      clinically approved photosensitizers but the mechanism is still not fully
      understood. This work outlines the diverse functions of p53 family members in
      cancer cells' susceptibility and resistance to PDT. In summary p53 and p53 family
      members are emerging as important mediators of cell death signaling in
      photodynamic therapy of cancer, however the mechanism of cell death provoked
      during PDT might differ depending on the tissue type and the photosensitizer
      applied. 

PMID- 26202023
TI  - Viral factors and outcome of chronic hepatitis B revisited.

PMID- 26202024
TI  - The prediction of immunological dysfunction during antiviral therapy for HCV
      after liver transplantation: can we improve outcomes?

PMID- 26202025
TI  - Human parenchymal and non-parenchymal liver cell isolation, culture and
      characterization.
AB  - Many reports describing parenchymal liver cell isolation have been published so
      far. However, recent evidence has clearly demonstrated that non-parenchymal liver
      cells play an important role in many pathophysiologies of the liver, such as drug
      induced liver diseases, inflammation, and the development of liver fibrosis and
      cirrhosis. In this study, we present an overview of the current methods for
      isolating and characterizing parenchymal and non-parenchymal liver cells. 

PMID- 26202026
TI  - Angiogenesis in liver regeneration and fibrosis: "a double-edged sword".
AB  - Angiogenesis, defined as the formation of new microvasculature from preexisting
      blood vessels and mature endothelial cells, plays a major role in wound healing
      and scar formation, and it is associated with inflammatory responses.
      Angiogenesis can occur in physiological conditions, such as during liver
      regeneration, and in pathological situations, such as during the progression of
      fibrosis to cirrhosis and also during tumor angiogenesis. Cellular cross-talk
      among liver sinusoidal endothelial cells (LSECs), hepatic stellate cells and
      hepatocytes is believed to play an important role in the angiogenesis process
      during both liver regeneration and development of cirrhosis. In addition to
      mature endothelial cells, bone marrow (BM)-derived circulating endothelial
      progenitor cells (EPCs) have been recently identified for their contribution to
      post-natal vasculogenesis/angiogenesis. In vivo, EPCs are mobilized into the
      peripheral blood in response to tissue ischemia or traumatic injury, migrate to
      the sites of injured endothelium and differentiate into mature endothelial cells.
      In our recent studies, we have explored the role of EPC-mediated angiogenesis in
      liver regeneration and/or cirrhosis. Results have demonstrated significantly
      increased endogenous levels of circulating EPCs in cirrhotic patients in
      comparison to the controls. Also, EPCs from cirrhotic patients have been observed
      to stimulate substantial angiogenesis by resident LSECs in vitro via paracrine
      factors such as vascular endothelial growth factor and platelet-derived growth
      factor. This review gives an overview of the angiogenesis process in liver
      regeneration and disease and discusses a new mechanism for intrahepatic
      angiogenesis mediated by BM-derived EPCs. 

PMID- 26202027
TI  - HBsAg, HBeAg and HBV DNA level changes and precore/basal core promoter mutations
      in the natural history of chronic hepatitis B in Indonesian patients.
AB  - INTRODUCTION: Chronic hepatitis B (CHB) is a state of complex interactions
      between the hepatitis B virus (HBV) and host. We studied the changes in hepatitis
      B surface antigen (HBsAg), hepatitis B 'e' antigen (HBeAg) and HBV DNA levels,
      considering the implications of HBV genotype, basal core promoter (BCP)
      A1762T/G1764A and precore G1896A mutations in CHB. METHODS: One hundred fifty-two
      treatment-naive CHB patients were classified into immune-tolerant (IT), immune
      clearance (IC), low/non-replicative (LR) and 'e'-negative hepatitis B (ENH)
      phases, based on HBeAg status, HBV DNA and ALT levels. HBV DNA was detected and
      quantified by polymerase chain reaction, then analyzed by sequencing. HBsAg and
      HBeAg levels were measured serologically. RESULTS: HBsAg and HBV DNA levels
      varied between CHB phases, with HBsAg highest in IT and lowest in LR, and HBV DNA
      high in IT and IC, and lowest in LR. Both markers increased in ENH. Correlation
      between HBsAg and HBV DNA was significant in IT and IC, modest in ENH, but
      missing in LR. HBeAg and HBV DNA levels were dissociated in HBeAg-positive
      patients. Genotypes B and C were similarly distributed, with precore mutations
      higher in HBeAg-negative patients and BCP mutations comparable in all phases.
      Temporal association between HBeAg seroconversion and an increase of BCP/precore
      mutations was observed. CONCLUSION: HBsAg and HBV DNA levels were high and
      correlated in early CHB phases and dissociated after HBeAg seroconversion,
      indicating different controls affecting HBV replication and HBsAg production.
      Selection of BCP/precore mutants may affect disease course and explain the HBeAg
      HBV DNA dissociation, a precaution for clinical application of quantitative
      HBeAg.

PMID- 26202028
TI  - Therapeutic potential of a combined hepatitis B virus surface and core antigen
      vaccine in patients with chronic hepatitis B.
AB  - PURPOSE: The safety and clinical efficacy of a vaccine containing both hepatitis
      B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (HBsAg/HBcAg) were
      evaluated in patients with chronic hepatitis B (CHB). METHODS: Eighteen patients
      with CHB were administered a vaccine containing 100 MUg of HBsAg and 100 MUg of
      HBcAg. The vaccine was administered ten times at 2-weekly intervals, the first
      five times via the nasal route only and the subsequent five times via both nasal
      and subcutaneous routes. The safety and efficacy of this therapeutic approach
      were assessed by periodic assessment of the patients' general condition, viral
      kinetics, and biochemical parameters during treatment and 24 and 48 weeks after
      therapy. The production of cytokines by peripheral blood mononuclear cells (PBMC)
      and antigen-pulsed dendritic cells (DC) was evaluated to assess the
      immunomodulatory effects of the HBsAg/HBcAg vaccine in CHB patients. RESULTS: The
      HBsAg/HBcAg vaccine was safe in all patients. No flare of HBV DNA or alanine
      aminotransferase (ALT) was recorded in any patient. Sustained HBV DNA negativity
      and persistently normalized ALT were detected in 9 (50 %) and 18 (100 %) patients
      with CHB, respectively. PBMC and HBsAg/HBcAg-pulsed DCs from HBsAg/HBcAg
      vaccinated CHB patients produced significantly higher levels of various cytokines
      [interleukin 1beta (IL-1beta), IL-6, IL-8, IL-12, and tumor necrosis factor alpha
      (TNF-alpha)] than those from control unvaccinated CHB patients (p < 0.05) after
      stimulation with HBsAg/HBcAg in vitro. CONCLUSION: HBsAg/HBcAg vaccine seems a
      safe and efficient therapeutic approach for patients with CHB.

PMID- 26202029
TI  - The virological response in Koreans infected with HCV genotype 1 did not differ
      between groups treated with a full dose or reduced dose (>=80 % full dose) of
      peginterferon alfa-2a: a prospective randomized multicenter trial.
AB  - PURPOSE: A high rate of sustained viral response (SVR) in Koreans with chronic
      hepatitis C (CHC) is related to a favorable IL28B genotype. We compared two
      dosing strategies for peginterferon alfa-2a in Koreans with CHC and defined the
      combined effect of polymorphisms and dosing on the virological response. METHODS:
      A total of 178 treatment-naive patients with CHC genotype 1 were prospectively
      enrolled. All patients were randomly assigned to treatment with one of two
      peginterferon alfa-2a regimens: 180 MUg per week for 48 weeks (full-dose group)
      or 180 MUg per week during the first 12 weeks followed by 135 MUg per week for
      the next 36 weeks (dose-reduction group). Polymorphisms related to IL28B, ITPA,
      C20orf194 and SLC29A1 were studied. RESULTS: SVR rates did not differ between the
      full-dose and dose-reduction groups (56.5 and 51.2 %, respectively, p = 0.474).
      The frequency of additional reductions of the peginterferon dose because of
      adverse events was higher in the full-dose group than in the dose-reduction
      group. SVR rates in patients homozygous for the IL28B major allele were higher
      than those in patients for the other IL28B alleles. For patients with unfavorable
      IL28B genotypes, SVR was less likely to be achieved in the dose-reduction group
      than in the full-dose group. CONCLUSIONS: In Koreans with HCV genotype 1, the
      virological response to treatment did not differ between a full dose and reduced
      dose (>=80 % of full dose) of peginterferon alfa-2a. However, in the patients
      with unfavorable IL28B genotypes, the full-dose treatment of peginterferon alfa
      2a may be beneficial.

PMID- 26202030
TI  - Incidence and risk factors for surveillance failure in patients with regular
      hepatocellular carcinoma surveillance.
AB  - BACKGROUND: Initial presentation of hepatocellular carcinoma (HCC) at an advanced
      stage in patients under a regular surveillance program is a devastating problem.
      AIMS: We assessed the prevalence and factors associated with this surveillance
      failure. METHODS: A total of 304 HCC patients who received regular surveillance
      were retrospectively reviewed. Surveillance failure was defined when the tumor
      was diagnosed at beyond the Milan criteria. RESULTS: Surveillance failure rate
      was 5.9 %. Macronodular cirrhosis (MC), ultrasonography-only surveillance (US-S)
      and infiltrative tumor type were independent factors associated with surveillance
      failure. The surveillance failure rate was higher in patients with MC (10.3 vs.
      3.2 %, p = 0.022), US-S (14.6 vs. 4.3 %, p = 0.013) and when the tumor was
      infiltrative type (57.1 vs. 2.1 %, p < 0.001). Based on the two baseline factors
      (MC and US-S), the surveillance failure rates were 35.7, 6.8, 5.9 and 2.6 % for
      MC(+)/US-S(+), MC(+)/US-S(-), MC(-)/US-S(+) and MC(-)/US-S(-), respectively (p <
      0.001). CONCLUSION: The HCC surveillance failure was not rare in clinical
      practice. These data suggest that special attention for surveillance failure
      might be needed for patients with MC who receive US-S.

PMID- 26202031
TI  - Familial clustering of hepatocellular carcinoma in HBsAg-positive patients in the
      United States.
AB  - PURPOSE: The impact of familial clustering of hepatocellular carcinoma (HCC) in
      hepatitis B virus (HBV)-infected persons in a low HBV endemic area was
      investigated. METHODS: Four hundred thirteen HBsAg-positive patients, 173 with
      HCC and 240 without HCC, were subgrouped into those with or without a family
      history of HCC and analyzed for risk factors associated with HCC development. In
      families with HCC clustering, the ages of HCC onset in parents and siblings were
      compared. RESULTS: Forty-four of 173 (25.4 %) HCC patients, all of Asian descent,
      had 82 other blood relatives with HCC. Of these, 69 (84.1 %) were first-degree
      relatives. Compared to HCC patients without HCC family history, male HCC patients
      with family history developed HCC at a younger age than either their mothers or
      fathers with HCC (45.2 +/- 10.3 years vs. 63.0 +/- 6.8 years, p < 0.001 and 41.2
      +/- 14.8 years vs. 60.5 +/- 5.5 years, p = 0.001, respectively); however, this
      was not observed in female HCC patients. In mothers of index HCC cases, 22/26
      (84.6 %) tested were HBsAg positive and 14 (63.6 %) had HCC; in fathers, 11/21
      (52.4 %) tested were HBsAg positive and 10 (90.9 %) had HCC. By multivariate
      analysis, independent risk factors for HCC development included family history
      (OR = 2.58, p = 0.05), male gender (OR = 3.23, p = 0.03), cirrhosis (OR = 2.4, p
      = 0.04), Child-Pugh classification (OR = 7.62, p = 0.004), AFP per log10 increase
      (OR = 1.68, p = 0.01), precore mutation (OR = 3.77, p = 0.003), and basal core
      promoter mutation (OR = 8.33, p < 0.001). CONCLUSIONS: HBsAg-positive male HCC
      patients presented at a younger age than their parents with HCC. In adult
      patients with an HCC family history, HCC surveillance should begin at the time of
      the initial clinic encounter.

PMID- 26202032
TI  - Clinical features and natural history of portal vein thrombosis after
      radiofrequency ablation for hepatocellular carcinoma in Japan.
AB  - PURPOSE: Little is known about portal vein thrombosis (PVT) after radiofrequency
      ablation (RFA) for hepatocellular carcinoma (HCC). We aimed to determine the
      incidence, background, and natural history of RFA-related PVT. METHODS: This is a
      retrospective study of 317 patients (219 males and 98 females) with HCC treated
      by RFA. Clinical data were compared between patients with and without PVT
      detected by ultrasound/CT. The median follow-up period after RFA was 15.8 months.
      RESULTS: PVT was detected in 6 (1.9 %) of 317 patients, 6 (0.8 %) of 802
      treatments for HCC, and 6 (0.6 %) of 964 sessions of RFA. Body mass index was
      significantly higher in patients with PVT (26.9 +/- 3.1 kg/m(2)) than in those
      without (22.9 +/- 3.5 kg/m(2), p = 0.0075). PVT was significantly more frequent
      in RFA for the left lobe of the liver (2.7 %) than for the other sites (0 %, p <
      0.0001). Five of the six patients received no treatment for PVT, with natural
      outcomes of disappearance in one patient, improvement in one patient, and
      unchanged appearance in three patients. Anticoagulation was applied in the one
      remaining patient and resulted in a successful recanalization. In the six
      patients, there was no significant difference in hepatic functional reserve
      between baseline and time of detection of PVT. CONCLUSIONS: These results
      indicated that a high body mass index and RFA for HCC in the left lobe might be
      significant risk factors for PVT and that RFA-related PVT was rarely progressive
      with little influence on liver function.

PMID- 26202033
TI  - Elevated ALT and GGT predict all-cause mortality and hepatocellular carcinoma in
      Taiwanese male: a case-cohort study.
AB  - PURPOSE: Evidence indicates a positive association between liver enzymes and the
      risk of death in Western countries; however, the evidence in Asian populations is
      scarce. We investigated the association between liver enzymes and total,
      cardiovascular (CVD), cancer and hepatocellular carcinoma (HCC) mortality in a
      cohort of Taiwanese male free of cancer at baseline. METHODS: From 1996 to 2003,
      54,751 Taiwanese male aged 40-80 years without cancer completed a health
      screening and were followed through 2005 (5.8 +/- 2.5 years of follow-up). A
      random cohort of 3,961 male was selected to compare to 1,864 male who died. We
      used Cox proportional hazards regression models to assess the risk of all-cause,
      cardiovascular and cancer mortality associated with alanine aminotransferase
      (ALT), aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT).
      RESULTS: In this population, higher levels of ALT, AST and GGT were significantly
      associated with all-cause mortality [hazard ratio (HR) 1.2, 1.8 and 1.6 for ALT,
      AST and GGT, respectively; all p < 0.05], cancer mortality (HR 1.8-2.8) and HCC
      mortality (HR 5.5-36.1). GGT was significantly associated with CVD mortality (HR
      1.2). CONCLUSIONS: In Taiwanese male free of cancer at baseline, elevations of
      ALT, AST and GGT were associated with future risk of all-cause death, all cancer
      and HCC mortality, independent of conventional risk factors, and could be used to
      identify male who would benefit from HCC screening.

PMID- 26202034
TI  - Circulating free DNA in the progression of liver damage to hepatocellular
      carcinoma.
AB  - PURPOSE: Circulating free DNA (cfDNA) is an extracellular DNA released in the
      blood by tumor apoptotic/necrotic cells. cfDNA determination has been proposed as
      a non-invasive and sensitive marker in the diagnosis of cancer. Our aim was to
      validate the quantification of cfDNA as a diagnostic and prognostic tool in
      hepatocellular carcinoma (HCC). METHODS: cfDNA was quantified by real-time PCR
      amplification of the hTERT gene in 142 plasma samples obtained from 66 patients
      with HCC, 35 with cirrhosis (CIRR) and 41 with advanced HCV-related chronic
      hepatitis (CH). RESULTS: cfDNA was documented in the plasma of 22 % of the CH
      patients, 57 % of those with CIRR and 61 % of HCC patients. Its concentration was
      lower in CH with respect to CIRR and HCC (p = 0.02). A cutoff value in the
      diagnosis of HCC was calculated by the ROC method (area under the curve 0.69, 91
      % sensitivity, 43 % specificity) considering HCC versus CH/CIRR, taken together.
      Patients with multinodular HCC showed significantly higher levels of cfDNA (p =
      0.05). A cutoff value for cfDNA was also calculated for discriminating patients
      with long or short survival. Survival was significantly longer in patients with
      cfDNA below than in those above the cutoff value (37 vs. 24 months, p = 0.03).
      Similar results were obtained in the subgroups of patients with viral or with HCV
      only etiology, with slightly higher overall diagnostic accuracy. CONCLUSIONS: The
      role of the quantitative analysis of cfDNA as a diagnostic test is debatable, but
      cfDNA levels discriminate patients with more advanced stages of disease,
      demonstrating a prognostic relevance in patients with HCC.

PMID- 26202035
TI  - Value of the APASL severity score in patients with acute variceal bleeding: a
      single center experience.
AB  - BACKGROUND: Acute variceal bleeding is a severe complication in patients with
      cirrhosis. The Asian Pacific Association for Study of the Liver (APASL) severity
      score was proposed in 2011. This score is used for evaluating the severity of
      acute variceal bleeding. However, as this score is largely based on expert
      opinion, it requires validation. AIM: To determine the value of the APASL
      severity score. METHODS: We retrospectively reviewed the medical records of
      patients treated for acute variceal bleeding at Konkuk University Hospital from
      2006 to 2011. The APASL severity score, Child-Pugh score, and Model for End-Stage
      Liver Disease (MELD) score were calculated, and predictive values for treatment
      failure, rebleeding, and in-hospital mortality were compared by the area under
      the receiver operating curve (AUROC). RESULTS: A total of 136 patients were
      enrolled, and all patients were treated by endoscopic variceal ligation (EVL) and
      terlipressin combination therapy. Most patients were male (n = 123, 90.4 %), and
      the most common etiology was alcohol (n = 91, 66.9 %). Thirteen treatment
      failures, eight rebleedings, and seven in-hospital mortalities occurred. The
      AUROCs of the APASL severity score, Child-Pugh score, and MELD score were 0.760,
      0.681, and 0.607 for treatment failure; 0.660, 0.714, and 0.677 for rebleeding;
      and 0.872, 0.847, and 0.735 for in-hospital mortality. A significant difference
      was only observed between the APASL severity score and MELD score for treatment
      failure (p = 0.0259). CONCLUSION: APASL severity score was a useful method for
      predicting treatment failure. However, the predictive value for rebleeding and in
      hospital mortality were not satisfactory.

PMID- 26202036
TI  - Hedgehog signaling influences gender-specific response of liver to radiation in
      mice.
AB  - BACKGROUND: It is unclear why the response to radiation in the female liver is
      different from that of the male liver. Hedgehog (Hh) that remains latent in
      healthy adult livers is activated in the injured liver and promotes the
      proliferation of progenitors and myofibroblastic hepatic stellate cells, leading
      to hepatic fibrosis. OBJECTIVE: These findings have led to the hypothesis that
      the gender-specific expression of Hh signaling could affect the different
      response of the female liver to radiation. METHODS: Male and female mice
      irradiated with a single dose of 6 Gy were killed at 1 week post irradiation, and
      the livers were collected for biochemical analysis. RESULTS: A greater
      accumulation of fatty hepatocytes and apoptotic cells was observed in irradiated
      female mice. Sox-9 and pancytokeratin-positive cells were expanded in the livers
      of irradiated female, but not male, mice. The expression of the Hh ligand, Sonic
      Hh, Hh receptor, Smoothened, and Hh-target gene, Gli2, showed a greater increase
      in the liver of radiation-treated female. The levels of epithelial-to-mesenchymal
      transition (EMT)-stimulating factor, transforming growth factor-beta, collagen
      alpha1, and N-cadherin were upregulated, while the EMT inhibitor, bmp7, was
      downregulated in the damaged liver of females compared to controls. In addition,
      increased fibrosis was seen in the injured livers of female mice. No significant
      changes in Hh expression and EMT were detected in the irradiated male mice.
      CONCLUSION: These results demonstrated that the increased expression of Hh
      signaling contributed to the different repair process in the irradiated female
      mice by promoting proliferation of progenitor and EMT process.

PMID- 26202037
TI  - Multiple courses of G-CSF in patients with decompensated cirrhosis: consistent
      mobilization of immature cells expressing hepatocyte markers and exploratory
      clinical evaluation.
AB  - INTRODUCTION: Bone marrow-derived cells (BMCs) include stem cells capable of self
      renewal and differentiation into a variety of cell types. Administration of
      granulocyte colony-stimulating factor (G-CSF) induces the circulation of BMCs in
      the peripheral blood. A phase II prospective trial was carried out for evaluation
      of BMC mobilization induced by multiple courses of G-CSF in cirrhotic patients.
      PATIENTS AND METHODS: Fifteen patients with advanced liver cirrhosis (Child-Pugh
      score >=6 points) were enrolled and treated with a 3-day G-CSF course,
      administered at 3-month intervals for a total of four courses. BMC mobilization
      was assessed by evaluating CD34+ve cells using flow cytometry. Expressions of
      multiple hepatic and stem markers were assessed on mobilized CD34+ve cells.
      Feasibility and safety were explored; clinical and adverse events were compared
      to those of a control group. Telomere length was monitored to rule out early cell
      aging caused by G-CSF. RESULTS: A significant increase in G-CSF-induced
      circulating CD34+ve cells was consistently observed, although a progressive
      reduction of peak values was documented from cycle I to IV (p < 0.005). Mobilized
      CD34+ve cells expressed both stem and multiple hepatocyte markers, including mRNA
      of albumin and CYP2B6 (cytochrome P2 B6). Treatment was well tolerated, with no
      severe adverse events and no significant telomere length shortening following G
      CSF. The procedure was safe. Overall, ten patients had either improved or had
      stable liver function tests (such as the Child-Pugh score), whereas five worsened
      and died from liver-related causes. CONCLUSION: This study demonstrates that G
      CSF can be safely administrated up to four times over a 1-year period in
      decompensated cirrhotic patients. The repeated BMC mobilization favors the
      circulation of stem cells coexpressing hepatic markers and mRNA of liver-related
      genes.

PMID- 26202038
TI  - Hepatocytes of cirrhotic rat liver accumulate glycogen more slowly than normal
      ones.
AB  - PURPOSE: To investigate the accumulation of glycogen in cirrhotic rat liver at
      several time intervals after per os administration of glucose to fasted animals.
      METHODS: Liver cirrhosis was produced by inhalation of the hepatotropic poison
      CCl4. Glycogen concentration in the liver was determined biochemically. Glycogen
      content in hepatocytes was measured cytofluorimetrically in the smears stained
      with a fluorescent PAS reaction. Glycogen content in the hepatocytes of the
      portal and the central zone of the liver lobule was determined by absorption
      cytophotometry. RESULTS: Rats poisoned with CCl4 for 6 months developed typical
      liver cirrhosis characterized by a fourfold (p < 0.001) increase in the
      proportion of the connective tissue. In the cirrhotic rats fasted for 48 h,
      glycogen concentration in the liver and glycogen content in hepatocytes were
      lower as compared with the control by 36 and 27 % (p < 0.01), respectively.
      According to data obtained by different methods, the control animals accumulated
      glycogen at a high rate. In particular, the glycogen content in hepatocytes
      increased by 34 % after 10 min (p < 0.01). In the cirrhotic rats, glycogen
      content remained at the same level for 20 min. In both groups of animals,
      hepatocytes of the portal zone accumulated more glycogen than those of the
      central zone. CONCLUSIONS: Glycogen accumulation in cirrhotic rats starts after a
      delay and proceeds at a lower rate than in the norm.

PMID- 26202039
TI  - Early Workplace Communication and Problem Solving to Prevent Back Disability:
      Results of a Randomized Controlled Trial Among High-Risk Workers and Their
      Supervisors.
AB  - Purpose There is a clear need for interventions that successfully prevent the
      development of disability due to back pain. We hypothesized that an intervention
      aimed at both the worker and the workplace could be effective. Hence, we tested
      the effects of a new early intervention, based on the misdirected problem solving
      model, aimed at both workers at risk of long-term impairments and their
      workplace. Methods Supervisors of volunteers with back pain, no red flags, and a
      high score on a screen (Orebro Musculoskeletal Screening Questionnaire) were
      randomized to either an evidence based treatment as usual (TAU) or to a worker
      and workplace package (WWP). The WWP intervention included communication and
      problem solving skills for the patient and their immediate supervisor. The key
      outcome variables of work absence due to pain, health-care utilization, perceived
      health, and pain intensity were collected before, after and at a 6 month follow
      up. Results The WWP showed significantly larger improvements relative to the TAU
      for work absence due to pain, perceived health, and health-care utilization. Both
      groups improved on pain ratings but there was no significant difference between
      the groups. The WWP not only had significantly fewer participants utilizing
      health care and work absence due to pain, but the number of health care visits
      and days absent were also significantly lower than the TAU. Conclusions The WWP
      with problem solving and communication skills resulted in fewer days off work,
      fewer health care visits and better perceived health. This supports the
      misdirected problem solving model and indicates that screening combined with an
      active intervention to enhance skills is quite successful and likely cost
      effective. Future research should replicate and extend these findings with health
      economic analyses.

PMID- 26202041
TI  - Dedicated NAVA enteral feeding tube placement complicated by a hydropneumothorax
      but producing a correct EAdi signal.

PMID- 26202040
TI  - Regional variation in critical care provision and outcome after high-risk
      surgery.
AB  - PURPOSE: Evidence of variation in mortality after surgery may indicate
      preventable postoperative death. We sought to determine if regional differences
      in outcome were present in surgical patients admitted to critical care in the UK.
      METHODS: We extracted data on admission characteristics, case mix and outcome of
      all patients admitted to UK critical care units following surgery for the
      calendar year of 2009. We also used publicly held data on regional population,
      volume of surgery and bed provision. Multilevel regression analysis was used to
      adjust for the effects of case mix and regional critical care bed provision on
      acute hospital mortality. RESULTS: A total of 16,147 patients admitted to
      critical care following surgery were included in this analysis. Median odds ratio
      (MOR) was used to describe regional-level variance in acute hospital mortality.
      Significant variation was identified (MOR 1.14; 95% CI 1.07, 1.28) and persisted
      following adjustment for case mix (MOR 1.10; 95% CI 1.04, 1.25) and regional
      critical care bed provision (MOR 1.09; 95% CI 1.04, 1.24). Critical care bed
      utilisation (surgical critical care admissions per 100,000 surgical procedures)
      seemed to better explain this observation (MOR 1.03; 95% CI 1.00, 29.26) and was
      associated with statistically significant reduction in mortality (OR 0.91; 95% CI
      0.85, 0.97; p = 0.01). CONCLUSION: Significant regional variation in hospital
      mortality for patients admitted to critical care following surgery was observed.
      Critical care bed utilisation seemed to better explain this observation and was
      associated with improved outcome.

PMID- 26202042
TI  - Respective impact of lowering body temperature and heart rate on mortality in
      septic shock: mediation analysis of a randomized trial.
AB  - PURPOSE: We previously showed that external cooling decreases day 14 mortality in
      febrile septic shock. Because cooling may participate in heart rate control, we
      studied the respective impact of heart rate and temperature lowering on
      mortality. METHODS: Post hoc analysis of the Sepsiscool randomized controlled
      trial database (NCT00527007). Cooling was applied to maintain normothermia (36.5
      37  degrees C) during 48 h. We assessed the time spent below different thresholds
      of temperature and heart rate on day 14 mortality. The best threshold was
      selected by AUC-ROC and tested as a potential mediator of mortality reduction.
      Mediation analysis was adjusted for severity and treatments influencing
      temperature and heart rate evolution. Sensitivity analysis was done using only
      patients with appropriate antimicrobial therapy. RESULTS: A total of 197/200
      patients with adequate heart rate and temperature monitoring were analyzed. The
      best threshold differentiating survivors and nonsurvivors was 38.4  degrees C for
      temperature and 95 b/min for heart rate. During the 48 h of intervention, cooling
      significantly increased the time spent with a temperature below 38.4  degrees C,
      p = 0.001, and with a heart rate below 95 b/min, p < 0.01. The longer was the
      time spent with a temperature below 38.4  degrees C, the lower was the mortality
      [adjOR 0.17 (0.06-0.49), p = 0.001]. The time spent with a heart rate below 95
      b/min was similar in survivors and nonsurvivors [adjOR 0.68 (0.27-1.72), p =
      0.42]. Mediation analysis showed that the time spent with a temperature below
      38.4  degrees C was a significant mediator of mortality. CONCLUSION: The time
      spent with a temperature below 38.4  degrees C was independently associated with
      patient's outcome and explained 73% of the effect of the randomization on the day
      14 mortality. Heart rate lowering was not a mediator of mortality.

PMID- 26202043
TI  - External validation confirms the legitimacy of a new clinical classification of
      ARDS for predicting outcome.

PMID- 26202044
TI  - Cushing's syndrome in pregnancy. Laparoscopic adrenalectomy during pregnancy: the
      mainstay treatment.
AB  - INTRODUCTION: Cushing's syndrome (CS) is a rare disease in pregnancy and its
      differential diagnosis is complicated. It is usually confused with complicated
      pregnancy cases, such us preeclampsia and gestational diabetes. This usually
      leads to a delayed diagnosis and is also associated with severe materno-foetal
      complications. PURPOSE: We present a case of a pregnant woman in her third
      trimester of pregnancy with CS secondary to an adrenal adenoma without response
      to medical treatment who underwent laparoscopic adrenalectomy without
      complications. DISCUSSION: Most authors consider adrenalectomy as the first
      choice treatment, since it presents higher rate of successful pregnancies.
      However, previously published cases did not reflect this stance. These
      publications prefer to maintain medical treatment, allowing pregnancy to go to
      term and delaying adrenalectomy after childbirth. We consider that experience in
      laparoscopic surgery, obstetric knowledge and resources now available, all offer
      sufficient guarantees to carry out the laparoscopic procedure to treat CS in
      pregnancy even in the third trimester. Laparoscopic adrenalectomy for CS in
      pregnancy is a safe and efficacious procedure allowing stopping the disease and
      curbing the dreadful consequences it may have for both mother and foetus.

PMID- 26202046
TI  - Examining the Structure of Emotion Regulation: A Factor-Analytic Approach.
AB  - OBJECTIVE: Critiques of self-report indices of emotion regulation suggest that
      its measurement is in need of more critical investigation. The current study
      examined the factor structure of emotion regulation as informed by Gross' (1998a)
      Process Model: Situation Selection, Attentional Deployment, Cognitive Change, and
      Response Modulation. METHOD: A sample of 553 participants was recruited using
      Amazon's Mechanical Turk (M(age) = 37.12, SD = 13.66; n = 352 female).
      Confirmatory factor analysis with maximum likelihood estimation was performed in
      Mplus. RESULTS: A four-factor model of emotion regulation demonstrated poor fit.
      An alternative five-factor model fit the data well: CFI = .94, TLI = .93, RMSEA =
      .07. CONCLUSION: Emotion regulation may be better conceptualized as a combination
      of specific strategy use and a broader construct, called "emotional distancing"
      (a trait-like disposition towards emotions). Further research is required to
      determine if the observed five-factor model can be replicated in more diverse
      samples.

PMID- 26202045
TI  - Acquisition of cancer stem cell-like properties in non-small cell lung cancer
      with acquired resistance to afatinib.
AB  - Afatinib is an irreversible epidermal growth factor receptor (EGFR)-tyrosine
      kinase inhibitor (TKI) that is known to be effective against the EGFR T790M
      variant, which accounts for half of the mechanisms of acquired resistance to
      reversible EGFR-TKIs. However, acquired resistance to afatinib was also observed
      in clinical use. Thus, elucidating and overcoming the mechanisms of resistance
      are important issues in the treatment of non-small cell lung cancer. In this
      study, we established various afatinib-resistant cell lines and investigated the
      resistance mechanisms. EGFR T790M mutations were not detected using direct
      sequencing in established resistant cells. Several afatinib-resistant cell lines
      displayed MET amplification, and these cells were sensitive to the combination of
      afatinib plus crizotinib. As a further investigation, a cell line that acquired
      resistance to afatinib plus crizotinib, HCC827-ACR, was established from one of
      the MET amplified-cell lines. Several afatinib-resistant cell lines including
      HCC827-ACR displayed epithelial-to-mesenchymal transition (EMT) features and
      epigenetic silencing of miR-200c, which is a suppresser of EMT. In addition,
      these cell lines also exhibited overexpression of ALDH1A1 and ABCB1, which are
      putative stem cell markers, and resistance to docetaxel. In conclusion, we
      established afatinib-resistant cells and found that MET amplification, EMT, and
      stem cell-like features are observed in cells with acquired resistance to EGFR
      TKIs. This finding may provide clues to overcoming resistance to EGFR-TKIs.

PMID- 26202047
TI  - Cushing's Syndrome Due to CRH and ACTH Co-secreting Pancreatic Tumor-
      Presentation of a New Case Focusing on Diagnostic Pitfalls.
AB  - Cushing's syndrome (CS) due to a corticotropin-releasing hormone (CRH) and
      adrenocorticotropin hormone (ACTH) co-secreting tumor is very rare, and diagnosis
      can be difficult. We describe a case of CS caused by ectopic CRH and ACTH
      production from a pancreatic neuroendocrine tumor (pNET) and discuss possible
      pitfalls in the diagnosis. A 48-year-old woman presented with gradual increase in
      body weight, muscle weakness, and difficult to control hypertension. Laboratory
      and imaging investigations revealed ACTH-dependent hypercortisolemia and a 3-cm
      mass at the head of the pancreas. The patient underwent partial
      pancreatoduodenectomy. Histological examination revealed a well-differentiated
      pNET, expressing both CRH and ACTH. After a follow-up period of 18 months, she
      remains asymptomatic with no metastatic disease. This is the fourth case report
      of CS in adults due to an ectopic ACTH- and CRH-secreting pNET. Co-secretion of
      ACTH and CRH by the same tumor may cause diagnostic problems since investigation
      depends on which of the two hormones is secreted in greater amounts. Measurement
      of plasma CRH may help in establishing the diagnosis, especially in patients in
      whom endocrine tests are indicative of ectopic CS, whereas imaging findings are
      suggestive of pituitary hyperplasia. 

PMID- 26202048
TI  - Hypertrophic osteoarthropathy presenting as inflammatory arthritis.

PMID- 26202051
TI  - Renal Disease Risk Factors Among Risk Groups Comprised of African American Women
      With Type 2 Diabetes: A Secondary Analysis.
AB  - PURPOSE: The purpose of this study was to explore and describe the prevalence of
      renal disease risk factors and the categorization of renal disease risk groups
      among African American women with type 2 diabetes mellitus (T2DM) who
      participated in a self-management and coping skills training intervention. We
      also explored and described the change in renal disease risk factors within and
      between risk groups, determining if participation in a culturally relevant coping
      skills training intervention decreased renal disease risk. METHODS: This study
      was a secondary analysis of data from a longitudinal intervention study and
      included all 109 African American women with T2DM from the primary intervention
      study. This study examined the prevalence of 4 renal disease risk factors among
      the women at baseline via descriptive statistics, used cluster analysis to divide
      the women into risk groups and categorize the risk groups, and also measured the
      change in risk factors over time among risk groups via mixed modeling. RESULTS: A
      majority of the women had a hemoglobin A1C >=7% (62.39%) and were obese (75.93%).
      The high-risk cluster displayed clinically significant declines in mean systolic
      blood pressure, triglycerides, and A1C in both the control and intervention
      groups, and the intervention was more effective in reducing triglycerides and A1C
      levels among high-risk participants than low-risk. Overall, the control, high
      risk group exhibited the largest declines in systolic blood pressure,
      triglycerides, and A1C. CONCLUSIONS: This study displays the importance of
      acknowledging African American women with type 2 diabetes mellitus (T2DM) at high
      risk for renal disease in health care settings, which is often overlooked, and
      realizing that renal disease risk reduction is obtainable.

PMID- 26202052
TI  - Reduced skeletal muscle quantity and quality in patients with diabetic
      polyneuropathy assessed by magnetic resonance imaging.
AB  - INTRODUCTION: The aim of this study was to determine whether diabetic
      polyneuropathy (DPN) is associated with reduced muscle quality using MRI.
      METHODS: MRIs of the tibialis anterior (TA) muscle were recorded from 9
      individuals (5 men) with DPN (~65 years) and 8 (4 men) age- and gender-matched
      controls. A magnetization transfer ratio (MTR) and T2 relaxation times of the TA
      were calculated. RESULTS: Despite equal voluntary activation, the DPN group was
      ~37% weaker than controls, with a significantly lower proportion (~8%) of
      contractile tissue and lower MTR (0.28 +/- 0.03 vs. 0.32 +/- 0.02 percent units).
      T2 relaxation time was significantly longer in the DPN group (77 +/- 16 ms)
      compared with controls (63 +/- 6 ms). CONCLUSIONS: These findings indicate a
      reduction in the structural integrity and myocellular protein density in the TA
      of those with DPN. Thus, muscle weakness in DPN is likely due to both a loss of
      muscle mass and a reduction in contractile quality.

PMID- 26202053
TI  - Does internal mammary node irradiation affect treatment outcome in clinical stage
      II-III breast cancer patients receiving neoadjuv ant chemotherapy?
AB  - The purpose of this study is to assess the value of internal mammary node
      irradiation (IMNI) in patients receiving postoperative radiotherapy after
      neoadjuvant chemotherapy (NAC) using modern systemic therapy. Between 2001 and
      2009, 521 consecutive patients with clinical stage II-III breast cancer received
      NAC and postoperative radiotherapy. With a consistent policy, the treating
      radiation oncologist either included (N = 284) or excluded (N = 237) the internal
      mammary node in the treatment volume. Anthracycline- and taxane-based
      chemotherapy was provided to 482 (92.5 %) patients. To account for the unbalanced
      characteristics between the two groups, we performed propensity score matching
      and covariate adjustment using the propensity score. The median follow-up
      duration was 71 months (range 31-153 months). The 5-year disease-free survival
      (DFS) with and without IMNI was 81.8 and 72.7 %, respectively (p = 0.019). The
      benefit of IMNI varied according to patient characteristics such that it was more
      apparent in patients with N1-2 disease, inner/central location, and triple
      negative subtype. After adjusting for all potential confounding variables, IMNI
      was independently associated with improved DFS (p = 0.049). The significant
      effect of IMNI on DFS was sustained after propensity score matching (p = 0.040)
      and covariate adjustment using the propensity score (p = 0.048). Symptomatic
      radiation pneumonitis developed in 9 (3.2 %) patients receiving IMNI. Our results
      indicated that IMNI was associated with a significant improvement in DFS with low
      toxicity rate for breast cancer patients receiving NAC. Further prospective
      studies are warranted to confirm the effect of IMNI in the NAC setting.

PMID- 26202050
TI  - Prediction and prevention of type 1 diabetes: update on success of prediction and
      struggles at prevention.
AB  - Type 1 diabetes mellitus (T1DM) is the archetypal example of a T cell-mediated
      autoimmune disease characterized by selective destruction of pancreatic beta
      cells. The pathogenic equation for T1DM presents a complex interrelation of
      genetic and environmental factors, most of which have yet to be identified. On
      the basis of observed familial aggregation of T1DM, it is certain that there is a
      decided heritable genetic susceptibility for developing T1DM. The well-known
      association of T1DM with certain human histocompatibility leukocyte antigen (HLA)
      alleles of the major histocompatibility complex (MHC) was a major step toward
      understanding the role of inheritance in T1DM. Type 1 diabetes is a polygenic
      disease with a small number of genes having large effects (e.g., HLA) and a large
      number of genes having small effects. Risk of T1DM progression is conferred by
      specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3/DQ2) or DRB1*04
      DQB1*0302 (DR4/DQ8)]. In addition, the HLA allele DQB1*0602 is associated with
      dominant protection from T1DM in multiple populations. A concordance rate lower
      than 100% between monozygotic twins indicates a potential involvement of
      environmental factors on disease development. The detection of at least two islet
      autoantibodies in the blood is virtually pre-diagnostic for T1DM. The majority of
      children who carry these biomarkers, regardless of whether they have an a priori
      family history of the disease, will develop insulin-requiring diabetes.
      Facilitating pre-diagnosis is the timing of seroconversion which is most
      pronounced in the first 2 yr of life. Unfortunately the significant progress in
      improving prediction of T1DM has not yet been paralleled by safe and efficacious
      intervention strategies aimed at preventing the disease. Herein we summarize the
      chequered history of prediction and prevention of T1DM, describing successes and
      failures alike, and thereafter examine future trends in the exciting, partially
      explored field of T1DM prevention. 

PMID- 26202054
TI  - Interaction between smoking history and gene expression levels impacts survival
      of breast cancer patients.
AB  - In contrast to studies focused on cigarette smoking and risk of breast cancer
      occurrence, this study explored the influence of smoking on breast cancer
      recurrence and progression. The goal was to evaluate the interaction between
      smoking history and gene expression levels on recurrence and overall survival of
      breast cancer patients. Multivariable Cox proportional hazards models were fitted
      for 48 cigarette smokers, 50 non-smokers, and the total population separately to
      determine which gene expressions and gene expression/cigarette usage interaction
      terms were significant in predicting overall and disease-free survival in breast
      cancer patients. Using methods similar to Andres et al. (BMC Cancer 13:326,
      2013a; Horm Cancer 4:208-221, 2013b), multivariable analyses revealed CENPN,
      CETN1, CYP1A1, IRF2, LECT2, and NCOA1 to be important predictors for both breast
      carcinoma recurrence and mortality among smokers. Additionally, COMT was
      important for recurrence, and NAT1 and RIPK1 were important for mortality. In
      contrast, only IRF2, CETN1, and CYP1A1 were significant for disease recurrence
      and mortality among non-smokers, with NAT2 additionally significant for survival.
      Analysis of interaction between smoking status and gene expression values using
      the combined samples revealed significant interactions between smoking status and
      CYP1A1, LECT2, and CETN1. Signatures consisting of 7-8 genes were highly
      predictive for breast cancer recurrence and overall survival among smokers, with
      median C-index values of 0.8 and 0.73 for overall survival and recurrence,
      respectively. In contrast, median C-index values for non-smokers was only 0.59.
      Hence, significant interactions between gene expression and smoking status can
      play a key role in predicting breast cancer patient outcomes. 

PMID- 26202055
TI  - Gene signature model for breast cancer risk prediction for women with sclerosing
      adenosis.
AB  - Benign breast disease (BBD) is diagnosed in 1-2 million women/year in the US, and
      while these patients are known to be at substantially increased risk for
      subsequent development of breast cancer, existing models for risk assessment
      perform poorly at the individual level. Here, we describe a DNA-microarray-based
      transcriptional model for breast cancer risk prediction for patients with
      sclerosing adenosis (SA), which represent 1/4 of all BBD patients. A training set
      was developed from 86 patients diagnosed with SA, of which 27 subsequently
      developed cancer within 10 years (cases) and 59 remained cancer-free at 10 years
      (controls). An diagonal linear discriminate analysis-prediction model for
      prediction of cancer within 10 years (SA TTC10) was generated from
      transcriptional profiles of FFPE biopsy-derived RNA. This model was tested on a
      separate validation case-control set composed of 65 SA patients. The SA TTC10
      gene signature model, composed of 35 gene features, achieved a clear and
      significant separation between case and control with receiver operating
      characteristic area under the curve of 0.913 in the training set and 0.836 in the
      validation set. Our results provide the first demonstration that benign breast
      tissue contains transcriptional alterations that indicate risk of breast cancer
      development, demonstrating that essential precursor biomarkers of malignancy are
      present many years prior to cancer development. Furthermore, the SA TTC10 gene
      signature model, which can be assessed on FFPE biopsies, constitutes a novel
      prognostic biomarker for patients with SA.

PMID- 26202056
TI  - Imaging of congenital pancreatic lesions: emphasis on key imaging features.
AB  - Congenital pancreatic lesions are relatively uncommon, but they are frequently
      encountered during radiologic examination as an incidental finding in
      asymptomatic patients. However, some of these entities may produce symptoms such
      as abdominal pain, nausea, vomiting and gastric outlet obstruction. This article
      reviews normal pancreatic anatomy, imaging findings of congenital pancreatic
      lesions, including congenital pancreatic anomalies, congenital pancreatic ductal
      variants, pancreatic contour variants, congenital pancreatic cysts, and mimics of
      pancreatic lesions with emphasis on key imaging features. 

PMID- 26202057
TI  - Primary care appointment availability for new Medicaid patients increased after
      Medicaid expansion in Michigan.
AB  - The Affordable Care Act expands health insurance coverage to millions of
      Americans, but the availability of health care services for the newly insured
      population remains uncertain. We conducted a simulated patient (or "secret
      shopper") study to assess primary care appointment availability and wait times
      for new patients with Medicaid or private insurance before and after
      implementation of Michigan's Medicaid expansion in 2014. The expansion, which was
      made possible through a section 1115 waiver, has a unique requirement that new
      beneficiaries must be seen by a primary care provider within 60-90 days of
      enrollment. During a period of rapid coverage expansion in Michigan, we found
      that appointment availability increased 6 percentage points for new Medicaid
      patients and decreased 2 percentage points for new privately insured patients,
      compared to availability before the expansion. Wait times remained stable, at 1-2
      weeks for both groups. Further research is needed to determine whether access to
      primary care for newly insured patients will endure over time. 

PMID- 26202058
TI  - Tool for assessing health and equity impacts of interventions modifying air
      quality in urban environments.
AB  - BACKGROUND: Urban outdoor air pollution (AP) is a major public health concern but
      the mechanisms by which interventions impact health and social inequities are
      rarely assessed. Health and equity impacts of policies and interventions are
      questioned, but managers and policy agents in various institutional contexts have
      very few practical tools to help them better orient interventions in sectors
      other than the health sector. Our objective was to create such a tool to
      facilitate the assessment of health impacts of urban outdoor AP interventions by
      non-public health experts. METHODS: An iterative process of reviewing the
      academic literature, brainstorming, and consultation with experts was used to
      identify the chain of effects of urban outdoor AP and the major modifying
      factors. To test its applicability, the tool was applied to two interventions,
      the London Low Emission Zone and the Montreal BIXI public bicycle-sharing
      program. RESULTS: We identify the chain of effects, six categories of modifying
      factors: those controlling the source of emissions, the quantity of emissions,
      concentrations of emitted pollutants, their spatial distribution, personal
      exposure, and individual vulnerability. Modifiable and non-modifiable factors are
      also identified. Results are presented in the text but also graphically, as we
      wanted it to be a practical tool, from pollution sources to emission, exposure,
      and finally, health effects. CONCLUSION: The tool represents a practical first
      step to assessing AP-related interventions for health and equity impacts.
      Understanding how different factors affect health and equity through air
      pollution can provide insight to city policymakers pursuing Health in All
      Policies.

PMID- 26202059
TI  - Enantioselective synthesis of lepadins A-D from a phenylglycinol-derived
      hydroquinolone lactam.
AB  - The marine alkaloids (-)-lepadins A-C and (+)-lepadin D, belonging to two
      diastereoisomeric series, were synthesized from an (R)-phenylglycinol-derived
      tricyclic lactam via a common cis-decahydroquinoline intermediate. Crucial
      aspects of the synthesis are the stereochemical control in the assembly of the
      cis-decahydroquinoline platform, in the introduction of the C2 methyl and C3
      hydroxy substituents, and in the generation of the C5 stereocenter. 

PMID- 26202060
TI  - Prolactin- and testosterone-induced carboxypeptidase-D correlates with increased
      nitrotyrosines and Ki67 in prostate cancer.
AB  - BACKGROUND: Carboxypeptidase-D (CPD) cleaves C-terminal arginine for conversion
      to nitric oxide (NO) by nitric oxide synthase (NOS). Prolactin (PRL) and
      androgens stimulate CPD gene transcription and expression, which increases
      intracellular production of NO to promote viability of prostate cancer (PCa)
      cells in vitro. The current study evaluated whether hormonal upregulation of CPD
      and NO promote PCa cell viabilty in vivo, by correlating changes in expression of
      CPD and nitrotyrosine residues (products of NO action) with proliferation marker
      Ki67 and associated proteins during PCa development and progression. METHODS:
      Fresh prostate tissues, obtained from 40 men with benign prostatic hyperplasia
      (BPH) or PCa, were flash-frozen at the time of surgery and used for RT-qPCR
      analysis of CPD, androgen receptor (AR), PRL receptor (PRLR), eNOS, and Ki67
      levels. Archival paraffin-embedded tissues from 113 men with BPH or PCa were used
      for immunohistochemical (IHC) analysis of CPD, nitrotyrosines, phospho-Stat5 (for
      activated PRLR), AR, eNOS/iNOS, and Ki67. RESULTS: RT-qPCR and IHC analyses
      showed strong AR and PRLR expression in benign and malignant prostates. CPD mRNA
      levels increased ~threefold in PCa compared to BPH, which corresponded to a
      twofold increase in Ki67 mRNA levels. IHC analysis showed a progressive increase
      in CPD from 11.4 +/- 2.1% in benign to 21.8 +/- 3.2% in low-grade (P = 0.007),
      40.7 +/- 4.0% in high-grade (P < 0.0001) and 50.0 +/- 9.5% in castration
      recurrent PCa (P < 0.0001). Immunostaining for nitrotyrosines and Ki67 mirrored
      these increases during PCa progression. CPD, nitrotyrosines, and Ki67 tended to
      co-localize, as did phospho-Stat5. CONCLUSIONS: CPD, nitrotyrosine, and Ki67
      levels were higher in PCa than in benign and tended to co-localize, along with
      phospho-Stat5. The strong correlation in expression of these proteins in benign
      and malignant prostate tissues, combined with abundant AR and PRLR, supports in
      vitro evidence that the CPD-Arg-NO pathway is involved in the regulation of PCa
      cell proliferation. It further highlights a role for PRL in the development and
      progression of PCa.

PMID- 26202061
TI  - Tannic acid inhibits the Jak2/STAT3 pathway and induces G1/S arrest and
      mitochondrial apoptosis in YD-38 gingival cancer cells.
AB  - Tannic acid (TA), is a potent anti-oxidant, showing anti-proliferative effects on
      numerous cancers. The ability of TA to induce proliferation inhibition on the
      rare tumor, gingival squamous cell carcinoma (GSCC), comprising <10% of all head
      and neck squamous cell carcinomas was studied in the YD-38 cell line. The main
      goal was to modulate the Jak2/STAT3 pathway using TA and to induce cell cycle
      arrest and apoptosis in GSCC. TA treatment induced G1 arrest and apoptosis in YD
      38 cells. Molecular analysis revealed that TA inhibits Jak2/STAT3 pathway by
      preventing their expression as well as phosphorylation. This inhibition of STAT3
      phosphorylation prevented the nuclear translocation and DNA binding capability of
      STAT3. Together with the inhibition of transcriptional regulatory function of
      STAT3, TA inhibited the expression of G1 phase modulators CDK-4, CDK-6, cyclin D1
      and cyclin E. It is also evidenced that TA exerted an intense activation of
      p21Waf1/Cip1, p27Kip1 and p53 genes confirming its role in G1 phase inhibition.
      Additionally, upon treatment with TA, the expression of mitochondrial pore
      factors Bax, Bcl-2 and Bcl-XL were changed. We observed inhibition of Bcl-2 and
      an increase in mitochondrial localization of Bax leading to the loss of
      mitochondrial membrane potential, resulting in the release of cytochrome c to the
      cytosol. In addition, we perceived the activation of caspases upon TA treatment.
      Specific inhibition of caspase protected the cells from TA induced apoptosis.
      Taken together, this study reveals that TA significantly inhibits the Jak2/STAT3
      signaling pathway and induces G1 arrest and mitochondrial apoptosis in YD-38
      cells. 

PMID- 26202062
TI  - Cross-species comparison of relative potencies and relative sensitivities of
      fishes to dibenzo-p-dioxins, dibenzofurans, and polychlorinated biphenyls in
      vitro.
AB  - Dioxin-like compounds of varying toxicities are found in complex mixtures. The
      toxic equivalency factor (TEF) approach was developed based on the potency of a
      dioxin-like compound relative to the potency of 2,3,7,8-tetrachloro-dibenzo-p
      dioxin (TCDD) to streamline risk assessment. One limitation of the TEF approach
      is uncertainty regarding differences in the relative potency of dioxin-like
      compounds among different species. Relative potencies among fishes are limited,
      relative to relative potencies among birds and mammals, and TEFs for fishes are
      based entirely on the model species, rainbow trout (Oncorhynchus mykiss). An in
      vitro liver explant assay was used to characterize species-specific responses
      with regard to up-regulation of CYP1A transcript after exposure to 6 dioxin-like
      compounds in rainbow trout, white sturgeon (Acipenser transmontanus), lake
      sturgeon (Acipenser fulvescens), and northern pike (Esox lucius). Differences in
      sensitivities were observed among species after exposure to dioxin-like
      compounds. The relative potencies developed from liver explants of rainbow trout
      were comparable to relative potencies developed from embryo toxicity assays.
      Differences in relative potencies between species with the least and greatest
      relative potencies were up to 40-fold. To compare relative potencies among
      species, concentrations of dioxin-like compounds in fish eggs in the Fraser River
      and in Lake Ontario were used to calculate toxic equivalency quotients (TEQs)
      determined from TEFs or TCDD equivalents determined from relative potencies. The
      TEQs underestimated TCDD equivalents for white sturgeon, lake sturgeon, and
      northern pike, indicating uncertainty in application of TEFs to diverse fishes.

PMID- 26202063
TI  - Cognitive Impairment and Its Structural Correlates in the Parkinsonian Subtype of
      Multiple System Atrophy.
AB  - BACKGROUND/AIMS: Previous studies indicate that patients with the parkinsonian
      subtype of multiple system atrophy (MSA-P) experience cognitive impairment. This
      study aimed to identify the existence of cognitive impairments and the different
      topographic patterns of morphological changes in MSA-P by means of imaging
      analysis, and also whether these morphological changes could be associated with
      cognitive dysfunctions in MSA-P. METHODS: We recruited 15 nondemented probable
      MSA-P patients and 32 normal controls (NC) for neuropsychological testing and
      MRI. We analyzed morphological changes using cortical thickness analysis, voxel
      based morphometry (VBM) and cerebellar volumetry. Multiple linear regression
      analysis was performed to evaluate the correlation of each cognitive score with
      the mean thickness of significant cortical-thinning clusters, mean gray-matter
      density of VBM clusters and cerebellar volume. RESULTS: The scores on the Digit
      Span Test, the Seoul Verbal Learning Test (immediate and delayed), the phonemic
      Controlled Oral Word Association Test and the Stroop color test were
      significantly lower in the MSA-P group than in the NC group. We found two
      clusters exhibiting significant cortical thinning in the right paracentral lobule
      and parahippocampal gyrus. VBM analysis revealed significant gray-matter atrophy
      in the MSA-P group in the bilateral basal ganglia, cerebellum and temporal and
      frontal cortical areas. Multiple linear regression analysis demonstrated that
      cognitive dysfunction correlated significantly with thinning in the neocortex,
      cerebellum and striatum. CONCLUSIONS: Our data demonstrate that cortical and
      cerebellar atrophy and striatal degeneration are associated with cognitive
      impairment in patients with MSA-P.

PMID- 26202064
TI  - Quality-by-Design II: Application of Quantitative Risk Analysis to the
      Formulation of Ciprofloxacin Tablets.
AB  - Qualitative risk assessment methods are often used as the first step to
      determining design space boundaries; however, quantitative assessments of risk
      with respect to the design space, i.e., calculating the probability of failure
      for a given severity, are needed to fully characterize design space boundaries.
      Quantitative risk assessment methods in design and operational spaces are a
      significant aid to evaluating proposed design space boundaries. The goal of this
      paper is to demonstrate a relatively simple strategy for design space definition
      using a simplified Bayesian Monte Carlo simulation. This paper builds on a
      previous paper that used failure mode and effects analysis (FMEA) qualitative
      risk assessment and Plackett-Burman design of experiments to identity the
      critical quality attributes. The results show that the sequential use of
      qualitative and quantitative risk assessments can focus the design of experiments
      on a reduced set of critical material and process parameters that determine a
      robust design space under conditions of limited laboratory experimentation. This
      approach provides a strategy by which the degree of risk associated with each
      known parameter can be calculated and allocates resources in a manner that
      manages risk to an acceptable level.

PMID- 26202065
TI  - pH-Dependent Solubility and Dissolution Behavior of Carvedilol--Case Example of a
      Weakly Basic BCS Class II Drug.
AB  - The objective of this study was to investigate the pH-dependent solubility and
      dissolution of weakly basic Biopharmaceutical Classification Systems (BCS) class
      II drugs, characterized by low solubility and high permeability, using
      carvedilol, a weak base with a pK a value of 7.8, as a model drug. A series of
      solubility and in vitro dissolution studies was carried out using media that
      simulate the gastric and intestinal fluids and cover the physiological pH range
      of the GI from 1.2 to 7.8. The effect of ionic strength, buffer capacity, and
      buffer species of the dissolution media on the solubility and dissolution
      behavior of carvedilol was also investigated. The study revealed that carvedilol
      exhibited a typical weak base pH-dependent solubility profile with a high
      solubility at low pH (545.1-2591.4 MUg/mL within the pH range 1.2-5.0) and low
      solubility at high pH (5.8-51.9 MUg/mL within the pH range 6.5-7.8). The
      dissolution behavior of carvedilol was consistent with the solubility results,
      where carvedilol release was complete (95.8-98.2% released within 60 min) in
      media simulating the gastric fluid (pH 1.2-5.0) and relatively low (15.9-86.2%
      released within 240 min) in media simulating the intestinal fluid (pH 6.5-7.8).
      It was found that the buffer species of the dissolution media may influence the
      solubility and consequently the percentage of carvedilol released by forming
      carvedilol salts of varying solubilities. Carvedilol solubility and dissolution
      decreased with increasing ionic strength, while lowering the buffer capacity
      resulted in a decrease in carvedilol solubility and dissolution rate.

PMID- 26202066
TI  - Expression and activity of NOD1 and NOD2/RIPK2 signalling in mononuclear cells
      from patients with rheumatoid arthritis.
AB  - OBJECTIVES: The aim of this study was to analyse the expression and function of
      nucleotide-binding oligomerization domain (NOD)1 and NOD2 in isolated cells of
      patients with rheumatoid arthritis (RA). METHOD: mRNA expression levels of NOD1,
      NOD2, and receptor-interacting serine/threonine kinase 2 (RIPK2) genes were
      determined by quantitative polymerase chain reaction (qPCR) in peripheral blood
      mononuclear cells (PBMCs) and synovial fluid T cells (SFTCs) isolated from RA and
      osteoarthritis (OA) patients. Cytokines were measured by enzyme-linked
      immunosorbent assay (ELISA) in plasma and cell culture supernatants. The
      stimulatory effect of RA SF was assessed by an in-vitro NOD2 activation assay
      using nuclear factor kappa B (NF-kappaB) luciferase-transfected cells. RESULTS: A
      significantly higher level of NOD2 and RIPK2 mRNA expression, but not NOD1, was
      observed on PBMCs and SFTCs isolated from RA patients compared to the OA control
      group. In addition, the NOD2 pathway up-regulation was functional, as stimulation
      of PBMCs with muramyl dipeptide (MDP) induced the production of higher amounts of
      tumour necrosis factor (TNF)-alpha, interleukin (IL)-8, and IL-1beta compared
      with OA PBMCs. Incubation of PBMCs from healthy donors with recombinant TNF-alpha
      or RA serum induced the expression of NOD2 mRNA. Finally, SF isolated from RA
      patients is able to activate the NF-kappaB signalling pathway in HEK293T
      transfected cells in a NOD2-dependent manner. CONCLUSIONS: Our findings suggest
      that NOD2/RIPK2 signalling is up-regulated in immune cells of RA patients.
      Moreover, it seems that there is a NOD2 agonist in the SF of RA patients.
      Therefore, NOD2/RIPK2 activation can modulate the innate immune response and may
      play a role in the perpetuation of the inflammatory response in RA.

PMID- 26202068
TI  - A systematic review of hospital accreditation: the challenges of measuring
      complex intervention effects.
AB  - BACKGROUND: The increased international focus on improving patient outcomes,
      safety and quality of care has led stakeholders, policy makers and healthcare
      provider organizations to adopt standardized processes for evaluating healthcare
      organizations. Accreditation and certification have been proposed as
      interventions to support patient safety and high quality healthcare. Guidelines
      recommend accreditation but are cautious about the evidence, judged as
      inconclusive. The push for accreditation continues despite sparse evidence to
      support its efficiency or effectiveness. METHODS: We searched MEDLINE, EMBASE and
      The Cochrane Library using Medical Subject Headings (MeSH) indexes and keyword
      searches in any language. Studies were assessed using the Cochrane Risk of Bias
      Tool and AMSTAR framework. 915 abstracts were screened and 20 papers were
      reviewed in full in January 2013. Inclusion criteria included studies addressing
      the effect of hospital accreditation and certification using systematic reviews,
      randomized controlled trials, observational studies with a control group, or
      interrupted time series. Outcomes included both clinical outcomes and process
      measures. An updated literature search in July 2014 identified no new studies.
      RESULTS: The literature review uncovered three systematic reviews and one
      randomized controlled trial. The lone study assessed the effects of accreditation
      on hospital outcomes and reported inconsistent results. Excluded studies were
      reviewed and their findings summarized. CONCLUSION: Accreditation continues to
      grow internationally but due to scant evidence, no conclusions could be reached
      to support its effectiveness. Our review did not find evidence to support
      accreditation and certification of hospitals being linked to measurable changes
      in quality of care as measured by quality metrics and standards. Most studies did
      not report intervention context, implementation, or cost. This might reflect the
      challenges in assessing complex, heterogeneous interventions such as
      accreditation and certification. It is also may be magnified by the impact of how
      accreditation is managed and executed, and the varied financial and
      organizational healthcare constraints. The strategies hospitals should impelment
      to improve patient safety and organizational outcomes related to accreditation
      and certification components remains unclear.

PMID- 26202067
TI  - The prognostic value of SUMO1/Sentrin specific peptidase 1 (SENP1) in prostate
      cancer is limited to ERG-fusion positive tumors lacking PTEN deletion.
AB  - BACKGROUND: Posttranscriptional protein modification by SUMOylation plays an
      important role in tumor development and progression. In the current study we
      analyzed prevalence and prognostic impact of the de-SUMOylation enzyme SENP1 in
      prostate cancer. METHODS: SENP1 expression was analyzed by immunohistochemistry
      on a tissue microarray containing more than 12,400 prostate cancer specimens.
      Results were compared to tumor phenotype, ERG status, genomic deletions of 3p,
      5q, 6q and PTEN, and biochemical recurrence. RESULTS: SENP1 immunostaining was
      detectable in 34.5 % of 9,516 interpretable cancers and considered strong in 7.3
      %, moderate in 14.9 % and weak in 12.3 % of cases. Strong SENP1 expression was
      linked to advanced pT stage (p < 0.0001), high Gleason grade (p < 0.0001),
      positive lymph node status (p = 0.0019), high pre-operative PSA levels (p =
      0.0037), and PSA recurrence (p < 0.0001). SENP1 expression was strongly
      associated with positive ERG fusion status as determined by both in situ
      hybridization (FISH) and immunohistochemistry as well as with PTEN deletions.
      Detectable SENP1 immunostaining was found in 41 % of ERG positive and in 47 % of
      PTEN deleted cancers but in only 30 % of ERG negative and 30 % of PTEN non
      deleted cancers (p < 0.0001 each). Deletions of 3p, 5q, and 6q were unrelated to
      SENP1 expression. Subset analyses revealed that the prognostic impact of SENP1
      expression was solely driven by the subgroup of ERG positive, PTEN undeleted
      cancers. In this subgroup, the prognostic role of SENP1 expression was
      independent of the preoperative PSA level, tumor stage, Gleason grade, and the
      status of the resection margin. CONCLUSIONS: SENP1 expression has strong
      prognostic impact in a molecularly defined subset of cancers. This is per se not
      surprising as the biologic impact of each individual molecular event is likely to
      be dependent on its cellular environment. However, such findings challenge the
      concept of finding clinically relevant molecular signatures that are equally
      applicable to all prostate cancers.

PMID- 26202069
TI  - A recombinant Sal k 1 isoform as an alternative to the polymorphic allergen from
      Salsola kali pollen for allergy diagnosis.
AB  - BACKGROUND: The incidence of Amaranthaceae pollen allergy has increased due to
      the desertification occurring in many countries. In some regions of Spain,
      Salsola kali is the main cause of pollinosis, at almost the same level as olive
      and grass pollen. Sal k 1 - the sensitization marker of S. kali pollinosis - is
      used in clinical diagnosis, but is purified at a low yield from pollen. We aimed
      to produce a recombinant (r)Sal k 1 able to span the structural and immunological
      properties of the natural isoforms from pollen, and validate its potential use
      for diagnosis. METHODS: Specific cDNA was amplified by PCR, cloned into the
      pET41b vector and used to transform BL21 (DE3) Escherichia coli cells.
      Immunoblotting, ELISA, basophil activation and skin-prick tests were used to
      validate the recombinant protein against Sal k 1 isolated from pollen. Sera and
      blood cells from S. kali pollen-sensitized patients and specific monoclonal and
      polyclonal antisera were used. RESULTS: rSal k 1 was produced in bacteria with a
      yield of 7.5 mg/l of cell culture. The protein was purified to homogeneity and
      structural and immunologically validated against the natural form. rSal k 1
      exhibited a higher IgE cross-reactivity with plant-derived food extracts such as
      peanut, almond or tomato than with pollen sources such as Platanus acerifolia and
      Oleaceae members. CONCLUSIONS: rSal k 1 expressed in bacteria retains intact
      structural and immunological properties in comparison to the pollen-derived
      allergen. It spans the immunological properties of most of the isoforms found in
      pollen, and it might substitute natural Sal k 1 in clinical diagnosis.

PMID- 26202070
TI  - Transgenic expression of the human growth hormone minigene promotes pancreatic
      beta-cell proliferation.
AB  - Transgenic mouse models are designed to study the role of specific proteins. To
      increase transgene expression the human growth hormone (hGH) minigene, including
      introns, has been included in many transgenic constructs. Until recently, it was
      thought that the hGH gene was not spliced, transcribed, and translated to produce
      functional hGH protein. We generated a transgenic mouse with the transcription
      factor Forkhead box M1 (FoxM1) followed by the hGH minigene, under control of the
      mouse insulin promoter (MIP) to target expression specifically in the pancreatic
      beta-cell. Expression of FoxM1 in isolated pancreatic islets in vitro stimulates
      beta-cell proliferation. We aimed to investigate the effect of FoxM1 on beta-cell
      mass in a mouse model for diabetes mellitus. However, we found inadvertent
      coexpression of hGH protein from a spliced, bicistronic mRNA. MIP-FoxM1-hGH mice
      had lower blood glucose and higher pancreatic insulin content, due to increased
      beta-cell proliferation. hGH signals through the murine prolactin receptor, and
      expression of its downstream targets tryptophan hydroxylase-1 (Tph1), tryptophan
      hydroxylase-2 (Tph2), and cytokine-inducible SH2 containing protein (Cish) was
      increased. Conversely, transcriptional targets of FoxM1 were not upregulated. Our
      data suggest that the phenotype of MIP-FoxM1-hGH mice is due primarily to hGH
      activity and that the FoxM1 protein remains largely inactive. Over the past
      decades, multiple transgenic mouse strains were generated that make use of the
      hGH minigene to increase transgene expression. Our work suggests that each will
      need to be carefully screened for inadvertent hGH production and critically
      evaluated for the use of proper controls. 

PMID- 26202072
TI  - Negative Cognitive Errors in Youth: Specificity to Anxious and Depressive
      Symptoms and Age Differences.
AB  - BACKGROUND: Negative cognitive errors are important in the etiology and treatment
      of youth internalizing problems, but less is known about their unique relations
      with anxiety and depression. AIMS: The major purpose of this study was to examine
      associations between distinct negative cognitive errors and anxiety and
      depression in youth. METHOD: In a community sample of children and adolescents
      (aged 9-17; N = 278) negative cognitive errors were assessed using the revised
      version of the Children's Negative Cognitive Error Questionnaire (CNCEQ-R).
      Anxiety and depression were assessed with the Multidimensional Anxiety Scale for
      Children and Children's Depression Inventory, respectively. RESULTS: The
      strongest predictors of anxiety were the negative cognitive errors
      "underestimation of the ability to cope" and "mind reading". The strongest
      predictors of depression were the errors "selective abstraction" and
      "overgeneralizing", with the first error explaining most variance. Analyses of
      age effects showed that, in comparison to adolescents, children reported higher
      scores on the total CNCEQ-R score, and on the errors "overgeneralizing",
      "personalizing", and "mind reading". CONCLUSIONS: The findings underscore the
      importance of researching the role of distinct cognitive processing in youth with
      anxiety and depression and further development of the CNCEQ-R. Implications for
      clinical practice are discussed.

PMID- 26202073
TI  - Do Females with Bulimia Nervosa and Eating Disorder Not Otherwise Specified Have
      Selective Memory Biases?
AB  - BACKGROUND: The cognitive model suggests memory biases for weight/shape and food
      related information could be important in the maintenance of eating disorders.
      AIMS: The current study aims to evaluate this and extend previous research by (a)
      including females with eating disorder not otherwise specified (EDNOS) as a
      discreet group; (b) considering whether levels of hunger and the pleasantness of
      the stimulus words are important in word recall. METHOD: The study includes three
      groups of females, 16 with bulimia nervosa, 18 with EDNOS and 17 non-dieting
      general population controls. All participants completed a self-referential
      encoding and memory recall task. RESULTS: A main effect of word type (p < .01)
      with no group by word type interaction or between group difference was found. A
      priori contrasts indicated that both eating disorder groups recalled
      significantly more weight/shape and food words compared to all other word
      categories (p < .01) compared to the control group; with no significant
      difference found between the eating disorder groups. In relation to the recall of
      food words, no significant differences were found between groups for levels of
      hunger. Both eating disorder groups rated the negative weight/shape (p < .01),
      negative food (p < .01) and neutral body words (p < .01) as more unpleasant than
      the control group. CONCLUSIONS: The implications for cognitive theory and future
      research are discussed.

PMID- 26202071
TI  - Blood flow-restricted strength training displays high functional and biological
      efficacy in women: a within-subject comparison with high-load strength training.
AB  - Limited data exist on the efficacy of low-load blood flow-restricted strength
      training (BFR), as compared directly to heavy-load strength training (HST). Here,
      we show that 12 wk of twice-a-week unilateral BFR [30% of one repetition maximum
      (1RM) to exhaustion] and HST (6-10RM) of knee extensors provide similar increases
      in 1RM knee extension and cross-sectional area of distal parts of musculus
      quadriceps femoris in nine untrained women (age 22 +/- 1 yr). The two protocols
      resulted in similar acute increases in serum levels of human growth hormone. On
      the cellular level, 12 wk of BFR and HST resulted in similar shifts in muscle
      fiber composition in musculus vastus lateralis, evident as increased MyHC2A
      proportions and decreased MyHC2X proportions. They also resulted in similar
      changes of the expression of 29 genes involved in skeletal muscle function,
      measured both in a rested state following 12 wk of training and subsequent to
      singular training sessions. Training had no effect on myonuclei proportions. Of
      particular interest, 1) gross adaptations to BFR and HST were greater in
      individuals with higher proportions of type 2 fibers, 2) both BFR and HST
      resulted in approximately four-fold increases in the expression of the novel
      exercise-responsive gene Syndecan-4, and 3) BFR provided lesser hypertrophy than
      HST in the proximal half of musculus quadriceps femoris and also in CSApeak,
      potentially being a consequence of pressure from the tourniquet utilized to
      achieve blood flow restriction. In conclusion, BFR and HST of knee extensors
      resulted in similar adaptations in functional, physiological, and cell biological
      parameters in untrained women. 

PMID- 26202074
TI  - Profiling Metacognition in Gambling Disorder.
AB  - BACKGROUND: Preliminary research has indicated that general facets of
      metacognition are associated with problem gambling. In the present study we aimed
      to investigate whether specific facets of metacognition play a role in explaining
      gambling initiation and perseveration in individuals presenting with gambling
      disorder. AIM: To investigate: (1) the presence of metacognitive beliefs about
      gambling; (2) the goal of gambling, and its start and stop signals; and (3) the
      perceived impact of gambling on self-consciousness. METHOD: Ten individuals with
      a diagnosis of gambling disorder were assessed using metacognitive profiling, a
      semi-structured interview. RESULTS: Findings indicated that all participants
      endorsed both positive and negative metacognitive beliefs about gambling. The
      primary goal of gambling was to relieve economic hardship and improve cognitive
      emotional state. All participants reported that they did not know when this goal
      was achieved. Start signals for gambling included the ideas and feelings that
      gambling could solve problems and sensations that it might be the right time to
      win. The stop signal for gambling, for all participants, was running out of
      money. All participants also reported a perceived reduction in self-consciousness
      during a gambling episode. CONCLUSIONS: These findings provide preliminary
      evidence that specific facets of metacognition play a role in gambling disorder.

PMID- 26202076
TI  - Community-acquired diarrhoea in a world with rotavirus vaccine: a glimpse into
      the future.

PMID- 26202075
TI  - Pathogen-specific burdens of community diarrhoea in developing countries: a
      multisite birth cohort study (MAL-ED).
AB  - BACKGROUND: Most studies of the causes of diarrhoea in low-income and middle
      income countries have looked at severe disease in people presenting for care, and
      there are few estimates of pathogen-specific diarrhoea burdens in the community.
      METHODS: We undertook a birth cohort study with not only intensive community
      surveillance for diarrhoea but also routine collection of non-diarrhoeal stools
      from eight sites in South America, Africa, and Asia. We enrolled children within
      17 days of birth, and diarrhoeal episodes (defined as maternal report of three or
      more loose stools in 24 h, or one loose stool with visible blood) were identified
      through twice-weekly home visits by fieldworkers over a follow-up period of 24
      months. Non-diarrhoeal stool specimens were also collected for surveillance for
      months 1-12, 15, 18, 21, and 24. Stools were analysed for a broad range of
      enteropathogens using culture, enzyme immunoassay, and PCR. We used the adjusted
      attributable fraction (AF) to estimate pathogen-specific burdens of diarrhoea.
      FINDINGS: Between November 26, 2009, and February 25, 2014, we tested 7318
      diarrhoeal and 24 310 non-diarrhoeal stools collected from 2145 children aged 0
      24 months. Pathogen detection was common in non-diarrhoeal stools but was higher
      with diarrhoea. Norovirus GII (AF 5.2%, 95% CI 3.0-7.1), rotavirus (4.8%, 4.5
      5.0), Campylobacter spp (3.5%, 0.4-6.3), astrovirus (2.7%, 2.2-3.1), and
      Cryptosporidium spp (2.0%, 1.3-2.6) exhibited the highest attributable burdens of
      diarrhoea in the first year of life. The major pathogens associated with
      diarrhoea in the second year of life were Campylobacter spp (7.9%, 3.1-12.1),
      norovirus GII (5.4%, 2.1-7.8), rotavirus (4.9%, 4.4-5.2), astrovirus (4.2%, 3.5
      4.7), and Shigella spp (4.0%, 3.6-4.3). Rotavirus had the highest AF for sites
      without rotavirus vaccination and the fifth highest AF for sites with the
      vaccination. There was substantial variation in pathogens according to geography,
      diarrhoea severity, and season. Bloody diarrhoea was primarily associated with
      Campylobacter spp and Shigella spp, fever and vomiting with rotavirus, and
      vomiting with norovirus GII. INTERPRETATION: There was substantial heterogeneity
      in pathogen-specific burdens of diarrhoea, with important determinants including
      age, geography, season, rotavirus vaccine usage, and symptoms. These findings
      suggest that although single-pathogen strategies have an important role in the
      reduction of the burden of severe diarrhoeal disease, the effect of such
      interventions on total diarrhoeal incidence at the community level might be
      limited.

PMID- 26202077
TI  - Threonine affects digestion capacity and hepatopancreatic gene expression of
      juvenile blunt snout bream (Megalobrama amblycephala).
AB  - The present study conducted a 9-week feeding trial to investigate the effects of
      threonine (Thr) on the digestion capacity and hepatopancreas gene expression of
      juvenile blunt snout bream (Megalobrama amblycephala). For this purpose, three
      tanks (300 litres/tank) were randomly arranged and assigned to each experimental
      diet. Juvenile fish were fed with diets containing graded Thr levels (0.58, 1.08,
      1.58, 2.08 or 2.58 % of the diet) to apparent satiation four times daily. At the
      end of the feeding trial, the results indicated that hepatopancreas weight,
      hepatosomatic index, hepatopancreatic protein content, intestinal weight,
      intestosomatic index and intestinal protein content increased with increasing
      dietary Thr levels up to 1.58 % and thereafter decreased (P< 0.05). The
      activities of chymotrypsin, trypsin, amylase and lipase elevated as dietary Thr
      levels increased up to 1.58 % (P< 0.05), while these activities decreased in most
      cases after 1.58 % dietary Thr except for chymotrypsin and trypsin in the
      hepatopancreas (plateau 1.58-2.08 % Thr). The relative gene expression levels of
      chymotrypsin, trypsin, amylase, lipase, target of rapamycin and insulin-like
      growth factor-I were up-regulated, and the highest values were observed with 1.58
      % dietary Thr or 1.58 and 2.08 % dietary Thr, whereas the relative gene
      expression levels of eukaryotic translation initiation factor 4E-binding protein
      2 gradually decreased (P< 0.10) as dietary Thr levels increased up to 1.58 % and
      thereafter significantly increased (P< 0.05), which could explain that about 1.58
      % dietary Thr could improve the growth and development of digestive organs and
      activities of digestive enzymes of juvenile blunt snout bream.

PMID- 26202078
TI  - Measurement of lentiviral vector titre and copy number by cross-species duplex
      quantitative PCR.
AB  - Lentiviruses are the vectors of choice for many preclinical studies and clinical
      applications of gene therapy. Accurate measurement of biological vector titre
      before treatment is a prerequisite for vector dosing, and the calculation of
      vector integration sites per cell after treatment is as critical to the
      characterisation of modified cell products as it is to long-term follow-up and
      the assessment of risk and therapeutic efficiency in patients. These analyses are
      typically based on quantitative real-time PCR (qPCR), but as yet compromise
      accuracy and comparability between laboratories and experimental systems, the
      former by using separate simplex reactions for the detection of endogene and
      lentiviral sequences and the latter by designing different PCR assays for
      analyses in human cells and animal disease models. In this study, we validate in
      human and murine cells a qPCR system for the single-tube assessment of lentiviral
      vector copy numbers that is suitable for analyses in at least 33 different
      mammalian species, including human and other primates, mouse, pig, cat and
      domestic ruminants. The established assay combines the accuracy of single-tube
      quantitation by duplex qPCR with the convenience of one-off assay optimisation
      for cross-species analyses and with the direct comparability of lentiviral
      transduction efficiencies in different species. 

PMID- 26202079
TI  - Thoracic kidney on right side.

PMID- 26202080
TI  - Reception of odors and repellents in mosquitoes.
AB  - Mosquitoes use their sense of smell to find hosts, nectar, and oviposition sites,
      and to avoid repellents. A small number of mosquito species are adapted to feed
      on humans and have a major impact on public health by transmitting diseases such
      as malaria, dengue and filariasis. The application of odorants for behavioral
      control has not been fully realized yet due to complexity of the mosquito
      olfactory system. Recent progress in molecular and computational tools has
      enabled rigorous investigations of the mosquito olfactory system function and has
      started to reveal how specific receptors contribute to attractive and aversive
      behaviors. Here we discuss recent advances in linking odors to receptors and in
      exploiting this knowledge in finding attractants and repellents for mosquitoes. 

PMID- 26202082
TI  - Disentanglement of Discordant Monochorionic-Monoamniotic Twins in a Triplet
      Pregnancy: An Innovative Approach Utilizing Fetoscopic Laser Coagulation with
      Micro-Laparoscopic Scissor Dissection.
AB  - Triplet gestations are associated with high perinatal morbidity. Dichorionic
      diamniotic triplet pregnancies with growth discordance, polyhydramnios and
      structural anomalies carry a significantly increased risk of fetal morbidity and
      mortality from the baseline risks of high-order multiple pregnancies.
      Intrauterine fetal death of one fetus of a monochorionic pregnancy may cause
      neurological injury to the surviving fetus. We present a case where an innovative
      technique was created combining use of the fetoscopic laser and miniature
      laparoscopic instruments to selectively reduce and disentangle the umbilical cord
      of the acranial growth-restricted fetus from the structurally normal fetus's
      umbilical cord in a dichorionic-diamniotic triplet pregnancy.

PMID- 26202081
TI  - Comparison of the heart failure risk stratification performance of the CKD-EPI
      equation and the MDRD equation for estimated glomerular filtration rate in
      patients with Type 2 diabetes.
AB  - AIMS: To investigate the risk prediction and the risk stratification performances
      of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and
      the Modification of Diet in Renal Disease (MDRD) equation for estimated
      glomerular filtration rate (eGFRCKD - EPI vs. eGFRMDRD ) on heart failure in
      patients with Type 2 diabetes. METHODS: The study cohort included 12 258 White
      and 16 886 African American low-income patients with Type 2 diabetes who were 30
      90 years old at baseline. Heart failure risk according to different eGFRCKD - EPI
      and eGFRMDRD categories was prospectively assessed. RESULTS: During a mean follow
      up of 6.5 years, 5043 incident heart failure cases were identified. Multivariable
      adjusted hazard ratios (HRs) of heart failure associated with the eGFRCKD - EPI
      categories [>= 90 (reference group), 75-89, 60-74, 30-59 and < 30 ml/min/1.73
      m(2) ] were 1.00, 1.11, 1.31, 1.75 and 2.93 (Ptrend < 0.001) for African American
      patients, and 1.00, 1.11, 1.08, 1.59 and 2.92 (Ptrend < 0.001) for White
      patients, respectively. The model with eGFRCKD - EPI and the other risk factors
      had significantly higher Harrell's C than the model with eGFRMDRD and other risk
      factors. Patients reclassified downward from eGFRMDRD 60-74 to eGFRCKD - EPI 30
      59 and from eGFRMDRD 30-59 to eGFRCKD - EPI < 30 ml/min/1.73 m(2) showed higher
      heart failure risk than those who were not reclassified. CONCLUSIONS: Impaired
      kidney function (i.e. GFR < 60 ml/min/1.73 m(2) ), and even mildly decreased GFR
      (60-74 ml/min/1.73 m(2) ) estimated by both equations is associated with an
      increased risk of heart failure. Compared with GFR estimated using the MDRD
      equation, GFR estimated using the CKD-EPI equation added more predictive power to
      the model with the other risk factors. Also, eGFRCKD - EPI provided more accurate
      heart failure risk stratification than eGFRMDRD .

PMID- 26202083
TI  - Bcl10 crucially nucleates the pro-apoptotic complexes comprising PDK1, PKCzeta
      and caspase-3 at the nuclear envelope of etoposide-treated human cervical
      carcinoma C4-I cells.
AB  - Protein kinase (PK)Czeta signaling at various subcellular levels affects cell
      survival, differentiation, growth and/or apoptosis. However, the mechanisms
      modulating PKCzeta activity at the nuclear membrane (NM) are not yet fully
      understood. Previously, we demonstrated that PKCzeta interacts with the B-cell
      lymphoma 10 (Bcl10) protein at the NM of human cervical carcinoma (HCC) C4-I
      cells. In the present study, we aimed to further clarify the interactions between
      PKCzeta, Bcl10 and other proteins co-immunoprecipitated from NMs isolated from
      untreated and etoposide (also known as VP-16; 2.0 ug/ml)-treated C4-I cells using
      biochemical and proteomics analyses. Aside from the Bcl10 protein, 3
      phosphoinositide-dependent protein kinase-1 (PDK1) also co-immunoprecipitated
      with PKCzeta from NMs of C4-I cells, indicating the assembly of a heterotrimeric
      complex, which increased with time in VP-16-exposed cells, as did the activity of
      PDK1-phosphorylated-PKCzeta. In turn, PKCzeta-phosphorylated-Bcl10 straddled an
      enlarged complex which comprised caspase-3. Subsequently, activity-enhanced
      caspase-3 cleaved and inactivated PKCzeta. Finally, the suppression of Bcl10
      using specific siRNA or lentiviral transduction prevented the increase in the
      PDK1*PKCzeta association, the increase in the activity of PKCzeta and caspase-3,
      as well as the caspase-3-mediated PKCzeta proteolysis and inactivation from
      occurring at the NMs of the VP-16-exposed C4-I cells. Our observations provide
      evidence that Bcl10 acts as a pivotal pro-apoptotic protein which crucially
      nucleates complexes comprising PDK1, PKCzeta and active caspase-3 at the NMs of
      VP-16-exposed C4-I cells. Hence, our data suggest that Bcl10 and PKCzeta are
      potential therapeutic targets in the treatment of HCC.

PMID- 26202084
TI  - MiR-135a Suppresses Calcification in Senescent VSMCs by Regulating KLF4/STAT3
      Pathway.
AB  - Cellular function phenotype is regulated by various microRNAs (miRs), including
      miR-135a. However, how miR-135a is involved in the calcification in senescent
      vascular smooth muscle cells (VSMCs) is not clear yet. In the present study, we
      first identified the significantly altered miRNAs in VSMCs, then performed
      consecutive passage culture of VSMCs and analyzed the expression of miR- 135a and
      calcification genes in the senescent phase. Next, the effects of the miR-135a
      inhibition on calcification and calcification genes were analyzed. The luciferase
      assay was used to validate the target protein of miR-135a. The western blotting
      was used to determine the effects of miR-135a on Kruppel-like factor 4 (KLF4) and
      signal transducer and activator of transcription 3 protein (STAT3) expression, as
      well as the relationship between KLF4 and STAT3. Finally, the quantified cellular
      calcification was measured to examine the involvement of miR-135a, KLF4 and STAT3
      in VSMCs calcification. Our results showed that miR-135a was significantly
      altered in VSMCs. Cell calcification and calcification genes were greatly altered
      by miR-135a inhibition. KLF4 was validated as the target RNA of miR-135a.
      Expression of KLF4 and STAT3 were both significantly decreased by over expressed
      miR-135a, while the inhibition of miR-135a and KLF4 siRNA both decreased the
      STAT3 protein levels. Moreover, the inhibition of miR-135a dramatically increased
      the calcium concentration, but co-treatment with KLF4 or STAT3 siRNA both
      decreased the calcium concentration. The present study identified miR-135a as a
      potential osteogenic differentiation suppressor in senescent VSMCs and revealed
      that KLF4/STAT3 pathway, at least partially, was involved in the mechanism.

PMID- 26202085
TI  - Transtenotic coronary flow velocity assessment: a new road map for non-invasive
      coronary evaluation?

PMID- 26202086
TI  - Tissue Doppler echocardiography predicts acute myocardial infarction, heart
      failure, and cardiovascular death in the general population.
AB  - AIMS: To improve risk prediction of cardiovascular morbidity and mortality, we
      need sensitive markers of cardiac dysfunction; Echocardiographic Tissue Doppler
      Imaging (TDI) is feasible and harmless and may be ideal for this purpose. METHODS
      AND RESULTS: Within the community-based Copenhagen City Heart Study, 2064
      participants were examined by echocardiography including TDI and followed (median
      10.9 years) with regard to cardiovascular death, heart failure, or acute
      myocardial infarction (n = 277). Impaired systolic (s') and diastolic (e' and a')
      function according to age and sex as assessed by TDI was associated with
      increased risk of the combined end point, even in the subgroup of persons with a
      normal conventional echocardiographic examination [per 1 cm/s decrease: s': HR
      1.32 (1.12-1.57), P < 0.001; e': HR 1.17(1.04-1.31), P < 0.01; a': HR 1.17 (1.06
      1.30), P < 0.005]. Interestingly, reduced early diastolic myocardial velocity
      (e') was associated with risk of acute myocardial infarction, whereas reduced
      systolic (s') or late diastolic function (a') was associated with heart failure
      and cardiovascular death independently of traditional risk factors, plasma
      proBNP, and conventional echocardiographic measures. Combining information on
      early and late diastolic function by TDI provided incremental prognostic
      information and improved risk classification (net reclassification improvement:
      27%; P < 0.001) and remained a significant predictor of the combined end point
      even in the subgroup with a normal conventional echocardiographic examination
      [per cm/s decrease: HR 1.18 (1.08-1.28), P < 0.001]. CONCLUSION: In the general
      population, TDI identifies individuals with cardiac dysfunction and high risk of
      cardiovascular morbidity and mortality independently of traditional risk factors,
      even in persons with a normal conventional echocardiographic examination.

PMID- 26202087
TI  - Club 35 EACVI web spotlight: comments on right ventricle assessment in the new
      echocardiography recommendations.

PMID- 26202088
TI  - Transnational multistakeholder partnerships for sustainable development:
      Conditions for success.
AB  - This perspective discusses nine conditions for enhancing the performance of
      multistakeholder partnerships for sustainable development. Such partnerships have
      become mainstream implementation mechanisms for attaining international
      sustainable development goals and are also frequently used in other adjacent
      policy domains such as climate change, health and biodiversity. While
      multistakeholder arrangements are widely perceived as a positive contribution to
      addressing global change, few studies have systematically evaluated the existing
      evidence for their positive performance. This poses an urgent and important
      challenge for researchers and practitioners to understand and improve the
      effectiveness of partnerships, in particular since their popularity increases
      despite their past track record. The recommendations presented are based on own
      research, a literature survey and discussions with a large number or
      international Civil Society Organizations at two occasions during 2014. This
      article proceeds as follows: first, we define multistakeholder partnerships,
      outline their rational and summarize available assessments on partnership
      success; second, we provide a set of concrete recommendations based on lessons
      learned from over 10 years of scholarship; and third, we conclude with some
      reflections on the future of multistakeholder governance for sustainability. 

PMID- 26202089
TI  - Cropland changes in times of conflict, reconstruction, and economic development
      in Iraqi Kurdistan.
AB  - The destruction of land and forced migration during the Anfal attacks against the
      Kurds in Iraq in the late 1980s has been reported to have severe consequences for
      agricultural development. A reconstruction program to aid people in returning to
      their lands was launched in 1991. To assess the agricultural situation in the
      Duhok governorate during the pre-Anfal (A), post-Anfal (B), reconstruction (C),
      and present (D) periods, we mapped winter crops by focusing on inter-annual
      variability in vegetation greenness, using satellite images. The results indicate
      a decrease in cultivated area between period A and B, and a small increase
      between period B and C. This supports reports of a decline in cultivated area
      related to the Anfal campaign, and indicates increased activity during the
      reconstruction program. Period D showed a potential recovery with a cropland area
      similar to period A. 

PMID- 26202090
TI  - Compaction of rolling circle amplification products increases signal integrity
      and signal-to-noise ratio.
AB  - Rolling circle amplification (RCA) for generation of distinct fluorescent signals
      in situ relies upon the self-collapsing properties of single-stranded DNA in
      commonly used RCA-based methods. By introducing a cross-hybridizing DNA
      oligonucleotide during rolling circle amplification, we demonstrate that the
      fluorophore-labeled RCA products (RCPs) become smaller. The reduced size of RCPs
      increases the local concentration of fluorophores and as a result, the signal
      intensity increases together with the signal-to-noise ratio. Furthermore, we have
      found that RCPs sometimes tend to disintegrate and may be recorded as several
      RCPs, a trait that is prevented with our cross-hybridizing DNA oligonucleotide.
      These effects generated by compaction of RCPs improve accuracy of visual as well
      as automated in situ analysis for RCA based methods, such as proximity ligation
      assays (PLA) and padlock probes. 

PMID- 26202091
TI  - Medication reconciliation at admission and discharge: an analysis of prevalence
      and associated risk factors.
AB  - INTRODUCTION: Medication errors are frequent at care transition points and can
      have serious repercussions. Study objectives were to examine the frequency/type
      of reconciliation errors at hospital admission and discharge and to report on the
      drugs involved, associated risk factors and potential to cause harm in a
      healthcare setting with comprehensive digital health records. MATERIAL AND
      METHODS: A prospective observational 2-year study was conducted in the Internal
      Medicine Department of a regional hospital. The best possible medication history
      was obtained from different sources by clinical pharmacists and compared with
      prescriptions at admission and discharge. The frequency and type of
      reconciliation errors were studied at admission and discharge, evaluating risk
      factors for their occurrence and their potential to cause harm. RESULTS: The
      study included 814 patients (mean age: 80.2 years). At least one reconciliation
      error was detected in 525 (64.5%) patients at admission, with a mean of 2.2 +/-
      1.3 errors per patient and in 235 (32.4%) patients at discharge. Drug omission
      was the most frequent reconciliation error (73.6% at admission and 71.4% at
      discharge); 39% of errors at admission and 51% at discharge had potential to
      cause moderate or severe harm. The risk of error at admission was higher with
      more pre-admission drugs (p < 0.001) and, among patients with reconciliation
      errors, the number of errors was significantly higher in those receiving more
      drugs pre-admission or with more comorbidities. The risk at discharge was higher
      in patients with more drugs prescribed at discharge (p = 0.04) and in those with
      a longer hospital stay (p = 0.03). CONCLUSIONS: Medication reconciliation
      procedures are required to minimise medication discrepancies and enhance patient
      safety. Integration of patient health records across care levels is necessary but
      not sufficient to prevent errors.

PMID- 26202092
TI  - Urolithins, gut microbiota-derived metabolites of ellagitannins, inhibit LPS
      induced inflammation in RAW 264.7 murine macrophages.
AB  - SCOPE: Ellagitannin-rich food products and medicinal plant materials were shown
      to have beneficial effects toward intestinal inflammation. Due to the
      questionable bioavailability of ellagitannins their gut microbiota metabolites
      urolithins have come to be regarded as potential factors responsible for
      biological activities observed in vivo. The aim of the study was to determine the
      influence of the three most abundant bioavailable ellagitannin gut microbiota
      metabolites-urolithins A, B, and C on inflammatory responses in RAW 264.7 murine
      macrophages, which are involved in the pathogenesis of intestine inflammation.
      METHODS AND RESULTS: Urolithins A, B, and C decreased NO production via
      inhibition of the iNOS protein and mRNA expression. They decreased the expression
      of IL-1beta, TNF-alpha, and IL-6 mRNA in LPS challenged RAW 264.7 murine
      macrophages. A clear inhibition of NF-kappaB p65 nuclear translocation and p50
      DNA-binding activity was associated with the observed anti-inflammatory
      activities of urolithins. Among the tested compounds urolithin A had the
      strongest anti-inflammatory activity. CONCLUSION: The anti-inflammatory effects
      of urolithins at concentrations that are physiologically relevant for gut tissues
      (>=40 MUM), as revealed in this study, support the data from in vivo studies
      showing the beneficial effects of ellagitannin-rich products toward intestinal
      inflammation.

PMID- 26202093
TI  - Feeding and oral processing behaviors of two colobine monkeys in Tai Forest,
      Ivory Coast.
AB  - We collected frequency data on oral processing behaviors during feeding in
      habituated groups of Western red colobus, Piliocolobus badius, and Western black
      and white, Colobus polykomos, ranging in the Ivory Coast's Tai National Park.
      During the sampling period, the diet of red colobus consisted of approximately
      75% leaves compared to approximately 47% leaves and buds in black and white
      colobus. Black and white colobus chewed more frequently per ingestive event than
      did red colobus. Black and white colobus also employed their anterior teeth much
      more frequently than did red colobus, a difference attributed to the frequent
      consumption by C. polykomos of Pentaclethra macrophylla seeds and pods. A
      material analysis of these food items reveals that both the seed coating and seed
      flesh are quite soft; however, the pod housing the seeds is very tough. We argue
      that the pod's toughness, geometry, and fiber orientation collectively result in
      a food that is very difficult to process, resulting in long handling times and
      frequent, aggressive use of the incisors. We compare these data with those
      collected on another Tai primate-the sooty mangabey, Cercocebus atys-and
      demonstrate that during feeding, both colobine species use their incisors less
      than the mangabey, but that the cercopithecine chews less than either colobine.
      Combining data on oral processing behaviors with those on the material properties
      of items being ingested should lead to more informed interpretations of
      dentognathic morphology.

PMID- 26202094
TI  - Catalytic Silylations of Alcohols: Turning Simple Protecting-Group Strategies
      into Powerful Enantioselective Synthetic Methods.
AB  - In recent years, remarkable progress has been made in the enantioselective
      silylation of alcohols. Owing to the successful site- and stereoselective
      functionalization of hydroxy groups, silyl ether formations have evolved from
      being a simple reaction for functional-group protection into a powerful
      enantioselective process. In this Minireview, we highlight important recent
      findings in this emerging field. 

PMID- 26202095
TI  - The Effect of Silibinin on the Pharmacokinetics of Ivabradine and N
      Desmethylivabradine in Rats.
AB  - The objective of this work was to investigate the effect of orally administered
      silibinin on the pharmacokinetics of ivabradine and its active metabolite N
      desmethylivabradine in rats. Twelve healthy male Sprague-Dawley rats were
      randomly divided into 2 groups: the control group (received oral 1.0 mg/kg
      ivabradine alone) and the combination group (1.0 mg/kg ivabradine orally
      coadministered with 30 mg/kg silibinin). The plasma concentration of ivabradine
      and N-desmethylivabradine were estimated by ultra-performance liquid
      chromatography tandem mass spectrometry (UPLC-MS/MS) and different
      pharmacokinetic parameters were calculated using the DAS 2.0 software. The
      pharmacokinetic parameters of t1/2, Cmax, AUC(0-t) and AUC(0-infinity) of
      ivabradine in the combination group were significantly higher than those in the
      control group (p < 0.01). However, silibinin has no effect on the
      pharmacokinetics of N-desmethylivabradine. This study demonstrates that silibinin
      increase plasma concentration of ivabradine. Henceforth, the pharmacodynamic
      influence of this interaction should be taken into consideration while
      prescribing ivabradine to patients already taking silibinin. 

PMID- 26202096
TI  - The molecular mechanism and physiological role of cytoplasmic streaming.
AB  - Cytoplasmic streaming occurs widely in plants ranging from algae to angiosperms.
      However, the molecular mechanism and physiological role of cytoplasmic streaming
      have long remained unelucidated. Recent molecular genetic approaches have
      identified specific myosin members (XI-2 and XI-K as major and XI-1, XI-B, and XI
      I as minor motive forces) for the generation of cytoplasmic streaming among 13
      myosin XIs in Arabidopsis thaliana. Simultaneous knockout of these myosin XI
      members led to a reduced velocity of cytoplasmic streaming and marked defects of
      plant development. Furthermore, the artificial modifications of myosin XI-2
      velocity changed plant and cell sizes along with the velocity of cytoplasmic
      streaming. Therefore, we assume that cytoplasmic streaming is one of the key
      regulators in determining plant size. 

PMID- 26202098
TI  - Nonalcoholic Steatohepatitis Score is an Independent Predictor of Right
      Ventricular Dysfunction in Patients with Nonalcoholic Fatty Liver Disease.
AB  - OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is associated with increased
      risk of cardiovascular disease and impaired left ventricular (LV) function, yet
      the impact of NAFLD on right ventricular (RV) function remains unclear. We
      investigate the RV functional properties in patients with NAFLD. METHODS: Ninety
      consecutive patients with the diagnosis of biopsy-proven NAFLD and 45 age- and
      sex-matched controls were included. All patients underwent an echocardiographic
      examination. RV function was evaluated by two-dimensional (2D) speckle-tracking
      echocardiography (STE). RESULTS: Mean fibrosis stage and nonalcoholic
      steatohepatitis (NASH) scores were 1.3 +/- 1.1 and 5.2 +/- 1.6, respectively.
      NAFLD patients displayed decreased RV function compared to controls. NAFLD
      patients with liver fibrosis (67 patients) had significantly lower RV function
      assessed by GLS (global longitudinal strain) compared to patients without liver
      fibrosis (18.9 +/- 3.4% vs. 21.6 +/- 2.3%, P < 0.001). NASH score >=5 was
      associated with lower RV-GLS (18.9 +/- 3.1% vs. 21.0 +/- 3.4%, P = 0.006). NASH
      score inversely correlated with RV-GLS (r = -0.370, P < 0.001) such as patients
      with impaired RV-GLS (<19%) showed significantly higher NASH score compared to
      normal RV-GLS group (5.8 +/- 1.4 vs. 4.8 +/- 1.7, P = 0.009). Logistic regression
      analysis revealed that NASH score was an independent predictor of impaired RV
      function in patients with NAFLD. CONCLUSIONS: Patients with NAFLD have impaired
      RV function. NASH score inversely correlates with RV-GLS and independently
      predicts impaired RV function in patients with NAFLD.

PMID- 26202099
TI  - The image-based alcohol-action implicit association test.
AB  - BACKGROUND AND OBJECTIVES: Previous work has shown that automatic alcohol-action
      associations, assessed by the Implicit Association Test (IAT), may play a role in
      hazardous drinking patterns. The majority of alcohol-related IATs have been
      constructed using verbal stimuli, and even those who have used pictorial stimuli
      have only represented beverage categories with pictures. To assess implicit
      appetitive responses among a broader population of alcohol users, such as those
      who experience limitations reading and understanding English, there may be
      utility in the development of an IAT that utilizes only non-verbal stimuli.
      METHODS: The current study presents an initial effort to develop such a task and
      examine its association with drinking. One hundred and fifty-three university
      students participated individually in a laboratory study in which they first
      completed a pictorial alcohol-specific approach/avoid IAT, followed by self
      report measures of drinking. RESULTS: As hypothesized, negative binomial
      regression analyses showed that IAT scores predicted the number of heavy drinking
      episodes and typical number of drinks per occasion. LIMITATIONS: The use of a
      university student sample for this initial study represents an important
      limitation of this work, which should be addressed in future research.
      CONCLUSIONS: These findings provide initial evidence for the potential use of non
      verbal IATs to assess alcohol-related implicit cognition among adults.
      Implications for the assessment of hazardous drinking behavior across populations
      are discussed.

PMID- 26202100
TI  - Integrated genomic approaches identify major pathways and upstream regulators in
      late onset Alzheimer's disease.
AB  - Previous studies have evaluated gene expression in Alzheimer's disease (AD)
      brains to identify mechanistic processes, but have been limited by the size of
      the datasets studied. Here we have implemented a novel meta-analysis approach to
      identify differentially expressed genes (DEGs) in published datasets comprising
      450 late onset AD (LOAD) brains and 212 controls. We found 3124 DEGs, many of
      which were highly correlated with Braak stage and cerebral atrophy. Pathway
      Analysis revealed the most perturbed pathways to be (a) nitric oxide and reactive
      oxygen species in macrophages (NOROS), (b) NFkB and (c) mitochondrial
      dysfunction. NOROS was also up-regulated, and mitochondrial dysfunction down
      regulated, in healthy ageing subjects. Upstream regulator analysis predicted the
      TLR4 ligands, STAT3 and NFKBIA, for activated pathways and RICTOR for
      mitochondrial genes. Protein-protein interaction network analysis emphasised the
      role of NFKB; identified a key interaction of CLU with complement; and linked
      TYROBP, TREM2 and DOK3 to modulation of LPS signalling through TLR4 and to
      phosphatidylinositol metabolism. We suggest that NEUROD6, ZCCHC17, PPEF1 and
      MANBAL are potentially implicated in LOAD, with predicted links to calcium
      signalling and protein mannosylation. Our study demonstrates a highly injurious
      combination of TLR4-mediated NFKB signalling, NOROS inflammatory pathway
      activation, and mitochondrial dysfunction in LOAD. 

PMID- 26202101
TI  - Better life quality and sexual function in men and their female partners with
      short-segment posterior fixation in the treatment of thoracolumbar junction burst
      fractures.
AB  - PURPOSE: Thoracolumbar junction burst fractures remain a challenging problem due
      to controversy over the treatment choice of short- or long-segment posterior
      fixation. The aim of the present study was to compare life quality and sexual
      function of patients after short- and long-segment posterior fixations in the
      treatment of thoracolumbar junction burst fractures. METHODS: In this
      prospective, randomized study, 24 sexually active male patients diagnosed with
      thoracolumbar junction burst fractures were randomly assigned to either the short
      segment posterior fixation (SSPF) group or the long-segment posterior fixation
      group (LLPF). The exclusion criteria were rheumatological disease and spinal
      surgery history. There were no significant differences in age, body mass index or
      smoking habits between the groups. The life quality score of EQ-5D and the
      International Index of erectile function (IIEF-5) score of male patients and the
      Female Sexual Function Index (FSFI) score of female partners were recorded
      preoperatively and 1 year after surgery. RESULTS: The mean age of patients in the
      SSPF and LSPF groups was 44.58 and 42.92 years, respectively. There were no
      statistically significant differences between the groups in the preoperative EQ
      5D and IIEF-5 scores of male patients and the FSFI score of their partners.
      Postoperatively, the EQ-5D scores (p = 0.011) and IIEF-5 scores (p = 0.000) of
      male patients and the FSFI score of their partners (p = 0.001) were better in the
      short-segment group. CONCLUSIONS: Patients treated with SSPF have better sexual
      function and life quality with their partners compared to those treated with
      LSPF. The main clinical relevance of this study is that the impact of the choice
      of short or long-segment treatment on postoperative sexual function and life
      quality should be considered by surgeons when performing posterior fixation after
      thoracolumbar junction burst fractures.

PMID- 26202102
TI  - GABA-Mediated Inactivation of Medial Prefrontal and Agranular Insular Cortex in
      the Rat: Contrasting Effects on Hunger- and Palatability-Driven Feeding.
AB  - A microanalysis of hunger-driven and palatability-driven feeding was carried out
      after muscimol-mediated inactivation of two frontal regions in rats, the
      agranular/dysgranular insular cortex (AIC) and the ventromedial prefrontal cortex
      (vmPFC). Food and water intake, feeding microstructure, and general motor
      activity were measured under two motivational conditions: food-deprived rats
      given standard chow or ad libitum-fed rats given a palatable chocolate shake.
      Muscimol infusions into the AIC diminished intake, total feeding duration, and
      average feeding bout duration for the palatable-food condition only but failed to
      alter exploratory-like behavior (ambulation or rearing). In contrast, intra-vmPFC
      muscimol infusions did not alter the overall intake of chow or chocolate shake.
      However, these infusions markedly increased mean feeding bout duration for both
      food types and produced a modest but significant reduction of exploratory-like
      behavior. The lengthening of feeding-bout duration and reduction in rearing were
      mimicked by intra-vmPFC blockade of AMPA-type but not NMDA-type glutamate
      receptors. Neither water consumption nor the microstructure of water drinking was
      affected by inactivation of either site. These results indicate a regional
      heterogeneity in frontal control of feeding behavior. Neural processing in AIC
      supports palatability-driven feeding but is not necessary for intake of a
      standard food under a food-restriction condition, whereas ventromedial prefrontal
      cortex, and AMPA signaling therein, modulates the duration of individual feeding
      bouts regardless of motivational context. Results are discussed in the context of
      regionally heterogeneous frontal modulation of two distinct components of feeding
      behavior: reward valuation based upon taste perception (AIC) vs switching between
      ingestive and non-ingestive (eg, exploratory-like) behavioral repertoires
      (vmPFC). 

PMID- 26202103
TI  - Contribution of an SFK-Mediated Signaling Pathway in the Dorsal Hippocampus to
      Cocaine-Memory Reconsolidation in Rats.
AB  - Environmentally induced relapse to cocaine seeking requires the retrieval of
      context-response-cocaine associative memories. These memories become labile when
      retrieved and must undergo reconsolidation into long-term memory storage to be
      maintained. Identification of the molecular underpinnings of cocaine-memory
      reconsolidation will likely facilitate the development of treatments that
      mitigate the impact of cocaine memories on relapse vulnerability. Here, we used
      the rat extinction-reinstatement procedure to test the hypothesis that the Src
      family of tyrosine kinases (SFK) in the dorsal hippocampus (DH) critically
      controls contextual cocaine-memory reconsolidation. To this end, we evaluated the
      effects of bilateral intra-DH microinfusions of the SFK inhibitor, PP2 (62.5 ng
      per 0.5 MUl per hemisphere), following re-exposure to a cocaine-associated
      (cocaine-memory reactivation) or an unpaired context (no memory reactivation) on
      subsequent drug context-induced instrumental cocaine-seeking behavior. We also
      assessed alterations in the phosphorylation state of SFK targets, including
      GluN2A and GluN2B N-methyl-D-aspartate (NMDA) and GluA2 alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid receptor subunits at the putative time of memory
      restabilization and following PP2 treatment. Finally, we evaluated the effects of
      intra-DH PEAQX (2.5 MUg per 0.5 MUl per hemisphere), a GluN2A-subunit-selective
      NMDAR antagonist, following, or in the absence of, cocaine-memory reactivation on
      subsequent drug context-induced cocaine-seeking behavior. GluN2A phosphorylation
      increased in the DH during putative memory restabilization, and intra-DH PP2
      treatment inhibited this effect. Furthermore, PP2-as well as PEAQX-attenuated
      subsequent drug context-induced cocaine-seeking behavior, in a memory
      reactivation-dependent manner, relative to VEH. These findings suggest that
      hippocampal SFKs contribute to the long-term stability of cocaine-related
      memories that underlie contextual stimulus control over cocaine-seeking behavior.

PMID- 26202104
TI  - Neuroimmune Regulation of GABAergic Neurons Within the Ventral Tegmental Area
      During Withdrawal from Chronic Morphine.
AB  - Opioid dependence is accompanied by neuroplastic changes in reward circuitry
      leading to a negative affective state contributing to addictive behaviors and
      risk of relapse. The current study presents a neuroimmune mechanism through which
      chronic opioids disrupt the ventral tegmental area (VTA) dopaminergic circuitry
      that contributes to impaired reward behavior. Opioid dependence was induced in
      rodents by treatment with escalating doses of morphine. Microglial activation was
      observed in the VTA following spontaneous withdrawal from chronic morphine
      treatment. Opioid-induced microglial activation resulted in an increase in brain
      derived neurotrophic factor (BDNF) expression and a reduction in the expression
      and function of the K(+)Cl(-) co-transporter KCC2 within VTA GABAergic neurons.
      Inhibition of microglial activation or interfering with BDNF signaling prevented
      the loss of Cl(-) extrusion capacity and restored the rewarding effects of
      cocaine in opioid-dependent animals. Consistent with a microglial-derived BDNF
      induced disruption of reward, intra-VTA injection of BDNF or a KCC2 inhibitor
      resulted in a loss of cocaine-induced place preference in opioid-naive animals.
      The loss of the extracellular Cl(-) gradient undermines GABAA-mediated
      inhibition, and represents a mechanism by which chronic opioid treatments can
      result in blunted reward circuitry. This study directly implicates microglial
      derived BDNF as a negative regulator of reward in opioid-dependent states,
      identifying new therapeutic targets for opiate addictive behaviors. 

PMID- 26202106
TI  - Progressive retinal atrophy in Shetland sheepdog is associated with a mutation in
      the CNGA1 gene.
AB  - Progressive retinal atrophy (PRA) is the collective name of a class of hereditary
      retinal dystrophies in the dog and is often described as the equivalent of
      retinitis pigmentosa in humans. PRA is characterized by visual impairment due to
      degeneration of the photoreceptors in the retina, usually leading to blindness.
      PRA has been reported in dogs from more than 100 breeds and can be genetically
      heterogeneous both between and within breeds. The disease can be subdivided by
      age at onset and rate of progression. Using genome-wide association with 15
      Shetland Sheepdog (Sheltie) cases and 14 controls, we identified a novel PRA
      locus on CFA13 (Praw  = 8.55 * 10(-7) , Pgenome  = 1.7 * 10(-4) ). CNGA1, which
      is known to be involved in human cases of retinitis pigmentosa, was located
      within the associated region and was considered a likely candidate gene.
      Sequencing of this gene identified a 4-bp deletion in exon 9
      (c.1752_1755delAACT), leading to a frameshift and a premature stop codon. The
      study indicated genetic heterogeneity as the mutation was present in all PRA
      affected individuals in one large family of Shelties, whereas some other cases in
      the studied Sheltie population were not associated with this CNGA1 mutation. To
      our knowledge, this is the first report of a mutation in CNGA1 causing PRA in
      dogs. 

PMID- 26202105
TI  - Protein Expression of Proteasome Subunits in Elderly Patients with Schizophrenia.
AB  - The ubiquitin proteasome system (UPS) is a major regulator of protein processing,
      trafficking, and degradation. While protein ubiquitination is utilized for many
      cellular processes, one major function of this system is to target proteins to
      the proteasome for degradation. In schizophrenia, studies have found UPS
      transcript abnormalities in both blood and brain, and we have previously reported
      decreased protein expression of ubiquitin-associated proteins in brain. To test
      whether the proteasome is similarly dysregulated, we measured the protein
      expression of proteasome catalytic subunits as well as essential subunits from
      proteasome regulatory complexes in 14 pair-matched schizophrenia and comparison
      subjects in superior temporal cortex. We found decreased expression of Rpt1,
      Rpt3, and Rpt6, subunits of the 19S regulatory particle essential for ubiquitin
      dependent degradation by the proteasome. Additionally, the alpha subunit of the
      11S alphabeta regulatory particle, which enhances proteasomal degradation of
      small peptides and unfolded proteins, was also decreased. Haloperidol-treated
      rats did not have altered expression of these subunits, suggesting the changes we
      observed in schizophrenia are likely not due to chronic antipsychotic treatment.
      Interestingly, expression of the catalytic subunits of both the standard and
      immunoproteasome were unchanged, suggesting the abnormalities we observed may be
      specific to the complexed state of the proteasome. Aging has significant effects
      on the proteasome, and several subunits (20S beta2, Rpn10, Rpn13, 11Sbeta, and
      11Sgamma) were significantly correlated with subject age. These data provide
      further evidence of dysfunction of the ubiquitin-proteasome system in
      schizophrenia, and suggest that altered proteasome activity may be associated
      with the pathophysiology of this illness. 

PMID- 26202107
TI  - Injectable Progestin-Only Contraception is Associated With Increased Levels of
      Pro-Inflammatory Cytokines in the Female Genital Tract.
AB  - PROBLEM: Genital inflammatory changes may be a mechanism of increased HIV risk
      among injectable progestin-only contraception (IPC) users. METHOD OF STUDY: We
      conducted a cross-sectional analysis of 376 Kenyan and South African women.
      Genital cytokines and secretory leukocyte peptidase inhibitor concentrations in a
      reference population were compared to IPC users and women with reproductive tract
      infections. RESULTS: No significant variability in marker concentrations was
      observed by age or site. Depot medroxyprogesterone acetate (DMPA) users had
      significantly higher MIP-1alpha, MIP-1beta, IL-6, IL-8, IP-10, and RANTES
      concentrations. Norethisterone oenanthate users had significantly higher IL-6, IL
      8, and RANTES concentrations. Women with sexually transmitted infections had
      variable inflammation, and women with bacterial vaginosis exhibited a mixed
      profile of up and downregulation. CONCLUSION: The finding of substantial mucosal
      inflammation among DMPA users provides evidence which, combined with the results
      of prior studies, suggests that DMPA may create an immune environment conducive
      to HIV target cell recruitment and inhibitory for antiviral activity.

PMID- 26202108
TI  - First Report of Human Infection by Agromyces mediolanus, a Gram-Positive Organism
      Found in Soil.
AB  - We report the first human infection by a member of the Agromyces genus, a group
      of Gram-positive bacteria found in soil. A patient with a long-term venous
      catheter developed bacteremia due to a non-vancomycin-susceptible isolate of
      Agromyces mediolanus. Rapid identification was possible by matrix-assisted laser
      desorption ionization-time of flight mass spectrometry. 

PMID- 26202110
TI  - Whole-Genome Mapping as a Novel High-Resolution Typing Tool for Legionella
      pneumophila.
AB  - Legionella is the causative agent for Legionnaires' disease (LD) and is
      responsible for several large outbreaks in the world. More than 90% of LD cases
      are caused by Legionella pneumophila, and studies on the origin and transmission
      routes of this pathogen rely on adequate molecular characterization of isolates.
      Current typing of L. pneumophila mainly depends on sequence-based typing (SBT).
      However, studies have shown that in some outbreak situations, SBT does not have
      sufficient discriminatory power to distinguish between related and nonrelated L.
      pneumophila isolates. In this study, we used a novel high-resolution typing
      technique, called whole-genome mapping (WGM), to differentiate between
      epidemiologically related and nonrelated L. pneumophila isolates. Assessment of
      the method by various validation experiments showed highly reproducible results,
      and WGM was able to confirm two well-documented Dutch L. pneumophila outbreaks.
      Comparison of whole-genome maps of the two outbreaks together with WGMs of
      epidemiologically nonrelated L. pneumophila isolates showed major differences
      between the maps, and WGM yielded a higher discriminatory power than SBT. In
      conclusion, WGM can be a valuable alternative to perform outbreak investigations
      of L. pneumophila in real time since the turnaround time from culture to
      comparison of the L. pneumophila maps is less than 24 h. 

PMID- 26202109
TI  - Systematic Evaluation of Different Nucleic Acid Amplification Assays for
      Cytomegalovirus Detection: Feasibility of Blood Donor Screening.
AB  - Acute primary cytomegalovirus (CMV) infections, which commonly occur
      asymptomatically among blood donors, represent a significant risk for serious
      morbidity in immunocompromised patients (a major group of transfusion
      recipients). We implemented a routine CMV pool screening procedure for plasma for
      the identification of CMV DNA-positive donors, and we evaluated the sensitivities
      and performance of different CMV DNA amplification systems. Minipools (MPs) of
      samples from 18,405 individual donors (54,451 donations) were screened for CMV
      DNA using the RealStar CMV PCR assay (Altona Diagnostic Technologies), with a
      minimum detection limit of 11.14 IU/ml. DNA was extracted with a high-volume
      protocol (4.8 ml, Chemagic Viral 5K kit; PerkinElmer) for blood donor pool
      screening (MP-nucleic acid testing [NAT]) and with the Nuclisens easyMAG system
      (0.5 ml; bioMerieux) for individual donation (ID)-NAT. In total, six CMV DNA
      positive donors (0.03%) were identified by routine CMV screening, with DNA
      concentrations ranging from 4.35 * 10(2) to 4.30 * 10(3) IU/ml. Five donors
      already showed seroconversion and detectable IgA, IgM, and/or IgG antibody titers
      (IgA(+)/IgM(+)/IgG(-) or IgA(+)/IgM(+)/IgG(+)), and one donor showed no CMV
      specific antibodies. Comparison of three commercial assays, i.e., the RealStar
      CMV PCR kit, the Sentosa SA CMV quantitative PCR kit (Vela Diagnostics), and the
      CMV R-gene PCR kit (bioMerieux), for MP-NAT and ID-NAT showed comparably good
      analytical sensitivities, ranging from 10.23 to 11.14 IU/ml (MP-NAT) or from
      37.66 to 57.94 IU/ml (ID-NAT). The clinical relevance of transfusion-associated
      CMV infections requires further investigation, and the evaluated methods present
      powerful basic tools providing sensitive possibilities for viral testing. The
      application of CMV MP-NAT facilitated the identification of one donor with a
      window-phase donation during acute primary CMV infection. 

PMID- 26202111
TI  - Asymptomatic Leprosy Infection among Blood Donors May Predict Disease Development
      and Suggests a Potential Mode of Transmission.
AB  - Blood donor samples (1,007) were assessed for anti-phenolic glycolipid 1 (PGL-1)
      IgM antibodies and Mycobacterium leprae DNA presence, which had 3.8% and 0.3%
      positivity, respectively. After a 5-year follow-up period, six individuals with
      positive markers developed leprosy, raising the hypothesis that asymptomatic
      infection among blood donors may be an undisclosed mode of leprosy transmission
      via transfusion. 

PMID- 26202112
TI  - Development of a Multilocus Sequence Typing System for Medically Relevant
      Bipolaris Species.
AB  - Multilocus sequence typing (MLST) is the gold standard genotyping technique for
      many microorganisms. This classification approach satisfies the requirements for
      a high-resolution, standardized, and archivable taxonomic system. Here, we
      describe the development of a novel MLST system to assist with the investigation
      of an unusual cluster of surgical site infections caused by Bipolaris spp. in
      postoperative cardiothoracic surgery (POCS) patients during January 2008 to
      December 2013 in the southeastern United States. We also used the same MLST
      system to perform a retrospective analysis on isolates from a 2012 Bipolaris
      endophthalmitis outbreak caused by a contaminated product. This MLST system
      showed high intraspecies discriminatory power for Bipolaris spicifera, B.
      hawaiiensis, and B. australiensis. Based on the relatedness of the isolates, the
      MLST data supported the hypothesis that infections in the POCS cluster were from
      different environmental sources while confirming that the endophthalmitis
      outbreak resulted from a point source, which was a contaminated medication. 

PMID- 26202113
TI  - Comparing Etest and Broth Microdilution for Antifungal Susceptibility Testing of
      the Most-Relevant Pathogenic Molds.
AB  - Invasive mold infections are life-threatening diseases for which appropriate
      antifungal therapy is crucial. Their epidemiology is evolving, with the emergence
      of triazole-resistant Aspergillus spp. and multidrug-resistant non-Aspergillus
      molds. Despite the lack of interpretive criteria, antifungal susceptibility
      testing of molds may be useful in guiding antifungal therapy. The standard broth
      microdilution method (BMD) is demanding and requires expertise. We assessed the
      performance of a commercialized gradient diffusion method (Etest method) as an
      alternative to BMD. The MICs or minimal effective concentrations (MECs) of
      amphotericin B, voriconazole, posaconazole, caspofungin, and micafungin were
      assessed for 290 clinical isolates of the most representative pathogenic molds
      (154 Aspergillus and 136 non-Aspergillus isolates) with the BMD and Etest
      methods. Essential agreements (EAs) within +/-2 dilutions of >=90% between the
      two methods were considered acceptable. EAs for amphotericin B and voriconazole
      were >90% for most potentially susceptible species. For posaconazole, the
      correlation was acceptable for Mucoromycotina but Etest MIC values were
      consistently lower for Aspergillus spp. (EAs of <90%). Excellent EAs were found
      for echinocandins with highly susceptible (MECs of <0.015 MUg/ml) or
      intrinsically resistant (MECs of >16 MUg/ml) strains. However, MEC determinations
      lacked consistency between methods for strains exhibiting mid-range MECs for
      echinocandins. We concluded that the Etest method is an appropriate alternative
      to BMD for antifungal susceptibility testing of molds under specific
      circumstances, including testing with amphotericin B or triazoles for non
      Aspergillus molds (Mucoromycotina and Fusarium spp.). Additional study of
      molecularly characterized triazole-resistant Aspergillus isolates is required to
      confirm the ability of the Etest method to detect voriconazole and posaconazole
      resistance among Aspergillus spp. 

PMID- 26202114
TI  - A Single Nucleotide Polymorphism at the TaqMan Probe-Binding Site Impedes Real
      Time Reverse Transcription-PCR-Based Detection of Norovirus GII.4 Sydney.
AB  - A single nucleotide polymorphism (SNP) in the TaqMan probe-binding site resulted
      in decreased sensitivity of real-time reverse transcription-PCR (RT-rtPCR) for
      detection of norovirus genogroup II genotype 4 (GII.4) Sydney. A new degenerate
      probe was designed that improved the sensitivity of the detection while not
      interfering with the detection of other GII and GI strains. 

PMID- 26202115
TI  - Rapid Identification of Bacteria Directly from Positive Blood Cultures by Use of
      a Serum Separator Tube, Smudge Plate Preparation, and Matrix-Assisted Laser
      Desorption Ionization-Time of Flight Mass Spectrometry.
AB  - We analyzed the matrix-assisted laser desorption ionization-time of flight mass
      spectrometry (MALDI-TOF MS) of smudge plate growth for bacterial identification
      from 400 blood cultures. Ninety-seven percent of Gram-negative bacilli and 85% of
      Gram-positive organisms were correctly identified within 4 h; only eight isolates
      (2.0%) were misidentified. This method provided rapid and accurate microbial
      identification from positive blood cultures. 

PMID- 26202097
TI  - Off-Hour Admission and Outcomes in Patients with Acute Intracerebral Hemorrhage
      in the INTERACT2 Trial.
AB  - BACKGROUND: Conflicting data exist of an association between off-hour (weekend,
      holiday, or night-time) hospital admission and adverse outcome in intracerebral
      hemorrhage (ICH). We determined the association between off-hour admissions and
      poor clinical outcome, and of any differential effect of early intensive blood
      pressure (BP) lowering treatment between off- and on-hour admissions, among
      participants of the Intensive BP Reduction in Acute Cerebral Hemorrhage Trial
      (INTERACT2). METHODS: Subsidiary analysis of INTERACT2, a multinational,
      multicenter, clinical trial of patients with spontaneous ICH with elevated
      systolic BP, randomly assigned to intensive (target systolic BP <140 mm Hg) or
      guideline-based (<180 mm Hg) BP management. Primary outcome was death or major
      disability (modified Rankin scale of 3-6) at 90 days. Off-hour admission was
      defined as night-time (4:30 p.m. to 8:30 a.m.) on weekdays, weekends (Saturday
      and Sunday), and public holidays in each participating country. RESULTS: Of 2,794
      patients with information on the primary outcome, 1,770 (63%) were admitted to
      study centers during off-hours. Off-hour admission was not associated with risk
      of poor outcome at 90 days (53% off-hour vs. 55% on-hour; p = 0.49), even after
      adjustment for comorbid risk factors (odds ratio 0.92; 95% CI 0.76-1.12).
      Consistency exists in the effects of intensive BP lowering between off- and on
      hour admission (p = 0.85 for homogeneity). CONCLUSIONS: Off-hour admission was
      not associated with increased risks of death or major disability among trial
      protocol participants with acute ICH. Intensive BP lowering can provide similar
      treatment effect irrespective of admission hours.

PMID- 26202116
TI  - Limited Variation in BK Virus T-Cell Epitopes Revealed by Next-Generation
      Sequencing.
AB  - BK virus (BKV) infection causing end-organ disease remains a formidable challenge
      to the hematopoietic cell transplant (HCT) and kidney transplant fields. As BKV
      specific treatments are limited, immunologic-based therapies may be a promising
      and novel therapeutic option for transplant recipients with persistent BKV
      infection. Here, we describe a whole-genome, deep-sequencing methodology and
      bioinformatics pipeline that identify BKV variants across the genome and at BKV
      specific HLA-A2-, HLA-B0702-, and HLA-B08-restricted CD8 T-cell epitopes. BKV
      whole genomes were amplified using long-range PCR with four inverse primer sets,
      and fragmentation libraries were sequenced on the Ion Torrent Personal Genome
      Machine (PGM). An error model and variant-calling algorithm were developed to
      accurately identify rare variants. A total of 65 samples from 18 pediatric HCT
      and kidney recipients with quantifiable BKV DNAemia underwent whole-genome
      sequencing. Limited genetic variation was observed. The median number of amino
      acid variants identified per sample was 8 (range, 2 to 37; interquartile range,
      10), with the majority of variants (77%) detected at a frequency of <5%. When
      normalized for length, there was no statistical difference in the median number
      of variants across all genes. Similarly, the predominant virus population within
      samples harbored T-cell epitopes similar to the reference BKV strain that was
      matched for the BKV genotype. Despite the conservation of epitopes, low-level
      variants in T-cell epitopes were detected in 77.7% (14/18) of patients.
      Understanding epitope variation across the whole genome provides insight into the
      virus-immune interface and may help guide the development of protocols for novel
      immunologic-based therapies. 

PMID- 26202117
TI  - Molecular Epidemiology of Mycoplasma pneumoniae: Genotyping Using Single
      Nucleotide Polymorphisms and SNaPshot Technology.
AB  - Molecular typing of Mycoplasma pneumoniae is an important tool for identifying
      grouped cases and investigating outbreaks. In the present study, we developed a
      new genotyping method based on single nucleotide polymorphisms (SNPs) selected
      from the whole-genome sequencing of eight M. pneumoniae strains, using the
      SNaPshot minisequencing assay. Eight SNPs, localized in housekeeping genes,
      predicted lipoproteins, and adhesin P1 genes were selected for genotyping. These
      SNPs were evaluated on 140 M. pneumoniae clinical isolates previously genotyped
      by multilocus variable-number tandem-repeat analysis (MLVA-5) and adhesin P1
      typing. This method was also adapted for direct use with clinical samples and
      evaluated on 51 clinical specimens. The analysis of the clinical isolates using
      the SNP typing method showed nine distinct SNP types with a Hunter and Gaston
      diversity index (HGDI) of 0.836, which is higher than the HGDI of 0.583 retrieved
      for the MLVA-4 typing method, where the nonstable Mpn1 marker was removed. A
      strong correlation with the P1 adhesin gene typing results was observed. The
      congruence was poor between MLVA-5 and SNP typing, indicating distinct genotyping
      schemes. Combining the results increased the discriminatory power. This new
      typing method based on SNPs and the SNaPshot technology is a method for rapid M.
      pneumoniae typing directly from clinical specimens, which does not require any
      sequencing step. This method is based on stable markers and provides information
      distinct from but complementary to MLVA typing. The combined use of SNPs and MLVA
      typing provides powerful discrimination of strains. 

PMID- 26202118
TI  - Development of a Multilocus Sequence Typing Scheme for Molecular Typing of
      Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae is a major human respiratory pathogen causing both upper
      and lower respiratory disease in humans of all ages, and it can also result in
      other serious extrapulmonary sequelae. A multilocus sequence typing (MLST) scheme
      for M. pneumoniae was developed based on the sequences of eight housekeeping
      genes (ppa, pgm, gyrB, gmk, glyA, atpA, arcC, and adk) and applied to 55 M.
      pneumoniae clinical isolates and the two type strains M129 and FH. A total of 12
      sequence types (STs) resulted for 57 M. pneumoniae isolates tested, with a
      discriminatory index of 0.21 STs per isolate. The MLST loci used in this scheme
      were shown to be stable in 10 strains following 10 sequential subculture
      passages. Phylogenetic analysis of concatenated sequences of the eight loci
      indicated two distinct genetic clusters that were directly linked to multilocus
      variable-number tandem repeat analysis (MLVA) type. Genetic MLST clustering was
      confirmed by genomic sequence analysis, indicating that the MLST scheme developed
      in this study is representative of the genome. Furthermore, this MLST scheme was
      shown to be more discriminatory than both MLVA and P1 typing for the M.
      pneumoniae isolates examined, providing a method for further and more detailed
      analysis of observed epidemic peaks of M. pneumoniae infection. This scheme is
      supported by a public Web-based database (http://pubmlst.org/mpneumoniae). 

PMID- 26202119
TI  - Ultradeep Sequencing for Detection of Quasispecies Variants in the Major
      Hydrophilic Region of Hepatitis B Virus in Indonesian Patients.
AB  - Quasispecies of hepatitis B virus (HBV) with variations in the major hydrophilic
      region (MHR) of the HBV surface antigen (HBsAg) can evolve during infection,
      allowing HBV to evade neutralizing antibodies. These escape variants may
      contribute to chronic infections. In this study, we looked for MHR variants in
      HBV quasispecies using ultradeep sequencing and evaluated the relationship
      between these variants and clinical manifestations in infected patients. We
      enrolled 30 Indonesian patients with hepatitis B infection (11 with chronic
      hepatitis and 19 with advanced liver disease). The most common
      subgenotype/subtype of HBV was B3/adw (97%). The HBsAg titer was lower in
      patients with advanced liver disease than that in patients with chronic
      hepatitis. The MHR variants were grouped based on the percentage of the viral
      population affected: major, >=20% of the total population; intermediate, 5% to
      <20%; and minor, 1% to <5%. The rates of MHR variation that were present in the
      major and intermediate viral population were significantly greater in patients
      with advanced liver disease than those in chronic patients. The most frequent MHR
      variants related to immune evasion in the major and intermediate populations were
      P120Q/T, T123A, P127T, Q129H/R, M133L/T, and G145R. The major population of MHR
      variants causing impaired of HBsAg secretion (e.g., G119R, Q129R, T140I, and
      G145R) was detected only in advanced liver disease patients. This is the first
      study to use ultradeep sequencing for the detection of MHR variants of HBV
      quasispecies in Indonesian patients. We found that a greater number of MHR
      variations was related to disease severity and reduced likelihood of HBsAg titer.

PMID- 26202120
TI  - Development and Validation of Digital Enzyme-Linked Immunosorbent Assays for
      Ultrasensitive Detection and Quantification of Clostridium difficile Toxins in
      Stool.
AB  - The currently available diagnostics for Clostridium difficile infection (CDI)
      have major limitations. Despite mounting evidence that toxin detection is
      paramount for diagnosis, conventional toxin immunoassays are insufficiently
      sensitive and cytotoxicity assays too complex; assays that detect toxigenic
      organisms (toxigenic culture [TC] and nucleic acid amplification testing [NAAT])
      are confounded by asymptomatic colonization by toxigenic C. difficile. We
      developed ultrasensitive digital enzyme-linked immunosorbent assays (ELISAs) for
      toxins A and B using single-molecule array technology and validated the assays
      using (i) culture filtrates from a panel of clinical C. difficile isolates and
      (ii) 149 adult stool specimens already tested routinely by NAAT. The digital
      ELISAs detected toxins A and B in stool with limits of detection of 0.45 and 1.5
      pg/ml, respectively, quantified toxins across a 4-log range, and detected toxins
      from all clinical strains studied. Using specimens that were negative by
      cytotoxicity assay/TC/NAAT, clinical cutoffs were set at 29.4 pg/ml (toxin A) and
      23.3 pg/ml (toxin B); the resulting clinical specificities were 96% and 98%,
      respectively. The toxin B digital ELISA was 100% sensitive versus cytotoxicity
      assay. Twenty-five percent and 22% of the samples positive by NAAT and TC,
      respectively, were negative by the toxin B digital ELISA, consistent with the
      presence of organism but minimal or no toxin. The mean toxin levels by digital
      ELISA were 1.5- to 1.7-fold higher in five patients with CDI-attributable severe
      outcomes, versus 68 patients without, but this difference was not statistically
      significant. Ultrasensitive digital ELISAs for the detection and quantification
      of toxins A and B in stool can provide a rapid and simple tool for the diagnosis
      of CDI with both high analytical sensitivity and high clinical specificity. 

PMID- 26202121
TI  - Human Wound Infection with Mannheimia glucosida following Lamb Bite.
AB  - Mannheimia spp. are veterinary pathogens that can cause mastitis and pneumonia in
      domestic cattle and sheep. While Mannheimia glucosida can be found as normal
      flora in oral and respiratory mucosa in sheep, there have been no reported cases
      of human infection with this organism. 

PMID- 26202122
TI  - Outbreak of Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniae:
      Are We at the End of the Road?
AB  - Carbapenem-resistant Klebsiella pneumoniae strains that produce K. pneumoniae
      carbapenemase (KPC) have spread globally in the last decade. Colistin is a key
      agent in treating infections caused by this pathogen. In this issue of the
      Journal of Clinical Microbiology, Giani et al. (T. Giani, F. Arena, G. Vaggelli,
      V. Conte, A Chiarell, L. H. De Angelis, R. Fornaini, M. Grazzini, F. Niccolini,
      P. Pecile, and G. M. Rossolini, J Clin Microbiol 53:3341-3344, 2015,
      http://dx.doi.org/10.1128/JCM.01017-15) describe a sustained outbreak of colistin
      resistant KPC-producing K. pneumoniae. 

PMID- 26202123
TI  - Reevaluation of an Acanthamoeba Molecular Diagnostic Algorithm following an
      Atypical Case of Amoebic Keratitis.
AB  - Amoebic keratitis (AK) is a potentially blinding infection, the prompt diagnosis
      of which is essential for limiting ocular morbidity. We undertook a quality
      improvement initiative with respect to the molecular detection of acanthamoebae
      in our laboratory because of an unusual case of discordance. Nine ATCC strains of
      Acanthamoeba and 40 delinked, biobanked, surplus corneal scraping specimens were
      analyzed for the presence of acanthamoebae with four separate real-time PCR
      assays. The assay used by the Free-Living and Intestinal Amebas Laboratory of the
      CDC was considered the reference standard, and the performance characteristics of
      each individual assay and pairs of assays were calculated. Outcome measures were
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV). Of 49 included specimens, 14 (28.6%) were positive by the
      gold standard assay, and 35 (71.4%) were negative. The sensitivities of the
      individual assays ranged from 64.3% to 92.9%, compared to the gold standard,
      while the specificities ranged from 88.6% to 91.4%. The PPVs and NPVs ranged from
      69.2% to 78.6% and from 86.1% to 96.9%, respectively. Combinations of assay pairs
      led to improved performance, with sensitivities ranging from 92.9% to 100% and
      specificities ranging from 97.1% to 100%. ATCC and clinical strains of
      Acanthamoeba that failed to be detected by certain individual assays included
      Acanthamoeba castellanii, Acanthamoeba culbertsoni, and Acanthamoeba lenticulata.
      For three clinical specimens, false negativity of the gold standard assay could
      not be excluded. Molecular diagnostic approaches, especially combinations of
      highly sensitive and specific assays, offer a reasonably performing, operator
      independent, rapid strategy for the detection of acanthamoebae in clinical
      specimens and are likely to be more practical than either culture or direct
      microscopic detection. 

PMID- 26202124
TI  - Large Nosocomial Outbreak of Colistin-Resistant, Carbapenemase-Producing
      Klebsiella pneumoniae Traced to Clonal Expansion of an mgrB Deletion Mutant.
AB  - We describe a large hospital outbreak (93 bloodstream infections) of colistin
      resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae
      isolates which was mirrored by increased colistin consumption. The outbreak was
      mostly traced to the clonal expansion of an mgrB deletion mutant of an ST512
      strain that produced KPC-3. 

PMID- 26202125
TI  - Superbugs on Duodenoscopes: the Challenge of Cleaning and Disinfection of
      Reusable Devices.
AB  - Inadequate flexible endoscope reprocessing has been associated with infection
      outbreaks, most recently caused by carbapenem-resistant Enterobacteriaceae.
      Lapses in essential device reprocessing steps such as cleaning,
      disinfection/sterilization, and storage have been reported, but some outbreaks
      have occurred despite claimed adherence to established guidelines. Recommended
      changes in these guidelines include the use of sterilization instead of high
      level disinfection or the use of routine microbial culturing to monitor efficacy
      of reprocessing. This review describes the current standards for endoscope
      reprocessing, associated outbreaks, and the complexities associated with both
      microbiological culture and sterilization approaches to mitigating the risk of
      infection associated with endoscopy. 

PMID- 26202127
TI  - Features of electrocoagulation syndrome after endoscopic submucosal dissection
      for colorectal neoplasm.
AB  - BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a promising
      treatment for large gastrointestinal superficial neoplasms, although it is
      technically difficult, and perforation and delayed bleeding are well-known
      adverse events. However, there have been no large studies about
      electrocoagulation syndrome after colorectal ESD. The aim of this study was to
      evaluate the incidence and clinical significant risk factors of post-ESD
      coagulation syndrome (PECS). METHODS: This was a retrospective cohort study
      conducted in a referral cancer center. A total of 336 patients with colorectal
      neoplasms (143 adenomas or serrated lesions and 193 carcinomas) underwent ESD
      from January 2011 to June 2013. Incidence, outcome, and factors associated with
      occurrence of PECS were investigated. RESULTS: Occurred in 32 patients (9.5%).
      The median time until PECS was 15.5 h, and the median period of PECS was 32.5 h.
      Fever (>=37.6  degrees C) after ESD was found in 41% of the PECS group and 9% of
      the non-PECS group (P < 0.001). All PECS cases were managed conservatively. On
      multivariate analysis, female patients (odds ratio [OR] = 3.2, P = 0.002), lesion
      location at ascending colon and cecum (OR = 3.5, P = 0.001), and resected
      specimen >=40 mm (OR = 2.1, P = 0.05) were independent risk factors for PECS.
      CONCLUSIONS: Occurred in 32 patients (9.5%) with colorectal ESD; however, all
      cases had a good outcome with conservative management. Female sex, tumor location
      at the ascending colon and cecum, and resected specimen >=40 mm were
      independently significant risk factors for PECS.

PMID- 26202126
TI  - Characterization of Hepatitis C Virus Recombination in Cameroon by Use of
      Nonspecific Next-Generation Sequencing.
AB  - The importance of recombination in the evolution and genetic diversity of the
      hepatitis C virus (HCV) is currently uncertain. Only a small number of
      intergenotypic recombinants have been identified so far, and each has core and
      envelope genes classified as belonging to genotype 2. Here, we investigated two
      putative genotype 4/1 recombinants from southern Cameroon using a number of
      approaches, including standard Sanger sequencing, genotype-specific PCR
      amplification, and non-HCV-specific Illumina RNA sequencing (RNA-seq).
      Recombination between genotypes 1 and 4 was confirmed in both samples, and the
      parental lineages of each recombinant belong to HCV subtypes that are
      cocirculating at a high prevalence in Cameroon. Using the RNA-seq approach, we
      obtained a complete genome for one sample, which contained a recombination
      breakpoint at the E2/P7 gene junction. We developed and applied a new method,
      called Deep SimPlot, which can be used to visualize and identify viral
      recombination directly from the short sequence reads created by next-generation
      sequencing in conjunction with a consensus sequence. 

PMID- 26202129
TI  - The wisdom of patients and families: ignore it at our peril.

PMID- 26202128
TI  - Psychosocial factors that influence men's help-seeking for cancer symptoms: a
      systematic synthesis of mixed methods research.
AB  - OBJECTIVE: Effectiveness of cancer control partly depends upon early
      identification and treatment. Men appear to be more likely to delay help-seeking
      for symptoms, resulting in later diagnosis. This review aims to provide a mixed
      research synthesis of the psychosocial barriers to and facilitators of help
      seeking for cancer symptoms among men. METHODS: Systematic methods were followed,
      including a predefined research question and search strategy. Searches retrieved
      7131 international records from online databases: MEDLINE (n = 3011), PubMed (n =
      471), SCOPUS (n = 896), Informit (n = 131), PsychINFO (n = 347), and Web of
      Science (n = 2275). Forty studies were eligible for inclusion in the review (25
      qualitative studies, 11 quantitative studies, and 4 mixed-method studies).
      RESULTS: There was strong observational evidence for several psychosocial
      barriers to men's help-seeking behaviour: low cancer knowledge and inaccurate
      symptom interpretation, embarrassment and fear, and conformity to masculine
      gender role norms. The strongest facilitating factor associated with men's help
      seeking behaviour was encouragement and support of spouses and family members.
      The majority of research was qualitative and used small samples, making
      generalisations to the wider population difficult. CONCLUSIONS: Men's help
      seeking for cancer symptoms is influenced by several psychosocial factors, which,
      in part, may be gender-specific. Health promotion initiatives to improve help
      seeking behaviour among men should aim to increase cancer knowledge, reduce
      embarrassment and fear, address social norms deterring timely help-seeking, and
      acknowledge informal help-seeking with spouses and family members. Increasing the
      theoretical grounding of research could aid cohesion across the research area and
      the design of effective health promotion interventions. Copyright (c) 2015 John
      Wiley & Sons, Ltd.

PMID- 26202130
TI  - Exploring the impact of consultants' experience on hospital mortality by day of
      the week: a retrospective analysis of hospital episode statistics.
AB  - OBJECTIVE: To examine the association of consultants' experience with mortality
      by day of the week when elective surgery was performed. DESIGN: Retrospective
      observational study using English hospital administrative data. SETTING: All
      acute and specialist English National Health Service (NHS) hospitals carrying out
      elective surgery between financial years 2008-2009 and 2010-2011. PARTICIPANTS:
      Patients undergoing elective surgical procedures. MAIN OUTCOME MEASURES: Death in
      or out of hospital within 30 days of the surgical procedure taking place.
      RESULTS: We examined 3 922 091 (26 409 deaths) elective procedures with valid
      consultant information between 2008-2009 and 2010-2011 in English hospitals;
      there were 21 196 consultants in charge of these procedures, which took place in
      163 NHS hospitals. Consultant seniority had no significant impact in predicting
      mortality (p=0.345). Patients undergoing elective surgery under junior
      consultants had slightly lower odds of 30-day death when compared with patients
      under more experienced consultants (OR 0.95, 95% CI 0.91 to 0.99). We found
      significant mortality variation among consultants in charge of elective
      procedures within hospitals, with only moderate variation between hospitals. The
      adjusted odds of death remained higher for Friday (OR 1.48, 95% CI 1.42 to 1.54),
      Saturday (OR 1.97, 95% CI 1.83 to 2.12) and Sunday (OR 1.67, 95% CI 1.50 to 1.85)
      after adjusting for consultant seniority and patient characteristics. Consultant
      experience is significantly lower (p<0.0001) on a Friday (median (SD) was 7.9
      years (4.4)) than the Monday to Thursday average (median (SD) was 8.5 years
      (4.3)). CONCLUSIONS: Our cohort of patients shows that consultant seniority is
      not a significant factor in predicting 30-day mortality following elective
      surgery by day of the week. The end-of-the-week effect remains significant after
      adjusting for patient, consultant and hospital effects, suggesting that other
      unobserved factors may be driving the higher mortality towards the end of the
      week. Consultant's years of experience are lowest on a Friday; however, we do not
      believe that this small variation has any impact on patient outcomes.

PMID- 26202131
TI  - Providers contextualise care more often when they discover patient context by
      asking: meta-analysis of three primary data sets.
AB  - OBJECTIVES: One important component of patient-centred care is provider
      incorporation of patient contextual factors-life circumstances relevant to their
      care-in managing the patient's health. The current study uses data sets collected
      from direct observation of care to examine if how a provider learns contextual
      information influences whether the provider incorporates the information into a
      care plan. METHODS: Three data sets were reanalysed: a research study with
      physicians, a quality improvement project with physicians and a performance
      measurement project with telephone health assistants. In each data set,
      investigators compute rates of incorporation of patient contextual factors into
      the care plan for encounters in which factors were elicited in response to a
      probe by the provider versus revealed spontaneously by the patient. We report the
      rates, CIs and associated ORs for each study and overall using a random effects
      meta-analysis. RESULTS: Providers elicited 57%, 49% and 30% of patient contextual
      factors identified in encounters in each data set. Patient contextual factors
      identified in response to probes were incorporated into the plan of care more
      frequently than those revealed spontaneously by patients (68% vs 46%, 71% vs 54%
      and 93% vs 77%, respectively). The summary OR for incorporation of patient
      contextual factors into the care plan when the factor was probed versus revealed
      spontaneously was 4.16 (95% CI 2.0 to 8.6). While this estimate was associated
      with significant heterogeneity (I(2)=76%), the ORs for the individual data sets
      were 2.53 (1.4 to 4.5), 6.25 (4.9 to 8.0) and 4.2 (0.9 to 19.3). CONCLUSIONS: In
      encounters where addressing patient contextual factors may play an important role
      in care decisions, factors that are elicited actively by the provider are more
      likely to be incorporated in the care plan than factors revealed spontaneously by
      the patient. These differences in the care process associated with provider
      performance can only be demonstrated through direct observation.

PMID- 26202133
TI  - Abstracts-APASL 2013.

PMID- 26202134
TI  - Gelatin Effects on the Physicochemical and Hemocompatible Properties of
      Gelatin/PAAm/Laponite Nanocomposite Hydrogels.
AB  - In recent years, inorganic nanoparticles such as Laponite have frequently been
      incorporated into polymer matrixes to obtain nanocomposite hydrogels with
      hierarchical structures, ultrastrong tensibilities, and high transparencies.
      Despite their unique physical and chemical properties, only a few reports have
      evaluated Laponite-based nanocomposite hydrogels for biomedical applications.
      This article presents the synthesis and characterization of a novel,
      hemocompatible nanocomposite hydrogels by in situ polymerization of acrylamide
      (AAm) in a mixed suspension containing Laponite and gelatin. The compatibility,
      structure, thermal stability, and mechanical properties of the resulting NC gels
      with varied gel compositions were investigated. Our results show that the
      prepared nanocomposite hydrogels exhibit good thermal stability and mechanical
      properties. The introduction of a biocompatible polymer, gelatin, into the
      polymer matrix did not change the transparency and homogeneity of the resulting
      nanocomposite hydrogels, but it significantly decreased the hydrogel's pH
      responsive properties. More importantly, gelatins that were incorporated into the
      PAAm network resisted nonspecific protein adsorption, improved the degree of
      hemolysis, and eventually prolonged the clotting time, indicating that the in
      vitro hemocompatibility of the resulting nanocomposite hydrogels had been
      substantially enhanced. Therefore, these nanocomposite hydrogels provide
      opportunities for potential use in various biomedical applications. 

PMID- 26202132
TI  - Serum lipid expression correlates with function and regeneration following living
      donor liver transplantation.
AB  - Following living donor liver transplantation (LDLT; and unlike deceased donor
      liver transplantation [DDLT]), the liver must rapidly regenerate, and sometimes
      segmental graft dysfunction (SGD) is observed. Hepatic regeneration requires
      substantial de novo lipid synthesis, and we previously reported that expression
      of lipid-related genes is dysregulated in LDLT. Here, we compare serum lipid
      measurements in 41 LDLT recipients and 43 DDLT recipients at baseline and at
      serial posttransplant time points. In addition, we examined whether serum
      lipid/apolipoprotein (apo) levels correlate with the degree of liver regeneration
      (measured using percent volume increase [%VI] at 3 months) or SGD in LDLT
      recipients. In contrast to DDLT, lipid levels declined early after LDLT but
      returned to baseline by 30 days. The odds ratio (OR) for achieving robust
      regeneration (>90 %VI) was 2.53 (95% confidence interval [CI], 1.15-5.52) for
      every 1 mg/dL increase in serum apoE at 30 days. The OR of SGD for every year
      increase in donor age was 1.19 (95% CI, 1.02-1.39), and 0.61 for every 1 mg/dL
      increase in serum high-density lipoprotein cholesterol at 7 days (95% CI, 0.34
      1.11). No associations were detected between preoperative serum lipids/apos in
      LDLT donors and SGD or %VI in recipients. In conclusion, we suggest that
      initiation of regeneration prevents the liver from participating fully in lipid
      transport and metabolism. Inability to meet systemic metabolic needs may result
      in compromised liver function and SGD. Certain serum lipid concentrations
      correlate with extent of liver regeneration and function.

PMID- 26202135
TI  - Perinatal outcomes of patients who achieved pregnancy with a morphologically poor
      embryo via assisted reproductive technology.
AB  - PURPOSE: To learn more about the perinatal outcomes of conception via the use of
      low-grade embryos, we evaluated the relationship between the status of
      transferred embryos and the resultant perinatal outcomes. METHODS: A total of 340
      patients who achieved pregnancy via ART treatment and consequently delivered in
      our clinic between April 2009 and March 2014 were recruited for this study.
      Patients were divided into two groups according to a morphological assessment of
      the transferred embryos, which relegated 79 patients into a poor-embryo group
      with the remainders (n = 261) placed into a good-embryo group. RESULTS: The mean
      maternal age for the poor-embryo group was 36.0 years, which was similar to the
      good-embryo group (36.8). In both groups, the percentages of fresh ET cycles were
      similar. The values for the mean birth weight and birth height of infants in the
      poor-embryo group were 3055 g and 50.3 cm, respectively, and there were no
      significant differences with the good-embryo group. The umbilical blood gas
      analysis in the poor-quality group was similar to that in the good-embryo group.
      There were no obvious major anomalies among the infants of either group.
      CONCLUSIONS: The perinatal outcomes of the poor-embryo group were comparable to
      those of the good-embryo group. Based on these results, we can provide qualified
      assurance for a normal perinatal outcome to patients who had no choice but to
      undergo embryo transfer with a poor-quality embryo.

PMID- 26202136
TI  - Cervical screening program and the psychological impact of an abnormal Pap smear:
      a self-assessment questionnaire study of 590 patients.
AB  - PURPOSE: Invasive cervical cancer is today the fourth most common cancer of women
      in western civilization. Screening programs have led to a continuously decrease.
      Nevertheless, both screening and a positive test result are known to be
      associated with a negative psychological impact. Screening programs in European
      countries differ and thus psychological impact might as well. The aim of this
      study was to evaluate the psychological impact of women with an abnormal Pap
      smear in a German cohort. METHODS: Between July 2013 and May 2014, a self
      assessment questionnaire was distributed to 595 patients that were referred to a
      special clinic for cervical dysplasia for further evaluation of an abnormal Pap
      smear. Patients were recruited in five different centers. RESULTS: Most patients
      (45.9 %) were informed about the test result via phone call by their doctor. 68.8
      % of the patients felt anxious and 26.3 % even felt panic. After having talked to
      their physician, 51.4 % of our cohort still felt worried and only 24.4 % felt
      reassured. Concerning disease management, 48.4 % underwent a control Pap smear in
      6 months. The preferred information source was the physician (63.9 %). Compared
      to the results in other European countries, our study cohort showed differences
      concerning age distribution, patients living in a partnership, number of children
      and especially disease management. CONCLUSION: Cancer screening itself and
      abnormal test results have an impact on patient's feelings. To reduce the
      psychological impact, patients need to be better informed about the risks and
      benefits of cancer screening programs and in case of cervical cancer screening
      about the meaning of an abnormal test result. Our results underline the
      importance of a trustful physician-patient relationship in that matter.

PMID- 26202137
TI  - Renal cancer in kidney transplanted patients.
AB  - Renal cancer occurs more frequently in renal transplanted patients than in the
      general population, affecting native kidneys in 90% of cases and the graft in 10
      %. In addition to general risk factors, malignancy susceptibility may be
      influenced by immunosuppressive therapy, the use of calcineurin inhibitors (CNI)
      as compared with mammalian target of rapamycin inhibitors, and the length of
      dialysis treatment. Acquired cystic kidney disease may increase the risk for
      renal cancer after transplantation, while autosomal dominant polycystic kidney
      disease does not seem to predispose to cancer development. Annual ultrasound
      evaluation seems appropriate in patients with congenital or acquired cystic
      disease or even a single cyst in native kidneys, and every 2 years in patients
      older than 60 years if they were on dialysis for more than 5 years before
      transplantation. Immunosuppression should be lowered in patients who develop
      renal cancer, by reduction or withdrawal of CNI. Although more evidence is still
      needed, it seems reasonable to shift patients from CNI to everolimus or sirolimus
      if not already treated with one of these drugs, with due caution in subjects with
      chronic allograft nephropathy.

PMID- 26202139
TI  - Avascular necrosis complicating chondral resurfacing techniques.
AB  - Autologous chondrocyte implantation (ACI) and mosaicplasty have become
      established operations used to treat full-thickness chondral lesions in the knee
      and elsewhere. Although complications of both have been documented, there are no
      previous reports of avascular necrosis (AVN) complicating these procedures.
      Awareness of AVN as a complication of ACI might have prompted an earlier
      diagnosis, with possible non-surgical treatment or more minor surgery being
      possible. At the very least, an appropriate form of management could have been
      initiated earlier, so shortening the period of disability and suffering for the
      patient. 

PMID- 26202138
TI  - Revision anterior cruciate ligament reconstruction: clinical outcome and evidence
      for return to sport.
AB  - PURPOSE: An increasing number of patients undergo revision anterior cruciate
      ligament (ACL) reconstruction, with the intention of returning to sport being a
      major indication. The aim of this study is to assess the available evidence for
      clinical improvement and return to sport, to understand the real potential of
      this procedure in regaining functional activity, and to facilitate improved
      counselling of patients regarding the expected outcome after revision ACL
      reconstruction. METHODS: The search was conducted on the PubMed database.
      Articles reporting clinical results for revision ACL reconstruction were
      included. A meta-analysis was performed on return to sport, and results were
      compared to the literature on primary ACL reconstruction. Other specific clinical
      outcomes (Lysholm, Tegner, IKDC Objective scores) were also included in the meta
      analysis. RESULTS: Of the 503 identified records, a total of 59 studies involving
      5365 patients were included in the qualitative data synthesis. Only 31 articles
      reported the rate of return to sport. Whereas 73 % of good objective results and
      satisfactory subjective results were documented, 57 % of patients did not return
      to the same level of sport activity, significantly inferior to that of a primary
      procedure. CONCLUSION: The real potential of revision ACL reconstruction should
      not be overestimated due to the low number of patients able to return to their
      previous activity level, significantly inferior with respect to that reported for
      primary ACL reconstruction. This finding will help physicians in the clinical
      practice providing realistic expectations to the patients. Future studies should
      focus on participation-based outcome measures such as return to sport and in
      strategies to improve the results in terms of return to previous activities after
      revision ACL reconstruction. LEVEL OF EVIDENCE: Systematic review and meta
      analysis including Level IV studies, Level IV.

PMID- 26202140
TI  - Prediction of semitendinosus-gracilis graft diameter in children and adolescents
      using anthropometric measures.
AB  - PURPOSE: The aim of this study was to evaluate whether the anthropometric and
      demographic measures of patients under 18 years can be used to predict the
      diameter of STG autograft in ACL reconstruction surgery. METHODS: Retrospective
      series of 169 patients under 18 years (112 men, 57 women, average age 15.8 years)
      underwent ACL reconstruction surgery with STG autograft. We recorded
      anthropometric measures (weight, height and BMI), demographics (age and gender)
      and autograft diameter used. Correlation coefficients, linear regression and
      unpaired t test were used to determine the relationship between
      anthropometric/demographic variables and the diameter of the graft. p values
      <0.05 were considered statistically significant. RESULTS: Correlation analysis
      showed a significant positive relation between height and graft diameter (r =
      0.483, p < 0.0001) as well as between weight and graft diameter (r = 0.248, p =
      0.001). However, age and BMI did not correlate with graft thickness (r = 0.098
      and p = 0.203, r = 0.009 and p = 0.905, respectively). The mean graft diameter in
      men was 8.2 (range 6-10) and 7.5 in women (range 6-9), a difference that was
      statistically significant (p < 0.001). CONCLUSIONS: Prediction of the STG graft
      diameter according to the height of the patient is an easy and reliable method in
      children and adolescents. These data may provide relevant preoperative
      information about the need of an alternative graft source and can be useful when
      counselling patients. LEVEL OF EVIDENCE: IV.

PMID- 26202141
TI  - Cryopreserved Subcutaneous Adipose Tissue for Fat Graft.
AB  - Cryopreservation of subcutaneous white adipose tissue (sWAT) avoids multiple
      surgeries in patients subjected to reconstructive procedure. Fat grafts were
      performed subcutaneously on 26 mice treated with fresh (13 mice) or cryopreserved
      (13 mice) human sWAT. Cytofluorometry for CD marker expression of stem cells,
      differentiation capability, and in vivo survival of fat grafts were evaluated. In
      vitro analysis evidenced that cryopreservation did not affect the stem potential
      of samples. In vivo MRI showed that grafts were well preserved in 13 mice treated
      with fresh sWAT, whereas in 13 animals treated with thawed fat, graft volumes
      were strongly reduced after 1 week. Ultrastructural studies performed both on
      fresh and thawed specimens demonstrated that grafts performed with thawed sWAT
      are able to store lipids more slowly with respect to grafts performed with fresh
      sWAT and adipocytes maintained a multilocular appearance. Collected data
      demonstrated that the protocol of cryopreservation could maintain the
      regenerative capability of the sWAT, but the rate of reabsorption after fat
      grafting is higher using cryopreserved sWAT. Maintaining the stem potential of
      sWAT after cryopreservation is a very important aspect for reconstructive and
      regenerative medicine. The employment of cryopreserved sWAT represents an
      interesting goal for surgeons. Surely there is the necessity to improve the
      protocol of cryopreservation. NO LEVEL ASSIGNED: This journal requires that
      authors assign a level of evidence to each submission to which Evidence-Based
      Medicine rankings are applicable. This excludes Review Articles, Book Reviews,
      and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and
      Experimental Studies. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors http://www.springer.com/00266 .

PMID- 26202142
TI  - Thrombocytosis and Raised CRP Levels Predicts Advanced Stage in Esophageal
      Carcinoma.
AB  - PURPOSE: The significance of thrombocytosis and raised C-reactive protein (CRP)
      as prognostic markers in esophageal cancer is unclear. METHODS: We prospectively
      studied 50 consecutive patients with esophageal cancer and analyzed the relation
      of preoperative platelet count and CRP levels with the clinico-pathological
      characteristics and stage of the disease. The platelet count of 319 * 10(9)/L for
      thrombocytosis and CRP level >6 mg/dl were taken as cut-off values. RESULTS: The
      incidence of thrombocytosis as well as raised CRP level was 50 %. Eighty percent
      of patients with thrombocytosis had raised CRP levels. None of patients with
      early disease (stage I) had thrombocytosis while patients with advanced stage
      were associated with thrombocytosis, 81.81 % in stage III and 100 % in stage IV
      (p < 0.001). The incidence of elevated CRP levels has shown progressive linear co
      relation with the stage of carcinoma, i.e., 0 % in pathological stage I, 16.67 %
      in stage II, 45.45 % in stage III, and 100 % in stage IV disease (p = 0.011).
      Patients with thrombocytosis and patients with raised CRP were associated with
      pathological nodal metastases in 84.61 % cases (p 0.005) and 61.53 % (p 0.030),
      respectively. CONCLUSION: Thrombocytosis alone or in combination with raised CRP
      had progressive linear relation with the stage of esophageal carcinoma.

PMID- 26202143
TI  - A Novel Serum 4-microRNA Signature for Lung Cancer Detection.
AB  - The aim of this study was to identify differentially-expressed miRNAs in the
      serum of non-small cell lung cancer (NSCLC) patients that might be a clinically
      useful tool for lung cancer early detection. We performed miRNA expression
      profile analysis using TaqMan OpenArray Human panel in a discovery set of 70
      serum samples obtained at lung tumor resection and 22 non-cancer subjects (NC).
      Selected serum miRNAs were then validated by quantitative PCR using an
      independent validation set of serum samples from LC patients (n = 84) and NC (n =
      23). Sixty miRNAs were significantly up-regulated and 31 were down-regulated in
      the serum from NSCLC patients versus NC (adjusted p < 0.001). Four miRNAs (miR
      193b, miR-301, miR-141 and miR-200b) were selected for validating their
      diagnostic value in an independent cohort. In the discovery set, the ROC plot
      derived from the combination of these miRNAs yielded an area under the curve
      (AUC) of 0.985 (95% CI 0.961-1.000, p < 0.001). In the test set, this miRNA
      signature exhibited an AUC of 0.993 (95% CI 0.979-1.000, p < 0.001). In
      conclusion, we identified a serum 4-miRNA signature that discriminated with high
      accuracy lung cancer patients from NC. Further prospective validation of this
      miRNA signature is warranted. 

PMID- 26202144
TI  - Role of mTOR1 and mTOR2 complexes in MEG-01 cell physiology.
AB  - The function of the mammalian target of rapamycin (mTOR) is upregulated in
      response to cell stimulation with growing and differentiating factors. Active
      mTOR controls cell proliferation, differentiation and death. Since mTOR
      associates with different proteins to form two functional macromolecular
      complexes, we aimed to investigate the role of the mTOR1 and mTOR2 complexes in
      MEG-01 cell physiology in response to thrombopoietin (TPO). By using mTOR
      antagonists and overexpressing FKBP38, we have explored the role of both mTOR
      complexes in proliferation, apoptosis, maturation-like mechanisms, endoplasmic
      reticulum-stress and the intracellular location of both active mTOR complexes
      during MEG-01 cell stimulation with TPO. The results demonstrate that mTOR1 and
      mTOR2 complexes play different roles in the physiology of MEG-01 cells and in the
      maturation-like mechanisms; hence, these findings might help to understand the
      mechanism underlying generation of platelets. 

PMID- 26202146
TI  - Autobiography of Branka M. Ladanyi.

PMID- 26202145
TI  - Tribute to Branka M. Ladanyi.

PMID- 26202149
TI  - Publications of Branka M. Ladanyi.

PMID- 26202150
TI  - Follicular and endocrine dose responses according to anti-Mullerian hormone
      levels in IVF patients treated with a novel human recombinant FSH (FE 999049).
AB  - OBJECTIVE: To study the association between serum anti-Mullerian hormone (AMH)
      levels and follicular development and endocrine responses induced by increasing
      doses (5.2-12.1 MUg/day) of a novel recombinant human FSH (rhFSH, FE 999049) in
      patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection
      (ICSI) in a GnRH antagonist protocol. DESIGN: Secondary analysis of a randomized
      controlled trial with stratified randomization according to AMH (lower stratum:
      5.0-14.9 pmol/l; higher stratum: 15.0-44.9 pmol/l). PATIENTS: Infertile women of
      good prognosis (n = 265). MEASUREMENTS: Follicular development and endocrine
      parameters during controlled ovarian stimulation (COS) with rhFSH. RESULTS: Serum
      FSH levels increased with increasing rhFSH doses and steady-state levels for each
      dose were similar in both AMH strata. In the whole study population, significant
      (P < 0.001) positive dose responses were observed for the number of follicles >=
      12 mm, and serum levels of oestradiol, inhibin B, inhibin A and progesterone at
      end of stimulation. In comparison with the higher AMH stratum, patients in the
      lower AMH stratum had significantly different slopes of the dose-response curves
      for these hormones, and no clear dose-related increase was observed for the
      number of follicles in these patients. CONCLUSIONS: Dose-response relationships
      between rhFSH and follicular development and endocrine parameters are
      significantly different for IVF/ICSI patients with lower and higher serum AMH
      levels at start of COS.

PMID- 26202151
TI  - Prospective Comprehensive Swallowing Evaluation of Minimally Invasive
      Esophagectomies with Cervical Anastomosis: Silent Versus Vocal Aspiration.
AB  - INTRODUCTION: Pneumonia and tracheal aspiration remain problematic following
      esophagectomy. We hypothesized that the incidence of postesophagectomy pneumonia
      occurs in part because of swallowing dysfunction and more importantly silent
      tracheobronchial aspiration. Therefore, we instituted a routine prospective
      formal swallowing evaluation to determine if the aspiration rate and its
      associated morbidity can be decreased by early identification of patients with
      silent or vocal aspiration. METHODS: Patients undergoing minimally invasive
      McKeown esophagectomy and receiving neoadjuvant chemoradiotherapy (NACR) were
      prospectively enrolled between December 2013 to January 2015. A standardized
      cineradiography observation utilizing the Rosenbek penetration-aspiration (RPA)
      scale was used to rule out anastomotic leak and/or aspiration. RESULTS: Of 27
      patients evaluated, twelve patients were noted to have silent (n = 8) or vocal
      (cough n = 4) aspiration of thin liquid (n = 8) or nectar-thick consistency (n =
      4) on their initial study. Three patients were noted to have an anastomotic leak
      and vocal aspiration on their initial study. Eight of the nine patients who
      aspirated but did not have an anastomotic leak on their initial study had a
      repeat RPA study prior to discharge showing improvement from the initial study.
      Six patients (22 %) had vocal cord paresis and clinical hoarseness, but only two
      patients who had clinical diagnosis of pneumonia were noted to have vocal cord
      paresis and silent aspiration. CONCLUSIONS: Swallowing dysfunction remains a
      common problem after minimally invasive esophagectomy (MIE) with cervical
      anastomosis and can be readily identified. Silent aspiration likely contributes
      to pneumonia after MIE.

PMID- 26202152
TI  - Nurse provision of healthy lifestyle advice to people who are overweight or
      obese.
AB  - A cross-sectional survey was conducted in a regional area in Australia to measure
      nurses' perceptions, practices, and knowledge in regard to providing healthy
      lifestyle advice to people who are overweight or obese. Responses were compared
      between geographic regions. Participation was voluntary and anonymous. Of the 79
      nurse participants, 68% considered that provision of healthy lifestyle advice was
      within their scope of practice. Only 28% reported frequently estimating body mass
      index in the practice setting. Nurses often recommended increasing activity
      levels (44%), but recommended reducing daily caloric intake less often (25%).
      Nurses' knowledge about weight management was variable and the proportion of
      correct answers to knowledge items ranged from 33-99%. Nurses have many
      opportunities to deliver healthy lifestyle advice in a range of practice
      settings. The variation in practices and knowledge of nurses indicates a need for
      improved healthy lifestyle education for undergraduate and practicing nurses. 

PMID- 26202153
TI  - Delay Discounting Mediates Parent-Adolescent Relationship Quality and Risky
      Sexual Behavior for Low Self-Control Adolescents.
AB  - Parent-adolescent relationship quality and delay discounting may play important
      roles in adolescents' sexual decision making processes, and levels of self
      control during adolescence could act as a buffer within these factors. This
      longitudinal study included 219 adolescent (55 % male; mean age = 12.66 years at
      Wave 1; mean age = 15.10 years at Wave 2) and primary caregiver dyads. Structural
      equation modeling (SEM) was utilized to determine whether delay discounting
      mediated the association between parent-adolescent relationship quality and
      adolescents' risky sexual behavior and how this mediated association may differ
      between those with high versus low self-control. The results revealed parent
      adolescent relationship quality plays a role in the development of risky sexual
      behavior indirectly through levels of delay discounting, but only for adolescents
      with low self-control. These findings could inform sex education policies and
      health prevention programs that address adolescent risky sexual behavior. 

PMID- 26202154
TI  - Identification of early environmental risk factors for irritable bowel syndrome
      and dyspepsia.
AB  - BACKGROUND: The role of childhood environment including exposure to infection via
      siblings and pets in irritable bowel syndrome (IBS) and dyspepsia is relatively
      unknown. We assessed proxy measures of microbial exposure in early childhood to
      assess if these are associated with IBS and functional dyspepsia in later life.
      METHODS: Participants (n = 767, response rate = 53%) were a random population
      sample from Sydney, Australia who previously responded to a validated survey. IBS
      and functional dyspepsia were defined using Rome III criteria. Early
      environmental risk factors assessed included type of birth delivery, premature
      birth, breastfeeding, bedroom sharing, and pet exposure (the latter two then
      combined as early hygiene factors) up to 5 years of age. Post infectious IBS (PI
      IBS) was assessed by development of IBS following gastroenteritis. KEY RESULTS:
      In this sample, in adult life 17% developed IBS (of which 20% had PI-IBS) and 12%
      functional dyspepsia. Development of IBS was associated with childhood factors-a
      shorter duration of breastfeeding (odds ratios [OR] = 0.87, 95% CI: 0.78-0.97, p
      = 0.01), sharing a bedroom (OR = 1.89, 95% CI: 1.73-3.08, p = 0.01), exposure to
      a herbivore pet (OR = 1.65 (1.10, 2.48), p = 0.02), and hygiene factors (OR =
      4.39; 95% CI: 1.89-10.21, p = 0.001). The sole factor associated with functional
      dyspepsia was exposure to a herbivore pet (1.79; 95% CI: 1.19-2.87, p = 0.02).
      CONCLUSIONS & INFERENCES: Childhood environment factors, particularly bedroom
      sharing and pet exposure, combined with subsequent risk of microbial exposure are
      a risk factor for IBS in later life. These associations however need confirmation
      to rule out any risk of a type I error.

PMID- 26202155
TI  - Strategies to Engage Men and Boys in Violence Prevention: A Global Organizational
      Perspective.
AB  - This study presents descriptive findings from in-depth interviews with 29
      representatives of organizations in Africa, Asia, Europe, Oceania, and North and
      South America that engage men and boys in preventing gender-based violence. In
      particular, the findings suggest that strategies are responsive to the specific
      cultural, economic, and contextual concerns of the local community, with nuanced
      messages and appropriate messengers. In addition, respondents reported key
      principles informing their organizational strategies to deepen men and boys'
      engagement. Attention is also paid to respondents' caution about the risks of
      framing of engagement practices as separate from both women's organizations and
      women and girls themselves. 

PMID- 26202157
TI  - Magnetic stimulation supports muscle and nerve regeneration after trauma in mice.
AB  - INTRODUCTION: Magnetic stimulation (MS) has the ability to induce muscle twitch
      and has long been proposed as a therapeutic modality for skeletal muscle
      diseases. However, the molecular mechanisms underlying its means of action have
      not been defined. METHODS: Muscle regeneration after trauma was studied in a
      standard muscle injury mouse model. The influence of MS on the formation of motor
      units, posttrauma muscle/nerve regeneration, and vascularization was
      investigated. RESULTS: We found that MS does not cause systemic or muscle damage
      but improves muscle regeneration by significantly minimizing the presence of
      inflammatory infiltrate and formation of scars after trauma. It avoids posttrauma
      muscle atrophy, induces muscle hypertrophy, and increases the metabolism and
      turnover of muscle. It triples the expression of muscle markers and significantly
      improves muscle functional recovery after trauma. CONCLUSIONS: Our results
      indicate that MS supports muscle and nerve regeneration by activating muscle
      nerve cross-talk and inducing the maturation of neuromuscular junctions.

PMID- 26202158
TI  - Clinical utility of quantitative bright spots analysis in patients with acute
      coronary syndrome: an optical coherence tomography study.
AB  - To investigate the clinical significance of bright spots in coronary plaque
      detected by optical coherence tomography (OCT) in patients with coronary artery
      disease. We identified 112 patients [acute coronary syndromes (ACS): n = 50,
      stable angina pectoris (SAP): n = 62] who underwent OCT imaging of the culprit
      lesion. A novel OCT algorithm was applied to detect bright spots representing the
      juxtaposition of a variety of plaque components including macrophages. The
      density of bright spots within the most superficial 250 MUm of the vessel wall
      was measured at the site of culprit lesion. Bright spot density in the culprit
      lesion was significantly higher in patients presenting with ACS compared to those
      presenting with SAP (0.51 +/- 0.43% vs. 0.37 +/- 0.26%, P = 0.04), particularly
      in the subgroup with ruptured culprit plaque (0.59 +/- 0.52%). Thin-cap
      fibroatheroma (TCFA) was associated with a trend towards a higher density of
      bright spots compared to non-TCFA plaques (0.57 +/- 0.50% vs. 0.41 +/- 0.31%, P =
      0.08). Similar results were also obtained within 1000 MUm depth. Positive linear
      correlation was demonstrated between bright spot density and hsCRP level (r =
      0.45, P = 0.002). Using a novel algorithm, we demonstrated a significantly higher
      density of bright spots in the culprit lesions of patients presenting with ACS,
      particularly in case of plaque rupture, compared to those presenting with SAP.
      The density of bright spots also correlates with inflammatory status. These
      results suggest that the quantitative assessment of bright spot density may be
      useful in evaluating plaque vulnerability.

PMID- 26202159
TI  - Diagnostic accuracy of late iodine enhancement on cardiac computed tomography
      with a denoise filter for the evaluation of myocardial infarction.
AB  - We evaluated the image quality and diagnostic performance of late iodine
      enhancement (LIE) in dual-source computed tomography (DSCT) with low kilo-voltage
      peak (kVp) images and a denoise filter for the detection of acute myocardial
      infarction (AMI) in comparison with late gadolinium enhancement (LGE) magnetic
      resonance imaging (MRI). The Hospital Ethics Committee approved the study
      protocol. Before discharge, 19 patients who received percutaneous coronary
      intervention after AMI underwent DSCT and 1.5 T MRI. Immediately after coronary
      computed tomography (CT) angiography, contrast medium was administered at a slow
      injection rate. LIE-CT scans were acquired via dual-energy CT and reconstructed
      as 100-, 140-kVp, and mixed images. An iterative three-dimensional edge-preserved
      smoothing filter was applied to the 100-kVp images to obtain denoised 100-kVp
      images. The mixed, 140-kVp, 100-kVp, and denoised 100-kVp images were assessed
      using contrast-to-noise ratio (CNR), and their diagnostic performance in
      comparison with MRI and infarcted volumes were evaluated. Three hundred four
      segments of 19 patients were evaluated. Fifty-three segments showed LGE in MRI.
      The median CNR of the mixed, 140-, 100-kVp and denoised 100-kVp images was 3.49,
      1.21, 3.57, and 6.08, respectively. The median CNR was significantly higher in
      the denoised 100-kVp images than in the other three images (P < 0.05). The
      denoised 100-kVp images showed the highest diagnostic accuracy and sensitivity.
      The percentage of myocardium in the four CT image types was significantly
      correlated with the respective MRI findings. The use of a denoise filter with a
      low-kVp image can improve CNR, sensitivity, and accuracy in LIE-CT. 

PMID- 26202160
TI  - The recurrent chromosomal translocation t(12;18)(q14~15;q12~21) causes the fusion
      gene HMGA2-SETBP1 and HMGA2 expression in lipoma and osteochondrolipoma.
AB  - Lipomas are the most common soft tissue tumors in adults. They often carry
      chromosome aberrations involving 12q13~15 leading to rearrangements of the HMGA2
      gene in 12q14.3, with breakpoints occurring within or outside of the gene. Here,
      we present eleven lipomas and one osteochondrolipoma with a novel recurrent
      chromosome aberration, t(12;18)(q14~15;q12~21). Molecular studies on eight of the
      tumors showed that full-length HMGA2 transcript was expressed in three and a
      chimeric HMGA2 transcript in five of them. In three lipomas and in the
      osteochondrolipoma, exons 1-3 of HMGA2 were fused to a sequence of SETBP1 on
      18q12.3 or an intragenic sequence from 18q12.3 circa 10 kbp distal to SETBP1. In
      another lipoma, exons 1-4 of HMGA2 were fused to an intronic sequence of GRIP1
      which maps to chromosome band 12q14.3, distal to HMGA2. The ensuing HMGA2 fusion
      transcripts code for putative proteins which contain amino acid residues of HMGA2
      corresponding to exons 1-3 (or exons 1-4 in one case) followed by amino acid
      residues corresponding to the fused sequences. Thus, the pattern is similar to
      the rearrangements of HMGA2 found in other lipomas, i.e., disruption of the HMGA2
      locus leaves intact exons 1-3 which encode the AT-hooks domains and separates
      them from the 3'-terminal part of the gene. The fact that the examined
      osteochondrolipoma had a t(12;18) and a HMGA2-SETBP1 fusion identical to the
      findings in the much more common ordinary lipomas, underscores the close
      developmental relationship between the two tumor types. 

PMID- 26202161
TI  - Design and acceptance of Rheumates@Work, a combined internet-based and in person
      instruction model, an interactive, educational, and cognitive behavioral program
      for children with juvenile idiopathic arthritis.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease.
      Patients suffer daily discomforts such as pain, fatigue, stiffness, and mood
      disturbances. Their exercise capacity is decreased to a variable degree and
      physical activity levels may be impaired. To prevent long-term cardiovascular
      risks associated with JIA and medication, it is important to encourage physical
      activity. To achieve this we developed Rheumates@Work (R@W), a combined internet
      based and in person instruction model, an interactive, educational, and cognitive
      behavioral program. The aim of this study is twofold: to describe the theoretical
      background and design of R@W based on Pender's Health Promotion Model, and to
      assess its acceptance. METHODS: We enrolled 8 to 13-year-old JIA patients, from 3
      outpatients clinics in The Netherlands, in R@W. Inclusion criteria were a low
      disease activity (VAS physician <20 mm), comprehension of the Dutch language and
      absence of relevant co-morbidity. We assessed acceptance by measuring the
      participants' commitment to the program, the level of interaction on patient's
      initiative (f.e. mails send by the patient), technical aspects and satisfaction.
      Commitment was defined as the percentage of participants that completed the
      assignments and how much encouragement the participants needed for this.
      Satisfaction was measured with an anonymous questionnaire concerning f.e. time
      investment and perceived benefits. Costs were monitored. RESULTS: Of the 64
      patients we enrolled, 23 boys and 41 girls, 93.8 % completed the program.
      Participant-initiated interaction was seen in 10.7 %, 24.7 % send a mail because
      of technical problems. Eighty-two percent of the participants and 99 % of the
      parents liked the program, and 85 % of the participants indicated that they had
      learnt something, or quite a lot. Development costs of the program were low.
      CONCLUSION: The HPM is suitable for a behavioral intervention program such as
      R@W. Acceptance and satisfaction of R@W were high and the costs of the program
      were low. TRIAL REGISTRATION:  TRIAL NUMBER: ISRCTN92733069.

PMID- 26202162
TI  - Handling trial participants with missing outcome data when conducting a meta
      analysis: a systematic survey of proposed approaches.
AB  - BACKGROUND: When potentially associated with the likelihood of outcome, missing
      participant data represents a serious potential source of bias in randomized
      trials. Authors of systematic reviews frequently face this problem when
      conducting meta-analyses. The objective of this study is to conduct a systematic
      survey of the relevant literature to identify proposed approaches for how
      systematic review authors should handle missing participant data when conducting
      a meta-analysis. METHODS: We searched MEDLINE and the Cochrane Methodology
      register from inception to August 2014. We included papers that devoted at least
      two paragraphs to discuss a relevant approach for missing data. Five pairs of
      reviewers, working independently and in duplicate, selected relevant papers. One
      reviewer abstracted data from included papers and a second reviewer verified
      them. We summarized the results narratively. RESULTS: Of 9,138 identified
      citations, we included 11 eligible papers. Four proposed general approaches for
      handling dichotomous outcomes, and all recommended a complete case analysis as
      the primary analysis and additional sensitivity analyses using the following
      imputation methods: based on reasons for missingness (n = 3), relative to risk
      among followed up (n = 3), best-case scenario (n = 2), and worst-case scenario (n
      = 3). Three of these approaches suggested taking uncertainty into account. Two
      papers proposed general approaches for handling continuous outcomes, and both
      proposed a complete case analysis as the reference analysis and the following
      imputation methods as sensitivity analyses: based on reasons for missingness (n =
      2), based on the mean observed in the same trial or other trials (n = 1), and
      based on informative missingness differences in means (n = 1). The remaining
      eligible papers did not propose general approaches but addressed specific
      statistical issues. CONCLUSIONS: All proposed approaches for handling missing
      participant data recommend conducting a complete case analysis for the primary
      analysis and some form of sensitivity analysis to evaluate robustness of results.
      Although these approaches require further testing, they may guide review authors
      in addressing missing participant data.

PMID- 26202163
TI  - The number of discharge medications predicts thirty-day hospital readmission: a
      cohort study.
AB  - BACKGROUND: Hospital readmission occurs often and is difficult to predict.
      Polypharmacy has been identified as a potential risk factor for hospital
      readmission. However, the overall impact of the number of discharge medications
      on hospital readmission is still undefined. METHODS: To determine whether the
      number of discharge medications is predictive of thirty-day readmission using a
      retrospective cohort study design performed at Barnes-Jewish Hospital from
      January 15, 2013 to May 9, 2013. The primary outcome assessed was thirty-day
      hospital readmission. We also assessed potential predictors of thirty-day
      readmission to include the number of discharge medications. RESULTS: The final
      cohort had 5507 patients of which 1147 (20.8 %) were readmitted within thirty
      days of their hospital discharge date. The number of discharge medications was
      significantly greater for patients having a thirty-day readmission compared to
      those without a thirty-day readmission (7.2 +/- 4.1 medications [7.0 medications
      (4.0 medications, 10.0 medications)] versus 6.0 +/- 3.9 medications [6.0
      medications (3.0 medications, 9.0 medications)]; P < 0.001). There was a
      statistically significant association between increasing numbers of discharge
      medications and the prevalence of thirty-day hospital readmission (P < 0.001).
      Multiple logistic regression identified more than six discharge medications to be
      independently associated with thirty-day readmission (OR, 1.26; 95 % CI, 1.17
      1.36; P = 0.003). Other independent predictors of thirty-day readmission were:
      more than one emergency department visit in the previous six months, a minimum
      hemoglobin value less than or equal to 9 g/dL, presence of congestive heart
      failure, peripheral vascular disease, cirrhosis, and metastatic cancer. A risk
      score for thirty-day readmission derived from the logistic regression model had
      good predictive accuracy (AUROC = 0.661 [95 % CI, 0.643-0.679]). CONCLUSIONS: The
      number of discharge medications is associated with the prevalence of thirty-day
      hospital readmission. A risk score, that includes the number of discharge
      medications, accurately predicts patients at risk for thirty-day readmission. Our
      findings suggest that relatively simple and accessible parameters can identify
      patients at high risk for hospital readmission potentially distinguishing such
      individuals for interventions to minimize readmissions.

PMID- 26202165
TI  - Effect of different depths of anesthesia on postoperative cognitive function in
      laparoscopic patients: a randomized clinical trial.
AB  - OBJECTIVE: Postoperative cognitive dysfunction (POCD) is caused by many factors.
      This work was conducted to investigate the effect of different depths of
      anesthesia during combined intravenous-inhalational anesthesia on postoperative
      cognitive function in young and middle-aged laparoscopic patients. METHODS: A
      total of 192 patients scheduled for gynecologic laparoscopic operations were
      randomly divided into three groups. Anesthesia was maintained with inhalation of
      sevoflurane and infusion of remifentanil, which was adjusted to maintain
      bispectral index (BIS) at 30 < BIS <= 40 in Group I, 40 < BIS <= 50 in Group II
      and 50 < BIS <= 60 in Group III. The Mini-Mental State Examination (MMSE) and
      Trail-Making Test (TMT) were used to assess cognitive function on the day before
      anesthesia and the day after surgery. RESULTS: There were no significant
      differences in age, body mass index, educational level and surgery time. On the
      day before anesthesia, the average MMSE scores and TMT completion times in the
      three groups were not significantly different. On the day after surgery, Group II
      had a significantly higher average MMSE score (29.00 +/- 0.89) than Group I
      (28.36 +/- 1.42, p = 0.010) and Group III (28.45 +/- 1.27, p = 0.035) and lower
      TMT completion time (33.68 +/- 10.34) than Group I (39.45 +/- 13.99, p = 0.027)
      and Group III (39.50 +/- 12.50, p = 0.026). CONCLUSION: These results indicated
      that the depth of anesthesia, 40 < BIS <= 50, under combined intravenous
      inhalational anesthesia yielded milder influence on postoperative cognitive
      function in young and middle-aged laparoscopic patients.

PMID- 26202164
TI  - Patient experiences in retinal trials: a cross-sectional study.
AB  - BACKGROUND: Patient-centered care recognizes the obligation to understand and
      meet patient's expectations. An individual's satisfaction has been found to
      affect health-related decisions and treatment-related behaviours, which in turn
      affect medical compliance, follow-up, the success of treatment and the
      appropriate use of services. We studied the expectations, experiences and
      satisfaction of patients who participated in clinical trials for retinal diseases
      at the Sydney Eye Hospital. METHODS: The study was undertaken at the research
      clinic of the major public quaternary eye hospital in New South Wales, Australia.
      A 37-question survey was conducted on patients enrolled in or who had finished a
      clinical trial for macular disease in the 12 months preceding this study in
      November 2012. Patient satisfaction was assessed using close-ended, multiple
      choice questions. First, the decision making process for entering into the
      clinical trial was evaluated. Then the level of patient understanding and
      experience during the study was assessed. Finally, there was a series of
      questions to gauge the participants' perception of trial outcomes and overall
      impression gained from the experience. RESULTS: Eighty patients completed the
      questionnaire. Overall patient satisfaction was high with the majority of
      patients stating they would recommend participation in a retinal clinical trial
      (94 %) and participate in a subsequent trial (78 %). Most patients rated
      themselves as the most important factor in making the decision to join a trial.
      Patients felt well informed and expectations were generally felt to be met,
      however 14 % did not believe that they could withdraw from the study voluntarily.
      The most common reasons for trial participation were to contribute to medical
      science and to have improved treatment outcomes. CONCLUSIONS: We found that
      patients generally found participation in retinal clinical trials to be a
      positive experience. Factors contributing to dissatisfaction mainly related to
      inconvenience experienced by transportation and waiting times. We also found that
      patients felt well informed about the study, but some did not have a complete
      understanding of their rights, which had been communicated to them when they
      entered the study. There were both altruistic and self-motivated reasons behind
      patients' decisions to join a retinal trial.

PMID- 26202166
TI  - Recruitment strategies for British South Asians in 5 depression trials: A mixed
      method study.
AB  - BACKGROUND: In the United Kingdom, ethnic minority group's particularly British
      South Asian women have higher rates of depression than their white counterparts.
      Despite this they remain under represented in mental health trials. Whilst the US
      legislation mandates the inclusion of ethnic minorities into research, there are
      no similar initiatives in the UK. Barriers in recruiting these hard to reach
      ethnic groups are cited as major reasons behind this under representation. Once
      these barriers are encountered it becomes a challenge for the researchers to
      overcome them. As there is paucity of research in this specific area through this
      paper we want to share our strategies in recruiting British South Asians thus
      encouraging other researchers to consider ethnic minority inclusion into
      research. METHODS: Our published systematic review on the barriers to recruitment
      of ethnic minority participants into mental health research developed a typology
      of thirty three ethnic recruitment barriers described under five themes. We aimed
      to find strategies to overcome these barriers from five depression trials for
      British South Asians conducted by our research group. Firstly we extracted data
      on recruitment strategies from the published papers. Later researchers involved
      in these five trials formed a working group to add to these extracted strategies.
      Finally these strategies were matched to the individual barriers described in the
      typology. RESULTS: Multiple recruitment strategies were described by the
      researchers. These strategies were matched to all but two recruitment barriers
      related to psychopathology/substance misuse by the participants and paucity of
      healthcare related resources. Multiple strategies were found to be effective
      against each barrier and appropriate ones could be selected by the researchers
      after considering available resources at hand. CONCLUSIONS: Findings from this
      paper have implications for the design of recruitment strategies for hard to
      recruit ethnic minority groups to health care research. There is need for wider
      training and support of researchers to give them the skills to recruit these
      ethnic groups. Further development and evaluation of these strategies will lead
      to increased recruitment accruals.

PMID- 26202168
TI  - A comparison of plasma and prostate lycopene in response to typical servings of
      tomato soup, sauce or juice in men before prostatectomy.
AB  - Tomato product consumption and estimated lycopene intake are hypothesised to
      reduce the risk of prostate cancer. To define the impact of typical servings of
      commercially available tomato products on resultant plasma and prostate lycopene
      concentrations, men scheduled to undergo prostatectomy (n 33) were randomised
      either to a lycopene-restricted control group ( < 5 mg lycopene/d) or to a tomato
      soup (2-23/4 cups prepared/d), tomato sauce (142-198 g/d or 5-7 ounces/d) or
      vegetable juice (325-488 ml/d or 11-16.5 fluid ounces/d) intervention providing
      25-35 mg lycopene/d. Plasma and prostate carotenoid concentrations were measured
      by HPLC. Tomato soup, sauce and juice consumption significantly increased plasma
      lycopene concentration from 0.68 (sem 0.1) to 1.13 (sem 0.09) MUmol/l (66 %),
      0.48 (sem 0.09) to 0.82 (sem 0.12) MUmol/l (71 %) and 0.49 (sem 0.12) to 0.78
      (sem 0.1) MUmol/l (59 %), respectively, while the controls consuming the lycopene
      restricted diet showed a decline in plasma lycopene concentration from 0.55 (sem
      0.60) to 0.42 (sem 0.07) MUmol/l ( - 24 %). The end-of-study prostate lycopene
      concentration was 0.16 (sem 0.02) nmol/g in the controls, but was 3.5-, 3.6- and
      2.2-fold higher in tomato soup (P= 0.001), sauce (P= 0.001) and juice (P= 0.165)
      consumers, respectively. Prostate lycopene concentration was moderately
      correlated with post-intervention plasma lycopene concentrations (r 0.60, P
      =0.001), indicating that additional factors have an impact on tissue
      concentrations. While the primary geometric lycopene isomer in tomato products
      was all-trans (80-90 %), plasma and prostate isomers were 47 and 80 % cis,
      respectively, demonstrating a shift towards cis accumulation. Consumption of
      typical servings of processed tomato products results in differing plasma and
      prostate lycopene concentrations. Factors including meal composition and genetics
      deserve further evaluation to determine their impacts on lycopene absorption and
      biodistribution.

PMID- 26202167
TI  - Gene-based meta-analysis of genome-wide association study data identifies
      independent single-nucleotide polymorphisms in ANXA6 as being associated with
      systemic lupus erythematosus in Asian populations.
AB  - OBJECTIVE: Previous genome-wide association studies (GWAS), which were mainly
      based on single-variant analysis, have identified many systemic lupus
      erythematosus (SLE) susceptibility loci. However, the genetic architecture of
      this complex disease is far from being understood. The aim of this study was to
      investigate whether using a gene-based analysis may help to identify novel loci,
      by considering global evidence of association from a gene or a genomic region
      rather than focusing on evidence for individual variants. METHODS: Based on the
      results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we
      performed an in-depth gene-based analysis followed by replication in a total of
      4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic
      expression was measured by pyrosequencing. RESULTS: More than one-half of the
      reported SLE susceptibility loci showed evidence of independent effects, and this
      finding is important for understanding the mechanisms of association and
      explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility
      gene, with several single-nucleotide polymorphisms (SNPs) contributing
      independently to the association with disease. The risk allele of rs11960458
      correlated significantly with increased expression of ANXA6 in peripheral blood
      mononuclear cells from heterozygous healthy control subjects. Several other
      associated SNPs may also regulate ANXA6 expression, according to data obtained
      from public databases. Higher expression of ANXA6 in patients with SLE was also
      reported previously. CONCLUSION: Our study demonstrated the merit of using gene
      based analysis to identify novel susceptibility loci, especially those with
      independent effects, and also demonstrated the widespread presence of loci with
      independent effects in SLE susceptibility genes.

PMID- 26202169
TI  - Ectopic overexpression of the aldehyde dehydrogenase ALDH21 from Syntrichia
      caninervis in tobacco confers salt and drought stress tolerance.
AB  - Aldehyde dehydrogenases are important enzymes that play vital roles in mitigating
      oxidative/electrophilic stress when plants are exposed to environmental stress.
      An aldehyde dehydrogenase gene from Syntrichia caninervis, ScALDH21, was
      introduced into tobacco using Agrobacterium-mediated transformation to generate
      ScALDH21-overexpressing tobacco plants to investigate its effect on drought and
      salt resistance. Detached leaves from ScALDH21-overexpressing tobacco plants
      showed less water loss than those from nontransgenic plants. When subjected to
      drought and salt stress, transgenic plants displayed higher germination ratios,
      higher root lengths, greater fresh weight, higher proline accumulation, lower
      malondialdehyde (MDA) contents and stronger photosynthetic capacities, as well as
      higher activities of antioxidant enzymes, i.e., superoxide dismutase, catalase
      and peroxidase, compared with control plants. Therefore, ScALDH21 overexpression
      in transgenic tobacco plants can enhance drought and salt tolerance and can be
      used as a candidate gene for the molecular breeding of salt- and drought-tolerant
      plants. 

PMID- 26202170
TI  - Stochastic multiscale modelling of cortical bone elasticity based on high
      resolution imaging.
AB  - Accurate and reliable assessment of bone quality requires predictive methods
      which could probe bone microstructure and provide information on bone mechanical
      properties. Multiscale modelling and simulation represent a fast and powerful way
      to predict bone mechanical properties based on experimental information on bone
      microstructure as obtained through X-ray-based methods. However, technical
      limitations of experimental devices used to inspect bone microstructure may
      produce blurry data, especially in in vivo conditions. Uncertainties affecting
      the experimental data (input) may question the reliability of the results
      predicted by the model (output). Since input data are uncertain, deterministic
      approaches are limited and new modelling paradigms are required. In this paper, a
      novel stochastic multiscale model is developed to estimate the elastic properties
      of bone while taking into account uncertainties on bone composition. Effective
      elastic properties of cortical bone tissue were computed using a multiscale model
      based on continuum micromechanics. Volume fractions of bone components (collagen,
      mineral, and water) were considered as random variables whose probabilistic
      description was built using the maximum entropy principle. The relevance of this
      approach was proved by analysing a human bone sample taken from the inferior
      femoral neck. The sample was imaged using synchrotron radiation micro-computed
      tomography. 3-D distributions of Haversian porosity and tissue mineral density
      extracted from these images supplied the experimental information needed to build
      the stochastic models of the volume fractions. Thus, the stochastic multiscale
      model provided reliable statistical information (such as mean values and
      confidence intervals) on bone elastic properties at the tissue scale. Moreover,
      the existence of a simpler "nominal model", accounting for the main features of
      the stochastic model, was investigated. It was shown that such a model does
      exist, and its relevance was discussed. 

PMID- 26202172
TI  - Unprecedentedly high formic acid dehydrogenation activity on an iridium complex
      with an N,N'-diimine ligand in water.
AB  - Hydrogen production from the dehydrogenation of formic acid (FA) is promising.
      Most of the current catalysts for FA dehydrogenation are effective only in the
      presence of bases or additives. We report here newly developed iridium complexes
      containing conjugated N,N'-diimine ligands for FA dehydrogenation in water
      without the addition of bases or additives. A turnover frequency (TOF) of 487 500
      h(-1) with [Cp*Ir(L1)Cl]Cl (L1=2,2'-bi-2-imidazoline) at 90  degrees C and a
      turnover number (TON) of 2 400 000 with in situ prepared catalyst from [IrCp*Cl2
      ]2 and 2,2'-bi-1,4,5,6-tetrahydropyrimidine (L2) at 80  degrees C were obtained,
      the highest values reported for FA dehydrogenation to date. A mechanistic study
      reveals that the formation of [Ir-H] intermediate species is the rate-determining
      step in the catalytic cycle. 

PMID- 26202171
TI  - Morphologic Features and Clinical Impact of Arteritis Concurrent with Transplant
      Glomerulopathy.
AB  - Little is known about the morphology and clinical relevance of arteritis in renal
      allograft biopsies with transplant glomerulopathy. We retrospectively reviewed
      the morphologic findings and clinical course of 59 patients with cg, 16 of which
      featured concurrent arteritis (fibrosing intimal arteritis with luminal narrowing
      in 15, and acute intimal arteritis in 1 case). Fifteen out of the 16 cases with
      arteritis fulfilled the morphological diagnostic criteria for chronic active
      antibody-mediated rejection, and 11 cases with arteritis showed morphological
      evidence of concurrent, ongoing T-cell-mediated alloimmune response (acute T-cell
      mediated rejection in 5, borderline changes in 6 cases). Further, the Banff
      grades of interstitial inflammation in scarred and nonscarred cortex, total
      cortical inflammation, and arterial luminal narrowing were significantly higher
      in biopsies with arteritis. By immunohistochemistry, T-lymphocyte predominance
      over macrophages was found in the intimal infiltrates in 14 out of 16 cases, and
      cytotoxic T-lymphocytes were identified among intimal mononuclears in 10 cases.
      Patients with arteritis demonstrated a significantly shorter renal survival (7.5
      vs. 29 months). In conclusion, T-cell-mediated mechanisms could play a role in
      the development of arteritis concurrent with cg. However, this finding does not
      exclude the possibility that antibody-mediated rejection can also contribute to
      the evolution of the lesion. Importantly, the lesion carries negative prognostic
      value likely via severe arterial luminal narrowing. 

PMID- 26202173
TI  - How complement activation influences the development of chronic synovitis in a
      mouse model of rheumatoid arthritis.
AB  - OBJECTIVES: Chronic synovitis is the main characteristic of rheumatoid arthritis
      (RA), defined by the proliferation of synovial lining cells, an important source
      of chemokines and cytokines associated with inflammation. The aim of this study
      was to examine the influence of complement functional activity on the development
      of chronic synovitis. METHOD: The experiments were conducted in zymosan-induced
      arthritis (ZIA) provoked by intra-articular injection of 180 MUg zymosan. Mice
      were treated with 10 ng/g body weight (bw) cobra venom factor (CVF) on days -3
      and -2 or with 10 ng/g bw CVF on days 7, 12, and 17 of ZIA. The percentage of
      neutrophils (CD11b+Ly6G+), macrophages (F4/80), and complement 5 anaphylatoxin
      receptor (C5aR)-positive cells in the synovial fluid (SF) were determined by flow
      cytometry and the expression of C5aR and C3aR in the synovium was detected
      immunohistochemically. RESULTS: The induction of ZIA in the absence of complement
      activity strongly inhibited the development of synovitis. By contrast, complement
      activation during ZIA exacerbated chronic synovitis through an increase in
      macrophage infiltration, C5aR and C3aR expression in the joints, and C5aR
      expression on SF cells. Levels of C5a and soluble receptor activator of nuclear
      factor kappa B ligand (sRANKL) in the SF were elevated whereas neutrophil
      infiltration and levels of tumour necrosis factor (TNF)-alpha and interleukin
      (IL)-6 in the SF were unchanged. CONCLUSIONS: Our findings indicate an important
      role for functional complement activity in the maintenance of chronic synovitis
      in a model of RA. Antagonizing complement activation represents new possibilities
      for the amelioration of synovitis symptoms.

PMID- 26202174
TI  - Intercostal nerve transfer to the biceps motor branch in complete traumatic
      brachial plexus injuries.
AB  - The purpose of this report is to critically evaluate our results of two
      intercostal nerve transfers directly to the biceps motor branch in complete
      traumatic brachial plexus injuries. From January 2007 to November 2012, 19
      patients were submitted to this type of surgery, but only 15 of them had a follow
      up for >=2 years and were included in this report. The mean interval from trauma
      to surgery was 6.88 months (ranging from 3 to 9 months). Two intercostals nerves
      were dissected and transferred directly to the biceps motor branch. The mean
      follow-up was 38.06 months (ranging from 24 to 62 months). Ten patients (66.6%)
      recovered an elbow flexion strength >=M3. Four of them (26.66%) recovered a
      stronger elbow flexion >=M4. One patient (6.25%) recovered an M2 elbow flexion
      and four patients (26.66%) did not regain any movement. We concluded that two
      intercostal nerve transfers to the biceps motor branch is a procedure with
      moderate results regarding elbow flexion recovery, but it is still one of the few
      options available in complete brachial plexus injuries, especially in five roots
      avulsion scenario.

PMID- 26202175
TI  - Hyperthyroidism in 276 Children and Adolescents with Type 1 Diabetes from Germany
      and Austria.
AB  - BACKGROUND/AIMS: Little is known about the incidence and clinical consequences of
      hyperthyroidism in pediatric patients with type 1 diabetes mellitus (T1DM).
      METHODS: We analyzed the DPV database (Diabetes Prospective Follow-Up Registry)
      to investigate the rate of hyperthyroidism in pediatric T1DM patients, its impact
      on metabolic control, and potential associations with organ-specific
      autoantibodies. RESULTS: Hyperthyroidism was found in 276/60,456 patients (0.46%)
      and was associated with younger age, shorter diabetes duration, female sex, and
      reduced body mass index. Diabetic ketoacidosis (DKA) and hypoglycemia were more
      frequent in T1DM with comorbid hyperthyroidism, while long-term metabolic control
      (HbA1c) was similar in both groups. Absolute blood pressure and arterial
      hypertension rate were elevated in the hyperthyroid patients. Rates of
      microalbuminuria and diabetic retinopathy were not different. Thyroid-specific
      antibodies (thyroid peroxidase, thyroglobulin, thyroid receptor) were associated
      with hyperthyroidism. Thyroid volume and rates of cysts and nodules were higher,
      and echogenicity was decreased. CONCLUSION: Prevalence of hyperthyroidism is low
      in diabetic children with T1DM but increased compared to children <18 years
      without diabetes. Hyperthyroidism is primarily associated with acute diabetes
      complications (DKA and hypoglycemia) and affects blood pressure regulation. Long
      term metabolic control or insulin requirement were not different.

PMID- 26202176
TI  - Emergency Cerclage: Improvement of Outcomes by Standardization of Management.
AB  - INTRODUCTION: Cervical dilatation followed by prolapse and ballooning of
      membranes into the vagina at mid-gestation is a critical situation. The aim of
      this study was to describe the outcome of emergency cerclage in a tertiary
      referral center during a 10-year period (2001-2010) in which a defined selection
      of women and standard protocol were introduced. SUBJECTS AND METHODS: Thirty-nine
      cases of emergency cervical cerclage performed before 24 completed weeks were
      retrospectively reviewed. Data related to maternal history, diagnosis, procedure
      details, postoperative management and perinatal outcome were recorded. Maternal
      characteristics and perinatal outcomes are described. RESULTS: Gestational age at
      cerclage (mean +/- SD) was 22.1 +/- 2.0 weeks with 61% (24/39) of women
      presenting bulging membranes. Gestational age at delivery and cerclage-to
      delivery time (mean +/- SD) were 28.6 +/- 6.2 weeks and 49.1 +/- 36.5 days,
      respectively. Only 38.5% (15/39) of the whole group and 44.1% (15/34) of those
      who reached 24.0 weeks delivered beyond 28 weeks of gestational age. Neonatal
      survival before discharge was 82.4% (28/34). DISCUSSION: Perinatal outcomes after
      emergency cerclage are still poor with more than half of the cases delivering
      before 28 weeks. A standard protocol may help in the management of these rare
      cases.

PMID- 26202177
TI  - Resveratrol prevents doxorubicin-induced cardiotoxicity in H9c2 cells through the
      inhibition of endoplasmic reticulum stress and the activation of the Sirt1
      pathway.
AB  - Treatment with doxorubicin (DOX) is one of the major causes of chemotherapy
      induced cardiotoxicity and is therefore, the principal limiting factor in the
      effectiveness of chemotherapy for cancer patients. DOX-induced heart failure is
      thought to result from endoplasmic reticulum (ER) stress and cardiomyocyte
      apoptosis. Resveratrol (RV), a polyphenol antioxidant found in red wine, has been
      shown to play a cardioprotective role. The aim of the present study was to
      examine the effects of RV on DOX-induced cardiotoxicity in H9c2 cells. We
      hypothesized that RV would protect H9c2 cells against DOX-induced ER stress and
      subsequent cell death through the activation of the Sirt1 pathway. Our results
      demonstrated that the decrease observed in the viability of the H9c2 cells
      following exposure to DOX was accompanied by a significant increase in the
      expression of the ER stress-related proteins, glucose-regulated protein 78
      (GRP78) and C/EBP homologous protein (CHOP). However, we found that RV
      downregulated the expression of ER stress marker protein in the presence of DOX
      and restored the viability of the H9c2 cells. Exposure to RV or DOX alone only
      slightly increased the protein expression of Sirt1, whereas a significant
      increase in Sirt1 protein levels was observed in the cells treated with both RV
      and DOX. The Sirt1 inhibitor, nicotinamide (NIC), partially neutralized the
      effects of RV on the expression of Sirt1 in the DOX-treated cells and completely
      abolished the effects of RV on the expression of GRP78 and CHOP. The findings of
      our study suggest that RV protects H9c2 cells against DOX-induced ER stress
      through ER stabilization, and more specifically through the activation of the
      Sirt1 pathway, thereby leading to cardiac cell survival.

PMID- 26202178
TI  - The basophil activation test: a sensitive test in the diagnosis of allergic
      immediate hypersensitivity to pristinamycin.
AB  - Immediate hypersensitivity (IHS) reactions to macrolides and to macrolide-derived
      antibiotics like pristinamycin are uncommon. In this context, there is little
      data available to appreciate the true value of biological tools regarding the
      diagnosis of immediate allergy to pristinamycin. Here we assess the clinical
      usefulness of the basophil activation test (BAT) to differentiate allergic from
      nonallergic IHS to pristinamycin. Thirty-six patients were tested with skin tests
      as the gold standard and BAT. The BAT achieved a sensitivity of 76% and a
      specificity of 100%, implying an absence of false positive results. Multicenter
      studies remain to be performed to better define the sensitivity, specificity and
      interlaboratory variation of BAT in the diagnosis of allergy to pristinamycin and
      macrolides.

PMID- 26202180
TI  - Does chronic hypertension prevent cancer progression?

PMID- 26202179
TI  - Comparative effectiveness of sildenafil for pulmonary hypertension due to left
      heart disease with HFrEF.
AB  - There is no cure for pulmonary hypertension due to left heart disease (PH-LHD),
      but the rationale for using sildenafil to treat pulmonary arterial hypertension
      with heart failure with reduced ejection fraction (HFrEF) has been supported by
      short-term studies. We performed a meta-analysis to evaluate the effectiveness of
      sildenafil for PH-LHD with HFrEF. A systematic literature search of PubMed,
      EMBASE and the Cochrane Central Register of Controlled Trials was conducted from
      inception through October 2014 for randomized trials and for observational
      studies with control groups, evaluating the effectiveness of sildenafil to treat
      PH-LHD with HFrEF. Sildenafil therapy decreased pulmonary arterial systolic
      pressure both at the acute phase and at the 6-month follow-up (weighted mean
      difference (WMD): -6.03 mm Hg, P=0.02; WMD: -11.47 mm Hg, P<0.00001,
      respectively). Sildenafil was found to reduce mean pulmonary artery pressure
      (WMD: -3 mm Hg, P=0.0004) and pulmonary vascular resistance (WMD: -60.0 dynes cm(
      5), P=0.01) at the 3-month follow-up. Oxygen consumption at peak significantly
      increased to 3.66 ml min(-1) kg(-1) (P<0.00001), 3.36 ml min(-1) kg(-1)
      (P<0.00001) and 2.60 ml min(-1) kg(-1) (P=0.03) at 3, 6 and 12 months,
      respectively. There were significant reductions in ventilation to CO2 production
      slope of -2.00, -4.68 and -7.12 at 3, 6 and 12 months, respectively (P<0.00001).
      Sildenafil was superior to placebo regarding left ventricular ejection fraction
      at the 6-month follow-up (WMD: 4.35, P<0.00001), and it significantly improved
      quality of life. Sildenafil therapy could effectively improve pulmonary
      hemodynamics and cardiopulmonary exercise testing measurements of PH-LHD with
      HFrEF, regardless of acute or chronic treatment. 

PMID- 26202181
TI  - Importance of follow-up after delivery in women who experience hypertensive
      disorders during pregnancy.

PMID- 26202182
TI  - 5 f -shell correlation effects in dioxides of light actinides studied by O 1s x
      ray absorption and emission spectroscopies and first-principles calculations.
AB  - Soft x-ray emission and absorption spectroscopic data are reported for the O 1s
      region of a single crystal of UO2, a polycrystalline NpO2 sample, and a single
      crystal of PuO2. The experimental data are interpreted using first-principles
      correlated-electron calculations within the framework of the density functional
      theory with added Coulomb U interaction (DFT+U). A detailed analysis regarding
      the origin of different structures in the x-ray emission and x-ray absorption
      spectra is given and the effect of varying the intra-atomic Coulomb interaction-U
      for the 5 f electrons is investigated. Our data indicate that O 1s x-ray
      absorption and emission spectroscopies can, in combination with DFT+U
      calculations, successfully be used to study 5 f -shell Coulomb correlation
      effects in dioxides of light actinides. The values for the Coulomb U parameter in
      these dioxides are derived to be in the range of 4-5 eV.

PMID- 26202183
TI  - Effects of exercise on postexercise ventricular-arterial coupling and pulsatile
      efficiency in patients with systolic dysfunction.
AB  - BACKGROUND: A suboptimal ventricular-arterial (VA) interaction may have a
      prolonged depressing effect on the failing heart after functional reserves forced
      to their limits under stress conditions such as exercise. The continuation of
      excessive load in the postexercise period may be more important than the load
      during exercise, because the sum of postexercise periods generally exceeds
      exercise time itself. We sought that exercise-induced changes in postexercise VA
      coupling and pulsatile efficiency in patients with heart failure (HF). METHODS:
      Thirty consecutive HF with reduced ejection fraction (EF) and thirty age-, sex-
      and peak VO2 -matched subjects with preserved EF were enrolled. Pre- and
      postexercise echocardiographic and tonometric measurements were taken to
      calculate left ventricular and arterial elastances, arterial compliance and wave
      reflections, and steady and pulsatile power. RESULTS: VA coupling significantly
      deteriorated in HF group (from 1.50 +/- 0.47 to 2.00 +/- 0.75 mmHg/mL, P < 0.01),
      but control group maintained basal favourable coupling status after exercise
      (from 1.04 +/- 0.29 to 1.03 +/- 0.24 mmHg/mL, P = 0.77). Pulsatile percentage of
      total power significantly increased with exercise in HF group, whereas it showed
      a significant decrease in control group. The change in pulsatile power fraction
      was correlated with the change in augmentation pressure (r = 0.41, beta = 3.00, P
      < 0.01) and inversely correlated with the change in total arterial compliance (r
      = -0.29, beta = -8.52, P = 0.02). CONCLUSION: Our data indicate that exercise
      induced VA decoupling and pulsatile inefficiency extend into postexercise phase
      in patients with systolic dysfunction. The exact duration of these derangements
      requires further studies.

PMID- 26202184
TI  - Cyclical relationship between depressive symptoms and diabetes distress in people
      with Type 2 diabetes mellitus: results from the Montreal Evaluation of Diabetes
      Treatment Cohort Study.
AB  - AIMS: To determine if longitudinal cyclical relationships exist between
      depressive symptoms and diabetes distress in people with Type 2 diabetes
      mellitus. METHODS: Data were obtained from the Montreal Evaluation of Diabetes
      Treatment study, a cohort study of 1691 people with Type 2 diabetes mellitus.
      Depressive symptoms and diabetes distress, measured with the Patient Health
      Questionnaire and Diabetes Distress Scale, respectively, were assessed at
      baseline, 1 year and 2 years. A cross-lagged path model analysis with all
      autoregressive associations was used. Paths and indirect associations were
      examined. RESULTS: All paths in the model were significant. Depressive symptoms
      were positively associated with diabetes distress across consecutive time points
      and diabetes distress was positively associated with depressive symptoms across
      consecutive time points. The association between depressive symptoms at baseline
      and depressive symptoms at 2 years was mediated by both depressive symptoms and
      diabetes distress at 1 year. The association between diabetes distress at
      baseline and diabetes distress at 2 years was also mediated by both depressive
      symptoms and diabetes distress. CONCLUSIONS: Depressive symptoms and diabetes
      distress are cyclically related; results suggest that depressive symptoms
      influence diabetes distress, which, in turn, influences depressive symptoms.
      Although many studies focus on the differences between depressive symptoms and
      diabetes distress, the present study is the first to provide longitudinal
      evidence that these constructs are cyclically related.

PMID- 26202185
TI  - Glycemic and Cholesterol Control Versus Single-Goal Control in US Veterans with
      Newly Diagnosed Type 2 Diabetes: A Retrospective Observational Study.
AB  - INTRODUCTION: A majority of patients with diabetes do not have levels of glycated
      hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) under control,
      either individually or in combination. The objective was to assess the clinical
      benefits and patient characteristics associated with dual-goal achievement [HbA1c
      <7% (53 mmol/mol) and LDL-C <100 mg/dL] versus only LDL-C goal achievement in
      adults with newly diagnosed type 2 diabetes. METHODS: Newly diagnosed patients
      with >=2 measures of LDL-C and HbA1c were identified in the South Central
      Veterans Affairs Health Care Network (01/2004-06/2010). The index date was the
      first HbA1c assessment within 3 months of the first type 2 diabetes diagnosis.
      Multivariate Cox proportional hazards models were used to assess the association
      between time-varying goal achievement and post-index microvascular and
      cardiovascular complications. Patient characteristics associated with dual-goal
      achievement in the 7-12 months post-index were identified using a logistic
      regression. RESULTS: The sample included 16,829 patients. Compared with LDL-C
      goal achievement, dual-goal achievement was associated with lower risk of
      microvascular complications [hazard ratio (95% confidence interval): 0.69 (0.63,
      0.76)]. Other outcomes did not differ between those two groups. Characteristics
      associated with dual-goal achievement (44.2% of patients) include prior dual-goal
      achievement, older age, and use of lipid-lowering drugs. CONCLUSION: Dual-goal
      achievement in newly diagnosed type 2 diabetes is associated with a lower risk of
      microvascular complications versus only LDL-C goal achievement. Although dual
      goal achievement rates are suboptimal, early and regular intervention will
      increase its likelihood. FUNDING: Daiichi Sankyo, Inc., Parsippany, NJ, USA.

PMID- 26202186
TI  - Understanding the Molecular Mechanisms of Rifaximin in the Treatment of
      Gastrointestinal Disorders--A Focus on the Modulation of Host Tissue Function.
AB  - Rifaximin is a broad-spectrum oral antibiotic, exhibiting limited systemic
      absorption, that is used clinically to treat a variety of gastrointestinal
      disorders, including traveller's diarrhea, hepatic encephalopathy, irritable
      bowel syndrome, and the inflammatory bowel diseases. Rifaximin's antimicrobial
      properties, in the context of enteric infections, and its effects on the host's
      intestinal microbiota have been well characterized. More recently, it has been
      reported that rifaximin can modulate host tissue function through the activation
      of distinct molecular events. Within the gastrointestinal tract, rifaximin is a
      selective agonist of the pregnane X receptor (PXR), a nuclear receptor that
      regulates the expression of genes related to xenobiotic metabolism and drug
      detoxification. The PXR can also elicit immunomodulatory effects through its
      interaction with a variety of intracellular signaling cascades, including the
      nuclear factor kappa B and c-jun N-terminal kinase pathways. In this review, we
      will summarize the clinical uses of rifaximin and discuss its mechanism of action
      in relation to the modulation of the intestinal microbiota and the regulation of
      gastrointestinal host cell function, with a specific focus on PXR-dependent
      pathways. 

PMID- 26202187
TI  - Past, Present and Future of Antiepileptic Drug Therapy - Finding a Place for
      Heterocyclics.
AB  - Epilepsy is a serious brain condition characterized by recurring seizures. It
      affects millions of people across the globe. Much advancement in the past has
      improved the understanding of the underlying pathophysiology and risk factors for
      epilepsy. These advances have led to the development of both new terminologies
      and classification as well as treatment strategies for the disease. Despite the
      fact that various antiepileptic drugs have been developed in past decades, major
      part of affected population remains either resistant or refractory to the
      currently available therapy. Also, none of these anticonvulsant agents are devoid
      of serious side effect. Therefore, constant efforts are being made to develop
      antiepileptic drugs with improved efficacy and better pharmacokinetic and safety
      profile. The new structural classes which are being developed broadly amides,
      amino acids and a number of heterocyclic agents like oxadiazoles, benzimidazoles,
      benzothazoles, pyrazoles, indoles and benzothaizoles etc. These new compounds
      have potential for identification of novel targets and drug development. This
      review makes a note of these issues and describes recent developments in
      antiepileptic drug discovery. 

PMID- 26202188
TI  - Recent Advances in Synthetic Chemistry of Diabetic Research.
AB  - Diseases started even before the existence of human beings. Therefore, when the
      civilization began, the biggest threats for human were diseases. Man has made
      several sincere attempts for the search of new drugs in order to cure and control
      different diseases. Type 2 diabetes mellitus (T2DM) is a chronic metabolic
      disorder that accounts for about 85-95% of all diagnosed cases of diabetes. It is
      characterized by abnormalities in glucose homeostasis in many organs, and is
      associated with considerable morbidity and mortality. Extensive research has been
      carried out using rational drug design to identify and optimize new leads for
      molecular targets of T2DM, which include Heterocyclic compounds, metal complexes,
      H3 receptor antagonists, glucagon receptor antagonists and human incretin
      degrading enzyme dipeptidyl peptidase IV inhibitors. 

PMID- 26202189
TI  - Voltage-Gated Sodium Channels as Therapeutic Targets for Treatment of Painful
      Diabetic Neuropathy.
AB  - Painful diabetic neuropathy (PDN) is one of most common complication of diabetes,
      usually affecting 50% of diabetic patients and remains important cause of
      morbidity, mortality and deterioration of quality of life. PDN is well
      characterised by chronic hyperglycemia, alterations in expression and kinetics of
      voltage-gated sodium channels (VGSCs) and neuro-inflammation which together may
      result into sensorimotor deficits in peripheral nervous system. Peripheral
      nociceptive neurons express variety of sodium channel isoforms particularly
      Nav1.3, Nav1.7, Nav1.8 and Nav1.9, each play a key role in physiology of
      nociception by undergoing respective dynamic changes in expression and voltage
      dependent gating properties. Thus, they are critical determinants of sensory
      neuronal excitability and associated neuropathic pain signal. Recent preclinical
      and clinical trial research has shed light on VGSCs as most compelling target in
      the treatment of PDN, a development that may open up new therapeutic approaches
      involving subtype selective sodium channel blockers to boost clinical efficacy,
      cost effectiveness, better tolerability and targeted treatment. In this review,
      we have summarized structure and functions of VGSCs and their involvement in the
      pathophysiology of neuropathic pain along with the current status of
      pharmacological interventions targeted at VGSCs in the treatment of diabetic
      neuropathy. 

PMID- 26202190
TI  - Detrimental Effects of Hyperglycemia in Acute Coronary Syndromes: from
      Pathophysiological Mechanisms to Therapeutic Strategies.
AB  - Hyperglycemia recognized during hospitalization for acute coronary syndromes
      (ACS) is common. It is a powerful predictor of worse prognosis in patients both
      with and without previously known diabetes mellitus. Hyperglycemia during ACS is
      caused by an inflammatory and adrenergic response to ischemic stress, when
      catecholamines are released and glycogenolysis induced. The link between
      hyperglycemia and prognosis in ACS patients is multi-factorial. Hyperglycemia
      exerts detrimental effects on left ventricular and platelet function and it also
      activates other systemic pathological processes that contribute to cellular and
      tissue injury such as increasing oxidative stress and worsening endothelial
      function. Glucose management strategies in ACS may improve outcome in patients
      with hyperglycemia, by reducing inflammatory and clotting mediators, by improving
      endothelial function and fibrinolysis and by reducing infarct size. Most of
      available oral anti-diabetic drugs are contraindicated for the increased risk of
      hypoglycemia. Thus, insulin is the preferred agent for glycemic control in ACS
      and conversion from intravenous to subcutaneous therapy commonly occurs when the
      critical acute phase of ACS resolves. Pharmacodynamics of insulin allows it to be
      adaptable to the changing physiology of the ACS patient, is easily titrated and
      has no dosage threshold. Nevertheless, findings concerning the effect on ACS
      related mortality of the control of glucose levels by intravenous infusion of
      insulin have been conflicting and intervention trials are needed to optimize the
      definition of hyperglycemia and to establish appropriate modalities and goals of
      glucose lowering treatment. In particular, the clinical benefit of an aggressive
      treatment with insulin is yet unproved. 

PMID- 26202191
TI  - The Role of Intestinal Microbiota in Graft versus Host Disease.
AB  - Graft versus host disease (GVHD) remains a major life threatening complication
      and one of the primary barriers to successful allogeneic hematopoietic stem cell
      transplantation, limiting its application in nonmalignant conditions.
      Immunosuppression is used for prevention and treatment of GVHD, dampening the
      graft versus leukemia effect. Intestinal bacteria play a major role in
      inflammation and augmenting the GVHD cytokine response. Early studies in murine
      models showed that manipulating the presence of intestinal flora or counteracting
      its byproducts could limit GVHD. Thus multiple clinical trials targeting gut
      decontamination were conducted, with the aims of modulating inflammation and
      protecting against GVHD, with mixed results. More recent work has improved our
      understanding of the role of intestinal microbiota in the maintenance of innate
      immunity, mucosal integrity and limiting inflammation. This review offers a
      summary of this data, with a discussion of potential therapeutic interventions
      manipulating the intestinal microbiota. 

PMID- 26202193
TI  - Rifaximin: The Revolutionary Antibiotic Approach for Irritable Bowel Syndrome.
AB  - A large number of clinical studies using breath testing and a smaller number of
      studies using quantitative cultures of the upper small intestine established a
      link between irritable bowel syndrome (IBS) and small intestinal bacterial
      overgrowth (SIBO). A series of 12 studies both prospective and retrospective in
      design in a population of patients with SIBO without IBS showed that the non
      absorbable antibiotic rifaximin can eradicate SIBO as proved through decrease of
      the exhaled hydrogen and methane in breath tests. The efficacy of rifaximin was
      superior over the comparator treatment in most of these studies. Based on these
      findings, short course rifaximin was tested in various concentrations in eight
      open-label trials in patients with IBS and proven SIBO by breath test. Similar
      efficacy of rifaximin was shown in SIBO eradication; this was accompanied by
      improvement of the global score for IBS symptoms. Finally, five double-blind
      randomized clinical trials were conducted in patients with IBS; four were placebo
      controlled. The larger trials were TARGET 1 and TARGET 2 studies testing
      rifaximin at a regimen of 550 mg tid for 14 days. All trials showed a significant
      superiority of rifaximin over comparator for the improvement of global symptoms
      of IBS and bloating. Although the aforementioned results render rifaximin a
      revolutionary therapeutic approach for IBS, several concerns on induction of
      antimicrobial resistant flora remain.

PMID- 26202192
TI  - Rifaximin: An Antibiotic with Important Biologic Effects.
AB  - Rifaximin is a poorly absorbed rifamycin drug with unique pharmacokinetic
      properties: bile solubility making it highly active against pathogenic and non
      pathogenic bacterial flora in the bile-rich small bowel and low water solubility
      making it active only against highly susceptible bacteria, primarily anaerobes,
      in the aqueous colon. The drug has anti-inflammatory gut mucosal stabilization
      properties that are important to its sustained effects in non-infectious
      diseases. Rifaximin is used chronically or recurrently for hepatic encephalopathy
      and diarrhea-predominant irritable bowel syndrome. Monitoring of long-term use of
      rifaximin for development of resistance and then determining whether developed
      resistance is associated with reduced efficacy are needed. Studies of changes of
      intestinal flora during therapy and the health implications of these changes are
      also needed. 

PMID- 26202194
TI  - Role of Rifaximin in Inflammatory Bowel Disease Treatment.
AB  - Inflammatory bowel diseases are characterised by an altered composition of the
      intestinal microbiota, which may contribute to their development and maintenance
      in susceptible hosts. The involvement of bacteria in the inflammation has
      provided the rationale for a therapeutic manipulation of the gut flora through
      the use of antibiotics. However, the role of antibiotics has not been clearly
      demonstrated and their long-term employment is often restricted by an elevated
      number of adverse events. The use of rifaximin, which is characterised by an
      excellent safety profile thanks to its negligible intestinal absorption, appears
      to have some promise. Study results suggest that rifaximin could be useful in
      Crohn's disease, and a new gastroresistant formulation (rifaximin-extended
      intestinal release) has recently shown its efficacy in patients with moderate
      Crohn's disease. Less consistent data support the use of rifaximin in ulcerative
      colitis and in pouchitis, although the results of some studies have been
      encouraging. Further large controlled trials are warranted to confirm the role of
      rifaximin in inflammatory bowel disease treatment.

PMID- 26202195
TI  - Central and Mucosal Immunities are Modified by Non Adsorbable Antibiotic
      Treatment in Uncomplicated Diverticular Disease.
AB  - We review our experience on Rifaximin in uncomplicated diverticular disease. Our
      data show that a 2 week treatment induces modifications in the immune system:
      local mucosal lymphocytes with TLR-4 were increased. In the peripheral blood
      CD103 cells, which increased before treatment, returned to normal values after
      Rifaximin. 

PMID- 26202196
TI  - Promise and Pragmatism in Clinical Microbiome Research.
AB  - The evolution of human microbiome research has lead to a systems biology approach
      that encompasses multidisciplinary investigations. The implementation of next
      generation sequencing technologies has allowed researchers to study unculturable
      organisms, discover novel ones, and provide insights into the role of the human
      microbiome in health and disease. When these approaches are applied to large
      scale longitudinal studies designed to interrogate the association of the
      microbiome with specific clinical outcomes, the development of new therapeutics
      and diagnostics intended to modulate or detect changes in microbiome composition
      to improve human health are born. We are just starting to unravel the role of the
      microbiome in a wide-variety of diseases, and while some of it appears to be
      related to causation and provide opportunities for intervention, a good dose of
      pragmatism is warranted as the field is still in its infancy. 

PMID- 26202197
TI  - Creatine and the Liver: Metabolism and Possible Interactions.
AB  - The process of creatine synthesis occurs in two steps, catalyzed by L
      arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N
      methyltransferase (GAMT), which take place mainly in kidney and liver,
      respectively. This molecule plays an important energy/pH buffer function in
      tissues, and to guarantee the maintenance of its total body pool, the lost
      creatine must be replaced from diet or de novo synthesis. Creatine administration
      is known to decrease the consumption of Sadenosyl methionine and also reduce the
      homocysteine production in liver, diminishing fat accumulation and resulting in
      beneficial effects in fatty liver and non-alcoholic liver disease. Different
      studies have shown that creatine supplementation could supply brain energy,
      presenting neuroprotective effects against the encephalopathy induced by
      hyperammonemia in acute liver failure. Creatine is also taken by many athletes
      for its ergogenic properties. However, little is known about the adverse effects
      of creatine supplementation, which are barely described in the literature, with
      reports of mainly hypothetical effects arising from a small number of scientific
      publications. Antioxidant effects have been found in several studies, although
      one of the theories regarding the potential for toxicity from creatine
      supplementation is that it can increase oxidative stress and potentially form
      carcinogenic compounds. 

PMID- 26202198
TI  - Effects of Creatine in Skeletal Muscle Cells and in Myoblasts Differentiating
      Under Normal or Oxidatively Stressing Conditions.
AB  - Creatine (Cr) - along with the Cr kinase (CK) system - plays a fundamental role
      in muscle biochemistry and physiology not limited to its ergogenic role. Indeed,
      Cr has been shown to exert pleiotropic effects, which promote protein accretion,
      muscle-specific protein synthesis, growth in cultured myogenic cells and favour
      the myogenic process either in normal or stressing conditions. This review
      focuses on the effects of Cr supplementation on cellular and mitochondrial
      biochemistry and function in the course of skeletal muscle differentiation,
      either in normal or oxidatively stressing conditions, and on the ensuing
      nutraceutical/therapeutic perspectives. 

PMID- 26202200
TI  - The Effects of Creatine Supplementation and Physical Exercise on Traumatic Brain
      Injury.
AB  - Traumatic brain injury (TBI) is a devastating disease frequently followed by
      significant behavioral disabilities and long-term medical complications that
      include a wide range of behavioral and emotional problems. TBI is characterized
      by a combination of immediate mechanical dysfunction of brain tissue and
      secondary damage developed over a longer period of time following the injury. The
      early inflammatory response after tissue injury can be triggered by several
      factors such as extravasated blood products and reactive oxygen species (ROS). It
      is important to note that energy generation and mitochondrial function are
      closely related to and interconnected with delayed secondary manifestations of
      brain injury, including early neuromotor dysfunction, cognitive impairment and
      post-traumatic epilepsy (PTE). Given the extent of post-traumatic changes in
      neuronal function and the possibility of amplifying secondary cascades, different
      therapies designed to minimize damage and retain/restore cellular function after
      TBI are currently being studied. In this context, the present review covers the
      preclinical and clinical literature investigating the role of inflammation and
      free radicals in secondary damage generated by several models of TBI.
      Furthermore, the present review aims to discuss the role of creatine, a guanidine
      compound popularly used as a performance-enhancing supplement for high-intensity
      athletic performance, in secondary damage induced by TBI. In this narrative
      review, we also discuss the beneficial effect of exercise performed in animal
      models of TBI and how the results from animal studies can be applied to clinical
      settings. 

PMID- 26202199
TI  - Augmentation of Creatine in the Heart.
AB  - Creatine is a principle component of the creatine kinase (CK) phosphagen system
      common to all vertebrates. It is found in excitable cells, such as
      cardiomyocytes, where it plays an important role in the buffering and transport
      of chemical energy to ensure that supply meets the dynamic demands of the heart.
      Multiple components of the CK system, including intracellular creatine levels,
      are reduced in heart failure, while ischaemia and hypoxia represent acute crises
      of energy provision. Elevation of myocardial creatine levels has therefore been
      suggested as potentially beneficial, however, achieving this goal is not trivial.
      This mini-review outlines the evidence in support of creatine elevation and
      critically examines the pharmacological approaches that are currently available.
      In particular, dietary creatine-supplementation does not sufficiently elevate
      creatine levels in the heart due to subsequent down-regulation of the plasma
      membrane creatine transporter (CrT). Attempts to increase passive diffusion and
      bypass the CrT, e.g. via creatine esters, have yet to be tested in the heart.
      However, studies in mice with genetic overexpression of the CrT demonstrate proof
      of-principle that elevated creatine protects the heart from ischaemia-reperfusion
      injury. This suggests activation of the CrT as a major unmet pharmacological
      target. However, translation of this finding to the clinic will require a greater
      understanding of CrT regulation in health and disease and the development of
      small molecule activators. 

PMID- 26202202
TI  - Progress in Small Molecule and Biologic Therapeutics Targeting Ghrelin Signaling.
AB  - Ghrelin is a circulating peptide hormone involved in regulation of a wide array
      of physiological processes. As an endogenous ligand for growth hormone
      secretagogue receptor (GHSR1a), ghrelin is responsible for signaling involved in
      energy homeostasis, including appetite stimulation, glucose metabolism, insulin
      signaling, and adiposity. Ghrelin has also been implicated in modulation of
      several neurological processes. Dysregulation of ghrelin signaling is implicated
      in diseases related to these pathways, including obesity, type II diabetes, and
      regulation of appetite and body weight in patients with Prader-Willi syndrome.
      Multiple steps in the ghrelin signaling pathway are available for targeting in
      the development of therapeutics for these diseases. Agonists and antagonists of
      GHS-R1a have been widely studied and have shown varying levels of effectiveness
      within ghrelin-related physiological pathways. Agents targeting ghrelin directly,
      either through depletion of ghrelin levels in circulation or inhibitors of
      ghrelin O-acyltransferase whose action is required for ghrelin to become
      biologically active, are receiving increasing attention as potential therapeutic
      options. We discuss the approaches utilized to target ghrelin signaling and
      highlight the current challenges toward developing small-molecule agents as
      potential therapeutics for ghrelin-related diseases. 

PMID- 26202203
TI  - Posttranslational Regulation of O(6)-Methylguanine-DNA Methyltransferase (MGMT)
      and New Opportunities for Treatment of Brain Cancers.
AB  - O(6)-Methylguanine-DNA-methyltransferase (MGMT) is an antimutagenic DNA repair
      protein highly expressed in human brain tumors. Because MGMT repairs the
      mutagenic, carcinogenic and cytotoxic O(6)-alkylguanine adducts, including those
      generated by the clinically used anticancer alkylating agents, it has emerged as
      a central and rational target for overcoming tumor resistance to alkylating
      agents. Although the pseudosubstrates for MGMT [O(6)-benzylguanine, O(6)-(4-
      bromothenyl)guanine] have gained attention as powerful and clinically-relevant
      inhibitors, bone marrow suppression due to excessive alkylation damage has
      diminished this strategy. Our laboratory has been working on various
      posttranslational modifications of MGMT that affect its protein stability, DNA
      repair activity and response to oxidative stress. While these modifications
      greatly impact the physiological regulation of MGMT, they also highlight the
      opportunities for inactivating DNA repair and new drug discovery in this specific
      area. This review briefly describes the newer aspects of MGMT posttranslational
      regulation by ubiquitination, sumoylation and glutathionylation and reveals how
      the reactivity of the active site Cys145 can be exploited for potent inhibition
      and depletion of MGMT by thiol-reacting drugs such as the disulfiram and various
      dithiocarbamate derivatives. The possible repurposing of these nontoxic and safe
      drugs for improved therapy of pediatric and adult brain tumors is discussed. 

PMID- 26202201
TI  - Advances in Drug Discovery and Development for Pediatric Tuberculosis.
AB  - Pediatric tuberculosis is an underappreciated global epidemic estimated to
      afflict around half a million children worldwide. This problem has historically
      been overlooked, due in part to their low social status and the difficulty in
      diagnosis of tuberculosis in children. Children are more susceptible to
      tuberculosis infection and disease progression, including rapid dissemination
      into extrapulmonary infection sites. Treatment of pediatric tuberculosis
      infections has been traditionally built around agents used to treat the adult
      disease, but the disease pathology, drug pharmacokinetics and the safety window
      in children differs from the adult disease. This produces additional concerns for
      drug discovery and development of new agents. This review examines: (i) the
      safety concerns for current front and second line agents used to treat complex
      drug resistant infections and how this knowledge can be used to identify,
      prioritize and dose agents that may be better tolerated in pediatric populations;
      and (ii) the chemistry and suitability of new drugs in the clinical development
      pipeline for tuberculosis for the treatment of pediatric infections indicating
      several new agents may offer significant improvements for the treatment of multi
      drug resistant tuberculosis in children. 

PMID- 26202205
TI  - Drug Discovery for Paediatric Chagas Disease.
AB  - Chagas disease is caused by the parasite Trypanosoma cruzi and is regularly found
      among particular people living in Central and South America. Paediatric Chagas
      disease occurs in 1-10% of infants of infected mothers. The major important point
      considered in the treatment of congenital Chagas disease focuses on killing the
      parasite in acute infection and managing signs and symptoms in later stages.
      Nowadays, two drugs benznidazole and nifurtimox are currently available in the
      market for the treatment of paediatric Chagas disease.

PMID- 26202206
TI  - Path-programmable water droplet manipulations on an adhesion controlled
      superhydrophobic surface.
AB  - Here, we developed a novel and facile method to control the local water adhesion
      force of a thin and stretchable superhydrophobic polydimethylsiloxane (PDMS)
      substrate with micro-pillar arrays that allows the individual manipulation of
      droplet motions including moving, merging and mixing. When a vacuum pressure was
      applied below the PDMS substrate, a local dimple structure was formed and the
      water adhesion force of structure was significantly changed owing to the
      dynamically varied pillar density. With the help of the lowered water adhesion
      force and the slope angle of the formed dimple structure, the motion of
      individual water droplets could be precisely controlled, which facilitated the
      creation of a droplet-based microfluidic platform capable of a programmable
      manipulation of droplets. We showed that the platform could be used in newer and
      emerging microfluidic operations such as surface-enhanced Raman spectroscopy with
      extremely high sensing capability (10(-15) M) and in vitro small interfering RNA
      transfection with enhanced transfection efficiency of ~80%. 

PMID- 26202207
TI  - Safety and efficacy of abciximab in older adults undergoing percutaneous coronary
      intervention.
AB  - BACKGROUND: As a result of increased cost and bleeding concerns, older patients
      receive abciximab during percutaneous coronary intervention (PCI) less often than
      younger patients. OBJECTIVE: The aim of this was to evaluate the safety and
      efficacy of abciximab in older adults undergoing PCI. DESIGN: Retrospective,
      observational single centre cohort study. METHODS: The British Cardiovascular
      Intervention Society (BCIS) database was used to establish the impact of
      abciximab in people with advanced age (>= 75 years) on in-hospital bleeding and
      ischaemic events and all-cause mortality in 5727 consecutive patients undergoing
      PCI between January 2008 and June 2014. RESULTS: Older patients represented 23%
      of the study population (n = 1298). Abciximab was used in 198 (15%) older
      patients and 970 (22%) younger patients (p < 0.001). Unadjusted bleeding and
      mortality rates were 1.2% and 5.6%, respectively, vs. 0.4% and 1.7% in younger
      patients (p = 0.001 and p < 0.001 respectively). On multivariate analysis older
      subjects were at higher risk of bleeding [odds ratio (OR) 2.76, 95% confidence
      interval (CI) 1.26-6.04, p = 0.011] and had higher in-hospital mortality (OR
      2.36, 95% CI 1.48-3.74, p < 0.001). The use of abciximab in older patients was
      not significantly associated with excess bleeding (adjusted OR 1.86, 95% CI 0.58
      5.93, p = 0.3), ischaemic outcomes (adjusted OR, 95% CI, p = 0.12) or in-hospital
      mortality (adjusted OR, 95% CI, p = 0.11). Older patients having primary PCI had
      higher risk of bleeding irrespective of abciximab use (adjusted p = 0.042).
      CONCLUSION: Abciximab may not be associated with excess bleeding complications in
      older patients compared with younger individuals and may be safe to use in older
      people if indicated.

PMID- 26202204
TI  - Progress in Small Molecule Therapeutics for the Treatment of Retinoblastoma.
AB  - While mortality is low for intraocular retinoblastoma patients in the developed
      world who receive aggressive multimodal therapy, partial or full loss of vision
      occurs in approximately 50% of patients with advanced bilateral retinoblastoma.
      Therapies that preserve vision and reduce late effects are needed. Because
      clinical trials for retinoblastoma are difficult due to the young age of the
      patient population and relative rarity of the disease, robust preclinical testing
      of new therapies is critical. The last decade has seen advances towards
      identifying new therapies including the development of animal models of
      retinoblastoma for preclinical testing, progress in local drug delivery to reach
      intraocular targets, and improved understanding of the underlying biological
      mechanisms that give rise to retinoblastoma. This review discusses advances in
      these areas, with a focus on discovery and development of small molecules for the
      treatment of retinoblastoma, including novel targeted therapeutics such as
      inhibitors of the MDMX-p53 interaction (nutlin-3a), histone deacetylase (HDAC)
      inhibitors, and spleen tyrosine kinase (SYK) inhibitors. 

PMID- 26202208
TI  - Digestibility of gluten proteins is reduced by baking and enhanced by starch
      digestion.
AB  - SCOPE: Resistance of proteins to gastrointestinal digestion may play a role in
      determining immune-mediated adverse reactions to foods. However, digestion
      studies have largely been restricted to purified proteins and the impact of food
      processing and food matrices on protein digestibility is poorly understood.
      METHODS AND RESULTS: Digestibility of a total gliadin fraction (TGF), flour (cv
      Hereward), and bread was assessed using in vitro batch digestion with simulated
      oral, gastric, and duodenal phases. Protein digestion was monitored by SDS-PAGE
      and immunoblotting using monoclonal antibodies specific for celiac-toxic
      sequences (QQSF, QPFP) and starch digestion by measuring undigested starch.
      Whereas the TGF was rapidly digested during the gastric phase the gluten proteins
      in bread were virtually undigested and digested rapidly during the duodenal phase
      only if amylase was included. Duodenal starch digestion was also slower in the
      absence of duodenal proteases. CONCLUSION: The baking process reduces the
      digestibility of wheat gluten proteins, including those containing sequences
      active in celiac disease. Starch digestion affects the extent of protein
      digestion, probably because of gluten-starch complex formation during baking.
      Digestion studies using purified protein fractions alone are therefore not
      predictive of digestion in complex food matrices.

PMID- 26202209
TI  - Thymoquinone Ameliorates Acute Renal Failure in Gentamicin-Treated Adult Male
      Rats.
AB  - BACKGROUND: Gentamicin (GEN) is considered as a main aminoglycoside antibiotic
      medicine. The top therapeutic side effect of GEN is nephrotoxicity. The current
      research was proposed to determine the protective effect of thymoquinone (TQ) on
      GEN-induced acute renal failure (ARF). METHODS: The rats were divided into 6
      groups: sham group, control group, GEN-treated group and the TQ-treated groups.
      At the end of the research period, the serum blood urea nitrogen (BUN) and
      creatinine (Cr) were measured. The kidneys were then removed for evaluating
      malondialdehyde (MDA), reduced glutathione (GSH), interleukins IL-6, IL-10, IL-18
      and IL-1beta, tumor necrosis factor alpha (TNF-alpha), superoxide dismutase (SOD)
      and glutathione peroxidase (GPx) levels. RESULTS: GEN induced a raise in the
      levels of serum Cr, BUN and also the levels of MDA, IL-6, IL-18, IL-1beta and TNF
      alpha with decease in GSH, SOD, GPx and IL-10 in the kidney (p < 0.05). The data
      illustrated that the significant elevation in the levels of serum Cr, BUN, MDA,
      IL-6, IL-18, IL-1beta, TNF-alpha and also the reduction of GSH, SOD, SOD, GPx, IL
      10 in the kidney were ameliorated in the TQ-treated groups versus the untreated
      group, in a dose-dependent manner (p < 0.05). CONCLUSION: The present
      investigation proposes that TQ may be ameliorated ARF through modulation of the
      oxidative stress and inflammatory responses.

PMID- 26202210
TI  - Organochlorine compounds in Purple Heron eggs (Ardea purpurea) nesting in sites
      located around a chlor-alkali plant (Ebro River).
AB  - Eggs of Purple Heron (Ardea purpurea) were collected from three sampled sites
      inside the Ebro River basin in years 2006 and 2007. These sites were located
      besides (Flix), upstream (Aiguabarreig) and downstream (Delta) a chlor-alkali
      plant. Organochlorine compounds (OCs) such as dichlorodiphenyltrichloroethanes
      (DDTs), polychlorobiphenyls (PCBs), polychlorostyrenes (PCSs), hexachlorobenzene
      (HCB), pentachlorobenzene (PeCB) and hexachlorocyclohexanes (HCHs) were analysed
      to assess what are the accumulation patterns of these compounds in aquatic
      migratory birds breeding in the area of influence of the emissions from this
      industrial installation. Comparison of the egg concentrations between the three
      sites show higher concentrations of compounds manufactured in the past in the
      factory (PCBs, p,p'-DDT) or by-products of OC synthesis (HCB, PeCB and PCSs) in
      Flix than in Aiguabarreig reflecting a clear influence from the emissions of the
      chlor-alkali plant. The eggs collected in the Ebro Delta showed higher
      concentrations of total DDTs (mainly p,p'-DDE) than in the reference site
      (Aiguabarreig) which could reflect past applications of this insecticide in the
      area for agriculture. In contrast, HCHs were found in higher concentrations in
      the Delta and Aiguabarreig than in the Flix Reservoir. These compounds have been
      used as insecticides in agriculture and were not manufactured in the chlor-alkali
      plant. The present results show that despite Purple Herons are migratory birds,
      the food web transfer of OCs during the breeding season is sufficient for the
      accumulation of these compounds in the eggs, leading to statistically significant
      concentration differences between sites. These differences are consistent with
      the emissions of these pollutants from industrial or agricultural sources to the
      aquatic environments. Some of the p,p'-DDE concentrations observed in the area
      nearby the chlor-alkali plant are above the threshold effects for reproductive
      impairment. 

PMID- 26202211
TI  - Aggregating factors of the change process in the treatment of anorexia nervosa.
AB  - PURPOSE: We aimed to reduce the large body of factors which may be associated
      with the change process in treatments for Anorexia Nervosa (AN) into a clinically
      and scientifically useful number of higher-rank dimensions. In addition, we
      examined the associations between the identified factors and eating disorder
      psychopathology and body mass index (BMI) in exploratory analyses. METHODS:
      Within a naturalistic multicenter study we administered the Change Process
      Questionnaire (CPQ-AN) to inpatients with AN upon admission. The factorial
      structure of the CPQ-AN was explored via factor analysis. Multiple regression
      analyses were performed to examine the associations with BMI and eating disorder
      symptomatology (EDI-2). RESULTS: In total 233 female inpatients with AN (mean
      BMI=14.9 kg/m(2), SD=1.7) participated. The factor analysis yielded four latent
      factors: basic need satisfaction, AN-specific cognitions and behavior, emotional
      involvement and commitment to treatment, and alliance and treatment confidence.
      Furthermore, greater basic need satisfaction and less AN-specific cognitions and
      behavior predicted lower EDI-2 scores. Higher alliance and treatment confidence
      were associated with higher BMI as well as a lower EDI-2 score. CONCLUSION: The
      associations between the newly derived dimensions and BMI and AN-psychopathology
      provide evidence to support the clinical relevance of the identified change
      process dimensions. Future investigations could provide further insights to
      deepen our understanding of the change process in AN.

PMID- 26202212
TI  - Revealing the Macromolecular Targets of Fragment-Like Natural Products.
AB  - Fragment-like natural products were identified as ligand-efficient chemical
      matter for hit-to-lead development and chemical-probe discovery. Relying on a
      computational method using a topological pharmacophore descriptor and a drug
      database, several macromolecular targets from distinct protein families were
      expeditiously retrieved for structurally unrelated chemotypes. The selected
      fragments feature structural dissimilarity to the reference compounds and
      suitable target affinity, and they offer opportunities for chemical optimization.
      Experimental confirmation of hitherto unknown macromolecular targets for the
      selected molecules corroborate the usefulness of the computational approach and
      suggests broad applicability to chemical biology and molecular medicine. 

PMID- 26202213
TI  - Reducing intraoperative red blood cell unit wastage in a large academic medical
      center.
AB  - BACKGROUND: The wastage of red blood cell (RBC) units within the operative
      setting results in significant direct costs to health care organizations.
      Previous education-based efforts to reduce wastage were unsuccessful at our
      institution. We hypothesized that a quality and process improvement approach
      would result in sustained reductions in intraoperative RBC wastage in a large
      academic medical center. STUDY DESIGN AND METHODS: Utilizing a failure mode and
      effects analysis supplemented with time and temperature data, key drivers of
      perioperative RBC wastage were identified and targeted for process improvement.
      RESULTS: Multiple contributing factors, including improper storage and transport
      and lack of accurate, locally relevant RBC wastage event data were identified as
      significant contributors to ongoing intraoperative RBC unit wastage. Testing and
      implementation of improvements to the process of transport and storage of RBC
      units occurred in liver transplant and adult cardiac surgical areas due to their
      history of disproportionately high RBC wastage rates. Process interventions
      targeting local drivers of RBC wastage resulted in a significant reduction in RBC
      wastage (p < 0.0001; adjusted odds ratio, 0.24; 95% confidence interval, 0.15
      0.39), despite an increase in operative case volume over the period of the study.
      Studied process interventions were then introduced incrementally in the remainder
      of the perioperative areas. CONCLUSIONS: These results show that a
      multidisciplinary team focused on the process of blood product ordering,
      transport, and storage was able to significantly reduce operative RBC wastage and
      its associated costs using quality and process improvement methods.

PMID- 26202214
TI  - Age >=80 Years Is Not a Contraindication for Intra-Arterial Therapy after
      Ischemic Stroke.
AB  - BACKGROUND: Clinical trials confirmed the safety and efficacy of intra-arterial
      therapy (IAT) in the management of ischemic stroke. At a community hospital, we
      compared outcomes in patients aged >=80 and patients in the age range 55-79 years
      receiving IAT following ischemic stroke. METHODS: Data were retrospectively
      abstracted for ischemic stroke patients >=55 years treated with IAT at an urban
      comprehensive stroke center between 2010 and 2013. Baseline demographics,
      incidence of symptomatic intracranial hemorrhage (sICH), in-hospital mortality,
      discharge modified Rankin scale (mRS) score (favorable <=2) and improvement in
      National Institutes of Health Stroke Scale Score (NIHSS; decreased score at
      discharge) were compared between patients in the age range 55-79 and patients
      >=80 years. Data were analyzed using univariate analyses and multivariate
      logistic regression. RESULTS: IAT was performed in 239 patients with ischemic
      stroke; 63 (26.4%) were >=80 years. When compared to patients aged 55-79, the
      elderly patients were more often female and non-smokers, with a history of atrial
      fibrillation. No differences were observed in those >=80 years compared to
      patients in the age range 55-79 years for sICH (10 vs. 5%, p = 0.23), mortality
      (24 vs. 18%, p = 0.28), favorable discharge mRS score (13 vs. 19%, p = 0.27), or
      improvement in NIHSS (83 vs. 92%, p = 0.10). The nonsignificant association of
      age with the outcomes persisted after adjusting for covariates and when analyzing
      the subset of patients who received IAT only. CONCLUSIONS: These findings suggest
      that in a cohort not subject to the criteria of a clinical trial, age >=80 years
      should not be a contraindication to IAT.

PMID- 26202215
TI  - MiR-873 regulates ERalpha transcriptional activity and tamoxifen resistance via
      targeting CDK3 in breast cancer cells.

PMID- 26202216
TI  - Highly sensitive transient absorption imaging of graphene and graphene oxide in
      living cells and circulating blood.
AB  - We report a transient absorption (TA) imaging method for fast visualization and
      quantitative layer analysis of graphene and GO. Forward and backward imaging of
      graphene on various substrates under ambient condition was imaged with a speed of
      2 MUs per pixel. The TA intensity linearly increased with the layer number of
      graphene. Real-time TA imaging of GO in vitro with capability of quantitative
      analysis of intracellular concentration and ex vivo in circulating blood were
      demonstrated. These results suggest that TA microscopy is a valid tool for the
      study of graphene based materials. 

PMID- 26202217
TI  - Knowledge transfer via classification rules using functional mapping for
      integrative modeling of gene expression data.
AB  - BACKGROUND: Most 'transcriptomic' data from microarrays are generated from small
      sample sizes compared to the large number of measured biomarkers, making it very
      difficult to build accurate and generalizable disease state classification
      models. Integrating information from different, but related, 'transcriptomic'
      data may help build better classification models. However, most proposed methods
      for integrative analysis of 'transcriptomic' data cannot incorporate domain
      knowledge, which can improve model performance. To this end, we have developed a
      methodology that leverages transfer rule learning and functional modules, which
      we call TRL-FM, to capture and abstract domain knowledge in the form of
      classification rules to facilitate integrative modeling of multiple gene
      expression data. TRL-FM is an extension of the transfer rule learner (TRL) that
      we developed previously. The goal of this study was to test our hypothesis that
      "an integrative model obtained via the TRL-FM approach outperforms traditional
      models based on single gene expression data sources". RESULTS: To evaluate the
      feasibility of the TRL-FM framework, we compared the area under the ROC curve
      (AUC) of models developed with TRL-FM and other traditional methods, using 21
      microarray datasets generated from three studies on brain cancer, prostate
      cancer, and lung disease, respectively. The results show that TRL-FM
      statistically significantly outperforms TRL as well as traditional models based
      on single source data. In addition, TRL-FM performed better than other
      integrative models driven by meta-analysis and cross-platform data merging.
      CONCLUSIONS: The capability of utilizing transferred abstract knowledge derived
      from source data using feature mapping enables the TRL-FM framework to mimic the
      human process of learning and adaptation when performing related tasks. The novel
      TRL-FM methodology for integrative modeling for multiple 'transcriptomic'
      datasets is able to intelligently incorporate domain knowledge that traditional
      methods might disregard, to boost predictive power and generalization
      performance. In this study, TRL-FM's abstraction of knowledge is achieved in the
      form of functional modules, but the overall framework is generalizable in that
      different approaches of acquiring abstract knowledge can be integrated into this
      framework.

PMID- 26202218
TI  - Identification and characterisation of alternative transcriptional variants of
      PDGFRL in two lines of commercial poultry.
AB  - The platelet-derived growth factor (PDGF) family of genes and their receptors are
      involved in angiogenesis and steroid hormone production. A putative member of the
      family, platelet-derived growth factor receptor-like (PDGFRL), has been
      implicated in steroid-based feedback mechanisms within the chicken reproductive
      system. Three potential variants of PDGFRL were identified in the chicken,
      supported by in silico prediction and EST sequencing. The three potential
      transcripts have been further verified and the 5' terminal regions sequenced in
      this research. The sum of expression of all three transcripts in broiler breeders
      (the parents of broiler chickens) has been shown to be consistent with total
      expression of the gene. However, cumulative expression of the three transcripts
      in a range of tissues in egg layers was significantly short of total expression,
      indicating the existence of potential additional variants. Two additional
      variants were subsequently identified in egg layer cerebellum tissue and the 5'
      terminal regions sequenced. Sequence analysis of the three initial variants
      suggests that only one variant, which was the most abundant in broiler breeders
      and the majority of egg layer tissues, had a functional signal peptide. Although
      5' RACE identified two additional transcripts in egg layers, the most likely
      protein translations indicated that these variants possessed no functional signal
      peptide, suggesting that, if they have a function, it is not a traditional one. 

PMID- 26202219
TI  - MicroRNA dysregulation in rhabdomyosarcoma: a new player enters the game.
AB  - Rhabdomyosarcoma (RMS) is the most common of the soft tissue sarcomas with
      resultant high morbidity, frequently occuring in paediatric patients and young
      adults. While the molecular basis of RMS has received considerable attention,
      exact mechanisms underlying its development and metastasis remain unclear.
      MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that
      negatively regulate gene expression via translational inhibition or mRNA
      degradation. Deregulated expression of miRNA has been implicated in initiation,
      progression, and metastasis of RMS. miRNAs have emerged as key regulators of
      several physiological and pathophysiological processes and have opened new
      avenues for diagnosis and treatment of RMS. This review summarizes deregulation
      and functional roles of miRNAs in RMS and their potential applications for
      diagnosis, prognosis and treatment of this malignancy. As a rapidly evolving
      field in basic and translational medicine, it is hopeful that miRNA research will
      ultimately improve management of RMS. 

PMID- 26202220
TI  - Triggered Ca2+ influx is required for extended synaptotagmin 1-induced ER-plasma
      membrane tethering.
AB  - The extended synaptotagmins (E-Syts) are ER proteins that act as Ca(2+)-regulated
      tethers between the ER and the plasma membrane (PM) and have a putative role in
      lipid transport between the two membranes. Ca(2+) regulation of their tethering
      function, as well as the interplay of their different domains in such function,
      remains poorly understood. By exposing semi-intact cells to buffers of variable
      Ca(2+) concentrations, we found that binding of E-Syt1 to the PI(4,5)P2-rich PM
      critically requires its C2C and C2E domains and that the EC50 of such binding is
      in the low micromolar Ca(2+) range. Accordingly, E-Syt1 accumulation at ER-PM
      contact sites occurred only upon experimental manipulations known to achieve
      these levels of Ca(2+) via its influx from the extracellular medium, such as
      store-operated Ca(2+) entry in fibroblasts and membrane depolarization in beta
      cells. We also show that in spite of their very different physiological
      functions, membrane tethering by E-Syt1 (ER to PM) and by synaptotagmin
      (secretory vesicles to PM) undergo a similar regulation by plasma membrane lipids
      and cytosolic Ca(2+). 

PMID- 26202221
TI  - A NOVEL SUPPORT DEVICE FOR HEAD IMMOBILIZATION DURING RADIATION THERAPY THAT IS
      APPLICABLE TO BOTH CATS AND DOGS.
AB  - Repeatable head immobilization is important for minimizing positioning error
      during radiation therapy for veterinary patients with head neoplasms. The purpose
      of this retrospective cross-sectional study was to describe a novel technique for
      head immobilization (Device II) and compare this technique with a previously
      described technique (Device I). Device II provided additional support by
      incorporating three teeth (vs. two teeth with Device I). Between 2011 and 2013,
      both devices were applied in clinically affected cats (Device I, n = 17; Device
      II, n = 11) and dogs (Device I, n = 85; Device II, n = 22) of various breeds and
      sizes. The following data were recorded for each included patient: variability in
      the angle of the skull (roll, yaw, and pitch), coordinates of the isocenter, and
      distance from the reference mark to the tumor. Devices I and II differed for
      skull angle variability during the treatment of dogs (roll, P = 0.0007; yaw, P =
      0.0018; pitch, P = 0.0384) and for yaw of during the treatment of cats (P <
      0.0001). In each case, Device II was superior to Device I. The distance from the
      reference mark to the center of the tumor was significantly decreased for Device
      II vs. Device I (dogs, P < 0.0001; cats, P = 0.0002). Device II also provided
      more accurate coordinates for the isocenter. Authors recommend the use of, Device
      II for future clinical patients. 

PMID- 26202222
TI  - UTP activates small-conductance Ca2+-activated K+ channels in murine detrusor
      PDGFRalpha+ cells.
AB  - Purines induce transient contraction and prolonged relaxation of detrusor
      muscles. Transient contraction is likely due to activation of inward currents in
      smooth muscle cells, and prolonged relaxation may be due to activation of small
      conductance Ca(2+)-activated K(+) (SK) channels via P2Y1 receptors expressed by
      detrusor PDGF receptor (PDGFR)alpha(+) cells. We investigated whether other
      subtypes of P2Y receptors are involved in the activation of SK channels in
      PDGFRalpha(+) cells of detrusor muscles. Quantitative analysis of transcripts
      revealed that P2ry2, P2ry4, and P2ry14 are expressed in PDGFRalpha(+) cells of
      P2ry1-deficient/enhanced green fluorescent protein (P2ry1(-/-)/eGFP) mice at
      similar levels as in wild-type mice. UTP, a P2Y2/P2Y4 agonist, activated large
      outward currents in detrusor PDGFRalpha(+) cells. SK channel blockers and an
      inhibitor of phospholipase C completely abolished currents activated by UTP. In
      contrast, UTP activated nonselective cation currents in smooth muscle cells.
      Under current-clamp (current = 0), UTP induced significant hyperpolarization of
      PDGFRalpha(+) cells. MRS2500, a selective P2Y1 antagonist, did not affect UTP
      activated outward currents in PDGFRalpha(+) cells from wild-type mice, and
      activation of outward currents by UTP was retained in P2ry1(-/-)/eGFP mice. As a
      negative control, we tested the effect of MRS2693, a selective P2Y6 agonist. This
      compound did not activate outward currents in PDGFRalpha(+) cells, and currents
      activated by UTP were unaffected by MRS2578, a selective P2Y6 antagonist. The
      nonselective P2Y receptor blocker suramin inhibited UTP-activated outward
      currents in PDGFRalpha(+) cells. Our data demonstrate that P2Y2 and/or P2Y4
      receptors function, in addition to P2Y1 receptors, in activating SK currents in
      PDGFRalpha(+) cells and possibly in mediating purinergic relaxation responses in
      detrusor muscles. 

PMID- 26202223
TI  - Nonsteroidal anti-inflammatory drugs alter vasa recta diameter via pericytes.
AB  - We have previously shown that vasa recta pericytes are known to dilate vasa recta
      capillaries in the presence of PGE2 and contract vasa recta capillaries when
      endogenous production of PGE2 is inhibited by the nonselective nonsteroidal anti
      inflammatory drug (NSAID) indomethacin. In the present study, we used a live rat
      kidney slice model to build on these initial observations and provide novel data
      that demonstrate that nonselective, cyclooxygenase-1-selective, and
      cyclooxygenase -2-selective NSAIDs act via medullary pericytes to elicit a
      reduction of vasa recta diameter. Real-time images of in situ vasa recta were
      recorded, and vasa recta diameters at pericyte and nonpericyte sites were
      measured offline. PGE2 and epoprostenol (a prostacyclin analog) evoked dilation
      of vasa recta specifically at pericyte sites, and PGE2 significantly attenuated
      pericyte-mediated constriction of vasa recta evoked by both endothelin-1 and ANG
      II. NSAIDs (indomethacin > SC-560 > celecoxib > meloxicam) evoked significantly
      greater constriction of vasa recta capillaries at pericyte sites than at
      nonpericyte sites, and indomethacin significantly attenuated the pericyte
      mediated vasodilation of vasa recta evoked by PGE2, epoprostenol, bradykinin, and
      S-nitroso-N-acetyl-l-penicillamine. Moreover, a reduction in PGE2 was measured
      using an enzyme immune assay after superfusion of kidney slices with
      indomethacin. In addition, immunohistochemical techniques were used to
      demonstrate the population of EP receptors in the medulla. Collectively, these
      data demonstrate that pericytes are sensitive to changes in PGE2 concentration
      and may serve as the primary mechanism underlying NSAID-associated renal injury
      and/or further compound-associated tubular damage.

PMID- 26202225
TI  - Education and Imaging. Hepatobiliary and Pancreatic: Spontaneous bilioma
      secondary to ampullary cancer: a rare presentation.

PMID- 26202224
TI  - Renin expression in developing zebrafish is associated with angiogenesis and
      requires the Notch pathway and endothelium.
AB  - Although renin is a critical regulatory enzyme of the cardiovascular system, its
      roles in organogenesis and the establishment of cardiovascular homeostasis remain
      unclear. Mammalian renin-expressing cells are widespread in embryonic kidneys but
      are highly restricted, specialized endocrine cells in adults. With a functional
      pronephros, embryonic zebrafish are ideal for delineating the developmental
      functions of renin-expressing cells and the mechanisms governing renin
      transcription. Larval zebrafish renin expression originates in the mural cells of
      the juxtaglomerular anterior mesenteric artery and subsequently at extrarenal
      sites. The role of renin was determined by assessing responses to renin
      angiotensin system blockade, salinity variation, and renal perfusion ablation.
      Renin expression did not respond to renal flow ablation but was modulated by
      inhibition of angiotensin-converting enzyme and altered salinity. Our data in
      larval fish are consistent with conservation of renin's physiological functions.
      Using transgenic renin reporter fish, with mindbomb and cloche mutants, we show
      that Notch signaling and the endothelium are essential for developmental renin
      expression. After inhibition of angiogenesis, renin-expressing cells precede
      angiogenic sprouts. Arising from separate lineages, but relying on mutual
      interplay with endothelial cells, renin-expressing cells are among the earliest
      mural cells observed in larval fish, performing both endocrine and paracrine
      functions. 

PMID- 26202227
TI  - Type I Interferon Released by Myeloid Dendritic Cells Reversibly Impairs
      Cytomegalovirus Replication by Inhibiting Immediate Early Gene Expression.
AB  - Cytomegalovirus (CMV) is a ubiquitous beta-herpesvirus whose reactivation from
      latency is a major cause of morbidity and mortality in immunocompromised hosts.
      Mouse CMV (MCMV) is a well-established model virus to study virus-host
      interactions. We showed in this study that the CD8-independent antiviral function
      of myeloid dendritic cells (mDC) is biologically relevant for the inhibition of
      MCMV replication in vivo and in vitro. In vivo ablation of CD11c(+) DC resulted
      in higher viral titers and increased susceptibility to MCMV infection in the
      first 3 days postinfection. We developed in vitro coculture systems in which we
      cocultivated MCMV-infected endothelial cells or fibroblasts with T cell subsets
      and/or dendritic cells. While CD8 T cells failed to control MCMV replication,
      bone marrow-derived mDC reduced viral titers by a factor of up to 10,000. Contact
      of mDC with the infected endothelial cells was crucial for their antiviral
      activity. Soluble factors secreted by the mDC blocked MCMV replication at the
      level of immediate early (IE) gene expression, yet the viral lytic cycle
      reinitiated once the mDC were removed from the cells. On the other hand, the mDC
      did not impair MCMV replication in cells deficient for the interferon (IFN)
      alpha/beta receptor (IFNAR), arguing that type I interferons were critical for
      viral control by mDC. In light of our recent observation that type I IFN is
      sufficient for the induction of latency immediately upon infection, our results
      imply that IFN secreted by mDC may play an important role in the establishment of
      CMV latency. IMPORTANCE: Numerous studies have focused on the infection of DC
      with cytomegaloviruses and on the establishment of latency within them. However,
      almost all of these studies have relied on the infection of DC monocultures in
      vitro, whereas DC are just one among many cell types present in an infection site
      in vivo. To mimic this aspect of the in vivo situation, we cocultured DC with
      infected endothelial cells or fibroblasts. Our data suggest that direct contact
      with virus-infected endothelial cells activates CD11c(+) DC, which leads to
      reversible suppression of MCMV replication at the level of IE gene expression by
      a mechanism that depends on type I IFN. The effect matches the formal definition
      of viral latency. Therefore, our data argue that the interplay of dendritic cells
      and infected neighboring cells might play an important role in the establishment
      of viral latency.

PMID- 26202228
TI  - A Higher Frequency of NKG2A+ than of NKG2A- NK Cells Responds to Autologous HIV
      Infected CD4 Cells irrespective of Whether or Not They Coexpress KIR3DL1.
AB  - Epidemiological and functional studies implicate NK cells in HIV control.
      However, there is little information available on which NK cell populations, as
      defined by the inhibitory NK cell receptors (iNKRs) they express, respond to
      autologous HIV-infected CD4(+) (iCD4) T cells. NK cells acquire antiviral
      functions through education, which requires signals received from iNKRs, such as
      NKG2A and KIR3DL1 (here, 3DL1), engaging their ligands. NKG2A interacts with HLA
      E, and 3DL1 interacts with HLA-A/B antigens expressing the Bw4 epitope. HIV
      infected cells downregulate HLA-A/B, which should interrupt negative signaling
      through 3DL1, leading to NK cell activation, provided there is sufficient
      engagement of activating NKRs. We examined the functionality of NK cells
      expressing or not NKG2A and 3DL1 stimulated by HLA-null and autologous iCD4
      cells. Flow cytometry was used to gate on each NKG2A(+)/NKG2A(-) 3DL1(+)/3DL1(-)
      (NKG2A(+/-) 3DL1(+/-)) population and to measure the frequency of all possible
      combinations of CD107a expression and gamma interferon (IFN-gamma) and CCL4
      secretion. The highest frequency of functional NK cells responding to HLA-null
      cell stimulation was the NKG2A(+) 3DL1(+) NK cell population. The highest
      frequencies of functional NK cells responding to autologous iCD4 cells were those
      expressing NKG2A; coexpression of 3DL1 did not further modulate responsiveness.
      This was the case for the functional subsets characterized by the sum of all
      functions tested (total responsiveness), as well as by the trifunctional
      CD107a(+) IFN-gamma(+) CCL4(+), CD107a(+) IFN-gamma(+), total CD107a(+), and
      total IFN-gamma(+) functional subsets. These results indicate that the NKG2A
      receptor has a role in NK cell-mediated anti-HIV responses. IMPORTANCE: HIV
      infected CD4 (iCD4) cells activate NK cells, which then control HIV replication.
      However, little is known regarding which NK cell populations iCD4 cells stimulate
      to develop antiviral activity. Here, we examine the frequency of NK cell
      populations, defined by the presence/absence of the NK cell receptors (NKRs)
      NKG2A and 3DL1, that respond to iCD4 cells. NKG2A and 3DL1 are involved in
      priming NK cells for antiviral functions upon encountering virus-infected cells.
      A higher frequency of NKG2A(+) than NKG2A(-) NK cells responded to iCD4 cells by
      developing antiviral functions such as CD107a expression, which correlates with
      NK cell killing, and secretion of gamma interferon and CCL4. Coexpression of 3DL1
      on the NKG2A(+) and NKG2A(-) NK cells did not modulate responses to iCD4 cells.
      Understanding the mechanisms underlying the interaction of NK cells with iCD4
      cells that lead to HIV control may contribute to developing strategies that
      harness NK cells for preventing or controlling HIV infection.

PMID- 26202229
TI  - Brain Invasion by Mouse Hepatitis Virus Depends on Impairment of Tight Junctions
      and Beta Interferon Production in Brain Microvascular Endothelial Cells.
AB  - Coronaviruses (CoVs) have shown neuroinvasive properties in humans and animals
      secondary to replication in peripheral organs, but the mechanism of neuroinvasion
      is unknown. The major aim of our work was to evaluate the ability of CoVs to
      enter the central nervous system (CNS) through the blood-brain barrier (BBB).
      Using the highly hepatotropic mouse hepatitis virus type 3 (MHV3), its attenuated
      variant, 51.6-MHV3, which shows low tropism for endothelial cells, and the weakly
      hepatotropic MHV-A59 strain from the murine coronavirus group, we investigated
      the virus-induced dysfunctions of BBB in vivo and in brain microvascular
      endothelial cells (BMECs) in vitro. We report here a MHV strain-specific ability
      to cross the BBB during acute infection according to their virulence for liver.
      Brain invasion was observed only in MHV3-infected mice and correlated with
      enhanced BBB permeability associated with decreased expression of zona occludens
      protein 1 (ZO-1), VE-cadherin, and occludin, but not claudin-5, in the brain or
      in cultured BMECs. BBB breakdown in MHV3 infection was not related to production
      of barrier-dysregulating inflammatory cytokines or chemokines by infected BMECs
      but rather to a downregulation of barrier protective beta interferon (IFN-beta)
      production. Our findings highlight the importance of IFN-beta production by
      infected BMECs in preserving BBB function and preventing access of blood-borne
      infectious viruses to the brain. IMPORTANCE: Coronaviruses (CoVs) infect several
      mammals, including humans, and are associated with respiratory, gastrointestinal,
      and/or neurological diseases. There is some evidence that suggest that human
      respiratory CoVs may show neuroinvasive properties. Indeed, the severe acute
      respiratory syndrome coronavirus (SARS-CoV), causing severe acute respiratory
      syndrome, and the CoVs OC43 and 229E were found in the brains of SARS patients
      and multiple sclerosis patients, respectively. These findings suggest that
      hematogenously spread CoVs may gain access to the CNS at the BBB level. Herein we
      report for the first time that CoVs exhibit the ability to cross the BBB
      according to strain virulence. BBB invasion by CoVs correlates with virus-induced
      disruption of tight junctions on BMECs, leading to BBB dysfunction and enhanced
      permeability. We provide evidence that production of IFN-beta by BMECs during CoV
      infection may prevent BBB breakdown and brain viral invasion.

PMID- 26202230
TI  - Temporal Characterization of Marburg Virus Angola Infection following Aerosol
      Challenge in Rhesus Macaques.
AB  - Marburg virus (MARV) infection is a lethal hemorrhagic fever for which no
      licensed vaccines or therapeutics are available. Development of appropriate
      medical countermeasures requires a thorough understanding of the interaction
      between the host and the pathogen and the resulting disease course. In this
      study, 15 rhesus macaques were sequentially sacrificed following aerosol exposure
      to the MARV variant Angola, with longitudinal changes in physiology, immunology,
      and histopathology used to assess disease progression. Immunohistochemical
      evidence of infection and resulting histopathological changes were identified as
      early as day 3 postexposure (p.e.). The appearance of fever in infected animals
      coincided with the detection of serum viremia and plasma viral genomes on day 4
      p.e. High (>10(7) PFU/ml) viral loads were detected in all major organs (lung,
      liver, spleen, kidney, brain, etc.) beginning day 6 p.e. Clinical pathology
      findings included coagulopathy, leukocytosis, and profound liver destruction as
      indicated by elevated liver transaminases, azotemia, and hypoalbuminemia. Altered
      cytokine expression in response to infection included early increases in Th2
      cytokines such as interleukin 10 (IL-10) and IL-5 and late-stage increases in Th1
      cytokines such as IL-2, IL-15, and granulocyte-macrophage colony-stimulating
      factor (GM-CSF). This study provides a longitudinal examination of clinical
      disease of aerosol MARV Angola infection in the rhesus macaque model. IMPORTANCE:
      In this study, we carefully analyzed the timeline of Marburg virus infection in
      nonhuman primates in order to provide a well-characterized model of disease
      progression following aerosol exposure.

PMID- 26202231
TI  - Going Viral with Fluorescent Proteins.
AB  - Many longstanding questions about dynamics of virus-cell interactions can be
      answered by combining fluorescence imaging techniques with fluorescent protein
      (FP) tagging strategies. Successfully creating a FP fusion with a cellular or
      viral protein of interest first requires selecting the appropriate FP. However,
      while viral architecture and cellular localization often dictate the suitability
      of a FP, a FP's chemical and physical properties must also be considered. Here,
      we discuss the challenges of and offer suggestions for identifying the optimal
      FPs for studying the cell biology of viruses. 

PMID- 26202233
TI  - The Cellular Factor NXP2/MORC3 Is a Positive Regulator of Influenza Virus
      Multiplication.
AB  - Transcription and replication of influenza A virus are carried out in the nuclei
      of infected cells in the context of viral ribonucleoproteins (RNPs). The viral
      polymerase responsible for these processes is a protein complex composed of the
      PB1, PB2, and PA proteins. We previously identified a set of polymerase
      associated cellular proteins by proteomic analysis of polymerase-containing
      intracellular complexes expressed and purified from human cells. Here we
      characterize the role of NXP2/MORC3 in the infection cycle. NXP2/MORC3 is a
      member of the Microrchidia (MORC) family that is associated with the nuclear
      matrix and has RNA-binding activity. Influenza virus infection led to a slight
      increase in NXP2/MORC3 expression and its partial relocalization to the
      cytoplasm. Coimmunoprecipitation and immunofluorescence experiments indicated an
      association of NXP2/MORC3 with the viral polymerase and RNPs during infection.
      Downregulation of NXP2/MORC3 by use of two independent short hairpin RNAs
      (shRNAs) reduced virus titers in low-multiplicity infections. Consistent with
      these findings, analysis of virus-specific RNA in high-multiplicity infections
      indicated a reduction of viral RNA (vRNA) and mRNA after NXP2/MORC3
      downregulation. Silencing of NXP2/MORC3 in a recombinant minireplicon system in
      which virus transcription and replication are uncoupled showed reductions in cat
      mRNA and chloramphenicol acetyltransferase (CAT) protein accumulation but no
      alterations in cat vRNA levels, suggesting that NXP2/MORC3 is important for
      influenza virus transcription. IMPORTANCE: Influenza virus infections appear as
      yearly epidemics and occasional pandemics of respiratory disease, with high
      morbidity and occasional mortality. Influenza viruses are intracellular parasites
      that replicate and transcribe their genomic ribonucleoproteins in the nuclei of
      infected cells, in a complex interplay with host cell factors. Here we
      characterized the role of the human NXP2/MORC3 protein, a member of the
      Microrchidia family that is associated with the nuclear matrix, during virus
      infection. NXP2/MORC3 associates with the viral ribonucleoproteins in infected
      cells. Downregulation of NXP2/MORC3 reduced virus titers and accumulations of
      viral genomic RNA and mRNAs. Silencing of NXP2/MORC3 in an influenza virus CAT
      minireplicon system diminished CAT protein and cat mRNA levels but not genomic
      RNA levels. We propose that NXP2/MORC3 plays a role in influenza virus
      transcription.

PMID- 26202232
TI  - Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced
      Risk of Postnatal Mother-to-Child Transmission of HIV-1.
AB  - Infants born to HIV-1-infected mothers in resource-limited areas where
      replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1
      throughout breastfeeding. Despite this, the majority of infants do not contract
      HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This
      suggests that immune factors in breast milk of HIV-1-infected mothers help to
      limit vertical transmission. We compared the HIV-1 envelope-specific breast milk
      and plasma antibody responses of clade C HIV-1-infected postnatally transmitting
      and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding
      Antiretrovirals and Nutrition Study using multivariable logistic regression
      modeling. We found no association between milk or plasma neutralization activity,
      antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG
      responses and postnatal transmission risk. While the envelope-specific breast
      milk and plasma IgA responses also did not reach significance in predicting
      postnatal transmission risk in the primary model after correction for multiple
      comparisons, subsequent exploratory analysis using two distinct assay
      methodologies demonstrated that the magnitudes of breast milk total and secretory
      IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were
      associated with reduced postnatal transmission risk. These results suggest a
      protective role for mucosal HIV-1 envelope-specific IgA responses in the context
      of postnatal virus transmission. This finding supports further investigations
      into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via
      breast milk and into immune interventions aimed at enhancing this response.
      IMPORTANCE: Infants born to HIV-1-infected mothers are repeatedly exposed to the
      virus in breast milk. Remarkably, the transmission rate is low, suggesting that
      immune factors in the breast milk of HIV-1-infected mothers help to limit
      transmission. We compared the antibody responses in plasma and breast milk of HIV
      1-transmitting and -nontransmitting mothers to identify responses that correlated
      with reduced risk of postnatal HIV-1 transmission. We found that neither plasma
      nor breast milk IgG antibody responses were associated with risk of HIV-1
      transmission. In contrast, the magnitudes of the breast milk IgA and secretory
      IgA responses against HIV-1 envelope proteins were associated with reduced risk
      of postnatal HIV-1 transmission. The results of this study support further
      investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV
      1 transmission via breastfeeding and the development of strategies to enhance
      milk envelope-specific IgA responses to reduce mother-to-child HIV transmission
      and promote an HIV-free generation.

PMID- 26202234
TI  - Transcriptional Profiling of the Immune Response to Marburg Virus Infection.
AB  - Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic
      fever in humans and nonhuman primates. The mechanism of pathogenesis of the
      infection is not well understood, but it is well accepted that pathogenesis is
      appreciably driven by a hyperactive immune response. To better understand the
      overall response to Marburg virus challenge, we undertook a transcriptomic
      analysis of immune cells circulating in the blood following aerosol exposure of
      rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays,
      we analyzed the transcriptomes of peripheral blood mononuclear cells that were
      collected throughout the course of infection from 1 to 9 days postexposure,
      representing the full course of the infection. The response followed a 3-stage
      induction (early infection, 1 to 3 days postexposure; midinfection, 5 days
      postexposure; late infection, 7 to 9 days postexposure) that was led by a robust
      innate immune response. The host response to aerosolized Marburg virus was
      evident at 1 day postexposure. Analysis of cytokine transcripts that were
      overexpressed during infection indicated that previously unanalyzed cytokines are
      likely induced in response to exposure to Marburg virus and further suggested
      that the early immune response is skewed toward a Th2 response that would hamper
      the development of an effective antiviral immune response early in disease. Late
      infection events included the upregulation of coagulation-associated factors.
      These findings demonstrate very early host responses to Marburg virus infection
      and provide a rich data set for identification of factors expressed throughout
      the course of infection that can be investigated as markers of infection and
      targets for therapy. IMPORTANCE: Marburg virus causes a severe infection that is
      associated with high mortality and hemorrhage. The disease is associated with an
      immune response that contributes to the lethality of the disease. In this study,
      we investigated how the immune cells circulating in the blood of infected
      primates respond following exposure to Marburg virus. Our results show that there
      are three discernible stages of response to infection that correlate with
      presymptomatic, early, and late symptomatic stages of infection, a response
      format similar to that seen following challenge with other hemorrhagic fever
      viruses. In contrast to the ability of the virus to block innate immune signaling
      in vitro, the earliest and most sustained response is an interferon-like
      response. Our analysis also identifies a number of cytokines that are
      transcriptionally upregulated during late stages of infection and suggest that
      there is a Th2-skewed response to infection. When correlated with companion data
      describing the animal model from which our samples were collected, our results
      suggest that the innate immune response may contribute to overall pathogenesis.

PMID- 26202235
TI  - The Epstein-Barr Virus BDLF4 Gene Is Required for Efficient Expression of Viral
      Late Lytic Genes.
AB  - Epstein-Barr virus (EBV) is a gammaherpesvirus, associated with infectious
      mononucleosis and various types of malignancy. We focused here on the BDLF4 gene
      of EBV and identified it as a lytic gene, expressed with early kinetics. Viral
      late gene expression of the BDLF4 knockout strain was severely restricted; this
      could be restored by an exogenous supply of BDLF4. These results indicate that
      BDLF4 is important for the EBV lytic replication cycle, especially in late gene
      expression. 

PMID- 26202236
TI  - Protection from Severe Influenza Virus Infections in Mice Carrying the Mx1
      Influenza Virus Resistance Gene Strongly Depends on Genetic Background.
AB  - Influenza virus infections represent a serious threat to human health. Both
      extrinsic and intrinsic factors determine the severity of influenza. The MX
      dynamin-like GTPase 1 (Mx1) gene has been shown to confer strong resistance to
      influenza A virus infections in mice. Most laboratory mouse strains, including
      C57BL/6J, carry nonsense or deletion mutations in Mx1 and thus a nonfunctional
      allele, whereas wild-derived mouse strains carry a wild-type Mx1 allele. Congenic
      C57BL/6J (B6-Mx1(r/r)) mice expressing a wild-type allele from the A2G mouse
      strain are highly resistant to influenza A virus infections, to both mono- and
      polybasic subtypes. Furthermore, in genetic mapping studies, Mx1 was identified
      as the major locus of resistance to influenza virus infections. Here, we
      investigated whether the Mx1 protective function is influenced by the genetic
      background. For this, we generated a congenic mouse strain carrying the A2G wild
      type Mx1 resistance allele on a DBA/2J background (D2-Mx1(r/r)). Most remarkably,
      congenic D2-Mx1(r/r) mice expressing a functional Mx1 wild-type allele are still
      highly susceptible to H1N1 virus. However, pretreatment of D2-Mx1(r/r) mice with
      alpha interferon protected them from lethal infections. Our results showed, for
      the first time, that the presence of an Mx1 wild-type allele from A2G as such
      does not fully protect mice from lethal influenza A virus infections. These
      observations are also highly relevant for susceptibility to influenza virus
      infections in humans. IMPORTANCE: Influenza A virus represents a major health
      threat to humans. Seasonal influenza epidemics cause high economic loss,
      morbidity, and deaths each year. Genetic factors of the host strongly influence
      susceptibility and resistance to virus infections. The Mx1 (MX dynamin-like
      GTPase 1) gene has been described as a major resistance gene in mice and humans.
      Most inbred laboratory mouse strains are deficient in Mx1, but congenic B6
      Mx1(r/r) mice that carry the wild-type Mx1 gene from the A2G mouse strain are
      highly resistant. Here, we show that, very unexpectedly, congenic D2-Mx1(r/r)
      mice carrying the wild-type Mx1 gene from the A2G strain are not fully protected
      against lethal influenza virus infections. These observations demonstrate that
      the genetic background is very important for the protective function of the Mx1
      resistance gene. Our results are also highly relevant for understanding genetic
      susceptibility to influenza virus infections in humans.

PMID- 26202237
TI  - Experimental Evolution Identifies Vaccinia Virus Mutations in A24R and A35R That
      Antagonize the Protein Kinase R Pathway and Accompany Collapse of an Extragenic
      Gene Amplification.
AB  - Most new human infectious diseases emerge from cross-species pathogen
      transmissions; however, it is not clear how viruses adapt to productively infect
      new hosts. Host restriction factors represent one species-specific barrier that
      viruses may initially have little ability to inhibit in new hosts. For example,
      viral antagonists of protein kinase R (PKR) vary in their ability to block PKR
      mediated inhibition of viral replication, in part due to PKR allelic variation
      between species. We previously reported that amplification of a weak PKR
      antagonist encoded by rhesus cytomegalovirus, rhtrs1, improved replication of a
      recombinant poxvirus (VVDeltaEDeltaK+RhTRS1) in several resistant primate cells.
      To test whether amplification increases the opportunity for mutations that
      improve virus replication with only a single copy of rhtrs1 to evolve, we
      passaged rhtrs1-amplified viruses in semipermissive primate cells. After passage,
      we isolated two viruses that contained only a single copy of rhtrs1 yet
      replicated as well as the amplified virus. Surprisingly, rhtrs1 was not mutated
      in these viruses; instead, we identified mutations in two vaccinia virus (VACV)
      genes, A24R and A35R, either of which was sufficient to improve
      VVDeltaEDeltaK+RhTRS1 replication. Neither of these genes has previously been
      implicated in PKR antagonism. Furthermore, the mutation in A24R, but not A35R,
      increased resistance to the antipoxviral drug isatin-beta-thiosemicarbazone,
      suggesting that these mutations employ different mechanisms to evade PKR. This
      study supports our hypothesis that gene amplification may provide a "molecular
      foothold," broadly improving replication to facilitate rapid adaptation, while
      subsequent mutations maintain this efficient replication in the new host without
      requiring gene amplification. IMPORTANCE: Understanding how viruses adapt to a
      new host may help identify viruses poised to cross species barriers before an
      outbreak occurs. Amplification of rhtrs1, a weak viral antagonist of the host
      antiviral protein PKR, enabled a recombinant vaccinia virus to replicate in
      resistant cells from humans and other primates. After serial passage of rhtrs1
      amplified viruses, there arose in two vaccinia virus genes mutations that
      improved viral replication without requiring rhtrs1 amplification. Neither of
      these genes has previously been associated with inhibition of the PKR pathway.
      These data suggest that gene amplification can improve viral replication in a
      resistant host species and facilitate the emergence of novel adaptations that
      maintain the foothold needed for continued replication and spread in the new
      host.

PMID- 26202238
TI  - Intermolecular Complementation between Two Varicella-Zoster Virus pORF30
      Terminase Domains Essential for DNA Encapsidation.
AB  - The herpesviral terminase complex is part of the intricate machinery that
      delivers a single viral genome into empty preformed capsids (encapsidation). The
      varicella-zoster virus (VZV) terminase components (pORF25, pORF30, and pORF45/42)
      have not been studied as extensively as those of herpes simplex virus 1 and human
      cytomegalovirus (HCMV). In this study, VZV bacterial artificial chromosomes
      (BACs) were generated with small (Delta30S), medium (Delta30M), and large
      (Delta30L) ORF30 internal deletions. In addition, we isolated recombinant viruses
      with specific alanine substitutions in the putative zinc finger motif (30-ZF3A)
      or in a conserved region (region IX) with predicted structural similarity to the
      human topoisomerase I core subdomains I and II (30-IXAla, 30-620A, and 30-622A).
      Recombinant viruses replicated in an ORF30-complementing cell line (ARPE30) but
      failed to replicate in noncomplementing ARPE19 and MeWo cells. Transmission
      electron microscopy of 30-IXAla-, 30-620A-, and 30-622A-infected ARPE19 cells
      revealed only empty VZV capsids. Southern analysis showed that cells infected
      with parental VZV (VZVLUC) or a repaired virus (30R) contained DNA termini,
      whereas cells infected with Delta30L, 30-IXAla, 30-620A, or 30-622A contained
      little or no processed viral DNA. These results demonstrated that pORF30,
      specifically amino acids 619 to 624 (region IX), was required for DNA
      encapsidation. A luciferase-based assay was employed to assess potential
      intermolecular complementation between the zinc finger domain and conserved
      region IX. Complementation between 30-ZF3A and 30-IXAla provided evidence that
      distinct pORF30 domains can function independently. The results suggest that
      pORF30 may exist as a multimer or participate in higher-order assemblies during
      viral DNA encapsidation. IMPORTANCE: Antivirals with novel mechanisms of action
      are sought as additional therapeutic options to treat human herpesvirus
      infections. Proteins involved in the viral DNA encapsidation process have become
      promising antiviral targets. For example, letermovir is a small-molecule drug
      targeting HCMV terminase that is currently in phase III clinical trials. It is
      important to define the structural and functional characteristics of proteins
      that make up viral terminase complexes to identify or design additional terminase
      specific compounds. The VZV ORF30 mutants described in this study represent the
      first VZV terminase mutants reported to date. Targeted mutations confirmed the
      importance of a conserved zinc finger domain found in all herpesvirus ORF30
      terminase homologs but also identified a novel, highly conserved region (region
      IX) essential for terminase function. Homology modeling suggested that the
      structure of region IX is present in all human herpesviruses and thus represents
      a potential structurally conserved antiviral target.

PMID- 26202239
TI  - Transmission of H7N9 Influenza Viruses with a Polymorphism at PB2 Residue 627 in
      Chickens and Ferrets.
AB  - Poultry exposure is a major risk factor for human H7N9 zoonotic infections, for
      which the mode of transmission remains unclear. We studied the transmission of
      genetically related poultry and human H7N9 influenza viruses differing by four
      amino acids, including the host determinant PB2 residue 627. A/Silkie
      chicken/HK/1772/2014 (SCk1772) and A/HK/3263/14 (HK3263) replicated to comparable
      titers in chickens, with superior oropharyngeal over cloacal shedding; both
      viruses transmitted efficiently among chickens via direct contact but
      inefficiently via the airborne route. Interspecies transmission via the airborne
      route was observed for ferrets exposed to the SCk1772- or HK3263-infected
      chickens, while low numbers of copies of influenza viral genome were detected in
      the air, predominantly at particle sizes larger than 4 MUm. In ferrets, the human
      isolate HK3263 replicated to higher titers and transmitted more efficiently via
      direct contact than SCk1772. We monitored "intrahost" and "interhost" adaptive
      changes at PB2 residue 627 during infection and transmission of the Sck1772 that
      carried E627 and HK3263 that carried V/K/E polymorphism at 60%, 20%, and 20%,
      respectively. For SCk1772, positive selection for K627 over E627 was observed in
      ferrets during the chicken-to-ferret or ferret-to-ferret transmission. For HK3263
      that contained V/K/E polymorphism, mixed V627 and E627 genotypes were transmitted
      among chickens while either V627 or K627 was transmitted to ferrets with a narrow
      transmission bottleneck. Overall, our results suggest direct contact as the main
      mode for H7N9 transmission and identify the PB2-V627 genotype with uncompromised
      fitness and transmissibility in both avian and mammalian species. IMPORTANCE: We
      studied the modes of H7N9 transmission, as this information is crucial for
      developing effective control measures for prevention. Using chicken (SCk1772) and
      human (HK3263) H7N9 isolates that differed by four amino acids, including the
      host determinant PB2 residue 627, we observed that both viruses transmitted
      efficiently among chickens via direct contact but inefficiently via the airborne
      route. Chicken-to-ferret transmission via the airborne route was observed, along
      with the detection of viral genome in the air at low copy numbers. In ferrets,
      HK3263 transmitted more efficiently than SCk1772 via direct contact. During the
      transmission of SCk1772 that contained E and HK3263 that contained V/K/E
      polymorphism at PB2 residue 627, positive selections of E627 and K627 were
      observed in chickens and ferrets, respectively. In addition, PB2-V627 was
      transmitted and stably maintained in both avian and mammalian species. Our
      results support applying intervention strategies that minimize direct and
      indirect contact at the poultry markets during epidemics.

PMID- 26202240
TI  - Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry
      Site and Positively Regulates Viral Protein Translation.
AB  - Enterovirus 71 (EV71) recruits various cellular factors to assist in the
      replication and translation of its genome. Identification of the host factors
      involved in the EV71 life cycle not only will enable a better understanding of
      the infection mechanism but also has the potential to be of use in the
      development of antiviral therapeutics. In this study, we demonstrated that the
      cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an
      internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds
      specifically to the EV71 5' untranslated region (5'UTR). Interaction sites in
      both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear
      ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped
      using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown
      assay. More importantly, dual-luciferase (firefly) reporter analysis suggested
      that overexpression of Sam68 positively regulated IRES-dependent translation of
      virus proteins. In contrast, both IRES activity and viral protein translation
      significantly decreased in Sam68 knockdown cells compared with the negative
      control cells treated with short hairpin RNA (shRNA). However, downregulation of
      Sam68 did not have a significant inhibitory effect on the accumulation of the
      EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm
      and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2)
      and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic
      relocalization of Sam68 in EV71-infected cells may be involved in the enhancement
      of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding
      protein, these results provide direct evidence that Sam68 is a novel ITAF that
      interacts with EV71 IRES and positively regulates viral protein translation.
      IMPORTANCE: The nuclear protein Sam68 is found as an additional new host factor
      that interacts with the EV71 IRES during infection and could potentially enhance
      the translation of virus protein. To our knowledge, this is the first report that
      describes Sam68 actively participating in the life cycle of EV71 at a molecular
      level. These studies will not only improve our understanding of the replication
      of EV71 but also have the potential for aiding in developing a therapeutic
      strategy against EV71 infection.

PMID- 26202242
TI  - Puzzling Origins of the Ebola Outbreak in the Democratic Republic of the Congo,
      2014.

PMID- 26202241
TI  - Polyphenols Inhibit Hepatitis C Virus Entry by a New Mechanism of Action.
AB  - Despite the validation of direct-acting antivirals for hepatitis C treatment, the
      discovery of new compounds with different modes of action may still be of
      importance for the treatment of special patient populations. We recently
      identified a natural molecule, epigallocatechin-3-gallate (EGCG), as an inhibitor
      of hepatitis C virus (HCV) targeting the viral particle. The aim of this work was
      to discover new natural compounds with higher anti-HCV activity than that of EGCG
      and determine their mode of action. Eight natural molecules with structure
      similarity to EGCG were selected. HCV JFH1 in cell culture and HCV pseudoparticle
      systems were used to determine the antiviral activity and mechanism of action of
      the compounds. We identified delphinidin, a polyphenol belonging to the
      anthocyanidin family, as a new inhibitor of HCV entry. Delphinidin inhibits HCV
      entry in a pangenotypic manner by acting directly on the viral particle and
      impairing its attachment to the cell surface. Importantly, it is also active
      against HCV in primary human hepatocytes, with no apparent cytotoxicity and in
      combination with interferon and boceprevir in cell culture. Different approaches
      showed that neither aggregation nor destruction of the particle occurred. Cryo
      transmission electron microscopy observations of HCV pseudoparticles treated with
      delphinidin or EGCG showed a bulge on particles that was not observed under
      control conditions. In conclusion, EGCG and delphinidin inhibit HCV entry by a
      new mechanism, i.e., alteration of the viral particle structure that impairs its
      attachment to the cell surface. IMPORTANCE: In this article, we identify a new
      inhibitor of hepatitis C virus (HCV) infection, delphinidin, that prevents HCV
      entry. This natural compound, a plant pigment responsible for the blue-purple
      color of flowers and berries, belongs to the flavonoid family, like the catechin
      EGCG, the major component present in green tea extract, which is also an
      inhibitor of HCV entry. We studied the mode of action of these two compounds
      against HCV and demonstrated that they both act directly on the virus, inducing a
      bulging of the viral envelope. This deformation might be responsible for the
      observed inhibition of virus attachment to the cell surface. The discovery of
      such HCV inhibitors with an unusual mode of action is important to better
      characterize the mechanism of HCV entry into hepatocytes and to help develop a
      new class of HCV entry inhibitors.

PMID- 26202243
TI  - Inhibition of Ebola and Marburg Virus Entry by G Protein-Coupled Receptor
      Antagonists.
AB  - Filoviruses, consisting of Ebola virus (EBOV) and Marburg virus (MARV), are among
      the most lethal infectious threats to mankind. Infections by these viruses can
      cause severe hemorrhagic fevers in humans and nonhuman primates with high
      mortality rates. Since there is currently no vaccine or antiviral therapy
      approved for humans, there is an urgent need to develop prophylactic and
      therapeutic options for use during filoviral outbreaks and bioterrorist attacks.
      One of the ideal targets against filoviral infection and diseases is at the entry
      step, which is mediated by the filoviral glycoprotein (GP). In this report, we
      screened a chemical library of small molecules and identified numerous
      inhibitors, which are known G protein-coupled receptor (GPCR) antagonists
      targeting different GPCRs, including histamine receptors, 5-HT (serotonin)
      receptors, muscarinic acetylcholine receptor, and adrenergic receptor. These
      inhibitors can effectively block replication of both infectious EBOV and MARV,
      indicating a broad antiviral activity of the GPCR antagonists. The time-of
      addition experiment and microscopic studies suggest that GPCR antagonists block
      filoviral entry at a step following the initial attachment but prior to
      viral/cell membrane fusion. These results strongly suggest that GPCRs play a
      critical role in filoviral entry and GPCR antagonists can be developed as an
      effective anti-EBOV/MARV therapy. IMPORTANCE: Infection of Ebola virus and
      Marburg virus can cause severe illness in humans with a high mortality rate, and
      currently there is no FDA-approved vaccine or therapeutic treatment available.
      The 2013-2015 epidemic in West Africa underscores a lack of our understanding in
      the infection and pathogenesis of these viruses and the urgency of drug discovery
      and development. In this study, we have identified numerous inhibitors that are
      known G protein-coupled receptor (GPCR) antagonists targeting different GPCRs.
      These inhibitors can effectively block replication of both infectious EBOV and
      MARV, indicating a broad antiviral activity of the GPCR antagonists. Our results
      strongly suggest that GPCRs play a critical role in filoviral entry and GPCR
      antagonists can be developed as an effective anti-EBOV/MARV therapy.

PMID- 26202244
TI  - Determinants of Human CD134 Essential for Entry of Human Herpesvirus 6B.
AB  - We identified two key amino acid residues within human CD134 (hCD134) that are
      required for its interaction with human herpesvirus 6B (HHV-6B) and for HHV-6B
      entry into cells. One of the residues (K79) allows access of the HHV-6B ligand to
      hCD134. Murine CD134 (mCD134) functioned as an HHV-6B receptor when these two
      amino acid residues were replaced with homologous human residues. This study
      identifies both the HHV-6B receptor-ligand interaction and the species-specific
      determinants of hCD134 essential for HHV-6B entry. 

PMID- 26202245
TI  - Apolipoprotein E, but Not Apolipoprotein B, Is Essential for Efficient Cell-to
      Cell Transmission of Hepatitis C Virus.
AB  - Hepatitis C virus (HCV) infects hepatocytes through two different routes: (i)
      cell-free particle diffusion followed by engagement with specific cellular
      receptors and (ii) cell-to-cell direct transmission mediated by mechanisms not
      well defined yet. HCV exits host cells in association with very-low-density
      lipoprotein (VLDL) components. VLDL particles contain apolipoproteins B (ApoB)
      and E (ApoE), which are required for viral assembly and/or infectivity. Based on
      these precedents, we decided to study whether these VLDL components participate
      in HCV cell-to-cell transmission in vitro. We observed that cell-to-cell viral
      spread was compromised after ApoE interference in donor but not in acceptor
      cells. In contrast, ApoB knockdown in either donor or acceptor cells did not
      impair cell-to-cell viral transmission. Interestingly, ApoB participated in the
      assembly of cell-free infective virions, suggesting a differential regulation of
      cell-to-cell and cell-free HCV infection. This study identifies host-specific
      factors involved in these distinct routes of infection that may unveil new
      therapeutic targets and advance our understanding of HCV pathogenesis.
      IMPORTANCE: This work demonstrates that cell-to-cell transmission of HCV depends
      on ApoE but not ApoB. The data also indicate that ApoB is required for the
      assembly of cell-free infective particles, strongly suggesting the existence of
      mechanisms involving VLDL components that differentially regulate cell-free and
      cell-to-cell HCV transmission. These data clarify some of the questions regarding
      the role of VLDL in HCV pathogenesis and the transmission of the virus cell to
      cell as a possible mechanism of immune evasion and open the door to therapeutic
      intervention.

PMID- 26202246
TI  - Molecular Epidemiology and Evolution of Influenza Viruses Circulating within
      European Swine between 2009 and 2013.
AB  - The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex
      reassortant virus of swine origin, highlighted the importance of worldwide
      influenza virus surveillance in swine. To date, large-scale surveillance studies
      have been reported for southern China and North America, but such data have not
      yet been described for Europe. We report the first large-scale genomic
      characterization of 290 swine influenza viruses collected from 14 European
      countries between 2009 and 2013. A total of 23 distinct genotypes were
      identified, with the 7 most common comprising 82% of the incidence. Contrasting
      epidemiological dynamics were observed for two of these genotypes, H1huN2 and
      H3N2, with the former showing multiple long-lived geographically isolated
      lineages, while the latter had short-lived geographically diffuse lineages. At
      least 32 human-swine transmission events have resulted in A(H1N1)pdm09 becoming
      established at a mean frequency of 8% across European countries. Notably, swine
      in the United Kingdom have largely had a replacement of the endemic Eurasian
      avian virus-like ("avian-like") genotypes with A(H1N1)pdm09-derived genotypes.
      The high number of reassortant genotypes observed in European swine, combined
      with the identification of a genotype similar to the A(H3N2)v genotype in North
      America, underlines the importance of continued swine surveillance in Europe for
      the purposes of maintaining public health. This report further reveals that the
      emergences and drivers of virus evolution in swine differ at the global level.
      IMPORTANCE: The influenza A(H1N1)pdm09 virus contains a reassortant genome with
      segments derived from separate virus lineages that evolved in different regions
      of the world. In particular, its neuraminidase and matrix segments were derived
      from the Eurasian avian virus-like ("avian-like") lineage that emerged in
      European swine in the 1970s. However, while large-scale genomic characterization
      of swine has been reported for southern China and North America, no equivalent
      study has yet been reported for Europe. Surveillance of swine herds across Europe
      between 2009 and 2013 revealed that the A(H1N1)pdm09 virus is established in
      European swine, increasing the number of circulating lineages in the region and
      increasing the possibility of the emergence of a genotype with human pandemic
      potential. It also has implications for veterinary health, making prevention
      through vaccination more challenging. The identification of a genotype similar to
      the A(H3N2)v genotype, causing zoonoses at North American agricultural fairs,
      underlines the importance of continued genomic characterization in European
      swine.

PMID- 26202247
TI  - Modulation of Glycosaminoglycans Affects PrPSc Metabolism but Does Not Block
      PrPSc Uptake.
AB  - Mammalian prions are unconventional infectious agents composed primarily of the
      misfolded aggregated host prion protein PrP, termed PrP(Sc). Prions propagate by
      the recruitment and conformational conversion of cellular prion protein into
      abnormal prion aggregates on the cell surface or along the endocytic pathway.
      Cellular glycosaminoglycans have been implicated as the first attachment sites
      for prions and cofactors for cellular prion replication. Glycosaminoglycan
      mimetics and obstruction of glycosaminoglycan sulfation affect prion replication,
      but the inhibitory effects on different strains and different stages of the cell
      infection have not been thoroughly addressed. We examined the effects of a
      glycosaminoglycan mimetic and undersulfation on cellular prion protein
      metabolism, prion uptake, and the establishment of productive infections in L929
      cells by two mouse-adapted prion strains. Surprisingly, both treatments reduced
      endogenous sulfated glycosaminoglycans but had divergent effects on cellular PrP
      levels. Chemical or genetic manipulation of glycosaminoglycans did not prevent
      PrP(Sc) uptake, arguing against their roles as essential prion attachment sites.
      However, both treatments effectively antagonized de novo prion infection
      independently of the prion strain and reduced PrP(Sc) formation in chronically
      infected cells. Our results demonstrate that sulfated glycosaminoglycans are
      dispensable for prion internalization but play a pivotal role in persistently
      maintained PrP(Sc) formation independent of the prion strain. IMPORTANCE:
      Recently, glycosaminoglycans (GAGs) became the focus of neurodegenerative disease
      research as general attachment sites for cell invasion by pathogenic protein
      aggregates. GAGs influence amyloid formation in vitro. GAGs are also found in
      intra- and extracellular amyloid deposits. In light of the essential role GAGs
      play in proteinopathies, understanding the effects of GAGs on protein aggregation
      and aggregate dissemination is crucial for therapeutic intervention. Here, we
      show that GAGs are dispensable for prion uptake but play essential roles in
      downstream infection processes. GAG mimetics also affect cellular GAG levels and
      localization and thus might affect prion propagation by depleting intracellular
      cofactor pools.

PMID- 26202248
TI  - Reduced Simian Immunodeficiency Virus Replication in Macrophages of Sooty
      Mangabeys Is Associated with Increased Expression of Host Restriction Factors.
AB  - Macrophages are target cells of HIV/SIV infection that may play a role in AIDS
      pathogenesis and contribute to the long-lived reservoir of latently infected
      cells during antiretroviral therapy (ART). In previous work, we and others have
      shown that during pathogenic SIV infection of rhesus macaques (RMs), rapid
      disease progression is associated with high levels of in vivo macrophage
      infection. In contrast, during nonpathogenic SIV infection of sooty mangabeys
      (SMs), neither spontaneous nor experimental CD4(+) T cell depletion results in
      substantial levels of in vivo macrophage infection. To test the hypothesis that
      SM macrophages are intrinsically more resistant to SIV infection than RM
      macrophages, we undertook an in vitro comparative assessment of monocyte-derived
      macrophages (MDMs) from both nonhuman primate species. Using the primary isolate
      SIVM949, which replicates well in lymphocytes from both RMs and SMs, we found
      that infection of RM macrophages resulted in persistent SIV-RNA production while
      SIV-RNA levels in SM macrophage cultures decreased 10- to 100-fold over a similar
      temporal course of in vitro infection. To explore potential mechanisms
      responsible for the lower levels of SIV replication and/or production in
      macrophages from SMs we comparatively assessed, in the two studied species, the
      expression of the SIV coreceptor as well as the expression of a number of host
      restriction factors. While previous studies showed that SM monocytes express
      lower levels of CCR5 (but not CD4) than RM monocytes, the level of CCR5
      expression in MDMs was similar in the two species. Interestingly, we found that
      SM macrophages exhibited a significantly greater increase in the expression of
      tetherin (P = 0.003) and TRIM22 (P = 0.0006) in response to alpha interferon
      stimulation and increased expression of multiple host restriction factors in
      response to lipopolysaccharide stimulation and exposure to SIV. Overall, these
      findings confirm, in an in vitro infection system, that SM macrophages are
      relatively more resistant to SIV infection compared to RM macrophages, and
      suggest that a combination of entry and postentry restriction mechanisms may
      protect these cells from productive SIV infection. IMPORTANCE: This manuscript
      represents the first in vivo comparative analysis of monocyte-derived macrophages
      (MDMs) between rhesus macaques, i.e., experimental SIV hosts in which the
      infection is pathogenic and macrophages can be infected, and sooty mangabeys,
      i.e., natural SIV hosts in which the infection is nonpathogenic and macrophages
      are virtually never infected in vivo. This study demonstrates that mangabey
      derived MDMs are more resistant to SIV infection in vitro compared to macaque
      derived MDMs, and provides a potential explanation for this observation by
      showing increased expression of specific retrovirus restriction factors in
      mangabey-derived macrophages. Overall, this study is important as it contributes
      to our understanding of why SIV infection is nonpathogenic in sooty mangabeys
      while it is pathogenic in macaques, and is consistent with a pathogenic role for
      in vivo macrophage infection during pathogenic lentiviral infection.

PMID- 26202249
TI  - Genetic and Pathological Follow-Up Study of Goats Experimentally and Naturally
      Exposed to a Sheep Scrapie Isolate.
AB  - Thirty-seven goats carrying different prion protein genotypes (PRNP) were orally
      infected with a classical scrapie brain homogenate from wild-type (ARQ/ARQ) sheep
      and then mated to obtain 2 additional generations of offspring, which were kept
      in the same environment and allowed to be naturally exposed to scrapie.
      Occurrence of clinical or subclinical scrapie was observed in the experimentally
      infected goats (F0) and in only one (F1b) of the naturally exposed offspring
      groups. In both groups (F0 and F1b), goats carrying the R154H, H154H, R211Q, and
      P168Q-P240P dimorphisms died of scrapie after a longer incubation period than
      wild-type, G37V, Q168Q-P240P, and S240P goats. In contrast, D145D and Q222K goats
      were resistant to infection. The immunobiochemical signature of the scrapie
      isolate and its pathological aspects observed in the sheep donors were
      substantially maintained over 2 goat generations, i.e., after experimental and
      natural transmission. This demonstrates that the prion protein gene sequence,
      which is shared by sheep and goats, is more powerful than any possible but
      unknown species-related factors in determining scrapie phenotypes. With regard to
      genetics, our study confirms that the K222 mutation protects goats even against
      ovine scrapie isolates, and for the first time, a possible association of D145
      mutation with scrapie resistance is shown. In addition, it is possible that the
      sole diverse frequencies of these genetic variants might, at least in part, shape
      the prevalence of scrapie among naturally exposed progenies in affected herds.
      IMPORTANCE: This study was aimed at investigating the genetic and pathological
      features characterizing sheep-to-goat transmission of scrapie. We show that in
      goats with different prion protein gene mutations, the K222 genetic variant is
      associated with scrapie resistance after natural and experimental exposure to
      ovine prion infectivity. In addition, we observed for the first time a protective
      effect of the D145 goat variant against scrapie. Importantly, our results
      demonstrate that the phenotypic characteristic of the wild-type sheep scrapie
      isolate is substantially preserved in goats carrying different susceptible PRNP
      gene variants, thus indicating that the prion protein gene sequence, which is
      shared by sheep and goats, plays a fundamental role in determining scrapie
      phenotypes.

PMID- 26202251
TI  - A Novel PDZ Domain Interaction Mediates the Binding between Human Papillomavirus
      16 L2 and Sorting Nexin 27 and Modulates Virion Trafficking.
AB  - Previous studies have demonstrated an interaction between sorting nexin 17 and
      the L2 capsid proteins from a variety of papillomavirus types. This interaction
      is required for late endosomal trafficking of the L2 protein and entry of the
      L2/DNA complex into the nucleus during infection. Here we show an interaction
      between papillomavirus L2 proteins and the related PX-FERM family member sorting
      nexin 27 (SNX27), which is mediated in part by a novel interaction between the
      PDZ domain of SNX27 and sequences in a central portion of L2. The interaction is
      direct and, unlike that with SNX17, is variable in strength depending on the
      papillomavirus type. We show that small interfering RNA (siRNA)-mediated
      knockdown of SNX27 alone leads to a marginal reduction in the efficiency of viral
      infection but that double knockdown of both sorting nexins results in a striking
      reduction in infection, greater than that observed for the knockdown of either
      sorting nexin alone. These results suggest that the HPV L2 proteins can interact
      through distinct mechanisms with multiple components of the cellular cargo
      sorting machinery. IMPORTANCE: The trafficking of papillomaviruses to the host
      cell nucleus during their natural infectious life cycle is an incompletely
      understood process. Studies have suggested that the virus minor capsid protein L2
      can interact with the endosomal recycling pathway, in part by association with
      sorting nexin 17, to ensure that virus DNA bound to L2 is recycled through the
      trans-Golgi network rather than back to the plasma membrane. In this study, we
      characterize the interaction between L2 and a second sorting nexin, SNX27, which
      is also part of the retromer complex. The study furthers our understanding of
      papillomavirus infection dynamics and provides potential tools for the further
      dissection of endosomal structure and function.

PMID- 26202250
TI  - Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required
      To Survive a Natural Virus Infection.
AB  - Viruses that spread systemically from a peripheral site of infection cause
      morbidity and mortality in the human population. Innate myeloid cells, including
      monocytes, macrophages, monocyte-derived dendritic cells (mo-DC), and dendritic
      cells (DC), respond early during viral infection to control viral replication,
      reducing virus spread from the peripheral site. Ectromelia virus (ECTV), an
      orthopoxvirus that naturally infects the mouse, spreads systemically from the
      peripheral site of infection and results in death of susceptible mice. While
      phagocytic cells have a requisite role in the response to ECTV, the requirement
      for individual myeloid cell populations during acute immune responses to
      peripheral viral infection is unclear. In this study, a variety of myeloid
      specific depletion methods were used to dissect the roles of individual myeloid
      cell subsets in the survival of ECTV infection. We showed that DC are the primary
      producers of type I interferons (T1-IFN), requisite cytokines for survival,
      following ECTV infection. DC, but not macrophages, monocytes, or granulocytes,
      were required for control of the virus and survival of mice following ECTV
      infection. Depletion of either plasmacytoid DC (pDC) alone or the lymphoid
      resident DC subset (CD8alpha(+) DC) alone did not confer lethal susceptibility to
      ECTV. However, the function of at least one of the pDC or CD8alpha(+) DC subsets
      is required for survival of ECTV infection, as mice depleted of both populations
      were susceptible to ECTV challenge. The presence of at least one of these DC
      subsets is sufficient for cytokine production that reduces ECTV replication and
      virus spread, facilitating survival following infection. IMPORTANCE: Prior to the
      eradication of variola virus, the orthopoxvirus that causes smallpox, one-third
      of infected people succumbed to the disease. Following successful eradication of
      smallpox, vaccination rates with the smallpox vaccine have significantly dropped.
      There is now an increasing incidence of zoonotic orthopoxvirus infections for
      which there are no effective treatments. Moreover, the safety of the smallpox
      vaccine is of great concern, as complications may arise, resulting in morbidity.
      Like many viruses that cause significant human diseases, orthopoxviruses spread
      from a peripheral site of infection to become systemic. This study elucidates the
      early requirement for innate immune cells in controlling a peripheral infection
      with ECTV, the causative agent of mousepox. We report that there is redundancy in
      the function of two innate immune cell subsets in controlling virus spread early
      during infection. The viral control mediated by these cell subsets presents a
      potential target for therapies and rational vaccine design.

PMID- 26202252
TI  - Pim Kinase Interacts with Nonstructural 5A Protein and Regulates Hepatitis C
      Virus Entry.
AB  - The life cycle of hepatitis C virus (HCV) is highly dependent on host cellular
      proteins for virus propagation. In order to identify the cellular factors
      involved in HCV propagation, we performed protein microarray assay using the HCV
      nonstructural 5A (NS5A) protein as a probe. Of ~ 9,000 human cellular proteins
      immobilized in a microarray, approximately 90 cellular proteins were identified
      as NS5A interactors. Of these candidates, Pim1, a member of serine/threonine
      kinase family composed of three different isoforms (Pim1, Pim2, and Pim3), was
      selected for further study. Pim kinases share a consensus sequence which overlaps
      with kinase activity. Pim kinase activity has been implicated in tumorigenesis.
      In the present study, we verified the physical interaction between NS5A and Pim1
      by both in vitro pulldown and coimmunoprecipitation assays. Pim1 interacted with
      NS5A through amino acid residues 141 to 180 of Pim1. We demonstrated that protein
      stability of Pim1 was increased by NS5A protein and this increase was mediated by
      protein interplay. Small interfering RNA (siRNA)-mediated knockdown or
      pharmacological inhibition of Pim kinase abrogated HCV propagation. By employing
      HCV pseudoparticle entry and single-cycle HCV infection assays, we further
      demonstrated that Pim kinase was involved in HCV entry at a postbinding step.
      These data suggest that Pim kinase may represent a new host factor for HCV entry.
      IMPORTANCE: Pim1 is an oncogenic serine/threonine kinase. HCV NS5A protein
      physically interacts with Pim1 and contributes to Pim1 protein stability. Since
      Pim1 protein expression level is upregulated in many cancers, NS5A-mediated
      protein stability may be associated with HCV pathogenesis. Either gene silencing
      or chemical inhibition of Pim kinase abrogated HCV propagation in HCV-infected
      cells. We further showed that Pim kinase was specifically required at an early
      entry step of the HCV life cycle. Thus, we have identified Pim kinase not only as
      an HCV cell entry factor but also as a new anti-HCV therapeutic target.

PMID- 26202253
TI  - Alteration of Mature Nucleocapsid and Enhancement of Covalently Closed Circular
      DNA Formation by Hepatitis B Virus Core Mutants Defective in Complete-Virion
      Formation.
AB  - Assembly of hepatitis B virus (HBV) begins with packaging of the pregenomic RNA
      (pgRNA) into immature nucleocapsids (NC), which are converted to mature NCs
      containing the genomic relaxed circular (RC) DNA as a result of reverse
      transcription. Mature NCs have two alternative fates: (i) envelopment by viral
      envelope proteins, leading to secretion extracellularly as virions, or (ii)
      disassembly (uncoating) to deliver their RC DNA content into the host cell
      nucleus for conversion to the covalently closed circular (CCC) DNA, the template
      for viral transcription. How these two alternative fates are regulated remains to
      be better understood. The NC shell is composed of multiple copies of a single
      viral protein, the HBV core (HBc) protein. HBc mutations located on the surface
      of NC have been identified that allow NC maturation but block its envelopment.
      The potential effects of some of these mutations on NC uncoating and CCC DNA
      formation have been analyzed by transfecting HBV replication constructs into
      hepatoma cells. All envelopment-defective HBc mutations tested were competent for
      CCC DNA formation, indicating that core functions in envelopment and
      uncoating/nuclear delivery of RC DNA were genetically separable. Some of the
      envelopment-defective HBc mutations were found to alter specifically the
      integrity of mature, but not immature, NCs such that RC DNA became susceptible to
      nuclease digestion. Furthermore, CCC DNA formation could be enhanced by NC
      surface mutations that did or did not significantly affect mature NC integrity,
      indicating that the NC surface residues may be closely involved in NC uncoating
      and/or nuclear delivery of RC DNA. IMPORTANCE: Hepatitis B virus (HBV) infection
      is a major health issue worldwide. HBV assembly begins with the packaging into
      immature nucleocapsids (NCs) of a viral RNA pregenome, which is converted to the
      DNA genome in mature NCs. Mature NCs are then selected for envelopment and
      secretion as complete-virion particles or, alternatively, can deliver their DNA
      to the host cell nucleus to maintain the viral genome as nuclear episomes, which
      are the basis for virus persistence. Previous studies have identified mutations
      on the capsid surface that selectively block NC envelopment without affecting NC
      maturation. We have now discovered that some of the same mutations result in
      preferential alteration of mature NCs and increased viral nuclear episomes. These
      findings provide important new insights into the regulation of the two
      alternative fates of mature NCs and suggest new ways to perturb viral persistence
      by manipulating levels of viral nuclear episomes.

PMID- 26202254
TI  - Place of death in the population dying from diseases indicative of palliative
      care need: a cross-national population-level study in 14 countries.
AB  - BACKGROUND: Studying where people die across countries can serve as an evidence
      base for health policy on end-of-life care. This study describes the place of
      death of people who died from diseases indicative of palliative care need in 14
      countries, the association of place of death with cause of death,
      sociodemographic and healthcare availability characteristics in each country and
      the extent to which these characteristics explain country differences in the
      place of death. METHODS: Death certificate data for all deaths in 2008 (age >=1
      year) in Belgium, Canada, the Czech Republic, England, France, Hungary, Italy,
      Mexico, the Netherlands, New Zealand, South Korea, Spain (Andalusia), the USA and
      Wales caused by cancer, heart/renal/liver failure, chronic obstructive pulmonary
      disease, diseases of the nervous system or HIV/AIDS were linked with national or
      regional healthcare statistics (N=2,220,997). RESULTS: 13% (Canada) to 53%
      (Mexico) of people died at home and 25% (the Netherlands) to 85% (South Korea)
      died in hospital. The strength and direction of associations between home death
      and cause of death, sociodemographic and healthcare availability factors differed
      between countries. Differences between countries in home versus hospital death
      were only partly explained by differences in these factors. CONCLUSIONS: The
      large differences between countries in and beyond Europe in the place of death of
      people in potential need of palliative care are not entirely attributable to
      sociodemographic characteristics, cause of death or availability of healthcare
      resources, which suggests that countries' palliative and end-of-life care
      policies may influence where people die.

PMID- 26202255
TI  - Balancing the Osteogenic and Antibacterial Properties of Titanium by Codoping of
      Mg and Ag: An in Vitro and in Vivo Study.
AB  - To simultaneously enhance the osteogenic and antibacterial properties of
      titanium, we introduced magnesium (Mg), silver (Ag), or both by using the plasma
      immersion ion implantation (PIII) technique, producing three PIII sample groups,
      namely, Mg-doped titanium (Mg-PIII), Ag-doped titanium (Ag-PIII), and Mg and Ag
      codoped titanium (Mg/Ag-PIII). The in vitro antibacterial efficacy of Mg/Ag-PIII
      group was about 7-10% higher than that of Ag-PIII. In vitro and in vivo results
      demonstrated that osteogenic property of Mg/Ag PIII group was better than that of
      Ag-PIII or Mg-PIII. It was believed that the galvanic effects between Mg and Ag
      NPs played a key role in facilitating the release of Mg but reducing the release
      of silver, answering for the selective performances of the Mg/Ag-PIII group over
      bacterial and mammalian cells. This study demonstrated that the integration of
      multiple functional elements could be realized by the dual-source PIII technique,
      and in this case, the antibacterial properties and osteogenic property of
      titanium could be balanced. 

PMID- 26202256
TI  - Structurally Flexible C3-Symmetric Receptors for Molecular Recognition and Their
      Self-Assembly Properties.
AB  - The bioinspired design and synthesis of building blocks and their assemblies by
      the supramolecular approach has ever fascinated scientists to utilize such
      artificial systems for numerous purposes. Flexibility is a basic feature of
      natural systems. However, in artificial systems this is difficult to control,
      especially if there is no preorganization of the component(s) of a system. We
      have designed and synthesized a series of C3 -symmetric N-bridged flexible
      receptors and successfully utilized them to selectively entrap the notorious and
      toxic nitrate anion in aqueous medium. This was the first report of highest
      binding affinity for the nitrate anion in aqueous medium. An impressive self
      sorting phenomenon of reversibly formed hydrogen-bonded capsules, which self
      assembled from flexible tripodal receptors having branches of similar size and
      bearing the same amide functionality, has been disclosed. Encapsulated nitrate
      anion has been further utilized for the photochemical [2+2] cycloaddition
      reaction for the synthesis of strained four-membered ring structures through
      dynamic self-assembly. In this Personal Account, we summarize these results
      showing the utility of naturally inspired flexibility in artificial systems. 

PMID- 26202257
TI  - Dual-Time-Point FDG PET/CT to Distinguish Coccidioidal Pulmonary Nodules from
      Those Due to Malignancy.

PMID- 26202258
TI  - PACAP Modulates Expression of Hypoxia-Inducible Factors in Streptozotocin-Induced
      Diabetic Rat Retina.
AB  - Retinal hypoxia has been related to the pathogenesis of diabetic retinopathy.
      This event is mediated by the hypoxia-inducible factors (HIFs), including HIF
      1alpha, HIF-2alpha, and HIF-3alpha. Previously, we have demonstrated the
      protective role of pituitary adenylate cyclase-activating peptide (PACAP) in the
      early phase of diabetic retinopathy. In the present work, we investigated whether
      PACAP effect in hyperglycemic retina is mediated through modulation of HIFs'
      expression. Diabetes was induced with a single injection of streptozotocin (STZ)
      in rats. After 1 week, a group of diabetic animals was treated with a single
      intravitreal injection of 100 MUM PACAP or saline solution. Then, changes in
      HIFs' expression levels were evaluated in the retina after 3 weeks of
      hyperglycemia. The expression of HIF-1alpha and HIF-2alpha was significantly (p <
      0.001 vs control) increased in diabetic rats as compared to controls. Instead,
      their expression levels were significantly (p < 0.001 vs STZ) decreased after
      PACAP intraocular administration, as detected by Western blot analysis.
      Conversely, the expression of HIF-3alpha was significantly (p < 0.001 vs control)
      downregulated in retinas of STZ-injected rats and significantly (p < 0.001 vs
      control) increased after PACAP treatment. These data were supported by the
      immunohistochemical analysis. HIFs were localized either in inner and outer
      retinal layers. Diabetes interferes with their distribution, which is changed
      following intravitreal injection of PACAP. The present results suggest that the
      protective effect of the peptide in diabetic retina might be also mediated
      through modulation of HIFs' expression.

PMID- 26202259
TI  - Classes of Cell-Penetrating Peptides.
AB  - During the three decades of cell-penetrating peptides era the superfamily of CPPs
      has rapidly expanded, and the quest for new sequences continues. CPPs have been
      well recognized by scientific community and they have been used for transduction
      of a wide variety of molecules and particles into cultured cells and in vivo. In
      parallel with application of CPPs for delivering of active payloads, the
      mechanisms that such peptides take advantage of for gaining access to cells'
      insides have been in the focus of intense studies. Although the common
      denominator "cell penetration" unites all CPPs, the interaction partners on the
      cell surface, evoked cellular responses and even the uptake mechanisms might
      greatly vary between different peptide types. Here we present some possibilities
      for classification of CPPs based on their type of origin, physical-chemical
      properties, and the extent of modifications and design efforts. We also briefly
      analyze the internalization mechanisms with regard to their classification into
      groups based on physical-chemical characteristics. 

PMID- 26202260
TI  - Penetratin Story: An Overview.
AB  - Cell-penetrating peptides are short, often hydrophilic peptides that get access
      to the intracellular milieu. They have aroused great interest both in academic
      and applied research. First, cellular internalization of CPPs often involves the
      crossing of a biological membrane (plasma or vesicular), thus challenging the
      view of the non-permeability of these structures to large hydrophilic molecules.
      Secondly, CPPs can drive the internalization of hydrophilic cargoes into cells, a
      rate-limiting step in the development of many therapeutic substances.
      Interestingly, the two most used CPPs, TAT and penetratin peptides, are derived
      from natural proteins, HIV Tat and Antennapedia homeoprotein, respectively. The
      identification of the penetratin peptide, summarized in this review, is
      intimately linked to the study of its parental natural protein. 

PMID- 26202261
TI  - Prediction of Cell-Penetrating Peptides.
AB  - The in silico methods for the prediction of the cell-penetrating peptides are
      reviewed. Those include the multivariate statistical methods, machine-learning
      methods such as the artificial neural networks and support vector machines, and
      molecular modeling techniques including molecular docking and molecular
      dynamics.The applicability of the methods is demonstrated on the basis of the
      exemplary cases from the literature. 

PMID- 26202262
TI  - Computer-Aided Virtual Screening and Designing of Cell-Penetrating Peptides.
AB  - Cell-penetrating peptides (CPPs) have proven their potential as versatile drug
      delivery vehicles. Last decade has witnessed an unprecedented growth in CPP-based
      research, demonstrating the potential of CPPs as therapeutic candidates. In the
      past, many in silico algorithms have been developed for the prediction and
      screening of CPPs, which expedites the CPP-based research. In silico
      screening/prediction of CPPs followed by experimental validation seems to be a
      reliable, less time-consuming, and cost-effective approach. This chapter
      describes the prediction, screening, and designing of novel efficient CPPs using
      "CellPPD," an in silico tool. 

PMID- 26202263
TI  - Investigating Membrane Interactions and Structures of CPPs.
AB  - Despite many studies made on cell-penetrating peptides (CPPs), the mechanism of
      their cellular uptake and endosomal escape has not been completely resolved. This
      is even more unclear when the CPP is bound either covalently or non-covalently to
      the cargo molecules. To answer remaining questions, we require a combination of
      different methods, model systems, and experiments since there is no single method
      which could give a complete answer to all questions. Biophysical investigations
      of CPPs have a significant impact on CPP research considering their molecular
      mechanisms of action. In this chapter, we present different membrane model
      systems suitable for biophysical studies as well as the basic practical aspects
      underlying several common biophysical methods and experiments. The methods
      include fluorescence spectroscopy, circular dichroism spectroscopy, and dynamic
      light scattering and concern peptide-membrane interactions and vesicle model
      membrane leakage. We have also described the potential and limitations of
      biophysical studies on the CPP-membrane interactions and their impact on our
      understanding of how CPPs mediate the transport of cargoes into living cells. 

PMID- 26202264
TI  - Determining the Effects of Membrane-Interacting Peptides on Membrane Integrity.
AB  - In the study of cell-penetrating and membrane-translocating peptides, a
      fundamental question occurs as to the contribution arising from fundamental
      peptide-membrane interactions, relative to the contribution arising from the
      biology and energy of the cell, mostly occurring in the form of endocytosis and
      subsequent events. A commonly used approach to begin addressing these mechanistic
      questions is to measure the degree to which peptides can interact with, and
      physically disrupt, the integrity of synthetic lipid bilayers. Here, we describe
      a set of experimental methods that can be used to measure the potency, kinetics,
      transience, and the effective size of peptide-induced membrane disruption. 

PMID- 26202265
TI  - Study of CPP Mechanisms by Mass Spectrometry.
AB  - Studying the mechanisms of entry of cell-penetrating peptides (CPPs) requires
      reliable methods to measure their cellular uptake efficiency, monitor their
      metabolic stability, and identify their intracellular localization. We describe
      here a protocol based on the direct detection of peptides by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS),
      which allows the absolute quantification of the intact internalized species and
      the analysis of their intracellular degradation. This protocol can be easily
      applied to the simultaneous quantification of different species, for example
      mixtures of CPPs. 

PMID- 26202266
TI  - Methods to Study the Role of the Glycocalyx in the Uptake of Cell-Penetrating
      Peptides.
AB  - Cells are covered by a layer of negatively charged oligo- and polysaccharides,
      the glycocalyx. Cell-penetrating peptides and other drug delivery vehicles first
      encounter these polyanions before contacting the lipid bilayer of the plasma
      membrane. While a large body of data supports the notion that interactions with
      the glycocalyx promote or even trigger uptake, in some cases, the glycocalyx
      compromises delivery. As a consequence there is a need to address the role of the
      glycocalyx in delivery for each specific delivery vehicle and for each particular
      type of cell. Here, we describe protocols to obtain information on the
      composition and dynamics of the glycocalyx, and the role of individual glycocalyx
      components in the uptake of drug delivery vehicles. 

PMID- 26202267
TI  - Toxicity, Immunogenicity, Uptake, and Kinetics Methods for CPPs.
AB  - Cell-penetrating peptides (CPPs) have been utilized as delivery vectors for
      various payloads, both in vitro and in vivo. Similar issues as for any other drug
      delivery systems: cytotoxicity and the tendency to induce innate immune response
      may limit their applications in clinics. Therefore, assessment of cytotoxicity
      and immunogenicity is an important step toward characterization of applicability
      of these delivery vehicles. Studying internalization mechanisms and kinetics of
      CPPs provides important information for the development of novel and more
      efficient cellular delivery vectors. This chapter describes methods and protocols
      for investigation of cytotoxicity and immunogenic activities of CPPs in vitro and
      in vivo as well as methods for studying cellular uptake and internalization
      kinetics of CPPs. In the first section we describe methods for in vitro cell
      viability studies and ELISA assay, which allows to measure cytokine release in
      cell culture media and in blood serum in response to different CPP applications.
      This chapter also provides a protocol for assessing caspase-1 activity essential
      for inflammation. In the second section of this chapter, we describe a
      comprehensive method and protocol for determining the endocytosis mechanisms
      utilized in CPP uptake by using luciferin-CPP conjugates and endocytosis
      inhibitors. 

PMID- 26202268
TI  - Unraveling the Mechanisms of Peptide-Mediated Delivery of Nucleic Acids Using
      Electron Microscopy.
AB  - Cell-penetrating peptides (CPPs) are efficient non-viral delivery vectors for
      bioactive cargos, both in vitro and in vivo. Cargo molecules can be attached to
      CPPs either via covalent conjugation or by complex formation using co-incubation,
      which is typically used for charged molecules such as nucleic acids. The latter
      technique is efficiently used in case of CADY, MPG, Pep peptides, NickFects and
      PepFects that condense oligonucleotides (ONs) into nanoparticles, which
      efficiently enter cells and induce biological effects. Despite being highly
      promising candidates for developing new-generation medicines, CPPs'
      internalization mechanisms and intracellular trafficking are still far from being
      well-understood, and obtained data are often controversial. Transmission electron
      microscopy (TEM) is an informative and valuable tool for examining the mechanisms
      of CPP-ON nanoparticles. TEM enables to visualize nanoparticles or single
      molecules labeled with NanogoldTM tag, and follow their association with cells
      and intracellular localization. In this chapter, we present methods for
      preparation of CPP-ON nanoparticles for TEM analysis and for examination of their
      interactions with the plasma membrane, and subsequent cellular uptake either by
      direct translocation or endocytosis. In case of endocytosis, ONs have to be
      released from endosomes and reach their target site in nucleus or cytoplasm to
      reveal their activity. TEM enables to estimate when the endosomal escape begins,
      from which type of endosomal vesicles it occurs, whether the vesicles are broken,
      or nanocomplexes translocate across the membrane into cytosol. Since single ONs
      could be followed, the time-frame that is necessary for the splice-switching
      nucleotides to translocate into cell nucleus can be analyzed by TEM.

PMID- 26202269
TI  - SCARA Involvement in the Uptake of Nanoparticles Formed by Cell-Penetrating
      Peptides.
AB  - The investigation of uptake mechanisms for cell-penetrating peptides (CPPs) is
      and has been an ongoing project for as long as the peptides have been known, a
      time period that now spans over two decades. The ultimate answer is yet to be
      revealed and the current understanding is that no "one" mechanism will ever be
      found. The reason for this is that the uptake mechanism seems to be dependent on
      a multitude of factors that include which CPP, what cells are used, whether or
      not there is cargo and what the cargo is. CPPs are capable of delivering a
      variety of bio-macromolecules that are by themselves unable to enter into cells.
      Our group has reported on many different peptides in recent years, many aimed at
      delivering various oligonucleotide-based cargoes. These peptides have utilized
      the inherent positive charge of the peptides and some rationally designed
      modifications to non-covalently complex oligonucleotides and bring them into
      cells. In this chapter, we present a brief overview of the current proposals for
      the uptake mechanisms of CPPs and describe methods for detecting and evaluating
      the role of scavenger receptor class A receptors in the uptake of non-covalent
      cell-penetrating peptide:oligonucleotide complexes. 

PMID- 26202270
TI  - Protein Mimicry and the Design of Bioactive Cell-Penetrating Peptides.
AB  - The multi-domain architecture of many human proteins provides a structural basis
      for the physical maintenance of interactomes, or networks of protein-protein
      interactions (PPIs), that are so obviously crucial to cellular functions.
      Moreover, the structural and electrostatic complementarity provided by PPI
      interfaces, predominantly located on protein surfaces, is a fundamental component
      of signal transduction events that are known to be compromised in human diseases
      including many cancers.The pharmacokinetic advantages provided by cell
      penetrating peptides (CPPs) are entirely compatible with the development of
      intrinsically permeable agents capable of modulating intracellular PPIs. Thus,
      the term bioportide is a useful descriptor of numerous bioactive CPPs that are
      distinct from the more usual inert CPP vectors. Herein we illustrate a generic
      strategy, predominantly centered upon the identification of cationic peptides
      derived from helical protein domains, which offers a reliable platform to
      identify bioportides capable of modulating intracellular signal transduction
      events. In addition, we describe robust methodologies to determine the precise
      intracellular distribution of fluorescent bioportides and present assays
      routinely employed to screen for the detrimental pharmacodynamic properties often
      exhibited by both CPPs and bioportides; namely adverse cytotoxicity and the
      receptor-independent stimulation of mast cell secretion. 

PMID- 26202272
TI  - Identification and Characterization of Homing Peptides Using In Vivo Peptide
      Phage Display.
AB  - Each normal organ and pathological condition expresses a distinct set of
      molecules on their vasculature. These molecular signatures have been efficiently
      profiled using in vivo phage display. Several peptides homing to tumor blood
      vessels, lymphatic vessels, and/or tumor cells as well as to various normal
      organs have been isolated using this method. The in vivo screening of phage
      libraries has also revealed novel tissue-specific biomarkers of the normal and
      diseased vasculature. Tumor-homing peptides have been successfully used to target
      therapeutics and imaging agents to tumors. In vivo phage display has also been
      used in the identification of cell and/or tumor type-specific cell-penetrating
      peptides, which further facilitate the transmembrane delivery of various cargo
      molecules into cells. In this review we describe experimental setup for a
      combined ex vivo and in vivo screening procedure to select both conventional and
      cell-penetrating peptides homing to brain tumors. 

PMID- 26202271
TI  - Pepducins and Other Lipidated Peptides as Mechanistic Probes and Therapeutics.
AB  - Lipopeptides based on the intracellular loops of cell-surface receptors, known as
      "Pepducins," represent a promising new class of compounds used for the study of
      membrane proteins and as potential therapeutics in a variety of diseases.
      Detailed knowledge of the three-dimensional structure of G-protein-coupled
      receptors (GPCRs) and delineation of the mechanisms of pepducin activation and
      biased G-protein signaling has facilitated the development of even more potent
      pepducin allosteric modulators. 

PMID- 26202273
TI  - The Antimicrobial and Antiviral Applications of Cell-Penetrating Peptides.
AB  - Over the past two decades, cell-penetrating peptides (CPPs) have become
      increasingly popular both in research and in application. There have been
      numerous studies on the physiochemical characteristics and behavior of CPPs in
      various environments; likewise, the mechanisms of entry and delivery capabilities
      of these peptides have also been extensively researched. Besides the fundamental
      issues, there is an enormous interest in the delivery capabilities of the
      peptides as the family of CPPs is a promising and mostly non-toxic delivery
      vector candidate for numerous medical applications such as gene silencing,
      transgene delivery, and splice correction. Lately, however, there has been an
      emerging field of study besides the high-profile gene therapy applications-the
      use of peptides and CPPs to combat various infections caused by harmful bacteria,
      fungi, and viruses.In this chapter, we aim to provide a short overview of the
      history and properties of CPPs which is followed by more thorough descriptions of
      antimicrobial and antiviral peptides. To achieve this, we analyze the origin of
      such peptides, give an overview of the mechanisms of action and discuss the
      various practical applications which are ongoing or have been suggested based on
      research. 

PMID- 26202274
TI  - Visualizing Actin Architectures in Cells Incubated with Cell-Penetrating
      Peptides.
AB  - Defining the exact role of the actin cytoskeleton in mediating endocytosis
      through different pathways is a significant challenge. The general consensus is
      that actin has an important role in organizing the early stages of endocytosis
      but there is still much to learn. Actin has also been implicated in cell
      internalization of cell-penetrating peptides (CPPs). It is suggested that CPP
      variants such as octaarginine (R8) and the HIV Tat peptide induce actin-dependent
      plasma membrane perturbation and enter via macropinocytosis. Here, we describe
      confocal microscopy techniques that allow for high-resolution spatial
      characterization of the actin cytoskeleton in untreated mammalian cells and those
      incubated with actin-disrupting agents and CPPs. By performing X-Y-Z projection
      images through different regions of cells to show basal and apical profiles, we
      initially highlight how these techniques can be used to reveal major differences
      in cortical and filamentous actin organization between different cell lines.
      Using these techniques, we demonstrate that the actin-disrupting agent
      cytochalasin D rapidly changes this framework at concentrations significantly
      lower than is normally used. Experiments are also performed to highlight that
      serum starvation significantly sensitizes cells to the effects of R8 on actin
      induced ruffling and lamellapodia formation. The techniques described here can be
      used to gain a higher level of knowledge of the organization of the actin network
      in individual model cell systems, how this is perturbed using commonly used actin
      inhibitors, and how plasma membrane reorganization can be induced by the addition
      of drug delivery vectors such as CPPs.

PMID- 26202275
TI  - Cell-Penetrating Peptides as Carriers for Transepithelial Drug Delivery In Vitro.
AB  - There is a growing interest in the use of cell-penetrating peptides (CPPs) as
      carriers for transepithelial drug delivery. This chapter gives an introduction to
      and discussion of the commonly used production and characterization methods for
      CPP-cargo samples including high-throughput cell viability screening. Moreover,
      we describe methods for permeation and cell viability assessment in the Caco-2
      cell culture model with and without implementation of biosimilar mucus. Last, a
      method to assess metabolic degradation in vitro is described. 

PMID- 26202276
TI  - A Pathway Toward Tumor Cell-Selective CPPs?
AB  - Despite the great potential of CPPs in therapeutics and diagnosis, their
      application still suffers from a non-negligible drawback: a complete lack of cell
      type specificity. In the innumerous routes proposed for CPP cell entry there is
      common agreement that electrostatic interactions between cationic CPPs and
      anionic components in membranes, including lipids and glycosaminoglycans, play a
      crucial role. Tumor cells have been shown to overexpress certain
      glycosaminoglycans at the cell membrane surface and to possess a higher amount of
      anionic lipids in their outer leaflet when compared with healthy cells. Such
      molecules confer tumor cell membranes an enhanced anionic character, a property
      that could be exploited by CPPs to preferentially target these cells. Herein,
      these aspects are discussed in an attempt to confer CPPs certain selectivity
      toward cancer cells. 

PMID- 26202277
TI  - PepFects and NickFects for the Intracellular Delivery of Nucleic Acids.
AB  - Nucleic acids can be utilized in gene therapy to restore, alter, or silence gene
      functions. In order to reveal the biological activity nucleic acids have to reach
      their intracellular targets by passing through the plasma membrane, which is
      impermeable for these large and negatively charged molecules. Cell-penetrating
      peptides (CPPs) condense nucleic acids into nanoparticles using non-covalent
      complexation strategy and mediate their delivery into the cell, whereas the
      physicochemical parameters of the nanoparticles determine the interactions with
      the membranes, uptake mechanism, and subsequent intracellular fate. The
      nanoparticles are mostly internalized by endocytosis that leads to the entrapment
      of them in endosomal vesicles. Therefore design of new CPPs that are applicable
      for non-covalent complex formation strategy and harness endosomolytic properties
      is highly vital. Here we demonstrate that PepFects and NickFects are efficient
      vectors for the intracellular delivery of various nucleic acids.This chapter
      describes how to form CPP/pDNA nanoparticles, evaluate stable nanoparticles
      formation, and assess gene delivery efficacy.

PMID- 26202278
TI  - In Vitro Assays to Assess Exon Skipping in Duchenne Muscular Dystrophy.
AB  - Cell-penetrating peptide (CPP)-mediated delivery of phosphorodiamidate morpholino
      oligomers (PMO) results in efficient exon skipping and has shown great promise as
      a potential therapy for Duchenne muscular dystrophy (DMD). However, large
      differences in efficiency have been observed between CPPs and in delivery to
      different tissues. Cellular trafficking has appeared to be an important
      determinant of activity. This chapter provides details of experimental procedures
      to monitor exon skipping efficiency and cellular trafficking of Pip6a-PMO, a
      recently developed and particularly efficient conjugate, in skeletal H2k cells
      and in primary cardiomyocytes from mdx mice. Similar procedures may be used in
      principle to evaluate any free or vector-associated oligonucleotide for exon
      skipping. 

PMID- 26202279
TI  - Applications of ApoB LDLR-Binding Domain Approach for the Development of CNS
      Penetrating Peptides for Alzheimer's Disease.
AB  - Delivery of protein therapeutics to the CNS has proven to be a challenge to due
      to the presence of the blood-brain barrier (BBB), which prevents the passage of
      most proteins and large molecules from invading the neuronal space. Recently, we,
      and others, have developed technologies to circumvent this barrier by targeting
      receptors on the surface of the endothelial cells of the BBB to facilitate
      transport of therapeutic proteins. We describe here one such approach for
      targeting the LDLR by fusion of 38 amino acids from the ApoB protein to a
      therapeutic protein. 

PMID- 26202280
TI  - CPP-Based Delivery System for In Vivo Gene Delivery.
AB  - The method presents most important steps in estimating a CPP-mediated reporter
      gene delivery in a mouse model. The method is applicable for administrating
      noncovalent CPP/pDNA complexes via i.v. injection and for analysis of luciferase
      levels in tissue homogenates. This method could be extended to analyze the
      delivery of different nucleic acid cargos with other types of delivery vectors.
      First, a simple method is presented for assessing the stability of complexes in
      blood after i.v. administration, based on quantitation of a fluorescently labeled
      nucleic acid. Secondly, a protocol is presented for assessing and analyzing
      luciferase levels in mouse organs.

PMID- 26202281
TI  - Application of CPPs for Brain Delivery.
AB  - Cell-penetrating peptides provide a promising strategy for delivery of drugs
      across the blood-brain barrier. Here, we present an overview of CPP and peptide
      mediated delivery to the central nervous system as well as a Transwell in vitro
      model to evaluate passage across an endothelial cell layer mimic of the blood
      brain barrier. 

PMID- 26202282
TI  - Intracellular Delivery of Nanoparticles with Cell Penetrating Peptides.
AB  - The functionalization of nanoparticles (NPs) with cell penetrating peptides
      (CPPs) constitutes a breakthrough for the intracellular delivery of therapeutic
      and diagnostic payloads. In late 1998, a significant cellular uptake of a small
      protein from the HIV-1 virus, namely TAT peptide (TATp), was observed.
      Thereafter, research began on design of similarly acting peptides, and the
      coupling of NPs with these novel CPPs. Here, we describe recent methods used to
      modify the surface of NPs with CPPs and the in vitro and in vivo effects of such
      functionalization on the intracellular delivery of various cargos. In particular,
      we highlight recent advances aimed at reducing the non-selectivity of CPPs and
      the prevention of their enzymatic cleavage en route to target tissues.

PMID- 26202283
TI  - Multifunctional Oligoaminoamides for the Receptor-Specific Delivery of
      Therapeutic RNA.
AB  - Drugs with novel and versatile modes of action, such as therapeutic nucleic acids
      or proteins, open new possibilities for the precise therapy of different
      diseases. The most crucial limitation during the development of a therapeutic
      drug remains the safe and efficient intracellular delivery.To overcome the
      hurdles and to realize the successful delivery of such new biopharmaceuticals,
      our laboratory has recently developed a sequence-defined, cationic oligomer
      platform based on solid-phase synthesis. These multifunctional oligomers have
      displayed efficient delivery of therapeutic RNA in vitro and in vivo. In this
      chapter, we provide a brief background on the special features and applications
      of these carrier systems as well as detailed protocols for the oligomer and
      polyplex synthesis and their evaluation. 

PMID- 26202284
TI  - Cell Penetrating Peptides for Chemical Biological Studies.
AB  - Significant progress has been made in the development of chemical biology methods
      used to study the molecular behavior and interplay among live cells. These
      include the development of novel fluorescent molecules and photo-cross-linking
      agents that can be used to determine the cellular locations of biomacromolecules
      (including proteins and nucleic acids). Various biosensors utilizing the
      remarkable ligand-recognition abilities of biomacromolecules have also been
      developed. To allow such chemically functionalized molecules to interact with
      their partners, and to fully exploit the abilities and functions thereof, it is
      necessary to efficiently deliver such molecules into cells, specifically into the
      cytosol. Here, we illustrate intracellular delivery methods employing arginine
      rich cell-penetrating peptides (CPPs) (e.g., octa-arginine) in the presence of a
      counteranion, pyrenebutyrate. This approach is especially suitable for
      intracellular delivery of small proteins and peptides. Approaches employing
      arginine-rich CPPs tagged with a penetration-accelerating sequence can also be
      used toward this end. 

PMID- 26202285
TI  - Experiences with CPP-Based Self Assembling Peptide Systems for Topical Delivery
      of Botulinum Toxin.
AB  - Considerations in rational designs of CPP-based transcutaneous delivery systems
      are described. Impact of design considerations of nonclinical and clinical
      results are presented in detail. 

PMID- 26202286
TI  - Applications of CPPs in Genome Modulation of Plants.
AB  - Cell-penetrating peptides (CPPs) are a class of short peptides that are known to
      translocate inside living cells through the cell membrane. Many CPPs show an
      ability to bind and deliver macromolecular cargoes such as DNA, RNA and protein
      into living cells, making them excellent transfection and transduction agents
      with low cytotoxicity. While their use is well established in mammalian cell
      systems, they have also been explored in the last decade as transfection agents
      in plant cells. Their efficacy has been demonstrated in both monocot and dicot
      clades as well as a variety of tissues and cell cultures, from leaves to
      protoplasts. Factors affecting CPP and CPP-cargo uptake have been addressed with
      specific attention to the plant cell wall and classes of CPPs utilized in plant
      cell systems. It has been shown that internalization of most free peptides in
      plant cells has been dominated by direct translocation across the cell membrane,
      while CPP-macromolecular cargo complexes and conjugates were translocated via
      macropinocytosis. Moreover, functionalization of CPPs resulted in generation of
      peptides with specialized cargo delivery attributes, e.g., for specific
      subcellular targeting. Thus, the use of CPPs in plants presents a promising
      method for plant transgenesis as well as genome regulation and modification. 

PMID- 26202287
TI  - DNA Transfer into Animal Cells Using Stearylated CPP Based Transfection Reagent.
AB  - The efficient transfection of cloned genes into cells has a critical role in
      nucleic acid-based therapeutic applications, molecular and cell biology studies,
      and the production of recombinant proteins in cultured cells. Using a stearylated
      cell-penetrating peptide (CPP) NickFect51, we have generated an effective,
      universal, and convenient method for the delivery of DNA vectors into animal
      cells derived from different origins (mammalian, avian, insect). The CPP-mediated
      transfection described in detail herein is efficient for many regular cell lines
      commonly used for research purposes and it is especially suitable for
      transfection of protein production cell lines adapted for growth in chemically
      defined serum-free medium. 

PMID- 26202288
TI  - Live Cell Genomics: Cell-Specific Transcriptome Capture in Live Tissues and
      Cells.
AB  - The sensitivity of new transcriptomic techniques is rapidly improving to the
      point that single-cell molecular analysis is now becoming commonplace. However to
      obtain accurate transcriptome data, the initial experimental steps must strive to
      maintain the natural environment of cell and always get set in motion under in
      vivo conditions. Achieving these critical experimental parameters is technically
      challenging for investigators and currently the most frequently used molecular
      techniques experimentally commence with tissues or cells in artificial
      environments or under in vitro conditions. Here we review an innovative
      experimental approach that is called transcriptome in vivo analysis (TIVA) that
      was designed to overcome theses well-known limitations. The TIVA methods permit
      cell-specific transcriptome capture from viable intact heterogeneous tissues.
      Cell-penetrating peptides (CPPs) are used to deliver multifunctional
      transcriptome-capture tags (TIVA tags) to the cytoplasm of the cell under in vivo
      conditions. The TIVA capture tag enables investigators to target and isolate cell
      specific transcriptomes in their natural microenvironments. The combination of
      maintaining in vivo conditions and selective cell-specific transcriptome capture
      provides investigators with the opportunity to yield the most biologically
      accurate and informative transcriptome data hitherto. 

PMID- 26202289
TI  - Live Cell Genomics: RNA Exon-Specific RNA-Binding Protein Isolation.
AB  - RNA-binding proteins (RBPs) are essential regulatory proteins that control all
      modes of RNA processing and regulation. New experimental approaches to isolate
      these indispensable proteins under in vivo conditions are needed to advance the
      field of RBP biology. Historically, in vitro biochemical approaches to isolate
      RBP complexes have been useful and productive, but biological relevance of the
      identified RBP complexes can be imprecise or erroneous. Here we review an
      inventive experimental to isolate RBPs under the in vivo conditions. The method
      is called peptide nucleic acid (PNA)-assisted identification of RBP (PAIR)
      technology and it uses cell-penetrating peptides (CPPs) to deliver photo
      activatible RBP-capture molecule to the cytoplasm of the live cells. The PAIR
      methodology provides two significant advantages over the most commonly used
      approaches: (1) it overcomes the in vitro limitation of standard biochemical
      approaches and (2) the PAIR RBP-capture molecule is highly selective and
      adaptable which allows investigators to isolate exon-specific RBP complexes. Most
      importantly, the in vivo capture conditions and selectivity of the RBP-capture
      molecule yield biologically accurate and relevant RBP data.

PMID- 26202290
TI  - Distal Enteral Feeding Helps Blood Sugar Control in Pancreatectomized Patients.
AB  - BACKGROUND: The change in the route of food passage after pancreaticoduodenectomy
      (PD) is quite similar to the change after gastric bypass surgery; both procedures
      bypass the duodenum and directly connect to the distal jejunum. Moreover, both
      procedures result in resolution of type 2 diabetes mellitus. Therefore, more
      distal enteral anastomosis after PD may further improve glycemic status. METHODS:
      To test the effect of distal enteral feeding on glucose metabolism in patients
      after PD, we performed a meal test on 20 patients via a nasogastric tube
      [proximal feeding group (PFG)] on post-operative day 5 and then via an intra
      operatively placed jejunostomy feeding tube [distal feeding group (DFG)] on post
      operative day. Blood samples were assessed for hormones and glucose. RESULTS: The
      AUC0-120 min levels of GLP-1, C-peptide, and insulin after distal feeding were
      significantly higher than after proximal feeding. The AUC0-120 min levels of
      glucose in the DFG were significantly lower than in the PFG. CONCLUSIONS: More
      distal enteral feeding contributed to better glucose metabolism after PD.

PMID- 26202291
TI  - Epidemiology and risk factors of nonalcoholic fatty liver disease (NAFLD).
AB  - The nonalcoholic fatty liver disease (NAFLD) is defined as the presence of
      hepatic steatosis, determined by either imaging or histology, in the absence of
      secondary causes of hepatic fat accumulation. Nonalcoholic fatty liver is defined
      as the presence of hepatic steatosis with no evidence of hepatocellular injury in
      the form of ballooning of the hepatocytes or fibrosis. NASH is defined as the
      presence of hepatic steatosis and inflammation with hepatocyte injury
      (ballooning) with or without fibrosis. Although initial epidemiological studies
      have focused on its prevalence in the Western countries, it is becoming
      increasingly clear that NAFLD is highly prevalent in the Asia Pacific region, and
      there may be important distinctions in its phenotype between Asia Pacific and
      Western countries. Of particular interest are "lean NAFLD" and the "urban-rural
      divide," which will be discussed in this review article. Obesity, dyslipidemia,
      type 2 diabetes and metabolic syndrome are established risk factors for
      developing NAFLD. Many other risk factors (e.g., hypothyroidism, polycystic ovary
      syndrome, obstructive sleep apnea, hypopituitarism and hypogonadism) for NAFLD
      have been described in the Western countries, but these associations are yet to
      be investigated adequately in the Asia Pacific region. 

PMID- 26202292
TI  - Current histological classification of NAFLD: strength and limitations.
AB  - Nonalcoholic fatty liver disease (NAFLD) covers a spectrum of lesions ranging
      from pure steatosis without significant necroinflammatory injury (NAFL) to a
      complex pattern with lesions of hepatocyte injury and inflammation (nonalcoholic
      steatohepatitis, NASH) in the absence of significant alcohol intake. Because
      histopathological evaluation of liver biopsy samples remains central in NAFLD in
      the absence of a non-invasive test with enough accuracy, precise definition of
      each group is a key issue. When at least 5 % of hepatocytes display steatosis,
      patients can be qualified for NAFLD in an appropriate clinical context. When, in
      addition, lobular inflammation and liver cell clarification/ballooning are
      present, then the lesion can be qualified for NASH. Like for other chronic liver
      diseases, semiquantitative histological scoring has been proposed for NAFLD.
      These scoring systems are not useful in clinical practice, and each has some
      limitation. For comprehensive purposes, we suggest describing histopathological
      lesions in NAFLD using the SAF score, which assesses together and separately (1)
      the grade of steatosis (S, from S0 to S3) and (2) the grade of activity (A from
      A0 to A4 by adding the grades of ballooning and lobular inflammation, both from 0
      to 2) and the stage of fibrosis (F from F0 to F4). Such a semiquantitative score
      could be used for assessing changes in paired biopsies spontaneously or during
      clinical trials. Finally, the SAF score could help to correctly describe
      borderline cases of fatty liver diseases that do not fulfill all of the
      diagnostic criteria of simple steatosis or steatohepatitis, but as for any
      scoring system, a comprehensive description of the different lesions in their
      appropriate context is still necessary. 

PMID- 26202293
TI  - Hard clinical outcomes in patients with NAFLD.
AB  - Non-alcoholic fatty liver disease (NAFLD), once regarded as an innocuous
      condition, is now considered to be the most common cause of chronic liver disease
      worldwide. Evidence suggests a strong association between NAFLD and other
      potentially life-threatening diseases. A significant proportion of these patients
      develops progressive liver injury leading to cirrhosis and hepatocellular
      carcinoma. Unrecognized NAFLD constitutes a substantial proportion of patients
      with cryptogenic cirrhosis. Several large community-based studies have found
      increased mortality in NAFLD patients compared to the expected mortality of the
      general population of the same age and sex. Cardiovascular disease is an
      important cause of morbidity and mortality in patients with NAFLD and accounts
      for up to 30 % of overall death. Cardiovascular mortality does not seem to differ
      between simple steatosis and non-alcoholic steatohepatitis. NAFLD is associated
      with increased risk of both hepatic and extra-hepatic malignancy. Malignancy is
      among the most important causes of death in NAFLD patients. NAFLD is a risk
      factor for liver cancer even without cirrhosis. The steatotic liver has poor
      ability to regenerate after volume loss, which may lead to the development of
      liver failure and increased mortality after extended liver resection. Also,
      transplantation of steatotic liver results in an increased rate of poor graft
      function, primary graft non-function, and poorer outcome. There is a high
      recurrence rate of fatty liver disease in patients transplanted for NASH. 

PMID- 26202294
TI  - An integrated view of liver injury and disease progression in nonalcoholic
      steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common
      cause of chronic liver disease globally. NAFLD represents a host of
      pathophysiologic mechanisms that culminate in the accumulation of fat, in a
      predominantly macrovesicular pattern, in the liver along with varying degrees of
      inflammation, hepatocellular injury, apoptosis and fibrosis. The most common
      mechanism for the development of NAFLD is insulin resistance. Insulin resistance
      is commonly associated with obesity, although it can develop in individuals who
      do not have obesity. A consequence of insulin resistance is increased peripheral
      lipolysis and increased delivery of free fatty acids to the liver. The concept of
      lipotoxicity emerged as the mechanisms by which fatty acids produce cell injury,
      promote apoptosis and activate inflammatory pathways were elucidated. While much
      work has been done mainly in cell culture models, the free fatty acid
      concentration in the liver is not significantly changed in NAFLD. Recently, the
      focus has shifted to alterations in other lipid metabolic pathways that appear to
      play an important role in the genesis of nonalcoholic steatohepatitis, the
      aggressive form of NAFLD. The innate immune system and the intestinal microbiota
      have been implicated in the development of NAFLD. These mechanisms are reviewed
      in this article. 

PMID- 26202295
TI  - Lean NASH: distinctiveness and clinical implication.
AB  - INTRODUCTION: Non-alcoholic fatty liver (NAFL) in the absence of overweight
      and/or obesity, defined by the anthropometric parameter, body mass index (BMI),
      has been designated as 'lean NASH.' While maintaining a close pathophysiological
      link with metabolic syndrome (MS) and insulin resistance (IR), the presence of
      subtle alterations in measures of total body and regional adiposity not exceeding
      the designed cut-offs, are hallmarks of 'lean NASH.' MATERIAL AND METHODS:
      Available literature related to non-alcoholic steatohepatitis (NASH) in lean or
      non-obese individuals and its pathogenesis in general published in English
      language journals till the time of manuscript preparation were reviewed and
      critically analysed. ANALYSIS: Being a closely related but variant phenotype of
      NASH, its features metabolically resemble the well-characterized entity
      'metabolically obese normal weight (MONW)' individuals. Apart from total body
      adiposity, distribution of fat in different body compartments has assumed greater
      pathophysiologic relevance in characterizing 'lean NASH'. Detection of NASH in
      stringently defined non-obese individuals, by both BMI and waist circumference
      indices, indicates existence of a subset of NASH in which fat
      compartmentalization at ectopic sites is not picked up by the anthropometric
      yardsticks used. Volume [Quantity] and biological behavior of the visceral and
      deep subcutaneous adipose tissues contribute to this variant of NASH in non-obese
      subjects. Genetic predisposition to IR and MS along with the environmental
      influences like childhood nutritional status, dietary composition and gut
      microbiome possibly play pathogenetic role. CONCLUSION: The most important
      concern is in the principles of nomenclature within syndromes where clinical
      dissimilarities exist despite biological similarities. Till a uniformly
      acceptable pathophysiological and/or etiology-based classification emerges, the
      term "lean NASH" would continue to provide us an opportunity to ponder over and
      refine this subset of fatty liver in non-obese people and potentially significant
      liver disease.

PMID- 26202296
TI  - Insulin resistance: mechanism and implications for carcinogenesis and
      hepatocellular carcinoma in NASH.
AB  - INTRODUCTION: The effects of insulin resistance in human diseases are of
      paramount importance. Since the original proposal by the WHO indicating insulin
      resistance as the common substrate of the metabolic syndrome, large data are now
      available on its significance in cardiovascular diseases, nonalcoholic fatty
      liver disease and cancer risk. MATERIALS AND METHODS: We reviewed the evidence
      linking hyperinsulinemia to insulin resistance and ultimately to increased cancer
      risk. Insulin resistance, by reducing substrate flux along the PI3-K pathway, is
      followed by compensatory hyperinsulinemia, considered a potential stimulus for
      cancerogenesis along the MAP-K pathway. Adaptive mechanisms of fat storage,
      promoted by insulin resistance, chronically maintained in an obesiogenic
      environment, may lead to oxidative stress and inflammation and modify the immune
      responses, further increasing the carcinogenic potential. The increased cancer
      risk associated with obesity, type 2 diabetes and nonalcoholic fatty liver may
      thus be fueled by hyperinsulinemia. Insulin secretagogs and insulin treatment, by
      raising circulating insulin levels, further increase cancer risk, whereas insulin
      sensitizers are associated with decreased cancer risk (all sites) and
      specifically decrease hepatocellular carcinoma. Likewise, drugs related to the
      incretin system, which are weight neutral or even reduce whole-body and hepatic
      fat, improve insulin sensitivity and potentially reduce the cancer risk.
      CONCLUSION: New diabetes treatments might thus help decrease the future burden of
      diabetes-associated cancer and particularly of hepatocellular carcinoma.

PMID- 26202297
TI  - Non-alcoholic fatty liver disease-related hepatocellular carcinoma: a sleeping
      tiger in the Asia Pacific.
AB  - The epidemiology of hepatocellular carcinoma (HCC) in the Asia Pacific will
      undergo significant change over the next few decades as the prevalence of viral
      hepatitis declines and the burden of metabolic diseases increases. As the Asia
      Pacific embraces continued affluence, obesity and diabetes rates are burgeoning,
      becoming increasingly important to the incidence of HCC. Obesity and diabetes are
      established risk factors for HCC, either as substrates for non-alcoholic fatty
      liver disease (NAFLD) or as independent carcinogens themselves. This review
      summarises the epidemiological data on changing HCC trends in the Asia Pacific,
      particularly as it pertains to the emerging problem of NAFLD-related HCC. 

PMID- 26202298
TI  - Pharmacological agents for nonalcoholic steatohepatitis.
AB  - The rationale for specific pharmacologic therapy in nonalcoholic steatohepatitis
      (NASH) is determined by the potential for disease progression and the
      difficulties, in many patients, to successfully implement diet and lifestyle
      changes in the long term. Because they correct insulin resistance, insulin
      sensitizing agents are attractive candidates for the treatment of NASH. However,
      two randomized studies have shown that vitamin E, despite having no effect on
      insulin sensitivity, achieves interesting histological and biochemical efficacy.
      This review provides an insight into the therapeutic efficacy and safety issues
      of different pharmacological agents tested in human NASH. 

PMID- 26202301
TI  - Correction.

PMID- 26202300
TI  - HMGB1 binds to activated platelets via the receptor for advanced glycation end
      products and is present in platelet rich human coronary artery thrombi.
AB  - High mobility group box 1 (HMGB1) acts as both a nuclear protein that regulates
      gene expression, as well as a pro-inflammatory alarmin that is released from
      necrotic or activated cells. Recently, HMGB1-expression in human atherosclerotic
      plaques was identified. Therapeutic blockade of HMGB1 reduced the development of
      diet-induced atherosclerosis in ApoE knockout mice. Thus, we hypothesised an
      interaction between HMGB1 and activated platelets. Binding of recombinant HMGB1
      to platelets was assessed by flow cytometry. HMGB1 bound to thrombin-activated
      human platelets (MFI 2.49 vs 25.01, p=0.0079). Blood from wild-type, TLR4 and
      RAGE knockout mice was used to determine potential HMGB1 receptors on platelets.
      HMGB1 bound to platelets from wild type C57Bl6 (MFI 2.64 vs 20.3, p< 0.05), and
      TLR4-/- mice (MFI 2.11 vs 25.65, p< 0.05) but failed to show binding to platelets
      from RAGE-/- mice (p > 0.05). RAGE expression on human platelets was detected by
      RT-PCR with mRNA extracted from highly purified platelets and confirmed by
      Western blot and immunofluorescence microscopy. Platelet activation increased
      RAGE surface expression (MFI 4.85 vs 6.74, p< 0.05). Expression of HMGB1 in human
      coronary artery thrombi was demonstrated by immunohistochemistry and revealed
      high expression levels. Platelets bind HMGB1 upon thrombin-induced activation.
      Platelet specific expression of RAGE could be detected at the mRNA and protein
      level and is involved in the binding of HMGB1. Furthermore, platelet activation
      up-regulates platelet surface expression of RAGE. HMGB1 is highly expressed in
      platelet-rich human coronary artery thrombi pointing towards a central role for
      HMGB1 in atherothrombosis, thereby suggesting the possibility of platelet
      targeted anti-inflammatory therapies for atherothrombosis. 

PMID- 26202299
TI  - Blockade of Wnt/beta-catenin signaling suppresses breast cancer metastasis by
      inhibiting CSC-like phenotype.
AB  - The identification of cancer stem cells (CSCs) represents an important milestone
      in the understanding of chemodrug resistance and cancer recurrence. More
      specifically, some studies have suggested that potential metastasis-initiating
      cells (MICs) might be present within small CSC populations. The targeting and
      eradication of these cells represents a potential strategy for significantly
      improving clinical outcomes. A number of studies have suggested that
      dysregulation of Wnt/beta-catenin signaling occurs in human breast cancer.
      Consistent with these findings, our previous data have shown that the relative
      level of Wnt/beta-catenin signaling activity in breast cancer stem cells (BCSCs)
      is significantly higher than that in bulk cancer cells. These results suggest
      that BCSCs could be sensitive to therapeutic approaches targeting Wnt/beta
      catenin signaling pathway. In this context, abnormal Wnt/beta-catenin signaling
      activity may be an important clinical feature of breast cancer and a predictor of
      poor survival. We therefore hypothesized that Wnt/beta-catenin signaling might
      regulate self-renewal and CSC migration, thereby enabling metastasis and systemic
      tumor dissemination in breast cancer. Here, we investigated the effects of
      inhibiting Wnt/beta-catenin signaling on cancer cell migratory potential by
      examining the expression of CSC-related genes, and we examined how this pathway
      links metastatic potential with tumor formation in vitro and in vivo. 

PMID- 26202302
TI  - Exploring the oral health experiences of homeless people: a deconstruction
      reconstruction formulation.
AB  - OBJECTIVE: To explore qualitatively, using a grounded theory approach, homeless
      people's awareness of their oral health needs and how they access dental services
      using a deconstruction-reconstruction formulation, and provide recommendations
      for service designers and dental professionals who work with people experiencing
      homelessness. METHODS: A qualitative study using grounded theory methodology was
      conducted. A purposive sample of homeless people was recruited from health
      facilities and organizations serving homeless populations in four Scottish cities
      and towns. Participants were interviewed about their oral health within the wider
      context of their experiences of homelessness. Initial research questions were
      open and focused on social processes such as oral health practices and
      interaction with dental services. Data collection and analysis were carried out
      simultaneously and iteratively, with emerging findings informing subsequent
      cycles. Data analysis was guided by Glaser and Strauss's grounded theory
      methodology and involved constant comparison, coding of transcripts and detailed
      memo-writing. RESULTS: Thirty-four homeless people took part. Participant
      experiences were conceptualized as a journey into and through the stages of
      homelessness, towards 'reclaiming life'. Oral health experiences were mapped as a
      parallel 3-stage journey from the deconstruction of self-care, to the
      construction and maintenance of the neglected dentine, and finally to the
      reclamation of oral health resulting in a reconstructed functioning dentition.
      CONCLUSIONS: This qualitative exploration using a deconstruction-reconstruction
      formulation has added to the understanding of homeless people's oral health
      awareness and dental treatment access while permitting an examination of the
      wider socioeconomic and psychosocial issues that disrupt their intentions to
      attend for treatment. These findings provide service designers and dental
      professionals with recommendations for the provision of responsive, acceptable
      and appropriate dental health services for those experiencing homelessness.

PMID- 26202303
TI  - Isolation and purification of rabbit mesenchymal stem cells using an optimized
      protocol.
AB  - Mesenchymal stem cells were first isolated and grown in vitro by Friedenstein
      over 40 yr ago; however, their isolation remains challenging as they lack unique
      markers for identification and are present in very small quantities in
      mesenchymal tissues and bone marrow. Using whole marrow samples, common methods
      for mesenchymal stem cell isolation are the adhesion method and density gradient
      fractionation. The whole marrow sample adhesion method still results in the
      nonspecific isolation of mononuclear cells, and activation and/or potential loss
      of target cells. Density gradient fractionation methods are complicated, and may
      result in contamination with toxic substances that affect cell viability. In the
      present study, we developed an optimized protocol for the isolation and
      purification of mesenchymal stem cells based on the principles of hypotonic lysis
      and natural sedimentation. 

PMID- 26202304
TI  - Linking Family Economic Hardship to Early Childhood Health: An Investigation of
      Mediating Pathways.
AB  - OBJECTIVES: The underlying mechanisms through which family economic adversity
      influences child health are less understood. Taking a process-oriented approach,
      this study examined maternal mental health and investment in children, child
      health insurance, and child healthcare as mediators linking family economic
      hardship (FEH) to child health. METHODS: A structural equation modeling was
      applied to test the hypothesized mediating model. RESULTS: After adjustment for
      sociodemographic risk factors, results revealed: (1) a significant direct path
      linking FEH to poor child health (effect size = .372), and (2) six significant
      mediating pathways (total effect size = .089). In two mediating pathways,
      exposures to FEH undermined mothers' mental health: in the first pathway poor
      maternal mental health led to decreased parental investment, which, in turn,
      contributed to poor child health, whereas in the second pathway the adverse
      effect of poor maternal mental health was cascaded through child unmet healthcare
      need, which resulted in poor child health. One pathway involved child insurance
      status, where the effect of FEH increased the likelihood to be uninsured, which
      led to unmet healthcare need, and, in turn, to poor health. Three pathways
      involved preventive care: in one pathway FEH contributed to poor preventive care,
      which led to unmet healthcare need and then to poor health; in the other two
      pathways where poor preventive care respectively gave rise to decreased
      investment in children or poor maternal mental health, which further contributed
      to poor child health. CONCLUSIONS: Results suggest that the association between
      FEH and children's health is mediated by multiple pathways.

PMID- 26202306
TI  - Toxic effects of nitenpyram on antioxidant enzyme system and DNA in zebrafish
      (Danio rerio) livers.
AB  - Nitenpyram is one of the most commonly used neonicotinoid pesticide worldwide and
      was found to be toxic to non-target aquatic organisms. Therefore, the purpose of
      this study was to investigate the oxidative stress, changes in the detoxifying
      system and DNA damage in zebrafish induced by nitenpyram. In the present study,
      zebrafish (Danio rerio) were exposed to four concentrations (0.6, 1.2, 2.5, and
      5.0 mg L(-1)) for 28 d and then sampled in triplicate on days 7, 14, 21 and 28.
      Superoxide dismutase (SOD) and catalase (CAT) activities were dramatically
      inhibited at most exposure times compared with the control group, except SOD at
      low concentration (0.6 mg L(-1)) of nitenpyram and CAT on day 21. This difference
      is due to the excess reactive oxygen species (ROS) produced and increased
      malondialdehyde (MDA) content in zebrafish livers. The activity of glutathione S
      transferase (GST) increased in in the treatment groups at a higher concentration
      compared with the control group. We found that nitenpyram exposure could affect
      the antioxidant enzymes and DNA damage in the exposed zebrafish livers.
      Additionally, the changes in the antioxidant enzyme activities could be an
      adaptive response protecting against the toxicity induced by nitenpyram.

PMID- 26202305
TI  - First prospective report on immune tolerance in poor risk haemophilia A inhibitor
      patients with a single factor VIII/von Willebrand factor concentrate in an
      observational immune tolerance induction study.
AB  - INTRODUCTION/BACKGROUND: Development of neutralizing inhibitors against factor
      VIII (FVIII) is a major complication of haemophilia A treatment. AIM: The
      ongoing, international, open-label, uncontrolled, observational immune tolerance
      induction (ObsITI) study evaluates ITI, the standard of care in patients with
      inhibitors. PATIENTS/METHODS: Forty-eight prospective patients in this interim
      analysis received a single plasma-derived, von Willebrand factor-stabilized,
      FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol,
      'low responders' at ITI start (<5 BU) received 50-100 IU FVIII kg(-1) daily, or
      every other day; 'high responders' (>=5 BU) received 100 IU FVIII kg(-1) every 12
      h. RESULTS: Forty of 48 patients (83.3%), had at least one risk factor for poor
      ITI-prognosis at ITI start (i.e. age >=7 years, >2 years since inhibitor
      diagnosis, inhibitor titre >=10 BU at the start of ITI, or prior ITI failure).
      Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial
      success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with
      poor prognosis factors. All six low responders achieved complete success. ITI
      outcome was significantly associated with inhibitor titre level at ITI start (P =
      0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly
      bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P =
      0.0007). Twenty-two of 35 high responder patients (62.9%) with >=1 poor prognosis
      factor achieved complete success. CONCLUSION: Treatment with a single pdFVIII/VWF
      concentrate, mainly according to the Bonn protocol, resulted in a high ITI
      success rate in haemophilia A patients with inhibitors and poor prognosis for ITI
      success.

PMID- 26202308
TI  - Increased frequency of rhabdomyolysis in familial dysautonomia.
AB  - INTRODUCTION: Familial dysautonomia (FD; OMIM # 223900) is an autosomal recessive
      disease with features of impaired pain and temperature perception and lack of
      functional muscle spindles. After 3 FD patients presented with rhabdomyolysis in
      a short time span, we aimed to determine the frequency of rhabdomyolysis is this
      population. METHODS: This study was a retrospective chart review of 665 FD
      patients. RESULTS: Eight patients had at least 1 episode of rhabdomyolysis. Two
      patients had 2 episodes. The average incidence of rhabdomyolysis in FD was 7.5
      per 10,000 person-years. By comparison, the average incidence with statins has
      been reported to be 0.44 per 10,000 person-years. Mean maximum creatine kinase
      (CK) level was 32,714 +/- 64,749 U/L. Three patients had hip magnetic resonance
      imaging showing gluteal hyperintensities. CONCLUSIONS: Patients with FD have an
      increased incidence of rhabdomyolysis. We hypothesize that this may result from a
      combination of absent functional muscle spindles and muscle mitochondrial
      abnormalities.

PMID- 26202309
TI  - Vitamin D attenuates proteinuria by inhibition of heparanase expression in the
      podocyte.
AB  - The glomerular filtration barrier consists of podocytes, the glomerular basement
      membrane, and endothelial cells covered with a glycocalyx. Heparan sulphate (HS)
      in the glomerular filtration barrier is reduced in patients with proteinuria,
      which is associated with increased expression of the HS-degrading enzyme
      heparanase. Previously, we showed that heparanase is essential for the
      development of proteinuria in experimental diabetic nephropathy. Vitamin D
      supplementation reduces podocyte loss and proteinuria in vitro and in vivo.
      Therefore, we hypothesize that vitamin D reduces proteinuria by reducing
      glomerular heparanase. Adriamycin-exposed rats developed proteinuria and showed
      increased heparanase expression, which was reduced by 1,25-dihydroxyvitamin D3
      (1,25-D3) treatment. In vitro, adriamycin increased heparanase mRNA in the
      podocyte, which could be corrected by 1,25-D3 treatment. In addition, 1,25-D3
      treatment reduced transendothelial albumin passage after adriamycin stimulation.
      In line with these results, we showed direct binding of the vitamin D receptor to
      the heparanase promoter, and 1,25-D3 dose-dependently reduced heparanase promoter
      activity. Finally, 1,25-D3-deficient 25-hydroxy-1alpha-hydroxylase knockout mice
      developed proteinuria and showed increased heparanase, which was normalized by
      1,25-D3 treatment. Our data suggest that the protective effect of vitamin D on
      the development of proteinuria is mediated by inhibiting heparanase expression in
      the podocyte.

PMID- 26202310
TI  - Complexity of Compensatory Effects in Nrf1 Knockdown: Linking Undeveloped Anxiety
      Like Behavior to Prevented Mitochondrial Dysfunction and Oxidative Stress.
AB  - Anxiety-related disorders are complex illnesses that underlying molecular
      mechanisms need to be understood. Mitochondria stand as an important link between
      energy metabolism, oxidative stress, and anxiety. The nuclear factor, erythroid
      derived 2,-like 1(Nrf1) is a member of the cap "n" collar subfamily of basic
      region leucine zipper transcription factors and plays the major role in
      regulating the adaptive response to oxidants and electrophiles within the cell.
      Here, we injected small interfering RNA (siRNA) targeting Nrf1 in dorsal third
      ventricle of adult male albino Wistar rats and subsequently examined the effect
      of this silencing on anxiety-related behavior. We also evaluated apoptotic
      markers and mitochondrial biogenesis factors, along with electron transport chain
      activity in three brain regions: hippocampus, amygdala, and prefrontal cortex.
      Our data revealed that in the group that received Nrf1-siRNA, anxiety-related
      behavior did not show any significant changes compared to the control group.
      Caspase-3 did not increase in Nrf1-siRNA-injected rats even though Bax/Bcl2 ratio
      markedly elevated in Nrf1-knockdown rats in all three mentioned regions compared
      to control rats. Also, Nrf1 silencing of complex I and II-III did not alter,
      generally. In addition, Nrf1-knockdown affected mitochondrial biogenesis markers.
      The level of peroxisome proliferator-activated receptor gamma coactivator-1alpha
      and cytochrome-c increased, which indicates a possible role for mitochondrial
      biogenesis in anxiety. 

PMID- 26202312
TI  - Toxic colonoscopy--how investigating active inflammatory bowel disease can lead
      to the serious complication of toxic megacolon.

PMID- 26202311
TI  - Downregulation of cancer stem cell properties via mTOR signaling pathway
      inhibition by rapamycin in nasopharyngeal carcinoma.
AB  - Rapamycin, a mammalian target of rapamycin (mTOR) signaling inhibitor, inhibits
      cancer cell proliferation and tumor formation, including in nasopharyngeal
      carcinoma (NPC), which we proved in a previous study. However, whether rapamycin
      affects cancer stem cells (CSCs) is unclear. In examining samples of NPCs, we
      found regions of CD44-positive cancer cells co-expressing the stem cell biomarker
      OCT4, suggesting the presence of CSCs. Following this, we used double-label
      immunohistochemistry to identify whether the mTOR signaling pathway was activated
      in CD44-positive CSCs in NPCs. We used a CCK-8 assay and western blotting to
      explore whether the stem cell biomarkers CD44 and SOX2 and the invasion protein
      MMP-2 could be suppressed by treatment with rapamycin in cultured primary NPC
      cells and secondary tumors in BALB/c nude mice. Interestingly, we found that
      rapamycin inhibited mTOR signaling in addition to simultaneously downregulating
      the expression of CD44, SOX2 and MMP-2 and that it affected cell growth and tumor
      size and weight both in vitro and in vivo. Collectively, we confirmed for the
      first time that CSC properties are reduced and invasion potential is restrained
      in response to mTOR signaling inhibition in NPC. This evidence indicates that the
      targeted inhibition of CSC properties may provide a novel strategy to treat
      cancer. 

PMID- 26202313
TI  - An infectious cause of acute kidney injury with low serum potassium.
AB  - A 67-year-old man was referred to our hospital because of acute kidney injury,
      thrombocytopenia and hyperbilirubinemia. Despite severe kidney failure,
      hypokalemia was present. One infectious cause explained the whole clinical
      picture. 

PMID- 26202314
TI  - Acute spinal cord compression: a rare complication of dual antiplatelet therapy.
AB  - A 73-year-old woman presented with acute shortness of breath and exacerbation of
      chronic back pain. She was diagnosed with pulmonary oedema and a non-ST-elevation
      myocardial infarction following chest X-ray, ECG and high sensitivity troponin
      levels. She subsequently underwent coronary angioplasty with deployment of drug
      eluting stents to her circumflex and left anterior descending arteries and was
      started on aspirin and clopidogrel for her dual antiplatelet therapy.
      Unfortunately, following the procedure, she gradually lost power and sensation in
      both lower limbs. MRI of her spine confirmed an extradural haematoma causing
      thoracic cord compression. She was managed conservatively following discussions
      with neurosurgeons and developed further complications secondary to her
      immobility. 

PMID- 26202315
TI  - Maintaining sharp focus on a grainy film: miliary pattern in an elderly woman
      with acute respiratory failure.
AB  - An elderly woman with a history of pulmonary tuberculosis reportedly diagnosed
      and treated 30 years prior to presentation was found unresponsive at home. Chest
      imaging revealed innumerable pulmonary nodules worrisome for an infectious
      process, specifically tuberculosis. The patient deteriorated rapidly and in
      accordance with her wishes, aggressive interventions were withheld. She died
      within 48 h from respiratory failure. A limited chest autopsy was performed and
      revealed the cause of death as lymphangitic spread of cancer from a primary lung
      adenocarcinoma.

PMID- 26202316
TI  - Efficacy of intravenous immunoglobulins in a patient with systemic lupus
      erythematosus presenting with Stevens-Johnson syndrome.

PMID- 26202317
TI  - Female anorectal malformation in a woman.
AB  - Delayed presentation of patients with anorectal malformation is not uncommon,
      especially in developing countries. However, presentation beyond teenage years is
      not commonplace. We describe a case of a 28-year-old woman who presented for
      treatment due to marital issues. 

PMID- 26202318
TI  - Conservative management of gastric emphysema with hepatoportal venous gas.

PMID- 26202319
TI  - Levamisole-adulterated cocaine: a case of retiform purpura, cutaneous necrosis
      and neutropenia.

PMID- 26202320
TI  - Perceived effectiveness of text and pictorial health warnings for smokeless
      tobacco packages in Navi Mumbai, India, and Dhaka, Bangladesh: findings from an
      experimental study.
AB  - OBJECTIVE: To examine the perceived effectiveness of text and pictorial smokeless
      tobacco health warnings in India and Bangladesh, including different types of
      message content. METHODS: An experimental study was conducted in Navi Mumbai,
      India (n=1002), and Dhaka, Bangladesh (n=1081). Face-to-face interviews were
      conducted on tablets with adult (>=19 years) smokeless tobacco users and youth
      (16-18 years) users and non-users. Respondents viewed warnings depicting five
      health effects, within one of the four randomly assigned warning label conditions
      (or message themes): (1) text-only, (2) symbolic pictorial, (3) graphic pictorial
      or (4) personal testimonial pictorial messages. RESULTS: Text-only warnings were
      perceived as less effective than all of the pictorial styles (p<0.001 for all).
      Graphic warnings were given higher effectiveness ratings than symbolic or
      testimonial warnings (p<0.001). No differences were observed in levels of
      agreement with negative attitudes and beliefs across message themes, after
      respondents had viewed warnings. CONCLUSIONS: Pictorial warnings are more
      effective than text-only messages. Pictorial warnings depicting graphic health
      effects may have the greatest impact, consistent with research from high-income
      countries on cigarette warnings.

PMID- 26202321
TI  - Molecular identification of clinical Nocardia isolates from India.
AB  - The epidemiology of nocardiosis is evolving with increasing number of Nocardia
      spp. causing human infection. In recent years, molecular techniques have been
      used to identify Nocardia spp. There are limited data available on the spectrum
      of Nocardia spp. isolated from clinical samples in India. Here, a molecular study
      was carried on 30 clinical isolates maintained in our National Culture Collection
      to evaluate the techniques used for identifying the agents. The isolates were
      identified by sequencing two promising genes: the 16S rRNA gene and hsp65. Both
      hsp65 and the 16S rRNA gene could reliably identify 90 % of Nocardia isolates,
      i.e. N. farcinica, N. cyriacigeorgica, N. brasiliensis, N. otitidiscaviarum, N.
      amamiensis and N. pneumoniae. The mean percentage dissimilarity of sequence
      identification was higher using the hsp65 gene (4 %, range 0-7.9 %) compared with
      the 16S rRNA gene (2.3 %, range 0-8.9 %). Two isolates that showed ambiguous
      results in both the short segment of the 16S rRNA gene and hsp65 sequences could
      be resolved by sequencing a larger fragment (~1000 bp) of the 16S rRNA gene. Both
      of these isolates were identified as N. beijingensis with similarities of 99.8
      and 100 % compared with the standard strain. Genotyping of N. cyriacigeorgica
      strains was performed using hsp65 gene sequences and compared with previously
      described genotypes. Our N. cyriacigeorgica isolates belonged to genotype 1 (n =
      4) and genotype 2 (n = 2). The present study highlights a wide spectrum of
      Nocardia spp. in India and emphasizes the need for molecular techniques for
      identification to the species level. 

PMID- 26202322
TI  - Instrumented knee joint implants: innovations and promising concepts.
AB  - This article focuses on in vivo implementations of instrumented knee implants and
      recent prototypes with highly innovative potential. An in-depth analysis of the
      evolution of these systems was conducted, including three architectures developed
      by two research teams for in vivo operation that were implanted in 13 patients.
      The specifications of their various subsystems: sensor/transducers, power
      management, communication and processing/control units are presented, and their
      features are compared. These systems were designed to measure biomechanical
      quantities to further assist in rehabilitation and physical therapy, to access
      proper implant placement and joint function and to help predicting aseptic
      loosening. Five prototype systems that aim to improve their operation, as well as
      include new abilities, are also featured. They include technology to assist
      proper ligament tensioning and ensure self-powering. One can conclude that the
      concept of instrumented active knee implant seems the most promising trend for
      improving the outcomes of knee replacements. 

PMID- 26202323
TI  - Empirical model based on Weibull distribution describing the destruction kinetics
      of natural microbiota in pineapple (Ananas comosus L.) puree during high-pressure
      processing.
AB  - High pressure inactivation of natural microbiota viz. aerobic mesophiles (AM),
      psychrotrophs (PC), yeasts and molds (YM), total coliforms (TC) and lactic acid
      bacteria (LAB) in pineapple puree was studied within the experimental domain of
      0.1-600 MPa and 30-50  degrees C with a treatment time up to 20 min. A complete
      destruction of yeasts and molds was obtained at 500 MPa/50  degrees C/15 min;
      whereas no counts were detected for TC and LAB at 300 MPa/30  degrees C/15 min. A
      maximum of two log cycle reductions was obtained for YM during pulse
      pressurization at the severe process intensity of 600 MPa/50  degrees C/20 min.
      The Weibull model clearly described the non-linearity of the survival curves
      during the isobaric period. The tailing effect, as confirmed by the shape
      parameter (beta) of the survival curve, was obtained in case of YM (beta<1);
      whereas a shouldering effect (beta>1) was observed for the other microbial
      groups. Analogous to thermal death kinetics, the activation energy (Ea, kJ.mol(
      1)) and the activation volume (Va, mL.mol(-1)) values were computed further to
      describe the temperature and pressure dependencies of the scale parameter (delta,
      min), respectively. A higher delta value was obtained for each microbe at a lower
      temperature and it decreased with an increase in pressure. A secondary kinetic
      model was developed describing the inactivation rate (k, min(-1)) as a function
      of pressure (P, MPa) and temperature (T, K) including the dependencies of Ea and
      Va on P and T, respectively.

PMID- 26202324
TI  - Diversity of Saccharomyces cerevisiae strains isolated from Borassus akeassii
      palm wines from Burkina Faso in comparison to other African beverages.
AB  - In South-West of Burkina Faso, palm wine is produced by spontaneous fermentation
      of the sap from a specific palm tree Borassus akeassii and plays an important
      role in people's lives. Saccharomyces cerevisiae is the main agent of this
      alcoholic fermentation but little is known about the diversity of the isolates
      from palm. In this work, 39 Saccharomyces cerevisiae strains were isolated from
      palm wine samples collected from 14 sites in Burkina Faso, as well as 7 isolates
      obtained from sorghum beer (Dolo) from 3 distant sites. Their diversity was
      analyzed at 12 microsatellite loci, and compared to the genotypes obtained for
      other African yeast populations isolated from Cocoa hulks from Ghana, sorghum
      beer from Ivory Coast, palm wine from Djibouti Republic, and to our database of
      strains from miscellaneous origins (bread, beer, wine, sake, oaks...). The ploidy
      of these strains has been assessed as well by flow cytometry. Our results show
      that B. akeassii palm wine contains a specific yeast population of diploid
      strains, different from Dolo produced in the same area and from other palm wine
      strains from Ivory Coast, Nigeria, or Djibouti Republic. In contrast, Dolo
      strains appeared as a group of related and mainly tetraploid strains despite
      being isolated from different countries. 

PMID- 26202325
TI  - Robot-supported upper limb training in a virtual learning environment : a pilot
      randomized controlled trial in persons with MS.
AB  - BACKGROUND: Despite the functional impact of upper limb dysfunction in multiple
      sclerosis (MS), effects of intensive exercise programs and specifically robot
      supported training have been rarely investigated in persons with advanced MS.
      AIM: To investigate the effects of additional robot-supported upper limb training
      in persons with MS compared to conventional treatment only. METHODS: Seventeen
      persons with MS (pwMS) (median Expanded Disability Status Scale of 8, range 3.5
      8.5) were included in a pilot RCT comparing the effects of additional robot
      supported training to conventional treatment only. Additional training consisted
      of 3 weekly sessions of 30 min interacting with the HapticMaster robot within an
      individualised virtual learning environment (I-TRAVLE). Clinical measures at body
      function (Hand grip strength, Motricity Index, Fugl-Meyer) and activity (Action
      Research Arm test, Motor Activity Log) level were administered before and after
      an intervention period of 8 weeks. The intervention group were also evaluated on
      robot-mediated movement tasks in three dimensions, providing active range of
      motion, movement duration and speed and hand-path ratio as indication of movement
      efficiency in the spatial domain. Non-parametric statistics were applied.
      RESULTS: PwMS commented favourably on the robot-supported virtual learning
      environment and reported functional training effects in daily life. Movement
      tasks in three dimensions, measured with the robot, were performed in less time
      and for the transporting and reaching movement tasks more efficiently. There were
      however no significant changes for any clinical measure in neither intervention
      nor control group although observational analyses of the included cases indicated
      large improvements on the Fugl-Meyer in persons with more marked upper limb
      dysfunction. CONCLUSION: Robot-supported training lead to more efficient movement
      execution which was however, on group level, not reflected by significant changes
      on standard clinical tests. Persons with more marked upper limb dysfunction may
      benefit most from additional robot-supported training, but larger studies are
      needed. TRIAL REGISTRATION: This trial is registered within the registry Clinical
      Trials GOV ( NCT02257606 ).

PMID- 26202326
TI  - Instruments to measure patient experience of healthcare quality in hospitals: a
      systematic review.
AB  - BACKGROUND: Improving and sustaining the quality of hospital care is an
      international challenge. Patient experience data can be used to target
      improvement and research. However, the use of patient experience data has been
      hindered by confusion over multiple instruments (questionnaires) with unknown
      psychometric testing and utility. METHODS: We conducted a systematic review and
      utility critique of questionnaires to measure patient experience of healthcare
      quality in hospitals. Databases (Medical Literature Analysis and Retrieval System
      (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL),
      Psychological Information (PsychINFO) and Web of Knowledge until end of November
      2013) and grey literature were scrutinised. Inclusion criteria were applied to
      all records with a 10 % sample independently checked. Critique included (1)
      application of COSMIN checklists to assess the quality of each psychometric
      study, (2) critique of psychometric results of each study using Terwee et al.
      criteria and (3) development and critique of additional aspects of utility for
      each instrument. Two independent reviewers completed each critique. Synthesis
      included combining findings in a utility matrix. RESULTS: We obtained 1157
      records. Of these, 26 papers measuring patient experience of hospital quality of
      care were identified examining 11 international instruments. We found evidence of
      extensive theoretical/development work. The quality of methods and results was
      variable but mostly of a high standard. Additional aspects of utility found that
      (1) cost efficiency was mostly poor, due to the resource necessary to obtain
      reliable samples; (2) acceptability of most instruments was good and (3)
      educational impact was variable, with evidence on the ease of use, for
      approximately half of the questionnaires. CONCLUSIONS: Selecting the right
      patient experience instrument depends on a balanced consideration of aspects of
      utility, aided by the matrix. Data required for high stakes purposes requires a
      high degree of reliability and validity, while those used for quality improvement
      may tolerate lower levels of reliability in favour of other aspects of utility
      (educational impact, cost and acceptability). SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42013006754.

PMID- 26202327
TI  - Broad autism phenotype features of Chinese parents with autistic children and
      their associations with severity of social impairment in probands.
AB  - BACKGROUND: Parents of children with autism have higher rates of broad autism
      phenotype (BAP) features than parents of typically developing children (TDC) in
      Western countries. This study was designed to examine the rate of BAP features in
      parents of children with autism and the relationship between parental BAP and the
      social impairment of their children in a Chinese sample. METHODS: A total of 299
      families with autistic children and 274 families with TDC participated in this
      study. Parents were assessed using the Broad Autism Phenotype Questionnaire
      (BAPQ), which includes self-report, informant-report, and best-estimate versions.
      Children were assessed using the Chinese version of the Social Responsiveness
      Scale (SRS). RESULTS: Parents of children with autism were significantly more
      likely to have BAP features than were parents of TDC; mothers and fathers in
      families with autistic children had various BAP features. The total scores of the
      informant and best-estimate BAPQ versions for fathers were significantly
      associated with their children's SRS total scores in the autism group, whereas
      the total scores of the three BAPQ versions for mothers were significantly
      associated with their children's SRS total scores in the TDC group. In the autism
      group, the total SRS scores of children with "BAP present" parents (informant and
      best-estimate) were higher than the total SRS scores of children with"BAP absent"
      parents. In the TDC group, the total SRS scores of children with "BAP present"
      parents were higher than the total SRS scores of children with"BAP absent"
      parents (best-estimate). CONCLUSIONS: Parents of autistic children were found to
      have higher rates of BAP than parents of TDC in a sample of Chinese parents. The
      BAP features of parents are associated with their children's social functioning
      in both autism families and TDC families, but the patterns of the associations
      are different.

PMID- 26202328
TI  - Comparative proteomics analysis provide novel insight into laminitis in Chinese
      Holstein cows.
AB  - BACKGROUND: Laminitis is considered as the most important cause of hoof lameness
      in dairy cows, which causes abundant economic losses in husbandry. Through
      intense efforts in past decades, the etiology of laminitis is preliminarily
      considered to be subacute ruminal acidosis; however, the pathogenesis of
      laminitis needs further research. The differentially expressed proteins (DEP)
      were detected in plasma of healthy cows and clinical laminitis cows by two
      dimensional gel electrophoresis (2-DE) and identified by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. RESULTS: Nineteen protein
      spots were differentially expressed, and 16 kinds of proteins were identified
      after peptide mass fingerprint search and bioinformatics analysis. Of these, 12
      proteins were differentially up-regulated and 4 down-regulated. Overall, these
      differential proteins were involved in carbohydrate metabolism, lipids
      metabolism, molecular transport, immune regulation, inflammatory response,
      oxidative stress and so on. CONCLUSIONS: The DEPs were closely related to the
      occurrence and development of laminitis and the lipid metabolic disturbance may
      be a new pathway to cause laminitis in dairy cows. The results provide the theory
      foundation for further revealing the mechanism of laminitis and screening the
      early diagnostic proteins and therapeutic target.

PMID- 26202329
TI  - Is there an association of vitamin B12 status with neurological function in older
      people? A systematic review.
AB  - Low vitamin B12 status is common in older people; however, its public health
      significance in terms of neurological manifestations remains unclear. The present
      systematic review evaluated the association of vitamin B12 status with
      neurological function and clinically relevant neurological outcomes in adults
      aged 50+ years. A systematic search of nine bibliographic databases (up to March
      2013) identified twelve published articles describing two longitudinal and ten
      cross-sectional analyses. The included study populations ranged in size (n 28
      2287) and mean/median age (range 65-81 years). Studies reported various
      neurological outcomes: nerve function; clinically measured signs and symptoms of
      nerve function; self-reported neurological symptoms. Studies were assessed for
      risk of bias, and results were synthesised qualitatively. Among the general
      population groups of older people, one longitudinal study reported no
      association, and four of seven cross-sectional studies reported limited evidence
      of an association of vitamin B12 status with some, but not all, neurological
      outcomes. Among groups with clinical and/or biochemical evidence of low vitamin
      B12 status, one longitudinal study reported an association of vitamin B12 status
      with some, but not all, neurological outcomes and three cross-sectional analyses
      reported no association. Overall, there is limited evidence from observational
      studies to suggest an association of vitamin B12 status with neurological
      function in older people. The heterogeneity and quality of the evidence base
      preclude more definitive conclusions, and further high-quality research is needed
      to better inform understanding of public health significance in terms of
      neurological function of vitamin B12 status in older people.

PMID- 26202331
TI  - Highly Diastereo- and Enantioselective Michael Addition of Nitroalkanes to 2
      Enoyl-Pyridine N-Oxides Catalyzed by Scandium(III)/Copper(II) Complexes.
AB  - A C2 -symmetric Schiff-base ligand, derived from tridentate-Schiff-base, was
      developed and successfully applied to the asymmetric Michael addition of
      nitroalkanes to 2-enoyl-pyridine N-oxides. With this newly catalytic system, an
      unprecedented diastereoselectivity was obtained in the asymmetric Michael
      addition of nitroalkanes to 2-enoyl-pyridine N-oxides. In addition, a switch in
      enantioselectivity was achieved by using this newly catalytic system and our
      previous catalyst. After a facile reduction, the optically active adduct was
      converted to a biologically active dihydro-2H-pyrrol 4 a. Furthermore, a
      connection of two tridentate-Schiff-base subunits proved to be an effective
      strategy in ligand design.

PMID- 26202332
TI  - Unplanned reoperations after microvascular free tissue transfer: An analysis of
      2,244 patients using the american college of surgeons national surgical quality
      improvement program database.
AB  - PURPOSE: Our intent was to evaluate unplanned reoperations as a quality indicator
      for microvascular free tissue transfer (MFTT). METHODS: The National Surgical
      Quality Improvement Program database was used to identify MFTT cases from January
      2012 to December 2013. Multivariate logistic regression models were used to
      determine risk factors for unplanned reoperations. RESULTS: We identified 2,244
      MFTT cases. There were 290 associated unplanned reoperations (12.92%). There was
      a threefold increase in the rate of complications when patients underwent
      reoperation (58.28% vs 18.12%, p < 0.0001). Head and neck reconstructions had the
      highest rate of reoperations (18.04%). Most reoperations were debridements
      (38.28%), followed by microvascular procedures (28.97%) and flap revisions
      (26.55%). American Society of Anesthesiologist (ASA) classification >=3 [OR
      1.565, 95% CI (1.204, 2.034), p = 0.0008] and prolonged operative time [OR 1.597,
      95% CI (1.221, 2.089), p = 0.0006] were significant independent risk factors for
      reoperations. CONCLUSIONS: Unplanned reoperations are a useful quality indicator
      for MFTT. ASA classification >=3 and prolonged operative time were risk factors
      associated with an increased risk for unplanned reoperations. (c) 2015 Wiley
      Periodicals, Inc. Microsurgery 37:184-189, 2017.

PMID- 26202333
TI  - Prevalence of Obesity in Patients with Psoriasis: Results of the National Study
      PsoHealth3.
AB  - BACKGROUND: Psoriasis is frequently associated with obesity which possibly
      contributes to reduced treatment response. OBJECTIVES: Assessment of the
      prevalence of obesity in patients with psoriasis in Germany 2013/2014. PATIENTS
      AND METHODS: The frequency of overweight and obesity was assessed by the body
      mass index (BMI) and evaluated according to the severity of psoriasis [Psoriasis
      Area and Severity Index (PASI)]. RESULTS: This national, cross-sectional survey
      involved 83 dermatological practices and outpatient clinics, including 1,265
      patients (mean age 52 years; 43.4% female). The BMI of patients with psoriasis in
      2013/2014 was found to be 28.0 and therefore was significantly higher compared to
      that of patients with psoriasis in 2007 with a BMI of 26.9 as well as compared to
      the normal population in 2013 with an overall BMI of 25.9. CONCLUSIONS: The
      prevalence of obesity in patients with psoriasis is higher than in the normal
      population. The trend towards a higher BMI in patients with psoriasis continues
      over time.

PMID- 26202330
TI  - Nutritional systems biology of type 2 diabetes.
AB  - Type 2 diabetes (T2D) has become an increasingly challenging health burden due to
      its high morbidity, mortality, and heightened prevalence worldwide. Although
      dietary and nutritional imbalances have long been recognized as key risk factors
      for T2D, the underlying mechanisms remain unclear. The advent of nutritional
      systems biology, a field that aims to elucidate the interactions between dietary
      nutrients and endogenous molecular entities in disease-related tissues, offers
      unique opportunities to unravel the complex mechanisms underlying the health
      modifying capacities of nutritional molecules. The recent revolutionary advances
      in omics technologies have particularly empowered this incipient field. In this
      review, we discuss the applications of multi-omics approaches toward a systems
      level understanding of how dietary patterns and particular nutrients modulate the
      risk of T2D. We focus on nutritional studies utilizing transcriptomics,
      epigenomomics, proteomics, metabolomics, and microbiomics, and integration of
      diverse omics technologies. We also summarize the potential molecular mechanisms
      through which nutritional imbalances contribute to T2D pathogenesis based on
      these studies. Finally, we discuss the remaining challenges of nutritional
      systems biology and how the field can be optimized to further our understanding
      of T2D and guide disease management via nutritional interventions. 

PMID- 26202334
TI  - Progressive Multiple Cavernous Angiomas after Radiotherapy in a Pediatric Patient
      with Medulloblastoma: A Case Report.
AB  - BACKGROUND: We report a case of progressive multiple cavernous angiomas. PATIENT
      AND METHOD: A 16-year-old boy presented with a 2-month history of headache and
      dizziness. Six years earlier, he underwent surgery for cerebellar medulloblastoma
      and subsequent chemoradiotherapy according to the M-051 protocol of the Korean
      Society of Pediatric Neuro-Oncology. Follow-up brain magnetic resonance imaging
      (MRI) revealed a tiny hemorrhage on the cerebellum 3 months after 23.4-Gy
      craniospinal and 32.4-Gy boost radiotherapy. RESULT: The multiple hemorrhagic
      lesions had progressively developed on the whole brain without any symptoms for 6
      years. On admission, MRI revealed a 1.5-cm enlarged mass with subacute hemorrhage
      on the right frontal area. The mass was totally removed and diagnosed as
      cavernous angioma. However, 5 months later, the patient complained of a headache.
      MRI revealed 1.4- and 0.7-cm enlarged masses on the left frontal and right
      temporal areas with internal hemorrhage, respectively. The left frontal mass was
      totally removed, and the histopathological finding was suggestive of cavernous
      angioma. CONCLUSION: This case showed early-developed multiple hemorrhagic
      lesions after radiotherapy, which had been progressive and were associated with
      some symptomatic cavernous angiomas. Pediatric patients with brain radiotherapy
      should undergo radiological check-up to identify vascular lesions, especially
      symptomatic patients.

PMID- 26202336
TI  - Benchmarking Continuum Solvent Models for Keto-Enol Tautomerizations.
AB  - Experimental free energies of tautomerization, DeltaGT, were used to benchmark
      the gas-phase predictions of 17 different quantum mechanical methods and eight
      basis sets for seven keto-enol tautomer pairs dominated by their enolic form. The
      G4 method and M06/6-31+G(d,p) yielded the most accurate results, with mean
      absolute errors (MAE's) of 0.95 and 0.71 kcal/mol, respectively. Using these two
      theory levels, the solution-phase DeltaGT values for 23 unique tautomer pairs
      composed of aliphatic ketones, beta-dicarbonyls, and heterocycles were computed
      in multiple protic and aprotic solvents. The continuum solvation models, namely,
      polarizable continuum model (PCM), polarizable conductor calculation model
      (CPCM), and universal solvation model (SMD), gave relatively similar MAE's of
      ~1.6-1.7 kcal/mol for G4 and ~1.9-2.0 kcal/mol with M06/6-31+G(d,p). Partitioning
      the tautomer pairs into their respective molecular types, that is, aliphatic
      ketones, beta-dicarbonyls, and heterocycles, and separating out the aqueous
      versus nonaqueous results finds G4/PCM utilizing the UA0 cavity to be the overall
      most accurate combination. Free energies of activation, DeltaG(?), for the base
      catalyzed keto-enol interconversion of 2-nitrocyclohexanone were also computed
      using six bases and five solvents. The M06/6-31+G(d,p) reproduced the DeltaG(?)
      with MAE's of 1.5 and 1.8 kcal/mol using CPCM and SMD, respectively, for all
      combinations of base and solvent. That specific enolization was previously
      proposed to proceed via a concerted mechanism in less polar solvents but shift to
      a stepwise mechanism in more polar solvents. However, the current calculations
      suggest that the stepwise mechanism operates in all solvents. 

PMID- 26202335
TI  - Arnebin-1 promotes angiogenesis by inducing eNOS, VEGF and HIF-1alpha expression
      through the PI3K-dependent pathway.
AB  - Arnebin-1, a naphthoquinone derivative, plays a crucial role in the wound healing
      properties of Zicao (a traditional wound healing herbal medicine). It has been
      noted that Arnebin-1, in conjunction with vascular endothelial growth factor
      (VEGF), exerts a synergistic pro-angiogenic effect on human umbilical vein
      endothelial cells (HUVECs) and accelerates the healing process of diabetic
      wounds. However, the mechanisms responsible for the pro-angiogenic effect of
      arnebin-1 on HUVECs and its healing effect on diabetic wounds have not yet been
      fully elucidated. In this study, in an aim to elucidate these mechanisms of
      action of arnebin-1, we investigated the effects of arnebin-1 on the VEGF
      receptor 2 (VEGFR2) and the phosphoinositide 3-kinase (PI3K)-dependent signaling
      pathways in HUVECs treated with VEGF by western blot analysis. The pro-angiogenic
      effects of arnebin-1 on HUVECs, including its effects on proliferation and
      migration, were evaluated by MTT assay, Transwell assay and tube formation assay
      in vitro. The expression levels of hypoxia-inducible factor (HIF)-1alpha,
      endothelial nitric oxide synthase (eNOS) and VEGF were determined by western blot
      analysis in the HUVECs and wound tissues obtained from non-diabetic and diabetic
      rats. CD31 expression in the rat wounds was evaluated by immunofluorescence
      staining. We found that the activation of the VEGFR2 signaling pathway induced by
      VEGF was enhanced by arnebin-1. Arnebin-1 promoted endothelial cell
      proliferation, migration and tube formation through the PI3K-dependent pathway.
      Moreover, Arnebin-1 significantly increased the eNOS, VEGF and HIF-1alpha
      expression levels in the HUVECs and accelerated the healing of diabetic wounds
      through the PI3K-dependent signaling pathway. CD31 expression was markedly
      enhanced in the wounds of diabetic rats treated with arnebin-1 compared to the
      wounds of untreated diabetic rats. Therefore, the findings of the present study
      indicate that arnebin-1 promotes the wound healing process in diabetic rats by
      eliciting a pro-angiogenic response.

PMID- 26202337
TI  - More research is needed for local allergic rhinitis.

PMID- 26202339
TI  - Elastic constants of random solid solutions by SQS and CPA approaches: the case
      of fcc Ti-Al.
AB  - Special quasi-random structure (SQS) and coherent potential approximation (CPA)
      are techniques widely employed in the first-principles calculations of random
      alloys. Here we scrutinize these approaches by focusing on the local lattice
      distortion (LLD) and the crystal symmetry effects. We compare the elastic
      parameters obtained from SQS and CPA calculations, taking the random face
      centered cubic (fcc) Ti(1-x)Al(x) (0 <= x <= 1) alloy as an example of systems
      with components showing different electronic structures and bonding
      characteristics. For the CPA and SQS calculations, we employ the Exact Muffin-Tin
      Orbitals (EMTO) method and the pseudopotential method as implemented in the
      Vienna Ab initio Simulation Package (VASP), respectively. We show that the
      predicted trends of the VASP-SQS and EMTO-CPA parameters against composition are
      in good agreement with each other. The energy associated with the LLD increases
      with x up to x = 0.625 ~ 0.750 and drops drastically thereafter. The influence of
      the LLD on the lattice constants and C12 elastic constant is negligible. C11 and
      C44 decrease after atomic relaxation for alloys with large LLD, however, the
      trends of C11 and C44 are not significantly affected. In general, the
      uncertainties in the elastic parameters associated with the symmetry lowering
      turn out to be superior to the differences between the two techniques including
      the effect of LLD.

PMID- 26202338
TI  - Long-term phosphodiesterase 5 inhibitor administration reduces inflammatory
      markers and heat-shock proteins in cavernous tissue of Zucker diabetic fatty rat
      (ZDF/fa/fa).
AB  - Oxidative stress and nitrosative stress present in type 2 diabetes mellitus
      (T2DM) and metabolic syndrome (MS) induce inflammatory response in diverse
      tissues including cavernous tissue (CT). Heat-shock proteins (HSPs) have an
      important role in modulating and repairing tissue injury, although their
      participation in CT in T2DM is unclear. Beyond the specific action of
      phosphodiesterase type 5 inhibitors (PDE5i) on erectile function, it has been
      proposed that chronic administration of these agents improves endothelial
      function and ameliorates fibrotic changes. The aim of this study was to determine
      in CT of Zucker Diabetic Fatty (ZDF) rat, an experimental model of T2DM and MS:
      (1) the degree of oxidative stress and nitrosative stress; (2) the magnitude of
      inflammatory markers such as tumor necrosis factor-alpha (TNFalpha) and
      interleukin 6 (IL6); (3) immunoexpression of HSP70 and HSP27; (4) how a long-term
      PDE5i administration may modify these variables. For 6 months, (1) untreated ZDF;
      (2) ZDF+Sildenafil (Sil) and (3) control Lean Zucker Rat (LZR) received no
      treatment, were studied. Penises were processed for functional 'in vitro'
      studies, oxidative and nitrosative stress evaluation and immunohistochemistry in
      CT using TNFalpha; IL6; nitrotyrosine, HSP70 and HSP27 antibodies. ZDF+Sil
      presented better relaxation in corporal strips versus untreated ZDF. Furthermore,
      ZDF+Sil presented less lipoperoxidation in CT versus untreated ZDF. The activity
      of antioxidant enzymes CuZn superoxide dismutase (CuZnSOD) and glutathione
      peroxidase (GPx) was also reduced in untreated ZDF in CT along with a decrease in
      glutathione versus untreated ZDF. Nitrotyrosine expression was increased in
      untreated-ZDF rats versus ZDF+Sil and LZR. TNFalpha and IL6 were decreased in CT
      in ZDF+Sil versus untreated ZDF. Additionally, the expression of HSP70 and HSP27
      was reduced in CT in ZDF+Sil versus untreated ZDF. In conclusion, this study
      provides substantial evidence supporting a protective role of a long-term therapy
      with Sil on CT in a recognized animal model of T2DM and MS. 

PMID- 26202340
TI  - Prognostic value of RV isovolumic acceleration and tissue strain in moderate
      HFrEF.
AB  - BACKGROUND: Right ventricular (RV) dysfunction in heart failure (HF) with reduced
      left ventricular ejection fraction (LVEF) is associated with a poorer prognosis.
      No studies to date have investigated the prognostic utility of RV isovolumic
      acceleration (IVA) measured at tissue Doppler imaging (TDI) in HF. RV strain
      instead has been already correlated to a poorer prognosis in these patients. We
      aimed to assess the predictive value of both parameters in this context.
      MATERIALS AND METHODS: Sixty patients enrolled, NYHA II-III. Everyone underwent
      echocardiographic examination including TDI and strain analysis. Adverse event
      was defined as cardiovascular death or rehospitalization. RESULTS: Follow-up was
      32 +/- 13 months. Sixteen patients (26.7%) had an adverse event. IVA and RV
      strain were significantly lower in these patients. At logistic regression, they
      were both related to adverse event and their receiver operating characteristic
      (ROC) curve predictive (area under ROC 0.916 and 0.952, respectively). Kaplan
      Meier survival curves were significantly worse for both parameters inferior to
      their respective means (P < 0.001 for both). Univariate and multivariate analyses
      confirmed their better utility than tricuspid annular plane systolic excursion
      (TAPSE), fractional area change (FAC) or S' at TDI. CONCLUSIONS: our study
      demonstrated a useful prognostic role of RV strain and IVA, which are parameters
      of subclinical RV impairment. Patients with low values may benefit from a more
      aggressive therapy and a closer follow-up.

PMID- 26202341
TI  - Longitudinal relationship of diabetes-related distress and depressive symptoms:
      analysing incidence and persistence.
AB  - AIM: To investigate the longitudinal bi-directionality of diabetes-related
      distress and depressive symptoms. METHODS: A total of 509 patients receiving
      intensified insulin therapy completed the Centre for Epidemiological Studies
      Depression scale questionnaire for the assessment of depressive symptoms as well
      as the Problem Areas in Diabetes questionnaire for the assessment of diabetes
      related distress at baseline and at 6-month follow-up. Separate logistic and
      linear regression analyses for incidence and persistence were performed with
      demographic (age, gender, BMI) and medical (diabetes type, HbA1c , diabetes
      duration, late complications) control variables. RESULTS: Diabetes-related
      distress at baseline increased the risk of the incidence of elevated depressive
      symptoms by 2.56-fold (odds ratio 2.56; 95% CI 1.15-5.72; P = 0.02) when
      controlling for demographic and medical variables. In addition, diabetes-related
      distress at baseline doubled the chance of the persistence of elevated depressive
      symptoms (odds ratio 2.04, 95% CI 1.04-3.99; P = 0.04) when controlling for
      demographic and medical variables. The chance of having persistent elevated
      diabetes-related distress was increased 5.94-fold (odds ratio 5.94, 95% CI 2.60
      13.59; P < 0.0001) when elevated depressive symptoms were present at baseline.
      None of the medical variables had an influence on incidence or persistence.
      CONCLUSIONS: Diabetes-related distress was identified as a risk factor for the
      incidence and persistence of depressive symptoms. Reducing diabetes-related
      distress could help to prevent the development of elevated depressive symptoms.
      Furthermore, depressive symptoms were identified as an amplifier for diabetes
      related distress. Diabetes-related distress and depressive symptoms were
      independent risk factors for each other and should be monitored in routine care
      to disentangle their influence.

PMID- 26202342
TI  - A route to possible civil engineering materials: the case of high-pressure phases
      of lime.
AB  - Lime system has a chemical composition CaO, which is known as thermodynamically
      stable. The purpose here is to explore further possible phases under pressure, by
      means of variable-composition ab initio evolutionary algorithm. The present
      investigation shows surprisingly new stable compounds of lime. At ambient
      pressure we predict, in addition to CaO, CaO2 as new thermodynamically stable
      compound. The latter goes through two phases transition from C2/c space group
      structure to Pna21 at 1.5 GPa, and Pna21 space group structure to I4/mcm at 23.4
      GPa. Under increasing pressure, further compounds such as CaO3 become the most
      stable and stabilize in P-421m space group structure above 65 GPa. For the
      necessary knowledge of the new predicted compounds, we have computed their
      mechanical and electronic properties in order to show and to explain the main
      reasons leading to the structural changes. 

PMID- 26202343
TI  - An Overview of Products and Bias in Research.
AB  - Cannabis is a genus of annual flowering plant. Cannabis is often divided into 3
      species-Cannabis sativa, Cannabis indica, and Cannabis ruderalis-but there is
      significant disagreement about this, and some consider them subspecies of the
      same parent species. Cannabis sativa can grow to 5-18 feet or more, and often has
      a few branches. Cannabis indica typically grows 2-4 feet tall and is compactly
      branched. Cannabis ruderalis contains very low levels of Delta-9
      tetrahyocannabinol so is rarely grown by itself. Cannabis ruderalis flowers as a
      result of age, not light conditions, which is called autoflowering. It is
      principally used in hybrids, to enable the hybrid to have the autoflowering
      property. There are > 700 strains of cannabis, often with colorful names. Some
      are strains of 1 of the 3 subspecies. Many are crossbred hybrids. The strains can
      be named in a variety of ways: smell or lineage are common ways of naming. There
      are only a few rules about how the strains are named, and most strains' names do
      not follow the rules. There are 4 basic preparations of marijuana: bhang, hasish,
      oil (or hash oil), and leaves and/or buds. In medical marijuana trials,
      subjective outcomes are frequently used but blind breaking can introduce
      significant bias. Blind breaking occurs when patients figure out if they are in
      the control or the treatment group. When this occurs, there is significant
      overestimation of treatment effect.

PMID- 26202344
TI  - Alleviation of high fat diet-induced obesity by oligofructose in gnotobiotic mice
      is independent of presence of Bifidobacterium longum.
AB  - SCOPE: Diet-induced obesity is associated with changes in the gut microbiota and
      low-grade inflammation. Oligofructose was reported to ameliorate high fat diet
      induced metabolic disorders in mice by restoring the number of intestinal
      bifidobacteria. However, this has not been experimentally demonstrated. METHODS
      AND RESULTS: We fed conventional mice, germfree mice, mice associated with a
      simplified human gut microbiota composed of eight bacterial species including
      Bifidobacterium longum (SIHUMI), and mice associated with SIHUMI without B.
      longum a low fat diet (LFD), a high fat diet (HFD), or a HFD containing 10%
      oligofructose (HFD + OFS) for five weeks. We assessed body composition, bacterial
      cell numbers and metabolites, markers of inflammation, and gut permeability.
      Conventional mice fed HFD or HFD + OFS did not differ in body weight gain and
      glucose tolerance. The gnotobiotic mouse groups fed LFD or HFD + OFS gained less
      body weight and body fat, and displayed an improved glucose tolerance compared
      with mice fed HFD. These differences were not affected by the presence of B.
      longum. Mice fed HFD showed no signs of inflammation or increased intestinal
      permeability. CONCLUSION: The ability of oligofructose to reduce obesity and to
      improve glucose tolerance in gnotobiotic mice fed HFD was independent of the
      presence of B. longum.

PMID- 26202345
TI  - Systematic review of the relationship between artificial sweetener consumption
      and cancer in humans: analysis of 599,741 participants.
AB  - BACKGROUND: The effect of artificial sweetener consumption on cancer risk has
      been debated in animal models for over four decades. To further investigate this
      relationship, this study aims to synthesise results from several of the most
      recent studies in humans. METHODS: An online literature search was performed in
      MEDLINE from 2003 to 2014 using Ovid, PubMed, Web of Science, and Scopus using
      keywords 'artificial', 'sweetener' and 'cancer'. Ninety-two results were then
      manually assessed for eligibility. Studies were included if the relationship
      between artificial sweeteners and cancer was their central hypothesis, and if
      they adjusted for age, gender, smoking status and body mass index. Extracted data
      included study design, patient characteristics, outcome measure and results.
      RESULTS: In the five publications that satisfied the inclusion criteria,
      significant direct associations with artificial consumption were found for
      laryngeal (odds ratio, OR 2.34, 95% CI: 1.20-4.55), urinary tract tumours (OR
      2.12, 95% CI: 1.22-3.89), non-Hodgkin lymphoma in men (RR 1.31, 95% CI: 1.01
      1.72), multiple myeloma in men (RR 2.02, 95% CI: 1.20-3.40) and leukaemia (RR
      1.42, 95% CI: 1.00-2.02). Inverse relationships were found in breast (OR 0.70,
      95% CI: 0.54-0.91, p trend = 0.015) and ovarian (OR 0.56, 95% CI: 0.38-0.81, p
      trend < 0.001) cancers. CONCLUSION: The statistical value of this review is
      limited by the heterogeneity and observational designs of the included studies.
      Although there is limited evidence to suggest that heavy consumption may increase
      the risk of certain cancers, overall the data presented are inconclusive as to
      any relationship between artificial sweeteners and cancer.

PMID- 26202346
TI  - Inhibitory Effect of Apigenin on Pharmacokinetics of Venlafaxine in vivo and in
      vitro.
AB  - OBJECTIVE: This study was conducted to investigate the effects of orally
      administered apigenin on the pharmacokinetics of venlafaxine (VEN) in rats and on
      the metabolism of VEN in human and rat liver microsomes in vitro. METHODS: Ten
      healthy male SD rats were randomly divided into 2 groups: A group (control
      group), B group (a single dose of 250 mg/kg apigenin). A single dose of 20 mg/kg
      VEN was administered orally 30 min after administration of apigenin (250 mg/kg).
      VEN plasma levels were measured by HPLC with fluorescence detection, and
      pharmacokinetic parameters were calculated by DAS 3.0 software. RESULTS: The
      single dose of 250 mg/kg apigenin significantly increased the AUC0-t of VEN by
      40.9% (p < 0.05) and obviously increased the peak plasma concentration (Cmax) of
      VEN (p < 0.05). Furthermore, apigenin showed inhibitory effect on human and rat
      microsomes and the IC50 of apigenin was 58.37 and 25.73 MUmol/l, respectively.
      CONCLUSIONS: Our results indicated that an intake of apigenin could increase VEN
      plasma levels and some of its pharmacokinetic parameters (AUC, Tmax). Thus, more
      attention should be paid when VEN was administrated combined with apigenin.

PMID- 26202348
TI  - Synthesis, structure, and photoluminescence properties of novel KBaSc2 (PO4 )3
      :Ce(3+) /Eu(2+) /Tb(3+) phosphors for white-light-emitting diodes.
AB  - A series of novel KBaSc2 (PO4 )3 :Ce(3+) /Eu(2+) /Tb(3+) phosphors are prepared
      using a solid-state reaction. X-ray diffraction analysis and Rietveld structure
      refinement are used to check the phase purity and crystal structure of the
      prepared samples. Ce(3+) - and Eu(2+) -doped phosphors both have broad excitation
      and emission bands, owing to the spin- and orbital-allowed electron transition
      between the 4f and 5d energy levels. By co-doping the KBaSc2 (PO4 )3 :Eu(2+) and
      KBaSc2 (PO4 )3 :Ce(3+) phosphors with Tb(3+) ions, tunable colors from blue to
      green can be obtained. The critical distance between the Eu(2+) and Tb(3+) ions
      is calculated by a concentration quenching method and the energy-transfer
      mechanism for Eu(2+) ->Tb(3+) is studied by utilizing the Inokuti-Hirayama model.
      In addition, the quantum efficiencies of the prepared samples are measured. The
      results indicate that KBaSc2 (PO4 )3 :Eu(2+) ,Tb(3+) and KBaSc2 (PO4 )3 :Ce(3+)
      ,Tb(3+) phosphors might have potential applications in UV-excited white-light
      emitting diodes. 

PMID- 26202347
TI  - Addiction to MTH1 protein results in intense expression in human breast cancer
      tissue as measured by liquid chromatography-isotope-dilution tandem mass
      spectrometry.
AB  - MTH1 protein sanitizes the nucleotide pool so that oxidized 2'-deoxynucleoside
      triphosphates (dNTPs) cannot be used in DNA replication. Cancer cells require
      MTH1 to avoid incorporation of oxidized dNTPs into DNA that results in mutations
      and cell death. Inhibition of MTH1 eradicates cancer, validating MTH1 as an
      anticancer target. By overexpressing MTH1, cancer cells may mediate cancer growth
      and resist therapy. To date, there is unreliable evidence suggesting that MTH1 is
      increased in cancer cells, and available methods to measure MTH1 levels are
      indirect and semi-quantitative. Accurate measurement of MTH1 in disease-free
      tissues and malignant tumors of patients may be essential for determining if the
      protein is truly upregulated in cancers, and for the development and use of MTH1
      inhibitors in cancer therapy. Here, we present a novel approach involving liquid
      chromatography-isotope-dilution tandem mass spectrometry to positively identify
      and accurately quantify MTH1 in human tissues. We produced full length (15)N
      labeled MTH1 and used it as an internal standard for the measurements. Following
      trypsin digestion, seven tryptic peptides of both MTH1 and (15)N-MTH1 were
      identified by their full scan and product ion spectra. These peptides provided a
      statistically significant protein score that would unequivocally identify MTH1.
      Next, we identified and quantified MTH1 in human disease-free breast tissues and
      malignant breast tumors, and in four human cultured cell lines, three of which
      were cancer cells. Extreme expression of MTH1 in malignant breast tumors was
      observed, suggesting that cancer cells are addicted to MTH1 for their survival.
      The approach described is expected to be applicable to the measurement of MTH1
      levels in malignant tumors vs. surrounding disease-free tissues in cancer
      patients. This attribute may help develop novel treatment strategies and MTH1
      inhibitors as potential drugs, and guide therapies. 

PMID- 26202349
TI  - Blood donor deferral for men who have sex with men: the Blood Donation Rules
      Opinion Study (Blood DROPS).
AB  - BACKGROUND: In the United States, any man who discloses having had sex with
      another man (MSM) even once since 1977 is currently deferred from donating blood.
      A study was conducted to assess noncompliance with the policy at four
      geographically dispersed blood centers. STUDY DESIGN AND METHODS: Male donors 18+
      years of age with e-mail addresses were randomly selected and invited to complete
      a confidential online survey between August and October 2013. No additional
      recruitment e-mails were sent. Survey content included demographics, sexual
      history, donation history, compliance with the policy, and opinions about current
      and modified policies. RESULTS: Response rate was 11.5% but varied by center
      (6.3% to 21.7%). Of 3183 completed surveys, 2.6% of respondents (95% confidence
      interval, 2.1%-3.2%) reported donation after male-male sex. Noncompliance was not
      statistically different among the centers (p = 0.1), but was related to age with
      5.7, 4.6, 2.5, and 1.0% of donors 18 to 24, 25 to 34, 35 to 54, and 50+ years of
      age, respectively, reporting noncompliance (p < 0.001). Of all respondents, 6.8%
      reported at least six female and 0.3% reported at least six male sex partners in
      the past 5 years. Opinions about the current MSM policy were mixed with
      noncomplying donors more supportive of change than complying donors. Approximatey
      half of noncompliers indicated they would adhere to a 1-year deferral.
      CONCLUSION: Noncompliance with the MSM policy is evident and may be increasing
      compared to earlier data. Any change from the current policy will require close
      monitoring to determine whether it affects residual risk of HIV in the US blood
      supply.

PMID- 26202350
TI  - Wnt/beta-Catenin and Wnt5a/Ca Pathways Regulate Proliferation and Apoptosis of
      Keratinocytes in Psoriasis Lesions.
AB  - BACKGROUND / AIMS: Wnt5a is overexpressed in psoriasis lesions, however the
      mechanism by which Wnt5a is involved in the pathogenesis of psoriasis is not
      clear. To address this, the expression of Wnt5a in psoriatic lesions and its
      effect on keratinocyte cell proliferation and apoptosis was examined in vitro.
      METHODS: The expression levels of WNT5A, and genes encoding its receptors
      frizzled2 (FZD2) and frizzled5 (FZD5) were examined in samples obtained from
      individuals with psoriasis and healthy controls. Knockdown of Wnt5a with short
      interfering (si)RNAs was performed in cultured HaCaT keratinocytes and normal
      human keratinocytes (NHK), and the expression of Wnt5a, protein kinase C (PKC),
      and beta-catenin were determined, and cell cycle activity, proliferation and
      apoptosis were assessed. RESULTS: The expression of WNT5A, FZD2 and FZD5 mRNA and
      protein were increased in psoriatic lesions. Wnt5a knockdown suppressed
      proliferation and induced apoptosis in HaCaT and NHK cells. Additionally,
      expression of PCNA, MKI67, CCND1, BCL2, CTNNB1, and genes encoding PKC and
      survivin were downregulated, whereas CASP3 was upregulated. The mRNA levels of
      the Wnt pathway inhibitors DKK1 and SFRP1 were upregulated, Western blotting
      analyses demonstrated reduction in beta-catenin and PKC protein levels.
      CONCLUSION: Knockdown of Wnt5a suppresses the proliferation of keratinocytes and
      induces apoptosis by inhibiting the Wnt/beta-catenin or Wnt5a/Ca(2+) pathways.

PMID- 26202351
TI  - PDK1 Activity Regulates Proliferation, Invasion and Growth of Hemangiomas.
AB  - BACKGROUND: Hemangiomas are common vascular endothelial cell tumors. Abnormally
      activated PI3K/Akt signaling pathway is one of the most important biological
      characteristics of Hemangioma. 3-phosphoinositide-dependent kinase 1(PDK1), an
      upstream protein of Akt, regulates the activity of Akt and its downstream
      kinases. The objective of this study is to explore the effect of PDK1 on
      malignant vascular tumors and their cell signaling mechanism in mice. METHODS:
      Mouse Hemangioendothelioma Endothelial Cells (EOMA cells) and Nu/Nu mice were
      used. The silencing of PDK1 was mediated by lentiviral shRNA. Western blotting,
      WST-1 proliferation assay, Matrigel invasion assay, and Xenograft vascular tumor
      model were utilized to examine the effects and mechanism of PDK1 growth,
      proliferation, and invasion of an Hemangioma. RESULTS: PDK1 deficiency
      significantly reduced the proliferation and invasion of EOMA cells in vitro, and
      depressed the growth of vascular tumor in vivo by decreasing the activity of Akt
      signaling pathway. CONCLUSION: We hypothesize that PDK1 plays a significant role
      in the progression and growth of vascular tumors and targeting PDK1 may thus be
      considered in their treatment.

PMID- 26202352
TI  - The Effect of cAMP-PKA Activation on TGF-beta1-Induced Profibrotic Signaling.
AB  - BACKGROUND: The cAMP-PKA signaling pathway and TGF-beta1-dependent fibrosis
      pathways are of particular importance in ADPKD progression, but the cross-talk
      between these pathways remains unclear. Therefore, we used an MDCK-cell model and
      embryonic kidney-cyst model to study the regulatory role of cAMP-PKA signaling in
      the TGF-beta1 induced fibrotic process. METHOD AND RESULTS: Pkd1(flox/flox); Ksp
      Cre and Pkd1(+/+); Ksp-Cre mice were used as an in vivo model. Increased kidney
      volume, renal cysts formation and up-regulation of the fibrosis-related proteins
      TGF-beta1, connective tissue growth factor (CTGF), and fibronectin (FN) can be
      observed in Pkd1(flox/flox); Ksp-Cre mice. In an embryonic kidneys-cyst model,
      TGF-beta1, FN and collagen type I were highly expressed. Western blotting
      revealed the obviously up-regulation of TGF-beta1, CTGF, FN and collagen type I
      expression following forskolin treatment in MDCK cells. Selective PKA inhibition
      with H89 may partially reversed the above effects. Pretreatment with the TGF-beta
      RI kinase inhibitor VI SB431542 suppressed the increased expression of CTGF, FN
      and collagen type I caused by forskolin. Our data also indicate that forskolin
      inhibited TGF-beta-induced ERK1/2 phosphorylation and FN up-regulation. ERK
      inhibition useing PD98059 significantly inhibited the expression of CTGF, FN and
      collagen type I caused by TGF-beta1. CONCLUSIONS: The cAMP-PKA signaling pathway
      can directly promote the production of TGF-beta1 and/or TGF-beta1-dependent
      fibrogenetic molecules in MDCK cells and embryonic kidney cysts, but when TGF
      beta1 and its downstream pathways were highly expressed in MDCK cells, cAMP-PKA
      had a significantly negative effect on TGF-beta1 induced p-ERK1/2 and FN
      expression.

PMID- 26202353
TI  - Alpha1-Adrenergic Receptor Activation Stimulates Calcium Entry and Proliferation
      via TRPC6 Channels in Cultured Human Mesangial Cells.
AB  - BACKGROUND AND AIMS: There is accumulating evidence that sympathetic nervous
      hyperactivity contributes to the pathogenesis of glomerular sclerosis independent
      of blood pressure effects. A previous study showed that alpha1-adrenoceptor
      (alpha1-AR) antagonists inhibit mesangial cell (MC) proliferation. However, the
      underlying mechanism remains unclear. METHODS AND RESULTS: We found that alpha1
      AR is expressed in a human mesangial cell line. The alpha1-AR agonist
      phenylephrine (PE) induced Ca(2+) influx as well as release from intracellular
      Ca(2+) stores. Blockade of TRPC6 with siRNA, anti-TRPC6 antibodies and a TRPC
      blocker attenuated the PE-induced [Ca(2+)]i increase. Additionally, the PE
      induced [Ca(2+)]i increase was phospholipase C dependent. Furthermore, PE induced
      a [Ca(2+)]i increase even when the intracellular Ca(2+) stores were already
      depleted. This effect was mimicked by an analog of diacylglycerol. These results
      suggested that, upon alpha1-AR stimulation, TRPC6 mediates Ca(2+) influx via a
      receptor-operated Ca(2+) entry mechanism. Finally, TRPC6 contributes to the PE
      induced MC proliferation. The mechanisms are associated with the extracellular
      signal-regulated kinase (ERK) signaling pathway because blockade of TRPC6 and
      chelation of extracellular Ca(2+) abrogated PE-induced ERK1/2 abrogated PE
      induced ERK1/2 phosphorylation. CONCLUSION: TRPC6 channels are involved in alpha1
      AR activation-induced Ca(2+) entry, which mediates proliferation via ERK
      signaling in human MCs.

PMID- 26202354
TI  - Enhanced Glucose Tolerance and Pancreatic Beta Cell Function by Low Dose Aspirin
      in Hyperglycemic Insulin-Resistant Type 2 Diabetic Goto-Kakizaki (GK) Rats.
AB  - BACKGROUND/AIM: Type 2 diabetes is the most common metabolic disorder,
      characterized by insulin resistance and pancreatic islet beta-cell failure. The
      most common complications associated with type 2 diabetes are hyperinsulinemia,
      hyperglycemia, hyperlipidemia, increased inflammatory and reduced insulin
      response. Aspirin (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs)
      have been associated with the prevention of diabetes, obesity and related
      cardiovascular disorders. Aspirin has been used in many clinical and experimental
      trials for the prevention of diabetes and associated complications. METHODS: In
      this study, five month old Goto-Kakizaki (GK) rats, which showed signs of mild
      hyperglycemia (fasting blood glucose 80-95 mg/dl vs 55-60 mg/dl Wistar control
      rats) were used. Two subgroups of GK and Wistar control rats were injected
      intraperitoneally with 100 mg aspirin/kg body weight/ day for 5 weeks. Animals
      were sacrificed and blood and tissues were collected after performing glucose
      tolerance (2 h post 2g IP glucose ingestion) tests in experimental and control
      groups. RESULTS: Aspirin caused a moderate decrease in hyperglycemia. However, we
      observed a significant improvement in glucose tolerance after ASA treatment in GK
      rats compared to the nondiabetic Wistar rats. Also, the ASA treated GK rats
      exhibited a significant decrease in insulinemia. ASA treatment also caused a
      marked reduction in the pro-inflammatory prostaglandin, PGE2, which was
      significantly higher in GK rats. On the other hand, no significant organ toxicity
      was observed after ASA treatment at this dose and time period. However, the total
      cholesterol and lipoprotein levels were significantly increased in GK rats, which
      decreased after ASA treatment. Immunofluorescence staining for insulin/glucagon
      secreting pancreatic cells showed improved beta-cell structural and functional
      integrity in ASA-treated rats which was also confirmed by SDS-PAGE and Western
      blot analysis. CONCLUSION: The improved glucose tolerance in ASA-treated GK rats
      may be associated with increased insulin responses due to the anti-inflammatory
      properties of ASA and enhanced nitric oxide (NO) level which facilitated insulin
      signaling and energy utilization in target tissues. These results may have
      implications in determining the therapeutic use of ASA in insulin-resistant type
      2 diabetes.

PMID- 26202355
TI  - rs2910164 Polymorphism Confers a Decreased Risk for Pulmonary Hypertension by
      Compromising the Processing of microRNA-146a.
AB  - OBJECTIVE: To identify the association between rs2910164 polymorphism and
      development of pulmonary hypertension, as well as underlying molecular mechanism.
      METHODS AND RESULTS: 281 patients diagnosed with pulmonary hypertension and 325
      normal controls were recruited, and rs2910164 genotype was determined in each
      participant: As a result, the rs2910164 polymorphism was significantly associated
      with the development of pulmonary hypertension after adjusting some potential
      confounding factors. Additionally, lung tissue samples were obtained from 39
      patients who received surgical intervention for lung cancer, and mRNA and protein
      expression levels of miR-146a, COX-2 and PGI2 production were examined.
      Furthermore, we confirmed COX-2 is a target of miR-146a in pulmonary smooth
      muscle cells, and identified a differentially expressed miR-146a and COX-2 in
      each rs2910164 genotype group. We observed a significant association between
      rs2910164 polymorphism and the levels of either COX-2 or PGI2 using real-time PCR
      and western blot. In conclusion, the results of this study demonstrate that the
      rs2910164 CC and GC genotype is associated with a decreased risk of pulmonary
      hypertension, which could be attributed to defective miRNA processing and
      compromised ability to inhibit production of COX-2 and PGI2.

PMID- 26202356
TI  - Factors Affecting the Recurrence of Giant Cell Tumor of Bone After Surgery: A
      Clinicopathological Study of 80 Cases from a Single Center.
AB  - BACKGROUND/AIMS: This aim of the present study was to identify specific markers
      determining the recurrence of the giant cell tumor of bone (GCTB). METHODS: This
      study involved the clinicopathological analysis of 80 cases. All of the clinical
      features, pathological fracture, Campanacci grade, histological features and
      surgical methods were reviewed. Immunohistochemistry was used to detect the
      expression of Ki-67, CD147, mutant p53 and p63 in GCTB. Comparisons between
      different groups were performed using the Chi-square test. The risk factors
      affecting recurrence were analyzed using a binary logistic model. Kaplan-Meier
      analysis was employed for the survival analysis between the groups. Cell
      proliferation assays, migration and invasion assays were used to detect the
      function of CD147 on GCTB in vitro. RESULTS: The univariate analysis showed that
      Ki-67 and CD147 expression, pathological fracture, Campanacci grade and surgical
      method were associated with recurrence. The multivariate analysis revealed that
      CD147 expression, Campanacci grade and surgical method were the factors affecting
      GCTB recurrence. In addition, the Kaplan-Meier analysis revealed that these
      factors affected tumor-free survival time. In vitro study revealed that the CD147
      knockdown by small interfering RNA (siRNA) technique dramatically reduced the
      proliferation, migration and invasion of GCTB. CONCLUSION: Our results suggest
      that CD147 may serve as an adequate marker for GCTB recurrence. Campanacci grade
      is a risk factor for GCTB recurrence, which is also affected by the surgical
      method used.

PMID- 26202357
TI  - Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia
      Reperfusion Injury.
AB  - BACKGROUND/AIMS: Ischemia/reperfusion (I/R) injury is the main cause of both
      primary graft dysfunction and primary non-function of liver allografts.
      Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R
      oxidative injury. Delta-9-tetrahydrocannabinol (THC), a cannabinoid agonist, is
      the active components of marijuana. In this study we examined the role of
      ultralow dose THC (0.002mg/kg) in the protection of livers from I/R injury. This
      extremely low dose of THC was previously found by us to protect the mice brain
      and heart from a variety of insults. METHODS: C57Bl Mice were studied in in vivo
      model of hepatic segmental (70%) ischemia for 60min followed by reperfusion for 6
      hours. RESULTS: THC administration 2h prior to the induction of hepatic I/R was
      associated with significant attenuated elevations of: serum liver transaminases
      ALT and AST, the hepatic oxidative stress (activation of the intracellular
      signaling CREB pathway), the acute proinflammatory response (TNF-alpha, IL
      1alpha, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway
      activation). This was followed by cell death (the cleavage of the pro-apoptotic
      caspase 3, DNA fragmentation and TUNEL) after 6 hours of reperfusion.
      Significantly less hepatic injury was detected in the THC treated I/R mice and
      fewer apoptotic hepatocytes cells were identified by morphological criteria
      compared with untreated mice. CONCLUSION: A single ultralow dose THC can reduce
      the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury.
      THC may serve as a potential target for therapeutic intervention in hepatic I/R
      injury during liver transplantation, liver resection and trauma.

PMID- 26202358
TI  - Inhibition of Recombining Binding Protein Suppressor of Hairless (RBPJ) Impairs
      the Growth of Prostate Cancer.
AB  - BACKGROUND/AIMS: Notch signaling pathway regulates cancer cell growth. RBPJ is a
      key transcription factor downstream of Notch receptor activation, whereas the
      role of RBPJ in carcinogenesis of prostate cancer is ill-defined. METHODS: Here,
      we evaluated the effects of RBPJ inhibition on the growth of prostate cancer
      cells. We knocked down RBPJ in prostate cancer cells by a short hairpin
      interfering RNA (shRNA). We measured cell growth by an MTT assay. We analyzed the
      levels of cell-cycle-associated proteins by Western blot. RESULTS: We found that
      shRNA for RBPJ efficiently inhibited RBPJ expression in prostate cancer cells,
      resulting in a significant decrease in the cell growth. Further, RBPJ-mediated
      cell-growth inhibition appeared to be resulting from alteration of cell-cycle
      inhibitors p21 and p27, cell-cycle activators CDK2, CDK4 and CyclinD1, and
      apoptosis-suppressor Bcl-2. CONCLUSION: Our data suggest that shRNA intervention
      of RBPJ expression could be a promising therapeutic approach for treating human
      prostate cancer.

PMID- 26202359
TI  - Inhibition of Notch Signaling Promotes the Adipogenic Differentiation of
      Mesenchymal Stem Cells Through Autophagy Activation and PTEN-PI3K/AKT/mTOR
      Pathway.
AB  - BACKGROUND: The Notch signaling pathway is implicated in a broad range of
      developmental processes, including cell fate decisions. This study was designed
      to determine the role of Notch signaling in adipogenic differentiation of human
      bone marrow derived MSCs (BM-MSCs). METHODS: The Notch signaling was inhibited by
      the gamma-secretase inhibitor N-[N-(3,5-difluor- ophenacetyl-L-alanyl)]-S
      phenylglycine t-butylester (DAPT). The markers involving adipogenic
      differentiation of MSCs, the relative pathway PTEN-PI3K/Akt/mTOR and autophagy
      activation were then analyzed. Furthermore, the autophagy inhibitor chloroquine
      (CQ) and 3-methyladenine (3-MA) were used to study the role of autophagy in the
      DAPT-induced the adipogenic differentiation of MSCs. RESULTS: We first confirmed
      the down -regulation of Notch gene expression during MSCs adipocyte
      differentiation, and showed that the inhibition of Notch signaling significantly
      enhanced adipogenic differentiation of MSCs. Furthermore, Notch inhibitor DAPT
      induced early autophagy by acting on PTEN-PI3K/Akt/mTOR pathway. The autophagy
      inhibitor CQ and 3-MA dramatically abolished the effects of DAPT-induced
      autophagy and adipogenic differentiation of MSCs. CONCLUSION: Our results
      indicate that inhibition of Notch signaling could promote MSCs adipogenesis
      mediated by autophagy involving PTEN-PI3K/Akt/mTOR pathway. Notch signaling could
      be a novel target for regulating the adipogenic differentiation of MSCs.

PMID- 26202360
TI  - Cordyceps Militaris Alleviates Severity of Murine Acute Lung Injury Through
      miRNAs-Mediated CXCR2 Inhibition.
AB  - BACKGROUND/AIMS: Acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS) are lethal diseases in humans, and the current treatments have limited
      therapeutic effects. Cordyceps militaris (CM) is a caterpillar-grown traditional
      medicinal mushroom, and has been used as a natural invigorant for longevity,
      endurance, and vitality in China. Recently, purified extracts from CM have been
      shown to have beneficial effects on various diseases including cancer.
      Nevertheless, a role of CM in ALI has not been examined previously. METHODS:
      Here, we used a bleomycin-induced ALI model to study the effects of CM on the
      severity of ALI in mice. The levels of CXCR2, a receptor for Interleukin 8 (IL-8)
      in pulmonary microvascular endothelial cells, were examined in different
      experimental groups. The levels of microRNA (miR)-1321 and miR-3188 were also
      examined in lung samples and in CM. Adeno-associated viruses carrying miR-1321
      and miR-3188 were injected into bleomycin-treated mice for evaluation their
      effects on the severity of ALI. RESULTS: CM treatment significantly alleviated
      the severity of bleomycin-induced ALI in mice. The increases in lung CXCR2 by
      bleomycin were significantly reduced by CM at protein level, but not at mRNA
      level. CM contained high levels of 2 miRNAs (miR-1321 and miR-3188) that target
      3'-UTR of CXCR2 mRNA to inhibit its expression. Overexpression of miR-1321 and
      miR-3188 in mouse lung through AAV-mediated gene therapy mimicked the effects of
      CM. CONCLUSION: CM may alleviate severity of murine ALI through miRNAs-mediated
      CXCR2 inhibition.

PMID- 26202361
TI  - Inflammasome Inhibition Suppresses Alveolar Cell Permeability Through Retention
      of Neuregulin-1 (NRG-1).
AB  - BACKGROUND: Neuregulin (NRG)-1-human epidermal receptor (HER)-2 signaling pathway
      is a key regulator of IL-1beta-mediated pulmonary inflammation and epithelial
      permeability. The inflammasome is a newly discovered molecular platform required
      for caspase-1 activation and maturation of IL-1beta. However, the role of the
      inflammasome in NRG-1-HER2 signaling-mediated alveolar cell permeability is
      unknown. METHODS: The inflammasome was activated or inhibited in THP-1 cells;
      supernatants from these cells were added to A549 cells and human small airway
      epithelial cells (HSAEC). The protein expression of NRG-1 and phospho-HER2
      (pHER2) were measured by Western blot analysis and epithelial permeability was
      measured using Lucifer yellow dye. RESULTS: Results reveal that alveolar
      permeability in A549 cells and HSAEC is increased when treated with supernatants
      of inflammasome-activated THP-1 cells. Alveolar permeability is significantly
      suppressed when treated with supernatant of inflammasome-inhibited THP-1 cells.
      Inflammasome-mediated permeability is decreased when A549 cells and HSAEC are
      pretreated with IL-1beta receptor antagonist (IL-1betaRA). In addition, HER2
      kinase inhibitor AG825 or NRG-1 inhibitor TAPI inhibits inflammasome-mediated
      permeability in A549 cells and HSAEC demonstrating critical roles of IL-1beta,
      NRG-1, and HER2 in inflammasome-mediated alveolar permeability. CONCLUSION: These
      findings suggest that inflammasome-induced alveolar cell permeability is mediated
      by NRG-1/HER2 signaling through IL-1beta regulation.

PMID- 26202362
TI  - Acetylcholine Inhibits LPS-Induced MMP-9 Production and Cell Migration via the
      alpha7 nAChR-JAK2/STAT3 Pathway in RAW264.7 Cells.
AB  - BACKGROUND: Excessive activation of matrix metalloproteinase 9 (MMP-9) has been
      found in several inflammatory diseases. Previous studies have shown that
      acetylcholine (ACh) reduced the levels of pro-inflammatory cytokines and
      decreased tissue damage. Therefore, this study was designed to explore the
      potential effects and mechanisms of ACh on MMP-9 production and cell migration in
      response to lipopolysaccharide (LPS) stimulation in RAW264.7 cells. METHODS: MMP
      9 expression and activity were induced by LPS in RAW264.7 cells, and examined by
      real-time PCR, western blotting and gelatin zymography, respectively. ELISA was
      used to determine the changes in MMP-9 secretion among the groups. Macrophage
      migration was evaluated using transwell migration assay. Knockdown of alpha7
      nicotinic acetylcholine receptor (alpha7 nAChR) expression was performed using
      siRNA transfection. RESULTS: Pre-treatment with ACh inhibited LPS-induced MMP-9
      production and macrophage migration in RAW264.7 cells. These effects were
      abolished by the alpha7 nAChR antagonist methyllycaconitine (MLA) and alpha7
      nAChR siRNA. The alpha7 nAChR agonist PNU282987 was found to have an effect
      similar to that of ACh. Moreover, ACh enhanced the expression of JAK2 and STAT3,
      and the JAK2 inhibitor AG490 and the STAT3 inhibitor static restored the effect
      of ACh. Meanwhile, ACh decreased the phosphorylation and nuclear translocation of
      NF-kappaB, and this effect was abrogated in the presence of MLA. In addition, the
      JAK2 and STAT3 inhibitor abolished the inhibitory effects of ACh on
      phosphorylation of NF-kappaB. CONCLUSIONS: Activation of alpha7 nAChR by ACh
      inhibited LPS-induced MMP-9 production and macrophage migration through the
      JAK2/STAT3 signaling pathway. These results provide novel insights into the anti
      inflammatory effects and mechanisms of ACh.

PMID- 26202363
TI  - Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial
      Parasympathetic Remodeling through MAPKs/Neurturin Pathway.
AB  - BACKGROUND/AIMS: Angiotensin II receptor blockers (ARBs) have been proved to be
      effective in preventing atrial structural and electrical remodelinq in atrial
      fibrillation (AF). Previous studies have shown that parasympathetic remodeling
      plays an important role in AF. However, the effects of ARBs on atrial
      parasympathetic remodeling in AF and the underlying mechanisms are still unknown.
      METHODS: Canines were divided into sham-operated, pacing and valsartan + pacing
      groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II
      (Ang II) and Ang II + valsartan groups, respectively. Atrial parasympathetic
      remodeling was quantified by immunocytochemical staining with anti-choline
      acetyltransferase (ChAT) antibody. Western blot was used to analysis the protein
      expression of neurturin. RESULTS: Both inducibility and duration were increased
      in chronic atrial rapid-pacing canine model, which was significantly inhibited by
      the treatment with valsartan. The density of ChAT-positive nerves and the protein
      level of neurturin in the atria of pacing canines were both increased than those
      in sham-operated canines. Ang II treatment not only induced atrial
      parasympathetic remodeling in rats, but also up-regulated the protein expression
      of neurturin. Valsartan significantly prevented atrial parasympathetic
      remodeling, and suppressed the protein expression of neurturin. Meanwhile,
      valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in
      cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin
      up-regulation induced by Ang II. CONCLUSION: Parasympathetic remodeling was
      present in animals subjected to rapid pacing or Ang II infusion, which was
      mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial
      parasympathetic remodeling and the occurrence of AF via inhibiting
      MAPKs/neurturin pathway.

PMID- 26202364
TI  - The Down-Regulation of MicroRNA-497 Contributes to Cell Growth and Cisplatin
      Resistance Through PI3K/Akt Pathway in Osteosarcoma.
AB  - BACKGROUND: Down-expression of microRNA-497 (miR-497) was often found in
      malignancies. The purposes of this study were to determine the expression of miR
      497 in human osteosarcoma and to establish the association between miR-497
      expression with cell survival and the sensitivity to cisplatin in human
      osteosarcoma cells. METHODS: The effects of ectopic miR-497 expression on the
      cell survival and cisplatin sensitivity in osteosarcoma cells were measured by
      the Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time PCR (qRT-PCR) was
      utilized to determine the expression of miR-497. The effects of ectopic miR-497
      expression on the expression of VEGFA, Akt and p-Akt were determined by western
      blot. RESULTS: Real-time quantitative PCR analysis revealed that miR-497 was
      significantly down-regulated in osteosarcoma tissues and in the osteosarcoma cell
      line SAOS-2 compared with adjacent nontumorous osteosarcoma tissues and normal
      human osteoblasts. Up-regulation of miR-497 inhibited cell survival and enhanced
      the sensitivity to cisplatin in osteosarcoma cells. In addition, knockdown of miR
      497 induced osteosarcoma cells growth and cisplatin resistance. Luciferase
      reporter assay and western blot confirmed that VEGFA was a direct target of miR
      497. PI3K inhibitor LY294002 abrogated miR-497 inhibitors induced cisplatin
      resistance. CONCLUSION: Taken together, our results suggest that miR-497
      modulates the sensitivity to cisplatin at least in part through PI3K/Akt pathway
      in osteosarcoma cells.

PMID- 26202365
TI  - Thrombopoietin Protects Cardiomyocytes from Iron-Overload Induced Oxidative
      Stress and Mitochondrial Injury.
AB  - BACKGROUND/AIMS: Thalassaemia accompanied with iron-overload is common in Hong
      Kong. Iron-overload induced cardiomyopathy is the commonest cause of morbidity
      and mortality in patients with beta-thalassaemia. Chronic iron-overload due to
      blood transfusion can cause cardiac failure. Decreased antioxidant defence and
      increased ROS production may lead to oxidative stress and cell injury. Iron
      overload may lead to heart tissue damage through lipid peroxidation in response
      to oxidative stress, and a great diversity of toxic aldehydes are formed when
      lipid hydroperoxides break down in heart and plasma. METHODS: Iron entry into
      embryonic heart H9C2 cells was determined by calcein assay using a fluorometer.
      Reactive oxygen species (ROS) production in cells treated with FeCl3 or
      thrombopoietin (TPO) was monitored by using the fluorescent probe H2DCFDA.
      Changes in mitochondrial membrane potential of H9C2 cells were quantified by
      using flow cytometry. RESULTS: We demonstrated that iron induced oxidative stress
      and apoptosis in cardiomyocytes, and that iron increased ROS production and
      reduced cell viability in a dose-dependent manner. Iron treatment increased the
      proportion of cells with JC-1 monomers, indicating a trend of drop in the
      mitochondrial membrane potential. TPO exerted a cardio-protective effect on iron
      induced apoptosis. CONCLUSIONS: These findings suggest that iron-overload leads
      to the generation of ROS and further induces apoptosis in cardiomyocytes via
      mitochondrial pathways. TPO might exert a protective effect on iron-overload
      induced apoptosis via inhibiting oxidative stress and suppressing the
      mitochondrial pathways in cardiomyocytes.

PMID- 26202366
TI  - TRAP1 Provides Protection Against Myocardial Ischemia-Reperfusion Injury by
      Ameliorating Mitochondrial Dysfunction.
AB  - BACKGROUND: Tumor necrosis factor receptor-associated protein 1 (TRAP1), an
      essential mitochondrial chaperone is induced in rat hearts following
      ischemia/reperfusion (I/R), but its role in myocardial I/R injury is unclear. The
      present study examined the function of TRAP1 in cardiomyocyte
      hypoxia/reoxygenation injury in vitro and myocardial I/R injury in vivo. METHODS:
      HL-1 cardiomyocytes transfected with TRAP1 or vector were subjected to simulated
      I/R (SI/R) in vitro. Cell death and mitochondrial function were assessed. Wild
      type (WT) and TRAP1 knockout (TRAP1 KO) mice were subjected to cardiac I/R in
      vivo. The infarct size and myocardial apoptosis were determined. WT and TRAP1 KO
      cardiomyocytes were subjected to SI/R in vitro. Mitochondrial function was
      assessed. RESULTS: TRAP1 overexpression protects HL-1 cardiomyocytes from SI/R
      induced cell death in vitro. The reduced cell death was associated with decreased
      ROS generation, better-preserved mitochondrial ETC complex activity, membrane
      potential, and ATP production, as well as delayed mPTP opening. Loss of TRAP1
      aggravates SI/R-induced mitochondrial damage in cardiomyocytes in vitro and
      myocardial I/R injury and apoptosis in vivo. CONCLUSION: The results of the
      present study show that TRAP1 provides cardioprotection against myocardial I/R by
      ameliorating mitochondrial dysfunction.

PMID- 26202367
TI  - Protein & Peptide Letters. Editorial (Special Board Members Issue).

PMID- 26202368
TI  - Para-Tyrosine Supplementation Improves Insulin- and Liraglutide- Induced
      Vasorelaxation in Cholesterol-Fed Rats.
AB  - Former data of our workgroup indicated that the accumulation of oxidized amino
      acids (meta- and ortho-tyrosine) due to oxidative stress may play an important
      role in the impaired insulininduced vasoactive properties of different arterial
      segments. There are evidences, that incorporation of these amino acids into
      cellular proteins leads to certain hormonal resistances, which might be restored
      by supplementation with the physiologic isoform, para-tyrosine. Rats in the
      control group were kept on a regular diet, rats in the cholesterol-fed group
      received high-fat diet, while the third group of rats received high-fat diet with
      para-tyrosine supplementation for 16 weeks. Plasma cholesterol level was
      significantly higher in the cholesterol-fed group, while the level of cholesterol
      in the cholesterol+para-tyrosine group did not differ significantly from that of
      the controls. Plasma level of insulin after glucose stimulation was decreased in
      the cholesterol-fed group, while that in the para-tyrosine supplemented group did
      not differ significantly from the controls. Vascular para-, meta- and ortho
      tyrosine content was measured with HPLC. Elevated vascular meta-tyrosine/para
      tyrosine ratio of cholesterol fed rats could be avoided by para-tyrosine
      supplementation. Vascular response of the thoracic aorta to insulin and
      liraglutide was assessed by a DMT multi-myograph. Cholesterol feeding resulted in
      vascular insulin-and liraglutide resistance, which was restored by para-tyrosine
      supplementation. Incorporation of the oxidative stress induced pathological
      tyrosine isoforms leads to vascular-hormone-resistances. We show that the
      physiological amino acid para-tyrosine is capable of restoring
      hypercholesterolemia-induced increased meta-tyrosine content of the vascular
      wall, thus attenuating functional vascular damage. 

PMID- 26202369
TI  - Unlocking nature's treasure-chest: screening for oleaginous algae.
AB  - Micro-algae synthesize high levels of lipids, carbohydrates and proteins
      photoautotrophically, thus attracting considerable interest for the
      biotechnological production of fuels, environmental remediation, functional foods
      and nutraceuticals. Currently, only a few micro-algae species are grown
      commercially at large-scale, primarily for "health-foods" and pigments. For a
      range of potential products (fuel to pharma), high lipid productivity strains are
      required to mitigate the economic costs of mass culture. Here we present a screen
      concentrating on marine micro-algal strains, which if suitable for scale-up would
      minimise competition with agriculture for water. Mass-Spectrophotometric analysis
      (MS) of nitrogen (N) and carbon (C) was subsequently validated by measurement of
      total fatty acids (TFA) by Gas-Chromatography (GC). This identified a rapid and
      accurate screening strategy based on elemental analysis. The screen identified
      Nannochloropsis oceanica CCAP 849/10 and a marine isolate of Chlorella vulgaris
      CCAP 211/21A as the best lipid producers. Analysis of C, N, protein, carbohydrate
      and Fatty Acid (FA) composition identified a suite of strains for further
      biotechnological applications e.g. Dunaliella polymorpha CCAP 19/14,
      significantly the most productive for carbohydrates, and Cyclotella cryptica CCAP
      1070/2, with utility for EPA production and N-assimilation. 

PMID- 26202370
TI  - Spider foraging strategy affects trophic cascades under natural and drought
      conditions.
AB  - Spiders can cause trophic cascades affecting litter decomposition rates. However,
      it remains unclear how spiders with different foraging strategies influence
      faunal communities, or present cascading effects on decomposition. Furthermore,
      increased dry periods predicted in future climates will likely have important
      consequences for trophic interactions in detritus-based food webs. We
      investigated independent and interactive effects of spider predation and drought
      on litter decomposition in a tropical forest floor. We manipulated densities of
      dominant spiders with actively hunting or sit-and-wait foraging strategies in
      microcosms which mimicked the tropical-forest floor. We found a positive trophic
      cascade on litter decomposition was triggered by actively hunting spiders under
      ambient rainfall, but sit-and-wait spiders did not cause this. The drought
      treatment reversed the effect of actively hunting spiders on litter
      decomposition. Under drought conditions, we observed negative trophic cascade
      effects on litter decomposition in all three spider treatments. Thus, reduced
      rainfall can alter predator-induced indirect effects on lower trophic levels and
      ecosystem processes, and is an example of how such changes may alter trophic
      cascades in detritus-based webs of tropical forests. 

PMID- 26202371
TI  - Polymorphism in dopamine receptor D4 gene is associated with pigeon racing
      performance.

PMID- 26202372
TI  - Low-dose irradiation affects the functional behavior of oral microbiota in the
      context of mucositis.
AB  - The role of host-microbe interactions in the pathobiology of oral mucositis is
      still unclear; therefore, this study aimed to unravel the effect of irradiation
      on behavioral characteristics of oral microbial species in the context of
      mucositis. Using various experimental in vitro setups, the effects of irradiation
      on growth and biofilm formation of two Candida spp., Streptococcus salivarius and
      Klebsiella oxytoca in different culture conditions were evaluated. Irradiation
      did not affect growth of planktonic cells, but reduced the number of K. oxytoca
      cells in newly formed biofilms cultured in static conditions. Biofilm formation
      of K. oxytoca and Candida glabrata was affected by irradiation and depended on
      the culturing conditions. In the presence of mucins, these effects were lost,
      indicating the protective nature of mucins. Furthermore, the Galleria melonella
      model was used to study effects on microbial virulence. Irradiated K. oxytoca
      microbes were more virulent in G. melonella larvae compared to the nonirradiated
      ones. Our data indicate that low-dose irradiation can have an impact on
      functional characteristics of microbial species. Screening for pathogens like K.
      oxytoca in the context of mucosits could be useful to allow early detection and
      immediate intervention. 

PMID- 26202373
TI  - A human liver microphysiology platform for investigating physiology, drug safety,
      and disease models.
AB  - This paper describes the development and characterization of a microphysiology
      platform for drug safety and efficacy in liver models of disease that includes a
      human, 3D, microfluidic, four-cell, sequentially layered, self-assembly liver
      model (SQL-SAL); fluorescent protein biosensors for mechanistic readouts; as well
      as a microphysiology system database (MPS-Db) to manage, analyze, and model data.
      The goal of our approach is to create the simplest design in terms of cells,
      matrix materials, and microfluidic device parameters that will support a
      physiologically relevant liver model that is robust and reproducible for at least
      28 days for stand-alone liver studies and microfluidic integration with other
      organs-on-chips. The current SQL-SAL uses primary human hepatocytes along with
      human endothelial (EA.hy926), immune (U937) and stellate (LX-2) cells in
      physiological ratios and is viable for at least 28 days under continuous flow.
      Approximately, 20% of primary hepatocytes and/or stellate cells contain
      fluorescent protein biosensors (called sentinel cells) to measure apoptosis,
      reactive oxygen species (ROS) and/or cell location by high content analysis
      (HCA). In addition, drugs, drug metabolites, albumin, urea and lactate
      dehydrogenase (LDH) are monitored in the efflux media. Exposure to 180 MUM
      troglitazone or 210 MUM nimesulide produced acute toxicity within 2-4 days,
      whereas 28 MUM troglitazone produced a gradual and much delayed toxic response
      over 21 days, concordant with known mechanisms of toxicity, while 600 uM caffeine
      had no effect. Immune-mediated toxicity was demonstrated with trovafloxacin with
      lipopolysaccharide (LPS), but not levofloxacin with LPS. The SQL-SAL exhibited
      early fibrotic activation in response to 30 nM methotrexate, indicated by
      increased stellate cell migration, expression of alpha-smooth muscle actin and
      collagen, type 1, alpha 2. Data collected from the in vitro model can be
      integrated into a database with access to related chemical, bioactivity,
      preclinical and clinical information uploaded from external databases for
      constructing predictive models. 

PMID- 26202374
TI  - Light therapy modulates serotonin levels and blood flow in women with headache. A
      preliminary study.
AB  - In this study, we looked at the possible effects of low-level laser therapy
      (LLLT) on blood flow velocity, and serotonin (5-HT) and cholinesterase levels in
      patients with chronic headache associated with temporomandibular disorders (TMD).
      LLLT has been clinically applied over the past years with positive results in
      analgesia and without the report of any side effects. The understanding of
      biological mechanisms of action may improve clinical results and facilitate its
      indication. Ten patients presenting headache associated with TMD completed the
      study. An 830-nm infrared diode laser with power of 100 mW, exposure time of 34
      s, and energy of 3.4 J was applied on the tender points of masseter and temporal
      muscle. Blood flow velocity was determined via ultrasound Doppler velocimetry
      before and after laser irradiation. The whole blood 5-HT and cholinesterase
      levels were evaluated three days before, immediately, and three days after laser
      irradiation. Pain score after treatment decreased to a score of 5.8 corresponding
      to 64% of pain reduction (P < 0.05). LLLT promoted a decrease in the blood flow
      velocity (P < 0.05). In addition, the 5-HT levels were significantly increased
      three days after LLLT (P < 0.05). The cholinesterase levels remained unchanged at
      the analyzed time points (P > 0.05). Our findings indicated that LLLT regulates
      blood flow in the temporal artery after irradiation and might control 5-HT levels
      in patients suffering with tension-type headache associated to TMD contributing
      to pain relief. 

PMID- 26202375
TI  - Dietary 2-oxoglutarate mitigates gastrectomy-evoked structural changes in
      cartilage of female rats.
AB  - Gastrectomy (Gx) leads to osteopenia/osteoporosis in humans and animals. However,
      little is known about the influence of Gx on the cartilage in this regard. Recent
      studies have demonstrated a protective effect of 2-oxoglutaric acid (2-Ox) on
      bone and cartilage. Hence, the purpose of this study was to investigate whether 2
      Ox can mitigate eventual Gx-induced cartilage impairment. Twenty female Sprague
      Dawley rats were subjected to Gx and randomly divided into two groups: Gx + 2-Ox
      and Gx. Another 20 rats were sham-operated (ShO) and randomly divided into two
      groups: ShO + 2-Ox and ShO. The daily dose of 2-Ox administered to the rats in
      the drinking water was 0.43 g per 100 g rat. After eight weeks, rats were
      euthanized and femora and tibiae were collected. Histology and histomorphometry
      analyses of the articular cartilage and the growth plate were done. Gx resulted
      in a 32% (+/-44.5 femur, +/-35.8 tibia) decrease in overall thickness of
      articular cartilage in both bones (femur: ShO 279.1 +/- 48.5 vs. Gx 190.2 +/-
      38.4 um, tibia: ShO 222.9 +/- 50.3 um vs. Gx 151.3 +/- 52.6 um) (in some zones up
      to 58 +/- 28.0%), and in the growth plate up to 20% (+/-22.4) (femur: ShO 243.0
      +/- 34.0 vs. Gx 207.0 +/- 33.7 um, tibia: ShO 220.0 +/- 24.6 um vs. Gx 171.1 +/-
      16.1 um). Gx altered the spatial distribution of thick and thin collagen fibers,
      and chondrocyte shape and size. 2-Ox administration prevented the reduction in
      both cartilages thickness (Gx + 2-Ox: articular cartilage 265.2 +/- 53.8 um,
      235.6 +/- 42.7 um, growth plate 236.7 +/- 39.2 um, 191.3 +/- 16.5 um in femur and
      tibia, respectively), and abolished the spatial changes in collagen distribution
      and structure induced by Gx. Gx affects cartilage structure and thickness,
      however, 2-Ox administration mitigates these effects and showed protective and
      stimulatory properties. Our observations suggest that dietary 2-Ox can be used to
      offset some of the changes in hyaline cartilage, in particular articular
      cartilage, following bariatric surgeries. 

PMID- 26202376
TI  - Opioid growth factor and low-dose naltrexone impair central nervous system
      infiltration by CD4 + T lymphocytes in established experimental autoimmune
      encephalomyelitis, a model of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system
      (CNS), characterized by infiltrating myelin-reactive T lymphocytes and
      demyelinating lesions. Experimental autoimmune encephalomyelitis (EAE) is the
      animal model widely utilized to study MS. EAE is mediated by CD4(+) T cells and
      can be induced in EAE-susceptible mice through immunization with a myelin
      antigen, such as proteolipid protein 139-151 (PLP139-151) in SJL mice. In this
      PLP-induced EAE model, autoreactive CD4(+) T cells migrate from peripheral
      tissues into the CNS where they are reactivated resulting in CNS damage. Th1 and
      Th17 cells produce the pro-inflammatory cytokines IFNgamma and IL-17,
      respectively, that have been shown to have pathogenic roles in EAE and MS. Anti
      inflammatory Th2, IL-4 secreting cells, have been indicated to inhibit EAE
      exacerbation. However, given the inflammatory environment of EAE, Th2 effector
      cells are outnumbered by Th1/Th17 cells. Regulatory CD4(+) T cells suppress
      immune reactions and have been demonstrated to be dysfunctional in MS patients.
      Opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin, is a negative
      growth factor that interacts with the OGF receptor. The OGF-OGFr axis can be
      activated through exogenous administration of OGF or a low dosage of naltrexone
      (LDN), an opioid antagonist. We have previously demonstrated that modulation of
      the OGF-OGFr axis results in alleviation from relapse-remitting EAE, and that CNS
      infiltrating CD3(+) T cells are diminished with exogenous OGF or intermittent
      blockade with LDN administration. In this paper, we aimed to determine whether
      OGF or LDN alter the Th effector responses of CD4(+) T lymphocytes within the CNS
      in established EAE. We report in these studies that the numbers of CD4(+) T
      lymphocytes in the CNS of EAE mice are decreased following treatment with OGF for
      five days but not LDN. However, modulation of the OGF-OGFr axis did not result in
      changes to CD4(+) Th effector cell responses in the CNS of EAE mice. 

PMID- 26202377
TI  - MicroRNAs predict and modulate responses to chemotherapy in colorectal cancer.
AB  - Colorectal cancer (CRC) is the fourth leading cause of cancer-related death
      globally. Chemotherapy regimens consisting of 5-fluorouracil (5-FU) in
      combination with either oxaliplatin or irinotecan are the first-line options for
      treatment of metastatic CRC. However, primary or acquired resistance to these
      chemotherapeutics is a major clinical challenge. MicroRNAs (miRNAs) are a group
      of small non-coding RNAs that regulate gene expression post-transcriptionally.
      miRNAs play important roles in many cancer-related processes, including cell
      proliferation, apoptosis and invasion, and their dysregulation is implicated in
      colorectal tumourigenesis. Pertinent to chemotherapy, increasing evidence has
      revealed that miRNAs can be directly linked to chemosensitivity in CRC. In this
      review, we summarize current evidence concerning the role of miRNAs in prediction
      and modulation of cellular responses to 5-FU, oxaliplatin and irinotecan in CRC.
      We also discuss the possible targets and intracellular pathways involved in these
      processes. 

PMID- 26202378
TI  - Bone reactions around dental implants subjected to progressive static load: an
      experimental study in dogs.
AB  - OBJECTIVE: To evaluate histologically and histomorphometrically, the peri-implant
      bone reaction around implants subjected to controlled progressive orthodontic
      loading. MATERIALS AND METHODS: In three beagle dogs, bilateral edentulous flat
      alveolar ridges were created in the maxillary area posterior to the canines.
      After 8 weeks of healing, 24 implants (Biomet 3i) were inserted in the edentulous
      sites. Two experimental groups were created. Progressive loading group: Twelve
      implants were left to heal for 8 weeks uncovered, and abutments were adapted and
      connected by pairs with Ni-Ti orthodontic springs. A gradual static force of 100,
      200 and 300 g was applied for a 3-week period each. Thus, a total progressive
      loading period of 9 weeks was exercised. Unloaded control group: Twelve implants
      were left to heal undisturbed. At the end of the experimental period, all
      implants of both groups were removed with the surrounding bone. Histologic and
      histomorphometric analyses were performed, and the following parameters were
      measured: bone-to-implant contact, bone density 1 and 2 mm distant to the implant
      threads and crestal bone resorption. Median regression models are used for
      statistical analysis. RESULTS: Implants of the progressive loading group
      exhibited significantly higher percentage of bone-to-implant contact compared to
      the unloaded control implants (P = 0.018). Bone density 1 and 2 mm distant to the
      threads was found to be the same between the two groups (P = 0.734 and P = 0.961,
      respectively). Crestal bone resorption did not differ between loaded and unloaded
      implants (P = 0.813). CONCLUSION: The application of progressive loading by
      controlled orthodontic force on osseointegrated implants provoked significant
      increase in the percentage of bone-to-implant contact of the low-density bone of
      the dog maxilla.

PMID- 26202379
TI  - COMPUTED TOMOGRAPHIC, RADIOGRAPHIC, AND ENDOSCOPIC TRACHEAL DIMENSIONS IN ENGLISH
      BULLDOGS WITH GRADE 1 CLINICAL SIGNS OF BRACHYCEPHALIC AIRWAY SYNDROME.
AB  - Tracheal hypoplasia is commonly seen in English Bulldogs affected with
      brachycephalic airway syndrome. Previously published diagnostic criteria for
      tracheal hypoplasia in this breed have been a radiographic tracheal
      diameter:tracheal inlet ratio (TD:TI) < 0.12 or a tracheal diameter:third rib
      diameter ratio (TD:3R) < 2.0. Computed tomography has become increasingly used
      for airway evaluation, however published information is lacking regarding CT
      tracheal dimensions in English Bulldogs. Objectives of this prospective cross
      sectional study were to describe radiographic and CT tracheal dimensions in a
      sample of clinically normal English Bulldogs and compare these values with
      tracheoscopy scores. Computed tomography (n = 40), radiography (n = 38), and
      tracheoscopy (n = 40) studies were performed during a single general anesthesia
      session for each included dog. Tracheal measurements were recorded at three
      locations: cervical, thoracic inlet, and thorax. Tracheal diameters were
      narrowest at the thoracic inlet with all techniques. Computed tomographic
      measurements averaged 19% greater than radiographic measurements. All included
      dogs had radiographic tracheal measurements greater than the previously published
      criteria for tracheal hypoplasia. Mean CT TD:TI was 0.26 (+/- 0.03, 0.20-0.33),
      and mean CT TT:3R was 2.27 (+/- 0.24, 1.71-2.74). Radiographic TD:TI and CT TD:TI
      were significantly correlated (P = 0.00); however radiographic TT:3R and CT TT:3R
      were not significantly correlated (P = 0.25). Tracheoscopy identified hypoplastic
      changes in all dogs and tracheoscopy scores were not correlated with CT or
      radiography diameter measurements. In conclusion, findings indicated that some CT
      and radiographic tracheal diameter measurements were comparable in English
      Bulldogs however diameters for both imaging techniques were not comparable with
      tracheoscopy scores. 

PMID- 26202380
TI  - Overexpression of CD55 from Barrett's esophagus is associated with esophageal
      adenocarcinoma risk.
AB  - BACKGROUND AND AIM: Although several molecular biomarkers for esophageal
      adenocarcinoma (EAC) have been shown to be useful disease indicators, none has
      been established as a reliable indicator for risk of EAC or have progressed to
      routine use. The aim was to identify biomarkers of high risk for EAC in patients
      with Barrett's esophagus (BE). METHODS: Following endoscopic observation by
      magnified endoscopy with narrow band imaging (ME-NBI), brushing was followed by
      obtaining biopsy samples from columnar-lined esophagus (CLE) and from EAC lesions
      of EAC patients, and from age- and sex-matched non-EAC controls with BE. Total
      RNA was extracted for microarray analysis using Affymetrix GeneChip Human Genome
      U133 plus 2.0 Array. Real-time-PCR analysis of identified candidate genes was
      used to confirm the results. RESULTS: Overall, 9 EAC patients and 50 patients
      with BE were studied. Seventy-nine candidate genes were identified by microarray
      analysis based on a proportional hazards model (P < 0.005). Six genes exhibited
      significantly differential expressions in both BE and cancer lesions of the EAC
      group compared to BE of the controls. In the brushing samples, median CD55
      relative expression levels in cancer lesions were highest and decreased in BE of
      EAC group and BE of the controls, in that order (P < 0.001). CONCLUSION: Over
      expression of CD55 in brushing samples taken from BE may be associated with the
      risk of EAC.

PMID- 26202382
TI  - Compassionate use of experimental therapies: who should decide?

PMID- 26202381
TI  - High levels of cyclic-di-GMP in plant-associated Pseudomonas correlate with
      evasion of plant immunity.
AB  - The plant innate immune system employs plasma membrane-localized receptors that
      specifically perceive pathogen/microbe-associated molecular patterns
      (PAMPs/MAMPs). This induces a defence response called pattern-triggered immunity
      (PTI) to fend off pathogen attack. Commensal bacteria are also exposed to
      potential immune recognition and must employ strategies to evade and/or suppress
      PTI to successfully colonize the plant. During plant infection, the flagellum has
      an ambiguous role, acting as both a virulence factor and also as a potent
      immunogen as a result of the recognition of its main building block, flagellin,
      by the plant pattern recognition receptors (PRRs), including FLAGELLIN SENSING2
      (FLS2). Therefore, strict control of flagella synthesis is especially important
      for plant-associated bacteria. Here, we show that cyclic-di-GMP [bis-(3'-5')
      cyclic di-guanosine monophosphate], a central regulator of bacterial lifestyle,
      is involved in the evasion of PTI. Elevated cyclic-di-GMP levels in the pathogen
      Pseudomonas syringae pv. tomato (Pto) DC3000, the opportunist P. aeruginosa PAO1
      and the commensal P. protegens Pf-5 inhibit flagellin synthesis and help the
      bacteria to evade FLS2-mediated signalling in Nicotiana benthamiana and
      Arabidopsis thaliana. Despite this, high cellular cyclic-di-GMP concentrations
      were shown to drastically reduce the virulence of Pto DC3000 during plant
      infection. We propose that this is a result of reduced flagellar motility and/or
      additional pleiotropic effects of cyclic-di-GMP signalling on bacterial
      behaviour. 

PMID- 26202383
TI  - Update on the Methodological Quality of Research Published in The American
      Journal of Sports Medicine: Comparing 2011-2013 to 10 and 20 Years Prior.
AB  - BACKGROUND: In recent years, the number of articles in The American Journal of
      Sports Medicine (AJSM) has risen dramatically, with an increasing emphasis on
      evidence-based medicine in orthopaedics and sports medicine. HYPOTHESIS: Despite
      the increase in the number of articles published in AJSM over the past decade,
      the methodological quality of articles in 2011-2013 has improved relative to
      those in 2001-2003 and 1991-1993. STUDY DESIGN: Meta-analysis. METHODS: All
      articles published in AJSM during 2011-2013 were reviewed and classified by study
      design. For each article, the use of pertinent methodologies, such as prospective
      data collection, randomization, control groups, and blinding, was recorded. The
      frequency of each article type and the use of evidence-based techniques were
      compared relative to 1991-1993 and 2001-2003 by use of Pearson chi(2) testing.
      RESULTS: The number of research articles published in AJSM more than doubled from
      402 in 1991-1993 and 423 in 2001-2003 to 953 in 2011-2013. Case reports decreased
      from 15.2% to 10.6% to 2.1% of articles published over the study period (P <
      .001). Cadaveric/human studies and meta-analysis/literature review studies
      increased from 5.7% to 7.1% to 12.4% (P < .001) and from 0.2% to 0.9% to 2.3% (P
      = .01), respectively. Randomized, prospective clinical trials increased from 2.7%
      to 5.9% to 7.4% (P = .007). Fewer studies used retrospective compared with
      prospective data collection (P < .001). More studies tested an explicit
      hypothesis (P < .001) and used controls (P < .001), randomization (P < .001), and
      blinding of those assessing outcomes (P < .001). Multi-investigator trials
      increased (P < .001), as did the proportion of articles citing a funding source
      (P < .001). CONCLUSION: Despite a dramatic increase in the number of published
      articles, the research published in AJSM shifted toward more prospective,
      randomized, controlled, and blinded designs during 2011-2013 compared with 2001
      2003 and 1991-1993, demonstrating a continued improvement in methodological
      quality.

PMID- 26202384
TI  - From Fragmentation to Construction--from Void to Massive: Fascination with
      Organic Mass Spectrometry and the Synthesis of Novel Three-Dimensional Polycyclic
      Aromatic Hydrocarbons.
AB  - Detailed insights gained from our research into the gas-phase chemistry of
      ionized and protonated diphenylalkanes and their congeners, obtained by extended
      synthesis of isotopically labeled model compounds and mass spectrometry, are
      presented and merged with those acquired during our development of a new family
      of polycyclic hydrocarbons, the centropolyindanes. Aside from a Personal Account
      that describes "two scientific lives in one", it is demonstrated, on the one
      hand, how our understanding of organic chemistry can help to shed light on the
      details of mass spectrometric fragmentation and to unravel, in a more fundamental
      way, the unimolecular reactivity of gaseous ions. On the other hand, it is shown
      how unexpected reactivity of related ions in solution, being subject to the very
      same fundamentals of organic chemistry, can lead to the construction of novel
      and, in part, unique three-dimensional polycyclic structures that may contribute
      to future research in material science. Two such apparently independent fields of
      organic chemistry may be seen as joint contributions of the art of science. 

PMID- 26202386
TI  - Pyoderma gangrenosum and Sweet syndrome: the prototypic neutrophilic dermatoses.
AB  - Pyoderma gangrenosum, a dramatic ulcerative skin disease, and Sweet syndrome, a
      papular dermatosis, were described independently. It was subsequently shown that
      they share many characteristics, including clinical overlap and the frequent
      association with multisystemic disorders. The group of the neutrophilic
      dermatoses encompasses these two dermatoses, as well as other conditions having
      in common an aseptic neutrophilic infiltrate predominating in the epidermis
      and/or the dermis and/or the subcutis. Some patients also experience neutrophilic
      infiltrates in other organs, defining the neutrophilic disease. Recent research
      suggests that the neutrophilic dermatoses could be considered as the cutaneous
      expression of the autoinflammation, an aberrant hyperproduction of interleukin-1.
      Autoinflammation is responsible for monogenic diseases, and is also involved in
      the mechanism of many polygenic conditions, including the neutrophilic
      dermatoses.

PMID- 26202385
TI  - Photoreactive Polymers Bearing a Zwitterionic Phosphorylcholine Group for Surface
      Modification of Biomaterials.
AB  - Photoreactive polymers bearing zwitterionic phosphorylcholine and benzophenone
      groups on the side chain were synthesized and used as surface modification
      reagents for biomaterials. A photoreactive methacrylate containing the
      benzophenone group, 3-methacryloyloxy-2-hydroxypropyl-4-oxybenzophenone (MHPBP),
      was synthesized via a ring-opening and addition reaction between glycidyl
      methacrylate and 4-hydroxybenzophenone. Then, water-soluble, amphiphilic polymers
      poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-MHPBP) (PMH) and poly(MPC
      co-n-butyl methacrylate-co-MHPBP), with different monomer unit compositions, were
      synthesized through radical polymerization. Ultraviolet-visible (UV/vis)
      absorption spectra of these polymer solutions showed that these polymers have
      maximum absorption peaks at 254 and 289 nm that can be attributed to the
      benzophenone unit. The intensity of UV adsorption at 289 nm was decreased with
      increased UV irradiation time, and it was saturated within a few minutes,
      indicating that the polymers are highly sensitive to UV irradiation. A commercial
      material (i.e., cyclic polyolefin) was simply modified by a UV irradiation for
      1.0 min. Fourier transform infrared spectroscopy and X-ray photoelectron
      spectroscopy analysis results indicated that the stability of the polymer on the
      surface was dramatically enhanced because of the photochemical reaction of the
      benzophenone moiety. The air contact angles of PMH surfaces measured in water
      were up to 160 degrees . Thus, highly hydrophilic surfaces were obtained. The
      critical surface tension of the PMH-modified surface was 45.7 mN/m. By evaluating
      the biological reactivity of the treated surface, protein adsorption and cell
      adhesion were completely inhibited on the surface, which was prepared using a
      photopatterning procedure using PMH. In conclusion, photoreactive MPC polymers
      with a benzophenone moiety could be used as a novel and effective surface
      modifier. 

PMID- 26202388
TI  - Endovascular Management of Acute Embolic Occlusion of the Superior Mesenteric
      Artery: A 12-Year Single-Centre Experience.
AB  - PURPOSE: Retrospective evaluation of 12-year experience with endovascular
      management of acute mesenteric ischemia (AMI) due to embolic occlusion of the
      superior mesenteric artery (SMA). MATERIALS AND METHODS: From 2003 to 2014, we
      analysed the in-hospital mortality of 37 patients with acute mesenteric embolism
      who underwent primary endovascular therapy with subsequent on-demand laparotomy.
      Transcatheter embolus aspiration was used in all 37 patients (19 women, 18 men,
      median age 76 years) with embolic occlusion of the SMA. Adjunctive local
      thrombolysis (n = 2) and stenting (n = 2) were also utilised. RESULTS: We
      achieved complete recanalization of the SMA stem in 91.9 %. One patient was
      successfully treated by surgical embolectomy due to a failed endovascular
      approach. Subsequent exploratory laparotomy was performed in 73.0 % (n = 27), and
      necrotic bowel resection in 40.5 %. The total in-hospital mortality was 27.0 %.
      CONCLUSION: Primary endovascular therapy for acute embolic SMA occlusion with on
      demand laparotomy is a recommended algorithm used in our centre to treat SMA
      occlusion. This combined approach for the treatment of AMI is associated with in
      hospital mortality rate of 27.0 %.

PMID- 26202387
TI  - Retinal histopathology in eyes from patients with autosomal dominant retinitis
      pigmentosa caused by rhodopsin mutations.
AB  - PURPOSE: To evaluate the histopathology in donor eyes from patients with
      autosomal dominant retinitis pigmentosa (ADRP) caused by p.P23H, p.P347T and
      p.P347L rhodopsin ( RHO ) gene mutations. METHODS: Eyes from a 72-year-old male
      (donor 1), an 83-year-old female (donor 2), an 80-year-old female (donor 3), and
      three age-similar normal eyes were examined macroscopically, by scanning laser
      ophthalmoscopy and optical coherence tomography imaging. Perifoveal and
      peripheral pieces were processed for microscopy and immunocytochemistry with
      markers for photoreceptor cells. RESULTS: DNA analysis revealed RHO mutations
      c.68C>A (p.P23H) in donor 1, c.1040C>T (p.P347L) in donor 2 and c.1039C>A
      (p.P347T) in donor 3. Histology of the ADRP eyes showed retinas with little
      evidence of stratified nuclear layers in the periphery and a prominent inner
      nuclear layer present in the perifoveal region in the p.P23H and p.P347T eyes,
      while it was severely atrophic in the p.P347L eye. The p.P23H and p.P347T
      mutations cause a profound loss of rods in both the periphery and perifovea,
      while the p.P347L mutation displays near complete absence of rods in both
      regions. All three rhodopsin mutations caused a profound loss of cones in the
      periphery. The p.P23H and p.P347T mutations led to the presence of highly
      disorganized cones in the perifovea. However, the p.P347L mutation led to near
      complete absence of cones also in the perifovea. CONCLUSIONS: Our results support
      clinical findings indicating that mutations affecting residue P347 develop more
      severe phenotypes than those affecting P23. Furthermore, our results indicate a
      more severe phenotype in the p.P347L retina as compared to the p.P347T retina.

PMID- 26202389
TI  - Mid-Term Outcomes of Endovascular Treatment for TASC-II D Femoropopliteal
      Occlusive Disease with Critical Limb Ischemia.
AB  - PURPOSE: The purpose of the study was to assess the safety and midterm
      effectiveness of endovascular treatment in Trans-Atlantic Inter-Society Consensus
      II (TASC-II) D femoropopliteal occlusions in patients with critical limb ischemia
      (CLI). METHODS: Patients with CLI who underwent endovascular treatment for TASC-D
      de novo femoropopliteal occlusive disease between September 2008 and December
      2013 were selected. Data included anatomic features, pre- and postprocedure ankle
      brachial index, duplex ultrasound, and periprocedural complications. Sustained
      clinical improvement, limb salvage rate, freedom from target lesion
      revascularization (TLR), and freedom from target extremity revascularization
      (TER) were assessed by Kaplan-Meier estimation and predictors of
      restenosis/occlusion with Cox analysis. RESULTS: Thirty-two patients underwent
      treatment of 35 TASC-D occlusions. Mean age was 76 +/- 9. Mean lesion length was
      23 +/- 5 cm. Twenty-eight limbs (80 %) presented tissue loss. Seventeen limbs
      underwent treatment by stent, 13 by stent-graft, and 5 by angioplasty. Mean
      follow-up was 29 +/- 20 months. Seven patients required major amputation and six
      patients died during follow-up. Eighteen endovascular and three surgical TLR
      procedures were performed due to restenosis or occlusion. Estimated freedom from
      TLR and TER rates at 2 years were 41 and 76%, whereas estimated primary and
      secondary patency rates were 41 and 79%, respectively. CONCLUSIONS: Endovascular
      treatment for TASC II D lesions is safe and offers satisfying outcomes. This
      patient subset would benefit from a minimally invasive approach. Follow-up is
      advisable due to a high rate of restenosis. Further follow-up is necessary to
      know the long-term efficacy of these procedures.

PMID- 26202390
TI  - Successful Radiofrequency Guidewire Recanalization of a Chronic Portal Vein
      Occlusion That Failed Conventional Therapy.

PMID- 26202392
TI  - Severe Adverse Reaction During DMSO Injection for Onyx Embolization of a Thoracic
      Type II Endoleak.

PMID- 26202391
TI  - Peripherally Inserted Central Catheter-Related Infections in a Cohort of
      Hospitalized Adult Patients.
AB  - PURPOSE: To determine the incidence and the risks factors of peripherally
      inserted central catheter (PICC)-related infectious complications. MATERIALS AND
      METHODS: Medical charts of every in-patient that underwent a PICC insertion in
      our hospital between January 2010 and October 2013 were reviewed. All PICC
      related infections were recorded and categorized as catheter-related bloodstream
      infections (CR-BSI), exit-site infections, and septic thrombophlebitis. RESULTS:
      Nine hundred and twenty-three PICCs were placed in 644 unique patients, mostly
      male (68.3%) with a median age of 58 years. 31 (3.4%) PICC-related infections
      occurred during the study period corresponding to an infection rate of 1.64 per
      1000 catheter-days. We observed 27 (87.1%) CR-BSI, corresponding to a rate of
      1.43 per 1000 catheter-days, 3 (9.7%) septic thrombophlebitis, and 1 (3.2%) exit
      site infection. Multivariate logistic regression analysis showed a higher PICC
      related infection rate with chemotherapy (odds ratio (OR) 7.2-confidence interval
      (CI) 95% [1.77-29.5]), auto/allograft (OR 5.9-CI 95% [1.2-29.2]), and anti
      coagulant therapy (OR 2.2-95% [1.4-12]). CONCLUSION: Chemotherapy,
      auto/allograft, and anti-coagulant therapy are associated with an increased risk
      of developing PICC-related infections. CLINICAL ADVANCE: Chemotherapy,
      auto/allograft, and anti-coagulant therapy are important predictors of PICC
      associated infections. A careful assessment of these risk factors may be
      important for future success in preventing PICC-related infections.

PMID- 26202393
TI  - ChEVAS: Combining Suprarenal EVAS with Chimney Technique.
AB  - Endovascular sealing with the Nellix((r)) endoprosthesis (EVAS) is a new
      technique to treat infrarenal abdominal aortic aneurysms. We describe the use of
      endovascular sealing in conjunction with chimney stents for the renal arteries
      (chEVAS) in two patients, one with a refractory type Ia endoleak and an expanding
      aneurysm, and one with a large juxtarenal aneurysm unsuitable for fenestrated
      endovascular repair (EVAR). Both aneurysms were successfully excluded. Our report
      confirms the utility of chEVAS in challenging cases, where suprarenal seal is
      necessary. We suggest that, due to lack of knowledge on its durability, chEVAS
      should only been considered when more conventional treatment modalities (open
      repair and fenestrated EVAR) are deemed difficult or unfeasible. 

PMID- 26202394
TI  - What is the best surgical intervention for stress urinary incontinence in the
      very young and very old? An International Consultation on Incontinence Research
      Society update.
AB  - An increasing number of continence procedures are being performed in women of all
      ages. An overview of the existing literature and consensus regarding surgery for
      stress urinary incontinence (SUI) in the young and the old was presented and
      discussed at the International Consultation on Incontinence Research Society
      Think Tank. This manuscript reflects the Think Tank's summary and opinion.
      Despite the increasing number of continence procedures, there are relatively few
      data to guide management in the very young and the very old. When considering
      continence surgery in the young, long-term efficacy and safety are paramount, and
      the future effects of pregnancy and childbirth need to be carefully considered.
      Conversely, in the elderly, minimally invasive procedures with low morbidity are
      important, especially in the frail elderly who may have significant co
      morbidities. Further research including prospective randomised trials, cohort
      studies and national registries, should help guide our management in these two
      challenging groups of patients. 

PMID- 26202395
TI  - Influence of lymphatic endothelial cells on proliferation and invasiveness of
      esophageal carcinoma cells in vitro and lymphangiogenesis in vivo.
AB  - The aim of the study was to investigate the interaction between esophageal
      carcinoma cells with different differentiation degree and esophageal carcinoma
      related lymphatic endothelial cells. Different lymphatic endothelial cell
      conditioned mediums were used to cultivate well-differentiated esophageal
      carcinoma EC9706 cells and poorly differentiated esophageal carcinoma KYSE150
      cells, and immunocytochemistry and Western blot analyses were applied to detect
      the expression of MMP-9 protein and TIMP-2 protein in each group; in situ
      hybridization and RT-PCR methods were used to detect the expression of MMP-9 and
      TIMP-2 mRNA in each group; CCK-8 method was used to detect cell proliferation in
      each group; and transwell method was utilized to detect cell invasiveness in each
      group. Through constructing the transplanted tumor model of esophageal carcinoma
      of nude mice, the D2-40 and LYVE-1 immunohistochemical staining was performed on
      transplanted tumors and surrounding tissues, lymphatic microvessels were marked,
      and lymphatic microvessel density (LMVD) was measured. The expression of MMP-9
      protein and mRNA in experimental group was significantly higher than that in
      control groups (P < 0.05); TIMP-2 protein and mRNA expression in experimental
      group was significantly lower than that in control groups (P < 0.05); cell
      proliferation ability and invasiveness ability in experimental group were
      significantly higher than those in control groups (P < 0.05); LMVD-marked D2-40
      and LMVD-marked LYVE-1 of transplanted tumor tissue in the experimental group
      were significantly higher than those in control groups (P < 0.05). The esophageal
      squamous carcinoma-related lymphatic microvessel could promote the proliferation
      and invasive ability of esophageal squamous carcinoma cells in vitro. It had
      different effects on esophageal carcinoma cells with different differentiation
      degree and had more obvious influence on poorly differentiated esophageal
      carcinoma cells, which may be related to the up-regulated MMP-2 expression and
      down-regulated TIMP-2 expression of esophageal carcinoma cells. The esophageal
      squamous carcinoma-related lymphatic microvessel endothelial cells could promote
      the growth of esophageal carcinoma-transplanted tumor of nude mice and
      lymphangiogenesis. 

PMID- 26202397
TI  - The value of the thromboelastometry heparinase assay (HEPTEM) in cardiac surgery.
AB  - The thromboelastometry INTEM clotting time (CT) with heparinase (HEPTEM) is
      frequently used to detect residual heparin after cardiopulmonary bypass (CPB) in
      cardiac surgery. This study investigated whether the HEPTEM CT reflects the
      presence of residual heparin and the association of the protamine-to-heparin
      ratio to the INTEM and HEPTEM CT. We retrospectively evaluated thromboelastometry
      data that were obtained before CPB and after protamine infusion following CPB in
      two tertiary hospitals. The number of patients with an INTEM: HEPTEM ratio (IH
      ratio) > 1, suggesting residual heparin, were quantified. Moreover, the influence
      of different protamine-to-heparin-dosing-ratios (P:H) on the INTEM and HEPTEM CT
      was evaluated in the clinical setting and in blood drawn from healthy volunteers.
      An INTEM: HEPTEM CT ratio > 1.1 was observed in 16 % of the patients prior to
      CPB, and in 15 % after protamine administration. Interestingly, 23 % and 36 % of
      the patients had an HEPTEM CT exceeding the INTEM CT before CPB and following
      protamine administration. The HEPTEM CT was longer than the INTEM CT in patients
      with a P:H-ratio of 1:1 (265 +/- 132 vs 260 +/- 246 s; p=0.002) or P:H-ratio of
      1.3:1 (357 +/- 174 vs 292 +/- 95 s; p=0.001). Increasing P:H-ratios induced a
      prolonged HEPTEM CT in fresh blood. In conclusion, limited agreement was observed
      between INTEM and HEPTEM clotting time in the absence of heparin. INTEM
      comparison to HEPTEM may not always reliably reflect the presence of residual
      heparin, while protamine may additionally affect the latter test. These
      observations complicate HEPTEM results interpretation in clinical situations with
      suspected residual heparin effect after protamine.

PMID- 26202396
TI  - Characterization of the honeybee AmNaV1 channel and tools to assess the toxicity
      of insecticides.
AB  - Pollination is important for both agriculture and biodiversity. For a significant
      number of plants, this process is highly, and sometimes exclusively, dependent on
      the pollination activity of honeybees. The large numbers of honeybee colony
      losses reported in recent years have been attributed to colony collapse disorder.
      Various hypotheses, including pesticide overuse, have been suggested to explain
      the disorder. Using the Xenopus oocytes expression system and two microelectrode
      voltage-clamp, we report the functional expression and the molecular,
      biophysical, and pharmacological characterization of the western honeybee's
      sodium channel (Apis Mellifera NaV1). The NaV1 channel is the primary target for
      pyrethroid insecticides in insect pests. We further report that the honeybee's
      channel is also sensitive to permethrin and fenvalerate, respectively type I and
      type II pyrethroid insecticides. Molecular docking of these insecticides revealed
      a binding site that is similar to sites previously identified in other insects.
      We describe in vitro and in silico tools that can be used to test chemical
      compounds. Our findings could be used to assess the risks that current and next
      generation pesticides pose to honeybee populations. 

PMID- 26202398
TI  - Preliminary insight into the periostin leverage during periodontal tissue
      healing.
AB  - BACKGROUND: Tissue repair and regeneration is assisted by the efficient
      coordination of cell and extracellular matrix interactions mediated by
      matricellular molecules such as periostin. Given its high expression around the
      teeth, the periodontal organ represents an ideal system to capture the protein
      dynamics during wound healing. METHODS: An observational prospective case-control
      study was designed to characterize periostin changes over time after periodontal
      surgery in tissue, oral fluids and serum by histological, protein and mRNA
      analyses. RESULTS: Histological analysis showed lower periostin with a diffuse
      local distribution pattern in disease patients. Levels of periostin in gingival
      crevicular fluid (GCF) increased over time for both groups, more noticeably in
      the periodontitis subjects. A transient and subtle change in circulating
      periostin levels was also noticed. The mRNA periostin levels contrasted with the
      protein levels and may indicate the underlying post-transcriptional regulatory
      process during chronic inflammation. Levels of known periodontal disease
      biomarkers such as IL-beta, IL1-alpha, TNF-alpha, MIP-1alpha and CRP served as
      tissue stability markers and complemented the clinical parameters recorded.
      CONCLUSION: The transient local increase in GCF periostin after eliminating the
      local etiology in periodontally affected sites suggests its importance in the
      maturation and stability of the connective tissue. The decreasing levels observed
      as the tissue healed highlight its spatial/temporal significance.

PMID- 26202399
TI  - Tamibarotene: a new hope for therapeutic efficacy in hepatocellular carcinoma
      patients.

PMID- 26202400
TI  - The challenges of novel contrast agents for the imaging diagnosis of
      hepatocellular carcinoma.

PMID- 26202401
TI  - Balance lost: T cell immunity in progressive HBV infection.

PMID- 26202402
TI  - Speckle tracking echocardiography in cirrhosis: is it ready for prime time?

PMID- 26202403
TI  - Long-term culture of primary hepatocytes: new matrices and microfluidic devices.
AB  - Prediction of in vivo drug-induced hepatotoxicity by in vitro cell culture
      systems is still one of the main challenges in drug development. To date, most in
      vitro approaches are based on monolayer cultures of primary hepatocytes, although
      it is known that they rapidly lose their morphology and liver-specific functions,
      such as activities of drug-metabolizing enzymes and transporters. Hepatocyte
      dedifferentiation can be delayed by culturing cells in a 3D environment.
      Combination with continuous medium flow, which creates a more physiological
      situation, further improves the maintenance of hepatic functions. Here, we
      present recently developed hydrogels and scaffolds for 3D culture of hepatocytes,
      which aim at preserving hepatic morphology and functionality for up to 4 weeks in
      culture. Furthermore, major benefits and drawbacks of microfluidic devices for in
      vitro hepatotoxicity screening are discussed. Although promising advances have
      been made regarding the preservation of hepatic functions in 3D flow culture,
      major issues, such as expensive equipment, large cell numbers and low throughput,
      are still hampering their use in drug toxicity screening. For these devices to be
      applied and accepted in the drug-developing industry, it is necessary to combine
      easily accessible matrices that highly preserve the activities of drug
      metabolizing enzymes with a user-friendly microfluidic platform, thereby finding
      the right balance between reflecting the in vivo situation and enabling
      satisfying throughput for drug candidate screening. 

PMID- 26202404
TI  - Advancements in in vitro hepatic models: application for drug screening and
      therapeutics.
AB  - The liver is one of the most complex organs in the body, performing a multitude
      of functions. Liver tissue engineering is a combination of various strategies
      that aim at generating functional liver tissue that can help restore and/or
      support the ailing liver as it recuperates. Conventionally, in vitro culture has
      involved growing cells in different media compositions or layering them on
      matrices largely composed of native ECM components such as collagen or Matrigel.
      With recent advances in technology, more sophisticated techniques are being
      devised that are better equipped to capture distinct features of the liver in an
      in vivo microenvironment. Three-dimensional (3D) cultures of liver cells in 3D
      scaffolds, as spheroids or cell sheets, allow for a high degree of cell-cell and
      cell-matrix interaction and an in vivo-like architecture. More recently,
      decellularized matrices have been used as scaffolds that support ideal cell
      matrix interactions. Microfabrication technologies initially used to pattern
      semiconductors in the integrated circuit industry have grown out of this field
      and now encompass a variety of methods to etch patterns onto both 2D and 3D
      scaffolds to allow incorporation of custom-made features resembling the fluid
      network and organization in native liver. This improvisation permits for enhanced
      vascularization and oxygen diffusion to the in vitro liver tissue. In this
      review, we discuss the various configurations that have been implemented in the
      in vitro culture of liver cells and their application in liver therapeutics in
      the form of implantable liver tissue constructs and tools for drug screening. 

PMID- 26202406
TI  - The co-inhibitory pathway and cellular immune imbalance in the progress of HBV
      infection.
AB  - OBJECTIVE: Chronic hepatitis B (CHB) affects 400 million people and is the most
      common cause of liver cirrhosis (LC) and hepatocellular carcinoma (HCC)
      worldwide. Cellular immune regulation plays an important role in determining the
      infection outcome. Co-signal molecules and Th17/Treg were studied to explore
      their association with the progression of HBV infection. METHODS: Ninety-four HBV
      infected patients were categorized into three groups: 31 patients with LC caused
      by CHB, 30 with HCC caused by CHB and 33 with HCC caused by CHB. Co-signal
      molecules, Th17/Treg, and Stat3 and Stat5 were analyzed by flow cytometry.
      RESULTS: CHB patients who progressed to LC or HCC showed a significantly higher
      level of co-inhibitory molecules such as BTLA and PD-1, while there was no
      significant difference in co-stimulatory molecules among LC, HCC and CHB. Stat3
      and Stat5 were significantly increased in LC and HCC compared to CHB patients.
      CONCLUSION: Co-inhibitory molecules play more important roles than co-stimulatory
      molecules. Increased PD-1 and BTLA/HVEM inhibited immune cells and the immune
      process. At the same time activated Stat3 and Stat5 stimulate the key factors in
      differentiation of Th17 and Treg, thus leading to imbalanced expansion of Th17
      and Treg; immune tolerance was induced and HBV persistent. This resulted in
      hepatic inflammation that progressed to cirrhosis and carcinoma.

PMID- 26202405
TI  - Loss of HBsAg and antiviral treatment: from basics to clinical significance.
AB  - Accurate prediction of the sustained virological response (SVR) to antiviral
      therapy against chronic hepatitis B (CHB) is still a crucial problem needing
      profound investigation. In recent years, quantification of hepatitis B surface
      antigen (HBsAg), a reliable predictor of SVR and an ideal endpoint of treatment,
      has attracted increasing attention. Serum HBsAg titer may reflect the level of
      intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in
      most patients, and vary with natural phases of chronic HBV infection, genotypes
      and variants, antiviral therapy, and other related factors. Serum HBsAg <200
      IU/mL or yearly reduction >=0.5 log10IU/mL may be the optimum cut-off values for
      prediction of the chance of spontaneous seroclearance of HBsAg. Serum HBsAg
      <1,000 IU/mL with HBV DNA <2,000 IU/mL may identify most of the inactive HBV
      carriers from active HBeAg(-) hepatitis. Interferon-based therapy can lead to
      more significant HBsAg decline than therapy based on nucleoside and/or nucleotide
      analogues. Different patterns or kinetics of HBsAg decline during therapy are
      related to different probabilities of SVR. A low HBsAg level, <3,000 IU/mL at
      baseline, or HBsAg level, <1,500 IU/mL at week 12, or a rapid on-treatment HBsAg
      decline of >=0.5 log10IU/mL at week 12, may predict higher probability of SVR.
      However these cut-off values must be further validated for larger cohort of
      patients across genotypes worldwide. Incorporation of serum HBsAg level, HBeAg
      status, HBV DNA load, HBV genotypes, and other related factors might help
      establish new concept of more practical "response-guided treatment (RGT)" rules
      for antiviral therapy. 

PMID- 26202407
TI  - Nucleoside analogs prevent disease progression in HBV-related acute-on-chronic
      liver failure: validation of the TPPM model.
AB  - PURPOSE: This study aimed to evaluate the efficacy and safety of entecavir,
      lamivudine and telbivudine for treating patients with HBV-ACLF and to validate
      the Tongji prognostic predictor model (TPPM) in these patients. METHODS: In this
      retrospective study, we enrolled 283 patients with HBV-ACLF (100 treated with
      entecavir, 98 treated with lamivudine and 85 treated with telbivudine). There
      were no significant differences in baseline clinical and virological
      characteristics among patients treated with entecavir, telbivudine or lamivudine.
      RESULTS: There were no significant differences in the 4- and 12-week survival
      rates of entecavir-, telbivudine- and lamivudine-treated patients (79.00, 81.18
      and 86.73 %, respectively, at 4 weeks; 67.00, 65.88 and 73.47 %, respectively, at
      12 weeks). Patients in all three groups achieved an improvement in the model for
      end-stage liver disease (MELD) score. Using the Hosmer-Lemeshow test, the
      validation of the TPPM score for HBV-ACLF demonstrated a good degree of fit with
      disease prognosis. Based on this unique group of patients, the TPPM score with an
      AUC of 0.787 was superior to the MELD score, which had an AUC of 0.736 in the
      prediction of 12-week mortality. The TPPM had an AUC of 0.733, and the MELD score
      had an AUC of 0.672 in the prediction of 4-week mortality. Using a cutoff value
      of 0.22 for 12-week mortality prediction by the TPPM, the positive predictive
      value was 49.66 %, with a negative predictive value of 89.55 %. CONCLUSION:
      Treatment with nucleoside analogs including entecavir, lamivudine and telbivudine
      prevented disease progression and increased the survival of patients with HBV
      ACLF. Validation of the established TPPM scoring system in this study confirmed
      its superior predictive value for HBV-ACLF patients when compared with the MELD
      system.

PMID- 26202408
TI  - Two-year results of a randomized, phase III comparative trial of telbivudine
      versus lamivudine in Chinese patients.
AB  - PURPOSE: The burden of chronic hepatitis B infection is high in China, where
      prevalence exceeds 7 %. This was a randomized, double-blinded, phase III study of
      the efficacy and safety of telbivudine and lamivudine treatment at 104 weeks in
      Chinese patients with chronic hepatitis B. METHODS: Hepatitis B e antigen
      positive (n = 290) and -negative (n = 42) adults with nucleoside analog-naive
      compensated chronic hepatitis B were randomized to receive telbivudine 600 mg/day
      or lamivudine 100 mg/day for 104 weeks. The primary endpoint was reduction from
      baseline in serum hepatitis B virus (HBV) DNA at week 52. Week 104 analyses
      included HBV DNA reductions, undetectable HBV DNA (<300 copies/mL), ALT
      normalization, and e-antigen loss/seroconversion. Efficacy at week 104 was also
      assessed as a function of week 24 HBV DNA. RESULTS: In the intention-to-treat
      population (n = 332) at week 104, telbivudine was superior to lamivudine for
      reduction of HBV DNA [-5.48 vs. -4.00 log10 copies/mL; difference -1.49 log10 (95
      % confidence interval -2.2, -0.8); p < 0.0001], for the proportion with
      undetectable HBV DNA (61.9 vs. 38.5 %; p < 0.0001), for ALT normalization (75.8
      vs. 61.3 %; p = 0.0049), and for e-antigen loss (39.9 vs. 28.2 %; p = 0.0373).
      The cumulative probability of genotypic drug resistance was 15.4 % on telbivudine
      versus 23.6 % on lamivudine through week 104. Early virologic response at week 24
      was associated with improved outcomes at week 104. Adverse events were similar to
      those seen in the GLOBE study. CONCLUSIONS: Telbivudine is superior to lamivudine
      over 2 years of chronic hepatitis B treatment in Chinese patients.

PMID- 26202409
TI  - Predictive value of FIB-4 and APRI versus METAVIR on sustained virologic response
      in genotype 1 hepatitis C patients.
AB  - PURPOSE: Advanced liver fibrosis is a negative predictor of virologic response in
      genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive,
      costly, and carries some risk of complications. METHODS: Using data from the
      prospective, international cohort study PROPHESYS, we assessed two alternative
      noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index
      (APRI), to predict virologic response in CHC patients. RESULTS: CHC genotype 1,
      monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40
      KD)/ribavirin in accordance with country-specific legal and regulatory
      requirements and who had baseline METAVIR, FIB-4, and APRI scores (N = 1,592)
      were included in this analysis. Patients were stratified according to the
      baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C
      virus (HCV) RNA <50 IU/mL] by week 4 of treatment (rapid virologic response) and
      24 weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline
      predictors of SVR were explored by multiple logistic regression, and the strength
      of the association between each fibrosis measure and SVR was evaluated. Both FIB
      4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis.
      The association between FIB-4 and SVR (p < 0.1 * 10(-30)) was stronger than that
      between METAVIR (p = 3.86 * 10(-13)) or APRI (p = 5.48 * 10(-6)) and SVR.
      Baseline factors significantly associated with SVR included male gender, lower
      HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase
      ratio. CONCLUSION: The FIB-4 index provides a valuable, noninvasive measure of
      fibrosis and can be used to predict virologic response in patients treated with
      peginterferon alfa-2a (40  KD)/ribavirin.

PMID- 26202410
TI  - An open-label phase I/II study of tamibarotene in patients with advanced
      hepatocellular carcinoma.
AB  - AIM: Tamibarotene is a synthetic retinoid expected to inhibit tumor-cell
      proliferation and to induce apoptosis by selective interaction with retinoic acid
      receptor alpha/beta. We conducted an open-label phase I/II study to determine the
      maximum tolerated dose (MTD) and recommended dose (RD), and to evaluate the
      pharmacokinetics, efficacy, and safety profiles for advanced hepatocellular
      carcinoma (HCC). METHODS: Patients with histologically confirmed, measurable,
      unresectable HCC of Child-Pugh classification A or B and with no effective
      systemic or local therapies were eligible. In phase I, patients were assigned
      based on the 3 + 3 dose escalation criteria to receive tamibarotene at 8, 12, and
      16 mg/day. The RD determined in phase I was employed for phase II. The planned
      sample size in phase II was 25, including the RD-treated patients in phase I.
      RESULTS: Thirty-six patients were enrolled. No patients experienced dose-limiting
      toxicity (DLT) at 8 mg/day. However, two out of six patients experienced the DLTs
      at 12 mg/day: one experienced thrombosis in a limb vein and pulmonary artery, and
      the other experienced an increase of gamma-GTP. The MTD and RD were determined as
      12 and 8 mg/day, respectively. In phase II, one patient achieved partial
      response, and seven achieved stable disease. The disease control rate was 32 %
      (95 % CI: 15.0-53.5). The following drug-related serious adverse events were
      reported: thrombosis in a limb vein, pulmonary artery, and portal vein;
      interstitial lung disease; and vomiting. CONCLUSIONS: Tamibarotene demonstrated
      the inhibition of tumor cell growth in advanced HCC with acceptable tolerance.

PMID- 26202411
TI  - Hepatocellular carcinoma 20 mm or smaller in cirrhosis patients: early magnetic
      resonance enhancement by gadoxetic acid compared with gadopentetate dimeglumine.
AB  - PURPOSE: To evaluate the differences in enhancement pattern of hepatocellular
      carcinoma (HCC) 20 mm or smaller and enhancement effects of hepatic vessels on
      early dynamic contrast-enhanced magnetic resonance imaging (MRI) obtained with
      gadoxetic acid and gadopentetate dimeglumine in the same patients with cirrhosis.
      METHODS: We reviewed MR images using gadoxetic acid and gadopentetate dimeglumine
      in the same 34 patients with 42 histologically confirmed HCCs (median diameter,
      14.5 mm). The percentage enhancements (PEs) of HCC, the hepatic artery and portal
      vein and relative contrasts (RCs) between HCC and the liver were calculated and
      analyzed statistically. RESULTS: The PEs of HCC, the hepatic artery and portal
      vein were significantly lower for gadoxetic acid in comparison with gadopentetate
      dimeglumine in the arterial phase (p = 0.0256 for HCC, p < 0.0001 for hepatic
      artery) and portal phase (p < 0.0001 for HCC, portal vein). The RC between HCC
      and the liver was significantly lower for gadoxetic acid in comparison with
      gadopentetate dimeglumine in the arterial phase (p = 0.0422), but was not
      significantly different in the portal phase (p = 0.1133). Forty-one of the 42
      (97.62 %) nodules showed arterial hypervascularization. Of these, 31 (75.61 %)
      nodules were hypointense in the portal phase for gadoxetic acid, and 22 (53.66 %)
      were hypointense for gadopentetate dimeglumine (p = 0.038). CONCLUSIONS: Compared
      with gadopentetate dimeglumine, gadoxetic acid-enhanced MRI demonstrated a
      different enhancement pattern of inferior arterial enhancement and was more
      rapidly hypointense in the portal phase for HCC. It showed markedly lower
      enhancement for hepatic artery and portal vein in the patients with cirrhosis.

PMID- 26202413
TI  - Non-alcoholic fatty liver disease in a young multiracial Asian population: a
      worrying ethnic predilection in Malay and Indian males.
AB  - PURPOSE: Previous studies on multiracial Malaysian populations found inordinately
      high prevalence of NAFLD among Malays and Indians. Whether the prevalence of
      NAFLD is different among young adults of different ethnic origins is not known.
      We aimed to determine racial differences in NAFLD in a young multiracial
      Malaysian population and associated factors. METHODS: This was a cross-sectional
      study on medical students from the University of Malaya. Diagnosis of NAFLD was
      by transabdominal ultrasonography and following exclusion of significant alcohol
      intake and other causes of chronic liver disease. RESULTS: Data of 469 subjects
      were analyzed (mean age 23.2 +/- 2.4 years, 40.3 % male). The racial distribution
      was: Chinese 53.9 %, Malay 30.5 % and Indian 15.6 %. The overall prevalence of
      NAFLD was 7.9 %. Subjects with NAFLD were older, had greater BMI and WC, higher
      SBP and DBP, higher FBS, serum TG and LDL levels, and lower serum HDL level. The
      prevalence of NAFLD was higher among males compared to females (17.9 % vs. 3.3 %,
      p < 0.001). The highest prevalence of NAFLD was seen among Indian and Malay males
      at 33.3 and 25.5 %, respectively, compared to Chinese males at 6.8 % (p < 0.001).
      No significant difference was seen among females of different races. Independent
      factors associated with NAFLD were male gender, obesity and hypertriglyceridemia.
      CONCLUSIONS: The difference in prevalence of NAFLD among the different ethnic
      groups can be observed as early as young adulthood. An inordinately high
      prevalence of NAFLD was observed among Malay and Indian males consistent with the
      higher prevalence of obesity in these groups.

PMID- 26202412
TI  - Hepatitis C viral load predicts tumor recurrence after curative resection of
      hepatocellular carcinoma regardless of the genotype of hepatitis C virus.
AB  - PURPOSE: To clarify the prognostic impact of the hepatitis C virus (HCV) genotype
      after curative resection for hepatocellular carcinoma (HCC). METHODS: A total of
      199 patients who underwent a curative hepatic resection for HCV-related HCC were
      reviewed. The clinical outcomes were compared between patients infected with HCV
      genotype 1b (n = 160) and those infected with other genotypes (n = 39). RESULTS:
      With a comparable median HCV viral load (6.0 vs. 5.8 log10 IU/mL, p = 0.17), the
      3-year recurrence-free survival (RFS) rates (25 vs. 20 %, p = 0.65) and the 5
      year overall survival (OS) rates (72 vs. 65 %, p = 0.73) were similar between the
      two groups. A multivariate analysis confirmed that HCV viral load of +1.0 log10
      IU/mL [hazard ratio (HR), 1.48], major vascular invasion (HR, 3.20), recurrent
      tumor (HR, 1.77), and preoperative des-gamma carboxyprothrombin level >40 mAu/mL
      (HR, 1.64) were independent predictors of tumor recurrence, while the HCV
      genotype was not a significant risk factor. When the population was stratified
      according to the HCV viral load, a significant difference was observed in the RFS
      rate for both genotype 1b (p = 0.003) and the other genotypes (p = 0.037) at HCV
      viral load of 5.3 log10 IU/mL. CONCLUSIONS: The HCV genotype does not affect the
      surgical outcomes of patients with HCC. A lower HCV viral load is advantageous
      regardless of the HCV genotype.

PMID- 26202414
TI  - Acute liver failure after amanitin poisoning: a porcine model to detect
      prognostic markers for liver regeneration.
AB  - PURPOSE: Over 90 % of fatal mushroom poisoning occurs after ingestion of amanitin
      containing species. This study aimed to investigate markers indicating
      spontaneous liver regeneration in a porcine acute liver failure (ALF) model after
      alpha-amanitin intoxication. METHODS: German landrace pigs received either 0.15
      mg/kg (n = 5) alpha-amanitin intravenously or 0.35 mg/kg (n = 5) intraportally.
      Pigs were invasively monitored and kept under general anesthesia throughout the
      experiment. Laboratory parameters were analyzed every 8 h. RESULTS: ALF occurred
      in all animals (10/10) 41 +/- 3 h after intoxication. All pigs receiving 0.35
      mg/kg alpha-amanitin and one pig receiving 0.15 mg/kg alpha-amanitin died 57 +/-
      16 h after the primary onset of ALF. Four pigs of the 0.15 mg/kg intoxication
      group recovered spontaneously from ALF after 56 +/- 6 h. Starting at 32 h after
      intoxication, significantly higher values of albumin and total plasma protein
      could be measured in surviving animals (p < 0.05). A significant temporary
      increase in the tumor necrosis factor alpha (TNF-alpha) plasma concentration was
      detected 40-80 h after intoxication in recovering animals (p < 0.05).
      CONCLUSIONS: This porcine model represents a novel tool to analyse multiple
      aspects of liver regeneration following alpha-amanitin poisoning to allow early
      discrimination between a fatal course and survivors. Decreased albumin and total
      plasma protein concentrations in the early intoxication phase indicated a lethal
      outcome, while an increase in the TNF-alpha plasma concentration was identified
      as the earliest prognostic plasma marker detecting liver regeneration a long time
      before liver function was biochemically and clinically impaired.

PMID- 26202415
TI  - Everolimus-based immunosuppression in liver transplant recipients: a single
      centre experience.
AB  - PURPOSE: Everolimus, a mammalian target of rapamycin inhibitor, has been shown to
      reduce growth factor-mediated cell proliferation, but data regarding its
      effectiveness and impact on renal function and recurrence of hepatocellular
      carcinoma (HCC) in liver transplant (LT) recipients are limited. METHODS: We
      evaluated LT recipients with a calcineurin inhibitor (CNI)-based
      immunosuppression regimen in whom everolimus treatment was initiated. The changes
      in laboratory data, including glomerular filtration rate (GFR), compared to the
      baseline (i.e. the day of everolimus conversion), were assessed. RESULTS:
      Totally, 44 consecutive patients (32 men, age 55 +/- 7 years) were commenced on
      everolimus [indications: renal dysfunction post-LT (16 patients, group 1);
      prevention of HCC recurrence (21 patients) or others (7 patients), group 2] at 6
      months (range 1-206) post-LT. After 48 (range 12-76) months, all patients were
      alive without any rejection episodes. Compared to group 2 patients, group 1
      patients had significantly greater improvement in renal function (DGFR: 12 +/- 5
      vs. -0.4 +/- 0.2 ml/min, p = 0.02). GFR at baseline (OR 0.08, p = 0.002) and the
      combination of everolimus + MMF (OR 0.14, p = 0.024) were the factors
      independently associated with improvement in renal function. Finally, HCC
      recurrence was observed less frequently in the everolimus group of patients (n =
      21) compared to the CNI-historical control group (n = 22) with HCC before LT
      [0/21 (0 %) vs. 4/22 (18.5 %), log rank p = 0.055), although the two groups of
      recipients had similar baseline characteristics and follow-up. CONCLUSIONS:
      Everolimus is effective and is associated with low rates of HCC recurrence and
      improvement of renal function in LT recipients.

PMID- 26202416
TI  - Left atrial function is impaired in cirrhosis: a speckle tracking
      echocardiographic study.
AB  - PURPOSE: Abnormalities in left ventricular systolic and diastolic function have
      been described in patients with cirrhosis. There are no studies on left atrial
      (LA) function in these patients. We aimed to evaluate LA function in cirrhosis
      patients using myocardial deformation imaging. METHODS: We included 111
      hospitalized and ambulatory patients with cirrhosis and 18 healthy controls. A
      comprehensive echocardiographic evaluation was performed; LA strain was assessed
      using velocity vector imaging. RESULTS: Peak atrial longitudinal strain at the
      end of ventricular systole was lower in patients [41.9 % (34.4-51.0) vs. 48.0 %
      (42.0-57.1), p = 0.02]. No differences were found in atrial strain before atrial
      contraction in patients and controls [17.5 % (14.3-22.4) vs. 20.7 % (14.1-26.3),
      p = 0.14]. On multivariate linear regression analysis, E' velocity was the only
      variable independently associated with peak atrial longitudinal strain (R (2) =
      47 %). No correlation was found between the LA volume index (LAVI) and peak
      atrial longitudinal strain (r = -0.136, p = 0.219). Peak atrial longitudinal
      strain performed better than LAVI in identifying patients with elevated filling
      pressures (AUC = 0.81 vs. 0.52). CONCLUSIONS: Patients with cirrhosis have
      abnormal atrial reservoir function, which may be related to the same factors
      associated with impaired ventricular relaxation. LA enlargement in cirrhosis may
      not reflect elevated filling pressures and should not be used as an isolated
      marker of diastolic dysfunction. The atrial "pump" function does not seem to be
      affected in cirrhosis patients.

PMID- 26202417
TI  - Glycosylation Analysis of Engineered H3N2 Influenza A Virus Hemagglutinins with
      Sequentially Added Historically Relevant Glycosylation Sites.
AB  - The influenza virus surface glycoprotein hemagglutinin (HA) is the major target
      of host neutralizing antibodies. The oligosaccharides of HA can contribute to
      HA's antigenic characteristics. After a leap to humans from a zoonotic host,
      influenza can gain N-glycosylation sequons over time as part of its fitness
      strategy. This glycosylation expansion has not been studied at the structural
      level. Here we examine HA N-glycosylation of H3N2 virus strains that we have
      engineered to closely mimic glycosylation sites gained between 1968 through 2002
      starting with pandemic A/Hong Kong/1/68 (H3N2: HK68). HAs studied include HK68
      and engineered forms with 1, 2, and 4 added sites. We have used: nano-LC-MS(E)
      for glycopeptide composition, sequence and site occupancy analysis, and MALDI-TOF
      MS permethylation profiling for characterization of released glycans. Our study
      reveals that 1) the majority of N-sequons are occupied at >=90%, 2) the class and
      complexity of the glycans varies by region over the landscape of the proteins, 3)
      Asn 165 and Asn 246, which are associated with interactions between HA and SP-D
      lung collectin, are exclusively high mannose type. Based on this study and
      previous reports we provide structural insight as to how the immune system
      responses may differ depending on HA glycosylation. 

PMID- 26202418
TI  - Long-Term Follow-Up of Gastric Banding 10 Years and Beyond.
AB  - BACKGROUND: This investigation assessed the long-term outcome of patients with
      gastric banding implanted more than 10 years ago. METHODS: A total of 73 patients
      undergoing laparoscopic gastric banding between 1997 and 2003 were identified.
      Patients who had their band removed were converted to a laparoscopic gastric
      bypass procedure. RESULTS: The mean preoperative body mass index (BMI) was 44.4
      (SD 5.3). The mean follow-up was 11.6 (SD 2.1) years. The reasons for reoperation
      were leakage (N = 16, 21.9 %), slipping (N = 15, 20.5 %), and insufficient weight
      loss (N = 9, 12.3 %). The band was left in situ in 33 patients (45.2 %). The 5-
      and 10-year survival rates for the banding were 82.2 % (95 %CI 73.9-91.5 %) and
      53.4 % (95 %CI 43.1-66.2 %). Best results were observed in male patients (10-year
      survival rate 76.5 %, 95 %CI 58.7-99.5 %, HR = 0.44, P = 0.043) and patients
      older than 50 years (10-year survival rate 63.8 %, 95 %CI 51.5-79.2 %, HR = 0.41,
      P = 0.006). Overall, the BMI was 31.0 (SD 6.3) at follow-up, excess weight loss
      was 68.1 % (SD 26.4), and the score for the Moorehead-Ardelt Questionnaire was
      1.6 (SD 1.0). Similar results were obtained for patients with and without banding
      failure. CONCLUSION: The present investigation provides evidence that gastric
      banding remains effective after more than 10 years in less than 50 % of initially
      operated patients. Older (>50 years) and male patients seemed to maintain the
      banding as long-time carriers with good results, and these patients subjectively
      profited from this method. Good results can be achieved if patients are followed
      thoroughly, and alternative surgical options for patients who fail may be offered
      with longstanding success.

PMID- 26202419
TI  - Laparoscopic Roux-en-Y Gastric Bypass: Digressions on Number 6.

PMID- 26202420
TI  - Effect of Sleeve Gastrectomy Plus Side-to-Side Jejunoileal Anastomosis for Type 2
      Diabetes Control in an Obese Rat Model.
AB  - BACKGROUND: Sleeve gastrectomy plus side-to-side jejunoileal anastomosis (JI-SG),
      a relatively new approach to bariatric surgeries, has shown promising results for
      treating obesity and metabolic comorbidities. This study investigated the
      feasibility and safety of JI-SG in weight loss and diabetes remission compared
      with sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). METHODS: Forty
      10-week-old male Zucker diabetic fatty rats were randomly assigned to four
      groups: control, SG, JI-SG, and RYGB. Their body weights, food intake, and levels
      of gut hormones (ghrelin, insulin, and glucagon-like peptide-1 (GLP-1)) and
      lipids were measured. RESULTS: Rats in the SG, JI-SG, and RYGB groups
      demonstrated lower food intake and more weight loss 2 weeks postoperatively
      compared with control rats. Furthermore, rats in the JI-SG group achieved more
      weight loss (mean 242.7 +/- 11.2 g) compared with those in the SG and RYGB groups
      (SG, 401.4 +/- 15.1 g and RYGB, 298 +/- 12 g, both P < 0.01). All surgery groups
      demonstrated a decreased fasting insulin, serum glucose, lipid levels, and
      increased GLP-1 postoperatively. The JI-SG group had lower fasting ghrelin levels
      than the RYGB group (168 +/- 19.8 ng/L vs. 182 +/- 16.7 ng/L, P < 0.01) and
      higher fasting GLP-1 levels than the SG group (1.99 +/- 0.11 pmol/L vs. 1.71 +/-
      0.12 pmol/L, P < 0.01) at 12 weeks postoperatively. Over the experimental period,
      the ghrelin levels slowly increased in all surgical groups but remained lower
      than the preoperative and control levels. CONCLUSIONS: JI-SG induced higher
      ghrelin and GLP-1 levels and improved glycemic control in Zucker diabetic fatty
      rats. Compared with SG and RYGB, JI-SG appeared to be a simple, relatively safe,
      and more effective procedure for treating type 2 diabetes and obesity in this
      animal model.

PMID- 26202422
TI  - Translating neuroscience research to oral medicine: oxytocin and human behavior.

PMID- 26202421
TI  - PKR inhibits the DNA damage response, and is associated with poor survival in AML
      and accelerated leukemia in NHD13 mice.
AB  - Increased expression of the interferon-inducible double-stranded RNA-activated
      protein kinase (PKR) has been reported in acute leukemia and solid tumors, but
      the role of PKR has been unclear. Now, our results indicate that high PKR
      expression in CD34(+) cells of acute myeloid leukemia (AML) patients correlates
      with worse survival and shortened remission duration. Significantly, we find that
      PKR has a novel and previously unrecognized nuclear function to inhibit DNA
      damage response signaling and double-strand break repair. Nuclear PKR antagonizes
      ataxia-telangiectasia mutated (ATM) activation by a mechanism dependent on
      protein phosphatase 2A activity. Thus, inhibition of PKR expression or activity
      promotes ATM activation, gamma-H2AX formation, and phosphorylation of NBS1
      following ionizing irradiation. PKR transgenic but not PKR null mice demonstrate
      a mutator phenotype characterized by radiation-induced and age-associated genomic
      instability that was partially reversed by short-term pharmacologic PKR
      inhibition. Furthermore, the age-associated accumulation of somatic mutations
      that occurs in the Nup98-HOXD13 (NHD13) mouse model of leukemia progression was
      significantly elevated by co-expression of a PKR transgene, whereas knockout of
      PKR expression or pharmacologic inhibition of PKR activity reduced the frequency
      of spontaneous mutations in vivo. Thus, PKR cooperated with the NHD13 transgene
      to accelerate leukemia progression and shorten survival. Taken together, these
      results indicate that increased nuclear PKR has an oncogenic function that
      promotes the accumulation of potentially deleterious mutations. Thus, PKR
      inhibition may be a therapeutically useful strategy to prevent leukemia
      progression or relapse, and improve clinical outcomes. 

PMID- 26202423
TI  - Luminescence and fine structure correlation in ZnO permeated porous silicon
      nanocomposites.
AB  - Nanocomposites formed by porous silicon (PS) and zinc oxide (ZnO) have potential
      for applications in optoelectronic devices. However, understanding the
      distribution of both materials in the nanocomposite, and especially the fine
      structure of the synthesized ZnO crystals, is key for future device fabrication.
      This study focuses on the advanced characterization of a range of PS-ZnO
      nanocomposites by using photon- and ion-based techniques, such as X-ray
      absorption spectroscopy (XAS) and elastic backscattering spectroscopy (EBS),
      respectively. PS substrates formed by the electrochemical etching of p(+)-type Si
      are used as host material for the sol-gel nucleation of ZnO nanoparticles.
      Different properties are induced by annealing in air at temperatures ranging from
      200  degrees C to 800  degrees C. Results show that wurtzite ZnO nanoparticles
      form only at temperatures above 200  degrees C, coexisting with Si quantum dots
      (QDs) inside a PS matrix. Increasing the annealing temperature leads to
      structural and distribution changes that affect the electronic and local
      structure of the samples changing their luminescence. Temperatures around 800 
      degrees C activate the formation of a new zinc silicate phase and transform PS
      into an amorphous silicon oxide (SiOx, x~ 2) matrix with a noticeably reduced
      presence of Si QDs. Thus, these changes affect dramatically the emission from
      these nanocomposites and their potential applications. 

PMID- 26202424
TI  - In Vivo Longitudinal (1)H MRS Study of Transgenic Mouse Models of Prion Disease
      in the Hippocampus and Cerebellum at 14.1 T.
AB  - In vivo (1)H MR spectroscopy allows the non invasive characterization of brain
      metabolites and it has been used for studying brain metabolic changes in a wide
      range of neurodegenerative diseases. The prion diseases form a group of fatal
      neurodegenerative diseases, also described as transmissible spongiform
      encephalopathies. The mechanism by which prions elicit brain damage remains
      unclear and therefore different transgenic mouse models of prion disease were
      created. We performed an in vivo longitudinal (1)H MR spectroscopy study at 14.1
      T with the aim to measure the neurochemical profile of Prnp -/- and PrPDelta32
      121 mice in the hippocampus and cerebellum. Using high-field MR spectroscopy we
      were able to analyze in details the in vivo brain metabolites in Prnp -/- and
      PrPDelta32-121 mice. An increase of myo-inositol, glutamate and lactate
      concentrations with a decrease of N-acetylaspartate concentrations were observed
      providing additional information to the previous measurements. 

PMID- 26202425
TI  - Revisiting Glycogen Content in the Human Brain.
AB  - Glycogen provides an important glucose reservoir in the brain since the
      concentration of glucosyl units stored in glycogen is several fold higher than
      free glucose available in brain tissue. We have previously reported 3-4 umol/g
      brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS)
      in conjunction with [1-(13)C]glucose administration in healthy humans, while
      higher levels were reported in the rodent brain. Due to the slow turnover of bulk
      brain glycogen in humans, complete turnover of the glycogen pool, estimated to
      take 3-5 days, was not observed in these prior studies. In an attempt to reach
      complete turnover and thereby steady state (13)C labeling in glycogen, here we
      administered [1-(13)C]glucose to healthy volunteers for 80 h. To eliminate any
      net glycogen synthesis during this period and thereby achieve an accurate
      estimate of glycogen concentration, volunteers were maintained at euglycemic
      blood glucose levels during [1-(13)C]glucose administration and (13)C-glycogen
      levels in the occipital lobe were measured by (13)C MRS approximately every 12 h.
      Finally, we fitted the data with a biophysical model that was recently developed
      to take into account the tiered structure of the glycogen molecule and
      additionally incorporated blood glucose levels and isotopic enrichments as input
      function in the model. We obtained excellent fits of the model to the (13)C
      glycogen data, and glycogen content in the healthy human brain tissue was found
      to be 7.8 +/- 0.3 umol/g, a value substantially higher than previous estimates of
      glycogen content in the human brain. 

PMID- 26202427
TI  - Conquest of the deep, old and cold: an exceptional limpet radiation in Lake
      Baikal.
AB  - Lake Baikal is the deepest, oldest and most speciose ancient lake in the world.
      The lake is characterized by high levels of molluscan species richness and
      endemicity, including the limpet family Acroloxidae with 25 endemic species.
      Members of this group generally inhabit the littoral zone, but have been recently
      found in the abyssal zone at hydrothermal vents and oil-seeps. Here, we use
      mitochondrial and nuclear data to provide a first molecular phylogeny of the Lake
      Baikal limpet radiation, and to date the beginning of intra-lacustrine
      diversification. Divergence time estimates suggest a considerably younger age for
      the species flock compared with lake age estimates, and the beginning of
      extensive diversification is possibly related to rapid deepening and cooling
      during rifting. Phylogenetic relationships and divergence time estimates do not
      clearly indicate when exactly the abyssal was colonized but suggest a timeframe
      coincident with the formation of the abyssal in the northern basin (Middle to
      Late Pleistocene). 

PMID- 26202428
TI  - Explaining large-scale patterns of vertebrate diversity.
AB  - The major clades of vertebrates differ dramatically in their current species
      richness, from 2 to more than 32,000 species each, but the causes of this
      variation remain poorly understood. For example, a previous study noted that
      vertebrate clades differ in their diversification rates, but did not explain why
      they differ. Using a time-calibrated phylogeny and phylogenetic comparative
      methods, I show that most variation in diversification rates among 12 major
      vertebrate clades has a simple ecological explanation: predominantly terrestrial
      clades (i.e. birds, mammals, and lizards and snakes) have higher net
      diversification rates than predominantly aquatic clades (i.e. amphibians,
      crocodilians, turtles and all fish clades). These differences in diversification
      rates are then strongly related to patterns of species richness. Habitat may be
      more important than other potential explanations for richness patterns in
      vertebrates (such as climate and metabolic rates) and may also help explain
      patterns of species richness in many other groups of organisms.

PMID- 26202426
TI  - AMPK Signalling and Defective Energy Metabolism in Amyotrophic Lateral Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is caused by selective loss of upper and
      lower motor neurons by complex mechanisms that are incompletely understood. Motor
      neurons are large, highly polarised and excitable cells with unusually high
      energetic demands to maintain resting membrane potential and propagate action
      potentials. This leads to higher ATP consumption and mitochondrial metabolism in
      motor neurons relative to other cells. Here, we review increasing evidence that
      defective energy metabolism and homeostasis contributes to selective
      vulnerability and degeneration of motor neurons in ALS. Firstly, we provide a
      brief overview of major energetic pathways in the CNS, including glycolysis,
      oxidative phosphorylation and the AMP-activated protein kinase (AMPK) signalling
      pathway, while highlighting critical metabolic interactions between neurons and
      astrocytes. Next, we review evidence from ALS patients and transgenic mutant SOD1
      mice for weight loss, hypermetabolism, hyperlipidemia and mitochondrial
      dysfunction in disease onset and progression. Genetic and therapeutic modifiers
      of energy metabolism in mutant SOD1 mice will also be summarised. We also present
      evidence that additional ALS-linked proteins, TDP-43 and FUS, lead to energy
      disruption and mitochondrial defects in motor neurons. Lastly, we review emerging
      evidence including our own that dysregulation of the AMPK signalling cascade in
      motor neurons is an early and common event in ALS pathogenesis. We suggest that
      an imbalance in energy metabolism should be considered an important factor in
      both progression and potential treatment of ALS. 

PMID- 26202429
TI  - No one's discussing the elephant in the room: contemplating questions of research
      impact and benefit in Aboriginal and Torres Strait Islander Australian health
      research.
AB  - BACKGROUND: There remains a concern that Indigenous Australians have been over
      researched without corresponding improvements in their health; this trend is
      applicable to most Indigenous populations globally. This debate article has a
      dual purpose: 1) to open a frank conversation about the value of research to
      Indigenous Australian populations; and 2) to stimulate ways of thinking about
      potential resolutions to the lack of progress made in the Indigenous research
      benefit debate. DISCUSSION: Capturing the meaning of research benefit takes the
      form of ethical value-oriented methodological considerations in the decision
      making processes of Indigenous research endeavours. Because research practices
      come from Western knowledge bases, attaining such positions in research means
      reconciling both Indigenous and Western knowledge systems to produce new
      methodologies that guide planning, evaluating and monitoring of research
      practices as necessary. Increasingly, more sophisticated performance measures
      have been implemented to ensure academic impact and benefits are captured.
      Assessing societal and other non-academic impacts and benefits however, has not
      been accorded corresponding attention. Research reform has only focussed on
      research translation in more recent years. The research impact debate must take
      account of the various standards of accountability (to whom), impact priorities
      (for whom), positive and negative impacts, and biases that operate in describing
      impact and measuring benefit. SUMMARY: A perennial question in Indigenous
      research discourse is whether the abundance of research conducted; purportedly to
      improve health, is justified and benefits Indigenous people in ways that are
      meaningful and valued by them. Different research stakeholders have different
      conceptions of the value and nature of research, its conduct, what it should
      achieve and the kinds of benefits expected. We need to work collaboratively and
      listen more closely to the voice of Indigenous Australians to better understand,
      demonstrate and measure health research benefits. The authors conclude that as an
      imperative, a systematic benefit assessment strategy that includes identification
      of research priorities and planning, monitoring and evaluation components needs
      to be developed and implemented across research projects. In Indigenous health
      research, this will often mean adopting a benefit-led approach by changing the
      way research is done and preferencing alternative research methodologies. As a
      point of departure to improving impact and reaching mutually beneficial outcomes
      for researchers and partners in Indigenous health research, we need to routinise
      the assessment of benefit from outset of research as one of the standards toward
      which we work.

PMID- 26202430
TI  - Development of 3D-QSAR Model for Acetylcholinesterase Inhibitors Using a
      Combination of Fingerprint, Molecular Docking, and Structure-Based Pharmacophore
      Approaches.
AB  - Acetylcholinesterase (AChE), a serine hydrolase vital for regulating the
      neurotransmitter acetylcholine in animals, has been used as a target for drugs
      and pesticides. With the increasing availability of AChE crystal structures, with
      or without ligands bound, structure-based approaches have been successfully
      applied to AChE inhibitors (AChEIs). The major limitation of these approaches has
      been the small applicability domain due to the lack of structural diversity in
      the training set. In this study, we developed a 3 dimensional quantitative
      structure-activity relationship (3D-QSAR) for inhibitory activity of 89
      reversible and irreversible AChEIs including drugs and insecticides. A 3D
      fingerprint descriptor encoding protein-ligand interactions was developed using
      molecular docking and structure-based pharmacophore to rationalize the structural
      requirements responsible for the activity of these compounds. The obtained 3D
      QSAR model exhibited high correlation value (R(2) = 0.93) and low mean absolute
      error (MAE = 0.32 log units) for the training set (n = 63). The model was
      predictive across a range of structures as shown by the leave-one-out cross
      validated correlation coefficient (Q(2) = 0.89) and external validation results
      (n = 26, R(2) = 0.89, and MAE = 0.38 log units). The model revealed that the
      compounds with high inhibition potency had proper conformation in the active site
      gorge and interacted with key amino acid residues, in particular Trp84 and Phe330
      at the catalytic anionic site, Trp279 at the peripheral anionic site, and Gly118,
      Gly119, and Ala201 at the oxyanion hole. The resulting universal 3D-QSAR model
      provides insight into the multiple molecular interactions determining AChEI
      potency that may guide future chemical design and regulation of toxic AChEIs. 

PMID- 26202431
TI  - Reduced canine BRCA2 expression levels in mammary gland tumors.
AB  - BACKGROUND: Mammary tumors are the most common tumor type in intact female dogs.
      Recently, the breast cancer 2 early onset (BRCA2) gene was proposed to be
      associated with tumorigenesis in dogs. The expression level of BRCA2 is important
      for its DNA repair function in mammalian cells, and its expression level is
      linked to tumorigenesis in mammary tissue. However, the expression of canine
      BRCA2 in mammary tumors is unclear. RESULTS: BRCA2 mRNA levels were compared
      between seven mammary gland samples and seventeen mammary tumor samples isolated
      from dogs. The expression level of canine BRCA2 in mammary tumor samples was
      lower than levels in mammary gland samples. We attempted to identify why the
      BRCA2 expression level was decreased in mammary tumor samples by promoter
      sequencing analysis; however, we did not find any mutations in the canine BRCA2
      promoter that altered BRCA2 transcription levels. We did detect two types of
      BRCA2 splice variants in 8 mammary tumor samples. One of the variants induced a
      frame-shift mutation that could lead to nonsense-mediated mRNA decay, a
      ubiquitous cellular mechanism that eliminates mRNA containing a premature
      termination codon. CONCLUSIONS: Reduced expression of canine BRCA2 mRNA in
      mammary tumor samples is a possible mechanism to explain mammary tumor
      development in dogs. One possible reason for reduced BRCA2 mRNA levels in these
      tumor samples was nonsense-mediated mRNA decay, not mutations in the BRCA2
      promoter region. While it remains unclear why canine BRCA2 expression levels are
      reduced in mammary tumor samples, this study found that the expression level of
      BRCA2 was associated with canine mammary tumorigenesis.

PMID- 26202433
TI  - Promoting mental health in Asia-Pacific: Systematic review focusing on Thailand
      and China.
AB  - Mental health is essential for functioning, general health, and quality of life
      in low and middle-income countries (LAMICs), as for high-income countries. This
      study aimed first to search in the English language peer-reviewed literature for
      reviews of mental health promotion interventions in the Asia-Pacific region. A
      global rapid review by Barry and colleagues indicated a paucity of publications
      on this topic in the peer-reviewed literature. The second aim of the study
      followed from this observation. Two systematic reviews of English language
      literature were conducted as case studies in two countries with known interest in
      mental health promotion, Thailand and China. The reviews covered publications in
      peer-reviewed journals and the "grey" literature. In Thailand, the review
      demonstrated: strong evidence for an empowerment program for human
      immunodeficiency virus (HIV)-infected mothers; a reduction in HIV-related stigma
      in a community-based program; and a coping program for adolescents. The second
      review concerned suicide prevention interventions in China. It found one relevant
      study, a WHO multi-site study of suicide prevention. We found surprisingly little
      evidence in either country of interventions focused on health equity or modifying
      the social determinants of mental health. We agree with Barry and colleagues that
      there is an urgent need to invest in the policy, practice, and research capacity
      for mental health promotion in LAMICs so that mental health promotion can be
      incorporated into the wider health promotion and global health development
      agenda. This includes the Global Action for Health Equity Network. Evidence-based
      interventions in parenting, schools, workplaces, and among older people can be
      initiated or adapted and evaluated in LAMIC settings. 

PMID- 26202434
TI  - Hepatic Clearance Prediction of Nine Human Immunodeficiency Virus Protease
      Inhibitors in Rat.
AB  - This study aimed to determine the rate-limiting step in the overall hepatic
      clearance of the marketed human immunodeficiency virus (HIV) protease inhibitors
      (PI) in rats by predicting the experimentally determined hepatic in vivo
      clearance of these drugs based on in vitro clearance values for uptake and/or
      metabolism. In vitro uptake and metabolic clearance values were determined in
      suspended rat hepatocytes and rat liver microsomes, respectively. In vivo hepatic
      clearance was determined after intravenous bolus administration in rats.
      Excellent in vitro-in vivo correlation (IVIVC; R(2) = 0.80) was observed when
      metabolic intrinsic Cl values were used, which were determined in vitro at a
      single concentration corresponding to the blood concentration observed in rats in
      vivo at the mean residence time. On the contrary, poor IVIVC was observed when in
      vitro metabolic Cl values based on full Michaelis-Menten profiles were used. In
      addition, the use of uptake Cl values or a combination of both uptake and
      metabolic clearance data led to poor predictions of in vivo clearance. Although
      our findings indicate a key role for metabolism in the hepatic clearance of
      several HIV PI in rats, subsequent simulations revealed that inhibition of
      hepatic uptake can lead to altered hepatic clearance for several of these drugs.

PMID- 26202432
TI  - Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE):
      Proposed DSM-5 Diagnosis.
AB  - Over the past 40 years, a significant body of animal and human research has
      documented the teratogenic effects of prenatal alcohol exposure (PAE).
      Neurobehavioral Disorder associated with PAE is proposed as a new clarifying
      term, intended to encompass the neurodevelopmental and mental health symptoms
      associated with PAE. Defining this disorder is a necessary step to adequately
      characterize these symptoms and allow clinical assessment not possible using
      existing physically-based diagnostic schemes. Without appropriate diagnostic
      guidelines, affected individuals are frequently misdiagnosed and treated
      inappropriately (often to their considerable detriment) by mental health,
      educational, and criminal justice systems. Three core areas of deficits
      identified from the available research, including neurocognitive, self
      regulation, and adaptive functioning impairments, are discussed and information
      regarding associated features and disorders, prevalence, course, familial
      patterns, differential diagnosis, and treatment of the proposed disorder are also
      provided. 

PMID- 26202435
TI  - Mucosal, Cellular, and Humoral Immune Responses Induced by Different Live
      Infectious Bronchitis Virus Vaccination Regimes and Protection Conferred against
      Infectious Bronchitis Virus Q1 Strain.
AB  - The objectives of the present study were to assess the mucosal, cellular, and
      humoral immune responses induced by two different infectious bronchitis virus
      (IBV) vaccination regimes and their efficacy against challenge by a variant IBV
      Q1. One-day-old broiler chicks were vaccinated with live H120 alone (group I) or
      in combination with CR88 (group II). The two groups were again vaccinated with
      CR88 at 14 days of age (doa). One group was kept as the control (group III). A
      significant increase in lachrymal IgA levels was observed at 4 doa and then
      peaked at 14 doa in the vaccinated groups. The IgA levels in group II were
      significantly higher than those in group I from 14 doa. Using
      immunohistochemistry to examine changes in the number of CD4(+) and CD8(+) cells
      in the trachea, it was found that overall patterns of CD8(+) cells were dominant
      compared to those of CD4(+) cells in the two vaccinated groups. CD8(+) cells were
      significantly higher in group II than those in group I at 21 and 28 doa. All
      groups were challenged oculonasally with a virulent Q1 strain at 28 doa, and
      their protection was assessed. The two vaccinated groups gave excellent ciliary
      protection against Q1, although group II's histopathology lesion scores and viral
      RNA loads in the trachea and kidney showed greater levels of protection than
      those in group I. These results suggest that greater protection is achieved from
      the combined vaccination of H120 and CR88 of 1-day-old chicks, followed by CR88
      at 14 doa. 

PMID- 26202437
TI  - The therapeutic potential of antibiotics and probiotics in the treatment of
      pouchitis.
AB  - Pouchitis is the most frequent long-term complication of pouch surgery for
      ulcerative colitis. There is consistent evidence on the implication of bacterial
      flora in the pathogenesis of pouchitis, and there is evidence for a therapeutic
      role of antibiotics and probiotics in therapy of this disease. Antibiotics,
      particularly ciprofloxacin and metronidazole, are the mainstay of treatment for
      acute pouchitis. In chronic refractory pouchitis, after having excluded other
      diagnoses (infections, Crohn's disease of the pouch, ischemia and irritable
      pouch), antibiotic combination therapy is the treatment of choice. The highly
      concentrated probiotic mixture VSL#3 has been shown to be effective in prevention
      of pouchitis onset and in maintaining antibiotic-induced remission.

PMID- 26202436
TI  - Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen
      Rv1733c Protects against Tuberculosis.
AB  - Responsible for 9 million new cases of active disease and nearly 2 million deaths
      each year, tuberculosis (TB) remains a global health threat of overwhelming
      dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails
      to confer lifelong protection and to prevent reactivation of latent infection.
      Although 15 new vaccine candidates are now in clinical trials, an effective
      vaccine against TB remains elusive, and new strategies for vaccination are vital.
      BCG vaccination fails to induce immunity against Mycobacterium tuberculosis
      latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have
      been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved
      to induce efficient antitumor immunity. This study investigated an SLP derived
      from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed
      by "dormant" M. tuberculosis and well recognized by T cells from latently M.
      tuberculosis-infected individuals. In order to assess its in vivo immunogenicity
      and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3
      transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon
      positive/tumor necrosis factor-positive (IFN-gamma(+)/TNF(+)) and IFN-gamma(+)
      CD4(+) T cells and Rv1733c-specific antibodies and led to a significant reduction
      in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was
      observed both in a pre- and in a post-M. tuberculosis challenge setting.
      Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy
      of BCG, demonstrating the potential of M. tuberculosis latency antigens to
      improve BCG efficacy. These data suggest a promising role for M. tuberculosis
      latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a
      prophylactic and in a postinfection setting. 

PMID- 26202438
TI  - High-capacity glycolytic and mitochondrial oxidative metabolisms mediate the
      growth ability of glioblastoma.
AB  - Among the primary brain tumors, glioblastoma multiforme (GBM) has a radical
      proliferation ability that complicates the therapeutic modulation of cancer
      progression. The majority of GBM patients have a low survival rate (<1 year) due
      to radical tumor growth and late cancer diagnosis. Previous reports have shown
      that astrocytes have a specific metabolic organization that includes the
      production of lactate, the storage of glycogen, and use of lactate to support
      neurons which possess higher capacity of metabolism compared to neurons. We
      hypothesized that these characteristics of astrocytes could contribute to
      enhanced proliferation of GBM compared to neuroblastoma (NB). Here, we show that
      U87MG cells (a model of GBM) proliferate more rapidly than SH-SY5Y cells (a model
      of NB). A higher extracellular acidification rate and maximal mitochondrial
      oxygen consumption rate were observed in U87MG cells compared to SH-SY5Y cells.
      The expression levels of lactate dehydrogenase (LDH)-A and LDH-B were higher in
      U87MG cells and primary cultured astrocytes than in SH-SY5Y cells and neurons.
      Furthermore, the mRNA levels of succinate dehydrogenase and peroxisome
      proliferator-activated receptor-gamma were high in U87MG cells, suggesting that
      these cells have high capacity for mitochondrial metabolism and uptake of fatty
      acids related to synthesis of the cell membrane, respectively. Taken together, we
      demonstrate that GBM cells are characterized by activation of the LDH-expression
      related glycolytic pathway and mitochondrial metabolic capacity, suggesting two
      innate properties of astrocytes that could provide a driving force for the growth
      ability of GBM. Based on these findings, we propose that therapeutic approaches
      aimed at treating GBM could target LDH for modulating the metabolic properties of
      GBM cells. 

PMID- 26202439
TI  - Effects of school meals based on the New Nordic Diet on intake of signature
      foods: a randomised controlled trial. The OPUS School Meal Study.
AB  - A New Nordic Diet (NND) was developed in the context of the Danish OPUS Study
      (Optimal well-being, development and health for Danish children through a healthy
      New Nordic Diet). Health, gastronomic potential, sustainability and Nordic
      identity were crucial principles of the NND. The aim of the present study was to
      investigate the effects of serving NND school meals compared with the usual
      packed lunches on the dietary intake of NND signature foods. For two 3-month
      periods, 834 Danish children aged 8-11 years received NND school meals or their
      usual packed lunches brought from home (control) in random order. The entire diet
      was recorded over 7 consecutive days using a validated Web-based Dietary
      Assessment Software for Children. The NND resulted in higher intakes during the
      entire week (% increase) of root vegetables (116 (95 % CI 1.93, 2.42)), cabbage
      (26 (95 % CI 1.08, 1.47)), legumes (22 (95 % CI 1.06, 1.40)), herbs (175 (95 % CI
      2.36, 3.20)), fresh berries (48 (95 % CI 1.13, 1.94)), nuts and seeds (18 (95 %
      CI 1.02, 1.38)), lean fish and fish products (47 (95 % CI 1.31, 1.66)), fat fish
      and fish products (18 (95 % CI 1.02, 1.37)) and potatoes (129 (95 % CI 2.05,
      2.56)). Furthermore, there was a decrease in the number of children with zero
      intakes when their habitual packed lunches were replaced by NND school meals. In
      conclusion, this study showed that the children increased their intake of NND
      signature foods, and, furthermore, there was a decrease in the number of children
      with zero intakes of NND signature foods when their habitual packed lunches were
      replaced by school meals following the NND principles. 

PMID- 26202440
TI  - Bimatoprost 0.01 % for previously treated patients with open-angle glaucoma or
      ocular hypertension in the Korean clinical setting.
AB  - PURPOSE: To evaluate the occurrence of hyperemia with, and efficacy of,
      bimatoprost 0.01 % for patients in Korea previously treated for open-angle
      glaucoma (OAG; including normal tension glaucoma) or ocular hypertension (OHT).
      METHODS: In this multicenter, observational study (Asia Pacific Patterns from
      Early Access of Lumigan 0.01 % in Korea; APPEAL Korea), patients with unachieved
      target intraocular pressure (IOP) despite previous treatment received bimatoprost
      0.01 % daily for 12 weeks. The primary endpoint was incidence of hyperemia and
      its severity, graded using the standard 5-point photographic scale and grouped as
      "none to mild" and "moderate to severe". Hyperemia shifts were reported. IOP and
      adverse events (AEs) were recorded. RESULTS: Of 800 patients (intent-to
      treat/safety population), 248 were switched from previous treatment to
      bimatoprost 0.01 % monotherapy. Hyperemia shifts from baseline at weeks 6 and 12
      were unchanged (84.8, 89.8 %), improved (4.4, 4.8 %), or worsened (10.8, 5.4 %),
      respectively. The shift was significant at week 6 (P < 0.0001). Hyperemia did not
      worsen significantly in patients previously receiving a prostaglandin analog or
      prostamide (PGA/PSD). Baseline mean IOP +/- SD was 17.0 +/- 5.7 mmHg, decreasing
      to 14.6 +/- 3.8 mmHg (P < 0.0001) after 6 weeks, and to 14.7 +/- 3.6 mmHg (P <
      0.0001) after 12 weeks. Patients switched from PGA or PSD (excluding bimatoprost
      0.03 %) to bimatoprost 0.01 % experienced significant IOP reductions from
      baseline. Treatment-related ocular AEs were reported by 37 patients, the most
      common being hyperemia (7.3 %). CONCLUSIONS: This subanalysis of the APPEAL Korea
      study supports use of bimatoprost 0.01 % for previously treated patients with OAG
      (including normal tension glaucoma) or OHT who did not reach target IOP or were
      intolerant of previous treatment.

PMID- 26202441
TI  - Unilateral medial rectus resection for the treatment of recurrent exotropia in
      children.
AB  - PURPOSE: To investigate the outcomes of unilateral medial rectus resection (UMR
      res) for the treatment of small to moderate angles of recurrent exotropia in
      children followed up for a minimum of 6 months. METHODS: This study is a
      retrospective, consecutive, interventional case series in which 48 children who
      underwent UMR-res (range 4.0-7.5 mm) for recurrent exotropia [range 12-25 prism
      diopters (PD)] between January 2009 and February 2013 were enrolled. Of these 48
      children, 32 had recurrent intermittent exotropia, and 16 had recurrent constant
      exotropia. A successful surgical alignment was defined as +5 to -10 PD of
      orthophoria in the primary position while viewing distant or near targets.
      RESULTS: At a mean follow-up of 12 months, the surgical success rate was 75 %
      (36/48), and the undercorrection rate was 25 % (12/48). No patient exhibited
      overcorrection. The success rates of the UMR-res in the recurrent intermittent
      exotropia group and recurrent constant exotropia group were 78 % and 69 %,
      respectively, and were not significantly different (P = 0.50). In the initial
      surgical procedure groups, the success rates of patients with bilateral lateral
      rectus recession, unilateral lateral rectus recession, and unilateral lateral
      rectus recession combined with medial rectus resection were 81.8 % (18/22), 81.25
      % (13/16), and 50 % (5/10), respectively. The surgical success rates did not
      differ among these three groups (P = 0.122). CONCLUSION: Based on our results,
      UMR-res would appear to be an effective and safe procedure for the treatment of
      intermittent or constant recurrent exotropia of <=25 PD in children.

PMID- 26202443
TI  - Individual variations in treatment decisions by Swedish rheumatologists regarding
      biological drugs for rheumatoid arthritis.
AB  - OBJECTIVES: In Sweden, reports indicate surprisingly large regional variation in
      prescription of biological drugs despite a growing number of clinical studies
      describing their beneficial effects and guidelines by professional organizations
      and agencies. Our objectives were to ascertain whether there is also variation
      between individual rheumatologists in prescribing biologics to patients with
      rheumatoid arthritis (RA) and to evaluate reasons for treatment choices. METHOD:
      Ten hypothetical patient cases were constructed and presented to 26
      rheumatologists in five regions in Sweden. The cases were based on actual cases
      and were thoroughly elaborated by a senior rheumatologist and pre-tested in a
      pilot study. The respondents were asked whether they would treat the patients
      with a biological agent (Yes/No) and to explain their decisions. RESULTS: The
      response rate was 26/105 (25%). Treatment choices varied considerably between the
      rheumatologists, some prescribing biologics to 9/10 patients and others to 2/10.
      In five of the 10 hypothetical cases, approximately half of the respondents would
      prescribe biologics. No regions with particularly high or low prescription were
      identified. Both the decisions to prescribe biologics and also not to prescribe
      biologics were mainly motivated by medical reasons. Some rheumatologists also
      referred to lifestyle-related factors or the social function of the patient.
      CONCLUSIONS: The choice of initiation of biologics varied substantially among
      rheumatologists presented with hypothetical patient cases, and there were also
      disparities between rheumatologists practicing at the same clinic. Treatment
      choices were motivated primarily by medical reasons. This situation raises
      concerns about a lack of consensus in RA treatment strategies.

PMID- 26202442
TI  - Comparison of microinsicion vitrectomy and conventional 20-gauge vitrectomy for
      severe proliferative diabetic retinopathy.
AB  - PURPOSE: To compare the outcomes of 23-gauge (G) and 25G vitrectomy to 20G
      vitrectomy on eyes with severe proliferative diabetic retinopathy (PDR). METHODS:
      The medical records of 424 eyes of 347 patients with severe PDR were reviewed.
      There were 80 eyes that had 23G, 174 eyes that had 25G, and 170 eyes that had 20G
      vitrectomy. The incidences of postoperative vitreous hemorrhage, intraoperative
      retinal breaks, retinal detachment, and neovascular glaucoma were compared.
      RESULTS: The incidence of intraoperative retinal breaks was significantly lower
      in the 23G group (21 %) than in the 20G group (35 %, P = 0.03) but not in the 25G
      group (26 %, P = 0.057). The incidence of postoperative retinal detachment was
      not significantly different among the three groups (P = 0.73). The incidence of
      postoperative vitreous hemorrhage that developed >=1 month after vitrectomy was
      not different whether the eyes had panretinal photocoagulation or not (P = 0.15).
      The incidence of postoperative neovascular glaucoma was significantly lower in
      the 25G group (3 %) than in the 20G group (11 %, P = 0.01) but not significant
      compared with that in the 23G group (8 %, P = 0.72). CONCLUSION: The lower
      incidence of intraoperative retinal breaks and postoperative neovascular glaucoma
      after microincision vitrectomy indicates that microincision vitrectomy should be
      considered for eyes with severe PDR.

PMID- 26202444
TI  - Phlorotannins suppress adipogenesis in pre-adipocytes while enhancing
      osteoblastogenesis in pre-osteoblasts.
AB  - Osteoporosis, a prevalent bone disease in an aging population, is considered to
      be closely related to osteoblastogenesis and adipogenesis. As a part of an
      ongoing trend to develop natural substances that attenuate osteoporotic
      conditions, edible brown algae E. cava and its bioactive constituents were tested
      for their effects on adipogenic differentiation in 3T3-L1 fibroblasts and
      osteoblast differentiation in MC3T3-E1 pre-osteoblasts. Following an activity
      based isolation, three phlorotannin derivatives, triphlorethol-A (1), eckol (2)
      and dieckol (3), were isolated. Anti-adipogenesis effect of phlorotannins at the
      concentration of 20 uM was observed by reduced lipid accumulation and the
      suppressed expression of adipogenic differentiation markers. In addition,
      isolated phlorotannins successfully enhanced the osteoblast differentiation as
      indicated by increased alkaline phosphatase activity along with raised levels of
      osteoblastogenesis indicators and intracellular calcification at the
      concentration of 20 uM. In conclusion, E. cava is suggested as a source for
      functional food ingredients, especially phlorotannin derivatives that can be
      utilized for extenuating osteoporosis and obesity.

PMID- 26202446
TI  - Breakfast is associated with the metabolic syndrome and school performance among
      Taiwanese children.
AB  - Skipping breakfast is associated with adverse child health profiles including
      obesity, higher blood pressure, higher serum cholesterol, and poor cognitive
      function. We aimed to explore the association between breakfast with school
      performance and the metabolic syndrome (MetS) in Taiwanese children. Participants
      were enrolled from the representative Elementary School Children's Nutrition and
      Health Survey in Taiwan (2001-2002). Diet, waist circumference, blood pressure,
      blood glucose, triglyceride, and high-density lipoprotein cholesterol
      concentrations were assessed in 1287 boys and 1114 girls. Their school and social
      performances were examined using the modified Scale for Assessing Emotional
      Disturbance questionnaire. Logistic and linear regression analyses were used to
      estimate the risk of MetS and also the association between breakfast consumption
      frequency and school or social performance. When breakfast consumption was
      regular, overall dietary quality was better. Children who consumed breakfast
      daily exhibited lower risks of high blood pressure (OR=0.37, 95% CI=0.19-0.71)
      and of MetS (OR=0.22, 95% CI=0.09-0.51) compared with children who consumed
      breakfast 0-4 times per week. Furthermore, children who consumed breakfast daily
      exhibited a higher overall competence (OC) score (beta=0.71, p<0.05) in a dose
      response manner (p for trend=0.02). This association was not dependent on overall
      diet or MetS. In conclusion, consuming breakfast daily is associated with better
      school performance, a lower risk of high blood pressure, and MetS independent of
      overall dietary quality. Thus, breakfast on school days is a factor in school
      performance and health.

PMID- 26202445
TI  - Accumulation of transcription factors and cell signaling-related proteins in the
      nucleus during citrus-Xanthomonas interaction.
AB  - The nucleus is the maestro of the cell and is involved in the modulation of cell
      signaling during stress. We performed a comprehensive nuclear proteome analysis
      of Citrus sinensis during interaction with host (Xanthomonas citri pv. citri-Xcc)
      and non-host (Xanthomonas oryzae pv. oryzae-Xoo) pathogens. The nuclear proteome
      was obtained using a sequential method of organelle enrichment and determined by
      nano-LC-MS/MS analysis. A total of 243 proteins accumulated differentially during
      citrus-Xanthomonas interaction, belonging to 11 functional groups, with signaling
      and transcription-related proteins dominating. MADS-box transcription factors,
      DEAD-box RNA helicase and leucine aminopeptidase, mainly involved in jasmonic
      acid (JA) responses, were in high abundance during non-host interaction (Xoo).
      Signaling-related proteins like serine/threonine kinase, histones (H3.2, H2A),
      phosphoglycerate kinase, dynamin, actin and aldolase showed increased
      accumulation early during Xoo interaction. Our results suggest that there is a
      possible involvement of JA-triggered defense responses during non-host
      resistance, with early recognition of the non-host pathogen. 

PMID- 26202447
TI  - Hypoxia promotes vasculogenic mimicry formation by the Twist1-Bmi1 connection in
      hepatocellular carcinoma.
AB  - Aggressive tumor cells can mimic embryonic vasculogenic networks and form
      vasculogenic mimicry (VM). Preliminary studies demonstrated that hypoxia can
      promote VM formation; however, the underlying mechanism remains unclear. The
      present study aimed to investigate the role of the Twist1-Bmi1 connection in
      hypoxia-induced VM formation and the underlying mechanism. In the in vitro
      experiments, western blot analysis demonstrated that hypoxia upregulated the
      expression of Twist1, Bmi1, epithelial-mesenchymal transition (EMT) markers, stem
      cell markers and VM-associated markers. The 3D culture assay showed that hypoxia
      promoted VM formation in hepatocellular carcinoma (HCC) cell lines. Using
      transfection and in vitro cell experiments, the Twist1-Bmi1 connection was
      confirmed to have an important role in inducing EMT, cell stemness and VM
      formation. In the in vivo experiments, the murine hypoxia models were established
      via incomplete femoral artery ligation and the mechanism by which hypoxia
      promoted Twist1 and Bmi1 expression and led to VM formation was demonstrated by
      immunohistochemistry staining and endomucin/periodic acid Schiff double-staining.
      In conclusion, hypoxia upregulate the expression of Twist1 and Bmi1, and these
      two proteins have an important role in inducing EMT and cancer cell stemness,
      which contributed to VM formation.

PMID- 26202448
TI  - Overview of the gene regulation network and the bacteria biotope tasks in
      BioNLP'13 shared task.
AB  - BACKGROUND: We present the two Bacteria Track tasks of BioNLP 2013 Shared Task
      (ST): Gene Regulation Network (GRN) and Bacteria Biotope (BB). These tasks were
      previously introduced in the 2011 BioNLP-ST Bacteria Track as Bacteria Gene
      Interaction (BI) and Bacteria Biotope (BB). The Bacteria Track was motivated by a
      need to develop specific BioNLP tools for fine-grained event extraction in
      bacteria biology. The 2013 tasks expand on the 2011 version by better addressing
      the biological knowledge modeling needs. New evaluation metrics were designed for
      the new goals. Moving beyond a list of gene interactions, the goal of the GRN
      task is to build a gene regulation network from the extracted gene interactions.
      BB'13 is dedicated to the extraction of bacteria biotopes, i.e. bacterial
      environmental information, as was BB'11. BB'13 extends the typology of BB'11 to a
      large diversity of biotopes, as defined by the OntoBiotope ontology. The
      detection of entities and events is tackled by distinct subtasks in order to
      measure the progress achieved by the participant systems since 2011. RESULTS:
      This paper details the corpus preparations and the evaluation metrics, as well as
      summarizing and discussing the participant results. Five groups participated in
      each of the two tasks. The high diversity of the participant methods reflects the
      dynamism of the BioNLP research community. CONCLUSION: The evaluation results
      suggest new research directions for the improvement and development of
      Information Extraction for molecular and environmental biology. The Bacteria
      Track tasks remain publicly open; the BioNLP-ST website provides an online
      evaluation service, the reference corpora and the evaluation tools.

PMID- 26202450
TI  - Atlantoaxial Rotatory Subluxation after Removal of a Ventriculoperitoneal Shunt
      in the Supine-Lateral Position.
AB  - Atlantoaxial rotatory subluxation (AARS) is an uncommon disease with a greater
      prevalence in children than adults. So far there has only been one report of AARS
      after surgery related to ventriculoperitoneal (VP) shunting. We present a new
      case of AARS closed reduction treatment after VP shunt removal in an 8-year-old
      girl with wound pain on the back of her head and torticollis after surgery. Her
      head was rotated in the spine-lateral position during surgery. The diagnosis of
      AARS was established by 3D-computed tomography. The rotatory subluxation was
      cured after cervical traction therapy. The successful closed reduction was the
      consequence of early detection and conservative treatment, which are important
      constituents in the management of AARS.

PMID- 26202449
TI  - Real-time measurement of hyperpolarized lactate production and efflux as a
      biomarker of tumor aggressiveness in an MR compatible 3D cell culture bioreactor.
AB  - We have developed a 3D cell/tissue culture bioreactor compatible with
      hyperpolarized (HP) (13)C MR and interrogated HP [1-(13)C]lactate production and
      efflux in human renal cell carcinoma (RCC) cells. This platform is capable of
      resolving intracellular and extracellular HP lactate pools, allowing the kinetic
      measurement of lactate production and efflux in the context of cancer
      aggressiveness and response to therapy. HP (13)C MR studies were performed on
      three immortalized human renal cell lines: HK2, a normal renal proximal tubule
      cell line from which a majority of RCCs arise, UMRC6, a cell line derived from a
      localized RCC, and UOK262, an aggressive and metastatic RCC. The intra- (Lacin )
      and extracellular (Lacex ) HP lactate signals were robustly resolved in dynamic
      (13)C spectra of the cell lines due to a very small but reproducible chemical
      shift difference (0.031 +/- 0.0005 ppm). Following HP [1-(13)C]pyruvate delivery,
      the ratio of HP Lacin /Lacex was significantly lower for UOK262 cells compared
      with both UMRC6 and HK2 cells due to a significant (p < 0.05) increase in the
      Lacex pool size. Lacin /Lacex correlated with the MCT4 mRNA expression of the
      cell lines, and inhibition of MCT4 transport using DIDS resulted in a significant
      reduction in the HP Lacex pool size. The extension of these studies to living
      patient-derived RCC tissue slices using HP [1,2-(13)C2]pyruvate demonstrated a
      similarly split lactate doublet with a high Lacex pool fraction; in contrast,
      only a single NMR resonance is noted for HP [5-(13)C]glutamate, consistent with
      intracellular localization. These studies support the importance of lactate
      efflux as a biomarker of cancer aggressiveness and metastatic potential, and the
      utility of the MR compatible 3D cell/tissue culture bioreactor to study not only
      cellular metabolism but also transport. Additionally, this platform offers a
      sophisticated way to follow therapeutic interventions and screen novel therapies
      that target lactate export.

PMID- 26202451
TI  - The Irish Kidney Gene Project--Prevalence of Family History in Patients with
      Kidney Disease in Ireland.
AB  - BACKGROUND: The prevalence of kidney disease (KD) due to inherited genetic
      conditions in Ireland is unknown. The aim of this study was to characterise an
      adult kidney disease population in Ireland and to identify familial clusters of
      kidney disease within the population. METHODS: This was a multicenter cross
      sectional study of patients with kidney disease in the Republic of Ireland, from
      January 2014 to September 2014, recruiting from dialysis units and out-patient
      renal departments. A survey was performed by collecting data on etiology of
      kidney disease and whether a family history of kidney disease exists. Medical
      records were cross-referenced to confirm the etiology of kidney disease. RESULTS:
      A total of 1,840 patients were recruited with a mean age of 55.9 years (range 17
      94.5) and a male predominance (n = 1,095; 59.5%). A positive family history was
      reported by 629 participants (34.2%). Excluding polycystic kidney disease (n =
      134, 7.3%), a positive family history was reported by 495 participants (26.9%).
      Kidney disease due to an unknown etiology was the commonest etiology in the non
      polycystic kidney disease group with a positive family history (10.6%, n = 67).
      Kidney diseases that are not classically associated with familial inheritance
      including tubulo-interstitial kidney disease, congenital abnormalities of the
      kidney and urinary tract and glomerulonephritis demonstrated familial clustering.
      CONCLUSION: In an Irish non-polycystic kidney disease population, 26.9% reports a
      positive family history. The commonest etiology of kidney disease in the positive
      family history cohort, excluding autosomal dominant polycystic kidney disease,
      was kidney disease due to unknown etiology. Examining families with kidney
      disease provides an opportunity to better understand disease pathogenesis and
      potentially identify genetic predispositions to kidney disease.

PMID- 26202454
TI  - On the validity of empirical potentials for simulating radiation damage in
      graphite: a benchmark.
AB  - In this work, the ability of methods based on empirical potentials to simulate
      the effects of radiation damage in graphite is examined by comparing results for
      point defects, found using ab initio calculations based on density functional
      theory (DFT), with those given by two state of the art potentials: the
      Environment-Dependent Interatomic Potential (EDIP) and the Adaptive
      Intermolecular Reactive Empirical Bond Order potential (AIREBO). Formation
      energies for the interstitial, the vacancy and the Stone-Wales (5775) defect are
      all reasonably close to DFT values. Both EDIP and AIREBO can thus be suitable for
      the prompt defects in a cascade, for example. Both potentials suffer from
      arefacts. One is the pinch defect, where two alpha-atoms adopt a fourfold
      coordinated sp(3) configuration, that forms a cross-link between neighbouring
      graphene sheets. Another, for AIREBO only, is that its ground state vacancy
      structure is close to the transition state found by DFT for migration. The EDIP
      fails to reproduce the ground state self-interstitial structure given by DFT, but
      has nearly the same formation energy. Also, for both potentials, the energy
      barriers that control diffusion and the evolution of a damage cascade, are not
      well reproduced. In particular the EDIP gives a barrier to removal of the Stone
      Wales defect as 0.9 eV against DFT's 4.5 eV. The suite of defect structures used
      is provided as supplementary information as a benchmark set for future
      potentials.

PMID- 26202453
TI  - Lipoprotein(a) predicts a new onset of chronic kidney disease in people with Type
      2 diabetes mellitus.
AB  - AIMS: We investigated the association between lipoprotein(a) [Lp(a)] level and
      new-onset chronic kidney disease (CKD) in patients with Type 2 diabetes. METHODS:
      We conducted a prospective cohort study from March 2003 to December 2004 with a
      median follow-up time of 10.1 years. Patients aged 25-75 years with Type 2
      diabetes and without CKD [estimated glomerular filtration rate (eGFR) >= 90
      ml/min/1.73 m(2) ) were consecutively enrolled. The eGFR was measured at least
      twice every year , and new-onset CKD was defined as a decreased eGFR status of <
      60 ml/min/1.73 m(2) using a Chronic Kidney Disease Epidemiology Collaboration
      (CKD-EPI) equation. RESULTS: Of the 862 patients who were enrolled, 560 (65.0%)
      completed the follow-up and 125 (22.3%) progressed to CKD. The mean age and
      duration of diabetes were 53.3 +/- 9.6 and 7.5 +/- 6.0 years, respectively. The
      baseline eGFR was 101.8 +/- 11.3 ml/min/1.73 m(2) . After adjusting for multiple
      confounding factors, a Cox hazard regression analysis revealed that the third
      tertile of Lp(a) was significantly associated with the development of CKD during
      the observation period when compared with the first tertile [hazard ratio 2.12
      (95% confidence interval 1.33-3.36); P = 0.001). CONCLUSIONS: In this
      prospective, longitudinal, observational cohort study, we demonstrated that the
      Lp(a) level was an independent prognostic factor for the future development of
      CKD in patients with Type 2 diabetes.

PMID- 26202452
TI  - Effects of aerobic and resistance training on abdominal fat, apolipoproteins and
      high-sensitivity C-reactive protein in adolescents with obesity: the HEARTY
      randomized clinical trial.
AB  - OBJECTIVES: To investigate the effects of aerobic training, resistance training,
      or both on abdominal subcutaneous fat (subcutaneous adipose tissue (SAT)) (deep
      and superficial), visceral fat (visceral adipose tissue (VAT)), apolipoproteins A
      1 and B (ApoA-1, ApoB), ApoB/ApoA-1 ratio and high-sensitivity C-reactive protein
      (HSCRP) in post-pubertal adolescents with obesity. PARTICIPANTS: After a 4-week
      supervised moderate-intensity exercise run-in period, 304 postpubertal
      adolescents with overweight (body mass index (BMI) ?85th percentile for age and
      sex+diabetes risk factor) or obesity (?95th BMI percentile) aged 14-18 years were
      randomized to four groups for 22 weeks (5 months): aerobic training, resistance
      training, combined training or a non-exercising control. METHODS: This study used
      a randomized controlled design. All groups received dietary counseling designed
      to promote healthy eating with a maximum daily energy deficit of 250 kcal.
      Abdominal fat (SAT and VAT) at the level of the fourth and fifth lumbar vertebrae
      (L4-L5) was measured by magnetic resonance imaging and ApoA-1, ApoB and HSCRP
      were measured after a 12-h fast at baseline and after 6 months. RESULTS: Changes
      in SAT at L4-L5 were -16.2 cm(2) in aerobic (P=0.04 vs control), -22.7 cm(2) in
      resistance (P=0.009 vs control) and -18.7 cm(2) in combined (P=0.02 vs control).
      Combined training reduced ApoB levels from 0.81+/-0.02 to 0.78+/-0.02 g l(-1)
      (P=0.04 vs control) and ApoB/ApoA-1 ratio from 0.67+/-0.02 to 0.64+/-0.02 (P=0.02
      vs control and P=0.04 vs aerobic). There were no significant differences in VAT,
      ApoA-1 or HSCRP levels between groups. CONCLUSIONS: Aerobic and resistance
      training and their combination decreased abdominal SAT in adolescents with
      obesity. Combined training caused greater improvements in ApoB/ApoA-1 ratio
      compared with aerobic training alone.

PMID- 26202455
TI  - Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1
      signaling under oxLDL stimulation.
AB  - SCOPE: Atherosclerosis is believed to be an independent predictor of
      cardiovascular diseases. A growing body of evidence suggests that quercetin is a
      potent antioxidant and anti-inflammatory compound. The molecular mechanisms
      underlying its protective effects against oxidative stress in human endothelial
      cells remain unclear. This study was designed to confirm the hypothesis that
      quercetin inhibits oxidized LDL (oxLDL) induced endothelial oxidative damage by
      activating sirtuin 1 (SIRT1) and to explore the role of adenosine monophosphate
      activated protein kinase (AMPK), which is a negative regulator of Nicotinamide
      adenine dinucleotide phosphate-oxidase (NADPH oxidase) and free radicals. METHODS
      AND RESULTS: Human umbilical vein endothelial cells were treated with oxLDL with
      or without quercetin pretreatment. We found that quercetin pretreatment increased
      SIRT1 mRNA expression. In fact, quercetin protected against oxLDL-impaired SIRT1
      and AMPK activities and reduced oxLDL-activated NOX2 and NOX4. However, silencing
      SIRT1 and AMPK diminished the protective function of quercetin against oxidative
      injuries. The results also indicated that oxLDL suppressed AKT/endothelial NO
      synthase, impaired mitochondrial dysfunction, and enhanced reactive oxygen
      species formation, activating the Nuclear Factor Kappa B (NF-kappaB) pathway.
      CONCLUSION: These results provide new insight regarding the possible molecular
      mechanisms of quercetin. Quercetin suppresses oxLDL-induced endothelial oxidative
      injuries by activating SIRT1 and modulating the AMPK/NADPH
      oxidase/AKT/endothelial NO synthase signaling pathway.

PMID- 26202456
TI  - Insights on Clusters Formation Mechanism by Time of Flight Mass Spectrometry. 1.
      The Case of Ethanol-Water Clusters.
AB  - In the present work, water clusters with the addition of an electrophilic
      molecule such as ethanol have been studied by time of flight mass spectrometry
      (TOFMS). Mass distributions of molecular clusters of ethanol, water, and ethanol
      water mixed clusters were obtained by two different ionization methods: electron
      ionization (EI) and picosecond laser photo-ionization (PI) at a wavelength of 355
      nm. It was shown that short pulse laser ionization increases the signal intensity
      and promotes the extension of the detected mass range of the clusters in
      comparison with EI. Much larger clusters were detected in our experiments with
      respect to the current literature. The autocorrelation function (AF) was
      introduced in the analysis of the composition of the water clusters in terms of
      fundamental periodicities for obtaining information on clusters formation
      mechanisms. Besides, it was found that ethanol molecules are capable of
      substitutional interaction with hydrogen-bonded water clusters in ethanol-water
      binary mixtures but the self-association of ethanol was the dominant process.
      Moreover, the increase of ethanol concentration promotes both the formation of
      hydrated ethanol clusters and the self-association of ethanol clusters in ethanol
      water binary mixtures. The formation of water-rich clusters and subsequent
      metastable fragmentation were found to be the dominant processes determining the
      water-rich cluster distribution, irrespective of the ionization process, while
      the ionization process significantly affects the ethanol-rich cluster
      distribution.

PMID- 26202457
TI  - Inkjet-printed gold nanoparticle surfaces for the detection of low molecular
      weight biomolecules by laser desorption/ionization mass spectrometry.
AB  - Effective detection of low molecular weight compounds in matrix-assisted laser
      desorption/ionization (MALDI) mass spectrometry (MS) is often hindered by matrix
      interferences in the low m/z region of the mass spectrum. Here, we show that
      monolayer-protected gold nanoparticles (AuNPs) can serve as alternate matrices
      for the very sensitive detection of low molecular weight compounds such as amino
      acids. Amino acids can be detected at low fmol levels with minimal interferences
      by properly choosing the AuNP deposition method, density, size, and monolayer
      surface chemistry. By inkjet-printing AuNPs at various densities, we find that
      AuNP clusters are essential for obtaining the greatest sensitivity. Graphical
      Abstract ?. 

PMID- 26202458
TI  - Robust gene expression and mutation analyses of RNA-sequencing of formalin-fixed
      diagnostic tumor samples.
AB  - Current genomic studies are limited by the availability of fresh tissue samples.
      Here, we show that Illumina RNA sequencing of formalin-fixed diagnostic tumor
      samples produces gene expression that is strongly correlated with matched frozen
      tumor samples (r > 0.89). In addition, sequence variations identified from FFPE
      RNA show 99.67% concordance with that from exome sequencing of matched frozen
      tumor samples. Because FFPE is a routine diagnostic sample preparation, the
      feasibility results reported here will facilitate the setup of large-scale
      research and clinical studies in medical genomics that are currently limited by
      the availability of fresh frozen samples. 

PMID- 26202459
TI  - Inhibition of Kv7/M Channel Currents by the Local Anesthetic Chloroprocaine.
AB  - BACKGROUND: Chloroprocaine is a local ester anesthetic, producing excellent
      sensory block in clinical use. The Kv7/M potassium channel plays an important
      role in the control of neuronal excitability. In this study, we investigated the
      effects of the local anesthetic chloroprocaine on Kv7/M channels as well as the
      effect of retigabine on chloroprocaine-induced seizures. METHODS: A perforated
      whole-cell patch technique was used to record Kv7 currents from HEK293 cells and
      M-type currents from rat dorsal root ganglion (DRG) neurons. RESULTS:
      Chloroprocaine produced a number of effects on Kv7.2/Kv7.3 currents, including a
      lowering of current amplitudes, a rightward shift in the voltage-dependent
      activation curves, and a slowing of channel activation. Chloroprocaine had a more
      selective inhibitory effect on the homomeric Kv7.3 and heteromeric Kv7.2/Kv7.3
      channels than on the homomeric Kv7.2 channel. Chloroprocaine also inhibited
      native M channel currents and induced a depolarization of the DRG neuron membrane
      potential. CONCLUSION: Taken together, the findings indicate that chloroprocaine
      concentration dependently inhibited Kv7/M channel currents.

PMID- 26202460
TI  - HEX goes Open Access.

PMID- 26202461
TI  - Process analysis of trauma-focused cognitive behavioural therapy for individuals
      with schizophrenia.
AB  - OBJECTIVE: Therapeutic alliance, modality, and ability to engage with the process
      of therapy have been the main focus of research into what makes psychotherapy
      successful. Individuals with complex trauma histories or schizophrenia are
      suggested to be more difficult to engage and may be less likely to benefit from
      therapy. This study aimed to track the in-session 'process' of working alliance
      and emotional processing of trauma memories for individuals with schizophrenia.
      DESIGN: The study utilized session recordings from the treatment arm of an open
      randomized clinical trial investigating trauma-focused cognitive behavioural
      therapy (TF-CBT) for individuals with schizophrenia (N = 26). METHOD: Observer
      measures of working alliance, emotional processing, and affect arousal were rated
      at early and late phases of therapy. Correlation analysis was undertaken for
      process measures. Temporal analysis of expressed emotions was also reported.
      RESULTS: Working alliance was established and maintained throughout the therapy;
      however, agreement on goals reduced at the late phase. The participants appeared
      to be able to engage in emotional processing, but not to the required level for
      successful cognitive restructuring. CONCLUSION: This study undertook novel
      exploration of process variables not usually explored in CBT. It is also the
      first study of process for TF-CBT with individuals with schizophrenia. This
      complex clinical sample showed no difficulty in engagement; however, they may not
      be able to fully undertake the cognitive-emotional demands of this type of
      therapy. Clinical and research implications and potential limitations of these
      methods are considered. PRACTITIONER POINTS: This sample showed no difficulties
      engaging with TF-CBT and forming a working alliance. However, the participants
      may not have achieved a level of active involvement required for successful
      cognitive restructuring of trauma memories. This discrepancy may relate to the
      mediating role of both working alliance and cognitive-emotional processing. The
      results underscore the importance of therapists understanding the relationship
      between alliance and other process factors which may be implicit in facilitating
      change.

PMID- 26202462
TI  - Structural basis for recognition of the Sec4 Rab GTPase by its effector, the
      Lgl/tomosyn homologue, Sro7.
AB  - Members of the tomosyn/Lgl/Sro7 family play important roles in vesicle
      trafficking and cell polarity in eukaryotic cells. The yeast homologue, Sro7, is
      believed to act as a downstream effector of the Sec4 Rab GTPase to promote
      soluble N-ethylmaleimide-sensitive factor adaptor protein receptor (SNARE)
      assembly during Golgi-to-cell surface vesicle transport. Here we describe the
      identification of a Sec4 binding site on the surface of Sro7 that is contained
      within a cleft created by the junction of two adjacent beta-propellers that form
      the core structure of Sro7. Computational docking experiments suggested four
      models for interaction of GTP-Sec4 with the Sro7 binding cleft. Further
      mutational and biochemical analyses confirmed that only one of the four docking
      arrangements is perfectly consistent with our genetic and biochemical interaction
      data. Close examination of this docking model suggests a structural basis for the
      high substrate and nucleotide selectivity in effector binding by Sro7. Finally,
      analysis of the surface variation within the homologous interaction site on
      tomosyn-1 and Lgl-1 structural models suggests a possible conserved Rab GTPase
      effector function in tomosyn vertebrate homologues. 

PMID- 26202463
TI  - Silica particles cause NADPH oxidase-independent ROS generation and transient
      phagolysosomal leakage.
AB  - Chronic inhalation of silica particles causes lung fibrosis and silicosis. Silica
      taken up by alveolar macrophages causes phagolysosomal membrane damage and
      leakage of lysosomal material into the cytoplasm to initiate apoptosis. We
      investigated the role of reactive oxygen species (ROS) in this membrane damage by
      studying the spatiotemporal generation of ROS. In macrophages, ROS generated by
      NADPH oxidase 2 (NOX2) was detected in phagolysosomes containing either silica
      particles or nontoxic latex particles. ROS was only detected in the cytoplasm of
      cells treated with silica and appeared in parallel with an increase in phagosomal
      ROS, as well as several hours later associated with mitochondrial production of
      ROS late in apoptosis. Pharmacological inhibition of NOX activity did not prevent
      silica-induced phagolysosomal leakage but delayed it. In Cos7 cells, which do not
      express NOX2, ROS was detected in silica-containing phagolysosomes that leaked.
      ROS was not detected in phagolysosomes containing latex particles. Leakage of
      silica-containing phagolysosomes in both cell types was transient, and after
      resealing of the membrane, endolysosomal fusion continued. These results
      demonstrate that silica particles can generate phagosomal ROS independent of NOX
      activity, and we propose that this silica-generated ROS can cause phagolysosomal
      leakage to initiate apoptosis. 

PMID- 26202464
TI  - The EHD protein Past1 controls postsynaptic membrane elaboration and synaptic
      function.
AB  - Membranes form elaborate structures that are highly tailored to their specialized
      cellular functions, yet the mechanisms by which these structures are shaped
      remain poorly understood. Here, we show that the conserved membrane-remodeling C
      terminal Eps15 Homology Domain (EHD) protein Past1 is required for the normal
      assembly of the subsynaptic muscle membrane reticulum (SSR) at the Drosophila
      melanogaster larval neuromuscular junction (NMJ). past1 mutants exhibit altered
      NMJ morphology, decreased synaptic transmission, reduced glutamate receptor
      levels, and a deficit in synaptic homeostasis. The membrane-remodeling proteins
      Amphiphysin and Syndapin colocalize with Past1 in distinct SSR subdomains and
      collapse into Amphiphysin-dependent membrane nodules in the SSR of past1 mutants.
      Our results suggest a mechanism by which the coordinated actions of multiple
      lipid-binding proteins lead to the elaboration of increasing layers of the SSR
      and uncover new roles for an EHD protein at synapses. 

PMID- 26202465
TI  - Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated
      T-lymphocyte adhesion mediated by integrin alpha4beta1.
AB  - Stimulation by chemokines of integrin alpha4beta1-dependent T-lymphocyte adhesion
      is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for
      chemokine-activated T-cell adhesion mediated by alpha4beta1. Conceivably,
      proteins associating with Vav1 could potentially modulate this adhesion.
      Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to
      alpha4beta1 ligands, a transient stimulation in the association of Vav1 with SLP
      76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or
      Pyk2, or expressing Pyk2 kinase-inactive forms, we show that SLP-76 and ADAP
      stimulate chemokine-activated, alpha4beta1-mediated adhesion, whereas Pyk2
      opposes T-cell attachment. While CXCL12-promoted generation of high-affinity
      alpha4beta1 is independent of SLP-76, ADAP, and Pyk2, the strength of alpha4beta1
      VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by
      these three proteins. GTPase assays, expression of activated or dominant-negative
      Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by
      CXCL12 is a common mediator response in SLP-76-, ADAP-, and Pyk2-regulated cell
      adhesion involving alpha4beta1. Our data strongly suggest that chemokine
      stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation
      and alpha4beta1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting
      Rac1 activation. 

PMID- 26202466
TI  - TPC2 mediates new mechanisms of platelet dense granule membrane dynamics through
      regulation of Ca2+ release.
AB  - Platelet dense granules (PDGs) are acidic calcium stores essential for normal
      hemostasis. They develop from late endosomal compartments upon receiving PDG
      specific proteins through vesicular trafficking, but their maturation process is
      not well understood. Here we show that two-pore channel 2 (TPC2) is a component
      of the PDG membrane that regulates PDG luminal pH and the pool of releasable
      Ca(2+). Using a genetically encoded Ca(2+) biosensor and a pore mutant TPC2, we
      establish the function of TPC2 in Ca(2+) release from PDGs and the formation of
      perigranular Ca(2+) nanodomains. For the first time, Ca(2+) spikes around PDGs-
      or any organelle of the endolysosome family--are visualized in real time and
      revealed to precisely mark organelle "kiss-and-run" events. Further, the presence
      of membranous tubules transiently connecting PDGs is revealed and shown to be
      dramatically enhanced by TPC2 in a mechanism that requires ion flux through TPC2.
      "Kiss-and-run" events and tubule connections mediate transfer of membrane
      proteins and luminal content between PDGs. The results show that PDGs use
      previously unknown mechanisms of membrane dynamics and content exchange that are
      regulated by TPC2.

PMID- 26202467
TI  - A Collaborative Step-Wise Process to Implementing an Innovative Clinic for Adult
      Survivors of Childhood Cancer.
AB  - With a 5 year survival rate of approximately 80%, there is an increasing number
      of childhood cancer survivors in the United States. Childhood cancer survivors
      are at an increased risk for physical and psychosocial health problems many years
      after treatment. Long-term follow-up care should include education, development
      of individualized follow up plans and screening for health problems in accordance
      with the Children's Oncology Group survivor guidelines. Due to survivor, provider
      and healthcare system related barriers, adult survivors of childhood cancer
      (ASCC) infrequently are receiving care in accordance to these guidelines. In this
      paper we describe the stepwise process and collaboration between a children's
      hospital and an adult academic medical center that was implemented to develop the
      Survivorship Transition Clinic and address the needs of ASCC in our region. In
      the clinic model that we designed ASCC follow-up with a primary care physician in
      the adult setting who is knowledgeable about late effects of childhood cancer
      treatment and are provided transition support and education by a transition nurse
      navigator.

PMID- 26202469
TI  - In-vivo degradation of middle-term highly cross-linked and remelted polyethylene
      cups: Modification induced by creep, wear and oxidation.
AB  - In this study Raman (RS) and Fourier Transform Infrared (FT-IR) spectroscopic
      techniques were exploited to study 11 retrieved liners made of remelted highly
      cross-linked polyethylene (HXLPE), with the intent to elucidate their in-vivo
      mechanical and chemical degradation. The retrievals had different follow-ups,
      ranging from a few months to 7 years of implantation time and belong to the first
      generation of highly cross-linked and remelted polyethylene clinically introduced
      in 1999, but still currently implanted. Raman assessments enabled to discriminate
      contributes of wear and creep on the total reduction of thickness in different
      locations of the cup. According to our results, although the most of the
      viscoelastic deformation occurred during the first year (bedding-in period), it
      progressed during the steady wear state up to 7 years with much lower but not
      negligible rate. Overall, the wear rate of this remelted HXLPE liner was low.
      Preliminary analysis on microtomed sections of the liners after in-vivo and in
      vitro accelerated aging (ASTM F2003-02) enabled to obtain a phenomenological
      correlation between the oxidation index (OI) and the amount of orthorhombic phase
      fraction (alphac), which can be easily non-destructively measured by RS. Profiles
      of alphac obtained from different locations of the cups were used to judge the
      oxidative degradation of the 11 retrievals, considering also the ex-vivo time
      elapsed from the revision surgery to the spectroscopic experiments. Low but
      measurable level of oxidation was detected in all the short-term retrievals,
      while in the middle-term samples peaks of OI were observed in the subsurface (up
      to OI=4.5), presumably induced by the combined effect of mechanical stress, lipid
      absorption and prolonged ex-vivo shelf-aging in air. 

PMID- 26202468
TI  - Validation of the UNC TRxANSITION ScaleTMVersion 3 Among Mexican Adolescents With
      Chronic Kidney Disease.
AB  - BACKGROUND: There is a lack of valid health care transition readiness (HCT)
      scales in Spanish. OBJECTIVE: To provide initial validation of the UNC
      TRxANSITION ScaleTM among Mexican adolescents and young adults (youth) with
      chronic kidney disease (CKD). METHODS: We used the professionally translated/back
      translated, provider-administered UNC TRxANSITION ScaleTM (Ferris et al., 2012).
      This 33-question scale measures HCT in ten sub-scales including knowledge about
      diagnosis or treatment, diet, reproductive health, school/work, insurance,
      ability to self-manage and looking for new health providers. Its maximum score is
      10. We enrolled 163 Mexican adolescents (48.5% females) with CKD stage>=3, mean
      age of 15.1years (+/-2.1) and whose primary language is Spanish. There were 15
      patients on hemodialysis (9.2%) and 30 transplant recipients (18.4%). Results
      were compared to those reported in adolescents with chronic conditions from the
      USA. RESULTS: Our cohort's overall median total score was 5.9. Patients>=16years
      old had a median total score of 6.4, whereas younger patients had median score of
      5.6 (p<0.05). Transplant patients had greater scores in the total and the sub
      scales of medication knowledge, issues of reproduction, insurance, trade/work and
      adherence (p<0.05). When comparing the total score (by age), results from our
      Mexican youth were similar to those reported in youth from the USA. CONCLUSIONS:
      In our Mexican cohort of youth with CKD, health care transition readiness is
      greater in older patients and in transplant recipients. Our cohort's overall
      score is low, indicating the need for a health care transition preparation
      program. The UNC TRxANSITION ScaleTM results in Mexican youth with CKD are
      comparable to findings in youth from the USA.

PMID- 26202470
TI  - Novel microstructural findings in M. plantaris and their impact during active and
      passive loading at the macro level.
AB  - There are several studies dealing with experimental and structural analyses of
      skeletal muscles that are aimed at gaining a better understanding of three
      dimensional muscle deformation and force generation. A variety of these
      contributions have performed structural or mechanical analyses, but very few have
      combined these approaches at different levels. To fill this gap, the present
      study aims to bring together three-dimensional micro-structural and mechanical
      findings in rabbit M. plantaris to study load transfer mechanisms inside the
      muscle during passive loading and active muscle contraction. During these two
      deformation states, the three-dimensional surface of the aponeurosis-tendon
      complex was recorded using optical measurement systems. In this way, the strain
      distribution on the muscle can be calculated to interpret the load transfer
      mechanisms inside the muscle. The results show that the three-dimensional strain
      distribution during muscle activation is completely different from the
      distribution during passive loading. Under both loading conditions, the strain
      distribution is irregular. To interpret these findings, the gross try and the
      fascicle architecture of the M. plantaris were determined. In doing so, a highly
      complex microstructure featuring tube- and sail-like structure was identified.
      Moreover, a compartmentalisation of the muscle into two compartments was
      detected. The smaller, bipennated muscle compartment was embedded into the
      larger, unipennated compartment. To the authors' knowledge, this type of inner
      structure has never been previously documented in single-headed muscles.

PMID- 26202471
TI  - Predicting storage-dependent damage to red blood cells using nitrite oxidation
      kinetics, peroxiredoxin-2 oxidation, and hemoglobin and free heme measurements.
AB  - BACKGROUND: Storage-dependent damage to red blood cells (RBCs) varies
      significantly. Identifying RBC units that will undergo higher levels of hemolysis
      during storage may allow for more efficient inventory management decision-making.
      Oxidative-stress mediates storage-dependent damage to RBCs and will depend on the
      oxidant:antioxidant balance. We reasoned that this balance or redox tone will
      serve as a determinant of how a given RBC unit stores and that its assessment in
      "young" RBCs will predict storage-dependent hemolysis. STUDY DESIGN AND METHODS:
      RBCs were sampled from bags and segments stored for 7 to 42 days. Redox tone was
      assessed by nitrite oxidation kinetics and peroxiredoxin-2 (Prx-2) oxidation. In
      parallel, hemolysis was assessed by measuring cell-free hemoglobin (Hb) and free
      heme (hemin). Correlation analyses were performed to determine if Day 7
      measurements predicted either the level of hemolysis at Day 35 or the increase in
      hemolysis during storage. RESULTS: Higher Day 7 Prx-2 oxidation was associated
      with higher Day 35 Prx-2 oxidation, suggesting that early assessment of this
      variable may identify RBCs that will incur the most oxidative damage during
      storage. RBCs that oxidized nitrite faster on Day 7 were associated with the
      greatest levels of storage-dependent hemolysis and increases in Prx-2 oxidation.
      An inverse relationship between storage-dependent changes in oxyhemoglobin and
      free heme was observed underscoring an unappreciated reciprocity between these
      molecular species. Moreover, free heme was higher in the bag compared to paired
      segments, with opposite trends observed for free Hb. CONCLUSION: Measurement of
      Prx-2 oxidation and nitrite oxidation kinetics early during RBC storage may
      predict storage-dependent damage to RBC including hemolysis-dependent formation
      of free Hb and heme.

PMID- 26202473
TI  - Ubiquitous distribution of helmchrome in phototactic swarmers of the
      stramenopiles.
AB  - Most swarmers (swimming cells) of the stramenopile group, ranging from
      unicellular protist to giant kelps (brown algae), have two heterogeneous
      flagella: a long anterior flagellum (AF) and a relatively shorter posterior
      flagellum (PF). These flagellated cells often exhibit phototaxis upon light
      stimulation, although the mechanism by which how the phototactic response is
      regulated remains largely unknown. A flavoprotein concentrating at the
      paraflagellar body (PFB) on the basal part of the PF, which can emit green
      autofluorescence under blue light irradiance, has been proposed as a possible
      blue light photoreceptor for brown algal phototaxis although the nature of the
      flavoprotein still remains elusive. Recently, we identified helmchrome as a PF
      specific flavoprotein protein in a LC-MS/MS-based proteomics study of brown algal
      flagella (Fu et al. 2014). To verify the conservation of helmchrome, in the
      present study, the absence or presence and the localization of helmchrome in
      swarmers of various algal species were investigated. The results showed that
      helmchrome was only detected in phototactic swarmers but not the non-phototactic
      ones of the stramenopile group. Electron microscopy further revealed that the
      helmchrome detectable swarmers bear a conserved PFB-eyespot complex, which may
      serve as structural basis for light sensing. It is speculated that all three
      conserved properties: helmchrome, the PFB structure, and the eyespot apparatus,
      will be essential parts for phototaxis of stramenopile swarmers. 

PMID- 26202474
TI  - Genome-wide association QTL mapping for teat number in a purebred population of
      Duroc pigs.
AB  - Because of increasing litter size in Western pig breeds, additional teats are
      desirable to increase the capacity for nursing offspring. We applied genome-wide
      SNP markers to detect QTL regions that affect teat number in a Duroc population.
      We phenotyped 1024 animals for total teat number. A total of 36 588 SNPs on
      autosomes were used in the analysis. The estimated heritability for teat number
      was 0.34 +/- 0.05 on the basis of a genomic relationship matrix constructed from
      all SNP markers. Using a BayesC method, we identified a total of 18 QTL regions
      that affected teat number in Duroc pigs; 9 of the 18 regions were newly detected.

PMID- 26202476
TI  - Nucleoside uptake in Vibrio cholerae and its role in the transition fitness from
      host to environment.
AB  - As it became evident recently, extracellular DNA could be a versatile nutrient
      source of the facultative pathogen Vibrio cholerae along the different stages of
      its life cycle. By the use of two extracellular nucleases and periplasmic
      phosphatases, V. cholerae degrades extracellular DNA to nucleosides. In this
      study, we investigated the nucleoside uptake via identification and
      characterization of VCA0179, VC1953 and VC2352 representing the three nucleoside
      transport systems in V. cholerae. Based on our results VC2352 seems to be the
      dominant nucleoside transporter. Nevertheless, all three transporters are
      functional and can contribute to the utilization of nucleosides as a sole source
      of carbon or nitrogen. We found that the transcriptional activity of these three
      distal genes is equally promoted or antagonized by CRP or CytR respectively.
      Finally, mutants impaired for nucleoside uptake exhibit decreased transition
      fitness from the host into low carbon environments along the life cycle of V.
      cholerae.

PMID- 26202475
TI  - Anion-Responsive Metallopolymer Hydrogels for Healthcare Applications.
AB  - Metallopolymers combine a processable, versatile organic polymeric skeleton with
      functional metals, providing multiple functions and methodologies in materials
      science. Taking advantage of cationic cobaltocenium as the key building block,
      organogels could be simply switched to hydrogels via a highly efficient ion
      exchange. With the unique ionic complexion ability, cobaltocenium moieties
      provide a robust soft substrate for recycling antibiotics from water. The
      essential polyelectrolyte nature offers the metallopolymer hydrogels to kill
      multidrug resistant bacteria. The multifunctional characteristics of these
      hydrogels highlight the potential for metallopolymers in the field of healthcare
      and environmental treatment. 

PMID- 26202477
TI  - A Novel Bio-carrier Fabricated Using 3D Printing Technique for Wastewater
      Treatment.
AB  - The structure of bio-carriers is one of the key operational characteristics of a
      biofilm reactor. The goal of this study is to develop a series of novel fullerene
      type bio-carriers using the three-dimensional printing (3DP) technique. 3DP can
      fabricate bio-carriers with more specialized structures compared with traditional
      fabrication processes. In this research, three types of fullerene-type bio
      carriers were fabricated using the 3DP technique and then compared with bio
      carrier K3 (from AnoxKaldnes) in the areas of physicochemical properties and
      biofilm growth. Images acquired by 3D profiling and SEM indicated that the
      surface roughness of the 3DP bio-carrier was greater than that of K3.
      Furthermore, contact angle data indicated that the 3DP bio-carriers were more
      hydrophilic than K3. The biofilm on the 3DP bio-carriers exhibited higher
      microbial activity and stronger adhesion ability. These findings were attributed
      to excellent mass transfer of the substrate (and oxygen) between the vapour
      liquid-solid tri-phase system and to the surface characteristics. It is concluded
      that the novel 3DP fullerene-type bio-carriers are ideal carriers for biofilm
      adherence and growth. 

PMID- 26202478
TI  - Genetic polymorphism of miR-146a is associated with gastric cancer risk: a meta
      analysis.
AB  - Several studies have investigated the associations between miR-146a rs2910164 and
      gastric cancer (GC) risk, but results have been inconclusive. To derive a more
      precise estimation of the relationship, a meta-analysis was performed. PubMed and
      China National Knowledge Infrastructure searches were carried out for relevant
      studies published before July 2014. Meta-analysis was performed with the stata,
      version 11.0. A total of seven case-control studies, including 3283 cases and
      4535 controls, were selected. A significant association was found between
      rs2910164 and GC risk under all genetic models (CC vs. GG, OR = 0.76, 95% CI =
      0.66-0.87; CC vs. GC+GG, OR = 0.84, 95% CI = 0.71-0.99; CC+GC vs. GG, OR = 0.82,
      95% CI = 0.73-0.91) for the total data. In the subgroup analysis by ethnicity,
      statistically significant association was found in Asian. This meta-analysis
      suggested that the miR-146a rs2910164 was a risk factor for developing GC.

PMID- 26202480
TI  - Prevalence of Metatarsus Adductus in Symptomatic Hallux Valgus and Its Influence
      on Functional Outcome.
AB  - BACKGROUND: Metatarsus adductus (MA) increases the risk of developing symptomatic
      hallux valgus (HV). This study aimed to determine the prevalence of MA in
      patients with symptomatic HV and to evaluate how it affected the functional
      outcome after scarf osteotomy. METHODS: Between January 2007 and June 2012, a
      total of 206 patients who underwent scarf osteotomy for symptomatic HV at a
      tertiary hospital were included. The metatarsus adductus angle (MAA) was
      determined using the Modified Sgarlato method, and these patients were
      categorized into 2 groups: MA (MAA > 20 degrees); and Control (MAA <= 20
      degrees). The patients were prospectively followed for 2 years. RESULTS: The
      prevalence of MA was 33% (68/206) with a mean MAA of 24 +/- 4 degrees (range = 20
      39). There was a 21 +/- 12 degrees and 18 +/- 9 degrees improvement in hallux
      valgus angle for the MA and Control groups, respectively (P = .061), whereas
      there was a 6 +/- 4 degrees and 6 +/- 3 degrees improvement in intermetartarsal
      angle for the MA and Control groups, respectively (P = .475). The visual analog
      scale, AOFAS Hallux Metatarsophalangeal-Interphalangeal Scale, and Physical and
      Mental Component Scores were comparable between the 2 groups both preoperatively
      and at 2 years' follow-up (all P > .05). Two patients in the control group
      required revision surgery for recurrence symptomatic HV. CONCLUSION: The authors
      conclude that MA did not predispose the patient to poorer functional outcome
      after scarf osteotomy with the advent of good operative techniques. LEVEL OF
      EVIDENCE: Level II, prospective comparative study.

PMID- 26202481
TI  - Negative feedback circuit for toll like receptor-8 activation in human embryonic
      Kidney 293 using outer membrane vesicle delivered bi-specific siRNA.
AB  - BACKGROUND: TLR8 assists in antiviral approach by producing Type 1 INF via MyD88
      dependent IRF7 pathway. However, over expression of INFalpha/beta molecule poses
      threat by developing tolerance in chronic infection cases and enhancing
      inflammatory response. Here we report a bi-specific siRNA based complex which
      differentially activates and silences the TLR8 and MYD88 respectively in a
      negatively regulated fashion. RESULTS: Outer membrane vesicle from Escherichia
      coli used for siRNA delivery was observed more efficient when attached with
      invasive protein Ail along with OmpA (P<0.001) in HEK293-TLR8 cell line. siRNA
      complexed with p19 protein was efficient in activating TLR8, confirmed by the
      increment of INFbeta molecules (P<0.001) in HEK293-TLR8 compared to its
      counterpart. Fusion of lipid bilayer of endosomal compartment was significant at
      pH 4.5 when fusogenic peptides (diINF-7) were incubated in membrane vesicle, thus
      facilitating the escape of siRNA complex to the host cytoplasm in order to
      silence MyD88 transcript (P<0.001). CONCLUSIONS: We investigated the activation
      of TLR8 by bi-specific si-RNA for the production of INFbeta. In the same setting
      we showed that bi-specific si-RNA was able to silence MyD88 transcript in a
      delayed manner. For the cases of auto immune disease and inflammation where over
      activation of endosomal TLRs poses serious threat, bi specific siRNA could be
      used as negative feedback controlled system.

PMID- 26202482
TI  - Engineering of alanine dehydrogenase from Bacillus subtilis for novel cofactor
      specificity.
AB  - The l-alanine dehydrogenase of Bacillus subtilis (BasAlaDH), which is strictly
      dependent on NADH as redox cofactor, efficiently catalyzes the reductive
      amination of pyruvate to l-alanine using ammonia as amino group donor. To enable
      application of BasAlaDH as regenerating enzyme in coupled reactions with NADPH
      dependent alcohol dehydrogenases, we alterated its cofactor specificity from NADH
      to NADPH via protein engineering. By introducing two amino acid exchanges, D196A
      and L197R, high catalytic efficiency for NADPH was achieved, with kcat /KM  =
      54.1 uM-1  Min-1 (KM  = 32 +/- 3 uM; kcat  = 1,730 +/- 39 Min-1 ), almost the
      same as the wild-type enzyme for NADH (kcat /KM  = 59.9 uM-1  Min-1 ; KM  = 14 +/
      2 uM; kcat  = 838 +/- 21 Min-1 ). Conversely, recognition of NADH was much
      diminished in the mutated enzyme (kcat /KM  = 3 uM-1  Min-1 ).
      BasAlaDH(D196A/L197R) was applied in a coupled oxidation/transamination reaction
      of the chiral dicyclic dialcohol isosorbide to its diamines, catalyzed by
      Ralstonia sp. alcohol dehydrogenase and Paracoccus denitrificans omega
      aminotransferase, thus allowing recycling of the two cosubstrates NADP+ and l
      Ala. An excellent cofactor regeneration with recycling factors of 33 for NADP+
      and 13 for l-Ala was observed with the engineered BasAlaDH in a small-scale
      biocatalysis experiment. This opens a biocatalytic route to novel building blocks
      for industrial high-performance polymers.

PMID- 26202483
TI  - Bird and bat predation services in tropical forests and agroforestry landscapes.
AB  - Understanding distribution patterns and multitrophic interactions is critical for
      managing bat- and bird-mediated ecosystem services such as the suppression of
      pest and non-pest arthropods. Despite the ecological and economic importance of
      bats and birds in tropical forests, agroforestry systems, and agricultural
      systems mixed with natural forest, a systematic review of their impact is still
      missing. A growing number of bird and bat exclosure experiments has improved our
      knowledge allowing new conclusions regarding their roles in food webs and
      associated ecosystem services. Here, we review the distribution patterns of
      insectivorous birds and bats, their local and landscape drivers, and their
      effects on trophic cascades in tropical ecosystems. We report that for birds but
      not bats community composition and relative importance of functional groups
      changes conspicuously from forests to habitats including both agricultural areas
      and forests, here termed 'forest-agri' habitats, with reduced representation of
      insectivores in the latter. In contrast to previous theory regarding trophic
      cascade strength, we find that birds and bats reduce the density and biomass of
      arthropods in the tropics with effect sizes similar to those in temperate and
      boreal communities. The relative importance of birds versus bats in regulating
      pest abundances varies with season, geography and management. Birds and bats may
      even suppress tropical arthropod outbreaks, although positive effects on plant
      growth are not always reported. As both bats and birds are major agents of pest
      suppression, a better understanding of the local and landscape factors driving
      the variability of their impact is needed.

PMID- 26202484
TI  - A spiralling origin of the median nerve around an accessory coracobrachialis
      brevis muscle.
AB  - During an ultrasound-guided axillary brachial plexus block, sonoanatomy
      demonstrated a delayed formation of the lateral root to the median nerve from the
      lateral cord, an accessory coracobrachialis brevis muscle, and a course of the
      lateral root to the median nerve 'spiralling' around the accessory muscle prior
      to locating lateral to the brachial artery. This rare variant is further
      discussed in the context of median, musculocutaneous and coracobrachialis
      variations. 

PMID- 26202485
TI  - Vibrational Raman Shifts and Aromaticity: The Case of Oligothiophenes.
AB  - A general description of the use of the Raman spectra of polyconjugated molecules
      to infer their electronic and molecular properties and how these change in a
      number of situations is illustrated with several examples, with particular
      emphasis on oligothiophene molecules. The most noticeable features of the Raman
      spectra of these molecules and the main theoretical models developed for their
      understanding have been revised and explained in terms related to pi-electron
      delocalization intimately connected with the aromatic and quinoidal characters. 

PMID- 26202486
TI  - Estimating the tendency of motor unit recruitment during steady-hold and rapid
      contractions using surface EMG and Turns-amplitude analysis.
AB  - PURPOSE: The purpose of this study was to investigate changes in the interference
      pattern in surface electromyography (EMG), and its relationship with the tendency
      of motor unit (MU) recruitment during steady-hold and rapid muscle contractions.
      METHODS: Fifteen healthy adults (eight females and seven males, 22.6 +/- 1.5
      years old) performed steady-hold and rapid isometric contractions of the bicep
      brachii, adductor pollicis, and tibialis anterior muscles at various force
      levels. Surface EMG recordings were analyzed using Turns-Amplitude Analysis
      (TAA). RESULTS: During steady-hold contractions, the number of turns per second
      (T/s) increased exponentially with force during submaximal contractions, and
      plateaued after force levels of 66, 70 and 57 % MVC for the tibialis anterior,
      bicep brachii and adductor pollicis muscles, respectively. These force levels
      were proximate to the maximal recruitment threshold (MaxRT) reported previously.
      The slopes of the T/s-force relationships before the MaxRT were significantly
      greater than the slopes after the MaxRT for all three muscles tested. During
      rapid contraction, the slopes of the T/s-force relationships were significantly
      lower than the slopes of the steady-hold contraction at 20-40 % MVC in all three
      muscles, and for 40-60 % MVC in TA muscles. CONCLUSIONS: Our results suggested
      that the changes in the number of turns in surface EMG with respect to muscle
      force can be used to estimate the force levels at which the majority of the MUs
      to be recruited, and completion of MU recruitment was observed at lower force
      levels during rapid muscle contraction.

PMID- 26202487
TI  - Effect of whole-body vibration training on bone mass in adolescents with and
      without Down syndrome: a randomized controlled trial.
AB  - Whole-body vibration training (WBV) attracts great interest as osteoporosis
      prevention strategy. Twenty-six adolescents with and without Down syndrome (DS)
      (13 DS; 12-18 years) performed 20 weeks of WBV. The results indicate that WBV
      seems to provoke a lesser response in adolescents with DS than in those without
      DS. INTRODUCTION: This study aims to observe the differences between adolescents
      with and without DS in the effects of 20 weeks of WBV training, on bone mineral
      content (BMC) and density (BMD). METHODS: Twenty-six adolescents (13 DS; 12-18
      years) were measured with dual-energy X-ray absorptiometry before and after the
      intervention (3/week, 10 repetitions (30-60 s) and 1-min rest, frequency 25-30 Hz
      and peak-to-peak displacement of 2 mm (peak acceleration 2.5-3.6 g)). Both, an
      intention-to-treat (ITT) analysis designed to assess the effects on bone mass and
      a per-protocol analysis, designed to compare poor and high compliers, were
      performed. RESULTS: The ITT analysis revealed significant increases in all BMC
      and BMD parameters (dz = 0.66 to 1.64; all p < 0.05) in the non-DS group, whilst
      DS group improved whole-body, subtotal (whole-body less head), upper limbs
      (ULIMBS), pelvis, lower limbs (LLIMBS) and spine BMC (dz = 0.75 to 1.76; all p <
      0.05) and subtotal, pelvis, LLIMBS and spine BMD (dz = 0.73 to 1.28; all p <
      0.05). Significantly greater increases were evident in the absolute and percent
      changes of the non-DS group over DS group (d = 0.88 to 3.85; all p < 0.05).
      ULIMBS BMD showed a tendency towards an interaction (f = 0.41 and p = 0.086) with
      higher increase for non-DS group. When a per-protocol analysis was considered,
      high-complier adolescents had 8.1 versus 5.3 % of gains in the spine BMC over
      poor-complier adolescents (d = 0.93; p < 0.05). CONCLUSIONS: Twenty weeks of WBV
      training may improve BMC and BMD in clinically relevant skeletal sites in both
      groups. Nevertheless, this type of training seems to provoke a lesser response in
      adolescents with DS than in those without DS.

PMID- 26202488
TI  - The effect of 8 or 5 years of denosumab treatment in postmenopausal women with
      osteoporosis: results from the FREEDOM Extension study.
AB  - The FREEDOM study and its Extension provide long-term information about the
      effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment
      for up to 8 years was associated with persistent reduction of bone turnover,
      continued increases in bone mineral density, low fracture incidence, and a
      favorable benefit/risk profile. INTRODUCTION: This study aims to report the
      results through year 5 of the FREEDOM Extension study, representing up to 8 years
      of continued denosumab treatment in postmenopausal women with osteoporosis.
      METHODS: Women who completed the 3-year FREEDOM study were eligible to enter the
      7-year open-label FREEDOM Extension in which all participants are scheduled to
      receive denosumab, since placebo assignment was discontinued for ethical reasons.
      A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross
      over). In this analysis, women in the long-term and cross-over groups received
      denosumab for up to 8 and 5 years, respectively. RESULTS: Throughout the
      Extension, sustained reduction of bone turnover markers (BTMs) was observed in
      both groups. In the long-term group, mean bone mineral density (BMD) continued to
      increase significantly at each time point measured, for cumulative 8-year gains
      of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross
      over group, mean BMD increased significantly from the Extension baseline for 5
      year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip,
      respectively. The yearly incidence of new vertebral and nonvertebral fractures
      remained low in both groups. The incidence of adverse and serious adverse events
      did not increase over time. Through Extension year 5, eight events of
      osteonecrosis of the jaw and two events of atypical femoral fracture were
      confirmed. CONCLUSIONS: Denosumab treatment for up to 8 years was associated with
      persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a
      consistent safety profile.

PMID- 26202490
TI  - Erratum to: High fracture probability predicts fractures in a 4-year follow-up in
      women from the RAC-OST-POL study.

PMID- 26202489
TI  - Does bisphosphonate-based anti-osteoporosis medication affect osteoporotic spinal
      fracture healing?
AB  - Effects of bisphosphonate on fracture healing were prospectively investigated for
      osteoporotic spinal fracture. Although there were no significant differences in
      clinical outcomes, the presence of intravertebral cleft was related to the
      medication use. These results suggest that suspension of bisphosphonate use
      should be considered during the fracture healing period. INTRODUCTION: The
      purpose of this prospective study is to investigate whether bisphosphonate-based
      anti-osteoporosis medication affects fracture healing and clinical outcomes of
      conservatively treated osteoporotic spinal fractures (OSFs). METHODS: A total of
      105 patients who were diagnosed with acute OSFs were prospectively enrolled.
      According to their previous medication history, the patients were allocated into
      group I (n = 39, no history of bisphosphonate use) or group II (n = 66, history
      of bisphosphonate use). Clinical outcomes were assessed using visual analogue
      scale (VAS), and Oswestry disability index (ODI). Radiographic parameters
      including changes in height loss and kyphotic angle at the index vertebra were
      measured, and radiographic findings suggesting impaired fracture healing such as
      the intravertebral cleft (IVC) sign and fracture instability were evaluated.
      Univariate and multivariate regression analyses were used to identify related
      factors. RESULTS: There were no significant differences in the last VAS and ODI
      between groups. There were also no significant differences in the radiographic
      parameters. Although the IVC sign was seen more commonly in group II (30.3 %)
      than in group I (20.5 %), fracture instability combined with IVC was noted in the
      same number of cases. On multiple regression analysis, medication history showed
      no significant relationship with the clinical parameters. However, the presence
      of the IVC sign was related to medication history (odds ratio 4.8; 95 %
      confidence interval [CI] 1.02-22.69). CONCLUSIONS: Bisphosphonate use does not
      significantly affect the clinical results during conservative treatment for OSFs.
      However, the occurrence of the IVC sign was related to medication history.
      Although further studies are needed to verify our findings, these results suggest
      that suspension of bisphosphonate use should be considered during the fracture
      healing period for acute OSFs.

PMID- 26202491
TI  - BRHIS1 suppresses rice innate immunity through binding to monoubiquitinated H2A
      and H2B variants.
AB  - In the absence of pathogen attack, organisms usually suppress immune responses to
      reduce the negative effects of disease resistance. Monoubiquitination of histone
      variants at specific gene loci is crucial for gene expression, but its
      involvement in the regulation of plant immunity remains unclear. Here, we show
      that a rice SWI/SNF2 ATPase gene BRHIS1 is downregulated in response to the rice
      blast fungal pathogen or to the defense-priming-inducing compound BIT (1,2
      benzisothiazol-3(2h)-one,1, 1-dioxide). The BRHIS1-containing complex represses
      the expression of some disease defense-related genes, including the pathogenesis
      related gene OsPBZc and the leucine-rich-repeat (LRR) receptor-like protein
      kinase gene OsSIRK1. This is achieved through BRHIS1 recruitment to the promoter
      regions of target genes through specific interaction with monoubiquitinated
      histone variants H2B.7 and H2A.Xa/H2A.Xb/H2A.3, in the absence of pathogen attack
      or BIT treatment. Our results show that rice disease defense genes are initially
      organized in an expression-ready state by specific monoubiquitination of H2A and
      H2B variants deposited on their promoter regions, but are kept suppressed by the
      BRHIS1 complex, facilitating the prompt initiation of innate immune responses in
      response to infection through the stringent regulation of BRHIS1. 

PMID- 26202492
TI  - Heterogeneous Expression and Functional Characterization of Cellulose-Degrading
      Enzymes from Aspergillus niger for Enzymatic Hydrolysis of Alkali Pretreated
      Bamboo Biomass.
AB  - Enzymatic hydrolysis of cellulosic biomass has caught much attention because of
      modest reaction conditions and environment friendly conditions. To reduce the
      cost and to achieve good quantity of cellulases, a heterologous expression system
      is highly favored. In this study, cellulose-degrading enzymes, GH3 family beta
      glucosidase (BGL), GH7 family-related cellobiohydrolases (CBHs), and
      endoglucanase (EG) from a newly isolated Aspergillus niger BE-2 are highly
      expressed in Pichia pastoris GS115. The strain produced EG, CBHs, and BGL
      enzymatic concentration of 0.56, 0.11, and 22 IU/mL, respectively. Mode of
      actions of the recombinant enzymes for substrate specificity and end product
      analysis are verified and found specific for cellulose degradation. Bamboo
      biomass saccharification with A. niger cellulase released a high level of
      fermentable sugars. Hydrolysis parameters are optimized to obtain reducing sugars
      level of 3.18 g/L. To obtain reducing sugars from a cellulosic biomass, A. niger
      could be a good candidate for enzymes resource of cellulase to produce reducing
      sugars from a cellulosic biomass. This study also facilitates the development of
      highly efficient enzyme cocktails for the bioconversion of lignocellulosic
      biomass into monosaccharides and oligosaccharides. 

PMID- 26202493
TI  - Increased Heterologous Protein Expression in Drosophila S2 Cells for Massive
      Production of Immune Ligands/Receptors and Structural Analysis of Human HVEM.
AB  - Many immune ligands and receptors are potential drug targets, which delicately
      manipulate a wide range of immune responses. We describe here the successful
      application of an efficient method to dramatically improve the heterologous
      expression levels in Drosophila Schneider 2 cells, which enables the high
      throughput production of several important immune ligands/receptors for raising
      antibodies, and for the structural and functional analyses. As an example, we
      purified the protein and characterized the structure of the immune receptor
      herpesvirus entry mediator (HVEM, TNFRSF14). HVEM is a member of tumor necrosis
      factor receptor superfamily, which is recognized by herpes simplex virus
      glycoprotein D (gD) and facilitates viral entry. HVEM participates in a range of
      interactions with other cell surface molecules, including LIGHT, BTLA, and CD160
      to modulate a wide range of immune processes in CD4(+) and CD8(+) T cells, as
      well as NK cells. Due to the involvement of HVEM in these diverse signaling
      interactions, crystal structures of HVEM in complex with gD or BTLA have been
      previously reported. Here, we report the structure of HVEM in the absence of any
      ligands. 

PMID- 26202494
TI  - Exploring the Feasibility of the Sec Route to Secrete Proteins Using the Tat
      Route in Streptomyces lividans.
AB  - Streptomyces lividans uses mainly two pathways to target secretory proteins to
      the cytoplasmic membrane. The major pathway (Sec pathway) transports pre-proteins
      using the signal recognition particle, and the minor Tat pathway is responsible
      for the secretion using a folded conformation of a relatively low number of
      proteins. The signal peptides of the Sec-dependent alpha-amylase and the Tat
      dependent agarase were interchanged and fused in-frame to the corresponding
      mature part of the other enzyme. Alpha-amylase was unable to use the Tat route
      when fused to the agarase signal peptide, while agarase used the Sec route when
      it was targeted by the alpha-amylase signal peptide. In addition to the signal
      peptide some yet unidentified parts of the secreted proteins may play a role in
      selecting the secretory route. Structure predictions for the Tat- and Sec
      dependent proteins suggest that less structured proteins are more likely to be
      candidates for the Tat route. 

PMID- 26202495
TI  - Ultra Wideband Polarization-Selective Conversions of Electromagnetic Waves by
      Metasurface under Large-Range Incident Angles.
AB  - We propose an ultra-wideband polarization-conversion metasurface with
      polarization selective and incident-angle insensitive characteristics using
      anchor-shaped units through multiple resonances. The broadband characteristic is
      optimized by the genetic optimization algorithm, from which the anchor-shaped
      unit cell generates five resonances, resulting in expansion of the operating
      frequency range. Owing to the structural feature of the proposed metasurface,
      only x- and y-polarized incident waves can reach high-efficiency polarization
      conversions, realizing the polarization-selective property. The proposed
      metasurface is also insensitive to the angle of incident waves, which indicates a
      promising future in modern communication systems. We fabricate and measure the
      proposed metasurface, and both the simulated and measured results show ultra-wide
      bandwidth for the x- and y-polarized incident waves. 

PMID- 26202496
TI  - No strong association is found between pioglitazone and bladder cancer.

PMID- 26202497
TI  - Interferon graft dysfunction: a final chapter for interferon and hepatitis C.

PMID- 26202498
TI  - Cell therapies and regenerative medicine.
AB  - Molecular and cell biology has resulted in major advances in our understanding of
      disease pathogenesis as well as in novel strategies for the diagnosis, therapy
      and prevention of human diseases. Based on modern molecular, genetic and
      biochemical methodologies, it is on the one hand possible to identify disease
      related point mutations and single nucleotide polymorphisms, for example. On the
      other hand, using high throughput array and other technologies, it is for example
      possible to simultaneously analyze thousands of genes or gene products (RNA and
      proteins), resulting in an individual gene or gene expression profile
      ('signature'). Such data increasingly allow defining the individual disposition
      for a given disease and predicting disease prognosis as well as the efficacy of
      therapeutic strategies in the individual patient ('personalized medicine'). At
      the same time, the basic discoveries in cell biology, including embryonic and
      adult stem cells, induced pluripotent stem cells, genetically modified cells and
      others, have moved regenerative medicine into the center of biomedical research
      worldwide with a major translational impact on tissue engineering as well as
      transplantation medicine. All these aspects have greatly contributed to the
      recent advances in regenerative medicine and the development of novel concepts
      for the treatment of many human diseases, including liver diseases. 

PMID- 26202499
TI  - Bone marrow stem-cell therapy for genetic and chronic liver diseases.
AB  - There are no permanent remedies for patients suffering from genetic liver
      diseases (GLDs) and liver cirrhosis (LC). In such cases, liver transplantation
      has resulted in improved quality of life, but it is not affordable by most
      patients. Therefore, a cost-effective, safe, and permanent cure for these
      diseases is desirable. Cell therapy seems an encouraging option for treatment of
      these liver diseases in the future. Animal experiments and clinical studies have
      demonstrated that, depending on the nature of the liver disease and the patient,
      autologous and/or allogeneic bone marrow (BM)-derived stem-cell therapy could be
      a promising treatment option. Although no clinical trials using BM-derived stem
      cells for treatment of GLD have yet been conducted, many phase I clinical trials
      have been conducted and a few such trials for the treatment of LC by use of
      autologous and/or allogeneic cells are in progress. Overall, the results of these
      trials are indicative of clinical benefits with no adverse effect on the
      patients. This review focuses on the current status of BM stem-cell therapy for
      treatment of GLD and LC in experimental animals and human subjects. It also
      proposes safer approaches to immune-regulation in allogeneic transplantation of
      cells. 

PMID- 26202500
TI  - MSC-based therapies in solid organ transplantation.
AB  - Immunomodulatory cell therapy as a complement to standard pharmacotherapy
      represents a novel approach to solid organ allograft acceptance. This methodology
      may allow for a reduced dose of immunosuppressive drug to be administered and
      thus attenuate the severe side effects associated with long-term
      immunosuppression such as drug-related impairment of renal function, increased
      risk from opportunistic infections and malignancies. Mesenchymal stem cells
      (MSCs) have been shown to possess both immune modulatory and regenerative
      properties in vitro and in preclinical models. Encouraging results have been
      reported from studies examining the safety and efficacy of MSCs as a treatment
      for acute graft-versus-host disease. MSCs represent a promising candidate cell
      therapy to supplement immunosuppression in recipients of solid organs, and
      initial reports on the clinical use of MSCs in kidney transplantation have been
      recently published (Tan et al. in J Am Med Assoc 307:1169-1177, 2012; Reinders et
      al. in Stem Cells Transl Med 2:107-111, 2013; Perico et al. in Transpl Int 26:867
      878, 2013; Perico et al. in Clin J Am Soc Nephrol 6:412-422, 2011). An area of
      even greater interest might be the application of MSCs in clinical liver
      transplantation as graft survival is closely associated with overall patient
      survival. Here, we present preclinical findings and discuss their possible impact
      on clinical liver transplantation. Then we discuss clinical studies designed to
      investigate how MSCs may be distributed and act in solid organ transplantation. 

PMID- 26202502
TI  - Comparison of hepatitis B surface antigen and e antigen in predicting liver
      histology in hepatitis B e antigen-positive chronic hepatitis B patients.
AB  - BACKGROUND/AIM: The purpose of this study was to determine the relationship
      between hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg)
      levels and liver histology in HBeAg-positive patients with chronic hepatitis B
      virus (CHB) infection. METHODS: Serum HBsAg and HBeAg levels were analyzed, and
      liver biopsies were obtained from 203 HBeAg-positive CHB patients (62.6 % males;
      median age 31.3 years). The upper limit of normal (ULN) for ALT in this study was
      30 and 19 U/L for males and females, respectively. Histologic assessment was
      based on Scheuer classification. RESULTS: ALT <2 * ULN, fibrosis stage <S2, and
      necro-inflammation grade <G2 were noted in 70 (34.5 %), 141 (69.5 %), and 105
      (51.7 %) patients, respectively. Patients with significant histology (fibrosis
      stage >=S2 and/or fibrosis stage of 1 plus inflammation grade >=2) had
      significantly lower median HBsAg (13,998.4 and 42,186.5 IU/mL, respectively, p <
      0.001) and HBeAg levels (540.5 and 1,206.8 S/CO, respectively, p < 0.001) than
      patients with insignificant histology. Among patients with ALT <2 * ULN, the area
      under the ROC curve for serum HBsAg and HBeAg levels was 0.76 and 0.70,
      respectively. Using a cutoff value of 17,558 IU/mL for HBsAg and 875.6 S/CO for
      HBeAg in patients with ALT <2*ULN, positive predictive values for insignificant
      histology were 87 and 86.8 %, respectively, whereas the negative predictive
      values were 50 and 47.1 %, respectively. CONCLUSIONS: Among HBeAg-positive
      patients with ALT <2 * ULN, high-serum HBsAg and HBeAg levels can equally
      accurately predict insignificant histology.

PMID- 26202501
TI  - Biomaterials for liver tissue engineering.
AB  - Liver extracellular matrix (ECM) composition, topography and biomechanical
      properties influence cell-matrix interactions. The ECM presents guiding cues for
      hepatocyte phenotype maintenance, differentiation and proliferation both in vitro
      and in vivo. Current understanding of such cell-guiding cues along with
      advancement of techniques for scaffold fabrication has led to evolution of
      matrices for liver tissue culture from simple porous scaffolds to more complex 3D
      matrices with microarchitecture similar to in vivo. Natural and synthetic
      polymeric biomaterials fabricated in different topographies and porous matrices
      have been used for hepatocyte culture. Heterotypic and homotypic cell
      interactions are necessary for developing an adult liver as well as an artificial
      liver. A high oxygen demand of hepatocytes as well as graded oxygen distribution
      in liver is another challenging attribute of the normal liver architecture that
      further adds to the complexity of engineered substrate design. A balanced
      interplay of cell-matrix interactions along with cell-cell interactions and
      adequate supply of oxygen and nutrient determines the success of an engineered
      substrate for liver cells. Techniques devised to incorporate these features of
      hepatic function and mimic liver architecture range from maintaining liver cells
      in mm-sized tailor-made scaffolds to a more bottoms up approach that starts from
      building the microscopic subunit of the whole tissue. In this review, we discuss
      briefly various biomaterials used for liver tissue engineering with respect to
      design parameters such as scaffold composition and chemistry, biomechanical
      properties, topography, cell-cell interactions and oxygenation. 

PMID- 26202503
TI  - Hepatitis C viremia interferes with serum hepatitis B virus surface antigen and
      DNA levels in hepatitis B uremics.
AB  - PURPOSE: Hepatitis B virus (HBV) and HCV might cause reciprocal interference. We
      aimed to elucidate the influence of HCV and interleukin-28B (IL-28B) genetic
      variants in the HBV DNA and HBsAg levels in uremic HBV carriers. METHODS:
      Assessment of HCV and HBV viral loads, HBsAg levels and IL-28B genotype were
      performed in 229 HBsAg-positive patients from a cohort of 1,681 uremics. RESULTS:
      Patients with HCV viremia had significantly lower HBV DNA (2.58 +/- 0.80 vs. 3.16
      +/- 1.48 log IU/mL, p = 0.005) and HBsAg levels (1.33 +/- 1.35 vs. 2.23 +/- 1.31
      log IU/mL, p = 0.002) compared with those without. IL-28B rs8099917 genotype had
      no impact on HBsAg and HBV DNA levels. In multivariate regression analysis, HCV
      RNA levels had a more significant negative correlation with HBsAg levels [beta 
      0.905; 95 % confidence interval (CI) -1.477, -0.334; p = 0.002] than with HBV DNA
      levels (beta -0.586; 95 % CI -1.206, 0.034; p = 0.06). The serum HBV DNA and
      HBsAg levels had a positive correlation (r = 0.43, p < 0.001) among the 215 HBeAg
      negative patients. However, the correlation was not observed in patients with HCV
      viremia (r = 0.23, p = 0.29). Linear regression analysis revealed that age (beta 
      0.286; 95 % CI -0.043, -0.014; p < 0.001) and the HBV DNA level (beta 0.373; 95 %
      CI 0.239, 0.549; p < 0.001) correlated independently with the HBsAg level among
      HBeAg-negative patients without HCV viremia, but not among those with concomitant
      HCV viremia. CONCLUSIONS: HCV viremia suppressed both HBsAg and HBV DNA levels.
      The HBsAg levels correlated with the HBV DNA levels only in patients without
      concomitant HCV viremia.

PMID- 26202504
TI  - Opportunistic infection in patients with acute liver failure.
AB  - BACKGROUND: Treatment with systemic corticosteroids is often used for acute liver
      failure (ALF), but this has increased the number of profoundly immunocompromised
      patients and cases of opportunistic infection. METHODS: Between January 2007 and
      December 2012, all patients (n = 51) referred to the Chiba University Hospital
      for treatment of ALF were studied. Patients with prothrombin activity of 40 % or
      less of the standardized values were defined as having ALF. Patient age, sex,
      cause of ALF, alanine aminotransferase and total bilirubin levels, prothrombin
      activity and total amount of corticosteroid were analyzed to determine the
      factors associated with the occurrence of opportunistic infection. RESULTS:
      Opportunistic infections occurred in 21.6 % (n = 11) of ALF patients. Thirty-five
      patients underwent systemic corticosteroid therapy, and 31.4 % of those patients
      showed opportunistic infections. Cytomegalovirus (n = 9, 81.8 %) and Pneumocystis
      jiroveci (n = 6, 54.5 %) were the microorganisms frequently suspected as the
      causes of opportunistic infection. In 7 (63.6 %) of the 11 cases of opportunistic
      infection, 2 or more species of microorganism were detected. Seven patients (63.6
      %) with opportunistic infection were cured by treatment. Cox regression analysis
      for the patients who underwent systemic corticosteroid therapy steroid treatment
      revealed that age over 52 years (compared to younger patients: odds ratio = 9.62,
      95 % confidence interval = 1.22-76.9) was only the predictive factor for the
      occurrence of opportunistic infection. CONCLUSION: Opportunistic infections are
      not rare in ALF patients, and the appropriate diagnosis and treatment of these
      infections are critical during ALF treatment.

PMID- 26202505
TI  - Value of shear wave velocity measurements for the risk assessment of
      hepatocellular carcinoma development in patients with nonalcoholic fatty liver
      disease : HCC risk assessment by VTTQ.
AB  - PURPOSE: To evaluate the value of measuring shear wave velocity evoked by
      acoustic radiation force impulse (VTTQ) for the risk assessment of hepatocellular
      carcinoma (HCC) development in patients with nonalcoholic fatty liver disease
      (NAFLD). METHODS: VTTQ was measured three times in each of the four liver
      segments in 163 NAFLD patients, including 14 HCC cases; the results were
      statistically evaluated. RESULTS: The VTTQ was 3.04 +/- 0.17 m/s (median +/-
      median absolute deviation) and 1.27 +/- 0.25 m/s in patients with and without
      HCC, respectively, and was significantly higher in HCC cases (p < 0.001). When
      the patients were classified as F0-F4 based on VTTQ cutoff values, VTTQ was
      significantly higher in the left lobe than in the right lobe for F0 (p < 0.0001)
      and for F1 and F2 combined (p < 0.0001), but not significantly higher for F3 and
      F4 combined (p = 0.070). The robust coefficient of variation was significantly
      higher in the left than in the right (p = 0.018) and significantly increased as
      VTTQ increased (p = 0.0002). Multivariate analysis showed that total bilirubin
      concentration {p = 0.014, 38.9 (2.08-727) [odds ratio (95 % confidence
      interval)]} and VTTQ [p = 0.006, 113 (3.91-3245)] were the only independent
      explanatory factors for HCC presence among the seven variables identified by
      univariate analysis. The area under the receiver-operating characteristic curve
      in the differentiation of HCC from non-HCC was 0.943 for VTTQ and was comparable
      to that for other noninvasive markers such as Fib-4 (0.964) or higher than that
      in BARD (0.838). CONCLUSIONS: These results suggest that fibrosis occurs
      heterogeneously throughout the liver and that VTTQ measurements are useful in HCC
      risk evaluation in a NAFLD cohort.

PMID- 26202506
TI  - Clinical significance of increased expression of Nijmegen breakage syndrome gene
      (NBS1) in human primary liver cancer.
AB  - PURPOSE: As a DNA repair-associated gene essential for maintaining genomic
      instability, Nijmegen breakage syndrome gene (NBS1), codes for a protein,
      Nbs1(p95/Nibrin), involved in the processing/repair of DNA double-strand breaks.
      The aim of this study is to investigate the molecular alteration of Nbs1 in human
      primary liver cancer, including HBV-associated hepatocellular carcinoma (HCC) and
      intrahepatic cholangiocarcinoma (ICC). METHODS: The expression levels of Nbs1 in
      110 cases of primary liver cancer, including 85 HCCs and 25 ICCs, were detected
      by immunohistochemistry, real-time RT-PCR and Western blot analysis. The
      percentage of Ki-67 antigen-positive cells and the level of phosphorylated
      histone H2AX (gamma-H2AX) were detected to evaluate the relationship of Nbs1
      expression with proliferation and the degree of DNA damage in HCC cells. RESULTS:
      Increased Nbs1 expression was observed in tumor compared to corresponding
      adjacent non-tumor tissue in 54.6 and 47.3 % of HCC cases detected with frozen
      tissues and paraffin sections. Higher frequency of increased Nbs1 expression was
      shown in poorly differentiated HCCs (p = 0.0265) and in all poorly differentiated
      ICCs, indicating the increased Nbs1 expression is associated with the degree of
      malignancy of HCC cells. Moreover, the percentage of Ki-67-positive cells and the
      level of gamma-H2AX correlate well with increased Nbs1 expression in HCC cases,
      suggesting an activated DNA damage response in proliferating HCC cells with
      increased Nbs1 expression. CONCLUSION: Increased Nbs1 expression might play a
      significant role in liver cancer progression, and the status of Nbs1 expression
      might be helpful for evaluation of the degree of malignancy of primary liver
      cancer.

PMID- 26202507
TI  - Evaluation and comparison of microvessel density using the markers CD34 and CD105
      in regenerative nodules, dysplastic nodules and hepatocellular carcinoma.
AB  - PURPOSE: The progression of hepatocellular carcinoma (HCC) is multifactorial and
      angiogenesis plays a fundamental role, mainly because HCC is a highly
      vascularized tumor. METHODS: In this study, we determined microvessel density
      (MVD) using the immunohistochemical markers, CD34 and CD105 (Endoglin), in 44
      hepatectomy specimens, encompassing 44 malignant nodules (HCC), 44 regenerative
      nodules (RN), and 15 dysplastic nodules (DN). The evaluation included the
      determination of MVD in all nodules. For statistical analysis, a descriptive
      analysis was carried out using measurements of position and dispersion for
      continuous variables; ANOVA was used to compare between groups, considering p <
      0.05 as statistically significant. RESULTS: We observed a significant difference
      when comparing CD34 and CD105 immunoexpression in HCC, DN, and RN. CD105 was
      predominantly expressed in the peripheral regions in HCC, with mean MVD scores of
      6.2 +/- 4.1 and 10.7 +/- 4.4 at the center and periphery of the nodules,
      respectively, with significant differences between groups (p < 0.0001). CD34 had
      higher mean MVD scores than CD105 in HCC, with a more uniform positivity pattern.
      CD105 immunoexpression in DN exhibited a pattern similar to HCC. However, in RN,
      CD105 exhibited a higher MVD score in the central portion of the nodules. CD105
      was expressed in a subset of newly formed microvessels in HCC and demonstrated an
      elevated mean MVD in cirrhotic or regenerative nodules. CONCLUSIONS: MVD
      determined by CD34 and CD105 expression may be used as an additional parameter to
      distinguish benign from malignant liver nodules.

PMID- 26202508
TI  - Increased cancer risk in a large population-based cohort of patients with primary
      biliary cirrhosis: follow-up for up to 36 years.
AB  - BACKGROUND AND AIMS: The natural history of primary biliary cirrhosis (PBC) has
      so far mainly been studied in tertiary referral centres. The aim of the present
      investigation was to describe the natural history of PBC in a large population
      based cohort in order to identify risk factors for development of malignancies
      and disease progression. METHODS: Four independent hospital databases were
      searched in 44 hospitals in a geographically defined area, after which all
      medical records were evaluated on site. In addition, PBC registries in the three
      liver transplant centers were checked for missed referrals from the area of
      interest. RESULTS: In total, 992 cases fulfilled the inclusion criteria. The
      median follow-up was 73 months (range 0-434). Mortality was similar to the age-
      and gender matched population (SMR 1.1; 95 % CI 0.9-1.4). Male gender, smoking,
      and elevated bilirubin, decreased albumin, and elevated AST at time of diagnosis,
      were associated with an increased risk for the combined end point PBC-related
      death or liver transplantation. In total, 133 (13 %) patients developed one or
      more malignancies (SIR 1.5; 95 % CI 1.1-1.9). There was a ninefold increased risk
      of developing hepatobiliary malignancies (SIR 9.4; 95 % CI 3.04-21.8), a fivefold
      increased risk of developing urinary bladder cancer (SIR 5.0; 95 % CI 1.6-11.6),
      and a 1.8-fold increased risk of developing breast cancer (SIR 1.8; 95 % CI 1.08
      2.81). CONCLUSION: PBC is associated with an increased risk of hepatobiliary,
      bladder and breast cancer. Still, survival-under treatment with ursodeoxycholic
      acid (UDCA)-was comparable to the general population in this population-based
      study.

PMID- 26202509
TI  - S-Adenosylmethionine attenuates lipopolysaccharide-induced liver injury by
      downregulating the Toll-like receptor 4 signal in Kupffer cells.
AB  - PURPOSE: S-Adenosylmethionine (SAM) is beneficial for lipopolysaccharide (LPS)
      induced liver injury, but its molecular basis is not fully understood. The
      present study was carried out to investigate the effects of SAM on LPS signal
      transduction and its possible mechanism. METHODS: An animal model of LPS-induced
      liver injury was established by intraperitoneally injecting mice with 10 mg/kg
      LPS pretreatment with or without SAM (170 MUmol/kg body weight). Toll-like
      receptor 4 (TLR4) protein expression in liver tissues and the tumor necrosis
      factor alpha (TNF-alpha) secretion level in serum were detected by
      immunohistochemistry and enzyme-linked immunosorbent assay, respectively. Then,
      Kupffer cells (KCs) were isolated and challenged with LPS, with or without SAM
      pretreatment (1,000 MUM), and the expressions of TLR4 and myeloid differentiation
      primary response protein (MYD88) were assayed at the mRNA and protein levels. The
      activities of nuclear factor-kappa B (NF-kappaB) and p38 mitogen-activated
      protein kinase (MAPK) were also analyzed using Western blotting. RESULTS: SAM
      significantly improved the survival rate of endotoxemic mice (p < 0.05) and
      decreased TNF-alpha levels in serum (p < 0.05). Simultaneously, SAM also
      attenuated LPS-induced liver injury and expression of TLR4 and MYD88 in the
      hepatic sinusoid. Moreover, TLR4 and MYD88 gene and protein expressions were
      downregulated by SAM pretreatment in LPS-stimulated KCs. Finally, SAM did not
      affect NF-kappaB-p65 translocation into the nucleus (p > 0.05), but significantly
      inhibited p38 MAPK activation (p < 0.05). CONCLUSIONS: SAM attenuated liver
      injury and improved the survival rate in endotoxemic mice by decreasing the TNF
      alpha expression. The downregulative effect of SAM on TNF-alpha was mediated by
      suppressing activation of the TLR4/MAPK signaling pathway.

PMID- 26202510
TI  - Strategies to treat interferon-induced graft dysfunction after living donor liver
      transplantation for hepatitis C.
AB  - PURPOSE: Interferon-induced graft dysfunction (IGD) is a poorly defined,
      unrecognized, but potentially serious condition for patients receiving antiviral
      drugs after liver transplantation for hepatitis C. METHODS: We evaluated the
      characteristics of 80 patients who received pegylated interferon-based antiviral
      treatment for hepatitis C after living donor liver transplantation (LDLT).
      RESULTS: Eight patients experienced IGD either during (n = 6) or after completing
      (n = 2) antiviral treatment. Pathological diagnosis included acute cellular
      rejection (ACR, n = 1), plasma cell hepatitis (PCH, n = 2), PCH plus ACR (n = 3),
      and chronic rejection (CR, n = 2). One patient with CR initially presented with
      PCH plus ACR and the other presented with ACR; both had apparent cholestasis. The
      six patients with ACR or PCH without cholestasis were successfully treated by
      discontinuing antiviral treatment and increasing immunosuppression, including
      steroids. By contrast, both of the patients with CR and cholestasis experienced
      graft loss, despite aggressive treatment. Univariate analysis showed that
      pegylated interferon-alpha2a-based treatment (75 vs. 26.4 %, p < 0.01) was the
      only significant factor for IGD, and was associated with decreased 5-year graft
      survival (93.4 vs. 71.4 %, p = 0.04). CONCLUSIONS: IGD is a serious condition
      during or even after antiviral treatment for hepatitis C after LDLT. Early
      recognition, diagnosis, discontinuation of interferon, and introduction of
      steroid-based treatment may help to save the graft.

PMID- 26202511
TI  - The reduction rate of serum C3 following liver transplantation is an effective
      predictor of non-anastomotic strictures.
AB  - PURPOSE: Non-anastomotic biliary strictures (NAS) are considered to be the
      thorniest complications following liver transplantation (LT). How to predict and
      adopt specific measures early to minimize the occurrence of it remains unclear.
      In this study, we aimed to find the relationship between the change rate of serum
      complement level and NAS. METHODS: In a series of 232 adult patients who
      underwent their first LT, serum C3 and C4 concentrations at predetermined time
      points were collected. The correlation between the change rate of serum
      complement level following LT and the clinical outcome of NAS was retrospectively
      studied. RESULTS: The reduction rate of serum C3 at the 1st day following LT in
      NAS patients was significantly different from that in non-NAS patients (p <
      0.01). Receiver operating characteristic curve analysis demonstrated that the
      reduction rate of serum C3 is an effective predictor of NAS with an area under
      curve of 82.5 % (95 % CI 77.0-87.2 %). The reduction rate of C3 in the severe NAS
      group was significantly higher than that in the mild NAS group and the non-NAS
      group (p < 0.01). CONCLUSIONS: Complement activation plays important roles on the
      progression of NAS. The reduction rate of serum C3 is an effective predictor of
      NAS.

PMID- 26202512
TI  - Synaptotagmins interact with APP and promote Abeta generation.
AB  - BACKGROUND: Accumulation of the beta-amyloid peptide (Abeta) is a major
      pathological hallmark of Alzheimer's disease (AD). Recent studies have shown that
      synaptic Abeta toxicity may directly impair synaptic function. However, proteins
      regulating Abeta generation at the synapse have not been characterized. Here, we
      sought to identify synaptic proteins that interact with the extracellular domain
      of APP and regulate Abeta generation. RESULTS: Affinity purification-coupled mass
      spectrometry identified members of the Synaptotagmin (Syt) family as novel
      interacting proteins with the APP ectodomain in mouse brains. Syt-1, -2 and -9
      interacted with APP in cells and in mouse brains in vivo. Using a GST pull-down
      approach, we have further demonstrated that the Syt interaction site lies in the
      108 amino acids linker region between the E1 and KPI domains of APP. Stable
      overexpression of Syt-1 or Syt-9 with APP in CHO and rat pheochromocytoma cells
      (PC12) significantly increased APP-CTF and sAPP levels, with a 2 to 3 fold
      increase in secreted Abeta levels in PC12 cells. Moreover, using a stable
      knockdown approach to reduce the expression of endogenous Syt-1 in PC12 cells, we
      have observed a ~ 50% reduction in secreted Abeta generation. APP processing also
      decreased in these cells, shown by lower CTF levels. Lentiviral-mediated knock
      down of endogenous Syt-1 in mouse primary neurons also led to a significant
      reduction in both Abeta40 and Abeta42 generation. As secreted sAPPbeta levels
      were significantly reduced in PC12 cells lacking Syt-1 expression, our results
      suggest that Syt-1 regulates Abeta generation by modulating BACE1-mediated
      cleavage of APP. CONCLUSION: Altogether, our data identify the synaptic vesicle
      proteins Syt-1 and 9 as novel APP-interacting proteins that promote Abeta
      generation and thus may play an important role in the pathogenesis of AD.

PMID- 26202513
TI  - Human papillomavirus infection and cervical dysplasia in female sex workers in
      Northeast China: an observational study.
AB  - BACKGROUND: Women having multiple sex partners are reportedly at an increased
      risk of HPV infection. However, the prevalence and risk factors of HPV infection
      in female sex workers (FSWs) vary considerably across racial/ethnic,
      socioeconomic, and geographic groups. This study aimed to determine the
      prevalence and risk factors of HPV infection in FSWs in Northeast China. METHODS:
      A total of 309 FSWs identified and approached through a local police office and
      1000 healthy subjects from a single factor undergoing annual gynecological
      examinations in Shenyang were recruited. A liquid-based ThinPrep Pap test and the
      Hybrid Capture II-based high-risk HPV DNA test, with or without a colposcopic
      examination, were performed on both FSWs and control subjects. Data on HPV
      infection and histological and cytological lesions of the cervix were obtained
      and analyzed. A questionnaire survey was administered to all 309 FSWs with their
      socio-demographic and behavioral information collected. The association of
      various socio-demographic and behavioral variables with HPV infection was
      assessed. RESULTS: HPV was significantly more prevalent in FSWs (61.90%) than in
      healthy control subjects (21.00%) (P < 0.01), so were cervical lesions (P <
      0.01). HPV prevalence in our sample of FSWs fell in the upper range of reported
      values in FSWs across different countries, and was similar to that for FSWs in
      the southeast Chinese city of Huzhou but higher than that for FSWs in southwest
      China, Guangxi, as compared with data from other studies within China. HPV
      infection in FSWs was significantly associated with the age at first sexual
      intercourse (OR 0.699, 95% CI 0.492-0.992) and post-menopause (OR 2.928, 95% CI
      1.099-7.800) (P < 0.05). CONCLUSIONS: FSWs are at a substantially high risk of
      HPV infection and cervical dysplasia development as compared with healthy control
      subjects in Shenyang, China. Age of first sexual intercourse and post-menopause
      are two independent risk factors for HPV infection in this special group of
      population. Intensified and coordinated efforts from government, public health
      sector, communities and families are needed to reduce the risk of HPV infection
      in this specific group of population.

PMID- 26202514
TI  - All-cause mortality and use of antithrombotics within 90 days of discharge in
      acutely ill medical patients.
AB  - Conflicting evidence exists regarding predictors of and antithrombotic benefit on
      mortality in hospitalised acutely-ill medical patients. We compared mortality
      risk within 90 days post-discharge among medically ill patients who did and did
      not receive antithrombotics. This retrospective claims analysis included patients
      >= 40 years with nonsurgical hospitalisation >= 2 days between 2005 and 2009
      using the HealthCore Integrated Research Database. Antithrombotic use (i.e.
      anticoagulants and antiplatelets) post-discharge was captured from pharmacy
      claims. All-cause mortality was determined from Social Security Death Index;
      cause of death was identified from National Death Index database. Kaplan-Meier
      survival curves were generated and hazard ratios (HR) for mortality risk were
      estimated using Cox proportional hazards models. Patients prescribed
      anticoagulants or antiplatelets post-discharge had lower risk of short-term
      mortality. For the anticoagulant model, the most significant predictors of
      mortality were malignant/benign neoplasms (hazard ratio [HR] 1.6, 95% confidence
      interval [CI] 1.5-1.7), liver disease (HR 1.6, 95% CI 1.5-1.7), anticoagulant
      omission (HR 1.6, 95% CI 1.4-1.8), gastrointestinal or respiratory tract
      intubations (HR 1.5, 95% CI 1.3-1.7), and blood dyscrasias (HR 1.4, 95% CI 1.4
      1.5). For the antiplatelet model, the most significant predictors of mortality
      were antiplatelet omission (HR 3.7, 95% CI 3.3-4.1), liver disease (HR 1.6, 95%
      CI 1.4-1.7), malignant/benign neoplasms (HR 1.6, 95% CI 1.5-1.6),
      gastrointestinal or respiratory tract intubations (HR 1.5, 95% CI 1.3-1.7), and
      blood dyscrasias (HR 1.4, 95% CI 1.4-1.5). These mortality risk factors may guide
      future studies assessing potential benefits of antithrombotics in specific
      subsets of patients.

PMID- 26202515
TI  - Development and validation of a feline abdominal palpation model and scoring
      rubric.
AB  - Simulation in veterinary education enables clinical skills practice without
      animal use. A feline abdominal palpation model was created that allows practice
      in this fractious species. This study assessed the model and rubric using a
      validation framework of content evidence, internal structure and relationship
      with level of training. Content Evidence: Veterinarians accepted this model as a
      helpful training tool for students (median=4 on five-point Likert scale).
      Internal Structure Evidence: G-coefficients were low for first- and second-year
      students (0.28 and 0.23), but were acceptable for veterinarians (0.61). Internal
      consistency values (0.24, 0.42 and 0.67) followed a similar pattern. Thus, scores
      were more reliable for veterinarians than for the students. Evidence of
      Relationship with Level of Training: Although level of training impacted
      reliability, its effect on performance scores was inconsistent. Analysis of
      variance (ANOVA) identified no differences among the groups of students and
      veterinarians. However, effect size between first- and third-year students was
      medium to large (0.62). Effect sizes between the veterinarians and student groups
      were small. Although the model and rubric appeared valid for experts,
      modifications would be necessary to generate reliable scores for students. These
      results allow greater understanding of the needs of students utilising a low
      fidelity model. 

PMID- 26202516
TI  - Enhanced Specificity and Drug Delivery in Tumors by cRGD-Anchoring
      Thermosensitive Liposomes.
AB  - PURPOSE: To develop RGD-targeted thermosensitive liposomes with increased tumor
      retention, improving drug release efficiency upon mild hyperthermia (HT) in both
      tumor and angiogenic endothelial cells. METHODS: Standard termosensitive
      liposomes (TSL) and TSL containing a cyclic Arg-Gly-Asp (cRGD) pentapeptide with
      the sequence Arg-Cys-D-Phe-Asp-Gly (RGDf[N-Met]C) were synthetized, loaded with
      Dox and characterized. Temperature- and time-dependent drug release profiles were
      assessed by fluorometry. Intracellular Dox delivery was studied by flow cytometry
      and confocal microscopy. Cytotoxic effect of TSL and RGD-TSL was studied on
      B16Bl6 melanoma, B16F10 melanoma and HUVEC. Intravital microscopy was performed
      on B16Bl6 tumors implanted in dorsal-skin fold window-bearing mice.
      Pharmacokinetic and biodistribution of Dox-TSL and Dox-RGD-TSL were followed in
      B16Bl6 tumor bearing mice upon normothermia or initial hyperthermia conditions.
      RESULTS: DLS and cryo-TEM revealed particle homogeneity and size of around 85 nm.
      Doxorubicin loading efficiency was >95%as assessed by spectrofluorometry. Flow
      cytometry and confocal microscopy showed a specific uptake of RGD-TSL by melanoma
      and endothelial cells when compared to TSL and an increased doxorubicin delivery.
      High resolution intravital microscopy demonstrated specific accumulation of RGD
      TSL to the tumor vasculature. Moreover, application of hyperthermia resulted in
      massive drug release from RGD-TSL. Biodistribution studies showed that initial
      hyperthermia increases Dox uptake in tumors from TSL and RGD-TSL. CONCLUSION: RGD
      TSL have potency to increase drug efficacy due to higher uptake by tumor and
      angiogenic endothelial cells in combination with heat-triggered drug release.

PMID- 26202517
TI  - The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients
      Before and One Year After Bariatric Surgery.
AB  - PURPOSE: Bariatric surgery is nowadays commonly applied as treatment for morbid
      obesity (BMI > 40 kg/m(2)). As information about the effects of this procedure on
      a drug's pharmacokinetics is limited, we aimed to evaluate the pharmacokinetics
      of CYP3A probe substrate midazolam after oral and intravenous administration in a
      cohort of morbidly obese patients that was studied before and 1 year post
      bariatric surgery. METHODS: Twenty morbidly obese patients (aged 26-58 years)
      undergoing bariatric surgery participated in the study of which 18 patients
      returned 1 year after surgery. At both occasions, patients received 7.5 mg oral
      and 5 mg intravenous midazolam separated by 160 +/- 48 min. Per patient and
      occasion, a mean of 22 blood samples were collected. Midazolam concentrations
      were analyzed using population pharmacokinetic modeling. RESULTS: One year after
      bariatric surgery, systemic clearance of midazolam was higher [0.65 (7%) versus
      0.39 (11%) L/min, mean +/- RSE (P < 0.01), respectively] and mean oral transit
      time (MTT) was faster [23 (20%) versus 51 (15%) minutes (P < 0.01)], while oral
      bioavailability was unchanged (0.54 (9%)). Central and peripheral volumes of
      distribution were overall lower (P < 0.05). CONCLUSIONS: In this cohort study in
      morbidly obese patients, systemic clearance was 1.7 times higher 1 year after
      bariatric surgery, which may potentially result from an increase in hepatic CYP3A
      activity per unit of liver weight. Although MTT was found to be faster, oral
      bioavailability remained unchanged, which considering the increased systemic
      clearance implies an increase in the fraction escaping intestinal first pass
      metabolism.

PMID- 26202518
TI  - Solid Phase Extraction as an Innovative Separation Method for Measuring Free and
      Entrapped Drug in Lipid Nanoparticles.
AB  - PURPOSE: Contrary to physical characterization techniques for nanopharmaceuticals
      (shape, size and zeta-potential), the techniques to quantify the free and the
      entrapped drug remain very few and difficult to transpose in routine analytical
      laboratories. The application of Solid Phase Extraction (SPE) technique was
      investigated to overcome this challenge. METHODS: The separation of free and
      entrapped drug by SPE was quantitatively validated by High Performance Liquid
      Chromatography. The developed protocol was implemented to characterize
      cyclosporine A-loaded 120 nm-sized lipid nanoparticles (LNPs, Lipidot(r))
      dispersed in aqueous buffer. The colloidal stability was assessed by Dynamic
      Light Scattering (DLS). RESULTS: Validation experiments demonstrated suitable
      linearity, repeatability, accuracy and specificity to quantify residual free,
      entrapped and total drug. For the investigated LNPs, the method revealed a very
      limited shelflife of the formulation when stored in an aqueous buffer at 5
      degrees C and even more at elevated temperature. Nevertheless, the DLS
      measurements confirmed the stability of nanoparticles during SPE in a suitable
      concentration range. CONCLUSIONS: SPE, when successfully validated, represents a
      valuable tool for drug development and quality control purposes of lipid-based
      nanopharmaceuticals in an industrial environment.

PMID- 26202519
TI  - Capillary electrophoresis reveals polyamine metabolism modulation in Leishmania
      (Leishmania) amazonensis wild-type and arginase-knockout mutants under arginine
      starvation.
AB  - l-Arginine is an essential amino acid in Leishmania (Leishmania) amazonensis
      metabolism. A key enzyme for parasite l-arginine metabolism is arginase (ARG)
      that uses arginine to produce urea and ornithine, a precursor of polyamine
      pathway guaranteeing parasite replication in both insect and mammal hosts. There
      is an alternative pathway to produce ornithine via l-proline and glutamate, but
      this mechanism is not described in Leishmania. In the mammal host, two enzymes
      can use l-arginine as substrate, the host ARG and the induced nitric oxide
      synthase that produces nitric oxide. The competition between induced nitric oxide
      synthase and both parasite and host ARG can favor the success of the infection or
      its control. Here, we established the metabolomics profile of the polyamine
      pathway of wild type (WT) L. (L.) amazonensis, submitted or not to l-arginine
      starvation, and compared to the ARG-knockout mutant (arg- ). Our results
      indicated that arginine starvation induces a decrease in arginine, ornithine, and
      putrescine, but we could not detect the significative level changes of
      spermidine, spermine, or agmatine. However, the absence of ARG on the arg-
      induced an increase of arginine and citrulline levels, but decreased the levels
      of ornithine and putrescine. Similarly to the WT arginine-starved parasites, the
      arg- parasites presented lower levels of proline when compared to the WT ones.
      This could be indicative of an alternative pathway to surpass the enzyme or its
      substrate absence.

PMID- 26202520
TI  - Isolation of coagulase-positive staphylococci from bitches' colostrum and milk
      and genetic typing of methicillin-resistant Staphylococcus pseudintermedius
      strains.
AB  - BACKGROUND: Among the coagulase-positive, potentially pathogenic staphylococci,
      Staphylococcus pseudintermedius has been frequently isolated from bitches' milk.
      This organism colonizes the mammary gland or causes infection, while S. aureus
      has been only occasionally reported. The objective of this study was to
      investigate the occurrence and persistence of coagulase-positive staphylococci in
      the colostrum and milk of postpartum bitches, either treated or untreated with
      antimicrobials, and to assess the incidence, antibiotic resistance profile and
      genetic type of the methicillin-resistant strains. On postpartum D1, D7 and D15,
      drops of secretion were collected from the mammary glands of 27 postpartum
      bitches, nine of which were treated with antimicrobials. Coagulase-positive
      staphylococci were identified, antimicrobial susceptibility and the presence of
      mecA were tested and the genetic profile of methicillin-resistant strains was
      assessed. RESULTS: Staphylococcus pseudintermedius was the only coagulase
      positive staphylococcus isolated, and its presence was detected in 21 out of 27
      bitches and in 66 out of 145 swabs. In a single bitch, it caused puerperal
      mastitis. In untreated bitches, the frequency of isolation was lower in colostrum
      than in milk. All of the isolates except one were resistant to at least three
      antimicrobial classes, while 14 out of 66 S. pseudintermedius strains were
      methicillin-resistant mecA positive (MRSP) and were isolated from eight bitches
      housed in the same breeding kennel. A significant association was found between
      antimicrobial treatment and the presence of MRSP. Six of the 12 typed isolates
      belonged to spa-type t02 carrying SCCmec II/III, and another six were non
      typeable with spa carrying SCCmec IV. The t02-SCCmec II/III isolates were
      sequence type (ST) 71; four NT-SCCmec IV isolates were ST258 and two were ST369.
      PFGE showed that isolates from the same dog had identical band patterns, while
      isolates from different dogs had unique band patterns. MRSP strains showed
      multidrug resistance profiles. CONCLUSIONS: Our results confirm that S.
      pseudintermedius is the most frequently isolated coagulase-positive
      staphylococcus from bitches' milk. The isolation of several different strains of
      MRSP with different genetic characteristics in the same kennel and the fact that
      two of the strains belonged to a sequence type (ST) described for the first time
      are noteworthy findings.

PMID- 26202521
TI  - Adolescent-onset of cocaine use is associated with heightened stress-induced
      reinstatement of cocaine seeking.
AB  - Adolescent rats take cocaine more readily than adults, are more sensitive to
      lower doses of the drug and work harder for it. It remains unknown if adolescent
      onset of cocaine use has long-term consequences on adult relapse liability.
      Therefore, we tested if self-administering cocaine during adolescence impacts
      subsequent stress-induced reinstatement to cocaine seeking and taking, after a
      prolonged drug-free period. Adolescent (~P42) or adult (P88) rats self
      administered cocaine (0.6 or 1.2 mg/kg/infusion) for 7 or 10 days. Then, they
      underwent a prolonged drug-free period (21-40 days), after which they were tested
      for reinstatement of cocaine-seeking (i.e. responding in the absence of cocaine)
      induced by the stress hormone corticosterone, the pharmacological stressor
      yohimbine or electric footshock. Studies employed either single extinction
      session (within-session extinction/reinstatement) or repeated extinction prior to
      reinstatement (between-session extinction/reinstatement). Finally, in a separate
      set of experiments, rats underwent a prolonged drug-free period (~40 days) and
      were then allowed to self-administer cocaine again, using progressive-ratio
      procedures that appraise the reinforcing efficacy of cocaine. Rats with
      adolescent-onset of cocaine use showed greater stress-induced reinstatement of
      cocaine seeking than rats with adult-onset of cocaine use. This was observed
      across conditions, providing external validity to these results. Groups did not
      differ on drug taking in progressive-ratio tests. Our studies indicate that
      experiencing cocaine during adolescence renders subjects particularly responsive
      to the subsequent effects of stress on drug seeking. This heightened propensity
      for reinstatement puts adolescent-onset drug users at heightened risk for
      relapse. 

PMID- 26202525
TI  - A theoretical study of potentially observable chirality-sensitive NMR effects in
      molecules.
AB  - Two recently predicted nuclear magnetic resonance effects, the chirality-induced
      rotating electric polarization and the oscillating magnetization, are examined
      for several experimentally available chiral molecules. We discuss in detail the
      requirements for experimental detection of chirality-sensitive NMR effects of the
      studied molecules. These requirements are related to two parameters: the
      shielding polarizability and the antisymmetric part of the nuclear magnetic
      shielding tensor. The dominant second contribution has been computed for small
      molecules at the coupled cluster and density functional theory levels. It was
      found that DFT calculations using the KT2 functional and the aug-cc-pCVTZ basis
      set adequately reproduce the CCSD(T) values obtained with the same basis set. The
      largest values of parameters, thus most promising from the experimental point of
      view, were obtained for the fluorine nuclei in 1,3-difluorocyclopropene and 1,3
      diphenyl-2-fluoro-3-trifluoromethylcyclopropene. 

PMID- 26202523
TI  - Unfolded protein response is activated in Lewy body dementias.
AB  - AIM: The unfolded protein response (UPR) is a pro-survival defence mechanism
      induced during periods of endoplasmic reticulum stress, and it has recently
      emerged as an attractive therapeutic target across a number of neurodegenerative
      conditions, but has not yet been studied in synuclein disorders. METHODS: The
      level of a key mediator of the UPR pathway, glucose-regulated protein 78 (GRP78),
      also known as binding immunoglobulin protein (BiP), was measured in post mortem
      brain tissue of patients with dementia with Lewy bodies (DLB) and Parkinson's
      disease dementia (PDD) in comparison with Alzheimer's disease (AD) and age
      matched controls using Western blot. The UPR activation was further confirmed by
      immunohistochemical detection of GRP78/BiP and phosphorylated protein kinase RNA
      like endoplasmic reticulum (ER) kinase (p-PERK). RESULTS: GRP78/BiP was increased
      to a greater extent in DLB and PDD patients compared with AD and control subjects
      in cingulate gyrus and parietal cortex. However, there were no changes in the
      prefrontal and temporal cortices. There was a significant positive correlation
      between GRP78/BiP level and alpha-synuclein pathology in the cingulate gyrus,
      while AD-type pathology showed an inverse correlation relationship in the
      parietal cortex. CONCLUSION: Overall, these results give emphasis to the role of
      UPR in Lewy body dementias, and suggest that Lewy body degeneration, in
      combination with AD-type pathologies, is associated with increased UPR activation
      to a greater extent than AD alone, possibly as a consequence of the increasing
      load of ER proteins. This work also highlights a novel opportunity to explore the
      UPR as a therapeutic target in synuclein diseases.

PMID- 26202522
TI  - Mining Missing Membrane Proteins by High-pH Reverse-Phase StageTip Fractionation
      and Multiple Reaction Monitoring Mass Spectrometry.
AB  - Despite significant efforts in the past decade toward complete mapping of the
      human proteome, 3564 proteins (neXtProt, 09-2014) are still "missing proteins".
      Over one-third of these missing proteins are annotated as membrane proteins,
      owing to their relatively challenging accessibility with standard shotgun
      proteomics. Using nonsmall cell lung cancer (NSCLC) as a model study, we aim to
      mine missing proteins from disease-associated membrane proteome, which may be
      still largely under-represented. To increase identification coverage, we employed
      Hp-RP StageTip prefractionation of membrane-enriched samples from 11 NSCLC cell
      lines. Analysis of membrane samples from 20 pairs of tumor and adjacent normal
      lung tissue was incorporated to include physiologically expressed membrane
      proteins. Using multiple search engines (X!Tandem, Comet, and Mascot) and
      stringent evaluation of FDR (MAYU and PeptideShaker), we identified 7702 proteins
      (66% membrane proteins) and 178 missing proteins (74 membrane proteins) with PSM
      , peptide-, and protein-level FDR of 1%. Through multiple reaction monitoring
      using synthetic peptides, we provided additional evidence of eight missing
      proteins including seven with transmembrane helix domains. This study
      demonstrates that mining missing proteins focused on cancer membrane subproteome
      can greatly contribute to map the whole human proteome. All data were deposited
      into ProteomeXchange with the identifier PXD002224. 

PMID- 26202526
TI  - The role of placental MHC class I expression in immune-assisted separation of the
      fetal membranes in cattle.
AB  - The bovine fetus, like that of other species, is a semi-allograft and the
      regulation of materno-fetal alloimmunity is critical to prevent its immunological
      rejection. In cattle, a materno-fetal alloimmune response may be beneficial at
      parturition. It is hypothesized that upregulation of major histocompatibility
      complex (MHC) class I on the fetal membranes toward the end of gestation induces
      a maternal alloimmune response that activates innate immune effector mechanisms,
      aiding in the loss of the adherence between the fetal membranes and the uterus.
      Loss of fetal-maternal adherence is pivotal for the timely expulsion of the fetal
      membranes and the absence (or reduction) of the maternal immune response may lead
      to retained fetal membranes, a common reproductive disorder of cattle. Currently,
      there is no effective treatment for retained fetal membranes and a better
      understanding of materno-fetal alloimmune-assisted separation of the fetal
      membranes may lead to novel targets for the treatment of retained fetal
      membranes. In this review, the regulation of materno-fetal alloimmunity during
      pregnancy in cattle, with a focus on placental MHC class I expression, and the
      importance of maternal alloimmunity for the timely separation of the fetal
      membranes, are discussed. 

PMID- 26202527
TI  - Prevalence and determinants of the early repolarisation pattern in a group of
      young high endurance rowers.
AB  - BACKGROUND: The prevalence and significance of the early repolarisation (ER)
      pattern in the general population has raised a number of questions. Even less
      data are available on athletes. AIM: To determine the prevalence and determinants
      of ER in a group of young high endurance athletes. METHODS: We studied 117 rowers
      (46% women, mean age 17.5 +/- 1.5 years, mean training duration 4.3 +/- 1.8
      years). On 12-lead electrocardiogram (ECG), we evaluated inferolateral leads for
      the presence of the ER pattern, defined as at least 0.1 mV elevation of the QRS
      ST junction (J point) from the baseline in at least two leads. All subjects
      underwent detailed echocardiographic study, cardiopulmonary exercise test with
      evaluation of VO2max (mean 57.1 +/- 8.4 mL/kg/min), and evaluation of complete
      blood count and biometric parameters (fat tissue, body mass index, body surface
      area). RESULTS: We identified 35 subjects with ER in the inferior and/or lateral
      leads. The phenomenon was more frequent in males (n = 25, 21.36% of the overall
      study population) than in females (n = 10, 8.54%, p = 0.01). The training
      duration in both groups (with or without ER) was similar (4.4 +/- 1.5 vs. 4.3 +/-
      1.8 years, p > 0.05). Athletes with the ER pattern had significantly higher
      VO2max (58.8 +/- 7.8 vs. 55.3 +/- 8.2 mL/kg/min, p = 0.03), lower resting heart
      rate (58.7 +/- 11.3 vs. 65.4 +/- 11.9 bpm, p < 0.01), higher haemoglobin level
      (15.2 +/- 0.8 vs. 14.6 +/- 1.2 g/dL, p < 0.01), higher red blood cell count (5.31
      +/- 0.3 vs. 4.98 +/- 0.4 million/MUL, p = 0.04), and lower fat tissue mass (12.1
      +/- 4.4 vs. 14.9 +/- 6.0 kg, p < 0.01). Compared with the others, the ER group
      was characterised by a higher left atrial area index (12.2 +/- 1.3 vs. 11.5 +/-
      1.6 cm2/m2, p = 0.01), right atrial area index (9.9 +/- 1.3 vs. 9.0 +/- 1.4
      cm2/m2, p < 0.01), and right ventricular basal diameter index (2.0 +/- 0.2 vs.
      1.9 +/- 0.2 cm/m2, p = 0.04). We found no significant differences in any other
      cardiac size and function parameters. CONCLUSIONS: ER pattern in the inferior
      and/or lateral leads is a frequent finding in the population of young high
      endurance rowers. The presence of ER pattern is associated with gender and a
      number of parameters reflecting the general level of fitness and may be
      considered an electrophysiological sign of the athlete's heart. The significance
      of these alterations should be evaluated in prospective follow-up studies.

PMID- 26202528
TI  - Bicuspid aortic valve morphology and its association with aortic diameter: an
      echocardiographic study.
AB  - BACKGROUND: Bicuspid aortic valve (BAV) is strongly associated with aortopathy.
      Previous studies have suggested that various types of bicuspid aortic valve
      morphology may differently affect the aortic dilatation. AIM: To evaluate the
      impact of BAV cusp fusion morphology (type I - right-left coronary cusp fusion;
      type II - right-noncoronary cusp fusion) on the diameters of the aorta. METHODS:
      BAV morphology was evaluated retrospectively in a group of 67 consecutive
      patients with BAV. The control group comprised 1000 randomly selected patients
      with normal tricuspid aortic valve. Aortic dimensions and other echocardiographic
      parameters were obtained from the echocardiography database of our department.
      The diameters of aorta in both BAV sub-types were evaluated at the level of:
      annulus, the sinus of Valsalva, the sinotubular junction, and the ascending aorta
      and at the level of the ascending aorta in the control group. RESULTS: Patients
      with BAV were mainly male (78%), with a mean age of 55.3 +/- 16.7 years. The
      dominant morphology of BAV in the study group was type I (n = 46; 69%). It was
      associated with increased aortic dimension in comparison to type II BAVs at the
      level of the sinuses of Valsalva (38.4 +/- 5.2 vs. 34.0 +/- 4.6 mm, p = 0.002),
      the sinotubular junction (33.1 +/- 5.8 vs. 29.6 +/- 5.0 mm, p = 0.035), and the
      ascending aorta (41.6 +/- 7.1 vs. 36.6 +/- 6.1 mm, p = 0.006). Indexed aortic
      diameter was also increased in type I BAV at the level of sinuses of Valsalva
      (19.6 +/- 2.7 vs. 18.1 +/- 1.6 mm/m2, p = 0.008) and the ascending aorta (21.3 +/
      3.4 vs. 19.3 +/- 3.4 mm/m2, p = 0.048). The dimensions of the ascending aorta
      exceeding the upper normal range limit based on control-group measurements (44.3
      mm) were observed more frequently in type I than in type II (33% vs. 10%, p =
      0.044). Aortic regurgitation (moderate or severe) occurred in similar percentages
      of both BAV subtypes (type I: 37% vs. type II: 33%, p = 0.774). There were also
      no significant differences in aortic valve area (2.2 +/- 1.1 vs. 2.0 +/- 1.4 cm2,
      p = 0.163), indexed aortic valve area (1.1 +/- 0.6 vs. 1.0 +/- 0.6, p = 0.337),
      peak transvalvular gradient (35.3 +/- 20.5 vs. 39.1 +/- 28.9 mm Hg, p = 0.862),
      and mean gradient (18.6 +/- 12.3 vs. 22.7 +/- 18.2 mm Hg, p = 0.571) and left
      ventricular ejection fraction (51.8 +/- 11.6 vs. 51.8 +/- 12.2%, p = 0.978)
      between type I and type II BAV groups. CONCLUSIONS: Type I BAV cusp fusion
      morphology is more commonly associated with dilatation of the aorta than type II,
      especially at the level of the sinus of Valsalva and the ascending aorta.

PMID- 26202529
TI  - Coronary computed tomography angiography for the assessment of SYNTAX score.
AB  - BACKGROUND: Coronary computed tomography angiography (CCTA) is applied in a
      growing number of clinical indications. This imaging modality is often regarded
      as a surrogate of invasive coronary angiography (ICA). In this paper we evaluate
      the applicability of CCTA alone in the assessment of the SYNTAX score. AIM: To
      evaluate the feasibility of calculating the SYNTAX score (SXScore) using CCTA
      alone instead of ICA. METHODS: Ninety consecutive patients with multivessel or
      left main (LM) coronary artery disease diagnosed with ICA, in whom prior CCTA
      scan was available, were included in a post-hoc analysis. First, the SXScore was
      calculated twice in ten-week intervals by two experienced observers using ICA for
      each patient. Then the SXScore was calculated twice using CCTA following the same
      regimen for each patient. Weighted kappa statistic was used to assess the intra
      modality and inter-modality reproducibility of the SXScore. RESULTS: Ninety
      patients, aged 63.8 +/- 8.9 years, 60% male, 64.4% with two-vessel disease, and
      35.6% with three-vessel or LM disease met the inclusion criteria. 287 lesions
      were identified by ICA and 280 by CCTA (p = 0.56). Median total SXScore was 11.5
      (10.2-14.0) as calculated by ICA and 16.0 (14.3-19.4) by CCTA (p < 0.001), and
      the results were moderately correlated (R = 0.38). Inter-modality agreement
      between ICA and CCTA for SXScore tertiles was moderate (kappa = 0.40). The intra
      modality reproducibility of ICA and CCTA for SXScore tertiles was 0.47 and 0.51,
      respectively. CONCLUSIONS: Inter-modality agreement between CCTA and ICA for
      calculation of SXSscore is moderate but only slightly worse than intra-modality
      reproducibility for angiographic alone evaluation. Most of the observed
      variability can be assigned to the characteristic of the SXScore itself, not to
      the choice of imaging method. However, the application of CCTA for the assessment
      of SXScore should be used cautiously.

PMID- 26202530
TI  - Cardiac complications in children with Kawasaki disease in our own experience.
AB  - BACKGROUND: Kawasaki disease is the most common cause of acquired heart disease
      in children in developed countries. The incidence of Kawasaki disease varies from
      180 in Japan through 20 in United States to 5-8 in the European countries per
      100,000 children younger than 5 years of age. AIM: To evaluate cardiac
      complications in children hospitalised with Kawasaki disease. METHODS:
      Retrospective analysis of the medical records of patients hospitalised with
      Kawasaki disease in the Specialist Mother and Child Healthcare Facility in Poznan
      (Poland) in 2008-2014. The diagnosis was based on the American Heart Association
      criteria. RESULTS: Study group included 30 patients (25 boys and 5 girls). The
      mean age was 49 months; 21 (70%) children were younger than 5 years of age. All
      patients had oral mucosal lesions, while an elevated leukocyte count was observed
      in a minority of patients. Cardiac involvement was detected in 18 (60%) patients,
      aneurysms in 4 (13.3%) patients, coronary artery dilatation in 6 patients,
      pericarditis in 6 patients, mitral regurgitation in 3 patients, and aortic
      regurgitation in 2 patients. In 5 children, more than 1 cardiac abnormality was
      detected. During 12 months of follow-up, coronary artery dilatation resolved in 5
      children, and 1 patient developed aneurysm. CONCLUSIONS: Our findings suggest
      that Kawasaki disease should be considered in the differential diagnosis of
      children with prolonged fever. During the acute stage of the disease, children
      with Kawasaki disease require regular cardiac evaluation, and long-term care is
      needed when cardiovascular complications occur. A central case reporting system
      to monitor all cases of Kawasaki disease in the Polish paediatric population
      should be introduced.

PMID- 26202531
TI  - Perception of health control and self-efficacy  in heart failure.
AB  - BACKGROUND: The issue of self-perceived health control and related sense of self
      efficacy has not received any attention in patients with heart failure (HF),
      although these psychological features have been established to determine the
      patients' approach towards healthcare professionals and their recommendations,
      which strongly affects compliance. METHODS: A total of 758 patients with systolic
      HF (age: 64 +/- 11 years, men: 79%, NYHA class III-IV: 40%, ischaemic aetiology:
      61%) were included in a prospective Polish multicentre Caps-Lock-HF study. A
      Multidimensional Health Locus of Control (MHLC) scale was used to assess
      subjective perception of health control in three dimensions (internal control,
      external control by the others, and by chance); the Generalised Self Efficacy
      scale (GSES) was used to estimate subjective sense of self-efficacy; and the Beck
      Depression Inventory (BDI) was used to determine depressive symptoms. RESULTS:
      The majority of patients perceived the external control (by the others) and
      internal control of their health as high (77% and 63%, respectively) or moderate
      (22% and 36%, respectively), whereas self-efficacy was perceived as high or
      moderate (63% and 27%), which was homogenous across the whole spectrum of the HF
      cohort, being unrelated to HF severity, HF duration, the presence of co
      morbidities, and the applied treatment. The stronger the perception of internal
      health control, the higher the self-efficacy (p < 0.05); both features were
      related to less pronounced depressive symptoms (p < 0.05). CONCLUSIONS: The
      established pattern of self-perceived control of own health and self-efficacy
      indicates that patients with HF acknowledge the role of others (i.e. healthcare
      providers) and themselves in the process of the management of HF, and are
      convinced about the high efficacy of their undertaken efforts. Such evidence
      supports implementation of a partnership model of specialists' care of patients
      with HF.

PMID- 26202532
TI  - Appropriate bolus administration of glycoprotein IIb/IIIa inhibitors for patients
      with acute coronary syndromes undergoing percutaneous coronary intervention:
      intracoronary or intravenous? A comprehensive and updated meta-analysis and
      systematic review.
AB  - BACKGROUND AND AIM: This systematic review with meta-analysis sought to compare
      the efficacy and safety of intracoronary (IC) vs. intravenous (IV) administration
      of glycoprotein (GP) IIb/IIIa receptor inhibitors on clinical outcomes following
      per-cutaneous coronary intervention in patients with acute coronary syndromes (ST
      segment elevation myocardial infarction or non-ST-segment-elevation acute
      coronary syndrome). METHODS: Medline, Embase, Elsevier, and Sciences online
      databases as well as Google Scholar literature were used to select appropriate
      studies with randomised controlled design. The primary end-points were mortality
      and target vessel revascularisation (TVR), whereas the secondary end points were
      incidence of thrombolysis in myocardial infarction score 3 flow (TIMI 3 flow
      means complete perfusion in distal coronary artery bed), re-myocardial infarction
      (re-MI), major bleeding, stent thrombosis left ventricular ejection fraction
      (LVEF), and heart failure (HF). The literature search of all major databases
      retrieved 1006 stud-ies. After screening, a total of 18 trials (5812 patients)
      were identified with reported outcomes. RESULTS: Pooled analysis showed IC
      administration of GP IIb/IIIa receptor inhibitors can significantly increase LVEF
      (WMD 4.97; 95% CI 3.34-6.60; p = 0.000) and the incidence of TIMI 3 flow (OR of
      0.77; 95% CI 0.64-0.92; p = 0.005), and significantly decrease in incidence of HF
      (OR of 1.927; 95% CI 1.189-3.124; p = 0.008). Incidences of TVR, re-MI, major
      bleeding, stent thrombosis, and mortality showed no significant differences
      between the IC and IV groups. CONCLUSIONS: Overall, the most appropriate route of
      administration of GP IIb/IIIa inhibitors for patients with acute coronary
      syndromes appeared to be an IC injection that could increase LVEF and TIMI 3 flow
      and decrease the incidence of HF. Furthermore, the IC administration was not
      associated with increased adverse event rates when compared to IV injection.

PMID- 26202533
TI  - Association between socioeconomic status  and cardiovascular risk.
AB  - BACKGROUND: Cardiovascular disease (CVD) is one of the major health problems of
      the modern societies. Socioeconomic status (SES) is an important predictor of CVD
      and its risk factors. AIM: To examine whether SES is related to an increased
      cardiovascular (CV) risk in the population of southwestern Poland. METHODS: The
      study population comprised 2027 subjects, including 929 (45.8%) men and 1098
      (54.2%) women participating in the WOBASZ study. From this population, we
      selected a subgroup of 1821 subjects free from CVD, including 816 men and 1005
      women, all with defined SES. Their CV risk was estimated using the SCORE risk
      algorithm and an analysis of the relationship between SES indicators and the
      SCORE risk was performed. RESULTS: We found a negative correlation between the
      SCORE risk and SES (p = 0.0005). In the overall study group and among
      participating women, the SCORE risk was significantly lower among subjects with
      high SES (SES score > 12). This relation was also noted in men and women aged 30
      39 years (p = 0.02), women aged 30-39 years (p = 0.0001) and 40-49 years (p =
      0.04), and in men aged 70-74 years (p = 0.046). With an increase in SES, the
      proportion of high CVD risk subjects decreased significantly in the overall study
      population and in those aged 30-39 years (p = 0.01). Similar relations were
      observed in women in the entire age range and those aged 30-39 years (p = 0.01).
      We found that SES had a significant effect on the rate of high CVD risk in all
      study subgroups aged 30-39 years (odds ratio 0.57, 95% CI 0.39-0.85, p = 0.005 in
      men and women overall; odds ratio: 0.6, 95% CI 0.37-0.99, p = 0.045 in men; and
      odds ratio: 0.4, 95% CI 0.16-0.99, p = 0.01 in women). CONCLUSIONS: Socioeconomic
      status was found to be a predictor of high CVD mortality risk in men and women
      aged 30-39 years.

PMID- 26202534
TI  - The influence of obstructive sleep breathing disturbances on echocardiographic
      and pulmonary haemodynamic parameters in patients with dilated cardiomyopathy.
AB  - BACKGROUND: It is important to identify the clinical indicators of poor prognosis
      and treatable conditions that might contribute to the progression of heart
      failure (HF) and pulmonary hypertension (PH) in the group of patients with
      dilated cardiomyopathy (DCM) and concomitant obstructive sleep apnoea (OSA). AIM:
      To evaluate the influence of OSA on echocardiographic and haemodynamic parameters
      in patients with DCM, and the outcome in long-term follow-up. METHODS: We
      enrolled patients with DCM and severely impaired ejection fraction (EF < 30%).
      Each patient underwent polygraphy, echocardiography, and right heart
      catheterisation. Subjects were divided into groups based on the apnoea-hypopnoea
      index (AHI): > 0 and < 5 (group I), >= 5 and <= 15 (group II), > 15 and <= 30
      (group III), and > 30 (group IV). We compared the OSA-free (AHI < 5) subjects
      with those with OSA (AHI >= 5). The evaluated clinical end-points were death and
      orthotropic heart transplant. RESULTS: The study population comprised 51
      patients. Mean EF was 22%; 59% of patients were suffering from OSA. The increased
      severity of OSA correlated with worse pulmonary haemodynamics. Patients with OSA
      had higher mean pulmonary arterial pressure and pulmonary vascular resistance
      than individuals without OSA (p = 0.044, p = 0.032, respectively). The highest
      chamber diameters assessed in echocardiography were found in group IV (p < 0.05).
      A total of 10 end-points occurred during follow-up (8.9 +/- 5.1 months), with
      significant differences observed between groups I-IV and the highest rate in
      group IV (p < 0.001). CONCLUSIONS: The increasing severity of OSA worsens the
      prognosis of DCM patients, independently of severe HF and coexistent PH.
      Systematic OSA screening in patients with HF might facilitate identification of
      individuals at high risk of progression of pulmonary haemodynamic impairment and
      end-point rate.

PMID- 26202535
TI  - Gender-dependent profile of heart rate turbulence parameters in patients after
      acute myocardial infarction treated invasively.
AB  - BACKGROUND AND AIM: The aim of this study was to determine whether gender is
      related to differences in heart rate turbulence (HRT) parameters and the authors'
      own predefined HRT categories comprising turbulence timing (TT) in patients at
      the early stage of acute myocardial infarction (AMI) treated invasively. METHODS:
      We analysed 489 consecutive patients (147 females and 342 males, aged 63.9 +/-
      11.7 years) with AMI admitted to our department and treated invasively on
      admission to the hospital. On the fifth day after MI 24-h digital Holter
      recordings were performed to assess HRT, and the following HRT parameters were
      calculated in all patients using the HRTView pro-gram: turbulence onset (TO, %),
      slope (TS, ms/RR interval), and TT. The following values of HRT parameters were
      considered abnormal: TO >= 0, TS <= 2.5, and TT >= 10. Based on the
      abovementioned parameters, the authors defined their own HRT categories (A, B,
      C): A - comprising three normal parameters, B - one abnormal parameter, C - three
      abnormal parameters. RESULTS: TT was significantly later in women than in men:
      7.5 +/- 3.1 vs. 6.8 +/- 3.1 (p < 0.05), respectively. When analysing the authors'
      own predefined HRT categories, significant differences between women and men were
      present in the occurrence of the category C, including all three abnormal HRT
      parameters: TO, TS, and TT. CONCLUSIONS: In women worse TT was present and all
      three abnormal HRT parameters occurred more frequently. HRT in women after AMI is
      profoundly altered compared to in men. This indicates greater autonomic
      dysfunction and higher risk for sudden cardiac death in women after AMI.

PMID- 26202536
TI  - The role of baseline indirect inflammatory markers in prediction of response to
      cardiac resynchronisation therapy.
AB  - BACKGROUND: In many cardiovascular diseases (CVD), white blood cell counts with
      differentials are used to predict adverse events. Both platelet-to-lymphocyte
      ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are studied in various CVDs.
      AIM: The role of inflammatory condition assessed using routine laboratory tests
      in cardiac resynchronisation therapy (CRT) response has not been investigated
      thoroughly. Therefore, we aimed to assess the association of NLR, PLR, and
      relative lymphocyte count (L%) with response to CRT. METHODS: A total of 157
      patients (76.4% male; mean age 58.7 +/- 11.8 years) who underwent CRT
      implantation at our tertiary referral hospital were retrospectively analysed.
      RESULTS: Among included patients, a total of 50 (31.8%) patients were defined as
      "non-responders". Median NLR and PLR were significantly higher in the non
      responder group (p < 0.001), and median L% was significantly lower in the non
      responder group (p < 0.001). Also, median NLR was significantly higher in
      patients with New York heart Association (NYHA) class II-III when compared to
      patients with NYHA class I after six months of CRT implantation (p < 0.001, p =
      0.004, respectively). Correlation analysis demonstrated a positive correlation
      between paced QRS duration and NLR (p = 0.031) and a negative correlation between
      paced QRS duration and L% (p = 0.002). In addition, both NLR and L% showed
      significant correlations with post-procedural NYHA functional classes (p < 0.001;
      p = 0.008, respectively). Patients with PLR > 173.09 had a 2.9-fold and NLR >
      3.45 had a 12.2-fold increased risk of CRT nonresponse, respectively.
      CONCLUSIONS: In the current study non-responders to CRT had higher NLR and PLR
      and lower L%, which may support the deleterious effects of baseline inflammatory
      condition in advanced heart failure.

PMID- 26202537
TI  - The value of the Duke treadmill score in predicting the presence and severity of
      coronary artery disease.
AB  - BACKGROUND AND AIM: We aimed to investigate the role of the Duke treadmill score
      (DTS) in predicting the presence and severity of coronary artery disease (CAD) by
      using the SYNTAX score (SS), and also to determine the cut-off value of DTS for
      both the presence and severity of CAD. METHODS: The study population consisted of
      267 patients admitted to the outpatient clinic with chest pain, who under-went
      coronary angiography after a positive treadmill stress test. First the patients
      were divided into two groups: SS = 0 and SS > 0. Then the SS > 0 patients were
      classified into two subgroups with low (1-22) and high (> 22) SS. RESULTS: There
      was a strong negative correlation between DTS and SS (r = -072, p < 0.001). The
      area under the receiver-operating curve of DTS was 0.83 (0.77-0.88, p < 0.001)
      for predicting a significant presence of CAD. The optimal cut-off value of DTS to
      predict the significant presence of CAD was -3.7 (sensitivity of 74% and
      specificity of 73%). The area under the receiver-operating curve of DTS was 0.84
      (0.78-0.90, p < 0.001) for predicting high SS. The optimal cut-off value of DTS
      to predict high SS was -11.2 (sensitivity of 81% and specificity of 80%). DTS was
      found to be an independent predictor of high SS in multivariate analysis.
      CONCLUSIONS: DTS can predict the presence and severity of stable CAD before
      coronary angiography and may enable the estimation of the revascularisation
      method that will be required after the procedure.

PMID- 26202538
TI  - Social networks and social support for healthy eating among Latina breast cancer
      survivors: implications for social and behavioral interventions.
AB  - PURPOSE: Little is known about Latina breast cancer survivors' social networks or
      their perceived social support to achieve and maintain a healthy diet. This paper
      describes the social networks and perceived support for healthy eating in a
      sample of breast cancer survivors of predominantly Dominican descent living in
      New York City. METHODS: Spanish-speaking Latina breast cancer survivors enrolled
      in a randomized controlled trial of a culturally tailored dietary intervention.
      Social networks were assessed using Cohen's Social Network Index and a modified
      General Social Survey Social Networks Module that included assessments of shared
      health promoting behaviors. Perceived social support from family and friends for
      healthy, food-related behaviors was assessed. RESULTS: Participants' networks
      consisted predominantly of family and friends. Family members were more likely
      than other individuals to be identified as close network members. Participants
      were more likely to share food-related activities than exercise activities with
      close network members. Perceived social support for healthy eating was high,
      although perceived support from spouses and children was higher than support from
      friends. Despite high levels of perceived support, family was also identified as
      a barrier to eating healthy foods by nearly half of women. CONCLUSIONS: Although
      friends are part of Latina breast cancer survivors' social networks, spouses and
      children may provide greater support for healthy eating than friends.
      IMPLICATIONS FOR CANCER SURVIVORS: Involving family members in dietary
      interventions for Latina breast cancer survivors may tap into positive sources of
      support for women, which could facilitate uptake and maintenance of healthy
      eating behaviors.

PMID- 26202539
TI  - Efficacy of the Omega-3 Index in predicting non-alcoholic fatty liver disease in
      overweight and obese adults: a pilot study.
AB  - Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of CVD in
      otherwise healthy individuals. Low n-3 PUFA intake has been associated with the
      presence of NAFLD; however, the relationship between a biomarker of n-3 status -
      the Omega-3 Index - and liver fat is yet to be elucidated. A total of eighty
      overweight adults (fifty-six men) completed the anthropometric and biochemical
      measurements, including the Omega-3 Index, and underwent proton magnetic
      resonance spectroscopy assessment of liver fat. Bivariate correlations and
      multiple regression analyses were performed with reference to prediction of liver
      fat percentage. The mean Omega-3 Index was high in both NAFLD (intrahepatic lipid
      concentration>=5.5 %) and non-NAFLD groups. The Omega-3 Index, BMI, waist
      circumference, glucose, insulin, TAG, high-sensitive C-reactive protein (hsCRP)
      and alanine aminotransferase (ALT) were positively correlated, and HDL and
      erythrocyte n-6:n-3 ratio negatively correlated with liver fat concentration.
      Regression analysis found that simple anthropometric and demographic variables
      (waist, age) accounted for 31 % of the variance in liver fat and the addition of
      traditional cardiometabolic blood markers (TAG, HDL, hsCRP and ALT) increased the
      predictive power to 43 %. The addition of the novel erythrocyte fatty acid
      variable (Omega-3 Index) to the model only accounted for a further 3 % of the
      variance (P=0.049). In conclusion, the Omega-3 Index was associated with liver
      fat concentration but did not improve the overall capacity of demographic,
      anthropometric and blood markers to predict NAFLD. 

PMID- 26202540
TI  - Scale Up of Pan Coating Process Using Quality by Design Principles.
AB  - Scale up of pan coating process is of high importance to the pharmaceutical and
      food industry. The number of process variables and their interdependence in a pan
      coating process can make it a rather complex scale-up problem. This review
      discusses breaking down the coating process variables into three main categories:
      pan-related, spray-related, and thermodynamic-related factors. A review on how to
      scale up each of these factors is presented via two distinct strategies-
      "macroscopic" and "microscopic" scale-up. In a Quality by Design paradigm, where
      an increased process understanding is required, there is increased emphasis on
      "microscopic" scale-up, which by definition ensures a more reproducible process
      and thereby robust scale-up. This article also reviews the various existing and
      new modeling and process analytical technology tools that can provide additional
      information to facilitate a more fundamental understanding of the coating
      process.

PMID- 26202541
TI  - Imaging the dynamic platelet-neutrophil response in sterile liver injury and
      repair in mice.
AB  - Although platelets have been extensively studied in hemostasis and inflammation,
      their role is not well understood in sterile liver injury and repair. Using a
      thermally induced focal liver injury and repair model and multichannel spinning
      disk confocal microscopy allowed visualization of the dynamic behavior of
      platelets and neutrophils in this insult. Platelets instantaneously adhered to
      molecularly altered sinusoidal endothelium adjacent to the afflicted area, paving
      approximately 200 um abutting the injury. Platelets remained adherent for at
      least 4 hours, but dissipated by 8 hours. The early recruitment occurred by
      GPIIbIIIa (CD41) and the later recruitment was dependent upon both GPIIbIIIa and
      GPIb (CD42B). Platelets did not occlude the vessels, but rather paved the altered
      endothelium. Endothelin-induced vasoconstriction by hepatic stellate cells, and
      not platelet accumulation or coagulation, was responsible for temporarily
      restricted perfusion around the injury. Neutrophils crawled into the injury from
      significant distances through the sinusoids. The crawling neutrophils required
      the platelet-paved endothelium given that very little neutrophil recruitment was
      noted in thrombocytopenic or CD41-deficient mice. As platelets slowly dissipated,
      neutrophil recruitment was also halted. Previous work suggested that platelets
      binding to immobilized neutrophils induced neutrophil extracellular trap (NET)
      formation in response to infection as well as during thrombosis and other forms
      of sterile injury. In this model of neutrophils crawling on immobilized
      platelets, very few NETs were observed and no additional injury was noted. In
      fact, GPIIbIIIa-deficient mice had delayed repair. CONCLUSION: In a liver model
      of sterile injury and repair, platelets play a critical role in forming a
      substratum and pave the way for neutrophils to enter the injured site for
      subsequent repair.

PMID- 26202542
TI  - Psychological and psychosocial interventions for cannabis cessation in adults: a
      systematic review short report.
AB  - BACKGROUND: Cannabis is the most commonly used illicit drug worldwide. Cannabis
      dependence is a recognised psychiatric diagnosis, often diagnosed via the
      Diagnostic and Statistical Manual of Mental Disorders criteria and the
      International Classification of Diseases, 10th Revision. Cannabis use is
      associated with an increased risk of medical and psychological problems. This
      systematic review evaluates the use of a wide variety of psychological and
      psychosocial interventions, such as motivational interviewing (MI), cognitive
      behavioural therapy (CBT) and contingency management. OBJECTIVE: To
      systematically review the clinical effectiveness of psychological and
      psychosocial interventions for cannabis cessation in adults who use cannabis
      regularly. DATA SOURCES: Studies were identified via searches of 11 databases
      [MEDLINE, EMBASE, Cochrane Controlled Trials Register, Health Technology
      Assessment (HTA) database, Database of Abstracts of Reviews of Effects, Cochrane
      Database of Systematic Reviews, NHS Economic Evaluation Database, PsycINFO, Web
      of Science Conference Proceedings Citation Index, ClinicalTrials.gov and
      metaRegister of Current Controlled Trials] from inception to February 2014,
      searching of existing reviews and reference tracking. METHODS: Randomised
      controlled trials (RCTs) assessing psychological or psychosocial interventions in
      a community setting were eligible. Risk of bias was assessed using adapted
      Cochrane criteria and narrative synthesis was undertaken. Outcomes included
      change in cannabis use, severity of cannabis dependence, motivation to change and
      intervention adherence. RESULTS: The review included 33 RCTs conducted in various
      countries (mostly the USA and Australia). General population studies: 26 studies
      assessed the general population of cannabis users. Across six studies, CBT (4-14
      sessions) significantly improved outcomes (cannabis use, severity of dependence,
      cannabis problems) compared with wait list post treatment, maintained at 9 months
      in the one study with later follow-up. Studies of briefer MI or motivational
      enhancement therapy (MET) (one or two sessions) gave mixed results, with some
      improvements over wait list, while some comparisons were not significant. Four
      studies comparing CBT (6-14 sessions) with MI/MET (1-4 sessions) also gave mixed
      results: longer courses of CBT provided some improvements over MI. In one small
      study, supportive-expressive dynamic psychotherapy (16 sessions) gave significant
      improvements over one-session MI. Courses of other types of therapy (social
      support group, case management) gave similar improvements to CBT based on limited
      data. Limited data indicated that telephone- or internet-based interventions
      might be effective. Contingency management (vouchers for abstinence) gave
      promising results in the short term; however, at later follow-ups, vouchers in
      combination with CBT gave better results than vouchers or CBT alone. Psychiatric
      population studies: seven studies assessed psychiatric populations
      (schizophrenia, psychosis, bipolar disorder or major depression). CBT appeared to
      have little effect over treatment as usual (TAU) based on four small studies with
      design limitations (both groups received TAU and patients were referred). Other
      studies reported no significant difference between types of 10-session therapy.
      LIMITATIONS: Included studies were heterogeneous, covering a wide range of
      interventions, comparators, populations and outcomes. The majority were
      considered at high risk of bias. Effect sizes were reported in different formats
      across studies and outcomes. CONCLUSIONS: Based on the available evidence,
      courses of CBT and (to a lesser extent) one or two sessions of MI improved
      outcomes in a self-selected population of cannabis users. There was some evidence
      that contingency management enhanced long-term outcomes in combination with CBT.
      Results of CBT for cannabis cessation in psychiatric populations were less
      promising, but may have been affected by provision of TAU in both groups and the
      referred populations. Future research should focus on the number of CBT/MI
      sessions required and potential clinical effectiveness and cost-effectiveness of
      shorter interventions. CBT plus contingency management and mutual aid therapies
      warrant further study. Studies should consider potential effects of recruitment
      methods and include inactive control groups and long-term follow-up. TAU arms in
      psychiatric population studies should aim not to confound the study intervention.
      STUDY REGISTRATION: This study is registered as PROSPERO CRD42014008952. FUNDING:
      The National Institute for Health Research HTA programme.

PMID- 26202543
TI  - Controlled Silylation of Nanofibrillated Cellulose in Water: Reinforcement of a
      Model Polydimethylsiloxane Network.
AB  - A comparative approach for the surface silylation of nanofibrillated cellulose
      (NFC) in water is proposed through an environmentally friendly sol-gel route
      based on alkoxysilanes. NFC suspensions were freeze-dried under controlled
      conditions in the presence of methyltrimethoxysilane used as a model
      alkoxysilane. Two different protocols that involve different pH values (0.4 and
      4) and post-treatment procedures were investigated and compared. Protocol 1 led
      to a network of nanofibrils in which polysiloxane particles were dispersed, and
      protocol 2 produced a scaffold of cellulosic fibrils coated by a polysiloxane
      layer bonded firmly to the cellulosic substrate. Different from protocol 1,
      protocol 2 imparted the cellulosic material with hydrophobic properties and
      improved its thermal stability. Moreover, if 1 wt % of fibrils treated by
      protocol 2 were incorporated into a model polydimethylsiloxane network,
      substantial improvements of the static and dynamic mechanical properties of the
      composite were noted. 

PMID- 26202544
TI  - Myocardial protection from ischemia-reperfusion injury post coronary
      revascularization.
AB  - Effective primary and secondary prevention and advances in cardiac surgery have
      significantly improved the care and outcomes of patients with myocardial
      ischemia. While timely reperfusion has proved to be an invaluable tool, ischemia
      reperfusion injury represents a mechanism that may limit its effectiveness.
      Numerous experimental studies have shown effective protection from ischemia
      reperfusion injury in animal models, but translation into clinical practice has
      been less successful. This article summarizes the role of ischemia-reperfusion
      injury in the pathophysiology of ischemic heart disease and gives an overview of
      the various modalities that have been developed in order to provide myocardial
      protection from reperfusion injury in clinical practice. 

PMID- 26202545
TI  - Psychopharmacologic Services for Homeless Veterans: Comparing Psychotropic
      Prescription Fills Among Homeless and Non-Homeless Veterans with Serious Mental
      Illness.
AB  - Using national Veterans Health Administration (VHA) administrative data, this
      study evaluated differences in psychotropic medication use between homeless and
      non-homeless adults with serious mental illness (SMI) who used VHA services in
      2010. The adjusted mean number of psychotropic prescription fills associated with
      homeless individuals were identified using regression models adjusted for socio
      demographics, diagnoses, and use of health services. Of the 876,989 individuals
      with SMI using VHA services, 7.2 % were homeless at some time during 2010. In
      bivariate analysis, homeless individuals filled more psychotropic medication
      prescriptions compared with non-homeless individuals. However, after adjusting
      for potentially confounding variables, homeless individuals were found to have
      filled 16.2 % fewer prescriptions than non-homeless individuals when all
      psychotropics were analyzed together (F = 6947.1, p < .001) and for most
      individual classes of psychotropics. Greater use of residential/inpatient mental
      health services by the homeless was the most important single factor associated
      with filling more psychotropic prescriptions than non-homeless individuals. 

PMID- 26202546
TI  - Why do mental health consumers who receive rehabilitation services, are not using
      them? A Qualitative Investigation of Users' Perspectives in Israel.
AB  - A recovery-oriented approach to mental health involves creating person centered
      services and enhancing engagement in psychiatric rehabilitation. Israel's
      Rehabilitation in the Community of Persons with Mental Disabilities Law is a
      progressive initiative that shifted the locus of psychiatric care to community
      care supporting individualized rehabilitation and recovery-oriented processes.
      Yet over a quarter of applicants do not implement their assigned rehabilitation
      plans and services. This qualitative study investigated reasons and experiences
      related to lack of utilization from applicants' perspectives. Fifteen service
      users were interviewed face to face in semi-structured interviews analyzed using
      Grounded theory approach. Seven categories emerged: (1) Lack of knowledge and
      orientation; (2) Negative perceptions about rehabilitation services (3) Lack of
      active participation/shared decision-making; (4) Not feeling heard by the
      committee; (5) Lack of congruence between participants' goals and committee's
      final decisions; (6) Lack of escorting professionals' competencies; and (7)
      Family members' influence. The results are interpreted at the structural and
      human process levels. Suggestions are provided for augmenting systemic procedures
      and human interactions processes.

PMID- 26202547
TI  - Suicidal Ideation Among Adults with Disability in Western Canada: A Brief Report.
AB  - This study investigated prevalence and risk factors for suicidal ideation among
      adults with self-reported disability in Western Canada. The method was secondary
      data analysis utilising the Canadian Community Health Survey. The odds of 12
      month suicidal ideation are 3.5 times greater for adults with self-reported
      disability compared with non-disabled adults, controlling for age, sex,
      ethnicity, and psychiatric morbidity. The heightened risk of ideation among
      adults with self-reported disability is partially explained by social adversity,
      including food insecurity and low sense of community belonging. Reducing suicide
      risk among adults with disability requires a broad-spectrum approach, including
      mental health care, and strategies to ameliorate social and economic hardship.

PMID- 26202548
TI  - Laser microdissection-based gene expression analysis in the aleurone layer and
      starchy endosperm of developing rice caryopses in the early storage phase.
AB  - BACKGROUND: Rice endosperm is composed of aleurone cells in the outermost layers
      and starchy endosperm cells in the inner part. The aleurone layer accumulates
      lipids, whereas starchy endosperm mainly accumulates starch. During the ripening
      stage, the starch accumulation rate is known to be asynchronous, depending on the
      position of the starchy endosperm. Different physiological and molecular
      mechanisms are hypothesized to underlie the qualitative and quantitative
      differences in storage products among developing rice endosperm tissues. RESULTS:
      Target cells in aleurone layers and starchy endosperm were isolated by laser
      microdissection (LM), and RNAs were extracted from each endosperm tissue in the
      early storage phase. Genes important for carbohydrate metabolism in developing
      endosperm were analyzed using qRT-PCR, and some of the genes showed specific
      localization in either tissue of the endosperm. Aleurone layer-specific gene
      expression of a sucrose transporter, OsSUT1, suggested that the gene functions in
      sucrose uptake into aleurone cells. The expression levels of ADP-glucose
      pyrophosphorylase (AGPL2 and AGPS2b) in each endosperm tissue spatially
      corresponded to the distribution of starch granules differentially observed among
      endosperm tissues. By contrast, expressions of genes for sucrose cleavage
      hexokinase, UDP-glucose pyrophosphorylase, and phosphoglucomutase-were observed
      in all endosperm tissues tested. Aleurone cells predominantly expressed mRNAs for
      the TCA cycle and oxidative phosphorylation. This finding was supported by the
      presence of oxygen (8 % concentration) and large numbers of mitochondria in the
      aleurone layers. In contrast, oxygen was absent and only a few mitochondria were
      observed in the starchy endosperm. Genes for carbon fixation and the GS/GOGAT
      cycle were expressed highly in aleurone cells compared to starchy endosperm.
      CONCLUSIONS: The transcript level of AGPL2 and AGPS2b encoding ADP-glucose
      pyrophosphorylase appears to regulate the asynchronous development of starch
      granules in developing caryopses. Aleurone cells appear to generate, at least
      partially, ATP via aerobic respiration as observed from specific expression of
      identified genes and large numbers of mitochondria. The LM-based expression
      analysis and physiological experiments provide insight into the molecular basis
      of the spatial and nutritional differences between rice aleurone cells and
      starchy endosperm cells.

PMID- 26202549
TI  - The Rice Floral Repressor Early flowering1 Affects Spikelet Fertility By
      Modulating Gibberellin Signaling.
AB  - BACKGROUND: Gibberellic acid (GA; or gibberellin) affects the development of
      floral organs, especially anthers and pollen, and perturbation of development of
      male floral organs can cause sterility. Many studies of GA signaling have
      concentrated on anther development, but the effect of GA on grain production
      remains to be examined. RESULTS: Using a cross of 'Milyang23 (M23)', which has a
      functional allele of Early flowering1 (EL1), and 'H143', which has a
      nonfunctional el1 allele, we generated heterogeneous inbred family-near isogenic
      lines (HNILs) that are homozygous for EL1 [HNIL(M23)] or el1 [HNIL(H143)]. Here,
      we found that HNIL(H143) exhibited anther deformities and low pollen viability.
      The expression of GAMYB, a major activator of GA signaling, and its downstream
      genes CYP703A3 and KAR, mainly involved in pollen formation, increased abnormally
      during spikelet development; this activation of GA signaling may cause the
      sterility. To confirm the negative effect of the el1 mutation on spikelet
      fertility, we examined a line carrying a T-DNA insertion el1 mutant [hereafter
      ZH11(el1)] and its parental cultivar 'Zhonghua11 (ZH11)'. ZH11(el1) showed nearly
      identical defects in anther development and pollen viability as HNIL(H143),
      leading to decreased seed setting rate. However, the elite japonica cultivar
      Koshihikari, which has a nonfunctional el1 allele for early flowering in long
      days, produces fertile spikelets and normal grain yields, like other elite
      japonica cultivars. This indicates that as-yet-unknown regulator(s) that can
      overcome the male sterile phenotype of the el1 mutation must have been introduced
      into Koshihikari. CONCLUSIONS: The el1 mutation contributes to early flowering in
      japonica rice under long days but fails to limit GA signaling, thus negatively
      affecting spikelet fertility, which results in a loss of grain yield. Thus, EL1
      is essential for photoperiod sensitivity in flowering as well as spikelet
      fertility in grain production.

PMID- 26202550
TI  - Prevalence and Clinicopathological Characteristics of BRAF Mutations in Chinese
      Patients with Lung Adenocarcinoma.
AB  - BACKGROUND: This study was designed to identify the prevalence of BRAF mutations
      in Chinese patients with lung adenocarcinoma, and to reveal the association
      between BRAF mutations and clinicopathological characteristics in these patients.
      METHODS: From October 2007 to February 2013, patients with newly diagnosed
      primary lung adenocarcinoma were detected for mutations in BRAF, EGFR, KRAS, HER2
      and ALK. Clinicopathological characteristics, including sex, age, TNM stage,
      tumor differentiation, smoking status, histological subtypes, and survival
      information were analyzed. RESULTS: Of 1358 patients with lung adenocarcinoma, 20
      patients were harboring BRAF mutations, including five BRAF V600E mutations and
      15 BRAF non-V600E mutations. Among these, BRAF N581I and BRAF G593S were newly
      reported. BRAF mutations were associated with smoking status (odds ratio 3.28; 95
      % CI 1.33-8.08; p = 0.008). In patients less than 60 years of age, BRAF mutations
      tended to have poor differentiation in tumor samples (70.0 vs. 35.1 %; p =
      0.014), and were more likely to relapse (70 vs. 28 %; p = 0.008). A significant
      difference was found in relapse-free survival (RFS) between BRAF mutations and
      other mutations, but not in overall survival. CONCLUSIONS: The prevalence of BRAF
      mutations in Chinese patients with lung adenocarcinoma was approximately 1.5 %.
      BRAF mutations were more frequent in current smokers. Patients harboring BRAF
      mutations had a higher rate of recurrence and worse RFS compared with other
      patients.

PMID- 26202551
TI  - The Influence of Radiology Image Consultation in the Surgical Management of
      Breast Cancer Patients.
AB  - BACKGROUND: Patients referred to comprehensive cancer centers arrive with
      clinical data requiring review. Radiology consultation for second opinions often
      generates additional imaging requests; however, the impact of this service on
      breast cancer management remains unclear. We sought to identify the incidence of
      additional imaging requests and the effect additional imaging has on patients'
      ultimate surgical management. METHODS: Between November 2013 and March 2014, 153
      consecutive patients with breast cancer received second opinion imaging reviews
      and definitive surgery at our cancer center. We identified the number of
      additional imaging requests, the number of fulfilled requests, the modality of
      additional imaging completed, the number of biopsies performed, and the number of
      patients whose management was altered due to additional imaging results. RESULTS:
      Of 153 patients, the mean age was 55 years; 98.9% were female; 23.5% (36) had in
      situ carcinoma (35 DCIS/1 LCIS), and 76.5% (117) had invasive carcinoma.
      Additional imaging was suggested for 47.7% (73/153) of patients. After
      multidisciplinary consultation, 65.8% (48/73) of patients underwent additional
      imaging. Imaging review resulted in biopsy in 43.7% (21/48) of patients and
      ultimately altered preliminary treatment plans in 37.5% (18/48) of patients (Fig.
      1). Changes in management included: conversion to mastectomy or breast
      conservation, neoadjuvant therapy, additional wire placement, and need for
      contralateral breast surgery. Fig. 1 Impact of second-opinion imaging reviews on
      the management of breast cancer patients CONCLUSIONS: Our analysis of second
      opinion imaging consultation demonstrates the significant value that this service
      has on breast cancer management. Overall, 11.7% (18/153) of patients who
      underwent breast surgery had management changes as a consequence of radiologic
      imaging review.

PMID- 26202552
TI  - Modern Trends in the Surgical Management of Paget's Disease.
AB  - PURPOSE: We examined the incidence and modern national trends in the management
      of Paget's disease (PD), including the use of breast-conserving surgery (BCS),
      mastectomy, axillary surgery, and receipt of radiotherapy. METHODS: Using
      surveillance, epidemiology and end results (SEER) data, we identified 2631
      patients diagnosed with PD during 2000-2011. Of these patients, 185 (7%) had PD
      of the nipple only, 953 (36.2%) had PD with ductal carcinoma in situ (PD-DCIS),
      and 1493 (56.7%) had PD with invasive ductal carcinoma (PD-IDC). Trends in age
      adjusted incidence, primary surgery, sentinel lymph node biopsy (SLNB), and
      axillary lymph node dissection were examined. Multivariable logistic regression
      was used to evaluate factors associated with receipt of BCS and radiotherapy.
      RESULTS: A decrease in the age-adjusted incidence of PD occurred from 2000 to
      2011 (-4.3% per year, p < 0.05). The overall rates of mastectomy in the PD only,
      PD-DCIS, and PD-IDC groups were 47, 69, and 88.9%, respectively. Only in the PD
      IDC group did the proportion of patients undergoing BCS increase significantly,
      from 8.5% in 2000 to 15.7% in 2011 (p = 0.01). Of those who underwent axillary
      surgery, the proportion of patients undergoing SLNB increased from 2000 to 2011.
      In adjusted analyses, Paget's subgroup, older age, central tumor location,
      low/intermediate grade, tumor size <2.0 cm, SEER region, and year of diagnosis
      after 2006 were significantly associated with receipt of BCS. CONCLUSIONS: The
      incidence of Paget's disease has decreased over time while modern trends in local
      therapy suggest that BCS, SLNB, and adjuvant radiotherapy remain underutilized.

PMID- 26202553
TI  - Intraoperative Assessment of Final Margins with a Handheld Optical Imaging Probe
      During Breast-Conserving Surgery May Reduce the Reoperation Rate: Results of a
      Multicenter Study.
AB  - BACKGROUND: A multicenter, prospective, blinded study was performed to test the
      feasibility of using a handheld optical imaging probe for the intraoperative
      assessment of final surgical margins during breast-conserving surgery (BCS) and
      to determine the potential impact on patient outcomes. METHODS: Forty-six
      patients with early-stage breast cancer (one with bilateral disease) undergoing
      BCS at two study sites, the Johns Hopkins Hospital and Anne Arundel Medical
      Center, were enrolled in this study. During BCS, cavity-shaved margins were
      obtained and the final margins were examined ex vivo in the operating room with a
      probe incorporating optical coherence tomography (OCT) hardware and
      interferometric synthetic aperture microscopy (ISAM) image processing. Images
      were interpreted after BCS by three physicians blinded to final pathology
      reported margin status. Individual and combined interpretations were assessed.
      Results were compared to conventional postoperative histopathology. RESULTS: A
      total of 2,191 images were collected and interpreted from 229 shave margin
      specimens. Of the eight patients (17 %) with positive margins (0 mm), which
      included invasive and in situ diseases, the device identified all positive
      margins in five (63%) of them; reoperation could potentially have been avoided in
      these patients. Among patients with pathologically negative margins (>0 mm), an
      estimated mean additional tissue volume of 10.7 ml (approximately 1% of overall
      breast volume) would have been unnecessarily removed due to false positives.
      CONCLUSIONS: Intraoperative optical imaging of specimen margins with a handheld
      probe potentially eliminates the majority of reoperations.

PMID- 26202554
TI  - Assessment of Practice Patterns Following Publication of the SSO-ASTRO Consensus
      Guideline on Margins for Breast-Conserving Therapy in Stage I and II Invasive
      Breast Cancer.
AB  - BACKGROUND: The recently published SSO-ASTRO consensus guideline on margins
      concluded "no ink on tumor" is the standard for an adequate margin. This study
      was conducted to determine how this guideline is aligned with current clinical
      practice. METHODS: A survey was sent to 3057 members of the American Society of
      Breast Surgeons. Questions assessed respondents' clinical practice type and
      duration, familiarity with the guideline, and preferences for margin re-excision.
      RESULTS: Of those surveyed, 777 (25%) responded. Most (92%) indicated familiarity
      with the guideline. Of these respondents, the majority (n = 678, or 94.7%) would
      re-excise all or most of the time when tumor extended to the inked margin. Very
      few (n = 9, or 1.3%) would re-excise all or most of the time when tumor was
      within 2 mm of the margin. Over 12 % (n = 90) would re-excise all or most of the
      time for a triple-negative tumor within 1 mm of the margin, whereas 353 (49.6%)
      would re-excise all or most of the time when imaging and pathology were
      discordant, and tumor was within 1 mm of multiple margins. Finally, 330 (45.8%)
      would re-excise all or most of the time when multiple foci of ductal carcinoma in
      situ extended to within 1 mm of multiple inked margins. CONCLUSIONS: Surgeons are
      in agreement to re-excise margins when tumor touches ink and generally not to
      perform re-excisions when tumor is close to (but not touching) the inked margin.
      For more complex scenarios, surgeons are utilizing their individual clinical
      judgment to determine the need for re-excision.

PMID- 26202555
TI  - Presidential Address: "A Part of the Main".

PMID- 26202557
TI  - Nipple-Sparing Mastectomy in Irradiated Breasts: Selecting Patients to Minimize
      Complications.
AB  - BACKGROUND: Nipple-sparing mastectomies (NSM) are increasingly common because of
      their cosmetic advantage. Radiotherapy (RT) has been a relative contraindication
      to immediate reconstruction because of concerns about increased complications. We
      aimed to evaluate outcomes of NSM plus immediate reconstruction in irradiated
      breasts and to determine additional risk factors for complications. METHODS: We
      retrospectively reviewed NSM with immediate reconstruction from 2007 to 2013 at
      our institution. Complications were broken down into several categories.
      Potential risk factors for complications were evaluated. RESULTS: There were 982
      NSM: 816 had no RT, 67 had prior RT, and 97 had postmastectomy radiotherapy
      (PMRT). Compared to breasts with no RT, both prior RT and PMRT increased overall
      complications (10.2 vs. 21.7 and 17.5%, p = 0.003, 0.03, respectively) and nipple
      loss (0.9 vs. 4.3 and 4.1%, p = 0.04, 0.02, respectively), while PMRT increased
      rate of reconstruction failure (2.2 vs. 8.2%, p = 0.003). On multivariate
      regression analysis, prior RT [odds ratio (OR) 2.53, p = 0.006], PMRT (OR 2.29, p
      = 0.015), age >55 years (OR 2.03, p = 0.04), breast volume >=800 cm(3) (OR 1.96,
      p = 0.04), smoking (OR 2.62, p = 0.001), and periareolar incision (OR 1.74, p =
      0.03) were independent risk factors for complications requiring surgical
      revision. In irradiated breasts, complication rates were 13.4% without further
      risk factors and 17.5, 50, and 66.7% when 1, 2, and >=3 additional independent
      risk factors were present, respectively (p < 0.001). CONCLUSIONS: Although
      complication rates were higher in irradiated breasts, reconstruction failure and
      nipple/areola necrosis was infrequent. RT should not be a contraindication to
      NSM. Preoperative identification of risk factors and appropriate patient
      selection may reduce complication rates.

PMID- 26202556
TI  - Adjuvant Endocrine Therapy in Patients with Ductal Carcinoma In Situ: A
      Population-Based Retrospective Analysis from 2005 to 2012 in the National Cancer
      Data Base.
AB  - BACKGROUND: Adjuvant endocrine therapy (AET) has been shown to reduce the risk of
      second breast cancer events in women with ductal carcinoma in situ (DCIS). There
      is no population-level evaluation of AET use in DCIS patients after standardized
      reporting of estrogen receptor (ER) status in cancer registries in 2004. METHODS:
      We conducted a retrospective cohort study of women with DCIS in the National
      Cancer Data Base between 2005 and 2012. Patient, tumor, and treatment
      characteristics as well as temporal trends associated with receipt of AET were
      evaluated by generalized linear regression. RESULTS: Among 206,255 DCIS patients,
      36.5% received AET. Fewer than half of ER-positive patients (n = 62,146, 46.4%)
      received AET, with a modest but significant increase over time (43.6% in 2005 to
      47.5% in 2012; unadjusted p trend <0.001). AET decreased among ER-negative
      patients (8.9-6.5%, p trend <0.001) over the same time period. On multivariate
      analysis, younger (<40 years) and older (>=70 years) women were less likely to
      receive AET than 50- to 59-year-old women (<40 years: relative risk 0.86, 95%
      confidence interval 0.82-0.89; >=70 years: relative risk 0.79, 95% confidence
      interval 0.77-0.81). ER-positive status conferred a 6.15-fold higher likelihood
      of receiving AET compared to ER-negative status (95% confidence interval 5.81
      6.50). Women who underwent breast-conserving surgery (BCS) with adjuvant
      radiotherapy were most likely to receive AET. CONCLUSIONS: Receipt of AET is
      relatively low in the group of women most likely to benefit from its use, namely
      ER-positive patients who underwent BCS. Significant variation exists with respect
      to patient, tumor, site, and treatment factors. More tolerable drugs or clearer
      guideline recommendations may increase use.

PMID- 26202558
TI  - Local Infiltration of Liposomal Bupivacaine for Pain Control in Patients
      Undergoing Mastectomy with Immediate Tissue Expander Reconstruction.
AB  - Mastectomy with immediate tissue expander reconstruction is associated with
      postoperative pain, nausea, and vomiting. Various techniques of perioperative and
      postoperative pain control have been described. Our standard of care for
      postsurgical pain management in patients undergoing mastectomy with immediate
      tissue expander reconstruction has been preoperative ultrasound-guided
      paravertebral block. Recent literature demonstrating the opioid-sparing benefits
      of liposomal bupivacaine has directed two of our plastic surgeons to pilot its
      use in immediate tissue expander reconstruction. In the accompanying video, we
      present our technique of intraoperative local infiltration of liposomal
      bupivacaine into the base of mastectomy skin flaps, serratus fascia, and
      periaxillary tissue after completion of the mastectomy and before tissue expander
      placement into the reconstruction pocket. 

PMID- 26202559
TI  - Oncoplastic Split Reduction with Intraoperative Radiation Therapy.

PMID- 26202560
TI  - Controversies in Radiation Oncology for Early-Stage Breast Cancer.
AB  - Multiple randomized trials, as well as a meta-analysis of these studies, have
      confirmed the equivalence of breast-conservation and mastectomy. In addition, in
      unselected populations, adjuvant radiation therapy following lumpectomy has been
      shown to decrease in-breast recurrence and improve overall survival. However,
      radiation has morbidity, and is costly and inconvenient. Multiple efforts to
      minimize treatment have been studied, including omitting radiation in low-risk
      populations, as well as in those with significant competing risks. Central to
      these efforts has been an increased awareness of the inherent biology, allowing
      treatment to be more precisely tailored to the risks posed by each individual
      patient's disease. In addition, an improved understanding of the radio
      responsiveness of both tumor and adjacent normal tissue has permitted safe use of
      short-course (hypofractionated) radiation. Studies are ongoing to determine the
      most appropriate candidates for both hypofractionated treatment and omission of
      radiation entirely. The optimal management of ductal carcinoma in situ is also a
      subject of intense study. Multiple trials have attempted to identify patients who
      can safely forego radiation and, more recently, molecular predictors of
      recurrence have been developed to further fine-tune this low-risk population. 

PMID- 26202561
TI  - Neoadjuvant Chemotherapy for Breast Cancer, Is Practice Changing? A Population
      Based Review of Current Surgical Trends.
AB  - INTRODUCTION: Neoadjuvant chemotherapy in breast cancer is used to downstage
      locally advanced and inoperable tumors. Expanded benefits of neoadjuvant
      chemotherapy include downstaging of tumors to allow breast-conserving surgery
      (BCS) and assessment of in vivo tumor response. We sought to identify patterns
      and predictors of neoadjuvant chemotherapy use to determine if this has
      translated into population-level clinical practice. METHODS: All patients
      undergoing surgery for invasive breast cancer between January 2012 and June 2014
      were identified from our provincial synoptic operating room database. Data
      regarding patient demographics, hospital, operating surgeon, preoperative tumor
      characteristics, neoadjuvant treatment, and type of surgery performed were
      collected. Descriptive statistics and multivariable analysis were used to
      identify predictors of neoadjuvant chemotherapy. RESULTS: A total of 4186
      patients were identified, 363 (8.53%) of whom underwent neoadjuvant chemotherapy.
      A significant increase was seen in the use of neoadjuvant chemotherapy over time.
      In multivariable analysis, neoadjuvant chemotherapy was associated with
      prechemotherapy tumor size, multicentricity, lymph node positivity, and
      decreasing patient age. In addition, there was significant variability in
      neoadjuvant chemotherapy use between operating surgeons. Of those patients who
      underwent neoadjuvant chemotherapy, 68.9% were not pretreatment candidates for
      BCS. At the time of definitive surgery, 72.1% had mastectomy, with 18.7% opting
      for contralateral prophylactic mastectomy. As reported, this was due to the tumor
      being advanced/too large (50.4%), patient preference (12.6%), multicentricity
      (8.8%) and margins, genetics, and previous radiotherapy (4%). CONCLUSIONS: A
      significant increase in the use of neoadjuvant chemotherapy over time was
      identified, and treatment with mastectomy as definitive surgical management
      remained high. There was significant variability in neoadjuvant chemotherapy use
      by the operating surgeons, in addition to factors generally associated with more
      locally advanced/aggressive tumors.

PMID- 26202562
TI  - Chemoprevention for Breast Cancer.
AB  - BACKGROUND: Many women at increased risk for breast cancer could benefit from
      preventive therapy. Preventive therapy options for breast cancer risk reduction
      have expanded in the last few years to include both selective receptor modulators
      (tamoxifen and raloxifene) and aromatase inhibitors (anastrozole and exemestane).
      METHODS: Risk factors that place women at high risk for breast cancer, as well as
      risk calculation models appropriate for the selection of candidates for
      preventive therapy, are presented, followed by a review of current guidelines for
      chemoprevention and results of chemoprevention trials. RESULTS: The modified Gail
      model or Breast Cancer Risk Assessment Tool is the most widely utilized risk
      assessment calculator to determine eligibility for chemoprevention. Women most
      likely to benefit from preventive therapy include those at high risk under the
      age of 50 years and those with atypical hyperplasia. Physician and patient
      barriers limit widespread acceptance and adherence to preventive therapy.
      CONCLUSIONS: Published guidelines on chemoprevention for breast cancer have been
      updated to increase awareness and encourage discussion between patients and their
      physicians regarding evidence-based studies evaluating the benefits of preventive
      options for women at increased risk for breast cancer. However, even with
      increasing awareness and established benefits of preventive therapy, the uptake
      of chemoprevention has been low, with both physician and patient barriers
      identified. It is prudent that these barriers be overcome to enable high-risk
      women with a favorable risk-to-benefit ratio to be offered chemoprevention to
      reduce their likelihood of developing hormone receptor-positive breast cancer.

PMID- 26202563
TI  - Once is Rarely Enough: A Population-Based Study of Reoperations after
      Postmastectomy Breast Reconstruction.
AB  - PURPOSE: Postmastectomy breast reconstruction (PMBR) aims to surgically restore a
      breast mound following mastectomy. However, additional surgical procedures after
      PMBR can lead to increased postsurgical morbidity and healthcare utilization. The
      primary purpose of our study was to determine the overall population-based
      reoperation rates following PMBR in Ontario, Canada. METHODS: We conducted a
      population-based retrospective cohort study that included women aged 18-65 years
      who underwent a prophylactic or therapeutic mastectomy with immediate or delayed
      PMBR between April 1, 2002 and March 31, 2008. Reoperations to the breast or
      donor site used for reconstruction were identified using the Ontario Health
      Insurance Plan billing codes submitted by general or plastic surgeons.
      Reoperations were categorized as anticipated, unanticipated major, unanticipated
      minor, or oncologic. Patients were followed from the date of their PMBR to March
      31, 2013, or death. RESULTS: Overall, 3972 women underwent PMBR between April 1,
      2002 and March 31, 2008. Among them, 3504 (88%) underwent at least one
      reoperation during an average follow-up of 5.1 years. The median number of
      procedures per patient was two (mean 2.4, range 0-26). One of ten patients had
      three or more unanticipated major reoperations during the follow-up period.
      CONCLUSIONS: Our results provide the first long-term population-level data on the
      current state of PMBR reoperation rates. The results from this study will inform
      patient-physician surgical decision-making and provide quantitative expectations
      of morbidity related to PMBR.

PMID- 26202564
TI  - Increasing Use of Neoadjuvant Treatment for T1 and T2 HER2-Positive Tumors.
AB  - BACKGROUND: Use of targeted therapy for human epidermal growth factor receptor-2
      (HER2)-positive breast cancer has led to improvements in survival. Furthermore,
      neoadjuvant chemotherapy (NAC) with dual HER2 agents demonstrated improved
      pathological complete response (pCR) rates. With these data, and with US FDA
      approval in September 2013 of pertuzumab in the neoadjuvant setting, we
      hypothesized that the use of NAC for early-stage HER2-positive patients is
      increasing. METHODS: With Institutional Review Board approval, we reviewed 267
      patients with 268 clinical T1 and T2 HER2-positive tumors treated from October
      2008 to September 2014. We compared treatment in the early (October 2008
      September 2013) to recent (October 2013-September 2014) periods. Statistical
      analysis was performed using Chi square tests. RESULTS: Mean patient age was 59
      years. Clinical T stage included 6 (2%) T1mic, 11 (4%) T1a, 41 (15%) T1b, 95
      (35%) T1c, and 115 (43%) T2. Targeted therapy included combinations of
      trastuzumab, lapatinib, pertuzumab, and neratinib. NAC use increased from 53/219
      (24.2%) in the early group to 19/49 (38.8%) in the recent group (p = 0.04). Forty
      two percent (8/19) of patients in the recent group received neoadjuvant
      pertuzumab versus 0/53 in the early group (p < 0.0001). More clinically node
      negative (cN0) patients received NAC in the recent (12/41, 29.3%) versus early
      (20/167, 12.0%) period (p = 0.01). For T1 tumors, the use of NAC more than
      doubled between the two time periods (5.6-17.2%; p = 0.06), while NAC use
      increased from 48 to 70% for T2 tumors (p = 0.08). The overall pCR rate after NAC
      was 48.6% (35/72). CONCLUSIONS: NAC for HER2-positive breast cancer patients is
      increasing. Most striking was a substantial increase in NAC for patients with T1
      tumors and cN0 disease.

PMID- 26202565
TI  - What is a Breast Surgeon Worth? A Salary Survey of the American Society of Breast
      Surgeons.
AB  - BACKGROUND: Breast surgeons negotiating employment agreements have little
      national data available. To reduce this knowledge gap, the Education Committee of
      the American Society of Breast Surgeons conducted a survey of its membership.
      METHODS: In 2014, survey questionnaires were sent to society members. Data
      collected included gender, type of practice, percentage devoted to breast
      surgery, volume of breast cases, work relative value units, location, benefits,
      and salary. Descriptive statistics were provided, and a multinomial logistic
      regression was performed to analyze the impact of various potential factors on
      salary. RESULTS: Of the 2784 members, a total of 843 observations were included.
      Overall, 54% of respondents dedicated 100 % of their practice to breast surgery,
      64.3% were female, and 40% were fellowship-trained in breast surgery or surgical
      oncology. The mean income in 2013 was $330.7k. Results from a multinomial model
      showed gender (p < 0.0001), ownership (p = 0.03), years of practice (p < 0.0001),
      practice setting (p < 0.0001), practice volume (p < 0.0001), and geographic
      location (p = 0.05) were statistically significant. After adjusting for other
      variables, the expected income was higher for males ($378k vs. $310k). The lowest
      expected income by practice setting was in solo private practice ($249.2k),
      followed by single-specialty private practice ($285.8k), and academic ($308.5k),
      with the highest being multispecialty group private practice ($346.6k) and
      hospital-employed practice ($368.0k). Practice 100% dedicated to breast surgery
      had a lower than expected income ($326k vs. $343k). CONCLUSIONS: Salary-specific
      data for breast surgeons are limited, and differences in salary were seen across
      geographic regions, type of practice, and gender. This type of breast-surgeon
      specific data may be helpful in ensuring equitable compensation.

PMID- 26202566
TI  - Single Institution Experience with Lymphatic Microsurgical Preventive Healing
      Approach (LYMPHA) for the Primary Prevention of Lymphedema.
AB  - BACKGROUND: As many as 40 % of breast cancer patients undergoing axillary lymph
      node dissection (ALND) and radiotherapy develop lymphedema. We report our
      experience performing lymphatic-venous anastomosis using the lymphatic
      microsurgical preventive healing approach (LYMPHA) at the time of ALND. This
      technique was described by Boccardo, Campisi in 2009. METHODS: LYMPHA was offered
      to node-positive women with breast cancer requiring ALND. Afferent lymphatic
      vessels, identified by injection of blue dye in the ipsilateral arm, were sutured
      into a branch of the axillary vein distal to a competent valve. Follow-up was
      with pre- and postoperative lymphoscintigraphy, arm measurements, and (L-Dex(r))
      bioimpedance spectroscopy. RESULTS: Over 26 months, 37 women underwent attempted
      LYMPHA, with successful completion in 27. Unsuccessful attempts were due to lack
      of a suitable vein (n = 3) and lymphatic (n = 5) or extensive axillary disease (n
      = 1). There were no LYMPHA-related complications. Mean follow-up time was 6
      months (range 3-24 months). Among completed patients, 10 (37%) had a body mass
      index of >=30 kg/m(2) (mean 27.9 +/- 6.8 kg/m(2), range 17.4-47.6 kg/m(2)), and
      17 (63%) received axillary radiotherapy. Excluding two patients with preoperative
      lymphedema and those with less than 3-month follow-up, the lymphedema rate was 3
      (12.5%) of 24 in successfully completed and 4 (50 %) of 8 in unsuccessfully
      treated patients. CONCLUSIONS: Our transient lymphedema rate in this high-risk
      cohort of patients was 12.5%. Early data show that LYMPHA is feasible, safe, and
      effective for the primary prevention of breast cancer-related lymphedema.

PMID- 26202567
TI  - Expanded Indications and Improved Outcomes for Nipple-Sparing Mastectomy Over
      Time.
AB  - BACKGROUND: Demand for nipple-sparing mastectomy (NSM) has increased. The
      authors' initial NSM guidelines included risk reduction and cancers 2 cm or
      smaller located more than 2 cm from the nipple. The relative contraindications
      included obesity, large and/or ptotic breasts, and prior radiation. This study
      aimed to evaluate changes over time in NSM indications, surgical approach, and
      early outcomes. METHODS: After institutional review board approval, the study
      identified 354 patients scheduled for 588 NSMs, 341 (96%) of whom underwent 566
      NSMs. Changes across time [early (2009-2010), mid (2011-2012), and recent (2013
      6/2014)] were assessed using tests for linear trend. RESULTS: For patients
      undergoing reconstruction, NSMs increased from 24% (early) to 40% (recent) (p =
      0.004). Among the NSM patients, average body mass index, proportion with bra cup
      sizes of C or larger, and prior radiation increased significantly over time.
      Performance of NSM for tumors 2 cm or less from the nipple increased from 5 to
      18%, and after neoadjuvant therapy, from 8 to 21.5% (p = 0.02). Use of
      inframammary, radial, and reduction-type incisions increased over time, together
      with intraoperative laser angiography (both p < 0.0001). Concomitantly, the
      overall complication rate, complications requiring treatment, and postoperative
      nipple loss decreased. During a median follow-up period of 19 months, five
      locoregional recurrences (LRR) were observed, for an estimated 2-year LRR rate of
      1.7% [95% confidence interval (CI), 0-3.9%]. CONCLUSIONS: Over time, the
      indications for NSM expanded in terms of patient characteristics, tumor stage,
      and prior therapy, whereas the complication rates decreased. Excellent short-term
      outcomes suggest that NSM is a reasonable approach for many risk-reduction and
      cancer patients without disease in the nipple-areolar complex. Further study is
      needed to assess long-term aesthetics, patient satisfaction, and oncologic
      safety.

PMID- 26202568
TI  - Computing a Synthetic Chronic Psychosocial Stress Measurement in Multiple
      Datasets and its Application in the Replication of G * E Interactions of the EBF1
      Gene.
AB  - Chronic psychosocial stress adversely affects health and is associated with the
      development of disease [Williams, 2008]. Systematic epidemiological and genetic
      studies are needed to uncover genetic variants that interact with stress to
      modify metabolic responses across the life cycle that are the proximal
      contributors to the development of cardiovascular disease and precipitation of
      acute clinical events. Among the central challenges in the field are to perform
      and replicate gene-by-environment (G * E) studies. The challenge of measurement
      of individual experience of psychosocial stress is magnified in this context.
      Although many research datasets exist that contain genotyping and disease-related
      data, measures of psychosocial stress are often either absent or vary
      substantially across studies. In this paper, we provide an algorithm to create a
      synthetic measure of chronic psychosocial stress across multiple datasets,
      applying a consistent criterion that uses proxy indicators of stress components.
      We validated the computed scores of chronic psychosocial stress by observing
      moderately strong and significant correlations with the self-rated chronic
      psychosocial stress in the Multi-Ethnic Study of Atherosclerosis Cohort (Rho =
      0.23, P < 0.0001) and with the measures of depressive symptoms in five datasets
      (Rho = 0.15-0.42, Ps = 0.005 to <0.0001) and by comparing the distributions of
      the self-rated and computed measures. Finally, we demonstrate the utility of this
      computed chronic psychosocial stress variable by providing three additional
      replications of our previous finding of gene-by-stress interaction with central
      obesity traits [Singh et al., 2015].

PMID- 26202569
TI  - Protective effects of Notch1 signaling activation against high glucose-induced
      myocardial cell injury: Analysis of its mechanisms of action.
AB  - Notch1 plays an important role in cardiomyocyte apoptosis and cardiac fibrosis.
      However, the effects of Notch1 on diabetic cardiomyopathy (DCM) and its
      mechanisms of action remain unclear. In the present study, we sought to
      investigate the role of Notch1 in, and its effects on high glucose (HG)-induced
      myocardial cell apoptosis and myocardial fibrosis. H9c2 cells exposed to HG were
      used to establish an in vitro model of myocardial injury. The H9c2 cells were
      cultured with normal glucose (NG; 5.5 mmol/L- NG), and were then epxosed to HG
      (33 mmol/L- HG), a gamma-secretase inhibitor (DAPT), and were transfected with a
      lentiviral vector containing the Notch1 intracellular domain (N1ICD; lentivirus
      N1ICD). At 72 h following exposure to HG, DAPT or transfection with lentivirus
      N1ICD, myocardial cell viability was assessed using a Cell Counting kit-8 (CCK-8)
      assay. Cell apoptosis was measured using Annexin V/propidium iodide (PI) double
      staining and flow cytometry. The mRNA expression levels of hairy/enhancer of
      split-1 (Hes-1) and hairy/enhancer-of-split related with YRPW motif-1 (Hey-1)
      were measured by quantitative PCR (qPCR), while the protein expression of N1ICD,
      Bax, Bcl-2, transforming growth factor-beta1 (TGF-beta1) and connective tissue
      growth factor (CTGF), and the levels of phosphorylated (p-)AKT, total (t-)AKT, p
      phosphoinositide 3-kinase (PI3K) and t-AKT were measured by western blot
      analysis. Our results revealed that exposure to HG induced apoptosis and
      upregulated TGF-beta1 and CTGF expression in the H9c2 cardiomyocytes.
      Furthermore, the Notch1 and PI3K/AKT signaling pathways were activated following
      transfection with lentivirus-N1ICD, and this activation enhanced myocardial cell
      viability, prevented cardiomyocyte apoptosis and decreased TGF-beta1 and CTGF
      expression. On the whole, our data demonstrate that the overexpression of Notch1
      prevents HG-induced cardiomyocyte apoptosis and decreases CTGF expression in H9c2
      cells exposed to HG. Thus, Notch1 may be used to prevent the development of DCM
      and to inhibit cardiac fibrosis. The findings of our study may prove to be of use
      in the development of novel therapeutic strategies for DCM.

PMID- 26202570
TI  - Overview of the Cancer Genetics and Pathway Curation tasks of BioNLP Shared Task
      2013.
AB  - BACKGROUND: Since their introduction in 2009, the BioNLP Shared Task events have
      been instrumental in advancing the development of methods and resources for the
      automatic extraction of information from the biomedical literature. In this
      paper, we present the Cancer Genetics (CG) and Pathway Curation (PC) tasks, two
      event extraction tasks introduced in the BioNLP Shared Task 2013. The CG task
      focuses on cancer, emphasizing the extraction of physiological and pathological
      processes at various levels of biological organization, and the PC task targets
      reactions relevant to the development of biomolecular pathway models, defining
      its extraction targets on the basis of established pathway representations and
      ontologies. RESULTS: Six groups participated in the CG task and two groups in the
      PC task, together applying a wide range of extraction approaches including both
      established state-of-the-art systems and newly introduced extraction methods. The
      best-performing systems achieved F-scores of 55% on the CG task and 53% on the PC
      task, demonstrating a level of performance comparable to the best results
      achieved in similar previously proposed tasks. CONCLUSIONS: The results indicate
      that existing event extraction technology can generalize to meet the novel
      challenges represented by the CG and PC task settings, suggesting that extraction
      methods are capable of supporting the construction of knowledge bases on the
      molecular mechanisms of cancer and the curation of biomolecular pathway models.
      The CG and PC tasks continue as open challenges for all interested parties, with
      data, tools and resources available from the shared task homepage.

PMID- 26202571
TI  - Life satisfaction and status among adolescent law offenders.
AB  - BACKGROUND: Life satisfaction among young offenders may be affected by the
      subjective experience of their social status and by the feeling of being a
      'loser' compared with others, but it is not clear what variables affect such
      experiences in this group. AIMS: To examine relationships of type of sentence
      (prison or probation) and of gender with subjective social status, sense of
      defeat and life satisfaction among young offenders. METHODS: One hundred and five
      participants were randomly selected from a cohort of young offenders, stratifying
      for sentence type and for gender. They were interviewed by trained and
      experienced interviewers. RESULTS: Young people in a correctional facility
      experienced lower life satisfaction and greater sense of defeat than those on
      probation. Independently of judicial measure, low life satisfaction was
      correlated with sense of defeat among young men but not young women, whereas
      among young women, but not young men, low life satisfaction was associated with
      low subjective status. CONCLUSIONS AND IMPLICATIONS: Our findings of a
      correlation between sentence type and life satisfaction needs new, longitudinal
      research to determine the direction of this relationship. Whether low life
      satisfaction is predictive of a custodial disposal for young offenders or such a
      sentence lowers life satisfaction, those trying to supervise or help these young
      people may need to take account of it. Further, our findings suggest that young
      male and young female offenders should perhaps be treated in different ways to
      improve their sense of satisfaction with life, which may, in turn, reduce their
      risk of reoffending.

PMID- 26202572
TI  - Interleukin-26: An Emerging Player in Host Defense and Inflammation.
AB  - The production of interleukin (IL)-26 was initially attributed to T cells, and in
      particular to Th17 cells. However, more recent findings indicate IL-26 production
      in natural killer (NK) cells, macrophages and fibroblast-like cells as well. It
      is known that IL-26 binds to the IL-20R1/IL-10R2 receptor complex on certain
      target cells, where it causes specific intracellular signaling and the secretion
      of IL-1beta, IL-8 and TNF-alpha. In line with this type of proinflammatory role,
      IL-26 also increases chemotaxis of human neutrophils. Interestingly, high levels
      of IL-26 are present even in normal human airways, and endotoxin exposure further
      enhances these levels; this indicates involvement in antibacterial host defense.
      Studies on acute inflammatory disorders are few but there are studies showing the
      involvement of IL-26 in rheumatoid arthritis and inflammatory bowel disease. In
      conclusion, IL-26 is emerging as a potentially important player in host defense
      and may also be a pathogenic factor in the chronic inflammatory disorders of
      humans. 

PMID- 26202573
TI  - Impact of quality indicators on adherence to National and European guidelines for
      renal cell carcinoma.
AB  - OBJECTIVE: The aim of this population-based study was to evaluate the impact of
      quality indicators on the adherence to guidelines for renal cell carcinoma (RCC).
      MATERIAL AND METHODS: Since 2005, virtually all patients with newly diagnosed RCC
      in Sweden have been registered in the National Swedish Kidney Cancer Register
      (NSKCR). The register contains information on histopathology, nuclear grade,
      clinical stage, preoperative work-up, treatment, recurrence and survival. In
      addition, a number of quality indicators have been measured in the register
      aiming to increase the quality of care. The quality indicators are: the coverage
      of the register, histology reports, preoperative chest computed tomography (CT),
      partial nephrectomy, laparoscopic surgery, centralization to high-volume
      hospitals and waiting times. RESULTS: A total of 8556 patients with diagnosed RCC
      were registered from 2005 to 2013 (99% coverage). In 2013, 99% of the
      histopathology reports were standardized. The number of patients with
      preoperatively chest CT increased from 59% in 2005 to 89% in 2013. The proportion
      of patients with RCC T1aN0M0 who underwent partial nephrectomy increased from 22%
      in 2005 to 56% in 2013. Similarly, laparoscopic radical nephrectomies increased
      from 6% in 2005 to 24% in 2013. The median tumour size at detection decreased
      from 60 mm in 2005 to 55 mm in 2013. The proportion of patients who were
      incidentally detected increased from 43% in 2005 to 55% in 2013. CONCLUSIONS: The
      data show an improved adherence to the guidelines for RCC as measured by quality
      indicators and a steady process of earlier detection of patients with RCC.

PMID- 26202574
TI  - Satellite DNA in Plants: More than Just Rubbish.
AB  - For decades, satellite DNAs have been the hidden part of genomes. Initially
      considered as junk DNA, there is currently an increasing appreciation of the
      functional significance of satellite DNA repeats and of their sequences.
      Satellite DNA families accumulate in the heterochromatin in different parts of
      the eukaryotic chromosomes, mainly in pericentromeric and subtelomeric regions,
      but they also span the functional centromere. Tandem repeat sequences may spread
      from subtelomeric to interstitial loci, leading to the formation of chromosome
      specific loci or to the accumulation in equilocal sites in different chromosomes.
      They also appear as the main components of the heterochromatin in the sex
      specific region of sex chromosomes. Satellite DNA, required for chromosome
      organization, also plays a role in pairing and segregation. Some satellite
      repeats are transcribed and can participate in the formation and maintenance of
      heterochromatin structure and in the modulation of gene expression. In addition
      to the identification of the different satellite DNA families, their
      characteristics and location, we are interested in determining their impact on
      the genomes, by identifying the mechanisms leading to their appearance and
      amplification as well as in understanding how they change over time, the factors
      affecting these changes, and the influence exerted by the evolutionary history of
      the organisms. On the other hand, satellite DNA sequences are rapidly evolving
      sequences that may cause reproductive barriers between organisms and promote
      speciation. The accumulation of experimental data collected in recent years and
      the emergence of new approaches based on next-generation sequencing and high
      throughput genome analysis are opening new perspectives that are changing our
      understanding of satellite DNA. This review examines recent data to provide a
      timely update on the overall information gathered about this part of the genome,
      focusing on the advances in the knowledge of its origin, its evolution, and its
      potential functional roles. 

PMID- 26202575
TI  - Genome-wide association study of IgA nephropathy using 23 465 microsatellite
      markers in a Japanese population.
AB  - Immunoglobulin A nephropathy (IgAN) is the most common form of primary
      glomerulonephritis in many parts of the world. Although previous genome-wide
      association studies (GWAS) identified the major susceptibility loci for IgAN, the
      causal genes currently remain unknown. We performed a GWAS using 23 465
      microsatellite (MS) markers to identify genes related to IgAN in a Japanese
      population. A pooled sample analysis was conducted in three-stage screenings of
      three independent case-control populations, and after the final step of
      individual typing, 11 markers survived. Of these, we focused on two regions on
      6p21 and 12q21 because they (i) showed the strongest relationship with IgAN, and
      (ii) appeared to be highly relevant to IgAN in view of several previous studies.
      These regions contained the HLA, TSPAN8 and PTPRR genes. This study on GWAS,
      using >20 000 MS markers, provides a new approach regarding susceptible genes for
      IgAN for investigators seeking new tools for the prevention and treatment of
      IgAN. 

PMID- 26202576
TI  - Distribution of HLA haplotypes across Japanese Archipelago: similarity,
      difference and admixture.
AB  - The human leukocyte antigen (HLA) region is the most polymorphic region in the
      human genome. The polymorphic nature of the HLA region is thought to have been
      shaped from balancing selection. The complex migration events during the Out-of
      Africa expansion have influenced geographic patterns of HLA allele frequencies
      and diversities across present-day human populations. Differences in the HLA
      allele frequency may contribute geographic differences in the susceptibility to
      many diseases, such as infectious, autoimmune and metabolic diseases. Here we
      briefly reviewed characteristics of frequency distribution of HLA alleles and
      haplotypes in Japanese population. A large part of HLA alleles and haplotypes
      that are common in Japanese are shared with neighboring Asian populations. The
      differentiations in HLA alleles and haplotypes across Japanese regional
      populations may provide clues to model for peopling of Japanese Archipelago and
      for design of genetic association studies. Finally, we introduce recent topics
      that new HLA alleles derived from ancient admixtures with Neanderthals and
      Denisovans are thought to have played an important role in the adaptation of
      modern humans to local pathogens during Out-of-Africa expansion. 

PMID- 26202578
TI  - Depression and diabetes distress.

PMID- 26202577
TI  - Elucidating the mechanisms of transcription regulation during heart development
      by next-generation sequencing.
AB  - Dysregulation of transcription is associated with the pathogenesis of
      cardiovascular diseases, including congenital heart diseases and heart failure.
      However, it remains unclear how transcription factors regulate transcription in
      the heart and which genes are associated with cardiovascular diseases in humans.
      Development of genome-wide analyses using next-generation sequencers provides
      powerful methods to determine how these transcription factors and chromatin
      regulators control gene expressions and to identify causative genes in
      cardiovascular diseases. These technologies have revealed that transcription
      during heart development is elaborately regulated by multiple cardiac
      transcription factors. In this review, we discuss the recent progress toward
      understanding the molecular mechanisms of how transcriptional dysregulation leads
      to cardiovascular diseases. 

PMID- 26202579
TI  - Thermal plasticity of growth and development varies adaptively among alternative
      developmental pathways.
AB  - Polyphenism, the expression of discrete alternative phenotypes, is often a
      consequence of a developmental switch. Physiological changes induced by a
      developmental switch potentially affect reaction norms, but the evolution and
      existence of alternative reaction norms remains poorly understood. Here, we
      demonstrate that, in the butterfly Pieris napi (Lepidoptera: Pieridae), thermal
      reaction norms of several life history traits vary adaptively among switch
      induced alternative developmental pathways of diapause and direct development.
      The switch was affected both by photoperiod and temperature, ambient temperature
      during late development having the potential to override earlier photoperiodic
      cues. Directly developing larvae had higher development and growth rates than
      diapausing ones across the studied thermal gradient. Reaction norm shapes also
      differed between the alternative developmental pathways, indicating pathway
      specific selection on thermal sensitivity. Relative mass increments decreased
      linearly with increasing temperature and were higher under direct development
      than diapause. Contrary to predictions, population phenology did not explain
      trait variation or thermal sensitivity, but our experimental design probably
      lacks power for finding subtle phenology effects. We demonstrate adaptive
      differentiation in thermal reaction norms among alternative phenotypes, and
      suggest that the consequences of an environmentally dependent developmental
      switch primarily drive the evolution of alternative thermal reaction norms in P.
      napi. 

PMID- 26202580
TI  - Atomic-scale mapping of electronic structures across heterointerfaces by cross
      sectional scanning tunneling microscopy.
AB  - Interfacial science has received much attention recently based on the development
      of state-of-the-art analytical tools that can create and manipulate the charge,
      spin, orbital, and lattice degrees of freedom at interfaces. Motivated by the
      importance of nanoscale interfacial science that governs device operation, we
      present a technique to probe the electronic characteristics of heterointerfaces
      with atomic resolution. In this work, the interfacial characteristics of
      heteroepitaxial structures are investigated and the fundamental mechanisms that
      pertain in these systems are elucidated through cross-sectional scanning
      tunneling microscopy (XSTM). The XSTM technique is employed here to directly
      observe epitaxial interfacial structures and probe local electronic properties
      with atomic-level capability. Scanning tunneling microscopy and spectroscopy
      experiments with atomic precision provide insight into the origin and spatial
      distribution of electronic properties across heterointerfaces. The first part of
      this report provides a brief description of the cleavage technique and
      spectroscopy analysis in XSTM measurements. The second part addresses interfacial
      electronic structures of several model heterostructures in current condensed
      matter research using XSTM. Topics to be discussed include high-kappa's/III-V's
      semiconductors, polymer heterojunctions, and complex oxide heterostructures,
      which are all material systems whose investigation using this technique is
      expected to benefit the research community. Finally, practical aspects and
      perspectives of using XSTM in interface science are presented. 

PMID- 26202582
TI  - Sub-optimal responders following controlled ovarian stimulation: an overlooked
      group?
AB  - Individualization of IVF treatment and tailored stimulation based on predicted
      ovarian response may maximize treatment success and minimize the risks following
      IVF. Whilst there has been a consensus in defining poor ovarian response and an
      attempt to elucidate the threshold for excessive ovarian response based on the
      number of oocytes retrieved following ovarian stimulation, no systematic effort
      has been made in order to refine the oocyte yield thresholds for a normal
      responder. In this opinion article we discuss the evidence behind the oocyte
      number thresholds for the ovarian response categories and present the rationale
      and merits in recognizing a new, overlooked, ovarian response group: The sub
      optimal ovarian responders. 

PMID- 26202581
TI  - Development of Protective Immunity against Inactivated Iranian Isolate of Foot
      and-Mouth Disease Virus Type O/IRN/2007 Using Gamma Ray-Irradiated Vaccine on
      BALB/c Mice and Guinea Pigs.
AB  - OBJECTIVES: Foot-and-mouth disease virus (FMDV) causes a highly contagious
      disease in cloven-hoofed animals and is the most damaging disease of livestock
      worldwide, leading to great economic losses. The aim of this research was the
      inactivation of FMDV type O/IRN/1/2007 to produce a gamma ray-irradiated (GRI)
      vaccine in order to immunize mice and guinea pigs. METHODS: In this research, the
      Iranian isolated FMDV type O/IRN/1/2007 was irradiated by gamma ray to prepare an
      inactivated whole virus antigen and formulated as a GRI vaccine with unaltered
      antigenic characteristics. Immune responses against this vaccine were evaluated
      on mice and guinea pigs. RESULTS: The comparison of the immune responses between
      the GRI vaccine and conventional vaccine did not show any significant difference
      in neutralizing antibody titer, memory spleen T lymphocytes or IFN-gamma, IL-4,
      IL-2 and IL-10 concentrations (p > 0.05). In contrast, there were significant
      differences in all of the evaluated immune factors between the two vaccinated
      groups of mice and negative control mice (p < 0.05). The protective dose 50 for
      the conventional and GRI vaccines obtained were 6.28 and 7.07, respectively,
      which indicated the high potency of both vaccines. CONCLUSION: GRI vaccine is
      suitable for both routine vaccination and control of FMDV in emergency outbreaks.

PMID- 26202583
TI  - The sub-optimal response to controlled ovarian stimulation: manageable or
      inevitable?

PMID- 26202584
TI  - Stability-Indicating HPTLC Method for Simultaneous Estimation of Flurbiprofen and
      Chloramphenicol in Ophthalmic Solution.
AB  - A specific, accurate and reproducible stability-indicating high performance thin
      layer chromatography (HPTLC) method was developed for the estimation of
      flurbiprofen and chloramphenicol in the presence of their degradation products.
      Degradation studies of both the drugs were carried out in acidic, alkaline,
      neutral, oxidative, photolytic and thermal stress conditions. Separation was
      performed on thin layer chromatography plate precoated with silica gel 60 F254
      using ethyl acetate : n-hexane : methanol : tri-ethyl amine (5 : 4 : 2 : 0.5,
      v/v/v/v). Spots at retention factor 0.29 and 0.62 were recognized as flurbiprofen
      and chloramphenicol, respectively, and were quantified through densitometric
      measurements at wavelength 267 nm. Method was found to be linear over the
      concentration range 12-60 ng/spot with correlation coefficient of 0.9997 for
      flurbiprofen and 200-1,000 ng/spot with correlation coefficient of 0.9977 for
      chloramphenicol. The proposed method was applied to the estimation of
      flurbiprofen and chloramphenicol in commercial ophthalmic formulation. The
      developed HPTLC method can be applied for routine analysis of flurbiprofen and
      chloramphenicol in the presence of their degradation products in their individual
      as well as combined pharmaceutical formulations. 

PMID- 26202585
TI  - A New UPLC Approach for the Simultaneous Quantitative Estimation of Four
      Compounds in a Cough Syrup Formulation.
AB  - A new ultra-performance liquid chromatographic (UPLC) method was developed for
      the simultaneous estimation of potassium guaiacolsulfonate (PGS), guaifenesin
      (GUA), diphenhydramine HCl (DIP) and carbepentane citrate (CAR) in a commercial
      cough syrup. The chromatographic separation of four compounds PGS, GUA, DIP and
      CAR was performed on a BEH phenyl column (100 * 2.1 mm, 1.7 um i.d.) using a
      mobile phase consisting of acetonitrile and 0.1 M HCl (50 : 50, v/v). In
      addition, the optimized conditions of the chromatographic analysis were found
      with the flow rate of 0.38 mL/min, the column temperature of 30 degrees C and the
      injection volume of 1.2 uL with the photodiode array detection of 220 nm.
      Calibration curves in the concentration ranges of 10-98 ug/mL for PGS, 5-80 ug/mL
      for GUA, 5-25 ug/mL for DIP and CAR were computed by the regression of the
      analyte concentration on the chromatographic peak area. The newly developed UPLC
      method was validated by analyzing the quaternary mixtures of the related
      compounds, intraday and interday experiment and standard addition samples. After
      method validation, the proposed UPLC approach was successfully applied for the
      analysis of the commercial syrup formulation containing PGS, GUA, DIP and CAR
      compounds. 

PMID- 26202586
TI  - Virtual screening of a milk peptide database for the identification of food
      derived antimicrobial peptides.
AB  - SCOPE: Milk provides a wide range of bioactive substances, such as antimicrobial
      peptides and proteins. Our study aimed to identify novel antimicrobial peptides
      naturally present in milk. METHODS AND RESULTS: The components of an endogenous
      bovine milk peptide database were virtually screened for charge, amphipathy, and
      predicted secondary structure. Thus, 23 of 248 screened peptides were identified
      as candidates for antimicrobial effects. After commercial synthesis, their
      antimicrobial activities were determined against Escherichia coli NEB5alpha, E.
      coli ATCC25922, and Bacillus subtilis ATCC6051. In the tested concentration range
      (<2 mM), bacteriostatic activity of 14 peptides was detected including nine
      peptides inhibiting both Gram-positive and Gram-negative bacteria. The most
      effective fragment was TKLTEEEKNRLNFLKKISQRYQKFAlphaLPQYLK corresponding to
      alphaS2 -casein151-181 , with minimum inhibitory concentration (MIC) of 4.0 MUM
      against B. subtilis ATCC6051, and minimum inhibitory concentrations of 16.2 MUM
      against both E. coli strains. Circular dichroism spectroscopy revealed
      conformational changes of most active peptides in a membrane-mimic environment,
      transitioning from an unordered to alpha-helical structure. CONCLUSION: Screening
      of food peptide databases by prediction tools is an efficient method to identify
      novel antimicrobial food-derived peptides. Milk-derived antimicrobial peptides
      may have potential use as functional food ingredients and help to understand the
      molecular mechanisms of anti-infective milk effects.

PMID- 26202587
TI  - Synthesis and Biological Evaluations of 1,2-Diaryl Pyrroles as Analogues of
      Combretastatin A-4.
AB  - A series of novel 1,2-diaryl pyrroles as analogues of combretastatin A-4 (CA-4,
      1a) were synthesized and evaluated for their antitumour potential against three
      cancer cell lines. Most compounds exhibited growth inhibition against all of the
      cancer cell lines. Compound 7q not only exhibited prominent antitumour efficacy
      with IC50 values of 0.390 MUm in SGC-7901, 0.070 MUm in HT-1080 and 0.045 MUm in
      KB cell lines but also showed low activity with IC50 values of 30.08 MUm in
      normal L929 cell line. Moreover, compound 7q inhibited tubulin polymerization
      into microtubules and caused microtubule destabilization. A molecular docking
      study of 7q was performed to determine its binding mode at the colchicine site in
      the tubulin dimer. 

PMID- 26202588
TI  - Chromium inhibition and size-selected Au nanocluster catalysis for the solution
      growth of low-density ZnO nanowires.
AB  - The wet chemical synthesis of nanostructures has many crucial advantages over
      high-temperature methods, including simplicity, low-cost, and deposition on
      almost arbitrary substrates. Nevertheless, the density-controlled solution growth
      of nanowires still remains a challenge, especially at the low densities (e.g. 1
      to 10 nanowires/100 MUm(2)) required, as an example, for intracellular analyses.
      Here, we demonstrate the solution-growth of ZnO nanowires using a thin chromium
      film as a nucleation inhibitor and Au size-selected nanoclusters (SSNCs) as
      catalytic particles for which the density and, in contrast with previous reports,
      size can be accurately controlled. Our results also provide evidence that the
      enhanced ZnO hetero-nucleation is dominated by Au SSNCs catalysis rather than by
      layer adaptation. The proposed approach only uses low temperatures (<=70  degrees
      C) and is therefore suitable for any substrate, including printed circuit boards
      (PCBs) and the plastic substrates which are routinely used for cell cultures. As
      a proof-of-concept we report the density-controlled synthesis of ZnO nanowires on
      flexible PCBs, thus opening the way to assembling compact intracellular-analysis
      systems, including nanowires, electronics, and microfluidics, on a single
      substrate. 

PMID- 26202589
TI  - Rats' midsession reversal performance: the nature of the response.
AB  - The midsession reversal task involves a simple simultaneous discrimination that
      predictably reverses midway through a session. Under various conditions, pigeons
      generally both anticipate the reversal and perseverate once it has occurred,
      whereas rats tend to make very few of either kind of error. In the present
      research, we investigated the hypothesis that the difference in performance
      between rats and pigeons is related to the nature of the responses made. We
      hypothesized that rats could have been better at bridging the intertrial interval
      by keeping the relevant paw close to the lever while eating, whereas the pigeons
      had to remove their beak from the response key and insert it into the feeder,
      thus making it difficult to mediate the response last made. In the present
      experiment, in successive phases, rats were trained to leverpress or nose-poke on
      a 40-trial midsession reversal, an 80-trial midsession reversal, and a variable
      location reversal. The results showed that the leverpress group acquired the task
      faster than the nose-poke group, but that both groups reached comparable levels
      of performance. Thus, the difference in the natures of the responses cannot fully
      account for the differences in accuracy between rats and pigeons. Additionally,
      differences in the types of errors made by the two groups suggest that the nature
      of the response plays different roles in the performance of this task. 

PMID- 26202590
TI  - Acute Central Nervous System Complications in Pediatric Acute Lymphoblastic
      Leukemia.
AB  - BACKGROUND: The outcome of childhood acute lymphoblastic leukemia has improved
      because of intensive chemotherapy and supportive care. The frequency of adverse
      events has also increased, but the data related to acute central nervous system
      complications during acute lymphoblastic leukemia treatment are sparse. The
      purpose of this study is to evaluate these complications and to determine their
      long term outcome. PATIENTS AND METHODS: We retrospectively analyzed the hospital
      reports of 323 children with de novo acute lymphoblastic leukemia from a 13-year
      period for acute neurological complications. The central nervous system
      complications of leukemic involvement, peripheral neuropathy, and post-treatment
      late-onset encephalopathy, and neurocognitive defects were excluded. RESULTS:
      Twenty-three of 323 children (7.1%) suffered from central nervous system
      complications during acute lymphoblastic leukemia treatment. The majority of
      these complications (n = 13/23; 56.5%) developed during the induction period. The
      complications included posterior reversible encephalopathy (n = 6), fungal
      abscess (n = 5), cerebrovascular lesions (n = 5), syndrome of inappropriate
      secretion of antidiuretic hormone (n = 4), and methotrexate encephalopathy (n =
      3). Three of these 23 children (13%) died of central nervous system
      complications, one from an intracranial fungal abscess and the others from
      intracranial thrombosis. Seven of the survivors (n = 7/20; 35%) became epileptic
      and three of them had also developed mental and motor retardation. CONCLUSIONS:
      Acute central neurological complications are varied and require an urgent
      approach for proper diagnosis and treatment. Collaboration among the
      hematologist, radiologist, neurologist, microbiologist, and neurosurgeon is
      essential to prevent fatal outcome and serious morbidity.

PMID- 26202591
TI  - Robotic pancreaticoduodenectomy: comparison of complications and cost to the open
      approach.
AB  - BACKGROUND: Robotic pancreaticoduodenectomy (RP) has shown some advantages over
      open pancreaticoduodenectomy (OP) but no data has been published providing a cost
      comparison. METHODS: Retrospective analysis of all pancreaticoduodenectomies at a
      single quaternary cancer referral center was performed. Patient demographics,
      comorbidities, operative characteristics, complications, and charge data were
      recorded, and then compared using standard statistical methods. RESULTS: 71
      pancreaticoduodenectomies were performed: 22 RP and 49 OP. Patients undergoing OP
      had similar demographics, comorbidities, pathology, and oncologic characteristics
      as patients undergoing RP. While operative charges were higher for RP, once
      inpatient stay associated costs and follow-up costs were included, there was no
      difference in total costs between RP and OP. CONCLUSIONS: Patients undergoing RP
      have equivalent rates of R0 resection as OP, and benefit from decreased number of
      complications, surgical site infections, and length of stay in the intensive care
      unit. Once cost of complications and follow-up are incorporated, no significant
      difference between procedures exists. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26202592
TI  - Photolabile protection for amino acids: studies on the release from novel
      benzoquinolone cages.
AB  - The synthesis of a novel fused nitrogen heterocycle, benzoquinolone, for
      evaluation as a photocleavable protecting group is described for the first time
      by coupling to model amino acids (alanine, phenylalanine and glutamic acid).
      Conversion of the phenylalanine ester conjugate to the thionated derivative was
      accomplished by reaction with Lawesson's reagent. Photocleavage studies of the
      carbonyl and thiocarbonyl benzoquinolone conjugates in various solvents and at
      different wavelengths (300, 350 and 419 nm) showed that the most interesting
      result was obtained at 419 nm for the thioconjugate, revealing that the presence
      of the thiocarbonyl group clearly improved the photolysis rates, giving
      practicable irradiations times for the release of the amino acids (less than 1
      min).

PMID- 26202593
TI  - Economic burden of hepatitis C in Egypt: the future impact of highly effective
      therapies.
AB  - BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in Egypt is the
      highest in the world, yet the total economic burden has not been quantified.
      Improved understanding of costs and the impact of treatment strategies will
      provide for better allocation of resources to reduce HCV disease and economic
      burden. AIM: A modelling approach was used to quantify the current HCV-infected
      population, future disease progression and associated costs in Egypt. METHODS:
      Direct healthcare costs were calculated from a nationally representative hospital
      and a disability adjusted life year (DALY) template was used with monetary value
      assigned to lost life years. Three scenarios were considered: (i) Historical
      treatment scenario: 50% SVR; 65,000 treated annually, (ii) Current treatment
      scenario: 90% sustained virologic response (SVR); 65,000 treated annually, (iii)
      Increased treatment scenario: 90% SVR; 325,000 treated annually by 2018. RESULTS:
      Cumulative DALYs (2015-2030) under Scenario 1 were estimated at 7.88 million and
      cumulative costs estimated at $89.07 billion. Annual DALYs increased 16% during
      2015-2030 while annual costs more than doubled. Scenario 2 reduced cumulative
      DALYs and costs by 7% and 4%, respectively. Under Scenario 3, total costs
      declined 73% to $1047 million during 2015-2030. As compared to Scenario 1,
      cumulative DALYs and costs decreased 37% and 35%, respectively. CONCLUSIONS: This
      is the first estimate of the total economic burden of HCV in Egypt. Extraordinary
      measures are necessary to substantially reduce HCV disease and cost burden. With
      newer therapies, strategies to reduce disease burden are feasible and cost
      effective.

PMID- 26202594
TI  - Randomized, phase II, placebo-controlled trial of onartuzumab and/or bevacizumab
      in combination with weekly paclitaxel in patients with metastatic triple-negative
      breast cancer.
AB  - BACKGROUND: Increased hepatocyte growth factor/MET signaling is associated with
      an aggressive phenotype and poor prognosis in triple-negative breast cancer
      (TNBC). We evaluated the benefit of adding onartuzumab, a monoclonal anti-MET
      antibody, to paclitaxel with/without bevacizumab in patients with TNBC. PATIENTS
      AND METHODS: Women with metastatic TNBC were randomized to receive onartuzumab
      plus placebo plus weekly paclitaxel (OP; n = 60) or onartuzumab plus bevacizumab
      plus paclitaxel (OBP; n = 63) or placebo plus bevacizumab plus paclitaxel (BP; n
      = 62). The primary end point was progression-free survival (PFS); additional end
      points included overall survival (OS), objective response rate (ORR), and safety.
      This trial was hypothesis generating and did not have power to detect minimum
      clinically meaningful differences between treatment arms. RESULTS: There was no
      improvement in PFS with the addition of onartuzumab to BP [hazard ratio (HR),
      1.08; 95% confidence interval (CI) 0.69-1.70]; the risk of a PFS event was higher
      with OP than with BP (HR, 1.74; 95% CI 1.13-2.68). Most patients had MET-negative
      tumors (88%); PAM50 subtype analysis showed basal-like tumors in 68% of samples.
      ORR was higher in the bevacizumab arms (OBP: 42.2%; 95% CI 28.6-57.1; BP: 54.7%;
      95% CI 41.0-68.4) compared with OP (27.5%; 95% CI 15.9-40.6). Median OS was
      shorter with OBP (HR, 1.36; 95% CI 0.75-2.46) and OP (HR, 1.92; 95% CI 1.03
      3.59), than with BP. Peripheral edema was more frequent in the onartuzumab arms
      (OBP, 51.8%; OP, 58.6%) versus BP (17.7%). CONCLUSION: This study did not show a
      clinical benefit of the addition of onartuzumab to paclitaxel with/without
      bevacizumab in patients with predominantly MET-negative TNBC. CLINICALTRIALSGOV:
      NCT01186991.

PMID- 26202595
TI  - Randomized phase II study evaluating veliparib (ABT-888) with temozolomide in
      patients with metastatic melanoma.
AB  - BACKGROUND: Veliparib (ABT-888) is a potent, orally bioavailable, small-molecule
      inhibitor of the DNA repair enzymes poly ADP-ribose polymerase-1 and -2.
      Veliparib enhances the efficacy of temozolomide (TMZ) and other cytotoxic agents
      in preclinical tumor models. PATIENTS AND METHODS: In this multicenter, double
      blind trial, adults with unresectable stage III or IV metastatic melanoma were
      randomized 1:1:1 to TMZ plus veliparib 20 or 40 mg, or placebo twice daily.
      Efficacy end points included progression-free survival (PFS), overall survival
      (OS), and objective response rate (ORR). RESULTS: Patients (N = 346) were
      randomized between February 2009 and January 2010. Median [95% confidence
      interval (CI)] PFS was 3.7 (3.0-5.5), 3.6 (1.9-4.1), and 2 (1.9-3.7) months in
      the 20-mg, 40-mg, and placebo arms, respectively. Median (95% CI) OS was 10.8
      (9.0-13.1), 13.6 (11.4-15.9), and 12.9 (9.8-14.3) months, respectively; ORR was
      10.3%, 8.7%, and 7.0%. Exploratory analyses showed patients with low ERCC1
      expression had longer PFS when TMZ was combined with veliparib. Toxicities were
      as expected for TMZ. The frequencies of thrombocytopenia, neutropenia, and
      leukopenia were significantly increased in the veliparib groups. Grade 3 or 4
      adverse events, mainly hematologic toxicities, were seen in 55%, 63%, and 41% of
      patients in the 20-mg, 40-mg, and placebo arms, respectively. CONCLUSIONS: Median
      PFS with 20 and 40 mg veliparib almost doubled numerically compared with placebo,
      but the improvements did not reach statistical significance. OS was not increased
      with veliparib. Toxicities were similar to TMZ monotherapy, but with increased
      frequency.

PMID- 26202596
TI  - Sorafenib in patients with locally advanced and metastatic chordomas: a phase II
      trial of the French Sarcoma Group (GSF/GETO).
AB  - BACKGROUND: There is no consensual treatment of locally advanced or metastatic
      chordomas. PATIENTS AND METHODS: We conducted a multicenter, open-label,
      uncontrolled phase II trial of sorafenib (800 mg/day). The primary end point was
      the 9-month progression-free rate according to RECIST 1.1. All patients had
      documented progressive disease at the time of study entry. RESULTS: Twenty-seven
      patients were enrolled between May 2011 and January 2014. The median age was 64
      (range, 30-86) years. There were 17 men and 10 women. Twelve patients had been
      previously treated with chemotherapy and molecularly targeted agents. The maximum
      toxicity grade per patient was grade 3 in 21 cases (77.8%) and grade 4 in 4 cases
      (14.8%). Sorafenib provided an intent-to-treat best objective response of 1/27
      [3.7%; 95% confidence interval (CI) 0.1% to 19.0%], a 9-month progression-free
      rate of 73.0% (95% CI 46.1-88.0) and a 12-month overall survival rate of 86.5%
      (95% CI 55.8-96.5). Survival curves were similar in pretreated and not pretreated
      patients. DISCUSSION: Additional clinical trials further exploring sorafenib as a
      treatment of locally advanced or metastatic chordomas are warranted.

PMID- 26202598
TI  - Endoscopic retrieval of a proximally migrated pancreatic stent.

PMID- 26202597
TI  - Prospective study evaluating the relative sensitivity of 18F-NaF PET/CT for
      detecting skeletal metastases from renal cell carcinoma in comparison to
      multidetector CT and 99mTc-MDP bone scintigraphy, using an adaptive trial design.
AB  - BACKGROUND: The detection of occult bone metastases is a key factor in
      determining the management of patients with renal cell carcinoma (RCC),
      especially when curative surgery is considered. This prospective study assessed
      the sensitivity of (18)F-labelled sodium fluoride in conjunction with positron
      emission tomography/computed tomography ((18)F-NaF PET/CT) for detecting RCC bone
      metastases, compared with conventional imaging by bone scintigraphy or CT.
      PATIENTS AND METHODS: An adaptive two-stage trial design was utilized, which was
      stopped after the first stage due to statistical efficacy. Ten patients with
      stage IV RCC and bone metastases were imaged with (18)F-NaF PET/CT and (99m)Tc
      labelled methylene diphosphonate ((99m)Tc-MDP) bone scintigraphy including pelvic
      single photon emission computed tomography (SPECT). Images were reported
      independently by experienced radiologists and nuclear medicine physicians using a
      5-point scoring system. RESULTS: Seventy-seven lesions were diagnosed as
      malignant: 100% were identified by (18)F-NaF PET/CT, 46% by CT and 29% by bone
      scintigraphy/SPECT. Standard-of-care imaging with CT and bone scintigraphy
      identified 65% of the metastases reported by (18)F-NaF PET/CT. On an individual
      patient basis, (18)F-NaF PET/CT detected more RCC metastases than (99m)Tc-MDP
      bone scintigraphy/SPECT or CT alone (P = 0.007). The metabolic volumes, mean and
      maximum standardized uptake values (SUV mean and SUV max) of the malignant
      lesions were significantly greater than those of the benign lesions (P < 0.001).
      CONCLUSIONS: (18)F-NaF PET/CT is significantly more sensitive at detecting RCC
      skeletal metastases than conventional bone scintigraphy or CT. The detection of
      occult bone metastases could greatly alter patient management, particularly in
      the context when standard-of-care imaging is negative for skeletal metastases.

PMID- 26202599
TI  - Genetic variation in insulin-induced kinase signaling.
AB  - Individual differences in sensitivity to insulin contribute to disease
      susceptibility including diabetes and metabolic syndrome. Cellular responses to
      insulin are well studied. However, which steps in these response pathways differ
      across individuals remains largely unknown. Such knowledge is needed to guide
      more precise therapeutic interventions. Here, we studied insulin response and
      found extensive individual variation in the activation of key signaling factors,
      including ERK whose induction differs by more than 20-fold among our subjects.
      This variation in kinase activity is propagated to differences in downstream gene
      expression response to insulin. By genetic analysis, we identified cis-acting DNA
      variants that influence signaling response, which in turn affects downstream
      changes in gene expression and cellular phenotypes, such as protein translation
      and cell proliferation. These findings show that polymorphic differences in
      signal transduction contribute to individual variation in insulin response, and
      suggest kinase modulators as promising therapeutics for diseases characterized by
      insulin resistance. 

PMID- 26202600
TI  - Dynamic reorganization of neural activity in motor cortex during new sequence
      production.
AB  - Although previous studies have shown that primary motor cortex (M1) neurons are
      modulated during the performance of a sequence of movements, it is not known how
      this neural activity in the M1 reorganizes during new learning of sequence
      dependent motor skills. Here we trained monkeys to move to each of four spatial
      targets to produce multiple distinct sequences of movements in which the spatial
      organization of the targets determined uniquely the serial order of the
      movements. After the monkeys memorized the sequences, we changed one element of
      these over-practised sequences and the subjects were required to learn the new
      sequence through trial and error. When one element in an over-learned four
      element sequence was changed, the sequence-specific neural activity was totally
      disrupted, but relatively minor changes in the direction-specific activity were
      observed. The data suggest that sequential motor skills are represented within M1
      in the context of the complete sequential behavior rather than as a series of
      single consecutive movements; and sequence-specific neurons in the M1 are
      involved in new learning of sequence by using memorized knowledge to acquire
      complex motor skill efficiently. 

PMID- 26202602
TI  - A qualitative study of cancer survivors' responses to information on the long
      term and late effects of pelvic radiotherapy 1-11 years post treatment.
AB  - As more patients survive cancer for longer term, the long-term and late effects
      of treatments become increasingly important issues for cancer survivors and
      providing information to enable survivors to recognise and manage them becomes an
      increasingly pressing challenge for health care professionals. The aim of this
      study was to explore the experiences of cancer survivors regarding information
      given on potential long-term and late effects of pelvic radiotherapy. Semi
      structured interviews were conducted with 28 cancer survivors who had had
      radiotherapy to the pelvic area for a range of cancers 1-11 years previously.
      Participants were recruited using maximum variation sampling from a larger
      questionnaire survey of patients treated at one hospital. Interviews were
      recorded, transcribed and analysed using Framework. Participants recognised the
      value of information to reassure and to inform action but also its potentially
      undesirable effects to frighten or raise anxieties about future problems and its
      inherent limitations in meeting their wider needs. They identified the timing,
      amount of information and context in which it was given as of particular
      importance. Information based on personal experience was also valued. These
      findings highlight the importance of appropriate, individualised information
      during treatment, at hospital discharge and subsequently in primary care.

PMID- 26202601
TI  - Identification of a multi-cancer gene expression biomarker for cancer clinical
      outcomes using a network-based algorithm.
AB  - Cancer types are commonly classified by histopathology and more recently through
      molecular characteristics such as gene expression, mutations, copy number
      variations, and epigenetic alterations. These molecular characterizations have
      led to the proposal of prognostic biomarkers for many cancer types. Nevertheless,
      most of these biomarkers have been proposed for a specific cancer type or even
      specific subtypes. Although more challenging, it is useful to identify biomarkers
      that can be applied for multiple types of cancer. Here, we have used a network
      based exploration approach to identify a multi-cancer gene expression biomarker
      highly connected by ESR1, PRKACA, LRP1, JUN and SMAD2 that can be predictive of
      clinical outcome in 12 types of cancer from The Cancer Genome Atlas (TCGA)
      repository. The gene signature of this biomarker is highly supported by cancer
      literature, biological terms, and prognostic power in other cancer types.
      Additionally, the signature does not seem to be highly associated with specific
      mutations or copy number alterations. Comparisons with cancer-type specific and
      other multi-cancer biomarkers in TCGA and other datasets showed that the
      performance of the proposed multi-cancer biomarker is superior, making the
      proposed approach and multi-cancer biomarker potentially useful in research and
      clinical settings. 

PMID- 26202603
TI  - "Do-it-yourself in vitro vasculature that recapitulates in vivo geometries for
      investigating endothelial-blood cell interactions".
AB  - Investigating biophysical cellular interactions in the circulation currently
      requires choosing between in vivo models, which are difficult to interpret due in
      part to the hemodynamic and geometric complexities of the vasculature; or in
      vitro systems, which suffer from non-physiologic assumptions and/or require
      specialized microfabrication facilities and expertise. To bridge that gap, we
      developed an in vitro "do-it-yourself" perfusable vasculature model that
      recapitulates in vivo geometries, such as aneurysms, stenoses, and bifurcations,
      and supports endothelial cell culture. These inexpensive, disposable devices can
      be created rapidly (<2 hours) with high precision and repeatability, using
      standard off-the-shelf laboratory supplies. Using these "endothelialized"
      systems, we demonstrate that spatial variation in vascular cell adhesion molecule
      (VCAM-1) expression correlates with the wall shear stress patterns of vascular
      geometries. We further observe that the presence of endothelial cells in stenoses
      reduces platelet adhesion but increases sickle cell disease (SCD) red blood cell
      (RBC) adhesion in bifurcations. Overall, our method enables researchers from all
      disciplines to study cellular interactions in physiologically relevant, yet
      simple-to-make, in vitro vasculature models. 

PMID- 26202605
TI  - Impact of paleoclimate on the distribution of microbial communities in the
      subsurface sediment of the Dead Sea.
AB  - A long sedimentary core has been recently retrieved from the Dead Sea Basin (DSB)
      within the framework of the ICDP-sponsored Dead Sea Deep Drilling Project.
      Contrasting climatic intervals were evident by distinctive lithological facies
      such as laminated aragonitic muds and evaporites. A geomicrobiological
      investigation was conducted in representative sediments of this core. To identify
      the microbial assemblages present in the sediments and their evolution with
      changing depositional environments through time, the diversity of the 16S rRNA
      gene was analyzed in gypsum, aragonitic laminae, and halite samples. The
      subsurface microbial community was largely dominated by the Euryarchaeota phylum
      (Archaea). Within the latter, Halobacteriaceae members were ubiquitous, probably
      favored by their 'high salt-in' osmotic adaptation which also makes them one of
      the rare inhabitants of the modern Dead Sea. Bacterial community members were
      scarce, emphasizing that the 'low salt-in' strategy is less suitable in this
      environment. Substantial differences in assemblages are observed between
      aragonitic sediments and gypsum-halite ones, independently of the depth and
      salinity. The aragonite sample, deposited during humid periods when the lake was
      stratified, consists mostly of the archaeal MSBL1 and bacterial KB1 Candidate
      Divisions. This consortium probably relies on compatible solutes supplied from
      the lake by halotolerant species present in these more favorable periods. In
      contrast, members of the Halobacteriaceae were the sole habitants of the gypsum
      halite sediments which result from a holomictic lake. Although the biomass is
      low, these variations in the observed subsurface microbial populations appear to
      be controlled by biological conditions in the water column at the time of
      sedimentation, and subsequently by the presence or absence of stratification and
      dilution in the lake. As the latter are controlled by climatic changes, our data
      suggest a relationship between local lacustrine subsurface microbial assemblages
      and large-scale climatic variations over the Dead Sea Basin. 

PMID- 26202604
TI  - Two-step statistical optimization for cold active beta-glucosidase production
      from Pseudomonas lutea BG8 and its application for improving saccharification of
      paddy straw.
AB  - beta-Glucosidase is an essential part of cellulase enzyme system for efficient
      and complete hydrolysis of biomass. Psychrotolerant Pseudomonas lutea BG8
      produced beta-glucosidase with lower temperature optima and hence can play
      important role in bringing down the energy requirement for bioethanol production.
      To enhance beta-glucosidase production, two statistical tools: Taguchi and Box
      Behnken designs were applied to reveal the most influential factors and their
      respective concentration for maximum production of beta-glucosidase under
      submerged fermentation. The optimal medium composition for maximum beta
      glucosidase production were 2.99% (w/v) bagasse, 0.33% (w/v) yeast extract, 0.38%
      (w/v) Triton X-100, 0.39% (w/v) NaNO3 , and pH 8.0 at temperature 30  degrees C.
      Under optimized conditions, beta-glucosidase production increased up to 9.12-fold
      (17.52 +/- 0.24 IU/g) in shake flask. Large-scale production in 7-L stirred tank
      bioreactor resulted in higher beta-glucosidase production (23.29 +/- 0.23 IU/g)
      within 80 H of incubation, which was 1.34-fold higher than shake flask studies.
      Commercial cellulase (Celluclast(r) 1.5L) when supplemented with this crude beta
      glucosidase resulted in improved sugar release (548.4 +/- 2.76 mg/gds) from paddy
      straw at comparatively low temperature (40  degrees C) of saccharification. P.
      lutea BG8 therefore showed great potential for cold active beta-glucosidase
      production and can be used as accessory enzyme along with commercial cellulase to
      improve saccharification efficiency.

PMID- 26202606
TI  - Morphological and confocal laser scanning microscopic investigations of the
      adductor muscle-shell interface in scallop.
AB  - The challenge of joining dissimilar advanced materials has led researchers around
      the world to search for new and more efficient solutions. This way, we can
      highlight the muscle-shell attachment in mollusk, which possessed high strength
      and toughness. In order to make clear how this "bi-material interface" derives
      its superior mechanical properties, the morphological features of the adductor
      muscle scar in Patinopecten yessoensis was investigated by means of confocal
      laser scanning microscopy (CLSM). This scar area was found to consist of a
      myostracum with many evenly distributed pit structures and a fracture section
      with a parallel arranged prism-like structure. The measured values of the
      distribution density, diameter, and depth of those pit structures were 24 +/-
      4/49,152 MUm2, 7.36 +/- 2.47 MUm, and 1 +/- 0.31 MUm respectively. Profile of
      each pit wall was arc curve without closed angle. Furthermore, CLSM micrographs
      showed that considerable micro pits (0.1-0.9 MUm in diameter) distribute round
      the pit wall and on the pit bottom. This special micromorphology is the first
      report on the adductor muscle scar in scallop. In addition, the mineral state and
      mechanical property of the scar surface was analyzed by XRD and nanoindentation
      test respectively. In general, the study results presented in this work
      elucidated that the adductor muscle of P. yessoensis was attached to the shell by
      insertion of collagen fibers and fibril bundles branched from themselves into
      pits on the myostracum. This specific connection mechanism can increase the
      strength of the interface without compromising its ductility and toughness.

PMID- 26202607
TI  - Efficacy of ruxolitinib in myeloid neoplasms with PCM1-JAK2 fusion gene.

PMID- 26202608
TI  - JAK2V617F molecular remission in a primary myelofibrosis patient treated with
      ruxolitinib.

PMID- 26202609
TI  - Transfusion dependency at diagnosis and transfusion intensity during initial
      chemotherapy are associated with poorer outcomes in adult acute myeloid leukemia.
AB  - Blood transfusions can modify host immunity and clinical outcomes in
      hematological malignancies. One thousand sixty-seven patients with acute myeloid
      leukemia (AML) were studied for their transfusion dependency at initial
      presentation and transfusion frequency during induction chemotherapy. Three
      hundred five patients (29 %) showed initial dependence to red blood cell (RBC)
      transfusion and 109 (10 %) to platelet transfusion. Transfusion dependency at
      presentation was associated with a poorer prognosis. Both initial RBC and
      platelet transfusion needs were associated with lower response rates (P = 0.04
      and P = 0.03). Median overall survival (OS) was 10.8 months for patients with RBC
      need vs 18.8 months for the other patients (P = 0.02) and 6.8 months for patients
      with platelet transfusion need vs 13.6 months for the others (P = 0.01).
      Similarly, transfusion intensity during induction therapy influenced negatively
      treatment outcome. Median transfusion burden per week was 2.5 (range 0-25.7) RBC
      units and 1.6 (range 0-15.7) platelet concentrates (PCs). Both high RBC and PC
      transfusion intensities were associated with lower response rates (P = 0.003 and
      P < 0.0001). Median OS was 9.08 months for patients with RBC transfusions >3/week
      vs 18.29 months for those with RBC transfusions <=3/week (P = 0.0003) and 10.75
      months for patients with PC transfusions >2/week vs 19.96 months for those with
      PC <=2/week (P = 0.0003). RBC and platelet transfusion intensities during
      induction therapy remained of prognostic value in multivariate analysis.
      Transfusion need at presentation and the frequency of transfusions during
      induction chemotherapy appear as strong prognostic factors. 

PMID- 26202610
TI  - Soil invertebrate community change over fuel-contaminated sites on a subantarctic
      island: An ecological field-based line of evidence for site risk assessment.
AB  - A number of fuel spills, of both recent and historic origins, have occurred on
      World Heritage-listed subantarctic Macquarie Island. Sites contaminated by mainly
      diesel fuels are undergoing remediation by the Australian Antarctic Division. The
      risks posed by these sites are being managed using a "weight of evidence"
      approach, for which this study provides a preliminary line of evidence for the
      ecological assessment component of this site management decision framework. This
      knowledge is pertinent, given the absence of environmental guidelines for fuel
      contaminants in subantarctic ecosystems. We provide a field-based, site-specific
      ecological risk assessment for soil invertebrate communities across the fuel
      spill sites, before the commencement of in situ remediation activities.
      Springtails (Collembola) were the most abundant taxa. Springtail community
      patterns showed only limited correlations with the level of fuel contamination at
      the soil surface, even when elevated levels occurred in the substratum layers. Of
      the environmental variables measured, community patterns were most strongly
      correlated with vegetation cover. We identify a suite of 6 species that
      contribute most to the community dynamics across these sites. A subset of these
      we propose as useful candidates for future development of single-species toxicity
      tests: Folsomotoma punctata, Cryptopygus caecus, Cryptopygus antarcticus and
      Parisotoma insularis. Findings from this study advance our understanding of soil
      invertebrate community dynamics within these contaminated sites, directly
      contributing to the improved management and restoration of the sites. Not only
      does this study provide an important line of evidence for the island's ecological
      risk assessment for fuel contaminants, it also enhances our understanding of the
      potential impact of fuels at other subantarctic islands.

PMID- 26202611
TI  - Scaffolding during the cell cycle by A-kinase anchoring proteins.
AB  - Cell division relies on coordinated regulation of the cell cycle. A process
      including a well-defined series of strictly regulated molecular mechanisms
      involving cyclin-dependent kinases, retinoblastoma protein, and polo-like
      kinases. Dysfunctions in cell cycle regulation are associated with disease such
      as cancer, diabetes, and neurodegeneration. Compartmentalization of cellular
      signaling is a common strategy used to ensure the accuracy and efficiency of
      cellular responses. Compartmentalization of intracellular signaling is maintained
      by scaffolding proteins, such as A-kinase anchoring proteins (AKAPs). AKAPs are
      characterized by their ability to anchor the regulatory subunits of protein
      kinase A (PKA), and thereby achieve guidance to different cellular locations via
      various targeting domains. Next to PKA, AKAPs also associate with several other
      signaling elements including receptors, ion channels, protein kinases,
      phosphatases, small GTPases, and phosphodiesterases. Taking the amount of
      possible AKAP signaling complexes and their diverse localization into account, it
      is rational to believe that such AKAP-based complexes regulate several critical
      cellular events of the cell cycle. In fact, several AKAPs are assigned as tumor
      suppressors due to their vital roles in cell cycle regulation. Here, we first
      briefly discuss the most important players of cell cycle progression. After that,
      we will review our recent knowledge of AKAPs linked to the regulation and
      progression of the cell cycle, with special focus on AKAP12, AKAP8, and Ezrin. At
      last, we will discuss this specific AKAP subset in relation to diseases with
      focus on a diverse subset of cancer. 

PMID- 26202613
TI  - Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys.
AB  - RATIONALE: Opioids remain the drugs of choice for treating moderate to severe
      pain, although adverse effects limit their use. Therapeutic utility might be
      improved by combining opioids with other drugs to enhance analgesic effects, but
      only if adverse effects are not similarly changed. OBJECTIVE: Cannabinoids have
      been shown to enhance the antinociceptive potency of opioids without increasing
      other effects; this study examined whether the effectiveness of cannabinoids is
      altered in morphine-dependent monkeys. METHODS: Four monkeys received up to 10
      mg/kg morphine twice daily. Changes in the antinociceptive effects of opioid
      receptor agonists (morphine, U50,488) and cannabinoid receptor agonists (WIN
      55,212, CP 55,940, and Delta(9)-tetrahydrocannabinol [THC]) were determined by
      measuring the latency for monkeys to remove their tails from 40, 50, 54, and 58 
      degrees C water. RESULTS: Before treatment, all drugs increased tail withdrawal
      latency from warm (54  degrees C) water. Chronic morphine treatment decreased the
      potency of each drug; the magnitude of rightward shift in dose-effect curves was
      greatest for morphine, WIN 55,212 and CP 55,940 with at least sixfold shifts for
      each drug during treatment. Discontinuation of morphine treatment resulted in
      signs that are indicative of withdrawal, including increased heart rate,
      decreased daytime activity, and tongue movement. CONCLUSION: Tolerance developed
      to the antinociceptive effects of morphine and cross-tolerance developed to
      cannabinoids under conditions that produced modest physical dependence. Compared
      with the doses examined in this study, much smaller doses of opioids have
      antinociceptive effects when given with cannabinoids; it is possible that
      tolerance will not develop to chronic treatment with opioid/cannabinoid mixtures.

PMID- 26202614
TI  - Atomoxetine accelerates attentional set shifting without affecting learning rate
      in the rat.
AB  - RATIONALE: Shifting to a new rule is a form of behavioral flexibility that is
      impaired in numerous psychiatric and neurological illnesses. Animal studies have
      revealed that this form of flexibility depends upon norepinephrine (NE)
      neurotransmission. Atomoxetine, a NE reuptake inhibitor, improves performance of
      humans in set shifting tasks. OBJECTIVE: Our objective was to validate its
      effects in a rodent set shifting task. METHODS: We tested the drug effect using
      an operant task that required a shift from a visual cue-guided behavior to a
      novel location-guided rule. RESULTS: A 1.0-mg/kg dose significantly accelerated
      rule shifting without affecting learning strategies, such as win-stay or lose
      shift. Fitting behavioral performance with a learning function provided a measure
      of learning rate. CONCLUSION: This novel analysis revealed that atomoxetine
      accelerated shifting to the new rule without affecting learning rate.

PMID- 26202612
TI  - The NEWMEDS rodent touchscreen test battery for cognition relevant to
      schizophrenia.
AB  - RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in
      Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large
      industrial-academic collaborative project aimed at developing new methods for
      drug discovery for schizophrenia. As part of this project, Work package 2 (WP02)
      has developed and validated a comprehensive battery of novel touchscreen tasks
      for rats and mice for assessing cognitive domains relevant to schizophrenia.
      OBJECTIVES: This article provides a review of the touchscreen battery of tasks
      for rats and mice for assessing cognitive domains relevant to schizophrenia and
      highlights validation data presented in several primary articles in this issue
      and elsewhere. METHODS: The battery consists of the five-choice serial reaction
      time task and a novel rodent continuous performance task for measuring attention,
      a three-stimulus visual reversal and the serial visual reversal task for
      measuring cognitive flexibility, novel non-matching to sample-based tasks for
      measuring spatial working memory and paired-associates learning for measuring
      long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen
      operant chamber and battery has high translational value across species due to
      its emphasis on construct as well as face validity. In addition, it offers
      cognitive profiling of models of diseases with cognitive symptoms (not limited to
      schizophrenia) through a battery approach, whereby multiple cognitive constructs
      can be measured using the same apparatus, enabling comparisons of performance
      across tasks. CONCLUSION: This battery of tests constitutes an extensive tool
      package for both model characterisation and pre-clinical drug discovery.

PMID- 26202615
TI  - "Dulling the Edges": Young Men's Use of Alcohol to Deal With Grief Following the
      Death of a Male Friend.
AB  - BACKGROUND: The death of a male friend can be challenging for men because
      expressions of grief can be governed and restrained by dominant ideals of
      masculinity. It is common for young men to engage in health risk practices, such
      as alcohol overuse, to deal with feelings of sadness. OBJECTIVE: This qualitative
      study investigated the ways that young men use alcohol in the process of grieving
      the accidental death of a male friend. METHOD: Participants included 35 men 19 to
      25 years old and 22 men 26 to 35 years old who participated in individual
      semistructured interviews between 2010 and 2012. RESULTS: Methodology informed by
      grounded theory and narrative analysis was used to analyse and interpret the
      transcribed interviews, focusing on the ways that men used alcohol in the grief
      process. Through data analysis we inductively derived three themes: (1) Using
      Alcohol to Dull the Pain, (2) Using Alcohol to Purge Sadness, and (3) Troubled
      Drinking. CONCLUSIONS: This study provides evidence to show that men's binge
      drinking following tragic loss is a means to express emotion and connect with
      others. Health interventions for young men who have lost a male peer need to be
      sensitive to gendered norms that inform grief practices and work with them to
      discern pathways toward recovery that promote long-term wellness.

PMID- 26202616
TI  - Point-of-care testing and INR within-subject variation in patients receiving a
      constant dose of vitamin K antagonist.
AB  - Many patients treated with vitamin K antagonists (VKA) determine their INR using
      point-of-care (POC) whole blood coagulation monitors. The primary aim of the
      present study was to assess the INR within-subject variation in self-testing
      patients receiving a constant dose of VKA. The second aim of the study was to
      derive INR imprecision goals for whole blood coagulation monitors. Analytical
      performance goals for INR measurement can be derived from the average biological
      within-subject variation. Fifty-six Thrombosis Centres in the Netherlands were
      invited to select self-testing patients who were receiving a constant dose of
      either acenocoumarol or phenprocoumon for at least six consecutive INR
      measurements. In each patient, the coefficient of variation (CV) of INRs was
      calculated. One Thrombosis Centre selected regular patients being monitored with
      a POC device by professional staff. Sixteen Dutch Thrombosis Centres provided
      results for 322 selected patients, all using the CoaguChek XS. The median within
      subject CV in patients receiving acenocoumarol (10.2 %) was significantly higher
      than the median CV in patients receiving phenprocoumon (8.6 %) (p = 0.001). The
      median CV in low-target intensity acenocoumarol self-testing patients (10.4 %)
      was similar to the median CV in regular patients monitored by professional staff
      (10.2 %). Desirable INR analytical imprecision goals for POC monitoring with
      CoaguChek XS in patients receiving either low-target intensity acenocoumarol or
      phenprocoumon were 5.1 % and 4.3 %, respectively. The approximate average value
      for the imprecision of the CoaguChek XS, i. e. 4 %, is in agreement with these
      goals. 

PMID- 26202617
TI  - [Personal motif in art].
AB  - One of the basic questions of the art psychology is whether a personal motif is
      to be found behind works of art and if so, how openly or indirectly it appears in
      the work itself. Analysis of examples and documents from the fine arts and
      literature allow us to conclude that the personal motif that can be identified by
      the viewer through symbols, at times easily at others with more difficulty, gives
      an emotional plus to the artistic product. The personal motif may be found in
      traumatic experiences, in communication to the model or with other emotionally
      important persons (mourning, disappointment, revenge, hatred, rivalry, revolt
      etc.), in self-searching, or self-analysis. The emotions are expressed in
      artistic activity either directly or indirectly. The intention nourished by the
      artist's identity (Kunstwollen) may stand in the way of spontaneous self
      expression, channelling it into hidden paths. Under the influence of certain
      circumstances, the artist may arouse in the viewer, consciously or unconsciously,
      an illusionary, misleading image of himself. An examination of the personal motif
      is one of the important research areas of art therapy. 

PMID- 26202618
TI  - [Emancipation of the works of artists with psychiatric illness - Artistic
      reflections from the twentieth century and the Art Brut].
AB  - The study presents the emancipation of the artworks of psychiatric patients
      through the review of four centuries, focusing on some of the most important
      medical cultural and art historical stages of the period between the 18th and the
      21st century, which is a particularly relevant era in this regard. It touches on
      the collections linked to psychiatrists and hospitals that were formed primarily
      on the basis of the researches that were analyzing the connection between
      creativity and mental illness. After that, the study discusses the ever-changing
      attitudes and preferences of artists' and major artistic movements towards
      psychosis and the pictorial world of the psychotic. With great care, it analyses
      the aesthetic category of the art brut, which is connected to the French painter
      Jean Dubuffet and was born in the middle of the 1940s, and the relationship
      between contemporary art and art brut. In connection with some of the most
      significant art brut collections and exhibitions, the works of a few classical
      and contemporary art brut artists are also discussed (Adolf Wolfli, Louis
      Soutter, Aloise Corbaz, August Walla ). 

PMID- 26202619
TI  - [Chance meeting of psychiatry and art on the "dissecting table"].
AB  - This paper shows one of many aspects of the history of the Hungarian psychiatry
      between the two world wars. The data were collected from the "Hungarian Museum of
      Mind" opened for the public in 1931. It focuses on the collecting policy and the
      research topics of Hungarian psychiatrists working in the asylums in those days.
      In 2007 Lipotmezo (the Hungarian Psychiatric and Neurological Institution the
      biggest Hungarian asylum since its foundations in 1868) was closed. Its art
      collection was rescued by the Hungarian Academy of Science. From 2007 this
      collection has been named The Psychiatric Art Collection of the HAS, maintained
      by The Research Centre for the Humanities of the Hungarian Academy of Science.
      The artistic objects and documents are properly stored and available for
      research. Two art historians are in charge of curating the exhibitions and
      leading the research on the psychiatric art in the context of history,
      psychiatric history and contemporary culture. This work follows the well
      established practice of the eighties and nineties when the art historian Edit
      Plesznivy expert in this subject listed the pieces of this historical collection,
      and through the context of outsider art and art therapy she channeled it into the
      field of art institutions. Leaving the hospital environment and having been
      introduced to the academic world the research is looking toward the collection
      has been changed and new perspectives have been opened. Beside the art works of
      the patients living as inmates in mental hospitals, the collecting work and
      therapeutic practices of the mental physicians became a significant research
      topic also. Arpad Selig as an assistant physician at the Mental and Neurological
      Clinic in Lipotmezo started to collect the patients' works of art in the first
      decade of twentieth century. During the 1920s he was appointed the director of
      Angyalfold Asylum found in 1883. Selig died in 1929 and the Museum of Mind named
      after its enthusiastic founder Selig was registered in the official list of
      museums in 1932. In the 1930s Istvan Zsako the physician director of Angyalfold
      Asylum took care of the collection. He enriched it with further historical
      documents on the institution, bibliographies, press cuts, tableaux and
      photographic albums referring to the institution and the research practiceses of
      the physicians. After Zsako was appointed the director of Lipotmezo the
      collections of Lipotmezo and Angyalfold were joined. The collection suffered
      during the World War II and this period is can be viewed as a caesura in the
      practice of collecting. Later, from the late fifties, the physician Fekete Janos,
      head of the nurse training in Lipotmezo was in charge of the collection. He
      focused on sorting and installation of the remnants and also collected new works
      of the inpatients. During the seventies the psychotherapy was inaugurated and in
      the eighties the art therapy exercises began. However, through the reconstruction
      of the therapeutical and collecting practices show that these evolving art
      therapy practices partly rooted in the work of psychiatric treatment in the
      twenties and thirties. Psychiatrists, who lived in the asylums too, supported the
      so called "noble entertainments" - including artistic drawing, painting, reading
      and playing musical instruments - and as a part of the daily routines of these
      mental institutions they formed a locally particular modus operandi of therapy.
      The inmates of the asylums, the physicians and patients cooperated to enrich the
      collection which was a venue to represent the life of the institution and to
      demonstrate the research of the physicians. Despite of the significant
      differences between the pre- and postwar periods concerning the sociocultural and
      political structures there is a well defined connection between "curing and
      curating". 

PMID- 26202620
TI  - [Role of the body image in creativity--a group of objects as an attempt for
      contextualization].
AB  - The Psychiatric Institutes have supported the different forms of self-expression
      from the very beginning, sometimes realizing therapeutic goals as well. Under
      this point theatrical phenomenon was held too. Physicians often created such
      scenic actions themselves. The visual, pictorial expressions have begun to be
      shown parallel to the representation of such scenic world. That was the context
      to create a number of psychiatric art collections. By this kind of theatre based
      on esthetical judgment visual creations have been shown to the greater public
      promoting the representation of integral, intact and differing body image. The
      exotic, the bizarre, differing from the expected, the different was in the focus.
      It is always a question who is inside and who is outside, who can see and who can
      know the secret and who cannot. Starting from space - and from a psychic point of
      view - the perspective and the focus are also important attitudes. It is
      important from where we look at things, are we included in the studied area or
      are we watching it from outside? Are we the ones to study something or are we
      being watched? Only the stability of our identity enables us to play different
      roles. I find it important how the ability to accept one's own body limits, the
      formation of body image influences one's visual expression in the mirror of the
      surrounding society and how it appears in the creative process. Being traumatized
      may lead to dissociation, post-traumatic disorder or some other psychosomatic
      complaints. People who endure some trauma diverge from the real situation that
      makes them suffer if they feel that their state is hopeless, if they cannot see
      any way out. One possible way to come to grips with some trauma is to create, to
      frame, which can be either negative or positive. In the negative sense it leads
      to remembrance, trace-leaving, the process of grief, frustration, mutilation and
      sacrifice. On the other hand, in the positive sense one is able to build up
      something through all these. We can also look at this process from the male or
      female viewpoint. Through such approach and with such questions in mind, I
      analyze a group of graphic objects of the Psychiatric Art Collection of the
      Hungarian Academy of Sciences.

PMID- 26202621
TI  - [Music in the picture -- musical scores and other music-related pictorial
      elements in the visual artworks of schizophrenic patients].
AB  - Since the beginning of the 20th century music scores and other music releated
      pictoral elements have repeteadly appeared in psychotic patients' visual
      artworks. Interestingly, little attention was paid to these enigmatic forms of
      psychopathological art expression till the 1970s. This essay investigates the
      underlying psychopathology and the psychodynamic basis of musical elements
      applied in psychotic patients' visual art expression within a phenomenological-
      intersubjective framework integrating the art-historical context of the 20th
      century. As an illustration, artworks of the psychopathological art collection of
      the Department of Psychiatry and Psychotherapy, Medical Faculty, University of
      Pecs, Hungary are presented. 

PMID- 26202622
TI  - [Effect of the media on the drawings of 14-16 years old adolescents].
AB  - Due to the pervasive presence of the Internet, the popularity of social
      networking sites and the general use of electronic tools in our age, the
      different idols and celebrities of media, film heroes or fictional characters
      have become an everyday part of a teenager's communication and cogitation. These
      themes often appear on adolescent drawings and they are often full of individual
      content and thus become the forms of self-expression. In my study I draw the
      attention to this phenomenon by presenting some examples. One characteristic area
      of it is when teenagers fill the schematic signs, icons and emoticons of the
      media with individual denotations, which can express anxiety or aggressive
      feelings hidden into these symbols. Identifying with movie characters or scenes
      often has a function to accomplish wishes. Similarly to role models, the
      identification with an idealised character may mean that the adolescent lives
      through the characteristic he longs for. The fictional characters of a film can
      be the tool of self-irony or self-taunting too, which can also refer to anxiety
      or aggressive feelings. In other cases pupils reveal very complex contents about
      selfknowledge through the scenes or characters of a film, which are difficult to
      get into shape in a verbal way. Finally, the frequent appearance of some famous
      trademarks in drawings could be an indication of matter of prestige and these
      emblems could be interpreted as a way of self-expression in peer groups. 

PMID- 26202623
TI  - [Trait-aggression and suicide of Vincent van Gogh].
AB  - Although in recent decades the literature has paid special attention to Vincent
      van Gogh's life, work and illness, there has still not been an examination of the
      connections between his trait aggression and his suicide. The present study
      traces, in the light of this trait aggression, the predictive factors that can be
      observed on the path leading to the artist's suicide. Biographical documents,
      case history data, as well as letters and the findings of earlier research have
      been used in the course of the analysis. Among the distal suicide risk factors we
      find a positive family anamnesis, childhood traumas (emotional deprivation,
      identity problems associated with the name Vincent), a vagrant, homeless way of
      life, failures in relationships with women, and psychotic episodes appearing in
      rushes. The proximal factors include the tragic friendship with Gauguin
      (frustrated love), his brother Theo's marriage (experienced as a loss), and a
      tendency to self-destruction. Both factor groups on the one hand determined the
      course of development of the trait aggression and on the other can also be
      regarded as a manifestation of that trait aggression. It can be said that the
      trait aggression played an important role in Van Gogh's suicide. 

PMID- 26202624
TI  - [Trait-aggression and conscious poetic attitude in the background of Attila
      Jozsef's suicide].
AB  - Although recently many studies have indicated close connection between aggressive
      behaviour and suicide, and we can infer at Attila Jozsef's high trait-aggression
      from several cases, there is no research so far that would analyse the topic of
      the poet's aggression. We examine in this study the high trait-aggression and
      conscious poetic attitude of Attila Jozsef and put the question how could those
      two contribute to his suicide. Recollections of Attila Jozsef's contemporaries
      reveal that the poet's life was accompanied along with auto- and
      heteroaggression. By analysing his Rorschach-test, we can also conclude on the
      weakness of his aggression-control. During his psychoanalytic treatment from 1931
      on, some difficult memories and unacceptable desires became revoked, and his
      aggressive outbreaks became unmanageable, first of all against some females in
      his life. His free-association works from this period are full of rude,
      incestuous, aggressive expressions. In spite of these, there is no trace of
      aggression in his poems - he masks his aggression in them by keeping precisely to
      formal criteria. We suppose that behind the masking there are unconscious
      processes, such as a very strong desire to get attached and fear of solitude that
      led to his aspiration to consciously form "the myth of the good poet". Art's
      healing power could not prevail as the spontaneous creative process has been
      turned into a conscious one. His impulses that came to light in the analytic
      process and were only partly sublime may have returned thus and became urgent and
      pressing again. We suppose that his high trait-aggression and his conscious
      poetic attitude together contributed to his life's tragic ending. 

PMID- 26202625
TI  - [Codependence in Peter Hajnoczy's novella Death rode out of Persia].
AB  - It is assumed that in connection with literature the artistic product generates
      interaction between the creator and the recipient, as in the all other cases of
      art. The formation of a writing leads to the birth of the reading, while the
      reader creates a new quality weaving artistic literature into a subjective
      context, this is how the so-called "personal reading" springs into existence. The
      Death rode out of Persia (A halal kilovagolt Perzsiabol) written by Peter
      Hajnoczy - which is about the everyday life of a man suffering from alcoholism 
      facilitates not only the formation of a subjective reading based on emotional
      impressions, but also provokes the formation of an analytic reading which
      reflects on the phenomena of addiction and the loss of control. This kind of
      focused analysis claims to let the particular art product and the professional
      literature of addictology meet on the field of alcoholism and codependence. 

PMID- 26202626
TI  - [The role of art therapy in the rehabilitation of psycho-socially disabled
      people].
AB  - The present review focuses on the generally accepted and applied community
      psychiatry based models of psycho-social rehabilitation. The basics of the
      Strenghts model and the Recovery based model are introduced in this paper. Both
      models can be assisted by art therapy in various ways. The forms and the
      therapeutic factors of art therapy are also discussed, as well as the effects of
      the creating experience during the art therapy sessions. The authors introduce
      the good practice of the Moravcsik Foundation with highlights in two special
      areas that are beyond the generally applied art therapy work and representing
      important support in reaching the goals set during the rehabilitation process.
      Further, the authors describe the Budapest Art Brut Gallery and the PsychArt24
      art marathon project in details. 

PMID- 26202628
TI  - Effect of nucleic acid binding dyes on DNA extraction, amplification, and STR
      typing.
AB  - We report on the effects of six dyes used in the detection of DNA on the process
      of DNA extraction, amplification, and detection of STR loci. While dyes can be
      used to detect the presence of DNA, their use is restricted if they adversely
      affect subsequent DNA typing processes. DiamondTM Nucleic Acid Dye, GelGreenTM,
      GelRedTM, RedSafeTM, SYBR((r)) Green I, and EvaGreenTM were evaluated in this
      study. The percentage of dye removed during the extraction process was determined
      to be: 70.3% for SYBR((r)) Green I; 99.6% for RedSafeTM; 99.4% for EvaGreenTM;
      52.7% for DiamondTM Dye; 50.6% for GelRedTM, and; could not be determined for
      GelGreenTM. It was then assumed that the amount of dye in the fluorescent
      quantification assay had no effect on the DNA signal. The presence of all six
      dyes was then reviewed for their effect on DNA extraction. The t-test showed no
      significant difference between the dyes and the control. These extracts were then
      STR profiled and all dyes and control produced full DNA profiles. STR loci in the
      presence of GelGreen(TM) at 1X concentration showed increased amplification
      products in comparison to the control samples. Full STR profiles were detected in
      the presence of EvaGreenTM (1X), although with reduced amplification products.
      RedSafeTM (1X), DiamondTM Dye (1X), and SYBR((r)) Green I (1X) all exhibited
      varying degrees of locus drop-out with GelRedTM generating no loci at all. We
      provide recommendations for the best dye to visualize the presence of DNA profile
      as a biological stain and its subsequent amplification and detection.

PMID- 26202627
TI  - Atrial fibrillation screening in pharmacies using an iPhone ECG: a qualitative
      review of implementation.
AB  - BACKGROUND: Atrial fibrillation guidelines advocate screening to identify
      undiagnosed atrial fibrillation. Community pharmacies may provide an
      opportunistic venue for such screening. OBJECTIVE: To explore the experience of
      implementing an atrial fibrillation screening service from the pharmacist's
      perspective including: the process of study implementation; the perceived
      benefits; the barriers and enablers; and the challenges for future sustainability
      of atrial fibrillation screening within pharmacies. Setting Interviews were
      conducted face-to-face in the pharmacy or via telephone, according to pharmacist
      preference. METHOD: The 'SEARCH-AF study' screened 1000 pharmacy customers aged
      >=65 years using an iPhone electrocardiogram, identifying 1.5 % with undiagnosed
      atrial fibrillation. Nine pharmacists took part in semi-structured interviews.
      Interviews were transcribed in full and thematically analysed. MAIN OUTCOME
      MEASURE: Qualitative analysis of the experience of implementing an AF screening
      service from the pharmacist's perspective. RESULTS: Four broad themes relating to
      service provision were identified: (1) interest and engagement in atrial
      fibrillation screening by pharmacists, customers, and doctors with the novel,
      easy-to-use electrocardiogram technology serving as an incentive to undergo
      screening and an education tool for pharmacists to use with customers; (2)
      perceived benefits to the pharmacist including increased job satisfaction,
      improvement in customer relations and pharmacy profile by fostering enhanced
      customer care and the educational role of pharmacists; (3) implementation
      barriers including managing workflow, and enablers such as personal approaches
      for recruitment, and allocating time to discuss screening process and fears; and,
      (4) potential for sustainable future implementation including remuneration linked
      to government or pharmacy incentives, combined cardiovascular screening, and
      automating sections of risk-assessments using touch-screen technology.
      CONCLUSION: Atrial fibrillation screening in pharmacies is well accepted by
      pharmacists and customers. Many pharmacists combined atrial fibrillation
      screening with other health screens reporting improved time-efficiency and
      greater customer satisfaction. Widespread implementation of atrial fibrillation
      screening requires longterm funding, which could be provided for a combined
      cardiovascular screening service. Further research could focus on feasibility and
      cost-effectiveness of combined cardiovascular screening in pharmacies.

PMID- 26202631
TI  - Finding Missing Proteins from the Epigenetically Manipulated Human Cell with
      Stringent Quality Criteria.
AB  - The chromosome-centric human proteome project (C-HPP) has made great progress of
      finding protein evidence (PE) for missing proteins (PE2-4 proteins defined by the
      neXtProt), which now becomes an increasingly challenging field. As a majority of
      samples tested in this field were from adult tissues/cells, the developmental
      stage specific or relevant proteins could be missed due to biological source
      availability. We posit that epigenetic interventions may help to partially bypass
      such a limitation by stimulating the expression of the "silenced" genes in adult
      cells, leading to the increased chance of finding missing proteins. In this
      study, we established in vitro human cell models to modify the histone
      acetylation, demethylation, and methylation with near physiological conditions.
      With mRNA-seq analysis, we found that histone modifications resulted in overall
      increases of expressed genes in an even distribution manner across different
      chromosomes. We identified 64 PE2-4 and six PE5 proteins by MaxQuant (FDR < 1% at
      both protein and peptide levels) and 44 PE2-4 and 7 PE5 proteins by Mascot (FDR <
      1% at peptide level) searches, respectively. However, only 24 PE2-4 and five PE5
      proteins in Mascot, and 12 PE2-4 and one PE5 proteins in MaxQuant searches could,
      respectively, pass our stringently manual spectrum inspections. Collectively, 27
      PE2-4 and five PE5 proteins were identified from the epigenetically modified
      cells; among them, 19 PE2-4 and three PE5 proteins passed FDR < 1% at both
      peptide and protein levels. Gene ontology analyses revealed that the PE2-4
      proteins were significantly involved in development and spermatogenesis, although
      their chemical-physical features had no statistical difference from the
      background. In addition, we presented an example of suspicious PE5 peptide
      spectrum matched with unusual AA substitutions related to post-translational
      modification. In conclusion, the epigenetically manipulated cell models should be
      a useful tool for finding missing proteins in C-HPP. The mass spectrometry data
      have been deposited to the iProx database (accession number: IPX00020200). 

PMID- 26202632
TI  - Interferon for Chinese patients with chronic hepatitis B e antigen-positive
      diseases-the controversy arises again?

PMID- 26202629
TI  - KAT2B polymorphism identified for drug abuse in African Americans with regulatory
      links to drug abuse pathways in human prefrontal cortex.
AB  - Drug abuse is a common and heritable set of disorders, but the underlying genetic
      factors are largely unknown. We conducted genome-wide association studies of drug
      abuse using 7 million imputed single nucleotide polymorphisms (SNPs) and
      insertions/deletions in African Americans (AAs; n = 3742) and European Americans
      (EAs; n = 6845). Cases were drawn from the Urban Health Study of street-recruited
      people, who injected drugs and reported abusing opioids, cocaine, marijuana,
      stimulants and/or other drugs 10 or more times in the past 30 days, and were
      compared with population controls. Independent replication testing was conducted
      in 755 AAs and 1131 EAs from the Genetic Association Information Network. An
      intronic SNP (rs9829896) in the K(lysine) acetyltransferase 2B (KAT2B) gene was
      significantly associated with drug abuse in AAs (P = 4.63 * 10-8 ) and
      independently replicated in AAs (P = 0.0019). The rs9829896-C allele (frequency =
      12%) had odds ratios of 0.68 and 0.53 across the AA cohorts: meta-analysis P =
      3.93 * 10-10 . Rs9829896-C was not associated with drug abuse across the EA
      cohorts: frequency = 36% and meta-analysis P = 0.12. Using dorsolateral
      prefrontal cortex data from the BrainCloud cohort, we found that rs9829896-C was
      associated with reduced KAT2B expression in AAs (n = 113, P = 0.050) but not EAs
      (n = 110, P = 0.39). KAT2B encodes a transcriptional regulator in the cyclic
      adenosine monophosphate and dopamine signaling pathways, and rs9829896-C was
      associated with expression of genes in these pathways: reduced CREBBP expression
      (P = 0.011) and increased OPRM1 expression (P = 0.016), both in AAs only. Our
      study identified the KAT2B SNP rs9829896 as having novel and biologically
      plausible associations with drug abuse and gene expression in AAs but not EAs,
      suggesting ancestry-specific effects.

PMID- 26202633
TI  - Yttrium-90 radioembolization for hepatocellular carcinoma in hepatitis B:
      commentary on a 103-patient Asian cohort.

PMID- 26202634
TI  - Hedgehog signaling and radiation induced liver injury: a delicate balance.
AB  - Radiation-induced liver disease (RILD) is a major limitation of radiation therapy
      (RT) for the treatment of liver cancer. Emerging data indicate that hedgehog (Hh)
      signaling plays a central role in liver fibrosis and regeneration after liver
      injury. Here, we review the potential role of Hh signaling in RILD and propose
      the temporary use of Hh inhibition during liver RT to radiosensitize HCC tumor
      cells and inhibit their progression, while blocking the initiation of the
      radiation-induced fibrotic response in the surrounding normal liver. 

PMID- 26202635
TI  - Role of circulating tumor cells and cancer stem cells in hepatocellular
      carcinoma.
AB  - Circulating tumor cells (CTC) and cancer stem cells (CSC) have been proposed as
      tools for detection and characterization of disease and individualization of
      therapy in patients with many solid tumors. Several automated and semi-automated
      techniques for identification and isolation of these cells from blood have been
      proposed and reviewed mostly focusing on their feasibility. In this mini review
      we summarize the recent relevant literature on this topic and discuss the
      clinical usability of measuring CTC and CSC in peripheral blood in patients with
      hepatocellular carcinoma (HCC). Besides literature, the basis for this evaluation
      was the authors' experience with treating HCC and research experience on CSC and
      CTC. Few original reports and reviews have been published focusing on CTC and CSC
      in HCC. Though HCC is one of the five most common malignancies worldwide only
      recently these cells have come into focus for detection and characterization of
      this disease that is characterized by high plasticity and malignancy. A focused
      and prospective validation of the clinical usability of detecting these cells in
      HCC is still needed, but results seem promising that they may add great benefit
      for early detection and individualization of therapy. 

PMID- 26202636
TI  - Oncogenic signaling pathways and origins of tumor-initiating stem-like cells of
      hepatocellular carcinomas induced by hepatitis C virus, alcohol and/or obesity.
AB  - This review article discusses the importance and oncogenic signaling pathways of
      tumor-initiating cells (TICs) in several etiologies of hepatocellular carcinomas
      (HCCs) induced by hepatitis C virus (HCV), alcohol, obesity and/or chemicals.
      Stem cells may be present in cancer tissue, and a hierarchy of cells is formed,
      as is the case for normal tissue. Tumor formation, growth and propagation are
      maintained by a small proportion of cells with stem cell-like properties. TICs
      are present in alcohol-fed HCV transgenic mice, diethylnitrosamine/phenobarbital
      treated mice (chemical carcinogenesis) and Spnb2 +/- mice (defective TGF-beta
      signal). Alcohol/obesity-associated endotoxemia induces the stem cell marker
      Nanog through TLR4 signaling to generate TICs and liver tumors in several HCC
      models. The oncogenic pathway (such as the STAT3 and TLR4-NANOG pathway) and
      mechanism of generation of TICs of HCCs associated with HCV, alcohol and obesity
      are discussed. Understanding the molecular stemness signaling and cellular
      hierarchy and defining key TIC-specific genes will accelerate the development of
      novel biomarkers and treatment strategies. This review highlights recent advances
      in understanding the pathogenesis of liver TICs and discusses unanswered
      questions about the concept of liver TICs. (This project was supported by NIH
      grants 1R01AA018857 and P50AA11999). 

PMID- 26202637
TI  - The role of collateral veins detected by endosonography in predicting the
      recurrence of esophageal varices after endoscopic treatment: a systematic review.
AB  - Endoscopic therapy is the principal method of treatment for esophageal varices.
      The recurrence of varices is still common following endoscopic treatment. The aim
      was to identify predictive factors for variceal recurrence detected by
      endosonography. We performed a systematic review of studies published prior to
      June 2013. Studies analyzing gastroesophageal collateral veins as risk factors
      for variceal recurrence after endoscopic treatment were included. The primary
      outcome was to identify predictive factors for variceal recurrence investigated
      by endosonography. After a full-text review, 13 studies were included in our
      analysis. Analysis of risk factors was not possible for all studies included.
      Perforating veins and periesophageal collateral veins were related to a higher
      risk of variceal recurrence (OR = 3.93; 95 % CI 1.06-14.51; I (2) = 96 %; OR =
      2.29; 95 % CI 1.58-3.33; I (2) = 55 %). Analysis of cardiac intramural veins and
      paragastric/cardiac collateral veins showed the same trend, but without reaching
      statistical significance because of the small group size and wide CI (OR = 3.72;
      95 % CI 0.14-101.53; I (2) = 91 %; OR = 1.85; 95 % CI 0.84-4.07; I (2) = 0 %).
      Analysis of other collateral veins as risk factors for variceal recurrence and
      analysis of risk factors with regard to the endoscopic treatment method was not
      possible because of the limited number of cases and different methodologies. A
      positive association between variceal recurrence and type and grade of collateral
      veins, investigated by endosonography, was demonstrated. Endosonography is a
      promising tool for predicting recurrence of esophageal varices following
      endoscopic treatment. These findings should be interpreted with caution because
      of the heterogeneity of the studies. 

PMID- 26202638
TI  - Comparison of first- and second-wave DAAs for HCV GT1: efficacy, safety,
      tolerability, and regimen complexity.

PMID- 26202639
TI  - Patients with interferon-induced HBeAg seroconversion have a higher risk of HBV
      reactivation and HBeAg seroreversion.
AB  - PURPOSE: It remains unclear whether chronic hepatitis B patients who undergo
      interferon (IFN)-induced hepatitis B e antigen (HBeAg) seroconversion have a
      higher risk of hepatitis B virus (HBV) reactivation and HBeAg seroreversion than
      those with spontaneous HBeAg seroconversion. METHODS: A total of 80 and 251 non
      cirrhotic patients with interferon-induced and spontaneous HBeAg seroconversion,
      respectively, were analyzed. RESULTS: Compared to spontaneous HBeAg
      seroconverters, more IFN-induced HBeAg seroconverters were males (p = 0.004). For
      all patients, the IFN-induced HBeAg seroconverters faced a higher risk of HBV
      reactivation and HBeAg seroreversion than spontaneous HBeAg seroconverters (p <
      0.001). For spontaneous HBeAg seroconverters, age at HBeAg seroconversion, male
      sex, HBV genotype C, and pre-S deletions were independent predictors of HBV
      reactivation. For IFN-induced HBeAg seroconverters, older age at baseline and HBV
      genotype C were independent predictors of HBV reactivation. To determine whether
      the difference in the rates of HBV reactivation or HBeAg seroreversion between
      two groups was age-dependent, patients were grouped and analyzed according to
      their age at HBeAg seroconversion (20-30, 31-39, >=40 years). IFNs treatment was
      an independent factor in HBV reactivation and HBeAg seroreversion only in the
      groups of patients 31-39 and >=40 years of age, but not in the group of patients
      20-30 years of age. CONCLUSIONS: IFN-induced rather than spontaneous HBeAg
      seroconversion was associated with higher risk of HBV reactivation and HBeAg
      seroreversion, especially in patients who were older than 30 years at HBeAg
      seroconversion.

PMID- 26202640
TI  - Consensus cost-effectiveness model for treatment of chronic hepatitis B in Asia
      Pacific countries.
AB  - PURPOSE: The Asian Pacific Association for the Study of the Liver (APASL)
      convened an international working party to develop a consensus cost-effectiveness
      model for treatment of Hepatitis B in Asia Pacific countries in March 2010.
      METHODS: The working party consisted of expert hepatologists, virologists and
      epidemiologists from 11 representative countries in the Asia Pacific region.
      Meetings were conducted at the 20th APASL Annual Meeting in 2010 to determine
      consensus estimates for modeling and at the 21st and 22nd APASL meetings in 2011
      and 2012, respectively to review and approve the models. RESULTS: The consensus
      cost-effectiveness model used Singapore as base case analysis and was validated
      using actual data from the Singapore Cancer, Diseases and Death Registries.
      Simulation for Singapore, China, Thailand, Pakistan, Taiwan and Korea were
      performed. Antivirals with high resistance barriers like entecavir and tenofovir
      had the highest retail cost but were the most cost-effective therapy in developed
      countries such as Singapore, Taiwan and Korea while generic tenofovir was most
      cost effective in Thailand and Pakistan. The cost effectiveness of different
      treatment strategies varied significantly between countries and was affected by
      medication cost, economic affordability, access to liver transplantation and the
      prevailing health of the general population. CONCLUSION: Choosing treatment
      strategies for hepatitis B based on low retail drug cost can be misleading
      because more expensive drugs may be more cost effective when considering long
      term health outcomes and costs. Cost-effectiveness data should be individualized
      to countries based on their unique socio-economic conditions. Governmental
      policies which subsidize more costly drugs that have lower risk of drug
      resistance can benefit more patients.

PMID- 26202641
TI  - Survival and pattern of tumor progression with yttrium-90 microsphere
      radioembolization in predominantly hepatitis B Asian patients with hepatocellular
      carcinoma.
AB  - PURPOSE: Intra-arterial yttrium-90 ((90)Y) microsphere radioembolization (RE) is
      an emerging treatment option with good outcomes reported predominantly in
      hepatitis C Western populations with hepatocellular carcinoma (HCC). We report
      outcomes in predominantly hepatitis B Asian patients treated with (90)Y-RE
      focusing on overall survival (OS), time to progression (TTP), tumor response,
      pattern of tumor recurrence and adverse events. Prognostic factors for survival
      were also identified. METHODS: A retrospective cohort study was conducted in a
      single tertiary institution. All non-trial patients treated with (90)Y-RE at our
      institution from 1 January 2008 to 30 June 2012 were included. RESULTS: Data from
      103 consecutive patients were analyzed. The majority of patients were Child-Pugh
      class A (59.2 %) and Barcelona Clinic Liver Cancer (BCLC) stage C (68.9 %).
      Median OS was 14.4 months (95 % CI 11.0-22.2), which varied by disease stage:
      Child-Pugh A, 21.7 months; Child-Pugh B, 7.1 months; BCLC B, 23.8 months; BCLC C,
      11.8 months. Response and disease control rates by RECIST 1.1 were 21.2 and 59.6
      %, respectively, while disease control for index lesions treated with (90)Y-RE
      was 100 %. Development of new intrahepatic lesions was the main reason for
      eventual disease progression. Median overall TTP was 5.3 months (95 % CI 4.1
      10.0). Pretreatment vascular invasion, low serum albumin and elevated total
      bilirubin levels predicted poorer survival. CONCLUSIONS: Survival outcomes in
      hepatitis B Asian patients treated with (90)Y-RE for HCC are comparable to
      hepatitis C Western populations. While disease control for lesions treated with
      (90)Y-RE is excellent, the development of new lesions suggests a role for
      concomitant systemic therapy.

PMID- 26202642
TI  - Upregulation of CD147 protects hepatocellular carcinoma cell from apoptosis
      through glycolytic switch via HIF-1 and MCT-4 under hypoxia.
AB  - PURPOSE: Hypoxia is a vital factor in supporting and directing hepatocellular
      carcinoma (HCC) progression. HIF-1 transactivates target genes involved in
      metabolic reprogramming and antiapoptosis under hypoxia. However, key molecules
      involved in HCC hypoxia adaptation remain to be characterized. The aim of this
      study was to investigate the mechanism and biological function of CD147 on HCC
      cells resistant to apoptosis under hypoxic conditions. METHODS: Apoptotic rates
      of hypoxia-treated HCC cells were investigated by flow cytometer, and the
      expression levels of CD147, HIF-1alpha, MCT-1 and MCT-4 were assayed by immune
      blot. The in vitro glycolytic capacity was investigated in SMMC-7721 cells and
      7721-shCD147 cells (CD147 is stably knocked down). Immunohistochemical staining
      of CD147, Glut-1, MCT-1, MCT-4, LAT-1 and CD98 was detected in tumor tissues from
      a xenograft model. Immunofluorescence double-labeled staining allowed further
      exploration of the expression levels and localizations of CD147, MCT-1 and MCT-4.
      RESULTS: Upregulation of CD147 under hypoxia correlates with higher viability of
      HCC cells compared with that in HSC cells. Silencing of CD147 significantly
      inhibited the glycolytic rate and induced apoptosis in SMMC-7721 cells. The
      expression level of lactate secretion transporter MCT-1/MCT-4 is dependent on
      CD147, while the expression level of Glut-1, LAT-1 and CD98 remained unchanged.
      Particularly, MCT-4 is demonstrated to be essential for the membranal
      localization of CD147. CONCLUSIONS: With the above findings, we conclude that
      within the HCC hypoxic microenvironment, upregulation of CD147 and MCT-4 involved
      in glycolytic reprogramming is decisively important for the viability of HCC
      cells under hypoxia adaptation.

PMID- 26202643
TI  - Neonatal streptozotocin treatment causes type 1 diabetes and subsequent
      hepatocellular carcinoma in DIAR mice fed a normal diet.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) represents a major health challenge
      because of its increasing morbidity and mortality. The establishment of useful
      models of HCC can significantly contribute to unveiling its pathophysiology. We
      developed a novel mouse model of HCC based on type 1 diabetes and reported its
      histopathological features. METHODS: Newborn male ddY, Institute for Animal
      Reproduction (DIAR) mice were divided into two groups on the basis of
      streptozotocin treatment, which induces type 1 diabetes. Streptozotocin was
      subcutaneously injected (60 mg/g) into the treated group (DIAR-nSTZ mice),
      whereas physiologic solution was injected into the control group (DIAR-control
      mice) at 1.5 days after birth. All mice were fed a normal diet and
      histopathologically assessed at 6, 8, 10, 12, 19, and 27 weeks of age. RESULTS:
      At 8 weeks, small hepatocytic nodules with mild to moderate cellular atypia were
      observed in the livers of DIAR-nSTZ mice, which progressed to large hepatocytic
      nodules with cellular atypia and infiltrating growth at 12 weeks, identical to
      those in well-differentiated human HCC. At 19 and 27 weeks, moderately
      differentiated HCC was observed in all DIAR-nSTZ mice. Conversely, no neoplastic
      findings were evident in DIAR-control mice. No steatosis or fibrosis was evident
      in either group. Immunohistochemical analysis revealed that all nodules observed
      in DIAR-nSTZ mice were positive for glutamine synthetase. CONCLUSIONS: In DIAR
      nSTZ mice, the development of HCC with similarity to human HCC and high
      reproducibility can be achieved using a short and simple protocol. We believe
      that this model will be useful for studying liver carcinogenesis.

PMID- 26202644
TI  - Pre-endurance training prevents acute alcoholic liver injury in rats through the
      regulation of damaged mitochondria accumulation and mitophagy balance.
AB  - AIM: The aim of this study is to investigate the effect of pre-endurance training
      on the prevention of alcohol-induced acute hepatic injury and on hepatic
      mitophagy. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided
      into four groups: (1) control group, (2) 12-week exercise training group, (3) 5
      day alcohol intake group, and (4) 12-week exercise training plus 5-day alcohol
      intake group. The rats were examined to determine the following: BCL2/adenovirus
      E1B 19 kDa protein-interacting protein 3 (BNIP3), hypoxia-inducible factor-1alpha
      (HIF-1alpha), cytochrome P450 2E1 (CYP2E1), alcohol dehydrogenase (ADH),
      microtubule-associated protein 1 light chain 3 (LC3II), Beclin1 mRNA and protein
      expressions, mitochondrial reactive oxygen species (ROS) production,
      mitochondrial thiobarbituric acid-reactive substances (TBARS) level, aconitase
      and ATP synthase activities, mitochondrial inner membrane potential, NADH/NAD(+)
      ratio, triglyceride (TG), the number of mtDNA and mitochondrial respiration
      functions in liver tissue, and serum ALT and AST. RESULTS: Pre-endurance training
      attenuated acute alcohol treatment-induced increase in mitochondrial TBARS, ROS
      production, NADH/NAD(+) ratio, state 4 respiration rate, TG, serum ALT and AST,
      as well as BNIP3, HIF-1alpha, LC3II, and Beclin 1 mRNA and protein levels,
      however, CYP2E1 and ADH mRNA and protein levels unchanged. Meanwhile, it
      attenuated the acute alcohol intake-induced decrease in aconitase activity, inner
      mitochondrial membrane potential (Deltapsi), ATP synthase activity, state 3
      respiration rate, respiratory control ratio, and the number of mtDNA. CONCLUSION:
      Pre-endurance training can decrease acute alcohol intake-induced damaged
      mitochondria accumulation and reduced acute alcohol intake-induced mitophagy,
      which built a new balance between mitophagy and damaged mitochondria
      accumulation.

PMID- 26202645
TI  - Procalcitonin as a marker of sepsis in alcoholic hepatitis.
AB  - BACKGROUND: Early diagnosis of sepsis in alcoholic hepatitis is important for
      selecting the appropriate therapy. The role of procalcitonin (PCT) to diagnose
      sepsis in patients with alcoholic hepatitis and systemic inflammatory response
      syndrome (SIRS) is not yet clear. METHODS: All patients admitted with alcoholic
      hepatitis and SIRS underwent measurement of serum PCT and C reactive protein
      (CRP) levels within 24 h of admission. Patients were classified into two groups:
      group 1, alcoholic hepatitis with SIRS alone; group 2, alcoholic hepatitis with
      SIRS and sepsis. The ability of PCT to predict sepsis was evaluated using
      receiver-operating characteristic (ROC) analyses to compare the two groups.
      RESULTS: The study included 11 patients in group 1 and 29 in group 2. All were
      male (median age 42 years; range, 24-65 years). Age, dose and duration of alcohol
      intake, biochemical parameters and median MELD score were not significantly
      different between the two groups. PCT and CRP were significantly higher among
      group 2 than group 1 patients (p < 0.05). ROC analysis showed an AUC of 0.81 (95
      % CI 0.66-0.96) and 0.83 (95 % CI 0.68-0.93) for PCT and CRP, respectively, in
      distinguishing sepsis from SIRS without sepsis. A cutoff level of 0.57 mcg/l for
      PCT (sensitivity 79 %, specificity 82 %) for diagnosing sepsis in patients with
      alcoholic hepatitis and SIRS was comparable to a serum CRP cutoff level of 2.3
      mg/dl (sensitivity 82.0 %, specificity 75 %). CONCLUSION: Serum PCT can be a
      useful marker for diagnosing sepsis in patients with alcoholic hepatitis and SIRS
      and compares favorably with serum CRP levels.

PMID- 26202646
TI  - Psoriatic alopecia.
AB  - Alopecia and other hair abnormalities occurring in patients with psoriasis were
      first recognized over four decades ago, yet psoriatic alopecia is not a well
      known concept among clinicians. Alopecia may be directly related to the psoriasis
      itself, and can affect both the scalp and other parts of the body. On the scalp,
      psoriatic alopecia most commonly affects lesional skin, but may present as a
      generalized telogen effluvium. In most cases, there is regrowth of hair, but in
      rare cases it can cause scarring alopecia. Histological findings include features
      of psoriasis in the interfollicular epithelium, along with perifollicular
      inflammation and atrophy or loss of the sebaceous glands. Late changes include
      destruction of the hair follicle, with perifollicular fibrosis and 'naked' hair
      shafts lying free in the dermis. In addition to the hair loss caused by the
      psoriasis itself, data from population and genetic studies reveal that patients
      with psoriasis are at greater risk of developing alopecia areata. Psoriasis
      treatments may also contribute to hair loss. Application of topical preparations
      may cause hair loss through friction, and many of the systemic treatments used
      for psoriasis can also cause hair problems. Treatment with anti-tumour necrosis
      factor-alpha agents can precipitate de novo psoriasis and subsequent psoriatic
      alopecia. 

PMID- 26202648
TI  - Eradicating H pylori seems to reduce incidence of gastric cancer, review shows.

PMID- 26202647
TI  - Minimizing the evidence-practice gap - a prospective cohort study incorporating
      balance training into pulmonary rehabilitation for individuals with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: We have recently demonstrated the efficacy of balance training in
      addition to Pulmonary Rehabilitation (PR) at improving measures of balance
      associated with an increased risk of falls in individuals with Chronic
      Obstructive Pulmonary Disease (COPD). Few knowledge translation (KT) projects
      have been conducted in rehabilitation settings. The goal of this study was to
      translate lessons learnt from efficacy studies of balance training into a
      sustainable clinical service. METHODS: Health care professionals (HCPs)
      responsible for delivering PR were given an hour of instruction on the principles
      and practical application of balance training and the researchers offered advice
      regarding; prescription, progression and practical demonstrations during the
      first week. Balance training was incorporated three times a week into
      conventional PR programs. Following the program, HCPs participated in a focus
      group exploring their experiences of delivering balance training alongside PR.
      Service users completed satisfaction surveys as well as standardized measures of
      balance control. At six month follow-up, the sustainability of balance training
      was explored. RESULTS: HCPs considered the training to be effective at improving
      balance and the support provided by the researchers was viewed as helpful. HCPs
      identified a number of strategies to facilitate balance training within PR,
      including; training twice a week, incorporating an interval training program for
      everyone enrolled in PR, providing visual aids to training and promoting
      independence by; providing a set program, considering the environment and
      initiating a home-based exercise program early. Nineteen service users completed
      the balance training [ten male mean (SD) age 73 (6) y]. Sixteen patients (84%)
      enjoyed balance training and reported that it helped them with everyday
      activities and 18 (95%) indicated their wish to continue with it. Scores on
      balance measures improved following PR that included balance training (all p <
      0.05). At six month follow-up balance training is being routinely assessed and
      delivered as part of standardised PR. CONCLUSIONS: Implementing balance training
      into PR programs, with support and training for HCPs, is feasible, effective and
      sustainable. TRAIL REGISTRATION: Clinical Trials ID: NCT02080442 (05/03/2014).

PMID- 26202650
TI  - A modular approach for molecular recognition by zinc dipicolinate complexes.
AB  - A series of zinc dipicolinate (2,6-pyridinedicarboxylate; pdc) complexes
      [H2tmbpy][Zn(pdc)2].5H2O () {H2tmbpy = 1,3-bis(4-pyridinium)propane(2+)},
      [H2bpy][Zn(pdc)2].6H2O () {H2bpy = 4,4'-bipyridinium(2+)},
      [H2bpy][Zn(pdc)2].3.5(4np).2H2O () {4np = 4-nitrophenol},
      [H2tmbpy][Zn(pdc)2].4(2,7dhn).3H2O () {2,7dhn = 2,7-dihydroxynaphthalene},
      [H2bpy][Zn(pdc)2].2(2,7dhn).5H2O (), [H2bpy][Zn(pdc)2].2(pyrogl).6H2O () {pyrogl
      = pyrogallol}, and [H2tmbpy][Zn(pdc)2].2(2,6dhn).8H2O () {2,6dhn = 2,6
      dihydroxynaphthalene} were synthesized and characterised. Different packing
      patterns in these complexes arise from differences in the abilities of cations to
      pi-stack with zinc dipicolinate units. In , the planar [H2bpy](2+) moieties are
      pi-stacked with adjacent 4,4'-bipyridinium cations and [Zn(pdc)2](2-) anions,
      whereas in , pi-stacks are formed exclusively between [Zn(pdc)2](2-) moieties. 4
      Nitrophenol can selectively replace the [H2bpy](2+) cations to form adduct , thus
      representing a novel host-guest system for molecular recognition of 4
      nitrophenol. This recognition does not occur upon treatment of 4-nitrophenol with
      which bears a nonplanar [H2tmbpy](2+) cation. Host-guest interactions of
      pyrogallol, 2,6-dihydroxynaphthalene, and 2,7-dihydroxynaphthalene with the
      parent complexes and were studied, resulting in the crystallization of . The
      crystal structures of show that guest organic molecules are accommodated in the
      layers of zinc dipicolinate anions. The formation of different water clusters is
      also discussed. In addition, topological analysis and classification of the H
      bonded patterns driven by strong hydrogen bonds between the [H2bpy](2+) or
      [H2tmbpy](2+) cations and the [Zn(pdc)2](2-) anions, and organic guest molecules
      were carried out. This analysis revealed: (i) discrete 0D dimeric (in and ) or
      tetrameric (in ) motifs with 1M2-1 or 1,3M4-1 topology, respectively, (ii)
      infinite 1D zigzag chains with 2C1 topology in , and (iii) infinite 2D layers
      with the hcb [Shubnikov hexagonal plane net/(6,3)] topology in . 

PMID- 26202651
TI  - Influence of beta-blockers on endothelial function: A meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Endothelial dysfunction (ED) frequently precedes cardiovascular
      diseases (CVD) and is a well-established risk factor of major adverse cardiac
      events. Beta-blockers are the fundamental drugs used in CVD treatment. METHODS: A
      systematic literature search for randomized controlled trials investigating
      influence of beta-blockers on endothelial function assessed by flow-mediated
      dilation (FMD) was performed in the PubMed and Cochrane Databases. RESULTS:
      Sixteen full-text studies involving a total of 1,273 patients were included in
      the final analysis. The mean age of participating patients ranged from 44.9 to
      63.2 years, the follow-up duration from 1 to 12 months. The comparison of FMD
      change between the beta-blockers and placebo groups showed a statistically
      significant effect of beta-blockers on endothelial function (mean difference [MD]
      0.83; 95% confidence interval [CI] 0.11-1.55; p = 0.02). Third generation beta
      blockers improved FMD in a statistically significant manner compared with second
      generation beta-blockers (MD 1.65; 95% CI 0.17-3.11; p = 0.03). Beta-blockers
      gave an FMD change similar to that obtained with angiotensin receptor blockers
      (ARB), calcium channel blockers (CCB) or hydrochlorothiazide. The FMD value in
      the beta-blocker group was significantly lower compared with the group treated
      with angiotensin converting enzyme inhibitors (ACEI) (MD -0.79; 95% CI -1.37-(
      0.21); p = 0.008) and higher than in the ivabradine group (1.6 +/- 3.61 vs -0.3
      +/- 1.66; p = 0.02). CONCLUSIONS: Beta-blockers improve the endothelial function
      compared with placebo. More-over, third generation beta-blockers improve FMD
      values significantly better than the second generation ones. Beta-blockers had
      similar effect on endothelial function as did ARB, CCB or diuretics. However, the
      beneficial effect of beta-blockers was lower when confronted with ACEI.

PMID- 26202652
TI  - Predictors of early and late left atrial tachycardia and left atrial flutter
      after catheter ablation of atrial fibrillation: long-term follow-up.
AB  - BACKGROUND: The aim of the study was identification of the predictors of left
      atrial tachycardia and left atrial flutter (LATAFL) after radiofrequency catheter
      ablation of atrial fibrillation (CAAF). METHODS: We followed 598 patients (71%
      male, 41% paroxysmal AF; median follow-up: 36 months) after a single step-wise
      CAAF procedure. The time to first documented LATAFL lasting longer than 30 s,
      documented in any kind of electrocardiography (ECG), was defined as an end-point.
      RESULTS: A single CAAF procedure resulted in LATAF in 58 (10%) patients.
      Additional lesions were performed in 275 (46%) patients. Early LATAFL recurrence
      (L 3 months since the index procedure) was observed in 11 (2%) patients. Late
      LATAFL (> 3 months) was noted in 47 (8%) patients. The univariate predictors of
      LATAFL recurrence were: type of AF (p = 0.003), the size of LA (p = 0.002) and
      the type of procedure (p = 0.0001). The identified single independent predictors
      of LATAFL recurrence were enlarged LA (p = 0.001) and mul-tiple (>= 2) additional
      lesions performed during the index procedure (p < 0.0001). CONCLUSIONS: Higher
      rate of LATAFL recurrence was observed in patients with non-paroxysmal AF,
      enlarged LA and any additional lesions performed. Two independent predictors of
      LATAFL recurrence after CAAF were: the enlarged LA and multiple (>= 2) additional
      lesions performed during the index procedure.

PMID- 26202653
TI  - Transaortic transcatheter aortic valve implantation: Results of the Polish arm of
      the ROUTE registry.
AB  - BACKGROUND: Transaortic (TAo) transcatheter aortic valve implantation (TAVI) is
      an alter-native approach in patients considered to be at high risk for classical
      open surgery with poor peripheral vessel access. The purpose of this study was to
      determine the feasibility of using TAo access for TAVI procedures employing the
      Edwards SAPIEN transcatheter heart valve. The primary objective was to determine
      overall 30-day mortality. METHODS: A total of 32 patients with severe aortic
      valve stenosis underwent TAo-TAVI using Edwards SAPIEN bioprostheses.
      Postoperative results were collected according to the Registry of the Utilization
      Of the TAo-TAVI approach using the Edwards SAPIEN Valve (ROUTE) study protocol.
      Complications were assessed using Valve Academic Research Consortium- 2 (VARC-2)
      criteria. RESULTS: The mean age of the population was 80.9 +/- 5.2 years, with
      53.1% being female. All patients received either the SAPIEN XT or the SAPIEN 3
      bioprosthesis (Edwards Lifesciences). Device success was achieved in 100% of
      cases. One (3.25%) patient subsequently suffered an aortic dissection and
      required ascending aorta replacement. Paravalvular leakage was absent or mild in
      26 (81%) patients, and moderate in 6 (19%) patients. Other complications included
      permanent pacemaker implantation in 2 (6.5%), and transient post operative
      delirium in 2 (6.5%) patients. The total hospital stay was 6.7 +/- 2.4 days. New
      York Heart Association class decreased significantly on follow-up. Thirty-day
      mortality rate was 2 (6.5%) patients. CONCLUSIONS: Use of TAo access for TAVI
      procedures has a reasonable clinical outcome and is a safe alternative to the
      transfemoral and transapical approaches, especially for patients with high-risk
      peripheral vessel access.

PMID- 26202654
TI  - Contemporary evaluation of the causes of cardiac tamponade: Acute and long-term
      outcomes.
AB  - BACKGROUND: Cardiac tamponade is a life-threatening state that complicates
      various medical conditions. The contemporary interventional era may have led to
      changes in clinical characteristics, causes and outcomes of cardiac tamponade.
      METHODS: We investigated all patients diagnosed with cardiac tamponade, based on
      clinical and echocardiographic findings, at a single medical center between the
      years 2000 and 2013. Data on medical history, index hospitalizations, pericardial
      fluid etiologies, and acute and long-term outcomes were collected. RESULTS:
      Cardiac tamponade was observed in 83 patients (52% females). Major etiologies
      included complications of percutaneous cardiac interventions (36%) and
      malignancies (primarily lung cancer; 23%), infectious/inflammatory causes (15%)
      and mechanical complications of myocardial infarction (12%). Sixteen (19%)
      patients died during the index hospitalization. Acute presentation of symptoms
      and lower quantity of effusion were associated with in-hospital mortality (p =
      0.045 and p = 0.007). Tamponade secondary to malignancy was associated with the
      most substantial increment in post-discharge mortality (from 16% in-hospital to
      68% 1-year mortality). During the mean follow-up of 45 months, 39 (45%) patients
      died. Malignancies, mechanical complications of myocardial infarction and
      bleeding/coagulation abnormalities were etiologies associated with poor survival
      (80% mortality during follow-up). Tamponade secondary to complications of
      percutaneous cardiac interventions or infectious/inflammatory causes were
      associated with significantly lower mortality (28% and 17%; log rank p < 0.001).
      CONCLUSIONS: In a contemporary cohort, complications of percutaneous cardiac
      intervention replaced malignant diseases as the leading cause of cardiac
      tamponade. Nevertheless, these iatrogenic complications were associated with a
      relatively favorable outcome compared to tamponade induced by complications of
      myocardial infarction, coagulation abnormalities and malignant diseases.

PMID- 26202655
TI  - Number of severe bleeding complications according to classification used: Is
      unified classification of bleeding complications really necessary?
AB  - BACKGROUND: To compare the number of severe periprocedural bleeding complications
      from the total number of bleeding complications associated with diagnostic
      selective coronary angiography or percutaneous coronary intervention (PCI) when
      using different classifications (TIMI, GUSTO, PLATO, BARC) and to relate these
      classifications to real hemodynamic status of evaluated patients. METHODS: We
      analyzed data from 106 patients who underwent invasive procedure for ischemic
      heart disease (selective coronary angiography/PCI) and suffered from any type of
      bleeding complication. RESULTS: The number of bleeding according to impacts on
      hemodynamic status and consequent treatment shows that 54.7% of all bleedings did
      not need any specific therapy. Bleeding leading to death, hemorrhagic shock,
      hemodynamic instability, administration of blood transfusion, surgical procedure
      and local treatment occurred in 6.6%, 1.9%, 5.7%, 14.2%, 2.8%, and 14.2%,
      respectively. The results comparing bleeding classifications demonstrate that the
      rate of severe bleeding complications may increase up to 4 times when different
      classifications are used on the same group of patients (TIMI 9.4%, GUSTO 15.1%,
      PLATO 39.2% and BARC 35.9%). The power of association between severe bleeding
      determined by these classifications and real hemodynamic compromise using
      Kendall's tau-c correlation is -0.4106 (95% CI -0.599 to -0.222), -0.5355 (95% CI
      -0.718 to -0.353), -0.5513 (95% CI -0.729 to -0.374) and -0.7552 (95% CI -0.897
      to -0.612) for TIMI, GUSTO, PLATO and BARC, respectively. CONCLUSIONS: The data
      show significant dependence of percentage of severe periprocedural bleeding
      complications on selected classification. The strongest association between
      severe bleeding and real hemodynamic status was found for BARC classification as
      this classification seems to be promising for future general use.

PMID- 26202656
TI  - Evaluation of atrial electromechanical conduction delay in case of
      hemodynamically insignificant rheumatic heart disease: A tissue Doppler study.
AB  - BACKGROUND: Atrial electromechanical delay (AEMD) that reflects delayed
      conduction may show us the clinical reflection of pathological changes in the
      atria. The main objective of the present study is to investigate AEMD in patients
      who had previous rheumatic carditis but without hemodynamically significant
      valvular disease. METHODS: A total of 40 patients, previously diagnosed as
      rheumatic carditis but without significant valvular stenosis/regurgitation and
      atrial enlargement; and 39 age- and-sex matched controls were enrolled for the
      present study. Parameters of AEMD (lateral mitral annulus electromechanical
      delay, septal mitral annulus electromechanical delay and lateral tricuspid
      annulus electromechanical delay) were measured with tissue Doppler
      echocardiography and left intra-atrial and inter-atrial conduction times were
      calculated accordingly. A 24h ambulatory Holter monitoring was used in both
      groups to detect atrial fibrillation episodes and quantify atrial extrasystoles.
      RESULTS: Parameters of AEMD, including left intra-atrial and inter-atrial
      conduction times of subjects in the study group were longer compared to the
      control group (23.7 +/- 7.0 vs. 18.3 +/- 6.2). CONCLUSIONS: Increased AEMD is
      observed in patients with previous rheumatic carditis and no significant valvular
      stenosis/regurgitation and atrial enlargement, which may partly explain the
      increased incidence of atrial fibrillation observed in these patients.

PMID- 26202657
TI  - Fragmented QRS complexes are associated with left ventricular systolic and
      diastolic dysfunctions in patients with metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome (MetS) is found to be associated with
      deterioration of the left ventricular (LV) systolic and diastolic functions. One
      of the factors for this impairment is myocardial fibrosis. Fragmented QRS (fQRS)
      complexes are found to be associated with myocardial fibrosis. The aim of the
      study was to evaluate if the presence of fQRS on electrocardiogram (ECG) can
      detect pronounced impairment in the LV systolic and diastolic functions in MetS
      patients. METHODS: The study included 111 (mean age 47 +/- 9, 49.5% male) MetS
      patients and 96 (mean age 45 +/- 9, 58.3% male) control subjects without MetS.
      ECG was evaluated for the presence of fQRS. Each patient underwent conventional
      echocardiography and tissue Doppler imaging. RESULTS: Fragmented QRS was more
      common among MetS patients (26.1% vs. 14.6%, p = 0.041). MetS was associated with
      subclinical LV systolic and LV diastolic dysfunctions. In subgroup analyses of
      MetS patients, the presence of fQRS on ECG had a higher E/E' ratio and lower E'
      velocity, indicating pronounced diastolic dysfunction, as well as lower
      isovolumic acceleration(IVA), indicating profound subclinical LV systolic
      dysfunction. E/E' ratio and IVA were independent predictors of fQRS presence in
      patients with MetS. CONCLUSIONS: Fragmented QRS is more common among MetS
      patients compared to non-MetS patients. The presence of fQRS is associated with
      pronounced subclinical LV systolic and diastolic dysfunctions in MetS patients.

PMID- 26202659
TI  - Increased frequencies of the killer immunoglobulin-like receptor genes KIR2DL2
      and KIR2DS2 are associated with neuroblastoma.
AB  - Neuroblastoma is the most common extra-cranial solid tumour in children. Natural
      killer (NK) cells are innate lymphocytes that are known to mediate the direct
      cytotoxicity of neuroblastoma tumour cells. Natural variation in the highly
      polymorphic killer immunoglobulin-like receptors (KIR) and their cognate human
      leukocyte antigen (HLA) class I ligands results in considerable diversity in NK
      cell function. As the early onset of neuroblastoma suggests the contribution of
      genetic factors, we investigated if individual KIR genes, combined KIR gene
      haplotypes or compound KIR-HLA ligand genotypes could influence susceptibility to
      neuroblastoma. Genotype analysis of the KIR genes as well as their three major
      HLA class I ligand groups, HLA-C1, HLA-C2 and HLA-Bw4, was carried out in a
      cohort of 201 neuroblastoma patients compared with 240 healthy control subjects
      using polymerase chain reaction with sequence-specific primers. We found a
      significant increase in the frequency of KIR2DL2 (P = 0.019) as well as KIR2DS2
      (P = 0.008) in patients with neuroblastoma compared with the healthy control
      group. While the incidence of the least inhibitory compound KIR-HLA-C genotype,
      KIR2DL3 in the presence of HLA-C1 was slightly reduced in neuroblastoma patients,
      this did not reach statistical significance (P = 0.069). In summary, while KIR
      HLA compound genotypes have previously been implicated in predicting treatment
      outcomes in neuroblastoma, here we show that the presence of the individual KIR
      genes, KIR2DL2 and KIR2DS2, irrespective of HLA-C genotype is associated with the
      onset of this embryonal malignancy.

PMID- 26202658
TI  - Getting it right! Enhancing youth involvement in mental health research.
AB  - BACKGROUND: Few studies relating to youth mental health have actively involved
      young people in the design and conduct of research. AIMS: This qualitative study
      explores the perceptions of young people about involving them in mental health
      research. METHOD: An opportunistic sample of eight young people (aged 14-24
      years) from non-statutory mental health organizations was interviewed. Interviews
      were transcribed verbatim, and inductive thematic analysis was conducted.
      RESULTS: Six key themes emerged reflecting a desire for young people to have the
      opportunity to actively contribute to every stage of the research process.
      Meaningful research involvement was perceived as offering opportunities to
      develop personal skills, contribute to making a difference and ensuring research
      projects were more relevant. CONCLUSIONS: Young people with an active interest in
      mental health promotion demonstrate a desire to be involved in research with
      training in research methods likely to facilitate this process. Researchers need
      training on how best to actively and meaningfully involve young people in mental
      health research.

PMID- 26202660
TI  - A technical report on ultrasound-guided scapulocostal syndrome injection.
AB  - INTRODUCTION: We describe a case report and technique for using an ultrasound
      scanner and a linear transducer to guide serratus posterior superior (SPS) muscle
      injection. A 43-year-old female presented with chronic pain centered under the
      right upper portion of her scapula impacting her activities of daily living.
      METHODS AND MATERIALS: For the ultrasound-guided SPS muscle injection, the
      patient was placed in the prone position. The transducer was oriented in a
      transverse orientation at the level of the C6-T1 vertebrae. Here the SPS muscle
      attaches to the lower portion of the ligament nuchae and the intervening
      interspinous ligaments. The muscle fibers run inferiorly and laterally to attach
      to the 2nd-5th ribs which were identified along with the lateral portion of the
      serratus posterior superior muscle which is covered by the scapula. Real-time
      imaging was used to direct a spinal needle into the trigger points of the SPS
      muscle, where solution was injected under direct vision. The patient's pain
      symptoms improved significantly. CONCLUSION: Serratus posterior superior
      injection can confirm a diagnosis of scapulocostal syndrome and be
      therapeutically beneficial.

PMID- 26202661
TI  - Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis
      of eighteen prospective cohort studies.
AB  - Epidemiological studies have demonstrated inconsistent associations between tea
      consumption and mortality of all cancers, CVD and all causes. To obtain
      quantitative overall estimates, we conducted a dose-response meta-analysis of
      prospective cohort studies. A literature search in PubMed and Embase up to April
      2015 was conducted for all relevant papers published. Random-effects models were
      used to calculate pooled relative risks (RR) with 95 % CI. In eighteen
      prospective studies, there were 12 221, 11 306 and 55 528 deaths from all
      cancers, CVD and all causes, respectively. For all cancer mortality, the summary
      RR for the highest v. lowest category of green tea and black tea consumption were
      1.06 (95 % CI 0.98, 1.15) and 0.79 (95 % CI 0.65, 0.97), respectively. For CVD
      mortality, the summary RR for the highest v. lowest category of green tea and
      black tea consumption were 0.67 (95 % CI 0.46, 0.96) and 0.88 (95 % CI 0.77,
      1.01), respectively. For all-cause mortality, the summary RR for the highest v.
      lowest category of green tea and black tea consumption were 0.80 (95 % CI 0.68,
      0.93) and 0.90 (95 % CI 0.83, 0.98), respectively. The dose-response analysis
      indicated that one cup per d increment of green tea consumption was associated
      with 5 % lower risk of CVD mortality and with 4 % lower risk of all-cause
      mortality. Green tea consumption was significantly inversely associated with CVD
      and all-cause mortality, whereas black tea consumption was significantly
      inversely associated with all cancer and all-cause mortality. 

PMID- 26202662
TI  - Outbreak of Marek's disease in a vaccinated broiler breeding flock during its
      peak egg-laying period in China.
AB  - BACKGROUND: Outbreaks of Marek's disease (MD), caused by Marek's disease virus
      (MDV), primarily occur in 10-12-week-old hens. CASE PRESENTATION: We report a
      case of MD in a breeding flock of 24-30-week-old vaccinated broilers in China.
      The clinical signs in the affected chickens appeared at 24 weeks, and the
      incidence of tumours peaked at 30 weeks. The morbidity and mortality of the hens
      were 5 % and 80 %, respectively. Hematoxylin-eosin staining of the tissues showed
      the typical characteristics of MD. MDV infection was confirmed in the hens with
      an agar gel diffusion precipitation assay for the MD antigen in the feather
      follicle epithelium. An MDV strain, designated AH1410, was isolated from the
      blood lymphocytes. Sequence analyses of the pp38, meq, and gB genes revealed that
      strain AH1410 had molecular features consistent with a virulent, previously
      identified MDV. CONCLUSION: Our data provide evidence that not only is MDV
      becoming more virulent, but that the period of its onset in chickens is
      expanding. These findings provide the basis the molecular surveillance and
      further study of virulent MDV mutants and control strategies for MD in China.

PMID- 26202663
TI  - Deliquescence: Hygroscopicity of Water-Soluble Crystalline Solids.
AB  - A thermodynamic approach to the description of hygroscopic properties of crystal
      soluble solids is introduced. Isotherms of water vapor sorption by a pure
      substance and the products with a heterogeneous or homogeneous impurity are
      compared. Solubility diagrams of substances in water are used to evaluate the
      influence of impurities on the hygroscopic properties of the products. Evidence
      demonstrates that water vapor sorption by a chemical product below the
      hygroscopic point of a basic component is determined by heterogeneous impurities.
      The introduction of the term "a hygroscopically pure substance" removes
      inconsistencies between the experimental results related to water vapor sorption
      and abstract theorems. The paper discusses relevant publications, concerning
      hygroscopicity of soluble substances, where the impurities are ignored resulting
      in procedural and theoretical errors.

PMID- 26202664
TI  - Cyanobacterial secondary metabolites mediate interspecies-intraspecies
      communication in the water body.

PMID- 26202665
TI  - Hyponatremia: a significant factor in a poor prognosis for cirrhosis with Child
      A/B after variceal eradication.
AB  - BACKGROUND: To identify prognostic factors prospectively in cirrhosis after the
      eradication of esophageal varices (EV). METHODS: There were 52 cirrhosis patients
      (Child-Pugh A 24, B 28) who showed the eradication of EV after the endoscopic
      sclerotherapy (median observation period, 25.5 months). RESULTS: Eighteen
      patients showed a recurrence of EV. The cumulative overall survival rate was
      92.2% at 1 year, 70.9% at 3 years, and 47.2% at 5 years. Univariate analysis
      showed that serum sodium concentration (hazard ratio [HR] 0.724, P = 0.0006),
      serum aspartate transaminase (HR 1.019, P = 0.0075), serum alanine transaminase
      (HR 1.025, P = 0.0239), and serum creatinine (HR 11.311, P = 0.044) levels before
      treatment were significant factors for a poor prognosis. Multivariate analysis
      revealed that serum sodium concentration (HR 0.711, P = 0.0022) was the only
      significant factor. The cumulative survival rate was lower in patients with
      hyponatremia (<135 mEq/l, a best cut-off value; 83.3% at 1 year, and 33.3% at 3
      years), than in those without (93.3% at 1 year, 77.3% at 3 years and 47.2% at 5
      years). CONCLUSIONS: Pre-treatment hyponatremia is a significant prognostic
      factor in cirrhosis with Child A/B after the eradication of EV by the endoscopic
      sclerotherapy.

PMID- 26202666
TI  - The role of clinical genomic testing in diagnosis and discovery of pathogenic
      mutations.
AB  - Next-generation sequencing in clinical practice allows for a critical review of
      the literature to evaluate disease relatedness of specific genes and
      pathogenicity of individual mutations, while providing an important discovery
      tool for new disease genes and disease-causing mutations. Data obtained from
      large panels, whole exome or whole genome sequencing, performed for
      constitutional or cancer cases, need to be managed in a transparent, yet powerful
      analytical framework. Assessment of reported pathogenic potential of a variant or
      disease association of a gene requires careful consideration of population allele
      frequency, variant data from parents, and precise, yet concise phenotypic
      description of the entire family and other individuals or families that have the
      same variant. The full potential for discovery can only be realized if there is
      data sharing between clinicians performing the interpretation worldwide and
      structural biologists, analytical chemists and cell biologists interested and
      knowledgeable of the structure and function of the genes involved. 

PMID- 26202667
TI  - The clinical relevance of circulating, exosomal miRNAs as biomarkers for cancer.
AB  - In cancer, deregulated expression levels of miRNAs are associated with
      tumorigenesis, tumor progression, metastasis and drug resistance. Apart from
      their release by apoptotic and necrotic cells, miRNAs can also be actively
      secreted into the blood circulation by exosomes. Exosomal miRNAs are thought to
      play an important role in cell-to-cell communication. Based on their biological
      functions and the possibility of quantifying miRNAs in patient blood in real
      time, these small non-coding RNA molecules may be a new promising class of
      potential non-invasive biomarkers. Screening of these liquid biopsies may provide
      information on target molecules of miRNAs and aberrant signaling pathways that
      can be blocked by a chosen targeted therapy. Consequently, therapy-associated
      modulations may facilitate treatment decisions. The present article discusses the
      potential clinical use of exosomal miRNAs as diagnostic and prognostic tumor
      markers. The emerging role of exosomes as a mediator of cell-to-cell signaling,
      to transfer miRNAs between cells, is also discussed. 

PMID- 26202668
TI  - Trajectories of self-rated health in the last 15 years of life by cause of death.
AB  - Poor self-rated health is associated with increased risk of mortality, but no
      previous study has examined how long-term trajectories of self-rated health
      differ among people at risk of subsequent death compared to those who survive.
      Data were drawn from French occupational cohort (the GAZEL study, 1989-2010).
      This nested case-control study included 915 deceased men and women and 2578
      controls matched for sex, baseline age, occupational grade and marital status.
      Self-rated health was measured annually and dichotomized into good versus poor
      health. Trajectories of poor self-rated health up to 15 years were compared among
      people who subsequently died to those who survived. Participants contributed to
      an average 10.3 repeated assessments of self-rated health. Repeated-measures log
      binomial regression analysis with generalized estimating equations showed an
      increased prevalence of poor self-rated health in cases 13-15 years prior to
      death from ischemic and other cardiovascular disease [multivariable-adjusted risk
      ratio 2.06, 95 % confidence interval (CI) 1.55-2.75], non-smoking-related cancers
      (1.57, 95 % CI 1.30-1.89), and suicide (1.78, 95 % CI 1.00-3.16). Prior to death
      from ischemic and other cardiovascular disease, increased rates of poor self
      rated health were evident even among persons who were free of cardiovascular
      diseases (2.05, 95 % CI 1.50-2.78). In conclusion, perceptions of health diverged
      between the surviving controls and the deceased already 15 years prior to death.
      For cardiovascular mortality, decline in self-rated health started before
      diagnosis of the disease leading to death. The findings suggest that declining
      self-rated health might capture pathological changes before and beyond the
      disease diagnosis.

PMID- 26202669
TI  - Service integration: opportunities to expand access to antiretroviral therapy for
      people who inject drugs in Tanzania.

PMID- 26202670
TI  - Cerebellar fMRI Activation Increases with Increasing Working Memory Demands.
AB  - The aim of the present study was to explore cerebellar contributions to the
      central executive in n-back working memory tasks using 7-T functional magnetic
      imaging (fMRI). We hypothesized that cerebellar activation increased with
      increasing working memory demands. Activations of the cerebellar cortex and
      dentate nuclei were compared between 0-back (serving as a motor control task), 1
      back, and 2-back working memory tasks for both verbal and abstract modalities. A
      block design was used. Data of 27 participants (mean age 26.6 +/- 3.8 years,
      female/male 12:15) were included in group statistical analysis. We observed that
      cerebellar cortical activations increased with higher central executive demands
      in n-back tasks independent of task modality. As confirmed by subtraction
      analyses, additional bilateral activations following higher executive demands
      were found primarily in four distinct cerebellar areas: (i) the border region of
      lobule VI and crus I, (ii) inferior parts of the lateral cerebellum (lobules crus
      II, VIIb, VIII, IX), (iii) posterior parts of the paravermal cerebellar cortex
      (lobules VI, crus I, crus II), and (iv) the inferior vermis (lobules VI, VIIb,
      VIII, IX). Dentate activations were observed for both verbal and abstract
      modalities. Task-related increases were less robust and detected for the verbal n
      back tasks only. These results provide further evidence that the cerebellum
      participates in an amodal bilateral neuronal network representing the central
      executive during working memory n-back tasks. 

PMID- 26202671
TI  - More Falls in Cerebellar Ataxia When Standing on a Slow Up-Moving Tilt of the
      Support Surface.
AB  - We investigated how subjects with cerebellar ataxia (CA) adapt their postural
      stability and alignment to a slow and small tilt of the support surface allowing
      for online postural corrections. Eight subjects with CA and eight age- and gender
      matched healthy control subjects participated in the study. Subjects stood eyes
      closed for 1 min after which the support surface was tilted 5 degrees  toes-up at
      a ramp velocity of 1 degrees /s. The toes-up position was held for 2.5 min after
      which the surface rotated back down to level with identical tilt characteristics.
      As reflected by the large number of falls, subjects with CA had marked difficulty
      adapting their posture to the up-moving incline in contrast to control subjects.
      Subjects with CA who lost their balance had faster trunk velocity and excessive
      backward trunk reorientation beginning within the first second after onset of the
      tilting surface. In contrast, the down-moving tilt to level did not result in
      instability in CA subjects. These results suggest that instability and falls
      associated with CA derive from an inability to maintain trunk orientation to
      vertical while standing on a slow-moving or unstable surface. This study
      underscores the importance of the cerebellum in the online sensory control of the
      upper body orientation during small amplitude and slow velocity movements of the
      support surface.

PMID- 26202672
TI  - Cerebellar Clustering and Functional Connectivity During Pain Processing.
AB  - The cerebellum has been traditionally considered a sensory-motor structure, but
      more recently has been related to other cognitive and affective functions.
      Previous research and meta-analytic studies suggested that it could be involved
      in pain processing. Our aim was to distinguish the functional networks subserved
      by the cerebellum during pain processing. We used functional magnetic resonance
      imaging (fMRI) on 12 subjects undergoing mechanical pain stimulation and resting
      state acquisition. For the analysis of data, we used fuzzy c-mean to cluster
      cerebellar activity of each participant during nociception. The mean time courses
      of the clusters were used as regressors in a general linear model (GLM) analysis
      to explore brain functional connectivity (FC) of the cerebellar clusters. We
      compared our results with the resting state FC of the same cluster and explored
      with meta-analysis the behavior profile of the FC networks. We identified three
      significant clusters: cluster V, involving the culmen and quadrangular lobules
      (vermis IV-V, hemispheres IV-V-VI); cluster VI, involving the posterior
      quadrangular lobule and superior semilunar lobule (hemisphere VI, crus 1, crus
      2), and cluster VII, involving the inferior semilunar lobule (VIIb, crus1, crus
      2). Cluster V was more connected during pain with sensory-motor areas, cluster VI
      with cognitive areas, and cluster VII with emotional areas. Our results indicate
      that during the application of mechanical punctate stimuli, the cerebellum is not
      only involved in sensory functions but also with areas typically associated with
      cognitive and affective functions. Cerebellum seems to be involved in various
      aspects of nociception, reflecting the multidimensionality of pain perception. 

PMID- 26202673
TI  - Operationalising emergency care delivery in sub-Saharan Africa: consensus-based
      recommendations for healthcare facilities.
AB  - A major barrier to successful integration of acute care into health systems is
      the lack of consensus on the essential components of emergency care within
      resource-limited environments. The 2013 African Federation of Emergency Medicine
      Consensus Conference was convened to address the growing need for practical
      solutions to further implementation of emergency care in sub-Saharan Africa. Over
      40 participants from 15 countries participated in the working group that focused
      on emergency care delivery at health facilities. Using the well-established
      approach developed in the WHO's Monitoring Emergency Obstetric Care, the
      workgroup identified the essential services delivered-signal functions-associated
      with each emergency care sentinel condition. Levels of emergency care were
      assigned based on the expected capacity of the facility to perform signal
      functions, and the necessary human, equipment and infrastructure resources
      identified. These consensus-based recommendations provide the foundation for
      objective facility capacity assessment in developing emergency health systems
      that can bolster strategic planning as well as facilitate monitoring and
      evaluation of service delivery. 

PMID- 26202674
TI  - Saving the critically ill trauma patient.

PMID- 26202675
TI  - The value of signal peptide-CUB-EGF domain-containing protein-1 (SCUBE1) in the
      diagnosis of pulmonary embolism: a preliminary study.
AB  - OBJECTIVES: The diagnosis of pulmonary embolism (PE) in the emergency department
      still poses difficulties because symptoms and signs are nonspecific. There is a
      need for more reliable noninvasive diagnostic tests to support clinical suspicion
      before the costly invasive procedures with complication risks still used in the
      diagnosis of PE. Signal peptide-CUB (complement C1r/C1s, Uegf, and Bmp1)-EGF
      (epidermal growth factor) domain-containing protein 1 (SCUBE1) is a novel,
      secreted cell surface protein expressed during early embryogenesis. The goal of
      this study was to compare the SCUBE1 levels between PE patients and healthy
      subjects and also investigate the value of SCUBE1 in the diagnosis of PE.
      METHODS: Eleven patients diagnosed with PE using spiral computerized tomographic
      pulmonary angiography were included in the study. A control group of 23 age
      matched, healthy volunteers served as a reference for biochemical parameters.
      RESULTS: Mean (+/-SD) SCUBE1 levels were 72.0 (+/-32.6) ng/mL in the patients
      with PE and 31.4 (+/-13.8) ng/mL in the control group. SCUBE1 levels were
      significantly higher in the patients with PE (p = 0.001). Receiver operating
      characteristic (ROC) curve analysis was performed to determine cutoff thresholds
      in discriminating between PE and control group plasma SCUBE1 levels. Area under
      the ROC for that purpose was 0.862 (95% confidence interval [CI] = 0.70 to 1). A
      SCUBE1 cutoff point in patients with PE > 46 ng/mL had specificity and
      sensitivity of 91% (95% CI = 0.70% to 0.98%) and 82% (95% CI = 0.48% to 0.97%),
      respectively. CONCLUSIONS: This preliminary study suggests that plasma SCUBE1
      values have a good level of specificity for PE and may be of use in the diagnosis
      of PE. Further studies involving larger case series and also clinical studies are
      needed to corroborate these findings.

PMID- 26202676
TI  - Galectin-3 Modulates Experimental Colitis.
AB  - BACKGROUND: We recently identified galectin-3 (gal-3) as a new and strong
      fibroblast activator produced by colonic epithelial cells. Very little is known
      about the influence of gal-3 in inflammatory bowel disease. We, therefore,
      investigated the impact of gal-3 on dextran sodium sulfate (DSS)-induced colitis
      in a mouse model. METHODS: Colonic lamina propria fibroblasts of healthy controls
      were used for co-incubation studies of gal-3 with gal-1, TGF-beta1, IFNgamma, IL
      4 and IL-10. Acute and chronic DSS colitis was induced by 3% DSS in drinking
      water in female Balb/c mice weighing 20-22 g. Recombinant gal-3 was expressed by
      the pET vector system and used for a 5-day treatment in different concentrations
      intraperitoneally. The distal third of the colon was used for histologic
      analysis. Colonic cytokine expression was determined by quantitative RT-PCR.
      RESULTS: In vitro, gal-3 induced IL-8 secretion was significantly reduced by co
      incubation with IL-10 (5 ng/ml) and IL-4 (10 ng/ml). Acute DSS-induced colitis
      was ameliorated by gal-3 treatment as indicated by increased colonic length and
      reduced weight loss compared to that of controls. In acute and chronic colitis,
      gal-3 treatment resulted in a significant suppression of colonic IL-6.
      CONCLUSION: Gal-3 significantly reduces inflammation in acute and chronic DSS
      colitis in mice indicating a potential role in intestinal inflammation.

PMID- 26202677
TI  - Dielectrophoresis-Mediated Electrodeformation as a Means of Determining
      Individual Platelet Stiffness.
AB  - Platelets, essential for hemostasis, are easily activated via biochemical and
      mechanical stimuli. Cell stiffness is a vital parameter modulating the mechano
      transduction of exogenous mechanical stimuli. While methods exist to measure cell
      stiffness, no ready method exists for measuring platelet stiffness that is both
      minimally-contacting, imparting minimal exogenous force and non-activating. We
      developed a minimal-contact methodology capable of trapping and measuring the
      stiffness of individual platelets utilizing dielectrophoresis (DEP)-mediated
      electrodeformation. Parametric studies demonstrate a non-uniform electric field
      in the MHz frequency range (0.2-20 MHz) is required for generating effective DEP
      forces on platelets, suspended in isotonic buffer with conductivity ~100-200
      MUS/cm. A nano-Newton DEP force (0.125-4.5 nN) was demonstrated to be essential
      for platelet electrodeformation, which could be generated with an electric field
      with strength of 1.5-9 V/MUm. Young's moduli of platelets were calculated using a
      Maxwell stress tensor model and stress-deformation relationship. Platelet
      stiffness was determined to be in the range of 3.5 +/- 1.4 and 8.5 +/- 1.5 kPa
      for resting and 0.4% paraformaldehyde-treated cells, respectively. The developed
      methodology fills a gap in approaches of measuring individual platelet stiffness,
      free of inadvertent platelet activation, which will facilitate further studies of
      mechanisms involved in mechanically-mediated platelet activation.

PMID- 26202678
TI  - Allelic variants of hexose transporter Hxt3p and hexokinases Hxk1p/Hxk2p in
      strains of Saccharomyces cerevisiae and interspecies hybrids.
AB  - The transport of sugars across the plasma membrane is a critical step in the
      utilization of glucose and fructose by Saccharomyces cerevisiae during must
      fermentations. Variations in the molecular structure of hexose transporters and
      kinases may affect the ability of wine yeast strains to finish sugar
      fermentation, even under stressful wine conditions. In this context, we sequenced
      and compared genes encoding the hexose transporter Hxt3p and the kinases
      Hxk1p/Hxk2p of Saccharomyces strains and interspecies hybrids with different
      industrial usages and regional backgrounds. The Hxt3p primary structure varied in
      a small set of amino acids, which characterized robust yeast strains used for the
      production of sparkling wine or to restart stuck fermentations. In addition,
      interspecies hybrid strains, previously isolated at the end of spontaneous
      fermentations, revealed a common amino acid signature. The location and potential
      influence of the amino acids exchanges is discussed by means of a first modelled
      Hxt3p structure. In comparison, hexokinase genes were more conserved in different
      Saccharomyces strains and hybrids. Thus, molecular variants of the hexose carrier
      Hxt3p, but not of kinases, correlate with different fermentation performances of
      yeast.

PMID- 26202679
TI  - Epithelial-mesenchymal transition and drug resistance in breast cancer (Review).
AB  - Breast cancer is the leading cause of cancer death in women worldwide.
      Insensitivity of tumor cells to drug therapies is an essential reason arousing
      such high mortality. Epithelial-mesenchymal transition (EMT) is defined by the
      loss of epithelial characteristics and the acquisition of a mesenchymal
      phenotype. It is well known that EMT plays an important role in breast cancer
      progression. Recently, mounting evidence has demonstrated involvement of EMT in
      antagonizing chemotherapy in breast cancer. Here, we discuss the biological
      significance and clinical implications of these findings, with an emphasis on
      novel approaches that effectively target EMT to increase the efficacy of
      anticancer therapies. 

PMID- 26202680
TI  - Extending the evaluation of Genia Event task toward knowledge base construction
      and comparison to Gene Regulation Ontology task.
AB  - BACKGROUND: The third edition of the BioNLP Shared Task was held with the grand
      theme "knowledge base construction (KB)". The Genia Event (GE) task was re
      designed and implemented in light of this theme. For its final report, the
      participating systems were evaluated from a perspective of annotation. To further
      explore the grand theme, we extended the evaluation from a perspective of KB
      construction. Also, the Gene Regulation Ontology (GRO) task was newly introduced
      in the third edition. The final evaluation of the participating systems resulted
      in relatively low performance. The reason was attributed to the large size and
      complex semantic representation of the ontology. To investigate potential
      benefits of resource exchange between the presumably similar tasks, we measured
      the overlap between the datasets of the two tasks, and tested whether the dataset
      for one task can be used to enhance performance on the other. RESULTS: We report
      an extended evaluation on all the participating systems in the GE task,
      incoporating a KB perspective. For the evaluation, the final submission of each
      participant was converted to RDF statements, and evaluated using 8 queries that
      were formulated in SPARQL. The results suggest that the evaluation may be
      concluded differently between the two different perspectives, annotation vs. KB.
      We also provide a comparison of the GE and GRO tasks by converting their datasets
      into each other's format. More than 90% of the GE data could be converted into
      the GRO task format, while only half of the GRO data could be mapped to the GE
      task format. The imbalance in conversion indicates that the GRO is a
      comprehensive extension of the GE task ontology. We further used the converted
      GRO data as additional training data for the GE task, which helped improve GE
      task participant system performance. However, the converted GE data did not help
      GRO task participants, due to overfitting and the ontology gap.

PMID- 26202681
TI  - Better reporting for better research: a checklist for reproducibility.

PMID- 26202682
TI  - In silico analysis suggests differential response to bevacizumab and radiation
      combination therapy in newly diagnosed glioblastoma.
AB  - Recently, two phase III studies of bevacizumab, an anti-angiogenic, for newly
      diagnosed glioblastoma (GBM) patients were released. While they were unable to
      statistically significantly demonstrate that bevacizumab in combination with
      other therapies increases the overall survival of GBM patients, there remains a
      question of potential benefits for subpopulations of patients. We use a
      mathematical model of GBM growth to investigate differential benefits of
      combining surgical resection, radiation and bevacizumab across observed tumour
      growth kinetics. The differential hypoxic burden after gross total resection
      (GTR) was assessed along with the change in radiation cell kill from bevacizumab
      induced tissue re-normalization when starting therapy for tumours at different
      diagnostic sizes. Depending on the tumour size at the time of treatment, our
      model predicted that GTR would remove a variable portion of the hypoxic burden
      ranging from 11% to 99.99%. Further, our model predicted that the combination of
      bevacizumab with radiation resulted in an additional cell kill ranging from
      2.6*10(7) to 1.1*10(10) cells. By considering the outcomes given individual
      tumour kinetics, our results indicate that the subpopulation of patients who
      would receive the greatest benefit from bevacizumab and radiation combination
      therapy are those with large, aggressive tumours and who are not eligible for
      GTR. 

PMID- 26202683
TI  - The life story of hydrogen peroxide II: a periodic pH and thermochemical drive
      for the RNA world.
AB  - It is now accepted that primordial non-cellular RNA communities must have been
      subject to a periodic drive in order to replicate and prosper. We have proposed
      the oxidation of thiosulfate by hydrogen peroxide as this drive. This reaction
      system behaves as (i) a thermochemical and (ii) a pH oscillator, and in this
      work, we unify (i) and (ii) for the first time. We report thermally self
      consistent, dynamical simulations in which the system transitions smoothly from
      nearly isothermal pH to fully developed thermo-pH oscillatory regimes. We use
      this oscillator to drive simulated replication of a 39-bp RNA species. Production
      of replicated duplex under thermo-pH drive was significantly enhanced compared
      with that under purely thermochemical drive, effectively allowing longer strands
      to replicate. Longer strands are fitter, with more potential to evolve enzyme
      activity and resist degradation. We affirm that concern over the alleged toxicity
      of hydrogen peroxide to life is largely misplaced in the current context, we
      survey its occurrence in the solar system to motivate its inclusion as a
      biosignature in the search for life on other worlds and highlight that pH
      oscillations in a spatially extended, bounded system manifest as the fundamental
      driving force of life: a proton gradient. 

PMID- 26202684
TI  - An artificial elementary eye with optic flow detection and compositional
      properties.
AB  - We describe a 2 mg artificial elementary eye whose structure and functionality is
      inspired by compound eye ommatidia. Its optical sensitivity and electronic
      architecture are sufficient to generate the required signals for the measurement
      of local optic flow vectors in multiple directions. Multiple elementary eyes can
      be assembled to create a compound vision system of desired shape and curvature
      spanning large fields of view. The system configurability is validated with the
      fabrication of a flexible linear array of artificial elementary eyes capable of
      extracting optic flow over multiple visual directions. 

PMID- 26202685
TI  - Directional, passive liquid transport: the Texas horned lizard as a model for a
      biomimetic 'liquid diode'.
AB  - Moisture-harvesting lizards such as the Texas horned lizard (Iguanidae:
      Phrynosoma cornutum) live in arid regions. Special skin adaptations enable them
      to access water sources such as moist sand and dew: their skin is capable of
      collecting and transporting water directionally by means of a capillary system
      between the scales. This fluid transport is passive, i.e. requires no external
      energy, and directs water preferentially towards the lizard's snout. We show that
      this phenomenon is based on geometric principles, namely on a periodic pattern of
      interconnected half-open capillary channels that narrow and widen. Following a
      biomimetic approach, we used these principles to develop a technical prototype
      design. Building upon the Young-Laplace equation, we derived a theoretical model
      for the local behaviour of the liquid in such capillaries. We present a global
      model for the penetration velocity validated by experimental data. Artificial
      surfaces designed in accordance with this model prevent liquid flow in one
      direction while sustaining it in the other. Such passive directional liquid
      transport could lead to process improvements and reduction of resources in many
      technical applications. 

PMID- 26202686
TI  - Global relationships in fluctuation and response in adaptive evolution.
AB  - Cells change their internal state to adapt to environmental changes, and evolve
      in response to the new conditions. The phenotype changes first via adaptation in
      response to environmental changes, and then through mutational changes in the
      genomic sequence, followed by selection in evolution. Here, we analysed simulated
      adaptive evolution using a simple cell model consisting of thousands of
      intracellular components, and found that the changes in their concentrations by
      adaptation are proportional to those by evolution across all the components,
      where the proportion coefficient between the two agreed well with the change in
      the growth rate of a cell. Furthermore, we demonstrate that the phenotypic
      variance in concentrations of cellular components due to (non-genetic) noise and
      to genomic alternations is proportional across all components. This implies that
      the specific phenotypes that are highly evolvable were already given by non
      genetic fluctuations. These global relationships in cellular states were also
      supported by phenomenological theory based on steady reproduction and
      transcriptome analysis of laboratory evolution in Escherichia coli. These
      findings demonstrate that a possible evolutionary change in phenotypic state is
      highly restricted. Our results provide a basis for the development of a
      quantitative theory of plasticity and robustness in phenotypic evolution. 

PMID- 26202687
TI  - Tumour location adjacent to the ureteric orifice in primary Ta/T1 bladder cancer
      is predictive of recurrence.
AB  - OBJECTIVE: The aim of this study was to evaluate tumour growth located around the
      ureteric orifice (LUO) at primary diagnosis of Ta/T1 urinary bladder cancer in
      relation to effects on recurrence and progression. MATERIALS AND METHODS:
      Clinical and pathological characteristics of patients diagnosed with primary
      Ta/T1 urinary bladder cancer from 1992 to 2007 were recorded prospectively.
      Location of the primary tumour and growth around the ureteric orifice (within 1
      cm) were recorded and correlated with recurrence and progression during further
      follow-up. Hazard ratios (HRs) were estimated using Cox regression with 95%
      confidence intervals (CIs) in both univariate and multivariate analysis. RESULTS:
      The study included 768 evaluable patients with a median follow-up of 60 months.
      Recurrence was observed in 478 patients (62%) and progression in 71 (9%). Growth
      of a primary tumour adjacent to the ureteric orifice was associated with
      recurrence (HR = 1.28, 95% CI = 1.07-1.54) but not progression (HR = 1.04, 95% CI
      = 0.65-1.67). The most common location of the first recurrence was the posterior
      bladder wall (29%). Other locations in the bladder did not predict recurrence or
      progression. Additional factors affecting recurrence were tumour size greater
      than 15 mm, T1 tumour category, multiplicity, malignant or missing/not
      representative bladder wash cytology and surgery performed by residents.
      CONCLUSIONS: A primary tumour located around the ureteric orifice was predictive
      of recurrence, which could be taken into account in future follow-up schedules.

PMID- 26202688
TI  - Expression profile of doublesex/male abnormal-3-related transcription factor-1
      during gonadal sex change in the protogynous wrasse, Halichoeres trimaculatus.
AB  - Sex change in fish involves a dramatic transformation of gonadal tissue and a
      switch in gametogenesis. Doublesex/male abnormal-3-related transcription factor-1
      (DMRT1), encoded by the DMRT1 gene, is involved in testicular differentiation in
      a wide range of vertebrates as well as in sexual differentiation and gonadal sex
      change. In the present study, we investigated changes in the expression of dmrt1
      during artificial gonadal sex change in the three-spot wrasse, Halichoeres
      trimaculatus, by real-time quantitative PCR and immunolocalization, using an anti
      wrasse-Dmrt1 antibody that we prepared. We found that dmrt1 expression was
      predominantly observed in the testes, and that Dmrt1 was expressed in Sertoli
      cells of testes and a few granulosa cells surrounding vitellogenic oocytes of the
      ovary. Additionally, the upregulation of dmrt1 expression was consistent with an
      increase in spermatogenic cyst quantity rather than proliferation of presumptive
      spermatogonia, suggesting that dmrt1 is involved in the progression of
      spermatogenesis during sex change. Changes in the localization of Dmrt1 during
      gonadal sex change further implied that Sertoli cells originate from somatic
      cells adjacent to gonial germ cells during testicular formation in the three-spot
      wrasse.

PMID- 26202689
TI  - Intracerebral hemorrhage patients presenting with normal blood pressure.

PMID- 26202690
TI  - Pre-awakening diastolic hypotension in treated hypertensive patients: prevalence
      and predictors.
AB  - In the pre-awakening hours, diastolic blood pressure (DBP) is normally at its
      lowest, and diastolic hypotension is a risk factor for cardiac ischemia. We
      investigated pre-awakening DBP values and its predictors in treated hypertensive
      patients who underwent ambulatory blood pressure monitoring. The pre-awakening
      period was defined as the 3-h period ending 1 h before awakening (most frequently
      03:00-06:00). In 269 included subjects, office DBP was 86.4+/-12.0 mm Hg, 24-h
      DBP was 78.6+/-9.6 mm Hg, mean pre-awakening DBP was 70.3+/-10.9 mm Hg, and
      trough pre-awakening DBP was 62.5+/-11.2 mm Hg. Half of the patients (51%) had a
      mean pre-awakening DBP <70 mm Hg, and 14% had <60 mm Hg. Trough pre-awakening DBP
      <60 mm Hg was seen in 36% and <50 mm Hg in 12% of patients. Office DBP was the
      most important predictor of mean and trough pre-awakening DBP (both beta=0.4;
      P<0.001), and of pre-awakening DBP <70 mm Hg and <60 mm Hg (both P?0.001).
      Diabetes mellitus was associated with a lower trough pre-awakening DBP (beta=
      3.2; P=0.02). Among variables that failed to independently predict low pre
      awakening DBP were age, a history of vascular disease, and classes and number of
      antihypertensive drugs. We found that many hypertensive patients have low DBP in
      the pre-awakening period. Office DBP is the main predictor of low pre-awakening
      DBP. Further studies are needed to define the prognostic relevance and potential
      risks of low pre-awakening DBP. 

PMID- 26202693
TI  - Low-energy electron diffraction and density functional theory study of potassium
      adsorbed on Pb(1 0 0).
AB  - Alkali metal adsorption systems provide important models for chemisorption. Low
      energy electron diffraction experiments and density functional theory
      calculations were carried out for the adsorption of potassium on Pb(1 0 0). The
      stable structure for all submonolayer coverages was found to be the commensurate
      c(2   *   2) structure, with potassium atoms located in substitutional sites in
      the top substrate layer. This structure is temperature activated and occurs for
      adsorption or annealing of the film above 200 K. This finding is consistent with
      an earlier theory that proposed that for substrates with low energies of vacancy
      formation, substitutional structures can be the most stable. The structural and
      vibrational parameters deduced from the experiment are in agreement with the
      calculated values, and these values fit well into and add to the database of
      alkali metal adsorption properties. 

PMID- 26202692
TI  - Increased plasma neopterin levels are associated with reduced endothelial
      function and arterial elasticity in hypertension.
AB  - Inflammation has been shown to play a pivotal role in the pathogenesis and
      development of hypertensive vascular injury. Neopterin is a novel marker of
      immune activation produced mainly by activated macrophages. Few data are
      available to show the association between neopterin and vascular function in
      hypertension. The present study was designed to investigate the relationship
      between neopterin levels related to arterial stiffness and endothelial function
      in patients with hypertension, and their changes after blood pressure-lowering
      treatment. Twenty-four hypertensive patients and 30 age- and gender-matched
      healthy volunteers were recruited. Plasma neopterin levels were higher in
      hypertensive patients compared with their counterparts (log-neopterin: 0.77+/
      0.18 versus 0.61+/-0.16, P=0.003). Increased neopterin levels were correlated
      with increased brachial-ankle pulse wave velocity (baPWV; control: r=0.659,
      P<0.001; hypertension: r=0.487, P=0.021), and inversely associated with impaired
      brachial flow-mediated dilation (FMD; control: r=-0.735, P<0.001; hypertension:
      r=-0.557, P=0.005). Fifteen hypertensives received 3 months of standard
      antihypertensive treatment. Three months later, their plasma neopterin levels
      decreased (log-neopterin: 0.63+/-0.17 versus 0.50+/-0.19, P=0.001), whereas
      arterial elasticity (baPWV: 1764+/-101 versus 1685+/-96 cm s(-1), P=0.272) and
      endothelial function (FMD: 5.92+/-1.43% versus 7.73+/-1.31%, P<0.05) were
      improved. The decline in neopterin levels was linearly correlated with baPWV
      decrease (r=0.800, P<0.001), FMD improvement (r=0.670, P=0.006) and blood
      pressure reduction (r=0.548, P=0.042). Our present study demonstrated for the
      first time that neopterin is closely correlated with vascular dysfunctions, and
      measurement of plasma neopterin levels might be used as a surrogate biomarker for
      the clinical evaluation of vascular damage and risk stratification of future
      atherosclerotic cardiovascular disease in patients with hypertension.

PMID- 26202694
TI  - Preface.

PMID- 26202691
TI  - Relationship of adiposity and cardiorespiratory fitness with resting blood
      pressure of South African adolescents: the PAHL Study.
AB  - Obesity and low level of cardiorespiratory fitness are associated with high blood
      pressure in both adolescents and adults. The objective of this study was to
      assess the relationship of adiposity and cardiorespiratory fitness with resting
      blood pressure in 14-year-old male and female adolescents. Cross-sectional data
      on 310 adolescents (31.8% boys) from six high schools, who were participating in
      the on-going Physical Activity and Health Longitudinal Study, were collected.
      Height, weight, body mass index (BMI), percentage of body fat, waist
      circumference, waist-to-height ratio, predicted and resting systolic (SBP) and
      diastolic blood pressure (DBP) were assessed according to standard procedures.
      The prevalence of elevated SBP and DBP were 4.9% and 6.5%, respectively. The
      highest prevalence of elevated blood pressure (SBP=10% and DBP=15%) were measured
      in overweight adolescents, who also performed poorly for predicted
      VO(2max)(M=26.66 ml kg(-1 )min(-1)+/-6.44) compared with underweight and normal
      weight adolescents. Multiple regression showed that BMI was positively associated
      with SBP (beta=0.77, P=0.005) and VO(2max) was negatively associated with DBP
      (beta=-0.43, P=0.001). Overweight adolescents presented with a relatively high
      prevalence of elevated blood pressure and poor health-related fitness. Fatness
      and poor cardiorespiratory fitness were positively associated with elevated SBP
      and DBP, respectively. In view of the health implications of these findings,
      strategic interventions are needed to promote obesity-reduction programmes and
      physical activities in adolescents.

PMID- 26202695
TI  - A Comprehensive Inter-Tissue Crosstalk Analysis Underlying Progression and
      Control of Obesity and Diabetes.
AB  - Obesity is a metabolic state associated with excess of positive energy balance.
      While adipose tissues are considered the major contributor for complications
      associated with obesity, they influence a variety of tissues and inflict
      significant metabolic and inflammatory alterations. Unfortunately, the
      communication network between different cell-types responsible for such systemic
      alterations has been largely unexplored. Here we study the inter-tissue crosstalk
      during progression and cure of obesity using multi-tissue gene expression data
      generated through microarray analysis. We used gene expression data sets from 10
      different tissues from mice fed on high-fat-high-sugar diet (HFHSD) at various
      stages of disease development and applied a novel analysis algorithm to deduce
      the tissue crosstalk. We unravel a comprehensive network of inter-tissue
      crosstalk that emerges during progression of obesity leading to inflammation and
      insulin resistance. Many of the crosstalk involved interactions between well
      known modulators of obesity and associated pathology like inflammation. We then
      used similar datasets from mice that in addition to HFHSD were also administered
      with a herbal concoction known to circumvent the effects of HFHSD in the diet
      induced model of obesity in mice. We propose, the analysis presented here could
      be applied to understand systemic details of several chronic diseases. 

PMID- 26202696
TI  - The SAD-MEN questionnaire: a new and reliable questionnaire for assessing sexual
      dysfunction in Asians with diabetes.
AB  - AIM: The aim of this study is to construct a new tool for the assessment of
      sexual dysfunction among men with diabetes that is valid and reliable across
      different ethnicities, languages and socio-economic backgrounds in South East
      Asia. METHODS: Focus group interviews were conducted to determine the construct
      of the questionnaire. Content and face validity were assessed by a panel of
      experts. A pilot study was conducted to validate the Sexual Dysfunction in Asian
      Men with Diabetes (SAD-MEN) questionnaire in English and Malay. The International
      Index of Erectile Function-5 (IIEF-5) was used for comparison. Construct validity
      was assessed using exploratory factor analysis, reliability was determined using
      Cronbach's alpha (> 0.700), and test-retest reliability using Spearman's rank
      correlation coefficient. RESULTS: The SAD-MEN questionnaire yielded moderate face
      and content validity, with high reliability as shown by Cronbach's alpha values
      of 0.949 for sexual performance and 0.775 for sexual desire for the English
      version. The Malay language questionnaire had a Cronbach's alpha value of 0.945
      for sexual performance and 0.750 for sexual desire. Test-retest reliability using
      Spearman's test gave correlation coefficients of r = 0.853, P = 0.000 for the
      English language questionnaire and r = 0.908, P = 0.000 for the Malay language
      questionnaire. CONCLUSION: The SAD-MEN questionnaire is a valid and reliable tool
      by which to assess sexual dysfunction in English- and Malay-speaking Malaysian
      and South East Asian men with diabetes.

PMID- 26202698
TI  - Transperitoneal robotic resection of benign primary retroperitoneal tumors: can
      it be widely used?
AB  - BACKGROUND: This article was aimed to show the safety, flexibility and other
      advantages of transperitoneal robot-assisted resection of benign primary
      retroperitoneal tumors. METHODS: Ten patients underwent robotic surgeries, and 31
      underwent laparotomy surgeries from 2012 to 2014. The perioperative data,
      including tumor size, operation time, and other parameters were analyzed.
      RESULTS: The tumor sizes of the two groups were not different (robotic group vs
      laparotomy group: 5.47 vs 5.32 cm, respectively; P = 0.777). The differences in
      the blood loss (robotic group vs laparotomy group: 80.00 vs. 146.08 mL,
      respectively; P = 0.021), time of oral intake (robotic group vs laparotomy group:
      2.12 vs. 3.42 d, respectively; P = 0.045) and post-operation hospital stay
      (robotic group vs laparotomy group: 5.40 vs. 8.77 d, respectively; P = 0.004)
      were statistically significant and lower in the robotic group. CONCLUSION: Robot
      assisted resection of benign retroperitoneal tumors is flexible and safe and
      provides better protection when complex lesions are removed. Copyright (c) 2015
      John Wiley & Sons, Ltd.

PMID- 26202697
TI  - MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid pathology and
      cognitive decline in a transgenic mouse model of Alzheimer's disease.
AB  - Membrane-type 5-matrix metalloproteinase (MT5-MMP) is a proteinase mainly
      expressed in the nervous system with emerging roles in brain pathophysiology. The
      implication of MT5-MMP in Alzheimer's disease (AD), notably its interplay with
      the amyloidogenic process, remains elusive. Accordingly, we crossed the
      genetically engineered 5xFAD mouse model of AD with MT5-MMP-deficient mice and
      examined the impact of MT5-MMP deficiency in bigenic 5xFAD/MT5-MMP(-/-) mice. At
      early stages (4 months) of the pathology, the levels of amyloid beta peptide
      (Abeta) and its amyloid precursor protein (APP) C-terminal fragment C99 were
      largely reduced in the cortex and hippocampus of 5xFAD/MT5-MMP(-/-), compared to
      5xFAD mice. Reduced amyloidosis in bigenic mice was concomitant with decreased
      glial reactivity and interleukin-1beta (IL-1beta) levels, and the preservation of
      long-term potentiation (LTP) and spatial learning, without changes in the
      activity of alpha-, beta- and gamma-secretases. The positive impact of MT5-MMP
      deficiency was still noticeable at 16 months of age, as illustrated by reduced
      amyloid burden and gliosis, and a better preservation of the cortical neuronal
      network and synaptophysin levels in bigenic mice. MT5-MMP expressed in HEKswe
      cells colocalized and co-immunoprecipitated with APP and significantly increased
      the levels of Abeta and C99. MT5-MMP also promoted the release of a soluble APP
      fragment of 95 kDa (sAPP95) in HEKswe cells. sAPP95 levels were significantly
      reduced in brain homogenates of 5xFAD/MT5-MMP(-/-) mice, supporting altogether
      the idea that MT5-MMP influences APP processing. MT5-MMP emerges as a new pro
      amyloidogenic regulator of APP metabolism, whose deficiency alleviates amyloid
      pathology, neuroinflammation and cognitive decline.

PMID- 26202702
TI  - Newly learned word forms are abstract and integrated immediately after
      acquisition.
AB  - A hotly debated question in word learning concerns the conditions under which
      newly learned words compete or interfere with familiar words during spoken word
      recognition. This has recently been described as a key marker of the integration
      of a new word into the lexicon and was thought to require consolidation Dumay &
      Gaskell, (Psychological Science, 18, 35-39, 2007; Gaskell & Dumay, Cognition, 89,
      105-132, 2003). Recently, however, Kapnoula, Packard, Gupta, and McMurray,
      (Cognition, 134, 85-99, 2015) showed that interference can be observed
      immediately after a word is first learned, implying very rapid integration of new
      words into the lexicon. It is an open question whether these kinds of effects
      derive from episodic traces of novel words or from more abstract and lexicalized
      representations. Here we addressed this question by testing inhibition for newly
      learned words using training and test stimuli presented in different talker
      voices. During training, participants were exposed to a set of nonwords spoken by
      a female speaker. Immediately after training, we assessed the ability of the
      novel word forms to inhibit familiar words, using a variant of the visual world
      paradigm. Crucially, the test items were produced by a male speaker. An analysis
      of fixations showed that even with a change in voice, newly learned words
      interfered with the recognition of similar known words. These findings show that
      lexical competition effects from newly learned words spread across different
      talker voices, which suggests that newly learned words can be sufficiently
      lexicalized, and abstract with respect to talker voice, without consolidation.

PMID- 26202703
TI  - Similarity effects in visual working memory.
AB  - Perceptual similarity is an important property of multiple stimuli. Its
      computation supports a wide range of cognitive functions, including reasoning,
      categorization, and memory recognition. It is important, therefore, to determine
      why previous research has found conflicting effects of inter-item similarity on
      visual working memory. Studies reporting a similarity advantage have used simple
      stimuli whose similarity varied along a featural continuum. Studies reporting a
      similarity disadvantage have used complex stimuli from either a single or
      multiple categories. To elucidate stimulus conditions for similarity effects in
      visual working memory, we tested memory for complex stimuli (faces) whose
      similarity varied along a morph continuum. Participants encoded 3 morphs
      generated from a single face identity in the similar condition, or 3 morphs
      generated from different face identities in the dissimilar condition. After a
      brief delay, a test face appeared at one of the encoding locations for
      participants to make a same/different judgment. Two experiments showed that
      similarity enhanced memory accuracy without changing the response criterion.
      These findings support previous computational models that incorporate featural
      variance as a component of working memory load. They delineate limitations of
      models that emphasize cortical resources or response decisions.

PMID- 26202708
TI  - New therapies, large databases, and Vale Jack P. Whisnant.

PMID- 26202709
TI  - Heart rate variability and baroreceptor sensitivity in acute stroke: a systematic
      review.
AB  - BACKGROUND: Autonomic nervous system dysfunction is common after acute stroke and
      is associated with elevated risk of cardiac arrhythmia and mortality. Heart rate
      variability and baroreceptor sensitivity have been investigated as parameters of
      autonomic nervous system dysfunction for the prediction of stroke outcome.
      SUMMARY: We performed a systematic literature review on heart rate variability
      and baroreceptor sensitivity as parameters for autonomic nervous function in
      acute stroke. Twenty-two studies were included. Associations between heart rate
      variability or baroreceptor sensitivity and stroke severity, early and late
      complications, dependency and mortality were reported. However, interpretability
      of most studies and extrapolation to general stroke population are limited due to
      many confounding factors such as varying methodology, small sample sizes,
      survival selection, and exclusion of patients with frequently occurring
      comorbidities in stroke. Key issues, such as the effect of thrombolytic therapy
      on autonomic function, autonomic nervous system dysfunction in the hyperacute
      phase of stroke, and correlation with the risk of recurrent stroke have not been
      investigated. Also, nonlinear techniques have remained largely unexplored in this
      domain, in spite of their advantage to provide more solid evaluation in the
      occurrence of arrhythmia. KEY MESSAGES: Cardiac autonomic dysfunction,
      represented by reduced heart rate variability or impaired baroreceptor
      sensitivity, is associated with stroke severity, early and late complications,
      dependency, and mortality. Large-scale prospective studies applying
      internationally accepted standards of measures for analysis of heart rate
      variability and baroreceptor sensitivity are needed in patients with acute
      stroke.

PMID- 26202710
TI  - Pseudobulbar palsy due to bilateral injuries of corticobulbar tracts in a stroke
      patient.

PMID- 26202711
TI  - Acid-suppressive medication use in acute stroke patients: is it time to change
      practice?

PMID- 26202712
TI  - Is intimal hyperplasia associated with cranial arterial stenosis in cannabis
      associated cerebral infarction?

PMID- 26202713
TI  - National Institutes of Health Stroke Scale for prediction of proximal vessel
      occlusion in anterior circulation stroke.

PMID- 26202715
TI  - Peri-infarct reorganization of an injured corticoreticulospinal tract in a
      patient with cerebral infarct.

PMID- 26202714
TI  - Acute isolated trochlear nerve palsy in a patient with cavernous carotid aneurysm
      and visit-to-visit variability in systolic blood pressure.

PMID- 26202716
TI  - Endovascular treatment for acute ischemic stroke: experience in South Australia.

PMID- 26202718
TI  - Ischemic stroke on optimal anticoagulation with novel-oral anticoagulants
      compared with warfarin.

PMID- 26202717
TI  - Development of collateral veins as a favorable prognostic factor for complete
      recovery in cerebral venous thrombosis due to Tribulus terrestris.

PMID- 26202719
TI  - Recurrences in untreated patients with isolated cerebral venous thrombosis.

PMID- 26202720
TI  - Stroke incidence: sensitivity of hospital data coding of acute stroke.

PMID- 26202721
TI  - Foot dermatitis caused by didecyldimethylammonium chloride in a shoe refresher
      spray.

PMID- 26202723
TI  - Review article: the pathophysiology and medical management of diverticulosis and
      diverticular disease of the colon.
AB  - BACKGROUND: The incidence of diverticulosis and diverticular disease of the
      colon, including diverticulitis, is increasing worldwide, and becoming a
      significant burden on national health systems. Treatment of patients with
      diverticulosis and DD is generally based on high-fibre diet and antibiotics,
      respectively. However, new pathophysiological knowledge suggests that further
      treatment may be useful. AIM: To review the current treatment of diverticulosis
      and diverticular disease. METHODS: A search of PubMed and Medline databases was
      performed to identify articles relevant to the management of diverticulosis and
      diverticular disease. Major international conferences were also reviewed.
      RESULTS: Two randomised controlled trials (RCT) found the role of antibiotics in
      managing acute diverticulitis to be questionable, particularly in patients with
      no complicating comorbidities. One RCT found mesalazine to be effective in
      preventing acute diverticulitis in patients with symptomatic uncomplicated
      diverticular disease. The role of rifaximin or mesalazine in preventing
      diverticulitis recurrence, based on the results of 1 and 4 RCTs, respectively,
      remains unclear. RCTs found rifaximin and mesalazine to be effective in treating
      symptomatic uncomplicated diverticular disease. The use of probiotics in
      diverticular disease and in preventing acute diverticulitis occurrence/recurrence
      appears promising but unconclusive. Finally, the role of fibre in treating
      diverticulosis remains unclear. CONCLUSIONS: Available evidence suggests that
      antibiotics have a role only in the treatment of complicated diverticulitis. It
      appears to be some evidence for a role for rifaximin and mesalazine in treating
      symptomatic uncomplicated diverticular disease. Finally, there is not currently
      adequate evidence to recommend any medical treatment for the prevention of
      diverticulitis recurrence.

PMID- 26202724
TI  - Infundibulotomy and endoscopic retrograde cholangiopancreatography in situs
      inversus totalis combined with choledochocele.

PMID- 26202722
TI  - Childbirth and symptoms of postpartum depression and anxiety: a prospective birth
      cohort study.
AB  - We investigated associations between aspects of childbirth and elevated
      postpartum symptoms of depression and anxiety. We employed secondary analysis of
      perinatal data (N = 4657-4946) from the Avon Longitudinal Study of Parents and
      Children (ALSPAC) birth cohort. Multivariable logistic regression models
      (adjusted for covariates) examined predictors of elevated symptoms of postpartum
      depression and anxiety. Predictors included the following: type of delivery
      (normal physiological vs. interventive non-physiological), immediate postpartum
      complications, and maternal perception of the recent birth experience. The
      Edinburgh Postnatal Depression Scale assessed elevated symptoms of depression
      (score >= 13), and the Crown-Crisp Experiential Index assessed elevated symptoms
      of anxiety (score >= 9) at 2 and 8 months after delivery. A more negative
      perception of the recent birth experience was associated with elevated symptoms
      of anxiety at 2 months [odds ratio (OR) 1.52, 95 % confidence interval (CI) 1.25
      1.85] and 8 months (OR 1.30, 95 % CI 1.06-1.60) postpartum but was not associated
      with elevated symptoms of depression at either time point. Type of delivery
      (physiological vs. non-physiological) and immediate postpartum complications were
      not associated with elevated symptoms of depression or anxiety. Our findings
      suggest that improving women's childbirth experience may decrease the likelihood
      of postpartum anxiety, but not postpartum depression.

PMID- 26202726
TI  - Perceived influences on post-diagnostic dietary change among a group of men with
      prostate cancer.
AB  - A cancer diagnosis is often associated with loss of agency and control that can
      adversely affect well-being. Patients may try to regain control through dietary
      change aimed at preventing progression and/or recurrence. Evidence for the
      effectiveness of post-diagnostic dietary change in prostate cancer is not
      conclusive, which can cause uncertainty among patients and health professionals.
      This qualitative study explored how eight men in the U.K., who had been diagnosed
      with prostate cancer in the previous 5 years, accounted for any post-diagnostic
      changes they made to their diet. Data were generated through semi-structured
      telephone interviews and were subjected to thematic analysis. This yielded two
      themes concerning the perceived nature and importance of dietary change and the
      perceived determinants of dietary change. The latter focused on internal
      dimensions such as agency and external dimensions such as the perceived role of
      relationships with health professionals, the availability of credible dietary
      information and family influences. The study points to the importance of the
      family context in enabling the men to implement dietary change. It is suggested
      that, even if health professionals can only offer qualified, general advice about
      diet, this may provide men with a focus for action and a means of regaining
      control.

PMID- 26202725
TI  - Analysing calcium signalling of cells under high shear flows using discontinuous
      dielectrophoresis.
AB  - Immobilisation of cells is an important feature of many cellular assays, as it
      enables the physical/chemical stimulation of cells; whilst, monitoring cellular
      processes using microscopic techniques. Current approaches for immobilising
      cells, however, are hampered by time-consuming processes, the need for specific
      antibodies or coatings, and adverse effects on cell integrity. Here, we present a
      dielectrophoresis-based approach for the robust immobilisation of cells, and
      analysis of their responses under high shear flows. This approach is quick and
      label-free, and more importantly, minimises the adverse effects of electric field
      on the cell integrity, by activating the field for a short duration of 120 s,
      just long enough to immobilise the cells, after which cell culture media (such as
      HEPES) is flushed through the platform. In optimal conditions, at least 90% of
      the cells remained stably immobilised, when exposed to a shear stress of 63
      dyn/cm(2). This approach was used to examine the shear-induced calcium signalling
      of HEK-293 cells expressing a mechanosensitive ion channel, transient receptor
      potential vaniloid type 4 (TRPV4), when exposed to the full physiological range
      of shear stress. 

PMID- 26202727
TI  - Position-specific prediction of methylation sites from sequence conservation
      based on information theory.
AB  - Protein methylation plays vital roles in many biological processes and has been
      implicated in various human diseases. To fully understand the mechanisms
      underlying methylation for use in drug design and work in methylation-related
      diseases, an initial but crucial step is to identify methylation sites. The use
      of high-throughput bioinformatics methods has become imperative to predict
      methylation sites. In this study, we developed a novel method that is based only
      on sequence conservation to predict protein methylation sites. Conservation
      difference profiles between methylated and non-methylated peptides were
      constructed by the information entropy (IE) in a wider neighbor interval around
      the methylation sites that fully incorporated all of the environmental
      information. Then, the distinctive neighbor residues were identified by the
      importance scores of information gain (IG). The most representative model was
      constructed by support vector machine (SVM) for Arginine and Lysine methylation,
      respectively. This model yielded a promising result on both the benchmark dataset
      and independent test set. The model was used to screen the entire human proteome,
      and many unknown substrates were identified. These results indicate that our
      method can serve as a useful supplement to elucidate the mechanism of protein
      methylation and facilitate hypothesis-driven experimental design and validation. 

PMID- 26202728
TI  - Enhanced poly(gamma-glutamic acid) production by H2 O2 -induced reactive oxygen
      species in the fermentation of Bacillus subtilis NX-2.
AB  - Effects of reactive oxygen species (ROS) on cell growth and poly(gamma-glutamic
      acid) (gamma-PGA) synthesis were studied by adding hydrogen peroxide to a medium
      of Bacillus subtilis NX-2. After optimizing the addition concentration and time
      of H2 O2 , a maximum concentration of 33.9 g/L gamma-PGA was obtained by adding
      100 uM H2 O2 to the medium after 24 H. This concentration was 20.6% higher than
      that of the control. The addition of diphenyleneiodonium chloride (ROS inhibitor)
      can interdict the effect of H2 O2 -induced ROS. Transcriptional levels of the
      cofactors and relevant genes were also determined under ROS stress to illustrate
      the possible metabolic mechanism contributing to the improve gamma-PGA
      production. The transcriptional levels of genes belonging to the tricarboxylic
      acid cycle and electron transfer chain system were significantly increased by
      ROS, which decreased the NADH/NAD+ ratio and increased the ATP levels, thereby
      providing more reducing power and energy for gamma-PGA biosynthesis. The enhanced
      gamma-PGA synthetic genes also directly promoted the formation of gamma-PGA. This
      study was the first to use the ROS control strategy for gamma-PGA fermentation
      and provided valuable information on the possible mechanism by which ROS
      regulated gamma-PGA biosynthesis in B. subtilis NX-2.

PMID- 26202729
TI  - Hollow octahedral and cuboctahedral nanocrystals of ternary Pt-Ni-Au alloys.
AB  - Hollow particles of Pt-Ni-Au alloys have been prepared through a two-step
      reaction with the synthesis of NiPt octahedral and cuboctahedral templates
      followed by a galvanic replacement reaction by Au(iii). Metal etching presents an
      efficient method to yield hollow particles and investigate the Au diffusion in
      the metallic Pt-Ni framework through macroscopic (X-ray diffraction and SQUID
      magnetic measurement) and microscopic (HRTEM and STEM) measurements. The hollow
      particles retain the shape of the original nanocrystals. The nucleation of Au is
      found to be induced preferentially on the tip of the polyhedral nanocrystals
      while the etching of Ni starts from the facets leaving hollow octahedral
      particles consisting of 2 nm thick edges. In the presence of oleylamine, the Au
      tip grows and yields a heterogeneous dimer hollow-NiPt/Au. Without oleylamine,
      the Au nucleation is followed by Au diffusion in the Ni/Pt framework to yield a
      hollow single crystal Pt-Ni-Au alloy. The Pt-Ni-Au alloyed particles display a
      superparamagnetic behavior at room temperature. 

PMID- 26202730
TI  - Van der Waals Epitaxial Growth of Two-Dimensional Single-Crystalline GaSe Domains
      on Graphene.
AB  - Two-dimensional (2D) van der Waals (vdW) heterostructures are a family of
      artificially structured materials that promise tunable optoelectronic properties
      for devices with enhanced functionalities. Compared to transferring, direct
      epitaxy of vdW heterostructures is ideal for clean interlayer interfaces and
      scalable device fabrication. Here we report the synthesis and preferred
      orientations of 2D GaSe atomic layers on graphene (Gr) by vdW epitaxy. GaSe
      crystals are found to nucleate predominantly on random wrinkles or grain
      boundaries of graphene, share a preferred lattice orientation with underlying
      graphene, and grow into large (tens of micrometers) irregularly shaped, single
      crystalline domains. The domains are found to propagate with triangular edges
      that merge into the large single crystals during growth. Electron diffraction
      reveals that approximately 50% of the GaSe domains are oriented with a 10.5 +/-
      0.3 degrees  interlayer rotation with respect to the underlying graphene.
      Theoretical investigations of interlayer energetics reveal that a 10.9 degrees 
      interlayer rotation is the most energetically preferred vdW heterostructure. In
      addition, strong charge transfer in these GaSe/Gr vdW heterostructures is
      predicted, which agrees with the observed enhancement in the Raman E(2)1g band of
      monolayer GaSe and highly quenched photoluminescence compared to GaSe/SiO2.
      Despite the very large lattice mismatch of GaSe/Gr through vdW epitaxy, the
      predominant orientation control and convergent formation of large single-crystal
      flakes demonstrated here is promising for the scalable synthesis of large-area
      vdW heterostructures for the development of new optical and optoelectronic
      devices. 

PMID- 26202731
TI  - Different Perspectives of Clinicians and Patients with Severe Mental Illness on
      Motivation for Treatment.
AB  - : The present study assessed motivation for engaging in treatment as rated by
      clinicians (n = 57) and patients with severe mental illness (SMI, n = 294) using
      measures based on three different motivation theories. Questionnaires were
      derived from self-determination theory, the transtheoretical model and the
      integral model of treatment motivation. It was investigated to which extent
      clinicians of patients with SMI were able to estimate their patient's perspective
      on motivation for engaging in treatment, to which extent they agreed on the
      patient's motivation and which factors were associated with estimation and
      agreement on treatment motivation. It was found that clinicians were poorly to
      moderately capable of estimating their patient's type of motivation and readiness
      for change. Further, agreement on the level of motivation between patients and
      clinicians was moderate. These findings were consistent across diagnostic groups
      (psychotic and personality disorders). A higher quality therapeutic relationship
      was generally associated with higher clinician-rated motivation. The patient's
      ethnicity and socially desirable responding were factors that differentiated
      between scales of different motivation theories. It is concluded that patients
      with SMI and their clinicians have different perceptions on the patient's
      motivation for engaging in psychiatric treatment, regardless of the theoretical
      framework that is used to measure motivation. The findings imply that a
      negotiated approach is needed where both perceptions of clinicians and patients
      on motivation for treatment are considered to ensure effective mental health
      interventions. Copyright (c) 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER
      MESSAGE: Clinicians show poor to moderate capability in estimating how patients
      perceive their motivation for engaging in treatment, especially so when the
      patient's motives revolve around feelings of shame and guilt. Clinicians
      generally give higher motivation ratings for patients where they experience a
      higher quality therapeutic relationships with, whereas-depending on the scale
      that is used to measure motivation-they give lower ratings to patients who
      respond in socially desirable ways and to ethnic minority patients. As patients
      with SMI and their clinicians have different perceptions on the patient's
      motivation for engaging in psychiatric treatment (regardless of the theoretical
      framework that is used to assess motivation), this implies that a negotiated
      approach is needed where both perceptions of clinicians and patients on
      motivation for treatment are considered to ensure effective mental health
      interventions.

PMID- 26202732
TI  - Prenatal air pollutant exposure and occurrence of atopic dermatitis.
AB  - BACKGROUND: Hereditary and environmental factors have been related to the
      occurrence of atopic dermatitis (AD) in early childhood. However, the role of
      prenatal and early postnatal exposure to air pollutants has not been totally
      elucidated. OBJECTIVES: To evaluate the association between prenatal air
      pollutant exposure and occurrence of AD. METHODS: In total 24 200 infant-mother
      pairs were recruited to participate in the Taiwan Birth Cohort Study in 2005
      using multistage stratified sampling. Medical history, including physician
      diagnosed AD, was inquired by questionnaire at the infant's age of 6 months.
      Monthly averages of five criteria air pollutants - NO2 , CO, O3 , SO2 and PM10 -
      were retrieved from 66 air-quality-monitoring stations, and interpolated to all
      administrative districts using the kriging method. Exposure data during each of
      the three gestational trimesters and three months after birth were calculated for
      each study subject, and odds ratios (ORs) of AD occurrence were calculated by
      logistic regression. RESULTS: Among the participants, 16 686 mother-infant pairs
      were qualified for and included in the analysis. Among them, 1206 infants (7.2%)
      had been diagnosed as having AD before the age of 6 months, and the prevalence
      was higher in boys (8.3%) than in girls (6.1%). The occurrence of AD was
      significantly associated with CO exposure during the whole gestational period
      [adjusted OR (aOR) 1.37, 95% confidence interval (CI) 1.06-1.78] and the first
      trimester (aOR 1.51, 95% CI 1.16-1.97). We did not observe any significant
      association among the other air pollutants during either the whole gestational
      period or any period of the three trimesters and 3 months after birth.
      CONCLUSIONS: Our study found a relationship between AD occurrence and gestational
      exposure to CO, where exposure during the first trimester seemed to be the most
      important.

PMID- 26202733
TI  - Polystyrene microspheres enable 10-color compensation for immunophenotyping of
      primary human leukocytes.
AB  - Compensation is a critical process for the unbiased analysis of flow cytometry
      data. Numerous compensation strategies exist, including the use of bead-based
      products. The purpose of this study was to determine whether beads, specifically
      polystyrene microspheres (PSMS) compare to the use of primary leukocytes for
      single color based compensation when conducting polychromatic flow cytometry. To
      do so, we stained individual tubes of both PSMS and leukocytes with panel
      specific antibodies conjugated to fluorochromes corresponding to fluorescent
      channels FL1-FL10. We compared the matrix generated by PSMS to that generated
      using peripheral blood mononuclear cells (PBMC). Ideal for compensation is a
      sample with both a discrete negative population and a bright positive population.
      We demonstrate that PSMS display autofluorescence properties similar to PBMC.
      When comparing PSMS to PBMC for compensation PSMS yielded more evenly distributed
      and discrete negative and positive populations to use for compensation. We
      analyzed three donors' PBMC stained with our 10-color T cell subpopulation panel
      using compensation generated by PSMS vs.PBMC and detected no significant
      differences in the population distribution. Panel specific antibodies bound to
      PSMS represent an invaluable valid tool to generate suitable compensation
      matrices especially when sample material is limited and/or the sample requires
      analysis of dynamically modulated or rare events.

PMID- 26202734
TI  - Overexpression of a novel SbMYB15 from Salicornia brachiata confers salinity and
      dehydration tolerance by reduced oxidative damage and improved photosynthesis in
      transgenic tobacco.
AB  - MAIN CONCLUSION: SbMYB15, R2R3-type MYB was induced by the different stresses,
      and conferred stress tolerance in transgenic tobacco by regulating the expression
      of stress-responsive genes. MYBs are the master regulators of various metabolic
      processes and stress responses in plants. In this study, we functionally
      characterised a R2R3-type SbMYB15 transcription factor (TF) from the extreme
      halophyte Salicornia brachiata. The SbMYB15 acts as a transcriptional activator.
      Transcriptional analysis showed that SbMYB15 transcript was strongly upregulated
      in red shoots and was also induced by different stresses; however, its expression
      remained unchanged with ABA. Overexpression of SbMYB15 in tobacco significantly
      improved salinity and dehydration tolerance. The enhanced tolerance of the
      transgenic plants was defined by the changes in chlorophyll, malondialdehyde
      (MDA), proline, total soluble sugar and total amino acid contents. The transgenic
      plants exhibited a higher membrane stability and reduced electrolyte leakage,
      H2O2 and O 2 (-) content compared to the wild type (WT). With ionic stress,
      transgenics showed a low Na(+) and a high K(+) content. In the transgenic plants,
      the expression of stress-responsive genes such as LEA5, ERD10D, PLC3, LTP1, HSF2,
      ADC, P5CS, SOD and CAT was enhanced in the presence of salinity, dehydration and
      heat. Exposure to gradual salinity and dehydration resulted in an increased
      stomatal conductance, water use efficiency, photosynthesis rate, photochemical
      quenching and reduced transpiration rate. Thus, SbMYB15 served as an important
      mediator of stress responses regulating different stress signalling pathways,
      leading to enhanced stress tolerance.

PMID- 26202735
TI  - Homologous sense and antisense expression of a gene in Dunaliella tertiolecta.
AB  - MAIN CONCLUSION: Dunaliella transformation using antisense and sense technology
      developed in this study will provide powerful tools for functional analysis and
      pathway-specific metabolic engineering in Dunaliella for industrial applications.
      Our aim was to investigate the potential of antisense expression and
      overexpression of a specific gene, the carotenoid biosynthesis-related (CBR)
      gene, in the microalgae Dunaliella. DNA amplified from sense and antisense vector
      constructs was used to transform Dunaliella tertiolecta. The Gateway vector for
      plant transformation was used to make an expression cassette, and the essential
      region for Dunaliella transformation was amplified by PCR and used for
      transformation. The transformation efficiency using a 3.2 kb PCR product was 130
      transformants/MUg DNA for both sense and antisense transformations. Among 200
      BASTA-resistant colonies from the sense transformation and antisense
      transformation, separately, nine positive transformants for sense expression and
      five positive transformants for the antisense expression were obtained by genomic
      DNA PCR. The insertion was also verified by genomic Southern analysis. Among five
      positive sense transformants, one transformant was tested and verified for the
      overexpression of CBR-GFP fusion protein by Western blot analysis. One of the
      five antisense transformants showed almost complete inhibition of gene expression
      under light stress conditions (400 MUmol photons m(-2) s(-1)) as determined by
      quantitative RT-PCR and Western blot analysis. Although there was no difference
      in the growth patterns or photosynthetic parameters between the wild type
      (including the vector control) and transformants, the zeaxanthin content of the
      antisense CBR mutant was lowered under light stress conditions. Thus, we show
      that the sense and antisense RNA technology can be easily and strategically used
      for the functional analysis of interesting gene in D. tertiolecta.

PMID- 26202736
TI  - Exploring the diversity in Citrus fruit colouration to decipher the relationship
      between plastid ultrastructure and carotenoid composition.
AB  - MAIN CONCLUSION: Differentiation of new and characteristic plastid
      ultrastructures during ripening of citrus fruits in both peel and pulp appears to
      be strongly correlated with the content and complement of carotenoids. Most of
      the species of the Citrus genus display a wide range in fruit colouration due to
      differences in carotenoids; however, how this diversity is related and may
      contribute to plastid differentiation and ultrastructure is currently unknown. To
      that end, carotenoid profile and plastid ultrastructure were compared in peel and
      pulp of three sweet oranges: the ordinary orange-coloured Navel, rich in
      beta,beta-xanthophylls, the yellow Pinalate mutant with an elevated content of
      colourless carotenes and reduced beta,beta-xanthophylls, and the red-fleshed Cara
      Cara with high concentration of colourless carotenes and lycopene in the pulp;
      and two grapefruits: the white Marsh, with low carotenoid content, and the red
      Star Ruby, accumulating upstream carotenes and lycopene. The most remarkable
      differences in plastid ultrastructure among varieties were detected in the pulp
      at full colour, coinciding with major differences in carotenoid composition.
      Accumulation of lycopene in Cara Cara and Star Ruby pulp was associated with the
      presence of needle-like crystals in the plastids, while high content of upstream
      carotenes in Pinalate pulp was related to the development of a novel plastid type
      with numerous even and round vesicles. The presence of plastoglobuli was linked
      to phytoene and xanthophyll accumulation, suggesting these structures as the main
      sites for the accumulation of these pigments. Peel chromoplasts were richer in
      membranes compared to pulp chromoplasts, reflecting their different biogenesis.
      In summary, differences in carotenoid composition and accumulation of unusual
      carotenoids are mirrored by the development of diverse and novel chromoplast
      types, revealing the plasticity of these organelles to rearrange carotenoids
      inside different structures to allow massive accumulation and thus contributing
      to the chemical stability of the carotenoids.

PMID- 26202737
TI  - Glutamine synthetase activity in leaves of Zea mays L. as influenced by magnesium
      status.
AB  - MAIN CONCLUSION: The total capacity of the GS-mediated ligation of free ammonium
      and glutamate to form glutamine in the leaves of maize plants is not impaired
      upon severe magnesium starvation. Magnesium deficiency does not obligatorily lead
      to the decreased total protein concentrations in the leaves. Magnesium (Mg) is an
      integral component of the enzyme glutamine synthetase (GS), having both a
      structural and a catalytic role. Moreover, Mg is relevant for the post
      translational regulation of the GS. Glutamine synthetase is one of the key
      enzymes in nitrogen assimilation, ligating-free ammonium (NH4 (+)) to glutamate
      to form glutamine and it is therefore crucial for plant growth and productivity.
      This study was conducted in order to test whether a severe Mg-deficiency impairs
      the total capacity of the GS-catalyzed synthesis of glutamine in maize leaves.
      Maize was grown hydroponically and the GS activity was analyzed dependent on
      different leaf developmental stages. Glutamine synthetase activity in vitro
      assays in combination with immune-dot blot analysis revealed that both the total
      activity and the abundance of glutamine synthetase was not impaired in the leaves
      of maize plants upon 54 days of severe Mg starvation. Additionally, it was shown
      that Mg deficiency does not obligatorily lead to decreased total protein
      concentrations in the leaves, as assayed by Bradford protein quantification.
      Moreover, Mg resupply to the roots or the leaves of Mg-deficient plants reversed
      the Mg-deficiency-induced accumulation of free amino acids in older leaves, which
      indicates impaired phloem loading. The results of our study reveal that the total
      GS-mediated primary or secondary assimilation of free NH4 (+) is not a limiting
      enzymatic reaction under Mg deficiency and thus cannot be accountable for the
      observed restriction of plant growth and productivity in Mg-deficient maize.

PMID- 26202738
TI  - Diagnosis and Treatment Options of Spinal Metastases.
AB  - Cancer patients with spinal metastases are a diagnostic and treatment challenge
      for the clinician. This challenge must be addressed through a multidisciplinary,
      multimodal, and individualized management. The presence of tumor cells in bone
      metastases results in homeostatic disruption between bone formation and
      remodeling. Bone destruction is a late event in the formation of lytic bone
      metastasis, starting when tumor cells proliferate; this in turn activates
      osteoclasts, seen as trabecular destruction in imaging studies. There may be
      excessive bone destruction and increased bone formation, which produce blastic
      lesions. Bone scintigraphy is currently the most widely used diagnostic method
      and is considered as the reference test for the diagnosis of spinal bone
      metastasis. However, we believe that in the near future positron emission
      tomography associated to computed tomography with 18F-NaF, or magnetic resonance
      using diffusion-weighted whole-body imaging with background body signal
      suppression, will replace bone scintigraphy due to their improved diagnostic
      accuracy. These new diagnostic tools will help prevent bone metastasis
      complications such as: intractable pain; spinal cord or cauda equina compression;
      hypercalcemia; pathological fractures; and spinal instability. With regards to
      the treatment, it can be uni- or multimodal, depending on the type and number of
      bone metastases. Among the types of treatment available for bone metastasis are
      chemotherapy, radiotherapy, and invasive procedures. The prognosis of patient
      survival depends on the histopathology of the primary tumor, the presence of bone
      metastasis, and the presence of neurological deficits. 

PMID- 26202739
TI  - Technological Evolution in the Development of Therapeutic Antibodies.
AB  - Immunotherapy is defined as the use of the immune system or components of it,
      such as key immune molecules, to fight diseases or invading infectious agents.
      Modern biotechnology provides industrial versions of immune molecules (components
      of the immune system) naturally produced by the human body. Immune molecules such
      as monoclonal antibodies are used as therapeutics in several disease conditions.
      In recent years a new group of antibody based molecules has been developed to
      replace monoclonal antibodies, given their ability to overcome some of the
      limitations of the latter. The first clinical trials with these new molecules
      have been very encouraging and the promise is that they will be released to the
      market very soon. This in turn has stimulated more research on new versions of
      antibody based therapeutics by biotechnological companies supported by the
      pharmaceutical industry and in many cases in collaboration with academic
      institutions. 

PMID- 26202740
TI  - Risk Factors Associated with Nosocomial Peritonitis in Children on Peritoneal
      Dialysis.
AB  - BACKGROUND: Peritoneal dialysis is the most frequent dialysis method in children,
      and peritonitis is a frequent complication. The responsible organisms differ
      between nosocomial and community acquired peritonitis, they cause longer
      hospitalization time, and can lead to dialysis failure. OBJECTIVE: The aim of the
      study was to describe the risk factors associated with nosocomial peritonitis in
      children with end-stage renal disease undergoing dialysis treatment. METHODS: A
      nested case-control study was conducted in an academic medical center. SUBJECTS:
      The basic cohort included all pediatric patients with end-stage renal disease
      undergoing continuous ambulatory peritoneal dialysis therapy and who were
      hospitalized for non-infectious causes during the study period, January 2008 to
      December 2009. Cases were subjects who developed nosocomial peritonitis during
      hospitalization, and controls were children free of nosocomial peritonitis. The
      final groups consisted of 10 cases and 35 controls. RESULTS: There were 11
      episodes of nosocomial peritonitis in 10 subjects (incidence rate, 6.6 cases per
      year of hospitalization). By multiple logistic regression analysis, the presence
      of congenital abnormalities of the kidney and urinary tract was the only risk
      factor significantly associated with nosocomial peritonitis (OR: 11.54; 95% CI:
      1.86-71.59). CONCLUSION: Congenital abnormality of the kidney and urinary tract
      was a significant risk factor for nosocomial peritonitis in pediatric patients
      with end-stage renal disease undergoing peritoneal dialysis.

PMID- 26202741
TI  - Decrease in the Prevalence of Pancreatitis Associated with Primary
      Hyperparathyroidism: Experience at a Tertiary Referral Center.
AB  - BACKGROUND: Hypercalcemia is a rare but well recognized cause of acute and
      chronic pancreatitis. Hypercalcemia-related pancreatitis is mainly caused by
      primary hyperparathyroidism. The prevalence of pancreatitis in
      hyperparathyroidism varies worldwide and additional disease-modifying factors may
      play a role in its development. In 1988 the prevalence of pancreatitis secondary
      to primary hyperparathyroidism at the Instituto Nacional de Ciencias Medicas y
      Nutricion Salvador Zubiran (INCMNSZ), a referral center in Mexico City, was 12.1%
      (95% CI: 6.7-21). OBJECTIVE: To describe the current prevalence of pancreatitis
      secondary to primary hyperparathyroidism at the INCMNSZ. METHODS: We reviewed 385
      cases of primary hyperparathyroidism seen at the hospital between 1987 and 2012.
      RESULTS: 26 cases with acute or chronic pancreatitis associated with primary
      hyperparathyroidism were documented, with a prevalence of 6.7% (95% CI: 4.6-9.7),
      which was lower than the 12.1% previously reported. In the present study, 20% had
      a history of alcohol consumption, 10% of gallstones, and 20% of ureteral calculi,
      compared with the previously reported 32.0, 34.6, and 40.0%, respectively. The
      average calcium levels were 13.1 and 13.8 mg/dl in the previous and current
      series, respectively. CONCLUSIONS: We found a decrease in the prevalence of
      pancreatitis associated with primary hyperparathyroidism from 12.1% (95% CI: 6.7
      21) to 6.7% (95% CI: 4.6-9.7).

PMID- 26202742
TI  - Assessment of the Usefulness of the Quantitative Methods for the Response
      Evaluation of Solid Tumors: Analysis Using Four Cancer Types.
AB  - BACKGROUND: The evidence provided by medical imaging techniques for the staging
      and follow-up is relevant in oncology. OBJECTIVES: The aims were (i) to compare
      the monitoring methods, (ii) to analyze the response variability between
      different tumors, and (iii) to decipher a general response curve that is
      independent of tumor type and drug treatment. METHODS: We analyzed the response
      variability in four cancer types, looking for a general response curve
      independent of the tumor type and drug treatment. We compared the response of
      different types of lesions within each cancer type via an intra-class correlation
      coefficient, determining the minimum number of lesions suitable for monitoring.
      RESULTS: The tested metrics allowed an objective evaluation of the response of
      solid tumors. The response was homogeneous between different cancer types. The
      intra-class correlation was high, allowing the monitoring of the response with a
      low number of lesions (2-4). The currently used metrics misrepresent the changes
      in the lesion volumes. Indeed, we observed non-linear overestimations of the
      RECIST and WHO values, which were more pronounced for the intermediate values.
      Additionally, the inclusion of lymphadenopathy among the target lesions produced
      a distortion in the evaluation of the response. CONCLUSION: The quantitative
      counts allowed an objective evaluation of the response of the solid tumors to
      therapy, showing that the response was homogeneous but variable between different
      types of tumors. Although the currently used metrics lead to misrepresentations
      of the changes in the lesion volume, they allowed setting a response pattern for
      tracking these lesions.

PMID- 26202743
TI  - Distal Renal Tubular Acidosis Screening by Urinary Acidification Testing in
      Mexican Children.
AB  - BACKGROUND: Primary distal renal tubular acidosis is a clinical disorder
      characterized by hyperchloremic metabolic acidosis, hypercalciuria,
      hypocitraturia, urinary acidification impairment, hypokalemia, metabolic bone
      disease, and nephrocalcinosis. Urinary acidification ability may be evaluated by
      an acidification test or maximum urinary pCO2 assessment with alkaline urine. The
      maximum urinary pCO2 test using acetazolamide and sodium bicarbonate is an easy
      test to confirm the lack of urine acidification in distal renal tubular acidosis
      in children. OBJECTIVE: To determine the urinary acidification ability using the
      maximum urinary pCO2 assessment in a group of children with a distal renal
      tubular acidosis diagnosis. MATERIAL AND METHODS: Thirty children were evaluated
      (13 males and 17 females); 23 children had been diagnosed with distal renal
      tubular acidosis by other physicians and were under alkali treatment with
      potassium and sodium citrates (21) and bicarbonate (2), and five children were
      not under alkali treatment. Two children had been diagnosed with primary distal
      renal tubular acidosis by our medical group. The maximum urinary pCO2 was
      determined by the oral intake of acetazolamide and sodium bicarbonate. RESULTS:
      Two cases with primary distal renal tubular acidosis were found, and they had a
      history of dehydration episodes during infancy and showed hyperchloremic
      metabolic acidosis with hypokalemia. They also exhibited urine acidification
      impairment with furosemide and reduced urinary pCO2 (< 60 mmHg), and the urine
      blood pCO2 gradient was reduced in both cases (< 30 mmHg). One of them developed
      bilateral sensorineural deafness, while the other showed severe hypocitraturia.
      One case of proximal or type 2 renal tubular acidosis with hyperaminoaciduria was
      identified. Twenty-eight children displayed normal urinary acidification and did
      not show signs of distal renal tubular acidosis. CONCLUSIONS: The urinary
      acidification test with furosemide and urinary pCO2 assessment are reliable tests
      to identify the renal excretion of hydrogen ions (H+) and allow confirmation of
      the lack of urine acidification in distal renal tubular acidosis.

PMID- 26202744
TI  - Prognostic Value of Dobutamine Stress Echocardiography in Predicting Major
      Cardiac Events in Patients with Metabolic Syndrome.
AB  - BACKGROUND: The metabolic syndrome increases cardiovascular mortality. We report
      the mid-term prognostic value of dobutamine echocardiography for metabolic
      syndrome. PATIENTS AND METHODS: A dobutamine echocardiography protocol was
      performed in patients aged 18 years of age or older who suffered from chest pain
      and who were followed-up for two years. The patients were divided in two groups,
      with and without metabolic syndrome. Statistical analyses were performed using
      ROC curves and survival analysis; the Begg-Greenes method was used to correct for
      verification bias. We included 128 patients, 66 with metabolic syndrome and 62
      without. RESULTS: Forty-one patients with metabolic syndrome and 36 without had
      positive dobutamine echocardiography test results (p = 0.77). Coronary artery
      disease was found in 27 patients with metabolic syndrome and in 29 without
      metabolic syndrome; percutaneous revascularization was required in 24 and 26
      patients, respectively (p = 0.29). Cardiovascular events occurred in 28 patients
      during follow-up (19 in metabolic syndrome vs. 9 in non-metabolic syndrome; p =
      0.17). The odds ratio of major cardiovascular events in the metabolic syndrome
      group was 5.8 (95% CI: 1.74-19.60); in the control group it was 8.6 (95% CI: 2.53
      29.59). CONCLUSION: Dobutamine echocardiography for metabolic syndrome has high
      sensitivity but is not a determining factor for mid-term prognosis.

PMID- 26202745
TI  - Management of adjunctive antithrombotic therapy in STEMI patients treated with
      fibrinolysis undergoing rescue or delayed PCI.
AB  - Although primary percutaneous coronary intervention (PCI) is the recommended
      method of reperfusion in patients presenting with ST-segment elevation myocardial
      infarction (STEMI), fibrinolysis remains a beneficial alternative in patients who
      cannot be reperfused timely with primary PCI, and is still the preferred
      revascularisation strategy in many parts of the world where PCI facilities are
      unavailable. Because fibrinolysis is known to activate platelets and promote
      thrombin activity, concomitant administration of antiplatelet and anticoagulant
      therapies is needed to lower the risk for re-occlusion and to support mechanical
      interventions in patients undergoing rescue or delayed PCI. However, the addition
      of oral antiplatelet and parenteral anticoagulant drugs on top of fibrinolysis
      may come at the price of an increased risk of bleeding. The current availability
      of several antiplatelet and anticoagulant therapies often leads to questions
      about the optimal selection in STEMI patients treated with fibrinolytics. This
      article appraises current evidences for the management of adjunctive antiplatelet
      and anticoagulant therapies in patients with STEMI undergoing fibrinolysis
      followed by rescue or delayed PCI. 

PMID- 26202746
TI  - Colin A. Wraight, 1945-2014.
AB  - Colin Allen Wraight, a central figure in photosynthetic electron transfer
      research since the 1970s, died in Urbana, Illinois, on July 10, 2014. Born in
      London, England, on November 27, 1945, he had only recently retired from his
      position as a Professor in Biochemistry, Biophysics & Quantitative Biology, and
      Plant Biology at the University of Illinois at Urbana-Champaign. Wraight was
      known especially for his pioneering studies on electron and proton transfer in
      the photochemical reaction center, and for his careful quantitation of the
      remarkable quantum efficiency of this device. 

PMID- 26202748
TI  - Interinstrumental method transfer of a capillary electrophoretic separation of
      angiotensin II and five derivatives: Evaluation and update of earlier developed
      guidelines.
AB  - The increased interest in the separation of peptides, proteins, immunoglobulins,
      and polynucleotides, led to an increased demand for appropriate analytical
      methodologies and instrumentation. CE, because of its unique separation mechanism
      and high efficiency, is frequently used in the analysis of those molecules. In
      this study, a CE method for the separation of six angiotensin analogues was
      developed in the first step. In the second step, the method was transferred to a
      CE instrument of another brand, taking into account guidelines defined earlier
      about the interinstrumental transfer of CE methods. Although previously
      successful, the application of these guidelines during this study was not able to
      maintain the baseline separation. Further research on the instrumental
      differences revealed that the electrical resistance on both instruments differed.
      At constant current, the electrical resistance, generated voltage, and separation
      efficiency on the Agilent instrument were lower than on the Beckman instrument.
      Increase of the electrical resistance, by reducing the capillary temperature,
      leads to an increased applied voltage and separation efficiency on the Agilent
      system. The guidelines developed earlier were, therefore, updated with an
      additional step equalizing the electrical resistances, which led to a successful
      interinstrumental analytical method transfer for the separation of six
      angiotensin derivatives.

PMID- 26202747
TI  - Tanshinone I inhibits tumor angiogenesis by reducing Stat3 phosphorylation at
      Tyr705 and hypoxia-induced HIF-1alpha accumulation in both endothelial and tumor
      cells.
AB  - Tanshinone I (Tanshinone-1), a major active principle of Salvia miltiorrhiza
      (Danshen), has been shown to overcome tumor drug resistance and metastasis. Here
      we report that tanshinone-1 inhibits angiogenesis. Tanshinone-1 inhibited
      proliferation, migration and tube formation of vascular endothelial cells, rat
      aortic ring sprouting and the neovascularization of the chick chorioallantoic
      membrane in a concentration-dependent manner. In endothelial cells, tanshinone-1
      almost completely inhibited phosphorylation of Stat3 at Tyr705 regardless of
      hypoxia or normoxia but only slightly decreased the hypoxia-induced HIF-1alpha
      accumulation. In tumor cells, contrastively, tanshinone-1 could not only make
      phosphorylation of Stat3 at Tyr705 disappear but also reduce the hypoxia-induced
      accumulation of HIF-1alpha to its baseline levels at normoxia. Consequently, VEGF
      secretion from tumor cells was reduced, which could potentiate the direct
      inhibition of tanshinone-1 on endothelial cells. Together with its overcoming
      tumor drug resistance and metastasis, our results reveal unique characteristics
      of tanshinone-1 and its improved derivatives as promising angiogenesis
      inhibitors. 

PMID- 26202749
TI  - How public reporting of prescription quality indicators influence prescribing
      practices? A survey of general practitioners.
AB  - RATIONALE, AIMS AND OBJECTIVES: Public reporting of performance data is one of
      the most popular topics in health care field. The aim of this study was to
      investigate the transparency mechanism, that is, how public reporting influenced
      general practitioners' (GPs) prescribing practices. METHOD: GPs who had the
      license to prescribe medicine of all 10 primary care institutions were surveyed.
      Data were collected by an instrument, which exhibited satisfactory reliability
      and validity (Cronbach's alpha > 0.7; average variance extracted > 0.5; composite
      reliability > 0.7). Data analysis was conducted by structural equation model.
      RESULTS: The results showed that GPs' perceived value (GP's overall assessment of
      the worth of the public reporting) and attitude (the psychological reaction to
      public reporting) had a significantly direct effect on behavioural intention (r =
      0.28; r = 0.36), and were affected by information accessibility (r = 0.63; r =
      0.32). Attitude had a significant effect on perceived value(r = 0.45). Perceived
      risk (the perceptions of the possible loss due to public reporting, e.g.
      decreasing their income) did not have a significant relationship with information
      accessibility, attitude and behavioural intention(r = -0.09; r = 0.01; r = 
      0.07). CONCLUSION: The information accessibility, perceived value and attitude
      have strong effects on prescribing practices of GPs, whereas perceived risk did
      not play a role in influencing the prescribing practices. Policymakers need to
      improve the accessibility of prescription quality indicators and pay attention to
      the perceived values and attitudes of GPs. Policymakers also need to strengthen
      the risk education of GPs and attach incentives to transparent regulation.

PMID- 26202750
TI  - Effect of alpha-Heteroatoms on the Formation of Alkene-Derived Monolayers on H
      Si(111): A Combined Experimental and Theoretical Study.
AB  - We investigate herein whether the reactivity and surface coverage of 1-alkenes
      toward hydrogen-terminated Si(111) surfaces [H-Si(111)] can be improved by
      introducing heteroatoms such as oxygen and sulfur at the alpha-position next to
      the alkene functional group. To this end, the reactivity of 1-pentene, 1-pentyne,
      vinyl ethyl ether, and vinyl ethyl sulfide toward H-Si(111) and the surface
      coverage of the resulting monolayers were studied and compared. All modified
      surfaces were characterized by static water contact angle measurements,
      ellipsometry, X-ray photoelectron spectroscopy (XPS), and infrared absorption
      reflection spectroscopy (IRRAS). Quantum chemical calculations were performed to
      calculate the activation barriers and driving forces for monolayer formation at
      the M11-L/6-311G(d,p) level of theory. Both experiments and theory indicate that
      the presence of alpha-heteroatoms next to the alkene function improved both the
      reactivity and surface coverage on H-terminated Si(111) surfaces. 

PMID- 26202752
TI  - Assessment of diastolic function in the management of patients with cirrhosis.

PMID- 26202753
TI  - The burden of extended-spectrum beta-lactamase-producing Enterobacteriaceae in
      patients with cirrhosis.

PMID- 26202754
TI  - Diagnostic role of radiolabelled choline PET or PET/CT in hepatocellular
      carcinoma: a systematic review and meta-analysis.
AB  - The role of fluorine-18-fluorodeoxygluose positron emission tomography/computed
      tomography ((18)F-FDG PET/CT) in hepatocellular carcinoma (HCC) has not been
      firmly established yet and its sensitivity has been reported to be in the range
      of 40-60 %. Because of this relatively low sensitivity alternative tracers have
      been proposed. The aim of our review is to analyse the literature data on the
      diagnostic role of (18)F/(11)C-choline PET/CT in the evaluation of HCC. A
      comprehensive computer literature search of PubMed/MEDLINE, Embase and Scopus
      databases was conducted to find relevant published articles about the role of
      whole-body (18)F-choline or (11)C-choline PET or PET/CT in patients with HCC.
      Furthermore, a meta-analysis about the detection rate of this method in HCC was
      performed. Six articles were included in this systematic review and discussed.
      The meta-analysis of five out of six articles showed a DR of 84 % (95 % CI 79-89
      %). The DR increased when poorly differentiated HCC was excluded from the
      analysis. Radiolabelled choline PET or PET/CT could be a valuable tool in
      detecting HCC and it is better than (18)F-FDG PET/CT, especially in well to
      moderately differentiated lesions; on the other hand, poorly differentiated and
      higher-stage HCC could be better evaluated with (18)F-FDG and dual tracer imaging
      should be considered and could be potentially useful to increase accuracy. 

PMID- 26202751
TI  - Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific
      Association for the Study of the Liver (APASL) 2014.
AB  - The first consensus report of the working party of the Asian Pacific Association
      for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver
      failure (ACLF) was published in 2009. Due to the rapid advancements in the
      knowledge and available information, a consortium of members from countries
      across Asia Pacific, "APASL ACLF Research Consortium (AARC)," was formed in 2012.
      A large cohort of retrospective and prospective data of ACLF patients was
      collated and followed up in this data base. The current ACLF definition was
      reassessed based on the new AARC data base. These initiatives were concluded on a
      2-day meeting in February 2014 at New Delhi and led to the development of the
      final AARC consensus. Only those statements which were based on the evidence and
      were unanimously recommended were accepted. These statements were circulated
      again to all the experts and subsequently presented at the annual conference of
      the APASL at Brisbane, on March 14, 2014. The suggestions from the delegates were
      analyzed by the expert panel, and the modifications in the consensus were made.
      The final consensus and guidelines document was prepared. After detailed
      deliberations and data analysis, the original proposed definition was found to
      withstand the test of time and identify a homogenous group of patients presenting
      with liver failure. Based on the AARC data, liver failure grading, and its impact
      on the "Golden therapeutic Window," extra-hepatic organ failure and development
      of sepsis were analyzed. New management options including the algorithms for the
      management of coagulation disorders, renal replacement therapy, sepsis, variceal
      bleed, antivirals, and criteria for liver transplantation for ACLF patients were
      proposed. The final consensus statements along with the relevant background
      information are presented here. 

PMID- 26202755
TI  - Real-life practice of antiviral therapy and disease patterns of patients with
      chronic hepatitis B: a single-center retrospective observation study.
AB  - PURPOSE: To analyze the spectrum of diseases in patients with chronic hepatitis B
      virus (HBV) infection and their association with patient clinicopathologic
      characteristics and the effect of antiviral therapy on the spectrum of diseases
      in the study cohort. METHODS: We retrospectively reviewed the clinicopathologic
      and virologic records of patients with chronic HBV infection hospitalized at our
      institution during 2011. Demographic data, hepatitis B e antigen (HBeAg) status
      and HBV DNA (log10 IU/ml) were obtained. RESULTS: A total of 1,619 patients were
      included; 272 (17.2 %) patients received antiviral therapy for a mean duration of
      24.5 +/- 18.3 months, and 71.0 % (198/279) patients were compliant with their
      antiviral therapy. HBeAg-positive patients had a markedly higher rate of moderate
      and severe CHB than HBeAg-negative patients (p < 0.001) but a significantly lower
      rate of liver cirrhosis (p < 0.001). The rate of severe and fulminant CHB was
      significantly lower in patients receiving antiviral therapy than in those not
      receiving antiviral therapy. CONCLUSIONS: Patients receiving antiviral therapy
      exhibit a different spectrum of diseases from patients not receiving such
      therapy.

PMID- 26202756
TI  - Hepatitis B virus genotype B and mutations in basal core promoter and pre
      core/core genes associated with acute-on-chronic liver failure: a multicenter
      cross-sectional study in China.
AB  - BACKGROUND AND AIM: In China, acute-on-chronic liver failure (ACLF) is mostly
      caused by hepatitis B virus (HBV). However, the mechanism remains unclear. This
      study aims to investigate the association between both HBV genotype and mutations
      in basal core promoter (BCP) and pre-core/core (pre-C/C) regions with the
      development of HB-ACLF. METHODS: A multicenter cross-sectional study was
      performed in China. Serum samples from 522 patients were analyzed, including 231
      patients with mild-chronic hepatitis B (CHB-M), 84 with severe-chronic hepatitis
      B (CHB-S) and 207 with HB-ACLF. HBV genotype and related mutations in the BCP and
      pre-C/C regions were determined by direct sequencing. RESULTS: A significantly
      higher ratio of HBV genotype B to C was detected in HB-ACLF patients than in CHB
      M or CHB-S patients. The A1762T/G1764A, A1846T and G1896A mutations were
      significantly more common in HB-ACLF patients infected with either genotype B or
      C as compared with CHB-M, whereas the C1913A/G and A2159G mutations were more
      associated with HB-ACLF in genotype C patients. Comparing with CHB-S, the
      A1762T/G1764A mutation in genotype B and the A2159G mutation in genotype C were
      significantly more common in HB-ACLF patients. A multivariate analysis showed
      that factors such as HBV genotype B, age >=40 years and A1762T/G1764A, A1846T and
      G1896A mutations were independently associated with the development of HB-ACLF.
      CONCLUSION: Chronic HBV infection with genotype B, A1762T/G1764A, A1846T and
      G1896A mutations has a higher possibility to develop HB-ACLF. These virological
      factors could serve as possible molecular markers for prediction of the clinical
      outcomes of chronic HBV infection.

PMID- 26202757
TI  - Extended treatment with pegylated interferon alfa/ribavirin in patients with
      genotype 2/3 chronic hepatitis C who do not achieve a rapid virological response:
      final analysis of the randomised N-CORE trial.
AB  - BACKGROUND AND AIMS: The combination of pegylated interferon alfa/ribavirin will
      likely remain the treatment of choice for HCV genotype 2/3 patients in
      financially constrained countries for the foreseeable future. Patients with poor
      on-treatment response may benefit from treatment extension. This study examined
      the effect of 48 versus 24 weeks of peginterferon alfa-2a/ribavirin on the
      sustained virological response (SVR) in patients with HCV genotype 2/3 who did
      not achieve rapid virological response (RVR). METHODS: N-CORE was a multicentre,
      randomised, phase III study. HCV genotype 2/3 patients receiving peginterferon
      alfa-2a/ribavirin without a rapid but with an early virological response were
      randomised at week 24 to stop treatment (Arm A) or continue to 48 weeks (Arm B).
      The primary efficacy endpoint was SVR. RESULTS: Two hundred thirty-five patients
      were enrolled. End of treatment response was similar in both treatment arms.
      SVR24 rates were not significantly greater in the extended treatment arm compared
      with the standard 24-week treatment in either the intention-to-treat or the per
      protocol populations (61 vs. 52 %, p = 0.1934 and 63 vs. 52 %, p = 0.1461,
      respectively). Serious adverse events occurred more frequently in patients
      receiving extended treatment duration (12 %) versus 24-week therapy (4 %).
      CONCLUSIONS: It is unclear whether the extension of peginterferon alfa
      2a/ribavirin treatment may benefit HCV genotype 2/3 patients who do not achieve
      RVR. The study was stopped early because recruitment was slower than anticipated,
      and this may have limited the statistical impact of these findings.

PMID- 26202758
TI  - The natural history of HCV-related cirrhosis and its temporal progression across
      the different clinical stages.
AB  - PURPOSE: The clinical course of hepatitis C virus-related cirrhosis and its
      temporal progression across the different clinical stages has not been completely
      investigated. Our study evaluated the cumulative incidences (CIs) of clinical
      outcomes marking disease progression across the different clinical stages.
      METHODS: At baseline, 660 patients were classified as compensated [absence (294),
      or presence (108) of gastroesophageal varices] or decompensated [ascites (144),
      variceal bleeding alone (45) or in combination with ascites (17) and
      encephalopathy alone or together with bleeding and/or ascites (52)]. Subjects
      were followed for 312 weeks to identify time to a first event marking disease
      progression. RESULTS: Among compensated patients without varices, the 312-week
      CIs for developing varices, ascites, and encephalopathy were 37.4, 13.6 and 3.5
      %, respectively. The 312-week CIs of development of ascites, bleeding and
      encephalopathy were 24, 12.5 and 9.9 % for compensated subjects with varices,
      respectively. Among patients with ascites, the 312-week CIs of bleeding, liver
      related deaths/transplant and encephalopathy were 23.5, 27.8, and 47.3 %,
      respectively. The 312-week CIs of ascites, liver-related deaths/transplant and
      encephalopathy were 22.5, 14.7 and 5.7 % among patients with bleeding; however,
      CIs of liver-related deaths were significantly higher in those with ascites plus
      bleeding (77.6 %). Patients with encephalopathy alone or in combination with
      ascites and/or bleeding displayed the highest rates of deaths (312 weeks, 90 %).
      CONCLUSIONS: Among compensated patients, the presence of varices suggests a more
      accelerated course of the disease. Decompensated patients show the most severe
      clinical course, particularly in those with a combination of two or more clinical
      events.

PMID- 26202759
TI  - Meta-analysis of patients with hepatitis C virus genotype 6: 48 weeks with
      pegylated interferon and ribavirin is superior to 24 weeks.
AB  - BACKGROUND: Hepatitis C virus genotype 6 (HCV-6) is common in patients from
      Southeast Asia and the surrounding regions. Optimal treatment duration for HCV-6
      is unknown given the inconclusive evidence from studies with varying
      methodologies and small sample sizes. METHODS: A literature search for 'genotype
      6' in MEDLINE and EMBASE in October 2013 produced 161 and 251 articles,
      respectively. Additional abstracts were identified from four major international
      GI/liver conferences in 2012/2013. Inclusion criteria were original studies with
      >=10 HCV-6 treatment-naive patients treated with pegylated interferon + ribavirin
      (PEG IFN+RBV). Exclusion criteria were coinfections with HBV, HIV, other HCV
      genotypes, and/or other liver diseases. Primary outcome was pooled sustained
      virologic response (SVR). Heterogeneity was defined by Cochrane Q test (p value
      of 0.10) and I (2) statistic (>=50 %). RESULTS: A total of 13 studies with 641
      patients were included. The pooled SVR estimate was 77 % (CI 70-83 %) (Q value =
      38.4, p value <0.001, I (2) = 68.7 %) overall, 79 % (CI 73-84 %) for the 48-week
      group and 59 % (CI 46-70 %) for 24-week group, respectively. In studies with
      direct comparison of the two groups, SVR was superior in patients treated for 48
      versus 24 weeks, OR 1.9 (CI 1.08-3.2, p = 0.026). In studies with direct
      comparison of patients with rapid virologic response (RVR), there was no
      difference in SVR between 48 versus 24 weeks, OR 1.74 (CI 0.65-4.64, p = 0.27).
      CONCLUSION: Hepatitis C virus genotype 6 patients should be treated for 48 weeks,
      and those who achieve RVR may receive the shorter 24-week treatment duration. The
      high SVR (~80 %) with 48 weeks of PEG IFN+RBV therapy may be a cost-effective
      option for HCV-6 patients from resource-poor regions.

PMID- 26202760
TI  - Assessment of the features of serum apolipoprotein profiles in chronic HCV
      infection: difference between HCV genotypes 1b and 2.
AB  - BACKGROUND: The life cycle of hepatitis C virus (HCV) is tightly associated with
      host lipoprotein metabolic pathways. Apolipoprotein is present on the outer
      surface of lipoprotein particles and plays an important role in lipoprotein
      metabolism. We aimed to elucidate the influence of chronic HCV infection on serum
      apolipoprotein profiles. METHODS: Fasting serum apolipoprotein profiles of 310
      subjects with active or cleared HCV infection were examined. Subsequently, the
      association between chronic HCV infection and serum apolipoprotein levels was
      determined using multiple regression analysis. RESULTS: Active HCV infection was
      associated with high serum levels of apo A-II and low serum levels of apo C-II
      and C-III. HCV infection with both genotype 1b (G1b) and genotype 2 (G2) was
      associated with low serum levels of either apo C-II and C-III, whereas only HCV
      G1b infections caused elevated levels of apo A II and E. Among active HCV
      infections, HCV G1b was associated with an elevation in the serum apo E levels.
      Furthermore, IL28B non-major genotype (rs8099917 TG/GG) was associated with low
      levels of serum apo B and high levels of apoA-II, and advanced fibrosis was
      associated with low levels of apo B and C-II in G1b infection. CONCLUSIONS:
      Active HCV infection is distinctively associated with characteristic serum
      apolipoprotein profiles. The influence on apolipoprotein profiles varies with
      different HCV genotypes. Moreover, the genotype of IL28B and hepatic fibrosis
      affected serum apolipoproteins in G1b infection. Abnormalities in serum
      apolipoproteins may provide a clue to the elucidation of complex interactions
      between active HCV infection and lipid metabolism.

PMID- 26202761
TI  - Favorable adverse event profile of sofosbuvir/ribavirin compared to
      boceprevir/interferon/ribavirin for treatment of hepatitis C.
AB  - BACKGROUND: Triple therapy for the treatment of hepatitis C virus (HCV) with
      first-generation directly acting antiviral agents, the non-structural serine
      protease inhibitors boceprevir (BOC) and telaprevir have resulted in improved
      sustained virologic response (SVR) rates. However, a high incidence of adverse
      events (AEs), high pill burdens and drug interactions remain significant barriers
      to successful completion of therapy. The aim of this study was to evaluate the
      AEs observed with BOC triple therapy in comparison to IFN-free
      sofosbuvir/ribavirin (SOF/RBV) therapy in HCV monoinfected, genotype-1 (GT-1)
      individuals. METHODS: We retrospectively evaluated HCV monoinfected, treatment
      naive or -experienced, GT-1 individuals treated with either BOC/IFN/RBV at the
      Veterans Affairs Medical Center, Baltimore (n = 97) or SOF/RBV in the NIAID SPARE
      clinical trial (n = 60). AEs, namely hematologic (hemoglobin, neutrophil and
      platelet counts), hepatic (alanine transaminase or bilirubin) and renal (eGFR),
      were measured according to the DAIDS toxicity table (version 1.0). RESULTS:
      BOC/IFN/RBV was associated with significantly more AEs, most commonly
      neutropenia, anemia and thrombocytopenia. In the SOF/RBV cohort, five (8 %)
      patients discontinued treatment early, but none (0 %) were because of AEs, while
      60 (62 %) patients on triple therapy discontinued treatment early, 34 (57 %)
      because of AEs. SVR24 rates were 68 versus 34 % with SOF/RBV versus BOC/IFN/RBV.
      CONCLUSIONS: SOF/RBV treatment was associated with fewer side effects than BOC
      based triple therapy, appearing to be a safer and more tolerable alternative for
      HCV GT-1 subjects. These results show that emerging IFN-free therapies may
      enhance patient adherence, allowing treatment of larger number of patients with
      improved efficacy.

PMID- 26202762
TI  - Interobserver reproducibility of the controlled attenuation parameter (CAP) for
      quantifying liver steatosis.
AB  - PURPOSE: This study was conducted to prospectively investigate the interobserver
      reproducibility of controlled attenuation parameter (CAP) measurements and the
      relationship among the CAP and body mass index (BMI), gender and age. METHODS:
      Consecutive subjects were studied using the M+ probe of the FibroScan device
      (Echosens, Paris, France). Measurements were performed by two raters (rater1 and
      rater2). Interobserver agreement was assessed by using the concordance
      correlation coefficient (CCC). The Pearson r coefficient was used to test
      correlation between two study variables, and linear regression was used for the
      multivariate model. RESULTS: Three hundred fifty-one subjects (227 males and 124
      females) were prospectively studied. The CCC was 0.82 (95 % CI 0.78-0.85)
      overall, 0.80 (95 % CI 0.75-0.85) for BMI <25 kg/m(2), 0.76 (95 % CI 0.69-0.84)
      for BMI 25-29 kg/m(2) and 0.65 (95 % CI 0.41-0.88) for BMI >=30 kg/m(2). The CCC
      was 0.44 (95 % CI 0.31-0.56) for CAP values <=240 dB/m and 0.72 (95 % CI 0.65
      0.79) for CAP values >240 dB/m. In univariate analysis, age and BMI by gender
      were correlated with the CAP. Multiple regression analysis confirmed the
      relationship of the CAP with age and BMI, but not with gender. CONCLUSIONS: The
      results of this study show that the interreader agreement in CAP measurement is
      good. In healthy volunteers, the CAP is strongly correlated with age and BMI.

PMID- 26202763
TI  - Clinical outcomes of spontaneous bacterial peritonitis due to extended-spectrum
      beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae: a
      retrospective cohort study.
AB  - PURPOSE: The aim of this study was to (1) evaluate the clinical outcomes of
      spontaneous bacterial peritonitis (SBP) due to extended-spectrum beta-lactamase
      (ESBL)-producing Escherichia coli or Klebsiella pneumoniae (EK) and (2)
      investigate the relationship between the adequacy of initial antibiotic
      treatments and patient outcomes. METHODS: We conducted a retrospective cohort
      study of cirrhotic patients with SBP caused by EK. We evaluated the 30-day
      mortality rate and used Cox proportional hazard models to identify risk factors
      for mortality. RESULTS: Between January 2006 and December 2012, a total of 231
      episodes of SBP due to EK were recorded. Among them, 52 were caused by ESBL
      producing EK (ESBL-EK). The 30-day mortality rate was significantly higher in
      patients with SBP due to ESBL-EK than in those with non-ESBL-producing EK (non
      ESBL-EK) (34.6 vs. 18.4 %, respectively; p = 0.013). Multivariate analysis
      revealed that ESBL production [adjusted HR (aHR) 1.82, 95 % confidence interval
      (CI) 1.00-3.31], nosocomial infection (aHR 2.24, 95 % CI 1.26-3.95), septic shock
      (aHR 4.84, 95 % CI 2.70-8.65), higher Child-Pugh score (aHR 1.57, 95 % CI 1.28
      1.92), and higher Charlson comorbidity index (aHR 1.37, 95 % CI 1.15-1.64) were
      independent risk factors for 30-day mortality in the total cohort. When we
      analyzed patients with SBP due to ESBL-EK separately, septic shock (aHR 3.64, 95
      % CI 1.40-9.77), accompanying bacteremia (aHR 3.71, 95 % CI 1.37-10.08), and
      hepatocellular carcinoma (aHR 3.21, 95 % CI 1.20-8.56) were independent risk
      factors. CONCLUSIONS: Both 7- and 30-day mortalities for SBP due to ESBL-EK were
      significantly higher than for SBP due to non-ESBL-EK. Initial antibiotic choice
      was not associated with poor clinical outcomes in patients with SBP due to ESBL
      EK.

PMID- 26202764
TI  - Diastolic cardiac dysfunction is a predictor of dismal prognosis in patients with
      liver cirrhosis.
AB  - BACKGROUND AND PURPOSE: Left ventricular diastolic dysfunction (LVDD) constitutes
      the prominent characteristic of cirrhotic cardiomyopathy, but its relevance on
      the clinical course of cirrhotic patients has not been clearly defined. The aim
      of the study was to evaluate the relationship of LVDD with the severity and
      etiology of liver disease and to investigate whether it affects the outcome of
      cirrhotic patients. METHODS: Cardiac function of 45 cirrhotics was studied by a
      tissue Doppler imaging echocardiography. Diagnosis of LVDD was made according to
      the latest guidelines of the American Society of Echocardiography. All patients
      were followed up for a period of 2 years. Death or liver transplantation was the
      endpoint of the study. RESULTS: LVDD was found in 17 (38 %) of 45 patients. Its
      presence was not found to be associated with the etiology and stage of cirrhosis,
      but its severity was directly correlated with the Child-Pugh score. At the end of
      follow-up, 14 patients had died; 9 had LVDD (9/17, 53 %) and 5 had not (5/28, 18
      %). Patients who died at the beginning of observation period had a higher Child
      Pugh and MELD score, higher BNP, lower albumin and more prolonged QTc. On Kaplan
      Meier analysis, patients with LVDD had statistically significantly worse
      prognosis compared to those without (p = 0.013, log rank: 5.495). Low albumin
      values (p = 0.003) and presence of LVDD (p = 0.017) were independent predictive
      factors of mortality. CONCLUSIONS: LVDD is a common complication of cirrhosis. As
      its development seems to be related to a worse prognosis, patients with LVDD must
      be under a strict follow-up.

PMID- 26202765
TI  - Erratum to: Yttrium-90 radioembolization for hepatocellular carcinoma in
      hepatitis B: commentary on a 103-patient Asian cohort.

PMID- 26202766
TI  - Adoptive T-cell therapy for cancer: The era of engineered T cells.
AB  - Tumors originate from a number of genetic events that deregulate homeostatic
      mechanisms controlling normal cell behavior. The immune system, devoted to patrol
      the organism against pathogenic events, can identify transformed cells, and in
      several cases cause their elimination. It is however clear that several
      mechanisms encompassing both central and peripheral tolerance limit antitumor
      immunity, often resulting into progressive diseases. Adoptive T-cell therapy with
      either allogeneic or autologous T cells can transfer therapeutic immunity. To
      date, genetic engineering of T cells appears to be a powerful tool for shaping
      tumor immunity. In this review, we discuss the most recent achievements in the
      areas of suicide gene therapy, and TCR-modified T cells and chimeric antigen
      receptor gene-modified T cells. We provide an overview of current strategies
      aimed at improving the safety and efficacy of these approaches, with an outlook
      on prospective developments.

PMID- 26202767
TI  - Clinical impact of high-attenuation and cystic areas on computed tomography in
      fibrotic idiopathic interstitial pneumonias.
AB  - BACKGROUND: Quantitative computed tomography (CT) analysis has been proposed as a
      means of objectively assessing fibrotic interstitial pneumonia (IP) including
      idiopathic pulmonary fibrosis (IPF). We investigated whether percentages of high
      attenuation areas (HAA%) and cystic areas (CA%) quantified from CT images were
      useful as indices of fibrotic IP. METHODS: CT images of 74 patients with fibrotic
      idiopathic interstitial pneumonias (IPF, 36; non-specific interstitial pneumonia,
      9; unclassifiable idiopathic interstitial pneumonia, 29) were analyzed via in
      house computer software, which automatically calculated HAA%, CA%, mean lung
      density (MLD), standard deviation of lung density (SD-LD), kurtosis, and skewness
      from CT attenuation histograms. These indices were compared in each instance with
      physiologic measures, visual fibrosis score, clinical diagnosis, radiologic CT
      pattern, and prognosis. RESULTS: HAA% correlated significantly with physiologic
      measures and visual fibrosis score to a moderate extent (%forced vital capacity,
      rs = -0.59; % carbon monoxide diffusion capacity, rs = -0.43; fibrosis score, rs
      = 0.23). Densitometric parameters (MLD, SD-LD, kurtosis, and skewness) correlated
      significantly with physiologic measures and fibrosis score (|rs| = 0.28-0.59).
      CA% showed no association with pulmonary functions but differed significantly
      between IPF and other interstitial pneumonias (IPs) (1.50 +/- 2.41% vs. 0.41 +/-
      0.80%; P < 0.01) and between the definite usual interstitial pneumonia (UIP)
      pattern and other patterns (1.48 +/- 2.38% vs. 0.55 +/- 1.19%; P < 0.01). On
      univariate analysis, HAA%, MLD, SD-LD, kurtosis, skewness, fibrosis score, and
      definite UIP pattern all correlated with survival, with kurtosis alone identified
      as a significant predictor of mortality on multivariate analysis (hazard ratio =
      0.67; 95% CI, 0.44-0.96; P = 0.03). CONCLUSION: CA% and HAA% are novel
      quantitative CT indices with differing properties in fibrotic IP evaluations.
      HAA% largely reflects physiologic impairments, whereas CA% corresponds with
      diagnosis and HRCT pattern. Of the CT indices examined, kurtosis constituted the
      strongest predictor of mortality.

PMID- 26202769
TI  - Gender differences in rates of carriage and bloodstream infection caused by
      methicillin-resistant Staphylococcus aureus: are they real, do they matter and
      why?
AB  - There is increasing interest in sexual and gender dimorphism in disease. We
      reviewed the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA)
      carriage and bloodstream infection (BSI), which shows a male predominance, and
      explored some of the possible reasons. Males are more prone to bacterial sepsis,
      but some studies suggest females may have a poorer prognosis from BSI. Hand
      hygiene behavior varies according to gender. Males are less compliant, which in
      turn may predispose them to higher colonization and infection rates. Female
      hormones such as estrogen affect the expression of virulence factors in
      Pseudomonas aeruginosa, and although not studied, this may also apply to S.
      aureus. Further research is required on the relationship between gender and risk
      of infection, the reasons for higher MRSA carriage and BSI rates in males, the
      value of gender-specific infection prevention campaigns, and other factors such
      as the possible role of contact sports and occupation. 

PMID- 26202770
TI  - US poll finds strong support for Medicare and Medicaid.

PMID- 26202768
TI  - Maraviroc Pharmacokinetics in HIV-1-Infected Pregnant Women.
AB  - OBJECTIVE: To describe the pharmacokinetics of maraviroc in human
      immunodeficiency virus (HIV)-infected women during pregnancy and post partum.
      METHODS: HIV-infected pregnant women receiving maraviroc as part of clinical care
      had intensive steady-state 12-hour pharmacokinetic profiles performed during the
      third trimester and >=2 weeks after delivery. Cord blood samples and matching
      maternal blood samples were taken at delivery. The data were collected in 2
      studies: P1026 (United States) and PANNA (Europe). Pharmacokinetic parameters
      were calculated. RESULTS: Eighteen women were included in the analysis. Most
      women (12; 67%) received 150 mg of maraviroc twice daily with a protease
      inhibitor, 2 (11%) received 300 mg twice daily without a protease inhibitor, and
      4 (22%) had an alternative regimen. The geometric mean ratios for third-trimester
      versus postpartum maraviroc were 0.72 (90% confidence interval, .60-.88) for the
      area under the curve over a dosing interval (AUCtau) and 0.70 (0.58-0.85) for the
      maximum maraviroc concentration. Only 1 patient showed a trough concentration
      (Ctrough) below the suggested target of 50 ng/mL, both during pregnancy and post
      partum. The median ratio of maraviroc cord blood to maternal blood was 0.33
      (range, 0.03-0.56). The viral load close to delivery was <50 copies/mL in 13
      women (76%). All children were HIV negative at testing. CONCLUSIONS: Overall
      maraviroc exposure during pregnancy was decreased, with a reduction in AUCtau and
      maximum concentration of about 30%. Ctrough was reduced by 15% but exceeded the
      minimum Ctrough target concentration. Therefore, the standard adult dose seems
      sufficient in pregnancy. CLINICAL TRIALS REGISTRATION: NCT00825929 and
      NCT000422890.

PMID- 26202772
TI  - Lost in Translation: Adapting a Face-to-Face Course Into an Online Learning
      Experience.
AB  - Online education has grown dramatically over the past decade. Instructors who
      teach face-to-face courses are being called on to adapt their courses to the
      online environment. Many instructors do not have sufficient training to be able
      to effectively move courses to an online format. This commentary discusses the
      growth of online learning, common challenges faced by instructors adapting
      courses from face-to-face to online, and best practices for translating face-to
      face courses into online learning opportunities. 

PMID- 26202771
TI  - Heroin-related overdose: The unexplored influences of markets, marketing and
      source-types in the United States.
AB  - Heroin overdose, more accurately termed 'heroin-related overdose' due to the
      frequent involvement of other drugs, is the leading cause of mortality among
      regular heroin users. (Degenhardt et al., 2010) Heroin injectors are at greater
      risk of hospital admission for heroin-related overdose (HOD) in the eastern
      United States where Colombian-sourced powder heroin is sold than in the western
      US where black 'tar' heroin predominates. (Unick et al., 2014) This paper
      examines under-researched influences on HOD, both fatal and non-fatal, using data
      from a qualitative study of injecting drug users of black tar heroin in San
      Francisco and powder heroin in Philadelphia Data were collected through in-depth,
      semi-structured interviews carried out in 2012 that were conducted against a
      background of longer-term participant-observation, ethnographic studies of drug
      users and dealers in Philadelphia (2007-12) and of users in San Francisco (1994
      2007, 2012). Our findings suggest three types of previously unconsidered
      influences on overdose risk that arise both from structural socio-economic
      factors and from the physical properties of the heroin source-types: 1) retail
      market structure including information flow between users; 2) marketing
      techniques such as branding, free samples and pricing and 3) differences in the
      physical characteristics of the two major heroin source forms and how they affect
      injecting techniques and vascular health. Although chosen for their contrasting
      source-forms, we found that the two cities have contrasting dominant models of
      drug retailing: San Francisco respondents tended to buy through private dealers
      and Philadelphia respondents frequented an open-air street market where heroin is
      branded and free samples are distributed, although each city included both types
      of drug sales. These market structures and marketing techniques shape the
      availability of information regarding heroin potency and its dissemination among
      users who tend to seek out the strongest heroin available on a given day. The
      physical characteristics of these two source-types, the way they are prepared for
      injecting and their effects on vein health also differ markedly. The purpose of
      this paper is to examine some of the unexplored factors that may lead to heroin
      related overdose in the United States and to generate hypotheses for further
      study. 

PMID- 26202773
TI  - A Community-Engaged Research Approach to Improve Mental Health Among Latina
      Immigrants: ALMA Photovoice.
AB  - Recent Latina immigrants are at increased risk of poor mental health due to
      stressors associated with adapting to life in the United States. Existing social
      and health care policies often do not adequately address the mental health
      concerns of new Latino populations. Amigas Latinas Motivando el Alma, a community
      partnered research project, seeks to improve immigrant Latinas' mental health
      outcomes. Using Photovoice methodology, promotoras (lay health advisors)
      reflected on community factors affecting mental health through photography and
      guided discussion. Discussions were audio-recorded, transcribed, and coded using
      content analysis to identify salient themes. Promotoras reviewed codes to develop
      themes that they presented in community forums to reach local policy makers and
      to increase community awareness. These forums included an exhibit of the
      promotoras' photographs and discussion of action steps to address community
      concerns. Themes included transitioning to life in the United States, parenting,
      education, and combating racism. Nearly 150 stakeholders attended the community
      forums and proposed responses to promotoras' photographic themes. Our findings
      suggest that Photovoice provides an opportunity for Latinas and the larger
      community to identify issues that they find most important and to explore avenues
      for action and change by creating sustainable partnerships between the community
      and forum attendees.

PMID- 26202774
TI  - Contexts for Sustainable Implementation of a Colorectal Cancer Screening Program
      at a Community Health Center.
AB  - BACKGROUND: "Context" is a mediating construct that significantly influences the
      initiation and maintenance of program implementation, but it has seldom been
      studied in process evaluation. This case study describes the contextual factors
      that encourage or impede the implementation processes of a research-tested
      program at a Federally Qualified Community Health Center. METHOD: We conducted 14
      key informant interviews with providers, nurses, medical assistants, and clinic
      staff in leadership and management positions during the 24 months of active
      implementation. Interview data were analyzed using Atlas.ti software. A written
      log documenting exposure, adherence, and coverage of the implementation was used
      to describe implementation fidelity. RESULTS: Findings indicated that program
      implementation needs to align with the organization's mission and values.
      Sensemaking caused individuals to understand the importance of the new process
      and increased their motivation to follow assigned procedures. Revisions of the
      implementation process allowed the program to fit better with the clinic's
      existing workflow. However, permitting flexibility in the delivery of an
      intervention may result in inconsistent implementation fidelity. In this study,
      threats to implementation included unanticipated changes in the clinic
      environment, such as budget cuts to resources and staff turnover as a consequence
      of the current economic downturn. CONCLUSIONS: Momentum leading to sustainable
      implementation requires a continuous team effort and a stable environment;
      consequently, a successful implementation requires a structure that supports
      problem solving, communication, and evaluation.

PMID- 26202775
TI  - DeVries: the Art of not freezing fish.

PMID- 26202776
TI  - Sprint sensitivity and locomotor trade-offs in green anole (Anolis carolinensis)
      lizards.
AB  - How well an organism completes an ecologically relevant task - its performance -
      is often considered a key factor in determining individual fitness. Historically,
      ecomorphological studies have examined how morphological traits determine
      individual performance in a static manner, assuming that differential fitness in
      a population is due indirectly to differences in morphological traits that
      determine a simple measure of performance. This assumption, however, ignores many
      ecological factors that can constrain performance in nature, such as substrate
      variation and individual behavior. We examined some of these complexities in the
      morphology-performance-fitness paradigm, primarily the impact that substrate
      variation has on performance. We measured maximal sprint speed of green anole
      lizards on four substrates that varied in size and complexity and are used by or
      available to individuals in nature. Performance decreased significantly from a
      broad substrate to a narrow substrate, and lizards were three times slower on a
      complex substrate than the broadest substrate. We also detected trade-offs in
      running on substrates with different diameters and in cluttered versus
      uncluttered environments. Furthermore, morphological predictors of performance
      varied among substrates. This indicates that natural selection may act on
      different morphological traits, depending on which substrates are used by
      individuals, as well as an individual's ability to cope with changes in substrate
      rather than maximal capacities. 

PMID- 26202777
TI  - Flight-motor-driven respiratory airflow increases tracheal oxygen to nearly
      atmospheric level in blowflies (Calliphora vicina).
AB  - It is widely accepted that an efficient oxygen supply and removal of CO2 in small
      flying insects are sufficiently performed by diffusion with open spiracles. This
      paper shows that in the tethered flying blowfly, gas exchange occurs by
      autoventilation and unidirectional airflow. The air is inspired through the
      mesothoracic spiracles (Sp1) during the downstroke of the wings and is expired
      through the metathoracic spiracles (Sp2) during the upstroke. This directed
      airflow through the thoracic tracheal system was documented by pre-atrial
      pressure measurements at the Sp1 and Sp2, revealing a sub-atmospheric mean
      pressure at the Sp1 and an over-atmospheric mean pressure at the Sp2. In the
      mesothoracic air sacs, the mean pressure is sub-atmospheric, conditioned by the
      only slightly open spiracles. In a split flow-through chamber experiment, the CO2
      released through the Sp2 confirmed this unidirectional respiratory gas flow,
      implicating an inner tracheal valve. In the thoracic tracheal system, the PO2 
      during flight exceeds the high resting PO2  by 1-2 kPa, reaching nearly
      atmospheric values. In the abdominal large air sacs, the PO2  drops during
      flight, probably due to the accumulation of CO2. Periodic heartbeat reversals
      continue during flight, with a higher period frequency than at rest, supporting
      the transport of CO2 via the haemolymph towards the metathoracic tracheae and
      abdominal air sacs. 

PMID- 26202778
TI  - How to know which food is good for you: bumblebees use taste to discriminate
      between different concentrations of food differing in nutrient content.
AB  - In view of the ongoing pollinator decline, the role of nutrition in bee health
      has received increasing attention. Bees obtain fat, carbohydrates and protein
      from pollen and nectar. As both excessive and deficient amounts of these
      macronutrients are detrimental, bees would benefit from assessing food quality to
      guarantee an optimal nutrient supply. While bees can detect sucrose and use it to
      assess nectar quality, it is unknown whether they can assess the macronutrient
      content of pollen. Previous studies have shown that bees preferentially collect
      pollen of higher protein content, suggesting that differences in pollen quality
      can be detected either by individual bees or via feedback from larvae. In this
      study, we examined whether and, if so, how individuals of the buff-tailed
      bumblebee (Bombus terrestris) discriminate between different concentrations of
      pollen and casein mixtures and thus nutrients. Bumblebees were trained using
      absolute and differential conditioning of the proboscis extension response (PER).
      As cues related to nutrient concentration could theoretically be perceived by
      either smell or taste, bees were tested on both olfactory and, for the first
      time, chemotactile perception. Using olfactory cues, bumblebees learned and
      discriminated between different pollen types and casein, but were unable to
      discriminate between different concentrations of these substances. However, when
      they touched the substances with their antennae, using chemotactile cues, they
      could also discriminate between different concentrations. Bumblebees are
      therefore able to discriminate between foods of different concentrations using
      contact chemosensory perception (taste). This ability may enable them to
      individually regulate the nutrient intake of their colonies. 

PMID- 26202779
TI  - Snake constriction rapidly induces circulatory arrest in rats.
AB  - As legless predators, snakes are unique in their ability to immobilize and kill
      their prey through the process of constriction, and yet how this pressure
      incapacitates and ultimately kills the prey remains unknown. In this study, we
      examined the cardiovascular function of anesthetized rats before, during and
      after being constricted by boas (Boa constrictor) to examine the effect of
      constriction on the prey's circulatory function. The results demonstrate that
      within 6 s of being constricted, peripheral arterial blood pressure (PBP) at the
      femoral artery dropped to 1/2 of baseline values while central venous pressure
      (CVP) increased 6-fold from baseline during the same time. Electrocardiographic
      recordings from the anesthetized rat's heart revealed profound bradycardia as
      heart rate (fH) dropped to nearly half of baseline within 60 s of being
      constricted, and QRS duration nearly doubled over the same time period. By the
      end of constriction (mean 6.5+/-1 min), rat PBP dropped 2.9-fold, fH dropped 3.9
      fold, systemic perfusion pressure (SPP=PBP-CVP) dropped 5.7-fold, and 91% of rats
      (10 of 11) had evidence of cardiac electrical dysfunction. Blood drawn
      immediately after constriction revealed that, relative to baseline, rats were
      hyperkalemic (serum potassium levels nearly doubled) and acidotic (blood pH
      dropped from 7.4 to 7.0). These results are the first to document the
      physiological response of prey to constriction and support the hypothesis that
      snake constriction induces rapid prey death due to circulatory arrest. 

PMID- 26202780
TI  - Intentional fatal metallic phosphide poisoning in a dog--a case report.
AB  - BACKGROUND: Metallic phosphides are extremely toxic pesticides that are regulated
      in their usage. Information concerning the impact of metallic phosphides on human
      health is abundant. Data regarding the clinical pathology of phosphide poisoning
      in humans or domestic and wild animals is largely incomplete with only a few
      cases of metallic phosphide poisoning being reported every year, especially in
      humans. For the majority of cases reported in dogs the data are vague or
      incomplete. Here we report a complete and detailed description of pathological
      changes in a case of intentional metallic phosphide poisoning in a dog including
      an exhaustive examination of the brain. CASE PRESENTATION: A 1 year old, male,
      Belgian Shepherd crossbreed dog with a clean medical history and no observed
      clinical signs prior to death, was submitted for post mortem examination. The dog
      was found dead by the owner. Near the body a suspect mix of bread, fat and a
      blackish powder was found. The owner announced the authorities and submitted the
      animal and the possible bait for forensic examination. At necropsy, multisystemic
      necrotic and degenerative lesions were observed. Histological exam confirmed the
      presence of necrotic and degenerative lesions of variable severity in all of the
      examined organs. The toxicological forensic examination revealed the presence of
      the phosphine gas in the gastric content and the bait. CONCLUSION: Metallic
      phosphide poisoning is a rarely reported entity, since the diagnosis of
      intentional poisoning with these compounds is a great challenge for forensic
      pathologists and toxicologists. To our knowledge, this is the first study
      describing the lesions completely in veterinary forensic toxicology. We assume
      that the toxic shows systemic endotheliotropism and damage of the endothelial
      cells responsible for the hemorrhagic lesions and for the secondary ischemic
      necrosis in various organs. This report will contribute to a better understanding
      of the pathogenesis in cases of acute metallic phosphide exposure in animals.

PMID- 26202781
TI  - Three-dimensional plotting of a cell-laden alginate/methylcellulose blend:
      towards biofabrication of tissue engineering constructs with clinically relevant
      dimensions.
AB  - Biofabrication of tissue engineering constructs with tailored architecture and
      organized cell placement using rapid prototyping technologies is a major research
      focus in the field of regenerative therapies. This study describes a novel
      alginate-based material suitable for both cell embedding and fabrication of three
      dimensional (3D) structures with predefined geometry by 3D plotting. The
      favourable printing properties of the material were achieved by using a simple
      strategy: addition of methylcellulose (MC) to a 3% alginate solution resulted in
      a strongly enhanced viscosity, which enabled accurate and easy deposition without
      high technical efforts. After scaffold plotting, the alginate chains were
      crosslinked with Ca2+ ; MC did not contribute to the gelation and was released
      from the scaffolds during the following cultivation. The resulting constructs are
      characterized by high elasticity and stability, as well as an enhanced
      microporosity caused by the transient presence of MC. The suitability of the
      alginate/MC blend for cell embedding was evaluated by direct incorporation of
      mesenchymal stem cells during scaffold fabrication. The embedded cells showed
      high viability after 3 weeks of cultivation, which was similar to those of cells
      within pure alginate scaffolds which served as control. Maintenance of the
      differentiation potential of embedded cells, as an important requirement for the
      generation of functional tissue engineering constructs, was proven for adipogenic
      differentiation as a model for soft tissue formation. In conclusion, the
      temporary integration of MC into a low-concentrated alginate solution allowed the
      generation of scaffolds with dimensions in the range of centimetres without loss
      of the positive properties of low-concentrated alginate hydrogels with regard to
      cell embedding. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26202782
TI  - Magnetic and luminescent properties of lanthanide coordination polymers with
      asymmetric biphenyl-3,2',5'-tricarboxylate.
AB  - Eight isostructural lanthanide coordination polymers [Ln(bptc)(phen)(H2O)]n (Ln =
      Dy for , Eu for , Tb for , Gd for , Sm for , Nd for , Yb for , Pr for ) were
      successfully prepared based on bridging asymmetric polycarboxylate ligand
      biphenyl-3,2',5'-tricarboxylic acid (H3bptc) and chelating 1,10-phenanthroline
      (phen) coligand. Single crystal X-ray analysis reveals that complexes have a
      (3,6)-connected CdI2-type coordination network consisting of paddle-wheel dimers
      [Ln2(CO2)4]. The magnetic and fluorescent properties of have been investigated.
      Significantly, the Dy(iii) complex behaves with slow relaxation of the
      magnetization, where the frequency-dependent out-of-phase signals are noticed. 

PMID- 26202784
TI  - Substitution of whole cows' milk with defatted milk for 4 months reduced serum
      total cholesterol, HDL-cholesterol and total apoB in a sample of Mexican school
      age children (6-16 years of age).
AB  - We carried out this study to compare the effect of consuming whole, partially
      defatted and defatted cows' milk for 4 months on serum concentrations of blood
      indicators of cardiovascular risk (CVR) in Mexican children and adolescents.
      Children aged between 6 and 16 years living in indigenous boarding schools in
      Mexico and who were usual consumers of whole milk were recruited to this study.
      Totally, thirteen boarding schools were randomly selected to receive full
      supplies of whole, partially defatted and defatted cows' milk for 4 months. Serum
      total cholesterol (TC), TAG, HDL-cholesterol, apoA and total apoB, and Lp(a)
      concentrations were measured before and after the intervention. Comparisons were
      made with multi-level mixed-effects linear regression models using the difference
      in differences approach. Compared with the whole milk group, TC, LDL-cholesterol,
      HDL-cholesterol and total apoB were lower in defatted milk consumers by -0.43, 
      0.28, -0.16 mmol/l and -0.05 g/l, respectively (all P<0.001). Compared with the
      whole milk group, the group that consumed partially defatted milk showed a
      significant decrease in the concentrations of LDL-cholesterol (-0.12, P=0.01),
      apoA (-0.05 g/l, P=0.01) and total apoB (-0.05 g/l, P=0.001). Defatted milk
      intake for 4 months reduced some of the serum indicators of CVR. 

PMID- 26202783
TI  - Deworming drugs for soil-transmitted intestinal worms in children: effects on
      nutritional indicators, haemoglobin, and school performance.
AB  - BACKGROUND: The World Health Organization (WHO) recommends treating all school
      children at regular intervals with deworming drugs in areas where helminth
      infection is common. As the intervention is often claimed to have important
      health, nutrition, and societal effects beyond the removal of worms, we
      critically evaluated the evidence on benefits. OBJECTIVES: To summarize the
      effects of giving deworming drugs to children to treat soil-transmitted helminths
      on weight, haemoglobin, and cognition; and the evidence of impact on physical
      well-being, school attendance, school performance, and mortality. SEARCH METHODS:
      We searched the Cochrane Infectious Diseases Group Specialized Register (14 April
      2015); Cochrane Central Register of Controlled Trials (CENTRAL), published in the
      Cochrane Library (2015, Issue 4); MEDLINE (2000 to 14 April 2015); EMBASE (2000
      to 14 April 2015); LILACS (2000 to 14 April 2015); the metaRegister of Controlled
      Trials (mRCT); and reference lists, and registers of ongoing and completed trials
      up to 14 April 2015. SELECTION CRITERIA: We included randomized controlled trials
      (RCTs) and quasi-RCTs comparing deworming drugs for soil-transmitted helminths
      with placebo or no treatment in children aged 16 years or less, reporting on
      weight, haemoglobin, and formal tests of intellectual development. We also sought
      data on school attendance, school performance, and mortality. We included trials
      that combined health education with deworming programmes. DATA COLLECTION AND
      ANALYSIS: At least two review authors independently assessed the trials,
      evaluated risk of bias, and extracted data. We analysed continuous data using the
      mean difference (MD) with 95% confidence intervals (CIs). Where data were
      missing, we contacted trial authors. We used outcomes at time of longest follow
      up. The evidence quality was assessed using GRADE. This edition of the Cochrane
      Review adds the DEVTA trial from India, and draws on an independent analytical
      replication of a trial from Kenya. MAIN RESULTS: We identified 45 trials,
      including nine cluster-RCTs, that met the inclusion criteria. One trial
      evaluating mortality included over one million children, and the remaining 44
      trials included a total of 67,672 participants. Eight trials were in children
      known to be infected, and 37 trials were carried out in endemic areas, including
      areas of high (15 trials), moderate (12 trials), and low prevalence (10 trials).
      Treating children known to be infectedTreating children known to be infected with
      a single dose of deworming drugs (selected by screening, or living in areas where
      all children are infected) may increase weight gain over the next one to six
      months (627 participants, five trials, low quality evidence). The effect size
      varied across trials from an additional 0.2 kg gain to 1.3 kg. There is currently
      insufficient evidence to know whether treatment has additional effects on
      haemoglobin (247 participants, two trials, very low quality evidence); school
      attendance (0 trials); cognitive functioning (103 participants, two trials, very
      low quality evidence), or physical well-being (280 participants, three trials,
      very low quality evidence). Community deworming programmesTreating all children
      living in endemic areas with a dose of deworming drugs probably has little or no
      effect on average weight gain (MD 0.04 kg less, 95% CI 0.11 kg less to 0.04 kg
      more; trials 2719 participants, seven trials, moderate quality evidence), even in
      settings with high prevalence of infection (290 participants, two trials). A
      single dose also probably has no effect on average haemoglobin (MD 0.06 g/dL, 95%
      CI -0.05 lower to 0.17 higher; 1005 participants, three trials, moderate quality
      evidence), or average cognition (1361 participants, two trials, low quality
      evidence).Similiarly, regularly treating all children in endemic areas with
      deworming drugs, given every three to six months, may have little or no effect on
      average weight gain (MD 0.08 kg, 95% CI 0.11 kg less to 0.27 kg more; 38,392
      participants, 10 trials, low quality evidence). The effects were variable across
      trials; one trial from a low prevalence setting carried out in 1995 found an
      increase in weight, but nine trials carried out since then found no effect,
      including five from moderate and high prevalence areas.There is also reasonable
      evidence that regular treatment probably has no effect on average height (MD 0.02
      cm higher, 95% CI 0.14 lower to 0.17 cm higher; 7057 participants, seven trials,
      moderate quality evidence); average haemoglobin (MD 0.02 g/dL lower; 95% CI 0.08
      g/dL lower to 0.04 g/dL higher; 3595 participants, seven trials, low quality
      evidence); formal tests of cognition (32,486 participants, five trials, moderate
      quality evidence); exam performance (32,659 participants, two trials, moderate
      quality evidence); or mortality (1,005,135 participants, three trials, low
      quality evidence). There is very limited evidence assessing an effect on school
      attendance and the findings are inconsistent, and at risk of bias (mean
      attendance 2% higher, 95% CI 4% lower to 8% higher; 20,243 participants, two
      trials, very low quality evidence).In a sensitivity analysis that only included
      trials with adequate allocation concealment, there was no evidence of any effect
      for the main outcomes. AUTHORS' CONCLUSIONS: Treating children known to have worm
      infection may have some nutritional benefits for the individual. However, in mass
      treatment of all children in endemic areas, there is now substantial evidence
      that this does not improve average nutritional status, haemoglobin, cognition,
      school performance, or survival.

PMID- 26202786
TI  - Dexmedetomidine for tracheal extubation in deeply anesthetized adult patients
      after otologic surgery: a comparison with remifentanil.
AB  - BACKGROUND: Remifentanil and dexmedetomidine are well known to suppress airway
      reflexes during airway procedures. Smooth tracheal extubation is important after
      otologic surgery. The purpose of this study is to compare the effectiveness of
      dexmedetomidine or remifentanil infusion for producing smooth tracheal extubation
      in deeply anesthetized patients after otologic surgery. METHODS: Seventy-four ASA
      I-II adult patients (18-60 years old) scheduled for elective otologic surgery
      were randomly assigned to one of three groups: sevoflurane-remifentanil (Group
      SR, n = 25), sevoflurane-dexmedetomidine (0.5 MUg/kg) (Group SD5, n = 24), or
      sevoflurane-dexmedetomidine (0.7 MUg/kg) (Group SD7, n = 25). Remifentanil or
      dexmedetomidine were administered for 10 min at the end of surgery. The primary
      outcome was the rate of smooth extubation. Respiratory pattern, airway
      obstruction, hemodynamic and respiratory profiles, time to awake, rescue
      analgesics in the post-anesthesia care unit (PACU), and postoperative nausea and
      vomiting (PONV) were also recorded. RESULTS: The rate of smooth tracheal
      extubation as defined 1 min post-extubation was the same for Groups SR and SD7 (P
      > 0.05), but the rate of smooth extubation was lower for Group SD5 than for the
      other two groups (p < 0.05). During extubation, the respiratory rate was lower in
      Group SR than in both dexmedetomidine groups (p < 0.05). The hemodynamic profiles
      at extubation were similar between groups (p > 0.05), but the mean arterial
      pressure and heart rate were higher in Group SR at 10 and 15 min after extubation
      (p < 0.05). The incidence of airway obstruction and time to awake were comparable
      for all groups (p > 0.05). The need for rescue analgesic in the PACU was more
      common in Group SR than in both dexmedetomidine groups (P < 0.01). Compared to
      Group SR, both dexmedetomidine groups had less PONV on postoperative day 1 (p <
      0.05). CONCLUSION: Combined with 1 MAC sevoflurane, dexmedetomidine 0.7 ug/kg and
      remifentanil provided similar rates for smooth tracheal extubation in
      spontaneously breathing, anesthetized adults. Dexmedetomidine exhibited opioid
      sparing effects postoperatively and was associated with less PONV than
      remifentanil.

PMID- 26202785
TI  - Toll pathway modulates TNF-induced JNK-dependent cell death in Drosophila.
AB  - Signalling networks that control the life or death of a cell are of central
      interest in modern biology. While the defined roles of the c-Jun N-terminal
      kinase (JNK) pathway in regulating cell death have been well-established,
      additional factors that modulate JNK-mediated cell death have yet to be fully
      elucidated. To identify novel regulators of JNK-dependent cell death, we
      performed a dominant-modifier screen in Drosophila and found that the Toll
      pathway participates in JNK-mediated cell death. Loss of Toll signalling
      suppresses ectopically and physiologically activated JNK signalling-induced cell
      death. Our epistasis analysis suggests that the Toll pathway acts as a downstream
      modulator for JNK-dependent cell death. In addition, gain of JNK signalling
      results in Toll pathway activation, revealed by stimulated transcription of
      Drosomycin (Drs) and increased cytoplasm-to-nucleus translocation of Dorsal.
      Furthermore, the Spatzle (Spz) family ligands for the Toll receptor are
      transcriptionally upregulated by activated JNK signalling in a non-cell
      autonomous manner, providing a molecular mechanism for JNK-induced Toll pathway
      activation. Finally, gain of Toll signalling exacerbates JNK-mediated cell death
      and promotes cell death independent of caspases. Thus, we have identified another
      important function for the evolutionarily conserved Toll pathway, in addition to
      its well-studied roles in embryonic dorso-ventral patterning and innate immunity.

PMID- 26202787
TI  - Health literacy-listening skill and patient questions following cancer prevention
      and screening discussions.
AB  - OBJECTIVE: Patient question-asking is essential to shared decision making. We
      sought to describe patients' questions when faced with cancer prevention and
      screening decisions, and to explore differences in question-asking as a function
      of health literacy with respect to spoken information (health literacy
      listening). METHODS: Four-hundred and thirty-three (433) adults listened to
      simulated physician-patient interactions discussing (i) prophylactic tamoxifen
      for breast cancer prevention, (ii) PSA testing for prostate cancer and (iii)
      colorectal cancer screening, and identified questions they would have. Health
      literacy-listening was assessed using the Cancer Message Literacy Test-Listening
      (CMLT-Listening). Two authors developed a coding scheme, which was applied to all
      questions. Analyses examined whether participants scoring above or below the
      median on the CMLT-Listening asked a similar variety of questions. RESULTS:
      Questions were coded into six major function categories: risks/benefits,
      procedure details, personalizing information, additional information, decision
      making and credibility. Participants who scored higher on the CMLT-Listening
      asked a greater variety of risks/benefits questions; those who scored lower asked
      a greater variety of questions seeking to personalize information. This
      difference persisted after adjusting for education. CONCLUSION: Patients' health
      literacy-listening is associated with distinctive patterns of question
      utilization following cancer screening and prevention counselling. Providers
      should not only be responsive to the question functions the patient favours, but
      also seek to ensure that the patient is exposed to the full range of information
      needed for shared decision making.

PMID- 26202790
TI  - Stethoscope Hygiene: Practice and Attitude of Medical Students.
AB  - OBJECTIVE: The purpose of this study was to evaluate the frequency and attitude
      of medical students towards cleaning their stethoscopes. SUBJECTS AND METHODS: A
      cross-sectional study was carried out in the first week of December 2013. The
      study included 771 students (397 in their fourth and 374 in their sixth year)
      from the Faculty of Medicine, University of Belgrade, Serbia. An anonymous
      questionnaire was distributed to students before the start of compulsory lessons
      in classrooms. RESULTS: 317 of the 397 fourth-year students (79.8%) and 306 of
      the 374 sixth-year students (81.9%) cleaned their stethoscope. The stethoscope
      diaphragm was most commonly cleaned, while the flexible tubing was the least
      commonly cleaned area, mainly using ethyl alcohol-based agents. The strongest
      positive attitude was observed for the statement 'It is important that my
      stethoscope is clean' (4.3 out of 5.0). A positive correlation (Spearman's x03C1;
      = 0.105) was observed between a higher frequency of cleaning and the stronger
      positive notion that a stethoscope should be cleaned. CONCLUSION: A considerably
      high proportion of the students studied had ever cleaned their stethoscopes.
      Based on the students' responses, it would be useful to implement instructions on
      stethoscope hygiene in the regular practical curriculum with the aim of applying
      stethoscope disinfection in daily work.

PMID- 26202788
TI  - Combining radiotherapy with sunitinib: lessons (to be) learned.
AB  - To improve the efficacy of radiotherapy (RTx), there is a growing interest in
      combining RTx with drugs that inhibit angiogenesis, i.e., the process of neo
      vessel formation out of preexisting capillaries. A frequently used drug to
      inhibit angiogenesis is sunitinib (Sutent, SU11248), a receptor tyrosine kinase
      inhibitor that is currently FDA approved for the treatment of several cancer
      types. The current review presents an overview of the preclinical studies and
      clinical trials that combined sunitinib with RTx. We discuss the findings from
      preclinical and clinical observations with a focus on dose scheduling and
      commonly reported toxicities. In addition, the effects of combination therapy on
      tumor response and patient survival are described. Finally, the lessons learned
      from preclinical and clinical studies are summarized and opportunities and
      pitfalls for future clinical trials are presented. 

PMID- 26202789
TI  - Adverse events associated with poor neurological outcome during targeted
      temperature management and advanced critical care after out-of-hospital cardiac
      arrest.
AB  - INTRODUCTION: The aim of this study was to investigate the association of adverse
      events (AEs) during targeted temperature management (TTM) and other AEs and
      concomitant treatments during the advanced critical care period with poor
      neurological outcome at hospital discharge in adult out-of-hospital cardiac
      arrest (OHCA) patients. METHODS: This was a retrospective study using Korean
      Hypothermia Network registry data of adult OHCA patients treated with TTM in 24
      teaching hospitals throughout South Korea from 2007 to 2012. Demographic
      characteristics, resuscitation and post-resuscitation variables, AEs, and
      concomitant treatments during TTM and the advanced critical care were collected.
      The primary outcome was poor neurological outcome, defined as a cerebral
      performance category (CPC) score of 3-5 at hospital discharge. The AEs and
      concomitant treatments were individually entered into the best multivariable
      predictive model of poor neurological outcome to evaluate the associations
      between each variable and outcome. RESULTS: A total of 930 patients, including
      704 for whom a complete dataset of AEs and covariates was available for
      multivariable modeling, were included in the analysis; 476 of these patients
      exhibited poor neurological outcome [CPC 3 = 50 (7.1%), CPC 4 = 214 (30.4%), and
      CPC 5 = 212 (30.1%)]. Common AEs included hyperglycemia (45.6%), hypokalemia
      (31.3%), arrhythmia (21.3%) and hypotension (29%) during cooling, and hypotension
      (21.6%) during rewarming. Bleeding (5%) during TTM was a rare AE. Common AEs
      during the advanced critical care included pneumonia (39.6%), myoclonus (21.9%),
      seizures (21.7%) and hypoglycemia within 72 hours (23%). After adjusting for
      independent predictors of outcome, cooling- and rewarming-related AEs were not
      significantly associated with poor neurological outcome. However, sepsis,
      myoclonus, seizure, hypoglycemia within 72 hours and anticonvulsant use during
      the advanced critical care were associated with poor neurological outcome
      [adjusted odds ratios (95% confidence intervals) of 3.12 (1.40-6.97), 3.72 (1.93
      7.16), 4.02 (2.04-7.91), 2.03 (1.09-3.78), and 1.69 (1.03-2.77), respectively].
      Alternatively, neuromuscular blocker use was inversely associated with poor
      neurological outcome (0.48 [0.28-0.84]). CONCLUSIONS: Cooling- and rewarming
      related AEs were not associated with poor neurological outcome at hospital
      discharge. Sepsis, myoclonus, seizure, hypoglycemia within 72 hours and
      anticonvulsant use during the advanced critical care period were associated with
      poor neurological outcome at hospital discharge in our study.

PMID- 26202792
TI  - 23rd Annual Conference of APASL March 12-15, 2014, Brisbane, Australia.

PMID- 26202791
TI  - Topical antibiotic ointment versus silver-containing foam dressing for second
      degree burns in swine.
AB  - OBJECTIVES: Second-degree burns are very common but their management is
      controversial. These burns may be treated with either topical antimicrobial
      agents or advanced occlusive dressings; however, there is no established
      treatment comparator for preclinical studies. This study was designed to
      determine which of two commonly used comparator therapies (a silver-containing
      advanced dressing or a topical antibiotic ointment) resulted in faster
      reepithelialization and less scarring. The hypothesis was that second-degree
      burns treated with a topical antimicrobial ointment would heal faster and with
      less scarring than those treated with a silver-containing occlusive foam dressing
      in a porcine model. METHODS: Deep partial-thickness burns were created on the
      flanks of three anesthetized female domestic pigs (20 to 25 kg) using a 150-g
      aluminum bar preheated in 80 degrees C water bath and applied to the skin for 20
      seconds using a force of 2 kg. The burn eschars were excised 48 hours later with
      an electric dermatome set at a depth of 0.75 mm. The wound beds were treated with
      a thin layer of triple-antibiotic petrolatum-based ointment (changed three times
      weekly) or a silver-containing foam dressing (changed once weekly). Full
      thickness punch biopsies were obtained at 9, 11, 14, 16, 18, and 21 days for
      determination of percentage complete wound reepithelialization and at 28 days for
      measurement of scar depth. RESULTS: At all dressing changes the wounds treated
      with the topical antibiotic appeared moist, while those treated with the silver
      based dressings appeared dry. At day 21 all wounds treated with the ointment were
      completely reepithelialized, while only 55% of those treated with the silver
      dressing were reepithelialized (p < 0.001). Scar depth at day 28 was also
      significantly less in wounds treated with the topical antibiotic ointment (4.3 mm
      vs. 5.1 mm, difference = 0.7 mm; 95% confidence interval [CI] = 0.1 to 1.4 mm).
      There was less scar contraction in wounds treated with the topical antibiotic
      compared with the silver-based dressing (mean +/- SD = 25.0% +/- 14.6% vs. 38.9%
      +/- 16.9%, difference = 13.9%; 95% CI = 5.7% to 22.0%). CONCLUSIONS: In this
      model of excised deep partial-thickness burns, a triple-antibiotic ointment
      enhanced reepithelialization and reduced scar depth and contraction compared with
      a silver-based foam dressing. This triple-antibiotic ointment should be
      considered as a control for studies evaluating novel topical burn therapies.

PMID- 26202793
TI  - Phase I studies: the role of publicly funded academic-healthcare partnerships.

PMID- 26202794
TI  - A randomised controlled trial comparing opt-in and opt-out home visits for
      tracing lost participants in a prospective birth cohort study.
AB  - BACKGROUND: Attrition is an important problem in cohort studies. Tracing cohort
      members who have moved or otherwise lost contact with the study is vital. There
      is some debate about the acceptability and relative effectiveness of opt-in
      versus opt-out methods of contacting cohort members to re-engage them in this
      context. We conducted a randomised controlled trial to compare the two approaches
      in terms of effectiveness (tracing to confirm address and consenting to continue
      in the study), cost-effectiveness and acceptability. METHODS: Participants in
      this trial were individuals (young people and mothers) recruited to the Avon
      Longitudinal Study of Parents and Children (ALSPAC), who had not engaged with the
      study in the previous 5 years and for whom mail had been returned from their last
      known address. The sampling frame was restricted to those for whom database
      searching led to a potential new address being found in the Bristol area. 300
      participants were randomly selected and assigned using stratified randomisation
      to the opt-in or opt-out arm. A tailored letter was sent to the potential new
      address, either asking participants to opt in to a home visit, or giving them the
      option to opt out of a home visit. Fieldworkers from Ipsos MORI conducted home
      visits to confirm address details. RESULTS: The proportion who were traced was
      higher in the opt-out arm (77/150 = 51 %) than the opt-in arm (6/150 = 4 %), as
      was the proportion who consented to continue in ALSPAC (46/150 = 31 % v 4/150 = 3
      %). The mean cost per participant was L8.14 in the opt-in arm and L71.93 in the
      opt-out arm. There was no evidence of a difference in acceptability between the
      opt-in and opt-out approaches. CONCLUSION: Since the opt-in approach yielded very
      low response rates, and there were no differences in terms of acceptability, we
      conclude that the opt-out approach is the most effective method of tracing
      disengaged study members. The gains made in contacting participants must be
      weighed against the increase in cost using this methodology.

PMID- 26202795
TI  - Role of Fractional-Flow Reserve in Guiding Percutaneous Revascularization in
      Stable Coronary Artery Disease.
AB  - Optimal medical therapy unarguably forms the cornerstone of management for
      patients with stable coronary artery disease. There is, however, a significant
      body of evidence suggesting that reduction of ischemia can be achieved more
      effectively with revascularization than medical therapy and can confer
      significant symptomatic and prognostic advantages. Nonetheless, owing to
      limitations of coronary angiography and conventional non-invasive functional
      testing for myocardial ischemia, targeting of hemodynamically significant
      coronary stenoses for revascularization is often difficult. We discuss the role
      of invasive fractional-flow reserve evaluation in guiding percutaneous
      revascularization procedures for patients with stable coronary artery disease and
      its potential impact on outcomes for these patients. 

PMID- 26202796
TI  - Gelucire-Based Nanoparticles for Curcumin Targeting to Oral Mucosa: Preparation,
      Characterization, and Antimicrobial Activity Assessment.
AB  - The purpose of the study was to prepare and characterize curcumin (Cur) solid
      lipid nanoparticles (CurSLN) with a high-loading capacity and chemical stability
      for the treatment of oral mucosal infection. CurSLN were formulated using
      different lipids, namely, Gelucire 39/01, Gelucire 50/13, Precirol, Compritol,
      and poloxamer 407 as a surfactant. Formulae were evaluated for their entrapment
      efficiency, particle size, and ex vivo mucoadhesion test. Microbiological
      evaluation was carried out on six microorganisms, five of which are the most
      commonly affecting oral cavity in terms of determination of minimum inhibitory
      concentration (MIC), and minimum bactericidal concentration. Transmission
      electron microscopy was conducted for ultrathin section for Candida albicans
      treated with formulated Cur. The results showed high entrapment efficiency and
      stability enhancement for Cur powder. Significant amount of Cur was retained onto
      the mucosal tissue indicating preferential mucosal uptake. CurSLN showed higher
      antimicrobial activity as compared with Cur raw material and chemically
      stabilized Cur where it showed MIC (0.185, 0.09375, 0.75, 3, 1.5, and 0.1875
      mg/mL) against Staphylococcus aureus, Streptococcus mutans, Viridansstrept,
      Escherichia coli, Lactobacillus acidophilus, and Candida albicans, respectively.
      The prepared lipid nanoparticles maintained Cur chemical stability and
      microbiological activity. The lack of local antimicrobial therapeutics with
      minimum side effects augments the importance of studying natural products for
      this purpose.

PMID- 26202797
TI  - Subclinical Thyroid Dysfunction and Depressive Symptoms among the Elderly: A
      Prospective Cohort Study.
AB  - BACKGROUND: Subclinical hypothyroidism has been associated with depressive
      symptoms in cross-sectional studies, but prospective data and data on subclinical
      hyperthyroidism are scarce. METHODS: In the Leiden substudy of the Prospective
      Study of Pravastatin in the Elderly at Risk (PROSPER), thyroid-stimulating
      hormone and free T4 levels were measured at baseline and repeated after 6 months
      in adults aged 70-82 years with preexisting cardiovascular disease or known
      cardiovascular risk factors to define persistent thyroid functional status. Main
      outcome measures were depressive symptoms, assessed with the Geriatric Depression
      Scale 15 (GDS-15) at baseline and after 3 years. All analyses were adjusted for
      age, gender and education. RESULTS: In 606 participants (41% women; mean age 75
      years) without antidepressant medication, GDS-15 scores at baseline did not
      differ for participants with subclinical hypothyroidism (n = 47; GDS-15 score
      1.75, 95% CI 1.29-2.20, p = 0.53) or subclinical hyperthyroidism (n = 13; GDS-15
      score 1.64, 95% CI 0.78-2.51, p = 0.96) compared to euthyroid participants (n =
      546; mean GDS-15 score 1.60, 95% CI 1.46-1.73). After 3 years, compared to the
      euthyroid participants, changes in GDS-15 scores did not differ for participants
      with subclinical hypothyroidism (x0394;GDS-15 score -0.03, 95% CI -0.50 to 0.44,
      p = 0.83), while subclinical hyperthyroidism was associated with an increase in
      GDS scores (x0394;GDS-15 score 1.13, 95% CI 0.32-1.93, p = 0.04). All results
      were similar for persistent subclinical thyroid dysfunction. CONCLUSIONS: In this
      largest prospective study on the association of persistent subclinical thyroid
      dysfunction and depression, subclinical hypothyroidism was not associated with
      increased depressive symptoms among older adults at high cardiovascular risk.
      Persistent subclinical hyperthyroidism might be associated with increased
      depressive symptoms, which requires confirmation in a larger prospective study.

PMID- 26202798
TI  - Identification of Drosophila Mutants Affecting Defense to an Entomopathogenic
      Fungus.
AB  - Fungi cause the majority of insect disease. However, to date attempts to model
      host-fungal interactions with Drosophila have focused on opportunistic human
      pathogens. Here, we performed a screen of 2,613 mutant Drosophila lines to
      identify host genes affecting susceptibility to the natural insect pathogen
      Metarhizium anisopliae (Ma549). Overall, 241 (9.22%) mutant lines had altered
      resistance to Ma549. Life spans ranged from 3.0 to 6.2 days, with females being
      more susceptible than males in all lines. Speed of kill correlated with within
      host growth and onset of sporulation, but total spore production is decoupled
      from host genotypes. Results showed that mutations affected the ability of
      Drosophila to restrain rather than tolerate infections and suggested trade-offs
      between antifungal and antibacterial genes affecting cuticle and gut structural
      barriers. Approximately, 13% of mutations where in genes previously associated
      with host pathogen interactions. These encoded fast-acting immune responses
      including coagulation, phagocytosis, encapsulation and melanization but not the
      slow-response induction of anti-fungal peptides. The non-immune genes impact a
      wide variety of biological functions, including behavioral traits. Many have
      human orthologs already implicated in human disorders; while others were
      mutations in protein and non-protein coding genes for which disease resistance
      was the first biological annotation. 

PMID- 26202800
TI  - Open defecation is associated with raised risk of preterm birth among Indian
      women.

PMID- 26202799
TI  - Chest pain syndromes are associated with high rates of recidivism and costs in
      young United States Veterans.
AB  - BACKGROUND: Recurrent chest pain is common in patients with and without coronary
      artery disease. The prevalence and burden of these symptoms on healthcare is
      unknown. OBJECTIVES: To compare chest pain return visits (recidivism) in patients
      with unexplained chest pain (UCP) against reference group of patients with
      coronary artery disease (CAD) and estimate the annual cost of recurrent chest
      pain. METHODS: In a retrospective cohort study, a Veteran Affairs (VA)
      administrative and clinical database of Veterans who were deployed to or served
      in support of the wars in Iraq or Afghanistan was queried for first disease
      specific ICD-9 code to form two cohorts (UCP or CAD). Patients were followed
      between 09/2001-09/2010 for the first and cumulative return visits for UCP or
      cardiac pain (ACS or angina) to clinic, emergency department or admission; or for
      all-cause death. Time to return was analyzed using Cox regression and negative
      binomial models and adjusted for age, gender, race, marital status, and risk
      factors (hypertension, hyperlipidemia, diabetes, smoking and obesity). Direct
      total costs included inpatient, outpatient and fee basis (non-VA) costs. RESULTS:
      Of 749,036 patients, 20,521 had UCP and 5303 had CAD. UCP patients were young and
      had a lower burden of risk factors than CAD cohort (p < .01). Yet, these patients
      were likely to return earlier with any chest pain (adjusted Hazard Ratio [aHR] =
      1.76; 95 % CI 1.65-1.88); or unexplained chest pain than CAD patients (aHR: 1.89;
      95 % CI 1.77-2.01). UCP patients were also likely to return more frequently for
      any chest pain (aRate Ratio = 1.54; 95 % CI 1.43-1.64) or UCP than CAD patients
      (aRR =2.63; 95 % CI 2.43-2.87). Per 100 patients, the 1-year cumulative returns
      were 37 visits for reference group and 45 visits for UCP cohort. The annual costs
      for chest pain averaged $69,009 for CAD and $57,336 for UCP patients (log
      geometric mean ratio=1.25; 95 % CI 1.18-1.32). CONCLUSION: Chest pain recidivism
      is common and costly even in patients without known CAD. We need evidence-based
      guidelines for these patients to minimize returns.

PMID- 26202801
TI  - Long-Term Effects of the Life Skills Program IPSY on Substance Use: Results of a
      4.5-Year Longitudinal Study.
AB  - This study investigated the long-term effectiveness of a Life Skills program with
      regard to use and proneness to legal and illicit drug use across a 4.5-year study
      interval. The universal school-based Life Skills program IPSY (Information +
      Psychosocial Competence = Protection) against adolescent substance use was
      implemented over 3 years (basic program in grade 5 and booster sessions in grades
      6 and 7). Over the same time period, it was evaluated based on a longitudinal
      quasi-experimental design with intervention and control group, including two
      follow-up assessments after program completion [six measurement points; N (T1) =
      1657 German students; M age (T1) = 10.5 years]. Applying an HLM approach, results
      showed that participation in IPSY had a significant effect on the frequency of
      smoking, and proneness to illicit drug use, across the entire study period. In
      addition, shorter-term effects were found for the frequency of alcohol use in
      that intervention effects were evident until the end of program implementation
      but diminished 2 years later. Thus, IPSY can be deemed an effective intervention
      against tobacco use and proneness to and use of illicit drugs during adolescence;
      however, further booster sessions may be necessary in later adolescence to
      enhance youths' resistance skills when alcohol use becomes highly normative among
      peers.

PMID- 26202802
TI  - Gray and white matter imaging: A biomarker for cognitive impairment in early
      Parkinson's disease?
AB  - BACKGROUND: The aim of this work was to investigate the cortical and white matter
      changes that underlie cognitive impairment in patients with incident Parkinson's
      disease (PD) disease using voxel-based morphometry and diffusion tensor imaging.
      METHODS: Newly diagnosed nondemented PD (n = 125) and control subjects (n = 50)
      were recruited from the Incidence of Cognitive Impairment in Cohorts with
      Longitudinal Evaluation in Parkinson's Disease Study and completed cognitive
      assessments and 3T structural and diffusion tensor MR imaging. Voxel-based
      morphometry was performed to investigate the relationship between gray matter
      volume and cognitive ability. Microstructural white matter changes were assessed
      with diffusion tensor imaging measures of fractional anisotropy and mean
      diffusivity using tract-based spatial statistics. RESULTS: Increased mean
      diffusivity was observed bilaterally in subjects with PD, relative to controls (P
      = 0.019). Increased mean diffusivity was associated with performance on the
      semantic fluency and Tower of London tasks in frontal and parietal white matter
      tracts, including the cingulum, superior longitudinal fasciculus, inferior
      longitudinal fasciculus, and inferior fronto-occipital fasciculus. There was no
      difference in total gray matter volume between groups; however, bilateral
      reductions in frontal and parietal gray matter volume were associated with
      reduced performance on measures of executive function in PD subjects.
      CONCLUSIONS: At the earliest stages of PD, regionally specific increases in
      central white matter mean diffusivity are present and suggest early axonal
      damage. Such changes are not accompanied by significant gray matter volume loss
      and are consistent with proposed models of pathological progression of the
      disease. Structural MRI, especially diffusion tensor imaging analysis, offers
      potential as a noninvasive biomarker reflecting cognitive impairment in PD.

PMID- 26202803
TI  - High-Density 2D Homo- and Hetero- Plasmonic Dimers with Universal Sub-10-nm Gaps.
AB  - Fabrication of high-density plasmonic dimers on a large (wafer) scale is crucial
      for applications in surface-enhanced spectroscopy, bio- and molecular sensing,
      and optoelectronics. Here, we present an experimental approach based on
      nanoimprint lithography and shadow evaporation that allows for the fabrication of
      high-density, large-scale homo- (Au-Au and Ag-Ag) and hetero- (Au-Ag) dimer
      substrates with precise and consistent sub-10-nm gaps. We performed scanning
      electron, scanning transmission electron, and atomic force microscopy studies
      along with a complete electron energy-loss spectroscopy (EELS) characterization.
      We observed distinct plasmonic modes on these dimers, which are well interpreted
      by finite-difference time-domain (FDTD) and plasmon hybridization calculations. 

PMID- 26202804
TI  - Meta-analysis of the human leukocyte antigen-G (HLA-G) 14 bp insertion/deletion
      polymorphism as a risk factor for preeclampsia.
AB  - The non-classical major histocompatibility complex, human leukocyte antigen (HLA)
      G, plays an important role in pregnancy. HLA-G mediates proper interaction
      between maternal immune cells and fetal trophoblasts invading the uterine wall,
      to ensure successful placental development and function. Several HLA-G gene
      variants have been shown to be associated with development of preeclampsia (PE),
      but the reported associations of the HLA-G 14 base pair (bp) insertion/deletion
      (I/D) polymorphism (rs66554220) with PE are inconsistent. In this meta-analysis
      of HLA-G 14 bp I/D in each member of the family triad, we estimated risk (odds
      ratio [OR], 95% confidence interval) of associations with PE based on nine
      published offspring, nine mother and three father case-control studies. No
      significant increased risk associations between PE and HLA-G 14 bp I/D were
      detected in any of the family triad members (offspring: OR = 1.08-1.21, P = 0.57
      0.74; mothers: OR = 1.11-1.28, P = 0.07-0.44; fathers: OR = 1.09-1.65, P = 0.07
      0.70). Of the 20 comparisons performed, 14 (70%) were non-heterogeneous and seven
      of these had zero heterogeneity (I(2) = 0%). Sensitivity treatment confirmed
      robustness for the overall lack of association for HLA-G 14 bp I/D. In subgroup
      analysis, significant association between HLA-G 14 bp I/D and PE was shown in
      offspring from primipara (OR = 1.66-1.95, P = 0.04) and European Caucasian
      pregnancies (OR = 1.37-2.03, P = 0.02-0.03). However, heterogeneity and
      sensitivity tests suggest that further investigation is needed to determine if
      HLA-G 14 bp I/D is involved in trophoblast HLA-G expression and PE development in
      these subgroups. 

PMID- 26202805
TI  - Tanshinone IIA attenuates cardiac dysfunction in endotoxin-induced septic mice
      via inhibition of NADPH oxidase 2-related signaling pathway.
AB  - Cardiac dysfunction is a critical event during sepsis/septic shock. Tanshinone
      IIA (TIIA), a compound extracted from herb medicine Danshen, has been shown
      possessing anti-inflammatory and anti-oxidative properties. It is possible,
      therefore, that treatment with TIIA may attenuate cardiac dysfunction during
      sepsis/septic shock through inhibition of inflammation. To test this possibility,
      we preadministrated C57BL/6 mice with TIIA prior to lipopolysaccharide (LPS)
      challenge. LPS significantly suppressed left ventricular function as evidenced by
      decreases in EF% and FS% in mice. However, TIIA pretreatment significantly
      attenuated cardiac dysfunction following LPS challenge. Furthermore, TIIA
      markedly attenuated the LPS-induced upregulation of circulating tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels. Meanwhile, LPS
      challenge significantly increased myocardial reactive oxygen species (ROS)
      production, which was attenuated by TIIA. Moreover, TIIA treatment dramatically
      decreased the level of the Nox2, reduced phosphorylation levels of extracellular
      signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase
      (p38 MAPK) expression. In conclusion, TIIA effectively improves cardiac function
      during endotoxemia in mice. This is attributed to TIIA reducing inflammatory
      cytokines release and inhibiting the Nox2 signaling during endotoxemia. 

PMID- 26202806
TI  - High-mobility group box-1-Toll-Like receptor 4 axis mediates the recruitment of
      endothelial progenitor cells in alkali-induced corneal neovascularization.
AB  - Endothelial progenitor cells (EPCs) promote both physiological and pathological
      neovascularization. Recently we found high-mobility group box-1 (HMGB1)-Toll-like
      receptor 4 (TLR4) signaling pathway promotes corneal neovascularization (CNV)
      induced by alkali in a mouse model. However, it is still unclear whether HMGB1
      TLR4 promotes the mobility of EPCs. In this study, we explored the role of HMGB1
      TLR4 signaling in EPC recruitment by modulating the activity of HMGB1-TLR4
      signaling in the corneas of alkali-induced CNV mouse model. The level of EPC
      recruitment in injured corneas, as detected by flow cytometry, is increased and
      reaches the peak level 4days after injury. Activating TLR4 with exogenous HMGB1
      or LPS enhances the EPC recruitment, whereas inhibiting the activity of HMGB1 and
      TLR4 with A-box (selective HMGB1 antagonist) or LPS-RS (selective TLR4
      antagonist), respectively, reverses this phenotype. Moreover, the TLR4 mediated
      EPC recruitment is associated with up-regulation of stromal cell-derived factor-1
      (SDF-1), a pivotal cytokine in EPC mobilization. Activation of TLR4 or HMGB1
      leads to increased SDF-1 expression, while blocking TLR4 or HMGB1 inhibits the
      expression of SDF-1. Topical administration of AMD-3100, an antagonist of SDF-1
      receptor, suppresses the TLR4-mediated EPC recruitment and ameliorates CNV. Our
      results indicated that activation of HMGB1-TLR4 signaling pathway promotes EPC
      recruitment in CNV, at least in part through up-regulation of SDF-1.

PMID- 26202807
TI  - Anti-inflammatory effects of Brazilian ginseng (Pfaffia paniculata) on TNBS
      induced intestinal inflammation: Experimental evidence.
AB  - Inflammatory bowel disease (IBD) is a chronic, relapsing, idiopathic inflammation
      of the gastrointestinal tract. Clinical studies suggest that the initiation of
      IBD is multifactorial, involving genetics, the immune system and environmental
      factors, such as diet, drugs and stress. Pfaffia paniculata is an adaptogenic
      medicinal plant used in Brazilian folk medicine as an "anti-stress" agent. Thus,
      we hypothesised that the P. paniculata enhances the response of animals subjected
      to colonic inflammation. Our aim was to investigate the intestinal anti
      inflammatory activity of P. paniculata in rats before or after induction of
      intestinal inflammation using trinitrobenzenesulfonic acid (TNBS). The animals
      were divided into groups that received the vehicle, prednisolone or P. paniculata
      extract daily starting 14 days before or 7 days after TNBS induction. At the end
      of the procedure, the animals were killed and their colons were assessed for the
      macroscopic damage score (MDS), extent of the lesion (EL) and weight/length
      ratio, myeloperoxidase (MPO) activity and glutathione (GSH), cytokines and C
      reactive protein (CRP) levels. Histological evaluation and ultrastructural
      analysis of the colonic samples were performed. Treatment with the 200mg/kg dose
      on the curative schedule was able to reduce the MDS and the EL. In addition, MPO
      activity was reduced, GSH levels were maintained, and the levels of pro
      inflammatory cytokines and CRP were decreased. In conclusion, the protective
      effect of P. paniculata was related to reduced oxidative stress and CRP colonic
      levels, and due to immunomodulatory activity as evidenced by reduced levels of IL
      1beta, INF-gamma, TNF-alpha and IL-6.

PMID- 26202808
TI  - Baicalein attenuates inflammatory responses by suppressing TLR4 mediated NF
      kappaB and MAPK signaling pathways in LPS-induced mastitis in mice.
AB  - Baicalein is a phenolic flavonoid presented in the dry roots of Scutellaria
      baicalensis Georgi. It has been reported that baicalein possesses a number of
      biological properties, such as antiviral, antioxidative, anti-inflammatory,
      antithrombotic, and anticancer properties. However, the effect of baicalein on
      mastitis has not yet been reported. This research aims to detect the effect of
      baicalein on lipopolysaccharide (LPS)-induced mastitis in mice and to investigate
      the molecular mechanisms. Baicalein was administered intraperitoneally 1h before
      and 12h after LPS treatment. The results indicated that baicalein treatment
      markedly attenuated the damage of the mammary gland induced by LPS, suppressed
      the activity of myeloperoxidase (MPO) and the levels of tumor necrosis factor
      (TNF-alpha) and interleukin (IL-1beta) in mice with LPS-induced mastitis.
      Besides, baicalein blocked the expression of Toll-like receptor 4 (TLR4) and then
      suppressed the phosphorylation of nuclear transcription factor-kappaB (NF-kappaB)
      p65 and degradation inhibitor of NF-kappaBalpha (IkappaBalpha) and, and inhibited
      the phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-jun
      NH2-terminal kinase (JNK) in mitogen-activated protein kinase (MAPK) signal
      pathway. These findings suggested that baicalein may have a potential prospect
      against mastitis. 

PMID- 26202809
TI  - Polymorphisms of OPG and their relation to the mineral density of bones in pre-
      and postmenopausal women.
AB  - OBJECTIVES: The aim of the study was to evaluate the frequency of gene
      polymorphisms OPG -163A/G, -950T/C and 1181G/C, assessing their relations with
      the clinical parameters of osseous turnover and the degree of postmenopausal
      osteoporosis. STUDY DESIGN: The study included 800 women of postmenopausal (505)
      and reproductive (295) age from Poland. The postmenopausal group included women
      with osteoporosis and osteopenia, as well as healthy individuals. All the women
      of reproductive age were healthy. The frequency of the tested gene polymorphisms
      was evaluated within the group where BMD (bone mineral density) was marked and
      also in the control group. MAIN OUTCOME MEASURES: The frequencies of the
      polymorphisms of OPG genotypes in the women were characteristic of the
      population. RESULTS: OPG -950T/C polymorphism has been associated with body
      weight and birth weight. OPG 1181G/C and OPG -163A/G polymorphisms have been
      associated not only with body weight and birth weight, but also with reduced bone
      density and an increased risk of postmenopausal osteoporosis. CONCLUSIONS:
      Evaluation of the polymorphism -950T/C of the OPG gene showed that the CC
      genotype may appear as an increased risk factor for the faster loss of bone mass
      and the onset of osteoporosis in Polish postmenopausal women. This polymorphism
      may be a genetic marker that is responsible for the development of osteoporosis.
      The homozygous genotypes of polymorphisms 1181G/C and -163A/G of the OPG gene may
      play a role in increased risks of osteoporosis and may be linked to the birth
      weights of women.

PMID- 26202810
TI  - Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth
      Factor-beta Signaling Pathway.
AB  - BACKGROUND: Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes
      oncogenic transformation. Tumor growth and metastasis require fibrotic and
      angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular
      tissue repair process. METHODS AND RESULTS: In wild-type mice, Sirt7 expression
      increased in response to acute cardiovascular injury, including myocardial
      infarction and hind-limb ischemia, particularly at the active wound healing site.
      Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7(-/-)) mice showed
      susceptibility to cardiac rupture after myocardial infarction, delayed blood flow
      recovery after hind-limb ischemia, and impaired wound healing after skin injury.
      Histological analysis showed reduced fibrosis, fibroblast differentiation, and
      inflammatory cell infiltration in the border zone of infarction in Sirt7(-/-)
      mice. In vitro, Sirt7(-/-) mouse-derived or Sirt7 siRNA-treated cardiac
      fibroblasts showed reduced transforming growth factor-beta signal activation and
      low expression levels of fibrosis-related genes compared with wild-type mice
      derived or control siRNA-treated cells. These changes were accompanied by
      reduction in transforming growth factor receptor I protein. Loss of Sirt7
      activated autophagy in cardiac fibroblasts. Transforming growth factor-beta
      receptor I downregulation induced by loss of Sirt7 was blocked by autophagy
      inhibitor, and interaction of Sirt7 with protein interacting with protein kinase
      Calpha was involved in this process. CONCLUSION: Sirt7 maintains transforming
      growth factor receptor I by modulating autophagy and is involved in the tissue
      repair process.

PMID- 26202812
TI  - Effect of Folic Acid Supplementation on Renal Phenotype and Epigenotype in Early
      Weanling Intrauterine Growth Retarded Rats.
AB  - BACKGROUND/AIMS: The objective of this study was to examine the responses of p53
      promoter methylation involved in kidney structure and function of early weaning
      intrauterine growth retarded (IUGR) rats to dietary folic acid supplementation.
      METHOD: Sprague-Dawley rats were fed isocaloric diets containing either 21%
      protein diet (normal feed) or 10% protein diet throughout pregnancy and normal
      feed during lactation. After weaning, Offspring were then fed onto normal feed
      and normal feed supplemented with 5 mg folic acid / kg feed for a month, this
      produced 4 dietary groups (maternal diet/ weanling diet): Con, Folic, IUGR and
      IUGR+Folic. Renal function, renal structure, p53 promoter methylation and protein
      expression of offspring rats were measured at postnatal 2 months and 3 months.
      RESULTS: Glomerular volume, blood urea nitrogen, 24 hours urine protein were
      significantly elevated in IUGR rats compared with Con rats but were decreased by
      dietary folic acid supplementation. p53 protein expression in IUGR rats were
      significantly higher than that in Con rats, and p53 promoter methylation status
      in IUGR rats was reduced significantly compared with Con rats. However, the
      changes in p53 gene expression and DNA methylation status of IUGR rats were
      reversed by dietary folic acid supplementation. CONCLUSIONS: Our study showed for
      the first time that folic acid supplementation during early period of life could
      reverse the abnormality in renal p53 methylation status and protein expression,
      glomerular volume and renal function of IUGR rats offspring.

PMID- 26202811
TI  - Combination of the Immune Modulator Fingolimod With Alteplase in Acute Ischemic
      Stroke: A Pilot Trial.
AB  - BACKGROUND: Inflammatory and immune responses triggered by brain ischemia worsen
      clinical outcomes of stroke and contribute to hemorrhagic transformation, massive
      edema, and reperfusion injury associated with intravenous alteplase. We assessed
      whether a combination of the immune-modulator fingolimod and alteplase is safe
      and effective in attenuating reperfusion injury in patients with acute ischemic
      stroke treated within the first 4.5 hours of symptom onset. METHODS AND RESULTS:
      In this multicenter trial, we randomly assigned 25 eligible patients with
      hemispheric ischemic stroke stemming from anterior or middle cerebral arterial
      occlusion to receive alteplase alone and 22 patients to receive alteplase plus
      oral fingolimod 0.5 mg daily for 3 consecutive days within 4.5 hours of the onset
      of ischemic stroke. Compared with patients who received alteplase alone, patients
      who received the combination of fingolimod with alteplase exhibited lower
      circulating lymphocytes, smaller lesion volumes (10.1 versus 34.3 mL; P=0.04),
      less hemorrhage (1.2 versus 4.4 mL; P=0.01), and attenuated neurological deficits
      in National Institute of Health Stroke Scales (4 versus 2; P=0.02) at day 1.
      Furthermore, restrained lesion growth from day 1 to 7 (-2.3 versus 12.1 mL;
      P<0.01) with a better recovery at day 90 (modified Rankin Scale score 0-1, 73%
      versus 32%; P<0.01) was evident in patients given fingolimod and alteplase. No
      serious adverse events were recorded in all patients. CONCLUSIONS: In this pilot
      study, combination therapy of fingolimod and alteplase was well tolerated,
      attenuated reperfusion injury, and improved clinical outcomes in patients with
      acute ischemic stroke. These findings need to be tested in further clinical
      trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT02002390.

PMID- 26202813
TI  - Estimation of spatial distribution of heavy metals in groundwater using
      interpolation methods and multivariate statistical techniques; its suitability
      for drinking and irrigation purposes in the Middle Black Sea Region of Turkey.
AB  - Monitoring of heavy metal concentrations in groundwater potentially used for
      drinking and irrigation is very important. This study collected groundwater
      samples from 78 wells in July 2012 and analyzed them for 17 heavy metals (Pb, Zn,
      Cr, Mn, Fe, Cu, Cd, Co, Ni, Al, As, Mo, Se, B, Ti, V, Ba). Spatial distributions
      of these elements were identified using three different interpolation methods
      [inverse distance weighing (IDW), radial basis function (RBF), and ordinary
      kriging (OK)]. Root mean squared error (RMSE) and mean absolute error (MAE) for
      cross validation were used to select the best interpolation methods for each
      parameter. Multivariate statistical analysis [cluster analysis (CA) and factor
      analysis (FA)] were used to identify similarities among sampling sites and the
      contribution of variables to groundwater pollution. Fe and Mn levels exceeded
      World Health Organization (WHO) recommended limits for drinking water in almost
      all of the study area, and some locations had Fe and Mn levels that exceeded Food
      and Agriculture Organization (FAO) guidelines for drip irrigation systems. Al,
      As, and Cd levels also exceeded WHO guidelines for drinking water. Cluster
      analysis classified groundwater in the study area into three groups, and factor
      analysis identified five factors that explained 73.39% of the total variation in
      groundwater, which are as follows: factor 1: Se, Ti, Cr, Mo; factor 2: Ni, Mn,
      Co, Ba; factor 3: Pb, Cd; factor 4: B, V, Fe, Cu; and factor 5: AS, Zn. As a
      result of this study, it could be said that interpolation methods and
      multivariate statistical techniques gave very useful results for the
      determination of the source.

PMID- 26202814
TI  - Spatiotemporal changes of land use patterns in high mountain areas of Northeast
      Turkey: a case study in Macka.
AB  - High mountain forests (HMFs) have an important significance in forest ecosystems,
      but the benefits from such ecosystems have been compromised in recent years. In
      Turkey, HMFs constitute significant portions of Turkish forests because they
      cover 4% of Turkey; 15% of all Turkish forest areas are HMFs. The Eastern Black
      Sea region has a particular importance for HMFs due to its biological diversity
      and the rich presence of endemic species. This study analyzes the changes in
      spatial and temporal patterns of forest cover in HMF from 1973 to 2008 in the
      town of Macka, which is located at the center of the Eastern Black Sea region of
      Turkey. The spatial and temporal change patterns of land use are quantified by
      interpreting spatial data. Remote sensing (RS), geographical information system
      (GIS), and a spatial pattern analysis program for categorical maps (FRAGSTATS)
      have been used for data collection, analysis, and presentation. The results
      showed that the HMF areas had biphasic growth from 1973 to 2008. Despite a net
      increase of 200.6 ha in forested areas between 1984 and 2008, there was an
      overall decrease from 1973 to 2008. The annual percentage of forestation for the
      forest areas within the study period was 0.04% in Macka. The amount of aggregated
      forest area fragments rose from 388 in 1973 to 711 in 2008. The increase in the
      HMF of Macka can be explained to some extent by the change in the demographic
      structure of Macka and its plateaus, which contributed to changes in the daily
      life of the population of Macka and its villages, such as changes in annual
      incomes, their lifestyles, decrease in transhumance and stockbreeding, decrease
      in the time of dwelling on the plateaus, and changes in the traditional
      architectural style.

PMID- 26202815
TI  - Community composition, abundance and biomass of tintinnids (Ciliata: Protozoa) in
      the Western Harbour, south-eastern Mediterranean Sea, Egypt.
AB  - Seasonal variations in species composition, abundance and biomass of tintinnids
      (Protozoa: Ciliata) were investigated in the Western Harbour, seasonally during
      2012. There were remarkable seasonal variations in environmental parameters,
      phytoplankton concentrations and abundance and biomass of tintinnids: highest in
      spring and lowest in autumn. Annual average abundance and biomass of tintinnids
      were 8.435 ind. l(-1) and 3.725 MUg C l(-1), respectively. A total of 29 species
      of tintinnids belonging to 11 genera was identified. Of which, Tintinnopsis was
      the most abundant genus in terms of number of species (9), but Favella was the
      best quantitatively (89% of the total tintinnids). The overall mean abundance and
      biomass were highest (mean 24.415 ind. l(-1) and 10.355 MUg C l(-1),
      respectively) during spring than the remaining seasons. Due to significant
      positive relationship between the total biomass of tintinnids and phytoplankton
      concentrations, food supply is not a problem for tintinnids harbouring in the
      Western Harbour. Hence, predation loss by meso- and macrozooplankton might be the
      possible reasons for the estimated low biomass of tintinnids in the present
      study. Some of the seasonal environmental factors as water salinity, nitrite,
      dissolved oxygen and pH values exert an influence on the species composition,
      abundance and biomass of tintinnids.

PMID- 26202816
TI  - TMDL for phosphorus and contributing factors in subtropical watersheds of
      southern China.
AB  - Water eutrophication, particularly that caused by phosphorus runoff, is of major
      concern in China due to the serious threats it poses to watershed environments.
      We investigated one forested and nine agricultural watersheds with areas of 9
      5212 ha in a hilly region of Hunan Province in a subtropical region of southern
      China from 2010 to 2012 to study total phosphorus (TP) loads and contributing
      factors. The annual TP loads varied from 35.7 to 222.1 kg P km(-2) year(-1) among
      the different watersheds, with the rainy season of spring and summer accounting
      for 56.3-82.0% of TP loss. The highest total maximum daily load (TMDL, 0.5 kg P
      km(-2) day(-1)) and existing exported daily TP loads (DTPL, 1.8 kg P km(-2) day(
      1)) were observed under high flow and moist flow conditions in the ten
      watersheds. However, the target daily reduction ratios for the DTPLs to reach the
      water quality standard of 0.05 mg P L(-1) varied little with flow condition in
      the stream but depended on the type of watershed, i.e., <50, <80, and 80-90% for
      forested, agricultural, and livestock-dominated watersheds, respectively. Gray
      relational analysis (GRA) suggested that livestock density was the most important
      factor for watershed TP load under various hydrologic conditions, while livestock
      density (LD), soil available phosphorous (SAP), cropland percentage, and mean
      shape index (SHMN) were notable factors for daily reduction rate (DRR) under high
      and moist flow conditions. Therefore, to protect the local watershed
      environments, watershed management approaches that include the regulation of
      livestock production are recommended as the most effective means of reducing P
      loads at the watershed scale in subtropical areas of southern China.

PMID- 26202817
TI  - Advantages and Disadvantages of Different Implementation Strategies of Non
      Invasive Prenatal Testing in Down Syndrome Screening Programmes.
AB  - BACKGROUND: Implementation of non-invasive prenatal testing (NIPT) in Down
      syndrome screening programmes requires health policy decisions about its
      combination with other tests and its timing in pregnancy. AIM: Our aim was to aid
      health policy decision makers by conducting a quantitative analysis of different
      NIPT implementation strategies. METHODS: Decision trees were created to
      illustrate all plausible alternatives in a theoretical cohort of 100,000 pregnant
      women in five screening programmes: classical screening by the first-trimester
      combined test (FCT), pre-selection of high-risk women prior to NIPT by the FCT,
      NIPT as the first screening test at 10 weeks and at 13 weeks, and the
      simultaneous conductance of NIPT and the FCT. RESULTS: Pre-selection by FCT prior
      to NIPT reduces the number of amniocenteses to a minimum because of a reduction
      of false-positive NIPT results. If NIPT is the first screening test, it detects
      almost all fetal Down syndrome cases. NIPT at 10 weeks reassures women early in
      pregnancy, while NIPT at 13 weeks prevents unnecessary tests due to spontaneous
      miscarriages and allows for immediate confirmation by amniocentesis. CONCLUSION:
      Every implementation strategy has its advantages and disadvantages. The most
      favourable implementation strategy may be NIPT as the first screening test at 13
      weeks, offering the most accurate screening test for Down syndrome, when the risk
      for spontaneous miscarriage has declined remarkably and timely confirmation by
      amniocentesis can be performed.

PMID- 26202818
TI  - Bacterial endotoxin and non-alcoholic fatty liver disease in the general
      population: a prospective cohort study.
AB  - BACKGROUND: Patients with non-alcoholic steatohepatitis (NASH) have increased
      intestinal permeability and small intestine bacterial overgrowth. AIMS: To test
      the hypothesis that endotoxemia is associated with non-alcoholic fatty liver
      disease (NAFLD) in the general population, and to study dietary factors
      associated with endotoxemia. METHODS: Nine hundred and twenty adults were
      randomly selected from the government's census database and underwent proton
      magnetic resonance spectroscopy to assess hepatic steatosis. Endotoxemia was
      assessed using the limulus amebocyte lysate, lipopolysaccharide-binding protein
      (LBP) and EndoCab immunoglobulin G (IgG) assays. RESULTS: Two hundred and sixty
      three (29%) subjects had NAFLD. Subjects with NAFLD had slightly higher LBP (P <
      0.001) and EndoCab IgG (P = 0.013) levels. EndoCab IgG remained an independent
      factor associated with intrahepatic triglycerides after adjusting for other
      metabolic factors. Among 565 subjects without NAFLD at baseline who had repeated
      assessment at a median interval of 47 months, 78 (13.8%) developed incident NAFLD
      and they also had higher LBP (P = 0.016). Moreover, LBP was associated with
      insulin resistance and dyslipidaemia, and modestly increased with the cytokeratin
      18 fragment level but not liver stiffness measurement by transient elastography.
      Although total energy consumption and individual macronutrients were not
      associated with endotoxemia, current drinkers (mostly <140 g/week) had lower
      endotoxin, EndoCab IgG and fetuin-A levels than nondrinkers. CONCLUSIONS:
      Endotoxin markers are associated with NAFLD in the general population, but do not
      have a major effect on NASH and fibrosis. People with modest alcohol consumption
      have lower serum endotoxin. This may partly explain the lower risk of NAFLD and
      NASH in modest drinkers in previous observational studies.

PMID- 26202819
TI  - Early (1-year) Discontinuation of Different Anti-osteoporosis Medications
      Compared: A Population-Based Cohort Study.
AB  - Although a number of reports suggest very low persistence with oral
      bisphosphonates, there is limited data on persistence with other anti
      osteoporosis medications. We compare rates of early discontinuation (in the first
      year) with all available outpatient anti-osteoporosis drugs in Catalonia, Spain.
      We conducted a population-based retrospective cohort study using data from the
      SIDIAP database. SIDIAP contains computerized primary care records and pharmacy
      dispensing data for >80 % of the population of Catalonia (>5 million people). All
      SIDIAP participants starting an anti-osteoporosis drug between 1/1/2007 and
      30/06/2011 (with 2 years wash-out) were included. We modelled persistence as the
      time between first prescription and therapy discontinuation (refill gap of at
      least 6 months) using Fine and Gray survival models with competing risk for
      death. We identified 127,722 patients who started any anti-osteoporosis drug in
      the study period. The most commonly prescribed drug was weekly alendronate (N =
      55,399). 1-Year persistence ranges from 40 % with monthly risedronate to 7.7 %
      with daily risedronate, and discontinuation was very common [from 49.5 % (monthly
      risedronate) to 84.4 % (daily risedronate)] as was also switching in the first
      year of therapy [from 2.8 % (weekly alendronate) to 10 % (daily alendronate)].
      Multivariable-adjusted models showed that only monthly risedronate had better one
      year persistence than weekly alendronate and teriparatide equivalent, whilst all
      other therapies had worse persistence. Early discontinuation with available anti
      osteoporosis oral drugs is very common. Monthly risedronate, weekly alendronate,
      and daily teriparatide are the drugs with the best persistence, whilst daily oral
      drugs have 40-60 % higher first-year discontinuation rates compared to weekly
      alendronate.

PMID- 26202820
TI  - Culturally appropriate health education for Type 2 diabetes in ethnic minority
      groups: an updated Cochrane Review of randomized controlled trials.
AB  - AIMS: To give an updated perspective of interventions from additional data
      collected since our first review, conducted in 2008. BACKGROUND: This updated
      Cochrane Review incorporates new information from recent randomized controlled
      trials on culturally appropriate diabetes health education interventions.
      METHODS: An electronic literature search of six databases was repeated, with
      databases of ongoing trials checked and three journals hand-searched. Meta
      analysis was carried out for sufficiently homogeneous outcomes, and common themes
      among trials were highlighted. RESULTS: A total of 22 new trials were added to
      the original 11. Meta-analysis of 28 trials containing suitable data showed
      significant improvements in glycaemic control (HbA1c ) and diabetes knowledge
      over a period of 24 months, after the delivery of culturally appropriate
      education to participants, compared with those receiving 'conventional' care.
      There were no consistent benefits over the control group in other selected
      outcome measures, and lack of data continued to make analysis of several outcome
      measures difficult. CONCLUSIONS: Research activity in this field has increased
      considerably over the past 6 years, with culturally appropriate diabetes
      education showing consistent benefits over conventional care in terms of
      glycaemic control and diabetes knowledge, sustained in the short- to mid-term.
      Further research is needed to determine the clinical significance of these
      improvements and their cost-effectiveness.

PMID- 26202822
TI  - Mood and food at the University of Turku in Finland: nutritional correlates of
      perceived stress are most pronounced among overweight students.
AB  - OBJECTIVES: We examined perceived stress and food intake at University of Turku,
      Finland. METHODS: This study was conducted as an online survey (1189 students).
      We computed two composite food intake pattern scores (sweets, cakes and snacks;
      fruits and vegetables), a dietary guideline adherence index, and the subjective
      importance of healthy eating. We assessed the correlations between perceived
      stress, and two food intake pattern scores, dietary guideline adherence index and
      subjective importance of healthy eating. We tested the associations between
      stress and the same variables, controlling for potential confounders for the
      whole sample, by gender, and by Body Mass Index (BMI). RESULTS: Fruits and
      vegetables intake and dietary guideline adherence were both negatively associated
      with stress. These negative associations were more pronounced in overweight and
      less pronounced in underweight compared to healthy weight students. Sweets,
      cookies and snacks consumption were not associated with stress. Stress was
      associated with lower subjective importance of healthy eating, independent of
      gender and BMI. CONCLUSIONS: Perceived stress might have relationships of
      different magnitudes in overweight vs. normal BMI or underweight persons. BMI
      could be an effect modifier of the stress-food habits association.

PMID- 26202823
TI  - Theoretical analysis of hot electron dynamics in nanorods.
AB  - Localised surface plasmons create a non-equilibrium high-energy electron gas in
      nanostructures that can be injected into other media in energy harvesting
      applications. Here, we derive the rate of this localised-surface-plasmon mediated
      generation of hot electrons in nanorods and the rate of injecting them into other
      media by considering quantum mechanical motion of the electron gas. Specifically,
      we use the single-electron wave function of a particle in a cylindrical potential
      well and the electric field enhancement factor of an elongated ellipsoid to
      derive the energy distribution of electrons after plasmon excitation. We compare
      the performance of nanorods with equivolume nanoparticles of other shapes such as
      nanospheres and nanopallets and report that nanorods exhibit significantly better
      performance over a broad spectrum. We present a comprehensive theoretical
      analysis of how different parameters contribute to efficiency of hot-electron
      harvesting in nanorods and reveal that increasing the aspect ratio can increase
      the hot-electron generation and injection, but the volume shows an inverse
      dependency when efficiency per unit volume is considered. Further, the electron
      thermalisation time shows much less influence on the injection rate. Our
      derivations and results provide the much needed theoretical insight for
      optimization of hot-electron harvesting process in highly adaptable metallic
      nanorods. 

PMID- 26202824
TI  - Semi-supervised Learning for the BioNLP Gene Regulation Network.
AB  - BACKGROUND: The BioNLP Gene Regulation Task has attracted a diverse collection of
      submissions showcasing state-of-the-art systems. However, a principal challenge
      remains in obtaining a significant amount of recall. We argue that this is an
      important quality for Information Extraction tasks in this field. We propose a
      semi-supervised framework, leveraging a large corpus of unannotated data
      available to us. In this framework, the annotated data is used to find plausible
      candidates for positive data points, which are included in the machine learning
      process. As this is a method principally designed for gaining recall, we further
      explore additional methods to improve precision on top of this. These are:
      weighted regularisation in the SVM framework, and filtering out unlabelled
      examples based on a probabilistic rule-finding method. The latter method also
      allows us to add candidates for negatives from unlabelled data, a method not
      viable in the unfiltered approach. RESULTS: We replicate one of the original
      participant systems, and modify it to incorporate our methods. This allows us to
      test the extent of our proposed methods by applying them to the GRN task data. We
      find a considerable improvement in recall compared to the baseline system. We
      also investigate the evaluation metrics and find several mechanisms explaining a
      bias towards precision. Furthermore, these findings uncover an intricate
      precision-recall interaction, depriving recall of its habitual immediacy seen in
      traditional machine learning set-ups. CONCLUSION: Our contributions are twofold.

PMID- 26202825
TI  - Acute Kidney Injury Facilitates Hypocalcemia by Exacerbating the
      Hyperphosphatemic Effect of Muscle Damage in Rhabdomyolysis.
AB  - BACKGROUND/AIMS: Hypocalcemia is an important complication of rhabdomyolysis for
      which several pathogenic factors, including acute kidney injury (AKI), have been
      proposed. To gain insight regarding the hypocalcemic roles of AKI in
      rhabdomyolysis, we retrospectively examined patients with rhabdomyolysis.
      METHODS: Of 28,387 patients admitted to the Department of Internal Medicine, 51
      patients met the inclusion criteria for the study. Serum calcium was analyzed
      based on laboratory data including indicators of AKI, serum creatine kinase (CK)
      and serum inorganic phosphate (iP). RESULTS: Twenty-two patients (43%) had
      hypocalcemia. Compared with patients without hypocalcemia, they had a higher
      prevalence of AKI (82 vs. 55%; p = 0.046), higher levels of peak CK (39,100 +/-
      50,600 vs. 9,800 +/- 11,900 IU/l; p = 0.003) and higher levels of peak iP (1.77
      +/- 1.10 vs. 1.10 +/- 0.35 mmol/l; p = 0.007). Indicators of AKI were correlated
      with peak CK and peak iP and were not significant variables in the regression
      analysis for hypocalcemia. Peak CK and peak iP were not correlated with each
      other. Impaired phosphate use by muscle contributed to the increased iP.
      CONCLUSION: These findings indicate that muscle damage is the primary
      hypocalcemic factor in rhabdomyolysis. AKI facilitated hypocalcemia by
      exacerbating the hyperphosphatemic effects of muscle damage. Aggressive
      hydration, which could increase oxygen supply and subsequently repair phosphate
      use in muscle, might reduce the incidence of hypocalcemia in rhabdomyolysis.

PMID- 26202826
TI  - Lack of protein kinase C-delta (PKCdelta) disrupts fertilization and embryonic
      development.
AB  - This study tested the function of protein kinase C delta (PKCdelta) during
      fertilization and embryonic development using gene-knockout (Prkcd(-/-)) mice.
      Fertility analysis revealed that Prkcd(-/-) mating pairs produce significantly
      fewer pups per litter than wild-type pairs (P < 0.05), and exhibit a high
      incidence of embryonic loss post-implantation. Both Prkcd(-/-) male as well as
      Prkcd(-/-) female mice mated to Prkcd(+/+) controls also showed reduced litter
      sizes, with a selective loss of Prkcd-null pups. Further analysis of the females
      demonstrated comparable in vitro fertilization outcomes between control and
      Prkcd(-/-) oocytes fertilized with wild-type sperm. Pregnant Prkcd(-/-) females,
      however, exhibited a reduced number of total implantations, suggesting a possible
      disruption in early embryo quality and/or implantation. In turn, male gamete
      analysis revealed that Prkcd(-/-) sperm demonstrated a decreased capacity to
      penetrate the zona pellucida (P < 0.05), necessary for successful fertilization.
      Moreover, we identified phosphorylated PKCdelta as a component of the sperm
      acrosome, indicating a potential role for this kinase in acrosome exocytosis.
      Therefore, loss of PKCdelta disrupts key reproductive functions in both males and
      females that limit fertility.

PMID- 26202827
TI  - Real time macrophage migration analysis and associated pro-inflammatory cytokine
      release on transparent carbon nanotube/polymer composite nano-film.
AB  - Surface chemistry and nanoscale surface morphology are both influential factors
      for cell adhesion, growth, and differentiation. In particular, cell migration is
      one of the major markers of initial immune response activation to implanted
      biomaterials. Despite their indication, it has been difficult to directly examine
      macrophages on nanoscale materials, because most nanomaterials possess greater
      thicknesses than nanoscale. This study developed transparent films comprising a
      carbon nanotube and polymer composite with controlled surface stiffness and
      nanoscale roughness. As nanoscale surface topography can incite immune cell
      activation, analysis of the real-time cell migration (including velocity) of
      macrophages due to changes in nanoscale surface topography of a biopolymer can
      support the direct relationship between initial macrophage dynamics and
      corresponding pro-inflammatory responses. Through real-time analysis, we have
      identified that surface chemistry and surface nanoscale topography are both
      independent factors mediating macrophage interactions, and, thus, immune cell
      behavior can be further controlled by the systematic variation of nanoscale
      surface topography for a given surface chemistry. Considering that the initial
      immune response can determine the fate and lifetime of implanted biomaterials,
      this study presents the direct relationship between initial macrophage dynamics
      and subsequent inflammatory cytokine release on transparent carbon nanotube
      polymer composites. 

PMID- 26202829
TI  - Nutraceuticals for Serum Lipid and Blood Pressure Control in Hypertensive and
      Hypercholesterolemic Subjects at Low Cardiovascular Risk.
AB  - INTRODUCTION: Primary cardiovascular (CV) prevention may be achieved by
      lifestyle/nutrition changes, although a relevant role is now emerging for
      specific, functional foods and nutraceutical compounds (NCs). The aim of this
      study was to investigate the efficacy and safety of NCs in lowering blood
      pressure (BP) and improving lipid profile, when added to diet and lifestyle
      management versus diet alone in a group of patients with hypertension (HT) and
      hypercholesterolemia (HCh) with low CV risk. METHODS: Sixty-six patients with HT
      and HCh with grade 1 essential HT (mean age 56.0 +/- 4.6 years) without history
      of CV diseases or organ damage were analyzed. These subjects were started on one
      tablet of an NC-containing red yeast rice, policosanol, berberine, folic acid and
      coenzyme Q10 once daily for 6 months and were age and gender matched with
      subjects following a diet program. Differences in clinic BP, 24-h ambulatory BP
      (24 h-ABPM), serum total cholesterol, low-density and high-density lipoprotein
      cholesterol (LDL-C and HDL-C) and triglyceride values were compared by analysis
      of variance. RESULTS: In the treatment group, a significant reduction of systolic
      24 h-ABPM (141.6 +/- 6.4 vs. 136.2 +/- 4.8 mmHg; p < 0.05) and pulse pressure 24
      h-ABPM (52.6 +/- 7.2 vs. 47.3 +/- 5.4 mmHg; p < 0.05) was found at the end of
      follow-up. A reduction of total cholesterol (-19.2%), LDL-C (-17.4%) and
      triglycerides (-16.3%) was observed (p < 0.001 for all); HDL-C remained
      unchanged. No difference was found in the control group. CONCLUSIONS: The tested
      NCs was found to be safe, well tolerated and effective in reducing mean 24-h
      systolic and 24-h pulse pressure and in improving lipid pattern.

PMID- 26202828
TI  - Critical Appraisal on Orbital Decompression for Thyroid Eye Disease: A Systematic
      Review and Literature Search.
AB  - INTRODUCTION: Orbital decompression is the indicated procedure for addressing
      exophthalmos and compressive optic neuropathy in thyroid eye disease. There are
      an abundance of techniques for removal of orbital bone, fat, or a combination
      published in the scientific literature. The relative efficacy and complications
      of these interventions in relation to the specific indications remain as yet
      undocumented. We performed a systematic review of the current published evidence
      for the effectiveness of orbital decompression, possible complications, and
      impact on quality of life. METHODS: We searched the current databases for medical
      literature and controlled trials, oculoplastic textbooks, and conference
      proceedings to identify relevant data up to February 2015. We included randomized
      controlled trials (RCTs) comparing two or more interventions for orbital
      decompression. RESULTS: We identified only two eligible RCTs for inclusion in the
      review. As a result of the significant variability between studies on
      decompression, i.e., methodology and outcome measures, we did not perform a meta
      analysis. One study suggests that the transantral approach and endonasal
      technique had similar effects in reducing exophthalmos but the latter is safer.
      The second study provides evidence that intravenous steroids may be superior to
      primary surgical decompression in the management of compressive optic neuropathy
      requiring less secondary surgical procedures. CONCLUSION: Most of the published
      literature on orbital decompression consists of retrospective, uncontrolled
      trials. There is evidence from those studies that removal of the medial and
      lateral wall (balanced) and the deep lateral wall decompression, with or without
      fat removal, may be the most effective surgical methods with only few
      complications. There is a clear unmet need for controlled trials evaluating the
      different techniques for orbital decompression. Ideally, future studies should
      address the effectiveness, possible complications, quality of life, and cost of
      each intervention.

PMID- 26202830
TI  - Synthesis of new asymmetric substituted boron amidines - reactions with CO and
      transfer hydrogenations of phenylacetylene.
AB  - The syntheses of the new asymmetric substituted boron amidines [N'-(2,6
      diisopropylphenyl)-N
      (pentafluorophenyl)acetimidamide]bis(pentafluorophenyl)borate () and [N'-(2,6
      diisopropylphenyl)-N-(4-cyanophenyl)acetimidamide]bis(pentafluorophenyl)borate ()
      were achieved by reaction of one equivalent of HB(C6F5)2 and the respective
      amidines and . These adducts, bearing electron withdrawing groups, showed
      thermally induced H2 elimination forming the four-membered cyclic diazaborate
      derivatives and . These new species were characterized by spectroscopic methods.
      X-ray diffraction studies have been carried out on , and . To prevent undesired
      reactions at the nitrile group, one equivalent of B(C6F5)3 was added to yielding
      the -B(C6F5)3 nitrile adduct . Compound underwent thermally induced
      dehydrogenation to give the four-membered cyclic diazaborate derivative . CO was
      inserted into the ring systems of and forming the five-membered diazaborolone
      derivatives and . Phenylacetylene reacted stoichiometrically with the asymmetric
      substituted boron amidines , and to give styrene by double H transfer. 

PMID- 26202832
TI  - Histopathology of hepatitis C in children, a systematic review: implications for
      treatment.
AB  - Chronic hepatitis C in children is usually considered a clinically mild and
      slowly progressive disease. Few pediatric studies focused on histopathology of
      children with hepatitis C are available. Those available show, overall, a wide
      spectrum of findings ranging from normal liver to cirrhosis and hepatocellular
      carcinoma. The present systematic review provides a comprehensive overview of the
      studies that explored histopathology in children with hepatitis C. Factors
      affecting the presence and the degree of necroinflammation, fibrosis and
      steatosis and the risk of progression to advanced liver disease were extensively
      evaluated. Insights on the possible role of histopathology findings in the
      decision-making process of whether or not to treat children with hepatitis C are
      provided. 

PMID- 26202833
TI  - LCST and UCST in One: Double Thermoresponsive Behavior of Block Copolymers of
      Poly(ethylene glycol) and Poly(acrylamide-co-acrylonitrile).
AB  - The change in thermoresponsive behavior from a single phase transition of upper
      critical solution temperature (UCST)-type of an acrylamide-acrylonitrile
      copolymer (AAm-co-AN) to a double responsive behavior (LCST-UCST-type (LCST,
      lower critical solution temperature)) in water by the introduction of a
      poly(ethylene glycol) (PEG) block is highlighted in the present work. The polymer
      is synthesized in a simple way by free-radical polymerization of acrylamide and
      acrylonitrile using a poly(ethylene glycol) (PEG) macro-azoinitiator. The dual
      thermoresponsive behavior was observed in a wide range of concentrations
      repeatable for many cycles with very small hysteresis depending upon the ratio of
      AAm, AN and PEG. Static light scattering (SLS) and dynamic light scattering (DLS)
      together with turbidity photometry and transmission electron microscopy confirmed
      a unique phase transition behavior due to the temperature dependent change in the
      morphology from micelles to agglomerates. The low cytotoxicity and two-in-one
      thermoresponsive behavior makes the polymer promising for biomedical applications
      in the future. 

PMID- 26202831
TI  - Hypothesis-based weight-of-evidence evaluation and risk assessment for
      naphthalene carcinogenesis.
AB  - Inhalation of naphthalene causes olfactory epithelial nasal tumors in rats (but
      not in mice) and benign lung adenomas in mice (but not in rats). The limited
      available human data have not identified an association between naphthalene
      exposure and increased respiratory cancer risk. Assessing naphthalene's
      carcinogenicity in humans, therefore, depends entirely on experimental evidence
      from rodents. We evaluated the respiratory carcinogenicity of naphthalene in
      rodents, and its potential relevance to humans, using our Hypothesis-Based Weight
      of-Evidence (HBWoE) approach. We systematically and comparatively reviewed data
      relevant to key elements in the hypothesized modes of action (MoA) to determine
      which is best supported by the available data, allowing all of the data from each
      realm of investigation to inform interpretation of one another. Our analysis
      supports a mechanism that involves initial metabolism of naphthalene to the
      epoxide, followed by GSH depletion, cytotoxicity, chronic inflammation,
      regenerative hyperplasia, and tumor formation, with possible weak genotoxicity
      from downstream metabolites occurring only at high cytotoxic doses, strongly
      supporting a non-mutagenic threshold MoA in the rat nose. We also conducted a
      dose-response analysis, based on the likely MoA, which suggests that the rat
      nasal MoA is not relevant in human respiratory tissues at typical environmental
      exposures. Our analysis illustrates how a thorough WoE evaluation can be used to
      support a MoA, even when a mechanism of action cannot be fully elucidated. A non
      mutagenic threshold MoA for naphthalene-induced rat nasal tumors should be
      considered as a basis to determine human relevance and to guide regulatory and
      risk-management decisions. 

PMID- 26202834
TI  - Partial resistance to homologous challenge infections of the digenean Echinostoma
      caproni in ICR mice.
AB  - In the present paper, we analyse the effect of a primary infection of ICR mice
      with Echinostoma caproni (Trematoda: Echinostomatidae) on the generation of
      resistance against homologous challenge infections. In ICR mice, E. caproni
      induces chronic infections concomitantly with strong responses characterized by
      the development of T-helper 1 (Th1)-type local immune responses with elevated
      levels of local interferon-gamma (IFN-gamma) and inflammatory and antibody
      responses. Here, the effect of the response generated against a primary infection
      with E. caproni in the generation of resistance against subsequent homologous
      infections was analysed. For this purpose, ICR mice were challenged with
      metacercariae of E. caproni and the results obtained showed that primary
      infection induces partial resistance against subsequent homologous infections in
      ICR mice. This resistance was expressed as a reduced rate of infection, worm
      recovery and worm size, indicating that primary infection induces changes in the
      host, making a hostile environment for the development of the parasite. 

PMID- 26202835
TI  - Possible Signatures of Hominin Hybridization from the Early Holocene of Southwest
      China.
AB  - We have previously described hominin remains with numerous archaic traits from
      two localities (Maludong and Longlin Cave) in Southwest China dating to the
      Pleistocene-Holocene transition. If correct, this finding has important
      implications for understanding the late phases of human evolution. Alternative
      interpretations have suggested these fossils instead fit within the normal range
      of variation for early modern humans in East Asia. Here we test this proposition,
      consider the role of size-shape scaling, and more broadly assess the affinities
      of the Longlin 1 (LL1) cranium by comparing it to modern human and archaic
      hominin crania. The shape of LL1 is found to be highly unusual, but on balance
      shows strongest affinities to early modern humans, lacking obvious similarities
      to early East Asians specifically. We conclude that a scenario of hybridization
      with archaic hominins best explains the highly unusual morphology of LL1,
      possibly even occurring as late as the early Holocene. 

PMID- 26202836
TI  - Antithrombotic drugs and subarachnoid haemorrhage risk. A nationwide case-control
      study in Denmark.
AB  - The study objective was to investigate the relationship between use of
      antithrombotic drugs and subarachnoid haemorrhage (SAH). We identified patients
      discharged from Danish neurosurgery units with a first-ever SAH diagnosis in 2000
      to 2012 (n=5,834). For each case, we selected 40 age-, sex- and period-matched
      population controls. Conditional logistic regression models were used to estimate
      odds ratios (aOR), adjusted for comorbidity, education level, and income. Low
      dose aspirin (ASA) use for < 1 month was associated with an increased risk of SAH
      (aOR 1.75, 95 % confidence interval [CI] 1.28-2.40). This aOR decreased to 1.26
      (95 %CI: 0.98-1.63) with 2-3 months of ASA use, and approached unity with use for
      more than three months (1.11, 95 %CI 0.97-1.27). Analyses with first-time users
      confirmed this pattern, which was also observed for clopidogrel. ASA treatment
      for three or more years was associated with an aOR of SAH of 1.13 (95 %CI: 0.86
      1.49). Short-term use (< 1 month) of vitamin K-antagonists (VKA) yielded an aOR
      of 1.85 (95 %CI 0.97-3.51) which dropped after 3+ years to 1.24, 95 %CI: 0.86
      1.77. The risk of SAH was higher in subjects in dual antithrombotic treatment
      (aOR 2.08, 95 %CI: 1.26-3.44), and in triple antithrombotic treatment (aOR 5.74,
      95 %CI: 1.76-18.77). In conclusion, use of aspirin,clopidogrel and VKA were only
      associated with an increased risk of SAH in the first three months after starting
      treatment. Long-term aspirin use carried no reduced SAH risk. Results should be
      interpreted cautiously due to their observational nature. 

PMID- 26202837
TI  - Comprehensive screening of genes resistant to an anticancer drug in esophageal
      squamous cell carcinoma.
AB  - Drug resistance to chemotherapy is a major issue in esophageal cancer management.
      Drug resistance may be mediated by genetic changes in the tumor; therefore, the
      identification of gene mutations may lead to better therapeutic outcomes. We used
      a novel method involving transposons to screen and identify drug-resistant genes.
      Transposons are DNA sequences that move from one location on the gene to another.
      A modified piggyBac transposon was designed as an insertion mutagen, and a
      cytomegalovirus (CMV) promoter sequence was added to induce strong transcription.
      When the transposon is inserted to the upstream of a certain gene, the gene will
      be overexpressed while when intserted down or intragenically, it will be
      downregulated. After establishing a transposon-tagged cell library, we treated
      cell lines derived from esophageal squamous cell carcinomas (ESCC) [Tohoku
      esophagus (TE)] with cisplatin (CDDP). We performed splinkerette PCR and TOPO
      cloning on the resistant colonies. Bacterial colonies were sequenced, and next
      generation sequencing was used to identify the overexpressed/downregulated
      sequences as candidate genes for CDDP resistance. We established 4 cell lines of
      transposon-tagged cells, TE4, 5, 9 and 15. We treated the two relatively viable
      cell lines, TE4 and TE15, with CDDP. We identified 37 candidate genes from 8
      resistant colonies. Eight genes were overexpressed whilst 29 were downregulated.
      Among these genes was Janus kinase 2 (JAK2) that is implicated in the progression
      of myeloproliferative neoplasms. We identified 37 candidate genes responsible for
      CDDP resistance in the two cell lines derived from ESCC cells. The method is
      inexpensive, relatively simple, and capable of introducing activating and de
      activating mutations in the genome, allowing for drug-resistant genes to be
      identified. 

PMID- 26202838
TI  - The value of software that provides clinically relevant information on drug
      interactions.

PMID- 26202839
TI  - Erratum: Disparities in Social Support for Youths With Type 1 Diabetes. Clinical
      Diabetes 2015;33:62-69.
AB  - [This corrects the article on p. 62 in vol. 33, PMID: 25897185.]. 

PMID- 26202840
TI  - A robust and automatic method for human parasite egg recognition in microscopic
      images.
AB  - With the accelerated movement of population, human parasitoses become an
      increasingly serious public health's problem. Currently, detections of parasite
      eggs through microscopic images are still the golden standard for diagnoses.
      However, this conventional method relies heavily on the experiences of
      inspectors, thus giving rise to misdiagnoses and missed diagnoses occasionally.
      And, as the number of clinical specimens increases rapidly, manual identification
      seems impractical. Hence, a fully automatic method is in desperate need. In this
      paper, we propose a robust method to segment and recognize the parasite eggs.
      Their contours are extracted using phase coherence technology, and the support
      vector machine (SVM) method based on shape and texture features is employed to
      classification of parasite eggs. Our novel method was comparable to the
      traditional method. The overall recognition rate was up to 95%, and the overall
      robustness indexes, including si, fnvf, fvpf, tpvf, were 95.7, 4.9, 3.7, 95.1,
      respectively, suggesting that our method is effective and the robustness is good,
      which has great potential to become a diagnostic method in the parasitological
      clinic.

PMID- 26202841
TI  - First molecular characterization of Sarcocystis tenella in Tatra chamois
      (Rupicapra rupicapra tatrica) in Poland.
AB  - In this study, sarcocysts from three Polish Tatra chamois were isolated and
      identified using morphological and molecular methods for the first time. Six
      cysts were found in the latissimus dorsi muscle and another two in the diaphragm.
      No sarcocysts were detected in the myocardium, tongue, and esophagus. The
      isolated cysts were long with rounded ends, 0.35-0.61 mm in length, and 0.02-0.06
      mm in width. All the sarcocysts were identified as Sarcocystis tenella on the
      basis of light microscopy and sequencing of cytochrome C oxidase subunit I (cox1)
      and small-subunit rRNA (ssu rRNA) genes. Comparative analysis showed a 99.23%
      identity of the cox1 gene sequences from Tatra chamois and sheep sarcocysts, and
      an even higher degree of sequence identity (99.88%) was documented in the case of
      the ssu rRNA gene. When compared at a haplotype level, all the sheep sequences of
      cox1 differed from those isolated from Tatra chamois. In contrast, one out of the
      two ssu rRNA haplotypes from the sheep isolates was identical with the haplotype
      from Tatra chamois. In conclusion, we showed that cox1 and ssu rRNA genes can be
      used as genetic markers for identification of the S. tenella, with cox1 gene
      providing better resolution during phylogenetic analyses. However, both genetic
      population analysis and phylogenetic inference with cox1 and ssu rRNA genes
      demonstrated that they do not constitute good markers for spatial differentiation
      of S. tenella.

PMID- 26202842
TI  - Disposition of firocoxib in late pregnant and early postpartum mares.
AB  - Pregnancy induces several physiologic changes that might impact the
      bioavailability, distribution, metabolism, and excretion of drugs. The objective
      of this study was to determine the effects of pregnancy on the disposition of
      oral firocoxib in mares. Seven pony mares received oral firocoxib paste at a dose
      of 0.1 mg/kg during late pregnancy and again 12 to 33 days postpartum. Firocoxib
      concentrations were measured in plasma by HPLC with ultraviolet detection.
      Maximum plasma concentrations were significantly lower in pregnant (50.0 +/- 21.8
      ng/mL) than in postpartum (73.7 +/- 25.6 ng/mL) mares. Plasma concentrations 24 h
      after administration, time to maximum plasma concentrations, and area under the
      plasma concentration versus time curve were not significantly different between
      late pregnancy and the postpartum period in mares.

PMID- 26202843
TI  - Infant Feeding and Timing of Complementary Foods in the Development of Type 1
      Diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction
      of the beta cells of the pancreas in genetically at-risk individuals. The
      autoimmune process that precedes the development of T1D is believed to be
      triggered by environmental factors, including nutrition. Early introduction of
      complementary foods has been implicated in the etiology of T1D as a possible
      explanation of the increasing incidence of the disease, particularly in children
      younger than 5 years of age. Infant feeding recommendations have been designed to
      promote adequate growth, provide essential nutrients, and reduce the risk of
      developing chronic illnesses. The World Health Organization and the American
      Academy of Pediatrics recommend exclusive breastfeeding to 6 months of age
      followed by continued breastfeeding as complementary foods are introduced. A lack
      of compliance with these recommendations has been observed in the general
      population as well as in infants at high risk for T1D. Dietary factors such as
      the provision of breast milk and duration of breastfeeding, the age at
      introduction of cow's milk and gluten-containing foods, as well as other
      complementary feeding have been investigated. However, the evidence that early
      infant feeding patterns are linked with T1D currently remains inconclusive. 

PMID- 26202844
TI  - The Role of Dietary Protein and Fat in Glycaemic Control in Type 1 Diabetes:
      Implications for Intensive Diabetes Management.
AB  - A primary focus of the management of type 1 diabetes has been on matching
      prandial insulin therapy with carbohydrate amount consumed. However, even with
      the introduction of more flexible intensive insulin regimes, people with type 1
      diabetes still struggle to achieve optimal glycaemic control. More recently,
      dietary fat and protein have been recognised as having a significant impact on
      postprandial blood glucose levels. Fat and protein independently increase the
      postprandial glucose excursions and together their effect is additive. This
      article reviews how the fat and protein in a meal impact the postprandial
      glycaemic response and discusses practical approaches to managing this in
      clinical practice. These insights have significant implications for patient
      education, mealtime insulin dose calculations and dosing strategies. 

PMID- 26202845
TI  - Structural Diversity of Class 1 Integrons in Multiresistant Strains of
      Escherichia coli Isolated from Patients in a Hospital in Mexico City.
AB  - Since a decade, Escherichia coli has been considered an important nosocomial
      pathogen due to the high number of isolates multiresistant to antimicrobials
      reported worldwide. In clinical and environmental strains, transposons, plasmids,
      and integrons are currently considered the principal genetic elements responsible
      for the acquisition of antibiotic resistance through horizontal transfer. The
      objective of this research was to correlate the resistance to antibiotics of E.
      coli clinical strains with the presence class I integrons. In the present study,
      one hundred E. coli strains were isolated and tested for susceptibility and
      resistance to antimicrobials. Class 1 integrons were detected by PCR, and the
      arrangement of gene cassettes was determined by sequencing. Twenty two strains
      were found to carry Class 1 integrons. Sequence analysis of the variable regions
      revealed the presence of several gene cassettes, such as dihydrofolate reductases
      (dfr2d, dfrA17, and dhfrXVb), adenylyl transferases (aadA2, addA5, and addA22),
      and chloramphenicol efflux pump (cmlA), and oxacillinase (bla OXA-1 ). The dfrA17
      addA5 arrangement prevailed upon other integrons in the study. This is the first
      report of the presence of the dfr2d and dhfrXVb-aadA2 cassette arrangements in a
      Class 1 integrons from clinical strains of E. coli. In most of the strains, it
      was found a direct relationship between genetic arrangements and resistance
      phenotypes. Four integrons were detected in plasmids that might be involved in
      the resistance genes transfer to other bacteria of clinical importance. Our
      results confirm the presence of Class 1 integrons and their essential role in the
      dissemination of resistance cassettes among E. coli strains.

PMID- 26202846
TI  - Endophytic Bacteria Isolated from Common Bean (Phaseolus vulgaris) Exhibiting
      High Variability Showed Antimicrobial Activity and Quorum Sensing Inhibition.
AB  - Endophytic bacteria play a key role in the biocontrol of phytopathogenic
      microorganisms. In this study, genotypic diversity was analyzed via repetitive
      element PCR (rep-PCR) of endophytic isolates of the phylum Actinobacteria that
      were previously collected from leaves of cultivars of common bean (Phaseolus
      vulgaris). Considerable variability was observed, which has not been reported
      previously for this phylum of endophytic bacteria of the common bean.
      Furthermore, the ethanol extracts from cultures of various isolates inhibited the
      growth of pathogenic bacteria in vitro, especially Gram-positive pathogens.
      Extracts from cultures of Microbacterium testaceum BAC1065 and BAC1093, which
      were both isolated from the 'Talisma' cultivar, strongly inhibited most of the
      pathogenic bacteria tested. Bean endophytic bacteria were also demonstrated to
      have the potential to inhibit the quorum sensing of Gram-negative bacteria. This
      mechanism may regulate the production of virulence factors in pathogens. The
      ability to inhibit quorum sensing has also not been reported previously for
      endophytic microorganisms of P. vulgaris. Furthermore, M. testaceum with capacity
      to inhibit quorum sensing appears to be widespread in common bean. The genomic
      profiles of M. testaceum were also analyzed via pulsed-field gel electrophoresis,
      and greater differentiation was observed using this method than rep-PCR; in
      general, no groups were formed based on the cultivar of origin. This study showed
      for the first time that endophytic bacteria from common bean plants exhibit high
      variability and may be useful for the development of strategies for the
      biological control of diseases in this important legume plant.

PMID- 26202847
TI  - Microbiology and initial antibiotic therapy for injection drug users and non
      injection drug users with cutaneous abscesses in the era of community-associated
      methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVES: The incidence of cutaneous abscesses has increased markedly since the
      emergence of community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA). Injection drug use is a risk factor for abscesses and may affect the
      microbiology and treatment of these infections. In a cohort of patients
      hospitalized with cutaneous abscesses in the era of CA-MRSA, the objectives were
      to compare the microbiology of abscesses between injection drug users and non
      injection drug users and evaluate antibiotic therapy started in the emergency
      department (ED) in relation to microbiologic findings and national guideline
      treatment recommendations. METHODS: This was a secondary analysis of two
      published retrospective cohorts of patients requiring hospitalization for acute
      bacterial skin infections between January 1, 2007, and May 31, 2012, in seven
      academic and community hospitals in Colorado. In the subgroup of patients with
      cutaneous abscesses, microbiologic findings and the antibiotic regimens started
      in the ED were compared between injection drug users and non-injection drug
      users. Antibiotic regimens involving multiple agents, lack of activity against
      MRSA, or an agent with broad Gram-negative activity were classified as discordant
      with Infectious Diseases Society of America (IDSA) guideline treatment
      recommendations. RESULTS: Of 323 patients with cutaneous abscesses, 104 (32%)
      occurred in injection drug users. Among the 235 cases where at least one
      microorganism was identified by culture, S. aureus was identified less commonly
      among injection drug users compared with non-injection drug users (55% vs. 75%, p
      = 0.003), with similar patterns observed for MRSA (33% vs. 47%, p = 0.054) and
      methicillin-susceptible S. aureus (17% vs. 26%, p = 0.11). In contrast to S.
      aureus, streptococcal species (53% vs. 25%, p < 0.001) and anaerobic organisms
      (29% vs. 10%, p < 0.001) were identified more commonly among injection drug
      users. Of 88 injection drug users and 186 non-injection drug users for whom
      antibiotics were started in the ED, the antibiotic regimens were discordant with
      IDSA guideline recommendations in 47 (53%) and 101 (54%), respectively (p =
      0.89). In cases where MRSA was ultimately identified, the antibiotic regimen
      started in the ED lacked activity against this pathogen in 14% of cases.
      CONCLUSIONS: Compared with non-injection drug users, cutaneous abscesses in
      injection drug users were less likely to involve S. aureus, including MRSA, and
      more likely to involve streptococci and anaerobes; however, MRSA was common in
      both groups. Antibiotic regimens started in the ED were discordant with national
      guidelines in over half of cases and often lacked activity against MRSA when this
      pathogen was present.

PMID- 26202848
TI  - Sleep disturbances predict prospective declines in resident physicians'
      psychological well-being.
AB  - BACKGROUND: Medical residency can be a time of increased psychological stress and
      sleep disturbance. We examine the prospective associations between self-reported
      sleep quality and resident wellness across a single training year. METHODS: Sixty
      nine (N=69) resident physicians completed the Brief Resident Wellness Profile
      (M=17.66, standard deviation [SD]=3.45, range: 0-17) and the Pittsburgh Sleep
      Quality Index (M=6.22, SD=2.86, range: 12-25) at multiple occasions in a single
      training year. We examined the 1-month lagged effect of sleep disturbances on
      residents' self-reported wellness. RESULTS: Accounting for residents' overall
      level of sleep disturbance across the entire study period, both the concurrent
      (within-person) within-occasion effect of sleep disturbance (B=-0.20, standard
      error [SE]=0.06, p=0.003, 95% confidence interval [CI]: -0.33, -0.07) and the
      lagged within-person effect of resident sleep disturbance (B=-0.15, SE=0.07,
      p=0.037, 95% CI: -0.29, -0.009) were significant predictors of decreased resident
      wellness. Increases in sleep disturbances are a leading indicator of resident
      wellness, predicting decreased well-being 1 month later. CONCLUSIONS: Sleep
      quality exerts a significant effect on self-reported resident wellness. Periodic
      evaluation of sleep quality may alert program leadership and the residents
      themselves to impending decreases in psychological well-being.

PMID- 26202849
TI  - Tumour necrosis factor receptor I blockade shows that TNF-dependent and TNF
      independent mechanisms synergise in TNF receptor associated periodic syndrome.
AB  - TNF receptor associated periodic syndrome (TRAPS) is an autoinflammatory disease
      involving recurrent episodes of fever and inflammation. It is associated with
      autosomal dominant mutations in TNF receptor superfamily 1A gene localised to
      exons encoding the ectodomain of the p55 TNF receptor, TNF receptor-1 (TNFR1).
      The aim of this study was to investigate the role of cell surface TNFR1 in TRAPS,
      and the contribution of TNF-dependent and TNF-independent mechanisms to the
      production of cytokines. HEK-293 and SK-HEP-1 cell lines were stably transfected
      with WT or TRAPS-associated variants of human TNF receptor superfamily 1A gene.
      An anti-TNFR1 single domain antibody (dAb), and an anti-TNFR1 mAb, bound to cell
      surface WT and variant TNFR1s. In HEK-293 cells transfected with death domain
      inactivated (R347A) TNFR1, and in SK-HEP-1 cells transfected with normal (full
      length) TNFR1, cytokine production stimulated in the absence of exogenous TNF by
      the presence of certain TNFR1 variants was not inhibited by the anti-TNFR1 dAb.
      In SK-Hep-1 cells, specific TRAPS mutations increased the level of cytokine
      response to TNF, compared to WT, and this augmented cytokine production was
      suppressed by the anti-TNFR1 dAb. Thus, TRAPS-associated variants of TNFR1
      enhance cytokine production by a TNF-independent mechanism and by sensitising
      cells to a TNF-dependent stimulation. The TNF-dependent mechanism requires cell
      surface expression of TNFR1, as this is blocked by TNFR1-specific dAb. 

PMID- 26202850
TI  - Polyacrylamide-based semi-interpenetrating networks for entrapment of laccase and
      their use in azo dye decolorization.
AB  - In this study, laccase from Trametes versicolor was immobilized in
      poly(acrylamide-crotonic acid)/sodium alginate [P(AAm-CrA)/alginate],
      poly(acrylamide-crotonic acid)/K-carrageenan [(P(AAm-CrA)/K-car)],
      poly(acrylamide-citraconic acid)/sodium alginate (P(AAm-CA)/alginate), and
      poly(acrylamide-citraconic acid)/K-carrageenan (P(AAm-CA)/K-car) semi
      interpenetrating network by entrapment method. Optimum pH and temperatures values
      were determined between 5.0-6.0 and 40-50  degrees C for free laccase (FL) and
      immobilized laccases, respectively. After 42 days of storage at 4  degrees C, FL
      and immobilized laccases retained their original activities in the range of 55%
      73%. Percent decolorization of Acid Orange 52 by free enyzme and enyzmes
      immobilized in hydrogels was found between 63% and 39%. Percent decolorization of
      Acid Orange 52 in the presence of mediator by free enyzme was found 73% and
      enyzmes immobilized in hydrogels were found as 73%.

PMID- 26202851
TI  - Linear, planar, and tubular molecular structures constructed by double planar
      tetracoordinate carbon D2hC2(BeH)4 species via hydrogen-bridged -BeH2Be- bonds.
AB  - This computational study identifies the rhombic D2hC2 (BeH)4 (2a) to be a species
      featuring double planar tetracoordinate carbons (ptCs). Aromaticity and the
      peripheral BeBeBeBe bonding around CC core contribute to the stabilization of the
      ptC structure. Although the ptC structure is not a global minimum, its high
      kinetic stability and its distinct feature of having a bonded C2 core from having
      two separated carbon atoms in the global minimum and other low-lying minima could
      make the ptC structure to be preferred if the carbon source is dominated by C2
      species. The electron deficiency of the BeH group allows the ptC species to serve
      as building blocks to construct large/nanostructures, such as linear chains,
      planar sheets, and tubes, via intermolecular hydrogen-bridged bonds (HBBs).
      Formation of one HBB bond releases more than 30.0 kcal/mol of energy, implying
      the highly exothermic formation processes and the possibility to synthesize these
      nano-size structures.

PMID- 26202852
TI  - Evidence-based (S3) Guideline on (anogenital) Lichen sclerosus.
AB  - Lichen sclerosus (LS) is an inflammatory skin disease that usually involves the
      anogenital area. All patients with symptoms or signs suspicious of lichen
      sclerosus should be seen at least once initially by a physician with a special
      interest in the disease in order to avoid delay in diagnosis, as early treatment
      may cure the disease in some and reduce or prevent scarring. The diagnosis is
      made clinically in most cases. Biopsies should only be performed under certain
      circumstances. The gold standard for treatment remains potent to very potent
      topical steroids; however, mild and moderate disease in boys and men may be cured
      by circumcision. Certain triggers should be avoided.
      http://www.euroderm.org/images/stories/guidelines/2014/S3-Guideline-on-Lichen
      sclerosus.pdf
      http://www.awmf.org/fachgesellschaften/mitgliedsgesellschaften/visitenkarte/fg/de
      tsche-gesellschaft-fuer-gynaekologie-und-geburtshilfe-dggg.html. 

PMID- 26202854
TI  - Hyperbaric oxygen therapy for acute coronary syndrome.
AB  - BACKGROUND: Acute coronary syndrome (ACS), includes acute myocardial infarction
      and unstable angina, is common and may prove fatal. Hyperbaric oxygen therapy
      (HBOT) will improve oxygen supply to the threatened heart and may reduce the
      volume of heart muscle that perishes. The addition of HBOT to standard treatment
      may reduce death rate and other major adverse outcomes.This an update of a review
      previously published in May 2004 and June 2010. OBJECTIVES: The aim of this
      review was to assess the evidence for the effects of adjunctive HBOT in the
      treatment of ACS. We compared treatment regimens including adjunctive HBOT
      against similar regimens excluding HBOT. Where regimens differed significantly
      between studies this is clearly stated and the implications discussed. All
      comparisons were made using an intention to treat analysis where this was
      possible. Efficacy was estimated from randomised trial comparisons but no attempt
      was made to evaluate the likely effectiveness that might be achieved in routine
      clinical practice. Specifically, we addressed:Does the adjunctive administration
      of HBOT to people with acute coronary syndrome (unstable angina or infarction)
      result in a reduction in the risk of death?Does the adjunctive administration of
      HBOT to people with acute coronary syndrome result in a reduction in the risk of
      major adverse cardiac events (MACE), that is: cardiac death, myocardial
      infarction, and target vessel revascularization by operative or percutaneous
      intervention?Is the administration of HBOT safe in both the short and long term?
      SEARCH METHODS: We updated the search of the following sources in September 2014,
      but found no additional relevant citations since the previous search in June 2010
      (CENTRAL), MEDLINE, EMBASE, CINAHL and DORCTHIM. Relevant journals were
      handsearched and researchers in the field contacted. We applied no language
      restrictions. SELECTION CRITERIA: Randomised studies comparing the effect on ACS
      of regimens that include HBOT with those that exclude HBOT. DATA COLLECTION AND
      ANALYSIS: Three authors independently evaluated the quality of trials using the
      guidelines of the Cochrane Handbook and extracted data from included trials.
      Binary outcomes were analysed using risk ratios (RR) and continuous outcomes
      using the mean difference (MD) and both are presented with 95% confidence
      intervals. We assessed the quality of the evidence using the GRADE approach. MAIN
      RESULTS: No new trials were located in our most recent search in September 2014.
      Six trials with 665 participants contributed to this review. These trials were
      small and subject to potential bias. Only two reported randomisation procedures
      in detail and in only one trial was allocation concealed. While only modest
      numbers of participants were lost to follow-up, in general there is little
      information on the longer-term outcome for participants. Patients with acute
      coronary syndrome allocated to HBOT were associated with a reduction in the risk
      of death by around 42% (RR: 0.58, (95% CI 0.36 to 0.92), 5 trials, 614
      participants; low quality evidence).In general, HBOT was well-tolerated. No
      patients were reported as suffering neurological oxygen toxicity and only a
      single patient was reported to have significant barotrauma to the tympanic
      membrane. One trial suggested a significant incidence of claustrophobia in single
      occupancy chambers of 15% (RR of claustrophobia with HBOT 31.6, 95% CI 1.92 to
      521). AUTHORS' CONCLUSIONS: For people with ACS, there is some evidence from
      small trials to suggest that HBOT is associated with a reduction in the risk of
      death, the volume of damaged muscle, the risk of MACE and time to relief from
      ischaemic pain. In view of the modest number of patients, methodological
      shortcomings and poor reporting, this result should be interpreted cautiously,
      and an appropriately powered trial of high methodological rigour is justified to
      define those patients (if any) who can be expected to derive most benefit from
      HBOT. The routine application of HBOT to these patients cannot be justified from
      this review.

PMID- 26202853
TI  - Error adjustments for file linking methods using encrypted unique client
      identifier (eUCI) with application to recently released prisoners who are HIV+.
AB  - Incarceration provides an opportunity to test for HIV, provide treatment such as
      highly active anti-retroviral therapy, as well as link infected persons to
      comprehensive HIV care upon their release. A key factor in assessing the success
      of a program that links released individuals to care is the time from release to
      receiving care in the community (linkage time). To estimate the linkage time,
      records from correction systems are linked to Ryan White Clinic data using
      encrypted Unique Client Identifier (eUCI). Most of the records that were linked
      using eUCI belong to the same individual; however, in some cases, it may link
      records incorrectly, or not identify records that should have been linked. We
      propose a Bayesian procedure that relies on the relationships between variables
      that appear in either of the data sources, as well as variables that exists in
      both to identify correctly linked records among all linked records. The procedure
      generates K datasets in which each pair of linked records is identified as a true
      link or a false link. The K datasets are analyzed independently, and the results
      are combined using Rubin's multiple imputation rules. A small validation dataset
      is used to examine different statistical models and to inform the prior
      distributions of the parameters. In comparison with previously proposed methods,
      the proposed method utilizes all of the available data and is both flexible and
      computationally efficient. In addition, this approach can be applied in other
      file linking applications.

PMID- 26202855
TI  - Methotrexate inhibits osteoclastogenesis by decreasing RANKL-induced calcium
      influx into osteoclast progenitors.
AB  - The increasing number of osteoporosis patients is a pressing issue worldwide.
      Osteoporosis frequently causes fragility fractures, limiting activities of daily
      life and increasing mortality. Many osteoporosis patients take numerous medicines
      due to other health issues; thus, it would be preferable if a single medicine
      could ameliorate osteoporosis and other conditions. Here, we screened 96 randomly
      selected drugs targeting various diseases for their ability to inhibit
      differentiation of osteoclasts, which play a pivotal role in development of
      osteoporosis, and identified methotrexate (MTX), as a potential inhibitor. MTX is
      currently used to treat sarcomas or leukemic malignancies or auto-inflammatory
      diseases such as rheumatoid arthritis (RA) through its anti-proliferative and
      immunosuppressive activities; however, a direct effect on osteoclast
      differentiation has not been shown. Here, we report that osteoclast formation and
      expression of osteoclastic genes such as NFATc1 and DC-STAMP, which are induced
      by the cytokine RANKL, are significantly inhibited by MTX. We found that RANKL
      dependent calcium (Ca) influx into osteoclast progenitors was significantly
      inhibited by MTX. RA patients often develop osteoporosis, and osteoclasts are
      reportedly required for joint destruction; thus, MTX treatment could have a
      beneficial effect on RA patients exhibiting high osteoclast activity by
      preventing both osteoporosis and joint destruction. 

PMID- 26202856
TI  - Effects of Fruit Extracts on Pancreatic Lipase Activity in Lipid Emulsions.
AB  - Pancreatic lipase is the most important enzyme in digestion of triglycerides.
      Reduction of energy intake from dietary fat through inhibition of this enzyme may
      be a strategy to prevent and treat obesity. In this study, the effect of 31 fruit
      extracts on pancreatic lipase was investigated using triolein, sunflower oil and
      rapeseed oil emulsions. Surprisingly, about 30 % of the fruits tested stimulated
      pancreatic lipase activity in oil emulsions by over 50 %. Only six fruit extracts
      were found to inhibit pancreatic lipase activity with the IC(50) value varying
      from 21.11 to 266.48 mg of fruit equivalent/ml of emulsion. Among them,
      chokeberry demonstrated the highest anti-lipase activity. The inhibitory activity
      ranks were comparable in all lipid emulsion models and suggest that consumption
      of chokeberry, red gooseberry and red currant fruits may be a new dietary option
      for reduction of fat absorption via inhibition of pancreatic lipase.

PMID- 26202858
TI  - Two universal physical principles shape the power-law statistics of real-world
      networks.
AB  - The study of complex networks has pursued an understanding of macroscopic
      behaviour by focusing on power-laws in microscopic observables. Here, we uncover
      two universal fundamental physical principles that are at the basis of complex
      network generation. These principles together predict the generic emergence of
      deviations from ideal power laws, which were previously discussed away by
      reference to the thermodynamic limit. Our approach proposes a paradigm shift in
      the physics of complex networks, toward the use of power-law deviations to infer
      meso-scale structure from macroscopic observations. 

PMID- 26202857
TI  - Long-term outcomes for newly-diagnosed multiple myeloma patients treated with
      pegylated liposomal doxorubicin and bortezomib: final results of CALGB (Alliance)
      10301, a multicentre phase II study.
AB  - Long-term outcomes and updated clinical efficacy and safety data were evaluated
      for newly-diagnosed multiple myeloma patients treated on a phase II study of
      bortezomib and pegylated liposomal doxorubicin (PegLD). Out of 61 patients, the
      overall response rate was 57% and the near-complete/complete response rate was
      7%. Patients aged >=65 years old had a higher incidence of treatment-related
      >=Grade 3 non-haematological toxicity (80% vs. 51%, P = 0.020). Median overall
      survival was 5.6 years and negatively impacted by the presence of International
      Staging System stage III disease, underscoring the need for novel treatment
      strategies for this group of patients.

PMID- 26202859
TI  - Past climate change and recent anthropogenic activities affect genetic structure
      and population demography of the greater long-tailed hamster in northern China.
AB  - The genetic diversity and the spatial structure of a species are likely
      consequences of both past and recent evolutionary processes, but relevant studies
      are still rare in East Asia where the Pleistocene climate has unique influences.
      In this study, we examined the impact of past climate change and recent
      anthropogenic activities on the genetic structure and population size of the
      greater long-tailed hamster (Tscherskia triton), an agricultural rodent pest
      species in northern China. DNA sequence data of 2 mitochondrial genes and
      genotypic data of 11 microsatellite DNA loci from 41 populations (545
      individuals) were gathered. Phylogenetic and population genetic analyses, as well
      as species distribution modeling and coalescent simulations, were conducted to
      infer its historical and demographic patterns and processes. Two deeply diverged
      mitochondrial clades were recovered. A small one was restricted to the Shandong
      Peninsula while the main clade was further divided into 3 geographic clusters by
      their microsatellite DNA genotypes: Northwest, North-center and Northeast.
      Divergence dating indicated a Middle-to-Late Pleistocene divergence between the 2
      clades. Demographic analysis indicated that all 3 and pooled populations showed
      consistent long-period expansions during last glacial period; but not during the
      Holocene, probably due to the impact of climate warming and human disturbances.
      Conflicting patterns between mtDNA and microsatellite markers imply an
      anthropogenic impact on North-center populations due to intensified agricultural
      cultivation in this region. Our study demonstrated that the impact of past
      glaciation on organisms in East Asia significantly differs from that of Europe
      and North America, and human activity is an important factor in determining the
      genetic diversity of a species, as well as its spatial structure. 

PMID- 26202860
TI  - Incorrect evaluation of the frequency of malnutrition and of its screening in
      hospitalized children by health care professionals.
AB  - RATIONALE, AIMS AND OBJECTIVES: Malnutrition screening is essential to detect and
      to treat patients with stunting or wasting. The aim was to evaluate the
      subjective perception of frequency and assessment of malnutrition by health care
      professionals. RESEARCH METHODS AND PROCEDURES: In a paediatric university
      hospital, a cross-sectional survey was conducted with a Likert scale approach to
      health care professionals and compared with objective measurements on a given day
      of frequency of malnutrition and of its screening. RESULTS: 279 health care
      professionals participated. The malnutrition rate, estimated versus measured, was
      16.8% and 34.8%, respectively. Conversely, the estimated frequency of
      malnutrition screening versus measured frequency was 80.6% versus 43.1%,
      respectively. Furthermore, the perception of health care professionals did not
      differ depending on their professional category or speciality. CONCLUSIONS: In
      conclusion, health care staff underestimates the prevalence of malnutrition in
      children by half and overestimates the frequency of appropriate screening
      practices for detection of malnutrition. This flawed/unreliable perception may
      disrupt both screening and the management of malnourished children. There is an
      urgent need to find out the reasons behind these errors caused by subjective
      perception in order to develop appropriate educational training to remedy the
      situation.

PMID- 26202861
TI  - Non-redox modulated fluorescence strategy for sensitive and selective ascorbic
      acid detection with highly photoluminescent nitrogen-doped carbon nanoparticles
      via solid-state synthesis.
AB  - Highly photoluminescent nitrogen-doped carbon nanoparticles (N-CNPs) were
      prepared by a simple and green route employing sodium alginate as a carbon source
      and tryptophan as both a nitrogen source and a functional monomer. The as
      synthesized N-CNPs exhibited excellent water solubility and biocompatibility with
      a fluorescence quantum yield of 47.9%. The fluorescence of the N-CNPs was
      intensively suppressed by the addition of ascorbic acid (AA). The mechanism of
      the fluorescence suppression of the N-CNPs was investigated, and the synergistic
      action of the inner filter effect (IFE) and the static quenching effect (SQE)
      contributed to the intensive fluorescence suppression, which was different from
      those reported for the traditional redox-based fluorescent probes. Owing to the
      spatial effect and hydrogen bond between the AA and the groups on the N-CNP
      surface, excellent sensitivity and selectivity for AA detecting was obtained in a
      wide linear relationship from 0.2 MUM to 150 MUM. The detection limit was as low
      as 50 nM (signal-to-noise ratio of 3). The proposed sensing systems also
      represented excellent sensitivity and selectivity for AA analysis in human
      biological fluids, providing a valuable platform for AA sensing in clinic
      diagnostic and drug screening. 

PMID- 26202863
TI  - HIV/AIDS prevalence in Israeli prisons: Is there a need for universal screening?
AB  - This study aimed to assess HIV/AIDS point-prevalence among inmates and evaluate
      costs related to universal screening as currently practiced and appraise its
      necessity. All inmates newly incarcerated in Israel (2003-2010) underwent HIV
      tests and their medical files were cross-matched the with the national HIV/AIDS
      registry to who had been newly infected and detected on prison entry. They were
      classified by key risk-groups. Of 108,866 new inmates during the period, 215 (0.2
      per cent) were diagnosed with HIV/AIDS, 44 of those (0.04 per cent) were not
      aware of their infection. A large majority (94.2 per cent) of the infected
      inmates were members of a key-risk group: drug-users, homosexuals, or originating
      from a high-HIV prevalence country. The direct cost of detecting a single HIV
      infected inmate who was not previously recorded was [euro ]12,386. The HIV/AIDS
      screening process can be improved by interviewing the new inmates and performing
      targeted HIV-testing for those who are members of a known risk-group. These data
      from Israel are pertinent to developed countries with low HIV prevalence, because
      they present a picture of all newly infected inmates over an 8-year period within
      the paradigm of a fully functional HIV surveillance system.

PMID- 26202864
TI  - Assessment of minimal residual disease in myeloma and the need for a consensus
      approach.
AB  - Treatment options for myeloma continue to develop at a rapid pace, and it is
      becoming increasingly challenging to determine the optimal therapeutic approaches
      because demonstrating a clear survival benefit now requires many years of follow
      up. The detection of minimal residual disease (MRD) is recognized as a sensitive
      and rapid approach to evaluate treatment efficacy that predicts progression-free
      and overall survival independent of categorical response assessment and patients'
      biology. The benefit of MRD analysis is reflected in the many different
      techniques (multiparameter flow cytometry, quantitative polymerase chain
      reaction, and high-throughput sequencing) and collaborative groups (including
      EMN, ESCCA, ICCS, EuroFlow, and EuroMRD) that have performed collaborative
      projects to harmonize quantitative MRD detection. The time has come to adopt a
      consensus approach, and this report reviews the benefits and disadvantages of
      different strategies for MRD detection in myeloma and highlights the requirements
      for a sensitive, reproducible, and clinically meaningful cellular analytical
      approach.

PMID- 26202865
TI  - Noncanonical sortase-mediated assembly of pilus type 2b in group B Streptococcus.
AB  - Group B Streptococcus (GBS) expresses 3 structurally distinct pilus types (1, 2a,
      and 2b) identified as important virulence factors and vaccine targets. These pili
      are heterotrimeric polymers, covalently assembled on the cell wall by sortase
      (Srt) enzymes. We investigated the pilus-2b biogenesis mechanism by using a
      multidisciplinary approach integrating genetic, biochemical, and structural
      studies to dissect the role of the 2 pilus-2b-associated Srts. We show that only
      1 sortase (SrtC1-2b) is responsible for pilus protein polymerization, whereas the
      second one (Srt2-2b) does not act as a pilin polymerase, but similarly to the
      housekeeping class A Srt (SrtA), it is involved in cell-wall pilus anchoring by
      targeting the minor ancillary subunit. Based on its function and sequence
      features, Srt2-2b does not belong to class C Srts (SrtCs), nor is it a canonical
      member of any other known family of Srts. We also report the crystal structure of
      SrtC1-2b at 1.9 A resolution. The overall fold resembles the typical structure of
      SrtCs except for the N-terminal lid region that appears in an open conformation
      displaced from the active site. Our findings reveal that GBS pilus type 2b
      biogenesis differs significantly from the current model of pilus assembly in gram
      positive pathogens.

PMID- 26202866
TI  - US Medicare, Medicaid, and nurse practitioners all turn 50.

PMID- 26202867
TI  - Isoniazid prevents Nrf2 translocation by inhibiting ERK1 phosphorylation and
      induces oxidative stress and apoptosis.
AB  - Isoniazid is used either alone or in combination with other drugs for the
      treatment of tuberculosis. It is also used for the prevention of tuberculosis.
      Chronic treatment of Isoniazid may cause severe liver damage leading to acute
      liver failure. The mechanism through which Isoniazid causes liver damage is
      investigated. Isoniazid treatment generates reactive oxygen species and induces
      apoptosis in Hep3B cells. It induces antioxidative and apoptotic genes leading to
      increase in mRNA expression and protein levels in Hep3B cells. Whole genome
      expression analysis of Hep3B cells treated with Isoniazid has resulted in
      differential expression of various genes playing prime role in regulation of
      apoptotic, antioxidative, DNA damage, cell signaling, cell proliferation and
      differentiation pathways. Isoniazid increased cytosolic Nrf2 protein level while
      decreased nuclear Nrf2 protein level. It also decreased ERK1 phosphorylation and
      treatment of Hep3B cells with ERK inhibitor followed by Isoniazid resulting in
      increased apoptosis in these cells. Two dimensional gel electrophoresis results
      have also shown differential expression of various protein species including heat
      shock proteins, proteins playing important role in oxidative stress, DNA damage,
      apoptosis, cell proliferation and differentiation. Results suggest that Isoniazid
      induces apoptosis through oxidative stress and also prevents Nrf2 translocation
      into the nucleus by reducing ERK1 phosphorylation thus preventing cytoprotective
      effect. 

PMID- 26202868
TI  - Glycation of bovine serum albumin by ascorbate in vitro: Possible contribution of
      the ascorbyl radical?
AB  - Ascorbic acid (AA) has been reported to be both pro-and antiglycating agent. In
      vitro, mainly proglycating effects of AA have been observed. We studied the
      glycation of bovine serum albumin (BSA) induced by AA in vitro. BSA glycation was
      accompanied by oxidative modifications, in agreement with the idea of
      glycoxidation. Glycation was inhibited by antioxidants including polyphenols and
      accelerated by 2,2'-azobis-2-methyl-propanimidamide and superoxide dismutase.
      Nitroxides, known to oxidize AA, did not inhibit BSA glycation. A good
      correlation was observed between the steady-state level of the ascorbyl radical
      in BSA samples incubated with AA and additives and the extent of glycation. On
      this basis we propose that ascorbyl radical, in addition to further products of
      AA oxidation, may initiate protein glycation. 

PMID- 26202869
TI  - Release of Cell-Free Ice Nucleators from Three Recombinant Ice Zymomonas mobilis
      Strains.
AB  - BACKGROUND/AIMS: This work is a study of the ability of three recombinant
      Zymomonas mobilis strains to release ice nucleators into their growth medium.
      METHODS: The recombinant ice(+)Z. mobilis cells were tested for their ability to
      produce cell-free ice nucleators, under three different growth temperatures and
      three different glucose concentrations. RESULTS: Cell-free ice nucleators were
      obtained from all the recombinant ice(+)Z. mobilis cells tested. The cell-free
      ice nucleation activity was not affected by the glucose concentration in the
      growth medium or the growth temperature. The freezing temperature threshold was
      below -7.6 degrees C, demonstrating a class C nucleating structure of the ice
      nucleation protein. The size of the ice nucleators was less than 0.22 MUm and
      their density was estimated as 1.024 +/- 0.004 g/ml by Percoll density
      centrifugation. The properties of the detected ice nucleators, in addition to the
      absence of pyruvate decarboxylase activity in the spent medium (a cytosolic
      marker), support that the cell-free ice nucleation activity was due to the
      extracellular release of ice nucleators. CONCLUSION: These findings indicate that
      the recombinant ice(+)Z. mobilis cells could be valuable for future use as a
      source of active cell-free ice nucleation protein.

PMID- 26202871
TI  - Secukinumab: a review in moderate to severe plaque psoriasis.
AB  - Secukinumab (CosentyxTM) is a fully human monoclonal immunoglobulin G1kappa
      antibody targeting human interleukin-17A, an important cytokine in the
      pathogenesis of psoriasis. Secukinumab, as well as being first in its drug class,
      is the first biologic treatment to be approved in the EU for the first-line
      systemic treatment of moderate to severe plaque psoriasis. This article reviews
      the pharmacologic properties of secukinumab and its clinical efficacy and
      tolerability in adult patients with moderate to severe plaque psoriasis. In
      clinical trials, subcutaneous secukinumab was more effective than placebo,
      etanercept and ustekinumab at improving both psoriasis symptoms (with high skin
      clearance) and health-related quality of life. Moreover, secukinumab was more
      effective than placebo in the difficult-to-treat palmoplantar and nail psoriasis
      populations. Secukinumab was generally well tolerated, with low immunogenicity.
      Longer-term, efficacy was sustained and secukinumab remained well tolerated.
      Subcutaneous secukinumab is an effective and generally well tolerated first-line
      treatment for moderate to severe plaque psoriasis, and is a useful addition to
      the treatment options for this disease. 

PMID- 26202872
TI  - Leaf metabolome in arbuscular mycorrhizal symbiosis.
AB  - Most land plants are associated with arbuscular mycorrhizal fungi, which colonise
      the plant roots and facilitate the uptake of water and nutrients. In turn, the
      fungi receive plant carbohydrates. Although the fungus is morphologically
      restricted to the roots, the exchange of substances and involvement of
      phytohormone signalling has consequences on systemic shoot tissues. Recent
      research provides growing insight in the species-specificity of leaf metabolic
      responses to arbuscular mycorrhiza, revealing that various metabolites can be
      affected. Such mycorrhiza-mediated changes in the chemical composition of leaf
      tissues can confer phytoprotection against different abiotic stresses. Moreover,
      they have consequences on numerous biotic interactions. In this review we
      highlight such findings and point out fields where more research is required. 

PMID- 26202870
TI  - Risk of colorectal cancer for people with a mutation in both a MUTYH and a DNA
      mismatch repair gene.
AB  - The base excision repair protein, MUTYH, functionally interacts with the DNA
      mismatch repair (MMR) system. As genetic testing moves from testing one gene at a
      time, to gene panel and whole exome next generation sequencing approaches,
      understandin g the risk associated with co-existence of germline mutations in
      these genes will be important for clinical interpretation and management. From
      the Colon Cancer Family Registry, we identified 10 carriers who had both a MUTYH
      mutation (6 with c.1187G>A p.(Gly396Asp), 3 with c.821G>A p.(Arg274Gln), and 1
      with c.536A>G p.(Tyr179Cys)) and a MMR gene mutation (3 in MLH1, 6 in MSH2, and 1
      in PMS2), 375 carriers of a single (monoallelic) MUTYH mutation alone, and 469
      carriers of a MMR gene mutation alone. Of the 10 carriers of both gene mutations,
      8 were diagnosed with colorectal cancer. Using a weighted cohort analysis, we
      estimated that risk of colorectal cancer for carriers of both a MUTYH and a MMR
      gene mutation was substantially higher than that for carriers of a MUTYH mutation
      alone [hazard ratio (HR) 21.5, 95% confidence interval (CI) 9.19-50.1; p <
      0.001], but not different from that for carriers of a MMR gene mutation alone (HR
      1.94, 95% CI 0.63-5.99; p = 0.25). Within the limited power of this study, there
      was no evidence that a monoallelic MUTYH gene mutation confers additional risk of
      colorectal cancer for carriers of a MMR gene mutation alone. Our finding suggests
      MUTYH mutation testing in MMR gene mutation carriers is not clinically
      informative.

PMID- 26202873
TI  - Multilayer and interconnected post-transcriptional and co-transcriptional control
      of plant NLRs.
AB  - During the last decades, a tremendous amount of progress has been made to better
      understand how plant NOD-like receptors (NLRs) are activated at the molecular
      level, post-translationally controlled, chaperoned and localized within the cell.
      Furthermore, several studies have demonstrated a functional role for alternative
      splicing (AS) in the regulation of NLR transcripts. However, our knowledge on the
      involvement of other post-transcriptional and co-transcriptional processes that
      regulate this class of immune receptors has remained, until recently, very
      limited. In the present review, we aim to provide an overview of recent findings
      highlighting the role and regulation of RNA silencing, non-sense mediated decay
      (NMD) and AS in the control of the abundance and composition of NLR transcripts
      during plant immunity. 

PMID- 26202874
TI  - A Study of a Geographical Cluster of Huntington's Disease in a Brazilian Town of
      Zona da Mata, Minas Gerais State.
AB  - BACKGROUND/AIMS: Our aim was to investigate a geographical cluster of
      Huntington's disease (HD) in Ervalia, a Brazilian town of Minas Gerais state
      (MG). Therefore, we calculated the minimum prevalence of HD in Ervalia, known to
      have many HD affected families. We also determined the genetic profile of the
      polymorphic CAG region of the HTT gene in 32 subjects of these affected families.
      METHODS: A descriptive cross-sectional study was performed, starting in January
      2011 until June 2013. Individuals who participated in the survey were all from
      Ervalia town, MG. RESULTS: The minimum prevalence rate found was 7.2/10,000
      people, higher than the worldwide prevalence. CONCLUSION: The minimum prevalence
      of HD in Ervalia was at least 10.3- to 14.4-fold greater than that of the world
      population, although it does not represent the overall prevalence of the disease
      in Brazil. Certainly an expanded survey in the country will lead to a lower
      prevalence estimate than Ervalia's.

PMID- 26202875
TI  - Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome,
      regardless of the age.
AB  - Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) of the
      elderly is defined as patients older than 50 years alone. However, recent studies
      showed young patients with sound immune status could also be affected. In this
      study, we investigated the clinical features and outcomes of patients with EBV
      positive DLBCL in the different age groups using different EBER cut-off values.
      The prevalence of EBV positive DLBCL was 14.0% (35/250) and 10.4% (26/250) for
      EBER cut-off of 20% and 50%, respectively. With both EBER cut-off values,
      patients with EBV DLBCL shared many unfavorable prognostic characteristics,
      regardless of age. EBV positive patients, both in the elderly and young groups,
      showed significantly worse overall survival and progression-free survival than
      negative cases. Moreover, no significant differences of outcomes were identified
      between different age groups with EBV positive DLBCL. In conclusion, EBV positive
      DLBCL patients, regardless of age, shared similar poor prognostic features and
      showed worse outcome than negative cases. We suggest that the age criterion of
      EBV positive DLBCL of the elderly, and possibly the name itself, be modified in
      future. 

PMID- 26202876
TI  - Laboratory and field methods for stable isotope analysis in human biology.
AB  - Stable isotope analysis (SIA; carbon, hydrogen, nitrogen, sulfur, and oxygen) of
      human tissues offers a means for assessing diet among living humans. Stable
      isotope ratios of broad categories of food and drink food vary systematically,
      and stable isotope ratios in consumer tissues represent a composite of the
      isotopic ratios of food and drink consumed during an individual's life. Isotopic
      evidence for diet is independent of errors in informant recall, and accrues
      during time periods when researchers are absent. Beyond diet reconstruction,
      tissue stable isotope ratios are sensitive to excursions from homeostasis, such
      as starvation and rapid growth. Because of their relationship to diet, geographic
      location, hydration, and nutritional status, stable isotope signatures in human
      tissues offer a window into human biocultural adaptations, past and present. This
      article describes methods for SIA that may be usefully applied in studies of
      living humans, with emphasis placed on carbon and nitrogen. Some of the
      ecological, physiological, and evolutionary applications of stable isotope data
      among living humans are discussed. By incorporating SIA in research, human
      biologists facilitate a productive dialog with bioarchaeologists, who routinely
      use stable isotope evidence, mingling different perspectives on human biology and
      behavior.

PMID- 26202877
TI  - Universal nature of collective plasmonic excitations in finite 1D carbon-based
      nanostructures.
AB  - We provide evidence of the plasmon resonances in a number of representative 1D
      finite carbon-based nanostructures using first-principle computational electronic
      spectroscopy studies. Our special purpose real-space/real-time all-electron time
      dependent density-functional theory simulator can perform excited-states
      calculations to obtain correct frequencies for known optical transitions, and
      capture various nanoscopic effects including collective plasmon excitations. The
      presence of 1D plasmons is universally predicted by the various numerical
      experiments, which also demonstrate a phenomenon of resonance splitting. For the
      metallic carbon nanotubes under study, the plasmons are expected to be related to
      the Tomonaga-Luttinger plasmons of infinitely long 1D structures. In-depth
      quantitative understanding of such resonances which have not been clearly
      identified in experiments so far, would be invaluable for future generations of
      nano-photonic and nano-electronic devices that employ 1D conductors. 

PMID- 26202878
TI  - Prognostic value of extracardiac incidental findings on attenuation correction
      cardiac computed tomography.
AB  - BACKGROUND: Attenuation corrected computed tomography (CTAC) is often performed
      to improve the specificity of single-photon emission tomography imaging.
      Extracardiac incidental findings are frequently observed. It is unclear whether
      these findings have any prognostic value. METHODS: Consecutive patients (n =
      1139) at a tertiary care center were retrospectively evaluated for incidental
      findings on CTAC. Clinically significant incidental findings were defined as
      findings warranting physician follow-up. Information regarding subsequent
      resource utilization was obtained by chart review. Cox proportional hazard model
      adjusted for demographic and clinical variables was used to evaluate association
      of these incidental findings with all-cause and cancer-specific mortality.
      RESULTS: A total of 135 (12%) patients with incidental findings were identified,
      83 of whom (68%) were newly diagnosed. Lung nodules were the most common finding,
      present in 92 (68%) patients. Over a median follow-up of 468 days, incidental
      findings were not significantly associated with increased risk of all-cause
      mortality (HR 1.34; 95% CI 0.77-2.33, P = 0.29) but was significantly associated
      with cancer-specific mortality (HR 3.21; 95% CI 1.26-8.14, P = 0.01). This
      association remained statistically significant when the analysis was limited to
      newly diagnosed incidental findings. Among patients with incidental findings,
      follow-up radiographic studies were conducted in 87%, and invasive procedures
      performed in 32%. Physician office-based follow-up of these findings occurred in
      42% of patients and incidental finding-related hospitalization occurred in 14%.
      CONCLUSIONS: This study shows that incidental findings are common and were
      associated with all-cause and cancer-specific mortality but only the later
      remained statistically significant after multivariable adjustment.

PMID- 26202879
TI  - Diboron complexes with bis-spiro structures as high-performance blue emitters for
      OLEDs.
AB  - To construct high-performance organoboron-based blue emitters for
      electroluminescent (EL) devices, two diboron complexes have been synthesized
      through the chelation of 2-(1-phenyl-1H-benzo[d]imidazole-2-yl)phenol or 2-(2
      pyridyl)phenol ligands with both boron atoms of the 9,10-diboraanthracene group.
      These complexes exhibit bright blue emissions in solution and in solid films with
      fluorescence quantum yields over 0.42, which benefit from their bis-spiro
      structures. In addition, they possess high thermal decomposition (>410  degrees
      C) and glass transition (>163  degrees C) temperatures. Moreover, they are
      excellent ambipolar transporting materials with high and balanced mobilities
      (>10(-4) cm(2) V(-1) s(-1)) for holes and electrons. Due to these excellent
      properties, the EL devices adopting these complexes as non-doped emitting layers
      emit blue light and exhibit low turn-on voltages (<3.2 V), high luminance (up to
      9041 cd m(-2)), as well as high current (up to 7.01 cd A(-1)) and power
      efficiencies (up to 7.58 lm W(-1)). To the best of our knowledge, these devices
      are so far the brightest and most efficient blue devices based on four-coordinate
      organoboron emitters. 

PMID- 26202881
TI  - Reduced peak, but no diurnal variation, in thrombin generation upon melatonin
      supplementation in tetraplegia. A randomised, placebo-controlled study.
AB  - Tetraplegic patients have increased risk of venous thrombosis despite anti
      thrombotic prophylaxis. Moreover, they have blunted plasma variations in
      melatonin and altered diurnal variation of several haemostatic markers, compared
      with able-bodied. However, whether healthy individuals and tetraplegic patients,
      with or without melatonin, display abnormalities in thrombin generation during a
      24-hour (h) cycle, is unknown. We therefore used the Calibrated Automated
      Thrombogram (CAT) assay to examine diurnal variations and the possible role of
      melatonin in thrombin generation. Six men with long-standing complete tetraplegia
      were included in a randomised placebo-controlled cross-over study with melatonin
      supplementation (2 mg, 4 consecutive nights), whereas six healthy, able-bodied
      men served as controls. Ten plasma samples were collected frequently during a 24
      h awake/sleep cycle. No significant diurnal variation of any of the measured CAT
      indices was detected in the three study groups. Whereas endogenous thrombin
      potential (ETP) was independent (p > 0.05) of whether the tetraplegic men
      received melatonin or placebo, melatonin decreased (p = 0.005) peak values in
      tetraplegia compared with those given placebo. Able-bodied men had lower (p =
      0.019) ETP and Lag-Time (p = 0.018) compared with tetraplegics receiving placebo.
      Neither the Time-to-Peak nor the Start-Tail was affected (p > 0.05) by melatonin
      in tetraplegia. In conclusion, indices of thrombin generation are not subjected
      to diurnal variation in healthy able-bodied or tetraplegia, but peak thrombin
      generation is reduced in tetraplegic men receiving oral melatonin. 

PMID- 26202880
TI  - Factors Governing P-Glycoprotein-Mediated Drug-Drug Interactions at the Blood
      Brain Barrier Measured with Positron Emission Tomography.
AB  - The adenosine triphosphate-binding cassette transporter P-glycoprotein
      (ABCB1/Abcb1a) restricts at the blood-brain barrier (BBB) brain distribution of
      many drugs. ABCB1 may be involved in drug-drug interactions (DDIs) at the BBB,
      which may lead to changes in brain distribution and central nervous system side
      effects of drugs. Positron emission tomography (PET) with the ABCB1 substrates
      (R)-[(11)C]verapamil and [(11)C]-N-desmethyl-loperamide and the ABCB1 inhibitor
      tariquidar has allowed direct comparison of ABCB1-mediated DDIs at the rodent and
      human BBB. In this work we evaluated different factors which could influence the
      magnitude of the interaction between tariquidar and (R)-[(11)C]verapamil or
      [(11)C]-N-desmethyl-loperamide at the BBB and thereby contribute to previously
      observed species differences between rodents and humans. We performed in vitro
      transport experiments with [(3)H]verapamil and [(3)H]-N-desmethyl-loperamide in
      ABCB1 and Abcb1a overexpressing cell lines. Moreover we conducted in vivo PET
      experiments and biodistribution studies with (R)-[(11)C]verapamil and [(11)C]-N
      desmethyl-loperamide in wild-type mice without and with tariquidar pretreatment
      and in homozygous Abcb1a/1b((-/-)) and heterozygous Abcb1a/1b((+/-)) mice. We
      found no differences for in vitro transport of [(3)H]verapamil and [(3)H]-N
      desmethyl-loperamide by ABCB1 and Abcb1a and its inhibition by tariquidar. [(3)H]
      N-Desmethyl-loperamide was transported with a 5 to 9 times higher transport ratio
      than [(3)H]verapamil in ABCB1- and Abcb1a-transfected cells. In vivo, brain
      radioactivity concentrations were lower for [(11)C]-N-desmethyl-loperamide than
      for (R)-[(11)C]verapamil. Both radiotracers showed tariquidar dose dependent
      increases in brain distribution with tariquidar half-maximum inhibitory
      concentrations (IC50) of 1052 nM (95% confidence interval CI: 930-1189) for (R)
      [(11)C]verapamil and 1329 nM (95% CI: 980-1801) for [(11)C]-N-desmethyl
      loperamide. In homozygous Abcb1a/1b((-/-)) mice brain radioactivity distribution
      was increased by 3.9- and 2.8-fold and in heterozygous Abcb1a/1b((+/-)) mice by
      1.5- and 1.1-fold, for (R)-[(11)C]verapamil and [(11)C]-N-desmethyl-loperamide,
      respectively, as compared with wild-type mice. For both radiotracers radiolabeled
      metabolites were detected in plasma and brain. When brain and plasma
      radioactivity concentrations were corrected for radiolabeled metabolites, brain
      distribution of (R)-[(11)C]verapamil and [(11)C]-N-desmethyl-loperamide was
      increased in tariquidar (15 mg/kg) treated animals by 14.1- and 18.3-fold,
      respectively, as compared with vehicle group. Isoflurane anesthesia altered
      [(11)C]-N-desmethyl-loperamide but not (R)-[(11)C]verapamil metabolism, and this
      had a direct effect on the magnitude of the increase in brain distribution
      following ABCB1 inhibition. Our data furthermore suggest that in the absence of
      ABCB1 function brain distribution of [(11)C]-N-desmethyl-loperamide but not (R)
      [(11)C]verapamil may depend on cerebral blood flow. In conclusion, we have
      identified a number of important factors, i.e., substrate affinity to ABCB1,
      brain uptake of radiolabeled metabolites, anesthesia, and cerebral blood flow,
      which can directly influence the magnitude of ABCB1-mediated DDIs at the BBB and
      should therefore be taken into consideration when interpreting PET results. 

PMID- 26202882
TI  - Downregulation of N-myc downstream regulated gene 1 caused by the methylation of
      CpG islands of NDRG1 promoter promotes proliferation and invasion of prostate
      cancer cells.
AB  - Current studies tend to consider N-myc downstream regulated gene 1 (NDRG1) as a
      tumor suppressor gene, inhibiting cell proliferation and invasion. NDRG1
      expression in cancer cells is generally low, but the molecular mechanism is
      unclear. Aberrant methylation of CpG islands (CGIs) in gene promoter was able to
      inactivate tumor suppressor genes and activate oncogenes, disordering cell
      proliferation and apoptosis, playing a promotion role in tumor occurrence and
      progression. The present study was performed to investigate the effect of
      epigenetic modification of NDRG1 on prostate cancer (PCa) cells. The protein
      expression in human specimens was measured by immunohistochemical staining. The
      expression level of NDRG1 was changed by plasmid vectors in PCa cells. These
      cells were used to study proliferation and invasiveness. NDRG1 expression in
      normal prostate cells was higher than that in PCa cells. Downregulation of NDRG1
      expression enhanced cell proliferation and invasiveness. In contrast, its
      upregulation could reduce cell proliferation and invasiveness. In PCa cells, the
      methylation rate of CGIs in the promoter region of NDRG1 was higher than that in
      normal prostate cells. 5-Aza-CdR, a methylation inhibitor, was able to
      effectively reverse the aberrant methylation of NDRG1, enhancing its expression,
      inhibiting cell growth. NDRG1 can inhibit the cell proliferation and invasion of
      PCa, but its expression level is low. The aberrant methylation of NDRG1 promoter
      is an important mechanism for gene silencing, playing an important role in tumor
      occurrence and progression. Therefore, reversing the aberrant methylation of
      NDRG1 may be used for PCa treatment. 

PMID- 26202884
TI  - The N-methyl-D-aspartate receptor's neglected subunit - GluN1 matters under
      normal and hyperbaric conditions.
AB  - Professional deep-water divers exposed to hyperbaric pressure (HP) above 1.1 MPa
      develop high-pressure neurological syndrome, which is associated with central
      nervous system hyperexcitability. It was previously reported that HP augments N
      methyl-D-aspartate receptor (NMDAR) synaptic responses, increases neuronal
      excitability, and potentially causes irreversible neuronal damage. In addition,
      we have reported that HP (10.1 MPa) differentially affects ionic currents,
      measured by the two-electrode voltage-clamp technique, of eight specific NMDAR
      subtypes generated by the co-expression of GluN1-1a or GluN1-1b with one of the
      four GluN2(A-D) subunits in Xenopus laevis oocytes. We now report that eight
      GluN1 splice variants, when co-expressed with GluN2A, mediate different ionic
      currents at normal and HP (5.1 MPa). These data, in conjunction with our previous
      results, indicate that both GluN1 and GluN2 subunits play a critical role in
      determining NMDAR currents under normal and HP conditions. These data, given the
      differential spatial distribution of the different NMDAR subtypes in the central
      nervous system, may offer a partial explanation for the mechanism governing the
      complex signs and symptoms of high-pressure neurological syndrome, and an
      explanation for the suspected long-term HP health decrement due to repetitive
      deep dives by professional divers. 

PMID- 26202883
TI  - Predominant structural configuration of natural antibody repertoires enables
      potent antibody responses against protein antigens.
AB  - Humoral immunity against diverse pathogens is rapidly elicited from natural
      antibody repertoires of limited complexity. But the organizing principles
      underlying the antibody repertoires that facilitate this immunity are not well
      understood. We used HER2 as a model immunogen and reverse-engineered murine
      antibody response through constructing an artificial antibody library encoded
      with rudimentary sequence and structural characteristics learned from high
      throughput sequencing of antibody variable domains. Antibodies selected in vitro
      from the phage-displayed synthetic antibody library bound to the model immunogen
      with high affinity and specificities, which reproduced the specificities of
      natural antibody responses. We conclude that natural antibody structural
      repertoires are shaped to allow functional antibodies to be encoded efficiently,
      within the complexity limit of an individual antibody repertoire, to bind to
      diverse protein antigens with high specificity and affinity. Phage-displayed
      synthetic antibody libraries, in conjunction with high-throughput sequencing, can
      thus be designed to replicate natural antibody responses and to generate novel
      antibodies against diverse antigens. 

PMID- 26202885
TI  - Prognosis of Possible Reassortments in Recent H5N2 Epidemic Influenza in USA:
      Implications for Computer-Assisted Surveillance As Well As Drug/Vaccine Design.
AB  - The recent H5N2 flu epidemic in US Midwest has led to deaths of millions of
      turkeys and farm bred poultry. While no human infections are reported to date,
      the rapid mutations in flu viruses can lead to more pathogenic subtypes. We have
      investigated such possibilities and have shown that H5N4, H5N9 and H5N6 are the
      most likely candidates for next round of viral reassortments, amongst which H5N9,
      if reassorted from Asiatic strains, could be highly pathogenic. We discuss here
      possibilities of anticipatory rational vaccine design based on work done earlier.

PMID- 26202886
TI  - Molecular Docking Reveals Binding Features of Estrogen Receptor Beta Selective
      Ligands.
AB  - Estrogen receptors exist as two subtypes ERalpha and ERbeta, which are
      characterized by various distributions in human tissues and diverse transcription
      regulation. Ligands capable of selective ERbeta activation show positive effects
      in treatment of such diseases as certain cancers, endometriosis, inflammatory
      diseases, and assist in maintaining cardiovascular and nervous system health.
      Thus far, there are no pharmaceutical drugs available acting on this target. In
      order to provide new treatment for such diseases, a new generation of selective
      estrogen receptor modulators is required. This remains an unsolved task due to
      several difficulties. It is known that minor modifications of ER agonists can
      influence the selectivity of their binding. The majority of designed ligands
      acting on ER possess chiral centers thus exist as stereoisomers. Unfortunately,
      not every spatial isomer is individually considered in experimental research. The
      molecular docking was applied to investigate the structural basis of diverse
      selectivity and binding affinity of selected estrogen receptor beta agonists.
      Docking simulations revealed that terminal aromatic rings positioned in the A-
      and D-ring regions are a factor that determines binding affinity of ERbeta
      agonists. This positioning can be ascribed to the presence of two terminal
      hydroxyl groups, a rigid linker, and the introduction of aliphatic substituents.
      The side substituents of underlined molecular scaffold should adopt inside
      characterized cavities I and II in order to provide selectivity. The bulkiness,
      attachment to linker and stereochemistry of the substituents affect ERbeta
      selectivity. These molecular features should be considered during search and
      design of new improved ERbeta agonists. 

PMID- 26202887
TI  - Prediction of Mutagenicity of Chemicals from Their Calculated Molecular
      Descriptors: A Case Study with Structurally Homogeneous versus Diverse Datasets.
AB  - Variation in high-dimensional data is often caused by a few latent factors, and
      hence dimension reduction or variable selection techniques are often useful in
      gathering useful information from the data. In this paper we consider two such
      recent methods: Interrelated two-way clustering and envelope models. We couple
      these methods with traditional statistical procedures like ridge regression and
      linear discriminant analysis, and apply them on two data sets which have more
      predictors than samples (i.e. n << p scenario) and several types of molecular
      descriptors. One of these datasets consists of a congeneric group of Amines while
      the other has a much diverse collection compounds. The difference of prediction
      results between these two datasets for both the methods supports the hypothesis
      that for a congeneric set of compounds, descriptors of a certain type are enough
      to provide good QSAR models, but as the data set grows diverse including a
      variety of descriptors can improve model quality considerably. 

PMID- 26202888
TI  - Challenges in optimizing care in advanced breast cancer patients: Results of an
      international survey linked to the ABC1 consensus conference.
AB  - Until recently, many international guidelines have focussed on the treatment of
      early-stage breast cancer, with little emphasis on advanced-stage disease. To
      improve the management of advanced breast cancer (ABC), the European School of
      Oncology (ESO) established the ABC International Consensus Conference and
      Guidelines. Delegates from the first conference and additional groups selected by
      ESO were invited to complete a survey to identify current challenges and barriers
      associated with optimizing ABC management. 609 Respondents from 78 countries
      completed the questionnaire. "Lack of clear and applicable management guidelines"
      and "lack of high-level evidence for treatment options" were identified as key
      barriers to raising the profile of ABC and treating the disease. The survey also
      revealed a lack of multidisciplinary treatment, specialized ABC nurses, and
      routine psychosocial support in clinical practice. Implementing high-quality
      guidelines could lead to better practice in the management of ABC by encouraging
      multidisciplinary treatment and patient-support initiatives. 

PMID- 26202889
TI  - Sirolimus-eluting dextran and polyglutamic acid hybrid coatings on AZ31 for stent
      applications.
AB  - Magnesium (Mg)-based cardiovascular stents are promising candidate as the next
      generation of novel stents. Clinical studies have revealed encouraging outcomes,
      but late restenosis and thrombogenesis still largely exist. Blood and vascular
      biocompatible coatings with drug-eluting features could be the solution to such
      problems. OBJECTIVE: This study was to investigate the feasibility of a three
      layer hybrid coating on Mg alloy AZ31 with sirolimus-eluting feature for
      cardiovascular stent application. MATERIALS AND METHODS: The first and third
      layers were low molecular weight dextran loaded with sirolimus, and the second
      layer was polyglutamic acid (PGA) to control sirolimus release. The hybrid
      coating was verified by scanning electron microscope (SEM). DC polarization and
      immersion tests were used to evaluate corrosion rate of the materials. Indirect
      cell viability and cell proliferation tests were performed by culturing cells
      with extract solutions of AZ31 samples. Blood compatibility was assessed using
      hemolysis assay. RESULTS: Coated samples had an enhanced corrosion resistance
      than that of uncoated controls, more PGA slower corrosion. Sirolimus had a burst
      release for the initial ~3 days and then a slower release until reached a
      plateau. The PGA thickness was able to control the sirolimus release, the thicker
      of PGA the slower release. The overall cell viability was extract concentration
      dependent, and improved by the hybrid coatings. Cell proliferation was correlated
      to coating thickness and was inhibited by sirolimus. In addition, all coated AZ31
      samples were non-hemolytic. CONCLUSION: Results demonstrated that such a three
      layer hybrid coating may be useful to improve the vascular biocompatibility of Mg
      stent materials.

PMID- 26202890
TI  - Gold nanostars mediated combined photothermal and photodynamic therapy and X-ray
      imaging for cancer theranostic applications.
AB  - Gold nanomaterials possess unique physical and chemical properties, which
      attracted much attention in recent years. As a new type of gold nanomaterials,
      gold nanostars (GNSTs) have been prepared and characterized in this study. GNSTs
      under near-infrared (NIR) light irradiation can exert not only cancer
      photothermal therapy via heat production but also photodynamic therapy via
      generation of reactive oxygen species. GNSTs were able to enter the cytoplasm as
      well as nuclei of human breast michigan cancer foundation-7 (MCF-7) cells. Under
      NIR light irradiation, GNSTs caused more severe DNA damage, arrest the cell cycle
      in G0/G1 phase, and reduce more cellular glutathione level, causing more severe
      apoptosis and cell death in vitro. Intratumoral injection of GNSTs with NIR light
      irradiation significantly inhibited tumor growth in vivo. In addition, GNSTs were
      demonstrated to be a contrast agent for X-ray imaging. All the in vitro and in
      vivo results showed that GNSTs can be used for the potential diagnosis and
      medical treatment of cancer.

PMID- 26202891
TI  - The endocannabinoid anandamide affects the synthesis of human syncytiotrophoblast
      related proteins.
AB  - The human syncytiotrophoblast (hST) has a major role in the production of
      important placental hormones. Several molecules regulate hST endocrine function
      but the role of endocannabinoids in this process is still unknown. Here, we
      report that the endocannabinoid anandamide (AEA) decreased cAMP levels, impaired
      human chorionic gonadotropin secretion, placental alkaline phosphatase activity
      and decreased aromatase mRNA levels and protein expression, through cannabinoid
      (CB) receptor activation. AEA also downregulated leptin and placental protein 13
      transcription, though via a CB receptor-independent mechanism. All this evidence
      suggests AEA is a novel modulator of hormone synthesis by the
      syncytiotrophoblast, supporting the importance of the endocannabinoid signalling
      in placental function. 

PMID- 26202892
TI  - Acute myocardial infarction does not affect functional characteristics of adipose
      derived stem cells in rats, but reduces the number of stem cells in adipose
      tissue.
AB  - In most pre-clinical animal studies investigating stem cell therapy in acute
      myocardial infarction (AMI), the administered stem cells are isolated from
      healthy donors. In clinical practice, however, patients who suffer from AMI will
      receive autologous cells, for example using adipose-derived stem cells (ASC).
      During AMI, inflammation is induced and we hypothesized that this might affect
      characteristics of ASC. To investigate this, ASC were isolated from rat adipose
      tissue 1 day (1D group, n = 5) or 7 days (7D group, n = 6) post-AMI, and were
      compared with ASC from healthy control rats (Control group, n = 6) and sham
      operated rats (Sham 1D group, n = 5). We found that significantly fewer ASC were
      present 1 day post-AMI in the stromal vascular fraction (SVF), determined by a
      colony-forming-unit assay (p < 0.001 vs. Control and 7D). These data were
      confirmed by flow cytometry, showing fewer CD90-positive cells in SVF of the 1D
      group. When cultured, no differences were found in proliferation rate and cell
      size between the groups in the first three passages. Also, no difference in the
      differentiation capacity of ASC was found. In conclusion, it was shown that
      significantly fewer stem cells were present in the SVF 1 day post-AMI; however,
      the stem cells that were present showed no functional differences.

PMID- 26202893
TI  - Characterization of miRNA processing machinery in the embryonic chick lung.
AB  - Lung development is a very complex process that relies on the interaction of
      several signaling pathways that are controlled by precise regulatory mechanisms.
      Recently, microRNAs (miRNAs), small non-coding regulatory RNAs, have emerged as
      new players involved in gene expression regulation controlling several biological
      processes, such as cellular differentiation, apoptosis and organogenesis, in both
      developmental and disease processes. Failure to correctly express some specific
      miRNAs or a component of their biosynthetic machinery during embryonic
      development is disastrous, resulting in severe abnormalities. Several miRNAs have
      already been identified as modulators of lung development. Regarding the spatial
      distribution of the processing machinery of miRNAs, only two of its members
      (dicer1 and argonaute) have been characterized. The present work characterizes
      the expression pattern of drosha, dgcr8, exportin-5 and dicer1 in early stages of
      the embryonic chick lung by whole mount in situ hybridization and cross-section
      analysis. Overall, these genes are co-expressed in dorsal and distal mesenchyme
      and also in growing epithelial regions. The expression pattern of miRNA
      processing machinery supports the previously recognized regulatory role of this
      mechanism in epithelial and mesenchymal morphogenesis. 

PMID- 26202895
TI  - In situ visualisation of electromigration in Pt nanobridges at elevated
      temperatures.
AB  - We used a combination of in situ TEM, a MEMS-based heater as a substrate and a
      dedicated biasing sample holder to study the temperature dependence of
      electromigration in Pt nanobridges (500 nm wide, 15 nm high and 1000 nm long). We
      visualised changes in the nanobridges under both dynamic conditions, i.e. heating
      (substrate temperatures up to 660 K) and current passage. Our electromigration
      experiments at various substrate temperatures (100, 300, 420 and 660 K) show the
      same tendency: material transport occurs from the cathode to the anode side,
      which can be explained by the electron-wind force. In all cases the bridge breaks
      due to the formation of a neck closer to the cathode side. At 300, 420 and 660 K,
      voids and the neck form at the cathode contact pad simultaneously. The higher the
      temperature, the bigger the voids size. As expected, at higher temperatures a
      lower power is needed to break the nanobridge.

PMID- 26202894
TI  - Factors associated with atypical femoral fracture.
AB  - We aimed to investigate the proportion of atypical femoral fractures (AFF) among
      Korean femoral fracture patients and examined the factors associated with the
      development of AFF. Between 2003 and 2013, 607 female patients with low-energy
      femoral fractures who were hospitalized at a single university hospital were
      retrospectively enrolled in this study. Patients were classified into two groups
      according to the fracture site: Patients with subtrochanteric or diaphyseal
      femoral fractures were included in the AFF group, while patients with
      intertrochanteric or neck fractures were included in the typical femoral fracture
      (TFF) group. After comparing clinical and radiographic characteristics between
      groups, we used multivariable logistic regression analysis to explore risk
      factors for AFF. Thirty patients (4.9 %) with AFF and 577 patients (95.1 %) with
      TFF were identified. The AFF group was younger than the TFF group (p < 0.01), and
      more patients with AFF were treated with bisphosphonate (BP) (p < 0.01) or proton
      pump inhibitor (p = 0.02). When comparing the radiographic parameters, the AFF
      group tended to have a higher cortical thickness index (p = 0.02) and lateral-to
      medial cortex ratio (p < 0.01). After adjusting for clinical variables, BP use
      (OR 8.09, CI 3.09-21.19) and younger age (OR 1.06, CI 1.01-1.11) were associated
      with AFF. The proportion of AFF was 4.9 % among patients with femoral fractures.
      Younger age and use of BP before fracture increased the risk of development of
      AFF in Korean patients.

PMID- 26202896
TI  - Electron tomography based on highly limited data using a neural network
      reconstruction technique.
AB  - Gold nanoparticles are studied extensively due to their unique optical and
      catalytical properties. Their exact shape determines the properties and thereby
      the possible applications. Electron tomography is therefore often used to examine
      the three-dimensional (3D) shape of nanoparticles. However, since the acquisition
      of the experimental tilt series and the 3D reconstructions are very time
      consuming, it is difficult to obtain statistical results concerning the 3D shape
      of nanoparticles. Here, we propose a new approach for electron tomography that is
      based on artificial neural networks. The use of a new reconstruction approach
      enables us to reduce the number of projection images with a factor of 5 or more.
      The decrease in acquisition time of the tilt series and use of an efficient
      reconstruction algorithm allows us to examine a large amount of nanoparticles in
      order to retrieve statistical results concerning the 3D shape. 

PMID- 26202897
TI  - Immune-Mediated Neurological Disorders.
AB  - Autoimmune disorders are increasingly recognized causes of several neurological
      disorders leading to significant clinical disability. This article reviews recent
      developments in our understanding on the pathophysiology, clinical presentations,
      and diagnoses of selected immune-mediated neurological disorders. It also
      provides a brief summary of current theories on autoimmunity and the role that
      certain environmental factors play in the development of immune-mediated
      neurological disorders. Recently recognized biomarkers might play a pathogenetic
      role or simply serve as a diagnostic tool. 

PMID- 26202898
TI  - Treatment of Lateral Epicondylosis by Using Allogeneic Adipose-Derived
      Mesenchymal Stem Cells: A Pilot Study.
AB  - Mesenchymal stem cell therapy is a novel regenerative approach for treating
      tendinopathy. Here, we evaluated the safety and efficacy of allogeneic adipose
      derived mesenchymal stem cells (allo-ASC) in treating lateral epicondylosis (LE).
      Under ultrasound guidance, allo-ASCs mixed with fibrin glue were injected into
      the hypoechoic common extensor tendon lesions of 12 participants with chronic LE;
      6 subjects each were administered 10(6) or 10(7) cells in 1 ml. Safety was
      evaluated at day 3 and weeks 2, 6, 12, 26, and 52 post-injection. Efficacy was
      assessed by measuring patients' visual analog scale (VAS) score for elbow pain,
      modified Mayo clinic performance index for the elbow, and by evaluating
      longitudinal and transverse ultrasound images of tendon defect areas after 6, 12,
      26, and 52 weeks. No significant adverse effects of allo-ASC injection were
      observed through 52 weeks of follow-up. From baseline through 52 weeks of
      periodic follow-up, VAS scores progressively decreased from 66.8 +/- 14.5 mm to
      14.8 +/- 13.1 mm and elbow performance scores improved from 64.0 +/- 13.5 to 90.6
      +/- 5.8. Tendon defects also significantly decreased through this period. Allo
      ASC therapy was thus safe and effective in improving elbow pain, performance, and
      structural defects for 52 weeks. This clinical study is the first to reveal
      therapeutic value of mesenchymal stem cell injection for treating chronic
      tendinopathy.

PMID- 26202899
TI  - Susceptibility-Weighted MRI for Deep Brain Stimulation: Potentials in Trajectory
      Planning.
AB  - BACKGROUND: Deep brain stimulation (DBS) trajectory planning is mostly based on
      standard 3-D T1-weighted gadolinium-enhanced MRI sequences (T1-Gd).
      Susceptibility-weighted MRI sequences (SWI) show neurovascular structures without
      the use of contrast agents. The aim of this study was to investigate whether SWI
      might be useful in DBS trajectory planning. METHODS: We performed bilateral DBS
      planning using conventional T1-Gd images of 10 patients with different kinds of
      movement disorders. Afterwards, we matched SWI sequences and compared the
      visibility of vascular structures in both imaging modalities. RESULTS: By
      analyzing 100 possible trajectories, we found a potential vascular conflict in 13
      trajectories based on T1-Gd in contrast to 53 in SWI. Remarkably, all vessels
      visible in T1-Gd were also depicted in SWI, whereas SWI showed many additional
      vascular structures which could not be identified in T1-Gd.
      CONCLUSION/DISCUSSION: The sensitivity for detecting neurovascular structures for
      DBS planning seems to be significantly higher in SWI. As SWI does not require a
      contrast agent, we suggest that SWI may be a valuable alternative to T1-Gd MRI
      for DBS trajectory planning. Furthermore, the data analysis suggests that
      vascular interactions of DBS trajectories might be more frequent than expected
      from the very low incidence of symptomatic bleedings. The explanation for this is
      currently the subject of debate and merits further studies.

PMID- 26202900
TI  - Fiber-based laser speckle imaging for the detection of pulsatile flow.
AB  - BACKGROUND AND OBJECTIVE: In endodontics, a major diagnostic challenge is the
      accurate assessment of pulp status. In this study, we designed and characterized
      a fiber-based laser speckle imaging system to study pulsatile blood flow in the
      tooth. STUDY DESIGN/MATERIALS AND METHODS: To take transilluminated laser speckle
      images of the teeth, we built a custom fiber-based probe. To assess our ability
      to detect changes in pulsatile flow, we performed in vitro and preliminary in
      vivo tests on tissue-simulating phantoms and human teeth. We imaged flow of
      intralipid in a glass microchannel at simulated heart rates ranging from 40
      beats/minute (bpm) to 120 bpm (0.67-2.00 Hz). We also collected in vivo data from
      the upper front incisors of healthy subjects. From the measured raw speckle data,
      we calculated temporal speckle contrast versus time. With frequency-domain
      analysis, we identified the frequency components of the contrast waveforms.
      RESULTS: With our approach, we observed in vitro the presence of pulsatile flow
      at different simulated heart rates. We characterized simulated heart rate with an
      accuracy of and >98%. In the in vivo proof-of-principle experiment, we measured
      heart rates of 69, 90, and 57 bpm, which agreed with measurements of subject
      heart rate taken with a wearable, commercial pulse oximeter. CONCLUSIONS: We
      designed, built, and tested the performance of a dental imaging probe. Data from
      in vitro and in -vivo tests strongly suggest that this probe can detect the
      presence of pulsatile flow. LSI may enable endodontists to noninvasively assess
      pulpal vitality via direct measurement of blood flow.

PMID- 26202902
TI  - Temperature influences the level of glyphosate resistance in barnyardgrass
      (Echinochloa colona).
AB  - BACKGROUND: Echinochloa colona is an important summer-growing weed species in
      cropping regions of northern Australia that has evolved resistance to glyphosate
      owing to intensive use of this herbicide in summer fallow. RESULTS: Pot trials
      conducted at 20 and 30  degrees C on six E. colona populations showed a
      significant increase in the level of glyphosate resistance in resistant
      populations at 30  degrees C compared with 20  degrees C. However, there was no
      influence of growth temperature on glyphosate susceptibility of the sensitive
      population. Sequencing of the target-site gene (EPSPS) of the six populations
      identified a mutation at position 106 leading to a change from proline to serine
      in the most resistant population A533.1 only. EPSPS gene amplification was not
      detected in any of the resistant populations examined. Examining (14) C
      glyphosate uptake on two resistant and one susceptible population showed a
      twofold increase at 20  degrees C; however, few differences in glyphosate
      translocation occurred from the treated leaf to other plant parts between
      populations or temperatures. CONCLUSION: There is reduced efficacy of glyphosate
      at high temperatures on resistant E. colona populations, making these populations
      harder to control in summer.

PMID- 26202903
TI  - Dental treatment under general anesthesia for special-needs patients: analysis of
      the literature.
AB  - The aim of the present review was to identify the studies published on dental
      treatment under general anesthesia for special-needs patients. A comprehensive
      search of the reported literature from January 1966 to May 2012 was conducted
      using PubMed, Medline, and Embase. Keywords used in the search were "dental
      treatment under general anesthesia", "special-needs patients", "medically
      compromised patients", and "children", in various combinations. Studies published
      only on dental treatment under general anesthesia and in English were included.
      Only 10 studies were available for final analysis. Age range from 1 to 50 years,
      and restorative procedures, were most prevalent. Only two studies discussed
      repeated general anesthesia, with rates of 7.2% and 10.2%. Over time, the
      provision of general anesthesia for special-needs patients has changed from
      dental clinics to general hospitals. The demand for dental treatment for special
      needs patients under general anesthesia continues to increase. Currently, there
      are no certain accepted protocols for the provision of dental treatment under
      general anesthesia.

PMID- 26202904
TI  - Distinctive clinical characteristics of malignant mesothelioma in young patients.
AB  - Although considered a disease of the elderly, a subset of patients with
      mesothelioma are young (<40 years). The goal of this study was to understand
      their characteristics and outcomes. The Surveillance, Epidemiology, and End
      Results (SEER) database was used to extract mesothelioma cases (1990-2010). We
      modeled Kaplan-Meyer survival curves stratified by site of disease, and age of
      presentation. 2% (207 of 12345) of mesothelioma patients are young. Sex
      distribution is comparable among the young (51% males, 49% females); males
      predominated (78%, 22%) in the older cohort. Frequency of pleural and peritoneal
      mesothelioma are similar in the young (47%, 48% respectively); pleural disease
      predominated in the old (90%, 9%). Cancer-directed surgeries are more frequent in
      the young. Regardless of histologic subtype, young patients with pleural (11 vs.
      8 months) and peritoneal (not reached vs. 10 months) mesothelioma had
      significantly improved overall survival. In multivariate analysis, younger age
      was an independent prognostic factor. Although rare, mesothelioma do occur in the
      young; their characteristics are distinct from those of older patients. Further
      studies are needed to understand the interplay between genetic susceptibility and
      mineral fiber carcinogenesis in the pathogenesis of mesothelioma in the young.

PMID- 26202906
TI  - The meaning of early intervention: A parent's experience and reflection on
      interactions with professionals using a phenomenological ethnographic approach.
AB  - The purpose of this study is to describe how a parent's partnership with
      professionals progresses and evolves throughout the service provisioning process.
      Using a phenomenological ethnographic approach, the lived reality of a family is
      depicted as the parent walks through different stages of the Individualized
      Family Service Plan process over a 6-month period. Data concerning parent
      professional interactions were obtained via observation notes and document
      reviews whereas data regarding parent perceptions were collected through multiple
      individual interviews. Overall, the parent conveyed her satisfaction with actual
      services especially regarding the professionals' knowledge and parental advocacy.
      However, the parent also indicated frustration with the early intervention
      planning process and "obligated" partnerships with providers. In particular, the
      providers' lack of sensitivity was noted, and greater emotional and psychological
      support was suggested. The overall process of developing partnerships with
      professionals can be excessively intrusive to the family's lives. Future research
      directions are offered as a contribution for the development of improved policies
      for early intervention programs regarding family-centered practice, utilizing the
      perspectives of families. 

PMID- 26202905
TI  - Computation of pH-dependent binding free energies.
AB  - Protein-ligand binding accompanies changes in the surrounding electrostatic
      environments of the two binding partners and may lead to changes in protonation
      upon binding. In cases where the complex formation results in a net transfer of
      protons, the binding process is pH-dependent. However, conventional free energy
      computations or molecular docking protocols typically employ fixed protonation
      states for the titratable groups in both binding partners set a priori, which are
      identical for the free and bound states. In this review, we draw attention to
      these important yet largely ignored binding-induced protonation changes in
      protein-ligand association by outlining physical origins and prevalence of the
      protonation changes upon binding. Following a summary of various theoretical
      methods for pKa prediction, we discuss the theoretical framework to examine the
      pH dependence of protein-ligand binding processes.

PMID- 26202907
TI  - Fe(2+) substrate transport through ferritin protein cage ion channels influences
      enzyme activity and biomineralization.
AB  - Ferritins, complex protein nanocages, form internal iron-oxy minerals
      (Fe2O3.H2O), by moving cytoplasmic Fe(2+) through intracage ion channels to cage
      embedded enzyme (2Fe(2+)/O2 oxidoreductase) sites where ferritin
      biomineralization is initiated. The products of ferritin enzyme activity are
      diferric oxy complexes that are mineral precursors. Conserved, carboxylate amino
      acid side chains of D127 from each of three cage subunits project into ferritin
      ion channels near the interior ion channel exits and, thus, could direct Fe(2+)
      movement to the internal enzyme sites. Ferritin D127E was designed and analyzed
      to probe properties of ion channel size and carboxylate crowding near the
      internal ion channel opening. Glu side chains are chemically equivalent to, but
      longer by one -CH2 than Asp, side chains. Ferritin D127E assembled into normal
      protein cages, but diferric peroxo formation (enzyme activity) was not observed,
      when measured at 650 nm (DFP lambda max). The caged biomineral formation,
      measured at 350 nm in the middle of the broad, nonspecific Fe(3+)-O absorption
      band, was slower. Structural differences (protein X-ray crystallography), between
      ion channels in wild type and ferritin D127E, which correlate with the inhibition
      of ferritin D127E enzyme activity include: (1) narrower interior ion channel
      openings/pores; (2) increased numbers of ion channel protein-metal binding sites,
      and (3) a change in ion channel electrostatics due to carboxylate crowding. The
      contributions of ion channel size and structure to ferritin activity reflect
      metal ion transport in ion channels are precisely regulated both in ferritin
      protein nanocages and membranes of living cells. 

PMID- 26202908
TI  - Gold(I) NHC-based homo- and heterobimetallic complexes: synthesis,
      characterization and evaluation as potential anticancer agents.
AB  - While N-heterocyclic carbenes (NHC) are ubiquitous ligands in catalysis for
      organic or industrial syntheses, their potential to form transition metal
      complexes for medicinal applications has still to be exploited. Within this
      frame, we synthesized new homo- and heterobimetallic complexes based on the Au(I)
      NHC scaffold. The compounds were synthesized via a microwave-assisted method
      developed in our laboratories using Au(I)-NHC complexes carrying a
      pentafluorophenol ester moiety and another Au(I) phosphane complex or a
      bipyridine ligand bearing a pendant amine function. Thus, we developed two
      different methods to prepare homo- and heterobimetallic complexes (Au(I)/Au(I) or
      Au(I)/Cu(II), Au(I)/Ru(II), respectively). All the compounds were fully
      characterized by several spectroscopic techniques including far infrared, and
      were tested for their antiproliferative effects in a series of human cancer
      cells. They showed moderate anticancer properties. Their toxic effects were also
      studied ex vivo using the precision-cut tissue slices (PCTS) technique and
      initial results concerning their reactivity with the seleno-enzyme thioredoxin
      reductase were obtained. 

PMID- 26202909
TI  - Clinical predictors and outcomes of patients with left ventricular thrombus
      following ST-segment elevation myocardial infarction.
AB  - We aimed to characterize the independent predictors of LVT following STEMI and
      the association with outcomes. The clinical predictors of left ventricular
      thrombus (LVT) formation after ST-segment elevation myocardial infarction (STEMI)
      are not well-defined in the contemporary era. We performed a retrospective
      analysis of STEMI patients at Duke from 2000 to 2011 who had a transthoracic
      echocardiogram within 90 days post-STEMI and compared patients with and without
      LVT (LVT+ vs. LVT-). Univariate Cox proportional hazards regression models of
      baseline characteristics were examined and significant variables were used in a
      multivariable model to assess adjusted relationships with LVT. A multivariable
      Cox PH survival model with covariate adjustments was used for assessment of LVT
      and long-term mortality. Of all eligible patients, 1734 patients met inclusion
      criteria and 4.3 % (N = 74) had a LVT. LVT+ patients tended to have a history of
      heart failure (HF) and higher initial troponin compared to LVT- patients. After
      adjustment, higher heart rate, non-white race, HF severity, and presence of left
      anterior descending artery (LAD) disease were independent predictors of LVT.
      There was a trend toward an association between LVT and increased all-cause
      mortality (HR 1.36; 95 % CI 0.84-2.21, P = 0.22), however this was not
      statistically significant. LVT was seen in over 4 % of this contemporary post
      STEMI population. Several baseline characteristics were independently associated
      with LVT: Heart rate, HF severity, LAD disease, and non-white race. Prospective
      studies are warranted to determine whether anticoagulation in patients at
      increased risk for LVT improves outcomes.

PMID- 26202911
TI  - Optical tracking of phagocytosis with an activatable profluorophore metabolically
      incorporated into bacterial peptidoglycan.
AB  - Phagocytosis is critical for immunity against pathogens. Prior imaging using dye
      labeled synthetic beads or green fluorescent protein-expressing bacteria is
      limited by "always-on" signals which compromise discerning phagocytosed particles
      from adherent particles. Targeting cellular internalization of pathogens into
      acidic phagolysosomes, we herein report "turn-on" fluorescence imaging of
      phagocytosis with viable bacteria featuring peptidoglycans covalently modified
      with rhodamine-lactam responsive to acidic pH. Culturing of Escherichia coli (E.
      coli) and Staphylococcus aureus (S. aureus) with d-lysine conjugated rhodamine
      lactam and fluorescein isocyanate (FITC) leads to efficient metabolic
      incorporation of FITC and rhodamine-lactam into bacterial peptidoglycan. E. coli
      and S. aureus become red-emissive upon phagocytosis into Raw 264.7 macrophages.
      With FITC as the reference signal, the mono- and dual-color emission allow
      efficient in situ distinction of ingested bacteria from extracellular bacteria.
      Given the ease of optical peptidoglycan labeling, the prevalence of microbial
      peptidoglycan and preservation of microbial surface landscape, this approach
      would be of use for investigation on microbial pathogenesis and high-throughput
      screening of immunomodulators of phagocytosis. 

PMID- 26202910
TI  - IRGM1 enhances B16 melanoma cell metastasis through PI3K-Rac1 mediated epithelial
      mesenchymal transition.
AB  - Melanoma is one of the most aggressive skin cancers and is well known for its
      high metastatic rate. Studies have shown that epithelial mesenchymal transition
      (EMT) is essential for melanoma cell metastasis. However, the molecular
      mechanisms underlying EMT are still not fully understood. We have shown that
      IRGM1, a member of immunity-related GTPase family that regulates immune cell
      motility, is highly expressed by melanoma cells. The current study aimed to
      explore whether and how IRGM1 may regulate melanoma cell metastasis. To test
      this, we modified IRGM1 expression in B16 melanoma cells. We found that over
      expression of IRGM1 substantially enhanced pulmonary metastasis in vivo. In
      keeping with that, knocking-in IRGM1 strongly enhanced while knocking-down IRGM1
      impaired B16 cell migration and invasion ability in vitro. Interestingly, we
      observed that IRGM1 enhanced F-actin polymerization and triggers epithelial
      mesenchymal transition (EMT) through a mechanism involved in PIK3CA mediated Rac1
      activation. Together, these data reveals a novel molecular mechanism that
      involved in melanoma metastasis. 

PMID- 26202912
TI  - Serum anti-Mullerian hormone production is not correlated with seasonal
      fluctuations of vitamin D status in ovulatory or PCOS women.
AB  - STUDY QUESTION: Is there a relationship between serum anti-Mullerian hormone
      (AMH) levels and seasonal variations in serum vitamin D in ovulatory and
      polycystic ovary syndrome (PCOS) women? STUDY ANSWER: Serum AMH levels were not
      associated with serum vitamin D status even after controlling for relevant co
      variants, with this finding being consistent for all causes of infertility. As
      expected, seasonal variations in serum vitamin D were observed between summer and
      winter. WHAT IS KNOWN ALREADY: AMH plays an important role in maintaining ovarian
      reserve and modifying follicle sensitivity to FSH stimulation. Studies suggest
      that vitamin D has the ability to modify AMH production in vitro, yet only one
      clinical study reports the influence of vitamin D on AMH levels. STUDY DESIGN,
      SIZE, DURATION: This was a retrospective cohort study analyzing the potential
      interaction of AMH and vitamin D for 340 women (58 PCOS and 282 ovulatory women)
      aged less than 40 years collected as part of their routine fertility assessment
      between January and December 2013 at a private fertility clinic in Adelaide,
      South Australia. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patient data including
      age, BMI, cause of infertility, antral follicle counts (AFC), serum AMH and
      vitamin D levels, smoking status, and menstrual cycle length for women aged less
      than 40 years of age, with serum AMH and vitamin D sampled within the same 4-week
      period were retrieved from a database. The hours of sunlight per day and daily UV
      index were extracted from a database at the South Australian Bureau of
      Meteorology, South Australia. Serum vitamin D (25-hydroxyvitamin D) levels were
      analyzed against seasonal variation in sunlight and UV exposure and serum AMH
      levels, while controlling for relevant co-variants. MAIN RESULTS AND THE ROLE OF
      CHANCE: Seasonal variations in serum vitamin D were observed between summer and
      winter (30% variance; P < 0.001), while serum AMH levels (mean +/- SEM) remained
      unaffected by season status (36.9 +/- 3.3 versus 38.5 +/- 2.7 pmol/l; P > 0.05),
      even after controlling for relevant co-variants. Overall, no correlation was
      observed between serum AMH and vitamin D levels, in either the PCOS or ovulatory
      cohort. Serum vitamin D levels were not significantly related to the underlying
      cause of infertility (PCOS, diminished ovarian reserve, 'fertile' ovulatory
      controls). LIMITATIONS, REASONS FOR CAUTION: The data used to generate the study
      findings are cross sectional in nature. While we acknowledge that a longitudinal
      study monitoring the relationship between serum AMH and vitamin D in individuals
      over the four seasons would have been ideal, we believe the current findings are
      robust as our four seasonal groups did not differ for any significant co-variant
      for serum AMH or vitamin D (age, BMI, PCOS status or AFC) and that there is no
      significant association between serum vitamin D concentration and AMH production.
      WIDER IMPLICATIONS OF THE FINDINGS: At present, while in vitro studies suggest
      vitamin D has the potential to modify AMH production, clinical study findings are
      conflicting. If vitamin D does influence AMH production, this could have
      important therapeutic implications. STUDY FUNDING/COMPETING INTERESTS: K.G. was
      supported through a University of South Australia summer scholarship. The authors
      have no competing interests.

PMID- 26202913
TI  - Mental disorders in childhood and young adulthood among children born to women
      with fertility problems.
AB  - STUDY QUESTION: Is the risk of hospital admission or outpatient contact for
      mental disorders increased in children born to women with fertility problems
      compared with children born to women without fertility problems? SUMMARY ANSWER:
      We found an increased risk of hospital admission or outpatient contact for mental
      disorders in children born to women with fertility problems. WHAT IS KNOWN
      ALREADY: Few studies have investigated the risk of mental disorders in children
      born after fertility treatment and although some studies have pointed to an
      increased risk, others found no association. The inconsistent results may be due
      to methodological constraints in many previous studies, including small sample
      size and short follow-up, resulting in imprecise risk estimates and lack of
      information on risk patterns of mental disorders in adulthood. STUDY DESIGN,
      SIZE, DURATION: This nationwide retrospective register-based cohort study
      included all 2 412 721 children born in Denmark between 1969 and 2006. All
      children were followed from date of birth until date of hospital contact for a
      mental disorder, date of emigration, date of death or 31 December 2009, whichever
      occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information concerning
      maternal fertility status for all children in the cohort was obtained by linkage
      to the Danish Infertility Cohort, which contains data on nearly all women with
      fertility problems in Denmark since 1963. A total of 124 269 (5%) children were
      born to women with fertility problems and 2 288 452 (95%) to women without
      fertility problems. To identify children hospitalized for a mental disorder, the
      cohort was linked to the Danish Psychiatric Central Research Registry. Cox
      proportional hazards models were used to estimate hazard ratios (HRs) and 95%
      confidence intervals (CIs) for the association between maternal fertility status
      and the risk of hospital admission or outpatient contact for various groups of
      mental disorders, including any mental disorder and all 11 main discharge
      diagnostic groups, classified according to the International Classification of
      Diseases, version 10. MAIN RESULTS AND THE ROLE OF CHANCE: During a mean follow
      up period of 21 years (range, 0-40 years), 168 686 (7%) children were admitted to
      hospital or had an outpatient contact for a mental disorder. Children born to
      women with fertility problems had a significantly higher risk of any mental
      disorder (HR 1.23; 95% CI 1.20-1.26) and for most of the 11 main discharge
      groups, including schizophrenia (HR 1.16; 95% CI 1.07-1.27), mood (affective)
      disorders (HR 1.21; 95% CI 1.15-1.28) and disorders of psychological development
      (HR 1.15; 95% CI 1.09-1.21) as well as the subgroup of attention
      deficit/hyperactivity disorders (HR 1.36; 95% CI 1.29-1.45) compared with
      children born to women without fertility problems. The risk estimates did not
      change markedly when analyses were performed separately for mental disorders
      diagnosed during childhood (0-19 years) and in young adulthood (20-40 years).
      LIMITATIONS, REASON FOR CAUTION: The true risk of mental disorders may be
      somewhat underestimated, as only severe disorders requiring hospital admission or
      outpatient contact were considered as events. Furthermore, we could not determine
      whether the increased risks observed were due to factors related to the
      underlying infertility or to fertility treatment procedures. WIDER IMPLICATIONS
      OF THE FINDINGS: This is the first report on mental disorders in adulthood among
      children born to women with fertility problems. Furthermore, we have assessed the
      risk of several severe mental disorders not previously studied (e.g. neurotic,
      stress-related and somatoform disorders and disorders of adult personality and
      behaviour). These important findings should be investigated further in large
      epidemiological studies designed to differentiate between factors related to
      fertility treatment and to the underlying infertility. STUDY FUNDING/COMPETING
      INTERESTS: The study was supported by internal funding from the Unit of Virus,
      Lifestyle and Genes at the Danish Cancer Society Research Center. All authors
      report no conflicts of interest.

PMID- 26202914
TI  - Stem cells in reproductive medicine: ready for the patient?
AB  - STUDY QUESTION: Are there effective and clinically validated stem cell-based
      therapies for reproductive diseases? SUMMARY ANSWER: At the moment, clinically
      validated stem cell treatments for reproductive diseases and alterations are not
      available. WHAT IS KNOWN ALREADY: Research in stem cells and regenerative
      medicine is growing in scope, and its translation to the clinic is heralded by
      the recent initiation of controlled clinical trials with pluripotent derived
      cells. Unfortunately, stem cell 'treatments' are currently offered to patients
      outside of the controlled framework of scientifically sound research and
      regulated clinical trials. Both physicians and patients in reproductive medicine
      are often unsure about stem cells therapeutic options. STUDY DESIGN, SIZE,
      DURATION: An international working group was assembled to review critically the
      available scientific literature in both the human species and animal models.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: This review includes work published in
      English until December 2014, and available through Pubmed. MAIN RESULTS AND THE
      ROLE OF CHANCE: A few areas of research in stem cell and reproductive medicine
      were identified: in vitro gamete production, endometrial regeneration, erectile
      dysfunction amelioration, vaginal reconstruction. The stem cells studied range
      from pluripotent (embryonic stem cells and induced pluripotent stem cells) to
      monopotent stem cells, such as spermatogonial stem cells or mesenchymal stem
      cells. The vast majority of studies have been carried out in animal models, with
      data that are preliminary at best. LIMITATIONS, REASONS FOR CAUTION: This review
      was not conducted in a systematic fashion, and reports in publications not
      indexed in Pubmed were not analyzed. WIDER IMPLICATIONS OF THE FINDINGS: A much
      broader clinical knowledge will have to be acquired before translation to the
      clinic of stem cell therapies in reproductive medicine; patients and physicians
      should be wary of unfounded claims of improvement of existing medical conditions;
      at the moment, effective stem cell treatment for reproductive diseases and
      alterations is not available. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL
      REGISTRATION NUMBER: NA.

PMID- 26202916
TI  - Risk of recurrent molar pregnancies following complete and partial hydatidiform
      moles.
AB  - STUDY QUESTION: What is the risk of further molar pregnancies for women with one
      or more hydatidiform moles (HM) in relation to molar subtype. SUMMARY ANSWER:
      Women with a complete hydatidiform mole (CM) have a 1 in 100 and 1 in 4 risk of
      further CM after one or two consecutive CM, respectively, while women with a
      partial hydatidiform mole (PM) have only a small increase in risk for further
      molar pregnancies. WHAT IS KNOWN ALREADY: Women with a molar pregnancy have an
      increased risk of further HM. A small subgroup of women with recurrent HM has an
      autosomal recessive condition, familial recurrent hydatidiform moles (FRHM), that
      predisposes them to molar pregnancies. STUDY DESIGN, SIZE, DURATION: A
      retrospective study of subsequent pregnancies in 16 000 women registered at a
      centralized referral centre, with a CM or PM, between 1990 and 2009.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and sixty-six women with
      two or more molar pregnancies were identified from electronic records and patient
      notes. Histopathological features of all molar tissue were reviewed in these
      cases and genotyping performed where diagnosis was not possible on the basis of
      histopathological features alone. In addition, genotyping of molar tissue was
      performed in all cases of women with three or more CM to establish whether the
      tissue was diploid and biparental or androgenetic. MAIN RESULTS AND THE ROLE OF
      CHANCE: This study confirms an increased recurrence risk of ~1% for a second
      molar pregnancy and in addition that this risk is associated with CM rather than
      PM. The data further indicate that the risk of a third HM is associated almost
      exclusively with CM and enabled an estimate that 1 in 640 women registered with a
      CM has the rare condition FRHM. The study also found that there was no
      significant difference between the risk of developing gestational trophoblastic
      neoplasia (GTN) for typical sporadic CM and the diploid biparental CM associated
      with FRHM (GTN; proportion difference 0.05, Z = 0.87, P = 0.29). LIMITATIONS,
      REASONS FOR CAUTION: While pathology was reviewed for all women with two or more
      molar pregnancies, not all cases registered underwent central review particularly
      those women registered in the early 1990s. It is therefore possible that the
      total number of CM and PM may differ slightly from that stated. While women were
      followed for a minimum of 5 years, it is possible that some women may
      subsequently have further molar pregnancies that will not have been included in
      the present study. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study
      to date on recurrence for molar pregnancies, and as such provides the most
      detailed information so far regarding the risk of further molar pregnancies for
      women with a PM or CM. Furthermore, the data provide new insights into the
      incidence of the rare autosomal recessive condition, FRHM, important information
      for counselling women with molar pregnancies. STUDY FUNDING/COMPETING INTERESTS:
      No competing interests declared. No funding was obtained for this study.

PMID- 26202915
TI  - Transforming growth factor-beta1 up-regulates connexin43 expression in human
      granulosa cells.
AB  - STUDY QUESTION: Does transforming growth factor-beta1 (TGF-beta1) up-regulate
      connexin43 (Cx43) to promote cell-cell communication in human granulosa cells?
      SUMMARY ANSWER: TGF-beta1 up-regulates Cx43 and increases gap junction
      intercellular communication activities (GJIC) in human granulosa cells, and this
      effect occurs via the activin receptor-like kinase (ALK)5-mediated Sma- and Mad
      related protein (SMAD)2/3-SMAD4-dependent pathway. WHAT IS KNOWN ALREADY: TGF
      beta1 and its receptors are expressed in human granulosa cells, and follicular
      fluid contains TGF-beta1 protein. In human granulosa cells, Cx43 gap junctions
      play an important role in the development of follicles and oocytes. STUDY DESIGN,
      SIZE, DURATION: This is an experimental study which was performed over a 1-year
      period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immortalized human granulosa
      cells (SVOG cells) and primary human granulosa-lutein cells obtained from women
      undergoing IVF in an academic research center were used as the study models. Cx43
      mRNA and protein expression levels were examined after exposure of SVOG cells to
      recombinant human TGF-beta1. An activin/TGF-beta type I receptor inhibitor,
      SB431542, and small interfering RNAs targeting ALK4, ALK5, SMAD2, SMAD3 and SMAD4
      were used to verify the specificity of the effects and to investigate the
      molecular mechanisms. Real-time-quantitative PCR and western blot analysis were
      used to detect the specific mRNA and protein levels, respectively. GJIC between
      SVOG cells were evaluated using a scrape loading and dye transfer assay. Results
      were analyzed by one-way analysis of variance. MAIN RESULTS AND THE ROLE OF
      CHANCE: TGF-beta1 treatment increased phosphorylation of SMAD2/3 (P < 0.0001) and
      up-regulated Cx43 mRNA and protein levels (P < 0.001) in SVOG cells and these
      stimulatory effects were abolished by the TGF-beta type I receptor inhibitor
      SB431542. In addition, the up-regulatory effect of TGF-beta1 on Cx43 expression
      (mRNA and protein) was confirmed in primary cultures of human granulosa-lutein
      cells (P < 0.05). The small interfering RNA-mediated knockdown of ALK5, but not
      ALK4, abolished the TGF-beta1-induced phosphorylation of SMAD2/3 and the up
      regulation of Cx43. Furthermore, knockdown of SMAD2/3 or the common SMAD, SMAD4,
      abolished the stimulatory effects of TGF-beta1 on Cx43 expression in SVOG cells.
      The TGF-beta1-induced up-regulation of Cx43 contributed to the increase of GJIC
      between SVOG cells (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The results of
      this study were generated from in vitro system and may not reflect the intra
      ovarian microenvironment in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Our studies
      represent the first comprehensive research of molecular mechanisms of TGF-beta1
      in the regulation of Cx43 expression and GJIC in human granulosa cells and
      demonstrate that TGF-beta1 may play a crucial role in the local modulation of
      cell-cell communication. Deepening our understanding of the molecular
      determinants will offer important insights into ovarian physiology and lead to
      the development of potential therapeutic methods for fertility regulation. STUDY
      FUNDING/COMPETING INTERESTS: This research was supported by an operating grant
      from the Canadian Institutes of Health Research to P.C.K.L. There are no
      conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NA.

PMID- 26202917
TI  - Risk of ectopic pregnancy lowest with transfer of single frozen blastocyst.
AB  - STUDY QUESTION: What type of transferred embryo is associated with a lower rate
      of ectopic pregnancy? SUMMARY ANSWER: The lowest risk of ectopic pregnancy was
      associated with the transfer of blastocyst, frozen and single embryo compared
      with cleavage stage, fresh and multiple embryos. WHAT IS KNOWN ALREADY: Ectopic
      pregnancy is a recognized complication following assisted reproductive technology
      (ART) treatment. It has been estimated that the rate of ectopic pregnancy is
      doubled in pregnancies following ART treatment compared with spontaneous
      pregnancies. However, it was not clear whether the excess rate of ectopic
      pregnancy following ART treatment is related to the underlying demographic
      factors of women undergoing ART treatment, the number of embryos transferred or
      the developmental stage of the embryo. STUDY DESIGN, SIZE, DURATION: A population
      based cohort study of pregnancies following autologous treatment cycles between
      January 2009 and December 2011 were obtained from the Australian and New Zealand
      Assisted Reproduction Technology Database (ANZARD). The ANZARD collects ART
      treatment information and clinical outcomes annually from all fertility centres
      in Australia and New Zealand. PARTICIPANTS/MATERIALS, SETTING, METHODS: Between
      2009 and 2011, a total of 44 102 pregnancies were included in the analysis. The
      rate of ectopic pregnancy was compared by demographic and ART treatment factors.
      Generalized linear regression of Poisson distribution was used to estimate the
      likelihood of ectopic pregnancy. Odds ratios, adjusted odds ratios (AOR) and 95%
      confidence intervals (CI) were calculated. MAIN RESULTS AND THE ROLE OF CHANCE:
      The overall rate of ectopic pregnancy was 1.4% for women following ART treatment
      in Australia and New Zealand. Pregnancies following single embryo transfers had
      1.2% ectopic pregnancies, significantly lower than double embryo transfers (1.8%)
      (P < 0.01). The highest ectopic pregnancy rate was 1.9% for pregnancies from
      transfers of fresh cleavage embryo, followed by transfers of frozen cleavage
      embryo (1.7%), transfers of fresh blastocyst (1.3%), and transfers of frozen
      blastocyst (0.8%). Compared with fresh blastocyst transfer, the likelihood of
      ectopic pregnancy was 30% higher for fresh cleavage stage embryo transfers (AOR
      1.30, 95% CI 1.07-1.59) and was consistent across subfertility groups. Transfer
      of frozen blastocyst was associated with a significantly decreased risk of
      ectopic pregnancy (AOR 0.70, 95% CI 0.54-0.91) compared with transfer of fresh
      blastocyst. LIMITATIONS, REASON FOR CAUTION: A limitation of this population
      based study is the lack of information available on clinical- specific protocols
      and processes for embryo transfer (i.e. embryo quality, cryopreservation
      protocol, transfer techniques, etc.) and the potential impact on outcomes. WIDER
      IMPLICATIONS OF THE FINDINGS: The lowest risk of ectopic pregnancy was associated
      with the transfer of a single frozen blastocyst. This finding adds to the
      increasing evidence of better perinatal outcomes following frozen embryo
      transfers. The approach of freezing all embryos in the initiated fresh cycle and
      transfer of a single frozen blastocyst in the subsequent thaw cycle may improve
      the overall pregnancy and birth outcomes following ART treatment, in part by
      reducing the ectopic pregnancy rate. STUDY FUNDING/COMPETING INTERESTS: There is
      no funding for this study. Authors declared no competing interest related to this
      study.

PMID- 26202919
TI  - Let's not forget that many prepubertal girls do have other options besides
      ovarian tissue cryopreservation.

PMID- 26202918
TI  - Effects of antifreeze proteins on the vitrification of mouse oocytes: comparison
      of three different antifreeze proteins.
AB  - STUDY QUESTION: Can antifreeze proteins (AFPs) from three different sources
      improve the efficacy of mouse oocyte vitrification? SUMMARY ANSWER: Treatment
      with AFPs can improve both murine oocyte quality and embryo development, and
      reduce reactive oxygen species (ROS) production in vitrified-warmed oocytes. WHAT
      IS KNOWN ALREADY: A previous study discovered that vitrification of immature
      oocytes and 2-cell stage embryos of mice augmented with antifreeze glycoproteins
      at 40 mg/ml dramatically improved the morphological integrity of the samples,
      suggesting that AFPs have the ability to inhibit ice formation and stabilize the
      plasma membrane. STUDY DESIGN, SIZE, DURATION: Metaphase II oocytes were obtained
      from 4-week-old BD-F1 mice. AFPs from bacteria (Flavobacterium frigoris ice
      binding protein (FfIBP)), yeast (Glaciozyma sp. ice-binding protein (LeIBP)) and
      fish (Type III AFP) were added to the vitrification and warming solutions
      individually. Survival and development, meiotic spindle organization,
      intracellular ROS, mitochondrial activity, DNA double-strand breaks (DSBs) and
      repair of damaged DNA were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Vitrification of oocytes was performed with the CryoTop (equilibration solution:
      7.5% ethylene glycol (EG) and 7.5% 1,2-propandiol (PROH) for 5 min; vitrification
      solution: 15% EG, 15% PROH and 0.5 M sucrose for 1 min). Warming was performed in
      three steps with decreasing concentrations of sucrose (1.0, 0.5 and 0.25 M
      sucrose). MAIN RESULTS AND THE ROLE OF CHANCE: AFP treatment can improve murine
      oocyte quality and embryo development. Survival rates, cleavage rates and
      blastocyst rates (blastocyst per cleaved and per survived oocytes) of oocytes in
      AFP-treated groups were significantly higher than those in the control group
      [75.0, 89.0, 90.0 and 85.0% for survival rate (P = 0.012); 58.7, 89.0, 87.8 and
      81.2% for cleavage rate (P = 0.003); 52.3, 87.7, 78.5 and 76.8% for blastocyst
      per cleaved oocytes (P < 0.01); 30.7, 78.0, 68.9 and 62.4% for blastocyst per
      survived oocytes (P < 0.01) in control, FfIBP, LeIBP and Type III AFP-treated
      groups, respectively]. The mean (+/-SD) number of apoptotic blastomeres per
      blastocyst was significantly lower in AFP-treated groups than in the control
      group (9.1 +/- 1.0, 2.0 +/- 1.7, 2.3 +/- 1.2 and 2.7 +/- 2.4 in control, FfIBP,
      LeIBP and Type III AFP-treated groups, respectively, P = 0.040). FfIBP treatment
      was the most effective in maintaining normal meiotic spindle organization and
      chromosome alignment (52.0, 92.0, 80.0 and 83.0% in control, FfIBP, LeIBP and
      Type III AFP-treated groups, respectively, P < 0.01). Intracellular ROS levels
      (mean +/- SD) significantly decreased in the AFP-treated groups (17.0 +/- 11.2,
      8.4 +/- 8.2, 10.3 +/- 6.4 and 11.6 +/- 12.3 in control, FfIBP, LeIBP and Type III
      AFP-treated groups, respectively, P < 0.01), and the FfIBP and LeIBP groups had
      significantly lower DNA DSBs, compared with controls (65.2, 30.8, 44.4 and 55.8%
      in control, FfIBP, LeIBP and Type III AFP-treated groups, respectively, P <
      0.01). LIMITATIONS, REASONS FOR CAUTION: The origins of FfIBP and LeIBP were
      bacteria and yeast, respectively. Therefore, treatment of human oocytes and
      embryos with these AFPs should be tested before clinical application. WIDER
      IMPLICATIONS OF THE FINDINGS: After further research, AFPs can potentially be
      applied to human oocyte cryopreservation to improve the efficacy of
      vitrification. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a
      grant of the Korea Healthcare technology R&D Project, Ministry of Health &
      Welfare, Republic of Korea (HI12C0055). The authors have no conflict of interest
      to declare.

PMID- 26202920
TI  - Preliminary trials of a specific gravity technique in the determination of early
      embryo growth potential?.
AB  - STUDY QUESTION: Can a modified specific gravity technique be used to distinguish
      viable from nonviable embryos? SUMMARY ANSWER: Preliminary data suggests a
      modified specific gravity technique can be used to determine embryo viability and
      potential for future development. WHAT IS KNOWN ALREADY: Single embryo transfer
      (SET) is fast becoming the standard of practice. However, there is currently no
      reliable method to ensure development of the embryo transferred. STUDY DESIGN,
      SIZE, DURATION: A preliminary, animal-based in vitro study of specific gravity as
      a predictor of embryo development using a mouse model. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: After a brief study to demonstrate embryo recovery, experiments
      were conducted to assess the ability of the specific gravity system (SGS) to
      distinguish between viable and nonviable embryos. In the first study, 1-cell
      mouse embryos were exposed to the SGS with or without previous exposure to an
      extreme heat source (60 degrees C); measurements were repeated daily for 5 days.
      In the second experiment, larger pools of 1-cell embryos were either placed
      directly in culture or passed through the SGS and then placed in culture and
      monitored for 4 days. MAIN RESULTS AND THE ROLE OF CHANCE: In the first
      experiment, viable embryos demonstrated a predictable pattern of descent time
      over the first 48 h of development (similar to previous experience with the SGS),
      while embryos that were heat killed demonstrated significantly altered drop
      patterns (P < 0.001); first descending faster. In the second experiment, average
      descent times were different for embryos that stalled early versus those that
      developed to blastocyst (P < 0.001). Interestingly, more embryos dropped through
      the SGS developed to blastocyst than the culture control (P < 0.01). LIMITATIONS,
      REASONS FOR CAUTION: As this is a preliminary report of the SGS technology
      determining viability, a larger embryo population will be needed. Further, the
      current in vitro study will need to be followed by fecundity studies prior to
      application to a human population. WIDER IMPLICATIONS OF THE FINDINGS: If proven,
      the SGS would provide a noninvasive means of assessing embryos prior to transfer
      after assisted reproductive technologies procedures, thereby improving fecundity
      and allowing more reliable SET. STUDY FUNDING/COMPETING INTERESTS: The authors
      gratefully acknowledge the funding support of the U.S. Jersey Association, the
      Laura W. Bush Institute for Women's Health and a Howard Hughes Medical Institute
      grant through the Undergraduate Science Education Program to Texas Tech
      University. None of the authors have any conflict of interest regarding this
      work. TRIAL REGISTRATION NUMBER: none.

PMID- 26202921
TI  - Saturated fatty acids enhance TLR4 immune pathways in human trophoblasts.
AB  - STUDY QUESTION: What are the effects of fatty acids on placental inflammatory
      cytokine with respect to toll-like receptor-4/nuclear factor-kappa B (TLR4/NF
      kB)? SUMMARY ANSWER: Exogenous fatty acids induce a pro-inflammatory cytokine
      response in human placental cells in vitro via activation of TLR4 signaling
      pathways. WHAT IS KNOWN ALREADY: The placenta is exposed to changes in
      circulating maternal fatty acid concentrations throughout pregnancy. Fatty acids
      are master regulators of innate immune pathways through recruitment of toll-like
      receptors and activation of cytokine synthesis. STUDY DESIGN, SIZE, DURATION:
      Trophoblast cells isolated from 14 normal term human placentas were incubated
      with long chain fatty acids (FA) of different carbon length and degree of
      saturation. The expression and secretion of interleukin-6 (IL-6), IL-8 and tumor
      necrosis factor-alpha (TNF-alpha) were measured by reverse transcription
      polymerase chain reaction and enzyme-linked immunosorbent assay. Antibodies
      against TLR4 ligand binding domain, downstream signaling and anti-p65 NFkB
      inhibitor were used to characterize the pathways of FA action.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: General approach used primary human
      term trophoblast cell culture. Methods and end-points used real-time quantitative
      PCR, cytokine measurements, immunohistochemistry, western blots. MAIN RESULTS AND
      THE ROLE OF CHANCE: The long chain saturated fatty acids, stearic and palmitic
      (PA), stimulated the synthesis as well as the release of TNF-alpha, IL-6 and IL-8
      by trophoblast cells (2- to 6-fold, P < 0.001). In contrast, the unsaturated
      (palmitoleic, oleic, linoleic) acids did not modify cytokine expression
      significantly. Palmitate-induced inflammatory effects were mediated via TLR4
      activation, NF-kB phosphorylation and nuclear translocation. LIMITATIONS, REASONS
      FOR CAUTION: TNF-alpha protein level was close to the limit of detection in the
      culture medium even when cells were cultured with PA. WIDER IMPLICATIONS OF THE
      FINDINGS: These mechanisms open the way to a better understanding of how changes
      in maternal lipid homeostasis may regulate placental inflammatory status. STUDY
      FUNDING/COMPETING INTERESTS: X.Y. was recipient of fellowship award from West
      China Second University Hospital, Sichuan University (NIH HD 22965-19). The
      authors have nothing else to disclose. TRIAL REGISTRATION NUMBER: None.

PMID- 26202923
TI  - Screening for dysglycaemia by oral glucose tolerance test should be recommended
      in all women with polycystic ovary syndrome.
AB  - STUDY QUESTION: Should fasting glucose (FG) or an oral glucose tolerance test
      (OGTT) be used to screen for dysglycaemia in women with polycystic ovary syndrome
      (PCOS)? SUMMARY ANSWER: A full OGTT should be recommended as the screening method
      for dysglycaemia in women with PCOS, regardless of BMI or family history of
      diabetes mellitus (DM). STUDY DESIGN, SIZE, DURATION: A cross-sectional study on
      467 Chinese women diagnosed with PCOS by the Rotterdam criteria between January
      2010 to December 2013. PARTICIPANTS, SETTING, METHODS: The study was done at a
      university hospital in Hong Kong. All subjects underwent a 75 g OGTT after
      overnight fasting. We evaluated the performance of FG alone, when compared with
      the full OGTT, in identifying subjects with dysglycaemia (prediabetes or DM,
      according to the 2010 diagnostic criteria of the American Diabetes Association).
      MAIN RESULTS AND THE ROLE OF CHANCE: Of the 467 subjects, 58 (12.4%) had
      dysglycaemia, among which 46 (9.8%) had prediabetes and 12 (2.6%) had DM,
      including 4 with known DM. Of the 46 subjects with prediabetes, 25 (54.3%) had
      normal FG and of the 8 subjects with screened DM in this study, 1 (12.5%) had
      normal FG. The sensitivity of FG alone in screening for prediabetes, DM and
      overall dysglycaemia were 45.7, 87.5 and 48.1%, respectively, i.e. missing 54.3%
      of prediabetes and 12.5% of DM cases as defined by the OGTT. Among the 54
      subjects with screened dysglycaemia, 20 (37.0%) had BMI < 25 kg/m(2) and 35
      (64.8%) had no family history of DM. LIMITATIONS, REASONS FOR CAUTION: We only
      reported on the biochemical diagnosis of DM based on a single time point. In
      clinical practice, confirmatory results at another time point is required for
      definitive diagnosis in asymptomatic subjects. WIDER IMPLICATIONS OF THE
      FINDINGS: There is an ongoing debate as to whether FG or an OGTT should be used
      as a screening method for dysglycaemia in women with PCOS. Some guidelines also
      recommend glucose screening only in those who are overweight and/or having family
      history of diabetes (DM). There have been scarce data on this issue in the
      Chinese population, which the current study aims at addressing. STUDY
      FUNDING/COMPETING INTERESTS: The study was supported by a research grant from the
      Hong Kong Obstetrical and Gynaecological Trust Fund, as well as internal research
      funding of the Department of Obstetrics and Gynaecology, The University of Hong
      Kong. All authors have no competing interests.

PMID- 26202924
TI  - Differences in gene expression profiles between human preimplantation embryos
      cultured in two different IVF culture media.
AB  - STUDY QUESTION: Is gene expression in human preimplantation embryos affected by
      the medium used for embryo culture in vitro during an IVF treatment? SUMMARY
      ANSWER: Six days of in vitro culture of human preimplantation embryos resulted in
      medium-dependent differences in expression level of genes involved in apoptosis,
      protein degradation, metabolism and cell-cycle regulation. WHAT IS KNOWN ALREADY:
      Several human studies have shown an effect of culture medium on embryo
      development, pregnancy outcome and birthweight. However, the underlying
      mechanisms in human embryos are still unknown. In animal models of human
      development, it has been demonstrated that culture of preimplantation embryos in
      vitro affects gene expression. In humans, it has been found that culture medium
      affects gene expression of cryopreserved embryos that, after thawing, were
      cultured in two different media for 2 more days. STUDY DESIGN, SIZE, DURATION: In
      a multicenter trial, women were randomly assigned to two culture medium groups
      [G5 and human tubal fluid (HTF)]. Data on embryonic development were collected
      for all embryos. In one center, embryos originating from two pronuclei (2PN)
      zygotes that were not selected for transfer or cryopreservation on Day 2 or 3
      because of lower morphological quality, were cultured until Day 6 and used in
      this study, if couples consented. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ten
      blastocysts each from the G5 and HTF study groups, matched for fertilization
      method, maternal age and blastocyst quality, were selected and their mRNA was
      isolated and amplified. Embryos were examined individually for genome-wide gene
      expression using Agilent microarrays and PathVisio was used to identify the
      pathways that showed a culture medium-dependent activity. MAIN RESULTS AND THE
      ROLE OF CHANCE: Expression of 951 genes differed significantly (P < 0.01) between
      the G5 and HTF groups. Eighteen pathways, involved in apoptosis, metabolism,
      protein processing and cell-cycle regulation, showed a significant
      overrepresentation of differentially expressed genes. The DNA replication, G1 to
      S cell-cycle control and oxidative phosphorylation pathways were up-regulated in
      the G5 group compared with the HTF group. This is in agreement with the
      morphological assessment of the 1527 embryos (originating from 2PN zygotes),
      which showed that embryos consisted of more cells on Day 2 (3.73 +/- 1.30 versus
      3.40 +/- 1.35, P < 0.001) and Day 3 (7.00 +/- 2.41 versus 5.84 +/- 2.36, P <
      0.001) in the G5 group when compared with the HTF group. Furthermore, the
      implantation rate was significantly higher in the G5 group compared with the HTF
      group (26.7% versus 14.7%, P = 0.002) after transfer on the second or the third
      day after fertilization. LIMITATIONS, REASONS FOR CAUTION: Despite careful
      matching of the embryos, it cannot be excluded that the differences observed
      between the study groups are caused by factors that we did not investigate.
      Extrapolation of these results to embryos used for transfer demands caution as in
      the present study embryos that were not selected for either embryo transfer or
      cryopreservation have been used for the culture experiment until Day 6. WIDER
      IMPLICATIONS OF THE FINDINGS: This study shows that gene expression in human
      preimplantation embryos is altered by the culture medium used during IVF
      treatment and provides insight into the biological pathways that are affected.
      Whether these changes in gene expression have any long-term effects on children
      born after IVF remains unknown. However, it is possible that early adaptations of
      the preimplantation embryo to its environment persist during fetal and post-natal
      development. STUDY FUNDING/COMPETING INTERESTS: No funding and no competing
      interests declared. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 26202922
TI  - Identification and replication of prediction models for ovulation, pregnancy and
      live birth in infertile women with polycystic ovary syndrome.
AB  - STUDY QUESTION: Can we build and validate predictive models for ovulation and
      pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS)?
      SUMMARY ANSWER: We were able to develop and validate a predictive model for
      pregnancy outcomes in women with PCOS using simple clinical and biochemical
      criteria particularly duration of attempting conception, which was the most
      consistent predictor among all considered factors for pregnancy outcomes. WHAT IS
      KNOWN ALREADY: Predictive models for ovulation and pregnancy outcomes in
      infertile women with polycystic ovary syndrome have been reported, but such
      models require validation. STUDY DESIGN, SIZE, AND DURATION: This is a secondary
      analysis of the data from the Pregnancy in Polycystic Ovary Syndrome I and II
      (PPCOS-I and -II) trials. Both trials were double-blind, randomized clinical
      trials that included 626 and 750 infertile women with PCOS, respectively. PPCOS-I
      participants were randomized to either clomiphene citrate (CC), metformin, or
      their combination, and PPCOS-II participants to either letrozole or CC for up to
      five treatment cycles. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: Linear
      logistic regression models were fitted using treatment, BMI, and other published
      variables as predictors of ovulation, conception, clinical pregnancy, and live
      birth as the outcome one at a time. We first evaluated previously reported
      significant predictors, and then constructed new prediction models. Receiver
      operating characteristic (ROC) curves were constructed and the area under the
      curves (AUCs) was calculated to compare performance using different models and
      data. Chi-square tests were used to examine the goodness-of-fit and prediction
      power of logistic regression model. MAIN RESULTS AND THE ROLE OF CHANCE:
      Predictive factors were similar between PPCOS-I and II, but the two participant
      samples differed statistically significantly but the differences were clinically
      minor on key baseline characteristics and hormone levels. Women in PPCOS-II had
      an overall more severe PCOS phenotype than women in PPCOS-I. The clinically minor
      but statistically significant differences may be due to the large sample sizes.
      Younger age, lower baseline free androgen index and insulin, shorter duration of
      attempting conception, and higher baseline sex hormone-binding globulin
      significantly predicted at least one pregnancy outcome. The ROC curves (with AUCs
      of 0.66-0.76) and calibration plots and chi-square tests indicated stable
      predictive power of the identified variables (P-values >=0.07 for all goodness-of
      fit and validation tests). LIMITATIONS, REASONS FOR CAUTION: This is a secondary
      analysis. Although our primary objective was to confirm previously reported
      results and identify new predictors of ovulation and pregnancy outcomes among
      PPCOS-II participants, our approach is exploratory and warrants further
      replication. WIDER IMPLICATIONS OF THE FINDINGS: We have largely confirmed the
      predictors that were identified in the PPCOS-I trial. However, we have also
      revealed new predictors, particularly the role of smoking. While a history of
      ever smoking was not a significant predictor for live birth, a closer look at
      current, quit, and never smoking revealed that current smoking was a significant
      risk factor. STUDY FUNDING/COMPETING INTERESTS: The Eunice Kennedy Shriver
      National Institute of Child Health and Human Development (NICHD) Grants U10
      HD27049, U10 HD38992, U10HD055925, U10 HD39005, U10 HD33172, U10 HD38998, U10
      HD055936, U10 HD055942, and U10 HD055944; and U54-HD29834. Heilongjiang
      University of Chinese Medicine Grants 051277 and B201005. R.S.L. reports
      receiving consulting fees from Euroscreen, AstraZeneca, Clarus Therapeutics, and
      Takeda, and grant support from Ferring, Astra Zeneca, and Toba. K.R.H. reports
      receiving grant support from Roche Diagnostics and Ferring Pharmascience. G.C.
      reports receiving Honorarium and grant support from Abbvie Pharmaceuticals and
      Bayer Pharmaceuticals. M.P.D. holds equity from Advanced Reproductive Care Inc.
      and DS Biotech, receives fees from Advanced Reproductive Care Inc., Actamax,
      Auxogyn, ZSX Medical, Halt Medical, and Neomed, and receives grant support from
      Boehringer-Ingelheim, Abbott, and BioSante, Ferring Pharmaceuticals, and EMD
      Serono. H.Z. receives research support from the Chinese 1000-scholar plan. Others
      report no disclosures other than NIH grant support. TRIAL REGISTRATION NUMBER:
      PPCOS-I and -II were respectively registered at Clinicaltrials.gov: NCT00719186
      and NCT00719186.

PMID- 26202925
TI  - Independent development of lymphoid and histiocytic malignancies from a shared
      early precursor.

PMID- 26202926
TI  - Tumor-associated macrophages and extracellular matrix metalloproteinase inducer
      in prognosis of multiple myeloma.

PMID- 26202927
TI  - Molecular characterization of acute erythroid leukemia (M6-AML) using targeted
      next-generation sequencing.

PMID- 26202928
TI  - Metabolic plasticity in CLL: adaptation to the hypoxic niche.
AB  - Metabolic transformation in cancer is increasingly well understood. However,
      little is known about the metabolic responses of cancer cells that permit their
      survival in different microenvironments. We have used a nuclear magnetic
      resonance based approach to monitor metabolism in living primary chronic lymphoid
      leukemia (CLL) cells and to interrogate their real-time metabolic responses to
      hypoxia. Our studies demonstrate considerable metabolic plasticity in CLL cells.
      Despite being in oxygenated blood, circulating CLL cells are primed for hypoxia
      as measured by constitutively low level hypoxia-inducible factor (HIF-1alpha)
      activity and modest lactate production from glycolysis. Upon entry to hypoxia we
      observed rapid upregulation of metabolic rates. CLL cells that had adapted to
      hypoxia returned to the 'primed' state when re-oxygenated and again showed the
      same adaptive response upon secondary exposure to hypoxia. We also observed HIF
      1alpha independent differential utilization of pyruvate in oxygenated and hypoxic
      conditions. When oxygenated, CLL cells released pyruvate, but in hypoxia imported
      pyruvate to protect against hypoxia-associated oxidative stress. Finally, we
      identified a marked association of slower resting glucose and glutamine
      consumption, and lower alanine and lactate production with Binet A0 stage samples
      indicating that CLL may be divided into tumors with higher and lower metabolic
      states that reflect disease stage. 

PMID- 26202929
TI  - A new monoclonal antibody (CAL2) detects CALRETICULIN mutations in formalin-fixed
      and paraffin-embedded bone marrow biopsies.
AB  - Recent advances in the diagnostic of myeloproliferative neoplasms (MPNs)
      discovered CALRETICULIN (CALR) mutations as a major driver in these disorders. In
      contrast to JAK2 mutations being mainly associated with polycythaemia vera, CALR
      mutations are only associated with primary myelofibrosis (PMF) and essential
      thrombocythaemia (ET). CALR mutations are present in the majority of PMF and ET
      patients lacking JAK2 and MPL mutations. As these CALR mutations are absent from
      reactive bone marrow (BM) lesions their presence indicates ET or PMF. So far
      these mutations are detectable only by molecular assays. Their molecular
      detection is cumbersome because of the great CALR mutation heterogeneity.
      Therefore, the availability of a simple assay would be of great help. All CALR
      mutations reported lead to a frameshift generating a new 36 amino-acid C
      terminus. We generated a monoclonal antibody (CAL2) to this C-neoterminus by
      immunizing mice with a representative peptide and compared its performance with
      Sanger sequencing data in 173 MPNs and other BM diseases. There was a 100%
      correlation between the molecular and the CAL2 immunohistochemical (IHC) assays.
      Thus, the detection of CALR mutations by the CAL2 IHC is a specific, sensitive,
      rapid, simple and low-cost method. 

PMID- 26202930
TI  - TRIB2 reinforces the oncogenic transcriptional program controlled by the TAL1
      complex in T-cell acute lymphoblastic leukemia.

PMID- 26202931
TI  - Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute
      lymphoblastic leukemia: an international collaborative study.
AB  - Deletions in IKZF1 are found in ~15% of children with B-cell precursor acute
      lymphoblastic leukemia (BCP-ALL). There is strong evidence for the poor prognosis
      of IKZF1 deletions affecting exons 4-7 and exons 1-8, but evidence for the
      remaining 33% of cases harboring other variants of IKZF1 deletions is lacking. In
      an international multicenter study we analyzed the prognostic value of these rare
      variants in a case-control design. Each IKZF1-deleted case was matched to three
      IKZF1 wild-type controls based on cytogenetic subtype, treatment protocol, risk
      stratification arm, white blood cell count and age. Hazard ratios for the
      prognostic impact of rare IKZF1 deletions on event-free survival were calculated
      by matched pair Cox regression. Matched pair analysis for all 134 cases with rare
      IKZF1 deletions together revealed a poor prognosis (P<0.001) that was evident in
      each risk stratification arm. Rare variant types with the most unfavorable event
      free survival were DEL 2-7 (P=0.03), DEL 2-8 (P=0.002) and DEL-Other (P<0.001).
      The prognosis of each type of rare variant was equal or worse compared with the
      well-known major DEL 4-7 and DEL 1-8 IKZF1 deletion variants. We therefore
      conclude that all variants of rare IKZF1 deletions are associated with an
      unfavorable prognosis in pediatric BCP-ALL. 

PMID- 26202932
TI  - Adoptive B-cell transfer mouse model of human myeloma.

PMID- 26202933
TI  - Activation of OCT4 enhances ex vivo expansion of human cord blood hematopoietic
      stem and progenitor cells by regulating HOXB4 expression.
AB  - Although hematopoietic stem cells (HSC) are the best characterized and the most
      clinically used adult stem cells, efforts are still needed to understand how to
      best ex vivo expand these cells. Here we present our unexpected finding that OCT4
      is involved in the enhancement of cytokine-induced expansion capabilities of
      human cord blood (CB) HSC. Activation of OCT4 by Oct4-activating compound 1
      (OAC1) in CB CD34(+) cells enhanced ex vivo expansion of HSC, as determined by a
      rigorously defined set of markers for human HSC, and in vivo short-term and long
      term repopulating ability in NSG mice. Limiting dilution analysis revealed that
      OAC1 treatment resulted in 3.5-fold increase in the number of SCID repopulating
      cells (SRCs) compared with that in day 0 uncultured CD34(+) cells and 6.3-fold
      increase compared with that in cells treated with control vehicle. Hematopoietic
      progenitor cells, as assessed by in vitro colony formation, were also enhanced.
      Furthermore, we showed that OAC1 treatment led to OCT4-mediated upregulation of
      HOXB4. Consistently, siRNA-mediated knockdown of HOXB4 expression suppressed
      effects of OAC1 on ex vivo expansion of HSC. Our study has identified the OCT4
      HOXB4 axis in ex vivo expansion of human CB HSC. 

PMID- 26202934
TI  - beta-Catenin is required for intrinsic but not extrinsic BCR-ABL1 kinase
      independent resistance to tyrosine kinase inhibitors in chronic myeloid leukemia.
AB  - Activation of nuclear beta-catenin and expression of its transcriptional targets
      promotes chronic myeloid leukemia (CML) progression, tyrosine kinase inhibitor
      (TKI) resistance, and leukemic stem cell self-renewal. We report that nuclear
      beta-catenin has a role in leukemia cell-intrinsic but not -extrinsic BCR-ABL1
      kinase-independent TKI resistance. Upon imatinib inhibition of BCR-ABL1 kinase
      activity, beta-catenin expression was maintained in intrinsically resistant cells
      grown in suspension culture and sensitive cells cultured in direct contact (DC)
      with bone marrow (BM) stromal cells. Thus, TKI resistance uncouples beta-catenin
      expression from BCR-ABL1 kinase activity. In beta-catenin reporter assays,
      intrinsically resistant cells showed increased transcriptional activity versus
      parental TKI-sensitive controls, and this was associated with restored expression
      of beta-catenin target genes. In contrast, DC with BM stromal cells promoted TKI
      resistance, but had little effects on Lef/Tcf reporter activity and no consistent
      effects on cytoplasmic beta-catenin levels, arguing against a role for beta
      catenin in extrinsic TKI resistance. N-cadherin or H-cadherin blocking antibodies
      abrogated DC-based resistance despite increasing Lef/Tcf reporter activity,
      suggesting that factors other than beta-catenin contribute to extrinsic, BM
      derived TKI resistance. Our data indicate that, while nuclear beta-catenin
      enhances survival of intrinsically TKI-resistant CML progenitors, it is not
      required for extrinsic resistance mediated by the BM microenvironment. 

PMID- 26202935
TI  - Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against
      AML-initiating cells engrafted into immunosuppressed NSG mice.
AB  - Currently available combination chemotherapy for acute myeloid leukemia (AML)
      often fails to result in long-term remissions, emphasizing the need for novel
      therapeutic strategies. We reasoned that targeted inhibition of a prominent
      nuclear exporter, XPO1/CRM1, could eradicate self-renewing leukemia-initiating
      cells (LICs) whose survival depends on timely XPO1-mediated transport of specific
      protein and RNA cargoes. Using an immunosuppressed mouse model bearing primary
      patient-derived AML cells, we demonstrate that selinexor (KPT-330), an oral
      antagonist of XPO1 that is currently in clinical trials, has strong activity
      against primary AML cells while sparing normal stem and progenitor cells.
      Importantly, limiting dilution transplantation assays showed that this cytotoxic
      activity is not limited to the rapidly proliferating bulk population of leukemic
      cells but extends to the LICs, whose inherent drug resistance and unrestricted
      self-renewal capacity has been implicated in the difficulty of curing AML
      patients with conventional chemotherapy alone. 

PMID- 26202936
TI  - Flow cytometric measurement of respiratory burst activity and surface expression
      of neutrophils for septic patient prognosis.
AB  - BACKGROUND: The hyperinflammation that begins with sepsis is essential for
      eradicating infection but also causes hypoperfusion and organ failure. To
      understand the innate immune status of septic patients, the functional and
      phenotypic changes of neutrophils during sepsis and their clinical implication
      were studied. METHODS: Seventy-four patients who were admitted to intensive care
      unit due to severe sepsis or septic shock were enrolled. Surface antigens of
      neutrophils (CD64, CD10, and CD16) were detected by flow cytometry. Respiratory
      burst activity (RBA) was measured by flow cytometry using 2',7'
      dichlorofluorescein diacetate and phorbol-12-myristate-13-acetate. The parameters
      were serially examined at Days 1 and 8 in septic shock patients. RESULTS: High
      CD64 and low CD10 and CD16 on Day 1 was associated with sepsis severity (P =
      0.003, 0.017, and 0.007, respectively). On Day 1, RBA and CD64 were higher in
      survivors than in nonsurvivors of septic shock patients (P = 0.012 and 0.027,
      respectively), and on Day 8, CD10 and CD16 were higher in survivors than in
      nonsurvivors (P = 0.019 and 0.036, respectively). High RBA and high CD64 on Day 1
      showed low 28-day mortality in univariate analysis (P = 0.018 and 0.034,
      respectively). In multivariate analysis, RBA maintained statistical significance
      (P = 0.042) but CD64 revealed only a tendency (P = 0.064). CONCLUSIONS:
      Neutrophil surface antigen (CD64, CD10, and CD16) could reflect sepsis severity.
      High CD64 expression and high RBA at early phase of sepsis might be associated
      with better prognosis, whereas high expression of CD10 and CD16 at late phase of
      sepsis might be associated with better prognosis. (c) 2015 International Clinical
      Cytometry Society.

PMID- 26202937
TI  - Expression and ontogeny of growth hormone (Gh) in the protogynous hermaphroditic
      ricefield eel (Monopterus albus).
AB  - Growth hormone (GH) is a single-chain polypeptide hormone mainly secreted by
      somatotropes of the anterior pituitary gland and is an important regulator of
      somatic growth in vertebrates including teleosts. In this study, a polyclonal
      antiserum against ricefield eel Gh was generated and the expression of Gh at the
      mRNA and protein levels was analyzed. Both RT-PCR and western blot analysis
      showed that Gh was predominantly expressed in the pituitary glands of ricefield
      eels. The immunoreactive Gh signals were localized to the multicellular layers of
      the adenohypophysis adjacent to the neurohypophysis in ricefield eels.
      Ontogenetic analysis showed that immunoreactive Gh signals could be detected in
      the pituitary glands of ricefield eel embryos as early as 3 days post
      fertilization. During the sex change from female to male, the levels of the
      immunoreactive Gh signals in the pituitary glands of the ricefield eels peaked at
      the intersexual stage. These results suggest that Gh in the pituitary glands may
      be associated with embryonic development before hatching, as well as with the sex
      change in the adult ricefield eels, possibly via the classical endocrine manner.

PMID- 26202938
TI  - Carriage of Mutant Dihydrofolate Reductase and Dihydropteroate Synthase Genes
      among Plasmodium falciparum Isolates Recovered from Pregnant Women with
      Asymptomatic Infection in Lagos, Nigeria.
AB  - OBJECTIVE: To assess N51I, C59R and S108N polymorphisms of dihydrofolate
      reductase (dhfr) and A437G and K540E of dihydropteroate synthase (dhps) genes of
      P. falciparum isolates recovered from pregnant women with asymptomatic malaria in
      a coastal setting in Nigeria. SUBJECTS AND METHODS: A total of 107 consenting and
      consecutively enrolled pregnant women (mean age +/- standard deviation, 26.6 +/-
      4.5 years) attending antenatal care at the Iru/Victoria Island Primary Health
      Centre, Lagos, were screened for peripheral malaria by microscopy, by a histidine
      rich protein-2-based rapid diagnostic test (RDT) and by polymerase chain reaction
      (PCR) using finger-pricked and dot blood samples. DNA was extracted from the
      blood and used for dhfr and dhps gene polymorphism analyses by PCR and
      restriction fragment length polymorphism. The sociodemographic and parasite data
      obtained were analysed. RESULTS: Of the 107 patients, 34 (31.8%), 46 (43%) and 40
      (37.4%) were found to be P. falciparum infected using microscopy, RDT and
      corrected RDT-PCR, respectively (p < 0.05). The prevalence of P. falciparum
      isolates with mutant and mixed genotypes of dhfr at codons 51, 59 and 108 was 70,
      75 and 80%, respectively, and the triple mutation in the homozygous form was 35%.
      The prevalence of the homozygous quintuple dhfr plus dhps mutant was 5%, while
      that of the P. falciparum isolates with mutant or mixed genotypes of dhps at
      codons 437 and 540 was 37.5 and 22.5%, respectively. CONCLUSION: This study
      revealed the emergence of the K540E mutation among the parasite population in
      Lagos. However, it supports the implementation of the intermittent preventive
      treatment of malaria during pregnancy with sulphadoxine-pyrimethamine with
      continuous effectiveness monitoring in the study area.

PMID- 26202939
TI  - Experimental evolution of the model eukaryote Saccharomyces cerevisiae yields
      insight into the molecular mechanisms underlying adaptation.
AB  - Understanding how changes in DNA drive the emergence of new phenotypes and fuel
      evolution remains a major challenge. One major hurdle is the lack of a fossil
      record of DNA that allows linking mutations to phenotypic changes. However, the
      emergence of high-throughput sequencing technologies now allows sequencing
      genomes of natural and experimentally evolved microbial populations to study how
      mutations arise and spread through a population, how new phenotypes arise and how
      this ultimately leads to adaptation. Here, we highlight key studies that have
      increased our mechanistic understanding of evolution. We specifically focus on
      the model eukaryote Saccharomyces cerevisiae because its relatively short
      replication time, much-studied biology and available molecular toolbox have made
      it a prime model for molecular evolution studies. 

PMID- 26202940
TI  - Fluorescence Polarization Switching from a Single Silicon Vacancy Colour Centre
      in Diamond.
AB  - Single-photon emitters with stable and uniform photoluminescence properties are
      important for quantum technology. However, in many cases, colour centres in
      diamond exhibit spectral diffusion and photoluminescence intensity fluctuation.
      It is therefore essential to investigate the dynamics of colour centres at the
      single defect level in order to enable the on-demand manipulation and improved
      applications in quantum technology. Here we report the polarization switching,
      intensity jumps and spectral shifting observed on a negatively charged single
      silicon-vacancy colour centre in diamond. The observed phenomena elucidate the
      single emitter dynamics induced by photoionization of nearby electron donors in
      the diamond. 

PMID- 26202941
TI  - A Structure-Activity Relationship Study of Imidazole-5-Carboxylic Acid
      Derivatives as Angiotensin II Receptor Antagonists Combining 2D and 3D QSAR
      Methods.
AB  - Two-dimensional (2D) and three-dimensional (3D) quantitative structure-activity
      relationship (QSAR) studies were performed for correlating the chemical
      composition of imidazole-5-carboxylic acid analogs and their angiotensin II
      [Formula: see text] receptor antagonist activity using partial least squares and
      k-nearest neighbor, respectively. For comparing the three different feature
      selection methods of 2D-QSAR, k-nearest neighbor models were used in conjunction
      with simulated annealing (SA), genetic algorithm and stepwise coupled with
      partial least square (PLS) showed variation in biological activity. The
      statistically significant best 2D-QSAR model having good predictive ability with
      statistical values of [Formula: see text] and [Formula: see text] was developed
      by SA-partial least square with the descriptors like [Formula: see text]count,
      5Chain count, SdsCHE-index, and H-acceptor count, showing that increase in the
      values of these descriptors is beneficial to the activity. The 3D-QSAR studies
      were performed using the SA-PLS. A leave-one-out cross-validated correlation
      coefficient [Formula: see text] and predicate activity [Formula: see text] =
      0.7226 were obtained. The information rendered by QSAR models may lead to a
      better understanding of structural requirements of substituted imidazole-5
      carboxylic acid derivatives and also aid in designing novel potent
      antihypertensive molecules. 

PMID- 26202942
TI  - Identification and Characterization of a Pesticide Degrading Flavobacterium
      Species EMBS0145 by 16S rRNA Gene Sequencing.
AB  - Organophosphates like chlorpyrifos, diazinon, or malathion have become most
      common and indisputably most toxic pest control agents that adversely affects the
      human nervous system even at low levels of exposure. Because of their relatively
      low cost and ability to be applied on a wide range of target insects and crop,
      organophosphorus pesticides account for a large share of all insecticides used in
      India, and this in turn raises severe health concerns. In this view, the present
      investigation was aimed to identify novel species of Flavobacterium bacteria
      which is bestowed with the capacity to degrade pesticides like chlorpyrifos,
      diazinon, or malathion. The bacterium was isolated from agricultural soil
      collected from Guntur District, Andhra Pradesh, India. The samples were serially
      diluted, and the aliquots were incubated for a suitable time following which the
      suspected colony was subjected to 16S rRNA gene sequencing. The sequence thus
      obtained was aligned pairwise against Flavobacterium species, which resulted in
      identification of novel species of Flavobacterium later which was named as
      EMBS0145 and sequence was deposited in GenBank with Accession Number: JN794045. 

PMID- 26202943
TI  - Comparative Pharmacophore Modeling and QSAR Studies for Structural Requirements
      of some Substituted 2-Aminopyridine Derivatives as Inhibitors of Nitric Oxide
      Synthases.
AB  - The present study is an attempt in this direction seeking for the development and
      comparison of QSAR models of substituted 2-aminopyridine derivatives as
      inhibitors of nitric oxide synthases by different feature selection methods. The
      QSAR study was carried out on V-life Molecular Design Suite software, and the
      derived best QSAR model was derived by partial component regression method. The
      statistically significant best model with high correlation coefficient ([Formula:
      see text]) was selected for further study. The model was further validated by
      means of crossed squared correlation coefficient ([Formula: see text] and
      [Formula: see text]) which shows model has good predictive ability. The best 3D
      QSAR model showed [Formula: see text] and standard error = 0.1954. The predictive
      ability of the resultant model was evaluated using a test set molecules and the
      predicted [Formula: see text] The results reveal that the acceptor, donor,
      aliphatic, and aromatic pharmacophore properties are favorable contour sites for
      both the activities. The two-dimensional and k-nearest-neighbor contour plots
      were required for further understanding of the relationship between structural
      features of substituted 2-aminopyridine derivatives and their activities which
      should be applicable to design newer potential inducible nitric oxide synthases. 

PMID- 26202944
TI  - Dr Foster goes to America.

PMID- 26202945
TI  - The pan-deacetylase inhibitor panobinostat affects angiogenesis in hepatocellular
      carcinoma models via modulation of CTGF expression.
AB  - Post-translational modifications of chromatin components are significantly
      involved in the regulation of tumor suppressor gene and oncogene expression.
      Connective tissue growth factor (CTGF) is an epigenetically regulated growth
      factor with functions in angiogenesis and cell-matrix interactions and plays a
      pivotal role in hepatocellular carcinoma (HCC). The pharmacologic inhibition of
      histone and protein deacetylases represents a new approach to interfere with
      pathways of apoptosis and angiogenesis. We investigated the effect of the pan
      deacetylase inhibitor panobinostat (LBH589) on human HCC cell lines HepG2 (p53wt)
      and Hep3B (p53null) and in a subcutaneous xenograft model and explored the
      influence on angiogenesis. Specimens were characterized by quantitative real-time
      PCR. Protein was separated for western blotting against CTGF, VEGF, VEGF receptor
      1 (VEGFR-1/FLT-1), VEGF receptor-2 (VEGFR-2/KDR), MAPK and phospho-MAPK. In vivo,
      HepG2 cells were xenografted to NMRI mice and treated with daily i.p. injections
      of 10 mg/kg panobinostat. After 1, 7 and 28 days, real-time PCR was performed.
      Immunohistochemistry and western blotting were examined after 28 days. An
      increased significant expression of CTGF was only seen after 24 h treatment with
      0.1 uM panobinostat in HepG2 cells and Hep3B cells, whereas after 72 h treatment
      CTGF expression clearly decreased. In the xenografts, treatment with panobinostat
      showed a minimal CTGF expression after 1 day and 4 weeks, respectively. In vitro
      as well as in vivo, VEGF was not affected by panobinostat treatment at any time.
      In conclusion, panobinostat influences extracellular signaling cascades via CTGF
      dependent pathways. 

PMID- 26202946
TI  - Lead-free epitaxial ferroelectric material integration on semiconducting (100) Nb
      doped SrTiO3 for low-power non-volatile memory and efficient ultraviolet ray
      detection.
AB  - We report lead-free ferroelectric based resistive switching non-volatile memory
      (NVM) devices with epitaxial (1-x)BaTiO3-xBiFeO3 (x = 0.725) (BT-BFO) film
      integrated on semiconducting (100) Nb (0.7%) doped SrTiO3 (Nb:STO) substrates.
      The piezoelectric force microscopy (PFM) measurement at room temperature
      demonstrated ferroelectricity in the BT-BFO thin film. PFM results also reveal
      the repeatable polarization inversion by poling, manifesting its potential for
      read-write operation in NVM devices. The electroforming-free and ferroelectric
      polarization coupled electrical behaviour demonstrated excellent resistive
      switching with high retention time, cyclic endurance, and low set/reset voltages.
      X-ray photoelectron spectroscopy was utilized to determine the band alignment at
      the BT-BFO and Nb:STO heterojunction, and it exhibited staggered band alignment.
      This heterojunction is found to behave as an efficient ultraviolet photo-detector
      with low rise and fall time. The architecture also demonstrates half-wave
      rectification under low and high input signal frequencies, where the output
      distortion is minimal. The results provide avenue for an electrical switch that
      can regulate the pixels in low or high frequency images. Combined this work paves
      the pathway towards designing future generation low-power ferroelectric based
      microelectronic devices by merging both electrical and photovoltaic properties of
      BT-BFO materials. 

PMID- 26202947
TI  - Aspirin Suppresses the Growth and Metastasis of Osteosarcoma through the NF
      kappaB Pathway.
AB  - PURPOSE: Aspirin has recently been reported to reduce both the incidence and the
      risk of metastasis in colon cancer. However, there is no evidence at the cellular
      levels or in the animal models for such an effect of aspirin on cancer
      metastasis. EXPERIMENTAL DESIGN: MTT assay, colony formation assay, and apoptosis
      assay were employed to analyze the effects of aspirin on the osteosarcoma cell
      viability in vitro. The NF-kappaB activity was measured by the NF-kappaB p65
      luciferase reporter. Western blotting was used to analyze the proteins in cells.
      The migration and invasion abilities of osteosarcoma cells in vitro were measured
      by the Transwell assay. Xenograft-bearing mice were used to assess the roles of
      aspirin in both tumor growth and metastasis of osteosarcoma in vivo (n = 5-8
      mice/group). An unpaired Student t test or ANOVA with the Bonferroni post hoc
      test were used for the statistical comparisons. RESULTS: Aspirin reduced cell
      viability in a dose- and time-dependent manner in osteosarcoma cell lines, and
      aspirin synergistically sensitized osteosarcoma cells to cisplatin (DDP) in vitro
      and in vivo (P < 0.001). Moreover, aspirin markedly repressed the migration and
      invasion of osteosarcoma cells in vitro (P < 0.001), and dramatically diminished
      the occurrence of osteosarcoma xenograft metastases to the lungs in vivo (P <
      0.001). Mechanistically, aspirin diminishes osteosarcoma migration, invasion, and
      metastasis through the NF-kappaB pathway. CONCLUSIONS: Aspirin suppresses both
      the growth and metastasis of osteosarcoma through the NF-kappaB pathway at the
      cellular level and in the animal models.

PMID- 26202949
TI  - "Braking" the Cycle of Resistance in Endocrine Therapy for Breast Cancer.
AB  - Endocrine resistance leads to recurrence and death from breast cancer. Animal
      models of endocrine resistance enable preclinical identification of efficacious
      therapeutic combinations and further our understanding of resistance. This
      strategy provides new insights into optimally targeting interactions between
      estrogen receptor (ESR-1) activity and the cell cycle by CDK4/6 inhibitors. See
      related article by Wardell et al., p. 5121.

PMID- 26202948
TI  - Notch Pathway Inhibition Using PF-03084014, a gamma-Secretase Inhibitor (GSI),
      Enhances the Antitumor Effect of Docetaxel in Prostate Cancer.
AB  - PURPOSE: To investigate the efficacy and mechanisms of Notch signaling inhibition
      as an adjuvant to docetaxel in castration-resistant prostate cancer (CRPC) using
      a gamma-secretase inhibitor (GSI), PF-03084014. EXPERIMENTAL DESIGN: The effect
      of PF-03084014 on response to docetaxel was evaluated in docetaxel-sensitive and
      docetaxel-resistant CRPC cell lines in vitro and in murine models. Both soft
      tissue and bone sites were evaluated in vivo. Impacts on cell proliferation,
      apoptosis, cancer stem cells, and angiogenesis were evaluated. RESULTS: The
      combination of PF-03084014 plus docetaxel reduced both docetaxel-sensitive and
      docetaxel-resistant CRPC tumor growth in soft tissue and bone greater than either
      agent alone. Antitumor activity was associated with PF-03084014-induced
      inhibition of Notch pathway signaling; decreased survival signals (cyclin E;
      MEK/ERK, PI3K/AKT, EGFR and NF-kappaB pathway; BCL-2, BCL-XL); increased
      apoptotic signals (BAK, BAX; cleaved caspase-3); reduced microvessel density;
      reduced epithelial-mesenchymal transition; and reduced cancer stem-like cells in
      the tumor. CONCLUSIONS: These results reveal that PF-03084014 enhances docetaxel
      mediated tumor response and provides a rationale to explore GSIs as adjunct
      therapy in conjunction with docetaxel for men with CRPC.

PMID- 26202951
TI  - Cellular Mechanisms Underlying Complete Hematological Response of Chronic Myeloid
      Leukemia to BRAF and MEK1/2 Inhibition in a Patient with Concomitant Metastatic
      Melanoma.
AB  - PURPOSE: Targeted MEK inhibition is an emerging therapy in a number of solid
      tumors. It holds particular promise in BRAF V600E mutation-positive malignant
      melanoma, where constitutive activation and cell growth through the MAP kinase
      (MAPK) pathway is well established. In vitro and preclinical research indicates
      that MAPK pathway activation is important in chronic myeloid leukemia (CML)
      leukemogenesis; however, the potential of MEK inhibition has not yet been
      investigated clinically in the setting of such hematologic malignancies.
      EXPERIMENTAL DESIGN: We report a case of complete hematologic response of CML to
      MEK inhibition in a patient with synchronous metastatic melanoma, who received
      treatment with combination BRAF and MEK1/2 inhibitors. We studied the effects of
      these agents on proliferation and outgrowth of myeloid precursors, and
      longitudinal shifts in peripheral blood phenotyping during the course of
      treatment. A model cell line system was used to examine the effects of dabrafenib
      and trametinib on MAPK and BCR-ABL1 signaling. RESULTS: After 35 weeks on
      treatment with BRAF and MEK inhibitors, complete hematologic response was
      observed without recourse to BCR-ABL1-targeted therapy. MEK inhibition was
      principally responsible for impaired proliferation of both mature and primitive
      myeloid precursors, as well as growth and hemoglobinization of erythroid
      precursors. Paradoxical activation of the MAPK pathway was seen in response to
      BRAF inhibitor therapy but this was easily overcome by clinically relevant doses
      of concurrent MEK inhibitor. CONCLUSIONS: These studies suggest that further
      evaluation of the optimal MAPK targeting approach is warranted to extend
      therapeutic options in CML.

PMID- 26202950
TI  - Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent
      Neuroblastoma.
AB  - PURPOSE: MYCN-dependent neuroblastomas have low cure rates with current
      multimodal treatment regimens and novel therapeutic drugs are therefore urgently
      needed. In previous preclinical studies, we have shown that targeted inhibition
      of cyclin-dependent kinase 2 (CDK2) resulted in specific killing of MYCN
      amplified neuroblastoma cells. This study describes the in vivo preclinical
      evaluation of the CDK inhibitor AT7519. EXPERIMENTAL DESIGN: Preclinical drug
      testing was performed using a panel of MYCN-amplified and MYCN single copy
      neuroblastoma cell lines and different MYCN-dependent mouse models of
      neuroblastoma. RESULTS: AT7519 killed MYCN-amplified neuroblastoma cell lines
      more potently than MYCN single copy cell lines with a median LC50 value of 1.7
      compared to 8.1 MUmol/L (P = 0.0053) and a significantly stronger induction of
      apoptosis. Preclinical studies in female NMRI homozygous (nu/nu) mice with
      neuroblastoma patient-derived MYCN-amplified AMC711T xenografts revealed dose
      dependent growth inhibition, which correlated with intratumoral AT7519 levels.
      CDK2 target inhibition by AT7519 was confirmed by significant reductions in
      levels of phosphorylated retinoblastoma (p-Rb) and nucleophosmin (p-NPM). AT7519
      treatment of Th-MYCN transgenic mice resulted in improved survival and clinically
      significant tumor regression (average tumor size reduction of 86% at day 7 after
      treatment initiation). The improved efficacy of AT7519 observed in Th-MYCN mice
      correlated with higher tumor exposure to the drug. CONCLUSIONS: This study
      strongly suggests that AT7519 is a promising drug for the treatment of high-risk
      neuroblastoma patients with MYCN amplification.

PMID- 26202953
TI  - Concise Review: Stem Cells in Pancreatic Cancer: From Concept to Translation.
AB  - Pancreatic cancer stem cells (CSCs) have been first described in 2007 and since
      then have emerged as an intriguing entity of cancer cells with distinct
      functional features including self-renewal and exclusive in vivo tumorigenicity.
      The heterogeneous pancreatic CSC pool has been implicated in tumor propagation as
      well as metastatic spread. Clinically, the most important feature of CSCs is
      their strong resistance to standard chemotherapy, which results in fast disease
      relapse, even with today's more advanced chemotherapeutic regimens. Therefore,
      novel therapeutic strategies to most efficiently target pancreatic CSCs are being
      developed and their careful clinical translation should provide new avenues to
      eradicate this deadly disease.

PMID- 26202954
TI  - Development of coupled ultrasound-assisted and reversed-phase dispersive liquid
      liquid microextraction before high-performance liquid chromatography for the
      sensitive determination of vitamin A and vitamin E in oil samples.
AB  - A new approach based on the ultrasound-assisted reversed-phase dispersive liquid
      liquid microextraction technique is developed for the extraction and
      determination of vitamin A and vitamin E from oil matrices before high
      performance liquid chromatography analysis. A methodology based on the full
      factorial design is carried out to choose the significant parameters. Then the
      significant factors affecting the extraction efficiency including pH, volume of
      extraction solvent, and volume of disperser solvent are optimized using a Box
      Behnken design. After analyzing the results obtained, the optimum conditions
      were: pH 4.5, 80-20 MUL of the ethanol/water solvent mixture as extraction
      solvent, 110 MUL of 1,4-dioxane as the disperser solvent, and a sonication time
      of 10 min. For validation of the developed method, the linear dynamic range,
      repeatability, limit of detection, and recoveries were obtained under the optimum
      conditions. The detection limits of the method were 1.6 and 2.3 ng/mL for vitamin
      A and vitamin E, respectively. The extraction recovery percentages for the
      studied drugs were above 91%, with acceptable relative standard deviation. The
      proposed methodology was successfully applied for the determination of the
      vitamins in different oil samples.

PMID- 26202952
TI  - Multiple Gastrointestinal Polyps in Patients Treated with BRAF Inhibitors.
AB  - PURPOSE: BRAF inhibitors (BRAFi) extend survival in BRAF-mutant melanoma but can
      promote the growth of Ras-mutant neoplasms. This study determined if
      gastrointestinal polyps found in BRAFi-treated patients harbored Ras mutations.
      EXPERIMENTAL DESIGN: Colonic and gastric polyps were identified and resected from
      BRAFi-treated melanoma patients. Next-generation sequencing (NGS) was performed
      on polyps. The ability of BRAFi to promote polyp formation was functionally
      characterized in Apc Min(+/-) mice. MAPK and beta-catenin pathway activity was
      assessed by immunohistochemistry in mouse and human polyps. RESULTS: Fourteen
      patients treated with BRAFi underwent endoscopy to assess for polyps. Seven out
      of 7 patients >40 years of age and treated for >2 years were found to have
      colonic tubular adenomas with 4 out of the 7 patients having 5 or more polyps.
      One patient presented with bleeding from hyperplastic gastric polyps that
      recurred 6 months after BRAFi rechallenge. NGS performed on polyps found no
      mutations in MAPK pathway genes, but found APC mutations in all tubular adenomas.
      A significant increase in the number of polyps was observed in BRAFi-treated
      compared with control-treated Apc Min(+/-) mice (20.8 +/- 9.2 vs 12.8 +/- 0.1; P
      = 0.016). No polyps were observed in BRAFi-treated wild-type mice. CONCLUSIONS:
      BRAFi may increase the risk of developing hyperplastic gastric polyps and colonic
      adenomatous polyps. Due to the risk of gastrointestinal bleeding and the
      possibility of malignant transformation, further studies are needed to determine
      whether or not endoscopic surveillance should be recommended for patients treated
      with BRAFi.

PMID- 26202955
TI  - The effect of spray drying on sucrose-glycine caramel powder preparation.
AB  - BACKGROUND: Caramel is used as food colorant in many parts of the world. However,
      there have been no studies investigating the effects of spray drying on sucrose
      and glycine solutions. In this study, model sucrose and glycine solutions at
      different pH levels (pH 4, 3, 2 and 1) were treated with different inlet air
      temperatures (160, 180, 200, 220 and 240  degrees C) for durations of 50 s in the
      spray drying process. RESULTS: With increasing inlet temperatures and decreasing
      pH, the morphology of the caramel agglomerates tended to be more scattered;
      however, the solubility of the caramel decreased. With increasing inlet
      temperature, the glycine and sucrose contents decreased but the fructose and
      glucose contents increased. CONCLUSION: The content of the intermediate products,
      browning intensity and amount of 5-hydroxymethyl-2-furaldehyde (HMF) increased
      with increasing inlet temperature and decreasing pH. Therefore, the amount of
      sucrose degradation and the change in pH can be used to evaluate caramel
      properties in the spray drying process. (c) 2015 Society of Chemical Industry.

PMID- 26202958
TI  - Intravenous bevacizumab for complications of hereditary hemorrhagic
      telangiectasia: a review of the literature.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a multisystem disease
      that is marked by mutations regulating vasculature formation. Epistaxis is the
      most commonly reported symptom, but gastrointestinal bleeding, anemia, hepatic
      issues, and pulmonary disease are also common. There is a growing body of
      evidence in the literature concerning using the monoclonal antibody against
      vascular endothelial growth factor (VEGF), bevacizumab, in patients with HHT.
      This treatment is gaining support for managing HHT because it directly inhibits
      the VEGF proteins that can be elevated as a result of the HHT mutations. We
      reviewed the current literature on the outcomes from intravenous bevacizumab
      treatment for HHT with a focus on epistaxis outcomes. METHODS: A systematic
      review of the literature was performed using Ovid MEDLINE, Scopus, and Cochrane
      databases. English citations, both national and international, were reviewed and
      filtered for relevance. RESULTS: Eighteen studies were included in this review.
      The majority of citations were case reports. All studies reported improvements.
      Specifically, 14 reported improvements in epistaxis, and 11 reported hemoglobin
      improvement following intravenous (IV) bevacizumab. Lack of uniformity in data
      presentation prevented a meta-analysis. CONCLUSION: This is the first systematic
      review analyzing the data involving HHT patients treated with bevacizumab. The
      results show that patients treated with bevacizumab have global improvements as
      well as specific improvements in hemoglobin levels. Although all of the studies
      reported improvements, there are several limitations, including inconsistencies
      in outcome reporting. A large, randomized, controlled study is needed to further
      investigate hemorrhage and epistaxis outcomes in HHT patients treated with
      intravenous bevacizumab.

PMID- 26202959
TI  - Crosstalk of parkin and Ret in dopaminergic neurons.

PMID- 26202960
TI  - IP3 3-kinase B prevents bone marrow failure.

PMID- 26202961
TI  - The yeast genome undergoes significant topological reorganization in quiescence.
AB  - We have examined the three-dimensional organization of the yeast genome during
      quiescence by a chromosome capture technique as a means of understanding how
      genome organization changes during development. For exponentially growing cells
      we observe high levels of inter-centromeric interaction but otherwise a
      predominance of intrachromosomal interactions over interchromosomal interactions,
      consistent with aggregation of centromeres at the spindle pole body and
      compartmentalization of individual chromosomes within the nucleoplasm. Three
      major changes occur in the organization of the quiescent cell genome. First,
      intrachromosomal associations increase at longer distances in quiescence as
      compared to growing cells. This suggests that chromosomes undergo condensation in
      quiescence, which we confirmed by microscopy by measurement of the
      intrachromosomal distances between two sites on one chromosome. This compaction
      in quiescence requires the condensin complex. Second, inter-centromeric
      interactions decrease, consistent with prior data indicating that centromeres
      disperse along an array of microtubules during quiescence. Third, inter-telomeric
      interactions significantly increase in quiescence, an observation also confirmed
      by direct measurement. Thus, survival during quiescence is associated with
      substantial topological reorganization of the genome. 

PMID- 26202962
TI  - Single cell measurement of telomerase expression and splicing using microfluidic
      emulsion cultures.
AB  - Telomerase is a reverse transcriptase that maintains telomeres on the ends of
      chromosomes, allowing rapidly dividing cells to proliferate while avoiding
      senescence and apoptosis. Understanding telomerase gene expression and splicing
      at the single cell level could yield insights into the roles of telomerase during
      normal cell growth as well as cancer development. Here we use droplet-based
      single cell culture followed by single cell or colony transcript abundance
      analysis to investigate the relationship between cell growth and transcript
      abundance of the telomerase genes encoding the RNA component (hTR) and protein
      component (hTERT) as well as hTERT splicing. Jurkat and K562 cells were examined
      under normal cell culture conditions and during exposure to curcumin, a natural
      compound with anti-carcinogenic and telomerase activity-reducing properties.
      Individual cells predominantly express single hTERT splice variants, with the
      alpha+/beta- variant exhibiting significant transcript abundance bimodality that
      is sustained through cell division. Sub-lethal curcumin exposure results in
      reduced bimodality of all hTERT splice variants and significant upregulation of
      alpha splicing, suggesting a possible role in cellular stress response. The
      single cell culture and transcript abundance analysis method presented here
      provides the tools necessary for multiparameter single cell analysis which will
      be critical for understanding phenotypes of heterogeneous cell populations,
      disease cell populations and their drug response. 

PMID- 26202963
TI  - Deciphering the principles that govern mutually exclusive expression of
      Plasmodium falciparum clag3 genes.
AB  - The product of the Plasmodium falciparum genes clag3.1 and clag3.2 plays a
      fundamental role in malaria parasite biology by determining solute transport into
      infected erythrocytes. Expression of the two clag3 genes is mutually exclusive,
      such that a single parasite expresses only one of the two genes at a time. Here
      we investigated the properties and mechanisms of clag3 mutual exclusion using
      transgenic parasite lines with extra copies of clag3 promoters located either in
      stable episomes or integrated in the parasite genome. We found that the
      additional clag3 promoters in these transgenic lines are silenced by default, but
      under strong selective pressure parasites with more than one clag3 promoter
      simultaneously active are observed, demonstrating that clag3 mutual exclusion is
      strongly favored but it is not strict. We show that silencing of clag3 genes is
      associated with the repressive histone mark H3K9me3 even in parasites with
      unusual clag3 expression patterns, and we provide direct evidence for
      heterochromatin spreading in P. falciparum. We also found that expression of a
      neighbor ncRNA correlates with clag3.1 expression. Altogether, our results reveal
      a scenario where fitness costs and non-deterministic molecular processes that
      favor mutual exclusion shape the expression patterns of this important gene
      family. 

PMID- 26202964
TI  - SUMOylation at K707 of DGCR8 controls direct function of primary microRNA.
AB  - DGCR8 (DiGeorge syndrome critical region gene 8) is essential for primary
      microRNA (pri-miRNA) processing in the cell nucleus. It specifically combines
      with Drosha, a nuclear RNase III enzyme, to form the Microprocessor complex (MC)
      that cleaves pri-miRNA to precursor miRNA (pre-miRNA), which is further processed
      to mature miRNA by Dicer, a cytoplasmic RNase III enzyme. Increasing evidences
      suggest that pri-/pre-miRNAs have direct functions in regulation of gene
      expression, however the underlying mechanism how it is fine-tuned remains
      unclear. Here we find that DGCR8 is modified by SUMO1 at the major site K(707),
      which can be promoted by its ERK-activated phosphorylation. SUMOylation of DGCR8
      enhances the protein stability by preventing the degradation via the ubiquitin
      proteasome pathway. More importantly, SUMOylation of DGCR8 does not alter its
      association with Drosha, the MC activity and miRNA biogenesis, but rather
      influences its affinity with pri-miRNAs. This altered affinity of DGCR8 with pri
      miRNAs seems to control the direct functions of pri-miRNAs in recognition and
      repression of the target mRNAs, which is evidently linked to the DGCR8 function
      in regulation of tumorigenesis and cell migration. Collectively, our data suggest
      a novel mechanism that SUMOylation of DGCR8 controls direct functions of pri
      miRNAs in gene silencing. 

PMID- 26202965
TI  - Conformation-sensitive nucleoside analogues as topology-specific fluorescence
      turn-on probes for DNA and RNA G-quadruplexes.
AB  - Development of probes that can discriminate G-quadruplex (GQ) structures and
      indentify efficient GQ binders on the basis of topology and nucleic acid type is
      highly desired to advance GQ-directed therapeutic strategies. In this context, we
      describe the development of minimally perturbing and environment-sensitive
      pyrimidine nucleoside analogues, based on a 5-(benzofuran-2-yl)uracil core, as
      topology-specific fluorescence turn-on probes for human telomeric DNA and RNA
      GQs. The pyrimidine residues of one of the loop regions (TTA) of telomeric DNA
      and RNA GQ oligonucleotide (ON) sequences were replaced with 5-benzofuran
      modified 2'-deoxyuridine and uridine analogues. Depending on the position of
      modification the fluorescent nucleoside analogues distinguish antiparallel, mixed
      parallel-antiparallel and parallel stranded DNA and RNA GQ topologies from
      corresponding duplexes with significant enhancement in fluorescence intensity and
      quantum yield. Further, these GQ sensors enabled the development of a simple
      fluorescence binding assay to quantify topology- and nucleic acid-specific
      binding of small molecule ligands to GQ structures. Together, our results
      demonstrate that these nucleoside analogues are useful GQ probes, which are
      anticipated to provide new opportunities to study and discover efficient G
      quadruplex binders of therapeutic potential. 

PMID- 26202966
TI  - Complex long-distance effects of mutations that confer linezolid resistance in
      the large ribosomal subunit.
AB  - The emergence of multidrug-resistant pathogens will make current antibiotics
      ineffective. For linezolid, a member of the novel oxazolidinone class of
      antibiotics, 10 nucleotide mutations in the ribosome have been described
      conferring resistance. Hypotheses for how these mutations affect antibiotics
      binding have been derived based on comparative crystallographic studies. However,
      a detailed description at the atomistic level of how remote mutations exert long
      distance effects has remained elusive. Here, we show that the G2032A-C2499A
      double mutation, located > 10 A away from the antibiotic, confers linezolid
      resistance by a complex set of effects that percolate to the binding site. By
      molecular dynamics simulations and free energy calculations, we identify U2504
      and C2452 as spearheads among binding site nucleotides that exert the most
      immediate effect on linezolid binding. Structural reorganizations within the
      ribosomal subunit due to the mutations are likely associated with mutually
      compensating changes in the effective energy. Furthermore, we suggest two main
      routes of information transfer from the mutation sites to U2504 and C2452.
      Between these, we observe cross-talk, which suggests that synergistic effects
      observed for the two mutations arise in an indirect manner. These results should
      be relevant for the development of oxazolidinone derivatives that are active
      against linezolid-resistant strains. 

PMID- 26202967
TI  - DeltaNp63 intronic miR-944 is implicated in the DeltaNp63-mediated induction of
      epidermal differentiation.
AB  - DeltaNp63 is required for both the proliferation and differentiation of
      keratinocytes, but its role in the differentiation of these cells is poorly
      understood. The corresponding gene, TP63, harbors the MIR944 sequence within its
      intron. However, the mechanism of biogenesis and the function of miR-944 are
      unknown. We found that miR-944 is highly expressed in keratinocytes, in a manner
      that is concordant with that of DeltaNp63 mRNA, but the regulation of miR-944
      expression under various conditions did not correspond with that of DeltaNp63.
      Bioinformatics analysis and functional studies demonstrated that MIR944 has its
      own promoter. We demonstrate here that MIR944 is a target of DeltaNp63. Promoter
      analysis revealed that the activity of the MIR944 promoter was markedly enhanced
      by the binding of DeltaNp63, which was maintained by the supportive action of AP
      2 during keratinocyte differentiation. Our results indicated that miR-944
      biogenesis is dependent on DeltaNp63 protein, even though it is generated from
      DeltaNp63 mRNA-independent transcripts. We also demonstrated that miR-944 induces
      keratin 1 and keratin 10 expression by inhibiting ERK signaling and upregulating
      p53 expression. Our findings suggested that miR-944, as an intronic miRNA and a
      direct target of DeltaNp63, contributes to the function of DeltaNp63 in the
      induction of epidermal differentiation.

PMID- 26202968
TI  - Splicing inhibition decreases phosphorylation level of Ser2 in Pol II CTD.
AB  - Phosphorylation of the C-terminal domain of the largest subunit of RNA polymerase
      II (Pol II), especially Ser2 and Ser5 residues, plays important roles in
      transcription and mRNA processing, including 5' end capping, splicing and 3' end
      processing. These phosphorylation events stimulate mRNA processing, however, it
      is not clear whether splicing activity affects the phosphorylation status of Pol
      II. In this study, we found that splicing inhibition by potent splicing
      inhibitors spliceostatin A (SSA) and pladienolide B or by antisense oligos
      against snRNAs decreased phospho-Ser2 level, but had little or no effects on
      phospho-Ser5 level. In contrast, transcription and translation inhibitors did not
      decrease phospho-Ser2 level, therefore inhibition of not all the gene expression
      processes cause the decrease of phospho-Ser2. SSA treatment caused early
      dissociation of Pol II and decrease in phospho-Ser2 level of chromatin-bound Pol
      II, suggesting that splicing inhibition causes downregulation of phospho-Ser2
      through at least these two mechanisms. 

PMID- 26202969
TI  - tRNA recognition by a bacterial tRNA Xm32 modification enzyme from the SPOUT
      methyltransferase superfamily.
AB  - TrmJ proteins from the SPOUT methyltransferase superfamily are tRNA Xm32
      modification enzymes that occur in bacteria and archaea. Unlike archaeal TrmJ,
      bacterial TrmJ require full-length tRNA molecules as substrates. It remains
      unknown how bacterial TrmJs recognize substrate tRNAs and specifically catalyze a
      2'-O modification at ribose 32. Herein, we demonstrate that all six Escherichia
      coli (Ec) tRNAs with 2'-O-methylated nucleosides at position 32 are substrates of
      EcTrmJ, and we show that the elbow region of tRNA, but not the amino acid
      acceptor stem, is needed for the methylation reaction. Our crystallographic study
      reveals that full-length EcTrmJ forms an unusual dimer in the asymmetric unit,
      with both the catalytic SPOUT domain and C-terminal extension forming separate
      dimeric associations. Based on these findings, we used electrophoretic mobility
      shift assay, isothermal titration calorimetry and enzymatic methods to identify
      amino acids within EcTrmJ that are involved in tRNA binding. We found that tRNA
      recognition by EcTrmJ involves the cooperative influences of conserved residues
      from both the SPOUT and extensional domains, and that this process is regulated
      by the flexible hinge region that connects these two domains.

PMID- 26202970
TI  - How data analysis affects power, reproducibility and biological insight of RNA
      seq studies in complex datasets.
AB  - The sequencing of the full transcriptome (RNA-seq) has become the preferred
      choice for the measurement of genome-wide gene expression. Despite its widespread
      use, challenges remain in RNA-seq data analysis. One often-overlooked aspect is
      normalization. Despite the fact that a variety of factors or 'batch effects' can
      contribute unwanted variation to the data, commonly used RNA-seq normalization
      methods only correct for sequencing depth. The study of gene expression is
      particularly problematic when it is influenced simultaneously by a variety of
      biological factors in addition to the one of interest. Using examples from
      experimental neuroscience, we show that batch effects can dominate the signal of
      interest; and that the choice of normalization method affects the power and
      reproducibility of the results. While commonly used global normalization methods
      are not able to adequately normalize the data, more recently developed RNA-seq
      normalization can. We focus on one particular method, RUVSeq and show that it is
      able to increase power and biological insight of the results. Finally, we provide
      a tutorial outlining the implementation of RUVSeq normalization that is
      applicable to a broad range of studies as well as meta-analysis of publicly
      available data. 

PMID- 26202971
TI  - G-quadruplex formation in double strand DNA probed by NMM and CV fluorescence.
AB  - G-quadruplexes (GQs) are alternative DNA secondary structures that can form
      throughout the human genome and control the replication and transcription of
      important regulatory genes. Here, we established an ensemble fluorescence assay
      by employing two GQ-interacting compounds, N-methyl mesoporphyrin IX (NMM) and
      Crystal Violet (CV). This enables quantitative measurement of the GQ folding
      propensity and conformation specificity in both single strand (ss) and double
      strand (ds) DNA. Our GQ mapping indicates that the likelihood of GQ formation is
      substantially diminished in dsDNA, likely due to the competition from the Watson
      Crick base pairing. Unlike GQ folding sequence in ssDNA which forms both parallel
      and antiparallel GQs, dsDNA displays only parallel folding. Additionally, we
      employed single molecule FRET to obtain a direct quantitation of stably formed-,
      weakly folded and unfolded GQ conformations. The findings of this study and the
      method developed here will enable identifying and classifying potential GQ
      forming sequences in human genome. 

PMID- 26202972
TI  - BayesPI-BAR: a new biophysical model for characterization of regulatory sequence
      variations.
AB  - Sequence variations in regulatory DNA regions are known to cause functionally
      important consequences for gene expression. DNA sequence variations may have an
      essential role in determining phenotypes and may be linked to disease; however,
      their identification through analysis of massive genome-wide sequencing data is a
      great challenge. In this work, a new computational pipeline, a Bayesian method
      for protein-DNA interaction with binding affinity ranking (BayesPI-BAR), is
      proposed for quantifying the effect of sequence variations on protein binding.
      BayesPI-BAR uses biophysical modeling of protein-DNA interactions to predict
      single nucleotide polymorphisms (SNPs) that cause significant changes in the
      binding affinity of a regulatory region for transcription factors (TFs). The
      method includes two new parameters (TF chemical potentials or protein
      concentrations and direct TF binding targets) that are neglected by previous
      methods. The new method is verified on 67 known human regulatory SNPs, of which
      47 (70%) have predicted true TFs ranked in the top 10. Importantly, the
      performance of BayesPI-BAR, which uses principal component analysis to integrate
      multiple predictions from various TF chemical potentials, is found to be better
      than that of existing programs, such as sTRAP and is-rSNP, when evaluated on the
      same SNPs. BayesPI-BAR is a publicly available tool and is able to carry out
      parallelized computation, which helps to investigate a large number of TFs or
      SNPs and to detect disease-associated regulatory sequence variations in the sea
      of genome-wide noncoding regions. 

PMID- 26202973
TI  - In vivo detection and replication studies of alpha-anomeric lesions of 2'
      deoxyribonucleosides.
AB  - DNA damage, arising from endogenous metabolism or exposure to environmental
      agents, may perturb the transmission of genetic information by blocking DNA
      replication and/or inducing mutations, which contribute to the development of
      cancer and likely other human diseases. Hydroxyl radical attack on the C1', C3'
      and C4' of 2-deoxyribose can give rise to epimeric 2-deoxyribose lesions, for
      which the in vivo occurrence and biological consequences remain largely
      unexplored. Through independent chemical syntheses of all three epimeric lesions
      of 2'-deoxyguanosine (dG) and liquid chromatography-tandem mass spectrometry
      analysis, we demonstrated unambiguously the presence of substantial levels of the
      alpha-anomer of dG (alpha-dG) in calf thymus DNA and in DNA isolated from mouse
      pancreatic tissues. We further assessed quantitatively the impact of all four
      alpha-dN lesions on DNA replication in Escherichia coli by employing a shuttle
      vector method. We found that, without SOS induction, all alpha-dN lesions except
      alpha-dA strongly blocked DNA replication and, while replication across alpha-dA
      was error-free, replicative bypass of alpha-dC and alpha-dG yielded mainly C->A
      and G->A mutations. In addition, SOS induction could lead to markedly elevated
      bypass efficiencies for the four alpha-dN lesions, abolished the G->A mutation
      for alpha-dG, pronouncedly reduced the C->A mutation for alpha-dC and triggered T
      >A mutation for alpha-dT. The preferential misincorporation of dTMP opposite the
      alpha-dNs could be attributed to the unique base-pairing properties of the
      nucleobases elicited by the inversion of the configuration of the N-glycosidic
      linkage. Our results also revealed that Pol V played a major role in bypassing
      alpha-dC, alpha-dG and alpha-dT in vivo. The abundance of alpha-dG in mammalian
      tissue and the impact of the alpha-dNs on DNA replication demonstrate for the
      first time the biological significance of this family of DNA lesions. 

PMID- 26202974
TI  - Allelome.PRO, a pipeline to define allele-specific genomic features from high
      throughput sequencing data.
AB  - Detecting allelic biases from high-throughput sequencing data requires an
      approach that maximises sensitivity while minimizing false positives. Here, we
      present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which
      uses high-throughput sequencing data from reciprocal crosses of two genetically
      distinct mouse strains to detect allele-specific expression and chromatin
      modifications. Allelome.PRO extends approaches used in previous studies that
      exclusively analyzed imprinted expression to give a complete picture of the
      'allelome' by automatically categorising the allelic expression of all genes in a
      given cell type into imprinted, strain-biased, biallelic or non-informative.
      Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts,
      together with a robust false discovery rate empirically calculated from variation
      in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts
      from F1 reciprocal crosses to determine a biologically relevant allelic ratio
      cutoff, and define for the first time an entire allelome. Furthermore, we show
      that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from
      ChIP-seq data validating the RNA-seq results. This approach can be easily
      extended to analyze histone marks of active enhancers, or transcription factor
      binding sites and therefore provides a powerful tool to identify candidate cis
      regulatory elements genome wide. 

PMID- 26202975
TI  - A design principle for a single-stranded RNA genome that replicates with less
      double-strand formation.
AB  - Single-stranded RNA (ssRNA) is the simplest form of genetic molecule and
      constitutes the genome in some viruses and presumably in primitive life-forms.
      However, an innate and unsolved problem regarding the ssRNA genome is formation
      of inactive double-stranded RNA (dsRNA) during replication. Here, we addressed
      this problem by focusing on the secondary structure. We systematically designed
      RNAs with various structures and observed dsRNA formation during replication
      using an RNA replicase (Qbeta replicase). From the results, we extracted a simple
      rule regarding ssRNA genome replication with less dsRNA formation (less GC number
      in loops) and then designed an artificial RNA that encodes a domain of the beta
      galactosidase gene based on this rule. We also obtained evidence that this rule
      governs the natural genomes of all bacterial and most fungal viruses presently
      known. This study revealed one of the structural design principles of an ssRNA
      genome that replicates continuously with less dsRNA formation. 

PMID- 26202977
TI  - Science hackathons for developing interdisciplinary research and collaborations.
AB  - Science hackathons can help academics, particularly those in the early stage of
      their careers, to build collaborations and write research proposals. 

PMID- 26202976
TI  - Genomic variations of the mevalonate pathway in porokeratosis.
AB  - Porokeratosis (PK) is a heterogeneous group of keratinization disorders. No
      causal genes except MVK have been identified, even though the disease was linked
      to several genomic loci. Here, we performed massively parallel sequencing and
      exonic CNV screening of 12 isoprenoid genes in 134 index PK patients (61 familial
      and 73 sporadic) and identified causal mutations in three novel genes (PMVK, MVD,
      and FDPS) in addition to MVK in the mevalonate pathway. Allelic expression
      imbalance (AEI) assays were performed in 13 lesional tissues. At least one
      mutation in one of the four genes in the mevalonate pathway was found in 60 (98%)
      familial and 53 (73%) sporadic patients, which suggests that isoprenoid
      biosynthesis via the mevalonate pathway may play a role in the pathogenesis of
      PK. Significantly reduced expression of the wild allele was common in lesional
      tissues due to gene conversion or some other unknown mechanism. A G-to-A RNA
      editing was observed in one lesional tissue without AEI. In addition, we observed
      correlations between the mutations in the four mevalonate pathway genes and
      clinical manifestations in the PK patients, which might support a new and
      simplified classification of PK under the guidance of genetic testing. 

PMID- 26202978
TI  - Externally validated predictive clinical model for untreated del(17p13.1) chronic
      lymphocytic leukemia patients.
AB  - Little is known about outcomes of patients with chronic lymphocytic leukemia
      (CLL) with del(17p13.1) karyotype at diagnosis. We reviewed 114 de novo
      del(17p13.1) CLL patients seen at our institution. Using proportional hazards
      models to identify pretreatment clinical variables significantly associated with
      treatment-free survival (TFS) and overall survival (OS), we developed a
      simplified risk score for de novo del(17p13.1) CLL patients to predict TFS and OS
      based on these variables. These scores, particularly the very highest, can be
      utilized to identify high-risk patients for expedient enrollment on clinical
      trials. Our data support careful observation for low-risk patients, potentially
      preventing unnecessary use of aggressive therapies.

PMID- 26202979
TI  - Atomic layer deposition modified track-etched conical nanochannels for protein
      sensing.
AB  - Nanopore-based devices have recently become popular tools to detect biomolecules
      at the single-molecule level. Unlike the long-chain nucleic acids, protein
      molecules are still quite challenging to detect, since the protein molecules are
      much smaller in size and usually travel too fast through the nanopore with poor
      signal-to-noise ratio of the induced transport signals. In this work, we
      demonstrate a new type of nanopore device based on atomic layer deposition (ALD)
      Al2O3 modified track-etched conical nanochannels for protein sensing. These
      devices show very promising properties of high protein (bovine serum albumin)
      capture rate with well time-resolved transport signals and excellent signal-to
      noise ratio for the transport events. Also, a special mechanism involving
      transient process of ion redistribution inside the nanochannel is proposed to
      explain the unusual biphasic waveshapes of the current change induced by the
      protein transport. 

PMID- 26202981
TI  - Identification of a New Exo-Endocytic Mechanism Triggered by Corticotropin
      Releasing Hormone in Mast Cells.
AB  - The key role of mast cells (MC), either in development of inflammatory
      pathologies or in response to environmental stress, has been widely reported in
      recent years. Previous studies have described the effects of corticotropin
      releasing hormone (CRH), which is released from inflamed tissues by cellular
      stress signals, on MC degranulation, a process possibly driven by selective
      secretion of mediators (piecemeal degranulation). In this study, we introduce a
      novel granular exo-endocytic pathway induced by CRH on peritoneal MC. We found
      that CRH triggers substantial exocytosis, which is even stronger than that
      induced by Ag stimulation and is characterized by large quantal size release
      events. Membrane fluorescence increases during stimulation in the presence of FM1
      43 dye, corroborating the strength of this exocytosis, given that discrete upward
      fluorescence steps are often observed and suggesting that secretory granules are
      preferentially released by compound exocytosis. Additionally, the presence of a
      depot of large tubular organelles in the cytoplasm suggests that the exocytotic
      process is tightly coupled to a fast compound endocytosis. This CRH-stimulated
      mechanism is mediated through activation of adenylate cyclase and an increase of
      cAMP and intracellular Ca(2+), as evidenced by the fact that the effect of CRH is
      mimicked by forskolin and 8-bromo-cAMP. Thus, these outcomes constitute new
      evidence for the critical role of MC in pathophysiological conditions within a
      cellular stress environment and an alternative membrane trafficking route
      mediated by CRH.

PMID- 26202980
TI  - Salmonella Typhimurium Co-Opts the Host Type I IFN System To Restrict Macrophage
      Innate Immune Transcriptional Responses Selectively.
AB  - Innate immune inflammatory responses are subject to complex layers of negative
      regulation at intestinal mucosal surfaces. Although the type I IFN system is
      critical for amplifying antiviral immunity, it has been shown to play a
      homeostatic role in some models of autoimmune inflammation. Type I IFN is
      triggered in the gut by select bacterial pathogens, but whether and how the type
      I IFN might regulate innate immunity in the intestinal environment have not been
      investigated in the context of Salmonella enterica serovar Typhimurium (ST). ST
      infection of human or murine macrophages reveals that IFN-beta selectively
      restricts the transcriptional responses mediated by both the TLRs and the NOD
      like receptors. Specifically, IFN-beta potently represses ST-dependent innate
      induction of IL-1 family cytokines and neutrophil chemokines. This IFN-beta
      mediated transcriptional repression was independent of the effects of IFN-beta on
      ST-induced macrophage cell death, but significantly dependent on IL-10
      regulation. We further evaluated ST pathogenesis in vivo following oral
      inoculation of mice lacking IFN-beta. We show that IFN-beta(-/-) mice exhibit
      greater resistance to oral ST infection and a slower spread of ST to distal
      sterile sites. This work provides mechanistic insight into the relationship
      between ST and type I IFN, and demonstrates an additional mechanism by which IFN
      beta may promote spread of enteric pathogens.

PMID- 26202982
TI  - Contribution of MINCLE-SYK Signaling to Activation of Primary Human APCs by
      Mycobacterial Cord Factor and the Novel Adjuvant TDB.
AB  - Trehalose-6,6-dimycolate (TDM), the mycobacterial cord factor, is an abundant
      cell wall glycolipid and major virulence factor of Mycobacterium tuberculosis.
      Its synthetic analog trehalose-6,6-dibehenate (TDB) is a new adjuvant currently
      in phase I clinical trials. In rodents, the C-type lectin receptors Mincle and
      Mcl bind TDB/TDM and activate macrophages and dendritic cells (DC) through the
      Syk-Card9 pathway. However, it is unknown whether these glycolipids activate
      human innate immune cells through the same mechanism. We performed in vitro
      analysis of TDB/TDM-stimulated primary human monocytes, macrophages, and DC;
      determined C-type lectin receptor expression; and tested the contribution of SYK,
      MINCLE, and MCL by small interfering RNA knockdown and genetic complementation.
      We observed a robust chemokine and cytokine release in response to TDB or TDM.
      MCSF-driven macrophages secreted higher levels of IL-8, IL-6, CCL3, CCL4, and
      CCL2 after stimulation with TDM, whereas DC responded more strongly to TDB and GM
      CSF-driven macrophages were equally responsive to TDB and TDM. SYK kinase and the
      adaptor protein CARD9 were essential for glycolipid-induced IL-8 production. mRNA
      expression of MINCLE and MCL was high in monocytes and macrophages, with MINCLE
      and MCL proteins localized intracellularly under resting conditions. Small
      interfering RNA-mediated MINCLE or MCL knockdown caused on average reduced TDB-
      or TDM-induced IL-8 production. Conversely, retroviral expression in murine
      Mincle-deficient DC revealed that human MINCLE, but not MCL, was sufficient to
      confer responsiveness to TDB/TDM. Our study demonstrates that SYK-CARD9 signaling
      plays a key role in TDB/TDM-induced activation of innate immune cells in man as
      in mouse, likely by engagement of MINCLE.

PMID- 26202983
TI  - MicroRNA-15b Modulates Japanese Encephalitis Virus-Mediated Inflammation via
      Targeting RNF125.
AB  - Japanese encephalitis virus (JEV) can target CNS and cause neuroinflammation that
      is characterized by profound neuronal damage and concomitant
      microgliosis/astrogliosis. Although microRNAs (miRNAs) have emerged as a major
      regulatory network with profound effects on inflammatory response, it is less
      clear how they regulate JEV-induced inflammation. In this study, we found that
      miR-15b is involved in modulating the JEV-induced inflammatory response. The data
      demonstrate that miR-15b is upregulated during JEV infection of glial cells and
      mouse brains. In vitro overexpression of miR-15b enhances the JEV-induced
      inflammatory response, whereas inhibition of miR-15b decreases it.
      Mechanistically, ring finger protein 125 (RNF125), a negative regulator of RIG-I
      signaling, is identified as a direct target of miR-15b in the context of JEV
      infection. Furthermore, inhibition of RNF125 by miR-15b results in an elevation
      in RIG-I levels, which, in turn, leads to a higher production of proinflammatory
      cytokines and type I IFN. In vivo knockdown of virus-induced miR-15b by antagomir
      15b restores the expression of RNF125, reduces the production of inflammatory
      cytokines, attenuates glial activation and neuronal damage, decreases viral
      burden in the brain, and improves survival in the mouse model. Taken together,
      our results indicate that miR-15b modulates the inflammatory response during JEV
      infection by negative regulation of RNF125 expression. Therefore, miR-15b
      targeting may constitute an interesting and promising approach to control viral
      induced neuroinflammation.

PMID- 26202984
TI  - Localized Store-Operated Calcium Influx Represses CD95-Dependent Apoptotic
      Effects of Rituximab in Non-Hodgkin B Lymphomas.
AB  - The anti-CD20 mAb, rituximab, is routinely used to treat B cell malignancies.
      However, a majority of patients relapse. An improvement in the complete response
      was obtained by combining rituximab with chemotherapy, at the cost of increased
      toxicity. We reported that rituximab induced the colocalization of both the Orai1
      Ca(2+) release-activated Ca(2+) channel (CRAC) and the endoplasmic reticulum
      Ca(2+) sensor stromal interaction molecule 1 with CD20 and CD95 into a cluster,
      eliciting a polarized store-operated Ca(2+) entry (SOCE). We observed that
      blocking this Ca(2+) entry with downregulation of Orai1, pharmacological
      inhibitors, or reducing calcemia with hypocalcemic drugs sensitized human B
      lymphoma cell lines and primary human lymphoma cells to rituximab-induced
      apoptosis in vitro, and improved the antitumoral effect of rituximab in
      xenografted mice. This revealed that Ca(2+) entry exerted a negative feedback
      loop on rituximab-induced apoptosis, suggesting that associating CRAC channel
      inhibitors or hypocalcemic agents with rituximab may improve the treatment of
      patients with B cell malignancies. The calcium-dependent proteins involved in
      this process appear to vary according to the B lymphoma cell type, suggesting
      that CRAC-channel targeting is likely to be more efficient than calcium-dependent
      protein targeting.

PMID- 26202985
TI  - Radiosensitive Hematopoietic Cells Determine the Extent of Skin Inflammation in
      Experimental Epidermolysis Bullosa Acquisita.
AB  - Animal models have enhanced our understanding of the pathogenesis of autoimmune
      diseases. For these models, genetically identical, inbred mice have commonly been
      used. Different inbred mouse strains, however, show a high variability in disease
      manifestation. Identifying the factors that influence this disease variability
      could provide unrecognized insights into pathogenesis. We established a novel Ab
      transfer-induced model of epidermolysis bullosa acquisita (EBA), an autoimmune
      disease characterized by (muco)-cutaneous blistering caused by anti-type VII
      collagen (COL7) autoantibodies. Blistering after anti-COL7 IgG (directed against
      the von Willebrand factor A-like domain 2) transfer showed clear variability
      among inbred mouse strains, that is, severe cutaneous blistering and inflammation
      in C57BL/6J and absence of skin lesions in MRL/MpJ mice. The transfer of anti
      COL7 IgG into irradiated, EBA-resistant MRL/MpJ mice, rescued by transplantation
      with bone marrow from EBA-susceptible B6.AK-H2k mice, induced blistering. To the
      contrary, irradiated EBA-susceptible B6.AK-H2k mice that were rescued using
      MRL/MpJ bone marrow were devoid of blistering. In vitro, immune complex
      activation of neutrophils from C57BL/6J or MRL/MpJ mice showed an impaired
      reactive oxygen species release from the latter, whereas no differences were
      observed after PMA activation. This finding was paralleled by divergent
      expression profiles of immune complex-activated neutrophils from either C57BL/6J
      or MRL/MpJ mice. Collectively, we demonstrate that radiosensitive cells determine
      the varying extent of skin inflammation and blistering in the end-stage effector
      phase of EBA.

PMID- 26202986
TI  - gamma-Tilmanocept, a New Radiopharmaceutical Tracer for Cancer Sentinel Lymph
      Nodes, Binds to the Mannose Receptor (CD206).
AB  - gamma-Tilmanocept ((99m)Tc-labeled-tilmanocept or [(99m)Tc]-tilmanocept) is the
      first mannose-containing, receptor-directed, radiolabeled tracer for the highly
      sensitive imaging of sentinel lymph nodes in solid tumor staging. To elucidate
      the mannose-binding receptor that retains tilmanocept in this microenvironment,
      human macrophages were used that have high expression of the C-type lectin
      mannose receptor (MR; CD206). Cy3-labeled tilmanocept exhibited high specificity
      binding to macrophages that was nearly abolished in competitive inhibition
      experiments. Furthermore, Cy3-tilmanocept binding was markedly reduced on
      macrophages deficient in the MR by small interfering RNA treatment and was
      increased on MR-transfected HEK 293 cells. Finally, confocal microscopy revealed
      colocalization of Cy3-tilmanocept with the macrophage membrane MR and binding of
      labeled tilmanocept to MR(+) cells (macrophages and/or dendritic cells) in human
      sentinel lymph node tissues. Together these data provide strong evidence that
      CD206 is a major binding receptor for gamma-tilmanocept. Identification of CD206
      as the gamma-tilmanocept-binding receptor enables opportunities for designing
      receptor-targeted advanced imaging agents and therapeutics for cancer and other
      diseases.

PMID- 26202987
TI  - Phosphocholine-Modified Macromolecules and Canonical Nicotinic Agonists Inhibit
      ATP-Induced IL-1beta Release.
AB  - IL-1beta is a potent proinflammatory cytokine of the innate immune system that is
      involved in host defense against infection. However, increased production of IL
      1beta plays a pathogenic role in various inflammatory diseases, such as
      rheumatoid arthritis, gout, sepsis, stroke, and transplant rejection. To prevent
      detrimental collateral damage, IL-1beta release is tightly controlled and
      typically requires two consecutive danger signals. LPS from Gram-negative
      bacteria is a prototypical first signal inducing pro-IL-1beta synthesis, whereas
      extracellular ATP is a typical second signal sensed by the ATP receptor P2X7 that
      triggers activation of the NLRP3-containing inflammasome, proteolytic cleavage of
      pro-IL-1beta by caspase-1, and release of mature IL-1beta. Mechanisms controlling
      IL-1beta release, even in the presence of both danger signals, are needed to
      protect from collateral damage and are of therapeutic interest. In this article,
      we show that acetylcholine, choline, phosphocholine, phosphocholine-modified LPS
      from Haemophilus influenzae, and phosphocholine-modified protein efficiently
      inhibit ATP-mediated IL-1beta release in human and rat monocytes via nicotinic
      acetylcholine receptors containing subunits alpha7, alpha9, and/or alpha10. Of
      note, we identify receptors for phosphocholine-modified macromolecules that are
      synthesized by microbes and eukaryotic parasites and are well-known modulators of
      the immune system. Our data suggest that an endogenous anti-inflammatory
      cholinergic control mechanism effectively controls ATP-mediated release of IL
      1beta and that the same mechanism is used by symbionts and misused by parasites
      to evade innate immune responses of the host.

PMID- 26202989
TI  - Effect of Sema4D on microglial function in middle cerebral artery occlusion mice.
AB  - Cerebral ischemia evokes neuroinflammatory response. Inflammatory stimulation
      induces microglial activation, such as changes of their morphology from ramified
      to ameboid, expression of iNOS and cytokines, and the elevation of proliferative
      activity. Activated microglia play important roles in pathogenesis of cerebral
      ischemia. A previous study indicated that Sema4D promoted iNOS expression in
      cultured microglia; however, roles of Sema4D on microglial activation in ischemic
      injury remains unclear. We investigated the effect of Sema4D-deficiency on
      microglial activation by using permanent middle cerebral artery occlusion (MCAO)
      in mice. In this study, ischemia-induced activated microglia were classified into
      activated-ramified microglia and ameboid microglia based on their morphology. We
      demonstrated that the rate of iNOS expression in activated-ramified microglia was
      lower than that in ameboid microglia, while the most proliferating microglia were
      activated-ramified microglia but not ameboid microglia after cerebral ischemia.
      Sema4D-deficiency decreased the number of ameboid microglia and iNOS-expressing
      activated-ramified microglia in the peri-ischemic cortex. These changes by Sema4D
      deficiency contributed to the reduction of NO production that was estimated by
      nitrite concentration in ischemic cortex. On the other hand, Sema4D-deficiency
      promoted proliferation of microglia in the peri-ischemic cortex. Importantly,
      ischemia-induced apoptosis and postischemic behavioral abnormality were moderated
      in Sema4D(-/-) mice. These findings suggest that Sema4D promotes cytotoxic
      activation of microglia and inhibits functional recovery after cerebral ischemia.

PMID- 26202988
TI  - Parasite Antigen-Specific Regulation of Th1, Th2, and Th17 Responses in
      Strongyloides stercoralis Infection.
AB  - Chronic helminth infections are known to be associated with modulation of Ag
      specific CD4(+) T responses. However, the role of CD4(+) T cell responses in
      human infection with Strongyloides stercoralis is not well defined. To examine
      the role of CD4(+) T cells expressing Th1, Th2, and Th17 cytokines in
      strongyloidiasis, we compared the frequency (Fo) of these subsets in infected
      (INF) individuals with Fo in S. stercoralis-uninfected (UN) individuals. INF
      individuals exhibited a significant decrease in the spontaneous and Ag-specific
      Fo of both monofunctional and dual-functional Th1 cells compared with UN.
      Similarly, INF individuals also exhibited significantly decreased Fo of
      monofunctional and dual-functional Th17 cells upon Ag stimulation compared with
      UN. In contrast, both the spontaneous and the Ag-induced Fo of monofunctional and
      dual-functional Th2 cells was significantly increased in INF compared with UN
      individuals. This differential T cell response was predominantly Ag specific
      because it was abrogated upon control Ag or mitogen stimulation. The regulation
      of Th1, Th2, and Th17 cells was predominantly dependent on IL-10, whereas the
      regulation of Th2, but not Th1 or Th17, cells was also dependent on TGF-beta. In
      addition, treatment of S. stercoralis infection significantly increased the Ag
      specific Fo of Th1 and Th17 cells and decreased the Fo of Th2 cells in INF
      individuals. Thus, S. stercoralis infection is characterized by a parasite Ag
      dependent regulation of monofunctional and dual-functional Th1, Th2, and Th17
      cells, a regulation also reversible by antihelminthic treatment.

PMID- 26202990
TI  - Flow cytometry analysis of CD4+IFN-gamma+ T-cells for the diagnosis of
      mycobacterium tuberculosis infection.
AB  - BACKGROUND: CD4+ cells expressing Interferon-gamma (IFN-gamma), following
      stimulation with specific mycobacterial antigens, identified with flow cytometry
      (FCM-CD4+IFN-gamma+), is a new method for the diagnosis of Mycobacterium
      tuberculosis (MTB) infection. The aim of this study is to investigate the
      performance of FCM-CD4+IFN-gamma+ in comparison with tuberculin skin test (TST)
      and Quantiferon TB Gold In-Tube (QFT-G-IT) in the diagnosis of latent MTB
      infection (LTBI), in close contacts and in patients with rheumatic diseases under
      treatment with anti-TNFa and other biologic agents. METHODS: TST, QFT-G-IT, and
      FCM-CD4+IFN-gamma+ were performed in 56 immunocompetent close contacts and in 65
      medically immunosuppressed patients under biologic treatment. RESULTS: In close
      contacts, 63% were FCM-CD4+IFN-gamma+ ESAT-6(+), 70% FCM-CD4+IFN-gamma+ PPD(+),
      41% QFT-G-IT(+) and 57% TST(+). FCM-CD4+IFN-gamma+ ESAT-6 was the only test that
      was strongly correlated to the exposure time to infection. In the
      immunosuppressed group, 49% were FCM-CD4+IFN-gamma+ ESAT-6(+), 62% FCM-CD4+IFN
      gamma+ PPD(+), 4.6% QFT-G-IT(+), and 18% TST(+). CONCLUSION: FCM-CD4+IFN-gamma+
      assays are more sensitive than QFT-G-IT and TST for the diagnosis of LTBI in
      close contacts and in immunosuppressed patients under anti-TNF-a treatment. FCM
      CD4+IFN-gamma+ is not affected by the chronic use of biologic agents. (c) 2015
      International Clinical Cytometry Society.

PMID- 26202991
TI  - Online Recruitment Methods for Web-Based and Mobile Health Studies: A Review of
      the Literature.
AB  - BACKGROUND: Internet and mobile health (mHealth) apps hold promise for expanding
      the reach of evidence-based health interventions. Research in this area is
      rapidly expanding. However, these studies may experience problems with
      recruitment and retention. Web-based and mHealth studies are in need of a wide
      reaching and low-cost method of recruitment that will also effectively retain
      participants for the duration of the study. Online recruitment may be a low-cost
      and wide-reaching tool in comparison to traditional recruitment methods, although
      empirical evidence is limited. OBJECTIVE: This study aims to review the
      literature on online recruitment for, and retention in, mHealth studies. METHODS:
      We conducted a review of the literature of studies examining online recruitment
      methods as a viable means of obtaining mHealth research participants. The data
      sources used were PubMed, CINAHL, EbscoHost, PyscINFO, and MEDLINE. Studies
      reporting at least one method of online recruitment were included. A narrative
      approach enabled the authors to discuss the variability in recruitment results,
      as well as in recruitment duration and study design. RESULTS: From 550 initial
      publications, 12 studies were included in this review. The studies reported
      multiple uses and outcomes for online recruitment methods. Web-based recruitment
      was the only type of recruitment used in 67% (8/12) of the studies. Online
      recruitment was used for studies with a variety of health domains: smoking
      cessation (58%; 7/12) and mental health (17%; 2/12) being the most common.
      Recruitment duration lasted under a year in 67% (8/12) of the studies, with an
      average of 5 months spent on recruiting. In those studies that spent over a year
      (33%; 4/12), an average of 17 months was spent on recruiting. A little less than
      half (42%; 5/12) of the studies found Facebook ads or newsfeed posts to be an
      effective method of recruitment, a quarter (25%; 3/12) of the studies found
      Google ads to be the most effective way to reach participants, and one study
      showed better outcomes with traditional (eg in-person) methods of recruitment.
      Only one study recorded retention rates in their results, and half (50%; 6/12) of
      the studies recorded survey completion rates. CONCLUSIONS: Although online
      methods of recruitment may be promising in experimental research, more empirical
      evidence is needed to make specific recommendations. Several barriers to using
      online recruitment were identified, including participant retention. These unique
      challenges of virtual interventions can affect the generalizability and validity
      of findings from Web-based and mHealth studies. There is a need for additional
      research to evaluate the effectiveness of online recruitment methods and
      participant retention in experimental mHealth studies.

PMID- 26202992
TI  - Suigetsumonas clinomigrationis gen. et sp. nov., a Novel Facultative Anaerobic
      Nanoflagellate Isolated from the Meromictic Lake Suigetsu, Japan.
AB  - A novel facultative anaerobic bacterivorous nanoflagellate was isolated from the
      water just below the permanent oxic-anoxic interface of the meromictic Lake
      Suigetsu, Japan. We characterized the isolate using light and transmission
      electron microscopy and molecular phylogenetic analyses inferred from 18S rDNA
      sequences. The phylogenetic analyses showed that the isolate belonged to class
      Placididea (stramenopiles). The isolate showed key ultrastructural features of
      the Placididea, such as flagellar hairs with two unequal terminal filaments,
      microtubular root 2 changing in shape from an arced to an acute-angled shape, and
      a lack of an x-fiber in root 2. However, the isolate had a single helix in the
      flagellar transition region, which is a double helix in the two known placidid
      nanoflagellates Placidia cafeteriopsis and Wobblia lunata. Moreover, the isolate
      had different intracellular features compared with these two genera, such as the
      arrangement of basal bodies, the components of the flagellar apparatus, the
      number of mitochondria, and the absence (or presence) of paranuclear bodies. The
      18S rDNA sequence was also phylogenetically distant from the clades of the known
      Placididae W. lunata and P. cafeteriopsis. Consequently, the newly isolated
      nanoflagellate was described as Suigetsumonas clinomigrationis gen. et sp. nov. 

PMID- 26202993
TI  - Diversity of Heterotrophic Protists from Extremely Hypersaline Habitats.
AB  - Heterotrophic protists (protozoa) are a diverse but understudied component of the
      biota of extremely hypersaline environments, with few data on molecular diversity
      within halophile 'species', and almost nothing known of their biogeographic
      distribution. We have garnered SSU rRNA gene sequences for several clades of
      halophilic protozoa from enrichments from waters of >12.5% salinity from
      Australia, North America, and Europe (6 geographic sites, 25 distinct samples).
      The small stramenopile Halocafeteria was found at all sites, but phylogenies did
      not show clear geographic clustering. The ciliate Trimyema was recorded from 6
      non-European samples. Phylogenies confirmed a monophyletic halophilic Trimyema
      group that included possible south-eastern Australian, Western Australian and
      North American clusters. Several halophilic Heterolobosea were detected,
      demonstrating that Pleurostomum contains at least three relatively distinct
      clades, and increasing known continental ranges for Tulamoeba peronaphora and
      Euplaesiobystra hypersalinica. The unclassified flagellate Palustrimonas, found
      in one Australian sample, proves to be a novel deep-branching alveolate. These
      results are consistent with a global distribution of halophilic protozoa groups
      (~ morphospecies), but the Trimyema case suggests that is worth testing whether
      larger forms exhibit biogeographic phylogenetic substructure. The molecular
      detection/characterization of halophilic protozoa is still far from complete at
      the clade level, let alone the 'species level'.

PMID- 26202994
TI  - Efficacy and Safety of 2% and 4% Articaine for Lower Third Molar Surgery.
AB  - This double-blind crossover randomized clinical trial compared the efficacy of 2
      concentrations of articaine, 2% (A2) and 4% (A4), with 1:200,000 epinephrine, for
      lower third molar removal. During 2 separate appointments with either A2 or A4,
      both similarly positioned lower third molars in 46 volunteers were extracted. The
      following were evaluated: onset and duration of anesthetic action on soft
      tissues, intraoperative bleeding, hemodynamic parameters, postoperative
      analgesia, and mouth opening and wound healing during the 7th postoperative day,
      along with the incidence, type, and severity of adverse reactions. Nearly
      identical volumes of both anesthetic solutions were used for each appointment:
      3.4 +/- 0.9 mL ~ 68 mg of articaine (A2) and 3.3 +/- 0.8 mL ~ 132 mg of articaine
      (A4). Statistical analysis indicated no differences in onset or duration of
      anesthetic action on soft tissues or duration of postoperative analgesia evoked
      by A2 and A4 anesthetic solutions (P > 0.05). The surgeon's rating of
      intraoperative bleeding was considered minimal throughout all surgery with both
      anesthetic solutions. While transient changes in blood pressure, heart rate, and
      oxygen saturation were observed, these factors were clinically insignificant and
      were uninfluenced by articaine concentration (P > 0.05). No systemic or local
      adverse reactions were observed in the preoperative and postoperative periods due
      to A2 or A4, but 1 case of bilateral paresthesia was observed. There were no
      significant differences between preoperative and postoperative (7th day) values
      of mouth opening and wound healing whether volunteers received A2 or A4 (P >
      0.05). In conclusion, both A2 and A4, administered in equal volumes, were
      effective and safe during lower third molar surgery, and no significant
      differences were found between their efficacy and safety (ClinicalTrials.gov
      NCT02457325).

PMID- 26202995
TI  - Effect of Probiotic Bacteria on Oral Candida in Frail Elderly.
AB  - The aim of this study was to investigate the effect of a daily intake of
      probiotic lactobacilli on the prevalence and counts of oral Candida in frail
      elderly patients living in nursing homes. The study had a double-blind randomized
      placebo-controlled design with 2 parallel arms. The study group consisted of 215
      older adults (range, 60 to 102 y) who were enrolled after informed consent. After
      baseline examination and randomization, the subjects were given 1 lozenge
      containing 2 strains of the probiotic bacterium Lactobacillus reuteri (DSM 17938
      and ATCC PTA 5289) or placebo twice daily (morning and evening). The intervention
      period was 12 wk, and saliva and plaque samples were collected at baseline and
      follow-up. The primary end point was prevalence of high Candida counts assessed
      from chairside tests. Secondary end points were levels of dental plaque and
      gingival inflammation. The groups were balanced at baseline. The attrition rate
      to follow-up was 19%. There was a statistically significant reduction in the
      prevalence of high Candida counts in the probiotic group but not in the placebo
      group, and the difference was statistically significant in both saliva and plaque
      (P < 0.05). No significant differences between the groups were noted concerning
      the levels of supragingival plaque or bleeding on probing. Thus, daily use of
      probiotic lozenges may reduce the prevalence of high oral Candida counts in frail
      elderly nursing homes residents (ClinicalTrials.gov NCT02391532). 

PMID- 26202996
TI  - Computerized Tool to Manage Dental Anxiety: A Randomized Clinical Trial.
AB  - Anxiety regarding dental and physical health is a common and potentially
      distressing problem, for both patients and health care providers. Anxiety has
      been identified as a barrier to regular dental visits and as an important target
      for enhancement of oral health-related quality of life. The study aimed to
      develop and evaluate a computerized cognitive-behavioral therapy dental anxiety
      intervention that could be easily implemented in dental health care settings. A
      cognitive-behavioral protocol based on psychoeducation, exposure to feared dental
      procedures, and cognitive restructuring was developed. A randomized controlled
      trial was conducted (N = 151) to test its efficacy. Consenting adult dental
      patients who met inclusion criteria (e.g., high dental anxiety) were randomized
      to 1 of 2 groups: immediate treatment (n = 74) or a wait-list control (n = 77).
      Analyses of covariance based on intention-to-treat analyses were used to compare
      the 2 groups on dental anxiety, fear, avoidance, and overall severity of dental
      phobia. Baseline scores on these outcomes were entered into the analyses as
      covariates. Groups were equivalent at baseline but differed at 1-mo follow-up.
      Both groups showed improvement in outcomes, but analyses of covariance
      demonstrated significant differences in dental anxiety, fear, avoidance, and
      overall severity of dental phobia in favor of immediate treatment at the follow
      up assessment. Of the patients who met diagnostic criteria for phobia at
      baseline, fewer patients in the immediate treatment group continued to meet
      criteria for dental phobia at follow-up as compared with the wait-list group. A
      new computer-based tool seems to be efficacious in reducing dental anxiety and
      fear/avoidance of dental procedures. Examination of its effectiveness when
      administered in dental offices under less controlled conditions is warranted
      (ClinicalTrials.gov NCT02081365). 

PMID- 26202997
TI  - Estimating the prevalence of any impairing childhood mental disorder in the
      national health interview survey.
AB  - This study investigates whether the six-item Strengths and Difficulties
      Questionnaire SDQ (five symptoms and one impact item) included in the National
      Health Interview Survey (NHIS) can be used to construct models that accurately
      estimate the prevalence of any impairing mental disorder among children 4-17
      years old as measured by a shortened Child/Adolescent or Preschool Age
      Psychiatric Assessment (CAPA or PAPA). A subsample of 217 NHIS respondents
      completed a follow-up CAPA or PAPA interview. Logistic regression models were
      developed to model presence of any child mental disorder with impairment (MDI) or
      with severe impairment (MDSI). Models containing only the SDQ impact item
      exhibited highly biased prevalence estimates. The best-performing model included
      information from both the five symptom SDQ items and the impact item, where
      absolute bias was reduced and sensitivity and concordance were increased. This
      study illustrates the importance of using all available information from the six
      item SDQ to accurately estimate the prevalence of any impairing childhood mental
      disorder from the NHIS. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26202998
TI  - The domestication of Amazonia before European conquest.
AB  - During the twentieth century, Amazonia was widely regarded as relatively pristine
      nature, little impacted by human history. This view remains popular despite
      mounting evidence of substantial human influence over millennial scales across
      the region. Here, we review the evidence of an anthropogenic Amazonia in response
      to claims of sparse populations across broad portions of the region. Amazonia was
      a major centre of crop domestication, with at least 83 native species containing
      populations domesticated to some degree. Plant domestication occurs in
      domesticated landscapes, including highly modified Amazonian dark earths (ADEs)
      associated with large settled populations and that may cover greater than 0.1% of
      the region. Populations and food production expanded rapidly within land
      management systems in the mid-Holocene, and complex societies expanded in
      resource-rich areas creating domesticated landscapes with profound impacts on
      local and regional ecology. ADE food production projections support estimates of
      at least eight million people in 1492. By this time, highly diverse regional
      systems had developed across Amazonia where subsistence resources were created
      with plant and landscape domestication, including earthworks. This review argues
      that the Amazonian anthrome was no less socio-culturally diverse or populous than
      other tropical forested areas of the world prior to European conquest. 

PMID- 26202999
TI  - Bayesian analysis of a morphological supermatrix sheds light on controversial
      fossil hominin relationships.
AB  - The phylogenetic relationships of several hominin species remain controversial.
      Two methodological issues contribute to the uncertainty-use of partial,
      inconsistent datasets and reliance on phylogenetic methods that are ill-suited to
      testing competing hypotheses. Here, we report a study designed to overcome these
      issues. We first compiled a supermatrix of craniodental characters for all widely
      accepted hominin species. We then took advantage of recently developed Bayesian
      methods for building trees of serially sampled tips to test among hypotheses that
      have been put forward in three of the most important current debates in hominin
      phylogenetics--the relationship between Australopithecus sediba and Homo, the
      taxonomic status of the Dmanisi hominins, and the place of the so-called hobbit
      fossils from Flores, Indonesia, in the hominin tree. Based on our results,
      several published hypotheses can be statistically rejected. For example, the data
      do not support the claim that Dmanisi hominins and all other early Homo specimens
      represent a single species, nor that the hobbit fossils are the remains of small
      bodied modern humans, one of whom had Down syndrome. More broadly, our study
      provides a new baseline dataset for future work on hominin phylogeny and
      illustrates the promise of Bayesian approaches for understanding hominin
      phylogenetic relationships.

PMID- 26203000
TI  - Adaptive developmental plasticity: what is it, how can we recognize it and when
      can it evolve?
AB  - Developmental plasticity describes situations where a specific input during an
      individual's development produces a lasting alteration in phenotype. Some
      instances of developmental plasticity may be adaptive, meaning that the tendency
      to produce the phenotype conditional on having experienced the developmental
      input has been under positive selection. We discuss the necessary assumptions and
      predictions of hypotheses concerning adaptive developmental plasticity (ADP) and
      develop guidelines for how to test empirically whether a particular example is
      adaptive. Central to our analysis is the distinction between two kinds of ADP:
      informational, where the developmental input provides information about the
      future environment, and somatic state-based, where the developmental input
      enduringly alters some aspect of the individual's somatic state. Both types are
      likely to exist in nature, but evolve under different conditions. In all cases of
      ADP, the expected fitness of individuals who experience the input and develop the
      phenotype should be higher than that of those who experience the input and do not
      develop the phenotype, while the expected fitness of those who do not experience
      the input and do not develop the phenotype should be higher than those who do not
      experience the input and do develop the phenotype. We describe ancillary
      predictions that are specific to just one of the two types of ADP and thus
      distinguish between them. 

PMID- 26203001
TI  - Variation in the link between oxygen consumption and ATP production, and its
      relevance for animal performance.
AB  - It is often assumed that an animal's metabolic rate can be estimated through
      measuring the whole-organism oxygen consumption rate. However, oxygen consumption
      alone is unlikely to be a sufficient marker of energy metabolism in many
      situations. This is due to the inherent variability in the link between oxidation
      and phosphorylation; that is, the amount of adenosine triphosphate (ATP)
      generated per molecule of oxygen consumed by mitochondria (P/O ratio). In this
      article, we describe how the P/O ratio can vary within and among individuals, and
      in response to a number of environmental parameters, including diet and
      temperature. As the P/O ratio affects the efficiency of cellular energy
      production, its variability may have significant consequences for animal
      performance, such as growth rate and reproductive output. We explore the adaptive
      significance of such variability and hypothesize that while a reduction in the
      P/O ratio is energetically costly, it may be associated with advantages in terms
      of somatic maintenance through reduced production of reactive oxygen species.
      Finally, we discuss how considering variation in mitochondrial efficiency,
      together with whole-organism oxygen consumption, can permit a better
      understanding of the relationship between energy metabolism and life history for
      studies in evolutionary ecology. 

PMID- 26203002
TI  - Structural mouthpart interaction evolved already in the earliest lineages of
      insects.
AB  - In butterflies, bees, flies and true bugs specific mouthparts are in close
      contact or even fused to enable piercing, sucking or sponging of particular food
      sources. The common phenomenon behind these mouthpart types is a complex composed
      of several consecutive mouthparts which structurally interact during food uptake.
      The single mouthparts are thus only functional in conjunction with other adjacent
      mouthparts, which is fundamentally different to biting-chewing. It is, however,
      unclear when structural mouthpart interaction (SMI) evolved since this principle
      obviously occurred multiple times independently in several extant and extinct
      winged insect groups. Here, we report a new type of SMI in two of the earliest
      wingless hexapod lineages--Diplura and Collembola. We found that the mandible and
      maxilla interact with each other via an articulatory stud at the dorsal side of
      the maxillary stipes, and they are furthermore supported by structures of the
      hypopharynx and head capsule. These interactions are crucial stabilizing elements
      during food uptake. The presence of SMI in these ancestrally wingless insects,
      and its absence in those crustacean groups probably ancestral to insects,
      indicates that SMI is a groundplan apomorphy of insects. Our results thus
      contradict the currently established view of insect mouthpart evolution that
      biting-chewing mouthparts without any form of SMI are the ancestral
      configuration. Furthermore, SMIs occur in the earliest insects in a high
      anatomical variety. SMIs in stemgroup representatives of insects may have
      triggered efficient exploitation and fast adaptation to new terrestrial food
      sources much earlier than previously supposed.

PMID- 26203003
TI  - Brain size affects the behavioural response to predators in female guppies
      (Poecilia reticulata).
AB  - Large brains are thought to result from selection for cognitive benefits, but how
      enhanced cognition leads to increased fitness remains poorly understood. One
      explanation is that increased cognitive ability results in improved monitoring
      and assessment of predator threats. Here, we use male and female guppies
      (Poecilia reticulata), artificially selected for large and small brain size, to
      provide an experimental evaluation of this hypothesis. We examined their
      behavioural response as singletons, pairs or shoals of four towards a model
      predator. Large-brained females, but not males, spent less time performing
      predator inspections, an inherently risky behaviour. Video analysis revealed that
      large-brained females were further away from the model predator when in pairs but
      that they habituated quickly towards the model when in shoals of four. Males
      stayed further away from the predator model than females but again we found no
      brain size effect in males. We conclude that differences in brain size affect the
      female predator response. Large-brained females might be able to assess risk
      better or need less sensory information to reach an accurate conclusion. Our
      results provide experimental support for the general idea that predation pressure
      is likely to be important for the evolution of brain size in prey species. 

PMID- 26203004
TI  - Adaptive genetic variation mediates bottom-up and top-down control in an aquatic
      ecosystem.
AB  - Research in eco-evolutionary dynamics and community genetics has demonstrated
      that variation within a species can have strong impacts on associated communities
      and ecosystem processes. Yet, these studies have centred around individual focal
      species and at single trophic levels, ignoring the role of phenotypic variation
      in multiple taxa within an ecosystem. Given the ubiquitous nature of local
      adaptation, and thus intraspecific variation, we sought to understand how
      combinations of intraspecific variation in multiple species within an ecosystem
      impacts its ecology. Using two species that co-occur and demonstrate adaptation
      to their natal environments, black cottonwood (Populus trichocarpa) and three
      spined stickleback (Gasterosteus aculeatus), we investigated the effects of
      intraspecific phenotypic variation on both top-down and bottom-up forces using a
      large-scale aquatic mesocosm experiment. Black cottonwood genotypes exhibit
      genetic variation in their productivity and consequently their leaf litter
      subsidies to the aquatic system, which mediates the strength of top-down effects
      from stickleback on prey abundances. Abundances of four common invertebrate prey
      species and available phosphorous, the most critically limiting nutrient in
      freshwater systems, are dictated by the interaction between genetic variation in
      cottonwood productivity and stickleback morphology. These interactive effects fit
      with ecological theory on the relationship between productivity and top-down
      control and are comparable in strength to the effects of predator addition. Our
      results illustrate that intraspecific variation, which can evolve rapidly, is an
      under-appreciated driver of community structure and ecosystem function,
      demonstrating that a multi-trophic perspective is essential to understanding the
      role of evolution in structuring ecological patterns.

PMID- 26203005
TI  - Species richness and interacting factors control invasibility of a marine
      community.
AB  - Anthropogenic vectors have moved marine species around the world leading to
      increased invasions and expanded species' ranges. The biotic resistance
      hypothesis of Elton (in The ecology of invasions by animals and plants, 1958)
      predicts that more diverse communities should have greater resistance to
      invasions, but experiments have been equivocal. We hypothesized that species
      richness interacts with other factors to determine experimental outcomes. We
      manipulated species richness, species composition (native and introduced) and
      availability of bare space in invertebrate assemblages in a marina in Monterey,
      CA. Increased species richness significantly interacted with both initial cover
      of native species and of all organisms to collectively decrease recruitment.
      Although native species decreased recruitment, introduced species had a similar
      effect, and we concluded that biotic resistance is conferred by total species
      richness. We suggest that contradictory conclusions in previous studies about the
      role of diversity in regulating invasions reflect uncontrolled variables in those
      experiments that modified the effect of species richness. Our results suggest
      that patches of low diversity and abundance may facilitate invasions, and that
      such patches, once colonized by non-indigenous species, can resist both native
      and non-indigenous species recruitment. 

PMID- 26203006
TI  - New insights into carbon acquisition and exchanges within the coral
      dinoflagellate symbiosis under NH4+ and NO3- supply.
AB  - Anthropogenic nutrient enrichment affects the biogeochemical cycles and nutrient
      stoichiometry of coastal ecosystems and is often associated with coral reef
      decline. However, the mechanisms by which dissolved inorganic nutrients, and
      especially nitrogen forms (ammonium versus nitrate) can disturb the association
      between corals and their symbiotic algae are subject to controversial debate.
      Here, we investigated the coral response to varying N : P ratios, with nitrate or
      ammonium as a nitrogen source. We showed significant differences in the carbon
      acquisition by the symbionts and its allocation within the symbiosis according to
      nutrient abundance, type and stoichiometry. In particular, under low phosphate
      concentration (0.05 uM), a 3 uM nitrate enrichment induced a significant decrease
      in carbon fixation rate and low values of carbon translocation, compared with
      control conditions (N : P = 0.5 : 0.05), while these processes were significantly
      enhanced when nitrate was replaced by ammonium. A combined enrichment in ammonium
      and phosphorus (N : P = 3 : 1) induced a shift in nutrient allocation to the
      symbionts, at the detriment of the host. Altogether, these results shed light
      into the effect of nutrient enrichment on reef corals. More broadly, they improve
      our understanding of the consequences of nutrient loading on reef ecosystems,
      which is urgently required to refine risk management strategies.

PMID- 26203008
TI  - Tuned range separated hybrid functionals for solvated low bandgap oligomers.
AB  - The description of charge transfer excitations has long been a challenge to time
      dependent density functional theory. The recently developed concept of "optimally
      tuned range separated hybrid (OT-RSH) functionals" has proven to describe charge
      transfer excitations accurately in many cases. However, describing solvated or
      embedded systems is yet a challenge. This challenge is not only computational but
      also conceptual, because the tuning requires identifying a specific orbital,
      typically the highest occupied one of the molecule under study. For solvated
      molecules, this orbital may be delocalized over the solvent. We here demonstrate
      that one way of overcoming this problem is to use a locally projected self
      consistent field diagonalization on an absolutely localized molecular orbital
      expansion. We employ this approach to determine ionization energies and the
      optical gap of solvated oligothiophenes, i.e., paradigm low gap systems that are
      of relevance in organic electronics. Dioxane solvent molecules are explicitly
      represented in our calculations, and the ambiguities of straightforward parameter
      tuning in solution are elucidated. We show that a consistent estimate of the
      optimal range separated parameter (omega) at the limit of bulk solvation can be
      obtained by gradually extending the solvated system. In particular, omega is
      influenced by the solvent beyond the first coordination sphere. For determining
      ionization energies, a considerable number of solvent molecules on the first
      solvation shell must be taken into account. We demonstrate that accurately
      calculating optical gaps of solvated systems using OT-RSH can be done in three
      steps: (i) including the chemical environment when determining the range
      separation parameter, (ii) taking into account the screening due to the solvent,
      and (iii) using realistic molecular geometries. 

PMID- 26203007
TI  - Economic development, climate and values: making policy.
AB  - The two defining challenges of this century are overcoming poverty and managing
      the risks of climate change. Over the past 10 years, we have learned much about
      how to tackle them together from ideas on economic development and public policy.
      My own work in these areas over four decades as an academic and as a policy
      adviser in universities and international financial institutions has focused on
      how the investment environment and the empowerment of people can change lives and
      livelihoods. The application of insights from economic development and public
      policy to climate change requires rigorous analysis of issues such as
      discounting, modelling the risks of unmanaged climate change, climate policy
      targets and estimates of the costs of mitigation. The latest research and results
      show that the case for avoiding the risks of dangerous climate change through the
      transition to low-carbon economic development and growth is still stronger than
      when the Stern Review was published. This is partly because of evidence that some
      of the impacts of climate change are happening more quickly than originally
      expected, and because of remarkable advances in technologies, such as solar
      power. Nevertheless, significant hurdles remain in securing the international
      cooperation required to avoid dangerous climate change, not least because of
      disagreements and misunderstandings about key issues, such as ethics and equity. 

PMID- 26203009
TI  - Non-adiabatic current densities, transitions, and power absorbed by a molecule in
      a time-dependent electromagnetic field.
AB  - The energy of a molecule subject to a time-dependent perturbation separates
      completely into adiabatic and non-adiabatic terms, where the adiabatic term
      reflects the adjustment of the ground state to the perturbation, while the non
      adiabatic term accounts for the transition energy [A. Mandal and K. L. C. Hunt,
      J. Chem. Phys. 137, 164109 (2012)]. For a molecule perturbed by a time-dependent
      electromagnetic field, in this work, we show that the expectation value of the
      power absorbed by the molecule is equal to the time rate of change of the non
      adiabatic term in the energy. The non-adiabatic term is given by the transition
      probability to an excited state k, multiplied by the transition energy from the
      ground state to k, and then summed over the excited states. The expectation value
      of the power absorbed by the molecule is derived from the integral over space of
      the scalar product of the applied electric field and the non-adiabatic current
      density induced in the molecule by the field. No net power is absorbed due to the
      action of the applied electric field on the adiabatic current density. The work
      done on the molecule by the applied field is the time integral of the power
      absorbed. The result established here shows that work done on the molecule by the
      applied field changes the populations of the molecular states. 

PMID- 26203010
TI  - Roothaan's approach to solve the Hartree-Fock equations for atoms confined by
      soft walls: Basis set with correct asymptotic behavior.
AB  - In this report, we use a new basis set for Hartree-Fock calculations related to
      many-electron atoms confined by soft walls. One- and two-electron integrals were
      programmed in a code based in parallel programming techniques. The results
      obtained with this proposal for hydrogen and helium atoms were contrasted with
      other proposals to study just one and two electron confined atoms, where we have
      reproduced or improved the results previously reported. Usually, an atom enclosed
      by hard walls has been used as a model to study confinement effects on orbital
      energies, the main conclusion reached by this model is that orbital energies
      always go up when the confinement radius is reduced. However, such an observation
      is not necessarily valid for atoms confined by penetrable walls. The main reason
      behind this result is that for atoms with large polarizability, like beryllium or
      potassium, external orbitals are delocalized when the confinement is imposed and
      consequently, the internal orbitals behave as if they were in an ionized atom.
      Naturally, the shell structure of these atoms is modified drastically when they
      are confined. The delocalization was an argument proposed for atoms confined by
      hard walls, but it was never verified. In this work, the confinement imposed by
      soft walls allows to analyze the delocalization concept in many-electron atoms. 

PMID- 26203011
TI  - Towards quantifying the role of exact exchange in predictions of transition metal
      complex properties.
AB  - We estimate the prediction sensitivity with respect to Hartree-Fock exchange in
      approximate density functionals for representative Fe(II) and Fe(III) octahedral
      complexes. Based on the observation that the range of parameters spanned by the
      most widely employed functionals is relatively narrow, we compute electronic
      structure property and spin-state orderings across a relatively broad range of
      Hartree-Fock exchange (0%-50%) ratios. For the entire range considered, we
      consistently observe linear relationships between spin-state ordering that differ
      only based on the element of the direct ligand and thus may be broadly employed
      as measures of functional sensitivity in predictions of organometallic compounds.
      The role Hartree-Fock exchange in hybrid functionals is often assumed to play is
      to correct self-interaction error-driven electron delocalization (e.g., from
      transition metal centers to neighboring ligands). Surprisingly, we instead
      observe that increasing Hartree-Fock exchange reduces charge on iron centers,
      corresponding to effective delocalization of charge to ligands, thus challenging
      notions of the role of Hartree-Fock exchange in shifting predictions of spin
      state ordering. 

PMID- 26203012
TI  - Density-matrix renormalization group algorithm with multi-level active space.
AB  - The density-matrix renormalization group (DMRG) method, which can deal with a
      large active space composed of tens of orbitals, is nowadays widely used as an
      efficient addition to traditional complete active space (CAS)-based approaches.
      In this paper, we present the DMRG algorithm with a multi-level (ML) control of
      the active space based on chemical intuition-based hierarchical orbital ordering,
      which is called as ML-DMRG with its self-consistent field (SCF) variant ML-DMRG
      SCF. Ground and excited state calculations of H2O, N2, indole, and Cr2 with
      comparisons to DMRG references using fixed number of kept states (M) illustrate
      that ML-type DMRG calculations can obtain noticeable efficiency gains. It is also
      shown that the orbital re-ordering based on hierarchical multiple active
      subspaces may be beneficial for reducing computational time for not only ML-DMRG
      calculations but also DMRG ones with fixed M values. 

PMID- 26203013
TI  - An efficient and accurate approximation to time-dependent density functional
      theory for systems of weakly coupled monomers.
AB  - A novel formulation of time-dependent density functional theory (TDDFT) is
      derived, based on non-orthogonal, absolutely-localized molecular orbitals
      (ALMOs). We call this approach TDDFT(MI), in reference to ALMO-based methods for
      describing molecular interactions (MI) that have been developed for ground-state
      applications. TDDFT(MI) is intended for efficient excited-state calculations in
      systems composed of multiple, weakly interacting chromophores. The efficiency is
      based upon (1) a local excitation approximation; (2) monomer-based, singly
      excited basis states; (3) an efficient localization procedure; and (4) a one-step
      Davidson method to solve the TDDFT(MI) working equation. We apply this
      methodology to study molecular dimers, water clusters, solvated chromophores, and
      aggregates of naphthalene diimide that form the building blocks of self
      assembling organic nanotubes. Absolute errors of 0.1-0.3 eV with respect to
      supersystem methods are achievable for these systems, especially for cases
      involving an excited chromophore that is weakly coupled to several explicit
      solvent molecules. Excited-state calculations in an aggregate of nine naphthalene
      diimide monomers are ~40 times faster than traditional TDDFT calculations. 

PMID- 26203014
TI  - Application of quasi-degenerate perturbation theory to the calculation of
      rotational energy levels of methane vibrational polyads.
AB  - In previous works, we have introduced an alternative perturbation scheme to find
      approximate solutions of the spectral problem for the rotation-vibration
      molecular Hamiltonian. An important feature of our approach is that the zero
      order Hamiltonian is the direct product of a purely vibrational Hamiltonian with
      the identity on the rotational degrees of freedom. The convergence of our method
      for the methane vibrational ground state was very satisfactory and our
      predictions were quantitative. In the present article, we provide further details
      on the implementation of the method in the degenerate and quasi-degenerate cases.
      The quasi-degenerate version of the method is tested on excited polyads of
      methane, and the results are assessed with respect to a variational treatment.
      The optimal choice of the size of quasi-degenerate spaces is determined by a
      trade-off between speed of convergence of the perturbation series and the
      computational effort to obtain the effective super-Hamiltonian. 

PMID- 26203015
TI  - Sparse maps-A systematic infrastructure for reduced-scaling electronic structure
      methods. I. An efficient and simple linear scaling local MP2 method that uses an
      intermediate basis of pair natural orbitals.
AB  - In this work, a systematic infrastructure is described that formalizes concepts
      implicit in previous work and greatly simplifies computer implementation of
      reduced-scaling electronic structure methods. The key concept is sparse
      representation of tensors using chains of sparse maps between two index sets.
      Sparse map representation can be viewed as a generalization of compressed sparse
      row, a common representation of a sparse matrix, to tensor data. By combining few
      elementary operations on sparse maps (inversion, chaining, intersection, etc.),
      complex algorithms can be developed, illustrated here by a linear-scaling
      transformation of three-center Coulomb integrals based on our compact code
      library that implements sparse maps and operations on them. The sparsity of the
      three-center integrals arises from spatial locality of the basis functions and
      domain density fitting approximation. A novel feature of our approach is the use
      of differential overlap integrals computed in linear-scaling fashion for
      screening products of basis functions. Finally, a robust linear scaling domain
      based local pair natural orbital second-order Moller-Plesset (DLPNO-MP2) method
      is described based on the sparse map infrastructure that only depends on a
      minimal number of cutoff parameters that can be systematically tightened to
      approach 100% of the canonical MP2 correlation energy. With default truncation
      thresholds, DLPNO-MP2 recovers more than 99.9% of the canonical resolution of the
      identity MP2 (RI-MP2) energy while still showing a very early crossover with
      respect to the computational effort. Based on extensive benchmark calculations,
      relative energies are reproduced with an error of typically <0.2 kcal/mol. The
      efficiency of the local MP2 (LMP2) method can be drastically improved by carrying
      out the LMP2 iterations in a basis of pair natural orbitals. While the present
      work focuses on local electron correlation, it is of much broader applicability
      to computation with sparse tensors in quantum chemistry and beyond. 

PMID- 26203016
TI  - Efficient maximum likelihood parameterization of continuous-time Markov
      processes.
AB  - Continuous-time Markov processes over finite state-spaces are widely used to
      model dynamical processes in many fields of natural and social science. Here, we
      introduce a maximum likelihood estimator for constructing such models from data
      observed at a finite time interval. This estimator is dramatically more efficient
      than prior approaches, enables the calculation of deterministic confidence
      intervals in all model parameters, and can easily enforce important physical
      constraints on the models such as detailed balance. We demonstrate and discuss
      the advantages of these models over existing discrete-time Markov models for the
      analysis of molecular dynamics simulations. 

PMID- 26203017
TI  - On the use of a weak-coupling thermostat in replica-exchange molecular dynamics
      simulations.
AB  - In a molecular dynamics (MD) simulation, various thermostat algorithms, including
      Langevin dynamics (LD), Nose-Hoover (NH), and weak-coupling (WC) thermostats, can
      be used to keep the simulation temperature constant. A canonical ensemble is
      generated by the use of LD and NH, while the nature of the ensemble produced by
      WC has not yet been identified. A few years ago, it was shown that when using a
      WC thermostat with particular values of the temperature coupling time for liquid
      water at ambient temperature and pressure, the distribution of the potential
      energy is less wide than the canonical one. This led to an artifact in
      temperature replica-exchange molecular dynamics (T-REMD) simulations in which the
      potential energy distributions appear not to be equal to the ones of standard MD
      simulations. In this paper, we re-investigate this problem. We show that this
      artifact is probably due to the ensemble generated by WC being incompatible with
      the T-REMD replica-exchange criterion, which assumes a canonical configurational
      ensemble. We also show, however, that this artifact can be reduced or even
      eliminated by particular choices of the temperature coupling time of WC and the
      replica-exchange time period of T-REMD, i.e., when the temperature coupling time
      is chosen very close to the MD time step or when the exchange time period is
      chosen large enough. An attempt to develop a T-REMD replica-exchange criterion
      which is likely to be more compatible with the WC configurational ensemble is
      reported. Furthermore, an exchange criterion which is compatible with a
      microcanonical ensemble is used in total energy REMD simulations. 

PMID- 26203018
TI  - Leading order nonadiabatic corrections to rovibrational levels of H2, D2, and T2.
AB  - An efficient computational approach to nonadiabatic effects in the hydrogen
      molecule (H2, D2, and T2) is presented. The electronic wave function is expanded
      in the James-Coolidge basis set, which enables obtaining a very high accuracy of
      nonadiabatic potentials. A single point convergence of the potentials with
      growing size of the basis set reveals a relative accuracy ranging from 10(-8) to
      10(-13). An estimated accuracy of the leading nonadiabatic correction to the
      rovibrational energy levels is of the order of 10(-7) cm(-1). After a significant
      increase in the accuracy of the Born-Oppenheimer and adiabatic calculations, the
      nonadiabatic results presented in this report constitute another step towards
      highly accurate theoretical description of the hydrogen molecule. 

PMID- 26203020
TI  - Development of single-channel heterodyne-detected sum frequency generation
      spectroscopy and its application to the water/vapor interface.
AB  - Single-channel heterodyne-detected sum frequency generation (HD-SFG) spectroscopy
      for selectively measuring vibrational spectra of liquid interfaces is presented.
      This new methodology is based on optical interference between sum frequency
      signal light from a sample interface and phase-controlled local oscillator light.
      In single-channel HD-SFG, interferometric and spectrometric measurements are
      simultaneously carried out with an input IR laser scanned in a certain wavenumber
      range, which results in a less task than existing phase-sensitive sum frequency
      spectroscopy. The real and imaginary parts of second-order nonlinear optical
      susceptibility (chi((2))) of interfaces are separately obtained with spectral
      resolution as high as 4 cm(-1) that is approximately six times better than
      existing multiplex HD-SFG. In this paper, the experimental procedure and
      theoretical background of single-channel HD-SFG are explicated, and its
      application to the water/vapor interface is demonstrated, putting emphasis on the
      importance of a standard for the complex phase of chi((2)). 

PMID- 26203019
TI  - Selective excitation enables assignment of proton resonances and (1)H-(1)H
      distance measurement in ultrafast magic angle spinning solid state NMR
      spectroscopy.
AB  - Remarkable developments in ultrafast magic angle spinning (MAS) solid-state NMR
      spectroscopy enabled proton-based high-resolution multidimensional experiments on
      solids. To fully utilize the benefits rendered by proton-based ultrafast MAS
      experiments, assignment of (1)H resonances becomes absolutely necessary. Herein,
      we propose an approach to identify different proton peaks by using dipolar
      coupled heteronuclei such as (13)C or (15)N. In this method, after the initial
      preparation of proton magnetization and cross-polarization to (13)C nuclei,
      transverse magnetization of desired (13)C nuclei is selectively prepared by using
      DANTE (Delays Alternating with Nutations for Tailored Excitation) sequence and
      then, it is transferred to bonded protons with a short-contact-time cross
      polarization. Our experimental results demonstrate that protons bonded to
      specific (13)C atoms can be identified and overlapping proton peaks can also be
      assigned. In contrast to the regular 2D HETCOR experiment, only a few 1D
      experiments are required for the complete assignment of peaks in the proton
      spectrum. Furthermore, the finite-pulse radio frequency driven recoupling
      sequence could be incorporated right after the selection of specific proton
      signals to monitor the intensity buildup for other proton signals. This enables
      the extraction of (1)H-(1)H distances between different pairs of protons.
      Therefore, we believe that the proposed method will greatly aid in fast
      assignment of peaks in proton spectra and will be useful in the development of
      proton-based multi-dimensional solid-state NMR experiments to study atomic-level
      resolution structure and dynamics of solids. 

PMID- 26203021
TI  - Molecular reorganization of selected quinoline derivatives in the ground and
      excited states-Investigations via static DFT.
AB  - Quinoline derivatives are interesting objects to study internal reorganizations
      due to the observed excited-state-induced intramolecular proton transfer (ESIPT).
      Here, we report on computations for selected 12 quinoline derivatives possessing
      three kinds of intramolecular hydrogen bonds. Density functional theory was
      employed for the current investigations. The metric and electronic structure
      simulations were performed for the ground state and first excited singlet and
      triplet states. The computed potential energy profiles do not show a spontaneous
      proton transfer in the ground state, whereas excited states exhibit this
      phenomenon. Atoms in Molecules (AIM) theory was applied to study the nature of
      hydrogen bonding, whereas Harmonic Oscillator Model of aromaticity index (HOMA)
      provided data of aromaticity evolution as a derivative of the bridge proton
      position. The AIM-based topological analysis confirmed the presence of the
      intramolecular hydrogen bonding. In addition, using the theory, we were able to
      provide a quantitative illustration of bonding transformation: from covalent to
      the hydrogen. On the basis of HOMA analysis, we showed that the aromaticity of
      both rings is dependent on the location of the bridge proton. Further, the
      computed results were compared with experimental data available. Finally, ESIPT
      occurrence was compared for the three investigated kinds of hydrogen bridges, and
      competition between two bridges in one molecule was studied. 

PMID- 26203022
TI  - Dynamics of solvation and desolvation of rubidium attached to He nanodroplets.
AB  - The real-time dynamics of photoexcited and photoionized rubidium (Rb) atoms
      attached to helium (He) nanodroplets is studied by femtosecond pump-probe mass
      spectrometry. While excited Rb atoms in the perturbed 6p-state (Rb*) desorb off
      the He droplets, Rb(+) photoions tend to sink into the droplet interior when
      created near the droplet surface. The transition from Rb(+) solvation to full Rb*
      desorption is found to occur at a delay time tau ~ 600 fs for Rb* in the 6pSigma
      state and tau ~ 1200 fs for the 6pPi-state. Rb(+)He ions are found to be created
      by directly exciting bound Rb*He exciplex states as well as by populating bound
      Rb(+)He-states in a photoassociative ionization process.

PMID- 26203023
TI  - Characterization and reactivity of the weakly bound complexes of the [H, N, S](-)
      anionic system with astrophysical and biological implications.
AB  - We investigate the lowest electronic states of doublet and quartet spin
      multiplicity states of HNS(-) and HSN(-) together with their parent neutral
      triatomic molecules. Computations were performed using highly accurate ab initio
      methods with a large basis set. One-dimensional cuts of the full-dimensional
      potential energy surfaces (PESs) along the interatomic distances and bending
      angle are presented for each isomer. Results show that the ground anionic states
      are stable with respect to the electron detachment process and that the long
      range parts of the PESs correlating to the SH(-) + N, SN(-) + H, SN + H(-), NH +
      S(-), and NH(-) + S are bound. In addition, we predict the existence of long
      lived weakly bound anionic complexes that can be formed after cold collisions
      between SN(-) and H or SH(-) and N. The implications for the reactivity of these
      species are discussed; specifically, it is shown that the reactions involving SH(
      ), SN(-), and NH(-) lead either to the formation of HNS(-) or HSN(-) in their
      electronic ground states or to autodetachment processes. Thus, providing an
      explanation for why the anions, SH(-), SN(-), and NH(-), have limiting
      detectability in astrophysical media despite the observation of their
      corresponding neutral species. In a biological context, we suggest that HSN(-)
      and HNS(-) should be incorporated into H2S-assisted heme-catalyzed reduction
      mechanism of nitrites in vivo. 

PMID- 26203024
TI  - High-resolution vacuum-ultraviolet photoabsorption spectra of 1-butyne and 2
      butyne.
AB  - The absolute photoabsorption cross sections of 1- and 2-butyne have been recorded
      at high resolution by using the vacuum-ultraviolet Fourier-Transform spectrometer
      at the SOLEIL Synchrotron. Both spectra show more resolved structure than
      previously observed, especially in the case of 2-butyne. In this work, we assess
      the potential importance of Rydberg states with higher values of orbital angular
      momentum, l, than are typically observed in photoabsorption experiments from
      ground state molecules. We show how the character of the highest occupied
      molecular orbitals in 1- and 2-butyne suggests the potential importance of
      transitions to such high-l (l = 3 and 4) Rydberg states. Furthermore, we use
      theoretical calculations of the partial wave composition of the absorption cross
      section just above the ionization threshold and the principle of continuity of
      oscillator strength through an ionization threshold to support this conclusion.
      The new absolute photoabsorption cross sections are discussed in light of these
      arguments, and the results are consistent with the expectations. This type of
      argument should be valuable for assessing the potential importance of different
      Rydberg series when sufficiently accurate direct quantum chemical calculations
      are difficult, for example, in the n >= 5 manifolds of excited states of larger
      molecules. 

PMID- 26203025
TI  - Low-lying electronic structure of EuH, EuOH, and EuO neutrals and anions
      determined by anion photoelectron spectroscopy and DFT calculations.
AB  - The anion photoelectron (PE) spectra of EuH(-) and the PE spectrum of overlapping
      EuOH(-) and EuO(-) anions are presented and analyzed with supporting results from
      density functional theory calculations on the various anions and neutrals.
      Results point to ionically bound, high-spin species. EuH and EuOH anions and
      neutrals exhibit analogous electronic structures: Transitions from (8)Sigma(-)
      anion ground states arising from the 4f(7)sigma(6s)(2) superconfiguration to the
      close-lying neutral (9)Sigma(-) and (7)Sigma(-) states arising from the
      4f(7)sigma(6s) superconfiguration are observed spaced by an energy interval
      similar to the free Eu(+) [4f(7)6s] (9)S - (7)S splitting. The electron
      affinities (EAs) of EuH and EuOH are determined to be 0.771 +/- 0.009 eV and
      0.700 +/- 0.011 eV, respectively. Analysis of spectroscopic features attributed
      to EuO(-) photodetachment is complicated by the likely presence of two
      energetically competitive electronic states of EuO(-) populating the ion beam.
      However, based on the calculated relative energies of the close-lying anion
      states arising from the 4f(7)sigma(6s) and 4f(6)sigma(6s)(2) configurations and
      the relative energies of the one-electron accessible 4f(7) and 4f(6)sigma(6s)
      neutral states based on ligand-field theory [M. Dulick, E. Murad, and R. F.
      Barrow, J. Chem. Phys. 85, 385 (1986)], the remaining features are consistent
      with the 4f(6)sigma(6s)(2) (7)Sigma(-) and 4f(7)sigma(6s) (7)Sigma(-) anion
      states lying very close in energy (the former was calculated to be 0.15 eV lower
      in energy than the latter), though the true anion ground state and neutral EA
      could not be established unambiguously. Calculations on the various EuO anion and
      neutral states suggest 4f-orbital overlap with 2p orbitals in species with 4f(6)
      occupancy.

PMID- 26203026
TI  - Stepwise vs concerted excited state tautomerization of 2-hydroxypyridine: Ammonia
      dimer wire mediated hydrogen/proton transfer.
AB  - The stepwise and concerted excited state intermolecular proton transfer (PT) and
      hydrogen transfer (HT) reactions in 2-hydroxypyridine-(NH3)2 complex in the gas
      phase under Cs symmetry constraint and without any symmetry constraints were
      performed using quantum chemical calculations. It shows that upon excitation, the
      hydrogen bonded in 2HP-(NH3)2 cluster facilitates the releasing of both hydrogen
      and proton transfer reactions along ammonia wire leading to the formation of the
      2-pyridone tautomer. For the stepwise mechanism, it has been found that the
      proton and the hydrogen may transfer consecutively. These processes are
      distinguished from each other through charge translocation analysis and the
      coupling between the motion of the proton and the electron density distribution
      along ammonia wire. For the complex under Cs symmetry, the excited state HT
      occurs on the A"((1)pisigma*) and A'((1)nsigma*) states over two accessible
      energy barriers along reaction coordinates, and excited state PT proceeds mainly
      through the A'((1)pipi*) and A"((1)npi*) potential energy surfaces. For the
      unconstrained complex, potential energy profiles show two (1)pipi*-(1)pisigma*
      conical intersections along enol -> keto reaction path indicating that proton and
      H atom are localized, respectively, on the first and second ammonia of the wire.
      Moreover, the concerted excited state PT is competitive to take place with the
      stepwise process, because it proceeds over low barriers of 0.14 eV and 0.11 eV
      with respect to the Franck-Condon excitation of enol tautomer, respectively,
      under Cs symmetry and without any symmetry constraints. These barriers can be
      probably overcome through tunneling effect.

PMID- 26203027
TI  - Energy transfer upon collision of selectively excited CO2 molecules: State-to
      state cross sections and probabilities for modeling of atmospheres and gaseous
      flows.
AB  - Carbon dioxide molecules can store and release tens of kcal/mol upon collisions,
      and such an energy transfer strongly influences the energy disposal and the
      chemical processes in gases under the extreme conditions typical of plasmas and
      hypersonic flows. Moreover, the energy transfer involving CO2 characterizes the
      global dynamics of the Earth-atmosphere system and the energy balance of other
      planetary atmospheres. Contemporary developments in kinetic modeling of gaseous
      mixtures are connected to progress in the description of the energy transfer,
      and, in particular, the attempts to include non-equilibrium effects require to
      consider state-specific energy exchanges. A systematic study of the state-to
      state vibrational energy transfer in CO2 + CO2 collisions is the focus of the
      present work, aided by a theoretical and computational tool based on
      quasiclassical trajectory simulations and an accurate full-dimension model of the
      intermolecular interactions. In this model, the accuracy of the description of
      the intermolecular forces (that determine the probability of energy transfer in
      molecular collisions) is enhanced by explicit account of the specific effects of
      the distortion of the CO2 structure due to vibrations. Results show that these
      effects are important for the energy transfer probabilities. Moreover, the role
      of rotational and vibrational degrees of freedom is found to be dominant in the
      energy exchange, while the average contribution of translations, under the
      temperature and energy conditions considered, is negligible. Remarkable is the
      fact that the intramolecular energy transfer only involves stretching and
      bending, unless one of the colliding molecules has an initial symmetric
      stretching quantum number greater than a threshold value estimated to be equal to
      7. 

PMID- 26203028
TI  - Influences of the propyl group on the van der Waals structures of 4-propylaniline
      complexes with one and two argon atoms studied by electronic and cationic
      spectroscopy.
AB  - 4-propylaniline complexes with one and two argon atoms formed in the molecular
      beam were studied in the first excited electronic state, S1, using resonance
      enhanced two-photon ionization spectroscopy and in the cation ground state, D0,
      using mass analyzed threshold ionization spectroscopy. The combination of
      electronic and cationic spectra of the clusters allows two conformations to be
      identified in both aniline-Ar1 and aniline-Ar2, which are assigned to either the
      gauche configuration or anti-configuration of 4-propylaniline. The gauche isomer
      exhibits complex bands shifted 29 cm(-1) and 89 cm(-1) from the S1 origin bands
      and 83 cm(-1) and 148 cm(-1) from the ionization potential assigned to the Ar1
      and Ar2 complexes, respectively. For the anti-rotamer, the corresponding shifts
      actually become nearly additive, 53 cm(-1) and 109 cm(-1) for the S1 origin
      bands, and 61 cm(-1) and 125 cm(-1) for the ionization potentials. Ab initio
      calculations provide insights into the influences of the propyl and amino groups
      on the positions of the argon atoms within the clusters. In addition, the binding
      energy of one argon with the gauche isomer of 4-propylaniline has been measured
      to be 550 +/- 5 cm(-1) in the D0 state, 496 +/- 5 cm(-1) in the S1 state, and 467
      +/- 5 cm(-1) in the neutral ground state, S0. 

PMID- 26203029
TI  - Solvent-dependent intramolecular charge transfer delocalization/localization in
      multibranched push-pull chromophores.
AB  - The effect of the solvent polarity on excitation delocalization/localization in
      multibranched push-pull chromophores has been thoroughly explored by combining
      steady state absorption and fluorescence, as well as femtosecond transient
      spectral measurements. We found that the excited-state relaxations of the push
      pull chromophores are highly dependent on both solvent polarity and the polar
      degree of the excited intramolecular charge transfer states. The symmetry of
      multibranched chromophores is preserved in less polar solvents, leading to
      excitation delocalization over all of the branches because of the negligible
      solvent reaction field. In contrast, symmetry is broken for multibranched
      chromophores in more polar solvents because of intense solvent reaction field,
      and the excitation is consequently localized on one of the dipolar molecular
      branches. The results provide a fundamental understanding of solvent-dependent
      excitation delocalization/localization properties of the multibranched
      chromophores for the potential applications in nonlinear optics and energy
      harvesting applications. 

PMID- 26203030
TI  - Polyamorphism in tetrahedral substances: Similarities between silicon and ice.
AB  - Tetrahedral substances, such as silicon, water, germanium, and silica, share
      various unusual phase behaviors. Among them, the so-called polyamorphism, i.e.,
      the existence of more than one amorphous form, has been intensively investigated
      in the last three decades. In this work, we study the metastable relations
      between amorphous states of silicon in a wide range of pressures, using Monte
      Carlo simulations. Our results indicate that the two amorphous forms of silicon
      at high pressures, the high density amorphous (HDA) and the very high density
      amorphous (VHDA), can be decompressed from high pressure (~20 GPa) down to the
      tensile regime, where both convert into the same low density amorphous. Such
      behavior is also observed in ice. While at high pressure (~20 GPa), HDA is less
      stable than VHDA, at the pressure of 10 GPa both forms exhibit similar stability.
      On the other hand, at much lower pressure (~5 GPa), HDA and VHDA are no longer
      the most stable forms, and, upon isobaric annealing, an even less dense form of
      amorphous silicon emerges, the expanded high density amorphous, again in close
      similarity to what occurs in ice. 

PMID- 26203031
TI  - The photoexcitation of crystalline ice and amorphous solid water: A molecular
      dynamics study of outcomes at 11 K and 125 K.
AB  - Photoexcitation of crystalline ice Ih and amorphous solid water at 7-9 eV is
      examined using molecular dynamics simulations and a fully flexible water model.
      The probabilities of photofragment desorption, trapping, and recombination are
      examined for crystalline ice at 11 K and at 125 K and for amorphous solid water
      at 11 K. For 11 K crystalline ice, a fully rigid water model is also employed for
      comparison. The kinetic energy of desorbed H atoms and the distance travelled by
      trapped fragments are correlated to the location and the local environment of the
      photoexcited water molecule. In all cases, H atom desorption is found to be the
      most likely outcome in the top bilayer while trapping of all photofragments is
      most probable deeper in the solid where the likelihood for recombination of the
      fragments into H2O molecules also rises. Trajectory analysis indicates that the
      local hydrogen bonding network in amorphous solid water is more easily distorted
      by a photodissociation event compared to crystalline ice. Also, simulations
      indicate that desorption of OH radicals and H2O molecules are more probable in
      amorphous solid water. The kinetic energy distributions for desorbed H atoms show
      a peak at high energy in crystalline ice, arising from photoexcited water
      molecules in the top monolayer. This peak is less pronounced in amorphous solid
      water. H atoms that are trapped may be displaced by up to ~10 water cages, but
      migrate on average 3 water cages. Trapped OH fragments tend to stay near the
      original solvent cage. 

PMID- 26203032
TI  - A systematic study of segregation for Zn(x)Bi(1-x) liquid binary alloys.
AB  - We have investigated the segregating properties of Zn(x)Bi(1-x) liquid binary
      alloys through the thermodynamic route that involves both energy of mixing and
      entropy of mixing. The perturbation approach is used for effective numerical
      calculations. Results of our calculations agree well with corresponding
      experimental data for energy and entropy of mixing in the mixed state. The final
      prediction of segregating properties such as critical concentration and critical
      temperature also matches reasonably well with experimental data. Most
      importantly, both energy of mixing and entropy of mixing have produced almost
      same values for critical concentration and critical temperature of segregation
      and thus confirm the reliability of the present approach.

PMID- 26203033
TI  - Origin of structural analogies and differences between the atomic structures of
      GeSe4 and GeS4 glasses: A first principles study.
AB  - First-principles molecular dynamics simulations based on density functional
      theory are employed for a comparative study of structural and bonding properties
      of two stoichiometrically identical chalcogenide glasses, GeSe4 and GeS4. Two
      periodic cells of 120 and 480 atoms are adopted. Both glasses feature a
      coexistence of Ge-centered tetrahedra and Se(S) homopolar connections. Results
      obtained for N = 480 indicate substantial differences at the level of the Se(S)
      environment, since Ge-Se-Se connections are more frequent than the corresponding
      Ge-S-S ones. The presence of a more prominent first sharp diffraction peak in the
      total neutron structure factor of glassy GeS4 is rationalized in terms of a
      higher number of large size rings, accounting for extended Ge-Se correlations.
      Both the electronic density of states and appropriate electronic localization
      tools provide evidence of a higher ionic character of Ge-S bonds when compared to
      Ge-Se bonds. An interesting byproduct of these investigations is the occurrence
      of discernible size effects that affect structural motifs involving next nearest
      neighbor distances, when 120 or 480 atoms are used. 

PMID- 26203034
TI  - Shear-induced breaking of cages in colloidal glasses: Scattering experiments and
      mode coupling theory.
AB  - We employ x-ray scattering on sheared colloidal suspensions and mode coupling
      theory to study structure factor distortions of glass-forming systems under
      shear. We find a transition from quadrupolar elastic distortion at small strains
      to quadrupolar and hexadecupolar modes in the stationary state. The latter are
      interpreted as signatures of plastic rearrangements in homogeneous, thermalized
      systems. From their transient evolution with strain, we identify characteristic
      strain and length-scale values where these plastic rearrangements dominate. This
      characteristic strain coincides with the maximum of the shear stress versus
      strain curve, indicating the proliferation of plastic flow. The hexadecupolar
      modes dominate at the wavevector of the principal peak of the equilibrium
      structure factor that is related to the cage-effect in mode coupling theory. We
      hence identify the structural signature of plastic flow of glasses. 

PMID- 26203035
TI  - Pair correlations in classical crystals: The shortest-graph method.
AB  - The shortest-graph method is applied to calculate the pair correlation functions
      of crystals. The method is based on the representation of individual correlation
      peaks by the Gaussian functions, summed along the shortest graph connecting the
      two given points. The analytical expressions for the Gaussian parameters are
      derived for two- and three-dimensional crystals. The obtained results are
      compared with the pair correlation functions deduced from the molecular dynamics
      simulations of Yukawa, inverse-power law, Weeks-Chandler-Andersen, and Lennard
      Jones crystals. By calculating the Helmholtz free energy, it is shown that the
      method is particularly accurate for soft interparticle interactions and for low
      temperatures, i.e., when the anharmonicity effects are insignificant. The
      accuracy of the method is further demonstrated by deriving the solid-solid
      transition line for Yukawa crystals, and the compressibility for inverse-power
      law crystals. 

PMID- 26203036
TI  - Identifying site-dependent effects of an extra Co atom on electronic states of
      single Co-phthalocyanine molecule.
AB  - We investigate the modification of electronic properties of single cobalt
      phthalocyanine (CoPc) molecule by an extra Co atom co-adsorbed on Au (111)
      surface using scanning tunneling microscopy (STM), joint with density functional
      theory (DFT) calculations. By manipulating CoPc molecules using the STM tip to
      contact individually adsorbed Co atom, two types of relatively stable complexes
      can be formed, denoted as CoPc-Co(I) and CoPc-Co(II). In CoPc-Co(I), the Co atom
      is at an intramolecular site close to aza-N atom of CoPc, which induces
      significant modifications of the electronic states of CoPc, such as energy shifts
      and splitting of nonlocal molecular orbitals. However, in CoPc-Co(II) where the
      Co atom is underneath a benzene lobe of CoPc, it only slightly modifies the
      electronic states of CoPc, and mainly local characteristics of specific molecular
      orbitals are affected, even though CoPc-Co(II) is more stable than CoPc-Co(I).
      Our DFT calculations give consistent results with the experiments, and related
      analyses based on the molecular orbital theory reveal mechanism behind the
      experimental observations.

PMID- 26203037
TI  - Latent heat induced rotation limited aggregation in 2D ice nanocrystals.
AB  - The basic science responsible for the fascinating shapes of ice crystals and
      snowflakes is still not understood. Insufficient knowledge of the interaction
      potentials and the lack of relevant experimental access to the growth process are
      to blame for this failure. Here, we study the growth of fractal nanostructures in
      a two-dimensional (2D) system, intercalated between mica and graphene. Based on
      our scanning tunneling spectroscopy data, we provide compelling evidence that
      these fractals are 2D ice. They grow while they are in material contact with the
      atmosphere at 20  degrees C and without significant thermal contact to the
      ambient. The growth is studied in situ, in real time and space at the nanoscale.
      We find that the growing 2D ice nanocrystals assume a fractal shape, which is
      conventionally attributed to Diffusion Limited Aggregation (DLA). However, DLA
      requires a low mass density mother phase, in contrast to the actual currently
      present high mass density mother phase. Latent heat effects and consequent
      transport of heat and molecules are found to be key ingredients for understanding
      the evolution of the snow (ice) flakes. We conclude that not the local
      availability of water molecules (DLA), but rather them having the locally
      required orientation is the key factor for incorporation into the 2D ice
      nanocrystal. In combination with the transport of latent heat, we attribute the
      evolution of fractal 2D ice nanocrystals to local temperature dependent rotation
      limited aggregation. The ice growth occurs under extreme supersaturation, i.e.,
      the conditions closely resemble the natural ones for the growth of complex 2D
      snow (ice) flakes and we consider our findings crucial for solving the
      "perennial" snow (ice) flake enigma. 

PMID- 26203038
TI  - Role of direct electron-phonon coupling across metal-semiconductor interfaces in
      thermal transport via molecular dynamics.
AB  - Motivated by significant interest in metal-semiconductor and metal-insulator
      interfaces and superlattices for energy conversion applications, we developed a
      molecular dynamics-based model that captures the thermal transport role of
      conduction electrons in metals and heat transport across these types of
      interface. Key features of our model, denoted eleDID (electronic version of
      dynamics with implicit degrees of freedom), are the natural description of
      interfaces and free surfaces and the ability to control the spatial extent of
      electron-phonon (e-ph) coupling. Non-local e-ph coupling enables the energy of
      conduction electrons to be transferred directly to the semiconductor/insulator
      phonons (as opposed to having to first couple to the phonons in the metal). We
      characterize the effect of the spatial e-ph coupling range on interface
      resistance by simulating heat transport through a metal-semiconductor interface
      to mimic the conditions of ultrafast laser heating experiments. Direct energy
      transfer from the conduction electrons to the semiconductor phonons not only
      decreases interfacial resistance but also increases the ballistic transport
      behavior in the semiconductor layer. These results provide new insight for
      experiments designed to characterize e-ph coupling and thermal transport at the
      metal-semiconductor/insulator interfaces. 

PMID- 26203039
TI  - On the electronic, structural, and thermodynamic properties of Au supported on
      alpha-Fe2O3 surfaces and their interaction with CO.
AB  - Extensive first principles calculations are carried out to investigate Au
      monomers and dimers supported on alpha-Fe2O3(0001) surfaces in terms of structure
      optimizations, electronic structure analyses, and ab initio thermodynamics
      calculations of surface phase diagrams. All computations rely on density
      functional theory in the generalized gradient approximation (Perdew-Burke
      Ernzerhof (PBE)) and account for on-site Coulomb interactions via inclusion of a
      Hubbard correction (PBE+U). The relative stability of Au monomers/dimers on the
      stoichiometric termination of alpha-Fe2O3(0001) decorated with various vacancies
      (multiple oxygen vacancies, iron vacancy, and mixed iron-oxygen vacancies) has
      been computed as a function of the oxygen chemical potential. The charge
      rearrangement induced by Au at the oxide contact is analyzed in detail and
      discussed. On one hand, ab initio thermodynamics predicts that under O-rich
      conditions, structures obtained by replacing a surface Fe atom with a Au atom are
      thermodynamically stable over a wide range of temperatures. On the other hand,
      the complex of a CO molecule on a Au atom substituting surface Fe atoms is
      thermodynamically stable only in a much more narrow range of values of the O
      chemical potential under O-rich conditions. In the case of a Au dimer, under O
      rich conditions, supported Au atoms at an O-Fe di-vacancy are more stable.
      However, upon CO adsorption, the complex of a CO molecule and 2 Au atoms located
      at a single Fe vacancy is more favorable. 

PMID- 26203040
TI  - Fingerprints of energy dissipation for exothermic surface chemical reactions: O2
      on Pd(100).
AB  - We present first-principles calculations of the sticking coefficient of O2 at
      Pd(100) to assess the effect of phononic energy dissipation on this kinetic
      parameter. For this, we augment dynamical simulations on six-dimensional
      potential energy surfaces (PESs) representing the molecular degrees of freedom
      with various effective accounts of surface mobility. In comparison to the
      prevalent frozen-surface approach, energy dissipation is found to qualitatively
      affect the calculated sticking curves. At the level of a generalized Langevin
      oscillator model, we achieve good agreement with experimental data. The agreement
      is similarly reached for PESs based on two different semi-local density
      functional theory functionals. This robustness of the simulated sticking curve
      does not extend to the underlying adsorption mechanism, which is predominantly
      directly dissociative for one functional or molecularly trapped for the other.
      Completely different adsorption mechanisms therewith lead to rather similar
      sticking curves that agree equally well with the experimental data. This
      highlights the danger of the prevalent practice to extract corresponding
      mechanistic details from simple fingerprints of measured sticking data for such
      exothermic surface reactions. 

PMID- 26203041
TI  - A computer simulation approach to quantify the true area and true area
      compressibility modulus of biological membranes.
AB  - We present a new computational approach to quantify the area per lipid and the
      area compressibility modulus of biological membranes. Our method relies on the
      analysis of the membrane fluctuations using our recently introduced coupled
      undulatory (CU) mode [Tarazona et al., J. Chem. Phys. 139, 094902 (2013)], which
      provides excellent estimates of the bending modulus of model membranes. Unlike
      the projected area, widely used in computer simulations of membranes, the CU area
      is thermodynamically consistent. This new area definition makes it possible to
      accurately estimate the area of the undulating bilayer, and the area per lipid,
      by excluding any contributions related to the phospholipid protrusions. We find
      that the area per phospholipid and the area compressibility modulus features a
      negligible dependence with system size, making possible their computation using
      truly small bilayers, involving a few hundred lipids. The area compressibility
      modulus obtained from the analysis of the CU area fluctuations is fully
      consistent with the Hooke's law route. Unlike existing methods, our approach
      relies on a single simulation, and no a priori knowledge of the bending modulus
      is required. We illustrate our method by analyzing 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine bilayers using the coarse grained MARTINI force-field.
      The area per lipid and area compressibility modulus obtained with our method and
      the MARTINI forcefield are consistent with previous studies of these bilayers. 

PMID- 26203042
TI  - Origin of melting point depression for rare gas solids confined in carbon pores.
AB  - To obtain insights into the mechanism of the melting-point depression of rare gas
      solids confined in crystalline carbon pores, we examined the freezing and melting
      behavior of Xe and Ar confined to the crystalline pores of ordered mesoporous
      carbons as well as compressed exfoliated graphite compared to the amorphous pores
      of ordered mesoporous silicas, by means of X-ray diffraction. For the Xe and Ar
      confined to the crystalline carbon pores, there was no appreciable thermal
      hysteresis between freezing and melting. Furthermore, the position of the main
      diffraction peak did not change appreciably on freezing and melting. This
      strongly suggests that the liquids confined in the carbon pores form a
      multilayered structure parallel to the smooth walls. For the Xe and Ar confined
      to the amorphous silica pores, on the other hand, the position of the main
      diffraction peak shifted into higher scattering angle on freezing suggested that
      the density of the confined solid is distinctly larger than for the confined
      liquid. Using compressed exfoliated graphite with carbon walls of higher
      crystallinity, we observed that three-dimensional (3D) microcrystals of Xe
      confined in the slit-shaped pores melted to leave the unmelted bilayers on the
      pore walls below the bulk triple point. The lattice spacing of the 3D
      microcrystals confined is larger by ~0.7% than that of the bilayer next to the
      pore walls in the vicinity of the melting point. 

PMID- 26203043
TI  - Rheology and morphology of no-slip sheared polymer nanocomposite under creep
      condition.
AB  - Dissipative particle dynamics simulations are performed on wet polymer
      nanocomposite blends under the discrete imposed velocity profile and no-slip
      boundary conditions. To be able to study the chain length dependency of the
      rheological properties, a number of blends of mono-disperse polymer chains of
      lengths varying from 10 to 100 repeat units and nanoparticles of diameters 2.5
      and 5 have been simulated. The wall velocity was imposed on a thin polymer layer
      (the no-slip layer). Linear velocity profiles for polymer confined in the pore
      were observed at the steady state. We found that the flow has a shear thinning
      effect on the chains with a radius of gyration less than the filler radius. Long
      chains (with a radius of gyration longer than the filler's radius), however, obey
      the Newtonian behavior over a much wider shear rate than that which causes shear
      thinning in short chains. The effect of particle-monomer interactions, polymer
      entanglements, chain morphology, and link formation on the shear rate dependency
      of the viscosity coefficient has been studied. Our results show that the particle
      polymer interactions have no effect on shear thinning behavior of the blend. In
      contrast, the long range polymer-polymer interactions and the chain length have
      considerable effects on the rheological behavior of the blend. Finally, the phase
      diagram of the rheological properties of polymer nanocomposite as a function of
      strain rate and the chain length is extracted. 

PMID- 26203044
TI  - An unconstrained DFT approach to microphase formation and application to binary
      Gaussian mixtures.
AB  - The formation of microphases in systems of particles interacting by repulsive,
      bounded potentials is studied by means of density-functional theory (DFT) using a
      simple, mean-field-like form for the free energy which has already been proven
      accurate for this class of soft interactions. In an effort not to constrain the
      configurations available to the system, we do not make any assumption on the
      functional form of the density profile rho(r), save for its being periodic. We
      sample rho(r) at a large number of points in the unit cell and minimize the free
      energy with respect to both the values assumed by rho(r) at these points and the
      lattice vectors which identify the Bravais lattice. After checking the accuracy
      of the method by applying it to a one-component generalized exponential model
      (GEM) fluid with pair potential epsilonexp[ - (r/R)(4)], for which extensive DFT
      and simulation results are already available, we turn to a binary mixture of
      Gaussian particles which some time ago was shown to support microphase formation
      [A. J. Archer, C. N. Likos, and R. Evans, J. Phys.: Condens. Matter 16, L297
      (2004)], but has not yet been investigated in detail. The phase diagram which we
      obtain, that supersedes the tentative one proposed by us in a former study [M.
      Carta, D. Pini, A. Parola, and L. Reatto, J. Phys.: Condens. Matter 24, 284106
      (2012)], displays cluster, tubular, and bicontinuous phases similar to those
      observed in block copolymers or oil/water/surfactant mixtures. Remarkably,
      bicontinuous phases occupy a rather large portion of the phase diagram. We also
      find two non-cubic phases, in both of which one species is preferentially located
      inside the channels left available by the other, forming helices of alternating
      chirality. The features of cluster formation in this mixture and in GEM
      potentials are also compared. 

PMID- 26203045
TI  - Note: How does the treatment of electrostatic interactions influence the
      magnitude of thermal polarization of water? The SPC/E model.

PMID- 26203046
TI  - Glitazones are associated with reduced risk of Parkinson's disease.

PMID- 26203047
TI  - Genome-wide transcriptome analysis reveals inactivation of Wnt/beta-catenin by
      3,3'-diindolylmethane inhibiting proliferation of colon cancer cells.
AB  - Multiple genetic and signaling pathway alterations underlie the development of
      colon cancer. We utilized genome-wide transcriptome analysis to identify
      important gene expression patterns following treatment with 3,3'-diindolylmethane
      (DIM), a natural compound derived from cruciferous vegetables, on colon cancer
      cells. Statistical analyses of gene expression data from DIM treated cells
      revealed that 692 genes were significantly upregulated, while 731 genes were down
      regulated. Putative gene networks showed that several oncogenes (beta-catenin,
      Myc and FOS) were significantly suppressed by DIM treatment. Using clinical data
      from colon cancer patients, activation of beta-catenin was found to be
      significantly associated with patient prognosis by Kaplan-Meir plot analysis. We
      validated the mRNA and protein expression levels of c-Myc, beta-catenin, and
      cyclin D1, all of which were significantly suppressed after DIM treatment in DLD
      1 and HCT116 cells. System level characterization of our findings suggests for
      the first time that beta-catenin and c-Myc, which are major genes involved in
      colon carcinogenesis, were significantly downregulated by DIM treatment in colon
      cancer cells. Therefore, targeting Wnt/beta-catenin signaling by DIM may be an
      attractive strategy for the prevention and treatment of colon cancer. 

PMID- 26203048
TI  - Ferric pyrophosphate: good things come to those who wait?

PMID- 26203051
TI  - Staff shortages and lack of data continue to blight England's NHS and care
      regulator.

PMID- 26203050
TI  - Neural mechanisms of social influence in adolescence.
AB  - During the transformative period of adolescence, social influence plays a
      prominent role in shaping young people's emerging social identities, and can
      impact their propensity to engage in prosocial or risky behaviors. In this study,
      we examine the neural correlates of social influence from both parents and peers,
      two important sources of influence. Nineteen adolescents (age 16-18 years)
      completed a social influence task during a functional magnetic resonance imaging
      (fMRI) scan. Social influence from both sources evoked activity in brain regions
      implicated in mentalizing (medial prefrontal cortex, left temporoparietal
      junction, right temporoparietal junction), reward (ventromedial prefrontal
      cortex), and self-control (right ventrolateral prefrontal cortex). These results
      suggest that mental state reasoning, social reward and self-control processes may
      help adolescents to evaluate others' perspectives and overcome the prepotent
      force of their own antecedent attitudes to shift their attitudes toward those of
      others. Findings suggest common neural networks involved in social influence from
      both parents and peers. 

PMID- 26203052
TI  - Mark Newbold: Resilient, thoughtful, genuine.

PMID- 26203049
TI  - Increased cathepsin D protein expression is a biomarker for osteosarcomas,
      pulmonary metastases and other bone malignancies.
AB  - Cancer proteomics provide a powerful approach to identify biomarkers for
      personalized medicine. Particularly, biomarkers for early detection, prognosis
      and therapeutic intervention of bone cancers, especially osteosarcomas, are
      missing. Initially, we compared two-dimensional gel electrophoresis (2-DE)-based
      protein expression pattern between cell lines of fetal osteoblasts, osteosarcoma
      and pulmonary metastasis derived from osteosarcoma. Two independent statistical
      analyses by means of PDQuest(r) and SameSpot(r) software revealed a common set of
      34 differentially expressed protein spots (p < 0.05). 17 Proteins were identified
      by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in one
      high-ranked network associated with Gene Expression, Cell Death and Cell-To-Cell
      Signaling and Interaction. Ran/TC4-binding protein (RANBP1) and Cathepsin D
      (CTSD) were further validated by Western Blot in cell lines while the latter one
      showed higher expression differences also in cytospins and in clinical samples
      using tissue microarrays comprising osteosarcomas, metastases, other bone
      malignancies, and control tissues. The results show that protein expression
      patterns distinguish fetal osteoblasts from osteosarcomas, pulmonary metastases,
      and other bone diseases with relevant sensitivities between 55.56% and 100% at
      >=87.50% specificity. Particularly, CTSD was validated in clinical material and
      could thus serve as a new biomarker for bone malignancies and potentially guide
      individualized treatment regimes.

PMID- 26203053
TI  - Correlation between cytotoxicity induced by Pseudomonas aeruginosa clinical
      isolates from acute infections and IL-1beta secretion in a model of human THP-1
      monocytes.
AB  - Type III secretion system (T3SS) in Pseudomonas aeruginosa is associated with
      poor clinical outcome in acute infections. T3SS allows for injection of bacterial
      exotoxins (e.g. ExoU or ExoS) into the host cell, causing cytotoxicity. It also
      activates the cytosolic NLRC4 inflammasome, activating caspase-1, inducing
      cytotoxicity and release of mature IL-1beta, which impairs bacterial clearance.
      In addition, flagellum-mediated motility has been suggested to also modulate
      inflammasome response and IL-1beta release. Yet the capacity of clinical isolates
      to induce IL-1beta release and its relation with cytotoxicity have never been
      investigated. Using 20 clinical isolates from acute infections with variable T3SS
      expression levels and human monocytes, our aim was to correlate IL-1beta release
      with toxin expression, flagellar motility and cytotoxicity. ExoU-producing
      isolates caused massive cell death but minimal release of IL-1beta, while those
      expressing T3SS but not ExoU (i.e. expressing ExoS or no toxins) induced caspase
      1 activation and IL-1beta release, the level of which was correlated with
      cytotoxicity. Both effects were prevented by a specific caspase-1 inhibitor.
      Flagellar motility was not correlated with cytotoxicity or IL-1beta release. No
      apoptosis was detected. Thus, T3SS cytotoxicity is accompanied by a modification
      in cytokine balance for P. aeruginosa clinical isolates that do not express ExoU.

PMID- 26203054
TI  - Biomek Cell Workstation: A Flexible System for Automated 3D Cell Cultivation.
AB  - The shift from 2D cultures to 3D cultures enables improvement in cell culture
      research due to better mimicking of in vivo cell behavior and environmental
      conditions. Different cell lines and applications require altered 3D constructs.
      The automation of the manufacturing and screening processes can advance the
      charge stability, quality, repeatability, and precision. In this study we
      integrated the automated production of three 3D cell constructs (alginate beads,
      spheroid cultures, pellet cultures) using the Biomek Cell Workstation and
      compared them with the traditional manual methods and their consequent
      bioscreening processes (proliferation, toxicity; days 14 and 35) using a high
      throughput screening system. Moreover, the possible influence of antibiotics
      (penicillin/streptomycin) on the production and screening processes was
      investigated. The cytotoxicity of automatically produced 3D cell cultures (with
      and without antibiotics) was mainly decreased. The proliferation showed mainly
      similar or increased results for the automatically produced 3D constructs. We
      concluded that the traditional manual methods can be replaced by the automated
      processes. Furthermore, the formation, cultivation, and screenings can be
      performed without antibiotics to prevent possible effects. 

PMID- 26203055
TI  - A Highly Flexible, Automated System Providing Reliable Sample Preparation in
      Element- and Structure-Specific Measurements.
AB  - Life science areas require specific sample pretreatment to increase the
      concentration of the analytes and/or to convert the analytes into an appropriate
      form for the detection and separation systems. Various workstations are
      commercially available, allowing for automated biological sample pretreatment.
      Nevertheless, due to the required temperature, pressure, and volume conditions in
      typical element and structure-specific measurements, automated platforms are not
      suitable for analytical processes. Thus, the purpose of the presented
      investigation was the design, realization, and evaluation of an automated system
      ensuring high-precision sample preparation for a variety of analytical
      measurements. The developed system has to enable system adaption and high
      performance flexibility. Furthermore, the system has to be capable of dealing
      with the wide range of required vessels simultaneously, allowing for less cost
      and time-consuming process steps. However, the system's functionality has been
      confirmed in various validation sequences. Using element-specific measurements,
      the automated system was up to 25% more precise compared to the manual procedure
      and as precise as the manual procedure using structure-specific measurements. 

PMID- 26203056
TI  - Acoustic Sample Deposition MALDI-MS (ASD-MALDI-MS): A Novel Process Flow for
      Quality Control Screening of Compound Libraries.
AB  - In the early stages of drug discovery, high-throughput screening (HTS) of
      compound libraries against pharmaceutical targets is a common method to identify
      potential lead molecules. For these HTS campaigns to be efficient and successful,
      continuous quality control of the compound collection is necessary and crucial.
      However, the large number of compound samples and the limited sample amount pose
      unique challenges. Presented here is a proof-of-concept study for a novel process
      flow for the quality control screening of small-molecule compound libraries that
      consumes only minimal amounts of samples and affords compound-specific molecular
      data. This process employs an acoustic sample deposition (ASD) technique for the
      offline sample preparation by depositing nanoliter volumes in an array format
      onto microscope glass slides followed by matrix-assisted laser
      desorption/ionization mass spectrometric (MALDI-MS) analysis. An initial study of
      a 384-compound array employing the ASD-MALDI-MS workflow resulted in a 75% first
      pass positive identification rate with an analysis time of <1 s per sample. 

PMID- 26203057
TI  - Ebola Virus: Sensationalism, Science, and Human Rights.
AB  - Outbreaks of the filoviruses, Ebola and Marburg, usually garner immense public
      attention, often with a sensationalist bent in the lay press, focused on the
      apparently mysterious origins of the outbreak and the high mortality rates. The
      scientific community may present a more objective viewpoint, but usually with a
      rather technical focus on identifying epidemiological risk factors and
      experimental therapies and vaccines. Often lost in the discussion are the human
      rights elements that consistently underlie large outbreaks of these dangerous
      viruses. 

PMID- 26203058
TI  - Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T
      Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways.
AB  - Middle East respiratory syndrome (MERS) is associated with a mortality rate of
      >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human
      macrophages and dendritic cells and induce cytokine dysregulation. Here, we
      further investigated the interplay between human primary T cells and MERS-CoV in
      disease pathogenesis. Importantly, our results suggested that MERS-CoV
      efficiently infected T cells from the peripheral blood and from human lymphoid
      organs, including the spleen and the tonsil. We further demonstrated that MERS
      CoV infection induced apoptosis in T cells, which involved the activation of both
      the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of
      spleen sections from MERS-CoV-infected common marmosets demonstrated the presence
      of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested
      that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis
      might partly contribute to the high pathogenicity of the virus. 

PMID- 26203059
TI  - Discovery of T-Cell Infection and Apoptosis by Middle East Respiratory Syndrome
      Coronavirus.

PMID- 26203060
TI  - Trends in health care expenditure in U.S. adults with diabetes: 2002-2011.
AB  - OBJECTIVE: Direct medical cost of diabetes in the U.S. has been estimated to be
      2.3 times higher relative to individuals without diabetes. This study examines
      trends in health care expenditures by expenditure category in U.S. adults with
      diabetes between 2002 and 2011. RESEARCH DESIGN AND METHODS: We analyzed 10 years
      of data representing a weighted population of 189,013,514 U.S. adults aged >=18
      years from the Medical Expenditure Panel Survey. We used a novel two-part model
      to estimate adjusted mean and incremental medical expenditures by diabetes
      status, while adjusting for demographics, comorbidities, and time. RESULTS:
      Relative to individuals without diabetes ($5,058 [95% CI 4,949-5,166]),
      individuals with diabetes ($12,180 [11,775-12,586]) had more than double the
      unadjusted mean direct expenditures over the 10-year period. After adjustment for
      confounders, individuals with diabetes had $2,558 (2,266-2,849) significantly
      higher direct incremental expenditures compared with those without diabetes. For
      individuals with diabetes, inpatient expenditures rose initially from $4,014 in
      2002/2003 to $4,183 in 2004/2005 and then decreased continuously to $3,443 in
      2010/2011, while rising steadily for individuals without diabetes. The estimated
      unadjusted total direct expenditures for individuals with diabetes were $218.6
      billion/year and adjusted total incremental expenditures were approximately $46
      billion/year. CONCLUSIONS: Our findings show that compared with individuals
      without diabetes, individuals with diabetes had significantly higher health
      expenditures from 2002 to 2011 and the bulk of the expenditures came from
      hospital inpatient and prescription expenditures.

PMID- 26203061
TI  - Testing for rewards: a pilot study to improve type 1 diabetes management in
      adolescents.
AB  - OBJECTIVE: To evaluate the effectiveness of monetary reinforcement to increase
      the frequency of self-monitoring blood glucose (SMBG). RESEARCH DESIGN AND
      METHODS: Ten adolescents with poorly controlled diabetes enrolled in a 12-week
      program in which they earned monetary reinforcers based on SMBG frequency ($0.10
      per test, with bonuses for >=4 tests per day, and $251.40 maximum). RESULTS: SMBG
      increased from 1.8 +/- 1.0 to 4.9 +/- 1.0 tests per day (P < 0.001) with 90%
      completing four or more tests per day. Mean A1C fell from 9.3 +/- 0.9% to 8.4 +/-
      1.5% (P = 0.05). Adolescents and parents reported high satisfaction with
      procedures. CONCLUSIONS: Reinforcing adolescents for SMBG may increase testing
      and improve A1C.

PMID- 26203063
TI  - Diabetes, lower-extremity amputation, and death.
AB  - OBJECTIVE: The goal of the study was to determine whether complications of
      diabetes well-known to be associated with death such as cardiovascular disease
      and renal failure fully explain the higher rate of death in those who have
      undergone a lower-extremity amputation (LEA). RESEARCH DESIGN AND METHODS: This
      was a longitudinal cohort study of patients cared for in the Health Improvement
      Network. Our primary exposure was LEA and outcome was all-cause death. Our "risk
      factor variables" included a history of cardiovascular disease (a history of
      myocardial infarctions, cerebrovascular accident, and peripheral vascular
      disease/arterial insufficiency), Charlson index, and a history of chronic kidney
      disease. We estimated the effect of LEA on death using Cox proportional hazards
      models. RESULTS: The hazard ratio (HR) for death after an LEA was 3.02 (95% CI
      2.90, 3.14). The fully adjusted (all risk factor variables) LEA HR was diminished
      only by ~22% to 2.37 (2.27, 2.48). Furthermore, LEA had an area under the
      receiver operating curve (AUC) of 0.51, which is poorly predictive, and the fully
      adjusted model had an AUC of 0.77, which is better but not strongly predictive.
      Sensitivity analysis revealed that it is unlikely that there exists an unmeasured
      confounder that can fully explain the association of LEA with death. CONCLUSIONS:
      Individuals with diabetes and an LEA are more likely to die at any given point in
      time than those who have diabetes but no LEA. While some of this variation can be
      explained by known complications of diabetes, there remains a large amount of
      unexplained variation.

PMID- 26203062
TI  - Relationship of urologic complications with health-related quality of life and
      perceived value of health in men and women with type 1 diabetes: the Diabetes
      Control and Complications Trial/Epidemiology of Interventions and Complications
      (DCCT/EDIC) cohort.
AB  - OBJECTIVE: Limited information exists about the influence of urologic
      complications on health-related quality of life (HRQOL) in patients with type 1
      diabetes. RESEARCH DESIGN AND METHODS: We studied 664 men and 580 women from the
      Diabetes Control and Complications Trial/Epidemiology of Interventions and
      Complications Study: mean ages were 51.6 +/- 6.6 and 50.6 +/- 7.2 years and
      duration of diabetes was 29.5 +/- 4.8 and 29.8 +/- 5.1 years, respectively. We
      assessed associations of sexual dysfunction, lower urinary tract symptoms (LUTS),
      and, in women, urinary incontinence (UI) with general quality of life (SF-36),
      perceived value of health (EuroQol-5), diabetes-related quality of life (Diabetes
      Quality of Life Scale [DQOL]), and psychiatric symptoms (Symptom Checklist 90-R).
      RESULTS: In both men and women, urologic complications adversely affected HRQOL
      and psychiatric symptoms, even after accounting for history of depression leading
      to treatment. Multivariable analyses accounting for the presence of diabetic
      retinopathy, neuropathy, and nephropathy also revealed substantial independent
      effects. In men, for example, the odds (95% CI) of a low DQOL score (<=25th
      percentile) were 3.01 (1.90-4.75) times greater with erectile dysfunction and
      2.65 (1.68-4.18) times greater with LUTS and in women, 2.04 (1.25-3.35) times
      greater with sexual dysfunction and 2.71 (1.72-4.27) times greater with UI/LUTS
      combined compared with men and women without such complications. Similar effects
      were observed for the other measures. CONCLUSIONS: Sexual dysfunction and urinary
      complications with type 1 diabetes are associated with decreased quality of life
      and perceived value of health and with higher levels of psychiatric symptoms,
      even after accounting for other diabetes complications and depression treatment.

PMID- 26203064
TI  - Diabetic Ketoacidosis and Related Events in the Canagliflozin Type 2 Diabetes
      Clinical Program.
AB  - OBJECTIVE: This study assessed the incidence of serious adverse events of
      diabetic ketoacidosis (DKA) among patients with type 2 diabetes treated with
      canagliflozin. RESEARCH DESIGN AND METHODS: All serious adverse events of DKA and
      related events (ketoacidosis, metabolic acidosis, and acidosis) from 17,596
      patients from randomized studies of canagliflozin through 11 May 2015 were
      analyzed. RESULTS: Serious adverse events of DKA and related events were reported
      in 12 patients (0.07%), including 4 (0.07%), 6 (0.11%), and 2 (0.03%) treated
      with canagliflozin 100 and 300 mg and comparator, respectively; corresponding
      incidence rates were 0.522, 0.763, and 0.238 per 1,000 patient-years,
      respectively. Most patients with DKA and related events had a blood glucose >300
      mg/dL (16.7 mmol/L) at presentation of DKA, were on insulin, and had DKA
      precipitating factors, including some with type 1 diabetes/latent autoimmune
      diabetes of adulthood. CONCLUSIONS: DKA and related events occurred at a low
      frequency in the canagliflozin type 2 diabetes program, with an incidence
      consistent with limited existing observational data in the general population
      with type 2 diabetes.

PMID- 26203065
TI  - Screening for cognitive deficits in 8 to 14-year old children with cerebellar
      tumors using self-report measures of executive and behavioral functioning and
      health-related quality of life.
AB  - BACKGROUND: We aimed to identify a brief screening measure for detection of
      cognitive deficit in children treated for cerebellar tumors that would be useful
      in clinical practice. METHODS: A sample of 72 children, aged 8-14 years, and
      within 3 years post diagnosis for standard-risk medulloblastoma (n = 37) or low
      grade cerebellar astrocytoma (n = 35) and 38 children in a nontumor group were
      assessed using teacher-, parent-, and child-report of the Behavior Rating
      Inventory of Executive Function (BRIEF), Strengths and Difficulties Questionnaire
      (SDQ), and Pediatric Quality of Life Inventory (PedsQL). The accuracy of these
      scores as a screen for a full-scale Intelligence Quotient (FSIQ) < 80 on the
      Wechsler Intelligence Scale for Children (WISC-IV UK) was assessed using their
      receiver operating characteristic (ROC) curves. RESULTS: The questionnaires with
      the highest areas under the ROC curves were the child- and parent-report PedsQL,
      the teacher-report BRIEF, and the SDQ. At optimal cutoff scores, their
      sensitivities (95% CIs) to cases of FSIQ < 80 were 84 (60-96)%, 65 (41-84)%, 79
      (54-93)%, and 84 (60-96)%, and their specificities (95% CIs) were 79 (68-86)%, 87
      (77-93)%, 77 (66-86)%, and 71 (64-84)% respectively. All cases of FSIQ < 80
      screened positive on either teacher-report SDQ or self-report PedsQL.
      CONCLUSIONS: The PedsQL child- and parent-report and the teacher-report BRIEF and
      SDQ have moderately good accuracy for discriminating between children with and
      without a FSIQ < 80. The PedsQL could be used in a clinical setting, and the
      BRIEF and SDQ in an educational setting, to screen for cases with FSIQ < 80 in
      children treated for brain tumors.

PMID- 26203066
TI  - Multicenter imaging outcomes study of The Cancer Genome Atlas glioblastoma
      patient cohort: imaging predictors of overall and progression-free survival.
AB  - BACKGROUND: Despite an aggressive therapeutic approach, the prognosis for most
      patients with glioblastoma (GBM) remains poor. The aim of this study was to
      determine the significance of preoperative MRI variables, both quantitative and
      qualitative, with regard to overall and progression-free survival in GBM.
      METHODS: We retrospectively identified 94 untreated GBM patients from the Cancer
      Imaging Archive who had pretreatment MRI and corresponding patient outcomes and
      clinical information in The Cancer Genome Atlas. Qualitative imaging assessments
      were based on the Visually Accessible Rembrandt Images feature-set criteria.
      Volumetric parameters were obtained of the specific tumor components: contrast
      enhancement, necrosis, and edema/invasion. Cox regression was used to assess
      prognostic and survival significance of each image. RESULTS: Univariable Cox
      regression analysis demonstrated 10 imaging features and 2 clinical variables to
      be significantly associated with overall survival. Multivariable Cox regression
      analysis showed that tumor-enhancing volume (P = .03) and eloquent brain
      involvement (P < .001) were independent prognostic indicators of overall
      survival. In the multivariable Cox analysis of the volumetric features, the
      edema/invasion volume of more than 85 000 mm(3) and the proportion of enhancing
      tumor were significantly correlated with higher mortality (Ps = .004 and .003,
      respectively). CONCLUSIONS: Preoperative MRI parameters have a significant
      prognostic role in predicting survival in patients with GBM, thus making them
      useful for patient stratification and endpoint biomarkers in clinical trials.

PMID- 26203068
TI  - Institutional blind spot around mental health needs of paediatric patients.

PMID- 26203069
TI  - Lipid Peroxide-Mediated Oxidative Rearrangement of the Pyrazinone Carboxamide
      Core of Neutrophil Elastase Inhibitor AZD9819 in Blood Plasma Samples.
AB  - This study focused on the mechanistic interpretation of ex vivo oxidation of a
      candidate drug in blood plasma samples. An unexpected lipid peroxide-mediated
      epoxidation followed by a dramatic rearrangement led to production of a five
      membered oxazole derivative from the original six-membered pyrazinone-carboxamide
      core of a human neutrophil elastase inhibitor, 6-(1-(4-cyanophenyl)-1H-pyrazol-5
      yl)-N-ethyl-5-methyl-3-oxo-4-(3-(trifluoromethyl)phenyl)-3,4-dihydropyrazine-2
      carboxamide (AZD9819). The rearranged oxidation product 2-(1-(4-cyanophenyl)-1H
      pyrazol-5-yl)-5-(N-ethylacetamido)-N-(3-(trifluoromethyl)phenyl)oxazole-4
      carboxamide was characterized by accurate-mass tandem mass spectrometry
      fragmentations, by two-dimensional NMR and X-ray crystallography of an authentic
      standard, and by incorporation of an (18)O atom from molecular (18)O2 to the
      location predicted by our proposed mechanism. The lipid peroxide-mediated
      oxidation was demonstrated by using human low-density lipoprotein (LDL) in pH 7.4
      phosphate buffer and by inhibiting the oxidation with ascorbic acid or l
      glutathione, two antioxidants effective in both plasma and the LDL incubation. A
      nucleophilic mechanism for the epoxidation of AZD9819 by lipid hydroperoxides
      explains the prevention of its ex vivo oxidation by acidification of the plasma
      samples. The discovery of the lipid peroxide-dependent oxidation of an analyte
      and the means of prevention could provide valuable information for
      biotransformation and bioanalysis.

PMID- 26203067
TI  - Intratumoral heterogeneity in glioblastoma: don't forget the peritumoral brain
      zone.
AB  - Glioblastoma (GB) is the most frequent and aggressive primary tumor of the
      central nervous system. Prognosis remains poor despite ongoing progress. In cases
      where the gadolinium-enhanced portion of the GB is completely resected, 90% of
      recurrences occur at the margin of surgical resection in the macroscopically
      normal peritumoral brain zone (PBZ). Intratumoral heterogeneity in GB is
      currently a hot topic in neuro-oncology, and the GB PBZ may be involved in this
      phenomenon. Indeed, this region, which possesses specific properties, has been
      less studied than the core of the GB tumor. The high rate of local recurrence in
      the PBZ and the limited success of targeted therapies against GB demonstrate the
      need for a better understanding of the PBZ. We present here a review of the
      literature on the GB PBZ, focusing on its radiological, cellular, and molecular
      characteristics. We discuss how intraoperative analysis of the PBZ is important
      for the optimization of surgical resection and the development of targeted
      therapies against GB. 

PMID- 26203070
TI  - Many US parents have poor understanding of proper antibiotic use, study finds.

PMID- 26203071
TI  - Biotinidase deficiency mimicking neuromyelitis optica: Initially exhibiting
      symptoms in adulthood.
AB  - BACKGROUND: Children with untreated biotinidase deficiency can experience
      variable symptoms depending on their age of presentation. Older children and
      adolescents can exhibit predominant neurological deficits including para- or
      tetraparesis and vision loss. METHODS: We report the first case of delayed-onset
      biotinidase deficiency in a young adult. RESULTS: A 22-year-old man presented
      with a disabling extensive myelopathy and bilateral optic neuropathy which
      mimicked the findings of a (seronegative) neuromyelitis optica. Imaging
      investigations were characterized by an MRI T2 hyper-intensity involving the
      spinal cord, the optic nerves, the fornix and the mammillar bodies, together with
      an increased (18)F-FDG uptake on positron emission tomography. He was ultimately
      shown to have profound biotinidase deficiency due to a novel missense mutation
      and was partly improved by oral biotin therapy. CONCLUSION: This individual
      exemplifies the need to include biotinidase deficiency in the differential
      diagnosis of patients with extensive myelopathy and/or bilateral optic neuropathy
      and argues for newborn screening for the disorder.

PMID- 26203072
TI  - Contribution of the cerebellum to cognitive performance in children and
      adolescents with multiple sclerosis.
AB  - BACKGROUND: Posterior fossa lesions are common in pediatric-onset multiple
      sclerosis (MS), which is of concern, given the known role of the cerebellum in
      cognition. OBJECTIVES: To investigate the relationship between cerebellar
      pathology and cognitive function in youth with pediatric-onset MS. METHODS:
      Twenty-eight pediatric-onset relapsing-remitting MS patients (21 girls; mean age
      16.2 years; mean disease duration 4.3 years, median Expanded Disability Status
      Scale 1.25) were compared to 33 age- and sex-matched healthy controls.
      Participants underwent structural magnetic resonance imaging (MRI) and
      neuropsychological evaluation to assess intelligence, attention, processing
      speed, language, visuo-motor integration, and fine-motor dexterity. Associations
      between cognitive outcomes and cerebellar volume independent of cerebral volume
      were examined. RESULTS: Cognitive and motor performance of the MS group was
      reduced relative to controls (all p<0.003). While cerebellar volumes did not
      differ between groups, cerebellar posterior lobe volume and infratentorial lesion
      volume accounted for extra variance on measures of information processing
      (R(2)=0.43; p=0.02) and vocabulary (R(2)=0.56; p=0.04) in patients (controlling
      for cerebral volume and sex), but not in controls. CONCLUSION: Smaller cerebellar
      posterior lobe volume, a known region for cognitive processing, and increased
      lesion burden in the posterior fossa adversely impact cognitive function, an
      important functional consequence of MS onset during childhood.

PMID- 26203073
TI  - Enteral Nutrition for Adults in the Hospital Setting.
AB  - In patients unable to tolerate oral intake, multiple options of nutrient delivery
      are available to the clinician. Administration of enteral nutrition (EN) has long
      been considered the standard of care for nutrition support among patients unable
      to meet energy and protein requirements orally. Healthcare practitioners must
      make careful decisions related to ordering, administering, and monitoring EN
      therapy. In the hospital setting, the registered dietitian is a key resource in
      enteral formula selection and method of administration, monitoring for and
      troubleshooting EN-related complications, and transitioning to oral feeding. The
      hospital setting also presents many unique challenges in providing optimal
      nutrition to the enterally fed patient. 

PMID- 26203074
TI  - Recommendations for Manganese Supplementation to Adult Patients Receiving Long
      Term Home Parenteral Nutrition: An Analysis of the Supporting Evidence.
AB  - INTRODUCTION: Manganese (Mn) toxicity is often observed in adult patients
      receiving long-term home parenteral nutrition (HPN), and differing
      recommendations on the safe level of Mn administration to these patients have
      been made in the literature over the past 10 years. METHODS: This systematic
      review used the National Health and Medical Research Council (NHMRC) evidence
      hierarchy to assess the design and strength of individual studies (high I to low
      IV) and the overall grade of evidence (grade A high to grade D low). RESULTS:
      Eight studies met the inclusion criteria. Levels of evidence ranged from high
      (NHMRC II) to mid-level (III-3). A widespread recommendation in the literature
      for patients receiving long-term HPN is 55 ug (1 umol) Mn/d. CONCLUSION: The
      recommendation of 55 ug (1 umol) Mn/d is of moderate-strength evidence (NHMRC B
      grade). There is limited evidence to support not supplementing Mn to patients
      receiving long-term HPN. Further intervention studies providing high-level
      evidence (II and above) are required to determine the safety of not supplementing
      Mn to all patients receiving long-term HPN.

PMID- 26203077
TI  - App-enabled trial participation: Tectonic shift or tepid rumble?

PMID- 26203075
TI  - Defective triglyceride biosynthesis in CETP-deficient SW872 cells.
AB  - We previously reported that reducing the expression of cholesteryl ester transfer
      protein (CETP) disrupts cholesterol homeostasis in SW872 cells and causes an ~50%
      reduction in TG. The causes of this reduced TG content, investigated here, could
      not be attributed to changes in the differentiation status of CETP-deficient
      cells, nor was there evidence of endoplasmic reticulum (ER) stress. In short-term
      studies, the total flux of oleate through the TG biosynthetic pathway was not
      altered in CETP-deficient cells, although mRNA levels of some pathway enzymes
      were different. However, the conversion of diglyceride (DG) to TG was impaired.
      In longer-term studies, newly synthesized TG was not effectively transported to
      lipid droplets, yet this lipid did not accumulate in the ER, apparently due to
      elevated lipase activity in this organelle. DG, shown to be a novel CETP
      substrate, was also inefficiently transferred to lipid droplets. This may reduce
      TG synthesis on droplets by resident diacylglycerol acyltransferase. Overall,
      these data suggest that the decreased TG content of CETP-deficient cells arises
      from the reduced conversion of DG to TG in the ER and/or on the lipid droplet
      surface, and enhanced TG degradation in the ER due to its ineffective transport
      from this organelle. 

PMID- 26203076
TI  - ABCA1 contributes to macrophage deposition of extracellular cholesterol.
AB  - We previously reported that cholesterol-enriched macrophages excrete cholesterol
      into the extracellular matrix. A monoclonal antibody that detects cholesterol
      microdomains labels the deposited extracellular particles. Macro-phage deposition
      of extracellular cholesterol depends, in part, on ABCG1, and this cholesterol can
      be mobilized by HDL components of the reverse cholesterol transport process. The
      objective of the current study was to determine whether ABCA1 also contributes to
      macrophage deposition of extracellular cholesterol. ABCA1 functioned in
      extracellular cholesterol deposition. The liver X receptor agonist, TO901317
      (TO9), an ABCA1-inducing factor, restored cholesterol deposition that was absent
      in cholesterol-enriched ABCG1(-/-) mouse macrophages. In addition, the ABCA1
      inhibitor, probucol, blocked the increment in cholesterol deposited by TO9
      treated wild-type macrophages, and completely inhibited deposition from TO9
      treated ABCG1(-/-) macrophages. Lastly, ABCA1(-/-) macrophages deposited much
      less extracellular cholesterol than wild-type macrophages. These findings
      demonstrate a novel function of ABCA1 in contributing to macrophage export of
      cholesterol into the extracellular matrix. 

PMID- 26203078
TI  - Optimizing sharing of hospital biobank samples.
AB  - Implementing technical guidelines and standards as well as ways to boost
      cooperation should facilitate sharing of hospital biobank samples. 

PMID- 26203079
TI  - Comment on "Tracking donor-reactive T cells: Evidence for clonal deletion in
      tolerant kidney transplant patients".

PMID- 26203080
TI  - Author response to comment on "Tracking donor-reactive T cells: Evidence for
      clonal deletion in tolerant kidney transplant patients".

PMID- 26203081
TI  - The prodrug DHED selectively delivers 17beta-estradiol to the brain for treating
      estrogen-responsive disorders.
AB  - Many neurological and psychiatric maladies originate from the deprivation of the
      human brain from estrogens. However, current hormone therapies cannot be used
      safely to treat these conditions commonly associated with menopause because of
      detrimental side effects in the periphery. The latter also prevents the use of
      the hormone for neuroprotection. We show that a small-molecule bioprecursor
      prodrug, 10beta,17beta-dihydroxyestra-1,4-dien-3-one (DHED), converts to 17beta
      estradiol in the brain after systemic administration but remains inert in the
      rest of the body. The localized and rapid formation of estrogen from the prodrug
      was revealed by a series of in vivo bioanalytical assays and through in vivo
      imaging in rodents. DHED treatment efficiently alleviated symptoms that
      originated from brain estrogen deficiency in animal models of surgical menopause
      and provided neuroprotection in a rat stroke model. Concomitantly, we determined
      that 17beta-estradiol formed in the brain from DHED elicited changes in gene
      expression and neuronal morphology identical to those obtained after direct
      17beta-estradiol treatment. Together, complementary functional and mechanistic
      data show that our approach is highly relevant therapeutically, because
      administration of the prodrug selectively produces estrogen in the brain
      independently from the route of administration and treatment regimen. Therefore,
      peripheral responses associated with the use of systemic estrogens, such as
      stimulation of the uterus and estrogen-responsive tumor growth, were absent.
      Collectively, our brain-selective prodrug approach may safely provide estrogen
      neuroprotection and medicate neurological and psychiatric symptoms developing
      from estrogen deficiency, particularly those encountered after surgical
      menopause, without the adverse side effects of current hormone therapies. 

PMID- 26203082
TI  - Fitness cost of antibiotic susceptibility during bacterial infection.
AB  - Advances in high-throughput DNA sequencing allow for a comprehensive analysis of
      bacterial genes that contribute to virulence in a specific infectious setting.
      Such information can yield new insights that affect decisions on how to best
      manage major public health issues such as the threat posed by increasing
      antimicrobial drug resistance. Much of the focus has been on the consequences of
      the selective advantage conferred on drug-resistant strains during antibiotic
      therapy. It is thought that the genetic and phenotypic changes that confer
      resistance also result in concomitant reductions in in vivo fitness, virulence,
      and transmission. However, experimental validation of this accepted paradigm is
      modest. Using a saturated transposon library of Pseudomonas aeruginosa, we
      identified genes across many functional categories and operons that contributed
      to maximal in vivo fitness during lung infections in animal models. Genes that
      bestowed both intrinsic and acquired antibiotic resistance provided a positive in
      vivo fitness advantage to P. aeruginosa during infection. We confirmed these
      findings in the pathogenic bacteria Acinetobacter baumannii and Vibrio cholerae
      using murine and rabbit infection models, respectively. Our results show that
      efforts to confront the worldwide increase in antibiotic resistance might be
      exacerbated by fitness advantages that enhance virulence in drug-resistant
      microbes. 

PMID- 26203083
TI  - Human NK cell repertoire diversity reflects immune experience and correlates with
      viral susceptibility.
AB  - Innate natural killer (NK) cells are diverse at the single-cell level because of
      variegated expressions of activating and inhibitory receptors, yet the
      developmental roots and functional consequences of this diversity remain unknown.
      Because NK cells are critical for antiviral and antitumor responses, a better
      understanding of their diversity could lead to an improved ability to harness
      them therapeutically. We found that NK diversity is lower at birth than in
      adults. During an antiviral response to either HIV-1 or West Nile virus, NK
      diversity increases, resulting in terminal differentiation and cytokine
      production at the cost of cell division and degranulation. In African women
      matched for HIV-1 exposure risk, high NK diversity is associated with increased
      risk of HIV-1 acquisition. Existing diversity may therefore decrease the
      flexibility of the antiviral response. Collectively, the data reveal that human
      NK diversity is a previously undefined metric of immune history and function that
      may be clinically useful in forecasting the outcomes of infection and malignancy.

PMID- 26203084
TI  - Inhibition of the alternative complement pathway preserves photoreceptors after
      retinal injury.
AB  - Degeneration of photoreceptors is a primary cause of vision loss worldwide,
      making the underlying mechanisms surrounding photoreceptor cell death critical to
      developing new treatment strategies. Retinal detachment, characterized by the
      separation of photoreceptors from the underlying retinal pigment epithelium, is a
      sight-threatening event that can happen in a number of retinal diseases. The
      detached photoreceptors undergo apoptosis and programmed necrosis. Given that
      photoreceptors are nondividing cells, their loss leads to irreversible visual
      impairment even after successful retinal reattachment surgery. To better
      understand the underlying disease mechanisms, we analyzed innate immune system
      regulators in the vitreous of human patients with retinal detachment and
      correlated the results with findings in a mouse model of retinal detachment. We
      identified the alternative complement pathway as promoting early photoreceptor
      cell death during retinal detachment. Photoreceptors down-regulate membrane-bound
      inhibitors of complement, allowing for selective targeting by the alternative
      complement pathway. When photoreceptors in the detached retina were removed from
      the primary source of oxygen and nutrients (choroidal vascular bed), the retina
      became hypoxic, leading to an up-regulation of complement factor B, a key
      mediator of the alternative pathway. Inhibition of the alternative complement
      pathway in knockout mice or through pharmacological means ameliorated
      photoreceptor cell death during retinal detachment. Our current study begins to
      outline the mechanism by which the alternative complement pathway facilitates
      photoreceptor cell death in the damaged retina. 

PMID- 26203085
TI  - Disease-Specific Survival with Spindle Cell Carcinoma of the Head and Neck.
AB  - OBJECTIVES: (1) Determine factors influencing survival in patients diagnosed with
      spindle cell carcinoma (SpCC), a rare variant of head and neck squamous cell
      carcinoma (SCC). (2) Compare survival of patients with SpCC to those with
      conventional SCC. STUDY DESIGN: Retrospective cohort study. SETTING:
      Surveillance, Epidemiology, and End Results 18 database (years 2004-2009).
      SUBJECTS AND METHODS: Among patients receiving treatment for a single primary in
      the oral cavity, oropharynx, hypopharynx, or larynx, 118 subjects with SpCC and
      18,298 subjects with SCC were identified with complete data for the variables of
      age, sex, grade, tumor size, stage group, and TNM stage. Disease-specific
      survival curves were compared. Univariate and multivariate analyses were used to
      examine the effects of each factor on survival over all sites and within each of
      3 sites. RESULTS: Univariate analysis of the combination of the 3 anatomic
      subsites showed survival with SpCC was worse than with conventional SCC (P <
      .001). Three-year disease-specific survival with SpCC was 49.5%, and 5-year
      disease-specific survival was 40.2%. Compared with conventional SCC, survival was
      worse for SpCC of the oral cavity (P < .001) and oropharynx (P < .001) but no
      different for the larynx and hypopharynx site (P = .15). Multivariate analysis
      identified age (P = .02), tumor size (P = .006), and M stage (P < .001) as the
      only variables significantly affecting survival with SpCC. All variables
      significantly affected survival with conventional SCC. CONCLUSIONS: Spindle cell
      carcinoma carries a worse prognosis than SCC. Larger tumor size, older age, and
      metastatic disease portend worse survival with SpCC of the head and neck.

PMID- 26203086
TI  - Prognostic Factors and Treatment Outcomes of Parotid Gland Cancer: A 10-Year
      Single-Center Experience.
AB  - OBJECTIVE: To investigate the treatment outcomes of parotid gland cancer at a
      single center over a 10-year period and to evaluate the prognostic significance
      of maximum standardized uptake value. STUDY DESIGN: Retrospective case series
      with chart review. SETTING: Academic care center. SUBJECTS AND METHODS: Ninety
      eight patients with primary parotid gland cancer who were surgically treated at
      Yonsei University Head & Neck Cancer Clinic between January 1999 and December
      2008 were analyzed. Patient data were collected retrospectively from medical
      charts. The investigators analyzed the association of clinicopathological factors
      and maximum standardized uptake value on (18)F-fluorodeoxyglucose positron
      emission tomography-computed tomography scan with disease-specific survival.
      RESULTS: Mean patient age was 49.7 years. Mean follow-up was 48.8 months. Thirty
      three, 40, 30, and 23 patients had stage I, II, III, and IVA disease,
      respectively. Mucoepidermoid carcinoma was the most common histologic type
      (34.7%), followed by acinic cell carcinoma (27.6%). Eighteen patients (18.4%)
      experienced recurrences (mean recurrence gap, 20.6 months; range, 2-87 months).
      Five- and 10-year disease-specific survival rates were 93.6% and 81.8%,
      respectively. In the univariate analysis, pathologic T stage, pathologic lymph
      node status, resection margin, external parenchymal extension, and maximum
      standardized uptake value were significantly associated with disease-specific
      survival. Pathologic lymph node status and maximum standardized uptake value were
      independent prognostic factors in the multivariate analysis. CONCLUSION: Our
      single-center experience with parotid gland cancer treatment is consistent with
      the literature. Cervical lymph node metastasis and high maximum standardized
      uptake value are associated with poor survival in parotid gland cancer.

PMID- 26203087
TI  - Effect of vaccinations on seizure risk and disease course in Dravet syndrome.
AB  - OBJECTIVE: To study the effect of vaccination-associated seizure onset on disease
      course and estimate the risk of subsequent seizures after infant pertussis
      combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome
      (DS). METHODS: We retrospectively analyzed data from hospital medical files,
      child health clinics, and the vaccination register for children with DS and
      pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell,
      acellular, or nonpertussis combination vaccination or within 5 to 12 days after
      MMR vaccination were defined as "vaccination-associated." Risks of vaccination
      associated seizures for the different vaccines were analyzed in univariable and
      in multivariable logistic regression for pertussis combination vaccines and by a
      self-controlled case series analysis using parental seizure registries for MMR
      vaccines. Disease courses of children with and without vaccination-associated
      seizure onset were compared. RESULTS: Children who had DS (n = 77) with and
      without vaccination-associated seizure onset (21% and 79%, respectively) differed
      in age at first seizure (median 3.7 vs 6.1 months, p < 0.001) but not in age at
      first nonvaccination-associated seizure, age at first report of developmental
      delay, or cognitive outcome. The risk of subsequent vaccination-associated
      seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18,
      95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11,
      95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self
      controlled case series analysis showed an increased incidence rate ratio of
      seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following
      MMR vaccination. CONCLUSIONS: Our results suggest that vaccination-associated
      earlier seizure onset does not alter disease course in DS, while the risk of
      subsequent vaccination-associated seizures is probably vaccine-specific.

PMID- 26203089
TI  - Retinal pathology in Susac syndrome detected by spectral-domain optical coherence
      tomography.
AB  - OBJECTIVE: The aim of this non-interventional study was to characterize retinal
      layer pathology in Susac syndrome (SuS), a disease with presumably autoimmune
      mediated microvessel occlusions in the retina, brain, and inner ear, in
      comparison to the most important differential diagnosis multiple sclerosis (MS).
      METHODS: Seventeen patients with SuS and 17 age- and sex-matched patients with
      relapsing-remitting MS (RRMS) and healthy controls (HC) were prospectively
      investigated by spectral-domain optical coherence tomography (OCT) including
      intraretinal layer segmentation in a multicenter study. Patients with SuS
      additionally received retinal fluorescein angiography (FA) and automated
      perimetry. RESULTS: Patchy thinning of the retinal nerve fiber layer, ganglion
      cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer
      compared to corresponding sectors in RRMS and HC eyes (p < 0.003 for SuS vs RRMS
      and HC) was observed in 23/34 (68%) SuS eyes, particularly in temporal quadrants.
      The outer nuclear layer (ONL) and photoreceptor layers (PRL) were not affected.
      FA performed in 15/17 patients with SuS was negative for disease-specific branch
      retinal artery occlusions in all but 1 eye at the time of OCT examination and
      revealed no additional vascular abnormalities, even in severely damaged OCT
      areas. In a subset of patients with SuS, associations of visual field data with
      distinct retinal layers were observed. CONCLUSION: Distinct OCT patterns of
      scattered, scar-like intraretinal pathology in SuS eyes, sparing the ONL and PRL,
      suggest a retinal, but not choroidal, vascular pathomechanism and clearly
      differentiate SuS from RRMS. Depending on the disease stage, OCT and FA provide
      specific complementary diagnostic information in SuS.

PMID- 26203090
TI  - Statins for poststroke seizures: the first antiepileptogenic agent?

PMID- 26203088
TI  - Migraine and risk of stroke in older adults: Northern Manhattan Study.
AB  - OBJECTIVE: To examine the association between migraine and stroke/vascular
      outcomes in a racially/ethnically diverse, older cohort. METHODS: Participants
      from the Northern Manhattan Study, a population-based cohort study of stroke
      incidence, were assessed for migraine symptoms using a self-report questionnaire
      based on criteria from the International Classification of Headache Disorders,
      second edition. We estimated the association between migraine and combined
      vascular events including stroke and stroke only over a mean follow-up of 11
      years, using Cox models adjusted for sociodemographic and vascular risk factors.
      RESULTS: Of 1,292 participants (mean age 68 +/- 9 years) with migraine data
      followed prospectively for vascular events, 262 patients (20%) had migraine and
      75 (6%) had migraine with aura. No association was found between migraine (with
      or without aura) and risk of either stroke or combined cardiovascular events.
      There was an interaction between migraine and current smoking (p = 0.02 in
      relation to stroke and p = 0.03 for combined vascular events), such that those
      with migraine and smoking were at an increased risk. The hazard ratio of stroke
      for migraine among current smokers was 3.17 (95% confidence interval [CI] 1.13
      8.85) and among current nonsmokers was 0.77 (95% CI 0.44-1.35). In relation to
      combined vascular events, the hazard ratio for migraine vs no migraine among
      current smokers was 1.83 (95% CI 0.89-3.75) and among current nonsmokers was 0.63
      (95% CI 0.43-0.94). CONCLUSION: In our racially/ethnically diverse population
      based cohort, migraine was associated with an increased risk of stroke among
      active smokers but not among nonsmokers.

PMID- 26203091
TI  - The autophagy-lysosomal pathway: General concepts and clinical implications.

PMID- 26203092
TI  - Statin treatment reduces the risk of poststroke seizures.
AB  - OBJECTIVE: To examine the potential efficacy of statin treatment in reducing the
      risk of poststroke seizures. METHODS: In this cohort study, patients with a first
      ever ischemic stroke and no history of epilepsy before stroke were enrolled.
      After a mean follow-up period of 2.5 years, a follow-up assessment was performed
      to identify poststroke epilepsy. Logistic regression and Cox regression analyses
      were used to assess the relationship between statin use and poststroke early
      onset seizures or poststroke epilepsy. RESULTS: Of 1,832 enrolled patients, 63
      (3.4%) patients had poststroke early-onset seizures and 91 (5.0%) patients had
      poststroke epilepsy. Statin use was associated with a lower risk of poststroke
      early-onset seizures (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.20
      0.60, p < 0.001), and this reduced risk was seen mainly in patients who used a
      statin only in the acute phase (OR 0.36, 95% CI 0.20-0.62, p < 0.001). No
      significant association was found between statin use and poststroke epilepsy (OR
      0.81, 95% CI 0.52-1.26, p = 0.349). In 63 patients who presented with early-onset
      seizures, statin use was associated with reduced risk of poststroke epilepsy (OR
      0.34, 95% CI 0.13-0.88, p = 0.026). CONCLUSIONS: Statin use, especially in the
      acute phase, may reduce the risk of poststroke early-onset seizures. In addition,
      statin treatment may prevent the progression of initial poststroke seizure
      induced neurodegeneration into chronic epilepsy. Because of the observational
      nature of the study, more studies are needed to confirm the results.
      CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in
      patients with a first-ever ischemic stroke, the early use of statins reduces the
      risk of early poststroke seizures.

PMID- 26203093
TI  - Diffuse leukoencephalopathy with spheroids presenting as primary progressive
      aphasia.

PMID- 26203095
TI  - Children Receiving Free or Reduced-Price School Lunch Have Higher Food
      Insufficiency Rates in Summer.
AB  - BACKGROUND: In 2012, 20% of households in the United States with children lacked
      consistent access to adequate food. Food insufficiency has significant
      implications for children, including poor physical and mental health outcomes,
      behavior problems, and low educational achievements. The National School Lunch
      Program (NSLP) is one policy solution to reduce food insufficiency among children
      from low-income families. OBJECTIVE: The objective of this project was to
      evaluate the association between NSLP participation and household food
      insufficiency by examining trajectories of food insufficiency over 10 calendar
      months. The calendar months included both nonsummer months when school is in
      session and summer months when school is out of session. METHODS: The study used
      the data from the Survey of Income and Program Participation and conducted linear
      growth curve analyses in the multilevel modeling context. Comparisons were made
      between the trajectories of food insufficiencies among recipients of free or
      reduced-price lunch and their counterparts who are eligible but choose not to
      participate in the program. RESULTS: Heads of households that included children
      receiving free or reduced-price lunch (n = 6867) were more likely to be female,
      black, unmarried, and unemployed, and have a lower educational attainment than
      those whose children were eligible but did not receive free or reduced-price
      lunch (n = 11,396). For households participating in the NSLP, the food
      insufficiency rate was consistent from January to May at ~4%, and then increased
      in June and July to >5%. Meanwhile, food insufficiency among eligible
      nonrecipients was constant throughout the year at nearly 2%. CONCLUSIONS: The
      NSLP protects households from food insufficiency. Policies should be instituted
      to make enrollment easier for households.

PMID- 26203094
TI  - Daily Zinc but Not Multivitamin Supplementation Reduces Diarrhea and Upper
      Respiratory Infections in Tanzanian Infants: A Randomized, Double-Blind, Placebo
      Controlled Clinical Trial.
AB  - BACKGROUND: Although various micronutrient regimens have been shown to prevent
      and treat common infectious diseases in children, the effects of daily
      multivitamin (MV) and/or zinc supplementation have not been widely evaluated in
      young African infants. OBJECTIVE: The objective was to determine whether daily
      supplementation of HIV-unexposed Tanzanian infants with MVs or zinc reduces the
      risk of infectious morbidity compared with placebo. METHODS: In a 2 * 2
      factorial, double-blind, randomized controlled trial, 2400 infants who were 6 wk
      of age and born to HIV-negative mothers in a low-malaria setting were randomly
      assigned to receive daily oral supplementation of MVs (vitamin B complex and
      vitamins C and E), zinc, zinc + MVs, or placebo for 18 mo. Morbidity was assessed
      by study nurses at monthly visits and by physicians every 3 mo and/or when the
      child was acutely ill. RESULTS: No significant differences were found in the
      percentage of nurse visits during which diarrhea, cough, or any other symptom
      were reported throughout the previous month when receiving either zinc or MVs.
      However, physician diagnoses of all types of diarrhea (RR = 0.88; 95% CI: 0.81,
      0.96; P = 0.003), dysentery (RR = 0.84; 95% CI: 0.74, 0.95; P = 0.006), and acute
      upper respiratory infection (RR = 0.92; 95% CI: 0.88, 0.97; P = 0.0005) were
      significantly lower for infants supplemented with zinc than for those who did not
      receive zinc. Among the 2360 infants for whom vital status was obtained, there
      was a nonsignificant increase in all-cause mortality among infants who received
      zinc (HR = 1.80; 95% CI: 0.98, 3.31; P = 0.06) compared with those who did not
      receive zinc. MVs did not alter the rates of any recorded physician diagnoses or
      mortality. Neither zinc nor MVs reduced hospitalizations or unscheduled
      outpatient visits. CONCLUSIONS: Daily zinc supplementation of Tanzanian infants
      beginning at the age of 6 wk may lower the burden of diarrhea and acute upper
      respiratory infections, but provision of MVs using the regimen in this trial did
      not confer additional benefit. This trial was registered at clinicaltrials.gov as
      NCT00421668.

PMID- 26203096
TI  - Obesity-Induced Inflammation Is Associated with Alterations in Subcellular Zinc
      Pools and Premature Mammary Gland Involution in Lactating Mice.
AB  - BACKGROUND: Lactation failure is common in overweight and obese women; however,
      the precise mechanism remains unknown. OBJECTIVE: We tested the hypothesis that
      obesity-induced inflammation in the mammary gland (MG) redistributes subcellular
      zinc pools to promote cell death of mammary epithelial cells (MECs) and premature
      involution. METHODS: Female DBA/2J mice were fed a high-fat (obese; 45% kcal from
      fat, n = 60) or control diet (lean; 10% kcal from fat, n = 50) for 5 wk and bred.
      MG cytokines and macrophage infiltration were determined by reverse transcriptase
      polymerase chain reaction and F4/80 staining, respectively. Zinc concentration
      was analyzed by atomic absorption spectroscopy, and zinc transporters and markers
      of endoplasmic reticulum (ER) stress, autophagy, and involution were measured by
      immunoblot. To confirm effects of inflammation, tumor necrosis factor-alpha (TNF)
      or vehicle was injected into adjacent MGs of lean lactating C57BL/6 mice (n = 5)
      and cultured MECs (HC11 cells) were treated with TNF in vitro. RESULTS: Seventy
      seven percent of obese mice failed to lactate (lean: 39%; P < 0.001). Obese mice
      capable of lactating had greater macrophage infiltration (obese: 135 +/- 40.4
      macrophages/mm(2); lean: 63.8 +/- 8.9 macrophages/mm(2); P < 0.001) and elevated
      TNF expression (P < 0.05), concurrent with lower zrt- irt-like protein 7
      abundance (P < 0.05) and higher ER zinc concentration (obese: 0.36 +/- 0.004 MUg
      Zn/mg protein; lean: 0.30 +/- 0.02 MUg Zn/mg protein; P < 0.05) compared with
      lean mice. Heat shock protein 5 (HSPA5) expression (P < 0.05) was suppressed in
      the MG of obese mice, which was consistent with HSPA5 suppression in TNF-injected
      MGs (P < 0.01) and MECs treated with TNF in vitro (P < 0.01). Moreover, obesity
      increased lysosomal activity (P < 0.05) and autophagy in the MG, which
      corresponded to increased zinc transporter 2 abundance and lysosomal zinc
      concentration compared with lean mice (obese: 0.20 +/- 0.02 MUg Zn/mg protein;
      lean: 0.14 +/- 0.01 MUg Zn/mg protein; P < 0.05). Importantly, MGs of obese mice
      exhibited markers of apoptosis (P = 0.05) and involution (P < 0.01), which were
      not observed in lean mice. CONCLUSIONS: Diet-induced obesity created a
      proinflammatory MG microenvironment in mice, which was associated with zinc
      mediated ER stress and autophagy and the activation of premature involution.

PMID- 26203097
TI  - Dietary Intakes of Folic Acid and Methionine in Early Childhood Are Associated
      with Body Composition at School Age.
AB  - BACKGROUND: Deficiency of vitamin B-6, vitamin B-12, folate, folic acid, or
      methionine may lead to dysregulation of DNA methylation, which might lead to
      disturbed energy and lipid metabolism. OBJECTIVE: We aimed to explore whether
      intakes of vitamin B-6, vitamin B-12, folate, folic acid, and methionine at 1 y
      are associated with measures of growth and body composition at the age of 6 y.
      METHODS: This study was performed in 2922 children participating in The
      Generation R Study, a population-based prospective cohort study. Dietary intakes
      of vitamins B-6 and B-12, folate, folic acid, and methionine were assessed at a
      median age of 12.9 mo by using a validated food-frequency questionnaire. At the
      age of 6 y, height and weight were measured, and body mass index (BMI; in
      kg/m(2)) was calculated. Body fat was measured with dual-energy X-ray
      absorptiometry, and body fat percentage and the ratio of android fat mass to
      gynoid fat mass (android:gynoid) were calculated. RESULTS: In models adjusted for
      maternal and child characteristics, children with folic acid intakes in the
      highest tertile had a 0.16 SD score (SDS) lower weight (95% CI: -0.31, -0.02 SDS)
      and a 0.14 SDS lower BMI (95% CI: -0.26, -0.01 SDS) than children in the lowest
      tertile. Children with vitamin B-12 intakes in the highest tertile had a 0.13 SDS
      higher android:gynoid (95% CI: 0.00, 0.25 SDS) than children in the lowest
      tertile. In addition, children with intakes in the highest tertile of methionine
      had a 0.09 SDS higher BMI (95% CI: 0.01, 0.17) and a 0.12 SDS higher
      android:gynoid (95% CI: 0.02, 0.22) than children in the lowest tertile. Vitamin
      B-6 and folate intakes were not associated with any of the body composition
      outcomes measured. CONCLUSIONS: In this population of children, early high folic
      acid intakes were associated with a lower body weight and BMI at the age of 6 y.
      In contrast, early higher methionine intakes were associated with unfavorable
      body composition at the age of 6 y. Future studies should investigate long-term
      consequences of these outcomes on health.

PMID- 26203098
TI  - Iodine Supplementation Decreases Hypercholesterolemia in Iodine-Deficient,
      Overweight Women: A Randomized Controlled Trial.
AB  - BACKGROUND: In iodine deficiency, thyrotropin (TSH) may increase to stimulate
      thyroidal iodine uptake. In iodine-sufficient populations, higher TSH predicts
      higher total cholesterol. Whether higher TSH caused by iodine deficiency affects
      serum lipids is uncertain. OBJECTIVE: Our aim was to determine if iodine
      repletion decreases serum TSH and improves the lipid profile. METHODS: In this
      randomized controlled intervention, iodine-deficient, overweight or obese
      Moroccan women (n = 163) received 200 MUg oral iodine or a placebo daily for 6
      mo. Main outcomes were serum TSH and plasma total and LDL cholesterol. Secondary
      outcomes included thyroid hormones and measures of lipid and glucose metabolism
      and urinary iodine concentration (UIC). Data were compared by using mixed-model
      analysis. RESULTS: In the intervention group, median UIC increased from 38 (95%
      CI: 34, 45) MUg/L to 77 (95% CI: 59, 89) MUg/L (P < 0.001). After 6 mo of
      intervention, TSH was 33% lower in the treatment group than in the placebo group
      (P = 0.024). The triiodothyronine (T3) to thyroxine (T4) ratio and thyroglobulin
      decreased with treatment [-15% (P = 0.002) and -32% (P < 0.001), respectively],
      whereas T4 concentrations were higher in the treatment group (P < 0.001). Total
      cholesterol in subjects with elevated baseline cholesterol (>5 mmol/L) was
      reduced by 11% after the intervention (P = 0.034). At 6 mo, only 21.5% of treated
      women remained hypercholesterolemic (total cholesterol >5 mmol/L) vs. 34.8% of
      controls (baseline: 44.2% in the intervention and 36.8% in the control group; P =
      0.015). The reduction in the prevalence of elevated LDL cholesterol (>3 mmol/L)
      in the intervention group (50.6% to 35.4% compared with 47.4% to 44.9% in the
      control group) was not significant (P-interaction = 0.23). CONCLUSIONS: Our
      findings suggest that moderate to severe iodine deficiency in overweight women
      elevates serum TSH and produces a more atherogenic lipid profile and that iodine
      supplementation in this group reduces the prevalence of hypercholesterolemia.
      Thus, iodine prophylaxis may reduce cardiovascular disease risk in overweight
      adults. This trial was registered at clinicaltrials.gov as NCT01985204.

PMID- 26203099
TI  - Agave Inulin Supplementation Affects the Fecal Microbiota of Healthy Adults
      Participating in a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.
AB  - BACKGROUND: Prebiotics resist digestion, providing fermentable substrates for
      select gastrointestinal bacteria associated with health and well-being. Agave
      inulin differs from other inulin type fibers in chemical structure and botanical
      origin. Preclinical animal research suggests these differences affect bacterial
      utilization and physiologic outcomes. Thus, research is needed to determine
      whether these effects translate to healthy adults. OBJECTIVE: We evaluated agave
      inulin utilization by the gastrointestinal microbiota by measuring fecal
      fermentative end products and bacterial taxa. METHODS: A randomized, double
      blind, placebo-controlled, 3-period, crossover trial was undertaken in healthy
      adults (n = 29). Participants consumed 0, 5.0, or 7.5 g agave inulin/d for 21 d
      with 7-d washouts between periods. Participants recorded daily dietary intake;
      fecal samples were collected during days 16-20 of each period and were subjected
      to fermentative end product analysis and 16S Illumina sequencing. RESULTS: Fecal
      Actinobacteria and Bifidobacterium were enriched (P < 0.001) 3- and 4-fold after
      5.0 and 7.5 g agave inulin/d, respectively, compared with control. Desulfovibrio
      were depleted 40% with agave inulin compared with control. Agave inulin tended (P
      < 0.07) to reduce fecal 4-methyphenol and pH. Bivariate correlations revealed a
      positive association between intakes of agave inulin (g/kcal) and Bifidobacterium
      (r = 0.41, P < 0.001). Total dietary fiber intake (total fiber plus 0, 5.0, or
      7.5 g agave inulin/d) per kilocalorie was positively associated with fecal
      butyrate (r = 0.30, P = 0.005), tended to be positively associated with
      Bifidobacterium (r = 0.19, P = 0.08), and was negatively correlated with
      Desulfovibrio abundance (r = -0.31, P = 0.004). CONCLUSIONS: Agave inulin
      supplementation shifted the gastrointestinal microbiota composition and activity
      in healthy adults. Further investigation is warranted to determine whether the
      observed changes translate into health benefits in human populations. This trial
      was registered at clinicaltrials.gov as NCT01925560.

PMID- 26203100
TI  - Amino Acid Intakes Are Inversely Associated with Arterial Stiffness and Central
      Blood Pressure in Women.
AB  - BACKGROUND: Although data suggest that intakes of total protein and specific
      amino acids (AAs) reduce blood pressure, data on other cardiovascular disease
      risk factors are limited. OBJECTIVE: We examined associations between intakes of
      AAs with known mechanistic links to cardiovascular health and direct measures of
      arterial stiffness, central blood pressure, and atherosclerosis. METHODS: In a
      cross-sectional study of 1898 female twins aged 18-75 y from the TwinsUK
      registry, intakes of 7 cardioprotective AAs (arginine, cysteine, glutamic acid,
      glycine, histidine, leucine, and tyrosine) were calculated from food-frequency
      questionnaires. Direct measures of arterial stiffness and atherosclerosis
      included central systolic blood pressure (cSBP), mean arterial pressure (MAP),
      augmentation index (AI), pulse wave velocity (PWV), and intima-media thickness
      (IMT). ANCOVA was used to assess the associations between endpoints of arterial
      stiffness and intake (per quintile), adjusting for potential confounders.
      RESULTS: In multivariable analyses, higher intakes of total protein and 7
      potentially cardioprotective AAs were associated with lower cSBP, MAP, and PWV.
      Higher intakes of glutamic acid, leucine, and tyrosine were most strongly
      associated with PWV, with respective differences of -0.4 +/- 0.2 m/s (P-trend =
      0.02), -0.4 +/- 0.2 m/s (P-trend = 0.03), and -0.4 +/- 0.2 m/s (P-trend = 0.03),
      comparing extreme quintiles. There was a significant interaction between AA
      intakes and protein source, and higher intakes of AAs from vegetable sources were
      associated with lower central blood pressure and AI. Higher intakes of glutamic
      acid, leucine, and tyrosine from animal sources were associated with lower PWV.
      CONCLUSIONS: These data provide evidence to suggest that intakes of several AAs
      are associated with cardiovascular benefits beyond blood pressure reduction in
      healthy women. The magnitude of the observed associations was similar to those
      previously reported for other lifestyle factors. Increasing intakes of these AAs
      could be an important and readily achievable way to reduce cardiovascular disease
      risk.

PMID- 26203101
TI  - Authors' response: A systematic review of the association between pleural plaques
      and changes in lung function.

PMID- 26203102
TI  - The optimal neural strategy for a stable motor task requires a compromise between
      level of muscle cocontraction and synaptic gain of afferent feedback.
AB  - Increasing joint stiffness by cocontraction of antagonist muscles and
      compensatory reflexes are neural strategies to minimize the impact of unexpected
      perturbations on movement. Combining these strategies, however, may compromise
      steadiness, as elements of the afferent input to motor pools innervating
      antagonist muscles are inherently negatively correlated. Consequently, a high
      afferent gain and active contractions of both muscles may imply negatively
      correlated neural drives to the muscles and thus an unstable limb position. This
      hypothesis was systematically explored with a novel computational model of the
      peripheral nervous system and the mechanics of one limb. Two populations of motor
      neurons received synaptic input from descending drive, spinal interneurons, and
      afferent feedback. Muscle force, simulated based on motor unit activity,
      determined limb movement that gave rise to afferent feedback from muscle spindles
      and Golgi tendon organs. The results indicated that optimal steadiness was
      achieved with low synaptic gain of the afferent feedback. High afferent gains
      during cocontraction implied increased levels of common drive in the motor neuron
      outputs, which were negatively correlated across the two populations,
      constraining instability of the limb. Increasing the force acting on the joint
      and the afferent gain both effectively minimized the impact of an external
      perturbation, and suboptimal adjustment of the afferent gain could be compensated
      by muscle cocontraction. These observations show that selection of the strategy
      for a given contraction implies a compromise between steadiness and effectiveness
      of compensations to perturbations. This indicates that a task-dependent selection
      of neural strategy for steadiness is necessary when acting in different
      environments. 

PMID- 26203105
TI  - A recording chamber for small volume slice electrophysiology.
AB  - Electrophysiological recordings from brain slices are typically performed in
      small recording chambers that allow for the superfusion of the tissue with
      artificial extracellular solution (ECS), while the chamber holding the tissue is
      mounted in the optical path of a microscope to image neurons in the tissue. ECS
      itself is inexpensive, and thus superfusion rates and volumes of ECS consumed
      during an experiment using standard ECS are not critical. However, some
      experiments require the addition of expensive pharmacological agents or other
      chemical compounds to the ECS, creating a need to build superfusion systems that
      operate on small volumes while still delivering appropriate amounts of oxygen and
      other nutrients to the tissue. We developed a closed circulation tissue chamber
      for slice recordings that operates with small volumes of bath solution in the
      range of 1.0 to 2.6 ml and a constant oxygen/carbon dioxide delivery to the
      solution in the bath. In our chamber, the ECS is oxygenated and recirculated
      directly in the recording chamber, eliminating the need for tubes and external
      bottles/containers to recirculate and bubble ECS and greatly reducing the total
      ECS volume required for superfusion. At the same time, the efficiency of tissue
      oxygenation and health of the section are comparable to standard superfusion
      methods. We also determined that the small volume of ECS contains a sufficient
      amount of nutrients to support the health of a standard brain slice for several
      hours without concern for either depletion of nutrients or accumulation of waste
      products. 

PMID- 26203104
TI  - Differential encoding of spatial information among retinal on cone bipolar cells.
AB  - The retina is the first stage of visual processing. It encodes elemental features
      of visual scenes. Distinct cone bipolar cells provide the substrate for this to
      occur. They encode visual information, such as color and luminance, a principle
      known as parallel processing. Few studies have directly examined whether
      different forms of spatial information are processed in parallel among cone
      bipolar cells. To address this issue, we examined the spatial information encoded
      by mouse ON cone bipolar cells, the subpopulation excited by increments in
      illumination. Two types of spatial processing were identified. We found that ON
      cone bipolar cells with axons ramifying in the central inner plexiform layer were
      tuned to preferentially encode small stimuli. By contrast, ON cone bipolar cells
      with axons ramifying in the proximal inner plexiform layer, nearest the ganglion
      cell layer, were tuned to encode both small and large stimuli. This dichotomy in
      spatial tuning is attributable to amacrine cells providing stronger inhibition to
      central ON cone bipolar cells compared with proximal ON cone bipolar cells.
      Furthermore, background illumination altered this difference in spatial tuning.
      It became less pronounced in bright light, as amacrine cell-driven inhibition
      became pervasive among all ON cone bipolar cells. These results suggest that
      differential amacrine cell input determined the distinct spatial encoding
      properties among ON cone bipolar cells. These findings enhance the known parallel
      processing capacity of the retina. 

PMID- 26203103
TI  - An integrative role for the superior colliculus in selecting targets for
      movements.
AB  - A fundamental goal of systems neuroscience is to understand the neural mechanisms
      underlying decision making. The midbrain superior colliculus (SC) is known to be
      central to the selection of one among many potential spatial targets for
      movements, which represents an important form of decision making that is
      tractable to rigorous experimental investigation. In this review, we first
      discuss data from mammalian models-including primates, cats, and rodents-that
      inform our understanding of how neural activity in the SC underlies the selection
      of targets for movements. We then examine the anatomy and physiology of inputs to
      the SC from three key regions that are themselves implicated in motor decisions
      the basal ganglia, parabrachial region, and neocortex-and discuss how they may
      influence SC activity related to target selection. Finally, we discuss the
      potential for methodological advances to further our understanding of the neural
      bases of target selection. Our overarching goal is to synthesize what is known
      about how the SC and its inputs act together to mediate the selection of targets
      for movements, to highlight open questions about this process, and to spur future
      studies addressing these questions. 

PMID- 26203106
TI  - Role of the retrotrapezoid nucleus/parafacial respiratory group in coughing and
      swallowing in guinea pigs.
AB  - The retrotrapezoid/parafacial respiratory group (RTN/pFRG) located ventral to the
      facial nucleus plays a key role in regulating breathing, especially enhanced
      expiratory activity during hypercapnic conditions. To clarify the roles of the
      RTN/pFRG region in evoking coughing, during which reflexive enhanced expiration
      is produced, and in swallowing, during which the expiratory activity is
      consistently halted, we recorded extracellular activity from RTN/pFRG neurons
      during these fictive behaviors in decerebrate, paralyzed, and artificially
      ventilated guinea pigs. The activity of the majority of recorded respiratory
      neurons was changed in synchrony with coughing and swallowing. To further
      evaluate the contribution of RTN/pFRG neurons to these nonrespiratory behaviors,
      the motor output patterns during breathing, coughing, and swallowing were
      compared before and after brain stem transection at the caudal margin of RTN/pFRG
      region. In addition, the effects of transection at its rostral margin were also
      investigated to evaluate pontine contribution to these behaviors. During
      respiration, transection at the rostral margin attenuated the postinspiratory
      activity of the recurrent laryngeal nerve. Meanwhile, the late expiratory
      activity of the abdominal nerve was abolished after caudal transection. The
      caudal transection also decreased the amplitude of the coughing-related abdominal
      nerve discharge but did not abolish the activity. Swallowing could be elicited
      even after the caudal end transection. These findings raise the prospect that the
      RTN/pFRG contributes to expiratory regulation during normal respiration, although
      this region is not an essential element of the neuronal networks involved in
      coughing and swallowing. 

PMID- 26203107
TI  - The transformation of synaptic to system plasticity in motor output from the
      sacral cord of the adult mouse.
AB  - Synaptic plasticity is fundamental in shaping the output of neural networks. The
      transformation of synaptic plasticity at the cellular level into plasticity at
      the system level involves multiple factors, including behavior of local networks
      of interneurons. Here we investigate the synaptic to system transformation for
      plasticity in motor output in an in vitro preparation of the adult mouse spinal
      cord. System plasticity was assessed from compound action potentials (APs) in
      spinal ventral roots, which were generated simultaneously by the axons of many
      motoneurons (MNs). Synaptic plasticity was assessed from intracellular recordings
      of MNs. A computer model of the MN pool was used to identify the middle steps in
      the transformation from synaptic to system behavior. Two input systems that
      converge on the same MN pool were studied: one sensory and one descending. The
      two synaptic input systems generated very different motor outputs, with sensory
      stimulation consistently evoking short-term depression (STD) whereas descending
      stimulation had bimodal plasticity: STD at low frequencies but short-term
      facilitation (STF) at high frequencies. Intracellular and pharmacological studies
      revealed contributions from monosynaptic excitation and stimulus time-locked
      inhibition but also considerable asynchronous excitation sustained from local
      network activity. The computer simulations showed that STD in the monosynaptic
      excitatory input was the primary driver of the system STD in the sensory input
      whereas network excitation underlies the bimodal plasticity in the descending
      system. These results provide insight on the roles of plasticity in the
      monosynaptic and polysynaptic inputs converging on the same MN pool to overall
      motor plasticity. 

PMID- 26203108
TI  - Inducing hindlimb locomotor recovery in adult rat after complete thoracic spinal
      cord section using repeated treadmill training with perineal stimulation only.
AB  - Although a complete thoracic spinal cord section in various mammals induces
      paralysis of voluntary movements, the spinal lumbosacral circuitry below the
      lesion retains its ability to generate hindlimb locomotion. This important
      capacity may contribute to the overall locomotor recovery after partial spinal
      cord injury (SCI). In rats, it is usually triggered by pharmacological and/or
      electrical stimulation of the cord while a robot sustains the animals in an
      upright posture. In the present study we daily trained a group of adult spinal
      (T7) rats to walk with the hindlimbs for 10 wk (10 min/day for 5 days/wk), using
      only perineal stimulation. Kinematic analysis and terminal electromyographic
      recordings revealed a strong effect of training on the reexpression of hindlimb
      locomotion. Indeed, trained animals gradually improved their locomotion while
      untrained animals worsened throughout the post-SCI period. Kinematic parameters
      such as averaged and instant swing phase velocity, step cycle variability, foot
      drag duration, off period duration, and relationship between the swing features
      returned to normal values only in trained animals. The present results clearly
      demonstrate that treadmill training alone, in a normal horizontal posture,
      elicited by noninvasive perineal stimulation is sufficient to induce a persistent
      hindlimb locomotor recovery without the need for more complex strategies. This
      provides a baseline level that should be clearly surpassed if additional
      locomotor-enabling procedures are added. Moreover, it has a clinical value since
      intrinsic spinal reorganization induced by training should contribute to improve
      locomotor recovery together with afferent feedback and supraspinal modifications
      in patients with incomplete SCI. 

PMID- 26203109
TI  - Multineuronal activity patterns identify selective synaptic connections under
      realistic experimental constraints.
AB  - Structured multineuronal activity patterns within local neocortical circuitry are
      strongly linked to sensory input, motor output, and behavioral choice. These
      reliable patterns of pairwise lagged firing are the consequence of connectivity
      since they are not present in rate-matched but unconnected Poisson nulls. It is
      important to relate multineuronal patterns to their synaptic underpinnings, but
      it is unclear how effectively statistical dependencies in spiking between neurons
      identify causal synaptic connections. To assess the feasibility of mapping
      function onto structure we used a network model that showed a diversity of
      multineuronal activity patterns and replicated experimental constraints on data
      acquisition. Using an iterative Bayesian inference algorithm, we detected a
      select subset of monosynaptic connections substantially more precisely than
      correlation-based inference, a common alternative approach. We found that precise
      inference of synaptic connections improved with increasing numbers of diverse
      multineuronal activity patterns in contrast to increased observations of a single
      pattern. Surprisingly, neuronal spiking was most effective and precise at
      revealing causal synaptic connectivity when the lags considered by the iterative
      Bayesian algorithm encompassed the timescale of synaptic conductance and
      integration (~10 ms), rather than synaptic transmission time (~2 ms),
      highlighting the importance of synaptic integration in driving postsynaptic
      spiking. Last, strong synaptic connections were detected preferentially,
      underscoring their special importance in cortical computation. Even after
      simulating experimental constraints, top down approaches to cortical
      connectivity, from function to structure, identify synaptic connections
      underlying multineuronal activity. These select connections are closely tied to
      cortical processing. 

PMID- 26203110
TI  - Syntaxin 1B is important for mouse postnatal survival and proper synaptic
      function at the mouse neuromuscular junctions.
AB  - STX1 is a major neuronal syntaxin protein located at the plasma membrane of the
      neuronal tissues. Rodent STX1 has two highly similar paralogs, STX1A and STX1B,
      that are thought to be functionally redundant. Interestingly, some studies have
      shown that the distribution patterns of STX1A and STX1B at the central and
      peripheral nervous systems only partially overlapped, implying that there might
      be differential functions between these paralogs. In the current study, we
      generated an STX1B knockout (KO) mouse line and studied the impact of STX1B
      removal in neurons of several brain regions and the neuromuscular junction (NMJ).
      We found that either complete removal of STX1B or selective removal of it from
      forebrain excitatory neurons in mice caused premature death. Autaptic hippocampal
      and striatal cultures derived from STX1B KO mice still maintained efficient
      neurotransmission compared with neurons from STX1B wild-type and heterozygous
      mice. Interestingly, examining high-density cerebellar cultures revealed a
      decrease in the spontaneous GABAergic transmission frequency, which was most
      likely due to a lower number of neurons in the STX1B KO cultures, suggesting that
      STX1B is essential for neuronal survival in vitro. Moreover, our study also
      demonstrated that although STX1B is dispensable for the formation of the mouse
      NMJ, it is required to maintain the efficiency of neurotransmission at the nerve
      muscle synapse. 

PMID- 26203112
TI  - Noradrenergic refinement of glutamatergic neuronal circuits in the lateral
      superior olivary nucleus before hearing onset.
AB  - Neuronal circuit plasticity during development is fundamental for precise network
      formation. Pioneering studies of the developmental visual cortex indicated that
      noradrenaline (NA) is crucial for ocular dominance plasticity during the critical
      period in the visual cortex. Recent research demonstrated tonotopic map formation
      by NA during the critical period in the auditory system, indicating that NA also
      contributes to synaptic plasticity in this system. The lateral superior olive
      (LSO) in the auditory system receives glutamatergic input from the ventral
      cochlear nucleus (VCN) and undergoes circuit remodeling during postnatal
      development. LSO is innervated by noradrenergic afferents and is therefore a
      suitable model to study the function of NA in refinement of neuronal circuits.
      Chemical lesions of the noradrenergic system and chronic inhibition of alpha2
      adrenoceptors in vivo during postnatal development in mice disrupted functional
      elimination and strengthening of VCN-LSO afferents. This was potentially mediated
      by activation of presynaptic alpha2-adrenoceptors and inhibition of glutamate
      release because NA presynaptically suppressed excitatory postsynaptic current
      (EPSC) through alpha2-adrenoceptors during the first two postnatal weeks in an in
      vitro study. Furthermore, NA and alpha2-adrenoceptor agonist induced long-term
      suppression of EPSCs and decreased glutamate release. These results suggest that
      NA has a critical role in synaptic refinement of the VCN-LSO glutamatergic
      pathway through failure of synaptic transmission. Because of the ubiquitous
      distribution of NA afferents and the extensive expression of alpha2-adrenoceptors
      throughout the immature brain, this phenomenon might be widespread in the
      developing central nervous system. 

PMID- 26203111
TI  - Functional connectivity in raphe-pontomedullary circuits supports active
      suppression of breathing during hypocapnic apnea.
AB  - Hyperventilation is a common feature of disordered breathing. Apnea ensues if CO2
      drive is sufficiently reduced. We tested the hypothesis that medullary raphe,
      ventral respiratory column (VRC), and pontine neurons have functional
      connectivity and persistent or evoked activities appropriate for roles in the
      suppression of drive and rhythm during hyperventilation and apnea. Phrenic nerve
      activity, arterial blood pressure, end-tidal CO2, and other parameters were
      monitored in 10 decerebrate, vagotomized, neuromuscularly-blocked, and
      artificially ventilated cats. Multielectrode arrays recorded spiking activity of
      649 neurons. Loss and return of rhythmic activity during passive hyperventilation
      to apnea were identified with the S-transform. Diverse fluctuating activity
      patterns were recorded in the raphe-pontomedullary respiratory network during the
      transition to hypocapnic apnea. The firing rates of 160 neurons increased during
      apnea; the rates of 241 others decreased or stopped. VRC inspiratory neurons were
      usually the last to cease firing or lose rhythmic activity during the transition
      to apnea. Mayer wave-related oscillations (0.04-0.1 Hz) in firing rate were also
      disrupted during apnea. Four-hundred neurons (62%) were elements of pairs with at
      least one hyperventilation-responsive neuron and a correlational signature of
      interaction identified by cross-correlation or gravitational clustering. Our
      results support a model with distinct groups of chemoresponsive raphe neurons
      contributing to hypocapnic apnea through parallel processes that incorporate
      disfacilitation and active inhibition of inspiratory motor drive by expiratory
      neurons. During apnea, carotid chemoreceptors can evoke rhythm reemergence and an
      inspiratory shift in the balance of reciprocal inhibition via suppression of
      ongoing tonic expiratory neuron activity. 

PMID- 26203113
TI  - Adaptation and aftereffects of split-belt walking in cerebellar lesion patients.
AB  - To walk efficiently and stably on different surfaces under various constrained
      conditions, humans need to adapt their gait pattern substantially. Although the
      mechanisms behind locomotor adaptation are still not fully understood, the
      cerebellum is thought to play an important role. In this study we aimed to
      address the specific localization of cerebellar involvement in split-belt
      adaptation by comparing performance in patients with stable focal lesions after
      cerebellar tumor resection and in healthy controls. We observed that changes in
      symmetry of those parameters that were most closely related to interlimb
      coordination (such as step length and relative double stance time) were similar
      between healthy controls and cerebellar patients during and after split-belt
      walking. In contrast, relative stance times (proportions of stance in the gait
      cycle) were more asymmetric for the patient group than for the control group
      during the early phase of the post-split-belt condition. Patients who walked with
      more asymmetric relative stance times were more likely to demonstrate lesions in
      vermal lobules VI and Crus II. These results confirm that deficits in gait
      adaptation vary with ataxia severity and between patients with different types of
      cerebellar damage. 

PMID- 26203114
TI  - Gait asymmetry during early split-belt walking is related to perception of belt
      speed difference.
AB  - Gait adaptation is essential for humans to walk according to the different
      demands of the environment. Although locomotor adaptation has been studied in
      different contexts and in various patient populations, the mechanisms behind
      locomotor adaptation are still not fully understood. The aim of the present study
      was to test two opposing hypotheses about the control of split-belt walking, one
      based on avoidance of limping and the other on avoiding limb excursion asymmetry.
      We assessed how well cerebellar patients with focal lesions and healthy control
      participants could sense differences between belt speeds during split-belt
      treadmill walking and correlated this to split-belt adaptation parameters. The
      ability to perceive differences between belt speeds was similar between the
      cerebellar patients and the healthy controls. After combining all participants,
      we observed a significant inverse correlation between stance time symmetry and
      limb excursion symmetry during the early phase of split-belt walking.
      Participants who were better able to perceive belt speed differences (e.g., they
      had a lower threshold and hence were able to detect a smaller speed difference)
      walked with the smallest asymmetry in stance time and the largest asymmetry in
      limb excursion. Our data support the hypothesis that humans aim to minimize
      (temporal) limping rather than (spatial) limb excursion asymmetry when using
      their perception of belt speed differences in the early phase of adaptation to
      split-belt walking. 

PMID- 26203115
TI  - Neural substrates of sensorimotor processes: letter writing and letter
      perception.
AB  - Writing and perceiving letters are thought to share similar neural substrates;
      however, what constitutes a neural representation for letters is currently
      debated. One hypothesis is that letter representation develops from sensorimotor
      experience resulting in an integrated set of modality-specific regions, whereas
      an alternative account suggests that letter representations may be abstract,
      independent of modality. Studies reviewed suggest that letter representation
      consists of a network of modality-responsive brain regions that may include an
      abstract component. 

PMID- 26203116
TI  - Prevalence of human papillomavirus infection in a clinic sample of transsexuals
      in Italy.
AB  - OBJECTIVES: Detectable human papillomavirus (HPV) DNA is the most common sexually
      transmitted infection. Reports on the prevalence of detectable HPV DNA among
      transsexuals (not sex workers) are scarce. The objective of the study was to
      determine the prevalence of detectable HPV DNA in a clinic sample of transsexuals
      and to assess the relationship between detectable HPV DNA and cytological
      outcomes. METHODS: Clinical samples (oral, anal, vaginal, cervicovaginal and
      penile scraped cells) from 35 transsexuals (surgically treated and surgically
      untreated) who attended the outpatient Clinic of Gender Identity Dysphoria of the
      Department of Obstetrics and Gynecology of Policlinico Hospital (Bari, Italy)
      were collected for cytological analysis and HPV DNA detection and typing. All
      enrolled subjects answered an anonymous structured questionnaire about their
      sexual habits. Serological status for other sexually transmitted diseases
      (hepatitis B virus (HBV), hepatitis C virus (HCV), HIV and syphilis) was also
      evaluated. RESULTS: HPV DNA was detected in 14 of 35 patients (40.0%). The
      prevalence of detectable HPV DNA was 38.2% (13/34) in tested anal samples, 9.1%
      (2/22) in vaginal samples and 8.3% (1/12) in penile samples. Oncogenic HPV
      genotypes have been detected in 93% of HPV-positive transsexuals. More than one
      third (35.7%) of HPV-positive transsexuals were infected with at least one of the
      four vaccine-preventable genotypes, 6, 11, 16 and 18. CONCLUSIONS: The high rate
      of detectable HPV DNA by oncogenic types suggests that periodic cytological
      screening and clinical evaluation may be necessary since transsexuals are at high
      risk of anogenital cancer. Also promoting HPV vaccination in younger subjects may
      be advisable.

PMID- 26203117
TI  - NADPH Oxidase 4 at the Nexus of Diabetes, Reactive Oxygen Species, and Renal
      Metabolism.

PMID- 26203118
TI  - Metabolomics Reveals a Key Role for Fumarate in Mediating the Effects of NADPH
      Oxidase 4 in Diabetic Kidney Disease.
AB  - The NADPH oxidase (NOX) isoform NOX4 has been linked with diabetic kidney disease
      (DKD). However, a mechanistic understanding of the downstream effects of NOX4
      remains to be established. We report that podocyte-specific induction of NOX4 in
      vivo was sufficient to recapitulate the characteristic glomerular changes noted
      with DKD, including glomerular hypertrophy, mesangial matrix accumulation,
      glomerular basement membrane thickening, albuminuria, and podocyte dropout.
      Intervention with a NOX1/NOX4 inhibitor reduced albuminuria, glomerular
      hypertrophy, and mesangial matrix accumulation in the F1 Akita model of DKD.
      Metabolomic analyses from these mouse studies revealed that tricarboxylic acid
      (TCA) cycle-related urinary metabolites were increased in DKD, but fumarate
      levels were uniquely reduced by the NOX1/NOX4 inhibitor. Expression of fumarate
      hydratase (FH), which regulates urine fumarate accumulation, was reduced in the
      diabetic kidney (in mouse and human tissue), and administration of the NOX1/NOX4
      inhibitor increased glomerular FH levels in diabetic mice. Induction of Nox4 in
      vitro and in the podocyte-specific NOX4 transgenic mouse led to reduced FH
      levels. In vitro, fumarate stimulated endoplasmic reticulum stress, matrix gene
      expression, and expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and
      TGF-beta. Similar upregulation of renal HIF-1alpha and TGF-beta expression was
      observed in NOX4 transgenic mice and diabetic mice and was attenuated by
      NOX1/NOX4 inhibition in diabetic mice. In conclusion, NOX4 is a major mediator of
      diabetes-associated glomerular dysfunction through targeting of renal FH, which
      increases fumarate levels. Fumarate is therefore a key link connecting metabolic
      pathways to DKD pathogenesis, and measuring urinary fumarate levels may have
      application for monitoring renal NOX4 activity. 

PMID- 26203120
TI  - Rate Constants of PSII Photoinhibition and its Repair, and PSII Fluorescence
      Parameters in Field Plants in Relation to their Growth Light Environments.
AB  - The extent of photoinhibition of PSII is determined by a balance between the rate
      of photodamage to PSII and that of repair of the damaged PSII. It has already
      been indicated that the rate constants of photodamage (kpi) and repair (krec) of
      the leaves differ depending on their growth light environment. However, there are
      no studies using plants in the field. We examined these rate constants and
      fluorescence parameters of several field-grown plants to determine inter
      relationships between these values and the growth environment. The kpi values
      were strongly related to the excess energy, EY, of the puddle model and non
      regulated energy dissipation, Y(NO), of the lake model, both multiplied by the
      photosynthetically active photon flux density (PPFD) level during the
      photoinhibitory treatment. In contrast, the krec values corrected against in situ
      air temperature were very strongly related to the daily PPFD level. The plants
      from the fields showed higher NPQ than the chamber-grown plants, probably because
      these field plants acclimated to stronger lightflecks than the averaged growth
      PPFD. Comparing chamber-grown plants and the field plants, we showed that kpi is
      determined by the incident light level and the photosynthetic capacities such as
      in situ rate of PSII electron transport and non-photochemical quenching (NPQ)
      [e.g. Y(NO)*PPFD] and that krec is mostly determined by the growth light and
      temperature levels. 

PMID- 26203119
TI  - Plants Possess a Cyclic Mitochondrial Metabolic Pathway similar to the Mammalian
      Metabolic Repair Mechanism Involving Malate Dehydrogenase and l-2
      Hydroxyglutarate Dehydrogenase.
AB  - Enzymatic side reactions can give rise to the formation of wasteful and toxic
      products that are removed by metabolite repair pathways. In this work, we
      identify and characterize a mitochondrial metabolic repair mechanism in
      Arabidopsis thaliana involving malate dehydrogenase (mMDH) and l-2
      hydroxyglutarate dehydrogenase (l-2HGDH). We analyze the kinetic properties of
      both A. thaliana mMDH isoforms, and show that they produce l-2-hydroxyglutarate
      (l-2HG) from 2-ketoglutarate (2-KG) at low rates in side reactions. We identify
      A. thaliana l-2HGDH as a mitochondrial FAD-containing oxidase that converts l-2HG
      back to 2-KG. Using loss-of-function mutants, we show that the electrons produced
      in the l-2HGDH reaction are transferred to the mitochondrial electron transport
      chain through the electron transfer protein (ETF). Thus, plants possess the
      biochemical components of an l-2HG metabolic repair system identical to that
      found in mammals. While deficiencies in the metabolism of l-2HG result in fatal
      disorders in mammals, accumulation of l-2HG in plants does not adversely affect
      their development under a range of tested conditions. However, orthologs of l
      2HGDH are found in all examined genomes of viridiplantae, indicating that the
      repair reaction we identified makes an essential contribution to plant fitness in
      as yet unidentified conditions in the wild. 

PMID- 26203121
TI  - How accurate is the clinical assessment of acute dyspnoea and wheeze in children?

PMID- 26203122
TI  - What diseases are causally linked to vitamin D deficiency?
AB  - The classical clinical consequence of vitamin D deficiency is osteomalacia,
      presenting as rickets in children. This remains a common problem in parts of the
      Middle East and the Indian subcontinent, and occurs when serum 25-hydroxyvitamin
      D levels are <25 nmol/L. Osteomalacia remains the only problem that is
      unequivocally a consequence of vitamin D deficiency. Low levels of 25
      hydroxyvitamin D are observed in a wide range of conditions, but consistent trial
      evidence of amelioration of these conditions with vitamin D is lacking.
      Monotherapy with vitamin D has not been found to be effective in meta-analyses of
      trials assessing its effects on bone density, fractures or falls. At present,
      supplements should be advised for individuals at risk of having serum 25
      hydroxyvitamin D levels in the 25-40 nmol/L range, or below, with a view to
      prevention of osteomalacia. 

PMID- 26203123
TI  - Growth attenuation therapy: practice and perspectives of paediatric
      endocrinologists.

PMID- 26203124
TI  - Embracing risk.
AB  - I entered the science field because I imagined that scientists were society's
      "professional risk takers", that they like surfing out on the edge. I understood
      that a lot of science - perhaps even most science - has to be a solid exploration
      of partly understood phenomena. But any science that confronts a difficult
      problem has to start with risk. Most people are at least a bit suspicious of
      risk, and scientists such as myself are no exception. Recently, risk-taking has
      been under attack financially, but this Editorial is not about that. I am writing
      about the long view and the messages we send to our trainees. I am Senior
      Associate Dean of the graduate school at Mount Sinai and have had the privilege
      to discuss these issues with the next generation of scientists, for whom I care
      very deeply. Are we preparing you to embrace risk? 

PMID- 26203126
TI  - Correction for Woolgar et al., Fluid intelligence loss linked to restricted
      regions of damage within frontal and parietal cortex.

PMID- 26203125
TI  - RASopathies: unraveling mechanisms with animal models.
AB  - RASopathies are developmental disorders caused by germline mutations in the Ras
      MAPK pathway, and are characterized by a broad spectrum of functional and
      morphological abnormalities. The high incidence of these disorders (~1/1000
      births) motivates the development of systematic approaches for their efficient
      diagnosis and potential treatment. Recent advances in genome sequencing have
      greatly facilitated the genotyping and discovery of mutations in affected
      individuals, but establishing the causal relationships between molecules and
      disease phenotypes is non-trivial and presents both technical and conceptual
      challenges. Here, we discuss how these challenges could be addressed using
      genetically modified model organisms that have been instrumental in delineating
      the Ras-MAPK pathway and its roles during development. Focusing on studies in
      mice, zebrafish and Drosophila, we provide an up-to-date review of animal models
      of RASopathies at the molecular and functional level. We also discuss how
      increasingly sophisticated techniques of genetic engineering can be used to
      rigorously connect changes in specific components of the Ras-MAPK pathway with
      observed functional and morphological phenotypes. Establishing these connections
      is essential for advancing our understanding of RASopathies and for devising
      rational strategies for their management and treatment. 

PMID- 26203128
TI  - eComment. Alternative approaches to pyloric disruption after oesophagectomy:
      Stapled pyloroplasty versus dilatation and botox injection.

PMID- 26203127
TI  - High-resolution epitope mapping by HX MS reveals the pathogenic mechanism and a
      possible therapy for autoimmune TTP syndrome.
AB  - Acquired thrombotic thrombocytopenic purpura (TTP), a thrombotic disorder that is
      fatal in almost all cases if not treated promptly, is primarily caused by IgG
      type autoantibodies that inhibit the ability of the ADAMTS13 (a disintegrin and
      metalloproteinase with a thrombospondin type 1 motif, member 13) metalloprotease
      to cleave von Willebrand factor (VWF). Because the mechanism of autoantibody
      mediated inhibition of ADAMTS13 activity is not known, the only effective therapy
      so far is repeated whole-body plasma exchange. We used hydrogen-deuterium
      exchange mass spectrometry (HX MS) to determine the ADAMTS13 binding epitope for
      three representative human monoclonal autoantibodies, isolated from TTP patients
      by phage display as tethered single-chain fragments of the variable regions
      (scFvs). All three scFvs bind the same conformationally discontinuous epitopic
      region on five small solvent-exposed loops in the spacer domain of ADAMTS13. The
      same epitopic region is also bound by most polyclonal IgG autoantibodies in 23
      TTP patients that we tested. The ability of ADAMTS13 to proteolyze VWF is
      impaired by the binding of autoantibodies at the epitopic loops in the spacer
      domain, by the deletion of individual epitopic loops, and by some local
      mutations. Structural considerations and HX MS results rule out any disruptive
      structure change effect in the distant ADAMTS13 metalloprotease domain. Instead,
      it appears that the same ADAMTS13 loop segments that bind the autoantibodies are
      also responsible for correct binding to the VWF substrate. If so, the
      autoantibodies must prevent VWF proteolysis simply by physically blocking normal
      ADAMTS13 to VWF interaction. These results point to the mechanism for
      autoantibody action and an avenue for therapeutic intervention. 

PMID- 26203129
TI  - eComment. Atrial mitral regurgitation: a new paradigm to understand.

PMID- 26203130
TI  - eComment. Postoperative recurrence of spontaneous pneumothorax in younger
      patients: is it a matter of age, lung apex dystrophy or just a difficult air leak
      valuation through "a hole in a thorax" in video-assisted thoracic surgery?

PMID- 26203131
TI  - eComment. Evidence, experience or novelty for achieving the best outcome in
      surgery?

PMID- 26203132
TI  - eComment: Treating endoleak type 2 and disseminated intravascular coagulopathy
      after EVAR with tranexamic acid: the efficacy of killing two birds with one
      stone.

PMID- 26203133
TI  - Treatment solution by Careddu et al.

PMID- 26203134
TI  - A Role for the Locus Ceruleus in Reward Processing: Encoding Behavioral Energy
      Required for Goal-Directed Actions.

PMID- 26203136
TI  - Cognitive and Brain Profiles Associated with Current Neuroimaging Biomarkers of
      Preclinical Alzheimer's Disease.
AB  - Neuroimaging biomarkers, namely hippocampal volume loss, temporoparietal
      hypometabolism, and neocortical beta-amyloid (Abeta) deposition, are included in
      the recent research criteria for preclinical Alzheimer's disease (AD). However,
      how to use these biomarkers is still being debated, especially regarding their
      sequence. Our aim was to characterize the cognitive and brain profiles of elders
      classified as positive or negative for each biomarker to further our
      understanding of their use in the preclinical diagnosis of AD. Fifty-four
      cognitively normal individuals (age = 65.8 +/- 8.3 years) underwent
      neuropsychological tests (structural MRI, FDG-PET, and Florbetapir-PET) and were
      dichotomized into positive or negative independently for each neuroimaging
      biomarker. Demographic, neuropsychological, and neuroimaging data were compared
      between positive and negative subgroups. The MRI-positive subgroup had lower
      executive performances and mixed patterns of lower volume and metabolism in AD
      characteristic regions and in the prefrontal cortex. The FDG-positive subgroup
      showed only hypometabolism, predominantly in AD-sensitive areas extending to the
      whole neocortex, compared with the FDG-negative subgroup. The amyloid-positive
      subgroup was older and included more APOE epsilon4 carriers compared with the
      amyloid-negative subgroup. When considering MRI and/or FDG biomarkers together
      (i.e., the neurodegeneration-positive), there was a trend for an inverse
      relationship with Abeta deposition such that those with neurodegeneration tended
      to show less Abeta deposition and the reverse was true as well. Our findings
      suggest that: (1) MRI and FDG biomarkers provide complementary rather than
      redundant information and (2) relatively young cognitively normal elders tend to
      have either neurodegeneration or Abeta deposition, but not both, suggesting
      additive rather than sequential/causative links between AD neuroimaging
      biomarkers at this age. Significance statement: Neuroimaging biomarkers are
      included in the recent research criteria for preclinical Alzheimer's disease
      (AD). However, how to use these biomarkers is still being debated, especially
      regarding their sequence. Our findings suggest that MRI and FDG-PET biomarkers
      should be used in combination, offering an additive contribution instead of
      reflecting the same process of neurodegeneration. Moreover, the present study
      also challenges the hierarchical use of the neuroimaging biomarkers in
      preclinical AD because it suggests that the neurodegeneration observed in this
      population is not due to beta-amyloid deposition. Rather, our results suggest
      that beta-amyloid- and tau-related pathological processes may interact but not
      necessarily appear in a systematic sequence.

PMID- 26203135
TI  - Phosphoinositide 3-Kinase Gamma Contributes to Neuroinflammation in a Rat Model
      of Surgical Brain Injury.
AB  - Neuroinflammation plays an important role in the pathophysiology of surgical
      brain injury (SBI). Phosphoinositide 3-kinase gamma (PI3Kgamma), predominately
      expressed in immune and endothelial cells, activates multiple inflammatory
      responses. In the present study, we investigated the role of PI3Kgamma and
      PI3Kgamma-activated phosphodiesterase 3B (PDE3B) in neuroinflammation in a rat
      model of SBI. One hundred and fifty-two male Sprague Dawley rats (weight 280-350
      g) were subjected to a partial right frontal lobe corticotomy model of SBI. A
      PI3Kgamma pharmacological inhibitor (AS252424 or AS605240) was administered
      intraperitoneally. PI3Kgamma siRNA, human recombinant active-PI3Kgamma protein,
      or human recombinant active-PDE3B protein were administered
      intracerebroventricularly. Post-SBI assessments included neurobehavioral tests,
      brain water content, Western blot, and immunohistochemistry. Endogenous PI3Kgamma
      levels were increased within peri-resection brain tissues after SBI, accompanied
      by increased brain water content and neurological functional deficits. There was
      a trend toward increased endogenous PDE3B phosphorylation after SBI. The
      selective PI3Kgamma inhibitors AS252424 and AS605240 reduced brain water content
      surrounding corticotomy and improved neurological function after SBI. SBI
      increased and PI3Kgamma inhibitor decreased levels of myeloperoxidase, cluster of
      differentiation 3, mast cell degranulation, E-selectin, and IL-1 in peri
      resection brain tissues. Direct administration of human recombinant active
      PI3Kgamma protein and active-PDE3B protein countered the protective effect of
      AS252424. PI3Kgamma siRNA reduced PI3Kgamma levels, decreased brain water content
      within peri-resection brain tissues, and improved neurological function after
      SBI. Collectively, our findings suggest that PI3Kgamma contributed to
      neuroinflammation after SBI. The use of selective PI3Kgamma inhibitors may be a
      novel approach to ameliorating SBI via their anti-inflammation effects.
      Significance statement: Life-saving or elective neurosurgeries often involve
      unavoidable damages to neighboring, nondiseased brain tissues. Such surgical
      brain injury (SBI) is attributable exclusively to the neurosurgical procedure
      itself and may cause postoperative complications that exacerbate neurological
      function. Although the importance of this medical problem is fully acknowledged,
      intraoperative administration of adjunctive treatment such as steroids and
      mannitol to patients undergoing neurosurgery appear not to be efficient remedies
      for SBI. To date, the issue of perioperative neuroprotection specifically against
      SBI has not been well studied. Using a clinically relevant rat model of SBI, we
      are exploring a new neuroprotective strategy targeting phosphoinositide 3-kinase
      gamma (PI3Kgamma). PI3Kgamma activates multiple inflammatory responses. By
      attenuating neuroinflammation, selective PI3Kgamma inhibition would limit
      postoperative complications and benefit neurological outcomes.

PMID- 26203137
TI  - A Hierarchical Statistical Model of Natural Images Explains Tuning Properties in
      V2.
AB  - Previous theoretical and experimental studies have demonstrated tight
      relationships between natural image statistics and neural representations in V1.
      In particular, receptive field properties similar to simple and complex cells
      have been shown to be inferable from sparse coding of natural images. However,
      whether such a relationship exists in higher areas has not been clarified. To
      address this question for V2, we trained a sparse coding model that took as input
      the output of a fixed V1-like model, which was in its turn fed a large variety of
      natural image patches as input. After the training, the model exhibited response
      properties that were qualitatively and quantitatively compatible with three major
      neurophysiological results on macaque V2, as follows: (1) homogeneous and
      heterogeneous integration of local orientations (Anzai et al., 2007); (2) a wide
      range of angle selectivities with biased sensitivities to one component
      orientation (Ito and Komatsu, 2004); and (3) exclusive length and width
      suppression (Schmid et al., 2014). The reproducibility was stable across
      variations in several model parameters. Further, a formal classification of the
      internal representations of the model units offered detailed interpretations of
      the experimental data, emphasizing that a novel type of model cell that could
      detect a combination of local orientations converging toward a single spatial
      point (potentially related to corner-like features) played an important role in
      reproducing tuning properties compatible with V2. These results are consistent
      with the idea that V2 uses a sparse code of natural images. Significance
      statement: Sparse coding theory has successfully explained a number of receptive
      field properties in V1; but how about in V2? This question has recently become
      important since a variety of properties distinct from V1 have been discovered in
      V2, and thus a more integrative understanding is called for. Our study shows that
      a hierarchical sparse coding model of natural images explains three major
      response properties known in the macaque V2. We further provide a detailed
      analysis revealing the roles of different kinds of model cells in explaining the
      V2-specific properties. Our results thus offer the first sparse coding account
      for receptive field properties in V2 that has extensive biological relevance.

PMID- 26203138
TI  - Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as
      an Endogenous Suppressor of Repair after Spinal Cord Injury.
AB  - Axonal growth and neuronal rewiring facilitate functional recovery after spinal
      cord injury. Known interventions that promote neural repair remain limited in
      their functional efficacy. To understand genetic determinants of mammalian CNS
      axon regeneration, we completed an unbiased RNAi gene-silencing screen across
      most phosphatases in the genome. We identified one known and 17 previously
      unknown phosphatase suppressors of injury-induced CNS axon growth. Silencing
      Inpp5f (Sac2) leads to robust enhancement of axon regeneration and growth cone
      reformation. Results from cultured Inpp5f(-/-) neurons confirm lentiviral shRNA
      results from the screen. Consistent with the nonoverlapping substrate specificity
      between Inpp5f and PTEN, rapamycin does not block enhanced regeneration in
      Inpp5f(-/-) neurons, implicating mechanisms independent of the PI3K/AKT/mTOR
      pathway. Inpp5f(-/-) mice develop normally, but show enhanced anatomical and
      functional recovery after mid-thoracic dorsal hemisection injury. More
      serotonergic axons sprout and/or regenerate caudal to the lesion level, and
      greater numbers of corticospinal tract axons sprout rostral to the lesion.
      Functionally, Inpp5f-null mice exhibit enhanced recovery of motor functions in
      both open-field and rotarod tests. This study demonstrates the potential of an
      unbiased high-throughput functional screen to identify endogenous suppressors of
      CNS axon growth after injury, and reveals Inpp5f (Sac2) as a novel suppressor of
      CNS axon repair after spinal cord injury. Significance statement: The extent of
      axon regeneration is a critical determinant of neurological recovery from injury,
      and is extremely limited in the adult mammalian CNS. We describe an unbiased gene
      silencing screen that uncovered novel molecules suppressing axonal regeneration.
      Inpp5f (Sac2) gene deletion promoted recovery from spinal cord injury with no
      side effects. The mechanism of action is distinct from another lipid phosphatase
      implicated in regeneration, PTEN. This opens new pathways for investigation in
      spinal cord injury research. Furthermore the screening methodology can be applied
      on a genome wide scale to discovery the entire set of mammalian genes
      contributing to axonal regeneration.

PMID- 26203139
TI  - Hypothalamic Non-AgRP, Non-POMC GABAergic Neurons Are Required for Postweaning
      Feeding and NPY Hyperphagia.
AB  - The hypothalamus is critical for feeding and body weight regulation. Prevailing
      studies focus on hypothalamic neurons that are defined by selectively expressing
      transcription factors or neuropeptides including those expressing
      proopiomelanocortin (POMC) and agouti-related peptides (AgRP). The Cre expression
      driven by the pancreas-duodenum homeobox 1 promoter is abundant in several
      hypothalamic nuclei but not in AgRP or POMC neurons. Using this line, we
      generated mice with disruption of GABA release from a major subset of non-POMC,
      non-AgRP GABAergic neurons in the hypothalamus. These mice exhibited a reduction
      in postweaning feeding and growth, and disrupted hyperphagic responses to NPY.
      Disruption of GABA release severely diminished GABAergic input to the
      paraventricular hypothalamic nucleus (PVH). Furthermore, disruption of GABA-A
      receptor function in the PVH also reduced postweaning feeding and blunted NPY
      induced hyperphagia. Given the limited knowledge on postweaning feeding, our
      results are significant in identifying GABA release from a major subset of less
      appreciated hypothalamic neurons as a key mediator for postweaning feeding and
      NPY hyperphagia, and the PVH as one major downstream site that contributes
      significantly to the GABA action. Significance statement: Prevalent studies on
      feeding in the hypothalamus focus on well characterized, selective groups neurons
      [e.g., proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons], and
      as a result, the role of the majority of other hypothalamic neurons is largely
      neglected. Here, we demonstrated an important role for GABAergic projections from
      non-POMC non-AgRP neurons to the paraventricular hypothalamic nucleus in
      promoting postweaning (mainly nocturnal) feeding and mediating NPY-induced
      hyperphagia. Thus, these results signify an importance to study those yet to be
      defined hypothalamic neurons in the regulation of energy balance and reveal a
      neural basis for postweaning (nocturnal) feeding and NPY-mediated hyperphagia.

PMID- 26203140
TI  - A Specific Component of the Evoked Potential Mirrors Phasic Dopamine Neuron
      Activity during Conditioning.
AB  - Midbrain dopamine (DA) neurons are thought to be a critical node in the circuitry
      that mediates reward learning. DA neurons receive diverse inputs from regions
      distributed throughout the neuraxis from frontal neocortex to the mesencephalon.
      While a great deal is known about changes in the activity of individual DA
      neurons during learning, much less is known about the functional changes in the
      microcircuits in which DA neurons are embedded. Here we used local field
      potentials recorded from the midbrain of behaving mice to show that the midbrain
      evoked potential (mEP) faithfully reflects the temporal and spatial structure of
      the phasic response of midbrain neuron populations during conditioning. By
      comparing the mEP to simultaneously recorded single units, we identified specific
      components of the mEP that corresponded to phasic DA and non-DA responses to
      salient stimuli. The DA component of the mEP emerged with the acquisition of a
      conditioned stimulus, was extinguished following changes in reinforcement
      contingency, and could be inhibited by pharmacological manipulations that
      attenuate the phasic responses of DA neurons. In contrast to single-unit
      recordings, the mEP permitted relatively dense sampling of the midbrain circuit
      during conditioning and thus could be used to reveal the spatiotemporal structure
      of multiple intermingled midbrain circuits. Finally, the mEP response was stable
      for months and thus provides a new approach to study long-term changes in the
      organization of ventral midbrain microcircuits during learning. Significance
      statement: Neurons that synthesize and release the neurotransmitter dopamine play
      a critical role in voluntary reward-seeking behavior. Much of our insight into
      the function of dopamine neurons comes from recordings of individual cells in
      behaving animals; however, it is notoriously difficult to record from dopamine
      neurons due to their sparsity and depth, as well as the presence of intermingled
      non-dopaminergic neurons. Here we show that much of the information that can be
      learned from recordings of individual dopamine and non-dopamine neurons is also
      revealed by changes in specific components of the local field potential. This
      technique provides an accessible measurement that could prove critical to our
      burgeoning understanding of the molecular, functional, and anatomical diversity
      of neuron populations in the midbrain.

PMID- 26203141
TI  - Functional Oxygen Sensitivity of Astrocytes.
AB  - In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and
      neuronal function is rapidly impaired if oxygen supply is interrupted even for a
      short period of time. However, oxygen tension monitored by the peripheral
      (arterial) chemoreceptors is not sensitive to regional CNS differences in partial
      pressure of oxygen (PO2 ) that reflect variable levels of neuronal activity or
      local tissue hypoxia, pointing to the necessity of a functional brain oxygen
      sensor. This experimental animal (rats and mice) study shows that astrocytes, the
      most numerous brain glial cells, are sensitive to physiological changes in PO2 .
      Astrocytes respond to decreases in PO2 a few millimeters of mercury below normal
      brain oxygenation with elevations in intracellular calcium ([Ca(2+)]i). The
      hypoxia sensor of astrocytes resides in the mitochondria in which oxygen is
      consumed. Physiological decrease in PO2 inhibits astroglial mitochondrial
      respiration, leading to mitochondrial depolarization, production of free
      radicals, lipid peroxidation, activation of phospholipase C, IP3 receptors, and
      release of Ca(2+) from the intracellular stores. Hypoxia-induced [Ca(2+)]i
      increases in astrocytes trigger fusion of vesicular compartments containing ATP.
      Blockade of astrocytic signaling by overexpression of ATP-degrading enzymes or
      targeted astrocyte-specific expression of tetanus toxin light chain (to interfere
      with vesicular release mechanisms) within the brainstem respiratory rhythm
      generating circuits reveals the fundamental physiological role of astroglial
      oxygen sensitivity; in low-oxygen conditions (environmental hypoxia), this
      mechanism increases breathing activity even in the absence of peripheral
      chemoreceptor oxygen sensing. These results demonstrate that astrocytes are
      functionally specialized CNS oxygen sensors tuned for rapid detection of
      physiological changes in brain oxygenation. Significance statement: Most, if not
      all, animal cells possess mechanisms that allow them to detect decreases in
      oxygen availability leading to slow-timescale, adaptive changes in gene
      expression and cell physiology. To date, only two types of mammalian cells have
      been demonstrated to be specialized for rapid functional oxygen sensing: glomus
      cells of the carotid body (peripheral respiratory chemoreceptors) that stimulate
      breathing when oxygenation of the arterial blood decreases; and pulmonary
      arterial smooth muscle cells responsible for hypoxic pulmonary vasoconstriction
      to limit perfusion of poorly ventilated regions of the lungs. Results of the
      present study suggest that there is another specialized oxygen-sensitive cell
      type in the body, the astrocyte, that is tuned for rapid detection of
      physiological changes in brain oxygenation.

PMID- 26203143
TI  - Real-Time Strategy Video Game Experience and Visual Perceptual Learning.
AB  - Visual perceptual learning (VPL) is defined as long-term improvement in
      performance on a visual-perception task after visual experiences or training.
      Early studies have found that VPL is highly specific for the trained feature and
      location, suggesting that VPL is associated with changes in the early visual
      cortex. However, the generality of visual skills enhancement attributable to
      action video-game experience suggests that VPL can result from improvement in
      higher cognitive skills. If so, experience in real-time strategy (RTS) video-game
      play, which may heavily involve cognitive skills, may also facilitate VPL. To
      test this hypothesis, we compared VPL between RTS video-game players (VGPs) and
      non-VGPs (NVGPs) and elucidated underlying structural and functional neural
      mechanisms. Healthy young human subjects underwent six training sessions on a
      texture discrimination task. Diffusion-tensor and functional magnetic resonance
      imaging were performed before and after training. VGPs performed better than
      NVGPs in the early phase of training. White-matter connectivity between the right
      external capsule and visual cortex and neuronal activity in the right inferior
      frontal gyrus (IFG) and anterior cingulate cortex (ACC) were greater in VGPs than
      NVGPs and were significantly correlated with RTS video-game experience. In both
      VGPs and NVGPs, there was task-related neuronal activity in the right IFG, ACC,
      and striatum, which was strengthened after training. These results indicate that
      RTS video-game experience, associated with changes in higher-order cognitive
      functions and connectivity between visual and cognitive areas, facilitates VPL in
      early phases of training. The results support the hypothesis that VPL can occur
      without involvement of only visual areas. Significance statement: Although early
      studies found that visual perceptual learning (VPL) is associated with
      involvement of the visual cortex, generality of visual skills enhancement by
      action video-game experience suggests that higher-order cognition may be involved
      in VPL. If so, real-time strategy (RTS) video-game experience may facilitate VPL
      as a result of heavy involvement of cognitive skills. Here, we compared VPL
      between RTS video-game players (VGPs) and non-VGPs (NVGPs) and investigated the
      underlying neural mechanisms. VGPs showed better performance in the early phase
      of training on the texture discrimination task and greater level of neuronal
      activity in cognitive areas and structural connectivity between visual and
      cognitive areas than NVGPs. These results support the hypothesis that VPL can
      occur beyond the visual cortex.

PMID- 26203142
TI  - The Polarity Protein Pals1 Regulates Radial Sorting of Axons.
AB  - Myelin is essential for rapid and efficient action potential propagation in
      vertebrates. However, the molecular mechanisms regulating myelination remain
      incompletely characterized. For example, even before myelination begins in the
      PNS, Schwann cells must radially sort axons to form 1:1 associations. Schwann
      cells then ensheathe and wrap axons, and establish polarized, subcellular
      domains, including apical and basolateral domains, paranodes, and Schmidt
      Lanterman incisures. Intriguingly, polarity proteins, such as Pals1/Mpp5, are
      highly enriched in some of these domains, suggesting that they may regulate the
      polarity of Schwann cells and myelination. To test this, we generated mice with
      Schwann cells and oligodendrocytes that lack Pals1. During early development of
      the PNS, Pals1-deficient mice had impaired radial sorting of axons, delayed
      myelination, and reduced nerve conduction velocities. Although myelination and
      conduction velocities eventually recovered, polyaxonal myelination remained a
      prominent feature of adult Pals1-deficient nerves. Despite the enrichment of
      Pals1 at paranodes and incisures of control mice, nodes of Ranvier and paranodes
      were unaffected in Pals1-deficient mice, although we measured a significant
      increase in the number of incisures. As in other polarized cells, we found that
      Pals1 interacts with Par3 and loss of Pals1 reduced levels of Par3 in Schwann
      cells. In the CNS, loss of Pals1 affected neither myelination nor the
      establishment of polarized membrane domains. These results demonstrate that
      Schwann cells and oligodendrocytes use distinct mechanisms to control their
      polarity, and that radial sorting in the PNS is a key polarization event that
      requires Pals1. Significance statement: This paper reveals the role of the
      canonical polarity protein Pals1 in radial sorting of axons by Schwann cells.
      Radial sorting is essential for efficient and proper myelination and is disrupted
      in some types of congenital muscular dystrophy.

PMID- 26203144
TI  - Differential fMRI Activation Patterns to Noxious Heat and Tactile Stimuli in the
      Primate Spinal Cord.
AB  - Mesoscale local functional organizations of the primate spinal cord are largely
      unknown. Using high-resolution fMRI at 9.4 T, we identified distinct interhorn
      and intersegment fMRI activation patterns to tactile versus nociceptive heat
      stimulation of digits in lightly anesthetized monkeys. Within a spinal segment, 8
      Hz vibrotactile stimuli elicited predominantly fMRI activations in the middle
      part of ipsilateral dorsal horn (iDH), along with significantly weaker
      activations in ipsilateral (iVH) and contralateral (cVH) ventral horns. In
      contrast, nociceptive heat stimuli evoked widespread strong activations in the
      superficial part of iDH, as well as in iVH and contralateral dorsal (cDH) horns.
      As controls, only weak signal fluctuations were detected in the white matter. The
      iDH responded most strongly to both tactile and heat stimuli, whereas the cVH and
      cDH responded selectively to tactile versus nociceptive heat, respectively.
      Across spinal segments, iDH activations were detected in three consecutive
      segments in both tactile and heat conditions. Heat responses, however, were more
      extensive along the cord, with strong activations in iVH and cDH in two
      consecutive segments. Subsequent subunit B of cholera toxin tracer histology
      confirmed that the spinal segments showing fMRI activations indeed received
      afferent inputs from the stimulated digits. Comparisons of the fMRI signal time
      courses in early somatosensory area 3b and iDH revealed very similar hemodynamic
      stimulus-response functions. In summary, we identified with fMRI distinct
      segmental networks for the processing of tactile and nociceptive heat stimuli in
      the cervical spinal cord of nonhuman primates. Significance statement: This is
      the first fMRI demonstration of distinct intrasegmental and intersegmental
      nociceptive heat and touch processing circuits in the spinal cord of nonhuman
      primates. This study provides novel insights into the local functional
      organizations of the primate spinal cord for pain and touch, information that
      will be valuable for designing and optimizing therapeutic interventions for
      chronic pain management.

PMID- 26203145
TI  - The Neurodynamics of Affect in the Laboratory Predicts Persistence of Real-World
      Emotional Responses.
AB  - Failure to sustain positive affect over time is a hallmark of depression and
      other psychopathologies, but the mechanisms supporting the ability to sustain
      positive emotional responses are poorly understood. Here, we investigated the
      neural correlates associated with the persistence of positive affect in the real
      world by conducting two experiments in humans: an fMRI task of reward responses
      and an experience-sampling task measuring emotional responses to a reward
      obtained in the field. The magnitude of DLPFC engagement to rewards administered
      in the laboratory predicted reactivity of real-world positive emotion following a
      reward administered in the field. Sustained ventral striatum engagement in the
      laboratory positively predicted the duration of real-world positive emotional
      responses. These results suggest that common pathways are associated with the
      unfolding of neural processes over seconds and with the dynamics of emotions
      experienced over minutes. Examining such dynamics may facilitate a better
      understanding of the brain-behavior associations underlying emotion. Significance
      statement: How real-world emotion, experienced over seconds, minutes, and hours,
      is instantiated in the brain over the course of milliseconds and seconds is
      unknown. We combined a novel, real-world experience-sampling task with fMRI to
      examine how individual differences in real-world emotion, experienced over
      minutes and hours, is subserved by affective neurodynamics of brain activity over
      the course of seconds. When winning money in the real world, individuals
      sustaining positive emotion the longest were those with the most prolonged
      ventral striatal activity. These results suggest that common pathways are
      associated with the unfolding of neural processes over seconds and with the
      dynamics of emotions experienced over minutes. Examining such dynamics may
      facilitate a better understanding of the brain-behavior associations underlying
      emotion.

PMID- 26203146
TI  - SCYL2 Protects CA3 Pyramidal Neurons from Excitotoxicity during Functional
      Maturation of the Mouse Hippocampus.
AB  - Neuronal death caused by excessive excitatory signaling, excitotoxicity, plays a
      central role in neurodegenerative disorders. The mechanisms regulating this
      process, however, are still incompletely understood. Here we show that the coated
      vesicle-associated kinase SCYL2/CVAK104 plays a critical role for the normal
      functioning of the nervous system and for suppressing excitotoxicity in the
      developing hippocampus. Targeted disruption of Scyl2 in mice caused perinatal
      lethality in the vast majority of newborn mice and severe sensory-motor deficits
      in mice that survived to adulthood. Consistent with a neurogenic origin of these
      phenotypes, neuron-specific deletion of Scyl2 also caused perinatal lethality in
      the majority of newborn mice and severe neurological defects in adult mice. The
      neurological deficits in these mice were associated with the degeneration of
      several neuronal populations, most notably CA3 pyramidal neurons of the
      hippocampus, which we analyzed in more detail. The loss of CA3 neurons occurred
      during the functional maturation of the hippocampus and was the result of a BAX
      dependent apoptotic process. Excessive excitatory signaling was present at the
      onset of degeneration, and inhibition of excitatory signaling prevented the
      degeneration of CA3 neurons. Biochemical fractionation reveals that Scyl2
      deficient mice have an altered composition of excitatory receptors at synapses.
      Our findings demonstrate an essential role for SCYL2 in regulating neuronal
      function and survival and suggest a role for SCYL2 in regulating excitatory
      signaling in the developing brain. Significance statement: Here we examine the in
      vivo function of SCYL2, an evolutionarily conserved and ubiquitously expressed
      protein pseudokinase thought to regulate protein trafficking along the secretory
      pathway, and demonstrate its importance for the normal functioning of the nervous
      system and for suppressing excitatory signaling in the developing brain. Together
      with recent studies demonstrating a role of SCYL1 in preventing motor neuron
      degeneration, our findings clearly establish the SCY1-like family of protein
      pseudokinases as key regulators of neuronal function and survival.

PMID- 26203148
TI  - Multimodal Plasticity in Dorsal Striatum While Learning a Lateralized Navigation
      Task.
AB  - Growing evidence supports a critical role for the dorsal striatum in cognitive as
      well as motor control. Both lesions and in vivo recordings demonstrate a
      transition in the engaged dorsal striatal subregion, from dorsomedial to
      dorsolateral, as skill performance shifts from an attentive phase to a more
      automatic or habitual phase. What are the neural mechanisms supporting the
      cognitive and behavioral transitions in skill learning? To pursue this question,
      we used T-maze training during which rats transition from early, attentive
      (dorsomedial) to late habitual (dorsolateral) performance. Following early or
      late training, we performed the first direct comparison of bidirectional synaptic
      plasticity in striatal brain slices, and the first evaluation of striatal
      synaptic plasticity by hemisphere relative to a learned turn. Consequently, we
      find that long-term potentiation and long-term depression are independently
      modulated with learning rather than reciprocally linked as previously suggested.
      Our results establish that modulation of evoked synaptic plasticity with learning
      depends on striatal subregion, training stage, and hemisphere relative to the
      learned turn direction. Exclusive to the contralateral hemisphere, intrinsic
      excitability is enhanced in dorsomedial relative to dorsolateral medium spiny
      neurons early in training and population responses are dampened late in training.
      Neuronal reconstructions indicate dendritic remodeling after training, which may
      represent a novel form of pruning. In conclusion, we describe region- and
      hemisphere-specific changes in striatal synaptic, intrinsic, and morphological
      plasticity which correspond to T-maze learning stages, and which may play a role
      in the cognitive transition between attentive and habitual strategies.
      Significance statement: We investigated neural plasticity in dorsal striatum from
      rats that were briefly or extensively trained on a directional T-maze task. Our
      results demonstrate that both the extent of training and the direction a rat
      learns to turn control the location and type of change in synaptic plasticity. In
      addition, brief training produces changes in neuron excitability only within one
      striatal subregion, whereas all training produces widespread changes in dendritic
      morphology. Our results suggest that activity in dorsomedial striatum strengthens
      the rewarded turn after brief training, whereas activity in dorsolateral striatum
      suppresses unrewarded turns after extensive training. This study illuminates how
      plasticity mediates learning using a task recognized for transitioning subjects
      from attentive to automatic performance.

PMID- 26203147
TI  - Retinal and Tectal "Driver-Like" Inputs Converge in the Shell of the Mouse Dorsal
      Lateral Geniculate Nucleus.
AB  - The dorsal lateral geniculate nucleus (dLGN) is a model system for understanding
      thalamic organization and the classification of inputs as "drivers" or
      "modulators." Retinogeniculate terminals provide the primary excitatory drive for
      the relay of information to visual cortex (V1), while nonretinal inputs act in
      concert to modulate the gain of retinogeniculate signal transmission. How do
      inputs from the superior colliculus, a visuomotor structure, fit into this
      schema? Using a variety of anatomical, optogenetic, and in vitro physiological
      techniques in mice, we show that dLGN inputs from the superior colliculus
      (tectogeniculate) possess many of the ultrastructural and synaptic properties
      that define drivers. Tectogeniculate and retinogeniculate terminals converge to
      innervate one class of dLGN neurons within the dorsolateral shell, the primary
      terminal domain of direction-selective retinal ganglion cells. These dLGN neurons
      project to layer I of V1 to form synaptic contacts with dendrites of deeper-layer
      neurons. We suggest that tectogeniculate inputs act as "backseat drivers," which
      may alert shell neurons to movement commands generated by the superior
      colliculus. Significance statement: The conventional view of the dorsal lateral
      geniculate nucleus (dLGN) is that of a simple relay of visual information between
      the retina and cortex. Here we show that the dLGN receives strong excitatory
      input from both the retina and the superior colliculus. Thus, the dLGN is part of
      a specialized visual channel that provides cortex with convergent information
      about stimulus motion and eye movement and positioning.

PMID- 26203149
TI  - Induction of Interleukin-1beta by Human Immunodeficiency Virus-1 Viral Proteins
      Leads to Increased Levels of Neuronal Ferritin Heavy Chain, Synaptic Injury, and
      Deficits in Flexible Attention.
AB  - Synaptodendritic pruning and alterations in neurotransmission are the main
      underlying causes of HIV-associated neurocognitive disorders (HAND). Our studies
      in humans and nonhuman primates indicated that the protein ferritin heavy chain
      (FHC) is a critical player in neuronal changes and ensuing cognitive deficit
      observed in these patients. Here we focus on the effect of HIV proteins and
      inflammatory cytokines implicated in HAND on neuronal FHC levels, dendritic
      changes, and neurocognitive behavior. In two well characterized models of HAND
      (HIV transgenic and gp120-treated rats), we report reductions in spine density
      and dendritic branches in prefrontal cortex pyramidal neurons compared with age
      matched controls. FHC brain levels are elevated in these animals, which also show
      deficits in reversal learning. Moreover, IL-1beta, TNF-alpha, and HIV gp120
      upregulate FHC in rat cortical neurons. However, although the inflammatory
      cytokines directly altered neuronal FHC, gp120 only caused significant FHC
      upregulation in neuronal/glial cocultures, suggesting that glia are necessary for
      sustained elevation of neuronal FHC by the viral protein. Although the envelope
      protein induced secretion of IL-1beta and TNF-alpha in cocultures, TNF-alpha
      blockade did not affect gp120-mediated induction of FHC. Conversely, studies with
      an IL-1beta neutralizing antibody or specific IL-1 receptor antagonist revealed
      the primary involvement of IL-1beta in gp120-induced FHC changes. Furthermore,
      silencing of neuronal FHC abrogates the effect of gp120 on spines, and spine
      density correlates negatively with FHC levels or cognitive deficit. These results
      demonstrate that viral and host components of HIV infection increase brain
      expression of FHC, leading to cellular and functional changes, and point to IL
      1beta-targeted strategies for prevention of these alterations. Significance
      statement: This work demonstrates the key role of the cytokine IL-1beta in the
      regulation of a novel intracellular mediator [i.e., the protein ferritin heavy
      chain (FHC)] of HIV-induced dendritic damage and the resulting neurocognitive
      impairment. This is also the first study that systematically investigates
      dendritic damage in layer II/III prefrontal cortex neurons of two different non
      infectious models of HIV-associated neurocognitive disorders (HAND) and reveals a
      precise correlation of these structural changes with specific biochemical and
      functional alterations also reported in HIV patients. Overall, these data suggest
      that targeting the IL-1beta-dependent FHC increase may represent a valid strategy
      for neuroprotective adjuvant therapies in HAND.

PMID- 26203150
TI  - Neural Mechanisms for Acoustic Signal Detection under Strong Masking in an
      Insect.
AB  - Communication is fundamental for our understanding of behavior. In the acoustic
      modality, natural scenes for communication in humans and animals are often very
      noisy, decreasing the chances for signal detection and discrimination. We
      investigated the mechanisms enabling selective hearing under natural noisy
      conditions for auditory receptors and interneurons of an insect. In the studied
      katydid Mecopoda elongata species-specific calling songs (chirps) are strongly
      masked by signals of another species, both communicating in sympatry. The
      spectral properties of the two signals are similar and differ only in a small
      frequency band at 2 kHz present in the chirping species. Receptors sharply tuned
      to 2 kHz are completely unaffected by the masking signal of the other species,
      whereas receptors tuned to higher audio and ultrasonic frequencies show complete
      masking. Intracellular recordings of identified interneurons revealed two
      mechanisms providing response selectivity to the chirp. (1) Response selectivity
      is when several identified interneurons exhibit remarkably selective responses to
      the chirps, even at signal-to-noise ratios of -21 dB, since they are sharply
      tuned to 2 kHz. Their dendritic arborizations indicate selective connectivity
      with low-frequency receptors tuned to 2 kHz. (2) Novelty detection is when a
      second group of interneurons is broadly tuned but, because of strong stimulus
      specific adaptation to the masker spectrum and "novelty detection" to the 2 kHz
      band present only in the conspecific signal, these interneurons start to respond
      selectively to the chirp shortly after the onset of the continuous masker. Both
      mechanisms provide the sensory basis for hearing at unfavorable signal-to-noise
      ratios. Significance statement: Animal and human acoustic communication may
      suffer from the same "cocktail party problem," when communication happens in
      noisy social groups. We address solutions for this problem in a model system of
      two katydids, where one species produces an extremely noisy sound, yet the second
      species still detects its own song. Using intracellular recording techniques we
      identified two neural mechanisms underlying the surprising behavioral signal
      detection at the level of single identified interneurons. These neural mechanisms
      for signal detection are likely to be important for other sensory modalities as
      well, where noise in the communication channel creates similar problems. Also,
      they may be used for the development of algorithms for the filtering of specific
      signals in technical microphones or hearing aids.

PMID- 26203151
TI  - Rapid Visuomotor Corrective Responses during Transport of Hand-Held Objects
      Incorporate Novel Object Dynamics.
AB  - Numerous studies have shown that people are adept at learning novel object
      dynamics, linking applied force and motion, when performing reaching movements
      with hand-held objects. Here we investigated whether the control of rapid
      corrective arm responses, elicited in response to visual perturbations, has
      access to such newly acquired knowledge of object dynamics. Participants first
      learned to make reaching movements while grasping an object subjected to complex
      load forces that depended on the distance and angle of the hand from the start
      position. During a subsequent test phase, we examined grip and load force
      coordination during corrective arm movements elicited (within ~150 ms) in
      response to viewed sudden lateral shifts (1.5 cm) in target or object position.
      We hypothesized that, if knowledge of object dynamics is incorporated in the
      control of the corrective responses, grip force changes would anticipate the
      unusual load force changes associated with the corrective arm movements so as to
      support grasp stability. Indeed, we found that the participants generated grip
      force adjustments tightly coupled, both spatially and temporally, to the load
      force changes associated with the arm movement corrections. We submit that
      recently learned novel object dynamics are effectively integrated into
      sensorimotor control policies that support rapid visually driven arm corrective
      actions during transport of hand held objects. Significance statement: Previous
      studies have demonstrated that the motor system can learn, and make use of,
      internal models of object dynamics to generate feedforward motor commands.
      However, it is not known whether such internal models are incorporated into
      rapid, automatic arm movement corrections that compensate for errors that arise
      during movement. Here we demonstrate, for the first time, that internal models of
      novel object dynamics are integrated into rapid corrective arm movements made in
      response to visuomotor perturbations that, importantly, do not directly perturb
      the object.

PMID- 26203152
TI  - Mapping of Learned Odor-Induced Motivated Behaviors in the Mouse Olfactory
      Tubercle.
AB  - An odor induces food-seeking behaviors when humans and animals learned to
      associate the odor with food, whereas the same odor elicits aversive behaviors
      following odor-danger association learning. It is poorly understood how central
      olfactory circuits transform the learned odor cue information into appropriate
      motivated behaviors. The olfactory tubercle (OT) is an intriguing area of the
      olfactory cortex in that it contains medium spiny neurons as principal neurons
      and constitutes a part of the ventral striatum. The OT is therefore a candidate
      area for participation in odor-induced motivated behaviors. Here we mapped c-Fos
      activation of medium spiny neurons in different domains of the mouse OT following
      exposure to learned odor cues. Mice were trained to associate odor cues to a
      sugar reward or foot shock punishment to induce odor-guided approach behaviors or
      aversive behaviors. Regardless of odorant types, the anteromedial domain of the
      OT was activated by learned odor cues that induced approach behaviors, whereas
      the lateral domain was activated by learned odor cues that induced aversive
      behaviors. In each domain, a larger number of dopamine receptor D1 type neurons
      were activated than D2 type neurons. These results indicate that specific domains
      of the OT represent odor-induced distinct motivated behaviors rather than odor
      stimuli, and raise the possibility that neuronal type-specific activation in
      individual domains of the OT plays crucial roles in mediating the appropriate
      learned odor-induced motivated behaviors. Significance statement: Although
      animals learn to associate odor cues with various motivated behaviors, the
      underlying circuit mechanisms are poorly understood. The olfactory tubercle (OT),
      a subarea of the olfactory cortex, also constitutes the ventral striatum. Here,
      we trained mice to associate odors with either reward or punishment and mapped
      odor-induced c-Fos activation in the OT. Regardless of odorant types, the
      anteromedial domain was activated by approach behavior-inducing odors, whereas
      the lateral domain was activated by aversive behavior-inducing odors. In each
      domain, dopamine receptor D1 neurons were preferentially activated over D2
      neurons. The results indicate that specific OT domains represent odor-induced
      distinct motivated behaviors rather than odor types, and suggest the importance
      of neuronal type-specific activation in individual domains in mediating
      appropriate behaviors.

PMID- 26203153
TI  - Development of Adult-Generated Cell Connectivity with Excitatory and Inhibitory
      Cell Populations in the Hippocampus.
AB  - New neurons are generated continuously in the subgranular zone of the hippocampus
      and integrate into existing hippocampal circuits throughout adulthood. Although
      the addition of these new neurons may facilitate the formation of new memories,
      as they integrate, they provide additional excitatory drive to CA3 pyramidal
      neurons. During development, to maintain homeostasis, new neurons form
      preferential contacts with local inhibitory circuits. Using retroviral and
      transgenic approaches to label adult-generated granule cells, we first asked
      whether a comparable process occurs in the adult hippocampus in mice. Similar to
      development, we found that, during adulthood, new neurons form connections with
      inhibitory cells in the dentate gyrus, hilus, and CA3 regions as they integrate
      into hippocampal circuits. In particular, en passant bouton and filopodia
      connections with CA3 interneurons peak when adult-generated dentate granule cells
      (DGCs) are ~4 weeks of age, a time point when these cells are most excitable.
      Consistent with this, optical stimulation of 4-week-old (but not 6- or 8-week
      old) adult-generated DGCs strongly activated CA3 interneurons. Finally, we found
      that CA3 interneurons were activated robustly during learning and that their
      activity was strongly coupled with activity of 4-week-old (but not older) adult
      generated DGCs. These data indicate that, as adult-generated neurons integrate
      into hippocampal circuits, they transiently form strong anatomical, effective,
      and functional connections with local inhibitory circuits in CA3. Significance
      statement: New neurons are generated continuously in the subgranular zone of the
      hippocampus and integrate into existing hippocampal circuits throughout
      adulthood. Understanding how these cells integrate within well formed circuits
      will increase our knowledge about the basic principles governing circuit assembly
      in the adult hippocampus. This study uses a combined connectivity analysis
      (anatomical, functional, and effective) of the output connections of adult-born
      hippocampal cells to show that, as these cells integrate into hippocampal
      circuits, they transiently form strong connections with local inhibitory
      circuits. This transient increase of connectivity may represent an homeostatic
      process necessary to accommodate changes in the excitation/inhibition balance
      induced by the addition of these new excitatory cells to the preexisting
      excitatory hippocampal circuits.

PMID- 26203154
TI  - VPS35 in Dopamine Neurons Is Required for Endosome-to-Golgi Retrieval of Lamp2a,
      a Receptor of Chaperone-Mediated Autophagy That Is Critical for alpha-Synuclein
      Degradation and Prevention of Pathogenesis of Parkinson's Disease.
AB  - Vacuolar protein sorting-35 (VPS35) is essential for endosome-to-Golgi retrieval
      of membrane proteins. Mutations in the VPS35 gene have been identified in
      patients with autosomal dominant PD. However, it remains poorly understood if and
      how VPS35 deficiency or mutation contributes to PD pathogenesis. Here we provide
      evidence that links VPS35 deficiency to PD-like neuropathology. VPS35 was
      expressed in mouse dopamine (DA) neurons in substantia nigra pars compacta (SNpc)
      and STR (striatum)--regions that are PD vulnerable. VPS35-deficient mice
      exhibited PD-relevant deficits including accumulation of alpha-synuclein in SNpc
      DA neurons, loss of DA transmitter and DA neurons in SNpc and STR, and impairment
      of locomotor behavior. Further mechanical studies showed that VPS35-deficient DA
      neurons or DA neurons expressing PD-linked VPS35 mutant (D620N) had impaired
      endosome-to-Golgi retrieval of lysosome-associated membrane glycoprotein 2a
      (Lamp2a) and accelerated Lamp2a degradation. Expression of Lamp2a in VPS35
      deficient DA neurons reduced alpha-synuclein, supporting the view for Lamp2a as a
      receptor of chaperone-mediated autophagy to be critical for alpha-synuclein
      degradation. These results suggest that VPS35 deficiency or mutation promotes PD
      pathogenesis and reveals a crucial pathway, VPS35-Lamp2a-alpha-synuclein, to
      prevent PD pathogenesis. Significance statement: VPS35 is a key component of the
      retromer complex that is essential for endosome-to-Golgi retrieval of membrane
      proteins. Mutations in the VPS35 gene have been identified in patients with PD.
      However, if and how VPS35 deficiency or mutation contributes to PD pathogenesis
      remains unclear. We demonstrated that VPS35 deficiency or mutation (D620N) in
      mice leads to alpha-synuclein accumulation and aggregation in the substantia
      nigra, accompanied with DA neurodegeneration. VPS35-deficient DA neurons exhibit
      impaired endosome-to-Golgi retrieval of Lamp2a, which may contribute to the
      reduced alpha-synuclein degradation through chaperone-mediated autophagy. These
      results suggest that VPS35 deficiency or mutation promotes PD pathogenesis, and
      reveals a crucial pathway, VPS35-Lamp2a-alpha-synuclein, to prevent PD
      pathogenesis.

PMID- 26203156
TI  - Longitudinal follow-up and muscle MRI pattern of two siblings with polyglucosan
      body myopathy due to glycogenin-1 mutation.

PMID- 26203155
TI  - Orchestration of Neuronal Differentiation and Progenitor Pool Expansion in the
      Developing Cortex by SoxC Genes.
AB  - As the cerebral cortex forms, specialized molecular cascades direct the expansion
      of progenitor pools, the differentiation of neurons, or the maturation of
      discrete neuronal subtypes, together ensuring that the correct amounts and
      classes of neurons are generated. In several neural systems, the SoxC
      transcriptional regulators, particularly Sox11 and Sox4, have been characterized
      as functioning exclusively and redundantly in promoting neuronal differentiation.
      Using the mouse cerebral cortex as a model, Sox11 and Sox4 were examined in the
      formation of the most complex part of the mammalian brain. Anticipated
      prodifferentiation roles were observed. Distinct expression patterns and mutant
      phenotypes, however, reveal that Sox11 and Sox4 are not redundant in the cortex,
      but rather act in overlapping and discrete populations of neurons. In particular,
      Sox11 acts in early-born neurons; binding to its partner protein, Neurogenin1,
      leads to selective targeting and transactivation of a downstream gene, NeuroD1.
      In addition to neuronal expression, Sox4 was unexpectedly expressed in
      intermediate progenitor cells, the transit amplifying cell of the cerebral
      cortex. Sox4 mutant analyses reveal a requirement for Sox4 in IPC specification
      and maintenance. In intermediate progenitors, Sox4 partners with the proneural
      gene Neurogenin2 to activate Tbrain2 and then with Tbrain2 to maintain this cell
      fate. This work reveals an intricately structured molecular architecture for SoxC
      molecules, with Sox11 acting in a select set of cortical neurons and Sox4 playing
      an unanticipated role in designating secondary progenitors. 

PMID- 26203157
TI  - Multidimensional apathy in ALS: validation of the Dimensional Apathy Scale.
AB  - AIM: Apathy is a prominent symptom of amyotrophic lateral sclerosis (ALS), but
      measurement is confounded by physical disability. Furthermore, it has been
      traditionally measured as a unidimensional symptom despite research demonstrating
      a multifaceted construct. The new Dimensional Apathy Scale (DAS) has been
      specifically designed for patients with motor disability to measure 3
      neurologically based subtypes of apathy: Executive, Emotional and Initiation. We
      aimed to explore this behavioural symptom by examining the substructure of apathy
      in ALS and to determine the reliability and validity of the DAS in patients and
      their carers. METHOD: Patients and carers were recruited through the national
      Scottish Motor Neurone Disease Register and were asked to complete the DAS, the
      standardised Apathy Evaluation Scale, and the Geriatric Depression Scale-Short
      Form. 83 patients with ALS, 75 carers and 83 sex-matched, age-matched and
      education-matched controls participated. RESULTS: When compared with healthy
      controls, patients showed a significant increase in apathy on the Initiation
      subscale, and were significantly less apathetic on the Emotional subscale. Scores
      on the DAS patient and carer versions did not significantly differ. Internal
      consistency reliability, convergent and discriminant validity were found to be
      good for the DAS subscales. There was no association between the DAS and
      functional disability using the ALS Functional Rating Scale. CONCLUSIONS: Apathy
      in ALS is characterised by a specific profile of increased initiation apathy and
      reduced emotional apathy. The DAS is a reliable and valid measure for the
      assessment of multidimensional apathy in ALS.

PMID- 26203158
TI  - Diagnosis of dementias by high-field 1H MRS of cerebrospinal fluid.
AB  - OBJECTIVE: To test whether the information obtained from cerebrospinal fluid
      (CSF) and analysed with high-field proton ((1)H) MR spectroscopy (MRS) would help
      the diagnosis of most common forms of dementia. SETTING: A total of 31
      metabolites from CSF from 222 controls and patients suffering from various
      dementias (Alzheimer's disease (AD), vascular dementia, Lewy body disease (LBD)
      and frontotemporal dementia (FTD)) were quantified using (1)H MRS. MAIN OUTCOME
      MEASURE: Clinical diagnosis. RESULTS: AD was classified with an accuracy of
      85.5%. For a group of very early stage patients with AD, the result was
      significantly higher, 92.3%. Vascular dementia, LBD and FTD were all diagnosed
      with 100% accuracy in controls and from AD with an accuracy ranging between 85.5%
      and 93.4%. CONCLUSIONS: The results indicate that the composition of CSF contains
      enough information of the neurological state of a given patient with a given
      dementia to be diagnosed with extremely high accuracy. This approach might
      provide potentially a very powerful diagnostic tool to help the diagnostic
      process of dementias.

PMID- 26203159
TI  - Training monocytes by physical exercise: good practice for improving collateral
      artery development and postischemic outcomes.

PMID- 26203161
TI  - Correction.

PMID- 26203160
TI  - Adventitia and perivascular cells.

PMID- 26203162
TI  - Safety in numbers: more walkers and bicyclists, safer walking and bicycling.
AB  - OBJECTIVE: To examine the relationship between the numbers of people walking or
      bicycling and the frequency of collisions between motorists and walkers or
      bicyclists. The common wisdom holds that the number of collisions varies directly
      with the amount of walking and bicycling. However, three published analyses of
      collision rates at specific intersections found a non-linear relationship, such
      that collisions rates declined with increases in the numbers of people walking or
      bicycling. DATA: This paper uses five additional data sets (three population
      level and two time series) to compare the amount of walking or bicycling and the
      injuries incurring in collisions with motor vehicles. RESULTS: The likelihood
      that a given person walking or bicycling will be struck by a motorist varies
      inversely with the amount of walking or bicycling. This pattern is consistent
      across communities of varying size, from specific intersections to cities and
      countries, and across time periods. DISCUSSION: This result is unexpected. Since
      it is unlikely that the people walking and bicycling become more cautious if
      their numbers are larger, it indicates that the behavior of motorists controls
      the likelihood of collisions with people walking and bicycling. It appears that
      motorists adjust their behavior in the presence of people walking and bicycling.
      There is an urgent need for further exploration of the human factors controlling
      motorist behavior in the presence of people walking and bicycling. CONCLUSION: A
      motorist is less likely to collide with a person walking and bicycling if more
      people walk or bicycle. Policies that increase the numbers of people walking and
      bicycling appear to be an effective route to improving the safety of people
      walking and bicycling.

PMID- 26203163
TI  - Is it safe in numbers?

PMID- 26203164
TI  - SAVIR hosts dynamic conference.

PMID- 26203166
TI  - Hepatic insulin resistance and increased hepatic glucose production in mice
      lacking Fgf21.
AB  - Fibroblast growth factor 21 (FGF21) is an important regulator of hepatic glucose
      and lipid metabolism and represents a potential pharmacological agent for the
      treatment of type 2 diabetes and obesity. Mice fed a ketogenic diet (KD) develop
      hepatic insulin resistance in association with high levels of FGF21, suggesting a
      state of FGF21 resistance. To address the role of FGF21 in hepatic insulin
      resistance, we assessed insulin action in FGF21 whole-body knock-out (FGF21 KO)
      male mice and their littermate WT controls fed a KD. Here, we report that FGF21
      KO mice have hepatic insulin resistance and increased hepatic glucose production
      associated with an increase in plasma glucagon levels. FGF21 KO mice are also
      hypometabolic and display increased fat mass compared with their WT littermates.
      Taken together, these findings support a major role of FGF21 in regulating energy
      expenditure and hepatic glucose and lipid metabolism, and its potential role as a
      candidate in the treatment of diseases associated with insulin resistance. 

PMID- 26203165
TI  - RDGBalpha, a PtdIns-PtdOH transfer protein, regulates G-protein-coupled
      PtdIns(4,5)P2 signalling during Drosophila phototransduction.
AB  - Many membrane receptors activate phospholipase C (PLC) during signalling,
      triggering changes in the levels of several plasma membrane lipids including
      phosphatidylinositol (PtdIns), phosphatidic acid (PtdOH) and phosphatidylinositol
      4,5-bisphosphate [PtdIns(4,5)P2]. It is widely believed that exchange of lipids
      between the plasma membrane and endoplasmic reticulum (ER) is required to restore
      lipid homeostasis during PLC signalling, yet the mechanism remains unresolved.
      RDGBalpha (hereafter RDGB) is a multi-domain protein with a PtdIns transfer
      protein (PITP) domain (RDGB-PITPd). We find that, in vitro, the RDGB-PITPd binds
      and transfers both PtdOH and PtdIns. In Drosophila photoreceptors, which
      experience high rates of PLC activity, RDGB function is essential for
      phototransduction. We show that binding of PtdIns to RDGB-PITPd is essential for
      normal phototransduction; however, this property is insufficient to explain the
      in vivo function because another Drosophila PITP (encoded by vib) that also binds
      PtdIns cannot rescue the phenotypes of RDGB deletion. In RDGB mutants,
      PtdIns(4,5)P2 resynthesis at the plasma membrane following PLC activation is
      delayed and PtdOH levels elevate. Thus RDGB couples the turnover of both PtdIns
      and PtdOH, key lipid intermediates during G-protein-coupled PtdIns(4,5)P2
      turnover. 

PMID- 26203167
TI  - Postnatal overnutrition programs the thyroid hormone metabolism and function in
      adulthood.
AB  - Early overnutrition (EO) during lactation leads to obesity, leptin resistance and
      lower thyroid hormone (TH) levels during adulthood. To better understand the
      biological significance of this thyroid hypofunction, we studied the long-term
      effects of postnatal EO on both the function of hypothalamic-pituitary-thyroid
      (HPT) axis and the metabolism and action of TH. To induce EO, the litter size was
      reduced to three pups per litter (small litter (SL) group) on the third day of
      lactation. In the controls (normal litter group), litter size was adjusted to 10
      pups per litter. Rats were killed at PN180. TRH content and in vitro TSH were
      evaluated. Iodothyronine deiodinase (D1 and D2) activities were measured in
      different tissues. Mitochondrial alpha-glycerol-3-phosphate dehydrogenase (mGPD),
      uncoupling protein 1 (UCP1) and TH receptor (TRbeta1) were evaluated to assess TH
      action. The SL group presented lower TRH, intra-pituitary and released TSH
      levels, despite unchanged plasma TSH. They presented lower D1 activity in
      thyroid, muscle and white adipose tissue (WAT) and higher D2 activity in the
      hypothalamus, pituitary, brown adipose tissue (BAT) and WAT, which confirmed the
      hypothyroidism. UCP1 in BAT and TRbeta1 in WAT were decreased, which can
      contribute to a lower catabolic status. Despite the lower TH, the D2 activity in
      the thyroid, heart and testes was unchanged. Hepatic D1, mGPD and TRbeta1 were
      also unchanged in SL rats, suggesting that the TH conversion and action were
      preserved in the liver, even with lower TH. Thus, this model indicates that
      postnatal EO changes thyroid function in adult life in a tissue-specific way,
      which can help in the understanding of obesogenesis. 

PMID- 26203168
TI  - GeneCOST: a novel scoring-based prioritization framework for identifying disease
      causing genes.
AB  - Due to the big data produced by next-generation sequencing studies, there is an
      evident need for methods to extract the valuable information gathered from these
      experiments. In this work, we propose GeneCOST, a novel scoring-based method to
      evaluate every gene for their disease association. Without any prior filtering
      and any prior knowledge, we assign a disease likelihood score to each gene in
      correspondence with their variations. Then, we rank all genes based on frequency,
      conservation, pedigree and detailed variation information to find out the
      causative reason of the disease state. We demonstrate the usage of GeneCOST with
      public and real life Mendelian disease cases including recessive, dominant,
      compound heterozygous and sporadic models. As a result, we were able to identify
      causative reason behind the disease state in top rankings of our list, proving
      that this novel prioritization framework provides a powerful environment for the
      analysis in genetic disease studies alternative to filtering-based approaches.
      AVAILABILITY AND IMPLEMENTATION: GeneCOST software is freely available at
      www.igbam.bilgem.tubitak.gov.tr/en/softwares/genecost-en/index.html. CONTACT:
      buozer@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 26203169
TI  - Re-analysis of health and educational impacts of a school-based deworming
      programme in western Kenya: a pure replication.
AB  - BACKGROUND: Helminth (worm) infections cause morbidity among poor communities
      worldwide. An influential study conducted in Kenya in 1998-99 reported that a
      school-based drug-and-educational intervention had benefits regarding worm
      infections and school attendance. Effects were seen among children treated with
      deworming drugs, untreated children in intervention schools and children in
      nearby non-intervention schools. Combining these effects, the intervention was
      reported to increase school attendance by 7.5% in treated children. Effects on
      other outcomes (worm infections, anaemia, nutritional status and examination
      performance) were also investigated. METHODS: In this pure replication, we used
      data provided by the original authors to re-analyse the study according to their
      methods. We compared these results against those presented in the original paper.
      RESULTS: Although most results were reproduced as originally reported, we
      identified discrepancies of several types between the original findings and re
      analysis. For worm infections, re-analysis showed reductions similar to those
      originally reported. For anaemia prevalence, in contrast to the original
      findings, re-analysis found no evidence of benefit. For nutritional status, both
      original findings and re-analysis described modest evidence for a small
      improvement. For school attendance, re-analysis showed benefits similar to those
      originally found in intervention schools for both children who did and those who
      did not receive deworming drugs. However, after correction of coding errors,
      there was little evidence of an indirect effect on school attendance among
      children in schools close to intervention schools. Combining these effects gave a
      total increase in attendance of 3.9% among treated children, which was no longer
      statistically significant. As in the original results, re-analysis found no
      effect of the intervention on examination performance. CONCLUSIONS: Re-applying
      analytical approaches originally used, but correcting various errors, we found
      little evidence for some previously-reported indirect effects of a deworming
      intervention. Effects on worm infections, nutritional status, examination
      performance and school attendance on children in intervention schools were
      largely unchanged.

PMID- 26203170
TI  - Commentary: Deworming externalities and schooling impacts in Kenya: a comment on
      Aiken et al. (2015) and Davey et al. (2015).

PMID- 26203171
TI  - Re-analysis of health and educational impacts of a school-based deworming
      programme in western Kenya: a statistical replication of a cluster quasi
      randomized stepped-wedge trial.
AB  - INTRODUCTION: Helminth (worm) infections cause morbidity among poor communities
      worldwide. An influential study conducted in Kenya in 1998-99 reported that a
      school-based drug-and-educational intervention had benefits for worm infections
      and school attendance. METHODS: In this statistical replication, we re-analysed
      data from this cluster quasi-randomized stepped-wedge trial, specifying two co
      primary outcomes: school attendance and examination performance. We estimated
      intention-to-treat effects using year-stratified cluster-summary analysis and
      observation-level random-effects regression, and combined both years with a
      random-effects model accounting for year. The participants were not blinded to
      allocation status, and other interventions were concurrently conducted in a sub
      set of schools. A protocol guiding outcome data collection was not available.
      RESULTS: Quasi-randomization resulted in three similar groups of 25 schools.
      There was a substantial amount of missing data. In year-stratified cluster
      summary analysis, there was no clear evidence for improvement in either school
      attendance or examination performance. In year-stratified regression models,
      there was some evidence of improvement in school attendance [adjusted odds ratios
      (aOR): year 1: 1.48, 95% confidence interval (CI) 0.88-2.52, P = 0.147; year 2:
      1.23, 95% CI 1.01-1.51, P = 0.044], but not examination performance (adjusted
      differences: year 1: -0.135, 95% CI -0.323-0.054, P = 0.161; year 2: -0.017, 95%
      CI -0.201-0.166, P = 0.854). When both years were combined, there was strong
      evidence of an effect on attendance (aOR 1.82, 95% CI 1.74-1.91, P < 0.001), but
      not examination performance (adjusted difference -0.121, 95% CI -0.293-0.052, P =
      0.169). CONCLUSIONS: The evidence supporting an improvement in school attendance
      differed by analysis method. This, and various other important limitations of the
      data, caution against over-interpretation of the results. We find that the study
      provides some evidence, but with high risk of bias, that a school-based drug
      treatment and health-education intervention improved school attendance and no
      evidence of effect on examination performance.

PMID- 26203172
TI  - Commentary: Replication of influential trial helps international policy.

PMID- 26203173
TI  - Authors' Response to: Deworming externalities and school impacts in Kenya.

PMID- 26203174
TI  - Progestin and AdipoQ Receptor 7, Progesterone Membrane Receptor Component 1
      (PGRMC1), and PGRMC2 and Their Role in Regulating Progesterone's Ability to
      Suppress Human Granulosa/Luteal Cells from Entering into the Cell Cycle.
AB  - The present studies were designed to determine the role of progesterone receptor
      membrane component 1 (PGRMC1), PGRMC2, progestin and adipoQ receptor 7 (PAQR7),
      and progesterone receptor (PGR) in mediating the antimitotic action of
      progesterone (P4) in human granulosa/luteal cells. For these studies
      granulosa/luteal cells of 10 women undergoing controlled ovarian hyperstimulation
      were isolated, maintained in culture, and depleted of PGRMC1, PGRMC2, PAQR7, or
      PGR by siRNA treatment. The rate of entry into the cell cycle was assessed using
      the FUCCI cell cycle sensor to determine the percentage of cells in the G1/S
      stage of the cell cycle. PGRMC1, PGRMC2, PAQR7, and PGR mRNA levels were assessed
      by real-time PCR and their interactions monitored by in situ proximity ligation
      assays (PLAs). These studies revealed that PGRMC1, PGRMC2, PAQR7, and PGR were
      expressed by granulosa/luteal cells from all patients, with PGRMC1 mRNA being
      most abundant, followed by PAQR7, PGRMC2, and PGR. However, their mRNA levels
      showed considerable patient variation. P4's ability to suppress entry into the
      cell cycle was dependent on PGRMC1, PGRMC2, and PAQR7 but not PGR. Moreover, PLAs
      indicated that PGRMC1, PGRMC2, and PAQR7 formed a complex within the cytoplasm.
      Based on these studies, it is proposed that these three P4 mediators form a
      complex within the cytoplasm that is required for P4's action. Moreover, P4's
      ability to regulate human follicle development may be dependent in part on the
      expression levels of each of these P4 mediators. 

PMID- 26203176
TI  - A Role of sFlt-1 in Oxidative Stress and Apoptosis in Human and Mouse Pre
      Eclamptic Trophoblasts.
AB  - Pre-eclampsia (PE) is a hypertensive disorder that occurs during pregnancy, and
      is a multifactorial disease. The antiangiogenic factor, soluble fms-like tyrosine
      kinase 1 (sFlt-1), has been reported to be important in the pathogenesis of PE,
      but the mechanism of its involvement remains unknown. To test the effects of sFlt
      1 on pregnancy, we injected pregnant mice with exogenous mouse sFlt-1. After 18
      days of gestation, higher blood pressure, proteinuria, and histological
      differences were observed compared with controls. Mitochondrial swelling inside
      the trophoblast cells in the placenta of sFlt-1-treated pregnant mice was
      observed by electron microscopy, which suggested a role of sFlt-1 in oxidative
      stress in trophoblasts in PE. Furthermore, apoptosis markers were upregulated in
      sFlt-1-treated mice. In conclusion, sFlt-1 appears to play a role in oxidative
      stress, which promotes apoptosis of trophoblasts. This may be an important
      mechanism in the development of PE. 

PMID- 26203175
TI  - A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic
      Phenotypes of Polycystic Ovary Syndrome in Female Mice.
AB  - Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly
      to lack of PCOS animal models fully recapitulating this complex disorder.
      Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase
      inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent
      in other models. Given the advantages of using genetic and transgenic mouse
      models, we investigated whether LET produces a similar PCOS phenotype in mice.
      Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in
      increased serum testosterone and normal diestrus levels of estradiol, similar to
      the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in
      PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea
      versus controls. Most LET females were acyclic, and all were infertile. LET
      females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary.
      In contrast, serum FSH and Fshb were significantly reduced in LET females,
      demonstrating differential effects on gonadotropins, as in PCOS. Within the
      ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In
      the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but
      lower progesterone receptor mRNA levels. LET females also gained more weight than
      controls, had increased abdominal adiposity and adipocyte size, elevated adipose
      inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic
      phenotype in PCOS women. This is the first report of a LET paradigm in mice that
      recapitulates both reproductive and metabolic PCOS phenotypes and will be useful
      to genetically probe the PCOS condition. 

PMID- 26203177
TI  - LH-Induced Steroidogenesis in the Mouse Ovary, but Not Testis, Requires Matrix
      Metalloproteinase 2- and 9-Mediated Cleavage of Upregulated EGF Receptor Ligands.
AB  - Oocyte maturation and cumulus cell expansion depend on luteinizing hormone (LH)
      mediated upregulation of membrane-bound epidermal growth factor (EGF)-like
      ligands, including amphiregulin, epiregulin, and betacellulin. These ligands then
      transactivate the EGF receptor (EGFR) after release by matrix metalloproteinases
      (MMPs). However, direct measurement of released EGF-like ligands or MMPs from
      granulosa cells has not been formally evaluated, nor has direct identification of
      responsible MMPs. Here we address these issues by analyzing LH-induced
      steroidogenesis, which is also MMP and EGFR dependent, in freshly isolated mouse
      primary granulosa cells. We demonstrate a correlation between amphiregulin and
      epiregulin mRNA induction and steroid production in LH-treated granulosa cells as
      well as in ovaries of human chorionic gonadotropin-treated mice. In contrast, LH
      does not alter Mmp1, Mmp2, Mmp3, Mmp8, Mmp9, or Adam17 mRNA expression. We
      demonstrate that, in primary mouse granulosa cells, LH triggers release of
      soluble amphiregulin that correlates with steroid production, both of which are
      blocked by MMP2/9 inhibition, confirming that MMP2/9 likely regulates LH-induced
      amphiregulin release and downstream processes. Notably, LH does not alter
      secretion of MMP2/9 from primary granulosa cells, nor does it modulate MMP
      activity. These findings indicate that, in the ovary, LH dictates EGFR-mediated
      processes not by regulating MMPs, but instead by increasing EGF-like ligand
      availability. In contrast, LH stimulation of primary mouse Leydig cells does not
      induce EGF-like ligand expression or require MMP2/9 for steroidogenesis,
      confirming marked differences in LH receptor-induced processes in the testes. Our
      results suggest that MMP inhibition may be a means of attenuating excess ovarian
      steroid production in diseases like polycystic ovary syndrome. 

PMID- 26203178
TI  - Changes in Ca2+ Signaling and Nitric Oxide Output by Human Umbilical Vein
      Endothelium in Diabetic and Gestational Diabetic Pregnancies.
AB  - Diabetes (DM) complicates 3%-10% of pregnancies, resulting in significant
      maternal and neonatal morbidity and mortality. DM pregnancies are also associated
      with vascular dysfunction, including blunted nitric oxide (NO) output, but it
      remains unclear why. Herein we examine changes in endothelial NO production and
      its relationship to Ca(2+) signaling in endothelial cells of intact umbilical
      veins from control versus gestational diabetic (GDM) or preexisting diabetic
      subjects. We have previously reported that endothelial cells of intact vessels
      show sustained Ca(2+) bursting in response to ATP, and these bursts drive
      prolonged NO production. Herein we show that in both GDM and DM pregnancies, the
      incidence of Ca(2+) bursts remains similar, but there is a reduction in overall
      sustained phase Ca(2+) mobilization and a reduction in NO output. Further studies
      show damage has occurred at the level of NOS3 protein itself. Since exposure to
      DM serum is known to impair normal human umbilical vein endothelial cell (HUVEC)
      function, we further studied the ability of HUVEC to signal through Ca(2+) after
      they were isolated from DM and GDM subjects and maintained in culture for several
      days. These HUVEC showed differences in the rate of Ca(2+) bursting, with DM >
      GDM = control HUVEC. Both GDM- and DM-derived HUVEC showed smaller Ca(2+) bursts
      that were less capable of NOS3 activation compared to control HUVEC. We conclude
      that HUVEC from DM and GDM subjects are reprogrammed such that the Ca(2+)
      bursting peak shape and duration are permanently impaired. This may explain why
      ROS therapy alone is not effective in DM and GDM subjects. 

PMID- 26203180
TI  - Efavirenz and the CNS: what we already know and questions that need to be
      answered.
AB  - The NNRTI efavirenz has long been one of the most frequently employed
      antiretroviral drugs in the multidrug regimens used to treat HIV infection, in
      accordance with its well-demonstrated antiretroviral efficacy and favourable
      pharmacokinetics. However, growing concern about its adverse effects has
      sometimes led to efavirenz being replaced by other drugs in the initial treatment
      selection or to switching of therapy to efavirenz-free regimens in experienced
      patients. Neurological and neuropsychiatric reactions are the manifestations most
      frequently experienced by efavirenz-treated patients and range from transitory
      effects, such as nightmares, dizziness, insomnia, nervousness and lack of
      concentration, to more severe symptoms including depression, suicidal ideation or
      even psychosis. In addition, efavirenz has recently been associated with
      mild/moderate neurocognitive impairment, which is of specific relevance given
      that half of the patients receiving ART eventually suffer some form of HIV
      associated neurocognitive disorder. The mechanisms responsible for efavirenz
      induced neurotoxicity are unclear, although growing evidence points to
      disturbances in brain mitochondrial function and bioenergetics. This review
      offers a comprehensive overview of the current evidence on the interaction that
      efavirenz displays with the CNS, including the penetration and concentration of
      the drug in the brain. We discuss the prevalence, types and specificities of its
      side effects and recently uncovered cellular mechanisms that may be involved in
      their development. 

PMID- 26203179
TI  - A Screen for Genomic Disorders of Infertility Identifies MAST2 Duplications
      Associated with Nonobstructive Azoospermia in Humans.
AB  - Since the cytogenetic identification of azoospermia factor regions 40 years ago,
      the Y chromosome has dominated research on the genetics of male infertility. We
      hypothesized that hotspots of structural rearrangement, which are dispersed
      across the genome, may mediate rare, recurrent copy number variations (CNVs),
      leading to severe infertility. We tested this hypothesis by contrasting patterns
      of rare CNVs in 970 Han Chinese men with idiopathic nonobstructive azoospermia
      and 1661 ethnicity-matched controls. Our results strongly support our previous
      claim that sperm production is modulated by genetic variation across the entire
      genome. The X chromosome in particular was enriched for loci modulating
      spermatogenesis--rare X-linked deletions larger than 100 kb were twice as common
      in patients compared with controls (odds ratio [OR] = 2.05, P = 0.01). At
      rearrangement hotspots across the genome, we observed a 2.4-fold enrichment of
      singleton CNVs in patients (P < 0.02), and we identified 117 testis genes, such
      as SYCE1, contained within 47 hotspots that may plausibly mediate genomic
      disorders of fertility. In our discovery sample we observed 3 case-specific
      duplications of the autosomal gene MAST2, and in a replication phase we found
      another 11 duplications in 1457 patients and 1 duplication in 1590 controls (P <
      5 * 10(-5), combined data). With a large, polygenic genetic basis, new ways of
      establishing the pathogenicity of rare, large-effect mutations will be needed to
      fully reap the benefit of genome data in the management of azoospermia.

PMID- 26203181
TI  - Adaptation to vancomycin pressure of multiresistant Staphylococcus capitis NRCS-A
      involved in neonatal sepsis.
AB  - OBJECTIVES: The Staphylococcus capitis clone NRCS-A has recently been described
      as a frequent cause of late-onset sepsis (LOS) in pre-term neonates worldwide.
      Representatives of this clone exhibit non-susceptibility to vancomycin, the first
      line agent used in LOS. Cases of prolonged S. capitis LOS despite vancomycin
      treatment have been reported. We investigated whether NRCS-A strains exhibit
      faster adaptation to vancomycin pressure as compared with other staphylococci.
      METHODS: Strains of S. capitis NRCS-A, S. capitis non-NRCS-A and Staphylococcus
      epidermidis (n = 2 each, all with vancomycin MICs <=2 mg/L) and the prototype
      vancomycin-heteroresistant Staphylococcus aureus Mu3 were subcultured daily for
      15 days with 0.25-32 mg/L vancomycin. Regression coefficients of daily log2 MICs
      on time were used to estimate the kinetics of resistance development. Changes in
      bacterial cell-wall thickness were measured by transmission electron microscopy.
      To assess the stability of resistance and the emergence of cross-resistance,
      vancomycin, teicoplanin, daptomycin and linezolid MICs were measured before and
      after vancomycin treatment, as well as after nine additional subcultures without
      antibiotics. RESULTS: All strains developed a stable resistance to vancomycin,
      but this occurred significantly faster in S. capitis NRCS-A than in S. capitis
      non-NRCS-A (P < 0.001) and other species (P < 0.0001). Vancomycin resistance in
      S. capitis NRCS-A was associated with significant cell-wall thickening and an
      increase in MICs of daptomycin and teicoplanin, but not linezolid. CONCLUSIONS:
      S. capitis NRCS-A rapidly adapts to vancomycin pressure as compared with
      potential niche competitors, a feature that might contribute to its success in
      neonatal ICUs where vancomycin is widely prescribed.

PMID- 26203182
TI  - Pulmonary drug delivery: a review on nanocarriers for antibacterial chemotherapy.
AB  - As the WHO stated, lower respiratory infections are the third leading cause of
      death. In addition, it is remarkable that antimicrobial resistance represents a
      huge threat. Thus, new therapeutic weapons are required. Among the possible
      alternatives, antibiotic encapsulation in nanoparticles has gained much attention
      in terms of improved tolerability, activity and ability to combat the resistance
      mechanisms of bacteria. In this regard, this review article focuses on the latest
      nanocarrier approaches for inhalatory therapy of antibiotics. First, the
      technology related to lung disposition will be reviewed. Then, nanocarrier
      systems will be introduced and the challenges required to perform adequate
      pulmonary deposition analysed. In the following part, drug delivery systems
      (DDSs) on the market or in clinical trials are described and, finally, new
      approaches of nanoparticles that have reached pre-clinical stage are enumerated.
      Altogether, this review aims at gathering together the novel nanosystems for anti
      infectious therapy, underlining the potential of DDSs to improve and optimize
      currently available antibiotic therapies in the context of lung infections. 

PMID- 26203183
TI  - Fitness of artemisinin-resistant Plasmodium falciparum in vitro.
AB  - OBJECTIVES: Drug resistance confers a fitness advantage to parasites exposed to
      frequent drug pressure, yet these mutations also may incur a fitness cost. We
      assessed fitness advantages and costs of artemisinin resistance in Plasmodium
      falciparum in vitro to understand how drug resistance will spread and evolve in a
      competitive environment. METHODS: Genotyping of SNPs, drug susceptibility assays
      and copy number determination were used to assess the impact of artemisinin
      resistance on parasite fitness. An artemisinin-resistant clone (C9) selected in
      vitro from an isogenic parental clone (D6) was used to conduct competitive growth
      studies to assess fitness of artemisinin resistance. The resistant and
      susceptible clones were mixed or grown alone in the presence and absence of drug
      pressure (dihydroartemisinin or pyrimethamine) to quantify the rate at which
      artemisinin resistance was gained or lost. RESULTS: We experimentally demonstrate
      for the first time that artemisinin resistance provides a fitness advantage that
      is selected for with infrequent exposure to drug, but is lost in the absence of
      exposure to artemisinin drugs. The best correlations with artemisinin resistance
      were decreased in vitro drug susceptibility to artemisinin derivatives, increased
      copy number of Pf3D7_1030100 and an SNP in Pf3D7_0307600. An SNP conferring an
      E208K mutation in the kelch gene (Pf3D7_1343700) was not associated with
      resistance. Furthermore, we observed second-cycle ring-stage dormancy induced by
      pyrimethamine, suggesting that dormancy is a fitness trait that provides an
      advantage for survival from antimalarial drug stress. CONCLUSIONS: Artemisinin
      resistant P. falciparum have a fitness advantage to survive and predominate in
      the population even in the face of infrequent exposure to artemisinin drugs.

PMID- 26203184
TI  - Outcomes of pulmonary MDR-TB: impacts of fluoroquinolone resistance and linezolid
      treatment.
AB  - OBJECTIVES: Fluoroquinolones (FQs) are the most important second-line drugs for
      MDR-TB treatment. Therapeutic options for FQ-resistant (FQ-R) MDR/XDR-TB are very
      limited. The purpose of the present study was to determine treatment outcomes and
      risk factors associated with unfavourable outcomes of MDR/XDR-TB, focusing on the
      impacts of FQ-R status and linezolid treatment. METHODS: This was a retrospective
      cohort study of 337 MDR-TB patients, including 144 (42.7%) FQ-R MDR/XDR-TB cases.
      Treatment outcomes were evaluated according to WHO 2013 recommendations. RESULTS:
      Later-generation FQs such as levofloxacin or moxifloxacin were given to 331
      (98.2%) patients. Overall, favourable outcomes were achieved in 272 (80.7%)
      patients. FQ-R second-line injectable drug-susceptible MDR [adjusted OR (aOR)
      4.299, 95% CI 1.239-14.916, P = 0.015] and XDR status (aOR 6.294, 95% CI 1.204
      32.909, P = 0.024) were independently associated with unfavourable outcomes.
      However, FQ-susceptible (FQ-S) second-line injectable drug-resistant MDR status
      was not associated with unfavourable outcomes (aOR 1.814, 95% CI 0.314-10.485, P
      = 0.999). Favourable treatment outcomes were more frequent in FQ-R MDR/XDR-TB
      patients who received linezolid (82.8%) compared with those who did not receive
      linezolid (58.1%, P = 0.002). When FQ-R MDR/XDR-TB treatment without linezolid
      was used as a reference, the addition of linezolid was associated with favourable
      outcomes (aOR 4.081, 95% CI 1.237-13.460, P = 0.017), comparable to those for FQ
      S MDR-TB (aOR 4.341, 95% CI 1.470-12.822, P = 0.005). CONCLUSIONS: Later
      generation FQs could improve treatment outcomes of patients with MDR-TB.
      Linezolid should be considered for inclusion in FQ-R MDR/XDR-TB treatment
      regimens.

PMID- 26203185
TI  - Fenofibric Acid Can Cause False-Positive Urine Methylenedioxymethamphetamine
      Immunoassay Results.
AB  - We present a false-positive result of ecstasy (3,4-methylenedioxy-NN
      methylamphetamine) screening due to the therapeutic use of fenofibrate, an
      antihyperlipidemic drug. Our hypothesis was that the main metabolite of
      fenofibrate, fenofibric acid, was responsible for this cross-reactivity on a
      DRI((r)) Ecstasy Assay, using a cut-off of 500 ng/mL. We estimated that the
      addition of 225 ug/mL pure fenofibric acid to blank urine would be sufficient to
      result in a positive DRI((r)) Ecstasy Assay. The results obtained on the urine
      samples analyses of the patient show that the DRI((r)) Ecstasy Assay resulted
      negative 2 days after discontinuing fenofibrate treatment, when the urine
      fenofibric acid concentration corrected by creatinine and determinated by gas
      chromatography-mass spectrometry was 20.3 ug/mg creatinine. The cross-reactivity
      data for fenofibric acid would seem to indicate that there was insufficient
      concentration of measured compound to account for the positive immunochemical
      results for ecstasy. This apparent discrepancy can be explained in several ways,
      one of them is that the beta-glucuronidase-resistent fenofibric acid isomers are
      responsible. This process could explain the low recovery of free fenofibric acid
      when we use the developed method for its quantification in urine samples.
      Positive results on immunoassay screening must be considered presumptive until
      confirmation with another method based on a different principle, preferably gas
      chromatography-mass spectrometry or liquid chromatography-mass spectrometry. 

PMID- 26203186
TI  - Signal Transduction by BvgS Sensor Kinase: BINDING OF MODULATOR NICOTINATE
      AFFECTS THE CONFORMATION AND DYNAMICS OF THE ENTIRE PERIPLASMIC MOIETY.
AB  - The two-component sensory transduction system BvgAS controls the virulence
      regulon of the whooping-cough agent Bordetella pertussis. The periplasmic moiety
      of the homodimeric sensor kinase BvgS is composed of four bilobed Venus flytrap
      (VFT) perception domains followed by alpha helices that extend into the
      cytoplasmic membrane. In the virulent phase, the default state of B. pertussis,
      the cytoplasmic enzymatic moiety of BvgS acts as kinase by autophosphorylating
      and transferring the phosphoryl group to the response regulator BvgA. Under
      laboratory conditions, BvgS shifts to phosphatase activity in response to
      modulators, notably nicotinate ions. Here we characterized the effects of
      nicotinate and related modulators on the BvgS periplasmic moiety by using site
      directed mutagenesis and in silico and biophysical approaches. Modulators bind
      with low affinity to BvgS in the VFT2 cavity. Electron paramagnetic resonance
      shows that their binding globally affects the conformation and dynamics of the
      periplasmic moiety. Specific amino acid substitutions designed to slacken
      interactions within and between the VFT lobes prevent BvgS from responding to
      nicotinate, showing that BvgS shifts from kinase to phosphatase activity in
      response to this modulator via a tense transition state that involves a large
      periplasmic structural block. We propose that this transition enables the
      transmembrane helices to adopt a distinct conformation that sets the cytoplasmic
      enzymatic moiety in the phosphatase mode. The bona fide, in vivo VFT ligands that
      remain to be identified are likely to trigger similar effects on the
      transmembrane and cytoplasmic moieties. This mechanism may be relevant to the
      other VFT-containing sensor kinases homologous to BvgS. 

PMID- 26203187
TI  - A Mutation in Transmembrane Domain 7 (TM7) of Excitatory Amino Acid Transporters
      Disrupts the Substrate-dependent Gating of the Intrinsic Anion Conductance and
      Drives the Channel into a Constitutively Open State.
AB  - In the mammalian central nervous system, excitatory amino acid transporters
      (EAATs) are responsible for the clearance of glutamate after synaptic release.
      This energetically demanding activity is crucial for precise neuronal
      communication and for maintaining extracellular glutamate concentrations below
      neurotoxic levels. In addition to their ability to recapture glutamate from the
      extracellular space, EAATs exhibit a sodium- and glutamate-gated anion
      conductance. Here we show that substitution of a conserved positively charged
      residue (Arg-388, hEAAT1) in transmembrane domain 7 with a negatively charged
      amino acid eliminates the ability of glutamate to further activate the anion
      conductance. When expressed in oocytes, R388D or R388E mutants show large anion
      currents that display no further increase in amplitude after application of
      saturating concentrations of Na(+) and glutamate. They also show a substantially
      reduced transport activity. The mutant transporters appear to exist
      preferentially in a sodium- and glutamate-independent constitutive open channel
      state that rarely transitions to complete the transport cycle. In addition, the
      accessibility of cytoplasmic residues to membrane-permeant modifying reagents
      supports the idea that this substrate-independent open state correlates with an
      intermediate outward facing conformation of the transporter. Our data provide
      additional insights into the mechanism by which substrates gate the anion
      conductance in EAATs and suggest that in EAAT1, Arg-388 is a critical element for
      the structural coupling between the substrate translocation and the gating
      mechanisms of the EAAT-associated anion channel. 

PMID- 26203188
TI  - Proteomic and Metabolic Analyses of S49 Lymphoma Cells Reveal Novel Regulation of
      Mitochondria by cAMP and Protein Kinase A.
AB  - Cyclic AMP (cAMP), acting via protein kinase A (PKA), regulates many cellular
      responses, but the role of mitochondria in such responses is poorly understood.
      To define such roles, we used quantitative proteomic analysis of mitochondria
      enriched fractions and performed functional and morphologic studies of wild-type
      (WT) and kin(-) (PKA-null) murine S49 lymphoma cells. Basally, 75 proteins
      significantly differed in abundance between WT and kin(-) S49 cells. WT, but not
      kin(-), S49 cells incubated with the cAMP analog 8-(4-chlorophenylthio)adenosine
      cAMP (CPT-cAMP) for 16 h have (a) increased expression of mitochondria-related
      genes and proteins, including ones in pathways of branched-chain amino acid and
      fatty acid metabolism and (b) increased maximal capacity of respiration on
      branched-chain keto acids and fatty acids. CPT-cAMP also regulates the cellular
      rate of ATP-utilization, as the rates of both ATP-linked respiration and proton
      efflux are decreased in WT but not kin(-) cells. CPT-cAMP protected WT S49 cells
      from glucose or glutamine deprivation, In contrast, CPT-cAMP did not protect kin(
      ) cells or WT cells treated with the PKA inhibitor H89 from glutamine
      deprivation. Under basal conditions, the mitochondrial structure of WT and kin(-)
      S49 cells is similar. Treatment with CPT-cAMP produced apoptotic changes (i.e.
      decreased mitochondrial density and size and loss of cristae) in WT, but not kin(
      ) cells. Together, these findings show that cAMP acts via PKA to regulate
      multiple aspects of mitochondrial function and structure. Mitochondrial
      perturbation thus likely contributes to cAMP/PKA-mediated cellular responses. 

PMID- 26203189
TI  - The Transmembrane Domains of beta and IX Subunits Mediate the Localization of the
      Platelet Glycoprotein Ib-IX Complex to the Glycosphingolipid-enriched Membrane
      Domain.
AB  - We have previously reported that the structural elements of the GP Ib-IX complex
      required for its localization to glycosphingolipid-enriched membranes (GEMs)
      reside in the Ibbeta and IX subunits. To identify them, we generated a series of
      cell lines expressing mutant GP Ibbeta and GP IX where 1) the cytoplasmic tails
      (CTs) of either or both GP Ibbeta and IX are truncated, and 2) the transmembrane
      domains (TMDs) of GP Ibbeta and GP IX were swapped with the TMD of a non-GEMs
      associating molecule, human transferrin receptor. Sucrose density fractionation
      analysis showed that the removal of either or both of the CTs from GP Ibbeta and
      GP IX does not alter GP Ibalpha-GEMs association when compared with the wild
      type. In contrast, swapping of the TMDs of either GP Ibbeta or GP IX with that of
      transferrin receptor results in a significant loss (~ 50%) of GP Ibalpha from the
      low density GEMs fractions, with the largest effect seen in the dual TMD-replaced
      cells (> 80% loss) when compared with the wild type cells (100% of GP Ibalpha
      present in the GEMs fractions). Under high shear flow, the TMD-swapped cells
      adhere poorly to a von Willebrand factor-immobilized surface to a much lesser
      extent than the previously reported disulfide linkage dysfunctional GP Ibalpha
      expressing cells. Thus, our data demonstrate that the bundle of GP Ibbeta and GP
      IX TMDs instead of their individual CTs is the structural element that mediates
      the beta/IX complex localization to the membrane GEMs, which through the
      alpha/beta disulfide linkage brings GP Ibalpha into the GEMs.

PMID- 26203190
TI  - The protein BpsB is a poly-beta-1,6-N-acetyl-D-glucosamine deacetylase required
      for biofilm formation in Bordetella bronchiseptica.
AB  - Bordetella pertussis and Bordetella bronchiseptica are the causative agents of
      whooping cough in humans and a variety of respiratory diseases in animals,
      respectively. Bordetella species produce an exopolysaccharide, known as the
      Bordetella polysaccharide (Bps), which is encoded by the bpsABCD operon. Bps is
      required for Bordetella biofilm formation, colonization of the respiratory tract,
      and confers protection from complement-mediated killing. In this report, we have
      investigated the role of BpsB in the biosynthesis of Bps and biofilm formation by
      B. bronchiseptica. BpsB is a two-domain protein that localizes to the periplasm
      and outer membrane. BpsB displays metal- and length-dependent deacetylation on
      poly-beta-1,6-N-acetyl-d-glucosamine (PNAG) oligomers, supporting previous
      immunogenic data that suggests Bps is a PNAG polymer. BpsB can use a variety of
      divalent metal cations for deacetylase activity and showed highest activity in
      the presence of Ni(2+) and Co(2+). The structure of the BpsB deacetylase domain
      is similar to the PNAG deacetylases PgaB and IcaB and contains the same
      circularly permuted family four carbohydrate esterase motifs. Unlike PgaB from
      Escherichia coli, BpsB is not required for polymer export and has unique
      structural differences that allow the N-terminal deacetylase domain to be active
      when purified in isolation from the C-terminal domain. Our enzymatic
      characterizations highlight the importance of conserved active site residues in
      PNAG deacetylation and demonstrate that the C-terminal domain is required for
      maximal deacetylation of longer PNAG oligomers. Furthermore, we show that BpsB is
      critical for the formation and complex architecture of B. bronchiseptica
      biofilms. 

PMID- 26203191
TI  - The miR-200 family and its targets regulate type II cell differentiation in human
      fetal lung.
AB  - Type II cell differentiation and expression of the major surfactant protein, SP
      A, in mid-gestation human fetal lung (HFL) are induced by cAMP and inhibited by
      TGF-beta. cAMP induction of SP-A promoter activity is mediated by increased
      phosphorylation and DNA binding of thyroid transcription factor-1 (TTF-1/Nkx2.1),
      a master regulator of lung development. To further define mechanisms for
      developmental induction of surfactant synthesis in HFL, herein, we investigated
      the potential roles of microRNAs (miRNAs, miRs). To identify and characterize
      differentially regulated miRNAs in mid-gestation HFL explants during type II
      pneumocyte differentiation in culture, we performed miRNA microarray of RNA from
      epithelial cells isolated from mid-gestation HFL explants before and after
      culture with or without Bt2cAMP. Interestingly, the miR-200 family was
      significantly up-regulated during type II cell differentiation; miR-200 induction
      was inversely correlated with expression of known targets, transcription factors
      ZEB1/2 and TGF-beta2. miR-200 antagonists inhibited TTF-1 and surfactant proteins
      and up-regulated TGF-beta2 and ZEB1 expression in type II cells. Overexpression
      of ZEB1 in type II cells decreased DNA binding of endogenous TTF-1, blocked cAMP
      stimulation of surfactant proteins, and inhibited miR-200 expression, whereas
      cAMP markedly inhibited ZEB1/2 and TGF-beta. Importantly, overexpression of ZEB1
      or miR-200 antagonists in HFL type II cells also inhibited LPCAT1 and ABCA3,
      enzymes involved in surfactant phospholipid synthesis and trafficking, and
      blocked lamellar body biogenesis. Our findings suggest that the miR-200 family
      and ZEB1, which exist in a double-negative feedback loop regulated by TGF-beta,
      serve important roles in the developmental regulation of type II cell
      differentiation and function in HFL. 

PMID- 26203192
TI  - Hepatitis C Virus Particle Assembly Involves Phosphorylation of NS5A by the c-Abl
      Tyrosine Kinase.
AB  - Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is thought to regulate
      the replication of viral RNA and the assembly of virus particles in a
      serine/threonine phosphorylation-dependent manner. However, the host kinases that
      phosphorylate NS5A have not been fully identified. Here, we show that HCV
      particle assembly involves the phosphorylation of NS5A by the c-Abl tyrosine
      kinase. Pharmacological inhibition or knockdown of c-Abl reduces the production
      of infectious HCV (J6/JFH1) particles in Huh-7.5 cells without markedly affecting
      viral RNA translation and replication. NS5A is tyrosine-phosphorylated in HCV
      infected cells, and this phosphorylation is also reduced by the knockdown of c
      Abl. Mutational analysis reveals that NS5A tyrosine phosphorylation is dependent,
      at least in part, on Tyr(330) (Tyr(2306) in polyprotein numbering). Mutation of
      this residue to phenylalanine reduces the production of infectious HCV particles
      but does not affect the replication of the JFH1 subgenomic replicon. These
      findings suggest that c-Abl promotes HCV particle assembly by phosphorylating
      NS5A at Tyr(330). 

PMID- 26203193
TI  - Finerenone Impedes Aldosterone-dependent Nuclear Import of the Mineralocorticoid
      Receptor and Prevents Genomic Recruitment of Steroid Receptor Coactivator-1.
AB  - Aldosterone regulates sodium homeostasis by activating the mineralocorticoid
      receptor (MR), a member of the nuclear receptor superfamily. Hyperaldosteronism
      leads todeleterious effects on the kidney, blood vessels, and heart. Although
      steroidal antagonists such as spironolactone and eplerenone are clinically useful
      for the treatment of cardiovascular diseases, they are associated with several
      side effects. Finerenone, a novel nonsteroidal MR antagonist, is presently being
      evaluated in two clinical phase IIb trials. Here, we characterized the molecular
      mechanisms of action of finerenone and spironolactone at several key steps of the
      MR signaling pathway. Molecular modeling and mutagenesis approaches allowed
      identification of Ser-810 and Ala-773 as key residues for the high MR selectivity
      of finerenone. Moreover, we showed that, in contrast to spironolactone, which
      activates the S810L mutant MR responsible for a severe form of early onset
      hypertension, finerenone displays strict antagonistic properties. Aldosterone
      dependent phosphorylation and degradation of MR are inhibited by both finerenone
      and spironolactone. However, automated quantification of MR subcellular
      distribution demonstrated that finerenone delays aldosterone-induced nuclear
      accumulation of MR more efficiently than spironolactone. Finally, chromatin
      immunoprecipitation assays revealed that, as opposed to spironolactone,
      finerenone inhibits MR, steroid receptor coactivator-1, and RNA polymerase II
      binding at the regulatory sequence of the SCNN1A gene and also remarkably reduces
      basal MR and steroid receptor coactivator-1 recruitment, unraveling a specific
      and unrecognized inactivating mechanism on MR signaling. Overall, our data
      demonstrate that the highly potent and selective MR antagonist finerenone
      specifically impairs several critical steps of the MR signaling pathway and
      therefore represents a promising new generation MR antagonist. 

PMID- 26203194
TI  - Structural Aspects of N-Glycosylations and the C-terminal Region in Human
      Glypican-1.
AB  - Glypicans are multifunctional cell surface proteoglycans involved in several
      important cellular signaling pathways. Glypican-1 (Gpc1) is the predominant
      heparan sulfate proteoglycan in the developing and adult human brain. The two N
      linked glycans and the C-terminal domain that attach the core protein to the cell
      membrane are not resolved in the Gpc1 crystal structure. Therefore, we have
      studied Gpc1 using crystallography, small angle x-ray scattering, and
      chromatographic approaches to elucidate the composition, structure, and function
      of the N-glycans and the C terminus and also the topology of Gpc1 with respect to
      the membrane. The C terminus is shown to be highly flexible in solution, but it
      orients the core protein transverse to the membrane, directing a surface
      evolutionarily conserved in Gpc1 orthologs toward the membrane, where it may
      interact with signaling molecules and/or membrane receptors on the cell surface,
      or even the enzymes involved in heparan sulfate substitution in the Golgi
      apparatus. Furthermore, the N-glycans are shown to extend the protein stability
      and lifetime by protection against proteolysis and aggregation. 

PMID- 26203196
TI  - Toward Localized In Vivo Biomarker Concentration Measurements.
AB  - We know a great deal about the biochemistry of cells because they can be isolated
      and studied. The biochemistry of the much more complex in vivo environment is
      more difficult to study because the only ways to quantitate concentrations is to
      sacrifice the animal or biopsy the tissue. Either method disrupts the environment
      profoundly and neither method allows longitudinal studies on the same individual.
      Methods of measuring chemical concentrations in vivo are very valuable
      alternatives to sacrificing groups of animals. We are developing microscopic
      magnetic nanoparticle (mNP) probes to measure the concentration of a selected
      molecule in vivo. The mNPs are targeted to bind the selected molecule and the
      resulting reduction in rotational freedom can be quantified remotely using
      magnetic spectroscopy. The mNPs must be contained in micrometer sized porous
      shells to keep them from migrating and to protect them from clearance by the
      immune system. There are two key issues in the development of the probes. First,
      we demonstrate the ability to measure concentrations in the porous walled
      alginate probes both in phosphate buffered saline and in blood, which is an
      excellent surrogate for the complex and challenging in vivo environment. Second,
      sensitivity is critical because it allows microscopic probes to measure very
      small concentrations very far away. We report sensitivity measurements on
      recently introduced technology that has allowed us to improve the sensitivity by
      two orders of magnitude, a factor of 200 so far.

PMID- 26203197
TI  - Older Parent - Child Relationships in Six Developed Nations: Comparisons at the
      Intersection of Affection and Conflict.
AB  - Intergenerational solidarity and ambivalence paradigms suggest that emotional
      relationships between generations consist of both positive and negative
      sentiments. We applied latent class analysis to measures of affection and
      conflict in 2,698 older parent - child relationships in 6 developed nations:
      England, Germany, Israel, Norway, Spain, and the United States (Southern
      California). The best fitting model consisted of 4 latent classes distributed
      differently across nations but with a cross-nationally invariant measurement
      structure. After controlling for demographics, health, coresidence, contact, and
      support, the following classes were overrepresented in corresponding nations:
      amicable (England), detached (Germany and Spain), disharmonious (United States),
      ambivalent (Israel). We discuss policy and cultural differences across societies
      that may explain why the prevalence of particular emotional types varied by
      nation.

PMID- 26203195
TI  - Nucleolar GTP-binding Protein-1 (NGP-1) Promotes G1 to S Phase Transition by
      Activating Cyclin-dependent Kinase Inhibitor p21 Cip1/Waf1.
AB  - Nucleolar GTP-binding protein (NGP-1) is overexpressed in various cancers and
      proliferating cells, but the functional significance remains unknown. In this
      study, we show that NGP-1 promotes G1 to S phase transition of cells by enhancing
      CDK inhibitor p21(Cip-1/Waf1) expression through p53. In addition, our results
      suggest that activation of the cyclin D1-CDK4 complex by NGP-1 via maintaining
      the stoichiometry between cyclin D1-CDK4 complex and p21 resulted in
      hyperphosphorylation of retinoblastoma protein at serine 780 (p-RB(Ser-780))
      followed by the up-regulation of E2F1 target genes required to promote G1 to S
      phase transition. Furthermore, our data suggest that ribosomal protein RPL23A
      interacts with NGP-1 and abolishes NGP-1-induced p53 activity by enhancing Mdm2
      mediated p53 polyubiquitination. Finally, reduction of p-RB(Ser-780) levels and
      E2F1 target gene expression upon ectopic expression of RPL23a resulted in arrest
      at the G1 phase of the cell cycle. Collectively, this investigation provides
      evidence that NGP-1 promotes cell cycle progression through the activation of the
      p53/p21(Cip-1/Waf1) pathway. 

PMID- 26203198
TI  - Computational study of peptide permeation through membrane: Searching for hidden
      slow variables.
AB  - Atomically detailed molecular dynamics trajectories in conjunction with
      Milestoning are used to analyze the different contributions of coarse variables
      to the permeation process of a small peptide (N-acetyl-L-tryptophanamide, NATA)
      through a 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membrane. The peptide
      reverses its overall orientation as it permeates through the biological bilayer.
      The large change in orientation is investigated explicitly but is shown to impact
      the free energy landscape and permeation time only moderately. Nevertheless, a
      significant difference in permeation properties of the two halves of the membrane
      suggests the presence of other hidden slow variables. We speculate, based on
      calculation of the potential of mean force, that a conformational transition of
      NATA makes significant contribution to these differences. Other candidates for
      hidden slow variables may include water permeation and collective motions of
      phospholipids.

PMID- 26203199
TI  - Are Children "Normal"?
AB  - We examine Becker's (1960) contention that children are "normal." For the cross
      section of non-Hispanic white married couples in the U.S., we show that when we
      restrict comparisons to similarly-educated women living in similarly-expensive
      locations, completed fertility is positively correlated with the husband's
      income. The empirical evidence is consistent with children being "normal." In an
      effort to show causal effects, we analyze the localized impact on fertility of
      the mid-1970s increase in world energy prices - an exogenous shock that
      substantially increased men's incomes in the Appalachian coal-mining region.
      Empirical evidence for that population indicates that fertility increases in
      men's income.

PMID- 26203200
TI  - Do Religious Children Care More and Provide More Care for Older Parents? A Study
      of Filial Norms and Behaviors across Five Nations.

PMID- 26203201
TI  - Model-based Reconstruction of Objects with Inexactly Known Components.
AB  - Because tomographic reconstructions are ill-conditioned, algorithms that
      incorporate additional knowledge about the imaging volume generally have improved
      image quality. This is particularly true when measurements are noisy or have
      missing data. This paper presents a general reconstruction framework for
      including attenuation contributions from objects known to be in the field-of
      view. Components such as surgical devices and tools may be modeled explicitly as
      part of the attenuating volume but are inexactly known with respect to their
      locations poses, and possible deformations. The proposed reconstruction
      framework, referred to as Known-Component Reconstruction (KCR), is based on this
      novel parameterization of the object, a likelihood-based objective function, and
      alternating optimizations between registration and image parameters to jointly
      estimate the both the underlying attenuation and unknown registrations. A
      deformable KCR (dKCR) approach is introduced that adopts a control point-based
      warping operator to accommodate shape mismatches between the component model and
      the physical component, thereby allowing for a more general class of inexactly
      known components. The KCR and dKCR approaches are applied to low-dose cone-beam
      CT data with spine fixation hardware present in the imaging volume. Such data is
      particularly challenging due to photon starvation effects in projection data
      behind the metallic components. The proposed algorithms are compared with
      traditional filtered-backprojection and penalized-likelihood reconstructions and
      found to provide substantially improved image quality. Whereas traditional
      approaches exhibit significant artifacts that complicate detection of breaches or
      fractures near metal, the KCR framework tends to provide good visualization of
      anatomy right up to the boundary of surgical devices.

PMID- 26203202
TI  - The Language of Driving: Advantages and Applications of Symbolic Data Reduction
      for Analysis of Naturalistic Driving Data.
AB  - Recent advances in onboard vehicle data recording devices have created an
      abundance of naturalistic driving data. The amount of data exceeds the resources
      available for analysis; this situation forces researchers to focus on analyses of
      critical events and to use simple heuristics to identify those events. Critical
      event analysis eliminates the context that can be critical in understanding
      driver behavior and can reduce the generalizability of the analysis. This work
      introduced a method of naturalistic driving data analysis that would allow
      researchers to examine entire data sets by reducing the sets by more than 90%.
      The method utilized a symbolic data reduction algorithm, symbolic aggregate
      approximation (SAX), which reduced time series data to a string of letters. SAX
      can be applied to any continuous measurement, and SAX output can be reintegrated
      into a data set to preserve categorical information. This work explored the
      application of SAX to speed and acceleration data from a naturalistic driving
      data set and demonstrated SAX's integration with other methods that could begin
      to tame the complexity of naturalistic data.

PMID- 26203203
TI  - Diabetes Has Gotten Pretty Darn Complicated.

PMID- 26203204
TI  - Adherence to Guidelines for Hepatitis B, Pneumococcal, and Influenza Vaccination
      in Patients With Diabetes.
AB  - IN BRIEF This single-center, cross-sectional study was designed to assess
      adherence to national guidelines for the immunization of patients with diabetes
      and to evaluate predictors of vaccination with the hepatitis B, influenza, and 23
      valent pneumococcal polysaccharide vaccines. In patients considered to be at
      increased risk for infection and infectious disease complications because of
      their history of diabetes, extensive nonadherence to immunization recommendations
      for all three vaccines was found. Nonadherence to the 2011 Advisory Committee on
      Immunization Practices' recommendation for hepatitis B vaccination was
      ubiquitous. Allocation of health care resources to increase vaccine coverage
      should remain a priority, with a focus on spreading awareness of the hepatitis B
      vaccine recommendation for people with diabetes. 

PMID- 26203205
TI  - Insulin Therapy: A Personal Approach.
AB  - IN BRIEF Insulin therapy is challenging for providers as well as for patients.
      This article describes a set of principles underlying appropriate insulin
      treatment and a detailed discussion of how to use them. 

PMID- 26203206
TI  - Dynamics, Impact, and Feasibility of Self-Monitoring of Blood Glucose in the
      Rural, Resource-Constrained Setting of Western Kenya.

PMID- 26203207
TI  - Results of the Epidemiology of Diabetes Interventions and Complications Trial.

PMID- 26203208
TI  - Supraventricular Tachycardia With Underlying Atrial Flutter in a Diabetic
      Ketoacidosis Patient.

PMID- 26203209
TI  - Diabetes 1.5: Ketone-Prone Diabetes.

PMID- 26203210
TI  - Screening for Gestational Diabetes Mellitus: Are Guidelines From High-Income
      Settings Applicable to Poorer Countries?

PMID- 26203211
TI  - Experimental study on CO and CO2 emissions from spontaneous heating of coals at
      varying temperatures and O2 concentrations.
AB  - Laboratory experiments were conducted to investigate carbon monoxide (CO) and
      carbon dioxide (CO2) emissions from spontaneous heating of three U.S. coal
      samples in an isothermal oven at temperatures between 50 and 110  degrees C. The
      oxygen (O2) concentration of an oxygen/nitrogen (N2) mixture flowing through the
      coal sample was 3, 5, 10, 15, and 21%, respectively. The temperature at the
      center of the coal sample was continuously monitored, while the CO, CO2, and O2
      concentrations of the exit gas were continuously measured. The results indicate
      that the CO and CO2 concentrations and the CO/CO2 ratio increased when the
      initial temperature was increased. As the inlet O2 concentration increased, the
      CO and CO2 concentrations increased, while the CO/CO2 ratios tended to converge
      to the same value. The ratio of CO/CO2 was found to be independent of coal
      properties, approaching a constant value of 0.2. The maximum CO production rate
      correlated well with the maximum coal temperature rise. The apparent order of
      reaction for coal oxidation was estimated to be between 0.52 and 0.72. The
      experimental results in this study could be used for early detection and
      evaluation of a spontaneous heating in underground coal mines.

PMID- 26203212
TI  - The Relationship Between Peer, Parent, and Grandparent Norms and Intentions to
      Use Substances for Urban American Indian Youth.
AB  - Peer, parent, and grandparent norms may be a protective factor for American
      Indian (AI) youth intentions to use substances, but little research has explored
      these influences on urban AI youth. Using OLS regression, a secondary data
      analysis examined the relationship between peer, parent and grandparent substance
      use norms, and intentions to use substances (N = 148). Findings indicated that
      grandparent and peer norms were the strongest predictors of intentions to use
      substances. Implications of these results include the need for concerted,
      culturally focused efforts that address AI youth substance use by targeting AI
      peer and family networks.

PMID- 26203213
TI  - Results of endocapsular phacofracture debulking of hard cataracts.
AB  - PURPOSE/AIM OF THE STUDY: To present a phacoemulsification technique for hard
      cataracts and compare postoperative results using two different ultrasonic tip
      motions during quadrant removal. MATERIALS AND METHODS: A phacoemulsification
      technique which employs in situ fracture and endocapsular debulking for hard
      cataracts is presented. The prospective study included 56 consecutive cases of
      hard cataract (LOCS III NC [Lens Opacification Classification System III, nuclear
      color], average 4.26), which were operated using the Infiniti machine and the
      Partial Kelman tip. Longitudinal tip movement was used for sculpting for all
      cases which were randomized to receive longitudinal or torsional/interjected
      longitudinal (Intelligent Phaco [IP]) strategies for quadrant removal.
      Measurements included cumulative dissipated energy (CDE), 3 months postoperative
      surgically induced astigmatism (SIA), and corneal endothelial cell density (ECD)
      losses. RESULTS: No complications were recorded in any of the cases. Respective
      overall and longitudinal vs IP means were as follows: CDE, 51.6+/-15.6 and 55.7+/
      15.5 vs 48.6+/-15.1; SIA, 0.36+/-0.2 D and 0.4+/-0.2 D vs 0.3+/-0.2 D; and mean
      ECD loss, 4.1%+/-10.8% and 5.9%+/-13.4% vs 2.7%+/-7.8%. The differences between
      longitudinal and IP were not significant for any of the three categories.
      CONCLUSION: The endocapsular phacofracture debulking technique is safe and
      effective for phacoemulsification of hard cataracts using longitudinal or
      torsional IP strategies for quadrant removal with the Infiniti machine and
      Partial Kelman tip.

PMID- 26203214
TI  - The clinical utility of new combination phenylephrine/ketorolac injection in
      cataract surgery.
AB  - The maintenance of mydriasis throughout cataract extraction surgery and the
      control of ocular inflammation are crucial for successful surgical outcomes. The
      development of miosis during cataract surgery compromises the visualization of
      the surgical field and working space for surgeons. This may lead to complications
      that include posterior capsular tear and associated vitreous loss, longer
      surgical time, and postoperative inflammation. Postoperative inflammation is
      often uncomfortable and frustrating for patients. It causes pain, redness, and
      photophobia. This compromises the best-uncorrected vision following surgery and
      often leads to multiple clinic visits. This article examines the literature
      published on the current treatments used to manage mydriasis, pain, and
      inflammation in cataract extraction surgery. Combination phenylephrine/ketorolac
      injection offers an exciting new class of medication for use in cataract surgery.
      With the recent approval of OmidriaTM (combination of phenylephrine 1% and
      ketorolac 0.3%) by the US Food and Drug Administration (FDA) for intraocular use,
      we review the clinical utility of this new combination injection in cataract
      surgery. PubMed, MEDLINE, and conference proceedings were searched for the
      relevant literature using a combination of the following search terms: cataract
      extraction surgery, pupil dilation (mydriasis), miosis, phenylephrine, ketorolac,
      OmidriaTM, intracameral mydriatic. Relevant articles were reviewed and their
      references checked for further relevant literature. All abstracts were reviewed
      and full texts retrieved where available. 

PMID- 26203215
TI  - Real-world assessment of intravitreal dexamethasone implant (0.7 mg) in patients
      with macular edema: the CHROME study.
AB  - BACKGROUND: The purpose of this study was to evaluate the real-world use,
      efficacy, and safety of one or more dexamethasone intravitreal implant(s) 0.7 mg
      (DEX implant) in patients with macular edema (ME). METHODS: This was a
      retrospective cohort study of patients with ME secondary to retinal disease
      treated at ten Canadian retina practices, including one uveitis center. Best
      corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular
      pressure (IOP), glaucoma and cataract surgery, and safety data were collected
      from the medical charts of patients with >=3 months of follow-up after the
      initial DEX implant. RESULTS: One hundred and one patient charts yielded data on
      120 study eyes, including diagnoses of diabetic ME (DME) (n=34), retinal vein
      occlusion (RVO, n=30; branch in 19 and central in 11), and uveitis (n=23).
      Patients had a mean age of 60.9 years, and 73.3% of the study eyes had ME for a
      duration of >=12 months prior to DEX implant injection(s). Baseline mean (+/-
      standard error) BCVA was 0.63+/-0.03 logMAR (20/86 Snellen equivalents) and mean
      CRT was 474.4+/-18.2 MUm. The mean number of DEX implant injections was 1.7+/-0.1
      in all study eyes; 44.2% of eyes had repeat DEX implant injections (reinjection
      interval 2.3-4.9 months). The greatest mean peak changes in BCVA lines of vision
      occurred in study eyes with uveitis (3.3+/-0.6, P<0.0001), followed by RVO (1.3+/
      0.5, P<0.01) and DME (0.7+/-0.5, P>0.05). Significant decreases in CRT were
      observed: -255.6+/-43.6 MUm for uveitis, -190.9+/-23.5 MUm for DME, and -160.7+/
      39.6 MUm for RVO (P<0.0001 for all cohorts). IOP increases of >=10 mmHg occurred
      in 20.6%, 24.1%, and 22.7% of DME, RVO, and uveitis study eyes, respectively. IOP
      lowering medication was initiated in 29.4%, 16.7%, and 8.7% of DME, RVO, and
      uveitis study eyes, respectively. Glaucoma surgery was performed in 1.7% of all
      study eyes and cataract surgery in 29.8% of all phakic study eyes receiving DEX
      implant(s). CONCLUSION: DEX implant(s) alone or combined with other treatments
      and/or procedures resulted in functional and anatomic improvements in long
      standing ME associated with retinal disease.

PMID- 26203216
TI  - Evaluation of the effect of intravitreal ranibizumab injections in patients with
      neovascular age related macular degeneration on retinal nerve fiber layer
      thickness using optical coherence tomography.
AB  - PURPOSE: To evaluate the effect of repeated intravitreal ranibizumab injections
      for neovascular age related macular degeneration (nAMD) on the retinal nerve
      fiber layer (RNFL) thickness using optical coherence tomography. DESIGN: A
      prospective observational cohort study of patients with nAMD. METHODS: Thirty
      eyes of 30 patients with nAMD were selected. All patients received three
      ranibizumab injections and underwent scans using the fast RNFL thickness protocol
      (Stratus optical coherence tomography) before starting the first injection and 1
      month after the third injection. The RNFL thickness measurements prior to the
      injections and after the third injection were used for the analysis. We also
      evaluated the effect of the lens status as well as the type of choroidal
      neovascular membrane on RNFL thickness measurements pre- and post-injection. Pre-
      and post-injection average and individual quadrant RNFL thickness were measured
      and statistically analyzed. RESULTS: The mean (+/- standard deviation) pre
      injection RNFL thickness was 90.8+/-18. The mean (+/- standard deviation) post
      injection RNFL thickness was 91.03+/-15. The pre- and post-injection values of
      the mean RNFL thickness were not statistically significant. Likewise, the pre-
      and post-injection values for RNFL thickness in the different quadrants were not
      statistically significant. There was no statistical significance for the lens
      status or the type of choroidal neovascular membrane on the RNFL thickness.
      CONCLUSION: Repeated ranibizumab injections in nAMD appear to have no harmful
      effect on the RNFL thickness in the short term, in spite of the proven
      neurotrophic effect of vascular endothelial growth factor. Nevertheless, the
      safety profile of ranibizumab injections in nAMD needs to be further evaluated in
      a large multicenter trial with special emphasis on the long-term effects on the
      retina and optic nerve.

PMID- 26203217
TI  - Prevalence of comorbid retinal disease in patients with glaucoma at an academic
      medical center.
AB  - BACKGROUND: Patients with various retinal diseases and patients who have
      undergone retinal procedures and surgeries have an increased risk of developing
      ocular hypertension and glaucoma. Little is known about the epidemiology of
      comorbid retinal diseases in glaucoma patients. This study evaluated the
      prevalence of retinal comorbidities in a population of patients with five types
      of glaucoma. METHODS: A longitudinal, retrospective study was conducted using
      International Classification of Disease (ICD-9) billing records from 2003 to 2010
      at an academic medical center. Patients were classified as having primary open
      angle glaucoma (POAG), low tension open-angle glaucoma (NTG), pigmentary open
      angle glaucoma, chronic-angle closure glaucoma (CACG), or pseudoexfoliation
      glaucoma (PXG) if they had at least three clinic visits with the same ICD-9 code.
      Patients were classified as having a retinal comorbidity if they had two visits
      with the same code. Variables were analyzed with the independent t-test, chi (2)
      test, analysis of variance, or Fisher's exact test. RESULTS: A total of 5,154
      patients had glaucoma, and 14.8% of these had a retinal comorbidity. The
      prevalence of comorbid retinal disease was higher in patients with POAG (15.7%)
      than in those with NTG (10.7%), PXG (10.1%), or pigmentary open-angle glaucoma
      (3.7%; P<0.05). Two hundred and two patients had diabetic retinopathy, with POAG
      patients (4.5%) having a higher prevalence than those with CACG (1.4%) or PXG
      (0.6%; P<0.001). There were 297 patients who had macular degeneration and both
      POAG (2.0%) and PXG patients (2.9%) had a higher prevalence of nonexudative
      macular degeneration than those with CACG (0%; P<0.01). Patients with comorbid
      retinal disease had a higher prevalence of blindness and low vision than those
      without comorbid retinal disease (1.97% versus 1.02%, P=0.02). CONCLUSION: The
      high prevalence of comorbid retinal disease and the nearly twofold increase in
      blindness and low vision in this population demonstrate the need for
      ophthalmologists to determine if patients have multiple etiologies for their
      vision loss. The higher prevalence of certain retinal diseases in POAG patients
      may reflect common pathophysiological processes that warrant further
      investigation.

PMID- 26203219
TI  - Clinical outcomes of wavefront-guided laser in situ keratomileusis to treat
      moderate-to-high astigmatism.
AB  - PURPOSE: The purpose of this study was to evaluate the refractive and visual
      outcomes of wavefront-guided laser in situ keratomileusis (LASIK) in eyes with
      myopic astigmatism and cylindrical component >=2.0 diopter (D). METHODS: In this
      retrospective study, 611 eyes that underwent LASIK for simple or compound myopic
      astigmatism were analyzed. Preoperative refractive cylinder ranged from -2.00 D
      to -6.00 D (mean -2.76+/-0.81 D), and the sphere was between 0.00 D and -9.75 D
      (mean -2.79+/-2.32 D). Predictability, visual outcomes, and vector analysis of
      changes in refractive astigmatism were evaluated. RESULTS: At 3 months after
      LASIK, 83.8% of eyes had uncorrected distance visual acuity of 20/20 or better,
      90.3% had manifest spherical equivalent within +/-0.50 D, and 79.1% had residual
      refractive cylinder within +/-0.50 D of intended correction. The mean correction
      ratio for refractive cylinder was 0.92+/-0.14, the mean error of angle was -0.45
      degrees +/-2.99 degrees , and the mean error vector was 0.37+/-0.38 D. A
      statistically significant correlation was found between the error of magnitude
      (arithmetic difference in the magnitudes between surgically induced refractive
      correction and intended refractive correction) and the intended refractive
      correction (r=0.26, P<0.01). CONCLUSION: Wavefront-guided LASIK for the
      correction of myopic astigmatism is safe, effective, and predictable.

PMID- 26203218
TI  - Levels of thrombopoietin in aqueous humor of patients with noninfectious acute
      anterior uveitis.
AB  - PURPOSE: To measure thrombopoietin (TPO) levels in the serum and aqueous humors
      of patients with noninfectious acute anterior uveitis. METHODS: A prospective,
      comparative, controlled study. Serum and aqueous humors were obtained from the
      eyes of 16 patients with noninfectious acute anterior uveitis. TPO levels were
      measured using an enzyme-linked immunosorbent assay (ELISA). The results obtained
      were compared with those of a control group. RESULTS: Serum concentrations of TPO
      were not significantly different between control individuals and patients with
      active anterior uveitis. Aqueous humor TPO levels were 54.46+/-16.24 pg/mL in the
      eyes of patients with uveitis, and 34.32+/-11.63 pg/mL in the eyes of controls.
      The difference between the two groups was significant (Mann-Whitney U-test for
      independent data, P=0.0008), with uveitis patients exhibiting significantly
      higher levels of TPO. CONCLUSION: The high levels of TPO in the aqueous humors of
      uveitis patients points toward a cytoprotective role of this factor in
      inflammatory repair processes and the recovery of tissue homeostasis.

PMID- 26203220
TI  - Detection of pigment epithelial detachment vascularization in age-related macular
      degeneration using phase-variance OCT angiography.
AB  - PURPOSE: To demonstrate the use of phase-variance optical coherence tomography
      (PV-OCT) angiography for detection of pigment epithelial detachment (PED)
      vascularization in age-related macular degeneration (AMD). PATIENTS AND METHODS:
      Patients with PEDs and exudative AMD were evaluated by the Retina Services at the
      University of California, Davis, and the University of California, San Francisco.
      Each subject underwent fluorescein angiography and structural optical coherence
      tomography (OCT). Phase-variance OCT analysis was used to create angiographic
      images of the retinal and choroidal vasculature. PV-OCT-generated B-scans were
      superimposed on structural OCT B-scans to allow easy identification of perfused
      vascular structures. RESULTS: Three patients with vascularized PEDs were imaged
      with PV-OCT, and each was found to have a vascular signal extending from the
      choroid into the hyperreflective substance of the PED. Two patients who had no
      evidence of PED vascularization on fluorescein angiography did not have vascular
      signals within their PEDs on PV-OCT. CONCLUSION: Structural OCT and PV-OCT images
      can be combined to create composite B-scans that offer high-resolution views of
      the retinal tissue along with dynamic vascular visualization. This technique
      offers a fast, noninvasive method for detecting vascularization of PEDs in AMD
      and may aid in the early detection of neovascular disease.

PMID- 26203221
TI  - Giant-cell tumor of bone: treatment options and role of denosumab.
AB  - Giant-cell tumor of bone is a rare, locally aggressive tumor that typically
      occurs in the bones of skeletally mature young adults in their second to fourth
      decades. Traditionally, surgery has been the mainstay of therapy for this
      disease, but the disease can recur even with optimal procedures. Furthermore, it
      may occur in locations where a surgical approach would be morbid. The maturation
      of the understanding of the role of the receptor activator of nuclear factor
      kappaB ligand (RANKL) in the pathophysiology of giant-cell tumor of bone has led
      to the use of denosumab, a monoclonal antibody against RANKL, in this disease. In
      2013, the US Food and Drug Administration approved denosumab for use in patients
      with recurrent/unresectable/metastatic giant-cell tumor of bone or for patients
      in whom surgery would be morbid. 

PMID- 26203222
TI  - Synergistic antitumor effect of adenovirus armed with Drosophila melanogaster
      deoxyribonucleoside kinase and nucleoside analogs for human breast carcinoma in
      vitro and in vivo.
AB  - BACKGROUND: Suicide gene therapy in cancer can selectively kill tumors without
      damaging normal tissues. Drosophila melanogaster multisubstrate
      deoxyribonucleoside kinase (Dm-dNK), an original suicide kinase, makes use of the
      carcinomatous suicide gene therapy for broader substrate specificity and a higher
      catalytic rate. METHODS: To enhance the anti-tumor efficacy of Dm-dNK and
      maintain its substrate specificity and safety control in the meantime, the
      conditionally replicative gene-viral system, ZD55-dNK (which contains the
      selective replication adenovirus, ZD55, encoded with Dm-dNK), was investigated in
      pushing a deeper development of this strategy. Selective replication, cell
      killing efficacy, and cytotoxicity, in combination with chemotherapy, were
      applied to two breast cell lines (MDA231 and MCF7 cells), two normal cell lines
      (WI38 and MRC5 cells), and the MCF7 xenograft model in vivo. RESULTS: The
      preclinical study showed that ZD55-dNK, combined with 2',2'-difluorodeoxycytidine
      (DFDC), synergistically inhibited adenovirus replication in vitro but maintained
      specifically cancer cell killing efficacy. ZD55-dNK also greatly improved the
      antineoplastic effect in vitro and in breast cancer xenograft in vivo.
      CONCLUSION: The concomitant use of ZD55-dNK and DFDC is possibly a novel and
      promising approach to breast cancer treatment, and further investigation on the
      safe control of excessive virus replication and the efficacy of this approach in
      humans is warranted.

PMID- 26203223
TI  - Effect of Clausena excavata Burm. f. (Rutaceae) leaf extract on wound healing and
      antioxidant activity in rats.
AB  - Clausena excavata is a well-known plant used in folkloric medicine for the
      treatment of different ailments. This study aimed to determine the in vitro
      cytoxicity of its leaf solvent extracts as well as the in vivo wound healing and
      antioxidant activities of the methanolic extracts of C. excavata (MECE). HaCaT
      (keratocyte) and Vero cell lines were used for evaluation of the in vitro
      cytotoxic effects, while the in vivo wound healing and antioxidant activities
      were determined in skin wounds inflicted on rats. Twenty adult male Sprague
      Dawley rats were divided into five groups of four animals each. Approximately
      3.14 cm(2) excisional wound was inflicted on the nape of each rat following
      anesthesia. The treatment groups received topical application of MECE at 50 mg/mL
      (MECE-LD [low dose]), 100 mg/mL (MECE-MD [medium dose]), and 200 mg/mL (MECE-HD
      [high dose]), while the negative control group was treated with gum acacia in
      normal saline and the positive control group with intrasite gel. Wound
      contraction was evaluated on days 5, 10, and 15 after wound infliction, and
      tissue from wound area was collected at day 15 post-wound infliction for
      antioxidant enzyme evaluation and histopathological analyses. Generally, Vero
      cells were more resistant to the cytotoxic effects of the solvent extracts as
      compared with HaCaT cells. Chloroform (CH) and ethyl acetate (EA) extracts of C.
      excavata were toxic to HaCaT cells at 200 and 400 ug/mL, but the same
      concentrations showed higher (P<0.05) viability in Vero cells. There was
      significantly (P<0.01) greater wound contraction at days 10 and 15 post-wound
      infliction in all the treatment groups than in the control groups.
      Histopathologically, the MECE-HD-treated wound showed significantly (P<0.05)
      lesser inflammatory cell proliferation, degeneration, and distribution of
      granulation tissue than other groups. Similarly, the degree of collagen
      maturation, angiogenesis, and collagen distribution were significantly (P<0.05)
      lower in MECE-HD than in other groups. The MECE-HD, MECE-MD, and intrasite
      treatment groups showed a significantly (P<0.05) higher number of VEGF-positive
      and TGF-beta1-positive cells in the skin wound than the control groups. The
      activities of superoxide dismutase and catalase were significantly (P<0.01)
      higher in the MECE-HD and intrasite treatment groups than in the other groups.
      Lipid peroxidase activity of the treated groups was significantly (P<0.01) lower
      than that in the control group. The study showed that MECE is a potent wound
      healing agent through anti-inflammatory and antioxidant effects that enhanced the
      rate of wound contraction, re-epithelialization, and collagen deposition. The
      effect of MECE is suggested to be due to its high polyphenolic compound content. 

PMID- 26203224
TI  - Wound healing: a new perspective on glucosylated tetrahydrocurcumin.
AB  - Wound healing represents a dynamic set of coordinated physiological processes
      observed in response to tissue injury. Several natural products are known to
      accelerate the process of wound healing. Tetrahydrocurcumin (THC), an in vivo
      biotransformed product/metabolite of curcumin, is known to exhibit a wide
      spectrum of biological activities similar to those of native curcuminoids. The
      poor bioavailability of these curcuminoids limits their clinical applications.
      The present study highlights the percutaneous absorption and wound healing
      activity of glucosyl-conjugated THC (glucosyl-THC) in male Wistar rats. A high
      plasma concentration of glucosyl-THC (4.35 MUg/mL) was found in rats 3 hours
      after application. A significant enhanced wound healing activity and reduced
      epithelialization time were observed in rats that received glucosyl-THC. This may
      have been due to the improved bioavailability of the glucosyl compound. The
      nonstaining and lack of skin-sensitive side effects render the bioconjugated
      glucosyl-THC a promising therapeutic compound in the management of excision
      wounds and in cosmetic applications, in the near future. 

PMID- 26203225
TI  - Apparent Km of mitochondria for oxygen computed from Vmax measured in
      permeabilized muscle fibers is lower in water enriched in oxygen by electrolysis
      than injection.
AB  - BACKGROUND: It has been suggested that oxygen (O2) diffusion could be favored in
      water enriched in O2 by a new electrolytic process because of O2 trapping in
      water superstructures (clathrates), which could reduce the local pressure/content
      relationships for O2 and facilitate O2 diffusion along PO2 gradients. MATERIALS
      AND METHODS: Mitochondrial respiration was compared in situ in saponin-skinned
      fibers isolated from the soleus muscles of Wistar rats, in solution enriched in
      O2 by injection or the electrolytic process 1) at an O2 concentration decreasing
      from 240 umol/L to 10 umol/L (132 mmHg to 5 mmHg), with glutamate-malate or N, N,
      N', N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD)-ascorbate (with
      antimycin A) as substrates; and 2) at increasing adenosine diphosphate (ADP)
      concentration with glutamate-malate as substrate. RESULTS: As expected, maximal
      respiration decreased with O2 concentration and, when compared to glutamate
      malate, the apparent Km O2 of mitochondria for O2 was significantly lower with
      TMPD-ascorbate with both waters. However, when compared to the water enriched in
      O2 by injection, the Km O2 was significantly lower with both electron donors in
      water enriched in O2 by electrolysis. This was not associated with any increase
      in the sensitivity of mitochondria to ADP; no significant difference was observed
      for the Km ADP between the two waters. CONCLUSION: In this experiment, a higher
      affinity of the mitochondria for O2 was observed in water enriched in O2 by
      electrolysis than by injection. This observation is consistent with the
      hypothesis that O2 diffusion can be facilitated in water enriched in O2 by the
      electrolytic process.

PMID- 26203226
TI  - Depot injectable biodegradable nanoparticles loaded with recombinant human bone
      morphogenetic protein-2: preparation, characterization, and in vivo evaluation.
AB  - OBJECTIVE: The aim of this study is to utilize the biocompatibility
      characteristics of biodegradable polymers, viz, poly lactide-co-glycolide (PLGA)
      and polycaprolactone (PCL), to prepare sustained-release injectable nanoparticles
      (NPs) of bone morphogenetic protein-2 (BMP-2) for the repair of alveolar bone
      defects in rabbits. The influence of formulation parameters on the functional
      characteristics of the prepared NPs was studied to develop a new noninvasive
      injectable recombinant human BMP-2 (rhBMP-2) containing grafting material for the
      repair of alveolar bone clefts. MATERIALS AND METHODS: BMP-2 NPs were prepared
      using a water-in-oil-in-water double-emulsion solvent evaporation/extraction
      method. The influence of molar ratio of PLGA to PCL on a suitable particle size,
      encapsulation efficiency, and sustained drug release was studied. Critical size
      alveolar defects were created in the maxilla of 24 New Zealand rabbits divided
      into three groups, one of them treated with 5 MUg/kg of rhBMP-2 NP formulations.
      RESULTS: The results found that NPs formula prepared using blend of PLGA and PCL
      in 4:2 (w/w) ratio showed the best sustained-release pattern with lower initial
      burst, and showed up to 62.7% yield, 64.5% encapsulation efficiency, 127 nm size,
      and more than 90% in vitro release. So, this formula was selected for scanning
      electron microscope examination and in vivo evaluation. Histomorphometric
      analysis showed 78% trabecular bone fill, mostly mature bone in the defects
      treated with rhBMP-2 in NPs within 6 weeks. CONCLUSION: The prepared NPs
      prolonged the release and the residence time of rhBMP-2 in rabbits, which led to
      the formation of adequate bone in critical size alveolar bone defects in 6 weeks.
      This noninvasive method has application for the primary restoration of alveolar
      bone defects.

PMID- 26203227
TI  - Selective oropharyngeal decontamination versus selective digestive
      decontamination in critically ill patients: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Selective digestive decontamination (SDD) and selective oropharyngeal
      decontamination (SOD) are associated with reduced mortality and infection rates
      among patients in intensive care units (ICUs); however, whether SOD has a
      superior effect than SDD remains uncertain. Hence, we conducted a meta-analysis
      of randomized controlled trials (RCTs) to compare SOD with SDD in terms of
      clinical outcomes and antimicrobial resistance rates in patients who were
      critically ill. METHODS: RCTs published in PubMed, Embase, and Web of Science
      were systematically reviewed to compare the effects of SOD and SDD in patients
      who were critically ill. Outcomes included day-28 mortality, length of ICU stay,
      length of hospital stay, duration of mechanical ventilation, ICU-acquired
      bacteremia, and prevalence of antibiotic-resistant Gram-negative bacteria.
      Results were expressed as risk ratio (RR) with 95% confidence intervals (CIs),
      and weighted mean differences (WMDs) with 95% CIs. Pooled estimates were
      performed using a fixed-effects model or random-effects model, depending on the
      heterogeneity among studies. RESULTS: A total of four RCTs involving 23,822
      patients met the inclusion criteria and were included in this meta-analysis.
      Among patients whose admitting specialty was surgery, cardiothoracic surgery
      (57.3%) and neurosurgery (29.7%) were the two main types of surgery being
      performed. Pooled results showed that SOD had similar effects as SDD in day-28
      mortality (RR = 1.03; 95% CI: 0.98, 1.08; P = 0.253), length of ICU stay (WMD =
      0.00 days; 95% CI: -0.2, 0.2; P = 1.00), length of hospital stay (WMD = 0.00
      days; 95% CI: -0.65, 0.65; P = 1.00), and duration of mechanical ventilation (WMD
      =1.01 days; 95% CI: -0.01, 2.02; P = 0.053). On the other hand, compared with
      SOD, SDD had a lower day-28 mortality in surgical patients (RR =1.11; 95% CI:
      1.00, 1.22; P = 0.050), lower incidence of ICU-acquired bacteremia (RR = 1.38;
      95% CI: 1.24, 1.54; P = 0.000), and lower rectal carriage of aminoglycosides (RR
      = 2.08; 95% CI: 1.68, 2.58; P = 0.000), ciprofloxacin-resistant Gram-negative
      bacteria (RR = 1.84; 95% CI: 1.48, 2.29; P = 0.000), and respiratory carriage of
      third-generation cephalosporin-resistant Gram-negative bacteria (RR = 2.50; 95%
      CI: 1.78, 3.5; P = 0.000). CONCLUSION: SOD has similar effects as SDD in clinical
      outcomes, but has higher incidence of ICU-acquired bacteremia, and higher
      carriage of antibiotic-resistant Gram-negative bacteria. However, due to the high
      cost of SDD and the increased risk of development of antibiotic resistance with
      the widespread use of cephalosporins in SDD, we would recommend SOD as
      prophylactic antibiotic regimens in patients in the ICU. More well-designed,
      large-scale RCTs are needed to confirm our findings.

PMID- 26203228
TI  - A meta-analysis for C-X-C chemokine receptor type 4 as a prognostic marker and
      potential drug target in hepatocellular carcinoma.
AB  - Chemokines (CKs), small proinflammatory chemoattractant cytokines that bind to
      specific G-protein coupled seven-span transmembrane receptors, are major
      regulators of cell trafficking and adhesion. C-X-C chemokine receptor type 4
      (CXCR4) has gained tremendous attention over the last decade, since it was found
      to be upregulated in a wide variety of cancer types, including hepatocellular
      carcinoma (HCC). The clinical relevance of expression of CXCR4 in HCC remains
      controversial; our aim was to identify the precise relationship of CXCR4 to
      prognosis and clinicopathological features. We searched the database from
      MEDLINE, PubMed, Web of Science, Scopus and Embase and then conducted a meta
      analysis from publications met the inclusion criteria for the qualitative study.
      Our data showed that 1) CXCR4 is overexpressed in HCC tissues but not in normal
      hepatic tissue, OR = 84.26, 95% confidence interval (CI) = 11.86-598.98, P <
      0.0001. CXCR4 expression is higher in HCC than those in cirrhosis as well, OR =
      20.71, 95% CI = 7.61-56.34, P < 0.00001. 2) The expression levels of CXCR4 does
      not increase during local progression, however, CXCR4 expression increases the
      risk of distant metastases in HCC, OR = 5.84, 95% CI = 2.84-12.00, P < 0.00001.
      3) High levels of CXCR4 gene expression are associated with worse survival in
      HCC, HR = 0.18, 95% CI = 0.10-0.32, Z = 5.77, P < 0.00001. These data indicate
      that CXCR4 expression correlates with an increased risk and worse survival in HCC
      patients. The aberrant CXCR4 expression plays an important role in the
      carcinogenesis and metastasis of HCC. Our conclusion also supports that the
      promise of CXCR4 signaling pathway blockade as a potential strategy for HCC
      patients.

PMID- 26203229
TI  - 2-acetylphenol analogs as potent reversible monoamine oxidase inhibitors.
AB  - Based on a previous report that substituted 2-acetylphenols may be promising
      leads for the design of novel monoamine oxidase (MAO) inhibitors, a series of C5
      substituted 2-acetylphenol analogs (15) and related compounds (two) were
      synthesized and evaluated as inhibitors of human MAO-A and MAO-B. Generally, the
      study compounds exhibited inhibitory activities against both MAO-A and MAO-B,
      with selectivity for the B isoform. Among the compounds evaluated, seven
      compounds exhibited IC50 values <0.01 uM for MAO-B inhibition, with the most
      selective compound being 17,000-fold selective for MAO-B over the MAO-A isoform.
      Analyses of the structure-activity relationships for MAO inhibition show that
      substitution on the C5 position of the 2-acetylphenol moiety is a requirement for
      MAO-B inhibition, and the benzyloxy substituent is particularly favorable in this
      regard. This study concludes that C5-substituted 2-acetylphenol analogs are
      potent and selective MAO-B inhibitors, appropriate for the design of therapies
      for neurodegenerative disorders such as Parkinson's disease. 

PMID- 26203230
TI  - The effect of carvedilol and propranolol on portal hypertension in patients with
      cirrhosis: a meta-analysis.
AB  - PURPOSE: Several randomized controlled clinical trials have been conducted to
      investigate the role of carvedilol and propranolol on the effect of portal
      pressure in patients with cirrhosis, leading to controversial results. Current
      meta-analysis was performed to compare the efficacy of the two drugs on portal
      pressure. PATIENTS AND METHODS: Two-hundred and ninety eligible patients were
      recruited. Published studies were selected based on PubMed, the Cochrane Library,
      Chinese Journal Full-text Database, and Wanfang Database. The outcome
      measurements included the mean difference (MD) in the percentage of hepatic vein
      pressure gradient reduction (%HVPG reduction), the risk ratio (RR) of
      nonresponders in hemodynamic assessment, and the percentage of mean arterial
      pressure reduction (%MAP reduction). Subgroup analysis was performed. RESULTS:
      Seven trials were identified (including five acute and three long-term drug
      administration randomized controlled trials). A summary of pooled MD between the
      %HVPG reduction is as follows: overall -8.62 (confidence interval [CI] -11.76, 
      5.48, P<0.00001), acute -10.05 (CI -14.24, -5.86, P<0.00001), and long term -6.80
      (CI -11.53, -2.07, P=0.005), while summary of pooled RR of hemodynamic
      nonresponders with carvedilol was as follows: overall 0.64 (CI 0.51, 0.81,
      P=0.0002), acute 0.63 (CI 0.47, 0.85, P=0.002), and long term 0.67 (CI 0.47,
      0.97, P=0.03). Both of the outcome measurements favored carvedilol. Significant
      heterogeneity (P<0.1, I (2)=92%) existed between the two treatment groups in %MAP
      reduction. No considerable difference could be observed in the %MAP reduction
      through the poor overlapping CI boundaries. CONCLUSION: Carvedilol has a greater
      portal hypertensive effect than propranolol. Further comparative trials of the
      two drugs are required to identify the effect of MAP reduction.

PMID- 26203231
TI  - Qualitative evaluation of adherence therapy in Parkinson's disease: a
      multidirectional model.
AB  - BACKGROUND: Medication can control the symptoms of Parkinson's disease (PD).
      Despite this, non-adherence with medication is prevalent in PD. Treatments for
      improving adherence with medication have been investigated in many chronic
      conditions, including PD. However, few researchers have evaluated their
      interventions qualitatively. We investigated the acceptability and potential
      mechanism of action of adherence therapy (AT) in PD patients and their
      spouse/carers who received the intervention as part of a randomized controlled
      trial. METHODS: Sixteen participants (ten patients and six spouses/carers) who
      had recently completed the trial were purposely selected in order to cover a
      range of ages and disease severity. Semi-structured interviews were conducted in
      the participants' homes. Data were transcribed and analyzed using a thematic
      approach. A second researcher, naive to PD and AT, analyzed the data
      independently to limit bias. RESULTS: The trial showed that AT significantly
      improved both medication adherence and quality of life in people with PD.
      Specifically, patients who received AT reported improvements in mobility,
      activities of daily living, emotional wellbeing, cognition, communication, and
      body discomfort. General beliefs about medication also significantly improved in
      those who received AT compared with controls. In the current qualitative
      evaluation, a total of 175 codes were generated, which formed eleven subthemes.
      These could be grouped under three overarching themes, ie, perceptions prior to
      AT, positive effects of AT, and attributes of AT. CONCLUSION: This randomized
      controlled trial is the first to investigate AT in PD. The acceptability and
      underlying mechanism of the intervention suggest a new multidirectional model of
      AT in PD which future research should seek to confirm. The findings provide a
      deeper understanding of AT and will allow clinicians to modify the delivery of
      the intervention by acknowledging various pathways to improved outcomes.

PMID- 26203232
TI  - Beneficial effects of training at the anaerobic threshold in addition to
      pharmacotherapy on weight loss, body composition, and exercise performance in
      women with obesity.
AB  - OBJECTIVE: The aim of this study was to determine and compare the effects of
      weight loss achieved through orlistat therapy alone or a combination of orlistat
      and an aerobic exercise training program on aerobic fitness and body composition
      in obese females. METHODS: Twenty-eight obese patients were randomly assigned to
      receive 12-week treatment with hypocaloric diet-orlistat or diet-orlistat
      exercise. Each participant performed an incremental ramp exercise test every 4
      weeks to measure aerobic fitness. Fourteen participants performed continuous
      exercise (approximately 45 minutes per session) at a work rate corresponding to
      the anaerobic threshold three times per week. RESULTS: A decrease in the fat mass
      to body weight ratio of 3.8% (P=0.006) was observed at the end of the 12 weeks in
      the orlistat group, while a decrease of 9.5% (P=0.001) was seen in the orlistat
      exercise group. Maximal exercise capacity increased by 46.5% in the orlistat
      exercise group and by 19.5% in the orlistat group. CONCLUSION: While orlistat
      therapy resulted in an improvement in body composition and aerobic fitness at the
      end of the 12-week period, its combination with exercise training provided
      improvements in the same parameters within the first 4 weeks of the study. These
      additional beneficial effects of combining aerobic exercise with orlistat therapy
      are important with regards to obesity-associated risk factors.

PMID- 26203233
TI  - Older adults' preferences for colorectal cancer-screening test attributes and
      test choice.
AB  - BACKGROUND: Understanding which attributes of colorectal cancer (CRC) screening
      tests drive older adults' test preferences and choices may help improve decision
      making surrounding CRC screening in older adults. MATERIALS AND METHODS: To
      explore older adults' preferences for CRC-screening test attributes and screening
      tests, we conducted a survey with a discrete choice experiment (DCE), a directly
      selected preferred attribute question, and an unlabeled screening test-choice
      question in 116 cognitively intact adults aged 70-90 years, without a history of
      CRC or inflammatory bowel disease. Each participant answered ten discrete choice
      questions presenting two hypothetical tests comprised of four attributes: testing
      procedure, mortality reduction, test frequency, and complications. DCE responses
      were used to estimate each participant's most important attribute and to simulate
      their preferred test among three existing CRC-screening tests. For each
      individual, we compared the DCE-derived attributes to directly selected
      attributes, and the DCE-derived preferred test to a directly selected unlabeled
      test. RESULTS: Older adults do not overwhelmingly value any one CRC-screening
      test attribute or prefer one type of CRC-screening test over other tests.
      However, small absolute DCE-derived preferences for the testing procedure
      attribute and for sigmoidoscopy-equivalent screening tests were revealed. Neither
      general health, functional, nor cognitive health status were associated with
      either an individual's most important attribute or most preferred test choice.
      The DCE-derived most important attribute was associated with each participant's
      directly selected unlabeled test choice. CONCLUSION: Older adults' preferences
      for CRC-screening tests are not easily predicted. Medical providers should
      actively explore older adults' preferences for CRC screening, so that they can
      order a screening test that is concordant with their patients' values. Effective
      interventions are needed to support complex decision making surrounding CRC
      screening in older adults.

PMID- 26203234
TI  - Multidisciplinary approach to the diagnosis and management of patients with
      peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is frequently diagnosed after permanent damage
      has occurred, resulting in a high rate of morbidity, amputation, and loss of
      life. Early and ongoing diagnosis and treatment is required for this progressive
      disease. Lifestyle modifications can prevent or delay disease progression and
      improve symptoms. Limb-sparing endovascular interventions can restore circulation
      based on appropriate diagnostic testing to pinpoint vascular targets, and
      intervention must occur as early as possible to ensure optimal clinical outcomes.
      An algorithm for the diagnosis and management of PAD was developed to enable a
      collaborative approach between the family practice and primary care physician or
      internist and various specialists that may include a diabetologist,
      endocrinologist, smoking cessation expert, hypertension and lipid specialist,
      endovascular interventionalist, vascular surgeon, orthopedist, neurologist, nurse
      practitioner, podiatrist, wound healing expert, and/or others. A
      multidisciplinary team working together has the greatest chance of providing
      optimal care for the patient with PAD and ensuring ongoing surveillance of the
      patient's overall health, ultimately resulting in better quality of life and
      increased longevity for patients with PAD. 

PMID- 26203235
TI  - Agreement for depression diagnosis between DSM-IV-TR criteria, three validated
      scales, oncologist assessment, and psychiatric clinical interview in elderly
      patients with advanced ovarian cancer.
AB  - BACKGROUND: Depression, a major outcome in cancer patients, is often evaluated by
      physicians relying on their clinical impressions rather than patient self-report.
      Our aim was to assess agreement between patient self-reported depression,
      oncologist assessment (OA), and psychiatric clinical interview (PCI) in elderly
      patients with advanced ovarian cancer (AOC). METHODS: This analysis was a
      secondary endpoint of the Elderly Women AOC Trial 3 (EWOT3), designed to assess
      the impact of geriatric covariates, notably depression, on survival in patients
      older than 70 years of age. Depression was assessed using the Geriatric
      Depression Scale-30 (GDS), the Hospital Anxiety Depression Scale, the distress
      thermometer, the mood thermometer, and OA. The interview guide for PCI was
      constructed from three validated scales: the GDS, the Hamilton Depression Rating
      Scale, and the Montgomery Asberg Depression Rating Scale (MADRS). The Diagnostic
      and Statistical Manual of Mental Disorders, fourth edition, revised (DSM)
      criteria for depression were used as a gold standard. RESULTS: Out of 109
      patients enrolled at 21 centers, 99 (91%) completed all the assessments. Patient
      characteristics were: mean age 78, performance status >=2: 47 (47%). Thirty six
      patients (36%) were identified as depressed by the PCI versus 15 (15%) identified
      by DSM. We found moderate agreement for depression identification between DSM and
      GDS (kappa=0.508) and PCI (kappa=0.431) and high agreement with MADRS
      (kappa=0.663). We found low or no agreement between DSM with the other assessment
      strategies, including OA (kappa=-0.043). Identification according to OA (yes/no)
      resulted in a false-negative rate of 87%. As a screening tool, GDS had the best
      sensitivity and specificity (94% and 80%, respectively). CONCLUSION: The use of
      validated tools, such as GDS, and collaboration between psychologists and
      oncologists are warranted to better identify emotional disorders in elderly women
      with AOC.

PMID- 26203236
TI  - Mutations in presenilin 2 and its implications in Alzheimer's disease and other
      dementia-associated disorders.
AB  - Alzheimer's disease (AD) is the most common form of dementia. Mutations in the
      genes encoding presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor
      protein have been identified as the main genetic causes of familial AD. To date,
      more than 200 mutations have been described worldwide in PSEN1, which is highly
      homologous with PSEN2, while mutations in PSEN2 have been rarely reported. We
      performed a systematic review of studies describing the mutations identified in
      PSEN2. Most PSEN2 mutations were detected in European and in African populations.
      Only two were found in Korean populations. Interestingly, PSEN2 mutations
      appeared not only in AD patients but also in patients with other disorders,
      including frontotemporal dementia, dementia with Lewy bodies, breast cancer,
      dilated cardiomyopathy, and Parkinson's disease with dementia. Here, we have
      summarized the PSEN2 mutations and the potential implications of these mutations
      in dementia-associated disorders. 

PMID- 26203237
TI  - The inspiratory capacity/total lung capacity ratio as a predictor of survival in
      an emphysematous phenotype of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Forced expiratory volume in 1 second (FEV1) grades severity of COPD
      and predicts survival. We hypothesize that the inspiratory capacity/total lung
      capacity (IC/TLC) ratio, a sensitive measure of static lung hyperinflation, may
      have a significant association with survival in an emphysematous phenotype of
      COPD. OBJECTIVES: To access the association between IC/TLC and survival in an
      emphysematous phenotype of COPD. METHODS: We performed a retrospective analysis
      of a large pulmonary function (PF) database with 39,050 entries, from April 1978
      to October 2009. Emphysematous COPD was defined as reduced FEV1/forced vital
      capacity (FVC), increased TLC, and reduced diffusing capacity of the lungs for
      carbon monoxide (DLCO; beyond 95% confidence intervals [CIs]). We evaluated the
      association between survival in emphysematous COPD patients and the IC/TLC ratio
      evaluated both as dichotomous (<=25% vs >25%) and continuous predictors. Five
      hundred and ninety-six patients had reported death dates. RESULTS: Univariate
      analysis revealed that IC/TLC <=25% was a significant predictor of death (hazard
      ratio [HR]: 2.39, P<0.0001). Median survivals were respectively 4.3 (95% CI: 3.8
      4.9) and 11.9 years (95% CI: 10.3-13.2). Multivariable analysis revealed age (HR:
      1.19, 95% CI: 1.14-1.24), female sex (HR: 0.69, 95% CI: 0.60-0.83), and IC/TLC
      <=25% (HR: 1.69, 95% CI: 1.34-2.13) were related to the risk of death. Univariate
      analysis showed that continuous IC/TLC was associated with death, with an HR of
      1.66 (95% CI: 1.52-1.81) for a 10% decrease in IC/TLC. CONCLUSION: Adjusting for
      age and sex, IC/TLC <=25% is related to increased risk of death, and IC/TLC as a
      continuum, is a significant predictor of mortality in emphysematous COPD
      patients.

PMID- 26203238
TI  - Pulmonary hemodynamic profile in chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Few data are available in regards to the prevalence of pulmonary
      hypertension (PH) in the broad spectrum of COPD. This study was aimed at
      assessing the prevalence of PH in a cohort of COPD patients across the severity
      of airflow limitation, and reporting the hemodynamic characteristics at rest and
      during exercise. METHODS: We performed a retrospective analysis on COPD patients
      who underwent right-heart catheterization in our center with measurements
      obtained at rest (n=139) and during exercise (n=85). PH was defined as mean
      pulmonary artery pressure (mPAP) >=25 mmHg and pulmonary capillary wedge pressure
      <15 mmHg. Exercise-induced PH (EIPH) was defined by a ratio of
      DeltamPAP/Deltacardiac output >3. RESULTS: PH was present in 25 patients (18%).
      According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      classification, PH prevalence in GOLD 2 was 7% (3 patients); 25% (14 patients) in
      GOLD 3; and 22% (8 patients) in GOLD 4. Severe PH (mPAP >=35 mmHg) was identified
      in four patients (2.8%). Arterial partial oxygen pressure was the outcome most
      strongly associated with PH (r=-0.29, P<0.001). EIPH was observed in 60 patients
      (71%) and had a similar prevalence in both GOLD 2 and 3, and was present in all
      GOLD 4 patients. Patients with PH had lower cardiac index during exercise than
      patients without PH (5.0+/-1.2 versus 6.7+/-1.4 L/min/m(2), respectively;
      P=0.001). CONCLUSION: PH has a similar prevalence in COPD patients with severe
      and very-severe airflow limitation, being associated with the presence of
      arterial hypoxemia. In contrast, EIPH is highly prevalent, even in moderate COPD,
      and might contribute to limiting exercise tolerance.

PMID- 26203240
TI  - Clinical significance of laryngopharyngeal reflux in patients with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is closely
      associated with gastroesophageal reflux disease (GERD), the clinical significance
      of laryngopharyngeal reflux (LPR) is not fully understood in COPD. METHODS:
      Prospective cohorts were established among 118 patients with COPD from March 2013
      to July 2014. Thirty-two age-matched and sex-matched normal controls, who had
      routine health check-ups during the study period, were included.
      Laryngopharyngeal reflux finding scores (RFS) and reflux symptom index (RSI) for
      LPR were subjected to association analysis with severity and acute exacerbation
      of COPD during the 1-year follow-up. RESULTS: The mean age of patients enrolled
      in the study was 69.2+/-8.8 years, with 93.2% being male. Positive RFS (>7) and
      RSI (>13) were observed in 51 (42.5%) and six patients (5.0%), respectively. RFS
      and RSI were significantly higher in patients with COPD than in normal, healthy
      patients (P<0.001). RFS was significantly correlated with residual volume/total
      lung capacity (%, P=0.048). Scores for diffuse laryngeal edema, erythema, and
      hyperemia were significantly higher in the high-risk group (Global Initiative for
      Chronic Obstructive Lung Disease classification C and D; P=0.025 and P=0.049,
      respectively), while RSI was significantly higher in the more symptomatic group
      (Global Initiative for Chronic Obstructive Lung Disease classification B and D;
      P=0.047). RSI and RFS were significant predictors for severe acute exacerbation
      of COPD (P=0.03 and P=0.047, respectively), while only RSI was associated with
      severity of dyspnea. CONCLUSION: Laryngeal examination and evaluation of
      laryngeal reflux symptom could be a surrogate clinical indicator related to
      severe acute exacerbation of COPD. Further studies of LPR in COPD patients should
      be considered.

PMID- 26203241
TI  - MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance
      survival in an advanced hepatocellular carcinoma model.
AB  - Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers;
      most cases are diagnosed at advanced stages with underlying liver dysfunction and
      are frequently resistant to conventional chemotherapy and radiotherapy. The
      development of tumor-targeting systems may improve treatment outcomes.
      Nanomedicine platforms are of particular interest for enhancing chemotherapeutic
      efficiency, and they include polymeric micelles, which enable targeting of
      multiple drugs to solid tumors, including imaging and therapeutic agents. This
      allows concurrent diagnosis, targeting strategy validation, and efficacy
      assessment. We used polymeric micelles containing the T1-weighted magnetic
      resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd
      DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2
      diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in
      an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected
      into the hepatic artery, and magnetic resonance imaging performance and antitumor
      activity against HCC, as well as adverse drug reactions were assessed. After a
      single administration, the micelles achieved strong and specific tumor contrast
      enhancement, induced high levels of tumor apoptosis, and significantly suppressed
      tumor size and growth. Moreover, the micelles did not induce severe adverse
      reactions and significantly improved survival outcomes in comparison to
      oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded
      micelles are a promising approach for effective diagnosis and treatment of
      advanced HCC. 

PMID- 26203239
TI  - Underrecognized comorbidities of chronic obstructive pulmonary disease.
AB  - COPD is associated with different comorbid diseases, and their frequency
      increases with age. Comorbidities severely impact costs of health care, intensity
      of symptoms, quality of life and, most importantly, may contribute to life span
      shortening. Some comorbidities are well acknowledged and established in doctors'
      awareness. However, both everyday practice and literature searches provide
      evidence of other, less recognized diseases, which are frequently associated with
      COPD. We call them underrecognized comorbidities, and the reason why this is so
      may be related to their relatively low clinical significance, inefficient
      literature data, or data ambiguity. In this review, we describe rhinosinusitis,
      skin abnormalities, eye diseases, different endocrinological disorders, and
      gastroesophageal reflux disease. Possible links to COPD pathogenesis have been
      discussed, if the data were available. 

PMID- 26203242
TI  - Biodegradable double nanocapsule as a novel multifunctional carrier for drug
      delivery and cell imaging.
AB  - Highly-efficient delivery of macromolecules into cells for both imaging and
      therapy (theranostics) remains a challenge for the design of a delivery system.
      Here, we suggested a novel hybrid protein-lipid polymer nanocapsule as an
      effective and nontoxic drug delivery and imaging carrier. The biodegradable
      nanocapsules showed the typical double emulsion features, including fluorescently
      labeled bovine serum albumin shell, oil phase containing poly(lactic-co-glycolic
      acid) and linoleic acid, and inner aqueous phase. The nanocapsules were spherical
      in shape, with an average size of about 180 nm. Proteins packed into the inner
      aqueous phase of the nanocapsules could be delivered into cells with high
      efficiency, and the fluorescence of the fluorescently labeled bovine serum
      albumin could be used for tracing the protein migration and cellular location.
      Further studies suggested that the co-delivery of transcription factor p53 and
      lipophilic drug paclitaxel with the nanocapsules acted synergistically to induce
      Hela cell apoptosis, and the fluorescence of apoptotic cells was clearly observed
      under a fluorescence microscope. Such multifunctional delivery system would have
      great potential applications in drug delivery and theranostic fields. 

PMID- 26203244
TI  - Optimization, ex vivo permeation, and stability study of lipid nanocarrier loaded
      gelatin capsules for treatment of intermittent claudication.
AB  - In this study, an optimized nanodispersible oral dosage form (containing a
      lactate ester) was developed for cilostazol (CZL). CZL is a phosphodiesterase
      inhibitor used for intermittent claudication. We aimed to improve the dissolution
      rate and absorption of CZL giving it a better chance of oral bioavailability, and
      to evaluate its stability on storage. Suitable compositions of nanoemulsion
      preconcentrate formulations were screened via solubility and compatibility tests.
      Response surface methodology and a desirability approach were applied to optimize
      preconcentrates containing minimum amount of surfactant mixture, maximum amount
      of lipid, and possessing the smallest globule size, with the highest
      emulsification and dissolution rates and minimum risk of drug precipitation. As
      part of the optimization process, the main effect, interaction effects and
      quadratic effects of amounts of lipid, and surfactant/co-surfactant ratio on %
      transmittance, globule size, emulsification time, drug precipitation, and drug
      release were investigated. The optimized formulation consisting of 28.9% butyl
      lactate, 28.9% Capryol, 27.82% Solubilisant Gamma 2429, and 14.18% Transcutol
      possessing a globule size of 60 nm was mixed with Aerosil 200. This gave uniform
      free flowing granules, which were characterized for surface and powder
      properties. The self-nanoemulsifying granules (SNEGs) filled into hard gelatin
      capsules showed two- and threefold increase in CZL released compared with
      conventional tablet and pure drug, respectively. The amount of drug permeated
      using non-everted sac technique from the SNEGs was twofold higher than that
      permeated from the tablet suspension. The shelf life was 526 days at 25 degrees
      C. Our study illustrated that the developed SNEGs, with bioenhancing ingredients,
      held great potential as a superior alternative to traditional oral formulations
      of CZL.

PMID- 26203243
TI  - Virosomes of hepatitis B virus envelope L proteins containing doxorubicin:
      synergistic enhancement of human liver-specific antitumor growth activity by
      radiotherapy.
AB  - Bionanocapsules (BNCs) are hollow nanoparticles consisting of hepatitis B virus
      (HBV) envelope L proteins and have been shown to deliver drugs and genes
      specifically to human hepatic tissues by utilizing HBV-derived infection
      machinery. The complex of BNCs with liposomes (LPs), the BNC-LP complexes (a LP
      surrounded by BNCs in a rugged spherical form), could also become active
      targeting nanocarriers by the BNC function. In this study, under acidic
      conditions and high temperature, BNCs were found to fully fuse with LPs (smooth
      surfaced spherical form), deploying L proteins with a membrane topology similar
      to that of BNCs (ie, virosomes displaying L proteins). Doxorubicin (DOX) was
      efficiently encapsulated via the remote loading method at 14.2%+/-1.0% of total
      lipid weight (mean +/- SD, n=3), with a capsule size of 118.2+/-4.7 nm and a zeta
      potential of -51.1+/-1.0 mV (mean +/- SD, n=5). When mammalian cells were exposed
      to the virosomes, the virosomes showed strong cytotoxicity in human hepatic cells
      (target cells of BNCs), but not in human colon cancer cells (nontarget cells of
      BNCs), whereas LPs containing DOX and DOXOVES (structurally stabilized PEGylated
      LPs containing DOX) did not show strong cytotoxicity in either cell type.
      Furthermore, the virosomes preferentially delivered DOX to the nuclei of human
      hepatic cells. Xenograft mice harboring either target or nontarget cell-derived
      tumors were injected twice intravenously with the virosomes containing DOX at a
      low dose (2.3 mg/kg as DOX, 5 days interval). The growth of target cell-derived
      tumors was retarded effectively and specifically. Next, the combination of high
      dose (10.0 mg/kg as DOX, once) with tumor-specific radiotherapy (3 Gy, once after
      2 hours) exhibited the most effective antitumor growth activity in mice harboring
      target cell-derived tumors. These results demonstrated that the HBV-based
      virosomes containing DOX could be an effective antitumor nanomedicine specific to
      human hepatic tissues, especially in combination with radiotherapy. 

PMID- 26203245
TI  - Magnetic resonance-guided regional gene delivery strategy using a tumor stroma
      permeable nanocarrier for pancreatic cancer.
AB  - BACKGROUND: Gene therapy is a very promising technology for treatment of
      pancreatic ductal adenocarcinoma (PDAC). However, its application has been
      limited by the abundant stromal response in the tumor microenvironment. The aim
      of this study was to prepare a dendrimer-based gene-free loading vector with high
      permeability in the tumor stroma and explore an imaging-guided local gene
      delivery strategy for PDAC to promote the efficiency of targeted gene delivery.
      METHODS: The experimental protocol was approved by the animal ethics committee of
      Zhongshan Hospital, Fudan University. Third-generation dendrigraft poly-L-lysines
      was selected as the nanocarrier scaffold, which was modified by cell-penetrating
      peptides and gadolinium (Gd) chelates. DNA plasmids were loaded with these
      nanocarriers via electrostatic interaction. The cellular uptake and loaded gene
      expression were examined in MIA PaCa-2 cell lines in vitro. Permeability of the
      nanoparticles in the tumor stroma and transfected gene distribution in vivo were
      studied using a magnetic resonance imaging-guided delivery strategy in an
      orthotopic nude mouse model of PDAC. RESULTS: The nanocarriers were synthesized
      with a dendrigraft poly-L-lysine to polyethylene glycol to DTPA ratio of
      1:3.4:8.3 and a mean diameter of 110.9+/-7.7 nm. The luciferases were strictly
      expressed in the tumor, and the luminescence intensity in mice treated by Gd
      DPT/plasmid luciferase (1.04*10(4)+/-9.75*10(2) p/s/cm(2)/sr) was significantly
      (P<0.05) higher than in those treated with Gd-DTPA (9.56*10(2)+/-6.15*10
      p/s/cm(2)/sr) and Gd-DP (5.75*10(3)+/- 7.45*10(2) p/s/cm(2)/sr). Permeability of
      the nanoparticles modified by cell-penetrating peptides was superior to that of
      the unmodified counterpart, demonstrating the improved capability of
      nanoparticles for diffusion in tumor stroma on magnetic resonance imaging.
      CONCLUSION: This study demonstrated that an image-guided gene delivery system
      with a stroma-permeable gene vector could be a potential clinically translatable
      gene therapy strategy for PDAC.

PMID- 26203246
TI  - Respiratory syncytial virus-like nanoparticle vaccination induces long-term
      protection without pulmonary disease by modulating cytokines and T-cells
      partially through alveolar macrophages.
AB  - The mechanisms of protection against respiratory syncytial virus (RSV) are poorly
      understood. Virus-like nanoparticles expressing RSV glycoproteins (eg, a
      combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs]) have
      been suggested to be a promising RSV vaccine candidate. To understand the roles
      of alveolar macrophages (AMs) in inducing long-term protection, mice that were 12
      months earlier vaccinated with formalin-inactivated RSV (FI-RSV) or FG VLPs were
      treated with clodronate liposome prior to RSV infection. FI-RSV immune mice with
      clodronate liposome treatment showed increases in eosinophils, plasmacytoid
      dendritic cells, interleukin (IL)-4(+) T-cell infiltration, proinflammatory
      cytokines, chemokines, and, in particular, mucus production upon RSV infection.
      In contrast to FI-RSV immune mice with severe pulmonary histopathology, FG VLP
      immune mice showed no overt sign of histopathology and significantly lower levels
      of eosinophils, T-cell infiltration, and inflammatory cytokines, but higher
      levels of interferon-gamma, which are correlated with protection against RSV
      disease. FG VLP immune mice with depletion of AMs showed increases in
      inflammatory cytokines and chemokines, as well as eosinophils. The results in
      this study suggest that FG nanoparticle vaccination induces long-term protection
      against RSV and that AMs play a role in the RSV protection by modulating
      eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration. 

PMID- 26203248
TI  - Change in prevalence status for children with developmental delay in Taiwan: a
      nationwide population-based retrospective study.
AB  - The purpose of this study was to estimate the prevalence of children aged 0-6
      years with developmental delay (DD) and to examine age-period trends in the
      prevalence of DD diagnosis in Taiwan. For the study population, we selected
      children aged <6 years at baseline (in 1997-2002, N=2,308,790) from the National
      Health Insurance Research Database (a longitudinal database with annual medical
      records of children in Taiwan) to estimate the prevalence of DD. All study
      subjects were followed up until they were 5 years old; the study period was from
      1997 to 2008. The prevalence of DD by year gradually increased from 0.16% to
      3.25% from 1997 to 2008 with an increasing ratio of prevalence of 20% over the 12
      year study period. The prevalence of DD in boys was 2.13 times (2.09-2.18 from
      1997 to 2008) that in girls. The prevalence of DD increased by year of study. The
      effect of sex on the prevalence of DD was significant. Understanding the trend of
      prevalence in the study period and the gap between the rate of early treatment
      and DD prevalence are critical concerns for future research. 

PMID- 26203249
TI  - Differences in maladaptive schemas between patients suffering from chronic and
      acute posttraumatic stress disorder and healthy controls.
AB  - BACKGROUND: War, as a stressor event, has a variety of acute and chronic negative
      consequences, such as posttraumatic stress disorder (PTSD). In this context,
      early maladaptive schema-based problems in PTSD have recently become an important
      research area. The aim of this study was to assess early maladaptive schemas in
      patients with acute and chronic PTSD. METHOD: Using available sampling methods
      and diagnostic criteria, 30 patients with chronic PTSD, 30 patients with acute
      PTSD, and 30 normal military personnel who were matched in terms of age and
      wartime experience were selected and assessed with the Young Schema Questionnaire
      Long Form, Beck Depression Inventory second version (BDI-II), the Beck Anxiety
      Inventory (BAI), and the Impact of Events Scale (IES). RESULTS: Both acute and
      chronic PTSD patients, when compared with normal military personnel, had higher
      scores for all early maladaptive schemas. Additionally, veterans suffering from
      chronic PTSD, as compared with veterans suffering from acute PTSD and veterans
      without PTSD, reported more impaired schemas related, for instance, to Self
      Control, Social Isolation, and Vulnerability to Harm and Illness. DISCUSSION: The
      results of the present study have significant preventative, diagnostic, clinical,
      research, and educational implications with respect to PTSD.

PMID- 26203247
TI  - Shen-Qi-Jie-Yu-Fang has antidepressant effects in a rodent model of postpartum
      depression by regulating the immune organs and subsets of T lymphocytes.
AB  - BACKGROUND: Shen-Qi-Jie-Yu-Fang (SJ Fang) is a herbal preparation used in
      traditional Chinese medicine, and is a potentially important new therapeutic
      agent in postpartum depression (PPD). Previously, we have elucidated the effects
      of SJ Fang on hormone receptors and monoamine neurotransmitters involved in the
      hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes in PPD
      rats. However, the immune-modulating effects of SJ Fang in PPD are still unknown.
      In this study, we explored the effects of SJ Fang on the immune organs and
      subsets of T lymphocytes in PPD rats. METHODS: PPD was created in Sprague-Dawley
      rats by inducing hormone-simulated pregnancy followed by hormone withdrawal.
      After hormone withdrawal, the PPD rats were then treated with fluoxetine at 1, 2,
      and 4 weeks, and the SJ Fang rats were also treated at 1, 2, and 4 weeks.
      Depressive behavior in the rats was evaluated by the forced swim test, sucrose
      consumption test, and open field test. The thymus index and spleen index were
      calculated. Hematoxylin-eosin staining was used to identify pathological features
      in the thymus and spleen. CD3, CD4, and CD8 lymphocyte subsets were analyzed by
      flow cytometry. RESULTS: Both fluoxetine and SJ Fang decreased immobility time,
      increased sucrose consumption, an horizontal and vertical movement. After 4 weeks
      of treatment with fluoxetine or SJ Fang, the thymus index and spleen index were
      significantly higher than at baseline, and the morphology of the thymus and
      spleen were returning to normal. Two weeks after hormone withdrawal, subsets of T
      lymphocytes indicated a shift from immune activation to immune suppression, which
      was reversed by 4 weeks of treatment with fluoxetine or SJ Fang. CONCLUSION: It
      is suggested that T-cell mediate immune responses which may play a role in the
      etiopathology of postpartum depression. SJ Fang had an antidepressant effect on
      the immune system in rats with PPD.

PMID- 26203250
TI  - Relationship between apathy and tumor location, size, and brain edema in patients
      with intracranial meningioma.
AB  - BACKGROUND: The purpose of this study is to assess the relationship between
      apathy and tumor location, size, and brain edema in patients with intracranial
      meningioma. METHODS: We enrolled 65 consecutive patients with meningioma and 31
      normal controls matched for age, gender, and education. The patients were divided
      into frontal or non-frontal (NF) meningioma groups based on magnetic resonance
      imaging; the frontal group was then subdivided to dorsolateral frontal (DLF),
      medial frontal (MF), and ventral frontal (VF) groups. Tumor size and brain edema
      were also recorded. Apathy was assessed by the Apathy Evaluation Scale (AES).
      Assessments were carried out 1 week before and 3 months after surgery,
      respectively. Logistic regression analysis was performed to identify the
      predictive effect of tumor size, location, and brain edema on apathy. Analysis of
      variance and chi-square analysis were applied to compare apathy scores and apathy
      rates among the frontal, NF, and normal control groups, and all subgroups within
      the frontal group. RESULTS: Compared with the NF and control groups, the mean AES
      score was much higher in the frontal group (34.0+/-8.3 versus 28.63+/-6.0,
      P=0.008, and 26.8+/-4.2, P<0.001). Subgroup analysis showed that AES scores in
      the MF group (42.1+/-6.6) and VF group (34.7+/-8.0) were higher than in the DLF
      group (28.5+/-4.36), NF group, and control group (P<0.05). The apathy rate was
      63.6% in the MF group and 25% in the VF group, and significantly higher than in
      the DLF (5.6%), NF (5.3%), and control (0%) groups (P<0.001). A moderate
      correlation was found between AES score and mean diameter of the meningioma in
      all patient groups. Further analysis demonstrated that the correlation existed in
      the DLF (r=0.52, P=0.032), MF (r=0.84, P<0.001), and VF (r=0.64, P=0.008) groups,
      but not in the NF group (r=0.19, P=0.448). The AES score was much higher in
      patients with brain edema than in those without brain edema (34.73+/-8.28 versus
      28.77+/-4.20, t=3.545, P=0.001). In subgroups within frontal meningioma patients,
      the statistical significance above only existed in the MF group (43.50+/-5.26
      versus 25.67+/-6.03, P=0.001). Also, we examined the effect of related factors,
      such as age, sex, education, tumor size, tumor location and edema on the
      occurrence of apathy. The binary logistic regression analysis showed that MF
      [P=0.023, Exp(B) =145.6] and size [P=0.012, Exp(B) =1.20] got into the regression
      equation. Thirty-two patients underwent follow-up post-surgery. A significant
      reduction in AES was found in the MF group (AES1 - AES2 =6.86+/-6.82, t=2.68,
      P=0.04), but not in any of the other groups. CONCLUSION: Apathy occurs frequently
      in patients with frontal meningioma, and is more severe, especially in the MF
      region. Apathy is probably correlated with tumor location and size. Brain edema
      might increase the severity of apathy.

PMID- 26203252
TI  - Attitudes of psychiatrists toward obsessive-compulsive disorder patients.
AB  - PURPOSE: Negative attitudes from doctors and the resulting stigmatization have a
      strong impact on psychiatric patients' poor access to treatment. There are
      various studies centering on doctors' attitudes toward psychiatric patients, but
      rarely focusing on the attitudes to specific disorders, such as obsessive
      compulsive disorder (OCD). This research aimed to focus on psychiatrists'
      attitudes toward OCD patients. PATIENTS AND METHODS: The participants were actual
      psychiatrists who signed a form of consent. The main tool used in this study was
      a questionnaire developed from a focus group interview of ten psychiatrists about
      their attitudes toward OCD patients. RESULTS: More than 80% of the participating
      psychiatrists reported a kindhearted attitude toward OCD patients in the form of
      pity, understanding, and empathy. Approximately one-third of the respondents
      thought that OCD patients talk too much, waste a lot of time, and need more
      patience when compared with other psychiatric disorder sufferers. More than half
      of the respondents thought that OCD patients had poor compliance with behavioral
      therapy. The number of psychiatrists who had confidence in treating OCD patients
      with medications (90.1%) was much higher than those expressing confidence in
      behavioral therapy (51.7%), and approximately 80% perceived that OCD patients
      were difficult to treat. Although 70% of the respondents chose medications
      combined with behavioral therapy as the most preferred mode of treatment, only
      7.7% reported that they were proficient in exposure and response prevention.
      CONCLUSION: Even though most psychiatrists had a more positive than negative
      attitude toward OCD patients, they still thought OCD patients were difficult to
      treat and had poor compliance with behavioral therapy. Only a small number of the
      participating psychiatrists reported proficiency in exposure and response
      prevention.

PMID- 26203251
TI  - Microribonucleic acid dysregulations in children and adolescents with obsessive
      compulsive disorder.
AB  - AIM: Obsessive-compulsive disorder (OCD) is a disorder characterized by the
      presence of obsessions and/or compulsions. Although disorder etiology and
      pathogenesis remains unknown, several theories about OCD development have been
      proposed, and many researchers believe that it is caused by both genetic and
      environmental factors. In the current study, our aim was to investigate miRNA
      levels in OCD. METHODS: In the current study, we evaluated miR18a-5p, miR22-3p,
      miR24-3p, miR106b-5p, miR107, miR125b-5p, and miR155a-5p levels in child and
      adolescent OCD patients. The research sample consisted of a group of 23 OCD
      patients and 40 healthy volunteer controls. RESULTS: There was no significant
      difference in age and sex between the two groups (P>0.05). The levels of miR22
      3p, miR24-3p, miR106b-5p, miR125b-5p, and miR155a-5p were significantly increased
      in the OCD subjects (P<=0.05). There were no statistically significant
      differences in miR18a-5p or miR107 levels between groups (P>=0.05). CONCLUSION:
      There could be a close relationship between levels of circulating miRNAs and OCD.
      If we could understand how the signaling pathways arranged by miRNAs impact on
      central nervous system development, function, and pathology, this understanding
      could improve our knowledge about OCD etiology and treatment.

PMID- 26203253
TI  - Vasopressors in septic shock: a systematic review and network meta-analysis.
AB  - OBJECTIVE: Vasopressor agents are often prescribed in septic shock. However,
      their effects remain controversial. We conducted a systematic review and Bayesian
      network meta-analysis to compare the effects among different types of vasopressor
      agents. DATA SOURCES: We searched for relevant studies in PubMed, Embase, and the
      Cochrane Library databases from database inception until December 2014. STUDY
      SELECTION: Randomized controlled trials in adults with septic shock that
      evaluated different vasopressor agents were selected. DATA EXTRACTION: Two
      authors independently selected studies and extracted data on study
      characteristics, methods, and outcomes. DATA SYNTHESIS: Twenty-one trials
      (n=3,819) met inclusion criteria, which compared eleven vasopressor agents or
      vasopressor combinations (norepinephrine [NE], dopamine [DA], vasopressin [VP],
      epinephrine [EN], terlipressin [TP], phenylephrine [PE], TP+NE, TP + dobutamine
      [DB], NE+DB, NE+EN, and NE + dopexamine [DX]). Except for the superiority of NE
      over DA, the mortality of patients treated with any vasopressor agent or
      vasopressor combination was not significantly different. Compared to DA, NE was
      found to be associated with decreased cardiac adverse events, heart rate
      (standardized mean difference [SMD]: -2.10; 95% confidence interval [CI]: -3.95, 
      0.25; P=0.03), and cardiac index (SMD: -0.73; 95% CI: -1.14, -0.03; P=0.004) and
      increased systemic vascular resistance index (SVRI) (SMD: 1.03; 95% CI: 0.61,
      1.45; P<0.0001). This Bayesian meta-analysis revealed a possible rank of
      probability of mortality among the eleven vasopressor agents or vasopressor
      combinations; from lowest to highest, they are NE+DB, EN, TP, NE+EN, TP+NE, VP,
      TP+DB, NE, PE, NE+DX, and DA. CONCLUSION: In terms of survival, NE may be
      superior to DA. Otherwise, there is insufficient evidence to suggest that any
      other vasopressor agent or vasopressor combination is superior to another. When
      compared to DA, NE is associated with decreased heart rate, cardiac index, and
      cardiovascular adverse events, as well as increased SVRI. The effects of
      vasopressor agents or vasopressor combinations on mortality in patients with
      septic shock require further investigation.

PMID- 26203255
TI  - Supera self-expanding stents for endovascular treatment of femoropopliteal
      disease: a review of the clinical evidence.
AB  - Femoropopliteal lesions account for a significant proportion of endovascular
      interventions for peripheral artery disease in patients with disabling
      claudication or chronic limb ischemia. The femoropopliteal artery crosses two
      joint structures (hip and knee joints) and courses through the muscular adductor
      canal in the thigh, which places the artery at increased biomechanical stress.
      There is a critical need for stent platforms with a reduced risk of stent
      fracture while maintaining patency during long-term follow-up. The Supera
      peripheral stent system has a braided nickel-titanium alloy stent designed to
      withstand the unique stressors along the course of the femoropopliteal artery.
      This design may be associated with improved patency in association with reduced
      stent fracture rates on short- and medium-term follow-up. Further studies,
      including randomized controlled studies, comparing the Supera interwoven nickel
      titanium alloy stent system with other stent platforms and angioplasty alone are
      needed. 

PMID- 26203254
TI  - Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have a long
      history of safe and effective use as both prescription and over-the-counter (OTC)
      analgesics/antipyretics. The mechanism of action of all NSAIDs is through
      reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs)
      including gastrointestinal bleeding as well as cardiovascular and renal effects
      have been reported with NSAID use. In many cases, ADRs may occur because of drug
      drug interactions (DDIs) between the NSAID and a concomitant medication. For
      example, DDIs have been reported when NSAIDs are coadministered with aspirin,
      alcohol, some antihypertensives, antidepressants, and other commonly used
      medications. Because of the pharmacologic nature of these interactions, there is
      a continuum of risk in that the potential for an ADR is dependent on total drug
      exposure. Therefore, consideration of dose and duration of NSAID use, as well as
      the type or class of comedication administered, is important when assessing
      potential risk for ADRs. Safety findings from clinical studies evaluating
      prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health
      care providers can be instrumental in educating patients that using OTC NSAIDs at
      the lowest effective dose for the shortest required duration is vital to
      balancing efficacy and safety. This review discusses some of the most clinically
      relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of
      medication, with a focus on OTC ibuprofen, for which the most data are available.

PMID- 26203256
TI  - Feasibility and safety of rehabilitation after venous thromboembolism.
AB  - BACKGROUND: Venous thromboembolism is a life-threatening disease. In survivors,
      different degrees of functional complaints need to be restored or prevented (eg,
      post-thrombotic syndrome, pulmonary hypertension). Therefore, rehabilitation
      after venous thromboembolism is recommended in Germany. However, a structured
      rehabilitation program has not been defined for this indication. Here, we present
      the experience of a single rehabilitation center. METHODS: Data from consecutive
      pulmonary embolism (PE) patients who were referred for a 3-week inpatient
      rehabilitation program from 2006 to 2014 were retrospectively evaluated. RESULTS:
      In all, 422 patients were identified. The mean age was 63.9+/-13.5 years, the
      mean body mass index (BMI) was 30.6+/-6.2 kg/m2, and 51.9% were female. Deep vein
      thrombosis according to PE was known for 55.5% of all patients. We applied a wide
      range of therapeutic interventions such as bicycle training with monitored heart
      rate in 86.7%, respiratory training in 82.5%, aquatic therapy/swimming in 40.1%,
      and medical training therapy in 14.9% of all patients. Adverse events (AEs)
      occurred in 57 patients during the 3-week rehabilitation period. The most common
      AEs were cold (n=6), diarrhea (n=5), and infection of the upper or lower
      respiratory tract that was treated with antibiotics (n=5). However, three
      patients under anticoagulation therapy suffered from bleeding, which was
      clinically relevant in one. Four patients (0.9%) had to be transferred to a
      primary care hospital for non-PE-associated reasons (acute coronary syndrome,
      pharyngeal abscess, and acute abdominal problems). No influence of any of the
      physical activity interventions on the incidence of any AE was found. CONCLUSION:
      Since PE is a life-threatening disease, it seems reasonable to recommend
      rehabilitation at least in PE patients with an intermediate or high risk. It is
      shown for the first time in this study that a standard rehabilitation program
      after PE is safe. However, efficacy and safety in the long term need to be
      studied prospectively.

PMID- 26203258
TI  - Application of Machine Learning to Development of Copy Number Variation-based
      Prediction of Cancer Risk.
AB  - In the present study, recurrent copy number variations (CNVs) from non-tumor
      blood cell DNAs of Caucasian non-cancer subjects and glioma, myeloma, and
      colorectal cancer-patients, and Korean non-cancer subjects and hepatocellular
      carcinoma, gastric cancer, and colorectal cancer patients, were found to reveal
      for each of the two ethnic cohorts highly significant differences between cancer
      patients and controls with respect to the number of CN-losses and size
      distribution of CN-gains, suggesting the existence of recurrent constitutional
      CNV-features useful for prediction of predisposition to cancer. Upon
      identification by machine learning, such CNV-features could extensively
      discriminate between cancer-patient and control DNAs. When the CNV-features
      selected from a learning-group of Caucasian or Korean mixed DNAs consisting of
      both cancer-patient and control DNAs were employed to make predictions on the
      cancer predisposition of an unseen test group of mixed DNAs, the average
      prediction accuracy was 93.6% for the Caucasian cohort and 86.5% for the Korean
      cohort. 

PMID- 26203259
TI  - Reassessment of the Genome Size in Elaeis guineensis and Elaeis oleifera, and Its
      Interspecific Hybrid.
AB  - Aiming at generating a comprehensive genomic database on Elaeis spp., our group
      is leading several R&D initiatives with Elaeis guineensis (African oil palm) and
      Elaeis oleifera (American oil palm), including the whole-genome sequencing of the
      last. Genome size estimates currently available for this genus are controversial,
      as they indicate that American oil palm genome is about half the size of the
      African oil palm genome and that the genome of the interspecific hybrid is bigger
      than both the parental species genomes. We estimated the genome size of three E.
      guineensis genotypes, five E. oleifera genotypes, and two interspecific hybrids
      genotypes. On average, the genome size of E. guineensis is 4.32 +/- 0.173 pg,
      while that of E. oleifera is 4.43 +/- 0.018 pg. This indicates that both genomes
      are similar in size, even though E. oleifera is in fact bigger. As expected, the
      hybrid genome size is around the average of the two genomes, 4.40 +/- 0.016 pg.
      Additionally, we demonstrate that both species present around 38% of GC content.
      As our results contradict the currently available data on Elaeis spp. genome
      sizes, we propose that the actual genome size of the Elaeis species is around 4
      pg and that American oil palm possesses a larger genome than African oil palm. 

PMID- 26203257
TI  - Preeclampsia: long-term consequences for vascular health.
AB  - Preeclampsia (PE) is a pregnancy-specific syndrome and one of the leading causes
      of preterm birth, neonatal and maternal morbidity and mortality. This disease is
      characterized by new onset hypertension usually in the third trimester of
      pregnancy and is sometimes associated with proteinuria, although proteinuria is
      not a requirement for the diagnosis of PE. In developing countries, women have a
      higher risk of death due to PE than more affluent countries and one of the most
      frequent causes of death is high blood pressure and stroke. Although PE only
      affects approximately 2%-8% of pregnancies worldwide it is associated with severe
      complications such as eclampsia, hemorrhagic stroke, hemolysis, elevated liver
      enzymes and low platelets (HELLP syndrome), renal failure and pulmonary edema.
      Importantly, there is no "cure" for the disease except for early delivery of the
      baby and placenta, leaving PE a health care risk for babies born from PE moms. In
      addition, PE is linked to the development of cardiovascular disease and stroke in
      women after reproductive age, leaving PE a risk factor for long-term health in
      women. This review will highlight factors implicated in the pathophysiology of PE
      that may contribute to long-term effects in women with preeclamptic pregnancies. 

PMID- 26203260
TI  - Significance of downregulation of renal organic cation transporter (SLC47A1) in
      cisplatin-induced proximal tubular injury.
AB  - BACKGROUND/AIM: To elucidate the mechanism responsible for developing acute
      kidney injury in patients with diabetes mellitus, we also evaluated the issue of
      whether advanced glycation endproducts (AGEs) influence the expressions of multi
      antimicrobial extrusion protein (MATE1/SLC47A1) in tubular cells. MATERIALS AND
      METHODS: To detect changing expression of MATE1/SLC47A1 in dose- and time
      dependent manners, human proximal tubular epithelial cells were incubated with
      AGE-aggregated-human serum albumin. As a function assay for MATE1/SLC47A1, human
      proximal tubular epithelial cells were incubated with cisplatin or carboplatin.
      RESULTS: On incubation with AGEs, the expressions of MATE1/SLC47A1 were decreased
      in tubular cells. In addition, the toxicities of cisplatin were increased in
      tubular cells that had been pretreated with AGEs. However, the toxicities of
      carboplatin were smaller than that of cisplatin in proximal tubular epithelial
      cells. CONCLUSION: The expression of the MATE1/SLC47A1 is decreased by AGEs,
      which increases the risk for proximal tubular injury.

PMID- 26203261
TI  - The prognostic significance of protein tyrosine phosphatase 4A2 in breast cancer.
AB  - Although PTP4A3 has been shown to be a very important factor in promoting cancer
      progression, the role of its close family member PTP4A2 is still largely unknown.
      Recent reports have shown contradicting results on the role of PTP4A2 in breast
      cancer progression. Considering this, we aimed to investigate the prognostic
      value of PTP4A2 in five independent breast cancer data sets (minimum 198 patients
      per cohort, totaling 1,124 patients) in the Gene Expression Omnibus Database. We
      found that high expression of PTP4A2 was a favorable prognostic marker in all
      five independent breast cancer data sets, as well as in the combined cohort, with
      a hazard ratio of 0.68 (95% confidence interval =0.56-0.83; P<0.001). Low PTP4A2
      expression was associated with estrogen receptor-negative tumors and tumors with
      higher histological grading; furthermore, low expression was inversely correlated
      with the expression of genes involved in proliferation, including MKI67 and the
      MCM gene family encoding the minichromosome maintenance proteins. These findings
      suggest that PTP4A2 may play a role in breast cancer progression by dysregulating
      cell proliferation. PTP4A2 expression was positively correlated with ESR1, the
      gene encoding estrogen receptor-alpha, and inversely correlated with EGFR
      expression, suggesting that PTP4A2 may be involved in these two important
      oncogenic pathways. Together, our results suggest that expression of PTP4A2 is a
      favorable prognostic marker in breast cancer. 

PMID- 26203262
TI  - A tale of the two PEGylated liposomal doxorubicins.

PMID- 26203263
TI  - B7-H3 silencing by RNAi inhibits tumor progression and enhances chemosensitivity
      in U937 cells.
AB  - BACKGROUND: The role of B7-H3 in acute monocytic leukemia U937 cells has not been
      thoroughly investigated. MATERIALS AND METHODS: B7-H3 knockdown in the U937 cell
      line was performed using small hairpin (sh)RNA lentivirus transduction. The
      effects on cell proliferation, cycle, migration, and invasion were investigated
      by Cell Counting Kit-8 assay, methyl cellulose colony-forming assay, propidium
      iodide staining, and Transwell assays in vitro. Changes in cell growth inhibition
      and apoptosis, when combined with chemotherapy drugs, were determined using the
      Cell Counting Kit-8 and Annexin V-FITC/PI assays. U937 xenograft models were used
      to assess the effects of B7-H3 on tumorigenicity and the therapeutic effect of B7
      H3 knockdown in combination with chemotherapy drugs in vivo. RESULTS:
      Downregulation of B7-H3 significantly decreased U937 cell growth and colony
      forming ability. The mean inhibition rate of tumor growth with B7-H3 knockdown
      was 59.4%, and the expression of both Ki-67 and PCNA in xenografts was
      significantly reduced. After B7-H3 silencing, the U937 cell cycle was arrested at
      the G0/G1 phase. The cell migration rate of B7-H3 knockdown cells was reduced
      more than fivefold, and invasion capacity decreased by 86.7%. B7-H3 RNAi
      profoundly increased the antitumor effect of chemotherapy in vitro and in vivo.
      On day 19, inhibition rates of tumor growth in B7-H3 shRNA combined with
      idarubicin, cytarabine, and idarubicin plus cytarabine were 70.5%, 80.0%, and
      90.0%, respectively (P=0.006, P=0.004, and P=0.016, respectively). CONCLUSION: B7
      H3 may promote U937 cell progression, and shRNA targeting B7-H3 significantly
      enhances sensitivity to chemotherapeutic drugs. These results may provide new
      insight into the function of B7-H3 and a promising therapeutic approach targeting
      B7-H3 in acute monocytic leukemia.

PMID- 26203264
TI  - Single nucleotide polymorphisms of microRNA processing genes and outcome of non
      Hodgkin's lymphoma.
AB  - OBJECTIVE: microRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in
      miRNA-processing machinery genes can affect cancer risk, treatment efficacy, and
      patients' prognosis by mediating the expression of targeted genes. Five miR-SNPs
      in miRNA processing machinery genes, including XPO5 (rs11077), RAN (rs14035),
      TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), in 168 non
      Hodgkin's lymphoma (NHL) patients were evaluated for their association with the
      cancer risk and outcomes associated with NHL. MATERIALS AND METHODS: miR-SNPs
      were genotyped using polymerase chain reaction-ligase detection reaction. The
      survival curves were calculated using the Kaplan-Meier method, and comparisons
      between the curves were made using the log-rank test. Multivariate survival
      analysis was performed using a Cox proportional hazards model. RESULTS: Among the
      five SNPs, only rs197412 located in the coding region of the GEMIN3 gene was
      identified; it was independently associated with overall survival in NHL
      patients, as determined by multivariate analysis (relative risk: 1.649; 95%
      confidence interval: 1.110-2.449; P=0.013). The prognostic value of this miR-SNP
      in patient outcomes was also observed in the diffuse large B-cell lymphoma and T
      cell lymphoma NHL subtypes. CONCLUSION: Our results suggested that the specific
      genetic variants observed in the miRNA machinery genes may affect NHL survival.

PMID- 26203265
TI  - Early childhood wheezers: identifying asthma in later life.
AB  - Wheeze in young children is common, and asthma is the most common noncommunicable
      disease in children. Prevalence studies of recurrent asthma-like symptoms in
      children under the age of 5 years have reported that one third of children in the
      US and Europe are affected, and rates and severity appear to be higher in
      developing countries. Over the last few decades, significant research efforts
      have focused on identification of risk factors and predictors of wheeze and on
      tools to identify which children who wheeze will progress to develop asthma. We
      reviewed the phenotypes of childhood wheezing, genetic risk factors,
      environmental factors, testing/predictive indices, and primary prevention. While
      it is generally agreed that a complex interaction of environmental exposure and
      genetic susceptibility contributes to the development of asthma, limitations in
      predictive tools and tests restrict our ability to provide families with guidance
      as to whether their child with wheeze will ultimately develop asthma. Additional
      research is needed to clarify childhood wheeze phenotypes, to develop tools to
      determine which children will develop asthma, and to determine how and when to
      intervene. If these areas can be addressed, it would help reduce this large
      burden on children, families, and society. 

PMID- 26203266
TI  - Hair restoration surgery: challenges and solutions.
AB  - Hair loss is a common problem affecting both men and women. The most frequent
      etiology is androgenetic alopecia, but other causes of hair loss such as trauma,
      various dermatologic diseases, and systemic diseases can cause alopecia. The loss
      of hair can have profound effects on one's self esteem and emotional well-being,
      as one's appearance plays a role in the work place and interpersonal
      relationships. It is therefore not surprising that means to remedy hair loss are
      widely sought. Hair transplant surgery has become increasingly popular, and the
      results that we are able to create today are quite remarkable, providing a
      natural appearance when the procedure is performed well. In spite of this, hair
      transplant surgery is not perfect. It is not perfect because the hair transplant
      surgeon is still faced with challenges that prevent the achievement of optimal
      results. Some of these challenges include a limit to donor hair availability,
      hair survival, and ways to conceal any evidence of a surgical procedure having
      taken place. This article examines some of the most important challenges facing
      hair restoration surgery today and possible solutions to these challenges. 

PMID- 26203268
TI  - In vitro antioxidant, collagenase inhibition, and in vivo anti-wrinkle effects of
      combined formulation containing Punica granatum, Ginkgo biloba, Ficus carica, and
      Morus alba fruits extract.
AB  - BACKGROUND: In phytotherapy, the therapeutic potential is based on the combined
      action of different herbal drugs. Our objective was to evaluate the antioxidant,
      anti-collagenase (in vitro), and anti-wrinkle (in vivo) effect of combined
      formulation containing Ginkgo biloba, Punica granatum, Ficus carica, and Morus
      alba fruits extract. METHODS: Antioxidant evaluation was based on the scavenging
      activity of free radicals (1,1-diphenyl-2-picrylhydrazyl, H2O2, and O2 (-)) and
      the anti-collagenase activity was based on the reduction of collagenase enzyme in
      vitro. In an in vivo study, 21 female subjects were examined in a placebo
      controlled trail. Facial wrinkle, especially the crow's feet region of eyes, was
      treated with topical formulated 2% cream for 56 days and compared with the
      placebo. RESULTS: In the in vitro study, the combination of fruits extract showed
      a higher antioxidant activity which was comparable with the positive standard
      (ascorbic acid, butylated hydroxyanisole, and Trolox). The data also showed a
      dose-dependent inhibition of collagenase. In the in vivo study, treatment with 2%
      formulated cream for 56 days significantly reduced the percentage of wrinkle
      depth, length, and area with 11.5, 10.07, and 29.55, respectively. CONCLUSION:
      The combined formulation of fruit extracts showed excellent antioxidative and
      anti-collagenase activity as well as a significant effect on anti-wrinkle
      activity on human skin.

PMID- 26203269
TI  - Alcoholic liver disease in Nepal: identifying homemade alcohol as a culprit.
AB  - BACKGROUND: Though the type of alcohol consumed is not thought to be associated
      with alcoholic liver disease (ALD), some studies have shown a beverage-specific
      effect. In the present study, we aim to study the effects of locally brewed
      alcoholic beverages on the development of liver disease. PATIENTS AND METHODS:
      This cross-sectional study was conducted at the internal medicine department of a
      university hospital in Nepal. All patients classified as having either alcohol
      abuse or alcohol dependence by the Diagnostic and Statistical Manual of Mental
      Disorders, 4th Edition were evaluated for the presence of ALD. RESULTS: A total
      of 1,500 patients were screened, of which, 447 patients had ALD. Chronic liver
      disease (CLD) was detected in 144 patients (9.6%). Most of the patients consumed
      homemade locally brewed alcohol. On multivariate analysis, the following
      variables were found to be significantly associated with CLD: male sex (odds
      ratio [OR]: 1.81; 95% confidence interval [CI]: 1.12-2.94; P=0.02): rakshi
      consumption >=30 units (OR: 2.53; 95% CI: 1.07-6.01; P=0.04); and tongba
      consumption (OR: 3.02; 95% CI: 1.22-7.50; P=0.02). CONCLUSION: There was a
      significant increase in the risk of developing ALD with the consumption of rakshi
      and tongba after adjusting for total units consumed. The absence of striking
      differences between our patients with CLD and non-CLD patients with regards to
      the amount of alcohol consumed demonstrates that, although alcohol consumption is
      a prerequisite for the development of ALD, other factors like type of alcoholic
      beverage consumed may be involved.

PMID- 26203270
TI  - Risk factors for recurrent hospital-acquired Clostridium difficile infection in a
      Japanese university hospital.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is a highly prevalent hospital
      associated infection. Although most patients respond well to discontinuation of
      antibiotics, 20%-30% of patients relapse. To initiate early therapeutic measures,
      the risk factors for recurrent CDI must be identified, although very few Japanese
      studies have used standard surveillance definitions to identify these risk
      factors. METHODS: We retrospectively reviewed the medical records of patients
      with health care facility-onset CDI between August 2011 and September 2013.
      Patients with diarrhea who were positive for Clostridium difficile (via an enzyme
      immunoassay) were defined as having CDI. Clinical data (eg, demographics,
      comorbidities, medication, laboratory results, and clinical outcomes) were
      evaluated, and multivariate analysis was used to identify risk factors that were
      associated with recurrent CDI. RESULTS: Seventy-six health care facility-onset
      CDI cases were identified, with an incidence rate of 0.8 cases per 10,000 patient
      days. Fourteen cases (18.4%) were recurrent, with 13 patients having experienced
      a single recurrent episode and one patient having experienced three recurrent
      episodes. The 30-day and 90-day mortality rates were 7.9% and 14.5%,
      respectively. Multivariate analysis revealed that recurrent patients were more
      likely to have underlying malignant disease (odds ratio: 7.98; 95% confidence
      interval: 1.22-52.2; P=0.03) and a history of intensive care unit hospitalization
      (odds ratio: 49.9; 95% confidence interval: 1.01-2,470; P=0.049). CONCLUSION:
      Intensive care unit hospitalization and malignancy are risk factors for recurrent
      CDI. Patients with these factors should be carefully monitored for recurrence and
      provided with appropriate antimicrobial stewardship.

PMID- 26203271
TI  - Implications of compromised zinc status on bone loss associated with chronic
      inflammation in C57BL/6 mice.
AB  - Compromised zinc status and chronic inflammation are independent factors that can
      contribute to bone loss. However, zinc's role in regulating lymphoid and myeloid
      cell populations, combined with the interplay between the immune and skeletal
      systems raises the question as to the extent to which a low-grade inflammatory
      challenge in the context of marginal zinc deficiency would exacerbate bone loss.
      To address this question, young adult C57BL/6 male mice (n=32) were used in a 2*2
      factorial design with dietary zinc (adequate or 35 ppm vs inadequate or -Zn =5
      ppm) and lipopolysaccharide (LPS, 0 or 0.1 mg/kg body weight). Mice were fed
      their respective diets for 10 weeks. On the 6th week, mice had a slow release
      pellet implanted to induce a low-grade inflammation for the final 4 weeks of the
      study. -Zn induced a decrease in total white cell counts and peripheral
      lymphocytes, whereas LPS increased blood monocytes. LPS significantly reduced
      spine bone mineral density and trabecular bone volume and number of the vertebral
      body compared with both zinc adequate and inadequate without LPS groups.
      Likewise, the most pronounced effects on bone strength occurred with LPS,
      however, -Zn also had negative effects on the bone von Mises stresses. LPS
      induced an increase in TNF-alpha and this response was further increased with 
      Zn. Although the marginal zinc deficiency altered immune function, bone loss was
      not exacerbated with low-grade chronic inflammation in marginally zinc-deficient
      young adult mice. These findings demonstrate that in young adult animals an
      immune challenge modestly increases the inflammatory response and worsens bone
      biomechanics in the context of a marginal zinc deficiency, but not to the extent
      that more severe adverse outcomes are observed on bone structural parameters. 

PMID- 26203267
TI  - Linking diet to acne metabolomics, inflammation, and comedogenesis: an update.
AB  - Acne vulgaris, an epidemic inflammatory skin disease of adolescence, is closely
      related to Western diet. Three major food classes that promote acne are: 1)
      hyperglycemic carbohydrates, 2) milk and dairy products, 3) saturated fats
      including trans-fats and deficient omega-3 polyunsaturated fatty acids (PUFAs).
      Diet-induced insulin/insulin-like growth factor (IGF-1)-signaling is superimposed
      on elevated IGF-1 levels during puberty, thereby unmasking the impact of aberrant
      nutrigenomics on sebaceous gland homeostasis. Western diet provides abundant
      branched-chain amino acids (BCAAs), glutamine, and palmitic acid. Insulin and IGF
      1 suppress the activity of the metabolic transcription factor forkhead box O1
      (FoxO1). Insulin, IGF-1, BCAAs, glutamine, and palmitate activate the nutrient
      sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the key
      regulator of anabolism and lipogenesis. FoxO1 is a negative coregulator of
      androgen receptor, peroxisome proliferator-activated receptor-gamma (PPARgamma),
      liver X receptor-alpha, and sterol response element binding protein-1c (SREBP
      1c), crucial transcription factors of sebaceous lipogenesis. mTORC1 stimulates
      the expression of PPARgamma and SREBP-1c, promoting sebum production. SREBP-1c
      upregulates stearoyl-CoA- and Delta6-desaturase, enhancing the proportion of
      monounsaturated fatty acids in sebum triglycerides. Diet-mediated aberrations in
      sebum quantity (hyperseborrhea) and composition (dysseborrhea) promote
      Propionibacterium acnes overgrowth and biofilm formation with overexpression of
      the virulence factor triglyceride lipase increasing follicular levels of free
      palmitate and oleate. Free palmitate functions as a "danger signal," stimulating
      toll-like receptor-2-mediated inflammasome activation with interleukin-1beta
      release, Th17 differentiation, and interleukin-17-mediated keratinocyte
      proliferation. Oleate stimulates P. acnes adhesion, keratinocyte proliferation,
      and comedogenesis via interleukin-1alpha release. Thus, diet-induced metabolomic
      alterations promote the visible sebofollicular inflammasomopathy acne vulgaris.
      Nutrition therapy of acne has to increase FoxO1 and to attenuate mTORC1/SREBP-1c
      signaling. Patients should balance total calorie uptake and restrict refined
      carbohydrates, milk, dairy protein supplements, saturated fats, and trans-fats. A
      paleolithic-like diet enriched in vegetables and fish is recommended. Plant
      derived mTORC1 inhibitors and omega-3-PUFAs are promising dietary supplements
      supporting nutrition therapy of acne vulgaris. 

PMID- 26203272
TI  - Use of localized human growth hormone and testosterone injections in addition to
      manual therapy and exercise for lower back pain: a case series with 12-month
      follow-up.
AB  - OBJECTIVE: The objective of this case series was to investigate the feasibility
      and safety of a novel method for the management of chronic lower back pain.
      Injections of recombinant human growth hormone and testosterone to the painful
      and dysfunctional areas in individuals with chronic lower back pain were used. In
      addition, the participants received manual therapies and exercise addressing
      physical impairments such as motor control, strength, endurance, pain, and loss
      of movement. Pain ratings and self-rated functional outcomes were assessed. STUDY
      DESIGN: This is a case series involving consecutive patients with chronic lower
      back pain who received the intervention of injections of recombinant human growth
      hormone and testosterone, and attended chiropractic and/or physical therapy.
      Outcomes were measured at 12 months from the time of injection. SETTING: A
      community based hospital affiliated office, and a private practice block suite.
      PARTICIPANTS: A total of 60 consecutive patients attending a pain management
      practice for chronic lower back pain were recruited for the experimental
      treatment. Most participants were private pay. INTERVENTIONS: Participants who
      provided informed consent and were determined not to have radicular pain received
      diagnostic blocks. Those who responded favorably to the diagnostic blocks
      received injections of recombinant human growth hormone and testosterone in the
      areas treated with the blocks. Participants also received manipulation- and
      impairment-based exercises. OUTCOME MEASURES: Outcomes were assessed at 12 months
      through pain ratings with the Mankowski Pain Scale and the Oswestry Disability
      Index. RESULTS: Of the 60 patients recruited, 49 provided informed consent, and
      39 completed all aspects of the study. Those patients receiving the intervention
      reported a significant decrease in pain ratings (P<0.01) and a significant
      improvement in self-rated Oswestry Disability Index scores (P<0.01). In addition,
      in the Oswestry Disability Index results, 41% of the patients demonstrated a 50%
      or greater change in their disability score. Of the subjects who withdrew from
      the study, one was due to the pain created by the injections and nine were for
      nonstudy factors. CONCLUSION: The intervention appeared to be safe and the
      results provide a reasonable expectation that the intervention would be
      beneficial for a population of individuals with chronic nonradicular lower back
      pain. Due to the design of the study, causality cannot be inferred, but the
      results do indicate that further study of the intervention may be warranted.

PMID- 26203273
TI  - Pregabalin and placebo responders show different effects on central pain
      processing in chronic pancreatitis patients.
AB  - BACKGROUND: Pain control in chronic pancreatitis is a major challenge; the
      mechanisms behind analgesic treatment are poorly understood. This study aims to
      investigate the differences in pain sensitivity and modulation in chronic
      pancreatitis patients, based on their clinical response (responders vs
      nonresponders) to placebo or pregabalin treatment. METHODS: This study was part
      of a randomized, double-blind, placebo-controlled trial evaluating the analgesic
      effects of pregabalin and placebo in chronic pancreatitis. Post hoc, patients
      were assigned to one of four groups, ie, responders and nonresponders to
      pregabalin (n=16; n=15) or placebo (n=12; n=17) treatment. Responders were
      defined as patients with >30% pain reduction after 3 weeks of treatment. We
      measured change in pain sensitivity before and after the treatment using electric
      pain detection thresholds (ePDT) in dermatomes C5 (generalized effects) and
      Ventral T10 (segmental effects). Descending endogenous pain modulation was
      quantified via conditioned pain modulation (CPM) paradigm. RESULTS: Sixty
      patients were analyzed in a per-protocol analysis. ePDT change in C5 was
      significant vs baseline and greater in pregabalin (1.3 mA) vs placebo responders
      (-0.1 mA; P=0.015). This was not so for ePDT in Ventral T10. CPM increased more
      in pregabalin (9%) vs placebo responders (-17%; P<0.001). CPM changed
      significantly vs baseline only for pregabalin responders (P=0.006). CONCLUSION:
      This hypothesis-generating study provides the first evidence that pain relief
      with pregabalin is associated with anti-hyperalgesic effects and increased
      endogenous inhibitory modulation. No such effects were observed in patients
      experiencing pain relief with the placebo treatment. The mechanisms underlying
      analgesic response to placebo vs drug treatments are different and, together with
      their interactions, deserve further study.

PMID- 26203275
TI  - Importance of perforating vessels in nipple-sparing mastectomy: an anatomical
      description.
AB  - BACKGROUND: Nipple-sparing mastectomy (NSM), understood as an oncologically valid
      procedure, is relatively new, and is an evolution of traditional mastectomy,
      particularly in relation to breast-conserving surgery. The anterior perforating
      branches are responsible for the cutaneous vascularization of the breast skin,
      and their preservation is a fundamental step to avoid possible postoperative
      necrosis. Therefore, evaluating the potential complications of cancer-related
      reconstructive surgical procedures such as NSM, both the distance of the tumoral
      lesion from the skin and the surgical incision site should be carefully
      considered. The preferred site of incision corresponds to the inframammary fold
      or possibly the periareolar area. METHODS: We retrospectively reviewed 113
      patients who underwent NSM from January 2005 to October 2012 to evaluate skin
      complications. The anatomical study was performed by magnetic resonance imaging
      of the breast. RESULTS: Only one of the 113 women who had undergone a NSM
      procedure had total necrosis (0.9%) and six patients had partial necrosis (5.8%)
      of the nipple-areola complex.

PMID- 26203274
TI  - The association between chronic pain and obesity.
AB  - Obesity and pain present serious public health concerns in our society. Evidence
      strongly suggests that comorbid obesity is common in chronic pain conditions, and
      pain complaints are common in obese individuals. In this paper, we review the
      association between obesity and pain in the general population as well as chronic
      pain patients. We also review the relationship between obesity and pain response
      to noxious stimulation in animals and humans. Based upon the existing research,
      we present several potential mechanisms that may link the two phenomena,
      including mechanical/structural factors, chemical mediators, depression, sleep,
      and lifestyle. We discuss the clinical implications of obesity and pain, focusing
      on the effect of weight loss, both surgical and noninvasive, on pain. The
      literature suggests that the two conditions are significant comorbidities,
      adversely impacting each other. The nature of the relationship however is not
      likely to be direct, but many interacting factors appear to contribute. Weight
      loss for obese pain patients appears to be an important aspect of overall pain
      rehabilitation, although more efforts are needed to determine strategies to
      maintain long-term benefit. 

PMID- 26203276
TI  - Identification of genes involved in breast cancer and breast cancer stem cells.
AB  - Breast cancer is the most frequent type of cancer in women. Great progress has
      been made in its treatment but relapse is common. One hypothesis to account for
      the high recurrence rates is the presence of cancer stem cells (CSCs), which have
      the ability to self-renew and differentiate into multiple malignant cell types.
      This study aimed to determine genes that are expressed in breast cancer and
      breast CSCs and to investigate their correlation with stemness. RNA was extracted
      from established breast cancer cell lines and from CSCs derived from five
      different breast cancer patients. DNA microarray analysis was performed and any
      upregulated genes were also studied in other cancer types, including colorectal
      and lung cancer. For genes that were expressed only in breast cancer, knockdown
      based experiments were performed. Finally, the gene expression levels of stemness
      transcription factors were measured. The outcome of the analysis indicated a
      group of genes that were aberrantly expressed mainly in breast cancer cells with
      stemness properties. Knockdown experiments confirmed the impact of several of
      these on NANOG, OCT3/4, and SOX2 transcription factors. It seems that several
      genes that are not directly related with hormone metabolism and basic signal
      transduction pathways might have an important role in relapse and disease
      progression and, thus, can be targeted for new treatment approaches for breast
      cancer. 

PMID- 26203277
TI  - Review of advanced catheter technologies in radiation oncology brachytherapy
      procedures.
AB  - The development of new catheter and applicator technologies in recent years has
      significantly improved treatment accuracy, efficiency, and outcomes in
      brachytherapy. In this paper, we review these advances, focusing on the
      performance of catheter imaging and reconstruction techniques in brachytherapy
      procedures using magnetic resonance images and electromagnetic tracking. The
      accuracy of catheter reconstruction, imaging artifacts, and other notable
      properties of plastic and titanium applicators in gynecologic treatments are
      reviewed. The accuracy, noise performance, and limitations of electromagnetic
      tracking for catheter reconstruction are discussed. Several newly developed
      applicators for accelerated partial breast irradiation and gynecologic treatments
      are also reviewed. New hypofractionated high dose rate treatment schemes in
      prostate cancer and accelerated partial breast irradiation are presented. 

PMID- 26203278
TI  - Population-based study of the association between asthma and pneumococcal disease
      in children.
AB  - BACKGROUND: Although asthma has recently been established as a risk factor for
      pneumococcal disease (PD), few studies have specifically evaluated this
      association in children. METHODS: We conducted a nation-wide population-based
      cohort study of the effect of asthma on childhood PD among all singleton live
      births in Denmark from 1994 to 2007, before the introduction of the 7-valent
      pneumococcal conjugate vaccine. All data were abstracted from Danish medical
      registries. Because underlying comorbidity substantially increases the PD risk in
      children, standard methods were used to assess the evidence of biologic
      interaction between comorbidity and asthma on the risk of PD. RESULTS: There were
      2,253 cases of childhood PD among 888,655 children born in Denmark from 1994 to
      2007. The adjusted incidence rate ratio of the effect of asthma on childhood PD
      was 2.2 (95% confidence interval [CI]: 2.0, 2.5). Age-stratified incidence rate
      ratios were 2.1 (95% CI: 1.8, 2.9) in children 6 months to <24 months, 4.1 (95%
      CI: 3.3, 5.1) in children 24 months to <60 months, and 2.3 (95% CI: 1.6, 3.2) in
      children >=60 months. Evaluation of the biologic interaction between asthma and
      comorbidity in older children revealed that 55% (24 months to <60 months) to 73%
      (>=60 months) of cases among asthma-exposed children can be accounted for by the
      interaction between asthma and comorbidity. CONCLUSION: These results confirm
      that asthma is an important risk factor for PD in children and suggest that
      children with underlying comorbidities are more sensitive to the effect of asthma
      on PD than children without comorbidities.

PMID- 26203279
TI  - Cytotoxicity of a novel nano-silver particle endodontic irrigant.
AB  - PURPOSE: The aim of this study was to evaluate the cytotoxic effect of a novel
      nano-silver particle (25.2+/-6.5 nm) endodontic irrigant (0.2 mM) and compare it
      with 3% sodium hypochlorite. MATERIALS AND METHODS: Two cell types, mouse
      fibroblast National Institutes of Health 3T3 (NIH 3T3) and primary human
      periodontal ligament stem cell (hPDLSCs) were used in a test for the effect of
      direct and indirect (by separating the agent and cell with a layer of agar)
      exposure to the two solutions. In the direct exposure experiment, ten groups of
      cell cultures were exposed to one dilution (3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5,
      1:6 or 1:7) of a nano-silver irrigant for 48 hours; the concentration-response
      function was estimated by determining the number of viable cells in each group by
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The 50%
      lethal dose of the testing irrigant for NIH3T3 and hPDLSCs were estimated. In the
      second part of the experiment, a modified agar overlaying technique was applied.
      Twelve culture wells (6-well plate) were divided into three groups (n=4). The
      cell lysis zone (cytotoxic range) created by the stock nano-silver solution, 3%
      sodium hypochlorite, and an isotonic phosphate buffering saline (control) was
      measured by two double blinded observers (Kappa score =100%). The cytotoxic score
      of specific irrigant was derived by modified Sjogren's method. RESULTS: The 50%
      lethal doses of the testing nano silver irrigant for NIH 3T3 and hPDLSCs after 48
      hours of direct exposure were 0.58 and 0.608 dilution of stock solution,
      respectively. The cytotoxic scores of nano-silver irrigant and control (phosphate
      buffered saline) on NIH 3T3 were 0.25 (95% confidence interval [CI] =0 to 1.04)
      and 0 (95% CI =0 to 0); and on hPDLSCs were 0.13 (95% CI =0 to 0.52) and 0.25
      (95% CI =0 to 1.04), respectively. Toxicity of the test and control group on both
      mouse fibroblasts (P>0.05) and hPDLSCs (P=1.00) was not statistically different.
      CONCLUSION: Our results showed that the nano-silver irrigant was non-cytotoxic to
      both NIH 3T3 and hPDLSCs.

PMID- 26203280
TI  - Papillon-Lefevre syndrome: clinical presentation and management options.
AB  - Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive disorder,
      characterized by diffuse palmoplantar keratoderma and precocious aggressive
      periodontitis, leading to premature loss of deciduous and permanent dentition at
      a very young age. Various etiopathogenic factors are associated with the
      syndrome, like immunologic alterations, genetic mutations, and the role of
      bacteria. Dentists play a significant role in the diagnosis and management of PLS
      as there are characteristic manifestations like periodontal destruction at an
      early age and an early eruption of permanent teeth. Here, we are presenting an
      elaborate review of PLS, its etiopathogenesis, clinical presentation, and
      management options. 

PMID- 26203282
TI  - Predictors of HIV-test utilization in PMTCT among antenatal care attendees in
      government health centers: institution-based cross-sectional study using health
      belief model in Addis Ababa, Ethiopia, 2013.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)/acquired immune deficiency
      syndrome (AIDS) is the most dramatic epidemic of the century that has claimed
      over two decades more than 3 million deaths. Sub-Saharan Africa is heavily
      affected and accounts for nearly 70% of all cases. Mother-to-child transmission
      of HIV is responsible for 20% of all HIV transmissions. With no preventive
      interventions, 50% of HIV infections are transmitted from HIV-positive mothers to
      newborns. HIV-testing is central to prevent vertical transmission. Despite,
      awareness campaigns, prevention measures, and more recently, promotion of
      antiviral regimens, the prevalence of cases and deaths is still rising and the
      prevalence of prevention of mother-to-child transmission (PMTCT) voluntary
      counseling test (VCT) use remains low. This study identifies predictors and
      possible barriers of HIV-testing among antenatal care attendees based on the
      health belief model (HBM) in Addis Ababa, Ethiopia. METHODS: The study was an
      institution-based cross-sectional survey conducted from September 1 to September
      30, 2013. A total of 308 individuals were interviewed using structured
      questionnaires adopted and modified from similar studies. Data were collected
      through face-to-face interviews. A logistic regression was used to identify
      factors associated with HIV-test use. RESULTS: In spite of satisfactory knowledge
      on HIV/AIDS transmission, participants are still at high risk of contracting the
      infection, wherein only 51.8% tested for HIV; among the married, only 84.1% and
      among the gestational age of third trimester, 34.1% mothers tested for HIV. Based
      on the HBM, failure to use PMTCT-HIV-test was related to its perceived lack of
      net benefit (adjusted odds ratio [AOR] =0.34, confidence interval [CI] [0.19
      0.58], P<0.001), but interviewees with high perceived self-efficacy were 1.9
      times more likely to use HIV-test (AOR =1.90, CI [1.09-3.33], P<0.05). CONCLUSION
      AND RECOMMENDATION: This study identifies perceived self-efficacy and perceived
      lack of net benefit as the main predictors of PMTCT-HIV-test use. Hence,
      prevention strategies based on increasing perceived risk, perceived severity, or
      adequate knowledge about HIV/AIDS may not be sufficient to induce PMTCT-HIV-test.
      These data will be useful in designing and improving HIV/AIDS prevention programs
      and focused health communication and counseling strategies in relation to PMTCT
      in Ethiopia.

PMID- 26203281
TI  - Cardiovascular effects of basal insulins.
AB  - Basal insulin is an important component of treatment for both type 1 and type 2
      diabetes. One of the principal aims of treatment in patients with diabetes is the
      prevention of diabetic complications, including cardiovascular disease. There is
      some evidence, although controversial, that attainment of good glycemic control
      reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim
      of this review is to provide an overview of the potential cardiovascular safety
      of the different available preparations of basal insulin. Current basal insulin
      (neutral protamine Hagedorn [NPH], or isophane) and basal insulin analogs
      (glargine, detemir, and the more recent degludec) differ essentially by various
      measures of pharmacokinetic and pharmacodynamic effects in the bloodstream,
      presence and persistence of peak action, and within-subject variability in the
      glucose-lowering response. The currently available data show that basal insulin
      analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1
      and type 2 diabetes, then excluding additional harmful effects on the
      cardiovascular system mediated by activation of the adrenergic system. Given that
      no biological rationale for a possible difference in cardiovascular effect of
      basal insulins has been proposed so far, available meta-analyses of publicly
      disclosed randomized controlled trials do not show any signal of increased risk
      of major cardiovascular events between the different basal insulin analogs.
      However, the number of available cardiovascular events in these trials is very
      small, preventing any clear-cut conclusion. The results of an ongoing clinical
      trial comparing glargine and degludec with regard to cardiovascular safety will
      provide definitive evidence. 

PMID- 26203283
TI  - Influences of peers' and family members' body shapes on perception of body image
      and desire for thinness in Japanese female students.
AB  - PURPOSE: The present study investigated the influence of peers' and family
      members' body shapes on the perception of body image and desire for thinness in
      Japanese female students. METHODS: The study included 342 female, Japanese
      university students between the ages of 18 years and 22 years. They completed an
      anonymous questionnaire, which included questions related to anthropometry and
      body perception. Eating behavior was assessed by the Japanese version of the
      Eating Attitude Test-26. RESULTS: Many students overestimated their body shape
      (81.2% of underweight students and 74.6% of normal students) and had a desire for
      thinness (41.0% of underweight students, 88.2% of normal students, and 100% of
      overweight students). One of the main reasons for the overestimation of their
      body shape was comparison with others. Participants who were interested in a
      friend's body shape were almost three times more likely to have a desire for
      thinness than those who were not interested in a female friend's body shape (odds
      ratio: 3.06, P=0.014). CONCLUSION: The results indicate a possibility that a
      female Japanese student's young female friends' body shapes, influences her
      desire for thinness or her perception of her own body shape.

PMID- 26203284
TI  - Behavioral health screening and intervention for women in Argentina: a
      preliminary model for the childbearing years.
AB  - Untreated behavioral disorders in pregnant women and in women of childbearing age
      pose physical and psychological safety concerns and are barriers to the well
      being of both mother and neonate. The present paper underlines the importance of
      screening in Argentina for behavioral problems in women of childbearing age,
      particularly pregnant women and their newborns. Emphasized is the need to
      formalize this comprehensive screening in a protocol that includes domains of
      mental disorders, behavioral disorders, education, social environment,
      employment, desire for maternity, substance use including non-prescription use of
      prescription medications, eating disorders, suicide risk, interpersonal violence,
      stress, and trauma. Implementation of such a model would require agreement and
      cooperation between the public and private health sectors as well as in the
      development of research for validation of the various screening and interventions
      tools that would be adopted for general use. 

PMID- 26203285
TI  - Increased cesarean section rate in Central Saudi Arabia: a change in practice or
      different maternal characteristics.
AB  - BACKGROUND: Cesarean section (CS) rate has shown an alarming increase. We aimed
      in this work to identify factors contributing to the increasing rate of CS in
      central Saudi Arabia. METHODS: A retrospective cohort study was conducted at King
      Abdulaziz Medical City. Two groups of women were included (G1 and G2). G1 had
      delivered by CS during the year 2002 (CS rate 12%), and G2 had delivered by CS
      during the year 2009 (CS rate 20%). We compared the included women's
      characteristics, neonates, CS indications, and complications. Data were analyzed
      using SPSS version 15 program. Odds ratios and confidence intervals were
      calculated to report precision of categorical data results. A P-value of <=0.05
      was considered significant. RESULTS: A total of 198 women were included in G1 and
      200 in G2. Both groups had comparable maternal and fetal characteristics;
      however, absence of antenatal care has resulted in 70% increase in CS deliveries
      for G2, P=0.008, OR =0.30, CI 0.12-0.76. Previous vaginal surgeries have
      contributed to tenfold increase in CS deliveries for G2, P=0.006, OR =10.37, CI
      1.32-81.78. G2 had eight times increased CS deliveries than G1 due to
      intrauterine growth restriction, P=0.02, OR =8.21, CI 1.02-66.25, and 80%
      increased risk of CS was based on maternal demand, P=0.02, OR =0.20, CI 0.02
      1.71. Decision taken by less-experienced staff was associated with 2.5-fold
      increase in CS deliveries for G2, P=0.002, OR =2.62, CI 1.39-4.93. There was a
      significant increase in CS deliveries under regional analgesia and shorter
      duration of hospital stay for G2, P=0.0001 and P=0.001, respectively. G2 women
      had 2.75-fold increase in neonatal intensive care unit admission, P=0.03, OR
      =2.75, CI 1.06-7.15. CONCLUSION: CS delivery rate significantly increased within
      the studied population. The increased rate of CS may be related to a change in
      physician's practice rather than a change in maternal characteristics, and it
      appears to be reducible.

PMID- 26203286
TI  - Factors associated with successful vaginal birth after cesarean section and
      outcomes in rural area of Anatolia.
AB  - Successful vaginal birth after cesarean section is more comfortable than repeat
      emergency or elective cesarean section. Antenatal examinations are important in
      selection for trial of labor, while birth management can be difficult when the
      patients present at emergency condition. But there is an increased chance of
      vaginal birth with advanced cervical dilation. This study attempts to evaluate
      factors associated with success of vaginal birth after cesarean section and to
      compare the maternal and perinatal outcomes between vaginal birth after cesarean
      section and intrapartum cesarean section in patients who were admitted to
      hospital during the active or second stage of labor. A retrospective evaluation
      was made from the results of 127 patients. Cesarean section was performed in 57
      patients; 70 attempted trial of labor. The factors associated with success of
      vaginal birth after cesarean section were investigated. Maternal and neonatal
      outcomes were compared between the groups. Vaginal birth after cesarean section
      was successful in 55% of cases. Advanced cervical opening, effacement, gravidity,
      parity, and prior vaginal delivery were factors associated with successful
      vaginal birth. The vaginal birth group had more complications (P<0.01), but these
      were minor. The rate of blood transfusion and prevalence of changes in hemoglobin
      level were similar in both groups (P>0.05). In this study, cervical opening,
      effacement, gravidity, parity, and prior vaginal delivery were important factors
      for successful vaginal birth after cesarean section. The patients' requests
      influenced outcome. Trial of labor should take into consideration the patient's
      preference, together with the proper setting. 

PMID- 26203287
TI  - Skull base metastasis from papillary thyroid carcinoma: a report of three cases.
AB  - Skull base metastasis from differentiated thyroid carcinoma, including papillary
      and follicular thyroid carcinoma, is a rare manifestation. Herein, we present
      three cases of skull base metastasis of papillary thyroid carcinoma. The mean age
      of the patients was 68.6 (65-74) years, and the mean interval between initial
      diagnosis and skull base metastasis was 56.3 (28-89) months. Cranial nerve
      palsies were seen in all patients. Intensity modulated radiation therapy to
      deliver 6,000-6,600 cGy to the skull base metastasis was given to all patients,
      in addition to partial resection in one patient. At the time of last follow-up,
      all skull base metastases were well controlled. 

PMID- 26203288
TI  - Erratum: Soya oil-based shampoo superior to 0.5% permethrin lotion for head louse
      infestation [Corrigendum].

PMID- 26203289
TI  - Current perspectives in percutaneous atrial septal defect closure devices.
AB  - In the last decade, percutaneous atrial septal defect (ASD) closure has become
      the treatment of choice in most clinical presentations of ASD. Percutaneous ASD
      closure has established procedural safety through operator experience and
      improved device structure and deliverability. There have also been advances in
      diagnostic capabilities. Devices have evolved from large bulky meshes to
      repositionable, minimal residual mesh content that easily endothelializes and
      conforms well to surrounding structures. Biodegradable technology has been
      introduced and will be closely watched as a future option. The evolution of ASD
      closure device usage in the last four decades incorporates development that
      minimizes a wide range of serious side effects that have been reported over the
      years. Complications reported in the literature include thrombus formation, air
      embolization, device embolization, erosions, residual shunts, and nickel
      hypersensitivity. Modern devices have intermediate to long term data with
      outcomes that have been favorable. Devices are available in multiple sizes with
      improved delivery mechanisms to recapture, reposition, and safely close simple
      and complex ASDs amenable to percutaneous closure. In this review, commonly used
      devices and deployment procedures are discussed together with a look at devices
      that show promise for the future. 

PMID- 26203290
TI  - Overt hepatic encephalopathy in Italy: clinical outcomes and healthcare costs.
AB  - PURPOSE: Hepatic encephalopathy (HE) is a recurrent severe complication of
      progressive hepatic cirrhosis. The aim of this study is to evaluate the average
      annual direct healthcare costs for the treatment of patients with overt HE in
      Italy. PATIENTS AND METHODS: This retrospective, observational study analyzed
      information from the database of ARNO Observatory. Patients with at least one
      hospitalization due to overt HE in the period from January 1, 2011 to December
      31, 2011, were selected and observed during the year following the
      hospitalization. Costs for drugs, diagnostic and therapeutic procedures, and
      hospitalizations were estimated from the Italian National Health Service
      perspective. RESULTS: Out of a population of 2,678,462 subjects, 381 patients
      were identified, of whom, 21.5% died during the first hospitalization and 5.8%
      during the follow-up; the survival rate was 72.7% at the end of the observation
      period. The direct healthcare costs per patient amounted to ?13,393/year (15,295
      USD) (88% for hospitalizations, 8% for drugs, and 4% for diagnostic procedures).
      During the follow-up, 42.5% of patients had at least one rehospitalization due to
      HE. Patients readmitted for HE had an average annual cost of ?21,272 (24,293
      USD), almost doubled if compared to patients without readmissions (?12,098
      [13,816 USD]). CONCLUSION: This analysis showed that patients with HE had
      relevant direct healthcare costs, in which hospitalizations were the most
      important cost drivers.

PMID- 26203291
TI  - Management options in decompensated cirrhosis.
AB  - Chronic injury to the liver from a variety of different sources can result in
      irreversible scarring of the liver, known as cirrhosis. Cirrhosis is a major
      cause of morbidity and mortality in the USA, and according to the Centers for
      Disease Control and Prevention was responsible for 31,903 deaths in 2010 alone.
      It is thus of the utmost importance to appropriately manage these patients in the
      inpatient and outpatient setting to improve morbidity and mortality. In this
      review, we address four major areas of cirrhosis management: outpatient
      management of portal hypertension with decompensation, hepatic encephalopathy,
      hepatorenal syndrome, and bleeding/coagulation issues. Outpatient management
      covers recommendations for health care maintenance and screening. Hepatic
      encephalopathy encompasses a brief review of pathophysiology, treatment in the
      acute setting, and long-term prevention. Hepatorenal syndrome is discussed in
      regards to pathophysiology and treatment in the hospital setting. Finally, a
      discussion of the assessment of coagulation profiles in cirrhosis and
      recommendations for bleeding and thrombosis complications is included. These
      topics are not all encompassing with regard to this complicated population, but
      rather an overview of a few medical problems that are commonly encountered in
      their care. 

PMID- 26203292
TI  - Mild obstructive sleep apnea does not modulate baroreflex sensitivity in adult
      patients.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a chronic and progressive disease.
      OSA is associated with increased cardiovascular morbidity and mortality, the risk
      being more frequently encountered with severe degrees of OSA. Increased
      sympathetic activation and impaired cardiac autonomic control as reflected by
      depressed baroreceptor reflex sensitivity (BRS) are possible mechanisms involved
      in the cardiovascular complications of OSA. However, it is not known at what
      stage of OSA that changes in BRS appear. The aim of this study was to evaluate
      BRS in patients with mild OSA. METHODS: The study population consisted of 81
      overweight patients with mild OSA and 46 body weight-matched non-OSA subjects.
      BRS, apnea-hypopnea index, body mass index, and metabolic parameters were
      assessed. The phenylephrine test was used to measure BRS. RESULTS: Patients in
      the OSA group were slightly but significantly older than the non-OSA population
      (50.3+/-9.3 years vs 45.7+/-11.1 years, P=0.02). Body mass index, percentage body
      fat, blood pressure, fasting glucose, insulin, and lipid levels did not differ
      between the OSA patients and non-OSA subjects. Absolute BRS values in patients
      with mild OSA and non-OSA subjects (9.97+/-6.70 ms/mmHg vs 10.51+/-7.16 ms/mmHg,
      P=0.67) and BRS values proportional to age-related and sex-related reference
      values (91.4%+/-22.7% vs 92.2%+/-21.8%, P=0.84) did not differ from each other.
      BRS <50% of the sex-specific reference value was found in 6% of patients with
      mild OSA and in 2% of non-OSA subjects (P=0.29). CONCLUSION: Patients with mild
      OSA did not show evidence of disturbed BRS in comparison with weight-matched non
      OSA controls.

PMID- 26203293
TI  - Hematopoietic stem cell transplantation in sickle cell disease: patient selection
      and special considerations.
AB  - Hematopoietic stem cell transplantation remains the only curative treatment
      currently in use for patients with sickle cell disease (SCD). The first
      successful hematopoietic stem cell transplantation was performed in 1984. To
      date, approximately 1,200 transplants have been reported. Given the high
      prevalence of this disorder in Africa, and its emergence in the developed world
      through immigration, this number is relatively small. There are many reasons for
      this; primary among them are the availability of a donor, the risks associated
      with this complex procedure, and the cost and availability of resources in the
      developing world. Of these, it is fair to say that the risks associated with the
      procedure have steadily decreased to the point where, if currently performed in a
      center with experience using a matched sibling donor, overall survival is close
      to 100% and event-free survival is over 90%. While there is little controversy
      around offering hematopoietic stem cell transplantation to symptomatic SCD
      patients with a matched sibling donor, there is much debate surrounding the use
      of this modality in "less severe" patients. An overview of the current state of
      our understanding of the pathology and treatment of SCD is important to show that
      our current strategy is not having the desired impact on survival of homozygous
      SCD patients, and should be changed to significantly impact the small proportion
      of these patients who have matched siblings and could be cured, especially those
      without overt clinical manifestations. Both patient families and providers must
      be made to understand the progressive nature of SCD, and should be encouraged to
      screen full siblings of patients with homozygous SCD for their potential to be
      donors. Matched siblings should be referred to an experienced transplant center
      for evaluation and counseling. In this review, we will discuss the rationale for
      these opinions and make recommendations for patient selection. 

PMID- 26203294
TI  - A framework for clinical reasoning in adult cardiology.
AB  - It is well known that an expert clinician formulates a diagnostic hypothesis with
      little clinical data. In comparison, students have difficulties in doing so. The
      mental mechanism of diagnostic reasoning is almost unconscious and therefore
      difficult to teach. The purpose of this essay (devoted to 2nd-year medical
      students) is to present an integrating framework to teach clinical reasoning in
      cardiology. By analyzing cardiology with a synthetic mind, it becomes apparent
      that although there are many diseases, the heart, as an organ, reacts to illness
      with only six basic responses. The clinical manifestations of heart diseases are
      the direct consequence of these cardiac responses. Considering the six cardiac
      responses framework, diagnostic reasoning is done in three overlapping steps.
      With the presented framework, the process of reasoning becomes more visual and
      needs less clinical data, resembling that of the expert clinician. 

PMID- 26203296
TI  - A QTL analysis of host plant effects on fungal endophyte biomass and alkaloid
      expression in perennial ryegrass.
AB  - The association between perennial ryegrass (Loliumperenne L.) and its Epichloe
      fungal endophyte symbiont, Epichloefestucae var. lolii, supports the persistence
      of ryegrass-based pastures principally by producing bioactive alkaloid compounds
      that deter invertebrate herbivory. The host plant genotype affects endophyte
      trait expression, and elucidation of the underlying genetic mechanisms would
      enhance understanding of the symbiosis and support improvement of inplanta
      endophyte performance through plant breeding. Rapid metabolite profiling and
      enzyme-linked immunosorbent assay were used to quantify endophyte alkaloids and
      mycelial mass (MM) in leaves harvested, in consecutive autumns, from an F1
      mapping population hosting standard toxic endophyte. Co-aligned quantitative
      trait loci (QTL) on linkage groups (LG)2, LG4 and LG7 for MM and concentrations
      of alkaloids peramine and ergovaline confirmed host plant effects on both MM and
      alkaloid level and inferred the effect on alkaloids was modulated through the
      quantity of endophyte present in the leaf tissue. For ergovaline, host regulation
      independent of endophyte concentration was also indicated, by the presence of MM
      independent ergovaline QTL on LG4 and LG7. Partitioning of host genetic influence
      between MM-dependent and MM-independent mechanisms was also observed for the
      alkaloid N-formylloline (NFL), in a second mapping population harbouring a tall
      fescue-sourced endophyte. Single-marker analysis on repeated MM and NFL measures
      identified marker-trait associations at nine genome locations, four affecting
      both NFL and MM but five influencing NFL concentration alone. Co-occurrence of
      QTL on LG3, LG4 and LG7 in both mapping populations is evidence for host
      regulatory loci effective across genetic backgrounds and independent of endophyte
      variant. Variation at these loci may be exploited using marker-assisted breeding
      to improve endophyte trait expression in different host population * endophyte
      combinations.

PMID- 26203295
TI  - Altered placental DNA methylation patterns associated with maternal smoking:
      current perspectives.
AB  - The developmental origins of health and disease hypothesis states that adverse
      early life exposures can have lasting, detrimental effects on lifelong health.
      Exposure to maternal cigarette smoking during pregnancy is associated with
      morbidity and mortality in offspring, including increased risks for miscarriage,
      stillbirth, low birth weight, preterm birth, asthma, obesity, altered
      neurobehavior, and other conditions. Maternal cigarette smoking during pregnancy
      interferes with placental growth and functioning, and it has been proposed that
      this may occur through the disruption of normal and necessary placental
      epigenetic patterns. Epigenome-wide association studies have identified a number
      of differentially methylated placental genes that are associated with maternal
      smoking during pregnancy, including RUNX3, PURA, GTF2H2, GCA, GPR135, and HKR1.
      The placental methylation status of RUNX3 and NR3C1 has also been linked to
      adverse infant outcomes, including preterm birth and low birth weight,
      respectively. Candidate gene analyses have also found maternal smoking-associated
      placental methylation differences in the NR3C1, CYP1A1, HTR2A, and HSD11B2 genes,
      as well as in the repetitive elements LINE-1 and AluYb8. The differential
      methylation patterns of several genes have been confirmed to also exhibit altered
      gene expression patterns, including CYP1A1, CYP19A1, NR3C1, and HTR2A. Placental
      methylation patterns associated with maternal smoking during pregnancy may be
      largely gene-specific and tissue-specific and, to a lesser degree, involve global
      changes. It is important for future research to investigate the mechanistic roles
      that these differentially methylated genes may play in mediating the association
      between maternal smoking during pregnancy and disease in later life, as well as
      to elucidate the potential influence of emerging tobacco product use during
      pregnancy, including the use of electronic cigarettes, on placental epigenetics.

PMID- 26203297
TI  - Invisible no more: a scoping review of the health care aide workforce literature.
AB  - BACKGROUND: Healthcare aides (HCAs) are the primary caregivers for vulnerable
      older persons. They have many titles and are largely unregulated, which
      contributes to their relative invisibility. The objective of this scoping review
      was to evaluate the breadth and depth of the HCA workforce literature. METHODS:
      We conducted a search of seven online bibliographic databases. Studies were
      included if published since 1995 in English, peer-reviewed journals. Results were
      iteratively synthesized within and across the following five categories:
      education, supply, use, demand and injury and illness. RESULTS: Of 5,045
      citations screened, 82 studies met inclusion criteria. Few examined HCA
      education; particularly trainee characteristics, program location, length and
      content. Results in supply indicated that the average HCA was female, 36-45 years
      and had an education level of high school or less. Home health HCAs were, on
      average, older and were more likely to be immigrants than those working in other
      settings. The review of studies exploring HCA use revealed that their role was
      unclear - variation in duties, level of autonomy and work setting make describing
      "the" role of an HCA near impossible. Projected increased demand for HCAs and
      high rates of turnover, both at the profession and facility-level, elicit
      predictions of future HCA shortages. Home health HCAs experienced comparatively
      lower job stability, earned less, worked the fewest hours and were less likely to
      have fringe benefits than HCAs employed in hospitals and nursing homes. The
      review of studies related to HCA illness and injury revealed that they were at
      comparatively higher risk of injury than registered nurses and licensed practical
      nurses. CONCLUSIONS: This is the largest, most comprehensive scoping review of
      HCA workforce literature to date. Our results indicate that the HCA workforce is
      both invisible and ubiquitous; as long as this is the case, governments and
      healthcare organizations will be limited in their ability to develop and
      implement feasible, effective HCA workforce plans. The continued undervaluation
      of HCAs adversely impacts care providers, the institutions they work for and
      those who depend on their care. Future workforce planning and research
      necessitates national HCA registries, or at minimum, directories.

PMID- 26203298
TI  - Perianal Crohn's disease and hidradenitis suppurativa: a possible common
      immunological scenario.
AB  - BACKGROUND: Crohn's disease (CD) and Hidradenitis suppurativa (HS) are both
      chronic inflammatory diseases. The pathogenesis of these diseases is
      multifactorial, due to the interaction of genetic and environmental factors
      leading to a deregulated local immune response where T lymphocytes play a major
      role. To the best of our knowledge, no previous study has clarified whether the
      pathogenetic mechanism of perianal CD and HS is the same. We therefore analyzed
      the cellular expression pattern and the cytokine repertoire in three patients
      suffering from both perianal CD and HS. METHODS: We evaluated three patients
      affected by concurrent HS and CD with fistulizing perianal disease. Surgical
      specimens have been fixed and embedded in paraffin prior to sectioning for
      histological examination. Inflammatory tissue curettages have been recovered
      during intervention from perianal fistulas and HS lesions in order to analyze the
      phenotypic and functional characteristics of infiltrating T cells. In particular
      we evaluated T cells, by flow cytometry, for cytokine production profile and
      expression of surface markers. Moreover, analysis of the T cell repertoire was
      performed by means of spectratyping, in only one patient. RESULTS: A higher
      frequency of CD4+ CD161+ T lymphocytes has been detected in CD fistulas and in HS
      lesions than in peripheral blood (PB) samples. In the patient in whom we derived
      enough cells from the three sources, we found higher frequency of CD4+ IL-17-
      producing cells in HS lesion and fistula lesion compared to PB. It is noteworthy
      that the same clonotypes were expanded in this patient in T cells derived from
      both HS lesion and fistula lesion. CONCLUSION: The presence of numerous CD4+
      CD161+ lymphocytes in fistula and HS lesion curettages suggests that these cells
      may play a pathogenic role, and candidates CD161 as a possible biological target
      for medical treatment.

PMID- 26203299
TI  - Interleukin-18 expression increases in response to neurovascular damage following
      soman-induced status epilepticus in rats.
AB  - BACKGROUND: Status epilepticus (SE) can cause neuronal cell death and impaired
      behavioral function. Acute exposure to potent acetylcholinesterase inhibitors
      such as soman (GD) can cause prolonged SE activity, micro-hemorrhage and cell
      death in the hippocampus, thalamus and piriform cortex. Neuroinflammation is a
      prominent feature of brain injury with upregulation of multiple pro-inflammatory
      cytokines including those of the IL-1 family. The highly pleiotropic pro
      inflammatory cytokine interleukin-18 (IL-18) belongs to the IL-1 family of
      cytokines and can propagate neuroinflammation by promoting immune cell
      infiltration, leukocyte and lymphocyte activation, and angiogenesis and helps
      facilitate the transition from the innate to the adaptive immune response. The
      purpose of this study is to characterize the regional and temporal expression of
      IL -18 and related factors in the brain following SE in a rat GD seizure model
      followed by localization of IL-18 to specific cell types. METHODS: The protein
      levels of IL-18, vascular endothelial growth factor and interferon gamma was
      quantified in the lysates of injured brain regions up to 72 h following GD
      induced SE onset using bead multiplex immunoassays. IL-18 was localized to
      various cell types using immunohistochemistry and transmission electron
      microscopy. In addition, macrophage appearance scoring and T-cell quantification
      was determined using immunohistochemistry. Micro-hemorrhages were identified
      using hematoxylin and eosin staining of brain sections. RESULTS: Significant
      increases in IL-18 occurred in the piriform cortex, hippocampus and thalamus
      following SE. IL-18 was primarily expressed by endothelial cells and astrocytes
      associated with the damaged neurovascular unit. The increase in IL-18 was not
      related to macrophage accumulation, neutrophil infiltration or T-cell appearance
      in the injured tissue. CONCLUSIONS: These data show that IL-18 is significantly
      upregulated following GD-induced SE and localized primarily to endothelial cells
      in damaged brain vasculature. IL-18 upregulation occurred following
      leukocyte/lymphocyte infiltration and in the absence of other IL-18-related
      cytokines, suggesting another function, potentially for angiogenesis related to
      GD-induced micro-hemorrhage formation. Further studies at more chronic time
      points may help to elucidate this function.

PMID- 26203300
TI  - Prevalence of type-specific HPV among female university students from northern
      Brazil.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is associated with cervical
      cancer, the most frequent cancer in women from northern Brazil. Assessment of the
      short-term impact of HPV vaccination depends on the availability of data on the
      prevalence of type-specific HPV in young women in the pre-immunization period,
      although these data are currently unavailable for the study region. The aim of
      this study was to estimate the distribution of all mucosal HPV genotypes,
      including low- and high-risk HPV types, in unvaccinated college students from
      northern Brazil. FINDINGS: Specimens were collected from 265 university students
      during routine cervical cancer screening. The HPV DNA was assessed by Polymerase
      Chain Reaction and positive samples were genotyped by Restriction Fragment Length
      Polymorphism. Most students (85.7 %) had normal cytological results. The
      prevalence of HPV was 25.3 % (67/265), with a high frequency of multiple
      infections and non-vaccine high-risk HPV genotypes. The most prevalent type was
      HPV-61 (5.3 %), followed by types 82, 16, 59, and 6. Multiple infections were
      associated with high-risk and possibly high-risk HPVs. CONCLUSIONS: We
      demonstrated a high prevalence of HPV infection in university students from
      northern Brazil. Vaccine high-risk types were relatively rare, emphasizing the
      predominance of carcinogenic genotypes that are not prevented by the currently
      available vaccines. Our study highlights the need to reinforce cytological
      screening in women from northern Brazil, and promote the early diagnosis and
      treatment of the precancerous lesions associated with cervical cancer.

PMID- 26203301
TI  - Expression of a heat-stable NADPH-dependent alcohol dehydrogenase in
      Caldicellulosiruptor bescii results in furan aldehyde detoxification.
AB  - BACKGROUND: Compounds such as furfural and 5-hydroxymethylfurfural (5-HMF) are
      generated through the dehydration of xylose and glucose, respectively, during
      dilute-acid pretreatment of lignocellulosic biomass and are also potent microbial
      growth and fermentation inhibitors. The enzymatic reduction of these furan
      aldehydes to their corresponding, and less toxic, alcohols is an engineering
      approach that has been successfully implemented in both Saccharomyces cerevisiae
      and ethanologenic Escherichia coli, but has not yet been investigated in
      thermophiles relevant to biofuel production through consolidated bioprocessing
      (CBP). Developing CBP-relevant biocatalysts that are either naturally resistant
      to such inhibitors, or are amenable to engineered resistance, is therefore, an
      important component in making biofuels production from lignocellulosic biomass
      feasible. RESULTS: A butanol dehydrogenase encoding gene from Thermoanaerobacter
      pseudethanolicus 39E (Teth39_1597), previously shown to have furfural and 5-HMF
      reducing capabilities, was cloned into a suicide plasmid, pDCW171 and transformed
      into a lactate dehydrogenase mutant of Caldicellulosiruptor bescii. Integration
      of the gene into the C. bescii chromosome was verified via PCR amplification and
      stable expression was observed up to 75 degrees C. Heterologous expression of the
      NADPH-dependent BdhA enzyme conferred increased resistance of the engineered
      strain to both furfural and 5-HMF relative to the wild-type and parental strains.
      Further, when challenged with 15 mM concentrations of either furan aldehyde, the
      ability to eliminate furfural or 5-HMF from the culture medium was significantly
      improved in the engineered strain. CONCLUSIONS: A genetically engineered strain
      of C. bescii (JWCB044) has been constructed that shows both an improved tolerance
      to furan aldehydes and an improved ability to eliminate furfural and 5-HMF from
      the culture medium. The work presented here represents the first example of
      engineering furan aldehyde resistance into a CBP-relevant thermophile and further
      validates C. bescii as being a genetically tractable microbe of importance for
      lignocellulosic biofuel production.

PMID- 26203302
TI  - Prader-Willi syndrome - type 1 deletion, a consequence of an unbalanced
      translocation of chromosomes 13 and 15, easily to be mixed up with a Robertsonian
      translocation.
AB  - BACKGROUND: Prader-Willi syndrome, due to microdeletion of proximal 15q, is a
      well-known cause of syndromic obesity. CASE CHARACTERISTICS: A couple with
      history of repeated first trimester abortions had a son with balanced
      Robertsonian translocation of chromosomes 13 and 15 according to cytogenetic
      banding technique. RESULTS: Chromosomal analysis for the couple was performed. A
      balanced translocation involving BP1-BP3 region of proximal 15q was observed in
      the father. DISCUSSION: Investigations of the parents is mandatory when a
      structural rearrangement is detected in a dysmorphic child.

PMID- 26203303
TI  - A survey of attitudes toward clinical trials and genetic disclosure in autosomal
      dominant Alzheimer's disease.
AB  - INTRODUCTION: Because of its genetic underpinnings and consistent age of onset
      within families, autosomal dominant Alzheimer's disease (ADAD) provides a unique
      opportunity to conduct clinical trials of investigational agents as preventative
      or symptom-delaying treatments. The design of such trials may be complicated by
      low rates of genetic testing and disclosure among persons at risk of inheriting
      disease-causing mutations. METHODS: To better understand the attitudes toward
      genetic testing and clinical trials of persons at risk for ADAD, we surveyed
      participants in the Dominantly Inherited Alzheimer's Network (DIAN), a multisite
      longitudinal study of clinical and biomarker outcomes in ADAD that does not
      require learning genetic status to participate. RESULTS: Eighty participants
      completed a brief anonymous survey by mail or on-line; 40 % reported knowing if
      they carried a gene mutation, 15 % did not know but expressed a desire to learn
      their genetic status, and 45 % did not know and did not desire to know their
      genetic status. Among participants who knew or wished to know their genetic
      status, 86 % were interested in participating in a clinical trial. Seventy-two
      percent of participants who did not wish to learn their genetic status reported
      that they would change their mind, if learning that they carried a mutation gave
      them the opportunity to participate in a clinical trial. Nearly all participants
      responded that they would be interested if an open-label extension were offered.
      CONCLUSIONS: These results suggest that the availability of clinical trials to
      prevent ADAD can affect persons' desire to undergo genetic testing and that
      consideration can be given to performing studies in which such testing is
      required.

PMID- 26203304
TI  - Efforts in favor of health.

PMID- 26203305
TI  - Behavioral, cognitive, and adaptive development in infants with autism spectrum
      disorder in the first 2 years of life.
AB  - BACKGROUND: To delineate the early progression of autism spectrum disorder (ASD)
      symptoms, this study investigated developmental characteristics of infants at
      high familial risk for ASD (HR), and infants at low risk (LR). METHODS:
      Participants included 210 HR and 98 LR infants across 4 sites with comparable
      behavioral data at age 6, 12, and 24 months assessed in the domains of cognitive
      development (Mullen Scales of Early Learning), adaptive skills (Vineland Adaptive
      Behavioral Scales), and early behavioral features of ASD (Autism Observation
      Scale for Infants). Participants evaluated according to the DSM-IV-TR criteria at
      24 months and categorized as ASD-positive or ASD-negative were further stratified
      by empirically derived cutoff scores using the Autism Diagnostic Observation
      Schedule yielding four groups: HR-ASD-High, HR-ASD-Moderate (HR-ASD-Mod), HR-ASD
      Negative (HR-Neg), and LR-ASD-Negative (LR-Neg). RESULTS: The four groups
      demonstrated different developmental trajectories that became increasingly
      distinct from 6 to 24 months across all domains. At 6 months, the HR-ASD-High
      group demonstrated less advanced Gross Motor and Visual Reception skills compared
      with the LR-Neg group. By 12 months, the HR-ASD-High group demonstrated increased
      behavioral features of ASD and decreased cognitive and adaptive functioning
      compared to the HR-Neg and LR-Neg groups. By 24 months, both the HR-ASD-High and
      HR-ASD-Moderate groups demonstrated differences from the LR- and HR-Neg groups in
      all domains. CONCLUSIONS: These findings reveal atypical sensorimotor development
      at 6 months of age which is associated with ASD at 24 months in the most severely
      affected group of infants. Sensorimotor differences precede the unfolding of
      cognitive and adaptive deficits and behavioral features of autism across the 6-
      to 24-month interval. The less severely affected group demonstrates later symptom
      onset, in the second year of life, with initial differences in the social
      communication domain.

PMID- 26203306
TI  - Review of the development of DNA methylation as a marker of response to
      neoadjuvant therapy and outcomes in rectal cancer.
AB  - There is much debate around the preoperative treatment of colorectal cancer and,
      in particular, neoadjuvant chemoradiotherapy in locally advanced rectal cancer.
      This treatment carries a significant risk of harmful side effects and has a
      highly variable response rate. Predictive biomarkers have been the subject of a
      great deal of study with the aim of pretreatment risk stratification in order to
      more accurately determine which patients will derive the most benefit and least
      harm from these treatments. The study of epigenetics in colorectal cancer is
      relatively recent, and distinct patterns of aberrant DNA methylation, in
      particular the cytosine-phosphate-guanine (CpG) island methylator phenotype
      (CIMP), have been demonstrated in colorectal cancer, and their characterisation
      and significance are under debate, particularly in rectal cancer. These patterns
      of DNA methylation have been associated with differences in response to therapy
      and treatment outcomes and therefore have the potential to be used as biomarkers
      in tailored therapy regimes for patients with rectal cancer. This review aims to
      summarise the current state of the art in rectal cancer, with particular regard
      to the determination of DNA methylation patterns, the CpG island methylator
      phenotype and its potential as a novel biomarker in rectal cancer treatment and
      prediction of outcomes and response after neoadjuvant chemoradiotherapy. 

PMID- 26203307
TI  - DNA hypermethylation appears early and shows increased frequency with dysplasia
      in Lynch syndrome-associated colorectal adenomas and carcinomas.
AB  - BACKGROUND: Lynch syndrome (LS) is associated with germline mutations in DNA
      mismatch repair (MMR) genes. The first "hit" to inactivate one allele of the
      predisposing MMR gene is present in every cell, contributing to accelerated
      tumorigenesis. Less information is available of the nature, timing, and order of
      other molecular "hits" required for tumor development. To this end, MMR protein
      expression and coordinated promoter methylation were examined in colorectal
      specimens prospectively collected from LS mutation carriers (n = 55) during
      colonoscopy surveillance (10/2011-5/2013), supplemented with retrospective
      specimens. RESULTS: Loss of MMR protein corresponding to the gene mutated in the
      germline increased with dysplasia, with frequency of 0 % in normal mucosa, 50-68
      % in low-grade dysplasia adenomas, and 100 % in high-grade dysplasia adenomas and
      carcinomas. Promoter methylation as a putative "second hit" occurred in 1/56 (2
      %) of tumors with silenced MMR protein. A general hypermethylation tendency was
      evaluated by two gene sets, eight CpG island methylator phenotype (CIMP) genes,
      and seven candidate tumor suppressor genes linked to colorectal carcinoma (CRC).
      Hypermethylation followed the same trend as MMR protein loss and was present in
      some low-grade dysplasia adenomas that still expressed MMR protein suggesting the
      absence of a "second hit." To assess prospectively collected normal mucosa for
      carcinogenic "fields," the specimen donors were stratified according to age at
      biopsy (50 years or below vs. above 50 years) and further according to the
      absence vs. presence of a (previous or concurrent) diagnosis of CRC. In mutation
      carriers over 50 years old, two markers from the candidate gene panel (SFRP1 and
      SLC5A8) revealed a significantly elevated average degree of methylation in
      individuals with CRC diagnosis vs. those without. CONCLUSIONS: Our findings
      emphasize the importance and early appearance of epigenetic alterations in LS
      associated tumorigenesis. The results serve early detection and assessment of
      progression of CRC.

PMID- 26203308
TI  - A Young Scientists' Perspective on DBS: A Plea for an International DBS
      Organization.
AB  - Our think tank tasked by the Dutch Health Council, consisting of Radboud
      University Nijmegen Honours Academy students with various backgrounds,
      investigated the implications of Deep Brain Stimulation (DBS) for psychiatric
      patients. During this investigation, a number of methodological, ethical and
      societal difficulties were identified. We consider these difficulties to be a
      reflection of a still fragmented field of research that can be overcome with
      improved organization and communication. To this effect, we suggest that it would
      be useful to found a centralized DBS organization. Such an organization makes it
      possible to 1) set up and maintain a repository, 2) facilitate DBS studies with a
      larger sample size, 3) improve communication amongst researchers, clinicians and
      ethical committees, and 4) improve communication between DBS experts and the
      public at large.

PMID- 26203309
TI  - While You Were Sleepwalking: Science and Neurobiology of Sleep Disorders & the
      Enigma of Legal Responsibility of Violence During Parasomnia.
AB  - In terms of medical science and legal responsibility, the sleep disorder category
      of parasomnias, chiefly REM sleep behavior disorder and somnambulism, pose an
      enigmatic dilemma. During an episode of parasomnia, individuals are neither awake
      nor aware, but their actions appear conscious. As these actions move beyond the
      innocuous, such as eating and blurting out embarrassing information, and enter
      the realm of rape and homicide, their degree of importance and relevance
      increases exponentially. Parasomnias that result in illegal activity,
      particularly violence, are puzzling phenomena for medicine and the law. Via a
      review of the pertinent medical literature, a general overview of the current
      scientific knowledge of parasomnias will be provided. Though this knowledge is
      far from complete, it can provide some neurobiological information about the
      nature of parasomnia, including conclusions about a sleepwalker's level of
      intention as well as factors that predispose one to such episodes. Although a
      parasomniac's complete lack of consciousness warrants acquittal from criminal
      liability, it does not exclude responsibility for subjecting oneself to
      exacerbating factors that result in these violent parasomnias. Individuals should
      be held accountable if they could be expected to control these factors. In
      addition, they should undergo appropriate treatment and management in order to
      prevent future parasomnia behaviors. Establishing a legal defense for parasomnia
      will prove difficult due to the strong potential for malingering, so specific
      criteria will be outlined in order to distinguish between true and fraudulent
      claims of crimes committed during parasomniac states.

PMID- 26203310
TI  - Actionable pharmacogenetic markers for prediction and prognosis in breast cancer.
AB  - Breast cancer is a heterogeneous disease that necessitates proper patient
      classification to direct surgery, pharmacotherapy, and radiotherapy. Despite
      patients within the same subgroup receiving similar pharmacotherapy, substantial
      variation in clinical outcomes is observed. Pharmacogenetic variations with
      direct effect on pharmacokinetics and pharmacodynamics play a central role in
      clinical outcomes. Pharmacogenetic markers associated with clinical outcome are
      known as biomarkers. They are termed prognostic biomarkers when their presence is
      associated with a specific clinical outcome. If the presence of such biomarkers
      guides treatment, they are termed predictive biomarkers. A number of
      pharmacogenetic markers have been described in relation to breast cancer
      pharmacotherapy both in the adjuvant and neoadjuvant setting. CYP2D6 allelic
      variants produce variable rates of tamoxifen metabolism and are associated with
      survival outcomes. Other biomarkers have been described in relation to other
      forms of endocrine therapy and trastuzumab. In neoadjuvant and adjuvant breast
      cancer chemotherapy, specific biomarkers were correlated with clinical outcomes
      and risk of drug toxicity. This review highlights key biomarkers in breast cancer
      pharmacotherapy with the potential of translating such study outcomes into
      clinical practice. 

PMID- 26203312
TI  - Is Semantic Processing During Sentence Reading Autonomous or Controlled? Evidence
      from the N400 Component in a Dual Task Paradigm.
AB  - The present study contributes to the discussion on the automaticity of semantic
      processing. Whereas most previous research investigated semantic processing at
      word level, the present study addressed semantic processing during sentence
      reading. A dual task paradigm was combined with the recording of event-related
      brain potentials. Previous research at word level processing reported different
      patterns of interference with the N400 by additional tasks: attenuation of
      amplitude or delay of latency. In the present study, we presented Spanish
      sentences that were semantically correct or contained a semantic violation in a
      critical word. At different intervals preceding the critical word a tone was
      presented that required a high-priority choice response. At short intervals/high
      temporal overlap between the tasks mean amplitude of the N400 was reduced
      relative to long intervals/low temporal overlap, but there were no shifts of peak
      latency. We propose that processing at sentence level exerts a protective effect
      against the additional task. This is in accord with the attentional sensitization
      model (Kiefer & Martens, 2010), which suggests that semantic processing is an
      automatic process that can be enhanced by the currently activated task set. The
      present experimental sentences also induced a P600, which is taken as an index of
      integrative processing. Additional task effects are comparable to those in the
      N400 time window and are briefly discussed. 

PMID- 26203311
TI  - Invisible Stimuli, Implicit Thresholds: Why Invisibility Judgments Cannot be
      Interpreted in Isolation.
AB  - Some studies of unconscious cognition rely on judgments of participants stating
      that they have "not seen" the critical stimulus (e.g., in a masked-priming
      experiment). Trials in which participants gave invisibility judgments are then
      treated as those where the critical stimulus was "subliminal" or "unconscious,"
      as opposed to trials with higher visibility ratings. Sometimes, only these trials
      are further analyzed, for instance, for unconscious priming effects. Here I argue
      that this practice requires implicit assumptions about subjective measures of
      awareness incompatible with basic models of categorization under uncertainty
      (e.g., modern signal-detection and threshold theories). Most importantly, it
      ignores the potential effects of response bias. Instead of taking invisibility
      judgments literally, they would better be employed in parametric experiments
      where stimulus visibility is manipulated systematically, not accidentally. This
      would allow studying qualitative and double dissociations between measures of
      awareness and of stimulus processing per se. 

PMID- 26203313
TI  - Polysaccharide Ecocomposite Materials: Synthesis, Characterization and
      Application for Removal of Pollutants and Bacteria.
AB  - A novel, simple and totally recyclable method has been developed for the
      synthesis of nontoxic, biocompatible and biodegradable composite materials from
      cellulose and chitosan. In this method, [BMIm+Cl-], an ionic liquid (IL), was
      used as a solvent to dissolve and synthesize the [CEL+CS] composite materials.
      Since the IL can be removed from the materials by washing them with water, and
      recovered from the washed solution, the method is totally recyclable. XRD, FTIR,
      NIR and SEM were used to characterize the materials and to confirm that CEL and
      CS were successfully regenerated by the method without any chemical
      transformation. More importantly, we have successfully demonstrated that [CEL+CS]
      material can serve as an effective adsorbent for removal of various endocrine
      disruptors including polychlorophenols and bisphenol A. This is because the
      composites have combined advantages of their components, namely superior chemical
      stability and mechanical stability (from CEL) and excellent adsorption capability
      for pollutants (from CS).

PMID- 26203315
TI  - Protecting Dermatology-Advocating for Our Future.

PMID- 26203314
TI  - Cellulose-Chitosan-Keratin Composite Materials: Synthesis, Immunological and
      Antibacterial Properties.
AB  - Novel composites were synthesized from keratin (KER), cellulose (CEL) and
      chitosan (CS). The method is recyclable because majority (>88%) of [BMIm+Cl-], an
      ionic liquid (IL), used as the sole solvent, was recovered for reuse.
      Experimentally, it was confirmed that unique properties of each component remain
      intact in the composites, namely bactericide (from KER and CS) and anti
      inflammatory property (from KER). Specifically, the composites were examined for
      their anti-inflammatory influence on macrophages. The cells were imaged and
      immunophenotyped to determine the quantity using the macrophage marker CD11b. The
      75:25 [KER+CS] composite was found to have the least amount of CD11b macrophages
      compared to other composites. Bactericidal assays indicated that all composites,
      except the 25:75 [KER+CS], substantially reduce the growth of organisms such as
      vancomycin resistant Enterococcus (VRE) and Eschericia coli. The results clearly
      indicate that the composites possess all properties needed for effective use as a
      wound dressing.

PMID- 26203316
TI  - Psoriasis: The Poster Child for Bench-to-bedside Translational Medicine.
AB  - As the largest and most visible organ, the skin provides opportunities to
      investigate immune responses in clinical studies offering insights that extend
      beyond our protective coat. The interplay between bench-to-bedside approaches are
      complemented by bedside-to-bench exchanges epitomizing translational medicine.
      Conversations beyond improvement in skin lesions that include the impact on
      patients' lives and well-being are also becoming more frequent. Just as advances
      in the realm of cutaneous oncology earned malignant melanoma the title of poster
      child for personalized cancer therapy, new advances involving psoriasis are
      pointing to this moniker in dermatology once again. In this commentary, the
      successful cycle of interactions between psoriasis patients, dermatologists,
      immunologists, and the pharmaceutical industry are highlighted. Lessons learned
      from psoriasis-based studies indicate a bright future for translational medicine
      based in dermatology research labs and clinics. 

PMID- 26203317
TI  - Bimatoprost 0.03% for the Treatment of Eyelash Hypotrichosis: A Pooled Safety
      Analysis of Six Randomized, Double-masked Clinical Trials.
AB  - OBJECTIVE: Describe the safety profile of bimatoprost 0.03% ophthalmic solution
      as once-daily topical treatment for idiopathic or chemotherapy-induced eyelash
      hypotrichosis. DESIGN: Pooled data from six randomized, multicenter, double
      masked, parallel-group clinical studies of at least three-months' duration with
      at least one bimatoprost treatment group. SETTING: Study sites in the United
      States, Canada, United Kingdom, and Japan from 2007 to 2012. PARTICIPANTS: Adults
      with eyelash hypotrichosis, defined as baseline Global Eyelash Assessment of
      minimal or moderate, who received bimatoprost 0.03% (n=680) or vehicle, with no
      prior exposure to bimatoprost (n=379). MEASUREMENTS: Safety assessments included
      adverse events, vital sign measurements, and physical examinations. Common (>=2%)
      and treatment-related adverse events were analyzed at time points up to four
      months and through end of treatment, up to 12 months. RESULTS: Similar overall
      adverse events incidence was reported in bimatoprost and vehicle groups for
      subjects with idiopathic hypotrichosis; a higher incidence in both groups was
      reported for postchemotherapy subjects. Common adverse events included
      conjunctival hyperemia, eyelid pruritus, blepharal pigmentation, nasopharyngitis,
      eyelid erythema, and punctate keratitis. Most adverse events occurred early in
      treatment, were mild in intensity, localized to treatment site, and reversible
      with treatment cessation. Discontinuations due to adverse events were low (3.2%
      for bimatoprost and 2.4% for vehicle). CONCLUSION: Adverse events were consistent
      with the known pharmacologic mechanism of bimatoprost. The safety profile was
      similar across the studies and no new safety signals were observed. Once-daily
      bimatoprost 0.03% for treatment of eyelid hypotrichosis has a favorable safety
      and tolerability profile when applied topically to the upper eyelid margin.

PMID- 26203318
TI  - Clinical Evaluation of a Novel Intense Pulsed Light Source for Facial Skin Hair
      Removal for Home Use.
AB  - OBJECTIVE: The purpose of this Institutional Review Board-approved, open label,
      prospective study was to study the safety and efficacy of a novel pulsed light
      home hair removal device in patients with unwanted facial hair. MATERIALS AND
      METHODS: Seventeen patients were recruited into the clinical trial; two patients
      were lost to follow-up. Patients received six biweekly treatments with the novel
      home-pulsed light device in the facial areas below the level of the cheekbone.
      Follow-up visits were made at one and three months following the last treatment.
      RESULTS: The results showed statistically significant hair reduction numbers
      (22.7 at baseline to 4.4 at the end of the one-month follow-up time period and
      7.0 at the end of the three-month follow-up time period) and percentages of 83.3
      percent at one month post home-pulsed light device treatments and 78.1 percent at
      three months following the novel home-pulsed light device treatments. No adverse
      events with the device in the clinical evaluation were observed. CONCLUSION: This
      novel home use pulsed light device is a safe and effective at-home intense pulsed
      light device for facial hair removal.

PMID- 26203319
TI  - Microneedling Therapy for Atrophic Acne Scars: An Objective Evaluation.
AB  - OBJECTIVE: Treatment of acne scarring is always a challenge. Microneedling
      therapy or percutaneous collagen induction is a new addition to the treatment
      modalities for such scars and has been reported to be simple and effective in
      atrophic acne scar treatment. The aim of this study is to evaluate the clinical
      effect and objectively quantify the histological changes of acne scarring in
      response to skin microneedling. DESIGN: A prospective clinical study.
      PARTICIPANTS: Ten patients with different types of atrophic acne scars were
      subjected to three months of skin microneedling treatment (six sessions at two
      week intervals). MEASUREMENTS: Patients were photographed, and skin biopsies were
      obtained at baseline as well as one and three months from the start of treatment.
      Histometry for epidermal thickness and quantitative evaluation of total elastin;
      newly synthesized tropoelastin; collagen types I, III, and VII; and newly
      synthesized collagen were performed for all biopsies. RESULTS: Compared to the
      baseline, patients' evaluations revealed noticeable clinical improvement in
      atrophic post-acne scars in response to skin microneedling. There was a
      statistically significant increase (p<0.05) in the mean of collagen types I, III,
      and VII and newly synthesized collagen, while total elastin was significantly
      decreased (p<0.05) after the end of treatment. CONCLUSIONS: Multiple minimally
      invasive sessions of skin microneedling are an effective treatment for post-acne
      atrophic scars as it stimulates the repair processes with the advantage of being
      a relatively risk-free, in-office procedure with minimal patient recovery time.

PMID- 26203321
TI  - Management of Periocular Granuloma Annulare Using Topical Dapsone.
AB  - Granuloma annulare is a disease characterized by granulomatous inflammation of
      the dermis. Localized granuloma annulare may resolve spontaneously, while
      generalized granuloma annulare may persist for decades. The authors present the
      case of a 41-year-old Hispanic man with a two-week history of periocular
      granuloma annulare. Due to previously reported success in the use of systemic
      dapsone for the treatment of granuloma annulare, and the periocular proximity of
      the patient's lesion, topical dapsone was used for treatment. Various additional
      therapies for the management of granuloma annulare have been reported, such as
      topical and systemic steroids, isotretinoin, pentoxifylline, cyclosporine,
      Interferon gamma, potassium iodide, nicotinamide, niacinamide, salicylic acid,
      fumaric acid ester, etanercept, infliximab, and hydroxychloroquine. Additional
      clinical trials are necessary to further evaluate the effectiveness of topical
      dapsone in the management of granuloma annulare. 

PMID- 26203320
TI  - Adolescent Scalp Psoriasis: Update on Topical Combination Therapy.
AB  - Plaque psoriasis can begin early in life and negatively affect quality of life.
      Topical agents are generally recommended as first-line therapy for plaque
      psoriasis. The synergy of a vitamin D analog and a steroid in a topical fixed
      combination formulation provides more favorable effectiveness and tolerability as
      compared with either agent alone. The safety and effectiveness of a once-daily
      calcipotriene/betamethasone dipropionate topical suspension have been established
      in children 12 to 17 years of age with scalp plaque psoriasis. Combination
      topical formulations and once-daily dosing decrease regimen complexity and may
      increase adherence. Accommodation of vehicle preference may also improve
      adherence and real-life effectiveness. 

PMID- 26203322
TI  - Cosmetic Warts: Pseudo-Koebnerization of Warts after Cosmetic Procedures for Hair
      Removal.
AB  - OBJECTIVE: To sensitize patients, physicians, and aestheticians about the
      possibility of spread of cutaneous warts during cosmetic procedures, especially
      following temporary hair removal methods, such as shaving, waxing, threading, and
      using depilatory creams, so they practice the requisite safety measures.
      Cutaneous warts caused by human papilloma virus are highly contagious. They tend
      to spread locally with even the trivial trauma of scratching, resulting in
      autoinoculation or "pseudo-Koebnerization." Other than isolated case reports,
      there is a paucity of literature on pseudo-Koebnerization of warts by temporary
      hair removal methods. DESIGN, SETTING, AND PARTICIPANTS: The authors present
      their observations from five patients-two men and three women (Cases 1 to 5)-in
      whom, after a single or a few episodes of a specific temporary hair removal
      method, either pre-existent warts spread locally at a rapid pace or surfaced
      clinically for the first time and then started spreading locally. An attempt was
      made to study the temporal relationship between the cosmetic procedure and the
      eruption or exacerbation of warts. RESULTS: All five cases showed warts in a
      linear or local distribution, suggesting pseudo-Koebnerization and the possible
      use of unclean material used for temporary hair removal methods. One male (Case
      1) and two female (Cases 3 and 4) patients already had pre-existent warts, which
      spread locally following the temporary hair removal procedures. The clinically
      naive other two patients may have acquired human papilloma virus due to cross
      infection from unsterilized razor blades (possibly in Case 2) or from a spouse's
      infected towel pressing against freshly waxed skin (Case 5). Treatment with
      radiofrequency ablation or topical tretinoin was successful in all patients.
      CONCLUSION: Despite the widely prevalent practice of temporary hair removal
      cosmetic procedures around the globe, such pseudo-Koebnerization-induced
      "cosmetic warts" remain under-reported. Through this case series, the authors
      wish to inculcate the practice of more hygienic measures by patients, barbers,
      aestheticians, and beauticians to prevent such cosmetic mishaps.

PMID- 26203323
TI  - Genome sequence of the soil bacterium Corynebacterium callunae type strain DSM
      20147(T).
AB  - Corynebacterium callunae DSM 20147(T) is a member of the genus Corynebacterium
      which contains Gram-positive and non-spore forming bacteria with a high G + C
      content. C. callunae was isolated during a screening for l-glutamic acid
      producing bacteria and belongs to the aerobic and non-haemolytic corynebacteria.
      As this is a type strain in a subgroup of industrial relevant bacteria for many
      of which there are also complete genome sequence available, knowledge of the
      complete genome sequence might enable genome comparisons to identify production
      relevant genetic loci. This project, describing the 2.84 Mbp long chromosome and
      the two plasmids, pCC1 (4.11 kbp) and pCC2 (85.02 kbp), with their 2,647 protein
      coding and 82 RNA genes, will aid the Genomic Encyclopedia of Bacteria and
      Archaea project. 

PMID- 26203324
TI  - Complete genome sequence and description of Salinispira pacifica gen. nov., sp.
      nov., a novel spirochaete isolated form a hypersaline microbial mat.
AB  - During a study of the anaerobic microbial community of a lithifying hypersaline
      microbial mat of Lake 21 on the Kiritimati atoll (Kiribati Republic, Central
      Pacific) strain L21-RPul-D2(T) was isolated. The closest phylogenetic neighbor
      was Spirochaeta africana Z-7692(T) that shared a 16S rRNA gene sequence identity
      value of 90% with the novel strain and thus was only distantly related. A
      comprehensive polyphasic study including determination of the complete genome
      sequence was initiated to characterize the novel isolate. Cells of strain L21
      RPul-D2(T) had a size of 0.2 - 0.25 * 8-9 MUm, were helical, motile, stained Gram
      negative and produced an orange carotenoid-like pigment. Optimal conditions for
      growth were 35 degrees C, a salinity of 50 g/l NaCl and a pH around 7.0.
      Preferred substrates for growth were carbohydrates and a few carboxylic acids.
      The novel strain had an obligate fermentative metabolism and produced ethanol,
      acetate, lactate, hydrogen and carbon dioxide during growth on glucose. Strain
      L21-RPul-D2(T) was aerotolerant, but oxygen did not stimulate growth. Major
      cellular fatty acids were C14:0, iso-C15:0, C16:0 and C18:0. The major polar
      lipids were an unidentified aminolipid, phosphatidylglycerol, an unidentified
      phospholipid and two unidentified glycolipids. Whole-cell hydrolysates contained
      L-ornithine as diagnostic diamino acid of the cell wall peptidoglycan. The
      complete genome sequence was determined and annotated. The genome comprised one
      circular chromosome with a size of 3.78 Mbp that contained 3450 protein-coding
      genes and 50 RNA genes, including 2 operons of ribosomal RNA genes. The DNA G + C
      content was determined from the genome sequence as 51.9 mol%. There were no
      predicted genes encoding cytochromes or enzymes responsible for the biosynthesis
      of respiratory lipoquinones. Based on significant differences to the uncultured
      type species of the genus Spirochaeta, S. plicatilis, as well as to any other
      phylogenetically related cultured species it is suggested to place strain L21
      RPul-D2(T) (=DSM 27196(T) = JCM 18663(T)) in a novel species and genus, for which
      the name Salinispira pacifica gen. nov., sp. nov. is proposed. 

PMID- 26203325
TI  - High quality draft genome sequence and analysis of Pontibacter roseus type strain
      SRC-1(T) (DSM 17521(T)) isolated from muddy waters of a drainage system in
      Chandigarh, India.
AB  - Pontibacter roseus is a member of genus Pontibacter family Cytophagaceae, class
      Cytophagia. While the type species of the genus Pontibacter actiniarum was
      isolated in 2005 from a marine environment, subsequent species of the same genus
      have been found in different types of habitats ranging from seawater, sediment,
      desert soil, rhizosphere, contaminated sites, solar saltern and muddy water. Here
      we describe the features of Pontibacter roseus strain SRC-1(T) along with its
      complete genome sequence and annotation from a culture of DSM 17521(T). The
      4,581,480 bp long draft genome consists of 12 scaffolds with 4,003 protein-coding
      and 50 RNA genes and is a part of Genomic Encyclopedia of Type Strains: KMG-I
      project. 

PMID- 26203326
TI  - Draft genome sequences for the obligate bacterial predators Bacteriovorax spp. of
      four phylogenetic clusters.
AB  - Bacteriovorax is the halophilic genus of the obligate bacterial predators,
      Bdellovibrio and like organisms. The predators are known for their unique
      biphasic life style in which they search for and attack their prey in the free
      living phase; penetrate, grow, multiply and lyse the prey in the intraperiplasmic
      phase. Bacteriovorax isolates representing four phylogenetic clusters were
      selected for genomic sequencing. Only one type strain genome has been published
      so far from the genus Bacteriovorax. We report the genomes from non-type strains
      isolated from aquatic environments. Here we describe and compare the genomic
      features of the four strains, together with the classification and annotation. 

PMID- 26203327
TI  - High-quality permanent draft genome sequence of the Parapiptadenia rigida
      nodulating Cupriavidus sp. strain UYPR2.512.
AB  - Cupriavidus sp. strain UYPR2.512 is an aerobic, motile, Gram-negative, non-spore
      forming rod that was isolated from a root nodule of Parapiptadenia rigida grown
      in soils from a native forest of Uruguay. Here we describe the features of
      Cupriavidus sp. strain UYPR2.512, together with sequence and annotation. The
      7,858,949 bp high-quality permanent draft genome is arranged in 365 scaffolds of
      369 contigs, contains 7,411 protein-coding genes and 76 RNA-only encoding genes,
      and is part of the GEBA-RNB project proposal. 

PMID- 26203328
TI  - Draft genome sequence and characterization of Desulfitobacterium hafniense PCE-S.
AB  - This genome report describes the draft genome and the physiological
      characteristics of Desulfitobacterium hafniense PCE-S, a Gram-positive bacterium
      known to dechlorinate tetrachloroethene (PCE) to dichloroethene by a PCE
      reductive dehalogenase. The draft genome has a size of 5,666,696 bp with a G + C
      content of 47.3%. The genome is very similar to the already sequenced
      Desulfitobacterium hafniense Y51 and the type strain DCB-2. We identified two
      complete reductive dehalogenase (rdh) genes in the genome of D. hafniense PCE-S,
      one of which encodes PceA, the PCE reductive dehalogenase, and is located on a
      transposon. Interestingly, this transposon structure differs from the PceA
      containing transposon of D. hafniense Y51. The second rdh encodes an unknown
      reductive dehalogenase, highly similar to rdhA 7 found in D. hafniense DCB-2, in
      which the corresponding gene is disrupted. This reductive dehalogenase might be
      responsible for the reductive dechlorination of 2,4,5-trichlorophenol and
      pentachlorophenol, which is mediated by D. hafniense PCE-S in addition to the
      reductive dechlorination of PCE. 

PMID- 26203329
TI  - High quality draft genome of Lactobacillus kunkeei EFB6, isolated from a German
      European foulbrood outbreak of honeybees.
AB  - The lactic acid bacterium Lactobacillus kunkeei has been described as an
      inhabitant of fructose-rich niches. Here we report on the genome sequence of L.
      kunkeei EFB6, which has been isolated from a honeybee larva infected with
      European foulbrood. The draft genome comprises 1,566,851 bp and 1,417 predicted
      protein-encoding genes. 

PMID- 26203330
TI  - Genome sequence of the Roseovarius mucosus type strain (DSM 17069(T)), a
      bacteriochlorophyll a-containing representative of the marine Roseobacter group
      isolated from the dinoflagellate Alexandrium ostenfeldii.
AB  - Roseovarius mucosus Biebl et al. 2005 is a bacteriochlorophyll a-producing
      representative of the marine Roseobacter group within the alphaproteobacterial
      family Rhodobacteraceae, which was isolated from the dinoflagellate Alexandrium
      ostenfeldii. The marine Roseobacter group was found to be abundant in the ocean
      and plays an important role for global and biogeochemical processes. Here we
      describe the features of the R. mucosus strain DFL-24(T) together with its genome
      sequence and annotation generated from a culture of DSM 17069(T). The 4,247,724
      bp containing genome sequence encodes 4,194 protein-coding genes and 57 RNA
      genes. In addition to the presence of four plasmids, genome analysis revealed the
      presence of genes associated with host colonization, DMSP utilization,
      cytotoxins, and quorum sensing that could play a role in the interrelationship of
      R. mucosus with the dinoflagellate A. ostenfeldii and other marine organisms.
      Furthermore, the genome encodes genes associated with mixotrophic growth, where
      both reduced inorganic compounds for lithotrophic growth and a photoheterotrophic
      lifestyle using light as additional energy source could be used. 

PMID- 26203331
TI  - Large-scale contamination of microbial isolate genomes by Illumina PhiX control.
AB  - With the rapid growth and development of sequencing technologies, genomes have
      become the new go-to for exploring solutions to some of the world's biggest
      challenges such as searching for alternative energy sources and exploration of
      genomic dark matter. However, progress in sequencing has been accompanied by its
      share of errors that can occur during template or library preparation,
      sequencing, imaging or data analysis. In this study we screened over 18,000
      publicly available microbial isolate genome sequences in the Integrated Microbial
      Genomes database and identified more than 1000 genomes that are contaminated with
      PhiX, a control frequently used during Illumina sequencing runs. Approximately
      10% of these genomes have been published in literature and 129 contaminated
      genomes were sequenced under the Human Microbiome Project. Raw sequence reads are
      prone to contamination from various sources and are usually eliminated during
      downstream quality control steps. Detection of PhiX contaminated genomes
      indicates a lapse in either the application or effectiveness of proper quality
      control measures. The presence of PhiX contamination in several publicly
      available isolate genomes can result in additional errors when such data are used
      in comparative genomics analyses. Such contamination of public databases have far
      reaching consequences in the form of erroneous data interpretation and analyses,
      and necessitates better measures to proofread raw sequences before releasing them
      to the broader scientific community. 

PMID- 26203332
TI  - Marine microbial biodiversity, bioinformatics and biotechnology (M2B3) data
      reporting and service standards.
AB  - Contextual data collected concurrently with molecular samples are critical to the
      use of metagenomics in the fields of marine biodiversity, bioinformatics and
      biotechnology. We present here Marine Microbial Biodiversity, Bioinformatics and
      Biotechnology (M2B3) standards for "Reporting" and "Serving" data. The M2B3
      Reporting Standard (1) describes minimal mandatory and recommended contextual
      information for a marine microbial sample obtained in the epipelagic zone, (2)
      includes meaningful information for researchers in the oceanographic,
      biodiversity and molecular disciplines, and (3) can easily be adopted by any
      marine laboratory with minimum sampling resources. The M2B3 Service Standard
      defines a software interface through which these data can be discovered and
      explored in data repositories. The M2B3 Standards were developed by the European
      project Micro B3, funded under 7(th) Framework Programme "Ocean of Tomorrow", and
      were first used with the Ocean Sampling Day initiative. We believe that these
      standards have value in broader marine science. 

PMID- 26203333
TI  - High quality draft genome sequence of Leucobacter chironomi strain MM2LB(T) (DSM
      19883(T)) isolated from a Chironomus sp. egg mass.
AB  - Leucobacter chironomi strain MM2LB(T) (Halpern et al., Int J Syst Evol Microbiol
      59:665-70 2009) is a Gram-positive, rod shaped, non-motile, aerobic,
      chemoorganotroph bacterium. L. chironomi belongs to the family Microbacteriaceae,
      a family within the class Actinobacteria. Strain MM2LB(T) was isolated from a
      chironomid (Diptera; Chironomidae) egg mass that was sampled from a waste
      stabilization pond in northern Israel. In a phylogenetic tree based on 16S rRNA
      gene sequences, strain MM2LB(T) formed a distinct branch within the radiation
      encompassing the genus Leucobacter. Here we describe the features of this
      organism, together with the complete genome sequence and annotation. The DNA GC
      content is 69.90%. The chromosome length is 2,964,712 bp. It encodes 2,690
      proteins and 61 RNA genes. L. chironomi genome is part of the Genomic
      Encyclopedia of Type Strains, Phase I: the one thousand microbial genomes (KMG)
      project. 

PMID- 26203334
TI  - Complete genome sequence of endophytic nitrogen-fixing Klebsiella variicola
      strain DX120E.
AB  - Klebsiella variicola strain DX120E (=CGMCC 1.14935) is an endophytic nitrogen
      fixing bacterium isolated from sugarcane crops grown in Guangxi, China and
      promotes sugarcane growth. Here we summarize the features of the strain DX120E
      and describe its complete genome sequence. The genome contains one circular
      chromosome and two plasmids, and contains 5,718,434 nucleotides with 57.1% GC
      content, 5,172 protein-coding genes, 25 rRNA genes, 87 tRNA genes, 7 ncRNA genes,
      25 pseudo genes, and 2 CRISPR repeats. 

PMID- 26203335
TI  - High quality draft genome sequence of Meganema perideroedes str. Gr1(T) and a
      proposal for its reclassification to the family Meganemaceae fam. nov.
AB  - Meganema perideroedes Gr1(T) is a filamentous bacterium isolated from an
      activated sludge wastewater treatment plant where it is implicated in poor sludge
      settleability (bulking). M. perideroedes is the sole described species of the
      genus Meganema and of the proposed novel family "Meganemaceae". Here we describe
      the features of the type strain Gr1(T) along with its annotated genome sequence.
      The 3,409,949 bp long draft genome consists of 22 scaffolds with 3,033 protein
      coding and 59 RNA genes and is a part of Genomic Encyclopedia of Type Strains,
      Phase I: the one thousand microbial genomes KMG project. Notably, genome
      annotation indicated the potential for facultative methylotrophy. However, the
      ability to utilize methanol as a carbon source could not be empirically
      demonstrated for the type strain or for in situ Meganema spp. strains. 

PMID- 26203336
TI  - High-quality permanent draft genome sequence of Bradyrhizobium sp. Th.b2, a
      microsymbiont of Amphicarpaea bracteata collected in Johnson City, New York.
AB  - Bradyrhizobium sp. Th.b2 is an aerobic, motile, Gram-negative, non-spore-forming
      rod that was isolated from an effective nitrogen-fixing root nodule of
      Amphicarpaea bracteata collected in Johnson City, New York. Here we describe the
      features of Bradyrhizobium sp. Th.b2, together with high-quality permanent draft
      genome sequence information and annotation. The 10,118,060 high-quality draft
      genome is arranged in 266 scaffolds of 274 contigs, contains 9,809 protein-coding
      genes and 108 RNA-only encoding genes. This rhizobial genome was sequenced as
      part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and
      Archaea-Root Nodule Bacteria (GEBA-RNB) project. 

PMID- 26203337
TI  - Genomic Encyclopedia of Bacterial and Archaeal Type Strains, Phase III: the
      genomes of soil and plant-associated and newly described type strains.
AB  - The Genomic Encyclopedia of Bacteria and Archaea (GEBA) project was launched by
      the JGI in 2007 as a pilot project to sequence about 250 bacterial and archaeal
      genomes of elevated phylogenetic diversity. Herein, we propose to extend this
      approach to type strains of prokaryotes associated with soil or plants and their
      close relatives as well as type strains from newly described species.
      Understanding the microbiology of soil and plants is critical to many DOE mission
      areas, such as biofuel production from biomass, biogeochemistry, and carbon
      cycling. We are also targeting type strains of novel species while they are being
      described. Since 2006, about 630 new species have been described per year, many
      of which are closely aligned to DOE areas of interest in soil, agriculture,
      degradation of pollutants, biofuel production, biogeochemical transformation, and
      biodiversity. 

PMID- 26203338
TI  - High-quality permanent draft genome sequence of Bradyrhizobium sp. Tv2a.2, a
      microsymbiont of Tachigali versicolor discovered in Barro Colorado Island of
      Panama.
AB  - Bradyrhizobiumsp. Tv2a.2 is an aerobic, motile, Gram-negative, non-spore-forming
      rod that was isolated from an effective nitrogen-fixing root nodule of Tachigali
      versicolor collected in Barro Colorado Island of Panama. Here we describe the
      features of Bradyrhizobiumsp. Tv2a.2, together with high-quality permanent draft
      genome sequence information and annotation. The 8,496,279 bp high-quality draft
      genome is arranged in 87 scaffolds of 87 contigs, contains 8,109 protein-coding
      genes and 72 RNA-only encoding genes. This rhizobial genome was sequenced as part
      of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and
      Archaea-Root Nodule Bacteria (GEBA-RNB) project. 

PMID- 26203339
TI  - Draft genome of Myxosarcina sp. strain GI1, a baeocytous cyanobacterium
      associated with the marine sponge Terpios hoshinota.
AB  - To date, genome sequences (complete or in draft form) from only six baeocytous
      cyanobacteria in four genera have been reported: Xenococcus, Chroococcidiopsis,
      Pleurocapsa, and Stanieria. To expand our knowledge on the diversity of
      baeocytous cyanobacteria, this study sequenced the genome of GI1, which is a
      Myxosarcina-like baeocytous cyanobacterium. GI1 is of interest not only because
      of its phylogenetic niche, but also because it is a cyanobiont isolated from the
      marine cyanobacteriosponge Terpios hoshinota, which has been shown to cause the
      death of corals. The ~7 Mb draft GI1 genome contains 6,891 protein-coding genes
      and 62 RNA genes. A comparison of genomes among the sequenced baeocytous
      cyanobacterial strains revealed the existence or absence of numerous discrete
      genes involved in nitrogen metabolism. It will be interesting to determine
      whether these genes are important for cyanobacterial adaptations and interactions
      between cyanobionts and their marine sponge hosts. 

PMID- 26203340
TI  - High quality draft genome sequence of Brachymonas chironomi AIMA4(T) (DSM
      19884(T)) isolated from a Chironomus sp. egg mass.
AB  - Brachymonas chironomi strain AIMA4(T) (Halpern et al., 2009) is a Gram-negative,
      non-motile, aerobic, chemoorganotroph bacterium. B. chironomi is a member of the
      Comamonadaceae, a family within the class Betaproteobacteria. This species was
      isolated from a chironomid (Diptera; Chironomidae) egg mass, sampled from a waste
      stabilization pond in northern Israel. Phylogenetic analysis based on the 16S
      rRNA gene sequences placed strain AIMA4(T) in the genus Brachymonas. Here we
      describe the features of this organism, together with the complete genome
      sequence and annotation. The DNA GC content is 63.5%. The chromosome length is
      2,509,395 bp. It encodes 2,382 proteins and 68 RNA genes. Brachymonas chironomi
      genome is part of the Genomic Encyclopedia of Type Strains, Phase I: the one
      thousand microbial genomes (KMG) project. 

PMID- 26203341
TI  - Complete genome sequence of Salmonella enterica subspecies arizonae str. RKS2983.
AB  - Salmonella arizonae (also called Salmonella subgroup IIIa) is a Gram-negative,
      non-spore-forming, motile, rod-shaped, facultatively anaerobic bacterium. S.
      arizonae strain RKS2983 was isolated from a human in California, USA. S. arizonae
      lies somewhere between Salmonella subgroups I (human pathogens) and V (also
      called S. bongori; usually non-pathogenic to humans) and so is an ideal model
      organism for studies of bacterial evolution from non-human pathogen to human
      pathogens. We hence sequenced the genome of RKS2983 for clues of genomic events
      that might have led to the divergence and speciation of Salmonella into distinct
      lineages with diverse host ranges and pathogenic features. The 4,574,836 bp
      complete genome contains 4,203 protein-coding genes, 82 tRNA genes and 7 rRNA
      operons. This genome contains several characteristics not reported to date in
      Salmonella subgroup I or V and may provide information about the genetic
      divergence of Salmonella pathogens. 

PMID- 26203342
TI  - High-quality permanent draft genome sequence of the Parapiptadenia rigida
      nodulating Burkholderia sp. strain UYPR1.413.
AB  - Burkholderia sp. strain UYPR1.413 is an aerobic, motile, Gram-negative, non-spore
      forming rod that was isolated from a root nodule of Parapiptadenia rigida
      collected at the Angico plantation, Mandiyu, Uruguay, in December 2006. A survey
      of symbionts of P. rigida in Uruguay demonstrated that this species is nodulated
      predominantly by Burkholderia microsymbionts. Moreover, Burkholderia sp. strain
      UYPR1.413 is a highly efficient nitrogen fixing symbiont with this host.
      Currently, the only other sequenced isolate to fix with this host is Cupriavidus
      sp. UYPR2.512. Therefore, Burkholderia sp. strain UYPR1.413 was selected for
      sequencing on the basis of its environmental and agricultural relevance to issues
      in global carbon cycling, alternative energy production, and biogeochemical
      importance, and is part of the GEBA-RNB project. Here we describe the features of
      Burkholderia sp. strain UYPR1.413, together with sequence and annotation. The
      10,373,764 bp high-quality permanent draft genome is arranged in 336 scaffolds of
      342 contigs, contains 9759 protein-coding genes and 77 RNA-only encoding genes. 

PMID- 26203343
TI  - Complete genome sequence of Actinobacillus equuli subspecies equuli ATCC
      19392(T).
AB  - Actinobacillus equuli subsp. equuli is a member of the family Pasteurellaceae
      that is a common resident of the oral cavity and alimentary tract of healthy
      horses. At the same time, it can also cause a fatal septicemia in foals, commonly
      known as sleepy foal disease or joint ill disease. In addition, A. equuli subsp.
      equuli has recently been reported to act as a primary pathogen in breeding sows
      and piglets. To better understand how A. equuli subsp. equuli can cause disease,
      the genome of the type strain of A. equuli subsp. equuli, ATCC 19392(T), was
      sequenced using the PacBio RSII sequencing system. Its genome is comprised of
      2,431,533 bp and is predicted to encode 2,264 proteins and 82 RNAs. 

PMID- 26203345
TI  - Characterization of nonlinear ultrasound fields of 2D therapeutic arrays.
AB  - A current trend in high intensity focused ultrasound (HIFU) technologies is to
      use 2D focused phased arrays that enable electronic steering of the focus,
      beamforming to avoid overheating of obstacles (such as ribs), and better focusing
      through inhomogeneities of soft tissue using time reversal methods. In many HIFU
      applications, the acoustic intensity in situ can reach thousands of W/cm2 leading
      to nonlinear propagation effects. At high power outputs, shock fronts develop in
      the focal region and significantly alter the bioeffects induced. Clinical
      applications of HIFU are relatively new and challenges remain for ensuring their
      safety and efficacy. A key component of these challenges is the lack of standard
      procedures for characterizing nonlinear HIFU fields under operating conditions.
      Methods that combine low-amplitude pressure measurements and nonlinear modeling
      of the pressure field have been proposed for axially symmetric single element
      transducers but have not yet been validated for the much more complex 3D fields
      generated by therapeutic arrays. Here, the method was tested for a clinical HIFU
      source comprising a 256-element transducer array. A numerical algorithm based on
      the Westervelt equation was used to enable 3D full-diffraction nonlinear
      modeling. With the acoustic holography method, the magnitude and phase of the
      acoustic field were measured at a low power output and used to determine the
      pattern of vibrations at the surface of the array. This pattern was then scaled
      to simulate a range of intensity levels near the elements up to 10 W/cm2. The
      accuracy of modeling was validated by comparison with direct measurements of the
      focal waveforms using a fiber-optic hydrophone. Simulation results and
      measurements show that shock fronts with amplitudes up to 100 MPa were present in
      focal waveforms at clinically relevant outputs, indicating the importance of
      strong nonlinear effects in ultrasound fields generated by HIFU arrays.

PMID- 26203344
TI  - Genome sequences of copper resistant and sensitive Enterococcus faecalis strains
      isolated from copper-fed pigs in Denmark.
AB  - Six strains of Enterococcus faecalis (S1, S12, S17, S18, S19 and S32) were
      isolated from copper fed pigs in Denmark. These Gram-positive bacteria within the
      genus Enterococcus are able to survive a variety of physical and chemical
      challenges by the acquisition of diverse genetic elements. The genome of strains
      S1, S12, S17, S18, S19 and S32 contained 2,615, 2,769, 2,625, 2,804, 2,853 and
      2,935 protein-coding genes, with 41, 42, 27, 42, 32 and 44 genes encoding
      antibiotic and metal resistance, respectively. Differences between Cu resistant
      and sensitive E. faecalis strains, and possible co-transfer of Cu and antibiotic
      resistance determinants were detected through comparative genome analysis. 

PMID- 26203346
TI  - Improved Detection of Kidney Stones Using an Optimized Doppler Imaging Sequence.
AB  - Kidney stones have been shown to exhibit a "twinkling artifact" (TA) under Color
      Doppler ultrasound. Although this technique has better specificity than
      conventional Bmode imaging, it has lower sensitivity. To improve the overall
      performance of using TA as a diagnostic tool, Doppler output parameters were
      optimized in-vitro. The collected data supports a previous hypothesis that TA is
      caused by random oscillations of micron sized bubbles trapped in the cracks and
      crevices of kidney stones. A set of optimized parameters were implemented such
      that that the MI & TI remained within the FDA approved limits. Several clinical
      kidney scans were performed with the optimized settings and were able to detect
      stones with improved SNR relative to the default settings.

PMID- 26203347
TI  - Ultrasonic propulsion of kidney stones: preliminary results of human feasibility
      study.
AB  - One in 11 Americans has experienced kidney stones, with a 50% average recurrence
      rate within 5-10 years. Ultrasonic propulsion (UP) offers a potential method to
      expel small stones or residual fragments before they become a recurrent problem.
      Reported here are preliminary findings from the first investigational use of UP
      in humans. The device uses a Verasonics ultrasound engine and Philips HDI C5-2
      probe to generate real-time B-mode imaging and targeted "push" pulses on demand.
      There are three arms of the study: de novo stones, post-lithotripsy fragments,
      and the preoperative setting. A pain questionnaire is completed prior to and
      following the study. Movement is classified based on extent. Patients are
      followed for 90 days. Ten subjects have been treated to date: three de novo, five
      post-lithotripsy, and two preoperative. None of the subjects reported pain
      associated with the treatment or a treatment related adverse event, beyond the
      normal discomfort of passing a stone. At least one stone was moved in all
      subjects. Three of five post-lithotripsy subjects passed a single or multiple
      stones within 1-2 weeks following treatment; one subject passed two (1-2 mm)
      fragments before leaving clinic. In the pre-operative studies we successfully
      moved 7 - 8 mm stones. In four subjects, UP revealed multiple stone fragments
      where the clinical image and initial ultrasound examination indicated a single
      large stone.

PMID- 26203348
TI  - Shockwave lithotripsy with renoprotective pause is associated with renovascular
      vasoconstriction in humans.
AB  - Animal studies have shown that shock wave lithotripsy (SWL) delivered with an
      initial course of low-energy shocks followed by a pause reduces renal injury. The
      pause correlates with increased arterial resistive index (RI) during SWL as
      measured by ultrasound. This suggests that renal vasoconstriction is associated
      with protecting the kidney from injury. This study explored whether a similar
      increase in RI is observed in humans. Patients were prospectively recruited from
      two hospitals. All received an initial dose of 250 lowest energy shocks followed
      by a two-minute pause. Shock power was then ramped up at the discretion of the
      physician; shock rate was maintained at 1 Hz. Spectral Doppler velocity
      measurements were taken from an interlobar artery at baseline after induction,
      during the pause at 250 shocks, after 750 shocks, after 1500 shocks, and at the
      end of the procedure. RI was calculated from the peak systolic and end diastolic
      velocities and a linear mixed-effects model was used to compare RIs. The
      statistical model accounted for age, gender, laterality, and body mass index
      (BMI). Measurements were taken from 15 patients. Average RI +/- standard
      deviation pretreatment, after 250 shocks, after 750 shocks, after 1500 shocks,
      and post treatment was 0.68 +/- 0.06, 0.71 +/- 0.07, 0.73 +/- 0.06, 0.75 +/- 0.07
      and 0.75 +/- 0.06, respectively. RI was found to be significantly higher after
      250 shocks compared to pretreatment (p = 0.04). RI did not correlate with age,
      gender, BMI, or treatment side. This is suggestive that allowing a pause for
      renal vascular vasoconstriction to develop may be beneficial, and can be
      monitored for during SWL, providing real-time feedback as to when the kidney is
      protected.

PMID- 26203349
TI  - Medium frequency propagation characteristics of different transmission lines in
      an underground coal mine.
AB  - A medium frequency (MF) communication system operating in an underground coal
      mine couples its signals to a long conductor, which acts as an MF transmission
      line (TL) in a tunnel to permit communications among transceivers along the line.
      The TL is generally the longest signal path for the system, and its propagation
      characteristics will have a major impact on the performance of the MF
      communication system. In this study, the propagation characteristics of three
      types of MF TLs in two layouts-on the roof and on the floor of a coal mine tunnel
      were obtained in an effort to understand the propagation characteristics of
      different TLs in different locations. The study confirmed a low MF signal loss on
      all of these TLs. The study also found that the TLs in different layouts had
      substantially different propagation characteristics. The propagation
      characteristics of these different TLs in different layouts are presented in the
      paper.

PMID- 26203350
TI  - Regions of ryanodine receptors that influence activation by the dihydropyridine
      receptor beta1a subunit.
AB  - BACKGROUND: Although excitation-contraction (EC) coupling in skeletal muscle
      relies on physical activation of the skeletal ryanodine receptor (RyR1) Ca(2+)
      release channel by dihydropyridine receptors (DHPRs), the activation pathway
      between the DHPR and RyR1 remains unknown. However, the pathway includes the DHPR
      beta1a subunit which is integral to EC coupling and activates RyR1. In this
      manuscript, we explore the isoform specificity of beta1a activation of RyRs and
      the beta1a binding site on RyR1. METHODS: We used lipid bilayers to measure
      single channel currents and whole cell patch clamp to measure L-type Ca(2+)
      currents and Ca(2+) transients in myotubes. RESULTS: We demonstrate that both
      skeletal RyR1 and cardiac RyR2 channels in phospholipid bilayers are activated by
      10-100 nM of the beta1a subunit. Activation of RyR2 by 10 nM beta1a was less than
      that of RyR1, suggesting a reduced affinity of RyR2 for beta1a. A reduction in
      activation was also observed when 10 nM beta1a was added to the alternatively
      spliced (ASI(-)) isoform of RyR1, which lacks ASI residues (A3481-Q3485). It is
      notable that the equivalent region of RyR2 also lacks four of five ASI residues,
      suggesting that the absence of these residues may contribute to the reduced 10 nM
      beta1a activation observed for both RyR2 and ASI(-)RyR1 compared to ASI(+)RyR1.
      We also investigated the influence of a polybasic motif (PBM) of RyR1
      (K3495KKRRDGR3502) that is located immediately downstream from the ASI residues
      and has been implicated in EC coupling. We confirmed that neutralizing the basic
      residues in the PBM (RyR1 K-Q) results in an ~50 % reduction in Ca(2+) transient
      amplitude following expression in RyR1-null (dyspedic) myotubes and that the PBM
      is also required for beta1a subunit activation of RyR1 channels in lipid
      bilayers. These results suggest that the removal of beta1a subunit interaction
      with the PBM in RyR1 could contribute directly to ~50 % of the Ca(2+) release
      generated during skeletal EC coupling. CONCLUSIONS: We conclude that the beta1a
      subunit likely binds to a region that is largely conserved in RyR1 and RyR2 and
      that this region is influenced by the presence of the ASI residues and the PBM in
      RyR1.

PMID- 26203351
TI  - Tip110 binding to U6 small nuclear RNA and its participation in pre-mRNA
      splicing.
AB  - BACKGROUND: RNA-protein interactions play important roles in gene expression
      control. These interactions are mediated by several recurring RNA-binding motifs
      including a well-known and characterized ribonucleoprotein motif or so-called RNA
      recognition motif (RRM). RESULTS: In the current study, we set out to identify
      the RNA ligand(s) of a RRM-containing protein Tip110, also known as p110(nrb),
      SART3, or p110, using a RNA-based yeast three-hybrid cloning strategy. Six
      putative RNA targets were isolated and found to contain a consensus sequence that
      was identical to nucleotides 34-46 of U6 small nuclear RNA. Tip110 binding to U6
      was confirmed to be specific and RRM-dependent in an electrophoretic mobility
      shift assay. Both in vitro pre-mRNA splicing assay and in vivo splicing-dependent
      reporter gene assay showed that the pre-mRNA splicing was correlated with Tip110
      expression. Moreover, Tip110 was found in the spliceosomes containing pre-spliced
      pre-mRNA and spliced mRNA products. Nonetheless, the RRM-deleted mutant
      (DeltaRRM) that did not bind to U6 showed promotion in vitro pre-mRNA splicing,
      whereas the nuclear localization signal (NLS)-deleted mutant DeltaNLS that bound
      to U6 promoted the pre-mRNA splicing both in vitro and in vivo. Lastly, RNA-Seq
      analysis confirmed that Tip110 regulated a number of gene pre-mRNA splicing
      including several splicing factors. CONCLUSIONS: Taken together, these results
      demonstrate that Tip110 is directly involved in constitutive eukaryotic pre-mRNA
      splicing, likely through its binding to U6 and regulation of other splicing
      factors, and provide further evidence to support the global roles of Tip110 in
      regulation of host gene expression.

PMID- 26203352
TI  - Nematode control in suckler beef cattle over their first two grazing seasons
      using a targeted selective treatment approach.
AB  - BACKGROUND: With concerns over the development of anthelmintic resistance in
      cattle nematode populations, we must re-examine our approach to nematode control
      in cattle. Targeted selective treatments (TST), whereby individual animals are
      treated instead of entire groups, are being investigated as an alternative. The
      study objective was to determine if anthelmintic usage could be reduced using a
      TST-based approach to nematode control in spring-born suckler beef cattle over
      their first and second grazing seasons (SGS) without affecting performance. In
      the first grazing season (FGS), 99 calves with an initial mean (s.d.) calf age
      and live weight on day 0 (June 28(th) 2012) of 107 (23.1) days and 160 (32.5) kg,
      respectively, were used. The study commenced on day 0 when calves were randomised
      and allocated to one of two treatments; 1), standard treatment (control) and 2),
      TST. Control calves were treated subcutaneously with ivermectin on days 0, 41 and
      82 in the FGS. All calves were treated with ivermectin on day 124 and housed on
      day 133. In the SGS, only heifer calves from the FGS were used and control
      heifers were treated with ivermectin on day 393. Animals were weighed, blood and
      faecal sampled every three weeks. The TST animals were treated with ivermectin if
      thresholds based on a combination of plasma pepsinogen concentrations, faecal egg
      count and/or the presence of Dictyocaulus viviparus larvae in faeces (FGS only)
      were reached. RESULTS: No TST calves reached the treatment threshold criteria in
      the FGS. The FGS average daily live weight gain (ADG +/- s.e.m.) for control and
      TST group calves was 0.89 +/- 0.02 kg and 0.94 +/- 0.02 kg day(-1), respectively
      (P = 0.17). In the SGS, all heifers were treated with ivermectin on day 431 due
      to clinical signs of respiratory disease. The ADG for control and TST heifers
      from turnout on day 321 to day 431 was 0.90 +/- 0.04 and 0.80 +/- 0.04 kg day(
      1), respectively (P = 0.03). CONCLUSIONS: Spring-born FGS suckler beef calves
      require minimal anthelmintic treatment to maintain performance. In contrast,
      clinical parasitic disease may develop in the SGS unless appropriate anthelmintic
      treatment is provided.

PMID- 26203353
TI  - Stroke volume variation to guide fluid therapy: is it suitable for high-risk
      surgical patients? A terminated randomized controlled trial.
AB  - BACKGROUND: Perioperative goal-directed fluid therapy (GDFT) may improve outcome
      after high-risk surgery. Minimal invasive measurement of stroke volume variation
      (SVV) has been recommended to guide fluid therapy. We intended to study how
      perioperative GDFT with arterial-based continuous SVV monitoring influences
      postoperative complications in a high-risk surgical population. METHODS: From
      February 1st 2012, all ASA 3 and 4 patients undergoing abdominal surgery in two
      university hospitals were assessed for randomization into a control group or GDFT
      group. An arterial-line cardiac output monitor was used to measure SVV, and fluid
      was given after an algorithm in the intervention group. Restrictions of the
      method excluded patients undergoing laparoscopic surgery, patients with atrial
      fibrillation and patients with severe mitral/aortal stenosis. To detect a
      decrease in number of complication from 40 % in the control group to 20 % in the
      GDFT group, n = 164 patients were needed (power 80 %, alpha 0.05, two-sided
      test). To include the needed amount of patients, the study was estimated to last
      for 2 years. RESULTS: After 1 year, 30 patients were included and the study was
      halted due to slow inclusion rate. Of 732 high-risk patients scheduled for
      abdominal surgery, 391 were screened for randomization. Of those, n = 249 (64 %)
      were excluded because a laparoscopic technique was preferred and n = 95 (24 %)
      due to atrial fibrillation. CONCLUSIONS: Our study was stopped due to a slow
      inclusion rate. Methodological restrictions of the arterial-line cardiac output
      monitor excluded the majority of patients. This leaves the question if this
      method is appropriate to guide fluid therapy in high-risk surgical patients.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT01473446.

PMID- 26203354
TI  - The whole truth and nothing but the truth: the need for full reporting of
      randomised trials.
AB  - The use of cardiac output monitoring to guide fluid and inotropic therapy in
      surgical patients has remained a controversial topic for more than 40 years. The
      reasons for this are numerous and complex, but key amongst them is the interplay
      between poor research methodology and the likely selective reporting of
      randomised trials. In this issue of Perioperative Medicine, we find a very
      unusual report, one which describes a randomised trial stopped for futility after
      the recruitment of only a small proportion of the target patient sample (Jammer
      et al. Periop Med). The authors offer no statistical analysis of their findings
      but simply an explanation of what went wrong. On the face of it, this exercise
      would seem to offer little of value to the general reader. How can publication of
      the findings of an unsuccessful trial contribute to the evidence base on this
      topic? To understand this, we must delve a little deeper into the evidence and
      see how these trials were designed. 

PMID- 26203355
TI  - Contraindications to kidney transplantation: uneven grounds?
AB  - BACKGROUND: Determining eligibility for a kidney transplant is an important
      decision. Practice guidelines define contraindications to transplantation;
      however many are not evidence based. Canadian guidelines recommend that patients
      unlikely to survive the wait period not be evaluated. The purpose of this study
      was to evaluate what proportion of patients with a contraindication would survive
      the wait time. METHODS: Consecutive incident dialysis patients (January 2006 to
      December 2012) with a contraindication, defined using Canadian guidelines, were
      studied. Mortality rates were determined for each individual contraindication.
      Theoretical survival to the median wait time to transplantation was calculated.
      RESULTS: Of 746 incident patients, 435 (58 %) were deemed to have a
      contraindication at dialysis start. Nearly 80 % had a contraindication with a
      high mortality rate (dementia, multisystem disease, etc.). Patients with high
      mortality rates were less likely to survive the wait list than be transplanted.
      Patients with non-adherence, obesity, and potentially reversible disease had
      relatively low mortality rates, were more likely to survive, and possibly be
      transplanted at a time with the prospect of a better outcome. CONCLUSIONS: This
      study gives some credence that many patients with a contraindication are not
      likely to benefit. A better framework of defining contraindications is needed to
      allow better decision-making.

PMID- 26203356
TI  - A case of B-cell acute lymphoblastic leukemia in a child with Down syndrome
      bearing a t(2;12)(p12;p13) involving ETV6 and biallelic IGH@ rearrangements.
AB  - BACKGROUND: Rearrangements involving ETV6 (12p13) are among the most common
      structural abnormalities in pediatric B-cell acute lymphoblastic leukemia (B-ALL)
      and involve numerous partner genes. Additionally, the t(8;14)(q11.2;q32), which
      can result in the placement of CEBPD (8q11.2) near the regulatory regions of IGH@
      (14q32) and consequent overexpression of CEPBD, occurs at a higher frequency in
      individuals with Down syndrome-associated ALL (DS-ALL) compared to both the
      general and pediatric population. The coexistence of cytogenetically detectable
      ETV6 abnormalities and t(8;14)(q11.2;q32) is a rare occurrence in B-ALL and has
      only been reported in a single case in the literature. FINDINGS: Herein, we
      present a case of B-ALL in a 9-year old male with Down syndrome in which
      conventional cytogenetic analysis revealed two reciprocal translocations: a
      t(8;14)(q11.2;q32) and a t(2;12)(p12;p13). Interphase and metaphase fluorescence
      in situ hybridization (FISH) analysis using break apart probes confirmed the
      involvement of IGH@ and ETV6 in these translocations, respectively. Additionally,
      interphase FISH revealed a clonal subpopulation bearing biallelic IGH@
      rearrangements not observed by conventional cytogenetic analysis. CONCLUSIONS: To
      the best of our knowledge, this is the first reported case of B-ALL bearing an
      ETV6 translocation with a partner gene on the short arm of chromosome 2 confirmed
      by FISH. Additionally, it is the second reported case of t(8;14)(q11.2;q32)-ALL
      bearing a concomitant, cytogenetically detectable abnormality involving ETV6.
      This case provides insight into a novel translocation involving ETV6 as well as
      potentially unique and understudied mechanisms of clonal evolution in pediatric B
      ALL.

PMID- 26203357
TI  - Prognostic models for alcoholic hepatitis.
AB  - Alcoholic hepatitis (AH) is caused by acute inflammation of the liver in patients
      that consume excessive amounts of alcohol, usually in a background of cirrhosis.
      AH can range from mild to severe, life threatening disease with a high rate of
      short and long-term mortality. Prognostic models have been used to estimate
      mortality in order to identify those that may benefit from corticosteroids or
      pentoxifylline. This review focuses on the different prognostic models proposed.
      While limitations of the prognostic models exist, combining models may be
      beneficial in order to identify responders to therapy versus non-responders. 

PMID- 26203358
TI  - Explaining the slow transition of child-appropriate dosage formulations from the
      global to national level in the context of Uganda: a qualitative study.
AB  - BACKGROUND: In 2007, the Sixtieth World Health Assembly (WHA) passed a resolution
      entitled "Better medicines for children" and subsequently the World Health
      Organization (WHO) recommended the inclusion of child-appropriate dosage
      formulations in the essential medicines lists of member countries. However, child
      appropriate dosage formulations are not highlighted in the Essential Medicines
      and Health Supplies List of Uganda (EMHSLU) 2012 and they are still limited in
      availability in public health facilities. Several stakeholders influenced the
      status of child-appropriate dosage formulations in the EMHSLU 2012. OBJECTIVE: To
      explore stakeholders' views about the relevance of the globally recommended child
      appropriate dosage formulations in the context of Uganda. METHODS: The findings
      derive from thirty three in-depth interviews with stakeholder representatives and
      the results of a follow up validation meeting where preliminary findings were
      shared with stakeholders. Policy analysis and policy transfer theories were used
      to guide a deductive analysis for manifest and latent content. RESULTS: According
      to stakeholders, the transition to the globally recommended child-appropriate
      dosage formulations has been slow in Uganda due to a number of factors. These
      factors include resource constraints at the global and national levels, lack of
      Ministry of Health (MOH) formal commitment to the adoption of the child
      appropriate dosage formulations policy and a lack of consensus between those who
      advocated for the availability of liquid oral dosage formulations for easy
      administration and effectiveness and those who were more convinced by economic
      arguments and preferred the procurement of solid oral dosage formulations
      intended for adults. CONCLUSIONS: The global policy for child-appropriate dosage
      formulations still remains to be implemented in Uganda and other low income
      countries. This has been due to lack of resources that hindered formal transfer
      of the policy from the global to the local level. To achieve this transfer there
      is a need for resource mobilisation at both the international and local levels,
      together with the revitalisation of UMTAC to enable it to take on a leadership
      role of the coalitions supporting child-appropriate dosage formulations.

PMID- 26203359
TI  - Carcinoid tumours of the lung and the 'PEPPS' approach: evaluation of
      preoperative bronchoscopic tumour debulking as preparation for subsequent
      parenchyma-sparing surgery.
AB  - BACKGROUND: Preoperative bronchoscopic tumour ablation has been suggested as a
      beneficial treatment for bronchopulmonary carcinoid tumours, although data
      regarding its effects and long-term outcome are lacking. METHODS: In our case
      matched cohort study with 208 patients with bronchopulmonary carcinoid tumours we
      investigated the role of preoperative bronchoscopic interventions before
      subsequent surgery and analysed the safety of this Procedure of Endobronchial
      Preparation for Parenchyma-sparing Surgery (PEPPS) based on metastasis and
      recurrence rates as well as survival data from 1991 to 2010. The subsequent
      surgery was classified into parenchyma-sparing procedures and classical
      lobectomies, bilobectomies and pneumonectomies. Data were obtained from the
      tumour registry and medical reports. Outcomes were the frequency of parenchyma
      sparing surgery after bronchoscopic treatment as well as rates of metastasis,
      recurrence and survival. RESULTS: 132 of 208 carcinoids were located centrally.
      Among them, 77 patients could be recanalised preoperatively. After bronchoscopic
      preparation, the rate of subsequent parenchyma-sparing surgery methods was higher
      (p=0.021). The effect was measured by the number of segments removed. The 10-year
      survival rate was 89% (typical carcinoids) and 68% (atypical carcinoids),
      respectively. After applying PEPPS, long-term survival was slightly higher
      (p=0.23). Metastasis and recurrence rates showed no relevant differences between
      the bronchoscopically treated or non-treated groups, or between the two types of
      surgery classes or between the PEPPS and non-PEPPS groups. CONCLUSIONS: After
      preoperative bronchoscopic treatment, parenchyma-sparing surgery techniques can
      be applied more frequently. Furthermore, we detected no negative effects after
      PEPPS based on metastasis, recurrence and survival rates.

PMID- 26203360
TI  - Effect of a 1-week, eucaloric, moderately high-fat diet on peripheral insulin
      sensitivity in healthy premenopausal women.
AB  - OBJECTIVES: To determine whether a weight-maintaining, moderate (50%) high-fat
      diet is deleterious to insulin sensitivity in healthy premenopausal women.
      DESIGN/SETTING/PARTICIPANTS: 23 African-American and non-Hispanic white, healthy,
      overweight, and obese premenopausal women recruited in New York City, USA, fed
      either a eucaloric, 1-week long high-fat (50% of total Kcal from fat) diet or a
      eucaloric, 1-week long low-fat (30% of total Kcal from fat) diet, assigned in a
      randomized crossover design. MAIN OUTCOME MEASURES: Peripheral insulin
      sensitivity and metabolic flexibility during a euglycemic hyperinsulinemic (80
      mU/m(2)/min) clamp measured during the follicular phase of the menstrual cycle,
      at the end of each diet period. RESULTS: Peripheral insulin sensitivity (mg
      kg/fat-free mass/min (uU/mL)*10(-1)) was not decreased after the high-fat diet vs
      the low-fat diet (0.09+/-0.01 vs 0.08+/-0.01, p=0.09, respectively) in the
      combined group of African-American and white women, with no significant diet by
      race interaction (p=0.6). Metabolic flexibility (change in substrate utilization,
      DeltaNPRQ, in response to insulin during the clamp) was similarly unaltered by
      the diet (0.12+/-0.01 vs 0.11, p=0.48, for the high-fat diet vs the low-fat diet,
      respectively) in the combined group of women, with no significant diet by race
      interaction (p=0.9). African-American women had a lower insulin clearance
      compared with the white women, regardless of the diet (p<0.05). CONCLUSIONS: We
      conclude that a short term (1 week), moderate (50%), eucaloric high-fat diet does
      not lower peripheral insulin sensitivity in healthy, overweight and obese
      premenopausal women.

PMID- 26203361
TI  - Multimodal nonlinear endo-microscopy probe design for high resolution, label-free
      intraoperative imaging.
AB  - We present a portable, multimodal, nonlinear endo-microscopy probe designed for
      intraoperative oncological imaging. Application of a four-wave mixing noise
      suppression scheme using dual wavelength wave plates (DWW) and a polarization
      maintaining fiber improves tissue signal collection efficiency, allowing for
      miniaturization. The probe, with a small 14 mm transversal diameter, includes a
      customized miniaturized two-axis MEMS (micro-electromechanical system) raster
      scanning mirror and micro-optics with an illumination laser delivered by a
      polarization-maintaining fiber. The probe can potentially be integrated into the
      arms of a surgical robot, such as da Vinci robotic surgery system, due to its
      minimal cross sectional area. It has the ability to incorporate multiple imaging
      modalities including CARS (coherent anti-Stokes Raman scattering), SHG (second
      harmonic generation), and TPEF (two-photon excited fluorescence) in order to
      allow the surgeon to locate tumor cells within the context of normal stromal
      tissue. The resolution of the endo-microscope is experimentally determined to be
      0.78 um, a high level of accuracy for such a compact probe setup. The expected
      resolution of the as-built multimodal, nonlinear, endo-microscopy probe is 1 um
      based on the calculation tolerance allocation using Monte-Carlo simulation. The
      reported probe is intended for use in laparoscopic or radical prostatectomy,
      including detection of tumor margins and avoidance of nerve impairment during
      surgery. 

PMID- 26203362
TI  - Rapid three-dimensional quantification of voxel-wise collagen fiber orientation.
AB  - Defining fiber orientation at each voxel within a 3D biomedical image stack is
      potentially useful for a variety of applications, including cancer, wound healing
      and tissue regeneration. Current methods are typically computationally intensive
      or inaccurate. Herein, we present a 3D weighted orientation vector summation
      algorithm, which is a generalization of a previously reported 2D vector summation
      technique aimed at quantifying collagen fiber orientations simultaneously at each
      voxel of an image stack. As a result, voxel-wise fiber orientation information
      with 4 degrees  to 5 degrees  accuracy can be determined, and the computational
      time required to analyze a typical stack with the size of 512x512x100 voxels is
      less than 5 min. Thus, this technique enables the practical extraction of voxel
      specific orientation data for characterizing structural anisotropy in 3D
      specimens. As examples, we use this approach to characterize the fiber
      organization in an excised mouse mammary gland and a 3D breast tissue model. 

PMID- 26203363
TI  - Confocal foveated endomicroscope for the detection of esophageal carcinoma.
AB  - By mimicking the variable resolution of the human eye, a newly designed foveated
      endomicroscopic objective shows the potential to improve current endoscopic based
      techniques of identifying abnormal tissue in the esophagus and colon. The
      prototype miniature foveated objective is imaged with a confocal microscope to
      provide large field of view images combined with a high resolution central region
      to rapidly observe morphological structures associated with cancer development in
      a mouse model. 

PMID- 26203364
TI  - Fiber based optical tweezers for simultaneous in situ force exertion and
      measurements in a 3D polyacrylamide gel compartment.
AB  - Optical tweezers play an important role in biological applications. However, it
      is difficult for traditional optical tweezers based on objective lenses to work
      in a three-dimensional (3D) solid far away from the substrate. In this work, we
      develop a fiber based optical trapping system, namely inclined dual fiber optical
      tweezers, that can simultaneously apply and measure forces both in water and in a
      3D polyacrylamide gel matrix. In addition, we demonstrate in situ, non-invasive
      characterization of local mechanical properties of polyacrylamide gel by
      measurements on an embedded bead. The fiber optical tweezers measurements agree
      well with those of atomic force microscopy (AFM). The inclined dual fiber optical
      tweezers provide a promising and versatile tool for cell mechanics study in 3D
      environments. 

PMID- 26203365
TI  - Dynamic functional connectivity revealed by resting-state functional near
      infrared spectroscopy.
AB  - The brain is a complex network with time-varying functional connectivity (FC) and
      network organization. However, it remains largely unknown whether resting-state
      fNIRS measurements can be used to characterize dynamic characteristics of
      intrinsic brain organization. In this study, for the first time, we used the
      whole-cortical fNIRS time series and a sliding-window correlation approach to
      demonstrate that fNIRS measurement can be ultimately used to quantify the dynamic
      characteristics of resting-state brain connectivity. Our results reveal that the
      fNIRS-derived FC is time-varying, and the variability strength (Q) is correlated
      negatively with the time-averaged, static FC. Furthermore, the Q values also show
      significant differences in connectivity between different spatial locations
      (e.g., intrahemispheric and homotopic connections). The findings are reproducible
      across both sliding-window lengths and different brain scanning sessions,
      suggesting that the dynamic characteristics in fNIRS-derived cerebral functional
      correlation results from true cerebral fluctuation. 

PMID- 26203366
TI  - Multiscattering-enhanced optical biosensor: multiplexed, non-invasive and
      continuous measurements of cellular processes.
AB  - The continuous measurement of uptake or release of biomarkers provides invaluable
      information for understanding and monitoring the metabolism of cells. In this
      work, a multiscattering-enhanced optical biosensor for the multiplexed, non
      invasive, and continuous detection of hydrogen peroxide (H2O2), lactate and
      glucose is presented. The sensing scheme is based on optical monitoring of the
      oxidation state of the metalloprotein cytochrome c (cyt c). The analyte of
      interest is enzymatically converted into H2O2 leading to an oxidation of the cyt
      c. Contact microspotting is used to prepare nanoliter-sized sensing spots
      containing either pure cyt c, a mixture of cyt c with glucose oxidase (GOx) to
      detect glucose, or a mixture of cyt c with lactate oxidase (LOx) to detect
      lactate. The sensing spots are embedded in a multiscattering porous medium that
      enhances the optical signal. We achieve limits of detection down to 240 nM and
      110 nM for lactate and glucose, respectively. A microfluidic embodiment enables
      multiplexed and crosstalk-free experiments on living organisms. As an example, we
      study the uptake of exogenously supplied glucose by the green algae Chlamydomonas
      reinhardtii and simultaneously monitor the stress-related generation of H2O2.
      This multifunctional detection scheme provides a powerful tool to study
      biochemical processes at cellular level. 

PMID- 26203367
TI  - Characterization of structural-prior guided optical tomography using realistic
      breast models derived from dual-energy x-ray mammography.
AB  - Multi-spectral near-infrared diffuse optical tomography (DOT) is capable of
      providing functional tissue assessment that can complement structural
      mammographic images for more comprehensive breast cancer diagnosis. To take full
      advantage of the readily available sub-millimeter resolution structural
      information in a multi-modal imaging setting, an efficient x-ray/optical joint
      image reconstruction model has been proposed previously to utilize anatomical
      information from a mammogram as a structural prior. In this work, we develop a
      complex digital breast phantom (available at http://openjd.sf.net/digibreast)
      based on direct measurements of fibroglandular tissue volume fractions using dual
      energy mammographic imaging of a human breast. We also extend our prior-guided
      reconstruction algorithm to facilitate the recovery of breast tumors, and perform
      a series of simulation-based studies to systematically evaluate the impact of
      lesion sizes and contrasts, tissue background, mesh resolution, inaccurate
      priors, and regularization parameters, on the recovery of breast tumors using
      multi-modal DOT/x-ray measurements. Our studies reveal that the optical property
      estimation error can be reduced by half by utilizing structural priors; the
      minimum detectable tumor size can also be reduced by half when prior knowledge
      regarding the tumor location is provided. Moreover, our algorithm is shown to be
      robust to false priors on tumor location. 

PMID- 26203368
TI  - Characterization of a Raman spectroscopy probe system for intraoperative brain
      tissue classification.
AB  - A detailed characterization study is presented of a Raman spectroscopy system
      designed to maximize the volume of resected cancer tissue in glioma surgery based
      on in vivo molecular tissue characterization. It consists of a hand-held probe
      system measuring spectrally resolved inelastically scattered light interacting
      with tissue, designed and optimized for in vivo measurements. Factors such as
      linearity of the signal with integration time and laser power, and their impact
      on signal to noise ratio, are studied leading to optimal data acquisition
      parameters. The impact of ambient light sources in the operating room is assessed
      and recommendations made for optimal operating conditions. In vivo Raman spectra
      of normal brain, cancer and necrotic tissue were measured in 10 patients,
      demonstrating that real-time inelastic scattering measurements can distinguish
      necrosis from vital tissue (including tumor and normal brain tissue) with an
      accuracy of 87%, a sensitivity of 84% and a specificity of 89%. 

PMID- 26203369
TI  - Optical coherence tomography-based parameterization and quantification of
      articular cartilage surface integrity.
AB  - Loss of articular cartilage surface integrity is considered the earliest sign of
      osteoarthritis; however, its reliable detection has not been established by
      clinical routine diagnostics. This study comprehensively assesses a set of 11
      algorithm-based 2-D Optical Coherence Tomography roughness parameters and
      investigates their clinical impact. Histology and manual irregularity
      quantification of 105 human cartilage samples with variable degeneration served
      as reference. The majority of parameters revealed a close-to-linear correlation
      with the entire spectrum of degeneration. Surface integrity should therefore be
      assessed by a combination of parameters to improve current diagnostic accuracy in
      the determination of cartilage degeneration. 

PMID- 26203370
TI  - Active eye-tracking for an adaptive optics scanning laser ophthalmoscope.
AB  - We demonstrate a system that combines a tracking scanning laser ophthalmoscope
      (TSLO) and an adaptive optics scanning laser ophthalmoscope (AOSLO) system
      resulting in both optical (hardware) and digital (software) eye-tracking
      capabilities. The hybrid system employs the TSLO for active eye-tracking at a
      rate up to 960 Hz for real-time stabilization of the AOSLO system. AOSLO videos
      with active eye-tracking signals showed, at most, an amplitude of motion of 0.20
      arcminutes for horizontal motion and 0.14 arcminutes for vertical motion.
      Subsequent real-time digital stabilization limited residual motion to an average
      of only 0.06 arcminutes (a 95% reduction). By correcting for high amplitude, low
      frequency drifts of the eye, the active TSLO eye-tracking system enabled the
      AOSLO system to capture high-resolution retinal images over a larger range of
      motion than previously possible with just the AOSLO imaging system alone. 

PMID- 26203371
TI  - Multigrid-based reconstruction algorithm for quantitative photoacoustic
      tomography.
AB  - This paper proposes a multigrid inversion framework for quantitative
      photoacoustic tomography reconstruction. The forward model of optical fluence
      distribution and the inverse problem are solved at multiple resolutions. A fixed
      point iteration scheme is formulated for each resolution and used as a cost
      function. The simulated and experimental results for quantitative photoacoustic
      tomography reconstruction show that the proposed multigrid inversion can
      dramatically reduce the required number of iterations for the optimization
      process without loss of reliability in the results. 

PMID- 26203372
TI  - Image quality metrics for optical coherence angiography.
AB  - We characterized image quality in optical coherence angiography (OCA) en face
      planes of mouse cortical capillary network in terms of signal-to-noise ratio
      (SNR) and Weber contrast (Wc) through a novel mask-based segmentation method. The
      method was used to compare two adjacent B-scan processing algorithms, (1) average
      absolute difference (AAD) and (2) standard deviation (SD), while varying the
      number of lateral cross-sections acquired (also known as the gate length, N). AAD
      and SD are identical at N = 2 and exhibited similar image quality for N<10.
      However, AAD is relatively less susceptible to bulk tissue motion artifact than
      SD. SNR and Wc were 15% and 35% higher for AAD from N = 25 to 100. In addition
      data sets were acquired with two objective lenses with different magnifications
      to quantify the effect of lateral resolution on fine capillary detection. The
      lower power objective yielded a significant mean broadening of 17% in Full Width
      Half Maximum (FWHM) diameter. These results may guide study and device designs
      for OCA capillary and blood flow quantification. 

PMID- 26203373
TI  - Wavelength shifting of intra-cavity photons: Adiabatic wavelength tuning in
      rapidly wavelength-swept lasers.
AB  - We analyze the physics behind the newest generation of rapidly wavelength tunable
      sources for optical coherence tomography (OCT), retaining a single longitudinal
      cavity mode during operation without repeated build up of lasing. In this
      context, we theoretically investigate the currently existing concepts of rapidly
      wavelength-swept lasers based on tuning of the cavity length or refractive index,
      leading to an altered optical path length inside the resonator. Specifically, we
      consider vertical-cavity surface-emitting lasers (VCSELs) with
      microelectromechanical system (MEMS) mirrors as well as Fourier domain mode
      locked (FDML) and Vernier-tuned distributed Bragg reflector (VT-DBR) lasers.
      Based on heuristic arguments and exact analytical solutions of Maxwell's
      equations for a fundamental laser resonator model, we show that adiabatic
      wavelength tuning is achieved, i.e., hopping between cavity modes associated with
      a repeated build up of lasing is avoided, and the photon number is conserved. As
      a consequence, no fundamental limit exists for the wavelength tuning speed, in
      principle enabling wide-range wavelength sweeps at arbitrary tuning speeds with
      narrow instantaneous linewidth. 

PMID- 26203374
TI  - Dynamic heart rate measurements from video sequences.
AB  - This paper shows how dynamic heart rate measurements that are typically obtained
      from sensors mounted near to the heart can also be obtained from video sequences.
      In this study, two experiments are carried out where a video camera captures the
      facial images of the seven subjects. The first experiment involves the
      measurement of subjects' increasing heart rates (79 to 150 beats per minute
      (BPM)) while cycling whereas the second involves falling heart beats (153 to 88
      BPM). In this study, independent component analysis (ICA) is combined with mutual
      information to ensure accuracy is not compromised in the use of short video
      duration. While both experiments are going on measures of heartbeat using the
      Polar heart rate monitor is also taken to compare with the findings of the
      proposed method. Overall experimental results show the proposed method can be
      used to measure dynamic heart rates where the root mean square error (RMSE) and
      the correlation coefficient are 1.88 BPM and 0.99 respectively. 

PMID- 26203375
TI  - Dual band dual focus optical coherence tomography for imaging the whole eye
      segment.
AB  - We developed an improved dual band dual focus spectral domain optical coherence
      tomography (SD-OCT) for in vivo 2D/3D imaging of the whole eye segment, including
      the whole anterior segment and retina. The system featured two OCT channels with
      two different bands centered at 840 nm and 1050 nm, which were designed to image
      the retina and the anterior segments of the eye, respectively. By combing the two
      probe light beams for co-axial scanning and separating them for focusing at
      different segments of the eye with a combination of three dichroic mirrors, we
      not only minimized the loss of the backscattered light from the sample but also
      improved the imaging depth, scan range and resolution. The full resolved complex
      (FRC) method was applied to double the imaging depth for the whole anterior
      segment imaging, with which an imaging depth of 36.71 mm in air was achieved. We
      demonstrated that this system was capable of measuring the dynamic changes of
      ocular dimensions, including the asphericity of the cornea and lens, during
      accommodation. 

PMID- 26203376
TI  - Near-infrared spectroscopy integrated catheter for characterization of myocardial
      tissues: preliminary demonstrations to radiofrequency ablation therapy for atrial
      fibrillation.
AB  - Effects of radiofrequency ablation (RFA) treatment of atrial fibrillation can be
      limited by the ability to characterize the tissue in contact. Parameters obtained
      by conventional catheters, such as impedance and temperature can be insufficient
      in providing physiological information pertaining to effective treatment. In this
      report, we present a near-infrared spectroscopy (NIRS)-integrated catheter
      capable of extracting tissue optical properties. Validation experiments were
      first performed in tissue phantoms with known optical properties. We then apply
      the technique for characterization of myocardial tissues in swine and human
      hearts, ex vivo. Additionally, we demonstrate the recovery of critical parameters
      relevant to RFA therapy including contact verification, and lesion transmurality.
      These findings support the application of NIRS for improved guidance in RFA
      therapeutic interventions. 

PMID- 26203377
TI  - In vivo visualization of skin inflammation by optical coherence tomography and
      two-photon microscopy.
AB  - Inflammation is a non-specific immune response to injury intended to protect
      biological tissue from harmful stimuli such as pathogens, irritants, and damaged
      cells. In vivo optical tissue imaging has been used to provide spatial and
      dynamic characteristics of inflammation within the tissue. In this paper, we
      report in vivo visualization of inflammation in the skin at both cellular and
      physiological levels by using a combination of label-free two-photon microscopy
      (TPM) and optical coherence tomography (OCT). Skin inflammation was induced by
      topically applying lipopolysaccharide (LPS) on the mouse ear. Temporal OCT
      imaging visualized tissue swelling, vasodilation, and increased capillary density
      30 min and 1 hour after application. TPM imaging showed immune cell migration
      within the inflamed skin. Combined OCT and TPM was applied to obtain
      complementary information from each modality in the same region of interest. The
      information provided by each modality were consistent with previous reports about
      the characteristics of inflammation. Therefore, the combination of OCT and TPM
      holds potential for studying inflammation of the skin. 

PMID- 26203378
TI  - Photoacoustic imaging of fluorophores using pump-probe excitation.
AB  - A pump-probe technique for the detection of fluorophores in tomographic PA images
      is introduced. It is based on inducing stimulated emission in fluorescent
      molecules, which in turn modulates the amount of thermalized energy, and hence
      the PA signal amplitude. A theoretical model of the PA signal generation in
      fluorophores is presented and experimentally validated on cuvette measurements
      made in solutions of Rhodamine 6G, a fluorophore of known optical and molecular
      properties. The application of this technique to deep tissue tomographic PA
      imaging is demonstrated by determining the spatial distribution of a near
      infrared fluorophore in a tissue phantom. 

PMID- 26203379
TI  - Measurement of the refractive index of hemoglobin solutions for a continuous
      spectral region.
AB  - Determination of the refractive index of hemoglobin solutions over a wide
      wavelength range remains challenging. A famous detour approach is the Kramers
      Kronig (KK) analysis which can resolve the real part of complex refractive index
      from the imaginary part. However, KK analysis is limited by the contradiction
      between the requirement of semi-infinite frequency range and limited measured
      range. In this paper, based on the Multi-curve fitting method (MFM), continuous
      refractive index dispersion (CRID) of oxygenated and deoxygenated hemoglobin
      solutions are measured using a homemade symmetrical arm-linked apparatus in the
      continuous wavelength range with spectral resolution of about 0.259nm. A novel
      method to obtain the CRID is proposed. 

PMID- 26203380
TI  - Correlation between polarization sensitive optical coherence tomography and
      second harmonic generation microscopy in skin.
AB  - Both polarization sensitive optical coherence tomography (PS-OCT) and second
      harmonic generation (SHG) microscopy are 3D optical imaging methods providing
      information related to collagen in the skin. PS-OCT provides birefringence
      information which is due to the collagen composition of the skin. SHG microscopy
      visualizes collagen fibers in the skin based on their SHG property. These two
      modalities have been applied to the same skin pathologies associated with
      collagen changes, but their relationship has not been examined. In this study, we
      tried to find the relationship by imaging the same skin samples with both
      modalities. Various parts of the normal rat skin and burn damaged skin were
      imaged ex vivo, and their images were analyzed both qualitatively and
      quantitatively. PS-OCT images were analyzed to obtain tissue birefringence. SHG
      images were analyzed to obtain collagen orientation indices by applying 2D
      Fourier transform. The skin samples having higher birefringence values had higher
      collagen orientation indices, and a linear correlation was found between them.
      Burn damaged skin showed decreases in both parameters compared to the control
      skins. This relationship between the bulk and microscopic properties of skin may
      be useful for further skin studies. 

PMID- 26203381
TI  - Subsurface ablation of atherosclerotic plaque using ultrafast laser pulses.
AB  - We perform subsurface ablation of atherosclerotic plaque using ultrafast pulses.
      Excised mouse aortas containing atherosclerotic plaque were ablated with
      ultrafast near-infrared (NIR) laser pulses. Optical coherence tomography (OCT)
      was used to observe the ablation result, while the physical damage was inspected
      in histological sections. We characterize the effects of incident pulse energy on
      surface damage, ablation hole size, and filament propagation. We find that it is
      possible to ablate plaque just below the surface without causing surface damage,
      which motivates further investigation of ultrafast ablation for subsurface
      atherosclerotic plaque removal. 

PMID- 26203382
TI  - Silicon photonic integrated circuit swept-source optical coherence tomography
      receiver with dual polarization, dual balanced, in-phase and quadrature
      detection.
AB  - Optical coherence tomography (OCT) is a widely used three-dimensional (3D)
      optical imaging method with many biomedical and non-medical applications.
      Miniaturization, cost reduction, and increased functionality of OCT systems will
      be critical for future emerging clinical applications. We present a silicon
      photonic integrated circuit swept-source OCT (SS-OCT) coherent receiver with dual
      polarization, dual balanced, in-phase and quadrature (IQ) detection. We
      demonstrate multiple functional capabilities of IQ polarization resolved
      detection including: complex-conjugate suppressed full-range OCT, polarization
      diversity detection, and polarization-sensitive OCT. To our knowledge, this is
      the first demonstration of a silicon photonic integrated receiver for OCT. The
      integrated coherent receiver provides a miniaturized, low-cost solution for SS
      OCT, and is also a key step towards a fully integrated high speed SS-OCT system
      with good performance and multi-functional capabilities. With further performance
      improvement and cost reduction, photonic integrated technology promises to
      greatly increase penetration of OCT systems in existing applications and enable
      new applications. 

PMID- 26203383
TI  - Correction of depth-induced spherical aberration for deep observation using two
      photon excitation fluorescence microscopy with spatial light modulator.
AB  - We demonstrate fluorescence imaging with high fluorescence intensity and depth
      resolution in which depth-induced spherical aberration (SA) caused by refractive
      index mismatch between the medium and biological sample is corrected. To reduce
      the impact of SA, we incorporate a spatial light modulator into a two-photon
      excitation fluorescence microscope. Consequently, when fluorescent beads in epoxy
      resin were observed with this method of SA correction, the fluorescence signal of
      the observed images was ~27 times higher and extension in the direction of the
      optical axes was ~6.5 times shorter at a depth of ~890 MUm. Thus, the proposed
      method increases the depth observable at high resolution. Further, our results
      show that the method improved the fluorescence intensity of images of the
      fluorescent beads and the structure of a biological sample. 

PMID- 26203384
TI  - Flux or speed? Examining speckle contrast imaging of vascular flows.
AB  - Speckle contrast imaging enables rapid mapping of relative blood flow
      distributions using camera detection of back-scattered laser light. However,
      speckle derived flow measures deviate from direct measurements of erythrocyte
      speeds by 47 +/- 15% (n = 13 mice) in vessels of various calibers. Alternatively,
      deviations with estimates of volumetric flux are on average 91 +/- 43%. We
      highlight and attempt to alleviate this discrepancy by accounting for the effects
      of multiple dynamic scattering with speckle imaging of microfluidic channels of
      varying sizes and then with red blood cell (RBC) tracking correlated speckle
      imaging of vascular flows in the cerebral cortex. By revisiting the governing
      dynamic light scattering models, we test the ability to predict the degree of
      multiple dynamic scattering across vessels in order to correct for the observed
      discrepancies between relative RBC speeds and multi-exposure speckle imaging
      estimates of inverse correlation times. The analysis reveals that traditional
      speckle contrast imagery of vascular flows is neither a measure of volumetric
      flux nor particle speed, but rather the product of speed and vessel diameter. The
      corrected speckle estimates of the relative RBC speeds have an average 10 +/- 3%
      deviation in vivo with those obtained from RBC tracking. 

PMID- 26203386
TI  - Directional migration of cancer cells induced by a blue light intensity gradient.
AB  - We used a spatial light modulator to project an optical micropattern of 473 nm
      light with a quartic intensity gradient on a single lung cancer cell. We observed
      that the intracellular amounts of reactive oxygen species (ROS) of the cancer
      cells were proportional to the intensity of the blue light, and the blue light
      intensity gradients could drive directional cell migration. This optically
      induced directional cell migration was inhibited by a ROS scavenger in the
      culture medium in a dose-dependent manner. In contrast, the ROS levels in
      fibroblasts were saturated by the blue light at low intensity and therefore the
      fibroblasts did not exhibit directional migration in the intensity gradient. 

PMID- 26203385
TI  - In-vivo multilaboratory investigation of the optical properties of the human
      head.
AB  - The in-vivo optical properties of the human head are investigated in the 600-1100
      nm range on different subjects using continuous wave and time domain diffuse
      optical spectroscopy. The work was performed in collaboration with different
      research groups and the different techniques were applied to the same subject.
      Data analysis was carried out using homogeneous and layered models and final
      results were also confirmed by Monte Carlo simulations. The depth sensitivity of
      each technique was investigated and related to the probed region of the cerebral
      tissue. This work, based on different validated instruments, is a contribution to
      fill the existing gap between the present knowledge and the actual in-vivo values
      of the head optical properties. 

PMID- 26203387
TI  - Optimization of advanced Wiener estimation methods for Raman reconstruction from
      narrow-band measurements in the presence of fluorescence background.
AB  - Raman spectroscopy has shown great potential in biomedical applications. However,
      intrinsically weak Raman signals cause slow data acquisition especially in Raman
      imaging. This problem can be overcome by narrow-band Raman imaging followed by
      spectral reconstruction. Our previous study has shown that Raman spectra free of
      fluorescence background can be reconstructed from narrow-band Raman measurements
      using traditional Wiener estimation. However, fluorescence-free Raman spectra are
      only available from those sophisticated Raman setups capable of fluorescence
      suppression. The reconstruction of Raman spectra with fluorescence background
      from narrow-band measurements is much more challenging due to the significant
      variation in fluorescence background. In this study, two advanced Wiener
      estimation methods, i.e. modified Wiener estimation and sequential weighted
      Wiener estimation, were optimized to achieve this goal. Both spontaneous Raman
      spectra and surface enhanced Raman spectra were evaluated. Compared with
      traditional Wiener estimation, two advanced methods showed significant
      improvement in the reconstruction of spontaneous Raman spectra. However,
      traditional Wiener estimation can work as effectively as the advanced methods for
      SERS spectra but much faster. The wise selection of these methods would enable
      accurate Raman reconstruction in a simple Raman setup without the function of
      fluorescence suppression for fast Raman imaging. 

PMID- 26203388
TI  - X-ray luminescence computed tomography imaging based on X-ray distribution model
      and adaptively split Bregman method.
AB  - X-ray luminescence computed tomography (XLCT) has become a promising imaging
      technology for biological application based on phosphor nanoparticles. There are
      mainly three kinds of XLCT imaging systems: pencil beam XLCT, narrow beam XLCT
      and cone beam XLCT. Narrow beam XLCT can be regarded as a balance between the
      pencil beam mode and the cone-beam mode in terms of imaging efficiency and image
      quality. The collimated X-ray beams are assumed to be parallel ones in the
      traditional narrow beam XLCT. However, we observe that the cone beam X-rays are
      collimated into X-ray beams with fan-shaped broadening instead of parallel ones
      in our prototype narrow beam XLCT. Hence we incorporate the distribution of the X
      ray beams in the physical model and collected the optical data from only two
      perpendicular directions to further speed up the scanning time. Meanwhile we
      propose a depth related adaptive regularized split Bregman (DARSB) method in
      reconstruction. The simulation experiments show that the proposed physical model
      and method can achieve better results in the location error, dice coefficient,
      mean square error and the intensity error than the traditional split Bregman
      method and validate the feasibility of method. The phantom experiment can obtain
      the location error less than 1.1 mm and validate that the incorporation of fan
      shaped X-ray beams in our model can achieve better results than the parallel X
      rays. 

PMID- 26203389
TI  - Wide-field in vivo oral OCT imaging.
AB  - We have built a polarization-sensitive swept source Optical Coherence Tomography
      (OCT) instrument capable of wide-field in vivo imaging in the oral cavity. This
      instrument uses a hand-held side-looking fiber-optic rotary pullback catheter
      that can cover two dimensional tissue imaging fields approximately 2.5 mm wide by
      up to 90 mm length in a single image acquisition. The catheter spins at 100 Hz
      with pullback speeds up to 15 mm/s allowing imaging of areas up to 225 mm(2)
      field-of-view in seconds. A catheter sheath and two optional catheter sheath
      holders have been designed to allow imaging at all locations within the oral
      cavity. Image quality of 2-dimensional image slices through the data can be
      greatly enhanced by averaging over the orthogonal dimension to reduce speckle.
      Initial in vivo imaging results reveal a wide-field view of features such as
      epithelial thickness and continuity of the basement membrane that may be useful
      in clinic for chair-side management of oral lesions. 

PMID- 26203390
TI  - Erratum: Raman difference spectroscopy: a non-invasive method for identification
      of oral squamous cell carcinoma: publisher's note.
AB  - The author list appeared incorrectly in [Biomed. Opt. Express 5(9), 3252-3265
      (2014)]. The author names were corrected online as of January 17, 2015:
      https://www.osapublishing.org/boe/abstract.cfm?uri=boe-5-9-3252.[This corrects
      the article on p. 3252 in vol. 5, PMID: 25401036.].

PMID- 26203391
TI  - Verification of the lack of correlation between age and longitudinal chromatic
      aberrations of the human eye from the visible to the infrared.
AB  - Several researchers studied the longitudinal chromatic aberration (LCA) of the
      human eye and observed that it does not change due to age. We measured the LCA of
      45 subjects' normal right eyes at three distinct wavelengths (561, 690, and 840
      nm) using a Hartmann-Shack wavefront aberrometer (HSWA) while consecutively
      switching between three light sources for wavefront sensing. We confirmed that
      the LCA of the human eye does not change due to age between 22 and 57 years. 

PMID- 26203392
TI  - Non-contact scanning diffuse correlation tomography system for three-dimensional
      blood flow imaging in a murine bone graft model.
AB  - A non-contact galvanometer-based optical scanning system for diffuse correlation
      tomography was developed for monitoring bone graft healing in a murine femur
      model. A linear image reconstruction algorithm for diffuse correlation tomography
      was tested using finite-element method based simulated data and experimental data
      from a femur or a tube suspended in a homogeneous liquid phantom. Finally, the
      non-contact system was utilized to monitor in vivo blood flow changes prior to
      and one week after bone graft transplantation within murine femurs. Localized
      blood flow changes were observed in three mice, demonstrating a potential for
      quantification of longitudinal blood flow associated with bone graft healing. 

PMID- 26203393
TI  - High-resolution three-dimensional in vivo imaging of mouse oviduct using optical
      coherence tomography.
AB  - The understanding of the reproductive events and the molecular mechanisms
      regulating fertility and infertility in humans relies heavily on the analysis of
      the corresponding phenotypes in mouse models. While molecular genetic approaches
      provide significant insight into the molecular regulation of these processes, the
      lack of live imaging methods that allow for detailed visualization of the mouse
      reproductive organs limits our investigations of dynamic events taking place
      during the ovulation, the fertilization and the pre-implantation stages of
      embryonic development. Here we introduce an in vivo three-dimensional imaging
      approach for visualizing the mouse oviduct and reproductive events with micro
      scale spatial resolution using optical coherence tomography (OCT). This method
      relies on the natural tissue optical contrast and does not require the
      application of any contrast agents. For the first time, we present live high
      resolution images of the internal structural features of the oviduct, as well as
      other reproductive organs and the oocytes surrounded by cumulus cells. These
      results provide the basis for a wide range of live dynamic studies focused on
      understanding fertility and infertility. 

PMID- 26203394
TI  - Can Medical Decision-making at the Scene by EMS Staff Reduce the Number of
      Unnecessary Ambulance Transportations, but Still Be Safe?
AB  - OBJECTIVES: The aim of this study was to evaluate the procedures adopted by the
      staff of the Shiraz Emergency Medical Services (EMS) and the outcome of the
      patients discharged from the scene over a one-year period.   BACKGROUND:
      Unnecessary use of ambulances results in the overloading of EMS and the over
      crowding of emergency departments. Medical assessment at the scene by EMS staff
      may reduce these issues. In an earlier study in Shiraz, 36% of the patients were
      left at home/discharged directly from the scene with or without treatment by EMS
      staff after consulting a physician at the dispatch center. However, there has
      been no evaluation of this system with regard to mortality and morbidity.  
      MATERIALS AND METHODS: Retrospective data on all missions performed by the Shiraz
      EMS (2012-2013) were reviewed. All the patients discharged from the scene by the
      EMS staff on the 5th, 15th, and 25th days of each month were included. A
      questionnaire with nine questions was designed, and available patients/relatives
      were interviewed prospectively (2014; follow-up period 4-12 months).   RESULTS:
      Out of 3019 cases contacted, 994 (almost 33%) replied. There were 26%-93%
      reductions in the complaints in all disease categories. A group of the patients
      left the scene at their own will. Of those who were discharged by the EMS staff
      at the scene, over 60% were without any complaints. Twelve out of 253 patients
      died after they were sent home by the EMS staff.   CONCLUSIONS: Patients may be
      discharged at the scene by EMS staff and after consulting a physician. However,
      there is a need for a solid protocol to ensure total patient safety. This calls
      for a prospective study.

PMID- 26203395
TI  - Twitter as a Potential Disaster Risk Reduction Tool. Part I: Introduction,
      Terminology, Research and Operational Applications.
AB  - Twitter, a popular communications platform, is identified as contributing to
      improved mortality and morbidity outcomes resulting from the 2013 Hattiesburg,
      Mississippi EF-4 Tornado. This study describes the methodology by which Twitter
      was investigated as a potential disaster risk reduction and management tool at
      the community level and the process by which the at-risk population was
      identified from the broader Twitter user population. By understanding how various
      factors contribute to the superspreading of messages, one can better optimize
      Twitter as an essential communications and risk reduction tool. This study
      introduces Parts II, III and IV which further define the technological and
      scientific knowledge base necessary for developing future competency base
      curriculum and content for Twitter assisted disaster management education and
      training at the community level. 

PMID- 26203396
TI  - Twitter as a Potential Disaster Risk Reduction Tool. Part II: Descriptive
      Analysis of Identified Twitter Activity during the 2013 Hattiesburg F4 Tornado.
AB  - BACKGROUND: This article describes a novel triangulation methodological approach
      for identifying twitter activity of regional active twitter users during the 2013
      Hattiesburg EF-4 Tornado. METHODOLOGY: A data extraction and geographically
      centered filtration approach was utilized to generate Twitter data for 48 hrs pre
      and post-Tornado. The data was further validated using six sigma approach
      utilizing GPS data. RESULTS: The regional analysis revealed a total of 81,441
      tweets, 10,646 Twitter users, 27,309 retweets and 2637 tweets with GPS
      coordinates. CONCLUSIONS: Twitter tweet activity increased 5 fold during the
      response to the Hattiesburg Tornado.  Retweeting activity increased 2.2 fold.
      Tweets with a hashtag increased 1.4 fold. Twitter was an effective disaster risk
      reduction tool for the Hattiesburg EF-4 Tornado 2013.

PMID- 26203397
TI  - Twitter as a Potential Disaster Risk Reduction Tool. Part III: Evaluating
      Variables that Promoted Regional Twitter Use for At-risk Populations During the
      2013 Hattiesburg F4 Tornado.
AB  - INTRODUCTION: Study goals attempt to identify the variables most commonly
      associated with successful tweeted messages and determine which variables have
      the most influence in promoting exponential dissemination of information (viral
      spreading of the message) and trending (becoming popular) in the given disaster
      affected region. METHODS: Part II describes the detailed extraction and
      triangulation filtration methodological approach to acquiring twitter data for
      the 2013 Hattiesburg Tornado. The data was then divided into two 48 hour windows
      before and after the tornado impact with a 2 hour pre-tornado buffer to capture
      tweets just prior to impact. Criteria-based analysis was completed for Tweets and
      users. The top 100 pre-Tornado and post-Tornado retweeted users were compared to
      establish the variability among the top retweeted users during the 4 day span. 
      RESULTS: Pre-Tornado variables that were correlated to higher retweeted rates
      include total user tweets (0.324), and total times message retweeted (0.530). 
      Post-Tornado variables that were correlated to higher retweeted rates include
      total hashtags in a retweet (0.538) and hashtags #Tornado (0.378) and
      #Hattiesburg (0.254). Overall hashtags usage significantly increased during the
      storm. Pre-storm there were 5,763 tweets with a hashtag and post-storm there was
      13,598 using hashtags. CONCLUSIONS: Twitter's unique features allow it to be
      considered a unique social media tool applicable for emergency managers and
      public health officials for rapid and accurate two way communication. 
      Additionally, understanding how variables can be properly manipulated plays a key
      role in understanding how to use this social media platform for effective,
      accurate, and rapid mass information communication.

PMID- 26203398
TI  - Twitter as a Potential Disaster Risk Reduction Tool. Part IV: Competency-based
      Education and Training Guidelines to Promote Community Resiliency.
AB  - Twitter can be an effective tool for disaster risk reduction but gaps in
      education and training exist in current public health and disaster management
      educational competency standards.  Eleven core public health and disaster
      management competencies are proposed that incorporate Twitter as a tool for
      effective disaster risk reduction.  Greater funding is required to promote the
      education and training of this tool for those in professional schools and in the
      current public health and disaster management workforce. 

PMID- 26203399
TI  - Support Needs for Canadian Health Providers Responding to Disaster: New Insights
      from a Grounded Theory Approach.
AB  - INTRODUCTION: An earlier descriptive study exploring the various supports
      available to Canadian health and social service providers who deployed to the
      2010 earthquake disaster in Haiti, indicated that when systems are compromised,
      professionals are at physical, emotional and mental risk during overseas
      deployment. While these risks are generally well-identified, there is little
      literature that explores the effectiveness of the supports in place to mitigate
      this risk. This study provides evidence to inform policy development regarding
      future disaster relief, and the effectiveness of supports available to responders
      assisting with international disaster response. METHODS: This study follows
      Strauss and Corbin's 1990 structured approach to grounded theory to develop a
      framework for effective disaster support systems. N=21 interviews with Canadian
      health and social service providers, who deployed to Haiti in response to the
      2010 earthquake, were conducted and analyzed. Resulting data were transcribed,
      coded and analysed for emergent themes. RESULTS AND DISCUSSION: Three themes were
      identified in the data and were used to develop the evolving theory. The
      interview data indicate that the experiences of responders are determined based
      on an interaction between the individual's 'lens' or personal expectations, as
      well as the supports that an organization is able to provide. Therefore,
      organizations should consider the following factors: experience, expectations,
      and supports, to tailor a successful support initiative that caters to the needs
      of the volunteer workforce.

PMID- 26203400
TI  - Application of Behavioral Theories to Disaster and Emergency Health Preparedness:
      A Systematic Review.
AB  - BACKGROUND: Preparedness for disasters and emergencies at individual, community
      and organizational levels could be more effective tools in mitigating (the
      growing incidence) of disaster risk and ameliorating their impacts. That is, to
      play more significant roles in disaster risk reduction (DRR). Preparedness
      efforts focus on changing human behaviors in ways that reduce people's risk and
      increase their ability to cope with hazard consequences. While preparedness
      initiatives have used behavioral theories to facilitate DRR, many theories have
      been used and little is known about which behavioral theories are more commonly
      used, where they have been used, and why they have been preferred over
      alternative behavioral theories. Given that theories differ with respect to the
      variables used and the relationship between them, a systematic analysis is an
      essential first step to answering questions about the relative utility of
      theories and providing a more robust evidence base for preparedness components of
      DRR strategies. The goal of this systematic review was to search and summarize
      evidence by assessing the application of behavioral theories to disaster and
      emergency health preparedness across the world. METHODS: The protocol was
      prepared in which the study objectives, questions, inclusion and exclusion
      criteria, and sensitive search strategies were developed and pilot-tested at the
      beginning of the study. Using selected keywords, articles were searched mainly in
      PubMed, Scopus, Mosby's Index (Nursing Index) and Safetylit databases. Articles
      were assessed based on their titles, abstracts, and their full texts. The data
      were extracted from selected articles and results were presented using
      qualitative and quantitative methods. RESULTS: In total, 2040 titles, 450
      abstracts and 62 full texts of articles were assessed for eligibility criteria,
      whilst five articles were archived from other sources, and then finally, 33
      articles were selected. The Health Belief Model (HBM), Extended Parallel Process
      Model (EPPM), Theory of Planned Behavior (TPB) and Social Cognitive Theories were
      most commonly applied to influenza (H1N1 and H5N1), floods, and earthquake
      hazards. Studies were predominantly conducted in USA (13 studies). In Asia, where
      the annual number of disasters and victims exceeds those in other continents,
      only three studies were identified. Overall, the main constructs of HBM
      (perceived susceptibility, severity, benefits, and barriers), EPPM (higher threat
      and higher efficacy), TPB (attitude and subjective norm), and the majority of the
      constructs utilized in Social Cognitive Theories were associated with
      preparedness for diverse hazards. However, while all the theories described above
      describe the relationships between constituent variables, with the exception of
      research on Social Cognitive Theories, few studies of other theories and models
      used path analysis to identify the interdependence relationships between the
      constructs described in the respective theories/models. Similarly, few identified
      how other mediating  variables could influence disaster and emergency
      preparedness.  CONCLUSIONS: The existing evidence on the application of
      behavioral theories and models to disaster and emergency preparedness is chiefly
      from developed countries. This raises issues regarding their utility in
      countries, particularly in Asisa and the Middle East, where cultural
      characteristics are very different to those prevailing in the Western countries
      in which theories have been developed and tested. The theories and models
      discussed here have been applied predominantly to disease outbreaks and natural
      hazards, and information on their utility as guides to preparedness for man-made
      hazards is lacking. Hence, future studies related to behavioral theories and
      models addressing preparedness need to target developing countries where disaster
      risk  and the consequent need for preparedness is high. A need for additional
      work on demonstrating the relationships of variables and constructs, including
      more clearly articulating roles for mediating effects was also identified in this
      analysis.

PMID- 26203402
TI  - Mutation in GM2A Leads to a Progressive Chorea-dementia Syndrome.
AB  - BACKGROUND: The etiology of many cases of childhood-onset chorea remains
      undetermined, although advances in genomics are revealing both new disease
      associated genes and variant phenotypes associated with known genes. METHODS: We
      report a Saudi family with a neurodegenerative course dominated by progressive
      chorea and dementia in whom we performed homozygosity mapping and whole exome
      sequencing. RESULTS: We identified a homozygous missense mutation in GM2A within
      a prominent block of homozygosity. This mutation is predicted to impair protein
      function. DISCUSSION: Although discovered more than two decades ago, to date,
      only five patients with this rare form of GM2 gangliosidosis have been reported.
      The phenotype of previously described GM2A patients has been typified by onset in
      infancy, profound hypotonia and impaired volitional movement, intractable
      seizures, hyperacusis, and a macular cherry red spot. Our findings expand the
      phenotypic spectrum of GM2A mutation-positive gangliosidosis to include
      generalized chorea without macular findings or hyperacusis and highlight how
      mutations in neurodegenerative disease genes may present in unexpected ways.

PMID- 26203403
TI  - Combined Endonasal-Transcervical Approach to a Metastatic Parapharyngeal Space
      Papillary Thyroid Carcinoma.
AB  - PURPOSE:  Although papillary thyroid carcinoma metastases to the parapharyngeal
      space are rare, the high amount of fat tissue allows tumors to grow clinically
      undetectable until they invade most of the parapharyngeal space. We describe for
      the first time a combined endonasal and transcervical approach for a
      parapharyngeal metastasis from a papillary thyroid carcinoma. MATERIALS AND
      METHODS:  A 51-year-old male with a previous history of papillary thyroid
      carcinoma presented with left ear fullness and left-sided facial numbness.
      Imaging revealed a 4x3 cm pre-styloid parapharyngeal space mass invading the
      foramen ovale and extending below the palate. Needle biopsy confirmed metastatic
      papillary thyroid carcinoma. RESULTS:  The lesion was resected with a combined
      endoscopic endonasal and transcervical approach. Postoperative MRI revealed gross
      total resection, and the patient recovered from his symptoms. CONCLUSION:  This
      novel approach provides access to pre-styloid parapharyngeal tumors with superior
      extension to the skull base, avoiding more extensive traditional open approaches.

PMID- 26203404
TI  - Correlation of Foraminal Area and Response to Cervical Nerve Root Injections.
AB  - INTRODUCTION: Patients with age-related degenerative changes in the cervical
      spine leading to cervical spondylosis may be symptomatic or asymptomatic. Older
      patients with radicular pain tend to have a better response to epidural steroid
      injections, but it is often difficult to predict which patients will have a
      positive response to selective nerve root block (SNRB). We analyzed whether the
      cervical neuroforaminal area measured on MRI predicts immediate therapeutic
      responses to SNRB in patients who have cervical radiculopathy. METHODS: We
      retrospectively reviewed all patients who had cervical SNRBs treated at a single
      tertiary referral center. We recorded patient demographics, the neuroforaminal
      area of the symptomatic and contralateral sides, Visual Analog Scale (VAS) score
      pre- and post-injection, history of previous cervical surgery, comorbidities, and
      history of tobacco use. RESULTS: Sixty-four patients with symptoms of cervical
      radiculopathy treated with neuroforaminal nerve root injections had appropriate
      imaging and VAS scores recorded. The average foraminal area of the symptomatic
      side before treatment was significantly smaller than the contralateral
      asymptomatic neuroforamen (p<0.0001). Those patients with the smallest
      neuroforamen had a positive response to SNRB. Diabetes and tobacco use did not
      influence patient response to treatment. CONCLUSIONS: Measurement of
      neuroforaminal areas on MRI may represent a useful pre-procedural technique to
      predict which patients with symptoms of cervical radiculopathy secondary to
      foraminal stenosis are likely to respond to selective nerve root injections. The
      predictive ability appears to be limited to those patients with severe stenosis
      and was less useful in those patients with moderate or mild stenosis.

PMID- 26203401
TI  - Unconventional Neurogenic Niches and Neurogenesis Modulation by Vitamins.
AB  - Although the generation of new neurons occurs in adult mammals, it has been
      classically described in two defined regions of the brain denominated neurogenic
      niches: the subventricular zone of the lateral ventricles and the subgranular
      zone of the dentate gyrus. In these regions, neural stem cells give rise to new
      neurons and glia, which functionally integrate into the existing circuits under
      physiological conditions. However, accumulating evidence indicates the presence
      of neurogenic potential in other brain regions, from which multipotent precursors
      can be isolated and differentiated in vitro. In some of these regions, neuron
      generation occurs at low levels; however, the addition of growth factors,
      hormones or other signaling molecules increases the proliferation and
      differentiation of precursor cells. In addition, vitamins, which are
      micronutrients necessary for normal brain development, and whose deficiency
      produces neurological impairments, have a regulatory effect on neural stem cells
      in vitro and in vivo. In the present review, we will describe the progress that
      has been achieved in determining the neurogenic potential in other regions, known
      as unconventional niches, as well as the characteristics of the neural stem cells
      described for each region. Finally, we will revisit the roles of commonly known
      vitamins as modulators of precursor cell proliferation and differentiation, and
      their role in the complex and tight molecular signaling that impacts these
      neurogenic niches.

PMID- 26203405
TI  - The Sun-Earth connect 3: lessons from the periodicities of deep time influencing
      sea-level change and marine extinctions in the geological record.
AB  - A number of papers since Rampino and Stothers published in Science 1984 have
      reported common periodicities in a wide range of climate, geomagnetic, tectonic
      and biological proxies, including marine extinctions. Single taper and multitaper
      spectral analysis of marine fluctuations between the Late Cretaceous and the
      Miocene replicates a number of the published harmonics. Whereas these common
      periodicities have been argued to have a galactic origin, this paper presents an
      alternative fractal model based on large scale fluctuations of the magnetic field
      of the Sun. The fluctuations follow a self-similar matrix of periodicities and
      the solutions of the differential equation allow for models to be constructed
      predicting extreme events for solar emissions. A comparison to major Phanerozoic
      extinction, climate and geomagnetic events, captured in the geological record,
      show a striking loop symmetry summarised in major 66 Ma irradiance and
      electromagnetic pulses from the Sun. 

PMID- 26203406
TI  - Signal parameter estimation of complex exponentials using fourth order
      statistics: additive Gaussian noise environment.
AB  - A novel approach based on fourth order statistics is presented for estimating the
      parameters of the complex exponential signal model in additive colored Gaussian
      noise whose autocorrelation function is not known. Monte Carlo simulations
      demonstrate that the proposed method performs better than an existing method
      which also utilizes fourth order statistics under the similar noise condition. To
      deal with the non-stationarity of the modeled signal, various concepts are
      introduced while extending the estimation technique based on linear prediction to
      the higher order statistics domain. It is illustrated that the accuracy of
      parameter estimation in this case improves due to better handling of signal non
      stationarity. While forming the fourth order moment/ cumulant of a signal, the
      choice of the lag-parameters is crucial. It has been demonstrated that the
      symmetric fourth order moment/ cumulant as defined in this paper will have many
      desirable properties. 

PMID- 26203407
TI  - Exact solution to the problem of N bodies forming a multi-layer rotating
      structure.
AB  - Exact solutions to the problem of the Newtonian gravitational interaction of N
      material points moving around N 2 concentric circular orbits are considered. Each
      circular orbit contains N 3 axisymmetrically located bodies having identical
      masses. The structure as a whole rotates around its symmetry axis. Such
      structures are identical to the homographic-dynamics configurations, or planar
      central configurations, known from literature. Conceptually, those structures can
      be considered as structures formed by mutually embedded polygons with point
      bodies placed at polygon vortices. For structures involving less than 20 bodies,
      solutions were obtained using Hamiltonian-mechanics methods. In the study, the
      forces acting on each body in the rotating structure from the side of all other
      bodies were found. The differential motion equations of the bodies were reduced
      to a system of linear algebraic equations for the body masses. Solutions in
      various forms were obtained. For specifying the initial parameters and for
      calculating all other characteristics of the structures, a computer program
      RtCrcSt2.for has been developed. Structures comprising up to one million bodies
      have been calculated. Graphical images of obtained structures are presented, and
      their properties are described. Stability problems for examined structures are
      considered, and possible application of obtained results to celestial- and space
      mechanics problems is discussed. 

PMID- 26203408
TI  - Unusual skin manifestation of hand, foot and mouth disease associated with
      coxsackievirus A6: cases report.
AB  - BACKGROUND: Hand, food, and mouth disease (HFMD) is a highly contagious disease
      caused by enteroviruses infection. It is a health problem in young children under
      5 years of age worldwide. The common causative agents are coxsackievirus A 16
      (CA16) and enterovirus 71 (EV71). In recent years, coxsackievirus A6 (CA6) has
      emerged to be one of the major etiologic agents of HFMD worldwide including in
      Thailand. CASE DESCRIPTION: We reported cases with unusual skin manifestations of
      CA6-associated HFMD such as widespread severe cutaneous eruption, large vesicles
      (varicelliform), purpuric-like lesions or Gianotti-Crosti like eruptions.
      DISCUSSION AND EVALUATION: Molecular characterization of the CA6 strains from
      those patients found that all were clustered in the same group of CA6 that are
      currently circulating in Thailand. CONCLUSIONS: Clinicians need to be aware of
      the expanded range of cutaneous findings in CA6-associated HFMD in order to
      properly consider the diagnosis, management and prevention.

PMID- 26203409
TI  - Epidural anesthesia for laparoscopic bariatric surgery: a case report.
AB  - BACKGROUND: Rapid and uneventful postoperative recovery following general
      anesthesia in morbidly obese patients undergoing bariatric surgery may offer
      challenges to anesthesiologists. With improved surgical techniques and shorter
      pneumoperitoneum, regional anesthesia may be considered for this laparoscopic
      procedure in selected cases. CASE DESCRIPTION: The first patient was a 60-year
      old male (body mass index: 39 kg/m(2)) who was scheduled for laparoscopic sleeve
      gastrectomy. The second patient was a 46-year-old female (body mass index: 47
      kg/m(2)) who was scheduled for laparoscopic gastric bypass. After standard
      intraoperative monitoring was applied, epidural anesthesia was performed at
      thoracic level T9-T10. Surgical technique modification included insufflation of
      CO2 at a low flow rate and avoidance of orogastric tube use. During the
      procedure, both patients breathed spontaneously without difficulty. One
      hypotension episode occurred and was successfully treated with a 12-mg bolus of
      ephedrine in case 1. Shoulder pain occurred intraoperatively in case 2 and was
      successfully treated with a 50-MUg bolus of fentanyl. Postoperatively, 2 mg
      epidural morphine was administered for postoperative analgesia. Both patients
      were satisfied with the anesthesia technique and was discharged uneventfully.
      DISCUSSION AND EVALUATION: This anesthetic technique may maintain pre-operative
      respiratory function, increase alertness, and reduce the use of rescue
      analgesics, which is crucial for optimal outcomes in morbidly obese patients.
      Conversion of epidural anesthesia to general anesthesia may be required if
      patients can not tolerate the laparoscopic procedure (e.g. intolerable shoulder
      pain) or the increased respiratory rate during pneumoperitoneum leading to
      difficulty in performing laparoscopic surgery. Further studies are needed to
      elucidate this issue. CONCLUSIONS: General anesthesia is widely used for
      laparoscopic bariatric surgery, but epidural anesthesia may be a viable
      alternative to general anesthesia in selected cases. Further prospective studies
      may be required to elucidate the relative advantages and disadvantages of
      epidural anesthesia in this surgical population.

PMID- 26203411
TI  - Efficacy of a Process Improvement Intervention on Inmate Awareness of HIV
      Services: A Multi-Site Trial.
AB  - The prevalence of HIV among U.S. inmates is much greater than in the general
      population, creating public health concerns and cost issues for the criminal
      justice system. The HIV Services and Treatment Implementation in Corrections
      protocol of the NIDA funded Criminal Justice Drug Abuse Treatment Studies
      cooperative tested the efficacy of an organizational process improvement strategy
      on improving HIV services in correctional facilities. For this paper, we analyzed
      efficacy of this strategy on improving inmate awareness and perceptions of HIV
      services. The study used a multi-site (n=28) clustered randomized trial approach.
      Facilities randomized to the experimental condition used a coach-driven local
      change team approach to improve HIV services at their facility. Facilities in the
      control condition were given a directive to improve HIV services on their own.
      Surveys about awareness and perceptions of HIV services were administered
      anonymously to inmates who were incarcerated in study facilities at baseline
      (n=1253) and follow-up (n=1048). A series of one-way ANOVAs were run to test
      whether there were differences between inmates in the experimental and control
      facilities at baseline and follow-up. Differences were observed at baseline, with
      the experimental group having significantly lower scores than the control group
      on key variables. But, at post-test, following the intervention, these
      differences were no longer significant. Taken in context of the findings from the
      main study, these results suggest that the change team approach to improving HIV
      services in correctional facilities is efficacious for improving inmates'
      awareness and perceptions of HIV services.

PMID- 26203410
TI  - Optimization of time to initial vancomycin target trough improves clinical
      outcomes.
AB  - BACKGROUND: Outcomes data for the efficacy of interventions designed to decrease
      the time to initial target vancomycin troughs are sparse. OBJECTIVE: A vancomycin
      therapeutic drug monitoring (TDM) program was initiated to reduce the time to
      initial target troughs and to examine the impact on clinical outcomes. METHODS:
      Single-center, pre- and post-intervention observational study in a 250 bed
      teaching facility. Adult inpatients treated with physician-guided, vancomycin
      therapy (historical control, CTRL) were compared to high trough, pharmacist
      guided vancomycin therapy (TDM). Nephrotoxicity analyses were conducted to the
      ensure safety of the TDM. Clinical outcome analysis was limited to patients with
      normal renal function and culture-confirmed gram positive infections and a pre
      defined MRSA subset. RESULTS: 340 patients met initial inclusion criteria for the
      nephrotoxicity analysis (TDM, n = 173; CTRL, n = 167). Acute kidney injury
      occurrence was similar between the CTRL (n = 20) and TDM (n = 23) groups (p =
      0.7). Further exclusions yielded 145 patients with gram positive infections for
      clinical outcomes evaluation (TDM, n = 66; CTRL, n = 75). The time to initial
      target trough was shorter in the TDM group (3 vs. 5 days, p < 0.001). Patients in
      the TDM group discharged from the hospital more rapidly, 7 vs. 14 days (Hazards
      Ratio (HR), 1.41; 95% Confidence Interval [CI] 1.08-1.83; p = 0.01), reached
      clinical stability faster, 4 vs. 8 days (HR, 1.51; 95% CI 1.08-2.11; p = 0.02),
      and had shorter courses of vancomycin, 4 vs. 7 days (HR, 1.5; 95% CI 1.15-1.95; p
      = 0.003). In the MRSA infection subset (TDM, n = 36; CTRL, n = 35), patients in
      the TDM group discharged from the hospital more rapidly, 7 vs. 16 days (HR, 1.89;
      95% CI 1.08-3.3; p = 0.03), reached clinical stability faster, 4 vs. 6 days (HR,
      2.69; 95% CI 1.27-5.7; p = 0.01), and had shorter courses of vancomycin, 5 vs. 8
      days (HR, 2.52; 95% CI 1.38-4.6; p = 0.003). Attaining initial target troughs in
      <5 days versus >=5 days was associated with improved clinical outcomes. All cause
      in-hospital mortality, and vancomycin treatment failure occurred at comparable
      rates between groups. CONCLUSIONS: Interventions designed to decrease the time to
      reach initial target vancomycin troughs can improve clinical outcomes in gram
      positive infections, and in particular MRSA infections.

PMID- 26203412
TI  - Calocybella, a new genus for Rugosomyces pudicus (Agaricales, Lyophyllaceae) and
      emendation of the genus Gerhardtia.
AB  - Calocybella is a new genus established to accommodate Rugosomyces pudicus.
      Phylogenetic analyses based on a LSU-ITS sequence dataset place Calocybella
      sister to Gerhardtia from which it differs morphologically in the presence of
      clamp-connections and reddening context. The genus Gerhardtia is emended to also
      include taxa with smooth spores. According to our morphological analysis of
      voucher material, Calocybe juncicola s. auct. is shown to be Calocybella pudica. 

PMID- 26203413
TI  - Phylogenetic and microscopic studies in the genus Lactifluus (Basidiomycota,
      Russulales) in West Africa, including the description of four new species.
AB  - Despite the crucial ecological role of lactarioid taxa (Lactifluus, Lactarius) as
      common ectomycorrhiza formers in tropical African seasonal forests, their current
      diversity is not yet adequately assessed. During the last few years, numerous
      lactarioid specimens have been sampled in various ecosystems from Togo (West
      Africa). We generated 48 ITS sequences and aligned them against lactarioid taxa
      from other tropical African ecozones (Guineo-Congolean evergreen forests,
      Zambezian miombo). A Maximum Likelihood phylogenetic tree was inferred from a
      dataset of 109 sequences. The phylogenetic placement of the specimens, combined
      with morpho-anatomical data, supported the description of four new species from
      Togo within the monophyletic genus Lactifluus: within subgen. Lactifluus (L.
      flavellus), subgen. Russulopsis (L. longibasidius and L. pectinatus), and subgen.
      Edules (L. melleus). This demonstrates that the current species richness of the
      genus is considerably higher than hitherto estimated for African species and, in
      addition, a need to redefine the subgenera and sections within it. 

PMID- 26203415
TI  - The mycological legacy of Elias Magnus Fries.
AB  - The taxonomic concepts which originated with or were accepted by Elias Magnus
      Fries were presented during his lifetime in the printed word, illustrative
      depiction, and in collections of dried specimens. This body of work was welcomed
      by the mycological and botanical communities of his time: students and associates
      aided Fries and after his passing carried forward his taxonomic ideas. His legacy
      spawned a line of Swedish and Danish mycologists intent on perpetuating the Fries
      tradition: Hampus von Post, Lars Romell, Seth Lundell and John Axel Nannfeldt in
      Sweden; Emil Rostrup, Severin Petersen and Jakob Lange in Denmark. Volumes of
      color paintings and several exsiccati, most notably one edited by Lundell and
      Nannfeldt attached fungal portraits and preserved specimens (and often
      photographs) to Fries names. The result is a massive resource from which to
      harvest the name-concept relationship with clarity. In the 20th century,
      nomenclatural commissions legislated Fries's Systema and Elenchus as the
      "starting point" for names of most fungi, giving these books special recognition.
      The present paper attempts to trace Fries's legacy from his lifetime to the
      recent past. 

PMID- 26203414
TI  - Cercosporoid fungi (Mycosphaerellaceae) 3. Species on monocots (Poaceae, true
      grasses).
AB  - The third part of a series of monographic treatments of cercosporoid fungi
      (formerly Cercospora s. lat., Mycosphaerellaceae, Ascomycota) continues with a
      treatment of taxa on monocots (Liliopsida; Equisetopsida, Magnoliidae, Lilianae),
      covering asexual and holomorph species with mycosphaerella-like sexual morphs on
      true grasses (Poaceae), which were excluded from the second part. The species
      concerned are keyed out, alphabetically listed, described, illustrated and
      supplemented by references to previously published descriptions, illustrations,
      and exsiccatae. A key to the recognised genera and a discussion of taxonomically
      relevant characters was published in the first part of this series. Several
      species are lecto- or neotypified. The following taxonomic novelties are
      introduced: Cercospora barretoana comb. nov., C. cymbopogonicola nom. nov.,
      Cladosporium elymi comb. nov., Passalora agrostidicola sp. nov., P. brachyelytri
      comb. nov., and P. dichanthii-annulati comb. nov. 

PMID- 26203416
TI  - Australasian Sequestrate Fungi 19: Hysterangium colossum sp. nov.
AB  - Hysterangium colossum sp. nov., with extraordinarily large basidiomata for the
      genus, is described from dry Eucalyptus woodlands in the Australian Capital
      Territory and southeastern New South Wales. It typically grows in confluent
      clusters and has a thick peridium often invaginated into the gleba. 

PMID- 26203417
TI  - The lentinoid fungi (Lentinus and Panus) from Western Ghats, India.
AB  - Panus natarajanus sp. nov. from the Western Ghats of Karnataka, India, is
      described, illustrated and discussed along with P. velutinus, P. tephroleucus, P.
      ciliatus, P. hookerianus, Lentinus fasciatus, L. concentricus, and L.
      megacystidiatus. Lentinus alpacus is re-allocated to Panus as P. alpacus comb.
      nov., and contrasted with P. parvus. A short description with illustrations is
      provided of L. concinnus, which is also newly reported from the Western Ghats. A
      synoptic key for all species of lentinoid fungi of the Western Ghats is provided.

PMID- 26203419
TI  - Harorepupu aotearoa (Onygenales) gen. sp. nov.; a threatened fungus from shells
      of Powelliphanta and Paryphanta snails (Rhytididae).
AB  - A cleistothecial fungus, known only from the shells of giant land snails of the
      family Rhytidae, is described as a new genus and species within Onygenales,
      Harorepupu aotearoa gen. sp. nov. Known only from the sexual morph, this fungus
      is characterized morphologically by a membranous ascoma with no appendages and
      ascospores with a sparse network of ridges. Ribosomal DNA sequences place the new
      species within Onygenales, but comparison with the known genetic diversity within
      the order linked it to no existing genus or family. It is the first species of
      Onygenales reported from the shells of terrestrial snails. This fungus has been
      listed as Critically Endangered in New Zealand and has been previously referred
      to as 'Trichocomaceae gen. nov.' in those threat lists. 

PMID- 26203418
TI  - Identification of a new order of root-colonising fungi in the Entorrhizomycota:
      Talbotiomycetales ord. nov. on eudicotyledons.
AB  - The recently described fungal phylum Entorrhizomycota was established solely for
      the genus Entorrhiza, species of which cause root-galls in Cyperaceae and
      Juncaceae. Talbotiomyces calosporus (incertae sedis) shares morphological
      characteristics and an ecological niche with species of Entorrhiza. We
      investigated the higher classification of T. calosporus to determine whether it
      belongs in Entorrhizomycota. Ribosomal DNA sequences showed Talbotiomyces to be a
      close relative of Entorrhiza and both taxa form a highly supported monophyletic
      group. Based on molecular phylogenetic analyses and in congruence with existing
      morphological and ecological data, Entorrhiza and Talbotiomyces represent a deep
      dichotomy within the Entorrhizomycota. While species of Entorrhiza are
      characterised by dolipores and occur on monocotyledons, members of Talbotiomyces
      are characterised by simple pores and are associated with eudicotyledons. This
      expands the host range of the recently described Entorrhizomycota from Poales to
      other angiosperms. Higher taxa, namely Talbotiomycetales ord. nov. and
      Talbotiomycetaceae fam. nov., are proposed here to accommodate Talbotiomyces. 

PMID- 26203420
TI  - Recommendations of generic names in Diaporthales competing for protection or use.
AB  - In advancing to one name for fungi, this paper treats generic names competing for
      use in the order Diaporthales (Ascomycota, Sordariomycetes) and makes a
      recommendation for the use or protection of one generic name among synonymous
      names that may be either sexually or asexually typified. A table is presented
      that summarizes these recommendations. Among the genera most commonly encountered
      in this order, Cytospora is recommended over Valsa and Diaporthe over Phomopsis.
      New combinations are introduced for the oldest epithet of important species in
      the recommended genus. These include Amphiporthe tiliae, Coryneum lanciforme,
      Cytospora brevispora, C. ceratosperma, C. cinereostroma, C. eugeniae, C. fallax,
      C. myrtagena, Diaporthe amaranthophila, D. annonacearum, D. bougainvilleicola, D.
      caricae-papayae, D. cocoina, D. cucurbitae, D. juniperivora, D.
      leptostromiformis, D. pterophila, D. theae, D. vitimegaspora, Mastigosporella
      georgiana, Pilidiella angustispora, P. calamicola, P. pseudogranati, P.
      stromatica, and P. terminaliae. 

PMID- 26203421
TI  - Uromyces hawksworthii nom. nov. for Aecidium goyazense, on Phthirusa stelis
      (Loranthaceae) from the Brazilian Cerrado.
AB  - The sexual morph of Aecidium goyazense collected in the Brazilian Cerrado was
      morphologically characterized by light microscopy and SEM, and shown to be a
      species of Uromyces, for which the name Uromyces hawksworthii nom. nov. is
      introduced, and designated as its epitype. This is the second Uromyces species
      known to infect the tropical genus Phthirusa (Loranthaceae). DNA sequences were
      generated from the ITS and 28S rRNA (LSU) regions of DNA recovered from
      aeciospores as well as teliospores. This fungus is compared with other Uromyces
      species known from Loranthaceae. 

PMID- 26203423
TI  - Proposals to clarify and enhance the naming of fungi under the International Code
      of Nomenclature for algae, fungi, and plants.
AB  - Twenty-three proposals to modify the International Code of Nomenclature for
      algae, fungi, and plants adopted in 2011 with respect to the provisions for fungi
      are made, in accordance with the wishes of mycologists expressed at the 10(th)
      International Mycological Congress in Bangkok in 2014, and with the support of
      the International Commission on the Taxonomy of Fungi (ICTF), the votes of which
      are presented here. The proposals relate to: conditions for epitypification,
      registration of later typifications, protected lists of names, removal of
      exemptions for lichen-forming fungi, provision of a diagnosis when describing a
      new taxon, citation of sanctioned names, avoiding homonyms in other kingdoms,
      ending preference for sexually typified names, and treatment of conspecific names
      with the same epithet. These proposals are also being published in Taxon, will be
      considered by the Nomenclature Committee for Fungi and General Committee on
      Nomenclature, and voted on at the 19(th) International Botanical Congress in
      Shenzhen, China, in 2017. 

PMID- 26203422
TI  - The Genera of Fungi - fixing the application of the type species of generic names
      - G 2: Allantophomopsis, Latorua, Macrodiplodiopsis, Macrohilum, Milospium,
      Protostegia, Pyricularia, Robillarda, Rotula, Septoriella, Torula, and
      Wojnowicia.
AB  - The present paper represents the second contribution in the Genera of Fungi
      series, linking type species of fungal genera to their morphology and DNA
      sequence data, and where possible, ecology. This paper focuses on 12 genera of
      microfungi, 11 of which the type species are neo- or epitypified here:
      Allantophomopsis (A. cytisporea, Phacidiaceae, Phacidiales, Leotiomycetes),
      Latorua gen. nov. (Latorua caligans, Latoruaceae, Pleosporales, Dothideomycetes),
      Macrodiplodiopsis (M. desmazieri, Macrodiplodiopsidaceae, Pleosporales,
      Dothideomycetes), Macrohilum (M. eucalypti, Macrohilaceae, Diaporthales,
      Sordariomycetes), Milospium (M. graphideorum, incertae sedis, Pezizomycotina),
      Protostegia (P. eucleae, Mycosphaerellaceae, Capnodiales, Dothideomycetes),
      Pyricularia (P. grisea, Pyriculariaceae, Magnaporthales, Sordariomycetes),
      Robillarda (R. sessilis, Robillardaceae, Xylariales, Sordariomycetes), Rutola (R.
      graminis, incertae sedis, Pleosporales, Dothideomycetes), Septoriella (S.
      phragmitis, Phaeosphaeriaceae, Pleosporales, Dothideomycetes), Torula (T.
      herbarum, Torulaceae, Pleosporales, Dothideomycetes) and Wojnowicia (syn. of
      Septoriella, S. hirta, Phaeosphaeriaceae, Pleosporales, Dothideomycetes). Novel
      species include Latorua grootfonteinensis, Robillarda africana, R. roystoneae, R.
      terrae, Torula ficus, T. hollandica, and T. masonii spp. nov., and three new
      families: Macrodiplodiopsisceae, Macrohilaceae, and Robillardaceae. Authors
      interested in contributing accounts of individual genera to larger multi-authored
      papers to be published in IMA Fungus, should contact the associate editors listed
      for the major groups of fungi on the List of Protected Generic Names for Fungi
      (www.generaoffungi.org). 

PMID- 26203424
TI  - Homothallism: an umbrella term for describing diverse sexual behaviours.
AB  - Sexual reproduction is notoriously complex in fungi with species able to produce
      sexual progeny by utilizing a variety of different mechanisms. This is even more
      so for species employing multiple sexual strategies, which is a surprisingly
      common occurrence. While heterothallism is relatively well understood in terms of
      its physiological and molecular underpinnings, homothallism remains greatly
      understudied. This can be attributed to it involving numerous genetically
      distinct mechanisms that all result in self-fertility; including primary
      homothallism, pseudohomothallism, mating type switching, and unisexual
      reproduction. This review highlights the need to classify these homothallic
      mechanisms based on their molecular determinants and illustrates what is
      currently known about the multifaceted behaviours associated with homothallism. 

PMID- 26203425
TI  - Basidioascus undulatus: genome, origins, and sexuality.
AB  - Basidioascus undulatus is a soil basidiomycete belonging to the order
      Geminibasidiales. The taxonomic status of the order was unclear as originally it
      was only tentatively classified in the class Wallemiomycetes. The fungi in
      Geminibasidiales have an ambiguously defined sexual cycle. In this study, we
      sequenced the genome of B. undulatus to gain insights into its sexuality and
      evolutionary origins. The assembled genome draft was approximately 32 Mb in size,
      had a median nucleotide coverage of 24X, and contained 6123 predicted genes.
      Previous morphological descriptions of B. undulatus relied on interpretation of
      putative sexual structures. In this study, nuclear staining and confocal
      microscopy showed meiosis occurring in basidia and genome analysis confirmed the
      existence of genes involved in meiosis and mating. Using 35 protein-coding genes
      extracted from genomic information, phylogenomic and molecular dating analyses
      confirmed that B. undulatus indeed belongs to a lineage distantly related to
      Wallemia while retaining a basal position in Agaricomycotina. These results,
      combined with differences in septal pore morphology, led us to move the order
      Geminibasidiales out of the Wallemiomycetes and into the new class
      Geminibasidiomycetes cl. nov. Finally, the concept of Agaricomycotina is emended
      to include both Wallemiomycetes and Geminibasidiomycetes. 

PMID- 26203427
TI  - Ganoderma species, including new taxa associated with root rot of the iconic
      Jacaranda mimosifolia in Pretoria, South Africa.
AB  - Jacaranda mimosifolia trees have been progressively dying due to Ganoderma root
      and butt rot disease in Pretoria (the "City of Jacarandas") for many years.
      Ganoderma austroafricanum was described from these trees previously but this was
      based on a single collection. This study treats a substantially expanded
      collection of isolates of Ganoderma made from all dying trees where basidiomes
      were present in a Pretoria suburb. DNA sequences were obtained from the ITS and
      LSU region for the isolates and compared against sequences on GenBank.
      Phylogenetic analyses were used to compare sequences with those for other
      Ganoderma species. Based on sequence comparisons and morphological characters,
      two new Ganoderma species were discovered and these are described here as G.
      enigmaticum and G. destructans spp. nov. Interestingly, the previously described
      G. austroafricanum was not found, G. enigmaticum was found on only one Ceratonia
      siliqua tree and G. destructans was found on all other trees sampled. The latter
      species appears to be the primary cause of root rot of J. mimosifolia in the area
      sampled. 

PMID- 26203426
TI  - IMA Genome-F 4: Draft genome sequences of Chrysoporthe austroafricana, Diplodia
      scrobiculata, Fusarium nygamai, Leptographium lundbergii, Limonomyces culmigenus,
      Stagonosporopsis tanaceti, and Thielaviopsis punctulata.
AB  - The genomes of Chrysoporthe austroafricana, Diplodia scrobiculata, Fusarium
      nygami, Leptographium lundbergii, Limonomyces culmigenus, Stagonosporopsis
      tanaceti, and Thielaviopsis punctulata are presented in this genome announcement.
      These seven genomes are from endophytes, plant pathogens and economically
      important fungal species. The genome sizes range from 26.6 Mb in the case of
      Leptographium lundbergii to 44 Mb for Chrysoporthe austroafricana. The
      availability of these genome data will provide opportunities to resolve
      longstanding questions regarding the taxonomy of species in these genera, and may
      contribute to our understanding of the lifestyles through comparative studies
      with closely related organisms. 

PMID- 26203428
TI  - Provider beliefs associated with cervical cancer screening interval
      recommendations: A pilot study in Federally Qualified Health Centers.
AB  - BACKGROUND: Among providers who serve low-income and uninsured women, resistance
      to extending the cervical cancer screening interval following normal Pap and co
      test results has been documented. Our objective was to examine provider
      characteristics and beliefs associated with guideline-consistent screening
      interval recommendations. METHOD: We collected cross-sectional survey data
      between 2009 and 2010 from 82 primary care providers in six Federally Qualified
      Health Centers in Illinois, USA. The relationships between characteristics,
      beliefs, and screening interval recommendations (1 year vs. 3 years) were tested
      with Pearson chi-square, negative binomial and ordered logistic regression.
      RESULTS: Compared to providers who recommended annual intervals after a normal co
      test, providers who recommended a guideline-consistent (i.e., 3 years) screening
      interval were significantly more likely to report the goodness, ease, and benefit
      of their recommendation and perceived encouragement for a 3-year interval from
      professional organizations and journals (p < .05). Providers who recommended a 3
      year interval were also less likely to report that longer intervals increase
      patient risk for cervical cancer (p < .05). Interval recommendations were not
      associated with provider specialty, gender, or years in practice. CONCLUSION:
      Messages that promote the benefits of longer screening intervals after a normal
      co-test, the natural history of human papillomavirus and cervical cancer, and low
      risk of developing cancer with a longer interval may be useful to promote
      evidence-based screening in this population of Federally Qualified Health Center
      providers. Dissemination of targeted messages through professional journals and
      specialty organizations should be considered.

PMID- 26203429
TI  - Determine the relationship between perceived social support and depression level
      of patients with diabetic foot.
AB  - BACKGROUND: As a lifelong disease, diabetes impairs the quality of life by
      limiting the eating and drinking habits and by bringing out the risk of kidney,
      eye, cardiovascular and diabetic neurological diseases in the long run. Loss of
      health might result in mourning, grief, rebellion, denial, anxiety, rage and
      sometimes these feelings might overcome the patient's coping skills leading to
      depression [Clinical Psychiatry 11 (Suppl 3) 3-18, 2008]. How individuals
      suffering from depression perceive and interpret the incidents around them is
      also important [Rel. Scie. Acad. J. III, 2: 129-152, 2003]. Accordingly, the
      determination of the correlation of the depression with the perceived social
      support level by the patients with diabetic foot was programmed and performed in
      order to take essential precautions, to generate proper solutions and treatment
      process and to make supportive plans for patients with developing diabetic foot
      and depression. METHODS: The data was obtained from 128 patients who applied to
      hospital within the scope of research between July 1st 2011 and January 31st 2012
      that were diagnosed with diabetes and had diabetic foot. Pearson chi-square,
      Fisher Exact and Likelihood ratio, chi-square, Student t test and one way
      analysis of variance, Levene' s test, One way ANOVA, Welch and Games Howell tests
      were used in the analysis and evaluation. The data was collected by meeting face
      to face the individuals and by making use of the patient files and using the
      "Personal Information Form" which includes introductory information about
      individuals with diabetic foot, "Beck Depression Scale" which is applied to
      determine emotion status of individuals and "Multidimensional Scale of Perceived
      Social Support" which is applied to determine the level of social support
      individuals perceive. RESULTS: In the performed statistical evaluation, mean
      scores of Beck Depression scale and MSPSS family support, friend support, special
      person support sub-dimension and scale total scores were found to be in negative
      statistical correlation (p < 0.01). CONCLUSIONS: In the treatment and care of the
      patients with diabetic foot; anxiety and depression status of the patients, as
      well as physical status, should also be evaluated routinely. The individuals
      provided to take professional care.

PMID- 26203430
TI  - Prevalence and factors associated with metabolic syndrome among Tamils aged over
      18 years in Jaffna district, Sri Lanka.
AB  - BACKGROUND: The aim was to determine the prevalence and factors associated with
      Metabolic Syndrome (MS) among adults aged over 18 years in Jaffna district, Sri
      Lanka. METHODS: This study was carried out as a community based cross sectional
      descriptive study in Jaffna district, Sri Lanka. Multistage stratified cluster
      sampling technique was employed. Total sample size was 544. An interviewer
      administrated questionnaire was used to gather data. Waist circumference (WC) and
      blood pressure (BP) measurements were recorded in standard method. Overnight
      fasting blood samples were obtained from all subjects. Fasting plasma glucose
      (FPG), high density lipoprotein (HDL), and triacylglycerols were analyzed by the
      enzymatic colorimetric assay (Semi Automated analyser Teco Diagnostics TC 3300).
      Modified National Cholesterol Education Program's Adult Treatment Panel III (NCEP
      ATP III) criterion was used to define the MS. RESULTS: Sample response rate was
      95.3 %. Of them, 43.8 % (n = 224) was male. Prevalence of central obesity (WC for
      male >=102 cm, female >=88 cm) was 16.2 %. Prevalence of raised FPG (>=100
      mg/dL), hypertriacylglycerolaemia (>=150 mg/dl), low level of HDL cholesterol
      (<40 mg/dL in males, <50 mg/dL in females) and raised BP (systolic BP >=130 or
      diastolic BP >=85 mmHg) were 23.9, 25, 79.3 and 36.6 % respectively. Prevalence
      of MS was 24.1 % (n = 123, 95 % CI: 20.4-28) and it was 26.8 and 21.9 % among
      males and females respectively. Participants living in urban area had higher
      prevalence of MS when compared with participants living in rural area (P =
      0.015). Older age (P < 0.001) and smoking (P = 0.005) were risk factor for
      development of MS. Prevalence of MS among the participants with sedentary and
      active lifestyle was 29.9 and 23.7 % respectively. CONCLUSION: One out of four
      had MS. Old age, urban living and smoking carried higher risk for developing MS
      in Jaffna community.

PMID- 26203431
TI  - The association of vitamin D deficiency with psychiatric distress and violence
      behaviors in Iranian adolescents: the CASPIAN-III study.
AB  - BACKGROUND: Subtle effects of vitamin D deficiency on behavior have been
      suggested. We investigated the association of vitamin D status with mental health
      and violence behaviors in a sample of Iranian adolescents. METHODS: This
      nationwide study was conducted in 2009-2010 in 1095 Iranian school students with
      mean age 14.7 +/- 2.6 years. Items were adapted from the Global School-based
      Student Health Survey (GSHS). Psychiatric distress was considered as the self
      reported anger, anxiety, poor quality sleep, confusion, sadness/depression,
      worry, and violence-related behaviors (physical fight, having bully, or getting
      bullied). RESULTS: Forty percent had serum 25(OH)D values below 10 ng/mL (vitamin
      D deficient), and 39 % had levels 10-30 ng/mL (vitamin D insufficient). The
      prevalence of self-reported anger, anxiety, poor quality sleep,
      sadness/depression, and worry was significantly lower (P < 0.05) in vitamin D
      sufficient participants compared with their other counterparts. The odds of
      reporting anger, anxiety, poor quality sleep, and worry, increased approximately
      1.5 to 1.8 times in vitamin D insufficient compared with normal children and
      adolescents (P < 0.05). Risk estimates indicated that vitamin D insufficient and
      deficient subjects had higher odds of reporting worry compared to normal vitamin
      D group [OR = 2.417 (95 % CI: 1.483-3.940) for vitamin D insufficient students,
      and OR = 2.209 (95 % CI: 1.351-3.611) for vitamin D deficient students] (P-trend
      = 0.001). Violence behaviors did not show any association with vitamin D status
      (P > 0.05). CONCLUSION: Some psychiatric distress such as anger, anxiety, poor
      quality sleep, depression, and worry are associated with hypovitaminosis D in
      adolescents. The clinical significance of the current findings should be
      determined in future longitudinal studies.

PMID- 26203432
TI  - The Need for Advanced Training in Gastroenterology.

PMID- 26203433
TI  - A Bronchogenic Cyst Presenting as Dysphagia.

PMID- 26203434
TI  - Protein Shakes: An Unusual Cause of Gastric Phytobezoar.

PMID- 26203435
TI  - Traumatic Isolated Intramural Duodenal Hematoma Causing Intestinal Obstruction.

PMID- 26203436
TI  - Rectal Pain and the Colonic Crunch Sign.

PMID- 26203437
TI  - Intrasplenic Pancreatic Pseudocyst: A Rare Complication of Acute Pancreatitis.

PMID- 26203438
TI  - Intraductal Papillary Mucinous Neoplasms of Pancreas: The Good, the Bad, and the
      Ugly.

PMID- 26203439
TI  - Painless Jaundice Caused by Metastatic Renal Cell Carcinoma to the Distal Common
      Bile Duct.

PMID- 26203440
TI  - Calciphylaxis in a Patient With Alcoholic Cirrhosis.

PMID- 26203441
TI  - The Wrong Side: A Rare Case of Wandering Liver in a 78-Year-Old Man.

PMID- 26203442
TI  - Esophagogastric Fistula Caused by an Angelchik Antireflux Prosthesis.
AB  - The Angelchik prosthesis is an antireflux device that was popular in the 1980s
      for treatment of refractory gastroesophageal reflux disease (GERD). We present a
      patient who developed a gastroesophageal fistula 17 years after Angelchik
      prosthesis placement. The incidence of late complications continues to grow, and
      clinicians should consider device malfunction in patients with history of
      Angelchik placement presenting with abdominal symptoms. 

PMID- 26203443
TI  - Polyethylene Glycol (PEG)-Induced Anaphylactic Reaction During Bowel Preparation.
AB  - Barium enema is used to screen patients with gastrointestinal bleeding who do not
      want to undergo colonoscopy. Polyethylene glycol (PEG) is usually the bowel
      preparation of choice. Few allergic reactions from this product have been
      reported; these include urticaria, angioedema, and anaphylaxis. Reactions are
      thought to result from a small amount of PEG crossing the intestinal mucosa,
      which, in some patients, is sufficient to provoke an anaphylactic reaction. 

PMID- 26203444
TI  - Colonic Diverticulitis After Endoscopic Band Ligation Performed for Colonic
      Diverticular Hemorrhage.
AB  - A 72-year-old woman presented with massive hematochezia. Colonoscopy revealed
      active bleeding from a diverticulum in the ascending colon, diagnosed as colonic
      diverticular hemorrhage. Endoscopic band ligation (EBL) was performed for the
      hemostasis. The patient developed abdominal pain in the right lower quadrant 1
      day after EBL. Computed tomography (CT) demonstrated dirty fat around the
      ascending colon and thickened peritoneum without perforation or abscess
      formation, consistent with uncomplicated diverticulitis. The patient was
      discharged with intravenous antibiotic therapy 5 days after EBL. Attention should
      be given to the occurrence of colonic diverticulitis after EBL for colonic
      diverticular hemorrhage. 

PMID- 26203445
TI  - Perforation of a Long-standing Ileocolonic Anastomosis During Colonoscopy.
AB  - Colonoscopy is a valuable diagnostic and therapeutic procedure. Colonic
      perforation is a serious complication of colonoscopy that must be promptly
      recognized to limit morbidity and mortality. We present a 69-year-old woman who,
      during colonoscopy, had a perforation secondary to barotrauma of a long-standing
      ileocolonic anastomosis proximal to the point of colonoscopic intubation. To our
      knowledge, this is the first case report of a perforation of a well-established
      anastomosis proximal to the point of endoscope intubation during colonoscopy. 

PMID- 26203446
TI  - Rare Synchronous Gastrointestinal Plasmacytomas of Colon and Stomach.
AB  - Gastrointestinal (GI) plasmacytomas, though relatively uncommon, can occur with
      or without multiple myeloma. The small intestine is the most commonly involved GI
      site, followed by stomach, colon, and esophagus. Synchronous plasmacytomas
      involving 2 anatomically distinct regions of gastrointestinal tract have never
      been reported in the literature. We report a case of a multiple myeloma patient
      who had acute-onset hematochezia and was found to have synchronous plasmacytomas
      of the colon and stomach. 

PMID- 26203448
TI  - A Case of Clostridium septicum Aortitis With Concomitant Adenocarcinoma of the
      Cecum.
AB  - Clostridium septicum aortitis is a rare infection that is strongly associated
      with underlying adenocarcinoma of the colon. We report a case of a 73-year-old
      woman with peripheral vascular disease who presented after 4 weeks of severe
      abdominal pain. Abdominal computed tomography showed thickening of the cecal wall
      and gas in the aortic wall. Colonoscopy revealed a large ulcerated moderately
      differentiated adenocarcinoma in the cecum. Blood cultures grew Clostridium
      septicum. The patient was offered surgical intervention but refused; she was
      treated with antibiotics and discharged home where she died 1 week later. 

PMID- 26203447
TI  - Magnesium Toxicity-Induced Ileus in a Postpartum Patient Treated for Preeclampsia
      With Magnesium Sulphate.
AB  - Hypermagnesemia is a rare and under-recognized cause of paralytic ileus. We
      report a case of a 21-year-old primigravida who was managed aggressively for
      preeclampsia and presented with postpartum paralytic ileus. Detailed history was
      employed to consider hypermagnesemia-induced ileus as the working diagnosis, and
      the patient improved with correction of the electrolyte imbalance.
      Hypermagnesemia-induced lethargy, decreased reflexes, muscle weakness, flaccid
      paralysis, respiratory muscle paralysis, and cardiac arrest are well-described;
      however, intestinal smooth muscle dysfunction leading to paralytic ileus has
      never been reported in the setting of magnesium use for peripartum preeclampsia
      management. 

PMID- 26203449
TI  - Early Diagnosis of a Small Adenocarcinoma in a Rectovaginal Fistula Related to
      Crohn's Disease.
AB  - While adenocarcinomas have occasionally been reported in perianal fistulae,
      malignant changes occurring in rectovaginal fistulae are rare, with only a
      handful of reported cases. We report a 73-year-old woman with Crohn's disease who
      was diagnosed at an early stage with adenocarcinoma in a rectovaginal fistula.
      This rare disease poses many diagnostic challenges. 

PMID- 26203450
TI  - Successful Treatment of Ulcerative Colitis With Vedolizumab in a Patient With an
      Infliximab-Associated Psoriasiform Rash.
AB  - Psoriatic skin lesions associated with anti-tumor necrosis factor (TNF) agents
      are well-described in the medical literature. However, the etiology and optimal
      management of this condition remain unclear. Vedolizumab is a novel, gut
      specific, anti-integrin agent used for the treatment of inflammatory bowel
      disease (IBD). We report a case of infliximab-associated psoriasiform lesions in
      an ulcerative colitis patient. Transition to vedolizumab resulted in resolution
      of the cutaneous lesions without recurrence and remission of his ulcerative
      colitis. 

PMID- 26203451
TI  - Eosinophilic Pancreatitis Diagnosed With Endoscopic Ultrasound.
AB  - Eosinophilic pancreatitis (EP) is a rare clinical entity, and few cases have been
      reported. It usually presents on imaging as a pancreatic mass leading to common
      bile duct obstruction and jaundice. Since it can mimic a malignancy, eosinophilic
      pancreatitis is often diagnosed after "false positive" pancreatic resections. To
      our knowledge, we report the only known case of EP in which the diagnosis was
      made by fine needle aspiration and core biopsy of the pancreas during EUS,
      sparing the patient a surgical resection. After a steroid course, there was
      improvement of clinical symptoms. 

PMID- 26203452
TI  - Pericardiobiliary Fistulation: A Rare Complication of Therapeutic ERCP in a
      Patient With IgG4-Related Sclerosing Cholangitis.
AB  - A 70-year-old man presented with acute coronary syndrome 3 weeks after plastic
      stent insertion for hilar biliary stricturing secondary to IgG4-related
      sclerosing cholangitis (IgG4-SC). Imaging demonstrated haemopericardium due to
      proximal migration of the plastic biliary stent through the liver capsule and
      diaphragm into the pericardial sac. The stent was endoscopically removed and a
      pericardiocentesis was performed. The patient's clinical condition rapidly
      improved. We illustrate an unusual but potentially serious complication that may
      arise from migration of a biliary stent and discuss a management strategy. 

PMID- 26203453
TI  - Acalculous Cholecystitis Due to Histoplasma capsulatum in a Patient With HIV
      Infection.
AB  - Although acalculous cholecystitis typically occurs in critically ill individuals,
      it has been described in patients with HIV infection. Recognition of AIDS-related
      acalculous cholecystitis is important for gastroenterologists to provide optimal
      therapy, since many different opportunistic pathogens may be involved.
      Histoplasma capsulatum causes a wide spectrum of infectious sequelae, including
      disseminated histoplasmosis in patients with HIV infection, but biliary tract
      involvement has been described infrequently. We present a case of acalculous
      cholecystitis caused by H. capsulatum in a patient with HIV infection. 

PMID- 26203454
TI  - Autoimmune Hepatitis Triggered by Treatment With Pegylated Interferon alpha-2a
      and Ribavirin for Chronic Hepatitis C.
AB  - Hepatitis flare is rarely observed during treatment with pegylated interferon
      alpha for hepatitis C virus (HCV) infection. A 49-year-old man receiving
      pegylated interferon alpha-2a for HCV infection had icterus and hyperbiliru
      binemia in the 14th week of therapy, with HCV RNA undetectable after the 12th
      dose. Liver biopsy was suggestive of chronic hepatitis with cirrhosis without
      interface pattern. Pegylated interferon was discontinued; a few weeks later, his
      aminotransferases and immunoglobulin levels increased significantly. Antibody to
      cytosolic liver antigen-1 was positive, and liver biopsy revealed
      lymphoplasmacytic infiltrate with intense interface hepatitis, consistent with
      autoimmune hepatitis. 

PMID- 26203455
TI  - Hemolysis in Acute Alcoholic Hepatitis: Zieve's Syndrome.
AB  - A 45-year-old man presented with acute alcoholic hepatitis, jaundice, and anemia
      on admission. There was no history of bleeding or any evidence of
      gastrointestinal blood loss. Lab studies revealed hemolysis as the cause of
      anemia. The patient was diagnosed with Zieve's syndrome and managed with
      supportive measures. He recovered well and was discharged to a detoxification
      unit in a stable condition. Zieve's syndrome has been described in literature,
      mostly in non-English language case studies, but is largely under-recognized and
      under-reported. Diagnosis should be made quickly to avoid unnecessary invasive
      diagnostic interventions. 

PMID- 26203456
TI  - A Large Refilling Cystic Lesion In A Gastric Bypass Patient.
AB  - We describe a patient with a history of gastric bypass and chronic alcoholism
      suffering from a rare Peterson's hernia resulting from her surgery. There are a
      few case reports in which afferent loop obstruction was misdiagnosed as
      pancreatic pseudocyst after Billroth II gastrectomy. Ours is the first in which
      Peterson's hernia was initially misdiagnosed as a pancreatic pseudocyst in a
      gastric bypass patient. 

PMID- 26203457
TI  - Solitary Septated Simple Liver Cyst in a Newborn Infant.
AB  - Simple liver cysts (SLC) are generally rare and are typically symptomatic when
      detected in infancy. We present a case of a newborn infant in whom fetal
      ultrasound and MRI revealed a cystic structure. Postnatal imaging revealed a
      septated, single cystic structure causing mass effect on the common bile duct and
      partially obstructing the inferior vena cava. Treatment of a solitary septated
      SLC was successful by laparoscopic total excision. The infant had an
      uncomplicated postsurgical course and has done well. 

PMID- 26203458
TI  - Mesenchymal Hamartoma of the Liver in an Infant With Beckwith-Wiedemann Syndrome:
      A Rare Condition Mimicking Hepatoblastoma.
AB  - Patients with Beckwith-Wiedemann syndrome (BWS) are known to be at an increased
      risk for childhood malignancies, particularly Wilms tumor and hepatoblastoma. We
      report a case of genetically confirmed BWS in a 5-month-old girl who presented
      with a 9.5-cm abdominal mass associated with elevated alpha-fetoprotein levels.
      The clinical impression was strongly suggestive of hepatoblastoma. Histologic
      examination of the surgically excised mass revealed mesenchymal hamartoma of the
      liver (MHL), a benign hepatic neoplasm. 

PMID- 26203459
TI  - The Role of Gratitude in Spiritual Well-being in Asymptomatic Heart Failure
      Patients.
AB  - Spirituality and gratitude are associated with wellbeing. Few if any studies have
      examined the role of gratitude in heart failure (HF) patients or whether it is a
      mechanism through which spirituality may exert its beneficial effects on physical
      and mental health in this clinical population. This study examined associations
      bet ween gratitude, spiritual wellbeing, sleep, mood, fatigue, cardiac-specific
      self-efficacy, and inflammation in 186 men and women with Stage B asymptomatic HF
      (age 66.5 years +/-10). In correlational analysis, gratitude was associated with
      better sleep (r=-.25, p<0.01), less depressed mood (r=-.41, p<0.01), less fatigue
      (r=-.46, p<0.01), and better self-efficacy to maintain cardiac function (r=.42,
      p<0.01). Patients expressing more gratitude also had lower levels of inflammatory
      biomarkers (r=-.17, p<0.05). We further explored relationships among these
      variables by examining a putative pathway to determine whether spirituality
      exerts its beneficial effects through gratitude. We found that gratitude fully
      mediated the relationship between spiritual wellbeing and sleep quality (z=-2.35,
      SE=.03, p=.02) and also the relationship between spiritual wellbeing and
      depressed mood (z=-4.00, SE=.075, p<.001). Gratitude also partially mediated the
      relationships between spiritual wellbeing and fatigue (z=-3.85, SE=.18, p<.001),
      and between spiritual wellbeing and self-efficacy (z=2.91, SE=.04, p=.003). In
      sum, we report that gratitude and spiritual wellbeing are related to better mood
      and sleep, less fatigue, and more self-efficacy, and that gratitude fully or
      partially mediates the beneficial effects of spiritual wellbeing on these
      endpoints. Efforts to increase gratitude may be a treatment for improving
      wellbeing in HF patients' lives and be of potential clinical value.

PMID- 26203460
TI  - Dissecting the Genetic Architecture of Behavior in Drosophila melanogaster.
AB  - Variation in behaviors in natural populations arises from complex networks of
      multiple segregating polymorphic alleles whose expression can be modulated by the
      environment. Since behaviors reflect dynamic interactions between organisms and
      their environments, they are central targets for adaptive evolution. Drosophila
      melanogaster presents a powerful system for dissecting the genetic basis of
      behavioral phenotypes, since both the genetic background and environmental
      conditions can be controlled and behaviors accurately quantified. Single gene
      mutational analyses can identify the roles of individual genes within cellular
      pathways, whereas systems genetic approaches that exploit natural variation can
      construct genetic networks that underlie phenotypic variation. Combining these
      approaches with emerging technologies, such as genome editing, is likely to yield
      a comprehensive understanding of the neurogenetic underpinnings that orchestrate
      the manifestation of behaviors.

PMID- 26203461
TI  - Web-enabled Conversational Interactions as a Means to Improve Cognitive
      Functions: Results of a 6-Week Randomized Controlled Trial.
AB  - INTRODUCTION: Increasing social interaction could be a promising intervention for
      improving cognitive function. We examined the feasibility of a randomized
      controlled trial to assess whether conversation-based cognitive stimulation,
      through personal computers, webcams, and a user-friendly interactive Internet
      interface had high adherence and a positive effect on cognitive functions among
      older adults without dementia. METHODS: Daily 30 minute face-to-face
      communications were conducted over a 6-week trial period in the intervention
      group. The control group had only a weekly telephone interview. Cognitive status
      of normal and MCI subjects was operationally defined as Global Clinical Dementia
      Rating (CDR) = 0 and 0.5, respectively. Age, sex, education, Mini-Mental State
      Exam and CDR score were balancing factors in randomization. Subjects were
      recruited using mass-mailing invitations. Pre-post differences in cognitive test
      scores and loneliness scores were compared between control and intervention
      groups using linear regression models. RESULTS: Eighty-three subjects
      participated (intervention: n=41, control: n=42). Their mean (std) age was 80.5
      (6.8) years. Adherence to the protocol was high; there was no dropout and mean %
      of days completed out of the targeted trial days among the intervention group was
      89% (range: 77%-100%). Among the cognitively intact participants, the
      intervention group improved more than the control group on a semantic fluency
      test (p=0.003) at the post-trial assessment and a phonemic fluency test (p=0.004)
      at the 18th week assessments. Among those with MCI, a trend (p=0.04) of improved
      psychomotor speed was observed in the intervention group. DISCUSSION: Daily
      conversations via user-friendly Internet communication programs demonstrated high
      adherence. Among cognitively intact, the intervention group showed greater
      improvement in tests of language-based executive functions. Increasing daily
      social contacts through communication technologies could offer cost-effective
      home-based preventions. Further studies with a longer duration of follow-up are
      required to examine whether the intervention slows cognitive declines and delays
      the onset of dementia.

PMID- 26203463
TI  - Enhanced GABAergic Inputs Contribute to Functional Alterations of Cholinergic
      Interneurons in the R6/2 Mouse Model of Huntington's Disease.
AB  - In Huntington's disease (HD), a hereditary neurodegenerative disorder, striatal
      medium-sized spiny neurons undergo degenerative changes. In contrast, large
      cholinergic interneurons (LCIs) are relatively spared. However, their ability to
      release acetylcholine (ACh) is impaired. The present experiments examined
      morphological and electrophysiological properties of LCIs in the R6/2 mouse model
      of HD. R6/2 mice show a severe, rapidly progressing phenotype. Immunocytochemical
      analysis of choline acetyltransferase-positive striatal neurons showed that,
      although the total number of cells was not changed, somatic areas were
      significantly smaller in symptomatic R6/2 mice compared to wildtype (WT)
      littermates, For electrophysiology, brain slices were obtained from
      presymptomatic (3-4 weeks) and symptomatic (>8 weeks) R6/2 mice and their WT
      littermates. Striatal LCIs were identified by somatic size and spontaneous action
      potential firing in the cell-attached mode. Passive and active membrane
      properties of LCIs were similar in presymptomatic R6/2 and WT mice. In contrast,
      LCIs from symptomatic R6/2 animals displayed smaller membrane capacitance and
      higher input resistance, consistent with reduced somatic size. In addition, more
      LCIs from symptomatic mice displayed irregular firing patterns and bursts of
      action potentials. They also displayed a higher frequency of spontaneous
      GABAergic inhibitory postsynaptic currents (IPSCs) and larger amplitude of
      electrically evoked IPSCs. Selective optogenetic stimulation of somatostatin- but
      not parvalbumin-containing interneurons also evoked larger amplitude IPSCs in
      LCIs from R6/2 mice. In contrast, glutamatergic spontaneous or evoked
      postsynaptic currents were not affected. Morphological and electrophysiological
      alterations, in conjunction with the presence of mutant huntingtin in LCIs, could
      explain impaired ACh release in HD mouse models.

PMID- 26203466
TI  - Interview with Ben L. Feringa.

PMID- 26203462
TI  - Chromosomal Rearrangements in Cancer: Detection and potential causal mechanisms.
AB  - Many cancers exhibit chromosomal rearrangements. These rearrangements can be
      simple with a single balanced fusion preserving the proper complement of genetic
      information or they can be complex with one or more fusions that distort this
      balance. A range of technological advances has improved our ability to detect and
      understand these rearrangements leading to speculation of causal mechanisms
      including defective DNA double strand break (DSB) repair and faulty DNA
      replication. A better understanding of these potential cancer-causing mechanisms
      will lead to novel therapeutic regimes to fight cancer. This review describes the
      technological advances used to detect simple and complex chromosomal
      rearrangements, cancers that exhibit these rearrangements, potential mechanisms
      that rearrange chromosomes and intervention strategies designed to specifically
      attack fusion gene products and causal DNA repair/synthesis pathways.

PMID- 26203464
TI  - A Novel Method to Assess Bone Marrow Purity is Useful in Determining Blast
      Percentage by Flow Cytometry in Acute Myeloid Leukemia and Myelodysplasia.
AB  - Blast quantification by Flow Cytometry (FCM) may become essential in situations
      where morphologic evaluation is difficult or unavailable. As hemodilution
      invariably occurs, a means of determining Bone Marrow Purity (BMP) and
      normalizing FCM blast counts is essential, especially when blast percentages are
      diagnostically critical as in Acute Myeloid Leukemia (AML) and Myelodysplasia
      (MDS). By evaluating different leukocyte populations in eight initial patients, a
      formula to predict BMP was developed and compared to the actual BMP determined by
      manual counts. Performance of the formula was then validated in 86 AML/MDS
      patients by comparing normalized FCM blast counts to those determined by the
      reference manual method. A BMP formula was empirically developed, primarily based
      on changes in lymphocytes which reliably correlated with the actual BMP (R2 =
      0.8955). Components of the formula were derived entirely from automated
      lymphocyte and total leukocyte counts from the peripheral blood and FCM analyses.
      BMP formula was then validated in 86 AML/MDS patients. When used to normalize
      blast counts, the formula showed accurate correction when BMP fell between 40%
      90%. In this group, correlation of normalized FCM and manual blast counts was
      acceptable (R2 = 0.8335), being greatest at lower blast percentages.
      Normalization of the FCM blast count appropriately reclassified disease in 26.8%
      of cases. We identified a practical means of estimating hemodilution and allowing
      FCM blast normalization in the evaluation of AML and MDS. BMP assessment by this
      simple method improves the quality of the FCM data and facilitates accurate
      diagnosis and patient management.

PMID- 26203465
TI  - Spatial Big Data Analytics of Influenza Epidemic in Vellore, India.
AB  - The study objective is to develop a big spatial data model to predict the
      epidemiological impact of influenza in Vellore, India. Large repositories of
      geospatial and health data provide vital statistics on surveillance and
      epidemiological metrics, and valuable insight into the spatiotemporal
      determinants of disease and health. The integration of these big data sources and
      analytics to assess risk factors and geospatial vulnerability can assist to
      develop effective prevention and control strategies for influenza epidemics and
      optimize allocation of limited public health resources. We used the spatial
      epidemiology data of the HIN1 epidemic collected at the National Informatics
      Center during 2009-2010 in Vellore. We developed an ecological niche model based
      on geographically weighted regression for predicting influenza epidemics in
      Vellore, India during 2013-2014. Data on rainfall, temperature, wind speed,
      humidity and population are included in the geographically weighted regression
      analysis. We inferred positive correlations for H1N1 influenza prevalence with
      rainfall and wind speed, and negative correlations for H1N1 influenza prevalence
      with temperature and humidity. We evaluated the results of the geographically
      weighted regression model in predicting the spatial distribution of the influenza
      epidemic during 2013-2014.

PMID- 26203467
TI  - Electrochemical analysis of a novel ferrocene derivative as a potential antitumor
      drug.
AB  - Ferrocenes represent an interesting group of drugs with potential antitumor
      properties. Moreover, their electronic properties make them suitable for
      electrochemical studies. We determined an uptake of a novel ferrocene derivative
      in low MUM concentrations by selected cancer cell lines and showed its
      localization predominantly in cytoplasm, using glassy carbon electrodes. 

PMID- 26203468
TI  - Paper cone spray ionization mass spectrometry (PCSI MS) for simple and rapid
      analysis of raw solid samples.
AB  - We developed a modified paper spray ionization (PSI) platform, named as paper
      cone spray ionization (PCSI), for direct mass spectrometric analysis of raw solid
      samples. The major modification from conventional PSI was the geometry of the
      paper base: PCSI uses a triangular-pyramidal-shaped paper tip instead of a planar
      triangular-shaped one. This three-dimensional paper cone serves as a sample
      container, an in situ solid-liquid extraction chamber, an analyte transport
      channel, as well as an electrospray tip. Unlike conventional PSI mass
      spectrometry (MS), a weighing paper with relatively low permeability was found to
      be more suitable for PCSI MS than other papers. PCSI MS rapidly generated major
      chemical fingerprints from various solid materials including powdered tablets as
      well as raw and processed food materials without any sample pre-treatment. 

PMID- 26203469
TI  - Trans-Atlantic Debate: Whether Carotid Endarterectomy is Safer than  Stenting in
      the Hyperacute Period After Onset of Symptoms.

PMID- 26203470
TI  - Preface.

PMID- 26203471
TI  - Contact dermatitis masquerading as folliculitis decalvans: methylisothiazolinone
      strikes again!

PMID- 26203473
TI  - Retraction notice to "Monolayers of pigment-protein complexes on a bare gold
      electrode:Orientation controlled deposition and comparison of electron
      transferrate for two configurations" [Biosens. Bioelectron. 69 (2015)40-45].

PMID- 26203472
TI  - Managing anticoagulation in  patients receiving implantable  cardiac devices.
AB  - A substantial proportion of patients who undergo cardiac rhythm device
      implantation receive anticoagulation to prevent thromboembolism. Many patients
      have coexisting cardiovascular diseases treated with antiplatelet therapy.
      Anticoagulation may increase the risk of hemorrhagic complication, while
      withdrawal of anticoagulation may increase thromboembolic risk. In this article,
      we review and describe the available evidence, in order to inform best practice .

PMID- 26203474
TI  - Sheila Kitzinger MBE: 29th March 1929-11th April 2015. Reflections on her life
      and the legacy of her work.

PMID- 26203475
TI  - Change in primary midwife-led care in the Netherlands in 2000-2008: A descriptive
      study of caesarean sections and other interventions among 807,437 low-risk
      births.
AB  - OBJECTIVE: to study whether an increase in intrapartum referrals in primary
      midwife-led care births in the Netherlands is accompanied by an increase in
      caesarean sections. DESIGN: nationwide descriptive study. SETTING: The
      Netherlands Perinatal Registry. PARTICIPANTS: 807,437 births of nine year cohorts
      of women with low risk pregnancies in primary midwife-led care at the onset of
      labour between 2000 and 2008. MEASUREMENTS: primary outcome is the caesarean
      section rate. Vaginal instrumental childbirth, augmentation with oxytocin, and
      pharmacological pain relief are secondary outcomes. Trends in outcomes are
      described. We used logistic regression to explore whether changes in the planned
      place of birth and other maternal characteristics were associated with the
      caesarean section rate. FINDINGS: the caesarean section rate increased from 6.2
      to 8.3 per cent for nulliparous and from 0.8 to 1.1 per cent for multiparous
      women. After controlling for maternal characteristics the year by year increase
      in the caesarean section rate was still significant for nulliparous women (adj OR
      1.03; 95% CI 1.02-1.03). The vaginal instrumental birth declined from 18.2 to
      17.4 per cent for nulliparous women (multiparous women: 1.7-1.5 per cent).
      Augmentation of labour and/or pharmacological pain relief increased from 23.1 to
      38.1 per cent for nulliparous women and from 5.4 to 9.6 per cent for multiparous
      women. CONCLUSION: the rise in augmentation of labour, pharmacological pain
      relief and electronic fetal monitoring in the period 2000-2008 among women in
      primary midwife-led care was accompanied by an increase in caesarean section rate
      for nulliparous women. The vaginal instrumental deliveries declined for both
      nulliparous and multiparous women. IMPLICATIONS FOR PRACTICE: primary care
      midwives should evaluate whether they can strengthen the opportunities for
      nulliparous women to achieve a physiological birth, without augmentation or
      pharmacological pain relief. If such interventions are considered necessary to
      achieve a spontaneous vaginal birth, the current disadvantage of discontinuity of
      care should be reduced. In a more integrated care system, women could receive
      continuous care and support from their own primary care midwife, as long as only
      supportive interventions are needed.

PMID- 26203477
TI  - 2014 TOXCON. Connecting for safer Europe.

PMID- 26203476
TI  - Posttraumatic Stress Disorder: The Misappropriation of Military Suicide Causation
      and Medication Treatment of Posttraumatic Stress Disorder. Reply.

PMID- 26203494
TI  - Genetic Polymorphism of DNA Methyltransferase 3A rs1550117 A>G and Risk of
      Cancer: A Meta-analysis.
AB  - Numerous studies have investigated the association between DNMT3A rs1550117 A>G
      polymorphism and cancer risk, but the results are inconsistent. To obtain a more
      precise evaluation of the relationship, we performed a meta-analysis of 10 case
      control studies involving a total of 2184 cancer cases and 3420 controls. Our
      findings demonstrated a significant association between DNMT3A rs1550117 A>G
      polymorphism and increased risk of cancer in three genetic models: AA vs. AG + GG
      (OR, 1.79; 95% CI, 1.12-2.88; p = 0.015), AA vs. GG (OR, 1.81; 95% CI, 1.11-2.95;
      p = 0.018) and AA vs. AG (OR 1.77; 95% CI 1.13-2.79; p = 0.013). In a stratified
      analysis by cancer type, significant association between DNMT3A rs1550117 A>G
      polymorphism and increased risk of colorectal cancer was identified in four
      genetic models: AA vs. AG + GG (OR, 3.07; 95% CI, 1.56-6.06; p = 0.001), AA vs.
      GG (OR, 3.16; 95% CI, 1.58-6.29; p = 0.001), AA vs. AG (OR, 2.87; 95% CI, 1.41
      5.84; p = 0.004), A vs. G (OR, 1.43; 95% CI, 1.11-1.83; p = 0.005). Furthermore,
      a stratified analysis by ethnicity, significant increased risk of cancer was
      found among Asians in three genetic models: AA vs. AG + GG (OR, 1.77; 95% CI,
      1.09-2.88; p = 0.022), AA vs. GG (OR, 1.78; 95% CI, 1.08-2.96; p = 0.025), AA vs.
      AG (OR, 1.75; 95% CI, 1.10-2.79; p = 0.019). No significant publication bias was
      revealed for the meta-analysis. Sensitivity analysis suggested the reliability of
      our findings. In conclusion, this meta-analysis suggests that DNMT3A rs1550117
      A>G polymorphism may be associated with cancer susceptibility. 

PMID- 26203496
TI  - Electronic Spectroscopy of Resonantly Stabilized Aromatic Radicals: 1-Indanyl and
      Methyl Substituted Analogues.
AB  - The gas-phase electronic spectra of two resonantly stabilized radicals, 1-indanyl
      (C9H9) and 1-methyl-1-indanyl (C10H11), have been recorded in the visible region
      using a resonant two-color two-photon ionization (R2C2PI) scheme. The D1(A") <-
      D0(A") origin bands of 1-indanyl and 1-methyl-1-indanyl radicals are observed at
      21157 and 20565 cm(-1), respectively. The excitation of a' vibrations in the D1
      state is observed up to ~1500 cm(-1) above the origin band in both cases. The
      experimental assignments are in agreement with DFT and TD-DFT calculations. The
      R2C2PI spectrum recorded at m/z = 131 amu (C10H11) features three additional
      electronic transitions at 21433, 21369, and 17989 cm(-1), which are assigned to
      the origin bands of 7-methyl-1-indanyl, 2,3,4-trihydronaphthyl, and methyl-4
      ethenylbenzyl radicals, respectively.

PMID- 26203495
TI  - Proinflammatory Signature of the Dysfunctional Endothelium in Pulmonary
      Hypertension. Role of the Macrophage Migration Inhibitory Factor/CD74 Complex.
AB  - RATIONALE: Inflammation and endothelial dysfunction are considered two primary
      instigators of pulmonary arterial hypertension (PAH). CD74 is a receptor for the
      proinflammatory cytokine macrophage migration inhibitory factor (MIF). This
      ligand/receptor complex initiates survival pathways and cell proliferation, and
      it triggers the synthesis and secretion of major proinflammatory factors and cell
      adhesion molecules. OBJECTIVES: We hypothesized that the MIF/CD74 signaling
      pathway is overexpressed in idiopathic PAH (iPAH) and contributes to a
      proinflammatory endothelial cell (EC) phenotype. METHODS: Primary early passage
      cultures of human ECs isolated from lung tissues obtained from patients with iPAH
      and controls were examined for their ability to secrete proinflammatory mediators
      and bind inflammatory cells with or without modulation of the functional
      activities of the MIF/CD74 complex. In addition, we tested the efficacies of
      curative treatments with either the MIF antagonist ISO-1 or anti-CD74
      neutralizing antibodies on the aberrant proinflammatory EC phenotype in vitro and
      in vivo and on the progression of monocrotaline-induced pulmonary hypertension.
      MEASUREMENTS AND MAIN RESULTS: In human lung tissues, intercellular adhesion
      molecule-1, vascular cell adhesion molecule-1, and E-selectin expressions are
      markedly up-regulated in the endothelium of distal iPAH pulmonary arteries.
      Circulating MIF levels are increased in the serum of patients with PAH compared
      with control subjects, and T-cell lymphocytes represent a source of this
      overabundance. In addition, CD74 is highly expressed in the endothelium of
      muscularized pulmonary arterioles and in cultured pulmonary ECs from iPAH,
      contributing to an exaggerated recruitment of peripheral blood mononuclear cells
      to pulmonary iPAH ECs. Finally, we found that curative treatments with the MIF
      antagonist ISO-1 or anti-CD74 neutralizing antibodies partially reversed
      development of pulmonary hypertension in rats and substantially reduced
      inflammatory cell infiltration. CONCLUSIONS: We report here that CD74 and MIF are
      markedly increased and activated in patients with iPAH, contributing to the
      abnormal proinflammatory phenotype of pulmonary ECs in iPAH.

PMID- 26203497
TI  - Synthetic Quorum Sensing and Cell-Cell Communication in Gram-Positive Bacillus
      megaterium.
AB  - The components of natural quorum-sensing (QS) systems can be used to engineer
      synthetic communication systems that regulate gene expression in response to
      chemical signals. We have used the machinery from the peptide-based agr QS system
      from Staphylococcus aureus to engineer a synthetic QS system in Bacillus
      megaterium to enable autoinduction of a target gene at high cell densities.
      Growth and gene expression from these synthetic QS cells were characterized in
      both complex and minimal media. We also split the signal production and sensing
      components between two strains of B. megaterium to produce sender and receiver
      cells and characterized the resulting communication in liquid media and on
      semisolid agar. The system described in this work represents the first synthetic
      QS and cell-cell communication system that has been engineered to function in a
      Gram-positive host, and it has the potential to enable the generation of dynamic
      gene regulatory networks in B. megaterium and other Gram-positive organisms.

PMID- 26203498
TI  - Low Dose Naltrexone for Treatment of Multiple Sclerosis: A Retrospective Chart
      Review of Safety and Tolerability.

PMID- 26203499
TI  - Elucidating Protactinium Hydrolysis: The Relative Stabilities of PaO2(H2O)(+) and
      PaO(OH)2(+).
AB  - It is demonstrated that the gas-phase oxo-exchange of PaO2(+) with water is
      substantially faster than that of UO2(+), indicating that the Pa-O bonds are more
      susceptible to activation and formation of the bis-hydroxide intermediate,
      PaO(OH)2(+). To elucidate the nature of the water adduct of PaO2(+), hydration of
      PaO2(+) and UO2(+), as well as collision induced dissociation (CID) and ligand
      exchange of the water adducts of PaO2(+) and UO2(+), was studied. The results
      indicate that, in contrast to UO2(H2O)(+), the protactinium oxo bis-hydroxide
      isomer, PaO(OH)2(+), is produced as a gas-phase species close in energy to the
      hydrate isomer, PaO2(H2O)(+). CID behavior similar to that of Th(OH)3(+) supports
      the assignment as PaO(OH)2(+). The gas-phase results are consistent with the
      spontaneous hydrolysis of PaO2(+) in aqueous solution, this in contrast to later
      AnO2(+) (An = U, Np, Pu), which forms stable hydrates in both solution and gas
      phase. In view of the known propensity for Th(IV) to hydrolyze, and previous gas
      phase studies of other AnO2(+), it is concluded that the stabilities of oxo
      hydroxides relative to oxide hydrates decreases in the order: Th(IV) > Pa(V) >
      U(V) > Np(V) > Pu(V). This trend suggests increasing covalency and decreasing
      ionicity of An-O bonds upon proceeding across the actinide series. 

PMID- 26203500
TI  - So, frontline nurses, how much do you earn?

PMID- 26203501
TI  - Mental Health First Aid: triage for the mind.

PMID- 26203502
TI  - Empowering patients to self-manage in the context of incontinence.
AB  - Chronic diseases cause complex challenges and difficulties for patients, families
      and health professionals. With the increasing prevalence of chronic diseases,
      long-term treatment interventions may be required. Health professionals must
      empower patients to adhere to therapies and develop self-management strategies.
      The aetiology of bladder and bowel dysfunctions is multi-dimensional with some
      individuals who present with chronic disease being predisposed to urinary or
      faecal incontinence. This article will discuss the concepts of compliance,
      adherence and concordance approaches in the management of bladder and bowel
      dysfunction, focusing on the concept of self-management approaches to enhance
      patients' adherence to treatment regimens and maximise therapeutic outcomes. 

PMID- 26203503
TI  - Intermittent catheterisation for postoperative urinary retention.

PMID- 26203504
TI  - Nurses in independent care homes: issues, challenges and potential.
AB  - Many registered nurses in the UK work in the social care sector in independent
      care homes and nursing homes. This article explores the challenges related to
      providing nursing care for adults in care homes, issues arising for nurses and
      nursing in the social care sector, and providing a career pathway for nurses in
      the social care sector. Steps need to be taken to ensure that cooperation,
      collaboration and leadership in nursing in the social care sector is recognised
      and that appropriate representation of nurses in social care takes place at
      national level. 

PMID- 26203505
TI  - Management of pain following craniotomy.
AB  - Pain following craniotomy is common, however, achieving effective analgesia can
      be difficult. The assessment of pain postoperatively can be a challenge in
      patients who are obtunded (not fully alert) and the severity of pain has
      historically been underestimated. There are also concerns about side-effects from
      drugs, particularly with opioids, which may lead to reluctance to administer
      effective doses. Paracetamol is generally safe and, if given intravenously,
      provides rapid analgesia, although there are risks associated with overdose and
      care must be taken to ensure that the safe daily limit is not exceeded. Opioids
      are effective but side effects of pupillary constriction and respiratory
      depression may be problematic in the neurosurgical patient. The total use of
      systemic analgesia can be minimised with the use of regional techniques, such as
      local anaesthetic nerve blocks. A multimodal technique, using different agents,
      is most likely to be effective. 

PMID- 26203506
TI  - Coping with patient suicide and psychological debrief for nurses.

PMID- 26203507
TI  - Compression for chronic oedema: improving the patient experience.

PMID- 26203508
TI  - Creative scholarship: the importance of global networks.

PMID- 26203510
TI  - Can the NHS make the efficiency savings it needs to survive?

PMID- 26203509
TI  - Improving nursing research activity: the importance of leadership.

PMID- 26203511
TI  - Taking a global comparative view of patient safety and care quality.

PMID- 26203512
TI  - Relationships: from staff nurse to nurse consultant. Part 10: personality
      clashes.

PMID- 26203513
TI  - Airlines and creches can do it, why not a ward near you?

PMID- 26203515
TI  - ?

PMID- 26203514
TI  - ?

PMID- 26203516
TI  - ?

PMID- 26203517
TI  - ?

PMID- 26203518
TI  - ?

PMID- 26203519
TI  - Synthetic mononuclear nonheme iron-oxygen intermediates.
AB  - Mononuclear nonheme iron-oxygen species, such as iron-superoxo, -peroxo, 
      hydroperoxo, and -oxo, are key intermediates involved in dioxygen activation and
      oxidation reactions catalyzed by nonheme iron enzymes. Because these iron-oxygen
      intermediates are short-lived due to their thermal instability and high
      reactivity, it is challenging to investigate their structural and spectroscopic
      properties and reactivity in the catalytic cycles of the enzymatic reactions
      themselves. One way to approach such problems is to synthesize biomimetic iron
      oxygen complexes and to tune their geometric and electronic structures for
      structural characterization and reactivity studies. Indeed, a number of
      biologically important iron-oxygen species, such as mononuclear nonheme iron(III)
      superoxo, iron(III)-peroxo, iron(III)-hydroperoxo, iron(IV)-oxo, and iron(V)-oxo
      complexes, were synthesized recently, and the first X-ray crystal structures of
      iron(III)-superoxo, iron(III)-peroxo, and iron(IV)-oxo complexes in nonheme iron
      models were successfully obtained. Thus, our understanding of iron-oxygen
      intermediates in biological reactions has been aided greatly from the studies of
      the structural and spectroscopic properties and the reactivities of the synthetic
      biomimetic analogues. In this Account, we describe our recent results on the
      synthesis and characterization of mononuclear nonheme iron-oxygen complexes
      bearing simple macrocyclic ligands, such as N-tetramethylated cyclam ligand (TMC)
      and tetraamido macrocyclic ligand (TAML). In the case of iron-superoxo complexes,
      an iron(III)-superoxo complex, [(TAML)Fe(III)(O2)](2-), is described, including
      its crystal structure and reactivities in electrophilic and nucleophilic
      oxidative reactions, and its properties are compared with those of a
      chromium(III)-superoxo complex, [(TMC)Cr(III)(O2)(Cl)](+), with respect to its
      reactivities in hydrogen atom transfer (HAT) and oxygen atom transfer (OAT)
      reactions. In the case of iron-peroxo intermediates, an X-ray crystal structure
      of an iron(III)-peroxo complex binding the peroxo ligand in a side-on (eta(2))
      fashion, [(TMC)Fe(III)(O2)](+), is described. In addition, iron(III)-peroxo
      complexes binding redox-inactive metal ions are described and discussed in light
      of the role of redox-inactive metal ions in O-O bond activation in cytochrome c
      oxidase and O2-evolution in photosystem II. In the case of iron-hydroperoxo
      intermediates, mononuclear nonheme iron(III)-hydroperoxo complexes can be
      generated upon protonation of iron(III)-peroxo complexes or by hydrogen atom
      abstraction (HAA) of hydrocarbon C-H bonds by iron(III)-superoxo complexes.
      Reactivities of the iron(III)-hydroperoxo complexes in both electrophilic and
      nucleophilic oxidative reactions are described along with a discussion of O-O
      bond cleavage mechanisms. In the last section of this Account, a brief summary is
      presented of developments in mononuclear nonheme iron(IV)-oxo complexes since the
      first structurally characterized iron(IV)-oxo complex, [(TMC)Fe(IV)(O)](2+), was
      reported. Although the field of nonheme iron-oxygen intermediates (e.g., Fe-O2,
      Fe-O2H, and Fe-O) has been developed greatly through intense synthetic,
      structural, spectroscopic, reactivity, and theoretical studies in the communities
      of bioinorganic and biomimetic chemistry over the past 10 years, there is still
      much to be explored in trapping, characterizing, and understanding the chemical
      properties of the key iron-oxygen intermediates involved in dioxygen activation
      and oxidation reactions by nonheme iron enzymes and their biomimetic compounds. 

PMID- 26203520
TI  - Correspondence.

PMID- 26203521
TI  - Reply: To PMID 25380066.

PMID- 26203522
TI  - Knowledge brokering in public health: A critical analysis of the results of a
      qualitative evaluation.
AB  - Empirical data on the processes underlying knowledge brokering (KB)
      interventions, including their determining factors and effects, remain scarce.
      Furthermore, these interventions are rarely built on explicit theoretical
      foundations, making their critical analysis difficult, even a posteriori. For
      these reasons, it appeared relevant to revisit the results of a qualitative
      evaluation undertaken in the province of Quebec in parallel with a Canada-wide
      randomized controlled trial (RCT) evaluating various KB strategies in public
      health. This paper looks critically at the theoretical foundations of the KB
      interventions in light of two conceptual models: (1) the dissemination model
      underlying the KB interventions used in the Canadian trial and (2) a systemic KB
      model developed later. This critical analysis sheds light on the processes
      involved in KB interventions and the factors influencing their implementation and
      effects. The conclusions of the critical analysis are consistent with the
      systemic model, in which interpersonal contact is an essential condition for
      effective KB interventions. This analysis may advance knowledge in the field by
      enhancing our understanding of the role of knowledge brokers as essential
      mediators in KB processes and outcomes. 

PMID- 26203523
TI  - Testing the co-existence of two timing strategies for motor control in a unique
      task: The synchronisation spatial-tapping task.
AB  - The control of rhythmic action sequences may involve two distinct timing
      strategies, i.e., event-based and emergent timing, which are usually revealed
      through finger-tapping and circle-drawing tasks, respectively. There is a lively
      debate concerning the possibility of coexistence of the two modes of timing for
      the execution of a single task. If one considers emergent timing as simply an
      absence of explicit representation of a time interval, then by definition, the
      two modes of timing cannot coexist. However, if one considers that emergent
      timing engages control of another motor parameter, e.g., a control of movement
      through space rather than time, then the possibility of coexistence needs to be
      reassessed. In the present study, we designed a hybrid of finger-tapping and
      circle-drawing tasks for which the demands for space and time control were
      present at the same time in order to reassess the coexistence hypothesis. Seventy
      eight participants performed a spatial-tapping task in which finger taps were to
      be produced in synchrony with a regular metronome to 6 visual targets presented
      around a virtual circle. The metronome set ten distinct tempi (1100-300 ms).
      Using autocorrelation analyses on timing variables, we show that motor timing was
      event-based at slow tempi and emergent at faster tempi. Through an analysis of
      the trajectory, we confirm that an increase in the spatial control of movement
      took place congruently with a switch from event-based to emergent timing modes.
      At these fast tempi, timing and spatial errors were correlated but only at the
      specific target location for which a dynamical anchor point was revealed. Hence,
      we conclude that the coding of emergent timing has a spatial nature from which
      emerge timing regularities. This spatio-temporal strategy insures the performance
      of sequential motor actions when cognitive effort is too high for the use of pure
      event-based timing strategies.

PMID- 26203524
TI  - ?

PMID- 26203530
TI  - ?

PMID- 26203531
TI  - Index Band 36 - 2008.

PMID- 26203532
TI  - Size distribution and volume fraction of T(1) phase precipitates from TEM images:
      Direct measurements and related correction.
AB  - Transmission Electron Microscopy (TEM) can be used to measure the size
      distribution and volume fraction of fine scale precipitates in metallic systems.
      However, such measurements suffer from a number of artefacts that need to be
      accounted for, related to the finite thickness of the TEM foil and to the
      projected observation in two dimensions of the microstructure. We present a
      correction procedure to describe the 3D distribution of disc-like particles and
      apply this method to the plate-like T1 precipitates in an Al-Li-Cu alloy in two
      ageing conditions showing different particle morphologies. The precipitates were
      imaged in a High-Angular Annular Dark Field Microscope (HAADF-STEM). The
      corrected size distribution is further used to determine the precipitate volume
      fraction. Atom probe tomography (APT) is finally utilised as an alternative way
      to measure the precipitate volume fraction and test the validity of the electron
      microscopy results. 

PMID- 26203533
TI  - Synthesis of highly interconnected 3D scaffold from Arothron stellatus skin
      collagen for tissue engineering application.
AB  - The substrate which is avidly used for tissue engineering applications should
      have good mechanical and biocompatible properties, and all these parameters are
      often considered as essential for dermal reformation. Highly interconnected three
      dimensional (3D) wound dressing material with enhanced structural integrity was
      synthesized from Arothron stellatus fish skin (AsFS) collagen for tissue
      engineering applications. The synthesized 3D collagen sponge (COL-SPG) was
      further characterized by different physicochemical methods. The scanning electron
      microscopy analysis of the material demonstrated that well interconnected pores
      with homogeneous microstructure on the surface aids higher swelling index and
      that the material also possessed good mechanical properties with a Young's
      modulus of 0.89+/-0.2 MPa. Biocompatibility of the 3D COL-SPG showed 92% growth
      for both NIH 3T3 fibroblasts and keratinocytes. Overall, the study revealed that
      synthesized 3D COL-SPG from fish skin will act as a promising wound dressing in
      skin tissue engineering.

PMID- 26203534
TI  - Demographic and clinical correlates of suicidality in adolescents attending a
      specialist community mental health service: a naturalistic study.
AB  - BACKGROUND: Adolescents comprise a unique and often challenging group of patients
      with diverse presentations to the Mental Health Services; suicidal behavior being
      one of them. AIMS: The main aim of this naturalistic project was to investigate
      demographic and clinical correlates of adolescent suicidal and self-harm events,
      which may be of value to decision-making in clinical practice. METHOD: All
      adolescents (n = 149) registered and actively managed by a specialist community
      mental health service in South London were included in the study. Clinical
      information from their files was used to determine suicidality/self-harm events.
      The Columbia Classification Algorithm of Suicide Assessment (C-CASA) was utilised
      for classification purposes. Logistic regression was used to explore the effects
      of age, sex, diagnosis, medication, substance use (alcohol and/or cannabis) and
      ethnicity on suicidality/self-harming behaviors. RESULTS: Age, sex and use of
      psychotropic medication were identified to play a significant role in determining
      the risk of engaging in self-harming behavior. The risk was higher with
      increasing age and female sex. Medication seemed to have a protective effect.
      Reporting a 20% prevalence of non-suicidal self-injury (NSSI) in our population,
      we highlight the importance of NSSI as a distinct diagnostic category.
      CONCLUSIONS: Our findings have implications for risk assessment and appropriate
      decision-making in clinical settings. Results are translatable and relevant to
      other metropolitan areas.

PMID- 26203535
TI  - Safety of Uninterrupted Warfarin Therapy in Patients Undergoing Cardiovascular
      Endovascular Procedures: A Systematic Review and Meta-Analysis.
AB  - PURPOSE: To conduct a systematic review and meta-analysis of complication rates
      and outcomes in patients undergoing endovascular procedures who receive
      uninterrupted versus interrupted warfarin therapy. MATERIALS AND METHODS:
      Literature published between 1990 and 2014 was searched for reports of
      comparative studies of vascular procedures. Information on periprocedural
      complications and patient deaths less than 30 days after the procedure was
      extracted. A random effects model was used and odds ratios (ORs) were reported.
      An OR of less than 1 was considered to indicate lower risk of the outcome with
      uninterrupted warfarin therapy. Meta-analysis was conducted by using meta
      analysis software. RESULTS: A total of 27 studies of 20,376 patients were
      included. For arterial procedures, there were no significant differences between
      the uninterrupted and interrupted warfarin therapy groups in access site hematoma
      (OR, 0.59; 95% confidence interval [CI]: 0.33, 1.03; P = .06), any bleeding
      complications (OR, 0.56; 95% CI: 0.30, 1.06; P = .07), mortality (OR, 1.40; 95%
      CI: 0.37, 5.25; P = .62), intracranial hemorrhage (OR, 0.55; 95% CI: 0.03, 8.91;
      P = .68), ischemic stroke (OR, 0.85; 95% CI: 0.12, 5.84; P = .87), and major
      bleeding (OR, 0.56; 95% CI: 0.21, 1.51; P = .25). For venous procedures,
      uninterrupted warfarin was associated with lower odds of access site hematoma
      (OR, 0.70; 95% CI: 0.50, 0.99; P = .04), any bleeding complications (OR, 0.61;
      95% CI: 0.48, 0.77; P < .01), ischemic stroke (OR, 0.21; 95% CI: 0.10, 0.45; P <
      .01), and major bleeding (OR, 0.64; 95% CI: 0.51, 0.80; P < .01). For arterial
      and venous procedures combined, uninterrupted warfarin was associated with lower
      odds of access site hematoma (OR, 0.68; 95% CI: 0.51, 0.91; P = .01), bleeding
      complications (OR, 0.59; 95% CI: 0.48, 0.74; P < .01), ischemic stroke (OR, 0.25;
      95% CI: 0.12, 0.50; P < .01), and major bleeding (OR, 0.61; 95% CI: 0.49, 0.77; P
      < .01). Heterogeneity in most analyses was low, and confidence in the estimates
      was moderate. CONCLUSION: Uninterrupted perioperative warfarin therapy is safe
      for patients undergoing arterial procedures, but interrupted warfarin may be
      preferred for those undergoing venous procedures; no differences in outcome rates
      were found in the randomized controlled trials. Future studies should be
      performed to validate these results.

PMID- 26203536
TI  - Characterization of l-Digitoxosyl-phenanthroviridin from Streptomyces venezuelae
      ISP5230.
AB  - The jadomycin-derived compound l-digitoxosyl-phenanthroviridin was isolated from
      fermentations of Streptomyces venezuelae ISP5230 grown in nutrient-deficient
      media with l-lysine as the sole nitrogen source. Structural elucidation was
      accomplished using a combination of high-resolution MS, LC-MS/MS, and 1D- and 2D
      NMR. The compound was evaluated against the National Cancer Institute (NCI) 60
      human tumor cell line screen in both the one-dose and five-dose screens, and
      cytotoxicity was compared to a small library of jadomycin analogues to probe the
      structure-activity relationship. 

PMID- 26203537
TI  - The Isonzo front in the First World War: glass ampoules found in the vicinity of
      the village Kred.
AB  - OBJECTIVE: To identify the contents of ampoules stored items at the WW I Kobarid
      Museum, Slovenia. Sources and methods: Analysis of ampoules from the Kobarid
      Museum using pharmacopoeial methods. RESULTS: The contents of the unlabelled
      ampoules were identified as calcium hypochlorite, a decontaminant for mustard gas
      (Yperite). CONCLUSION: The Isonzo front/Soska fronta was opened on May 24 1915 by
      the Kingdom of Italy according to a secret London Treaty. In exchange for the
      opening of this front, the Kingdom of Italy would be granted large tracts of
      territory in the wesster provinces of the Austro-Hungarian Empire and along the
      Adriatic coast. The ensuing trench-warfare during the eleven Isonzo battles ended
      with the 12th battle known as the Kobarid/Karfeit/Caporetto break-thru in October
      1917. The joint German and Austro-Hungarian forces waged a massive gas-attack
      with dichloroarsine and phosgene, which was later disclosed as the horrifying
      overture to the general disordered retreat of the Italian troops to Piave. The
      possibility of a chemical attack was underestimated by the Italian high command
      as shown by the ineffective gas-masks issued to the troops. Hovewer, a recent
      find of ampoules with calcium hypochlorite at the village of Kred, now exhibited
      at the Kobarid WWI Museum, leads to the conclusion that the Italian IVth army's
      command, located in Kred, considered decontamination measures against Yperite
      necessary.

PMID- 26203538
TI  - An 18th century Tuscan pharmacy: analysis of the library.
AB  - The archival documents of San Luca Hospital, which has long been the most
      important welfarist institution of the Republic of Lucca (Tuscany), are stored in
      the Record Offices of Lucca. The hospital was served by a pharmacy, where the
      medicaments were prepared for patients and for the needs of other institutions in
      the city. Three different inventories, dating back to 1719, 1749 and 1784, report
      on a list of books hosted in the pharmacy. The identification and analysis of the
      works available in the library have allowed to reconstruct the tendencies of
      pharmacy thoughts and practices in Lucca during the 18th century. The library of
      the pharmacy of San Luca Hospital revealed the persistence of ancient medicine
      and of the pharmacy tradition, based mainly on the use of the simples. However,
      the influence of iatrochemistry, which following the paracelsian theories
      contributed to convert pharmacy from a botanical science to a chemical
      discipline, increased in the second half of the century, when the library was
      enriched with more recent works. The analysis of the inventories demonstrates the
      presence of both the galenic-arabic and chemical tradition, therefore reflecting
      an 18th century pharmacy supplied with a composite literature.

PMID- 26203539
TI  - Historical survey of the internal use of unprocessed amber.
AB  - The organic mineraloid gemstone, amber, a fossilized resin collected from Eocene
      deposits laid down around 44 million years old on the Baltic coast, has been an
      important geopharmaceutical in the western materia medica since classical times.
      Once rendered into powdered form, it could be delivered into the body using a
      wide range of vehicles including lozenges, pills, tablets, troches, electuaries,
      solutions and lohochs (lick-pots), and with toast and poached eggs. Acting either
      alone or in combination with a wide range of botanical, zoological and other
      geological ingredients, it was employed in the treatment of a huge range of
      diseases. Most prominent among these were various vascular disorders (e.g.
      haemoptysis, haemorrhage, excessive menstrual bleeding), problems with the
      urogenital system (e.g. tendency towards miscarriage, impotence, venereal
      diseases, strangury, dysuria and bladder stones) and alimentary conditions,
      particularly dysentery. A variety of infectious diseases, including plague,
      gonorrhoea, measles and fevers could be targeted with amber-containing
      preparations, as could epilepsy, melancholy and the ravages of old age. Rather
      more unusual applications included its use in the treatment of impotence,
      halitosis, drunkenness and a weak back.

PMID- 26203540
TI  - [Use of phytotherapy as a form of ethnoveterinary medicine in the area of Stara
      planina mountain in Serbia].
AB  - Ethnoveterinary medicine (EVM) considers implementation of folk knowledge and
      skills in animal health care, production and breeding. Also it means
      understanding of diagnostic, preventive, therapeutic skills and treatments in
      order to improve public health. EVM has a wide importance in the organic farming
      and environmental protection. Our studied geographic area is important because it
      is inhabited with Shops or Torlaks, a special ethnographic group of the South
      Slavs. Torlaks have developed special animal treatment and methods of animal
      breeding, particularly in sheep. The aim of this study was to examine the
      knowledge of ethno veterinary medicine in villagers from the eastern part of
      Stara planina in the Dimitrovgrad municipality, District of Pirot, to point out
      the specificity and importance of knowledge in relation to the geographic places
      and determine the applicability of knowledge in veterinary medicine and organic
      production. The research included 50 inhabitants from area of villages: Gornji
      Krivodol, Boljev Dol, Kamenica and Senokos. All villages are in the territory of
      the municipality of Dimitrovgrad, District of Pirot, Republic of Serbia.
      Performed methods were: non-structural, semi-structured and field interviews.
      According to the collected data, 64 different recipes and methods were noted, of
      which 43 include medicinal plants recipes, and other data include different
      methods of diagnosis, treatment, prevention and animal nutrition.

PMID- 26203541
TI  - The first case of pagophagia: the Byzantine Emperor Theophilus.
AB  - The Byzantine Emperor Theophilus (829-842 AD) died from dysentery, the exact
      nature of which is unknown. However, based on the original Greek texts of the
      Byzantine historians and chroniclers of that era, the possible cause of death may
      be connected to Theophilus' pagophagia (snow eating), in order to relieve the
      symptoms of gastric inflammation. Additionally to the symptoms from the gastro
      intestinal system, the Emperor seemed suffering from depress after the defeat of
      his army and the loss of territories, among whom his native town, Amorion. The
      current study supports the theoretical possibility that the case of pagophagia in
      the 9th century AD, so well described by a great number of historians because of
      the sufferer's royal identity, extends in the past the knowledge on pica, still
      attracting the medical interest.

PMID- 26203542
TI  - Neurosurgical contributions of Samuel D. Gross.
AB  - One of the most famous American Surgeons of the early 1800s was Samuel David
      Gross (1805-1884). His mastery of surgery was immortalized in Thomas Eakins' 1875
      painting of Gross titled The Gross Clinic. Gross was a prolific surgeon and one
      of his textbooks, a System of Surgery, went through 6 editions. Not known to many
      is the fact that this book also covered neurosurgical diseases and techniques.
      Gross was a skilled surgeon and able writer. His textbooks on surgery were well
      received in his day. Moreover, he should be considered an early pioneer of
      neurosurgery as his System of Surgery is filled with neurosurgical diagnoses and
      neurosurgical techniques.

PMID- 26203543
TI  - Pain: history, culture and philosophy.
AB  - Pain, one of the universals of existence, has a long and venerable history, its
      origin initially attributed to godly punishment for disbelievers; and, with
      improved understanding, to physical and psycho-social factors. "Pain is emotion
      or sensation?" has been a debatable issue. Razes developed pleasure-pain theory,
      founded on the theories of Socrates, Plato, Aristotle and Epicurus. Descartes'
      Dualism shifted the centre of pain from the heart to the brain but negated the
      psychological contribution to its pathogenesis. Gate Control Theory, fascinated
      with the idea of "neurological gates", highlighted the important role of the
      brain in dealing with the messages received. The International Association of the
      Study of Pain, in 1979, coined a definition of pain which is currently in use and
      was last updated on 6th October 2014. Its validity has been challenged and a new
      definition has been suggested. Whereas the experience is personalized,
      immeasurable and unsharable, different cultural groups react differently to pain
      from relative tolerance to over-reaction. Gender and ethnic differences in the
      perception of pain are well proven and the effects of various religious beliefs
      adequately scored. Despite extensive research over centuries, understanding of
      pain mechanisms is still far from optimal. Untiring efforts to identify a
      paincentre in the brain have been futile. Had it been possible, millions of pain
      sufferers would have been relieved of their physical agony and mental anguish by
      the prick of needle.

PMID- 26203544
TI  - The medical use of leeches in contemporary Spain: between science and tradition.
AB  - In Spain leeches have been used both in popular and scientific medicine
      throughout its history. In this study we analyze the historical fluctuations of
      leech therapy. At the start of the 20th century it was still being used in in
      scientific medicine, as can be seen in the treatment administered to German
      Gamazo, a minister during the reign of Alfonso XII and the regency of Archduchess
      Maria Christina of Austria, during a serious illness in 1901. Leech therapy was
      to fall dramatically into disuse and was to survive only in folk medicine, with
      leeches losing their reputation as a therapeutic agent. The data obtained is the
      result of a systematic review of the literature and of the major databases in the
      fields of folklore, ethnography, social anthropology and medical anthropology.
      Leeches have been used in Spanish folk medicine to treat ailments and disorders
      in up to 11 categories of the International Statistical Classification of
      Diseases and Related Health Problems (ICD-10), particularly in the treatment of
      diseases of the circulatory, respiratory and musculoskeletal systems. According
      to the available literature, they were part of the folk therapeutic arsenal, at
      least until the seventies of the last century. Our study also provides
      information about the medicinal use, commerce and consumption of these animals in
      recent years.

PMID- 26203545
TI  - A novel method to combat the cholera epidemic among the Romanian Army during the
      Balkan War - 1913.
AB  - The history of cholera, a specific infection caused by Vibrio Cholerae, starts in
      ancient times. The sixth pandemic that began in 1899 and lasted until 1923,
      started in India and came to Eastern Europe through Russia. The expansion of the
      epidemic in the Balkans was facilitated both by the 2 Balkan Wars and the First
      World War. Romania, as a participant in these wars was affected by cholera, which
      was especially common among the army during the Balkan War. If the original
      source of the cholera issue is still controversial, both Romanians and Bulgarians
      accusing each other of being the basis of the outbreaks south of the Danube, it
      is widely recognized that the extent of the disease was facilitated by the
      sanitary conditions of food preparation and drinking water sources among both
      Romanian soldiers and in the civilian population. Under these conditions, in
      addition to numerous measures against cholera taken by the Ministry of War, Prof.
      I. Cantacuzino successfully experiments outbreak vaccination for the first time
      in the world with a vaccine prepared by himself and his collaborators. The
      vaccine containing 25 breeds of vibriones was a success in terms of rapid
      development of a preparation, the application of which was achieved through a
      quick campaign and proved extremely efficient, imposing the Romanian method as an
      effective way to combat a disease in full outbreak.

PMID- 26203546
TI  - Giuseppe Moscati: a man, a physician and a scientist.
AB  - The life of Giuseppe Moscati (1880-1927) as a man, as a physician and as a
      scientist may be framed within the cultural climate of Positivism, which spread
      over the last years of the 19th century and the beginning of the 20th Century.
      His activity contributed to patients' care improvement; in addition to meticulous
      drug regimens, he also prescribed a methodology of spiritual care, involving
      meditation and self-control as part of an holistic approach to healthcare. Our
      review deals with his published researches, highlighting the innovative findings
      on the juvenile diabetes treatment and extensive clinical changes consequent upon
      nephritis. This extraordinary man put considerable emphasis on primary care and
      holistic health in Italy, pioneering a new patient-centred, and holistic approach
      to medicine.

PMID- 26203547
TI  - [Bordellos in Bjelovar's medical history].
AB  - The work is related to the existence of three Bjelovar Bordellos of early 20th
      century with epidemic/endemic existence of venereal disease, despite the then
      public health and police regulations. Conditions during the opening of the new
      bordello in Bjelovar in 1913 with architectonic pictures and reasons to close all
      three Bordellos.

PMID- 26203548
TI  - [Prof. Zdenko KriZan (1915-2005) - physician, anatomist and teacher].
AB  - Zdenko KriZan (1915 - 2005), physician, anatomist and teacher, is an important
      academic figure of the 20th century, especially in the South Slavic area. He
      participated in the founding of three anatomical institutes and directed their
      work. During the years of his career he was teaching and he did scientific
      research. Prof. KriZan is author of three compendia of anatomy for Medicine and
      Dentistry students. The results of his anatomical research, mainly in the area of
      the head skeleton and blood vessels, were published in national and international
      scientific journals. This article is a rewiew of prof. KriZan's biography data.

PMID- 26203549
TI  - Thirty years of the "Anica Bitenc Travelling Fellowship" - a tribute to Dr. Igor
      A.S. Bitenc.
AB  - Thirty years ago, in 1984, Dr. Igor A. S. Bitenc, M.D., F.R.C.S.(C), a retired
      orthopaedic surgeon from Canada, who was of Yugoslav descent, and who had always
      remained attached to his original homeland, founded a travelling fellowship for
      young orthopaedic surgeons from former Yugoslavia named the "Anica Bitenc
      Travelling Fellowship" after his late mother. The first Fellow visited Canada in
      1985 and was followed by five Fellows from different areas of Yugoslavia in
      successive years. Due to the tragic war in Yugoslavia in the 90's, the Fellowship
      was postponed for several years. It was resumed in 1997, but only for three newly
      formed states of Croatia, Slovenia and Serbia. Funding of the Fellowship was
      provided by an endowment from Dr. Bitenc and managed by the Canadian Orthopaedic
      Association, which hosts one Fellow per year on the rotational basis from
      Slovenia, Croatia and Serbia. The Fellowship finally proved to be very successful
      and, owing to the benevolence of Dr. Bitenc, 24 young orthopaedic surgeons from
      various regions of former Yugoslavia have had the opportunity to visit the best
      orthopaedic centres in Canada so far. Dr. Bitenc has ensured the Fellowship will
      continue for many years to come by bequeathing an endowment of $ 300.000. This
      unforgettable act of human nobility and patriotic sensibility will be of enormous
      help in future to many orthopaedic surgeons and their numerous patients in the
      countries of South Slavs.

PMID- 26203550
TI  - Caesarean section in Ancient Greek mythology.
AB  - The narrative of caesarean birth appears on several occasions in Greek mythology:
      in the birth of Dionysus is the God of the grape harvest and winemaking and wine;
      in the birth of Asclepius the God of medicine and healing; and in the birth of
      Adonis the God of beauty and desire. It is possible, however not obligatory, that
      it was not solely a fantasy but also reflected a contemporary medical practice.

PMID- 26203551
TI  - Liquid phase oxidation chemistry in continuous-flow microreactors.
AB  - Continuous-flow liquid phase oxidation chemistry in microreactors receives a lot
      of attention as the reactor provides enhanced heat and mass transfer
      characteristics, safe use of hazardous oxidants, high interfacial areas, and
      scale-up potential. In this review, an up-to-date overview of both technological
      and chemical aspects of liquid phase oxidation chemistry in continuous-flow
      microreactors is given. A description of mass and heat transfer phenomena is
      provided and fundamental principles are deduced which can be used to make a
      judicious choice for a suitable reactor. In addition, the safety aspects of
      continuous-flow technology are discussed. Next, oxidation chemistry in flow is
      discussed, including the use of oxygen, hydrogen peroxide, ozone and other
      oxidants in flow. Finally, the scale-up potential for continuous-flow reactors is
      described. 

PMID- 26203552
TI  - Distribution of Gemcitabine Is Nearly Homogenous in Two Orthotopic Murine Models
      of Pancreatic Cancer.
AB  - Pancreatic cancer is one of the leading causes of cancer-related death in the
      United States. Gemcitabine is a common treatment, but response rates are low,
      perhaps due in part to tumor hypoxia. We utilized (14)C-labeled gemcitabine to
      map distribution of the drug with respect to perfused and hypoxic regions of the
      tumor microenvironment in two orthotopic xenograft models of pancreatic cancer.
      There was only a slight reduction in gemcitabine in hypoxic areas, with ~78% of
      the drug present in hypoxic compared to perfused areas. In addition, only a 4%
      reduction in gemcitabine was measured at >100 MUm from perfused blood vessels.
      Thus, despite significant areas of hypoxia in these tumors, gemcitabine
      distribution is relatively homogenous. Ours is the first study to directly
      measure gemcitabine distribution within tumor tissue, demonstrating that in these
      models, tumor tissue does not represent a barrier to gemcitabine penetration. 

PMID- 26203553
TI  - Two sides of the same coin: Factors that support and challenge the wellbeing of
      refugees resettled in a small urban center.
AB  - For refugees who undergo permanent resettlement, characteristics of the
      resettlement context influence their ability to heal from pre-migration
      persecution and achieve a sense of wellbeing. This ethnographic study examines
      the impact of place-related determinants on the sense of wellbeing experienced by
      refugees resettled in a small urban center. The paper reports on the results of
      in-depth interviews that were conducted with ten former refugees in St. John's,
      Canada. We found that challenges and coping resources both emerged from the same
      aspects of the city, including its built environment, natural environment,
      history, culture, and low ethnic diversity. Future research should attend to how
      aspects of the resettlement context can simultaneously challenge and support
      refugees' sense of wellbeing. 

PMID- 26203554
TI  - Fast pyrolysis of eucalyptus waste in a conical spouted bed reactor.
AB  - The fast pyrolysis of a forestry sector waste composed of Eucalyptus globulus
      wood, bark and leaves has been studied in a continuous bench-scale conical
      spouted bed reactor plant at 500 degrees C. A high bio-oil yield of 75.4 wt.% has
      been obtained, which is explained by the suitable features of this reactor for
      biomass fast pyrolysis. Gas and bio-oil compositions have been determined by
      chromatographic techniques, and the char has also been characterized. The bio-oil
      has a water content of 35 wt.%, and phenols and ketones are the main organic
      compounds, with a concentration of 26 and 10 wt.%, respectively. In addition, a
      kinetic study has been carried out in thermobalance using a model of three
      independent and parallel reactions that allows quantifying this forestry waste's
      content of hemicellulose, cellulose and lignin.

PMID- 26203555
TI  - Proximal Capture Dynamics for a Single Biological Nanopore Sensor.
AB  - Single nanopore sensors enable capture and analysis of molecules that are driven
      to the pore entry from bulk solution. However, the distance between an analyte
      and the nanopore opening limits the detection efficiency. A theoretical basis for
      predicting particle capture rate is important for designing modified nanopore
      sensors, especially for those with covalently tethered reaction sites. Using the
      finite element method, we develop a soft-walled electrostatic block (SWEB) model
      for the alpha-hemolysin channel that produces a vector map of drift-producing
      forces on particles diffusing near the pore entrance. The maps are then coupled
      to a single-particle diffusion simulation to probe capture statistics and to
      track the trajectories of individual particles on the MUs to ms time scales. The
      investigation enables evaluation of the interplay among the electrophoretic,
      electroosmotic, and thermal driving forces as a function of applied potential.
      The findings demonstrate how the complex drift-producing forces compete with
      diffusion over the nanoscale dimensions of the pore. The results also demonstrate
      the spatial and temporal limitations associated with nanopore detection and offer
      a basic theoretical framework to guide both the placement and kinetics of
      reaction sites located on, or near, the nanopore cap. 

PMID- 26203556
TI  - Pycnogenol Protects Against Rotenone-Induced Neurotoxicity in PC12 Cells Through
      Regulating NF-kappaB-iNOS Signaling Pathway.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
      dopaminergic neurons degeneration and oxidative damage may underlie this process.
      However, there are still no efficient drugs to cure the disease. Pycnogenol (PYC)
      isolated from the procyanidin-rich French maritime pine (Pinus maritime) bark has
      shown various antioxidant activities in previous studies. In this study, we
      explored its effect against rotenone (Rot)-induced neurotoxicity and the
      underlying mechanisms in PC12 cells. Using Rot-induced cell model of PD, we found
      that PYC treatment significantly increased cell viability and decreased cell
      apoptosis in Rot-treated PC12 cells in a dose-dependent manner. Furthermore, data
      showed that PYC markedly reduced inducible nitric oxide synthase (iNOS)-nitric
      oxide (NO) signaling in Rot-treated PC12 cells. Pretreatment with the iNOS
      specific inhibitor significantly attenuated Rot-induced neurotoxicity. Moreover,
      PYC was found to be capable of reducing Rot-induced NF-kappaB activation.
      Blocking NF-kappaB signaling with its inhibitor mimicked the biological effect of
      PYC on Rot-induced iNOS and NO expression levels, as well as neurotoxicity in
      PC12 cells, suggesting that the NF-kappaB-iNOS signaling pathway was likely to
      participate in the PYC-mediated protective progress. Our results suggest that PYC
      protects against Rot-induced neurotoxicity in PC12 cells, and the mechanism may
      be associated with the downregulation of NF-kappaB-iNOS signaling pathway. 

PMID- 26203557
TI  - miR-200c dampens cancer cell migration via regulation of protein kinase A
      subunits.
AB  - Expression of miR-200c is a molecular switch to determine cellular fate towards a
      mesenchymal or epithelial phenotype. miR-200c suppresses the early steps of tumor
      progression by preventing epithelial-mesenchymal transition (EMT) and
      intravasation of tumor cells. Unraveling the underlying molecular mechanisms
      might pinpoint to novel therapeutic options. To better understand these
      mechanisms it is crucial to identify targets of miR-200c. Here, we employ a
      combination of quantitative proteomic and bioinformatic strategies to identify
      novel miR-200c targets. We identify and confirm two subunits of the central
      cellular kinase protein kinase A (PKA), namely PRKAR1A and PRKACB, to be directly
      regulated by miR-200c. Notably, siRNA-mediated downregulation of both proteins
      phenocopies the migratory behavior of breast cancer cells after miR-200c
      overexpression. Patient data from publicly accessible databases supports a miR
      200c-PKA axis. Thus, our study identifies the PKA heteroprotein as an important
      mediator of miR-200c induced repression of migration in breast cancer cells. By
      bioinformatics, we define a miRNA target cluster consisting of PRKAR1A, PRKAR2B,
      PRKACB, and COF2, which is targeted by a group of 14 miRNAs. 

PMID- 26203561
TI  - Conserved nematode signalling molecules elicit plant defenses and pathogen
      resistance.
AB  - Plant-defense responses are triggered by perception of conserved microbe
      associated molecular patterns (MAMPs), for example, flagellin or peptidoglycan.
      However, it remained unknown whether plants can detect conserved molecular
      patterns derived from plant-parasitic animals, including nematodes. Here we show
      that several genera of plant-parasitic nematodes produce small molecules called
      ascarosides, an evolutionarily conserved family of nematode pheromones. Picomolar
      to micromolar concentrations of ascr#18, the major ascaroside in plant-parasitic
      nematodes, induce hallmark defense responses including the expression of genes
      associated with MAMP-triggered immunity, activation of mitogen-activated protein
      kinases, as well as salicylic acid- and jasmonic acid-mediated defense signalling
      pathways. Ascr#18 perception increases resistance in Arabidopsis, tomato, potato
      and barley to viral, bacterial, oomycete, fungal and nematode infections. These
      results indicate that plants recognize ascarosides as a conserved molecular
      signature of nematodes. Using small-molecule signals such as ascarosides to
      activate plant immune responses has potential utility to improve economic and
      environmental sustainability of agriculture. 

PMID- 26203562
TI  - MicroRNA-203 represses selection and expansion of oncogenic Hras transformed
      tumor initiating cells.
AB  - In many mouse models of skin cancer, only a few tumors typically form even though
      many cells competent for tumorigenesis receive the same oncogenic stimuli. These
      observations suggest an active selection process for tumor-initiating cells.
      Here, we use quantitative mRNA- and miR-Seq to determine the impact of Hras(G12V)
      on the transcriptome of keratinocytes. We discover that microRNA-203 is
      downregulated by Hras(G12V). Using a knockout mouse model, we demonstrate that
      loss of microRNA-203 promotes selection and expansion of tumor-initiating cells.
      Conversely, restoration of microRNA-203 using an inducible model potently
      inhibits proliferation of these cells. We comprehensively identify microRNA-203
      targets required for Hras-initiated tumorigenesis. These targets include critical
      regulators of the Ras pathway and essential genes required for cell division.
      This study establishes a role for the loss of microRNA-203 in promoting selection
      and expansion of Hras mutated cells and identifies a mechanism through which
      microRNA-203 antagonizes Hras-mediated tumorigenesis. 

PMID- 26203564
TI  - Free-standing NiTi alloy nanowires fabricated by nanoskiving.
AB  - We report on free-standing NiTi alloy nanowires (120 nm * 75 nm) fabricated using
      a technique referred to as "nanoskiving", which complements conventional thin
      film sputter deposition with ultramicrotomy for thin sectioning. To date, the
      technique has been limited to pure metals without exploring metallic alloys.
      Leveraging the technique for the fabrication of shape memory alloy (SMA)
      nanostructures meets two critical requirements: compositional control (via film
      deposition) and controlled dimensions (via film deposition and programmable
      sectioning). Microstructure and composition analysis confirm continuity of the
      produced nanowires and Ni and Ti elemental uniformity. Free-standing NiTi
      nanowires are robust and remain intact throughout physical manipulation. The
      fabrication of NiTi alloy nanowires by nanoskiving will advance fundamental
      characterization of small scale SMA behavior. 

PMID- 26203563
TI  - Seasonal shift in timing of vernalization as an adaptation to extreme winter.
AB  - The requirement for vernalization, a need for prolonged cold to trigger
      flowering, aligns reproductive development with favorable spring conditions. In
      Arabidopsis thaliana vernalization depends on the cold-induced epigenetic
      silencing of the floral repressor locus FLC. Extensive natural variation in
      vernalization response is associated with A. thaliana accessions collected from
      different geographical regions. Here, we analyse natural variation for
      vernalization temperature requirement in accessions, including those from the
      northern limit of the A. thaliana range. Vernalization required temperatures
      above 0 degrees C and was still relatively effective at 14 degrees C in all the
      accessions. The different accessions had characteristic vernalization temperature
      profiles. One Northern Swedish accession showed maximum vernalization at 8
      degrees C, both at the level of flowering time and FLC chromatin silencing.
      Historical temperature records predicted all accessions would vernalize in autumn
      in N. Sweden, a prediction we validated in field transplantation experiments. The
      vernalization response of the different accessions was monitored over three
      intervals in the field and found to match that when the average field temperature
      was given as a constant condition. The vernalization temperature range of 0-14
      degrees C meant all accessions fully vernalized before snowfall in N. Sweden.
      These findings have important implications for understanding the molecular basis
      of adaptation and for predicting the consequences of climate change on flowering
      time. 

PMID- 26203566
TI  - [Global DNA methylation and homocysteine levels are lower in type 1 diabetes
      patients].
AB  - BACKGROUND: The worldwide rise in the incidence of Type 1 Diabetes (T1D), and the
      concordance rate between monozygotic twins (50%), indicate a strong effect of the
      environment as an underlying factor of this disease. This process can occur
      throughout epigenetic modifications of gene expression such as DNA methylation,
      in which several nutrients participate as cofactors. AIM: To determine DNA
      methylation status in T1D patients and if it is related to plasma levels of
      folates and homocysteine (Hcy). MATERIAL AND METHODS: We obtained blood samples
      from 25 T1D patients aged 13.7 +/- 5.9 years (11 males) and 25 healthy subjects
      aged 31.1 +/- 7.8 years (16 males). DNA methylation was measured using a
      colorimetric kit in extracted DNA. Results are expressed as median (interquartile
      range). RESULTS: Compared with healthy controls, T1D patients had lower global
      DNA methylation (0.85 (0.91) % and 1.25 (1.16) % respectively, p < 0.02) and Hcy
      levels (4.8 (1.1) umol/L and 7.3 (1.4) umol/L respectively p < 0.01). There were
      no differences in folate levels between groups. A significant association between
      folates and global DNA methylation status was observed in T1D patients (r = 
      0.564, p < 0.01) and healthy subjects (r = 0.440, p = 0.03). CONCLUSIONS: TD1
      patients had lower levels of Hcy and global DNA methylation. It is relevant to
      further investigate if this imbalance also induces epigenetic changes in a gene
      specific manner, especially in key genes involved in T1D pathogenesis.

PMID- 26203567
TI  - [Assessment of adherence to antihypertensive therapy].
AB  - BACKGROUND: Lack of adherence with medications is the main cause of
      antihypertensive treatment failure. AIM: To assess adherence to antihypertensive
      drugs and its determinants. MATERIAL AND METHODS: The Morinsky-Green
      questionnaire to determine treatment adherence was applied to 310 hypertensive
      patients from primary care centers, aged 60 +/- 10 years (65% females) in
      treatment for 4 +/- 1 months. Socio-demographic features, use of medications and
      quality of life using EQ5D questionnaire were also assessed. RESULTS: Twenty
      percent of patients were diabetic and 19% were smokers. Fifty four percent were
      adherent to therapy. A higher age and being unemployed were associated with a
      higher compliance. The main reasons to justify the lack of adherence were
      forgetting to take the pills in 67% and adverse effects in 10%. Only diastolic
      pressure was lower in adherent patients, compared with their non-adherent
      counterparts (78 +/- 12 and 81 +/- 17 mmHg, respectively p < 0.01). CONCLUSIONS:
      Only half of hypertensive patients comply with their antihypertensive therapy.

PMID- 26203568
TI  - [DRESS syndrome: Report of nine cases].
AB  - BACKGROUND: DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic
      Symptoms) is an uncommon disease caused by drugs. It is characterized by a
      polymorphic disseminated eruption with fever and multiple organ dysfunction. AIM:
      To report the etiology, characteristics, treatment, prognosis, and follow up of
      patients with DRESS Syndrome admitted to a clinical hospital. MATERIAL AND
      METHODS: Review of medical records of patients admitted for drug reactions,
      selecting those patients complying with clinical criteria for DRESS Syndrome.
      Drugs used during three months prior to the onset of symptoms were evaluated as
      possible causes of the disease. RESULTS: Nine patients aged 16 to 68 years (six
      males) complied with the clinical criteria for the disease. The causative
      medications were carbamazepine in three patients, phenytoin in three,
      antituberculous drugs in two and amoxicillin in one. All were treated with
      systemic steroids with a complete clinical resolution. CONCLUSIONS: DRESS
      syndrome is usually underdiagnosed and has a good response to systemic steroids.

PMID- 26203565
TI  - [Clinical predictors of bacteremia in immunocompetent adult patients hospitalized
      for community-acquired pneumonia].
AB  - BACKGROUND: The clinical usefulness of blood cultures in the management of
      patients hospitalized with community-acquired pneumonia (CAP) is controversial.
      AIM: To determine clinical predictors of bacteremia in a cohort of adult patients
      hospitalized for community-acquired pneumonia. MATERIAL AND METHODS: A
      prospective cohort of 605 immunocompetent adult patients aged 16 to 101 years
      (54% male) hospitalized for CAP was studied. The clinical and laboratory
      variables measured at admission were associated with the risk of bacteremia by
      univariate and multivariate analysis using logistic regression models. RESULTS:
      Seventy seven percent of patients had comorbidities, median hospital stay was 9
      days, 7.6% died in hospital and 10.7% at 30 days. The yield of the blood cultures
      was 12.6% (S. pneumoniae in 69 patients, H. influenzae in 3, Gram negative
      bacteria in three and S. aureus in one). These results modified the initial
      antimicrobial treatment in one case (0.2%). In a multivariate analysis, clinical
      and laboratory variables associated with increased risk of bacteremia were low
      diastolic blood pressure (Odds ratio (OR): 1.85, 95% confidence intervals (CI)
      1.02 to 3.36, p < 0.05), leukocytosis e" 15,000/mm3 (OR: 2.18, 95% CI 1.22 to
      3.88, p < 0.009), serum urea nitrogen e" 30 mg/dL (OR: 2.23, 95% CI 1.22 to 4.05,
      p < 0.009) and serum C-reactive protein e" 30 mg/dL (OR: 2.20, 95% CI 1.22 to
      3.97, p < 0.01). Antimicrobial use before hospital admission significantly
      decreased the blood culture yield (OR: 0.14, 95% CI 0.04 to 0.46, p < 0.002).
      CONCLUSIONS: Blood cultures do not contribute significantly to the initial
      management of patients hospitalized for community-acquired pneumonia. The main
      clinical predictors of bacteremia were antibiotic use, hypotension, renal
      dysfunction and systemic inflammation.

PMID- 26203569
TI  - [Skin manifestations in adults with a liver allograft].
AB  - BACKGROUND: Skin manifestations after liver transplantation are increasing due to
      long term immunosuppressive therapy along with an increase in patient survival.
      Several studies have reported dermatologic complications following renal
      transplant, but few have studied dermatologic problems after liver
      transplantation. AIMS: To describe the different types of cutaneous lesions
      encountered in adults receiving a liver allograft. To evaluate the frequency of
      cutaneous manifestations of patients in the liver transplant waiting list.
      MATERIAL AND METHODS: Eighty patients submitted to a liver transplant and 70
      patients in the liver transplant waiting list were evaluated with a complete
      dermatological physical examination. RESULTS: Sixty one percent of patients with
      a liver allograft had at least one skin manifestation. Of these, 34% had
      superficial fungal infections, 31% had viral infections, 20% had cutaneous side
      effects due to immunosuppressive treatment, 10% had malignant lesions, 2% had
      bacterial infections and one patient had a graft versus host disease. Only 28% of
      patients in the liver transplant waiting list had dermatologic problems, and the
      vast majority were lesions linked to liver cirrhosis. CONCLUSIONS: Cutaneous
      infections were the most common skin problems in liver transplant patients.
      Although neoplastic lesions are the most commonly mentioned lesions in the
      literature, only a 10% of our liver transplant patients presented these type of
      lesions.

PMID- 26203570
TI  - [Association between food addiction and nutritional status in Chilean college
      students].
AB  - BACKGROUND: High calorie foods, especially high in sugar and sodium may have an
      addictive potential. Experimental rats are able to develop symptoms and
      neurochemical changes, comparable to those observed in drug abuse, when they are
      exposed intermittently to sucrose. AIM: To evaluate the association between
      nutritional status and the prevalence of food addiction in Chilean college
      students. MATERIAL AND METHODS: Food addiction was assessed using the Yale Food
      Addiction Scale in 292 Chilean students aged 18-39 years (35% males). Height and
      weight were measured and body mass index (weight/height2) was calculated.
      RESULTS: Eleven percent of participants met the criteria for food addiction.
      Women had a higher prevalence than men (14.4% and 4.8%, respectively). Thirty
      percent of individuals with a body mass index over 30 kg/m2 met the criteria for
      food addiction. CONCLUSIONS: In these Chilean students, food addiction was more
      prevalent in women and a higher prevalence was observed in obese individuals.

PMID- 26203571
TI  - [Individual, social and environmental determinants of overweight and obesity
      among Chilean adolescents].
AB  - BACKGROUND: In Chile, overweight and obesity are pressing issues in public
      health. AIM: To identify individual, social and environmental factors that affect
      the likelihood of adolescents to become overweight or obese. MATERIAL AND
      METHODS: We used physical condition data of a sample of 900 urban eighth grade
      students from Santiago, obtained in the 2011 National Study of Physical
      Education. This information was complemented with georeferenced data from the
      place of residence of students and the environment in which they live. We used
      three logistic regression models to estimate the relationship between individual,
      social and environmental factors and the likelihood of being overweight or obese.
      RESULTS: Men and students of high socioeconomic status (SES) have a lower
      probability of being overweight (-6 percentage points (pp.) and -12 pp.
      respectively). Furthermore, the determinants that affect overweight depend on
      SES. Namely, only men of middle and low SES have a lower probability of being
      overweight (-7 pp.). Participation in school sporting activities reduces the
      likelihood of being overweight only for students of middle and low SES (-5,5
      pp.). For adolescents of high SES, the distance between their school and the
      nearest fast food restaurant decreases the likelihood of being overweight (-4.7
      pp. per km.). CONCLUSIONS: The determinants of overweight differ by SES. Public
      policy design should consider socioeconomic inequalities that characterize the
      Chilean reality.

PMID- 26203572
TI  - [The cost of polypharmacy in patients with type 2 diabetes mellitus].
AB  - BACKGROUND: Polypharmacy or the concomitant use of three or more medications, may
      increase the complexity of health care and its costs. AIM: To determine the costs
      of polypharmacy in patients with Type 2 Diabetes Mellitus in a Mexican population
      sample. PATIENTS AND METHODS: Analysis of health care costs in 257 patients with
      Type 2 Diabetes Mellitus from two family care facilities, who had at least five
      consultations during one year. The cost of professional care by family
      physicians, pharmacological care and medications were considered to calculate the
      total expenses. The price of medications and the number of units consumed in one
      year were used to determine pharmacological expenses. Medications were grouped to
      determine costs derived from complications and concomitant diseases. Costs were
      calculated in US dollars (USD). RESULTS: The mean cost derived from family
      physician fees was USD 82.32 and from pharmacy fees USD 29.37. The mean cost of
      medications for diabetes treatment was USD 33.31, for the management of
      complications USD 13.9 and for management of concomitant diseases USD 23.7,
      rendering a total cost of USD 70.92. Thus, the total annual care cost of a
      diabetic patient was USD 182.61. CONCLUSIONS: Medications represent less than 50%
      of total expenses of diabetic patients with polypharmacy.

PMID- 26203573
TI  - [Functional geriatric assessment in primary health care].
AB  - The functional assessment of moderately or severely dependent older people
      encompasses social, psychological and biological aspects that may influence their
      quality of life and their degree of independence. This paper reviews the global
      geriatric assessment that should be performed in primary health care (PHC) for
      moderately or severely dependent older people. Since 2012 in PHC in Chile, the
      norm establishes that the degree of independence of older people should be
      assessed using the Barthel scale and caregiver stress should be evaluated using
      Zarit scale. People with severe disability should receive home care. We recommend
      to evaluate also cognitive aspects using the Mini-Mental State Examination (MMSE)
      to Barthel Index or using the Functional Independence Measure (FIM), since they
      are closely associated with functional capacity.

PMID- 26203574
TI  - [Non-celiac gluten sensitivity: Another condition that responds to gluten].
AB  - Remission of gastrointestinal and general symptoms after gluten withdrawal has
      been described in some non-celiac individuals for nearly 30 years. Only recently,
      efforts have been made to define this entity, now referred to as "non-celiac
      gluten sensitivity". It includes patients that clinically respond to gluten free
      diet without exhibiting allergic or autoimmune features to explain such response.
      Wheat allergy, celiac disease, irritable bowel syndrome and symptoms induced by
      high FODMAPs (Fermentable, Oligo-, Di-, Mono-saccharides And Polyols) consumption
      are the main differential diagnoses. The relationship with neuropsychiatric
      disorders such as schizophrenia and autism has not been demonstrated, but
      currently it gives ground to great hope in families with affected children.
      Epidemiology of non-celiac gluten sensitivity is not clear. It is described as
      more common among women and less common in children. Genetic and immune factors,
      changes in intestinal microbiota and non-gluten components present in wheat
      grains are main factors postulated in the pathogenesis of this condition. To
      date, there are no specific biomarkers for non-celiac gluten sensitivity and
      diagnosis is reached by excluding other causes of disease. A trial with gluten
      free diet and subsequent gluten challenge is the methodology most frequently used
      to confirm diagnosis.

PMID- 26203575
TI  - [Causes and management of severe acute liver damage during pregnancy].
AB  - Abnormalities in liver function tests appear in 3% of pregnancies. Severe acute
      liver damage can be an exclusive condition of pregnancy (dependent or independent
      of pre-eclampsia) or a concomitant disease. HELLP syndrome and acute fatty liver
      of pregnancy are the most severe liver diseases associated with pregnancy. Both
      appear during the third trimester and have a similar clinical presentation. Acute
      fatty liver may be associated with hypoglycemia and HELLP syndrome is closely
      linked with pre-eclampsia. Among concomitant conditions, fulminant acute
      hepatitis caused by medications or virus is the most severe disease. Its clinical
      presentation may be hyper-acute with neurological involvement and severe
      coagulation disorders. It has a high mortality and patients should be
      transplanted. Fulminant hepatic failure caused by acetaminophen overdose can be
      managed with n-acetyl cysteine. Because of the high fetal mortality rate, the
      gestational age at diagnosis is crucial. 

PMID- 26203576
TI  - [Second Consensus of the Chilean Society of Endocrinology and Diabetes about
      insulin resistance].
AB  - Insulin resistance is a prevalent condition commonly associated with unhealthy
      lifestyles. It affects several metabolic pathways, increasing risk of
      abnormalities at different organ levels. Thus, diverse medical specialties should
      be involved in its diagnosis and treatment. With the purpose of unifying criteria
      about this condition, a scientific-based consensus was elaborated. A
      questionnaire including the most important topics such as cardio-metabolic risk,
      non-alcoholic fatty liver disease and polycystic ovary syndrome, was designed and
      sent to national experts. When no agreement among them was achieved, the Delphi
      methodology was applied. The main conclusions reached are that clinical findings
      are critical for the diagnosis of insulin resistance, not being necessary blood
      testing. Acquisition of a healthy lifestyle is the most important therapeutic
      tool. Insulin-sensitizing drugs should be prescribed to individuals at high risk
      of disease according to clinically validated outcomes. There are specific
      recommendations for pregnant women, children, adolescents and older people. 

PMID- 26203577
TI  - [An assessment of the Dundee Ready Education Environment Measure (DREEM) in
      Chilean university students].
AB  - BACKGROUND: The entry to a University requires an adaptation process that not all
      students solve with the same kind of success. Even though students social
      adaptation and emotional skills are essential, the educational environmental that
      they perceive has a significant influence in their academic life. AIM: To
      describe the changes in the perception about academic environment that medical
      students experience during the first three years of undergraduate career.
      MATERIAL AND METHODS: The Dundee Ready Education Environment Measure (DREEM)
      scale was applied to 525 first to third year medical students and an exploratory
      factorial analysis was made. RESULTS: Four factors were identified: Academic
      Perception: academic quality that students attribute to the process in which they
      take part, as well as to the assessment that they do of their learning outcomes
      (coefficient +/- = 0.85); Academic Experience: refers to positive emotions that
      students experience during the career such as confidence, pleasure and energy
      (coefficient +/- = 0.76); Atmosphere Perception, comfort and calm that students
      experiment during their academic activities (coefficient +/- = 0.79); Teachers
      Perception: the perception that students have of teachers about their interest
      and disposition towards students (coefficient +/- = 0.50). CONCLUSIONS: The
      assessment of academic environment quality is inversely associated with the lapse
      that the students have spent in their undergraduate careers.

PMID- 26203578
TI  - Maria Montessori (1870-1952): Women's emancipation, pedagogy and extra verbal
      communication.
AB  - Maria Montessori is one of the most well-known women in Italian history. Although
      she was the first woman who graduated in medicine in Italy, she is mostly known
      as an educator. Her teaching method--the Montessori Method- is still used
      worldwide--Because she could not speak English during the imprisonment in India,
      there was a big obstacle for her communication with children. However, the need
      to adopt a non-verbal communication, led her to a sensational discovery: children
      use an innate and universal language. This language, made of gestures and mimic,
      is called extra verbal communication.

PMID- 26203579
TI  - [Spontaneous clearance of hepatitis C virus after liver transplantation: Report
      of two cases].
AB  - The spontaneous clearance of hepatitis C virus infection is rare, especially
      after liver transplantation, condition in which recurrence is almost universal.
      We report two cases in which clearance of the virus was achieved after liver
      transplantation. We reviewed the literature and described possible mechanisms
      explaining this phenomenon, with emphasis on therapeutic implications. 

PMID- 26203581
TI  - [Left hepatic artery (LHA) emerging from the gastroduodenal artery: Report of one
      case].
AB  - Anatomic variations of the hepatic artery, which occur in 30 to 50% of patients,
      are a very important factor to be considered for Whipple procedure. The most
      common variations are those coming from the superior mesenteric artery, left
      gastric artery and the aorta. We report a 58-year-old woman with a story of one
      month of epigastric pain, jaundice and progressive itching. Magnetic resonance
      imaging showed a mass in the head of the pancreas. During pancreatoduodenectomy a
      left hepatic artery (LHA) emerging from the gastroduodenal artery and an
      accessory LHA emerging from the left gastric artery, were observed. The rest of
      the surgery was performed with no incidents. The patient had an uneventful
      postoperative evolution. 

PMID- 26203580
TI  - [Treatment of a severe Clostridium difficile infection with colonic lavages.
      Report of one case].
AB  - A loop ileostomy with intraoperative anterograde colonic lavage has been
      described as an alternative to colectomy in the management of cases of
      Clostridium difficile infection refractory to medical treatment. We report a 69
      years old diabetic women admitted with a septic shock. An abdominal CAT scan
      showed a pan-colitis that seemed to be infectious. A polymerase chain reaction
      was positive for Clostridium Difficile. Due to the failure to improve after full
      medical treatment, a derivative loop ileostomy and intra-operatory colonic lavage
      were performed, leaving a Foley catheter in the proximal colon. In the
      postoperative period, anterograde colonic instillations of Vancomycin flushes
      through the catheter were performed every 6 hours. Forty eight hours after
      surgery, the patient improved. A colonoscopy prior to discharge showed resolution
      of the pseudomembranous colitis. 

PMID- 26203582
TI  - [Resilience, Poverty and Rurality].

PMID- 26203583
TI  - [The National Health Survey of Chile gives useful information to health policy
      planning: Analysis of Diabetic Nephropathy as an index of potential saving].

PMID- 26203584
TI  - [Serious adverse effects of law No. 20.584].

PMID- 26203586
TI  - High School Completion Programs: A Community Guide Systematic Economic Review.
AB  - CONTEXT: On-time high school graduation rate is among the 26 leading health
      indicators for Healthy People 2020. High school completion (HSC) programs aim to
      increase the likelihood that students finish high school and receive a high
      school diploma or complete a GED (General Educational Development) program. This
      systematic review was conducted to determine the economic impact of HSC
      interventions, assess variability in cost-effectiveness of different types of
      programs, and compare the lifetime benefit of completing high school with the
      cost of intervention. EVIDENCE ACQUISITION: Forty-seven included studies were
      identified from 5303 articles published in English from January 1985 to December
      2012. The economic evidence was summarized by type of HSC program. All monetary
      values were expressed in 2012 US dollars. The data were analyzed in 2013.
      EVIDENCE SYNTHESIS: Thirty-seven studies provided estimates of incremental cost
      per additional high school graduate, with a median cost for HSC programs of $69
      800 (interquartile interval = $35 900-$130 300). Cost-effectiveness ratios varied
      depending on intervention type, study settings, student populations, and costing
      methodologies. Ten studies estimated the lifetime difference of economic benefits
      between high school nongraduates and graduates; 4 used a governmental perspective
      and reported benefit per additional high school to range from $187 000 to $240
      000; 6 used a societal perspective and reported a range of $347 000 to $718 000.
      Benefits exceeded costs in most studies from a governmental perspective and in
      all studies from a societal perspective. CONCLUSION: Interventions to increase
      HSC rates produce substantial economic benefits to government and society
      including averted health care costs. From a societal perspective, the benefits
      also exceed costs, implying a positive rate of return from investment in HSC
      programs.

PMID- 26203585
TI  - Chemotherapy Near the End of Life: First--and Third and Fourth (Line)--Do No
      Harm.

PMID- 26203587
TI  - Tanshinone IIA Facilitates TRAIL Sensitization by Up-regulating DR5 through the
      ROS-JNK-CHOP Signaling Axis in Human Ovarian Carcinoma Cell Lines.
AB  - Tanshinone IIA (TIIA) extracted from Salvia miltiorrhiza has been shown to
      possess antitumor and TRAIL-sensitizing activity. The involvement of DR5 in the
      mechanism whereby TIIA exerts its effects is unknown. This study aimed to explore
      the mechanism underlying TIIA augmentation of TRAIL-induced cell death in ovarian
      carcinoma cells. Cell viability was determined by MTS assay. Real-time RT-PCR and
      Western blotting were used to assess the mRNA and protein expression of relating
      signaling proteins. Transcriptional activation was explored by a dual-luciferase
      reporter assay. We found that TIIA sensitized human ovarian carcinoma cells to
      TRAIL-induced extrinsic apoptosis. Combined treatment with subtoxic
      concentrations of TIIA and TRAIL was more effective than single treatments with
      respect to cytotoxicity, clonogenic inhibition, and the induction of caspase-8
      and PARP activity in ovarian carcinoma cell lines TOV-21G and SKOV3. TIIA induced
      DR5 protein and mRNA expression in a concentration-dependent manner. DR5/Fc
      treatment markedly suppressed the TRAIL cytotoxicity enhanced by TIIA. These
      results indicate that DR5 plays an essential role in TIIA-induced TRAIL
      sensitization and that induction of DR5 by TIIA is mediated through the up
      regulation of CCAAT/enhancer-binding protein homologous protein (CHOP). Knockdown
      of CHOP gene expression by shRNA attenuated DR5 up-regulation and rescued cell
      viability under the treatment of TIIA-TRAIL combination. TIIA promoted JNK
      mediated signaling to up-regulated CHOP and thereby inducing DR5 expression as
      shown by the ability of a JNK inhibitor to potently suppress the TIIA-mediated
      activation of CHOP and DR5. In addition, the quenching of ROS using NAC prevented
      the induction of JNK phosphorylation and CHOP induction. Furthermore, inhibition
      of ROS by NAC significantly attenuated TRAIL sensitization by TIIA. Taken
      together, these data suggest that TIIA enhances TRAIL-induced apoptosis by
      upregulating DR5 receptors through the ROS-JNK-CHOP signaling axis in human
      ovarian carcinoma cells. 

PMID- 26203588
TI  - Usability of clinical decision support system as a facilitator for learning the
      assistive technology adaptation process.
AB  - The aim of this study was to evaluate the usability of Ontology Supported
      Computerized Assistive Technology Recommender (OSCAR), a Clinical Decision
      Support System (CDSS) for the assistive technology adaptation process, its impact
      on learning the matching process, and to determine the relationship between its
      usability and learnability. Two groups of expert and novice clinicians (total, n
      = 26) took part in this study. Each group filled out system usability scale (SUS)
      to evaluate OSCAR's usability. The novice group completed a learning
      questionnaire to assess OSCAR's effect on their ability to learn the matching
      process. Both groups rated OSCAR's usability as "very good", (M [SUS] = 80.7, SD
      = 11.6, median = 83.7) by the novices, and (M [SUS] = 81.2, SD = 6.8, median =
      81.2) by the experts. The Mann-Whitney results indicated that no significant
      differences were found between the expert and novice groups in terms of OSCAR's
      usability. A significant positive correlation existed between the usability of
      OSCAR and the ability to learn the adaptation process (rs = 0.46, p = 0.04).
      Usability is an important factor in the acceptance of a system. The successful
      application of user-centered design principles during the development of OSCAR
      may serve as a case study that models the significant elements to be considered,
      theoretically and practically in developing other systems. Implications for
      Rehabilitation Creating a CDSS with a focus on its usability is an important
      factor for its acceptance by its users. Successful usability outcomes can impact
      the learning process of the subject matter in general, and the AT prescription
      process in particular. The successful application of User-Centered Design
      principles during the development of OSCAR may serve as a case study that models
      the significant elements to be considered, theoretically and practically. The
      study emphasizes the importance of close collaboration between the developers and
      the end users.

PMID- 26203590
TI  - Switching of charged inverse micelles in non-polar liquids.
AB  - The electrodynamics of micellar ions in nonpolar liquids are well understood for
      the case that a voltage is applied or switched off. In this work, the
      electrodynamics of charged inverse micelles (CIMs) are studied when the applied
      voltage is switched to the opposite polarity, which is relevant for applications
      such as electrophoretic displays and liquid toner printing. Transient current
      measurements are used to characterize the switching of CIMs formed in a solution
      of surfactant polyisobutylene succinimide in n-dodecane. For reverse voltages
      with amplitude below 10V the measurements are in good agreement with a drift and
      diffusion model, confirming the established understanding of CIMs in nonpolar
      liquids. When the charge content is high, the reversal current shows a
      characteristic peak which is explained on the basis of dynamic space-charge
      effects. However, for reverse voltages larger than 10V, the transient currents
      are influenced by electrohydrodynamic flow in the liquid causing the CIMs to
      switch faster than predicted by the model. The occurrence of electrohydrodynamic
      flow is verified by optical tracking of tracer particles. Also, when the
      polarizing voltage is applied for longer times, an additional current peak
      emerges which is due to the accumulation of newly generated charges at the
      electrodes. 

PMID- 26203589
TI  - Solid-state encapsulation of Ag and sulfadiazine on zeolite Y carrier.
AB  - HYPOTHESIS: A new simplified procedure for encapsulation of antibacterial silver
      nanoparticles by Solid-state Ion Exchange (SSIE) procedure over zeolite Y,
      followed by deposition of sulfadiazine (SD) by dry mixing was examined for the
      preparation of topical antibacterial formulations. The ion-exchange and
      adsorptive properties of the zeolite matrix were utilized for the bactericidal Ag
      deposition and loading of antibiotic sulfadiazine. EXPERIMENTS: Assessment of the
      encapsulation efficiency of both active components loaded by solid and liquid
      deposition methods was made by X-ray diffraction, TEM, FT-IR spectroscopy and
      thermogravimetric analysis (TGA). SD release kinetics was also determined.
      FINDINGS: Sustained delivery of sulfadiazine has been observed from the Ag
      modified zeolites compared to the parent HY material. It was found that if SD was
      loaded in solution, part of the zeolite silver ions was released and interacted
      with SD, forming AgSD. By solid-state SD deposition, the reaction between the
      drug and the silver was restricted within the limits of inter-atomic interaction,
      and total but prolonged drug release occurred.

PMID- 26203591
TI  - Nanosilica-induced high mechanical strength of nanocomposite hydrogel for killing
      fluids.
AB  - Nano-silica was introduced to enhance the mechanical strength of polymer
      hydrogels obtained via the crosslinking of polyacrylamide (PAM) and chromium
      acetate. Rheological properties, compression strength and compressive stress
      strain of both nanocomposite and normal hydrogels without nano-silica were
      investigated by HAKKE rheometer, compression strength test device and electronic
      universal material testing machine. Moreover, environmental scanning electronic
      microscopic (ESEM) was adopted to observe the three-dimension network structure
      of nanocomposite and normal hydrogel, as well as the distribution of nano-silica.
      The results demonstrated that elastic moduli (G') and viscous moduli (G") of
      nanocomposite hydrogel were both improved with increasing nano-silica
      concentration. Especially when silica content reached 10wt%, G' and G" of
      nanocomposite hydrogel increased over one hundred times higher than those of
      normal hydrogel. The original compression strength of hydrogel was 70.8kPam(-1),
      while the resulting strength of nanocomposite was enhanced to be 196.64kPam(-1).
      When the hydrogel were sheared, the normal hydrogel was fractured under low
      strain, whereas nanocomposite hydrogel was not broken under high strain, and it
      quickly recovered its original shape after the release of load. In addition, the
      ESEM images indicated that a large quantity of silica particles aggregated and
      attached around the polymer chains, and others aggregated to fill into the three
      dimension network of hydrogel, which induced the compaction of the space between
      the network layers and reduced the flowing of free water wrapped in the network,
      therefore the mechanical strength of hydrogel was enhanced. 

PMID- 26203592
TI  - The impact of trough geometry on film shape. A theoretical study of droplets
      containing polymer, for P-OLED display applications.
AB  - For P-OLED display fabrication, it is important to control the final film shape,
      arising from drying of volatile droplets containing polymer. Due to peripheral
      pinning and subsequent outward capillary flow, a coffee-ring typically develops.
      This is inconvenient since a spatially uniform height, above the substrate, is
      required to ensure uniform current across the device. Typically the droplets are
      deposited inside a trough-like structure on the substrate. We present a thin-film
      lubrication model that tracks the drying dynamics through to the final film
      shape. The governing equations are derived and solved numerically. We investigate
      the effect of the trough's depth and the slope of the walls. Increasing the depth
      or the wall's gradient increases coffee-ring formation. This is due to an
      increase in horizontal velocity, caused by the substrate's shape as well as
      delayed gelation of the polymer. The latter allows the outward capillary flow to
      act for a longer time, before the height becomes fixed. 

PMID- 26203593
TI  - In Situ Detection of Active Edge Sites in Single-Layer MoS2 Catalysts.
AB  - MoS2 nanoparticles are proven catalysts for processes such as
      hydrodesulfurization and hydrogen evolution, but unravelling their atomic-scale
      structure under catalytic working conditions has remained significantly
      challenging. Ambient pressure X-ray Photoelectron Spectroscopy (AP-XPS) allows us
      to follow in situ the formation of the catalytically relevant MoS2 edge sites in
      their active state. The XPS fingerprint is described by independent contributions
      to the Mo 3d core level spectrum whose relative intensity is sensitive to the
      thermodynamic conditions. Density Functional Theory (DFT) is used to model the
      triangular MoS2 particles on Au(111) and identify the particular sulphidation
      state of the edge sites. A consistent picture emerges in which the core level
      shifts for the edge Mo atoms evolve counterintuitively toward higher binding
      energies when the active edges are reduced. The shift is explained by a
      surprising alteration in the metallic character of the edge sites, which is a
      distinct spectroscopic signature of the MoS2 edges under working conditions. 

PMID- 26203594
TI  - The highest-ranking rooster has priority to announce the break of dawn.
AB  - The "cock-a-doodle-doo" crowing of roosters, which symbolizes the break of dawn
      in many cultures, is controlled by the circadian clock. When one rooster
      announces the break of dawn, others in the vicinity immediately follow. Chickens
      are highly social animals, and they develop a linear and fixed hierarchy in small
      groups. We found that when chickens were housed in small groups, the top-ranking
      rooster determined the timing of predawn crowing. Specifically, the top-ranking
      rooster always started to crow first, followed by its subordinates, in descending
      order of social rank. When the top-ranking rooster was physically removed from a
      group, the second-ranking rooster initiated crowing. The presence of a dominant
      rooster significantly reduced the number of predawn crows in subordinates.
      However, the number of crows induced by external stimuli was independent of
      social rank, confirming that subordinates have the ability to crow. Although the
      timing of subordinates' predawn crowing was strongly dependent on that of the top
      ranking rooster, free-running periods of body temperature rhythms differed among
      individuals, and crowing rhythm did not entrain to a crowing sound stimulus.
      These results indicate that in a group situation, the top-ranking rooster has
      priority to announce the break of dawn, and that subordinate roosters are patient
      enough to wait for the top-ranking rooster's first crow every morning and thus
      compromise their circadian clock for social reasons. 

PMID- 26203595
TI  - Conversion of Carbon Dioxide to Methanol Using a C-H Activated Bis(imino)pyridine
      Molybdenum Hydroboration Catalyst.
AB  - Using a multistep synthetic pathway, a bis(imino)pyridine (or pyridine diimine,
      PDI) molybdenum catalyst for the selective conversion of carbon dioxide into
      methanol has been developed. Starting from ((Ph2PPr)PDI)Mo(CO), I2 addition
      afforded [((Ph2PPr)PDI)MoI(CO)][I], which features a seven-coordinate Mo(II)
      center. Heating this complex to 100  degrees C under vacuum resulted in CO loss
      and the formation of [((Ph2PPr)PDI)MoI][I]. Reduction of [((Ph2PPr)PDI)MoI][I] in
      the presence of excess K/Hg yielded (kappa(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH
      following methylene group C-H activation at the alpha-position of one PDI imine
      substituent. The addition of CO2 to (kappa(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH
      resulted in facile insertion to generate the respective eta(1)-formate complex,
      (kappa(6)-P,N,N,N,C,P-(Ph2PPr)PDI)Mo(OCOH). When low pressures of CO2 were added
      to solutions of (kappa(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH containing pinacolborane,
      the selective formation of H3COBPin and O(BPin)2 was observed along with
      precatalyst regeneration. When HBPin was limited, H2C(OBPin)2 was observed as an
      intermediate and (kappa(6)-P,N,N,N,C,P-(Ph2PPr)PDI)Mo(OCOH) remained present
      throughout CO2 reduction. The hydroboration of CO2 to H3COBPin was optimized and
      97% HBPin utilization by 0.1 mol % (kappa(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH was
      demonstrated over 8 h at 90  degrees C, resulting in a methoxide formation
      turnover frequency (TOF) of 40.4 h(-1) (B-H utilization TOF = 121.2 h(-1)).
      Hydrolysis of the products and distillation at 65  degrees C allowed for MeOH
      isolation. The mechanism of (kappa(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH mediated CO2
      hydroboration is presented in the context of these experimental observations.
      Notably, (kappa(6)-P,N,N,N,C,P-(Ph2PPr)PDI)MoH is the first Mo hydroboration
      catalyst capable of converting CO2 to MeOH, and the importance of this study as
      it relates to previously described catalysts is discussed. 

PMID- 26203597
TI  - Fructose and liver function--is this behind nonalcoholic liver disease?
AB  - PURPOSE OF REVIEW: The purpose was to summarize recent advances in the
      understanding of nonalcoholic fatty liver disease (NAFLD) pathophysiology and the
      role of fructose in NAFLD. RECENT FINDINGS: Epidemiological studies continue to
      point to a strong association between high fructose intake and NAFLD and its
      severity. New studies of NAFLD reveal the importance of upregulated de novo
      lipogenesis as a key feature in its pathophysiology along with increased visceral
      adiposity and alteration of gut microbiome. Studies of fructose in NAFLD show how
      this nutrient may uniquely exacerbate the phenotype of NAFLD. The timing of
      exposure to fructose may be important with early (in utero) exposure being
      particularly harmful. SUMMARY: Fructose is a potentially modifiable environmental
      exposure that appears to exacerbate NAFLD through multiple mechanisms. Although
      larger, longer clinical studies are still needed, it appears that limitation of
      fructose sources in the diet is beneficial in NAFLD.

PMID- 26203596
TI  - Structural and dynamic insights into the energetics of activation loop
      rearrangement in FGFR1 kinase.
AB  - Protein tyrosine kinases differ widely in their propensity to undergo
      rearrangements of the N-terminal Asp-Phe-Gly (DFG) motif of the activation loop,
      with some, including FGFR1 kinase, appearing refractory to this so-called 'DFG
      flip'. Recent inhibitor-bound structures have unexpectedly revealed FGFR1 for the
      first time in a 'DFG-out' state. Here we use conformationally selective
      inhibitors as chemical probes for interrogation of the structural and dynamic
      features that appear to govern the DFG flip in FGFR1. Our detailed structural and
      biophysical insights identify contributions from altered dynamics in distal
      elements, including the alphaH helix, towards the outstanding stability of the
      DFG-out complex with the inhibitor ponatinib. We conclude that the alphaC-beta4
      loop and 'molecular brake' regions together impose a high energy barrier for this
      conformational rearrangement, and that this may have significance for maintaining
      autoinhibition in the non-phosphorylated basal state of FGFR1. 

PMID- 26203599
TI  - Recent strategies to develop self-healable crosslinked polymeric networks.
AB  - Autonomous self-healable crosslinked materials designed with built-in ability to
      repair physical damage and cracks can prevent catastrophic failure and thus
      extend the lifetime of materials. They also retain their dimensional stability,
      mechanical strength, thermal stability, and solvent resistance. These features
      promote the development of effective self-healing materials for various
      applications. This review summarizes recent advances in the development of novel
      self-healable polymeric materials, both through extrinsic methods involving the
      encapsulation of extra healing agents in microcapsules and through intrinsic
      methods utilizing the formation of reversible chemical or physical crosslinks.
      Further, the outlook is briefly discussed on the important aspects for the
      current and future development of self-healable materials. 

PMID- 26203598
TI  - Changing Epidemiology of the Respiratory Bacteriology of Patients With Cystic
      Fibrosis.
AB  - BACKGROUND: Monitoring potential changes in the epidemiology of cystic fibrosis
      (CF) pathogens furthers our understanding of the potential impact of
      interventions. METHODS: We performed a retrospective analysis using data reported
      to the Cystic Fibrosis Foundation Patient Registry (CFFPR) from 2006 to 2012 to
      determine the annual percent changes in the prevalence and incidence of selected
      CF pathogens. Pathogens included Pseudomonas aeruginosa, methicillin-susceptible
      Staphylococcus aureus (MSSA), methicillin-resistant S aureus (MRSA), Haemophilus
      influenzae, Burkholderia cepacia complex, Stenotrophomonas maltophilia, and
      Achromobacter xylosoxidans. Changes in nontuberculous mycobacteria (NTM)
      prevalence were assessed from 2010 to 2012, when the CFFPR collected NTM species.
      RESULTS: In 2012, the pathogens of highest prevalence and incidence were MSSA and
      P aeruginosa, followed by MRSA. The prevalence of A xylosoxidans and B cepacia
      complex were relatively low. From 2006 to 2012, the annual percent change in
      overall (as well as in most age strata) prevalence and incidence significantly
      decreased for P aeruginosa and B cepacia complex, but significantly increased for
      MRSA. From 2010 to 2012, the annual percent change in overall prevalence of NTM
      and Mycobaterium avium complex increased. CONCLUSIONS: The epidemiology of CF
      pathogens continues to change. The causes of these observations are most likely
      multifactorial and include improvements in clinical care and infection prevention
      and control. Data from this study will be useful to evaluate the impact of new
      therapies on CF microbiology.

PMID- 26203600
TI  - Risk factors affecting the development of nephrocalcinosis, the most common
      complication of hypophosphatemic rickets.
AB  - The aim of the present study was to analyse the effects of combined treatment
      with calcitriol and phosphate, to find out the incidence of the nephrocalcinosis,
      and to elucidate the risk factor of nephrocalcinosis in patients with
      hypophosphatemic rickets. We followed six patients. The median age at diagnosis
      was 3.25 (0.75-10.5) years. The median follow-up duration was 8.25 (3.5-12.5)
      years. The mean dose of calcitriol and phosphate treatments was 39.1+/-8
      ng/kg/day, 90.5+/-57.1 mg/kg/day, respectively. Nephrocalcinosis was detected in
      three patients (50%). The mean dose of phosphate taken by the patients found to
      have nephrocalcinosis was detected to be high with a statistically significant
      difference (p=0.041). No significant relationship was found the mean dose of
      calcitriol. We found no relationship between the development of nephrocalcinosis
      and the incidence of hypercalciuria or hypercalcemia episodes. We found the
      increased phosphate dose administered for treatment to play a role in
      nephrocalcinosis development. 

PMID- 26203601
TI  - Comparison of energy expenditure, body composition, metabolic disorders, and
      energy intake between obese children with a history of craniopharyngioma and
      children with multifactorial obesity.
AB  - Craniopharyngioma is a histologically benign brain malformation with a
      fundamental role in satiety modulation, causing obesity in up to 52% of patients.
      AIM: To evaluate cardiovascular risk factors, body composition, resting energy
      expenditure (REE), and energy intake in craniopharyngioma patients and to compare
      the data with those from children with multifactorial obesity. POPULATION: All
      obese children and adolescents who underwent craniopharyngioma resection and a
      control group of children with multifactorial obesity in follow-up between May
      2012 and April 2013. MATERIALS AND METHODS: Anthropometric measurements,
      bioelectrical impedance, indirect calorimetry, energy intake, homeostatic model
      assessment insulin resistance (HOMA-IR), and dyslipidemia were evaluated.
      RESULTS: Twenty-three patients with craniopharyngioma and 43 controls were
      included. Children with craniopharyngioma-related obesity had a lower fat-free
      mass percentage (62.4 vs. 67.5; p=0.01) and a higher fat mass percentage (37.5
      vs. 32.5; p=0.01) compared to those with multifactorial obesity. A positive
      association was found between %REE and %fat-free mass in subjects with
      multifactorial obesity (68+/-1% in normal REE vs. 62.6+/-1% in low REE; p=0.04),
      but not in craniopharyngioma patients (62+/-2.7 in normal REE vs. 61.2+/-1.8% in
      low REE; p=0.8). No differences were found in metabolic involvement or energy
      intake. CONCLUSIONS: REE was lower in craniopharyngioma patients compared to
      children with multifactorial obesity regardless of the amount of fat-free mass,
      suggesting that other factors may be responsible for the lower REE.

PMID- 26203602
TI  - Epigenetic revival of a dead cardiomyocyte through mitochondrial interventions.
AB  - Mitochondrial dysfunction has been reported to underline heart failure, and our
      earlier report suggests that mitochondrial fusion and fission contributes
      significantly to volume overload heart failure. Although ample studies highlight
      mitochondrial dysfunction to be a major cause, studies are lacking to uncover the
      role of mitochondrial epigenetics, i.e. epigenetic modifications of mtDNA in
      cardiomyocyte function. Additionally, mitochondrial proteases like calpain and
      Lon proteases are underexplored. Cardiomyopathies are correlated to mitochondrial
      damage via increased reactive oxygen species production and free calcium within
      cardiomyocytes. These abnormalities drive increased proteolytic activity from
      matrix metalloproteinases and calpains, respectively. These proteases degrade the
      cytoskeleton of the cardiomyocyte and lead to myocyte death. mtDNA methylation is
      another factor that can lead to myocyte death by silencing several genes of
      mitochondria or upregulating the expression of mitochondrial proteases by
      hypomethylation. Cardiomyocyte resuscitation can occur through mitochondrial
      interventions by decreasing the proteolytic activity and reverting back the
      epigenetic changes in the mtDNA which lead to myocyte dysfunction. Epigenetic
      changes in the mtDNA are triggered by environmental factors like pollution and
      eating habits with cigarette smoking. An analysis of mitochondrial epigenetics in
      cigarette-smoking mothers will reveal an underlying novel mechanism leading to
      mitochondrial dysfunction and eventually heart failure. This review is focused on
      the mitochondrial dysfunction mechanisms that can be reverted back to resuscitate
      cardiomyocytes. 

PMID- 26203603
TI  - Defense peptides: recent developments.
AB  - Defense peptides are small amphipathic molecules that exhibit antimicrobial,
      antitumor, antiviral, and immunomodulatory properties. This review summarizes
      current knowledge on the mechanisms of antimicrobial activity of cationic and
      anionic defense peptides, indicating peptide-based as well as microbial cell
      based factors affecting this activity. The peptide-based factors include charge,
      hydrophibicity, and amphipathicity, whereas the pathogen-based factors are
      membrane lipid composition, presence of sterols, membrane fluidity, cell wall
      components, and secreted factors such as extracellular proteinases. Since defense
      peptides have been considered very promising molecules that could replace
      conventional antibiotics in the era of drug-resistant pathogens, the issue of
      microbial resistance to antimicrobial peptides (AMPs) is addressed. Furthermore,
      selected approaches employed for optimization and de novo design of effective
      AMPs based on the properties recognized as important for the function of natural
      defense peptides are presented. 

PMID- 26203604
TI  - Chest computed tomography for phenotying chronic obstructive pulmonary disease. A
      pathway and a challenge for personalized medicine.

PMID- 26203605
TI  - United airway diseases. Should we add upper airway inflammatory disorders to the
      list of chronic obstructive pulmonary disease comorbidities?

PMID- 26203607
TI  - Small, nonfatal pulmonary emboli. is computed tomographic pulmonary angiography
      the culprit?

PMID- 26203606
TI  - Queens beat one-eyed jacks, but nobody's played the ace yet. Adipokines as
      chronic obstructive pulmonary disease biomarkers.

PMID- 26203608
TI  - The utility of utility scores.

PMID- 26203609
TI  - Managing dyspnea in advanced chronic obstructive pulmonary disease: balancing all
      the evidence.

PMID- 26203610
TI  - Worth a second look. A 49-year-old woman with progressive dyspnea.

PMID- 26203611
TI  - Casting a shadow. A 13-year-old girl with acute chest syndrome and respiratory
      failure.

PMID- 26203612
TI  - Blood and volume resuscitation for variceal hemorrhage.

PMID- 26203613
TI  - Bronchial injury post-cryoablation for atrial fibrillation.

PMID- 26203614
TI  - Spontaneous hemothorax resulting from tissue plasminogen activator in a patient
      with ischemic stroke and unrecognized recent myocardial infarction.

PMID- 26203615
TI  - Benign multicystic mesothelioma causing bilateral pneumothoraces.

PMID- 26203616
TI  - Lansoprazole worsens asthma control in poor metabolizers: is nitric oxide
      involved?

PMID- 26203617
TI  - Reply: worsening asthma control in children taking lansoprazole: possible
      mechanisms.

PMID- 26203618
TI  - FEV1 can be associated with reduced values after vigorous exercise in healthy
      adolescents.

PMID- 26203619
TI  - Reply: FEV1 can be associated with reduced values after vigorous exercise in
      healthy adolescents.

PMID- 26203620
TI  - Erratum: reduced bone density and vertebral fractures in smokers. men and COPD
      patients at increased risk.

PMID- 26203622
TI  - Pediatric Out-of-Hospital Critical Procedures in the United States.
AB  - OBJECTIVE: Regular clinical application is important for maintenance of difficult
      resuscitation skills. Although emergency medical services must provide life
      saving care for critically ill and injured children, the frequency with which
      these procedures are performed is unknown. We sought to characterize critical
      pediatric procedures performed by emergency medical service personnel in the
      United States. DESIGN: We performed a retrospective, descriptive study of
      emergency medical service responses. SETTING AND PATIENTS: We included patients
      less than 18 years old in the 2011 National Emergency Medical Services
      Information Systems national data set. We identified emergency medical service
      cases receiving critical procedures, including intubation, cricothyroidotomy,
      cardiac pacing, cardioversion, defibrillation, needle decompression,
      pericardiocentesis, and intraosseous or central venous catheter placement.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed the data to
      determine the number and prevalence of procedures, success rates, and factors
      associated with success. Of the 14,371,941 emergency medical service responses,
      865,591 (6.8%) involved children. Emergency medical service responses to
      pediatric patients most often involved traumatic injuries (35.7%) or respiratory
      complications (13.2%). Emergency medical service performed a total of 616,913
      procedures on 246,016 pediatric cases. Critical procedures were infrequently
      performed (n = 11,026, 10 per 1,000 pediatric cases). The most common critical
      procedures performed were intubation (n = 3,599, 6.7 per 1,000 pediatric cases)
      and intraosseous access (n = 2,618, 5 per 1,000 pediatric cases). Overall, 81% of
      critical procedures were successful. Increasing age and interfacility transfers
      were associated with greater odds of procedural success (p < 0.01). CONCLUSION:
      Despite the broad range of pediatric conditions seen in the prehospital setting,
      pediatric critical procedures are infrequently performed. These data highlight
      factors that are associated with successful completion of critical pediatric
      procedures.

PMID- 26203621
TI  - An official American Thoracic Society Workshop Report: presentations and
      discussion of the fifth Jack Pepys Workshop on Asthma in the Workplace.
      Comparisons between asthma in the workplace and non-work-related asthma.
AB  - The fifth Jack Pepys Workshop on Asthma in the Workplace focused on the
      similarities and differences of work-related asthma (WRA) and non-work-related
      asthma (non-WRA). WRA includes occupational asthma (OA) and work-exacerbated
      asthma (WEA). There are few biological differences in the mechanisms of
      sensitization to environmental and occupational allergens. Non-WRA and OA, when
      due to high-molecular-weight agents, are both IgE mediated; it is uncertain
      whether OA due to low-molecular-weight agents is also IgE mediated. Risk factors
      for OA include female sex, a history of upper airway symptoms, and a history of
      bronchial hyperresponsiveness. Atopy is a risk factor for OA due to high
      molecular-weight agents, and exposure to cleaning agents is a risk factor for
      both OA and non-WRA. WEA is important among workers with preexisting asthma and
      may overlap with irritant-induced asthma, a type of OA. Induced sputum cytology
      can confirm airway inflammation, but specific inhalation challenge is the
      reference standard diagnostic test. Inhalation challenges are relatively safe,
      with the most severe reactions occurring with low-molecular-weight agents.
      Indirect health care costs account for about 50% of total asthma costs. Workers
      with poor asthma control (WRA or non-WRA) are less likely to be employed. Income
      loss is a major contributor to the indirect costs of WRA. Overall, asthma
      outcomes probably are worse for adult-onset than for childhood-onset asthma but
      better for OA than adult-onset non-WRA. Important aspects of management of OA are
      rapid and proper confirmation of the diagnosis and reduction of exposure to
      sensitizers or irritants at work and home. 

PMID- 26203623
TI  - Stimulant Toxicity in Children: A Retrospective Study on 147 Patients.
AB  - OBJECTIVE: To evaluate the signs/symptoms of different stimulant toxicities in
      children to determine differences among them. DESIGN: Observational,
      retrospective, single-center case-series. SETTING: The only referral hospital for
      pediatric poisoned patients in Tehran, Iran, covering 12.5 million permanent and
      6.5 million temporary residents. PATIENTS: All children between 2007 and 2012
      were evaluated. Their clinical findings, laboratory tests, electrocardiogram, and
      outcome were evaluated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A
      total of 147 patients were enrolled (115, 24, three, and five with
      methamphetamine, methylphenidate, ecstasy, and unknown stimulant toxicities,
      respectively). Median (interquartile range) age of the methamphetamine-
      intoxicated children (16 mo [22-42 mo]) was significantly less than those with
      methylphenidate toxicity (66 mo [33-105 mo]). Almost 79% of the patients had
      ingested the stimulant, whereas 9% had passively been exposed to the
      methamphetamine smoke. The frequency of stimulant toxicity had significantly
      increased during the 5-year period of the study. Restlessness, mydriasis,
      stereotypic movements, and talkativeness were the most common signs and symptoms.
      Whereas bruxism only seen in 66.7% (95% CI, 21-94%) of ecstasy users, the
      prevalence of restlessness, sweating, and tremor was also more in this group of
      children. On the other hand, mydriasis and stereotypic movements were more common
      in crystal-meth patients by 76.5% (95% CI, 68-83%) and 53% (95% CI, 44-62%),
      respectively. A comparison between different routes of crystal-meth intoxication
      showed that flushing was more common in those who had passively/actively
      smoked/inhaled methamphetamine (odds ratio, 6.3 [95% CI, 1.5-26]). Palpitation
      was more seen in methylphenidate toxicity by 12.5% (95% CI, 4-31%). Restlessness
      was more detected in toddlers, whereas talkativeness and ataxia were more common
      in older children. Nineteen children (21%) had prolonged QTc according to normal
      values in different ages. None of them died. CONCLUSIONS: More studies are
      warranted to evaluate the frequency and outcome of this poisoning in children.
      Educational preventive programs are also recommended.

PMID- 26203624
TI  - Fluid Bolus Therapy-Based Resuscitation for Severe Sepsis in Hospitalized
      Children: A Systematic Review.
AB  - OBJECTIVES: To review systematically data from randomized and nonrandomized
      studies of fluid bolus therapy in hospitalized children with septic shock. DATA
      SOURCES: Medline, EMBASE, and Cochrane Central Register of Controlled Trials.
      STUDY SELECTION: We searched for randomized controlled studies of fluid bolus
      therapy in children with severe sepsis. We identified retrospective, prospective,
      and observational studies. We excluded studies of severe sepsis/septic shock due
      to a specific microbiological etiology, neonatal studies, and studies where
      advanced supportive therapies were unavailable. DATA EXTRACTION: Two authors
      screened articles for inclusion. DATA SYNTHESIS: We identified and analyzed three
      randomized controlled trials and eight nonrandomized studies. Heterogeneity
      precluded meta-analysis. Two single-center Indian studies and one Brazilian study
      assessed three different fluid bolus therapy regimens in small cohorts with
      different populations, physiological triggers, and physiological and clinical
      outcomes. No randomized controlled trials compared fluid bolus therapy with
      alternative interventions, such as vasopressors. The nonrandomized studies were
      heterogeneous in populations, methodology, and outcome measures. No observed
      physiological differences were identified based on volume of fluid bolus therapy.
      CONCLUSIONS: There are only limited data to support the use of fluid bolus
      therapy in hospitalized children. Prospective observational data and randomized
      controlled trials are urgently needed to evaluate this therapy in resource rich
      settings.

PMID- 26203625
TI  - Measuring Blood Flow: So What?

PMID- 26203626
TI  - A Data-Driven Evolutionary Algorithm for Mapping Multibasin Protein Energy
      Landscapes.
AB  - Evidence is emerging that many proteins involved in proteinopathies are dynamic
      molecules switching between stable and semistable structures to modulate their
      function. A detailed understanding of the relationship between structure and
      function in such molecules demands a comprehensive characterization of their
      conformation space. Currently, only stochastic optimization methods are capable
      of exploring conformation spaces to obtain sample-based representations of
      associated energy surfaces. These methods have to address the fundamental but
      challenging issue of balancing computational resources between exploration
      (obtaining a broad view of the space) and exploitation (going deep in the energy
      surface). We propose a novel algorithm that strikes an effective balance by
      employing concepts from evolutionary computation. The algorithm leverages
      deposited crystal structures of wildtype and variant sequences of a protein to
      define a reduced, low-dimensional search space from where to rapidly draw
      samples. A multiscale technique maps samples to local minima of the all-atom
      energy surface of a protein under investigation. Several novel algorithmic
      strategies are employed to avoid premature convergence to particular minima and
      obtain a broad view of a possibly multibasin energy surface. Analysis of
      applications on different proteins demonstrates the broad utility of the
      algorithm to map multibasin energy landscapes and advance modeling of multibasin
      proteins. In particular, applications on wildtype and variant sequences of
      proteins involved in proteinopathies demonstrate that the algorithm makes an
      important first step toward understanding the impact of sequence mutations on
      misfunction by providing the energy landscape as the intermediate explanatory
      link between protein sequence and function. 

PMID- 26203627
TI  - Engineering high-performance Pd core-MgO porous shell nanocatalysts via
      heterogeneous gas-phase synthesis.
AB  - We report on the design and synthesis of high performance catalytic nanoparticles
      with a robust geometry via magnetron-sputter inert-gas condensation. Sputtering
      of Pd and Mg from two independent neighbouring targets enabled heterogeneous
      condensation and growth of nanoparticles with controlled Pd core-MgO porous shell
      structure. The thickness of the shell and the number of cores within each
      nanoparticle could be tailored by adjusting the respective sputtering powers. The
      nanoparticles were directly deposited on glassy carbon electrodes, and their
      catalytic activity towards methanol oxidation was examined by cyclic voltammetry.
      The measurements indicated that the catalytic activity was superior to
      conventional bare Pd nanoparticles. As confirmed by electron microscopy imaging
      and supported by density-functional theory (DFT) calculations, we attribute the
      improved catalytic performance primarily to inhibition of Pd core sintering
      during the catalytic process by the metal-oxide shell. 

PMID- 26203628
TI  - Launch of a Nationwide Hepatitis C Elimination Program--Georgia, April 2015.
AB  - Hepatitis C virus (HCV) infects an estimated 130-150 million persons globally and
      results in an estimated 700,000 deaths annually from hepatocellular carcinoma or
      cirrhosis. Georgia, a middle-income Eurasian country, has one of the highest
      estimated HCV prevalences in the world. In 2011, Georgia began offering treatment
      to a limited number of HCV-infected persons. Beginning in 2013, when new oral
      medications that can cure >90% of HCV infections were licensed, Georgia engaged
      partners to develop a comprehensive HCV prevention and control plan, during which
      the concept of elimination of HCV transmission and disease emerged. To prepare
      for the launch of an HCV elimination program, Georgia requested CDC's assistance
      to describe HCV epidemiology, evaluate laboratory and health care capacity, and
      conduct program monitoring and evaluation. This report describes the activities
      undertaken to prepare for the program, launched in April 2015, and early results
      of its initial phase, focused on improving access to affordable diagnostics and
      free curative treatment for HCV-infected persons with severe liver disease. A
      national population-based serosurvey began in May 2015, and four clinical sites
      and their laboratories were selected as initial pilot sites; since June, three
      additional sites have been added. Through July 3, 2015, a total of 6,491 persons
      sought treatment, and 6,177 (95.2%) initiated diagnostic work-up. Among these,
      1,519 (24.6%) completed work-up, 1,474 (97.0%) of whom initiated treatment.
      Georgia is scaling up capacity to meet the demand for HCV treatment and is
      collaborating with CDC and other partners on development of a comprehensive HCV
      elimination plan that includes specific goals and activities needed to achieve
      them. 

PMID- 26203629
TI  - Viral Hepatitis Surveillance--India, 2011-2013.
AB  - The burden of viral hepatitis in India is not well characterized. In 2009, the
      national Integrated Disease Surveillance Programme (IDSP) began conducting
      surveillance across all Indian states for epidemic-prone diseases, including
      foodborne and waterborne forms of viral hepatitis (e.g., hepatitis A and E).
      Information on outbreaks of all forms of viral hepatitis, including A, B, C, and
      E, also is collected. This report summarizes viral hepatitis surveillance and
      outbreak data reported to IDSP during 2011-2013. During this period, 804,782
      hepatitis cases and 291 outbreaks were reported; the virus type was unspecified
      in 92% of cases. Among 599,605 cases tested for hepatitis A, 44,663 (7.4%) were
      positive, and among 187,040 tested for hepatitis E, 19,508 (10.4%) were positive.
      At least one hepatitis outbreak report was received from 23 (66%) of 35 Indian
      states. Two-thirds of outbreaks were reported from rural areas. Among 163 (56%)
      outbreaks with known etiology, 78 (48%) were caused by hepatitis E, 54 (33%) by
      hepatitis A, 19 (12%) by both hepatitis A and E, and 12 (7%) by hepatitis B or
      hepatitis C. Contaminated drinking water was the source of most outbreaks.
      Improvements in water quality and sanitation as well as inclusion of hepatitis A
      vaccine in childhood immunization programs should be considered to reduce the
      public health burden of hepatitis in India. Efforts to decrease the proportion of
      cases for which the etiology is unspecified, including expanding the IDSP to
      support hepatitis B and C testing, might help further elucidate the epidemiology
      of these diseases. 

PMID- 26203630
TI  - Severe Illness from Methyl Bromide Exposure at a Condominium Resort--U.S. Virgin
      Islands, March 2015.
AB  - On March 22, 2015, the Agency for Toxic Substances and Disease Registry (ATSDR)
      was notified by the U.S. Environmental Protection Agency (EPA) of four cases of
      suspected acute methyl bromide toxicity among family members vacationing at a
      condominium resort in the U.S. Virgin Islands. Methyl bromide is a pesticide that
      has been banned in the United States for use in homes and other residential
      settings. An investigation conducted by the U.S. Virgin Islands Department of
      Health (VIDOH), the U.S. Virgin Islands Department of Planning and Natural
      Resources (DPNR), and EPA confirmed that methyl bromide had been used as a
      fumigant on March 18 in the building where the family had been residing, 2 days
      before they were transported to the hospital; three family members had life
      threatening illness. On March 25, 2015, a stop-use order for methyl bromide was
      issued by DPNR to the pest control company that had performed the fumigation.
      Subsequent investigation revealed that previous fumigation with methyl bromide
      had occurred on October 20, 2014, at the same condominium resort. In addition to
      the four ill family members, 37 persons who might have been exposed to methyl
      bromide as a result of the October 2014 or March 2015 fumigations were identified
      by VIDOH and ATSDR. Standardized health questionnaires were administered to 16 of
      the 20 persons for whom contact information was available; six of 16 had symptoms
      consistent with methyl bromide exposure, including headache and fatigue. Pest
      control companies should be aware that use of methyl bromide is banned in homes
      and other residential settings, and clinicians should be aware of the toxicologic
      syndrome that exposure to methyl bromide can cause. 

PMID- 26203631
TI  - Knowledge and Attitudes Regarding Antibiotic Use Among Adult Consumers, Adult
      Hispanic Consumers, and Health Care Providers--United States, 2012-2013.
AB  - Appropriate antibiotic use, in particular avoidance of antibiotics for upper
      respiratory infections likely to be caused by viruses, is a key component of
      efforts to slow the increase in antibiotic-resistant infections. Studies suggest
      that Hispanic consumers might differ from non-Hispanic consumers in their
      knowledge and attitudes regarding antibiotic use (4). To better understand health
      care provider and consumer knowledge and attitudes that influence antibiotic use,
      CDC analyzed national internet survey data collected from participants living in
      the United States during 2012-2013. The participants represented three groups: 1)
      the total population of adult consumers (all ethnicities); 2) adult Hispanic
      consumers; and 3) health care providers. Hispanic consumers were more likely than
      all consumers to believe that if they have a cold, antibiotics would help them to
      get better more quickly (48% versus 25%), and more likely to obtain antibiotics
      not prescribed by a clinician, such as antibiotics left over from a previous
      illness (25% versus 9%), obtained from a neighborhood grocery store (23% versus
      5%), or obtained from a friend or family member (17% versus 6%). Most providers
      surveyed (54%) reported that they believed their patients expect antibiotics
      during visits for a cough or cold, whereas 26% of all consumers reported this
      expectation. To maximize knowledge about appropriate antibiotic use among
      outpatients in the United States, public health initiatives should target
      Hispanic as well as general audiences. 

PMID- 26203632
TI  - Notes from the Field: Death Following Ingestion of an Edible Marijuana Product-
      Colorado, March 2014.
AB  - In March 2014, the Colorado Department of Public Health and Environment (CDPHE)
      learned of the death of a man aged 19 years after consuming an edible marijuana
      product. CDPHE reviewed autopsy and police reports to assess factors associated
      with his death and to guide prevention efforts. The decedent's friend, aged 23
      years, had purchased marijuana cookies and provided one to the decedent. A police
      report indicated that initially the decedent ate only a single piece of his
      cookie, as directed by the sales clerk. Approximately 30-60 minutes later, not
      feeling any effects, he consumed the remainder of the cookie. During the next 2
      hours, he reportedly exhibited erratic speech and hostile behaviors.
      Approximately 3.5 hours after initial ingestion, and 2.5 hours after consuming
      the remainder of the cookie, he jumped off a fourth floor balcony and died from
      trauma. The autopsy, performed 29 hours after time of death, found marijuana
      intoxication as a chief contributing factor. Quantitative toxicologic analyses
      for drugs of abuse, synthetic cannabinoid, and cathinones ("bath salts") were
      performed on chest cavity blood by gas chromatography and mass spectrometry. The
      only confirmed findings were cannabinoids (7.2 ng/mL delta-9 tetrahydrocannabinol
      [THC] and 49 ng/mL delta-9 carboxy-THC, an inactive marijuana metabolite). The
      legal whole blood limit of delta-9 THC for driving a vehicle in Colorado is 5.0
      ng/mL. This was the first reported death in Colorado linked to marijuana
      consumption without evidence of polysubstance use since the state approved
      recreational use of marijuana in 2012. 

PMID- 26203633
TI  - Notes from the Field: Outbreak of Cryptosporidiosis Among Veterinary Medicine
      Students--Philadelphia, Pennsylvania, February 2015.
AB  - On February 20, 2015, a northeastern university's student health center was
      notified of five veterinary medicine students with gastrointestinal symptoms. An
      investigation was conducted to establish the existence of an outbreak, determine
      the etiology, evaluate risk factors, and recommend control measures. 

PMID- 26203634
TI  - Microencapsulated sorbic acid and pure botanicals affect Salmonella Typhimurium
      shedding in pigs: a close-up look from weaning to slaughter in controlled and
      field conditions.
AB  - The aim of this study was to assess the efficacy of a combination of sorbic acid,
      thymol, and carvacrol in reducing the prevalence and shedding level of Salmonella
      Typhimurium in pigs either in a controlled challenge environment or in a
      production setting. In the first study, 24 weaned piglets were separated in 4
      isolation units (6 piglets/isolation unit). Each unit received either a basal
      diet (no treatment) or a microencapsulated mixture of sorbic acid, thymol, and
      carvacrol at 1, 2, or 5 g/kg of feed. After 21 d, pigs were orally challenged
      with 6 log10 colony-forming units of Salmonella Typhimurium. Blood samples and
      feces from rectal ampullae were collected every week. On d56 of the study, pigs
      were euthanized and necropsied to collect intestinal contents (jejunum through
      colon) and ileocecal lymph nodes. Samples were analyzed for Salmonella
      Typhimurium and serological analysis was also conducted. In the second study, an
      all-in-all-out multisite pig farm that was positive for monophasic Salmonella
      Typhimurium was followed throughout a production cycle from weaning to slaughter.
      Pigs received either a basal diet or the basal diet including 5 g/kg of the
      microencapsulated additive. Environmental, fecal, and blood samples were
      collected monthly, and cecal contents and ileocecal lymph nodes were collected at
      slaughter to isolate and enumerate Salmonella. The results indicate that the
      additive at 5 g/kg tended to reduce Salmonella fecal prevalence in both a
      controlled challenge (p=0.07) and in production conditions (p=0.03).
      Nevertheless, the additive did not reduce the number of pigs seropositive for
      Salmonella, nor it reduced the Salmonella prevalence at slaughter. The data
      indicate that these additives are not effective alone but must be used in
      conjunction with appropriate containment measures at lairage in order to prevent
      reinfection in pigs and to reduce the number of pigs carrying Salmonella entering
      the food chain. 

PMID- 26203635
TI  - Nazarov cyclization of dienylaziridines: synthesis of
      cyclopentadienyl/hydrinedienyl/indenyl glycines.
AB  - Cyclopentadienyl, hydrinedienyl, and indenyl glycines were synthesized using
      dienylaziridines as Nazarov cyclization precursors for the first time. Several
      substrates were synthesized to demonstrate the compatibility of this reaction.
      Asymmetric synthesis of these amino acids was also developed to show the
      additional scope of this method. 

PMID- 26203636
TI  - Unprocessed Interleukin-36alpha Regulates Psoriasis-Like Skin Inflammation in
      Cooperation With Interleukin-1.
AB  - Generalized pustular psoriasis is a severe skin disease characterized by
      epidermal hyperplasia, neutrophil-rich abscesses within the epidermis, and a
      mixed inflammatory infiltrate in the dermis. The disease may be caused by
      missense mutations in the IL-36 receptor antagonist, IL-36Ra. Curiously, the
      related IL-1Ra has therapeutic effects in some of these latter patients. Here,
      using an experimental mouse model of psoriasiform skin inflammation, we
      demonstrate in vivo connections between IL-36 and IL-1 expression. After disease
      initiation, IL-36alpha-deficient mice exhibited dramatically diminished skin
      pathology, including absence of epidermal neutrophils, reduced keratinocyte
      acanthosis, and less dermal edema. In contrast, IL-36beta and IL-36gamma knockout
      mice developed disease indistinguishable from that of wild-type mice. The
      endogenous IL-36alpha was not processed through proteolysis. Although IL-36alpha
      expression was strongly induced in an IL-1 signaling-dependent manner during
      disease, expression of IL-1alpha was also dependent upon IL-36alpha. Hence, after
      being upregulated by IL-1alpha, IL-36alpha acts through a feedback mechanism to
      boost IL-1alpha levels. Analyses of double knockout mice further revealed that IL
      36alpha and IL-1alpha cooperate to promote psoriasis-like disease. In conclusion,
      IL-1alpha and IL-36alpha form a self-amplifying inflammatory loop in vivo that in
      patients with insufficient counter regulatory mechanisms may become hyper-engaged
      and/or chronic. 

PMID- 26203637
TI  - Integrin alphaE(CD103) Is Involved in Regulatory T-Cell Function in Allergic
      Contact Hypersensitivity.
AB  - Murine contact hypersensitivity (CHS) is a dendritic cell (DC)-dependent T-cell
      mediated inflammation with CD8+ T cells as effectors and CD4+ T cells as
      regulators (Treg cells) that models human allergic contact dermatitis. The
      integrin alphaE(CD103) is expressed by some T-cell and DC subsets and has been
      implicated in epithelial lymphocyte localization, but its role in immune
      regulation remains enigmatic. We have identified a function for CD103 in the
      development of cutaneous allergic immune responses. CHS responses, but not
      irritant contact dermatitis, were significantly augmented in CD103-deficient mice
      in hapten-challenged skin. Phenotype and function of skin DCs during
      sensitization were normal, whereas adoptive transfer experiments revealed that
      the elevated CHS response in CD103-deficient mice is transferred by primed T
      cells and is independent of resident cells in recipient mice. While T-cell counts
      were elevated in challenged skin of CD103-deficient mice, the FoxP3 expression
      level of CD4+CD25+ Treg cells was significantly reduced, indicating impaired
      functionality. Indeed, Treg cells from CD103-deficient mice were not able to
      suppress CHS reactions during the elicitation phase. Further, CD103 on FoxP3+
      Treg cells was involved in Treg retention to inflamed skin. These findings
      indicate an unexpected dichotomous functional role for CD103 on Treg cells by
      modulating FoxP3 expression.

PMID- 26203638
TI  - Invasion of Herpes Simplex Virus Type 1 into Murine Epidermis: An Ex Vivo
      Infection Study.
AB  - Herpes simplex virus type 1 (HSV-1) invades its human host via the skin or
      mucosa. We aim to understand how HSV-1 overcomes the barrier function of the host
      epithelia, and for this reason, we established an ex vivo infection assay
      initially with murine skin samples. Here, we report how tissue has to be prepared
      to be susceptible to HSV-1 infection. Most efficient infection of the epidermis
      was achieved by removing the dermis. HSV-1 initially invaded the basal epidermal
      layer, and from there, spreading to the suprabasal layers was observed.
      Strikingly, in resting stage hair follicles, only the hair germ was infected,
      whereas the quiescent bulge stem cells (SCs) were resistant to infection.
      However, during the growth phase, infected cells were also detected in the
      activated bulge SCs. We demonstrated that cell proliferation was not a
      precondition for HSV-1 invasion, but SC activation was required as shown by
      infection of aberrantly activated bulge SCs in integrin-linked kinase (ILK)
      deficient hair follicles. These results suggest that the status of the bulge SCs
      determines whether HSV-1 can reach its receptors, whereas the receptors on basal
      keratinocytes are accessible irrespective of their proliferation status. 

PMID- 26203639
TI  - Intravenously Administered Recombinant Human Type VII Collagen Derived from
      Chinese Hamster Ovary Cells Reverses the Disease Phenotype in Recessive
      Dystrophic Epidermolysis Bullosa Mice.
AB  - Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited disorder
      characterized by skin fragility, blistering, and multiple skin wounds with no
      currently approved or consistently effective treatment. It is due to mutations in
      the gene encoding type VII collagen (C7). Using recombinant human C7 (rhC7)
      purified from human dermal fibroblasts (FB-rhC7), we showed previously that
      intravenously injected rhC7 distributed to engrafted RDEB skin, incorporated into
      its dermal-epidermal junction (DEJ), and reversed the RDEB disease phenotype.
      Human dermal fibroblasts, however, are not used for commercial production of
      therapeutic proteins. Therefore, we generated rhC7 from Chinese hamster ovary
      (CHO) cells. The CHO-derived recombinant type VII collagen (CHO-rhC7), similar to
      FB-rhC7, was secreted as a correctly folded, disulfide-bonded, helical trimer
      resistant to protease degradation. CHO-rhC7 bound to fibronectin and promoted
      human keratinocyte migration in vitro. A single dose of CHO-rhC7, administered
      intravenously into new-born C7-null RDEB mice, incorporated into the DEJ of
      multiple skin sites, tongue and esophagus, restored anchoring fibrils, improved
      dermal-epidermal adherence, and increased the animals' life span. Furthermore, no
      circulating or tissue-bound anti-C7 antibodies were observed in the mice. These
      data demonstrate the efficacy of CHO-rhC7 in a preclinical murine model of RDEB. 

PMID- 26203640
TI  - SASH1 Is Involved in an Autosomal Dominant Lentiginous Phenotype.

PMID- 26203642
TI  - Treatment Decision Making and Genetic Testing for Breast Cancer: Mainstreaming
      Mutations.

PMID- 26203641
TI  - Activating CARD14 Mutations Are Associated with Generalized Pustular Psoriasis
      but Rarely Account for Familial Recurrence in Psoriasis Vulgaris.
AB  - Caspase recruitment family member 14 (CARD14, also known as CARMA2), is a
      scaffold protein that mediates NF-kappaB signal transduction in skin
      keratinocytes. Gain-of-function CARD14 mutations have been documented in familial
      forms of psoriasis vulgaris (PV) and pityriasis rubra pilaris (PRP). More recent
      investigations have also implicated CARD14 in the pathogenesis of pustular
      psoriasis. Follow-up studies, however, have been limited, so that it is not clear
      to what extent CARD14 alleles account for the above conditions. Here, we sought
      to address this question by carrying out a systematic CARD14 analysis in an
      extended patient cohort (n=416). We observed no disease alleles in subjects with
      familial PV (n=159), erythrodermic psoriasis (n=23), acral pustular psoriasis
      (n=100), or sporadic PRP (n=29). Conversely, our analysis of 105 individuals with
      generalized pustular psoriasis (GPP) identified a low-frequency variant
      (p.Asp176His) that causes constitutive CARD14 oligomerization and shows a
      significant association with GPP in Asian populations (P=8.4*10(-5); odds
      ratio=6.4). These data indicate that the analysis of CARD14 mutations could help
      stratify pustular psoriasis cohorts but would be mostly uninformative in the
      context of psoriasis and sporadic PRP.

PMID- 26203643
TI  - Addition of Suprascapular Nerve Block to a Physical Therapy Program Produces an
      Extra Benefit to Adhesive Capsulitis: A Randomized Controlled Trial.
AB  - OBJECTIVE: The aim of this study was to compare the efficacy of suprascapular
      nerve block plus physical therapy (PT) with PT alone for the treatment of
      adhesive capsulitis of the shoulder. DESIGN: Forty-one patients with adhesive
      capsulitis were randomly assigned to the injection group (n = 19) or PT-alone
      control group (n = 22). All patients received PT consisting of electrotherapy,
      range of motion, stretching, and strengthening exercises. The patients in the
      injection group received suprascapular nerve block before PT. Pain was assessed
      using the Brief Pain Inventory-Short Form, and functional status was assessed
      with the total Constant score. RESULTS: In both groups, significant differences
      were found in all parameters of the Brief Pain Inventory-Short Form compared with
      baseline levels apart from walking ability in the last 24 hrs (P = not
      applicable). However, the differences of mean pain severity in the last 24 hrs at
      first to second and first to third assessments, pain severity at that time at
      first to second assessments, percentage improvement at second to third
      assessments, general activity in the last 24 hrs at first to second and first to
      third assessments, and enjoyment of life in the last 24 hrs at first to second
      and first to third assessments were statistically significant in favor of the
      injection group (P < 0.05). CONCLUSIONS: The current study supports that
      suprascapular nerve block is a safe and well-tolerated method. PT was found to be
      effective in reducing pain severity and functional disability, and the addition
      of suprascapular nerve block to PT improved functional status and pain levels in
      patients with adhesive capsulitis.

PMID- 26203644
TI  - Bilateral Homonymous Quadrantanopsia due to Optic Radiation Injury in a Patient
      with Traumatic Brain Injury.

PMID- 26203646
TI  - Comment on: Functional Outcomes of Patients with Amputation Receiving Chronic
      Dialysis for End-Stage Renal Disease.

PMID- 26203647
TI  - Structure and optoelectronic properties of helical pyridine-furan, pyridine
      pyrrole and pyridine-thiophene oligomers.
AB  - Density functional theory based calculations have been carried out to
      systematically investigate the structural and optoelectronic properties of
      pyridine-furan, pyridine-pyrrole and pyridine-thiophene oligomers. Comparison of
      results obtained at B3LYP/6-31G(d) and B3LYP-D3/6-31G(d) levels of theories
      reveals that the inclusion of dispersion correction with the B3LYP functional has
      a major impact on ground state structures and stabilities of the most stable
      conformers, which are helical for our studied systems. Calculation of
      stabilization energies, gained due to non-bonding interaction between adjacent
      helical turns, shows that stabilities of helical oligomers increase with an
      increase in the chain length. Ground state dipole moment values of these helical
      oligomers fluctuate between a certain range and these values depend on the number
      of repeating units (n) and the number of repeating units needed to complete one
      helical turn (u) of a helix. To obtain vertical excitation energies, oscillator
      strengths and absorption spectra of each oligomer, time dependent density
      functional theory single point calculations were carried out at the B3LYP-D3/6
      31G(d) level using optimized geometries obtained at the same level. The
      absorption spectrum of a helical oligomer is composed of multiple electronic
      transitions having significant oscillator strengths and the transition with the
      largest oscillator strength is blue shifted with an increase in the size of the
      oligomer. Furthermore, for the most important electronic transition (S0-> Sm) of
      oligomers with n > u, m increases with increasing n. For these helices,
      excitations involving molecular orbitals other than frontier molecular orbitals
      significantly contribute to major electronic transitions. 

PMID- 26203645
TI  - Clinical Efficacy of Mudpack Therapy in Treating Knee Osteoarthritis: A Meta
      Analysis of Randomized Controlled Studies.
AB  - OBJECTIVE: The objective of this study was to evaluate the clinical efficacy of
      mudpack therapy for the treatment of knee osteoarthritis and identify the likely
      factors associated with the high heterogeneity of combined studies. DESIGN: The
      Medline, Embase, and Cochrane Library databases were systematically searched for
      randomized controlled trials in which mudpack therapy was used to treat knee
      osteoarthritis. RESULTS: Ten publications that reported the results from a total
      of 1010 subjects were included in this meta-analysis. Meta-analysis of
      improvement in joint function at the final follow-up visit suggested, given that
      the follow-up time was less than 4 mos, that the combined effect size of four
      studies was -0.30 (-0.62 to 0.02) and the difference did not reach the level of
      statistical significance. When the follow-up time reached 4 mos, the combined
      effect size was -1.10 (-2.07 to -0.14) and the difference was significant. The I
      values of the two groups were 21.4% and 93.8%. CONCLUSION: Functional improvement
      of the knee joint in patients treated with mudpack therapy was not significantly
      different from that of control subjects at the end of the 4-mo follow-up. The
      quality of current publications was a factor causing heterogeneity.

PMID- 26203648
TI  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interacts with
      apurinic/apyrimidinic sites in DNA.
AB  - Apurinic/apyrimidinic (AP) sites are some of the most frequent DNA damages and
      the key intermediates of base excision repair. Certain proteins can interact with
      the deoxyribose of the AP site to form a Schiff base, which can be stabilized by
      NaBH4 treatment. Several types of DNA containing the AP site were used to trap
      proteins in human cell extracts by this method. In the case of single-stranded AP
      DNA and AP DNA duplex with both 5' and 3' dangling ends, the major crosslinking
      product had an apparent molecular mass of 45 kDa. Using peptide mass mapping
      based on mass spectrometry data, we identified the protein forming this adduct as
      an isoform of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) called "uracil-DNA
      glycosylase". GAPDH is a glycolytic enzyme with many additional putative
      functions, which include interaction with nucleic acids, different DNA damages
      and DNA repair enzymes. We investigated interaction of GAPDH purified from HeLa
      cells and rabbit muscles with different AP DNAs. In spite of the ability to form
      a Schiff-base intermediate with the deoxyribose of the AP site, GAPDH does not
      display the AP lyase activity. In addition, along with the borohydride-dependent
      adducts with AP DNAs containing single-stranded regions, GAPDH was also shown to
      form the stable borohydride-independent crosslinks with these AP DNAs. GAPDH was
      proven to crosslink preferentially to AP DNAs cleaved via the beta-elimination
      mechanism (spontaneously or by AP lyases) as compared to DNAs containing the
      intact AP site. The level of GAPDH-AP DNA adduct formation depends on oxidation
      of the protein SH-groups; disulfide bond reduction in GAPDH leads to the loss of
      its ability to form the adducts with AP DNA. A possible role of formation of the
      stable adducts with AP sites by GAPDH is discussed.

PMID- 26203649
TI  - Kinetic analysis of bypass of abasic site by the catalytic core of yeast DNA
      polymerase eta.
AB  - Abasic sites (Apurinic/apyrimidinic (AP) sites), produced ~ 50,000
      times/cell/day, are very blocking and miscoding. To better understand miscoding
      mechanisms of abasic site for yeast DNA polymerase eta, pre-steady-state
      nucleotide incorporation and LC-MS/MS sequence analysis of extension product were
      studied using pol eta(core) (catalytic core, residues 1-513), which can
      completely eliminate the potential effects of the C-terminal C2H2 motif of pol
      eta on dNTP incorporation. The extension beyond the abasic site was very
      inefficient. Compared with incorporation of dCTP opposite G, the incorporation
      efficiencies opposite abasic site were greatly reduced according to the order of
      dGTP > dATP >> dCTP and dTTP. Pol eta(core) showed no fast burst phase for any
      incorporation opposite G or abasic site, suggesting that the catalytic step is
      not faster than the dissociation of polymerase from DNA. LC-MS/MS sequence
      analysis of extension products showed that 53% products were dGTP
      misincorporation, 33% were dATP and 14% were -1 frameshift, indicating that Pol
      eta(core) bypasses abasic site by a combined G-rule, A-rule and -1 frameshift
      deletions. Compared with full-length pol eta, pol eta(core) relatively reduced
      the efficiency of incorporation of dCTP opposite G, increased the efficiencies of
      dNTP incorporation opposite abasic site and the exclusive incorporation of dGTP
      opposite abasic site, but inhibited the extension beyond abasic site, and
      increased the priority in extension of A: abasic site relative to G: abasic site.
      This study provides further understanding in the mutation mechanism of abasic
      sites for yeast DNA polymerase eta.

PMID- 26203650
TI  - Regional Extinctions and Quaternary Shifts in the Geographic Range of
      Lestodelphys halli, the Southernmost Living Marsupial: Clues for Its
      Conservation.
AB  - The Patagonian opossum (Lestodelphys halli), the southernmost living marsupial,
      inhabits dry and open environments, mainly in the Patagonian steppe (between ~32 
      degrees S and ~49  degrees S). Its rich fossil record shows its occurrence
      further north in Central Argentina during the Quaternary. The paleoenvironmental
      meaning of the past distribution of L. halli has been mostly addressed in a
      subjective framework without an explicit connection with the climatic "space"
      currently occupied by this animal. Here, we assessed the potential distribution
      of this species and the changes occurred in its geographic range during late
      Pleistocene-Holocene times and linked the results obtained with conservation
      issues. To this end, we generated three potential distribution models with fossil
      records and three with current ones, using MaxEnt software. These models showed a
      decrease in the suitable habitat conditions for the species, highlighting a range
      shift from Central-Eastern to South-Western Argentina. Our results support that
      the presence of L. halli in the Pampean region during the Pleistocene-Holocene
      can be related to precipitation and temperature variables and that its current
      presence in Patagonia is more related to temperature and dominant soils. The
      models obtained suggest that the species has been experiencing a reduction in its
      geographic range since the middle Holocene, a process that is in accordance with
      a general increase in moisture and temperature in Central Argentina. Considering
      the findings of our work and the future scenario of global warming projected for
      Patagonia, we might expect a harsh impact on the distribution range of this
      opossum in the near future.

PMID- 26203651
TI  - Molecular Analysis of Antibiotic Resistance Determinants and Plasmids in
      Malaysian Isolates of Multidrug Resistant Klebsiella pneumoniae.
AB  - Infections caused by multidrug resistant Klebsiella pneumoniae have been
      increasingly reported in many parts of the world. A total of 93 Malaysian
      multidrug resistant K. pneumoniae isolated from patients attending to University
      of Malaya Medical Center, Kuala Lumpur, Malaysia from 2010-2012 were investigated
      for antibiotic resistance determinants including extended-spectrum beta
      lactamases (ESBLs), aminoglycoside and trimethoprim/sulfamethoxazole resistance
      genes and plasmid replicons. CTX-M-15 (91.3%) was the predominant ESBL gene
      detected in this study. aacC2 gene (67.7%) was the most common gene detected in
      aminoglycoside-resistant isolates. Trimethoprim/sulfamethoxazole resistance
      (90.3%) was attributed to the presence of sul1 (53.8%) and dfrA (59.1%) genes in
      the isolates. Multiple plasmid replicons (1-4) were detected in 95.7% of the
      isolates. FIIK was the dominant replicon detected together with 13 other types of
      plasmid replicons. Conjugative plasmids (1-3 plasmids of ~3-100 kb) were obtained
      from 27 of 43 K. pneumoniae isolates. An ESBL gene (either CTX-M-15, CTX-M-3 or
      SHV-12) was detected from each transconjugant. Co-detection with at least one of
      other antibiotic resistance determinants [sul1, dfrA, aacC2, aac(6')-Ib, aac(6')
      Ib-cr and qnrB] was noted in most conjugative plasmids. The transconjugants were
      resistant to multiple antibiotics including beta-lactams, gentamicin and
      cotrimoxazole, but not ciprofloxacin. This is the first study describing the
      characterization of plasmids circulating in Malaysian multidrug resistant K.
      pneumoniae isolates. The results of this study suggest the diffusion of highly
      diverse plasmids with multiple antibiotic resistance determinants among the
      Malaysian isolates. Effective infection control measures and antibiotic
      stewardship programs should be adopted to limit the spread of the multidrug
      resistant bacteria in healthcare settings. 

PMID- 26203652
TI  - Possible Contrast Media Reduction with Low keV Monoenergetic Images in the
      Detection of Focal Liver Lesions: A Dual-Energy CT Animal Study.
AB  - OBJECTIVE: To investigate the feasibility of dual-energy CT for contrast media
      (CM) reduction in the diagnosis of hypervascular and hypovascular focal liver
      lesions (FLL). SUBJECTS AND METHODS: The Institutional Animal Care and Use
      Committee approved this study. VX2 tumors were implanted in two different
      segments of the liver in 13 rabbits. After 2 weeks, two phase contrast enhanced
      CT scans including the arterial phase (AP) and portal-venous phase (PVP) were
      performed three times with 24-hour intervals with three different concentrations
      of iodine, 300 (I(300)), 150 (I(150)) and 75 mg I/mL (I(75)). The mean HU and
      standard deviation (SD) were measured in the liver, the hypervascular portion of
      the VX2 tumor which represented hypervascular tumors, and the central necrotic
      area of the VX2 tumor which represented hypovascular tumors in 140 kVp images
      with I(300) as a reference standard and in monoenergetic images (between 40 keV
      and 140 keV) with I(150) and I(75). The contrast-to-noise ratio (CNR) for FLLs
      and the ratio of the CNRs (CNR(ratio)) between monoenergetic image sets with
      I(150) and I(75), and the reference standard were calculated. RESULTS: For
      hypervascular lesions, the CNR(ratio) was not statistically different from 1.0
      between 40 keV and 70 keV images with I(150), whereas the CNR(ratio) was
      significantly lower than 1.0 in all keV images with I(75). For hypovascular
      lesions, the CNR(ratio) was similar to or higher than 1.0 between 40 keV and 80
      keV with I(150) and between 40 keV and 70 keV with I(75).. CONCLUSIONS: With dual
      energy CT, the total amount of CM might be halved in the diagnosis of
      hypervascular FLLs and reduced to one-fourth in the diagnosis of hypovascular
      FLLs, while still preserving CNRs.

PMID- 26203654
TI  - Ecological Dynamics of Two Distinct Viruses Infecting Marine Eukaryotic
      Decomposer Thraustochytrids (Labyrinthulomycetes, Stramenopiles).
AB  - Thraustochytrids are cosmopolitan osmotrophic or heterotrophic microorganisms
      that are considered as important decomposers in coastal ecosystems. However,
      because of a lack of estimation method for each genus or systematic group of
      them, relatively little is known about their ecology in situ. Previously, we
      reported two distinct types of virus infecting thraustochytrids (AuRNAV: reported
      as SssRNAV, and SmDNAV) suggesting they have wide distributions in the host-virus
      systems of coastal environments. Here we conducted a field survey from 2004
      through 2005 to show the fluctuation pattern of thraustochytrids and their
      viruses in Hiroshima Bay, Japan. During the field survey, we monitored the
      dynamics of the two types of thraustochytrid-infecting virus: small viruses
      causing lysis of Aurantiochytrium sp. NIBH N1-27 (identified as AuRNAV) and the
      large viruses of Sicyoidochytrium minutum NBRC 102975 (similar to SmDNAV in
      physiology and morphology). Fluctuation patterns of the two distinct types of
      virus were different from each other. This may reflect the difference in the
      preference of organic substrates; i.e., it may be likely the host of AuRNAV
      (Aurantiochytrium sp.) increases utilizing algal dead bodies or feeble cells as
      the virus shows a large increase in abundance following raphidophyte blooms;
      whereas, the trophic nutrient supply for S. minutum may primarily depend on other
      constantly-supplied organic compounds because it did not show any significant
      change in abundance throughout the survey. Further study concerning the
      population composition of thraustochytrids and their viruses may demonstrate the
      microbial ecology (especially concerning the detrital food web) of marine
      environments. 

PMID- 26203653
TI  - Primary Motor Cortex Representation of Handgrip Muscles in Patients with Leprosy.
AB  - BACKGROUND: Leprosy is an endemic infectious disease caused by Mycobacterium
      leprae that predominantly attacks the skin and peripheral nerves, leading to
      progressive impairment of motor, sensory and autonomic function. Little is known
      about how this peripheral neuropathy affects corticospinal excitability of
      handgrip muscles. Our purpose was to explore the motor cortex organization after
      progressive peripheral nerve injury and upper-limb dysfunction induced by leprosy
      using noninvasive transcranial magnetic stimulation (TMS). METHODS: In a cross
      sectional study design, we mapped bilaterally in the primary motor cortex (M1)
      the representations of the hand flexor digitorum superficialis (FDS), as well as
      of the intrinsic hand muscles abductor pollicis brevis (APB), first dorsal
      interosseous (FDI) and abductor digiti minimi (ADM). All participants underwent
      clinical assessment, handgrip dynamometry and motor and sensory nerve conduction
      exams 30 days before mapping. Wilcoxon signed rank and Mann-Whitney tests were
      performed with an alpha-value of p<0.05. FINDINGS: Dynamometry performance of the
      patients' most affected hand (MAH), was worse than that of the less affected hand
      (LAH) and of healthy controls participants (p = 0.031), confirming handgrip
      impairment. Motor threshold (MT) of the FDS muscle was higher in both hemispheres
      in patients as compared to controls, and lower in the hemisphere contralateral to
      the MAH when compared to that of the LAH. Moreover, motor evoked potential (MEP)
      amplitudes collected in the FDS of the MAH were higher in comparison to those of
      controls. Strikingly, MEPs in the intrinsic hand muscle FDI had lower amplitudes
      in the hemisphere contralateral to MAH as compared to those of the LAH and the
      control group. Taken together, these results are suggestive of a more robust
      representation of an extrinsic hand flexor and impaired intrinsic hand muscle
      function in the hemisphere contralateral to the MAH due to leprosy. CONCLUSION:
      Decreased sensory-motor function induced by leprosy affects handgrip muscle
      representation in M1.

PMID- 26203656
TI  - Mechanisms of Host Behavioral Change in Toxoplasma gondii Rodent Association.

PMID- 26203655
TI  - Molecular Framework of a Regulatory Circuit Initiating Two-Dimensional Spatial
      Patterning of Stomatal Lineage.
AB  - Stomata, valves on the plant epidermis, are critical for plant growth and
      survival, and the presence of stomata impacts the global water and carbon cycle.
      Although transcription factors and cell-cell signaling components regulating
      stomatal development have been identified, it remains unclear as to how their
      regulatory interactions are translated into two-dimensional patterns of stomatal
      initial cells. Using molecular genetics, imaging, and mathematical simulation, we
      report a regulatory circuit that initiates the stomatal cell-lineage. The circuit
      includes a positive feedback loop constituting self-activation of SCREAMs that
      requires SPEECHLESS. This transcription factor module directly binds to the
      promoters and activates a secreted signal, EPIDERMAL PATTERNING FACTOR2, and the
      receptor modifier TOO MANY MOUTHS, while the receptor ERECTA lies outside of this
      module. This in turn inhibits SPCH, and hence SCRMs, thus constituting a negative
      feedback loop. Our mathematical model accurately predicts all known stomatal
      phenotypes with the inclusion of two additional components to the circuit: an
      EPF2-independent negative-feedback loop and a signal that lies outside of the
      SPCH*SCRM module. Our work reveals the intricate molecular framework governing
      self-organizing two-dimensional patterning in the plant epidermis. 

PMID- 26203657
TI  - Random Sampling with Interspike-Intervals of the Exponential Integrate and Fire
      Neuron: A Computational Interpretation of UP-States.
AB  - Oscillations between high and low values of the membrane potential (UP and DOWN
      states respectively) are an ubiquitous feature of cortical neurons during slow
      wave sleep and anesthesia. Nevertheless, a surprisingly small number of
      quantitative studies have been conducted only that deal with this phenomenon's
      implications for computation. Here we present a novel theory that explains on a
      detailed mathematical level the computational benefits of UP states. The theory
      is based on random sampling by means of interspike intervals (ISIs) of the
      exponential integrate and fire (EIF) model neuron, such that each spike is
      considered a sample, whose analog value corresponds to the spike's preceding ISI.
      As we show, the EIF's exponential sodium current, that kicks in when balancing a
      noisy membrane potential around values close to the firing threshold, leads to a
      particularly simple, approximative relationship between the neuron's ISI
      distribution and input current. Approximation quality depends on the frequency
      spectrum of the current and is improved upon increasing the voltage baseline
      towards threshold. Thus, the conceptually simpler leaky integrate and fire neuron
      that is missing such an additional current boost performs consistently worse than
      the EIF and does not improve when voltage baseline is increased. For the EIF in
      contrast, the presented mechanism is particularly effective in the high
      conductance regime, which is a hallmark feature of UP-states. Our theoretical
      results are confirmed by accompanying simulations, which were conducted for input
      currents of varying spectral composition. Moreover, we provide analytical
      estimations of the range of ISI distributions the EIF neuron can sample from at a
      given approximation level. Such samples may be considered by any algorithmic
      procedure that is based on random sampling, such as Markov Chain Monte Carlo or
      message-passing methods. Finally, we explain how spike-based random sampling
      relates to existing computational theories about UP states during slow wave sleep
      and present possible extensions of the model in the context of spike-frequency
      adaptation. 

PMID- 26203658
TI  - Distinct Temporal Fingerprint for Cyclic Adenosine Monophosphate (cAMP) Signaling
      of Indole-2-carboxamides as Allosteric Modulators of the Cannabinoid Receptors.
AB  - ORG27569 (1) is an allosteric modulator of CB1. 1 produces a distinct cAMP
      temporal fingerprint with complex time-dependent modulation of agonist-mediated
      responses. The aim of this study was to characterize the cAMP signaling response
      of indole-2-carboxamides structurally correlated to 1 for both CB1 and CB2. We
      show that at CB1 1, 10, 13, and 18 display a delay in inhibiting CP55,940
      mediated cAMP inhibition, whereas compounds 7, 14, 15, 16, 20, and 22 act
      immediately. To further characterize this, compounds 1, 10, 13, 14, 15, 18, and
      20 were tested for their influence on CP55,940-mediated hyperpolarization in
      AtT20-hCB1 cells. Intriguingly, all compounds generated a response similar to
      that of 1, producing no decrease in CB1-mediated peak hyperpolarization at
      concentrations up to 10 MUM but enhancing the rate at which the channel
      repolarizes. Additionally, we show that compounds 5, 10, and 20 indole-2
      carboxamides modulate cAMP signaling through CB2. 

PMID- 26203659
TI  - Clinical features of amyotrophic lateral sclerosis in south-west China.
AB  - Our objective was to profile clinical features of amyotrophic lateral sclerosis
      (ALS); we performed a large sample, cross-sectional study based on a hospital
      registry of ALS in south-west China. Patients were coded in our tertiary referral
      centre from May 2006 to September 2014. Demographic data and disease-related
      parameters were collected. A total of 1131 patients were included. Mean age of
      onset was 54.3 +/- 11.6 years and the highest proportion of onset age (30.6%) was
      between 51 and 60 years. Male:female ratio was 1.45:1. Nearly 30% of the patients
      were young onset, and 20.3% of the patients were bulbar onset; only 35% received
      riluzole treatment. The young-onset patients had a higher educational level with
      a higher proportion performing manual labour and living in rural areas, and a
      lower proportion with bulbar onset than those who were older at onset. The bulbar
      onset patients were older at age of onset, with a lower proportion of males than
      spinal-onset patients. In conclusion, Chinese ALS patients may be younger at age
      of onset than Caucasian patients. Environmental and geographical factors are
      related to the occurrence of ALS. The large treatment gap indicated a pressing
      need for medical and financial support for Chinese ALS patients. 

PMID- 26203661
TI  - A Dutch family with autosomal recessively inherited lower motor neuron
      predominant motor neuron disease due to optineurin mutations.
AB  - Approximately 10% of motor neuron disease (MND) patients report a familial
      predisposition for MND. Autosomal recessively inherited MND is less common and is
      most often caused by mutations in the superoxide dismutase 1 (SOD1) gene. In
      2010, autosomal recessively inherited mutations in the optineurin (OPTN) gene
      were found in 1% of Japanese patients with sporadic amyotrophic lateral sclerosis
      (ALS). Autosomal dominantly inherited OPTN mutations have been described as a
      cause of primary open-angle glaucoma in the Netherlands and were also found in
      two Dutch sporadic MND patients. We report the first Dutch family with autosomal
      recessively inherited MND caused by mutations in the OPTN gene. 

PMID- 26203660
TI  - ALSUntangled No. 30: methylcobalamin.

PMID- 26203662
TI  - Stereoconvergent Negishi Arylations of Racemic Secondary Alkyl Electrophiles:
      Differentiating between a CF3 and an Alkyl Group.
AB  - In this report, we establish that a readily available nickel/bis(oxazoline)
      catalyst accomplishes a wide array of enantioconvergent cross-couplings of
      arylzinc reagents with CF3-substituted racemic secondary alkyl halides, a process
      that necessitates that the chiral catalyst be able to effectively distinguish
      between a CF3 and an alkyl group in order to provide good ee. We further
      demonstrate that this method can be applied without modification to the catalytic
      asymmetric synthesis of other families of fluorinated organic compounds. 

PMID- 26203663
TI  - Combined Theoretical and Experimental Study of Refractive Indices of Water
      Acetonitrile-Salt Systems.
AB  - We propose a simple theoretical formula for describing the refractive indices in
      binary liquid mixtures containing salt ions. Our theory is based on the Clausius
      Mossotti equation; it gives the refractive index of the mixture in terms of the
      refractive indices of the pure liquids and the polarizability of the ionic
      species, by properly accounting for the volume change upon mixing. The
      theoretical predictions are tested by extensive experimental measurements of the
      refractive indices for water-acetonitrile-salt systems for several liquid
      compositions, different salt species, and a range of salt concentrations.
      Excellent agreement is obtained in all cases, especially at low salt
      concentrations, with no fitting parameters. A simplified expression of the
      refractive index for low salt concentration is also given, which can be the
      theoretical basis for determination of salt concentration using refractive index
      measurements. 

PMID- 26203664
TI  - Targeting lactate transport suppresses in vivo breast tumour growth.
AB  - BACKGROUND: Most cancers, including breast cancer, have high rates of glucose
      consumption, associated with lactate production, a process referred as "Warburg
      effect". Acidification of the tumour microenvironment by lactate extrusion,
      performed by lactate transporters (MCTs), is associated with higher cell
      proliferation, migration, invasion, angiogenesis and increased cell survival.
      Previously, we have described MCT1 up-regulation in breast carcinoma samples and
      demonstrated the importance of in vitro MCT inhibition. In this study, we
      performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in
      both normoxia and hypoxia conditions to validate the potential of lactate
      transport inhibition in breast cancer treatment. RESULTS: The effect of MCT
      knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration
      and invasion and induction of tumour xenografts in nude mice. MCT knockdown led
      to a decrease in in vitro tumour cell aggressiveness, with decreased lactate
      transport, cell proliferation, migration and invasion and, importantly, to an
      inhibition of in vivo tumour formation and growth. CONCLUSIONS: This work
      supports MCTs as promising targets in cancer therapy, demonstrates the
      contribution of MCTs to cancer cell aggressiveness and, more importantly, shows,
      for the first time, the disruption of in vivo breast tumour growth by targeting
      lactate transport.

PMID- 26203665
TI  - Endothelial-like malignant glioma cells in dynamic three dimensional culture
      identifies a role for VEGF and FGFR in a tumor-derived angiogenic response.
AB  - AIMS: Recent studies have observed that cells from high-grade glial tumors are
      capable of assuming an endothelial phenotype and genotype, a process termed
      'vasculogenic mimicry' (VM). Here we model and manipulate VM in dynamic 3
      dimensional (3D) glioma cultures. METHODS: The Rotary Cell Culture System (RCCS)
      was used to derive large macroscopic glioma aggregates, which were sectioned for
      immunohistochemistry and RNA extracted prior to angiogenic array-PCR. RESULTS: A
      3D cell culture induced microenvironment (containing only glial cells) is
      sufficient to promote expression of the endothelial markers CD105, CD31 and vWF
      in a proportion of glioma aggregates in vitro. Many pro-angiogenic genes were
      upregulated in glioma aggregates and in primary explants and glioma cells were
      capable of forming tubular-like 3D structures under endothelial-promoting
      conditions. Competitive inhibition of either vascular endothelial growth factor
      or fibroblast growth factor receptor was sufficient to impair VM and downregulate
      the tumor-derived angiogenic response, whilst impairing tumor cell derived tubule
      formation. Glioma xenografts using the same cells reveal tumor-derived vessel
      like structures near necrotic areas, consistent with widespread tumor-derived
      endothelial expression in primary glioma tissue. CONCLUSIONS: Our findings
      support studies indicating that tumor-derived endothelial cells arise in gliomas
      and describe a dynamic 3D culture as a bona fide model to interrogate the
      molecular basis of this phenomenon in vitro. Resistance to current anti
      angiogenic therapies and the contribution of tumor derived endothelial cells to
      such resistance are amenable to study using the RCCS.

PMID- 26203667
TI  - Playing Tic-Tac-Toe with a Sugar-Based Molecular Computer.
AB  - Today, molecules can perform Boolean operations and circuits at a level of higher
      complexity. However, concatenation of logic gates and inhomogeneous inputs and
      outputs are still challenging tasks. Novel approaches for logic gate integration
      are possible when chemical programming and software programming are combined.
      Here it is shown that a molecular finite automaton based on the concatenated
      implication function (IMP) of a fluorescent two-component sugar probe via a
      wiring algorithm is able to play tic-tac-toe. 

PMID- 26203666
TI  - Human stromal cells are required for an anti-breast cancer effect of zoledronic
      acid.
AB  - Previous studies suggested that bisphosphonate zoledronic acid exerts an anti
      tumor effect by interacting with the microenvironment. In this study, we aimed to
      elucidate the mechanism behind the anti-breast cancer effect of zoledronic
      acid.Here we showed that zoledronic acid did not influence in vitro human breast
      cancer cell survival, but did affect human stromal cell survival. Breast cancer
      cell death in co-culture with stromal cells was analyzed in vitro by fluorescent
      microscopy and flowcytometry analysis. In co-culture, the addition of stromal
      cells to breast cancer cells induced tumor cell death by zoledronic acid, which
      was abolished by transforming growth factor (TGF)-beta. In the in vivo chicken
      chorioallantoic membrane model, zoledronic acid reduced the breast cancer cells
      fraction per tumor only in the presence of human stromal cells. Zoledronic acid
      decreased TGF-beta excretion by stromal cells and co-cultures. Moreover,
      supernatant of zoledronic acid treated stromal cells reduced phospho-Smad2
      protein levels in breast cancer cells. Thus, zoledronic acid exerts an anti
      breast cancer effect via stromal cells, accompanied by decreased stromal TGF-beta
      excretion and reduced TGF-beta signaling in cancer cells. 

PMID- 26203668
TI  - Diastereoselective Synthesis of syn-beta-Lactams Using Rh-Catalyzed Reductive
      Mannich-Type Reaction of alpha,beta-Unsaturated Esters.
AB  - The combination of Et2Zn and RhCl(PPh3)3 led to the facile generation of a
      rhodium-hydride complex (Rh-H) that catalyzed the 1,4-reduction of alpha,beta
      unsaturated esters. The resulting rhodium enolate performed as a Reformatsky-type
      reagent and reacted with various imines to give syn-beta-lactams in good to
      excellent yields with high diastereoselectivity. 

PMID- 26203669
TI  - Determination of Effective Particle Density for Sterically Stabilized Carbon
      Black Particles: Effect of Diblock Copolymer Stabilizer Composition.
AB  - Two poly(styrene-b-hydrogenated isoprene) (PS-PEP) copolymers and a poly(styrene
      b-hydrogenated butadiene) (PS-PB) diblock copolymer of differing polystyrene
      content (20, 28 or 35 mol %) and molecular weight (117-183 kg mol(-1)) are
      examined. These copolymers form star-like micelles in n-dodecane, as judged by
      TEM, DLS, and SAXS studies. At ambient temperature, such micelles are known to
      adsorb intact onto a model colloidal substrate such as carbon black, conferring a
      high degree of dispersion (Growney, D. J.; Mykhaylyk, O. O.; Armes, S. P.
      Langmuir 2014, 30, 6047). Isotherms for micellar adsorption on carbon black at 20
      degrees C are constructed using a supernatant depletion assay based on UV
      spectroscopy by utilizing the aromatic chromophore in the polystyrene block.
      Perhaps surprisingly, the diblock copolymer with the lowest polystyrene content
      has the strongest affinity for the carbon black particles. Assuming that the star
      like diblock copolymer micelles adsorb onto carbon black to form hemi-micelles
      with a stabilizer layer thickness equal to the mean micelle radius, the effective
      particle density of the resulting sterically stabilized carbon black particles in
      n-dodecane can be estimated from the SAXS micelle dimensions based on geometric
      considerations. As an approximation, a spherical core-shell morphology was
      assumed, and the primary grain size of the carbon black particles was determined
      to be 74 nm diameter as judged by BET surface area analysis. Using this approach,
      effective particle densities of 0.90, 0.91, and 0.92 g cm(-3) were calculated for
      sterically stabilized carbon black particles prepared using the PS-PB20, PS
      PEP28, and PS-PEP35 diblock copolymers, respectively. These densities are
      significantly lower than that of carbon black (1.89 g cm(-3)), which indicates
      that the sterically stabilized carbon black particles are substantially solvated.
      Since the rate of sedimentation of the sterically stabilized carbon black
      particles depends on the density difference between the effective particle
      density and that of n-dodecane (0.75 g cm(-3)), particle size analysis via
      analytical centrifugation incurs large sizing errors unless the above corrected
      effective particle densities are utilized. This is important because analytical
      centrifugation is a highly convenient technique for assessing the relative degree
      of dispersion of sterically stabilized carbon black particles, which are utilized
      to inkjet inks and coatings formulations. 

PMID- 26203670
TI  - Charge-Induced Second-Harmonic Generation in Bilayer WSe2.
AB  - Controlling nonlinear light-matter interaction is important from a fundamental
      science point of view as well as a basis for future optoelectronic devices.
      Recent advances in two-dimensional crystals have created opportunities to
      manipulate nonlinear processes electrically. Here we report a strong second
      harmonic generation (SHG) in a 2D WSe2 bilayer crystal caused by a back gate
      field. This unusual process takes place only when the gate polarity causes charge
      accumulation rather than depletion. Analysis based on a bond-charge model traces
      the origin of SHG to the nonuniform field distribution within a single monolayer,
      caused by the accumulated submonolayer screening charge in the tungsten plane. We
      name this phenomenon charge-induced SHG (CHISHG), which is fundamentally
      different from the field- or current-induced SHG. Our findings provide a
      potentially valuable technique for understanding and noninvasive probing of
      charge and current distributions in future low dimensional electronic devices. 

PMID- 26203671
TI  - Outcomes and Prognostic Features of Patients With Influenza Requiring
      Hospitalization and Receiving Early Antiviral Therapy: A Prospective Multicenter
      Cohort Study.
AB  - BACKGROUND: In Japan, the routine use of early antiviral therapy for patients
      with influenza is standard. METHODS: This multicenter prospective cohort
      evaluation of hospitalized patients with laboratory-confirmed influenza
      identified prognostic factors among the patients receiving antiviral therapy.
      RESULTS: Of 1,345 patients with influenza (766 pediatric, 579 adult), excluding
      those aged < 1 year (who are not approved for antiviral therapy), 97.7% (1,224 of
      1,253) received antiviral therapy. Among the adult patients, 24 (4.1%) died
      within 30 days, whereas none of the pediatric patients died. Five hundred twenty
      eight (91.2%) adult patients had influenza A, 509 (87.9%) had a chronic
      underlying illness, and 211 (36.4%) had radiographically confirmed pneumonia.
      Twenty of the 24 patients who died had pneumonia of the following etiologies:
      Streptococcus pneumoniae (12.3%); Staphylococcus aureus (10.9%), including
      methicillin-resistant S aureus (MRSA) 3.3%; Enterobacteriaceae (8.1%); and
      Pseudomonas aeruginosa (3.3%). Of the adult patients, 151 were classified as
      having community-acquired pneumonia (CAP) and 60 as having health-care-associated
      pneumonia (HCAP). Inappropriate therapy was more common in HCAP than in CAP
      (15.2% vs 2%, P = .001). Potential multidrug-resistant (MDR) pathogens were more
      common (21.7% vs 2.6%, P < .001) in patients with HCAP, particularly MRSA (10% vs
      0.7%, P = .002) and P aeruginosa (8.3% vs 1.3%, P = .021). Using Cox proportional
      hazards modeling with prescribed independent variables, male sex, severity score,
      serum albumin levels (malnutrition), and pneumonia were associated with survival
      30 days from the onset of influenza. CONCLUSIONS: Among the prognostic factors,
      malnutrition and pneumonia are amenable to medical intervention. An opportunity
      exists to improve empirical therapy for patients with HCAP and influenza. TRIAL
      REGISTRY: Japan Medical Association Center for Clinical Trials; No.: JMA
      IIA00123; URL: http://www.jmacct.med.or.jp/en/.

PMID- 26203672
TI  - Graphene Oxide-Supported Ag Nanoplates as LSPR Tunable and Reproducible
      Substrates for SERS Applications with Optimized Sensitivity.
AB  - Nanoparticles and nanohybrids with well-defined structures, along with tunable
      localized surface plasmon resonance (LSPR) properties and optimized sensitivity,
      are crucial and highly desired for surface-enhanced Raman spectroscopy (SERS)
      applications. In this article, we report on a very promising and flexible SERS
      platforms with a tunable LSPR response and sensitivity based on Ag nanoplates and
      graphene oxide (GO). The SERS detection sensitivity can be easily optimized and
      significantly improved by fine-tuning the LSPR band of the Ag nanoplate/GO
      substrates (to enhance the SERS response) during sample preparation. We applied
      the as-prepared SERS platform for sensitive SERS detection of 4-mercaptobenzoic
      acid and 4-aminothiophenol and found that the SERS signal varied markedly (by ~10
      15-fold) with the fine-tuning of the LSPR band. The SERS enhancement factor of
      the Ag nanoplate/GO complexes was more than 10(4) times larger than that obtained
      using spherical Ag nanoparticles. The as-prepared Ag nanoplate/GO platforms,
      because of their excellent stability and tunable LSPR properties, will find
      promising practical SERS applications. 

PMID- 26203674
TI  - Gold Nanowire Bundles Grown Radially Outward from Silicon Micropillars.
AB  - One-dimensional (1D) micro- and nanostructures have become increasingly popular
      because of their tremendous prospect in various applications. While the design
      and fabrication of these structures from a single component in two-dimensional
      (2D) arrays is common, the attainment of hierarchical three-dimensional (3D)
      architectures made up of multicomponent one-dimensional structures is rare.
      Herein we report, for the first time, the lateral growth of gold nanowires from
      the sidewalls of substrate grown silicon micropillars to form a unique "wire-on
      pillar" architecture. Unlike zero-dimensional (0D) point-like, 1D linear, and 2D
      planar Au structures, the obtained 3D "wire-on-pillar" Au architecture provides
      abundant hotspots between adjacent Au wires, which led to remarkably high surface
      enhanced Raman scattering (SERS) signals. 

PMID- 26203673
TI  - Caffeine Cytochrome P450 1A2 Metabolic Phenotype Does Not Predict the Metabolism
      of Heterocyclic Aromatic Amines in Humans.
AB  - 2-Amino-1-methylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx) are carcinogenic heterocyclic aromatic amines (HAAs) formed
      in well-done cooked meats. Chemicals that induce cytochrome P450 (P450) 1A2, a
      major enzyme involved in the bioactivation of HAAs, also form in cooked meat.
      Therefore, well-done cooked meat may pose an increase in cancer risk because it
      contains both inducers of P450 1A2 and procarcinogenic HAAs. We examined the
      influence of components in meat to modulate P450 1A2 activity and the metabolism
      of PhIP and MeIQx in volunteers during a 4 week feeding study of well-done cooked
      beef. The mean P450 1A2 activity, assessed by caffeine metabolic phenotyping,
      ranged from 6.3 to 7.1 before the feeding study commenced and from 9.6 to 10.4
      during the meat feeding period: the difference in means was significant (P <
      0.001). Unaltered PhIP, MeIQx, and their P450 1A2 metabolites, N(2)-(beta-1
      glucosiduronyl)-2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (HON
      PhIP-N(2)-Gl); N3-(beta-1-glucosiduronyl)-2-(hydroxyamino)-1-methyl-6
      phenylimidazo[4,5-b]pyridine (HON-PhIP-N3-Gl); 2-amino-3-methylimidazo-[4,5
      f]quinoxaline-8-carboxylic acid (IQx-8-COOH); and 2-amino-8-(hydroxymethyl)-3
      methylimidazo[4,5-f]quinoxaline (8-CH2OH-IQx) were measured in urine during days
      2, 14, and 28 of the meat diet. Significant correlations were observed on these
      days between the levels of the unaltered HAAs and their oxidized metabolites,
      when expressed as percent of dose ingested or as metabolic ratios. However, there
      was no statistically significant correlation between the caffeine P450 1A2
      phenotype and any urinary HAA biomarker. Although the P450 1A2 activity varied by
      greater than 20-fold among the subjects, there was a large intraindividual
      variation of the P450 1A2 phenotype and inconsistent responses to inducers of
      P450 1A2. The coefficient of variation of the P450 1A2 phenotype within
      individual ranged between 1 to 112% (median = 40%) during the entire course of
      the study. The caffeine metabolic phenotype for P450 1A2 was a poor predictor of
      oxidative urinary metabolites of PhIP and MeIQx and may not be a reliable measure
      to assess the role of HAAs in cancer risk. 

PMID- 26203675
TI  - Manganese-Vanadate Hybrids: Impact of Organic Ligands on Their Structures,
      Thermal Stabilities, Optical Properties, and Photocatalytic Activities.
AB  - Manganese(II)-vanadate(V)/organic hybrids were prepared in high purity using four
      different N-donor organic ligands (2,6:2',2"-terpyridine = terpy, 2,2'
      bipyrimidine = bpym, o-phenanthroline = o-phen, and 4,4'-bipyridine = 4,4'-bpy),
      and their crystalline structures, thermal stabilities, optical properties,
      photocatalytic activities and electronic structures were investigated as a
      function of the organic ligand. Hydrothermal reactions were employed that
      targeted a 1:2 molar ratio of Mn(II)/V(V), yielding four hybrid solids with the
      compositions of Mn(terpy)V2O6.H2O (I), Mn2(bpym)V4O12.0.6H2O (II), Mn(H2O)(o
      phen)V2O6 (III), and Mn(4,4'-bpy)V2O6.1.16H2O (IV). The inorganic component
      within these hybrid compounds, that is, [MnV2O6], forms infinite chains in I and
      layers in II, III, and IV. In each case, the organic ligand preferentially
      coordinates to the Mn(II) cations within their respective structures, either as
      chelating and three-coordinate (mer isomer in I) or two-coordinate (cis isomers
      in II and III), or as bridging and two coordinate (trans isomer in IV). The
      terminating ligands in I (terpy) and III (o-phen) yield nonbridged "MnV2O6"
      chains and layers, respectively, while the bridging ligands in II (bpym) and IV
      (4,4'-bpy) result in three-dimensional, pillared hybrid networks. The
      coordination number of the ligand, that is, two- or three-coordinate, has the
      predominant effect on the dimensionality of the inorganic component, while the
      connectivity of the combined metal-oxide/organic network is determined by the
      chelating versus bridging ligand coordination modes. Each hybrid compound
      decomposes into crystalline MnV2O6 upon heating in air with specific surface
      areas from ~7 m(2)/g for III to ~41 m(2)/g for IV, depending on the extent of
      structural collapse as the lattice water is removed. All hybrid compounds exhibit
      visible-light bandgap sizes from ~1.7 to ~2.0 eV, decreasing with the increased
      dimensionality of the [MnV2O6] network in the order of I > II ~ III > IV. These
      bandgap sizes are smaller by ~0.1-0.4 eV in comparison to related vanadate
      hybrids, owing to the addition of the higher-energy 3d orbital contributions from
      the Mn(II) cations. Each compound also exhibits temperature-dependent
      photocatalytic activities for hydrogen production under visible-light irradiation
      in 20% methanol solutions, with threshold temperatures of ~30  degrees C for III,
      ~36  degrees C for I, and ~40  degrees C for II, IV, and V4O10(o-phen)2. Hydrogen
      production rates are ~142 MUmol H2 g(-1).h(-1), ~673 MUmol H2 g(-1).h(-1), ~91
      MUmol H2 g(-1).h(-1), and ~218 MUmol H2 g(-1).h(-1) at 40  degrees C, for I, II,
      III, and IV, respectively, increasing with the oxide/organic network
      connectivity. In contrast, the related V4O10(o-phen)2 exhibits a much lower
      photocatalytic rate of ~36 H2 g(-1).h(-1). Electronic structure calculations
      based on density-functional theory methods show that the valence band edges are
      primarily derived from the half-filled Mn 3d(5) orbitals in each, while the
      conduction band edges are primarily comprised of contributions from the empty V
      3d(0) orbitals in I and II and from ligand pi* orbitals in III. Thus, the
      coordinating organic ligands are shown to significantly affect the local and
      extended structural features, which has elucidated the underlying relationships
      to their photocatalytic activities, visible-light bandgap sizes, electronic
      structures, and thermal stabilities. 

PMID- 26203677
TI  - ?

PMID- 26203678
TI  - ?

PMID- 26203679
TI  - ?

PMID- 26203676
TI  - Spatiotemporal Targeting of a Dual-Ligand Nanoparticle to Cancer Metastasis.
AB  - Various targeting strategies and ligands have been employed to direct
      nanoparticles to tumors that upregulate specific cell-surface molecules. However,
      tumors display a dynamic, heterogeneous microenvironment, which undergoes
      spatiotemporal changes including the expression of targetable cell-surface
      biomarkers. Here, we investigated a dual-ligand nanoparticle to effectively
      target two receptors overexpressed in aggressive tumors. By using two different
      chemical specificities, the dual-ligand strategy considered the spatiotemporal
      alterations in the expression patterns of the receptors in cancer sites. As a
      case study, we used two mouse models of metastasis of triple-negative breast
      cancer using the MDA-MB-231 and 4T1 cells. The dual-ligand system utilized two
      peptides targeting P-selectin and alphavbeta3 integrin, which are functionally
      linked to different stages of the development of metastatic disease at a distal
      site. Using in vivo multimodal imaging and post mortem histological analyses,
      this study shows that the dual-ligand nanoparticle effectively targeted
      metastatic disease that was otherwise missed by single-ligand strategies. The
      dual-ligand nanoparticle was capable of capturing different metastatic sites
      within the same animal that overexpressed either receptor or both of them.
      Furthermore, the highly efficient targeting resulted in 22% of the injected dual
      ligand nanoparticles being deposited in early-stage metastases within 2 h after
      injection. 

PMID- 26203680
TI  - ?

PMID- 26203682
TI  - ?

PMID- 26203681
TI  - ?

PMID- 26203683
TI  - Ozone-Induced Type 2 Immunity in Nasal Airways. Development and Lymphoid Cell
      Dependence in Mice.
AB  - Inhalation exposures to ozone commonly encountered in photochemical smog cause
      airway injury and inflammation. Elevated ambient ozone concentrations have been
      epidemiologically associated with nasal airway activation of neutrophils and
      eosinophils. In the present study, we elucidated the temporal onset and lymphoid
      cell dependency of eosinophilic rhinitis and associated epithelial changes in
      mice repeatedly exposed to ozone. Lymphoid cell-sufficient C57BL/6 mice were
      exposed to 0 or 0.5 parts per million (ppm) ozone for 1, 2, 4, or 9 consecutive
      weekdays (4 h/d). Lymphoid cell-deficient, Rag2(-/-)Il2rg(-/-) mice were
      similarly exposed for 9 weekdays. Nasal tissues were taken at 2 or 24 hours after
      exposure for morphometric and gene expression analyses. C57BL/6 mice exposed to
      ozone for 1 day had acute neutrophilic rhinitis, with airway epithelial necrosis
      and overexpression of mucosal Ccl2 (MCP-1), Ccl11 (eotaxin), Cxcl1 (KC), Cxcl2
      (MIP-2), Hmox1, Il1b, Il5, Il6, Il13, and Tnf mRNA. In contrast, 9-day ozone
      exposure elicited type 2 immune responses in C57BL/6 mice, with mucosal mRNA
      overexpression of Arg1, Ccl8 (MCP-2), Ccl11, Chil4 (Ym2), Clca1 (Gob5), Il5,
      Il10, and Il13; increased density of mucosal eosinophils; and nasal epithelial
      remodeling (e.g., hyperplasia/hypertrophy, mucous cell metaplasia, hyalinosis,
      and increased YM1/YM2 proteins). Rag2(-/-)Il2rg(-/-) mice exposed to ozone for 9
      days, however, had no nasal pathology or overexpression of transcripts related to
      type 2 immunity. These results provide a plausible paradigm for the activation of
      eosinophilic inflammation and type 2 immunity found in the nasal airways of
      nonatopic individuals subjected to episodic exposures to high ambient ozone. 

PMID- 26203686
TI  - MicroRNA-125b and chemokine CCL4 expression are associated with calcific aortic
      valve disease.
AB  - Calcific aortic valve disease (CAVD) is a progressive pathological condition with
      no effective pharmacological therapy. To identify novel molecular pathways as
      potential targets for pharmacotherapy, we studied microRNA (miRNA) profiles of
      heavily stenotic aortic valves (AS). One of the most upregulated miRNAs in AS
      valves compared to control valves was miR-125b (1.4-fold; P < 0.05). To identify
      CAVD-related changes in gene expression, DNA microarray analysis was performed,
      including an intermediate fibro(sclero)tic stage of the disease. This revealed
      changes especially in genes related to inflammation and immune response,
      including chemokine (C-C motif) ligand 3 (CCL3) and 4 (CCL4). CCL3 mRNA level was
      increased 3.9-fold (P < 0.05) when AS valves were compared to control valves, and
      a 2.5-fold increase (P < 0.05) in CCL4 gene expression was observed when
      fibro(sclero)tic valves were compared to control valves. Both CCL3 and CCL4
      localized to macrophages by immunofluorescence. To identify chemokine-miRNA
      target pairs, data from miRNA target prediction databases were combined with
      valvular miRNA and mRNA expression profiles. MiR-125b was computationally
      predicted to target CCL4, as confirmed experimentally in cultured human THP-1
      macrophages. Collectively, miR-125b and CCL4 appear to be involved in the
      progression of CAVD and may offer novel therapeutic and diagnostic strategies
      related to this disease. 

PMID- 26203687
TI  - Novel RGD containing, temozolomide-loading nanostructured lipid carriers for
      glioblastoma multiforme chemotherapy.
AB  - CONTEXT: Glioblastoma multiforme (GBM) is the most common malignant brain tumor
      originating in the central nervous system. Efficient delivery of therapeutic
      molecules to the cells and tissues is a difficult challenge. OBJECTIVE: Arginine
      glycine-aspartic acid peptide (RGD)-modified nanostructured lipid carriers (NLCs)
      were used for the delivery of temozolomide (TMZ) into the GBM to provide a new
      paradigm in gliomatosis cerebri treatment. METHODS: RGD-conjugated polyethylene
      glycol-b-distearoylphosphatidylethanolamine (PEG-DSPE) was synthesized. RGD
      containing, TMZ-loaded NLCs (RGD-TMZ/NLCs) were prepared. Their particle size,
      zeta potential, drug encapsulation efficiency (EE) and drug release behavior were
      evaluated. In vitro cytotoxicity study of TMZ/NLCs was tested in U87 malignant
      glioma cells (U87MG cells). In vivo antitumor efficacy of the carriers was
      evaluated on mice bearing GBM model. RESULTS: The U87MG cells were successfully
      inhibited by RGD-TMZ/NLCs in vitro. RGD-TMZ/NLCs also displayed the highest
      antitumor efficacy in vivo than all the other formulations used for comparison.
      CONCLUSION: RGD-TMZ/NLCs were efficient in selective delivery of TMZ into U87MG
      cells, and inhibition efficacy is high. These RGD-modified vectors could be a
      superior drug delivery nano-system to achieve therapeutic efficacy, and this
      research could be a new promising strategy for treatment in malignant gliomatosis
      cerebri.

PMID- 26203688
TI  - Curcumin-guided nanotherapy: a lipid-based nanomedicine for targeted drug
      delivery in breast cancer therapy.
AB  - BACKGROUND: Delivery of anti-cancer drugs into the cancer cells or tissues by
      multifunctional nanocarriers may provide a new paradigm in cancer treatment. In
      this study, folate (FA) decorated nanostructured lipid carriers (NLCs) were
      constructed as nanomedicine for the delivery of curcumin (CUR). METHODS: CUR
      loaded NLCs (CUR-NLCs) were prepared. FA containing polyethylene glycol (PEG)
      distearoylphosphatidylethanolamine (DSPE) (FA-PEG-DSPE) was synthesized and used
      for the decoration of CUR-NLCs. Their particle size, zeta potential, and drug
      encapsulation efficiency (EE) were evaluated. In vitro cytotoxicity study FA
      decorated CUR-NLCs (FA-CUR-NLCs) was tested in MCF-7 human breast cancer cells
      (MCF-7 cells). In vivo anti-tumor efficacies of the carriers were evaluated on
      mice bearing breast cancer model. RESULTS: The optimum FA-CUR-NLCs formulations
      with the particle size of 127 nm and with a +13 mV surface charge. The growth of
      MCF-7 cells in vitro was obviously inhibited. FA-CUR-NLCs also displayed the best
      anti-tumor activity than other formulations in vivo. CONCLUSION: The results
      demonstrated that FA-CUR-NLCs were efficient in selective delivery to cancer
      cells over-expressing FA receptors (FRs). Also FA-CUR-NLCs transfer CUR to the
      breast cancer cells, enhance the anti-tumor capacity. Thus, FA-CUR-NLCs could
      prove to be a superior nanomedicine to achieve tumor therapeutic efficacy.

PMID- 26203689
TI  - Targeted nanomedicine for prostate cancer therapy: docetaxel and curcumin co
      encapsulated lipid-polymer hybrid nanoparticles for the enhanced anti-tumor
      activity in vitro and in vivo.
AB  - OBJECTIVE: Docetaxel (DTX) remains the only effective drug for prolonging
      survival and improving quality of life of metastatic castration-resistant
      prostate cancer (mCRPC) patients. Combination anticancer therapy encapsulating
      DTX and another extract of traditional Chinese medicine is one nano-sized drug
      delivery system promising to generate synergistic anticancer effects, to maximize
      the treatment effect, and to overcome multi-drug resistance. The purpose of this
      study is to construct lipid-polymer hybrid nanoparticles (LPNs) as nanomedicine
      for co-encapsulation of DTX and curcumin (CUR). METHODS: DTX and CUR co
      encapsulated LPNs (DTX-CUR-LPNs) were constructed. DTX-CUR-LPNs were evaluated in
      terms of particles size, zeta potential, drug encapsulation, and drug delivery.
      The cytotoxicity of the LPNs was evaluated on PC-3 human prostate carcinoma cells
      (PC3 cells) by MTT assays. In vivo anti-tumor effects were observed on the PC3
      tumor xenografts in mice. RESULTS: The particle size of DTX-CUR-LPNs was 169.6 nm
      with a positive zeta potential of 35.7 mV. DTX-CUR-LPNs showed highest
      cytotoxicity and synergistic effect of two drugs in tumor cells in vitro. In mice
      bearing PC-3 tumor xenografts, the DTX-CUR-LPNs inhibited tumor growth to a
      greater extent than other contrast groups, without inducing any obvious side
      effects. CONCLUSION: According to these results, the novel nanomedicine offers
      great promise for the dual drugs delivery to the prostate cancer cells, showing
      the potential of synergistic combination therapy for prostate cancer.

PMID- 26203690
TI  - A novel ligand conjugated nanoparticles for oral insulin delivery.
AB  - In order to enhance the interaction between nanocarrier and gastrointestinal
      epithelial cells, we developed nanoparticles (NPs) modified with targeting ligand
      FQSIYPpIK (FQS), which specifically interact with integrin alphavbeta3 receptor
      expressing on the intestinal epithelium. The targeting NPs were prepared by
      coating the insulin-loaded poly(lactide-co-glycolide)-monomethoxy
      poly(polyethylene glycol) micelle cores with FQS modified trimethyl chitosan
      chloride. In in vitro study, the fabricated NPs showed ameliorated drug release
      profile and improved enzymatic stability compared with micelles alone. In the
      integrin alphavbeta3 receptor over-expressed Caco-2 cells model, FQS modified NPs
      exhibited significantly accelerated intracellular uptake due to the active ligand
      receptor mediation. Meanwhile, the targeting NPs also showed enhanced transport
      across the Caco-2 monolayer cells via both transcellular and paracellular
      pathways. Besides, orally administered FQS modified NPs produced a prominent
      hypoglycemic response and an increase of the serum insulin concentration in
      diabetic rats. Both in vitro and in vivo results demonstrated the FQS peptide
      modified NPs as promising intestinal cell-targeting nanocarriers for efficient
      oral delivery of insulin. 

PMID- 26203691
TI  - Vincristine and temozolomide combined chemotherapy for the treatment of glioma: a
      comparison of solid lipid nanoparticles and nanostructured lipid carriers for
      dual drugs delivery.
AB  - CONTEXT: Glioma is a common malignant brain tumor originating in the central
      nervous system. Efficient delivery of therapeutic agents to the cells and tissues
      is a difficult challenge. Co-delivery of anticancer drugs into the cancer cells
      or tissues by multifunctional nanocarriers may provide a new paradigm in cancer
      treatment. OBJECTIVE: In this study, solid lipid nanoparticles (SLNs) and
      nanostructured lipid carriers (NLCs) were constructed for co-delivery of
      vincristine (VCR) and temozolomide (TMZ) to develop the synergetic therapeutic
      action of the two drugs. The antitumor effects of these two systems were compared
      to provide a better choice for gliomatosis cerebri treatment. METHODS: VCR- and
      TMZ-loaded SLNs (VT-SLNs) and NLCs (VT-NLCs) were formulated. Their particle
      size, zeta potential, drug encapsulation efficiency (EE) and drug loading
      capacity were evaluated. The single TMZ-loaded SLNs and NLCs were also prepared
      as contrast. Anti-tumor efficacies of the two kinds of carriers were evaluated on
      U87 malignant glioma cells and mice bearing malignant glioma model. RESULTS:
      Significantly better glioma inhibition was observed on NLCs formulations than
      SLNs, and dual drugs displayed the highest antitumor efficacy in vivo and in
      vitro than all the other formulations used. CONCLUSION: VT-NLCs can deliver VCR
      and TMZ into U87MG cells more efficiently, and inhibition efficacy is higher than
      VT-SLNs. This dual drugs-loaded NLCs could be an outstanding drug delivery system
      to achieve excellent therapeutic efficiency for the treatment of malignant
      gliomatosis cerebri.

PMID- 26203692
TI  - Breast cancer targeted chemotherapy based on doxorubicin-loaded bombesin peptide
      modified nanocarriers.
AB  - CONTEXT: Breast cancer is the most common cancer in female population. Breast
      cancer chemotherapy using doxorubicin (DOX) is well illustrated. However, a
      significant obstacle for successful chemotherapy with DOX is multidrug resistant
      (MDR) in breast cancer cells. Targeted nanocarriers have emerged as frontier
      research for the improvement of cancer chemotherapy. OBJECTIVE: Bombesin (Bn)
      modified, DOX-loaded solid lipid nanoparticles (Bn-DOX/SLNs) were constructed.
      Doxorubicin-resistant MCF-7/MDR human breast cancer cells and the cancer animal
      models were applied for the evaluation of the in vitro and in vivo anti-tumor
      effect of Bn-DOX/SLNs. METHODS: Bn-conjugated lipids were synthesized. DOX was
      then loaded into Bn-modified SLNs. The physicochemical properties of the Bn
      DOX/SLNs were investigated by particle size and zeta potential measurement, drug
      loading and drug-entrapment efficiency, and in vitro drug release behavior. In
      vitro cytotoxicity against MCF-7/MDR cells was investigated, and in vivo anti
      tumor of SLNs was evaluated in human breast cancer mice models. RESULTS: Bn
      DOX/SLNs showed an excellent in vitro cytotoxicity and in vivo anti-tumor effect
      both in MCF-7/MDR breast cancer cells and breast cancer animal model. CONCLUSION:
      The results demonstrated that Bn-DOX/SLNs reversed the resistance of doxorubicin,
      suggesting that chemotherapy using this kind of targeted nanocarriers may benefit
      human breast MDR cancer therapy.

PMID- 26203693
TI  - Medical adhesive-related skin injury: VADS and dressings.

PMID- 26203694
TI  - Outpatient antimicrobial therapy services.

PMID- 26203695
TI  - Proactive placement of peripherally inserted central catheters.

PMID- 26203696
TI  - Teaching competency in vascular access securement.

PMID- 26203697
TI  - Closed systems for drug delivery: a necessity, not an option.

PMID- 26203698
TI  - Rising Star in IV Therapy: BJN AWARD RUNNER UP.

PMID- 26203699
TI  - Learning from failure to improve practice.

PMID- 26203700
TI  - Effectiveness of electrocardiographic guidance in CVAD tip placement.
AB  - BACKGROUND: International standard practice for the correct confirmation of the
      central venous access device is the chest X-ray. The intracavitary
      electrocardiogram-based insertion method is radiation-free, and allows real-time
      placement verification, providing immediate treatment and reduced requirement for
      post-procedural repositioning. METHODS: Relevant databases were searched for
      prospective randomised controlled trials (RCTs) or quasi RCTs that compared the
      effectiveness of electrocardiogram-guided catheter tip positioning with placement
      using surface-anatomy-guided insertion plus chest X-ray confirmation. The primary
      outcome was accurate catheter tip placement. Secondary outcomes included
      complications, patient satisfaction and costs. RESULTS: Five studies involving
      729 participants were included. Electrocardiogram-guided insertion was more
      accurate than surface anatomy guided insertion (odds ratio: 8.3; 95% confidence
      interval (CI) 1.38; 50.07; p=0.02). There was a lack of reporting on
      complications, patient satisfaction and costs. CONCLUSION: The evidence suggests
      that intracavitary electrocardiogram-based positioning is superior to surface
      anatomy-guided positioning of central venous access devices, leading to
      significantly more successful placements. This technique could potentially remove
      the requirement for post-procedural chest X-ray, especially during peripherally
      inserted central catheter (PICC) line insertion.

PMID- 26203701
TI  - Acute mental health service use by patients with severe mental illness after
      discharge to primary care in South London.
AB  - BACKGROUND: To return the patients to primary care is arguably the desired
      service outcome for community mental health teams (CMHTs). AIMS: To assess acute
      mental health service use (hospitalisation or Home Treatment Team) by people with
      severe mental illness following discharge to primary care. METHOD: Retrospective
      cohort study comparing receipt and duration of acute care by 98 patients in the
      two years following discharge to primary care from CMHT, with a cohort of 92
      patients transferred to another CMHT. RESULTS: The discharged group was
      significantly more stable on clinical measures. Fifty-seven (58.2%) patients were
      re-referred after median 39 weeks, with 35 (60.3%) in crisis. The difference in
      acute service use between discharged patients (27.9 days/patient) and transferred
      patients (31.7 days/patient) was not significant. Hospitalisation in the two
      years prior to discharge or transfer increased the odds of re-referral (OR 3.93,
      95% CI 1.44-14.55), subsequent acute service use (OR 1.02, 95% CI 1.01-1.03) and
      duration of input (0.45 extra days/patient, 95% CI 0.22-0.68). CONCLUSIONS: The
      majority of the discharged patients were re-referred to mental health services.
      Although these were more stable, there was no difference from the transferred
      group on acute service use. Further support may be required in primary care to
      maintain stability.

PMID- 26203702
TI  - Ventilator-Associated Pneumonia in Pediatric Traumatic Brain Injury.
AB  - Ventilator-associated pneumonia (VAP) is a common occurrence among intubated
      pediatric traumatic brain injury (TBI) patients. However, little is known about
      the epidemiology, risk factors, and microbiology of VAP in pediatric TBI. We
      reviewed a cohort of 119 pediatric moderate-to-severe TBI patients and identified
      42 with VAP by positive protected bronchial brush specimens. Location of
      intubation, severity of injury, and antibiotic administration within 2 days after
      injury were not associated with VAP. Most treatments for elevated intracranial
      pressure were associated with increased risk of VAP; however, in a multi-variable
      analysis barbiturate coma (hazard ratio [HR], 3.2; 95% confidence interval [CI]
      1.4-7.3), neuromuscular blockade (NMBA; HR, 3.4; 95% CI 1.6-7.3), and use of a
      cooling blanket for euthermia (HR 2.4; 95% CI 1.1-5.5) remained independently
      associated with VAP. Most VAP (55%) occurred prior to hospital Day 4 and only 7%
      developed VAP after Day 7. Methicillin-sensitive Staphylococcus aureus (34%),
      Haemophilus influenzae (22%), and Streptococcus pneumoniae (15%) were the most
      common organisms, comprising 71% of isolated pathogens (36% of infections were
      polymicrobial). Patients with VAP had significantly longer intensive care unit
      and hospital stays, as well as increased risk of chronic care needs after
      discharge, but not mortality. VAP is a common occurrence in pediatric TBI
      patients, and early empiric therapy for patients requiring barbiturate infusion,
      NMBA, or use of a cooling blanket could mitigate morbidity.

PMID- 26203703
TI  - Science to Practice: The Changing Face of Local Tumor Therapies-Do We Have to
      Think Systemically When Treating Cancer Locally?
AB  - In this issue, Rozenblum et al ( 1 ) were able to demonstrate that radiofrequency
      (RF) ablation-induced liver regeneration promotes "off-target" tumorigenesis in a
      MDR2 knock-out mouse model of hepatocellular carcinoma (HCC) in the setting of
      chronic liver inflammation. In addition, the authors demonstrated that blocking
      liver regeneration with a c-met inhibitor might attenuate or eliminate potential
      tumorigenic effects. These results provide the rationale for combined therapeutic
      approaches of RF ablation followed by a systemic application of immunomodulatory
      drugs. 

PMID- 26203704
TI  - Reflect on the Past, Plan for the Future.

PMID- 26203705
TI  - Imaging for Staging and Response Assessment in Lymphoma.
AB  - Lymphoma comprises a heterogeneous group of diseases; remarkable advances have
      been made in diagnosis and treatment. Diagnostic imaging provides important
      information for staging and response assessment in patients with lymphoma. Over
      the years, staging systems have been refined, and dedicated criteria have been
      developed for evaluating response to therapy with both computed tomography (CT)
      and fluorine-18 fluorodeoxyglucose positron emission tomography (PET)/CT. The
      most recent system proposed for staging and response assessment, known as the
      Lugano classification, applies to both Hodgkin and non-Hodgkin lymphoma. The use
      of standardized criteria for staging and response assessment is important for
      making accurate treatment decisions and for determining the direction of further
      research. This review provides an overview of the updated CT and PET response
      criteria to familiarize the radiologist with the most important and clinically
      relevant aspects of lymphoma imaging. It also provides a short clinical update on
      lymphoma and the associated spectrum of imaging findings.

PMID- 26203706
TI  - State of the Art: Iterative CT Reconstruction Techniques.
AB  - Owing to recent advances in computing power, iterative reconstruction (IR)
      algorithms have become a clinically viable option in computed tomographic (CT)
      imaging. Substantial evidence is accumulating about the advantages of IR
      algorithms over established analytical methods, such as filtered back projection.
      IR improves image quality through cyclic image processing. Although all available
      solutions share the common mechanism of artifact reduction and/or potential for
      radiation dose savings, chiefly due to image noise suppression, the magnitude of
      these effects depends on the specific IR algorithm. In the first section of this
      contribution, the technical bases of IR are briefly reviewed and the currently
      available algorithms released by the major CT manufacturers are described. In the
      second part, the current status of their clinical implementation is surveyed.
      Regardless of the applied IR algorithm, the available evidence attests to the
      substantial potential of IR algorithms for overcoming traditional limitations in
      CT imaging.

PMID- 26203709
TI  - Oncogenesis: An "Off-Target" Effect of Radiofrequency Ablation.
AB  - PURPOSE: To compare hepatocellular carcinoma (HCC) development after
      radiofrequency (RF) ablation, partial surgical hepatectomy, and a sham operation
      and to inhibit HCC recurrence after RF ablation in a mouse model of spontaneously
      forming HCC in the setting of chronic inflammation (ie, the MDR2 knockout model).
      MATERIALS AND METHODS: Animal experiments were performed according to an approved
      animal care committee protocol. The authors compared the survival of MDR2
      knockout mice (an inflammation-induced HCC model) that underwent RF ablation, 35%
      partial hepatectomy (ie, left lobectomy), or a sham operation (controls) by using
      Kaplan-Meier survival curve analysis. Tumor load and tumor frequency in mice that
      underwent sham operation were further compared with those of mice treated with RF
      ablation at 1 month after therapy by using a two-tailed Student t test. Liver
      slices from mice treated with RF ablation were stained for alpha-smooth muscle
      actin and Ki-67 to establish the role of liver regeneration in the tumorigenic
      effect of RF ablation. Finally, tumor load and tumor incidence were evaluated in
      mice treated with a c-met inhibitor after RF ablation by using the Mann-Whitney U
      test. RESULTS: Ablation of 3.5% +/- 0.02 of the MDR2 knockout mice liver induced
      increased tumor load (P = .007) and reduced survival (P = .03) in comparison to
      that of controls, with no significant difference to the 10-fold volume removal of
      partial hepatectomy. Seven days after RF treatment, the border zone of the
      coagulation zone was surrounded by alpha-smooth muscle actin-positive activated
      myofibroblasts. A significant elevation of hepatocyte proliferation was also seen
      7 days after RF ablation in the distant liver (ablated lobe: P = .003; untreated
      lobe: P = .02). A c-met inhibitor significantly attenuated HCC development in
      MDR2 knockout mice treated with RF ablation (P = .001). CONCLUSION: Liver
      regeneration induced by RF ablation facilitates c-met/hepatocyte growth factor
      axis-dependent HCC tumor formation after treatment in the MDR2 knockout model.
      Blockage of the c-met/hepatocyte growth factor axis attenuates HCC recurrence,
      raising the potential for therapeutic intervention to reverse this potentially
      deleterious tumorigenic effect.

PMID- 26203710
TI  - Volumetric Cortical Bone Porosity Assessment with MR Imaging: Validation and
      Clinical Feasibility.
AB  - PURPOSE: To develop a method to assess volumetric cortical bone porosity in
      clinically practical acquisition times by measuring the signal decay at only two
      echo times (TEs) as part of a single three-dimensional ultrashort TE (UTE)
      magnetic resonance (MR) examination. MATERIALS AND METHODS: The study was
      approved by the institutional review board and complied with HIPAA guidelines.
      Written informed consent was obtained from all subjects. A marker of cortical
      bone porosity called porosity index was defined as the ratio of UTE image
      intensities at a long and short TE, and the results were compared with
      biexponential analysis. Porosity index of midtibia cortical bone samples obtained
      from 16 donors was compared with ground-truth porosity by using micro-computed
      tomographic (CT) imaging and bone mineral density by peripheral quantitative CT
      scanner. Reproducibility of porosity index were tested in volunteers, and
      clinical feasibility was evaluated in postmenopausal women. Interparameter
      associations were assessed by using Pearson or Spearman correlation coefficient.
      RESULTS: Bone specimen porosity index was correlated with micro-CT imaging
      porosity (R(2) = 0.79) and pore size (R(2) = 0.81); age (R(2) = 0.64); peripheral
      quantitative CT scanner density (R(2) = 0.49, negatively); and pore water
      fraction (R(2) = 0.62) and T2* (R(2) = 0.64) by biexponential analysis. The
      reproducibility study yielded a coefficient of variation of 2.2% and intraclass
      correlation coefficient of 0.97. The study that involved postmenopausal women
      showed a wide range of porosity index (15%-38%). CONCLUSION: A two-point MR
      imaging method to assess cortical bone porosity in humans was conceived and
      validated. This approach has the potential for clinical use to assess changes in
      cortical bone porosity that result from disease or in response to therapy. ((c))
      RSNA, 2015 Online supplemental material is available for this article.

PMID- 26203712
TI  - Case 220: Neurocutaneous Melanosis.
AB  - History A 3-month-old boy presented with new onset of seizure that subsided when
      he arrived at our institution. There was no reported fever or family history of
      seizure. Physical examination did not reveal any neurologic abnormalities.
      Multiple skin lesions of varying sizes were identified on the scalp, trunk, and
      extremities and were reported to have been present since birth. Laboratory test
      results were normal. Magnetic resonance (MR) imaging of the brain was performed. 

PMID- 26203713
TI  - High-Risk Lesions Detected at Second-Look US for Breast Lesions Identified at MR
      Imaging.

PMID- 26203714
TI  - High T1 Signal Intensity in Dentate Nucleus after Multiple Injections of Linear
      Gadolinium Chelates.

PMID- 26203715
TI  - Correlation Does Not Mean Agreement: Why Is It Still Used as a Synonym of
      Agreement?

PMID- 26203716
TI  - Stent-assisted Coil Placement for the Treatment of 211 Acutely Ruptured Wide
      necked Intracranial Aneurysms: A Single-Center 11-Year Experience.

PMID- 26203717
TI  - Prognostic Value of Cervical Nodal Necrosis in Nasopharyngeal Carcinoma: Analysis
      of 1800 Patients with Positive Cervical Nodal Metastasis at MR Imaging.

PMID- 26203718
TI  - Ronald Graham Grainger, MD, FRCP, FRCR.

PMID- 26203722
TI  - Cortical encoding of speech acoustics: Effects of noise and amplification.
AB  - OBJECTIVE: To investigate speech stimuli and background-noise-dependent changes
      in cortical auditory-evoked potentials (CAEPs) in unaided and aided conditions,
      and determine amplification effects on CAEPs. DESIGN: CAEPs to naturally produced
      syllables in quiet and in multi-talker babble were recorded, with and without a
      hearing aid in the right ear. At least 300 artifact-free trials for each
      participant were required to measure latencies and amplitudes of CAEPs. Acoustic
      characteristics of the hearing-aid-transduced stimuli were measured using in-the
      canal probe microphone measurements to determine unaided versus aided SNR and to
      compare stimulus acoustic characteristics to CAEP findings. STUDY SAMPLE: Ten
      participants with normal hearing, aged 19 to 35 years. RESULTS: CAEP latencies
      and amplitudes showed significant effects of speech contrast, background noise,
      and amplification. N1 and P2 components varied differently across conditions. In
      general, cortical processing in noise was influenced by SNR and the spectrum of
      the speech stimuli. Hearing-aid-induced spectral and temporal changes to the
      speech stimuli affected P1-N1-P2 components. Amplification produced complex
      effects on latencies and amplitudes across speech stimuli and CAEP components,
      and for quiet versus noise conditions. CONCLUSION: CAEP components reflect
      spectral and temporal characteristics of speech stimuli and acoustic changes
      induced by background noise and amplification.

PMID- 26203723
TI  - Single Incision Laparoscopic Colorectal Surgery Using Conventional Laparoscopic
      Instruments: Initial Experience with 44 Cases.
AB  - BACKGROUND: We aimed to retrospectively investigate the short-term outcome,
      technical feasibility, and safety of single incision transumbilical laparoscopic
      colorectal surgery (SITULCS) using conventional laparoscopic surgical
      instruments. METHODS: From April 2009 to July 2012, 44 patients with colorectal
      tumors underwent SITULCS at our department by using conventional laparoscopic
      instruments. The operations included right hemicolectomy (n = 8), sigmoidectomy
      (n = 5), total colectomy (n = 4), anterior resection of rectal cancer (n = 23),
      and abdominoperineal resection of rectal cancer (n = 4). We accessed the
      intraperitoneal lesions by three trocars through a single triangle-shaped
      umbilical incision using conventional instruments. RESULTS: We successfully
      completed SITULCS without specially designed instruments. No patient was
      converted to multiport laparoscopic surgery or open surgery. Only one case
      developed intraoperative bleeding and one postoperative adhesive intestinal
      obstruction. CONCLUSION: Our experience shows that SITULCS using conventional
      instruments is feasible, safe, and convenient.

PMID- 26203724
TI  - ?

PMID- 26203725
TI  - ?

PMID- 26203726
TI  - ?

PMID- 26203728
TI  - ?

PMID- 26203727
TI  - ?

PMID- 26203731
TI  - Uveitis attack and drug reaction due to cefuroxime axetil.
AB  - Antibiotics are natural or synthetic substances that are used to control
      bacterial infections because antibiotics are by definition only effective against
      bacteria. A 30-year-old female came to our emergency clinic complaining rubor in
      both eyes, especially in the left eye, with swelling, rubor and pain in ears, and
      eruption in lips extremities. In her anamnesis, it has been determined that she
      did not have any medical disease that requires regular utilization of drugs.
      After the patient received cefuroxime axetil for acute tonsillitis, she observed
      eruptions in lip extremities on the 3rd day, but she did not care about it. On
      the 5th day, rubor in both eyes and, especially in the left eye, have been
      developed, and complaints such as unable to look toward light and pain have
      started together with swelling, rubor, and pain in both ears. She came to our
      clinic because she was very much worried about the situation. In this study, we
      aimed to discuss a drug reaction characterized by face and ear skin observations,
      due to uveitis after the use of antibiotics including cefuroxime axetil for acute
      tonsillitis. 

PMID- 26203732
TI  - A family-specific linkage analysis of blood lipid response to fenofibrate in the
      Genetics of Lipid Lowering Drug and Diet Network.
AB  - Cost-effective identification of novel pharmacogenetic variants remains a
      pressing need in the field. Using data from the Genetics of Lipid Lowering Drugs
      and Diet Network, we identified genomic regions of relevance to fenofibrate
      response in a sample of 173 families. Our approach included a multipoint linkage
      scan, followed by selection of the families showing evidence of linkage. We
      identified a strong signal for changes in LDL-cholesterol (LDL-C) on chromosome 7
      (peak logarithm of odds score = 4.76) in the full sample (n = 821). The signal
      for LDL-C response remained even after adjusting for baseline LDL-C. Restricting
      analyses only to the families contributing to the linkage signal for LDL-C (N =
      19), we observed a peak logarithm of odds score of 5.17 for chromosome 7. Two
      genes under this peak (ABCB4 and CD36) were of biological interest. These results
      suggest that linked family analyses might be a useful approach to gene discovery
      in the presence of a complex (e.g. multigenic) phenotype.

PMID- 26203733
TI  - Hemostasis abnormalities in cirrhosis.
AB  - PURPOSE OF REVIEW: The long-lasting paradigm of cirrhosis as the epitome of the
      acquired hemorrhagic coagulopathies has been challenged by evidence from the
      literature. This article reviews the mechanisms responsible for regulation of
      hemostasis in the light of the evidence provided within the last few years.
      RECENT FINDINGS: Numerous studies have evaluated the mechanisms responsible for
      regulation of primary hemostasis, coagulation and fibrinolysis which were thought
      to be severely impaired in cirrhosis and were considered responsible for the
      abnormalities of the prothrombin time and the bleeding events observed in these
      patients. These evaluations have been performed by newer laboratory tests under
      experimental conditions that mimic closely the condition operating in vivo.
      SUMMARY: Cirrhosis presents with thrombocytopenia and decreased levels of both
      pro- and anticoagulants. Notable exceptions are factor VIII and von Willebrand
      factor (VWF) which are increased. Thrombocytopenia (unless very severe) is no
      longer considered a bleeding risk as platelets from cirrhosis display normal
      adhesiveness in a flowing system that is mainly supported by the increased levels
      of VWF. Patients with cirrhosis generate normal amounts of thrombin that is
      mainly supported by the concomitant deficiency of pro- and anticoagulants that
      restores the balance between these two opposing drivers.

PMID- 26203734
TI  - Updates in pediatric venous thromboembolism.
AB  - PURPOSE OF REVIEW: The occurrence of pediatric venous thromboembolism (VTE) and
      the associated sequelae are increasing. The purpose of this PubMed-based review
      was to summarize the evidence published between 1 August 2014 and 31 March 2015
      regarding pediatric VTE epidemiology, risk factors and risk scores, as well as
      the results from clinical prevention and treatment studies in children. We also
      sought to provide an update regarding ongoing clinical trials in pediatric VTE
      prevention and treatment, based on a recent (31 March 2015) search of the
      clinicaltrials.gov and EudraCT clinical trial registration databases. RECENT
      FINDINGS: Recent research has defined and/or substantiated risk factors and risk
      models for pediatric VTE. Studies of pharmacokinetics/pharmacodynamics and
      safety/efficacy of fondaparinux and dalteparin have also been reported, in
      addition to findings of the pilot/feasibility phase of a randomized controlled
      trial on duration of anticoagulation. With regard to oral direct anticoagulants,
      to date 14 pediatric clinical trials have been registered on clinicaltrials.gov
      and EudraCT, some of which represent US/North American instances of trials
      previously launched in Europe. SUMMARY: The present findings on published studies
      and registered trials in pediatric VTE mark an ongoing period of remarkable
      activity and advancement in the field of pediatric VTE.

PMID- 26203735
TI  - A Biomechanical Comparison of the Long Snap in Football Between High School and
      University Football Players.
AB  - Limited previous research was located that examined the technique of the long
      snap in football. The purpose of the study was to compare the joint movements,
      joint velocities, and body positions used to perform fast and accurate long snaps
      in high school (HS) and university (UNI) athletes. Ten HS and 10 UNI subjects
      were recruited for filming, each performing 10 snaps at a target with the fastest
      and most accurate trial being selected for subject analysis. Eighty-three
      variables were measured using Dartfish Team Pro 4.5.2 video analysis software,
      with statistical analysis performed using Microsoft Excel and SPSS 16.0. Several
      significant comparisons to long snapping technique between groups were noted
      during analysis; however, the body position and movement variables at release
      showed the greatest number of significant differences. The UNI athletes
      demonstrated significantly higher release velocity and left elbow extension
      velocity, with significantly lower release height and release angle than the HS
      group. Total snap time (release time + total flight time) was determined to have
      the strongest correlation to release velocity for the HS group (r = -0.915) and
      UNI group (r = -0.918). The study suggests HS long snappers may benefit from less
      elbow flexion and more knee flexion in the backswing (set position) to increase
      release velocity. University long snappers may benefit from increased left elbow
      extension range of motion during force production and decreased shoulder flexion
      at critical instant to increase long snap release velocity.

PMID- 26203736
TI  - Short-term Resistance and Plyometric Training Improves Eccentric Phase Kinetics
      in Jumping.
AB  - The purpose of this investigation was to examine the effect of an abbreviated
      resistance and plyometric training program on force- and power-time curve
      variables during jumping. Nineteen male subjects were assigned to either a
      training (n = 9) or control group (n = 10). Training consisted of performing 3
      sets of 3 repetition squats (90% of 1 repetition maximum [RM]) and 5 sets of 6
      repetition drop jumps from 40 cm twice per week for 4 weeks. A 1RM in the squat
      and countermovement (CMJ) and static jump (SJ) performance was assessed before
      and after training. Several variables were analyzed for individual subject force-
      and power-time curves for the jumps. Average force- and power-time curves for all
      subjects combined were also analyzed. Absolute and relative squat strength
      significantly increased in training group (p <= 0.05). Calculation of variables
      from individual subject force-time curves during the CMJ indicated a significant
      decrease in eccentric time, minimum force, and eccentric impulse and significant
      increase in eccentric rate of force development in training group. Analysis of
      individual power-time curves in the CMJ also revealed a significant decrease in
      minimum power and eccentric work and a significant increase in eccentric rate of
      power development. No significant changes occurred in the variables measured for
      the SJ. The results of this study indicate that short-term strength and
      plyometric training may preferentially influence eccentric performance variables
      during jumping in comparison with longer term training enhancements to the
      concentric phase performance.

PMID- 26203737
TI  - High-Intensity Cycling Training: The Effect of Work-to-Rest Intervals on Running
      Performance Measures.
AB  - The work-to-rest ratio during cycling-based high-intensity interval training
      (HIT) could be important in regulating physiological and performance adaptations.
      We sought to determine the effectiveness of cycling-based HIT with different work
      to-rest ratios for long-distance running. Thirty-two long-distance runners (age:
      39 +/- 8 years; sex: 14 men, 18 women; average weekly running training volume: 25
      miles) underwent baseline testing (3-km time-trial, V[Combining Dot Above]O2peak
      and time to exhaustion, and Wingate test) before a 2-week matched-work cycling
      HIT of 6 * 10-second sprints with different rest periods (30 seconds [R30], 80
      seconds [R80], 120 seconds [R120], or control). Three-kilometer time trial was
      significantly improved in the R30 group only (3.1 +/- 4.0%, p = 0.04), whereas
      time to exhaustion was significantly increased in the 2 groups with a lower work
      to-rest ratio (R30 group 6.4 +/- 6.3%, p = 0.003 vs. R80 group 4.4 +/- 2.7%, p =
      0.03 vs. R120 group 1.9 +/- 5.0%, p = 0.2). However, improvements in average
      power production were significantly greater with a higher work-to-rest ratio (R30
      group 0.3 +/- 4.1%, p = 0.8 vs. R80 group 4.6 +/- 4.2%, p = 0.03 vs. R120 group
      5.3 +/- 5.9%, p = 0.02), whereas peak power significantly increased only in the
      R80 group (8.5 +/- 8.2%, p = 0.04) but not in the R30 group (4.3 +/- 6.1%, p =
      0.3) or in the R120 group (7.1 +/- 7.9%, p = 0.09). Therefore, cycling-based HIT
      is an effective way to improve running performance, and the type and magnitude of
      adaptation is dependent on the work-to-rest ratio.

PMID- 26203738
TI  - Fingerboard in Competitive Bouldering: Training Effects on Grip Strength and
      Endurance.
AB  - Bouldering (BL) is an independent discipline of sport climbing, with grip
      strength and endurance as key factors. Although the sport has grown increasingly
      popular and competitive, limited research has been conducted on commonly used
      training methods to maximize BL performance. The purpose of this study was to
      investigate the training effects of 4 weeks of fingerboarding (FB) on grip
      strength and endurance in competitive BL. Twenty-three highly advanced male
      boulderers (25.6 +/- 4.4 y; 1.78 +/- 0.05 m; 70.1 +/- 5.4 kg; 6.2 +/- 2.8 y
      climbing; 7b+ Fb mean ability) were randomly allocated to a 4-week FB (n = 11) or
      BL (n = 12) training regimen. Pretests and posttests (50-min duration) involved
      (a) handheld dynamometry (GS) to assess grip strength, (b) dead hangs (DH), and
      (c) intermittent finger hangs (IFH) to assess grip endurance. After the 4-week
      regimen, GS increased significantly in the FB group (2.5 +/- 1.4 kg, p < 0.001)
      but not in the BL group (1.4 +/- 2.8 kg, p = 0.109). The mean increase in DH
      ranged from 5.4 to 6.7 seconds in the FB group and was significantly (p <= 0.05)
      higher than that in the BL group (3.0-3.9 seconds). Finally, significantly higher
      IFH gains were observed in the FB group (p = 0.004), with a mean gain of 26
      seconds, but not in the BL group (p = 0.168). These results suggest that FB is
      highly effective in increasing grip strength and endurance in competitive BL.

PMID- 26203739
TI  - Performance Comparison of Student-Athletes and General College Students on the
      Functional Movement Screen and the Y Balance Test.
AB  - Although various studies have assessed performance of athletes on the Functional
      Movement Screen (FMS) and the Y Balance Test (YBT), no study to date has directly
      evaluated a comparison of performance between athletes and members of the general
      population. Thus, to better understand the application of the FMS and the YBT to
      general college students, this study examined whether or not general college
      students performed similarly to student-athletes on the FMS (composite and
      movement pattern scores) and the YBT (composite and reach directions). This study
      evaluated 167 Division I student-athletes and 103 general college students from
      the same university on the FMS and the YBT. No difference was found in FMS
      composite scores between student-athletes and general college students. For FMS
      movement patterns, female student-athletes scored higher than general college
      students in the deep squat. No difference was found for men in any FMS movement
      pattern. Female student-athletes scored higher than female general college
      students in YBT composite scores; no difference was found for men in YBT
      composite scores. In analysis of YBT reach directions, female student-athletes
      scored higher than female general college students in all reach directions,
      whereas no difference was found in men. Existing research on the FMS composite
      score in athletic populations may apply to a general college population for the
      purposes of preparticipation screening, injury prediction, etc. Existing research
      on the YBT in male athletic populations is expected to apply equally to general
      college males for the purposes of preparticipation screening, injury prediction,
      etc.

PMID- 26203740
TI  - An Examination of Fatigue Index and Velocity-Related Force Loss for the Forearm
      Flexors.
AB  - The purpose of this study was to examine the relationship between the fatigue
      index from an isokinetic fatigue test and the velocity-related decrease in peak
      torque for the forearm flexors. After a familiarization session, 13 habitually
      active males (mean +/- SD, age = 23.8 +/- 3.1 years) reported to the laboratory
      to perform either 50 repeated, maximal, concentric isokinetic muscle actions of
      the dominant forearm flexors at a velocity of 180 degrees .s(-1) or 6 separate
      sets of 3 maximal concentric isokinetic muscle actions at randomly ordered
      velocities of 30, 90, 150, 270, and 330 degrees .s(-1). The correlation between
      the relative percent declines in peak torque during the 2 isokinetic tests was
      then examined. The results indicated an inverse relationship (r = -0.75, p <
      0.01) between these 2 variables. That is, the subjects who demonstrated the
      greatest fatigue indexes (i.e., those who were most susceptible to fatigue) were
      generally the most resistant to a velocity-related torque loss. These findings
      support the possibility of using a multiple-velocity isokinetic test to estimate
      fiber type composition, just as fatigue-based tests have been used.

PMID- 26203741
TI  - Relationship of Physical Fitness Measures vs. Occupational Physical Ability in
      Campus Law Enforcement Officers.
AB  - Law enforcement officers (LEOs) on university campuses are required to perform a
      variety of physical occupational tasks. Identifying which physical fitness
      characteristics are associated with these occupational tasks will assist in the
      development of appropriate exercise programs and physical fitness assessments.
      Therefore, the purpose of this study was to identify physical fitness and
      demographic characteristics that were correlated with occupational tasks commonly
      performed by campus LEOs. The occupational assessment was conducted using an
      Officer Physical Ability Test (OPAT), which simulated a foot chase of a suspect.
      Sixteen male LEOs (age: 33.1 +/- 8.7 years; body mass: 87.2 +/- 11.2 kg; height:
      179.0 +/- 7.9 cm) performed the OPAT. A battery of physical fitness tests were
      used to assess aerobic capacity, muscular endurance, strength, power,
      flexibility, agility, and body composition. Bivariate correlations were performed
      to identify significant (p <= 0.05) correlations between physical fitness
      characteristics and OPAT time. The officers' age was significantly correlated to
      the majority of OPAT tasks, physical fitness, and anthropometric assessments.
      Therefore, partial correlations were used to control for the confounding effects
      of age. After controlling for the officers' age, the overall OPAT time was
      significantly correlated with agility (r = 0.57) and aerobic endurance (r = 
      0.65). Furthermore, push-up, curl-up, body mass, waist circumference, and
      abdominal circumference were significantly correlated to individual OPAT tasks.
      In conclusion, exercise programs and fitness assessments should be used for
      campus LEOs that address a variety of physical fitness characteristics associated
      with occupational performance. In addition, exercise programs should focus on
      body composition management and fitness for older LEOs.

PMID- 26203742
TI  - Comparison of Anterior Segment Measurements With a Dual Scheimpflug Placido
      Corneal Topographer and a New Partial Coherence Interferometer in Keratoconic
      Eyes.
AB  - PURPOSE: To evaluate the repeatability and agreement of the anterior segment
      measurements obtained using the Galilei dual Scheimpflug analyzer (Galilei DSA;
      Ziemer) and Nidek AL Scan (Nidek CO, Aichi, Japan) biometry in keratoconic and
      normal eyes. METHODS: Three consecutive measurements were performed by the same
      examiner using both devices in 62 healthy and 88 keratoconic eyes. Central
      corneal thickness (CCT), anterior chamber depth, keratometry readings (K) [in
      flattest meridian (Kf), in steepest meridian (Ks), and mean (Km)], and white-to
      white distance were evaluated. Repeatability was assessed by calculating the
      within-subject SD and coefficient of variation. The agreement between both
      devices was assessed using the Bland-Altman method. RESULTS: Both devices
      achieved excellent repeatability for all parameters in each group. The 95% limits
      of agreement (LoA) between both devices were also very narrow and acceptable for
      all parameters in normal corneas. However, the 95% LoA for agreement was large
      for CCT and measurements related to K (Kf, Ks, and Km) using both 2.4 and 3.3 mm
      in keratoconic eyes. In addition, compared with the Galilei DSA, K values of the
      Nidek AL Scan using a diameter of 3.3 mm showed slightly closer 95% LoA than
      those obtained using a diameter of 2.4 mm. CONCLUSIONS: In normal eyes, the
      Galilei DSA and Nidek AL Scan can be used interchangeably for anterior segment
      measurements. In keratoconic eyes, both devices yielded interchangeable anterior
      chamber depth and white-to-white distance measurements, whereas CCT and
      keratometry measurements showed clinically significant differences.

PMID- 26203744
TI  - Descemet Stripping Endothelial Keratoplasty in Iridocorneal Endothelial Syndrome:
      Postoperative Complications and Long-Term Outcomes.
AB  - PURPOSE: To determine the long-term outcomes of Descemet stripping endothelial
      keratoplasty (DSEK) in iridocorneal endothelial (ICE) syndrome. METHODS:
      Retrospective review of a consecutive series of 4 eyes of 4 patients with ICE
      syndrome treated by DSEK surgery at a single institution with follow-up between 2
      and 7 years. RESULTS: Mean follow-up after initial DSEK surgery was 55 months
      (range, 24-95 months). One eye required 1 repeat DSEK, and 2 eyes required 2
      repeat DSEKs for a total of 9 DSEK operations across the 4 eyes. There were no
      graft dislocations and no primary graft failures. Seven of 9 grafts achieved a
      visual acuity of 6/12 or better by 6 months. Mean endothelial cell loss at 3, 6,
      12, and 24 months was 55 +/- 14%, 78 +/- 5%, 80 +/- 6%, and 83 +/- 9%,
      respectively. Long-term graft survival was poor with 7 of 9 grafts suffering late
      endothelial failure by a mean of 18 +/- 7 months (range, 12-28 months). Mean
      graft survival on Kaplan-Meier analysis was 19 months (95% confidence interval,
      14-24 months). CONCLUSIONS: DSEK has the potential to provide good short-term
      visual outcomes in eyes with ICE syndrome. However, long-term graft survival
      beyond 2 years is poor because of late endothelial failure. Patients with ICE
      considering DSEK surgery should be warned about the high probability of repeat
      surgery.

PMID- 26203743
TI  - Visual Recovery and Endothelial Cell Survival After Descemet Stripping Automated
      Endothelial Keratoplasty for Failed Penetrating Keratoplasty Grafts-A Cohort
      Study.
AB  - PURPOSE: To assess visual recovery and donor cell survival after Descemet
      stripping automated endothelial keratoplasty (DSAEK) for the repair of failed
      penetrating keratoplasty (PK) grafts. METHODS: Best spectacle-corrected Snellen
      visual acuity results after DSAEK were compared with best-ever documented visual
      acuity (BDVA) results obtained with the previous PK graft in a prospective cohort
      study. Donor cell survival after DSAEK for PK repair was compared with cell
      survival after DSAEK for Fuchs endothelial dystrophy and pseudophakic bullous
      keratopathy. Differences in the logMAR best spectacle-corrected Snellen visual
      acuity and endothelial cell loss rates were calculated. RESULTS: Twenty-eight
      eyes with DSAEK for PK repair were identified, 21 of which lacked vision-limiting
      comorbidities. The mean follow-up was 18.4 +/- 10.6 months. At 3 months
      postoperatively, 10/21 eyes (48%) regained their BDVA. By 24 months, only 14%
      remained with 0.2 logMAR below their BDVA. Endothelial cell counts decreased
      significantly faster in patients with DSAEK for failed PK (P = 0.024) or
      pseudophakic bullous keratopathy (P = 0.018) than in patients with DSAEK for
      Fuchs endothelial dystrophy. CONCLUSIONS: DSAEK for the restoration of failed PK
      grafts promotes rapid visual recovery within the visual limits of the previous PK
      graft. Increased endothelial cell loss is noted relative to other DSAEK
      indications, which may result in earlier endothelial graft failure in renovated
      PK.

PMID- 26203745
TI  - Effects of Quercetin in a Mouse Model of Experimental Dry Eye.
AB  - PURPOSE: To evaluate the effect of treatment with quercetin in a mouse model of
      dry eye. METHODS: 0.5% quercetin eye drops were prepared and an experimental dry
      eye model was induced in NOD.B10.H2(b) mice through desiccation stress. The mice
      were divided into 3 groups according to the treatment regimen: the DS 10D group
      (desiccation stress for 10 days), the phosphate buffered saline (PBS) group, and
      the quercetin group. Tear volumes and corneal irregularity scores were measured
      at 3, 5, 7, and 10 days after treatment. Hematoxylin and eosin staining, periodic
      acid-Schiff staining, and immunohistochemistry were performed at the end of the
      experiment. RESULTS: The quercetin group had increased tear volumes (0.2 +/- 0.03
      MUm, P < 0.05) and decreased corneal irregularity scores (0.7 +/- 0.6, P < 0.05)
      compared with those of the PBS group. On histological examination, the quercetin
      group exhibited restored smooth corneal surfaces without detaching corneal
      epithelial cells and had significantly increased goblet cell density (13.8 +/-
      0.8 cells/0.1 mm2, P < 0.05) compared with the PBS group. The quercetin group
      also exhibited significant declines of MMP-2 (5.1-fold of control, P < 0.01), MMP
      9 (2.5-fold of control, P < 0.01), ICAM-1 (2.2-fold of control, P < 0.01), and
      VCAM-1 (2.3-fold of control, P < 0.01) levels in the lacrimal gland than did the
      PBS group. CONCLUSIONS: Topical application of quercetin can help to improve
      ocular surface disorders of dry eye not only by decreasing the corneal surface
      irregularity but also by increasing the tear volume and goblet cell density.
      Moreover, quercetin has the potential for use in eye drops as a treatment for dry
      eye disease with antiinflammatory effects on the lacrimal functional unit.

PMID- 26203746
TI  - Long-Term Outcomes of Epithelial Debridement and Diamond Burr Polishing for
      Corneal Epithelial Irregularity and Recurrent Corneal Erosion.
AB  - PURPOSE: To determine the efficacy of epithelial debridement and diamond burr
      polishing (ED + DBP) in managing recurrent corneal erosion (RCE) and visually
      significant epithelial irregularity associated with epithelial basement membrane
      dystrophy (VS-EBMD). METHODS: Retrospective, interventional, consecutive case
      series of all ED + DBP procedures performed between December 1, 2002, and
      December 1, 2014. RESULTS: ED + DBP was performed in 91 eyes (66 patients) for
      the management of RCE and VS-EBMD. Sixty percent (55/91) of the procedures were
      performed for RCE, of which 65% (36/55) were associated with EBMD and 22% (12/55)
      with previous corneal trauma. Forty-six percent (42/91) of the procedures were
      performed for VS-EBMD, including 6 eyes with RCE. RCE resolved after treatment in
      97% of eyes with >3 months of follow-up (mean, 33.2 months; range, 3.5-137.6
      months). Corrected distance visual acuity (CDVA) and mean topographic astigmatism
      improved significantly in the 36 eyes treated for VS-EBMD with >1 month of follow
      up. In none of the 22 eyes treated for VS-EBMD with >3 months of follow-up did
      EBMD recur (mean, 31.7 months; range, 3.2-137.6 months). Surgically induced
      subepithelial haze was present on last follow-up in 9.4% (8/85) of eyes with >1
      month of follow-up, but was not associated with decreased final CDVA in any
      patient. CONCLUSIONS: ED + DBP is effective in producing long-term resolution of
      RCE in 95% of treated eyes and significant improvement in CDVA, decreased
      topographic astigmatism, and long-term resolution of VS-EBMD in 100% of treated
      eyes.

PMID- 26203747
TI  - Coefficient of Friction of Human Corneal Tissue.
AB  - PURPOSE: A novel property evaluation methodology was used to determine the
      elusive value for the human corneal coefficient of friction (CoF). METHODS: Using
      a microtribometer on 28 fresh human donor corneas with intact epithelia, the CoF
      was determined in 4 test solutions (>=5 corneas/solution): tear-mimicking
      solution (TMS) in borate-buffered saline (TMS-PS), TMS in phosphate-buffered
      saline (TMS-PBS), TMS with HEPES-buffered saline (TMS-HEPES), and tear-like fluid
      in PBS (TLF-PBS). RESULTS: Mean (SD) CoF values ranged from 0.006 to 0.015 and
      were 0.013 (0.010) in TMS-PS, 0.006 (0.003) in TMS-PBS, 0.014 (0.005) in TMS
      HEPES, and 0.015 (0.009) in TLF-PBS. Statistically significant differences were
      shown for TMS-PBS versus TLF (P = 0.0424) and TMS-PBS versus TMS-HEPES (P =
      0.0179), but not for TMS-PBS versus TMS-PS (P = 0.2389). CONCLUSIONS: Successful
      measurement of the fresh human corneal tissue CoF was demonstrated, with values
      differing in the evaluated buffer solutions, within this limited sample size.

PMID- 26203748
TI  - Investigation of the Role of Bacteria in the Development of Acanthamoeba
      Keratitis.
AB  - PURPOSE: Recently, much interest has been shown in bacteria extracted from
      Acanthamoeba strains isolated from patients with Acanthamoeba keratitis (AK). We
      hypothesized that the bacteria in Acanthamoeba strains may be a contributing
      factor in the development of AK. To prove this hypothesis, we investigated the
      involvement of bacteria harbored by Acanthamoeba in causing progressive ocular
      infection in rabbit corneas. METHODS: One Acanthamoeba strain (T4 genotype) that
      harbored bacteria was isolated from a patient with AK. The Acanthamoeba strain
      pretreated or not pretreated with levofloxacin (LVFX) was inoculated into rabbit
      corneas. We also tested the effect of LVFX eye drops on keratitis induced by the
      Acanthamoeba strain. The infected rabbit eyes were evaluated for clinical scores,
      Acanthamoeba 18S rDNA and bacterial 16S rDNA numbers were analyzed by the real
      time polymerase chain reaction, and the presence of Acanthamoeba was analyzed by
      histological examination. RESULTS: Inoculation of nonpretreated Acanthamoeba
      resulted in severe keratitis. In contrast, inoculation of LVFX-pretreated
      Acanthamoeba did not induce keratitis (mean clinical score, 17.3 vs. 2.3; P <
      0.05). Rabbit corneas inoculated with nonpretreated Acanthamoeba followed by
      topical LVFX therapy developed severe keratitis. In corneas inoculated with
      nonpretreated Acanthamoeba followed by LVFX therapy, the number of Acanthamoeba
      18S rDNA copies was significantly higher than in other groups (P < 0.05), whereas
      the bacterial 16S rDNA gene was undetectable. Acanthamoeba cysts were detected by
      Fungiflora Y staining only in corneas inoculated with nonpretreated Acanthamoeba
      followed by LVFX therapy. CONCLUSIONS: These results suggest that the presence of
      bacteria in Acanthamoeba may be required for the development of AK.

PMID- 26203749
TI  - Keratoconus Clinical Findings According to Different Classifications.
AB  - PURPOSE: To demonstrate the topographic and keratometric findings in patients
      with keratoconus (KC), according to age, sex, and KC severity groups. METHODS: A
      total of 2073 eyes of 1081 patients with KC were consecutively diagnosed and
      enrolled in this prospective cross-sectional study. All patients underwent
      ophthalmic examination and Pentacam (Oculus Optikgerate GmbH) measurements. The
      patients were divided into different groups according to their age, sex, Amsler
      Krumeich classification, and keratoconus severity score classification.
      Keratometric (K) values (flattest, steepest, and mean), central and thinnest
      corneal thickness, and manifest refraction were recorded for each patient with KC
      and they were then compared according to the patient's age, sex, and KC severity
      groups. RESULTS: The age (mean +/- SD) of the population was 24 +/- 7 years. The
      average central corneal thickness and mean K of all patients were 462 +/- 45 MUm
      and 48.8 +/- 4.8 diopters, respectively. Female patients with KC were
      significantly younger and had significantly higher K values and lower anterior
      chamber depth than those of men. All parameters except for the pupil diameter and
      astigmatism were significantly associated with KC severity grades. The thinnest
      corneal thickness was the most important and also the most sensitive and specific
      parameter for distinguishing all stages of KC severity in all KC severity
      classifications. The Amsler-Krumeich classification had the most correlation with
      other severity classifications. CONCLUSIONS: The results of this study enable
      clinicians and researchers to understand better the differences between clinical
      characteristics between sex, age groups, and the changes in clinical
      characteristics during disease progression, which may lead to further advancement
      in KC management.

PMID- 26203750
TI  - Combined Excimer Laser Photoablation and Amniotic Membrane Overlay for Relief of
      Symptomatic Discomfort in Gelatinous Drop-like Corneal Dystrophy.
AB  - PURPOSE: To describe the efficacy of combined excimer laser photoablation and
      amniotic overlay membrane in the relief of symptomatic discomfort in a 17-year
      old patient who had gelatinous drop-like corneal dystrophy. METHODS: The best
      corrected visual acuity (BCVA) was measured with Snellen letters. Slit-lamp
      examination of the ocular surface and anterior chamber was performed at baseline.
      Results were photodocumented. Excimer laser photoablation was performed and
      subsequently 2 amniotic membranes were transconjunctivally fixated with 10.0
      nylon sutures. Investigations and documentation were performed at baseline, every
      2 months in the first year, and then every 6 months. The duration of follow-up
      was 22 months. RESULTS: At baseline, the BCVA was 20/70 in the right eye and
      20/200 in the left eye. The patient reported distinct photophobia. Slit-lamp
      examination was difficult because of blepharospasm. Although gelatinous drops
      developed again and the BCVA decreased to 2/200, the patient reported significant
      relief after both microsurgical treatments and remained comfortable at 20 and 22
      months. CONCLUSIONS: Excimer laser photocoagulation combined with amniotic
      membrane overlay does not stop the development of gelatinous drop-like corneal
      dystrophy but may improve subjective comfort. Such treatment does not hinder
      subsequent lamellar or penetrating grafts and is helpful in providing the
      necessary time for preparation of matched keratoplasties.

PMID- 26203751
TI  - Red Reflex-Guided Big-Bubble Deep Anterior Lamellar Keratoplasty: A Simple
      Technique to Judge Dissection Depth.
AB  - PURPOSE: To report the results of a modified big-bubble deep anterior lamellar
      keratoplasty technique using the intraoperative red reflex to visualize the
      amount of residual stroma beneath the inserted cannula. METHODS: A total of 132
      consecutive keratoconic eyes were included in this retrospective, noncomparative,
      interventional case series. Before starting surgery, pharmacologic mydriasis was
      induced in all eyes undergoing a big-bubble deep anterior lamellar keratoplasty
      procedure. After partial trephination of the recipient cornea, a spatula was
      inserted at the base of the incision and advanced into depth using as a reference
      the thin dark line seen in the red reflex ahead of the advancing tip; the stromal
      depth reached was measured using anterior segment optical coherence tomography.
      Finally, the spatula was exchanged for a 27-gauge cannula, and air was injected
      to create a big bubble. The stromal depth reached with the spatula, success rate
      of big-bubble formation, and complications were recorded. RESULTS: The big bubble
      was obtained in 118 of 132 eyes (89.4%). Of the remaining 14 eyes, 11 underwent
      completion of the procedure by manual dissection and 3 were converted to
      penetrating keratoplasty because the bubble burst while trying to enlarge it.
      Perforation did not occur in any case during cannula insertion. The average
      thickness reached with the stromal dissection was 64.3 +/- 19.5 MUm. CONCLUSIONS:
      The thin dark line, seen in the red reflex obtained with pharmacologic dilation,
      provides a useful and effective reference that can be used to visualize and judge
      the depth of dissection, thus allowing a safer and reproducible approach to the
      pre-Descemetic stroma.

PMID- 26203752
TI  - Uneven Meibomian Gland Dropout Over the Tarsal Plate and its Correlation With
      Meibomian Gland Dysfunction.
AB  - PURPOSE: To evaluate the distribution of meibomian gland dropout and analyze the
      correlation between dropout and meibomian gland dysfunction (MGD). METHODS: A
      total of 161 eyes of 85 patients with MGD were recruited as the MGD group; 88
      eyes of 46 health volunteers were enrolled as the control group (2:1 matched for
      age and sex). Examinations included the Schirmer I test, breakup time, symptom
      questionnaire, corneal fluorescein staining, meibum quality, meibomian gland
      expressibility, and meibomian gland dropout. RESULTS: (1) The incidences of
      chalazion and eyelid surgery were significantly higher in patients with MGD. (2)
      All clinical indexes were better in healthy volunteers (all P < 0.05). (3) The
      dropout in the upper eyelid was statistically lower (P < 0.01) in both groups.
      The nasal and/or temporal part had higher dropout than did the middle part,
      except in the lower eyelid of the control group. (4) The entire or partial
      dropout was positively related to MGD occurrence. Both additive dropout of the
      entire 2 eyelids and that of the 2 nasal parts had the strongest correlation (r =
      0.792, P < 0.01). (5) In the MGD group, breakup time was most negatively related
      to upper nasal dropout (r = -0.229, P < 0.05). The corneal staining score was
      positively related only to the dropout of additive (r = 0.185, P < 0.05) and
      lower (r = 0.258, P < 0.05) middle parts. CONCLUSIONS: (1) Uneven dropouts exist
      in different or single eyelids. (2) Dropout evaluation is better when covering
      the entire area of both upper and lower meibomians. (3) Nasal part dropout plays
      a more essential role than the other dropouts in MGD occurrence.

PMID- 26203753
TI  - Association Between Meibomian Gland Testing and Ocular Surface Sensitivity.
AB  - PURPOSE: To assess whether corneal sensitivity is associated with clinical tests
      assessing the tear film and meibomian glands. METHODS: Subjects were recruited
      based on the history of contact lens wear and the extent of meibomian gland
      dropout. Clinical examination included assessment of symptoms, redness of the
      lower eyelid margin, lipid layer thickness, esthesiometry of the inferior cornea
      and palpebral conjunctiva, noninvasive tear breakup time, Schirmer test
      assessment, and meibomian gland assessment through orifice count and expressed
      meibum quality grade. Subjects were grouped into a high corneal sensitivity (HS)
      group or low corneal sensitivity (LS) group, based on the median sensitivity
      measure. Groups for palpebral conjunctival sensitivity were created in the same
      manner. Mann-Whitney U tests were used for comparisons of sensitivity groups, and
      a Spearman rho correlation coefficient was used to study the associations between
      each tear film characteristic and the sensitivities. RESULTS: Fifty-seven
      subjects with an average age of 34.7 years (SD = 15.1) were included in the
      analysis, of which 63.2% were female. The median corneal and conjunctival
      thresholds for sensation were 0.5 and 1.4 g/mm, respectively. The average
      noninvasive tear breakup time [HS: 7.8 seconds [interquartile range (IQR) = 5.7];
      LS: 11.6 seconds (IQR = 8.4); P = 0.05] and Schirmer test assessments [HS: 16.0
      mm (IQR = 15.0); LS: 25.0 mm (IQR = 19.0); P = 0.04] were significantly different
      between the palpebral conjunctival HS and LS groups. All other group comparisons
      and correlations were not statistically significant. CONCLUSIONS: The palpebral
      conjunctival sensitivity may be more critical than the corneal sensitivity when
      assessing dry eye.

PMID- 26203754
TI  - Physical and Biological Characterization of the Gamma-Irradiated Human Cornea.
AB  - PURPOSE: To compare the physical and biological characteristics of commercial
      gamma-irradiated corneas with those of fresh human corneas and to determine
      suitability for transplantation. METHODS: The physical properties of gamma
      irradiated and fresh corneas were evaluated with respect to light transmittance,
      hydration (swelling ratio), elastic modulus (compressive modulus by the
      indentation method), matrix organization (differential scanning calorimetry), and
      morphology (light and transmission electron microscopy). The biological
      properties of the gamma-irradiated cornea, including residual cell content and
      cellular biocompatibility, were evaluated by quantifying DNA content and
      measuring the proliferation rate of human corneal epithelial cells, respectively.
      RESULTS: The hydration, light transmittance, elastic modulus, and proliferation
      rate of human corneal epithelial cells were not significantly different between
      fresh and gamma-irradiated corneas. However, differences were observed in tissue
      morphology, DNA content, and thermal properties. The density of collagen fibrils
      of the gamma-irradiated corneal sample (160.6 +/- 33.2 fibrils/MUm) was
      significantly lower than that of the fresh corneal sample (310.0 +/- 44.7
      fibrils/MUm). Additionally, in the gamma-irradiated corneas, cell fragments-but
      not viable cells-were observed, supported by lower DNA content of the gamma
      irradiated cornea (1.0 +/- 0.1 MUg/mg) than in fresh corneas (1.9 MUg/mg).
      Moreover, the denaturation temperature of gamma-irradiated corneas (61.8 +/- 1.1 
      degrees C) was significantly lower than that of fresh corneas (66.1 +/- 1.9 
      degrees C). CONCLUSIONS: Despite structural changes due to irradiation, the
      physical and biological properties of the gamma-irradiated cornea remain similar
      to the fresh cornea. These factors, combined with a decreased risk of rejection
      and longer shelf life, make the gamma-irradiated tissue a viable and clinically
      desired option in various ophthalmic procedures.

PMID- 26203755
TI  - Comparative Evaluation of the Corneal and Anterior Chamber Parameters Derived
      From Scheimpflug Imaging in Arab and South Asian Normal Eyes.
AB  - PURPOSE: To evaluate the differences in the normal corneal and anterior segment
      Scheimpflug parameters in Arab and South Asian eyes. METHODS: This hospital-based
      study was performed at a cornea and refractive surgery service in Abu Dhabi. A
      total of 600 consecutive normal candidates of South Asian (group 1, n = 300) and
      Arab (group 2, n = 300) origins underwent Scheimpflug imaging (Sirius;
      Costruzione Strumenti Oftalmici, Italy). One eye was randomly selected for
      evaluation. RESULTS: The age and sex distributions in both groups were
      comparable. The pachymetric variables were statistically higher in group 2 (group
      2 vs. group 1, 544.3 +/- 32.2 MUm vs. 535.1 +/- 31.4 MUm for central corneal
      thickness, 541.0 +/- 32.6 MUm vs. 531.9 +/- 31.5 MUm for minimum corneal
      thickness, 571.7 +/- 43.2 MUm vs. 558.1 +/- 42.3 MUm for apical thickness, and
      58.1 +/- 4.2 vs. 57.3 +/- 4.3 mm3 for the corneal volume; P < 0.05). The anterior
      chamber volume (group 2 vs. group 1: 166.4 +/- 16.4 vs. 161.6 +/- 20.5 mm3) and
      angle (group 2 vs. group 1: 44.6 +/- 6.2 vs. 43.5 +/- 5.8 degrees) were also
      higher for group 2 (P < 0.05). Central corneal curvature and apical corneal
      curvature (apex K) were higher in group 1 (P < 0.05) with comparable astigmatism.
      The flat keratometry (K), steep K, and apex K were 43.6 +/- 2.2 diopters (D),
      44.9 +/- 1.8 D, and 45.7 +/- 1.8 D for group 1, and 43.1 +/- 2.2 D, 44.5 +/- 2 D,
      and 45.2 +/- 1.9 D for group 2. The effect size (Cohen d) for significant
      parameters ranged from 0.2 to 0.3. CONCLUSIONS: Normal eyes of Arab ethnicity
      tend to have statistically thicker and flatter corneas and less-crowded anterior
      segments than those of the South Asian counterparts. These epidemiological
      differences have a mild to moderate biological effect size (Cohen d), but they
      should be considered when evaluating these eyes for anterior segment or corneal
      procedures.

PMID- 26203756
TI  - Superior Perilimbal Epitheliopathy in Recurrent Corneal Erosion Syndrome.
AB  - PURPOSE: To highlight the finding of occult areas of poor epithelial adhesion in
      the superior perilimbal cornea in a minority of patients with recalcitrant
      recurrent corneal erosion syndrome presenting with corneal erosion elsewhere on
      the corneal surface. PATIENT POPULATION: Thirty-one eyes of 31 consecutive
      patients with corneal erosion undergoing mechanical debridement of the epithelium
      before diamond burr keratectomy for recurrent corneal erosion. METHODS: Thirty
      one eyes of 31 consecutive patients with recurrent corneal erosion were examined
      for poor epithelial adhesion determined by mechanical debridement with a dry
      microsponge. RESULTS: During debridement, 8 of 31 eyes (25.8%) displayed a large
      arcuate area of occult dysfunction of adhesion in the superior perilimbal area.
      None of these eyes showed recurrence over a mean of 18 months after diamond burr
      keratectomy (95% confidence interval, 0%-36.9%). CONCLUSIONS: Mechanical
      debridement with a microsponge identified a significant minority of patients with
      poor adhesion in the superior perilimbal cornea away from the area of obvious
      erosion and increased the target area for diamond burr keratectomy. This 2
      pronged approach allowed successful management of this group.

PMID- 26203757
TI  - Phenotypic Investigation of Regenerated Epithelial Cells After Gonococcal Corneal
      Perforation: A Clinical, Histological, and Immunohistochemical Study.
AB  - PURPOSE: To determine the characteristics of regenerated epithelial cells after
      severe gonococcal infection after corneal perforation. METHODS: Pathological
      tissue was obtained from the cornea at the time of surgery. Hematoxylin and eosin
      staining and immunohistochemical analysis were performed for cytoskeletal
      keratins (K12, K13, and K15), basement membrane and junctional markers (laminin
      5, ZO-1 and Desmoplakin), and proliferative and mesenchymal markers (Ki67, alpha
      SMA, and vimentin). RESULTS: A 42-year-old patient with severe gonococcal
      keratoconjunctivitis rapidly progressed to corneal perforation during
      administration of intensive topical and systemic antibiotics. After conservative
      treatment, the perforation healed and 5- * 3-mm corneal ectasia occurred with
      localized iris attachment. Complete closure of the cornea was confirmed by a
      negative Seidel test. After lamellar keratoplasty to improve corneal integrity
      and to prevent secondary glaucoma, the pathological tissue revealed a poorly
      organized epithelial layer at the regenerated ectatic area. The regenerated
      epithelial cells clearly expressed K12, ZO-1, and Desmoplakin with underlying
      laminin 5 (+) basement membrane. K15 and Ki67 expressions were observed
      predominantly at the limbal area but not in the regenerated area. alpha-SMA and
      vimentin were sporadically expressed in the underlying connective tissue.
      CONCLUSIONS: We speculate that the process of epithelial wound healing at the
      site of corneal perforation was responsible for migration of the surrounding
      epithelial cells. Although the regenerated cells expressed several cytokeratins
      and junctional markers, they remained disorganized and fragile.

PMID- 26203758
TI  - Fine-Needle Diathermy Guided by Angiography.

PMID- 26203759
TI  - Management of Limbal Stem Cell Deficiency: A Historical Perspective, Past,
      Present, and Future.
AB  - PURPOSE: To review the management of limbal stem cell deficiency (LSCD) from a
      historical perspective, report the current treatment guidelines, and propose
      potential future treatments. METHODS: A literature review was conducted to
      identify key publications regarding the management of LSCD since treatments were
      first reported. The advances in surgical treatments, as well as postoperative
      management, are described from a historical perspective. In addition, current
      treatment guidelines, as well as future management strategies, are discussed.
      RESULTS: The management of LSCD has changed dramatically during the last several
      decades. Before the understanding of the anatomy and physiology of the limbus,
      all patients with severe LSCD had a dismal prognosis. It was not until the
      understanding of the location and function of the limbal stem cells that
      successful management protocols could be formulated. This research gave rise to
      medical and surgical treatment that protected or replaced diseased or absent
      limbal stem cells. Understanding the role of the conjunctiva in severe ocular
      surface disease was also critical in the management of LSCD. Continued
      improvement in tissue harvesting and surgical techniques have led to improved
      outcomes in LSCD patients. CONCLUSION: Significant progress has been made during
      the last several decades to manage patients with LSCD. A substantial percent of
      patients can achieve improved visual acuity with current techniques. Continued
      research with new cell culture and tissue engineering techniques may be the next
      breakthrough to improve the outcomes for these most challenging patients.

PMID- 26203760
TI  - Robotically Assisted Pterygium Surgery: First Human Case.
AB  - PURPOSE: Little research has been done on robotic ocular microsurgery. This study
      aims to demonstrate the feasibility of pterygium surgery using a robotic surgical
      system. METHODS: Robot-assisted pterygium surgery was performed on a 73-year-old
      patient with nasal and temporal pterygia using the DaVinci Si HD robotic Surgical
      System (Intuitive Surgical Inc). The Kenyon technique (excision coupled with a
      conjunctival autograft) was performed. RESULTS: The DaVinci system provided
      appropriate dexterity to perform the different steps of surgery. The operative
      time was 60 minutes 30 seconds. There were no intraoperative complications and no
      need for conversion to conventional surgery. Postoperative follow-up was
      unremarkable. CONCLUSIONS: Robot-assisted pterygium removal is technically
      feasible using the DaVinci Si HD robotic Surgical System. We report the first
      human case of robot-assisted pterygium surgery.Clinical Trial Registration-URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT02116062.

PMID- 26203761
TI  - Patient-reported outcomes during and after definitive chemoradiotherapy for
      oesophageal cancer.
AB  - BACKGROUND: Limited data describe patient-reported outcomes (PROs) of localised
      oesophageal cancer treated with definitive chemoradiotherapy(CRT). The phase 2/3
      SCOPE-1 trial assessed the effectiveness of CRT+/-cetuximab. The trial for the
      first time provided an opportunity to describe PROs from a multi-centre group of
      patients treated with CRT that are presented here. METHODS: Patients undergoing
      CRT+/-cetuximab within the SCOPE-1 trial (258 patients from 36 UK centres)
      completed generic-, disease- and treatment-specific health-related quality of
      life (HRQL) questionnaires (EORTC QLQ-C30, QLQ-OES18, Dermatology Life-Quality
      Index (DLQI)) at baseline and at 7, 13, 24, 52 and 104 weeks. Mean EORTC
      functional scale scores (>15 point change significant), DLQI scores (>4 point
      change significant) and proportions of patients (>15% significant) with 'minimal'
      or 'severe' symptoms are presented. RESULTS: Questionnaire response rates were
      good. At baseline, EORTC functional scores were high (>75%) and few symptoms were
      reported except for severe problems with fatigue, insomnia and eating-related
      symptoms (e.g., appetite loss, dysphagia, dry mouth) in both groups(>15%).
      Functional aspects of health deteriorated and symptoms increased with treatment
      and by week 13 global quality of life, physical, role and social function
      significantly deteriorated and more problems with fatigue, dyspnoea, appetite
      loss and trouble with taste were reported. Recovery occurred by 6 months (except
      severe fatigue and insomnia in >15% of patients) and maintained at follow-up with
      no differences between groups. CONCLUSIONS: CRT for localised oesophageal cancer
      has a significant detrimental impact on many aspects of HRQL; however, recovery
      is achieved by 6 months and maintained with the exception of persisting problems
      with severe fatigue and insomnia. The data suggest that the HRQL recovery after
      definitive CRT is quicker, and there is little lasting deficit compared with
      treatment including surgery. These data need to be compared with HRQL data from
      studies evaluating treatments including surgery for oesophageal cancer.

PMID- 26203763
TI  - Prevalence of 16S rRNA Methylase Gene rmtB Among Escherichia coli Isolated from
      Bovine Mastitis in Ningxia, China.
AB  - The aim of this study is to understand the prevalence and molecular
      characterization of 16S rRNA methylase gene, rmtB, among Escherichia coli strains
      isolated from bovine mastitis in China. A total of 245 E. coli isolates were
      collected from bovine mastitis in China between 2013 and 2014 and were screened
      for 16S rRNA methylase genes (armA, rmtA, rmtB, rmtC, rmtD, rmtE, and npmA) by
      polymerase chain reaction. About 5.3% (13/245) of the isolates carried the rmtB
      gene; the isolates were highly resistant to amikacin. Thirteen rmtB-positive
      strains were analyzed for the presence of extended-spectrum beta-lactamase genes
      (bla(TEM), bla(CTX-M), bla(OXA), and bla(SHV)). All the isolates harbored both
      bla(TEM-1) and bla(CTX-M-15) genes and two of the isolates were also positive for
      bla(OXA-1). Pulsed-field gel electrophoresis (PFGE) analysis indicated that the
      nine rmtB-positive strains belonging to ST10 from one farm showed the similar
      PFGE pattern, indicating a clonal expansion in this farm. S1-PFGE and Southern
      blotting showed that 12 isolates harbored the rmtB gene in plasmids of two
      different sizes (~45 kb [n=10] and ~48 kb [n=2]), while only 1 strain harbored
      the rmtB gene in the chromosome. These plasmids were transferable by conjugation
      studies, and two isolates from two respective farms carried the same size of
      plasmid, suggesting that the horizontal transmission of plasmids also contributed
      to the spread of rmtB gene. This is the first report of prevalence of the 16S
      rRNA methylase gene rmtB among E. coli isolated from bovine mastitis in China,
      and rmtB-carrying E. coli may pose a threat to the treatment of bovine mastitis.

PMID- 26203762
TI  - Construction of therapeutically relevant human prostate epithelial fate map by
      utilising miRNA and mRNA microarray expression data.
AB  - BACKGROUND: Objective identification of key miRNAs from transcriptomic data is
      difficult owing to the inherent inconsistencies within miRNA target-prediction
      algorithms and the promiscuous nature of miRNA-mRNA target relationship. METHODS:
      An integrated database of miRNAs and their 'relevant' mRNA targets was generated
      from validated miRNA and mRNA microarray data sets generated from patient-derived
      prostate epithelial normal and cancer stem-like cells (SCs) and committed basal
      (CB) cells. The effect of miR-542-5p inhibition was studied to provide proof-of
      principle for database utility. RESULTS: Integration of miRNA-mRNA databases
      showed that signalling pathways and processes can be regulated by a single or
      relatively few miRNAs, for example, DNA repair/Notch pathway by miR-542-5p,
      P=0.008. Inhibition of miR-542-5p in CB cells (thereby achieving miR-542-5p
      expression levels similar to SCs) promoted efficient DNA repair and activated
      expression of Notch reporters, HES1 and Survivin, without inducing
      dedifferentiation into SCs. CONCLUSIONS: Our novel framework impartially
      identifies therapeutically relevant miRNA candidates from transcriptomic data
      sets.

PMID- 26203764
TI  - Protein Z efficiently depletes thrombin generation in disseminated intravascular
      coagulation with poor prognosis.
AB  - Disseminated intravascular coagulation (DIC) is characterized by consumption of
      coagulation factors and anticoagulants. Thrombin generation assay (TGA) gives
      useful information about global hemostatic status. We developed a new TGA system
      that anticoagulant addition can deplete thrombin generation in plasma, which may
      reflect defective anticoagulant system in DIC. TGAs were measured on the
      calibrated automated thrombogram with and without thrombomodulin or protein Z in
      152 patients who were suspected of having DIC, yielding four parameters including
      lag time, endogenous thrombin potential, peak thrombin and time-to-peak in each
      experiment. Nonsurvivors showed significantly prolonged lag time and time-to-peak
      in TGA-protein Z system, which was performed with added protein Z. In
      multivariate Cox regression analysis, lag time and time-to-peak in TGA system
      were significant independent prognostic factors. In TGA-protein Z system, lag
      time and time-to-peak were revealed as independent prognostic factors of DIC.
      Protein Z addition could potentiate its anticoagulant effect in DIC with poor
      prognosis, suggesting the presence of defective protein Z system. The prolonged
      lag time and time-to-peak in both TGA and TGA-protein Z systems are expected to
      be used as independent prognostic factors of DIC. 

PMID- 26203765
TI  - Extreme warfarin hypersensitivity after oophorectomy.
AB  - We report the case of a woman who developed unexplained warfarin hypersensitivity
      after undergoing surgery to remove her ovaries. Presurgery, the patient's
      international normalised ratios (INR) control was stable and uneventful but 11
      days after her operation she presented with extremely high (frequently >=10) INR.
      Warfarin was discontinued on day 24 postoperation but 11 days later the plasma
      warfarin concentration was high at 4.8 mg/l (therapeutic range 0.7-2.3 mg/l).
      After cessation of warfarin, she required frequent doses of oral and intravenous
      vitamin K1 (totalling 48 mg) as well as two doses of prothrombin complex
      concentrate to normalise the INR. The patient was switched from warfarin to
      heparin, then to dabigatran with no further thrombosis or bleeding. While on
      heparin, the kinetics of warfarin elimination and vitamin K status were found to
      be normal and the reason for the onset of the extreme sensitivity to warfarin
      remains unknown. 

PMID- 26203766
TI  - The effect of factors other than age upon skeletal age indicators in the adult.
AB  - CONTEXT: Estimation of adult age from skeletal remains is problematic due to the
      weak and variable relationship between age indicators and age. OBJECTIVES: To
      assess the proportion of variation in age indicators that is associated with
      factors other than age and to attempt to identify what those factors might be.
      METHODS: The paper focuses on frequently used adult bony age markers. A
      literature search (principally using Web of Science) is conducted to assess the
      proportion of variation in age indicators associated with factors other than age.
      The biology of these age markers is discussed, as are factors other than age that
      might affect their expression. RESULTS: Typically, ~60% of variation in bony age
      indicators is associated with factors other than age. Factors including inherent
      metabolic propensity to form bone in soft tissue, vitamin D status, hormonal and
      reproductive factors, energy balance, biomechanical variables and genetic factors
      may be responsible for this variation, but empirical studies are few. CONCLUSION:
      Most variation in adult skeletal age markers is due to factors other than age;
      dry bone study of historic documented skeletal collections and high resolution CT
      scanning in modern cadavers or living individuals is needed to identify these
      factors.

PMID- 26203767
TI  - Gene polymorphisms related to insulin resistance and gene-environment interaction
      in colorectal cancer risk.
AB  - BACKGROUND AND AIM: Insulin resistance (IR) is an established risk factor for
      colorectal cancer (CRC) and both IR and CRC physiologically overlap. As such,
      this study explored the relationship of IR-related gene polymorphisms and CRC
      risk. SUBJECTS AND METHODS: A total of 400 case-control pairs were profiled in
      terms of their lifestyle, dietary habits and blood sample. Classification and
      regression tree (CART) and generalized multi-factor dimensionality reduction
      (GMDR) were employed to test the gene-environment interactions in CRC risk.
      RESULTS: ADIPOQ rs2241766 TG + GG, ADIPOQ rs1501299 GT + TT and CAPN-10 rs3792267
      GA + AA were significantly related to CRC risk. In CART, individuals with high
      red meat consumption, CAPN-10 rs3792267 GG, ADIPOQ rs1501299 GG and ADIPOQ
      rs2241766 TG + GG had an OR of 1.821 (95% CI = 1.124-2.951). The overall best
      GMDR model including the four factors had the maximal TBA (0.5943) and CVC
      (10/10) (p = 0.0010). Subjects with high red meat consumption and the three risk
      genotypes had a CRC risk 10.195-times (95% CI = 2.164-48.030) greater than those
      with low red meat and null risk genotypes. CONCLUSIONS: ADIPOQ rs2241766, ADIPOQ
      rs1501299 and CAPN-10 rs3792267 are significantly associated with CRC risk and
      the combination of the three polymorphisms and red meat affect CRC risk.

PMID- 26203769
TI  - Iron-Catalyzed Reduction of CO2 into Methylene: Formation of C-N, C-O, and C-C
      Bonds.
AB  - We report herein the use of the (dihydrido)iron catalyst, Fe(H)2(dmpe)2, for the
      selective reduction of CO2 into either bis(boryl)acetal or methoxyborane
      depending on the hydroborane used as a reductant. In a one-pot two-step
      procedure, the in situ generated bis(boryl)acetal was shown to be a reactive and
      versatile source of methylene to create new C-N but also C-O and C-C bonds. 

PMID- 26203770
TI  - Location of the High-Affinity Mn(2+) Site in Photosystem II Detected by PELDOR.
AB  - The location of the high-affinity Mn(2+) site in apo-photosystem (PS) II was
      investigated by pulsed EPR. The electron-electron magnetic dipole interaction of
      1.7 MHz between the YD(*) radical and Mn(2+) ion was observed using the pulsed
      electron-electron double resonance (PELDOR) technique, and the Mn(2+) ion was
      bound to one apo-PS II in the absence and presence of Ca(2+). PELDOR signals were
      calculated using the previously determined spin distribution on the YD(*) radical
      and its known position in the crystal structure, assuming that the specific
      Mn(2+) site was located in the oxygen evolving complex. The results show that the
      high-affinity Mn(2+) site is located at the position denoted by Mn4(A) in the
      native crystal structure. The Mn(2+) is coordinated with axial ligands Asp170 and
      Glu333 in the D1 polypeptide. 

PMID- 26203768
TI  - High Affinity Dopamine D3 Receptor (D3R)-Selective Antagonists Attenuate Heroin
      Self-Administration in Wild-Type but not D3R Knockout Mice.
AB  - The dopamine D3 receptor (D3R) is a promising target for the development of
      pharmacotherapeutics to treat substance use disorders. Several D3R-selective
      antagonists are effective in animal models of drug abuse, especially in models of
      relapse. Nevertheless, poor bioavailability, metabolic instability, and/or
      predicted toxicity have impeded success in translating these drug candidates to
      clinical use. Herein, we report a series of D3R-selective 4-phenylpiperazines
      with improved metabolic stability. A subset of these compounds was evaluated for
      D3R functional efficacy and off-target binding at selected 5-HT receptor
      subtypes, where significant overlap in SAR with D3R has been observed. Several
      high affinity D3R antagonists, including compounds 16 (Ki = 0.12 nM) and 32 (Ki =
      0.35 nM), showed improved metabolic stability compared to the parent compound,
      PG648 (6). Notably, 16 and the classic D3R antagonist SB277011A (2) were
      effective in reducing self-administration of heroin in wild-type but not D3R
      knockout mice. 

PMID- 26203771
TI  - The downregulation of DeltaNp63 in p53-deficient mouse epidermal tumors favors
      metastatic behavior.
AB  - The TP63 gene codes for two major isoform types, TAp63 and DeltaNp63, with
      probable opposite roles in tumorigenesis. The DeltaNp63alpha protein is
      frequently amplified and overexpressed in different epithelial tumors.
      Accordingly, it has been considered a potential oncogene. Nonetheless, a possible
      metastatic suppressor activity has also been suggested based on the experimental
      observation that its expression is reduced or even absent in advanced invasive
      tumors. Such metastatic suppressor activities are often related to tumors bearing
      point mutated TP53 gene. However, its potential roles in TP53-deficient tumors
      are poorly characterized. Here we show that in spontaneous tumors, induced by the
      epidermal-specific Trp53 ablation, the reduction of DeltaNp63 expression is an
      early event, whereas it is re-expressed in the lung metastatic lesions. Using
      knock down and ectopic expression approaches, we show that DeltaNp63 expression
      opposes the epithelial-mesenchymal transition and reduces the metastatic
      potential of the cells. This process occurs through the modulation of DeltaNp63
      dependent downstream targets (including transcription factors and microRNAs)
      likely to play metastatic roles. Further, DeltaNp63 also favors the expression of
      factors involved in iPS reprogramming, thus suggesting that it can also modulate
      specific stem cell traits in mouse epidermal tumor cells. Overall, our data
      assign antimetastatic roles to DeltaNp63 in the context of p53 deficiency and
      epidermis. 

PMID- 26203773
TI  - Multimodal imaging guided preclinical trials of vascular targeting in prostate
      cancer.
AB  - The high mortality rate associated with castration-resistant prostate cancer
      (CRPC) underscores the need for improving therapeutic options for this patient
      population. The purpose of this study was to examine the potential of vascular
      targeting in prostate cancer. Experimental studies were carried out in
      subcutaneous and orthotopic Myc-CaP prostate tumors implanted into male FVB mice
      to examine the efficacy of a novel microtubule targeted vascular disrupting agent
      (VDA), EPC2407 (CrolibulinTM). A non-invasive multimodality imaging approach
      based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and
      ultrasound (US) was utilized to guide preclinical trial design and monitor tumor
      response to therapy. Imaging results were correlated with histopathologic
      assessment, tumor growth and survival analysis. Contrast-enhanced MRI revealed
      potent antivascular activity of EPC2407 against subcutaneous and orthotopic Myc
      CaP tumors. Longitudinal BLI of Myc-CaP tumors expressing luciferase under the
      androgen response element (Myc-CaP/ARE-luc) revealed changes in AR signaling and
      reduction in intratumoral delivery of luciferin substrate following castration
      suggestive of reduced blood flow. This reduction in blood flow was validated by
      US and MRI. Combination treatment resulted in sustained vascular suppression,
      inhibition of tumor regrowth and conferred a survival benefit in both models.
      These results demonstrate the therapeutic potential of vascular targeting in
      combination with androgen deprivation against prostate cancer. 

PMID- 26203774
TI  - The antidiabetic compound 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione,
      isolated from Averrhoa carambola L., demonstrates significant antitumor potential
      against human breast cancer cells.
AB  - 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione
      found in the roots of Averrhoa carambola L., commonly known as starfruit.
      Researchers have shown that DMDD has significant therapeutic potential for the
      treatment of diabetes; however, the effects of DMDD on human cancers have never
      been reported. We investigated the cytotoxic effects of DMDD against human
      breast, lung and bone cancer cells in vitro and further examined the molecular
      mechanisms of DMDD-induced apoptosis in human breast cancer cells. DMDD
      suppressed the growth of breast carcinoma cells, but not normal mammary
      epithelial cells, via induction of G1 phase cell cycle arrest, oxidative stress
      and apoptosis. DMDD increased the level of intracellular reactive oxygen species
      (ROS) and DMDD-induced ROS generation was found to be associated with the
      mitochondrial activity. The cytotoxicity that was induced by DMDD was attenuated
      by co-treatment with the antioxidant N-acetyl-L-cysteine (NAC). DMDD-induced cell
      apoptosis involved the activation of both the intrinsic mitochondrial pathway and
      the extrinsic receptor pathway. In addition, DMDD inhibited the canonical NF
      kappaB signaling pathway at all steps, including TNF-alpha production,
      phosphorylation of NF-kappaB p65 and IkappaBalpha, as well as TNF-alpha activated
      NF-kappaB p65 nuclear translocation.Collectively, our studies indicate that DMDD
      has significant potential as a safe and efficient therapeutic agent for the
      treatment of breast cancer. 

PMID- 26203776
TI  - Synthesis of 1,3-Amino Alcohols, 1,3-Diols, Amines, and Carboxylic Acids from
      Terminal Alkynes.
AB  - The half-sandwich ruthenium complexes 1-3 activate terminal alkynes toward anti
      Markovnikov hydration and reductive hydration under mild conditions. These
      reactions are believed to proceed via addition of water to metal vinylidene
      intermediates (4). The functionalization of propargylic alcohols by metal
      vinylidene pathways is challenging owing to decomposition of the starting
      material and catalytic intermediates. Here we show that catalyst 2 can be
      employed to convert propargylic alcohols to 1,3-diols in high yield and with
      retention of stereochemistry at the propargylic position. The method is also
      amenable to propargylic amine derivatives, thereby establishing a route to
      enantioenriched 1,3-amino alcohol products. We also report the development of
      formal anti-Markovnikov reductive amination and oxidative hydration reactions to
      access linear amines and carboxylic acids, respectively, from terminal alkynes.
      This chemistry expands the scope of products that can be prepared from terminal
      alkynes by practical and high-yielding metal-catalyzed methods. 

PMID- 26203775
TI  - "CRISPR" validation of recessive brain cancer genes in vivo.

PMID- 26203772
TI  - Radio-resistant mesenchymal stem cells: mechanisms of resistance and potential
      implications for the clinic.
AB  - Mesenchymal stem cells (MSCs) comprise a heterogeneous population of multipotent
      stromal cells and can be isolated from various tissues and organs. Due to their
      regenerative potential, they have been subject to intense research efforts, and
      they may provide an efficient means for treating radiation-induced tissue damage.
      MSCs are relatively resistant to ionizing radiation and retain their stem cell
      characteristics even after high radiation doses. The underlying mechanisms for
      the observed MSC radioresistance have been extensively studied and may involve
      efficient DNA damage recognition, double strand break repair and evasion of
      apoptosis. Here, we present a concise review of the published scientific data on
      the radiobiological features of MSCs. The involvement of different DNA damage
      recognition and repair pathways in the creation of a radioresistant MSC phenotype
      is outlined, and the roles of apoptosis, senescence and autophagy regarding the
      reported radioresistance are summarized. Finally, potential influences of the
      radioresistant MSCs for the clinic are discussed with respect to the repair and
      radioprotection of irradiated tissues. 

PMID- 26203777
TI  - Nanowire Oriented On-Surface Growth of Chiral Cystine Crystalline Nanosheets.
AB  - Exploration of an effective route to achieve the controlled growth of two
      dimensional (2D) molecular crystal is of scientific significance yet greatly
      underdeveloped due to the complexity of weak intermolecular interactions, thus
      leading to difficulty of inducing anisotropic 2D growth. We report here a facile
      nanowire oriented on-surface growth strategy for the fabrication of cystine
      crystalline nanosheets with finely controlled thickness (1.1, 1.9, 2.9, and 4.8
      nm which correspond to one layer, two layers, three layers, and five layers of
      crystal cystine, respectively) and large areas (>100 MUm(2)). The cystine
      crystalline nanosheets display chirality delivered by chiral cysteine monomers,
      either l-cysteine or d-cysteine. The chiral nanosheets with structural precision
      and chemical diversity could serve as a novel 2D platform for constructing
      advanced hybrid materials. 

PMID- 26203779
TI  - Half-Metallic Ferromagnetism and Surface Functionalization-Induced Metal
      Insulator Transition in Graphene-like Two-Dimensional Cr2C Crystals.
AB  - Graphene-like two-dimensional materials have garnered tremendous interest as
      emerging device materials for nanoelectronics due to their remarkable properties.
      However, their applications in spintronics have been limited by the lack of
      intrinsic magnetism. Here, using hybrid density functional theory, we predict
      ferromagnetic behavior in a graphene-like two-dimensional Cr2C crystal that
      belongs to the MXenes family. The ferromagnetism, arising from the itinerant Cr d
      electrons, introduces intrinsic half-metallicity in Cr2C MXene, with the half
      metallic gap as large as 2.85 eV. We also demonstrate a ferromagnetic
      antiferromagnetic transition accompanied by a metal to insulator transition in
      Cr2C, caused by surface functionalization with F, OH, H, or Cl groups. Moreover,
      the energy gap of the antiferromagnetic insulating state is controllable by
      changing the type of functional groups. We further point out that the
      localization of Cr d electrons induced by the surface functionalization is
      responsible for the ferromagnetic-antiferromagnetic and metal to insulator
      transitions. Our results highlight a new promising material with tunable magnetic
      and electronic properties toward nanoscale spintronics and electronics
      applications. 

PMID- 26203780
TI  - Preceptor and Self-Evaluation Competencies Among New RN Graduates.

PMID- 26203778
TI  - Activatable and Cell-Penetrable Multiplex FRET Nanosensor for Profiling MT1-MMP
      Activity in Single Cancer Cells.
AB  - We developed a quantum-dot-based fluorescence resonance energy transfer (QD-FRET)
      nanosensor to visualize the activity of matrix metalloproteinase (MT1-MMP) at
      cell membrane. A bended peptide with multiple motifs was engineered to position
      the FRET pair at a close proximity to allow energy transfer, which can be cleaved
      by active MT1-MMP to result in FRET changes and the exposure of cell penetrating
      sequence. Via FRET and penetrated QD signals, the nanosensor can profile cancer
      cells. 

PMID- 26203782
TI  - 3D Graphene Functionalized by Covalent Organic Framework Thin Film as Capacitive
      Electrode in Alkaline Media.
AB  - To harness the electroactivity of anthraquinone as an electrode material, a great
      recent effort have been invested to composite anthraquinone with carbon materials
      to improve the conductivity. Here we report on a noncovalent way to modify three
      dimensional graphene with anthraquinone moieties through on-surface synthesis of
      two-dimensional covalent organic frameworks. We incorporate 2,6-diamino
      anthraquinone moieties into COF through Schiff-base reaction with benzene-1,3,5
      tricarbaldehyde. The synthesized COF -graphene composite exhibits large specific
      capacitance of 31.7 mF/cm(2). Long-term galvanostatic charge/discharge cycling
      experiments revealed a decrease of capacitance, which was attributed to the loss
      of COF materials and electrostatic repulsion accumulated during charge-discharge
      circles which result in the poor electrical conductivity between 2D COF layers. 

PMID- 26203781
TI  - When Indolizine Meets Quinoline: Diversity-Oriented Synthesis of New
      Polyheterocycles and Their Optical Properties.
AB  - Fluorescence-based technologies play a pivotal role in various biomedical
      applications. Here we report an efficient route to a new class of fluorophores,
      indolizino[3,2-c]quinolines, via the oxidative Pictet-Spengler cyclization
      strategy. The condensation of several 2-methylpyridines with 2-bromo-2'
      nitroacetophenone allowed for the rapid assembly of indolizines with a 2
      nitrophenyl group at the C2 position. The subsequent reduction of the nitro group
      under mild conditions followed by oxidative Pictet-Spengler cyclization with
      various aryl aldehydes in the presence of a catalytic amount of FeCl3 furnished
      the indolizino[3,2-c]quinolines in good overall yields. We also examined the
      photophysical properties of this new series of polyheterocyclic compounds.
      Several indolizino[3,2-c]quinolines were found to have unique and desirable
      optical properties, suggesting that these compounds may be suitable for use as
      prospective fluorescent probes in aqueous systems. 

PMID- 26203783
TI  - Strength order and nature of the pi-hole bond of cyanuric chloride and 1,3,5
      triazine with halide.
AB  - The (13)C NMR chemical shift moving upfield indicates the main model of pi-holeX(
      ) bond between cyanuric chloride/1,3,5-triazine (3ClN/3N), which possess both the
      pi-hole and sigma-hole, and X(-). (13)C NMR and UV absorption titration in
      acetonitrile confirmed that the bonding abilities of 3ClN/3N with X(-) follow the
      order I(-) > Br(-) > Cl(-), which is apparently the order of the charge transfer
      ability of halide to 3ClN/3N. Chemical calculations showed that the bonding
      abilities in solution were essentially consistent with those obtained by
      titration experiments. However, the results in the gas phase were the reverse,
      i.e., pi-holeCl(-) > pi-holeBr(-) > pi-holeI(-) in bonding energy, which obeys
      the order of electrostatic interaction. In fact, the pi-hole bond and sigma-hole
      bond compete with solvation and possible anion-hydrogen bond between a solvent
      molecule and a halide in solution. An explanation is that the apparent charge
      transfer order of pi-/sigma-holeI(-) > pi-/sigma-holeBr(-) > pi-/sigma-holeCl(-)
      occurs for weak pi-hole bonds and sigma-hole bonds, whereas the order of
      electrostatic attraction of pi-/sigma-holeCl(-) > pi-/sigma-holeBr(-) > pi-/sigma
      holeI(-) is valid for strong bonds. It can be concluded by combining energy
      decomposition analysis and natural bond orbital analysis that the pi-holeX(-)
      bond and sigma-holeX(-) bond are electrostatically attractive in nature
      regardless of whether the order is I(-) > Br(-) > Cl(-) or the reverse. 

PMID- 26203784
TI  - Supramolecular polymer adhesives: advanced materials inspired by nature.
AB  - Due to their dynamic, stimuli-responsive nature, non-covalent interactions
      represent versatile design elements that can be found in nature in many molecular
      processes or materials, where adaptive behavior or reversible connectivity is
      required. Examples include molecular recognition processes, which trigger
      biological responses or cell-adhesion to surfaces, and a broad range of animal
      secreted adhesives with environment-dependent properties. Such advanced
      functionalities have inspired researchers to employ similar design approaches for
      the development of synthetic polymers with stimuli-responsive properties. The
      utilization of non-covalent interactions for the design of adhesives with
      advanced functionalities such as stimuli responsiveness, bonding and debonding on
      demand capability, surface selectivity or recyclability is a rapidly emerging
      subset of this field, which is summarized in this review. 

PMID- 26203785
TI  - Enhanced electrochemical performance by unfolding a few wings of graphene
      nanoribbons of multiwalled carbon nanotubes as an anode material for Li ion
      battery applications.
AB  - The present work provides an incredible route towards achieving the ideal Li ion
      battery anode material with high specific capacity and rate capability as a
      result of unraveling a few upper layers of multiwalled carbon nanotubes (MWNTs)
      as graphene nanoribbons attached to the core MWNT. These partially exfoliated
      nanotubes when used as an anode material show an 880 mA h g(-1) capacity at a 100
      mA g(-1) current density and high rate capability by delivering a stable 157 mA h
      g(-1) capacity at a current density of 10 A g(-1). The enhanced performance of
      this anode material can be attributed to the synergistic effect of the
      homogeneous distribution of the hybrid carbon nanostructure of 1-D multiwalled
      carbon nanotubes and 2-D graphene nanoribbons. This configuration provides a
      large available surface area, high electrical conductivity and a high number of
      defect sites, leading to improved Li intercalation with a better transfer rate
      compared to only graphene, multiwalled carbon nanotubes or other reported
      combinations of the two. 

PMID- 26203786
TI  - Singlet-Triplet Gaps of Cobalt Nitrosyls: Insights from Tropocoronand Complexes.
AB  - A density functional theory (DFT) study of {CoNO}(8) cobalt nitrosyl complexes
      containing the [n,n]tropocoronand ligand (TC-n,n) has revealed a sharp reduction
      of singlet-triplet gaps as the structures change from near-square-pyramidal (for
      n = 3) to trigonal-bipyramidal with an equatorial NO (for n = 5, 6). An
      experimental reinvestigation of [Co(TC-3,3)(NO)] has confirmed that it is not
      paramagnetic, as originally reported, but diamagnetic, like all other {CoNO}(8)
      complexes. Furthermore, DFT calculations indicate a substantial singlet-triplet
      gap of about half an eV or higher for this complex. At the other end of the
      series, low-energy, thermally accessible triplet states are predicted for [Co(TC
      6,6)(NO)]. Enhanced triplet-state reactivity may well provide a partial
      explanation for the failure to isolate this compound as a stable species. 

PMID- 26203787
TI  - Efficient perovskite solar cells fabricated using an aqueous lead nitrate
      precursor.
AB  - A novel, aqueous precursor system (Pb(NO3)2 + water) is developed to replace
      conventional (PbI2 + DMF) for fabricating methylammonium lead iodide (MAPbI3)
      perovskite solar cells (PSCs). When the morphology and surface coverage of the
      Pb(NO3)2 film was controlled during coating, a power conversion efficiency of
      12.58% under standard conditions (AM1.5, 100 mW cm(-2)) was achieved for the PSC.

PMID- 26203788
TI  - One-pot synthesis of 1,3-enynes with a CF3 group on the terminal sp(2) carbon by
      an oxidative Sonogashira cross-coupling reaction.
AB  - Oxidative Sonogashira cross-coupling reactions of (E)-trimethyl(3,3,3
      trifluoroprop-1-enyl)silane with arylacetylene were achieved using silver
      fluoride and a palladium catalyst, to afford high yields of various 1,3-enynes
      with a CF3 group on the terminal sp(2) carbon. Silver fluoride promoted C-Si bond
      dissociation and oxidation of palladium, enabling catalytic use of palladium. 

PMID- 26203789
TI  - Evolution of the magnetic structure with chemical composition in spinel iron
      oxide nanoparticles.
AB  - Magnetic properties of iron oxide nanoparticles with spinel structure are
      strictly related to a complex interplay between cationic distribution and the
      presence of a non-collinear spin structure (spin canting). With the aim to gain
      better insight into the effect of the magnetic structure on magnetic properties,
      in this paper we investigated a family of small crystalline ferrite nanoparticles
      of the formula CoxNi1-xFe2O4 (0 <=x<= 1) having equal size (~4.5 nm) and
      spherical-like shape. The field dependence of magnetization at low temperatures
      indicated a clear increase of magnetocrystalline anisotropy and saturation
      magnetization (higher than the bulk value for CoFe2O4: ~130 A m(2) kg(-1)) with
      the increase of cobalt content. The magnetic structure of nanoparticles has been
      investigated by Mossbauer spectroscopy under an intense magnetic field (8 T) at a
      low temperature (10 K). The magnetic properties have been explained in terms of
      an evolution of the magnetic structure with the increase of cobalt content. In
      addition a direct correlation between cationic distribution and spin canting has
      been proposed, explaining the presence of a noncollinear spin structure in terms
      of superexchange interaction energy produced by the average cationic distribution
      and vacancies in the spinel structure. 

PMID- 26203790
TI  - Interpretability of Change Scores in Measures of Balance in People With COPD.
AB  - BACKGROUND: Balance deficits and an increased fall risk are well documented in
      individuals with COPD. Despite evidence that balance training programs can
      improve performance on clinical balance tests, their minimal clinically important
      difference (MCID) is unknown. The aim of this study was to determine the MCID of
      the Berg Balance Scale (BBS), Balance Evaluation Systems Test (BESTest), and
      Activities-Specific Balance Confidence (ABC) scale in patients with COPD
      undergoing pulmonary rehabilitation. METHODS: We performed a secondary analysis
      of data from two studies of balance training in COPD (n = 55). The MCID for each
      balance measure was estimated using the following anchor and distribution-based
      approaches: (1) mean change scores on a patient-reported global change in balance
      scale, (2) optimal cut-point from receiver operating characteristic curves
      (ROCs), and (3) the minimal detectable change with 95% confidence (MDC95).
      RESULTS: Data from 55 patients with COPD (mean age, 71.2 +/- 7.1 y; mean FEV1,
      39.2 +/- 15.8% predicted) were used in the analysis. The smallest estimate of
      MCID was from the ROC method. Anchor-based estimates of the MCID ranged from 3.5
      to 7.1 for the BBS, 10.2 to 17.4 for the BESTest, and 14.2 to 18.5 for the ABC
      scale; their MDC95 values were 5.0, 13.1, and 18.9, respectively. CONCLUSIONS:
      Among patients with COPD undergoing pulmonary rehabilitation, a change of 5 to 7
      points for the BBS, 13 to 17 points for the BESTest, and 19 points for the ABC
      scale is required to be both perceptible to patients and beyond measurement
      error.

PMID- 26203791
TI  - Pyramid-Shaped Wurtzite CdSe Nanocrystals with Inverted Polarity.
AB  - We report on pyramid-shaped wurtzite cadmium selenide (CdSe) nanocrystals (NCs),
      synthesized by hot injection in the presence of chloride ions as shape-directing
      agents, exhibiting reversed crystal polarity compared to former reports. Advanced
      transmission electron microscopy (TEM) techniques (image-corrected high
      resolution TEM with exit wave reconstruction and probe-corrected high-angle
      annular dark field-scanning TEM) unequivocally indicate that the triangular base
      of the pyramids is the polar (0001) facet and their apex points toward the [0001]
      direction. Density functional theory calculations, based on a simple model of
      binding of Cl(-) ions to surface Cd atoms, support the experimentally evident
      higher thermodynamic stability of the (0001) facet over the (0001) one conferred
      by Cl(-) ions. The relative stability of the two polar facets of wurtzite CdSe is
      reversed compared to previous experimental and computational studies on Cd
      chalcogenide NCs, in which no Cl-based chemicals were deliberately used in the
      synthesis or no Cl(-) ions were considered in the binding models. Self-assembly
      of these pyramids in a peculiar clover-like geometry, triggered by the addition
      of oleic acid, suggests that the basal (polar) facet has a density and perhaps
      type of ligands significantly different from the other three facets, since the
      pyramids interact with each other exclusively via their lateral facets. A
      superstructure, however with no long-range order, is observed for clovers with
      their (0001) facets roughly facing each other. The CdSe pyramids were also
      exploited as seeds for CdS pods growth, and the peculiar shape of the derived
      branched nanostructures clearly arises from the inverted polarity of the seeds. 

PMID- 26203793
TI  - Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma.
AB  - IMPORTANCE: Vascular factors may have important roles in the pathophysiology of
      glaucoma. A practical method for the clinical evaluation of ocular perfusion is
      needed to improve glaucoma management. OBJECTIVE: To detect peripapillary retinal
      perfusion in glaucomatous eyes compared with normal eyes using optical coherence
      tomography (OCT) angiography. DESIGN, SETTING, AND PARTICIPANTS: Prospective
      observational study performed from July 24, 2013, to April 17, 2014. Participants
      were recruited and tested at Casey Eye Institute, Oregon Health & Science
      University. In total, 12 glaucomatous eyes and 12 age-matched normal eyes were
      analyzed. The optic disc region was imaged twice using a 3 * 3-mm scan by a 70
      kHz, 840-nm-wavelength spectral OCT system. The split-spectrum amplitude
      decorrelation angiography algorithm was used. Peripapillary flow index was
      calculated as the mean decorrelation value in the peripapillary region, defined
      as a 700-um-wide elliptical annulus around the disc. Peripapillary vessel density
      was the percentage area occupied by vessels. The data statistical analysis was
      performed from October 30, 2013, to May 30, 2014. MAIN OUTCOMES AND MEASURES:
      Variability was assessed by the coefficient of variation. The Mann-Whitney test
      was used to compare the 2 groups of eyes. Correlations between vascular and
      visual field variables were assessed by linear regression analysis. RESULTS: In
      12 normal eyes, a dense microvascular network around the disc was visible on OCT
      angiography. In 12 glaucomatous eyes, this network was visibly attenuated
      globally and focally. In normal eyes, between-visit reproducibilities of
      peripapillary flow index and peripapillary vessel density were 4.3% and 2.7% of
      the coefficient of variation, respectively, while the population variabilities of
      peripapillary flow index and peripapillary vessel density were 8.2% and 3.0% of
      the coefficient of variation, respectively. Peripapillary flow index and
      peripapillary vessel density in glaucomatous eyes were lower than those in normal
      eyes (P < .001 for both). Peripapillary flow index (Pearson r = -0.808) and
      peripapillary vessel density (Pearson r = -0.835) were highly correlated with
      visual field pattern standard deviation in glaucomatous eyes (P = .001 for both).
      The areas under the receiver operating characteristic curve for normal vs
      glaucomatous eyes were 0.892 for peripapillary flow index and 0.938 for
      peripapillary vessel density. CONCLUSIONS AND RELEVANCE: Using OCT angiography,
      reduced peripapillary retinal perfusion in glaucomatous eyes can be visualized as
      focal defects and quantified as peripapillary flow index and peripapillary vessel
      density, with high repeatability and reproducibility. Quantitative OCT
      angiography may have value in future studies to determine its potential
      usefulness in glaucoma evaluation.

PMID- 26203795
TI  - ?

PMID- 26203794
TI  - Physician Estimations of the Risk of Gastrointestinal Stromal Tumor Recurrence-
      Not Accurate Enough?: More Education May Be Needed.

PMID- 26203797
TI  - ?

PMID- 26203796
TI  - ?

PMID- 26203798
TI  - ?

PMID- 26203799
TI  - ?

PMID- 26203800
TI  - Targeted Type 2 Alveolar Cell Depletion. A Dynamic Functional Model for Lung
      Injury Repair.
AB  - Type 2 alveolar epithelial cells (AEC2) are regarded as the progenitor population
      of the alveolus responsible for injury repair and homeostatic maintenance.
      Depletion of this population is hypothesized to underlie various lung
      pathologies. Current models of lung injury rely on either uncontrolled,
      nonspecific destruction of alveolar epithelia or on targeted, nontitratable
      levels of fixed AEC2 ablation. We hypothesized that discrete levels of AEC2
      ablation would trigger stereotypical and informative patterns of repair. To this
      end, we created a transgenic mouse model in which the surfactant protein-C
      promoter drives expression of a mutant SR39TK herpes simplex virus-1 thymidine
      kinase specifically in AEC2. Because of the sensitivity of SR39TK, low doses of
      ganciclovir can be administered to these animals to induce dose-dependent AEC2
      depletion ranging from mild (50%) to lethal (82%) levels. We demonstrate that
      specific levels of AEC2 depletion cause altered expression patterns of apoptosis
      and repair proteins in surviving AEC2 as well as distinct changes in distal lung
      morphology, pulmonary function, collagen deposition, and expression of remodeling
      proteins in whole lung that persist for up to 60 days. We believe SPCTK mice
      demonstrate the utility of cell-specific expression of the SR39TK transgene for
      exerting fine control of target cell depletion. Our data demonstrate, for the
      first time, that specific levels of type 2 alveolar epithelial cell depletion
      produce characteristic injury repair outcomes. Most importantly, use of these
      mice will contribute to a better understanding of the role of AEC2 in the
      initiation of, and response to, lung injury. 

PMID- 26203801
TI  - Watch the weathercock: changes in re-staging 18F-FDG PET/CT scan predict the
      probability of relapse in locally advanced non-small cell lung cancer.
AB  - INTRODUCTION: Induction treatment is be coming the gold standard for locally
      advanced non-small cell lung cancers (LA-NSCLC). In contrast to baseline positron
      emission/computed tomography scan (PET/CT scan), re-staging PET/CT scan has been
      poorly studied in LA-NSCLC. MATERIALS AND METHODS: We retrospectively explored
      the efficacy of re-staging PET/CT scan to diagnose response and to predict
      disease-free survival (DFS) in 55 induction-treated LA-NSCLC further treated with
      curative surgery or radiation but not with adjuvant therapy. RESULTS: Re-staging
      N status by PET/CT scan significantly correlated with pathological N status.
      Radiological or metabolic response in the re-staging PET/CT scan was associated
      with a significantly better DFS, which decreased from 25.8 to 19.3, to 11.2, and
      to 9.4 months in cN0, cN1, cN2, and cN3 patients, respectively. CONCLUSION: Re
      staging PET/CT scan helps to define response and consolidation treatment in
      induction-treated LA-NSCLC and predicts DFS. Further extended studies should
      confirm our results.

PMID- 26203803
TI  - Silicon-containing nanocarriers for targeted drug delivery: synthesis,
      physicochemical properties and acute toxicity.
AB  - Silicon-containing nanoparticles (NPs) are considered promising drug carriers for
      targeted drug delivery. In this study, we investigated the physical and chemical
      properties of silicon-containing NPs, including silica and organomodified silica
      NPs (SiO2NPs and OrSiO2NPs, respectively), with different surface modifications,
      with the aim of increasing drug-loading efficiency. In addition, we described the
      original synthesis methods of different sizes of OrSiO2NPs, as well as new hybrid
      OrSiO2NPs with a silica core (SiO2 + OrSiO2NPs). Animal experiments revealed that
      the silicon-containing NPs investigated were non-toxic, as evidenced by a lack of
      hemodynamic response after intravenous administration. Bioelimination studies
      showed rapid renal excretion of OrSiO2NPs. In drug release kinetics studies,
      adenosine was immobilized on SiO2NPs using three different approaches: physical
      adsorption, ionic, and covalent bonding. We observed that the rate of adenosine
      desorption critically depended on the type of immobilization; therefore,
      adenosine release kinetics can be adjusted by SiO2NP surface modification
      technique. Adsorption of adenosine on SiO2 + OrSiO2NPs resulted in a significant
      attenuation of adenosine-induced hypotension and bradycardia. 

PMID- 26203802
TI  - Twist as a new prognostic marker in hematological malignancies.
AB  - Twist proteins are members of basic helix-loop-helix family and are major
      regulators of embryogenesis. In adult humans, Twist proteins are mainly expressed
      in precursor cells, including myogenic, osteoblastic, chondroblastic and
      myelomonocytic lineages, maintaining their undifferentiated state. In addition,
      they play important roles in lymphocyte function and maturation. Recently,
      several studies have reported regulatory roles for Twist in the function and
      development of hematopoietic cells as well as in survival and development of
      numerous hematological malignancies. It is activated by numerous signal
      transduction pathways, including Akt, nuclear factor kappaB, Wnt, signal
      transducer and activator of transcription 3, mitogen-activated protein kinase and
      Ras signaling. Activated Twist has an anti-apoptotic role and protects cancer
      cells from apoptotic cell death. In addition, overexpression of Twist promotes
      the process of epithelial-mesenchymal transition, which has an essential role in
      cancer metastasis. Hereby, we review the aberrant expression of Twist in
      hematopoietic malignancies such as leukemias, lymphomas and myelodysplastic
      syndrome, which is related with poor prognosis and drug resistance in these
      disorders. Inactivation of Twist by small RNAs technology or chemotherapeutic
      inhibitors targeting Twist and upstream or downstream molecules of Twist
      signaling pathways may be helpful in management of disease to improve treatment
      strategies in malignancies.

PMID- 26203804
TI  - Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer,
      Including Age at Diagnosis.
AB  - BACKGROUND: Thyroid cancer is unique for having age as a staging variable.
      Recently, the commonly used age cut-point of 45 years has been questioned.
      OBJECTIVE: This study assessed alternate staging systems on the outcome of
      overall survival, and compared these with current National Thyroid Cancer
      Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular
      thyroid cancer. METHODS: A total of 4721 patients with differentiated thyroid
      cancer were assessed. Five potential alternate staging systems were generated at
      age cut-points in five-year increments from 35 to 70 years, and tested for model
      discrimination (Harrell's C-statistic) and calibration (R(2)). The best five
      models for papillary and follicular cancer were further tested with bootstrap
      resampling and significance testing for discrimination. RESULTS: The best five
      alternate papillary cancer systems had age cut-points of 45-50 years, with the
      highest scoring model using 50 years. No significant difference in C-statistic
      was found between the best alternate and current NTCTCS systems (p = 0.200). The
      best five alternate follicular cancer systems had age cut-points of 50-55 years,
      with the highest scoring model using 50 years. All five best alternate staging
      systems performed better compared with the current system (p = 0.003-0.035).
      There was no significant difference in discrimination between the best alternate
      system (cut-point age 50 years) and the best system of cut-point age 45 years (p
      = 0.197). CONCLUSIONS: No alternate papillary cancer systems assessed were
      significantly better than the current system. New alternate staging systems for
      follicular cancer appear to be better than the current NTCTCS system, although
      they require external validation.

PMID- 26203805
TI  - Dendritic Cells Differentiated from Human Umbilical Cord Blood-Derived Monocytes
      Exhibit Tolerogenic Characteristics.
AB  - Human umbilical cord blood (UCB) is rich in diverse hematopoietic stem cells that
      are competent to differentiate into various cell types with immunological
      compatibility at transplantation. Thus, UCB is a potential source for the
      preparation of dendritic cells (DCs) to be used for cell therapy against
      inflammatory disorders or cancers. However, the immunological properties of UCB
      derived DCs are not fully characterized. In this study, we investigated the
      phenotypes and functions of UCB monocyte-derived DCs (UCB-DCs) in comparison with
      those of adult peripheral blood (APB) monocyte-derived DCs (APB-DCs). UCB-DCs
      contained less CD1a(+) DCs, which is known as immunostimulatory DCs, than APB
      DCs. UCB-DCs exhibited lower expression of CD80, MHC proteins, and DC-SIGN, but
      higher endocytic activity, than APB-DCs. Lipopolysaccharide stimulation of UCB
      DCs minimally augmented the expression of maturation markers and production of
      interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha, but potently expressed
      IL-10. When UCB-DCs were cocultured with CD14(+) cell-depleted allogeneic
      peripheral blood mononuclear cells, they weakly induced the proliferation,
      surface expression of activation markers, and interferon (IFN)-gamma production
      of T lymphocytes compared with APB-DCs. UCB possessed higher levels of
      prostaglandin E2 (PGE2) than APB, which might be responsible for tolerogenic
      phenotypes and functions of UCB-DCs. Indeed, APB-DCs prepared in the presence of
      PGE2 exhibited CD1a(-)CD14(+) phenotypes with tolerogenic properties, including
      weak maturation, impaired IL-12 production, and negligible T lymphocyte
      activation as UCB-DCs did. Taken together, we suggest that UCB-DCs have
      tolerogenic properties, which might be due to PGE2 highly sustained in UCB. 

PMID- 26203807
TI  - Superconductivity emerging from a suppressed large magnetoresistant state in
      tungsten ditelluride.
AB  - The recent discovery of large magnetoresistance in tungsten ditelluride provides
      a unique playground to find new phenomena and significant perspective for
      potential applications. The large magnetoresistance effect originates from a
      perfect balance of hole and electron carriers, which is sensitive to external
      pressure. Here we report the suppression of the large magnetoresistance and
      emergence of superconductivity in pressurized tungsten ditelluride via high
      pressure synchrotron X-ray diffraction, electrical resistance, magnetoresistance
      and alternating current magnetic susceptibility measurements. Upon increasing
      pressure, the positive large magnetoresistance effect is gradually suppressed and
      turned off at a critical pressure of 10.5 GPa, where superconductivity
      accordingly emerges. No structural phase transition is observed under the
      pressure investigated. In situ high-pressure Hall coefficient measurements at low
      temperatures demonstrate that elevating pressure decreases the population of hole
      carriers but increases that of the electron ones. Significantly, at the critical
      pressure, a sign change of the Hall coefficient is observed. 

PMID- 26203811
TI  - A transferable anxiolytic placebo effect from noise to negative effect.
AB  - BACKGROUND: The placebo effect in relieving negative emotion arousal is poorly
      understood. AIMS: We examined whether placebo expectation established with noise
      stimuli could have a transferable anxiolytic effect on negative emotion arousal.
      METHODS: In Experiment 1, noise intensity was surreptitiously lowered during
      placebo condition in the preconditioning phase to reinforce placebo expectation,
      and the noise-relieving placebo effect was assessed in the testing phase. In
      Experiment 2, the same manipulation as in Experiment 1 was administered in the
      preconditioning phase, but the anxiolytic placebo effect was assessed in the
      testing phase using negative pictures. RESULTS: Intensity and annoyance by the
      noise in Experiment 1 were significantly reduced, and unpleasantness in
      Experiment 2 was also significantly reduced in the placebo condition. CONCLUSION:
      Direct noise-relieving placebo effects and transferred anxiolytic placebo effects
      were found. The present study provides evidence that the placebo effect can be
      transferred from noise to emotion.

PMID- 26203812
TI  - Erratum, Vol. 12, March 26 Release.

PMID- 26203813
TI  - Community Engagement in Health-Related Research: A Case Study of a Community
      Linked Research Infrastructure, Jefferson County, Arkansas, 2011-2013.
AB  - BACKGROUND: Underrepresentation of racial minorities in research contributes to
      health inequities. Important factors contributing to low levels of research
      participation include limited access to health care and research opportunities,
      lack of perceived relevance, power differences, participant burden, and absence
      of trust. We describe an enhanced model of community engagement in which we
      developed a community-linked research infrastructure to involve minorities in
      research both as participants and as partners engaged in issue selection, study
      design, and implementation. COMMUNITY CONTEXT: We implemented this effort in
      Jefferson County, Arkansas, which has a predominantly black population, bears a
      disproportionate burden of chronic disease, and has death rates above state and
      national averages. METHODS: Building on existing community-academic partnerships,
      we engaged new partners and adapted a successful community health worker model to
      connect community residents to services and relevant research. We formed a
      community advisory board, a research collaborative, a health registry, and a
      resource directory. OUTCOME: Newly formed community-academic partnerships
      resulted in many joint grant submissions and new projects. Community health
      workers contacted 2,665 black and 913 white community residents from December
      2011 through April 2013. Eighty-five percent of blacks and 88% of whites were
      willing to be re-contacted about research of potential interest. Implementation
      challenges were addressed by balancing the needs of science with community needs
      and priorities. INTERPRETATION: Our experience indicates investments in community
      linked research infrastructure can be fruitful and should be considered by
      academic health centers when assessing institutional research infrastructure
      needs.

PMID- 26203815
TI  - Assessing Child Obesity and Physical Activity in a Hard-to-Reach Population in
      California's Central Valley, 2012-2013.
AB  - INTRODUCTION: In California's agricultural Central Valley, the rate of childhood
      obesity is higher than the national average. Adequate physical activity
      contributes to obesity prevention and its assessment is useful to evaluate the
      impact of interventions. METHODS: Ninos Sanos, Familia Sana (Healthy Children,
      Healthy Family [NSFS]) uses community-based participatory research to implement
      an intervention program to reduce childhood obesity among people of Mexican
      origin in the Central Valley. Anthropometric measurements were conducted on more
      than 650 children enrolled in NSFS. Physical activity data from a subgroup of
      children aged 4 to 7 years (n = 134) were collected via a wearable accelerometer.
      RESULTS: Children were classified on the basis of age and sex-adjusted body mass
      index as healthy weight (57.7%); overweight (19.3%), or obese (23%). Logistic
      regression showed that moderate to vigorous physical activity (MVPA) was
      associated with a child's likelihood of having a healthy BMI (odds ratio: 1.03;
      95% CI, 1.01-1.05; P = .017). CONCLUSION: NSFS's community-based participatory
      approach resulted in successful use of a commercial electronic device to measure
      physical activity quantity and quality in this hard-to-reach population.
      Promotion of adequate daily MVPA is an appropriate and necessary component of
      NSFS's childhood obesity prevention strategy.

PMID- 26203814
TI  - Lasting Effects of the Breast and Cervical Cancer Early Detection Program on
      Breast Cancer Detection and Outcomes, Ohio, 2000-2009.
AB  - INTRODUCTION: The National Breast and Cervical Cancer Early Detection Program
      (BCCP) in Ohio provides screening and treatment services for uninsured low-income
      women aged 40 to 64. Because participation in the BCCP might engender greater
      self-efficacy for cancer screening, we hypothesized that breast cancer and
      survival outcomes would be better in BCCP participants who become age-eligible to
      transition to Medicare than in their low-income non-BCCP counterparts. METHODS:
      Linking data from the 2000 through 2009 Ohio Cancer Incidence Surveillance System
      with the BCCP database, Medicare files, Ohio death certificates (through 2010),
      and the US Census, we identified Medicare beneficiaries who were aged 66 to 74
      and diagnosed with incident invasive breast cancer. We compared the following
      outcomes between BCCP women (n = 93) and low-income non-BCCP women (n = 420):
      receipt of screening mammography in previous year, advanced-stage disease at
      diagnosis, timely and standard care, all-cause survival, and cancer survival. We
      conducted multivariable logistic regression and survival analysis to examine the
      association between BCCP status and each of the outcomes, adjusting for patient
      covariates. RESULTS: Women who participated in the BCCP were nearly twice as
      likely as low-income non-BCCP women to have undergone screening mammography in
      the previous year (adjusted odds ratio, 1.77; 95% confidence interval, 1.01
      3.09). No significant differences were detected in any other outcomes.
      CONCLUSION: With the exception of screening mammography, the differences in
      outcomes were not significant, possibly because of the small size of the study
      population. Future analysis should be directed toward identifying the factors
      that explain these findings.

PMID- 26203817
TI  - In vitro studies on the stability in the proximal gastrointestinal tract and
      bioaccessibility in Caco-2 cells of chlorogenic acids from spent coffee grounds.
AB  - Spent coffee grounds are a potential commercial source of substantial amounts of
      chlorogenic acids (CGAs). The aim of this study was to evaluate the stability of
      spent coffee CGAs using in vitro simulated gastroduodenal digestion and to
      investigate their potential absorption using an in vitro Caco-2 model of human
      small intestinal epithelium. During in vitro digestion, lactones were partially
      degraded while caffeoylquinic and feruloylquinic acids were much more stable.
      Transport and metabolism studies showed that 1% of the total CGAs were absorbed
      and transported from the apical to the basolateral side of a Caco-2 cell
      monolayer after 1 h. Lactones and coumaroylquinic acids showed the rate of
      highest absorption. Caco-2 cells possessed low metabolic activity. In conclusion,
      spent coffee extracts contain large amounts of CGAs, which remained bioaccessible
      across the intestinal barrier, albeit to a relatively low degree. 

PMID- 26203816
TI  - Factors Associated With Adherence to Blood Pressure Measurement Recommendations
      at Pediatric Primary Care Visits, Minnesota and Colorado, 2007-2010.
AB  - INTRODUCTION: Elevated blood pressure in childhood may predict increased
      cardiovascular risk in young adulthood. The Task Force on the Diagnosis,
      Evaluation and Treatment of High Blood pressure in Children and Adolescents
      recommends that blood pressure be measured in children aged 3 years or older at
      all health care visits. Guidelines from both Bright Futures and the Expert Panel
      of Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children
      and Adolescents recommend annual blood pressure screening. Adherence to these
      guidelines is unknown. METHODS: We conducted a cross-sectional study to assess
      compliance with blood pressure screening recommendations in 2 integrated health
      care delivery systems. We analyzed electronic health records of 103,693 subjects
      aged 3 to 17 years. Probability of blood pressure measurement documented in the
      electronic health record was modeled as a function of visit type (well-child vs
      nonwell-child); patient age, sex, race/ethnicity, and body mass index; health
      care use; insurance type; and type of office practice or clinic department
      (family practice or pediatrics). RESULTS: Blood pressure was measured at 95% of
      well-child visits and 69% of nonwell-child outpatient visits. After adjusting for
      potential confounders, the percentage of nonwell-child visits with measurements
      increased linearly with patient age (P < .001). Overall, the proportion of
      children with annual blood pressure measurements was high and increased with age.
      Family practice clinics were more likely to adhere to blood pressure measurement
      guidelines compared with pediatric clinics (P < .001). CONCLUSION: These results
      show good compliance with recommendations for routine blood pressure measurement
      in children and adolescents. Findings can inform the development of EHR-based
      clinical decision support tools to augment blood pressure screening and
      recognition of prehypertension and hypertension in pediatric patients.

PMID- 26203818
TI  - Autonomic Nervous System and Outcome after Neuro-Rehabilitation in Disorders of
      Consciousness.

PMID- 26203819
TI  - Pleiotropy across academic subjects at the end of compulsory education.
AB  - Research has shown that genes play an important role in educational achievement.
      A key question is the extent to which the same genes affect different academic
      subjects before and after controlling for general intelligence. The present study
      investigated genetic and environmental influences on, and links between, the
      various subjects of the age-16 UK-wide standardized GCSE (General Certificate of
      Secondary Education) examination results for 12,632 twins. Using the twin method
      that compares identical and non-identical twins, we found that all GCSE subjects
      were substantially heritable, and that various academic subjects correlated
      substantially both phenotypically and genetically, even after controlling for
      intelligence. Further evidence for pleiotropy in academic achievement was found
      using a method based directly on DNA from unrelated individuals. We conclude that
      performance differences for all subjects are highly heritable at the end of
      compulsory education and that many of the same genes affect different subjects
      independent of intelligence. 

PMID- 26203820
TI  - Cyclocarya paliurus prevents high fat diet induced hyperlipidemia and obesity in
      Sprague-Dawley rats.
AB  - Cyclocarya paliurus (CP; qing qian liu), which is used as an herbal tea in China,
      has been confirmed to have therapeutic effects on hyperlipidemia and obesity, and
      therefore it is widely consumed to prevent metabolic diseases such as
      hyperlipidemia and diabetes. In this study, we investigated the preventive
      effects of CP on obesity and hyperlipidemia, as well as the underlying mechanisms
      involved in intestinal secretion of apolipoprotein (apo) B48. Sprague-Dawley rats
      were fed a high-fat diet (HFD) and with or without various concentrations of an
      ethanol extract of CP (CPE; 2, 4, or 8 g.(kg body mass)(-1)) administered by
      gavage for 8 weeks. From the results we see that CPE dose-dependently blocked
      increases in body mass, and decreased food utilization as well as visceral fat
      mass. Decreased serum levels of total cholesterol, triglycerides, and low density
      lipoprotein cholesterol, and elevated levels of high density lipoprotein
      cholesterol, as well as lowered levels of total cholesterol and triglycerides in
      the liver were also noticed in CPE-treated rats. Magnetic resonance images
      indicated that the abnormal fat storage induced by the HFD was obviously
      suppressed by CPE. In addition, ELISA analysis showed reduced fasting serum
      apoB48 in the CPE treatment groups. Based on the above results, CPE shows a
      promising preventive effect on obesity and hyperlipidemia, partially through
      suppressing intestinal apoB48 overproduction.

PMID- 26203821
TI  - Preparation of plants for developmental and cellular imaging by light-sheet
      microscopy.
AB  - Long-term fluorescence live-cell imaging experiments have long been limited by
      the effects of excitation-induced phototoxicity. The advent of light-sheet
      microscopy now allows users to overcome this limitation by restricting excitation
      to a narrow illumination plane. In addition, light-sheet imaging allows for high
      speed image acquisition with uniform illumination of samples composed of multiple
      cell layers. The majority of studies conducted thus far have used custom-built
      platforms with specialized hardware and software, along with specific sample
      handling approaches. The first versatile commercially available light-sheet
      microscope, Lightsheet Z.1, offers a number of innovative solutions, but it
      requires specific strategies for sample handling during long-term imaging
      experiments. There are currently no standard procedures describing the
      preparation of plant specimens for imaging with the Lightsheet Z.1. Here we
      describe a detailed protocol to prepare plant specimens for light-sheet
      microscopy, in which Arabidopsis seeds or seedlings are placed in solid medium
      within glass capillaries or fluorinated ethylene propylene tubes. Preparation of
      plant material for imaging may be completed within one working day.

PMID- 26203822
TI  - Superresolution live imaging of plant cells using structured illumination
      microscopy.
AB  - Although superresolution (SR) approaches have been routinely used for fixed or
      living material from other organisms, the use of time-lapse structured
      illumination microscopy (SIM) imaging in plant cells still remains under
      developed. Here we describe a validated method for time-lapse SIM that focuses on
      cortical microtubules of different plant cell types. By using one of the existing
      commercially available SIM platforms, we provide a user-friendly and easy-to
      follow protocol that may be widely applied to the imaging of plant cells. This
      protocol includes steps describing calibration of the microscope and channel
      alignment, generation of an experimental point spread function (PSF), preparation
      of appropriate observation chambers with available plant material, image
      acquisition, reconstruction and validation. This protocol can be carried out
      within two to three working days.

PMID- 26203823
TI  - An orthotopic mouse model of hepatocellular carcinoma with underlying liver
      cirrhosis.
AB  - Subcutaneous xenografts have been used for decades to study hepatocellular
      carcinoma (HCC). These models do not reproduce the specific pathophysiological
      features of HCCs, which occur in cirrhotic livers that show pronounced
      necroinflammation, abnormal angiogenesis and extensive fibrosis. As these
      features are crucial for studying the role of the pathologic host
      microenvironment in tumor initiation, progression and treatment response,
      alternative HCC models are desirable. Here we describe a syngeneic orthotopic HCC
      model in immunocompetent mice with liver cirrhosis induced by carbon
      tetrachloride (CCl4) that recapitulates key features of human HCC. Induction of
      substantial hepatic fibrosis requires 12 weeks of CCl4 administration.
      Intrahepatic implantation of mouse HCC cell lines requires 30 min per mouse.
      Tumor growth varies by tumor cell line and mouse strain used. Alternatively,
      tumors can be induced in a genetically engineered mouse model. In this setting,
      CCl4 is administered for 12 weeks after tail-vein injection of Cre-expressing
      adenovirus (adeno-Cre) in Stk4(-/-)Stk3(F/-) (also known as Mst1(-/-)Mst2(F/-); F
      indicates a floxed allele) mice, and it results in the development of HCC tumors
      (hepatocarcinogenesis) concomitantly with liver cirrhosis.

PMID- 26203824
TI  - Screening high-risk children for asthma through a community intervention.
AB  - OBJECTIVE: Many children, particularly those from inner city neighborhoods, have
      undiagnosed asthma. This study was done to evaluate the effectiveness of an
      asthma screening, referral and follow-up intervention in an inner city community
      setting in early identification of children at risk for undiagnosed asthma.
      METHODS: A descriptive longitudinal cohort design was used to assess children at
      baseline and at a 2-year follow-up. Parents of children in a private day school
      and a church Sunday school (N = 103) completed a validated Asthma Screening Tool
      at both time periods. Children with asthma and at risk for asthma were referred
      to a primary care provider (PCP). RESULTS: At baseline, screening of 103
      children, ages 3-17 years (mean=7.7 +/- 2.9), were categorized as known asthma
      diagnosis (n = 22), at-risk for undiagnosed asthma (n = 52) and not at-risk for
      asthma (n = 29). Sixty-two (60.2%) parents responded to the 2-year follow-up.
      Referral to PCP was kept by 61.5% from the known asthma group and by 24% of
      children at-risk for asthma. At 2-year follow-up, among not at-risk group, no one
      converted to at risk status, but majority of children among known asthma group
      continued to have uncontrolled asthma symptoms, and very few received daily
      preventive asthma medications. CONCLUSIONS: The asthma screening, referral and
      follow-up intervention for inner city children in a community setting was
      successful in early identification of patients at-risk for asthma. More education
      for PCPs on guidelines for diagnosis and management of asthma is needed to
      decrease childhood asthma morbidity.

PMID- 26203825
TI  - Sequence variants on 17q21 are associated with the susceptibility of asthma in
      the population of Lahore, Pakistan.
AB  - OBJECTIVE: Single nucleotide polymorphisms (SNPs) on 17q21 are known to be
      associated with asthma disease in multiple populations. This study was designed
      to know whether this region is associated with asthma in Lahore region population
      or not. METHODS: A total of 200 asthma patients and 100 healthy controls were
      enrolled from different hospitals of Lahore, Pakistan. Twelve SNPs from
      chromosomal region 17q21 were analyzed in cases and controls by single base
      extension method and capillary-based genetic analyzers. Associations with asthma
      were checked using basic allelic model, genotypic model, and results were
      adjusted by logistic regression analysis using PLINK v1.9. Pair-wise linkage
      disequilibrium among the SNPs was analyzed by using Haploview software. RESULTS:
      SNP rs3816470 showed a strong association (p = 8.89 * 10(-5), Odd Ratio = 3.082
      [1.755-5.41]) with asthma, whereas rs3859192 and rs6503525 also showed a
      significant association with the development of asthma, especially in the case of
      positive family history. In LD block1 (93 kb) consisting of six SNPs (rs12936231,
      rs7216389, rs7216558, rs9894164, rs1007654 and rs7212938), none of the haplotypes
      show any significant association with asthma except the haplotype "CCTCAG", which
      is a significant protective factor against asthma having frequency 0.051 in
      controls while 0.017 in cases (p = 3.56 * 10(-2), chi2 = 4.415). CONCLUSION: The
      present study reports that the polymorphic genomic variant rs3816470 is
      significantly and independently associated with asthma in the studied population,
      while the variants, rs6503525 and rs3859192, also indicate a significant
      association with asthma in this population when family history of the disease is
      taken as a covariate.

PMID- 26203826
TI  - Efficacy and Safety of Tabalumab, an Anti-B-Cell-Activating Factor Monoclonal
      Antibody, in a Heterogeneous Rheumatoid Arthritis Population: Results From a
      Randomized, Placebo-Controlled, Phase 3 Trial (FLEX-O).
AB  - OBJECTIVES: The efficacy and safety of 2 different dosing regimens of tabalumab,
      a monoclonal antibody that neutralizes membrane-bound and soluble B-cell
      activating factor (BAFF), were evaluated in patients with rheumatoid arthritis.
      METHODS: In this phase 3, multicenter, randomized study, 1004 patients (intention
      to-treat population) received subcutaneous 120 mg tabalumab every 4 weeks
      (120/Q4W), 90 mg tabalumab every 2 weeks (90/Q2W), or placebo over 24 weeks. At
      baseline, a loading dose double the planned dose (ie, 240 mg, 180 mg, or placebo)
      was administered. Efficacy analyses were based on a prespecified subset of
      patients with 5 or more of 68 tender and 5 or more of 66 swollen joints at
      baseline (efficacy population, n = 849). The primary efficacy end point was ACR20
      (20% improvement in American College of Rheumatology criteria) response at week
      24. RESULTS: At week 24, there were no differences in ACR20 response rates
      (120/Q4W = 34.4%, 90/Q2W = 33.5%, placebo = 31.5%) or any other measures of
      efficacy across the treatment groups. Discontinuations due to adverse events (AE)
      were 3.4%, 2.7%, and 4.0%; incidence of treatment-emergent AEs were 64.1%, 58.2%,
      and 58.8%, with 23.2%, 25.9%, and 22.0% treatment-emergent infections; and
      incidence rates of serious AEs were 3.7%, 2.2%, and 2.8% with 1.1%, 0.3%, and
      0.7% serious infections in the 120/Q4W, 90/Q2W, and placebo groups, respectively.
      Three deaths were reported (120/Q4W, n = 2; 90/Q2W, n = 1). Each tabalumab group
      had significant decreases versus placebo in CD3-CD20 B cells (P <= 0.05) and in
      serum immunoglobulins (P <= 0.001). CONCLUSIONS: Although tabalumab
      administration resulted in biologic activity, as demonstrated by changes in B
      cells and immunoglobulins, targeting BAFF-dependent pathways alone is not
      sufficient to significantly reduce rheumatoid arthritis disease activity.

PMID- 26203827
TI  - Development of a Multidimensional Additive Points System for Determining Access
      to Rheumatology Services.
AB  - OBJECTIVE: In many countries, including New Zealand, the demand for rheumatology
      services exceeds their supply, resulting in some patients experiencing long
      delays or being denied access. The principal aim of this work was to create a
      validated, transparent, and fair system for determining access to rheumatology
      services. METHODS: A panel of 5 rheumatologists, 6 primary care physicians, and 4
      nurse specialists ranked a series of 25 clinical scenarios in order of priority
      to see a rheumatologist. Important determining factors were weighted in an
      iterative process to generate a multidimensional additive point score to
      determine access to rheumatology service. RESULTS: The score comprises 6 domains
      of 2 to 4 items weighted to give a total score out of 100. The effect of the
      problem on the patient's life and role, the presence of an inflammatory rheumatic
      disease, appropriateness of current treatment, and the ability of the
      rheumatologist to influence the current symptoms and future prognosis were felt
      to be critical factors in determining access to the service. The score showed a
      strong correlation with the rankings agreed by the clinical panel, and the
      overall intraclass correlation coefficient for the rheumatologists was 0.698.
      CONCLUSIONS: Our score has face validity, is easy to perform, and has been
      assessed by an independent panel of rheumatologists as providing a fair system
      for determining access to rheumatology services. The system is acceptable to
      primary care physicians and has been adopted by our local primary care
      organizations.

PMID- 26203828
TI  - Efficacy and Safety of Rituximab in Systemic Lupus Erythematosus and Sjogren
      Syndrome Patients With Refractory Thrombocytopenia: A Retrospective Study of 21
      Cases.
AB  - OBJECTIVE: Recent studies suggested a potential of rituximab (RTX) in treating
      autoimmune thrombocytopenia (AITP) secondary to autoimmune diseases. In this
      study, we retrospectively evaluated the efficacy and safety of RTX therapy in
      patients with refractory AITP secondary to systemic lupus erythematosus (SLE) and
      Sjogren syndrome (SS). METHODS: Twenty-one SLE and/or SS patients with treatment
      resistant AITP were treated once or repeatedly with RTX at the Rheumatology
      Clinic Renji Hospital, during the period March 2012 to June 2014. Clinical and
      laboratory variables recorded at every follow-up visit were analyzed. RESULTS:
      The median age of all patients was 37.05 +/- 3.15 years (range, 13-67 years; 20
      female and 1 male). The median AITP duration before RTX treatment was 5.46 years.
      Previous treatments of 21 patients included immunosuppressive agents such as
      corticosteroids (n = 19), cyclosporine (n = 9), mycophenolate mofetil (n = 2),
      methotrexate (n = 3), cyclophosphamide (n = 2), vincristine (n = 3), and
      hydroxychloroquine (n = 15), and 7 patients received concomitantly intravenous
      immunoglobulin therapy. Two patients had undergone splenectomy without
      improvement. Seventeen patients (80.95%) were treated repeatedly with RTX during
      the follow-up period. The overall response rate to RTX treatment (including
      complete response, 52.38%; partial response, 28.57%) was 80.95%. A significant
      increase (P < 0.05) of platelet counts was seen after 1 month (median, 32.24 *
      10/mL vs 66.53 * 10/mL). Relapses occurred mostly during the first 9 months, and
      maintaining duration of response was 10.27 months (range, 2-17 months) on average
      after the first RTX infusion. Antiplatelet antibodies, especially IgG isotype,
      decreased significantly (P < 0.05) after RTX treatment. No adverse effects were
      observed among 15 patients (71.4%); however, 2 cases died of severe pneumonia,
      and another developed lymphoma. CONCLUSIONS: Rituximab is an additional potent
      therapeutic treatment option for SLE and SS patients with AITP refractory to
      conventional immunosuppressive treatments. For most patients, RTX was safe and
      well tolerated.

PMID- 26203829
TI  - Interarm Blood Pressure Difference in Patients With Systemic Lupus Erythematosus.
AB  - OBJECTIVES: This study was performed to determine the relationship between
      systemic lupus erythematosus (SLE) and the interarm blood pressure difference
      (IAD) and to elucidate the role of the IAD as a surrogate marker for early
      detection of peripheral artery disease (PAD) in patients with SLE. METHODS: In
      total, 135 patients with SLE and 135 age- and gender-matched subjects were
      enrolled. The IAD and risk of an abnormal IAD were compared between the SLE and
      control groups, and logistic regression analysis was performed to determine the
      relationship between SLE and an abnormal IAD. The specificity and sensitivity of
      an IAD of 10 mm Hg or greater for diagnosis of PAD (ankle brachial index of
      <0.90) were calculated. RESULTS: Both the systolic and diastolic IADs were
      significantly higher in the SLE group than in the control group (P < 0.001).
      After adjustment for confounding factors, SLE remained significantly associated
      with an abnormal IAD (P = 0.039). Both the systolic and diastolic IADs were
      negatively associated with the ankle brachial index. Using a systolic IAD of 10
      mm Hg or greater as the cutoff point, the specificity and sensitivity for PAD
      were 90% and 41%, respectively. A diastolic IAD of 10 mm Hg or greater exhibited
      higher specificity (92%), but lower sensitivity (30%). CONCLUSIONS: Systemic
      lupus erythematosus is independently associated with an abnormal IAD, and an IAD
      of 10 mm Hg or greater predicts PAD with high specificity but low sensitivity.
      Blood pressure should be measured at least once in both arms in patients with SLE
      for early detection of asymptomatic PAD.

PMID- 26203830
TI  - Determinants of Patient Satisfaction in an Academic Rheumatology Practice.
AB  - BACKGROUND: Although patient satisfaction is used as a measure of physician
      performance and is an essential component of chronic disease management, there is
      limited understanding about factors affecting satisfaction in rheumatologic
      settings. OBJECTIVE: Our study aimed to identify factors affecting satisfaction
      in outpatients with rheumatic diseases by correlating satisfaction with various
      factors. METHODS: We conducted a cross-sectional cohort study of rheumatology
      patients at Oregon Health & Science University in 2013. Patient satisfaction
      ratings were obtained, and data were collected from medical records. Descriptive
      and quantile regression analyses were performed to describe the population and to
      model predictors of satisfaction. RESULTS: We obtained data from 573 patients,
      76% were females, 92% were non-Hispanic white, with a mean age of 50 (SD, 15)
      years. Female gender (beta = 7.51; 95% confidence interval [CI], 6.16-8.86),
      older age (beta = 0.10; 95% CI, 0.01-0.20), and follow-up visit (beta = 4.04; 95%
      CI, 0.14-7.93) had a positive impact on satisfaction, whereas polymyalgia
      rheumatica (beta = -9.25; 95% CI, -15.25 to -3.25), arthralgia (beta = -8.67; 95%
      CI, -16.60 to -0.74), myalgia (beta = -8.67; 95% CI, -16.60 to -0.74), gout (beta
      = -7.5; 95% CI, -14.13 to -0.89), ankylosing spondylitis (beta = -5.20; 95% CI, 
      9.65 to -0.75), pain (beta = -4.62; 95% CI, -8.43 to -0.81), fibromyalgia (beta =
      -4.62; 95% CI, -7.80 to -1.44), longer visit duration (beta = -0.08; 95% CI, 
      0.13 to -0.03), and afternoon appointments (beta = -4.62; 95% CI, -7.04 to -2.20)
      had an inverse effect. CONCLUSIONS: Factors contributing to satisfaction scores
      differed for median satisfaction level and lower satisfaction level. Most of the
      factors identified as influencing patient satisfaction were unrelated to the
      physician or the skills of that physician.

PMID- 26203831
TI  - Pirouetting Away the Pain With Music.

PMID- 26203832
TI  - Recovery of Severe Muscular and Fascial Calcinosis After Treatment With
      Bisphosphonates in a Child With Juvenile Dermatomyositis.
AB  - Juvenile dermatomyositis (JDM) is a serious systemic autoimmune condition
      primarily affecting proximal muscles and skin, which is frequently associated
      with calcinosis. We report a case of a 10-year-old boy with JDM and severe
      calcification deposits along fasciae and muscle planes. He complained of symptoms
      associated to JDM with pulmonary involvement since 1 year before receiving
      medical attention. Three months before consultation, he experienced bilateral leg
      pain accompanied by progressive hardening of muscles and the presence of small
      nodules around the elbows and submandibular region. Computed tomography images
      revealed a severe "eggshell" calcification pattern of the lower-limb muscular
      fasciae. Significant clinical and radiological improvement was achieved after 30
      months of alendronate therapy. 

PMID- 26203834
TI  - Lofgren Syndrome Misdiagnosed as Lower-Extremity Cellulitis.

PMID- 26203833
TI  - Calcium Pyrophosphate Deposition Pseudoabscess.

PMID- 26203836
TI  - Hypocomplementemic Urticarial Vasculitis Syndrome Possibly Secondary to
      Etanercept Use.

PMID- 26203837
TI  - Vitamin D Levels and Associations With Disease Activity in Chinese Han Patients
      With Early Rheumatoid Arthritis.

PMID- 26203838
TI  - Granulomatous Mastitis Heralding the Onset of Full-Blown Granulomatosis With
      Polyangiitis.

PMID- 26203839
TI  - Surgical Treatment of Knee and Ankle Joint Contractures Resulting From Chronic
      Tophaceous Gout.

PMID- 26203840
TI  - ?

PMID- 26203841
TI  - ?

PMID- 26203843
TI  - ?

PMID- 26203842
TI  - ?

PMID- 26203844
TI  - ?

PMID- 26203845
TI  - ?

PMID- 26203846
TI  - ?

PMID- 26203849
TI  - Outcome measurement of refractory breathlessness: endpoints and important
      differences.
AB  - PURPOSE OF REVIEW: Standardized measurement of self-rated breathlessness using
      appropriate tools is essential for research and clinical care. The purpose was to
      review recent advances in the measurement of breathlessness and the minimal
      clinically important differences (MCIDs) in intensity of chronic breathlessness.
      RECENT FINDINGS: Two tools have been validated in people with chronic obstructive
      pulmonary disease (COPD) to measure daily symptoms and breathlessness related to
      daily activities. Two multidimensional tools have been developed for different
      settings and aetiologies, which measure both the perceived intensity,
      unpleasantness, quality of breathlessness, and the person's emotional response to
      it. MCIDs have been reported for the intensity of chronic refractory
      breathlessness, the daily symptom diary, and breathlessness related to daily
      activities in COPD. SUMMARY: There have been substantial developments in
      instruments able to provide reliable and valid unidimensional and
      multidimensional measurement of self-reported breathlessness and in the
      understanding of the MCID for chronic breathlessness. Routine use of agreed
      outcome measures in clinical practice and research are crucial steps to improve
      our understanding of the science of breathlessness and its impact on patients'
      outcomes.

PMID- 26203851
TI  - A new era of therapy for hepatitis C virus infection.
AB  - PURPOSE OF REVIEW: Previous treatments with pegylated interferon (PEG-IFN) and
      ribavirin for hepatitis C virus (HCV) infection resulted in significant adverse
      events and low cure rates, even with the addition of first-generation protease
      inhibitors. The standard of care for chronic HCV infection changed dramatically
      in 2013 with the approval of second-generation direct-acting antivirals, which
      led the way for IFN-free combination regimens. RECENT FINDINGS: All-oral
      combinations of direct-acting antivirals, with or without ribavirin, have shown
      high efficacy and are well tolerated in patients with the predominant genotypes,
      advanced fibrosis stages, and HIV co-infection. New fixed-dose co-formulations of
      direct-acting antivirals have allowed simpler regimens with shorter treatment
      durations and low rates of discontinuation, but are associated with substantial
      costs. SUMMARY: Since 2013, all-oral, IFN-free regimens with direct-acting
      antivirals have quickly become the mainstay of treatment for HCV infection as
      they provide high rates of sustained virologic response with a relatively short
      duration of treatment and low side-effect profile.

PMID- 26203850
TI  - Proprioceptive Training and Injury Prevention in a Professional Men's Basketball
      Team: A Six-Year Prospective Study.
AB  - Single limb stance instability is a risk factor for lower extremity injuries.
      Therefore, the development of proprioception may play an important role in injury
      prevention. This investigation considered a professional basketball team for 6
      years, integrating systematic proprioceptive activity in the training routine.
      The purpose was to assess the effectiveness of proprioceptive training programs
      based on quantifiable instability, to reduce ankle sprains, knee sprains, and low
      back pain through developing refined and long-lasting proprioceptive control.
      Fifty-five subjects were studied. In the first biennium (2004-2006), the
      preventive program consisted of classic proprioceptive exercises. In the second
      biennium (2006-2008), the proprioceptive training became quantifiable and
      interactive by means of electronic proprioceptive stations. In the third biennium
      (2008-2010), the intensity and the training volume increased while the session
      duration became shorter. Analysis of variance was used to analyze the differences
      in proprioceptive control between groups, years, and bienniums. Injury rates and
      rate ratios of injury during practices and games were estimated. The results
      showed a statistically significant reduction in the occurrence of ankle sprains
      by 81% from the first to the third biennium (p < 0.001). Low back pain showed
      similar results with a reduction of 77.8% (p < 0.005). The reduction in knee
      sprains was 64.5% (not significant). Comparing the third biennium with the level
      of all new entry players, proprioceptive control improved significantly by 72.2%
      (p < 0.001). These findings indicate that improvements in proprioceptive control
      in single stance may be a key factor for an effective reduction in ankle sprains,
      knee sprains, and low back pain.

PMID- 26203852
TI  - The use of posaconazole against Chagas disease.
AB  - PURPOSE OF REVIEW: The current therapeutic scenario against Chagas disease has
      been recently updated with the use of the triazoles in clinical trials and
      several experimental assays (in-vitro and in-vivo models) which are bringing
      novel and promising evidence for the treatment of Chagas diseases, mainly in its
      chronic phase. We pretend to analyze all the evidence extracted from the in-vitro
      and in-vivo assays, and try to understand the poor outcome of posaconazole (POS)
      in the clinical experience. RECENT FINDINGS: POS is the drug with more advanced
      development in both experimental model and clinical trial. Despite the promising
      results initially obtained in the animal model, the clinical trial did not meet
      expectations. Nevertheless, it has documented the activity against Trypanosoma
      cruzi either in the animal model or in humans. Also new treatment strategies,
      combination or sequential schemes, have been evaluated in the animal model.
      SUMMARY: POS has been tested in humans showing activity against T. cruzi, but not
      enough to reach cure by itself. Those results represent one of the most important
      breakthroughs in the treatment of Chagas disease, and open a window to new
      strategies as combination therapies or even sequential treatments.

PMID- 26203853
TI  - Hepatitis A: epidemiology in resource-poor countries.
AB  - PURPOSE OF REVIEW: Transmission of hepatitis A virus (HAV) infection is primarily
      fecal-oral. Symptomatic hepatitis, severe disease, and death are more likely to
      occur when infection occurs at an older age. Improvements in socioeconomic and
      hygienic conditions have led to a change in its epidemiology worldwide. RECENT
      FINDINGS: In the last two decades, improved hygiene in several resource-poor
      countries has led to reduced transmission of HAV, an increase in average age at
      infection, and, consequently, a paradoxical increase in morbidity and mortality
      because of hepatitis A. In Argentina, introduction of one dose (instead of the
      conventional two doses, to reduce costs) of inactivated HAV vaccine at 12-month
      age in a universal childhood immunization program during such 'epidemiologic
      transition' has markedly reduced the incidence of symptomatic hepatitis A, and of
      fulminant hepatitis and liver transplantation caused by HAV infection. The
      monetary value of medical and nonmedical benefits of this strategy outweighed the
      expenditure on vaccination. These excellent results were possibly contingent upon
      a high vaccination coverage. SUMMARY: Resource-poor countries should closely
      monitor the epidemiology of HAV infection and periodically undertake cost
      effectiveness analyses of HAV immunization strategies. This should allow timely
      identification of epidemiologic transition and introduction of preventive
      strategies before HAV infection becomes a public health problem.

PMID- 26203854
TI  - The epidemiology of non-polio enteroviruses: recent advances and outstanding
      questions.
AB  - PURPOSE OF REVIEW: There are over 100 serotypes of human enteroviruses, which
      cause a spectrum of illnesses, including meningitis, encephalitis, paralysis,
      myocarditis and rash. Increasing incidence of hand-foot-and-mouth disease in the
      Asia-Pacific region and recent outbreaks of enterovirus-associated disease, such
      as severe respiratory illness in the United States in 2014, highlight the threat
      of these viruses to human health. RECENT FINDINGS: We describe recent outbreaks
      of human enteroviruses and summarize knowledge gaps regarding their burden,
      spectrum of diseases and epidemiology. SUMMARY: Reported outbreaks of
      respiratory, neurological, skin and eye diseases associated with human
      enteroviruses have increased in frequency and size in recent years. Improved
      molecular diagnostics and genetic sequence analysis are beginning to reveal the
      complex dynamics of individual serotypes and genotypes, and their contribution to
      these outbreaks. However, the biological mechanisms underlying their emergence
      and transmission dynamics remain elusive. They are likely to involve changes in
      the virus, such as fitness, antigenicity, virulence or tropism, and in the human
      population, such as levels of sanitation and of homotypic and heterotypic
      immunity. Improvements in surveillance, serological surveys and detailed genetic
      and antigenic characterization of viral populations would help to elucidate these
      mechanisms. This will be important for the design of outbreak control and vaccine
      development strategies.

PMID- 26203855
TI  - Malaria diagnosis for malaria elimination.
AB  - PURPOSE OF REVIEW: Limitations of blood smear microscopy contributed to failure
      of the 1950-1960s WHO Global Programme to Eliminate Malaria. All diagnostic
      methods encounter limits of detection (LOD) beyond which it will not be possible
      to identify infected individuals. When this occurs, it becomes difficult to
      continue evaluating progress of malaria elimination. The purpose of this review
      is to compare available diagnostic technologies, factors that underlie their LOD,
      and their potential roles related to the goal of elimination. RECENT FINDINGS:
      Parasite-containing cells, parasite proteins, hemozoin, nucleic acids, and
      parasite-specific human antibodies are targets of diagnosis. Many studies report
      advantages of technologies to detect these diagnostic targets. Nucleic acid
      amplification tests and strategies for enriching capture of malaria diagnostic
      targets have consistently identified a parasite reservoir not detected by methods
      focused on the other biological targets. Exploiting magnetic properties of
      hemozoin may open new strategies for noninvasive malaria diagnosis. SUMMARY:
      Microscopy and rapid diagnostic tests provide effective surveillance for malaria
      control. Strategies that detect a reservoir of submicroscopic infection must be
      developed and standardized to guide malaria elimination.

PMID- 26203856
TI  - Perfusion Decellularization of Discarded Human Kidneys: A Valuable Platform for
      Organ Regeneration.

PMID- 26203857
TI  - Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and
      immune responses.
AB  - Acid sphingomyelinase (ASM), a lipid hydrolase enzyme, has the potential to
      modulate various cellular activation responses via the generation of ceramide and
      by interaction with cellular receptors. We have hypothesized that ASM modulates
      CD4(+) T-cell receptor activation and impacts immune responses. We first observed
      interactions of ASM with the intracellular domains of both CD3 and CD28. ASM
      further mediates T-cell proliferation after anti-CD3/CD28 antibody stimulation
      and alters CD4(+) T-cell activation signals by generating ceramide. We noted that
      various pharmacological inhibitors of ASM or knockdown of ASM using small hairpin
      RNA inhibit CD3/CD28-mediated CD4(+) T-cell proliferation and activation.
      Furthermore, such blockade of ASM bioactivity by biochemical inhibitors and/or
      molecular-targeted knockdown of ASM broadly abrogate T-helper cell responses. In
      conclusion, we detail immune, pivotal roles of ASM in adaptive immune T-cell
      responses, and propose that these pathways might provide novel targets for the
      therapy of autoimmune and inflammatory diseases. 

PMID- 26203858
TI  - Reciprocal positive regulation between Cx26 and PI3K/Akt pathway confers acquired
      gefitinib resistance in NSCLC cells via GJIC-independent induction of EMT.
AB  - Gefitinib efficiency in non-small-cell lung cancer (NSCLC) therapy is limited due
      to development of drug resistance. The molecular mechanisms of gefitinib
      resistance remain still unclear. In this study, we first found that connexin 26
      (Cx26) is the predominant Cx isoform expressed in various NSCLC cell lines. Then,
      two gefitinib-resistant (GR) NSCLC cell lines, HCC827 GR and PC9 GR, from their
      parental cells were established. In these GR cells, the results showed that
      gefitinib resistance correlated with changes in cellular EMT phenotypes and
      upregulation of Cx26. Cx26 was detected to be accumulated in the cytoplasm and
      failed to establish functional gap-junctional intercellular communication (GJIC)
      either in GR cells or their parental cells. Ectopic expression of GJIC-deficient
      chimeric Cx26 was sufficient to induce EMT and gefitinib insensitivity in HCC827
      and PC9 cells, while knockdown of Cx26 reversed EMT and gefitinib resistance in
      their GR cells both in vitro and in vivo. Furthermore, Cx26 overexpression could
      activate PI3K/Akt signaling in these cells. Cx26-mediated EMT and gefitinib
      resistance were significantly blocked by inhibition of PI3K/Akt pathway.
      Specifically, inhibition of the constitutive activation of PI3K/Akt pathway
      substantially suppressed Cx26 expression, and Cx26 was confirmed to functionally
      interplay with PI3K/Akt signaling to promote EMT and gefitinib resistance in
      NSCLC cells. In conclusion, the reciprocal positive regulation between Cx26 and
      PI3K/Akt signaling contributes to acquired gefitinib resistance in NSCLC cells by
      promoting EMT via a GJIC-independent manner. 

PMID- 26203859
TI  - Interactions between muscle stem cells, mesenchymal-derived cells and immune
      cells in muscle homeostasis, regeneration and disease.
AB  - Recent evidence has revealed the importance of reciprocal functional interactions
      between different types of mononuclear cells in coordinating the repair of
      injured muscles. In particular, signals released from the inflammatory infiltrate
      and from mesenchymal interstitial cells (also known as fibro-adipogenic
      progenitors (FAPs)) appear to instruct muscle stem cells (satellite cells) to
      break quiescence, proliferate and differentiate. Interestingly, conditions that
      compromise the functional integrity of this network can bias muscle repair toward
      pathological outcomes that are typically observed in chronic muscular disorders,
      that is, fibrotic and fatty muscle degeneration as well as myofiber atrophy. In
      this review, we will summarize the current knowledge on the regulation of this
      network in physiological and pathological conditions, and anticipate the
      potential contribution of its cellular components to relatively unexplored
      conditions, such as aging and physical exercise. 

PMID- 26203860
TI  - Genome-editing tools for stem cell biology.
AB  - Human pluripotent stem cells provide a versatile platform for regenerative
      studies, drug testing and disease modeling. That the expression of only four
      transcription factors, Oct4, Klf4, Sox2 and c-Myc (OKSM), is sufficient for
      generation of induced pluripotent stem cells (iPSCs) from differentiated somatic
      cells has revolutionized the field and also highlighted the importance of OKSM as
      targets for genome editing. A number of novel genome-editing systems have been
      developed recently. In this review, we focus on successful applications of
      several such systems for generation of iPSCs. In particular, we discuss genome
      editing systems based on zinc-finger fusion proteins (ZFs), transcription
      activator-like effectors (TALEs) and an RNA-guided DNA-specific nuclease, Cas9,
      derived from the bacterial defense system against viruses that utilizes clustered
      regularly interspaced short palindromic repeats (CRISPR). 

PMID- 26203861
TI  - Sigma-1 receptor deficiency reduces MPTP-induced parkinsonism and death of
      dopaminergic neurons.
AB  - Sigma-1 receptor (sigma1R) has been reported to be decreased in nigrostriatal
      motor system of Parkinson's disease patients. Using heterozygous and homozygous
      sigma1R knockout (sigma1R+/- and sigma1R-/-) mice, we investigated the influence
      of sigma1R deficiency on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      impaired nigrostriatal motor system. The injection of MPTP for 5 weeks in wild
      type mice (MPTP-WT mice), but not in sigma1R+/- or sigma1R-/- mice (MPTP
      sigma1R+/- or MPTP-sigma1R-/- mice), caused motor deficits and ~40% death of
      dopaminergic neurons in substantia nigra pars compacta with an elevation of N
      methyl-d-aspartate receptor (NMDAr) NR2B phosphorylation. The sigma1R antagonist
      NE100 or the NR2B inhibitor Ro25-6981 could alleviate the motor deficits and the
      death of dopaminergic neurons in MPTP-WT mice. By contrast, MPTP-sigma1R+/- mice
      treated with the sigma1R agonist PRE084 or MPTP-sigma1R-/- mice treated with the
      NMDAr agonist NMDA appeared to have similar motor deficits and loss of
      dopaminergic neurons as MPTP-WT mice. The pharmacological or genetic inactivation
      of sigma1R suppressed the expression of dopamine transporter (DAT) in substantia
      nigra, which was corrected by NMDA. The activation of sigma1R by PRE084 enhanced
      the DAT expression in WT mice or sigma1R+/- mice. By contrast, the level of
      vesicular monoamine transporter 2 (VMAT2) in sigma1R+/- mice or sigma1R-/- mice
      had no difference from WT mice. Interestingly, MPTP-WT mice showed the reduction
      in the levels of DAT and VMAT2, but MPTP-sigma1R-/- mice did not. The
      inactivation of sigma1R by NE100 could prevent the reduction of VMAT2 in MPTP-WT
      mice. In addition, the activation of microglia cells in substantia nigra was
      equally enhanced in MPTP-WT mice and MPTP-sigma1R-/- mice. The number of
      activated astrocytes in MPTP-sigma1R-/- mice was less than that in MPTP-WT mice.
      The findings indicate that the sigma1R deficiency through suppressing NMDAr
      function and DAT expression can reduce MPTP-induced death of dopaminergic neurons
      and parkinsonism.

PMID- 26203863
TI  - The Pulmonary Artery Catheter in 2015: The Swan and the Phoenix.
AB  - The pulmonary artery catheter (PAC) has revolutionized the care of critically ill
      patients by allowing physicians to directly measure important cardiovascular
      variables at the bedside. The relative ease of placement and the important
      physiological data obtained by PAC led to its incorporation as a central tool in
      the management of critically ill patients in intensive care units. Given the lack
      of demonstrable benefit in randomized clinical trials, persistent questions about
      safety, and recent advancements in noninvasive imaging modalities that purport to
      more accurately estimate cardiovascular hemodynamics, the use of the PAC has
      declined rapidly over recent years. Devised by cardiologists to measure
      hemodynamic parameters in patients with acute myocardial infarction, the PAC was
      quickly and enthusiastically adopted by intensivists, anesthesiologists,
      surgeons, and other specialists. This unbridled proliferation may have resulted
      in negative publicity surrounding the PAC. This article systematically reviews
      the evolution of PACs, the results of nonrandomized and randomized studies in
      various clinical conditions, the reasons for its decline, and current indications
      of PAC. 

PMID- 26203862
TI  - Activation of the SIRT1/p66shc antiapoptosis pathway via carnosic acid-induced
      inhibition of miR-34a protects rats against nonalcoholic fatty liver disease.
AB  - Recent studies have demonstrated that miR-34a expression is significantly
      upregulated and associated with apoptosis in nonalcoholic fatty liver disease
      (NAFLD). Carnosic acid (CA) is a novel antioxidant and a potential inhibitor of
      apoptosis in organ injury, including liver injury. This study aimed to
      investigate the signaling mechanisms underlying miR-34a expression and the
      antiapoptotic effect of CA in NAFLD. CA treatment significantly reduced the high
      fat diet (HFD)-induced elevations in aminotransferase activity as well as in
      serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein
      cholesterol (LDL-C) and malondialdehyde (MDA) levels but increased serum high
      density lipoprotein cholesterol (HDL-C) and hepatic superoxide dismutase (SOD)
      levels. Moreover, CA treatment ameliorated the increase in cleaved caspase-3
      caused by HFD exposure and completely reversed the HFD-induced decreases in
      manganese superoxide dismutase (MnSOD) and B-cell lymphoma-extra large
      expression. CA also counteracted the HFD- or palmitic acid (PA)-induced increases
      in caspase-3 and caspase-9 activity. Mechanistically, CA reversed the HFD- or PA
      induced upregulation of miR-34a, which is the best-characterized regulator of
      SIRT1. Importantly, the decrease in miR-34a expression was closely associated
      with the activation of the SIRT1/p66shc pathway, which attenuates hepatocyte
      apoptosis in liver ischemia/reperfusion injury. A dual luciferase assay in L02
      cells validated the modulation of SIRT1 by CA, which occurs at least partly via
      miR-34a. In addition, miR-34a overexpression was significantly counteracted by
      CA, which prevented the miR-34a-dependent repression of the SIRT1/p66shc pathway
      and apoptosis. Collectively, our results support a link between liver cell
      apoptosis and the miR-34a/SIRT1/p66shc pathway, which can be modulated by CA in
      NAFLD. 

PMID- 26203864
TI  - SNCA rs3822086 C>T Polymorphism Increases the Susceptibility to Parkinson's
      Disease in a Chinese Han Population.
AB  - OBJECTIVE: Protofibrils of alpha-synuclein mediate neuronal cell death and
      propagate Parkinson's disease (PD). In this study, we investigated the
      relationship between the rs3822086 C>T polymorphism located in the fourth intron
      of the alpha-synuclein (SNCA) gene and susceptibility to PD in a Chinese Han
      population. METHODS: 146 PD patients and 144 sex- and age-matched healthy
      individuals (control group) were selected for this study. The SNCA rs3822086
      polymorphism was examined in all 300 study subjects by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The
      genotype and allele frequencies of the SNCA rs3822086 polymorphism showed
      significant differences between the PD group and control group (TT: 25.3% vs.
      18.8%, p=0.035; CT+TT: 77.4% vs. 66.0%, p=0.031; T allele: 51.4% vs. 42.4%,
      p=0.030; respectively). Stratified analyses based on gender indicated that male
      PD patients exhibited higher genotype and allele frequencies of the SNCA
      rs3822086 polymorphism compared to healthy male controls (TT: 26.7% vs. 13.2%,
      p=0.011; CC+CT: 73.3% vs. 86.8%, p=0.024; T allele: 51.2% vs. 37.9%, p=0.012;
      respectively). Age-stratified analyses indicated that the genotype and allele
      frequencies of the SNCA rs3822086 polymorphism were significantly higher in PD
      patients older than 60 years in comparison to healthy controls (TT: 32.2% vs.
      20.5%, p=0.014; CT+TT: 77.0% vs. 60.2%, p=0.017; T allele: 54.6% vs. 40.3%,
      p=0.008; respectively). CONCLUSION: Our findings demonstrate that the SNCA
      rs3822086 C>T polymorphism correlates with increased susceptibility to PD among
      the Chinese Han population.

PMID- 26203865
TI  - On the role of humic acids' carboxyl groups in the binding of charged organic
      compounds.
AB  - Interactions of humic acids (HAs) with two cationic dyes (methylene blue and
      rhodamine 6G) were studied using a unique combination of diffusion and
      partitioning studies in HAs, containing hydrogels and batch sorption experiments.
      In order to investigate the involvement of carboxyl groups of HAs in these
      interactions, all experiments were performed for both, the original lignite HAs
      and HAs with selectively methylated carboxyls. The results of the diffusion
      experiments confirm that the interactions between the solute and humic substances
      have a strong impact on the rate of diffusion process. Surprisingly, the effect
      is almost equally approved for original and methylated HAs. On the other hand,
      the results of batch sorption experiments show strong improvement of the sorption
      capacity (methylated HAs), which is explained by changed morphology of alkylated
      HAs. The comparison of the results of diffusion and adsorption experiments shows
      that the diffusion experiments simulate the transport of solutes in natural
      humics containing environment more reasonably. 

PMID- 26203866
TI  - Perfluorinated compounds (PFCs) in the atmosphere of Shenzhen, China: Spatial
      distribution, sources and health risk assessment.
AB  - This study investigated the occurrence of perfluorinated compounds (PFCs) in the
      atmosphere of Shenzhen, China. 11 PFCs, including two perfluoroalkyl sulfonic
      acids (PFSAs, C6 and C8) and perfluoroalkyl carboxylic acids (PFCAs, C4-12) were
      determined by high performance liquid chromatography-negative electrospray
      ionization-tandem mass spectrometry (HPLC/ESI-MS/MS). Total PFC concentrations (?
      PFCs) in the atmospheric samples ranged from 3.4 to 34 pg m(-3) with an average
      of 15 pg m(-3). Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid
      (PFOS) were the two most abundant PFCs and on average accounted for 35% and 22%
      of ? PFCs, respectively. ? PFCs and total PFCA concentrations (? PFCAs) showed a
      tendency of low-lying East West, while the distribution of total PFSA
      concentrations (? PFSAs) was uniform. Higher concentrations of ? PFCs were found
      in Bao'an District which had very well-developed manufacturing industries. PCA
      model was employed to quantitatively calculate the contributions of sources. The
      results showed that PFOA-factor, long chain PFCs-factor and PFOS-factor were the
      three main source categories for PFCs in the atmosphere. Meanwhile, long-distance
      transport of pollutants from southeastern coastal areas might be another source
      of PFCs in Shenzhen atmosphere. PFCs in the atmosphere were more positively
      correlated with the levels PM10 than PM2.5, which indicated PFCs were more likely
      to adhere to particles with relatively large sizes. The hazard ratios of
      noncancer risk through breathing based on PFOS and PFOA concentrations were
      calculated and were less than unity, suggesting that PFCs concentrations may pose
      no or immediate threat to the residents in Shenzhen.

PMID- 26203867
TI  - Screening for over 1000 organic micropollutants in surface water and sediments in
      the Liaohe River watershed.
AB  - High throughout screening method has gained attractive prospects because it
      offers a fast and effective approach to obtain a holistic picture of organic
      micropollutant (OM) pollution in a site specific environment. However,
      reliability and usefulness of the generated data sets for OM pollution profiles
      and occurrence levels have not been fully evaluated. In this paper, we screened
      1030 OMs in surface water and sediments from the selected rivers of the Liaohe
      River watershed to (1) examine the usefulness of using qualitative data to gain
      insights into source identification and (2) further evaluate the reliability of
      the semi-quantification results in a filed study. The results showed that 81 and
      89 OMs at concentrations up to 5670 ng/L and 6714 ng/g were identified in surface
      water and sediments, respectively. Qualitative data could be used to identify the
      similarity (or dissimilarity) of pollution sources at different locations for
      surface water, which could provide insights for source back tracking of water
      contamination. Accuracy tests showed that our semi-quantification results agree
      well with those from previously reported values and our target analysis. Though
      our results for the majority of newly quantified OMs need to be further
      confirmed, we have demonstrated that this method is suitable for understanding
      the pollution characteristics and occurrence levels of OMs in the environment for
      environmental scientists and managers.

PMID- 26203868
TI  - Enhanced Immunostimulating Activity of Lactobacilli-Mimicking Materials by
      Controlling Size.
AB  - The design and synthesis of materials capable of activating the immune system in
      a safe manner is of great interest in immunology and related fields. Lactobacilli
      activate the innate immune system of a host when acting as probiotics. Here, we
      constructed lactobacilli-mimicking materials in which polysaccharide
      peptidoglycan complexes (PS-PGs) derived from lactobacilli were covalently
      conjugated to the surfaces of polymeric microparticles with a wide variety of
      sizes, ranging from 200 nm to 3 MUm. The artificial lactobacilli successfully
      stimulated macrophages without cytotoxicity. Importantly, we found that the size
      of artificial lactobacilli strongly influenced their immunostimulating
      activities, and that artificial lactobacilli of 1 MUm exhibited 10-fold higher
      activity than natural lactobacilli. One major advantage of the artificial
      lactobacilli is facile control of size, which cannot be changed in natural
      lactobacilli. These findings provide new insights into the design of materials
      for immunology as well as the molecular biology of lactobacillus. 

PMID- 26203870
TI  - Optically stimulated luminescence studies in combustion synthesized Al2O3:C,Cu,P.
AB  - A new Al2O3:C,Cu,P phosphor is developed by the combustion synthesis technique
      which exhibits entirely different OSL properties as compared to that of the
      commercial alumina. No thermoluminescence (TL) is observed in this phosphor which
      also differentiates the present phosphor from the commercially available Al2O3:C
      (Landauer). The phosphor shows good optically stimulated luminescence (OSL)
      sensitivity for ionizing radiation with a fast OSL decay as compared to the
      commercial Al2O3:C. The phosphor heated in air followed by heating under the
      reactive atmosphere exhibits maximum sensitivity amongst several other phosphors.
      On the basis of area integration method; integrated over initial 3s, the
      sensitivity of this phosphor is about 67% of that of commercial Al2O3:C. 

PMID- 26203869
TI  - Mapping Selective Inhibition of the Cancer-Related Carbonic Anhydrase IX Using
      Structure-Activity Relationships of Glucosyl-Based Sulfamates.
AB  - Inhibition of human carbonic anhydrase IX (hCA IX) has shown to be
      therapeutically advantageous for treating many types of highly aggressive
      cancers. However, designing selective inhibitors for hCA IX has been difficult
      due to its high structural homology and sequence similarity with off-target hCAs.
      Recently, the use of glucosyl sulfamate inhibitors has shown promise as selective
      inhibitors for hCA IX. In this study, we present five X-ray crystal structures,
      determined to a resolution of 1.7 A or better, of both hCA II (a ubiquitous CA)
      and an engineered hCA IX-mimic in complex with selected glucosyl sulfamates and
      structurally rationalize mechanisms for hCA IX selectivity. Results from this
      study have allowed us, for the first time, to empirically "map" key interactions
      of the hCA IX active site in order to establish parameters needed to design novel
      hCA IX selective inhibitors. 

PMID- 26203871
TI  - Portable x-ray fluorescence for assessing trace elements in rice and rice
      products: Comparison with inductively coupled plasma-mass spectrometry.
AB  - Portable x-ray fluorescence (XRF) was investigated as a means of assessing trace
      elements in rice and rice products. Using five measurement trials of 180 s real
      time, portable XRF was first used to detect arsenic (As), manganese (Mn), iron
      (Fe), nickel (Ni), copper (Cu), and zinc (Zn) in a variety of rice samples. The
      same samples were then microwave-digested and used to determine elemental
      concentrations using inductively coupled plasma-mass spectrometry (ICP-MS). The
      concentrations of As, Mn, Fe, Cu, and Zn determined by ICP-MS were found to be
      consistent with other recent studies involving various types of rice and rice
      products. When assessing for As, Mn, Fe, Cu, and Zn, comparison of results
      between XRF amplitude and ICP-MS concentration (wet weight) demonstrated a linear
      relationship with a significant correlation. A significant correlation between
      XRF amplitude and ICP-MS concentration was not found when assessing for Ni.

PMID- 26203872
TI  - Capacity factor analysis for evaluating water and sanitation infrastructure
      choices for developing communities.
AB  - 40% of the world's population lacks access to adequate supplies of water and
      sanitation services to sustain human health. In fact, more than 780 million
      people lack access to safe water supplies and about 2.5 billion people lack
      access to basic sanitation. Appropriate technology for water supply and
      sanitation (Watsan) systems is critical for sustained access to these services.
      Current approaches for the selection of Watsan technologies in developing
      communities have a high failure rate. It is estimated that 30%-60% of Watsan
      installed infrastructures in developing countries are not operating.
      Inappropriate technology is a common explanation for the high rate of failure of
      Watsan infrastructure, particularly in lower-income communities (Palaniappan et
      al., 2008). This paper presents the capacity factor analysis (CFA) model, for the
      assessment of a community's capacity to manage and sustain access to water supply
      and sanitation services. The CFA model is used for the assessment of a
      community's capacity to operate, and maintain a municipal sanitation service
      (MSS) such as, drinking water supply, wastewater and sewage treatment, and
      management of solid waste. The assessment of the community's capacity is based on
      seven capacity factors that have been identified as playing a key role in the
      sustainability of municipal sanitation services in developing communities (Louis,
      2002). These capacity factors and their constituents are defined for each
      municipal sanitation service. Benchmarks and international standards for the
      constituents of the CFs are used to assess the capacity factors. The assessment
      of the community's capacity factors leads to determine the overall community
      capacity level (CCL) to manage a MSS. The CCL can then be used to assist the
      community in the selection of appropriate Watsan technologies for their MSS
      needs. The selection is done from Watsan technologies that require a capacity
      level to operate them that matches the assessed CCL of the community. 

PMID- 26203873
TI  - Process optimization for Ni(II) removal from wastewater by calcined oyster shell
      powders using Taguchi method.
AB  - Waste oyster shells cause great environmental concerns and nickel is a harmful
      heavy metal. Therefore, we applied the Taguchi method to take care of both issues
      by optimizing the controllable factors for Ni(II) removal by calcined oyster
      shell powders (OSP), including the pH (P), OSP calcined temperature (T), Ni(II)
      concentration (C), OSP dose (D), and contact time (t). The results show that
      their percentage contribution in descending order is P (64.3%) > T (18.9%) > C
      (8.8%) > D (5.1%) > t (1.7%). The optimum condition is pH of 10 and OSP calcined
      temperature of 900  degrees C. Under the optimum condition, the Ni(II) can be
      removed almost completely; the higher the pH, the more the precipitation; the
      higher the calcined temperature, the more the adsorption. The latter is due to
      the large number of porosities created at the calcination temperature of 900 
      degrees C. The porosities generate a large amount of cavities which significantly
      increase the surface area for adsorption. A multiple linear regression equation
      obtained to correlate Ni(II) removal with the controllable factors is: Ni(II)
      removal(%) = 10.35 * P + 0.045 * T - 1.29 * C + 19.33 * D + 0.09 * t - 59.83.
      This equation predicts Ni(II) removal well and can be used for estimating Ni(II)
      removal during the design stage of Ni(II) removal by calcined OSP. Thus, OSP can
      be used to remove nickel effectively and the formula for removal prediction is
      developed for practical applications. 

PMID- 26203874
TI  - Novel Chryseobacterium sp. PYR2 degrades various organochlorine pesticides (OCPs)
      and achieves enhancing removal and complete degradation of DDT in highly
      contaminated soil.
AB  - Long term residues of organochlorine pesticides (OCPs) in soils are of great
      concerning because they seriously threaten food security and human health. This
      article focuses on isolation of OCP-degrading strains and their performance in
      bioremediation of contaminated soil under ex situ conditions. A bacterium,
      Chryseobacterium sp. PYR2, capable of degrading various OCPs and utilizing them
      as a sole carbon and energy source for growth, was isolated from OCP-contaminated
      soil. In culture experiments, PYR2 degraded 80-98% of hexachlorocyclohexane (HCH)
      or 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT) isomers (50 mg L(-1)) in
      30 days. A pilot-scale ex situ bioremediation study of highly OCP-contaminated
      soil augmented with PYR2 was performed. During the 45-day experimental period,
      DDT concentration was reduced by 80.3% in PYR2-augmented soils (35.37 mg kg(-1)
      to 6.97 mg kg(-1)) but by only 57.6% in control soils. Seven DDT degradation
      intermediates (metabolites) were detected and identified in PYR2-augmented soils:
      five by GC/MS: 1,1-dichloro-2,2-bis (4-chlorophenyl) ethane (DDD), 1,1-dichloro
      2,2-bis (4-chlorophenyl) ethylene (DDE), 1-chloro-2,2-bis (4-chlorophenyl)
      ethylene (DDMU), 1-chloro-2,2-bis (4-chlorophenyl) ethane (DDMS), and
      dichlorobenzophenone (DBP); and two by LC/MS: 4-chlorobenzoic acid (PCBA) and 4
      chlorophenylacetic acid (PCPA). Levels of metabolites were fairly stable in
      control soils but varied greatly with time in PYR2-augmented soils. Levels of
      DDD, DDMU, and DDE in PYR2-augmented soils increased from day 0 to day 30 and
      then decreased by day 45. A DDT biodegradation pathway is proposed based on our
      identification of DDT metabolites in PYR2-augmented systems. PYR2 will be useful
      in future studies of OCP biodegradation and in bioremediation of OCP-contaminated
      soils. 

PMID- 26203875
TI  - Filling gaps in a large reserve network to address freshwater conservation needs.
AB  - Freshwater ecosystems and biodiversity are among the most threatened at global
      scale, but efforts for their conservation have been mostly peripheral to
      terrestrial conservation. For example, Natura 2000, the world's largest network
      of protected areas, fails to cover adequately the distribution of rare and
      endangered aquatic species, and lacks of appropriate spatial design to make
      conservation for freshwater biodiversity effective. Here, we develop a framework
      to identify a complementary set of priority areas and enhance the conservation
      opportunities of Natura 2000 for freshwater biodiversity, using the Iberian
      Peninsula as a case study. We use a systematic planning approach to identify a
      minimum set of additional areas that would help i) adequately represent all
      freshwater fish, amphibians and aquatic reptiles at three different target
      levels, ii) account for key ecological processes derived from riverscape
      connectivity, and iii) minimize the impact of threats, both within protected
      areas and propagated from upstream unprotected areas. Addressing all these goals
      would need an increase in area between 7 and 46%, depending on the conservation
      target used and strength of connectivity required. These new priority areas
      correspond to subcatchments inhabited by endangered and range restricted species,
      as well as additional subcatchments required to improve connectivity among
      existing protected areas and to increase protection against upstream threats. Our
      study should help guide future revisions of the design of Natura 2000, while
      providing a framework to address deficiencies in reserve networks for adequately
      protecting freshwater biodiversity elsewhere. 

PMID- 26203876
TI  - Simultaneous removal of C and N from fish effluents in filter reactors: Effect of
      recirculation ratio on the axial distribution of microbial communities.
AB  - We simultaneously removed carbon (C) and nitrogen (N) from fish effluents in
      compact filter reactors operating at different recirculation ratios (RRs) (2, 10
      and without recirculation) to demonstrate microbial coexistence and determine the
      effect of the RR on the axial bacterial stratification. We also examined the
      global performance of anoxic, anaerobic and aerobic processes. Microbial
      communities (bacteria and archaea) were analyzed using 16s rRNA amplification
      followed by DGGE analyses. Their banding profiles were analyzed using ecological
      parameters and the most representative bands were sequenced. TOC removal was
      larger than 98% in the three reactors. The total N removal was 48% for the RR-2
      reactor, whereas in the RR-10 reactor, there was no N removal due to the absence
      of nitrification in the final aerobic step. Coexistence and stratification of
      microorganisms were observed. The microbial communities were correlated with
      distinct biochemical processes in each reactor fraction. The RR had a large
      effect on the distribution of the microbial communities. When the RR increased
      from 2 to 10, the stratification decreased from 60 to 30%, suggesting a close
      relationship between reactor performance and the presence of nitrifiers. In the
      RR-10 reactor, the nitrifier concentration was only 4%. Thus, in combined
      processes, filter reactors should operate with a moderate RR to favor bacterial
      stratification and improve performance. 

PMID- 26203877
TI  - Agri-environmental collaboratives as bridging organisations in landscape
      management.
AB  - In recent years, landscape and its management has become a focus of policies and
      academic conceptualisation. Landscape is understood as a concept of
      interconnected natural and human systems. Its management must take into account
      the dynamic interdependencies and diverging interests of various stakeholders at
      different levels. Bridging organisations can provide an arena for trust-building,
      conflict resolution, learning and collaboration between relevant stakeholders.
      This paper draws on two strands of literature - landscape governance and co
      management of social-ecological systems - to investigate the contributions of
      agri-environmental collaboratives (AEC) to sustainable landscape management.
      Based on data from 41 interviews with key informants and AEC members in Germany
      and the Netherlands, six fields of contributions were identified: policy
      implementation and service provision; coordination and mediation; awareness
      raising and behaviour change; care for 'everyday' landscapes; maintenance and
      protection of landscapes (including species and habitats); and income generation
      and economic benefits. Some of the contributions evolve around the specific role
      of AEC as bridging organisations, but other contributions such as economic
      benefits emerge beyond this analytical lens. The paper therefore emphasises
      holistic, bottom up assessment of AEC contributions and argues that governments
      should support such organisations through i) funding for facilitators and ii)
      funding for impact monitoring and data management. 

PMID- 26203878
TI  - General Stereodivergent Enantioselective Total Synthetic Approach toward
      Macrosphelides A-G and M.
AB  - A straightforward enantioselective total synthesis algorithm for the preparation
      of 8 out of 13 macrosphelides within 9-11 steps starting from tert-butyl sorbate
      is presented. The use of a cyclic sulfate as both protecting and reactivity
      directing group is the key element within this algorithm. A high-pressure
      transesterification allows for the selective ring-enlargement of the 15-membered
      macrosphelides into the 16-membered counterparts. The absolute configurations of
      the natural products were unambiguously assigned both by the chemical synthesis
      and by X-ray structure analysis. 

PMID- 26203879
TI  - Use of Close-Packed Vesicular Dispersions to Stabilize Colloidal Particle
      Dispersions against Sedimentation.
AB  - For many applications of colloidal dispersions, the particles must be suspended
      for a long time. This is often accomplished by preventing agglomeration, which
      generates aggregates of increasing size. Nevertheless, many colloidal dispersions
      of dense particles may settle even without agglomeration. Preventing
      sedimentation without significantly increasing the bulk dispersion viscosity is
      difficult and has received little attention in the literature. However, settling
      can be drastically reduced through the novel use of close-packed vesicular
      dispersions at high enough concentrations, which are non-Newtonian shear-thinning
      fluids. Such dispersions have much higher viscosities at the low shear stresses
      "felt" by sedimenting colloidal particles than at the high shear stresses
      relevant to bulk dispersion flow. In a practical example, dense TiO2
      nanoparticles which normally would settle rapidly can remain suspended for at
      least 6 months without any observable sedimentation when they are introduced into
      a close-packed vesicular dispersion, while the dispersion retains its
      flowability. Cryo-TEM images reveal that the vesicles in these dispersions are
      tightly close-packed. Dynamic light scattering and electrophoretic mobility data
      also confirm that the vesicles in such dispersions have very low mobilities. 

PMID- 26203881
TI  - Causes of mortality in green turtles from Hawaii and the insular Pacific
      exclusive of fibropapillomatosis.
AB  - Fibropapillomatosis (FP) comprises a majority of green turtle stranding in
      Hawaii; however, green turtles in the Pacific are also susceptible to non-FP
      related causes of death. We present here necropsy findings from 230 free-ranging
      green turtles originating from Hawaii, the Mariana archipelago, Palmyra Atoll,
      American Samoa, and Johnston Atoll that died from non-FP related causes. Most
      turtles died from fishing-induced or boat strike trauma followed by
      infectious/inflammatory diseases, nutritional problems (mainly cachexia), and an
      array of physiologic problems. Infectious/inflammatory problems included
      bacterial diseases of the lungs, eyes, liver or intestines, spirorchid fluke
      infection, or polyarthritis of unknown origin. Likelihood of a successful
      diagnosis of cause of death was a function of post-mortem decomposition.
      Fibropapillomatosis was not seen in turtles submitted from outside Hawaii. The
      preponderance of anthropogenic causes of mortality offers some management
      opportunities to mitigate causes of death in these animals by, for example,
      implementing measures to decrease boating and fishing interactions. 

PMID- 26203880
TI  - Increased harbor porpoise mortality in the Pacific Northwest, USA: understanding
      when higher levels may be normal.
AB  - In 2006, a marked increase in harbor porpoise Phocoena phocoena strandings were
      reported in the Pacific Northwest of the USA, resulting in the declaration of an
      unusual mortality event (UME) for Washington and Oregon to facilitate
      investigation into potential causes. The UME was in place during all of 2006 and
      2007, and a total of 114 porpoises stranded during this period. Responders
      examined 95 porpoises; of these, detailed necropsies were conducted on 75
      animals. Here we review the findings related to this event and how these compared
      to the years immediately before and after the UME. Relatively equal numbers among
      sexes and age classes were represented, and mortalities were attributed to a
      variety of specific causes, most of which were categorized as trauma or
      infectious disease. Continued monitoring of strandings during 4 yr following the
      UME showed no decrease in occurrence. The lack of a single major cause of
      mortality or evidence of a significant change or event, combined with high levels
      of strandings over several post-UME years, demonstrated that this was not an
      actual mortality event but was likely the result of a combination of factors,
      including: (1) a growing population of harbor porpoises; (2) expansion of harbor
      porpoises into previously sparsely populated areas in Washington's inland waters;
      and (3) a more well established stranding network that resulted in better
      reporting and response. This finding would not have been possible without the
      integrated response and investigation undertaken by the stranding network.

PMID- 26203882
TI  - Rhinosporidiosis in African reed frogs Hyperolius spp. caused by a new species of
      Rhinosporidium.
AB  - We report the identification of a new Rhinosporidium species (Dermocystida,
      Mesomycetozoea) infecting amphibian hosts, while showing a species specificity
      for African reed frogs of the genus Hyperolius. Large dermal cysts (sporangia) of
      R. rwandae sp. nov. were observed in 18% of H. lateralis and similar cysts in
      0.7% of H. viridiflavus surveyed. Fully developed R. rwandae cysts are about 500
      to 600 um in diameter and sealed from the frog tissue by a thick chitinous wall.
      Some cysts were filled with numerous round-oval basophilic microspores of 8 to 12
      um diameter. With the exception of legs, nodules were visible over the complete
      torso surface including the vocal sac of males, but the most affected skin region
      was the area around the cloaca. Behavior, condition, and lifespan of infected
      frogs do not seem to be distinct from that of healthy individuals. The mode of
      infection remains unknown, but we hypothesize that the infectious life stage
      reaches the dermis via the intraepidermal ducts of the skin glands. Molecular
      evidence places the new frog pathogen as a sister species of the human pathogen
      R. seeberi. 

PMID- 26203883
TI  - Consistent isotopic differences between Schistocephalus spp. parasites and their
      stickleback hosts.
AB  - Parasite-host systems show markedly variable patterns in isotopic fractionation:
      parasites can be either depleted or enriched in 15N and 13C as compared to their
      hosts. However, it remains unknown whether isotopic fractionation patterns are
      similar in comparable parasite-host systems from markedly different ecosystems.
      Results of this study show that large-sized Schistocephalus spp. endoparasites
      are consistently depleted in 15N (by on average -2.13 to -2.20 0/00) as compared
      to their nine-spined stickleback Pungitius pungitius and three-spined stickleback
      Gasterosteus aculeatus hosts. The differences between parasites and host for both
      delta15N and delta13C were consistent in both study systems despite marked
      biogeographical differences between the study localities. Although the stable
      isotope values in general were strongly correlated between the hosts and their
      parasites, Schistocephalus specimens occupying the same nine-spined stickleback
      host showed sometimes substantial individual variation in delta13C. This might be
      due to selective use of different carbon sources, or different metabolic or
      feeding rates. Further studies on selective feeding, physiology and metabolism of
      parasites are needed to better understand the role of parasites in the structure
      and functioning of aquatic food webs.

PMID- 26203884
TI  - Efficacy of commercially available products against Gyrodactylus turnbulli
      infections on guppies Poecilia reticulata.
AB  - The demand for ornamental fish has led to a steep rise in aquaculture for the
      hobbyist trade, promoting the emergence, persistence and spread of various
      infectious diseases. Complete control of disease outbreaks with antibiotics and
      chemical-based medicines is rare, but plant compounds may herald potential
      alternatives effective against a range of pathogens. Melafix(r) and Pimafix(r)
      are formulated with the essential oils cajuput (Melaleuca cajuputi) and West
      Indian bay (Pimenta racemosa) and are marketed against bacterial and fungal
      infections, respectively. Previous experiments showed high efficacy of emulsified
      cajuput oil against gyrodactylids; the current study tested Melafix(r) and
      Pimafix(r) and their individual compounds against Gyrodactylus turnbulli
      infecting the guppies Poecilia reticulata. In particular, a combination treatment
      of Melafix(r) and Pimafix(r) was highly effective at reducing in vitro survival
      of parasites from 15 to 2 h and eradicating 95% of gyrodactylids in vivo. The
      unexpected high efficacy of this combination treatment is likely explained by the
      high content of terpenes and phenol propanoids in the cajuput and West Indian bay
      oils, as well as the anti-helminthic properties of the emulsifier Crovol PK 70.
      Hence, Melafix(r) and Pimafix(r) effectively reduce gyrodactylid burdens on fish,
      increasing the chances of efficient disease control in ornamental fish. 

PMID- 26203885
TI  - Comparison of quantitative PCR and ELISA for detection and quantification of
      Flavobacterium psychrophilum in salmonid broodstock.
AB  - A quantitative PCR (qPCR) assay was developed for Flavobacterium psychrophilum,
      the causative agent of bacterial coldwater disease. The assay was targeted to
      fp1493 as it encodes a putative outer membrane protein (FP1493) that is reactive
      to the monoclonal antibody (MAb FL43) used in a standardized F. psychrophilum
      capture enzyme-linked immunosorbent assay (ELISA). The qPCR was specific to F.
      psychrophilum and was able to detect between 8 and 809000 copies of fp1493. To
      determine if antigen level in the tissue was indicative of bacterial
      concentration, kidney samples from 108 steelhead Oncorhynchus mykiss and coho
      salmon O. kisutch female broodstock were screened by ELISA and qPCR. There was no
      correlation between ELISA optical density (OD) values and the number of F.
      psychrophilum cells g-1 of kidney tissue as estimated by qPCR (rS = 0.42; p >
      0.05). The median number of F. psychrophilum cells in steelhead samples was 6.11
      * 103 cells g-1 of tissue. For coho salmon samples, the median number of cells
      was 3.95 * 103 cells g-1 of tissue. Agreement between the 2 assays was less than
      50%. As fp1493 is a single-copy gene and differential expression of FP1493 has
      been reported, we hypothesize that the discrepancy between the 2 assays is due to
      increased expression of FP1493 in the in vivo environment. Therefore, ELISA OD
      values most likely provide an indication of differential protein expression,
      while the qPCR assay estimates bacterial load in tissue.

PMID- 26203886
TI  - Skin lesion-associated pathogens from Octopus vulgaris: first detection of
      Photobacterium swingsii, Lactococcus garvieae and betanodavirus.
AB  - The common octopus Octopus vulgaris Cuvier, 1798 is extremely important in
      fisheries and is a useful protein source in most Mediterranean countries. Here we
      investigated pathogens associated with skin lesions in 9 naturally deceased
      specimens that included both cultured and wild common octopus. Within 30 min
      after death, each octopus was stored at 4 degrees C and microbiologically
      examined within 24 h. Bacterial colonies, cultured from swabs taken from the
      lesions, were examined using taxonomical and biochemical analyses. Vibrio
      alginolyticus and V. parahaemolyticus were only isolated from cultured animals. A
      conventional PCR targeting the 16S ribosomal RNA (rRNA) gene and sequencing were
      performed on 2 bacterial isolates that remained unidentified after taxonomical
      and biochemical analysis. The sequence results indicated that the bacteria had a
      99% identity with Lactococcus garvieae and Photobacterium swingsii. L. garvieae
      was confirmed using a specific PCR based on the 16S-23S rRNA internal transcribed
      spacer region, while P. swingsii was confirmed by phylogenetic analyses. Although
      all animals examined were found to be infected by the protozoan species Aggregata
      octopiana localised in the intestines, it was also present in skin lesions of 2
      of the animals. Betanodavirus was detected in both cultured and wild individuals
      by cell culture, PCR and electron microscopy. These findings are the first report
      of L. garvieae and betanodavirus from skin lesions of common octopus and the
      first identification of P. swingsii both in octopus skin lesions and in marine
      invertebrates in Italy. 

PMID- 26203887
TI  - Emilia sonchifolia extract activity against white spot syndrome virus and yellow
      head virus in shrimp cell cultures.
AB  - Emilia sonchifolia (L.) DC is a plant used in traditional medicine to treat
      several viral and bacterial diseases. The antiviral activities of selected
      Sephadex LH-20 column fractions and HPLC subfractions of an acetone extract of E.
      sonchifolia leaves were determined in shrimp Penaeus merguiensis primary lymphoid
      cells infected with either white spot syndrome virus (WSSV) or yellow head virus
      (YHV). WSSV and YHV replication was quantified using quantitative real-time PCR
      tests targeted to the VP19 and ORF1b gene transcripts, respectively. In lymphoid
      organ cells exposed to 100 ug ml-1 of either the Sephadex fraction F14 or the
      HPLC F14 subfraction SF4, both fractions caused reduced replication, but YHV
      replication was reduced only by SF4. In the asthiazolyl blue mitochondrial enzyme
      activity assays to assess extract cytotoxicity, >60% of primary lymphoid organ
      cells remained viable following exposure to 100 ug ml-1 of either F14 or SF4. GC
      MS analysis of the HPLC F14 subfraction SF4 showed that it contained 2,4-di-tert
      butylphenol. This study is the first to show that E. sonchifolia leaf extracts
      might be useful as bioactive agents to protect shrimp against viruses such as
      WSSV and YHV.

PMID- 26203888
TI  - Coral health on reefs near mining sites in New Caledonia.
AB  - Coral health data are poorly documented in New Caledonia, particularly from reefs
      chronically subject to anthropogenic and natural runoff. We investigated patterns
      of coral disease and non-disease conditions on reefs situated downstream of
      mining sites off the coast of New Caledonia. Surveys were conducted in March 2013
      at 2 locations along the west coast and 2 locations along the east coast of the
      main island. Only 2 coral diseases were detected: growth anomalies and white
      syndrome. The most prevalent signs of compromised health at each location were
      sediment damage and algal overgrowth. These results support earlier findings that
      sedimentation and turbidity are major threats to in-shore reefs in New Caledonia.
      The Poritidae-dominated west coast locations were more subject to sediment
      damage, algal overgrowth and growth anomalies compared to the Acroporidae
      dominated east coast locations. If growth form and resistance of coral hosts
      influence these results, differences in environmental conditions including hydro
      dynamism between locations may also contribute to these outputs. Our results
      highlight the importance of combining coral health surveys with measurements of
      coral cover when assessing the health status of a reef, as reefs with high coral
      cover may have a high prevalence of corals demonstrating signs of compromised
      health.

PMID- 26203889
TI  - Fabrication of Ultrasensitive Field-Effect Transistor DNA Biosensors by a
      Directional Transfer Technique Based on CVD-Grown Graphene.
AB  - Most graphene field-effect transistor (G-FET) biosensors are fabricated through a
      routine process, in which graphene is transferred onto a Si/SiO2 substrate and
      then devices are subsequently produced by micromanufacture processes. However,
      such a fabrication approach can introduce contamination onto the graphene surface
      during the lithographic process, resulting in interference for the subsequent
      biosensing. In this work, we have developed a novel directional transfer
      technique to fabricate G-FET biosensors based on chemical-vapor-deposition- (CVD
      ) grown single-layer graphene (SLG) and applied this biosensor for the sensitive
      detection of DNA. A FET device with six individual array sensors was first
      fabricated, and SLG obtained by the CVD-growth method was transferred onto the
      sensor surface in a directional manner. Afterward, peptide nucleic acid (PNA) was
      covalently immobilized on the graphene surface, and DNA detection was realized by
      applying specific target DNA to the PNA-functionalized G-FET biosensor. The
      developed G-FET biosensor was able to detect target DNA at concentrations as low
      as 10 fM, which is 1 order of magnitude lower than those reported in a previous
      work. In addition, the biosensor was capable of distinguishing the complementary
      DNA from one-base-mismatched DNA and noncomplementary DNA. The directional
      transfer technique for the fabrication of G-FET biosensors is simple, and the as
      constructed G-FET DNA biosensor shows ultrasensitivity and high specificity,
      indicating its potential application in disease diagnostics as a point-of-care
      tool. 

PMID- 26203890
TI  - Exchange and Inelastic OH(+) + H Collisions on the Doublet and Quartet Electronic
      States.
AB  - The exchange and inelastic state-to-state cross sections for the OH(+) + H
      collisions are computed from wave packet calculations using the doublet and
      quartet ground electronic potential energy surface (PES) correlating to the open
      shell reactants, for collision energies in the range of 1 meV to 0.7 eV. The
      doublet PES presents a deep insertion well, of ~6 eV, but the exchange reaction
      has a rather low probability, showing that the mechanism is not statistical. This
      well is also responsible of a rather high rotational energy transfer, which makes
      the rigid-rotor approach overestimate the cross section for low Deltaj
      transitions and for high collisonal energies. The quartet PES, with a much
      shallower well, also presents a low exchange reaction cross section, but the
      inelastic state-to-state cross sections are very well reproduced by rigid-rotor
      calculations. When the electronic partition is used to obtain the total state-to
      state cross section, the contribution of the doublet state becomes small, and the
      resulting total cross sections become close to those obtained for the quartet
      state. Thus, the total (quartet and doublet) cross sections for this open shell
      system can be reproduced rather satisfactorily by those obtained with the rigid
      rotor approximation on the quartet state. Finally, we compare the new OH(+)-H
      cross sections with OH(+)-He ones recently computed. We found significant
      differences, especially for transitions with large Deltaj showing that specific
      OH(+)-H calculations had to be performed to accurately analyze the OH(+) emission
      from interstellar molecular clouds. 

PMID- 26203891
TI  - Formation of Ground State Triplet Diradicals from Annulated Rosarin Derivatives
      by Triprotonation.
AB  - Annulated rosarins, beta,beta'-bridged hexaphyrin(1.0.1.0.1.0) derivatives 1-3,
      are formally 24 pi-electron antiaromatic species. At low temperature, rosarins 2
      and 3 are readily triprotonated in the presence of trifluoroacetic acid in
      dichloromethane to produce ground state triplet diradicals, as inferred from
      electron paramagnetic resonance (EPR) spectral studies. From an analysis of the
      fine structure in the EPR spectrum of triprotonated rosarin H33(3+), a distance
      of 3.6 A between the two unpaired electrons was estimated. The temperature
      dependence of the singlet-triplet equilibrium was determined by means of an EPR
      titration. Support for these experimental findings came from calculations carried
      out at the (U)B3LYP/6-31G* level, which served to predict a very low-lying
      triplet state for the triprotonated form of a simplified model system 1.

PMID- 26203892
TI  - Review of PAH contamination in food products and their health hazards.
AB  - Public concern over the deleterious effects of polycyclic aromatic hydrocarbons
      (PAHs) has grown rapidly due to recognition of their toxicity, carcinogenicity,
      and teratogenicity. The aim of this review is to describe the status of PAH
      pollution among different food types, the route of dietary intake, measures for
      its reduction, and legislative approaches to control PAH. To this end, a
      comprehensive review is outlined to evaluate the status of PAH contamination in
      many important food categories along with dietary recommendations. Our discussion
      is also extended to describe preventive measures to reduce PAH in food products
      to help reduce the risks associated with human intake. 

PMID- 26203893
TI  - Tuning Morphology of Nanostructured ZIF-8 on Silica Microspheres and Applications
      in Liquid Chromatography and Dye Degradation.
AB  - Zeolitic imidazolate framework-8 (ZIF-8) is one type of metal-organic framework
      (MOF) with excellent thermal and solvent stability and has been used extensively
      in separation, catalysis, and gas storage. Supported ZIF-8 structures can offer
      additional advantages beyond the MOF-only materials. Here, spheres-on-spheres
      (SOS) silica microspheres are used as support for the nucleation and growth of
      ZIF-8 nanocrystals. The surface functionalities (-SH, -COOH, and -NH2) of silica
      and reaction conditions are investigated for their effects on the ZIF-8
      morphology. The use of SOS microspheres results in the formation of highly
      crystalline ZIF-8 nanostructured shell with varied sizes and shapes, ranging from
      spherical to cubic and to needle crystals. The SOS@ZIF-8 microspheres are packed
      into a column and utilized for separation of aromatic molecules on the basis of
      pi-pi interaction in high-performance liquid chromatography (HPLC). Furthermore,
      by thermal treatment in air, ZIF-8 nanocrystals can be transformed into ZnO
      coating on SOS silica microspheres. The SOS@ZnO microspheres show excellent
      photocatalytic activity, as measured by degradation of methyl orange in water,
      when compared to ZnO nanoparticles. This study has demonstrated the facile way of
      using SOS microspheres to prepare core-shell microspheres and their applications.

PMID- 26203895
TI  - Accurate quantum chemical modelling of the separation of Eu(3+) from
      Am(3+)/Cm(3+) by liquid-liquid extraction with Cyanex272.
AB  - The experimentally observed extraction complexes of trivalent lanthanide Eu(3+)
      and actinide Am(3+)/Cm(3+) cations with Cyanex272 [bis(2,4,4-trimethylpentyl)
      phosphinic acid, denoted as HC272] and Cyanex301 [bis(2,4,4-trimethylpentyl)
      dithiophosphinic acid, denoted as HC301] have been studied by using relativistic
      energy-consistent 4f- and 5f-in-core pseudopotentials for trivalent f elements,
      combined with density functional theory and a continuum solvation model. It has
      been found that, as a result of hydrogen bonding, HC272 exists primarily as a
      self-associated species, whereas HC301 is preferably a monomer. The calculations
      show that in case of all three M(3+) (M = Eu, Am, Cm) ions for HC272 the
      extraction complexes M[H(C272)2]3 are formed prior to M(C272)3, whereas for HC301
      the extraction complexes M(C301)3 have priority over M[H(C301)2]3. The calculated
      M-O and M-S bond lengths and the M-P distances of these preferred extraction
      complexes agree very well with the available experimental data. The obtained
      changes of the Gibbs free energies in the liquid-liquid extraction reactions (1):
      Maqu(3+) + 3(HC272)2,org-> M[H(C272)2]3,org + 3Haqu(+) and (2): Maqu(3+) +
      3HC301org-> M(C301)3,org + 3Haqu(+) agree with the experimentally observed
      thermodynamical priorities of HC272 and HC301, i.e., HC272 prefers Eu(3+) over
      Am(3+)/Cm(3+) and HC301 prefers Am(3+)/Cm(3+) over Eu(3+). The obtained changes
      of the Gibbs free energies in reaction (2) (Eu, 68.1 kJ mol(-1); Am, 46.5 kJ mol(
      1)) agree quite well with the experimental findings (Eu, 63.3 kJ mol(-1); Am,
      44.1 kJ mol(-1)). 

PMID- 26203894
TI  - TEMPO-Promoted Domino Heck-Suzuki Arylation: Diastereoselective Cis-Diarylation
      of Glycals and Pseudoglycals.
AB  - A palladium-catalyzed regio- and diastereoselective diarylation of glycals and
      pseudoglycals, which is a kind of Heck-Suzuki arylation, is described. A wide
      range of arylboronic acids reacted under these conditions smoothly. Selectivity
      was C1-C2(alpha,alpha) in the case of glycals but C2-C3(beta,beta) for
      pseudoglycals. Quantum chemical analysis has been carried out to establish the
      reaction mechanism, which may involve Pd(II)/Pd(O). TEMPO plays a key role in the
      formation of diaryl glycoside due to its radical nature. 

PMID- 26203896
TI  - Aromatic amine N-oxide organometallic compounds: searching for prospective agents
      against infectious diseases.
AB  - In search of prospective agents against infectious diseases, 1,1'
      bis(diphenylphosphino)ferrocene pyridine-2-thiolato-1-oxide M(ii)
      hexafluorophosphate compounds [M(mpo)(dppf)](PF6), where M = palladium or
      platinum, were synthesized and fully characterized in the solid state and in
      solution using experimental and DFT computational techniques. The compounds are
      isomorphous and the M(ii) transition metal ions are in a nearly planar
      trapezoidal cis-coordination bound to the pyridine-2-thiolato-1-oxide (mpo) and
      to the 1,1'-bis(diphenylphosphino)ferrocene molecules, both acting as bidentate
      ligands. Both compounds showed high cytotoxic activity on Trypanosoma cruzi and
      Mycobacterium tuberculosis (MTB) and acceptable selectivities towards MTB, but
      good to excellent selectivity index values as anti-T. cruzi compounds. The
      inclusion of the ferrocene moiety (dppf ligand) improved the selectivity towards
      the parasite when compared to the previously reported [M(mpo)2] complexes.
      Related to the probable mechanism of action of the complexes, molecular docking
      studies on modelled T. cruzi NADH-fumarate reductase (TcFR) predicted that both
      be very good inhibitors of the enzyme. The effect of the compounds on the enzyme
      activity was experimentally confirmed using T. cruzi protein extracts. According
      to all obtained results, both [M(mpo)(dppf)](PF6) compounds could be considered
      prospective anti-trypanosomal agents that deserve further research. 

PMID- 26203897
TI  - Hybrid van der Waals heterostructures of zero-dimensional and two-dimensional
      materials.
AB  - van der Waals heterostructures meet other low-dimensional materials. Stacking of
      about 1 nm thick nanosheets with out-of-plane anchor groups functionalized with
      fullerenes integrates this zero-dimensional material into layered
      heterostructures with a well-defined chemical composition and without degrading
      the mechanical properties. The developed modular and highly applicable approach
      enables the incorporation of other low-dimensional materials, e.g. nanoparticles
      or nanotubes, into heterostructures significantly extending the possible building
      blocks. 

PMID- 26203898
TI  - Comment on "Sensitive marker bands for the detection of spin states of heme in
      surface-enhanced resonance Raman scattering spectra of metmyoglobin" by Y.
      Kitahama, M. Egashira, T. Suzuki, I. Tanabe and Y. Ozaki.
AB  - We contrast recently reported surface-enhanced resonance Raman spectra (SERRS) of
      myoglobin on silver nanoparticles with established knowledge about this complex.
      We conclude that the detected bands are not related to the spin states of the
      protein cofactor, being rather originated by a heme coordination change induced
      by the metal surface. 

PMID- 26203899
TI  - Theoretical study of the pathway to heterogeneous nucleation of liquid copper on
      the groove substrate with different wedge angles.
AB  - Heterogeneous nucleation is of significance in controlling the crystal growth,
      but the key route is still limited. Simulations are performed to explore the
      microscopic details of how the wedge substrate spreads its structural information
      to a growing crystal and further affects the solidification process. The
      simulation results show that, owing to the induced effect from the substrate, the
      copper atoms become layered at the liquid-solid interface in a "V"-shaped pattern
      and tend to form a twin crystal. The structural information delivery of the
      substrate decays with the distance away from the substrate, and the final
      solidified structure would gradually recover its inherent structure.
      Interestingly, the wedge angle of 90 degrees  seems to be an exception at which
      the solidified structure exhibits a perfect crystal due to the nearly perfect
      match with the Cu atoms. Moreover, the cooling rate and the atomic structure of
      the substrate are also found to have striking correlations with the final
      structures. These research results are favorable for a better understanding of
      the inherent relation between the solidified structure and the substrate. 

PMID- 26203900
TI  - 2-Oxo promoted hydrophosphonylation & aerobic intramolecular nucleophilic
      displacement reaction.
AB  - Highly efficient catalyst free methods for the synthesis of alpha-hydroxy-beta
      oxophosphonates and alpha-oxoesters have been described. The existence of a 2-oxo
      group in alpha-oxoaldehydes is a key factor in promoting the reaction of the
      tervalent phosphite form towards 2-oxoaldehydes in the synthesis of alpha-hydroxy
      beta-oxophosphonates. The in situ activated alpha-C-H atom of alpha-hydroxy-beta
      oxophosphonates sustains aerobic intramolecular nucleophilic displacement in a
      curious way to produce alpha-oxoester. 

PMID- 26203901
TI  - Phase-Dependent Enhancement of the Green-Emitting Upconversion Fluorescence in
      LaVO4:Yb(3+), Er(3+).
AB  - The phase-dependent upconversion luminescence properties of LaVO4:Er(3+) were
      studied to provide new insights into the design of new upconversion materials
      with high efficiency. Er(3+)-, Yb(3+)/Er(3+)-doped t-LaVO4 microcrystals were
      successfully synthesized by the disodium ethylenediaminetetraacetic acid
      (Na2EDTA)-assisted hydrothermal method. X-ray diffraction (XRD), inductively
      coupled plasma optical emission spectrometer (ICP-OES), Fourier transform
      infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), Raman spectroscopy, luminescence spectroscopy, and
      thermogravimetric analysis (TGA) were used to characterize the samples. The
      results indicated that t-LaVO4 presents sheaf-like morphology, and the possible
      formation mechanism for these sheaves was proposed on the basis of time-dependent
      experiments. Furthermore, the phase-dependence (i.e., monoclinic- and tetragonal
      type) upconversion luminescence properties were systematically studied, and the
      upconversion mechanisms were proposed according to spectral, pump power, and the
      concentration of Yb(3+) dependence analyses. It is worthwhile pointing out that
      the Er(3+)-doped t-LaVO4 exhibits a brighter green emission, which is
      approximately 10 times that of m-LaVO4:Er(3+) using a continuous 980 nm laser
      diode as the excitation source. This remarkable improvement was rationally
      analyzed on the basis of the composition, crystal structures, Raman spectra,
      morphology, and size. The comparative experiments suggest that the local
      structure of Er(3+) was considered as an important reason for the higher
      fluorescence intensity of t-LaVO4:Er(3+), which was also confirmed by the results
      of density functional theory (DFT) calculations. 

PMID- 26203902
TI  - The impact of the thermal conductivity of a dielectric layer on the self-heating
      effect of a graphene transistor.
AB  - The self-heating effect of a graphene transistor on the transport properties was
      studied. Different dielectric layers, SiO2 and AlN, which have different thermal
      conductivities, were used to tune the thermal dissipation of the graphene
      transistor. An obvious change in channel resistance and a shift of charge
      neutrality point were observed during the operation of the transistor with SiO2,
      while the change is slight when AlN is the dielectric layer. This observation is
      considered to be related to the temperature determined desorption rate of p-type
      dopants in graphene. 

PMID- 26203903
TI  - Noise-Driven Phenotypic Heterogeneity with Finite Correlation Time in Clonal
      Populations.
AB  - There has been increasing awareness in the wider biological community of the role
      of clonal phenotypic heterogeneity in playing key roles in phenomena such as
      cellular bet-hedging and decision making, as in the case of the phage-lambda
      lysis/lysogeny and B. Subtilis competence/vegetative pathways. Here, we report on
      the effect of stochasticity in growth rate, cellular memory/intermittency, and
      its relation to phenotypic heterogeneity. We first present a linear stochastic
      differential model with finite auto-correlation time, where a randomly
      fluctuating growth rate with a negative average is shown to result in exponential
      growth for sufficiently large fluctuations in growth rate. We then present a non
      linear stochastic self-regulation model where the loss of coherent self
      regulation and an increase in noise can induce a shift from bounded to unbounded
      growth. An important consequence of these models is that while the average change
      in phenotype may not differ for various parameter sets, the variance of the
      resulting distributions may considerably change. This demonstrates the necessity
      of understanding the influence of variance and heterogeneity within seemingly
      identical clonal populations, while providing a mechanism for varying functional
      consequences of such heterogeneity. Our results highlight the importance of a
      paradigm shift from a deterministic to a probabilistic view of clonality in
      understanding selection as an optimization problem on noise-driven processes,
      resulting in a wide range of biological implications, from robustness to
      environmental stress to the development of drug resistance. 

PMID- 26203904
TI  - Low Dietary Diversity and Intake of Animal Source Foods among School Aged
      Children in Libo Kemkem and Fogera Districts, Ethiopia.
AB  - BACKGROUND: A low dietary diversity score (DDS) and low consumption of food from
      animal sources (ASF) are among the factors related to malnutrition in school-aged
      children living in Libo Kemkem and Fogera (Ethiopia). OBJECTIVES: This study
      aimed to identify associated determinants for low dietary diversity and lack of
      consumption of ASF. METHODS: In 2009, a cross-sectional survey was carried out in
      May, at the end of the lean season. Socio-demographic characteristics and diet
      habits were collected from 886 school-aged children. Additionally, 516 children
      from rural sites were followed up in the post-harvest season, in December of the
      same year. Bivariate and multivariable statistical methods were employed to
      assess low DDS and ASF intake and their association with different factors.
      RESULTS: Up to 80% and 60% of school-aged children living in rural and urban
      sites, respectively, ate <= 3 food groups the day before the survey. The
      percentage of children consuming ASF was significantly higher in urban settings
      (64% vs 18%). In the rural areas, if the head of the household was male (OR:
      1.91; 95%CI: 1.00-3.65) and older than 40 years (OR: 1.56; 95%CI: 1.02-2.38) the
      child had a lower DDS in the lean season, while differences by socioeconomic
      indexes were observed in the post-harvest season. Males took more ASF than
      females in rural settings (OR: 1.73; 95%CI: 1.14-2.62) and differences by
      socioeconomic indexes were observed in both settings in the lean season, though
      not in post-harvest survey. CONCLUSIONS: The findings of this study revealed that
      the diet among school-aged children in Libo Kemkem and Fogera districts lacked
      diversity, and that the intake of foods from animal sources was low, especially
      among rural girls. To effectively tackle malnutrition, dietary diversification
      strategies oriented to the local needs are recommended.

PMID- 26203905
TI  - Cross Kingdom Activators of Five Classes of Bacterial Effectors.

PMID- 26203906
TI  - Norepinephrine-Induced Adrenergic Activation Strikingly Increased the Atrial
      Fibrillation Duration through beta1- and alpha1-Adrenergic Receptor-Mediated
      Signaling in Mice.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmias among old
      people. It causes serious long-term health problems affecting the quality of
      life. It has been suggested that the autonomic nervous system is involved in the
      onset and maintenance of AF in human. However, investigation of its pathogenesis
      and potential treatment has been hampered by the lack of suitable AF models in
      experimental animals. OBJECTIVES: Our aim was to establish a long-lasting AF
      model in mice. We also investigated the role of adrenergic receptor (AR)
      subtypes, which may be involved in the onset and duration of AF. METHODS AND
      RESULTS: Trans-esophageal atrial burst pacing in mice could induce AF, as
      previously shown, but with only a short duration (29.0 +/- 8.1 sec). We found
      that adrenergic activation by intraperitoneal norepinephrine (NE) injection
      strikingly increased the AF duration. It increased the duration to more than 10
      minutes, i.e., by more than 20-fold (656.2 +/- 104.8 sec; P<0.001). In this
      model, a prior injection of a specific beta1-AR blocker metoprolol and an alpha1
      AR blocker prazosin both significantly attenuated NE-induced elongation of AF. To
      further explore the mechanisms underlying these receptors' effects on AF, we
      assessed the SR Ca(2+) leak, a major trigger of AF, and consequent spontaneous SR
      Ca(2+) release (SCR) in atrial myocytes. Consistent with the results of our in
      vivo experiments, both metoprolol and prazosin significantly inhibited the NE
      induced SR Ca(2+) leak and SCR. These findings suggest that both beta1-AR and
      alpha1-AR may play important roles in the development of AF. CONCLUSIONS: We have
      established a long-lasting AF model in mice induced by adrenergic activation,
      which will be valuable in future AF study using experimental animals, such as
      transgenic mice. We also revealed the important role of beta1- and alpha1-AR
      mediated signaling in the development of AF through in-vivo and in-vitro
      experiments.

PMID- 26203907
TI  - Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative
      Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells.
AB  - For multiple sclerosis, genome wide association studies and follow up studies
      have identified susceptibility single nucleotide polymorphisms located in or near
      CLEC16A at chromosome 16p13.13, encompassing among others CIITA, DEXI and SOCS1
      in addition to CLEC16A. These genetic variants are located in intronic or
      intergenic regions and display strong linkage disequilibrium with each other,
      complicating the understanding of their functional contribution and the
      identification of the direct causal variant(s). Previous studies have shown that
      multiple sclerosis-associated risk variants in CLEC16A act as expression
      quantitative trait loci for CLEC16A itself in human pancreatic beta-cells, for
      DEXI and SOCS1 in thymic tissue samples, and for DEXI in monocytes and
      lymphoblastoid cell lines. Since T cells are major players in multiple sclerosis
      pathogenesis, we have performed expression analyses of the CIITA-DEXI-CLEC16A
      SOCS1 gene cluster in CD4+ and CD8+ T cells isolated from multiple sclerosis
      patients and healthy controls. We observed a higher expression of SOCS1 and
      CLEC16A in CD4+ T cells in samples homozygous for the risk allele of CLEC16A
      rs12927355. Pair-wise linear regression analysis revealed high correlation in
      gene expression in peripheral T cells of CIITA, DEXI, CLEC16A and SOCS1. Our data
      imply a possible regulatory role for the multiple sclerosis-associated rs12927355
      in CLEC16A. 

PMID- 26203908
TI  - Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation.
AB  - Four related cows showed hairless streaks on various parts of the body with no
      correlation to the pigmentation pattern. The stripes occurred in a consistent
      pattern resembling the lines of Blaschko. The non-syndromic hairlessness
      phenotype observed occurred across three generations of a single family and was
      compatible with an X-linked mode of inheritance. Linkage analysis and subsequent
      whole genome sequencing of one affected female identified two perfectly
      associated non-synonymous sequence variants in the critical interval on bovine
      chromosome X. Both variants occurred in complete linkage disequilibrium and were
      absent in more than 3900 controls. An ERCC6L missense mutation was predicted to
      cause an amino acid substitution of a non-conserved residue. Analysis in mice
      showed no specific Ercc6l expression pattern related to hair follicle development
      and therefore ERCC6L was not considered as causative gene. A point mutation at
      the 5'-splice junction of exon 5 of the TSR2, 20S rRNA accumulation, homolog (S.
      cerevisiae), gene led to the production of two mutant transcripts, both of which
      contain a frameshift and generate a premature stop codon predicted to truncate
      approximately 25% of the protein. Interestingly, in addition to the presence of
      both physiological TSR2 transcripts, the two mutant transcripts were
      predominantly detected in the hairless skin of the affected cows.
      Immunohistochemistry, using an antibody against the N-terminal part of the bovine
      protein demonstrated the specific expression of the TSR2 protein in the skin and
      the hair of the affected and the control cows as well as in bovine fetal skin and
      hair. The RNA hybridization in situ showed that Tsr2 was expressed in pre- and
      post-natal phases of hair follicle development in mice. Mammalian TSR2 proteins
      are highly conserved and are known to be broadly expressed, but their precise in
      vivo functions are poorly understood. Thus, by dissecting a naturally occurring
      mutation in a domestic animal species, we identified TSR2 as a regulator of hair
      follicle development. 

PMID- 26203909
TI  - Physical Activities Monitoring Using Wearable Acceleration Sensors Attached to
      the Body.
AB  - Monitoring physical activities by using wireless sensors is helpful for
      identifying postural orientation and movements in the real-life environment. A
      simple and robust method based on time domain features to identify the physical
      activities is proposed in this paper; it uses sensors placed on the subjects'
      wrist, chest and ankle. A feature set based on time domain characteristics of the
      acceleration signal recorded by acceleration sensors is proposed for the
      classification of twelve physical activities. Nine subjects performed twelve
      different types of physical activities, including sitting, standing, walking,
      running, cycling, Nordic walking, ascending stairs, descending stairs, vacuum
      cleaning, ironing clothes and jumping rope, and lying down (resting state). Their
      ages were 27.2 +/- 3.3 years and their body mass index (BMI) is 25.11 +/- 2.6
      Kg/m2. Classification results demonstrated a high validity showing precision (a
      positive predictive value) and recall (sensitivity) of more than 95% for all
      physical activities. The overall classification accuracy for a combined feature
      set of three sensors is 98%. The proposed framework can be used to monitor the
      physical activities of a subject that can be very useful for the health
      professional to assess the physical activity of healthy individuals as well as
      patients. 

PMID- 26203910
TI  - Atmospheric-Pressure Cold Plasma Induces Transcriptional Changes in Ex Vivo Human
      Corneas.
AB  - BACKGROUND: Atmospheric pressure cold plasma (APCP) might be considered a novel
      tool for tissue disinfection in medicine since the active chemical species
      produced by low plasma doses, generated by ionizing helium gas in air, induces
      reactive oxygen species (ROS) that kill microorganisms without substantially
      affecting human cells. OBJECTIVES: In this study, we evaluated morphological and
      functional changes in human corneas exposed for 2 minutes (min) to APCP and
      tested if the antioxidant n-acetyl l-cysteine (NAC) was able to inhibit or
      prevent damage and cell death. RESULTS: Immunohistochemistry and western blotting
      analyses of corneal tissues collected at 6 hours (h) post-APCP treatment
      demonstrated no morphological tissue changes, but a transient increased
      expression of OGG1 glycosylase that returned to control levels in 24 h.
      Transcriptome sequencing and quantitative real time PCR performed on different
      corneas revealed in the treated corneas many differentially expressed genes:
      namely, 256 and 304 genes showing expression changes greater than +/- 2 folds in
      the absence and presence of NAC, respectively. At 6 h post-treatment, the most
      over-expressed gene categories suggested an active or enhanced cell functioning,
      with only a minority of genes specifically concerning oxidative DNA damage and
      repair showing slight over-expression values (<2 folds). Moreover, time-related
      expression analysis of eight genes up-regulated in the APCP-treated corneas
      overall demonstrated the return to control expression levels after 24 h.
      CONCLUSIONS: These findings of transient oxidative stress accompanied by wide
      range transcriptome adjustments support the further development of APCP as an
      ocular disinfectant.

PMID- 26203911
TI  - Structural Brain Changes in Patients With COPD.
AB  - BACKGROUND: Patients with COPD suffer from chronic dyspnea, which is commonly
      perceived as highly aversive and threatening. Moreover, COPD is often accompanied
      by disease-specific fears and avoidance of physical activity. However, little is
      known about structural brain changes in patients with COPD and respective
      relations with disease duration and disease-specific fears. METHODS: This study
      investigated structural brain changes in patients with COPD and their relation
      with disease duration, fear of dyspnea, and fear of physical activity. We used
      voxel-based morphometric analysis of MRI images to measure differences in
      generalized cortical degeneration and regional gray matter between 30 patients
      with moderate to severe COPD and 30 matched healthy control subjects. Disease
      specific fears were assessed by the COPD anxiety questionnaire. RESULTS: Patients
      with COPD showed no generalized cortical degeneration, but decreased gray matter
      in posterior cingulate cortex (whole-brain analysis) as well as in anterior and
      midcingulate cortex, hippocampus, and amygdala (regions-of-interest analyses).
      Patients' reductions in gray matter in anterior cingulate cortex were negatively
      correlated with disease duration, fear of dyspnea, and fear of physical activity.
      Mediation analysis revealed that the relation between disease duration and
      reduced gray matter of the anterior cingulate was mediated by fear of physical
      activity. CONCLUSIONS: Patients with COPD demonstrated gray matter decreases in
      brain areas relevant for the processing of dyspnea, fear, and antinociception.
      These structural brain changes were partly related to longer disease duration and
      greater disease-specific fears, which might contribute to a less favorable course
      of the disease.

PMID- 26203913
TI  - Distinct pathways in the pathogenesis of sebaceous carcinomas implicated by
      differentially expressed microRNAs.
AB  - IMPORTANCE: The molecular-genetic alterations contributing to the pathogenesis of
      sebaceous carcinoma and sebaceous adenoma remain poorly understood. Given that
      sebaceous carcinoma is associated with substantial morbidity and mortality, there
      is a critical need to delineate the pathways driving sebaceous carcinoma and
      candidate molecules for targeted therapy. OBJECTIVE: To describe differentially
      expressed microRNAs (miRNAs) in a series of periocular sebaceous carcinomas
      compared with sebaceous adenomas in order to identify pathways driving the
      pathogenesis of sebaceous carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Thirty
      sebaceous carcinomas and 23 sebaceous adenomas (including 11 that were confirmed
      to be related to Muir-Torre syndrome and 6 that were confirmed to be sporadic)
      were obtained from archives (from 48 patients) of 2 institutions (University of
      Texas MD Anderson Cancer Center, Houston, and Siriraj Hospital, Mahidol
      University, Bangkok, Thailand) and profiled. MAIN OUTCOMES AND MEASURES:
      Expression of miRNAs was determined using total RNA from formalin-fixed, paraffin
      embedded tissue and real-time reverse transcription-polymerase chain reaction
      performed in a microfluidics card containing 378 unique miRNAs. Fold change was
      determined using the DeltaDeltaCt method (reference probe, RNU48). Median
      centering was used to normalize the data. Two-sample t tests were used to
      identify differentially expressed miRNAs. The false discovery rate was assessed
      by beta-uniform mixture analysis of P values from the t statistics. Significance
      was defined by this estimated false discovery rate. RESULTS: Serial testing and
      validation confirmed overexpression of 2 miRNAs previously reported to be
      oncogenic, miR-486-5p (4.4-fold; P = 2.4 * 10-8) and miR-184 (3.5-fold; P = 1.7 *
      10-6), in sebaceous carcinoma compared with sebaceous adenoma and downregulation
      of 2 miRNAs previously reported to have tumor-suppressive properties, miR-211 (
      5.8-fold; P = 2.3 * 10-9) and miR-518d (-4.5-fold; 6.7 * 10-5), in sebaceous
      carcinoma compared with sebaceous adenoma. CONCLUSIONS AND RELEVANCE: Sebaceous
      carcinoma exhibits an miRNA expression profile distinct from that of sebaceous
      adenoma, implicating dysregulation of NF-kappaB and PTEN (targets of miR-486-5p)
      and TGF-beta signaling (target of miR-211) in the pathogenesis of sebaceous
      carcinoma. The identification of miRNAs whose expression is altered in sebaceous
      carcinoma compared with sebaceous adenoma provides a novel entry point for a more
      comprehensive understanding of the molecular-genetic alterations pivotal to the
      development of sebaceous carcinoma.

PMID- 26203912
TI  - Chemotherapy Use, Performance Status, and Quality of Life at the End of Life.
AB  - IMPORTANCE: Although many patients with end-stage cancer are offered chemotherapy
      to improve quality of life (QOL), the association between chemotherapy and QOL
      amid progressive metastatic disease has not been well-studied. American Society
      for Clinical Oncology guidelines recommend palliative chemotherapy only for solid
      tumor patients with good performance status. OBJECTIVE: To evaluate the
      association between chemotherapy use and QOL near death (QOD) as a function of
      patients' performance status. DESIGN, SETTING, AND PARTICIPANTS: A multi
      institutional, longitudinal cohort study of patients with end-stage cancer
      recruited between September 2002 and February 2008. Chemotherapy use (n = 158
      [50.6%]) and Eastern Cooperative Oncology Group (ECOG) performance status were
      assessed at baseline (median = 3.8 months before death) and patients with
      progressive metastatic cancer (N = 312) following at least 1 chemotherapy regimen
      were followed prospectively until death at 6 outpatient oncology clinics in the
      United States. MAIN OUTCOMES AND MEASURES: Patient QOD was determined using
      validated caregiver ratings of patients' physical and mental distress in their
      final week. RESULTS: Chemotherapy use was not associated with patient survival
      controlling for clinical setting and patients' performance status. Among patients
      with good (ECOG score = 1) baseline performance status, chemotherapy use compared
      with nonuse was associated with worse QOD (odds ratio [OR], 0.35; 95% CI, 0.17
      0.75; P = .01). Baseline chemotherapy use was not associated with QOD among
      patients with moderate (ECOG score = 2) baseline performance status (OR, 1.06;
      95% CI, 0.51-2.21; P = .87) or poor (ECOG score = 3) baseline performance status
      (OR, 1.34; 95% CI, 0.46-3.89; P = .59). CONCLUSIONS AND RELEVANCE: Although
      palliative chemotherapy is used to improve QOL for patients with end-stage
      cancer, its use did not improve QOD for patients with moderate or poor
      performance status and worsened QOD for patients with good performance status.
      The QOD in patients with end-stage cancer is not improved, and can be harmed, by
      chemotherapy use near death, even in patients with good performance status.

PMID- 26203914
TI  - The Metabolic Syndrome and the Membrane Content of Polyunsaturated Fatty Acids in
      Hypertensive Patients.
AB  - BACKGROUND: Polyunsaturated fatty acids (PUFA) have been reported to be
      beneficial on some components of the metabolic syndrome (MetS). We tested the
      hypothesis that in hypertensive patients, presence of MetS and its related
      components is associated with cell membrane content of PUFA, a measure that
      reflects the dietary intake of these fatty acids. METHODS: In 55 consecutive
      patients with primary hypertension referred to our university center, we measured
      anthropometric variables, 24-hour ambulatory blood pressure, general
      biochemistries including plasma lipids, and the fatty acid composition of red
      blood cell (RBC) membrane by gas chromatography. RESULTS: The prevalence of the
      MetS was 36.4% and in hypertensive patients with MetS, the RBC membrane content
      of total PUFA, PUFA of the n-6 family (n-6 PUFA), PUFA of the n-3 family (n-3
      PUFA), polyunsaturated to saturated fatty acid ratio (PUFA/SFA), and omega-3
      index was significantly lower than in patients without MetS. RBC membrane total
      PUFA, n-6 PUFA, n-3 PUFA, PUFA/SFA ratio, and omega-3 index were significantly
      and directly correlated with high-desity lipoprotein (HDL) cholesterol levels, a
      correlation that did not differ across tertiles of plasma apolipoprotein-A1. In
      multivariate linear regression analysis, HDL-cholesterol resulted to be directly
      and independently related to RBC membrane n-6 PUFA, PUFA/SFA ratio, and omega-3
      index. Conversely, total cholesterol to HDL-cholesterol ratio had inverse and
      independent relationship with n-6 PUFA, PUFA/SFA ratio, and omega-3 index.
      CONCLUSIONS: In patients with hypertension the MetS is associated with lower cell
      membrane content of PUFA that is explained by a direct and independent
      relationship of membrane PUFA with HDL-cholesterol. This observation suggests
      reduced dietary intake of PUFA in these patients that might contribute to their
      cardiovascular risk.

PMID- 26203915
TI  - Mitochondrial E3 Ubiquitin Protein Ligase 1 Mediates Cigarette Smoke-Induced
      Endothelial Cell Death and Dysfunction.
AB  - By virtue of the critical roles of Akt in vascular endothelial cell (EC) survival
      and function, cigarette smoke-induced Akt reduction may contribute to EC death
      and dysfunction in smokers' lungs. One of the negative Akt regulatory mechanisms
      is K48-linked Akt ubiquitination and subsequent proteasomal degradation. Here, we
      assessed the involvement of mitochondrial E3 ubiquitin protein ligase 1 (MUL1),
      recently revealed as a novel Akt ubiquitin E3 ligase, in cigarette smoke-induced
      Akt ubiquitination and its contribution to pulmonary EC death and dysfunction. In
      human lung microvascular ECs (HLMVECs), cigarette smoke extract (CSE) noticeably
      elevated MUL1 expression and K48-linked Akt ubiquitination, whereas Akt, p-Akt,
      eNOS, and p-eNOS levels were decreased. MUL1 knockdown suppressed CSE-induced Akt
      ubiquitination/degradation and cytoplasmic reductions of Akt and p-Akt.
      Furthermore, MUL1 knockdown attenuated reductions of eNOS and p-eNOS and
      alleviated EC survival, migration, and tube formation in the presence of CSE
      exposure. In addition, overexpression of K284R Akt, a mutant for a MUL1
      ubiquitination site, produced similar effects. In HLMVECs exposed to CSE, Akt
      MUL1 interaction was increased in coimmunoprecipitation and in situ proximity
      ligation assays. Similarly, the proximity ligation assay signals were elevated in
      rat lungs exposed to cigarette smoke for 3 months, during which Mul1 levels were
      noticeably increased. Finally, we found that CSE-mediated MUL1 induction in
      HLMVECs is mediated by retinoic acid receptor-related orphan receptor alpha.
      Taken together, these data suggest that cigarette smoke-induced MUL1 elevation
      mediates Akt ubiquitination/degradation, potentially leading to pulmonary EC
      death and functional impairment. 

PMID- 26203916
TI  - Novel Bedside Phonetic Evaluation to Identify Dysphagia and Aspiration Risk.
AB  - BACKGROUND: There is a need for improved clinical identification of hospitalized
      patients at risk of aspiration. We evaluated our novel phonetic test in a broad
      spectrum of patients at risk of aspiration in the ICU or intermediate care unit.
      METHODS: We prospectively enrolled 60 hospitalized patients with aspiration risk,
      between December 2009 and September 2011, who subsequently underwent audio
      recorded three-component phonetic bedside evaluation. The recordings were scored
      by two blinded speech-language pathologists. The institutional dysphagia
      admission screening test was performed by a bedside nurse. The primary outcomes,
      dysphagia and aspiration, were assessed by a videofluoroscopic swallowing study,
      fiber-optic endoscopic evaluation of swallowing, or both. We assessed the short-
      and long-term clinical outcomes (length of stay, subsequent aspiration pneumonia
      and respiratory failure, survival) and how these were associated with the
      phonetic and swallow assessments. RESULTS: Statistically significant linear
      associations with dysphagia were noted for all three individual phonetic
      components. Also, there were statistically significant linear associations with
      aspiration for diadochokinesis (P = .050) and consensus auditory-perceptual
      evaluation of voice (P = .025). Diadochokinesis alone predicted dysphagia (area
      under the curve [AUC], 0.74; P = .001) and aspiration (AUC, 0.67; P = .012). Its
      predictive ability improved when combined with normalized dysphagia admission
      screening test results (AUC, 0.79; P = .001). The short- and long-term clinical
      outcomes were adversely affected by the worse phonetic/swallowing scores,
      although they were not statistically different. CONCLUSIONS: Abnormal phonation
      among ICU and intermediate care unit patients is associated with dysphagia and
      aspiration. Future investigative efforts should uncover the most effective
      combination of evaluations for accurate bedside detection of dysphagia and
      aspiration risk in a broad spectrum of patients.

PMID- 26203917
TI  - Pediatric Critical Care Telemedicine Program: A Single Institution Review.
AB  - BACKGROUND: Rural and community emergency departments (EDs) often receive and
      treat critically ill children despite limited access to pediatric expertise.
      Increasingly, pediatric critical care programs at children's hospitals are using
      telemedicine to provide consultations to these EDs with the goal of increasing
      the quality of care. MATERIALS AND METHODS: We conducted a retrospective review
      of a pediatric critical care telemedicine program at a single university
      children's hospital. Between the years 2000 and 2014, we reviewed all
      telemedicine consultations provided to children in rural and community EDs,
      classified the visits using a comprehensive evidence-based set of chief
      complaints, and reported the consultations' impact on patient disposition. We
      also reviewed the total number of pediatric ED visits to calculate the relative
      frequency with which telemedicine consultations were provided. RESULTS: During
      the study period, there were 308 consultations provided to acutely ill and/or
      injured children for a variety of chief complaints, most commonly for respiratory
      illnesses, acute injury, and neurological conditions. Since inception, the number
      of consultations has been increasing, as has the number of participating EDs (n =
      18). Telemedicine consultations were conducted on 8.6% of seriously ill children,
      the majority of which resulted in admission to the receiving hospital (n = 150,
      49%), with a minority of patients requiring transport to the university
      children's hospital (n = 103, 33%). CONCLUSIONS: This single institutional,
      university children's hospital-based review demonstrates that a pediatric
      critical care telemedicine program used to provide consultations to seriously ill
      children in rural and community EDs is feasible, sustainable, and used relatively
      infrequently, most typically for the sickest pediatric patients.

PMID- 26203920
TI  - Thyroid autoantibodies and the effect on pregnancy outcomes.
AB  - Thyroid antibody positivity is relatively common in women. While many
      epidemiological studies have investigated the links between thyroid antibodies
      and pregnancy complications, evidence regarding the effect of Levothyroxine
      treatment of euthyroid pregnant women with autoimmune thyroid disease on
      pregnancy outcome is limited. The objective of this paper is to provide a review
      on the impact of treatment of euthyroid thyroid antibody-positive pregnant women
      on adverse pregnancy outcome. This systematic review was conducted with a
      prospective protocol. PubMed, Science direct, Google scholar, Embase and the
      Cochrane Library databases were searched through January 2014 to identify studies
      that met pre-stated inclusion criteria. The search was limited to English
      manuscripts. We found that there is inadequate data regarding both the adverse
      effect of thyroid antibody positivity in euthyroid women on pregnancy outcomes
      and the effects Levothyroxine on these women. It seems that the results of most
      studies indicate adverse effects of thyroid antibody positivity in euthyroid
      women on pregnancy outcomes. Further randomised clinical trials are needed to
      investigate the effects of treating pregnant euthyroid women with positive
      thyroid antibodies on the maternal and early/late neonatal outcomes.

PMID- 26203919
TI  - Angiogenic Potential and Secretome of Human Apical Papilla Mesenchymal Stem Cells
      in Various Stress Microenvironments.
AB  - Stem cells from the apical papilla (SCAP) of human adult teeth are considered an
      accessible source of cells with angiogenic properties. The aims of this study
      were to investigate the endothelial transdifferentiation of SCAP, the secretion
      of pro- and antiangiogenic factors from SCAP, and the paracrine effects of SCAP
      when exposed to environmental stress to stimulate tissue damage. SCAP were
      exposed to serum deprivation (SD), glucose deprivation (GD), and oxygen
      deprivation/hypoxia (OD) conditions, individually or in combination. Endothelial
      transdifferentiation was evaluated by in vitro capillary-like formation assays,
      real-time polymerase chain reaction, western blot, and flow cytometric analyses
      of angiogenesis-related markers; secretome by antibody arrays and enzyme-linked
      immunosorbent assays (ELISA); and paracrine impact on human umbilical vein
      endothelial cells (HUVECs) by in vitro transwell migration and capillary-like
      formation assays. The short-term exposure of SCAP to glucose/oxygen deprivation
      (GOD) in the presence, but mainly in deprivation, of serum (SGOD) elicited a
      proangiogenesis effect indicated by expression of angiogenesis-related genes
      involved in vascular endothelial growth factor (VEGF)/VEGFR and angiopoietins/Tie
      pathways. This effect was unachievable under SD in normoxia, suggesting that the
      critical microenvironmental condition inducing rapid endothelial shift of SCAP is
      the combination of SGOD. Interestingly, SCAP showed high adaptability to these
      adverse conditions, retaining cell viability and acquiring a capillary-forming
      phenotype. SCAP secreted higher numbers and amounts of pro- (angiogenin, IGFBP-3,
      VEGF) and lower amounts of antiangiogenic factors (serpin-E1, TIMP-1, TSP-1)
      under SGOD compared with SOD or SD alone. Finally, secretome obtained under SGOD
      was most effective in inducing migration and capillary-like formation by HUVECs.
      These data provide new evidence on the microenvironmental factors favoring
      endothelial transdifferentiation of SCAP, uncovering the molecular mechanisms
      regulating their fate. They also validate the angiogenic properties of their
      secretome giving insights into preconditioning strategies enhancing their
      therapeutic potential. 

PMID- 26203921
TI  - The Brain Functional State of Music Creation: an fMRI Study of Composers.
AB  - In this study, we used functional magnetic resonance imaging (fMRI) to explore
      the functional networks in professional composers during the creation of music.
      We compared the composing state and resting state imagery of 17 composers and
      found that the functional connectivity of primary networks in the bilateral
      occipital lobe and bilateral postcentral cortex decreased during the composing
      period. However, significantly stronger functional connectivity appeared between
      the anterior cingulate cortex (ACC), the right angular gyrus and the bilateral
      superior frontal gyrus during composition. These findings indicate that a
      specific brain state of musical creation is formed when professional composers
      are composing, in which the integration of the primary visual and motor areas is
      not necessary. Instead, the neurons of these areas are recruited to enhance the
      functional connectivity between the ACC and the default mode network (DMN) to
      plan the integration of musical notes with emotion. 

PMID- 26203923
TI  - Arabidopsis AZI1 family proteins mediate signal mobilization for systemic defence
      priming.
AB  - Priming is a major mechanism behind the immunological 'memory' observed during
      two key plant systemic defences: systemic acquired resistance (SAR) and induced
      systemic resistance (ISR). Lipid-derived azelaic acid (AZA) is a mobile priming
      signal. Here, we show that the lipid transfer protein (LTP)-like AZI1 and its
      closest paralog EARLI1 are necessary for SAR, ISR and the systemic movement and
      uptake of AZA in Arabidopsis. Imaging and fractionation studies indicate that
      AZI1 and EARLI1 localize to expected places for lipid exchange/movement to occur.
      These are the ER/plasmodesmata, chloroplast outer envelopes and membrane contact
      sites between them. Furthermore, these LTP-like proteins form complexes and act
      at the site of SAR establishment. The plastid targeting of AZI1 and AZI1 paralogs
      occurs through a mechanism that may enable/facilitate their roles in signal
      mobilization. 

PMID- 26203922
TI  - Pressure-driven dome-shaped superconductivity and electronic structural evolution
      in tungsten ditelluride.
AB  - Tungsten ditelluride has attracted intense research interest due to the recent
      discovery of its large unsaturated magnetoresistance up to 60 T. Motivated by the
      presence of a small, sensitive Fermi surface of 5d electronic orbitals, we boost
      the electronic properties by applying a high pressure, and introduce
      superconductivity successfully. Superconductivity sharply appears at a pressure
      of 2.5 GPa, rapidly reaching a maximum critical temperature (Tc) of 7 K at around
      16.8 GPa, followed by a monotonic decrease in Tc with increasing pressure,
      thereby exhibiting the typical dome-shaped superconducting phase. From
      theoretical calculations, we interpret the low-pressure region of the
      superconducting dome to an enrichment of the density of states at the Fermi level
      and attribute the high-pressure decrease in Tc to possible structural
      instability. Thus, tungsten ditelluride may provide a new platform for our
      understanding of superconductivity phenomena in transition metal dichalcogenides.

PMID- 26203924
TI  - Evaluation of factors associated with loco-regional failure and survival in
      limited disease small cell lung cancer patients treated with chemoradiotherapy.
AB  - BACKGROUND: Loco-regional failure (LRF) remains a significant problem in limited
      disease small cell lung cancer (LD-SCLC) patients treated with definitive
      chemoradiotherapy. Dose-escalation may be a way forward to reduce the failure
      rate. However, the risk of toxicity rises with increasing doses. Knowledge on
      factors associated with LRF could aid the selection of patients for more
      aggressive treatment. Therefore, the aim of this study is to evaluate factors
      correlated with LRF in a cohort of LD-SCLC patients treated with definitive
      chemoradiotherapy. Moreover, factors associated with improved survival were
      investigated. MATERIAL AND METHODS: We included 147 consecutive LD-SCLC patients
      treated from 2007 to 2013. Radiotherapy was delivered as either 45 Gy in 1.5-Gy
      fractions twice daily or 46-50 Gy in 2-Gy fractions once daily. Chemotherapy was
      etoposide combined with either carboplatin or cisplatin given mainly
      concomitantly with radiotherapy. Pattern of first failure and survival were
      evaluated retrospectively. Cumulative LRF (CLRF) and overall survival (OS) were
      calculated by the Kaplan-Meier method. The impact of covariates on LRF and OS was
      evaluated by using Cox proportional hazards model. RESULTS: With a median follow
      up time of 42.2 months, 37 patients experienced LRF as first failure. Isolated
      LRF was seen in 16 patients, but no isolated regional failure was seen. The CLRF
      rate was 22% at 1-year and 43% at 3-years. N3-stage was an independent prognostic
      factor correlated with LRF development (p = 0.043). Median OS was 24.1 months
      (95% CI 19-29 months) and a three-year survival of 34%. Prognostic factors
      associated with improved OS were staging including a positron emission tomography
      (PET) scan (p = 0.004) and receiving prophylactic cranial irradiation (PCI) (p =
      0.006). CONCLUSION: N3-stage was an independent prognostic factor for LRF.
      Receiving a pretreatment PET scan and receiving PCI were prognostic factors for
      improved OS. Reduction in LRF may be achieved with dose-escalation in patients
      with N3-stage. This can be evaluated in prospective dose-escalation trials.

PMID- 26203925
TI  - Early volume variation of positive lymph nodes assessed by in-room mega voltage
      CT images predicts risk of loco-regional relapses in head and neck cancer
      patients treated with intensity-modulated radiotherapy.
AB  - BACKGROUND: We investigated the possibility to early identify non-responding
      patients based on FDG-PET positive lymph nodes (PNs) volume variation assessed
      with in-room images. MATERIAL AND METHODS: Twenty-seven head and neck cancer
      patients with at least one pre-treatment PNs were retrospectively analyzed; they
      received 54 Gy, 66 Gy, 69 Gy in 30 fractions on precautionary lymph nodal (N),
      primary (T) and PET positive (BTV) planning target volumes (PTVs), respectively
      with Helical TomoTherapy (SIB approach). PNs volume changes during treatment were
      assessed based on megavoltage computed tomography (MVCT) used for image guidance
      as ratio between volumes at fractions 10/20/30 and at first fraction. Data on T,
      N and M relapses (rT, rN, rM) were collected for all patients. The difference of
      PNs volume changes, during treatment, between patients with versus without
      relapses was tested (Mann-Whitney test). The impact of shrinkage on the
      corresponding survival curves (Cox proportional-hazard regression), dividing
      between no/moderate versus large shrinkage (based on ROC curve best cut-off
      value) was also investigated. RESULTS: Median follow-up was 27.4 m (3.7-108.9).
      The numbers for rT, rN, rM were 5, 4, 6, respectively. Differences in PNs
      shrinkage were found between patients with and without rT/rN at all considered
      timing [fr 20, rT: 0.56 vs. 1.07 (median), p = 0.06; rN: 0.57 vs. 1.25, p =
      0.07]. Differences were lower for rM. Survival curves provide high hazard ratios
      (HR) between PNs changes and rT/rN at all considered timing [fr 20, rT: best cut
      off = 0.58, HR 5.1 (95% CI 0.5-49.4), p = 0.12; rN: best cut-off = 0.98, HR 14.9
      (1.6-142.9), p = 0.01]. CONCLUSION: A limited shrinkage of PNs during treatment
      is associated with poorer outcome in terms of T/N relapses. The early variation
      of PNs observed on in-room images may provide useful information about the
      individual response with potential application in guiding an early adaptation of
      the treatment.

PMID- 26203926
TI  - Early changes in perfusion of glioblastoma during radio- and chemotherapy
      evaluated by T1-dynamic contrast enhanced magnetic resonance imaging.
AB  - BACKGROUND: The survival times of patients with glioblastoma differ widely and
      biomarkers that would enable individualized treatment are needed. The objective
      of this study was to measure changes in the vascular physiology of tumor using T1
      dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in patients with
      glioblastoma during early stages of radio- and chemotherapy (Tx) and explore
      possible correlations with treatment outcomes. MATERIAL AND METHODS: An
      exploratory prospective study was planned. Patients underwent DCE-MRI at
      baseline, after approximately one and six weeks of Tx and three and six months
      post-Tx. DCE-MRI at three Tesla generated maps of blood flow (BF), blood volume
      (BV), permeability (Ki) and volume of distribution (Vd) using a combination of
      model-free deconvolution and Patlak plots. Regions of interest in contrast
      enhancing tumor and in normal appearing white matter were contoured. Progression
      free survival (PFS) was the primary clinical outcome. Patients with PFS > 6
      months were compared with those with PFS < 6 months. Parameters of vascular
      physiology and changes in these during Tx were compared for these two groups at
      all time points using non-parametric statistics. RESULTS: Eleven eligible
      patients were included and 46 DCE-MRI examinations were carried out. BF in tumor
      increased for all patients early during Tx (p = 0.005) and then fell to a level
      below baseline at post-Tx examinations (p = 0.016). A similar but non-significant
      trend was seen for tumor BV. There was no detectable difference between patients
      with PFS > 6 months versus PFS < 6 months with regards to baseline values or
      changes during and after Tx. CONCLUSIONS: Although no correlations to outcomes
      were found, the results of this exploratory study may be hypothesis generating
      and will be examined in a larger patient group.

PMID- 26203927
TI  - Prostate displacement during transabdominal ultrasound image-guided radiotherapy
      assessed by real-time four-dimensional transperineal monitoring.
AB  - BACKGROUND: Transabdominal ultrasound (TAUS) imaging is currently available for
      localizing the prostate in daily image-guided radiotherapy (IGRT). The aim of
      this study was to determine the induced prostate displacement during such TAUS
      imaging. The prostate displacement was monitored using a novel transperineal four
      dimensional (4D) US (TPUS) system. MATERIAL AND METHODS: Ten prostate cancer
      patients, with a mean age of 68 years (58/76), were US scanned in the computed
      tomography (CT) room utilizing the Clarity 4D TPUS monitoring system. The
      patients were asked to comply with a moderate bladder filling protocol. After US
      CT fusion, the prostate volume was delineated and used as a reference for weekly
      US imaging in the treatment room. Immediately after treatment delivery the TPUS
      monitoring system was set up. During real-time monitoring of the prostate, a
      conventional 2D probe was applied to simulate a TAUS scan. The time dependent
      prostate displacements induced by the 2D probe pressure were recorded for the
      three orthogonal directions. In total 42 monitoring curves with applied 2D probe
      were recorded. RESULTS: Data analysis of 42 US scans resulted in pressure induced
      prostate displacements with mean values (+/- 1 SD) (mm); inferior (+)-superior
      (I/S): (-0.1 +/- 0.8); left (+)-right (L/R): (0.2 +/- 0.7); and anterior (+)
      posterior (A/P): (-0.1 +/- 1.0). The majority of the displacements were within 1
      2 mm. Only two scans (5%) (A/P direction) and 16% of Euclidean distances were
      larger than 2.0 mm. The largest displacement was 2.6 mm in the anterior
      direction. CONCLUSION: The novel 4D TPUS system was capable of tracking and
      recording the prostate positional displacements. The study demonstrated that the
      prostate induced displacements due to applied TAUS IGRT are small, and in most
      cases clinically irrelevant to prostate radiotherapy.

PMID- 26203928
TI  - Comparison of [18F]-FMISO, [18F]-FAZA and [18F]-HX4 for PET imaging of hypoxia--a
      simulation study.
AB  - BACKGROUND: To investigate the effect of hypoxia tracer properties on positron
      emission tomography (PET) image quality for three tracers [18F]
      fluoromisonidazole (FMISO), [18F]-fluoroazomycinarabinoside (FAZA) and [18F]
      flortanidazole (HX4), using mathematical simulations based on microscopic tumor
      tissue sections. MATERIAL AND METHODS: Oxygen distribution and tracer binding was
      mathematically simulated on immunohistochemically stained cross-sections of tumor
      xenografts. Tracer diffusion properties were determined based on available
      literature. Blood activity and clearance over a four-hour period post-injection
      (p.i.) were derived from clinical dynamic PET scans of patients suffering from
      head and neck or bronchial cancer. Simulations were performed both for average
      patient blood activities and for individual patients, and image contrast between
      normoxic and hypoxic tissue areas was determined over this four-hour period p.i.
      RESULTS: On average, HX4 showed a six-fold higher clearance than FMISO and an
      almost three-fold higher clearance than FAZA based on the clinical PET data. The
      absolute variation in clearance was significantly higher for HX4 than for FMISO
      (standard deviations of 5.75 *10-5 s-1 vs. 1.55 *10-5 s-1). The absolute tracer
      activity in these scans at four hours p.i. was highest for FMISO and lowest for
      HX4. Simulated contrast at four hours p.i. was highest for HX4 (2.39), while
      FMISO and FAZA were comparable (1.67 and 1.75, respectively). Variations in
      contrast of 7-11% were observed for each tracer depending on the vascularization
      patterns of the chosen tissue. Higher variations in clearance for HX4 resulted in
      an increased inter-patient variance in simulated contrast at four hours p.i.
      CONCLUSIONS: In line with recent experimental and clinical data, the results
      suggest that HX4 is a promising new tracer that provides high image contrast four
      hours p.i., though inter-patient variance can be very high. Nevertheless, the
      widely used tracer FMISO provides a robust and reproducible signal four hours
      p.i., but with a lower contrast. The simulations revealed tracer clearance to be
      the key factor in determining image contrast.

PMID- 26203929
TI  - Toward a more patient-specific model of post-radiotherapy saliva secretion for
      head and neck cancer patients.
AB  - BACKGROUND: Reduction of saliva secretion is a common side effect following
      radiotherapy (RT) for cancer of the head and neck region. The aim of this study
      is to predict the post-RT salivary function for individual patients prior to
      treatment and to recognise possible differences in individual radiosensitivity.
      MATERIAL AND METHODS: A predictive model for post-RT salivary function was
      validated for 64 head and neck cancer patients. The input parameters for the
      model were salivary excretion fraction (sEF) measured by 99mTc-pertechnetate
      scintigraphy, total stimulated salivary flow and mean absorbed dose for the major
      salivary glands. SEF values after RT relative to the baseline before RT (rEF)
      were compared among the patients using the distance DeltarEF between single gland
      rEF and the corresponding expected value at the dose response curve. RESULTS: A
      significant correlation (R = 0.86, p = 0.018) was found between the modelled and
      the measured values of stimulated salivary flow six months after RT. The average
      prediction error for the saliva flow rate was 6 ml/15 min. A linear relationship
      between DeltarEF for the left and the right parotid glands was observed both six
      (R = 0.53) and 12 (R = 0.79) months after RT. The average of absolute values of
      DeltarEF was 0.20 for parotid glands and 0.22 for submandibular glands.
      CONCLUSIONS: The salivary flow model was validated for 64 patients. The results
      imply, that one explanation for the discrepancies between the predicted and the
      measured salivary flow rate values and the common variations found in DeltarEF
      for the parotid glands may be differences in patients' individual response to
      radiation. However, quantitative extraction of individual radiosensitivity would
      require further studies in order to take it into account in predictive models.

PMID- 26203930
TI  - Loss of lung function after chemo-radiotherapy for NSCLC measured by perfusion
      SPECT/CT: Correlation with radiation dose and clinical morbidity.
AB  - BACKGROUND: The purpose of the study was to assess dose and time dependence of
      radiotherapy (RT)-induced changes in regional lung function measured with single
      photon emission computed tomography (SPECT) of the lung and relate these changes
      to the symptomatic endpoint of radiation pneumonitis (RP) in patients treated for
      non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: NSCLC patients
      scheduled to receive curative RT of minimum 60 Gy were included prospectively in
      the study. Lung perfusion SPECT/CT was performed before and three months after
      RT. Reconstructed SPECT/CT data were registered to treatment planning CT. Dose to
      the lung was segmented into regions corresponding to 0-5, 6-20, 21-40, 41-60 and
      > 60 Gy. Changes (%) in regional lung perfusion before and after RT were
      correlated with regional dose and symptomatic RP (CTC grade 2-5) outcome.
      RESULTS: A total of 58 patients were included, of which 45 had three-month follow
      up SPECT/CT scans. Analysis showed a statistically significant dose-dependent
      reduction in regional perfusion at three-month follow-up. The largest population
      composite perfusion loss was in 41-60 Gy (42.2%) and > 60 Gy (41.7%) dose bins.
      Lung regions receiving low dose of 0-5 Gy and 6-20 Gy had corresponding perfusion
      increase (-7.2% and -6.1%, respectively). Regional perfusion reduction was
      different in patients with and without RP with the largest difference in 21-40 Gy
      bin (p = 0.02), while for other bins the difference did not reach statistical
      significance. The risk of symptomatic RP was higher for the patients with
      perfusion reduction after RT (p = 0.02), with the relative risk estimate of 3.6
      (95% CI 1.1-12). CONCLUSION: Perfusion lung function changes in a dose-dependent
      manner after RT. The severity of radiation-induced lung symptoms is significantly
      correlated with SPECT perfusion changes. Perfusion reduction early after RT is
      associated with a high risk of later development of symptomatic RP.

PMID- 26203931
TI  - A method for evaluation of proton plan robustness towards inter-fractional motion
      applied to pelvic lymph node irradiation.
AB  - BACKGROUND: The benefit of proton therapy may be jeopardized by dose
      deterioration caused by water equivalent path length (WEPL) variations. In this
      study we introduced a method to evaluate robustness of proton therapy with
      respect to inter-fractional motion and applied it to irradiation of the pelvic
      lymph nodes (LNs) from different beam angles. Patient- versus population-specific
      patterns in dose deterioration were explored. MATERIAL AND METHODS: Patient data
      sets consisting of a planning computed tomography (pCT) as well as multiple
      repeat CT (rCT) scans for three patients were used, with target volumes and
      organs at risk (ORs) outlined in all scans. Single beam spot scanning proton
      plans were optimized for the left and right LN targets separately, across all
      possible beam angle configurations (5 degrees  angle intervals). Isotropic
      margins of 0, 3, 5 and 7 mm from the clinical target volume (CTV) to the planning
      target volume (PTV) were investigated. The optimized fluence maps for the pCT for
      each beam were applied onto all rCTs and the dose distributions were re
      calculated. WEPL variation for each beam angle was computed by averaging over
      beams eye view WEPL distributions. RESULTS: Similarity in deterioration patterns
      were found for the investigated patients, with beam angles delivering less dose
      to rectum, bladder and overall normal tissue identified around 40 degrees  and
      around 150 degrees -160 degrees  for the left LNs, and corresponding angles for
      the right LNs. These angles were also associated with low values of WEPL
      variation. CONCLUSION: We have established and explored a method to quantify the
      robustness towards inter-fractional motion of single beam proton plans treating
      the pelvic LNs from different beam configurations and with different CTV to PTV
      margins. For the patients investigated we were able to identify beam orientations
      that were robust to dose deterioration in the target and ORs.

PMID- 26203933
TI  - One year in review: the pathogenesis of rheumatoid arthritis.
AB  - The pathogenesis of rheumatoid arthritis (RA) is a complex scenario that, to
      date, is not fully elucidated. However, scientific progress has enabled us to
      understand several mechanisms underlying the development of the disease. The
      breakdown of self-tolerance in genetically predisposed individuals and the
      aberrant activation of innate and adaptive immune responses culminate in synovial
      hyperplasia and bone destruction. In addition, extra-articular manifestations, as
      well as the burden of increased cardiovascular risk (CVR), in patients with RA
      represent another interesting aspect of RA pathogenesis under intense
      investigation. The purpose of this review article is to provide an overview of
      the new insights in RA pathogenesis summarising the most relevant studies
      published over the last year. 

PMID- 26203932
TI  - Thrombotic microangiopathy and poor renal outcome in lupus patients with or
      without antiphospholipid syndrome.
AB  - OBJECTIVES: To assess the presence of acute thrombotic microangiopathy (aTMA) and
      chronic vascular lesions (cTMA) in lupus nephropathy, and to evaluate their
      association with extrarrenal lupus features, aPL positivity, antiphospholipid
      syndrome (APS) and renal survival. METHODS: We studied lupus patients with renal
      biopsy, >=1 year of post-biopsy follow-up and at least two aCL (IgG-IgM), anti
      beta2GP-I (IgG-IgM) and/or lupus anticoagulant (LAC) determinations. A blinded
      nephropathologist evaluated all biopsies. We retrospectively collected clinical,
      serological, treatment and renal survival data. We plotted survival curves and
      used Cox regression analysis. RESULTS: A total of 90 biopsies were included with
      a median disease duration 5.9 years and median follow-up 2.4 years. Eleven
      patients (12.2%) had cTMA and 3 (3%) aTMA. There was no difference in age, lupus
      duration, hypertension, drugs, APS, non-renal lupus features, low C3 or C4 aCL
      IgG, anti-beta2GP1-IgG or IgM and LAC between cTMA and non-cTMA groups. The cTMA
      group had aCL-IgM less frequently (27% vs. 66%, p=0.02), more class IV
      nephropathy (100% vs. 40%, p=0.01), higher activity index scores (7.5 vs. 2,
      p=0.03) and a tendency to need chronic dialysis (54.5% vs. 24% p=0.06). At four
      years of follow-up, 28% of the cTMA group and 62% of the non-cTMA group were free
      of dialysis (log rank p=0.03). cTMA was associated with chronic dialysis (RR 2.9,
      CI 95% 1.1-8.1, p=0.03). CONCLUSIONS: cTMA conferred a poor renal outcome. We
      found a low frequency of TMA that was not associated with with APL positivity or
      APS, suggesting that other factors hitherto not studied are involved in its
      pathogenesis.

PMID- 26203934
TI  - Late cardiac assessment in children diagnosed with post-streptococcal reactive
      arthritis: a long term study.
AB  - OBJECTIVES: Unlike rheumatic fever (RF), the association of post-streptococcal
      reactive arthritis (PSRA) and carditis is controversial. The American Heart
      Association recommends anti-streptococcal prophylaxis for PSRA for one year,
      repeating echocardiogram and discontinuation of prophylaxis if normal. In this
      study the possibility of late cardiac involvement was investigated in a cohort of
      children with PSRA. METHODS: Children diagnosed with PSRA and followed at the
      Paediatric Rheumatology Units at two medical centres in Israel had
      echocardiography carried out by a paediatric cardiologist, at least 1 year
      following diagnosis. RESULTS: 146 patients with PSRA met the study criteria. Of
      these, 69 had undergone echocardiography 1-6.9 years (mean 3.6 years +/- 1.5
      years) after diagnosis. All had normal major parameters. Twenty (29.0%) patients
      had minimal cardiac findings, including 5 (7.2%) mild mitral insufficiency, 12
      (17.4%) minimal mitral insufficiency, 2 (2.9%) mild tricuspid insufficiency and
      one patient (1.4%) had very mild, aortic insufficiency. Of the 77 patients who
      did not have echocardiography, 31 were randomly excluded from the initial study
      list, 26 refused to undergo echocardiography, and 20 were lost to follow-up. All
      were asymptomatic according to their medical record or telephone questionnaire.
      There were no significant differences in clinical or demographic data between
      those with or without echocardiography. CONCLUSIONS: No late cardiac involvement
      was found in our paediatric PSRA patients. Therefore, different approaches to
      antibiotic prophylaxis for PSRA and ARF are probably suggested. A prospective,
      controlled study is needed to definitively assess the necessity of prophylaxis in
      PSRA.

PMID- 26203935
TI  - Rats with minimal hepatic encephalopathy show reduced cGMP-dependent protein
      kinase activity in hypothalamus correlating with circadian rhythms alterations.
AB  - Patients with liver cirrhosis show disturbances in sleep and in its circadian
      rhythms which are an early sign of minimal hepatic encephalopathy (MHE). The
      mechanisms of these disturbances are poorly understood. Rats with porta-caval
      shunt (PCS), a model of MHE, show sleep disturbances reproducing those of
      cirrhotic patients. The aims of this work were to characterize the alterations in
      circadian rhythms in PCS rats and analyze the underlying mechanisms. To reach
      these aims, we analyzed in control and PCS rats: (a) daily rhythms of spontaneous
      and rewarding activity and of temperature, (b) timing of the onset of activity
      following turning-off the light, (c) synchronization to light after a phase
      advance and (d) the molecular mechanisms contributing to these alterations in
      circadian rhythms. PCS rats show altered circadian rhythms of spontaneous and
      rewarding activities (wheel running). PCS rats show more rest bouts during the
      active phase, more errors in the onset of motor activity and need less time to re
      synchronize after a phase advance than control rats. Circadian rhythm of body
      temperature is also slightly altered in PCS rats. The internal period length
      (tau) of circadian rhythm of motor activity is longer in PCS rats. We analyzed
      some mechanisms by which hypothalamus modulate circadian rhythms. PCS rats show
      increased content of cGMP in hypothalamus while the activity of cGMP-dependent
      protein kinase was reduced by 41% compared to control rats. Altered cGMP-PKG
      pathway in hypothalamus would contribute to altered circadian rhythms and
      synchronization to light. 

PMID- 26203937
TI  - Tablet and phone applications--A reflection on the experience of development.
AB  - Tablet devices are now ubiquitous. Medical illustrators have the skills to
      produce a wide range of media content. These devices offer the potential of using
      their creative abilities in new and exciting ways. There is much to explore. The
      primary difficulty lies in understanding the necessary computer technical skills
      to realise a vision. 

PMID- 26203938
TI  - Safer IV therapy: A case study on booklet design.
AB  - This case presentation introduces the work of a team of designers and how they
      collaborate to produce visually interesting teaching aids for healthcare
      professionals. 

PMID- 26203939
TI  - Dermoscopy: to cross-polarize, or not to cross-polarize, that is the question.
AB  - Dermoscopy is a non-invasive technique that visualizes the epidermal and dermal
      layers of the skin, identifying features that are not evident to the naked eye,
      making it a useful diagnostic technique in differentiating between benign and
      malignant skin lesions. There are two methods of dermoscopy, non-polarized and
      cross-polarized; both are perceived to give visual differences in lesion
      characteristics. The aim of this literature review is to identify the advantages
      and limitations between non-polarized, cross-polarized and also contact and non
      contact techniques. This research confirms that there are similarities, as well
      as differences, in the visualization of lesions between non-polarized and cross
      polarized dermoscopy. Non-polarized dermoscopy reveals superficial features and
      polarized dermoscopy shows deeper structures, concluding that the use of both
      methods can provide complementary information. 

PMID- 26203940
TI  - Assessing the sensitivity of images in research collections: A new approach at
      the Wellcome Library.
AB  - In 2014 The Wellcome Library, part of the Wellcome Trust, introduced a new policy
      in order to address research access to personal data within its collections. The
      policy has now been used by library staff for almost a year. The policy was
      devised using a multi-stage approach which consisted of internal surveys and 1:1
      interviews. Library staff can use the policy to guide decisions based on what
      level of access to award material donated or contributed to the Wellcome
      collections. The policy has been applied to 1 - a series of victorian medical
      photographs supplied by University Hospitals Bristol NHS Foundation Trust, and 2 
      an album of family photographs from the collection of the psychiatrist Dr Ann
      Dally. Following almost a year in circulation the advantages and disadvantages
      can now be summarised. 

PMID- 26203942
TI  - Illustrated & Dissected: Professor Richard Sawdon Smith.
AB  - This Alternative Gallery feature introduces the photographic artist Professor
      Richard Sawdon Smith. Professor Sawdon Smith's work stems around a fascination
      with representations of anatomy that have been fuelled by his experience as a
      hospital patient. The work has allowed him to explore ideas through the use of
      medical illustrations which include early anatomical drawings, personal medical
      photography and facial modelling. The work highlights how such imagery can be
      used in the context of a patient seeking understanding and acceptance of ill
      health and disease using the body as a canvas on which to translate the
      experience. 

PMID- 26203943
TI  - Global Perspectives.
AB  - This new professional development feature will allow professionals around the
      world to provide insight and experiential knowledge of the health science and
      communication professions in their region. The journal team want to encourage the
      sharing of experience and opportunities to promote a global understanding of how
      and where a person may develop their career in visual communication in medicine.
      We would like to encourage further submissions from a range of countries. 

PMID- 26203944
TI  - Medical and Scientific Illustration in the United States (US).
AB  - The field of Medical and Scientific Illustration in the United States is large
      and constantly changing. In 1974, when the author began his studies, everything
      about the field was different. At the time, a student in the U.S. could go to a
      number of Universities (4 year) or Colleges (2 year) to study this subject. More
      than forty years later, only a few programs still offer similar programs of
      study. The Rochester Institute of Technology (RIT), where the author is a
      professor and Randolph Community College in North Carolina are all that remain
      from the more than ten that had operated. These two programs are very different
      from one another and there is not adequate space in this article to expand on
      these differences. Program details can be found online at:
      http://cias.rit.edu/schools/photographic-arts-sciences/undergraduate-biomedical
      photographic-communications. 

PMID- 26203945
TI  - Slit lamp photography: The basics.
AB  - This introductory paper is designed to explain the basics of slit lamp
      photography with the use of illustrations and sample images. The two primary
      methods of illumination are described with reference to positioning and
      magnification, as well as the use of background illumination. Filters and dye
      usage are described along with a brief explanation of associated imaging
      techniques. Further explanation of techniques will be looked at in subsequent
      articles, this paper aims to give an over view rather than an in-depth discussion
      of techniques. 

PMID- 26203949
TI  - Death cafes: a place where students can talk too.

PMID- 26203950
TI  - Developing palliative care globally: facing the challenge.

PMID- 26203951
TI  - Hospice nurses' views on single nurse administration of controlled drugs.
AB  - BACKGROUND: The involvement of two nurses to dispense and administer controlled
      drugs is routine practice in most clinical areas despite there being no legal or
      evidence-based rationale. Indeed, evidence suggests this practice enhances
      neither safety nor care. Registered nurses at two hospices agreed to change
      practice to single nurse dispensing and administration of controlled drugs
      (SNAD). Participants' views on SNAD were evaluated before and after
      implementation. The aim of this study was to explore the views and experiences of
      nurses who had implemented SNAD and to identify the views and concerns of those
      who had not yet experienced SNAD. METHOD: Data was obtained through semi
      structured interviews. RESULTS: Qualitative thematic analysis of interview
      transcripts identified three key themes: practice to enhance patient benefit and
      care; practice to enhance nursing care and satisfaction; and practice to enhance
      organisational safety. CONCLUSION: The findings have implications for the
      understanding of influences on medicines safety in clinical practice and for
      hospice policy makers.

PMID- 26203952
TI  - Syringe drivers: their key safety features.

PMID- 26203953
TI  - An evaluation of a palliative care outreach programme for children with Burkitt
      lymphoma in rural Cameroon.
AB  - BACKGROUND: Palliative care (PC) is the most appropriate treatment for patients
      with life-limiting, incurable diseases, but it is a relatively new concept in sub
      Saharan Africa (SSA). A lack of curative treatment options for some conditions
      creates a great need for PC, but such services are rarely provided in SSA. More
      research into PC in SSA is urgently needed to create an evidence base to confirm
      the importance of appropriate PC services. OBJECTIVES: To gain a better
      understanding of the needs of patients and their families visited by a children's
      PC nurse in Cameroon and to identify aspects of the service that can be improved.
      METHODOLOGY: A qualitative study design with semi-structured interviews was used.
      Tape-recorded interviews were transcribed and thematically analysed. RESULTS:
      Twelve interviews were conducted with patients, carers and nurses. Financial aid,
      general disease improvement and prayers were the directly expressed needs of
      service recipients. Specialist training in children's PC was the main need
      expressed by the nurses. Open communication about clinical status and treatment
      failure, more detailed counselling, more distraction for patients and respite for
      carers were identified as underlying needs. CONCLUSION: It is possible to provide
      an effective children's PC service that meets the most urgent needs of recipients
      in a rural setting in SSA. Recommendations include improved counselling,
      specialist education for staff, expansion of local support networks and more
      frequent home visits. More studies are needed to help define the need for PC in
      children with life-limiting diseases.

PMID- 26203954
TI  - The role of dance movement psychotherapy for expression and integration of the
      self in palliative care.
AB  - AIM: To explore clients' experiences of dance movement psychotherapy (DMP) in a
      day hospice setting. BACKGROUND: DMP is a creative arts therapy, enabling people
      to use movement to express themselves and promote physical, emotional, social and
      spiritual wellbeing. This is the first known research about DMP in palliative
      care in the UK. METHODS: A case study approach explored four clients' experiences
      of DMP in depth. RESULTS: Participants' ill bodies had become obstacles to them
      expressing their sense of self. The safe therapeutic conditions, gentle movement,
      music, words and props in DMP enabled them to express interconnected physical and
      emotional pain and loss of sense of self. DMP enabled them to reintegrate with
      their estranged bodies, releasing tension by expressing themselves as a whole
      person. CONCLUSION: Wider practice of DMP could relieve holistic pain by enabling
      people with terminal illnesses to express a complete sense of who they are as a
      human being.

PMID- 26203955
TI  - Factors associated with acute care use among nursing home residents dying of
      cancer: a population-based study.
AB  - BACKGROUND: Little is known about residents of long-term care (LTC) facilities
      who die of cancer. The authors examined factors among this cohort prognostic of
      greater acute care use to identify areas for improving support in LTC. METHODS:
      The authors used administrative data representing all cancer decedents in
      Ontario, Canada, who had been living in LTC. Binary logistic regression was used
      to examine the contribution of covariates to having an emergency department (ED)
      visit in the last 6 months of life or to death in hospital. RESULTS: Among the
      1196 LTC residents in the study cohort, 61% had visited an ED in the last 6
      months of life and 20% had died in hospital. Cancer type, income, gender, time in
      LTC and rural location were not strong predictors of the acute care outcomes.
      However, certain comorbidities, being younger and region of residence
      significantly increased the odds of an ED visit and/or hospital death (all
      P<0.05). CONCLUSIONS: Determining the characteristics of LTC patients more likely
      to access acute care services can help to inform interventions that avoid costly
      and potentially adverse transfers to hospital. The study of cancer patients in
      LTC represents a starting point for clarifying the potential of specialised
      palliative care nursing and other support that is often lacking in these
      facilities.

PMID- 26203958
TI  - A novel bedside diagnostic test for methanol poisoning using dry chemistry for
      formate.
AB  - BACKGROUND: The standard diagnostic approach to methanol poisoning is
      chromatographic measurement of methanol on centrally placed stationary equipment.
      Methanol poisoning in places where such equipment is unavailable is thus often
      not diagnosed. Methanol is metabolized to a toxic metabolite, formate; the
      presence of this compound indicates methanol poisoning. We have developed an
      enzymatic test for formate and modified it into a portable dry chemistry system
      that could be used anywhere. METHODS: The method consists of two enzymatic steps:
      Formation of NADH from NAD by formate dehydrogenase, and subsequent use of NADH
      as a reductant of a tetrazolium into a formazan dye that can be quantified
      photometrically or visually. RESULTS: The photometer gave a good correlation of
      R(2) = 0.9893 in serum and R(2) = 0.9949 in whole blood, showing an instrumental
      detection limit of less than 1 mM (4.5 mg/dL). The visual readings showed a
      correlation of R(2) = 0.8966. Users experienced some difficulty in separating the
      negative control from the low positives. CONCLUSIONS: We have documented the
      feasibility of an affordable formate strip test for bedside diagnosis of methanol
      poisoning and for screening of metabolic acidosis of unknown origin. Visual
      reading is possible, but a reader will improve reliability at lower levels of
      formate. Future studies are necessary to study the sensitivity and specificity
      towards other causes of metabolic acidosis and other acids present in human
      blood.

PMID- 26203959
TI  - Causes of hypoamylasaemia in a hospital population.
AB  - AIMS: We noted serum amylase activity results in our laboratory that fell below
      the lower reference limit, although there was no obvious explanation for this and
      the literature on this topic is relatively sparse. METHODS: We studied hospital
      laboratory requests and reports of individuals showing hypoamylasaemia over a one
      year period. RESULTS: We report one of the few studies to look at hypoamylasaemia
      in a hospital population. We found that 5.4% of the hospital serum amylase
      activity results were below the reference range quoted by our laboratory.
      CONCLUSIONS: Some of the associations we observed with hypoamylasaemia were
      diabetes mellitus, cystic fibrosis, hypertriglyceridaemia and use of the
      antibiotic gentamicin. We suggest that clinicians and laboratories should be
      aware of the causes of hypoamylasaemia to aid interpretation of abnormally low
      amylase activity in their patients.

PMID- 26203961
TI  - ?

PMID- 26203960
TI  - Preprocedural N-terminal pro-B-type natriuretic peptide as a useful marker for
      predicting periprocedural myocardial injury following percutaneous coronary
      intervention in diabetic patients without cardiac dysfunction.
AB  - BACKGROUND: Elevated preprocedural N-term pro-B-type natriuretic peptide (NT-pro
      BNP) and postprocedural cardiac troponin I (cTnI) are related to a poor cardiac
      outcome in the non-diabetic population. We hypothesized that preprocedural NT-pro
      BNP might be a useful marker in predicting periprocedural myocardial injury (PMI)
      following elective percutaneous coronary intervention (PCI) in type 2 diabetes
      (T2D). METHODS: We prospectively enrolled 1194 consecutive diabetic patients with
      normal cardiac function and preprocedural cTnI who were successfully undergoing
      elective PCI. Preprocedural NT-pro-BNP levels were assessed at admission, and PMI
      was evaluated by analysis of cTnI within 24 hours. The relationship between
      preprocedural NT-pro-BNP levels and the peak values of cTnI after PCI was
      examined. RESULTS: Patients with high baseline NT-pro-BNP levels had higher
      postprocedural cTnI levels (beta = 0.123, p < 0.001). In the multivariable model,
      NT-pro-BNP was associated with higher risk of postprocedural cTnI elevation above
      1 * upper limit of normal (ULN, OR, 3.13; 95% CI, 1.51-6.50; p = 0.002), 3 * ULN
      (OR, 2.44; 95% CI, 1.17-5.08; p = 0.018), 5 * ULN (OR, 3.18; 95% CI, 1.44-7.0; p
      = 0.004), respectively. Moreover, the incidence of cTnI elevation was higher in
      patients with the upper tertile of NT-pro-BNP levels than that in ones with the
      lower tertile of NT-pro-BNP levels (> 1 * ULN: 63.1% vs. 50.0%, p < 0.001; > 3 *
      ULN: 39.2% vs. 31.9%, p = 0.032; > 5 * ULN: 30.4% vs. 21.9%, p < 0.006;
      respectively). CONCLUSIONS: Our data, for the first time, demonstrated that
      increased preprocedural NT-pro-BNP levels were strongly and independently
      associated with a higher risk of PMI, suggesting that baseline NT-pro-BNP level
      might be a useful marker for predicting PMI following PCI in diabetic patients
      without cardiac dysfunction.

PMID- 26203962
TI  - ?

PMID- 26203963
TI  - ?

PMID- 26203964
TI  - ?

PMID- 26203965
TI  - ?

PMID- 26203966
TI  - Heritability of ambulatory and office blood pressure in the Swiss population.
AB  - BACKGROUND: Blood pressure (BP) is known to aggregate in families. Yet,
      heritability estimates are population-specific and no Swiss data have been
      published so far. We estimated the heritability of ambulatory and office BP in a
      Swiss population-based sample. METHODS: The Swiss Kidney Project on Genes in
      Hypertension is a population-based family study focusing on BP genetics. Office
      and ambulatory BP were measured in 1009 individuals from 271 nuclear families.
      Heritability was estimated for SBP, DBP, and pulse pressure using a maximum
      likelihood method implanted in the Statistical Analysis in Genetic Epidemiology
      software. RESULTS: The 518 women and 491 men included in this analysis had a mean
      (+/-SD) age of 48.3 (+/-17.4) and 47.3 (+/-17.7) years, and a mean BMI of 23.8
      (+/-4.2) and 25.9 (+/-4.1) kg/m, respectively. Narrow-sense heritability
      estimates (+/-standard error) for ambulatory SBP, DBP, and pulse pressure were
      0.37 +/- 0.07, 0.26 +/- 0.07, and 0.29 +/- 0.07 for 24-h BP; 0.39 +/- 0.07, 0.28
      +/- 0.07, and 0.27 +/- 0.07 for day BP; and 0.25 +/- 0.07, 0.20 +/- 0.07, and
      0.30 +/- 0.07 for night BP, respectively (all P < 0.001). Heritability estimates
      for office SBP, DBP, and pulse pressure were 0.21 +/- 0.08, 0.25 +/- 0.08, and
      0.18 +/- 0.07 (all P < 0.01). CONCLUSIONS: We found significant heritability
      estimates for both ambulatory and office BP in this Swiss population-based study.
      Our findings justify the ongoing search for the genetic determinants of BP.

PMID- 26203967
TI  - Impaired endothelium-dependent vasodilation does not initiate the development of
      sunitinib-associated hypertension.
AB  - BACKGROUND: Tyrosine kinase inhibitors targeting angiogenesis have become an
      important part of the treatment of patients with several types of cancer. One of
      the most reported side effects of vascular endothelial growth factor receptor
      (VEGFR)-targeted therapies is hypertension. In this study, we hypothesized that
      the development of hypertension in patients treated with sunitinib, a
      multitargeted tyrosine kinase inhibitor, is preceded by reduced endothelium
      dependent vasodilation. Moreover, we hypothesized that this endothelial
      dysfunction is a result of impaired nitric oxide release. METHOD: In a placebo
      controlled experiment, we determined vascular responses in isolated mesenteric
      arteries of rats (n = 26) after 7 days of sunitinib treatment. RESULTS: Sunitinib
      reduced endothelium-dependent vasodilation, but not endothelium-independent
      vasodilation. Moreover, we observed that the difference in endothelium-dependent
      vasodilation between controls and sunitinib-treated animals disappeared in the
      presence of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide antagonist.
      In patients with metastatic renal cell carcinoma, before and 1 week after start
      of sunitinib, the endothelium-dependent vasodilator response to intra-arterial
      acetycholine and the endothelium-independent vasodilator response to intra
      arterial sodium nitroprusside was assessed with venous occlusion plethysmography.
      No changes in forearm blood flow ratios were observed. Mean arterial pressure did
      significantly increase from 101.9 +/- 3.8 to 106.1 +/- 2.6 mmHg after 1 week and
      further to 115.8 (+/-4.9) mmHg after 2 weeks of treatment. CONCLUSION: In
      animals, this study confirms that exposure to high concentrations of sunitinib
      reduces endothelium-dependent vasodilation by reducing endothelial release of
      nitric oxide. In humans, however, reduced endothelium-dependent vasodilation does
      not precede the development of hypertension in patients treated with sunitinib.

PMID- 26203968
TI  - Particulate matter air pollution and ambient temperature: opposing effects on
      blood pressure in high-risk cardiac patients.
AB  - OBJECTIVE: Fine particulate matter air pollution (PM2.5) and extreme temperatures
      have both been associated with alterations in blood pressure (BP). However, few
      studies have evaluated their joint haemodynamic actions among individuals at high
      risk for cardiovascular events. METHODS: We assessed the effects of short-term
      exposures during the prior week to ambient PM2.5 and outdoor temperature levels
      on resting seated BP among 2078 patients enrolling into a cardiac rehabilitation
      programme at the University of Michigan (from 2003 to 2011) using multiple linear
      regression analyses adjusting for age, sex, BMI, ozone and the same-day alternate
      environmental factor (i.e. PM2.5 or temperature). RESULTS: Mean PM2.5 and
      temperature levels were 12.6 +/- 8.2 MUg/m and 10.3 +/- 10.4 degrees C,
      respectively. Each standard deviation elevation in PM2.5 concentration during lag
      days 4-6 was associated with significant increases in SBP (2.1-3.5 mmHg) and DBP
      (1.7-1.8 mmHg). Conversely, higher temperature levels (per 10.4 degrees C) during
      lag days 4-6 were associated with reductions in both SBP (-3.6 to -2.3 mmHg) and
      DBP (-2.5 to -1.8 mmHg). There was little evidence for consistent effect
      modification by other covariates (e.g. demographics, seasons, medication usage).
      CONCLUSION: Short-term exposures to PM2.5, even at low concentrations within
      current air quality standards, are associated with significant increases in BP.
      Contrarily, higher ambient temperatures prompt the opposite haemodynamic effect.
      These findings demonstrate that both ubiquitous environmental exposures have
      clinically meaningful effects on resting BP among high-risk cardiac patients.

PMID- 26203969
TI  - Can blood pressure-lowering therapy reduce the risk of cognitive decline in the
      elderly?

PMID- 26203970
TI  - Update on the treatment of chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - PURPOSE OF REVIEW: Chronic inflammatory demyelinating polyradiculoneuropathy
      (CIDP) is a chronic and often disabling neuropathy, which often responds to
      immune therapies including corticosteroids, plasma exchange, and high-dose
      intravenous immunoglobulin (IVIg). The reasons for choosing one of these
      therapies and the factors that may predict response to these therapies remain,
      however, unclear. It is also unclear whether other immune therapies may be useful
      in CIDP. We will here review the studies addressing these points in CIDP. RECENT
      FINDINGS: Recent studies have shown that IVIg are initially more frequently
      effective than steroids in CIDP even if steroids, when effective, have a more
      prolonged efficacy. Some clinical and immunological features including the
      presence of antibodies against proteins at the nodes of Ranvier were associated
      with specific response to therapy even if the data need to be confirmed in large
      series of patients. A few anecdotal studies also reported the efficacy in some
      patients of new immune therapies whose efficacy needs to be confirmed in
      controlled trials. SUMMARY: IVIg are initially more frequently effective than
      steroids in CIDP, but the latter have a more prolonged efficacy. Some clinical
      presentations and their association with specific antibodies reactions may help
      in predicting the response to specific treatment. The possible benefit of new
      immune therapies await confirmation from randomized studies.

PMID- 26203971
TI  - Psychoacoustic analysis of noise and the application of earplugs in an ICU: A
      randomised controlled clinical trial.
AB  - BACKGROUND: Patients and medical staff are exposed to high noise levels in ICUs,
      which may have a negative impact on their health. Due to the diversity of noise
      sources present, including the operating noise of medical devices, staff
      conversations and the unwrapping of disposables, noise profiles are varied.
      Psychoacoustics deals with the analysis of sound, focusing on its effects on
      physiological perception and stress. OBJECTIVES: The aim of our study was to
      examine and to classify noise and its psychoacoustic properties in different
      locations in our ICU at different times. The impact of noise on subjective
      parameters and stress-related physiological data was also assessed with and
      without interventional methods. DESIGN: A randomised, controlled, single-blinded
      clinical trial. SETTING: University Hospital, from November 2010 to May 2011.
      PATIENTS: One hundred and forty-four patients in the ICU. INTERVENTIONS: In the
      first part, multidisciplinary psychoacoustic measurement was performed on the
      patients in our ICU. In the subsequent clinical trial, patients were equipped
      with effective earplugs, less effective earplugs and no earplugs. Thereafter,
      active noise cancellation headphones with or without sound masking were employed
      on a third patient population. MAIN OUTCOME MEASURES: Cortisol and alpha-amylase
      in saliva, skin conductance measures, vital signs, psychoacoustic analyses and
      two standardised questionnaires [State-Trait Anxiety Inventory (STAI) and
      Hospital Anxiety and Depression Scale (HADS)] were assessed. RESULTS: In the
      first part, the mean +/- standard deviation (SD) subjective loudness was 9.2 +/-
      4.0 sone. Although absolute sound pressure level and loudness were lower during
      the night, the number of loud events increased significantly. Skin conductance in
      the earplug groups was significantly reduced in comparison to that in the control
      population but not the active noise reduction groups. Nevertheless, noise
      reduction was found to be comfortable for most patients. CONCLUSION: Noise in the
      ICU is of high clinical relevance. Diverse noise reduction methods, such as
      earplugs and active noise cancellation, are available. The avoidance of
      unnecessary noise, however, should be the primary focus. TRIAL REGISTRATION:
      German Clinical Trials Register (DRKS00000534).

PMID- 26203972
TI  - Surgical procedure and postoperative delirium in geriatric hip fracture patients.

PMID- 26203977
TI  - The International Aesthetic Conference: What to Expect.

PMID- 26203978
TI  - Pediatric Nail-Bed Repair Study: Part 2. Fact or Fixation?

PMID- 26203979
TI  - A Physiologic Pain Pump for Abdominoplasty: An Alternative to Regional Blocks and
      Liposomal Bupivacaine.

PMID- 26203980
TI  - Quality Care and the Plastic Surgeon's Role in the Treatment of Skin Lesions.

PMID- 26203981
TI  - Comments on A systematic review comparing Furlow double-opposing Z-plasty and
      straight-line intravelar veloplasty methods of cleft palate repair: Double
      opposing Z-plasty and straight-line.

PMID- 26203982
TI  - Professor Zbigniew (Bob) Kabata (1924-2014).

PMID- 26203983
TI  - Antiparasitic DNA vaccines in 21st century.
AB  - Demands for effective vaccines to control parasitic diseases of humans and
      livestock have been recently exacerbated by the development of resistance of most
      pathogenic parasites to anti-parasitic drugs. Novel genomic and proteomic
      technologies have provided opportunities for the discovery and improvement of DNA
      vaccines which are relatively easy as well as cheap to fabricate and stable at
      room temperatures. However, their main limitation is rather poor immunogenicity,
      which makes it necessary to couple the antigens with adjuvant molecules. This
      paper review recent advances in the development of DNA vaccines to some
      pathogenic protozoa and helminths. Numerous studies were conducted over the past
      14 years of 21st century, employing various administration techniques, adjuvants
      and new immunogenic antigens to increase efficacy of DNA vaccines. Unfortunately,
      the results have not been rewarding. Further research is necessary using more
      extensive combinations of antigens; alternate delivery systems and more efficient
      adjuvants based on knowledge of the immunomodulatory capacities of parasitic
      protozoa and helminths. 

PMID- 26203984
TI  - Evaluation of Eimeria krijgsmanni as a murine model for testing the efficacy of
      anti-parasitic agents.
AB  - Murine Eimeria spp. have been used as effective models of disease instead of
      large mammalian hosts such as cattle. We attempted to establish in vivo and in
      vitro assays using a murine intestinal protozoan, Eimeria krijgsmanni, which we
      previously isolated, to test anti-parasitic agents. Consequently, when mice were
      treated with sulfur drugs or toltrazuril, which are commercially available for
      livestock. Furthermore, sporulated oocysts and excysted sporozoites of E.
      krijgsmanni were treated with naturally occurring substances (lactoferrin,
      longicin, and curcumin). Although exposure to these substances did not affect
      oocyst infectivity, sporozoite viability decreased by 60% with longicin. However,
      direct injection of sporozoites treated with longicin into mice ceca did not
      result in any changes in the oocyst shedding pattern compared with control mice.
      The results suggest that E. krijgsmanni could be resistant to these anti
      parasitic agents and might therefore have different characteristics to other
      apicomplexan parasites. 

PMID- 26203985
TI  - First record of parasitism of water mite larva (Acari: Hydrachnidia) on the pupa
      of Trichoptera.
AB  - During the studies on ecology of Trichoptera of anthropogenic water bodies we
      have unexpectedly discovered the parasitic larvae of water mites of the species
      Tiphys torris on the pupa of Triaenodes bicolor. This is the first documented
      case of the parasitism of water mites on the caddisfly pupa as well as the first
      ever record of the species which is regarded as a dipteran parasite on
      caddisflies. The situation is very untypical for preimaginal stages of
      caddisflies are used by phoretic and not parasitic water mite larvae. Parasitism
      has been confirmed in this case by the formation of stylostomes and enlarged
      sizes of the bodies of the larvae. This is probably the case of facultative
      parasitism in which the pupa has served as a substitute of the adult form of a
      caddisfly. 

PMID- 26203986
TI  - Ultrastructural characterization of Acarispora falculifera n.gen., n.sp., a new
      microsporidium (Opisthokonta: Chytridiopsida) from the feather mite Falculifer
      rostratus (Astigmata: Pterolichoidea).
AB  - Only about 20 species of microsporidia have been described from mites. All except
      one species produce typical spores with a long polar filament and a polaroplast.
      This paper is the first study of an atypical microsporidium infection in a
      feather mite (Falculifer rostratus). The infection of the pigeon feather mite is
      restricted to the colon epithelium where it leads to hypertrophy of the concerned
      cells. During sporogony, a multinucleate plasmodial aggregate is formed within a
      sporont (endogenous sporogony resulting in a polysporophorous vesicle). The
      cisterns delimiting the single sporoblasts later form the spore walls.
      Sporogonial stages are in direct contact to the host cell cytoplasm. Merogonial
      stages were not present. Spores are tiny (3.6 MUm * 2.6 MUm), broad oval in form
      and monokaryotic. The spore wall of mature spores consists of a three-layered
      endospore and a thin, electron-dense, wavy exospore. The polar filament is
      anisofilar and completely coiled in 3-4 turns. In cross-sections, it has a star
      like appearance because the electron-dense core forms rounded compartments of
      lucent material at its surface. In superficial sections, this results in a
      honeycomb-like pattern. A polaroplast is missing. The polar filament arises
      subapically at a polar sac that lacks an internal anchoring disk. These atypical
      spore structures clearly classify the species from the feather mite as a member
      of the order Chytridiopsida. It could not be clearly affiliated to one of the
      known genera, so we created a new genus, Acarispora, with the species A.
      falculifera. 

PMID- 26203987
TI  - Molecular diagnosis of natural fasciolosis by DNA detection in sheep faeces.
AB  - Fasciolosis is an important parasitic zoonosis considered the most important
      helminth infection of ruminants in tropical countries. The aim of this study was
      to develop a PCR assay for the sensitive and specific detection of F. hepatica in
      formalin preserved sheep faeces. A 405-bp fragment of the cytochrome c oxidase
      subunit 1 gene of F. hepatica was amplified from stool samples of infected sheep.
      The PCR assay showed a detection limit of 20 pg of F. hepatica DNA. No cross
      reactions were observed with samples containing coccidian oocysts or
      gastrointestinal nematodes eggs. Our PCR technique showed to be effective for
      specific detection of F. hepatica infections in sheep. 

PMID- 26203989
TI  - Two Procamallanus (Spirocamallanus) species (Nematoda: Camallanidae) from
      freshwater fishes in the Lower Congo River.
AB  - Based on light and scanning electron microscopical studies, one known and one
      previously undescribed Procamallanus (Spirocamallanus) species (Nematoda:
      Camallanidae) are described from specimens collected in the intestine of
      freshwater fishes in the Lower Congo River, Democratic Republic of Congo: P. (S.)
      daleneae (Boomker 1993) from Synodontis acanthomias Boulenger (Mochokidae,
      Siluriformes) (new host and geographical records) and P. (S.) parachannae sp.
      nov. from Parachanna insignis (Sauvage) (Channidae, Perciformes). The new species
      is most similar to P. (S.) serranochromis Moravec et Van As 2015, a parasite of
      African cichlids (Serranochromis spp.), differing from it mainly in the absence
      of any outgrowths on the female tail tip, a distinctly longer (546 MUm) right
      spicule, a different length ratio of both spicules (1:2.6) and in the morphology
      of fourth-stage larvae. P. (S.) daleneae, a specific parasite of squeakers
      (Synodontis spp.), is redescribed; in contrast to the original description, the
      number of postanal papillae was found to be identical (6 pairs) with that of
      other related species. 

PMID- 26203990
TI  - Description of a new species of Podocotyle Dujardin, 1845 (Digenea: Opecoelidae:
      Plagioporinae) from the cusk-eel, Luciobrotula corethromycter Cohen, 1964
      (Ophidiiformes: Ophidiidae), from the Gulf of Mexico and Caribbean Sea.
AB  - Podocotyle bathyhelminthos n. sp. (Opecoelidae: Plagioporinae) is described from
      the cusk-eel, Luciobrotula corethromycter Cohen, 1964 (Ophidiiformes:
      Ophidiidae), collected at depths of 622-1,280 m in the northern Gulf of Mexico
      and Caribbean Sea off Colombia. The new species is distinguished by possessing a
      combination of the following features: an elongate oval body shape, a sucker
      width ratio of 1:1.4-1.9, deeply lobed and irregularly-shaped testes, a cirrus
      sac that extends just in to the hindbody, a trilobed ovary and vitellarium that
      extend to the ventral sucker level. Several unique features in P. bathyhelminthos
      n. sp. were not present in all, or almost all, recognized species of Podocotyle
      including a conspicuous deep cleft at the posterior end of the worm, a small
      transverse ridge on the ventral surface immediately anterior to the ventral
      sucker, uterine loops extending ventral to the caeca and, at times, lateral to
      the caeca, a thick-walled metraterm extending 1/3 to 1/2 the length of the cirrus
      sac and P. bathyhelminthos n. sp. parasitizes a deep water piscine host.
      Podocotyle etheostomae Aliff, 1973 is declared a nomen nudum. A brief discussion
      of Podocotyle Dujardin, 1845 in deep waters is presented, and a gastropod,
      caridean shrimp and cusk-eel are hypothesized as hosts in the life cycle of P.
      bathyhelminthos n. sp. in the deep sea. 

PMID- 26203988
TI  - Frequencies of dhfr/dhps multiple mutations and Plasmodium falciparum
      submicroscopic gametocyte carriage in Gabonese pregnant women following IPTp-SP
      implementation.
AB  - This study analyzed the relationship between intermittent preventive treatment
      with sulfadoxine-pyrimethamine (SP) (IPTp-SP), the rate of multiple resistant
      parasites and of submicroscopic gametocyte carriage among pregnant women at the
      beginning of IPTp implementation in Gabon (2005) and six years after (2011). The
      detection of pfdhfr and pfdhps gene mutations was performed by PCR-RFLP in
      Plasmodium (P.) falciparum positive samples collected from pregnant women in 2005
      and 2011. Gametocytes carriage was detected by Pfs25mRNA amplification using QT
      NASBA. Data were analyzed according to the time of collection (study period) and
      IPTp-SP doses. The proportion of isolates with at least a triple Pfdhfr mutation
      (n = 39/42, 92.9% versus 100%, n = 78/78)) and of those isolates with the
      S108N/C59R/N51I/S436A/A437G multiple mutation (17.9% versus 75.6%) significantly
      increased between 2005 and 2011 (p<0.01). Mutations I164L and A581G were not
      found, while higher proportions of 436 and 437 mutations were detected in 2011.A
      trend toward a higher frequency of isolates with five mutations was observed in
      women who received two SP doses (p<0.01). Pfs25mRNA was found in 6.8 % (n = 3/44)
      and 34.6% (n = 27/78) of the samples collected in 2005 and 2011 respectively
      (p<0.01). In 2011, 74.0% (n = 20/27) of women with detected submicroscopic
      gametocytes carried parasites with the S108N/C59R/N51/S436A/A437G multiple
      mutation. All the ten delivering women who received three IPTp-SP doses had a
      submicroscopic Plasmodium falciparum infection, but none had detected
      gametocytes. Following IPTp-SP implementation, an increase in the frequency of
      multiple mutant parasites and of submicroscopic gametocyte carriage was observed
      among pregnant women living in Gabon. 

PMID- 26203991
TI  - Preliminary analysis of Plasmodium vivax genotypes isolated in southeastern
      Turkey.
AB  - Plasmodium vivax is the most common cause of malaria worldwide as well as
      southeastern Turkey. After the implementation of a successful national
      elimination program that the local malaria cases were not reported in 2011,
      malaria returned to county of Savur located in southeastern Turkey in summer of
      2012. The present study aimed to determine the prevalent P. vivax genotypes
      isolated from southeastern Turkey. Genetic polymorphism in P. vivax CSP gene was
      analyzed by PCR-RFLP to assess the ratio of VK210 and VK247 types. Blood samples
      were obtained from 15 patients who lived in southeastern between 2005-2006.
      According to the results, VK210 type was detected in 10 samples (66.6%), VK247
      type was observed in three samples (20%). Remaining two samples showed mixed
      infection (13.3%). The results of the present study first time showed the ratio
      of P. vivax genotypes in southeastern Turkey before the elimination in 2011. The
      results of the present study will be enable researchers to compare the new
      isolates with the previously detected ones and design new treatment
      and/elimination strategies. 

PMID- 26203992
TI  - A new species of the feather mite genus Dubininia Vassilev, 1958 (Acari:
      Xolalgidae) from the Black-thighed Falconet Microhierax fringillarius
      (Falconiformes: Falconidae).
AB  - A new feather mite species Dubininia microhieracis sp. n. (Analgoidea:
      Xolalgidae) is described from the Black-thighed Falconet Microhierax
      fringillarius (Drapiez) (Falconiformes: Falconidae) from Java. This is the second
      species of the genus Dubininia found on falconiform hosts; most known species of
      this genus are associated with parrots (Psittaciformes). 

PMID- 26203993
TI  - First data on the parasites of Hoplias aimara (Characiformes): description of two
      new species of gill monogeneans (Dactylogyridae).
AB  - The first data on the parasites of the giant trahira, Hoplias aimara
      (Characiformes: Erythrinidae), a little known, but popular fish for sport
      angling, are provided. In H. aimara from the Xingu River in Brazil, two new
      species of gill monogeneans of the family Dactylogyridae were found and their
      description is provided herein. Urocleidoides aimarai n. sp. differs from all 18
      congeners by the presence of a large accessory piece of the male copulatory organ
      and based by morphology of anchors. Urocleidoides xinguensis n. sp. is
      distinguished by unique combination of copulatory complex and haptoral
      structures. 

PMID- 26203994
TI  - On a new species of Cosmocerca (Nematoda: Cosmocercidae) from Microhyla rubra
      (Anura: Microhylidae) from West Bengal, India.
AB  - Cosmocerca microhylae sp. nov., recovered from the rectum of a red narrow-mouthed
      frog, Microhyla rubra (Jerdon, 1854) (Anura: Microhylidae), collected from Bolpur
      in the Birbhum district of West Bengal, India, is described and figured. This
      species is similar to C. acanthurum, C. banyulensis, C. cruzi, C. japonica, C.
      kalesari, C. novaeguineae, C. ornata, C. paraguayensis, C. parva, C. podicipinus
      and C. travassosi in having 5 pairs of plectanes supporting preanal papillae but
      differs from these species by smaller size, absence of somatic papillae in
      females and having only one pair of adanal papillae in males and one pair
      postanal papillae in females. Cosmocerca microhylae sp. nov. represents 27th
      species assigned to the genus, and 4th species from India. 

PMID- 26203995
TI  - First report of Hepatozoon (Apicomplexa: Adeleorina) from king ratsnakes (Elaphe
      carinata) in Shanghai, with description of a new species.
AB  - Hepatozoon species are the most common hemoparasites of snakes. In this study,
      Hepatozoon parasites were examined for the first time in king rat snakes (Elaphe
      carinata) from Shanghai, China. All 10 snakes were found to be infected with
      Hepatozoon gamonts. The gamonts were folded back in a hook-wise fashion for about
      3 MUm at one end. Parasitemia levels ranged from 4-43 infected erythrocytes per
      1,000 examined. The gamonts changed the morphology of the parasitized
      erythrocytes. Although the gamonts showed some distinct variations in both the
      parasite and its nucleus, phylogenetic analysis indicated that all the E.
      carinata in this study formed a monophyletic group, and were distinct from all
      other published Hepatozoon species. A new species, Hepatozoon chinensis, was
      proposed based on the molecular and morphologic evidence. 

PMID- 26203996
TI  - Seroepidemiological study of Neospora caninum in beef and dairy cattle in La
      Pampa, Argentina.
AB  - Neospora caninum is considered one of the major causes of abortion in cattle. The
      aim of this study was to examine and quantify the extent of the infection in
      cattle in a representative region of Argentina (La Pampa, province). An average
      sample size of 36 sera per herd was selected from 97 beef and 24 dairy herds. A
      total of 4334 serum samples were tested for specific anti- Neospora caninum IgG
      using an indirect-ELISA and 302 seropositive-ELISA sera were re-examined using an
      Avidity-ELISA procedure for N.caninum. The overall estimated seroprevalence for
      N.caninun was 9.6% (95%CI: 8.7%; 10.5%). Levels of seroprevalence were
      significantly different in beef 7.0% and dairy 20.3% cattle. Disease distribution
      seems to be associated with climatic conditions as well as the management system.
      Cows in the east and central regions were at a 4.5-fold and 2.0-fold higher risk,
      respectively, of being N. caninum seropositive compared with cows in west region.
      Levels of recent infection were evaluated through an avidity ELISA in
      seropositive animals, being registered a 0.56% and a 1.71% of recent infection in
      beef and dairy cattle respectively (p = 0.006). The results revealed that dairy
      cows had 3.1(95%CI: 1.4; 7.0) higher risk of contracting Neoporosis through
      horizontal transmission than beef cows. A relationship between Brucella abortus
      and N. caninum seroprevalence was also observed. The risk of being N. caninum
      seropositive was two times higher where Brucellosis seroprevalence was >3.5%.
      These results reveal the distribution of N. caninum infection in the cattle
      population in La Pampa, Argentina. 

PMID- 26203997
TI  - PCR identification of five species from the Anopheles maculipennis complex
      (Diptera: Culicidae) in North-Eastern Romania.
AB  - The members of the Anopheles maculipennis complex have been incriminated for the
      transmission of the malaria in Europe, which was endemic until the middle of the
      century. The global warming and the intensification of the intercontinental
      travel constitute a risk of the re-emergence of the malaria in Europe, given the
      presence of the Anopheles vectors. The study has attempted the identification by
      using the PCR (Polymerase Chain Reaction) of the members of the Anopheles
      maculipennis complex from the North-eastern area of Romania from the city of
      Iasi. In total there have been identified by using the PCR amplifying the ITS2
      sequence of the ribosomal DNA, 217 specimens belonging to the complex of A.
      maculipennis among which: 58 A. atroparvus, 18 A. melanoon, 2 A. labranchiae, 52
      A. maculipennis and 87 A. messeae. The ITS2 sequences of the ribosomal DNA have
      been compared to those of the species belonging to the A. maculipennis available
      in GenBank. The Species A. labranchiae is reported for the first time in Romania,
      being identified in the larval stage IV. The adaptation of a new species to the
      climatic conditions present in the North-eastern Romania, confirms the phenomenon
      of global warming and also the intensification of the travelling. As a result of
      the analysis of the A. labranchiae sequence, this one corresponds to the extent
      of 96% to the species from Italy, registered in GenBank, given the fact that a
      high number of the inhabitants of the municipality of Iasi are working in this
      country. 

PMID- 26203998
TI  - Parasitic fauna of a yellow-legged gull colony in the island of Escombreras
      (South-eastern Mediterranean) in close proximity to a landfill site: potential
      effects on cohabiting species.
AB  - We identified the ectoparasites and helminth fauna of yellow-legged gulls (Larus
      michahellis michahellis), breeding near to a solid waste landfill, and compared
      infection levels with those of other yellow-legged gull colonies. Moreover, we
      analysed correlations between parasites and sex and body condition of yellow
      legged gulls, co-infections and the helminth community structure in order to
      propose the role of this species as reservoir of certain parasites. We also
      discuss the potential transmission of parasites between the yellow-legged gull
      and the endangered Audouin's gull, because interactions between these two
      species, such as kleptoparasitism and predation, occur frequently around
      colonies. The following species were recorded: Ornithodorus capensis
      (Arthropoda); Cosmocephalus obvelatus, Paracuaria adunca, Eucoleus contortus,
      Tetrameres skrjabini and Contracaecum sp. (Nematoda); Tetrabothrius cylindraceus
      (Cestoda); Acanthotrema armata, Cardiocephaloides longicollis and
      Ornithobilharzia intermedia (Digenea). Tetrabothrius cylindraceus, A. armata and
      O. capensis are new parasite records for this host. The dependence of yellow
      legged-gulls on fishery discards is supported by the dominance of parasites
      transmitted through marine intermediate hosts with interest to fisheries in the
      study area. However, the shift in diet from natural resources to food derived
      from human activities seems not to affect the parasitic fauna of yellow-legged
      gull. Besides of direct physical contact between individuals in nesting and
      resting habitats, the high availability of fishery discards could increase the
      risk of Audouin's gulls to be infected by common parasites of yellow-legged gull.

PMID- 26203999
TI  - Phyllodistomum spinopapillatum sp. nov. (Digenea: Gorgoderidae), from the Oaxaca
      killifish Profundulus balsanus (Osteichthyes: Profundulidae) in Mexico, with new
      host and locality records of P. inecoli: Morphology, ultrastructure and molecular
      evidence.
AB  - Phyllodistomum spinopapillatum sp. nov. is described from the urinary bladder of
      the Oaxaca killifish, Profundulus balsanus Ahl (Profundulidae) in Rio Pueblo
      Viejo and Rio Santa Cruz, Oaxaca, southwestern Mexico. The new species is
      described based on evidence gathered from morphology, scanning electron
      microscopy (SEM), and partial sequences of the 28S rRNA gene. Diagnostic
      characters of the new species of Phyllodistomum Braun 1899 are the presence of
      spines on the entire body surface and having a ventral sucker almost half the
      size of oral sucker. The new species possess a large number of dome-like papillae
      on the body surface with scattered distribution along the hindbody, and these
      papillae are characteristically spinulated. Phyllodistomum spinopapillatum sp.
      nov. most closely resembles P. inecoli Razo-Mendivil, Perez-Ponce de Leon and
      Rubio- Godoy, 2013, a parasite of the twospot livebearer Pseudoxiphophorus
      bimaculatus (Heckel) from Veracruz, in the Atlantic slope of Mexico. In addition
      to the new species, specimens of P. inecoli were also found parasitising the
      urinary bladder of cyprinodontiforms such as the Mexican molly Poecilia sphenops
      Valencienes in a pond at Santa Maria Coyotepec, and in Profundulus sp. in Rio
      Templo, both in Oaxaca, and in the Porthole livebearer Poeciliopsis gracilis
      (Heckel) in Rio San Juan, as well as in Profundulus punctatus (Gunter) from Rio
      Nueva Francia, both in Chiapas. The distribution and host range of P. inecoli is
      extended to freshwaters of the Pacific slope of Mexico, and to other
      cyprynodontiforms. 

PMID- 26204000
TI  - Diphyllidean cestodes from the bigeye houndshark Iago omanensis (Norman)
      (Carcharhiniformes: Triakidae) in the Gulf of Oman, with the description of
      Coronocestus ehsanentezarii sp. nov. (Echinobothriidae).
AB  - A new species of Coronocestus Caira, Marques, Jensen, Kuchta and Ivanov, 2013 is
      described from Iago omanensis (Norman) from the Gulf of Oman. Coronocestus
      ehsanentezarii sp. nov. differs from C. musteli (Pintner, 1889) Caira, Marques,
      Jensen, Kuchta and Ivanov, 2013 in that its ovary is H- rather than U-shape. The
      new species is easily distinguished from C. diamanti (Ivanov and Lipshitz, 2006)
      Caira, Marques, Jensen, Kuchta and Ivanov, 2013 by the number of spines per
      column on the cephalic peduncle (24-36 vs 95-118). It differs from C.
      hormozganiense (Haseli, Malek, Palm and Ivanov, 2012) Caira, Marques, Jensen,
      Kuchta and Ivanov, 2013 based on a greater number of spines per column on the
      cephalic peduncle (24-36 vs 18-21). The new species differs from C. notoguidoi
      (Ivanov 1997) Caira, Marques, Jensen, Kuchta and Ivanov, 2013 in that of its
      scolex is craspedote rather than acraspedote. Unlike C. coronatum (Robinson 1959)
      Caira, Marques, Jensen, Kuchta and Ivanov, 2013, C. ehsanentezarii sp. nov.
      possesses 29-35 rather than 20 apical hooks in each dorso-ventral group. The new
      species possesses lateral hooklets with two rows (a and b designations) in each
      cluster. This character had been presented earlier only for Andocadoncum Abbott
      and Caira, 2014. Furthermore, a new locality record is presented for C. diamanti
      from Iago omanensis in the Gulf of Oman. Thus, I. omanensis certainly hosts two
      diphyllidean species simultaneously in the Gulf of Oman. The generic diagnosis of
      Coronocestus is also revised to include new data. 

PMID- 26204001
TI  - Detection of high percentage of Trypanosoma cruzi infection, the etiologic agent
      of Chagas disease, in wild populations of Colombian Caribbean triatomines.
AB  - In Colombia it is estimated that about 900,000 persons are infected with T.
      cruzi. There are 25 triatomine species and 5 of them have been reported infected
      with T. cruzi in the Colombian Caribbean region. In order to obtain more
      information about the triatomine populations in this region, 89 wild triatomines
      were collected from four Colombian Departments. The most frequent specie
      collected was Rhodnius pallescens (65%), followed by Rhodnius prolixus (20%),
      Panstrongylus geniculatus (10.1%) and Triatoma dimidiata (1%), found in Bolivar,
      Cordoba, Atlantico/Sucre, and Bolivar Departments, respectively. The majority of
      triatomines (95.5%) were captured in the arboreal ecotope and 76.4% were found
      infected with T. cruzi. Interestingly, some of these triatomine species were
      captured in Departments in which they had not previously been reported and also
      new finding of triatomine species infected with T. cruzi. These results are
      relevant, because they can be consequence of a continued geographical expansion
      of this parasite, not only in the Colombian Caribbean region, but even in all
      Latin America. The information presented here will contribute in the surveillance
      and control strategies of the vectors infected with T. cruzi that circulate in
      four department of Colombian Caribbean region in order to interrupt the
      transmission to human dwelling. 

PMID- 26204002
TI  - Molecular evidence of Theileria equi infection in Hyalomma anatolicum ticks
      infested on sero-positive Indian horses.
AB  - A sizeable Indian equine population is considered to be pre-immune carrier of
      Theileria equi infection. In this study we confirmed the presence of T. equi
      specific DNA in Hyalomma anatolicum ticks which were infested on sero-positive
      horses. Fifty two Indigenous horses were randomly selected from endemic areas and
      their blood and tick samples were collected. Tick salivary glands and blood
      samples were processed for separation of DNA and serum, respectively. Serum
      samples were analyzed by EMA-2ELISA and nine horses were found positive for T.
      equi specific antibodies. Species-specific primers were designed from EMA-2 gene
      of T. equi, so as to amplify 398 bp fragment in PCR. The gene fragment was
      amplified in PCR on the DNA samples (from blood) from these nine sero-positive
      horses. Corresponding six tick's DNA samples collected from these nine
      seropositive animals were observed positive in PCR. Further, qPCR assay
      demonstrated presence of T. equi DNA in infected tick's salivary glands, which
      was also confirmed by microscopic examination of infected acinar. This study
      concluded that Hyalomma anatolicum ticks infested on T. equi seropositive horses
      have sporozoite developmental stage in their salivary glands, which is an
      evidence for transmitting potential of these tick among Indian horse population. 

PMID- 26204003
TI  - Nosema sp. PM-1, a new isolate of microsporidian from infected Papilio machaon
      Linnaeus, based on ultrastructure and molecular identification.
AB  - A new microsporidium, Nosema sp. PM-1, was first isolated from Papilio machaon
      Linnaeus. The spore shape of the PM-1 isolate was a long oval with an average
      size of 3.22 MUm * 1.96 MUm. Ultrastructure observation showed that PM-1 had a
      typical Nosema common diplokaryotic nuclei structure with 10-13 polar filament
      coils, spore wall, plasma membrane, and anchoring disk. The complete rRNA gene
      sequences were obtained by polymerase chain reaction amplification and each rRNA
      unit was arrayed as follows: 5'-LSU (2497 bp)-ITS (179 bp)-SSU (1232 bp)-IGS (278
      bp)-5S (115 bp)-3', which was the same as typical Nosema. The phylogenetic trees
      of rRNA, DNA-directed RNA polymerase II subunit, and tubulin genes all show that
      PM-1 was a sister to the clade comprising Nosema bombycis, Nosema spodopterae,
      and Nosema sp. PX1. The spore morphology, ultrastructure, and complete rRNA
      structure indicate that this isolate assigned to the "true" Nosema group, can
      parasitized in Papilio machaon Linnaeus, which provides a wider host range for
      Nosema. 

PMID- 26204004
TI  - Chitin, a key factor in immune regulation: lesson from infection with fungi and
      chitin bearing parasites.
AB  - The probability of infection with fungi, as well as parasitic nematodes or
      arthropods may increase in overcrowded population of animals and human. The
      widespread overuse of drugs and immunosuppressants for veterinary or medical
      treatment create an opportunity for many pathogenic species. The aim of the
      review is to present the common molecular characteristics of such pathogens as
      fungi and nematodes and other chitin bearing animals, which may both activate and
      downregulate the immune response of the host. Although these pathogens are
      evolutionary distinct and distant, they may provoke similar immune mechanisms.
      The role of chitin in these phenomena will be reviewed, highlighting the immune
      reactions that may be induced in mammals by this natural polymer. 

PMID- 26204005
TI  - The lack of effectiveness of hyperbaric oxygenation as a treatment for Leishmania
      major in a mouse model.
AB  - We aimed to study the effectiveness of hyperbaric oxygen therapy (HOT) (100%
      oxygen at 2 ATA for 70 minutes each session for 20 consecutive days) on BALB/c
      male mice infected with Leishmania major. Fifty-one mice were assigned to six
      groups. Group 1 was treated with HOT from 1 day after the inoculation. In Groups
      2-5, treatment began when the cutaneous lesions appeared. Group 2 received HOT
      only, Group 3 received topical therapy with Leshcutan only, Groups 4 and 5
      received a combination of HOT and Leshcutan for 5 and 10 days respectively, and
      Group 6 did not receive any treatment (control group). When comparing the control
      group with Group 1, treatment with HOT in Group 1 did not significantly affect
      the time of the appearance of the lesions. In contrast, mice treated with
      Leshcutan demonstrated a significant difference in lesion size and spleen
      dimensions as compared to the rest of the mice (p<0.001). The results show that
      HOT treatment has no positive effect on the course of Leishmaniasis in a BALB/c
      mice model infected with Leishmania major. Further studies are needed with a
      mouse model closer to humans and with different HOT protocols. 

PMID- 26204006
TI  - Coccidiosis in European rabbit (Oryctolagus cuniculus algirus) populations in the
      Iberian Peninsula.
AB  - The European rabbit Oryctolagus cuniculus is a keystone species from the Iberian
      Peninsula where viral diseases have played a prominent role in regulating their
      populations. Coccidiosis, a parasitic disease caused primarily by Eimeria spp.,
      is also thought to have important negative effects. However, few studies have
      investigated the impact of coccidia on wild European rabbit populations on the
      Iberian Peninsula. Here we estimate coccidian prevalence in rabbit faecal samples
      collected along transects established in two ecological regions. Six Eimeria
      species, with different pathogenicity, were identified (E. coecicola, E.
      perforans, E media, E. magna, E. irresidua and E. flavescens). Species diversity
      varied significantly between regions although mean oocyst excretion levels were
      generally low in both areas (57.61 s.d.+/-78.07 and 17.03 s.d.+/-27.72, oocyst
      per gram of rabbit faeces). This study is the first to describe the composition
      of the Eimeria spp. assemblage for wild rabbit populations on the Iberian
      Peninsula and provides fundamental information for future studies on the
      potential interaction of viral and parasitic diseases. 

PMID- 26204007
TI  - Angiostrongylus vasorum infection in red foxes (Vulpes vulpes) in southern Italy.
AB  - Angiostrongylus vasorum (Nematoda: Angiostrongylidae) infection was detected at
      post-mortem examination in the pulmonary arteries and hearts of 34/102 (33,3%) of
      red foxes (Vulpes vulpes) from the Campania Region in southern Italy.
      Pathological changes consisted of granulomatous interstitial pneumonia caused by
      larvae and intravascular pulmonary adult nematodes. These changes confirm that
      angiostrongylosis infection in red foxes has a mainly chronic course, in which
      the infected host may disperse parasite larvae in the environment over its
      lifetime. Results suggest that the life cycle of A. vasorum is well established
      in the red fox in the Campania Region representing a potential infection risk for
      dogs. 

PMID- 26204008
TI  - Redescription and phylogenetic relationships of the rare Lyperosomum sarothrurae
      Baer, 1959 (Digenea: Dicrocoeliidae).
AB  - Lyperosomum sarothrurae Baer, 1959 is a rare dicrocoeliid described based on a
      single specimen from Belgian Congo, now Democratic Republic of the Congo, and
      never reported again. The original description lacked several important details
      of the species morphology. This work provides morphological redescription of Lyp.
      sarothrurae based on specimens from Kibale National Park, Uganda which is about
      200 kilometres from the type locality. Results of re-examination of the holotype
      are also provided. Morphology of Lyp. sarothrurae shows some characteristics
      intermediate between those of the species rich genus Lyperosomum Looss, 1899 and
      Megacetabulum Oshmarin, 1964 that includes only 3 species. Due to the lack of
      clear morphological differences between the two genera, Megacetabulum is
      considered here as a junior synonym of Lyperosomum. Molecular phylogenetic
      analysis including Lyp. sarothrurae and all currently available partial sequences
      of the nuclear ribosomal 28S RNA gene of dicrocoeliid species is also included
      and its results are discussed. 

PMID- 26204009
TI  - A new Cosmocercoides species (Nematoda: Cosmocercidae), C. tonkinensis n. sp., in
      the scale-bellied tree lizard (Acanthosaura lepidogaster) from Vietnam.
AB  - A new cosmocercid nematode species, Cosmocercoides tonkinensis n. sp., is
      described from the scale-bellied tree lizard (Acanthosaura lepidogaster) in the
      northern and central parts of Vietnam. The new species is characterized by medium
      sized male worms (4.2-5.1 mm in length and 0.34-0.37 mm in width) relative to
      known members of the genus, with lateral alae, two sharply pointed spicules of
      equal length (0.22-0.26 mm in length), a gubernaculum (0.113-0.122 mm in length),
      16 or 17 pairs of caudal rosettes, and the presence of somatic papillae. Female
      worms are slightly larger than male worms (5.3-5.5 mm in length and 0.32-0.42 mm
      in width), with the vulva situated at 3/5 from the anterior end, and elliptical
      embryonated eggs, 0.064- 0.084 mm long by 0.040-0.048 mm wide. From 19 recorded
      species of the genus, the morphology of C. tonkinensis n. sp. is closest to C.
      multipapillata, C. bufonis, and C. pulcher reported from toads and frogs in East
      Asia. The present new species is differentiated from them by the number of caudal
      rosettes, tail length relative to body length, presence of somatic papillae and
      lateral alae, and embryonated eggs. Furthermore, after C. variabilis in North
      America and C. sauria in Brazil, this new species is only the third species to be
      recorded from a reptilian host. The 18S ribosomal RNA gene (rDNA) of the new
      species is almost identical to that of C. dukae infecting land snails and slugs
      in North America. Between the present new species and C. pulcher from a toad
      (Bufo japonicus) in Japan, remarkably fewer nucleotide changes were noticed in
      the 18S to 28S rDNA including the internal transcribed spacer regions. The
      molecular phylogenetic position of the genus Cosmocercoides is briefly discussed.

PMID- 26204010
TI  - Metazoan parasite infracommunities of Mycteroperca bonaci (Poey, 1960) (Pisces:
      Epinephelidae) in reef and coastal environments off the coast of Yucatan, Mexico.
AB  - The black grouper Mycteroperca bonaci is a commercially important fish off the
      coast of Yucatan, Mexico. To investigate possible differences between parasite
      communities in two different environments, 60 fish were collected from two areas
      during 2010 and 2011 and examined for parasites. The fish were classified into
      two age groups, in each of which the parameters of parasitic infection -
      prevalence, abundance and intensity - were determined. Parasite faunas were
      further described at the infracommunity level. Using both univariate (PERMANOVA)
      and multivariate statistical methods, the values of richness, abundance,
      diversity and Brillouin evenness as well as the Index values of Bray-Curtis and
      Jaccard for similarity were calculated and compared. The results of these tests
      and of CAP discriminant analyses at the two sites showed the existence of two
      distinct parasite communities. The parasite taxa mainly responsible for the
      differences were the digeneans Dollfustrema sp., Prosorhynchus spp.,
      Lepidapedoides epinepheli and Hamacreadium mutabile, and the nematode Philometra
      salgadoi. The potential for some of these parasites to be used as biological tags
      for stock identification of M. bonaci is discussed. 

PMID- 26204011
TI  - Effect of body size on the abundance of ectoparasitic mites on the wild rodent
      Oligoryzomys nigripes.
AB  - The abundance of parasites on a host can be affected by several factors; in this
      study, we investigated the influence of sex and body size of the host rodent
      Oligoryzomys nigripes on the abundance of ectoparasitic mites (Acari:
      Mesostigmata). The generalized linear model indicated that body size (indicative
      of age) of the host rodent O. nigripes significantly contributed to the variation
      in the abundance of mites on host rodents at the Experimental Station of
      Itirapina. This trend of increased parasitism on hosts with larger body sizes may
      be linked to the fact that larger individuals are able to support the coexistence
      of a larger number of parasites, and being more mobile, are more exposed to
      infection by parasites. 

PMID- 26204012
TI  - Fatal Paratanaisia bragai (Digenea: Eucotylidae) infection in scarlet macaws (Ara
      macao) in Costa Rica.
AB  - We report on four fatal cases of renal infection due to Paratanaisia bragai in
      scarlet macaws (Ara macao) from two rescue centres in Costa Rica. At necropsy,
      birds had severe dehydration and cachexia. Two birds had hydropericardium,
      oedematous lungs, and liver lipidic degeneration. All birds had enlarged kidneys
      with brown pale discoloration and diffuse white spots on the cortical and sliced
      surfaces. Ureters were filled with many specimens of P. bragai.
      Histopathologically, the urinary system revealed multifocal interstitial
      lymphocytic-plasmacytic nephritis, multifocal mineralization of renal tubules,
      and interstitial fibrosis associated with flukes. Death of all scarlet macaws was
      related to severe nephritis leading to chronic renal failure due to P. bragai
      infection. It is plausible that P. bragai infection of scarlet macaws was
      accidental due to ingestion of the gastropod intermediate host inside the cages
      during the rainy season when humidity is higher and gastropods are more active.
      This represents the second report of parasitism by Eucotylidae digeneans in birds
      of Psittaciformes and the first in scarlet macaws. 

PMID- 26204013
TI  - Molecular characterization of muscle-parasitizing didymozoid from a chub
      mackerel, Scomber japonicus.
AB  - Didymozoids found in the muscles of marine fish are almost always damaged because
      they are usually found after being sliced. Therefore, identifying muscle
      parasitizing didymozoids is difficult because of the difficulty in collecting non
      damaged worms and observing their organs as key points for morphological
      identification. Moreover, muscle-parasitizing didymozoids are not easily found
      because they parasitize at the trunk muscles. Therefore, muscle-parasitizing
      didymozoid classification has not progressed because there are few opportunities
      to detect them. Our recent report was the first to describe the usefulness of
      sequencing analysis for discrimination among muscle-parasitizing didymozoids.
      Recently, we found a didymozoid in the trunk muscle of a chub mackerel Scomber
      japonicus. The present study genetically compares the present isolate with other
      muscle-parasitizing didymozoids. The present isolate differs markedly from the
      previously unidentified didymozoid from an Atlantic mackerel S. scombrus by
      phylogenetic analysis of 18S rDNA. It also differs from other muscle-parasitizing
      didymozoids from other host species based on phylogenetic analyses of 18S, 28S
      rDNAs, and coxI loci. These results suggest that sequencing analysis is useful
      for the discrimination of muscle-parasitizing didymozoids. Combining the present
      data with earlier data for sequencing analysis, muscle-parasitizing didymozoids
      from seven marine fish species were classified as seven species. We proposed
      appellations for six distinct muscle-parasitizing didymozoids for future
      analysis: sweetlips fish type from Diagramma pictum and Plectorhinchus cinctus,
      red sea bream type from Pagrus major, flying fish type from Cypselurus heterurus,
      Atlantic mackerel type from Scomber scombrus, chub mackerel type from S.
      japonicus, and purple rockcod type from Epinephelus cyanopodus. 

PMID- 26204014
TI  - The use of phytotherapy in diseases caused by parasitic protozoa.
AB  - The paper presents an overview of the use of natural therapeutic agents in
      combating parasitic diseases. Nowadays there is increasing demand for proven
      plant therapies, which often are found to be more effective than synthetic
      pharmaceuticals in chronic diseases. In many cases herbal preparations perfectly
      supplement the conventional treatment and at the same time do not cause side
      effects. On the pharmaceutical market there are many drugs of plant origin which
      have been applied in the treatment of parasitic diseases. However, researchers
      are still looking for new plants, or specific substances isolated from them,
      which can be used in therapy. In this paper, drugs of plant origin used in the
      treatment of amoebiasis, giardiasis, malaria, leishmaniasis, trypanosomiasis and
      acanthamoebiasis are described. 

PMID- 26204015
TI  - Parasite communities of the elongate tigerfish Hydrocynus forskahlii (Cuvier
      1819) and redbelly tilapia Tilapia zillii (Gervais 1848) from Lake Turkana,
      Kenya: influence of host sex and size.
AB  - Fish is an important food source for an estimated 300,000 people inhabiting the
      shores of Lake Turkana, Kenya. Despite its large size (7560 km2) and importance,
      the lake remains one of the least studied in the Great Lakes Region of Africa.
      This study describes the parasite community of the elongate tigerfish Hydrocynus
      forskahlii (Cuvier, 1819) and the redbelly tilapia Tilapia zillii (Gervais,
      1848). A total of 87 individuals (43 H. forskahlii and 44 T. zillii) were
      dissected and examined for parasites. Two taxa infected H. forskahlii, the
      dominant one being an anisakid nematode Contracaecum sp. (L3) (P = 83.7%, mean
      intensity (MI) = 46.0, abundance (A) = 38.5). Twelve parasite taxa were recovered
      from T. zillii, with metacestodes of the gryporhynchid cestode Amirthalingamia
      macracantha being dominant (P = 79.5, MI = 10.3, A = 8.2). This was the first
      report of a mixture of merocercoids and plerocercoids in the same host. Fish size
      was positively correlated with the major parasite infection levels, but, the
      prevalence of Contracaecum sp. in H. forskahlii was negatively correlated with
      size, probably reflecting ontogenetic shifts in habitats and diets with age. Fish
      sex was not a significant influencing factor, with the exception of Contracaecum
      sp. in H. forskahlii, where prevalence differed significantly between sexes
      (p<0.05), with the females having a higher prevalence than the males. We conclude
      that H. forskahlii had a poor parasitic community but that the infection levels
      with Contracaecum sp. were high. T. zillii had a rich parasite fauna, although,
      most parasites occurred at low intensities. 

PMID- 26204016
TI  - Molecular detection of Dirofilaria immitis, Hepatozoon canis, Babesia spp.,
      Anaplasma platys and Ehrlichia canis in dogs on Costa Rica.
AB  - Although vector-borne diseases are important causes of morbidity and mortality in
      dogs in tropical areas, there is little information on these conditions in Costa
      Rica. In PCRs of blood from dogs in Costa Rica, we did not detect DNAs of
      Rickettsia (R.) felis and Coxiella (C.) burnetii but we did find evidence of
      infection with Dirofilaria (D.) immitis (9/40, 22.5%), Hepatozoon (H.) canis
      (15/40, 37.5%), Babesia spp. (10/40, 25%; 2 with B. gibsoni and 8 with B.
      vogeli), Anaplasma (A.) platys (3/40, 7.5%) and Ehrlichia (E.) canis (20/40,
      50%). Nine dogs (22.5%) were free of any vector-borne pathogens while 14 (35%)
      were infected with a single pathogen, 11 (27.5%) with two, 4 (10%) with three, 1
      (2.5%) with four, and 1 (2.5%) with five pathogens. Dogs in Costa Rica are
      commonly infected with vector-borne agents. 

PMID- 26204017
TI  - Predominance of Cryptosporidium parvum genotype among diarrheic children from
      Egypt as an indicator for zoonotic transmission.
AB  - Cryptosporidium is a genus of zoonotic pathogens transmissible from a variety of
      animals to humans and is a considerable public health concern. It is a
      significant cause of diarrheal disease in developing and industrialized nations.
      Cryptosporidium parvum and Cryptosporidium hominis are the main agents of
      cryptosporidiosis in humans. In this study we identified the genotypes of the
      Cryptosporidium isolates from clinical samples from diarrheic children using
      polymerase chain reaction (PCR) amplification and restriction fragment length
      polymorphism (RFLP) analyses of the TRAP-C2 gene (Thrompodin Related Adhesive
      Protein). A total of 430 fecal specimens from 1 to 14 years children were
      collected from inpatient and outpatient clinics of Benha University, Educational
      and Children Specialized Hospitals, Benha, Qalubyia, and were microscopically
      examined for Cryptosporidium spp. All infected samples were also analyzed using
      nested PCR. A polymerase chain reaction (PCR)-restriction fragment length
      polymorphism (RFLP) analysis of the (266-366 bp) of TRAP-C2 gene was also used to
      detect and identify Cryptosporidium spp. in PCR- positive samples. The results
      showed that 50 (11.63%) of the specimens were positive for Cryptosporidium spp.
      Genomic amplification and restriction digestion of the PCR products by BstETI,
      Hae III for TRAP-C2 gene restriction enzymes revealed that 82% (41/50) had C.
      parvum, 12% (6/50) had C. hominis, and three (3/50) samples (6%) had mixed
      infections. In conclusion, elevated prevalence of C. parvum, suggesting animal
      human (zoonotic) transmission and further investigations are required to
      determine the subgenotypes of C. parvum to clarify the mode of transmission in
      order to improve the control measures. 

PMID- 26204018
TI  - Wild boar density drives Metastrongylus infection in earthworm.
AB  - Larvae of Metastrongylus spp. lungworms infect wild boar (Sus scrofa) definitive
      hosts through earthworms (Lumbricidae). We compared the abundance and
      Metastrongylus spp. larval infection measures of earthworms between two areas
      (both in Zselic, Hungary, 2012) characterized by markedly different wild boar
      population densities. Estimated wild boar density was 0.03 animal/ha in free
      range area and 1.03 animal/ha in enclosure. The mean abundance of earthworm
      populations (mostly Allolobophora, Aporrectodea, and Lumbricus spp.) was assessed
      by analysing 140-140 soil samples. The assesment of Metastrongylus spp. larval
      infection measures was based on cca 100-100 earthworms derived from the two
      areas. The abundance of earthworms and their Metastrongylus spp. larval infection
      measures (prevalence and mean intensity) were significantly lower in the free
      range than in the enclosure. Furthermore, using a finer scale within the
      enclosure, we compared wild boar feeding sites (n = 30) to other sites (n = 75).
      Earthworm populations were significantly more abundant and carried significantly
      more prevalent and more abundant larval lungworm infections at the former sites.
      These results suggest that high wild boar density and forage supplementation in
      enclosures increase both the abundance and the larval Metastrongylus infections
      of earthworms. 

PMID- 26204019
TI  - The effect of trematode parthenites on the individual fecundity of Bithynia
      troscheli (Prosobranchia: Bithyniidae).
AB  - We studied the long-term infection of Bithynia troscheli (Paasch, 1842) snails
      with trematodes and estimated the influence of trematode parthenites on the
      individual fecundity of female snails from the Kargat River (Chany Lake, Russia).
      The prevalence of B. troscheli females infected by trematode parthenites varied
      from 7.12% to 17.35% in different years. Eleven redioid species from 5 families
      and 9 sporocystoid species from 5 families of trematodes were found during this
      investigation. Snails' fecundity was analysed in relation to the type of
      infection (redioid or sporocystoid species). Fecund females of B. troscheli were
      uninfected or they had pre-patent infections from 5 families of trematodes
      (Psilostomidae, Notocotylidae, Prosthogonimidae, Lecithodendriidae, and
      Cyathocotylidae). 89.9% of infected B. troscheli females were infertile.
      Moreover, 13.57% and 1.29% egg capsules (of infected and uninfected females,
      respectively) were without embryos (chi2 = 323.24, p<0.001). The results of the
      two-way analysis of variability confirmed that trematode parthenites influenced
      significantly the individual fecundity of B. troscheli. The age of B. troscheli
      females alone did not alter the individual fecundity, however age in combination
      with infection by tremathode parthenites influenced significantly the number of
      normal egg capsules. We also found that under unfavorable environmental
      conditions the proportion of fertile females increased by 23.7% among uninfected
      and by 219% among infected females.

PMID- 26204020
TI  - Serological screening of selected microsporidia in HPV-positive women.
AB  - Microsporidiosis is considered to be emerging opportunistic infection in
      immunocompromised individuals worldwide. The aim of this study was to identify
      the specific serum antibodies to intestinal microsporidia Encephalitozoon
      cuniculi and Encephalitozoon intestinalis in women with Human Papillomavirus HPV
      and without HPV by the indirect immunofluorescence (IFA). From total number of
      669 examined women, 225 were HPV positive and 444 women HPV negative. Overall the
      study comprised of 10.8% women with positive result for presence of E. cuniculi
      antibodies. In group 1 (HPV-positive women) it was more than 28% and in group 2
      (HPV-negative women) it was less than 2% (p<0.001). E. intestinalis infection was
      found in total of 4.48% women, in group 1 it was present in less than 6% and in
      group 2 in less than 4% of women. 

PMID- 26204021
TI  - Cloning and expression of apyrase gene from Ancylostoma caninum in Escherechia
      coli.
AB  - Apyrase encoding metal-ions activated plasma membrane protease is present in
      animal and plant tissues. This enzyme can hydrolyze ADP and ATP pyrophosphate
      bond, resulting in AMP and free phosphate groups, and plays an important role for
      insects and parasites to evade host immune system. However localization and
      function of apyrase in the canine hookworm, Ancylostoma caninum, remains unknown.
      To analyze apyrase gene in A. caninum (a eukaryotic parasitic hookworm), a pair
      of primers was designed according to the previous EST data. The full-length cDNA
      of apyrase gene was amplified from A. caninum by RT-PCR. The partial cDNA of
      apyrase encodes 249 amino acid protein was expressed in Escherechia coli. The
      recombinant protein was induced to express under proper conditions and the
      molecular size was as expected. The recombinant protein was purified. The
      transcripts of apyrase in different stages of A. caninum were analyzed by the
      Real-time PCR assay, and Immuno-localization assays were used to research the
      protein expression in different stages of A. caninum. 

PMID- 26204022
TI  - Biological and molecular characterization of a Trypanosoma cruzi isolate obtained
      from Panstrongylus megistus captured in Sao Paulo State, Brazil.
AB  - An isolate of Trypanosoma cruzi obtained from P. megistus captured in the
      peridomicile area of a home in Santo Antonio do Jardim city in the State of Sao
      Paulo, denominated T. cruzi Mogi, was characterized biologically and molecularly.
      The RFLP analysis of the D7 divergent domain in the 24Salpha rDNA and of the mini
      exon positioned the T. cruzi isolate within the TcI group. Phylogenetic analysis
      performed with the trypanosomatid barcode confirmed that the isolate belongs to
      the TcI group, with high homology to the 3014 c1 T.cruzi strain. The biological
      characterization of the isolate in rats showed a prepatent period of about 8
      days, low parasitemia and tropism for cardiac, skeletal and colonic muscles. In
      Swiss mice the T. cruzi Mogi isolate showed a prepatent period of about 22 days,
      intermittent parasitemia in some animals, and tropism for cardiac and colonic
      muscles. Despite the inherent difficulty of identifying correlations amongst the
      molecular and biological characteristics of different T. cruzi groups, the
      tropism for colonic muscle demonstrated by T. cruzi Mogi represented a
      peculiarity of this isolate within the TcI group. 

PMID- 26204023
TI  - A new Gyrodactylus strain on brown trout (Salmo trutta) in Janisjarvi, Russian
      Karelia, and a literature revision of salmonid parasites of the genus
      Gyrodactylus in North-Western Russia and adjacent areas.
AB  - A Gyrodactylus parasite infected juveniles of brown trout (Salmo trutta L.) in a
      hatchery in Lake Janisjarvi, Russian Karelia. Molecular identification by ITS1
      5.8S-ITS2 of ribosomal DNA indicated that the infection was caused by a non
      segregating hybrid clone between unknown Gyrodactylus species and Gyrodactylus
      teuchis Lautraite, Blanc, Thiery, Daniel & Vigneulle, 1999, described from brown
      trout collected in France. The mitochondrial CO1 was sequenced from the hybrid,
      but it is not available from pure G. teuchis from type locality. The
      mitochondrial DNA was an independent clade among the wageneri group parasites,
      differing from the nearest relative G. derjavinoides by 19%. Morphometric
      measurements of the Janisjarvi parasite were compared with separate (host
      specific) G. salaris strains from farmed rainbow trout and salmon in Lake Onega,
      and with available data on G. teuchis from Western Europe, Austria and Poland.
      All isolates were distinguishable by morphometry, and the measurements are a
      useful primary diagnostic tool for the salmonid parasites in Karelian great lakes
      and fish farms. Pure G. teuchis is not found on Russian territory, and the other
      parent of the hybrid has not been discovered yet in any other country. A mini
      review of Gyrodactylus on salmonids in the Russian Karelia is presented. 

PMID- 26204024
TI  - Phylogeography analysis and molecular evolution patterns of the nematode parasite
      Heligmosomum mixtum based on mitochondrial DNA sequences.
AB  - Mitochondrial DNA was explored to study phylogeography of the nematode parasite
      Heligmosomum mixtum and elucidate molecular evolution pattern of cytochrome b
      gene. The size of cyt b gene ranged from 511 bp to 591 bp and the average of GC
      contents was 28.9%. The overall transition/transversion ratio R was 5.773
      indicating that the transitions are more frequent than transversion. The aligned
      sequences allowed identifying 54 mtDNA haplotypes among the 119 examined
      individuals. The genetic divergence registered among the populations of H. mixtum
      was low (0.3% to 1.5%). Neighbor-joining and maximum Likelihood trees evidenced a
      huge polytomy and unstructured phylogeographic pattern among the studied
      populations. The demographic analyses tend to evidence a recent and rapid
      expansion of H. mixtum. Our results imply a positive selection and the genetic
      hitchhiking effect is unlikely. Parameters performed supported scenario of sweep
      selection and recent expansion of H.mixtum populations. Both positive selection
      and demographic histories have jointly contributed to the observed patterns of
      nucleotide diversity and haplotypes structure. The comparison of the
      phylogeographical pattern of H. mixtum with the one of its most common rodent
      host M. glareolus, confirmed a strong incongruence between the two species. These
      results strongly suggest that the parasite would not be specific to M. glareolus
      and that it would switch easily from one rodent species to another. The
      mitochondrial diversity seems to be unstructured with any biogeographic
      repartition of the variability and that the genetic structure of H. mixtum is
      probably associated with weak host specificity. 

PMID- 26204026
TI  - The in vitro antimalarial interaction of 9-hydroxycalabaxanthone and alpha
      mangostin with mefloquine/artesunate.
AB  - Multidrug resistance Plasmodium falciparum is the major health problem in
      Thailand. Discovery and development of new antimalarial drugs with novel modes of
      action is urgently required. The aim of the present study was to investigate the
      antimalarial interaction of 9-hydroxycalabaxanthone and alpha-mangostin with the
      standard antimalarial drugs mefloquine and artesunate in chloroquine sensitive
      (3D7) and chloroquine resistant (K1) P. falciparum clones in vitro. Median
      (range) IC50 (drug concentration which produces 50% parasite growth inhibition)
      values of the 9-hydroxycalabaxanthone, alpha-mangostin, artesunate and mefloquine
      for 3D7 vs K1 clones were 1.5 (0.9-2.1) vs 1.2 (1.1-1.6) MUM, 17.9 (15.7.0-20.0)
      vs 9.7 (6.0-14.0) MUM, 1.0 (0.4-3.0) vs 1.7 (1.0-2.5) nM, and 13.3 (11.1-13.3) vs
      7.1 (6.7-12.2) nM, respectively. Analysis of isobologram and combination index
      (CI) of 9-hydroxycalabaxanthone with artesunate or mefloquine showed synergistic
      and indifference antimalarial interaction, respectively. alpha-mangostin
      artesunate combination exhibited a slight antagonistic effect of antimalarial
      interaction, whereas alpha-mangostin and mefloquine combination showed
      indifference interaction in both clones. The combination of 9
      hydroxycalabaxanthone with alpha-mangostin showed the synergistic antimalarial
      interaction in both clones. 

PMID- 26204025
TI  - Risk of human toxocarosis in Poland due to Toxocara infection of dogs and cats.
AB  - The purpose of this paper was to present the current data on the risk of
      toxocarosis in humans in Poland and to give an overview of the clinical and
      diagnostic aspects of the disease. The number of reported clinical cases of
      Toxocara infection in children in Poland in medical literature has increased
      recently. The results of field surveys aimed to evaluate the soil contamination
      with geohelminth eggs conducted during the last few years showed that Toxocara is
      the most common zoonotic agent in urban public sites and in rural settlements.
      The questionnaire revealed rural inhabitants' low awareness of zoonotic parasite
      threats to humans. In particular parents should be advised as to what proper
      preventive measures to undertake to eliminate the toxocarosis risk factors for
      children in rural environment. Prevention of initial environment contamination
      with Toxocara canis and T. cati eggs, which includes proper treatment regimes to
      eliminate patent infections in dogs and cats and preventing pets from defecating
      in public areas and private households is vital. To provide the public with
      suitably presented information as well as pet owners with uniform
      recommendations, a close collaboration between veterinary and public health
      professionals is crucial. 

PMID- 26204027
TI  - New species of Oswaldofilaria (Nematoda; Filarioidea; Onchocercidae) and other
      helminths in Acanthosaura cardamomensis (Sauria; Agamidae) from Indochina
      Peninsula.
AB  - Oswaldofilaria acanthosauri sp. nov. from the body cavity of the Cardamom
      Mountain horned agamid, Acanthosaura cardamomensis (Sauria: Agamidae), collected
      in Pursat Province, Cambodia is described. Of the 14 species assigned to
      Oswaldofilaria, O. acanthosauri sp. nov. is most similar to those species with
      spicular ratio of less than 2, namely, O. brevicaudata and O. chlamydosauri.
      Oswaldofilaria acanthosauri sp. nov. is easily separated from these 2 species in
      that O. brevicaudata is a South American species and in O. chlamydosauri the
      distal ends of the spicules are pointed not blunt. Mature individuals of 2
      additional species of Nematoda, Meteterakis singaporensis and Orneoascaris
      sandoshami, as well as larvae assignable to Ascariidae were found. Acanthosaura
      cardamomensis represents a new host record for Meteterakis singaporensis,
      Orneoascaris sandoshami and Ascariidae (larvae). 

PMID- 26204028
TI  - The pathogenic role of Blastocystis isolated from patients with irritable bowel
      syndrome and colitis from Iasi, Romania.
AB  - Blastocystis is a common parasite and regarded as one of the etiologic agents of
      irritable bowel syndrome, colitis and chronic diarrhea. Our study was undertaken
      in order to identify different subtypes of Blastocystis isolated in patients with
      irritable bowel syndrome and colitis, as well as with chronic diarrhea and to
      evaluate their pathogenic potential. Seventy-three subjects (10 asymptomatic
      infected subjects, 49 subjects harboring Blastocystis or associated with other
      etiologic agents like bacteria, yeasts, protozoa, helminthes and 14 subjects with
      unknown etiologic agents) were investigated by in vitro parasitological and
      bacteriological stool samples followed by PCR subtyping of Blastocystis using STS
      primers, immunological markers (total serum IgA and IgE antibody levels),
      Helicobacter pylori antigen rapid test and fecal occult blood test. Also, among
      49 subjects, there were 12 subjects harboring Blastocystis as the single
      etiologic agent. Subtyping proved that only three subtypes of Blastocystis were
      identified as following: subtype II (66.66%) in single infected subjects, subtype
      I (16.66%) in mixed infection with subtype II and subtype IV (8.33%) in single
      infected subjects. Total serum IgA and IgE antibody levels were in normal range.
      Subtype II was the most frequent subtype followed by subtype I and subtype IV of
      Blastocystis isolates in patients with irritable bowel syndrome, colitis, and
      chronic diarrhea as well as in asymptomatic infected group. Our results suggest
      that the severity of clinical manifestations depend on factors involving the host
      and possible parasitic density and not necessarily by isolated subtype. 

PMID- 26204029
TI  - Population dynamic of two digenean species parasitizing the grass shrimp
      Palaemonetes argentinus Nobili 1901 (Decapoda: Palaemonidae) in a lentic
      environment from Argentina.
AB  - The microphallids Microphallus szidati and Levinseniella cruzi parasitized at
      least three crustacean species as second intermediate host in Mar Chiquita
      coastal lagoon: the crabs Neohelice granulata and Cyrtograpsus angulatus and the
      grass shrimp Palaemonetes argentinus. Palaemonetes argentinus acts as host for
      both metacercariae in brackish and freshwater environments; however the seasonal
      variations of these digeneans in freshwater habitats remain unexplored. The aim
      of the present study was to analyze the seasonal dynamic of the larval digenean
      populations parasitizing P. argentinus in a lentic environment. From the total
      sample of 600 P. argentinus collected seasonally, 28.370 and 194 metacercariae of
      M. szidati and L. cruzi, respectively, were recovered. Microphallus szidati was
      characterized by high prevalence, 100% in all seasons. In contrast, L. cruzi
      presented low prevalence values, which increased towards summer. The two species
      of digeneans exhibit seasonal fluctuations in intensity of infection, which was
      related to host size. Temporal variation of larval digenean assemblage in the
      crustacean host is probably associated with the presence of the other hosts
      included in their life cycles. The high values of prevalence found for M. szidati
      in Nahuel Ruca lagoon suggest that P. argentinus could favor the contact between
      the larval digenean and the definitive hosts, establishing the presence of M.
      szidati also in freshwater environments and, thus, increasing the presence of the
      parasite in different areas of Mar Chiquita coastal lagoon. 

PMID- 26204030
TI  - Two new Dactylogyrus species (Monogenea: Dactylogyridae) D. angorae and D.
      turcicus from Capoeta angorae and C. mauricii endemic fishes in Turkey.
AB  - Two new Dactylogyrus spp., D. angorae and D. turcicus have been described from
      the gills of the endemic cyprinid fishes, Capoeta angorae and C. mauricii from
      the Anatolian Region of Turkey. The shape of the anchors, hooks and the
      copulation organ of both species differ from those of the Dactylogyrus spp. found
      on other Capoeta species known from the Ponto-Caspian and Tigris-Euphrates
      regions. 

PMID- 26204031
TI  - First record of Toxoplasma gondii in Chaetophractus villosus in Argentina.
AB  - Toxoplasma gondii is an obligate intracellular apicomplexan parasite that causes
      abortion and reproductive disorder in domestic animals. T. gondii is a common
      worldwide disease in homeothermic animals, including birds and humans. The aim of
      the present study was to determine the presence of antibodies against T. gondii
      in the armadillo Chaetophractus villosus in the province of La Pampa, Argentina.
      Serum samples were collected from 150 individuals (70 males and 80 females). For
      serological detection of T. gondii, a latex agglutination test was first
      performed and then positive sera were confirmed with an indirect hemagglutination
      test, using 1:4 to 1:64 dilutions. Results showed that 27% (41) of the samples
      presented titers for antibodies against T. gondii. There were not significant
      differences between the presence of antibodies against T. gondii and age or sexes
      of the armadillos. Results show that presence of T. gondii antibodies in
      armadillos were associated with presence of pigs, and sheep, however there was
      not association with chickens and dairy cattle in capture site. T. gondii has an
      important presence in C. villosus population, suggesting a potential zoonotic
      risk for humans and wildlife animals when C. villosus meats are consumed raw or
      undercooked. This is the first record of the presence of antibodies against T.
      gondii in C. villosus. 

PMID- 26204032
TI  - New morphological data and first description of gravid female of Cucullanus bagre
      Petter, 1974 (Seuratoidea: Cucullanidae) from Bagre bagre (Linnaeus, 1766)
      (Siluriformes: Ariidae) off Brazil.
AB  - Cucullanus bagre Petter, 1974 (Cucullanidae) is redescribed based on the
      examination of newly collected material and the revaluation of type specimens,
      using light and for the first time scanning electron microscopy. Parasite
      specimens were collected from the intestine of the coco sea catfish Bagre bagre
      (Linnaeus) (Ariidae) off the South Atlantic coast, State of Rio de Janeiro,
      Brazil. Detailed morphological analysis revealed the presence of an unpaired
      papilla just anterior to the cloacal protrusion in male, that was overlooked in
      the original description. Descriptions of the adult female and eggs are provided
      for the first time; these gravid specimens have the general morphometry quite
      similar to that of juveniles. Additionally, detailed description and illustration
      of sclerotized plates present on the oesophastome is provided. The far posterior
      location of the excretory pore with thick-walled excretory duct, the conspicuous
      protrusions present on both anal and cloacal regions and the number and
      arrangement of caudal papillae in males are considered to be important diagnostic
      features for C. bagre. All the specimens from type material were together in one
      vial and not separated in two vials as stated in the original description, making
      it impossible to determine which is the holotype, allotype or paratypes. This is
      the first report of C. bagre in Brazil, which expands its geographical
      distribution to South Atlantic waters. 

PMID- 26204033
TI  - Further studies on Toxascaris leonina (Linstow, 1902) (Ascaridida: Ascarididae)
      from Felis lynx (Linnaeus) and Panthera leo (Linnaeus) (Carnivora: Felidae).
AB  - Toxascaris leonina (Linstow, 1902) is a most common intestinal parasite of
      various animals in Felidae and Canidae. In the present paper, light and scanning
      electron microscopy (SEM) were used to study the morphological aspects of adult
      worms of this nematode in detail, based on the material collected from Panthera
      leo (Linnaeus) and Felis lynx (Linnaeus) (Carnivora: Felidae) in China. The
      results showed that there were some morphometric differences between the present
      material and the previous studies, including the body size, the width and length
      of cervical alae, the number of denticles on each lip and the tail length of the
      female. Previously unreported morphological features were also revealed. These
      supplementary morphological and morphometric data contributed to a more accurate
      identification of this worldwide distributed ascarid nematode. 

PMID- 26204034
TI  - Parasitism underground: lice (Insecta: Phthiraptera) from Ctenomys talarum
      (Rodentia: Ctenomyidae) along its coastal distribution in Argentina.
AB  - Species of South American subterranean rodents belonging to the genus Ctenomys
      (commonly called tuco-tucos) are widely distributed across the southern
      Neotropical region. Despite their relatively well-studied biology and
      reproductive physiology, current knowledge of their ectoparasite fauna is limited
      to a few ambiguous studies, based on scattered samples from a small number of
      host individuals. Ctenomys talarum is the most widely distributed species in the
      genus. Lice (Phthiraptera) were collected from these tuco-tucos throughout their
      entire coastal range. Two species, one chewing louse (Gyropus parvus), and one
      sucking louse (Eulinognathus americanus) were collected. The distribution ranges
      for both louse species were extended with new locality records. No lice were
      found in two host populations. Furthermore, co-occurrence of both ectoparasites
      was not detected. 

PMID- 26204035
TI  - Buxtonellosis and coccidiosis of cattles in Northern Serbia.
AB  - The study presents the results of a two-year research of protozoan infections of
      cattles from the Northern-Backa district (Vojvodina, Serbia). The research was
      conducted on cow-farms and in private cattle-breeding households, with variuos
      levels of hygenie. The study included 224 specimens (71 calves, 48 hifers and 105
      cows). 22.91% of examined heifers and 15.23% of cows were infected with the
      ciliate Buxtonella sulcata. The presence of coccidiosis was detected in 45.07% of
      the calves, 14.58% of the heifers and 6.67% of the cows. The clinical signs of
      diarrhoea were established in all of the specimens which had more than 1,500
      cysts of B.sulcata in 1g of faeces. In the examined calves the number of oocysts
      was less than 1500 in 1g of faeces, so the coccidiosis did not influence the
      incidence of the diarrhoea. The results show the first diagnostic record of the
      ciliate B.sulcata of bovines in Serbia, and this finding contributes to the
      existing knowledge about the etiopathogenesis of protozoan disease of cattle in
      this area. 

PMID- 26204036
TI  - Effect of structurally related flavonoids from Zuccagnia punctata Cav. on
      Caenorhabditis elegans.
AB  - Zuccagnia punctata Cav. (Fabaceae), commonly called jarilla macho or pus-pus, is
      being used in traditional medicine as an antiseptic, anti-inflammatory and to
      relieve muscle and bone pain. The aim of this work was to study the anthelmintic
      effects of three structurally related flavonoids present in aerial parts of Z.
      punctata Cav. The biological activity of the flavonoids 7-hydroxyflavanone (HF),
      3,7-dihydroxyflavone (DHF) and 2',4'-dihydroxychalcone (DHC) was examined in the
      free-living nematode Caenorhabditis elegans. Our results showed that among the
      assayed flavonoids, only DHC showed an anthelmintic effect and alteration of egg
      hatching and larval development processes in C. elegans. DHC was able to kill 50%
      of adult nematodes at a concentration of 17 MUg/mL. The effect on larval
      development was observed after 48 h in the presence of 25 and 50 MUg/mL DHC,
      where 33.4 and 73.4% of nematodes remained in the L3 stage or younger. New
      therapeutic drugs with good efficacy against drug-resistant nematodes are
      urgently needed. Therefore, DHC, a natural compound present in Z. punctata, is
      proposed as a potential anthelmintic drug. 

PMID- 26204037
TI  - Coccidia in passerines from the Nevado de Toluca National Park, Mexico.
AB  - In this study, we found unsporulated coccidia oocysts in passerines from the
      Nevado de Toluca National Park, Mexico. We captured birds and took samples of
      their droppings during three field visits. We examined a total of 72 fecal
      samples and found unsporulated coccidia oocysts in 10 samples from five passerine
      species: Atlapetes pileatus (3), Cardelina ruber (1), Mniotilta varia (1),
      Oreothlypis celata (2) and Regulus calendula (3). This appears to be the first
      recorded study of unsporulated coccidia oocysts in passerine species from Mexico.

PMID- 26204038
TI  - Case Report of dirofilariasis in grey wolf in Serbia.
AB  - This paper describes a case of dirofilariasis in a two-year old, female grey wolf
      (Canis lupus lupus). The autopsy revealed the presence of 42 adult forms of
      Dirofilaria immitis in the pulmonary artery, right ventricle and right atrium,
      varying in length from 9.5 to 30 cm. This is, to the best of our knowledge, the
      second report of D. immitis in grey wolves in Serbia. Our finding confirms that
      the wolf, as a subspecies distinct from the dog, should also be considered as a
      very suitable definitive host for dirofilariasis. 

PMID- 26204039
TI  - Aptensio XR--another long-acting methylphenidate.

PMID- 26204040
TI  - Prestalia--another combination for hypertension.

PMID- 26204041
TI  - Namzaric--a combination of 2 old drugs for Alzheimer's disease.

PMID- 26204042
TI  - Hip Strength Testing of Soccer Players With Long-Standing Hip and Groin Pain:
      What are the Clinical Implications of Pain During Testing?
AB  - OBJECTIVE: To investigate whether self-reported pain during hip strength testing
      correlates to a large degree with hip muscle strength in soccer players with long
      standing unilateral hip and groin pain. DESIGN: Cross-sectional study. SETTING:
      Clinical assessments at Sports Orthopaedic Research Center-Copenhagen (SORC-C),
      Arthroscopic Centre Amager, Copenhagen University Hospital, Denmark.
      PARTICIPANTS: Twenty-four male soccer players with unilateral long-standing hip
      and groin pain. INTERVENTIONS: The soccer players performed 5 reliable hip muscle
      strength tests (isometric hip flexion, adduction, abduction, isometric hip
      flexion-modified Thomas test, and eccentric hip adduction). MAIN OUTCOME
      MEASURES: Muscle strength was measured with a hand-held dynamometer, and the
      players rated the pain during testing on a numerical rating scale (0-10).
      RESULTS: In 4 tests (isometric hip adduction, abduction, flexion, and eccentric
      adduction), no significant correlations were found between pain during testing
      and hip muscle strength (Spearman rho = -0.28 to 0.06, P = 0.09-0.39). Isometric
      hip flexion (modified Thomas test position) showed a moderate negative
      correlation between pain and hip muscle strength (Spearman rho = -0.44, P =
      0.016). CONCLUSIONS: Self-reported pain during testing does not seem to correlate
      with the majority of hip muscle strength tests used in soccer players with long
      standing hip and groin pain.

PMID- 26204043
TI  - Perinatal origin of endometriosis revisited.

PMID- 26204044
TI  - Mood disorders and quality of life in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) affects 5-10% of the population of women. The
      exact etiology of PCOS remains unclear, but it is believed to result from complex
      interactions between genetic, behavioral and environmental factors. The spectrum
      of its symptoms such as hirsutism, skin problems, obesity and finally infertility
      has a huge negative impact on the individuals' psychological and interpersonal
      functioning. PCOS symptoms can lead to significant deterioration in quality of
      life and be highly stressful negatively affecting psychological well-being and
      sexuality. Fear symptoms like palpitation, being out of breath and tension might
      be caused by many somatic diseases. Moreover, detection and continuous thinking
      about illness can lead to significant negative impact on individual functioning
      in society. PCOS may be a factor potentially favoring the occurrence of mood
      disorders and depression. Biological, social and psychological consequences of
      PCOS among women of reproductive age are opening a new perspective on management
      of women's health in these patients. 

PMID- 26204045
TI  - Evolution of the Diagnosis of Functional Gut Disorders: Is an Objective Positive
      Diagnostic Approach Within Reach?

PMID- 26204046
TI  - Indoor air sampling for fine particulate matter and black carbon in industrial
      communities in Pittsburgh.
AB  - Impacts of industrial emissions on outdoor air pollution in nearby communities
      are well-documented. Fewer studies, however, have explored impacts on indoor air
      quality in these communities. Because persons in northern climates spend a
      majority of their time indoors, understanding indoor exposures, and the role of
      outdoor air pollution in shaping such exposures, is a priority issue. Braddock
      and Clairton, Pennsylvania, industrial communities near Pittsburgh, are home to
      an active steel mill and coke works, respectively, and the population experiences
      elevated rates of childhood asthma. Twenty-one homes were selected for 1-week
      indoor sampling for fine particulate matter (PM2.5) and black carbon (BC) during
      summer 2011 and winter 2012. Multivariate linear regression models were used to
      examine contributions from both outdoor concentrations and indoor sources. In the
      models, an outdoor infiltration component explained 10 to 39% of variability in
      indoor air pollution for PM2.5, and 33 to 42% for BC. For both PM2.5 models and
      the summer BC model, smoking was a stronger predictor than outdoor pollution, as
      greater pollutant concentration increases were identified. For winter BC, the
      model was explained by outdoor pollution and an open windows modifier. In both
      seasons, indoor concentrations for both PM2.5 and BC were consistently higher
      than residence-specific outdoor concentration estimates. Mean indoor PM2.5 was
      higher, on average, during summer (25.8+/-22.7 MUg/m3) than winter (18.9+/-13.2
      MUg/m3). Contrary to the study's hypothesis, outdoor concentrations accounted for
      only little to moderate variability (10 to 42%) in indoor concentrations; a much
      greater proportion of PM2.5 was explained by cigarette smoking. Outdoor
      infiltration was a stronger predictor for BC compared to PM2.5, especially in
      winter. Our results suggest that, even in industrial communities of high outdoor
      pollution concentrations, indoor activities--particularly cigarette smoking--may
      play a larger role in shaping indoor exposures.

PMID- 26204047
TI  - Sulfate reducing bacteria and their activities in oil sands process-affected
      water biofilm.
AB  - Biofilm reactors were constructed to grow stratified multispecies biofilm in oil
      sands process-affected water (OSPW) supplemented with growth medium. The
      development of sulfate reducing bacteria (SRB) within the biofilm and the biofilm
      treatment of OSPW were evaluated. The community structure and potential activity
      of SRB in the biofilm were investigated with H2S microsensor measurements, dsrB
      gene-based denaturing gradient gel electrophoresis (DGGE), and the real time
      quantitative polymerase chain reaction (qPCR). Multispecies biofilm with a
      thickness of 1000 MUm was successfully developed on engineered biocarriers. H2S
      production was observed in the deeper anoxic zone of the biofilm from around 750
      MUm to 1000 MUm below the bulk water-biofilm interface, revealing sulfate
      reduction in the deeper zone of the stratified biofilm. The biofilm removed
      chemical oxygen demand (COD), sulfate, and nitrogen. The study expands current
      knowledge of biofilm treatment of OSPW and the function of anaerobic SRB in OSPW
      biofilm, and thus provides information for future bioreactor development in the
      reclamation of OSPW.

PMID- 26204048
TI  - Short-term effects of air pollution on daily mortality and years of life lost in
      Nanjing, China.
AB  - The deteriorating air quality in Chinese cities is attracting growing public
      concern. We conducted analyses to quantify the associations between daily changes
      in ambient air pollution and mortality in Nanjing, China. Daily mortality, air
      pollution, and meteorological data from 1 January 2009 to 31 December 2013 were
      collected. Over-dispersed Poisson regression models were used to evaluate the
      risk of daily non-accidental mortality and years of life lost (YLL) from exposure
      to respirable particulate matter (PM10) and gaseous pollutants (NO2, SO2).
      Stratified analysis was conducted to indentify the modifying effect of individual
      level factors on the association between air pollutants and mortality. We found
      that interquartile range (IQR) increases in the two-day average of PM10, NO2 and
      SO2 were significantly associated with 1.6% [95% confidence interval (CI):0.7%
      2.6%], 2.9% (95% CI: 1.7%-4.2%) and 2.4% (95% CI: 1.2%-3.6%) higher rates of non
      accidental mortality; and related to YLL increases of 20.5 (95% CI: 6.3-34.8),
      34.9 (95% CI: 16.9-52.9) and 30.3 (95% CI: 12.2-48.4) years, respectively;
      Associations between air pollution and mortality were more pronounced in the warm
      season than in the cool season. We conclude that the risks of mortality and YLL
      were elevated corresponding to an increase in current ambient concentrations of
      the air pollutants, and season may modify the effects of outdoor air pollution in
      Nanjing. 

PMID- 26204049
TI  - A strong enrichment of potentially toxic elements (PTEs) in Nord-Trondelag
      (central Norway) forest soil.
AB  - Analysis of soil C and O horizon samples in a recent regional geochemical survey
      of Nord-Trondelag, central Norway (752 sample sites covering 25,000 km2),
      identified a strong enrichment of several potentially toxic elements (PTEs) in
      the O horizon. Of 53 elements analysed in both materials, Cd concentrations are,
      on average, 17 times higher in the O horizon than in the C horizon and other PTEs
      such as Ag (11-fold), Hg (10-fold), Sb (8-fold), Pb (4-fold) and Sn (2-fold) are
      all strongly enriched relative to the C horizon. Geochemical maps of the survey
      area do not reflect an impact from local or distant anthropogenic contamination
      sources in the data for O horizon soil samples. The higher concentrations of PTEs
      in the O horizon are the result of the interaction of the underlying geology, the
      vegetation zone and type, and climatic effects. Based on the general accordance
      with existing data from earlier surveys in other parts of northern Europe, the
      presence of a location-independent, superordinate natural trend towards
      enrichment of these elements in the O horizon relative to the C horizon soil is
      indicated. The results imply that the O and C horizons of soils are different
      geochemical entities and that their respective compositions are controlled by
      different processes. Local mineral soil analyses (or published data for the
      chemical composition of the average continental crust) cannot be used to provide
      a geochemical background for surface soil. At the regional scale used here
      surface soil chemistry is still dominated by natural sources and processes.

PMID- 26204050
TI  - The future of copper in China--A perspective based on analysis of copper flows
      and stocks.
AB  - This study attempts to speculate on the future of copper metabolism in China
      based on dynamic substance flow analysis. Based on tremendous growth of copper
      consumption over the past 63 years, China will depict a substantially increasing
      trend of copper in-use stocks for the next 30 years. The highest peak will be
      possibly achieved in 2050, with the maximum ranging between 163 Mt and 171 Mt.
      After that, total stocks are expected to slowly decline 147-154 Mt by the year
      2080. Owing to the increasing demand of in-use stocks, China will continue to
      have a profound impact on global copper consumption with its high import
      dependence until around 2020, and the peak demand for imported copper are
      expected to approach 5.5 Mt/year. Thereafter, old scrap generated by domestic
      society will occupy an increasingly important role in copper supply. In around
      2060, approximately 80% of copper resources could come from domestic recycling of
      old scrap, implying a major shift from primary production to secondary
      production. With regard to the effect of lifetime distribution uncertainties in
      different end-use sectors of copper stocks on the predict results, uncertainty
      evaluation was performed and found the model was relatively robust to these
      changes.

PMID- 26204051
TI  - Intra-urban variation of ultrafine particles as evaluated by process related land
      use and pollutant driven regression modelling.
AB  - The microscale intra-urban variation of ultrafine particle concentrations (UFP,
      diameter Dp<100 nm) and particle number size distributions was studied by two
      statistical regression approaches. The models were applied to a 1 km2 study area
      in Braunschweig, Germany. A land use regression model (LUR) using different urban
      morphology parameters as input is compared to a multiple regression type model
      driven by pollutant and meteorological parameters (PDR). While the LUR model was
      trained with UFP concentration the PDR model was trained with measured particle
      number size distribution data. The UFP concentration was then calculated from the
      modelled size distributions. Both statistical approaches include explanatory
      variables that try to address the 'process chain' of particle emission, dilution
      and deposition. LUR explained 74% and 85% of the variance of UFP for the full
      data set with a root mean square error (RMSE) of 668 cm(-3) and 1639 cm(-3) in
      summer and winter, respectively. PDR explained 56% and 74% of the variance with
      RMSE of 4066 cm(-3) and 6030 cm(-3) in summer and winter, respectively. Both
      models are capable to depict the spatial variation of UFP across the study area
      and in different outdoor microenvironments. The deviation from measured UFP
      concentrations is smaller in the LUR model than in PDR. The PDR model is well
      suited to predict urban particle number size distributions from the explanatory
      variables (total particle number concentration, black carbon and wind speed). The
      urban morphology parameters in the LUR model are able to resolve size dependent
      concentration variations but not as adequately as PDR.

PMID- 26204052
TI  - A new framework for evaluating the impacts of drought on net primary productivity
      of grassland.
AB  - This paper presented a valuable framework for evaluating the impacts of droughts
      (single factor) on grassland ecosystems. This framework was defined as the
      quantitative magnitude of drought impact that unacceptable short-term and long
      term effects on ecosystems may experience relative to the reference standard.
      Long-term effects on ecosystems may occur relative to the reference standard. Net
      primary productivity (NPP) was selected as the response indicator of drought to
      assess the quantitative impact of drought on Inner Mongolia grassland based on
      the Standardized Precipitation Index (SPI) and BIOME-BGC model. The framework
      consists of six main steps: 1) clearly defining drought scenarios, such as
      moderate, severe and extreme drought; 2) selecting an appropriate indicator of
      drought impact; 3) selecting an appropriate ecosystem model and verifying its
      capabilities, calibrating the bias and assessing the uncertainty; 4) assigning a
      level of unacceptable impact of drought on the indicator; 5) determining the
      response of the indicator to drought and normal weather state under global
      change; and 6) investigating the unacceptable impact of drought at different
      spatial scales. We found NPP losses assessed using the new framework were more
      sensitive to drought and had higher precision than the long-term average method.
      Moreover, the total and average losses of NPP are different in different
      grassland types during the drought years from 1961-2009. NPP loss was
      significantly increased along a gradient of increasing drought levels. Meanwhile,
      NPP loss variation under the same drought level was different in different
      grassland types. The operational framework was particularly suited for
      integrative assessing the effects of different drought events and long-term
      droughts at multiple spatial scales, which provided essential insights for
      sciences and societies that must develop coping strategies for ecosystems for
      such events. 

PMID- 26204053
TI  - Changes in land use, climate and the environment during a period of rapid
      economic development in Jiangsu Province, China.
AB  - Understanding changes in climate and environment on a regional scale can provide
      useful guidance for regional socio-economic development. The present study
      characterizes changes in the environment, climate, land use and cover types via
      in situ observed, statistical data and remote sensing images for Jiangsu
      Province, China, during the period 1980-2012. Statistical and spatial analyses
      indicate that the pace of urbanization in southern Jiangsu is more rapid than
      that in northern Jiangsu. Urbanization (92.7%) results primarily from the loss of
      farmland. While emissions of pollutants from industrial sources were well
      controlled, and wastewater, which more frequently derives from urban domestic
      sources, was found to be increasing. The rates of wastewater to population
      increased from 0.17+/-0.017 to 0.32+/-0.090 (billion ton/million persons) during
      the two periods of 1980-2000 and 2000-2012. However, the rates of wastewater to
      Gross Domestic Product (GDP) decreased from 0.26+/-0.20 to 0.014+/-0.009 (billion
      ton/billion Yuan), respectively. The significant increase in scattering radiance
      and Earth's albedo caused by the urbanization and its process (Pearson
      correlation coefficient (r) between urban land and scattering radiance=0.86,
      p<0.0001; r between farmland and scattering radiance=-0.92, p<0.0001) aggravates
      the warming in the regional scale. This correlation analysis indicates that
      temperature will decrease with the increase of woodland, grassland and farmland,
      and will increase with the increase of urbanized and unexploited lands. Added to
      warming caused by an increase in CO2, land use/cover change and human activities
      may be the primary reason for the rising temperatures in Jiangsu Province. The
      change in regional thermal conditions reduces both local humidity and land
      atmosphere flux exchange. The low atmosphere flux exhange contributes to the
      spread of atmospheric pollutants and the deposition of atmospheric particles.

PMID- 26204054
TI  - Frequent cellular phone use modifies hypothalamic-pituitary-adrenal axis response
      to a cellular phone call after mental stress in healthy children and adolescents:
      A pilot study.
AB  - OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA) axis is the main "gate
      keeper" of the organism's response to every somatic or mental stress. This
      prospective study aims to investigate the HPA-axis response to a cellular phone
      call exposure after mental stress in healthy children and adolescents and to
      assess the possible predictive role of baseline endocrine markers to this
      response. SUBJECTS AND METHODS: Two groups of healthy school-age children aged 11
      14 (12.5+/-1.5) years were included in the study, the one comprising those who
      are occasional users of a cellular phone (Group A) while the second those who do
      regularly use one (Group B). Blood samples were obtained from all participants at
      8.00 am after a 12-hour overnight fasting for thyroid hormone, glucose, insulin,
      and cortisol levels determination. The participants performed the Trier Social
      Stress Test for Children (TSST-C) (5 minoral task followed by 5 min arithmetic
      task). Salivary cortisol samples were obtained at baseline, 10' and 20' min after
      the TSST-C and 10' and 20' after a 5 minute cellular phone call. RESULTS:
      Significant changes in the salivary cortisol levels were noted between 10' and
      20' mins after the cellular phone call with different responses between the two
      groups. Baseline thyroid hormone levels seem to predict the cortisol response to
      mental stress mainly in group A, while HOMA had no impact on salivary cortisol
      response at any phase of the test, in either group. CONCLUSIONS: HPA axis
      response to cellular phone after mental stress in children and adolescents follow
      a different pattern in frequent users than in occasional users that seems to be
      influenced by the baseline thyroid hormone levels.

PMID- 26204055
TI  - An assessment of health risks associated with arsenic exposure via consumption of
      homegrown vegetables near contaminated glassworks sites.
AB  - The health risk posed by arsenic in vegetables grown in private gardens near 22
      contaminated glassworks sites was investigated in this study. Firstly, vegetable
      (lettuce and potato) and soil samples were collected and arsenic concentrations
      measured to characterize the arsenic uptake in the selected crops. Secondly, a
      probabilistic exposure assessment was conducted to estimate the average daily
      intake (ADIveg), which was then evaluated against toxicological reference values
      by the calculation of hazard quotients (HQs) and cancer risks (CRs). The results
      show that elevated arsenic concentrations in residential garden soils are
      mirrored by elevated concentrations in vegetables, and that consumption of these
      vegetables alone may result in an unacceptable cancer risk; the calculated
      reasonable maximum exposure, for example, corresponded to a cancer incidence 20
      times higher than the stated tolerance limit. However, the characterization of
      risk depends to a great extent on which toxicological reference value is used for
      comparison, as well as how the exposure is determined. Based on the assumptions
      made in the present study, the threshold levels for chronic non-carcinogenic or
      acute effects were not exceeded, but the cancer risks indicated highlight the
      need for further exposure studies, as dietary intake involves more than just
      homegrown vegetables and total exposure is a function of more than just one
      exposure pathway. In addition, glassworks sites--and contaminated sites in
      general--contain multiple contaminants, affecting the final and total risk.

PMID- 26204056
TI  - Tryptophan Lyase (NosL): Mechanistic Insights from Substrate Analogues and
      Mutagenesis.
AB  - NosL is a member of a family of radical S-adenosylmethionine enzymes that
      catalyze the cleavage of the Calpha-Cbeta bond of aromatic amino acids. In this
      paper, we describe a set of experiments with substrate analogues and mutants for
      probing the early steps of the NosL mechanism. We provide biochemical evidence in
      support of the structural studies showing that the 5'-deoxyadenosyl radical
      abstracts a hydrogen atom from the amino group of tryptophan. We demonstrate that
      d-tryptophan is a substrate for NosL but shows relaxed regio control of the first
      beta-scission reaction. Mutagenesis studies confirm that Arg323 is important for
      controlling the regiochemistry of the beta-scission reaction and that Ser340
      binds the substrate by hydrogen bonding to the indolic N1 atom.

PMID- 26204057
TI  - Triblock Conjugates: Identification of a Highly Potent Antiinflammatory Agent.
AB  - Rationally designed conjugates of chrysin, indole, and barbituric acid were
      synthesized and screened for their antiinflammatory activities through in vitro
      and in vivo experiments. Improved over the previously reported chrysin-indole
      pyrazole conjugates and also in comparison to the chrysin, indole, and barbituric
      acid based COX-2 inhibitors, the new compounds have displayed significantly
      better IC50 for COX-2 and some of them also exhibited inhibition of 5-LOX enzyme.
      For one of the test compounds, IC50 for COX-2 and 5-LOX was 1 and 1.5 nM,
      respectively. Investigations of Swiss Albino mice through capsaicin induced paw
      lickings and dextran induced inflammation showed that these compounds possess
      appreciable analgesic and antiinflammatory activities. Ki, Ka, and DeltaG for the
      enzyme-compound interaction were calculated and found to be in agreement with the
      biological data. The experimental results were supported by the molecular docking
      studies of the compounds in the active site of COX-2 and 5-LOX. Overall, a highly
      promising antiinflammatory agent was identified. 

PMID- 26204058
TI  - Construction of Benzo[c]carbazoles and Their Antitumor Derivatives through the
      Diels-Alder Reaction of 2-Alkenylindoles and Arynes.
AB  - The direct assembly of benzo[c]carbazole derivatives via the Diels-Alder reaction
      of arynes and easily accessible 2-alkenylidoles was reported. By employing
      different aryne precursor loads, 6,7-dihydrobenzo[c]carbazoles or aryl
      substituted 7,11b-dihydrobenzo[c]carbazoles could be controllably generated in
      good to excellent yields under a nitrogen atmosphere. On the other hand, when the
      reaction was conducted under oxygen, oxidated/aromatized product
      benzo[c]carbazoles could be generated directly with high selectivity and
      efficiency in a one-step manner. Interestingly, the benzo[c]carbazole-5
      carboxamide amidation derivatives of the above products showed good antitumor
      activities. The inhibitory effect of these molecules against cancer cells was
      also described. 

PMID- 26204059
TI  - Different routes, same pathways: Molecular mechanisms under silver ion and
      nanoparticle exposures in the soil sentinel Eisenia fetida.
AB  - Use of nanotechnology products is increasing; with silver (Ag) nanoparticles
      particularly widely used. A key uncertainty surrounding the risk assessment of
      AgNPs is whether their effects are driven through the same mechanism of action
      that underlies the toxic effects of Ag ions. We present the first full
      transcriptome study of the effects of Ag ions and NPs in an ecotoxicological
      model soil invertebrate, the earthworm Eisenia fetida. Gene expression analyses
      indicated similar mechanisms for both silver forms with toxicity being exerted
      through pathways related to ribosome function, sugar and protein metabolism,
      molecular stress, disruption of energy production and histones. The main
      difference seen between Ag ions and NPs was associated with potential
      toxicokinetic effects related to cellular internalisation and communication, with
      pathways related to endocytosis and cilia being significantly enriched. These
      results point to a common final toxicodynamic response, but initial
      internalisation driven by different exposure routes and toxicokinetic mechanisms.

PMID- 26204062
TI  - Full-Dimensional Quantum Dynamics of Vibrational Mediated Photodissociation of
      HOD in Its B Band.
AB  - The photodissociation dynamics for the ground and three fundamental vibrational
      states of HOD were explored from quantum dynamical calculations including the
      electronic X, A, and B states. The calculations were based on a Chebyshev real
      wave packet method. Due to the different shapes of the initial vibrational wave
      functions and isotopic effect, the calculated absorption spectra, product state
      distributions, and branching ratios show different dynamic features. The initial
      bending excited vibtaional state (0, 1, 0) generates a bimodal behavior on the
      absorption spectrum and an inverted vibrational population of OD(X) fragment at
      some total energies. The rotational state distributions from four vibrational
      states have two different behaviors. One has a single broad peak, whereas the
      other one has a bimodal structure. Large OD(A)/OD(X) ratios are found for
      photodissociation from four vibrational states at high total energies, which
      indicate that the H atom dissociates mainly via the adiabatic pathway. We also
      calculated the OD/OH isotopic branching ratios from four vibrational states and
      found that the OD + H production channel is dominant over the OH + D channel in
      the energy range considered. The calculated results are consistent with the
      available observed ones. 

PMID- 26204060
TI  - Preparation of a Two-Dimensional Ion-Imprinted Polymer Based on a Graphene
      Oxide/SiO2 Composite for the Selective Adsorption of Nickel Ions.
AB  - In the present work, a novel two-dimensional (2D) nickel ion-imprinted polymer
      (RAFT-IIP) has been successfully synthesized based on the graphene oxide/SiO2
      composite by reversible addition-fragmentation chain-transfer (RAFT)
      polymerization. The imprinted materials obtained are characterized by Fourier
      transmission infrared spectrometry (FT-IR), scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), X-ray diffraction (XRD), and
      thermogravimetric analysis (TGA). The results show that the thermal stability of
      the graphene oxide/SiO2 composite is obviously higher than that of graphene
      oxide. RAFT-IIP possesses an excellent 2D homogeneous imprinted polymer layer,
      which is a well-preserved unique structure of graphene oxide/SiO2. Owing to the
      intrinsic advantages of RAFT polymerization and 2D imprinted material, RAFT-IIP
      demonstrate a superior specific adsorption capacity (81.73 mg/g) and faster
      adsorption kinetics (30 min) for Ni(II) in comparison to the ion-imprinted
      polymer prepared by traditional radical polymerization and based on the common
      carbon material. Furthermore, the adsorption isotherm and selectivity toward
      Ni(II) onto RAFT-IIP and nonimprinted polymer (NIP) are investigated, indicating
      that RAFT-IIP has splendid recognizing ability and a nearly 3 times larger
      adsorption capacity than that of NIP (30.94 mg/g). Moreover, a three-level Box
      Behnken experimental design with three factors combining the response surface
      method is utilized to optimize the desorption process. The optimal conditions for
      the desorption of Ni(II) from RAFT-IIP are as follows: an HCl-type eluent, an
      eluent concentration of 2.0 mol/L, and an eluent volume of 10 mL. 

PMID- 26204061
TI  - High Selective Performance of Designed Antibacterial and Anticancer Peptide
      Amphiphiles.
AB  - Short designed peptide amphiphiles are attractive at killing bacteria and
      inhibiting cancer cell growth, and the flexibility in their structural design
      offers a great potential for improving their potency and biocompatibility to
      mammalian host cells. Amino acid sequences such as G(IIKK)nI-NH2 (n>=3) have been
      shown to be membrane lytic, but terminal amino acid modifications could impose a
      huge influence on their performance. We report in this work how terminal amino
      acid modifications to G(IIKK)3I-NH2 influence its alpha-helical structure,
      membrane penetrating ability, and selective actions against different cell types.
      Deletion of an N-terminal Gly or a C-terminal Ile did not affect their
      antibacterial activity much, an observation consistent with their binding
      behavior to negatively charged membrane lipid monolayers. However, the
      cytotoxicity against mammalian cells was much worsened by the N-terminal Gly
      deletion, consistent with an increase in its helical content. Despite little
      impact on the antibacterial activity of G(IIKK)3I-NH2, deletion of both terminal
      amino acids greatly reduced its antitumor activity. Cholesterol present in tumor
      cell membrane-mimic was thought to constrain (IIKK)3-NH2 from penetrating into
      the cancerous membranes, evident from its lowest surface physical activity at
      penetrating model lipid membranes. On the other hand, its low toxicity to normal
      mammalian cells and high antibacterial activity in vitro and in vivo made it an
      attractive antibacterial agent. Thus, terminal modifications can help rebalance
      the different interactions involved and are highly effective at manipulating
      their selective membrane responses.

PMID- 26204063
TI  - Copper(I)-Catalyzed Kinetic Resolution of N-Sulfonylaziridines with Indoles:
      Efficient Construction of Pyrroloindolines.
AB  - The first Lewis acid catalyzed [3 + 2] annulation of indoles and 2-aryl-N
      tosylaziridines was realized by using copper(I)/chiral diphosphine complexes as a
      catalyst. With this method, a variety of uniquely substituted chiral
      pyrroloindolines bearing multiple contiguous stereogenic centers were facilely
      accessed in a straightforward, high-yielding, and highly stereoselective way
      under mild conditions. 

PMID- 26204064
TI  - Photocatalytic removal of 2-nitrophenol using silver and sulfur co-doped
      TiO2under natural solar light.
AB  - To overcome the drawback of poor solar light utilization brought about by the
      narrow photoresponse range of TiO2, a silver and sulfur co-doped TiO2was
      synthesized. Using the prepared catalyst, solar photocatalytic degradation of 2
      nitrophenol (2-NP) by a TiO2-based catalyst was studied for the first time.
      Effects of the co-doping on the structural, optical and morphological properties
      of the synthesized nanoparticles were investigated by different characterization
      methods: X-ray diffraction, N2 adsorption-desorption measurements, scanning
      electron microscopy, transmission electron microscopy, energy-dispersive X-ray
      spectroscopy, UV-visible diffuse reflectance spectroscopy and Fourier transform
      infrared spectroscopy. Solar experiments showed that the co-doping with silver
      and sulfur significantly increased the photocatalytic activity. In various
      initial concentrations of 2-NP more than 99% of the contaminant was decomposed by
      Ag-S/TiO2in less than 150 minutes, while the degradation efficiency was much less
      in the presence of bare TiO2. Kinetic studies suggested that solar photocatalytic
      degradation of 2-NP is consistent with the Langmuir-Hinshelwood model. The rate
      constant of the reaction and adsorption constant of the modified photocatalyst
      were found to be 2.4 and 4.1 times larger than that of bare TiO2, respectively.

PMID- 26204065
TI  - Biodegradability of some nitrogenous heterocyclic compounds and co-degradation
      with phenol by denitrifiers in anoxic sludge reactor.
AB  - Phenol and nitrogenous heterocyclic compounds (NHCs) are typical organic
      pollutants in coal gasification wastewater which are difficult to deal with.
      Unlike phenol, the stable molecular structure of NHCs make them nearly impossible
      to degrade under aerobic or anaerobic condition. In this paper, biodegradation of
      phenol and NHCs as carbon sources for denitrification was studied in a laboratory
      scale anoxic reactor. Denitrifiers could degrade 490 mg/L phenol and 321.5 mg/L
      NO3(-)-N within 12 hours with removal efficiencies of 99.8% and 99.6%,
      respectively. The inhibition of pyridine on the microbes could be reduced by
      adding phenol into influent and the experimental results showed that pyridine
      could be degraded as the sole carbon source with the maximum organic loading rate
      of 4.38 mg/(g MLSS.h) (MLSS: mixed liquor suspended solids). When phenol was
      included as a growth substrate, the degradation performance of quinoline and
      pyrrole was improved due to co-degradation, and removal rate of NHCs increased
      according with increment of phenol in influent. 

PMID- 26204066
TI  - Evaluation of environmental flow requirements using eco-hydrologic-hydraulic
      methods in perennial rivers.
AB  - The assessment of environmental flows in rivers is of vital importance for
      preserving riverine ecosystem processes. This paper addresses the evaluation of
      environmental flow requirements in three reaches along a typical perennial river
      (the Zab transboundary river, in north-west Iran), using different hydraulic,
      hydrological and ecological methods. The main objective of this study came from
      the construction of three dams and inter-basin transfer of water from the Zab
      River to the Urmia Lake. Eight hydrological methods (i.e. Tennant, Tessman, flow
      duration curve analysis, range of variability approach, Smakhtin, flow duration
      curve shifting, desktop reserve and 7Q2&10 (7-day low flow with a 2- and 10-year
      return period)); two hydraulic methods (slope value and maximum curvature); and
      two habitat simulation methods (hydraulic-ecologic, and Q Equation based on water
      quality indices) were used. Ecological needs of the riverine key species (mainly
      Barbus capito fish), river geometries, natural flow regime and the environmental
      status of river management were the main indices for determining the minimum flow
      requirements. The results indicate that the order of 35%, 17% and 18% of the mean
      annual flow are to be maintained for the upper, middle and downstream river
      reaches, respectively. The allocated monthly flow rates in the three Dams
      steering program are not sufficient to preserve the Zab River life. 

PMID- 26204067
TI  - Sludge reduction in a small wastewater treatment plant by electro-kinetic
      disintegration.
AB  - Sludge reduction in a wastewater treatment plant (WWTP) has recently become a key
      issue for the managing companies, due to the increasing constraints on the
      disposal alternatives. Therefore, all the solutions proposed with the aim of
      minimizing sludge production are receiving increasing attention and are tested
      either at laboratory or full-scale to evaluate their real effectiveness. In the
      present paper, electro-kinetic disintegration has been applied at full-scale in
      the recycle loop of the sludge drawn from the secondary settlement tank of a
      small WWTP for domestic sewage. After the disintegration stage, the treated
      sludge was returned to the biological reactor. Three different percentages (50,
      75 and 100%) of the return sludge flow rate were subjected to disintegration and
      the effects on the sludge production and the WWTP operation efficiency evaluated.
      The long-term observations showed that the electro-kinetic disintegration was
      able to drastically reduce the amount of biological sludge produced by the plant,
      without affecting its treatment efficiency. The highest reduction was achieved
      when 100% return sludge flow rate was subjected to the disintegration process.
      The reduced sludge production gave rise to a considerable net cost saving for the
      company which manages the plant. 

PMID- 26204068
TI  - Mild desalination of various raw water streams.
AB  - For chemical industries, fresh water availability is a pre-requisite for
      sustainable operation. However, in many delta areas around the world, fresh water
      is scarce. Therefore, the E4 Water project (www.e4water.eu) comprises a case
      study at the Dow site in Terneuzen, The Netherlands, which is designed to develop
      commercial applications for mild desalination of brackish raw water streams from
      various origins to enable reuse in industry or agriculture. This study describes
      an effective two-stage work process, which was used to narrow down a broad
      spectrum of desalination technologies to a selection of the most promising
      techniques for a demonstration pilot at 2-4 m3/hour. Through literature study,
      laboratory experiments and multi-criteria analysis, nanofiltration and
      electrodialysis reversal were selected, both having the potential to attain the
      objectives of E4Water at full scale.

PMID- 26204069
TI  - Nitrate removal by nitrate-dependent Fe(II) oxidation in an upflow denitrifying
      biofilm reactor.
AB  - A continuous upflow biofilm reactor packed with ceramsite was constructed for
      nitrate removal under an anaerobic atmosphere without an organic carbon source.
      Denitrifying bacteria, Pseudomonas sp. W1, Pseudomonas sp. W2 and Microbacterium
      sp. W5, were added to the bioreactor as inocula. Nitrate concentration, nitrite
      accumulation and nitrogen removal efficiency in the effluent were investigated
      under various conditions set by several parameters including pH, hydraulic
      retention time (HRT), ratios of carbon to nitrogen (C/N) and temperature. The
      results illustrated that the maximum removal efficiency of nitrogen was 85.39%,
      under optimum reaction parameters, approximately pH 6.5-7, HRT = 48 hours and C/N
      = 13.1:1 at temperature of 30  degrees C, which were determined by experiment. 

PMID- 26204070
TI  - Effect of organic loading rate on the performance of two-stage anaerobic
      digestion of the organic fraction of municipal solid waste (OFMSW).
AB  - Two-stage anaerobic digestion of the organic fraction of municipal solid waste
      (OFMSW) was carried out: hydrolysis and acidogenesis in a continuous anaerobic
      hydrolytic leach bed (AHLB) reactor loaded at different rates (Bv = 3.8-7 gVSSL
      1d-1) and methanogenesis of leachates, diluted with municipal wastewater in an
      upflow anaerobic sludge blanket (UASB) reactor at organic loading rates of 6.6-13
      gCODLr-1d-1. In the AHLB reactor, 51-76% and 58-71% volatile solids and chemical
      oxygen demand (COD) removal efficiencies were obtained. During the hydrolysis and
      acidogenesis phases, the effluents were at pH 4.93, the leachate had a volatile
      fatty acids concentration of 35 g/L and the biogas was composed only of CO2. The
      average methane production in the UASB in the load of 4.4 gVS L-1 d-1 in the AHLB
      was 3.32 LCH4Lr-1d-1 (yCH4 = 80%), with COD removal efficiency of 95% and methane
      yield 279 LCH4KgVS-1OFMSW degraded.

PMID- 26204071
TI  - A logistic model for the remediation of filamentous bulking in a biological
      nutrient removal wastewater treatment plant.
AB  - Biological nutrient removal (BNR) systems across the globe frequently experience
      bulking and foaming episodes, which present operational challenges such as poor
      sludge settling due to excessive filamentous bacteria. A full-scale BNR plant
      treating primarily domestic wastewater was monitored over a period of 1 year to
      investigate filamentous bacterial growth response under various plant operating
      parameters. Identification of filamentous bacteria by conventional microscopy and
      fluorescent in situ hybridisation indicated the dominance of Eikelboom Type021N,
      Thiothrix spp., Eikelboom Type 1851 and Eikelboom Type 0092. A cumulative logit
      model (CLM) was applied to elucidate significant relationships between the
      filamentous bacteria and plant operational parameters. The model could predict
      the potential abundance of dominant filamentous bacteria in relation to
      wastewater treatment plant operational parameters. Data obtained from the model
      corroborated with previous findings on the dominance of most filaments
      identified, except for Type 0092, which exhibited some unique traits. With
      further validation, the model could be successfully applied for identifying
      specific parameters which could contribute towards filamentous bulking, thus,
      providing a useful tool for regulating specific filamentous growth in full-scale
      wastewater treatment plants. 

PMID- 26204072
TI  - Enhanced coagulation with in situ manganese dioxide on removal of humic acid in
      micro-polluted water.
AB  - The morphology and surface characteristics of manganese dioxide (MnO2) formed in
      situ, which was prepared through the oxidation of MnSO4using KMnO4, were studied.
      The effects of factors including the form of MnO2, dosage, pH, dosing sequence of
      in situ MnO2on the enhanced coagulation were systematically evaluated. The
      results of analysis by the UV254 and permanganate index CODMn methods indicated
      that humic acid removal increased from 9.2 and 2.5% to 55.0 and 38.9%, when 10
      mg/L of the in situ MnO2 was added in the presence of 2 mg/L of polyaluminum
      sulfate. The studies of orthogonal experiment revealed that coagulation was most
      affected by the pH, whereas the dosage of in situ MnO2and slow stirring duration
      exhibited a weaker effect. At a pH value of 4.0, in situ MnO2dosage of 10 mg/L,
      slow stir over 40 min, and the total solids content was 20 mg/L, the humic acid
      removal by UV254 and CODMn methods reached 71.2 and 61.2%. These results
      indicated that the presence of in situ MnO2enhanced the coagulation and removal
      of humic acid from water.

PMID- 26204073
TI  - Conversion of sewage sludge to commodity chemicals via syngas fermentation.
AB  - Gasification of sewage sludge allows the recovery of energy, and produces a mix
      of CO, CO2and H2called synthesis gas (or syngas), which can be fermented by
      acetogenic bacteria to added-value products. This work presents the conversion of
      syngas to organic acids and alcohols using both pure and mixed cultures. Pure
      culture kinetic experiments with Clostridium carboxidivorans P7 resulted in the
      production of high concentrations of acetate (454 mgC/L) and ethanol (167 mgC/L).
      The pH was the main factor driving solventogenesis, with about 50% of the
      products in the form of alcohols at pH 5. Conversely, laboratory-scale
      experiments using a carboxydotrophic mixed culture of the genus Clostridium
      enriched from anaerobic digester sludge of a municipal wastewater treatment plant
      was capable of producing mainly butyrate, with maximum concentration of 1,184
      mgC/L.

PMID- 26204074
TI  - Operating a two-stage microbial fuel cell-constructed wetland for fuller
      wastewater treatment and more efficient electricity generation.
AB  - By integrating microbial fuel cells (MFCs) into constructed wetlands (CWs) the
      need and cost of building a reactor are eliminated, while CWs provide the
      simultaneous redox conditions required for optimum MFC performance. Two single
      stage MFC-CWs, with dewatered alum sludge cake as the main wetland medium for
      enhanced phosphorus removal, were operated to determine the effects of electrode
      separation and flow regimes on power production and wastewater treatment. When
      the anode is buried and the cathode is at the air-water interface the system is
      inhibited by a large ohmic resistance resulting from the increased electrode
      separation. By placing the cathode directly above the anode and operating the
      system with simultaneous up-flow into the anode and down-flow into the cathode
      the ohmic resistance is reduced. The chemical oxygen demand (COD) removal
      efficiency was, however, reduced to 64% (compared with 79%). A two-stage system
      was subsequently run for fuller wastewater treatment and increased power
      production. The results indicate that a two-stage MFC-CW can increase the
      normalized energy recovery and improve removal efficiencies of COD, total
      nitrogen, NH4+, total phosphorus and reactive phosphorus to 93 +/- 1.7%, 85 +/-
      5.2%, 90 +/- 5.4%, 98 +/- 5.3% and 99 +/- 2.9%, respectively.

PMID- 26204075
TI  - The positive effects of waste leachate addition on methane fermentation from food
      waste in batch trials.
AB  - The purposes of this study were to investigate the effect of waste leachate (WL)
      addition on batch anaerobic digestion of food waste (FW), and to examine the
      influence of mixture ratio on the co-digestion process. The results showed that
      anaerobic digestion of FW was greatly enhanced by WL addition, as indicated by
      the higher methane yield, higher methane content, more volatile solids (VS)
      destruction, and higher stability. Although WL was rich in volatile fatty acids
      (VFA), its addition did not cause VFA inhibition. It was found that WL addition
      was beneficial to accelerate the start-up and shorten the long reaction time of
      the batch anaerobic process. The time to reach the peak methane yield was reduced
      by 1, 2, and 4 days with WL addition. The optimum FW to WL ratio was 77.9:22.1
      with the highest methane yield (416 mL/g VS), the highest methane content
      (64.3%), the greatest VS removal (77.6%), and stable performance. These results
      confirmed the positive effects of WL addition on methane fermentation from FW. 

PMID- 26204076
TI  - Vanadium(V) removal from aqueous solution and real wastewater using quaternized
      pine sawdust.
AB  - Cross-linked and quaternized pine sawdust was tested for vanadium removal from a
      synthetic aqueous solution as well as from real industrial wastewater which had a
      considerable amount of vanadium and other ions such as sulphate, ammonium and
      nickel. The maximum vanadium sorption capacity of the modified pine sawdust was
      found to be 130 mg/g in synthetic solution and 103 mg/g in real wastewater.
      Modified pine sawdust worked well over a wide range of pH. Column studies with
      real wastewater proved that vanadium was efficiently desorbed from the material
      with 2 M NaOH and that the material could be reused. 

PMID- 26204077
TI  - A new photo-activated sludge system for nitrification by an algal-bacterial
      consortium in a photo-bioreactor with biomass recycle.
AB  - Wastewater treatment technologies requiring large areas may be less feasible in
      urbanizing regions of developing countries. Therefore, a new technology, named
      photo-activated sludge (PAS), was investigated to combine the advantages of
      regular activated sludge systems with those of algae ponds for the removal of
      ammonium. The PAS consisted of a mixed photo-bioreactor, continuously fed with BG
      11 medium, adjusted to 66 mgN-NH4+/l. The reactor volume was 2 l, hydraulic
      retention time was 24 hours, with a depth of 8 cm, and continuous illumination at
      the water surface was 66 MUmol PAR/m2/s (photosynthetically active radiation).
      Reactor effluent passed through a settler and settled biomass was returned to the
      reactor. A well settling biomass developed, that contained both algae and
      nitrifiers. Effluent contained 10 mgN-NH4+/L and 51 mgN-NOx-/L. Using a
      simplified model, the specific algae growth rate was estimated at about 0.62 day
      1, which was within the expected range. For nitrifiers (ammonia oxidizers), the
      specific growth rate was 0.11 day-1, which was lower than reported for regular
      activated sludge. The in-situ photo-oxygenation process by algae contributed 82%
      of the oxygen input, whereas oxygen diffusion through the mixed surface provided
      the remaining 18%. The foreseen energy savings that a PAS system could achieve
      warrant further investigations with real wastewater.

PMID- 26204078
TI  - Study of Pb2+, Cd2+ and Ni2+ adsorption onto activated carbons prepared from
      glycyrrhiza residue by KOH or H3PO4activation.
AB  - The activated carbons (ACs) were prepared from glycyrrhiza residue by KOH or
      H3PO4activation and were used for removing Pb2+, Cd2+ and Ni2+ from simulated
      wastewater. The changes of the physical structure and chemical properties of the
      glycyrrhiza residue before and after activation were characterized by using a
      variety of analytical instruments and methods. Kinetics and equilibrium isotherms
      were obtained and the effects of solution pH value and adsorbent dosage were
      studied in batch experiments. The results indicated that after activation, the
      surface structure of glycyrrhiza residue changes and surface area, micropore
      volume also increase accordingly. Kinetic studies showed that the adsorption
      followed a pseudo-second-order reaction. The Freundlich model fitted the
      equilibrium data better than the Langmuir isotherm. According to the Langmuir
      equation, the maximum adsorption capacities of ACs prepared from glycyrrhiza
      residue by KOH and H3PO4activation for Pb2+, Cd2+ and Ni2+ are 2.170 mmol/g,
      2.617 mmol/g, 3.741 mmol/g and 2.654 mmol/g, 3.095 mmol/g, 3.076 mmol/g,
      respectively, which are much higher than ACs prepared from other raw materials.

PMID- 26204079
TI  - Occurrence and efficacy of bisphenol A (BPA) treatment in selected municipal
      wastewater treatment plants, Bangkok, Thailand.
AB  - Investigations were carried out on the occurrence and fate of bisphenol A (BPA)
      in five wastewater treatment plants (WWTPs) in Bangkok, namely, Rattanakosin,
      Chong Non Si, Din Daeng (DD), Nong Khaem and Thungkru (TK) during three sampling
      events between October 2013 and February 2014. Based on the results, the influent
      and effluent BPA concentrations ranged between 128.5 ng/L and 606.0 ng/L; and
      38.7 ng/L and 270.5 ng/L, respectively. The effluent BPA concentrations of most
      of the five WWTPs were lower than the influent levels. TK had the highest removal
      efficiency in October 2013 (80.4%) and December 2013 (90.7%) and the second
      highest in February 2014 (69.2%). DD had the highest removal efficiency in
      February 2014 (91.8%). The treatment processes employed at TK and DD were
      vertical loop reactor activated sludge process and activated sludge with
      nutrients removal, respectively. Thus, these processes seem to be good for BPA
      degradation. 

PMID- 26204080
TI  - Magnesium ions improving the growth and organics reduction of Rhodospirillum
      rubrum cultivated in sewage through regulating energy metabolism pathways.
AB  - Rhodospirillum rubrum has the potential for biomass resource recycling combined
      with sewage purification. However, low biomass production and yield restricts the
      potential for sewage purification. This research investigated the improvement of
      biomass production, yield and organics reduction by Mg2+ in R. rubrum wastewater
      treatment. Results showed that with optimal dosage (120 mg/L), biomass production
      reached 4,000 mg/L, which was 1.5 times of that of the control group. Biomass
      yield was improved by 43.3%. Chemical oxygen demand (COD) removal reached over
      90%. Hydraulic retention time was shortened by 25%. Mechanism analysis indicated
      that Mg2+ enhanced the isocitrate dehydrogenase and Ca2+/Mg2+-ATPase activities,
      bacteriochlorophyll content on respiration and photophosphorylation. These
      effects then enhanced ATP production, which led to more biomass accumulation and
      COD removal. With 120 mg/L Mg2+ dosage, the isocitrate dehydrogenase and
      Ca2+/Mg2+-ATPase activities, bacteriochlorophyll content, ATP production were
      improved, respectively, by 33.3%, 50%, 67%, 41.3% compared to those of the
      control group.

PMID- 26204081
TI  - Rapid removal of caffeine in aqueous solutions by peroxymonosulfate oxidant
      activated with cobalt ion.
AB  - The removal of caffeine (CAF) in aqueous solution by peroxymonosulfate oxidant
      activated with cobalt ion was investigated under a variety of operating
      conditions. The effects of various operating parameters, such as oxone and Co2+
      concentrations, pH value, and the coexistence of dissolved organic matter and
      inorganic anions on the removal of CAF have been investigated. The removal
      efficiency increased with the increase in the concentrations of oxone and Co2+
      ion added. The additions of chloride, bicarbonate, and sodium humate have
      negative effects on the removal of CAF. Near-neutral condition (5.0 < pH < 7.0)
      is favorable for the removal of CAF. Based on our experiments, 100% degradation
      of 50 mg/L CAF can be achieved within 4 minutes under the conditions of 1.00 mM
      oxone and 0.10 mM Co2+ ion at pH 5.0-7.0.

PMID- 26204082
TI  - The use of simulated rainfall to study the discharge process and the influence
      factors of urban surface runoff pollution loads.
AB  - An understanding of the characteristics of pollutants on impervious surfaces is
      essential to estimate pollution loads and to design methods to minimize the
      impacts of pollutants on the environment. In this study, simulated rainfall
      equipment was constructed to investigate the pollutant discharge process and the
      influence factors of urban surface runoff (USR). The results indicated that
      concentrations of total suspended solids (TSS), total nitrogen (TN), total
      phosphorus (TP) and chemical oxygen demand (COD) appeared to be higher in the
      early period and then decreased gradually with rainfall duration until finally
      stabilized. The capacity and particle size of surface dust, rainfall intensity
      and urban surface slopes affected runoff pollution loads to a variable extent.
      The loads of TP, TN and COD showed a positive relationship with the surface dust
      capacity, whereas the maximum TSS load appeared when the surface dust was 0.0317
      g.cm-2. Smaller particle sizes (<0.125 mm) of surface dust generated high TN, TP
      and COD loads. Increases in rainfall intensity and surface slope enhanced the
      pollution carrying capacity of runoff, leading to higher pollution loads.
      Knowledge of the influence factors could assist in the management of USR
      pollution loads.

PMID- 26204084
TI  - Corrigendum: Water Science and Technology 71 (10), 1463-1470: An ecological
      compensation standard based on emergy theory for the Xiao Honghe River Basin,
      Xinjian Guan, Moyu Chen and Caihong Hu.

PMID- 26204083
TI  - Removal and transformation products of ibuprofen obtained during ozone- and
      ultrasound-based oxidative treatment.
AB  - The oxidation of ibuprofen (IBP) in water was evaluated using oxidative
      treatments: ozonation, sonication, hydrogen peroxide addition and combinations of
      these processes. After 20 minutes of treatment, ozone coupled with hydrogen
      peroxide at pH 7, 15  degrees C, an ozone dose of 16 mg/L and a hydrogen peroxide
      concentration of 7.1 mg/L was found to have the highest IBP (95%) and chemical
      oxygen demand (COD) (41%) removals. A synergistic effect was observed for the
      combined ozonation/sonication process, which might be explained by an improved
      mass transfer of ozone in the solution due to the presence of ultrasonic pressure
      waves. Transformation products were detected in the treated solutions. The nature
      of five of these products was confirmed by liquid chromatography-mass
      spectrometry (LC-MS), including 4-isobutylacetophenone (4-IBAP), oxo-IBP, 4
      acetylbenzoic acid, 4-ethybenzaldehyde and oxalic acid. In addition, COD analyses
      for each experiment showed that the ratio of %COD removal to %IBP removal was
      highest with sonication; suggesting that this oxidative process offers other
      mechanisms of removal which may lead to further degradation of products formed.
      This study presents the first data on removal of IBP by sonication coupled to
      ozonation and provides some insight into the potential of this combined treatment
      approach for the removal of contaminants of emerging concern. 

PMID- 26204085
TI  - [Compliance of the guidelines of the Spanish Neurology Society in the treatment
      of patients with multiple sclerosis].
AB  - INTRODUCTION: Treatment of multiple sclerosis is based on the administration of
      the disease modifying drugs (DMD), used to slow the natural course of the
      disease. AIM: To assess the degree of compliance of Spanish neurologists with
      2010 Spanish Neurology Society (SEN) treatment guidelines. PATIENTS AND METHODS:
      Observational, retrospective and multicenter study of 218 adult patients with at
      least five years of disease evolution and under treatment with DMD. Data on their
      past/current management was obtained from their medical records and descriptively
      compared to SEN recommendations. RESULTS: According to SEN 2010 guidelines, 82%
      of patients had an adequate clinical response and 18% had an inadequate clinical
      response to their current DMD; 94% and 92%, respectively, maintained that
      treatment. Patients in which inadequate clinical response did not motivate a
      change in the current DMD more frequently had higher disability decline and
      higher number of relapses during previous treatments, and longer treatment
      duration with their current DMD. Regarding the sequence of DMDs used, 48% of
      patients initiated first-line treatment with interferon beta-1a administered
      through subcutaneous (29%) or intramuscular injections (19%), followed by
      interferon beta-1b, and glatiramer acetate. Some patients received second-line
      treatments as second/third option (15% and 28% respectively), but these
      treatments (mostly natalizumab) were only widespread from fourth treatment
      onwards. CONCLUSIONS: In accordance with SEN 2010 guidelines, the majority of
      patients from the study had an adequate clinical response. A high percentage of
      patients with an inadequate clinical response remained with their current
      treatment. An explanation to this phenomenon could be found in the chronic,
      complex and variable nature of multiple sclerosis.

PMID- 26204086
TI  - [Delayed neurological syndrome following carbon monoxide poisoning].
AB  - INTRODUCTION: Poisoning by carbon monoxide is the most frequent form of
      intoxication in our milieu as a result of exposure to poisonous gases. The
      effects of carbon monoxide poisoning are not limited to acute exposure, since,
      following apparent recovery from the acute intoxication, neurological or
      behavioural disorders may appear. PATIENTS AND METHODS: A study was conducted to
      examine the cases of carbon monoxide poisoning that had occurred in a healthcare
      area of 80,000 inhabitants over a 10-year period. These patients were then
      submitted to a follow-up to appraise the appearance of delayed neurological
      syndrome (DNS) and its relationship with different variables in the initial
      exposure to the carbon monoxide, in the treatment that was administered or in the
      severity of the intoxication. RESULTS AND CONCLUSIONS: It was observed that
      around 9.1% of those intoxicated by carbon dioxide detected within the healthcare
      district of Salnes went on to develop DNS, which is more frequent in patients
      with severe analytical criteria and very unlikely in those who do not have them.
      Patients with DNS did not express any clinical or analytical manifestations that
      differed from those who did not have the syndrome; no differences were observed
      in relation to the oxygen therapy that was administered. The rate of DNS within
      the healthcare district of Salnes between 2002 and 2012 is 0.84 cases per 100,000
      inhabitants per year.

PMID- 26204087
TI  - [Drug resistant epilepsy. Clinical and neurobiological concepts].
AB  - Drug-resistant epilepsy, is a condition defined by the International League
      Against Epilepsy as persistent seizures despite having used at least two
      appropriate and adequate antiepileptic drug treatments. Approximately 20-30% of
      patients with epilepsy are going to be resistant to antiepileptic drugs, with
      different patterns of clinical presentation, which are related to the biological
      basis of this disease (de novo resistance, relapsing-remitting and progressive).
      Drug resistant epilepsy, impacts negatively the quality of life and significantly
      increases the risk of premature death. From the neurobiological point of view,
      this medical condition is the result of the interaction of multiple variables
      related to the underlying disease, drug interactions and proper genetic aspects
      of each patient. Thanks to advances in pharmacogenetics and molecular biology
      research, currently some hypotheses may explain the cause of this condition and
      promote the study of new therapeutic options. Currently, overexpression of
      membrane transporters such as P-glycoprotein, appears to be one of the most
      important mechanisms in the development of drug resistant epilepsy. The objective
      of this review is to deepen the general aspects of this clinical condition,
      addressing the definition, epidemiology, differential diagnosis and the
      pathophysiological bases. 

PMID- 26204089
TI  - [VII Reunio Anual de les Societats Catalanes de Neurofisiologia Clinica i
      d'Electromiografia].

PMID- 26204090
TI  - [Hyperekplexia associated to precocious puberty].

PMID- 26204088
TI  - [GEITDAH consensus on conduct disorders in children and adolescents].
AB  - In this paper, the Special Interest Group on Attention Deficit Hyperactivity
      Disorder (GEITDAH, from its name in Spanish) presents a consensus reached by
      experts from all over Spain on conduct disorders in children and adolescents.
      Following the initial work by the team at the Pedopsychiatry Unit at the Quiron
      Teknon Hospital in Barcelona, agreements have been reached on a number of basic
      aspects that could be the starting point for future consensuses. A top priority
      aim of the work was also to update the criteria in the Diagnostic and statistical
      manual of mental disorders, fifth edition, for conduct disorders in children and
      adolescents, together with their comorbidity with attention deficit hyperactivity
      disorder. 

PMID- 26204091
TI  - [Progressive spastic paraparesis and static syringomyelia: Silver
      syndrome/SPG17].

PMID- 26204093
TI  - Vibrational lifetimes and friction in adsorbate motion determined from quasi
      elastic scattering.
AB  - The vibrational excitation of molecules adsorbed on a surface is typically probed
      by spectroscopic techniques such as infrared or Raman spectroscopy. In the
      present article we demonstrate an alternative method to determine vibrational
      lifetimes of adsorbate molecules using quasi-elastic helium atom scattering
      (QHAS). As a probe of diffusive motion of molecules on surfaces QHAS is well
      established. Here, we demonstrate that QHAS can also be used to probe the
      vibrational lifetime of a molecule in its adsorption well. Measurements of
      cyclopentadienyl, C5H5, on Cu(111) allow us to distinguish two substrate phonon
      modes as well as two molecular vibrational modes, perpendicular and parallel to
      the surface. We further find that the dephasing of the vibrational motion
      corresponds to the friction determined in previous diffusion measurements. 

PMID- 26204092
TI  - [Epicrania fugax as the initial presentation of migraine attacks].

PMID- 26204094
TI  - A Dual Receptor and Reporter for Multi-Modal Cell Surface Engineering.
AB  - The rapid development of new small molecule drugs, nanomaterials, and genetic
      tools to modulate cellular function through cell surface manipulation has
      revolutionized the diagnosis, study, and treatment of disorders in human health.
      Since the cell membrane is a selective gateway barrier that serves as the first
      line of defense/offense and communication to its environment, new approaches that
      molecularly engineer or tailor cell membrane surfaces would allow for a new era
      in therapeutic design, therapeutic delivery, complex coculture tissue
      construction, and in situ imaging probe tracking technologies. In order to
      develop the next generation of multimodal therapies, cell behavior studies, and
      biotechnologies that focus on cell membrane biology, new tools that intersect the
      fields of chemistry, biology, and engineering are required. Herein, we develop a
      liposome fusion and delivery strategy to present a novel dual receptor and
      reporter system at cell surfaces without the use of molecular biology or
      metabolic biosynthesis. The cell surface receptor is based on bio-orthogonal
      functional groups that can conjugate a range of ligands while simultaneously
      reporting the conjugation through the emission of fluorescence. We demonstrate
      this dual receptor and reporter system by conjugating and tracking various cell
      surface ligands for temporal control of cell fluorescent signaling, cell-cell
      interaction, and tissue assembly construction. 

PMID- 26204095
TI  - Fabrication and Short-Term in Vivo Performance of a Natural Elastic Lamina
      Polymeric Hybrid Vascular Graft.
AB  - Although significant advances have been made in the development of artificial
      vascular grafts, small-diameter grafts still suffer from excessive platelet
      activation, thrombus formation, smooth muscle cell intimal hyperplasia, and high
      occurrences of restenosis. Recent discoveries demonstrating the excellent blood
      contacting properties of the natural elastic lamina have raised the possibility
      that an acellular elastic lamina could effectively serve as a patent blood
      contacting surface in engineered vascular grafts. However, the elastic lamina
      alone lacks the requisite mechanical properties to function as a viable vascular
      graft. Here, we have screened a wide range of biodegradable and biostable medical
      grade polymers for their ability to adhere to the outer surface of the elastic
      lamina and allow cellular repopulation following engraftment in the rat abdominal
      aorta. We demonstrate a novel method for the fabrication of elastic lamina
      polymeric hybrid small-diameter vascular grafts and identify poly(ether urethane)
      (PEU 1074A) as ideal for this purpose. In vivo results demonstrate graft patency
      over 21 days, with low thrombus formation, mild inflammation, and the general
      absence of smooth muscle cell hyperplasia on the graft's luminal surface. The
      results provide a new direction for developing small-diameter vascular grafts
      that are mass-producible, shelf-stable, and universally compatible due to a lack
      of immune response and inhibit the in-graft restenosis response that is common to
      nonautologous materials. 

PMID- 26204096
TI  - Novel La3Fe(MoO4)6 phase: magnetic properties and ethanol reactivity.
AB  - Single crystals of a new oxide, La3Fe(MoO4)6, were grown from fluxes of oxide
      precursors, and a polycrystalline sample was also prepared by a standard solid
      state reaction. La3Fe(MoO4)6 crystallizes in the orthorhombic space group Pbca
      with unit cell parameters a = 19.3164(11), b = 10.4143(5) and c = 22.0594(12) A.
      This crystal structure exhibits a singular architectural type built on infinite
      chains of Fe(MoO4)4, each of them being surrounded by two isolated MoO4
      tetrahedra and three isolated La(3+) cations. Fe(3+) ions in La3Fe(MoO4)6 are
      antiferromagnetically ordered below TN = 6.6 K in chains and between chains, as
      refined from neutron diffraction data. Further the redox stability of this
      compound - pure powder - was checked using temperature-programmed X-ray
      diffraction under a controlled atmosphere; under air, we observed a reversible
      phase transition above 523 K. The same phenomenon was observed under a reductive
      atmosphere, followed by a destruction of the as-formed phase above 923 K owing to
      iron III to II reduction. Reactivity of ethanol was then evaluated to get
      insights into the redox properties of the material under working conditions.
      After 4 hours of reaction at 648 K, the ethanol conversion was 97% with a
      selectivity to acetaldehyde of ~60%, the other products being formaldehyde (~10%)
      and CO2 (~30%), underlining a better acetaldehyde selectivity than that of the La
      free conventional Fe2(MoO4)3 catalytic formulation. 

PMID- 26204097
TI  - Improved electrochemical performance of spinel LiMn(1.5)Ni(0.5)O4 through MgF2
      nano-coating.
AB  - A spinel LiMn1.5Ni0.5O4 (LMNO) cathode material synthesized by a sol-gel method
      is modified by MgF2 nano-coating via a wet coating strategy. The results of X-ray
      diffraction (XRD), Raman spectroscopy, field emission scanning electron
      microscopy (FESEM) and high resolution transmission electron microscopy (HRTEM)
      showed that the MgF2 nano-coating layers do not physically change the bulk
      structure of the pristine material. Compared with the pristine compound, the MgF2
      coated LMNO electrodes display enhanced cycling stabilities. Particularly, the 5
      wt% MgF2-coated LMNO demonstrates the best reversibility, with a capacity
      retention of 89.9% after 100 cycles, much higher than that of the pristine
      material, 69.3%. The dQ/dV analysis and apparent Li(+) diffusion coefficient
      calculation prove that the kinetic properties are enhanced after MgF2 surface
      modification, which partly explains the improved electrochemical performances.
      Electrochemical impedance spectroscopy (EIS) and Fourier transform infrared
      spectroscopy (FTIR) data confirm that the MgF2 coating layer helps in suppressing
      the fast growth of the solid electrolyte interface (SEI) film in repeated
      cycling, which effectively stabilizes the spinel structure. Additionally,
      differential scanning calorimetry (DSC) tests show that the MgF2 nano-coating
      layer also helps in enhancing the thermal stability of the LMNO cathode. 

PMID- 26204098
TI  - Ligand-Controlled Para-Selective C-H Arylation of Monosubstituted Arenes.
AB  - In a Pd-catalyzed double C-H activation reaction, a pyridine-type ligand is
      identified, for the first time, to enable a highly para-selective C-H arylation
      of monosubstituted arenes. Excellent para-selectivity is achieved with a variety
      of arenes containing alkyl, methoxyl, and halo substituents. 

PMID- 26204099
TI  - Cognitive control over visual food cue saliency is greater in reduced
      overweight/obese but not in weight relapsed women: An EEG study.
AB  - OBJECTIVE: Poor weight management may relate to a reduction in neurobehavioural
      control over food intake and heightened reactivity of the brain's neural reward
      pathways. Here we explore the neurophysiology of food-related visual cue
      processing in weight reduced and weight relapsed women by assessing differences
      in cortical arousal and attentional processing using a food-Stroop paradigm.
      METHODS: 51 women were recruited into 4 groups: reduced-weight participants (RED,
      n=14) compared to BMI matched low-weight controls (LW-CTL, n=18); and weight
      relapsed participants (REL, n=10) compared to BMI matched high-weight controls
      (HW-CTL, n=9). Eating behaviour and body image questionnaires were completed. Two
      Stroop tasks (one containing food images, the other containing neutral images)
      were completed with record of electroencephalography (EEG). RESULTS: Differences
      in cortical arousal were found in RED versus LW-CTL women, and were seen during
      food task execution only. Compared to their controls, RED women exhibited lower
      relative delta band power (p=0.01) and higher relative beta band power (p=0.01)
      over the right frontal cortex (F4). Within the RED group, delta band oscillations
      correlated positively with self-reported habitual fat intake and with body shape
      dissatisfaction. CONCLUSIONS: As compared to women matched for phenotype but with
      no history of weight reduction, reduced-overweight/obese women show increased
      neurobehavioural control over external food cues and the inhibition of reward
      orientated feeding responses. Insight into these self-regulatory mechanisms which
      attenuate food cue saliency may aid in the development of cognitive remediation
      therapies which facilitate long-term weight loss.

PMID- 26204101
TI  - Electron-vibration entanglement in the Born-Oppenheimer description of chemical
      reactions and spectroscopy.
AB  - Entanglement is sometimes regarded as the quintessential measure of the quantum
      nature of a system and its significance for the understanding of coupled
      electronic and vibrational motions in molecules has been conjectured. Previously,
      we considered the entanglement developed in a spatially localized diabatic basis
      representation of the electronic states, considering design rules for qubits in a
      low-temperature chemical quantum computer. We extend this to consider the
      entanglement developed during high-energy processes. We also consider the
      entanglement developed using adiabatic electronic basis, providing a novel way
      for interpreting effects of the breakdown of the Born-Oppenheimer (BO)
      approximation. We consider: (i) BO entanglement in the ground-state wavefunction
      relevant to equilibrium thermodynamics, (ii) BO entanglement associated with low
      energy wavefunctions relevant to infrared and tunneling spectroscopies, (iii) BO
      entanglement in high-energy eigenfunctions relevant to chemical reaction
      processes, and (iv) BO entanglement developed during reactive wavepacket
      dynamics. A two-state single-mode diabatic model descriptive of a wide range of
      chemical phenomena is used for this purpose. The entanglement developed by BO
      breakdown correlates simply with the diameter of the cusp introduced by the BO
      approximation, and a hierarchy appears between the various BO-breakdown
      correction terms, with the first-derivative correction being more important than
      the second-derivative correction which is more important than the diagonal
      correction. This simplicity is in contrast to the complexity of BO-breakdown
      effects on thermodynamic, spectroscopic, and kinetic properties. Further,
      processes poorly treated at the BO level that appear adequately treated using the
      Born-Huang adiabatic approximation are found to have properties that can only be
      described using a non-adiabatic description. For the entanglement developed
      between diabatic electronic states and the nuclear motion, qualitatively
      differently behavior is found compared to traditional properties of the density
      matrix and hence entanglement provides new information about system properties.
      For chemical reactions, this type of entanglement simply builds up as the
      transition-state region is crossed. It is robust to small changes in parameter
      values and is therefore more attractive for making quantum qubits than is the
      related fragile ground-state entanglement, provided that coherent motion at the
      transition state can be sustained. 

PMID- 26204100
TI  - Reply to the comment on "Sensitive marker bands for the detection of spin states
      of heme in surface-enhanced resonance Raman scattering spectra of metmyoglobin".
AB  - In our SERRS spectra of metmyoglobin by excitation at 514 nm, the peak at 1510
      cm(-1), which is assigned to the 6-coordinated heme in the low spin state, was
      observed by the addition of imidazole and NaN3. Thus, the SERRS likely originates
      not from the non-native 5-coordinated heme, which is in the high spin state. 

PMID- 26204102
TI  - Photo-control of DNA binding by an engrailed homeodomain-photoactive yellow
      protein hybrid.
AB  - A photo-controlled version of the engrailed homeodomain (zENG) was created by
      inserting the homeodomain into a surface loop of a circularly permuted version of
      the photoactive yellow protein (cPYP). The two proteins fold independently as
      judged by NMR and fluorescence denaturation measurements. In the dark, the
      affinity of the zENG domain for its cognate DNA is inhibited >100-fold compared
      to wild-type zENG. Blue-light irradiation of the hybrid protein leads to enhanced
      conformational dynamics of the cPYP portion and a two-fold enhancement of the DNA
      binding affinity of the zENG domain. These results suggest that insertion into a
      surface loop of cPYP can be a general approach for conferring an initial level of
      photo-control on a given target protein. Focussed mutation/selection strategies
      may then be used to enhance the degree of photo-control. 

PMID- 26204103
TI  - Synthesis and Electronic Structure of Ru2(Xap)4(Y-gem-DEE) Type Compounds: Effect
      of Cross-Conjugation.
AB  - Reported in this Article are the preparation and characterization of a series of
      new Ru2(II,III) compounds bearing one cross-conjugated sigma-geminal
      diethynylethene ligand (gem-DEE), namely, Ru2(Xap)4(Y-gem-DEE) (Xap = N,N'
      anilinopyridinate (ap) or 2-(3,5-dimethoxy)anilinopyridinate (DiMeOap), and Y =
      Si(i)Pr3 (1) or H (2)) and [Ru2(ap)4]2(MU-gem-DEE) (3). Compounds 1-3 were
      characterized by spectroscopic and voltammetric techniques as well as the single
      crystal X-ray diffraction study of 2a. The X-ray structural data of 2a and the
      spectroscopic/voltammetric data of compounds 1 and 2 indicate that the gem-DEE
      ligands are similar to simple alkynyls in their effects on the molecular and
      electronic structures of the Ru2(Xap)4 moiety. Similar to the previously studied
      [Ru2(ap)4]2(MU-C2n) type compounds, dimer 3 exhibits pairwise 1e(-) oxidations
      and reductions, albeit the potential splits within the pair (DeltaE1/2) are
      significantly smaller than those of [Ru2(ap)4]2(MU-C4). The electronic absorption
      spectra of the reduced and oxidized derivatives of 1a and 3 were determined using
      spectroelectrochemistry methods. No discernible intervalence charge transfer
      transition (IVCT) was detected in the near-IR spectrum for either 3(-) or 3(+),
      suggesting that the Ru2-Ru2 coupling in these mixed-valence states is weak. DFT
      calculations on a model compound of 3 yielded six singly occupied molecular
      orbitals (SOMOs), which have Ru2 contributions similar to those previously
      calculated for the [Ru2(ap)4]2(MU-C2n) type compounds. Among six SOMOs, SOMO-2 is
      the only one containing substantial dpi-pi(gem-DEE) character across the entire
      Ru2-MU-gem-DEE-Ru2 linkage, which explains the weakened Ru2-Ru2 coupling. 

PMID- 26204104
TI  - Shape effect in cellular uptake of PEGylated nanoparticles: comparison between
      sphere, rod, cube and disk.
AB  - The size, shape, surface property and material composition of polymer-coated
      nanoparticles (NPs) are four important parameters in designing efficient NP-based
      carriers for targeted drug delivery. However, due to the complex interplay
      between size, shape and surface property, most studies lead to ambiguous
      descriptions of the relevance of shape. To clarify its influence on the cellular
      uptake of PEGylated NPs, large scale molecular simulations have been performed to
      study differently shaped convex NPs, such as sphere, rod, cube and disk.
      Comparing systems with identical NP surface area, ligand-receptor interaction
      strength, and grafting density of the polyethylene glycol, we find that the
      spherical NPs exhibit the fastest internalization rate, followed by the cubic
      NPs, then rod- and disk-like NPs. The spherical NPs thus demonstrate the highest
      uptake among these differently shaped NPs. Based on a detailed free energy
      analysis, the NP shape effect is found to be mainly induced by the different
      membrane bending energies during endocytosis. The spherical NPs need to overcome
      a minimal membrane bending energy barrier, compared with the non-spherical
      counterparts, while the internalization of disk-like NPs involves a strong
      membrane deformation, responsible for a large free energy barrier. Besides, the
      free energy change per tethered chain is about a single kBT regardless of NP
      shape, as revealed by our self-consistent field theory calculations, where kB and
      T denote Boltzmann constant and temperature, respectively. Thus, the NP shape
      only plays the secondary role in the free energy change of grafted PEG polymers
      during internalization. We also find that star-shaped NPs can be quickly wrapped
      by the cell membrane, similar to their spherical counterparts, indicating star
      shaped NPs can be used for drug delivery with high efficacy. Our findings seem to
      provide useful guidance in the molecular design of PEGylated NPs for controllable
      cellular uptake and help establish quantitatively rules in designing NP-based
      vectors for targeted drug delivery. 

PMID- 26204105
TI  - The Accuracy of ADC Measurements in Liver Is Improved by a Tailored and
      Computationally Efficient Local-Rigid Registration Algorithm.
AB  - This study describes post-processing methodologies to reduce the effects of
      physiological motion in measurements of apparent diffusion coefficient (ADC) in
      the liver. The aims of the study are to improve the accuracy of ADC measurements
      in liver disease to support quantitative clinical characterisation and reduce the
      number of patients required for sequential studies of disease progression and
      therapeutic effects. Two motion correction methods are compared, one based on non
      rigid registration (NRA) using freely available open source algorithms and the
      other a local-rigid registration (LRA) specifically designed for use with
      diffusion weighted magnetic resonance (DW-MR) data. Performance of these methods
      is evaluated using metrics computed from regional ADC histograms on abdominal
      image slices from healthy volunteers. While the non-rigid registration method has
      the advantages of being applicable on the whole volume and in a fully automatic
      fashion, the local-rigid registration method is faster while maintaining the
      integrity of the biological structures essential for analysis of tissue
      heterogeneity. Our findings also indicate that the averaging commonly applied to
      DW-MR images as part of the acquisition protocol should be avoided if possible. 

PMID- 26204106
TI  - Physician Underestimation of the Risk of Gastrointestinal Stromal Tumor
      Recurrence After Resection.
AB  - IMPORTANCE: Patients with resectable gastrointestinal stromal tumors (GISTs)
      might not receive the recommended duration of adjuvant therapy if their risk of
      recurrence is underestimated, which can have an impact on their recurrence-free
      survival (RFS). OBJECTIVE: To determine the extent of physician underestimation
      of risk of recurrence after complete primary GIST resection, the impact of
      underestimation on planned adjuvant treatment duration, and the association among
      high-risk patients of planned adjuvant treatment duration and RFS. DESIGN,
      SETTING, AND PARTICIPANTS: This was a retrospective observational medical record
      review reported by participating oncologists in 2013. US patients with complete
      primary GIST resection after 2010 were grouped as underestimated or not if their
      oncologists' charted risk assessments were lower than assessments based on the
      Revised National Institutes of Health Consensus Criteria or not. Patients were
      followed by general community oncologists until death or the end of follow-up.
      MAIN OUTCOMES AND MEASURES: Fisher exact tests compared planned adjuvant
      treatment duration between groups. Cox proportional-hazards models estimated the
      impact of planned adjuvant treatment duration on RFS. RESULTS: A total of 109
      oncologists reported information on 506 patients with GIST after primary
      resection (65.8% were high-risk and 8.7% were intermediate-risk). Physicians
      underestimated risk for 190 patients (37.5%); 30.1% of tumors with an
      intermediate-level mitotic count (6-10 per 50 high-powered fields) and an
      intermediate tumor size (6-10 cm) were correctly recognized as high-risk, as were
      7.5% of nongastric tumors with an intermediate-level mitotic count and a tumor
      size of 2 to 5 cm. A smaller proportion of high-risk patients in the
      underestimated vs not-underestimated groups had at least 3 years of planned
      adjuvant therapy (36.1% vs 65.9%; P < .001). Planned adjuvant treatment of at
      least 3 years vs less than 3 years among high-risk patients conferred a lower
      hazard of recurrence and/or death (adjusted hazard ratio, 0.29; P < .001; 95% CI,
      0.14-0.59). CONCLUSIONS AND RELEVANCE: Overall, physicians tended to
      underestimate the risk of recurrence for many patients with GIST, especially for
      patients with tumors of intermediate size, intermediate-level mitotic count, and
      nongastric location, which had an impact on planned adjuvant therapy duration.
      Patients with at least 3 years of planned adjuvant treatment had longer RFS.
      Improved education on postresection risk assessment and risk reduction is needed.

PMID- 26204107
TI  - Pulseless Oximetry: A Preliminary Evaluation.
AB  - BACKGROUND: Pulse oximetry fails when pulsations are weak or absent, common in
      patients with continuous flow left ventricular assist devices (LVADs). We
      developed a method to measure arterial oxygenation (Sao2) noninvasively in
      pulseless patients with LVADs. METHODS: The technique involves 5- to 10-s
      occlusions of radial and ulnar arteries on one hand. A fingertip is
      transilluminated alternately with light-emitting diodes emitting 660 nm (red) and
      905 nm (infrared). During the approximately 1 s after release of occlusion,
      changing attenuance of each wavelength is measured and their red/infrared
      arterial blood attenuance ratio (R/IR) calculated. We studied five normal
      subjects breathing hyperoxic, normoxic, or hypoxic gas mixtures to establish a
      calibration curve, using standard pulse oximetry as the gold standard. We also
      studied seven pulseless patients with LVADs (two studied twice) at clinically
      determined oxygenation. RESULTS: Normal subject data showed close correlation of
      oxygen saturation by pulse oximetry (Spo2) with R/IR, (Spo2 = 111 - [26.7 *
      R/IR]; R2 = 0.975). For patients with LVADs, predicted Sao2 (from the calibration
      curve) tended to underestimate measured Sao2 (from arterial blood) by a
      clinically insignificant 1.1 +/- 1.6 percentage points (mean +/- SD), maximum 3.4
      percentage points. CONCLUSIONS: Preliminary results in a small number of patients
      demonstrate that pulseless oximetry can be used to estimate arterial saturation
      with acceptable accuracy. A noninvasive oximeter that does not rely on pulsatile
      flow would be a valuable advance in assessing oxygenation in patients with LVADs,
      for whom the only current option is arterial puncture, which is painful, risks
      arterial injury, and only provides a snapshot evaluation of oxygenation.

PMID- 26204108
TI  - Turning Up the Heat: Inflammasome Activation by Fungal Pathogens.

PMID- 26204110
TI  - Bribe and Punishment: An Evolutionary Game-Theoretic Analysis of Bribery.
AB  - Harassment bribes, paid by citizens to corrupt officers for services the former
      are legally entitled to, constitute one of the most widespread forms of
      corruption in many countries. Nation states have adopted different policies to
      address this form of corruption. While some countries make both the bribe giver
      and the bribe taker equally liable for the crime, others impose a larger penalty
      on corrupt officers. We examine the consequences of asymmetric and symmetric
      penalties by developing deterministic and stochastic evolutionary game-theoretic
      models of bribery. We find that the asymmetric penalty scheme can lead to a
      reduction in incidents of bribery. However, the extent of reduction depends on
      how the players update their strategies over time. If the interacting members
      change their strategies with a probability proportional to the payoff of the
      alternative strategy option, the reduction in incidents of bribery is less
      pronounced. Our results indicate that changing from a symmetric to an asymmetric
      penalty scheme may not suffice in achieving significant reductions in incidents
      of harassment bribery. 

PMID- 26204109
TI  - Effects of azithromycin on gene expression profiles of proinflammatory and anti
      inflammatory mediators in the eyelid margin and conjunctiva of patients with
      meibomian gland disease.
AB  - IMPORTANCE: Topical application of azithromycin suppresses expression of
      proinflammatory mediators while restoring transforming growth factor beta1 (TGF
      beta1) levels as evaluated by eyelid margin and conjunctival impression cytology.
      OBJECTIVE: To explore the effects of azithromycin therapy on expression of
      proinflammatory and anti-inflammatory mediators in meibomian gland disease (MGD).
      DESIGN, SETTING, AND PARTICIPANTS: Case-control study performed in a clinic
      setting from August 17, 2010, to December 31, 2010. Sixteen patients with
      posterior blepharitis and conjunctival inflammation due to MGD were treated with
      azithromycin, 1%, drops for 4 weeks. Impression cytology of the lower eyelid
      margin and tarsal conjunctiva to measure cytokine expression by quantitative real
      time polymerase chain reaction as well as tear collection to measure matrix
      metalloproteinase 9 (MMP-9) activity were performed once in 8 asymptomatic
      healthy control participants and 5 times in the 16 symptomatic patients (every 2
      weeks for 8 weeks), before, during, and after azithromycin treatment. EXPOSURE:
      Azithromycin, 1%, drops for 4 weeks. MAIN OUTCOMES AND MEASURES: Cytokine
      expression in the eyelid margin and conjunctiva, and MMP-9 activity in tears.
      RESULTS: Compared with a 1-time measurement of 8 healthy participants, among 16
      symptomatic patients, the mean (SD; 95% CI) fold change of expression of
      proinflammatory mediators interleukin 1beta (IL-1beta), IL-8, and MMP-9 increased
      to 13.26 (4.33; 11.14-15.38; P < .001), 9.38 (3.37; 7.73-11.03; P < .001), and
      13.49 (4.92; 11.08-15.90; P < .001), respectively, in conjunctival cells and to
      11.75 (3.96; 9.81-13.69; P < .001), 9.31 (3.28; 7.70-10.92; P < .001), and 11.52
      (3.50; 9.81-13.24; P < .001), respectively, in the eyelid margin of patients with
      MGD. In contrast, the mean (SD; 96% CI) fold change of expression of TGF-beta1
      messenger RNA (mRNA) decreased to 0.58 (0.25; 0.46-0.70; P = .02) and 0.63 (0.14;
      0.56-0.70; P = .02) in conjunctival and eyelid margin cells, respectively, of
      patients with MGD. Azithromycin, 1%, caused a change in the expression pattern of
      these mediators toward normal levels during 4 weeks of treatment. Levels of IL
      1beta, IL-8, and MMP-9 mRNA remained suppressed, although they rebounded toward
      pretreatment values 4 weeks after azithromycin withdrawal. Expression of TGF
      beta1 increased during treatment and remained at levels similar to the healthy
      controls after drug withdrawal. Change in tear MMP-9 activity was similar to the
      pattern of MMP-9 transcripts. CONCLUSIONS AND RELEVANCE: While the study did not
      control for potential confounding factors over time independent of the
      intervention that may have contributed to the results, topical azithromycin
      suppressed expression of proinflammatory mediators and increased expression of
      TGF-beta1 to normal levels. Increased TGF-beta1 expression may contribute to the
      anti-inflammatory activity of azithromycin in MGD.

PMID- 26204111
TI  - The Potential Impact of Risk-Based Screening Mammography in Women 40-49 Years
      Old.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of very
      strong family history and extremely dense tissue in women 40-49 years old with
      breast cancer detected on screening mammography. MATERIALS AND METHODS: All
      cancers detected by screening mammography at our institution between January 1997
      and November 2012 in 40- to 49-year-old women were retrospectively identified.
      Those with a personal history of breast cancer were excluded. Family history,
      breast density, type of malignancy, hormone receptor status, and lymph node
      status were recorded. RESULTS: One hundred thirty-six cases of breast cancer were
      identified on screening mammography in 40- to 49-year-old women; 50% were
      invasive cancers, and 50%, ductal carcinoma in situ. Very strong family history
      was absent in 88%, and extremely dense breast tissue was absent in 86%. Seventy
      six percent of patients had neither very strong family history nor extremely
      dense breasts, including 79% of the cases of invasive cancers, of which 25% had
      axillary nodal involvement and 89% were estrogen receptor positive. CONCLUSION:
      Very strong family history and extremely dense breast tissue were absent in most
      40- to 49-year-old women with breast cancer detected at screening mammography.
      These cancers were frequently invasive (often with nodal metastases) and
      treatable (hormone receptor positive). Reducing the number of women to be
      screened in this age group by using this risk-based approach would reduce the
      number of screen-detected cancers by more than 75%, thereby precluding the
      benefit of mortality reduction. Even using a risk-based strategy with an expanded
      definition of high risk that included any first-degree family history, extremely
      dense tissue, or both, 66% of malignancies would still be missed.

PMID- 26204112
TI  - Renal Ablation Techniques: State of the Art.
AB  - OBJECTIVE: The purpose of this article is to describe the indications for and
      approach to image-guided percutaneous ablation of renal tumors. CONCLUSION: Image
      guided ablation techniques have become accepted treatment of patients with small
      renal tumors, a viable alternative to partial nephrectomy.

PMID- 26204113
TI  - Evaluation of Perihilar Biliary Strictures: Does DWI Provide Additional Value to
      Conventional MRI?
AB  - OBJECTIVE: The purpose of this study is to evaluate whether DWI provides
      additional value to conventional MRI with MRCP (MRI-MRCP) in the characterization
      of perihilar biliary strictures and in the evaluation of the longitudinal extent
      of perihilar cholangiocarcinomas. MATERIALS AND METHODS: One hundred fourteen
      patients with perihilar strictures (81 malignant and 33 benign) underwent
      gadobutrol-enhanced MRI-MRCP and DWI using 10 b values (0-1000 s/mm(2)). Two
      readers independently reviewed a conventional set of MRI-MRCP images and a
      combined set of MRI-MRCP and DW images and scored the likelihoods of malignancy
      for perihilar strictures and involvement of the bilateral secondary confluence in
      malignant cases on a 5-point scale. The diagnostic performance of the two imaging
      sets was compared using ROC analysis. RESULTS: In the characterization of 114
      perihilar strictures, the addition of DWI showed no statistically significant
      improvement in diagnostic performance (reader 1, area under the ROC curve (Az) =
      0.947 vs 0.923; reader 2, Az = 0.930 vs 0.905; all p > 0.05) with an
      interobserver agreement of kappa = 0.763-0.818. In determining bilateral
      secondary confluence involvement for the 81 surgically confirmed malignant
      strictures, the conventional and combined sets showed no statistically
      significant difference in diagnostic performance (reader 1, Az = 0.820 vs 0.868;
      reader 2, Az = 0.826 vs 0.829; all p > 0.05), with kappa = 0.564-0.588.
      CONCLUSION: The addition of DWI to conventional MRI-MRCP did not improve
      diagnostic performance in the characterization of perihilar strictures or in
      determining whether the bilateral secondary biliary confluence was involved in
      perihilar cholangiocarcinomas.

PMID- 26204114
TI  - Effects of Performance Feedback Reports on Adherence to Evidence-Based Guidelines
      in Use of CT for Evaluation of Pulmonary Embolism in the Emergency Department: A
      Randomized Trial.
AB  - OBJECTIVE: The purpose of this study was to assess whether implementing emergency
      department (ED) physician performance feedback reports improves adherence to
      evidence-based guidelines for use of CT for evaluation of pulmonary embolism (PE)
      beyond that achieved with clinical decision support (CDS) alone. SUBJECTS AND
      METHODS: This prospective randomized controlled trial was conducted from January
      1, 2012, to December 31, 2013, at an urban level 1 adult trauma center ED.
      Attending physicians were stratified into quartiles by use of CT for evaluation
      of PE in 2012 and were randomized to receive quarterly feedback reporting or not,
      beginning January 2013. Reports consisted of individual and anonymized group data
      on guideline adherence (using the Wells criteria), use of CT for PE (number of CT
      examinations for PE per 1000 patients), and yield (percentage of CT examinations
      for PE with positive findings). We compared guideline adherence (primary outcome)
      and use and yield (secondary outcomes) of CT for PE between the control and
      intervention groups in 2013 and with historical imaging data from 2012. RESULTS:
      Of 109,793 ED patients during the control and intervention periods, 2167 (2.0%)
      underwent CT for evaluation of PE. In the control group, guideline adherence
      remained unchanged between 2012 (78.8% [476/604]) and 2013 (77.2% [421/545]) (p =
      0.5); in the intervention group, guideline adherence increased 8.8% after
      feedback report implementation, from 78.3% (426/544) to 85.2% (404/474) (p <
      0.05). Use and yield were unchanged in both groups. CONCLUSION: Implementation of
      quarterly feedback reporting resulted in a modest but significant increase in
      adherence to evidence-based guidelines for use of CT for evaluation of PE in ED
      patients, enhancing the impact of CDS alone. These results suggest potentially
      synergistic effects of traditional performance improvement tools with CDS to
      improve guideline adherence.

PMID- 26204116
TI  - The Clinical Significance of Dark Cartilage Lesions Identified on MRI.
AB  - OBJECTIVE: The purpose of this study was to determine the clinical significance
      of foci of low signal intensity in morphologically normal cartilage. MATERIALS
      AND METHODS: This retrospective study included 887 patients who underwent 898
      knee MRI examinations performed within 6 months of arthroscopic knee surgery. A
      musculoskeletal radiologist reviewed all MRI examinations for the presence of
      foci of low signal in cartilage where there was no visible morphologic
      abnormality, referred to as "dark cartilage lesions." The surgical reports of all
      patients were reviewed for the presence of cartilage degeneration at arthroscopy.
      Logistic regression was used to model the probability of dark cartilage lesions
      corresponding to cartilage degeneration at arthroscopy as a function of patient
      age. RESULTS: In the 5388 articular surfaces assessed on MRI, 142 dark cartilage
      lesions were identified. The proportion of dark cartilage lesions corresponding
      to cartilage degeneration at arthroscopy was 52.0% (13 of 25) in the patella,
      57.1% (28 of 49) in the trochlea, 90.9% (10 of 11) in the medial femoral condyle,
      50.0% (two of four) in the lateral femoral condyle, 80.0% (four of five) in the
      medial tibial plateau, and 70.8% (34 of 48) in the lateral tibial plateau. There
      was a direct correlation (R(2) = 0.89) between patient age and the likelihood
      that a dark cartilage lesion would correspond to cartilage degeneration at
      arthroscopy. CONCLUSION: Dark cartilage lesions may be found on every articular
      surface of the knee joint and may be a sign of otherwise occult cartilage
      degeneration.

PMID- 26204115
TI  - Whole-Body Metabolic Tumor Volume, as Determined by (18)F-FDG PET/CT, as a
      Prognostic Factor of Outcome for Patients With Breast Cancer Who Have Distant
      Metastasis.
AB  - OBJECTIVE: This study was performed to evaluate the prognostic relevance of PET
      parameters measured by (18)F-FDG PET/CT in patients with invasive ductal
      carcinoma of the breast (IDC) who had distant metastasis at the time of initial
      diagnosis. MATERIALS AND METHODS: Forty women with IDC who had distant metastasis
      at the time of initial diagnosis and who underwent FDG PET/CT before receiving
      treatment were enrolled in the study. Clinicopathologic parameters and metabolic
      PET parameters, including the maximum standardized uptake value (SUVmax) of the
      primary tumor (pSUVmax), the SUVmax of the axillary lymph node (nSUVmax), the
      highest SUVmax of whole malignant lesions (wSUVmax), the whole-body (WB)
      metabolic tumor volume (MTV), and WB total lesion glycolysis (TLG), were analyzed
      to determine their usefulness in predicting overall survival (OS). Univariate and
      multivariate analyses were performed with the use of Kaplan-Meier and Cox
      proportional hazards models. RESULTS: Twenty-one of the 40 patients (52.5%) died
      during follow-up (mean follow-up, 36.4 months; range, 0.8-71.4 months).
      Nonsurvivors had a statistically significantly higher mean (+/- SD) WB MTV than
      did survivors (424.0 +/- 683.9 vs 92.1 +/- 96.3 cm(3); p = 0.0430). T category,
      performance of palliative surgery, presence of visceral metastasis, wSUVmax, WB
      MTV, and WB TLG were identified by univariate analysis as prognostic factors for
      OS, whereas age, N category, hormone receptor status, status, triple-negative
      breast cancer status (defined as a tumor for which estrogen receptor,
      progesterone receptor, and ERBB2 statuses were all negative), pSUVmax, and
      nSUVmax were not. Multivariate analysis revealed that only WB MTV independently
      predicted OS (hazard ratio, 4.10; 95% CI, 1.17-14.31; p = 0.0280). CONCLUSION:
      The WB MTV value, as determined by FDG PET/CT performed before treatment, was
      found to be an independent prognostic factor for OS in patients with IDC who had
      distant metastasis at the time of initial diagnosis.

PMID- 26204117
TI  - UK Doubles Its "World-Leading" Research in Life Sciences and Medicine in Six
      Years: Testing the Claim?
AB  - BACKGROUND: The UK, like some other countries, carries out a periodic review of
      research quality in universities and the most recent Research Excellence
      Framework (REF) reported a doubling (103% increase) in its "world leading" or so
      called "4*" research outputs in the areas of life sciences and medicine between
      2008 and 2014. This is a remarkable improvement in six years and if validated
      internationally could have profound implications for health sciences. METHODS: We
      compared the reported changes in 4* quality to bibliometric measures of quality
      for the 56,639 articles submitted to the RAE 2008 and the 50,044 articles
      submitted to the REF 2014 to Panel A, which assesses the life sciences, including
      medicine. FINDINGS: UK research submitted to the RAE and REF was of better
      quality than worldwide research on average. While we found evidence for some
      increase in the quality of top UK research articles, a 10-25% increase in the top
      10%ile papers, depending upon the metrics used, we could not find evidence to
      support a 103% increase in quality. Instead we found that as compared to the RAE,
      the REF results implied a lower citation %ile threshold for declaring a 4*.
      INTERPRETATION: There is a wide discrepancy between bibliometric indices and peer
      review panel judgements between the RAE 2008 and REF 2014. It is possible that
      the changes in the funding regime between 2008 and 2014 that significantly
      increased the financial premium for 4* articles may have influenced research
      quality evaluation. For the advancement of science and health, evaluation of
      research quality requires consistency and validity - the discrepancy noted here
      calls for a closer examination of mass peer-review methods like the REF.

PMID- 26204118
TI  - Comparison of the Mitochondrial Genomes and Steady State Transcriptomes of Two
      Strains of the Trypanosomatid Parasite, Leishmania tarentolae.
AB  - U-insertion/deletion RNA editing is a post-transcriptional mitochondrial RNA
      modification phenomenon required for viability of trypanosomatid parasites. Small
      guide RNAs encoded mainly by the thousands of catenated minicircles contain the
      information for this editing. We analyzed by NGS technology the mitochondrial
      genomes and transcriptomes of two strains, the old lab UC strain and the recently
      isolated LEM125 strain. PacBio sequencing provided complete minicircle sequences
      which avoided the assembly problem of short reads caused by the conserved
      regions. Minicircles were identified by a characteristic size, the presence of
      three short conserved sequences, a region of inherently bent DNA and the presence
      of single gRNA genes at a fairly defined location. The LEM125 strain contained
      over 114 minicircles encoding different gRNAs and the UC strain only ~24
      minicircles. Some LEM125 minicircles contained no identifiable gRNAs. Approximate
      copy numbers of the different minicircle classes in the network were determined
      by the number of PacBio CCS reads that assembled to each class. Mitochondrial RNA
      libraries from both strains were mapped against the minicircle and maxicircle
      sequences. Small RNA reads mapped to the putative gRNA genes but also to multiple
      regions outside the genes on both strands and large RNA reads mapped in many
      cases over almost the entire minicircle on both strands. These data suggest that
      minicircle transcription is complete and bidirectional, with 3' processing
      yielding the mature gRNAs. Steady state RNAs in varying abundances are derived
      from all maxicircle genes, including portions of the repetitive divergent region.
      The relative extents of editing in both strains correlated with the presence of a
      cascade of cognate gRNAs. These data should provide the foundation for a deeper
      understanding of this dynamic genetic system as well as the evolutionary
      variation of editing in different strains. 

PMID- 26204119
TI  - A Novel Quality Measure and Correction Procedure for the Annotation of Microbial
      Translation Initiation Sites.
AB  - The identification of translation initiation sites (TISs) constitutes an
      important aspect of sequence-based genome analysis. An erroneous TIS annotation
      can impair the identification of regulatory elements and N-terminal signal
      peptides, and also may flaw the determination of descent, for any particular
      gene. We have formulated a reference-free method to score the TIS annotation
      quality. The method is based on a comparison of the observed and expected
      distribution of all TISs in a particular genome given prior gene-calling. We have
      assessed the TIS annotations for all available NCBI RefSeq microbial genomes and
      found that approximately 87% is of appropriate quality, whereas 13% needs
      substantial improvement. We have analyzed a number of factors that could affect
      TIS annotation quality such as GC-content, taxonomy, the fraction of genes with a
      Shine-Dalgarno sequence and the year of publication. The analysis showed that
      only the first factor has a clear effect. We have then formulated a
      straightforward Principle Component Analysis-based TIS identification strategy to
      self-organize and score potential TISs. The strategy is independent of reference
      data and a priori calculations. A representative set of 277 genomes was subjected
      to the analysis and we found a clear increase in TIS annotation quality for the
      genomes with a low quality score. The PCA-based annotation was also compared with
      annotation with the current tool of reference, Prodigal. The comparison for the
      model genome of Escherichia coli K12 showed that both methods supplement each
      other and that prediction agreement can be used as an indicator of a correct TIS
      annotation. Importantly, the data suggest that the addition of a PCA-based
      strategy to a Prodigal prediction can be used to 'flag' TIS annotations for re
      evaluation and in addition can be used to evaluate a given annotation in case a
      Prodigal annotation is lacking. 

PMID- 26204120
TI  - Human Leukocyte Antigen DQB1 (HLA-DQB1) Polymorphisms and the Risk for Guillain
      Barre Syndrome: A Systematic Review and Meta-Analysis.
AB  - Guillain-Barre syndrome (GBS) is an autoimmune disorder of the peripheral nervous
      system. There is no consensus regarding reported associations between human
      leukocyte antigen DQB1 (HLA-DQB1) polymorphisms and the risk for developing GBS.
      Here, we evaluated possible associations between HLA-DQB1 polymorphisms and the
      risk for GBS using a meta-analysis. We searched PubMed for case-control genetic
      association studies for HLA-DQB1 polymorphisms (*020x, *030x, *040x, *050x, and
      *060x) and the risk for GBS. Fixed-effect meta-analytical methods were used for
      the outcome measure and subgroup analyses. Estimated odds ratios (ORs) and 95%
      confidence intervals (CIs) were used to investigate the associations between HLA
      DQB1 polymorphisms and the risk for GBS. Nine case-control studies involving 780
      cases of GBS and 1353 controls were identified in the current study. The meta
      analysis demonstrated no significant associations between HLA-DQB1 polymorphisms
      and the risk for GBS in Asian and Caucasian populations. There were two
      associations that approached significance: HLA-DQB1*030x in Asian patients (P =
      0.07; OR: 0.76, 95% CI: 0.57-1.03) and HLA-DQB1*060x in all patients (P = 0.08;
      OR: 1.48, 95% CI: 0.96-2.29). Additional studies with larger sample sizes are
      required to establish a definitive assessment of the contribution of HLA-DQB1
      polymorphisms to GBS risk. 

PMID- 26204121
TI  - Can They See It? The Functional Field of View Is Narrower in Individuals with
      Autism Spectrum Disorder.
AB  - Although social cognitive deficits have long been thought to underlie the
      characteristic and pervasive difficulties with social interaction observed in
      individuals with autism spectrum disorder (ASD), several recent behavioral and
      neuroimaging studies have indicated that visual perceptual impairments might also
      play a role. People with ASD show a robust bias towards detailed information at
      the expense of global information, although the mechanisms that underlie this
      phenomenon remain elusive. To address this issue, we investigated the functional
      field of view in a group of high-functioning children with autism (n = 13) and a
      paired non-ASD group (n = 13). Our results indicate that the ability to correctly
      detect and identify stimuli sharply decreases with greater eccentricity from the
      fovea in people with ASD. Accordingly, a probe analysis revealed that the
      functional field of view in the ASD group was only about 6.62 degrees  of retinal
      eccentricity, compared with 8.57 degrees  in typically developing children. Thus,
      children with ASD appear to have a narrower functional field of view. These
      results challenge the conventional hypothesis that the deficit in global
      processing in individuals with ASD is solely due to weak central coherence.
      Alternatively, our data suggest that a narrower functional field of view may also
      contribute to this bias. 

PMID- 26204122
TI  - Risk Stratification of Patients With Acute Symptomatic Pulmonary Embolism Based
      on Presence or Absence of Lower Extremity DVT: Systematic Review and Meta
      analysis.
AB  - BACKGROUND: For patients diagnosed with acute pulmonary embolism (PE), the
      prognostic significance of concomitant DVT lacks clarity. METHODS: We performed a
      meta-analysis of studies that enrolled patients with acute PE to assess the
      prognostic value of concomitant DVT for the primary outcome of 30-day all-cause
      mortality and the secondary outcome of 90-day PE-related adverse events. We
      conducted unrestricted searches of PubMed and Embase from 1980 through September
      30, 2014, and used the terms "deep vein thrombosis," "pulmonary embolism," and
      "prognos*." We used a random-effects model to pool study results, Begg rank
      correlation method to evaluate for publication bias, and I(2) testing to assess
      for heterogeneity. RESULTS: The meta-analysis included a total of nine studies
      (10 cohorts, as one study had two cohorts) with 8,859 patients. Of the seven
      cohorts with 7,868 participants who had PE and provided results on the primary
      outcome, 4,379 (56%) had concomitant DVT; 272 of 4,379 (6.2%) patients with
      concomitant DVT died 30 days after the diagnosis of PE compared with 133 of 3,489
      (3.8%) without DVT. Concomitant DVT had a significant association with 30-day all
      cause mortality in all patients (seven cohorts; OR, 1.9; 95% CI, 1.5-2.4; I(2) =
      0%). Concomitant DVT was not significantly associated with 90-day PE-related
      adverse outcomes (five cohorts; OR, 1.6; 95% CI, 0.8-3.4; I(2) = 75%).
      CONCLUSIONS: In patients diagnosed with acute symptomatic PE, concomitant DVT was
      significantly associated with an increased risk of death within 30 days of PE
      diagnosis.

PMID- 26204123
TI  - When in Doubt, Breastfeeding Is the Default.

PMID- 26204124
TI  - ABM Clinical Protocol #18: Use of Antidepressants in Breastfeeding Mothers.
AB  - A central goal of The Academy of Breastfeeding Medicine is the development of
      clinical protocols for managing common medical problems that may impact
      breastfeeding success. These protocols serve only as guidelines for the care of
      breastfeeding mothers and infants and do not delineate an exclusive course of
      treatment or serve as standards of medical care. Variations in treatment may be
      appropriate according to the needs of an individual patient. 

PMID- 26204125
TI  - Daily Breastmilk Volume in Mothers of Very Low Birth Weight Neonates: A Repeated
      Measures Randomized Trial of Hand Expression Versus Electric Breast Pump
      Expression.
AB  - BACKGROUND: There are no randomized trials comparing early exclusive hand
      expression (HE) with early exclusive electric pump expression (electric
      expression [EE]) for milk removal in mothers of very low birth weight (VLBW)
      infants. SUBJECTS AND METHODS: Mothers of VLBW infants were randomized to
      exclusively HE or EE for the first 7 days postpartum. Daily volumes of milk were
      compared between groups for the first 28 days, adjusting for repeated measures.
      RESULTS: The HE (n=12) and the EE (n=14) groups did not differ with respect to
      age, parity, single versus multiple gestation, or number of expression sessions
      per day. There were 728 values for daily milk volumes in the first 28 days,
      including 105 HE and 623 EE. Mothers using exclusive HE had significantly
      (p<0.05) less cumulative daily milk production throughout the first 7 days
      postpartum compared with exclusive EE. Mean cumulative milk production among
      mothers using HE in the first postpartum week remained approximately half that of
      those using the electric pump throughout the first 28 days, without evident catch
      up. In multivariable analysis, each postpartum day was associated with an
      adjusted increase of 50 mL of human milk/day during the first 7 days postpartum
      and an increase of 13 mL/day between postpartum Days 8 and 28. After adjusting
      for repeated measures, number of expression sessions per day, and postpartum day,
      EE was associated with an advantage in milk production of 119 mL/day during the
      first 28 postpartum days compared with HE. CONCLUSIONS: Compared with mothers
      using EE, mothers using HE had significantly less cumulative daily milk
      production during the first 7 days postpartum. This trend continued after the
      intervention had been discontinued, and the great majority of expressions in both
      groups were with EE. Further research to confirm and expand these findings is
      warranted.

PMID- 26204126
TI  - Comparison of combined hormonal vaginal ring with ultralow-dose combined oral
      contraceptive pills in the management of heavy menstrual bleeding: A pilot study.
AB  - The aim of this study was to compare combined hormonal vaginal ring with ultralow
      dose combined oral contraceptive (COC) pills in management of heavy menstrual
      bleeding (HMB). Fifty patients were randomised into Group I: vaginal ring (n =
      25) and group II: COC pills (n = 25). Menstrual blood loss (MBL) was assessed at
      baseline, 1, 3 and 6 months (while on treatment) and at 9 months (3 months after
      stopping therapy). There was significant reduction in baseline pictorial blood
      loss assessment chart (PBAC) score from 440 +/- 188 (Mean +/- SD) to 178 +/- 95,
      139 +/- 117, 112 +/- 84 and 120 +/- 108 in group I and from 452 +/- 206 to 204 +/
      152, 179 +/- 125, 176 +/- 164 and 202 +/- 167 in group II at 1, 3, 6 and 9
      months, respectively (p = 0.001). Reduction in MBL was 72% and 62% at 6 months
      and up to 71% and 55% at 9 months in group I and group II, respectively (p =
      0.001). Reduction in MBL with ring was greater at higher baseline PBAC score but
      lesser in patients with fibroid > 2 cm. Combined vaginal hormonal treatment for
      HMB is as effective as oral hormonal therapy, with minor and transient side
      effects and persistence of response after cessation of therapy. 

PMID- 26204127
TI  - Repression of arterial genes in hemogenic endothelium is sufficient for
      haematopoietic fate acquisition.
AB  - Changes in cell fate and identity are essential for endothelial-to-haematopoietic
      transition (EHT), an embryonic process that generates the first adult populations
      of haematopoietic stem cells (HSCs) from hemogenic endothelial cells. Dissecting
      EHT regulation is a critical step towards the production of in vitro derived
      HSCs. Yet, we do not know how distinct endothelial and haematopoietic fates are
      parsed during the transition. Here we show that genes required for arterial
      identity function later to repress haematopoietic fate. Tissue-specific,
      temporally controlled, genetic loss of arterial genes (Sox17 and Notch1) during
      EHT results in increased production of haematopoietic cells due to loss of Sox17
      mediated repression of haematopoietic transcription factors (Runx1 and Gata2).
      However, the increase in EHT can be abrogated by increased Notch signalling.
      These findings demonstrate that the endothelial haematopoietic fate switch is
      actively repressed in a population of endothelial cells, and that derepression of
      these programs augments haematopoietic output. 

PMID- 26204128
TI  - Condensin targets and reduces unwound DNA structures associated with
      transcription in mitotic chromosome condensation.
AB  - Chromosome condensation is a hallmark of mitosis in eukaryotes and is a
      prerequisite for faithful segregation of genetic material to daughter cells. Here
      we show that condensin, which is essential for assembling condensed chromosomes,
      helps to preclude the detrimental effects of gene transcription on mitotic
      condensation. ChIP-seq profiling reveals that the fission yeast condensin
      preferentially binds to active protein-coding genes in a transcription-dependent
      manner during mitosis. Pharmacological and genetic attenuation of transcription
      largely rescue bulk chromosome segregation defects observed in condensin mutants.
      We also demonstrate that condensin is associated with and reduces unwound DNA
      segments generated by transcription, providing a direct link between an in vitro
      activity of condensin and its in vivo function. The human condensin isoform
      condensin I also binds to unwound DNA regions at the transcription start sites of
      active genes, implying that our findings uncover a fundamental feature of
      condensin complexes. 

PMID- 26204132
TI  - Attitudes Towards Implementation of Store-and-Forward Telemental Health in
      Humanitarian Settings: Survey of Syrian Healthcare Providers.
AB  - BACKGROUND: Store-and-forward (S&F) telemedicine is thought to be most applicable
      in humanitarian settings. Unlike other kinds of telemental health (TMH), S&F
      requires engagement and active participation from healthcare providers in
      submitting text or audio-video clinical material for consultations. To implement
      such consultative systems there is a need to gauge providers' attitudes towards
      this technology. MATERIALS AND METHODS: An electronic survey was sent to Syrian
      healthcare providers (physicians and nonphysicians) who are affiliated with
      humanitarian nongovernmental organizations managing Syrians affected by war.
      After a description of what TMH and S&F are, participants were asked about their
      attitudes towards such services. RESULTS: Fifty-two providers responded to the
      electronic survey. Only results from providers inside Syria (n = 30) are
      presented. The majority of respondents had no experience with TMH. Half of the
      providers believed that mental healthcare can be provided through S&F and that
      there would be a benefit from such services. Respondents reported that cultural
      (68%), financial (84%), and technical (80%) barriers do exist for such services.
      When asked, providers believed that patients would agree to be audiotaped (58%)
      for the purpose of S&F compared with being videotaped (15%) (p = 0.007).
      CONCLUSIONS: Electronic surveys of healthcare workers in humanitarian settings
      are feasible. Providers in the Syrian humanitarian setting have little experience
      in TMH; however, they are open to using an S&F service while acknowledging
      cultural, financial, and technical barriers to the implementation.

PMID- 26204131
TI  - The Utility of the Swine Model to Assess Biological Rhythms and Their
      Characteristics during Different Stages of Residence in a Simulated Intensive
      Care Unit: A Pilot Study.
AB  - The purpose of this pilot study was to explore the utility of the mammalian swine
      model under simulated intensive care unit (sICU) conditions and mechanical
      ventilation (MV) for assessment of the trajectory of circadian rhythms of
      sedation requirement, core body temperature (CBT), pulmonary mechanics (PM) and
      gas exchange (GE). Data were collected prospectively with an observational time
      series design to describe and compare circadian rhythms of selected study
      variables in four swine mechanically ventilated for up to seven consecutive days.
      We derived the circadian (total variance explained by rhythms of tau between 20
      and 28 h)/ultradian (total variance explained by rhythms of tau between 1 and <20
      h) bandpower ratio to assess the robustness of circadian rhythms, and compare
      findings between the early (first 3 days) and late (subsequent days) sICU stay.
      All pigs exhibited statistically significant circadian rhythms (tau between 20
      and 28 h) in CBT, respiratory rate and peripheral oxygen saturation, but
      circadian rhythms were detected less frequently for sedation requirement,
      spontaneous minute volume, arterial oxygen tension, arterial carbon dioxide
      tension and arterial pH. Sedation did not appear to mask the circadian rhythms of
      CBT, PM and GE. Individual subject observations were more informative than group
      data, and provided preliminary evidence that (a) circadian rhythms of multiple
      variables are lost or desynchronized in mechanically ventilated subjects, (b)
      robustness of circadian rhythm varies with subject morbidity and (c) healthier
      pigs develop more robust circadian rhythm profiles over time in the sICU.
      Comparison of biological rhythm profiles among sICU subjects with similar
      severity of illness is needed to determine if the results of this pilot study are
      reproducible. Identification of consistent patterns may provide insight into
      subject morbidity and timing of such therapeutic interventions as weaning from
      MV.

PMID- 26204133
TI  - Regulation of Angiopoietin-Like Proteins (ANGPTLs) 3 and 8 by Insulin.
AB  - OBJECTIVE: Circulating ANGPTL8 has recently been used as a marker of insulin
      action. We studied expression and insulin regulation of ANGPTL8 and ANGPTL3 in
      vivo and in vitro. DESIGN AND METHODS: Expression of ANGPTL8 and ANGPTL3 was
      studied in 34 paired samples of human liver and adipose tissue. Effects of
      insulin on 1) plasma concentrations and adipose tissue expression of ANGPTL8 and
      ANGPTL3 (in vivo 6-h euglycemic hyperinsulinemia; n = 18), and 2) ANGPTL8 and
      ANGPTL3 gene and protein expression in immortalized human hepatocytes (IHH) and
      adipocytes were measured. Effect of ANGPTL3 on secretion of ANGPTL8 in cells
      stably overexpressing ANGPTL3, -8, or both was determined. RESULTS: ANGPTL3 was
      only expressed in the liver, whereas ANGPTL8 was expressed in both tissues. In
      vivo hyperinsulinemia significantly decreased both plasma ANGPTL8 and ANGPTL3 at
      3 and 6 hours. Insulin increased ANGPTL8 expression in human adipose tissue 14-
      and 18-fold at 3 and 6 hours and ANGPTL8 was the most insulin-responsive
      transcript on microarray. Insulin also increased ANPGTL8 in cultured adipocytes
      and IHH but the protein mainly remained intracellular. In vitro in IHH, insulin
      decreased ANGPTL3 gene expression and secretion of ANGPTL3 into growth medium.
      Overexpression of ANGPTL8 in CHO cells did not result in its release into culture
      medium while abundant secretion occurred in cells co-expressing ANGPTL3 and -8.
      CONCLUSIONS: Insulin decreases plasma ANGPTL3 by decreasing ANGPTL3 expression in
      the liver. Insulin markedly increases ANGPTL8 in adipose tissue and the liver but
      not in plasma. These data show that measurement of plasma ANGPTL3 but not -8
      reflects insulin action in target tissues.

PMID- 26204134
TI  - Sodium/Iodide Symporter Mutant V270E Causes Stunted Growth but No Cognitive
      Deficiency.
AB  - CONTEXT: Iodide (I(-)), an essential constituent of the thyroid hormones, is
      actively accumulated in the thyroid by the Na(+)/I(-) symporter (NIS), a key
      plasma membrane protein encoded by the slc5a5 gene. Mutations in slc5a5 cause I(
      ) transport defects (ITDs), autosomal-recessive disorders in which I(-)
      accumulation is totally or partially impaired, leading to congenital
      hypothyroidism. The characterization of NIS mutants has yielded significant
      insights into the molecular mechanism of NIS. OBJECTIVE: This study aimed to
      determine the basis of a patient's ITD clinical phenotype, by sequencing her
      slc5a5 gene. DESIGN: Genomic DNA was purified and the slc5a5 gene sequence
      determined. Functional in vitro studies were performed to characterize the V270E
      NIS mutant. PATIENT: The index patient was diagnosed with hypothyroidism with
      minimal radioiodide uptake in a normally located, although enlarged, thyroid
      gland. RESULTS: We identified a new NIS mutation: V270E. The patient had the
      compound heterozygous NIS mutation R124H/V270E. R124H NIS has been characterized
      previously. We show that V270E markedly reduces I(-) uptake via a pronounced (but
      not total) impairment of the protein's plasma membrane targeting. Remarkably,
      V270E is intrinsically active. Therefore, a negative charge at position 270
      interferes with NIS cell surface trafficking. The patient's minimal I(-) uptake
      enabled sufficient thyroid hormone biosynthesis to prevent cognitive impairment.
      CONCLUSIONS: A nonpolar residue at position 270, which all members of the SLC5A
      family have, is required for NIS plasma membrane targeting.

PMID- 26204137
TI  - Placental Angiogenic Factors Are Associated With Maternal Thyroid Function and
      Modify hCG-Mediated FT4 Stimulation.
AB  - CONTEXT: The thyroid has a high vascular density and this vascularity may be
      influenced by pregnancy-specific angiogenic factors. Proangiogenic placental
      growth factor (PlGF) and antiangiogenic soluble FMS-like tyrosine kinase-1
      (sFlt1; a vascular endothelial growth factor [VEGF] and PlGF antagonist) are
      important pregnancy-specific angiogenesis regulators. We previously showed that
      fetal levels of sFlt1 and PlGF are associated with newborn thyroid function.
      However, the maternal thyroid may also be affected as PlGF and VEGF are secreted
      into the maternal circulation and cause a concomitant increase of sFlt1 to
      overcome adverse effects of angiogenesis overstimulation. DESIGN, SETTING, AND
      PARTICIPANTS: Maternal sFlt1, PlGF, TSH, FT4, or human chorionic gonadotropin
      (hCG) levels were determined during early pregnancy (<18 wk) in 5517 women from
      the Generation R study. Analyses were adjusted for relevant covariates and
      interaction between hCG and angiogenic factors was investigated. RESULTS:
      Increasing levels of sFlt1 were associated with a decrease in FT4 and T4 (both P
      < .001), and an increased risk of subclinical hypothyroidism (odds ratio [OR] for
      high levels, 2.37; 95% CI, 1.16-4.83; P = .02) and isolated hypothyroxinemia
      (linear P = .02; OR, 3.05; 95% CI, 1.42-6.55; P = .004). Increasing levels of
      PlGF were associated with a decrease in TSH and FT4 levels (both P < .001), and
      an increased risk of isolated hypothyroxinemia (linear P = .002; OR, 1.77; 95%
      CI, 1.02-3.06; P = .04). High levels of hCG decreased the difference in FT4
      between low and high sFlt1. In women with high PlGF levels, the hCG-mediated
      increase in FT4 levels was attenuated. CONCLUSION: sFlt1 and PlGF are novel
      determinants of maternal thyroid (dys)function during early pregnancy and the
      response of the maternal thyroid function to hCG stimulation. These data provide
      novel insights into the pregnancy specific thyroid function physiology and
      suggest that high levels of pro- and anti-angiogenic factors may be a risk factor
      for adverse pregnancy outcomes via their effects on maternal thyroid function.

PMID- 26204136
TI  - Cholesterol Biosynthesis and Trafficking in Cortisol-Producing Lesions of the
      Adrenal Cortex.
AB  - CONTEXT: Cortisol-producing adenomas (CPAs), primary pigmented nodular
      adrenocortical disease (PPNAD), and primary macronodular adrenocortical
      hyperplasia (PMAH) cause ACTH-independent Cushing syndrome (CS). Investigation of
      their pathogenesis has demonstrated their integral link to the cAMP-dependent
      protein kinase signaling pathway. OBJECTIVE: The aim of this study was to
      identify differences in cholesterol biosynthesis among different CS-causing
      adrenocortical tumors. Because of the concomitant associations of cAMP levels
      with cholesterol and with steroid biosynthesis, we hypothesized that benign
      cortisol-producing tumors would display aberration of these pathways. DESIGN AND
      SETTING: Twenty-three patients with CPA, PPNAD, or PMAH who underwent
      adrenalectomy for CS were included in the study. Preoperative biochemical
      analyses were performed, and excised adrenal tissues were studied. MAIN OUTCOME
      MEASURES: Serum, urinary hormone levels, serum lipid profiles, and anthropometric
      data were obtained preoperatively. Adrenal tissues were analyzed for total
      protein, cholesterol, and neutral sterol content by mass spectrometry and
      expression of HMGCR, LDLR, ABCA1, DHCR24, and STAR genes. RESULTS: There were
      differences in cholesterol content and markers of cholesterol biosynthesis and
      metabolism that distinguished CPAs from PMAH and PPNAD; cholesterol, lathosterol,
      and lathosterol/cholesterol ratio were significantly higher in CPAs. ABCA1 mRNA
      was lower among CPAs compared to tissues from bilateral adrenocortical
      hyperplasia (PMAH and PPNAD), and mRNA expression of LDL-R, DCHR24, and HMGCR
      tended to be higher in CPA tumor tissues. CONCLUSION: CPAs displayed
      characteristics of "cholesterol-starved" tissues when compared to PPNAD and PMAH
      and appeared to have increased intrinsic cholesterol production and uptake from
      the periphery, as well as decreased cholesterol efflux. This has implications for
      a potential new way of treating these tumors.

PMID- 26204135
TI  - Adjustment of Open-Loop Settings to Improve Closed-Loop Results in Type 1
      Diabetes: A Multicenter Randomized Trial.
AB  - CONTEXT: Closed-loop control (CLC) relies on an individual's open-loop insulin
      pump settings to initialize the system. Optimizing open-loop settings before
      using CLC usually requires significant time and effort. OBJECTIVE: The objective
      was to investigate the effects of a one-time algorithmic adjustment of basal rate
      and insulin to carbohydrate ratio open-loop settings on the performance of CLC.
      DESIGN: This study reports a multicenter, outpatient, randomized, crossover
      clinical trial. PATIENTS: Thirty-seven adults with type 1 diabetes were enrolled
      at three clinical sites. INTERVENTIONS: Each subject's insulin pump settings were
      subject to a one-time algorithmic adjustment based on 1 week of open-loop (i.e.,
      home care) data collection. Subjects then underwent two 27-hour periods of CLC in
      random order with either unchanged (control) or algorithmic adjusted basal rate
      and carbohydrate ratio settings (adjusted) used to initialize the zone-model
      predictive control artificial pancreas controller. Subject's followed their usual
      meal-plan and had an unannounced exercise session. MAIN OUTCOMES AND MEASURES:
      Time in the glucose range was 80-140 mg/dL, compared between both arms. RESULTS:
      Thirty-two subjects completed the protocol. Median time in CLC was 25.3 hours.
      The median time in the 80-140 mg/dl range was similar in both groups (39.7%
      control, 44.2% adjusted). Subjects in both arms of CLC showed minimal time spent
      less than 70 mg/dl (median 1.34% and 1.37%, respectively). There were no
      significant differences more than 140 mg/dL. CONCLUSIONS: A one-time algorithmic
      adjustment of open-loop settings did not alter glucose control in a relatively
      short duration outpatient closed-loop study. The CLC system proved very robust
      and adaptable, with minimal (<2%) time spent in the hypoglycemic range in either
      arm.

PMID- 26204139
TI  - A Novel Mouse Model of Liver Ischemic/Reperfusion Injury and its Differences to
      the Existing Model.
AB  - BACKGROUND: Ischemia of the cephalad lobes (70% of liver mass) is a frequently
      employed mouse hepatic ischemia/reperfusion (I/R) model that does not involve
      outflow occlusion. This model produces results with relatively large variances.
      MATERIALS AND METHODS: A novel model of ischemia of the left lateral lobe (35% of
      liver mass) that involves temporarily occluding the blood supply to the cephalad
      lobes to expel blood followed by occlusion of both the inflow and outflow of the
      left lateral lobe, was developed. Mice in the 35% (novel) and 70% (existing)
      model groups were subjected to I/R injury, and biochemical and histological
      analyses of blood and liver samples were performed. Tissue oxygen partial
      pressure (tPO2) measurements in the ischemic lobes were also performed to
      determine whether the hepatic tissue was in a stable hypoxic state. Statistical
      analyses of the biochemical results, histological scores, and tPO2 levels were
      performed from which coefficients of variation (CV) were calculated. RESULTS: The
      CVs of the aminotransferase activities, histological scores, and tPO2 levels were
      much lower in the 35% group than those in the 70% group. The tPO2 measurements
      demonstrated that inflow occlusion in the 70% model did not result in a stable
      hypoxic state, even after the portal triads were ligated and severed, indicating
      that there was blood reflux from the vena cava, which would be responsible for
      the variations in results with the 70% I/R model. CONCLUSIONS: The new 35% I/R
      model leads to reproducible results because both inflow and outflow of the
      ischemic lobe are occluded.

PMID- 26204140
TI  - Bougie dilators: simple, safe and cost-effective treatment for Crohn's-related
      fibrotic anal strictures.
AB  - Anal strictures with fibrotic induration have been shown to develop in up to 50%
      of all patients with Crohn's disease (CD) with anal ulceration. We evaluate the
      technical feasibility, safety and long-term efficacy of bougie dilation for a
      subgroup of patients with symptomatic Crohn's-related fibrotic anal strictures.
      Bougie dilation is simple to perform, relatively inexpensive and has a low risk
      of complications.

PMID- 26204141
TI  - Assessing personal contributions in global surgery: By whose yardstick?
AB  - Over the past 2 decades, interest and involvement in global surgery as an
      evolving discipline have increased among practitioners and trainees. A demand for
      formal evaluation of global surgery projects has also increased with demands for
      outcomes and impact. However, there has been little or no encouragement or
      requirement for participants to formally assess their personal contribution
      either to a project or to the discipline itself owing to the volunteer-based
      nature of those involved. Though participant contribution cannot be easily
      measured, the experience can be used to foster professional development. We
      propose that this neglected opportunity be addressed and suggest a framework of
      intentional reflection and mentorship that can be applied as an integral part of
      the global surgery experience, from participants election through debriefing
      after the experience.

PMID- 26204142
TI  - Evaluating the reliability of surgical assessment methods in an orthopedic
      residency program.
AB  - BACKGROUND: Orthopedic surgical education in Canada has seen major change in the
      last 15 years. Work hour restrictions and external influence have led to new
      approaches for surgical training. With a change toward competency-based
      educational models under the CanMEDS headings there is a need to ensure the
      validity of modern assessment methods. Our objective was to evaluate the
      reliability of a currently used surgical skill assessment tool within an
      orthopedic residency program, as measured by the Surgical Encounters Form.
      METHODS: A surgical assessment tool has previously been created at our
      institution that comprises 15 items spanning 4 of the CanMEDS competencies.
      Results were blinded to the primary investigator and coded by a third party. The
      assessments were collected, and we measured percent agreement using Cronbach's
      alpha and Fleiss kappa. RESULTS: Over a 5-month period 11 staff members assessed
      10 residents. Eighty-eight assessments were completed in total. Weighted percent
      agreement was 90.9%. Cronbach's alpha averaged 0.865 for the medical expert role,
      0.920 for technical skills, 0.934 for the communicator role, 1.00 for the
      collaborator role and 1.00 for the health advocate role. The mean Fleiss kappa
      score was 0.147 (95% confidence interval -0.071 to 0.364), demonstrating low
      interrater reliability. CONCLUSION: Despite the development of a validated
      assessment tool to evaluate surgical skills acquisition, interrater reliability
      results suggest low levels of agreement among assessors.

PMID- 26204143
TI  - Perioperative factors predicting poor outcome in elderly patients following
      emergency general surgery: a multivariate regression analysis.
AB  - BACKGROUND: Older adults (>= 65 yr) are the fastest growing population and are
      presenting in increasing numbers for acute surgical care. Emergency surgery is
      frequently life threatening for older patients. Our objective was to identify
      predictors of mortality and poor outcome among elderly patients undergoing
      emergency general surgery. METHODS: We conducted a retrospective cohort study of
      patients aged 65-80 years undergoing emergency general surgery between 2009 and
      2010 at a tertiary care centre. Demographics, comorbidities, in-hospital
      complications, mortality and disposition characteristics of patients were
      collected. Logistic regression analysis was used to identify covariate-adjusted
      predictors of in-hospital mortality and discharge of patients home. RESULTS: Our
      analysis included 257 patients with a mean age of 72 years; 52% were men. In
      hospital mortality was 12%. Mortality was associated with patients who had higher
      American Society of Anesthesiologists (ASA) class (odds ratio [OR] 3.85, 95%
      confidence interval [CI] 1.43-10.33, p = 0.008) and in-hospital complications (OR
      1.93, 95% CI 1.32-2.83, p = 0.001). Nearly two-thirds of patients discharged home
      were younger (OR 0.92, 95% CI 0.85-0.99, p = 0.036), had lower ASA class (OR
      0.45, 95% CI 0.27-0.74, p = 0.002) and fewer in-hospital complications (OR 0.69,
      95% CI 0.53-0.90, p = 0.007). CONCLUSION: American Society of Anesthesiologists
      class and in-hospital complications are perioperative predictors of mortality and
      disposition in the older surgical population. Understanding the predictors of
      poor outcome and the importance of preventing in-hospital complications in older
      patients will have important clinical utility in terms of preoperative
      counselling, improving health care and discharging patients home.

PMID- 26204144
TI  - Diagnosis of VTE postdischarge for major abdominal and pelvic oncologic surgery:
      implications for a change in practice.
AB  - BACKGROUND: Extended thromboprophylaxis after hospital discharge following cancer
      surgery has been shown to reduce the incidence of venous thromboembolism (VTE);
      however, this practice has not been universally adopted. We conducted a
      population-based analysis to determine the proportion of patients with
      symptomatic VTE diagnosed within 90 days after initial discharge following major
      abdominopelvic cancer surgery who might have benefited from extended
      thromboprophylaxis. METHODS: We used the Manitoba Cancer Registry to identify
      patients who underwent major abdominopelvic cancer surgery between 2004 and 2009.
      The proportion in whom VTE was diagnosed during the initial hospital stay was
      determined by accessing the Hospital Separations Abstracts. The proportion in
      whom VTE was diagnosed after discharge was determined by examining repeat
      admissions within 90 days and by accessing Drug Programs Information Network
      records for newly prescribed anticoagulants. Detailed tumour and treatment
      specific data allowed calculation of VTE predictors. RESULTS: Of 6612 patients
      identified, 106 (1.60%) had VTE diagnosed during the initial stay and 96 (1.45%)
      presented with VTE after discharge. Among patients in whom VTE developed after
      discharge, 33.3% had a pulmonary embolus, 24% had deep vein thrombosis, and 6.3%
      had both. Predictors of presenting with VTE after discharge within 90 days of
      surgery included advanced disease, presence of other complications, increased
      hospital resource utilization, primary tumours of noncolorectal gastrointestinal
      origin and age younger than 45 years. The development of VTE was an independent
      predictor of decreased 5-year overall survival. CONCLUSION: The cumulative
      incidence of VTE within 90 days of major abdominopelvic oncologic surgery was
      3.01%, with about half (1.45%) having been diagnosed within 90 days after
      discharge.

PMID- 26204145
TI  - ?

PMID- 26204146
TI  - ?

PMID- 26204147
TI  - ?

PMID- 26204149
TI  - ?

PMID- 26204148
TI  - ?

PMID- 26204150
TI  - ?

PMID- 26204152
TI  - ?

PMID- 26204151
TI  - ?

PMID- 26204153
TI  - Cell signalling: One kinase targets many secreted proteins.

PMID- 26204161
TI  - Serum Sclerostin Levels in Newborns Born to Mothers With Vitamin D Deficiency.
AB  - AIM: Sclerostin inhibits osteoblast functions, differentiations, and survival
      rates. The aim of this study was to investigate the association between
      circulating sclerostin (an emerging biomarker and important regulator of bone
      formation) and neonatal parameters in mothers with vitamin D deficiency. METHOD:
      Forty-five mothers and their newborns were recruited in the study. The mothers
      were divided into 2 groups as vitamin D-deficient group 25(OH)D (25
      hydroxyvitamin D3 < 20 ng/mL) and vitamin D-sufficient group 25(OH)D (>20 ng/mL).
      Their newborns had measurements of weight, height, calcium, phosphate, alkaline
      phosphatase, sclerostin, and 25(OH)D at birth. RESULTS: The mothers with vitamin
      D deficiency had significantly lower vitamin D levels than the mothers with
      vitamin D sufficiency (8.7 [3.4] ng/mL vs 26.7 [4.0] ng/mL, P < 0.001). There
      were no significant differences between women with vitamin D deficiency and women
      with vitamin D sufficiency for sclerostin concentrations (205.4 [64.8] pg/mL vs
      291.6 [122.9] pg/mL). However, 25(OH)D (10.1 [8.1] ng/mL vs 33.4 [11.6] ng/mL, P
      < 0.001) and sclerostin concentrations (182.9 [15.3] pg/mL vs 288.8 [32.3] pg/mL,
      P = 0.01) were lower in newborns born by mothers with vitamin D deficiency
      compared and with newborns of mothers with vitamin D sufficiency. Circulating
      sclerostin measurements were not associated with 25(OH)D levels of both mothers
      and their newborns. CONCLUSIONS: We found significantly lower sclerostin levels
      in newborns born by women with vitamin D deficiency compared with newborns of
      nondeficient mothers.

PMID- 26204159
TI  - Short- and long-term effects of chromosome mis-segregation and aneuploidy.
AB  - Dividing cells that experience chromosome mis-segregation generate aneuploid
      daughter cells, which contain an incorrect number of chromosomes. Although
      aneuploidy interferes with the proliferation of untransformed cells, it is also,
      paradoxically, a hallmark of cancer, a disease defined by increased proliferative
      potential. These contradictory effects are also observed in mouse models of
      chromosome instability (CIN). CIN can inhibit and promote tumorigenesis. Recent
      work has provided insights into the cellular consequences of CIN and aneuploidy.
      Chromosome mis-segregation per se can alter the genome in many more ways than
      just causing the gain or loss of chromosomes. The short- and long-term effects of
      aneuploidy are caused by gene-specific effects and a stereotypic aneuploidy
      stress response. Importantly, these recent findings provide insights into the
      role of aneuploidy in tumorigenesis. 

PMID- 26204162
TI  - Diffusion Magnetic Resonance Imaging: What Water Tells Us about Biological
      Tissues.
AB  - Since its introduction in the mid-1980s, diffusion magnetic resonance imaging
      (MRI), which measures the random motion of water molecules in tissues, revealing
      their microarchitecture, has become a pillar of modern neuroimaging. Its main
      clinical domain has been the diagnosis of acute brain stroke and neurogical
      disorders, but it is also used in the body for the detection and management of
      cancer lesions. It can also produce stunning maps of white matter tracks in the
      brain, with the potential to aid in the understanding of some psychiatric
      disorders. However, in order to exploit fully the potential of this method, a
      deeper understanding of the mechanisms that govern the diffusion of water in
      tissues is needed. 

PMID- 26204166
TI  - Human adipose-derived stem cells enhance the survival and neuritogenesis of
      auditory neurons.
AB  - To evaluate the effect of human adipose-derived stem cells (ASCs) on auditory
      neurons with respect to a potential application in cochlear implantation. Spiral
      ganglions from rats were enzymatically dissociated and cocultured with or without
      ASCs in a coculture system. After 24 and 48 h, inserts with ASCs were removed and
      the dissociated neurons were fixed and stained. Then, a cell count of all
      dissociated cells and neurons was performed and the length of the neurites was
      evaluated. The potential effect of ASCs on the direction of neurite outgrowth was
      evaluated in a chemotaxis assay. For this, one chamber of the assay was filled
      with ASCs in medium and the other chamber filled with medium only. After 48 h,
      the growth direction of neurite outgrowth was evaluated. Cocultivation of
      auditory neurons with ASCs resulted in a marked and statistically significant
      increase in neurite outgrowth at 24 and 48 h after plating. Moreover, the number
      of surviving neurons and the percentage of neurons among the dissociated cells
      were higher in the coculture group compared with the control group during both
      observation periods. However, this difference was statistically significant only
      at one time point. A directional outgrowth of the neurons was not observed. ASCs
      appear to enhance the survival and the neuritogenesis of auditory neurons. This
      might be of particular interest for cochlear implantation, in which a proper
      function of the auditory nerve with a sufficient number of neurons and surviving
      peripheral processes is essential. 

PMID- 26204160
TI  - Sound of silence: the properties and functions of repressive Lys
      methyltransferases.
AB  - The methylation of histone Lys residues by Lys methyltransferases (KMTs)
      regulates chromatin organization and either activates or represses gene
      expression, depending on the residue that is targeted. KMTs are emerging as key
      components in several cellular processes, and their deregulation is often
      associated with pathogenesis. Here, we review the current knowledge on the main
      KMTs that are associated with gene silencing: namely, those responsible for
      methylating histone H3 Lys 9 (H3K9), H3K27 and H4K20. We discuss their
      biochemical properties and the various mechanisms by which they are targeted to
      the chromatin and regulate gene expression, as well as new data on the interplay
      between them and other chromatin modifiers. 

PMID- 26204167
TI  - Adnexal torsion in adolescents: update and review of the literature.
AB  - PURPOSE OF REVIEW: Adnexal torsion is a surgical emergency, which requires
      immediate recognition and prompt treatment. This article aims to systematically
      illustrate the most relevant approach to follow in cases of suspected adnexal
      torsion in adolescents. We based our evaluation of the role of clinical features,
      laboratory tests, and imaging on recent literature, till we consider the most
      appropriate surgical treatment. RECENT FINDINGS: The literature describes the
      conservative treatment for adnexal torsion, consisting of detorsion, as the best
      surgical approach to guarantee the future reproductive capacity of patients.
      Recent experimental studies have focused on the consequences of detorsion, which
      may cause ischemia-reperfusion damage and have speculated about the role of
      different drugs for its avoidance. SUMMARY: A systematic review of
      physiopathology, clinical picture, and imaging of adnexal torsion is certainly
      useful to identify as soon as possible this emergency condition. An early
      identification and an adequate treatment are indispensable in order to achieve a
      proper outcome for the patient. The choice of the appropriate surgical approach
      can be challenging and should be made on the basis of an accurate evaluation of
      the ovarian lesion. Therefore, it would be useful to perform an intraoperative
      frozen section analysis in selected cases.

PMID- 26204168
TI  - A Revolving Temporary Anchorage Cap Connecting to an Orthodontic Miniscrew Using
      In Vitro Experimental Testing: Safety and Biomechanical Evaluations.
AB  - PURPOSE: This study is to develop a plastic revolving (translation and rotation)
      temporary anchorage cap (TAC) as the orthodontic anchor and evaluate its
      biomechanical safety and clinical used feasibility. MATERIALS AND METHODS: The
      TAC was designed to connect onto a mini-implant head with 45-degree switching
      unit and extended arm for tying an orthodontic elastic chain/coil spring. The
      removal force between the TAC and mini-implant head and torque resistance on the
      mini-implant/bone interface were performed to evaluate the biomechanical safety.
      Clinical molar uprighting and mesial drive application were performed to reveal
      the TAC feasibility/capacity. RESULTS: The removal force was 43.95 N (>>finger
      pulling force 9.3 N) to prevent the TAC from detaching, and the torque resistance
      was 159.25 N.mm to maintain micromotion smaller than 30.4 MUm between the screw
      and bone. The strain value in using TAC treatment was found to be about 2 times
      that of traditional tracing (without using TAC) in molar uprighting/mesial drive
      application. CONCLUSIONS: The plastic revolving TAC can provide optional use with
      translation/rotation features to change the angles and directions in orthodontic
      tractions and increase treatment efficiency under biomechanical safety
      considerations.

PMID- 26204169
TI  - Additional Effects of Platelet-Rich Fibrin on Bone Regeneration in Sinus
      Augmentation With Deproteinized Bovine Bone Mineral: Preliminary Results.
AB  - PURPOSE: Platelet-rich fibrin (PRF) has been reported to contribute to bone
      regeneration; however, little is known about details with deproteinized bovine
      bone mineral (DBBM). This study aims to evaluate additional effects of PRF on
      bone regeneration in sinus augmentation with DBBM. MATERIALS AND METHODS: Sinus
      augmentations were made with DBBM/PRF mixture as lateral approach for 4 sinuses
      from 4 patients. Bone biopsies were obtained from posterior maxilla at the
      implant placements 7 or 10 months after sinus augmentations. Histological
      observations and histomorphometric analyses from augmented areas were performed.
      RESULTS: The new bone formation was found around the DBBMs with very good contact
      while surfaces of DBBMs were partly resorbed. Osteoclasts recognized the DBBMs
      for remodeling, followed by new bone running. The histomorphometric analyses
      revealed that mean percentages of newly formed bone were 31.7 +/- 1.2%, 21.0 +/-
      1.0%, 38.0 +/- 0.6%, and 47.0 +/- 0.6%, respectively (mean 34.5 +/- 5.7%).
      CONCLUSIONS: Additional effects of PRF could be found because of higher
      percentages of newly bone formation by DBBM/PRF mixture than those by DBBM
      individual in previous reports.

PMID- 26204170
TI  - Histomorphometric Evaluation of Ridge Preservation With and Without Connective
      Tissue Graft Over Buccal Plate Using Different Types of Bone Substitute: An
      Animal Study.
AB  - PURPOSE: The aim of this investigation was to assess the efficacy of using
      subepithelial connective tissue graft (CTG) over the buccal plate in conjunction
      with 2 different bone graft materials in fresh extraction sites. MATERIALS AND
      METHODS: Five mongrel dogs were used. Bilateral third (P3) mandibular premolars
      were extracted atraumatically. Animals were randomly divided in the 4
      experimental groups: no CT (NCT) + anorganic bovine bone (ABB), NCT + biphasic
      calcium phosphate (BCP), CT + ABB, and CT + BCP. This study evaluated tissue
      healing at 15, 30, 60, 90, and 120 days after socket preservation, using
      histologic and histomorphometric analyses. RESULTS: The main finding showed that
      all groups presented similar results with minor differences regardless of the use
      of CTG and type of bone substitute. A greater amount of residual graft particles
      was found when ABB was used. No differences in the histologic and
      histomorphometric analysis were found when comparing the use of CTG with NCTG for
      ridge preservation procedure. CONCLUSION: Within the limitations of this animal
      study, the use of CTG to overbuild the buccal plate at time of tooth extraction
      did not affect the quality of bone regeneration.

PMID- 26204172
TI  - Association study between reward dependence and a functional BDNF polymorphism in
      adult women offspring of alcohol-dependent probands.
AB  - Thirty-five healthy adult women offspring of alcohol-dependent probands (AWOA)
      were compared with 63 healthy controls to test whether personality dimensions on
      the Temperament and Character Inventory questionnaire were associated with the
      brain-derived neurotrophic factor Val66Met polymorphism in offspring. We found a
      significantly lower reward dependence score in AWOA compared with the controls.
      The brain-derived neurotrophic factor Val66Met polymorphism may be involved in
      this difference as the lower reward dependence score was found only in AWOA
      carrying the Val allele. 

PMID- 26204173
TI  - A new species of Entobdella Blainville in Lamarck, 1818 (Monogenea: Capsalidae:
      Entobdellinae) from the Greenland halibut, Reinhardtius hippoglossoides.
AB  - A previously undescribed species of Entobdella is reported from the skin of the
      Greenland halibut, Reinhardtius hippoglossoides (Pleuronectiformes,
      Pleuronectidae). Entobdella whittingtoni sp. nov. differs from other species of
      Entobdella, including skin parasites of the related pleuronectids Hippoglossus
      hippoglossus (Atlantic halibut) and H. stenolepis (Pacific halibut), in lacking
      papillae on the ventral surface of the haptor. Other characteristics of E.
      whittingtoni are as follows: the absence of vitelline follicles lateral to the
      pharynx thereby exposing gut caeca in this region of whole mounts; the presence
      of a circular feature of unknown function, resembling a rosette in sections,
      attached to the wall of the internal male accessory reservoir; the lack of eyes.
      Papillae are also absent from the ventral surface of the haptor of the gill
      parasitic entobdelline Branchobdella pugetensis, a gill parasite of the
      pleuronectid Atheresthes stomias. This raises the question as to whether this
      gill parasite has evolved from a skin-parasitic ancestor similar to E.
      whittingtoni. An answer to this question requires a more detailed study of the
      male reproductive apparatus of B. pugetensis and the use of molecular techniques
      to explore the relationship between B. pugetensis and E. whittingtoni. 

PMID- 26204174
TI  - Molecular epidemiology, risk factors and hematochemical alterations induced by
      Theileria annulata in bovines of Punjab (India).
AB  - Bovine tropical theileriosis, caused by Theileria annulata, is one of the
      economically important fatal tick borne haemoprotozoan diseases of dairy animals.
      The aim of present investigation was to map the distribution of T. annulata in
      bovines of Punjab state of India in relation to various risk factors including
      age, sex of animals, location and management of farms. In a cross sectional
      study, a total of 1278 blood samples were randomly collected from twenty
      districts falling in five major agro-climatic zones of Punjab. All the samples
      were screened by blood smear examination followed by polymerase chain reaction
      targeting SSU rRNA gene for Theileria spp. PCR positive samples (n = 386) for
      Theileria spp. were then analyzed for T. annulata by amplification of Tams1 gene.
      Overall prevalence of T. annulata was found to be 29.26% in Punjab, with highest
      in western Zone (40.49%, 95% CI = 35.57-45.41) and lowest in submountain zone
      (18.90%, 95% CI = 13.73-24.06). The propensity of incidence of T. annulata was
      found to be highest in cross bred cattle (32.40%, 95% CI = 29.87-34.94), followed
      by indigenous cattle (19.64%, 95% CI = 10.67-28.61) and buffaloes (19.2%, 95% CI
      = 14.99-23.41). Between the two sexes, incidence of T. annulata was higher in
      female animals. Calves less than 6 months of age were found to be more prone to
      theileriosis. 

PMID- 26204175
TI  - Molecular characterization of Setaria digitata from Mithun (Bos frontalis).
AB  - Mithun is a strongly built hill animal of Southeast Asia and plays an important
      role in the socio-economic and cultural life of the tribal population. Setaria
      digitata isolated from peritoneal cavity of mithun both from Arunachal Pradesh
      and Nagaland were characterized based on conserved region of 12SrDNA, 28SrDNA and
      ITS-2 and mitochondrial gene CoxI. Based on sequence analysis, it was found to be
      99% similarity with Srilankan isolate of S. digitata. 

PMID- 26204176
TI  - Redescription and genetic characterization of Philometra lagocephali Moravec et
      Justine 2008 (Nematoda: Philometridae) from Lagocephalus lunaris (Bloch and
      Schneider) (Tetraodontiformes: Tetradontidae) in the South China Sea.
AB  - Philometra lagocephali Moravec et Justine, 2008 was redescribed using light and
      scanning electron microscopy based on the new material collected from the
      lunartail puffer Lagocephalus lunaris (Bloch et Schneider) (Tetraodontiformes:
      Tetradontidae) in the South China Sea. Our specimens are identical with the
      original description in the body size of gravid female, the width of cephalic and
      caudal end, the number and arrangement of cephalic papillae, the relative length
      of the oesophagus to body length, the size of ventriculus, the morphology of
      oesophageal bulb and posterior end, and the body size of larvae. In addition,
      specimens of P. lagocephali were also characterized using molecular methods by
      sequencing and analysing the small ribosomal DNA (18S rDNA) and mitochondrial
      cytochrome c coxidase subunit 1 (cox1) target regions. Phylogenetic analyses of
      genus Philometra base on 18S rDNA sequences was made using Mega 5.2. The results
      confirmed P. lagocephali is a valid species. It's the first molecular study of
      this species. These new morphological and molecular data contributed to a more
      precise and rapid diagnosis of this hitherto poorly known philometrid nematode. 

PMID- 26204177
TI  - Ophthalmology hospital wards contamination to pathogenic free living Amoebae in
      Iran.
AB  - The present study was conducted to determine the occurrence of potentially
      pathogenic free-living amoeba in ophthalmology wards in reference hospitals in
      Iran. Since an increasing number of Acanthamoeba Keratitis cases after eye
      surgery and eye trauma have been recently observed in this country, it could be
      possible that the disinfection procedures undertaken in the clinical setting may
      not have a good hygiene and disinfection procedures, hence the aim of this study.
      Therefore, 42 dust and biofilm samples were collected from different areas of
      ophthalmology wards and checked for the presence of FLA using morphological
      criteria, PCR based analysis and DNA sequencing. Of the 42 samples from dust and
      biofilm sources, 18(42.86%) isolates were found to contain FLA and 12(92.3%)
      isolates belonged to Acanthamoeba T4 genotype. Isolation of the pathogenic
      genotype T4 from medical instruments, including slit lamp in corneal wards, may
      be a threat for patients undergoing eye surgery in these wards. Other FLA
      isolated in this study included Acanthamoeba genotype T5, Vahlkampfia sp,
      Naegleria australiensis, Vermamoeba vermiformis and Echinamoeba exudans. To our
      knowledge, this is the first report of the presence of potentially pathogenic FLA
      in ophthalmology wards in Iran. Improved disinfection methods and monitoring of
      hospitals ward are thus necessary in this area in order to minimize the risk of
      infection in patients. 

PMID- 26204178
TI  - Eye fluke infection status in Baltic cod, Gadus morhua, after three decades and
      their use as ecological indicators.
AB  - Eye flukes of the genus Diplostomum were recorded with a prevalence of 7.4% and a
      mean intensity of 11.9 (range 1-75) parasites per fish in eye lenses of a total
      of 188 Atlantic cod, Gadus morhua, sampled in the Southeastern Baltic Sea from
      March 2013 to February 2014. A slight decrease of infection level, among the fish
      with body length ranging from 30 to 89.5 cm, was found when data were compared to
      a corresponding survey in the 1980s. Due to imprecise species identification of
      eye flukes based on morphometric analyses we present, as a baseline for further
      studies, rDNA sequences from a subsample of 19 eye flukes based on sequencing of
      a part of 18S, ITS-1, 5.8S, ITS-2 and part of 28S. We discuss the use of eye
      fluke recordings in Baltic cod as an environmental indicator due to the
      dependence of the parasite's life cycle on biotic (occurrence of snail and bird
      hosts) and abiotic (temperature and salinity) parameters.

PMID- 26204179
TI  - Aplectana dubrajpuri sp. nov. (Nematoda: Cosmocercidae) in Hoplobatrachus
      tigerinus (Anura: Dicroglossidae) from Dubrajpur, Birbhum, West Bengal, India.
AB  - Aplectana dubrajpuri sp. nov., recovered from the rectum of Indian bull frog,
      Hoplobatrachus tigerinus, collected from Dubrajpur in the Birbhum district of
      West Bengal, India, is described and illustrated. This species is characterised
      by absence of gubernaculum and differs from other species of Aplectana which lack
      a gubernaculum (viz. A. akhrami, A. artigasi, A. chilensis, A. crossodactyli, A.
      crucifer, A. delirae, A. meridionalis, A. papillifera, A. praeputialis, A. tarija
      and A. vercammeni) by smaller size of males and females, absence of somatic
      papillae in females and number and distribution of caudal papillae in males which
      include 3 pairs precloacal, 1 pair adcloacal, 14 pairs postcloacal and a single
      unpaired small papilla on the upper lip of cloaca. Aplectana dubrajpuri sp. nov.
      represents 51st species assigned to the genus and 3rd from India. 

PMID- 26204180
TI  - Trypanosoma cruzi DTU TcII presents higher blood parasitism than DTU TcI in an
      experimental model of mixed infection.
AB  - Trypanosoma cruzi (Tc), the causative agent of Chagas disease, affects millions
      of people worldwide. One of the major characteristics of T. cruzi is related to
      its heterogeneity due to the variability of its biological properties, parasite
      growth rates, infectivity, tissue tropism, morbidity and virulence among
      different isolates observed during experimental or human infection. Moreover,
      presence of mixed infections in the same host in endemic areas is a matter of
      study due to its impact on clinical manifestations and disease progression. In
      this study, we evaluated the biological behavior of two Tc I strains AQ1-7 (AQ)
      and MUTUM (MT) and one Tc II strain (JG) during the acute phase of infection, in
      unique and mixed infections. A patent blood parasitism was detected only in mice
      inoculated with JG strain . In addition blood parasitism parameters (peak and
      average blood parasitism) were positively associated when JG and AQ strains were
      combined. In contrast, a negative association was observed in the JG+MUTUM group.
      The predominance of TcII strain over TcI strains was highlighted using the LSSP
      PCR technique, which was performed in samples from hemoculture. Thus, this study
      showed important biological differences between different T. cruzi strains and
      discrete typing units (DTUs) in acute phase. Finally, we observed that blood
      parasitism during early period of infection seems to be more related to DTU than
      to a specific strain. 

PMID- 26204181
TI  - Molecular phylogeny and ultrastructure of Myxobolus cf. cuneus, a parasite of
      patinga hybrid and Henneguya pseudoplatystoma, a parasite of pintado hybrid.
AB  - Through morphological, histopathological and ultrastructural analysis of
      Myxobolus cuneus Adriano, Arana et Cordeiro, 2006 and Henneguya pseudoplatystoma
      Naldoni, Arana, Maia, Ceccarelli, Tavares, Borges, Pozo et Adriano, 2009 were
      identified infecting pacu respectively (Piaractus mesopotamicus) and hybrid
      pintado (Pseudoplatystoma corruscans x Pseudoplatystoma reticulatum) taken from
      Brazilian fish farms. The present study describes 18S rDNA sequencing of
      Myxobolus cf. cuneus infecting the spleen of farmed patinga, a hybrid fish
      resulting from the crossing of P. mesopotamicus x Piaractus brachypomus, and H.
      pseudoplatystoma found in farmed hybrid pintado from the state of Sao Paulo,
      Brazil. The study also provides new details of the host-parasite interface of M.
      cf. cuneus, which reveal that the plasmodial wall is composed of a single
      membrane connected to the plasmodium ectoplasm by numerous pinocytic canals. The
      plasmodia also displayed asynchronous development but had disporic pansporoblasts
      at different developmental stages; immature and mature spores were found at
      different depth levels of the plasmodium. Maximum likelihood phylogenetic
      analysis showed that M. cf. cuneus appeared as a sister species of Henneguya
      pellucida Adriano, Arana et Cordeiro, 2005 in a sub-clade composed mainly of
      myxosporean parasites of characiforms, and that H. pseudoplatystoma clustered in
      a sub-clade composed of Henneguya/Myxobolus spp. parasites of siluriform fish. 

PMID- 26204182
TI  - Supplementary data of Henneguya leporinicola (Myxozoa, Myxosporea) a parasite of
      Leporinus macrocephalus from fish farms in the state of Sao Paulo, Brazil.
AB  - Henneguya leporinicola is a parasite of the gill filament of Leporinus
      macrocephalus, a characiform fish belonging to the Anostomidae family, which is
      of major economic importance. Despite the damage it causes in fish, little is
      known about this parasite. Therefore, a study was undertaken with fourteen
      specimens of L. macrocephalus taken from fish farms in the state of Sao Paulo.
      The fish were collected and examined searching for lesions and/or myxosporean
      plasmodia. One of the specimens (7.14%) contained white elongated plasmodia in
      the gill filament. The mature spores had elongated bodies with polar capsules of
      equal size and a caudal length greater than body length. Morphological
      characteristics identified the parasite as H. leporinicola. Molecular analysis of
      the 18S rDNA sequence resulted in a 1954 bp, demonstrating significant genetic
      differences with previously described species of Henneguya/Myxobolus.
      Phylogenetic analysis comparing the 18S rDNA sequence of H. leporinicola with
      other species, previously described in South America, and the 20 closest species
      as indicated by BLASTn Max Score showed H. leporinicola as a basal branch of a
      subclade composed by Henneguya spp. parasite of characiform hosts. 

PMID- 26204183
TI  - Prevalence and genotype of Giardia duodenalis in dairy cattle from Northern and
      Northeastern part of Thailand.
AB  - The aims of this study were to determine prevalence and genotype of Giardia
      duodenalis in feces of dairy cattle from the northern part and the northeastern
      part of Thailand. A total of 900 fecal samples were collected directly from
      rectum and examined by using zinc sulphate centrifugal flotation technique and
      polymerase chain reaction (PCR). The overall prevalence of G. duodenalis in dairy
      cows was 5.0 % (45/900) by zinc sulphate centrifugal flotation and 6.0 % (54/900)
      by PCR. Genotypes of G. duodenalis found in this study were Assemblage AI and E.
      The results indicated that dairy cattle may act as a potential risk of Giardia
      transmission among animals and humans (especially Assemblage AI). 

PMID- 26204184
TI  - Comparison of pathogens infection level in Ips typographus (Coleoptera:
      Curculionidae) beetles sampled in pheromone traps and at place of overwintering.
AB  - The importance of pathogens in the population dynamics of Ips typographus remains
      a subject of ongoing debate. The main objective of our experiment was to compare
      the pathogen infection levels of individuals overwintering in bark with the
      levels of individuals from the same population captured with pheromone traps and
      thereby to determine primary answers as to whether it can be confirmed that
      pathogenic organisms affect the flight ability of bark beetles or their ability
      to leave their places of overwintering. A total of 402 I. typographus individuals
      were analyzed at a study location under limited management. Three pathogens were
      confirmed to be present: the gregarine Gregarina typographi, the virus ItEPV, and
      the microsporidium Nosema typographi. Infection levels of Gregarina typographi
      and ItEPV were the same in beetles collected at places of overwintering and in
      those beetles collected in pheromone traps within the immediate vicinity. As
      these pathogens infect the host's intestine, the tendency to leave the places of
      overwintering is apparently not diminished. A similar analysis and comparison of
      pathogens located in the fat body might bring different results, as our study
      only detected N. typographi in a single dissected adult spruce bark beetle. 

PMID- 26204185
TI  - A new species of Isospora (Apicomplexa: Eimeriidae) from eastern coachwhip,
      Coluber flagellum flagellum (Reptilia: Ophidia) from Oklahoma.
AB  - Between June 2013 and August 2014, four eastern coachwhips, Coluber flagellum
      flagellum were collected from Arkansas (n = 2) and Oklahoma (n = 2) and their
      faeces examined for coccidian parasites. One (25%) harboured an isosporan that we
      describe here as new. Oocysts of Isospora kiamichiensis sp. n. were spheroidal to
      subspheroidal with a uni-layered wall and measured (length * width, L * W) 25.0 *
      22.2 MUm, with an L/W ratio of 1.1. A micropyle, oocyst residuum and polar
      granule were absent. Sporocysts were ovoidal, 13.9 * 9.4 MUm, with an L/W ratio
      of 1.5. A pronounced, button-like Stieda body was present as well as a substieda
      body. A sporocyst residuum was present as dispersed granules. This is the first
      isosporan and fourth coccidian reported from eastern coachwhip snakes. In
      addition, a single oocyst of an unknown choleoeimerian was recovered from this
      host. 

PMID- 26204186
TI  - The first report of Trichinella pseudospiralis presence in domestic swine and T.
      britovi in wild boar in Bosnia and Herzegovina.
AB  - The Balkans is endemic for nematodes of the genus Trichinella in both domestic
      and wild animals. The high prevalence of these zoonotic pathogens in animals
      linked with the food habits to consume raw meat and meat derived products
      resulted in a very high prevalence of trichinellosis in humans living in this
      European region. In spite of numerous epidemiological investigations carried out
      in this region, very few information is available on the Trichinella species
      circulating in Bosnia and Herzegovina. Trichinella spp. larvae were isolated from
      a domestic pig reared in a backyard and from a hunted wild boar whose meat had
      been the source of trichinellosis in one case. Both Trichinella pseudospiralis
      and T. spiralis have been identified in the domestic pig, whereas, T. britovi was
      detected in the wild boar. While, T. spiralis is the Trichinella species most
      frequently detected in domestic pigs, T. pseudospiralis has been previously
      documented in domestic pigs only three times in Russia, Slovakia and Croatia. The
      detection of T. britovi in the wild boar confirms that this nematode is the most
      frequent species circulating among wildlife of Europe. 

PMID- 26204187
TI  - Dirofilariasis - an emergent human parasitosis in Romania.
AB  - Changing vector habitats due to climate change increase the risk of less common
      vector-borne diseases spreading to temperate areas. An example of such a disease
      is dirofilariasis. The present article is a case presentation of ocular
      dirofilariasis. The peculiarities of this case and its implications to public
      health are presented herein, in addition to a literature review of the
      epidemiological data regarding dirofilariasis in dogs and humans. A16-year-old
      adolescent, who had never travelled outside Galati County, was admitted to the
      hospital's pediatric department with conjunctival edema, foreign body perception,
      redness and local pain in the left eye. A parasitological exam identified
      Dirofilaria repens. The outcome of the condition was favorable. Although canine
      dirofilariasis is more often encountered by veterinary practices, only few human
      cases had hither to been reported in Romania, none in Galati County. A national
      Romanian prevalence study on dirofilariasis in animals is called for in order to
      improve the management of the disease, both in veterinary and human medicine. 

PMID- 26204188
TI  - Two new picobiin mite species (Acari: Cheyletoidea: Syringophilidae) parasitizing
      passerine birds in Guyana.
AB  - Two new picobiin mite species (Cheyletoidea: Syringophilidae) are described from
      passeriform birds in Guyana, Rafapicobia automoli sp. nov. parasitizing two
      furnariid species Automolus ochrolaemus (Tschudi) (type host) and Automolus
      rufipileatus (Pelzeln) (Passeriformes: Furnariidae) and Neopicobia herbicolae sp.
      nov. from Emberizoides herbicola (Vieillot) (Thraupidae). Additionally, Picumnus
      exilis (Lichtenstein) (Piciformes: Picidae) is recorded as a new host species for
      Neopicobia hepburni Glowska et Laniecka, 2014. 

PMID- 26204189
TI  - New species of Prosotocus (Digenea; Pleurogenidae) and other helminths in
      Euphlyctis cyanophlyctis (Anura: Dicroglossidae) from Punjab, India.
AB  - Prosotocus punjabensis sp. nov. (Digenea, Pleurogenidae) from the intestine of
      the water skipper, Euphlyctis cyanophlyctis (Anura, Dicroglossidae), from Punjab,
      India is described and illustrated. Prosotocus punjabensis sp. nov. is the 13th
      Oriental species assigned to the genus and is separated from its congeners based
      upon the morphology of the vitellaria and cecal terminations. In addition, E.
      cyanophlyctis was found to harbour three species of Nematoda, Aplectana
      macintoshii, Cosmocerca kalesari and an unidentified species assigned to
      Cosmocerca. 

PMID- 26204191
TI  - Variations in cercarial production and the level of in vitro activation of
      metacercariae of two different isolates of Fasciola hepatica.
AB  - Fasciola hepatica infections cause large economic losses and are a serious
      veterinary medicine problem in many regions of the world. Recent studies
      examining fascioliasis in the bison population from Bialowieza National Park have
      shown that the prevalence of infection with this parasite is up to 100%. Liver
      flukes isolated from bison from Bialowieza National Park in Poland were compared
      with a fluke strain originally obtained from the Central Veterinary Laboratory,
      Weybridge, UK, to determine variations in cercarial production and establish the
      ability of their metacercariae to activate in vitro. Some small differences in
      cercarial production between the two isolates are shown, while significant
      differences in the ability of their metacercariae to activate in vitro were
      observed. 

PMID- 26204190
TI  - Chimeric DNA vaccines encoding Eimeria acervulina macrophage migration inhibitory
      factor (E.MIF) induce partial protection against experimental Eimeria infection.
AB  - Chimeric DNA vaccines co-expressing Eimeria acervulina macrophage migration
      inhibitory factor (E.MIF) and chicken IL-2 (IL-2) or interferon-gamma (IFN-gamma)
      were constructed and their efficacies against E. acervulina were evaluated. The
      open reading frame (ORF) of E.MIF was cloned from E. acervulina merozoites and
      subcloned into the eukaryotic expression vector pVAX1 with chicken cytokine gene
      IFN-gamma or IL-2 to construct the DNA vaccines pVAX-E.MIF-IFN-gamma, pVAX-E.MIF
      IL-2 and pVAX-E.MIF. The in vivo transfection of the target genes was detected by
      use of reverse transcription polymerase chain reaction (RT-PCR) and Western blot.
      Immunizations were carried out by vaccinating chickens twice with a dose rate of
      100 MUg intramuscularly. Seven days post second immunization, all chickens except
      the unchallenged control group were challenged orally with 1 * 105 sporulated
      oocysts of E. acervulina. Seven days later, the duodenum was collected. The
      results showed that the target genes were expressed effectively in vivo. DNA
      vaccines and the recombinant E.MIF protein could alleviate body weight loss and
      duodenal lesions significantly compared to the control groups. Furthermore, pVAX
      E.MIF-IL-2 and pVAX-E.MIF-IFN-gamma induced anticoccidial indexs (ACIs) of 179.12
      and 170, respectively, which were significantly higher than that of pVAX-E.MIF
      (ACI = 162.31). Our results demonstrated that E.MIF is a potential vaccine
      candidate against E. acervulina and chicken IFN-gamma or IL- 2 may be used as
      genetic adjuvants to improve the efficacies of DNA vaccines against avian
      coccidiosis. 

PMID- 26204192
TI  - Evaluation of reactivity to Echinococcus spp. among rural inhabitants in Poland.
AB  - A group of 172 rural inhabitants from eastern Poland (68 males and 104 females,
      mean age 49.0 +/- 12.0 years) was examined for the presence of antibodies against
      Echinococcus granulosus and Echinococcus multilocularis. A population of 38
      healthy urban dwellers from the city of Lublin (17 males and 21 females, mean age
      36.2 +/- 9.6 years) were examined as a control group. Sera of 22 rural
      inhabitants (12.8%) reacted positively to Echinococcus granulosus hydatid fluid
      antigen in the screening test. A cross-reactivity was observed with two serum
      samples that tested positive in ELISA for E. granulosus. Three serum samples were
      tested positive for E. multilocularis using the Em2plus ELISA assay and also
      positive for Western blot. None of the members of control group showed the
      presence of a seropositive reaction to Echinococcus spp. The reactivity to
      Echinococcus spp. among rural inhabitants decreased with age and this correlation
      was statistically significant (R = -0.197151, p = 0.009535). The percentage of
      positive findings was the highest (50.0%) in the youngest age group (14-20). No
      significant correlations were found between responses to interview questions
      (possession of domestic and farm animals, contact with wild animals, eating
      unwashed berries, drinking unboiled water) and the presence of seropositive
      reactions to Echinococcus spp. The presented results seem to indicate that
      echinococcosis is still a current problem in Poland that should not be neglected
      and, moreover, indicates the need for improvement in the routine laboratory
      diagnostics of Echinococcus spp. by standardizing the ELISA and Western blot
      tests. 

PMID- 26204193
TI  - Wild boars meat as a potential source of human trichinellosis in Poland: current
      data.
AB  - Trichinellosis is an epidemiological problem with a global distribution. In
      Poland a substantial increase of the wild boar population has been observed since
      2010, together with an increased incidence of trichinellosis after ingestion of
      raw or undercooked wild boar products containing Trichinella spp. larvae.
      However, the actual number of human cases remains particularly difficult to
      determine. The aim of the present study was to determine the current prevalence
      and spread of these parasites within wild boars. The diaphragm pillars and tongue
      from 833 wild boars were collected from 2010 to 2014, as well as one wild boar
      meat sausage known to be a source of infection. The samples were tested for
      Trichinella spp. using pepsin digestion. Recovered larvae were identified at
      species level by multiplex polymerase chain reaction (multiplex PCR). The overall
      prevalence in all examined samples was found to be 2.0% (17/833). Recovered
      larvae were identified as T. spiralis and T. britovi (9/18 and 5/18,
      respectively). T. spiralis larvae were isolated from the sausage. Mixed infection
      was confirmed only once. Three isolates were not identified. The results of our
      study confirm that the wild boar plays a key role in the maintenance of
      Trichinella nematodes through the sylvatic cycle. 

PMID- 26204194
TI  - Liver fluke (Fasciola hepatica) naturally infecting introduced European brown
      hare (Lepus europaeus) in northern Patagonia: phenotype, prevalence and potential
      risk.
AB  - Fascioliasis has recently been included in the WHO list of Neglected Zoonotic
      Diseases. Besides being a major veterinary health problem, fascioliasis has large
      underdeveloping effects on the human communities affected. Though scarcely
      considered in fascioliasis epidemiology, it is well recognized that both native
      and introduced wildlife species may play a significant role as reservoirs of the
      disease. The objectives are to study the morphological characteristics of
      Fasciola hepatica adults and eggs in a population of Lepus europaeus, to assess
      liver fluke prevalence, and to analyze the potential reservoir role of the
      European brown hare in northern Patagonia, Argentina, where fascioliasis is
      endemic. Measures of F. hepatica found in L. europaeus from northern Patagonia
      demonstrate that the liver fluke is able to fully develop in wild hares and to
      shed normal eggs through their faeces. Egg shedding to the environment is close
      to the lower limit obtained for pigs, a domestic animal whose epidemiological
      importance in endemic areas has already been highlighted. The former, combined
      with the high prevalence found (14.28%), suggest an even more important role in
      the transmission cycle than previously considered. The results obtained do not
      only remark the extraordinary plasticity and adaptability of this trematode
      species to different host species, but also highlight the role of the European
      brown hare, and other NIS, as reservoirs capable for parasite spillback to
      domestic and native cycle, representing a potentially important, but hitherto
      neglected, cause of disease emergence. 

PMID- 26204195
TI  - Molecular characterization of Fascioloides magna (Trematoda: Fasciolidae) from
      south-western Poland based on mitochondrial markers.
AB  - The giant liver fluke, Fascioloides magna, is a veterinary important liver
      parasite of free living and domestic ruminants. This originally North American
      parasite was introduced along with its cervid hosts to Europe where it has
      established three permanent natural foci - in northern Italy, central and
      southern parts of the Czech Republic and the Danube floodplain forests. The first
      record on fascioloidosis in Poland originated from the Lower Silesian Forest in
      south-western Poland and since then an occurrence of F. magna in this country has
      not been documented. Recently, the parasitological examination of red deer
      (Cervus elaphus elaphus) from the Lower Silesian Wilderness (south-western
      Poland) revealed the presence of F. magna eggs. In order to determine the genetic
      interrelationships of the Polish giant liver fluke individuals, they were
      molecularly analyzed by mitochondrial cytochrome c oxidase subunit I (cox1) and
      nicotinamide dehydrogenase subunit I (nad1) and compared with haplotypes of so
      far studied European populations of the parasite. The study revealed the genetic
      uniformity of F. magna specimens from Poland with part of individuals from the
      Czech natural focus. Note: Nucleotide sequence data reported in this paper are
      available in the GenBank, EMBL and DDBJ databases under the accession numbers
      KP635008-9.

PMID- 26204196
TI  - First Molecular Characterization of Aspiculuris tetraptera (Nematoda:
      Heteroxynematidae) from Mus musculus (Rodentia: Muridae) in India.
AB  - Mus musculus (Rodentia: Muridae) were infected by a nematode belonging to the
      order Oxyurida. According to external morphological characters it was found to be
      Aspiculuris tetraptera Schulz, 1924. Present communication deals with molecular
      characterization of A. tetraptera infecting intestine of Mus musculus in Meerut
      (U.P.), India. A partial sequence of 18S ribosomal and cytochrome c oxidase
      subunit 1 (Cox 1) mitochondrial DNA analyses were performed. Sequence
      corresponding to 18S rRNA and mt Cox 1 gene was identical to sequences reported
      for A. tetraptera on GenBank. These results confirm the taxonomic validation of
      A. tetraptera parasitizing Mus musculus. This is the first report of molecular
      study of A. tetraptera in India. 

PMID- 26204197
TI  - Diagnosis and therapy of Capillaria plica infection: report and literature
      review.
AB  - Worldwide, data on Capillaria (Pearsonema) plica infections of the urinary tract
      in domestic carnivores are limited. Nevertheless, cystitis with hematuria,
      dysuria or pollakiuria may suggest a C. plica infection. A three-year old dog
      from Poland showing pollakiuria and hematuria was presented. At urine analysis,
      C. plica eggs were found in the urine sediment. The dog was unsuccessfully
      treated with a daily oral dose of fenbendazole 50 mg/kg BW for 5 days, while a
      single subcutaneous administration of ivermectin 0.2 mg/kg BW once effectively
      eliminated C. plica infection. 

PMID- 26204198
TI  - Roles of the NFkappaB and glutathione pathways in mature human erythrocytes.
AB  - Anucleated erythrocytes were long considered as oxygen-transporting cells with
      limited regulatory functions. Components of different nuclear signaling pathways
      have not been investigated in those cells, yet. Surprisingly, we repeatedly found
      significant amounts of transcription factors in purified erythrocyte
      preparations, i.e. nuclear factor kappaB (NFkappaB), and major components of the
      canonical NFkappaB signaling pathway. To investigate the functional role of
      NFkappaB signaling, the effects of the preclinical compounds Bay 11-7082 and
      parthenolide on the survival of highly purified erythrocytes were investigated.
      Interestingly, both inhibitors of the NFkappaB pathway triggered erythrocyte
      programmed cell death as demonstrated by enhanced phospholipid scrambling
      (phosphatidylserine exposure) and cell shrinkage. Anucleated erythrocytes are an
      ideal cellular model allowing the study of nongenomic mechanisms contributing to
      suicidal cell death. As NFkappaB inhibitors might also interfere with the anti
      oxidative defense systems of the cell, we measured the levels of reduced
      glutathione (GSH) after challenge with the inhibitors. Indeed, incubation of
      erythrocytes with Bay 11-7082 clearly decreased erythrocyte GSH levels. In
      conclusion, the pharmacological inhibitors of the NFkappaB pathway Bay 11-7082
      and parthenolide interfere with the survival of erythrocytes involving mechanisms
      other than disruption of NFkappaB-dependent gene expression. Besides affecting
      erythrocyte survival, NFkappaB inhibition and induction of erythrocyte
      phosphatidylserine exposure may influence blood clotting. Future studies will be
      aimed at discriminating between NFkappaB-dependent and NFkappaB-independent GSH
      mediated effects of Bay 11-7082 and parthenolide on erythrocyte death.

PMID- 26204199
TI  - Electrochemical immunosensor for detection of epidermal growth factor reaching
      lower detection limit: toward oxidized glutathione as a more efficient blocking
      reagent for the antibody functionalized silver nanoparticles and antigen
      interaction.
AB  - Blocking reagent is of vital importance for an immunosensor because it ensures
      the antifouling of the sensing interface and thus selective determination of the
      target. This Letter investigates a small inactive peptide, oxidized glutathione
      (GSSG), to replace the commonly used bovine serum albumin (BSA) as blocking
      reagent for immunosensor fabrication to lower the detection limit of
      electrochemical immunosensors. The EGF (epidermal growth factor) detection as an
      example is used here to compare the blocking effects from GSSG and BSA,
      respectively. The relatively big size of BSA sterically hinders EGF and antibody
      functionalized silver nanoparticles (Ab-AgNPs) binding. By comparison, GSSG
      cannot hinder EGF and Ab-AgNPs binding since it is much smaller than EGF,
      verified by scanning electron microscopy (SEM) results. The established GSSG
      blocking-based immunosensor for EGF reaches a very low detection limit of 0.01
      pM, exhibits wide linearity range between 0.1 pM and 0.1 MUM and is more
      sensitive than the BSA blocking strategy. The proposed GSSG-blocking strategy in
      the immunoassay paves an attractive platform for other biomolecules to reach a
      lower detection limit. 

PMID- 26204201
TI  - Revisiting the Cause of Focal Neurological Deficits and Profound Dyspnea at High
      Altitude-The Potential Role of Patent Foramen Ovale.
AB  - A 49-year-old man developed weakness due to acute infarction of the left
      precentral gyrus. Subsequent investigation revealed a large patent foramen ovale
      (PFO), and it was concluded that the cerebral infarction was likely caused by a
      paradoxical embolus in association with the PFO. In hindsight, the PFO may
      explain several previous transient focal neurological deficits, some of which had
      occurred at high altitude and had been attributed to migraine. Furthermore, the
      large PFO may explain several episodes of profound shortness of breath that had
      occurred while exercising at high altitude during his lifetime, typically above
      5000 m. Arterial hypoxemia due to hypobaric hypoxia may be exacerbated in
      individuals with PFO and affect physical performance at high altitude.

PMID- 26204202
TI  - Clinical and Dosimetric Variables Related to Outcome After Treatment of Graves'
      Disease With 550 and 1110 MBq of 131I: Results of a Prospective Randomized Trial.
AB  - : Therapy of Graves' hyperthyroidism (HTG) with I is still mostly performed on an
      empirical basis. The present study was carried out to evaluate clinical and
      dosimetric variables associated with outcome in HTG therapy, which could
      contribute to planning and defining the most appropriate activity to be
      administered. METHODS: Patients with HTG were randomly assigned to therapy with
      555 MBq (15mci) or 1110 MBq (30 mCi) of I. Estimation of thyroid radiation
      absorbed dose was made according to MIRD methodology. Success was defined as
      clinical/laboratory euthyroidism or hypothyroidism one year after therapy. The
      association between clinical, laboratory, and dosimetric variables with 1-year
      outcome was measured using bivariate analysis, followed by logistic regression.
      RESULTS: Ninety-one patients included completed the follow-up. Therapeutic
      success was observed in 77 (84.6%) of them, in a greater proportion when 1110 MBq
      of I was administered as compared with 550 MBq (94.8% vs 77.4%, P = 0.02).
      Besides administered activity, multivariate analysis indicated that outcome was
      related to patient age and gland mass. A higher therapeutic success rate was
      achieved with doses greater than 300 Gy as compared with doses less than 300 Gy
      (89% vs 60%, P = 0.01). CONCLUSION: Administered activity, age, and gland mass
      were related to the outcome. Radiation absorbed dose, although not significant
      according to multivariate analysis, may be used as a quantitative parameter in
      therapy planning, with a target dose of 300 Gy. In cases where a rapid and
      efficient response to radioiodine treatment is required, adoption of a simplified
      protocol employing high activities is justified.

PMID- 26204200
TI  - Bacterial Vaginosis and Subclinical Markers of Genital Tract Inflammation and
      Mucosal Immunity.
AB  - Bacterial vaginosis (BV) has been linked to an increased risk of human
      immunodeficiency virus (HIV) acquisition and transmission in observational
      studies, but the underlying biological mechanisms are unknown. We measured
      biomarkers of subclinical vaginal inflammation, endogenous antimicrobial
      activity, and vaginal flora in women with BV and repeated sampling 1 week and 1
      month after completion of metronidazole therapy. We also compared this cohort of
      women with BV to a healthy control cohort without BV. A longitudinal, open label
      study of 33 women with a Nugent score of 4 or higher was conducted. All women had
      genital swabs, cervicovaginal lavage (CVL) fluid, and cervicovaginal biopsies
      obtained at enrollment and received 7 days of metronidazole treatment. Repeat
      sampling was performed approximately 1 week and 1 month after completion of
      therapy. Participant's baseline samples were compared to a healthy, racially
      matched control group (n=13) without BV. The CVL from women with resolved BV
      (Nugent 0-3) had significantly higher anti-HIV activity, secretory leukocyte
      protease inhibitor (SLPI), and growth-related oncogene alpha (GRO-alpha) levels
      and their ectocervical tissues had significantly more CD8 cells in the
      epithelium. Women with persistent BV after treatment had significantly higher
      levels of interleukin-1beta, tumor necrosis factor alpha (TNF-alpha), and
      intercellular adhesion molecule 1 (ICAM-1) in the CVL. At study entry,
      participants had significantly greater numbers of CCR5(+) immune cells and a
      higher CD4/CD8 ratio in ectocervical tissues prior to metronidazole treatment,
      compared to a racially matched cohort of women with a Nugent score of 0-3. These
      data indicate that BV is associated with changes in select soluble immune
      mediators, an increase in HIV target cells, and a reduction in endogenous
      antimicrobial activity, which may contribute to the increased risk of HIV
      acquisition. 

PMID- 26204203
TI  - Imaging Nigrostriatal Dopaminergic Deficit in Holmes Tremor with 18F-PR04.MZ
      PET/CT.
AB  - Holmes tremor is an infrequent clinical syndrome characterized by unilateral
      rest, postural, and action tremor often secondary to a brain lesion. We herein
      report an interesting case of Holmes tremor studied with PET and F-PR04.MZ, a new
      high-affinity radioligand for dopamine transporters, currently under
      investigation at our center. F-PR04.MZ-PET can be useful to study the integrity
      of the nigrostriatal dopaminergic system to improve diagnosis and therapeutic
      outcome in patients with Holmes tremor and Parkinson disease. 

PMID- 26204204
TI  - Quality and Safety in Health Care, Part III: To Err is Human.
AB  - A groundbreaking report on safety in health care was the Institute of Medicine
      publication, To Err is Human. It indicated that there were up to 98,000 deaths
      per year because of medical errors. This report resulted in major discussions in
      the media, Congress, and medical circles and had multiple effects on health care.
      Much greater attention was subsequently spent on patient safety by members of the
      health-care team, including administrators and researchers. However, a decade and
      a half later, much still needs to be done. 

PMID- 26204205
TI  - 99mTc-MDM Brain SPECT for the Detection of Recurrent/Remnant Glioma-Comparison
      With ceMRI and 18F-FLT PET Imaging: Initial Results.
AB  - PURPOSE: To evaluate the diagnostic use of an indigenously developed single vial
      ready to label (with Tc) kit preparation of bis-methionine-DTPA (Tc-MDM) for the
      detection of recurrent/residual glioma. MATERIALS AND METHODS: We prospectively
      studied 32 patients (21 male and 11 female subjects aged 43.0+/-16.0 years) with
      clinical suspicion of postoperative recurrent/residual glioma. After radical
      radiotherapy (54.0-60.0 Gy) with or without concurrent temozolomide as indicated,
      Tc-MDM SPECT and ceMRI of the brain was performed in all the patients and F-FLT
      PET imaging in 16 of 32 patients. RESULTS: MDM SPECT and ceMRI findings were
      concordant in 28 patients (15 positive and 13 negative). The findings were
      discordant in the remaining 5 patients, with positive ceMRI and negative MDM
      SPECT in 2 patients and negative ceMRI and positive MDM-SPECT in 3 patients. Tc
      MDM-SPECT, F-FLT PET, and ceMRI scan findings were positive in 9 of 16 and
      negative in 5 of 16 patients. In the remaining 2 of 16 patients, both F-FLT-PET
      and Tc-MDM-SPECT were positive, but ceMRI was negative. Sensitivity, specificity,
      PPV, NPV, and DA of Tc-MDM-SPECT for diagnosing recurrent/residual glioma were
      88.24%, 81.25%, 83.3%, 86.7%, and 84.8%, respectively. CONCLUSIONS: The
      diagnostic accuracy of Tc-bis-methionine (MDM)-SPECT imaging was comparable with
      that of ceMRI and F-FLT-PET and may be useful in the management of glioma
      patients in the postsurgical follow-up period. This imaging technique may be of
      special interest in peripheral hospitals/developing countries lacking access to
      expensive PET/cyclotron technology. However, comparison with the existing "gold
      standard" PET tracers, especially with C-11-methionine-PET imaging and
      histopathological correlation, is warranted in a large cohort of glioma patients
      through multicentric studies.

PMID- 26204206
TI  - Glucagonoma Pancreatic Neuroendocrine Tumor Treated With 177Lu DOTATATE Induction
      and Maintenance Peptide Receptor Radionuclide Therapy.
AB  - A 56-year-old man presented with a history of 2 prior resections of a recurrent
      pancreatic glucagonoma in the past 4 years. Workup revealed new liver and
      abdominal nodal metastases with a rising serum glucagon level. He was started on
      peptide receptor radionuclide therapy with Lu DOTATATE, and his disease
      stabilized, while his glucagon levels decreased and also stabilized. After 4
      induction and 2 maintenance cycles, he remains progression free for 23 months. 

PMID- 26204207
TI  - Bilateral Crossed "Unfused" Renal Ectopia.
AB  - Ectopic kidney-uncrossed or crossed, or with and without fusion-is a common
      congenital developmental anomaly. Commonly employed imaging modalities used for
      evaluating such condition include ultrasonography, IV pyelography, and contrast
      enhanced CT scan. Here in, we describe a rare case report of an incidentally
      detected bilateral crossed renal ectopia without fusion on Tc-DTPA scan in the
      setting of inconclusive ultrasonography and deranged renal function. 

PMID- 26204208
TI  - IgG4-Related Tubulointerstitial Nephritis Pattern in 18F-FDG PET/CT.
AB  - A 17-year-old adolescent girl was admitted with chronic arthralgia, Raynaud
      phenomenon, pericarditis, and evidences of chronic diffuse inflammation. F-FDG
      PET/CT scan was performed to search systemic vasculitis and showed diffuse
      moderate uptake in the kidneys. We suggested the existence of a nephritis, but
      the ultrasonography result was normal, and no treatment was introduced. Another F
      FDG PET/CT scan was performed 7 months later to explore abdominal pain. It showed
      again diffuse intense uptake in both kidneys. A proteinuria was highlighted, and
      renal biopsy allowed to diagnose IgG4-related disease. 

PMID- 26204209
TI  - Bone Marrow Involvement in Unknown Acute Myeloid Leukemia Detected by 18F-FDG
      PET/MRI.
AB  - A 83-year-old patient with inflammatory syndrome, unknown fever, and intense
      lumbar pain underwent diagnostic imaging for suspicion of spondylodiscitis. Fused
      F-FDG PET/MRI images showed heterogeneous hypermetabolism in the lumbar spine
      characterized by infiltrative lesions and adjacent necrotic tissue. Peripheral
      blood analysis revealed leukoerythroblastic changes, whereas bone marrow biopsy
      was highly hypercellular and revealed an acute myeloid leukemia with 70%
      infiltration of blasts of erythroid lineage. The intensive lumbar pain and
      elevated lactate dehydrogenase level are suggestive of bone marrow necrosis as
      seen in the PET/MRI. Our case emphasizes the usefulness of fused PET/MRI imaging
      for metabolic characterization of AML. 

PMID- 26204210
TI  - FDG PET/CT Findings of Recurrent Respiratory Papillomatosis With Malignant
      Degeneration in the Lung.
AB  - Recurrent respiratory papillomatosis is a rare benign disease caused by HPV-6 or
      HPV-11. The tumors may rarely undergo malignant degeneration. We performed FDG
      PET/CT in a patient experiencing recurrent respiratory papillomatosis who had
      pulmonary involvement. Although squamous cell carcinoma was detected in one of
      the pulmonary masses, squamous metaplasia with dysplasia were detected in the
      other one. Intensity modulated radiation therapy was performed to treat the
      malignancy. Second FDG PET/CT was performed 15 months after radiotherapy. 

PMID- 26204211
TI  - PET/CT and Bremsstrahlung Imaging After 90Y DOTANOC Therapy for Rectal Net With
      Liver Metastases.
AB  - Peptide receptor radionuclide therapy with Lu or Y is promising with successful
      results in somatostatin receptor-positive tumors. In all radiation therapies,
      knowledge of the radiation dose received by the target, and other organs in the
      body is essential to evaluate the risks and benefits of any procedure. We report
      a case of liver metastases from a rectal neuroendocrine tumor, which was treated
      with Y DOTANOC. Posttreatment whole-body planar images were acquired through
      Bremsstrahlung radiations of Y on a gamma-camera, and thoracolumbar PET/CT images
      were acquired on PET. 

PMID- 26204212
TI  - Correlation of SUV-Derived Indices With Tumoral Aggressiveness of Gliomas in
      Static 18F-FDOPA PET: Use in Clinical Practice.
AB  - PURPOSE: Glioma grading is necessary for prognostic evaluation and optimal
      treatment decisions. The aims of this study were to establish whether a
      correlation between F-FDOPA uptake with tumor grade was observed and to determine
      which of the SUV-derived indices was the best correlated. PATIENTS AND METHODS:
      Thirty-one patients were retrospectively included (mean [SD] age, 36.8 [12.1]
      years) including 21 proven low-grade tumors due to histology, imaging, and
      clinical follow-up and 10 histologically proven high-grade tumors. Static PET
      acquisitions were postreconstructed between the 10th and 30th minute after
      injection of F-FDOPA. Regions of interest of 20 mm were applied to tumors, and
      isocontoured volumes were defined at levels of 50% and 80% of the peak intensity
      voxel. Background was quantified with 30-mm-diameter regions of interest on
      contralateral striatum and centrum semioval. Tumoral uptake was evaluated with
      the following SUV-derived indices: SUVmax, SUVmean, SUVmax, and SUVmean of
      isocontoured volume, tumor/striatum ratio (T/S), and tumor/normal brain ratio
      (T/N). RESULTS: All the SUV-derived indices tested were significantly correlated
      with tumor grade, considering low-grade and high-grade groups (P < 0.05), except
      for the SUVmean 50%. The 2 best-correlated indices were SUVmean T/N and SUVmean
      T/S, with correlation coefficients of 0.561 and 0.522, respectively. Receiver
      operating characteristic analysis defined optimal thresholds of 1.33 and 1 for
      sensitivity and specificity of 71% and 100% and 67% and 100%, respectively.
      CONCLUSIONS: F-FDOPA PET SUV-derived indices are routinely available information
      that enables accurate discrimination of low-grade and high-grade gliomas. The
      best-correlated indices were SUVmean T/N and SUVmean T/S with thresholds of 1.33
      and 1.

PMID- 26204213
TI  - A General Cutoff Level Combined With Personalized Dynamic Change of Serum
      Carcinoembryonic Antigen Can Suggest Timely Use of FDG PET for Early Detection of
      Recurrent Colorectal Cancer.
AB  - PURPOSE: FDG PET that has been used is good for diagnosing asymptomatic
      colorectal cancer (CRC) recurrence in patients with elevated serum
      carcinoembryonic antigen (CEA) level. However, there is no reference level of CEA
      rise that would universally suggest the necessity of a PET study. The purpose of
      this retrospective study was to identify the high-risk group of CRC recurrence
      through an examination of the dynamics of the CEA level rise as a recurrence
      indicator. PATIENTS AND METHODS: Between July 2002 and May 2010, 112 patients (59
      men, 53 women; age, 18-87 years) had FDG PET for suspicious CRC recurrence
      indicated by elevated CEA level. We reviewed the PET results and the medical
      records for recurrence verification and calculated the ratio of increase and the
      velocity of change in CEA levels for risk stratification. RESULTS: The patient
      based sensitivity, specificity, and accuracy of PET are 96.6%, 91.3%, and 95.5%,
      respectively. The probability of recurrence positively correlated with the CEA
      level rise and the newly diagnosed disease stage. Carcinoembryonic antigen level
      greater than 13 ng/mL indicated significantly higher risks of recurrence. In
      patients with CEA level rise of 13 ng/mL or less, an increase over 3.34 times the
      individualized baseline also indicated high risks of recurrence. CONCLUSIONS: A
      posttreatment CEA level rise to greater than 13 ng/mL is suggestive of the
      optimal use of FDG PET, and so is a mild increase below 13 ng/mL at an increase
      rate over 3.34.

PMID- 26204214
TI  - 18F-FDG and 18F-NaF PET/CT Findings of a Multiple Myeloma Patient With Thyroid
      Cartilage Involvement.
AB  - Thyroid cartilage is a very rare extramedullary involvement location in multiple
      myeloma. We present both F-NaF and F-FDG PET/CT findings of a multiple myeloma
      patient with thyroid cartilage involvement. In this patient, increased FDG and
      more intensely increased NaF uptake were seen on thyroid cartilage. In addition,
      some bone lesions had more intense NaF than FDG uptake, and some were only NaF
      avid. Although F-FDG PET/CT has an important role in plasma cell neoplasms, we
      considered that F-NaF PET/CT is also very useful to detect small lytic lesions
      that might be overlooked on F-FDG PET/CT. 

PMID- 26204215
TI  - 99mTc-TRODAT-1 SPECT as a Potential Neuroimaging Biomarker in Patients With
      Restless Legs Syndrome.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a neurological sensory motor disorder
      of which pathophysiology remains sketchy. The present study was aimed to
      determine the diagnostic accuracy and potential of SPECT-TRODAT imaging in
      discriminating patients with RLS from normal individuals. PATIENTS AND METHODS: A
      total of 34 subjects, 22 diagnosed with RLS and 12 classified as normal, were
      enrolled. Brain SPECT images were acquired 180 minutes after IV injection of 740
      to 925 MBq (20-25 mCi) 99mTc-TRODAT-1 using a double-headed gamma-camera equipped
      with high-resolution fan-beam collimators. Regions of interest were drawn over
      the whole striatum, caudate, and putamen nucleus of each hemisphere on composite
      images of the 9 slices with the highest basal ganglia activity. The brain SPECT
      99mTc-TRODAT-1 imaging was compared with early-stage RLS patients and healthy
      volunteers groups. RESULT: SPECT imaging in RLS patients showed reduced
      radioactivity accumulation in the striatum profile. The major abnormal result
      observed is the significantly reduced uptake in striatal dopamine transporter
      density and activity. The symmetric striatal uptake was observed, and striatum
      dopamine transporter destiny was more impaired in patients with RLS disease.
      SPECT images also showed significant differences between patients and volunteers.
      CONCLUSIONS: This study supports that symptoms of restless legs resulted from the
      striatum of the brain dopaminergic system dysfunction.

PMID- 26204216
TI  - Primary Neuroendocrine Tumor in a Horseshoe Kidney With Positive 111In
      Pentetreotide Somatostatin Receptor Scintigraphy and Negative 18F-DOPA PET/CT.
AB  - Primary renal neuroendocrine tumors (NETs) are low-grade tumors with
      neuroendocrine differentiation and have been reported to arise most commonly in
      renal abnormalities such as horseshoe kidney. We report a case of a 54-year-old
      woman with history of invasive ductal breast carcinoma presenting several liver
      lesions. Histological findings finally revealed liver locations of a well
      differentiated NET. Imaging workup combining somatostatin receptor scintigraphy
      and F-DOPA PET/CT finally enable proper diagnosis of primary renal NET located on
      the isthmus of a horseshoe kidney. 

PMID- 26204217
TI  - Diaphragm and Laryngeal FDG Uptake With Hiccups.
AB  - F-FDG PET/CT study is a well-established investigation in diagnosis, treatment
      evaluation, and follow-up of malignant tumors. It is very important to know the
      normal biodistribution and physiologic uptake of F-FDG to prevent it from
      confusing as malignant disease. This article describes unusual but physiological
      uptake in the laryngeal and diaphragmatic muscles in a patient presenting as
      metastatic adenocarcinoma with unknown primary having hiccups. 

PMID- 26204218
TI  - Recurrent Urinary Bladder Paraganglioma Detected on 68Ga DOTANOC PET/CT.
AB  - Urinary bladder paraganglioma constitute only a small fraction of urinary bladder
      tumors. These rare tumors are well known for recurrences even after many years of
      surgery. Functional imaging with different radiotracers has been found to be
      useful to evaluate the extent, metastasis, and recurrence of paragangliomas. We
      report a case where Ga DOTANOC PET/CT successfully detected recurrence of a
      paraganglioma in the urinary bladder along with pelvic lymph nodal metastasis. 

PMID- 26204219
TI  - Glass Microspheres 90Y Selective Internal Radiation Therapy and Chemotherapy as
      First-Line Treatment of Intrahepatic Cholangiocarcinoma.
AB  - PURPOSE OF THE REPORT: Intrahepatic cholangiocarcinoma's incidence is increasing.
      We studied the efficacy of Y selective internal radiation therapy (SIRT) as first
      line treatment, with chemotherapy, and compared with the results of chemotherapy
      alone. PATIENTS AND METHODS: We retrospectively studied data from patients
      treated at our institution with glass microspheres SIRT for intrahepatic
      cholangiocarcinoma as part of first-line treatment in combination with
      chemotherapy. We compared results with those of similar patients treated in the
      ABC-02 study (a study in advanced biliary tract cancer that defined the current
      standard chemotherapy), assessed as not progressing after the first evaluation.
      We assessed progression-free survival (PFS) and overall survival (OS). RESULTS:
      Twenty-four patients were treated with SIRT. Chemotherapy was given concomitantly
      in 10 (42%), as induction before SIRT in 13 (54%) or after SIRT in 1 (4%). Grade
      3 adverse events were reported in 1 (4%). Median PFS after SIRT was 10.3 months.
      Longer PFS was observed when chemotherapy was given concomitantly than when
      chemotherapy was given before SIRT, with respective median of 20.0 versus 8.8
      months (P = 0.001). Median OS after SIRT was not reached. Eleven patients went to
      surgery (46%). Thirty-three patients in ABC-02 had locally advanced
      nonextrahepatic cholangiocarcinoma, not progressing after first evaluation. From
      the start of any treatment, the median PFS was 16.0 months in our cohort versus
      11.3 months in ABC-02 (P = 0.25), whereas the median OS was significantly higher
      in our cohort, not reached versus 17.9 months, respectively (P = 0.026).
      CONCLUSIONS: Selective internal radiation therapy combined with concomitant
      chemotherapy seems a promising strategy as first-line treatment for unresectable
      intrahepatic cholangiocarcinoma.

PMID- 26204220
TI  - Different Radioiodine Dose for Remnant Thyroid Ablation in Patients With
      Differentiated Thyroid Cancer: A Meta-analysis.
AB  - OBJECTIVE: Remnant thyroid ablation is crucial in the management of patients with
      differentiated thyroid cancer. However, the optimal dose of radioactive I for
      ablation is still controversial. This study aimed to compare the success rate of
      different activities of I for postoperative remnant ablation in randomized
      controlled trials (RCTs) and to determine the optimal dose. PATIENTS AND METHODS:
      Sources were retrieved from the Cochrane Library, Medline, Embase, Scopus, and
      Google Scholar until March 2014. All RCTs that assessed the efficacy of different
      doses of I for ablation were selected. After data extraction, statistics were
      performed by Review Manager 5.2 software. RESULTS: Seventeen RCTs were considered
      eligible, involving 3737 patients. The overall methodological quality of the
      studies was good. The rate of successful remnant ablation of low versus moderate
      I activities (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.80-1.00; P =
      0.06) and moderate versus high I activities (RR, 0.94; 95% CI, 0.89-1.00; P =
      0.05) showed no significant differences. However, high I activities had 11%
      higher successful ablation rate than low activities with an RR of 0.89 (95% CI,
      0.81-0.97; P = 0.008), which was significant. CONCLUSIONS: We summarized all
      available randomized evidence to demonstrate that high dose of I was
      significantly better than low dose to achieve successful remnant thyroid
      ablation.

PMID- 26204221
TI  - Unusual Visualization of the Ilium in Lower-Extremity Radionuclide Venography
      With 99mTc MAA.
AB  - A 60-year-old man was admitted with dilated cardiomyopathy, right-sided heart
      failure, and massive ascites. Tc-labeled macroaggregated albumin radionuclide
      venography of the lower extremities was performed, which showed stagnated
      radioactivity in the heart chambers, decreased uptake in the lung, and increased
      uptake in the proximal main renal veins and hepatic vein. Unexpectedly,
      radioactive accumulation in the ilium was noted on subsequent images acquired 3
      minutes later. 

PMID- 26204222
TI  - Volumetric parameters changes of sequential 18F-FDG PET/CT for early prediction
      of recurrence and death in patients with locally advanced rectal cancer treated
      with preoperative chemoradiotherapy.
AB  - : The goal of the present study was to determine whether volumetric parameters
      such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured
      by sequential F-FDG PET/CT imaging could be used as prognostic factors in
      patients with locally advanced rectal cancer (LARC) who received preoperative
      concurrent chemoradiotherapy. METHODS: A total 64 patients with LARC patients
      were included in the current study. All patients were evaluated by F-FDG PET/CT
      before and after 45 Gy of radiotherapy with concurrent oral capecitabine
      chemotherapy. Initial, second, and the percent changes ([INCREMENT], %) of
      semiquantitative and volumetric parameters were used to calculate recurrence-free
      survival (RFS) and overall survival (OS). The cutoff values of semiquantitative
      and volumetric parameters were determined by receiver operating characteristic
      curve analysis. The prognostic significance was assessed using univariate and
      multivariate Cox proportional hazard regression analysis. RESULTS: For RFS,
      American Joint Committee on Cancer (AJCC) stage (chi = 10.7, P = 0.002), surgical
      margin (+) (chi = 3.39, P = 0.037), lymphatic invasion (+) (chi = 6.8, P =
      0.0078), RECIST (Response Evaluation Criteria in Solid Tumors) (chi = 46.3, P <
      0.0001), SUVmax1 (chi = 10.1, P = 0.025), DeltaSUVmax (chi = 20.4, P < 0.0001),
      DeltaSUVmean (chi = 28.8, P < 0.0001), MTV1 (chi = 24.1, P < 0.0001), DeltaMTV
      (chi = 27.4, P < 0.0001), TLG1 (chi = 21.9, P < 0.0001), TLG2 (chi = 23.3, P <
      0.0001), and DeltaTLG (chi = 55.6, P < 0.0001) are associated prognostic factors.
      For OS, AJCC stage (chi = 6.0, P = 0.021), surgical margin (+) (chi = 3.2, P =
      0.042), lymphatic invasion (+) (chi = 3.8, P = 0.048), RECIST (chi = 10.4, P =
      0.0015), DeltaSUVmax (chi = 6.0, P = 0.013), DeltaSUVmean (chi = 10.5, P =
      0.0009), MTV1 (chi = 14.5, P = 0.0008), DeltaMTV (chi = 14.7, P = 0.0002), TLG1
      (chi = 15.8, P = 0.0002), TLG2 (chi = 13.5, P = 0.0006), and DeltaTLG (chi =
      17.5, P < 0.0001) are potent predictors. Multivariate Cox proportional hazard
      regression analyses revealed that the initial MTV (MTV1) and DeltaTLG were the
      potent predictors for RFS and OS. CONCLUSIONS: Our data suggest that MTV on
      initial pretreatment F-FDG PET/CT and DeltaTLG of sequential F-FDG PET/CT after
      preoperative concurrent chemoradiotherapy in LARC patients could provide
      prognostic information.

PMID- 26204223
TI  - Therapeutic effect of anti CEACAM6 monoclonal antibody against lung
      adenocarcinoma by enhancing anoikis sensitivity.
AB  - Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays a
      crucial role in tumorigenesis of lung cancer. However, the therapeutic potential
      for anti CEACAM6 monoclonal antibody (mAb) has only been limitedly explored.
      Here, we evaluate the therapeutic potential of naked anti CEACAM6 mAb against
      lung adenocarcinoma. Clone 8F5, recognizing B domain of CEACAM6, is established
      by immunizing A549 cells and screening for clones double positive for A549 and
      CEACAM6-Fc recombinant protein. We found that 85.7% of 70 resected lung
      adenocarcinoma tissue sections were positive for CEACAM6, whereas all squamous
      cell carcinoma examined were negative. A549 cells with high levels of CEACAM6
      demonstrated more aggressive growth nature and showed increased paclitaxel
      chemosensitivity upon 8F5 binding. Treatment with 8F5 to A549 decreased cellular
      CEACAM6 expression and reversed anoikis resistance. 8F5 also decreased cellular
      status of Akt phosphorylation and increased apoptosis via caspase activation. In
      a mouse model of lung adenocarcinoma with xenotransplanted A549 cells, 8F5
      treatment alone demonstrated 40% tumor growth inhibition. When combined with
      paclitaxel treatment, 8F5 markedly enhanced tumor growth inhibition, up to 80%.
      In summary, we demonstrate that anti CEACAM6 mAb is an effective therapeutic
      treatment for lung adenocarcinoma whose effect is further enhanced by combined
      treatment with paclitaxel. 

PMID- 26204224
TI  - Oligonucleotide aptamer-drug conjugates for targeted therapy of acute myeloid
      leukemia.
AB  - Oligonucleotide aptamers can specifically bind biomarkers on cancer cells and can
      be readily chemically modified with different functional molecules for
      personalized medicine. To target acute myeloid leukemia (AML) cells, we developed
      a single-strand DNA aptamer specific for the biomarker CD117, which is highly
      expressed on AML cells. Sequence alignment revealed that the aptamer contained a
      G-rich core region with a well-conserved functional G-quadruplex structure.
      Functional assays demonstrated that this synthetic aptamer was able to
      specifically precipitate CD117 proteins from cell lysates, selectively bound
      cultured and patient primary AML cells with high affinity (Kd < 5 nM), and was
      specifically internalized into CD117-expressing cells. For targeted AML
      treatment, aptamer-drug conjugates were fabricated by chemical synthesis of
      aptamer (Apt) with methotrexate (MTX), a central drug used in AML chemotherapy
      regimens. The formed Apt-MTX conjugates specifically inhibited AML cell growth,
      triggered cell apoptosis, and induced cell cycle arrest in G1 phase. Importantly,
      Apt-MTX had little effect on CD117-negative cells under the same treatment
      conditions. Moreover, exposure of patient marrow specimens to Apt-MTX resulted in
      selective growth inhibition of primary AML cells and had no toxicity to off
      target background normal marrow cells within the same specimens. These findings
      indicate the potential clinical value of Apt-MTX for targeted AML therapy with
      minimal to no side effects in patients, and also open an avenue to chemical
      synthesis of new, targeted biotherapeutics. 

PMID- 26204226
TI  - Formation of brominated disinfection by-products and bromate in cobalt catalyzed
      peroxymonosulfate oxidation of phenol.
AB  - Formation of halogenated disinfection by-products (DBPs) in sulfate radical
      [Formula: see text] based oxidation processes attracted considerable attention
      recently. However, the underlying reaction pathways have not been well explored.
      This study focused on the transformation of Br(-) in cobalt activated
      peroxymonosulfate (Co(2+)/PMS) oxidation process. Phenol was added as a model
      compound to mimic the reactivity of natural organic matter (NOM). It was revealed
      that Br(-) was efficiently transformed to reactive bromine species (RBS)
      including free bromine and bromine radicals (Br, [Formula: see text] , etc.) in
      Co(2+)/PMS system. [Formula: see text] played a principal role during this
      process. RBS thus generated resulted in the bromination of phenol and formation
      brominated DBPs (Br-DBPs) including bromoform and bromoacetic acids, during which
      brominated phenols were detected as the intermediates. Br-DBPs were further
      degraded by excessive [Formula: see text] and transformed to bromate ultimately.
      Free bromine was also formed in the absence of Co(2+), suggesting Br(-) could be
      oxidized by PMS per se. Free bromine was incorporated to phenol sequentially
      leading to Br-DBPs as well. However, Br-DBPs could not be further transformed in
      the absence of [Formula: see text] . This is the first study that elucidated the
      comprehensive transformation map of Br(-) in PMS oxidation systems, which should
      be taken into consideration when PMS was applied to eliminate contamination in
      real practice. 

PMID- 26204227
TI  - Long-term study on the impact of temperature on enhanced biological phosphorus
      and nitrogen removal in membrane bioreactor.
AB  - The study involved experimental observation and performance evaluation of a
      membrane bioreactor system treating municipal wastewater for nutrient removal for
      a period 500 days, emphasizing the impact of high temperature on enhanced
      biological phosphorus removal (EBPR). The MBR system was operated at relatively
      high temperatures (24-41  degrees C). During the operational period, the total
      phosphorus (TP) removal gradually increased from 50% up to 95% while the
      temperature descended from 41 to 24  degrees C. At high temperatures, anaerobic
      volatile fatty acid (VFA) uptake occurred with low phosphorus release implying
      the competition of glycogen accumulating organisms (GAOs) with polyphosphate
      accumulating organisms (PAOs). Low dissolved oxygen conditions associated with
      high wastewater temperatures did not appreciable affected nitrification but
      enhanced nitrogen removal. Dissolved oxygen levels around 1.0 mgO2/L in membrane
      tank provided additional denitrification capacity of 6-7 mgN/L by activating
      simultaneous nitrification and denitrification. As a result, nearly complete
      removal of nitrogen could be achieved in the MBR system, generating a permeate
      with no appreciable nitrogen content. The gross membrane flux was 43 LMH
      corresponding to the specific permeability (K) of 413 LMH/bar at 39  degrees C in
      the MBR tank. The specific permeability increased by the factor of 43% at 39 
      degrees C compared to that of 25  degrees C during long-term operation. 

PMID- 26204228
TI  - Asparagine Repeat Peptides: Aggregation Kinetics and Comparison with Glutamine
      Repeats.
AB  - Amino acid repeat runs are common occurrences in eukaryotic proteins, with
      glutamine (Q) and asparagine (N) as particularly frequent repeats. Abnormal
      expansion of Q-repeat domains causes at least nine neurodegenerative disorders,
      most likely because expansion leads to protein misfolding, aggregation, and
      toxicity. The linkage between Q-repeats and disease has motivated several
      investigations into the mechanism of aggregation and the role of Q-repeat length
      in aggregation. Curiously, glutamine repeats are common in vertebrates, whereas N
      repeats are virtually absent in vertebrates, but common in invertebrates. One
      hypothesis for the lack of N-repeats in vertebrates is biophysical; that is,
      there is strong selective pressure in higher organisms against aggregation-prone
      proteins. If true, then asparagine and glutamine repeats must differ
      substantially in their aggregation properties despite their chemical
      similarities. In this work, aggregation of peptides with asparagine repeats of
      variable length (12-24) were characterized and compared to that of similar
      peptides with glutamine repeats. As with glutamine, aggregation of N-repeat
      peptides was strongly length-dependent. Replacement of glutamine with asparagine
      caused a subtle shift in the conformation of the monomer, which strongly affected
      the rate of aggregation. Specifically, N-repeat peptides adopted beta-turn
      structural elements, leading to faster self-assembly into globular oligomers and
      much more rapid conversion into fibrillar aggregates, compared to Q-repeat
      peptides. These biophysical differences may account for the differing biological
      roles of N- versus Q-repeat domains.

PMID- 26204225
TI  - Combinatorial polymer matrices enhance in vitro maturation of human induced
      pluripotent stem cell-derived cardiomyocytes.
AB  - Cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) hold
      great promise for modeling human heart diseases. However, iPSC-CMs studied to
      date resemble immature embryonic myocytes and therefore do not adequately
      recapitulate native adult cardiomyocyte phenotypes. Since extracellular matrix
      plays an essential role in heart development and maturation in vivo, we sought to
      develop a synthetic culture matrix that could enhance functional maturation of
      iPSC-CMs in vitro. In this study, we employed a library of combinatorial polymers
      comprising of three functional subunits - poly-epsilon-caprolacton (PCL),
      polyethylene glycol (PEG), and carboxylated PCL (cPCL) - as synthetic substrates
      for culturing human iPSC-CMs. Of these, iPSC-CMs cultured on 4%PEG-96%PCL (each %
      indicates the corresponding molar ratio) exhibit the greatest contractility and
      mitochondrial function. These functional enhancements are associated with
      increased expression of cardiac myosin light chain-2v, cardiac troponin I and
      integrin alpha-7. Importantly, iPSC-CMs cultured on 4%PEG-96%PCL demonstrate
      troponin I (TnI) isoform switch from the fetal slow skeletal TnI (ssTnI) to the
      postnatal cardiac TnI (cTnI), the first report of such transition in vitro.
      Finally, culturing iPSC-CMs on 4%PEG-96%PCL also significantly increased
      expression of genes encoding intermediate filaments known to transduce integrin
      mediated mechanical signals to the myofilaments. In summary, our study
      demonstrates that synthetic culture matrices engineered from combinatorial
      polymers can be utilized to promote in vitro maturation of human iPSC-CMs through
      the engagement of critical matrix-integrin interactions. 

PMID- 26204229
TI  - Mouse Cd59b but not Cd59a is upregulated to protect cells from complement attack
      in response to inflammatory stimulation.
AB  - Universally expressed CD59 is the sole membrane complement regulatory protein
      that protects host cells from complement damage by restricting membrane attack
      complex assembly. The human gene encodes a single CD59, whereas the mouse gene
      encodes a duplicated CD59, comprising mCd59a and mCd59b, with distinct tissue
      distribution. Recently, we revealed that Sp1 regulates constitutive CD59
      transcription and that canonical nuclear factor kappa light chain enhancer of
      activated B cells (NF-kappaB) and cyclic AMP-responsive element-binding protein
      (CREB) regulate inducible CD59 transcription. However, the mechanisms that
      underlie mCd59 regulation remain unclear. Here we demonstrate that Sp1 controls
      broadly distributed mCd59a expression, whereas serum response factor (SRF) and
      canonical NF-kappaB regulate selectively expressed mCd59b. Tumor necrosis factor
      alpha in vitro and lipopolysaccharide in vivo remarkably enhance the expression
      of mCd59b but not mCd59a by activating SRF and NF-kappaB, thus protecting cells
      from complement attack. In addition, cAMP analog treatment also dramatically
      increases mCd59b but not mCd59a expression in a manner independent of CREB, SRF
      and NF-kappaB. Therefore, mCd59b but not mCd59a may be the responder to external
      inflammatory stimuli and may have an important role in complement-mediated mouse
      models of disease. 

PMID- 26204230
TI  - CTLA-4 as a genetic determinant in autoimmune Addison's disease.
AB  - In common with several other autoimmune diseases, autoimmune Addison's disease
      (AAD) is thought to be caused by a combination of deleterious susceptibility
      polymorphisms in several genes, together with undefined environmental factors and
      stochastic events. To date, the strongest genomic association with AAD has been
      with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic
      variants has been inconsistent. We have studied the association of 16 single
      nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a
      cohort comprising 691 AAD patients of Norwegian and UK origin with matched
      controls. We have also performed a meta-analysis including 1002 patients from
      European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD
      in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66),
      P=0.004), but not in UK patients. The same allele is associated with AAD in the
      total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker
      haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be
      associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51),
      P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for
      the development of AAD, and refines its mapping within the wider genomic locus. 

PMID- 26204231
TI  - Modification of mature non-reducible collagen cross-link concentrations in bovine
      m. gluteus medius and semitendinosus with steer age at slaughter, breed cross and
      growth promotants.
AB  - Increased meat toughness with animal age has been attributed to mature trivalent
      collagen cross-link formation. Intramuscular trivalent collagen cross-link
      content may be decreased by reducing animal age at slaughter and/or inducing
      muscle re-modeling with growth promotants. This hypothesis was tested in m.
      gluteus medius (GM) and m. semitendinosus (ST) from 112 beef steers finished at
      either 12 to 13 (rapid growth) or 18 to 20 (slow growth) months of age. Hereford
      Aberdeen Angus (HAA) or Charolais-Red Angus (CRA) steers were randomly assigned
      to receive implants (IMP), ractopamine (RAC), both IMP and RAC, or none
      (control). RAC decreased pyridinoline (mol/mol collagen) and IMP increased
      Ehrlich chromogen (EC) (mol/mol collagen) in the GM. In the ST, RAC increased EC
      (mol/mol collagen) but decreased EC (nmol/g raw muscle) in slow growing CRA
      steers. Also, IMP increased ST pyridinoline (nmol/g raw muscle) of slow-growing
      HAA steers. Results indicated alteration of perimysium collagen cross-links
      content in muscle in response to growth promotants. 

PMID- 26204232
TI  - Online feedback enhances early consolidation of motor sequence learning and
      reverses recall deficit from transcranial stimulation of motor cortex.
AB  - Feedback and monetary reward can enhance motor skill learning, suggesting reward
      system involvement. Continuous theta burst (cTBS) transcranial magnetic
      stimulation (TMS) of the primary motor area (M1) disrupts processing, reduces
      excitability and impairs motor learning. To see whether feedback and reward can
      overcome the learning impairment associated with M1 cTBS, we delivered real or
      sham stimulation to two groups of participants before they performed a motor
      sequence learning task with and without feedback. Participants were trained on
      two intermixed sequences, one occurring 85% of the time (the "probable" sequence)
      and the other 15% of the time (the "improbable" sequence). We measured sequence
      learning as the difference in reaction time (RT) and error rate between probable
      and improbable trials (RT and error difference scores). Participants were also
      tested for sequence recall with the same indices of learning 60 min after cTBS.
      Real stimulation impaired initial sequence learning and sequence knowledge recall
      as measured by error difference scores and impaired sequence knowledge recall as
      measured by RT difference score. Relative to non-feedback learning, the
      introduction of feedback during sequence learning improved subsequent sequence
      knowledge recall indexed by RT difference score, in both real and sham
      stimulation groups and feedback reversed the RT difference score based sequence
      knowledge recall impairment from real cTBS that we observed in the non-feedback
      learning condition. Only the real cTBS group in the non-feedback condition showed
      no evidence of explicit sequence knowledge when tested at the end of the study.
      Feedback improves recall of implicit and explicit motor sequence knowledge and
      can protect sequence knowledge against the effect of M1 inhibition. Adding
      feedback and monetary reward/punishment to motor skill learning may help overcome
      retention impairments or accelerate training in clinical and other settings. 

PMID- 26204233
TI  - Novel Resveratrol-Based Aspirin Prodrugs: Synthesis, Metabolism, and Anticancer
      Activity.
AB  - Regular aspirin use has been convincingly shown to reduce the risk of colorectal
      cancer. However, long-term use of aspirin leads to gastrotoxicity. Herein, we
      designed and synthesized a novel class of resveratrol-based aspirin prodrugs to
      simultaneously release aspirin and resveratrol to attenuate the side effects
      caused by aspirin. Prodrug RAH exerted enhanced anticancer activities which are
      better than a physical mixture of aspirin and resveratrol as well as each
      individually. Metabolism of RAH in mice showed that the majority of RAH is
      decomposed to release resveratrol and aspirin or salicylic acid either in the
      intestine or after absorption. Mechanistic studies demonstrate RAH inhibits cell
      cycle arrest through downregulation of cyclins and induces apoptosis by
      activation of caspase-3 in cancer cells. These findings highlighted the improved
      anticancer properties of resveratrol-based aspirin prodrugs. RAH may represent
      novel and safe alternatives of aspirin for the purpose of daily use in the
      future. 

PMID- 26204234
TI  - Quantitative profiling of polar primary metabolites of two chickpea cultivars
      with contrasting responses to salinity.
AB  - This study reports a GC-QqQ-MS method for the quantification of forty-eight
      primary metabolites from four major classes (sugars, sugar acids, sugar
      phosphates, and organic acids) which can be applied to a number of biological
      systems. The method was validated in terms of linearity, reproducibility and
      recovery, using both calibration standards and real samples. Additionally, twenty
      eight biogenic amines and amino acids were quantified using an established LC-QqQ
      MS method. Both GC-QqQ-MS and LC-QqQ-MS quantitative methods were applied to
      plant extracts from flower and pod tissue of two chickpea (Cicer arietinum L.)
      cultivars differing in their ability to tolerate salinity, which were grown under
      control and salt-treated conditions. Statistical analysis was applied to the data
      sets using the absolute concentrations of metabolites to investigate the
      differences in metabolite profiles between the different cultivars, plant
      tissues, and treatments. The method is a significant improvement of present
      methodology for quantitative GC-MS metabolite profiling of organic acids and
      sugars, and provides new insights of chickpea metabolic responses to salinity
      stress. It is applicable to the analysis of dynamic changes in endogenous
      concentrations of polar primary metabolites to study metabolic responses to
      environmental stresses in complex biological tissues. 

PMID- 26204235
TI  - Identification and characterization of tetracycline resistance in Lactococcus
      lactis isolated from Polish raw milk and fermented artisanal products.
AB  - To assess the occurrence of antibiotic-resistant Lactic Acid Bacteria (LAB) in
      Polish raw milk and fermented artisanal products, a collection comprising 500
      isolates from these products was screened. Among these isolates, six strains
      (IBB28, IBB160, IBB161, IBB224, IBB477 and IBB487) resistant to tetracycline were
      identified. The strains showing atypical tetracycline resistance were classified
      as Lactococcus lactis: three of them were identified as L. lactis subsp. cremoris
      (IBB224, IBB477 and IBB487) and the other three (IBB28, IBB160, IBB161) were
      identified as L. lactis subsp. lactis. The mechanism involving Ribosomal
      Protection Proteins (RPP) was identified as responsible for tetracycline
      resistance. Three of the tested strains (IBB28, IBB160 and IBB224) had genes
      encoding the TetS protein, whereas the remaining three (IBB161, IBB477 and
      IBB487) expressed TetM. The results also demonstrated that the genes encoding
      these proteins were located on genetic mobile elements. The tet(S) gene was found
      to be located on plasmids, whereas tet(M) was found within the Tn916 transposon. 

PMID- 26204237
TI  - A van der Waals Density Functional Investigation on the Improved Adsorption
      Properties of NO on the Rhn/MgO (100) Interface.
AB  - Using spin-polarized density functional theory calculations, we have studied the
      interaction and morphology of small Rhn clusters (n<=5) deposited on a MgO (100)
      surface, as well as the ability of Rhn/MgO systems to trap NO molecules. We show
      that Rhn clusters can tightly adhere to a MgO (100) surface because of
      hybridization of O 2p and Rh 4d orbitals. The most energetically preferred
      structure for each adsorbed Rhn cluster looks similar to the structure of the
      isolated cluster, except for an increment in the length of base edge(s) close to
      the substrate. We find that the Rhn/MgO system exhibits a much stronger ability
      to trap NO, especially for Rh2 and Rh4 clusters, than do the bare Rhn clusters.
      The hybridization of N 2p and Rh 4d orbitals is responsible for the strong
      adsorption of NO on Rhn/MgO. This can be explained by the increased Rh-Rh bond
      length that results in a decrease in the effective coordination number, and the
      presence of extra electrons obtained from the substrate, causing the N and O
      atoms to bond strongly to the Rh atoms, which in turn weakens the N-O molecular
      interaction. Additionally, binding to NO induces a reduction in the total
      magnetic moment of the Rhn/MgO system. Thus, putting Rhn on the MgO (100) surface
      can decrease competition between bonding and magnetism. However, whether it can
      be related to improve trapping of NO deserves further investigations.

PMID- 26204236
TI  - MI-PVT: A Tool for Visualizing the Chromosome-Centric Human Proteome.
AB  - We have developed the web-based Michigan Proteome Visualization Tool (MI-PVT) to
      visualize and compare protein expression and isoform-level function across human
      chromosomes and tissues (http://guanlab.ccmb.med.umich.edu/mipvt). As proof of
      principle, we have populated the tool with Human Proteome Map (HPM) data. We were
      able to observe many biologically interesting features. From the vantage point of
      our chromosome 17 team, for example, we found more than 300 proteins from
      chromosome 17 expressed in each of the 30 tissues and cell types studied, with
      the highest number of expressed proteins being 685 in testis. Comparisons of
      expression levels across tissues showed low numbers of proteins expressed in
      esophagus, but esophagus had 12 cytoskeletal proteins coded on chromosome 17 with
      very high expression (>1000 spectral counts). This customized MI-PVT should be
      helpful for biologists to browse and study specific proteins and protein data
      sets across tissues and chromosomes. Users can upload any data of interest in MI
      PVT for visualization. Our aim is to integrate extensive mass-spectrometric
      proteomic data into the tool to facilitate finding chromosome-centric protein
      expression and correlation across tissues.

PMID- 26204238
TI  - Stereoselective ZrCl4-Catalyzed Mannich-type Reaction of beta-Keto Esters with
      Chiral Trifluoromethyl Aldimines.
AB  - A method for the synthesis of fluorinated beta'-amino beta-dicarbonyl compounds
      using a Zr-catalyzed Mannich-type reaction has been developed, starting from N
      protected trifluoromethyl aldimines and cyclic or acyclic beta-keto esters
      bearing different ester residues. The in situ generated metallic complex reacted
      with optically pure trifluoromethyl aldimine derived from (R)-alpha
      methylbenzylamine, giving a highly diastereoselective asymmetric Mannich-type
      addition with formation of a chiral quaternary center. The absolute configuration
      at the new chiral centers was assigned through two-dimensional nuclear Overhauser
      effect spectroscopic analysis coupled with computational studies. 

PMID- 26204239
TI  - Electron Dynamics and IR Peak Coalescence in Bridged Mixed Valence Dimers Studied
      by Ultrafast 2D-IR Spectroscopy.
AB  - Dynamic IR peak coalescence and simulations based on the optical Bloch equations
      have been used previously to predict the rates of intramolecular electron
      transfer in a group of bridged mixed valence dimers of the type
      [Ru3(O)(OAc)6(CO)L]-BL-[Ru3(O) (OAc)6(CO)L]. However, limitations of the Bloch
      equations for the analysis of dynamical coalescence in vibrational spectra have
      been described. We have used ultrafast 2D-IR spectroscopy to investigate the
      vibrational dynamics of the CO spectator ligands of several dimers in the group.
      These experiments reveal that no electron site exchange occurs on the time scale
      required to explain the observed peak coalescence. The high variability in FTIR
      peak shapes for these mixed valence systems is suggested to be the result of
      fluctuations in the charge distributions at each metal cluster within a single
      well potential energy surface, rather than the previous model of two-site
      exchange. 

PMID- 26204240
TI  - Excited-State Photolytic Mechanism of Cyclopentene Containing a Group 14 Element:
      An MP2-CAS//CASSCF Study.
AB  - The potential energy surfaces corresponding to the photolytic reactions of 1,2
      dimethyl-cyclopentene, 3,4-dimethyl-silacyclopent-3-ene, and 3,4-dimethyl
      germacyclopent-3-ene were investigated by employing the CAS(6,6)/6-311G(d) and
      MP2-CAS-(6,6)/6-311++G(3df,3pd)//CAS(6,6)/6-311G(d) methods. Also, six kinds of
      substituted germacyclopent-3-ene were used as model reactants by way of the
      CASSCF and MP2-CAS methods to study their photolytic mechanisms. The theoretical
      findings indicate that the photolysis of the above reactants all adopt the same
      reaction path as follows: reactant -> Franck-Condon region -> conical
      intersection -> germylene and 1,3-butadiene. However, the theoretical results
      demonstrate that no photolysis ((1)(pi ->pi*)) can be observed in the 1,2
      dimethyl-cyclopentene system. Above all, the theoretical investigations strongly
      suggest that both steric effects, originating from the bulky substituents, and
      the atomic radius of the group 14 element (C, Si, and Ge) play a crucial role in
      determining the cis/trans selectivity of the conformation of 1,3-butadiene during
      their photolytic reactions. 

PMID- 26204241
TI  - Carbamazepine versus phenobarbitone monotherapy for epilepsy: an individual
      participant data review.
AB  - BACKGROUND: This is an updated version of the original Cochrane review published
      in Issue 1, 2003, of the Cochrane Database of Systematic Reviews.Epilepsy is a
      common neurological condition in which abnormal electrical discharges from the
      brain cause recurrent unprovoked seizures. It is believed that with effective
      drug treatment, up to 70% of individuals with active epilepsy have the potential
      to become seizure-free and go into long-term remission shortly after starting
      drug therapy with a single antiepileptic drug (AED) in monotherapy.Worldwide,
      carbamazepine (CBZ) and phenobarbitone (PB) are commonly used broad-spectrum
      antiepileptic drugs, suitable for most epileptic seizure types. Carbamazepine is
      a current first-line treatment for partial onset seizures in the USA and Europe.
      Phenobarbitone is no longer considered a first-line treatment because of concerns
      over associated adverse events, particularly documented behavioural adverse
      events in children treated with the drug. However, PB is still commonly used in
      low- and middle-income countries because of its low cost. No consistent
      differences in efficacy have been found between CBZ and PB in individual trials;
      however, the confidence intervals generated by these studies are wide, and
      therefore, synthesising the data of the individual trials may show differences in
      efficacy. OBJECTIVES: To review the time to withdrawal, remission, and first
      seizure of CBZ compared with PB when used as monotherapy in people with partial
      onset seizures (simple or complex partial and secondarily generalised) or
      generalised onset tonic-clonic seizures (with or without other generalised
      seizure types). SEARCH METHODS: We searched the following databases up to
      September 2014: the Cochrane Epilepsy Group Specialized Register, the Cochrane
      Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (2014,
      Issue 8), MEDLINE (from 1946), Scopus (from 1823), the US National Institutes of
      Health Ongoing Trials Register (www.clinicaltrials.gov), and the World Health
      Organization International Clinical Trials Registry platform (WHO ICTRP). We
      handsearched relevant journals and contacted pharmaceutical companies, original
      trial investigators, and experts in the field. SELECTION CRITERIA: Randomised
      controlled trials in children or adults with partial onset seizures or
      generalised onset tonic-clonic seizures with a comparison of CBZ monotherapy
      versus PB monotherapy. DATA COLLECTION AND ANALYSIS: This was an individual
      participant data (IPD) review. Our primary outcome was 'Time to withdrawal of
      allocated treatment', and our secondary outcomes were 'Time to 12-month
      remission', 'Time to 6-month remission', and 'Time to first seizure
      postrandomisation'. We used Cox proportional hazards regression models to obtain
      study-specific estimates of hazard ratios (HRs) with 95% confidence intervals
      (CIs), with the generic inverse variance method used to obtain the overall pooled
      HR and 95% CI. MAIN RESULTS: Individual participant data were available for 836
      participants out of 1455 eligible individuals from 6 out of 13 trials, 57% of the
      potential data. For remission outcomes, HR > 1 indicated an advantage for PB, and
      for first seizure and withdrawal outcomes, HR > 1 indicated an advantage for
      CBZ.The main overall results (pooled HR adjusted for seizure type, 95% CI) were
      HR 1.50 for time to withdrawal of allocated treatment (95% CI 1.15 to 1.95, P =
      0.003); HR 0.93 for time to 12-month remission (95% CI 0.72 to 1.20, P = 0.57);
      HR 0.99 for time to 6-month remission (95% CI 0.80 to 1.23, P = 0.95); and HR
      0.87 for time to first seizure (95% CI 0.72 to 1.06, P = 0.18). Results suggest
      an advantage for CBZ over PB in terms of time to treatment withdrawal and no
      statistically significant evidence between the drugs for the other outcomes. We
      found evidence of a statistically significant interaction between treatment
      effect and seizure type for time to first seizure recurrence (Chi2 test for
      subgroup differences P = 0.03), where PB was favoured for partial onset seizures
      (HR 0.76, 95% CI 0.60 to 0.96, P = 0.02) and CBZ was favoured for generalised
      onset seizures (HR 1.23, 95% CI 0.88 to 1.77, P = 0.27). However, methodological
      quality of the included studies was variable, with 10 out of the 13 included
      studies (4 out of 6 studies contributing IPD) judged as high risk of bias for at
      least 1 methodological aspect, leading to variable individual study results and
      therefore heterogeneity in the analyses of this review. We conducted sensitivity
      analyses to examine the impact of poor methodological aspects where possible.
      AUTHORS' CONCLUSIONS: Overall, we found evidence suggestive of an advantage for
      CBZ in terms of drug effectiveness compared with PB (retention of the drug in
      terms of seizure control and adverse events) and evidence of an association
      between treatment effect and seizure type for time to first seizure recurrence
      (PB favoured for partial seizures and CBZ favoured for generalised seizures).
      Given the varying quality of studies included in this review and the impact of
      poor methodological quality on individual study results (and therefore
      variability (heterogeneity) present in the analysis within this review), we
      recommend caution when interpreting the results of this review and do not
      recommend that the results of this review alone should be used in choosing
      between CBZ and PB. We recommend that future trials should be designed to the
      highest quality possible with considerations for allocation concealment and
      masking, choice of population, choice of outcomes and analysis, and presentation
      of results.

PMID- 26204242
TI  - Tunable Cyclopentane-1,3-diyls Generated by Insertion of Isonitriles into
      Diphosphadiazanediyls.
AB  - Diphosphadiazanediyl ([P(MU-NTer)]2, 1) is known to readily react with small
      molecules bearing multiple bonds to give [2.1.1]bicyclic species. On the
      contrary, in the reaction of isonitriles with 1, planar five-membered
      heterocycles (3) with biradical character are formed by insertion of the carbon
      atom into one P-N bond. Under irradiation, heterocyclic biradicaloids 3 are shown
      to generate housane-type [2.1.0]bicyclopentanes by transannular bond formation.
      However, these housane species thermally equilibrate, reforming the open-shell
      singlet cyclopentanediyl. The biradical character of 3 indicates high reactivity
      which is further demonstrated in the activation of small molecules bearing
      multiple bonds leading to [2.2.1]bicyclic heterocycles. Depending on the
      substituent of the isonitrile, the reaction with a second equivalent of
      isonitrile is also observed for smaller substituents. By employing suitable
      diisonitriles, even the catenation of two open-shell singlet cyclopentane-1,3
      diyls is achieved. CASSCF(6,6) computations revealed biradical character for 3
      ranging between 26 and 27%. 

PMID- 26204243
TI  - Structural characterisation of printable noble metal/poly(vinyl-alcohol)
      nanocomposites for optical applications.
AB  - In order to enable exploitation of noble metal/poly(vinyl-alcohol) nanocomposites
      for device fabrication, solutions of poly(vinyl-alcohol) suitable for piezo
      driven inkjet printing techniques are identified and discussed in terms of their
      material properties. The printable poly(vinyl-alcohol) medium is then exploited
      as a host material through the formation of silver or gold nanoparticles in order
      to create nanocomposites that exhibit a surface plasmon resonance behaviour
      associated with the small metallic inclusions. To mitigate some of the material
      redistribution effects associated with the drying of printed droplets containing
      finely divided materials, the metallic nanoparticles are formed after the
      printing and drying process is completed, by way of an in situ reduction of an
      appropriate metal salt by the poly(vinyl-alcohol)-host matrix itself, which takes
      place at modest temperatures compatible with most substrate materials. An obvious
      application for such nanocomposites is in optical elements whereby the surface
      plasmon resonance associated with the metal is the functional aspect of devices
      such as sensors or active optical elements. High Resolution Transmission Electron
      Microscopy was used to examine the dimensions, distribution, morphology and
      crystal structure of the silver and gold nanoparticles in detail allowing
      discussion of their suitability for these applications and what further
      optimisation may be necessary to adequately control their formation. 

PMID- 26204244
TI  - Bacterial Community Profiling of Plastic Litter in the Belgian Part of the North
      Sea.
AB  - Bacterial colonization of marine plastic litter (MPL) is known for over four
      decades. Still, only a few studies on the plastic colonization process and its
      influencing factors are reported. In this study, seafloor MPL was sampled at
      different locations across the Belgian part of the North Sea to study bacterial
      community structure using 16S metabarcoding. These marine plastic bacterial
      communities were compared with those of sediment and seawater, and resin pellets
      sampled on the beach, to investigate the origin and uniqueness of plastic
      bacterial communities. Plastics display great variation of bacterial community
      composition, while each showed significant differences from those of sediment and
      seawater, indicating that plastics represent a distinct environmental niche.
      Various environmental factors correlate with the diversity of MPL bacterial
      composition across plastics. In addition, intrinsic plastic-related factors such
      as pigment content may contribute to the differences in bacterial colonization.
      Furthermore, the differential abundance of known primary and secondary colonizers
      across the various plastics may indicate different stages of bacterial
      colonization, and may confound comparisons of free-floating plastics. Our studies
      provide insights in the factors that shape plastic bacterial colonization and
      shed light on the possible role of plastic as transport vehicle for bacteria
      through the aquatic environment.

PMID- 26204245
TI  - The effects of graphene oxide on green algae Raphidocelis subcapitata.
AB  - Graphene represents a new class of nanomaterials that has attracted great
      interest due to its unique electrical, thermal, and mechanical properties. Once
      disposed in the environment, graphene can interact with biological systems and is
      expected to exhibit toxicological effects. The ecotoxicity of graphene and its
      derivatives, viz.: graphene oxide (GO) depends on their physicochemical
      properties, including purity, diameter, length, surface charge, functionalization
      and aggregation state. In this study we evaluated the effects of graphene oxide
      (GO) on green algae Raphidocelis subcapitata. The algae were exposed to different
      concentrations of GO pre-equilibrated for 24h with oligotrophic freshwater medium
      (20ml) during incubation in a growth chamber under controlled conditions:
      120MUEm(-2)s(-1) illumination; 12:12h light dark cycle and constant temperature
      of 22+/-2 degrees C. Algal growth was monitored daily for 96h by direct cell
      counting. Reactive oxygen species level (ROS), membrane damage (cell viability)
      and autofluorescence (chl-a fluorescence) were evaluated using fluorescent
      staining and further analyzed by flow cytometry. The toxic effects from GO, as
      observed in algal density and autofluorescence, started at concentrations from 20
      and 10MUgmL(-1), respectively. Such toxicity is probably the result of ROS
      generation and membrane damage (cell viability). The shading effect caused by GO
      agglomeration in culture medium may also contribute to reduce algal density. The
      results reported here provide knowledge regarding the GO toxicity on green algae,
      contributing to a better understanding of its environmental behavior and impacts.

PMID- 26204246
TI  - (1)H NMR-based metabolic profiling of liver in chronic unpredictable mild stress
      rats with genipin treatment.
AB  - Genipin, a hydrolyzed metabolite of geniposide extracted from the fruit of
      Gardenia jasminoides Ellis, has shown promise in alleviating depressive symptoms,
      however, the antidepressant mechanism of genipin remains unclear and
      incomprehensive. In this study, the metabolic profiles of aqueous and lipophilic
      extracts in liver of the chronic unpredictable mild stress (CUMS)-induced rat
      with genipin treatment were investigated using proton nuclear magnetic resonance
      ((1)H NMR) spectroscopy coupled with multivariate data analysis. Significant
      differences in the metabolic profiles of rats in the CUMS model group (MS) and
      the control group (NS) were observed with metabolic effects including decreasing
      in choline, glycerol and glycogen, increasing in lactate, alanine and succinate,
      and a disordered lipid metabolism, while the moderate dose (50mg/kg) of genipin
      could significantly regulate the concentrations of glycerol, lactate, alanine,
      succinate and the lipid to their normal levels. These biomakers were involved in
      metabolism pathways such as glycolysis/gluconeogensis, tricarboxylic acid (TCA)
      cycle and lipid metabolism, which may be helpful for understanding of
      antidepressant mechanism of genipin.

PMID- 26204247
TI  - Mild hypodontia is associated with smaller tooth dimensions and cusp numbers than
      in controls.
AB  - OBJECTIVE: The associations seen clinically between variations in tooth number,
      size and shape reflect the repetitive genetic interactions occurring between the
      epithelium and mesenchyme during the initiation and morphogenetic stages of the
      Complex Adaptive System that is dental development. The aim of this study was to
      investigate the clinical relationship further by comparing multiple crown
      parameters, including cusp numbers, between patients with mild hypodontia and
      controls in a Romanian sample. DESIGN: Digital images of dental casts of the
      permanent dentition from 28 patients with mild hypodontia and 28 controls were
      used. Measurements from the vestibular and occlusal surfaces were performed using
      a 2D image analysis method and cusps, including the Carabelli trait, were
      counted. Two-way analysis of variance was performed. RESULTS: The dimensions of
      the mild hypodontia group had smaller values than the controls, with many
      measurements being significantly different (significance values varied from
      p=0.049 to p=0.001). The most affected regions were the upper and lower anterior
      region in both sexes. Mesio-distal, bucco-lingual and occlusal area and perimeter
      dimensions were affected. Females from the hypodontia group had significantly
      less tricuspidated lower premolars when compared with the control group.
      Carabelli cusps were present in the hypodontia group less frequently, the
      difference being highly significant (p=0.0002) in women. CONCLUSIONS: The
      hypodontia patients presented with reduced crown dimensions and shape compared
      with controls. This is the first published study to demonstrate smaller cusp
      numbers in patients with hypodontia than in controls. The findings are compatible
      with a model of dental development as a Complex Adaptive System incorporating
      associations between tooth number, size and shape.

PMID- 26204248
TI  - Highly Enantioselective Cascade Reaction Catalyzed by Squaramides: the Synthesis
      of CF3-Containing Chromanes.
AB  - A catalytic asymmetric method for the synthesis of 2-CF3 chromanes has been
      described. Generally, the squaramide-catalyzed cascade reaction of 2
      hydroxychalcones with beta-CF3-nitroalkenes gave the CF3-containing heterocyclic
      compounds bearing three contiguous stereogenic centers in excellent yields,
      diastereoselectivities, and enantioselectivities. 

PMID- 26204250
TI  - Light, lipids and photoreceptor survival: live or let die?
AB  - Due to its constant exposure to light and its high oxygen consumption the retina
      is highly sensitive to oxidative damage, which is a common factor in inducing the
      death of photoreceptors after light damage or in inherited retinal degenerations.
      The high content of docosahexaenoic acid (DHA), the major polyunsaturated fatty
      acid in the retina, has been suggested to contribute to this sensitivity. DHA is
      crucial for developing and preserving normal visual function. However, further
      roles of DHA in the retina are still controversial. Current data support that it
      can tilt the scale either towards degeneration or survival of retinal cells. DHA
      peroxidation products can be deleterious to the retina and might lead to retinal
      degeneration. However, DHA has also been shown to act as, or to be the source of,
      a survival molecule that protects photoreceptors and retinal pigment epithelium
      cells from oxidative damage. We have established that DHA protects photoreceptors
      from oxidative stress-induced apoptosis and promotes their differentiation in
      vitro. DHA activates the retinoid X receptor (RXR) and the ERK/MAPK pathway, thus
      regulating the expression of anti and pro-apoptotic proteins. It also
      orchestrates a diversity of signaling pathways, modulating enzymatic pathways
      that control the sphingolipid metabolism and activate antioxidant defense
      mechanisms to promote photoreceptor survival and development. A deeper
      comprehension of DHA signaling pathways and context-dependent behavior is
      required to understand its dual functions in retinal physiology. 

PMID- 26204251
TI  - Synthesis of functional xLayMn/KIT-6 and features in hot coal gas
      desulphurization.
AB  - To enhance the stability of sorbents during continuous desulphurization
      regeneration cycles, KIT-6 with 3D pore channels was used as a support for the
      sorbents. A series of mesoporous xLayMn/KIT-6 sorbents with different La/Mn
      atomic ratios were fabricated using a sol-gel method and their desulphurization
      properties of hot coal gas were investigated at 700-850  degrees C. 3La97Mn/KIT-6
      performed the best at 800  degrees C with a breakthrough sulphur capacity of
      11.56 g sulphur per 100 g sorbent. The eight successive desulphurization (800 
      degrees C)-regeneration (600  degrees C) cycles revealed that 3La97Mn/KIT-6 with
      endurable regeneration abilities could retain 80% of the initial sulphur
      capacity. It indicated a better desulphurization performance compared to pure
      3La97Mn and 3La97Mn/MCM-41. The fresh and used xLayMn/KIT-6 sorbents were
      characterized by means of BET, XRD, HRTEM, XPS and H2-TPR techniques. The XRD
      patterns and HRTEM images of fresh and used 3La97Mn/KIT-6 verified that the
      utilization of KIT-6 effectively suppressed the aggregation of Mn2O3 particles
      and improved the stability of the sorbent. 

PMID- 26204253
TI  - Ebola and the eye.

PMID- 26204252
TI  - VS-5584, a Novel PI3K-mTOR Dual Inhibitor, Inhibits Melanoma Cell Growth In Vitro
      and In Vivo.
AB  - Melanomas cause over 76% of skin cancer deaths annually. Phosphatidylinositol 3
      kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is
      important for melanoma initiation and progression. In the current study, we
      evaluated the potential anti-melanoma effect of VS-5584, a novel and highly
      potent PI3K-mTOR dual inhibitor. We demonstrated that VS-5584 potently inhibited
      survival and proliferation of established (A375, A-2058 and SK-MEL-3 lines) and
      primary human melanoma cells, but was non-cytotoxic to non-cancerous human skin
      keratinocytes and B10BR murine melanocytes. At the meantime, VS-5584 induced
      caspase-dependent apoptotic death in melanoma cells, and its cytotoxicity was
      alleviated by the caspase inhibitors. At the molecular level, VS-5584 blocked AKT
      mTOR activation and downregulated cyclin D1 expression in melanoma cells, while
      the expressions of Bcl-xL and Bcl-2 were not affected by VS-5584 treatment. On
      the other hand, a BH-3 mimetic Bcl-xL/Bcl-2 inhibitor ABT-737, as well as siRNA
      mediated knockdown of Bcl-xL or Bcl-2, enhanced the activity of VS-5584 in
      melanoma cells. In vivo, oral administration of VS-5584 suppressed A375 melanoma
      xenograft growth in nude mice, and its activity was further enhanced by co
      administration of ABT-737. These results provide the rationale for the clinical
      assessment of VS-5584 in melanoma patients and development of ABT-737 and other
      Bcl-xL/Bcl-2 inhibitors as the possible adjuvants. 

PMID- 26204254
TI  - Personality selection: An argument against the homogenisation of medical
      students.

PMID- 26204249
TI  - Mass spectrometry for the assessment of the occurrence and biological
      consequences of DNA adducts.
AB  - Exogenous and endogenous sources of chemical species can react, directly or after
      metabolic activation, with DNA to yield DNA adducts. If not repaired, DNA adducts
      may compromise cellular functions by blocking DNA replication and/or inducing
      mutations. Unambiguous identification of the structures and accurate measurements
      of the levels of DNA adducts in cellular and tissue DNA constitute the first and
      important step towards understanding the biological consequences of these
      adducts. The advances in mass spectrometry (MS) instrumentation in the past 2-3
      decades have rendered MS an important tool for structure elucidation,
      quantification, and revelation of the biological consequences of DNA adducts. In
      this review, we summarized the development of MS techniques on these fronts for
      DNA adduct analysis. We placed our emphasis of discussion on sample preparation,
      the combination of MS with gas chromatography- or liquid chromatography (LC)
      based separation techniques for the quantitative measurement of DNA adducts, and
      the use of LC-MS along with molecular biology tools for understanding the human
      health consequences of DNA adducts. The applications of mass spectrometry-based
      DNA adduct analysis for predicting the therapeutic outcome of anti-cancer agents,
      for monitoring the human exposure to endogenous and environmental genotoxic
      agents, and for DNA repair studies were also discussed. 

PMID- 26204255
TI  - Creation of a mobile rural workforce following undergraduate longitudinal rural
      immersion.
AB  - BACKGROUND: This study followed the workforce choices of 10-years of graduates
      from a longitudinal rural immersion programme, which involved living for one
      academic year in a rural location as a medical student. The Rural Clinical School
      of Western Australia is a whole-of-state Rural Clinical School partnership
      involving two medical schools and fourteen rural/remote towns. METHOD: For this
      longitudinal cohort study, all consenting graduates were contacted annually after
      graduation, with the outcome measure being rural work location (defined by the
      Australian Standard Geographical Classification -Remoteness Area) of any
      duration. RESULTS: There were 417 consenting graduates. Between 16 and 50% of
      contacted alumni worked rurally for a period of each post-graduate year.
      Aggregated over time, the majority took up to 30% of their postgraduate training
      rurally. There was considerable movement in and out of rural work. About 17% of
      contacted and practicing graduates were working full time rurally at the 2013
      contact point. The majority remained in their state of training. The majority
      identified with GP and other rural-related colleges, and College-affiliation
      predicted amount of rural training time. Entry into rural work was equivalent for
      urban-origin and rural origin alumni, suggesting one year of RCS is sufficient to
      convert commitment to rural work. CONCLUSION: Undergraduate rural immersion is
      sufficient to create a graduate rural workforce that is far more mobile that was
      previously appreciated.

PMID- 26204256
TI  - Diadenosine 5', 5'''-P(1),P(4)-tetraphosphate (Ap4A) is synthesized in response
      to DNA damage and inhibits the initiation of DNA replication.
AB  - The level of intracellular diadenosine 5', 5'''-P(1),P(4)-tetraphosphate (Ap4A)
      increases several fold in mammalian cells treated with non-cytotoxic doses of
      interstrand DNA-crosslinking agents such as mitomycin C. It is also increased in
      cells lacking DNA repair proteins including XRCC1, PARP1, APTX and FANCG, while
      >50-fold increases (up to around 25 MUM) are achieved in repair mutants exposed
      to mitomycin C. Part of this induced Ap4A is converted into novel derivatives,
      identified as mono- and di-ADP-ribosylated Ap4A. Gene knockout experiments
      suggest that DNA ligase III is primarily responsible for the synthesis of damage
      induced Ap4A and that PARP1 and PARP2 can both catalyze its ADP-ribosylation.
      Degradative proteins such as aprataxin may also contribute to the increase. Using
      a cell-free replication system, Ap4A was found to cause a marked inhibition of
      the initiation of DNA replicons, while elongation was unaffected. Maximum
      inhibition of 70-80% was achieved with 20 MUM Ap4A. Ap3A, Ap5A, Gp4G and ADP
      ribosylated Ap4A were without effect. It is proposed that Ap4A acts as an
      important inducible ligand in the DNA damage response to prevent the replication
      of damaged DNA.

PMID- 26204257
TI  - Enhanced second harmonic generation of MoS2 layers on a thin gold film.
AB  - The linear and nonlinear optical properties of thin MoS2 layers exfoliated on an
      Au/SiO2 substrate were investigated both numerically and experimentally. It was
      found that the MoS2 layers with different thicknesses exhibited different colors
      on the gold film. The reflection spectra of the MoS2 layers with different
      thicknesses were calculated by using the finite-difference time-domain technique
      and the corresponding chromaticity coordinates were derived. The electric field
      enhancement factors at both the fundamental light and the second harmonic were
      calculated and the enhancement factors for second harmonic generation (SHG) were
      estimated for the MoS2 layers with different thicknesses. Different from the MoS2
      layers on a SiO2/Si substrate where the maximum SHG was observed in the single
      layer MoS2, the maximum SHG was achieved in the 17 nm-thick MoS2 layer on the
      Au/SiO2 substrate. As compared with the MoS2 layers on the SiO2/Si substrate, a
      significant enhancement in SHG was found for the MoS2 layers on the Au/SiO2
      substrate due to the strong localization of the electric field. More
      interestingly, it was demonstrated experimentally that optical data storage can
      be realized by modifying the SHG intensity of a MoS2 layer through thinning its
      thickness. 

PMID- 26204258
TI  - Preoperative Renal Volume: A Surrogate Measure for Radical Nephrectomy-Induced
      Chronic Kidney Disease.
AB  - OBJECTIVES: Surgically induced chronic kidney disease (CKD) has been found to
      have less impact on survival as well as function when compared to medical causes
      for CKD. The aim of this study is to evaluate whether preoperative remaining
      kidney volume correlates with renal function after nephrectomy, which represents
      an individual's renal reserve before surgically induced CKD. METHODS: A
      retrospective review of 75 consecutive patients (29.3% females) who underwent
      radical nephrectomy (RN) (2000-2010) was performed. Normal side kidney
      parenchyma, excluding renal vessels and central sinus fat, was manually outlined
      in each transverse slice of CT image and multiplied by slice thickness to
      calculate volume. Estimated glomerular filtration rate (eGFR) was determined
      using the Modification of Diet in Renal Disease equation. CKD is defined as eGFR
      < 60 mL/min/1.73 m(2). RESULTS: Mean preoperative normal kidney parenchymal
      volume (mean age 55 [SD 13] years) is 150.7 (SD 36.4) mL. Over median follow-up
      of 36 months postsurgery, progression to CKD occurred in 42.6% (n = 32) of
      patients. On multivariable analysis, preoperative eGFR and preoperative renal
      volume <144 mL are independent predictors for postoperative CKD. On Kaplan-Meier
      analysis, median time to reach CKD postnephrectomy is 12.7 (range 0.03-43.66)
      months for renal volume <144 mL but not achieved if renal volume is >144 mL.
      CONCLUSIONS: Normal kidney parenchymal volume and preoperative eGFR are
      independent predictive factors for postoperative CKD after RN and may represent
      renal reserve for both surgically and medically induced CKD, respectively.
      Preoperative remaining kidney volume may be an adjunct representation of renal
      reserve postsurgery and predict later renal function decline due to perioperative
      loss of nephrons.

PMID- 26204259
TI  - Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive
      Immunity and Control of West Nile Virus Infection.
AB  - Impaired immune responses in the elderly lead to reduced vaccine efficacy and
      increased susceptibility to viral infections. Although several groups have
      documented age-dependent defects in adaptive immune priming, the deficits that
      occur prior to antigen encounter remain largely unexplored. Herein, we identify
      novel mechanisms for compromised adaptive immunity that occurs with aging in the
      context of infection with West Nile virus (WNV), an encephalitic flavivirus that
      preferentially causes disease in the elderly. An impaired IgM and IgG response
      and enhanced vulnerability to WNV infection during aging was linked to delayed
      germinal center formation in the draining lymph node (DLN). Adoptive transfer
      studies and two-photon intravital microscopy revealed a decreased trafficking
      capacity of donor naive CD4+ T cells from old mice, which manifested as impaired
      T cell diapedesis at high endothelial venules and reduced cell motility within
      DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN
      within the first few days of WNV infection or antigen-adjuvant administration was
      diminished more generally in old mice and associated with a second aging-related
      defect in local cytokine and chemokine production. Thus, age-dependent cell
      intrinsic and environmental defects in the DLN result in delayed immune cell
      recruitment and antigen recognition. These deficits compromise priming of early
      adaptive immune responses and likely contribute to the susceptibility of old
      animals to acute WNV infection. 

PMID- 26204261
TI  - The Evolving Landscape of HER2 Targeting in Breast Cancer.
AB  - The development of human epidermal growth factor receptor 2 (HER2)-targeting
      agents for the treatment of HER2-amplified breast cancer has dramatically
      improved outcomes for patients with this disease. The value of HER2 as a
      therapeutic target encompasses 2 entirely different mechanistic dimensions. The
      first approach exploits the fact that HER2 is clearly a disease-driving oncogene
      to deliver HER2 kinase inhibitors, apparently a highly rational approach to the
      treatment of HER2-amplified cancers. However, the functionally relevant HER2-HER3
      complex has proven much more difficult to inhibit than had been anticipated, and
      because of its modest efficacy, the HER2 inhibitor lapatinib is currently used
      predominantly in combinations and in very advanced stages of disease. The second
      approach exploits the massive cell surface expression of HER2 and delivers of a
      variety of cytotoxic or immunologic effectors with great selectivity to these
      cancer cells. This approach has proven transformative, with 3 such drugs
      introduced into practice to date. The HER2-specific antibody trastuzumab, in
      combination with chemotherapy, has shown substantial effect in the management of
      HER2-amplifed breast cancer at all stages of disease and lines of therapy-and the
      addition of the second HER2 antibody pertuzumab substantially increases the
      magnitude of this effect in all of the contexts tested thus far. While the
      immunologic effectors stimulated by these naked HER2 antibodies provide only
      modest activity as monotherapy, the toxin-carrying antibody trastuzumab-emtansine
      provides substantial single-agent activity and is being developed for both early-
      and late-stage disease. The diverse mechanistic landscape afforded by the target
      HER2 has proven to be fertile ground for drug development, but it has also
      created complexity and misconception in understanding these agents' modes of
      action, undermining the development of clinically useful predictive biomarkers.
      This accounts for the failure of signaling-based biomarkers to predict clinical
      trastuzumab resistance and shifted the focus to markers of immunologic activity
      with greater success. The evolving world of HER2 targeting is reviewed herein. 

PMID- 26204260
TI  - Association of Psychological Disorders With 30-Day Readmission Rates in Patients
      With COPD.
AB  - BACKGROUND: There is a growing understanding of the prevalence and impact of
      psychological disorders on COPD. However, the role of these disorders in early
      readmission is unclear. METHODS: We analyzed data from 5% fee-for-service
      Medicare beneficiaries diagnosed with COPD (International Classification of
      Diseases, Ninth Revision code, 491.xx, 492.xx, 493.xx, and 496.xx) between 2001
      and 2011 who were hospitalized with a primary discharge diagnosis of COPD or a
      primary discharge diagnosis of respiratory failure (518.xx and 799.1) with
      secondary diagnosis of COPD. We hypothesized that such psychological disorders as
      depression, anxiety, psychosis, alcohol abuse, and drug abuse are independently
      associated with an increased risk of 30-day readmission in patients hospitalized
      for COPD. RESULTS: Between 2001 and 2011, 135,498 hospitalizations occurred for
      COPD in 80,088 fee-for-service Medicare beneficiaries. Of these, 30,218 (22.30%)
      patients had one or more psychological disorders. In multivariate analyses, odds
      of 30-day readmission were higher in patients with COPD who had depression (OR,
      1.34; 95% CI, 1.29-1.39), anxiety (OR, 1.43; 95% CI, 1.37-1.50), psychosis (OR,
      1.18; 95% CI, 1.10-1.27), alcohol abuse (OR, 1.30; 95% CI, 1.15-1.47), and drug
      abuse (OR, 1.29; 95% CI, 1.11-1.50) compared with those who did not have these
      disorders. These psychological disorders increased amount of variation in 30-day
      readmission attributed to patient characteristics by 37%. CONCLUSIONS:
      Psychological disorders like depression, anxiety, psychosis, alcohol abuse, and
      drug abuse are independently associated with higher all-cause 30-day readmission
      rates for Medicare beneficiaries with COPD.

PMID- 26204262
TI  - Modulation of Craving Related Brain Responses Using Real-Time fMRI in Patients
      with Alcohol Use Disorder.
AB  - LITERATURE: One prominent symptom in addiction disorders is the strong desire to
      consume a particular substance or to display a certain behaviour (craving).
      Especially the strong association between craving and the probability of relapse
      emphasises the importance of craving in the therapeutic process. Neuroimaging
      studies have shown that craving is associated with increased responses,
      predominantly in fronto-striatal areas. AIM AND METHODS: The aim of the present
      study is the modification of craving-related neuronal responses in patients with
      alcohol addiction using fMRI real-time neurofeedback. For that purpose, patients
      with alcohol use disorder and healthy controls participated once in neurofeedback
      training; during the sessions neuronal activity within an individualized cortical
      region of interest (ROI) (anterior cingulate cortex, insula, dorsolateral
      prefrontal cortex) was evaluated. In addition, variations regarding the
      connectivity between brain regions were assessed in the resting state. RESULTS
      AND DISCUSSION: The results showed a significant reduction of neuronal activity
      in patients at the end of the training compared to the beginning, especially in
      the anterior cingulate cortex, the insula, the inferior temporal gyrus and the
      medial frontal gyrus. Furthermore, the results show that patients were able to
      regulate their neuronal activities in the ROI, whereas healthy subjects achieved
      no significant reduction. However, there was a wide variability regarding the
      effects of the training within the group of patients. After the neurofeedback
      sessions, individual craving was slightly reduced compared to baseline. The
      results demonstrate that it seems feasible for patients with alcohol dependency
      to reduce their neuronal activity using rtfMRI neurofeedback. In addition, there
      is some evidence that craving can be influenced with the help of this technique.
      FUTURE PROSPECTS: In future, real-time fMRI might be a complementary
      neurophysiological-based strategy for the psychotherapy of patients with
      psychiatric or psychosomatic diseases. For that purpose, the stability of this
      effect and the generalizability needs to be assessed.

PMID- 26204263
TI  - Schistosoma mansoni Eggs in Spleen and Lungs, Mimicking Other Diseases.

PMID- 26204265
TI  - A Murine Myh6MerCreMer Knock-In Allele Specifically Mediates Temporal Genetic
      Deletion in Cardiomyocytes after Tamoxifen Induction.
AB  - A mouse model that mediates temporal, specific, and efficient myocardial deletion
      with Cre-LoxP technology will be a valuable tool to determine the function of
      genes during heart formation. Mhy6 encodes a cardiac muscle specific protein:
      alpha-myosin heavy chain. Here, we generated a new Myh6-MerCreMer
      (Myh6(MerCreMer/+)) inducible Cre knock-in mouse by inserting a MerCreMer
      cassette into the Myh6 start codon. By crossing knock-in mice with Rosa26
      reporter lines, we found the Myh6(MerCreMer/+) mice mediate complete Cre-LoxP
      recombination in cardiomyocytes after tamoxifen induction. X-gal staining and
      immunohistochemistry analysis revealed that Myh6-driven Cre recombinase was
      specifically activated in cardiomyocytes at embryonic and adult stages.
      Furthermore, echocardiography showed that Myh6(MerCreMer/+) mice maintained
      normal cardiac structure and function before and after tamoxifen administration.
      These results suggest that the new Myh6(MerCreMer/+) mouse can serve as a robust
      tool to dissect the roles of genes in heart development and function.
      Additionally, myocardial progeny during heart development and after cardiac
      injury can be traced using this mouse line.

PMID- 26204264
TI  - Spontaneous Activity Associated with Delusions of Schizophrenia in the Left
      Medial Superior Frontal Gyrus: A Resting-State fMRI Study.
AB  - Delusions of schizophrenia have been found to be associated with alterations of
      some brain regions in structure and task-induced activation. However, the
      relationship between spontaneously occurring symptoms and spontaneous brain
      activity remains unclear. In the current study, 14 schizophrenic patients with
      delusions and 14 healthy controls underwent a resting-state functional magnetic
      resonance imaging (RS-fMRI) scan. Patients with delusions of schizophrenia
      patients were rated with Positive and Negative Syndrome Scale (PANSS) and
      Characteristics of Delusional Rating Scale (CDRS). Regional homogeneity (ReHo)
      was calculated to measure the local synchronization of the spontaneous activity
      in a voxel-wise way. A two-sample t-test showed that ReHo of the right anterior
      cingulate gyrus and left medial superior frontal gyrus were higher in patients,
      and ReHo of the left superior occipital gyrus was lower, compared to healthy
      controls. Further, among patients, correlation analysis showed a significant
      difference between delusion scores of CRDS and ReHo of brain regions. ReHo of the
      left medial superior frontal gyrus was negatively correlated with patients' CDRS
      scores but not with delusional PANSS scores. These results suggested that altered
      local synchronization of spontaneous brain activity may be related to the
      pathophysiology of delusion in schizophrenia. 

PMID- 26204266
TI  - Self-Management Support Interventions for Stroke Survivors: A Systematic Meta
      Review.
AB  - BACKGROUND: There is considerable policy interest in promoting self-management in
      patients with long-term conditions, but it remains uncertain whether these
      interventions are effective in stroke patients. DESIGN: Systematic meta-review of
      the evidence for self-management support interventions with stroke survivors to
      inform provision of healthcare services. METHODS: We searched MEDLINE, EMBASE,
      CINAHL, PsychINFO, AMED, BNI, Database of Abstracts of Reviews for Effectiveness,
      and Cochrane Database of Systematic Reviews for systematic reviews of self
      management support interventions for stroke survivors. Quality was assessed using
      the R-AMSTAR tool, and data extracted using a customised data extraction form. We
      undertook a narrative synthesis of the reviews' findings. RESULTS: From 12,400
      titles we selected 13 systematic reviews (published 2003-2012) representing 101
      individual trials. Although the term 'self-management' was rarely used, key
      elements of self-management support such as goal setting, action planning, and
      problem solving were core components of therapy rehabilitation interventions. We
      found high quality evidence that supported self-management in the context of
      therapy rehabilitation delivered soon after the stroke event resulted in short
      term (< 1 year) improvements in basic and extended activities of daily living,
      and a reduction in poor outcomes (dependence/death). There is some evidence that
      rehabilitation and problem solving interventions facilitated reintegration into
      the community. CONCLUSIONS: Self-management terminology is rarely used in the
      context of stroke. However, therapy rehabilitation currently successfully
      delivers elements of self-management support to stroke survivors and their
      caregivers with improved outcomes. Future research should focus on managing the
      emotional, medical and social tasks of long-term survivorship.

PMID- 26204267
TI  - Control in the Rate-Determining Step Provides a Promising Strategy To Develop New
      Catalysts for CO2 Hydrogenation: A Local Pair Natural Orbital Coupled Cluster
      Theory Study.
AB  - The development of efficient catalysts with base metals for CO2 hydrogenation has
      always been a major thrust of interest. A series of experimental and theoretical
      work has revealed that the catalytic cycle typically involves two key steps,
      namely, base-promoted heterolytic H2 splitting and hydride transfer to CO2,
      either of which can be the rate-determining step (RDS) of the entire reaction. To
      explore the determining factor for the nature of RDS, we present herein a
      comparative mechanistic investigation on CO2 hydrogenation mediated by
      [M(H)(eta(2)-H2)(PP3(Ph))](n+) (M = Fe(II), Ru(II), and Co(III); PP3(Ph) = tris(2
      (diphenylphosphino)phenyl)phosphine) type complexes. In order to construct
      reliable free energy profiles, we used highly correlated wave function based ab
      initio methods of the coupled cluster type alongside the standard density
      functional theory. Our calculations demonstrate that the hydricity of the metal
      hydride intermediate generated by H2 splitting dictates the nature of the RDS for
      the Fe(II) and Co(III) systems, while the RDS for the Ru(II) catalyst appears to
      be ambiguous. CO2 hydrogenation catalyzed by the Fe(II) complex that possesses
      moderate hydricity traverses an H2-splitting RDS, whereas the RDS for the high
      hydricity Co(III) species is found to be the hydride transfer. Thus, our findings
      suggest that hydricity can be used as a practical guide in future catalyst
      design. Enhancing the electron-accepting ability of low-hydricity catalysts is
      likely to improve their catalytic performance, while increasing the electron
      donating ability of high-hydricity complexes may speed up CO2 conversion.
      Moreover, we also established the active roles of base NEt3 in directing the
      heterolytic H2 splitting and assisting product release through the formation of
      an acid-base complex. 

PMID- 26204269
TI  - Open Access and Institutional Repositories: How Should Subscription Journals
      Respond?

PMID- 26204268
TI  - Schizophrenia Related Variants in CACNA1C also Confer Risk of Autism.
AB  - Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with a
      strong genetic component. Many lines of evidence indicated that ASD shares common
      genetic variants with other psychiatric disorders (for example, schizophrenia).
      Previous studies detected that calcium channels are involved in the etiology of
      many psychiatric disorders including schizophrenia and autism. Significant
      association between CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C
      subunit) and schizophrenia was detected. Furthermore, rare mutation in CACNA1C is
      suggested to cause Timothy syndrome, a multisystem disorder including autism
      associated phenotype. However, there is no evidence for association between
      CACNA1C and autism in Chinese Han population. To investigate the association
      between single nucleotide polymorphisms (SNP) in CACNA1C and autism, we first
      performed a family-based association study between eighteen SNPs in CACNA1C and
      autism in 239 trios. All SNPs were genotyped by using Sequenom genotyping
      platform. Two SNPs (rs1006737 and rs4765905) have a trend of association with
      autism. To further confirm the association between these two SNPs with autism, we
      expanded the sample size to 553 trios by adding 314 trios. Association analyses
      for SNPs and haplotype were performed by using family-based association test
      (FBAT) and Haploview software. Permutation tests were used for multiple testing
      corrections of the haplotype analyses (n=10,000). The significance level for all
      statistical tests was two-tailed (p<0.05). The results demonstrated that G allele
      of rs1006737 and G allele of rs4765905 showed a preferential transmission to
      affected offspring in 553 trios (p=0.035). Haplotype analyses showed that two
      haplotypes constructed from rs1006737 and rs4765905 were significantly associated
      with autism (p=0.030, 0.023, respectively; Global p=0.046). These results were
      still significant after permutation correction (n=10,000, p=0.027). Our research
      suggests that CACNA1C might play a role in the genetic etiology of autism in
      Chinese Han population. 

PMID- 26204270
TI  - Closing the Gender Gap: Increased Female Authorship in AJR and Radiology.
AB  - OBJECTIVE: The purpose of this study was to evaluate gender differences in the
      authorship of original research articles by radiologists in two major American
      radiology journals, AJR and Radiology. MATERIALS AND METHODS: In a retrospective
      bibliometric analysis, all original articles published in AJR and Radiology
      during three 3-year periods (1991-1993, 2001-2003, and 2011-2013) were reviewed
      to determine the gender of the first and corresponding radiology authors. In
      addition, radiologic subspecialty and country of the authors were also abstracted
      from each article. RESULTS: The gender of the first and corresponding authors
      could be determined for 10,043 of 10,228 authors (98.2%) of original research in
      radiology. Between the periods 1991-1993 and 2011-2013, the percentage of female
      authors significantly increased: from 20.4% to 34.4%, respectively, among first
      authors (p < 0.0001); and from 18.0% to 28.7%, respectively, among corresponding
      authors (p < 0.0001). There was a significant correlation between the gender of
      the first and corresponding authors (p < 0.05). In the 2011-2013 period, the
      proportion of female authors was highest in breast (64.2%) and pediatric (48.2%)
      and lowest in vascular and interventional (18.5%) and cardiac (21.0%)
      subspecialties. The proportion of female authors was the highest in The
      Netherlands (47.3%), South Korea (37.9%), France (36.2%), and Italy (33.6%).
      CONCLUSION: There was a significant increase in the female authorship of original
      research articles in two major American radiology journals between the periods
      1991-1993 and 2011-2013.

PMID- 26204271
TI  - Apparent Diffusion Coefficient of Normal Abdominal Organs and Bone Marrow From
      Whole-Body DWI at 1.5 T: The Effect of Sex and Age.
AB  - OBJECTIVE: The objectives of this study were to define the range of apparent
      diffusion coefficients (ADCs) from whole-body DWI in normal abdominal organs and
      bone marrow, to identify ADC differences between sexes and changes occurring with
      age, and to evaluate the effect of the fat fraction (FF) on the ADC of normal
      liver parenchyma and bone marrow. MATERIALS AND METHODS: Fifty-one healthy
      volunteers (mean age = 38 years; age range = 23-68 years) underwent whole-body
      DWI using single-shot echo-planar imaging (b = 0, 150, 400, 750, and 1000
      s/mm(2)). A two-point Dixon technique was used to evaluate the FF. Perfusion
      sensitive ADCs, which we refer to as "ADCALL," and perfusion-insensitive ADCs,
      which we refer to as "ADCHIGH," of the liver and renal parenchyma, spleen,
      pancreatic tail, and red and yellow bone marrow were calculated. The
      relationships between ADC and sex, age, and FF were examined. RESULTS: ADCALL and
      ADCHIGH were significantly higher in female volunteers for the pancreatic tail (p
      = 0.046 and 0.008, respectively), red bone marrow (p = 0.029 and 0.001), and
      yellow bone marrow (p < 0.001 for both) but with considerable overlap. There were
      significant negative correlations between ADCALL and ADCHIGH and age in the liver
      parenchyma (p = 0.008 and 0.01, respectively) and in the yellow bone marrow (p =
      0.013 and 0.039) for all subjects. ADCALL and ADCHIGH were also negatively
      correlated with FF in the liver parenchyma (p = 0.006 and 0.008, respectively)
      and in yellow bone marrow (p < 0.001 and p = 0.001) in all subjects. CONCLUSION:
      The ADCs of normal liver parenchyma and bone marrow change significantly with
      age. The ADCs of bone marrow in women are significantly higher than those of men
      and correlate strongly with FF. These effects may have an impact on image
      interpretation when using whole-body DWI to assess disease burden and treatment
      response.

PMID- 26204272
TI  - All You Need to Know as an Authorized User.
AB  - OBJECTIVE: The purpose of this article is to review the training requirements for
      practicing nuclear radiology, the scope of licensing, how to start a new
      practice, and the key concepts an authorized user needs to know for responsible
      use of radiopharmaceuticals. CONCLUSION: Physicians responsible for the daily
      operations of nuclear medicine clinics often find the regulations concerning the
      safe handling and administration of radiopharmaceuticals daunting. Even
      experienced authorized users have concerns about handling many new therapeutic
      agents. Those studying for certifying and subspecialty examinations or for
      maintenance of certification for the American Board of Nuclear Medicine and the
      American Board of Radiology must clearly understand the overall process for
      becoming an authorized user.

PMID- 26204273
TI  - (18)F-FDG PET/CT and Melanoma: Staging, Immune Modulation and Mutation-Targeted
      Therapy Assessment, and Prognosis.
AB  - OBJECTIVE: Monoclonal antibodies that target the programmed cell death 1 (PD-1)
      immune checkpoint protein and its associated ligands, PD-L1 and PD-L2, and
      targeted inhibitors of mutated signal transduction molecules such as BRAF
      inhibitors show immense promise in treating patients with melanoma. We discuss
      the use of (18)F-FDG PET/CT for assessing therapy effectiveness, staging advanced
      disease, and determining prognosis of patients with melanoma. CONCLUSION: FDG
      PET/CT is useful in staging disease, assessing therapy, and determining prognosis
      in patients with melanoma.

PMID- 26204274
TI  - Overdiagnosis of Pulmonary Embolism by Pulmonary CT Angiography.
AB  - OBJECTIVE: The purpose of this study is to evaluate the rate of overdiagnosis of
      pulmonary embolism (PE) by pulmonary CT angiography (CTA) in a tertiary-care
      university hospital. MATERIALS AND METHODS: This study is a retrospective review
      of all pulmonary CTA examinations performed in a tertiary-care university
      hospital over a 12-month period. Studies originally reported as positive for PE
      were retrospectively reinterpreted by three subspecialty chest radiologists with
      more than 10 years' experience. A pulmonary CTA was considered negative for PE
      when all three chest radiologists were in agreement that the pulmonary CTA study
      was negative for PE. The location and potential causes for PE overdiagnosis were
      recorded. RESULTS: A total of 937 pulmonary CTA studies were performed over the
      study period. PE was diagnosed in the initial report in 174 of these cases
      (18.6%). There was discordance between the chest radiologists and the original
      radiologist in 45 of 174 (25.9%) cases. Discordance occurred more often where the
      original reported PE was solitary (46.2% of reported solitary PEs were considered
      negative on retrospective review) and located in a segmental or subsegmental
      pulmonary artery (26.8% of segmental and 59.4% of subsegmental PE diagnoses were
      considered negative on retrospective review). The most common cause of diagnostic
      difficulty was breathing motion artifact, followed by beam-hardening artifact.
      CONCLUSION: In routine clinical practice, PEs diagnosed by pulmonary CTA are
      frequently overdiagnosed, when compared with the consensus opinion of a panel of
      expert chest radiologists. Improvements in the quality of pulmonary CTA
      examination and increased familiarity with potential diagnostic pitfalls in
      pulmonary CTA are recommended to minimize misdiagnosis of PE.

PMID- 26204275
TI  - The National Lung Screening Trial Premise of Null and Chest Radiography
      Equivalence Is Open to Question.
AB  - OBJECTIVE: Lung cancer screening guidelines are based on the National Lung
      Screening Trial (NLST) that used chest radiographic control subjects on the
      premise of the reported mortality equivalence in chest radiography versus
      unscreened persons in the NLST-eligible subgroup of the Prostate, Lung,
      Colorectal and Ovarian Cancer Screening Trial. The purpose of this article is to
      discuss concerns regarding the validity of the NLST premise of chest radiography
      and null screening equivalence. CONCLUSION: Anomalous findings combined with the
      failure of CT trials using unscreened control subjects to replicate the benefits
      of the NLST open to question the validity of this premise.

PMID- 26204276
TI  - Response to "The National Lung Screening Trial Premise of Null and Chest
      Radiography Equivalence Is Open to Question".

PMID- 26204277
TI  - CT Detection of Symptomatic and Asymptomatic Meckel Diverticulum.
AB  - OBJECTIVE: The objective of our study was to determine how often symptomatic
      Meckel diverticulum and asymptomatic Meckel diverticulum are detected on CT in
      patients with known Meckel diverticulum and to evaluate factors that influence
      detection. MATERIALS AND METHODS: A total of 85 CT examinations of 40 patients
      (eight pediatric patients and 32 adult patients; 29 male patients and 11 female
      patients; average age, 46.2 +/- 23.7 [SD] years) with a pathologic diagnosis of
      Meckel diverticulum were retrospectively evaluated. These patients included 26
      adult patients with incidentally found asymptomatic Meckel diverticulum and 14
      patients (eight pediatric and six adult patients) with symptomatic Meckel
      diverticulum. The CT technical factors and patients' morphologic factors were
      compared with the detection of Meckel diverticulum using mixed-effect logistic
      regression models. RESULTS: Meckel diverticulum was detected on at least one CT
      examination in eight of 14 (57.1%) symptomatic patients (two of four patients
      with bleeding, two of six patients with small-bowel obstruction, two of two
      patients with acute diverticulitis, one of one patient with incisional hernia,
      and one of one patient with inverted Meckel diverticulum) and in 13 of 23 (56.5%)
      total CT examinations. Asymptomatic Meckel diverticulum was detected on at least
      one CT examination in 11 of 26 (42.3%) patients and in 16 of 62 (25.8%) total CT
      examinations. The amount of peritoneal fat was related to the detection of Meckel
      diverticula (p = 0.02). Although not statistically significant, the subjective
      quality of axial CT (p = 0.05) tended to be related to detection, whereas the use
      of IV (p = 0.59) or positive oral (p = 0.41) contrast material was unrelated to
      detection. In the original CT reports, none of the asymptomatic cases of Meckel
      diverticulum was prospectively detected, whereas Meckel diverticulum was detected
      or mentioned as a possibility in 64% of the symptomatic cases. CONCLUSION: In
      patients with known Meckel diverticulum, CT can detect Meckel diverticulum in up
      to 47.5% of all patients. Meckel diverticulum is more commonly detected in
      symptomatic patients than in asymptomatic patients, and detection is related to
      the amount of peritoneal fat.

PMID- 26204278
TI  - Differentiation of Sporadic Versus Tuberous Sclerosis Complex-Associated
      Angiomyolipoma.
AB  - OBJECTIVE: We review the imaging of renal angiomyolipomas, including
      differentiation of tuberous sclerosis complex (TSC)-associated and sporadic renal
      angiomyolipomas and other solid renal tumors. We also focus on radiologic
      interventions and molecular targeting of the TSC genetic pathway. CONCLUSION:
      Imaging plays a central role in the diagnosis and management of renal
      angiomyolipomas. It provides essential information to make the best therapeutic
      decisions about the interventional and pharmacologic options to help prevent
      bleeding and preserve functional parenchyma.

PMID- 26204279
TI  - Quantitative Versus Qualitative Methods in Evaluation of T2 Signal Intensity to
      Improve Accuracy in Diagnosis of Pheochromocytoma.
AB  - OBJECTIVE: The purpose of this study was to assess T2 signal intensity (SI) of
      adrenal pheochromocytoma at 1.5 T using the rapid acquisitions with relaxation
      enhancement (RARE) sequence. We also sought to determine whether quantitative
      parameters can distinguish pheochromocytoma from other adrenal lesions with
      better accuracy than conventional qualitative methods. MATERIALS AND METHODS: MRI
      examinations of 74 patients (26 with pheochromocytoma, 25 with lipid-poor
      adenomas, 18 with malignant adrenal lesions, and five with adrenal cysts) were
      retrospectively reviewed. MRI sequences included single-shot fast spin-echo (n =
      38) and fast-recovery fast spin-echo (n = 36) acquisitions. T2 SI of lesions was
      qualitatively compared with CSF. Quantitative evaluation included applying ROI
      measurements and calculating SI ratio of each mass to liver, spleen, paraspinal
      muscle, and CSF. Twoway ANOVA compared SI ratios between different adrenal
      lesions and between two pulse sequences. ROC analysis determined the optimal
      threshold SI ratio for distinguishing pheochromocytomas from other adrenal
      lesions. RESULTS: Sixty-nine percent of pheochromocytomas displayed isointensity
      to CSF (p < 0.005), resulting in 81% specificity and 69% sensitivity for
      differentiation of pheochromocytomas from lipid-poor adenomas and malignant
      lesions. Adrenal-to-muscle SI ratio was the strongest discriminator for
      differentiation of pheochromocytomas from other lesions. A threshold of at least
      3.95 yielded 88% specificity and 81% sensitivity for distinguishing
      pheochromocytomas from lipid-poor adenomas and malignant adrenal lesions.
      CONCLUSION: Quantitative normalization of T2 SI with reference to muscle improves
      the sensitivity and specificity profile for differentiation of pheochromocytoma
      compared with qualitative assessment alone. At 1.5 T field strength, an adrenal
      to-muscle SI ratio of at least 3.95 is recommended.

PMID- 26204280
TI  - MRI Findings of Inverted Urothelial Papilloma of the Bladder.
AB  - OBJECTIVE: The objective of this study was to characterize MRI findings of
      inverted urothelial papilloma of the bladder. MATERIALS AND METHODS: Data
      pertaining to 16 patients with 18 pathologically proven inverted urothelial
      papillomas of the bladder who had undergone MRI were retrospectively collected
      from seven institutions. The shape and surface characteristics of the tumors were
      evaluated using T2-weighted MR images. In addition, the signal intensity of
      inverted urothelial papillomas was visually assessed on T1-weighted, T2-weighted,
      and DW images and on early and delayed phase contrast-enhanced images. RESULTS:
      The shape of the 18 inverted urothelial papillomas of the bladder was classified
      as polypoid with a stalk for 16 tumors (89%) and polypoid without a stalk for two
      tumors (11%). All stalks were surrounded by urine in the bladder. A total of 15
      of the tumor surfaces (83%) were nonpapillary and three (17%) were papillary. All
      12 of the inverted urothelial papillomas for which evaluable T1-weighted images
      were available were isointense with the bladder wall. The lesions had a slightly
      higher signal intensity than the bladder wall in 15 of the patients (83%) and
      showed isointensity with the bladder wall in three patients (17%). A total of
      three patients (17%) had tiny hyperintense foci noted on T2-weighted images. All
      16 of the inverted urothelial papillomas examined by DWI had very high signal
      intensity. All 13 of the lesions for which early phase images were obtained using
      dynamic contrast-enhanced MRI showed strong enhancement. When compared with early
      phase images, delayed phase images of the same 13 lesions showed that enhancement
      was stronger in two lesions (15%), similar in six lesions (46%), and weaker in
      five lesions (38%). CONCLUSION: On MRI, the typical appearance of inverted
      urothelial papillomas of the bladder is a polypoid shape with a nonpapillary
      surface and a thin short stalk surrounded by urine. Cystic foci are also
      occasionally seen within the tumor.

PMID- 26204281
TI  - DWI for Renal Mass Characterization: Systematic Review and Meta-Analysis of
      Diagnostic Test Performance.
AB  - OBJECTIVE: The objective of our study was to perform a systematic review and meta
      analysis of the test performance of DWI in the characterization of renal masses.
      MATERIALS AND METHODS: We performed searches of three electronic databases for
      studies on renal mass characterization using DWI. Methodologic quality was
      assessed for each study. We quantitatively analyzed test performance for three
      clinical problems: first, benign versus malignant lesions; second, clear cell
      renal cell carcinoma (RCC) versus other malignancies; and, third, high-versus low
      grade clear cell RCCs. We summarized performance as a single pair of sensitivity
      and specificity values or a summary ROC curve. RESULTS: The studies in the
      literature were limited in both quantity and quality. For classification of
      benign versus malignant lesions, four studies with 279 lesions yielded a single
      summary estimate of 86% sensitivity and 78% specificity. For differentiation of
      clear cell RCC from other malignancies, five studies showed marked heterogeneity
      not conducive to meta-analysis. For differentiation of high-from low-grade clear
      cell RCCs, three studies with 110 lesions showed a threshold effect appropriate
      for summary ROC construction: The AUC was 0.83. CONCLUSION: Evidence suggests
      moderate accuracy of DWI for the prediction of malignancy and high-grade clear
      cell cancers, whereas DWI performance for ascertaining clear cell histologic
      grade remains unclear. To develop DWI as a noninvasive approach for the
      evaluation of solid renal masses, prospective studies with standardized test
      parameters are needed to better establish DWI performance and its impact on
      patient outcomes.

PMID- 26204282
TI  - Utility of MRI in the Characterization of Indeterminate Small Renal Lesions
      Previously Seen on Screening CT Scans of Potential Renal Donor Patients.
AB  - OBJECTIVE: The purpose of this study was to determine whether MRI could more
      confidently characterize indeterminate small renal lesions (< 15 mm) previously
      seen on CT scans of potential renal donor patients and whether such
      characterization could impact surgical management and donor candidate status.
      MATERIALS AND METHODS: After dedicated contrast-enhanced renal CT examinations of
      a population of renal donor patients identified indeterminate small renal lesions
      (< 15 mm), dedicated renal MRI examinations were performed for 55 of those
      patients. Two radiologists used consensus reading of established MRI
      characteristics to characterize indeterminate small lesions as simple cysts,
      hemorrhagic cysts, angiomyolipomas, or solid renal masses. RESULTS: A total of 94
      indeterminate small renal lesions were detected on CT. MRI was able to
      confidently diagnose 93 of those lesions, including 83 cysts, eight hemorrhagic
      cysts, and two angiomyolipomas. MRI directly affected the surgical management of
      four of the patients (7%). CONCLUSION: For potential renal donor patients, MRI
      can be an effective means of characterizing lesions that are deemed to be too
      small to characterize by CT. MRI can also potentially alter the surgical
      management and donor status of this group of patients.

PMID- 26204283
TI  - Apparent Diffusion Coefficient Values of the Benign Central Zone of the Prostate:
      Comparison With Low- and High-Grade Prostate Cancer.
AB  - OBJECTIVE: The apparent diffusion coefficient (ADC) values for benign central
      zone (CZ) of the prostate were compared with ADC values of benign peripheral zone
      (PZ), benign transition zone (TZ), and prostate cancer, using histopathologic
      findings from radical prostatectomy as the reference standard. MATERIALS AND
      METHODS: The study included 27 patients with prostate cancer (mean [+/- SD] age,
      60.0 +/- 7.6 years) who had 3-T endorectal coil MRI of the prostate performed
      before undergoing prostatectomy with whole-mount histopathologic assessment. Mean
      ADC values were recorded from the ROI within the index tumor and within benign
      CZ, PZ, and TZ, with the use of histopathologic findings as the reference
      standard. ADC values of the groups were compared using paired t tests and ROC
      curve analysis. RESULTS: The ADC of benign CZ in the right (1138 +/- 123 * 10(-6)
      mm(2)/s) and left (1166 +/- 141 * 10(-6) mm(2)/s) lobes was not significantly
      different (p = 0.217). However, the ADC of benign CZ (1154 +/- 129 * 10(-6)
      mm(2)/s) was significantly lower (p < 0.001) than the ADCs of benign PZ (1579 +/-
      197 * 10(-6) mm(2)/s) and benign TZ (1429 +/- 180 * 10(-6) mm(2)/s). Although the
      ADC of index tumors (1042 +/- 134 * 10(-6) mm(2)/s) was significantly lower (p =
      0.002) than the ADC of benign CZ there was no significant difference (p = 0.225)
      between benign CZ and tumors with a Gleason score of 6 (1119 +/- 87 * 10(-6)
      mm(2)/s). In 22.2% of patients (6/27), including five patients who had tumors
      with a Gleason score greater than 6, the ADC was lower in benign CZ than in the
      index tumor. The AUC of ADC for the differentiation of benign CZ from index
      tumors was 72.4% (sensitivity, 70.4%; specificity, 51.9%), and the AUC of ADC for
      differentiation from tumors with a Gleason score greater than 6 was 76.7%
      (sensitivity, 75.0%; specificity, 65.0%). CONCLUSION: The ADC of benign CZ is
      lower than the ADC of other zones of the prostate and overlaps with the ADC of
      prostate cancer tissue, including high-grade tumors. Awareness of this potential
      diagnostic pitfall is important to avoid misinterpreting the normal CZ as
      suspicious for tumor.

PMID- 26204284
TI  - JOURNAL CLUB: Evaluation of Near-Miss Wrong-Patient Events in Radiology Reports.
AB  - OBJECTIVE: The purpose of this study was to estimate the prevalence of reported
      near-miss wrong-patient events in radiology at two large academic hospitals and
      its relation to imaging modality, clinical setting, and time of occurrence.
      MATERIALS AND METHODS: An institutional imaging report database was searched for
      reports between January 1, 2009, and May 30, 2013, that contained the phrases
      "incorrect patient" or "wrong patient." These imaging reports were categorized
      into either mislabeled or misidentified patient or wrong dictation or report
      events. The mislabeling-misidentification events involved patients whose images
      were incorrectly placed in another patient's folder. In wrong dictation or report
      events, a patient's images were placed in the correct imaging folder, but another
      patient's images were used in error for dictation of the report. The time to
      detect each of these events was also evaluated. RESULTS: Overall, 67 eligible
      reports were identified among 1,717,713 examinations performed during the study
      period. The estimated event rate was 4 per 100,000 examinations (mislabeling
      misidentification, 52%; wrong dictation, 48%). The monthly mean of mislabeling
      misidentification events was 0.7 (SD, 0.9) and of wrong dictation events was 0.6
      (SD, 0.7). The median time for mislabeling-misidentification reports to be
      identified was 22 hours and for wrong dictation reports was 0 hours. Portable
      chest radiography was the modality involved in 69% (24/35) of reported
      mislabeling-misidentification and 44% (14/32) of wrong dictation events (p =
      0.08); 43% (15/35) of mislabeling-misidentification and 28% (9/32) of wrong
      dictation events occurred during off hours; 63% (22/35) of mislabeling
      misidentification and 56% (18/32) of wrong dictation events occurred in the
      inpatient setting. CONCLUSION: Despite use of the dual-identifier technique
      mandated by The Joint Commission, the number of near-miss mislabeled patient
      events for imaging tests and the delay in awareness of these events were
      substantial, especially for radiography.

PMID- 26204285
TI  - Understanding Cost-Effectiveness Analyses: An Explanation Using Three Different
      Analyses of Lung Cancer Screening.
AB  - OBJECTIVE: Cost-effectiveness analyses (CEAs) contribute to informed decision
      making, at both the practitioner and societal levels; therefore, understanding
      CEAs is valuable for radiologists. In light of the recently published National
      Lung Cancer Screening Trial (NLST) CEA, we aim to explain the terminology,
      methods, and heterogeneity of CEAs. CONCLUSION: We compared the NLST results to
      two example lung cancer screening CEAs (which do not rely on NLST data). Both
      examples assessed screening but reached substantially different conclusions.

PMID- 26204286
TI  - Treatment Response Assessment for Bladder Cancer on CT Based on Computerized
      Volume Analysis, World Health Organization Criteria, and RECIST.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of our
      autoinitialized cascaded level set 3D segmentation system as compared with the
      World Health Organization (WHO) criteria and the Response Evaluation Criteria In
      Solid Tumors (RECIST) for estimation of treatment response of bladder cancer in
      CT urography. MATERIALS AND METHODS: CT urograms before and after neoadjuvant
      chemo-therapy treatment were collected from 18 patients with muscle-invasive
      localized or locally advanced bladder cancers. The disease stage as determined on
      pathologic samples at cystectomy after chemotherapy was considered as reference
      standard of treatment response. Two radiologists measured the longest diameter
      and its perpendicular on the pre- and posttreatment scans. Full 3D contours for
      all tumors were manually outlined by one radiologist. The autoinitialized
      cascaded level set method was used to automatically extract 3D tumor boundary.
      The prediction accuracy of pT0 disease (complete response) at cystectomy was
      estimated by the manual, autoinitialized cascaded level set, WHO, and RECIST
      methods on the basis of the AUC. RESULTS: The AUC for prediction of pT0 disease
      at cystectomy was 0.78 +/- 0.11 for autoinitialized cascaded level set compared
      with 0.82 +/- 0.10 for manual segmentation. The difference did not reach
      statistical significance (p = 0.67). The AUCs using RECIST criteria were 0.62 +/-
      0.16 and 0.71 +/- 0.12 for the two radiologists, both lower than those of the two
      3D methods. The AUCs using WHO criteria were 0.56 +/- 0.15 and 0.60 +/- 0.13 and
      thus were lower than all other methods. CONCLUSION: The pre- and posttreatment 3D
      volume change estimates obtained by the radiologist's manual outlines and the
      autoinitialized cascaded level set segmentation were more accurate for
      irregularly shaped tumors than were those based on RECIST and WHO criteria.

PMID- 26204287
TI  - Osteoid Osteoma of the Femoral Neck: Use of the Half-Moon Sign in MRI Diagnosis.
AB  - OBJECTIVE: Osteoid osteoma is a benign bone tumor that is commonly located in the
      proximal femur. Although CT is helpful in the diagnosis of osteoid osteoma,
      patients in whom the clinical presentation of the tumor is atypical are first
      referred to undergo MRI, which yields a high percentage of false-negative or
      inconclusive results. We sought to explore the association between a half-moon
      sign of bone marrow edema and the presence of osteoid osteoma of the femoral
      neck. SUBJECTS AND METHODS: The MRI examinations of 11 consecutive patients with
      osteoid osteoma (group 1) were prospectively included in the study. In addition,
      950 consecutive hip MRI examinations of 485 patients were retrospectively
      analyzed for the presence of bone marrow edema of the femoral neck, with 19
      patients identified as having bone marrow edema resulting from causes other than
      osteoid osteoma (group 2). Patients in both study groups were evaluated for the
      presence of the half-moon sign. RESULTS: The half-moon sign of bone marrow edema
      was significantly associated with the presence of osteoid osteoma (p < 0.0001),
      having been seen on the MR images of all 11 patients in group 1 and only one of
      19 patients in group 2. MRI examination was therefore 94.7% specific and 100%
      sensitive for the detection of osteoid osteoma, with positive and negative
      predictive values of 91.7% and 100%, respectively. CONCLUSION: The half-moon sign
      is an MRI finding that is highly specific and sensitive for an accurate diagnosis
      of osteoid osteoma of the femoral neck.

PMID- 26204288
TI  - The Notch of Harty (Pseudodefect of the Tibial Plafond): Frequency and
      Characteristic Findings at MRI of the Ankle.
AB  - OBJECTIVE: The purpose of this study is to report the frequency and
      characteristic findings of the notch of Harty as seen on MRI. MATERIALS AND
      METHODS: One hundred six consecutive ankle MRI studies performed at 1.5 or 3 T
      were reviewed retrospectively by two radiologists. Findings relating to the notch
      of Harty and ankle joint were recorded and analyzed, including qualitative
      assessment of the presence of the notch, focal chondral thinning or focal
      subcortical osteosclerosis at the notch, notch width and depth, osteochondral
      lesions elsewhere in the ankle, subchondral edema signal or cystic change at the
      tibial plafond, and the presence of an ankle joint effusion. RESULTS: The study
      group of 106 patients consisted of 48 male and 58 female patients, with a mean
      age of 44.5 years (SD, 17.5 years). The notch was identified in 48 of 106
      patients (45%) (24 male and 24 female patients; mean age, 43.1 years; range, 7-79
      years). When present, the notch averaged 6.2 mm (SD, 1.6 mm) in width and 1.2 mm
      (SD, 0.5 mm) in depth. The notch was graded as prominent in six of the 106 ankle
      MRI examinations (6%). Subchondral edemalike signal or cystic change was not
      localized to the notch in any case. Between patients with versus those without a
      notch, there was no statistically significant difference in age, sex, subjacent
      subcortical osteosclerosis, ankle joint effusion, osteochondral lesions elsewhere
      in the ankle, or subchondral bone marrow edema at the tibial plafond. CONCLUSION:
      The notch of Harty can be observed as an anatomic variant on MRI and should be
      differentiated from a traumatic osteochondral lesion.

PMID- 26204289
TI  - Use of Tomosynthesis for Detection of Bone Erosions of the Foot in Patients With
      Established Rheumatoid Arthritis: Comparison With Radiography and CT.
AB  - OBJECTIVE: The purpose of this study was to compare tomosynthesis with
      radiography for the detection of bone erosions of the foot in patients with
      established rheumatoid arthritis (RA) using MDCT as a reference standard.
      SUBJECTS AND METHODS: Eighteen consecutive patients with established RA were
      included. Each patient underwent radiography, tomosynthesis, and CT examinations
      of the feet on the same day. Two radiologists independently determined the number
      of bone erosions and the Sharp-van der Heijde score with each of the three
      imaging modalities. RESULTS: On a total of 216 joints from 18 patients, 216 bone
      erosions were detected on CT, 215 on tomosynthesis, and 181 with radiography. The
      mean (+/- SD) Sharp-van der Heijde score was equivalent for tomosynthesis (18.8
      +/- 16.8) and CT (19.8 +/- 18.5) but was statistically lower for radiography
      (16.4 +/- 18.0) (p = 0.030). The respective overall sensitivity, specificity,
      accuracy, positive predictive value, and negative predictive value for
      tomosynthesis were 80%, 75%, 78%, 76%, and 80%, whereas the respective
      corresponding values for radiography were 66%, 81%, 74%, 77%, and 71%. The
      radiation burden of tomosynthesis was almost equivalent to that of radiography.
      CONCLUSION: Tomosynthesis has a higher sensitivity than radiography to detect
      bone erosions of the foot in patients with established RA and imparts an almost
      equivalent radiation burden.

PMID- 26204290
TI  - Evaluation of the Articular Cartilage of the Knee Joint Using an Isotropic
      Resolution 3D Fast Spin-Echo Sequence With Conventional and Radial Reformatted
      Images.
AB  - OBJECTIVE: The purpose of this study was to determine whether the use of radial
      reformatted images could improve the diagnostic performance of a 3D fast spin
      echo (FSE) sequence for detecting surgically confirmed cartilage lesions within
      the knee joint. MATERIALS AND METHODS: An MRI examination consisting of five 2D
      FSE sequences and a sagittal 3D FSE sequence was performed at 3 T on the knee
      joint of 150 patients who underwent subsequent knee arthroscopy, which included
      grading of the articular cartilage. Conventional axial, sagittal, and coronal
      reformatted images and radial reformatted images were created from the 3D FSE
      source data. Two musculoskeletal radiologists independently used the 2D FSE
      sequences, the 3D FSE sequence with conventional reformatted images only, and the
      3D FSE sequence with both radial and conventional reformatted images at three
      separate sessions to grade each articular surface of the knee joint. McNemar
      tests were used to compare diagnostic performance for detecting cartilage lesions
      using arthroscopy as the reference standard. RESULTS: The 3D FSE sequence with
      radial and conventional reformatted images had higher sensitivity (p < 0.001) and
      similar specificity (p = 0.73) to the 2D FSE sequences for detecting cartilage
      lesions and higher sensitivity (p < 0.001) and specificity (p = 0.002) than the
      3D FSE sequence with conventional reformatted images for detecting cartilage
      lesions. The 3D FSE sequence with conventional reformatted images had similar
      sensitivity (p = 0.93) and lower specificity (p = 0.005) than did the 2D FSE
      sequences for detecting cartilage lesions. CONCLUSION: A 3D FSE sequence had
      improved diagnostic performance compared with 2D FSE sequences for detecting
      cartilage lesions within the knee joint but only when using both radial and
      conventional reformatted images for cartilage evaluation.

PMID- 26204291
TI  - Model-Based Iterative Reconstruction (MBIR) for the Reduction of Metal Artifacts
      on CT.
AB  - OBJECTIVE: The purpose of this article is to study the added value of model-based
      iterative reconstruction (MBIR) on metal artifact reduction on CT compared with
      standard filtered back projection (FBP). MATERIALS AND METHODS: Ex vivo imaging
      was performed on several metal implants. Datasets were reconstructed with
      standard FBP and MBIR algorithms. The sizes of the artifacts surrounding the
      metal implant were recorded and compared. In vivo imaging was performed on 62
      patients with metal implants. Each dataset was reconstructed with FBP and MBIR
      algorithms. Objective image quality was assessed by measuring the size of the
      artifact generated by the metal implant. Subjective image quality was graded on a
      3-point scale, taking into account the visibility of the bone-metal interface, as
      well as the visibility of the neighboring soft tissues. RESULTS: Ex vivo analysis
      yielded a reduction of 82% in the size of the artifact when using the MBIR
      algorithm, compared with the FBP algorithm. The mean (SD) size of the artifacts
      was 1.4 +/- 0.8 and 0.25 +/- 0.06 cm(2) with FBP and MBIR, respectively. In vivo,
      the mean size of the artifacts decreased from 7.3 +/- 1.5 cm(2) to 4.0 +/- 0.9
      cm(2) for FBP and MBIR, respectively (p = 0.012). The subjective image quality
      analysis showed an equal or better bone-metal interface of MBIR algorithm in 85%
      of cases. Visibility of the soft tissue surrounding the metal implant was
      determined to be equal or better in 97% of cases in which MBIR was used.
      CONCLUSION: This study shows that the MBIR algorithm allows a clear reduction of
      metal artifacts on CT images and, hence, a better analysis of the soft tissue
      surrounding the metal implant compared with FBP.

PMID- 26204292
TI  - Cerebral Peduncle Angle: An Objective Criterion for Assessing Progressive
      Supranuclear Palsy Richardson Syndrome.
AB  - OBJECTIVE: Several criteria for time-consuming volumetric measurements of
      progressive supranuclear palsy Richardson syndrome subtype (PSP-RS) have been
      proposed. These often require image reconstruction in different planes for proper
      assessment. The purpose of this study was to evaluate the cerebral peduncle angle
      as a simple and reproducible measure of midbrain atrophy in patients with PSP-RS.
      MATERIALS AND METHODS: The records of 15 patients with PSP-RS were
      retrospectively identified. The records of 31 age-matched healthy control
      subjects, 15 patients with multiple-system atrophy, and 22 patients with
      Parkinson disease were included for comparison. Two neuroradiologists
      individually assessed these studies for midbrain atrophy by evaluating the
      cerebral peduncle angle, that is, the angle between the two cerebral peduncles.
      RESULTS: The cerebral peduncle angle measurements were 62.1 degrees  (SD, 6.8
      degrees ) in PSP-RS patients, 51.2 degrees  (SD, 10.1 degrees ) in healthy
      control subjects, 55.7 degrees  (SD, 11.6 degrees ) in patients with multiple
      system atrophy, and 53.7 degrees  (SD, 8.5 degrees ) in patients with Parkinson
      disease. A statistically significant difference was found in the cerebral
      peduncle angle measurements (observer 1, p = 0.015; observer 2, p = 0.004)
      between the PSP-RS patients and the other subgroups. Bland-Altman analysis showed
      a bias of 0.6 degrees  (95% limits of agreement, 6.9 degrees , -5.8 degrees ),
      and intraobserver variability analysis showed a bias of 0.5 degrees  (4.1 degrees
      , -3 degrees ). CONCLUSION: The cerebral peduncle angle is a simple, easy-to
      calculate, and reproducible measure of midbrain atrophy. It is a useful criterion
      for differentiating patients with PSP-RS from healthy persons and from patients
      with multiple-system atrophy or Parkinson disease.

PMID- 26204293
TI  - Successful Dose Reduction Using Reduced Tube Voltage With Hybrid Iterative
      Reconstruction in Pediatric Abdominal CT.
AB  - OBJECTIVE: The purpose of this article is to assess radiation dose reduction,
      image quality, and diagnostic confidence using low tube voltage in combination
      with hybrid iterative reconstruction in contrast-enhanced pediatric abdominal CT.
      MATERIALS AND METHODS: CT examinations of 133 patients (median age, 10 years)
      were performed at sequentially reduced doses. The first group (group 1) was
      scanned using dimension-based protocols at 120 kV for all patient sizes. The
      optimized group (group 5) was scanned at 80 kV for less than 18 cm in the lateral
      dimension and 100 kV in the 19-30 cm lateral dimension. CT examinations
      reconstructed with filtered back projection (FBP) and four levels of hybrid
      iterative reconstruction were reviewed by four blinded readers for subjective
      image quality and diagnostic confidence. Objective noise, volume CT dose index
      (CTDIvol), and size-specific dose estimate (SSDE) were recorded. Data were
      analyzed using t tests, one and two-way ANOVA, and the intraclass correlation
      coefficient. RESULTS: Compared with group 1, the radiation dose was reduced for
      group 5 by 63% measured by SSDE (4.69 vs 10.00 mGy; p < 0.001). Subjective image
      noise was increased for FBP images (p < 0.001) but not was statistically
      significantly different for all levels of hybrid iterative reconstruction;
      artifacts were reduced and visibility of small structures was improved (both p <
      0.001). Diagnostic confidence was improved for solid organ injury and metastatic
      disease (both p < 0.001) and was not statistically significantly different for
      appendicitis (p = 0.306). CONCLUSION: Use of hybrid iterative reconstruction with
      low-tube-voltage protocols enables substantial radiation dose reduction for
      pediatric abdominal CT with equivalent to improved subjective image quality and
      diagnostic confidence.

PMID- 26204294
TI  - Diagnostic Performance of Whole-Body MRI as a Tool for Cancer Screening in
      Children With Genetic Cancer-Predisposing Conditions.
AB  - OBJECTIVE: Children with cancer-predisposing conditions are at increased risk to
      develop and die of cancer. Limited data exist on the utility of whole-body MRI as
      a cancer screening tool in children. In this study, we examined the diagnostic
      performance of whole-body MRI as a mechanism of tumor surveillance for children
      at increased genetic risk for cancer. MATERIALS AND METHODS: Twenty-four children
      (six boys and 18 girls) with a mean age of 11.2 years (range, 2.1-18.2 years)
      underwent 50 unenhanced whole-body MRI examinations over a 5-year period. Scans
      were retrospectively reviewed and assessed for image quality; sequences
      performed; and the presence of osseous, soft-tissue, or solid organ
      abnormalities. Findings suggestive of a malignancy were stratified by risk as low
      (< 20% chance for cancer), moderate (20-80%), or high (> 80%). MRI findings were
      correlated with medical records, biopsy results, or additional follow-up imaging;
      biopsy and follow-up were considered as the reference standards. RESULTS: Forty
      eight of 50 (96%) examinations were of very good quality. Nine findings
      suspicious for malignancy were identified, including two high-risk, two moderate
      risk, and five low-risk lesions. One high-risk lesion was proven by biopsy to be
      a papillary thyroid carcinoma, with the remaining lesions deemed nonmalignant.
      The sensitivity of whole-body MRI was 100%; specificity, 94%; positive predictive
      value, 25%; and negative predictive value (NPV), 100%. CONCLUSION: Unenhanced
      whole-body MRI is safe and produces excellent images. The high sensitivity,
      specificity, and NPV make whole-body MRI a valuable cancer screening tool in
      children with a genetic predisposition for cancer.

PMID- 26204296
TI  - Management of Anticoagulant and Antiplatelet Medications in Adults Undergoing
      Percutaneous Interventions.
AB  - OBJECTIVE: Many radiologists are unfamiliar with the new antithrombogenic
      medications and how to modify patient management before nonvascular percutaneous
      procedures performed in a radiology department. In this article, we review the
      indications for use, mechanism of action, pharmacokinetics, dosing, and
      recommendations for periprocedural management of patients using these
      medications. CONCLUSION: To improve patient safety, radiologists involved in
      percutaneous procedures should have knowledge of the antithrombotics that will be
      encountered routinely in clinical practice.

PMID- 26204295
TI  - MRI and CT of Low-Grade Fibromyxoid Sarcoma in Children: A Report From Children's
      Oncology Group Study ARST0332.
AB  - OBJECTIVE: The purpose of this article is to determine the MRI and CT features of
      low-grade fibromyxoid sarcoma in children. MATERIALS AND METHODS: We
      retrospectively analyzed images of 11 pediatric patients with low-grade
      fibromyxoid sarcoma from a phase 3 clinical trial of nonrhabdomyosarcoma soft
      tissue sarcoma (Children's Oncology Group Protocol ARST0332). MRI and CT were
      performed in 10 and four patients, respectively. Location, size, margin, and
      composition on imaging were correlated with pathologic findings. RESULTS: Tumors
      were located in the extremities in nine patients, and one tumor each was located
      in the tongue and lung. Tumors were deep in seven patients and superficial in
      four patients. All tumors were well defined, solitary, and nonmetastatic at
      presentation. Tumors were complex solid-cystic in eight patients and completely
      solid in three patients. On T1-weighted images, all tumors had at least some
      areas hypointense to muscles, and six had a split-fat sign. On STIR or T2
      weighted images, eight tumors had areas hypointense to adjacent muscle, and eight
      tumors had fluid signal intensity. On contrast-enhanced MRI studies, eight tumors
      had thick enhancing internal septations, and three had peripheral nodular
      gyriform enhancement. When we correlated imaging to pathologic findings, areas
      with hypointense signal intensity on both T1- and T2-weighted images were likely
      related to fibrous component; areas with fluid signal intensity on T2-weighted
      images were likely related to myxoid component. On CT, all four tumors were
      hypodense to muscle, and one tumor showed punctate calcific foci. CONCLUSION: Low
      grade fibromyxoid sarcoma is hypodense to muscle on CT. MRI may identify both
      fibrous and myxoid components of this rare pediatric soft-tissue sarcoma.

PMID- 26204297
TI  - Use of Imaging in the Management of Metastatic Spine Disease With Percutaneous
      Ablation and Vertebral Augmentation.
AB  - OBJECTIVE: The purpose of this article is to describe the role of imaging in the
      management of metastatic spine disease with percutaneous ablation and vertebral
      augmentation. Topics include the imaging diagnosis of spinal metastases, imaging
      factors related to patient selection and procedural planning, intraprocedural
      imaging guidance, and posttreatment imaging assessment. CONCLUSION: Radiologists
      should be familiar with pertinent imaging findings related to the percutaneous
      management of metastatic spine disease.

PMID- 26204298
TI  - Frequency of Malignancy and Imaging Characteristics of Probably Benign Lesions
      Seen at Breast MRI.
AB  - OBJECTIVE: The purposes of this study were to evaluate the frequency, follow-up
      compliance, and cancer rate of MRI BI-RADS category 3 lesions and to determine
      the cancer rate for individual BI-RADS descriptors. MATERIALS AND METHODS: A
      retrospective review was conducted of breast MRI examinations with an assessment
      of probably benign (BI-RADS category 3) from among 4279 consecutive breast MRI
      examinations performed from January 2005 through December 2009. The review
      revealed 282 (6.6%) examinations with 332 lesions defined as BI-RADS 3.
      Pathologic results, 2 years of follow-up imaging findings, or both were reviewed.
      The frequency of BI-RADS 3 assessments, follow-up imaging compliance, and cancer
      yield were calculated. Three fellowship-trained breast imagers reevaluated all
      lesions and recorded descriptors from the MRI lexicon of the fifth edition of the
      BI-RADS atlas. The distribution and likelihood of malignancy for each descriptor
      were calculated. RESULTS: The follow-up compliance rate was 84.3% (280/332), and
      the malignancy rate was 4.3% (12/280). There were 50 (17.9%) individual foci, 61
      (21.8%) multiple foci, 74 (26.4%) masses, and 95 (33.9%) nonmass enhancement
      lesions. Masses were most commonly oval (59.5% [44/74]), circumscribed (75.7%
      [56/74]), and homogeneously enhancing (43.2% [32/74]). Nonmass enhancement was
      most commonly focal (57.9% [55/95]) with heterogeneous enhancement (53.7%
      [51/95]) Most of the lesions had persistent kinetics (74.3% [208/280]). The
      background parenchymal enhancement was most commonly mild (51.1% [143/280]).
      CONCLUSION: MRI BI-RADS category 3 is not frequently used, and the levels of
      patient compliance with follow-up imaging are acceptable. The cancer yield for
      probably benign lesions is greater for MRI-detected than for mammographically
      detected lesions, especially for specific BI-RADS descriptors.

PMID- 26204299
TI  - Quantitative Maximum Shear-Wave Stiffness of Breast Masses as a Predictor of
      Histopathologic Severity.
AB  - OBJECTIVE: The objective of our study was to compare quantitative maximum breast
      mass stiffness on shear-wave elastography (SWE) with histopathologic outcome.
      SUBJECTS AND METHODS: From September 2008 through September 2010, at 16 centers
      in the United States and Europe, 1647 women with a sonographically visible breast
      mass consented to undergo quantitative SWE in this prospective protocol; 1562
      masses in 1562 women had an acceptable reference standard. The quantitative
      maximum stiffness (termed "Emax") on three acquisitions was recorded for each
      mass with the range set from 0 (very soft) to 180 kPa (very stiff). The median
      Emax and interquartile ranges (IQRs) were determined as a function of
      histopathologic diagnosis and were compared using the Mann-Whitney U test. We
      considered the impact of mass size on maximum stiffness by performing the same
      comparisons for masses 9 mm or smaller and those larger than 9 mm in diameter.
      RESULTS: The median patient age was 50 years (mean, 51.8 years; SD, 14.5 years;
      range, 21-94 years), and the median lesion diameter was 12 mm (mean, 14 mm; SD,
      7.9 mm; range, 1-53 mm). The median Emax of the 1562 masses (32.1% malignant) was
      71 kPa (mean, 90 kPa; SD, 65 kPa; IQR, 31-170 kPa). Of 502 malignancies, 23
      (4.6%) ductal carcinoma in situ (DCIS) masses had a median Emax of 126 kPa (IQR,
      71-180 kPa) and were less stiff than 468 invasive carcinomas (median Emax, 180
      kPa [IQR, 138-180 kPa]; p = 0.002). Benign lesions were much softer than
      malignancies (median Emax, 43 kPa [IQR, 24-83 kPa] vs 180 kPa [IQR, 129-180 kPa];
      p < 0.0001). Usual benign lesions were soft, including 62 cases of fibrocystic
      change (median Emax, 32 kPa; IQR, 24-94 kPa), 51 cases of fibrosis (median Emax,
      36 kPa; IQR, 22-102 kPa), and 301 fibroadenomas (median Emax, 45 kPa; IQR, 30-79
      kPa). Eight lipomas (median Emax, 14 kPa; IQR, 8-15 kPa), 154 cysts (median Emax,
      29 kPa; IQR, 10-58 kPa), and seven lymph nodes (median Emax, 17 kPa; IQR, 9-40
      kPa) were softer than usual benign lesions (p < 0.0001 for lipomas and cysts; p =
      0.007 for lymph nodes). Risk lesions were slightly stiffer than usual benign
      lesions (p = 0.002) but tended to be softer than DCIS (p = 0.14). Fat necrosis
      and abscesses were relatively stiff. Conclusions were similar for both small and
      large masses. CONCLUSION: Despite overlap in Emax values, maximum stiffness
      measured by SWE is a highly effective predictor of the histopathologic severity
      of sonographically depicted breast masses.

PMID- 26204301
TI  - Ward.

PMID- 26204300
TI  - Patient and Radiologist Characteristics Associated With Accuracy of Two Types of
      Diagnostic Mammograms.
AB  - OBJECTIVE: Earlier studies of diagnostic mammography found wide unexplained
      variability in accuracy among radiologists. We assessed patient and radiologist
      characteristics associated with the interpretive performance of two types of
      diagnostic mammography. MATERIALS AND METHODS: Radiologists interpreting
      mammograms in seven regions of the United States were invited to participate in a
      survey that collected information on their demographics, practice setting, breast
      imaging experience, and self-reported interpretive volume. Survey data from 244
      radiologists were linked to data on 274,401 diagnostic mammograms performed for
      additional evaluation of a recent abnormal screening mammogram or to evaluate a
      breast problem, between 1998 and 2008. These data were also linked to patients'
      risk factors and follow-up data on breast cancer. We measured interpretive
      performance by false-positive rate, sensitivity, and AUC. Using logistic
      regression, we evaluated patient and radiologist characteristics associated with
      false-positive rate and sensitivity for each diagnostic mammogram type. RESULTS:
      Mammograms performed for additional evaluation of a recent mammogram had an
      overall false-positive rate of 11.9%, sensitivity of 90.2%, and AUC of 0.894;
      examinations done to evaluate a breast problem had an overall false-positive rate
      of 7.6%, sensitivity of 83.9%, and AUC of 0.871. Multiple patient characteristics
      were associated with measures of interpretive performance, and radiologist
      academic affiliation was associated with higher sensitivity for both indications
      for diagnostic mammograms. CONCLUSION: These results indicate the potential for
      improved radiologist training, using evaluation of their own performance relative
      to best practices, and for improved clinical outcomes with health care system
      changes to maximize access to diagnostic mammography interpretation in academic
      settings.

PMID- 26204302
TI  - What MRI Sequences Produce the Highest Specific Absorption Rate (SAR), and Is
      There Something We Should Be Doing to Reduce the SAR During Standard
      Examinations?

PMID- 26204303
TI  - Levoatriocardinal Vein and Mimics: Spectrum of Imaging Findings.
AB  - OBJECTIVE: This article focuses on the embryology, hemodynamics, and CT and MRI
      features of levoatriocardinal vein. Levoatriocardinal vein, a form of pulmonary
      systemic connection, is most commonly seen in left heart obstructive lesions,
      providing an alternative egress for pulmonary venous blood. CONCLUSION:
      Levoatriocardinal vein can be differentiated from other more common anomalies,
      such as anomalous pulmonary venous return, persistent left superior vena cava,
      and dilated left superior intercostal vein, by its distinctive imaging features.

PMID- 26204304
TI  - Radiation Dose Reduction in Dual-Energy CT: Does It Affect the Accuracy of
      Urinary Stone Characterization?
AB  - OBJECTIVE: The purpose of this article is to assess the effect of radiation dose
      reduction in dual-energy CT (DECT) on the performance of renal stone
      characterization using a patient cohort. MATERIALS AND METHODS: CT data from 39
      unenhanced DECT examinations performed for stone characterization were
      retrospectively analyzed in this study. Reduced-dose images were simulated at
      75%, 50%, and 25% of the routine dose using a previously validated noise
      insertion algorithm. Differentiation between uric acid (UA) and non-UA stones was
      performed using a fixed cutoff value for the dual-energy ratio. ROC analysis was
      performed to determine optimal cutoff values and the associated sensitivity and
      specificity. RESULTS: Of the 206 stones found, 43 were UA and 163 were non-UA.
      The mean (+/- SD) volume CT dose index (CTDIvol) was 16.0 +/- 4.0 mGy at the 100%
      dose level. The mean noise in 100-kV images increased from 40.9 +/- 6.8 HU at
      100% dose to 46.8 +/- 8.8 HU, 57.7 +/- 12.5 HU, and 85.4 +/- 22.9 HU at 75%, 50%,
      and 25% dose levels, respectively. Using the default cutoff value, for stones 10
      mm(3) or larger, the sensitivity/specificity were 100.0%/98.8%, 82.8%/98.8%, and
      89.3%/98.7%, at 75%, 50%, and 25% dose levels, respectively. ROC analysis showed
      varying optimal cutoff values at different dose levels. The sensitivity and
      specificity improved with use of these optimal cutoff values. Differentiation
      capability decreased for stones smaller than 10 mm(3). CONCLUSION: At 75% of the
      16-mGy routine dose, the sensitivity and specificity for differentiating UA from
      non-UA stones were minimally affected for stones 10 mm(3) or larger. The use of
      optimal cutoff values for dual-energy ratio as dose decreased (and noise
      increased) provided improved performance.

PMID- 26204305
TI  - Real-Time MRI-Guided Focused Ultrasound for Focal Therapy of Locally Confined Low
      Risk Prostate Cancer: Feasibility and Preliminary Outcomes.
AB  - OBJECTIVE: Focal therapy is an emerging approach to the treatment of localized
      prostate cancer. The purpose of this study was to report the 6-month follow-up
      oncologic and functional data of the initial phase 1 trial of patients treated
      with focal transrectal MRI-guided focused ultrasound in North America. SUBJECTS
      AND METHODS: Four patients with a prostate-specific antigen (PSA) level of 10
      ng/mL or less, tumor classification cT2a or less, and a Gleason score of 6 (3 +
      3) were prospectively enrolled in the study and underwent multiparametric MRI and
      transrectal ultrasound-guided prostate systematic biopsy. Under MRI guidance and
      real-time monitoring with MR thermography, focused high-frequency ultrasound
      energy was delivered to ablate the target tissue. The incidence and severity of
      treatment-related adverse events were recorded along with responses to serial
      quality-of-life questionnaires for 6 months after treatment. Oncologic outcomes
      were evaluated with multiparametric MRI and repeat transrectal ultrasound-guided
      biopsy 6 months after treatment. RESULTS: Four patients with a total of six
      target lesions were treated and had complications graded Clavien-Dindo I or less.
      Quality-of-life parameters were similar between baseline and 6-months. All four
      patients had normal MRI findings in the treated regions (100%), biopsy showed
      that three patients (75%) were clear of disease in the treated regions,
      representing complete ablation of five target lesions (83%). All patients had at
      least one Gleason 6-positive core outside of the treated zone. CONCLUSION: MRI
      guided focused ultrasound is a feasible method of noninvasively ablating low-risk
      prostate cancers with low morbidity. Further investigation and follow-up are
      warranted in a larger patient series with appropriate statistical analysis of
      oncologic and functional outcome measures.

PMID- 26204306
TI  - Anterior Prostate Cancer: Diagnostic Performance of T2-Weighted MRI and an
      Apparent Diffusion Coefficient Map.
AB  - OBJECTIVE: Diagnosis of anterior prostate cancer is challenging. The purpose of
      this study was to evaluate the diagnostic performance of T2-weighted imaging and
      an apparent diffusion coefficient (ADC) map in the detection of anterior prostate
      cancer and to compare that with the diagnostic performance in the detection of
      posterior prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the
      records of 87 patients who underwent 3-T MRI that included T2-weighted imaging
      and diffusion-weighted imaging before radical prostatectomy. The prostate gland
      was divided into anterior and posterior segments, and the radiologists
      interpreted two protocols (T2-weighted imaging alone vs T2-weighted imaging and
      an ADC map) and sorted the confidence levels for the presence of prostate cancer
      into five grades. ROC analysis was performed to evaluate the diagnostic
      performance of each protocol for the detection of anterior and posterior prostate
      cancers. We also assessed the relative fractions of sensitivity and specificity
      between anterior and posterior prostate cancers. Additionally, the ADCs of
      noncancerous anterior fibromuscular stroma were measured and compared with the
      ADCs of anterior prostate cancers. RESULTS: The AUCs with T2-weighted imaging
      alone and with T2-weighted imaging and an ADC map were 0.75 and 0.88 for anterior
      prostate cancer, respectively, and were 0.70 and 0.81 for posterior prostate
      cancer. The sensitivity for detecting anterior prostate cancer was 90% and was
      significantly higher than that for detecting posterior prostate cancer in the
      protocol using T2-weighted imaging and an ADC map (p = 0.003) when scores of 3-5
      were considered as positive for prostate cancer. The ADC was significantly lower
      in anterior prostate cancer (mean, 0.80 * 10(-3) mm(2)/s) than in noncancerous
      anterior fibromuscular stroma (1.13 * 10(-3) mm(2)/s) (p < 0.001). CONCLUSION:
      The protocol using T2-weighted imaging and an ADC map showed higher accuracy for
      the detection of anterior prostate cancer than for the detection of posterior
      prostate cancer.

PMID- 26204307
TI  - Comparison of Utility of Histogram Apparent Diffusion Coefficient and R2* for
      Differentiation of Low-Grade From High-Grade Clear Cell Renal Cell Carcinoma.
AB  - OBJECTIVE: The purpose of this study was to compare histogram analysis of
      apparent diffusion coefficient (ADC) and R2* for differentiating low-grade from
      high-grade clear cell renal cell carcinoma (RCC). MATERIALS AND METHODS: Forty
      six patients with pathologically confirmed clear cell RCC underwent preoperative
      BOLD and DWI MRI of the kidneys. ADCs based on the entire tumor volume were
      calculated with b value combinations of 0 and 800 s/mm(2). ROI-based R2* was
      calculated with eight TE combinations of 6.7-22.8 milliseconds. Histogram
      analysis of tumor ADCs and R2* values was performed to obtain mean; median;
      width; and fifth, 10th, 90th, and 95th percentiles and histogram inhomogeneity,
      kurtosis, and skewness for all lesions. RESULTS: Thirty-three low-grade and 13
      high-grade clear cell RCCs were found at pathologic examination. The TNM
      classification and tumor volume of clear cell RCC significantly correlated with
      histogram ADC and R2* (rho = -0.317 to 0.506; p < 0.05). High-grade clear cell
      RCC had significantly lower mean, median, and 10th percentile ADCs but higher
      inhomogeneity and median R2* than low-grade clear cell RCC (all p < 0.05).
      Compared with other histogram ADC and R2* indexes, 10th percentile ADC had the
      highest accuracy (91.3%) in discriminating low- from high-grade clear cell RCC.
      R2* in discriminating hemorrhage was achieved with a threshold of 68.95 Hz. At
      this threshold, high-grade clear cell RCC had a significantly higher prevalence
      of intratumor hemorrhage (high-grade, 76.9%; low-grade, 45.4%; p < 0.05) and
      larger hemorrhagic area than low-grade clear cell RCC (high-grade, 34.9% +/-
      31.6%; low-grade, 8.9 +/- 16.8%; p < 0.05). CONCLUSION: A close relation was
      found between MRI indexes and pathologic findings. Histogram analysis of ADC and
      R2* allows differentiation of low- from high-grade clear cell RCC with high
      accuracy.

PMID- 26204308
TI  - Novel Dosimeter Using a Nontoxic Phosphor for Real-Time Monitoring of Patient
      Radiation Dose in Interventional Radiology.
AB  - OBJECTIVE: To our knowledge, no feasible method exists for real-time measurement
      of the radiation dose given to the patient during interventional radiology (IR)
      procedures. Therefore, we produced a prototype of a real-time dosimeter for
      patients undergoing IR that uses a nontoxic phosphor. The basic characteristics
      of the real-time dosimeter prototype are comparable to those of the previously
      used skin dose monitor, with the exception that our prototype has the distinct
      advantage of including multichannel sensors. CONCLUSION: The novel real-time
      dosimeter system is expected to be useful for measuring patient exposure to the
      radiation dose during IR procedures.

PMID- 26204309
TI  - Quantitative Skeletal Muscle MRI: Part 1, Derived T2 Fat Map in Differentiation
      Between Boys With Duchenne Muscular Dystrophy and Healthy Boys.
AB  - OBJECTIVE: The purpose of this study was to validate derived T2 maps as an
      objective measure of muscular fat for discrimination between boys with Duchenne
      muscular dystrophy (DMD) and healthy boys. SUBJECTS AND METHODS: Forty-two boys
      with DMD (mean age, 9.9 years) and 31 healthy boys (mean age, 11.4 years) were
      included in the study. Age, body mass index, and clinical function scale grade
      were evaluated. T1-weighted MR images and T2 maps with and without fat
      suppression were obtained. Fatty infiltration was graded 0-4 on T1-weighted
      images, and derived T2 fat values (difference between mean T2 values from T2 maps
      with and without fat suppression) of the gluteus maximus and vastus lateralis
      muscles were calculated. Group comparisons were performed. The upper limit of the
      95% reference interval of T2 fat values from the control group was applied.
      RESULTS: There was no significant difference in age or body mass index between
      groups. All healthy boys and 19 boys (45.2%) with DMD had a normal clinical
      function scale grade. Grade 1 fatty infiltration was seen in 90.3% (gluteus
      maximus) and 71.0% (vastus lateralis) of healthy boys versus 33.3% (gluteus
      maximus) and 52.4% (vastus lateralis) of boys with DMD. T2 fat values of boys
      with DMD were significantly longer than in the control group (p < 0.001). Using a
      95% reference interval for healthy boys for the gluteus maximus (28.3
      milliseconds) allowed complete separation from boys with DMD (100% sensitivity,
      100% specificity), whereas the values for the vastus lateralis (7.28
      milliseconds) resulted in 83.3% sensitivity and 100% specificity. CONCLUSION:
      Measurement of muscular fat with T2 maps is accurate for differentiating boys
      with DMD from healthy boys.

PMID- 26204310
TI  - Quantitative Skeletal Muscle MRI: Part 2, MR Spectroscopy and T2 Relaxation Time
      Mapping-Comparison Between Boys With Duchenne Muscular Dystrophy and Healthy
      Boys.
AB  - OBJECTIVE: The purpose of this study is to validate the use of MR spectroscopy
      (MRS) in measuring muscular fat and to compare it with T2 maps in differentiating
      boys with Duchenne muscular dystrophy (DMD) from healthy boys. SUBJECTS AND
      METHODS: Forty-two boys with DMD and 31 healthy boys were evaluated with MRI with
      (1)H-MRS and T2 maps. Grading of muscle fat and edema on conventional images,
      calculation of fat fractions ([fat / fat] + water) on MRS, and calculation of T2
      fat values on T2 maps of the gluteus maximus and vastus lateralis muscles were
      performed. Group comparisons were made. The 95% reference interval (RI) of fat
      fraction for the control group was applied and compared with T2 map results.
      RESULTS: Minimal fat on T1-weighted images was seen in 90.3% (gluteus maximus)
      and 71.0% (vastus lateralis) of healthy boys, versus 33.3% (gluteus maximus) and
      52.4% (vastus lateralis) of boys with DMD. Muscle edema was seen in none of the
      healthy boys versus 52.4% (gluteus maximus) and 57.1% (vastus lateralis) of the
      boys with DMD. Fat fractions were higher in the DMD group (52.7%, gluteus
      maximus; 27.3%, vastus lateralis) than in the control group (12.8%, gluteus
      maximus; 13.7%, vastus lateralis) (p < 0.001). The 95% RI for gluteus maximus
      (38.7%) resulted in 61.9% sensitivity and 100% specificity for differentiating
      boys with DMD from healthy boys, whereas the value for vastus lateralis (17.8%)
      resulted in 76.2% sensitivity and 100% specificity; both had lower accuracy than
      did T2 maps (100% sensitivity and specificity). There was a positive correlation
      between T2 fat values and fat fractions (p < 0.0001). CONCLUSION: In
      differentiation of the two groups, T2 maps were more accurate than MRS. Fat
      fractions can underestimate the actual amount of fat because of coexisting muscle
      edema in DMD.

PMID- 26204311
TI  - Medicolegal-Malpractice and Ethical Issues in Radiology.

PMID- 26204312
TI  - Preoperative Evaluation of Pancreatic Adenocarcinoma.

PMID- 26204313
TI  - Reply to "Preoperative Evaluation of Pancreatic Adenocarcinoma".

PMID- 26204314
TI  - Fluoroscopic Evaluation of Oropharyngeal Dysphagia.

PMID- 26204315
TI  - Understanding of Health Information by Patients.

PMID- 26204316
TI  - Tubercular Sarcoidosis: An Intriguing Concoction of Tuberculosis and Sarcoidosis.

PMID- 26204317
TI  - Reply to "Tubercular Sarcoidosis: An Intriguing Concoction of Tuberculosis and
      Sarcoidosis".

PMID- 26204318
TI  - Resilience and symptom reporting following mild traumatic brain injury in
      military service members.
AB  - PRIMARY OBJECTIVE: The purpose of this study was to examine the relationship
      between resilience and symptom reporting following mild traumatic brain injury
      (mTBI). It was hypothesized that, as resilience increases, self-reported symptoms
      would decrease. RESEARCH DESIGN: Cross-sectional design. METHODS AND PROCEDURES:
      Participants were 142 US military service members who sustained a mTBI, divided
      into three resilience groups based on participants' responses on the Response to
      Stressful Experiences Scale: Moderate (n = 42); High (n = 51); and Very High (n =
      49). Participants completed the Neurobehavioral Symptom Inventory (NSI) and PTSD
      Checklist-Civilian Version (PCL-C) within 12 months following injury. MAIN
      OUTCOMES AND RESULTS: There were significant main effects for the NSI total
      score, cognitive cluster and affective cluster, as well as for the PCL-C total
      score, avoidance cluster and hyperarousal cluster. Pairwise comparisons revealed
      that there was a negative relationship between resilience and self-reported
      symptoms overall. Specifically, participants with higher resilience reported
      fewer post-concussion and PTSD-related symptoms than participants with lower
      levels of resilience. CONCLUSIONS: These findings underscore the important role
      that resilience plays in symptom expression in military service members with mTBI
      and suggest that research on targeted interventions to increase resilience in the
      acute phase following injury is indicated.

PMID- 26204319
TI  - The relationship between self-reported sleep disturbance and polysomnography in
      individuals with traumatic brain injury.
AB  - PRIMARY OBJECTIVE: To characterize sleep architecture and self-reported sleep
      quality, fatigue and daytime sleepiness in individuals with TBI. Possible
      relationships between sleep architecture and self-reported sleep quality, fatigue
      and daytime sleepiness were examined. METHODS: Forty-four community-dwelling
      adults with TBI completed the Pittsburgh Sleep Quality Index (PSQI),
      Multidimensional Assessment of Fatigue (MAF) and Epworth Sleepiness Scale (ESS).
      They underwent two nights of in-laboratory nocturnal polysomnography (NPSG).
      Pearson product-moment correlation coefficients and hierarchical linear
      regression was used to analyse the data. RESULTS: Based on the PSQI cut-off score
      of >= 10, 22 participants were characterized as poor sleepers. Twenty-seven
      participants met criteria for clinically significant fatigue as measured by the
      GFI of the MAF. Fourteen participants met criteria for excessive daytime
      sleepiness as measured by the ESS. Poor sleep quality was associated with poor
      sleep efficiency, short duration of stage 2 sleep and long duration of rapid eye
      movement sleep. There was little-to-no association between high levels of fatigue
      or daytime sleepiness with NPSG sleep parameters. CONCLUSIONS: A high proportion
      of the sample endorsed poor sleep quality, fatigue and daytime sleepiness. Those
      who reported poorer sleep quality evidenced a shorter proportion of time spent in
      stage 2 sleep. These findings suggest that disruptions in stage 2 sleep might
      underlie the symptoms of sleep disturbance experienced following TBI.

PMID- 26204321
TI  - Injury of the corticoreticular pathway in patients with mild traumatic brain
      injury: A diffusion tensor tractography study.
AB  - BACKGROUND: Little is known about injury of the corticoreticular pathway (CRP) in
      patients with mild traumatic brain injury (TBI). The current study attempted to
      investigate injury of the CRP in patients with mild TBI, using diffusion tensor
      tractography (DTT). METHODS: This study recruited 29 consecutive patients with
      proximal weakness following mild TBI and 25 control subjects. The CRP was
      reconstructed and the fractional anisotropy (FA) value, apparent diffusion
      coefficient (ADC) value and fibre volume of the CRP were measured. The patients
      were classified according to the configurational classification of the CRP
      injury: type A-the CRP showed narrowing, type B-the CRP showed partial tearing at
      subcortical white matter or brainstem and type C-the CRP showed discontinuation
      at the subcortical white matter or brainstem. RESULT: No significant differences
      in FA and ADC of the CRP were observed between the patient and control groups (p
      > 0.05). In contrast, the tract volume of the CRP was significantly lower in the
      patient group than in the control group (p < 0.05). According to the
      configurational classification of the CRP injury on DTT, the patients were
      classified as follows: among 58 hemispheres of 29 patients: type A-9 hemispheres
      (15.5%) of eight patients, type B-30 hemispheres (51.7%) of 22 patients and type
      C-13 hemispheres (22.4%) of 11 patients. CONCLUSION: This study demonstrated
      injury of the CRP in patients who showed proximal weakness following mild TBI,
      using DTT.

PMID- 26204320
TI  - Syria civil war: Outcomes of humanitarian neurosurgical care provided to Syrian
      wounded refugees in Israel.
AB  - BACKGROUND: As an expected consequence of the civil war in Syria, emergent
      neurosurgical care for battlefield trauma has been provided for severely head
      injured Syrians transferred to Northern Israel. METHODS: Sixty-six patients
      suffering from brain injury were brought to the border and then referred to the
      institution after initial resuscitation. Both the time and type of injury were
      recorded based on paramedic testimony, forensic material or on details provided
      by patients. A retrospective analysis of all medical charts and imaging material
      was performed. RESULTS: Most injuries were combat-related, either caused by blast
      (13.6%), shrapnel (24.2%), assault (28.8%) or gunshot wound (15.2%). Only a
      minority of patients (18.2%) suffered from injuries that were not directly caused
      by weapon. A total of 55 surgical procedures were performed in 46 out of 66
      patients, including craniotomies in 40 patients, burr hole alone for placement of
      intraparenchymal intracranial pressure (ICP) sensor in nine instances and
      ventricle peritoneal shunt in two patients. Decompressive craniectomy was used
      only for the treatment of gunshot wound and was performed in eight out of 10
      patients. The most common complication consisted in cerebrospinal fluid fistulas
      (16.7%). Post-operative infections occurred in seven patients (10.6%). Short-term
      outcomes were favourable in 60.7%, with a mortality rate of 4.5%. DISCUSSION: The
      present findings suggest that aggressive surgery and neuro-intensive care
      measures may lead to good functional results, even in the presence of seemingly
      devastating injuries in some selected patients.

PMID- 26204322
TI  - Mobile Videoconferencing Apps for Telemedicine.
AB  - INTRODUCTION: The quality and performance of several videoconferencing
      applications (apps) tested on iOS (Apple, Cupertino, CA) and Android (Google,
      Mountain View, CA) mobile platforms using Wi-Fi (802.11), third-generation (3G),
      and fourth-generation (4G) cellular networks are described. MATERIALS AND
      METHODS: The tests were done to determine how well apps perform compared with
      videoconferencing software installed on computers or with more traditional
      videoconferencing using dedicated hardware. The rationale for app assessment and
      the testing methodology are described. RESULTS: Findings are discussed in
      relation to operating system platform (iOS or Android) for which the apps were
      designed and the type of network (Wi-Fi, 3G, or 4G) used. The platform, network,
      and apps interact, and it is impossible to discuss videoconferencing experienced
      on mobile devices in relation to one of these factors without referencing the
      others. CONCLUSIONS: Apps for mobile devices can vary significantly from other
      videoconferencing software or hardware. App performance increased over the
      testing period due to improvements in network infrastructure and how apps manage
      bandwidth.

PMID- 26204323
TI  - A novel antibody-drug conjugate anti-CD19(Fab)-LDM in the treatment of B-cell non
      Hodgkin lymphoma xenografts with enhanced anticancer activity.
AB  - BACKGROUND: Rituximab is widely used in clinical setting for the treatment of B
      malignant lymphoma and has achieved remarkable success. However, in most
      patients, the disease ultimately relapses and become resistant to rituximab. To
      overcome the limitation, there is still a need to find novel strategy for
      improving therapeutic efficacy. OBJECTIVE: To construct genetically engineered
      antibody anti-CD19(Fab)-LDM, and verify the anticancer activity targeted toward B
      lymphoma. METHODS: The anticancer activity of anti-CD19(Fab)-LDM in vitro and in
      vivo was examined. In vitro, the binding activity and internalization of anti
      CD19(Fab)-LDP were measured. Using comet assay and apoptosis, the cytotoxicity of
      energized fusion proteins was observed. From in vivo experiments, targeting of
      therapeutic effect and anticancer efficacy bythe fusion protein was verified.
      RESULTS: Data showed that anti-CD19(Fab)-LDM does not only binding the cell
      surface but is also internalized into the cell. The energized fusion proteins
      anti-CD19(Fab)-LDM can induce DNA damage. Furthermore, significant in vivo
      therapeutic efficacy was observed. CONCLUSION: The present study demonstrated
      that the genetically engineered antibody anti-CD19(Fab)-LDM exhibited enhanced
      cytotoxicity compared to LDM alone. One of the most powerful advantages of anti
      CD19(Fab)-LDM, however, is that it can be internalized within the cells and carry
      out cytotoxic effects. Therefore, anti-CD19(Fab)-LDM may be as a useful targeted
      therapy for B-cell lymphoma.

PMID- 26204324
TI  - Inhibitory effect of epirubicin-loaded lipid microbubbles with conjugated anti
      ABCG2 antibody combined with therapeutic ultrasound on multiple myeloma cancer
      stem cells.
AB  - Ultrasound-targeted microbubble destruction (UTMD) technique is thought to
      improve the chemotherapeutic agent delivery from microbubbles (MBs) in tumor
      tissues and reduce the side effects in non-tumor tissues. Multiple myeloma (MM)
      is a bone marrow cancer and remains to be an incurable disease. In this study, we
      used the UTMD technique to investigate the inhibitory effect of our developed
      novel reagent on MM cancer stem cells (CD138(-)CD34(-)MM CSCs) that are MM cells
      with CD138(-)CD34(-) phenotypes, responsible for MM-initiating potential, drug
      resistance and eventual relapse. The preparatory steps of novel reagent was first
      epirubicin (EPI)-loaded in the lipid MBs that was consisted of 1,2-distearoyl-sn
      glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]-biotin,
      dipalmitoyl-phosphatidylglycerol and 25-NBD-cholesterol, then anti-ABCG2
      monoclonal antibody (mAb) was conjugated onto the MB surface to form EPI-MBs+mAb.
      CD138(-)CD34(-)MM CSCs were isolated from human MM RPMI 8226 cell line by the
      magnetic associated cell sorting method. The results showed that the attenuated
      proliferation, migration and invasion ability, and increased apoptosis were
      observed when MM CSCs were incubated with a various agents. EPI-MBs+mAb combined
      with therapeutic ultrasound significantly promoted the MM CSC apoptosis compared
      with EPI, EPI-MBs alone or EPI-MBs+mAb without ultrasound exposure. These results
      suggest that the developed EPI-MBs+mAb combined with therapeutic ultrasound
      remarkably induced MM CSC apoptosis in vitro. 

PMID- 26204326
TI  - Microemulsions mediated effective delivery of methotrexate hydrogel: more than a
      tour de force in psoriasis therapeutics.
AB  - Methotrexate (MTX), a well known drug for the treatment of cancer and rheumatoid
      arthritis, has gained prominence in the treatment of psoriasis over the period of
      years. However, the present mode of systemic administration through oral or
      parenteral route has always proposition, full of compromises. The toxicity of
      drug to the vital organs and physiological environment is the major concern.
      Also, its poor skin penetration is one major problem. Hence novel system based on
      lipid carriers has been considered here to overcome the barriers. Microemulsions
      (MEs) were prepared using pseudo-ternary phase diagram (PTPD) and they were
      characterized for various parameters such as size, shape (cryo-SEM), PDI, zeta
      potential, etc. The chosen MEs system (optimized) was then incorporated into
      secondary vehicles and characterized for rheological behavior, texture profile
      analysis, in vitro release, ex vivo permeation and drug distribution into
      different layers of skin. The developed formulations were further evaluated in ex
      vivo and in vivo such as cell line study, imiquimod-induced psoriatic model,
      allergic contact dermatitis, rat tail model (% orthokeratosis) and safety test
      (Draize test). The MEs based MTX gel has shown its potential in locating the drug
      at the desired domain of stratum corneum, epidermal and dermal layers of skin and
      reducing systemic absorption. Our results are suggestive of MEs potential as a
      novel carrier for topical delivery of MTX in topical therapeutic and safety
      approaches. In conclusion, developed MEs-based hydrogel has shown promising
      results in achieving effective delivery of MTX. 

PMID- 26204325
TI  - Simultaneous targeting of VEGF-receptors 2 and 3 with immunoliposomes enhances
      therapeutic efficacy.
AB  - BACKGROUND: Tumor progression depends on angiogenesis. Vascular endothelial
      growth factor (VEGF) receptors (VEGFRs) are the main signal transducers that
      stimulate endothelial cell migration and vessel sprouting. At present, only
      VEGFR2 is targeted in the clinical practice. PURPOSE: To develop new, anti
      angiogenic nanoparticles (immunoliposomes, ILs), that redirect cytotoxic
      compounds to tumor-associated vascular cells. METHODS: Pegylated liposomal
      doxorubicin (PLD) was targeted against VEGFR2- and VEGFR3-expressing cells by
      inserting anti-VEGFR2 and/or anti-VEGFR3 antibody fragments into the lipid
      bilayer membrane of PLD. These constructs were tested in vitro, and in vivo in
      the Rip1Tag2 mouse model of human cancer. RESULTS: The combination treatment with
      anti-VEGFR2-ILs-dox and anti-VEGFR3-ILs-dox was superior to targeting only VEGFR2
      cells and provides a highly efficient approach of depleting tumor-associated
      vasculature. This leads to tumor starvation and pronounced reduction of tumor
      burden. CONCLUSION: Nanoparticles against VEGFR2 and -3 expressing tumor
      associated endothelial cells represent a promising and novel anti-cancer
      strategy.

PMID- 26204327
TI  - The clinical profile of employees with mental health problems working in social
      firms in the UK.
AB  - BACKGROUND: UK social firms are under-researched but are a potentially important
      vocational option for people with mental health problems. AIMS: To describe the
      clinical profile, satisfaction levels and experiences of social firms employees
      with mental health problems. METHOD: Clinical, work and service use
      characteristics were collected from social firms' employees with mental health
      problems in England and Wales. Workplace experience and satisfaction were
      explored qualitatively. RESULTS: Predominantly, social firms' employees (N = 80)
      report that they have a diagnosis of depression (56%) and anxiety (41%). People
      with schizophrenia (20%) or bipolar disorder (5%) were a minority. Respondents
      had low symptom and disability levels, high quality of life and job satisfaction
      and experienced reductions in secondary mental health service use over time. High
      workplace satisfaction was related to flexibility, manager and colleague support
      and workplace accommodations. CONCLUSIONS: The clinical profile, quality of life
      and job satisfaction level of employees with mental health problems suggest
      social firms could be a useful addition to UK vocational services for some
      people. Current employees mainly have common mental disorders, and social firms
      will need to shift their focus if they are to form a substantial pathway for the
      vocational recovery of people currently using community mental health teams.

PMID- 26204328
TI  - Controllable synthesis of molybdenum tungsten disulfide alloy for vertically
      composition-controlled multilayer.
AB  - The effective synthesis of two-dimensional transition metal dichalcogenides alloy
      is essential for successful application in electronic and optical devices based
      on a tunable band gap. Here we show a synthesis process for Mo1-xWxS2 alloy using
      sulfurization of super-cycle atomic layer deposition Mo1-xWxOy. Various
      spectroscopic and microscopic results indicate that the synthesized Mo1-xWxS2
      alloys have complete mixing of Mo and W atoms and tunable band gap by
      systematically controlled composition and layer number. Based on this, we
      synthesize a vertically composition-controlled (VCC) Mo1-xWxS2 multilayer using
      five continuous super-cycles with different cycle ratios for each super-cycle.
      Angle-resolved X-ray photoemission spectroscopy, Raman and ultraviolet-visible
      spectrophotometer results reveal that a VCC Mo1-xWxS2 multilayer has different
      vertical composition and broadband light absorption with strong interlayer
      coupling within a VCC Mo1-xWxS2 multilayer. Further, we demonstrate that a VCC
      Mo1-xWxS2 multilayer photodetector generates three to four times greater
      photocurrent than MoS2- and WS2-based devices, owing to the broadband light
      absorption. 

PMID- 26204329
TI  - Melatonin administration modifies circadian motor activity under constant light
      depending on the lighting conditions during suckling.
AB  - Early lighting conditions have been described to produce long-term effects on
      circadian behavior, which may also influence the response to agents acting on the
      circadian system. It has been suggested that melatonin (MEL) may act on the
      circadian pacemaker and as a scavenger of reactive oxygen and nitrogen species.
      Here, we studied the oxidative and behavioral changes caused by prolonged
      exposure to constant light (LL) in groups of rats that differed in MEL
      administration and in lighting conditions during suckling. The rats were exposed
      to either a light-dark cycle (LD) or LL. At 40 days old, rats were treated for 2
      weeks with a daily subcutaneous injection of MEL (10 mg/kg body weight) or a
      vehicle at activity onset. Blood samples were taken before and after treatment,
      to determine catalase (CAT) activity and nitrite level in plasma. As expected, LL
      reared rats showed a more stable motor activity circadian rhythm than LD rats.
      MEL treatment produced more reactivity in LD- than in LL rats, and was also able
      to alter the phase of the rhythm in LD rats. There were no significant
      differences in nitrite levels or CAT activity between the groups, although both
      variables increased with time. Finally, we also tested depressive signs by means
      of sucrose consumption, and anhedonia was found in LD males treated with MEL. The
      results suggest that the lighting conditions in early infancy are important for
      the long-term functionality of the circadian system, including rhythm
      manifestation, responses to MEL and mood alterations.

PMID- 26204330
TI  - Lymphatic Vascular Regeneration: The Next Step in Tissue Engineering.
AB  - The lymphatic system plays a crucial role in interstitial fluid drainage, lipid
      absorption, and immunological defense. Lymphatic dysfunction results in
      lymphedema, fluid accumulation, and swelling of soft tissues, as well as a
      potentially impaired immune response. Lymphedema significantly reduces quality of
      life of patients on a physical, mental, social, and economic basis. Current
      therapeutic approaches in treatment of lymphatic disease are limited. Over the
      last decades, great progress has been made in the development of therapeutic
      strategies to enhance vascular regeneration. These solutions to treat vascular
      disease may also be applicable in the treatment of lymphatic diseases. Comparison
      of the organogenic process and biological organization of the vascular and
      lymphatic systems and studies in the regulatory mechanisms involved in
      lymphangiogenesis and angiogenesis show many common features. In this study, we
      address the similarities between both transport systems, and focus in depth on
      the biology of lymphatic development. Based on the current advances in vascular
      regeneration, we propose different strategies for lymphatic tissue engineering
      that may be used for treatment of primary and secondary lymphedema.

PMID- 26204332
TI  - [On our own behalf: new rubric "Clinical Mini Standards" for primary care
      physicians and hospital physicians].

PMID- 26204331
TI  - A Double-Blind Placebo-Controlled Study of the Effects of Olprinone, a Specific
      Phosphodiesterase III Inhibitor, for Preventing Postoperative Atrial Fibrillation
      in Patients Undergoing Pulmonary Resection for Lung Cancer.
AB  - BACKGROUND: We previously reported that patients with elevated preoperative B
      type natriuretic peptide (BNP) levels have an increased risk for postoperative
      atrial fibrillation following lung cancer surgery. The present study evaluated
      whether the specific phosphodiesterase III inhibitor olprinone can reduce the
      incidence of postoperative atrial fibrillation in patients with elevated BNP
      levels undergoing pulmonary resection for lung cancer. METHODS: A prospective
      randomized study was conducted with 40 patients who had elevated preoperative BNP
      levels (>= 30 pg/mL) and underwent scheduled lung cancer surgery. All patients
      were in sinus rhythm at surgery. Low-dose olprinone or placebo was continuously
      infused for 24 h and started just before anesthesia induction. The primary end
      point was the incidence of postoperative atrial fibrillation. The secondary end
      points were perioperative hemodynamics and levels of BNP, WBC counts, and C
      reactive protein. RESULTS: The incidence of postoperative atrial fibrillation was
      significantly lower in the olprinone group than in the placebo group (10% vs 60%,
      P < .001). Patients in the olprinone group showed significantly lower BNP, WBC
      counts, and C-reactive protein levels after surgery. CONCLUSIONS: Continuous
      infusion of olprinone during lung cancer surgery was safe and reduced the
      incidence of postoperative atrial fibrillation following pulmonary resection in
      patients with elevated preoperative BNP levels. TRIAL REGISTRY: Japan Primary
      Registries Network; No.: JPRN-UMIN2404; URL: http://www.umin.ac.jp/ctr/.

PMID- 26204333
TI  - ["Outcome" or hopefully I can get out of this again!].

PMID- 26204334
TI  - [Direct acting oral anticoagulants in venous thromboembolism].

PMID- 26204336
TI  - [Factors Influencing the In-hospital Outcome of Injuries of the Upper Extremity].
AB  - Injuries of the upper extremity are frequent and are likely to increase in the
      future. This patient group is characterized by increased age and multimorbidity.
      The in-hospital outcome depends on various patient factors, such as advanced age,
      the severity of injury and the presence of relevant comorbidities, e.g. heart
      failure or atrial fibrillation. Next to patient factors, the effectiveness of
      care plays an important role. The treatment decision is complex and the
      interrater agreement is only moderate. Good anatomical knowledge and experience
      have a certain influence on the reliability. Random events can also contribute to
      the outcome.

PMID- 26204337
TI  - [Blood Pressure Lowering for Prevention and Treatment of Stroke: Recommendations
      of the Current European Guidelines].
AB  - Arterial hypertension is the most important modifiable risk factor for stroke. Up
      to 50% of all strokes may be attributable to hypertension. The risk of stroke is
      known to increase in a continuous fashion with a blood pressure (BP) of 115/75
      mmHg and higher. Patients with an abnormal circadian BP behavior also appear to
      be at risk. The benefit of antihypertensive drug therapy has been shown in both
      primary and secondary prevention of stroke. Generally, a BP target of under
      140/90 mmHg is recommended. BP lowering itself appears to be decisive rather than
      choice of the antihypertensive drug. In the acute phase of ischemic stroke and
      with some exceptions, BP should only be actively lowered at values over 220/120
      mmHg.

PMID- 26204338
TI  - [Stroke and Cancer: Are Cryptogenic Strokes a Paraneoplastic Syndrome?].
AB  - Cancer is an independent risk factor for ischemic stroke, and stroke can precede
      tumour diagnosis by many months. A paraneoplastic hypercoagulability has been
      implicated. Overall, cancer is a rare cause, but should be suspected in cases of
      cryptogenic stroke. In patients with cryptogenic stroke, two criteria - ischemic
      lesions in multiple vascular territories and D-dimer values >2,15 ug/ml - predict
      cancer with 100% specificity according to one relevant study. An adenocarcinoma
      at an advanced stage is identified in many cases, the risk of stroke-recurrence
      is high. There is a lack of evidence-based recommendations regarding secondary
      prevention in these cases. In analogy to the guidelines for venous
      thromboembolism in cancer patients, low molecular weight heparins might be more
      efficient compared to other anti-clotting agents.

PMID- 26204339
TI  - [Diastasis Recti Abdominis and Pregnancy].
AB  - Diastasis recti abdominis during pregnancy is a frequent phenomenon with a
      prevalence of 30-70%. It is associated with functional and cosmetic limitations.
      Gold standard in diagnosis during pregnancy is the transabdominal
      ultrasonography. The most frequent localization is in the periumbilical region
      and persistence postpartum is found in about 60% of cases. Either conservative or
      surgical treatments seem to be effective, but relapse rates, especially after
      surgical therapy, are unclear. It is a problem that no standard values of
      diastasis recti are given, no evidence-based therapy schemes are implemented and
      only rare and insufficient studies exist.

PMID- 26204341
TI  - [Early and intensive mobilization after stroke is no more effective than "usual
      care"].

PMID- 26204340
TI  - [Tick-borne illnesses - borreliosis and European tick-borne encephalitis].

PMID- 26204342
TI  - [Taking bisphosphonates is associated with a higher risk of atypical fractures].

PMID- 26204344
TI  - [CME - laboratory 41. Evaluating vitamin B12 status].

PMID- 26204347
TI  - Mucoadhesive nano-sized supramolecular assemblies for improved pre-corneal drug
      residence time.
AB  - CONTEXT: Mucoadhesive nanoparticles were compared with non-aggregated constituent
      polymers for effect on pre-corneal residence of dexamethasone phosphate (DP) or
      met-enkephalin (ME), administered by eye-drops to rabbits. OBJECTIVE: Deepening
      the knowledge of ophthalmic nanoparticulate systems in terms of ability to
      prolong pre-corneal residence. MATERIALS AND METHODS: Medicated nanoparticles
      resulted from gelation of quaternary ammonium-chitosan conjugate or its thiolated
      derivative with hyaluronan in the presence of drug. Particles were analyzed by
      light scattering. Dialysis removed non-encapsulated drug, dynamic dialysis
      measured drug-polymer interactions, and lyophilization-stabilized product.
      Dispersions were regenerated from lyophilized products. Also solutions of non
      thiolated or thiolated chitosan derivative were administered. Mean drug residence
      time (MRT) in tears was determined by collecting samples from lower marginal tear
      strip of albino rabbits using capillaries. RESULTS AND DISCUSSION: Nanoparticle
      size of regenerated dispersions was 400-430 nm (DP-systems), 360-370 nm (ME
      systems); the drug content was 2.5 mg/mL (DP) or 0.3 mg/mL (ME). The MRT for DP
      nanoparticles from non-thiolated derivative was higher than that for non
      aggregated polymer, due to stronger concurrent interactions of positively charged
      nanoparticles with ocular surface and drug. Thiolated polymer nanoparticles and
      non-aggregated parent polymer, both interacting weakly with DP, showed similar
      MRT values. The MRT of ME could only be enhanced by protecting drug from
      enzymatic hydrolysis. This was done by nanoparticle systems, whereas non
      aggregated polymers were ineffective. CONCLUSION: Developing a nanoparticle
      system rather than a solution of mucoadhesive polymer, for prolonging pre-corneal
      residence, is convenient, provided nanoparticles interact strongly with both
      ocular surface and drug, or protect drug from metabolic degradation.

PMID- 26204348
TI  - Rheological and textural properties of microemulsion-based polymer gels with
      indomethacin.
AB  - In this paper, we present novel microemulsion (ME)-based semisolid polymer gels
      designed for topical administration of poorly water soluble non-steroidal anti
      inflammatory drugs. Indomethacin (IND) was used as a model compound. The ME
      consisted of castor oil, water, Tween(r)80 as a surfactant and ethanol as
      cosurfactant. To obtain the desired consistency of the formulations
      Carbopol(r)960 was applied as a thickening agent. The aim of the study was to
      analyze in detail the mechanical properties of the obtained systems, with special
      attention paid to the features crucial for topical application. The rheological
      and textural experiments performed for samples with and without the incorporated
      drug clearly indicate that flow characteristics, viscoelastic properties and
      texture profiles were affected by the presence of IND. Novel semisolid
      formulations with IND described for the first time in this paper can be
      considered as an alternative for commercially available conventional topical
      dosage forms. 

PMID- 26204349
TI  - The influence of bile salts on the distribution of simvastatin in the
      octanol/buffer system.
AB  - INTRODUCTION: Distribution coefficient (D) is useful parameter for evaluating
      drugs permeability properties across biological membranes, which are of
      importance for drugs bioavailability. Given that bile acids are intensively
      studied as drug permeation-modifying and -solubilizing agents, the aim of this
      study was to estimate the influence of sodium salts of cholic (CA), deoxycholic
      (DCA) and 12-monoketocholic acids (MKC) on distribution coefficient of
      simvastatin (SV) (lactone [SVL] and acid form [SVA]) which is a highly lipophilic
      compound with extremely low water solubility and bioavailability. METHODS: LogD
      values of SVA and SVL with or without bile salts were measured by liquid-liquid
      extraction in n-octanol/buffer systems at pH 5 and 7.4. SV concentrations in
      aqueous phase were determined by HPLC-DAD. Chem3D Ultra program was applied for
      computation of physico-chemical properties of analyzed compounds and their
      complexes. RESULTS: Statistically significant decrease in both SVA and SVL logD
      was observed for all three studied bile salts at both selected pH. MKC exerted
      the most pronounced effect in the case of SVA while there were no statistically
      significant differences between observed bile salts for SVL. The calculated
      physico-chemical properties of analyzed compounds and their complexes supported
      experimental results. CONCLUSIONS: Our data indicate that the addition of bile
      salts into the n-octanol/buffer system decreases the values of SV distribution
      coefficient at both studied pH values. This may be the result of the formation of
      hydrophilic complexes increasing the solubility of SV that could consequently
      impact the pharmacokinetic parameters of SV and the final drug response in
      patients.

PMID- 26204350
TI  - High-resolution optical spectroscopy using multimode interference in a compact
      tapered fibre.
AB  - Optical spectroscopy is a fundamental tool in numerous areas of science and
      technology. Much effort has focused on miniaturizing spectrometers, but thus far
      at the cost of spectral resolution and broad operating range. Here we describe a
      compact spectrometer that achieves both high spectral resolution and broad
      bandwidth. The device relies on imaging multimode interference from leaky modes
      along a multimode tapered optical fibre, resulting in spectrally distinguishable
      spatial patterns over a wide range of wavelengths from 500 to 1,600 nm. This
      tapered fibre multimode interference spectrometer achieves a spectral resolution
      down to 40 pm in the visible spectrum and 10 pm in the near-infrared spectrum
      (corresponding to resolving powers of 10(4)-10(5)). Multimode interference
      spectroscopy is suitable in a variety of device geometries, including planar
      waveguides in a broad range of transparent materials.

PMID- 26204351
TI  - The effect of foetal movement counting on maternal anxiety: A randomised,
      controlled trial.
AB  - This study assessed the effect of foetal movement counting on maternal anxiety.
      In a randomised, controlled trial, 208 primigravida women with a singleton
      pregnancy were allocated either to perform daily foetal movement counting (n100)
      from 28 weeks ' gestation or to follow standard Iranian antenatal care (n108).
      Maternal anxiety was measured by Spielberger State-Trait Anxiety Inventory.
      Statistical analysis was performed by SPSS (16.0). There was no significant
      difference in mean state and trait anxiety scores at 28 weeks ' gestation; the
      difference was significant at 37 weeks ' gestation in state anxiety score between
      the intervention and control groups (35.34 9.98 vs. 38.25 9.63, respectively,
      P0.001). A significant difference was found in mean trait anxiety score at 37
      weeks ' gestation between the two groups (35.88 8.19 vs. 39.15 9.25,
      respectively, P 0.008). Women who performed foetal movement counting from 28 to
      37 weeks ' gestation reported less anxiety compared with those in control group.

PMID- 26204354
TI  - ?

PMID- 26204355
TI  - ?

PMID- 26204356
TI  - ?

PMID- 26204358
TI  - ?

PMID- 26204357
TI  - ?

PMID- 26204359
TI  - ?

PMID- 26204360
TI  - Human Adipose-Derived Mesenchymal Stem Cells Promote Liver Regeneration.
AB  - BACKGROUND AND AIMS: Liver regeneration (LR) is of crucial importance to patients
      with acute liver failure, those undergoing live donor liver transplantations or
      extended liver resections. Effective treatment strategies aimed at accelerating
      liver regeneration could offer major benefits in these patients. Due to easy
      accessibility, human adipose-derived mesenchymal stem cells (HADMSC) are an
      attractive source for regenerative medicine. Herein, we investigated the effect
      of HADMSC on LR in a murine model. We hypothesized that HADMSC will promote LR.
      METHODS: Mice were subjected to CCl4-induced acute liver failure (ALF). Animals
      in the experimental arm were treated with HADMSC prior to CCl4-induced ALF. Liver
      injury was evaluated using serum levels of alanine aminotransferase (ALT), serum
      interleukin-6 (IL-6), and histopathology. Liver samples were stained for a
      specific marker of regeneration, proliferating cell nuclear antigen (PCNA).
      RESULTS: Histology, serum IL-6, and ALT release revealed that HADMSC treatment
      attenuated liver injury compared with control animals. In addition, animals
      treated with HADMSC were observed to have improved survival and increased number
      of PCNA positive cells on histology when compared with controls. CONCLUSION:
      HADMSCs represent a potential therapeutic strategy to promote liver regeneration.

PMID- 26204361
TI  - Prediction of Quality of Life and Survival After Surgery for Symptomatic Spinal
      Metastases: A Multicenter Cohort Study to Determine Suitability for Surgical
      Treatment.
AB  - BACKGROUND: Surgery for symptomatic spinal metastases aims to improve quality of
      life, pain, function, and stability. Complications in the postoperative period
      are not uncommon; therefore, it is important to select appropriate patients who
      are likely to benefit the greatest from surgery. Previous studies have focused on
      predicting survival rather than quality of life after surgery. OBJECTIVE: To
      determine preoperative patient characteristics that predict postoperative quality
      of life and survival in patients who undergo surgery for spinal metastases.
      METHODS: In a prospective cohort study of 922 patients with spinal metastases who
      underwent surgery, we performed preoperative and postoperative assessment of
      EuroQol EQ-5D quality of life, visual analog score for pain, Karnofsky physical
      functioning score, complication rates, and survival. RESULTS: The primary tumor
      type, number of spinal metastases, and presence of visceral metastases were
      independent predictors of survival. Predictors of quality of life after surgery
      included preoperative EQ-5D (P = .002), Frankel score (P < .001), and Karnofsky
      Performance Status (P < .001). CONCLUSION: Data from the largest prospective
      surgical series of patients with symptomatic spinal metastases revealed that
      tumor type, the number of spinal metastases, and the presence of visceral
      metastases are the most useful predictors of survival and that quality of life is
      best predicted by preoperative Karnofsky, Frankel, and EQ-5D scores. The
      Karnofsky score predicts quality of life and survival and is easy to determine at
      the bedside, unlike the EQ-5D index. Karnofsky score, tumor type, and spinal and
      visceral metastases should be considered the 4 most important prognostic
      variables that influence patient management.

PMID- 26204362
TI  - Current opinion: the management of tinnitus.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe our experience with
      management of chronic tinnitus and to review the recent literature on the best
      treatment options available for treating patients who are troubled by their
      tinnitus. In addition, we want to highlight our experience and approach to this
      very common problem. RECENT FINDINGS: Treatment options for patients are based on
      the severity of the tinnitus and any associated problems. The use of nutritional
      supplements has a place in the treatment of mild-to-moderate tinnitus. Ginkgo
      biloba and B-complex vitamins may have an impact on selected patients. Treatment
      of underlying or accompanying anxiety disorders especially with cognitive
      behavior therapy can help to reduce the distress associated with tinnitus.
      Surgical treatment options, such as cochlear implant, have been shown to be very
      effective in reducing tinnitus in patients with sudden unilateral hearing loss as
      the cause of tinnitus. Other surgical approaches, such as repetitive transcranial
      magnetic stimulation and vagal stimulator, have had some limited benefits.
      SUMMARY: Treatment for subjective tinnitus can range from the conventional to the
      investigational modalities. Best treatment options take into account the possible
      cause of the tinnitus and other associated symptoms.

PMID- 26204363
TI  - A survey of current practices and preferences for internal fixation of displaced
      olecranon fractures.
AB  - BACKGROUND: Olecranon fractures represent 10% of upper extremity fractures. There
      is a growing body of literature to support the use of plate fixation for
      displaced olecranon fractures. The purpose of this survey was to gauge Canadian
      surgeons' practices and preferences for internal fixation methods for displaced
      olecranon fractures. METHODS: Using an online survey tool, we administered a
      cross-sectional survey to examine current practice for fixation of displaced
      olecranon fractures. RESULTS: We received 256 completed surveys for a response
      rate of 31% (95% confidence interval [CI] 30.5-37.5%). The preferred treatment
      was tension band wiring (78.5%, 95% CI 73-83%) for simple displaced olecranon
      fractures (Mayo IIA) and plating (81%, 95% CI 75.5-85%) for displaced comminuted
      olecranon fractures (Mayo IIB). Fracture morphology with a mean impact of 3.31
      (95% CI 3.17-3.45) and comminution with a mean impact of 3.34 (95% CI 3.21-3.46)
      were the 2 factors influencing surgeons' choice of fixation method the most. The
      major deterrent to using tension band wiring for displaced comminuted fractures
      (Mayo IIB) was increased stability obtained with other methods described by 75%
      (95% CI 69-80%) of respondents. The major deterrent for using plating constructs
      for simple displaced fractures (Mayo IIA) was better outcomes with other methods.
      Hardware prominence was the most commonly perceived complication using either
      method of fixation: 77% (95% CI 71.4-81.7%) and 76.2% (95% CI 70.6-81.0%) for
      tension band wiring and plating, respectively. CONCLUSION: Divergence exists with
      current literature and surgeon preference for fixation of displaced olecranon
      fractures.

PMID- 26204365
TI  - Laparoscopic-assisted percutaneous endoscopic gastrostomy: insertion of a skin
      level device using a tear-away sheath.
AB  - BACKGROUND: This study describes our experience with the placement of a skin
      level gastrostomy device (MIC-KEY) in a single procedure. METHODS: We identified
      infants, children and young adults who underwent laparoscopic-assisted
      percutaneous endoscopic gastrostomy (LAPEG) tube insertion between October 2009
      and June 2013. The steps of this procedure include upper endoscopy, single-port
      laparoscopy, gastropexy via percutaneous T-fasteners and placement of a skin
      level gastrostomy device (MIC-KEY) using a "push" technique with a tear-away
      sheath. RESULTS: We included 92 patients in our study. Mean age was 3.7 years
      (range 3 wk-5 yr), and mean weight was 11.2 (range 2.8-54) kg. Median procedural
      time was 20 (range 12-76) minutes. Total median duration for the most recent 25
      procedures was lower than that of the first 25 (62 v. 79 min, p = 0.004). There
      were no intraoperative complications or conversions to open surgery.
      Postoperative complications were observed in 6 (6.5%) patients. Three retained T
      fasteners were assessed endoscopically (n = 1) or removed via local excision (n =
      2). Two patients experienced early dislodged feeding tubes that were replaced via
      interventional radiology (n = 1) or repeat LAPEG (n = 1). There was also 1 intra
      abdominal fluid collection that was drained percutaneously but ultimately
      required a laparotomy and washout. There were no major complications in the most
      recent 50 procedures. CONCLUSION: Our results suggest that LAPEG is a safe,
      minimally invasive procedure for infants, children and young adults. This
      approach allows for immediate use of a skin-level gastrostomy device without the
      need for postoperative tube exchanges.

PMID- 26204364
TI  - Reduced time to surgery improves mortality and length of stay following hip
      fracture: results from an intervention study in a Canadian health authority.
AB  - BACKGROUND: Existing literature demonstrating the negative impact of delayed hip
      fracture surgery on mortality consists largely of observational studies prone to
      selection bias and may overestimate the negative effects of delay. We conducted
      an intervention study to assess initiatives aimed at meeting a 48-hour benchmark
      for hip fracture surgery to determine if the intervention achieved a reduction in
      time to surgery, and if a general reduction in time to surgery improved mortality
      and length of stay. METHODS: We compared time to surgery, length of stay and
      mortality between pre- and postintervention patients with a hip fracture using
      the Kaplan-Meier estimator and Cox proportional hazards model adjusting for age,
      sex, comorbidities, type of surgery and year. RESULTS: We included 3525 pre- and
      3007 postintervention patients aged 50 years or older. The proportion of patients
      receiving surgery within the benchmark increased from 66.8% to 84.6%, median
      length of stay decreased from 13.5 to 9.7 days, and crude in-hospital mortality
      decreased from 9.6% to 6.8% (all p < 0.001). Adjusted analyses revealed reduced
      mortality in hospital (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.57
      0.81) and at 1 year (HR 0.87, 95%CI 0.79-0.96). Independent of the intervention
      period, having surgery within 48 hours demonstrated decreased adjusted risk of
      death in hospital (HR 0.51, 95%CI 0.41-0.63) and at 1 year postsurgery (HR 0.72,
      95% CI 0.64-0.80). CONCLUSION: Coordinated, region-wide efforts to improve
      timeliness of hip fracture surgery can successfully reduce time to surgery and
      appears to reduce length of stay and adjusted mortality in hospital and at 1
      year.

PMID- 26204366
TI  - Initial assessment of patient handoff in accredited general surgery residency
      programs in the United States and Canada: a cross-sectional survey.
AB  - BACKGROUND: Communication errors are considered one of the major causes of
      sentinel events. Our aim was to assess the process of patient handoff among
      junior surgical residents and to determine ways in which to improve the handoff
      process. METHODS: We conducted nationwide surveys that included all accredited
      general surgery residency programs in the United States and Canada. RESULTS: Of
      the 244 American and 17 Canadian accredited surgical residency programs
      contacted, 65 (27%) and 12 (71%), respectively, participated in the survey. Of
      the American and Canadian respondents, 66% and 69%, respectively, were from
      postgraduate year (PGY) 1, and 32% and 29%, respectively, were from PGY 2; 85
      (77%) and 50 (96%), respectively, had not received any training about patient
      handoff before their surgical residency, and 27% and 64%, respectively, reported
      that the existing handoff system at their institutions did not adequately protect
      patient safety. Moreover, 29% of American respondents and 37% of Canadian
      respondents thought that the existing handoffs did not support continuity of
      patient care. Of the American residents, 67% and 6% reported receiving an
      incomplete handoff that resulted in minor and major patient harm, respectively.
      These results mirrored those from Canadian residents (63% minor and 7% major
      harm). The most frequent factor reported to improve the patient handoff process
      was standardization of the verbal handoff. CONCLUSION: Our survey results
      indicate that the current patient handoff system contributes to patient harm.
      More efforts are needed to establish standardized forms of verbal and written
      handoff to ensure patient safety and continuity of care.

PMID- 26204367
TI  - Rehabilitation after lower limb injury: development of a predictive score (RALLI
      score).
AB  - BACKGROUND: The purpose of our study was to identify the risk factors associated
      with the need for inpatient rehabilitation after lower limb injury to develop a
      predictive scoring tool for early identification of such patients. METHODS: We
      followed a prospective cohort of patients admitted to a level 1 trauma centre.
      Data were collected through chart review and a self-administered questionnaire on
      sociodemographics, patient living environment, pretrauma status, injury and
      treatment received. We compared patients who were discharged home with those
      going to rehabilitation after acute care. Analysis consisted of bivariate
      comparisons and logistic regression. RESULTS: Our study included 160 patients
      with a mean age of 56 years. A total of 40% were discharged to an inpatient
      rehabilitation centre. Factors associated with inpatient rehabilitation were low
      preinjury physical health status, concomitant injury of the upper limbs,
      bilateral lower limb injury, the use of a walking aid before injury, head injury
      and femur or pelvic fractures. We created a predictive score using the top 3 risk
      factors: upper limb injury, bilateral lower limb injury and presence of femoral
      or pelvic fractures. The chance of needing inpatient rehabilitation rose from 14%
      with 0 factors to 47% with 1 factor and 96% with 2 factors. CONCLUSION:
      Rehabilitation planning should begin for patients exhibiting at least of 3 risk
      factors at the time of admission to acute care. Prospective validation of the
      tool is needed, but it has the potential to orient the multidisciplinary team's
      decision on rehabilitation needs postdischarge.

PMID- 26204368
TI  - 15th Bethune Round Table Conference on International Surgery Abstracts.

PMID- 26204369
TI  - 2015 Canadian Surgery Forum Abstracts.

PMID- 26204370
TI  - Raising the standard of surgical reporting to increase its impact.

PMID- 26204372
TI  - A tribute to Lloyd D. MacLean.
AB  - Dr. Lloyd D. MacLean, long-time co-editor of the Canadian Journal of Surgery
      passed away earlier this year at the age of 90. In order to appreciate the
      contributions of Dr. MacLean to the journal, this commentary recognizes him as a
      humble surgeon-scientist who was one of - if not the - most outstanding Canadian
      ambassadors to academic surgery in North America.

PMID- 26204373
TI  - In memory of Lloyd D. MacLean.
AB  - Canadian surgery has lost one of its great leaders. Dr. Lloyd Douglas MacLean
      died in his sleep on Jan. 14, 2015, at 90 years of age. This commentary
      highlights his contributions to Canadian surgery.

PMID- 26204374
TI  - Transformational Nurse Leaders Key to Strengthening Health Systems Worldwide.
AB  - This column, presented by the director of the International Council of Nurses
      (ICN), discusses the work of the ICN over the past 20 years and into the future
      in developing nursing leaders across the globe. Dr Ferguson relates this activity
      to the constructs of the Magnet Recognition Program. The ICN is at the forefront
      of making sure nurses and nurse executives have the knowledge, skills, and
      ability to lead effectively worldwide and meet the global health challenges.

PMID- 26204375
TI  - Enhancing Cross-functional Collaboration and Effective Problem Solving Through an
      Innovation Challenge for Point-of-Care Providers.
AB  - An internal employee challenge competition is a way to promote staff engagement
      and generate innovative business solutions. This Spotlight on Leadership focuses
      on the approach that a large not-for-profit healthcare organization, the Visiting
      Nurse Service of New York, took in designing and executing an innovation
      challenge. The challenge leveraged internal staff expertise and promoted wide
      participation. This model is 1 that can be replicated by organizations as leaders
      work to engage employees at the point of service in organization-wide problem
      solving. 

PMID- 26204376
TI  - The American Organization of Nurse Executives and Emergency Nurses Association
      Guiding Principles on Mitigating Violence in the Workplace.
AB  - Violence in the workplace, including violence toward staff from patients and
      families as well as lateral violence, has become a serious safety issue for
      hospitals in the United States. Concerned about this issue, the Emergency Nurses
      Association and the American Organization of Nurse Executives convened a Day of
      Dialogue to discuss ways to mitigate violence in the workplace. The result of the
      discussion was the development of guiding principles and a toolkit to assist
      nurse leaders in systemically reducing lateral violence and patient and family
      violence in hospitals. 

PMID- 26204377
TI  - Financial Proposals: What Nurse Executives Need to Know.
AB  - Presenting a successful financial proposal requires attention to the specific
      needs and expectations of financial decision makers. This may require challenging
      preconceived notions, beliefs, and assumptions the requester may have about what
      is important. The author reviews key concepts and suggestions for nurse
      executives requesting financial resources. 

PMID- 26204378
TI  - The Relationship of Workplace Culture With Nursing-Sensitive Organizational
      Factors.
AB  - OBJECTIVE: The aim of this study is to explore the relations of workplace culture
      on nursing-sensitive organizational factors. BACKGROUND: The need for
      standardized and valid measures for nursing-sensitive organizational outcomes has
      already been recognized in the literature. METHODS: A cross-sectional
      questionnaire survey of 21 inpatient acute care units in 9 organizations at the
      municipal primary healthcare level was conducted. Participants included licensed
      practical nurses, registered nurses, and nurse managers. RESULTS: Workplace
      culture, especially the overarching factor of stress, correlated with the use of
      supplemental nursing staff and patients' length of stay. CONCLUSION: It is
      essential to find and test workplace-sensitive indicators so that managers will
      have a wider range of methods to plan and evaluate nursing outcomes.

PMID- 26204379
TI  - Political Skill and Its Relevance to Nursing: An Integrative Review.
AB  - OBJECTIVE: The aim of this study was to conduct an integrative analysis of
      literature for the concept of political skill and relevance to nursing.
      BACKGROUND: Political skill has been extensively studied in organizational
      psychology for several decades but limited in the nursing literature. METHODS:
      Inclusion criteria were literature reviews, primary qualitative, quantitative,
      and mixed-methods studies written in English between 2000 and 2014, with 147
      articles being identified. RESULTS: Of 147 articles, 38 met criteria by defining
      political skill as the ability to effectively understand others at work and to
      use such knowledge to influence others to act in ways that enhance personal
      and/or organizational goals. CONCLUSIONS: Political skill influences leadership
      and an individual's ability to navigate organizational politics, performance
      evaluation, interpersonal skills, networking ability, stress level, and social
      capital in the work environment.

PMID- 26204380
TI  - Creating a Culture of Rapid Change Adoption: Implementing an Innovations Unit.
AB  - This article provides an overview of 1 hospital's efforts to proactively identify
      and test new approaches to care delivery through the creation of an Innovations
      Unit, including the structure and processes of the initiative, the outcomes
      achieved, and the lessons learned. 

PMID- 26204381
TI  - Development of an Instrument to Measure Civil and Uncivil Behaviors in the
      Hospital Clinical Environment: Implications for Nurse Leaders.
AB  - OBJECTIVE: The purpose of this study is to develop a valid and reliable
      instrument to measure nursing students' (NSs') perceptions of civil and uncivil
      behaviors displayed by direct care nurses in the hospital clinical environment.
      BACKGROUND: Incivility in nursing has been well documented. However, little is
      known about perceptions of incivility by NSs in the hospital clinical environment
      and its effects on NSs' transition to professional practice. METHODS: A 13-item
      instrument was developed using literature, faculty feedback, and a semistructured
      focus group. The instrument was administered to convenience samples of NSs at a
      Midwest, Magnet-designated pediatric hospital (N = 496). RESULTS: Findings
      indicated high reliability and validity of the instrument, with a Cronbach's
      alpha of .930. CONCLUSIONS: This study has produced a valid and reliable survey
      instrument to measure the perception of civil and noncivil behaviors on the part
      of clinical nurses as rated by NSs in hospital clinical settings. The use of this
      instrument will be beneficial to nurse executives in measuring these perceptions
      in their clinical settings.

PMID- 26204382
TI  - The Importance of Biodiversity E-infrastructures for Megadiverse Countries.
AB  - Addressing the challenges of biodiversity conservation and sustainable
      development requires global cooperation, support structures, and new governance
      models to integrate diverse initiatives and achieve massive, open exchange of
      data, tools, and technology. The traditional paradigm of sharing scientific
      knowledge through publications is not sufficient to meet contemporary demands
      that require not only the results but also data, knowledge, and skills to analyze
      the data. E-infrastructures are key in facilitating access to data and providing
      the framework for collaboration. Here we discuss the importance of e
      infrastructures of public interest and the lack of long-term funding policies. We
      present the example of Brazil's speciesLink network, an e-infrastructure that
      provides free and open access to biodiversity primary data and associated tools.
      SpeciesLink currently integrates 382 datasets from 135 national institutions and
      13 institutions from abroad, openly sharing ~7.4 million records, 94% of which
      are associated to voucher specimens. Just as important as the data is the network
      of data providers and users. In 2014, more than 95% of its users were from
      Brazil, demonstrating the importance of local e-infrastructures in enabling and
      promoting local use of biodiversity data and knowledge. From the outset,
      speciesLink has been sustained through project-based funding, normally public
      grants for 2-4-year periods. In between projects, there are short-term crises in
      trying to keep the system operational, a fact that has also been observed in
      global biodiversity portals, as well as in social and physical sciences platforms
      and even in computing services portals. In the last decade, the open access
      movement propelled the development of many web platforms for sharing data.
      Adequate policies unfortunately did not follow the same tempo, and now many
      initiatives may perish. 

PMID- 26204384
TI  - Review of Burn Research for Year 2014.
AB  - Management of burn injuries requires treatments and interventions from many
      disciplines. Worldwide, burn patients suffer from physical and psychological
      challenges that impact their lives socially and economically. In this review, we
      will highlight a handful of the numerous articles published in multiple areas of
      burn care. The areas of burn care addressed in the article are: epidemiology;
      burn resuscitation, critical care, and infection; nutrition and metabolism; pain
      and rehabilitation; prevention and firefighter safety; psychology; and
      reconstruction and wounds. 

PMID- 26204383
TI  - Proteasome Inhibition After Burn Injury.
AB  - The objective of this study was to assess the effects of proteasome inhibition on
      the development of burn-induced hypermetabolism. Rats underwent 30-40% total BSA
      scald burn or sham injury. The proteasome inhibitor bortezomib (0.1 mg/kg) or
      vehicle (n = 10) was administered i.p. 3* weekly starting at 2 hours (early
      bortezomib, n = 20) or 48 hours (late-bortezomib, n = 13) postburn. Body weights
      were determined weekly. Resting energy expenditures (REE) were measured at days 0
      (baseline), 7, 14, 21, and 42 postburn. At day 42, blood and pectoral muscle were
      harvested. Routine blood chemistry parameters were analyzed. Proteasome content,
      proteasome peptidase activities, and ubiquitin-protein conjugates were measured
      in muscle extracts. As compared with sham-vehicle-treated animals, specific
      proteasome activities were increased after burn and vehicle treatment. Bortezomib
      treatment inhibited proteasome activities and increased ubiquitin-protein
      conjugates after sham and burn injury. Bortezomib treatment did not affect REE
      after sham procedure. REE significantly increased by 47% within 7 days and
      remained elevated until day 42 after burn and vehicle treatment. After early
      bortezomib treatment, burn-induced increases in REE were delayed and
      significantly reduced by 42% at day 42, as compared with vehicle treatment. With
      late-bortezomib treatment, burn-induced increases in REE were also delayed but
      not attenuated at day 42. Mortality was 20% with vehicle, 65% (median survival
      time: 1.875 days) with early-bortezomib and 25% with late-bortezomib treatment
      after burns (P < .05 early-bortezomib vs vehicle and late-bortezomib). Proteasome
      inhibition delays development of burn-induced hypermetabolism. Although
      proteasome inhibition early after burn injury reduces the hypermetabolic
      response, it significantly increases early burn-associated mortality.

PMID- 26204386
TI  - Re: A Primer on Pigmentation.

PMID- 26204385
TI  - Ubiquitin Urine Levels in Burn Patients.
AB  - The objective of this study was to determine whether urine ubiquitin levels are
      elevated after burns and to assess whether urine ubiquitin could be useful as a
      noninvasive biomarker for burn patients. Forty burn patients (%TBSA: 20 +/- 22;
      modified Baux scores: 73 +/- 26) were included (control: 11 volunteers). Urine
      was collected in 2-hour intervals for 72 hours, followed by 12-hour intervals
      until discharge from the intensive care unit. Ubiquitin concentrations were
      analyzed by enzyme linked immunosorbent assay and Western blot. Total protein was
      determined with a Bradford assay. Patient characteristics and clinical parameters
      were documented. Urine ubiquitin concentrations, renal ubiquitin excretion, and
      excretion rates were correlated with patient characteristics and outcomes.
      Initial urine ubiquitin concentrations were 362 +/- 575 ng/ml in patients and 14
      +/- 18 ng/ml in volunteers (P < .01). Renal ubiquitin excretion on day 1 was
      292.6 +/- 510.8 MUg/24 hr and 21 +/- 27 MUg/24 hr in volunteers (P < .01).
      Initial ubiquitin concentrations correlated with modified Baux scores (r = .46; P
      = .02). Ubiquitin levels peaked at day 6 postburn, whereas total protein
      concentrations and serum creatinine levels remained within the normal range.
      Total renal ubiquitin excretion and excretion rates were higher in patients with
      %TBSA >=20 than with %TBSA <20, in patients who developed sepsis/multiple organ
      failure than in patients without these complications and in nonsurvivors vs
      survivors. These data suggest that ubiquitin urine levels are significantly
      increased after burns. Renal ubiquitin excretion and/or excretion rates are
      associated with %TBSA, sepsis/multiple organ failure, and mortality. Although
      these findings may explain previous correlations between systemic ubiquitin
      levels and outcomes after burns, the large variability of ubiquitin urine levels
      suggests that urine ubiquitin will not be useful as a noninvasive disease
      biomarker.

PMID- 26204387
TI  - Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral
      Nerve Blocks.
AB  - BACKGROUND: Liposome bupivacaine (Exparel) is a multivesicular liposomal
      formulation of bupivacaine currently approved in the United States for single
      dose administration into the surgical site to provide postsurgical analgesia.
      This retrospective analysis examined safety data from clinical trials involving
      the off-label use of this formulation in peripheral nerve blocks. METHODS: Data
      from 6 controlled (phases I-III) studies were compiled involving single-injection
      ankle, femoral nerve, and intercostal nerve blocks (2 each). Adverse events (AEs)
      were monitored for 1 to 30 days after study drug administration. RESULTS: Of 575
      subjects, 335 received liposome bupivacaine (2-310 mg), 33 received bupivacaine
      HCl (75-125 mg), and 207 received normal saline (placebo). Overall, 76% of
      subjects receiving liposome bupivacaine experienced 1 or more AEs compared with
      61% receiving bupivacaine HCl and 76% receiving placebo. The most frequently
      reported AEs among subjects receiving liposome bupivacaine were nausea, pyrexia,
      pruritus, constipation, and vomiting. The most common treatment-related AE was
      hypesthesia among subjects treated with liposome bupivacaine or bupivacaine HCl.
      Incidence of nervous system AEs for liposome bupivacaine, bupivacaine HCl, and
      placebo was 21%, 27%, and 21%, respectively. Similarly, incidence of cardiac AEs
      was 9%, 0%, and 12%, respectively. At least 1 serious AE occurred in 8% of
      subjects receiving liposome bupivacaine compared with 10% of those receiving
      placebo (none assessed by investigators as related to study medication).
      CONCLUSIONS: Liposome bupivacaine has a similar safety and side effect profile to
      bupivacaine HCl and normal saline, suggesting that most of the more common AEs
      are related to either opioid rescue or the surgical procedure itself.

PMID- 26204389
TI  - Concurrent high-sensitivity conductometric detection of volatile weak acids in a
      suppressed anion chromatography system.
AB  - A suppressed hydroxide eluent anion chromatograph effluent flows through the
      outside of a gas-permeable membrane tube while electrogenerated 100-200 MUM LiOH
      flows through the lumen into a second conductivity detector. Undissociated
      volatile acid eluites (e.g., H2S, HCN, H2CO3, etc., represented as HA) transfer
      through the membrane and react as OH(-) + HA -> A(-) + H2O; the conversion of
      high-mobility OH(-) to lower mobility A(-) results in a significant negative
      response for these analytes. With the chromatograph operated at a macroscale (0.3
      mL/min) the LiOH flow can be 3-30-fold lower, resulting in corresponding
      enrichment of the transferred analyte prior to detection. Because there is no
      mixing of liquids, the detector noise is very low (<0.1 nS/cm), comparable to the
      principal chromatographic detector. Thus, despite a background of 25-45 MUS/cm,
      limits of detection for sulfide and cyanide are in the submicromolar level, with
      a linear dynamic range up to 100 MUM. Carbonate/bicarbonate can also be
      sensitively detected. We demonstrate adaptation in a standard commercial system.
      We also show that Microsoft Excel-based numerical simulations of transport
      quantitatively predict the observed behavior well. 

PMID- 26204388
TI  - Rotational Thromboelastometry-Guided Hemostatic Therapy for Management of
      Cerebrospinal Fluid Catheter in Patients Undergoing Endovascular Aortic Repair.
AB  - OBJECTIVE: Central neuraxial techniques are typically avoided in patients with
      underlying coagulopathy or abnormal coagulation tests. Vertebral canal hematoma
      is a rare but devastating complication of those procedures. Although the
      sensitivity and specificity of standard laboratory tests in predicting this event
      are rather poor or unknown, these tests are commonly used to allow or advise
      against the insertion of an epidural or spinal catheter. Furthermore, the role of
      viscoelastic point-of-care tests, which are widely used to monitor coagulation in
      the perioperative setting, is unexplored. CASE REPORT: We report a patient
      presenting for endovascular repair of a dissecting thoracoabdominal aortic
      aneurysm, in which we placed a subarachnoid catheter for continuous cerebrospinal
      fluid drainage because of the high risk of spinal cord ischemia associated with
      the procedure. Unfortunately, the patient presented with an overt consumption
      coagulopathy that would have advised against performing any central neuraxial
      technique. Bedside monitoring, diagnosis, and goal-directed hemostatic therapy
      guided by thromboelastometry documented improved coagulation both at the time of
      insertion and removal of the subarachnoid device. No catheter-related
      complications occurred. CONCLUSIONS: Thromboelastometry proved useful to guide
      hemostatic therapy before subarachnoid catheter placement and extraction in a
      patient with severe coagulopathy when standard coagulation tests were of less
      benefit.

PMID- 26204390
TI  - Identification of drought-induced transcription factors in Sorghum bicolor using
      GO term semantic similarity.
AB  - Stress tolerance in plants is a coordinated action of multiple stress response
      genes that also cross talk with other components of the stress signal
      transduction pathways. The expression and regulation of stress-induced genes are
      largely regulated by specific transcription factors, families of which have been
      reported in several plant species, such as Arabidopsis, rice and Populus. In
      sorghum, the majority of such factors remain unexplored. We used 2DE refined with
      MALDI-TOF techniques to analyze drought stress-induced proteins in sorghum. A
      total of 176 transcription factors from the MYB, AUX_ARF, bZIP, AP2 and WRKY
      families of drought-induced proteins were identified. We developed a method based
      on semantic similarity of gene ontology terms (GO terms) to identify the
      transcription factors. A threshold value (>= 90%) was applied to retrieve total
      1,493 transcription factors with high semantic similarity from selected plant
      species. It could be concluded that the identified transcription factors regulate
      their target proteins with endogenous signals and environmental cues, such as
      light, temperature and drought stress. The regulatory network and cis-acting
      elements of the identified transcription factors in distinct families are
      involved in responsiveness to auxin, abscisic acid, defense, stress and light.
      These responses may be highly important in the modulation of plant growth and
      development. 

PMID- 26204391
TI  - Evaluation of the potential of alkylresorcinols as superoxide anion scavengers
      and sox-regulon modulators using nitroblue tetrazolium and bioluminescent cell
      based assays.
AB  - The antioxidant activities of five alkylresorcinol (AR) homologs with alkyl
      chains of 1, 3, 5 6 and 12 carbon atoms were studied using molecular and cellular
      assays for superoxide anions (O2.-). The effect of ARs as superoxide anion
      scavengers was assessed using the photochemical reaction of spontaneous photo
      reduced flavin re-oxidation. In this system, ARs reaction with O2.- produced dye
      derivatives, as C6- and C12-AR prevented the O2.--induced conversion of nitroblue
      tetrazolium into formazan in AR-containing mixtures. The influence of ARs on soxS
      gene expression and bacterial cell viability was studied with the luminescent
      Escherichia coli K12 MG1655 psoxS'::luxCDABE-AmpR strain, showing low basal light
      emission. This increased significantly during paraquatinduced oxidative stress as
      a consequence of the simultaneous transcription of soxS-gene and lux-gene fusion.
      ARs with alkyl chains containing 5-12 carbon atoms at concentrations of 0.1-1.0
      MUM weakly induced soxS-gene expression, whereas 1-10 mM repressed it. This
      respectively increased or decreased the bacterial cell resistance to O2.- 
      related oxidative stress. AR derivatives lost their protective activity from
      reactions with superoxide anions, which required increased soxS gene expression
      for cell viability. These results show the dual nature of ARs, which possess
      direct antioxidant properties and the ability to indirectly regulate the activity
      of cellular antioxidative defense mechanisms. 

PMID- 26204392
TI  - Cyclic phosphatidic acid induces G0/G1 arrest, inhibits AKT phosphorylation, and
      downregulates cyclin D1 expression in colorectal cancer cells.
AB  - Lysophosphatidic acid (LPA) and its analogs are well-known mitogens for various
      cell types. Many reports have confirmed that several types of cancer cell produce
      LPA to promote survival, growth and tumorigenesis. This indicates that the
      interface between the LPA signaling pathway and the cell cycle signaling system
      is critical to the control of cancer cell proliferation. However, our previous
      study indicated that cyclic phosphatidic acid (cPA), which is structurally
      similar to LPA, inhibits the proliferation and migration of colon cancer cells.
      It has been reported that cPA shows several biological activities not shown by
      LPA. However, understanding of the detailed molecular and cellular mechanism
      underlying the regulation of the cell cycle by cPA is still in its infancy. In
      this study, we investigated the effect of cPA treatment on human DLD-1 colon
      cancer cells by analyzing cell cycle dynamics, gene expression, and AKT
      phosphorylation. Our findings indicate that cPA inhibits cell cycle progression
      in DLD-1 colon cancer cells via the downregulation of cyclin D1 and the
      inhibition of AKT phosphorylation. 

PMID- 26204393
TI  - Polymorphism of the APEX nuclease 1 gene in keratoconus and Fuchs endothelial
      corneal dystrophy.
AB  - Human APEX nuclease 1 (APEX1) plays an important role in the repair of oxidative
      DNA lesions through base excision repair. It may influence the development of
      oxidative stress-related diseases. The aim of this study was to determine the
      relationship between the genotypes of the c.444 T>G (rs1130409) and c.-468 T>G
      (rs1760944) polymorphisms in the APEX1 gene and the occurrence of two oxidative
      stress-related eye diseases: keratoconus (KC) and Fuchs endothelial corneal
      dystrophy (FECD). The study involved 250 patients with KC, 209 patients with
      FECD, and 350 control subjects. All of the patients and control subjects
      underwent a detailed ophthalmic examination. The polymorphisms were genotyped by
      mismatch polymerase chain reaction restriction fragment length polymorphism
      (mismatch PCR-RFLP). We observed that the G/T and T/T genotypes of the c.-468 T>G
      polymorphism were respectively associated with a decreased occurrence of KC (OR
      0.54, 95% CI 0.37-0.95; p = 0.030) and an increased occurrence of KC (OR 1.87,
      95% CI 1.06-3.32; p = 0.032). None of these polymorphisms showed any association
      with FECD. Furthermore, no other association was observed, including haplotypes
      of the two polymorphisms. Our findings suggest that the c.-468 T>G polymorphism
      of the APEX1 gene may play a role in the pathogenesis of KC. 

PMID- 26204394
TI  - FE65: Roles beyond amyloid precursor protein processing.
AB  - FE65 is a brain-enriched, developmentally regulated adaptor protein that was
      first identified as a binding partner of amyloid precursor protein (APP), an
      important molecule in Alzheimer's disease. FE65 possesses three protein
      interaction domains, including an N-terminal WW domain and two C-terminal
      phosphotyrosine-binding (PTB) domains. It is capable of mediating the assembly of
      multimolecular complexes. Although initial work reveals its roles in APP
      processing and gene transactivation, increasing evidence suggests that FE65
      participates in more diverse biological processes than originally anticipated.
      This article discusses the role of FE65 in signal transduction during cell stress
      and protein turnover through the ubiquitin-proteasome system and in various
      neuronal processes, including neurogenesis, neuronal migration and positioning,
      neurite outgrowth, synapse formation and synaptic plasticity, learning, and
      memory. 

PMID- 26204395
TI  - Single nucleotide polymorphisms in the STAT3 gene influence AITD susceptibility,
      thyroid autoantibody levels, and IL6 and IL17 secretion.
AB  - STAT3 (signal transducer and activator of transcription 3) is an important
      cellular effector in the Jak/STAT signaling pathway, which plays a pivotal role
      in human immune system regulation, mediating the effect of different cytokines.
      In the present study, we assessed the correlation between STAT3 polymorphisms
      (rs3816769 C>T and rs744166 A>G) and risk of the autoimmune thyroid diseases
      (AITDs) Hashimoto's thyroiditis (HT) and Graves' disease (GD) in the Polish
      population. Moreover, we evaluated the association of polymorphisms with the
      thyroid autoantibody levels (TPOAb, TgAb, TRAb) and the correlation between
      circulating proinflammatory IL6 and IL17 cytokines and thyroid autoantibody
      levels. The study included 71 AITD patients with HT (n = 39) or GD (n = 32) and a
      control group (n = 40). DNA SNP genotyping was performed using TaqMan probes.
      Serum levels of thyroid autoantibodies, IL6 and IL17 were measured according to
      enhanced chemiluminescence (ECL) assay. Allele A of STAT3 SNP rs744166 A>G was
      significantly more frequent in both HT and GD patients, while allele G was
      significantly more frequent in the control group. Similarly, allele C and CC
      genotype of STAT3 SNP rs3816769 C>T were significantly more frequent in the
      control group in comparison to HT and GD patients. Significantly higher TgAb
      median values were associated with CT rs3816769 genotype in HT patients. Serum
      levels of IL6 and IL17 positively correlated with TPOAb in the HT group. Serum
      level of IL6 positively correlated with TPOAb in the AITD group. Both studied
      polymorphisms seem to play a significant role in susceptibility to AITD (HT and
      GD). STAT3 SNPs may influence TAb level in AITD patients. 

PMID- 26204396
TI  - Antioxidant effect of a fermented powder of Lady Joy bean in primary rat
      hepatocytes.
AB  - The role and beneficial effects of plant and food extracts against various
      diseases induced by oxidative stress have received much attention in recent
      years. Legumes are rich in bioactive compounds, and some studies suggest a
      correlation between their consumption and a reduced incidence of diseases.
      Primary cultures of rat hepatocytes were used to investigate whether and how an
      extract obtained from a fermented powder of bean named Lady Joy (Phaseolus
      vulgaris L.) is able to regulate antioxidant and detoxifying enzymes through the
      NRF2 pathway, inhibit NF-kB activation, and reduce H2O2-induced endoplasmic
      reticulum (ER) stress. All of the antioxidant and detoxifying enzymes studied
      were significantly up-regulated by Lady Joy treatment. Western blot showed that
      Nrf2 was activated by Lady Joy treatment. Also, cells treated with this fermented
      bean were partially protected against NF-kB activation resulting from H2O2
      stress. As a link between oxidative stress and ER dysfunction is hypothesized, we
      verified whether Lady Joy was able to protect cells from H2O2-induced ER stress,
      by studying the response of the proteins CHOP, BiP and caspase 12. The results of
      this study show that Lady Joy can induce the Nrf2 pathway, inhibit NF-kB, and
      protect ER from stress induced by H2O2. 

PMID- 26204397
TI  - Oncogene-dependent survival of highly transformed cancer cells under conditions
      of extreme centrifugal force - implications for studies on extracellular
      vesicles.
AB  - Extracellular vesicles (EVs), including exosomes, are a subject of intense
      interest due to their emission by cancer cells and role in intercellular
      communication. Earlier reports suggested that oncogenes, such as RAS, MET or
      EGFR, drive cellular vesiculation. Interestingly, these oncogenes may also
      traffic between cells using the EV-mediated emission and uptake processes. One of
      the main tools in the analysis of EVs are ultracentrifugation protocols designed
      to efficiently separate parental cells from vesicles through a sequence of steps
      involving increasing g-force. Here we report that ultracentrifugationonly EV
      preparations from highly transformed cancer cells, driven by the overexpression
      of oncogenic H-ras (RAS-3) and v-src (SRC-3), may contain clonogenic cancer
      cells, while preparations of normal or less aggressive human cell lines are
      generally free from such contamination. Introduction of a filtration step
      eliminates clonogenic cells from the ultracentrifugate. The survival of RAS-3 and
      SRC-3 cells under extreme conditions of centrifugal force (110,000 g) is oncogene
      induced, as EV preparations of their parental non-tumourigenic cell line (IEC-18)
      contain negligible numbers of clonogenic cells. Moreover, treatment of SRC-3
      cells with the SRC inhibitor (PP2) markedly reduces the presence of such cells in
      the unfiltered ultracentrifugate. These observations enforce the notion that EV
      preparations require careful filtration steps, especially in the case of material
      produced by highly transformed cancer cell types. We also suggest that oncogenic
      transformation may render cells unexpectedly resistant to extreme physical
      forces, which may affect their biological properties in vivo. 

PMID- 26204398
TI  - Changes in cell death of peripheral blood lymphocytes isolated from children with
      acute lymphoblastic leukemia upon stimulation with 7 Hz, 30 mT pulsed
      electromagnetic field.
AB  - Pulsed electromagnetic field (PEMF) influenced the viability of proliferating in
      vitro peripheral blood mononuclear cells (PBMCs) isolated from Crohn's disease
      patients as well as acute myeloblastic leukemia (AML) patients by induction of
      cell death, but did not cause any vital changes in cells from healthy donors.
      Experiments with lymphoid U937 and monocytic MonoMac6 cell lines have shown a
      protective effect of PEMF on the death process in cells treated with death
      inducers. The aim of the current study was to investigate the influence of PEMF
      on native proliferating leukocytes originating from newly diagnosed acute
      lymphoblastic leukemia (ALL) patients. The effects of exposure to PEMF were
      studied in PBMCs from 20 children with ALL. PBMCs were stimulated with three
      doses of PEMF (7 Hz, 30 mT) for 4 h each with 24 h intervals. After the last
      stimulation, the cells were double stained with annexin V and propidium iodide
      dye to estimate viability by flow cytometric analysis. The results indicated an
      increase of annexin V positive as well as double stained annexin V and propidium
      iodide positive cells after exposure to threefold PEMF stimulation. A low
      frequency pulsed electromagnetic field induces cell death in native proliferating
      cells isolated from ALL patients. The increased vulnerability of proliferating
      PBMCs to PEMF-induced interactions may be potentially applied in the therapy of
      ALL. The analysis of expression of apoptosis-related genes revealed changes in
      mRNA of some genes engaged in the intrinsic apoptotic pathway belonging to the
      Bcl-2 family and the pathway with apoptosis-inducing factor (AIF) abundance upon
      PEMF stimulation of PBMCs.

PMID- 26204399
TI  - Flow cytometric analysis of apoptosis in cryoconserved chicken primordial germ
      cells.
AB  - Our research aimed to compare the effects of four cryoprotectants and four slow
      freezing programs on the viability and apoptosis of primordial germ cells (PGCs)
      in vitro. PGCs were collected from chicken embryonic blood at Hamburger and
      Hamilton (HH) stages 14-16 and purified by Percoll density gradient
      centrifugation and then subjected to cryopreservation. We applied microscopy to
      determine the survival of PGCs after trypan blue staining and flow cytometry to
      examine apoptosis and viability after annexin V kit staining. We also examined
      the functionality of cryopreserved PGCs in vivo. Significant differences in
      viability of PGCs determined via microscopy and flow cytometry were observed. The
      most unfavorable combination for slow freezing PGCs was program 3 and MIX H (10%
      DMSO and 5% glycerol in Hank's solution supplemented with 10% FBS) as the
      cryoprotectant (48.43 and 15.37% live and early apoptotic PGCs, respectively).
      The highest average percentage of live PGCs (93.1%) and the lowest percentage of
      early apoptotic PGCs (6.5%) were achieved by slow freezing PGCs in the presence
      of DMSO F (10% DMSO in FBS) via program 1. Therefore, this method was chosen for
      the in vivo test. Cryopreserved (group 1) and freshly isolated (group 2) PGCs
      were transfectedwith a pEGFP-N1 plasmid, cultured under antibiotic selection, and
      then injected into 3-day-old embryos. After 5 days of incubation, we identified
      the EGFP marker gene in the gonads of 40 and 45% of recipients in groups 1 and 2,
      respectively. This is the first study to apply flow cytometry to examine the
      apoptosis and viability of cryopreserved PGCs. The in vitro and in vivo findings
      showed that the developed PGC cryoconservation method, depending on slow freezing
      at the rate of 2 degrees C/min (program 1) in the presence of 10% DMSO F, is an
      improvement over previous cryoconservation methods and may be a useful tool for
      the ex situ strategy of poultry biodiversity preservation. 

PMID- 26204400
TI  - Generation of an efficient artificial promoter of bovine skeletal muscle alpha
      actin gene (ACTA1) through addition of cis-acting element.
AB  - The promoter of skeletal muscle alpha-actin gene (ACTA1) is highly muscle
      specific. The core of the bovine ACTA1 promoter extends from +29 to -233, about
      262 base pairs (bp), which is sufficient to activate transcription in bovine
      muscle satellite cells. In this study, analysis by PCR site-specific mutagenesis
      showed that the cis-acting element SRE (serum response element binding factor)
      was processed as a transcriptional activator. In order to enhance the bovine
      ACTA1 promoter's activity, we used a strategy to modify it. We cloned a fragment
      containing three SREs from the promoter of ACTA1, and then one or two clones were
      linked upstream of the core promoter (262 bp) of ACTA1. One and two clones
      increased the activity of the ACTA1 promoter 3-fold and 10-fold, respectively,
      and maintained muscle tissue specificity. The modified promoter with two clones
      could increase the level of ACTA1 mRNA and protein 4-fold and 1.1-fold,
      respectively. Immunofluorescence results showed that green fluorescence of ACTA1
      increased. Additionally, the number of total muscle microfilaments increased.
      These genetically engineered promoters might be useful for regulating gene
      expression in muscle cells and improving muscle mass in livestock. 

PMID- 26204401
TI  - Biochemical evidence for Ca2+-independent functional activation of hPLSCR1 at low
      pH.
AB  - Human phospholipid scramblase 1 (hPLSCR1) is a Ca2+-dependent protein known to
      scramble phospholipids in the plasma membrane resulting in loss of membrane
      asymmetry. It has been reported that hPLSCR1 exhibits Ca2+- independent activity
      at low pH. However, the conformational changes induced at low pH leading to
      functional activation are not known. Our results showed that recombinant hPLSCR1
      was functionally activated at low pH, which is similar to the behavior of
      natively extracted hPLSCR1. Tryptophan fluorescence measurements showed a
      decrease in Ca2+-binding affinity at low pH, although not at pH 5.5. Far and near
      UV-CD revealed that low pH induced structural changes, with a significant
      increase in the beta-sheet content of the protein. At the physiological level,
      decreased hPLSCR1 expression was observed after a period of exposure to low pH.
      The effect occurred at the promoter level. The expression levels of hPLSCR1
      directly correlated with the sensitivity of HEK293 to apoptosis. Based on these
      results, we conclude that the mechanisms of Ca2+- and pH-induced functional
      activation of hPLSCR1 are different and that hPLSCR1 expression regulated by low
      pH could provide insights into the role of hPLSCR1 in cancer progression. 

PMID- 26204402
TI  - Catabolism of chondroitin sulfate.
AB  - Chondroitin sulfate (CS) is a ubiquitous component of the cell surface and
      extracellular matrix of animal tissues. CS chains are covalently bound to a core
      protein to form a proteoglycan, which is involved in various biological events
      including cell proliferation, migration, and invasion. Their functions are
      executed by regulating the activity of bioactive proteins, such as growth
      factors, morphogens, and cytokines. This review article focuses on the catabolism
      of CS. This catabolism predominantly occurs in lysosomes to control the activity
      of CS-proteoglycans. CS chains are fragmented by endo-type glycosidase(s), and
      the resulting oligosaccharides are then cleaved into monosaccharide moieties from
      the nonreducing end by exoglycosidases and sulfatases. However, the endo-type
      glycosidase responsible for the systemic catabolism of CS has not yet been
      identified. Based on recent advances in studies on hyaluronidases, which were
      previously considered to be hyaluronan-degrading enzymes, it appears that they
      recognize CS as their original substrate rather than hyaluronan and acquired
      hyaluronan-hydrolyzing activity at a relatively late stage of evolution. 

PMID- 26204403
TI  - The effect of hypoxia on PGE2-stimulated cAMP generation in HMEC-1.
AB  - Prostaglandin E2 (PGE2) is generated in various cells, including endothelial
      cells, and is responsible for various functions, such as vascular relaxation and
      angiogenesis. Effects of PGE2 are mediated via receptors EP1-EP4, among which EP2
      and EP4 are coupled to Gs protein which activates adenylate cyclase (AC) and cAMP
      synthesis. The aim of this work was to study the ability of human microvascular
      endothelial cells (HMEC-1) to synthesize cAMP in the presence of PGE2, and to
      determine the effect of hypoxia on the PGE2- stimulated cAMP level. It was
      decided to evaluate the effect of PGE2 on the secretion of VEGF, an inducer of
      angiogenesis. In summary, our findings show that PGE2 induces cAMP production,
      but hypoxia may impair PGE2-stimulated activity of the AC-cAMP signaling pathway.
      These results suggest that the cardioprotective effect of PGE2/EP4/cAMP may be
      attenuated during ischemia. Furthermore, this study indicates that the pro
      angiogenic effect of PGE2 is not associated with VEGF secretion in HMEC-1 cells. 

PMID- 26204404
TI  - Is there a connection between inflammation, telomerase activity and the
      transcriptional status of telomerase reverse transcriptase in renal failure?
AB  - Telomerase is involved in the elongation of telomeres. It remains active in very
      few types of cell in mature organisms. One such cell type is the lymphocytes. In
      this study, we investigated the activity and expression of telomerase in
      lymphocytes from renal failure patients and compared it to that for normal
      controls. Inflammation status was determined at the same time. The enzyme
      activity was measured using PCR-ELISA with peripheral blood mononuclear cells
      (PBMCs) from three groups: 53 healthy individuals, 50 patients with chronic
      kidney disease (CKD) and 50 dialysis patients. In the same cell populations, the
      expression of the reverse transcriptase of the human telomerase gene (hTERT) was
      measured via real-time PCR. The inflammationstatus of these individuals was
      determined by calculating the interleukin 6 (IL-6), IL-10, C-reactive protein
      (CRP) and tumor necrosis factor alpha (TNF-a) serum concentrations via ELISA. The
      lowest levels of telomerase activity were detected in CKD, and this group had the
      highest IL-6 and CRP values and the lowest hTERT expression. The dialysis group
      showed significant differences in comparison to the normal subjects and to the
      CKD patients. Further studies are warranted in order to explore the way
      inflammation influences telomerase activity and hTERT expression. 

PMID- 26204405
TI  - The beta-actin gene promoter of rohu carp (Labeo rohita) drives reporter gene
      expressions in transgenic rohu and various cell lines, including spermatogonial
      stem cells.
AB  - We previously characterized the beta-actin gene promoter of Indian domesticated
      rohu carp (Labeo rohita) and made a reporter construct via fusion to green
      fluorescence protein (GFP) cDNA. In this study, the same construct was used to
      breed transgenic rohu fish. About 20% of the transgenic offspring showed
      ubiquitous expression of the reporter GFP gene. In a few of the transgenic fish,
      we documented massive epithelial and/or muscular expression with visible green
      color under normal light. The expression of GFP mRNA was higher in the muscle
      tissue of transgenic fish than in that of non-transgenic fish. A highly efficient
      nucleofection protocol was optimized to transfect proliferating spermatogonial
      cells of rohu using this reporter construct. The beta-actin promoter also drove
      expressions in HEK293 (derived from human embryonic kidney cells), K562 (human
      leukemic cells) and SF21 (insect ovarian cells) lines. These findings imply
      conserved regulatory mechanisms of beta-actin gene expression across eukaryotes.
      Furthermore, the isolated beta-actin promoter with consensus regulatory elements
      has the potential to be used in generating transgenic carp with genes of interest
      and in basic biology research. 

PMID- 26204406
TI  - Molecular machines - a new dimension of biological sciences.
AB  - Biological systems are characterized by directional and precisely controlled flow
      of matter and information along with the maintenance of their structural
      patterns. This is possible thanks to sequential transformations of information,
      energy and structure carried out by molecular machines. The new perception of
      biological systems, including their mechanical aspects, requires the
      implementation of tools and approaches previously developed for engineering
      sciences. In this review paper, a biological system is presented in a new
      perspective as an ensemble of coordinated molecular devices functioning in the
      limited space confined by the biological membrane. The working of a molecular
      machine is presented using the example of F0F1 ATPase, and the general conditions
      necessary for the coordination of a large number of functional units are
      described. 

PMID- 26204407
TI  - Therapeutic potential of PACAP for neurodegenerative diseases.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is widely expressed in
      the central and peripheral nervous system. PACAP can initiate multiple signaling
      pathways through binding with three class B G-protein coupled receptors, PAC1,
      VPAC1 and VPAC2. Previous studies have revealed numerous biological activities of
      PACAP in the nervous system. PACAP acts as a neurotransmitter, neuromodulator and
      neurotrophic factor. Recently, its neuroprotective potential has been
      demonstrated in numerous in vitro and in vivo studies. Furthermore, evidence
      suggests that PACAP might move across the blood-brain barrier in amounts
      sufficient to affect the brain functions. Therefore, PACAP has been examined as a
      potential therapeutic method for neurodegenerative diseases. The present review
      summarizes the recent findings with special focus on the models of Alzheimer's
      disease (AD) and Parkinson's disease (PD). Based on these observations, the
      administered PACAP inhibits pathological processes in models of AD and PD, and
      alleviates clinical symptoms. It thus offers a novel therapeutic approach for the
      treatment of AD and PD. 

PMID- 26204408
TI  - A newly isolated yeast as an expression host for recombinant lipase.
AB  - Pichia guilliermondii strain SO isolated from spoiled orange was developed for
      use as an alternative expression host by using Pichia pastoris as the model of
      the experiment. This is the first study to report on the capability of P.
      guilliermondii SO as a host to express thermostable T1 lipase from Geobacillus
      zalihae. Alcohol oxidase and formaldehyde dehydrogenase promoters were present in
      the yeast genome. Interestingly, the recombinant yeast [SO/pPICZalphaB/T1-2
      (SO2)] took only 30 h to reach optimal production with minimal methanol induction
      [1.5% (v/v)] in YPTM medium, as compared to P. pastoris, which took longer to
      reach its optimal condition. The purification yield of the His-tagged fusion
      lipase was 68.58%, with specific activity of 194.58 U/mg. The optimum temperature
      was 65 degrees C at pH 9 in glycine-NaOH buffer, and it was stable up to 70
      degrees C in a wide pH range from pH 5 to 12. In conclusion, a newly isolated
      yeast from spoiled orange has been proven suitable for use as an expression host.

PMID- 26204409
TI  - Identification of shorter length lamin A protein in mouse ear cartilage tissue.
AB  - Lamin A is an intermediate filament protein which is cleaved by the enzyme, FACE
      1 at VTRSY?L. The cleavage is the final step in the production of the mature
      lamin A protein. The mature lamin A protein localizes in the inner membrane of
      the nucleus. The mutation in the lamin A gene causes many diseases, including
      accelerated aging. It is known that the protein is not expressed in neuronal
      cells of the brain. Many splicing variants of the lamin A gene have been
      reported. In this study, the amino acid sequence VTRSY (a penta-peptide repeat)
      was found in three different sites of the C-terminal end of the lamin A protein,
      the protein expressed in cells of ear cartilage tissues is shorter than the
      protein expressed in cells of the skin tissues. Using two lamin A antibodies, it
      was found that the amino acid sequence between penta-peptide 2 and 3 is missing
      in lamin A protein that was expressed in the cells of mouse ear cartilage tissue,
      besides the RT-PCR data confirmed that the corresponding coding sequence between
      the penta repeat 2 and 3 is intact. Cleavage may occur at the penta-peptide
      (VTRSY) at site 3 in the lamin A tail of mouse ear cartilage. 

PMID- 26204410
TI  - Relationship among IL-6, LDL cholesterol and lipid peroxidation.
AB  - Previous studies evidenced a significant reduction in serum cholesterol levels
      during an episode of acute inflammation. The aim of the present study was to
      verify the hypothesis of a regulatory role of cytokines through an in vitro model
      that simulates a situation of vascular inflammation and high levels of LDL or
      lipoperoxides. Human microvascular endothelial cells-1 were used in all
      experiments. The cells were exposed for 24 h to increasing doses of LDL, oxidized
      lipoprotein, and 8-isoprostane (in the absence or presence of SQ29.548, a TXA2
      receptor antagonist). Moreover, LDL receptor and oxidized lipoprotein receptor
      expression analyzed after endothelial cells' incubation with increasing doses of
      interleukin-6. The ELISA test and quantitative real-time PCR were performed.
      Endothelial cells showed a significant increase in interleukin-6 medium levels
      associated with LDL, oxidized LDL and with the degree of oxidation (absence or
      presence of SQ29.548), while 8-isoprostane did not. Treatment of human
      microvascular endothelial cells-1 for 24 h with increasing doses of interleukin-6
      significantly enhanced LDL receptor and oxidized lipoprotein receptor-1 mRNA
      expression. Our data suggest the presence of a compensatory mechanism. The
      induction of a significant increase of IL-6 does not seem to be caused by the
      presence of the biological activity of 8-isoprostane. 

PMID- 26204411
TI  - Study strategies for long non-coding RNAs and their roles in regulating gene
      expression.
AB  - Long non-coding RNAs (lncRNAs) have attracted considerable attention recently due
      to their involvement in numerous key cellular processes and in the development of
      various disorders. New high-throughput methods enable their study on a genome
      wide scale. Numerous lncRNAs have been identified and characterized as important
      members of the biological regulatory network, with significant roles in
      regulating gene expression at the epigenetic, transcriptional and post
      transcriptional levels. This paper summarizes the diverse mechanisms of action of
      these lncRNAs and looks at the study strategies in this field. A major challenge
      in future study is to establish more effective bioinformatics and experimental
      methods to explore the functions, detailed mechanisms of action and structures
      deciding the functional diversity of lncRNAs, since the vast majority remain
      unresolved. 

PMID- 26204416
TI  - Feasibility of a Sexual Health Clinic Within Cancer Care: A Pilot Study Using
      Qualitative Methods.
AB  - BACKGROUND: As cancer survival rates increase, so does the imperative for a
      satisfying quality of life, including a fulfilling sexual life. OBJECTIVE: The
      feasibility and effectiveness of a newly formed Sexual Health Clinic were
      determined using a nurse-led format, which provided support to survivors in a
      cancer care setting. METHODS: Twenty-one cancer survivors received assessment,
      education, and tailored sexual health support by an oncology nurse with
      specialized skills in sexual health. Two months later, semistructured interviews
      focused on patients' personal experiences. Questionnaires were also administered
      to healthcare providers involved in providing the follow-up care. RESULTS:
      Participants presented with sexual concerns that were psychological, physical,
      and/or relational. Scores on validated measures of sexual functioning were in the
      range comparable to those with a sexual dysfunction. Participants were open to
      being asked about sexual health and wanted professionals available who were
      skilled in dealing with sexual health services. Most participants experienced an
      improvement in their well-being and/or sexual life following participation. Some
      noted more confidence when speaking with their partner about sexual concerns.
      CONCLUSION: Our pilot Sexual Health Clinic was feasible, and evidence for its
      effectiveness was based on qualitative feedback. Participants and providers
      identified a strong need for the inclusion of sexual health services in cancer
      care. IMPLICATIONS FOR PRACTICE: Oncology nurses are in a key position to
      initiate discussions surrounding sexual health issues related to cancer
      treatment. Self-awareness, sensitivity, and a nonjudgmental approach are required
      to address this dimension of holistic cancer care.

PMID- 26204415
TI  - Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly
      Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin.
AB  - Skin is an easily accessible organ, and therapeutic gene transfer to skin remains
      an attractive alternative for the treatment of skin diseases. Although we have
      previously documented potent lentiviral gene delivery to human skin, vectors
      based on adeno-associated virus (AAV) rank among the most promising gene delivery
      tools for in vivo purposes. Thus, we compared the potential usefulness of various
      serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to
      human skin in a xenotransplanted mouse model. Vector constructs encoding firefly
      luciferase were packaged in AAV capsids of serotype 1, 2, 5, 6, 8, and 9 and
      separately administered by intradermal injection in human skin transplants. For
      all serotypes, live bioimaging demonstrated low levels of transgene expression in
      the human skin graft, and firefly luciferase expression was observed primarily in
      neighboring tissue outside of the graft. In contrast, gene delivery by
      intradermally injected lentiviral vectors was efficient and led to extensive and
      persistent firefly luciferase expression within the human skin graft only. The
      study demonstrates the limited capacity of single-stranded AAV vectors of six
      commonly used serotypes for gene delivery to human skin in vivo. 

PMID- 26204417
TI  - Psychometric Properties of the Breast Cancer Screening Beliefs Questionnaire
      Among Women of Indian Ethnicity Living in Australia.
AB  - BACKGROUND: Indian women have been consistently reported as having low
      participation in breast cancer screening practices. A valid and reliable
      instrument to explore their breast cancer beliefs is essential for development of
      interventions to promote breast cancer screening practices. OBJECTIVE: The aim of
      this study was to report the psychometric properties of the Breast Cancer
      Screening Beliefs Questionnaire (BCSBQ) in an Indian community in Australia.
      METHODS: A convenience sample of 242 Indian Australian women was recruited from
      Indian community organizations and personal networking. Explanatory factor
      analysis was conducted to study the factor structure. Clinical validity was
      examined by Cuzick's nonparametric test, and Cronbach's alpha was used to assess
      internal consistency reliability. RESULTS: Exploratory factor analysis showed a
      similar fit to the hypothesized 3-factor structure. The frequency of breast
      cancer screening practices was significantly associated with attitudes toward
      general health check-up. Knowledge and perceptions about the breast cancer scale
      were not significantly associated with clinical breast examinations and
      mammography. Perceived barriers to mammography were much less evident among women
      who engaged in breast awareness and clinical breast examination. Results
      indicated that the BCSBQ had satisfactory validity and internal consistency.
      Cronbach's alpha of the 3 subscales ranged from .81 to .91. CONCLUSIONS: The
      BCSBQ is a culturally appropriate, valid, and reliable instrument for assessing
      the beliefs, knowledge, and attitudes about breast cancer and breast cancer
      screening practices among women of Indian ethnic extraction living in Australia.
      IMPLICATION FOR PRACTICE: The BCSBQ can be used to provide nurses with
      information relevant for the development of culturally sensitive breast health
      education programs.

PMID- 26204418
TI  - Ultrasound/Laparoscopic Camera-Guided Transversus Abdominis Plane Block for Renal
      Transplant Donors: A Randomized Controlled Trial.
AB  - BACKGROUND: The most common treatment modality for postoperative pain relief
      following laparoscopic surgery is multimodal, using nonsteroidal antiinflammatory
      drugs (NSAID), opioids, and infiltration of local anesthetics. Because NSAIDs are
      nephrotoxic, local infiltration does not relieve deep tissue pain, and opioids
      have an adverse effects profile including pruritus, nausea, vomiting,
      oversedation, apnea, and decreased gastrointestinal motility. Therefore, the use
      of a regional analgesic technique can lead to an improved quality of recovery.
      The aim of this prospective, randomized, placebo-controlled study was to evaluate
      the effect of TAP block on postoperative verbal analog scale (VAS) scores and
      total morphine requirements in the first 24 hours after laparoscopic live donor
      nephrectomy. MATERIAL AND METHODS: After obtaining approval from the hospital
      ethics committee and written informed consent from the patients, 49 ASA I-II
      patients undergoing laparoscopic donor nephrectomy, aged 18 years or over, were
      included in this prospective, randomized, controlled study. In this clinical
      trial patients were divided into 2 groups: TAP block group (group T) and placebo
      group (group P). The demographic variables, pain scores, morphine consumption,
      level of sedation, presence of postoperative nausea, vomiting, pruritus, and
      average length of postoperative stay were reviewed. RESULTS: The pain scores were
      significantly lower after TAP block with bupivacaine at most but not all time
      points. Patients receiving the TAP block with bupivacaine required less morphine
      up to 24 hours after surgery compared with the saline group. CONCLUSIONS: USG
      guided TAP block as part of a balanced analgesia regimen is of benefit in
      reducing postoperative pain and morphine consumption after laparoscopic donor
      nephrectomy.

PMID- 26204419
TI  - Biotin-Containing Reduced Graphene Oxide-Based Nanosystem as a Multieffect
      Anticancer Agent: Combining Hyperthermia with Targeted Chemotherapy.
AB  - Among the relevant properties of graphene derivatives, their ability of acting as
      an energy-converting device so as to produce heat (i.e., thermoablation and
      hyperthermia) was more recently taken into account for the treatment of solid
      tumors. In this pioneering study, for the first time, the in vitro RGO-induced
      hyperthermia was assessed and combined with the stimuli-sensitive anticancer
      effect of a biotinylated inulin-doxorubicin conjugate (CJ-PEGBT), hence, getting
      to a nanosystem endowed with synergic anticancer effects and high specificity. CJ
      PEGBT was synthesized by linking pentynoic acid and citraconic acid to inulin.
      The citraconylamide pendants, used as pH reversible spacer, were exploited to
      further conjugate doxorubicin, whereas the alkyne moiety was orthogonally
      functionalized with an azido PEG-biotin derivative by copper(II) catalyzed 1,3
      dipolar cycloaddition. DSC measures, AFM, and UV spectrophotometry were employed
      to systematically investigate adsorption of CJ-PEGBT onto RGO and its
      physicochemical stability in aqueous media, demonstrating that a stable pi-staked
      nanosystem can be obtained. In vitro tests using cancer breast cells (MCF-7)
      showed the ability of the RGO/CJ-PEGBT of efficiently killing cancer cells both
      via a selective laser beam thermoablation and hyperthermia-triggered
      chemotherapy. If compared with the nonbiotinylated nanosystem, including virgin
      RGO and the free conjugate, RGO/CJ-PEGBT is endowed with a smart combination of
      properties which warrant potential as an anticancer nanomedicine. 

PMID- 26204420
TI  - Identifying the sources of nitrate contamination of groundwater in an
      agricultural area (Haean basin, Korea) using isotope and microbial community
      analyses.
AB  - An integrated study based on hydrogeochemical, microbiological and dual isotopic
      approaches for nitrate and sulfate was conducted to elucidate sources and
      biogeochemical reactions governing groundwater contaminants in different seasons
      and under different land use in a basin of Korea. The land use in the study area
      is comprised of forests (58.0%), vegetable fields (27.6%), rice paddy fields
      (11.4%) and others (3.0%). The concentrations of NO3-N and SO4(2-) in groundwater
      in vegetable fields were highest with 4.2-15.2 mg L(-1) and 1.6-19.7 mg L(-1)
      respectively, whereas under paddy fields NO3-N concentrations ranged from 0 to
      10.7 mg L(-1) and sulfate concentrations were ~15 mg L(-1). Groundwater with high
      NO3-N concentrations of >10mgL(-1) had delta(15)N-NO3(-) values ranging from 5.2
      to 5.90/00 and delta(18)O values of nitrate between 2.7 and 4.60/00 suggesting
      that the nitrate was mineralized from soil organic matter that was amended by
      fertilizer additions. Elevated concentrations of SO4(2-) with delta(34)S-SO4(2-)
      values between 1 and 60/00 in aquifers in vegetable fields indicated that a
      mixture of sulfate from atmospheric deposition, mineralization of soil organic
      matter and from synthetic fertilizers is the source of groundwater sulfate.
      Elevated delta(18)O-NO3(-) and delta(18)O-SO4(2-) values in samples collected
      from the paddy fields indicated that denitrification and bacterial sulfate
      reduction are actively occurring removing sulfate and nitrate from the
      groundwater. This was supported by high occurrences of denitrifying and sulfate
      reducing bacteria in groundwater of the paddy fields as evidenced by 16S rRNA
      pyrosequencing analysis. This study shows that dual isotope techniques combined
      with microbial data can be a powerful tool for identification of sources and
      microbial processes affecting NO3(-) and SO4(2-) in groundwater in areas with
      intensive agricultural land use.

PMID- 26204421
TI  - Scope of practice: a statement of the American College of Medical Genetics and
      Genomics (ACMG).
AB  - DISCLAIMER: These recommendations are designed primarily as an educational
      resource for medical geneticists and other healthcare providers to help them
      provide quality medical genetics services. Adherence to these recommendations
      does not necessarily ensure a successful medical outcome. These recommendations
      should not be considered inclusive of all proper procedures and tests or
      exclusive of other procedures and tests that are reasonably directed to obtaining
      the same results. In determining the propriety of any specific procedure or test,
      geneticists and other clinicians should apply their own professional judgment to
      the specific clinical circumstances presented by the individual patient or
      specimen. It may be prudent, however, to document in the patient's record the
      rationale for any significant deviation from these recommendations.Genet Med 17
      9.

PMID- 26204422
TI  - American College of Medical Genetics and Genomics: revised scope of practice and
      strategic plan.

PMID- 26204423
TI  - The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102
      individuals and recommendations for care.
AB  - PURPOSE: Cockayne syndrome (CS) is a rare, autosomal-recessive disorder
      characterized by microcephaly, impaired postnatal growth, and premature
      pathological aging. It has historically been considered a DNA repair disorder;
      fibroblasts from classic patients often exhibit impaired transcription-coupled
      nucleotide excision repair. Previous studies have largely been restricted to case
      reports and small series, and no guidelines for care have been established.
      METHODS: One hundred two study participants were identified through a network of
      collaborating clinicians and the Amy and Friends CS support groups. Families with
      a diagnosis of CS could also self-recruit. Comprehensive clinical information for
      analysis was obtained directly from families and their clinicians. RESULTS AND
      CONCLUSION: We present the most complete evaluation of Cockayne syndrome to date,
      including detailed information on the prevalence and onset of clinical features,
      achievement of neurodevelopmental milestones, and patient management. We confirm
      that the most valuable prognostic factor in CS is the presence of early
      cataracts. Using this evidence, we have created simple guidelines for the care of
      individuals with CS. We aim to assist clinicians in the recognition, diagnosis,
      and management of this condition and to enable families to understand what
      problems they may encounter as CS progresses.Genet Med 18 5, 483-493.

PMID- 26204426
TI  - Binary Nickel-Cobalt Oxides Electrode Materials for High-Performance
      Supercapacitors: Influence of its Composition and Porous Nature.
AB  - Nickel-cobalt oxides were prepared by coprecipitation of their hydroxides
      precursors and a following thermal treatment under a moderate temperature. The
      preformed nickel-cobalt bimetallic hydroxide exhibited a flower-like morphology
      with single crystalline nature and composed of many interconnected nanosheets.
      The ratio of Ni to Co in the oxides could easily be controlled by adjusting the
      composition of the original reactants for the preparation of hydroxide
      precursors. It was found that both the molecular ratio of Ni to Co and the
      annealing temperature had significant effects on their porous structure and
      electrochemical properties. The effect of the Ni/Co ratio on the pseudocapacitive
      properties of the binary oxide was investigated in this work. The binary metal
      oxide with the exact molar ratio of Ni:Co = 0.8:1 annealed at 300  degrees C,
      showing an optimum specific capacitance of 750 F/g. However, too high an
      annealing temperature would lead to a large crystal size, a low specific surface
      area, as well as a much lower pore volume. With the use of the binary metal oxide
      with Ni:Co = 0.8:1 and activated carbon as the positive and negative electrode,
      respectively, the assembled hybrid capacitor could exhibit a high-energy density
      of 34.9 Wh/kg at the power density of 875 W/kg and long cycling life (86.4%
      retention of the initial value after 10000 cycles). 

PMID- 26204424
TI  - Effect of Chirality on Common in Vitro Experiments: An Enantiomeric Pair
      Analysis.
AB  - This analysis elucidates the impact of small molecule architecture on common in
      vitro ADME assays. In vitro parameters considered in this analysis included Caco
      2 permeability/efflux, CYP3A4 inhibition, hERG inhibition, and rat microsomal
      extraction ratio (ER). The statistical significance and practical meaningfulness
      of chirality were determined by comparison of the distribution of enantiomers
      with the experimental variation distribution observed from duplicate
      measurements. Statistical tools were applied to characterize the role of
      molecular architecture on the outcome of a given in vitro assay. We found that
      CYP3A4 inhibition, hERG inhibition, Caco-2 permeability, and efflux are unlikely
      to be modulated by chirality. However, rat microsomal ER provides a statistically
      significant, and quantitatively meaningful, chance of being influenced by
      chirality. 

PMID- 26204425
TI  - Photolytic Cross-Linking to Probe Protein-Protein and Protein-Matrix Interactions
      in Lyophilized Powders.
AB  - Protein structure and local environment in lyophilized formulations were probed
      using high-resolution solid-state photolytic cross-linking with mass
      spectrometric analysis (ssPC-MS). In order to characterize structure and
      microenvironment, protein-protein, protein-excipient, and protein-water
      interactions in lyophilized powders were identified. Myoglobin (Mb) was
      derivatized in solution with the heterobifunctional probe succinimidyl 4,4'
      azipentanoate (SDA) and the structural integrity of the labeled protein (Mb-SDA)
      confirmed using CD spectroscopy and liquid chromatography/mass spectrometry (LC
      MS). Mb-SDA was then formulated with and without excipients (raffinose, guanidine
      hydrochloride (Gdn HCl)) and lyophilized. The freeze-dried powder was irradiated
      with ultraviolet light at 365 nm for 30 min to produce cross-linked adducts that
      were analyzed at the intact protein level and after trypsin digestion. SDA
      labeling produced Mb carrying up to five labels, as detected by LC-MS. Following
      lyophilization and irradiation, cross-linked peptide-peptide, peptide-water, and
      peptide-raffinose adducts were detected. The exposure of Mb side chains to the
      matrix was quantified based on the number of different peptide-peptide, peptide
      water, and peptide-excipient adducts detected. In the absence of excipients,
      peptide-peptide adducts involving the CD, DE, and EF loops and helix H were
      common. In the raffinose formulation, peptide-peptide adducts were more
      distributed throughout the molecule. The Gdn HCl formulation showed more protein
      protein and protein-water adducts than the other formulations, consistent with
      protein unfolding and increased matrix interactions. The results demonstrate that
      ssPC-MS can be used to distinguish excipient effects and characterize the local
      protein environment in lyophilized formulations with high resolution. 

PMID- 26204429
TI  - Rotation/Torsion Coupling in H5(+), D5(+), H4D(+), and HD4(+) Using Diffusion
      Monte Carlo.
AB  - Two methods for studying the rotation/torsion coupling in H5(+) are described.
      The first involves a fixed-node treatment in which the nodal surfaces are
      obtained from a reduced dimensional calculation in which only the rotations of
      the outer H2 groups are considered. In the second, the torsion and rotation
      dependence of the wave function is described in state space, and the other
      internal coordinates are described in configuration space. Such treatments are
      necessary for molecules, like H5(+), where there is a very low-energy barrier to
      internal rotation. The results of the two approaches are found to be in good
      agreement with previously reported energies for J = 0. The diffusion Monte Carlo
      treatment allows us to extend the calculations to low J, and results are reported
      for the three lowest energy torsion excited states with J <= 3. For the level of
      rotational and vibrational excitation investigated, only modest changes in the
      vibrational wave functions are found. The effects of deuteration are also
      investigated, focusing on D5(+) and the symmetric variants of H4D(+) and HD4(+). 

PMID- 26204430
TI  - Supramolecular helical nanofibers assembled from a pyridinium-functionalized
      methyl glycyrrhetate amphiphile.
AB  - A glycyrrhetate-containing amphiphile, MGP (1-[2-(methyl glycyrrhetate)-2
      oxoethyl]pyridinium bromide), has been synthesized, and found to assemble into
      supramolecular helical nanofibers in chloroform/aromatic solvents, which are
      primarily driven by pi-pi stacking, van der Waals forces, and hydrophobic
      interactions. During the assembly process, MGP stacked into J-aggregates
      resulting in the sequestration of the hydrophilic pyridinium cation within the
      interior with the concomitant projection of its hydrophobic skeleton on the
      outside surface. Ultimately, this protrusion generated a staggered angle due to
      the steric hindrance between stacked molecules. This staggered angle further led
      to molecular misalignments and the formation of helical fibrils, which could
      twist with each other to fabricate larger helical fibers. Consequently, a gel was
      formed by intertwining these nanofibers into three-dimensional networks. Using
      this strategy, we found that other triterpenoid-tailored pyridinium amphiphiles
      are also potential scaffolds for supramolecular helical structures. This work
      provides a facile approach for the fabrication of supramolecular macroscopic
      chiral nanostructures that originate from natural products. 

PMID- 26204428
TI  - Measuring Compositions in Organic Depth Profiling: Results from a VAMAS
      Interlaboratory Study.
AB  - We report the results of a VAMAS (Versailles Project on Advanced Materials and
      Standards) interlaboratory study on the measurement of composition in organic
      depth profiling. Layered samples with known binary compositions of Irganox 1010
      and either Irganox 1098 or Fmoc-pentafluoro-l-phenylalanine in each layer were
      manufactured in a single batch and distributed to more than 20 participating
      laboratories. The samples were analyzed using argon cluster ion sputtering and
      either X-ray photoelectron spectroscopy (XPS) or time-of-flight secondary ion
      mass spectrometry (ToF-SIMS) to generate depth profiles. Participants were asked
      to estimate the volume fractions in two of the layers and were provided with the
      compositions of all other layers. Participants using XPS provided volume
      fractions within 0.03 of the nominal values. Participants using ToF-SIMS either
      made no attempt, or used various methods that gave results ranging in error from
      0.02 to over 0.10 in volume fraction, the latter representing a 50% relative
      error for a nominal volume fraction of 0.2. Error was predominantly caused by
      inadequacy in the ability to compensate for primary ion intensity variations and
      the matrix effect in SIMS. Matrix effects in these materials appear to be more
      pronounced as the number of atoms in both the primary analytical ion and the
      secondary ion increase. Using the participants' data we show that organic SIMS
      matrix effects can be measured and are remarkably consistent between instruments.
      We provide recommendations for identifying and compensating for matrix effects.
      Finally, we demonstrate, using a simple normalization method, that virtually all
      ToF-SIMS participants could have obtained estimates of volume fraction that were
      at least as accurate and consistent as XPS. 

PMID- 26204432
TI  - Crystal Structures of Al-Nd Codoped Zirconolite Derived from Glass Matrix and
      Powder Sintering.
AB  - Zirconolite is a candidate host for immobilizing long-lived radionuclides.
      Zirconolite-based glass-ceramics in the CaO-SiO2-Al2O3-TiO2-ZrO2-Nd2O3-Na2O
      matrix are a potential waste form for immobilizing actinide radionuclides and can
      offer double barriers to immobilize radioactive elements. However, the X-ray
      diffraction patterns of the zirconolite derived from the glass matrix (glass
      ceramic, GC) are significantly different from those prepared by powder sintering
      (PS). In this Article, the crystal structures of Al-Nd codoped zirconolite grown
      via the glass matrix route and the powder sintering route are investigated in
      detail. Two samples of Al-Nd codoped zirconolite were prepared: one was grown
      from a CaO-SiO2-Al2O3-TiO2-ZrO2-Nd2O3-Na2O glass matrix, and the other was
      prepared with a Ca0.75Nd0.25ZrTi1.75Al0.25O7 composition by powder sintering. The
      samples were then characterized using powder X-ray diffraction (PXRD), scanning
      electron microscopy (SEM), transmission electron microscopy-energy dispersive X
      ray spectroscopy (TEM-EDX), and selected area electron diffraction (SAED). The
      chemical composition of the 100-500 nm zirconolite crystals grown from a glass
      matrix was determined by TEM-EDX to be Ca0.83Nd0.25Zr0.85Ti1.95Al0.11O7. PXRD and
      SAED results showed that these two Al-Nd codoped zirconolite phases were
      crystallized in space group C12/c1. The HRTEM images and SAED results showed that
      there were heavy stacking faults in the zirconolite crystals grown from the glass
      matrix. In contrast, far fewer defects were found in the zirconolite crystals
      prepared by powder sintering. The split-atom model was adopted for the first time
      to construct the Al-Nd codoped zirconolite structure grown from glass during the
      Rietveld refinement. The isostructural method assisted by Rietveld refinement was
      used to resolve the Al-Nd codoped zirconolite structures prepared by different
      methods. The occupancies of the cation sites were identified, and the
      distribution behavior of Nd(3+) was further investigated. The results indicate
      that the heavy stacking faults may lead to substantial differences in the Al-Nd
      codoped zirconolite structures prepared by these two fabrication routes. 

PMID- 26204431
TI  - Delayed Fatal Hemorrhage Due to Small Bowel Mesenteric Laceration.
AB  - Injuries of small bowel and its mesentery due to blunt trauma are uncommon. Of
      deaths due to delayed intra-abdominal hemorrhage, mesenteric laceration is a rare
      cause of hemoperitoneum.A case of a 33-year-old man, who was hospitalized with
      chest and retroperitoneal trauma after a forklift rollover, is presented. He died
      10 days after the incident. At autopsy, he had a massive hemoperitoneum due to a
      small bowel mesenteric laceration, which was not diagnosed during his clinical
      course. Microscopic examination of the hematoma around the laceration revealed
      healing and ruptured pseudoaneurysms in the distal branches of the superior
      mesenteric artery. 

PMID- 26204435
TI  - Direct beta-C(sp(3))-H Functionalization of Aliphatic Amines to alpha,beta
      Unsaturated Imines, Aldehydes, and Chromenes.
AB  - A metal-free method for direct beta-C(sp(3))-H functionalization of aliphatic
      amine was developed. The method is based on a reaction that yields enamine
      directly from the corresponding aliphatic amine, which otherwise requires the aid
      of metallic reagent and/or external oxidant. The reaction is operationally
      simple, general, and highly efficient in functionalizing both cyclic and acyclic
      amines. Structurally diverse unsaturated imines were obtained from N
      heterocycles, while acyclic amines provided 2-alkyl cinnamaldehyde and benzopyran
      derivatives with excellent E/Z-selectivity. 

PMID- 26204436
TI  - Efficient visible driven photocatalyst, silver phosphate: performance,
      understanding and perspective.
AB  - Photocatalysis is a promising technology that can contribute to renewable energy
      production from water and water purification. In order to further develop the
      field and meet industrial requirements, it is imperative to focus on advancing
      high efficiency visible light photocatalysts, such as silver phosphate (Ag3PO4).
      This review aims to highlight the recent progress made in the field, focusing on
      oxygen production from water, and organic contaminant decomposition using Ag3PO4.
      The most important advances are discussed and explained in detail, including
      semiconductor-semiconductor junctions, metal-semiconductor junctions, exposing
      facet control, and fundamental understanding using advanced spectroscopies and
      computational chemistry. The review then concludes by critically summarising both
      findings and current perspectives, and ultimately how the field might best
      advance in the near future. 

PMID- 26204434
TI  - Atomic Level Distributed Strain within Graphene Divacancies from Bond Rotations.
AB  - Vacancy defects play an important role in influencing the properties of graphene,
      and understanding their detailed atomic structure is crucial for developing
      accurate models to predict their impact. Divacancies (DVs) are one of the most
      common defects in graphene and can take three different structural forms through
      various sequences of bond rotations to minimize the energy. Using aberration
      corrected transmission electron microscopy with monochromation of the electron
      source, we resolve the position of C atoms in graphene and measure the C-C bond
      lengths within the three DVs, enabling a map of bond strain to be generated. We
      show that bond rotations reduce the maximum single bond strain reached within a
      DV and help distribute the strain over a larger number of bonds to minimize the
      peak magnitude. 

PMID- 26204437
TI  - Coherent light-driven electron transport through polycyclic aromatic hydrocarbon:
      laser frequency, field intensity, and polarization angle dependence.
AB  - A laser field is a potential control tool for operating ultrafast electronic
      devices due to a wide variety of options such as field strength, frequency, and
      polarization. To investigate these variables upon electron transport through a
      single-molecule device, we simulate a phenyl-acetylene macrocycle (PAM) within a
      linear-polarized laser field using single-particle Green's functions combined
      with the non-Hermitian Floquet theory. In the absence of the laser field, the PAM
      behaves as a perfect insulator due to destructive quantum interference. In the
      weak-field regime, field-amplitude power laws for one-, two-, and three-photon
      assisted tunneling are evident in the computational results. The study reveals a
      range of experimentally feasible field strengths for the observation of
      picoampere current caused by photon assisted tunneling. In addition, we find that
      the light-driven current is proportional to the cosine square of the polarization
      angle, and molecular electronic structure is revealed by the current-frequency
      characteristics. The origin of these behaviors is established using non-Hermitian
      Floquet perturbation analysis. The computations show that PAM-based
      optoelectronic switches have robust large on-off switching ratios under weak
      field operating conditions, which are not sensitive to asymmetric molecule-lead
      couplings. 

PMID- 26204427
TI  - Atropo- and Diastereoselective Construction of Tetracyclic Biphenylazepinium
      Salts Derived from Aminoalcohols: Use as Catalysts in Enantioselective Asymmetric
      Epoxidation.
AB  - A range of new biphenylazepinium salt organocatalysts effective for asymmetric
      epoxidation has been developed incorporating an additional substituted
      oxazolidine ring, and providing improved enantiocontrol in alkene epoxidation
      over the parent structure. Starting from enantiomerically pure aminoalcohols,
      tetracyclic iminium salts were obtained as single diastereoisomers through an
      atroposelective oxazolidine formation. 

PMID- 26204433
TI  - Differential Nanosecond Protein Dynamics in Homologous Calcium Sensors.
AB  - Shaping the temporal response of photoreceptors is facilitated by a well-balanced
      second messenger cascade, in which two neuronal Ca(2+)-sensor proteins operate in
      a sequential relay mechanism. Although they share structurally similar sensing
      units, they differentially activate the same target protein. Here, as a
      prototypical case in Ca(2+)-mediated signal processing, we investigate
      differential cellular responsiveness in protein conformational dynamics on a
      nanosecond time scale. For this, we have site-specifically labeled cysteine
      residues in guanylate cyclase-activating protein GCAP1 by the fluorescent dye
      Alexa647 and probed its local environment via time-resolved fluorescence
      spectroscopy. Fluorescence lifetime and rotational anisotropy measurements reveal
      a distinct structural movement of the polypeptide chain around position 106 upon
      release of Ca(2+). This is supported by analyzing the diffusional dye motion in a
      wobbling-in-a-cone model and by molecular dynamics simulations. We conclude that
      GCAP1 and its cellular cognate GCAP2 operate by distinctly different switching
      mechanisms despite their high structural homology. 

PMID- 26204438
TI  - Molecular tectonics: heterometallic coordination networks based on a Pt(II)
      organometallic metallatecton.
AB  - Combinations of a neutral organometallic tecton based on a square planar Pt(ii)
      complex bearing two triphenylphosphine groups and two 4-ethynylpyridyl
      coordinating moieties in trans positions, with various metal halides (MX2, M =
      Co(ii), Ni(ii), Cd(ii), X = Cl(-) or Br(-)) lead to the formation of 2D grid type
      heterobimetallic coordination networks in the crystalline phase. 

PMID- 26204439
TI  - Comparison of Health State Utility Measures in Patients With Head and Neck
      Cancer.
AB  - IMPORTANCE: Accurate measurement of health state utilities (HU) is the
      cornerstone for cost-utility analyses and the valuation of quality of life for
      given health states. Current indirect methods of HU derivation lack face validity
      for patients with head and neck cancer. The appropriateness of these measures
      compared with direct methods, such as the standard gamble (SG), time trade-off
      (TTO), and visual analog scale (VAS), have not been assessed in this patient
      population. OBJECTIVE: To assess the convergent and construct validities of 5
      different HU derivation methods in patients with head and neck cancer. DESIGN,
      SETTING, AND PARTICIPANTS: In a cross-sectional study, we recruited 100
      consecutive patients with squamous cell carcinoma of the upper aerodigestive
      tract treated in the outpatient surgical oncology clinics of the Princess
      Margaret Cancer Centre from August 1 through October 31, 2014. We enrolled
      patients with a minimum of 3 months of follow-up after completion of treatment
      and no evidence of recurrent or metastatic disease. Participants completed SG,
      TTO, and VAS exercises, the EuroQoL instrument (EQ-5D), and the Health Utilities
      Index Mark 3 (HUI3) questionnaire. Data analysis was performed November 1 through
      December 15, 2014. EXPOSURES: Head and neck cancer and HU measures. MAIN OUTCOMES
      AND MEASURES: We assessed convergent validity of the 5 HU instruments through
      Spearman rank order correlation assessment. We determined construct validity
      through a priori hypotheses relating HU scores with clinical indexes of disease
      severity. RESULTS: The SG and TTO measures generated higher mean (SD) utility
      scores (0.91 [0.17] and 0.94 [0.14], respectively) than the VAS, EQ-5D, and HUI3
      (0.76 [0.19], 0.82 [0.18], and 0.75 [025], respectively) (P < .001). The maximum
      score of 1.0 was reported in 60 of 99 cases (61%) for the SG and 75 of 99 cases
      (76%) for the TTO (a significant ceiling effect), in contrast to 5 of 99 cases
      (5%) for the VAS, 29 of 99 cases (29%) for the EQ-5D, and 6 of 99 cases (6%) for
      the HUI3. The VAS showed strong correlations with the EQ-5D (rho = 0.63 [P <
      .001]) and HUI3 (rho = 0.50 [P < .001]), and the HUI3 strongly correlated with
      the EQ-5D (rho = 0.67 [P < .001]), whereas the SG and TTO generally correlated
      poorly with other HU measures (rho range, 0.19-0.29) and with one another (rho =
      0.21 [P < .001]). The VAS, EQ-5D, and HUI3 were able to discriminate between
      participants who underwent salvage surgery compared with those who underwent
      primary surgery (mean [SD] utility scores, 0.48 [0.13] vs 0.76 [0.20] [P = .006],
      0.62 [0.17] vs 0.83 [0.19] [P = .004], and 0.37 [0.29] vs 0.78 [0.22] [P = .004],
      respectively). Mean EQ-5D utility scores monotonically increased over time since
      completion of treatment (0.26 [P = .01]). The HUI3 yielded lower utility values
      for participants with laryngeal cancer (mean [SD], 0.59 [0.29]). The SG and TTO
      measures frequently generated utility scores that contradicted our hypothesized
      expectations. CONCLUSIONS AND RELEVANCE: Indirect HU measures may be more
      reflective of the health status of patients with head and neck cancer than direct
      measures. Current instruments lack face validity for attributes germane to this
      population.

PMID- 26204442
TI  - Advances in graphene-based semiconductor photocatalysts for solar energy
      conversion: fundamentals and materials engineering.
AB  - Graphene-based semiconductor photocatalysis has been regarded as a promising
      technology for solar energy storage and conversion. In this review, we summarized
      recent developments of graphene-based photocatalysts, including preparation of
      graphene-based photocatalysts, typical key advances in the understanding of
      graphene functions for photocatalytic activity enhancement and methodologies to
      regulate the electron transfer efficiency in graphene-based composite
      photocatalysts, by which we hope to offer enriched information to harvest the
      utmost fascinating properties of graphene as a platform to construct efficient
      graphene-based composite photocatalysts for solar-to-energy conversion. 

PMID- 26204441
TI  - Ectopic splenic tissues mimicking gastro-intestinal stromal tumour in a patient
      after splenectomy for a giant epithelial cyst of spleen: A case report.
AB  - INTRODUCTION: Ectopic splenic tissues left after a previous splenectomy can
      masquerade as a gastro-intestinal stromal tumour (GIST). PRESENTATION OF CASE:
      Splenectomy was carried out for a 17-year-old girl with a giant epithelial cyst
      of spleen. Four years later, an upper endoscopy carried out for dyspepsia
      revealed two sub-mucosal lesions at the posterior wall of the gastric fundus.
      Computed tomography diagnosed a GIST. At operation, a dump-bell shaped
      extragastric mass was excised. Histology showed normal splenic tissues.
      DISCUSSION: Giant epithelial cyst of spleen is rare. It is even rarer for ectopic
      splenic tissues left after splenectomy to masquerade as a GIST. CONCLUSION:
      Ectopic splenic tissues should be included as a differential diagnosis in a
      patient who has a history of splenectomy presenting with a sub-mucosal gastric
      tumour.

PMID- 26204440
TI  - A diagnostic dilemma: Left-sided appendicitis in a 10 year old boy with
      previously undiagnosed intestinal malrotation. A case report.
AB  - INTRODUCTION: Intestinal malrotation is a congenital rotational anomaly that
      occurs as a result of an arrest of normal rotation of the embryonic gut, said to
      occur in 1 in 6000 live births. Due to the abnormal caecal and appendix position,
      diagnosis of acute appendicitis becomes more challenging, thus leading to
      diagnostic and operative intervention delays. Our aim is to highlight the
      diagnostic challenges in this clinical scenario. PRESENTATION OF CASE: We present
      a case of a 10 year old boy with previously undiagnosed intestinal malrotation
      with a left sided acute appendicitis. Initial symptoms lead to a treatment for
      gastroenteritis, however, due to ongoing pain a CT abdomen was done which showed
      the malrotation and appendicitis. He required a laparoscopy converted to open
      appendicectomy due to an appendicecal mass. DISCUSSION: Historically, intestinal
      malrotation was thought to be a disease of infancy with infrequent occurrence
      after the age of one year. However, recent analysis has shown an increase in
      presentations after one year of life into adulthood. Thus, the prevalence of
      malrotation in children and adults over the age of one year appear to be higher
      than initially presumed. CONCLUSION: Left sided acute appendicitis is a
      diagnostic dilemma, thus often leading to management delays. It is pertinent to
      remember that malrotation of the gut is more common than previously thought, and
      not just a disease of infancy. It is advisable to consider imaging studies while
      balancing the risk-benefit-ratio of radiation exposure, especially in paediatric
      cases to cinch the diagnosis.

PMID- 26204443
TI  - Characterization of Antimicrobial Resistance in Salmonella enterica Isolated from
      Pork, Chicken Meat, and Humans in Northeastern Thailand.
AB  - A total of 221 Salmonella enterica from raw pork (n=64), raw chicken (n=80), and
      humans (n=77) were characterized for antimicrobial resistance phenotypes and
      genotypes and virulence plasmid-associated genes. Most Salmonella isolates
      (95.9%) were multidrug resistant and exhibited high resistance to
      sulfamethoxazole (96.4%), streptomycin (93.2%), spectinomycin (76.5%),
      tetracycline (73.3%), ampicillin (70.1%), and trimethoprim (60.2%). Forty-one
      percent of all isolates were intI1-positive, of which 60% carried class 1
      integrons with variable region ranging in size from 0.2 to 2.0 kb. Six integron
      profiles (IP-I to IP-VI) were defined. The dfrA12-aadA2 cassette was most
      prevalent (66.7%). Class 1 integrons with the dfrA12-aadA2 cassette in five pork
      isolates could be horizontally transferred. Three pork isolates carried
      Salmonella genomic island 1 (SGI1), of which a serovar Anatum harbored SGI1 gene
      cluster located between thdF and int2. Two single-point mutations (i.e., G-259-T
      and C-248-T) in gyrA leading to Asp-87-Tyr and Ser-83-Phe substitutions in GyrA,
      respectively, were detected. Of all plasmid-mediated quinolone resistance genes
      tested, only qnrS (4.1%) and qnrB (1.8%) were found. The virulence plasmid
      associated genes including spvC, pefA, and rck were identified in 8.1%, 1.8%, and
      1.4% of all Salmonella isolates, respectively.

PMID- 26204445
TI  - Pulmonary Hypertension in Hereditary Hemorrhagic Telangiectasia.
AB  - BACKGROUND: A subset of patients with hereditary hemorrhagic telangiectasia (HHT)
      develops pulmonary hypertension (PH) by mechanisms including pulmonary arterial
      hypertension, high flow, and elevated pulmonary arterial wedge pressure (PAWP).
      We aimed to describe echocardiographic and hemodynamic characteristics of
      patients with coexisting HHT and PH. METHODS: We conducted a single-center cohort
      study of patients with confirmed HHT who underwent right-sided heart
      catheterization (RHC) and transthoracic two-dimensional echocardiography for
      suspected PH between June 1, 2003 and September 1, 2013 at Mayo Clinic Rochester,
      Minnesota. RESULTS: Of 38 patients with confirmed HHT who underwent RHC and
      echocardiography, 28 (74%) had a mean pulmonary artery pressure (MPAP) >= 25 mm
      Hg. Of those 28, 12 (43%) had pulmonary arterial hypertension. Two patients had
      normal PAWP and pulmonary vascular resistance (PVR), with PH secondary to either
      an atrial septal defect or high cardiac flow. Fourteen patients (50%) had
      elevated PAWP (>= 15 mm Hg), nine with evidence of high flow. RHC in all 28
      patients demonstrated a MPAP of 41 +/- 11 mm Hg, PAWP of 17 +/- 10 mm Hg, and PVR
      of 4.5 +/- 4.2 Wood units. Echocardiography demonstrated moderate/severe right
      ventricular dysfunction in nine patients (32%). The presence of PH trended toward
      worse survival (P = .06). CONCLUSIONS: PH in patients with HHT occurs by
      different mechanisms, and there is a trend toward worse survival in patients who
      develop PH despite the mechanism. The equal predilection toward all subtypes of
      PH illustrates the necessity of RHC to clarify the hemodynamics.

PMID- 26204444
TI  - Interleukin 35 Synovial Fluid Levels Are Associated with Disease Activity of
      Rheumatoid Arthritis.
AB  - OBJECTIVES: To study the association of systemic and local interleukin-35 (IL-35)
      levels in rheumatoid arthritis. METHODS: 37 patients with treatment naive early
      RA, 49 with established RA and 29 control patients with osteoarthritis (OA) were
      studied. Serum and paired synovial fluid samples were analysed for IL-35. Disease
      activity of RA patients was assessed according to the 28-Joint Count Disease
      Activity Score (DAS28). RESULTS: The levels of serum IL-35 were significantly
      higher in patients with treatment naive early RA compared to those with
      established disease and control OA subjects. In addition, serum levels of IL-35
      significantly decreased 12 weeks after initiation of glucocorticoids and
      conventional synthetic disease modifying antirheumatic drugs in patients with
      treatment naive early RA. Synovial fluid IL-35 levels were significantly higher
      in RA compared to OA patients, were significantly elevated compared to serum
      counterparts and correlated with synovial fluid leukocyte count (r=0.412;
      p<0.01), serum CRP levels (r=0.362; p<0.05) and DAS28 (r=0.430, p<0.01).
      CONCLUSION: This is the first study showing elevated circulating levels of IL-35
      in treatment naive early RA, its significant decrease after treatment initiation
      and positive association between increased synovial fluid IL-35 and disease
      activity in patients with long-lasting RA.

PMID- 26204446
TI  - Axin Regulates Dendritic Spine Morphogenesis through Cdc42-Dependent Signaling.
AB  - During development, scaffold proteins serve as important platforms for
      orchestrating signaling complexes to transduce extracellular stimuli into
      intracellular responses that regulate dendritic spine morphology and function.
      Axin ("axis inhibitor") is a key scaffold protein in canonical Wnt signaling that
      interacts with specific synaptic proteins. However, the cellular functions of
      these protein-protein interactions in dendritic spine morphology and synaptic
      regulation are unclear. Here, we report that Axin protein is enriched in synaptic
      fractions, colocalizes with the postsynaptic marker PSD-95 in cultured
      hippocampal neurons, and interacts with a signaling protein Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII) in synaptosomal fractions. Axin depletion by
      shRNA in cultured neurons or intact hippocampal CA1 regions significantly reduced
      dendritic spine density. Intriguingly, the defective dendritic spine
      morphogenesis in Axin-knockdown neurons could be restored by overexpression of
      the small Rho-GTPase Cdc42, whose activity is regulated by CaMKII. Moreover,
      pharmacological stabilization of Axin resulted in increased dendritic spine
      number and spontaneous neurotransmission, while Axin stabilization in hippocampal
      neurons reduced the elimination of dendritic spines. Taken together, our findings
      suggest that Axin promotes dendritic spine stabilization through Cdc42-dependent
      cytoskeletal reorganization.

PMID- 26204447
TI  - Atrial Fibrillation Is an Independent Risk Factor for Hospital-Acquired
      Pneumonia.
AB  - BACKGROUND: Patients who were hospitalized for community-based pneumonia
      frequently had pre-existing atrial fibrillation (AF) and had subsequent
      cardiovascular complications. Whether patients who had AF would be susceptible to
      the development of hospital-acquired pneumonia (HAP) is a serious concern but
      this has not been investigated. In our clinics, we have made empirical
      observation of such susceptibility. OBJECTIVES: To investigate the association
      between newly developed HAP and pre-existing AF, and to identify whether AF is an
      independent risk factor for HAP. METHODS: Hospital data from 8657 sequentially
      admitted inpatients [1059 patients with AF and 7598 without AF (NAF)] were
      collected from the Department of Cardiology, First Affiliated Hospital of Shantou
      University Medical College, Shantou, China, from January 1, 2009 to December 31,
      2011. Exclusion criteria were: having previous or current pneumonia, pacemakers,
      sick sinus syndrome and repeated hospitalization. The incidence of HAP (within 48
      hours after hospitalization) was identified among all the patients. RESULTS:
      Among the AF patients, 274 had HAP (adjusted rate 25.64%) which was significantly
      higher than the 276 NAF patients who had HAP (adjusted rate 3.66%; P<0.001). The
      increased risk was also associated with high blood pressure, heart failure and
      age, but not with gender, smoking, coronary heart disease, diabetes, congenital
      heart disease. In addition, our multiple regression analysis indicates that AF is
      an independent risk factor for HAP. CONCLUSION: We have identified, for the first
      time, that AF is an important risk factor for HAP. Although additional clinical
      confirmation is needed, our data provide valuable evidence for use in prevention
      of HAP which is the most common cause of death from nosocomial infection.

PMID- 26204448
TI  - Effect of Global Regulators RpoS and Cyclic-AMP/CRP on the Catabolome and
      Transcriptome of Escherichia coli K12 during Carbon- and Energy-Limited Growth.
AB  - For heterotrophic microbes, limited availability of carbon and energy sources is
      one of the major nutritional factors restricting the rate of growth in most
      ecosystems. Physiological adaptation to this hunger state requires metabolic
      versatility which usually involves expression of a wide range of different
      catabolic pathways and of high-affinity carbon transporters; together, this
      allows for simultaneous utilization of mixtures of carbonaceous compounds at low
      concentrations. In Escherichia coli the stationary phase sigma factor RpoS and
      the signal molecule cAMP are the major players in the regulation of transcription
      under such conditions; however, their interaction is still not fully understood.
      Therefore, during growth of E. coli in carbon-limited chemostat culture at
      different dilution rates, the transcriptomes, expression of periplasmic proteins
      and catabolomes of strains lacking one of these global regulators, either rpoS or
      adenylate cyclase (cya), were compared to those of the wild-type strain. The
      inability to synthesize cAMP exerted a strong negative influence on the
      expression of alternative carbon source uptake and degradation systems. In
      contrast, absence of RpoS increased the transcription of genes belonging to high
      affinity uptake systems and central metabolism, presumably due to reduced
      competition of sigma(D) with sigma(S). Phenotypical analysis confirmed this
      observation: The ability to respire alternative carbon substrates and to express
      periplasmic high-affinity binding proteins was eliminated in cya and crp mutants,
      while these properties were not affected in the rpoS mutant. As expected,
      transcription of numerous stress defence genes was negatively affected by the
      rpoS knock-out mutation. Interestingly, several genes of the RpoS stress response
      regulon were also down-regulated in the cAMP-negative strain indicating a
      coordinated global regulation. The results demonstrate that cAMP is crucial for
      catabolic flexibility during slow, carbon-limited growth, whereas RpoS is
      primarily involved in the regulation of stress response systems necessary for the
      survival of this bacterium under hunger conditions.

PMID- 26204450
TI  - The Determinants of Costs and Length of Stay for Hip Fracture Patients.
AB  - BACKGROUND AND PURPOSE: An ageing population at greater risk of proximal femoral
      fracture places an additional clinical and financial burden on hospital and
      community medical services. We analyse the variation in i) length of stay (LoS)
      in hospital and ii) costs across the acute care pathway for hip fracture from
      emergency admission, to hospital stay and follow-up outpatient appointments.
      PATIENTS AND METHODS: We analyse patient-level data from England for 2009/10 for
      around 60,000 hip fracture cases in 152 hospitals using a random effects
      generalized linear multi-level model where the dependent variable is given by the
      patient's cost or length of stay (LoS). We control for socio-economic
      characteristics, type of fracture and intervention, co-morbidities, discharge
      destination of patients, and quality indicators. We also control for provider and
      social care characteristics. RESULTS: Older patients and those from more deprived
      areas have higher costs and LoS, as do those with specific co-morbidities or that
      develop pressure ulcers, and those transferred between hospitals or readmitted
      within 28 days. Costs are also higher for those having a computed tomography (CT)
      scan or cemented arthroscopy. Costs and LoS are lower for those admitted via a
      24h emergency department, receiving surgery on the same day of admission, and
      discharged to their own homes. INTERPRETATION: Patient and treatment
      characteristics are more important as determinants of cost and LoS than provider
      or social care factors. A better understanding of the impact of these
      characteristics can support providers to develop treatment strategies and
      pathways to better manage this patient population.

PMID- 26204449
TI  - Application of wMelPop Wolbachia Strain to Crash Local Populations of Aedes
      aegypti.
AB  - The endosymbiotic bacteria Wolbachia pipientis (wMel strain) has been
      successfully established in several populations of Aedes aegypti, the primary
      dengue vector. The virulent Wolbachia strain wMelPop is known to cause several
      pathological impacts (increased egg mortality, life shortening, etc.) reducing
      overall fitness in the mosquito Ae. aegypti. Increased egg mortality could
      substantially reduce egg banks in areas with a lengthy monsoonal dry season, and
      be employed to eliminate local populations. We tested this application under semi
      field cage conditions. First, we determined that wMelPop infection significantly
      reduced the survival of desiccation-resistant eggs of the dengue vector Ae.
      aegypti, with shade and temperature having a significant impact; nearly all
      wMelPop-infected eggs failed to hatch after 6 and 10 weeks in summer and winter
      conditions, respectively. In laboratory selection experiments we found that egg
      desiccation resistance can be increased by selection, and that this effect of
      wMelPop infection is due to the nuclear background of the host rather than
      Wolbachia. We then conducted an invasion of wMelPop within a semi-field cage
      using sustained weekly releases of wMelPop infected mosquitoes, with fixation
      achieved after 9 weeks. The egg populations wMelPop infected and an uninfected
      control were then subjected to a simulated prolonged monsoonal dry season (2.5
      months) before flooding to induce hatching. The wMelPop infected eggs suffered
      significantly greater mortality than the controls, with only 0.67% and 4.35% of
      respective infected and uninfected eggs held in 99% shade hatching after 80 days.
      These studies suggest that wMelPop could be used to locally eliminate populations
      of Ae. aegypti that are exposed to prolonged dry conditions, particularly if
      combined with vector control. 

PMID- 26204451
TI  - Markets, Herding and Response to External Information.
AB  - We focus on the influence of external sources of information upon financial
      markets. In particular, we develop a stochastic agent-based market model
      characterized by a certain herding behavior as well as allowing traders to be
      influenced by an external dynamic signal of information. This signal can be
      interpreted as a time-varying advertising, public perception or rumor, in favor
      or against one of two possible trading behaviors, thus breaking the symmetry of
      the system and acting as a continuously varying exogenous shock. As an
      illustration, we use a well-known German Indicator of Economic Sentiment as
      information input and compare our results with Germany's leading stock market
      index, the DAX, in order to calibrate some of the model parameters. We study the
      conditions for the ensemble of agents to more accurately follow the information
      input signal. The response of the system to the external information is maximal
      for an intermediate range of values of a market parameter, suggesting the
      existence of three different market regimes: amplification, precise assimilation
      and undervaluation of incoming information. 

PMID- 26204452
TI  - Inhibition of insulin amyloid fibril formation by cyclodextrins.
AB  - Localized insulin-derived amyloid masses occasionally form at the site of
      repeated insulin injections in patients with insulin-dependent diabetes and cause
      subcutaneous insulin resistance. Various kinds of insulin including porcine
      insulin, human insulin, and insulin analogues reportedly formed amyloid fibrils
      in vitro and in vivo, but the impact of the amino acid replacement in insulin
      molecules on amyloidogenicity is largely unknown. In the present study, we
      demonstrated the difference in amyloid fibril formation kinetics of human insulin
      and insulin analogues, which suggests an important role of the C-terminal domain
      of the insulin B chain in nuclear formation of amyloid fibrils. Furthermore, we
      determined that cyclodextrins, which are widely used as drug carriers in the
      pharmaceutical field, had an inhibitory effect on the nuclear formation of
      insulin amyloid fibrils. These findings have significant implications for the
      mechanism underlying insulin amyloid fibril formation and for developing optimal
      additives to prevent this subcutaneous adverse effect. 

PMID- 26204453
TI  - Breast Cancer in Young Women: Rare Disease or Public Health Problem?

PMID- 26204454
TI  - Early versus delayed post-operative bathing or showering to prevent wound
      complications.
AB  - BACKGROUND: Many people undergo surgical operations during their life-time, which
      result in surgical wounds. After an operation the incision is closed using
      stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of
      the surgical procedure and before the patient leaves the operating theatre, the
      surgeon covers the closed surgical wound using gauze and adhesive tape or an
      adhesive tape containing a pad (a wound dressing) that covers the surgical wound.
      There is currently no guidance about when the wound can be made wet by post
      operative bathing or showering. Early bathing may encourage early mobilisation of
      the patient, which is good after most types of operation. Avoiding post-operative
      bathing or showering for two to three days may result in accumulation of sweat
      and dirt on the body. Conversely, early washing of the surgical wound may have an
      adverse effect on healing, for example by irritating or macerating the wound, and
      disturbing the healing environment. OBJECTIVES: To compare the benefits (such as
      potential improvements to quality of life) and harms (potentially increased wound
      related morbidity) of early post-operative bathing or showering (i.e. within 48
      hours after surgery, the period during which epithelialisation of the wound
      occurs) compared with delayed post-operative bathing or showering (i.e. no
      bathing or showering for over 48 hours after surgery) in patients with closed
      surgical wounds. SEARCH METHODS: We searched The Cochrane Wounds Group
      Specialised Register (30th June 2015); The Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of
      Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In
      Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the
      metaRegister of Controlled Trials (mRCT) and the International Clinical Trials
      Registry Platform (ICTRP). SELECTION CRITERIA: We considered all randomised
      trials conducted in patients who had undergone any surgical procedure and had
      surgical closure of their wounds, irrespective of the location of the wound and
      whether or not the wound was dressed. We excluded trials if they included
      patients with contaminated, dirty or infected wounds and those that included open
      wounds. We also excluded quasi-randomised trials, cohort studies and case-control
      studies. DATA COLLECTION AND ANALYSIS: We extracted data on the characteristics
      of the patients included in the trials, risk of bias in the trials and outcomes
      from each trial. For binary outcomes, we calculated the risk ratio (RR) with 95%
      confidence interval (CI). For continuous variables we planned to calculate the
      mean difference (MD), or standardised mean difference (SMD) with 95% CI. For
      count data outcomes, we planned to calculate the rate ratio (RaR) with 95% CI. We
      used RevMan 5 software for performing these calculations. MAIN RESULTS: Only one
      trial was identified for inclusion in this review. This trial was at a high risk
      of bias. This trial included 857 patients undergoing minor skin excision surgery
      in the primary care setting. The wounds were sutured after the excision. Patients
      were randomised to early post-operative bathing (dressing to be removed after 12
      hours and normal bathing resumed) (n = 415) or delayed post-operative bathing
      (dressing to be retained for at least 48 hours before removal and resumption of
      normal bathing) (n = 442). The only outcome of interest reported in this trial
      was surgical site infection (SSI). There was no statistically significant
      difference in the proportion of patients who developed SSIs between the two
      groups (857 patients; RR 0.96; 95% CI 0.62 to 1.48). The proportions of patients
      who developed SSIs were 8.5% in the early bathing group and 8.8% in the delayed
      bathing group. AUTHORS' CONCLUSIONS: There is currently no conclusive evidence
      available from randomised trials regarding the benefits or harms of early versus
      delayed post-operative showering or bathing for the prevention of wound
      complications, as the confidence intervals around the point estimate are wide,
      and, therefore, a clinically significant increase or decrease in SSI by early
      post-operative bathing cannot be ruled out. We recommend running further
      randomised controlled trials to compare early versus delayed post-operative
      showering or bathing.

PMID- 26204455
TI  - Probing the Protonation State and the Redox-Active Sites of Pendant Base Iron(II)
      and Zinc(II) Pyridinediimine Complexes.
AB  - Utilizing the pyridinediimine ligand [(2,6
      (i)PrC6H3)N?CMe)(N((i)Pr)2C2H4)N?CMe)C5H3N] (didpa), the zinc(II) and iron(II)
      complexes Zn(didpa)Cl2 (1), Fe(didpa)Cl2 (2), [Zn(Hdidpa)Cl2][PF6] (3),
      [Fe(Hdidpa)Cl2][PF6] (4), Zn(didpa)Br2 (5), and [Zn(Hdidpa)Br2][PF6] (6),
      Fe(didpa)(CO)2 (7), and [Fe(Hdidpa)(CO)2][PF6] (8) were synthesized and
      characterized. These complexes allowed for the study of the secondary
      coordination sphere pendant base and the redox-activity of the didpa ligand
      scaffold. The protonated didpa ligand is capable of forming metal halogen
      hydrogen bonds (MHHBs) in complexes 3, 4, and 6. The solution behavior of the
      MHHBs was probed via pKa measurements and (1)H NMR titrations of 3 and 6 with
      solvents of varying H-bond accepting strength. The H-bond strength in 3 and 6 was
      calculated in silico to be 5.9 and 4.9 kcal/mol, respectively. The relationship
      between the protonation state and the ligand-based redox activity was probed
      utilizing 7 and 8, where the reduction potential of the didpa scaffold was found
      to shift by 105 mV upon protonation of the reduced ligand in Fe(didpa)(CO)2. 

PMID- 26204456
TI  - A rare case of osteoblastoma associated to aneurysmal bone cyst of the spine.
      Case report.
AB  - Osteoblastoma is a rare bone tumour. It is occasionally associated with an
      aneurysmal bone cyst (ABC). Several treatment strategies can be adopted. We
      report a challenging case of an osteoblastoma associated with ABC of the lumbar
      spine in a 2-year-old boy. The pathogenesis and the critical management of the
      disease are discussed. 

PMID- 26204457
TI  - Reply to De Witte et al - Language therapists for language testing in awake
      craniotomy.

PMID- 26204458
TI  - Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and
      the platelet receptors GPIb and PAR4.
AB  - Thrombin is a central regulator of leukocyte recruitment and inflammation at
      sites of vascular injury, a function thought to involve primarily endothelial PAR
      cleavage. Here we demonstrate the existence of a distinct leukocyte-trafficking
      mechanism regulated by components of the haemostatic system, including platelet
      PAR4, GPIbalpha and fibrin. Utilizing a mouse endothelial injury model we show
      that thrombin cleavage of platelet PAR4 promotes leukocyte recruitment to sites
      of vascular injury. This process is negatively regulated by GPIbalpha, as seen in
      mice with abrogated thrombin-platelet GPIbalpha binding (hGPIbalpha(D277N)). In
      addition, we demonstrate that fibrin limits leukocyte trafficking by forming a
      physical barrier to intravascular leukocyte migration. These studies demonstrate
      a distinct 'checkpoint' mechanism of leukocyte trafficking involving balanced
      thrombin interactions with PAR4, GPIbalpha and fibrin. Dysregulation of this
      checkpoint mechanism is likely to contribute to the development of
      thromboinflammatory disorders. 

PMID- 26204460
TI  - Effects of CLOCK gene variants and early stress on hopelessness and suicide in
      bipolar depression.
AB  - BACKGROUND: Patients with mood disorders show a high dependence of behavior on
      the molecular characteristics of the biological clock. CLOCK rs1801260 gene
      polymorphism influences circadian behavior in bipolar disorder (BD), with *C
      carriers showing a delayed sleep onset and worse insomnia. Sleep phase delay and
      insomnia associate with suicide in the general population. METHODS: We
      investigated the effects of rs1801260, and of exposure to stressful life events,
      on current suicidal ideation and history of suicide attempts in 87 depressed
      patients with BD. RESULTS: rs1801260*C carriers currently showed worse Hamilton
      Depression Rating Scale scores for suicide and worse ratings for depressive
      cognitive distortions. Previous history of attempted suicide associated with
      exposure to higher stressful events in the early life, with rs1801260*C carriers
      showing a higher dependency of the modeled probability of attempting suicide on
      the severity of exposure to early stress. DISCUSSION: CLOCK rs1801260 modulated
      the relationship between early stress, adult history of attempted suicide and
      current suicide ideation. Factors affecting the biological clock can influence
      "non-clock" core psychopathological features of mood disorders.

PMID- 26204464
TI  - Bioenergetic Analysis of Single Pancreatic beta-Cells Indicates an Impaired
      Metabolic Signature in Type 2 Diabetic Subjects.
AB  - Impaired activation of mitochondrial energy metabolism by glucose has been
      demonstrated in type 2 diabetic beta-cells. The cause of this dysfunction is
      unknown. The aim of this study was to identify segments of energy metabolism with
      normal or with altered function in human type 2 diabetes mellitus. The
      mitochondrial membrane potential (DeltapsiM), and its response to glucose, is the
      main driver of mitochondrial ATP synthesis and is hence a central mediator of
      glucose-induced insulin secretion, but its quantitative determination in beta
      cells from human donors has not been attempted, due to limitations in assay
      technology. Here, novel fluorescence microscopic assays are exploited to quantify
      DeltapsiM and its response to glucose and other secretagogues in beta-cells of
      dispersed pancreatic islet cells from 4 normal and 3 type 2 diabetic organ
      donors. Mitochondrial volume densities and the magnitude of DeltapsiM in low
      glucose were not consistently altered in diabetic beta-cells. However, DeltapsiM
      was consistently less responsive to elevation of glucose concentration, whereas
      the decreased response was not observed with metabolizable secretagogue mixtures
      that feed directly into the tricarboxylic acid cycle. Single-cell analysis of the
      heterogeneous responses to metabolizable secretagogues indicated no dysfunction
      in relaying DeltapsiM hyperpolarization to plasma membrane potential
      depolarization in diabetic beta-cells. DeltapsiM of diabetic beta-cells was
      distinctly responsive to acute inhibition of ATP synthesis during glucose
      stimulation. It is concluded that the mechanistic deficit in glucose-induced
      insulin secretion and mitochondrial hyperpolarization of diabetic human beta
      cells is located upstream of the tricarboxylic acid cycle and manifests in
      dampening the control of DeltapsiM by glucose metabolism. 

PMID- 26204465
TI  - Critical Care Transesophageal Echocardiography.
AB  - Critical care transesophageal echocardiography (TEE) is useful in characterizing
      shock states encountered by intensivists when transthoracic echocardiography
      (TTE) gives insufficient information or when more detailed analysis of cardiac
      structures is needed. It is safe, feasible, and easy to learn and is a
      recommended component of advanced critical care echocardiography. This article
      reviews critical care TEE regarding training, equipment, comparison with TTE,
      indications, safety, and standard views of critical care TEE. It should be
      considered a companion article to a recent two-part series in CHEST that focused
      on advanced critical care TTE. Included with this article is an online supplement
      that has a representative series of critical care TEE images with clinical
      commentary. 

PMID- 26204462
TI  - Glucocorticoid-Induced Preterm Birth and Neonatal Hyperglycemia Alter Ovine beta
      Cell Development.
AB  - Adults born preterm are at increased risk of impaired glucose tolerance and
      diabetes. Late gestation fetuses exposed to high blood glucose concentration also
      are at increased risk of impaired glucose tolerance as adults. Preterm babies
      commonly become hyperglycemic and are thus exposed to high blood glucose
      concentration at an equivalent stage of pancreatic maturation. It is not known
      whether preterm birth itself, or complications of prematurity, such as
      hyperglycemia, alter later pancreatic function. To distinguish these, we made
      singleton preterm lambs hyperglycemic (HYPER) for 12 days after birth with a
      dextrose infusion and compared them with vehicle-treated preterm and term
      controls and with HYPER lambs made normoglycemic with an insulin infusion.
      Preterm birth reduced beta-cell mass, apparent by 4 weeks after term and
      persisting to adulthood (12 mo), and was associated with reduced insulin
      secretion at 4 months (juvenile) and reduced insulin mRNA expression in
      adulthood. Hyperglycemia in preterm lambs further down-regulated key pancreatic
      gene expression in adulthood. These findings indicate that reduced beta-cell mass
      after preterm birth may be an important factor in increased risk of diabetes
      after preterm birth and may be exacerbated by postnatal hyperglycemia. 

PMID- 26204461
TI  - Observation of universal strong orbital-dependent correlation effects in iron
      chalcogenides.
AB  - Establishing the appropriate theoretical framework for unconventional
      superconductivity in the iron-based materials requires correct understanding of
      both the electron correlation strength and the role of Fermi surfaces. This
      fundamental issue becomes especially relevant with the discovery of the iron
      chalcogenide superconductors. Here, we use angle-resolved photoemission
      spectroscopy to measure three representative iron chalcogenides, FeTe0.56Se0.44,
      monolayer FeSe grown on SrTiO3 and K0.76Fe1.72Se2. We show that these
      superconductors are all strongly correlated, with an orbital-selective strong
      renormalization in the dxy bands despite having drastically different Fermi
      surface topologies. Furthermore, raising temperature brings all three compounds
      from a metallic state to a phase where the dxy orbital loses all spectral weight
      while other orbitals remain itinerant. These observations establish that iron
      chalcogenides display universal orbital-selective strong correlations that are
      insensitive to the Fermi surface topology, and are close to an orbital-selective
      Mott phase, hence placing strong constraints for theoretical understanding of
      iron-based superconductors. 

PMID- 26204466
TI  - Psychosocial Functioning and Health-Related Quality of Life Associated with
      Posttraumatic Stress Disorder in Male and Female Iraq and Afghanistan War
      Veterans: The VALOR Registry.
AB  - OBJECTIVES: Iraq and Afghanistan war veterans suffer from high rates of
      posttraumatic stress disorder (PTSD). Given the growing number of women in the
      military, there is a critical need to understand the nature and extent of
      potential gender differences in PTSD-associated psychosocial functioning and
      health-related quality of life (HRQOL) in Operation Enduring Freedom
      (OEF)/Operation Iraqi Freedom (OIF) veterans, which has not been studied to date.
      METHODS: We used data from a gender-balanced national patient registry of warzone
      deployed OEF/OIF veterans (Project VALOR: Veterans After-Discharge Longitudinal
      Registry) to determine the impact of gender on PTSD-related psychosocial
      functioning and HRQOL in 1,530 United States Iraq and Afghanistan war veterans
      (50% female) with and without PTSD. Overall psychosocial functioning was assessed
      with the Inventory of Psychosocial Functioning (IPF) and mental and physical
      HRQOL with the Veterans RAND 12-item Health Survey (VR-12) Mental and Physical
      Component Summary scores, respectively. Stratified linear regression models
      estimated gender-specific associations, controlling for demographic, deployment,
      and postdeployment factors. Interaction models tested for significant effect
      moderation by gender. RESULTS: In gender-stratified models, PTSD was strongly
      associated with higher IPF scores (greater functional impairment), with similar
      associations by gender. PTSD was also associated with lower Mental Component
      Summary scores (lower mental HRQOL) in both men and women, with no evidence of
      effect moderation by gender. PTSD was associated with lower Physical Component
      Summery scores in women but not men in adjusted models; however, interactions
      were not significant. CONCLUSION: PTSD among warzone-deployed OEF/OIF veterans is
      associated with significant impairments in both overall psychosocial functioning
      and HRQOL, with associations that are largely similar by gender. Findings support
      the need for thorough and continuous assessment of functional impairment and
      HRQOL during treatment of PTSD for both male and female OEF/OIF veterans.

PMID- 26204463
TI  - Neonatal Progesterone Programs Adult Uterine Responses to Progesterone and
      Susceptibility to Uterine Dysfunction.
AB  - In this report, we investigated the consequences of neonatal progesterone
      exposure on adult rat uterine function. Female pups were subcutaneously injected
      with vehicle or progesterone from postnatal days 3 to 9. Early progesterone
      exposure affected endometrial gland biogenesis, puberty, decidualization, and
      fertility. Because decidualization and pregnancy success are directly linked to
      progesterone action on the uterus, we investigated the responsiveness of the
      adult uterus to progesterone. We first identified progesterone-dependent uterine
      gene expression using RNA sequencing and quantitative RT-PCR in Holtzman Sprague
      Dawley rats and progesterone-resistant Brown Norway rats. The impact of neonatal
      progesterone treatment on adult uterine progesterone responsiveness was next
      investigated using quantitative RT-PCR. Progesterone resistance affected the
      spectrum and total number of progesterone-responsive genes and the magnitude of
      uterine responses for a subset of progesterone targets. Several progesterone
      responsive genes in adult uterus exhibited significantly dampened responses in
      neonatally progesterone-treated females compared with those of vehicle-treated
      controls, whereas other progesterone-responsive transcripts did not differ
      between female rats exposed to vehicle or progesterone as neonates. The
      organizational actions of progesterone on the uterus were dependent on signaling
      through the progesterone receptor but not estrogen receptor 1. To summarize,
      neonatal progesterone exposure leads to disturbances in endometrial gland
      biogenesis, progesterone resistance, and uterine dysfunction. Neonatal
      progesterone effectively programs adult uterine responsiveness to progesterone. 

PMID- 26204469
TI  - Single-Nucleotide Polymorphisms on the RYD5 Gene in Nasal Polyposis.
AB  - Nasal polyposis (NP) is a chronic inflammatory disease. Several genes play major
      roles in the pathophysiology of the disease. We analyzed RYD5 gene polymorphisms
      to determine the effect of these variants or their genetic combinations on NP. We
      genotyped the RYD5 gene in 434 participants (196 patients with NP and 238
      controls). Data were analyzed with SPSS, SNPStats, and multifactor dimensionality
      reduction (MDR) software. We genotyped 10 single-nucleotide polymorphisms (SNPs)
      in the RYD5 gene. RYD5 (+152G>T) (p.Gly51Va) has not been reported previously.
      The PolyPhen and PROVEAN predicted the missense mutation as deleterious, but
      sorting intolerant from tolerant (SIFT) did not. In the genotype analysis, we
      found that four SNPs (RYD5 [-264A>G], [-103G>A], [+57-14C>T], and [+66A>G]) were
      significantly associated with NP. The individuals with combined genotypes of six
      risk alleles (RYD5-264G, -103A, +13C, +57-14T, +66G, and +279T) had significantly
      higher risks for NP compared with the ones with one or four risk alleles.
      Haplotype analysis revealed that the two haplotypes were associated with risk of
      NP. As indicated by MDR analysis, RYD5 (-264A>G and -103G>A) and RYD5 (-264A>G, 
      177C>A, and -103G>A) were the best predictive combinations and they had the
      highest synergistic interaction on NP. In addition, RYD5 (+13C>T) was
      significantly associated with increased risk of both NP with asthma and NP with
      allergy and asthma. Some SNPs and their combinations in the RYD5 gene are
      associated with increased probability for developing NP. We emphasize the
      importance of genetic factors on NP and NP-related clinical phenotypes. 

PMID- 26204470
TI  - Isolated double orifice mitral valve in a young asymptomatic woman.
AB  - : Double orifice mitral valve (DOMV) is a rare congenital malformation of the
      mitral apparatus frequently associated with other congenital malformations of the
      heart, whereas the isolated form is rare. The prevalence is about 1% of
      congenital heart disease; valve stenosis and regurgitation are common findings.
      Echocardiography represents the best method to diagnose DOMV, providing both
      anatomical and functional data. We report a case of a young woman presenting with
      an isolated DOMV, in the absence of stenosis and significant regurgitation. The
      dysmorphic valve has been evaluated with both two-dimensional and three
      dimensional echocardiography, providing impressive and detailed images of the
      peculiar anatomical configuration of the valve.

PMID- 26204472
TI  - Influence of Climate on Clinical Diagnostic Dry Eye Tests: Pilot Study.
AB  - PURPOSE: To analyze dry eye disease (DED) tests and their consistency in similar
      nonsymptomatic population samples living in two geographic locations with
      different climates (Continental vs. Atlantic). METHODS: This is a pilot study
      including 14 nonsymptomatic residents from Valladolid (Continental climate,
      Spain) and 14 sex-matched and similarly aged residents from Braga (Atlantic
      climate, Portugal); they were assessed during the same season (spring) of two
      consecutive years. Phenol red thread test, conjunctival hyperemia, fluorescein
      tear breakup time, corneal and conjunctival staining, and Schirmer test were
      evaluated on three different consecutive visits. Reliability was assessed using
      the intraclass correlation coefficient and weighted kappa (kappa) coefficient for
      quantitative and ordinal variables, respectively. RESULTS: Fourteen subjects were
      recruited in each city with a mean (+/- SD) age of 63.0 (+/- 1.7) and 59.1 (+/-
      0.9) years (p = 0.08) in Valladolid and Braga, respectively. Intraclass
      correlation coefficient and kappa values of the tests performed were below 0.69
      and 0.61, respectively, for both samples, thus showing moderate to poor
      reliability. Subsequently, comparisons were made between the results
      corresponding to the middle and higher outdoor relative humidity (RH) visit in
      each location as there were no differences in mean temperature (p >= 0.75)
      despite RH values significantly differing (p <= 0.005). Significant (p <= 0.05)
      differences were observed between Valladolid and Braga samples on tear breakup
      time (middle RH visit, 2.76 +/- 0.60 vs. 5.26 +/- 0.64 seconds; higher RH visit,
      2.61 +/- 0.32 vs. 5.78 +/- 0.88 seconds) and corneal (middle RH, 0.64 +/- 0.17
      vs. 0.14 +/- 0.10; higher RH, 0.60 +/- 0.22 vs. 0.0 +/- 0.0) and conjunctival
      staining (middle RH, 0.61 +/- 0.17 vs. 0.14 +/- 0.08; higher RH, 0.57 +/- 0.15
      vs. 0.18 +/- 0.09). CONCLUSIONS: This pilot study provides initial evidence to
      support that DED test outcomes assessing the ocular surface integrity and tear
      stability are climate dependent. Future large-sample studies should support these
      outcomes also in DED patients. This knowledge is fundamental for multicenter
      clinical trials. Lack of consistency in diagnostic clinical tests for DED was
      also corroborated.

PMID- 26204471
TI  - Transmission of genital human papillomavirus infection in couples: a population
      based cohort study in rural China.
AB  - HPV transmission dynamics have rarely been studied in the general population,
      especially in China. We followed the genital HPV infection status of both
      partners in 874 couples aged 25-65 years from rural China for up to 7 bi-annual
      visits during 2009-2013. The positive HPV concordance and transmission rate for
      partners in a couple were evaluated and relevant risk factors were assessed. The
      concordance of any, oncogenic, and non-oncogenic HPV was 15.52%, 16.18% and
      10.41%, respectively. Male-to-female transmission rate was 7.11, 12.13 and
      4.77/1000 person months for any, oncogenic and non-oncogenic HPV respectively.
      The female-to-male transmission rate was 5.56, 2.37, and 17.01/1000 person months
      for any, oncogenic and non-oncogenic HPV respectively. The risk of male-to-female
      transmission was significantly higher than that of female-to-male transmission
      for oncogenic types. However, for non-oncogenic types, the risk of male-to-female
      transmission was significantly lower than that of female-to-male transmission.
      Younger couples, persistent infection with HPV, higher numbers of sexual partners
      and higher frequency of sexual intercourse were positively associated with HPV
      transmission in couples. Our results indicate that men in rural China play a more
      important role than men in western populations as a source of cervical oncogenic
      HPV infection in women. 

PMID- 26204478
TI  - ORIGAMI MODEL FOR TEACHING BINOCULAR INDIRECT OPHTHALMOSCOPY.

PMID- 26204479
TI  - ?

PMID- 26204473
TI  - "Dry Eye" Is the Wrong Diagnosis for Millions.
AB  - The clinical perspective that dry eye is, at best, an incomplete diagnosis and
      the benefit of an etiology-based approach to dry eye are presented. To provide
      context for this perspective, the historical and current definition of dry eye is
      reviewed. The paradigm shift introduced by the Meibomian Gland Dysfunction (MGD)
      Workshop, that MGD is likely the leading cause of dry eye, is discussed in
      combination with the advancements in the diagnosis and treatment of MGD. To
      facilitate discussion on the benefit of an etiology-based approach, a
      retrospective observational analysis was performed on deidentified data from
      eligible, fully consented, refractory dry eye patients, where conventional
      sequelae-based dry eye treatment had failed. In this refractory population, the
      diagnosis of MGD, which directed treatment to evacuating gland obstructions and
      rehabilitating gland function, was successful. The clinical perspective that "dry
      eye" is the wrong diagnosis for millions is provocative. However, the MGD-first
      approach has the potential to revolutionize the timing of diagnosis and the
      choice of frontline therapy in most patients with dry eye. Additionally, the
      ability to screen for MGD in its earliest stages, during routine care, expands
      the scope of clinical practice to include early intervention. For most patients,
      we are no longer constrained to delay diagnosis until the tear film has
      decompensated and the cascade of inflammation has ensued. We do not have to wait
      for our patients to tell us there is a problem. 

PMID- 26204476
TI  - Intermittent exotropia: continued controversies and current management.
AB  - PURPOSE OF REVIEW: Continued controversy exists regarding intermittent exotropia
      and its management. Although it has been studied extensively, the indication for
      and timing of intervention and what therapy is most efficacious remains unclear.
      This article reviews the most recent research and the controversies surrounding
      the disease classification and treatment options in the management of
      intermittent exotropia. RECENT FINDINGS: Current studies are underway to uncover
      the natural history of the intermittent exotropia. Patching and observation are
      reasonable treatment options in the first 6 months of the disease presentation.
      As the disease progresses and nonsurgical management fails, botulinum toxin may
      play a role or be an alternative option in the early treatment of intermittent
      exotropia. Surgical treatment with orthoptic therapy may result in improved
      postoperative outcomes. SUMMARY: Although significant investigations have been
      performed on this entity, there remains poor cohesiveness between clinical trials
      resulting in lack of clarity regarding when and how to treat intermittent
      exotropia. As the natural history of the disease is elucidated and researchers
      standardize their assessment of the control of the strabismus and what
      constitutes a successful treatment outcome, better understanding may occur to
      develop more efficacious remedies. Despite being less known and utilized,
      botulinum toxin and orthoptic therapy are options for treatment for intermittent
      exotropia and should be considered for appropriate patient's treatment protocol.

PMID- 26204474
TI  - Ocular Surface Cooling Corresponds to Tear Film Thinning and Breakup.
AB  - PURPOSE: To investigate the relationship between ocular surface temperature (OST)
      and tear film thinning and breakup. METHODS: Simultaneous imaging of OST and
      fluorescein tear thinning and breakup (FTBU) was performed on 20 subjects.
      Subjects were asked to open their eyes and refrain from blinking for as long as
      they could during testing. Ocular surface temperature was measured using an
      infrared thermographic camera (FLIR A655sc) and rates of ocular surface cooling
      (OSC) were analyzed using commercially available software. A method was developed
      to quantify the rate of FTBU formation using image-processing software. RESULTS:
      Areas of FTBU and regions of OSC were observed to be colocalized, with localized
      cooling preceding the formation of FTBU. The rates of OSC and FTBU formation were
      positively correlated (r = 0.74). A second-order polynomial model accurately
      describes the physiological relationship between the area of FTBU and OST (p <
      0.001). A linear approximation provides a more clinically interpretable rate of
      FTBU formation with decreasing OST (p < 0.001), while still retaining high R.
      CONCLUSIONS: The results suggest a direct relationship between FTBU formation and
      OSC. That cooling of the ocular surface precedes FTBU formation implies a process
      of evaporation contributing to tear film thinning and breakup. Our study suggests
      that measuring the OSC rate could be an indirect assessment of tear evaporation
      and could contribute to the management of evaporative dry eye.

PMID- 26204480
TI  - ?

PMID- 26204481
TI  - ?

PMID- 26204477
TI  - Comparison of analytic methods for quantitative real-time polymerase chain
      reaction data.
AB  - Polymerase chain reaction (PCR) is a laboratory procedure to amplify and
      simultaneously quantify targeted DNA molecules, and then detect the product of
      the reaction at the end of all the amplification cycles. A more modern technique,
      real-time PCR, also known as quantitative PCR (qPCR), detects the product after
      each cycle of the progressing reaction by applying a specific fluorescence
      technique. The quantitative methods currently used to analyze qPCR data result in
      varying levels of estimation quality. This study compares the accuracy and
      precision of the estimation achieved by eight different models when applied to
      the same qPCR dataset. Also, the study evaluates a newly introduced data
      preprocessing approach, the taking-the-difference approach, and compares it to
      the currently used approach of subtracting the background fluorescence. The
      taking-the-difference method subtracts the fluorescence in the former cycle from
      that in the latter cycle to avoid estimating the background fluorescence. The
      results obtained from the eight models show that taking-the-difference is a
      better way to preprocess qPCR data compared to the original approach because of a
      reduction in the background estimation error. The results also show that weighted
      models are better than non-weighted models, and that the precision of the
      estimation achieved by the mixed models is slightly better than that achieved by
      the linear regression models. 

PMID- 26204482
TI  - ?

PMID- 26204483
TI  - ?

PMID- 26204475
TI  - The Functional Connectome of Speech Control.
AB  - In the past few years, several studies have been directed to understanding the
      complexity of functional interactions between different brain regions during
      various human behaviors. Among these, neuroimaging research installed the notion
      that speech and language require an orchestration of brain regions for
      comprehension, planning, and integration of a heard sound with a spoken word.
      However, these studies have been largely limited to mapping the neural correlates
      of separate speech elements and examining distinct cortical or subcortical
      circuits involved in different aspects of speech control. As a result, the
      complexity of the brain network machinery controlling speech and language
      remained largely unknown. Using graph theoretical analysis of functional MRI
      (fMRI) data in healthy subjects, we quantified the large-scale speech network
      topology by constructing functional brain networks of increasing hierarchy from
      the resting state to motor output of meaningless syllables to complex production
      of real-life speech as well as compared to non-speech-related sequential finger
      tapping and pure tone discrimination networks. We identified a segregated network
      of highly connected local neural communities (hubs) in the primary sensorimotor
      and parietal regions, which formed a commonly shared core hub network across the
      examined conditions, with the left area 4p playing an important role in speech
      network organization. These sensorimotor core hubs exhibited features of flexible
      hubs based on their participation in several functional domains across different
      networks and ability to adaptively switch long-range functional connectivity
      depending on task content, resulting in a distinct community structure of each
      examined network. Specifically, compared to other tasks, speech production was
      characterized by the formation of six distinct neural communities with
      specialized recruitment of the prefrontal cortex, insula, putamen, and thalamus,
      which collectively forged the formation of the functional speech connectome. In
      addition, the observed capacity of the primary sensorimotor cortex to exhibit
      operational heterogeneity challenged the established concept of unimodality of
      this region. 

PMID- 26204484
TI  - Nursing Practice With Incarcerated Women: A Focused Comparative Review of the
      Nursing and Feminist Literature.
AB  - Nurses who practice with criminalized women will recognize this group as
      profoundly marginalized through multiple, intersecting mechanisms. The number of
      women imprisoned in North America, Latin America, Australia, and Western Europe
      continues to rise as it has for the past 20 years or more. As a nurse who has
      practiced almost exclusively with marginalized people, I have met and cared for
      many women whose health is made vulnerable by race, poverty, homelessness, mental
      health issues, and other factors. Many of them have been repeatedly incarcerated,
      experiencing chronically destabilizing cycles of getting arrested, going to jail,
      getting out, being homeless, getting arrested again, and repeating the cycle. To
      better understand the implications for nursing with respect to criminalized
      women, a focused review of the nursing and feminist scholarly literature on
      incarcerated women was conducted. The predominant themes and trends from both
      bodies of literature are presented and cross-compared. An analysis of what each
      body of scholarly work can offer to the other, including implications for nursing
      practice, concludes the literature review. 

PMID- 26204485
TI  - Droplet spray ionization from a glass microscope slide: real-time monitoring of
      ethylene polymerization.
AB  - Ambient ionization mass spectrometry is achieved in a simple manner by loading a
      sample solution onto a corner of a microscope cover glass positioned in front of
      the inlet to a mass spectrometer and applying a high voltage to the sample. The
      resulting stream of charged droplets is stable, has no contamination from the
      substrate platform, and can be used repeatedly. The utility of droplet spray for
      in situ analysis and real-time monitoring of chemical reactions was demonstrated
      by the bis(cyclopentadienyl)zirconium dichloride (zirconocene
      dichloride)/methylaluminoxane, Cp2ZrCl2/MAO, homogeneously catalyzed
      polymerization of ethylene in various solutions. Reaction times ranged from
      seconds to minutes, and catalytically active species and polymeric products of
      ethylene were acquired and identified by tandem mass spectrometry. 

PMID- 26204486
TI  - Repeated Localized Treatment for Endobronchial Metastasis of Thymic Carcinoma.
AB  - BACKGROUND: Endobronchial metastases derived from nonpulmonary tumors are
      uncommon, although a variety of malignant tumors have been reported to be
      associated with endobronchial metastasis. We herein report a case of repeated
      bronchoscopic resection of endobronchial metastasis of a thymic carcinoma. CASE
      REPORT: A 59-year-old woman was diagnosed with primary thymic carcinoma, Masaoka
      stage IVA, in May 2009. In June 2013, she developed dyspnea. A chest CT scan
      revealed left upper lobe atelectasis, and a polypoid lesion was noted in the left
      upper bronchus on bronchoscopy. A pathological examination of the lesion revealed
      metastatic thymic carcinoma, and bronchoscopic resection was performed for
      symptom relief. However, the lesion was partially resected, based on the
      operative findings, which showed the peripheral part of B3 to be the origin of
      the polypoid lesion and bronchoscopy could not be used to reach this site.
      Although the patient underwent repeated partial bronchoscopic resection of the
      polypoid lesion due to the symptoms of dyspnea caused by regrowth of the polypoid
      metastatic thymic cancer in the left upper bronchus, she remains alive with an
      excellent performance status and no evidence of widespread or other metastases
      for more than 5 years after the initial diagnosis. CONCLUSIONS: We speculate that
      this case was successfully managed with repeated partial bronchoscopic resection
      because thymic cancer tends to be a slow-growing tumor. Therefore, it is worth
      resecting endobronchial metastatic thymic carcinoma repeatedly in such cases,
      even if the resection is partial.

PMID- 26204488
TI  - Protein tyrosine phosphatase SHP2 promotes invadopodia formation through
      suppression of Rho signaling.
AB  - Invadopodia are actin-enriched membrane protrusions that are important for
      extracellular matrix degradation and invasive cell motility. Src homolog domain
      containing phosphatase 2 (SHP2), a non-receptor protein tyrosine phosphatase, has
      been shown to play an important role in promoting cancer metastasis, but the
      underlying mechanism is unclear. In this study, we found that depletion of SHP2
      by short-hairpin RNA suppressed invadopodia formation in several cancer cell
      lines, particularly in the SAS head and neck squamous cell line. In contrast,
      overexpression of SHP2 promoted invadopodia formation in the CAL27 head and neck
      squamous cell line, which expresses low levels of endogenous SHP2. The depletion
      of SHP2 in SAS cells significantly decreased their invasive motility. The
      suppression of invadopodia formation by SHP2 depletion was restored by the
      Clostridium botulinum C3 exoenzyme (a Rho GTPase inhibitor) or Y27632 (a specific
      inhibitor for Rho-associated kinase). Together, our results suggest that SHP2 may
      promote invadopodia formation through inhibition of Rho signaling in cancer
      cells. 

PMID- 26204492
TI  - In Vitro Lung Model Assessing the Efficacy of Surgical Sealants in Treating
      Alveolar Air Leaks.
AB  - PURPOSE: The lack of reliable testing methods limits the evidence-based practice
      of surgical sealants in treating alveolar air leak (AAL). We developed an in
      vitro lung model to evaluate sealants' efficacy and tested the widely used human
      thrombin-fibrinogen sponge, TachoSil as an example. MATERIALS AND METHODS: The
      caudal lobe of freshly excised swine lung (n = 10) was intubated and ventilated.
      A focal superficial parenchymal defect (40 * 25 mm) was created in the inflated
      lung. AAL was assessed with increasing inspired tidal volume (TVi). After sealant
      application, AAL was assessed in the same way until burst failure, defined as an
      AAL exceeding 20 mL. To evaluate the elasticity of the sealant, the length of
      defect was recorded in the inflated lung. RESULTS: Superficial parenchymal
      defects resulted in AAL increasing with ascending TVi. Multiple linear regression
      analysis revealed strong correlation between AAL and maximal inspiratory
      pressure, compliance and resistance. At TVi = 400, 500, and 600 mL, TachoSil
      achieved sealing in ten, eight, and seven tests, respectively. As TVi increased,
      superficial defects were still sealed in four, two, and two tests at TVi = 700,
      800, and 900 mL, respectively. The burst pressure was 42 +/- 5 cmH2O. Adhesive
      failures were found at the burst pressure in all tests. Concerning elasticity,
      TachoSil allowed an expansion of the covered lung defect of 7 +/- 6 mm.
      CONCLUSIONS: TachoSil demonstrated a strong sealing efficiency and marked
      elasticity in treating AAL. These results are consistent to that of the
      previously published animal experiment, suggesting the reliability of the
      presented in vitro model.

PMID- 26204489
TI  - MiR-26b/KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and
      metastasis through downregulating OCT4.
AB  - Karyopherin alpha 2 (KPNA2) is a nuclear transport protein upregulated in many
      cancers. Our previous study has identified KPNA2 overexpression in epithelial
      ovarian carcinoma (EOC) tissues, which predicts poor prognosis. However, the
      mechanism of KPNA2 overexpression in EOC remains unclear. This study aimed to
      examine the role of miRNA in KPNA2 dysregulation. Our results showed that miR-26b
      was downregulated in EOC samples, and correlated inversely with KPNA2 expression.
      Low expression of miR-26b was associated with advanced FIGO stage, poor
      differentiation, higher risk of distant metastasis and recurrence. Downregulation
      of miR-26b predicted poor disease-free survival and overall survival in EOC
      patients. KPNA2 was validated as a direct target of miR-26b. Knockdown of KPNA2
      or ectopic expression of miR-26b could downregulate OCT4, vimentin and upregulate
      E-cadherin. Reintroduction of KPNA2 partially abrogated the suppression effect
      induced by miR-26b. We further verified that miR-26b/KPNA2/OCT4 axis inhibited
      EOC cell viability, migratory ability and sphere-forming capacity in vitro and in
      vivo. In conclusion, our results reveal that miR-26b is downregulated in EOC, and
      directly targets KPNA2. miR-26b/KPNA2 axis suppresses tumor proliferation and
      metastasis through decreasing OCT4 expression, which is indicative of the
      important role of miR-26b/KPNA2/OCT4 axis in EOC carcinogenesis and progression. 

PMID- 26204495
TI  - ER stress mediates homocysteine-induced endothelial dysfunction: Modulation of
      IKCa and SKCa channels.
AB  - OBJECTIVE: It remains incompletely understood how homocysteine impairs
      endothelial function. Whether mechanisms such as calcium-activated potassium
      (KCa) channels are involved is uncertain and the significance of endoplasmic
      reticulum (ER) stress in KCa channel-dependent endothelial function in
      hyperhomocysteinemia remains unexplored. We investigated the effect of
      homocysteine on endothelial KCa channels in coronary vasculature with further
      exploration of the role of ER stress. METHODS: Vasorelaxation mediated by
      intermediate- and small-conductance KCa (IKCa and SKCa) channels was studied in
      porcine coronary arteries in a myograph. IKCa and SKCa channel currents were
      recorded by whole-cell patch-clamp in coronary endothelial cells. Protein levels
      of endothelial IKCa and SKCa channels were determined for both whole-cell and
      surface expressions. RESULTS: Homocysteine impaired bradykinin-induced IKCa and
      SKCa-dependent EDHF-type relaxation and attenuated the vasorelaxant response to
      the channel activator. IKCa and SKCa currents were suppressed by homocysteine.
      Inhibition of ER stress during homocysteine exposure enhanced IKCa and SKCa
      currents, associated with improved EDHF-type response and channel activator
      induced relaxation. Homocysteine did not alter whole-cell protein levels of IKCa
      and SKCa whereas lowered surface expressions of these channels, which were
      restored by ER stress inhibition. CONCLUSIONS: Homocysteine induces endothelial
      dysfunction through a mechanism involving ER stress-mediated suppression of IKCa
      and SKCa channels. Inhibition of cell surface expression of these channels by ER
      stress is, at least partially, responsible for the suppressive effect of
      homocysteine on the channel function. This study provides new mechanistic
      insights into homocysteine-induced endothelial dysfunction and advances our
      knowledge of the significance of ER stress in vascular disorders.

PMID- 26204494
TI  - Living longer by sitting less and moving more.
AB  - PURPOSE OF REVIEW: Regular exercise, physical fitness and sedentary behaviours
      are each known to be associated with cardiovascular and total mortality. This
      review evaluates recent research on these associations and its implications for
      guidelines on physical activity. RECENT FINDINGS: In several large cohort
      studies, modest levels of exercise, much less than recommended in current
      guidelines, were associated with lower mortality. Avoiding prolonged sitting has
      also been associated with lower mortality risk. Most research suggests graded
      decreases in long-term mortality with an increase in usual physical activity and
      fitness. However, at very high exercise levels, these benefits may be attenuated,
      particularly in patients with known coronary heart disease. SUMMARY: In sedentary
      persons, a modest increase in physical activity and avoiding prolonged sitting
      are likely to have important health benefits. Further research is needed to
      determine the most effective strategies for increasing physical activity.

PMID- 26204491
TI  - Cyclin-dependent kinase 2 is an ideal target for ovary tumors with elevated
      cyclin E1 expression.
AB  - CCNE1 gene amplification is present in 15-20% ovary tumor specimens. Here, we
      showed that Cyclin E1 (CCNE1) was overexpressed in 30% of established ovarian
      cancer cell lines. We also showed that CCNE1 was stained positive in over 40% of
      primary ovary tumor specimens regardless of their histological types while CCNE1
      staining was either negative or low in normal ovary and benign ovary tumor
      tissues. However, the status of CCNE1 overexpression was not associated with the
      tumorigenic potential of ovarian cancer cell lines and also did not correlate
      with pathological grades of ovary tumor specimens. Subsequent experiments with
      CCNE1 siRNAs showed that knockdown of CCNE1 reduced cell growth only in cells
      with inherent CCNE1 overexpression, indicating that these cells may have
      developed an addiction to CCNE1 for growth/survival. As CCNE1 is a regulatory
      factor of cyclin-dependent kinase 2 (Cdk2), we investigated the effect of Cdk2
      inhibitor on ovary tumorigenecity. Ovarian cancer cells with elevated CCNE1
      expression were 40 times more sensitive to Cdk2 inhibitorSNS-032 than those
      without inherent CCNE1 overexpression. Moreover, SNS-032 greatly prolonged the
      survival of mice bearing ovary tumors with inherent CCNE1 overexpression. This
      study suggests that ovary tumors with elevated CCNE1 expression may be staged for
      Cdk2-targeted therapy. 

PMID- 26204496
TI  - Hematocrit and the risk of cardiovascular disease in a Japanese community: The
      Hisayama Study.
AB  - OBJECTIVES: The association between hematocrit levels and the risk of
      cardiovascular disease (CVD) has been reported inconsistently. We aimed to
      investigate the association of hematocrit levels with the development of stroke
      and coronary heart disease (CHD) in a general Japanese population. METHODS: A
      total of 2585 community-dwelling Japanese individuals aged 40 years or older in
      1988 were followed up for 19 years. These subjects were divided into four groups
      according to the sex-specific quartiles of hematocrit at baseline. RESULTS:
      During the follow-up, 301 subjects developed stroke (210 ischemic and 91
      hemorrhagic) and 187 developed CHD. The risk of ischemic stroke was higher in
      both the lowest (Q1: men, <=44.7%; women, <=39.3%) and the highest (Q4: men,
      >=49.7%; women, >=43.8%) quartiles than in the third quartile (Q3: men, 47.1%
      49.6%; women, 41.7%-43.7%) used as a reference (multivariable-adjusted hazard
      ratios [95% confidence intervals]: Q1, 1.55 [0.99-2.43]; Q2, 1.44 [0.93-2.23];
      Q3, 1.00; and Q4, 1.62 [1.06-2.50]; P = 0.86 for trend). In contrast, hematocrit
      levels and the risk of hemorrhagic stroke showed a linear inverse association
      (Q1, 1.91 [1.03-3.54]; Q2, 1.26 [0.68-2.34]; Q3, 1.00; and Q4, 0.81 [0.41-1.61];
      P = 0.009 for trend). The risk of CHD increased significantly in Q4 (Q1, 1.13
      [0.71-1.80]; Q2, 1.08 [0.69-1.71]; Q3, 1.00; and Q4, 1.60 [1.04-2.46]; P = 0.13
      for trend). CONCLUSIONS: Our findings suggest that both elevated and decreased
      hematocrit levels are associated with an increased risk of CVD, but the influence
      of hematocrit is different among subtypes of CVD.

PMID- 26204493
TI  - Herpes Simplex Virus Vector-Mediated Gene Delivery of Poreless TRPV1 Channels
      Reduces Bladder Overactivity and Nociception in Rats.
AB  - Increased afferent excitability has been proposed as an important pathophysiology
      of interstitial cystitis/bladder pain syndrome (IC/BPS) and overactive bladder
      (OAB). In this study, we investigated whether herpes simplex virus (HSV) vectors
      encoding poreless TRPV1, in which the segment in C terminus of TRPV1 receptor is
      deleted, suppress bladder overactivity and pain behavior using a rat model of
      chemical cystitis. Replication-defective HSV vectors encoding poreless TRPV1 were
      injected into the bladder wall of adult female Sprague-Dawley rats. Additionally,
      recombinant HSV virus (vHG) vectors were injected as control. Cystometry (CMG)
      under urethane anesthesia was performed 1 week after viral injection to evaluate
      bladder overactivity induced by resiniferatoxin (RTx, a TRPV1 agonist). RTx
      induced nociceptive behavior such as licking (lower abdominal licking) and
      freezing (motionless head-turning) was observed 2 weeks after viral injection.
      GFP expression in L4/L6/S1 dorsal root ganglia and the bladder as well as c-Fos
      positive cells in the L6 spinal cord dorsal horn were also evaluated 2 weeks
      after viral injection. In CMG, the poreless TRPV1 vector-treated group showed a
      significantly smaller reduction in intercontraction intervals and voided volume
      after RTx infusion than the vHG-treated control group. The number of the RTx
      induced freezing events was significantly decreased in the poreless TRPV1 group
      than in the vHG group, whereas there was no significant difference of the number
      of RTx-induced licking events between groups. The number of c-Fos-positive cells
      in the DCM and SPN regions of the L6 spinal dorsal horn was significantly smaller
      in the poreless TRPV1 group than in the vHG group. Our results indicated that HSV
      vector-mediated gene delivery of poreless TRPV1 had a therapeutic effect on TRPV1
      mediated bladder overactivity and pain behavior. Thus, the HSV vector-mediated
      gene therapy targeting TRPV1 receptors could be a novel modality for the
      treatment of OAB and/or hypersensitive bladder disorders such as IC/BPS. 

PMID- 26204490
TI  - eIF4E binding protein 1 expression is associated with clinical survival outcomes
      in colorectal cancer.
AB  - eIF4E binding protein 1 (4E-BP1), is critical for cap-dependent and cap
      independent translation. This study is the first to demonstrate that 4E-BP1
      expression correlates with colorectal cancer (CRC) progression. Compared to its
      expression in normal colon epithelial cells, 4E-BP1 was upregulated in CRC cell
      lines and was detected in patient tumor tissues. Furthermore, high 4E-BP1
      expression was statistically associated with poor prognosis. Hypoxia has been
      considered as an obstacle for cancer therapeutics. Our previous data showed that
      YXM110, a cryptopleurine derivative, exhibited anticancer activity via 4E-BP1
      depletion. Here, we investigated whether YXM110 could inhibit protein synthesis
      under hypoxia. 4E-BP1 expression was notably decreased by YXM110 under hypoxic
      conditions, implying that cap-independent translation could be suppressed by
      YXM110. Moreover, YXM110 repressed hypoxia-inducible factor 1alpha (HIF-1alpha)
      expression, which resulted in decreased downstream vascular endothelial growth
      factor (VEGF) expression. These observations highlight 4E-BP1 as a useful
      biomarker and therapeutic target, indicating that YXM110 could be a potent CRC
      therapeutic drug. 

PMID- 26204497
TI  - Use of a proximity extension assay proteomics chip to discover new biomarkers for
      human atherosclerosis.
AB  - BACKGROUND AND AIMS: We used a proteomics array to simultaneously measure
      multiple proteins that have been suggested to be associated with atherosclerosis
      and related them to plaque prevalence in carotid arteries in a human population
      based study. METHODS: In the Prospective Study of the Vasculature in Uppsala
      Seniors (PIVUS; n = 931, 50% women, all aged 70 years), the number of carotid
      arteries with plaques was recorded by ultrasound. Levels of 82 proteins were
      assessed in plasma by a proximity extension assay (Proseek Multiplex CVD, Olink
      Bioscience, Uppsala, Sweden) and related to carotid measures in a regression
      framework. RESULTS: Following adjustment for multiple testing with Bonferroni
      correction, seven of the proteins were significantly related to the number of
      carotid arteries affected by plaques in sex-adjusted models (osteoprotegrin, T
      cell immunoglobulin and mucin domain (TIM)-1, growth/differentiation factor 15
      (GDF-15), matrix metalloprotease-12 (MMP-12), renin, tumor necrosis factor ligand
      superfamily member 14 (TNFSF14) and growth hormone). Of these, renin (odds ratio
      [OR], 1.30; 95% confidence interval [CI], 1.13-1.49 per standard deviation
      increase), growth hormone (OR, 1.24; 95% CI, 1.08-1.43), osteoprotegerin (OR,
      1.22; 95% CI, 1.05-1.43) and TNFSF14 (OR, 1.17; 95% CI, 1.01-1.35) were related
      to plaque prevalence independently of each other and traditional cardiovascular
      risk factors. CONCLUSION: A novel targeted proteomics approach using the
      proximity extension technique discovered several new associations of candidate
      proteins with carotid artery plaque prevalence in a large human sample.

PMID- 26204500
TI  - Amantelides A and B, Polyhydroxylated Macrolides with Differential Broad-Spectrum
      Cytotoxicity from a Guamanian Marine Cyanobacterium.
AB  - Cytotoxicity-guided fractionation of a Guamanian cyanobacterial collection
      yielded the new compounds amantelides A (1) and B (2). These polyketides are
      characterized by a 40-membered macrolactone ring consisting of a 1,3-diol and
      contiguous 1,5-diol units and a tert-butyl substituent. Amantelide A (1)
      displayed potent cytotoxicity with submicromolar IC50 against HT29 colorectal
      adenocarcinoma and HeLa cervical carcinoma cell lines. Acetylation of the hydroxy
      group at C-33 in 2 caused a close to 10-fold decrease in potency. Exhaustive
      acetylation of the hydroxy groups abrogated the antiproliferative activity of
      amantelide A (1) by 20-67-fold. Further bioactivity assessment of 1 against
      bacterial pathogens and marine fungi indicated a broad spectrum of bioactivity.

PMID- 26204487
TI  - Down-regulation of alpha-L-fucosidase 1 expression confers inferior survival for
      triple-negative breast cancer patients by modulating the glycosylation status of
      the tumor cell surface.
AB  - alpha-L-fucosidase 1 (FUCA1) is a lysosomal enzyme that catalyzes the hydrolytic
      cleavage of the terminal fucose residue in breast cancer cells. FUCA1 mRNA levels
      were detected by real-time PCR, and there was a greater than 139-fold increase in
      FUCA1 mRNA expression in breast tumor samples compared with normal breast tissue
      samples (*P = 0.005, n = 236). Higher FUCA1 mRNA expression was preferentially
      detected in early-stage tumors (stage 0 to 2) compared with advanced-stage tumors
      (stage 3 to 4) (stage 0-1 versus stage 3, *P = 0.015; stage 0-1 versus stage 4,
      *P = 0.024). FUCA1 protein levels were higher in advanced-stage tumors
      concomitant with decreased fucosylated Lewis-x antigen expression, as evidenced
      using the immunohistochemical staining H-score method (*P < 0.001). Statistical
      analysis revealed that lower FUCA1 levels significantly predicted an inferior
      overall survival rate among triple-negative breast cancer (TNBC) patients
      compared with non-TNBC patients (*P = 0.009). Two stable FUCA1 siRNA knock-down
      MDA-MB-231 cell lines were established, and the results suggest that transient
      FUCA inhibition creates a selective pressure that triggers the metastasis of
      primary tumor cells, as detected by wound healing and invasion assays (*P <
      0.01). The results suggest that FUCA1 may be a potential prognostic molecular
      target for clinical use, especially in TNBC patients. 

PMID- 26204498
TI  - Antitumoral gene-based strategy involving nitric oxide synthase type III
      overexpression in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma develops in cirrhotic liver. The nitric oxide (NO)
      synthase type III (NOS-3) overexpression induces cell death in hepatoblastoma
      cells. The study developed gene therapy designed to specifically overexpress NOS
      3 in cultured hepatoma cells, and in tumors derived from orthotopically implanted
      tumor cells in fibrotic livers. Liver fibrosis was induced by CCl4 administration
      in mice. The first-generation adenoviruses were designed to overexpress NOS-3 or
      green fluorescent protein, and luciferase complementary DNA under the regulation
      of murine alpha-fetoprotein (AFP) and Rous Sarcoma Virus (RSV) promoters,
      respectively. Both adenovirus and Hepa 1-6 cells were used for in vitro and in
      vivo experiments. Adenoviruses were administered through the tail vein 2 weeks
      after orthotopic tumor cell implantation. AFP-NOS-3/RSV-luciferase increased
      oxidative-related DNA damage, p53, CD95/CD95L expression and caspase-8, -9 and -3
      activities in cultured Hepa 1-6 cells. The increased expression of CD95/CD95L and
      caspase-8 activity was abolished by Nomega-nitro-l-arginine methyl ester
      hydrochloride, p53 and CD95 small interfering RNA. AFP-NOS-3/RSV-luciferase
      adenovirus increased cell death markers, and reduced cell proliferation of
      established tumors in fibrotic livers. The increase of oxidative/nitrosative
      stress induced by NOS-3 overexpression induced DNA damage, p53, CD95/CD95L
      expression and cell death in hepatocellular carcinoma cells. The effectiveness of
      the gene therapy has been demonstrated in vitro and in vivo. 

PMID- 26204506
TI  - Role of SrO on the bioactivity behavior of some ternary borate glasses and their
      glass ceramic derivatives.
AB  - Borate glasses containing SrO substituting both CaO and NaO were prepared and
      characterized for their bioactivity or bone bonding ability. Glass ceramic
      derivatives were prepared by thermal heat treatment process. FTIR, XRD and SEM
      measurements for the prepared glass and glass-ceramics before and after immersion
      in sodium phosphate solution for one and two weeks were carried out. The
      appearance of two IR peaks within the range 550-680cm(-1) after immersion in
      phosphate solution indicates the formation of hydroxyapatite or equivalent Sr
      phosphate layer. X-ray diffraction data agree with the FTIR spectral analysis.
      The solubility test was carried out for both glasses and glass ceramics
      derivatives in the same phosphate solution. The introduction of SrO increases the
      solubility for both glasses and glass ceramics and this is assumed to be due to
      the formation of Sr phosphate which is more soluble than calcium phosphate
      (hydroxyapatite). SEM images reveal varying changes in the surfaces of glass
      ceramics after immersion according to the SrO content.

PMID- 26204511
TI  - 1,8-Bis(phenylethynyl)anthracene - gas and solid phase structures.
AB  - 1,8-Bis(phenylethynyl)anthracene (1,8-BPEA) was synthesized by a twofold Kumada
      cross-coupling reaction. The molecular structure of 1,8-BPEA was determined using
      a combination of gas-phase electron diffraction (GED), mass spectrometry (MS),
      quantum chemical calculations (QC) and single-crystal X-ray diffraction (XRD).
      Five rotamers of the molecule with different orientations of phenylethynyl groups
      were investigated by DFT calculations. According to these, molecules of C2
      symmetry with co-directional rotation of the phenylethynyl groups are predicted
      to exist in the gas phase at 498 K. This was confirmed by a GED/MS experiment at
      this temperature. The bonding of this conformer was studied and described in
      terms of an NBO-analysis. Dispersion interactions in the solid state structure
      and in the free molecule are discussed. In the solid this symmetry is broken; the
      asymmetric unit of the single crystal contains 3.5 molecules and a herringbone
      packing motif of pi-stacked dimers and trimers. The pi-stacking in the dimers is
      between the anthracene units, and the trimers are linked by pi-stacking between
      phenyl and anthracene units. The interaction between these stacks can be
      described in terms of sigma(C-H)pi interactions. 

PMID- 26204507
TI  - Design, synthesis and evaluation of novel polypharmacological antichlamydial
      agents.
AB  - Discovery of new polypharmacological antibacterial agents with multiple modes of
      actions can be an alternative to combination therapy and also a possibility to
      slow development of antibiotic resistance. In support to this hypothesis, we
      synthesized 16 compounds by combining the pharmacophores of Chlamydia trachomatis
      inhibitors and inhibitors of type III secretion (T3S) in gram-negative bacteria.
      In this study we have developed salicylidene acylhydrazide sulfonamides (11c
      &11d) as new antichlamydial agents that also inhibit T3S in Yersinia
      pseudotuberculosis. 

PMID- 26204499
TI  - Hematopoietic knockdown of PPARdelta reduces atherosclerosis in LDLR-/- mice.
AB  - PPARdelta (peroxisome proliferator-activated receptor delta) mediates
      inflammation in response to lipid accumulation. Systemic administration of a
      PPARdelta agonist can ameliorate atherosclerosis. Paradoxically, genetic deletion
      of PPARdelta in hematopoietic cells led to a reduction of atherosclerosis in
      murine models, suggesting that downregulation of PPARdelta expression in these
      cells may mitigate atherogenesis. To advance this finding forward to potential
      clinical translation through hematopoietic stem cell transplantation-based gene
      therapy, we employed a microRNA (miRNA) approach to knock down PPARdelta
      expression in bone marrow cells followed by transplantation of the cells into
      LDLR-/- mice. We found that knockdown of PPARdelta expression in the
      hematopoietic system caused a dramatic reduction in aortic atherosclerotic
      lesions. In macrophages, a key component in atherogenesis, knockdown of PPARdelta
      led to decreased expression of multiple pro-inflammatory factors, including
      monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-1beta and IL-6.
      Expression of CCR2, a receptor for MCP-1, was also decreased. The downregulation
      of pro-inflammatory factors is consistent with significant reduction of
      macrophage presence in the lesions, which may also be attributable to elevation
      of ABCA1 (ATP-binding cassette, subfamily A, member 1) and depression of
      adipocyte differentiate-related protein. Furthermore, the abundance of both MCP-1
      and matrix metalloproteinase-9 proteins was reduced in plaque areas. Our results
      demonstrate that miRNA-mediated PPARdelta knockdown in hematopoietic cells is
      able to ameliorate atherosclerosis. 

PMID- 26204508
TI  - Preliminary research on 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2
      ol as a novel brain hypoxia PET tracer in a rodent model of stroke.
AB  - The synthesis of the new radiotracer precursor 4-Br-NITTP and the radiolabeling
      of the new tracer 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol (4
      Br-[(18)F]FMISO) is reported. The cyclic voltammetry behaviour, neuronal cell
      toxicity, transport through the brain endothelial cell monolayer, in vivo PET
      imaging and preliminary calculations of the tracer uptake for a rodent model of
      stroke were studied for the new compound and the results were compared to those
      obtained with [(18)F]FMISO, the current gold standard PET hypoxia tracer. The new
      PET brain hypoxia tracer is more easily reduced, has higher CLogP than
      [(18)F]FMISO and it diffuses more rapidly through brain endothelial cells. The
      new compound is non-toxic to neuronal cells and it allows the in vivo mapping of
      stroke in mice with higher sensitivity. 4-Br-[(18)F]FMISO is a good candidate for
      further development in ischemic stroke. 

PMID- 26204501
TI  - Dual ligand immunoliposomes for drug delivery to the brain.
AB  - Drug delivery systems that can reach brain areas affected by amyloid deposits are
      still underdeveloped. We propose pegylated liposomes functionalized with two
      antibodies, the anti-transferrin receptor monoclonal antibody (OX26MAb) and the
      anti-amyloid beta peptide antibody (19B8MAb), as nanocarriers of drugs for
      Alzheimer's disease therapy. Two distinct conjugation methods are investigated.
      In one formulation, the OX26MAb is conjugated to the tip of polyethylene glycol
      molecules through the maleimide group and the 19B8MAb is bound through the
      streptavidin-biotin complex. In the second system the conjugation reagents are
      swapped between the antibodies. Fluorescence spectroscopy experiments on porcine
      brain capillary endothelial cells show that the cellular uptake of the
      immunoliposomes is substantially more efficient if OX26MAb antibody is conjugated
      through the streptavidin-biotin complex instead of the maleimide group. The
      ability of the immunoliposomes to cross the blood brain barrier was established
      by in vivo studies in wild type rats. Our results demonstrate the importance of
      the conjugation method used to bind the antibody that targets the blood brain
      barrier to immunoliposomes for efficient drug delivery to the brain. 

PMID- 26204505
TI  - A rapid and sensitive assay for determination of doxycycline using thioglycolic
      acid-capped cadmium telluride quantum dots.
AB  - A rapid, simple and inexpensive spectrofluorimetric sensor for determination of
      doxycycline based on its interaction with thioglycolic acid-capped cadmium
      telluride quantum dots (TGA/CdTe QDs) has been developed. Under the optimum
      experimental conditions, the sensor exhibited a fast response time of <10s. The
      results revealed that doxycycline could quench the fluorescence of TGA/CdTe QDs
      via electron transfer from the QDs to doxycycline through a dynamic quenching
      mechanism. The sensor permitted determination of doxycycline in a concentration
      range of 1.9*10(-6)-6.1*10(-5)molL(-1) with a detection limit of 1.1*10(-7)molL(
      1). The sensor was applied for determination of doxycycline in honey and human
      serum samples.

PMID- 26204502
TI  - Kraft lignin/silica-AgNPs as a functional material with antibacterial activity.
AB  - Advanced functional silica/lignin hybrid materials, modified with nanosilver,
      were obtained. The commercial silica Syloid 244 was used, modified with N-(2
      aminoethyl)-3-aminopropyltrimethoxysilane to increase its chemical affinity to
      lignin. Similarly, kraft lignin was oxidized using a solution of sodium periodate
      to activate appropriate functional groups on its surface. Silver nanoparticles
      were grafted onto the resulting silica/lignin hybrids. The systems obtained were
      comprehensively tested using available techniques and methods, including
      transmission electron microscopy, Fourier transform infrared spectroscopy, energy
      dispersive X-ray spectroscopy, elemental analysis and atomic absorption
      spectroscopy. An evaluation was also made of the electrokinetic stability of the
      systems with and without silver nanoparticles. Conclusions were drawn concerning
      the chemical nature of the bonds between the precursors and the effectiveness of
      the method of binding nanosilver to the hybrid materials. The antimicrobial
      activity of the studied materials was tested against five species of Gram
      positive and Gram-negative bacteria. The addition of silver nanoparticles to the
      silica/lignin hybrids led to inhibition of the growth of the analyzed bacteria.
      The best results were obtained against Pseudomonas aeruginosa, a dangerous human
      pathogen. 

PMID- 26204510
TI  - 4-Fluoro-3',4',5'-trimethoxychalcone as a new anti-invasive agent. From discovery
      to initial validation in an in vivo metastasis model.
AB  - Invasion and metastasis are responsible for 90% of cancer-related mortality.
      Herein, we report on our quest for novel, clinically relevant inhibitors of local
      invasion, based on a broad screen of natural products in a phenotypic assay.
      Starting from micromolar chalcone hits, a predictive QSAR model for diaryl
      propenones was developed, and synthetic analogues with a 100-fold increase in
      potency were obtained. Two nanomolar hits underwent efficacy validation and
      eADMET profiling; one compound was shown to increase the survival time in an
      artificial metastasis model in nude mice. Although the molecular mechanism(s) by
      which these substances mediate efficacy remain(s) unrevealed, we were able to
      eliminate the major targets commonly associated with antineoplastic chalcones. 

PMID- 26204513
TI  - The Oncogenic Response to MiR-335 Is Associated with Cell Surface Expression of
      Membrane-Type 1 Matrix Metalloproteinase (MT1-MMP) Activity.
AB  - MicroRNA miR-335 has been reported to have both tumor suppressor and oncogenic
      activities. In order to determine possible tissue and cell type differences in
      response to miR-335, we examined the effect of miR-335 on cell expression of MT1
      MMP, a proteinase commonly expressed in tumors and associated with cell
      proliferation and migration. miR-335 increased cell surface expression of MT1-MMP
      in fibrosarcoma HT-1080 and benign prostate BPH-1 cells, but not in prostate
      LNCaP or breast MCF-7 tumor cells. miR-335 stimulated proliferation and cell
      migration in a wound healing in vitro assay in HT-1080, BPH-1, and U87
      glioblastoma cells, cells which demonstrated significant cell surface expression
      of MT1-MMP. In contrast, miR-335 did not affect proliferation or migration in
      cells without a prominent plasma membrane associated MT1-MMP activity. Our data
      suggest that differences in response to miR-335 by tumor cells may lie in part in
      the mechanism of regulation of MT1-MMP production. 

PMID- 26204504
TI  - Role of NADPH oxidases in the redox biology of liver fibrosis.
AB  - Liver fibrosis is the pathological consequence of chronic liver diseases, where
      an excessive deposition of extracellular matrix (ECM) proteins occurs,
      concomitantly with the processes of repair and regeneration. It is characterized
      by increased production of matrix proteins, in particular collagens, and
      decreased matrix remodelling. The principal source of ECM accumulation is
      myofibroblasts (MFB). Most fibrogenic MFB are endogenous to the liver, coming
      from hepatic stellate cells (HSC) and portal fibroblasts. Dysregulated
      inflammatory responses have been associated with most (if not all) hepatotoxic
      insults and chronic oxidative stress play a role during the initial liver
      inflammatory phase and its progression to fibrosis. Redox-regulated processes are
      responsible for activation of HSC to MFB, as well as maintenance of the MFB
      function. Increased oxidative stress also induces hepatocyte apoptosis, which
      contributes to increase the liver injury and to transdifferentiate HSC to MFB,
      favouring the fibrogenic process. Mitochondria and other redox-active enzymes can
      generate superoxide and hydrogen peroxide as a by-product in liver cells.
      Moreover, accumulating evidence indicates that NADPH oxidases (NOXs), which play
      a critical role in the inflammatory response, may contribute to reactive oxygen
      species (ROS) production during liver fibrosis, being important players in HSC
      activation and hepatocyte apoptosis. Based on the knowledge of the pathogenic
      role of ROS, different strategies to prevent or reverse the oxidative damage have
      been developed to be used as therapeutic tools in liver fibrosis. This review
      will update all these concepts, highlighting the relevance of redox biology in
      chronic fibrogenic liver pathologies. 

PMID- 26204503
TI  - Hydrogen peroxide signals E. coli phagocytosis by human polymorphonuclear cells;
      up-stream and down-stream pathway.
AB  - Hydrogen peroxide (Eta2Omicron2) is produced during a variety of cellular
      procedures. In this paper, the regulatory role of Eta2Omicron2, in Escherichia
      coli phagocytosis by the human polymorphonuclears, was investigated. White blood
      cells were incubated with dihydrorhodamine (DHR) in order to study H2O2 synthesis
      and E. coli-FITC to study phagocytosis. Flow cytometry revealed increased
      synthesis of H2O2 in polymorphonuclears which incorporated E. coli-FITC. The
      blocking of H2O2 synthesis by specific inhibitors, N-ethylmaleimide (NuEpsilonMU)
      for NADPH oxidase and diethyldithiocarbamate (DDC) for superoxide dismutase
      (SOD), decreased E. coli phagocytosis, as well. Immunoblot analysis of white
      blood cell protein extracts revealed that the blocking of NADPH oxidase and SOD
      decreased ERK-1/2 phosphorylation, while it had no effect on JNK and p38.
      Confocal microscopy showed that phosphorylation of MAPKs and phagocytosis solely
      occur in the polymorphonuclear and not in mononuclear cells. The use of specific
      MAPKs inhibitors showed that all of them are necessary for phagocytosis, but only
      phospho-p38 affects H2O2 synthesis. The blocking of JNK phosphorylation, in the
      presence of E. coli, evoked a further decrease of cytoplasmic p47 thus increasing
      its translocation onto the plasma membrane for the assembly of NADPH oxidase. It
      appears that newly synthesised H2O2 invigorates the phosphorylation and action of
      ERK-1/2 in E. coli phagocytosis, while phospho-JNK and phospho-p38 appear to
      regulate H2O2 production. 

PMID- 26204512
TI  - S100B Up-Regulates Macrophage Production of IL1beta and CCL22 and Influences
      Severity of Retinal Inflammation.
AB  - S100B is a Ca2+ binding protein and is typically associated with brain and CNS
      disorders. However, the role of S100B in an inflammatory situation is not clear.
      The aim of the study was to determine whether S100B is likely to influence
      inflammation through its effect on macrophages. A murine macrophage cell line
      (RAW 264.7) and primary bone marrow derived macrophages were used for in vitro
      studies and a model of retinal inflammatory disease in which pathogenesis is
      highly dependent on macrophage infiltration, Experimental Autoimmune
      Uveoretinitis, for in vitro study. Experimental Autoimmune Uveoretinitis is a
      model for the human disease posterior endogenous uveoretinitis, a potentially
      blinding condition, with an autoimmune aetiology, that mainly affects the working
      age group. To date the involvement of S100B in autoimmune uveoretinitis has not
      been investigated. Real-time PCR array analysis on RAW 246.7 cells indicated up
      regulation of gene expression for various cytokines/chemokines in response to
      S100B, IL-1beta and CCL22 in particular and this was confirmed by real-time PCR.
      In addition flow cytometry and ELISA confirmed up-regulation of protein
      production in response to S100B for pro-IL-1beta and CCL22 respectively. This was
      the case for both RAW 264.7 cells and bone marrow derived macrophages. Induction
      of EAU with retinal antigen in mice in which S100B had been deleted resulted in a
      significantly reduced level of disease compared to wild-type mice, as determined
      by topical endoscopic fundus imaging and histology grading. Macrophage
      infiltration was also significantly reduced in S100B deleted mice. Real-time PCR
      analysis indicated that this was associated with reduction in CCL22 and IL-1beta
      in retinas from S100B knock-out mice. In conclusion S100B augments the
      inflammatory response in uveoretinitis and this is likely to be, at least in
      part, via a direct effect on macrophages. 

PMID- 26204515
TI  - Histamine 1 Receptor Blockade Enhances Eosinophil-Mediated Clearance of Adult
      Filarial Worms.
AB  - Filariae are tissue-invasive nematodes that cause diseases such as elephantiasis
      and river blindness. The goal of this study was to characterize the role of
      histamine during Litomosoides sigmodontis infection of BALB/c mice, a murine
      model of filariasis. Time course studies demonstrated that while expression of
      histidine decarboxylase mRNA increases throughout 12 weeks of infection, serum
      levels of histamine exhibit two peaks-one 30 minutes after primary infection and
      one 8 weeks later. Interestingly, mice treated with fexofenadine, a histamine
      receptor 1 inhibitor, demonstrated significantly reduced worm burden in infected
      mice compared to untreated infected controls. Although fexofenadine-treated mice
      had decreased antigen-specific IgE levels as well as lower splenocyte IL-5 and
      IFNgamma production, they exhibited a greater than fourfold rise in eosinophil
      numbers at the tissue site where adult L. sigmodontis worms reside. Fexofenadine
      mediated clearance of L. sigmodontis worms was dependent on host eosinophils, as
      fexofenadine did not decrease worm burdens in eosinophil-deficient dblGATA mice.
      These findings suggest that histamine release induced by tissue invasive
      helminths may aid parasite survival by diminishing eosinophilic responses.
      Further, these results raise the possibility that combining H1 receptor
      inhibitors with current anthelmintics may improve treatment efficacy for filariae
      and other tissue-invasive helminths. 

PMID- 26204514
TI  - Ocular Inserts for Sustained Release of the Angiotensin-Converting Enzyme 2
      Activator, Diminazene Aceturate, to Treat Glaucoma in Rats.
AB  - The aim of this study was to develop and evaluate the effects of chitosan inserts
      for sustained release of the angiotensin-converting enzyme 2 (ACE2) activator,
      diminazene aceturate (DIZE), in experimental glaucoma. Monolayer DIZE loaded
      inserts (D+I) were prepared and characterized through swelling, attenuated total
      reflectance Fourier transformed infrared spectroscopy (ATR-FTIR), differential
      scanning calorimetry (DSC) and in vitro drug release. Functionally, the effects
      of D+I were tested in glaucomatous rats. Glaucoma was induced by weekly
      injections of hyaluronic acid (HA) into the anterior chamber and intraocular
      pressure (IOP) measurements were performed. Retinal ganglion cells (RGC) and
      optic nerve head cupping were evaluated in histological sections. Biodistribution
      of the drug was accessed by scintigraphic images and ex vivo radiation counting.
      We found that DIZE increased the swelling index of the inserts. Also, it was
      molecularly dispersed and interspersed in the polymeric matrix as a freebase.
      DIZE did not lose its chemical integrity and activity when loaded in the inserts.
      The functional evaluation demonstrated that D+I decreased the IOP and maintained
      the IOP lowered for up to one month (last week: 11.0 +/- 0.7 mmHg). This effect
      of D+I prevented the loss of RGC and degeneration of the optic nerve. No toxic
      effects in the eyes related to application of the inserts were observed.
      Moreover, biodistribution studies showed that D+I prolonged the retention of DIZE
      in the corneal site. We concluded that D+I provided sustained DIZE delivery in
      vivo, thereby evidencing the potential application of polymeric-based DIZE
      inserts for glaucoma management.

PMID- 26204518
TI  - De Novo Assembly and Annotation of the Chinese Chive (Allium tuberosum Rottler ex
      Spr.) Transcriptome Using the Illumina Platform.
AB  - Chinese chive (A. tuberosum Rottler ex Spr.) is one of the most widely cultivated
      Allium species in China. However, minimal transcriptomic and genomic data are
      available to reveal its evolution and genetic diversity. In this study, de novo
      transcriptome sequencing was performed to produce large transcript sequences
      using an Illumina HiSeq 2000 instrument. We produced 51,968,882 high-quality
      clean reads and assembled them into 150,154 contigs. A total of 60,031 unigenes
      with an average length of 631 bp were identified. Of these, 36,523 unigenes were
      homologous to existing database sequences, 35,648 unigenes were annotated in the
      NCBI non-redundant (Nr) sequence database, and 23,509 unigenes were annotated in
      the Swiss-Prot database. A total of 26,798 unigenes were assigned to 57 Gene
      Ontology (GO) terms, and 13,378 unigenes were assigned to Cluster of Orthologous
      Group categories. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathway database, we mapped 21,361 unigenes onto 128 pathways. Furthermore, 2,125
      sequences containing simple sequence repeats (SSRs) were identified. This new
      dataset provides the most comprehensive resource currently available for gene
      expression, gene discovery, and future genomic research on Chinese chive. The
      sequence resources developed in this study can be used to develop molecular
      markers that will facilitate further genetic research on Chinese chive and
      related species. 

PMID- 26204521
TI  - Trimethylenemethane diyl mediated tandem cycloaddition reactions: mechanism based
      design of synthetic strategies.
AB  - Several criteria for the measure of synthetic strategies toward "ideal synthesis"
      are available to guide the design and evaluation of the synthetic strategies
      toward the target molecules. One strategy toward "ideal synthesis" is developing
      a multistep reaction that involves dramatic change in complexity. Biogenesis of
      natural products and mechanistic investigation of complicated organic
      transformation provide good inspiration for design of new synthetic strategies.
      Trimethylenemethane diradical (TMM diyl), first introduced only as a
      theoretically interesting structure 60 years ago, gained interests of physical
      organic chemistry when it was first detected by Dowd. Study of characteristics
      and properties of TMM diyl was accelerated in a great deal when Koebrich observed
      dimeric hydrocarbon products from the reaction of 1,1-dibromo-2-methylhexa-1,5
      diene with MeLi. Berson followed the mechanistic investigation of the reaction
      that involved 2-methylenecyclopentane-1,3-diyl, and thoroughly studied physical
      and chemical properties of the TMM diyl. This lead to the development of
      intramolecular [2 + 3] TMM diyl cycloaddition reaction for the construction of
      linearly fused triquinanes by Little. We envisioned that the generation of a TMM
      diyl through cycloaddition reaction discovered by Koebrich and [2 + 3]
      cycloaddition reaction of the TMM diyl could be combined together to form
      polyquinane structures. A cycloaddition reaction sequence of generating a TMM
      diyl from a alkylidene carbene of 2-methylhexa-1,5-diene structure in the
      presence of another olefin was designed and executed to produce linearly fused
      and angularly fused triquinanes depending on the connectivity of the second
      double bond. The successful transformation also inspired design of a tandem
      cycloaddition reaction strategy of using unprecedented
      tetrahydrocyclopentapyrazole to TMM diyl transformation. The new design involves
      two [2 + 3] cycloaddition reactions of 6-diazohexa-1,2-diene with an olefin
      attached at a proper position. When a diazo functionality is produced, the
      initial [2 + 3] cycloaddition reaction generates the TMM diyl, which undergoes
      the second [2 + 3] cycloaddition reaction to form triquinanes with high
      efficiency. The first tandem strategy involves a massive reorganization of
      molecular connectivity as one C?C double bond was cleaved and four C-C bonds were
      formed. The second tandem strategy connected two double bonds with one carbon
      center to form four C-C bonds without breaking any bond. The developed tandem
      strategies were readily applied to the total synthesis of natural products,
      especially triquinanes. Thus, the total syntheses of hirsutene, ceratopicanol,
      pentalenene and panaginsene with structural revision were achieved and the
      strategy was extended to the total synthesis of crinipellins (tetraquinane
      natural products). The newly designed tandem strategies not only demonstrated the
      efficiency and effectiveness of the process but also provided future opportunity
      of studying TMM diyl mediated reactions for designing variety of synthetic
      strategies. 

PMID- 26204517
TI  - Efficacy and Cardiotoxicity of Liposomal Doxorubicin-Based Chemotherapy in
      Advanced Breast Cancer: A Meta-Analysis of Ten Randomized Controlled Trials.
AB  - BACKGROUND: Various trials have compared the efficacy and toxicity of liposomal
      doxorubicin-based chemotherapy with the conventional formulation of doxorubicin
      although arriving at inconsistent conclusions. To derive a conclusive assessment
      of the efficacy and cardiotoxicity associated with chemotherapy, we performed a
      meta-analysis by combining data from all eligible randomized controlled trials.
      METHODS: We used the PubMed database to identify relevant studies published
      through December 28, 2014. Eligible studies included randomized controlled trials
      directly comparing the efficacy and cardiotoxicity of liposomal doxorubicin-based
      chemotherapy with conventional doxorubicin in advanced breast cancer with
      adequate data. Odds ratios (ORs) or hazard ratios (HRs) with 95% confidence
      intervals (CIs) were used to assess the efficacy and cardiotoxicity in a fixed
      effects or random-effects model. RESULTS: Ten randomized controlled trials
      containing efficacy and data from a total of 2,889 advanced breast cancer
      patients were included in this report. Liposomal doxorubicin-based chemotherapy
      was associated with a significant reduction in the risk of cardiotoxicity (OR =
      0.46, 95% CI 0.23 to 0.92, p = 0.03) and a significant improvement in the overall
      response rate (ORR) (OR = 1.25, 95% CI 1.02 to 1.52, p=0.03) compared with
      conventional doxorubicin. An apparent improvement in progression-free survival
      (PFS) for patients treated with liposomal doxorubicin-based chemotherapy was
      noted; however, this difference was not significant (HR = 1.14, 95% CI 0.96 to
      1.34, p = 0.12). In terms of overall survival (OS), no significant difference
      between the two chemotherapy regimens was noted (HR = 1.00, 95% CI 0.91 to 1.10,
      p = 0.93). CONCLUSION: The results of this meta-analysis suggest that liposomal
      doxorubicin-based chemotherapy is associated with a significant improvement in
      the ORR and a significant reduction in the risk of cardiotoxicity.

PMID- 26204520
TI  - Fast Simulation of Mechanical Heterogeneity in the Electrically Asynchronous
      Heart Using the MultiPatch Module.
AB  - Cardiac electrical asynchrony occurs as a result of cardiac pacing or conduction
      disorders such as left bundle-branch block (LBBB). Electrically asynchronous
      activation causes myocardial contraction heterogeneity that can be detrimental
      for cardiac function. Computational models provide a tool for understanding
      pathological consequences of dyssynchronous contraction. Simulations of
      mechanical dyssynchrony within the heart are typically performed using the finite
      element method, whose computational intensity may present an obstacle to clinical
      deployment of patient-specific models. We present an alternative based on the
      CircAdapt lumped-parameter model of the heart and circulatory system, called the
      MultiPatch module. Cardiac walls are subdivided into an arbitrary number of
      patches of homogeneous tissue. Tissue properties and activation time can differ
      between patches. All patches within a wall share a common wall tension and
      curvature. Consequently, spatial location within the wall is not required to
      calculate deformation in a patch. We test the hypothesis that activation time is
      more important than tissue location for determining mechanical deformation in
      asynchronous hearts. We perform simulations representing an experimental study of
      myocardial deformation induced by ventricular pacing, and a patient with LBBB and
      heart failure using endocardial recordings of electrical activation, wall
      volumes, and end-diastolic volumes. Direct comparison between simulated and
      experimental strain patterns shows both qualitative and quantitative agreement
      between model fibre strain and experimental circumferential strain in terms of
      shortening and rebound stretch during ejection. Local myofibre strain in the
      patient simulation shows qualitative agreement with circumferential strain
      patterns observed in the patient using tagged MRI. We conclude that the
      MultiPatch module produces realistic regional deformation patterns in the
      asynchronous heart and that activation time is more important than tissue
      location within a wall for determining myocardial deformation. The CircAdapt
      model is therefore capable of fast and realistic simulations of dyssynchronous
      myocardial deformation embedded within the closed-loop cardiovascular system. 

PMID- 26204516
TI  - The Grapevine VvPMEI1 Gene Encodes a Novel Functional Pectin Methylesterase
      Inhibitor Associated to Grape Berry Development.
AB  - Pectin is secreted in a highly methylesterified form and partially de
      methylesterified in the cell wall by pectin methylesterases (PMEs). PME activity
      is expressed during plant growth, development and stress responses. PME activity
      is controlled at the post-transcriptional level by proteins named PME inhibitors
      (PMEIs). We have identified, expressed and characterized VvPMEI1, a functional
      PME inhibitor of Vitis vinifera. VvPMEI1 typically affects the activity of plant
      PMEs and is inactive against microbial PMEs. The kinetics of PMEI-PME
      interaction, studied by surface plasmon resonance, indicates that the inhibitor
      strongly interacts with PME at apoplastic pH while the stability of the complex
      is reduced by increasing the pH. The analysis of VvPMEI1 expression in different
      grapevine tissues and during grape fruit development suggests that this inhibitor
      controls PME activity mainly during the earlier phase of berry development. A
      proteomic analysis performed at this stage indicates a PME isoform as possible
      target of VvPMEI1. 

PMID- 26204509
TI  - Small lipidated anti-obesity compounds derived from neuromedin U.
AB  - A small library of truncated/lipid-conjugated neuromedin U (NmU) analogs was
      synthesized and tested in vitro using an intracellular calcium signaling assay.
      The selected, most active analogs were then tested in vivo, and showed potent
      anorexigenic effects in a diet-induced obese (DIO) mouse model. The most
      promising compound, NM4-C16 was effective in a once-weekly-dose regimen.
      Collectively, our findings suggest that short, lipidated analogs of NmU are
      suitable leads for the development of novel anti-obesity therapeutics. 

PMID- 26204519
TI  - Biological effects of alpha-radiation exposure by (241)Am in Arabidopsis thaliana
      seedlings are determined both by dose rate and (241)Am distribution.
AB  - Human activity has led to an increasing amount of radionuclides in the
      environment and subsequently to an increased risk of exposure of the biosphere to
      ionising radiation. Due to their high linear energy transfer, alpha-emitters form
      a threat to biota when absorbed or integrated in living tissue. Among these,
      (241)Am is of major concern due to high affinity for organic matter and high
      specific activity. This study examines the dose-dependent biological effects of
      alpha-radiation delivered by (241)Am at the morphological, physiological and
      molecular level in 14-day old seedlings of Arabidopsis thaliana after hydroponic
      exposure for 4 or 7 days. Our results show that (241)Am has high transfer to the
      roots but low translocation to the shoots. In the roots, we observed a
      transcriptional response of reactive oxygen species scavenging and DNA repair
      pathways. At the physiological and morphological level this resulted in a
      response which evolved from redox balance control and stable biomass at low dose
      rates to growth reduction, reduced transfer and redox balance decline at higher
      dose rates. This situation was also reflected in the shoots where, despite the
      absence of a transcriptional response, the control of photosynthesis performance
      and redox balance declined with increasing dose rate. The data further suggest
      that the effects in both organs were initiated in the roots, where the highest
      dose rates occurred, ultimately affecting photosynthesis performance and carbon
      assimilation. Though further detailed study of nutrient balance and (241)Am
      localisation is necessary, it is clear that radionuclide uptake and distribution
      is a major parameter in the global exposure effects on plant performance and
      health. 

PMID- 26204522
TI  - Mass partitioning effects in diffusion transport.
AB  - Frequent mass exchange takes place in a heterogeneous environment among several
      phases, where mass partitioning may occur at the interface of phases. Analytical
      and computational methods for diffusion do not usually incorporate molecule
      partitioning masking the true picture of mass transport. Here we present a
      computational finite element methodology to calculate diffusion mass transport
      with a partitioning phenomenon included and the analysis of the effects of
      partitioning. Our numerical results showed that partitioning controls
      equilibrated mass distribution as expected from analytical solutions. The
      experimental validation of mass release from drug-loaded nanoparticles showed
      that partitioning might even dominate in some cases with respect to diffusion
      itself. The analysis of diffusion kinetics in the parameter space of partitioning
      and diffusivity showed that partitioning is an extremely important parameter in
      systems, where mass diffusivity is fast and that the concentration of
      nanoparticles can control payload retention inside nanoparticles. The
      computational and experimental results suggest that partitioning and
      physiochemical properties of phases play an important, if not crucial, role in
      diffusion transport and should be included in the studies of mass transport
      processes. 

PMID- 26204523
TI  - Biochar Supported Nanoscale Iron Particles for the Efficient Removal of Methyl
      Orange Dye in Aqueous Solutions.
AB  - The presence of organic contaminants in industrial effluents is an environmental
      concern of increasing global importance. One innovative technology for treating
      contaminated industrial effluents is nanoscale zero-valent iron supported on
      biochar (nZVI/BC). Based on Transmission Electron Microscopy, X-Ray Diffraction,
      and Brunauer-Emmett-Teller characterizations, the nZVI was well dispersed on the
      biochar and aggregation was dramatically reduced. Methyl orange (MO) served as
      the representative organic contaminant for verifying the effectiveness of the
      composite. Using decolorization efficiency as an indicator of treatment
      effectiveness, increasing doses of nZVI/BC yielded progressively better results
      with 98.51% of MO decolorized by 0.6 g/L of composite at an nZVI/BC mass ratio of
      1:5. The superior decolorization efficiency of the nZVI/BC was attributed to the
      increase in the dispersion and reactivity of nZVI while biochar increasing the
      contact area with contaminant and the adsorption of composites. Additionally, the
      buffering function of acid-washed biochar could be in favor of maintaining the
      reactivity of nZVI. Furthermore, the aging nZVI/BC for 30 day was able to
      maintain the removal efficiency indicating that the oxidation of nZVI may be
      delayed in the presence of biochar. Therefore, the composite of nZVI/BC could
      represent an effective functional material for treating wastewater containing
      organic dyes in the future. 

PMID- 26204524
TI  - Probing the Interoceptive Network by Listening to Heartbeats: An fMRI Study.
AB  - Exposure to cues of homeostatic relevance (i.e. heartbeats) is supposed to
      increase the allocation of attentional resources towards the cue, due to its
      importance for self-regulatory, interoceptive processes. This functional magnetic
      resonance imaging (fMRI) study aimed at determining whether listening to
      heartbeats is accompanied by activation in brain areas associated with
      interoception, particularly the insular cortex. Brain activity was measured with
      fMRI during cue-exposure in 36 subjects while listening to heartbeats vs. sinus
      tones. Autonomic markers (skin conductance) and subjective measures of state and
      trait anxiety were assessed. Stimulation with heartbeat sounds triggered
      activation in brain areas commonly associated with the processing of
      interoceptive information, including bilateral insular cortices, the inferior
      frontal operculum, and the middle frontal gyrus. A psychophysiological
      interaction analysis indicated a functional connectivity between the middle
      frontal gyrus (seed region) and bilateral insular cortices, the left amygdala and
      the supplementary motor area. The magnitude of neural activation in the right
      anterior insular cortex was positively associated with autonomic arousal. The
      present findings indicate that listening to heartbeats induced activity in areas
      of the interoception network as well as changes in psychophysiological arousal
      and subjective emotional experience. As this approach constitutes a promising
      method for studying interoception in the fMRI environment, a clinical application
      in anxiety prone populations should be addressed by future studies. 

PMID- 26204525
TI  - Quantification of Leishmania (Viannia) Kinetoplast DNA in Ulcers of Cutaneous
      Leishmaniasis Reveals Inter-site and Inter-sampling Variability in Parasite Load.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is a skin disease caused by the
      protozoan parasite Leishmania. Few studies have assessed the influence of the
      sample collection site within the ulcer and the sampling method on the
      sensitivity of parasitological and molecular diagnostic techniques for CL.
      Sensitivity of the technique can be dependent upon the load and distribution of
      Leishmania amastigotes in the lesion. METHODOLOGY/PRINCIPAL FINDINGS: We applied
      a quantitative real-time PCR (qPCR) assay for Leishmania (Viannia) minicircle
      kinetoplast DNA (kDNA) detection and parasite load quantification in biopsy and
      scraping samples obtained from 3 sites within each ulcer (border, base, and
      center) as well as in cytology brush specimens taken from the ulcer base and
      center. A total of 248 lesion samples from 31 patients with laboratory confirmed
      CL of recent onset (<=3 months) were evaluated. The kDNA-qPCR detected Leishmania
      DNA in 97.6% (242/248) of the examined samples. Median parasite loads were
      significantly higher in the ulcer base and center than in the border in biopsies
      (P<0.0001) and scrapings (P = 0.0002). There was no significant difference in
      parasite load between the ulcer base and center (P = 0.80, 0.43, and 0.07 for
      biopsy, scraping, and cytology brush specimens, respectively). The parasite load
      varied significantly by sampling method: in the ulcer base and center, the
      descending order for the parasite load levels in samples was: cytology brushes,
      scrapings, and biopsies (P<0.0001); in the ulcer border, scrapings had higher
      parasite load than biopsies (P<0.0001). There was no difference in parasite load
      according to L. braziliensis and L. peruviana infections (P = 0.4).
      CONCLUSION/SIGNIFICANCE: Our results suggest an uneven distribution of Leishmania
      amastigotes in acute CL ulcers, with higher parasite loads in the ulcer base and
      center, which has implications for bedside collection of diagnostic specimens.
      The use of scrapings and cytology brushes is recommended instead of the more
      invasive biopsy.

PMID- 26204527
TI  - Multifunctional pi-expanded oligothiophene macrocycles.
AB  - This tutorial review summarizes recent progress in the design, synthesis, and
      multifunctional properties of fully conjugated macrocyclic pi-systems. We focus
      on the pi-expanded oligothiophene macrocycles after a short survey of macrocyclic
      conjugated loops and belts such as [n]cycloparaphenylenes, cyclic[n]para
      phenylacetylenes, [4]cyclo-2,8-crysenylenes, and cyclo[n]thiophenes. Fully
      conjugated pi-expanded oligothiophene macrocycles possess shape-persistent but
      sometimes pliable pi-frames, and the electronic and optoelectronic properties of
      the macrocycles largely depend on the pi-systems inserted into the oligothiophene
      macrocycles. Among them, the pi-expanded oligothiophene macrocycle composed of
      2,5-thienylenes, ethynylenes, and vinylenes is one of the most widely applicable
      macrocycles for constructing multifunctional pi-systems. These pi-expanded
      oligothiophene macrocycles from small to very large ring sizes can be prepared
      via a short step procedure, and their various solid state structures can be
      determined by X-ray analysis. Since these macrocycles have inner and outer
      domains, specific information concerning structural, electronic, and optical
      properties is expected. Furthermore, pi-expanded oligothiophene macrocycles with
      alkyl substituents exhibit various morphologies depending on nanophase separation
      of molecules, and a morphological change is observed for the molecular switch. 

PMID- 26204526
TI  - Engineering of a Biomimetic Pericyte-Covered 3D Microvascular Network.
AB  - Pericytes enveloping the endothelium play an important role in the physiology and
      pathology of microvessels, especially in vessel maturation and stabilization.
      However, our understanding of fundamental pericyte biology is limited by the lack
      of a robust in vitro model system that allows researchers to evaluate the
      interactions among multiple cell types in perfusable blood vessels. The present
      work describes a microfluidic platform that can be used to investigate
      interactions between pericytes and endothelial cells (ECs) during the sprouting,
      growth, and maturation steps of neovessel formation. A mixture of ECs and
      pericytes was attached to the side of a pre-patterned three dimensional fibrin
      matrix and allowed to sprout across the matrix. The effects of intact coverage
      and EC maturation by the pericytes on the perfused EC network were confirmed
      using a confocal microscope. Compared with EC monoculture conditions, EC-pericyte
      co-cultured vessels showed a significant reduction in diameter, increased numbers
      of junctions and branches and decreased permeability. In response to biochemical
      factors, ECs and pericytes in the platform showed the similar features with
      previous reports from in vivo experiments, thus reflect various
      pathophysiological conditions of in vivo microvessels. Taken together, these
      results support the physiological relevancy of our three-dimensional microfluidic
      culture system but also that the system can be used to screen drug effect on EC
      pericyte biology. 

PMID- 26204528
TI  - Investigation of In-Water and Dry-Land Training Programs for Competitive Swimmers
      in the United States.
AB  - CONTEXT: Youth- through masters-level competitive swimmers incur significant
      shoulder pain. Risk factors associated with shoulder pain include high swimming
      yardage, a lack of cross-training, decreased shoulder strength and reduced core
      endurance, and limited posterior shoulder and pectoral length. Since training,
      swimming exposure, and physical-performance measures have all been associated
      with shoulder pain, the methods used to train swimmers may influence the
      development of shoulder pain, yet studies delineating training methods are
      lacking. OBJECTIVES: To identify in-water and dry-land practices among youth-
      through masters-level swimmers in the United States (US) and describe the
      potential effects of training practices on swimmers' shoulders. DESIGN: A Web
      based survey was developed to identify common training practices in 5 areas:
      quantification of swimming and dry-land training and in-water techniques such as
      kicking drills, upper-body stretching, shoulder and core strengthening, and cross
      training. PARTICIPANTS: 156 swim-team coaches or captains of youth, high school,
      and college swim teams and 196 masters swimmers participated (N = 352). There was
      geographic representation from across the US. RESULTS: Responses indicated
      diverse training practices. However, most respondents used kicking drills, which
      may provoke shoulder pain due to prolonged poor positioning. High yardage swum by
      high school and college teams increases their risk of shoulder tendinopathy.
      Stretching and strengthening exercises and dosages commonly used were
      inconsistent with current research recommendations and lacked specificity in
      terms of addressing typical mobility restrictions and muscle weaknesses described
      in the swimming literature. Core strengthening and cross-training are frequently
      performed. CONCLUSIONS: Several areas of in-water and dry-land practice were
      identified that may put swimmers' shoulders at risk for injury. Further research
      regarding the safety and efficacy of training programs is recommended to
      determine optimal methods of injury prevention and performance enhancement.

PMID- 26204529
TI  - Modular Small Diameter Vascular Grafts with Bioactive Functionalities.
AB  - We report the fabrication of a novel type of artificial small diameter blood
      vessels, termed biomimetic tissue-engineered blood vessels (bTEBV), with a
      modular composition. They are composed of a hydrogel scaffold consisting of two
      negatively charged natural polymers, alginate and a modified chitosan, N,O
      carboxymethyl chitosan (N,O-CMC). Into this biologically inert scaffold two
      biofunctionally active biopolymers are embedded, inorganic polyphosphate (polyP)
      and silica, as well as gelatin which exposes the cell recognition signal, Arg-Gly
      Asp (RGD). These materials can be hardened by exposure to Ca(2+) through
      formation of Ca(2+) bridges between the polyanions, alginate, N,O-CMC, and polyP
      (alginate-Ca(2+)-N,O-CMC-polyP). The bTEBV are formed by pressing the hydrogel
      through an extruder into a hardening solution, containing Ca(2+). In this
      universal scaffold of the bTEBV biomaterial, polycations such as poly(L-Lys),
      poly(D-Lys) or a His/Gly-tagged RGD peptide (three RGD units) were incorporated,
      which promote the adhesion of endothelial cells to the vessel surface. The
      mechanical properties of the biopolymer material (alginate-Ca(2+)-N,O-CMC-polyP
      silica) revealed a hardness (elastic modulus) of 475 kPa even after a short
      incubation period in CaCl2 solution. The material of the artificial vascular
      grafts (bTEBVs with an outer size 6 mm and 1.8 mm, and an inner diameter 4 mm and
      0.8 mm, respectively) turned out to be durable in 4-week pulsatile flow
      experiments at an alternating pressure between 25 and 100 mbar (18.7 and 75.0 mm
      Hg). The burst pressure of the larger (smaller) vessels was 850 mbar (145 mbar).
      Incorporation of polycationic poly(L-Lys), poly(D-Lys), and especially the
      His/Gly-tagged RGD peptide, markedly increased the adhesion of human, umbilical
      vein/vascular endothelial cells, EA.HY926 cells, to the surface of the hydrogel.
      No significant effect of the polyP samples on the clotting of human plasma is
      measured. We propose that the metabolically degradable polymeric scaffold bTEBV
      is a promising biomaterial for future prosthetic vascular grafts.

PMID- 26204531
TI  - [Long-term results of intracoronary transplantation of autologous bone marrow
      cells in dilated cardiomyopathy].
AB  - BACKGROUND: Intracoronary delivery of autologous bone marrow mononuclear cells is
      an interesting therapeutic promise for patients with heart failure of different
      etiologies. AIM: To evaluate the long-term safety and efficacy of this therapy in
      patients with dilated cardiomyopathy of different etiologies under optimal
      medical treatment. PATIENTS AND METHODS: Prospective, open-label, controlled
      clinical trial. Of 23 consecutive patients, 12 were assigned to autologous bone
      marrow mononuclear cell intracoronary transplantation, receiving a mean dose of
      8.19 +/- 4.43 x 10(6) CD34+ cells. Mortality, cardiovascular readmissions and
      cancer incidence rate, changes in functional capacity, quality of life
      questionnaires and echocardiographic measures from baseline, were assessed at
      long-term follow-up (37.7 +/- 9.7 months) in patients receiving or not the cells.
      RESULTS: No significant differences were observed in mortality, cardiovascular
      readmissions or cancer incidence rate amongst groups. An improvement in
      functional class and quality of life questionnaires in the transplanted group was
      observed (p < 0.01). The treated group showed a non-significant increase in left
      ventricular ejection fraction at long-term follow-up (from 26.75 +/- 4.85% to
      34.90 +/- 8.57%, p = 0.059 compared to baseline). There were no changes in left
      ventricular volumes. We observed no improvement of these variables in the control
      group. CONCLUSIONS: Intracoronary transplantation of autologous bone marrow
      mononuclear cells is feasible and safe in patients with dilated cardiomyopathy of
      diverse etiologies. This therapy was associated to persistent improvements in
      functional class and quality of life. There was also a non-significant long-term
      improvement of left ventricular function.

PMID- 26204532
TI  - [Barriers restricting postpartum depression treatment in Chile].
AB  - BACKGROUND: In Chile, postpartum depression is a prevalent and disabling
      condition. Universal screening is available but has not been translated into
      better treatment rates, suggesting the existence of access barriers. AIM: To
      describe access barriers to postpartum depression treatment in six primary health
      care clinics in Metropolitan Santiago, Chile. MATERIAL AND METHODS: Twenty women
      with postpartum depression and 18 primary health care professionals were
      subjected to a semi-structured interview. A qualitative methodology based on
      Grounded Theory was used. RESULTS: There are user associated barriers such as
      lack of knowledge about the disease, a negative conceptualization and rejection
      of available treatment options. There are also barriers associated with poor
      network support and some features of the health care system such as long waiting
      times and lack of coordination between clinical and administrative decisions.
      CONCLUSIONS: Patient and provider related barriers restricting treatment of
      postpartum depression were identified.

PMID- 26204530
TI  - Genome-Wide Mapping of Collier In Vivo Binding Sites Highlights Its Hierarchical
      Position in Different Transcription Regulatory Networks.
AB  - Collier, the single Drosophila COE (Collier/EBF/Olf-1) transcription factor, is
      required in several developmental processes, including head patterning and
      specification of muscle and neuron identity during embryogenesis. To identify
      direct Collier (Col) targets in different cell types, we used ChIP-seq to map Col
      binding sites throughout the genome, at mid-embryogenesis. In vivo Col binding
      peaks were associated to 415 potential direct target genes. Gene Ontology
      analysis revealed a strong enrichment in proteins with DNA binding and/or
      transcription-regulatory properties. Characterization of a selection of
      candidates, using transgenic CRM-reporter assays, identified direct Col targets
      in dorso-lateral somatic muscles and specific neuron types in the central nervous
      system. These data brought new evidence that Col direct control of the expression
      of the transcription regulators apterous and eyes-absent (eya) is critical to
      specifying neuronal identities. They also showed that cross-regulation between
      col and eya in muscle progenitor cells is required for specification of muscle
      identity, revealing a new parallel between the myogenic regulatory networks
      operating in Drosophila and vertebrates. Col regulation of eya, both in specific
      muscle and neuronal lineages, may illustrate one mechanism behind the
      evolutionary diversification of Col biological roles. 

PMID- 26204533
TI  - [Bronchoscopy with transbronchial biopsy for the diagnosis of potentially
      malignant pulmonary lesions: experience in 261 patients].
AB  - BACKGROUND: Bronchoscopy is a minimally invasive procedure used for the diagnosis
      of lung cancer. AIM: To report our experience with bronchoscopy and
      transbronchial biopsies for the diagnosis of potentially malignant pulmonary
      lesions. MATERIAL AND METHODS: Revision of electronic records from patients who
      underwent transbronchial biopsies seeking for lung cancer. The diagnostic yield
      of the procedure was evaluated using pathology reports or a 24 months follow up.
      RESULTS: 261 patients were included. Bronchoscopy was diagnostic in 65% of cases.
      Lesions mean diameter was 51 mm (range 9-120 mm). Diagnostic yield for lesions
      less than 30 mm was 59%, for lesions less than 35 mm was 61%, and for lesions
      over 40 mm was 69%. The presence of malignant lesions and their location in the
      superior or middle lobe were associated with a better predictive value of the
      procedure. TNM staging was IIIB/IV in 80% of the patient at the time of
      diagnosis. CONCLUSIONS: The diagnostic yield of bronchoscopy is influenced by the
      etiology and location of lung lesions.

PMID- 26204534
TI  - [Amerindian admixture estimation based on serological and molecular methods].
AB  - BACKGROUND: Amerindian admixture is an important parameter to consider in
      epidemiological studies in American countries, to make a proper selection of
      cases and controls. AIM: To compare Amerindian admixture estimates obtained using
      ABO*A and ABO*O blood group alleles and ancestral identity markers (AIMs) in the
      mixed Chilean population. SUBJECTS AND METHODS: Amerindian admixture rates were
      determined in 720 Chilean volunteers residing in Arica and born in the 15 regions
      of the country, using ABO*O and ABO*A alleles and 40 AIMs selected from more than
      500,000 single nucleotide polymorphisms (SNPs). RESULTS: Mean admixture estimates
      obtained using ABO*O and ABO*A alleles and AIMs were 35, 47% and 48%
      respectively. There was concordance in estimates, with the exception of the
      admixture based on ABO*O allele and AIMs. CONCLUSIONS: In Chile, Amerindian
      admixture estimates obtained using ABO*A could be used as an alternative to AIMs
      in justified cases provided the sample size is reasonably large.

PMID- 26204535
TI  - [Association between NAT2 polymorphisms with non-syndromic cleft lip with or
      without cleft palate in Argentina].
AB  - BACKGROUND: NAT genes are considered candidate genes for the genetic
      predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP),
      since they codify for N-acetyltransferases, enzymes responsible for the
      biotransformation of arylamines, hydrazine drugs, and a great number of toxins
      and carcinogens present in diet, cigarette smoke, and environment. AIM: To
      determine the association between alleles determining slow acetylator phenotype
      and the risk of NSCLP. MATERIAL AND METHODS: We analyzed *5 (481C>T), *6 (590G>A)
      and *7 (857G>A) alleles which determine the slow acetylator phenotype and *4
      (wild type) allele by polymerase chain reaction/restriction fragment length
      polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards.
      We evaluated the transmission disequilibrium (TDT). RESULTS: TDT showed a
      positive association between allele *5 and NSCLP (odds ratio = 1,6; p = 0,03).
      CONCLUSIONS: The presence of *5 allele is significantly higher in cases with
      congenital NSCLP.

PMID- 26204536
TI  - [High rates of overweight and obesity in Chilean children with Down syndrome].
AB  - BACKGROUND: Overweight and obesity in Down syndrome (DS) is a common problem.
      Chile has a high prevalence of DS. AIM: To determine overweight and obesity rates
      in students with DS and evaluate the concordance of three different growth
      charts. MATERIAL AND METHODS: Seventy nine students with DS aged between 6 and 18
      years (56% males), from three different schools, were included. Weight and height
      were measured and their body mass index (BMI) was calculated. The nutritional
      diagnosis was made according to BMI. Myrelid SDM/2002, National Center for Health
      Statistics (NCHS)/2000, World Health Organization (WHO)/2007 charts for people
      with DS were used. RESULTS: Thirty percent of participants had hypothyroidism,
      22.8% congenital heart disease and 5% asthma. Overweight and obesity rates
      according to SDM/2002, NCHS/2000 and WHO/2007 were 43, 57 and 66% respectively.
      The concordance between WHO/2007 and NCHS/2000 was almost perfect, but not with
      SDM/2002. CONCLUSIONS: A high rate of overweight and obesity was found in this
      group of children with DS, independent of the charts used or their comorbidities.

PMID- 26204537
TI  - [Rates of frailty among older people ascribed to Chilean primary care clinics].
AB  - BACKGROUND: Frailty is not universal among older people but increases the risk of
      dependence. AIM: To assess frailty among older people and its relationship with
      biological, psychological and social factors. MATERIAL AND METHODS: Seven hundred
      fifty four older people aged 73 +/- 6 years (61% females), attending a public
      primary care were assessed. Frailty was defined according to Fried criteria that
      considers inexplicable weight loss, tiredness, muscle weakness and lack of
      physical activity. RESULTS: Absence of frailty, pre-frailty and frailty was found
      in 26, 69 and 5% of participants, respectively. Significant differences between
      frailty groups were observed for age, gender, years of studies, minimental and
      self-efficacy scores. Among participants defined as being in a pre-frail
      condition, 59% were non-disabled without risk and 41% non-disabled in risk,
      according to the functional assessment for older people used in Chilean primary
      care clinics. CONCLUSIONS: Frailty among older people is associated with
      increasing age, education, cognitive status and self-efficacy.

PMID- 26204538
TI  - [Respiratory day hospital care for immunocompetent adult patients with community
      acquired pneumonia].
AB  - BACKGROUND: Day hospitals can reduce health care costs without increasing the
      risks of patients with lower respiratory tract infection. AIM: To report the
      experience of a respiratory day hospital care delivered to adult patients with
      community-acquired pneumonia (CAP) in a public hospital. MATERIAL AND METHODS:
      During the fall and winter of 2011 and 2012, adult patients with CAP of
      intermediate risk categories were assessed in the emergency room, their severity
      was stratified according to confusion, respiratory rate, blood pressure, 65 years
      of age or older (CRB-65) score and the Chilean CAP Clinical Guidelines, and were
      admitted to the respiratory day hospital. RESULTS: One hundred seventeen patients
      aged 67 +/- 16 years, (62% females) with CAP were attended in the respiratory day
      hospital. Ninety percent had comorbidities, especially chronic obstructive
      pulmonary disease in 58%, heart disease in 32%, diabetes in 16% and asthma in
      13%. Their most important risk factors were age over 65 years in 60%,
      comorbidities in 88%, failure of antibiotic treatment in 17%, loss of autonomy in
      21%, vital sign abnormalities in 60%, mental confusion in 5%, multilobar CAP in
      23%, pleural effusion in 15%, hypoxemia in 41% and a serum urea nitrogen over 30
      mg/dL in 16%. Patients stayed an average of seven days in the day hospital with
      oxygen, hydration, chest physiotherapy and third-generation cephalosporins (89%)
      associated with quinolones (52%) or macrolides (4%). Thirteen patients required
      noninvasive ventilation, eight patients were hospitalized because of clinical
      deterioration and three died in hospital. CONCLUSIONS: Day hospital care reduced
      hospital admission rates of patients with lower respiratory tract infections.

PMID- 26204539
TI  - [Health and economic benefits of reducing 10 um particulate matter (PM10) in
      Metropolitan Area of Concepcion, Chile].
AB  - BACKGROUND: Several international studies show the effects of PM10 pollution on
      health but specific analyses for many cities in Chile are lacking. AIM: To relate
      PM10 concentrations to effects with population health and quantify the economic
      benefits of its reduction in Concepcion Metropolitan Area. MATERIAL AND METHODS:
      Poisson regression and generalized additive models were used to analyze the short
      term effects of PM10 on mortality and morbidity, controlling for lags, seasonal,
      trend and weather variables. The damage function method to determine the economic
      impact of pollution reduction was used. RESULTS: The selected concentration
      response (C-R) coefficients showed that PM10 concentrations had effects on
      hospital admissions with a two days lag for respiratory diseases in children
      under 15 years of age and with a one day lag for asthma in patients over 64
      years. The effects on premature mortality had a six days lag. The decrease in 1
      ug/m3 of PM10 concentration would generate benefits ranging from 1,025.8 to
      32,490.9 million of Chilean pesos per year, with a confidence level of 95%,
      according the estimation based on concentration-response coefficients and their
      economic cost. CONCLUSIONS: Reduction of PM10 would have important health and
      economic benefits.

PMID- 26204540
TI  - [Effects of gender and socioeconomic status of older people on the execution of
      the 6 minute walk test].
AB  - BACKGROUND: The six minute walk test (6MWT) is an important physical performance
      measure used in older people. AIM: To assess the total distance walked and the
      physiological cost of the 6MWT in non-disabled older people. MATERIAL AND
      METHODS: Fifty six females aged 69 +/- 5 years with a body mass index (BMI) of 31
      +/- 4 kg/m2 and sixteen males aged 70 +/- 7 years with a BIM of 29 +/- 4 kg/m2
      underwent a 6MWT. The total distance walked was registered and the physiological
      cost (PC) of the test was calculated as the ratio between the difference of heart
      rate at work and at rest and the walking speed. The socioeconomic status (SES) of
      participants was determined using a questionnaire designed in Chile. RESULTS:
      Among participants of middle-lower and middle-upper SES, the PC was 0.43 +/- 0.1
      and 0.44 +/- 0.09 beats/min, respectively, p = NS. Males of middle-upper SES had
      a significantly higher PC than their middle-lower SES counterparts. The total
      distance walked was 493 +/- 58 and 501 +/- 63 m among participants of upper and
      lower SES. The plateau in reserve heart rate appeared earlier among participants
      of upper SES of both genders. CONCLUSIONS: Older participants of middle-upper SES
      had a higher physiological efficiency during the execution of the 6MWT.

PMID- 26204541
TI  - [Conscientious objection in medical practice].
AB  - Medical practice implies the controversial encounter of diverse circumstances in
      which eventual conflicts between physicians and patients values as well as
      between physicians values and legal or institutional rules arise. When dealing
      with these situations, physicians have the right to refuse acting against their
      moral conscience. This conscientious objection, accepted as a personal right and
      recognized by several legislations and medical ethics codes, is valid only if it
      has been reasonably justified and declared in advance. Conversely, it would be
      invalid if it is based upon convenience or understood as a collective refusal,
      which may be a form of civil disobedience. Conscientious objection in medicine is
      considered a limited right even though patients ought to be respected in their
      demands for legally accepted treatments or interventions. On the other hand,
      personal conscientious objection is different from the prerogative of
      institutions to establish their own regulations according to their institutional
      ideology or ethics codes. However, public hospitals have to offer all treatments
      or interventions legally allowed, since the state has the obligation to guarantee
      all citizens an appropriate access to them. 

PMID- 26204542
TI  - [How to write a case report for publication. A practical guide].
AB  - This article provides a practical guide on how to write a case report and to try
      to publish it in a medical journal. With a teaching purpose intended for young
      physicians the author provides thoughts on the importance of communicating case
      studies for the progress of medicine, how to find out if the clinical case
      provides novelties and deserves to be published, how to conduct a literature
      search and how to handle it for drafting the manuscript, tips on how to write a
      case report, how to choose the journal in which to try to publish the manuscript,
      and some rules that should be followed to improve the chances of it being
      accepted and published. 

PMID- 26204543
TI  - [Suicide in hospitalized patients and medical liability].
AB  - Suicide is a complex phenomenon that has accompanied human beings throughout
      history. Its strong association with mental disorders led to its medicalization
      and psychiatrists became the physicians in charge of diagnosing and treating
      patients at risk of suicide. This article discusses the potential limitations
      that psychiatrists may face when diagnosing suicide risk and providing optimal
      care. Evidence of the eventual inevitability of suicide and the tension that may
      arise between providing optimal treatments on the one hand and preserving the
      rights of patient's autonomy and dignity on the other is also presented. We
      propose that although diagnosing and adequately treating patients at risk of
      suicide would be the psychiatrist's responsibility, the act of suicide itself is
      personal and non-transferable. Considering the latter as part of the medical
      team's responsibilities would turn working with patients with mental disorders
      into a fearless act. Finally, suicide should be considered to be part of the
      natural history of the evolution of many mental disorders and, thus, should
      constitute a specific topic when training specialists. 

PMID- 26204544
TI  - [Professional profiles of graduates from Chilean faculties of medicine].
AB  - BACKGROUND: The professional profile of health care professionals should
      incorporate recommendations of international agencies and adapt to the local
      conditions of each country. AIM: To conduct a qualitative analysis of Medical
      Graduate Profiles of universities grouped in the Chilean Association of Medicine
      Faculties (ASOFAMECH), characterizing its Social Focus, Humanist Approach, Social
      and Communication Skills. MATERIAL AND METHODS: Documentary analysis of profiles
      published on the respective web pages, using Atlas Ti software, establishing
      emerging categories and subcategories. These profiles were compared with the
      recommendations of the Pan-American Health Organization. RESULTS: Data in Social
      Focus suggests that although community issues are a common element, the work in
      primary health and health promotion are rarely included. The Humanist Approach is
      addressed more commonly than the Social Focus, emphasizing humanization of care,
      ethical and religious values. Although, social and communication skills are
      scarcely acknowledged, those mentioned are teamwork and leadership role.
      CONCLUSIONS: There is a marked heterogeneity in the information declared and
      universities have not fully incorporated the recommendations of international
      organizations.

PMID- 26204545
TI  - [Intracranial sinus venous thrombosis in ulcerative colitis. Report of one case].
AB  - Intracranial sinus venous thrombosis (ICSVT) is a rare complication of ulcerative
      colitis that affects from 1.7 to 7.5% of patients. We report a 22 year-old male
      with ulcerative colitis in treatment with mesalazine and prednisone presenting
      with headache and speech disturbances. A magnetic resonance imaging of the brain
      showed a left temporal hemorrhagic infarct with thrombosis of the ispilateral
      superficial vein and sigmoid venous sinus. No cause of thrombophilia was
      detected. Anticoagulation with heparin was started which was changed to oral
      anticoagulation with warfarin. The patient was discharged ten days after
      admission. 

PMID- 26204546
TI  - [Necrotizing tracheobronchial aspergillosis in an immunosuppressed patient.
      Report of one case].
AB  - Necrotizing tracheobronchitis due to Aspergillus spp is a rare form of invasive
      aspergillosis. This infection is limited to or predominant in the bronchial tree.
      The clinical evolution is gradual: from mild non-specific manifestations of acute
      tracheobronchitis to severe acute respiratory insufficiency determined by a
      bronchial obstruction syndrome. We report a 38 years old female with systemic
      lupus erythematosus treated with methylprednisolone and cyclophosphamide. She
      developed an invasive aspergillosis, severe respiratory failure with predominant
      tracheobronchial damage and upper respiratory complications. 

PMID- 26204548
TI  - [Calcium pyrophosphate dihydrate crystal deposition disease as an example of
      illness presentation in the elderly].
AB  - Illness presentation in the elderly may be entirely non-specific, with fatigue,
      loss of function or the presence of geriatric syndromes. We report a 90 years old
      male consulting in the emergency room for delirium that persisted throughout
      hospitalization without finding a cause. During the course of hospitalization
      mild fever appeared and a left knee swelling became apparent. A synovial fluid
      aspiration showed a leukocyte count of 360 per field with 60% polymorphonuclear
      cells. The culture was negative. With a presumptive diagnosis of pseudogout,
      cochicine and celecoxib were started with remission of the confusional state. The
      patient was discharged 13 days after admission in good conditions. 

PMID- 26204547
TI  - [Fecal microbiota transplantation in recurrent Clostridium difficile infection.
      Report of one case].
AB  - Fecal microbiota transplantation (FMT) has an incomparable efficacy to treat
      recurrent Clostridium difficile infection, with near 90% of success. We report a
      57 years old woman who developed an antibiotic associated diarrhea with a
      positive polymerase chain reaction test for Clostridium Difficile toxin. She was
      successfully treated with Vancomycin trice but diarrhea recurred. Therefore a
      fecal microbiota transplant was performed using solid stools from a relative,
      diluted in saline and instilled in the distal ileon, with a good clinical
      response, without recurrence of diarrhea, during a 6-month follow-up. 

PMID- 26204549
TI  - [Perception of newly graduated physicians on clinical skills acquired in medical
      schools in Lima, Peru].

PMID- 26204550
TI  - [Carrion's disease: the role of popular medicine in a unifying theory].

PMID- 26204552
TI  - [Correction].

PMID- 26204553
TI  - An anatomic and morphometric analysis of splenic variability using 3D
      reconstruction and spatial orientation from computed tomography.
AB  - INTRODUCTION: In terms of frequency, the spleen is the first organ affected in
      abdominal trauma, resulting even today in a high rate of mortality (10%).
      Nevertheless, very few studies have investigated splenic quantitative morphometry
      as to shape and spatial orientation. Therefore, we analysed healthy spleen
      variability in order to integrate it in its environment and to correlate its
      morphometric parameters to anthropometric characteristics. METHODS: Ninety
      abdominopelvic CT-scans performed on patients over 16 years with no splenic
      pathology were retrospectively selected among a Mediterranean population. Three
      age groups ([16-30], [30-60] and [over 60 years]), equally distributed among
      genders, were created. Parameters, such as volume, characteristic checkpoints,
      orientation, and morphology, were measured on the spleen, the 11th thoracic
      vertebra and the 10th ribs in three-dimensional reconstructions. Anthropometric
      parameters were characterised by waist circumference, costo-xiphoid angle,
      abdominal height and chest depth. RESULTS: Observed variations in splenic
      morphology were divided into three groups: cupped (66.7%), coiled (17.8%), and
      flat (15.5%). Splenic morphometry tends to be abdominal-shaped (54.5%) or dorsal
      shaped (45.5%). The mean of the angle between the main axis of the spleen and the
      CT-scan horizontal axis was 40+/-14 degrees . Correlations were highlighted
      between volume and gender (p<0.05), splenic morphology and liver morphometry
      (p<0.05) as well as between orientation of hilar surface and splenic morphometry
      (p<0.01). Moreover, the spleen is more horizontal in women (p<0.05), in the
      elderly (p<0.05) and in the obese (p<0.01). CONCLUSION: This study defines three
      groups based on shape and highlights correlations between parameters describing
      healthy splenic variability and its anthropometric characteristics, which are of
      great importance for numerical modelling in splenic studies.

PMID- 26204554
TI  - Prostanoids in Asthma and COPD: Actions, Dysregulation, and Therapeutic
      Opportunities.
AB  - Pathophysiologic gaps in the actions of currently available treatments for asthma
      and COPD include neutrophilic inflammation, airway remodeling, and alveolar
      destruction. All of these processes can be modulated by cyclic adenosine
      monophosphate-elevating prostaglandins E2 and I2 (also known as prostacyclin).
      These prostanoids have long been known to elicit bronchodilation and to protect
      against bronchoconstriction provoked by a variety of stimuli. Much less well
      known is their capacity to inhibit inflammatory responses involving activation of
      lymphocytes, eosinophils, and neutrophils, as well as to attenuate epithelial
      injury and mesenchymal cell activation. This profile of actions identifies
      prostanoids as attractive candidates for exogenous administration in asthma. By
      contrast, excessive prostanoid production and signaling might contribute to both
      the increased susceptibility to infections that drive COPD exacerbations and the
      inadequate alveolar repair that characterizes emphysema. Inhibition of endogenous
      prostanoid synthesis or signaling, thus, has therapeutic potential for these
      types of patients. By virtue of their pleiotropic capacity to modulate numerous
      pathophysiologic processes relevant to the expression and natural history of
      airway diseases, prostanoids emerge as attractive targets for therapeutic
      manipulation.

PMID- 26204556
TI  - Estimation of divergence times in litostomatean ciliates (Ciliophora:
      Intramacronucleata), using Bayesian relaxed clock and 18S rRNA gene.
AB  - The class Litostomatea comprises a diverse assemblage of free-living and
      endosymbiotic ciliates. To understand diversification dynamic of litostomateans,
      divergence times of their main groups were estimated with the Bayesian molecular
      dating, a technique allowing relaxation of molecular clock and incorporation of
      flexible calibration points. The class Litostomatea very likely emerged during
      the Cryogenian around 680 Mya. The origin of the subclass Rhynchostomatia is
      dated to about 415 Mya, while that of the subclass Haptoria to about 654 Mya. The
      order Pleurostomatida, emerging about 556 Mya, was recognized as the oldest group
      within the subclass Haptoria. The order Spathidiida appeared in the Paleozoic
      about 442 Mya. The three remaining haptorian orders evolved in the
      Paleozoic/Mesozoic periods: Didiniida about 419 Mya, Lacrymariida about 269 Mya,
      and Haptorida about 194 Mya. The subclass Trichostomatia originated from a
      spathidiid ancestor in the Mesozoic about 260 Mya. A further goal of this study
      was to investigate the impact of various settings on posterior divergence time
      estimates. The root placement and tree topology as well as the priors of the rate
      drift model, birth-death process and nucleotide substitution rate, had no
      significant effect on calculation of posterior divergence time estimates.
      However, removal of calibration points could significantly change time estimates
      at some nodes.

PMID- 26204557
TI  - Huygens synchronization of two clocks.
AB  - The synchronization of two pendulum clocks hanging from a wall was first observed
      by Huygens during the XVII century. This type of synchronization is observed in
      other areas, and is fundamentally different from the problem of two clocks
      hanging from a moveable base. We present a model explaining the phase opposition
      synchronization of two pendulum clocks in those conditions. The predicted
      behaviour is observed experimentally, validating the model. 

PMID- 26204555
TI  - Social Representations and Practices Towards Triatomines and Chagas Disease in
      Calakmul, Mexico.
AB  - Vector-borne transmission of Trypanosoma cruzi (VBTTc) is dependent on the
      concomitant interaction between biological and environmental hazard over the
      entire landscape, and human vulnerability. Representations and practices of
      health-disease-care-seeking and territorial appropriation and use were analyzed
      for VBTTc in a qualitative ethnographic study in the Zoh-Laguna landscape,
      Campeche, Mexico. In-depth interviews and participatory observation explored
      representations and practices regarding ethno-ecological knowledge related to
      vector-transmission, health-disease-care-seeking, and land use processes. The
      population has a broad knowledge of biting insects, which they believe are all
      most abundant in the rainy season; the community's proximity to natural areas is
      perceived as a barrier to control their abundance. Triatomines are mostly
      recognized by men, who have detailed knowledge regarding their occurrence and
      association with mammals in non-domestic fragments, where they report being
      bitten. Women emphasize the dermal consequences of triatomine bites, but have
      little knowledge about the disease. Triatomine bites and the chinchoma are
      "normalized" events which are treated using home remedies, if at all. The
      neglected condition of Chagas disease in Mexican public health policies,
      livelihoods which are dependent on primary production, and gender-related
      knowledge (or lack thereof) are structural circumstances which influence the
      environment and inhabitants' living conditions; in turn, these trigger triatomine
      human contact. The most important landscape practices producing vulnerability are
      the activities and mobility within and between landscape fragments causing
      greater exposure of inhabitants primarily in the dry season. A landscape approach
      to understanding vulnerability components of VBTTc from health-disease-care
      seeking perspectives and based on territorial appropriation and use, is essential
      where there is continuous movement of vectors between and within all habitats. An
      understanding of the structural factors which motivate the population's
      perceptions, beliefs, and practices and which create and maintain vulnerability
      is essential to develop culturally relevant and sustainable community-based VBTTc
      prevention and control. 

PMID- 26204558
TI  - Prevalence and Patient-Level Risk Factors for 30-Day Readmissions Following Free
      Tissue Transfer for Head and Neck Cancer.
AB  - IMPORTANCE: Hospital readmissions are a marker of surgical care delivery and
      quality that are progressively more scrutinized. OBJECTIVE: To provide a
      comprehensive analysis of 30-day readmissions for patients with head and neck
      cancer who underwent free flap reconstruction to highlight the rate, causes, and
      associated patient risk factors. DESIGN, SETTING, AND PARTICIPANTS: Retrospective
      cohort study at a single tertiary care academic institution. The study consisted
      of 249 patients who underwent microvascular reconstruction of a presumed head and
      neck oncologic defect from January 1, 2000, through June 30, 2014. Follow-up
      continued through July 30, 2014. INTERVENTIONS: Microvascular reconstruction of
      an oncologic head and neck defect. MAIN OUTCOMES AND MEASURES: Incidence of 30
      day all-cause readmissions, patient risk factors, and readmission indications.
      Regression analyses were conducted to discern patient-level risk factors related
      to 30-day readmissions. RESULTS: Among the 249 patients, the 30-day all-cause
      readmission rate was 14.5%, while the unplanned readmission rate was 11.6%. The
      most common reason for readmission was neck wound complications. Predictors of
      readmission following multivariable analysis were T4 pathologic stage (odds ratio
      [OR], 11.68; 95% CI, 1.37-99.81; P = .02) and having a tumor located in the
      oropharynx (OR, 4.64; 95% CI, 1.89-11.38; P = .001), hypopharynx (OR, 8.30; 95%
      CI, 1.52-45.24; P = .01), or larynx (OR, 10.97; 95% CI, 2.27-52.98; P = .003).
      Patients who were readmitted were more likely to experience neck wound
      complications (OR, 5.07; 95% CI, 1.31-19.57; P = .02) and undergo reoperation
      (OR, 47.20; 95% CI, 8.33-267.33; P < .001). CONCLUSIONS AND RELEVANCE: In this
      study, advanced pathologic tumor staging and tumor location were associated with
      30-day readmissions in patients with head and neck cancer who receive free flaps.
      Our results provide a benchmark for risk stratification that can be used in
      system-based practice improvements, health care cost savings, and postoperative
      patient counseling.

PMID- 26204559
TI  - Relationships among the structural topology, bond strength, and mechanical
      properties of single-walled aluminosilicate nanotubes.
AB  - Carbon nanotubes (CNTs) are regarded as small but strong due to their nanoscale
      microstructure and high mechanical strength (Young's modulus exceeds 1000 GPa). A
      longstanding question has been whether there exist other nanotube materials with
      mechanical properties as good as those of CNTs. In this study, we investigated
      the mechanical properties of single-walled aluminosilicate nanotubes (AlSiNTs)
      using a multiscale computational method and then conducted a comparison with
      single-walled carbon nanotubes (SWCNTs). By comparing the potential energy
      estimated from molecular and macroscopic material mechanics, we were able to
      model the chemical bonds as beam elements for the nanoscale continuum modeling.
      This method allowed for simulated mechanical tests (tensile, bending, and
      torsion) with minimum computational resources for deducing their Young's modulus
      and shear modulus. The proposed approach also enabled the creation of
      hypothetical nanotubes to elucidate the relative contributions of bond strength
      and nanotube structural topology to overall nanotube mechanical strength. Our
      results indicated that it is the structural topology rather than bond strength
      that dominates the mechanical properties of the nanotubes. Finally, we
      investigated the relationship between the structural topology and the mechanical
      properties by analyzing the von Mises stress distribution in the nanotubes. The
      proposed methodology proved effective in rationalizing differences in the
      mechanical properties of AlSiNTs and SWCNTs. Furthermore, this approach could be
      applied to the exploration of new high-strength nanotube materials. 

PMID- 26204560
TI  - Comparing time and risk preferences across three post-industrial UK cities.
AB  - Time and risk preferences are known to vary considerably across individuals but
      less is known about the determinants of these individual differences. This paper
      examines whether preferences vary by geographical location. The motivation for
      examining geographic heterogeneity is the higher level of mortality experienced
      in Glasgow over and above that explained by deprivation, sometimes referred to as
      the 'Glasgow effect'. Data were collected from 3702 individuals across Glasgow,
      Manchester and Liverpool between July and November 2011. The results show
      evidence of geographic preference heterogeneity. Contrary to our hypothesis,
      individuals in Glasgow have a lower rather than higher time preference rate.
      Individuals in Glasgow are on average more risk seeking compared to Liverpool and
      more likely to be at the tail end of the distribution (very risk seeking)
      compared to Manchester. Differences in risk preferences may help explain some of
      the differences in mortality associated with risky health behaviours such as drug
      and alcohol use. However, individuals in Glasgow were also more future oriented
      suggesting that they are less likely to engage in risky healthy behaviours. As
      the differences in time and risk preferences work in opposite directions in terms
      of health investments it less likely that these differences can help explain
      excess mortality in Glasgow. 

PMID- 26204561
TI  - A closer look at the rural-urban health disparities: Insights from four major
      diseases in the Commonwealth of Virginia.
AB  - Health disparities are increasingly recorded in literature, but are much less
      understood in a rural-urban context. This study help bridges this gap through
      investigation of four major diseases in the Commonwealth of Virginia: cancer,
      stroke, cardiovascular disease and chronic obstructive pulmonary disease. We
      utilize a unique inpatient hospital discharge billing dataset, and construct
      average patient counts at ZIP-code level over 2006-2008 where covariates from
      alternative sources are merged (806 ZIP-code areas, 190 urban, 616 rural). Count
      data regressions are first fitted to identify possible regional-level factors
      that affect disease incidences. A system of equations with rural-urban
      specification are then estimated via seemingly unrelated regression techniques to
      account for possible associations among these diseases and correlations of
      errors, which is followed by disease-specific nonlinear Blinder-Oaxaca
      decompositions that compare the respective explanatory powers of observed
      characteristics and unobserved mechanisms. Results suggest that regional-level
      factors are significantly correlated with health outcomes in both rural and urban
      areas. The unknown mechanisms behind these linkages are different between rural
      and urban areas, and explain even larger proportions of the observed disparities.
      These findings confirm the role of regional-level factors in generating rural
      urban health disparities, and call for further investigations of the causal
      mechanisms of such disparities that remain largely unknown. 

PMID- 26204562
TI  - Constraints on soluble aerosol iron flux to the Southern Ocean at the Last
      Glacial Maximum.
AB  - Relief of iron (Fe) limitation in the Southern Ocean during ice ages, with
      potentially increased carbon storage in the ocean, has been invoked as one driver
      of glacial-interglacial atmospheric CO2 cycles. Ice and marine sediment records
      demonstrate that atmospheric dust supply to the oceans increased by up to an
      order of magnitude during glacial intervals. However, poor constraints on soluble
      atmospheric Fe fluxes to the oceans limit assessment of the role of Fe in glacial
      interglacial change. Here, using novel techniques, we present estimates of water-
      and seawater-soluble Fe solubility in Last Glacial Maximum (LGM) atmospheric dust
      from the European Project for Ice Coring in Antarctica (EPICA) Dome C and Berkner
      Island ice cores. Fe solubility was very variable (1-42%) during the interval,
      and frequently higher than typically assumed by models. Soluble aerosol Fe fluxes
      to Dome C at the LGM (0.01-0.84 mg m(-2) per year) suggest that soluble Fe
      deposition to the Southern Ocean would have been >=10 * modern deposition,
      rivalling upwelling supply. 

PMID- 26204563
TI  - Reconstruction of the Lateral Mandibular Defect: A Review and Treatment
      Algorithm.
AB  - Reconstruction of the lateral mandibular defect presents a complex challenge to
      the reconstructive surgeon, often involving interconnected soft-tissue and bone
      requirements. This review examines the current literature on functional outcomes
      of lateral mandibular reconstruction and presents an algorithm on selecting an
      optimal reconstructive choice for patients with lateral mandibular defects
      resulting from oncologic ablative surgery or trauma. PubMed and Medline searches
      on reconstructing lateral mandibular defect were performed of the English
      literature. Search terms included lateral mandibular defect, outcomes of
      mandibular reconstruction, and free flap reconstruction of mandible. Although
      most of the articles presented are retrospective reviews, priority was given to
      the articles with high-quality level of evidence. Restoration of function,
      including speech and swallow, and acceptable cosmetic result are the primary
      objectives of lateral mandibular reconstruction. When reconstructing the mandible
      in a patient following tumor extirpation, the patient's overall prognosis,
      medical comorbidities, and need for adjuvant therapy should be considered. In the
      patient with aggressive malignant disease and a poor prognosis, a less complex
      reconstruction, such as soft-tissue flap with or without a reconstruction plate,
      may be adequate. In a dentate patient with favorable prognosis, a durable
      reconstruction, such as osseocutaneous microvascular free flap, is often
      preferred. Various reconstructive options are available for patients with lateral
      mandibular defects. Depending on the predominance of the soft-tissue or bony
      components of the defect, with consideration of the patient's characteristics and
      functional and aesthetic goals, the surgeon can wisely select from these
      reconstructive possibilities. 

PMID- 26204564
TI  - CVD synthesis of Mo((1-x))W(x)S2 and MoS(2(1-x))Se(2x) alloy monolayers aimed at
      tuning the bandgap of molybdenum disulfide.
AB  - As a rising star in two-dimensional (2D) layered materials, transition metal
      dichalcogenides (TMDs) have attracted tremendous attention for their potential
      applications in nanoelectronics, optoelectronics and photonics. Driven by the
      high standards of practical devices, alloying theory has been proposed for
      modulating the electronic structure of TMDs materials as well as their physical
      and chemical properties. To date, however, very limited alloy materials can be
      synthesized by chemical vapor deposition (CVD) and a very limited band gap range
      can be achieved. Herein, for the first time, we report a one-step CVD strategy
      for the growth of ternary alloy Mo(1-x)WxS2 monolayers (ML) on SiO2/Si substrates
      with controllable composition. Both Mo(1-x)WxS2 and MoS2(1-x)Se2x alloy materials
      with high crystallinity were synthesized in this study. Therefore, the bandgap
      photoluminescence (PL) can be broaden from 1.97 eV (for ML-WS2) to 1.55 eV (for
      ML-MoSe2). Furthermore, density functional theory calculations were performed to
      reveal the important role of alloying in tailoring the electronic structure of 2D
      materials. 

PMID- 26204565
TI  - Balancing awareness: Vestibular signals modulate visual consciousness in the
      absence of awareness.
AB  - The processing of visual and vestibular information is crucial for perceiving
      self-motion. Visual cues, such as optic flow, have been shown to induce and alter
      vestibular percepts, yet the role of vestibular information in shaping visual
      awareness remains unclear. Here we investigated if vestibular signals influence
      the access to awareness of invisible visual signals. Using natural vestibular
      stimulation (passive yaw rotations) on a vestibular self-motion platform, and
      optic flow masked through continuous flash suppression (CFS) we tested if
      congruent visual-vestibular information would break interocular suppression more
      rapidly than incongruent information. We found that when the unseen optic flow
      was congruent with the vestibular signals perceptual suppression as quantified
      with the CFS paradigm was broken more rapidly than when it was incongruent. We
      argue that vestibular signals impact the formation of visual awareness through
      enhanced access to awareness for congruent multisensory stimulation. 

PMID- 26204566
TI  - Transcranial direct current stimulation of the motor cortex in waking resting
      state induces motor imagery.
AB  - This study investigates if anodal and cathodal transcranial direct current
      stimulation (tDCS) of areas above the motor cortex (C3) influences spontaneous
      motor imagery experienced in the waking resting state. A randomized triple
      blinded design was used, combining neurophysiological techniques with tools of
      quantitative mentation report analysis from cognitive linguistics. The results
      indicate that while spontaneous motor imagery rarely occurs under sham
      stimulation, general and athletic motor imagery (classified as athletic
      disciplines), is induced by anodal tDCS. This insight may have implications
      beyond basic consciousness research. Motor imagery and corresponding motor
      cortical activation have been shown to benefit later motor performance.
      Electrophysiological manipulations of motor imagery could in the long run be used
      for rehabilitative tDCS protocols benefitting temporarily immobile clinical
      patients who cannot perform specific motor imagery tasks - such as dementia
      patients, infants with developmental and motor disorders, and coma patients. 

PMID- 26204567
TI  - Changes in negative implicit evaluations in patients of hypochondriasis after
      treatment with cognitive therapy or exposure therapy.
AB  - BACKGROUND AND OBJECTIVES: Previous studies using modified versions of the Affect
      Misattribution Procedure (AMP; Payne, Cheng, Govorun, & Stewart, 2005) have
      revealed that there is an implicit negative evaluation bias of illness-related
      information in patients with hypochondriasis (HYP), which might be a maintaining
      feature of HYP. However, there is no evidence on whether this bias might be
      targeted successfully by effective treatments, such as exposure therapy (ET) or
      cognitive therapy (CT). This is the first study to examine the change in negative
      implicit evaluations in a randomized controlled trial, including individual CT
      and ET, compared to a wait-list control group for HYP. METHODS: An AMP with
      illness, symptom and neutral primes was used in 70 patients with HYP before and
      after treatment (wait-list respectively). RESULTS: There was no significant
      change in negative implicit affective evaluations in both CT and ET, compared to
      wait-list. However, comparisons between the two active treatments revealed an
      interaction effect, that only for CT were the affective reactions on illness-as
      well as symptom-related prime trials (but not neutral primes) significantly more
      positive at post-compared to pre-treatment. In CT but not in ET, the reduction of
      implicit negative evaluation bias regarding symptom-related primes was
      significantly related to the reduction of self-reported health anxiety.
      LIMITATIONS: The small subsample sizes for CT and ET, in comparison to wait-list,
      prohibit the detection of smaller effects. CONCLUSIONS: Formal cognitive
      restructuring is necessary for reducing implicit negative evaluation bias in HYP,
      but the latter is not a prerequisite for reducing health anxiety. Thus, the
      importance of the negative implicit evaluation bias for the maintenance of HYP
      remains questionable.

PMID- 26204568
TI  - Analysis of associations between congenital heart defect complexity and health
      related quality of life using a meta-analytic strategy.
AB  - BACKGROUND: As a consequence of heterogeneous results of relatively small
      individual trials, the impact of congenital heart defects (CHD) and the effect of
      disease severity on patient reported outcome measures (PROs) of quality of life
      (QoL) remains uncertain. We aimed to systematically summarize QoL data in CHD
      patients using meta-analytic methods. METHODS AND RESULTS: We performed a
      systematic review of the literature focusing on QoL in CHD. The search yielded
      234 publications meeting the inclusion criteria, with a median of 88 patients per
      study (46% females, average age 24years). In total, QoL was reported using PROs
      in 47,471 CHD-patients. More than 95 different PROs were used to evaluate QoL.
      The most commonly used tool was the SF36 form (69 publications). Analysis of
      available quantitative QoL data from SF36 publications (n=4217 CHD patients)
      showed that QoL was reduced in patients with moderate or complex cardiac disease
      (e.g. relative physical functioning scores 0.96 [0.93-0.99] and 0.91 [0.88-0.95]
      compared with controls), while no such effect was evident in those patients with
      simple cardiac lesions. Similar results were found for the general health domain
      of the SF36 domain. CONCLUSIONS: Despite the proliferation of QoL-studies in CHD
      no standardized approach for measuring and reporting QoL has emerged and the
      published results are heterogeneous. In aggregation, however, the results of this
      study suggest that QoL is impaired in moderate or complex CHD, while no such
      impact of CHD on QoL could be established--on average--in patients with simple
      defects.

PMID- 26204569
TI  - Increasing HDL levels by inhibiting cholesteryl ester transfer protein activity
      in rabbits with hindlimb ischemia is associated with increased angiogenesis.
AB  - BACKGROUND: High density lipoprotein (HDL) infusions increase new blood vessel
      formation (angiogenesis) in rodents with ischemic injury. This study asks if
      increasing HDL levels by inhibiting cholesteryl ester transfer protein (CETP)
      activity increases angiogenesis in New Zealand White (NZW) rabbits with hindlimb
      ischemia. METHODS AND RESULTS: NZW rabbits were maintained for 6weeks on chow or
      chow supplemented with 0.07% or 0.14% (wt/wt) of the CETP inhibitor, des-fluoro
      anacetrapib. The left femoral artery was ligated after 2weeks of des-fluoro
      anacetrapib treatment. The animals were sacrificed 4weeks after femoral artery
      ligation. Treatment with 0.07% and 0.14% (wt/wt) des-fluoro-anacetrapib reduced
      CETP activity by 63+/-12% and 81+/-8.6%, increased plasma apoA-I levels by 1.3+/
      0.1- and 1.4+/-0.1-fold, and increased plasma HDL-cholesterol levels by 1.4+/-0.1
      and 1.7+/-0.2-fold, respectively. Treatment with 0.07% and 0.14% (wt/wt) des
      fluoro-anacetrapib increased the number of collateral arteries by 60+/-16% and
      84+/-27%, and arteriole wall area in the ischemic hindlimbs by 84+/-16% and 94+/
      13%, respectively. Capillary density in the ischemic hindlimb adductor muscle
      increased from 1.1+/-0.2 (control) to 2.1+/-0.3 and 2.2+/-0.4 in the 0.07% and
      0.14% (wt/wt) des-fluoro-anacetrapib-treated animals, respectively. Incubation of
      HDLs from des-fluoro-anacetrapib-treated animals with human coronary artery
      endothelial cells at apoA-I concentrations comparable with their plasma levels
      increased tubule network formation. These effects were abolished by knockdown of
      scavenger receptor-B1 (SR-B1) and PDZK1, and pharmacological inhibition of
      PI3K/Akt. CONCLUSION: Increasing HDL levels by inhibiting CETP activity is
      associated with increased collateral blood vessel formation in NZW rabbits with
      hindlimb ischemia in an SR-B1- and PI3K/Akt-dependent manner.

PMID- 26204570
TI  - The effect of varying the number of contributors on likelihood ratios for complex
      DNA mixtures.
AB  - Interpretation of DNA mixtures with three or more contributors, defined here as
      high order mixtures, is difficult because of the inevitability of allele sharing.
      Allele sharing complicates the estimation of the number of contributors, which is
      an important parameter to assess the probative value. Consequently, these
      mixtures may not be deemed suitable for interpretation and reporting. In this
      study, we generated three-, four- and five-person mixtures with little or no drop
      out and with varying levels of allele sharing. For these DNA mixtures we computed
      likelihood ratios (LRs) using the LRmix model, and always using persons of
      interest that are true contributors. We assessed the influence of different
      scenarios on the LR, and used (1) the true or an incorrect number of
      contributors, (2) zero, one or two anchored individuals and (3) an equal number
      of contributors under Hp and Hd or an extra contributor under Hd. It was shown
      that the LR varied considerably when the hypotheses used an incorrect number of
      contributors, especially when individuals were anchored under the hypotheses.
      Overall, when analysing high order mixtures, there may occur a transition from LR
      greater than one to less than one if an incorrect number of contributors is
      conditioned. This is a result of allele sharing among the multiple contributors
      rather than allele drop-out, since this study only utilised samples with little
      or no drop-out. 

PMID- 26204572
TI  - Chronic bisphenol A exposure alters behaviors of zebrafish (Danio rerio).
AB  - The adult zebrafish (Danio rerio) were exposed to treated-effluent concentration
      of bisphenol A (BPA) or 17beta-estradiol (E2) for 6 months to evaluate their
      effects on behavioral characteristics: motor behavior, aggression, group
      preference, novel tank test and light/dark preference. E2 exposure evidently
      dampened fish locomotor activity, while BPA exposure had no marked effect.
      Interestingly, BPA-exposed fish reduced their aggressive behavior compared with
      control or E2. Both BPA and E2 exposure induced a significant decrease in group
      preference, as well as a weaker adaptability to new environment, exhibiting lower
      latency to reach the top, more entries to the top, longer time spent in the top,
      fewer frequent freezing, and fewer erratic movements. Furthermore, the circadian
      rhythmicity of light/dark preference was altered by either BPA or E2 exposure.
      Our results suggest that chronic exposure of treated-effluent concentration BPA
      or E2 induced various behavioral anomalies in adult fish and enhanced ecological
      risk to wildlife. 

PMID- 26204571
TI  - Type 2 responses at the interface between immunity and fat metabolism.
AB  - Adipose tissue resident leukocytes are often cast solely as the effectors of
      obesity and its attendant pathologies; however, recent observations have
      demonstrated that these cells support and effect 'healthy' physiologic function
      as well as pathologic dysfunction. Importantly, these two disparate outcomes are
      underpinned by similarly disparate immune programs; type 2 responses instruct and
      promote metabolic normalcy, while type 1 responses drive tissue dysfunction. In
      this Review, we summarize the literature regarding type 2 immunity's role in
      adipose tissue physiology and allude to its potential therapeutic implications. 

PMID- 26204573
TI  - Concentration and chiral signature of chlordane in soils and sediments of the
      Central Tibetan Plateau, China: Transformation in the surficial process.
AB  - The fraction of trans-chlordane (TC) in chlordane was used to indicate racemic
      degradation while the enantiomer fractions (EFs) indicated enantioselective
      depletion. In 44 soils of the Central Tibetan Plateau, the fractions of TC ranged
      from 0.368 to 0.411. The EFs ranged from 0.174 to 0.696 for TC and from 0.483 to
      0.672 for cis-chlordane (CC). (-) enantiomer excess (ee) was found to be 80.0% in
      the soils for TC and (+) ee was 86.5% for CC. The fraction of TC changed with the
      clay content while the EFs changed with the soil organic carbon. Meanwhile, the
      fractions of TC and the EFs were determined for the surficial sediments in
      Yamzhog Yumco Lake, which were compared with those in the soils at its catchment
      area. The composition and chiral signature of chlordane did not vary between
      soils and sediments. Our results will help to elucidate the transformation of
      chlordane in soils and in surficial transport. 

PMID- 26204574
TI  - Bioethics and the Right to Health: Advancing a Complementary Agenda.
AB  - This special section in Health and Human Rights Journal explores the relationship
      between bioethics and the right to health. Although bioethics scholars may argue
      for a right to health, particularly in the domains of universal health coverage
      and global health governance, and human rights scholars may advance ethical norms
      in their work, there has been little scholarly attention to the intersections,
      synergies, and contrasts between these two areas of study. At first glance, this
      is surprising given that bioethics and human rights share conceptual and
      normative terrain in articulating guidance for action on health-related issues
      and international policy and practice is explicitly interrelating human rights
      and ethics. 

PMID- 26204575
TI  - Conflicting Rights: How the Prohibition of Human Trafficking and Sexual
      Exploitation Infringes the Right to Health of Female Sex Workers in Phnom Penh,
      Cambodia.
AB  - While repressive laws and policies in relation to sex work have the potential to
      undermine HIV prevention efforts, empirical research on their interface has been
      lacking. In 2008, Cambodia introduced antitrafficking legislation ostensibly
      designed to suppress human trafficking and sexual exploitation. Based on
      empirical research with female sex workers, this article examines the impact of
      the new law on vulnerability to HIV and other adverse health outcomes. Following
      the introduction of the law, sex workers reported being displaced to streets and
      guesthouses, impacting their ability to negotiate safe sex and increasing
      exposure to violence. Disruption of peer networks and associated mobility also
      reduced access to outreach, condoms, and health care. Our results are consistent
      with a growing body of research which associates the violation of sex workers'
      human rights with adverse public health outcomes. Despite the successes of the
      last decade, Cambodia's AIDS epidemic remains volatile and the current legal
      environment has the potential to undermine prevention efforts by promoting stigma
      and discrimination, impeding prevention uptake and coverage, and increasing
      infections. Legal and policy responses which seek to protect the rights of the
      sexually exploited should not infringe the right to health of sex workers. 

PMID- 26204576
TI  - Focusing on Prevention: The Social and Economic Rights of Children Vulnerable to
      Sex Trafficking.
AB  - The commercial sexual exploitation of children ("CSEC") is an egregious human
      rights and public health violation that occurs every day across the US. Although
      there has been positive change in the US to bring attention to CSEC and to reform
      laws and policies to assist CSEC victims, scant attention and resources have been
      dedicated to prevention efforts. This paper critiques current US strategies to
      address CSEC and highlights the limitations of an interventionist framework that
      narrows its focus to anti-trafficking efforts. As an alternative, the paper
      proposes a human rights-based approach focusing on the fulfillment of economic
      and social rights of children as a prevention strategy in the U.S.

PMID- 26204577
TI  - Data-Driven Human Rights: Using Dual Loyalty Trainings to Promote the Care of
      Vulnerable Patients in Jail.
AB  - Dual loyalty is an omnipresent feature of correctional health. As part of a human
      rights quality improvement committee, and utilizing the unique advantage of a
      fully integrated electronic health record system, we undertook an assessment of
      dual loyalty in the New York City jail system. The evaluation revealed
      significant concerns about the extent to which the mental health service is
      involved in assessments that are part of the punishment process of the security
      apparatus. As a result, dual loyalty training was developed and delivered to all
      types of health staff in the jail system via anonymous survey. Six clinical
      scenarios were presented in this training and staff members were asked to
      indicate whether they had encountered similar circumstances and how they would
      respond. Staff responses to the survey raised concerns about the frequency with
      which they are pressured or asked to put aside their primary goal of patient care
      for the interests of the security mission. The online training and follow-up
      small group sessions have revealed widespread support for more training on dual
      loyalty. 

PMID- 26204578
TI  - Reproductive Rights or Reproductive Justice? Lessons from Argentina.
AB  - Argentine sexual and reproductive rights activists insist on using the language
      and framework of "human rights," even when many reproductive rights activists in
      the US and elsewhere now prefer the framework of "reproductive justice."
      Reflecting on conversations with Argentine feminist anthropologists, social
      scientists, and reproductive rights activists, this paper analyzes why the
      Argentine movement to legalize abortion relies on the contested concept of human
      rights. Its conclusion that "women's rights are human rights" is a powerful claim
      in post-dictatorship politics where abortion is not yet legal and the full scope
      of women's rights has yet to be included in the government's human rights agenda.
      Argentine feminist human rights activists have long been attentive to the ways
      that social class, gender, migration, and racism intersect with reproduction.
      Because their government respects and responds to a human rights framework,
      however, they have not felt it necessary--as U.S. feminists have--to invent a new
      notion of reproductive justice in order to be heard. Given the increasing
      popularity of reproductive justice in health and human rights, the Argentine case
      shows that rights-based claims can still be politically useful when a State
      values the concept of human rights.

PMID- 26204579
TI  - The Right to Life in Peace: An Essential Condition for Realizing the Right to
      Health.
AB  - Since 2008, the UN Human Rights Council has been working on a declaration related
      to the right to peace. The Council has established an Open-Ended Working Group,
      which is refining the draft declaration. This paper discusses the relationship
      between the right to health and the right to life in peace; we argue that peace
      and the conditions that support peace are essential to realize the right to
      health. Health professionals have an important role to play in promoting the
      right to a life in peace. We suggest that human dignity, as foundational to all
      human rights as well as health professionals' codes of ethics, provides a
      normative basis for the progressive realization of both the rights to health and
      to life in peace. 

PMID- 26204580
TI  - A Sensitive Period: Bioethics, Human Rights, and Child Development.
AB  - This paper explores complementarities between bioethics and human rights in the
      ethical analysis of early childhood development (ECD) policies. It is argued that
      conceptual synergies arising from the integration of these fields are
      considerable, if underexplored, and best illumined through application to
      specific domains of health policy. ECD represents an especially germane case
      study: it is characterized by rapidly evolving science whose normative
      implications are complex, emergent, and understudied, yet whose societal impacts
      are wide-ranging. The paper first charts the disciplinary evolution of bioethics,
      demonstrating its gradual social turn: from the individual to collective, from
      the medical to the societal. It then reviews points of theoretical confluence
      between bioethics and human rights, to assess the value and feasibility of their
      joint application to health policy analysis. Finally, it maps these
      complementarities onto issues provoked by the epigenetics of ECD, in the hopes
      that both the policy domain and the analysis of theoretical synergies are
      enriched. It finds that the distinctly relational and emergent nature of ECD
      science and policy demands novel forms of normative inquiry. Only an ethical
      approach supple enough to adapt to emergent questions, examine issues from varied
      theoretical perspectives, and assimilate insights across traditional disciplinary
      bounds will prove sufficient to the task. 

PMID- 26204581
TI  - Setting a Minimum Standard of Care in Clinical Trials: Human Rights and Bioethics
      as Complementary Frameworks.
AB  - For the past few decades, there has been intense debate in bioethics about the
      standard of care that should be provided in clinical trials conducted in
      developing countries. Some interpret the Declaration of Helsinki to mean that
      control groups should receive the best intervention available worldwide, while
      others interpret this and other international guidelines to mean the best local
      standard of care. Questions of justice are particularly relevant where limited
      resources mean that the local standard of care is no care at all. Introducing
      human rights law into this complex and longstanding debate adds a new and
      important perspective. Through non-derogable rights, including the core
      obligations of the right to health, human rights law can help set a minimum
      standard of care. 

PMID- 26204582
TI  - Bioethics, Human Rights, and Childbirth.
AB  - The global reproductive justice community has turned its attention to the abuse
      and disrespect that many women suffer during facility-based childbirth. In 2014,
      the World Health Organization released a statement on the issue, endorsed by more
      than 80 civil society and health professional organizations worldwide.The
      statement acknowledges a growing body of research that shows widespread patterns
      of women's mistreatment during labor and delivery-physical and verbal abuse,
      neglect and abandonment, humiliation and punishment, coerced and forced care-in a
      range of health facilities from basic rural health centers to tertiary care
      hospitals. Moreover, the statement characterizes this mistreatment as a human
      rights violation. It affirms: "Every woman has the right to the highest
      attainable standard of health, which includes the right to dignified, respectful
      health care throughout pregnancy and childbirth."The WHO statement and the strong
      endorsement of it mark a critical turn in global maternal rights advocacy. It is
      a turn from the public health world of systems and resources in preventing
      mortality to the intimate clinical setting of patient and provider in ensuring
      respectful care. 

PMID- 26204583
TI  - Limiting Rights and Freedoms in the Context of Ebola and Other Public Health
      Emergencies: How the Principle of Reciprocity Can Enrich the Application of the
      Siracusa Principles.
AB  - One of the key components of CESCR General Comment No. 14: The Right to the
      Highest Attainable Standard of Health (GC 14) is the recognition that human
      rights are necessarily interdependent and that the social determinants of health
      are important to the promotion of health itself; as stated in paragraph 3
      "...other [human] rights and freedoms [e.g., food, housing] address integral
      components of the right to health." GC 14, paragraph 16 maintains that a right to
      health also includes the right to control the spread of infectious diseases via a
      variety of control measures, some of which are restrictive. The use of
      restrictive measures during infectious disease outbreaks, including measures like
      quarantine, isolation, and travel prohibitions, restrict or limit basic human
      rights prescribed by the Universal Declaration of Human Rights, such as freedom
      of movement (Article 13) and the right to peaceful assembly (Article 20), for the
      sake of protecting and promoting the health of individuals and communities. 

PMID- 26204584
TI  - How Bioethics is Complementing Human Rights in Realizing Health Access for
      Clinical Trial Participants: The Case of Formative PrEP Access in South Africa.
AB  - Following the demise of apartheid, human rights in South Africa are now
      constitutionally enshrined.The right to health in South Africa's Constitution has
      been credited with transforming the lives of millions of people by triggering
      programmatic reforms in HIV treatment and the prevention of mother to child
      transmission (MTCT) of HIV.However, a constitutionally enshrined right to health
      offers no guarantee that clinical trial participants will enjoy post-trial access
      to beneficial interventions. Using access to HIV pre-exposure prophylaxis (PrEP)
      in South Africa as an example, this paper argues that adherence to bioethics
      norms could realize the right to health for trial participants following the end
      of a clinical trial. 

PMID- 26204585
TI  - The Foundations of a Human Right to Health: Human Rights and Bioethics in
      Dialogue.
AB  - Human rights, including the right to health, are grounded in protecting and
      promoting human dignity. Although commitment to human dignity is a widely shared
      value, the precise meaning and requirements behind the term are elusive. It is
      also unclear as to how a commitment to human dignity translates into specific
      human rights, such as the right to the highest attainable standard of health, and
      delineates their scope and obligations. The resulting lack of clarity about the
      foundations of and justification for the right to health has been problematic in
      a number of ways. This article identifies the strengths of and some of the issues
      with the grounding of the right to health in human dignity. It then examines
      ethical and philosophical expositions of human dignity and several alternative
      foundations proposed for the right to health, including capability theory and the
      work of Norman Daniels, to assess whether any offer a richer and more adequate
      conceptual grounding for the right to health. 

PMID- 26204586
TI  - Human Rights Impact Assessment: A Method for Healthy Policymaking.
AB  - Two decades ago, Lawrence Gostin and Jonathan Mann developed a methodology for
      human rights impact assessment (HRIA) of proposed public health policies. This
      article looks back over the last 20 years to examine the development of HRIA in
      the health field and consider the progress that has been made since Gostin and
      Mann published their pioneering article. Health-related HRIA has advanced
      substantially in three ways. First, the content of the right to health has been
      delineated in greater detail through domestic and international laws and
      policies. Second, the UN human rights mechanisms have recommended that
      governments undertake HRIAs and have issued guidelines and methodologies for
      doing so. Third, nongovernmental organizations and international organizations
      have developed HRIA tools and carried out case studies to demonstrate their
      feasibility. In this light, the article concludes by recognizing the substantial
      progress that has been made in HRIA over the last 20 years and by considering
      some challenges that remain for health-related HRIA. 

PMID- 26204587
TI  - Evolving Human Rights and the Science of Antiretroviral Medicine.
AB  - Recent years have seen significant advances in the science of using
      antiretroviral medicines (ARVs) to fight HIV. Where not long ago ARVs were used
      late in disease to prevent sick people from dying, today people living with HIV
      can use ARVs to achieve viral suppression early in the course of disease. This
      article reviews the mounting new scientific evidence of major clinical and
      prevention ARV benefits. This has changed the logic of the AIDS response,
      eliminating competition between "treatment" and "prevention" and encouraging
      early initiation of treatment for individual and public health benefit. These
      breakthroughs have implications for the health-related human rights duties of
      States. With medical advance, the "highest attainable standard" of health has
      taken a leap, and with it the rights obligations of States. We argue that access
      to early treatment for all is now a core State obligation and restricting access
      to, or failing to provide accurate information about, it violates both individual
      and collective rights. In a context of real political and technical challenges,
      however, in this article we review the policy implications of evolving human
      rights obligations given the new science. National and international legal
      standards require action on budget, health and intellectual property policy,
      which we outline. 

PMID- 26204588
TI  - Evaluating Human Rights Advocacy on Criminal Justice and Sex Work.
AB  - Between October 2011 and September 2013, we conducted research on the use, by
      police and/or prosecutors, of condom possession as evidence of intent to engage
      in prostitution-related offenses. We studied the practice in five large,
      geographically diverse cities in the U.S. To facilitate our advocacy on this
      issue, conducted concurrent to and following our research, we developed an
      advocacy framework consisting of six dimensions: (1) raising awareness, (2)
      building and engaging coalitions, (3) framing debate, (4) securing rhetorical
      commitments, (5) reforming law and policy, and (6) changing practice. Using a
      case study approach, we describe how this framework also provided a basis for the
      evaluation of our work, and discuss additional considerations and values related
      to the measurement and evaluation of human rights advocacy.

PMID- 26204590
TI  - Antiretroviral rounds.  Suppressed but with side effects--now what?

PMID- 26204589
TI  - Raman Reporter-Coupled Ag(core)@Au(shell) Nanostars for in Vivo Improved Surface
      Enhanced Raman Scattering Imaging and Near-infrared-Triggered Photothermal
      Therapy in Breast Cancers.
AB  - Noble-metal nanomaterials were widely investigated as theranostic systems for
      surface enhanced Raman scattering (SERS) imaging, and also for photothermal
      therapy (PTT) of cancers. However, it was still a major challenge to explore
      multifunctional nanoprobes with high performance, high stability, and low
      toxicity. In this work, Raman reporter (DTTC)-coupled Agcore@Aushell nanostars
      (Ag@Au-DTTC) were synthesized and investigated for in vivo improved SERS imaging
      and near-infrared (NIR)-triggered PTT of breast cancers. By the two-step coupling
      of DTTC, the SERS signal was improved obviously, and the cytotoxicity of
      nanoparticles was also decreased by coating Au nanostars onto Ag nanoparticles.
      The as-prepared Ag@Au-DTTC nanostars showed high photostability and excellent
      photothermal performance, in which the photothermal conversion efficiency was up
      to 79.01% under the irradiation of an 808 nm laser. The in vitro and in vivo SERS
      measurements of Ag@Au-DTTC nanostars showed that the many sharp and narrow Raman
      peaks located at 508, 782, 844, 1135, 1242, 1331, 1464, 1510, and 1580 cm(-1)
      could be obviously observed in MCF-7 cells and in MCF-7 tumor-bearing nude mice,
      compared with that in pure DTTC. In 14-day treatments, the tumor volume of MCF-7
      tumor-bearing nude mice injected with Ag@Au-DTTC nanostars and irradiated by an
      808 nm laser almost disappeared. This study demonstrated that the as-prepared
      Ag@Au-DTTC nanostars could be excellent multifunctional agents for improved SERS
      imaging and NIR-triggered PTT of breast cancers with low risk. 

PMID- 26204591
TI  - Updated recommendations on INSTI-based regimens for ART-naive patients.

PMID- 26204592
TI  - Comparative trial of Maraviroc vs. Tenofovir/FTC halted.

PMID- 26204593
TI  - Tenofovir/FTC approved for PrEP...but issues remain regarding implementation.

PMID- 26204594
TI  - New IAS-USA guidelines confirm commitment to universal HIV treatment.

PMID- 26204595
TI  - A debate on liver fibrosis progression in HIV/HCV-coinfected patients.

PMID- 26204596
TI  - Highlights from the 12th International Workshop on Adverse Drug Reactions and Co
      morbidities in HIV.

PMID- 26204597
TI  - Report from the 2012 International Workshop on HIV & Hepatitis Virus Drug
      Resistance and Curative Strategies.

PMID- 26204598
TI  - In memoriam professor Maria Dabska (20.07.1921- 20.07.2014).

PMID- 26204599
TI  - Pigmented Paget's disease of the nipple.
AB  - Pigmented Paget's disease of the nipple (PPD) is an uncommon variant of Paget's
      disease. An accumulation of melanin within the lesion imparts a brow color to the
      affected area, so the lesion might clinically as well as histologically mimic
      melanoma. We present a case of PPD in a 60-year-old woman.

PMID- 26204600
TI  - What is your diagnosis?

PMID- 26204601
TI  - Add soy to your diet, but don't subtract other healthy foods.  Soy foods can help
      you build a healthy diet, but their ability to prevent heart disease and cancer
      remain unproven.

PMID- 26204602
TI  - My doctor recommended I try cognitive behavioral therapy to help treat my
      depression.  What is it, and how can it help me?

PMID- 26204603
TI  - I've been told I should have my varicose veins removed.  What is the danger if I
      don't have them treated?  What is the surgery and subsequent recovery like?

PMID- 26204604
TI  - I am about to have hip replacement surgery.  Afterwards, will I be able to return
      to my pre-arthritis levels of physical activity?

PMID- 26204605
TI  - I need a corneal transplant.  Is it a safe procedure, and what does it entail?

PMID- 26204606
TI  - Mixed-effects models for conditional quantiles with longitudinal data.
AB  - We propose a regression method for the estimation of conditional quantiles of a
      continuous response variable given a set of covariates when the data are
      dependent. Along with fixed regression coefficients, we introduce random
      coefficients which we assume to follow a form of multivariate Laplace
      distribution. In a simulation study, the proposed quantile mixed-effects
      regression is shown to model the dependence among longitudinal data correctly and
      estimate the fixed effects efficiently. It performs similarly to the linear mixed
      model at the central location when the regression errors are symmetrically
      distributed, but provides more efficient estimates when the errors are over
      dispersed. At the same time, it allows the estimation at different locations of
      conditional distribution, which conveys a comprehensive understanding of data. We
      illustrate an application to clinical data where the outcome variable of interest
      is bounded within a closed interval.

PMID- 26204607
TI  - When sleeplessness starts in the legs.  Uncomfortable nighttime leg sensations
      can spoil sleep, but you can take steps to relieve it.

PMID- 26204608
TI  - Making sex pain-free. Discomfort with intercourse happens to men, too. But most
      obstacles can be overcome.

PMID- 26204609
TI  - Better health with smartphone apps.  Downloadable software can educate and
      motivate, helping you to move in a healthier direction.

PMID- 26204610
TI  - What triggers back pain?

PMID- 26204611
TI  - Moderate- and high-intensity workout both burn belly fat.

PMID- 26204612
TI  - Distracting music may trip up older memories.

PMID- 26204613
TI  - Recognizing Real Progress.

PMID- 26204614
TI  - Reducing Heat Stress with HVLS Fans.

PMID- 26204615
TI  - Maintaining Body Temperature in Extreme Conditions with FR Garments.

PMID- 26204616
TI  - Addressing Noise in the Workplace.

PMID- 26204617
TI  - Preventing Occupational and Non-Occupational Head Injuries.

PMID- 26204618
TI  - Hazmat Protection from Head to Toe.

PMID- 26204619
TI  - Disposable Secondary FR Garments: What Really Matters When Selecting a Garment.

PMID- 26204620
TI  - The Evolution of FR Denim.

PMID- 26204621
TI  - Durable Flame Resistance: Comfort and Quality.

PMID- 26204622
TI  - Implementing a Fire Protection Inspection, Testing, & Maintenance Program for
      Water-Based Fire Protection Equipment.

PMID- 26204623
TI  - Technology to the Rescue.

PMID- 26204624
TI  - DOT's Lithium Battery Final Rule Takes Effect.

PMID- 26204625
TI  - Machinery Safety Survey Results: Safety Interlocks and Used Equipment.

PMID- 26204626
TI  - Lagging to Leading to Transformational Indicators: Measuring the Contribution of
      Value.

PMID- 26204627
TI  - Attentionally Avoiding Traps--and Trips.

PMID- 26204628
TI  - CELL-FREE FETAL NUCLEIC ACIDS (cffNA)--NEW NON-INVASIVE PRENATAL DIAGNOSIS.

PMID- 26204629
TI  - IMPLICATIONS OF GHRELIN AXIS IN BREAST CANCER--REVIEW.
AB  - Breast cancer is, by far, the most frequent cancer among women and many factors
      influence the physiological and pathological growth and development of the
      mammary gland. There is developing evidence that the hormone ghrelin, known for
      the growth hormone releasing effect and food intake modulator, could also play a
      role in the pathogenesis of breast cancer and may represent a new diagnostic
      marker and a potential therapeutic target. We performed a PubMed Database search
      of relevant studies and ten papers were included in our systematic review.
      Ghrelin axis seems to be definitely involved in the pathogenesis of breast
      cancer, although a precise role has not been yet established. In order to verify
      the precise role of ghrelin axis in breast cancer further studies with larger
      populations are necessary that should include the analysis of metabolic, genetic
      and environmental factors which are expected to influence the results.

PMID- 26204630
TI  - VITAMIN D DEFICIENCY AND THE CLINICAL CONSEQUENCES.
AB  - Vitamin D is important for good health, growth and strong bones. Vitamin D is
      mostly made in the skin by exposure to sunlight. Most foods contain very little
      vitamin D naturally, though some are fortified with added vitamin D.
      Hypovitaminosis D is associated with cardiovascular disease, the metabolic
      syndrome, type 2 diabetes mellitus, cancer as well as with increased mortality.
      Further, Vitamin D deficiency is related to depression and impaired cognitive
      function. Increasing age and elevated body fat mass contribute to an increased
      risk of Vitamin D deficiency. A mild lack of vitamin D may not cause symptoms but
      can cause tiredness and general aches and pains. A more severe lack can cause s
      rious problems such as rickets (in children) and osteomalacia in adults). During
      menopause, the decline of estrogens results in increased bone turnover, a
      decrease in bone mineral density and elevated fracture risk. Treatment is with
      vitamin D supplements. Some people are more at risk of vitamin D deficiency, and
      so are recommended to take vitamin D supplements routinely. These include all
      pregnant and breastfeeding women, all infants (babies) and young children aged 6
      months to 5 years, people aged 65 and over, and people who are not exposed to
      much sun. There are precise recommendations regarding a sufficient Vitamin D
      intake in order to prevent bone loss in peri- and postmenopausal women. It is
      also recommend routine supplements for certain people with darker skin, and for
      people with certain gut, liver or kidney diseases.

PMID- 26204631
TI  - NEW PERSPECTIVES IN THE DIAGNOSIS AND THE TREATMENT OF CHILDHOOD FEBRILE
      EXANTHEMAS.
AB  - A child with a febrile exanthema is a complex medical problem involving
      diagnostic challenges, epidemiological threats and a great concern for the
      parents and any physician, should be prepared to deal with it. Many of the
      classical ones (measles, rubella, chickenpox) have now a decreased incidence due
      to a high vaccine coverage, which makes even harder for the physician to
      establish an early diagnosis. To the untrained eye most of them are difficult to
      differentiate. Their prompt recognition is necessary in order to manage them
      adequately and to prevent spreading of the disease.

PMID- 26204632
TI  - MYTHS AND CONTROVERSIES IN HYPOGONADISM TREATMENT OF AGING MALES.
AB  - Low T is an independent risk factor for metabolic syndrome (MetS) and type 2
      diabetes mellitus (T2DM) development; patients with these clinical conditions
      should be screened for hypogonadism. Testosterone replacement therapy (TRT)
      ameliorates libido, improves bone mass, improves insulin resistance, reduces fat
      mass and increases lean body mass with no change in body weight. There are no
      evidences that testosterone therapy increases the risk of prostate cancer but it
      is certain that testosterone stimulates growth of metastatic prostate cancer. TRT
      has an antiarrhythmic and a vasodilator effect, independent of the nitric oxide
      effect. Patients with heart failure have low levels of testosterone, and TRT
      improves exercise capacity. Men with low testosterone have risk for premature
      death. Cardiovascular adverse effects of testosterone therapy are under
      discussion. We need large prospective placebo-controlled randomized trials to
      determine definitively the cardiovascular risks of TRT.

PMID- 26204633
TI  - ARE THERE ANY PARTICULARITIES IN CROHN'S DISEASE IN NORTH-EASTERN ROMANIA?
AB  - Crohn's disease is an inflammatory disease of the gastro-intestinal tract with an
      evolution marked by activity and remission periods. Lately, the incidence and
      evolution models of Crohn's disease significantly changed, an increasing number
      of patients presenting more severe forms. The aim of the study is to analyze
      Crohn's disease in its phenotypic classification and to establish correlation
      between the localization, the behavior and the activity of Crohn's disease.
      MATERIAL AND METHODS: A transversal study on 53 patients with Crohn's disease was
      conducted. RESULTS: from the 53 patients, 56.6% were males, 85% from the urban
      areas. Under the phenotype aspect, the colonic localization (49.1%) and the
      inflammatory behavior (52.8%) were predominant. More severe forms of activity
      were discovered to patients with ileal localization (57.1%) or with penetrant
      phenotype (33.3%). CONCLUSIONS: Male patients from urban areas were predominant.
      The most frequent forms are the colonic and ileocolonic forms. From a behavioral
      point of view, we observed an obvious predominance of the inflammatory phenotype.
      The moderate--severe activity was predominant for the ileal localization and the
      mild-- moderate activity for the colonic and ileocolonic localization. A mild-
      moderate activity is present for the stenosing forms and a moderate--severe one
      for the penetrant forms.

PMID- 26204634
TI  - QUALITY OF LIFE IN CROHN'S DISEASE PATIENTS.
AB  - The aim of the study is to assess the impact of Crohn's Disease (CD) on quality
      of life (QoL) patients with and to identify the significant modifications in QoL,
      depending on both the development particularities of CD and the epidemiologic
      parameters. MATERIAL AND METHODS: a prospective study was conducted at the
      Institute of Gastroenterology and Hepathology Iasi, between October 2011 and
      August 2014. The study enrolled 63 patients with CD. The CD diagnosis was based
      on clinical, biological, endoscopic and histological criteria. QoL was assessed
      by means of the IBDQ-32 questionnaire (Inflammatory Bowel Disease Questionnaire).
      RESULTS: The total IBDQ score varied from 70 to 200, registering a slightly
      higher value in female patients. Parameters such as age, sex and smoking/non
      smoking status did not present significant differences in the IBDQ score. The
      values of the IBDQ score were in indirect, mild correlation with the CDAI score;
      over 49% of the subjects with higher CDAI had a lower IBDQ score. CONCLUSIONS:
      Except for the disease activity periods, the results of the studies investigating
      the impact of the various factors on the QoL in patients with CD are
      contradictory. Further research is needed in order to define the subgroups of
      patients likely to suffer from poorer QoL.

PMID- 26204635
TI  - NONALCOHOLIC FATTY LIVER DISEASE AND ITS COMPLICATIONS--ASSESSING THE POPULATION
      AT RISK. A SMALL SERIES REPORT AND LITERATURE REVIEW.
AB  - The aim of the study was to highlight correlations between serum biochemical
      markers and different degrees of liver inflammation or fibrosis revealed by liver
      biopsy in morbidly obese patients. We also wanted to emphasize that the
      occurrence of hepatocellular carcinoma (HCC) is increasingly associated with
      obesity, metabolic syndrome and nonalcoholic fatty liver disease. MATERIAL AND
      METHODS: A clinical retrospective study was carried out on a series of 13
      patients operated for morbid obesity in our surgical unit. Included in this study
      were only the obese patients referred for bariatric surgery without other risk
      factors for liver disease and in whom a liver biopsy was taken during metabolic
      surgery. RESULTS: The pathology report revealed different stages of nonalcoholic
      fatty liver disease in all 13 patients: pathological features of steatohepatitis
      (7 patients), hepatic steatosis (5 patients) and lesions specific for evolving
      cirrhosis (1 patient). Regardless of the pathological changes of the liver,
      except the patient with evolving cirrhosis, none of these patients showed changes
      in classical liver function blood tests. DISCUSSIONS: Hepatic alteration in obese
      patients, ranging from simple steatosis to steatohepatitis or even cirrhosis, is
      not always correlated with the values of classical biological liver function
      tests. Literature data suggest the involvement of adipokines in the development
      and progression of steatosis as the hepatic expression of metabolic and chronic
      inflammation syndrome occurring in obese patients. Furthermore, these proteins
      secreted by adipose tissue seem to be related to the HCC occurrence. However,
      none of these studies show the exact pathway followed by the hepatic cell from
      simple fatty liver to hepatocellular carcinoma. CONCLUSIONS: finding and
      selecting the population at risk for fatty liver disease progression and for HCC
      development among obese patients is mandatory.

PMID- 26204636
TI  - CONGENITAL HEART MALFORMATIONS IN NEWBORN BABIES WITH LOW BIRTH WEIGHT.
AB  - Congenital heart malformations represent a public health problem, holding a
      significant percentage of the total of heart diseases. Beside the elevated
      frequency of the malformations, we also notice their occurrence in newborn babies
      with low birth weight, increasing, thus, the risk of complications and late
      therapeutic approach. The goal of the study was to highlight the general and
      particular aspects of cardiovascular malformations epidemiology in newborn babies
      with low weight at birth, the correlation of the malformations with implied
      genetic and environmental factors, assessing the complications and their
      procedures on the therapeutic management. MATERIAL AND METHODS: Our study was
      performed on a group of 271 patients, hospitalized in the Department of Pediatric
      Cardiology of "Sf. Maria" Emergency Clinical Hospital for Children of Iasi,
      during January 2011-December 2013. The patients were assessed based on anamnesis,
      clinical, biological and imagistic exam. RESULTS: The study lot was divided
      according to the type of the structural defect: 95% of the patients were
      diagnosed with non-cyanogenic congenital heart malformations and 5% with
      cyanogenic congenital heart malformations. Regarding the patient's origin
      background, we notice an elevated frequency of the rural environment (71%). The
      incidence of the malformations was high in premature low birth weight (48%),
      followed by premature very low birth weight (22%). In evolution, congenital heart
      malformations often get more complicated heart failure, arterial hypertension and
      respiratory infections being most often met. Mortality was maximum in the first
      year of life, a third of the cases being associated with chromosomal
      malformations. CONCLUSIONS: Congenital heart malformations in newborn patients
      with low weight at birth represented an elevated percentage of 44.13% of the
      total of the cases hospitalized for cardiovascular diseases from the Department
      of Pediatric Cardiology of Iasi. Many cases were associated with other congenital
      malformations or different complications, being necessary an interdisciplinary
      collaboration to adequately monitor the anatom5ical and functional parameters and
      to ensure a somatic and mental development as normal as possible.

PMID- 26204637
TI  - CHARACTERISTICS OF RESPIRATORY MECHANICS IN CHRONIC OBSTRUCTIVE PULMONARY
      DISEASE.
AB  - In chronic obstructive pulmonary disease (COPD) the changes in respiratory
      thoracoabdominal mechanics result from both hyperinflation and functional and
      structural skeletal muscle alterations. AIM: Evaluation of the particularities of
      respiratory movement in COPD and identification of inter-relations between
      respiratory thoraco-abdominal mechanics and clinical and functional respiratory
      status. MATERIALS AND METHODS: This study comparatively analyzed the respiratory
      thoracoabdominal mechanics recorded by polygraphy, using piezoelectric film
      belts, in 34 COPD patients and 30 healthy subjects, during rest, and during 6
      minute walk test. RESULTS: In COPD patients, phase angle between direction of
      thoracic and abdominal respiratory movements presented significantly higher
      values compared to the control group, for supine (p = 0.023) and sitting position
      (p = 0.001), revealing the presence of paradoxical respiratory movements.
      Furthermore, phase angle dynamics increased significantly during walking test
      compared to sitting position (p = 0.001). Quantitative difference of end
      expiratory pulmonary volume (qDEEL) correlated with pack-years (r = 0.372, p =
      0.03) in supine position, and with body mass (r = 0.338, p = 0.05) and St. George
      activity score (r = 0.353, p = 0.041) during walking test. Rib cage inspiratory
      contribution to tidal volume ratio (%RCi) inversely correlated with pack-years (r
      = -0.417, p = 0.014) and body mass index (r = - 0.344, p = 0.047) in supine
      position, and with St. George activity score (r = 0.345, p = 0.046) in sitting
      position. CONCLUSIONS: In COPD patient thoracoabdominal mechanics is
      characterized by paradoxical respiratory movements, more prominent during
      exercise. The alteration of thoracoabdominal mechanics correlated with St. George
      activity score, pack-years and body mass.

PMID- 26204638
TI  - PSYCHOMETRIC HEPATIC ENCEPHALOPATHY SCORE FOR THE DIAGNOSIS OF MINIMAL HEPATIC
      ENCEPHALOPATHY IN ROMANIAN CIRRHOTIC PATIENTS--PARTIAL RESULTS.
AB  - In Romania, minimal hepatic encephalopathy (MHE) is underdiagnosed and
      undertreated in patients with liver cirrhosis. The psychometric hepatic
      encephalopathy score (PHES) is recommended as the first-line tool for the
      diagnosis of MHE. AIM: To use PHES in a group of Romanian cirrhotic patients and
      highlight the relationships between demographic and biological factors and tests
      results. MATERIALS AND METHODS: Of the 148 patients with liver cirrhosis admitted
      to the Iasi Institute of Gastroenterology and Hepatology between August 2014 and
      February 2015 only 80 who met the eligibility criteria were enrolled and
      completed the study. Blood samples for routine tests and serum ammonia were
      collected from all patients on the day of PHES evaluation. RESULTS: In the study
      group (n = 80) mean age was 57.7 +/- 8.5 years, and the average number of years
      of education was 11.2 +/- 2.7. The main causes of cirrhosis were alcohol
      consumption (31 patients--38.8%), hepatitis C virus infection (29 patients-
      36.3%) and hepatitis B virus infection (17 patients--21.3%). Age, number of years
      of education, severity of liver disease (measured by using Child-Pugh and MELD
      scores) and some biological constants (albumin, bilirubin, International
      Normalized Ratio-INR) were significantly correlated (p < 0.05) with most
      psychometric tests. CONCLUSIONS: PHES is a practical, objective and useful method
      for the diagnosis of MHE. Demographic and biological factors correlated with the
      results of the psychometric test. The PHES requires standardization before
      applying it in Romanian cirrhotic patients.

PMID- 26204639
TI  - CAUSES OF DEATH IN PATIENTS WITH STAGE 0-II BREAST CANCER.
AB  - AIM: To analyze the main causes of death in patients with stage 0-II breast
      cancer who undergo breast conserving surgery or radical mastectomy, and to
      establish the role of imaging surveillance protocols following breast cancer
      treatment. MATERIAL AND METHODS: We conducted a retrospective medical record
      review between January 2005 and December 2012, when breast cancer was the primary
      cause of death for 113 inpatients. All patients were admitted to the Oncology
      Clinic of the Iasi Regional Cancer Institute (IRCI), Romania. Patients were
      stratified by clinical stage 0, I and II, of which 33 (29.2%) patients were
      managed by breast conservation therapy and 80 (70.8%) underwent radical
      mastectomy. From the patient medical records all diagnostic imaging studies
      performed (ultrasound, radiography and computed tomography) were identified and
      analyzed according to a standard protocol for imaging the postoperative breast.
      RESULTS: Bone, liver, lung, lymph nodes and local-regional recurrence were the
      most common sites for metastasis, while the most frequent cause of death were
      metastases to the liver, pleura, lung and brain. The time interval between
      recurrence and death ranged from 0-24 years among patients with one type of
      metastasis, and decreased to 0-3 years since the last recurrence for patients
      with multiple metastases. CONCLUSIONS: The current imaging protocol for
      monitoring the postoperative breast could be optimized to improve the prognosis
      and quality of life in patients with stage 0-II breast cancer.

PMID- 26204640
TI  - BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM --A RAPIDLY EVOLVING ENTITY. CASE
      REPORT.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN), CD4+/CD56+hematodermic
      neoplasm was formally known as blastic NK-cell lymphoma. It is in fact a form of
      acute myeloid leukemia notable for highly aggressive behavior with cutaneous,
      lymph node and bone marrow involvement. This entity is derived from plasmocytoid
      dendritic cells and has a predilection for extranodal sites, especially the skin.
      Elderly male patients are the most affected and the prognostic is poor. The first
      case was reported in 1994 and sice then, single cases and a few small series have
      been published. This article presents the case of a previously healthy 56-years
      old man, who presented himself to a skin eruption consisting in multiple, large
      dermal ulcerated tumors, located on the trunk and scalp. The lesions were
      painless and grew in size rapidly. Physical examination was normal except for the
      skin lesions. Histological examination of a biopsy specimen and
      immunohistochemical studies (positive for next markers: CD4, CD 45, CD56, CD68,
      Ki 67) revealed the rare diagnostic-blastic plasmacytoid dendritic cell neoplasm.

PMID- 26204641
TI  - ATYPICAL PRIMARY HYPERPARATHYROIDISM DUE TO HYPOVITAMINOSIS D.
AB  - Vitamin D deficiency is nowadays very common in the general population and also
      in patients with primary hyperparathyroidism. Hypovitaminosis D may modify the
      clinical features and the severity of primary hyperparathyroidism. We present the
      case of a 75-year-old woman with a 10 year history of nephrolithiasis and severe
      osteoporosis, with multiple fragility fractures. Her bone and kidney status
      required a more thorough metabolic assessment. Despite minimal changes in serum
      calcium and phosphate levels, parathyroid hormone (PTH) level was markedly
      elevated. Ultrasound and specific Sesta-MIBI scintigraphy diagnosed and localized
      a left parathyroid adenoma. Vitamin D assessment showed levels in the range of
      hypovitaminosis. Vitamin D deficiency may mask hypercalcemia despite high serum
      PTH levels, and does not seem to diminish but on the contrary increases the risk
      of kidney lithiasis, as well as the deleterious effects of hyperparathyroidism on
      bone.

PMID- 26204642
TI  - CLINICAL AND PARACLINICAL ASPECTS OF EBSTEIN'S ANOMALY--SEVERE FORM IN NEWBORNS.
AB  - Ebstein's anomaly is a rare heart malformation, with a broad spectrum of anatomic
      abnormalities, leading to different clinical, electrocardiographic,
      echocardiographic changes and a reserved prognosis. We have described a case of
      an infant diagnosed with Ebstein's anomaly--a severe form.

PMID- 26204643
TI  - LIVER METASTASIS OF A GASTROINTESTINAL STROMAL TUMOR OF LARGE BOWEL: CASE REPORT.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal
      malignancies of the digestive tract. We present the case of a 61-year-old male
      patient liver metastasis of a GIST with primary location at the level of sigmoid
      colon. Like in the majority of cases, the symptomatology in this patient has long
      been faint and when it became manifest, it was nonspecific. Imagery wise, the
      computer tomography (CT) scan was the most efficient, showing the origin of the
      tumor from large bowel, its dimensions, as well as the relations with the other
      abdominal viscera and the liver metastasis. Surgery in this patient was en-bloc,
      according to the principles of GIST and for the metastasis he followed treatment
      with Imatinib. The histological aspect is characterized by a proliferation of
      spindle cells positive for CD117 and CD34. Despite complete microscopic
      resection, the exhibit of liver metastasis remains an important relapse factor.

PMID- 26204644
TI  - MONITORING OF RECURRENCE IN PATIENTS RADICALLY OPERATED FOR PANCREATIC CANCER.
AB  - Pancreatic cancer is a diagnosis that carries a poor prognosis. It is the fourth
      leading cause of cancer death in Europe and the United States, despite advances
      in operative technique and postoperative management. Furthermore, there is no
      consensus on the optimal follow-up schedule of patients after surgery for
      pancreatic cancer, all recommendations on surveillance being based on low level
      evidence or no evidence and the leading societies propose different guidelines.
      As a consequence, follow-up strategies may differ between hospitals depending on
      preference of physicians. The vast majority of patients develop recurrence within
      2 years after surgery, suggesting the necessity of a more intensive follow-up the
      first 2 years after surgery. It usually occurs after surgery as migratory
      metastases along major upper abdominal arteries and veins to the liver or
      peritoneum (70%) and less commonly as loco regional disease as masses closely
      applied to the surgical margins in the neck or body of the pancreas (30%).
      Currently, there are no effective means to prevent pancreatic cancer recurrence,
      despite the fact that it is responsible for the majority of postoperative deaths.

PMID- 26204645
TI  - THE IMPORTANCE OF CLINICAL AND INSTRUMENTAL DIAGNOSTIC IN THE MAMMARY GLAND
      CANCER.
AB  - Breast cancer is the most common oncology disease in women and is one of the
      major public health issues. Worldwide, is the second leading cause of cancer
      death in women and cancer research is a priority in all the laboratories of the
      world, in terms of uncovering the appearance causes of the malignant process,
      understanding the mechanisms of development, but most of all, the discovery of
      early diagnostic methods and effective treatment. Ignorance, fear of diagnosis,
      lack of health education and of efficient programmes for prevention and screening
      could cause diagnosis of the disease to be detected in the majority of cases in
      advanced stages, when treatment remains only palliative and very costly, in this
      cases the patient's suffering being immense. In this way, regarding the clinical
      diagnosis in stage I mammary gland cancer, in the 496 stage I MGC patients,
      during the primary clinical investigation the diagnosis of stage I MGC was
      established only in 165 (33.3%) patients, and in 232 (46,8%) patients the
      diagnosis of suspicion MGC was obtained. Also, in terms of instrumental
      diagnosis, such as mammography, ultrasonography in mammary gland cancer stage I,
      it seems that in accordance with literature data the pathological process
      features assessment in the mammary gland is problematic especially in young age.
      Thus, it seems that MGC represents a polymorphic and pathogenic disease and it
      cannot be admitted that all subgroups of patients will obtain identical results
      from one tactic of treatment determined for all the patients with MGC. In this
      way, the concept of MGC both clinical and patho morphological, combines different
      cell clones depending on its microstructure and biology. As a result, the
      evolution of the disease, the prognosis and the effectiveness of the treatment
      may vary in different patients at the same stage, depending on the degree of
      malignancy of the tumor, its histopathological structure, the degree of
      expression of molecular markers identification and also immune resistance.

PMID- 26204646
TI  - BREAST INFECTIONS: DIAGNOSIS WITH ULTRASOUND AND MAMMOGRAPHY.
AB  - AIM: Evaluation of ultrasonographic and mammographic pattern, etiology and risk
      factors of breast infections. MATERIAL AND METHODS: Our study included a group of
      66 female patients aged 16 to 71 years, examined by ultrasound and mammography in
      several medical imaging services in Iasi in the interval 2008-2014; ultrasound
      was performed in all 66 patients and mammography in 22. RESULTS: In our study
      breast infections occurred mostly during breastfeeding and the most frequent
      causative agent was Staphylococcus aureus; ultrasound established the correct
      diagnosis in 63 cases and detected one or more of the following aspects in case
      of breast infections: edema of the fatty tissue, hypoechoic areas in the breast
      tissue, dilated ducts, or fluid collections. Mammography was not necessary in
      puerperal mastitis and was performed only in women over 40 years old; in most
      cases we had encountered a focal asymmetric density which had low specificity for
      the diagnosis of mastitis or breast abscess. CONCLUSIONS: Our study proved that
      ultrasound is a valuable method for the diagnosis of mastitis, especially when an
      abscess is suspected and established a correct diagnosis in most cases; the
      abscesses appear as inhomogeneous fluid collections, with poorly defined margins,
      posterior acoustic enhancement, no Doppler signal inside, sometimes associated
      with enlarged axillary lymph nodes. Mammography was not helpful for the
      diagnosis.

PMID- 26204647
TI  - PALLIATIVE TREATMENT OF MALIGNANT ESOPHAGOPULMONARY FISTULAS WITH COVERED SELF
      EXPANDABLE METALLIC STENTS (SEMSS). A SINGLE CENTER EXPERIENCE.
AB  - AIM: The aim of our study was to determine the efficiency of SEMSs in patients
      with esophagopulmonary fistulas, regarding fistula closure, enhancement of
      dysphagia scores and survival rates. MATERIALS AND METHODS: Between January 2004
      and June 2014, from a total of 133 patients who underwent stent placement
      procedures, 26 were diagnosed with esophagopulmonary fistulas. In 19 cases the
      fistulas were caused by esophageal carcinomas and in 7 cases by bronchogenic
      ones. 16 patients developed aspiration pneumonia, 3 lung abscess and 7
      subclinical fistulas. RESULTS: Complete fistula sealing occurred in 26 patients
      (100%). There were no immediate procedural complications except chest pain in 5
      cases. After sealing of the fistulas and antibiotic treatment, pneumonia has
      regressed. After stent insertion, the dysphagic syndrome improved significantly
      (mean dysphagia scores decrease from 3.28 to 1.3 after stent insertion). The main
      goal of palliative therapy in patients with unresectable cancer and esophago
      pulmonary fistulas is to close the fistulas, thus preventing the aspiration of
      saliva and food into the bronchus. Other goals include amelioration of dysphagia
      symptoms, maintenance of oral intake and improvement of quality of life.
      Ultimately covered expandable metal stents may increase survival rate as compared
      with other therapies. CONCLUSIONS: The endoscopic placement of covered SEMSs is
      the treatment of choice for malignant esophago-pulmonary fistulas.

PMID- 26204648
TI  - MANAGEMENT OF TRAUMATIC LIVER LESIONS.
AB  - AIM: To determine the correct therapeutic approach to the different grades of
      liver trauma. MATERIAL AND METHODS: The study is based on a retrospective
      analysis of treatment outcomes in 56 patients with abdominal trauma admitted over
      a 9-year period to in the IIIrd Surgical Clinic of the Iasi "Sf. Spiridon"
      Hospital. It is focused on operative or non-operative management of liver trauma,
      surgical technique used, morbidity and postoperative mortality. Data were
      collected from electronic medical records and observation sheets and processed
      and interpreted using Microsoft Excel statistical functions. RESULTS: In the
      interval May 26, 2005-April 19, 2013 56 cases of abdominal trauma were recorded,
      31 (55.35%) residing in urban areas, and 25 (44.64%) in rural areas. The mean age
      was 39 years, range 18-83 years old. The male/female ratio was 2.5/1 and the
      group consisted of 40 (71.42%) male patients and 16 (28.57%) female patients. The
      causes of abdominal trauma were: car accident in 29 (51%) cases, fall from
      different heights in 6 (10%) patients, workplace-related accidents in 8 patients
      (14%) and direct hit injury in 12 patients (12%). In our cohort, 51 (91%)
      patients with abdominal trauma have been emergency admitted, 3 patients (5%) were
      transferred from different medical units, and 2 patients (4%) were referred by a
      specialist doctor. Two or more simultaneous lesions were diagnosed in 53 (96%)
      cases. Of the 45 patients with traumatic liver injuries diagnosed on admission,
      32 (71%) required surgical intervention. In the remaining 13 (29%) patients, the
      therapeutic management was conservative. CONCLUSIONS: Hepatic traumas are often
      severe, and frequently associated with multiple injuries. The non-operative
      management is indicated in liver lesions grade I, II and III according to the
      American Association for the Surgery of Trauma (AAST), if abdominal cavity organs
      are not injured. Higher grade liver lesions (over IV) in which the hemorrhagic
      risk persists or reappears require surgical intervention as soon as possible, and
      according to the type of lesion, the right procedure should be chosen.

PMID- 26204649
TI  - A TODAY VICTIM OF SECOND WORLD WAR.
AB  - Emergency medicine as a medical specialty has to deal with all kind of emergency
      situations, from medical to post traumatic acute eyents and from new born to the
      elderly persons, but also with particular situations like explosions. In Romania
      nowadays these are accidental explosions and rare like frequency, but may be
      dramatic due to numbers of victims and multisystem injury that may occur. We
      present a case of a single victim of accidental detonated bomb, a projectile from
      the Second World War, which unfortunately still may be found in some areas. The
      management of the case from first call to 112 until the victim is discharge
      involves high professional team work. We use these opportunity to make a brief
      review of the mechanism through the lesions may appear and also to renew the fact
      that the most impressive lesion may not be the most severe, and we have to
      examine carefully in order to find the real life threatening injury of the
      patient.

PMID- 26204650
TI  - TRAUMATIC SCAPHOLUNATE DISSOCIATION--CASE REPORT.
AB  - Perilunate injuries occur after an impact trauma to the wrist. The recognition of
      these lesions and immediate treatment are the two essential conditions to ensure
      the best possible outcome. The first therapeutic step is the restoration of
      anatomical joint relationships of the carpus followed by percutaneous pinning or
      internal fixation required for maintaining the congruence this segment. Despite
      correct diagnosis and approach in these cases the prognosis is often encumbered
      by decreased range of motion, loss of grip strength and finally the onset of
      osteoarthritis. Scapholunate dissociation is the most frequent pattern of carpal
      instability. We report the case of a 53-year-old woman diagnosed with
      scapholunate dissociation resulting from an injury caused by fall from the same
      level on the outstretched right hand (dominant hand). Surgery was performed 48
      hours post-injury and consisted in external reduction followed after the
      restoration of the anatomical joint relationships in the right wrist by
      percutaneous pinning. Postoperatively the wrist was immobilized in brachipalmar
      cast for 8 weeks and arthrosynthesis pins were removed. The patient was
      reassessed at 6 months postoperatively by clinical and radiological evaluations
      and the functional outcome was good.

PMID- 26204651
TI  - THE EFFECT OF COBALT CHLORIDE PRECONDITIONING ON PACLITAXEL-INDUCED PERIPHERAL
      NEUROPATHY.
AB  - INTRODUCTION: Recent studies indicate that Cobalt Chloride (CoC12) modulates
      mitochondrial activity. There is emerging data suggesting that Paclitaxel-induced
      peripheral neuropathy (PIPN) is a consequence of the drug's mitochondrial
      toxicity. AIM: to assess the effect of CoC12 preconditioning on PIPN in an animal
      model. MATERIAL AND METHOD: PIPN was induced by 7 daily consecutive i.p.
      Paclitaxel (PXT) administrations. Male BALB/c mice were divided into three groups
      as follows: group A--CoC12 (12.5 mg/kg b.w.) for three weeks (preconditioning)
      followed by I week of PXT, group B--saline for three weeks, followed by 1 week of
      PXT and group C--saline for four weeks. Thermal and mechanical allodynia were
      assessed by means of paw withdrawal latency (PWL). RESULTS: In group A, CoC12
      preconditioning lead to a decrease in both thermal and mechanical PWLs. 7 days
      after the last dose of PXT, however, values returned to normal in group A and
      allodynia for both thermal and mechanical stimuli was noted in group B (p <
      0.05). CONCLUSIONS: CoC12 preconditioning seems to protect against PIPN. Although
      CoC12 administration decreased thermal and mechanical PWLs, subsequent P
      administration did not lead to the persistent mechanical and thermal allodynia
      that was noted in the P-alone group. Further studies are required for determining
      the exact relationship between CoC12 and PIPN.

PMID- 26204652
TI  - THE PROGNOSTIC SIGNIFICANCE OF P53, BCL2 AND MIB1 EXPRESSIONS RELATED WITH OTHER
      CLINICOPATHOLOGICAL VARIABLES IN SEROUS OVARIAN CARCINOMAS. A CLINICOPATHOLOGICAL
      STUDY IN PERITONEAL FLUIDS.
AB  - OBJECTIVE: The first cytological study examining the expression of P53, BCL2 and
      MIB 1 expressions in correlation with other clinicopathological parameters in
      ascitic fluids of patients with serous ovarian carcinomas. MATERIALS AND METHODS:
      Fifty women 35-75 years old were diagnosed cytologically and confirmed
      histologically after operation in the University Hospital of Crete. All
      carcinomas were serous type and eight(8) of grade I, eighteen (18) of grade II
      and twenty two (22) of grade III. All carcinomas were staged according to the
      Figo criteria. Fifteen (15) were of Figo stage III and thirty five (35) were of
      Figo stage IV. For p53 and bcl-2, staining was evaluated on a semiquantitative
      scale depending on the number of cells showing positivity. For MIB1, the
      percentage of positive nuclei was calculated. Main outcome measure(s): The
      expression of P53, BCL2 and MIB 1 (Ki 67) correlated with tumor grade and Figo
      stages were estimated by chi-square (chi2). RESULTS: The expression of P53 and
      MIB1 were found to be statistically significant (p < 0.005) correlated with Figo
      stage and tumor grade. A statistical significant correlation was also found
      between BCL2 expression and tumor Grade ( p < 0.005) but not between BCL2
      expression and Figo Stage. The study found a high expression of P53 (64%) and
      MIB1 (72%) and an expression of BCL2 (48%) in ascitic fluid of patients with
      ovarian carcinoma. A statistically significant correlation between P53 and MIB1
      expression correlated with tumor grade and Figo stage (p < 0.005) and a
      statistically significant correlation between BCL2 expression and tumor grade but
      no with the Figo stage was found (p < 0.005). There was a positive correlation
      between P53 and MIB1. No significant association was found between P53 and BCL2
      expression or MIB1 labeling index. CONCLUSION(S): Our data show significant
      differences in the expression of these markers in ovarian tumors and suggest a
      possible role for these tumor-associated genes as supplemental tools in prognosis
      and further definition of the biologic potential of these tumors.

PMID- 26204653
TI  - RELATIONSHIP BETWEEN THE PROANGIOGENIC ROLE OF EG-VEGF, CLINICOPATHOLOGICAL
      CHARACTERISTICS AND SURVIVAL IN TUMORAL OVARY.
AB  - AIM: To prove the presence of EG-VEGF in tumor ovary and to analyze its
      involvement in the ovarian carcinogenesis, as promoter of angiogenesis, in
      relationship with the clinicopathological prognostic factors and survival.
      METHODS: The study group comprises tumor tissue specimens from 50 cases of
      surgically treated ovarian cancer that were immunohistochemically investigated. A
      scoring system based on the percentage of positive cells and the intensity of
      staining was applied for the semiquantitative assessment of EG-VEGF, as negative
      or positive. Statistics involved chi2 test, and Kaplan-Meier and log-rank test.
      RESULTS: EG-VEGF was positive in 35 cases (70%) and negative in 15 cases (30%).
      Our data confirmed the predominance of EG-VEGF positivity in the serous subiype
      as compared to endometrioid and clear cell subtypes, and its absence in mucinous
      subtype. Moreover, we demonstrated that EG-VEGF is overexpressed mainly in high
      grade ovarian carcinomas (type II) than in low-grade ones. Significant
      differences were registered between the EG-VEGF positive or negative expression
      and tumor stage and histological subtypes, respectively. Survival analysis showed
      no differences in patient's survival and EG-VEGF positive and negative cases.
      CONCLUSIONS: The analysis of EG-VEGF expression in ovarian tumors points out the
      relationship between the enhanced potential for tumor angiogenesis and the tumor
      aggressivity.

PMID- 26204654
TI  - THE EFFECTS OF RIBOFLAVIN AND METHYLENE BLUE ON NOCICEPTION AND VISCERAL PAIN.
AB  - BACKGROUND: Methylene Blue (MB) can prevent electron leaking, increase
      mitochondrial oxidative phosphorylation, and reduce ROS overproduction under
      pathological conditions, currently being trace evidence that it can alter pain
      perception in humans by local administration during certain surgical procedures.
      Riboflavin or vitamin B2 (B2) constitutes a part of the vitamin B group, which in
      recent studies shows a growing implication in the treatment of some pathology
      that imply pain management. AIM: To investigate the effect of one dose of
      Riboflavin and Methylene Blue on nociception and visceral pain in mice. METHODS:
      A total of 48 BALB/c male mice were divided into 3 groups: MB Group, B2 Group and
      C Group. MB (5 mg/kg b.w.), B2 (100 mg/kg b.w.) or an equivalent volume of saline
      was administered intraperitoneally. Mice were tested before (baseline) and after
      drugs administration over a 4h period. Nociception was evaluated by means of Hot
      Plate Test (HPT) and TFT (Tail Flick Test). Visceral pain was evaluated 2h after
      administration. RESULTS: Four hours after MB administration we recorded an
      analgesic effect on the hot plate test (p < 0.05 at 30, 60 and 240 min). No
      significant effect on the TFT was noticed. B2 vitamin had an antinociceptive
      effect as compared to control group only for HPT that persisted for 2h but had no
      effect on TFT. Both MB and B2 vitamin have shown an analgesic effect (p < 0.01)
      on visceral pain when compared to the control group but the pain inhibition was
      more important after riboflavin administration. CONCLUSIONS: Even if the exact
      mechanisms are not clarified by our study, we demonstrated that both ATP
      modulators (MB & B2 vitamin) have analgesic effect on visceral pain and
      nociception.

PMID- 26204655
TI  - THE CORRELATION BETWEEN MARKERS OF SYSTEMIC INFLAMMATION AND ANGIOGENIC MARKERS
      IN PRE-ECLAMPSIA.
AB  - Pre-eclampsia is a severe multisystemic syndrome that represents a major cause of
      maternal, foetal and neonatal mortality and morbidity. In the study we conducted
      it stood out the. significant modifications of angiogenic markers in pregnant
      women suffering from pre-eclampsia and the existence of a correlation between C
      reactive protein (CRP) and SBP, DBP and average BP. MATERIAL AND METHOD: The
      group included in the study consisted of 138 pregnant women hospitalized at the
      "Cuza-Voda" Clinical Hospital of Obstetrics and Gynaecology of Iasi, between 2012
      2014, with over 20 weeks gestational age and which gave their free consent to
      take part in the study. RESULTS: It is confirmed the importance of determining
      the markers for diagnosing and monitoring hypertensive pregnant women and at the
      same time it was pointed out that the sFlt-1/PlGF ratio represents a good pre
      eclampsia predictor. CONCLUSIONS: The results of our study confirm the importance
      of determining sFlt-l and PlGF as markers for diagnosing and monitoring pregnant
      women with HBP as well as the sFlt-l/ PlGF ratio which represents a good pre
      eclampsia predictor.

PMID- 26204656
TI  - INTRAOCULAR BIODISTRIBUTION OF INTRAVITREAL INJECTED FLUORESCENT DEXAMETHASONE
      CHITOSAN NANOPARTICLES IN RABBIT EYES.
AB  - AIM: To evaluate intraocular biodistribution of fluorescent nanoparticles
      composed of dexamethasone bound to chitosan after intravitreal administration in
      rabbit eyes. MATERIAL AND METHODS: The chitosan and gelatin based nanoparticles
      were synthetized using a reverse emulsion-double crosslinking technique (ionic
      and covalent) and then dexamethasone was bound. Two units of 1% suspension of
      these nanoparticles in saline solution were injected intravitreally into rabbit
      eyes. The histologic sections obtained at 72 hours were analyzed by confocal
      microscopy. RESULTS: The chitosan-fluorescein conjugate bound to dexamethasone
      was present in all ocular tissues at 72 hours. The nanoparticles were present in
      the retina and lens in a larger amount than in the other ocular tissues.
      CONCLUSIONS: The reverse emulsion-double crosslinking technique was efficient in
      synthesizing a biocompatible polymeric nanosystem. The in vivo study of
      intraocular biodistribution of fluorescein-marked nanoparticles capable of
      binding dexamethasone revealed their affinity for the retina and lens after
      intravitreal administration.

PMID- 26204657
TI  - BIOENERGETIC CHARACTERIZATION OF H9C2 CELLS USING THE EXTRACELLULAR FLUX
      ANALYZER.
AB  - The aim of the present work was to standardize the working methodology for
      assessing the bioenergetic profile of H9c2 cardiomyoblasts cells, with reference
      to the optimization of cell seeding number and the establishment of favorable
      concentrations for the classic modulators of mitochondrial respiratory function,
      in particular the one of a classical uncoupler, FCCP. MATERIAL AND METHODS: The
      extracellular flux analyzer (XF, Seahorse Bioscience) is a novel high-throughput
      instrument able to monitor the metabolism of living cells by simultaneously
      measuring mitochondrial respiration and glycolysis. The in vitro platform will be
      further used to better understand the pathophysiology and the unrecognized side
      effects of drugs currently used in the therapy of major cardiovascular diseases.
      CONCLUSIONS: In the long run, characterization of novel pharmacological agents'
      effects on other cell lines, including tumoral ones, will be also considered.

PMID- 26204658
TI  - ETHICAL MODELS OF PHYSICIAN--PATIENT RELATIONSHIP REVISITED WITH REGARD TO
      PATIENT AUTONOMY, VALUES AND PATIENT EDUCATION.
AB  - The present paper revisits the ethical models of patient--physician relationship
      from the perspective of patient autonomy and values. It seems that the four
      traditional models of physician--patient relationship proposed by Emanuel &
      Emanuel in 1992 closely link patient values and patient autonomy. On the other
      hand, their reinterpretation provided by Agarwal & Murinson twenty years later
      emphasizes the independent expression of values and autonomy in individual
      patients. Additionally, patient education has been assumed to join patient values
      and patient autonomy. Moreover, several authors have noted that, over the past
      few decades, patient autonomy has gradually replaced the paternalistic approach
      based on the premise that the physician knows what is best for the patient.
      Neither the paternalistic model of physician-patient relationship, nor the
      informative model is considered to be satisfactory, as the paternalistic model
      excludes patient values from decision making, while the informative model
      excludes physician values from decision making. However, the deliberative model
      of patient-physician interaction represents an adequate alternative to the two
      unsatisfactory approaches by promoting shared decision making between the
      physician and the patient. It has also been suggested that the deliberative model
      would be ideal for exercising patient autonomy in chronic care and that the
      ethical role of patient education would be to make the deliberative model
      applicable to chronic care. In this regard, studies have indicated that the use
      of decision support interventions might increase the deliberative capacity of
      chronic patients.

PMID- 26204659
TI  - DETECTION OF HUMAN PAPILLOMA VIRUS IN HEAD AND NECK SQUAMOUS CELL CARCINOMAS: A
      LITERATURE REVIEW.
AB  - Human papilloma viruses (HPV) are the most common sexually transmitted viruses.
      There is mounting evidence that incriminates HPV as a risk factor for malignant
      transformation of oropharyngeal epithelium. In 2011 the International Research
      Agency of Cancer and National Cancer Institute (USA) declared HPV-16 as an
      independent risk factor for oropharyngeal squamous cell carcinoma (OPSCC).
      Leaders in the field of HPV research admit that this subtype of head and neck
      cancer is a sexually transmitted entity and its global incidence is on the rise.
      In the 1980s, clinicians observed a new group of patients with head and neck
      squamous cell carcinoma (HNSCC) independent of tobacco smoking or alcohol use.
      The new HNSCC patient is a middle-aged man, non-smoker, non-drinker with higher
      social status and the suspected risk factors for HNSCC being related to sexual
      practices (oral sex, multiple sexual partners, unprotected sex and drug use).
      Routine HPV testing of HNSCC patients is seriously considered as HPV-positive
      oropharyngeal cancers comprise a distinct molecular, clinical and pathologic
      entity that has a markedly better prognosis than HPV-negative oropharyngeal
      cancers. The current treatment protocols for OPSCC include radiation,
      chemotherapy and surgery alone or in combination, involving high toxicity levels.
      Future therapeutic concepts for OPSCC may be personalized in relation to HPV
      status to avoid unnecessary toxicity. The current review summarizes the
      contemporary trends in the diagnosis of HPV-related head and neck cancers,
      presenting the advantages and disadvantages of the main methods.

PMID- 26204660
TI  - ELECTRONIC CIGARETTE--A WAY OF SMOKING CESSATION?
AB  - Specialists have the ethical obligation to promote smoking cessation using
      evidence-based therapeutic strategies. In the context of the growing popularity
      of the electronic cigarettes (ECs), the smokers asking us about it and we must be
      ready to provide expert advice. With the evidence available to date we must be
      cautious in recommending of the smokers to use ECs for smoking cessation because
      these have not proven superiority over drugs used for smoking cessation approved
      by the Food and Drug Administration (FDA), ECs are not FDA approved, short-term
      safety data shows that they cause airway reactivity and health risk of exposure
      to ECs in the long term is unknown. Before the ECs to occupy a place in the
      standard clinical approaches for the treatment of tobacco addiction longer needed
      more data about their safety clinical and regulatory of their use.

PMID- 26204661
TI  - STUDY ON HEALTH PROFESSIONALS' PERCEPTION OF QUALITY OF HEALTHCARE PROVIDED TO
      PATIENTS.
AB  - The quality of the health care system is an essential condition for in improving
      the quality of health services and satisfying both the patients and healthcare
      professionals. RESEARCH OBJECTIVES: To identify the characteristics of medical
      profession, the factors of professional satisfaction or dissatisfaction and
      health care team-related factors that influence the quality of care. MATERIAL AND
      METHODS: Qualitative study using a SurveyMonkey online questionnaire consisting
      of 14 open-ended questions. The respondents were 1013 health professionals in
      university and non-university hospitals with various unit profiles. RESULTS:
      According to healthcare professionals, medical profession is defined by: humanism
      and personal sacrifice (33.37%) and also high professional competence (33.07%).
      Satisfaction factors are: patient health (40.57%), high social status (36.33) and
      saved lives (33.07%). Dissatisfaction may be due to: low salary (39.98%),
      disorganization (38.10%) and lack of procedures (33.96%). Performance may
      decrease as a result of: stressful working conditions, lack of adequate medical
      supplies, lack of recognition at work, routine, and strained relations with
      superiors. CONCLUSIONS: The study shows the need for correlating the medical
      education system and health systems, and for an integrated analysis of both
      systems by determining the required skills and modeling the medical team behavior
      in accordance with the performance variables which take into account satisfaction
      among both patients and health care professionals.

PMID- 26204662
TI  - RETROSPECTIVE EPIDEMIOLOGIC RESEARCH ON PREVALENCE OF INFECTIONS IN SURGICALLY
      TREATED ONCOLOGIC PATIENTS.
AB  - The aim of this work was the retrospective study of the frequency of infections
      in surgically treated oncologic patients. MATERIAL AND METHODS: Our research
      included 753 oncologic patients treated at the Second Surgical Clinic of the
      Regional Institute of Oncology, Iasi, between January 2013 and December 2014,
      with the selection of cases which had infectious complications. RESULTS: The lot
      of patients was structured in 7 age groups and the most frequent oncologic
      patients had ages between 60-79 years. The most frequent malignancies were large
      bowel, breast, rectal, esophageal cancers, malignant hemopathies, gastric and
      liver malignant tumors. In our lot of 753 oncologic patients we depicted 113
      (15.01%) infections. CONCLUSIONS: Our study proved that the anatomic location of
      the cancer, the hospitalization duration and the number of the hospitalizations
      has an important role in appearance of the infectious complications. The
      gastrointestinal malignant tumors were the most frequent malignancies associated
      with postoperative infections. The patients with gastrointestinal cancers from
      urban area, with ages between 50 and 79 years had the highest risk of infectious
      complications. For main causative organism was proved a high sensitivity for
      colistin. Clinical, paraclinical and epidemiological exams did not emphasize any
      decisive factors; we took into account the risks of infection during multiple pre
      , intra- and postoperative procedures; all these have been associated with
      increased receptivity of immunosuppressed oncologic patients.

PMID- 26204663
TI  - QUALITY OF LIFE WITH MASTECTOMY FOR BREAST CANCER, IN TERMS OF PATIENTS'
      RESPONSES OF SF-36 QUESTIONNAIRE.
AB  - The aim of the study was to describe the quality of life in female patients with
      mastectomy performed for breast cancer. MATERIAL AND METHODS: The study was
      carried out in Iasi, between October 2014-January 2015, on a sample of 23
      patients with mastectomy, using the SF-36 Questionnaire (Short Form-36) in a
      single visit, with direct questioning of patients; a secondary instrument was a
      general anamnestic questionnaire referring on age group, area of residence, type
      of surgery, associated diseases, family history, psycho-emotional traumas.
      RESULTS: The overall profile of the studied case was: woman of 40-49 years
      (47.8%), from urban area (82.6%), with a family history of neoplastic pathology
      (43.5%), with psycho-emotional traumas (73.9%) and a self-estimated general
      health as "moderate" (26.1%), with "a lot of energy" only "some of the time"
      (43.5%), "feeling worn out" (43.5%), and "cutting down the amount of time spent
      on work or other activities" (69.6%), with "moderate" (34.8%) or even "intense"
      (21.7%) "bodily pain", "some of the time" feeling "very nervous" (43.5%) and "so
      down in the dumps that nothing could cheer her up" (39.1%). The strongest
      correlation was found between the variable "cut down the amount of time spent on
      work and other activities" as a result of "physical health" (Role-physical items)
      and "limited in kind of work or other activities" (r = 0.898 1). CONCLUSIONS:
      Application of SF-36 Questionnaire in female patients with mastectomy for breast
      cancer highlighted that strenuous and moderate activities were limited than about
      half of the surveyed cases, somatic pain affecting their work and normal
      activities and physical and emotional health influenced the social activity of
      patients for more than half of the lot. It is necessary to extend the study in
      order to bring relevant data on the quality of life of these patients, in the
      social, economic and cultural center of Romania.

PMID- 26204664
TI  - ANTIBIOTIC RESISTANCE SPECTRUM OF NON FERMENTING GRAM NEGATIVE BACILLI ISOLATED
      IN THE ORTHOPEDIC TRAUMATOLOGY CLINIC OF "SF. SPIRIDON" CLINICAL EMERGENCY
      HOSPITAL IASI.
AB  - AIM: The retro-prospective analysis of antibiotic sensitivity of non-fermenting
      gram negative bacilli strains circulating in the Orthopedics-Traumatology Clinic
      from "Sf. Spiridon" Emergency Clinical Hospital in view of determining the trend
      of the resistance phenomenon and indicating the most useful treatment for the
      infections caused by these strains. MATERIAL AND METHODS: The retrospective
      component was conducted from 01.01.2003 to 31.12.2012, and the result of the
      diffusimetric antibiograms was taken from the hospital's informatics system; the
      prospective component of the study involved the collection of pathological
      products from the patients admitted during January-December 2013, who showed
      clinical suspicion of infection, in compliance with the general collection norms
      for the products destined for the bacteriological exam. RESULTS: From the total
      167 strains of Pseudomonas aeruginosa isolated and identified from the patients,
      48 (28.74%) were sensitive to at least one antibiotic from each tested class, 29
      (17.39%) were resistant to a single antibiotic and the rest of 90 (53.89%) showed
      multiple resistance. We noticed a statistically significant difference between
      the number of strains sensitive to at least one antibiotic from each tested class
      and those with multiple resistance (p < 0.05). For the strains of Acinetobacter
      baumanii combined resistance was identified for 121 (87.04%), out of which 55
      (39.56%) were resistant to two classes of antibiotics and the other (47.48%) to
      all three classes. The most frequently met was the association of resistance to
      quinolones and aminoglycosides, namely for a number of 49 strains (35.25%); only
      3.59% of them were simultaneously sensitive to the three classes of antibiotics.
      CONCLUSION: The already high percentages and the rising trends of antibiotic
      resistance of non-fermenting gram-negative bacteria described in this study
      confirm the continuous decrease of the efficiency of antimicrobial agents and
      underline the necessity of a global strategy which aims at all health sectors
      regarding the rational use of antibiotics, on the one hand, and the continuation
      of studies concerning the surveillance of the antimicrobial resistance
      phenomenon, on the other hand.

PMID- 26204665
TI  - A PRELIMINARY EVALUATION OF RESIDENTS' PERCEPTION OF THEIR TRAINING AND KNOWLEDGE
      ON THREE-DIMENSIONAL IMAGING.
AB  - The aim of this preliminary study was to assess the residents' perception on
      their training program and on their knowledge regarding the use and
      interpretation of three-dimensional imaging techniques in their clinical
      practice. MATERIAL AND METHODS: A multi-item questionnaire was distributed among
      104 residents training in four medical specialties at the University of Medicine
      and Pharmacy "Grigore T. Popa" in Iasi. RESULTS: Fifty-five residents agreed to
      fill in the questionnaire, achieving a participating rate of 52.88%. The majority
      of the respondents (74.5%) declared to indicate classic CT scans to their
      patients. A significantly lower fraction of the participating residents (32.7%)
      affirmed to indicate CBCT scans. Electronic literature was the most common
      information source on the use of three-dimensional imaging (52.7%). Most of the
      residents declared that they cannot interpret correctly CT and CBCT scans (78.2%,
      respectively 83.6%). A significant percentage of the respondents considered that
      the level of training provided on the interpretation of CT and CBCT results is
      very low (49.1%, respectively 60.0%). CONCLUSIONS: The residents' perception of
      the quality of their education regarding 3D imaging modalities, along with their
      perception of their knowledge in this area, indicates the necessity to improve
      their didactic and practical training. A further extended survey will be
      conducted to evaluate the educational experience of residents from all medical
      specialties that use 3D imaging techniques in neck and head imaging.

PMID- 26204666
TI  - DENTAL STUDENTS' PSYCHOLOGICAL WELL-BEING DURING EXAMINATION PERIOD AND HOLIDAY.
AB  - INTRODUCTION: Psychological well-being is recognized as an important health
      component, which influences the behavior, ability to cope with stressful events,
      work performance, and generally the ability to achieve one's full potential. AIM:
      To comparatively assess the psychological well-being of dental students during
      the summer semester examination period and summer holiday. MATERIAL AND METHODS:
      A single-arm, prospective study was conducted in second year dental students from
      the Faculty of Dental Medicine, Bucharest. The psychological well-being was
      assessed using the WHO-Five Well-being Index. RESULTS: Students' psychological
      well-being was statistically significantly better during the summer holiday
      (median=19) than during the summer semester examination period (median = 11.5), Z
      = 3.69, p < .001. The perceived satisfaction regarding financial means, faculty
      colleagues, home, family and overall life satisfaction was the same during summer
      semester examination period and summer holiday, but it was significantly
      correlated with the WHO-Five Well-being Index score corresponding to the summer
      holiday, and no association was observed with the WHO-Five Well-being Index score
      corresponding to the summer semester examination period. CONCLUSIONS: Within the
      limits of this study, psychological well-being is likely to be negatively
      influenced, on a fairly large scale, by the semester examination period.
      Therefore, it is recommended to identify the most appropriate methods of
      examination with regards to the psychological load that might be a threat to the
      validity of students' evaluation. Additionally, training students about adequate
      coping strategies, designed as interventions at individual or group level, may be
      required.

PMID- 26204667
TI  - METHODS OF INTEGRATING AESTHETIC REHABILITATION INTO THE TREATMENT PLAN OF
      ELDERLY PATIENTS.
AB  - Dental aesthetics represents a synonym for modern, cutting edge dentistry as it
      is a simultaneous mixture of art and science. The materials and the technology
      nowadays provide the resources for achieving extremely accurate and physiognomic
      restorations regardless of the amplitude of the intervention needed; consequently
      the treatment must respect the oral health and the optimal functioning of the
      dental-maxillary apparatus. One of the treatment phases that precede the final
      result, one step ahead in the treatment, is represented by the temporary
      restoration. The purpose of the paper consists in assessing the importance of
      restoring a patient's facial aesthetics--a key element for treatment success,
      while going through the phases that precede the final result. MATERIAL AND
      METHOD: The study includes 88 patients aged between 60-90 years (median age--75
      years), treated at the Department of Oro-dental Diagnosis and Gerontostomatology,
      between January 2012 and December 2013. The patients requested the restoration of
      the functions affected by odontal coronary lesions, periodontal disease or
      edentation, malocclusion, cranial mandibular malrelations, and unsuccessful or
      deteriorated odontal or prosthetic treatments. RESULTS: Dental aesthetics implies
      a detailed assessment of each individual case because the long term success of
      the beautiful result achieved depends of the optimal state of health and
      functionality of the entire system. The final project in the cases studied was
      transformed into temporary restoration and afterward into permanent restoration.
      CONCLUSIONS: The use of temporary prosthesis within the treatment plan is
      important for the patient as it contributes at maintaining his social life active
      and also at developing the correct techniques for providing the proper hygiene
      for the restored elements.

PMID- 26204668
TI  - RISK FACTORS AND PREDICTORS OF CROSSBITE AT CHILDREN.
AB  - AIM: was to determine the etiological risk factors and predictors of crossbite'
      treatment at children. MATERIAL AND METHODS: 270 cases with crossbites and 255
      controls with other malocclusions were uniformly evaluated. The crossbites cases
      were divided in group I (anterior crossbite), group II (posterior crossbite) and
      group III (anterior and posterior crossbites) and were compared between them per
      Angle Class malocclusions, dysfunctional and dental causes, associations with
      other discrepancies, as well by need and types of treatment. Binary logistic
      regression was used to find risk factors and predictors. RESULTS: The mean age of
      cases was 10.25?2.770 years. There were found significant differences between the
      groups of crossbites cases (p<0.05). There were identified risk factors (non
      attrition of deciduous teeth, Angle Class II malocclusion and permanent teeth
      extraction) and protective factors of the crossbite (the tooth decay of deciduous
      teeth, eruption anomalies and tongue-thrust swallowing). There were found
      predictors for early corrective treatment (sucking habit, non-attrition and buds
      crowding) with a precision of 78.5%; for normal treatment (mouth breathing and
      buds crowding) with a precision of 71.5%; for late treatment (Angle Class III
      malocclusion, dental crowding and TMJ disorders) with a precision of 83.0%; for
      maxillary expansion (eruption anomalies and buds crowding) with a precision of
      77.0%; for oral associated surgery (macrodontia and TMJ disorders) with a
      precision of 75.9% (HL test, p > 0.05). CONCLUSION: The risk factors were dental
      furthermore; the predictors of treatment were adequate with dentition, etiology
      and disorders at age identification, suggesting the contribution of practitioners
      in intercepting this orthodontic emergency.

PMID- 26204669
TI  - SECOND MOLAR UPRIGHTING AFTER PREMATURE LOSS OF MANDIBULAR FIRST PERMANENT MOLAR-
      CASE REPORT.
AB  - INTRODUCTION: Uprighting a tipped molar by using an uprighting spring is a
      fundamental orthodontic treatment technique. Following a weak anchorage done only
      by the anterior teeth the permanent lower second molar will rotate around its
      center of resistance, and besides the distalizing movement will occur its
      extrusion. Following the reaction, the mandibular anterior teeth will have a
      movement of intrusion. All these elements will lead to anterior open bite.
      Correction of vertical problems has become easier with the advent of mini
      implants. CASE PRESENTATION: U.I patient aged 24 years presenting for aesthetic
      and functional disorders. Clinical examination reveals intraoral Class I molar
      malocclusion on the right sight, upper narrowing arch with a slight overbite, and
      the both permanent first molars on the left side lost prematurely. The tooth 37
      is inclined at 600 degrees to the plane of occlusion. To avoid front opening
      occlusion we used an orthodontic miniscrew inserted between the canine and the
      first premolar on the same side to achieve the second molar up righting. Lower
      second molar uprighting was achieved without unwanted movements in anterior
      mandibular region and without molar extrusion. CONCLUSIONS: Using mini implants
      in uprighting a tipped molar will achieve the desired tooth movement and will
      reduce the number of unwanted side effects and eventually to improve patient's
      esthetics.

PMID- 26204670
TI  - HYPOGLYCEMIA INDUCED BY ANTIDIABETIC SULFONYLUREAS.
AB  - Diabetes mellitus is a major health problem due to its increasing prevalence and
      life-threatening complications. Antidiabetic sulfonylureas represent the first
      line drugs in type 2 diabetes even though the most common associated risk is
      pharmacologically-induced hypoglycemia. In the development of this side effect
      are involved several factors including the pharmacokinetic and pharmacodynamic
      profile of the drug, patient age and behavior, hepatic or renal dysfunctions, or
      other drugs associated with a high risk of interactions. If all these are
      controlled, the risk-benefit balance can be equal to other oral antidiabetic
      drugs.

PMID- 26204671
TI  - FIXED DOSE COMBINATIONS WITH SELECTIVE BETA-BLOCKERS: QUANTITATIVE DETERMINATION
      IN BIOLOGICAL FLUIDS.
AB  - Hypertension is one of the most common causes of death, a complex and
      incompletely controlled disease for millions of patients. Metoprolol, bisoprolol,
      nebivolol and atenolol are selective beta-blockers frequently used in the
      management of arterial hypertension, alone or in fixed combination with other
      substances. This study presents the most used analytical methods for simultaneous
      determination in biological fluids of fixed combinations containing selective
      beta-blockers. Articles in Pub-Med, Science Direct and Wiley Journals databases
      published between years 2004-2014 were reviewed. Methods such as liquid
      chromatography--mass spectrometry--mass spectrometry (LC-MS/MS), high performance
      liquid chromatography (HPLC) or high performance liquid chromatography--mass
      spectrometry (HPLC-MS) were used for determination of fixed combination with beta
      blockers in human plasma, rat plasma and human breast milk. LC-MS/MS method was
      used for simultaneous determination of fixed combinations of metoprolol with
      simvastatin, hydrochlorothiazide or ramipril, combinations of nebivolol and
      valsartan, or atenolol and amlodipine. Biological samples were processed by
      protein precipitation techniques or by liquid-liquid extraction. For the
      determination of fixed dose combinations of felodipine and metoprolol in rat
      plasma liquid chromatography--electrospray ionization--mass spectrometry (LC-ESI
      MS/MS) was applied, using phenacetin as internal standard. HPLC-MS method was
      applied for the determination of bisoprolol and hydrochlorothiazide in human
      plasma. For the determination of atenolol and chlorthalidone from human breast
      milk and human plasma the HPLC method was used. The analytical methods were
      validated according to the specialized guidelines, and were applied to biological
      samples, thing that confirms the permanent concern of researchers in this field.

PMID- 26204672
TI  - EFFECTS OF ZINGIBER OFFICINALE ROSCOE FRESH EXTRACT ON AMELANOTIC MELANOMA AND
      NORMAL SKIN FIBROBLASTS.
AB  - Zingiber officinale Roscoe is a very important medicinal plant, with a long
      history of therapeutic uses, especially in oriental traditional medicine. AIM: To
      investigate the cytotoxicity of a fresh ginger extract on some skin tumor cells
      compared to normal cells. MATERIAL AND METHODS: C32 amelanotic melanoma cell line
      and CCD human skin fibroblasts were used. The fresh extract obtained by crushing
      ginger rhizome was examined for phenolic content. The in vitro cytotoxicity was
      examined using phase contrast microscopy and MTT assay for the concentrations of
      2 and 4 mg% total phenols. RESULTS: Both concentrations used for treatment
      induced no changes in normal the morphology and viability of fibroblasts compared
      to control cells. Amelanotic melanoma cells displayed profound changes in cell
      morphology such as cell shrinkage, rounding-up and membrane blebbing and a
      decrease in cell viability in a dose-dependent manner. CONCLUSIONS: Fresh ginger
      extract induced no changes in normal skin fibroblast viability, but caused
      profound cytotoxic effects on amelanotic melanoma. These results could encourage
      further studies regarding the intimate mechanisms of the antitumor action
      displayed by the fresh ginger extract.

PMID- 26204673
TI  - ANTIOXIDANT AND PHYTOBIOLOGICAL STUDIES ON TWO ALLIUM CEPA L. EXTRACTS.
AB  - AIM: To investigate the antioxidant potential of two Allium cepa L. extracts.
      MATERIAL AND METHODS: The antioxidant activity of the two extracts (encoded EC1
      and EC2) was assessed using two methods: DPPH (2,2-diphenyl-1-picrylhydrazyl)
      scavenging capacity and determination of their reducing power; phytobiological,
      studies were performed using grains of Triticum aestivum L., Falmura variety.
      RESULTS AND DISCUSSIONS: EC1 and EC2 extracts had a particular affinity for
      binding DPPH radicals. At equivalent concentrations, the reducing power of
      EClextract was about 2 times higher compared to EC2, increasing with the
      concentration of the analyzed sample. The phytobiological study demonstrated that
      the investigated extracts had no cytotoxic and genotoxic potential.

PMID- 26204674
TI  - ISOLATION, CHARACTERIZATION AND ANTIOXIDANT ACTIVITY OF THE CRUDE POLYSACCHARIDE
      FROM PHYLLOPHORA PSEUDOCERANOIDES.
AB  - The red seaweed Phyllophora pseudoceranoides (Gmelin) New. et Tayl, commonly
      found in the Romanian Black Sea coastal waters, has not been studied regarding
      its chemical composition and biological activities. AIMS: The aim of the present
      study was to isolate, characterize and assess the in vitro antioxidant activity
      of the crude polysaccharide from P. pseudocerano ides. MATERIALS AND METHODS: The
      water soluble polysaccharide was characterized by Fourier transform infrared
      spectroscopy (FT-IR). Total phenolic content was determined by Folin-Ciocalteu
      method. Antioxidant activity was evaluated by ABTS radical cation scavenging and
      reducing power assays. Commercial-grade carrageenan was used as positive control.
      RESULTS AND DISCUSSION: FT-IR analysis of the crude polysaccharide showed
      characteristic bands of carrageenan-type structure. A total phenolic content of
      25.08 +/- 1.00 mg GAE/g was determined in the crude polysaccharide. At 1.5 mg/mL,
      the polysaccharide exhibited important ABTS scavenging activity (49.59 +/- 0.03%)
      and showed a good reducing power (0.4060 +/- 0.002), when compared with the
      positive control (ABTS scavenging activity: 30.30 +/- 0.03% and reducing power:
      0.2494 +/- 0.002, at a concentration of 1.5 mg/mL). CONCLUSIONS: The antioxidant
      activity of the sulfated polysaccharide suggests its possible use as an
      ingredient and antioxidant agent in the food and pharmaceutical industries.

PMID- 26204675
TI  - GRAPHICAL USER INTERFACE WITH APPLICATIONS IN SUSCEPTIBLE-INFECTIOUS-SUSCEPTIBLE
      MODELS.
AB  - Practical significance of understanding the dynamics and evolution of infectious
      diseases increases continuously in contemporary world. The mathematical study of
      the dynamics of infectious diseases has a long history. AIM: By incorporating
      statistical methods and computer-based simulations in dynamic epidemiological
      models, it could be possible for modeling methods and theoretical analyses to be
      more realistic and reliable, allowing a more detailed understanding of the rules
      governing epidemic spreading. MATERIAL AND METHODS: To provide the basis for a
      disease transmission, the population of a region is often divided into various
      compartments, and the model governing their relation is called the compartmental
      model. To present all of the information available, a graphical user interface
      provides icons and visual indicators. The graphical interface shown in this paper
      is performed using the MATLAB software ver. 7.6.0. MATLAB software offers a wide
      range of techniques by which data can be displayed graphically. The process of
      data viewing involves a series of operations. To achieve it, I had to make three
      separate files, one for defining the mathematical model and two for the interface
      itself. RESULTS: Considering a fixed population, it is observed that the number
      of susceptible individuals diminishes along with an increase in the number of
      infectious individuals so that in about ten days the number of individuals
      infected and susceptible, respectively, has the same value. If the epidemic is
      not controlled, it will continue for an indefinite period of time. By changing
      the global parameters specific of the SIS model, a more rapid increase of
      infectious individuals is noted. CONCLUSIONS: Using the graphical user interface
      shown in this paper helps achieving a much easier interaction with the computer,
      simplifying the structure of complex instructions by using icons and menus, and,
      in particular, programs and files are much easier to organize. Some numerical
      simulations have been presented to illustrate theoretical analysis.

PMID- 26204676
TI  - Pathology of balloon-expandable and self-expanding stents following MRI-guided
      transapical aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Balloon-expandable (BE) and self-expanding (SE)
      prostheses are both used for transcatheter aortic valve replacement (TAVR), but
      differences in long-term outcome using these types of device are unknown. The
      study aim was to monitor the histopathology, echocardiographic findings and
      structural integrity of BE and SE stents in a preclinical model for up to six
      months after TAVR. METHODS: Real-time magnetic resonance imaging (rtMRI)-guided
      TAVR was performed in 22 Yucatan pigs using either a BE (n = 10) or a SE (n = 12)
      prosthesis. Follow up echocardiography and MRI studies were performed at one-,
      three-, and six-month intervals. Additionally, high-contrast radiography was used
      to assess for strut fractures. The pigs were sacrificed after six months and
      tissues taken for histopathologic analysis. RESULTS: Stent malapposition was
      found in seven BE prostheses (70%), and in three SE prostheses (25%) (p = 0.046).
      Three of the SE group (25%) had a partial left coronary artery obstruction. The
      incidence and severity of aortic regurgitation were similar between the BE and SE
      groups. Three BE prostheses (30%) and one SE prosthesis (8.3%) had a gap between
      the stent frame and aorta. The mean (+/-SD) number of strut fractures was 6.1 +/-
      3.45 and 1.17 +/- 2.32 in the BE and SE groups, respectively (p = 0.002). In
      addition, two implanted BE prostheses (20%) had a consequential compressed stent
      frame appearance. CONCLUSION: Long-term pathologic examination of necropsy
      specimens from a preclinical model of rtMRI-guided TAVR showed SE stent
      prostheses to be superior to their BE counterparts in terms of correct valve
      apposition and durability. These results may be attributed to the differing
      deployment methods and associated expansion forces employed by the BE and SE
      stents.

PMID- 26204677
TI  - Valvulo-arterial impedance is the best mortality predictor in asymptomatic aortic
      stenosis patients.
AB  - BACKGROUND AND AIM OF THE STUDY: Risk stratification is particularly complex in
      asymptomatic patients with significant aortic stenosis (AS). The study aim was to
      assess which hemodynamic/Doppler-echocardiographic parameter best predicts
      mortality in asymptomatic patients with severe AS and a normal left ventricular
      ejection fraction (LVEF). METHODS: This prospective study included 128
      consecutive asymptomatic patients (75 males, 53 females; mean age 66.35 +/- 10.51
      years) with severe AS (aortic valve area (AVA) +/- 1.0 cm2) and a normal LVEF
      (55%). The patients were followed up for 47 months (median 35.5 months, IQR 7
      months). Clinical data at follow up were obtained from all patients by either
      direct examination or telephone interview. RESULTS: During the follow up, 55
      patients (43.0%) underwent aortic valve replacement (AVR) surgery due to AS
      related symptoms. Of the 12 patients that died (9.4%), eight deaths occurred
      before surgery (four patients refused operation), and one patient died after
      surgery due to postoperative infection. Those patients who died had a
      significantly higher valvulo-arterial impedance (Z(va)) (7.81 versus 4.86 mmHg x
      ml/m2, p < 0.001), a higher N-terminal pro-brain natriuretic peptide (NT-proBNP)
      level (1708.5 versus 376.5 pg/ml, p = 0.003) and a lower AVA (0.65 versus 0.86
      cm2, p = 0.002), but there were no differences in LVEF, P(mean) or age between
      the groups (69.68% versus 72.24%, p = 0.206; 44.95 versus 41.75 mmHg; and 69
      versus 66 years, p = 0.332, respectively). When parameters that were predictors
      of mortality according to univariate analysis were further analyzed with Cox
      multivariate analysis, Z(va) was found to be the best independent predictor (B =
      0.460, HR = 1.584, 95% CI = 1.064-2.359, p = 0.024). A Z(va) value of 6.1 mmHg x
      ml/m2 was identified as the best (cut-off) predictive value for the occurrence of
      death, with a sensitivity 61.1% and a specificity 86.0%. CONCLUSION: Z(va) is the
      best mortality predictor in asymptomatic patients with severe AS and a normal
      LVEF. Future studies are required to focus further on predictors of outcome, the
      aim being to achieve an optimal selection of asymptomatic patients considered to
      be at risk and who would benefit from early AVR.

PMID- 26204678
TI  - Clinical value of ankle-brachial index in asymptomatic aortic stenosis patients.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the prevalence and
      clinical value of the pathological ankle-brachial index (ABI) in asymptomatic
      aortic stenosis (AS) patients. METHODS: This prospective study included 203
      asymptomatic AS patients, with a mean follow up of 18 +/- 10.6 months. Six-minute
      walk tests (6MWT) and ABI measurements were performed when patients were included
      in the study. Study events were defined as death, hospital admission due to
      related symptoms, or a need for surgery. RESULTS: A total of 198 patients (95
      females, 103 males; mean age 74.6 +/- 9.5 years) completed the study. An abnormal
      ABI was found in 35.8%. Mean (+/- SD) values were: peak velocity Vmax 4.1 +/- 0.8
      m/s; maximum/mean gradient 70.5 +/- 25.1/43.3 +/- 16.3 mmHg; aortic valve area
      0.8 +/- 0.7 cm2; indexed aortic valve area 0.4 +/- 0.1 cm2/m2. A pathological ABI
      was associated with diabetes (p = 0.01), previous peripheral vascular disease (p
      = 0.04) and previous stroke (p = 0.04). In multivariate analyses, diabetes was an
      independent factor related to pathological ABI (relative risk 1.71, 95% CI 1.22
      2.19). Patients with a pathological ABI walked less in the 6MWT (263.9 m versus
      328.3; p = 0.002), but did not present a worse prognosis at follow up (p = NS).
      CONCLUSION: Among asymptomatic AS patients, 35.8% had an abnormal ABI and this
      was related to previous diabetes. These patients walked less in the 6MWT but did
      not have a worse prognosis at follow up.

PMID- 26204679
TI  - Iatrogenic mitral valve chordal rupture during placement of an inflatable and
      repositionable percutaneous aortic valve prosthesis.
AB  - A case is reported of iatrogenic mitral valve chordal rupture occurring during
      transcatheter aortic valve implantation (TAVI) with an inflatable and
      repositionable valve (Direct Flow; Direct Flow Medical, Santa Rosa, CA, USA). The
      specific implantation technique requires initial valve advancement into the left
      ventricular cavity, valve inflation within the ventricular cavity, and a final
      finely tuned valve upward pulling through the left ventricular outflow tract
      until contact with the aortic annulus is achieved. During this phase of the
      procedure, entangling with the mitral subvalvular apparatus should be excluded,
      to avoid inadvertent tissue tearing and consequent mitral valve malfunction. The
      present patient underwent TAVI but then developed symptomatic severe mitral valve
      regurgitation resulting from chordal rupture. The condition was successfully
      treated percutaneously by implanting a Mitra-Clip.

PMID- 26204680
TI  - Transaortic aortomitral junction reconstruction and mitral valve leaflet repair
      for recurrent endocarditis.
AB  - Transaortic interventions on the mitral valve are rarely performed, but offer
      advantages over traditional approaches in certain circumstances, including either
      extensive involvement of the aortomitral junction with endocarditis or the
      patient requiring reoperation for aortic and mitral disease. Herein is presented
      a case of recurrent endocarditis involving aortomitral continuity, reconstructed
      using a transaortic mitral valve repair and reconstruction of the aortic and
      mitral annuli with a pericardial patch, followed by aortic root replacement.

PMID- 26204681
TI  - Impella-assisted balloon aortic valvuloplasty as a bridge to transcatheter aortic
      valve replacement: non-contrast approach.
AB  - Patients with severe aortic stenosis (AS) and left ventricular dysfunction are
      susceptible to hemodynamic decompensation due to limited myocardial reserve.
      Recent reports have suggested a role for hemodynamic assist devices such as the
      Impella or TandemHeart for improved in-hospital outcomes. However, the use of
      iodinated contrast during this vulnerable period poses a high risk for the
      development of contrast-induced nephropathy. A strategic approach is described
      for the treatment of high-risk patients with severe AS and cardiogenic shock,
      utilizing Impella-assisted balloon aortic valvuloplasty (BAV), without the
      administration of iodinated contrast as a bridge to transcatheter aortic valve
      replacement.

PMID- 26204682
TI  - The impact of a minimally invasive approach on reoperative aortic valve
      replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: The advantages of minimally invasive aortic
      valve replacement (AVR) are well documented, but whether the benefits extend to
      subsequent reoperative aortic valve surgery and beyond is unknown. The study aim
      was to compare in-hospital outcomes and long-term survival following reoperative
      AVR between patients who had previous undergone either minimally invasive AVR
      (mini-AVR) or full sternotomy AVR (sAVR). METHODS: All reoperative, isolated AVRs
      performed between July 1997 and September 2013 at the authors' institution, with
      or without non-complex aortic surgery, were identified. Patients were excluded if
      AVR was not isolated, had occurred prior to July 1997, or if the initial AVR was
      performed before the patient was aged 18 years. All reoperations were performed
      through a full sternotomy. The main outcomes of interest were operative results
      and long-term survival. RESULTS: A total of 101 patients was identified, of which
      34 had undergone previous mini-AVR and 67 previous sAVR. The time from the
      previous AVR was similar in both groups (median 7.6 years overall). Of previous
      valve implants, 57 were bioprostheses and 44 mechanical; structural valve
      degeneration was the most common indication for surgery (43/101). Mini-AVR and
      sAVR patients did not differ significantly with regards to patient demographics
      and preoperative risk factors. A strong trend towards shorter skin-to-skin
      operative times was observed for mini-AVR (330 min versus 356 min; p = 0.053).
      Postoperatively, mini-AVR patients had a shorter ventilation time (5.7 h versus
      8.4 h; p = 0.005), intensive care unit stay (37 h versus 63 h; p <= 0.001) and
      hospital length of stay (6.5 days versus 8.0 days; p = 0.038). There was one
      operative mortality in the sAVR, and none in the mini-AVR group. Mid-term
      survival at one and five years for mini-AVR was 100% (95% CI 100-100) and 100%
      (95% CI 100-100), and for sAVR was 93.9% (95% CI 88.2-99.7) and 85.0% (95% CI
      75.1-94.9), respectively (p = 0.041). CONCLUSION: Mini-AVR confers benefits
      during subsequent reoperative AVR, with shorter hospital stays and improved long
      term survival. These findings suggest that mini-AVR should be considered for
      patients at risk for aortic valve reoperation, and describes a previously
      unreported advantage of this well-established technique.

PMID- 26204683
TI  - Aortic sutureless Perceval valve for small root in concomitant mitral valve
      replacement.
AB  - Conventional valves have a sewing ring that reduces the effective orifice area
      for a given valve size. In patients with small aortic roots, the implantation of
      a stented conventional prosthesis can be very difficult or may lead to patient
      prosthesis mismatch. In the case of the Sorin Perceval sutureless aortic valve,
      concomitant mitral valve replacement (MVR) is an exclusion criterion because the
      latter valve's rigid ring may interfere with the self-expandable stent anchorage
      of the Sorin Perceval sutureless valve, or cause it to become distorted. The case
      is reported of very small, 77-year-old woman with severe aortic valve stenosis,
      severe mitral regurgitation and asymmetric hypertrophy of the left ventricle with
      systolic anterior motion. The patient underwent MVR and concomitant off-label
      implantation of the Sorin Perceval S sutureless valve due to the extremely small
      size of the aortic annulus. Echocardiography performed on completion of surgery,
      at discharge from hospital and at after a four-month follow up, documented a
      normal mitral prosthesis position and function, a normal aortic prosthesis
      position, and mild central regurgitation in both valves.

PMID- 26204684
TI  - The effect of oxLDL on aortic valve calcification via the Wnt/ beta-catenin
      signaling pathway: an important molecular mechanism.
AB  - BACKGROUND AND AIM OF THE STUDY: Calcific aortic valve disease (CAVD) is a
      commonly acquired valvular disease. Although previous studies have shown valve
      calcification to be mediated by a chronic inflammatory disease process, with many
      similarities to atherosclerosis that included inflammatory cell infiltrates,
      lipoproteins, lipids, extracellular bone-matrix proteins, and bone minerals,
      little is known of the mechanisms of the cellular and molecular components and
      processes. It has recently been hypothesized that the calcific aortic valve is a
      product of active inflammation, similar to the atherosclerosis pathological
      process. Thus, the cessation of statin therapy should, in theory, have an effect
      on the treatment of CAVD and on aortic valve myofibroblasts (AVMFs), which play
      an important role in aortic valvular calcification. The study aim was to
      determine if oxidized low-density lipoprotein (oxLDL) could stimulate the
      apoptosis of AVMFs and the calcific-related pathway, and whether atorvastatin
      could inhibit the effects of AVMFs induced by oxLDL. The Wnt/GSK-3beta/beta
      catenin signaling pathway may play a key role in this process, thereby making a
      major contribution to aortic valve calcification. METHODS: AVMFs were
      successfully acquired using a combination of trypsin and collagenase enzyme
      digestion, and made phenotypic for the identification for alpha-smooth muscle
      actin (alpha-SMA). Cell apoptosis was monitored using flow cytometry, bone
      protein expression by Western blot, and related gene expression by reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: A positive
      identification of alpha-SMA, a myofibroblast marker, confirmed the successful
      harvesting of myofibroblasts. OxLDL significantly induced cell apoptosis (p <
      0.05), and this became even more obvious after 48 h (p < 0.01). OxLDL also
      significantly increased the protein expression of all differentiation markers (p
      < 0.05), as confirmed through Western blotting and RT-PCR, while atorvastatin
      significantly reduced the effects of oxLDL (p < 0.05). CONCLUSION: Among the
      mechanisms of the cellular and molecular components and processes, oxLDL
      increased the valve calcification-related signaling pathway by increasing
      extracellular bone-matrix protein that produces osteoblastic gene markers via the
      Wnt/GSK-3beta/beta-catenin pathway. And atorvastatin also prevented any oxLDL
      induced effects through the same pathway, this may represent a new therapeutic
      target for CAVD, as an alternative to traditional valve replacement surgery.

PMID- 26204686
TI  - Evaluation of the effect of percutaneous mitral balloon valvuloplasty on left
      ventricular systolic function via strain and strain rate in patients with
      isolated rheumatic mitral stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: Percutaneous balloon mitral valvuloplasty (PMBV)
      has an established role in the treatment of rheumatic mitral stenosis. The study
      aim was to evaluate the effects of PMBV on left ventricular function in patients
      with rheumatic mitral stenosis (MS) by using strain and strain rate imaging
      modalities. METHODS: The study included 30 consecutive patients (21 women, nine
      men; mean age 44 +/- 14 years) with moderate to severe MS. Left ventricular long
      axis strain and strain rate color tissue Doppler imaging of the septal, lateral,
      inferior and anterior basal segments were performed one day before and seven days
      after PMBV. RESULTS: Compared with pretreatment findings, lateral systolic strain
      (-13.4 +/- 2.9% versus -18.4 +/- 3.9%; p = 0.024), inferior systolic strain (
      14.7 +/- 2.3% versus -17.6 +/- 2.1%; p = 0.016), anterior systolic strain (-15.2
      +/- 2.4% versus -17.2 +/- 2.2%; p = 0.02), and septal systolic strain (-15.7 +/-
      1.6% versus -18.1 +/- 1.9%; p = 0.018) values were significantly increased after
      the procedure, but no significant change was observed in strain rate analysis.
      CONCLUSION: A rapid improvement in strain values after PMBV in patients with
      isolated MS showed that the LV systolic dysfunction in isolated MS is strongly
      associated with impaired. hemodynamic parameters. Significantly increased strain
      values can be added to the criteria of successful PMBV.

PMID- 26204685
TI  - Mid-term results for a patch valvuloplasty technique to correct posterior leaflet
      prolapse.
AB  - BACKGROUND AND AIM OF THE STUDY: Most valve repair techniques require resection
      and multiple sutures. In the present study, a novel technique without resection
      for correction of posterior leaflet prolapse due to chordal elongation or rupture
      was employed, the aim being to evaluate the outcomes of a non-resecting valve
      repair technique in patients with posterior leaflet prolapse that caused
      significant mitral regurgitation (MR). METHODS: Between May 2008 and December
      2010, a total of 90 consecutive patients with posterior leaflet prolapse (55
      males, 35 females; mean age 51.5 +/- 14.6 years) underwent patch valvuloplasty.
      The procedure involved suturing the free margin of the prolapsed leaflet,
      invagination of the folded leaflet tissue into the left ventricular side,
      coverage of the dimpled portion with a round bovine pericardial patch using a
      continuous suture technique, and reshaping of the posterior annulus using a 53-
      to 61-mm strip. All patients underwent postoperative echocardiography after a
      mean follow up of 41.9 +/- 10.4 months. RESULTS: No early death occurred, but
      there was one late death due to a non-cardiac cause. At the last
      echocardiographic follow up, 81 patients (90%) showed none or trace MR, seven
      (7.8%) had mild MR, and two (2.2%) moderate MR. The mean mitral valve area was
      2.4 +/- 0.5 cm2 and the mean pressure gradient 2.8 +/- 1.2 mmHg. No patient
      required reoperation due to recurrent or aggravated MR. CONCLUSION: In patients
      with posterior leaflet prolapse, the applied patch valvuloplasty technique was
      useful and reliable, showing excellent clinical and echocardiographic outcomes.
      Additional long-term evaluations with close follow up should be performed.

PMID- 26204687
TI  - Evaluation of prosthetic valve thrombosis by 64-row multi-detector computed
      tomography. .
AB  - BACKGROUND AND AIM OF THE STUDY: Multi-detector computed tomography (MDCT),
      combined with retrospective electrocardiographic gating, permits cardiac imaging
      with high accuracy. Recent advances in MDCT have seemed to respond adequately to
      the need for a non-invasive and reliable assessment of the coronary artery lumen.
      METHODS: Two patients with prosthetic aortic valves (one bioprosthetic, one
      mechanical) presented at the authors' institution with dyspnea and syncopal
      episodes. MDCT was performed to evaluate thrombus characteristics and exclude
      coronary artery disease (CAD). RESULTS: Based on the MDCT coronary artery
      assessment, neither patient underwent preoperative invasive coronary angiography,
      abolishing the risk of any iatrogenic thrombus fragmentation and subsequent
      embolization. One patient underwent surgical treatment without complications,
      while medical therapy was successful in the other case. CONCLUSION: MDCT can be
      used for the accurate imaging of thrombi on prosthetic aortic valves, and to
      correctly assess possible CAD.

PMID- 26204688
TI  - Aortic sutureless bioprosthesis implantation following degeneration of a SOLO
      stentless valve.
AB  - A case is presented of the early degeneration of a 21 mm SOLO stentless valve
      concomitant with severe mitral regurgitation (MR). Transcatheter valve-in-valve
      implantation was considered in this high-risk case (logistic EuroSCORE 29.3%),
      but was dismissed because of the risk of coronary occlusion, an absence of visual
      landmarks, and the impossibility to treat the MR. Following the implantation of a
      27 mm Medtronic Hancock II mitral bioprosthesis, the leaflets of the SOLO valve
      were removed, and a 19 mm 3f Enable sutureless bioprosthesis delivered into the
      remaining sewing belt of the stentless valve. The total cross-clamp time was 64
      min. No aortic paravalvular leakage was detected at discharge and early follow up
      (four months); the mean and peak transvalvular aortic gradients were 13 and 23
      mmHg, respectively, and the left ventricular ejection fraction 60%. A sutureless
      strategy simplified the management of this high-risk case.

PMID- 26204689
TI  - Transcatheter aortic valve-in-valve implantation for severe bioprosthetic
      stenosis after Bentall operation using a homograft in a patient with Behcet's
      disease.
AB  - A 43-year-old man presented with severe aortic stenosis. Eight years previously,
      he had undergone primary surgical aortic valve replacement (AVR) for severe
      aortic regurgitation, but one year later developed cardiac arrest and complete
      atrioventricular block as a result of non-bacterial thrombotic endocarditis with
      severe valvular dehiscence. Following the diagnosis of prosthetic valve failure
      caused by Behcet's disease, the patient underwent a Bentall operation using 23 mm
      aortic homograft with permanent pacemaker implantation and coronary artery bypass
      grafting. Subsequently, he was stable with steroid administration and
      azathioprine for seven years after the second operation, but recently suffered
      from severe dyspnea and chest pain. Echocardiography revealed the development of
      severe aortic stenosis. A preprocedural evaluation demonstrated a porcelain aorta
      with severe calcification in the previous homograft valve on computed tomography,
      and critical stenosis at the ostium of the left circumflex artery on coronary
      angiography. After percutaneous coronary intervention for the ostium of the left
      circumflex artery, a transcatheter AVR was successfully performed using a 26 mm
      Edwards SAPIEN XT valve. The patient recovered without any complications after
      the procedure. This is the first report of a successful transcatheter aortic
      valve-in valve implantation for severe homograft aortic stenosis after a Bentall
      operation, using a homograft, in a patient with Behcet's disease.

PMID- 26204690
TI  - Age-related reoperation rate after the Ross procedure: a report from the German
      Ross Registry.
AB  - BACKGROUND AND AIM OF THE STUDY: An increasing number of young adult patients are
      choosing bioprostheses for aortic valve replacement (AVR). In this context, the
      Ross operation deserves renewed consideration as an alternative biological
      substitute. After both the Ross procedure and bioprosthetic AVR, reoperation
      rates remain a concern and may be related to age at surgery. Herein are reported
      details of freedom from reoperation after the Ross procedure for different age
      groups. METHODS: The reoperation rates of 1,925 patients (1,444 males, 481
      females; mean age 41.2 +/- 15.3 years) from the German Ross registry with a mean
      follow up of 7.4 +/- 4.7 years (range: 0.00-18.51 years; total 12,866.6 patient
      years) were allocated to three age groups: group I < 40 years; group II 40-60
      years; and group III > 60 years. RESULTS: At 10 years (respectively 15 years) of
      follow up, freedom from reoperation was 86% (76%) in group I, 93% (85%) in group
      II, and 89% (83%) in group III. CONCLUSION: There is some evidence that, at least
      during the first 10 and 15 years after AVR, the Ross procedure provides a
      significantly lower reoperation rate in young adult and middle-aged patients aged
      < 60 years. This information may be of interest to the patients' or physicians'
      decision-making for aortic valve surgery.

PMID- 26204691
TI  - Patients with systemic lupus erythematosus and antiphospholipid syndrome
      undergoing cardiac valve surgery.
AB  - BACKGROUND AND AIM OF THE STUDY: Systemic lupus erythematosus (SLE) and
      primary/secondary antiphospholipid syndrome (APLS) may cause early degenerative
      changes in cardiac valves, such as Libman-Sacks endocarditis, though few reports
      exist of this condition. Herein are presented the early and late clinical
      outcomes after cardiac valve surgery in patients diagnosed with SLE and APLS in a
      single-center experience. METHODS: A prospective analysis was conducted of the
      perioperative and follow up data acquired from patients with diagnosed SLE, and
      primary and secondary APLS, who underwent either single or combined valve surgery
      at the authors' department between 2002 and 2014. RESULTS: Fifteen patients (14
      females, one male; mean age 53 +/- 16 years; range: 16-77 years) were identified.
      The mean follow up time was 49 +/- 32 months (range: 12.5-119 months). Thirteen
      patients (11 females, two males) were diagnosed with SLE; one of these patients
      had tricuspid Libman-Sacks endocarditis, while two female patients had primary
      APLS and four had secondary APLS. Besides bioprosthetic and mechanical valve
      replacements, mitral and tricuspid valve reconstruction were performed. The mean
      cross-clamp time was 112 +/- 73 min (range: 55-294 min). Early major
      cardiovascular events occurred in two patients, and late non-fatal events in four
      patients, including one thromboembolic event. The 30-day and in-hospital
      mortalities were both 0%. Currently, 12 patients (80%) are alive at the end of
      follow up. Actuarial survival was 92 +/- 7.4% at one year, 74 +/- 18% at four
      years, and 49 +/- 23% at ten years. CONCLUSION: Despite general concerns, the
      present results confirmed that patients with SLE and APLS can be operated on for
      cardiac valve disease, with favorable early results and acceptable long-term
      outcome.

PMID- 26204692
TI  - Coagulase-negative staphylococcus infective endocarditis in a lupus patient with
      Libman-Sacks endocarditis.
AB  - Libman-Sacks endocarditis is the most widely encountered aseptic endocarditis
      among patients with systemic lupus erythematosus. Due to the deformed cardiac
      valves, secondary infective endocarditis should be considered in lupus patients
      with acute refractory heart failure and fever of unknown origin. The case is
      reported of a woman with lupus and Libman-Sacks endocarditis who had concurrent
      coagulase-negative Staphylococcus infective endocarditis that resulted in
      cerebral septic emboli and acute pulmonary edema. She underwent valve replacement
      surgery for acute heart failure, and gradually recovered with antibiotic
      treatment.

PMID- 26204693
TI  - Comparison of aortic valve annulus diameter determination through 3-dimensional
      transesophageal echo with cardiac MDCT and assessment of predictors for annulus
      sizing.
AB  - OBJECTIVES: The long-term success of CoreValve stent prosthesis (Medtronic)
      implantation for severe aortic valve stenosis is limited in determination of
      correct aortic valve annulus. METHODS: We retrospectively investigated
      preinterventional cardiac 256-slice computed tomography (cardiac CT) scans and 3
      dimensional transesophageal echocardiography (3D TEE) for assessment of aortic
      valve annulus to (i) compare both methods as well as (ii) to define predictors
      for annulus sizing. RESULTS: We investigated 200 consecutive patients with a mean
      aortic valve annulus (AA) of 24mm and a mean age of 81 years. Primarily we
      defined mean diameters of AA individually and grouped the different patients
      according to age, gender, body weight, length, surface area and body mass index.
      Thereby, we found statistical significant different annulus diameter in age
      (larger diameter when < 80 years of age), gender (male > femal), and body length
      (larger diameter when length > 165cm). Secondly, the multivariate analysis
      demonstrated that the age, the gender and the body length were additionally
      independent predictors for annulus size. CONCLUSION: Our data demonstrate the
      feasibility of cardiac CT and 3D TEE with no difference in the quality of the
      aortic valve annulus diameter determination. We describe predictors for annulus
      size in age, gender and body length. Conclusive, we support patient dependent
      parameters as age, gender and body length as predictors that must go into
      selection of CoreValve stent prosthesis size individually prior to implantation
      procedure.

PMID- 26204694
TI  - Ross procedure in adults: is reoperation a real concern?
AB  - BACKGROUND AND AIM OF THE STUDY: Reintervention after the Ross procedure (RP)
      remains a concern. Hence, the study aim was to assess the long-term results of
      the RP in adults and to identify predictors of reoperation. METHODS: Between 1995
      and 2012, a total of 263 consecutive patients (189 males, 74 females; mean age 42
      +/- 14 years) underwent the RP, using the free-standing root technique. The mean
      follow up was 7.5 +/- 5.0 years and was 94% complete. Survival, and freedom from
      autograft, homograft and Ross-related reoperation were analyzed using Kaplan
      Meier analysis, while Cox proportional hazard regression was used to identify
      predictors of reoperation. RESULTS: Early mortality was 2.6% (n = 7) and late
      mortality 4.9% (n = 14). Survival at 13 years was 90% (95% CI 80-95%). Freedom
      from homograft, autograft and Ross-related reoperation at 13 years were 97% (95%
      CI 90-99%), 92% (95% CI 82-96%) and 90% (95% CI 81-95%), respectively. No
      predictors of homograft reoperation were identified. Freedom from autograft
      reoperation was not significantly different for patients with preoperative aortic
      insufficiency (AI) (88%; 95% CI 74-95% at 13 years) compared to those with aortic
      stenosis (96%; 95% CI 84-99% at 13 years), or both (86%; 95% CI 51-97% at 13
      years) (p = 0.62). Other variables (gender, aortic/pulmonary mismatch and aortic
      annulus diameter) were not significantly associated with the need for autograft
      reoperation. CONCLUSION: Despite its complexity and reoperation rate, RP should
      be considered as a valid surgical option for aortic valve disease treatment in
      selected patients. Among the present series, no predictors for homograft or
      autograft reoperation were identified.

PMID- 26204695
TI  - Feto-maternal outcomes of urgent open-heart surgery during pregnancy.
AB  - BACKGROUND AND AIM OF THE STUDY: Cardiac surgery during pregnancy is rarely
      required and potentially increases feto-maternal mortality. The study aim was to
      evaluate pregnancy outcomes in females who underwent open-heart surgery with
      cardiopulmonary bypass (CPB) during pregnancy. METHODS: Between 1999 and 2014, a
      total of 16 pregnant women (mean age 27 +/- 7 years; mean gestational age 13 +/-
      7.7 weeks) underwent urgent cardiac surgery using CPB. The preoperative diagnosis
      included prosthetic valve dysfunction in 12 women (five aortic, seven mitral),
      native valve endocarditis and critical aortic stenosis each in one woman, and
      intracardiac masses in two women. Eleven patients were in the first trimester,
      three in the second trimester, and two in the third trimester. A retrospective
      analysis was conducted that included maternal variables of age, gestational age,
      cardiac diagnosis, prior operations, surgical details, maternal morbidity and
      mortality and type of delivery, while fetal variables included incidence of low
      birth weight, prematurity, and fetal malformation. Patients were allocated to two
      groups: Group A (n = 9) included pregnant women with living neonates, while group
      B (n = 7) included pregnant women with an aborted fetus or dead neonate. All data
      were compared between the groups. RESULTS: There was no in-hospital maternal
      mortality. There were no significant differences between the two groups regarding
      age, gestational age, previous cardiac operation, type of surgery, duration of
      operation, perfusion pressure and core temperature during CPB. The CPB time was
      longer in group B (110.3 +/- 57.1 min) than in group A (62 +/- 15.7 min) (p =
      0.028), as was the aortic cross-clamp time (54.3 +/- 27.2 min and 38.7 +/- 9.3
      min in groups A and B, respectively) (p = 0.014). Group B patients received
      higher doses of inotropes perioperatively. No congenital abnormalities were
      identified in any of the living neonates. CONCLUSION: The durations of CPB and
      aortic cross-clamping may not affect maternal outcome, but shorter CPB and aortic
      cross-clamp times led to better fetal outcomes. Increasing the perioperative
      dosage of inotropes may lead to a reduced fetal survival.

PMID- 26204696
TI  - Surgery for a quadricuspid aortic valve: case report and comprehensive review of
      the literature.
AB  - Quadricuspid aortic valve (QAV) is a rare cardiac anomaly which can present with
      clinically significant regurgitation. The case is presented of a 38-year-old
      female patient with a regurgitant QAV managed surgically. A review of the current
      literature relating to QAV is also provided. The most common valve type that is
      operated on is type B, thus separating the surgical population from that of all
      QAVs, in which type A is most common. Moreover, aortic aneurysms were found to be
      a common and previously unrecognized significant characteristic among QAV
      patients. The majority of patients with a regurgitant QAV undergo replacement,
      although repairs have recently gained popularity. To date, the outcomes for both
      groups appear similar.

PMID- 26204697
TI  - Transcatheter aortic valve implantation in a patient with myelofibrosis and
      severe thrombocytopenia.
AB  - Transcatheter aortic valve implantation (TAVI) has been commonly used to treat
      patients with aortic stenosis who have a contraindication to, or a high risk of,
      corrective surgery. Anti-thrombotic treatment is an important part of the TAVI
      procedure to avoid thrombotic complications during both peri- and post-procedural
      periods. However, no specific data are available regarding the safety of TAVI
      with or without anti-thrombotic treatment, either during the surgical procedure
      or follow up period in patients with thrombocytopenia, such as myelofibrosis.
      Here, the case is reported of a patient with myelofibrosis and severe
      thrombocytopenia who underwent a TAVI procedure without anti-thrombotic treatment
      such as heparin, acetyl salicylic acid, or clopidogrel.

PMID- 26204698
TI  - Triple prosthetic valve dysfunction 30 years after surgery.
AB  - Triple prosthetic valve operation carries a high peri-procedural risk and is
      associated with decreased long-term survival. Herein is reported the case of a 59
      year-old female with a 30-year history of successful triple-valve replacement for
      rheumatic heart disease, who presented with symptomatic valvular dysfunction and
      rhythm disturbances. The patient was one of the few who had survived more than 30
      years after triple-valve surgery. Illustrative echocardiograms and
      cinefluoroscopic images are provided, and issues regarding prosthetic valve
      dysfunction and rhythm disturbance management in operated patients are briefly
      discussed.

PMID- 26204699
TI  - Papillary fibroelastoma involving chordae of the mitral valve with two aortic
      valve excrescences.
AB  - Among primary cardiac tumors, papillary fibroelastoma (PF) represents less than
      10% of all such lesions. Of these tumors, 90% are solitary and multiple tumors
      have rarely been reported. More than 75% of PFs are attached to heart valves,
      while tumors that originate in the non-valvular endocardium are rare. We report a
      case of PF originating from the chordae of the mitral valve with two concomitant
      aortic valve Lambl's excrescences.

PMID- 26204700
TI  - Why Embryos Should Not Be Off-Limits. Learning to alter their genes safely could
      prevent inherited diseases.

PMID- 26204702
TI  - Go Big or Go Home.

PMID- 26204701
TI  - Star Wars. Settling the fight over a telescope on a Hawaiian holy site.

PMID- 26204703
TI  - Sound Check. A 100-year ear debate comes to an end.

PMID- 26204704
TI  - Hacking Heats Up.

PMID- 26204705
TI  - Transfusion Solution.

PMID- 26204706
TI  - Facebook for the Ferocious.

PMID- 26204707
TI  - Blitzkrieg Basics.

PMID- 26204709
TI  - Build-a-Battery.

PMID- 26204708
TI  - First Impressions.

PMID- 26204710
TI  - Poised for Pluto.

PMID- 26204711
TI  - Can We Stop Aging?

PMID- 26204712
TI  - iResearch Subject.

PMID- 26204713
TI  - MYSTERY OF THE HIDDEN COSMOS.

PMID- 26204715
TI  - Life at Hell's Gate.

PMID- 26204714
TI  - WHAT DOESN"T KILL YOU....

PMID- 26204716
TI  - Out shining silicon.

PMID- 26204718
TI  - The Whole Universe Catalog.

PMID- 26204717
TI  - From wolf to dog.

PMID- 26204719
TI  - Outrageous. Why cops kill.

PMID- 26204720
TI  - True Size of Africa.

PMID- 26204721
TI  - Seizing the real opportunity presented by data breaches.

PMID- 26204722
TI  - What's the verdict on HIEs?

PMID- 26204723
TI  - Key considerations for document management.

PMID- 26204724
TI  - Three views on revenue cycle management.

PMID- 26204725
TI  - POC solutions to improve workflow, reduce errors and enhance patient experiences.

PMID- 26204726
TI  - The need for a common throughput language. Bringing balance to competing
      priorities.

PMID- 26204727
TI  - Beyond compliance HIPAA after Anthem.

PMID- 26204728
TI  - Trimming time and money.

PMID- 26204729
TI  - Three tips for conducting comprehensive workflow efficiency assessments.

PMID- 26204730
TI  - Secure texting integrated with EHRs.

PMID- 26204731
TI  - Achieving true quality improvement.

PMID- 26204732
TI  - [Analysis of the Rhythm of Atrial Epicardial Mapping Data Based on Dominant
      Frequency].
AB  - If heart function is normal, the atrial cells are excited in a stable rhythm. But
      this would change during atrial fibrillation. In this paper, after comparing with
      the method of characteristic point, we use the dominant frequency method to
      analyze the activation pattern under sinus and atrial fibrillation rhythm in
      different parts of atria based on epicardial mapping system. It is found that the
      activation rhythm changes a lot in different parts of atria, and the automaticity
      of atrial cells change obviously in somewhere. The result shows that dominant
      frequency method is very suitable for the analysis of atrial fibrillation signal.
      What's more, we also roughly discuss the role of this method in exploring the
      driving sources during atrial fibrillation.

PMID- 26204733
TI  - [Pulse Signal Quality Estimation and Filtering Based on Cyclostationary
      Algorithm].
AB  - In order to reduce the impact of various noise in pulse signal, the quality
      estimation and filtering algorithms based on cyclostationarity are proposed to
      reprocess pulse signal. First, A quality evaluation index of pulse signal which
      named quality factor is defined by cyclic spectrum to describe the quality
      variation of the pulse signal affected by noise; Second, a cyclic correlation
      matched filter (CCMF) is designed to remove noise. The simulation of pulse signal
      is produced by ourselves and noise signal is provided by MIT-BIH physiological
      database are used to test the function of proposed method, and then the method is
      applied to the actual pulse signal. The results show that the quality factor can
      accurately reflect the quality of the pulse signal and the CCMF can effectively
      remove noise from pulse signal.

PMID- 26204734
TI  - [Working Temperature Predication of Artificial Heart Based on Neural Network].
AB  - The purpose of this paper is to achieve a measurement of temperature prediction
      for artificial heart without sensor, for which the research briefly describes the
      application of back propagation neural network as well as the optimized, by
      genetic algorithm, BP network. Owing to the limit of environment after the
      artificial heart implanted, detectable parameters out of body are taken advantage
      of to predict the working temperature of the pump. Lastly, contrast is made to
      demonstrate the prediction result between BP neural network and genetically
      optimized BP network, by which indicates that the probability is 1.84% with the
      margin of error more than 1%.

PMID- 26204735
TI  - [Research of Electronic Sphygmomanometer Intelligent Aeration Based on Pulse Wave
      Identification].
AB  - Through various common domestic and foreign electronic sphygmomanometers to test
      blood pressure, we find that when measuring high blood pressure or low blood
      pressure, there is a mismatch between the maximum inflation pressure and the
      blood pressure measurement, which often results in repeatedly inflating and
      deflating as well as the problem of high inflation pressure. In order to solve
      these problems and find a suitable maximum inflation pressure, two intelligent
      pneumatic solutions based on identifying of pulse wave are suggested and 700
      groups of blood pressure experiments are done, then the two solutions are
      verified by experiments. The experiment proved that these solutions proposed have
      good stability and accuracy, they can solve the problems appeared in measuring
      blood pressure effectively, at the same time, the second solution that estimate
      the maximum inflation pressure during inflation is considered as the best one.

PMID- 26204736
TI  - [Analysis of Pulse Rate Variability and Its Application to Wearable Smart
      Devices].
AB  - In this paper, a reflection type photoelectric pulse wave sensor was designed for
      short-term pulse rate variability analysis. Photoplethysmography (PPG) signals
      and ECG signals (obtained with the Dimetek MicroECG recorder Dicare-m1CP) were
      recorded synchronously from 20 healthy subjects. The analytical results show a
      significant correlation (correlation coefficient r > 0.99) between the PPG
      derived peak-to-peak (PP) intervals and the ECG-derived RR intervals. Besides,
      there are no significant differences (P > 0.05) between the HRV measured by ECG
      and the PRV quantified by the PPG whether in time domain, frequency domain, or
      the Poincare plot parameters. The experimental results suggest that the PPG-based
      short-term PRV analysis can be consistent with the ECG-based HRV measurement in
      wearable smart devices.

PMID- 26204737
TI  - [Design and Implementation of the Multi-Channel Meridian Impedance Detector Based
      on Current Driving].
AB  - A multi-channel meridian impedance detector used to the 3D meridian visualization
      positioning is presented. The detector is designed with the four-electrode method
      based on current driving according to low impedance of the meridian. The detector
      consists of power-supply module, sinusoidal signal generator, voltage-controlled
      current source, isolation amplifiers, filter circuit, amplitude detectors and so
      on.

PMID- 26204738
TI  - [Design of Smart Care Tele-Monitoring System for Mother and Fetus].
AB  - OBJECTIVE: To study and design a maternal and fetal monitoring system based on
      the cloud computing and internet of things, which can monitor and take smart care
      of the mother and fetus in 24 h. METHODS: Using a new kind of wireless fetal
      monitoring detector and a mobile phone, thus the doctor can keep touch with
      hospital through internet. The mobile terminal was developed on the Android
      system, which accepted the data of fetal heart rate and uterine contraction
      transmitted from the wireless detector, exchange information with the server and
      display the monitoring data and the doctor's advice in real-time. RESULTS: The
      mobile phone displayed the fetal heart rate line and uterine contraction line in
      real-time, recorded the fetus' grow process. It implemented the real-time
      communication between the doctor and the user, through wireless communication
      technology. CONCLUSIONS: The system removes the constraint of traditional
      telephone cable for users, while the users can get remote monitoring from the
      medical institutions at home or in the nearest community at any time, providing
      health and safety guarantee for mother and fetus.

PMID- 26204739
TI  - [Development of Special Drive Pediatric Ventricular Assist Device].
AB  - This paper uses AVR16 SCM, programming to achieve the software of PWM (pulse
      width modulation) control of intelligent H bridge chip LMD18200 driver of high
      speed DC motor, makes special speed tablet, obtains speed signal of high speed
      for photocoupler PC817, through the A/D conversion and processing circuit, and
      realizes the LED LCD digital display speed scheme. The driver for the pediatric
      ventricular assist device has been used at the laboratory trial, has high
      performance and wide application prospect.

PMID- 26204740
TI  - [Current Development of Breast-Specific Gamma Imaging (BSGI) Technique].
AB  - Breast-Specific Gamma Imaging (BSGI) is an improved and optimizing nuclear
      medicine breast imaging technique on the basis of traditional gamma camera. It
      uses a high resolution, small field-of-view scintilla detector. The detector is
      designed with 3 073 individual detector crystals and 48 position-sensitive
      photomultiplier tubes. The FOV of detector is 15 cm x 20 cm, and optimal system
      resolution for breast imaging is 3 mm, can detect the diameter of only 2-3 mm
      small lesions. BSGI has better sensitivity in detecting subcentimetre or
      nonpalpable breast cancer. The sensitivity for the diagnosis of breast cancer is
      high, not influenced by the density of the breast tissue, implants, architectural
      distortion-or scars from prior surgery or radiation. So it is called a high
      resolution, small field-of-view breast-specific gamma camera.

PMID- 26204741
TI  - [Key Technology and Quantity Control of Wearable Medical Devices].
AB  - In recent years, because the wearable medical devices can indicate the health
      monitoring index of blood sugar, blood pressure, heart rate, oxygen content,
      temperature, respiration of the human body anytime and anywhere, can also be used
      for the treatment of various diseases, accompanied by the development of large
      data, which will bring a subversive revolution for the medical device industry.
      This paper introduces the development of wearable devices, key technical index of
      main products, and to make a preliminary study on its quantity control.

PMID- 26204742
TI  - [Detections of the Focal Regions Temperature for High Intensity Focused
      Ultrasound].
AB  - As a tumor thermal ablation technology in cancer therapy, HIFU (High Intensity
      Focused Ultrasound) has been developed rapidly in recent years. With the
      technology becoming more and more mature, it's clinical application is becoming
      more and more widely. In HIFU therapy, the high-intensity ultrasound energy is
      focused in the target tumor tissue, generating heat within very short time,
      causing coagulation necrosis, so that the effect of the treatment is achieved. To
      ensure safe and therapeutic efficacy, HIFU therapy needs to be properly monitored
      by medical imaging, and temperature in the target has to be precisely measured,
      this article is based on the current domestic and foreign detection methods of
      the focal region temperature.

PMID- 26204743
TI  - [Research for Modification of Medical Silicone Rubber Material].
AB  - This paper reviews and analyzes the modifications of silicone rubber, containing
      nanometer material tilling, plasma surface modification, surface grafting,
      mixture with bioactive substrates and bionic coating. At last, the author shows
      the prospect for the future development of silicone rubber modification.

PMID- 26204744
TI  - [The Development Research of Needle Medical Supplies].
AB  - By the research of the characteristics and market using situation of all needle
      medical supplies, this paper sums up their development trend to provide reference
      for medical practitioners or the classification management of needle medical
      supplies.

PMID- 26204745
TI  - [Research on Universal Standard System of Medical Device].
AB  - By research on the universal standards classification of medical device,
      according to their functions and scope of application, they are divided into two
      levels, universal standard architecture is proposed, to provide opinions and
      suggestions for standard system construction of medical devices.

PMID- 26204746
TI  - [Analysis of the National Quality Inspection for Medical Devices].
AB  - This paper analyses overall situation of the national quality inspection for
      medical devices in recent 13 years. The statistics cover the inspected varieties,
      sampling quantity and quality status. The achievements and suggestions are
      provided, which are helpful for future work.

PMID- 26204747
TI  - [Feasibility Research of Determined Oxygen Permeability of Finished Soft Contact
      Lens].
AB  - OBJECTIVE: A method for determined oxygen permeability (Dk) of finished soft
      contact lens. METHODS: Oxygen permeability(Dk) of 10 group finished soft contact
      lens was determined by polarographic method, and the values were linearly
      calibrated using the measured and established Dk values of the specified
      reference materials. RESULTS: Only one Dk value fell outside of the requirement
      of GB 11417.3-2012 tolerance for Dk (+/- 20%). CONCLUSION: It is great
      practicability when determined the oxygen permeability (Dk) of finished soft
      contact lens by polarographic method which were linearly calibrated using the
      measured and established Dk values of the specified equal thickness reference
      materials without the measured lens customized 4 different thickness.

PMID- 26204748
TI  - [Analysis of Adverse Events of Disposable Umbilical Cord Clamp].
AB  - To investigate and analysis the multiple medical adverse events about disposable
      umbilical cord clamp during clinical using in Zhejiang province, and put forward
      some opinions some suggestions to improve the processing technology, to
      strengthen the professional training of medical staff in medical institutions of
      umbilical cord clamp using, and to take precautions against more adverse events.

PMID- 26204749
TI  - [Exploring Current Problems and Corresponding Strategies for Evaluation of
      Innovative Medical Devices in China].
AB  - Through the analysis of the current status and problems of innovative medical
      devices evaluation, tnis paper discussed the strategies of evaluation, and
      ultimately raises the frame of evaluation, so as to provide reference for
      scientific evaluation of medical devices in China.

PMID- 26204750
TI  - [The Characteristics and Management of Medical Equipment Clinical Trials in
      Hospital].
AB  - In this paper, we analyse the general information of medical equipment clinical
      trials by clinical trial process management experience to elaborate the
      characteristics of the medical equipment clinical trials and the existent
      problems in our hospital in 10 years. We propose corresponding countermeasures to
      ensure the quality of medical tests, and improve the management of medical
      equipment clinical trials in hospital.

PMID- 26204751
TI  - [Application of POCT in Community Health Institutions].
AB  - In this paper, POCT detection technology which has been carried out in community
      health institutions is summarized and introduced. The paper has made the research
      on the existing resistance and urgent problem of POCT in the community. At the
      same time, the paper described the prospect of the development of POCT detection
      technology in community health institutions in view of the future.

PMID- 26204752
TI  - [Challenges Analysis and Strategic Consideration on Medical Equipment
      Maintenance].
AB  - Expounding the status of the current domestic medical equipment maintenance
      management, and puting forward the strategic thinking of medical maintenance for
      the challenges of equipment maintenance management in the hospital. This
      discussion can be performed to control the maintenance costs of hospital
      effectively, increase the income and social benefits of the hospital.

PMID- 26204753
TI  - [Methods for construction of transgenic plant expression vector: a review].
AB  - Construction of recombinant plasmid vector for gene expression is a key step in
      making transgenic plants and important to study gene function and plant genetic
      engineering. A right choice of gene construction method can be cost-effective and
      achieve more diverse recombinant plasmids. In addition to the traditional methods
      in construction of plant gene expression vectors, such as Gateway technology,
      three DNA method and one step cloning, a few novel methods have been developed in
      recent years. These methods include oligonucleotide synthesis-based construction
      of small fragment gene expression vectors via competitive connection;
      construction of small RNA expression vector using pre-microRNA; recombination
      fusion PCR method which inserts DNA fragments of multiple restriction sites into
      the target vector; and insertion of a DNA fragment into any region of a linear
      vector via In-Fusion Kit. Construction of complex vectors with many fragments
      uses sequence and ligation-independent cloning method, Gibson isothermal assembly
      or Golden Gate assembly. This paper summarizes our working experience in the area
      of recombinant vector construction and reports from others with an intention to
      disseminate ideas about currently widely used DNA recombination methods for plant
      transformation.

PMID- 26204754
TI  - [Recent advances in biosynthesis of 4-hydroxybenzaote].
AB  - 4-Hydroxybenzoate (4HBA) is an important chemical compound used for synthesis of
      liquid crystal. Production of 4HBA from renewable resources is an effective mean
      to solve problems such as environmental pollution and petroleum shortage. This
      review briefly introduces the chemical synthesis of 4HBA from oil compounds, and
      mainly describes the progress in 4HBA biosynthesis from renewable resources by
      plants and microorganisms. In most intriguing aspect of plant-based synthesis of
      4HBA is the appeal of directly synthesizing a chemical from CO2. However, the
      glucosylation system in plant cells converting 4HBA to glucose conjugates,
      causing the post treatment a problem. The recombinant microorganisms produce pure
      4HBA, but less efficient. A new strain of Microbulbifer has ability to naturally
      accumulate 4HBA from glucose. Elucidation of the metabolic pathways and
      regulation systems would improve 4HBA synthesis efficiency.

PMID- 26204755
TI  - [Genome editing of industrial microorganism].
AB  - Genome editing is defined as highly-effective and precise modification of
      cellular genome in a large scale. In recent years, such genome-editing methods
      have been rapidly developed in the field of industrial strain improvement. The
      quickly-updating methods thoroughly change the old mode of inefficient genetic
      modification, which is "one modification, one selection marker, and one target
      site". Highly-effective modification mode in genome editing have been developed
      including simultaneous modification of multiplex genes, highly-effective
      insertion, replacement, and deletion of target genes in the genome scale, cut
      paste of a large DNA fragment. These new tools for microbial genome editing will
      certainly be applied widely, and increase the efficiency of industrial strain
      improvement, and promote the revolution of traditional fermentation industry and
      rapid development of novel industrial biotechnology like production of biofuel
      and biomaterial. The technological principle of these genome-editing methods and
      their applications were summarized in this review, which can benefit engineering
      and construction of industrial microorganism.

PMID- 26204756
TI  - [Overexpression of connexin 43 in bone marrow mesenchymal stem cells in Xiao
      Meishan swines].
AB  - We studied the function of connexin 43 (Cx43) gene in Xiao Meishan swine bone
      marrow mesenchymal stem cells (BMSCs) resulting from overexpression. Cx43
      eukaryotic expression vector (pEGFP-Cx43) was constructed and transfected into
      BMSCs by nucleofector, after detecting the transfection efficiency; the
      expression of Cx43 was verified by RT-PCR, immunofluorescence and western
      blotting. Furthermore, we detected its cell cycle and apoptosis through flow
      cytometry. Our results show that pEGFP-Cx43 plasmid was successfully constructed,
      and green fluorescence in pEGFP-Cx43 transfected BMSCs was highly expressed with
      60% transfection efficiency. In transgenic Xiao Meishan swines BMSCs, the
      expression level of Cx43 mRNA and protein were up-regulated. Meanwhile, the
      ability of cell proliferation was significantly increased, and the apoptosis rate
      was significantly reduced. Taken together, Cx43 overexpression could promote the
      proliferation of Xiao Meishan swine's BMSCs and markedly reduce their apoptosis,
      which provides evidence for in vivo research.

PMID- 26204757
TI  - [Nonconserved hinge in Baeyer-Villiger monooxygenase affects catalytic activity
      and stereoselectivity].
AB  - Baeyer-Villiger monooxygenases (BVMOs) are important biocatalysts to synthesize a
      series of valuable esters and lactones. Based on protein sequence alignment and
      crystal structure analysis, a nonconserved hinge which linked NADPH domain and
      FAD domain was speculated to play an important role in substrate recognition and
      catalytic oxidation process. Cyclohexanone monooxygenase (CHMO) was selected as a
      model. Mutants obtained by homologous replacement of the whole hinge almost
      completely lost its original catalytic activity, demonstrating that the overall
      hinge structure was of great importance. Some significant sites were identified
      to greatly affect the catalytic activity and stereoselectivity by alanine
      scanning mutagenesis, accompanied by enzyme activity assessments and chiral
      kinetic resolutions. Altering K153 decreased the activity of the enzyme but
      enhanced the stereoselectivity. Changing L143 site reduced stereoselectivity but
      had little effect on enzyme activity. Mutation at L144 site dramatically weakened
      both activity and stereoselectivity. Subsequently, these corresponding sites in
      phenylacetone monooxygenase were also illustrated to follow a similar rule,
      revealing a universal importance of these sites in the BVMO family. These results
      expanded our understanding of the structure-activity relationship of these
      enzymes and provided more proofs for future directed evolution of BVMOs.

PMID- 26204758
TI  - [Combinational expression of geranylgeranyl diphosphate synthase and taxadiene
      synthase in Coprinopsis cinerea].
AB  - Taxa-4(5),11(12)-diene is the precursor for paclitaxel biosynthesis. The
      diterpenoid paclitaxel (marketed as Taxol), a plant secondary metabolite isolated
      from yew, is an effective drug widely used in the treatment of numerous cancers.
      However, further application of taxol has been restricted due to its low yield in
      plants and the difficulties in extraction. To increase the intact isoprene flux,
      we constructed the fusion gene plasmid pBgGGTS and individual cassette plasmid
      pBgGGgTS to enhance the expression levels of geranylgeranyl diphosphate synthase
      gene (ggpps) and a taxadiene synthase gene (ts) in Coprinopsis cinerea. These two
      plasmids were separately transformed into C. cinerea LT2 strain, resulting in
      several putative transformants. Putative transformants were determined by PCR
      technique, indicating that 5 out of 13 putative transformants transformed by
      pBgGGTS and 6 out of 13 putative transformants transformed by pBgGGgTS,
      respectively. Additionally, the Southern blotting analysis of these 10
      transformants confirmed that both ggpps and ts gene were stably integrated into
      the genome of C. cinerea. Crude extracts from each of the transformants were
      analyzed. There is no difference in the mycelium extracts among the wild-type LT2
      and two types of transformants. However, analysis of culture filtrates indicated
      that an additional GC peak was found at the retention time of 16.762 min which
      was absent in the wild type control. The mass fragmentation pattern of this peak
      had the same diagnostic ions with taxa-4(5),11(12)-diene. According to peak area,
      the amounts of taxa-4(5),11(12)-diene in each fermented broth were 44 ng/L
      (transformed with pBgGGgTS) and 30 ng/L (transformed with pBgGGTS), respectively.
      In conclusion, co-expression of the ggpps and ts gene could increase the
      taxadiene production in C. cinerea.

PMID- 26204759
TI  - [Construction and identification of HSV-1 vector vaccine carrying HIV-1 antigen].
AB  - To construct an HSV-1 vector vaccine carrying HIV-1 antigens, HIV-1 gp160, gag,
      protease and the expression elements were chained together, and then inserted
      into the internal inverted repeat sequence region of HSV-1 by bacterial
      artificial chromosome technology. Firstly, HIV-1 gp160 (including type B and C),
      gag and protease genes were cloned into pcDNA3 in series to generate the
      pcDNA/gBgp and pcDNA/gCgp, then the recombinant plasmids were transfected into
      293FT cells, and HIV-1 antigen was detected from transfected cells by Western
      blotting. Then the expression cassettes from pcDNA/gBgp and pcDNA/gCgp,
      comprising HIV-1 antigen genes and expression elements, were cloned into pKO5/BN
      to generate the shuttle plasmids pKO5/BN/gBgp and pKO5/BN/gCgp. The shuttle
      plasmids were electroporated into E. coli cells that harbor an HSV-BAC, the
      recombinant bacteria were screened, and the recombinant DNA was extracted and
      transfected into Vero cells. The recombinant virus was purified through picking
      plaques, the virus' DNAs were identified by Southern blotting; HIV-1 antigen was
      detected from the recombinant HSV-1 infected cells by Western blotting, and the
      virus' replication competent was analyzed. As the results, gp160 and gag proteins
      were detected from 293FT cells transfected with pcDNA/gBgp and pcDNA/gCgp by
      Western blotting. The recombinant bacteria were generated from the E. coli
      electroporated with pKO5/BN/gBgp or pKO5/BN/gCgp. The recombinant HSV was
      purified from the Vero cells transfected with the recombinant DNA, the unique DNA
      fragment was detected from the genome of recombination HSV by Southern blotting;
      gp120 and gp41 were detected from the infected cells by Western blotting, and the
      recombinant HSV retained replication competent in mammalian cells. The results
      indicate that the recombinant HSV carrying HIV-1 gp160, gag and protease genes
      was generated, the virus retains replication competent in mammalian cells, and
      could be used as a replicated viral vector vaccine.

PMID- 26204760
TI  - [Generation of human oocyte-like cell differentiation in vivo].
AB  - Oocyte-like cells (OLC) can be generated by stem cells after the induction and
      differentiation in vitro, and maturated when transplanted in vivo to improve the
      development potential. Human amniotic fluid stem cells (hAFSC) were cultured for
      10 days in porcine follicle fluid (pFF) that was extracted from the medium
      follicle with high levels of hormones and Bmp 15 protein. After the induction,
      the cell aggregates showed the germ cell-like cells and produced the germ cell
      marker oct4, and triggered epigenetic changes with high expression of methylation
      transferase gene dnmt3b. The cell aggregates were packaged into porcine theca
      folliculi to form grafts, which were then transplanted into mouse renal capsule.
      After one month of transplantation, the morphology of OLC from a graft was not
      only similar to oocytes, but also expressed the germ cells markers (oct4, nanog,
      stella, ifitm3, dazl, nanos3, bmp15, and gd9). The results demonstrate that the
      in vivo differentiation model was useful for OLC development.

PMID- 26204761
TI  - [Construction of novel thioredoxin fusion protein expression system and the
      production of recombinant Lf-CATH2].
AB  - The objective of this study was to construct an improved thioredoxin fusion
      protein expression system, and express the cathelicidin-derived peptide, Lf
      CATH2. The improved fusion vector Lf-CATH2-pET32alpha(-TS) was successfully
      constructed by firstly deleting the thrombin site and S tag from the pET-32alpha
      vector, then inserting the Lf-CATH2 plus a thrombin site instead. Afterwards, Lf
      CATH2 was expressed in Escherichia coli as fusion protein. After the cleavage by
      thrombin, Lf-CATH2 was released and subsequently separated using affinity
      chromatography. The antimicrobial activity of purified Lf-CATH2 was also
      examined. The improved expression vector significantly increased enzyme cleavage
      efficiency by 37%, and Lf-CATH2 could be expressed in high yield and maintain the
      biological activity. This novel thioredoxin fusion protein expression system
      enables a quick production of high-yield bioactive cationic peptides like
      cathelicidins.

PMID- 26204762
TI  - [Construction of recombinant human nerve growth factor (rh-beta-NGF) eukaryotic
      vector and its expression in HEK293 cells].
AB  - Human nerve growth factor (NGF) is a nerve cell growth regulation factor, which
      can provide nutrition for the neurons and promote the neurites outgrowth. In
      order to produce large-scale recombinant human nerve growth factor (rh-beta-NGF),
      we constructed a plasmid vector, which can stably express the rh-beta-NGF in the
      HEK293 cell lines. First, the plasmid of pCMV-beta-NGF-IRES-dhfr was constructed
      and transformed into HEK293 cells. Then MTX pressurized filter and limiting
      dilution methods were used to obtain monoclonal HEK293 cell lines. After stepwise
      reducing serum in culture media, the cells eventually adapted to serum-free
      medium and secreted rh-beta-NGF. SDS-PAGE analysis revealed that the expression
      product owned a molecular weight of about 13 kDa and a purity of more than 50%.
      The peptide mapping sequencing analysis demonstrated the sequences of rh-beta-NGF
      matched with the theoretical ones. Later we purified this protein by ion exchange
      and molecular sieve chromatograph. Finally, our experimental results exhibited
      that the recombinant cell lines can stably express rh-beta-NGF with a high
      efficiency of more than 20 pg/cell x day. In addition, this protein could
      successfully induce differentiation of PC12 cells. In summary, our recombinant
      HEK293 cells can express bio-active rh-beta-NGF with great efficiency and
      stability, which supply a valid basis to large-scale production of rh-beta-NGF.

PMID- 26204763
TI  - [Expression of sarco/endoplasmic reticulum Ca(2+)-ATPase from Bombyx mori by
      baculovirus expression system].
AB  - Sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) is responsible for transporting
      Ca2+ into the endoplasmic reticulum and maintaining a suitable calcium
      environment in cells. The suitable calcium environment created by BmSerca is
      vital for the growth and development of silkworm. With a large molecular weight
      and 10 transmembrane domains, Serca is very difficult to express in Escherichia
      coli expression system. In order to obtain recombinant Serca with biological
      activity, pFastBac Dual vector was used to construct a binary baculovirus
      expression vector for expressing egfp and serca in cells. After transfection and
      infection, EGFP and Serca were expressed successfully in BmN-SWU1 cell line.
      Fluorescent observation revealed that the expression patterns of EGFP and Serca
      in infected cells were the same. Western blotting analysis showed that the
      recombinant proteins were about to express in cells 48 h post infection and
      highly expressed 96 h post infection. Ca(2+)-ATPase activities assays were used
      to evaluate the enzyme activities of recombinant Serca and found that the enzyme
      activities increased significantly after infection. The obtained data showed that
      this binary baculovirus expression system can be successfully used to express
      Serca with biological activity. The expression of Serca protein with this system
      is useful for further research on the function of Serca.

PMID- 26204764
TI  - [Effect of oxygen-vectors on the production of epsilon-poly-L-lysine].
AB  - To enhance the production of epsilon-poly-L-lysine (epsilon-PL) by improving
      dissolved oxygen level of the fermentation system, different oxygen-vectors were
      added to broth and n-dodecane was screened as the best oxygen-vector. The best
      amount of n-dodecane was 0.5% (V/V) and the best time was at start of the
      fermentation. In a fed-batch fermentation in a 5 L bioreactor, epsilon-PL
      concentration reached a maximum of (30.8 +/- 0.46) g/L and the dry cell weight
      obtained was (33.8 +/- 0.29) g/L, increasing by 31.6% and 20.7% compared with the
      control group, respectively. This improvement can be related to 0.5% n-dodecane
      could maintain dissolved oxygen concentration > 32% of air concentration compared
      with 23.8% in epsilon-PL production phase, and the production of a main by
      product, poly-L-diaminopropionic acid, fell by 31%. These results indicated that
      the dissolved oxygen level in the broth was improved by adding n-dodecane, which
      can inhibit the by-product production and improve the biosynthesis of epsilon-PL.

PMID- 26204765
TI  - [The Mechanisms Determining Bristle Pattern in Drosophila melanogaster].
AB  - Macrochaetes (large bristles) are arranged on the drosophila head and notum in a
      specific bristle pattern. The number and positions of the macrochaetes forming
      the pattern are important species-specific characteristics, which are determined
      by a strict positioning of the proneural clusters in the in the imaginal disc
      ectoderm in the third instar larvae and prepupae. In turn, the positioning of
      proneural clusters depends on the distribution of the so-called prepattern
      factors, responsible for the bristle prepatterning. The current concept
      identifies the prepattern factors with the transcription factors that initiate
      the local expression of the achaete-scute complex (AS-C) genes. Expression of
      these genes confined to certain regions of the ectoderm is the particular factor
      that determines the macrochaete pattern on the adult fly body. The review
      considers and systematizes the data on establishment of the prepatterning as the
      final stage in the functioning of hierarchically organized molecular genetic
      system resulting in the local expression of AS-C genes in the ectoderm of
      imaginal discs.

PMID- 26204766
TI  - [Thymus Development in Early Ontogeny: A Comparative Aspect].
AB  - This review is dedicated to comparative analysis of the early stages of thymus
      ontogeny in fish, amphibians, and mammals. Morphological and molecular-genetic
      aspects of the formation of thymic stroma, colonization of this organ with T-cell
      progenitors, and interaction of different cell populations in the course of
      organogenesis are considered. Particular attention is given to the hematopoietic
      role of the thymus during embryogenesis and new data on the origin of T-cell
      progenitors. The hypothesis about the possible presence in the organ of a self
      sustaining population of stem cells, formed regardless of fetal hematopoiesis
      areas, is discussed.

PMID- 26204767
TI  - [Articulata and Ecdysozoa].
AB  - Science has accumulated to date such amounts of valuable and diverse information
      that no scientists can be encyclopedists (like those of the 17th and 18th
      centuries). Now every scientist is usually well informed only in one particular
      area and often needs consultations of other specialists. The current situation in
      biology is similar. In addition to evolutionary morphology, which represents
      fundamentals of zoology, there is a new, clearly cutting-edge and progressive
      area of studies, molecular genetics, which has already revealed many important
      general biological patterns. But the conclusions that follow from examining
      natural phenomena from this new point of view using new methods sometimes prove
      to be at odds with conventional notions. Considerable controversies have emerged
      on the phylogenetic position of the type Arthropoda. The peculiar features of the
      general body plan and the type of development of these animals seem to give
      evidence that they evolved from Annelida, with which they are often combined
      under the name Articulata. But attempts have been made to replace this concept by
      the idea that the clade Ecdysozoa, which includes Arthropods as well as such
      animals with low levels of organization as Nematoda and Priapulida, emerged early
      in the evolution of Bilateria. The main reason for combining the said animals in
      this clade is the fact that they have molts regulated with ecdysone; this point
      of view is supported by molecular genetic arguments. Although in this review this
      controversial problem is considered from the morphological point of view, the
      main purpose of the review is to emphasize the need to establish mutual
      understanding.between morphologists and molecular biologists and carefully find
      out the causes of the existing disagreements. Rather than ideological opponents,
      the two areas of science should be allies helping each other to solve complicated
      problems.

PMID- 26204768
TI  - [Analysis of the Localization of Fibrillarin and Sites of Pre-rRNA Synthesis in
      the Nucleolus-Like Bodies of Mouse GV Oocytes after Mild Treatment with
      Proteinase K].
AB  - Postnatal development of mammalian oocytes is accompanied by functional and
      structural remodeling of the nucleolar apparatus: the final stage of this process
      is the formation of large objects (up to 10 MUm in diameter) termed nucleolus
      like bodies (NLBs) in preovulatory GV oocytes. N LB material was shown to be
      essential for early embryonic development, but its composition is still
      uncharacterized. In the present study, the protein-binding dye fluorescein-5
      isothiocyanate (FITC) was used to show that proteins characterized by a high
      local concentration are essential NLB components in mouse GV oocytes. One of
      these proteins was able to be identified for the first time using a mild
      treatment of oocytes with proteinase K; the protein identified was fibrillarin, a
      factor of early pre-rRNA processing. Fibrillarin is present in the inner NLB mass
      of all oocytes capable of synthesizing rRNA; however, it is not colocalized with
      BrUTP microinjected into oocytes in order to identify transcribed ribosomal
      genes, in contrast to the "surface" fibrillarin. These observations imply the
      accumulation of nucleolar proteins not involved in ribosome biogenesis inside the
      NLB. All NLBs present in an individual nucleus of an NSN-type GV oocyte contain
      fibrillarin and are associated with active ribosomal genes. The results obtained
      in the present work demonstrate that proteinase K treatment of GV mouse oocytes
      allows for: (1) identification of "cryptic" proteins inside the densely packed
      NLB material and (2) the enhancement of oocyte image quality during BrUTP-based
      identification of rRNA synthesis sites but (3) not for the detection of active
      ribosomal genes in the inner mass of the NLB. The fluorescent dye FITC can be
      recommended for assessment of intracellular protein localization in the oocytes
      of all mammalian species.

PMID- 26204769
TI  - [Development of the Human Olfactory Bulbs in the Prenatal Ontogenesis: an
      Immunochistochemical Study with Markers of Presynaptic Terminals (anti-SNAP-25, 
      Synapsin-I, -Synaptophysin)].
AB  - We provide the data of the olfactory bulbs (OB) development in the human fetuses
      on the stages from 8 week to birth. Immunochistochemical markers of presynaptic
      terminals (anti-SNAP-25, -synapsin-I, -synaptophysin) were used to evaluate the
      maturation of the OB. Differentiation of the OB layers begins from periphery,
      which implicitly evidences that growth of the olfactory nerves fibers induses not
      only anatomical differentiation of the OB, but also differentiation of its
      functional layers. The sites of the developing glomerulus are revealed using the
      immunochistochemical prosedure on the stage before distinct glomerulus can be
      identified with common histological procedure. OB conductive system demonstrates
      immunoreactivity with the antibodies to the presynaptic proteins on the all
      stages from 10-11 weeks of fetus development. Four stages of the OB development
      are described. All functional layers of the OB are mature at the 22-weeks stage.
      Further differentiation of the OB neuroblasts, including lamina formation of the
      internal granular leyer, glomerular layer development, OB growth continue after
      20-22 weeks stage until 38-40 weeks of the fetus develoment. Patterns of the
      immunoreactivity with antibodies to SNAP-25, synapsin-I and synaptophysin are
      completely appropriate to those of adult's OB on the 38-40 weeks of the prenatal
      development. Complete maturity of the human OB is achived at 38-40 weeks of the
      prenatal development.

PMID- 26204770
TI  - [Expression of Cancer-Testis Antigens of Magea and Mageb Families in Mouse
      Embryonic Fibroblasts Cultured in vitro].
AB  - Cancer-testis antigens are expressed in the spermatogenic and cancer cells as
      well as in human and mouse pluripotent stem cells. However, the role of cancer
      testis antigens of Mage families in the regulation of cellular processes in
      embryonic cells is largely unknown. In the present study comparative quantitative
      analysis of the gene expression of Magea and Mageb families was performed in
      mouse embryonic somatic cells (mouse embryonic fibroblasts, MEFs), long-term
      cultured in vitro and exposed to factors that inhibit and stimulate
      proliferation. The analysis revealed low expression of cancer-testis antigens of
      Mage families and showed that a lower proliferative activity of MEF at late
      passages was accompanied by slight up-regulation of the Magea gene expression and
      down-regutation of Mageb gene expression. However, modulation of the activity of
      MEK/ERK-signaling pathway and DNA demethylation by 5-azacytidine had no
      significant effects on the expression of Magea and Mageb genes in M EFs. The most
      essential changes in the expression levels of Mageb and Magea genes were found
      only when MEFs were exposed to mitomycin C. In all experimental variants,
      predominantly cytoplasmic localization of Mage antigens was found in MEFs at the
      phase of DNA synthesis, as well as at other cell cycle phases. Presumably, in
      actively proliferating mouse embryonic somatic cells the antigens of Magea and
      Mageb families can act as co-activators in the regulation of cell proliferation
      and other cellular functions.

PMID- 26204771
TI  - [Hormonal Induction of In Vitro Maturation and Ovulation of Loach Oocytes and
      Obtaining Egg Cells Capable of Fertilization and Development].
AB  - Loach oocytes that have reached a definitive size and are surrounded by
      follicular envelopes are capable of maturation and ovulating under the effect of
      1 MUg/mL progesterone in 75% Leibovitz medium with 1 g/L sodium bicarbonate or
      with pH adjustment to 9.0 by 1 N sodium hydroxide. Inseminated eggs are developed
      until the stage of when adding 20% bovine serum to the incubation medium.
      Substitution of the bovine serum with 10-20% loach ovarian fluid or 20% carp
      ovarian fluid provides more complete development of inseminated eggs until the
      stage of prolarvae that pass to active nutrition.

PMID- 26204772
TI  - [Endophytic Bacteria in Microbial Drugs that Improve Plant Development (Review)].
AB  - In this review data on the possibility of using endophytic bacteria for improving
      crop yields and quality are discussed.

PMID- 26204773
TI  - [Biotechnological Applications of the Extremophilic Yeast Yarrowia lipolytica
      (Review)].
AB  - The review focuses on applications of Y. lipolytica that demonstrate the
      importance of this organism and the need for its further investigation and
      application in science and industry. The ability of this yeast species to adapt
      to various environmental conditions (including extremophilic), to grow on various
      substrates, and to synthesize useful products makes this strain very promising
      for biotechnological applications.

PMID- 26204774
TI  - [Investigation of Protein Translocation Sec-System with Heterologous Gene
      Expression in Shewanella oneidensis MR-1 Bacterium Cells].
AB  - A comparison of the primary structures of the protein translocation Sec-system
      proteins in the Shewanella oneidensis MR-1 and Escherichia coli bacteria was
      carried out. The process of translocation of recombinant pro-enteroxins (SEB and
      SEH) from Staphylococcus aureus and pro-streptavidin (SAV) from Streptomyces
      avidinii in the S. oneidensis MR-1 and E. coli cell periplasm was studied. It was
      demonstrated that these marker proteins are transferred into the periplasmic
      space of the S. oneidensis MR-1 transformant strain cells. The identity of N
      terminal amino acid sequences of mature recombinant SEB, SEH, and SAV proteins
      (generated during post-translation proteolysis of leader peptide by the Sec
      system both in E. coli and S. oneidensis MR-1) was established.

PMID- 26204775
TI  - [Determination of Azospirillum Brasilense Cells With Bacteriophages via
      Electrooptical Analysis of Microbial Suspensions].
AB  - The dependence-of changes in the electrooptical properties of Azospirillum
      brasilense cell suspension Sp7 during interaction with bacteriophage PhiAb-Sp7 on
      the number and time of interactions was studied. Incubation of cells with
      bacteriophage significantly changed the electrooptical signal within one minute.
      The selective effect of bacteriophage PhiAb on 18 strains of bacteria of the
      genus Azospirillum was studied: A. amazonense Ami4, A. brasilense Sp7, Cd, Sp107,
      Sp245, Jm6B2, Brl4, KR77, S17, S27, SR55, SR75, A. halopraeferans Au4, A.
      irakense KBC1, K A3, A. lipoferum Sp59b, SR65 and RG20a. We determined the limit
      of reliable determination of microbial cells infected with bacteriophage: - 10(4)
      cells/mL. The presence of foreign cell cultures of E. coli B-878 and E. coli XL-1
      did not complicate the detection of A brasilense Sp7 cells with the use of
      bacteriophage PhiAb-Sp7. The results demonstrated that bacteriophage (PhiAb-Sp7
      can be used for the detection of Azospirillum microbial cells via t
      electrooptical analysis of cell suspensions.

PMID- 26204776
TI  - [The Engineering of a Yarrowia lipolytica Yeast Strain Capable of Homologous
      Recombination of the Mitochondrial Genome].
AB  - None of the studied eukaryotic species has a natural system for homologous
      recombination of the mitochondrial genome. We propose an integrated genetic
      construct pQ-SRUS, which allows introduction of the recA gene from Bacillus
      subtilis into the nuclear genome of an extremophilic yeast, Yarrowia lipolytica.
      The targeting of recombinant RecA to the yeast mitochondria is provided by leader
      sequences (5'-UTR and 3'-UTR) derived from the SOD2 gene mRNA, which exhibits
      affinity to the outer mitochondrial membrane and thus provides cotranslational
      transport of RecA to the inner space of the mitochondria. The Y. lipolytica
      strain bearing the pQ-SRUS construct has the unique ability to integrate DNA
      constructs into the mitochondrial genome. This fact was confirmed using a tester
      construct, pQ-NIHN, intended for the introduction of the EYFP gene into the
      translation initiation region of the Y. lipolytica ND1 mitochondrial gene. The Y.
      lipolytica strain bearing pQ-SRUS makes it possible to engineer recombinant
      producers based on Y. lipolytica bearing transgenes in the mitochondrial genome.
      They are promising for the construction of a genetic system for in vivo
      replication and modification of the human mitochondrial genome. These strains may
      be used as a tool for the treatment of human mitochondrial diseases (including
      genetically inherited ones).

PMID- 26204777
TI  - [Quantitative Assessment of the Combined Effect of the Nitrogen Status, Light and
      Dehydration of Mycelium on Conidiation in Neurospora crassa].
AB  - We performed a quantitative assessment of the conidia yield in Neurospora crassa
      in response to treatment with different conidiation effectors. Depending on
      nitrogen source and intactness of nitrite reductase (NiR) and nitrate reductase
      (NR), light and dehydration affected the number of viable conidia produced by the
      ascomycete. In most variants of the nitrogen status, the combined action of light
      and dehydration synergistically increased the conidia yield. Conidiation in wild
      type cells cultivated on the medium with NH4Cl as a sole nitrogen source did not
      respond to light, whereas illumination of the same culture grown on NH4NO3- or
      NaNO3-containing medium stimulated the process of spore formation. In response to
      light exposure, conidia formation occurred in the same way in the nit-2 (no NR
      and NiR) and nit-6 (no NiR) mutants cultivated in the presence of NH4Cl, but
      differed greatly when grown on the medium with NH4NO3. The results obtained
      indicate the possibility that NR and NiR participate in the photoconidiation
      regulation (wild-type strain on the medium with secondary nitrogen source);
      however, they cannot be necessary because light-dependent stimulation of spore
      formation was observed in nit-2 and nit-6 mutants.

PMID- 26204778
TI  - [Antioxidant Effect on the Growth And Formation of Lipids in the Fungus Lentinus
      tigrinus Growing on Medium with Lignosulfonate].
AB  - The addition of an antioxidant (2-ethyl-6-methyl-3-hydroxypyridine hydrochloride)
      to a culture of the fungus Lentinus tigrinus growing on a medium with
      lignosulfonate inhibited growth and changed the composition of cell
      phospholipids. The ratio of lipid messengers also changed, the phosphatidic acid
      level decreased, and the content of phosphatidylinositol dramatically increased.
      The substitution of lignosulfonate with glucose and the addition of an
      antioxidant increased the biomass yield of L. tigrinus, as well as that of
      another fungus, Cunninghamella japonica, which was incapable of biodegrading the
      biopolymer. The obtained results indicate the specificity of growth processes in
      the presence of lignosulfonate and confirm the role of free radical oxidation
      reactions in the biodegradation of this biopolymer by L. tigrinus.

PMID- 26204779
TI  - [Antimicrobial Activity of Fungi Strains of Trichoderma from Middle Siberia].
AB  - The antibiotic activity in 42 strains of 8 species of the Trichoderma genus (T.
      asperellum, T. viride, T. hamatum, T. koningii, T. atroviride, T. harzianum, T.
      Citrinoviride, and T. longibrachiatum) isolated from different Siberian ecotops
      was studied. It was shown that these species differ in the degree of their
      antibacterial and antifungal activity. The chosen strain, T. citrinoviride TV4-1,
      exhibited high activity and a wide range of actions against the opportunistic and
      pathogenic fungi of the Aspergillus and Candida albicans genus; bacteria,
      including methicillin-resistant Staphylococcus aureus; and cancer cells.
      According to mass and I R spectrometry data and the spectrum of biological
      action, peptaibols are probably the most active compounds in the strain culture
      extracts.

PMID- 26204780
TI  - [Biologically Active Peptides Isolated from Dill Anethum graveolens L].
AB  - Peptide mixtures with molecular weights of 1000-2000 Da and in vivo membrano
      trophic activity against mouse hepatocyte culture at very low concentrations were
      isolated from dill Anethum graveolens L. leaves. It has been found that plant
      peptides in aqueous solution formed larger nanosized particles of approximately
      90 nm with a secondary structure mainly composed of beta-structures and random
      coil structures. We demonstrated that peptides isolated from A. graveolens in
      vitro at an ultra-low dosage affected the size of the area of pigmented cells of
      amphibian liver, which are analogous to Kupffer cells of the mammalian liver,
      using roller organotypic newt liver culture models.

PMID- 26204781
TI  - [A New Approach to the Depletion of Albumin and Immunoglobulin G from Human
      Serum].
AB  - The use of proteomic analysis to find potential diagnostic biomarkers is limited
      by the presence of serum albumin (HSA) and immunoglobulin (IgG) at high
      concentrations in patients' blood; these substances impede the detection of serum
      proteins with similar molecular weights. Recombinant HSA- and IgG-binding
      polypeptides are used as ligands in creating sorbents for complete removal of the
      proteins by affinity chromatography. The binding specificity of the sorbents for
      HAS and IgG is higher than that of the conventionally used antibodies. A
      composite sorbent enabling the depletion of HSA and IgG from serum by single-step
      affinity chromatography is obtained. The. developed sorbents were used to prepare
      serum for proteomic analysis.

PMID- 26204782
TI  - A Deathtrap While Mowing.

PMID- 26204783
TI  - Determination of Entrapment Victim Extrication Forces with and without Use of a
      Grain Rescue Tube.
AB  - The forces required to extricate a test mannequin from a grain mass when buried
      at different depths with and without a grain restraint system were determined.
      When there was no grain restraint system in place, the vertical force required to
      pull the mannequin from the grain when it was buried waist deep and to the
      underarms was 1259 and 1766 N (283 and 397 lb(f)), respectively. It increased to
      1584 N (356 lb(f)) (+26%) and 2153 N (484 lb(f)) (+22%), respectively, with the
      restraint in place due to the changes in grain properties brought about by the
      insertion of the rescue tube. It was concluded that the use of a grain restraint
      during extrication of a victim does not reduce the forces required and that
      forcefully pulling an entrapped victim, especially with mechanical assistance,
      with or without a grain restraint system could result in severe injuries and
      possible death due to the forces exerted on the victim. The authors recommend
      that these findings be incorporated into current grain extrication training for
      emergency first responders.

PMID- 26204784
TI  - Physical Characteristics of Farm Equipment Crash Locations on Public Roads in
      Tennessee.
AB  - Safety of farm equipment on public roadways has been the topic of much research
      for several years. With more farm equipment traveling on roadways, it will
      continue to be an important topic. The objective of this research project was to
      locate areas with high crash rates involving farm equipment (excluding other slow
      moving vehicles) and to identify similarities, if any, among those locations.
      Data collected from public crash report records obtained from the Tennessee
      Highway Patrol were entered into a geographic information system (GIS) database,
      so locations with high crash rates could be identified. Physical data, including
      number of lanes, presence and width of shoulders, presence of farm equipment
      warning signs, and other roadway information, were gathered for each location.
      Information contained within the public accident records was also considered,
      including time of day, weather conditions, and severity of the accident. This
      research revealed that most collisions involving farm equipment in Tennessee
      occur during the months of May, June, and October. More crashes occur on Mondays
      than other days of the week, with Sundays.having the fewest reported crashes.
      Typically, most collisions occur between 14:00 and 16:00 and when the weather is
      clear. Of 16 accident sites at locations with high crash frequencies in northwest
      Tennessee, 88% had grass shoulders that were 1.8 m wide or less. No sites had
      farm equipment warning signs posted, and 81% had no posted speed limits. Farm
      equipment collisions could be reduced through better driver education, proper
      sign posting, and wider shoulders.

PMID- 26204785
TI  - Validation of Self-Reported Power Take-Off Shielding Using On-Site Farm Audits.
AB  - Despite the substantial contribution of power take-off (PTO) entanglements to
      workplace morbidity and mortality among agricultural workers, the degree of
      proper PTO shielding on U.S. farms remains poorly characterized. Sampling from
      the New York data of the USDA National Agricultural Statistical Service (NASS),
      at least 200 each of dairy, livestock, crop, fruit, and vegetable farms were
      surveyed by phone to determine the extent of proper PTO shielding. In the same
      year, on-site audits were performed at 211 randomly selected New York livestock
      and dairy farms using a four-point scale to assess PTO shielding. Supplemental
      data were gathered on farm acreage, number of livestock, principal commodity, and
      operator experience. The phone survey data for livestock and dairy farms were
      then compared to the on-farm audit data. In the phone survey, 72.5% of farms
      reported having shields on all implements. The mean percentage of implements
      reported to be shielded was 90.2%. By on-farm audit, 10% of farms had all
      implements properly shielded, and the mean percentage of properly shielded
      implements was 56.7%, with shielding rates differing widely for different classes
      of implements. No significant predictors of PTO shielding were identified. The
      phone survey greatly overestimated proper PTO shielding rates when compared with
      the on-farm audits. These data suggest a lower level of proper shielding among
      farmers than is mandated by current industry safety standards. The results also
      identify a principal weakness of phone surveys in accurately assessing the true
      magnitude of on-farm risk for PTO entanglement.

PMID- 26204786
TI  - Creating a National Coalition to Address Tractor Overturn Fatalities.
AB  - Tractor overturns continue to be the leading cause of death on U.S. farms. While
      rollover protective structures (ROPS) are effective in preventing these
      fatalities, they are underutilized due to a number of barriers. Past programs in
      the U.S. and abroad have targeted this area of agricultural safety; however, a
      national program is not yet in place for U.S. farmers. This study seeks to build
      a national partnership to address tractor overturn fatalities by increasing the
      number of tractors with ROPS. A diverse, multisector steering committee has been
      organized and is working together using Whole System in a Room methods. This
      method brings together partners from nine stakeholder groups to identify and
      commit to a collaborative solution to the issue.

PMID- 26204787
TI  - Field Tests of a Tractor Rollover Detection and Emergency Notification System.
AB  - The objective of this research was to assess the feasibility of a rollover
      detection and emergency notification system for farm tractors using field tests.
      The emergency notification system was developed based on a tractor stability
      model and implemented on a mobile electronic device with the iOS operating
      system. A complementary filter was implemented to combine the data from the
      accelerometer and gyroscope sensors to improve their accuracies in calculating
      the roll and pitch angles and the roll and pitch rates. The system estimates a
      stability index value during tractor operation, displays feedback messages when
      the stability index is lower than a preset threshold value, and transmits
      emergency notification messages when an overturn happens. Ten tractor rollover
      tests were conducted on a field track. The developed system successfully
      monitored the stability of the tractor during all of the tests. The iOS
      application was able to detect rollover accidents and transmit emergency
      notifications in the form of a phone call and email when an accident was
      detected. The system can be a useful tool for training and education in safe
      tractor operation. The system also has potential for stability monitoring and
      emergency notification of other on-road and off-road motorized vehicles.

PMID- 26204788
TI  - Impact of Automation on Drivers' Performance in Agricultural Semi-Autonomous
      Vehicles.
AB  - Drivers' inadequate mental workload has been reported as one of the negative
      effects of driving assistant systems and in-vehicle automation. The increasing
      trend of automation in agricultural vehicles raises some concerns about drivers'
      mental workload in such vehicles. Thus, a human factors perspective is needed to
      identify the consequences of such automated systems. In this simulator study, the
      effects of vehicle steering task automation (VSTA) and implement control and
      monitoring task automation (ICMTA) were investigated using a tractor-air seeder
      system as a case study. Two performance parameters (reaction time and accuracy of
      actions) were measured to assess drivers' perceived mental workload. Experiments
      were conducted using the tractor driving simulator (TDS) located in the
      Agricultural Ergonomics Laboratory at the University of Manitoba. Study
      participants were university students with tractor driving experience. According
      to the results, reaction time and number of errors made by drivers both decreased
      as the automation level increased. Correlations were found among performance
      parameters and subjective mental workload reported by the drivers.

PMID- 26204789
TI  - The EGR2 gene is involved in axonal Charcot-Marie-Tooth disease.
AB  - BACKGROUND AND PURPOSE: A three-generation family affected by axonal Charcot
      Marie-Tooth disease (CMT) was investigated with the aim of discovering genetic
      defects and to further characterize the phenotype. METHODS: The clinical, nerve
      conduction studies and muscle magnetic resonance images of the patients were
      reviewed. A whole exome sequencing was performed and the changes were
      investigated by genetic studies, in silico analysis and luciferase reporter
      assays. RESULTS: A novel c.1226G>A change (p.R409Q) in the EGR2 gene was
      identified. Patients presented with a typical, late-onset axonal CMT phenotype
      with variable severity that was confirmed in the ancillary tests. The in silico
      studies showed that the residue R409 is an evolutionary conserved amino acid. The
      p.R409Q mutation, which is predicted as probably damaging, would alter the
      conformation of the protein slightly and would cause a decrease of gene
      expression. CONCLUSIONS: This is the first report of an EGR2 mutation presenting
      as an axonal CMT phenotype with variable severity. This study broadens the
      phenotype of the EGR2-related neuropathies and suggests that the genetic testing
      of patients suffering from axonal CMT should include the EGR2 gene.

PMID- 26204790
TI  - Bronchiolitis obliterans syndrome due to donor-specific HLA-antibodies.
AB  - Chronic lung allograft dysfunction (CLAD) is a limiting factor for long-term
      survival in lung transplant recipients. Donor-specific human leukocyte antigen
      (HLA)-antibodies (DSA) have been suggested as potential risk factors for CLAD.
      However, their impact on clinical outcome following lung transplantation remains
      controversial. We performed a single-center study of 120 lung transplant
      recipients transplanted between 2006 and 2011. Patient sera were investigated
      before and after transplantation. The sera were screened by means of Luminex((r))
      technology (Luminex Inc., Austin, TX, USA) for IgG-HLA-class I and class II
      antibodies (ab). Using single antigen beads, DSA were identified and correlated
      retrospectively with clinical parameters. After transplantation 39 out of 120
      patients (32.5%) were positive for HLA-ab. The incidence of de novo DSA formation
      was 27 of 120 patients (22.5%). Eleven of 27 (41%) of de novo DSA-positive
      patients developed BOS compared to 13 of 93 (14%) DSA-negative patients (p =
      0.002). Furthermore, the generation of de novo DSA was independently associated
      with the development of BOS in multivariable analysis [hazard ration (HR) 2.5,
      95% confidence interval (CI) 1.0-6.08; p = 0.046). Our results indicate that de
      novo DSA are associated with the development of BOS after lung transplantation.
      Monitoring of HLA-ab after transplantation is useful for identifying high-risk
      patients and offers an opportunity for early therapeutic intervention. 

PMID- 26204791
TI  - Mycosis fungoides bullosa associated with bullous pemphigoid.

PMID- 26204792
TI  - Multivalent meningococcal serogroup B vaccines: challenges in predicting
      protection and measuring effectiveness.
AB  - Vaccines targeting Neisseria meningitidis serogroup B (MenB) have been attempted
      for 40 years. Monovalent outer membrane vesicle vaccines targeted at epidemic
      outbreaks have been successfully developed. Newer vaccines aim to induce
      antibodies to cross-reactive antigens, such as factor H binding protein (rLP2086)
      or a mix of outer membrane vesicle, factor H binding protein and other minor
      antigens (4CMenB). The true protective coverage among circulating MenB isolates
      afforded by these vaccines is unknown. Carefully conducted Phase IV post
      implementation evaluations designed to measure specific effectiveness against
      major circulating MenB clonal lineages are needed to address the critical
      question of which antigens are linked to protection. Progress with whole-genome
      sequencing and bio-informatics may allow the composition of antigen mozaics based
      on two major outer membrane proteins: PorA and FetA. 

PMID- 26204793
TI  - Gut Bifidobacterium microbiota in one-month-old Brazilian newborns.
AB  - Gut colonisation with bifidobacteria in early infancy is essential for the well
      being of the infant. Gestational age and mode of delivery are among the factors
      influencing the colonisation process. The aim was to characterise the
      bifidobacterial composition in the gut of one-month-old full-term and pre-term
      Brazilian infants, both being delivered vaginally or by caesarean section. Fourty
      nine Brazilian (Vicosa, Minas Gerais state) one-month-old infants were divided in
      two groups: full-term (n = 24) and pre-term (n = 25), and compared to each other.
      Each group was then characterised according to its mode of delivery. Infant stool
      samples were available for bifidobacterial characterisation by quantitative
      polymerase chain reaction (qPCR) method. All study infants were colonised by
      bifidobacteria. Bifidobacterium longum colonised all full-term and pre-term
      newborns. Differences were observed in counts of Bifidobacterium genus and
      Bifidobacterium longum between full-term and pre-term infants (8.8 log cells/g,
      IQR 7.9-9.1 vs. 7.1 log cells/g, IQR 6.6-8.6, p = 0.02 and 8.3 log cells/g, IQR
      6.7-9.1 vs. 6.4 log cells/g, IQR 6.1-6.7, p = 0.001, respectively). Furthermore,
      the prevalence of Bifidobacterium lactis differed between pre-term caesarean and
      pre-term vaginally born infants (50.0% vs. 93.8%, p = 0.023). Gut bifidobacterial
      composition of one-month-old full-term infants differs from that of pre-term
      newborns in Vicosa, Minas Gerais state, Brazil. Gestational age is a factor
      influencing bacterial numbers and species, while mode of delivery have an impact
      on the prevalence and quantity of bifidobacteria in studied infants.
      Bifidobacteria may have an impact on later health of the infants and the species
      B. longum and B. lactis might provide clues on the potential probiotic
      applications in pre-term newborns at the risk of developing postnatal
      complications. 

PMID- 26204794
TI  - cfxA expression in oral clinical Capnocytophaga isolates.
AB  - Capnocytophaga spp. are commensal bacteria involved in oral and systemic
      diseases, with a variable susceptibility to beta-lactams. The cfxA gene
      expression level was assessed using quantitative RT-PCR, and reasons of the
      observed misexpression were discussed, as insertion of foreign genetic material,
      contributing to dissemination and evolution of antibiotic resistance genes. 

PMID- 26204795
TI  - Association between Down syndrome and mortality in young children with critical
      illness: a propensity-matched analysis.
AB  - AIM: To evaluate the outcomes among critically ill young children with Down
      syndrome using propensity score matching from a national database. METHODS:
      Patients in the age group from one day through 24 months admitted to an intensive
      care unit during their hospital stay at a Pediatric Health Information System
      (PHIS)-participating hospital (2004-2013) were included. RESULTS: Of the 293,697
      patients who qualified for inclusion, 12,282 (4%) were classified in the Down
      syndrome group. Using propensity score matching, 10,477 patients with Down
      syndrome were matched one to one to patients without Down syndrome. Prior to
      matching, the mortality was significantly lower among the patients with Down
      syndrome (with vs. without Down syndrome, odds ratio (OR), 0.74; 95% confidence
      interval (CI), 0.69-0.79; p < 0.001). After matching, the mortality was similar
      in both groups (OR, 0.96; 95% CI, 0.87-1.07; p = 0.51). The mortality risk
      increased among the Down syndrome patients with increasing hospital length of
      stay (LOS). CONCLUSION: In this large, contemporary cohort, Down syndrome did not
      confer a significantly higher mortality risk among children with critical
      illness. However, children with Down syndrome followed a time-dependent,
      differential mortality risk with increased risk noted in relation to increasing
      hospital LOS.

PMID- 26204796
TI  - Phylogenetic investigation of the complex evolutionary history of dispersal mode
      and diversification rates across living and fossil Fagales.
AB  - As a primary determinant of spatial structure in angiosperm populations, fruit
      dispersal may impact large-scale ecological and evolutionary processes. Essential
      to understanding these mechanisms is an accurate reconstruction of dispersal mode
      over the entire history of an angiosperm lineage. A total-evidence phylogeny is
      presented for most fossil fruit and all extant genera in Fagales over its c. 95
      million yr history. This phylogeny - the largest of its kind to include plant
      fossils - was used to reconstruct an evolutionary history directly informed by
      fossil morphologies and to assess relationships among dispersal mode,
      biogeographic range size, and diversification rate. Reconstructions indicate four
      transitions to wind dispersal and seven to biotic dispersal, with the
      phylogenetic integration of fossils crucial to understanding these patterns.
      Complexity further increased when more specialized behaviors were considered,
      with fluttering, gliding, autorotating, and scatter-hoarding evolving multiple
      times across the order. Preliminary biogeographic analyses suggest larger range
      sizes in biotically dispersed lineages, especially when pollination mode was held
      constant. Biotically dispersed lineages had significantly higher diversification
      rates than abiotically dispersed lineages, although transitions in dispersal mode
      alone cannot explain all detected diversification rate shifts across Fagales. 

PMID- 26204797
TI  - Recent developments in 2D layered inorganic nanomaterials for sensing.
AB  - Two dimensional layered inorganic nanomaterials (2D-LINs) have recently attracted
      huge interest because of their unique thickness dependent physical and chemical
      properties and potential technological applications. The properties of these
      layered materials can be tuned via both physical and chemical processes. Some 2D
      layered inorganic nanomaterials like MoS2, WS2 and SnS2 have been recently
      developed and employed in various applications, including new sensors because of
      their layer-dependent electrical properties. This article presents a
      comprehensive overview of recent developments in the application of 2D layered
      inorganic nanomaterials as sensors. Some of the salient features of 2D materials
      for different sensing applications are discussed, including gas sensing,
      electrochemical sensing, SERS and biosensing, SERS sensing and photodetection.
      The working principles of the sensors are also discussed together with examples. 

PMID- 26204798
TI  - Diagonal gaits in the feathertail glider Acrobates pygmaeus (Acrobatidae,
      Diprotodontia): Insights for the evolution of primate quadrupedalism.
AB  - Research on primate origins has revolved around arboreality and, more
      specifically, the adaptations that are linked to safe navigation in the fine
      branch niche. To this end, extant non-primate mammals have been used as models to
      assess the significance of these adaptations. However, the size of these models
      is larger than that estimated for early primates. In contrast, the feathertail
      marsupial glider Acrobates pygmaeus, with a body mass of 12 g, a clawless
      opposable hallux, and terminal branch feeding habits appears more suited to
      modeling behavioral adaptations to the small branch milieu. Analysis of video
      recordings of 18 feathertail gliders walking on poles of variable diameter and
      inclination revealed that they preferentially used diagonal sequence gaits, fast
      velocities and low duty factors. Diagonal gaits did not correlate to duty factor,
      but increased as substrate size decreased, and from descending to ascending
      locomotion. Furthermore, the duty factor index increased in more diagonal gaits
      and ascending locomotion. Finally, velocities were lower on smaller substrates,
      and were mainly regulated by stride frequency and, to a lesser degree, stride
      length. Feathertail glider gaits displayed noteworthy behavioral convergences
      with primate quadrupedalism, but some of these results need additional
      investigation. Despite any discrepancies, these features appear to be favorable
      for quadrupedal progression on small branches, providing a selective advantage
      for navigating within a fine branch niche and highlighting the importance of
      small body size in early primate evolution.

PMID- 26204800
TI  - [Urine antigen testing: Indication and contribution to the treatment of community
      acquired pneumonia].
AB  - Urinary antigen tests are quick and simple tests helping to provide an
      etiological diagnosis in community-acquired pneumonia. However, their
      prescription is sometimes excessive and performed in unjustified situations. The
      therapeutic benefit is limited. Indeed, studies show that appropriate antibiotic
      therapy based on the result of urinary antigen tests does not improve the cost
      and the patient survival compared to empirical antibiotic therapy. One must be
      careful before antibiotic therapy reduction based on the sole negative result of
      urinary antigen test. Legionella urinary antigen test is the most commonly method
      used for the diagnosis of legionellosis but must be prescribed in a specific
      clinical context. Streptococcus pneumoniae urinary antigen test is especially
      interesting in the epidemiological surveillance of pneumococcal community
      acquired pneumonia. 

PMID- 26204799
TI  - The BDNF Valine 68 to Methionine Polymorphism Increases Compulsive Alcohol
      Drinking in Mice That Is Reversed by Tropomyosin Receptor Kinase B Activation.
AB  - BACKGROUND: The valine 66 to methionine (Met) polymorphism within the brain
      derived neurotrophic factor (BDNF) sequence reduces activity-dependent BDNF
      release and is associated with psychiatric disorders in humans. Alcoholism is one
      of the most prevalent psychiatric diseases. Here, we tested the hypothesis that
      this polymorphism increases the severity of alcohol abuse disorders. METHODS: We
      generated transgenic mice carrying the mouse homolog of the human Met66BDNF
      allele (Met68BDNF) and used alcohol-drinking paradigms in combination with viral
      mediated gene delivery and pharmacology. RESULTS: We found that Met68BDNF mice
      consumed excessive amounts of alcohol and continued to drink despite negative
      consequences, a hallmark of addiction. Importantly, compulsive alcohol intake was
      reversed by overexpression of the wild-type valine68BDNF allele in the
      ventromedial prefrontal cortex of the Met68BDNF mice or by systemic
      administration of the tropomyosin receptor kinase B agonist, LM22A-4.
      CONCLUSIONS: Our findings suggest that carrying this BDNF allele increases the
      risk of developing uncontrolled and excessive alcohol drinking that can be
      reversed by directly activating the BDNF receptor, tropomyosin receptor kinase B.
      Importantly, this work identifies a potential therapeutic strategy for the
      treatment of compulsive alcohol drinking in humans carrying the Met66BDNF allele.

PMID- 26204802
TI  - Complexes of a naphthalimide photoacid with organic bases, and their excited
      state dynamics in polar aprotic organic solvents.
AB  - Complex formation and intermolecular excited-state proton transfer (ESPT) between
      a dihydroxy-1,8-naphthalimide photoacid and organic bases are investigated in
      polar aprotic solvents. First, quantum chemical calculations are used to explore
      the acid-base and spectroscopic properties and to identify energetically
      favorable complexes. The two hydroxyl groups of the photoacid enable stepwise
      formation of 1 : 1 and 1 : 2 complexes. Weak bases exhibit only hydrogen-bonding
      interactions whereas strong bases are able to deprotonate one of the hydroxyl
      groups resulting in strong negative cooperativity (K1? 4K2) in the formation of
      the 1 : 2 complex. Time-resolved fluorescence studies of the complexes provide
      strong indications of a three-step dissociation process. The species involved in
      the model are: a hydrogen-bonded complex, a hydrogen-bonded ion pair, a solvent
      separated ion pair, and a free ion pair. 

PMID- 26204801
TI  - Childhood maltreatment modifies the relationship of depression with hippocampal
      volume.
AB  - BACKGROUND: Childhood maltreatment (CM) may modify the relationship between major
      depressive disorder (MDD) and hippocampal volume reduction. To disentangle the
      impact of MDD and CM on hippocampal volume we investigated the association
      between MDD and hippocampal volume in persons with and without a history of CM in
      two independent cohorts. METHOD: We used data of 262 participants from the
      Netherlands Study of Depression and Anxiety (NESDA) (mean age 37 years, 32% male)
      and 636 participants from the SMART-Medea study (mean age 61 years, 81% male). In
      both studies a 12-month diagnosis of MDD and CM were assessed using a diagnostic
      interview. Hippocampal volume was measured in NESDA using FreeSurfer software on
      3-T magnetic resonance (MR) images and in SMART it was manually outlined on 1.5-T
      MR images. With analysis of covariance adjusted for intracranial volume, age,
      gender and lifestyle factors we estimated the effects of MDD and CM on
      hippocampal volume. RESULTS: In both cohorts CM was not significantly associated
      with hippocampal volume. After pooling the data MDD was associated with smaller
      hippocampal volume (B = -138.90 mm(3), p = 0.05) and the interaction between MDD
      and CM reached significance (p = 0.04); in participants with CM, MDD was related
      to smaller hippocampal volume (NESDA: B = -316.8 mm(3), p = 0.02; SMART: B = 
      407.6, p = 0.046), but not in participants without CM (p > 0.05). CONCLUSIONS:
      Our study shows that in two independent cohorts, particularly in individuals with
      CM, a diagnosis of MDD is related to smaller hippocampal volume. Prospective
      studies are needed to further determine through which mechanism CM may amplify
      the relationship between MDD and hippocampal volume.

PMID- 26204804
TI  - Is there convergence in the molecular pathways underlying the repeated evolution
      of sociality in African cichlids?
AB  - Despite wide variation in the complexity of social interactions across taxa, the
      basic behavioral components of sociality appear to be modulated by conserved
      hormone pathways. Specifically, the nonapeptide hormones oxytocin and vasopressin
      and their receptors have been implicated in regulating diverse social behaviors
      across vertebrates. Here, we took advantage of the repeated evolution of
      cooperative breeding in African cichlids to investigate whether there are
      consistent brain gene expression patterns of isotocin and arginine vasotocin
      (teleost homologues of oxytocin and vasopressin), as well as their receptors,
      between four closely related pairs of social (cooperative) and non-social (non
      cooperative) species. We first found that the coding sequences for the five genes
      studied were highly conserved across the eight species. This is the first study
      to examine the expression of both isotocin receptors, and so we performed a
      phylogenetic analysis that suggests that these two isotocin receptors are
      paralogues that arose during the teleost genome duplication. When we then
      examined brain gene expression patterns relative to social system, we found that
      there were whole-brain gene expression differences between the social and non
      social species in many of the species pairs. However, these relationships varied
      in both the direction and magnitude among the four species pairs. In conclusion,
      our results suggest high sequence conservation and species-specific gene
      expression patterns relative to social behavior for these candidate hormone
      pathways in the cichlid fishes. 

PMID- 26204803
TI  - Morphological and molecular genetic characterization of three Capillaria spp.
      (Capillaria anatis, Capillaria pudendotecta, and Capillaria madseni) and
      Baruscapillaria obsignata (Nematoda: Trichuridae: Capillariinae) in avians.
AB  - Morphological and genetic analyses were performed on four avian species of the
      subfamily Capillariinae (Nematoda: Trichuridae), i.e., Capillaria anatis from
      chickens (Gallus gallus domesticus) in Japan and the Philippines, Baruscapillaria
      obsignata from chickens and captive swans (Cygnus olor and Cygnus atratus) in
      Japan, Capillaria pudendotecta from captive swans in Japan, and Capillaria
      madseni from carrion and jungle crows (Corvus corone and Corvus macrorhynchos) in
      Japan. Although morphometric variations of male and female worms from different
      hosts and/or localities made the species identification difficult, the 18S
      ribosomal RNA gene (rDNA) sequences clarified their taxonomic position and
      phylogenetic relationships. Species of the same genus clustered robustly into a
      single clade in the phylogenetic tree based on the 18S rDNA, demonstrating to the
      extent possible the validity of the latest classification of the subfamily
      following Moravec's rearrangement in 1982. Male worms of C. pudendotecta are
      described here for the first time. 

PMID- 26204805
TI  - Duration of oral contraceptive use predicts women's initial and subsequent
      subjective responses to sexual stimuli.
AB  - Recent work suggests that a woman's hormonal state when first exposed to visual
      sexual stimuli (VSS) modulates her initial and subsequent responses to VSS. The
      present study investigated whether women's initial hormonal state was related to
      their subjective ratings of VSS, and whether this relationship differed with VSS
      content. We reanalyzed previously collected data from 14 naturally cycling (NC)
      women and 14 women taking oral contraceptives (OCs), who subjectively rated VSS
      at three hormonal time-points. NC women's ratings of 216 unique sexual images
      were collected during the menstrual, periovulatory, and luteal phases of their
      menstrual cycles, and OC women's ratings were collected at comparable time-points
      across their pill-cycles. NC women's initial hormonal state was not related to
      their ratings of VSS. OC women's initial hormonal state predicted their ratings
      of VSS with minimal contextual information and of images depicting female-to-male
      oral sex. Specifically, women who entered the study in the third week of their
      pill-cycle (OC-3 women) rated such images as less attractive at all testing
      sessions than did all other women. OC-3 women were also the only women to rate
      decontextualized VSS as unattractive at all testing sessions. These results
      corroborate previous studies in which women's initial hormonal state was found to
      predict subsequent interest in sexual stimuli. Future work, with larger samples,
      should more directly investigate whether OC-3 women's negative assessment of
      specific types of VSS reflects a reaction to the laboratory environment or a
      broader mechanism, wherein OC women's sexual interests decrease late in their
      pill-cycle. 

PMID- 26204806
TI  - Intrinsically disordered proteins drive membrane curvature.
AB  - Assembly of highly curved membrane structures is essential to cellular
      physiology. The prevailing view has been that proteins with curvature-promoting
      structural motifs, such as wedge-like amphipathic helices and crescent-shaped BAR
      domains, are required for bending membranes. Here we report that intrinsically
      disordered domains of the endocytic adaptor proteins, Epsin1 and AP180 are highly
      potent drivers of membrane curvature. This result is unexpected since
      intrinsically disordered domains lack a well-defined three-dimensional structure.
      However, in vitro measurements of membrane curvature and protein diffusivity
      demonstrate that the large hydrodynamic radii of these domains generate steric
      pressure that drives membrane bending. When disordered adaptor domains are
      expressed as transmembrane cargo in mammalian cells, they are excluded from
      clathrin-coated pits. We propose that a balance of steric pressure on the two
      surfaces of the membrane drives this exclusion. These results provide
      quantitative evidence for the influence of steric pressure on the content and
      assembly of curved cellular membrane structures. 

PMID- 26204807
TI  - A failure modes and effects analysis study for gynecologic high-dose-rate
      brachytherapy.
AB  - PURPOSE: To improve the quality of our gynecologic brachytherapy practice and
      reduce reportable events, we performed a process analysis after the failure modes
      and effects analysis (FMEA). METHODS AND MATERIALS: The FMEA included a
      multidisciplinary team specifically targeting the tandem and ring brachytherapy
      procedure. The treatment process was divided into six subprocesses and failure
      modes (FMs). A scoring guideline was developed based on published FMEA studies
      and assigned through team consensus. FMs were ranked according to overall and
      severity scores. FM ranking >5% of the highest risk priority number (RPN) score
      was selected for in-depth analysis. The efficiency of each existing quality
      assurance to detect each FM was analyzed. RESULTS: We identified 170 FMs, and 99
      were scored. RPN scores ranged from 1 to 192. Of the 13 highest-ranking FMs with
      RPN scores >80, half had severity scores of 8 or 9, with no mode having severity
      of 10. Of these FM, the originating process steps were simulation (5), treatment
      planning (5), treatment delivery (2), and insertion (1). Our high-ranking FM
      focused on communication and the potential for applicator movement. Evaluation of
      the efficiency and the comprehensiveness of our quality assurance program showed
      coverage of all but three of the top 49 FMs ranked by RPN. CONCLUSIONS: This is
      the first reported FMEA process for a comprehensive gynecologic brachytherapy
      procedure overview. We were able to identify FMs that could potentially and
      severely impact the patient's treatment. We continue to adjust our quality
      assurance program based on the results of our FMEA analysis.

PMID- 26204808
TI  - Marine metagenomics as a source for bioprospecting.
AB  - This review summarizes usage of genome-editing technologies for metagenomic
      studies; these studies are used to retrieve and modify valuable microorganisms
      for production, particularly in marine metagenomics. Organisms may be cultivable
      or uncultivable. Metagenomics is providing especially valuable information for
      uncultivable samples. The novel genes, pathways and genomes can be deducted.
      Therefore, metagenomics, particularly genome engineering and system biology,
      allows for the enhancement of biological and chemical producers and the creation
      of novel bioresources. With natural resources rapidly depleting, genomics may be
      an effective way to efficiently produce quantities of known and novel foods,
      livestock feed, fuels, pharmaceuticals and fine or bulk chemicals. 

PMID- 26204809
TI  - Pituitary abscess resulting in isolated abducens palsy.

PMID- 26204810
TI  - Solution-Processed Phosphorescent Organic Light-Emitting Diodes with Ultralow
      Driving Voltage and Very High Power Efficiency.
AB  - To realize power efficient solution-processed phosphorescent organic light
      emitting diodes (s-PhOLEDs), the corresponding high driving voltage issue should
      be well solved. To solve it, efforts have been devoted to the exploitation of
      novel host or interfacial materials. However, the issues of charge trapping of
      phosphor and/or charge injection barrier are still serious, largely restraining
      the power efficiency (PE) levels. Herein, with the utilization of an exciplex
      forming couple 4, 4', 4"-tris[3-methylphenyl(phenyl)amino]triphenylamine (m
      MTDATA) and 1,3,5-tri(m-pyrid-3-yl-phenyl)benzene (TmPyPB), the efficient charge
      injection and transporting, barrier-free hole-electron recombination for the
      formation of the interfacial exciplex, and elimination of charge traps of
      phosphors in the emissive layer are realized simultaneously, resulting in a turn
      on voltage of 2.36 V, a record high PE of 97.2 lm W(-1), as well as extremely low
      driving voltage of 2.60 V at 100 cd m(-2), 3.03 V at 1000 cd m(-2) and 4.08 V at
      10000 cd m(-2). This report is the first time that the PE performance of s-PhOLED
      approaches 100 lm W(-1) high level, even superior to the corresponding state-of
      the-art performance of the same color vacuum-deposited PhOLED (v-PhOLED)
      counterpart. We anticipate this report opens a new avenue for achieving power
      efficient monochromatic and white s-PhOLEDs with simple structures.

PMID- 26204811
TI  - Pyridine Based Fluorescence Probe: Simultaneous Detection and Removal of Arsenate
      from Real Samples with Living Cell Imaging Properties.
AB  - Pyridine based fluorescence probe, DFPPIC and its functionalized Merrifield
      polymer has been synthesized, characterized and used as an arsenate selective
      fluorescence sensor. Arsenate induced fluorescence enhancement is attributed to
      inter-molecular H-bonding assisted CHEF process. The detection limit for arsenate
      is 0.001 MUM, much below the WHO recommended tolerance level in drinking water.
      DFPPIC can detect intracellular arsenate in drinking water of Purbasthali, West
      Bengal, India efficiently. Graphical Abstract DFPPIC and its Merrifield conjugate
      polymer are used for selective determination and removal of arsenate from real
      drinking water samples of Purbasthali, a highly arsenic contaminated region of
      West Bengal, India. DFPPIC is very promising to imaging arsenate in living cells.

PMID- 26204812
TI  - Physicochemical Characterization and In Vitro Cytotoxic Effect of 3
      Hydroxyflavone in a Silver Nanoparticles Complex.
AB  - The aim of this work was to characterize the physico-chemical properties of 3
      hydroxyflavone (3-HF) in a silver nanoparticles complex (SNPs) using UV-vis and
      Fluorescence spectroscopy, Atomic Force Microscopy (AFM) and Transmission
      Electron Microscopy (TEM) analysis. One also evaluated its effect on the cell
      viability and morphology of L929 mouse fibroblast cells in vitro. The
      contribution of the carrier protein, Bovine Serum Albumin (BSA) to 3-HF
      properties has also been investigated. 3-HF in BSA/SNPs systems presented no
      cytotoxic effect in L929 mouse fibroblast cells at any of the tested
      concentrations. The results are discussed with relevance to the oxidative stress
      process. 

PMID- 26204813
TI  - Unhealthy diet practice and symptoms of stress and depression among adolescents
      in Pasir Gudang, Malaysia.
AB  - BACKGROUND/OBJECTIVE: Missing main meals and an unhealthy snacking pattern can
      lead to poor diet quality and consequently to the presence of chronic diseases
      among which mental disorder is no exception. Since there is little research on
      diet, skipping meals and psychological status in Asian countries, this study
      tries to determine eating behaviour and predicting symptoms of stress and
      depression of adolescents in Pasir Gudang, Malaysia. SUBJECTS AND METHODS: A
      cross-sectional study was conducted among Form 1 secondary school-going
      adolescents (n 1565, response rate: 90%) in southern Malaysia from April to May
      2013. A self-administered structured and validated questionnaire (socio
      demographic, eating behaviour questionnaire, and depression, anxiety and stress
      scales (DASS-21)) was used for data collection. RESULTS: Among respondents, 803
      (51.3%) were female, 1125 were Malay (71.9%) with a mean age of 13.7 (SD=0.8)
      years. Logistic regression analysis indicated that students who were underweight
      (OR=3.07, 95% CI 1.21, 7.76), obese (OR=2.64, 95% CI 1.01, 6.87), used to eat out
      of home (OR=1.37, 95% CI 1.28, 2.13), eat dinner (>4 days/week) (OR=1.59, 95% CI
      1.04, 2.43) were more likely to have depression or stress symptoms. Moreover,
      participants with 4-7 days/week eating breakfast (OR=0.88, 95% CI 0.21, 0.89)
      were less likely to be at mild/moderate stress. CONCLUSIONS: Findings underscore
      the effect of unhealthy eating practices among adolescents on mental health.
      Targeted education should be implemented to improve psychological well-being.

PMID- 26204814
TI  - Identification and function of an evolutionarily conserved signaling intermediate
      in Toll pathways (ECSIT) from Crassostrea hongkongensis.
AB  - Evolutionarily conserved signaling intermediate in Toll pathways (ECSIT) is a
      multifunctional adaptor protein that plays a key role in the regulation of the
      oxidative phosphorylation (OXPHOS) system, bone morphogenetic protein (BMP)
      pathway and Toll-like receptor (TLR) signaling pathway in mammals. However, the
      function of ECSIT homologs in mollusks, the second most diverse group of animals,
      is not well understood. In this study, we identified an ECSIT homolog in the Hong
      Kong oyster Crassostrea hongkongensis (ChECSIT) and investigated its biological
      functions. The full-length cDNA of ChECSIT is 1734 bp and includes an open
      reading frame (ORF) of 1074 bp that encodes a polypeptide of 451 amino acids. The
      predicted ChECSIT protein shares similar structural characteristics with other
      known ECSIT family proteins. Quantitative real-time PCR analysis revealed that
      ChECSIT mRNA is broadly expressed in all of the examined tissues and at different
      stages of embryonic development; its transcript level could be significantly up
      regulated by challenge with microorganisms (Vibrio alginolyticus, Staphylococcus
      haemolyticus and Saccharomyces cerevisiae). In addition, ChECSIT was found to be
      located primarily in the cytoplasm, and its overexpression stimulated the
      transcriptional activity of an NF-kappaB reporter gene in HEK293T cells. These
      findings suggest that ChECSIT might be involved in embryogenesis processes and
      immune responses in C. hongkongensis.

PMID- 26204815
TI  - Graphene mobility mapping.
AB  - Carrier mobility and chemical doping level are essential figures of merit for
      graphene, and large-scale characterization of these properties and their
      uniformity is a prerequisite for commercialization of graphene for electronics
      and electrodes. However, existing mapping techniques cannot directly assess these
      vital parameters in a non-destructive way. By deconvoluting carrier mobility and
      density from non-contact terahertz spectroscopic measurements of conductance in
      graphene samples with terahertz-transparent backgates, we are able to present
      maps of the spatial variation of both quantities over large areas. The
      demonstrated non-contact approach provides a drastically more efficient
      alternative to measurements in contacted devices, with potential for aggressive
      scaling towards wafers/minute. The observed linear relation between conductance
      and carrier density in chemical vapour deposition graphene indicates dominance by
      charged scatterers. Unexpectedly, significant variations in mobility rather than
      doping are the cause of large conductance inhomogeneities, highlighting the
      importance of statistical approaches when assessing large-area graphene transport
      properties. 

PMID- 26204816
TI  - New treatment strategies for pulmonary sarcoidosis: antimetabolites, biological
      drugs, and other treatment approaches.
AB  - About half of patients with sarcoidosis will need systemic therapy for their
      disease. Oral glucocorticoids are the standard first-line treatment for
      sarcoidosis. With time, patients might develop substantial morbidity from long
      term use of high doses of these drugs. We propose a step-wise approach to the
      management of pulmonary disease in sarcoidosis and provide details about how and
      when to use alternatives to glucocorticoids. The antimetabolites, such as
      methotrexate, azathioprine, leflunomide, and mycophenolate, are often used as
      alternatives to steroids. For patients who cannot be treated with low-dose
      glucocorticoids and an antimetabolite, anti-tumour necrosis factor (TNF)
      monoclonal antibodies have been shown to control disease. Unfortunately, anti-TNF
      drugs are associated with substantial toxic effects and in some cases are
      ineffective. The next step in treatment includes new strategies such as
      rituximab. A new regimen combining four antibiotics (levofloxacin, ethambutol,
      azithromycin, and rifamycin) has shown some promise in preliminary studies;
      however, the mechanism of action is unknown. Non-inflammatory effects of
      sarcoidosis, such as pulmonary hypertension and bronchiectasis, might also
      contribute to an increase in pulmonary symptoms. In those cases, alternative
      treatment strategies have to be considered. 

PMID- 26204817
TI  - Bidirectional modulation of anxiety-related and social behaviors by amygdala
      projections to the medial prefrontal cortex.
AB  - The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) modulate
      anxiety and social behaviors. It remains to be elucidated, however, whether
      direct projections from the BLA to the mPFC play a functional role in these
      behaviors. We used optogenetic approaches in behaving mice to either activate or
      inhibit BLA inputs to the mPFC during behavioral assays that assess anxiety-like
      behavior and social interaction. Channelrhodopsin-2 (ChR2)-mediated activation of
      BLA inputs to the mPFC produced anxiogenic effects in the elevated plus maze and
      open field test, whereas halorhodopsin (NpHR)-mediated inhibition produced
      anxiolytic effects. Furthermore, activation of the BLA-mPFC pathway reduced
      social interaction in the resident-intruder test, whereas inhibition facilitated
      social interaction. These results establish a causal relationship between
      activity in the BLA-mPFC pathway and the bidirectional modulation of anxiety
      related and social behaviors. 

PMID- 26204818
TI  - EGFR signaling upregulates surface expression of the GluN2B-containing NMDA
      receptor and contributes to long-term potentiation in the hippocampus.
AB  - N-methyl-d-aspartate receptors (NMDARs) have been known to be regulated by
      various receptor tyrosine kinases. Activation of epidermal growth factor receptor
      (EGFR) specifically increases NMDAR-mediated currents and enhances long-term
      potentiation (LTP) in the hippocampus. However, the mechanism through which EGFR
      regulates NMDARs remains to be elucidated. In this study we found that EGFR was
      highly expressed in the hippocampus and mainly localized in the non-synaptic
      region including the soma and neurites of cultured hippocampal neurons. EGFR
      activation led to an increase in ifenprodil-sensitive NMDAR currents. Consistent
      with this, we also observed that surface expression of GluN2B-containing NMDAR
      was upregulated. Our biochemical data from hippocampal slices and hippocampal
      cultured neurons demonstrated that EGF treatment in vitro significantly increased
      phosphorylation of the GluN2B subunit at Y1472 with a coincidental activation of
      Src family kinases (SFKs). EGFR blockade with a specific antagonist BIBX-1382
      attenuated an increase of GluN2B in the postsynaptic density during high
      frequency stimulation (HFS)-induced LTP. Moreover, BIBX blockade significantly
      impaired HFS-induced LTP. In conclusion, our findings suggest that EGFR signaling
      upregulates NMDARs through modification of the GluN2B subunit, and is required
      for HFS-induced LTP in the hippocampus. 

PMID- 26204819
TI  - Influx of extracellular Zn(2+) into the hippocampal CA1 neurons is required for
      cognitive performance via long-term potentiation.
AB  - Physiological significance of synaptic Zn(2+) signaling was examined in the CA1
      of young rats. In vivo CA1 long-term potentiation (LTP) was induced using a
      recording electrode attached to a microdialysis probe and the recording region
      was locally perfused with artificial cerebrospinal fluid (ACSF) via the
      microdialysis probe. In vivo CA1 LTP was inhibited under perfusion with CaEDTA
      and ZnAF-2DA, extracellular and intracellular Zn(2+) chelators, respectively,
      suggesting that the influx of extracellular Zn(2+) is required for in vivo CA1
      LTP induction. The increase in intracellular Zn(2+) was chelated with
      intracellular ZnAF-2 in the CA1 1h after local injection of ZnAF-2DA into the
      CA1, suggesting that intracellular Zn(2+) signaling induced during learning is
      blocked with intracellular ZnAF-2 when the learning was performed 1h after ZnAF
      2DA injection. Object recognition was affected when training of object
      recognition test was performed 1h after ZnAF-2DA injection. These data suggest
      that intracellular Zn(2+) signaling in the CA1 is required for object recognition
      memory via LTP. Surprisingly, in vivo CA1 LTP was affected under perfusion with
      0.1-1MUM ZnCl2, unlike the previous data that in vitro CA1 LTP was enhanced in
      the presence of 1-5MUM ZnCl2. The influx of extracellular Zn(2+) into CA1
      pyramidal cells has bidirectional action in CA1 LTP. The present study indicates
      that the degree of extracellular Zn(2+) influx into CA1 neurons is critical for
      LTP and cognitive performance. 

PMID- 26204820
TI  - Zoledronic acid suppresses metastasis of esophageal squamous cell carcinoma cells
      through upregulating the tight junction protein occludin.
AB  - We have previously demonstrated the radio-sensitizing effect of zoledronic acid
      (ZOL), a third generation bisphosphonate, on human esophageal squamous cell
      carcinoma (ESCC) cells. Here we show that ZOL suppresses metastatic progression
      of ESCC cells mainly through up-regulating the tight junction protein occludin.
      Exposure to ZOL at lower concentrations dramatically reduced migration and
      invasion of ESCC cells. In addition, ZOL treatment decreased the expression of
      mesenchymal markers, vimentin and N-cadherin, while increased the expression of
      the tight junction protein occludin. Moreover, ectopic expression of Slug, a well
      known transcriptional repressor of occludin, partially but significantly
      abrogated the effect of ZOL on occludin expression and subsequently rescued the
      malignant metastatic phenotype, suggesting that Slug is one of the mediators
      underlying the anti-metastatic effect of ZOL. The present study is the first to
      report the significance of ZOL on ESCC metastasis. These data are promising for
      the future application of this drug regimen in patients with ESCC. 

PMID- 26204822
TI  - 14th World Congress on Public Health in Kolkata, India.

PMID- 26204821
TI  - Antimicrobial agent triclosan is a proton ionophore uncoupler of mitochondria in
      living rat and human mast cells and in primary human keratinocytes.
AB  - Triclosan (TCS) is an antimicrobial used widely in hospitals and personal care
      products, at ~10 mm. Human skin efficiently absorbs TCS. Mast cells are
      ubiquitous key players both in physiological processes and in disease, including
      asthma, cancer and autism. We previously showed that non-cytotoxic levels of TCS
      inhibit degranulation, the release of histamine and other mediators, from rat
      basophilic leukemia mast cells (RBL-2H3), and in this study, we replicate this
      finding in human mast cells (HMC-1.2). Our investigation into the molecular
      mechanisms underlying this effect led to the discovery that TCS disrupts
      adenosine triphosphate (ATP) production in RBL-2H3 cells in glucose-free,
      galactose-containing media (95% confidence interval EC50 = 7.5-9.7 um), without
      causing cytotoxicity. Using these same glucose-free conditions, 15 um TCS dampens
      RBL-2H3 degranulation by 40%. The same ATP disruption was found with human HMC
      1.2 cells (EC50 4.2-13.7 um), NIH-3 T3 mouse fibroblasts (EC50 4.8-7.4 um) and
      primary human keratinocytes (EC50 3.0-4.1 um) all with no cytotoxicity. TCS
      increases oxygen consumption rate in RBL-2H3 cells. Known mitochondrial
      uncouplers (e.g., carbonyl cyanide 3-chlorophenylhydrazone) previously were found
      to inhibit mast cell function. TCS-methyl, which has a methyl group in place of
      the TCS ionizable proton, affects neither degranulation nor ATP production at non
      cytotoxic doses. Thus, the effects of TCS on mast cell function are due to its
      proton ionophore structure. In addition, 5 um TCS inhibits thapsigargin
      stimulated degranulation of RBL-2H3 cells: further evidence that TCS disrupts
      mast cell signaling. Our data indicate that TCS is a mitochondrial uncoupler, and
      TCS may affect numerous cell types and functions via this mechanism. Copyright
      (c) 2015 John Wiley & Sons, Ltd.

PMID- 26204823
TI  - Deletion of SPRY4 is a frequent event in secondary acute myeloid leukemia.

PMID- 26204824
TI  - Prognostic factors for survival of patients with newly diagnosed chronic GVHD
      according to NIH criteria.
AB  - Chronic graft versus host disease (cGvHD) is the most common cause of late
      morbidity and mortality after allogeneic hematopoietic stem cell transplantation
      (HSCT). We retrospectively evaluated the impact of NIH classification on outcome
      of patients at our center. Primary endpoint was overall survival at 5 years. Two
      hundred one patients with cGVHD according to NIH were included. Platelets
      <100,000/MUl on day of diagnosis of cGvHD (HR 2.97, 95 % CI 1.7-5.3, p < 0.001),
      female donor (HR 1.78, 95 % CI 1.0-3.2, p = 0.05), and reduced intensity
      conditioning (HR 1.95, 95 % CI 1.0-3.8, p = 0.05) impacted overall survival. Non
      relapse mortality (NRM) was higher for patients with low vs. high platelets: 26 %
      (95 % CI 14-40) vs. 6 % (95 % CI 2-10), p < 0.001, and tended to be higher for
      female vs. male donor: 14 % (95 % CI 7-23) vs. 7 % (95 % CI 3-13), p = 0.08.
      Relapse tended to be higher for recipients of reduced intensity conditioning
      (RIC) vs. myeloablative conditioning (MAC): 33 % (95 % CI 23-43) vs. 20 % (95 %
      CI 10-31), p = 0.06. After excluding patients with myeloma and lymphoma, IgG
      serum levels at diagnosis of cGvHD of 122 patients were correlated with survival.
      IgG levels above normal were associated with worse 2-year overall survival (OS),
      p = 0.04, compared to normal or low IgG levels. Platelet count at diagnosis
      remains the most valid prognostic factor for survival of patients with cGvHD even
      in the era of NIH grading. High IgG level at diagnosis of cGVHD represents a
      potential negative prognostic parameter that deserves further investigation. 

PMID- 26204826
TI  - Surgical treatment after a failed trapeziectomy: A case report.
AB  - Several treatment options exist to surgically treat end-stage trapeziometacarpal
      osteoarthritis. Trapeziectomy is recognized as leading to a mostly acceptable
      functional outcome. Although rarely encountered, persisting failure of the
      trapeziectomy is difficult to address. We present a case where several procedures
      were subsequently performed to treat a failed trapeziectomy condition. First, a
      trapeziometacarpal prosthesis (Arpe((r)), Biomet((r))) was inserted with the two
      components reversed: the cup in the first metacarpal and the stem in the
      scaphoid. This prevented normal mobility and resulted in a non-functional,
      chronically painful joint. Revision arthroplasty was performed with a dual
      mobility component (Ebony((r)), Stryker((r))), replacing the trapezium to
      articulate with the first metacarpal and the scaphoid. This restored the first
      column's length but led to prosthesis instability only 4 months after
      implantation. Finally, first column arthrodesis with iliac bone graft interposed
      between the first metacarpal and scaphoid achieved an acceptable outcome.

PMID- 26204825
TI  - Epidemiology and clinical outcome of lower respiratory tract infections by
      respiratory syncytial virus or parainfluenza virus type 3 in adults receiving
      treatment for either acute leukemia or severe aplastic anemia: a retrospective
      single center study.

PMID- 26204827
TI  - Avulsion of flexor digitorum profundus secondary to enchondroma of the distal
      phalanx. Case report and literature review.
AB  - We report an unusual case of avulsion of the flexor digitorum profundus tendon of
      the ring finger at its insertion, in combination with a pathological fracture of
      the distal phalanx due to enchondroma. The bone lesion was curetted and grafted
      using autogenous bone. The FDP tendon was reattached to the distal phalanx using
      the pullout technique. We describe this case in detail and discuss the surgical
      management through a review of literature. 

PMID- 26204829
TI  - Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond.
AB  - Alemtuzumab is a humanized monoclonal antibody against CD52 (cluster of
      differentiation 52) and is approved for the therapy of relapsing-remitting
      multiple sclerosis. The application of alemtuzumab leads to a rapid, but long
      lasting depletion predominantly of CD52-bearing B and T cells with reprogramming
      effects on immune cell composition resulting in the restoration of tolerogenic
      networks. Alemtuzumab has proven high efficacy in clinical phase II and III
      trials, where interferon beta-1a was used as active comparator. However,
      alemtuzumab is associated with frequent and considerable risks. Most importantly
      secondary autoimmune disease affects 30%-40% of patients, predominantly impairing
      thyroid function. Extensive monitoring and early intervention allow for an
      appropriate risk management. However, new and reliable biomarkers for individual
      risk stratification and treatment response to improve patient selection and
      therapy guidance are a significant unmet need. Only a deeper understanding of the
      underlying mechanisms of action (MOA) will reveal such markers, maximizing the
      best potential risk-benefit ratio for the individual patient. This review
      provides and analyses the current knowledge on the MOA of alemtuzumab. Most
      recent data on efficacy and safety of alemtuzumab are presented and future
      research opportunities are discussed. 

PMID- 26204830
TI  - Inhibition of Mammalian Target of Rapamycin Complex 1 (mTORC1) Downregulates
      ELOVL1 Gene Expression and Fatty Acid Synthesis in Goat Fetal Fibroblasts.
AB  - Elongation of very-long-chain fatty acids 1 (ELOVL1) is a ubiquitously expressed
      gene that belongs to the ELOVL family and regulates the synthesis of very-long
      chain fatty acids (VLCFAs) and sphingolipids, from yeast to mammals. Mammalian
      target of rapamycin complex 1 (mTORC1) is a central regulator of cell metabolism
      and is associated with fatty acids synthesis. In this study, we cloned the cDNA
      that encodes Cashmere goat (Capra hircus) ELOVL1 (GenBank Accession number
      KF549985) and investigated its expression in 10 tissues. ELOVL1 cDNA was 840 bp,
      encoding a deduced protein of 279 amino acids, and ELOVL1 mRNA was expressed in a
      wide range of tissues. Inhibition of mTORC1 by rapamycin decreased ELOVL1
      expression and fatty acids synthesis in Cashmere goat fetal fibroblasts. These
      data show that ELOVL1 expression is regulated by mTORC1 and that mTORC1 has
      significant function in fatty acids synthesis in Cashmere goat. 

PMID- 26204831
TI  - Baicalin Protects Mice from Aristolochic Acid I-Induced Kidney Injury by
      Induction of CYP1A through the Aromatic Hydrocarbon Receptor.
AB  - Exposure to aristolochic acid I (AAI) can lead to aristolochic acid nephropathy
      (AAN), Balkan endemic nephropathy (BEN) and urothelial cancer. The induction of
      hepatic CYP1A, especially CYP1A2, was considered to detoxify AAI so as to reduce
      its nephrotoxicity. We previously found that baicalin had the strong ability to
      induce CYP1A2 expression; therefore in this study, we examined the effects of
      baicalin on AAI toxicity, metabolism and disposition, as well as investigated the
      underlying mechanisms. Our toxicological studies showed that baicalin reduced the
      levels of blood urea nitrogen (BUN) and creatinine (CRE) in AAI-treated mice and
      attenuated renal injury induced by AAI. Pharmacokinetic analysis demonstrated
      that baicalin markedly decreased AUC of AAI in plasma and the content of AAI in
      liver and kidney. CYP1A induction assays showed that baicalin exposure
      significantly increased the hepatic expression of CYP1A1/2, which was completely
      abolished by inhibitors of the Aromatic hydrocarbon receptor (AhR), 3',4'
      dimethoxyflavone and resveratrol, in vitro and in vivo, respectively. Moreover,
      the luciferase assays revealed that baicalin significantly increased the
      luciferase activity of the reporter gene incorporated with the Xenobiotic
      response elements recognized by AhR. In summary, baicalin significantly reduced
      the disposition of AAI and ameliorated AAI-induced kidney toxicity through AhR
      dependent CYP1A1/2 induction in the liver. 

PMID- 26204832
TI  - Sinulariolide Suppresses Human Hepatocellular Carcinoma Cell Migration and
      Invasion by Inhibiting Matrix Metalloproteinase-2/-9 through MAPKs and PI3K/Akt
      Signaling Pathways.
AB  - Sinulariolide is an active compound isolated from the cultured soft coral
      Sinularia flexibilis. In this study, we investigate the migration and invasion
      effects of sinulariolide in hepatocellular carcinoma cell HA22T. Sinulariolide
      inhibited the migration and invasion effects of hepatocellular carcinoma cells in
      a concentration-dependent manner. The results of zymography assay showed that
      sinulariolide suppressed the activities of matrix metalloproteinase (MMP)-2 and
      MMP-9. Moreover, protein levels of MMP-2, MMP-9, and urokinase-type plasminogen
      activator (uPA) were reduced by sinulariolide in a concentration-dependent
      manner. Sinulariolide also exerted an inhibitory effect on phosphorylation of c
      Jun N-terminal kinase (JNK), extracellular signal-regulated kinases (ERK),
      phosphatidylinositol 3-kinase (PI3K), Akt, Focal adhesion kinase (FAK), growth
      factor receptor-bound protein 2 (GRB2). Taken together, these results
      demonstrated that sinulariolide could inhibit hepatocellular carcinoma cell
      migration and invasion and alter HA22T cell metastasis by reduction of MMP-2, MMP
      9, and uPA expression through the suppression of MAPKs, PI3K/Akt, and the
      FAK/GRB2 signaling pathway. These findings suggest that sinulariolide merits
      further evaluation as a chemotherapeutic agent for human hepatocellular
      carcinoma. 

PMID- 26204833
TI  - Association between the NF-E2 Related Factor 2 Gene Polymorphism and Oxidative
      Stress, Anti-Oxidative Status, and Newly-Diagnosed Type 2 Diabetes Mellitus in a
      Chinese Population.
AB  - Oxidative stress is a major risk factor in the onset and progression of type 2
      diabetes mellitus (T2DM). NF-E2 related factor 2 (NRF2) is a pivotal
      transcription factor in oxidative stress related illnesses. This study included
      2174 subjects with 879 cases of newly-diagnosed T2DM and 1295 healthy controls.
      Compared to individuals with the CC genotype, those with the AA genotype had
      lower total anti-oxidative capacity, superoxide dismutase, catalase, glutathione,
      glutathione peroxidase activity; and lower homeostasis model assessment of beta
      cell function index. Those with the AA genotype also had a higher malondialdehyde
      concentration and homeostasis model assessment of insulin resistance index
      values. The frequency of allele A was significantly higher in T2DM subjects
      (29.4%), compared to control subjects (26.1%; p = 0.019). Individuals with the AA
      genotype had a significantly higher risk of developing T2DM (OR 1.56; 95% CI
      1.11, 2.20; p = 0.011), relative to those with the CC genotype, even after
      adjusting for known T2DM risk factors. Our results suggest that the NRF2
      rs6721961 polymorphism was significantly associated with oxidative stress, anti
      oxidative status, and risk of newly-diagnosed T2DM. This polymorphism may also
      contribute to impaired insulin secretory capacity and increased insulin
      resistance in a Chinese population. 

PMID- 26204834
TI  - What Do We Know about the Role of miRNAs in Pediatric Sarcoma?
AB  - Non-coding RNAs have received a lot of attention in recent years, with especial
      focus on microRNAs (miRNAs), so much so that in the just over two decades since
      the first miRNA, Lin4, was described, almost 40,000 publications about miRNAs
      have been generated. Less than 500 of these focus on sarcoma, and only a fraction
      of those on sarcomas of childhood specifically, with some of these representing
      observational studies and others containing functionally validated data. This is
      a group of cancers for which prognosis is often poor and therapeutic options
      limited, and it is especially in these areas that strides in understanding the
      role of non-coding RNAs and miRNAs in particular are to be welcomed. This review
      deals with the main forms of pediatric sarcoma, exploring what is known about the
      diagnostic and prognostic profiles of miRNAs in these tumours and where novel
      therapeutic options might present themselves for further exploration. 

PMID- 26204835
TI  - 14-3-3gamma Regulates Lipopolysaccharide-Induced Inflammatory Responses and
      Lactation in Dairy Cow Mammary Epithelial Cells by Inhibiting NF-kappaB and MAPKs
      and Up-Regulating mTOR Signaling.
AB  - As a protective factor for lipopolysaccharide (LPS)-induced injury, 14-3-3gamma
      has been the subject of recent research. Nevertheless, whether 14-3-3gamma can
      regulate lactation in dairy cow mammary epithelial cells (DCMECs) induced by LPS
      remains unknown. Here, the anti-inflammatory effect and lactation regulating
      ability of 14-3-3gamma in LPS-induced DCMECs are investigated for the first time,
      and the molecular mechanisms responsible for their effects are explored. The
      results of qRT-PCR showed that 14-3-3gamma overexpression significantly inhibited
      the mRNA expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL
      6), interleukin-1beta (IL-1beta) and inducible nitric oxide synthase (iNOS).
      Enzyme-linked immunosorbent assay (ELISA) analysis revealed that 14-3-3gamma
      overexpression also suppressed the production of TNF-alpha and IL-6 in cell
      culture supernatants. Meanwhile, CASY-TT Analyser System showed that 14-3-3gamma
      overexpression clearly increased the viability and proliferation of cells. The
      results of kit methods and western blot analysis showed that 14-3-3gamma
      overexpression promoted the secretion of triglycerides and lactose and the
      synthesis of beta-casein. Furthermore, the expression of genes relevant to
      nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPKs)
      and lactation-associated proteins were assessed by western blot, and the results
      suggested that 14-3-3gamma overexpression inactivated the NF-kappaB and MAPK
      signaling pathways by down-regulating extracellular signal regulated protein
      kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK) and inhibitor of NF
      kappaB (IkappaB) phosphorylation levels, as well as by inhibiting NF-kappaB
      translocation. Meanwhile, 14-3-3gamma overexpression enhanced the expression
      levels of beta-casein, mammalian target of rapamycin (mTOR), ribosomal protein S6
      kinase 1 (S6K1), serine/threonine protein kinase Akt 1 (AKT1), sterol regulatory
      element binding protein 1 (SREBP1) and peroxisome proliferator-activated receptor
      gamma (PPARgamma). These results suggest that 14-3-3gamma was able to attenuate
      the LPS-induced inflammatory responses and promote proliferation and lactation in
      LPS-induced DCMECs by inhibiting the activation of the NF-kappaB and MAPK
      signaling pathways and up-regulating mTOR signaling pathways to protect against
      LPS-induced injury. 

PMID- 26204836
TI  - Genetically Encoded FRET-Sensor Based on Terbium Chelate and Red Fluorescent
      Protein for Detection of Caspase-3 Activity.
AB  - This article describes the genetically encoded caspase-3 FRET-sensor based on the
      terbium-binding peptide, cleavable linker with caspase-3 recognition site, and
      red fluorescent protein TagRFP. The engineered construction performs two
      induction-resonance energy transfer processes: from tryptophan of the terbium
      binding peptide to Tb(3+) and from sensitized Tb(3+) to acceptor--the chromophore
      of TagRFP. Long-lived terbium-sensitized emission (microseconds), pulse
      excitation source, and time-resolved detection were utilized to eliminate
      directly excited TagRFP fluorescence and background cellular autofluorescence,
      which lasts a fraction of nanosecond, and thus to improve sensitivity of
      analyses. Furthermore the technique facilitates selective detection of
      fluorescence, induced by uncleaved acceptor emission. For the first time it was
      shown that fluorescence resonance energy transfer between sensitized terbium and
      TagRFP in the engineered construction can be studied via detection of microsecond
      TagRFP fluorescence intensities. The lifetime and distance distribution between
      donor and acceptor were calculated using molecular dynamics simulation. Using
      this data, quantum yield of terbium ions with binding peptide was estimated.

PMID- 26204837
TI  - Fluoxetine Decreases the Proliferation and Adipogenic Differentiation of Human
      Adipose-Derived Stem Cells.
AB  - Fluoxetine was originally developed as an antidepressant, but it has also been
      used to treat obesity. Although the anti-appetite effect of fluoxetine is well
      documented, its potential effects on human adipose-derived stem cells (ASCs) or
      mature adipocytes have not been investigated. Therefore, we investigated the
      mechanisms underlying the inhibitory effects of fluoxetine on the proliferation
      of ASCs. We also investigated its inhibitory effect on adipogenic
      differentiation. Fluoxetine significantly decreased ASC proliferation, and signal
      transduction PCR array analysis showed that it increased expression of autophagy
      related genes. In addition, fluoxetine up-regulated SQSTM1 and LC3B protein
      expression as detected by western blotting and immunofluorescence. The autophagy
      inhibitor, 3-methyladenine (3-MA), significantly attenuated fluoxetine-mediated
      effects on ASC proliferation and SQSTM1/LC3B expression. In addition, 3-MA
      decreased the mRNA expression of two autophagy-related genes, beclin-1 and Atg7,
      in ASCs. Fluoxetine also significantly inhibited lipid accumulation and down
      regulated the levels of PPAR-gamma and C/EBP-alpha in ASCs. Collectively, these
      results indicate that fluoxetine decreases ASC proliferation and adipogenic
      differentiation. This is the first in vitro evidence that fluoxetine can reduce
      fat accumulation by inhibiting ASC proliferation and differentiation. 

PMID- 26204838
TI  - Structural Variation (SV) Markers in the Basidiomycete Volvariella volvacea and
      Their Application in the Construction of a Genetic Map.
AB  - Molecular markers and genetic maps are useful tools in genetic studies. Novel
      molecular markers and their applications have been developed in recent years.
      With the recent advancements in sequencing technology, the genomic sequences of
      an increasingly great number of fungi have become available. A novel type of
      molecular marker was developed to construct the first reported linkage map of the
      edible and economically important basidiomycete Volvariella volvacea by using 104
      structural variation (SV) markers that are based on the genomic sequences.
      Because of the special and simple life cycle in basidiomycete, SV markers can be
      effectively developed by genomic comparison and tested in single spore isolates
      (SSIs). This stable, convenient and rapidly developed marker may assist in the
      construction of genetic maps and facilitate genomic research for other species of
      fungi. 

PMID- 26204839
TI  - Effects of Plant Growth Hormones on Mucor indicus Growth and Chitosan and Ethanol
      Production.
AB  - The objective of this study was to investigate the effects of indole-3-acetic
      acid (IAA) and kinetin (KIN) on Mucor indicus growth, cell wall composition, and
      ethanol production. A semi-synthetic medium, supplemented with 0-5 mg/L hormones,
      was used for the cultivations (at 32  degrees C for 48 h). By addition of 1 mg/L
      of each hormone, the biomass and ethanol yields were increased and decreased,
      respectively. At higher levels, however, an inverse trend was observed. The
      glucosamine fraction of the cell wall, as a representative for chitosan, followed
      similar but sharper changes, compared to the biomass. The highest level was 221%
      higher than that obtained without hormones. The sum of glucosamine and N-acetyl
      glucosamine (chitin and chitosan) was noticeably enhanced in the presence of the
      hormones. Increase of chitosan was accompanied by a decrease in the phosphate
      content, with the lowest phosphate (0.01 g/g cell wall) being obtained when the
      chitosan was at the maximum (0.45 g/g cell wall). In conclusion, IAA and KIN
      significantly enhanced the M. indicus growth and chitosan production, while at
      the same time decreasing the ethanol yield to some extent. This study shows that
      plant growth hormones have a high potential for the improvement of fungal
      chitosan production by M. indicus. 

PMID- 26204840
TI  - Characterization of a Functional Role of the Bradyrhizobium japonicum Isocitrate
      Lyase in Desiccation Tolerance.
AB  - Bradyrhizobium japonicum is a nitrogen-fixing symbiont of soybean. In previous
      studies, transcriptomic profiling of B. japonicum USDA110, grown under various
      environmental conditions, revealed the highly induced gene aceA, encoding
      isocitrate lyase (ICL). The ICL catalyzes the conversion of isocitrate to
      succinate and glyoxylate in the glyoxylate bypass of the TCA cycle. Here, we
      evaluated the functional role of B. japonicum ICL under desiccation-induced
      stress conditions. We purified AceA (molecular mass = 65 kDa) from B. japonicum
      USDA110, using a His-tag and Ni-NTA column approach, and confirmed its ICL enzyme
      activity. The aceA mutant showed higher sensitivity to desiccation stress (27%
      relative humidity (RH)), compared to the wild type. ICL activity of the wild type
      strain increased approximately 2.5-fold upon exposure to 27% RH for 24 h. The
      aceA mutant also showed an increased susceptibility to salt stress. Gene
      expression analysis of aceA using qRT-PCR revealed a 148-fold induction by
      desiccation, while other genes involved in the glyoxylate pathway were not
      differentially expressed in this condition. Transcriptome analyses revealed that
      stress-related genes, such as chaperones, were upregulated in the wild-type under
      desiccating conditions, even though fold induction was not dramatic (ca. 1.5-2.5
      fold). 

PMID- 26204841
TI  - An Activity-Based Probe for Studying Crosslinking in Live Bacteria.
AB  - Penicillin-binding proteins (PBPs) catalyze the crosslinking of peptidoglycan
      (PG), an essential process for bacterial growth and survival, and a common
      antibiotic target. Yet, despite its importance, little is known about the
      spatiotemporal aspects of crosslinking-largely because of a lack of experimental
      tools for studying the reaction in live bacteria. Here we introduce such a tool:
      an activity-based probe that enables visualization and relative quantitation of
      crosslinking in vivo. In Staphylococcus aureus, we show that fluorescent mimics
      of the natural substrate of PBPs (PG stem peptide) are covalently incorporated
      into the cell wall, installing fluorophores in place of natural crosslinks. These
      fluorescent stem peptide mimics (FSPMs) are selectively recognized by a single
      PBP in S. aureus: PBP4. Thus, we were able to use FSPM pulse-labeling to localize
      PBP4 activity in live cells, showing that it is recruited to the septum in a
      manner dependent on wall teichoic acid.

PMID- 26204842
TI  - [Locum tenens physician--consultant--private physician--attending physician-
      cooperating physician: Clarity in the terminology jungle].

PMID- 26204843
TI  - [Benefit assessments for medical technology devices: Strategic challenges for
      clinical research].

PMID- 26204844
TI  - Effects of strontium ranelate on bone mass and bone turnover in women with
      thalassemia major-related osteoporosis.
AB  - Subjects affected by thalassemia major (TM) often have reduced bone mass and
      increased fracture risk. Strontium ranelate (SrR) is an effective treatment for
      postmenopausal and male osteoporosis. To date, no data exist on the use of SrR in
      the treatment of TM-related osteoporosis. Our aim was to evaluate the effects of
      SrR on bone mineral density (BMD), bone turnover markers and inhibitors of Wnt
      signaling (sclerostin and DKK-1). Twenty-four TM osteoporotic women were
      randomized to receive daily SrR 2 g or placebo in addition to calcium carbonate
      (1,000 mg) and vitamin D (800 IU). BMD at the lumbar spine and femoral neck, bone
      turnover markers (C-terminal telopeptide of procollagen type I [CTX], bone
      specific alkaline phosphatase [BSAP]) and insulin-like growth factor-1 (IGF-1),
      sclerostin and DKK-1 were assessed at baseline and after 24 months. Back pain was
      measured by visual analog scale (VAS) every 6 months. After 24 months, TM women
      treated with SrR had increased their spine BMD values in comparison to baseline
      (p < 0.05). Moreover, they also exhibited a reduction of CTX and sclerostin
      levels (but not DKK-1) and exhibited an increase of BSAP and IGF-1 (p < 0.05);
      however, no significant changes were observed in the placebo group. In the SrR
      group, a reduction of back pain was observed after 18 months in comparison to
      baseline (p < 0.05) and after 24 months in comparison to placebo (p < 0.05). Our
      study reports for the first time the effects of SrR in the treatment of TM
      related osteoporosis. SrR treatment improved BMD and normalized bone turnover
      markers, as well as lowering sclerostin serum levels. 

PMID- 26204845
TI  - Tensile force on human macrophage cells promotes osteoclastogenesis through
      receptor activator of nuclear factor kappaB ligand induction.
AB  - Little is known about the effects of tensile forces on osteoclastogenesis by
      human monocytes in the absence of mechanosensitive cells, including osteoblasts
      and fibroblasts. In this study we consider the effects of tensile force on
      osteoclastogenesis in human monocytes. The cells were treated with receptor
      activator of nuclear factor kappaB ligand (RANKL) to promote osteoclastogenesis.
      Then,expression and secretion of cathepsin K were examined. RANKL and the
      formation of osteoclasts during the osteoclast differentiation process under
      continual tensile stress were evaluated by Western blot. It was also found that 
      100 kPa or lower induces RANKL-enhanced tartrate-resistant acid phosphatase
      activity in a dose-dependent manner. Furthermore, an increased tensile force
      raises the expression and secretion of cathepsin K elevated by RANKL, and is
      concurrent with the increase of TNF-receptor-associated factor 6 induction and
      nuclear factor kappaB activation. Overall, the current report demonstrates that
      tensile force reinforces RANKL-induced osteoclastogenesis by retarding osteoclast
      differentiation. The tensile force is able to modify every cell through dose
      dependent in vitro RANKL-mediated osteoclastogenesis, affecting the fusion of
      preosteoclasts and function of osteoclasts. However, tensile force increased TNF
      receptor-associated factor 6 expression. These results are in vitro findings and
      were obtained under a condition of tensile force. The current results help us to
      better understand the cellular roles of human macrophage populations in
      osteoclastogenesis as well as in alveolar bone remodeling when there is tensile
      stress. 

PMID- 26204846
TI  - Bone mineral density and changes in bone metabolism in patients with obstructive
      sleep apnea syndrome.
AB  - The aim of this study was to evaluate the differences between patients with
      obstructive sleep apnea syndrome (OSAS) and phenotypically similar subjects
      without OSAS in terms of bone mineral density (BMD) and bone turnover markers.
      The study was conducted on 30 males diagnosed with OSAS and 20 healthy males. All
      subjects underwent polysomnographic testing. Calcium, phosphorus parathyroid
      hormone, thyroid stimulating hormone, bone-specific alkaline phosphatase, 25
      hydroxyvitamin D3, osteocalcin, and beta-CrossLaps (beta-CTx) were measured. BMD
      in the lumbar spine (L1-L4) and femoral neck was measured by dual energy X-ray
      absorptiometry. There was no statistically significant difference between the two
      groups in terms of demographic data with the exception of bone mass index and
      waist circumference. (p < 0.05). Analyses showed significantly lower BMD
      measurements in the femoral neck and T-scores in the femoral neck in patients
      diagnosed with OSAS. Serum beta-CTx levels were found to be statistically
      significantly higher in the OSAS group (p = 0.017). In multivariate assessments
      performed for apnea/hypopnea index values, mean saturation O2 levels were found
      to be significantly associated with osteocalcin levels and neck BMD. OSAS
      patients might represent a risk group with respect to loss of BMD and bone
      resorption. It is important to evaluate bone loss in these patients. Further
      studies should be carried out on larger study populations to evaluate the effects
      of chronic hypoxia on BMD in detail. 

PMID- 26204848
TI  - Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on
      Osteoclastic Resorption.
AB  - Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as
      people age. Previous studies have shown controversial results regarding the role
      of in situ AGEs accumulation in osteoclastic resorption. To address this issue,
      this study cultured human osteoclast cells directly on human cadaveric bone
      slices from different age groups (young and elderly) to warrant its relevance to
      in vivo conditions. The cell culture was terminated on the 3rd, 7th, and 10th
      day, respectively, to assess temporal changes in the number of differentiated
      osteoclasts, the number and size of osteoclastic resorption pits, the amount of
      bone resorbed, as well as the amount of matrix AGEs released in the medium by
      resorption. In addition, the in situ concentration of matrix AGEs at each
      resorption pit was also estimated based on its AGEs autofluorescent intensity.
      The results indicated that (1) osteoclastic resorption activities were
      significantly correlated with the donor age, showing larger but shallower
      resorption pits on the elderly bone substrates than on the younger ones; (2)
      osteoclast resorption activities were not significantly dependent on the in situ
      AGEs concentration in bone matrix, and (3) a correlation was observed between
      osteoclast activities and the concentration of AGEs released by the resorption.
      These results suggest that osteoclasts tend to migrate away from initial
      anchoring sites on elderly bone substrate during resorption compared to younger
      bone substrates. However, such behavior is not directly related to the in situ
      concentration of AGEs in bone matrix at the resorption sites. 

PMID- 26204849
TI  - Syngas production by high temperature steam/CO2 coelectrolysis using solid oxide
      electrolysis cells.
AB  - High temperature (HT) steam/CO2 coelectrolysis with solid oxide electrolysis
      cells (SOECs) using the electricity and heat generated from clean energies is an
      important alternative for syngas production without fossil fuel consumption and
      greenhouse gas emissions. Herein, reaction characteristics and the outlet syngas
      composition of HT steam/CO2 coelectrolysis under different operating conditions,
      including distinct inlet gas compositions and electrolysis current densities, are
      systematically studied at 800  degrees C using commercially available SOECs. The
      HT coelectrolysis process, which has comparable performance to HT steam
      electrolysis, is more active than the HT CO2 electrolysis process, indicating the
      important contribution of the reverse water-gas shift reaction in the formation
      of CO. The outlet syngas composition from HT steam/CO2 coelectrolysis is very
      sensitive to the operating conditions, indicating the feasibility of controlling
      the syngas composition by varying these conditions. Maximum steam and CO2
      utilizations of 77% and 76% are achieved at 1.0 A cm(-2) with an inlet gas
      composition of 20% H2/40% steam/40% CO2. 

PMID- 26204847
TI  - Role of osteoclasts in heterotopic ossification enhanced by fibrodysplasia
      ossificans progressiva-related activin-like kinase 2 mutation in mice.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a disorder of skeletal
      malformations and progressive heterotopic ossification. The constitutively
      activating mutation (R206H) of the bone morphogenetic protein type 1 receptor,
      activin-like kinase 2 (ALK2), is responsible for the pathogenesis of FOP.
      Although transfection of the causal mutation of FOP into myoblasts enhances
      osteoclast formation by transforming growth factor-beta (TGF-beta), the role of
      osteoclasts in heterotopic ossification is unknown. We therefore examined the
      effects of alendronate, SB431542 and SB203580 on heterotopic ossification induced
      by the causal mutation of FOP. Total bone mineral content as well as numbers of
      tartrate-resistant acid phosphatase (TRAP)-positive multinucleated and alkaline
      phosphatase (ALP)-positive cells in heterotopic bone were significantly higher in
      muscle tissues implanted with ALK2 (R206H)-transfected mouse myoblastic C2C12
      cells than in the tissues implanted with empty vector-transfected cells in nude
      mice. Alendronate, an aminobisphosphonate, did not affect total mineral content
      or numbers of TRAP-positive multinucleated and ALP-positive cells in heterotopic
      bone, which were enhanced by the implantation of ALK2 (R206H)-transfected C2C12
      cells, although it significantly decreased serum levels of cross-linked C
      telopeptide of type I collagen, a bone resorption index. Moreover, neither
      SB431542, an inhibitor of TGF-beta receptor type I kinase, nor SB203580, an
      inhibitor of p38 mitogen-activated protein kinase, affected the increase in
      heterotopic ossification due to the implantation of ALK2 (R206H)-transfected
      C2C12 cells. In conclusion, the present study indicates that osteoclast
      inhibition does not affect heterotopic ossification enhanced by FOP-related
      mutation. 

PMID- 26204850
TI  - Reduced Graphene Oxide Bipolar Membranes for Integrated Solar Water Splitting in
      Optimal pH.
AB  - The integration of light absorbers and catalysts for the water splitting process
      requires a membrane capable of both ion and electron management and product
      separation to realize efficient solar fuels systems. Bipolar membranes can
      maintain a pH gradient for optimal reaction conditions by the dissociation of
      water. Such membranes that contain graphene in the interfacial layer are
      fabricated by the chemical reduction of a uniformly deposited graphene oxide
      layer to convert sp(3) catalyst regions to sp(2) conductive regions. The
      resulting electrical and water dissociation properties are optimized by adjusting
      the exposure conditions, and treatments of less than 5 min render an interface
      that exceeds the conductivity requirements for integrated solar water splitting
      and increases the overpotential by <0.3 V. Integration with photoelectrodes is
      examined by characterizing the electrical interface formed between graphene and
      Si microwires, and we found that efficient Ohmic junctions are possible.

PMID- 26204851
TI  - Heterostructure of Au nanocluster tipping on a ZnS quantum rod: controlled
      synthesis and novel luminescence.
AB  - Heterostructures of metal nanoparticles and semiconductors are widely studied for
      their unique properties. However, few reports are available on the
      heterostructure of metal nanoclusters and semiconductors. In the present study, a
      heterostructure, in which gold nanoclusters selectively locate at ZnS quantum rod
      (QR) tips, was fabricated using a two-step solvothermal route. The composition,
      intrinsic crystallography, and junction of the prepared heterostructure were
      thoroughly investigated, and it was observed to exhibit novel luminescent
      behaviours. By comparison with the individual components of ZnS QRs and gold
      clusters, the resultant heterostructure shows an enhanced exciton emission and
      complete depression of defect emission for the ZnS component, and a pronounced
      red emission for the gold nanocluster component. The mechanism of these
      properties and the charge transfer between gold nanoclusters and ZnS QRs were
      also explored. The size and location of gold in the heterostructure were also
      controlled during synthesis to study their effects on the luminescence. 

PMID- 26204856
TI  - Assessing the sustainability and adaptive capacity of the gooseneck barnacle co
      management system in Asturias, N. Spain.
AB  - The gooseneck barnacle fishery in Asturias (N. Spain) has undergone three
      important changes: (1) the early implementation of a co-management system based
      on Territorial User Rights for Fishing, (2) a change in management measures (due
      to a decrease in landings), and (3) an economic crisis. This has allowed us to
      analyze the systems' sustainability in time through examining five critical
      variables: landings, effort, catch per unit effort (CPUE), mean market prices,
      and annual revenue. Additionally, we used focus groups and questionnaires to
      determine the response of the system to these three changes. Co-management has
      succeeded in maintaining or increasing CPUE throughout all management areas and
      produced stable mean market prices. This was achieved through flexible management
      policies and adaptive strategies adopted by the fishers, such as increased
      selectivity and diversification. The analysis of this fishery provides important
      lessons regarding the need to understand the evolutionary dynamics of co
      management and the importance of embracing adaptive capacity. 

PMID- 26204861
TI  - Whole-genome sequencing can improve care of severely ill infants: study finds
      technique yields high rate of diagnoses, aids decision making related to
      treatment.

PMID- 26204862
TI  - Can adolescents make predictive genetic testing decisions?: study suggests
      children age 12 and older may be competent to give consent.

PMID- 26204857
TI  - Does age influence the success of intra-tympanic steroid treatment in idiopathic
      sudden deafness?
AB  - CONCLUSIONS: The present study shows that AGE, DELAY, and PTA_PRE may be
      considered factors influencing therapeutic success in intra-tympanic steroid
      therapy. OBJECTIVE: The aim of the study is to evaluate the relationship between
      the therapeutic success of intra-tympanic prednisolone therapy and age, in
      patients affected by idiopathic sudden sensorineural hearing loss (ISSNHL),
      considering the influence of factors such as delay, gender, and pure tone average
      (PTA) pre-therapy. METHOD: This retrospective study involved 402 consecutive
      patients, affected by unilateral ISSNHL between January 2009 and January 2014.
      Patients were divided into two groups based on age: group one with 94 patients
      aged over 65 years and group two with all 402 patients enrolled in the study,
      including those over 65. RESULTS: PTA recorded before the beginning of the
      therapy (PTA_PRE) in group one was worse than for group two. In both groups the
      therapy was significantly effective in improving hearing thresholds, even if
      PTA_PRE was significant and negatively correlated with success rate. This effect
      disappeared within the population over 65. On average, each day of DELAY from the
      onset of hearing loss to the beginning of therapy cuts almost 2% of the
      possibility to recover. AGE was negative and significant when specified
      continuously for group two.

PMID- 26204863
TI  - Surgery for acute type A aortic dissection.

PMID- 26204864
TI  - Hybrid of a hybrid: A story in evolution.

PMID- 26204865
TI  - In vitro hemodynamic characterization of HeartMate II at 6000 rpm: Implications
      for weaning and recovery.
AB  - OBJECTIVES: Pump-off testing to assess left ventricular recovery is not an option
      for continuous-flow left ventricular assist devices unless measures are taken to
      prevent pump regurgitation. The purpose of this bench study was to characterize
      the hemodynamics and pump flow of the HeartMate II (Thoratec Corp, Pleasanton,
      Calif) left ventricular assist device at 6000 rpm, the speed commonly used
      clinically to determine left ventricular recovery. METHODS: The HeartMate II
      device was operated in a mock loop at 3 speeds (6000, 8000, and 10,000 rpm). We
      acquired pressure-flow curves in each steady state. In pulsatile mode with the
      pneumatic ventricle (heart simulator) activated, pump flow, total flow, and
      aortic pressure data were obtained under conditions simulating normal heart
      function or heart failure. RESULTS: A large regurgitant flow during diastole was
      confirmed in normal heart function at 6000 rpm support; however, the net flow was
      zero, and there were no differences in the mean aortic pressure between 6000 rpm
      support and no left ventricular assist device support. In contrast, in the heart
      failure condition, left ventricular assist device flow at 6000 rpm significantly
      contributed to the mean aortic pressure and total flow because there was less
      regurgitant flow. CONCLUSIONS: The net pump flow generated by the HeartMate II
      device at 6000 rpm depends on the degree of residual left ventricular function.
      In the setting of improved left ventricular function, at 6000 rpm, we noted a
      large regurgitant flow that reloaded the left ventricle. Although this "marker"
      can serve as a useful indicator for left ventricular recovery, assessing left
      ventricular recovery at this speed is flawed unless measures are taken to prevent
      regurgitant flow.

PMID- 26204866
TI  - Mock loop revelations and the calculus for recovery.

PMID- 26204867
TI  - It is still mostly about the mitral valve.

PMID- 26204868
TI  - Can papillary muscle interventions improve mitral valve repair durability for
      ischemic mitral regurgitation?

PMID- 26204869
TI  - We need a better way to repair ischemic mitral regurgitation.

PMID- 26204870
TI  - Orientation of bileaflet mechanical aortic valve prostheses for optimal
      evaluation by transthoracic echocardiography.

PMID- 26204871
TI  - Turning to the truth: Is mechanical aortic valve orientation important in
      transthoracic echocardiographic detection of prosthetic dysfunction and
      paravalvular endocarditis complications?

PMID- 26204872
TI  - Freedom SOLO: Premature failures or technical flaws during implantation?

PMID- 26204873
TI  - On explaining the cause with the effect.

PMID- 26204874
TI  - Total arterial revascularization of triple vessel coronary disease based on
      combined internal thoracic and radial artery grafts.

PMID- 26204875
TI  - Hybrid palliation for hypoplastic left heart syndrome: Navigating the gray zone.

PMID- 26204876
TI  - The case for total arterial revascularisation.

PMID- 26204877
TI  - A range of options for staged palliation of hypoplastic left heart syndrome.

PMID- 26204878
TI  - Do lung secondary nodules always mean metastasis?

PMID- 26204879
TI  - Secondary nodules: Evaluate carefully but do no harm.

PMID- 26204880
TI  - Pulmonary valve replacement: A sutureless, surgical alternative?

PMID- 26204881
TI  - How do physicians perceive quality of life? Ethical questioning in neonatology.
AB  - BACKGROUND: The outcome of very preterm infants is marked by the development of
      complications that can have an impact on the quality of life of the children and
      their families. The concept of quality of life and its evaluation in the long
      term raise semantic and ethical problems for French physicians in perinatal care.
      Our reflection aims to gain a better understanding of the representations
      surrounding quality of life in neonatal medicine. DISCUSSION: If French
      physicians hesitate to face this concept (through self-interest and
      apprehension), it is because the debate has become more complex. Formerly, the
      dilemma was between respect for life versus quality of life. Today, although this
      dilemma is still with us, the questions raised by French physicians show us that
      autonomy is given increasing importance. The equation to be solved now contains
      three variables: respect for life, well-being, autonomy. So we find ourselves
      between three positions and no longer two: respect for life (the ethics of
      conviction), quality of life based on autonomy (rationalist and secular
      deontologism), and quality of life based on the differential between well-being
      and suffering (utilitarianism). A solution could lie in consequentialism, which
      integrates the consequences for future generations in terms of both safeguarding
      of autonomy and quality of life, and puts the sacredness of life in second place
      but without sacrificing it. By evaluating their future quality of life, we can
      better respond to the needs of these children.

PMID- 26204882
TI  - The functions of non-reproductive mounts among male Barbary macaques (Macaca
      sylvanus).
AB  - Same-sex, non-reproductive mounts have been observed in a number of primate
      species and in various social contexts. However, the function of non-reproductive
      mounts is still largely unknown. We aimed to test whether non-reproductive mounts
      function to assert dominance and as appeasement behavior in male Barbary
      macaques. We analyzed post-mount behavior in 54 macaques belonging to two captive
      groups at Trentham Monkey Forest in Staffordshire, using 10 min post
      mount/matched-control focal sessions collected either on the mounter or the
      mountee. In support of the dominance assertion hypothesis, the higher-ranking
      male within a mounting pair was more likely to be the mounter than the mountee,
      and to mock bite the lower-ranking male. In support of the appeasement
      hypothesis, the former mounting partners were more likely to exchange grooming
      and to have a lower frequency of self-scratching (a measure of social tension)
      after a non-reproductive mount than in control sessions. Our study indicates that
      non-reproductive mounts have different and not mutually exclusive functions and
      can modulate the quality of social interactions among group members. We discuss
      the possible factors that can affect the occurrence of non-reproductive mounts
      within and between species.

PMID- 26204883
TI  - Endoscopic ultrasound-guided drainage of an amoebic liver abscess extending into
      the hepatic subcapsular space.
AB  - Here, we report a case of an amoebic liver abscess (ALA) successfully treated
      with endoscopic ultrasound (EUS)-guided liver abscess drainage (EUS-LAD). A 37
      year-old male with a liver abscess was referred to our hospital due to disease
      progression despite receiving antibiotic therapy. Computed tomography showed an
      intrahepatic abscess extending into the hepatic subcapsular space. The abscess
      could not be punctured through the hepatic parenchyma percutaneously due to the
      presence of hepatic subcapsular lesions. Hence, EUS-LAD was performed via the
      transhepatic approach through the stomach. A 5-Fr pigtail-type nasocystic tube
      was inserted into the abscess through the hepatic parenchyma, with no procedure
      related complications. The contents of the abscess had the appearance of anchovy
      paste which made us suspect an amoebic abscess; therefore, we started antibiotic
      therapy with metronidazole. Afterwards, serum anti-amoebic antibodies were found
      to be positive and the diagnosis of ALA was confirmed. Two weeks later, the size
      of the abscess decreased, and the patient's clinical symptoms disappeared. Hence,
      the tube was removed. There were no signs of recurrence during the follow-up
      period. The use of EUS-LAD for pyogenic or tuberculous abscesses has been
      reported previously. EUS-LAD for an ALA, similar to that for other liver
      abscesses, is an effective alternative to percutaneous transhepatic abscess
      drainage or surgical treatment. 

PMID- 26204884
TI  - Natural history and quality of life in patients with cystine urolithiasis: a
      single centre study.
AB  - OBJECTIVE: To describe the natural history and quality of life (QoL) in patients
      with cystine urolithiasis. PATIENTS AND METHODS: A cohort study was carried out
      involving participants recruited from a single surgeon's case mix. Patients with
      cystinuria and related urolithiasis were invited to complete a questionnaire
      involving demographic information, use of medical treatment, surgical
      interventions and the 36-item short-form 36-item short-form health survey (SF
      36). RESULTS: In all, 14 patients completed the survey. The SF-36 survey showed
      lower QoL than the general public in seven of eight domains. The mean
      interventional rate in patients with cystinuria was 10.6 procedures per patient.
      Most patients reported previous use of d-penicillamine and urinary alkalinisation
      medications, with most ceasing due to side-effects or lack of perceived efficacy.
      CONCLUSION: Cystinuria is associated with a high rate of surgical intervention
      and lower QoL than the general public. Individuals with this condition report
      that medical management is either ineffective or poorly tolerated. There is a
      need for further improvements in medical management of cystinuria, to reduce the
      rate of operative intervention.

PMID- 26204885
TI  - Association of sarcopenia and observed physical performance with attainment of
      multidisciplinary team planned treatment in non-small cell lung cancer: an
      observational study protocol.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) frequently presents in advanced
      stages. A significant proportion of those with reportedly good ECOG performance
      status (PS) fail to receive planned multidisciplinary team (MDT) treatment, often
      for functional reasons, but an objective decline in physical performance is not
      well described. Sarcopenia, or loss of muscle mass, is an integral part of cancer
      cachexia. However, changes in both muscle mass and physical performance may
      predate clinically overt cachexia, and may be present even with normal body mass
      index. Physical fitness for treatment is currently subjectively assessed by means
      of the PS score, which may be inadequate in predicting tolerance to treatment.
      This study aims to evaluate whether measuring physical performance and muscle
      mass at baseline in NSCLC patients, in addition to PS score, is able to predict
      commencement and successful completion of MDT-planned treatment. METHODS/DESIGN:
      This is a prospective, single-centre exploratory study of NSCLC patients
      attending a Rapid Access Lung Cancer clinic. Baseline data collected are (methods
      in brackets): physical performance (Short Physical Performance Battery), muscle
      mass (bioelectrical impedance +/- dual energy x-ray absorptiometry), patient and
      physician-assessed PS (ECOG and Karnofsky), nutritional status and presence of
      cachexia. Longitudinal data consists of receipt and completion of MDT treatment
      plan. The primary outcome measure is commencement of MDT-planned treatment, and
      important secondary outcomes include successful completion of treatment, length
      of stay in surgical patients, and risk of chemotherapy- and radiotherapy-related
      side effects. DISCUSSION: A more comprehensive assessment of phenotype,
      particularly with regards to physical performance and muscle mass, will provide
      additional discriminatory information of patients' fitness for treatment. If
      positive, this study has the potential to identify targets for early intervention
      in those who are at risk of deterioration. This will subsequently enable
      optimisation of performance of patients with NSCLC, in anticipation of systemic
      treatment.

PMID- 26204886
TI  - CDH1 and IL1-beta expression dictates FAK and MAPKK-dependent cross-talk between
      cancer cells and human mesenchymal stem cells.
AB  - INTRODUCTION: Tumor microenvironment conferred by stromal (mesenchymal) stem
      cells (MSCs) plays a key role in tumor development, progression, and response to
      therapy. Defining the role of MSCs in tumorigenesis is crucial for their safe
      utilization in regenerative medicine. Herein, we conducted comprehensive
      investigation of the cross-talk between human MSCs (hMSCs) and 12 cancer cell
      lines derived from breast, prostate, colon, head/neck and skin. METHODS: Human
      bone marrow-derived MSC line expressing green fluorescence protein (GFP) (hMSC
      GFP) were co-cultured with the following cancer cell lines: (MCF7, BT-20, BT-474,
      MDA-MB-468, T-47D, SK-BR-3, MDA-MB-231, PC-3, HT-29, MDA-MB-435s, and FaDu) and
      changes in their morphology were assessed using fluorescent microscopy. For
      cellular tracking, cells were labeled with Vybrant DiO, DiL, and DiD lipophilic
      dyes. Time-lapse microscopy was conducted using Nikon BioStation IM-Q. Stable
      expression of mCherry, and luciferase genes was achieved using lentiviral
      technology. IL1-Beta neutralizing experiments were conducted using soluble
      recombinant IL-1R (srIL-1R). Changes in gene expression in sorted hMSCs were
      assessed using Agilent microarray platform while data normalization and
      bioinformatics were conducted using GeneSpring software. RESULTS: We observed a
      dynamic interaction between cancer cells and hMSCs. High CDH1 (E-cadherin) and
      low IL1-Beta expression by cancer cells promoted reorganization of hMSCs into a
      niche-like formation, which was dependent on direct cell-cell contact. Our data
      also revealed transfer of cellular components between cancer cells and hMSCs as
      one possible mechanism for intercellular communication. Global gene expression
      analysis of sorted hMSCs following co-culturing with MCF7 and BT-20 cells
      revealed enrichment in signaling pathways related to bone formation, FAK and
      MAPKK signaling. Co-culturing hMSCs with MCF7 cells increased their growth
      evidenced by increase in Ki67 and PCNA staining in tumor cells in direct contact
      with hMSCs niche. On the other hand, co-culturing hMSCs with FaDu, HT-29 or MDA
      MB-231 cells led remarkable decline in their cell growth. CONCLUSIONS: Dynamic
      interaction exists between hMSCs and cancer cells. CDH1 and IL1-Beta expression
      by cancer cells mediates the crosstalk between hMSCs and cancer cells. We propose
      a model where hMSCs act as the first line of defense against cancer cell growth
      and spread.

PMID- 26204887
TI  - Better reporting for better research: a checklist for reproducibility.

PMID- 26204888
TI  - Erratum to: The Organizational Account of Function is an Etiological Account of
      Function.

PMID- 26204890
TI  - Synthesis, kinetic mechanism and docking studies of vanillin derivatives as
      inhibitors of mushroom tyrosinase.
AB  - The purpose of the present study was to discover the extent of contribution to
      antityrosinase activity by adding hydroxy substituted benzoic acid, cinnamic acid
      and piperazine residues to vanillin. The study showed the transformation of
      vanillin into esters as shown in (4a-4d), (6a-6b), and (8a-8b). In addition, the
      relationship between structures of these esters and their mushroom tyrosinase
      inhibitory activity was explored. The kinetics of inhibition on mushroom
      tyrosinase by these esters was also investigated. It was found that hydroxyl
      substituted benzoic acid derivatives were weak inhibitors; however hydroxy or
      chloro substituted cinnamic acid and piperazine substituted derivatives were able
      to induce significant tyrosinase inhibition. The mushroom tyrosinase (PDBID 2ZWE)
      was docked with synthesized vanillin derivatives and their calculated binding
      energies were compared with experimental IC50 values which provided positive
      correlation. The most potent derivative 2-(4-formyl-2-methoxyphenoxy)-2-oxoethyl
      (2E)-3-(4-hydroxyphenyl)prop-2-enoate (6a) possesses hydroxy substituted cinnamic
      acid scaffold having IC50 value 16.13 MUM with binding energy of -7.2 kcal/mol.
      The tyrosinase inhibitory activity of (6a) is comparable with standard kojic
      acid. Kinetic analysis indicated that compound 6a was mixed-type tyrosinase
      inhibitor with inhibition constant values Ki (13 MUM) and Ki' (53 MUM) and formed
      reversible enzyme inhibitor complex. The active vanillin analog (6a) was devoid
      of toxic effects as shown in cytotoxic studies.

PMID- 26204889
TI  - Relationship of short-term blood pressure variability with carotid intima-media
      thickness in hypertensive patients.
AB  - BACKGROUND: High blood pressure (BP) is among significant risk factor for stroke
      and other vascular occurrences, it experiences nonstop fluctuations over time as
      a result of a complex interface among cardiovascular control mechanisms. Large
      blood pressure variability (BPV) has been proved to be promising in providing
      potential regulatory mechanisms of the cardiovascular system. Although the
      previous studies also showed that BPV is associated with increased carotid intima
      media thickness (IMT) and plaque, whether the correlation between variability in
      blood pressure and left common carotid artery-intima-media thickness (LCCA-IMT)
      is stronger than right common carotid artery-intima-media thickness (RCCA-IMT)
      remains uncertain in hypertension. METHODS: We conduct a study (78 hypertensive
      subjects, aged 28-79) to evaluate the relationship between BPV and carotid intima
      media thickness in Shenzhen. The blood pressure was collected using the 24 h
      ambulatory blood pressure monitoring, and its variability was evaluated using
      standard deviation (SD), coefficient of variation (CV), and average real
      variability (ARV) during 24 h, daytime and nighttime. All the IMT measurements
      are collected by ultrasound. RESULTS: As the results showed, 24 h systolic blood
      pressure variability (SBPV) evaluated by SD and ARV were significantly related to
      LCCA-IMT (r(1) = 0.261, P = 0.021; r(1) = 0.262, P = 0.021, resp.). For the
      daytime diastolic blood pressure variability (DBPV), ARV indices were
      significantly related to LCCA-IMT (r(1) = 0.239, P = 0.035), which differed form
      BPV evaluated by SD and CV. For the night time, there is no significant
      correlation between the BPV and IMT. Moreover, for all the subjects, there is no
      significant correlation between the BPV and RCCA-IMT/number of plaques, whereas,
      the SD, CV, and ARV of daytime SBP showed a positive correlation with LCCA-IMT
      (r(1) = 0.312, P = 0.005; r(1) = 0.255, P = 0.024; r(1) = 0.284, P = 0.012,
      resp.). Moreover, the ARV of daytime SBPV, 24 h SBPV and nighttime DBPV showed a
      positive correlation with the number of plaques of LCCA (r(1) = 0.356, P = 0.008;
      r(1) = 0.297, P = 0.027; r(1) = 0.278, P = 0.040, resp.). In addition, the number
      of plaques in LCCA had higher correlation with pulse pressure and diastolic blood
      pressure than that in RCCA. And multiple regression analysis indicated LCCA-IMT
      might not only be influenced by age or smoking but also by the SD index of
      daytime SBPV (p = 0.035). CONCLUSIONS: The results show that SBPV during daytime
      and 24 h had significant correlation with IMT, for the hypertensive subjects from
      the southern area of China. Moreover, we also found the daytime SBPV to be the
      best predictor for the progression of IMT in multivariate regression analysis. In
      addition, the present study suggests that the correlation between BPV and left
      common carotid artery-intima-media thickness/number of plaques is stronger than
      right common carotid artery-intima-media thickness/number of plaques.

PMID- 26204891
TI  - Cyclen-based double-tailed lipids for DNA delivery: Synthesis and the effect of
      linking group structures.
AB  - The gene transfection efficiency (TE) of cationic lipids is largely influenced by
      the lipid structure. Six novel 1, 4, 7, 10-tetraazacyclododecane (cyclen)-based
      cationic lipids L1-L6, which contain double oleyl as hydrophobic tails, were
      designed and synthesized. The difference between these lipids is their diverse
      backbone. Liposomes prepared by the lipids and DOPE showed good DNA affinity, and
      full DNA condensation could be achieved at N/P of 4 to form lipoplexes with
      proper size and zeta-potentials for gene transfection. Structure-activity
      relationship of these lipids as non-viral gene delivery vectors was investigated.
      It was found that minor backbone structural variations, including linking group
      and the structural symmetry would affect the TE. The diethylenetriamine derived
      lipid L4 containing amide linking bonds gave the best TE, which was several times
      higher than commercially available transfection reagent lipofectamine 2000.
      Besides, these lipids exhibited low cytotoxicity, suggesting their good
      biocompatibility. Results reveal that such type of cationic lipids might be
      promising non-viral gene vectors, and also afford us clues for the design of
      novel vectors with higher TE and biocompatibility. 

PMID- 26204892
TI  - Evaluation of lipase levels in patients with nephropathia epidemica--no evidence
      for acute pancreatitis.
AB  - BACKGROUND: The most common causative agent for hemorrhagic fever with renal
      syndrome in Germany is Puumala virus (PUUV) and a high percentage of patients
      with PUUV infection have gastrointestinal (GI) symptoms. The aim of the present
      study was to determine the prevalence of increased lipase levels and acute
      pancreatitis during nephropathia epidemica (NE) in 166 patients from Germany.
      METHODS: Clinical and laboratory data during the acute phase of the disease were
      obtained from medical reports and files from 456 patients during acute hantavirus
      infection. Patients in whom serum lipase levels were determined during acute
      course of the disease were included in the study. RESULTS: Lipase levels at the
      time of diagnosis were determined in 166 of the 456 NE patients (36%). Of the 166
      patients, 25 (15%) had elevated lipase levels at the time of admission to
      hospital or first contact with general practitioner/nephrologist. In total 7
      patients had a threefold increased serum lipase above the normal range. Abdominal
      pain was not more often present in the group of patients with elevated serum
      lipase compared to the lipase-negative group (9/25 vs 58/141). Abdominal
      ultrasound and CT scans revealed no signs of pancreatitis in any of the patients.
      Patients with elevated serum lipase had higher serum creatinine peak levels (p =
      0.03) during the course of the disease. CONCLUSIONS: Elevated lipase levels were
      common in our patient cohort and might reflect a more severe form of NE. NE does
      not lead to acute pancreatitis.

PMID- 26204893
TI  - Avian colibacillosis: still many black holes.
AB  - Avian pathogenic Escherichia coli (APEC) strains cause severe respiratory and
      systemic diseases, threatening food security and avian welfare worldwide.
      Intensification of poultry production and the quick expansion of free-range
      production systems will increase the incidence of colibacillosis through greater
      exposure of birds to pathogens and stress. Therapy is mainly based on
      antibiotherapy and current vaccines have poor efficacy. Serotyping remains the
      most frequently used diagnostic method, only allowing the identification of a
      limited number of APEC strains. Several studies have demonstrated that the most
      common virulence factors studied in APEC are all rarely present in the same
      isolate, showing that APEC strains constitute a heterogeneous group. Different
      isolates may harbor different associations of virulence factors, each one able to
      induce colibacillosis. Despite its economical relevance, pathogenesis of
      colibacillosis is poorly understood. Our knowledge on the host response to APEC
      is based on very descriptive studies, mostly restricted to bacteriological and
      histopathological analysis of infected organs such as lungs. Furthermore, only a
      small number of APEC isolates have been used in experimental studies. In the
      present review, we discuss current knowledge on APEC diversity and virulence,
      including host response to infection and the associated inflammatory response
      with a focus on pulmonary colibacillosis. 

PMID- 26204895
TI  - Challenges to malaria surveillance following elimination of indigenous
      transmission: findings from a hospital-based study in rural Sri Lanka.
AB  - INTRODUCTION: Sri Lanka has eliminated local transmission of malaria. Assessing
      physician preparedness for early case detection is important, in order to prevent
      re-establishment of local transmission. METHODS: Adherence to malaria screening
      practices in patients admitted with fever to 12 hospitals in a previously malaria
      endemic district was evaluated using a cross sectional survey. In addition,
      knowledge and attitudes among doctors on current malaria surveillance practices
      and treatment recommendations was assessed. RESULTS: Of 403 fever patients, 150
      warranted screening for malaria under the criteria defined by the Anti Malaria
      Campaign (AMC), with 93 of them having fever for over 7 days. Of these eligible
      patients, 12.6% (19/150) were investigated by doctors (including 3 persons with
      fever over 7 days), 14.6% (22/150) by laboratory staff and 72.6% (109/150) by the
      research team. The majority of doctors were not familiar with the treatment
      guidelines for malaria (76.5%, 75/98). CONCLUSIONS: Mandatory continuous medical
      education programmes need to continue to ensure that malaria remains on the
      differential diagnosis of a fever patient, especially in patients with fever over
      7 days. It is essential to publicize the availability of free-of-charge malaria
      diagnostic facilities, and to ensure that proper notification procedures are
      followed when a malaria patient is diagnosed.

PMID- 26204894
TI  - Lung necrosis and neutrophils reflect common pathways of susceptibility to
      Mycobacterium tuberculosis in genetically diverse, immune-competent mice.
AB  - Pulmonary tuberculosis (TB) is caused by Mycobacterium tuberculosis in
      susceptible humans. Here, we infected Diversity Outbred (DO) mice with ~100
      bacilli by aerosol to model responses in a highly heterogeneous population.
      Following infection, 'supersusceptible', 'susceptible' and 'resistant' phenotypes
      emerged. TB disease (reduced survival, weight loss, high bacterial load)
      correlated strongly with neutrophils, neutrophil chemokines, tumor necrosis
      factor (TNF) and cell death. By contrast, immune cytokines were weak correlates
      of disease. We next applied statistical and machine learning approaches to our
      dataset of cytokines and chemokines from lungs and blood. Six molecules from the
      lung: TNF, CXCL1, CXCL2, CXCL5, interferon-gamma (IFN-gamma), interleukin 12 (IL
      12); and two molecules from blood - IL-2 and TNF - were identified as being
      important by applying both statistical and machine learning methods. Using
      molecular features to generate tree classifiers, CXCL1, CXCL2 and CXCL5
      distinguished four classes (supersusceptible, susceptible, resistant and non
      infected) from each other with approximately 77% accuracy using completely
      independent experimental data. By contrast, models based on other molecules were
      less accurate. Low to no IFN-gamma, IL-12, IL-2 and IL-10 successfully
      discriminated non-infected mice from infected mice but failed to discriminate
      disease status amongst supersusceptible, susceptible and resistant M.
      tuberculosis-infected DO mice. Additional analyses identified CXCL1 as a
      promising peripheral biomarker of disease and of CXCL1 production in the lungs.
      From these results, we conclude that: (1) DO mice respond variably to M.
      tuberculosis infection and will be useful to identify pathways involving necrosis
      and neutrophils; (2) data from DO mice is suited for machine learning methods to
      build, validate and test models with independent data based solely on molecular
      biomarkers; (3) low levels of immunological cytokines best indicate a lack of
      exposure to M. tuberculosis but cannot distinguish infection from disease. 

PMID- 26204896
TI  - Promotion of influenza vaccination among health care workers: findings from a
      tertiary care children's hospital in Italy.
AB  - BACKGROUND: The aims of this study were: a) to evaluate attitudes and practices
      of health care workers (HCWs) towards influenza vaccination and their opinion
      regarding a vaccination promotion toolkit; b) to estimate hospital HCWs'
      influenza vaccination coverage rates (VC). METHODS: The Bambino Gesu Children's
      Hospital (OPBG) is an academic hospital in Italy. Since 2009, free influenza
      vaccination is offered to HCWs during working hours. In October-December 2013, a
      communication campaign based on a standardized toolkit was conducted. In December
      2013, we performed a cross-sectional survey in a sample of hospital wards, based
      on a self-administered questionnaire including participants' characteristics;
      self-reported influenza vaccination history; reasons for vaccination or missed
      vaccination; opinion regarding the toolkit. Multivariable logistic analysis was
      used to assess independent predictors of influenza vaccination status. Annual VC
      for years 2009-2013 was estimated by using the number of seasonal influenza
      vaccine doses administered to HCWs as numerator, and the number of hospital HCWs
      as denominator. RESULTS: Out of 191 HCWs who participated in the survey, 35.6%
      reported at least one influenza vaccination during their life; 6.8% adhered to
      annual revaccination. Years of service and professional category were
      significantly and independently associated with vaccination (adjusted-OR: 2.4 for
      > 10 years of service, compared to < 5 years of service; adjusted-OR: 2.6 for
      physicians compared to nurses). Patient protection was the main reported reason
      for vaccination (34.3%); considering influenza a mild disease was the main reason
      for non-vaccination (36.9%); poor vaccine effectiveness was the main reason for
      missed annual revaccination (28.8%). Overall, 75% of respondents saw at least one
      promotion tool; 65.6% of them found the information useful. Hospital VC decreased
      from 30% in 2009, to 5% in 2012. In 2013, VC was 14%. CONCLUSIONS: Satisfactory
      influenza VC in HCWs is hard to achieve. In 2013, along with the toolkit
      implementation, we observed an increase in HCWs' vaccination coverage,
      nevertheless, it remained unsatisfactory. Tailored information strategies
      targeting nurses and recently employed HCWs should be implemented. Institution of
      declination statements, adding influenza vaccination to financial incentive
      systems, or vaccination requirements should also be considered to increase
      influenza VC among HCWs.

PMID- 26204898
TI  - "Dispersal" of asylum seeking women in UK during pregnancy.

PMID- 26204900
TI  - Exploring Diabetic Foot Exam Performance in a Specialty Clinic.
AB  - Detection of diabetic foot complications is key to amputation prevention. This
      study used survey and retrospective record review to examine the relationship
      between frequency and performance of clinician's diabetic foot examinations on
      performance of patient home self-foot examinations. An additional aim was to
      assess clinician performance of annual foot examination per American Diabetes
      Association (ADA) guidelines in a specialty clinic. The relationships between
      demographic characteristics, diabetic foot ulcer beliefs, health literacy, HbA1c
      level, and foot self-exam performance was also examined. No relationship was
      found between the performance frequency of foot examinations by providers and
      patient self-examination ( N = 88). The presence of specific barriers to self
      management was significantly higher in those patients who did not complete daily
      home self-foot examinations. Only 16% of patients' charts reviewed met the ADA
      criteria for a complete annual foot exam. Motivational interviewing during
      patient visits could be a strategy to break down barriers to self-foot exam
      performance. Furthermore, the development of an Electronic Medical Record (EMR)
      based diabetic foot exam template to improve provider documentation may improve
      compliance with ADA recommendations.

PMID- 26204899
TI  - Paracrine Wnt1 Drives Interstitial Fibrosis without Inflammation by
      Tubulointerstitial Cross-Talk.
AB  - AKI with incomplete epithelial repair is a major contributor to CKD characterized
      by tubulointerstitial fibrosis. Injury-induced epithelial secretion of
      profibrotic factors is hypothesized to underlie this link, but the identity of
      these factors and whether epithelial injury is required remain undefined. We
      previously showed that activation of the canonical Wnt signaling pathway in
      interstitial pericytes cell autonomously drives myofibroblast activation in vivo.
      Here, we show that inhibition of canonical Wnt signaling also substantially
      prevented TGFbeta-dependent myofibroblast activation in vitro. To investigate
      whether Wnt ligand derived from proximal tubule is sufficient for renal
      fibrogenesis, we generated a novel mouse strain with inducible proximal tubule
      Wnt1 secretion. Adult mice were treated with vehicle or tamoxifen and euthanized
      at 12 or 24 weeks postinjection. Compared with vehicle-treated controls, kidneys
      with tamoxifen-induced Wnt1 expression from proximal tubules displayed
      interstitial myofibroblast activation and proliferation and increased matrix
      protein production. PDGF receptor beta-positive myofibroblasts isolated from
      these kidneys exhibited increased canonical Wnt target gene expression compared
      with controls. Notably, fibrotic kidneys had no evidence of inflammatory cytokine
      expression, leukocyte infiltration, or epithelial injury, despite the close
      histologic correlation of each with CKD. These results provide the first example
      of noninflammatory renal fibrosis. The fact that epithelial-derived Wnt ligand is
      sufficient to drive interstitial fibrosis provides strong support for the
      maladaptive repair hypothesis in the AKI to CKD transition. 

PMID- 26204902
TI  - Progressive Hearing Loss and Head Trauma in Enlarged Vestibular Aqueduct: A
      Systematic Review and Meta-analysis.
AB  - OBJECTIVE: Enlarged vestibular aqueduct is the most common radiographically
      identified cause of congenital sensorineural hearing loss and is frequently
      progressive. Imaging is often ordered during the workup of children with
      congenital sensorineural hearing loss in part to identify enlarged vestibular
      aqueduct given concern for progression with head trauma. However, this
      association has not been systematically evaluated. We aimed to determine the rate
      of progression and association with head trauma in individuals with enlarged
      vestibular aqueduct. DATA SOURCES: Systematic review of primary studies
      identified through PubMed, Embase, Cochrane, and Web of Science. REVIEW METHODS:
      Meta-analysis was performed on patient-level data describing enlarged vestibular
      aqueduct, progressive sensorineural hearing loss, and head trauma extracted from
      articles identified on systematic review according to PRISMA guidelines. RESULTS:
      Twenty-three studies (1115 ears with enlarged vestibular aqueduct) met inclusion
      criteria. Progressive sensorineural hearing loss was found in 39.6% of ears, with
      trauma-associated progression in 12%. Limited case-control data show no
      difference in the incidence of progression between patients with and without head
      trauma. CONCLUSIONS: Long-term progressive sensorineural hearing loss is common
      in enlarged vestibular aqueduct, but its association with head trauma is not
      strongly supported.

PMID- 26204901
TI  - Impact of nanosilver on various DNA lesions and HPRT gene mutations - effects of
      charge and surface coating.
AB  - BACKGROUND: The main goal of this research was to study the interactions of a
      fully characterized set of silver nanomaterials (Ag ENMs) with cells in vitro,
      according to the standards of Good Laboratory Practices (GLP), to assure the
      quality of nanotoxicology research. We were interested in whether Ag ENMs
      synthesized by the same method, with the same size distribution, shape and
      specific surface area, but with different charges and surface compositions could
      give different biological responses. METHODS: A range of methods and toxicity
      endpoints were applied to study the impacts of interaction of the Ag ENMs with
      TK6 cells. As tests of viability, relative growth activity and trypan blue
      exclusion were applied. Genotoxicity was evaluated by the alkaline comet assay
      for detection of strand breaks and oxidized purines. The mutagenic potential of
      Ag ENMs was investigated with the in vitro HPRT gene mutation test on V79-4 cells
      according to the OECD protocol. Ag ENM agglomeration, dissolution as well as
      uptake and distribution within the cells were investigated as crucial aspects of
      Ag ENM toxicity. Ag ENM stabilizers were included in addition to positive and
      negative controls. RESULTS: Different cytotoxic effects were observed including
      membrane damage, cell cycle arrest and cell death. Ag ENMs also induced various
      kinds of DNA damage including strand breaks and DNA oxidation, and caused gene
      mutation. We found that positive Ag ENMs had greater impact on cyto- and
      genotoxicity than did Ag ENMs with neutral or negative charge, assumed to be
      related to their greater uptake into cells and to their presence in the nucleus
      and mitochondria, implying that Ag ENMs might induce toxicity by both direct and
      indirect mechanisms. CONCLUSION: We showed that Ag ENMs could be cytotoxic,
      genotoxic and mutagenic. Our experiments with the HPRT gene mutation assay
      demonstrated that surface chemical composition plays a significant role in Ag ENM
      toxicity.

PMID- 26204903
TI  - Combined serial analysis of gene expression and transcription factor binding site
      prediction identifies novel-candidate-target genes of Nr2e1 in neocortex
      development.
AB  - BACKGROUND: Nr2e1 (nuclear receptor subfamily 2, group e, member 1) encodes a
      transcription factor important in neocortex development. Previous work has shown
      that nuclear receptors can have hundreds of target genes, and bind more than 300
      co-interacting proteins. However, recognition of the critical role of Nr2e1 in
      neural stem cells and neocortex development is relatively recent, thus the
      molecular mechanisms involved for this nuclear receptor are only beginning to be
      understood. Serial analysis of gene expression (SAGE), has given researchers both
      qualitative and quantitative information pertaining to biological processes.
      Thus, in this work, six LongSAGE mouse libraries were generated from laser
      microdissected tissue samples of dorsal VZ/SVZ (ventricular zone and
      subventricular zone) from the telencephalon of wild-type (Wt) and Nr2e1-null
      embryos at the critical development ages E13.5, E15.5, and E17.5. We then used a
      novel approach, implementing multiple computational methods followed by
      biological validation to further our understanding of Nr2e1 in neocortex
      development. RESULTS: In this work, we have generated a list of 1279 genes that
      are differentially expressed in response to altered Nr2e1 expression during in
      vivo neocortex development. We have refined this list to 64 candidate direct
      targets of NR2E1. Our data suggested distinct roles for Nr2e1 during different
      neocortex developmental stages. Most importantly, our results suggest a possible
      novel pathway by which Nr2e1 regulates neurogenesis, which includes Lhx2 as one
      of the candidate direct-target genes, and SOX9 as a co-interactor. CONCLUSIONS:
      In conclusion, we have provided new candidate interacting partners and numerous
      well-developed testable hypotheses for understanding the pathways by which Nr2e1
      functions to regulate neocortex development.

PMID- 26204904
TI  - Efficacy of tacrolimus and clobetasol in the treatment of oral lichen planus: a
      systematic review and meta-analysis.
AB  - This study was carried out to assess and compare the efficacy of tacrolimus and
      clobetasol in the treatment of oral lichen planus (OLP). The Cochrane Central
      Register of Controlled Trials, PubMed, Scopus, Science Direct, Springer Journals,
      and Elsevier databases were searched using specific keywords relevant to the
      research question for articles published from 1998 to December 31, 2012. Finally,
      15 articles that assessed the effects of tacrolimus, clobetasol, and pimecrolimus
      on improvements in OLP were reviewed. In addition, a meta-analysis of odds ratios
      (ORs) was carried out for data in 10 of the 15 articles. The results showed that
      the ORs for improvements in OLP in patients taking clobetasol or tacrolimus,
      compared with those taking placebo or other drugs, were 1.19 and 8.00,
      respectively. It appears that topical tacrolimus is an effective alternative to
      topical clobetasol and may be considered as a first-line therapy in the
      management of OLP. 

PMID- 26204905
TI  - Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for
      colorectal cancer: choosing the right candidates.

PMID- 26204906
TI  - Nintedanib in combination with docetaxel for second-line treatment of advanced
      non-small-cell lung cancer.
AB  - Non-small lung cancer (NSCLC) is a lethal malignancy when diagnosed in advanced
      stage. The evolution of chemotherapy and the development of agents targeting
      certain molecular pathways involved in tumor progression improved the prognosis.
      Nintedanib is a new tyrosine kinase inhibitor, which exerts its activity by
      blocking VEGF, FGF and PDGF receptors and inhibits the angiogenic signaling by
      preventing receptor dimerization. Several Phase I and II studies proved its
      safety and efficacy in diverse solid tumors. In patients with advanced NSCLC, the
      administration of nintedanib may offer an additional chemotherapy benefit in
      terms of response rate, progression-free survival and overall survival
      particularly in patients with adenocarcinoma histology, with manageable toxicity.
      Here, we present an analytical review of literature regarding nintedanib and we
      focus on its particular importance in NSCLC treatment. 

PMID- 26204907
TI  - The diagnostic and prognostic role of liquid-based cytology: are we ready to
      monitor therapy and resistance?
AB  - Here, we evaluate the diagnostic and prognostic role of liquid-based cytology
      (LBC) in different body lesions, including thyroid, lung, effusions and malignant
      breast lesions. LBC has gained consensus after being applied to both non
      gynecologic and fine-needle aspiration cytology. Although some remain sceptical
      regarding the diagnostic efficacy of LBC, mainly when used alone, in recent
      years, good results have been obtained as long as it showed a high diagnostic
      accuracy. Here, we discuss the additional possibility of storing material for the
      application of ancillary techniques (immunocytochemistry-molecular analysis) with
      several diagnostic and prognostic advantages, which may pave the way for the
      challenging evaluation of both monitoring responses to treatment and resistance
      to targeted therapies in thyroid, lung, breast carcinoma or malignant effusions.
      Furthermore, it provides the use of several molecular spots as specific targets
      for personalized therapy. 

PMID- 26204908
TI  - Differences in levels of physical activity between White and South Asian
      populations within a healthcare setting: impact of measurement type in a cross
      sectional study.
AB  - OBJECTIVE: We investigate differences between White and South Asian (SA)
      populations in levels of objectively measured and self-reported physical
      activity. DESIGN: Cross-sectional study. SETTING: Leicestershire, UK, 2010-2011.
      PARTICIPANTS: Baseline data were pooled from two diabetes prevention trials that
      recruited a total of 4282 participants from primary care with a high risk score
      for type 2 diabetes. For this study, 2843 White (age=64+/-8, female=37%) and 243
      SA (age=58+/-9, female=34%) participants had complete physical activity data and
      were included in the analysis. OUTCOME MEASURES: Moderate-intensity to vigorous
      intensity physical activity (MVPA) and walking activity were measured using the
      International Physical Activity Questionnaire (IPAQ), and a combination of
      piezoelectric pedometer (NL-800) and accelerometer (Actigraph GT3X) were used to
      objectively measure physical activity. RESULTS: Compared to White participants,
      SA participants self-reported less MVPA (30 vs 51 min/day; p<0.001) and walking
      activity (11 vs 17 min/day; P=0.001). However, there was no difference in
      objectively measured ambulatory activity (5992 steps/day vs 6157 steps/day;
      p=0.75) or in time spent in MVPA (18.0 vs 21.5 min/day; p=0.23). Results were
      largely unaffected when adjusted for age, sex and social deprivation. Compared to
      accelerometer data, White participants overestimated their time in MVPA by 51
      min/day and SA participants by 21 min/day. CONCLUSIONS: SA and White groups
      undertook similar levels of physical activity when measured objectively despite
      self-reported estimates being around 40% lower in the SA group. This emphasises
      the limitations of comparing self-reported lifestyle measures across different
      populations and ethnic groups. TRIAL REGISTRATION NUMBER: Reports baseline data
      from: Walking Away from Type 2 Diabetes (ISRCTN31392913) and Let's Prevent
      Diabetes (NCT00677937).

PMID- 26204909
TI  - Socioeconomic determinants of risk of harmful alcohol drinking among people aged
      50 or over in England.
AB  - OBJECTIVES: This paper looks into the socioeconomic determinants of risk of
      harmful alcohol drinking and of the transitions between risk categories over time
      among the population aged 50 or over in England. SETTING: Community-dwellers
      across England. PARTICIPANTS: Respondents to the English Longitudinal Survey of
      Ageing, waves 4 and 5. RESULTS: (Confidence level at 95% or higher, except when
      stated): ? Higher risk drinking falls with age and there is a non-linear
      association between age and risk for men, peaking in their mid-60s. ? Retirement
      and income are positively associated with a higher risk for women but not for
      men. ? Education and smoking are positively associated for both sexes. ?
      Loneliness and depression are not associated. ? Caring responsibilities reduce
      risk among women. ? Single, separated or divorced men show a greater risk of
      harmful drinking (at 10% confidence level). ? For women, being younger and having
      a higher income at baseline increase the probability of becoming a higher risk
      alcohol drinker over time. ? For men, not eating healthily, being younger and
      having a higher income increase the probability of becoming a higher risk alcohol
      drinker. Furthermore, the presence of children living in the household, being
      lonely, being older and having a lower income are associated with ceasing to be a
      higher risk alcohol drinker over time. CONCLUSIONS: Several socioeconomic factors
      found to be associated with high-risk alcohol consumption behaviour among older
      people would align with those promoted by the 'successful ageing' policy
      framework.

PMID- 26204910
TI  - Under-reporting of maternal and perinatal adverse events in New Zealand.
AB  - OBJECTIVES: To determine the proportion of maternal and perinatal mortality and
      morbidity cases, identified by the Perinatal and Maternal Mortality Review
      Committee (PMMRC), that are also reported within the annual serious adverse
      events (SAEs) reports published by the Health Quality and Safety Commission
      (HQSC). SETTING: Nationally collated data from the PMMRC and HQSC, New Zealand.
      PARTICIPANTS: Analysis of maternal and perinatal mortality and morbidity data
      2009-2012. INTERVENTIONS: Every SAE report published by the HQSC from 2009 to
      2012 was scrutinised for maternal and perinatal cases using the case history
      provided by district health boards (DHB). Further detail of each case was
      requested from each DHB to establish whether they had been identified as maternal
      or perinatal mortalities or morbidities by the PMMRC. PRIMARY OUTCOME MEASURE:
      The proportion of maternal and perinatal mortality and morbidity cases identified
      by HQSC SAE reports, compared with PMMRC reporting. RESULTS: 58 maternal and
      perinatal SAEs were identified from the SAE reports 2009-2012. Of these, 50 fit
      under the PMMRC reporting definitions, all of which were also reported by the
      PMMRC. In the same time frame, the PMMRC captured 536 potentially avoidable
      maternal and perinatal mortalities and morbidities that fitted the HQSC SAE
      definition. Fewer than 9% of maternal and perinatal SAEs are captured by the HQSC
      SAE reporting process. CONCLUSIONS: The rate of maternal and perinatal adverse
      event reporting to the HQSC is low and not improving annually, compared with
      PMMRC reporting of eligible events. This is of concern as these events may not be
      adequately reviewed locally, and because the SAE report is considered a measure
      of quality by the DHBs and the HQSC. Currently, the reporting of SAEs to the HQSC
      cannot be considered a reliable way to monitor or improve the quality of
      maternity services provided in New Zealand.

PMID- 26204911
TI  - 'Including health in systems responsible for urban planning': a realist policy
      analysis research programme.
AB  - INTRODUCTION: Realist methods are increasingly being used to investigate complex
      public health problems. Despite the extensive evidence base clarifying the built
      environment as a determinant of health, there is limited knowledge about how and
      why land-use planning systems take on health concerns. Further, the body of
      research related to the wider determinants of health suffers from not using
      political science knowledge to understand how to influence health policy
      development and systems. This 4-year funded programme of research investigates
      how the land-use planning system in New South Wales, Australia, incorporates
      health and health equity at multiple levels. METHODS AND ANALYSIS: The programme
      uses multiple qualitative methods to develop up to 15 case studies of different
      activities of the New South Wales land-use planning system. Comparison cases from
      other jurisdictions will be included where possible and useful. Data collection
      includes publicly available documentation and purposively sampled stakeholder
      interviews and focus groups of up to 100 participants across the cases. The units
      of analysis in each case are institutional structures (rules and mandates
      constraining and enabling actors), actors (the stakeholders, organisations and
      networks involved, including health-focused agencies), and ideas (policy content,
      information, and framing). Data analysis will focus on and develop propositions
      concerning the mechanisms and conditions within and across each case leading to
      inclusion or non-inclusion of health. Data will be refined using additional
      political science and sociological theory. Qualitative comparative analysis will
      compare cases to develop policy-relevant propositions about the necessary and
      sufficient conditions needed to include health issues. ETHICS AND DISSEMINATION:
      Ethics has been approved by Sydney University Human Research Ethics Committee
      (2014/802 and 2015/178). Given the nature of this research we will incorporate
      stakeholders, often as collaborators, throughout. We outline our research
      translation strategies following best practice approaches.

PMID- 26204912
TI  - Successful treatment of cutaneous leishmaniasis of the ear with oral fluconazole.

PMID- 26204913
TI  - Outcome of adefovir add-on lamivudine rescue therapy of up to 5 years in patients
      with lamivudine-resistant chronic hepatitis B.
AB  - BACKGROUND AND AIM: We investigated the long-term efficacy of adefovir add-on
      lamivudine rescue therapy in lamivudine-resistant chronic hepatitis B and the
      optimal cutoff hepatitis B virus (HBV) DNA level that predicts complete
      virological response (CVR) among patients without CVR after 1 year of treatment.
      METHODS: We reviewed 167 lamivudine-resistant chronic hepatitis B patients who
      received adefovir add-on rescue therapy for up to 5 years. Multivariate analysis,
      area under the receiver operating characteristic curves, and Youden index were
      used. RESULTS: Median age was 47.0 years; 112 patients were male. Median baseline
      HBV DNA level was 6.6 log10 IU/mL; hepatitis B e antigen was positive in 130
      (77.4%) patients. Five-year CVR, alanine aminotransferase normalization,
      hepatitis B e antigen seroconversion, and adefovir resistance rates were 86.9%,
      92.5%, 16.7%, and 6.0%, respectively. One-year HBV DNA level independently
      associated with CVR. Optimal cutoff HBV DNA level to predict CVR among patients
      who failed to achieve CVR at 1 year was 800 IU/mL (area under receiver operating
      characteristic curve 0.752; sensitivity 49.3%, specificity 93.5%). During the 5
      year treatment, 92.1% of patients with favorable response (HBV DNA < 800 IU/mL at
      1 year) achieved CVR; 45.6% achieved CVR among suboptimal responders (HBV DNA >=
      800 IU/mL at 1 year) (P < 0.001). CONCLUSION: Complete virological response or
      HBV DNA level < 800 IU/mL after 1 year adefovir add-on lamivudine rescue therapy
      can favorably predict CVR.

PMID- 26204915
TI  - Mutant vascular actin is a TAAD misbehaving.

PMID- 26204914
TI  - Optogenetic determination of the myocardial requirements for extrasystoles by
      cell type-specific targeting of ChannelRhodopsin-2.
AB  - Extrasystoles lead to several consequences, ranging from uneventful palpitations
      to lethal ventricular arrhythmias, in the presence of pathologies, such as
      myocardial ischemia. The role of working versus conducting cardiomyocytes, as
      well as the tissue requirements (minimal cell number) for the generation of
      extrasystoles, and the properties leading ectopies to become arrhythmia triggers
      (topology), in the normal and diseased heart, have not been determined directly
      in vivo. Here, we used optogenetics in transgenic mice expressing
      ChannelRhodopsin-2 selectively in either cardiomyocytes or the conduction system
      to achieve cell type-specific, noninvasive control of heart activity with high
      spatial and temporal resolution. By combining measurement of optogenetic tissue
      activation in vivo and epicardial voltage mapping in Langendorff-perfused hearts,
      we demonstrated that focal ectopies require, in the normal mouse heart, the
      simultaneous depolarization of at least 1,300-1,800 working cardiomyocytes or 90
      160 Purkinje fibers. The optogenetic assay identified specific areas in the heart
      that were highly susceptible to forming extrasystolic foci, and such properties
      were correlated to the local organization of the Purkinje fiber network, which
      was imaged in three dimensions using optical projection tomography.
      Interestingly, during the acute phase of myocardial ischemia, focal ectopies
      arising from this location, and including both Purkinje fibers and the
      surrounding working cardiomyocytes, have the highest propensity to trigger
      sustained arrhythmias. In conclusion, we used cell-specific optogenetics to
      determine with high spatial resolution and cell type specificity the requirements
      for the generation of extrasystoles and the factors causing ectopies to be
      arrhythmia triggers during myocardial ischemia. 

PMID- 26204916
TI  - From intrinsically disordered protein to context-dependent folding: The alpha
      synuclein tetramer is teased out of hiding.

PMID- 26204917
TI  - Reactive oxygen species signal chloroplasts to extend themselves.

PMID- 26204918
TI  - Mitochondrial abnormalities in the myofibrillar myopathies.
AB  - Myofibrillar myopathies are a genetically diverse group of skeletal muscle
      disorders, with distinctive muscle histopathology. Causative mutations have been
      identified in the genes MYOT, LDB3, DES, CRYAB, FLNC, BAG3, DNAJB6, FHL1, PLEC
      and TTN, which encode proteins which either reside in the Z-disc or associate
      with the Z-disc. Mitochondrial abnormalities have been described in muscle from
      patients with a myofibrillar myopathy. We reviewed the literature to determine
      the extent of mitochondrial dysfunction in each of the myofibrillar myopathy
      subtypes. Abnormal mitochondrial distribution is a frequent finding in each of
      the subtypes, but a high frequency of COX-negative or ragged red fibres, a
      characteristic finding in some of the conventional mitochondrial myopathies, is a
      rare finding. Few in vitro studies of mitochondrial function have been performed
      in affected patients. 

PMID- 26204919
TI  - Accumulated dose to the rectum, measured using dose-volume histograms and dose
      surface maps, is different from planned dose in all patients treated with
      radiotherapy for prostate cancer.
AB  - OBJECTIVE: We sought to calculate accumulated dose (DA) to the rectum in patients
      treated with radiotherapy for prostate cancer. We were particularly interested in
      whether dose-surface maps (DSMs) provide additional information to dose-volume
      histograms (DVHs). METHODS: Manual rectal contours were obtained for kilovoltage
      and daily megavoltage CT scans for 10 participants from the VoxTox study (380
      scans). Daily delivered dose recalculation was performed using a ray-tracing
      algorithm. Delivered DVHs were summated to create accumulated DVHs. The rectum
      was considered as a cylinder, cut and unfolded to produce daily delivered DSMs;
      these were summated to produce accumulated DSMs. RESULTS: Accumulated dose
      volumes were different from planned in all participants. For one participant, all
      DA levels were higher and all volumes were larger than planned. For four
      participants, all DA levels were lower and all volumes were smaller than planned.
      For each of these four participants, >=1% of pixels on the accumulated DSM
      received >=5 Gy more than had been planned. CONCLUSION: Differences between
      accumulated and planned dose-volumes were seen in all participants. DSMs were
      able to identify differences between DA and planned dose that could not be
      appreciated from the DVHs. Further work is needed to extract the dose data
      embedded in the DSMs. These will be correlated with toxicity as part of the
      VoxTox Programme. ADVANCES IN KNOWLEDGE: DSMs are able to identify differences
      between DA and planned dose that cannot be appreciated from DVHs alone and should
      be incorporated into future studies investigating links between DA and toxicity.

PMID- 26204920
TI  - Usability evaluation and adaptation of the e-health Personal Patient Profile
      Prostate decision aid for Spanish-speaking Latino men.
AB  - BACKGROUND: The Personal Patient Profile-Prostate (P3P), a web-based decision
      aid, was demonstrated to reduce decisional conflict in English-speaking men with
      localized prostate cancer early after initial diagnosis. The purpose of this
      study was to explore and enhance usability and cultural appropriateness of a
      Spanish P3P by Latino men with a diagnosis of prostate cancer. METHODS: P3P was
      translated to Spanish and back-translated by three native Spanish-speaking
      translators working independently. Spanish-speaking Latino men with a diagnosis
      of localized prostate cancer, who had made treatment decisions in the past 24
      months, were recruited from two urban clinical care sites. Individual cognitive
      interviews were conducted by two bilingual research assistants as each
      participant used the Spanish P3P. Notes of user behavior, feedback, and answers
      to direct questions about comprehension, usability and perceived usefulness were
      analyzed and categorized. RESULTS: Seven participants with a range of education
      levels identified 25 unique usability issues in navigation, content comprehension
      and completeness, sociocultural appropriateness, and methodology. Revisions were
      prioritized to refine the usability and cultural and linguistic appropriateness
      of the decision aid. CONCLUSIONS: Usability issues were discovered that are
      potential barriers to effective decision support. Successful use of decision aids
      requires adaptation and testing beyond translation. Our findings led to revisions
      further refining the usability and linguistic and cultural appropriateness of
      Spanish P3P.

PMID- 26204921
TI  - Towards more drug-like proteomimetics: two-faced, synthetic alpha-helix mimetics
      based on a purine scaffold.
AB  - Mimicry of two faces of an alpha-helix might yield more potent and more selective
      inhibitors of aberrant, helix-mediated protein-protein interactions (PPI).
      Herein, we demonstrate that a 2,6,9-tri-substituted purine is capable of
      disrupting the Mcl-1-Bak-BH3 PPI through effective mimicry of key residues on
      opposing faces of the Bak-BH3 alpha-helix. 

PMID- 26204922
TI  - Fibrosis impairs the formation of new myofibers in the soft palate after injury.
AB  - Muscle repair is a crucial component of palatoplasty but little is known about
      muscle regeneration after cleft palate repair. We hypothesized that the formation
      of new myofibers is hampered by collagen accumulation after experimental injury
      of the soft palate of rats. One-millimeter excisional defects were made in the
      soft palates of 32 rats. The wound area was evaluated after 3, 7, 28, and 56 days
      using azocarmine G and aniline blue to stain for collagen and
      immunohistochemistry to identify myofibroblasts and to monitor skeletal muscle
      differentiation. To evaluate age effects, 16 unwounded animals were evaluated at
      3 and 56 days. Staining was quantified by image analysis, and one-way ANOVA was
      used for the statistical analysis. At day 56, the area percentage of collagen
      rich tissue was higher in the injured palatal muscles (46.7 +/- 6.9%) than in
      nonwounded controls (15.9 +/- 1.0%, p < 0.05). Myofibroblasts were present in the
      injured muscles at days 3 and 7 only. The numbers of proliferating and
      differentiating myoblasts within the wound area were greater at day 7 (p < 0.05),
      but only a few new myofibers had formed by 56 days. No age effects were found.
      The results indicate that surgical wounding of the soft palate results in muscle
      fibrosis. Although activated satellite cells migrated into the wound area, no new
      myofibers formed. Thus, regeneration and function of the soft palate muscles
      after injury may be improved by regenerative medicine approaches.

PMID- 26204923
TI  - Widespread noncoding circular RNAs in plants.
AB  - A large number of noncoding circular RNAs (circRNAs) with regulatory potency have
      been identified in animals, but little attention has been given to plant
      circRNAs. We performed genome-wide identification of circRNAs in Oryza sativa and
      Arabidopsis thaliana using publically available RNA-Seq data, analyzed and
      compared features of plant and animal circRNAs. circRNAs (12037 and 6012) were
      identified in Oryza sativa and Arabidopsis thaliana, respectively, with 56%
      (10/18) of the sampled rice exonic circRNAs validated experimentally. Parent
      genes of over 700 exonic circRNAs were orthologues between rice and Arabidopsis,
      suggesting conservation of circRNAs in plants. The introns flanking plant
      circRNAs were much longer than introns from linear genes, and possessed less
      repetitive elements and reverse complementary sequences than the flanking introns
      of animal circRNAs. Plant circRNAs showed diverse expression patterns, and 27
      rice exonic circRNAs were found to be differentially expressed under phosphate
      sufficient and -starvation conditions. A significantly positive correlation was
      observed for the expression profiles of some circRNAs and their parent genes. Our
      results demonstrated that circRNAs are widespread in plants, revealed the common
      and distinct features of circRNAs between plants and animals, and suggested that
      circRNAs could be a critical class of noncoding regulators in plants. 

PMID- 26204924
TI  - 23-gauge transconjunctival vitrectomy in eyes with pre-existing functioning
      filtering blebs.
AB  - BACKGROUND: We investigated the outcome of 23-gauge transconjunctival pars plana
      vitrectomy (23G PPV) for the treatment of vitreoretinal disorder in patients with
      prior trabeculectomy. METHODS: We retrospectively reviewed medical records of 23G
      PPV in 11 eyes that had functioning filtering blebs after trabeculectomy. The
      main outcome measures were the visual acuity, intraocular pressure (IOP) and
      subconjunctival fluid height in bleb by anterior segment optical coherence
      tomography (OCT) before and after the surgery. RESULTS: Eyes that had 23G PPV
      showed improvement of visual acuity after the surgery (P =0.003). Mean IOP was
      13.82 mmHg before 23G PPV and 15.82 mmHg at 6 months postoperatively, which was
      statistically insignificant (P = 0.758). The bleb was observed before and after
      surgery using anterior segment OCT, and the difference in subconjunctival fluid
      was not statistically significant (P =0.172). CONCLUSIONS: 23G PPV did not
      adversely affect bleb function in eyes with prior trabeculectomy.

PMID- 26204926
TI  - Incidence and risk factors of herpes zoster among adult renal transplant
      recipients receiving universal antiviral prophylaxis.
AB  - BACKGROUND: Herpes zoster (HZ) is a significant cause of morbidity and
      complications in adult renal transplant recipients. We determined the incidence,
      complications and risk factors for the development of HZ after renal
      transplantation in a setting using universal antiviral prophylaxis. METHODS: The
      medical files of all adult renal transplants, performed between 2004 and 2008,
      were retrospectively reviewed to assess the clinical characteristics and risk
      factors of HZ. Incident cases of HZ were determined and the probability of
      developing post-transplant HZ for all subjects was calculated using the Kaplan
      Meier method. A multivariable Cox proportional hazards model was applied to
      assess the risk factors associated with the development of HZ. RESULTS: A total
      of 450 patients were eligible with a median follow up of 38 months. Twenty nine
      subjects (6.4%) developed HZ, the median time to onset was 18 months, only three
      of them (10.3%) required hospitalization, and none developed disseminated or
      visceral disease and death directly attributed to zoster. However, high rates of
      post-herpetic neuralgia (48.7%) were observed. Overall incidence was calculated
      at 20.6 cases per 1000 patient-years of follow-up. Following multivariate
      analysis, increased age >= 60 years old, positive pre-transplant history of
      varicella related disease and administration of rejection treatment conferred an
      increased risk of 4.00-fold (CI: 1.79-8.92), 16.00-fold (CI: 4.62-55.52), and
      5.57-fold (CI: 1.56-19.84) respectively, for the development of post-transplant
      zoster. CONCLUSIONS: HZ remains a common complication after renal transplantation
      in adults under current immunosuppession protocols and universal antiviral
      prophylaxis.

PMID- 26204925
TI  - Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of
      Wharton Jelly mesenchymal stem cell secretome?
AB  - INTRODUCTION: The use of human umbilical cord Wharton Jelly-derived mesenchymal
      stem cells (hWJ-MSCs) has been considered a new potential source for future safe
      applications in regenerative medicine. Indeed, the application of hWJ-MSCs into
      different animal models of disease, including those from the central nervous
      system, has shown remarkable therapeutic benefits mostly associated with their
      secretome. Conventionally, hWJ-MSCs are cultured and characterized under normoxic
      conditions (21 % oxygen tension), although the oxygen levels within tissues are
      typically much lower (hypoxic) than these standard culture conditions. Therefore,
      oxygen tension represents an important environmental factor that may affect the
      performance of mesenchymal stem cells in vivo. However, the impact of hypoxic
      conditions on distinct mesenchymal stem cell characteristics, such as the
      secretome, still remains unclear. METHODS: In the present study, we have examined
      the effects of normoxic (21 % O2) and hypoxic (5 % O2) conditions on the hWJ-MSC
      secretome. Subsequently, we address the impact of the distinct secretome in the
      neuronal cell survival and differentiation of human neural progenitor cells.
      RESULTS: The present data indicate that the hWJ-MSC secretome collected from
      normoxic and hypoxic conditions displayed similar effects in supporting neuronal
      differentiation of human neural progenitor cells in vitro. However, proteomic
      analysis revealed that the use of hypoxic preconditioning led to the upregulation
      of several proteins within the hWJ-MSC secretome. CONCLUSIONS: Our results
      suggest that the optimization of parameters such as hypoxia may lead to the
      development of strategies that enhance the therapeutic effects of the secretome
      for future regenerative medicine studies and applications.

PMID- 26204927
TI  - Diagnostic imaging of cervical intraepithelial neoplasia based on hematoxylin and
      eosin fluorescence.
AB  - BACKGROUND: Pathological classification of cervical intraepithelial neoplasia
      (CIN) is problematic as it relies on subjective criteria. We developed an imaging
      method that uses spectroscopy to assess the fluorescent intensity of cervical
      biopsies derived directly from hematoxylin and eosin (H&E) stained tissues.
      METHODS: Archived H&E slides were identified containing normal cervical tissue,
      CIN I, and CIN III cases, from a Community Hospital and an Academic Medical
      Center. Cases were obtained by consensus review of at least 2 senior
      pathologists. Images from H&E slides were captured first with bright field
      illumination and then with fluorescent illumination. We used a Zeiss Axio
      Observer Z1 microscope and an AxioVision 4.6.3-AP1 camera at excitation
      wavelength of 450-490 nm with emission captured at 515-565 nm. The 32-bit
      grayscale fluorescence images were used for image analysis. RESULTS: We reviewed
      108 slides: 46 normal, 33 CIN I and 29 CIN III. Fluorescent intensity increased
      progressively in normal epithelial tissue as cells matured and advanced from the
      basal to superficial regions of the epithelium. In CIN I cases this change was
      less prominent as compared to normal. In high grade CIN lesions, there was a
      slight or no increase in fluorescent intensity. All groups examined were
      statistically different. CONCLUSION: Presently, there are no markers to help in
      classification of CIN I-III lesions. Our imaging method may complement standard
      H&E pathological review and provide objective criteria to support the CIN
      diagnosis.

PMID- 26204928
TI  - Income-related inequalities in health care utilization in Mongolia, 2007/2008
      2012.
AB  - BACKGROUND: Although health strategies and policies have addressed equitable
      distribution of health care in Mongolia, few studies have been conducted on this
      topic. Rapid socio-economic changes have recently occurred; however, there is no
      evidence as to how horizontal inequity has changed. The aim of this paper is to
      evaluate income related-inequalities in health care utilizations and their
      changes between 2007/2008 and 2012 in Mongolia. METHODS: The data used in this
      study was taken from the nationwide cross-sectional data sets, the Household
      Socio-Economic Survey, collected in 2007/2008 and 2012 by the National
      Statistical Office of Mongolia. We employed the Erreygers' concentration index to
      measure inequality in health service utilization. Horizontal inequity was
      estimated by a difference between actual and predicted use of health services
      using the indirect standardization method. RESULTS: The results show that the
      concentration indices for tertiary level, private outpatient and inpatient
      services were significantly positive, the contrary for family group practice/soum
      hospital outpatient services, in both years. After controlling for need, pro-rich
      inequity (p < 0.01) was observed in the tertiary level, private outpatient, and
      general inpatient, services in both years. Pro-poor inequity (p < 0.01) existed
      in family group practice/soum hospital outpatient services in both years. Degrees
      of inequity in tertiary level hospital and private hospital outpatient services
      became more pro-rich, whereas in family group practice/soum hospital outpatient
      services became more pro-poor from 2007/2008 to 2012. Pro-rich inequity in
      inpatient services remained the same from 2007/2008 to 2012. CONCLUSIONS:
      Equitable distribution of health care has been well documented in health
      strategies and policies; however, the degree of inequity in delivery of health
      services has a tendency to increase in Mongolia. Therefore, there is a need to
      consider implementation issues of the strategies and refocus on policy
      prioritizations. It is necessary to strengthen primary health care services,
      particularly by diminishing obstacles for lower income and higher need groups.

PMID- 26204929
TI  - Long non-coding RNAs: biomarkers for acute leukaemia subtypes.

PMID- 26204930
TI  - Properties of vocalization- and gesture-combinations in the transition to first
      words.
AB  - Gestures and vocal elements interact from the early stages of language
      development, but the role of this interaction in the language learning process is
      not yet completely understood. The aim of this study is to explore gestural
      accompaniment's influence on the acoustic properties of vocalizations in the
      transition to first words. Eleven Spanish children aged 0;9 to 1;3 were observed
      longitudinally in a semi-structured play situation with an adult. Vocalizations
      were analyzed using several acoustic parameters based on those described by Oller
      et al. (2010). Results indicate that declarative vocalizations have fewer
      protosyllables than imperative ones, but only when they are produced with a
      gesture. Protosyllables duration and f(0) are more similar to those of mature
      speech when produced with pointing and declarative function than when produced
      with reaching gestures and imperative purposes. The proportion of canonical
      syllables produced increases with age, but only when combined with a gesture. 

PMID- 26204931
TI  - U-shaped relationship between early blood glucose and mortality in critically ill
      children.
AB  - BACKGROUND: The aims of this study are to evaluate the relationship between early
      blood glucose concentrations and mortality and to define a 'safe range' of blood
      glucose concentrations during the first 24 h after pediatric intensive care unit
      (PICU) admission with the lowest risk of mortality. We further determine whether
      associations exist between PICU mortality and early hyperglycemia and
      hypoglycemia occurring within 24 h of PICU admission, even after adjusting for
      illness severity assessed by the pediatric risk of mortality III (PRISM III)
      score. METHODS: This retrospective cohort study included patients admitted to
      PICU between July 2008 and June 2011 in a tertiary teaching hospital. Both the
      initial admission glucose values and the mean glucose values over the first 24 h
      after PICU admission were analyzed. RESULTS: Of the 1349 children with at least
      one blood glucose value taken during the first 24 h after admission, 129 died
      during PICU stay. When analyzing both the initial admission and mean glucose
      values during the first 24 h after admission, the mortality rate was compared
      among children with glucose concentrations <= 65, 65-90, 90-110, 110-140, 140
      200, and >200 mg/dL (<= 3.6, 3.6-5.0, 5.0-6.1, 6.1-7.8, 7.8-11.1, and >11.1
      mmol/L). Children with glucose concentrations <= 65 mg/dL (3.6 mmol/L) and >200
      mg/dL (11.1 mmol/L) had significantly higher mortality rates, indicating a U
      shaped relationship between glucose concentrations and mortality. Blood glucose
      concentrations of 110-140 mg/dL (6.1-7.8 mmol/L), followed by 90-110 mg/dL (5.0
      6.1 mmol/L), were associated with the lowest risk of mortality, suggesting that a
      'safe range' for blood glucose concentrations during the first 24 h after
      admission in critically ill children exists between 90 and 140 mg/dL (5.0 and 7.8
      mmol/L). The odds ratios of early hyperglycemia (>140 mg/dL [7.8 mmol/L]) and
      hypoglycemia (<= 65 mg/dL [3.6 mmol/L]) being associated with increased risk of
      mortality were 4.13 and 15.13, respectively, compared to those with mean glucose
      concentrations of 110-140 mg/dL (6.1-7.8 mmol/L) (p <0.001). The association
      remained significant after adjusting for PRISM III scores (p <0.001).
      CONCLUSIONS: There was a U-shaped relationship between early blood glucose
      concentrations and PICU mortality in critically ill children. Both early
      hyperglycemia and hypoglycemia were associated with mortality, even after
      adjusting for illness severity.

PMID- 26204932
TI  - Impact of socio-economic status on hospital length of stay following injury: a
      multicenter cohort study.
AB  - BACKGROUND: Injury is second only to cardiovascular disease in terms of acute
      care costs in North America. One key to improving injury care efficiency is to
      generate knowledge on the determinants of resource use. Socio-economic status
      (SES) is a documented risk factor for injury severity and mortality but its
      impact on length of stay (LOS) for injury admissions is unknown. This study aimed
      to examine the relationship between SES and LOS following injury. This
      multicenter retrospective cohort study was based on adults discharged alive from
      any trauma center (2007-2012; 57 hospitals; 65,486 patients) in a Canadian
      integrated provincial trauma system. SES was determined using ecological indices
      of material and social deprivation. Mean differences in LOS adjusted for age,
      gender, comorbidities, and injury severity were generated using multivariate
      linear regression. RESULTS: Mean LOS was 13.5 days. Patients in the highest
      quintile of material/social deprivation had a mean LOS 0.5 days (95 % CI 0.1
      0.9)/1.4 days (1.1-1.8) longer than those in the lowest quintile. Patients in the
      highest quintiles of both social and material deprivation had a mean LOS 2.6 days
      (1.8-3.5) longer than those in the lowest quintiles. CONCLUSIONS: Results suggest
      that patients admitted for traumatic injury who suffer from high social and/or
      material deprivation have longer acute care LOS in a universal-access health care
      system. The reasons behind observed differences need to be further explored but
      may indicate that discharge planning should take patient SES into consideration.

PMID- 26204933
TI  - Erratum to: PREVENTT: preoperative intravenous iron to treat anaemia in major
      surgery: study protocol for a randomised controlled trial.

PMID- 26204935
TI  - Molecular weight growth in Titan's atmosphere: branching pathways for the
      reaction of 1-propynyl radical (H3CC=C) with small alkenes and alkynes.
AB  - The reaction of small hydrocarbon radicals (i.e.CN, C2H) with trace alkenes and
      alkynes is believed to play an important role in molecular weight growth and
      ultimately the formation of Titan's characteristic haze. Current photochemical
      models of Titan's atmosphere largely assume hydrogen atom abstraction or
      unimolecular hydrogen elimination reactions dominate the mechanism, in contrast
      to recent experiments that reveal significant alkyl radical loss pathways during
      reaction of ethynyl radical (C2H) with alkenes and alkynes. In this study, the
      trend is explored for the case of a larger ethynyl radical analogue, the 1
      propynyl radical (H3CC[triple bond, length as m-dash]C), a likely product from
      the high-energy photolysis of propyne in Titan's atmosphere. Using synchrotron
      vacuum ultraviolet photoionization mass spectrometry, product branching ratios
      are measured for the reactions of 1-propynyl radical with a suite of small
      alkenes (ethylene and propene) and alkynes (acetylene and d4-propyne) at 4 Torr
      and 300 K. Reactions of 1-propynyl radical with acetylene and ethylene form
      single products, identified as penta-1,3-diyne and pent-1-en-3-yne, respectively.
      These products form by hydrogen atom loss from the radical-adduct intermediates.
      The reactions of 1-propynyl radical with d4-propyne and propene form products
      from both hydrogen atom and methyl loss, (-H = 27%, -CH3 = 73%) and (-H = 14%, 
      CH3 = 86%), respectively. Together, these results indicate that reactions of
      ethynyl radical analogues with alkenes and alkynes form significant quantities of
      products by alkyl loss channels, suggesting that current photochemical models of
      Titan over predict both hydrogen atom production as well as the efficiency of
      molecular weight growth in these reactions. 

PMID- 26204934
TI  - Increased inflammation but similar physical composition and function in older
      aged, HIV-1 infected subjects.
AB  - BACKGROUND: Systemic immune activation (inflammation) and immunosenescence
      develop in some people with advancing age. This process, known as "inflamm
      aging," is associated with physical frailty and sarcopenia. Meanwhile, successful
      antiretroviral therapy has led to a growing number of older HIV-1-infected
      individuals who face both age-related and HIV-1-related inflammation, which may
      synergistically promote physical decline, including frailty and sarcopenia. The
      purpose of our study was to determine if inflammation during treated HIV-1
      infection worsens physical impairment in older individuals. METHODS: We
      determined the severity of HIV-associated inflammation and physical performance
      (strength and endurance) in 21 older HIV-infected individuals (54-69 years)
      receiving suppressive antiretroviral therapy, balanced for confounding variables
      including age, anthropometrics, and co-morbidities with 10 uninfected control
      individuals. Biomarkers for microbial translocation (lipopolysaccharide [LPS]),
      inflammation (soluble CD14 [sCD14], osteopontin, C-reactive protein [CRP],
      interleukin-6 [IL-6], soluble ICAM-1 [sICAM-1] and soluble VCAM-1 [sVCAM-1]), and
      coagulopathy (D-dimer) were assayed in plasma. Activation phenotypes of CD4(+)T
      cells, CD8(+) T cells and monocytes were measured by flow cytometry. Physical
      performance was measured by 400 m walking speed, a short physical performance
      battery [SPPB], and lower extremity muscle strength and fatigue. RESULTS: Overall
      physical function was similar in the uninfected and HIV-infected groups. Compared
      to uninfected individuals, the HIV-infected group had elevated levels of sCD14 (P
      < 0.001), CRP (P < 0.001) and IL-6 (P = 0.003) and an increased frequency of
      CD4(+) and CD8(+) T cells with an immunosenescent CD57(+) phenotype (P = 0.004
      and P = 0.043, respectively). Neither plasma inflammatory biomarkers nor CD57(+)
      T cells correlated with CD4(+) T cell counts. Furthermore, none of the elevated
      inflammatory biomarkers in the HIV-infected subjects were associated with any of
      the physical performance results. CONCLUSIONS: When age-related co-morbidities
      were carefully balanced between the uninfected and HIV-infected groups, no
      evidence of inflammation-associated physical impairment was detected. Despite
      careful balancing for age, BMI, medications and co-morbidities, the HIV-infected
      group still displayed evidence of significant chronic inflammation, including
      elevated sCD14, CRP, IL-6 and CD57(+) T cells, although the magnitude of this
      inflammation was unrelated to physical impairment.

PMID- 26204936
TI  - Paeoniflorin exerts a nephroprotective effect on concanavalin A-induced damage
      through inhibition of macrophage infiltration.
AB  - BACKGROUND: It is well established that macrophage infiltration is involved in
      concanavalin A (conA)-induced liver injury. However, the role of macrophages in
      conA-induced renal injury remains unknown. The aims of this study were to
      investigate macrophage infiltration in conA-induced renal injury and determine
      whether paeoniflorin (PF) could inhibit macrophage infiltration into the kidney.
      METHODS: BALB/C mice were pre-treated with or without PF 2 h (h) before conA
      injection. At 8 h after con A injection, all the mice were sacrificed; The liver
      and kidney histology were studied. The renal CD68 expression was detected by
      immunohistochemical and real-time PCR analysis. The level of expression of C-X-C
      chemokine receptor type 3 (CXCR3) was analyzed by western blot,
      immunohistochemical and real-time PCR. The pathophysiological involvement of
      CXCR3 in macrophage infiltration were investigated using dual-colour
      immunofluorescence microscopy. RESULTS: PF administration significantly reduced
      the elevated serum levels of alanine transaminase (ALT), blood urea nitrogen
      (BUN), creatinine (Cr) and the severity of liver and renal damage compared with
      that in the conA-vehicle group. PF administration inhibited the increase in renal
      IL1beta mRNA expression and concentration. Furthermore, immunohistochemical
      analysis showed that macrophages secreted CXCR3 in the kidneys of the conA
      vehicle mice. Immunofluorescence microscopy demonstrated CXCR3 bound tightly to C
      X-C motif ligand 11 (CXCL11) in the kidneys of the conA-vehicle mice and showed
      that PF treatment could suppress CXCR3/CXCL11 over-activation. CONCLUSIONS:
      Macrophage infiltration was a notable pathological change in the kidneys of conA
      treated mice. PF administration attenuated conA-induced renal damage, at least in
      part, by inhibiting the over-activated CXCR3/CXCL11 signal axis.

PMID- 26204937
TI  - ROCK activity and the Gbetagamma complex mediate chemotactic migration of mouse
      bone marrow-derived stromal cells.
AB  - INTRODUCTION: Bone marrow-derived stromal cells (BMSCs), also known as
      mesenchymal stem cells, are the focus of intensive efforts worldwide to elucidate
      their function and biology. Despite the importance of BMSC migration for their
      potential therapeutic uses, the mechanisms and signalling governing stem cell
      migration are still not fully elucidated. METHODS: We investigated and detailed
      the effects of MCP-1 activation on BMSCs by using inhibitors of G protein-coupled
      receptor alpha beta (GPCR alphabeta), ROCK (Rho-associated, coiled-coil
      containing protein kinase), and PI3 kinase (PI3K). The effects of MCP-1
      stimulation on intracellular signalling cascades were characterised by using
      immunoblotting and immunofluorescence. The effectors of MCP-1-mediated migration
      were investigated by using migration assays (both two-dimensional and three
      dimensional) in combination with inhibitors. RESULTS: We established the kinetics
      of the MCP-1-activated signalling cascade and show that this cascade correlates
      with cell surface re-localisation of chemokine (C motif) receptor 2 (CCR2) (the
      MCP-1 receptor) to the cell periphery following MCP-1 stimulation. We show that
      MCP-1-initiated signalling is dependent on the activation of betagamma subunits
      from the GPCR alphabetagamma complex. In addition, we characterise a novel role
      for PI3Kgamma signalling for the activation of both PAK and ERK following MCP-1
      stimulation. We present evidence that the Gbetagamma complex is responsible for
      PI3K/Akt, PAK, and ERK signalling induced by MCP-1 in BMSCs. Importantly, we
      found that, in BMSCs, inhibition of ROCK significantly inhibits MCP-1-induced
      chemotactic migration, in contrast to previous reports in other systems.
      CONCLUSIONS: Our results indicate differential chemotactic signalling in mouse
      BMSCs, which has important implications for the translation of in vivo mouse
      model findings into human trials. We identified novel components and interactions
      activated by MCP-1-mediated signalling, which are important for stem cell
      migration. This work has identified additional potential therapeutic targets that
      could be manipulated to improve BMSC delivery and homing.

PMID- 26204938
TI  - Diagnostic accuracy of left ventricular longitudinal function by speckle tracking
      echocardiography to predict significant coronary artery stenosis. A systematic
      review.
AB  - BACKGROUND: Patients evaluated for acute and chronic chest pain comprise a large,
      heterogeneous group that often provides diagnostic challenges. Although speckle
      tracking echocardiography (STE) has proved to have diagnostic value in acute
      coronary syndrome it is not commonly incorporated in everyday practice. The
      purpose of the present systematic review was to assess the diagnostic accuracy of
      left ventricular (LV) longitudinal function by STE to predict significant
      coronary artery stenosis (CAD+) or not (CAD-) verified by coronary angiography in
      patients with chest pain suspected to be of cardiac ischemic origin. METHODS: 4
      electronic databases; Embase, Medline, Cochrane and PubMed ahead-of print were
      searched for per 19.05.14. Only full-sized articles including >40 patients were
      selected. RESULTS: A total of 166 citations were identified, 16 full-size
      articles were assessed of which 6 were found eligible for this review. Of 781
      patients included 397 (60%) had CAD+. The overall weighted mean global
      longitudinal strain (GLS) was -17.2% (SD=2.6) among CAD+ vs. -19.2% (SD=2.8) in
      CAD- patients. Mean area under curve in 4 studies for predicting CAD+ ranged from
      0.68 to 0.80. The study cut-off levels for prediction of CAD+ in the ROC analysis
      varied between -17.4% and -19.7% with sensitivity from 51% to 81% and specificity
      between 58% and 81%. In 1 study GLS obtained during dobutamine stress
      echocardiography (DSE) had the best accuracy. Regional strain measurements were
      not uniform, but may have potential in detecting CAD. CONCLUSIONS: GLS
      measurements at rest only have modest diagnostic accuracy in predicting CAD+
      among patients presenting with acute or chronic chest pain. The results from
      regional strain, layer specific strain and DSE need to be verified in larger
      studies.

PMID- 26204944
TI  - Pemphigus vegetans presenting as a verrucous plaque on the finger.

PMID- 26204939
TI  - RUNX2 and the PI3K/AKT axis reciprocal activation as a driving force for tumor
      progression.
AB  - From the first reported role of the transcription factor RUNX2 in osteoblast and
      chondrocyte differentiation and migration to its involvement in
      promigratory/proinvasive behavior of breast, prostate, and thyroid cancer cells,
      osteosarcoma, or melanoma cells, RUNX2 currently emerges as a key player in
      metastasis. In this review, we address the interaction of RUNX2 with the PI3K/AKT
      signaling pathway, one of the critical axes controlling cancer growth and
      metastasis. AKT, either by directly phosphorylating/activating RUNX2 or
      phosphorylating/inactivating regulators of RUNX2 stability or activity,
      contributes to RUNX2 transcriptional activity. Reciprocally, the activation of
      the PI3K/AKT pathway by RUNX2 regulation of its different components has been
      described in non-transformed and transformed cells. This mutual activation in the
      context of cancer cells exhibiting constitutive AKT activation and high levels of
      RUNX2 might constitute a major driving force in tumor progression and
      aggressiveness.

PMID- 26204945
TI  - Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle
      Inhibition and Cell Death in Pancreatic Cancer Cells.
AB  - Pancreatic cancer is one of the most aggressive cancer entities, with an
      extremely poor 5-year survival rate. Therefore, novel therapeutic agents with
      specific modes of action are urgently needed. Marine organisms represent a
      promising source to identify new pharmacologically active substances. Secondary
      metabolites derived from marine algae are of particular interest. The present
      work describes cellular and molecular mechanisms induced by an HPLC-fractionated,
      hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus
      (Fv1). Treatment with Fv1 resulted in a strong inhibition of viability in various
      pancreatic cancer cell lines. This extract inhibited the cell cycle of
      proliferating cells due to the up-regulation of cell cycle inhibitors, shown on
      the mRNA (microarray data) and protein level. As a result, cells were dying in a
      caspase-independent manner. Experiments with non-dividing cells showed that
      proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1
      showed low cytotoxic activity against non-malignant resting T cells and
      terminally differentiated cells like erythrocytes. Interestingly, accelerated
      killing effects were observed in combination with inhibitors of autophagy. Our in
      vitro data suggest that Fv1 may represent a promising new agent that deserves
      further development towards clinical application. 

PMID- 26204946
TI  - Identification and Bioactivity of Compounds from the Mangrove Endophytic Fungus
      Alternaria sp.
AB  - Racemic new cyclohexenone and cyclopentenone derivatives, (+/-)-(4R*,5S*,6S*)-3
      amino-4,5,6-trihydroxy-2-methoxy-5-methyl-2-cyclohexen-1-one (1) and (+/-)
      (4S*,5S*)-2,4,5-trihydroxy-3-methoxy-4-methoxycarbonyl-5-methyl-2-cyclopenten-1
      one (2), and two new xanthone derivatives 4-chloro-1,5-dihydroxy-3-hydroxymethyl
      6-methoxycarbonyl-xanthen-9-one (3) and 2,8-dimethoxy-1,6-dimethoxycarbonyl
      xanthen-9-one (4), along with one known compound, fischexanthone (5), were
      isolated from the culture of the mangrove endophytic fungus Alternaria sp. R6.
      The structures of these compounds were elucidated by analysis of their MS (Mass),
      one and two dimensional NMR (nuclear magnetic resonance) spectroscopic data.
      Compounds 1 and 2 exhibited potent ABTS [2,2'-azino-bis(3-ethylbenzthiazoline-6
      sulphonic acid)] scavenging activities with EC50 values of 8.19 +/- 0.15 and
      16.09 +/- 0.01 MUM, respectively. In comparison to Triadimefon, compounds 2 and 3
      exhibited inhibitory activities against Fusarium graminearum with minimal
      inhibitory concentration (MIC) values of 215.52 and 107.14 MUM, respectively, and
      compound 3 exhibited antifungal activity against Calletotrichum musae with MIC
      value of 214.29 MUM. 

PMID- 26204947
TI  - Potential Antiviral Agents from Marine Fungi: An Overview.
AB  - Biodiversity of the marine world is only partially subjected to detailed
      scientific scrutiny in comparison to terrestrial life. Life in the marine world
      depends heavily on marine fungi scavenging the oceans of lifeless plants and
      animals and entering them into the nutrient cycle by. Approximately 150 to 200
      new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic
      compounds, are identified from marine fungi annually. In recent years, numerous
      investigations demonstrated the tremendous potential of marine fungi as a
      promising source to develop new antivirals against different important viruses,
      including herpes simplex viruses, the human immunodeficiency virus, and the
      influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium,
      Cladosporium, and Fusarium were subjected to compound isolation and antiviral
      studies, which led to an illustration of the strong antiviral activity of a
      variety of marine fungi-derived compounds. The present review strives to
      summarize all available knowledge on active compounds isolated from marine fungi
      with antiviral activity. 

PMID- 26204948
TI  - Structural Investigation of the Oligosaccharide Portion Isolated from the
      Lipooligosaccharide of the Permafrost Psychrophile Psychrobacter arcticus 273-4.
AB  - Psychrophilic microorganisms have successfully colonized all permanently cold
      environments from the deep sea to mountain and polar regions. The ability of an
      organism to survive and grow in cryoenviroments depends on a number of adaptive
      strategies aimed at maintaining vital cellular functions at subzero temperatures,
      which include the structural modifications of the membrane. To understand the
      role of the membrane in the adaptation, it is necessary to characterize the cell
      wall components, such as the lipopolysaccharides, that represent the major
      constituent of the outer membrane. The aim of this study was to investigate the
      structure of the carbohydrate backbone of the lipooligosaccharide (LOS) isolated
      from the cold-adapted Psychrobacter arcticus 273-4. The strain, isolated from a
      20,000-to-30,000-year-old continuously frozen permafrost in Siberia, was
      cultivated at 4  degrees C. The LOS was isolated from dry cells and analyzed by
      means of chemical methods. In particular, it was degraded either by mild acid
      hydrolysis or by hydrazinolysis and investigated in detail by (1)H and (13)C NMR
      spectroscopy and by ESI FT-ICR mass spectrometry. The oligosaccharide was
      characterized by the substitution of the heptose residue, usually linked to Kdo
      in the inner core, with a glucose, and for the unusual presence of N
      acetylmuramic acid. 

PMID- 26204949
TI  - Isolation and Total Synthesis of Stolonines A-C, Unique Taurine Amides from the
      Australian Marine Tunicate Cnemidocarpa stolonifera.
AB  - Cnemidocarpa stolonifera is an underexplored marine tunicate that only occurs on
      the tropical to subtropical East Coast of Australia, with only two pyridoacridine
      compounds reported previously. Qualitative analysis of the lead-like enhanced
      fractions of C. stolonifera by LC-MS dual electrospray ionization coupled with
      PDA and ELSD detectors led to the identification of three new natural products,
      stolonines A-C (1-3), belonging to the taurine amide structure class. Structures
      of the new compounds were determined by NMR and MS analyses and later verified by
      total synthesis. This is the first time that the conjugates of taurine with 3
      indoleglyoxylic acid, quinoline-2-carboxylic acid and beta-carboline-3-carboxylic
      acid present in stolonines A-C (1-3), respectively, have been reported. An
      immunofluorescence assay on PC3 cells indicated that compounds 1 and 3 increased
      cell size, induced mitochondrial texture elongation, and caused apoptosis in PC3
      cells. 

PMID- 26204950
TI  - Prevalence of depression and associated factors among Somali refugee at Melkadida
      camp, Southeast Ethiopia: a cross-sectional study.
AB  - BACKGROUND: Psychological distress, psychosomatic complaints and clinical mental
      disorders such as depression and post-traumatic stress disorder are highly
      prevalent among refugees than other populations. Even though there were several
      studies done on mental health of refugees globally, there is very few in Ethiopia
      regarding the mental health of these vulnerable populations. Thus we aimed at
      determining the prevalence of depression and identifying determinants of
      depression among refugees. METHODS: A community based cross-sectional multistage
      survey with 847 adult refugees was conducted in May 2014 at Melkadida camp,
      Southeast Ethiopia. Data were collected by face to face interviews on socio
      demographic by using structured questionnaire, level of exposure to trauma by
      Harvard Trauma Questionnaire and depression symptoms by using Patient Health
      Questionnaire. Data entry and clearance were carried out by EpInfo version 7 and
      analysis was carried out by Statistical Package for Social Sciences version-20
      software package. Data was examined using descriptive statistics and logistic
      regression, odds ratios and 95 % confidence intervals. RESULT: Over one third
      (38.3 %) of respondents met the symptoms criteria for depression. Gender, marital
      status, displaced previously as refugee, witnessing murderer of family or friend,
      lack of house or shelter and being exposed to increased number of cumulative
      traumatic events were significantly associated with depression among Somali
      refugees in Melkadida camp. CONCLUSION: The study revealed a relatively high
      prevalence of depression episode among refugees. Being female, divorced, deprived
      of shelter and witnessing the murder of family are most determinants of
      depression in refugees. Strengthening the clinical set up and establishing good
      referral linkage with mental health institutions is strongly recommended.

PMID- 26204951
TI  - Identification of the minimal cytolytic unit for streptolysin S and an expansion
      of the toxin family.
AB  - BACKGROUND: Streptolysin S (SLS) is a cytolytic virulence factor produced by the
      human pathogen Streptococcus pyogenes and other Streptococcus species. Related
      "SLS-like" toxins have been characterized in select strains of Clostridium and
      Listeria, with homologous clusters bioinformatically identified in a variety of
      other species. SLS is a member of the thiazole/oxazole-modified microcin (TOMM)
      family of natural products. The structure of SLS has yet to be deciphered and
      many questions remain regarding its structure-activity relationships. RESULTS: In
      this work, we assessed the hemolytic activity of a series of C-terminally
      truncated SLS peptides expressed in SLS-deficient S. pyogenes. Our data indicate
      that while the N-terminal poly-heterocyclizable (NPH) region of SLS substantially
      contributes to its bioactivity, the variable C-terminal region of the toxin is
      largely dispensable. Through genome mining we identified additional SLS-like
      clusters in diverse Firmicutes, Spirochaetes and Actinobacteria. Among the
      Spirochaete clusters, naturally truncated SLS-like precursors were found in the
      genomes of three Lyme disease-causing Borrelia burgdorferi sensu lato (Bbsl)
      strains. Although unable to restore hemolysis in SLS-deficient S. pyogenes, a
      Bbsl SLS-like precursor peptide was converted to a cytolysin using purified SLS
      biosynthetic enzymes. A PCR-based screen demonstrated that SLS-like clusters are
      substantially more prevalent in Bbsl than inferred from publicly available genome
      sequences. CONCLUSIONS: The mutagenesis data described herein indicate that the
      minimal cytolytic unit of SLS encompasses the NPH region of the core peptide.
      Interestingly, this region is found in all characterized TOMM cytolysins, as well
      as the novel putative TOMM cytolysins we discovered. We propose that this
      conserved region represents the defining feature of the SLS-like TOMM family. We
      demonstrate the cytolytic potential of a Bbsl SLS-like precursor peptide, which
      has a core region of similar length to the SLS minimal cytolytic unit, when
      modified with purified SLS biosynthetic enzymes. As such, we speculate that some
      Borrelia have the potential to produce a TOMM cytolysin, although the biological
      significance of this finding remains to be determined. In addition to providing
      new insight into the structure-activity relationships of SLS, this study greatly
      expands the cytolysin group of TOMMs.

PMID- 26204952
TI  - Spatio-temporal prevalence of porcine cysticercosis in Madagascar based on meat
      inspection.
AB  - BACKGROUND: Taenia solium cysticercosis is a parasitic meat-borne disease that is
      highly prevalent in pigs and humans in Africa, but the burden is vastly
      underestimated due to the lack of official control along the pork commodity
      chain, which hampers long-term control policies. METHODS: The apparent and
      corrected prevalences of T. solium cysticercosis were investigated in pork
      carcasses slaughtered and retailed in Antananarivo (Madagascar), thanks to a 12
      month monitoring plan in two urban abattoirs. RESULTS: Overall apparent
      prevalence was estimated at 4.6% [4.2 - 5.0%]. The corrected overall prevalence
      defined as the estimated prevalence after accounting for the sensitivity of meat
      inspection was 21.03% [19.18- 22.87%]. Significant differences among geoclimatic
      regions were observed only for indigenous pigs, with an apparent prevalence
      estimated at 7.9% [6.0 - 9.9%] in the northern and western regions, 7.3% [6.0 -
      8.6%] in the central region, and 6.2% [4.7 - 7.8%] in the southern region. In the
      central region, where both exotic and indigenous pigs were surveyed, indigenous
      pigs were 8.5 times [6.7 - 10.7] more likely to be infected than exotic improved
      pigs. Urban consumers were more likely to encounter cysticercosis in pork in the
      rainy season, which is a major at risk period, in particular in December.
      Differences between abattoirs were also identified. CONCLUSION: Our results
      underline the need for improved surveillance and control programmes to limit T.
      solium cysticercosis in carcasses by introducing a risk-based meat inspection
      procedure that accounts for the origin and breed of the pigs, and the season.

PMID- 26204953
TI  - Immune response to Propionibacterium acnes in patients with sarcoidosis--in vivo
      and in vitro.
AB  - BACKGROUND: Propionibacterium acnes was found in lungs and lymph nodes of
      patients with sarcoidosis and may induce hypersensitivity type granuloma
      formation. Data regarding the immune response to P. acnes of European sarcoid
      patients are scarce. METHODS: We assessed the total IgG and IgA amount and
      specific antibodies to P. acnes and to Staphylococcus aureus, serving as a
      control, in BAL fluid of 64 patients with sarcoidosis and of 21 healthy
      volunteers. In a subcohort of sarcoid patients and controls, TNF-alpha and GM-CSF
      production of BAL cells stimulated with heat-killed P. acnes were measured.
      RESULTS: In sarcoid patients, the total IgG and IgA levels in BAL fluid were
      significantly elevated compared to healthy volunteers. IgG and IgA titres against
      P. acnes and S. aureus were increased in sarcoid patients, yet based on the total
      amount of antibodies, only antibodies directed against P. acnes were relatively
      and significantly increased. Furthermore, BAL cells of sarcoid patients produced
      significantly more TNF-alpha and GM-CSF upon stimulation with heat-killed P.
      acnes compared to controls. CONCLUSIONS: Patients with sarcoidosis had elevated
      levels of specific antibodies against P. acnes which suggest contact with this
      bacterium in the past. Furthermore, BAL cells of sarcoid patients produced
      inflammatory cytokines (TNF-alpha and GM-CSF) upon stimulation with P. acnes
      indicating potential involvement of this pathogen in the pathogenesis of
      sarcoidosis in some patients.

PMID- 26204954
TI  - NRAS (Q61R), BRAF (V600E) immunohistochemistry: a concomitant tool for mutation
      screening in melanomas.
AB  - BACKGROUND: The determination of NRAS and BRAF mutation status is a major
      requirement in the treatment of patients with metastatic melanoma. Mutation
      specific antibodies against NRAS(Q61R) and BRAF(V600E) proteins could offer
      additional data on tumor heterogeneity. The specificity and sensitivity of
      NRAS(Q61R) immunohistochemistry have recently been reported excellent. We aimed
      to determine the utility of immunohistochemistry using SP174 anti-NRAS(Q61R) and
      VE1 anti-BRAF(V600E) antibodies in the theranostic mutation screening of
      melanomas. METHODS: 142 formalin-fixed paraffin-embedded melanoma samples from 79
      patients were analyzed using pyrosequencing and immunohistochemistry. RESULTS: 23
      and 26 patients were concluded to have a NRAS-mutated or a BRAF-mutated melanoma
      respectively. The 23 NRAS (Q61R) and 23 BRAF (V600E) -mutant samples with
      pyrosequencing were all positive in immunohistochemistry with SP174 antibody and
      VE1 antibody respectively, without any false negative. Proportions and
      intensities of staining were varied. Other NRAS (Q61L) , NRAS (Q61K) , BRAF
      (V600K) and BRAF (V600R) mutants were negative in immunohistochemistry. 6 single
      cases were immunostained but identified as wild-type using pyrosequencing (1 with
      SP174 and 5 with VE1). 4/38 patients with multiple samples presented molecular
      discordant data. Technical limitations are discussed to explain those
      discrepancies. Anyway we could not rule out real tumor heterogeneity.
      CONCLUSIONS: In our study, we showed that combining immunohistochemistry analysis
      targeting NRAS(Q61R) and BRAF(V600E) proteins with molecular analysis was a
      reliable theranostic tool to face challenging samples of melanoma.

PMID- 26204955
TI  - Comparative evaluation of three mixed dentition analyses and formulation of
      regression equations for north Indian population: A cross-sectional study.
AB  - BACKGROUND: The present study was undertaken to evaluate the accuracy of methods
      proposed by Tanaka and Johnston, Moyers, and Bernabe and Flores-Mir to forecast
      the mesiodistal dimensions of permanent canine and premolars in a North Indian
      population. METHODS: Mesiodistal tooth dimensions were measured from study models
      representing 68 male and 68 female subjects (aged 12-16 years) of North Indian
      descent. The mesiodistal dimensions of the teeth were measured using a digital
      Vernier caliper (providing measurements to 0.01 mm accuracy). The measurements of
      canine and premolars were summed up and compared with those derived from Tanaka
      and Johnston equations, Moyers probability tables (75 th percentile), and Bernabe
      and Flores-Mir equations. RESULTS: All the three methods exhibited overestimation
      of actual sum of permanent canine and premolars in both the arches and genders in
      this population. Because of the discrepancy observed, new regression analyses in
      the form of Y = A + B (X) were formulated similar to those proposed by Tanaka and
      Johnston originally, but separately for males and females. In males, the
      correlation coefficient between the sum of mesiodistal widths of mandibular
      incisors and the sum of widths of canine and premolars was 0.637 and 0.685 for
      maxilla and mandible, respectively. This value was 0.55 for maxilla and 0.64 for
      mandible in females. These values were found to be statistically significant.
      CONCLUSION: All the methods evaluated in the study were found to be inaccurate
      and they overestimate the mesiodistal widths of permanent canine and premolars in
      North Indian population. Revised linear regression equations were derived using
      the data obtained from this population.

PMID- 26204956
TI  - Longitudinal follow up of a boy affected by Pol III-related leukodystrophy: a
      detailed phenotype description.
AB  - BACKGROUND: The 4H syndrome (hypomyelination, hypodontia, hypogonadotropic
      hypogonadism) is a newly recognized leukodystrophy. The classical form is
      characterized by the association of hypomyelination, abnormal dentition, and
      hypogonadotropic hypogonadism, but the recent identification of two genes (POLR3A
      and POLR3B) responsible for the syndrome demonstrates that these three main
      characteristics can be variably combined among "Pol-III (polymerase III)-related
      leukodystrophies." CASE PRESENTATION: We report on the clinical,
      neuroradiological and endocrinological follow-up of a male affected by 4H
      syndrome with confirmed POLR3B mutations (c.1568 T > A/p.V523E variant in exon 15
      and the novel c.1988C > T/p.T663I mutation in exon 19). Spastic-ataxic gait with
      worsening of motor performance, progressive moderate intellectual disability and
      language difficulties were the main neurological findings observed. The first six
      years of substantial stability of the clinical and imaging features were followed
      by additional six years that showed a progressive worsening of motor, language
      and learning disabilities in relation to a progression of the cerebellar
      involvement. Hypogonadotropic hypogonadism and growth hormone deficiency followed
      by central hypocortisolism became part of the patient's phenotype. Thyroid
      function resulted unaffected during follow up. CONCLUSIONS: A novel mutation in
      POLR3B in a patient with an analogue phenotype than those previously described
      but with more extensive endocrinological features, including hypogonadotropic
      hypogonadism, growth hormone deficiency and hypocortisolism, was described. These
      findings permit to better define the clinical spectrum of the disease, to direct
      specific genetic tests and to tailor clinical management.

PMID- 26204957
TI  - Validation of the safety attitudes questionnaire (short form 2006) in Italian in
      hospitals in the northeast of Italy.
AB  - BACKGROUND: Studying safety attitudes of front-line workers can help hospital
      managers take initiatives to improve patient safety. The Safety Attitudes
      Questionnaire, a psychometric tool that measures safety attitudes in health
      facilities, has been used and validated in several languages worldwide but there
      is no Italian version available. Hence, the study is aimed at cross-culturally
      validating the questionnaire (short form 2006) in Italian at two hospitals in the
      Veneto region (northeastern Italy). METHODS: The translation and linguistic
      adaptation process of the questionnaire followed the World Health Organization
      guidelines. The questionnaire was delivered to staff working in four departments
      in two hospitals. Confirmatory factor analysis was used to assess the content
      validity of a pre-specified factor model that recognizes seven safety factors of
      the SAQ. Retest was performed to assess reliability. Internal consistency of
      items and safety factors was evaluated via Cronbach's alpha. RESULTS: Response
      rate was 60 % (n = 261/433). Test-retest correlation between items and factors
      showed a high degree of agreement. Goodness-of-fit indices demonstrated an
      acceptable hypothesis model with seven safety factors. Cronbach's alpha of a
      whole questionnaire was 0.85, demonstrating a good internal consistency.
      Polychoric correlations showed that the factors are well correlated with each
      other. Stress recognition was found to have negative correlation with other
      safety factors. CONCLUSIONS: The Safety Attitudes Questionnaire in Italian
      language has satisfactory psychometric characteristics and is a valid instrument
      to measure safety culture in Italian hospitals.

PMID- 26204958
TI  - Synthesis, relaxation properties and in vivo assessment of a carborane-GdDOTA
      monoamide conjugate as an MRI blood pool contrast agent.
AB  - The synthesis, relaxivity measurements and in vivo assessment of a carborane
      GdDOTA-monoamide (CB-GdDOTA-MA) amphiphilic conjugate as a blood pool contrast
      agent (BPCA) is reported. This BPCA exhibited excellent binding (87.4%) with
      human serum albumin (HSA) and showed a higher relaxivity value (r1 = 6.8 mM(-1)
      s(-1), 7 T) as compared to the clinically used BPCA, MS-325 (r1 = 5.1 mM(-1) s(
      1), 9.4 T) in PBS. The blood pool contrast enhancement (CE) capability of CB
      GdDOTA-MA was evaluated by performing MR angiography (MRA) in CF1 mice (n = 4) at
      a Gd dose of 0.1 mmol per kg body weight. The significant CE of blood vessels
      persisted for about 3-4 min post-injection (p.i.) and quickly diminishes over
      time. The significant CE of the bladder for up to 3 h p.i. indicated that the
      renal system is the primary clearance pathway for CB-GdDOTA-MA. However, the CE
      of liver tissues and intestine (up to 24 h p.i.) is suggestive of a significant
      hepatic uptake of the CB-GdDOTA-MA. 

PMID- 26204959
TI  - Co-electrolysis of steam and CO2 in full-ceramic symmetrical SOECs: a strategy
      for avoiding the use of hydrogen as a safe gas.
AB  - The use of cermets as fuel electrodes for solid oxide electrolysis cells requires
      permanent circulation of reducing gas, e.g. H2 or CO, so called safe gas, in
      order to avoid oxidation of the metallic phase. Replacing metallic based
      electrodes by pure oxides is therefore proposed as an advantage for the
      industrial application of solid oxide electrolyzers. In this work, full-ceramic
      symmetrical solid oxide electrolysis cells have been investigated for steam/CO2
      co-electrolysis. Electrolyte supported cells with
      La(0.75)Sr(0.25)Cr(0.5)Mn(0.5)O3-delta reversible electrodes have been fabricated
      and tested in co-electrolysis mode using different fuel compositions, from pure
      H2O to pure CO2, at temperatures between 850-900  degrees C. Electrochemical
      impedance spectroscopy and galvanostatic measurements have been carried out for
      the mechanistic understanding of the symmetrical cell performance. The content of
      H2 and CO in the product gas has been measured by in-line gas micro
      chromatography. The effect of employing H2 as a safe gas has also been
      investigated. Maximum density currents of 750 mA cm(-2) and 620 mA cm(-2) have
      been applied at 1.7 V for pure H2O and for H2O : CO2 ratios of 1 : 1,
      respectively. Remarkable results were obtained for hydrogen-free fuel
      compositions, which confirmed the interest of using ceramic oxides as a fuel
      electrode candidate to reduce or completely avoid the use of safe gas in
      operation minimizing the contribution of the reverse water shift reaction (RWSR)
      in the process. H2 : CO ratios close to two were obtained for hydrogen-free tests
      fulfilling the basic requirements for synthetic fuel production. An important
      increase in the operation voltage was detected under continuous operation leading
      to a dramatic failure by delaminating of the oxygen electrode.

PMID- 26204960
TI  - Tackling virological failure in HIV-infected children living in Africa.
AB  - Drug resistance in HIV-infected children is one of the main contributors to
      antiretroviral treatment (ART) failure, especially in developing countries. Sub
      Saharan Africa has the largest burden of pediatric HIV infection in the world.
      Herein, we systematically review the current status of ART failure in HIV
      infected African children. A literature search for publications within 10 years
      was performed through PubMed to identify relevant articles. Included studies
      examined the impact of timing of ART initiation, criteria for diagnosing
      therapeutic failure, predictors of therapeutic failure, management strategies and
      future directions to minimize failure rates in these pediatric populations.
      Although there is scale-up of ART programs in Africa, novel therapeutic and
      management strategies are needed to overcome current challenges. 

PMID- 26204961
TI  - Patterns of care for metastatic renal cell carcinoma in Australia.
AB  - OBJECTIVE: To examine the patterns of care and outcomes for metastatic renal cell
      carcinoma (mRCC) in Australia, where there are limited reimbursed treatment
      options. In particular, we aim to explore prescribing patterns for first-line
      systemic treatment, the practice of an initial watchful-waiting approach, and the
      use of systemic treatments in elderly patients. SUBJECTS/PATIENTS AND METHODS:
      Patients with mRCC undergoing treatment between 2006 and 2012 were identified
      from four academic hospitals in Victoria and Australian Capital Territory.
      Demographic, clinicopathological, treatment, and survival data were recorded by
      chart review. Descriptive statistics were used to report findings. Survival was
      estimated by the Kaplan-Meier method and compared using the log-rank test. The
      study was supported by a grant from Pfizer Australia. RESULTS: Our study
      identified 212 patients with mRCC for analysis. Patients were predominantly of
      clear cell histology (75%), Eastern Cooperative Oncology Group performance status
      <2 (67%) and with favourable/intermediate Memorial Sloan-Kettering Cancer Center
      risk (68%). The median age at diagnosis was 61 years. In all, 163 (77%) patients
      received first-line systemic therapy, while 49 (23%) received best supportive
      care (BSC). The most frequently used first-line treatment was sunitinib (125
      patients, 77%). Patients who received sunitinib had a median overall survival
      (OS) of 27.6 months. In all, 43% of patients who received sunitinib underwent a
      watchful-waiting period of >90 days before initiating treatment; these patients
      had a median OS of 56.3 months. Elderly patients (50 patients aged >=70 years)
      were more likely to receive BSC alone than younger patients (46% vs 16%, P <
      0.001). Of those who received systemic therapy, elderly patients were also more
      likely to have upfront dose reductions (30% vs 8%, P = 0.03). CONCLUSION: Our
      study of patients with mRCC treated in Australian centres showed that sunitinib
      was the most commonly prescribed systemic treatment between 2006 and 2012,
      associated with survival outcomes similar to pivotal studies. We also found that
      an initial watchful-waiting approach is commonly adopted without apparent
      detriment to survival. And finally, we found that age has an impact on the
      prescribing of systemic therapy.

PMID- 26204962
TI  - Association of polymorphisms in the MAFB gene and the risk of coronary artery
      disease and ischemic stroke: a case-control study.
AB  - BACKGROUND: The v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B
      gene (MAFB) has been associated with serum lipid levels in the Eurpean
      population, but little is known about such association in the Chinese population
      or in atherosclerosis-related patients. Therefore, the purpose of the present
      study was to assess the association of the single nucleotide polymorphisms (SNPs)
      in the MAFB and serum lipid levels and the risk of coronary artery disease (CAD)
      and ischemic stroke (IS) in the Chinese population. METHODS: A total of 1,065
      unrelated patients (CAD, 525 and IS, 540) and 539 healthy controls were recruited
      in this study. Genotypes of the MAFB rs2902940 and rs6102059 SNPs were determined
      by the Snapshot technology platform. RESULTS: The rs2902940AA genotype was
      associated with an increased risk of CAD (adjusted OR = 1.63, 95% CI = 1.07-2.48,
      P = 0.023) and IS (adjusted OR = 1.69, 95% CI = 1.09-2.61, P = 0.017). The
      rs2902940GA/AA genotypes were also associated with an increased risk of CAD
      (adjusted OR = 1.56, 95% CI = 1.04-2.32, P = 0.030 for GA/AA vs. GG) and IS
      (adjusted OR = 1.72, 95% CI = 1.14-2.60, P = 0.010 for GA/AA vs. GG). Significant
      interactions were observed only in those with higher body mass index (BMI),
      hypertension and diabetes (P < 0.05). The subjects with rs2902940GA/AA genotypes
      in controls had lower serum ApoAI levels than the subjects with GG genotype (P =
      0.024). CONCLUSIONS: The rs2902940A allele carriers in the MAFB conferred a
      decreased serum ApoAI level in controls and an increased risk of CAD and IS. The
      rs2902940GA/AA genotypes interacted with higher BMI, hypertension and diabetes to
      contribute the risk of CAD and IS.

PMID- 26204964
TI  - The blueberry sign.

PMID- 26204963
TI  - Periostin enhances adipose-derived stem cell adhesion, migration, and therapeutic
      efficiency in Apo E deficient mice with hind limb ischemia.
AB  - INTRODUCTION: Therapeutic angiogenesis by transplantation of
      autologous/allogeneic adipose-derived stem cells (ADSCs) is a potential approach
      for severe ischemic diseases. However, poor viability, adhesion, migration and
      differentiation limit the therapeutic efficiency after the cells were
      transplanted into the targeted area. Periostin, an extracellular matrix protein,
      exhibits a critical role in wound repair as well as promotes cell adhesion,
      survival, and angiogenesis. METHOD: ADSCs were obtained and genetically
      engineered with periostin gene (P-ADSCs). The viability, proliferation,
      migration, and apoptosis of P-ADSCs under hypoxia were analyzed. Moreover, P
      ADSCs were implanted into Apo E deficient mice with hind limb ischemia. The Laser
      Doppler perfusion index, immunofluorescence, and histological pathology assay
      were tested to evaluate the therapeutic effects. The associated molecular
      mechanism of periostin on the proliferation, adhesion, migration, and
      differentiation of ADSCs was also analyzed. RESULTS: The in vitro studies have
      shown that periostin-transfected ADSCs (P-ADSCs) promoted viability,
      proliferation, and migration of ADSCs. Apoptosis of ADSCs was inhibited under
      hypoxic conditions. The Laser Doppler perfusion index was significantly higher in
      the P-ADSCs group compared with that in the ADSC and control groups after 4
      weeks. Immunofluorescence and histological pathology assay showed that the P
      ADSCs were in and around the ischemic sites, and some cells differentiated into
      capillaries and endothelium. Microvessel densities were significantly improved in
      P-ADSCs group compared with those in the control group. The molecular mechanisms
      that provide the beneficial effects of periostin were connected with the
      upregulated expression of integrinbeta1/FAK/PI3K/Akt/eNOS signal pathway and the
      increased secretion of growth factors. CONCLUSION: Overexpression of periostin by
      gene transfection on ADSCs promotes survival, migration, and therapeutic
      efficiency, which will bring new insights into the treatment of critical limb
      ischemia.

PMID- 26204965
TI  - Defining Our Clinical Practice: The Identification of Genetic Counseling Outcomes
      Utilizing the Reciprocal Engagement Model.
AB  - The need for evidence-based medicine, including comparative effectiveness studies
      and patient-centered outcomes research, has become a major healthcare focus. To
      date, a comprehensive list of genetic counseling outcomes, as espoused by genetic
      counselors, has not been established and thus, identification of outcomes unique
      to genetic counseling services has become a priority for the National Society of
      Genetic Counselors (NSGC). The purpose of this study was to take a critical first
      step at identifying a more comprehensive list of genetic counseling outcomes.
      This paper describes the results of a focus group study using the Reciprocal
      Engagement Model (REM) as a framework to characterize patient-centered outcomes
      of genetic counseling clinical practice. Five focus groups were conducted with 27
      peer nominated participants who were clinical genetic counselors, genetic
      counseling program directors, and/or outcomes researchers in genetic counseling.
      Members of each focus group were asked to identify genetic counseling outcomes
      for four to five of the 17 goals of the REM. A theory-driven, thematic analysis
      of focus group data yielded 194 genetic counseling outcomes across the 17 goals.
      Participants noted some concerns about how genetic counseling outcomes will be
      measured and evaluated given varying stakeholders and the long-term nature of
      genetic concerns. The present results provide a list of outcomes for use in
      future genetic counseling outcomes research and for empirically-supported
      clinical interventions. 

PMID- 26204967
TI  - Indolealkylamines from Toad Vertebrates and Sea Invertebrates - Their
      Identification and Potential Activities on the Central Nervous System.
AB  - Indolealkylamines (IAAs) are biogenic amines and derivatives of 5
      hydroxytryptamine, acting primarily on serotonin receptors. IAAs are often
      considered the most thoroughly investigated group of aromatic amines in the
      amphibian skin. On the contrary, at present the detailed knowledge of these
      compounds in lower organisms is still limited and the biogenic amine receptors,
      mediating hormonal and modulatory functions, are largely unknown in primitive
      invertebrates. However, some active research is currently underway investigating
      this class of biogenic amines. Notably, during the last three decades several
      investigations have demonstrated the biological activity of endogenous biogenic
      amines in cnidarians, which are known to be the lowest beings equipped with an
      effective, even though rudimentary, nervous system. Toads, especially those from
      the Bufonidae family, constitute a significant part of the amphibian family and
      are an identified source of IAAs. To date fourteen IAAs have been identified in
      the skins of toad species. All are 5-substituted IAA derivatives acting mainly on
      the central nervous system (CNS), with most exhibiting some degrees of 5-HT2A
      receptor selectivity. This selective ability presents potential for their use in
      the development of treatments for various disorders such as schizophrenia,
      depression, anxiety, obsessive-compulsive disorders and chronic pain conditions.
      There are indications that some IAAs may also show subclass selectivity through
      binding to multiple 5-HT receptor subtypes. Thus, there exists an additional
      promising platform for the development of therapeutics targeting multiple 5-HT
      receptors. In this review, IAAs occurring naturally in various species of toad
      skins, which have been identified and isolated since 1944 are summarized and
      comparisons are made with similar biogenic amines recognized in cnidarians to
      date. Such comparisons highlight the potential to utilize existing knowledge
      gathered from vertebrates, such as toads in order to improve the understanding of
      the activities of such compounds in lower invertebrates.

PMID- 26204966
TI  - Ion Mobility Mass Spectrometry for Ion Recovery and Clean-Up of MS and MS/MS
      Spectra Obtained from Low Abundance Viral Samples.
AB  - Many samples of complex mixtures of N-glycans released from small amounts of
      material, such as glycoproteins from viruses, present problems for mass
      spectrometric analysis because of the presence of contaminating material that is
      difficult to remove by conventional methods without involving sample loss. This
      study describes the use of ion mobility for extraction of glycan profiles from
      such samples and for obtaining clean CID spectra when targeted m/z values capture
      additional ions from those of the target compound. N-glycans were released
      enzymatically from within SDS-PAGE gels, from the representative recombinant
      glycoprotein, gp120 of the human immunodeficiency virus, and examined by direct
      infusion electrospray in negative mode followed by ion mobility with a Waters
      Synapt G2 mass spectrometer (Waters MS-Technologies, Manchester, UK). Clean
      profiles of singly, doubly, and triply charged N-glycans were obtained from
      samples in cases where the raw electrospray spectra displayed only a few glycan
      ions as the result of low sample concentration or the presence of contamination.
      Ion mobility also enabled uncontaminated CID spectra to be obtained from glycans
      when their molecular ions displayed coincidence with ions from fragments or
      multiply charged ions with similar m/z values. This technique proved to be
      invaluable for removing extraneous ions from many CID spectra. The presence of
      such ions often produces spectra that are difficult to interpret. Most CID
      spectra, even those from abundant glycan constituents, benefited from such clean
      up, showing that the extra dimension provided by ion mobility was invaluable for
      studies of this type.

PMID- 26204968
TI  - Bio-transformation of Glycerol to 3-Hydroxypropionic Acid Using Resting Cells of
      Lactobacillus reuteri.
AB  - Lactobacillus reuteri grown in MRS broth containing 20 mM glycerol exhibits 3.7
      fold up-regulation of 3-hydroxypropionic acid (3-HP) pathway genes during the
      stationary phase. Concomitantly, the resting cells prepared from stationary phase
      show enhancement in bio-conversion of glycerol, and the maximum specific
      productivity (q p) is found to be 0.17 g 3-HP per g CDW per hour. The regulatory
      elements such as catabolite repression site in the up-stream of 3-HP pathway
      genes are presumed for the augmentation of glycerol bio-conversion selectively in
      stationary phase. However, in the repression mutant, the maximum q p of 3-HP
      persisted in the stationary phase-derived resting cells indicating the role of
      further regulatory features. In the production stage, the external 3-HP
      concentration of 35 mM inhibits 3-HP synthesis. In addition, it has also
      moderated 1,3-propanediol formation, as it is a redox bio-catalysis involving
      NAD(+)/NADH ratio of 6.5. Repeated batch bio-transformation has been used to
      overcome product inhibition, and the total yield (Ypx) of 3-HP from the
      stationary phase-derived biomass is 3.3 times higher than that from the non
      repeated mode. With the use of appropriate gene expression condition and repeated
      transfer of biomass, 3-HP produced in this study can be used for low-volume, high
      value applications.

PMID- 26204969
TI  - An analysis of marketing authorisation applications via the mutual recognition
      and decentralised procedures in Europe.
AB  - PURPOSE: The aim of this study is to provide a comprehensive overview of the
      outcomes of marketing authorisation applications via the mutual recognition and
      decentralised procedures (MRP/DCP) and assess determinants of licensing failure
      during CMDh referral procedures. METHODS: All MRP/DCP procedures to the Co
      ordination group for Mutual recognition and Decentralised procedures-human (CMDh)
      during the period from January 2006 to December 2013 were analysed. Reasons for
      starting referral procedures were scored. In addition, a survey under
      pharmaceutical companies was performed to estimate the frequency of licensing
      failure prior to CMDh referrals. RESULTS: During the study period, 10392 MRP/DCP
      procedures were finalized. Three hundred seventy-seven (3.6%) resulted in a
      referral procedure, of which 70 (19%) resulted in licensing failure, defined as
      refusal or withdrawal of the application. The frequency of CMDh referrals
      decreased from 14.5% in 2006 to 1.6% in 2013. Of all referrals, 272 (72%) were
      resolved through consensus within the CMDh, the remaining 105 (28%) were resolved
      at the level of the CHMP. Most referrals were started because of objections
      raised about the clinical development program. Study design issues and objections
      about the demonstration of equivalence were most likely to result in licensing
      failure. An estimated 11% of all MRP/DCP procedures resulted in licensing failure
      prior to CMDh referral. CONCLUSION: Whereas the absolute number of MRP/DCP
      procedures resulting in a referral has reduced substantially over the past years,
      no specific time trend could be observed regarding the frequency of referrals
      resulting in licensing failure. Increased knowledge at the level of companies and
      regulators has reduced the frequency of late-stage failure of marketing
      applications via the MRP/DCP.

PMID- 26204970
TI  - National cost savings from observation unit management of syncope.
AB  - OBJECTIVES: Syncope is a frequent emergency department (ED) presenting complaint
      and results in a disproportionate rate of hospitalization with variable
      management strategies. The objective was to estimate the annual national cost
      savings, reduction in inpatient hospitalizations, and reduction in hospital bed
      hours from implementation of protocolized care in an observation unit. METHODS:
      We created a Monte Carlo simulation by building a model that reflects current
      clinical practice in the United States and uses inputs gathered from the most
      recent available peer-reviewed literature and national survey data. ED visit
      volume was adjusted to reflect observation unit availability and the portion of
      observation visits requiring subsequent inpatient care. A recent multicenter
      randomized controlled study informed the cost savings and length of stay
      reduction per observation unit visit model inputs. The study population included
      patients aged 50 years and older with syncope deemed at intermediate risk for
      serious 30-day cardiovascular outcomes. RESULTS: The mean (+/-SD) annual cost
      savings was estimated to be $108 million (+/-$89 million) from avoiding 235,000
      (+/-13,900) inpatient admissions, resulting in 4,297,000 (+/-1,242,000) fewer
      hospital bed hours. CONCLUSIONS: The potential national cost savings for managing
      selected patients with syncope in a dedicated observation unit is substantial.
      Syncope is one of many conditions suitable for care in an observation unit as an
      alternative to an inpatient setting. As pressure to decrease hospital length of
      stay and bill short-stay hospitalizations as observation increases, syncope
      illustrates the value of observation unit care.

PMID- 26204971
TI  - Education and Imaging. Gastrointestinal: Important cause of mid-esophageal ulcer.

PMID- 26204972
TI  - The potential of L-shell X-ray fluorescence CT (XFCT) for molecular imaging.
AB  - X-ray fluorescence CT (XFCT), a novel modality proposed for high-sensitivity high
      resolution molecular imaging of probes labelled with a high atomic-number
      element, has been performed with high-energy K-shell X-rays. XFCT performed with
      low-energy L-shell X-rays could, in principle, result in an increase of XFCT
      imaging sensitivity; however, the significant L-shell X-ray attenuation limits
      its use for imaging of small objects. This commentary discusses the advantages
      and drawbacks of L-shell XFCT imaging. 

PMID- 26204973
TI  - Three-Dimensional Anorectal Manometry Findings in Primigravida.
AB  - BACKGROUND: Vaginal delivery is an identified risk factor for anal sphincter
      injury. Therefore, to identify postpartum injury, an antepartum value or a normal
      range is required. However, at present, the normal values of 3D manometry are not
      available for primigravida or pregnant mothers. AIMS: Our study aims at
      describing normal values of 3D manometry in primigravida. METHODS: We analyzed
      3DARM data of 101 consecutive primigravid mothers in the third trimester. 3DARM
      was performed using the Given Imaging((r)) ManoScan system. RESULTS: The mean age
      was 24.7 (SD 5.1) years. All patients had a normal Cleveland Clinic Incontinence
      Score. The mean resting pressure (RP) was 87.02 (SD 18.43) mmHg and the maximum
      squeeze pressure (SP) was 179.21 (SD 52.96) mmHg. The mean length of the high
      pressure zone (HPZ) was 3.67 (SD 0.52) cm. Mean volumes for initial rectal
      sensation, urge, and discomfort were 50.36 (+/- 25.57), 76.70 (+/- 35.17), and
      143.40 (+/- 66.26) ml, respectively. The pressure asymmetry was highest in the
      lower anal sphincter and lowest in the mid-sphincter. There was a statistically
      significant relationship between the HPZ and RP (Pearson rho -0.23, p = 0.01),
      height (Pearson rho 0.22, p = 0.028), and weight (Pearson rho 0.25, p = 0.012).
      There were no statistically significant correlations between age, height, or
      weight with RP, SP, or balloon fill volumes. The characteristic appearance of the
      normal RP and SP was clearly visualized in all patients. CONCLUSIONS: Normal
      3DARM values for Sri Lankan primigravid mothers have been established. These may
      be used as reference values by other investigators.

PMID- 26204974
TI  - Readability of Healthcare Literature for Hepatitis B and C.
AB  - BACKGROUND: Patients increasingly use the Internet for educational material
      concerning health and diseases. This information can be utilized to teach the
      population of hepatitis B and C if properly written at the necessary grade level
      of the intended patient population. AIM: We explored the readability of online
      resources concerning hepatitis B and C. METHODS: Google searches were performed
      for "Hepatitis B" and "Hepatitis C." The Internet resources that were intended
      for patient education were used with specific exclusions. Articles were taken
      from 19 and 23 different websites focusing on the symptoms, diagnosis, and
      treatment of hepatitis B and C, respectively. The articles were analyzed using
      Readability Studio Professional Edition (Oleander Solutions, Vandalia, OH) using
      10 different readability scales. The results were compared and averaged to
      identify the anticipated academic grade level required to understand the
      information. RESULTS: The average readability scores of the 10 scales had ranges
      of 9.7-16.4 for hepatitis B and 9.2-16.4 for hepatitis C. The average academic
      reading grade level for hepatitis B was 12.6 +/- 2.1 and for hepatitis C was 12.7
      +/- 2.1. There was no significant discrepancy between the hepatitis B and C
      Internet resource averaged grade levels. CONCLUSION: The resources accessed by
      patients are higher than the previously determined necessary grade level for
      patients to properly understand the intended information. The American Medical
      Association recommends material should be simplified to grade levels below the
      sixth grade level to benefit the ideal proportion of the patient population.

PMID- 26204975
TI  - Gastrointestinal Bleeding Following Left Ventricular Assist Device (LVAD)
      Implantation: Taking the Pulse of the Problem.

PMID- 26204976
TI  - Effect of Ethanol Exposure on Slow Wave Activity and Smooth Muscle Contraction in
      the Rat Small Intestine.
AB  - BACKGROUND: Ethanol ingestion causes a variety of gastrointestinal disturbances
      including motility alterations. Slow wave propagation coordinates
      gastrointestinal motility, and abnormal slow wave activity is thought to
      contribute to motility disorders. To date, however, little is known about the
      effect of acute ethanol on motility disturbances associated with slow wave
      activity. AIM: To investigate the effect of ethanol on small intestine slow wave
      activity. METHODS: Segments (3-5 cm long) were isolated from the rat duodenum,
      jejunum, and ileum and mounted in an organ bath superfused with a normal Tyrode
      solution or with 1, 3, or 5% ethanol containing Tyrode. The electrical activities
      were recorded using an array of 121 extracellular electrodes, and motility
      recordings were performed using a digital video camera. RESULTS: The frequency
      and amplitude of slow wave activity were not altered at 1, 3, or 5% ethanol
      concentrations, but a significant drop in velocity was found at 3 and 5% ethanol.
      Furthermore, inexcitable areas appeared in a dose-dependent manner. Slow wave was
      sometimes also seen to propagate in a circular fashion, thereby describing a
      reentrant loop. Finally, in all duodenal, jejunal, and ileal segments, ethanol
      inhibited contractions and became fully quiescent at 3-5%. CONCLUSIONS: These
      studies for the first time demonstrate that ethanol significantly inhibits slow
      wave and spike activity in a dose-dependent manner and could also initiate
      reentrant activities. Intestinal contractions were also inhibited in a dose
      dependent manner. In conclusion, ethanol inhibits both slow wave activity and
      motor activity to cause ethanol-induced intestinal disturbances.

PMID- 26204977
TI  - Are There Any Etiology-Based Specific Findings of Imaging Appearance in Acute
      Liver Failure?

PMID- 26204978
TI  - Editorial: Old Problems and New Solutions in Pediatric Pulmonology.

PMID- 26204979
TI  - A Demyelinating Disease; What Lies Beneath?

PMID- 26204980
TI  - The effects of the Frag-Loc((r)) compression screw on distal radius fracture with
      a displaced dorsoulnar fragment.
AB  - PURPOSE: The purpose of this study is to evaluate the radiographic and clinical
      outcomes of the Frag-Loc((r)) compression screw with palmar plate fixation on
      distal radius fractures that include a displaced dorsoulnar fragment. PATIENTS
      AND METHODS: This retrospective comparative study enrolled 48 patients who had an
      unstable distal radius fracture and a dorsoulnar fragment that was more than 2 mm
      displaced and that had involvement of more than one-quarter of the articular
      surface. Twenty-six of the 48 patients were treated with a palmar locking plate
      without a Frag-Loc((r)) compression screw (group 1) and the other 22 patients
      were treated with palmar locking plate with a Frag-Loc((r)) compression screw to
      fix the dorsoulnar fragment (group 2). First, we reviewed all pre-surgical
      computerized tomographic (CT) scans. Second, we used the gap distance between the
      dorsoulnar and palmar fragment as seen on post-surgical axial and sagittal CT
      scans to determine outcome. The gap distance was measured at the point of maximum
      distance perpendicular to the plane of the main fracture line. Clinical outcomes
      were evaluated based on the patient-rated wrist evaluation (PRWE) score; the
      disabilities of the arm, shoulder and hand score; wrist active range of motion;
      and grip strength. RESULTS: There were no statistically significant differences
      in clinical outcome between the two groups. However, there were statistically
      significant differences in post-surgical gap distance. The mean post-surgical gap
      distances for group 1 were 1.3 mm (range 0.2-3.8 mm) on axial CT scans and 1.4 mm
      (range 0.5-2.4 mm) on sagittal CT scans, while the mean post-surgical gap
      distances for group 2 were 0.7 mm (range 0.7-1.6 mm) and 0.7 mm (range 0.3-1.1
      mm). CONCLUSION: This study shows that the Frag-Loc((r)) compression screw can
      reduce the gap distance between the dorsoulnar fragment and the distal radius,
      according to evaluation of post-surgical axial and sagittal CT scans. This result
      suggests that the Frag-Loc((r)) compression screw is an effective and simple
      treatment option to immobilize a dorsoulnar fragment associated with distal
      radius fracture.

PMID- 26204981
TI  - Interference screw for fixation of FDL transfer in the treatment of adult
      acquired flat foot deformity stage II.
AB  - INTRODUCTION: Flexor digitorum longus transfer and medial displacement calcaneal
      osteotomy have shown favourable results in the treatment of adult acquired flat
      foot deformity stage 2. Little is known about the resorbable interference screw
      for tendon fixation and postoperative patient satisfaction though. Moreover
      possible changes of radiographic parameters at final follow-up, possible implant
      associated complications and differences concerning clinical results at final
      follow-up to other studies using bone tunnel techniques for fixation of the FDL
      tendon were investigated. MATERIALS AND METHODS: 21 feet in 21 patients with a
      mean age of 51 years were evaluated pre- and postoperatively after a standardised
      operative procedure using MDCO and FDL transfer with interference screw fixation.
      Patients were evaluated with the American Orthopaedic Foot and Ankle Society
      Hindfoot Score and the Visual Analogue Scale at an average follow-up of 20
      months. Hindfoot radiographic parameters were evaluated according to AOFAS
      guidelines. For statistical analysis SPSS v.15.0.1 was used. RESULTS: The average
      AOFAS Score (from 42 to 95 points) and VAS (from 0.5 to 8 points) both increased
      significantly (p < 0.001 each) from preoperative to final follow-up as well as
      the hindfoot valgus (from 10 to 4 degrees (p = 0.005)) and the lateral talo-first
      metatarsal angle (from 13.6 preoperative to 5.2 degrees  at follow-up). 88
      percent of patients evaluated the postoperative result with "very good" or
      "good". Implant-associated complications could not be detected. CONCLUSION: We
      conclude that interference screw fixation for FDL transfer is a safe and
      promising operative technique, allowing a smaller skin incision without
      disrupting the normal interconnections at the knot of Henry, while achieving very
      high patient satisfaction and improving postoperative function as well as
      relieving pain. This method is technically easy to perform, has a low
      complication risk and we, therefore, recommend this fixation technique in
      patients with adult acquired flatfoot deformity stage 2.

PMID- 26204982
TI  - On the interaction of Helicobacter pylori NikR, a Ni(II)-responsive transcription
      factor, with the urease operator: in solution and in silico studies.
AB  - Helicobacter pylori (Hp) is a carcinogen that relies on Ni(II) to survive in the
      extreme pH conditions of the human guts. The regulation of genes coding for
      Ni(II) enzymes and proteins is effected by the nickel-responsive transcription
      factor NikR, composed of a DNA-binding domain (DBD) and a metal-binding domain
      (MBD). The scope of this study is to obtain the molecular details of the HpNikR
      interaction with the urease operator OP ureA , in solution. The size of the full
      length protein prevents the characterization of the HpNikR-OP ureA interaction
      using NMR. We thus investigated the two separate domains of HpNikR. The
      conservation of their oligomeric state was established by multiple-angle light
      scattering. Isothermal calorimetric titrations indicated that the thermodynamics
      of Ni(II) binding to the isolated MBD is independent of the presence of the
      adjacent DBDs. The NMR spectra of the isolated DBD support considerable
      conservation of its structural properties. The spectral perturbations induced on
      the DBD by OP ureA provided information useful to calculate a structural model of
      the HpNikR-OP ureA complex using a docking computational protocol. The NMR
      assignment of the residues involved in the protein-DNA interaction represents a
      starting point for the development of drugs potentially able to eradicate H.
      pylori infections. All evidences so far collected, in this and previous studies,
      consistently indicate that binding of Ni(II) to the MBD increases the HpNikR-DNA
      affinity by modulating the dynamic, and not the structural, properties of the
      protein, suggesting that the formation of a stable complex relies upon an induced
      fit mechanism. 

PMID- 26204983
TI  - Fluorescence switching of sanguinarine in micellar environments.
AB  - Sanguinarine (SANG), a key member of the benzylisoquinoline alkaloid family, is
      well-known for its various therapeutic applications such as antimicrobial,
      antitumor, anticancer, antifungal and anti-inflammatory etc. Depending on the
      medium pH, SANG exists in the iminium or alkanolamine form, which emits at 580 nm
      and 420 nm, respectively. Nucleophilic attack on the C6 carbon atom converts the
      iminium form to the alkanolamine form of SANG, and these two forms are equally
      important for the medicinal activities of SANG. To improve its potency as a drug,
      it is essential to get a physical insight into this conversion process. In this
      study, we have deployed steady sate and time-resolved spectroscopic techniques to
      probe this conversion process inside different micellar environments. We have
      observed that the conversion from the iminium to alkanolamine form takes place in
      neutral OBG (octyl-beta-d-glucopyranoside) and positively charged CTAB micelles,
      whereas the iminium form exclusively exists in negatively charged SDS micelles.
      This conversion from the iminium to alkanolamine form in the case of OBG and CTAB
      micelles may be attributed to the reduced pKa of this conversion process owing to
      the enhanced hydrophobicity experienced by the iminium form in between the
      surfactant head groups. On the other hand, the electrostatic attraction between
      positively charged iminium and negatively charged surfactant head groups
      stabilizes the iminium form in the stern layer of the SDS micelle. We believe
      that our observations are useful for selective transportation of any particular
      form of the drug into the active site. Moreover, loading of any particular form
      of drug can be easily monitored with the help of fluorescence color switch from
      orange (iminium) to violet (alkanolamine) without pursuing any sophisticated or
      complex technique. 

PMID- 26204984
TI  - Emergence of babesiosis in China-Myanmar border areas.
AB  - E. Vannier and P. J. Krause presented an excellent article on "Babesiosis in
      China, an emerging threat" in the Lancet Infectious Diseases in December 2014,
      which updated research on human babesiosis in China. However, a neglected and
      emerging issue has not been mentioned in EV & PJK's article, that is the co
      infections with B. microti and P. falciparum parasites that exist in syndemic
      areas, spatially in the China-Myanmar border areas of Yunnan province, China.
      Therefore, two important issues are addressed in here, including (i) the new
      emerging infections with Babesia spp. which are normally ignored in malaria
      endemic areas due to similarities in pathogenic morphology and clinical symptoms,
      (ii) additional consideration on babesiosis rather than drug-resistant malaria
      when anti-malaria treatment for the febrile cases in clinics fails. 

PMID- 26204985
TI  - Characterization of invasive Neisseria meningitidis strains from Quebec, Canada,
      during a period of increased serogroup B disease, 2009-2013: phenotyping and
      genotyping with special emphasis on the non-carbohydrate protein vaccine targets.
AB  - BACKGROUND: The epidemiology of invasive meningococcal disease (IMD) in Quebec,
      Canada, has been dominated in the past decade by a clone of serogroup B (MenB)
      Neisseria meningitidis defined by multi-locus sequence typing (MLST) as sequence
      type (ST)-269. With the licensure of a new MenB vaccine Bexsero (4CMenB) in
      Canada, this study characterized invasive N. meningitidis recovered in Quebec
      from 2009 to 2013, with an objective to examine the diversity of the 4CMenB
      vaccine antigens. Isolates were serogrouped by antisera and genogrouped by PCR,
      and further typed by whole cell ELISA for serotype and serosubtype antigens.
      Clonal analysis was done by MLST. Isolates were genotyped by analysis of their
      4CMenB vaccine antigen genes of PorA, factor H binding protein (fHbp), Neisserial
      Heparin Binding Antigen (NHBA), and Neisseria Adhesin A (NadA). RESULTS: Of the
      263 IMD isolates analysed, 229, 16, 10, 7, and 1 belonged to MenB, MenY, MenW,
      MenC, and MenX, respectively. Of the 229 MenB, 159 (69.4 %) were typed as ST-269
      clonal complex (CC); and they possessed a restricted number of three fHbp and
      five nhba gene alleles. Nine N. meningitidis isolates (eight MenB and one MenY)
      were found to possess at least one gene that encoded for an antigen that matched
      exactly with protein variants in the 4CMenB vaccine. Two MenB expressed PorA
      antigen P1.4 and possessed the nhba gene for peptide 2; four other MenB were
      predicted to have NHBA peptide 2; another two MenB were predicted to encode fHbp
      peptide 1.1; and a single MenY was found to have nadA gene for NadA peptide 8. In
      addition, another 172 isolates were found to possess genes for variant 1 fHbp
      peptides other than peptide 1.1 or NadA variant 1-2/3 peptides other than peptide
      8; and therefore, may potentially be covered by 4CMenB. CONCLUSION: The most
      prevalent clone of N. meningitidis in Quebec was ST-269 CC; and 96 % of the
      isolates in this CC were predicted to be covered by 4CMenB vaccine. Extensive
      genetic diversity was found in the other IMD isolates in Quebec which might
      suggest a lower coverage by the vaccine when compared to the ST-269 MenB.

PMID- 26204986
TI  - The first case report of a patient with simultaneous haemophilia A and
      accelerated phase chronic myelogenous leukaemia.

PMID- 26204987
TI  - Baseline Predictors of High Adherence to a Coitally Dependent Microbicide Gel
      Based on an Objective Marker of Use: Findings from the Carraguard Phase 3 Trial.
AB  - A randomized, placebo-controlled, efficacy trial of Carraguard was unable to
      demonstrate a reduction in women's risk of HIV infection, which may have been
      due, in part, to low adherence (gel used in 42 % of vaginal sex acts, on
      average). A secondary analysis was undertaken to understand baseline factors
      associated with high adherence (gel used in >=85 % of sex acts). Women who
      reported >=1 vaginal sex act, returned >=1 opened applicator, and had >=1
      conclusive post-enrollment HIV test (N = 5990) were included. Adherence was
      estimated as the ratio of average weekly applicator insertions (based on a dye
      stain assay indicating vaginal insertion)/average weekly sex acts (by self
      report). Multivariate logistic regression modeling indicated that coital
      frequency, site, contraception, and partner age difference had a significant
      impact on adherence. Women reporting >1 and <=2 vaginal sex acts per week, on
      average, were half as likely to be adherent as those reporting 1 vaginal sex act
      per week or less [adjusted odds ratio (AOR): 0.48; 95 % CI 0.38-0.61]; women from
      the Western Cape had one-third the odds of being adherent compared to women from
      KZN (AOR: 0.31; 95 % CI 0.23-0.41); compared to women using injectable
      contraception, women using any other or no method were more likely to be adherent
      (AOR: 1.30; 95 % CI 1.04-1.63); and women who had a larger age gap from their
      partners were more likely to be adherent (AOR: 1.03; 95 % CI 1.01-1.05; p =
      0.001). Despite low adherence, overall, 13 % of participants achieved nearly
      perfect adherence, indicating a potential niche for a coitally dependent
      microbicide. More research is needed on the impact of sexual patterns and HIV
      risk perception on product acceptability and adherence to improve counseling in
      ongoing trials and when products are eventually introduced.

PMID- 26204988
TI  - Lower incidence of chemosis with the Berke incision approach versus the swinging
      eyelid approach after deep lateral orbital wall decompression.
AB  - PURPOSE: To compare the incidence of chemosis following deep lateral orbital wall
      decompression using the Berke incision approach vs the swinging eyelid approach.
      METHODS: This study retrospectively reviewed 49 sides in 29 patients who
      underwent decompression via the Berke incision approach (Group A) and 122 sides
      in 71 patients who underwent decompression via the swinging eyelid approach
      (Group B). RESULTS: The incidence of chemosis was significantly lower in Group A
      (30.6%) compared with Group B (48.4%; p = 0.034). Although the period until
      subsidence of chemosis did not differ between the groups (p = 0.164), the ratio
      of sides that needed intensive postoperative care was lower in Group A than in
      Group B (p = 0.002). Chemosis tended to occur more frequently in sides with a
      history of steroid administration relative to those without previous steroid
      administration (Group A, p = 0.042; Group B, p = 0.059), although past radiation
      therapy and past combined radiation and steroid therapy did not influence the
      occurrence of chemosis (p > 0.050). Postoperative proptosis reduction was similar
      in both groups (p = 0.087). CONCLUSION: It was found that the Berke incision
      approach yielded a lower incidence of chemosis while achieving similar
      postoperative proptosis reduction in comparison with the swinging eyelid
      approach. These findings suggest that the Berke incision approach is an
      acceptable alternative procedure for deep lateral orbital wall decompression.

PMID- 26204989
TI  - Can serial changes of diastolic dysfunction signal incremental risk of
      chemotherapy-induced heart failure missed by the timing of declining LV ejection
      fraction?

PMID- 26204991
TI  - The good, bad, and ugly of incidental findings on cardiovascular-computed
      tomography.

PMID- 26204990
TI  - 2014 ACC/AHA Key Data Elements and Definitions for Cardiovascular Endpoint Events
      in Clinical Trials: A Report of the American College of Cardiology/American Heart
      Association Task Force on Clinical Data Standards (Writing Committee to Develop
      Cardiovascular Endpoints Data Standards).

PMID- 26204992
TI  - Modeling spread of KPC-producing bacteria in long-term acute care hospitals in
      the Chicago region, USA.
AB  - OBJECTIVE: Prevalence of bla KPC-encoding Enterobacteriaceae (KPC) in Chicago
      long-term acute care hospitals (LTACHs) rose rapidly after the first recognition
      in 2007. We studied the epidemiology and transmission capacity of KPC in LTACHs
      and the effect of patient cohorting. METHODS: Data were available from 4 Chicago
      LTACHs from June 2012 to June 2013 during a period of bundled interventions.
      These consisted of screening for KPC rectal carriage, daily chlorhexidine
      bathing, medical staff education, and 3 cohort strategies: a pure cohort (all KPC
      positive patients on 1 floor), single rooms for KPC-positive patients, and a
      mixed cohort (all KPC-positive patients on 1 floor, supplemented with KPC
      negative patients). A data-augmented Markov chain Monte Carlo (MCMC) method was
      used to model the transmission process. RESULTS: Average prevalence of KPC
      colonization was 29.3%. On admission, 18% of patients were colonized; the
      sensitivity of the screening process was 81%. The per admission reproduction
      number was 0.40. The number of acquisitions per 1,000 patient days was lowest in
      LTACHs with a pure cohort ward or single rooms for colonized patients compared
      with mixed-cohort wards, but 95% credible intervals overlapped. CONCLUSIONS:
      Prevalence of KPC in LTACHs is high, primarily due to high admission prevalence
      and the resultant impact of high colonization pressure on cross transmission. In
      this setting, with an intervention in place, patient-to-patient transmission is
      insufficient to maintain endemicity. Inclusion of a pure cohort or single rooms
      for KPC-positive patients in an intervention bundle seemed to limit transmission
      compared to use of a mixed cohort.

PMID- 26204993
TI  - A pre-screening FISH-based method to detect CRISPR/Cas9 off-targets in mouse
      embryonic stem cells.
AB  - The clustered regularly interspaced short palindromic repeat (CRISPR)/associated
      9 (Cas9) technology has been recently added to the tools allowing efficient and
      easy DNA targeting, representing a very promising approach to gene engineering.
      Using the CRISPR/Cas9 system we have driven the integration of exogenous DNA
      sequences to the X-linked Hprt gene of mouse embryonic stem cells. We show here
      that a simple fluorescence in situ hybridization (FISH)-based strategy allows the
      detection and the frequency evaluation of non-specific integrations of a given
      plasmid. FISH analysis revealed that these integrations do not match the software
      predicted off-target loci. We conclude that the frequency of these CRISPR
      mediated off-target DNA cuts is negligible, since, due to the occurrence of
      spontaneous double-strand breaks, we observed more aspecific plasmid integrations
      than those corresponding to predicted off-target sites. 

PMID- 26204994
TI  - Light therapy for better mood and insulin sensitivity in patients with major
      depression and type 2 diabetes: a randomised, double-blind, parallel-arm trial.
AB  - BACKGROUND: Major depression and type 2 diabetes often co-occur. Novel treatment
      strategies for depression in type 2 diabetes patients are warranted, as
      depression in type 2 diabetes patients is associated with poor prognosis and
      treatment results. Major depression and concurrent sleep disorders have been
      related to disturbances of the biological clock. The biological clock is also
      involved in regulation of glucose metabolism by modulating peripheral insulin
      sensitivity. Light therapy has been shown to be an effective antidepressant that
      'resets' the biological clock. We here describe the protocol of a study that
      evaluates the hypothesis that light therapy improves mood as well as insulin
      sensitivity in patients with a major depressive episode and type 2 diabetes.
      METHODS/DESIGN: This study is a randomised, double-blind, parallel-arm trial in
      98 participants with type 2 diabetes and a major depressive episode, according to
      DSM-IV criteria. We will assess whether light therapy improves depressive
      symptoms and insulin sensitivity, our primary outcome measures, and additionally
      investigate whether these effects are mediated by restoration of the circadian
      rhythmicity, as measured by sleep and hypothalamic-pituitary-adrenal axis
      activity. Participants will be randomly allocated to a bright white-yellowish
      light condition or dim green light condition. Participants will undergo light
      therapy for half an hour every morning for 4 weeks at home. At several time
      points, namely before the start of light therapy, during light therapy, after
      completion of 4 weeks of light therapy and after 4 weeks follow-up, several
      psychometrical, psychophysiological and glucometabolic measures will be
      performed. DISCUSSION: If light therapy effectively improves mood and insulin
      sensitivity in type 2 diabetes patients with a major depressive episode, light
      therapy may be a valuable patient friendly addition to the currently available
      treatment strategies. Additionally, if our data support the role of restoration
      of circadian rhythmicity, such an observation may guide further development of
      chronobiological treatment strategies in this patient population. TRIAL
      REGISTRATION: The Netherlands Trial Register (NTR) NTR4942 . Registered 13
      January 2015.

PMID- 26204995
TI  - Whole exome sequencing in extended families with autism spectrum disorder
      implicates four candidate genes.
AB  - Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders,
      characterized by impairment in communication and social interactions, and by
      repetitive behaviors. ASDs are highly heritable, and estimates of the number of
      risk loci range from hundreds to >1000. We considered 7 extended families (size
      12-47 individuals), each with >=3 individuals affected by ASD. All individuals
      were genotyped with dense SNP panels. A small subset of each family was typed
      with whole exome sequence (WES). We used a 3-step approach for variant
      identification. First, we used family-specific parametric linkage analysis of the
      SNP data to identify regions of interest. Second, we filtered variants in these
      regions based on frequency and function, obtaining exactly 200 candidates. Third,
      we compared two approaches to narrowing this list further. We used information
      from the SNP data to impute exome variant dosages into those without WES. We
      regressed affected status on variant allele dosage, using pedigree-based kinship
      matrices to account for relationships. The p value for the test of the null
      hypothesis that variant allele dosage is unrelated to phenotype was used to
      indicate strength of evidence supporting the variant. A cutoff of p = 0.05 gave
      28 variants. As an alternative third filter, we required Mendelian inheritance in
      those with WES, resulting in 70 variants. The imputation- and association-based
      approach was effective. We identified four strong candidate genes for ASD (SEZ6L,
      HISPPD1, FEZF1, SAMD11), all of which have been previously implicated in other
      studies, or have a strong biological argument for their relevance.

PMID- 26204996
TI  - Selectively Sized Graphene-Based Nanopores for in Situ Single Molecule Sensing.
AB  - The use of nanopore biosensors is set to be extremely important in developing
      precise single molecule detectors and providing highly sensitive advanced
      analysis of biological molecules. The precise tailoring of nanopore size is a
      significant step toward achieving this, as it would allow for a nanopore to be
      tuned to a corresponding analyte. The work presented here details a methodology
      for selectively opening nanopores in real-time. The tunable nanopores on a quartz
      nanopipette platform are fabricated using the electroetching of a graphene-based
      membrane constructed from individual graphene nanoflakes (o ~30 nm). The device
      design allows for in situ opening of the graphene membrane, from fully closed to
      fully opened (o ~25 nm), a feature that has yet to be reported in the literature.
      The translocation of DNA is studied as the pore size is varied, allowing for
      subfeatures of DNA to be detected with slower DNA translocations at smaller pore
      sizes, and the ability to observe trends as the pore is opened. This approach
      opens the door to creating a device that can be target to detect specific
      analytes. 

PMID- 26204997
TI  - Prevalent fragility fractures as risk factor for skeletal muscle function deficit
      and dysmobility syndrome in post-menopausal women.
AB  - BACKGROUND: Fragility fractures are a major burden for health and social care in
      elderly people. In order to identify earlier the "frail elders", new concepts of
      "dysmobility syndrome" and skeletal muscle function deficit (SMFD), including
      sarcopenia, osteoporosis, obesity, and mobility limitation, leading to a higher
      risk of fractures, have been recently introduced. There are very few studies
      investigating the association between fragility fractures and both the
      dysmobility syndrome and the SMFD. AIMS: The objective of our study is to
      investigate the role of previous fragility fractures as a risk factor in
      determining the dysmobility syndrome and/or the SMFD in post-menopausal women.
      METHODS: In this case-control study, we retrospectively examined data from the
      medical records of post-menopausal women aged 50 or older. We divided the study
      population in two groups. The first group includes women with a previous
      fragility fracture (cases) and the other group includes women without any
      previous osteoporotic fracture (controls). We identified the subjects with
      "dysmobility syndrome", "dynapenic SMFD", "sarcopenic SMFD", and "mixed SMFD" in
      both groups. Data collected refer to a 6-month period. RESULTS: We retrieved data
      of 121 post-menopausal women, 77 (63.64%) had already sustained a fragility
      fracture at any site (cases). The risk for dysmobility syndrome was significantly
      higher (adjusted OR for age and serum 25-OH vitamin D3 of 2.46) in the cases
      compared with the controls. DISCUSSION AND CONCLUSIONS: An early diagnosis of
      conditions limiting mobility, including dysmobility syndrome, might be useful to
      identify, among patients with osteoporotic fractures, those who might have a
      higher risk of a new fragility fracture.

PMID- 26204998
TI  - Water-Soluble Silicon Quantum Dots with Quasi-Blue Emission.
AB  - In this study, water-soluble silicon quantum dots have quasi-blue emission at 390
      nm by being capped with 1-vinylimidazole in resese micelles. As-obtained silicon
      quantum dots have a diameter of 2~5 nm and high crystallinity. The quasi-blue
      emission of the silicon quantum dots is likely attributed to the polarity of the
      capping ligands. Moreover, the silicon quantum dots are water-soluble and have
      photoluminescence nanosecond decay time, suggesting their potential application
      in biological field. 

PMID- 26204999
TI  - Unusual fast secondary relaxation in metallic glass.
AB  - The relaxation spectrum of glassy solids has long been used to probe their
      dynamic structural features and the fundamental deformation mechanisms.
      Structurally complicated glasses, such as molecular glasses, often exhibit
      multiple relaxation processes. By comparison, metallic glasses have a simple
      atomic structure with dense atomic packing, and their relaxation spectra were
      commonly found to be simpler than those of molecular glasses. Here we show the
      compelling evidence obtained across a wide range of temperatures and frequencies
      from a La-based metallic glass, which clearly shows two peaks of secondary
      relaxations (fast versus slow) in addition to the primary relaxation peak. The
      discovery of the unusual fast secondary relaxation unveils the complicated
      relaxation dynamics in metallic glasses and, more importantly, provides us the
      clues which help decode the structural features serving as the 'trigger' of
      inelasticity on mechanical agitations. 

PMID- 26205000
TI  - Predictors of response and drug survival in ankylosing spondylitis patients
      treated with infliximab.
AB  - BACKGROUND: The advent of anti-tumor necrosis factor-alpha (TNFalpha) drugs has
      changed the course of ankylosing spondylitis (AS). While data are available
      concerning the long term effectiveness of single anti-TNF agents, little has been
      published about predictors of treatment response in AS. The aim of this
      retrospective study was to evaluate the survival, effectiveness, and safety of
      infliximab over a 5-year period and to identify predictors of disease outcome.
      METHODS: Seventy AS patients attending the Rheumatology Clinic of the University
      of Padua who were treated with intravenous infliximab at 0, 2, 4 weeks and then
      every 6, 8, or up to 16 weeks were studied retrospectively. Demographic
      information, laboratory inflammatory and disease indices (BASDAI, BASFI, BASMI)
      were collected (at baseline, 3, 6, 12 months and once a year thereafter).
      Clinical improvement, drug tolerability, adverse events/side effects and causes
      leading to discontinuation were recorded. RESULTS: Infliximab caused a rapid,
      persistent improvement at all the assessment times in the BASDAI 50 (71.4 %) and
      ASDAS scores (97.1 % in ASAS20, 80 % in ASAS40, 80 % in ASAS5/6), and already
      within 6 months of beginning treatment in 50 % percent of the patients. The other
      50 % withdrew because of: adverse events (12 = 34.3 %), side effects (5 = 14.3
      %), drug inefficacy (12 = 34.3 %), spontaneously (4 = 11.4 %). Those who did not
      respond were prevalently females (34.3 % vs 17.1 %). CONCLUSION: Factors such as
      female sex, use of steroids, persistently high inflammatory levels, BASFI and
      BASDAI indices were found to be negative predictors of treatment response.
      Infliximab was found to be safe, effective and well-tolerated; it elicited
      satisfactory long term response and drug survival rates.

PMID- 26205001
TI  - Prognostic significance of neutrophil-to-lymphocyte ratio in non-small cell lung
      cancer: a meta-analysis.
AB  - Published data on the prognostic significance of neutrophil-to-lymphocyte ratio
      (NLR) in non-small cell lung cancer (NSCLC) are controversial. We performed a
      meta-analysis to more accurately assess its prognostic value. The analysis was
      performed based on the data from 14 studies with 3,656 patients to estimate the
      correlation between NLR and overall survival (OS) and progression-free survival
      (PFS) in NSCLC. Hazard ratio (HR) with 95% confidence interval (CI) were
      calculated to estimate the effect. We also conducted subgroup analysis and meta
      regression analysis. The results demonstrated that elevated pretreatment NLR
      predicted poorer OS (HR: 1.70, 95% CI: 1.39-2.09) and PFS (HR: 1.63, 95% CI: 1.27
      2.09) in patients with NSCLC. Subgroup analysis indicated that cut-off value of 5
      showed consistently prognostic value. There was no significant heterogeneity or
      publication bias for OS and PFS for included studies. This meta-analysis revealed
      that elevated pretreatment NLR might be a predicative factor of poor prognosis
      for NSCLC patients. 

PMID- 26205003
TI  - On the role of gut bacteria and infant diet in the development of autoimmunity
      for type 1 diabetes. Reply to Hanninen ALM and Toivonen RK [letter].

PMID- 26205004
TI  - Positive association between artificially sweetened beverage consumption and
      incidence of diabetes. Reply to Sylvetsky Meni AC, Swithers SE, Rother KI
      [letter].

PMID- 26205002
TI  - Burden of chronic kidney disease in resource-limited settings from Peru: a
      population-based study.
AB  - BACKGROUND: The silent progression of chronic kidney diseases (CKD) and its
      association with other chronic diseases, and high treatment costs make it a great
      public health concern worldwide. The population burden of CKD in Peru has yet to
      be fully described. METHODS: We completed a cross sectional study of CKD
      prevalence among 404 participants (total study population median age 54.8 years,
      50.2 % male) from two sites, highly-urbanized Lima and less urbanized Tumbes, who
      were enrolled in the population-based CRONICAS Cohort Study of cardiopulmonary
      health in Peru. Factors potentially associated with the presence of CKD were
      explored using Poisson regression, a statistical methodology used to determine
      prevalence ratios. RESULTS: In total, 68 participants (16.8 %, 95 % CI 13.5-20.9
      %) met criteria for CKD: 60 (14.9%) with proteinuria, four (1%) with eGFR < 60
      mL/min/1.73 m2 , and four (1%) with both. CKD prevalence was higher in Lima (20.7
      %, 95 % CI 15.8-27.1) than Tumbes (12.9 %, 95 % CI 9.0-18.5). Among participants
      with CKD, the prevalence of diabetes and hypertension was 19.1 % and 42.7 %,
      respectively. After multivariable adjustment, CKD was associated with older age,
      female sex, greater wealth tertile (although all wealth strata were below the
      poverty line), residence in Lima, and presence of diabetes and hypertension.
      CONCLUSIONS: The high prevalence rates of CKD identified in Lima and Tumbes are
      similar to estimates from high-income settings. These findings highlight the need
      to identify occult CKD and implement strategies to prevent disease progression
      and secondary morbidity.

PMID- 26205005
TI  - Evaluation of bone marrow aspirates in patients with acute myeloid leukemia at
      day 14 of induction therapy.
AB  - BACKGROUND: Early assessment of response to chemotherapy in acute myeloid
      leukemia may be performed by examining bone marrow aspirate (BMA) or biopsy
      (BMB); a hypocellular bone marrow sample indicates adequate anti-leukemic
      activity. We sought to evaluate the quantitative and qualitative assessment of
      BMA performed on day 14 (D14) of chemotherapy, to verify the inter-observer
      agreement, to compare the results of BMA and BMB, and to evaluate the impact of
      D14 blast clearance on the overall survival (OS). METHODS: A total of 107
      patients who received standard induction chemotherapy and had bone marrow samples
      were included. BMA evaluation was performed by two observers using two methods:
      quantitative assessment and a qualitative (Likert) scale. ROC curves were
      obtained correlating the BMA quantification of blasts and the qualitative scale,
      by both observers, with BMB result as gold-standard. RESULTS: There was a
      significant agreement between the two observers in both the qualitative and
      quantitative assessments (Kw = 0.737, p < 0.001, and rs = 0.798, p < 0.001; ICC =
      0.836, p < 0.001, respectively). The areas under the curve (AUC) were 0.924 and
      0.946 for observer 1 and 0.867 and 0.870 for observer 2 for assessments of the
      percentage of blasts and qualitative scale, respectively. The best cutoff for
      blast percentage in BMA was 6% and 7% for observers 1 and 2, respectively. A
      similar analysis for the qualitative scale showed the best cutoff as "probably
      infiltrated". Patients who attained higher grades of cytoreduction on D14 had
      better OS. CONCLUSIONS: Evaluation of D14 BMA using both methods had a
      significant agreement with BMB and between observers, identifying a population of
      patients with poor outcome.

PMID- 26205007
TI  - An efficient catalyst-free Mukaiyama-aldol reaction of fluorinated enol silyl
      ethers with tryptanthrin.
AB  - We report an efficient Mukaiyama-aldol reaction of tryptanthrin with fluorinated
      enol silyl ethers, which is carried out in methanol without the use of any
      catalyst. This method is applied to the total synthesis of the difluoro analogues
      of the natural product Phaitanthrin B. 

PMID- 26205008
TI  - A case of acute distal cyanosis during percutaneous catheterization of the dorsal
      metatarsal artery in a goose (Anser anser).

PMID- 26205013
TI  - Cutaneous thrombosis as the presenting finding of paroxysmal nocturnal
      haemoglobinuria.

PMID- 26205006
TI  - Preventing mental illness: closing the evidence-practice gap through workforce
      and services planning.
AB  - BACKGROUND: Mental illness is prevalent across the globe and affects multiple
      aspects of life. Despite advances in treatment, there is little evidence that
      prevalence rates of mental illness are falling. While the prevention of
      cardiovascular disease and cancers are common in the policy dialogue and in
      service delivery, the prevention of mental illness remains a neglected area.
      There is accumulating evidence that mental illness is at least partially
      preventable, with increasing recognition that its antecedents are often found in
      infancy, childhood, adolescence and youth, creating multiple opportunities into
      young adulthood for prevention. Developing valid and reproducible methods for
      translating the evidence base in mental illness prevention into actionable policy
      recommendations is a crucial step in taking the prevention agenda forward.
      METHOD: Building on an aetiological model of adult mental illness that emphasizes
      the importance of intervening during infancy, childhood, adolescence and youth,
      we adapted a workforce and service planning framework, originally applied to
      diabetes care, to the analysis of the workforce and service structures required
      for best-practice prevention of mental illness. RESULTS: The resulting framework
      consists of 6 steps that include identifying priority risk factors, profiling the
      population in terms of these risk factors to identify at-risk groups, matching
      these at-risk groups to best-practice interventions, translation of these
      interventions to competencies, translation of competencies to workforce and
      service estimates, and finally, exploring the policy implications of these
      workforce and services estimates. The framework outlines the specific tasks
      involved in translating the evidence-base in prevention, to clearly actionable
      workforce, service delivery and funding recommendations. CONCLUSIONS: The
      framework describes the means to deliver mental illness prevention that the
      literature indicates is achievable, and is the basis of an ongoing project to
      model the workforce and service structures required for mental illness
      prevention.

PMID- 26205014
TI  - The prognostic importance of the number of metastases in pulmonary metastasectomy
      of colorectal cancer.
AB  - BACKGROUND: The presence of multiple metastatic pulmonary nodules is a predictor
      of poor survival after pulmonary metastasectomy. However, there is a paucity of
      data addressing the exact number of pulmonary metastases over which prognosis
      becomes grave. The aim of our study is to investigate the prognosis of pulmonary
      metastasectomy from colorectal cancer (CRC) depending on the number of pulmonary
      metastases. METHODS: Patients who had undergone pulmonary metastasectomy for CRC
      between November 1994 and December 2013 were included. Survival and recurrence
      patterns were analyzed with regard to the number of pulmonary metastases.
      Patients were divided into three groups depending on the number of pulmonary
      metastases that were detected by the final pathologic report: group I--single
      metastasis; group II--2-3 metastases; and group III--4+ metastases. RESULTS: A
      total of 615 patients who had undergone pulmonary metastasectomy from colorectal
      cancer were included. The median follow-up period was 31 months (range 2-211
      months). The median disease-free interval (DFI) from the time of the primary
      operation for colorectal cancer was 20 months (range 0-209 months). There were
      414 patients in group I (single metastasis), 159 in group II (2-3 metastases),
      and 42 in group III (4+ metastases). The overall 5-year survival rate was 64.2%.
      The 5-year survival rates in groups I, II, and III were 70.0, 56.2, and 33.7%,
      respectively (group I vs. II, p<0.001; group II vs. III, p=0.012). The 5-year
      recurrence-free rates were 39.5, 30.6, and 8.5% in groups I, II, and III,
      respectively (group I vs. II, p<0.001; group II vs. III, p=0.056). Multivariable
      analysis revealed that age, multiple pulmonary nodules, thoracic lymph node
      metastasis, and adjuvant chemotherapy are independent predictors of survival.
      CONCLUSIONS: The overall survival and recurrence after pulmonary metastasectomy
      for CRC is dependent on the number of metastases. Surgical treatment can be
      offered to patients with three or fewer pulmonary metastases. However, more
      meticulous patient selection is required to decide whether a surgical approach is
      feasible in patients with four or more pulmonary metastases.

PMID- 26205015
TI  - Integrating yoga in mental health services.

PMID- 26205016
TI  - Repeat voluntary non-remunerated blood donor is the best quality indicator for
      blood safety.

PMID- 26205017
TI  - Yoga- a potential solution for diabetes & metabolic syndrome.

PMID- 26205018
TI  - Intimate partner violence against women in slums in India.

PMID- 26205019
TI  - Genetic markers, genotyping methods & next generation sequencing in Mycobacterium
      tuberculosis.
AB  - Molecular epidemiology (ME) is one of the main areas in tuberculosis research
      which is widely used to study the transmission epidemics and outbreaks of
      tubercle bacilli. It exploits the presence of various polymorphisms in the genome
      of the bacteria that can be widely used as genetic markers. Many DNA typing
      methods apply these genetic markers to differentiate various strains and to study
      the evolutionary relationships between them. The three widely used genotyping
      tools to differentiate Mycobacterium tuberculosis strains are IS6110 restriction
      fragment length polymorphism (RFLP), spacer oligotyping (Spoligotyping), and
      mycobacterial interspersed repeat units - variable number of tandem repeats (MIRU
      VNTR). A new prospect towards ME was introduced with the development of whole
      genome sequencing (WGS) and the next generation sequencing (NGS) methods, where
      the entire genome is sequenced that not only helps in pointing out minute
      differences between the various sequences but also saves time and the cost. NGS
      is also found to be useful in identifying single nucleotide polymorphisms (SNPs),
      comparative genomics and also various aspects about transmission dynamics. These
      techniques enable the identification of mycobacterial strains and also facilitate
      the study of their phylogenetic and evolutionary traits. 

PMID- 26205020
TI  - Interleukin-6, vitamin D & diabetes risk-factors modified by a short-term yoga
      based lifestyle intervention in overweight/obese individuals.
AB  - BACKGROUND & OBJECTIVES: Several diabetes prevention programmes have demonstrated
      a reduction in incidence of diabetes in individuals with prediabetes through
      weight loss. Short-term yoga-based lifestyle intervention programmes have also
      been shown to be efficacious in weight loss. This study was undertaken to
      investigate if interleukin (IL)-6, vitamin D, neopterin, vaspin, and diabetes
      risk factors can be modified by a short-term yoga-based lifestyle intervention in
      overweight/obese subjects. METHODS: In this pilot study, 34 overweight/obese
      [body mass index (BMI) >= 23 to <35 kg/m [2] per Asian cut-off values]
      individuals were enrolled, and received directly supervised intervention for 10
      days. Thereafter, they were advised to follow this yoga-based lifestyle at home
      for one month, and were reassessed for study variables at day 30. RESULTS: There
      was a reduction from baseline to day 10 in weight ( p <0.001), BMI ( P <0.001),
      waist/hip-ratio ( P <0.05), blood glucose ( P <0.01), and a significant
      improvement in lipid profile. There was a decrease in median fasting insulin ( P
      <0.05), homeostatic model assessment-insulin resistance ( P <0.01), and IL-6 ( Pp
      <0.05). A non-significant increase in 25-OH-vitamin D, and a decrease in
      neopterin and vaspin were observed. Twenty subjects returned for follow up
      assessments. At day 30, weight loss was sustained while systolic blood pressure
      also showed reduction ( P <0.05). Changes in vitamin D levels were significantly
      and negatively correlated with changes in weight, BMI and fasting blood glucose,
      and positively with change in high density lipoprotein. Changes in body weight
      and BMI significantly and positively correlated with insulin. Changes in IL-6
      levels positively and significantly correlated with change in neopterin levels.
      INTERPRETATION & CONCLUSIONS: The findings showed that IL-6, vitamin D, and
      diabetes risk factors were favourably modified by a short-term yoga-based
      lifestyle intervention in obesity. This study also highlighted the challenges in
      compliance associated with the follow up of subjects following an aggressive
      supervised intervention of 10 days.

PMID- 26205021
TI  - Socio-demographic factors associated with domestic violence in urban slums,
      Mumbai, Maharashtra, India.
AB  - BACKGROUND & OBJECTIVES: Domestic violence is identified as a public heath
      problem. It is associated with adverse maternal health. This study examined the
      prevalence and determinants of domestic violence among women in urban slums of
      Mumbai, India. METHODS: A community based cross-sectional household survey was
      carried out among eligible women for the study during September 2012 to January
      2013. A total of 1137 currently married women aged 18-39 yr with unmet need for
      family planning and having at least one child were selected using cluster
      systematic random sampling from two urban slums. Information on socio
      demographic, reproductive and domestic violence was collected through face-to
      face interview using a pretested structured questionnaire after obtaining
      informed written consent. Bivariate and multivariate analyses were carried out to
      find the socio-demographic factors associated with ever experienced domestic
      violence among women. RESULTS: The prevalence of women ever experiencing domestic
      violence in the community was 21.2 per cent. Women whose husband consumed alcohol
      [RR: 2.17, (95% CI: 1.58-2.98)] were significantly at an increased risk of ever
      experiencing domestic violence than their counterparts. Risk of domestic violence
      was twice [RR: 2.00, (95% CI: 1.35-2.96)] for women who justified wife beating
      than women who did not justify wife beating. INTERPRETATION & CONCLUSIONS: The
      findings showed that domestic violence was prevalent in urban slums. Factors like
      early marriage, working status, justified wife beating and husbands use of
      alcohol were significantly associated with domestic violence.

PMID- 26205022
TI  - Widespread inequalities in smoking & smokeless tobacco consumption across wealth
      quintiles in States of India: Need for targeted interventions.
AB  - BACKGROUND & OBJECTIVES: India is a large country with each State having distinct
      social, cultural and economic characteristics. Tobacco epidemic is not uniform
      across the country. There are wide variations in tobacco consumption across age,
      sex, regions and socio-economic classes. This study was conducted to understand
      the wide inequalities in patterns of smoking and smokeless tobacco consumption
      across various States of India. METHODS: Analysis was conducted on Global Adult
      Tobacco Survey, India (2009-2010) data. Prevalence of both forms of tobacco use
      and its association with socio-economic determinants was assessed across States
      and Union Territories of India. Wealth indices were calculated using socio
      economic data of the survey. Concentration index of inequality and one way ANOVA
      assessed economic inequality in tobacco consumption and variation of tobacco
      consumption across quintiles. Multiple logistic regression was done for tobacco
      consumption and wealth index adjusting for age, sex, area, education and
      occupation. RESULTS: Overall prevalence of smoking and smokeless tobacco
      consumption was 13.9 per cent (14.6, 13.3) and 25.8 per cent (26.6, 25.0),
      respectively. Prevalence of current smoking varied from 1.6 per cent (richest
      quintile in Odisha) to 42.2 per cent (poorest quintile in Meghalaya). Prevalence
      of current smokeless tobacco consumption varied from 1.7 per cent (richest
      quintile in Jammu and Kashmir) to 59.4 per cent (poorest quintile in Mizoram).
      Decreasing odds of tobacco consumption with increasing wealth was observed in
      most of the States. Reverse trend of tobacco consumption was observed in
      Nagaland. Significant difference in odds of smoking and smokeless tobacco
      consumption with wealth quintiles was observed. Concentration index of inequality
      was significant for smoking tobacco -0.7 (-0.62 to-0.78) and not significant for
      smokeless tobacco consumption -0.15 (0.01 to-0.33) INTERPRETATION & CONCLUSIONS:
      The findings of our analysis indicate that tobacco control policy and public
      health interventions need to consider widespread socio-economic inequities in
      tobacco consumption across the States in India.

PMID- 26205023
TI  - Treatment of vitamin D deficiency is an effective method in the elimination of
      asymptomatic bacterial vaginosis: A placebo-controlled randomized clinical trial.
AB  - BACKGROUND & OBJECTIVES: Bacterial vaginosis (BV) is the most prevalent vaginal
      infection in women of reproductive age group which has been found to be
      associated with vitamin D deficiency. The purpose of this study was to
      investigate the effectiveness of the administration of 2000 IU/day edible vitamin
      D for 15 wk to eliminate asymptomatic BV among reproductive age women with
      vitamin D deficiency. METHODS: A total of 208 women with asymptomatic BV, who
      were found to be eligible after interviews and laboratory tests, were randomly
      assigned to a control group (n=106) or an intervention group (n=105). They used
      vitamin D drops daily for 105 days. Vaginal and blood samples were taken before
      and after the second intervention using identical methods (Nugent score for BV
      diagnosis, serum 25-hydroxyvitamin D for vitamin D determination). RESULTS: The
      cure rate of asymptomatic BV was 63.5 per cent in the intervention and 19.2 per
      cent in the control group (P <0.001). The results showed that being unmarried
      (P=0.02), being passive smoker (P<0.001), and being in the luteal phase of a
      menstrual cycle during sampling (P=0.01) were significantly associated with post
      intervention BV positive results. After these elements were controlled, the odds
      of BV positive results in the control group was 10.8 times more than in the
      intervention group (P<0.001). INTERPRETATION & CONCLUSIONS: Among women in
      reproductive age group with vitamin D deficiency, the administration of 2000
      IU/day edible vitamin D was effective in eliminating asymptomatic BV. This
      treatment could be useful in preventing the symptoms and side effects of BV.

PMID- 26205024
TI  - Role of ATP-dependent K channels in the effects of erythropoietin in renal
      ischaemia injury.
AB  - BACKGROUND & OBJECTIVES: Erythropoietin (EPO) has cytoprotective and anti
      apoptotic effects in pathological conditions, including hypoxia and ischaemia
      reperfusion injury. One of the targets to protect against injury is ATP-dependent
      potassium (KATP ) channels. These channels could be involved in EPO induced
      ischaemic preconditoning like a protective effect. We evaluated the cell
      cytoprotective effects of EPO in relation to KATP channel activation in the renal
      tubular cell culture model under hypoxic/normoxic conditions. METHODS: Dose and
      time dependent effects of EPO, KATP channel blocker glibenclamide and KATP
      channel opener diazoxide on cellular proliferation were evaluated by colorimetric
      assay MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] under
      normoxic and hypoxic conditions in human renal proximal tubular cell line (CRL
      2830). Evaluation of the dose and time dependent effects of EPO, glibenclamide
      and diazoxide on apoptosis was done by caspase-3 activity levels. Hypoxia
      inducible factor-1 alpha (HIF-1 alpha) mRNA levels were measured by semi
      quantative reverse transcription polymerase chain reaction (RT)-PCR. Kir 6.1
      protein expresion was evalutaed by Western blot. RESULTS: Glibenclamide treatment
      decreased the number of living cells in a time and dose dependent manner, whereas
      EPO and diazoxide treatments increased. Glibenclamide (100 MUM) treatment
      significantly blocked the anti-apoptotic effects of EPO (10 IU/ml) under both
      normoxic and hypoxic conditions. EPO (10 IU/ml) and diazoxide (100 MUM)
      treatments significantly increased (p <0.01) whereas glibenclamide decreased (
      p<0.05) HIF-1 alpha mRNA expression. Glibenclamide significantly ( p<0.01)
      decreased EPO induced HIF-1 alpha mRNA expression when compared with the EPO
      alone group. INTERPRETATION & CONCLUSIONS: Our results showed that the cell
      proliferative, cytoprotective and anti-apoptotic effects of EPO were associated
      with KATP channels in the renal tubular cell culture model under hypoxic/normal
      conditions.

PMID- 26205025
TI  - Emergence of integron borne PER-1 mediated extended spectrum cephalosporin
      resistance among nosocomial isolates of Gram-negative bacilli.
AB  - BACKGROUND & OBJECTIVES: Pseudomonas extended resistant (PER) enzymes are rare
      type of extended-spectrum beta lactamases (ESBLs) that confer third generation
      cephalosporin resistance. These are often integron borne and laterally
      transmitted. The aim of the present study was to investigate the emergence of
      integron borne cephalosporin resistant PER-1 gene in diverse incompatibility
      (Inc) group plasmids among Gram-negative bacteria. METHODS: A total of 613
      consecutive, non-duplicate, Gram-negative bacteria of Enterobacteriaceae family
      and non-fermenting Gram-negative bacteria were isolated from different clinical
      specimens during a period of 18 months. For amplification and detection of
      blaPER, multiplex PCR was done. For understanding the genetic environment of
      blaPER-1, integrase gene PCR and cassette PCR (59 be) was performed. Gene
      transferability experiment was carried out and PCR based replicon typing was
      performed for incompatibility group typing of plasmids using 18 pairs of primers.
      An inhibitor based method was used for phenotypic detection of intrinsic
      resistance. RESULTS: Multiplex PCR and sequencing confirmed that 45 isolates were
      harbouring blaPER-1. Both class 1 and class 2 integrons were observed among them.
      Integrase and cassette PCR (59 be) PCR results confirmed that the resistant
      determinant was located within class 1 integron. Transformation and conjugation
      experiments revealed that PER-1 was laterally transferable and disseminated
      through diverse Inc plasmid type. Efflux pump mediated carbapenem resistance was
      observed in all isolates. All isolates belonged to heterogenous groups.
      INTERPRETATION & CONCLUSIONS: This study demonstrates the dissemination of
      cephalosporins resistant, integron borne blaPER-1 in hospital setting in this
      part of the country and emphasizes on the rational use of third generation
      cephalosporins to slow down the expansion of this rare type of ESBL gene.

PMID- 26205027
TI  - Performance of tests for identification of Neisseria gonorrhoeae.

PMID- 26205026
TI  - Curcuma oil ameliorates insulin resistance & associated thrombotic complications
      in hamster & rat.
AB  - BACKGROUND & OBJECTIVES: Curcuma oil (C. oil) isolated from turmeric (Curcuma
      longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and
      anti-hyperlipidaemic effects in experimental animal models. However, its effect
      in insulin resistant animals remains unclear. The present study was carried out
      to investigate the disease modifying potential and underlying mechanisms of the
      C. oil in animal models of diet induced insulin resistance and associated
      thrombotic complications. METHODS: Male Golden Syrian hamsters on high fructose
      diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or
      C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were
      treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the
      protective effect of C. oil, blood glucose, serum insulin, platelet aggregation,
      thrombosis and inflammatory markers were assessed in these animals. RESULTS:
      Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia,
      hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid
      peroxidation, inflammation, endothelial dysfunction, platelet free radical
      generation, tyrosine phosphorylation, aggregation, adhesion and intravascular
      thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated
      HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative
      stress, inflammation, endothelial dysfunction, platelet activation, and
      thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was
      comparable with the standard drug fenofibrate. Curcuma oil treatment in the last
      two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by
      modulating hepatic expression of sterol regulatory element binding protein 1c
      (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC
      1)alpha and PGC-1beta genes known to be involved in lipid and glucose metabolism.
      INTERPRETATION & CONCLUSIONS: High fructose feeding to rats and hamsters led to
      the development of insulin resistance, hyperglycaemia, endothelial dysfunction
      and oxidative stress. C. oil prevented development of thrombotic complications
      associated with insulin resistance perhaps by modulating genes involved in lipid
      and glucose metabolism. Further studies are required to confirm these findings.

PMID- 26205028
TI  - Mutations in gyrA & parC genes of Shigella flexneri 2a determining the
      fluoroquinolone resistance.

PMID- 26205029
TI  - Conducting placebo controlled randomized trials.

PMID- 26205030
TI  - Association between vitamin D deficiency & paediatric tuberculosis.

PMID- 26205031
TI  - Role of genetic variants of vitamin D immunomodulation genes in clinical response
      to treatment of tuberculosis.

PMID- 26205032
TI  - Evaluation of vitamin D levels in Indian children with intrathoracic
      tuberculosis.

PMID- 26205033
TI  - Lumbar hernia of Grynfeltt's triangle.

PMID- 26205035
TI  - Erratum.

PMID- 26205034
TI  - Trephine biopsy in an elderly man revealed double pathology.

PMID- 26205036
TI  - Cells from the hematopoietic lineage are only present transiently during healing
      in a mouse model of non-severe burn injury.
AB  - INTRODUCTION: The aim of our study is to identify the contribution of
      hematopoietic-derived cells to burn-wound healing in a non-severe injury. There
      are many conflicting reports of the contribution of bone marrow-derived cells to
      wound healing and whether these are hematopoietic or mesenchymal in origin. The
      role of hematopoietic lineage cells is investigated in this study in the context
      of the response to burn injury. METHODS: Transgenic mice expressing the LacZ
      reporter gene in all cells of the hematopoietic lineage underwent a non-severe
      full-thickness burn injury (8 % of total body surface area). Wounds were assessed
      for LacZ-positive cells at days 7, 14, and 28 post-injury by using whole-mount
      staining. Cells were also cultured from the wounds at each time point and
      analysed for expression of fibroblast and myofibroblast markers. RESULTS: At day
      7, positive cells were identified in the wounds representing the inflammatory
      response. Some dermal cells were also identified at this early stage. At day 14,
      positive cells were also identified and were cultured from the wound tissue
      samples. However, by day 28, no positive cells could be detected or cultured from
      the healed wound tissue. Isolated LacZ-positive cells did not express collagen 1
      or alpha-smooth muscle actin proteins, indicating that they had not
      differentiated into dermal fibroblast-type cells. CONCLUSIONS: In this model of
      burn injury, hematopoietic lineage cells were present in the healing wound only
      transiently and did not appear to contribute to the long-term scar population.
      This is in contrast with reports demonstrating that fibrocytes contribute a long
      term sustained population in scar tissue. This work demonstrates that in a non
      severe burn injury model there is a sustained transient contribution of
      hematopoietic cells to the healed wound. Further characterisation of the types
      and extent of wounding required to establish a long-term hematopoietic response
      will be important in determining future cell-based therapies.

PMID- 26205037
TI  - Retrospective study of the prevalence and progression of monoclonal gammopathy in
      HIV positive versus HIV negative patients.
AB  - The significance of HIV associated paraproteins and their risk of progression to
      hematological malignancies remains unclear. We compared the development of
      hematological malignancies among HIV+ (n = 266) and HIV- (n = 537) patients with
      monoclonal gammopathies. HIV+ and HIV- patients with a positive serum protein
      electrophoresis test (SPEP) were studied. HIV+ SPEP+ were more likely to have
      faint and oligoclonal paraproteins (F-SPEP) and less likely to have discrete
      bands (D-SPEP) compared to HIV- SPEP+. The incidence of hematological
      malignancies was significantly lower in the HIV+ compared to the HIV- (6.4% vs
      15.4%, p < 0.0002). Upon subgroup analysis, the lower incidence of hematological
      malignancies was noted for HIV+ patients with F-SPEP but not for those with D
      SPEP. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26205038
TI  - Low molecular weight guluronate prevents TNF-alpha-induced oxidative damage and
      mitochondrial dysfunction in C2C12 skeletal muscle cells.
AB  - Muscle wasting is associated with a variety of chronic or inflammatory disorders.
      Evidence suggests that inflammatory cytokines play a vital role in muscle
      inflammatory pathology and this may result in oxidative damage and mitochondrial
      dysfunction in skeletal muscle. In our study, we used microwave degradation to
      prepare a water-soluble low molecular weight guluronate (LMG) of 3000 Da from
      Fucus vesiculosus obtained from Canada, the Atlantic Ocean. We demonstrated the
      structural characteristics, using HPLC, FTIR and NMR of LMG and investigated its
      effects on oxidative damage and mitochondrial dysfunction in C2C12 skeletal
      muscle cells induced by tumor necrosis factor alpha (TNF-alpha), a cell
      inflammatory cytokine. The results indicated that LMG could alleviate
      mitochondrial reactive oxygen species (ROS) production, increase the activities
      of antioxidant enzymes (GSH and SOD), promote mitochondrial membrane potential
      (MMP) and upregulate the expression of mitochondrial respiratory chain protein in
      TNF-alpha-induced C2C12 cells. LMG supplement also increased the mitochondrial
      DNA copy number and mitochondrial biogenesis related genes in TNF-alpha-induced
      C2C12 cells. LMG may exert these protective effects through the nuclear factor
      kappa B (NF-kappaB) signaling pathway. These suggest that LMG is capable of
      protecting TNF-alpha-induced C2C12 cells against oxidative damage and
      mitochondrial dysfunction. 

PMID- 26205039
TI  - Total Syntheses and Biological Evaluation of Both Enantiomers of Several
      Hydroxylated Dimeric Nuphar Alkaloids.
AB  - Herein, we describe the first total syntheses of five members of the dimeric
      nuphar alkaloids: (+)-6,6'-dihydroxythiobinupharidine (+)-1 a, (+)-6
      hydroxythiobinupharidine (+)-1 b, (-)-6,6'-dihydroxythionuphlutine (-)-2 a, (-)
      6,6'-dihydroxyneothiobinupharidine (-)-3 a, and (+)-6,6'
      dihydroxyneothionuphlutine (+)-4 a. The latter two have not been found in nature.
      We have also made each of their enantiomers (-)-1 a-b, (+)-2 a, (+)-3 a, and (-)
      4 a. The key step in these syntheses was the dimerization of an alpha
      aminonitrile (a hydrolytically stable surrogate for its corresponding hemiaminal)
      with chiral Lewis acid complexes. We have also reassigned the literature
      structures of (+)-1 a-1 b-for those instances in which the NMR spectra were
      obtained in CD3OD-to their corresponding CD3O-adducts. Our efforts provide for
      the first time apoptosis data for (-)-3 a, (+)-4 a, and all five non-natural
      enantiomers prepared. The data indicate high apoptotic activity regardless of the
      enantiomer or relative stereochemical configuration at C7 and C7'.

PMID- 26205040
TI  - Nacre biomineralisation: A review on the mechanisms of crystal nucleation.
AB  - The wide diversity of biogenic minerals that is found in nature, each with its
      own morphology, mechanical properties and composition, is remarkable. In order to
      produce minerals that are optimally adapted for their function, biomineralisation
      usually occurs under strict cellular control. This control is exerted by
      specialised proteins and polysaccharides that assemble into a 3-dimensional
      organic matrix framework, forming a microenvironment where mineral deposition
      takes place. Molluscs are unique in that they use a striking variety of
      structural motifs to build their shells, each made of crystals with different
      morphologies and different calcium carbonate polymorphs. Much of want is known
      about mollusc shell formation comes from studies on the nacreous layer, or mother
      of-pearl. In this review, we discuss two existing models on the nucleation of
      aragonite crystals during nacre formation: heteroepitaxial nucleation and mineral
      bridges. The heteroepitaxial nucleation model is based on the identification of
      chemical functional groups and aragonite-nucleating proteins at the centre of
      crystal imprints. It proposes that during nacre formation, each aragonite tablet
      nucleates independently on a nucleation site that is formed by acidic proteins
      and/or glycoproteins adsorbed on the chitin scaffold. The mineral bridges model
      is based on the identification of physical connections between the crystals in a
      stack, which results in a large number of crystals across several layers sharing
      the same crystallographic orientation. These observations suggest that there is
      one nucleation event per stack of tablets. Once the first crystal nucleates and
      reaches the top interlamellar matrix, it continues growing through pores, giving
      rise to the next layer of nacre, subsequently propagating into a stack. We
      compare both models and propose that they work in concert to control crystal
      nucleation in nacre. De novo crystal nucleation has to occur at least once per
      stack of aligned crystals, and is induced by nucleation sites. We suggest that
      further growth is controlled both by mineral bridges and nucleation sites.
      Finally, we discuss the role of amorphous calcium carbonate precursor in nacre
      formation. 

PMID- 26205041
TI  - Proposal for standardized ultrasound descriptors of abnormally invasive placenta
      (AIP).

PMID- 26205044
TI  - Investigation of the Sedimentation Behavior of Aluminum Phosphate: Influence of
      pH, Ionic Strength, and Model Antigens.
AB  - Evaluation of the physical characteristics of vaccines formulated in the presence
      of adjuvants, such as aluminum salts (Alum), is an important step in the
      development of vaccines. Depending on the formulation conditions and the
      associated electrostatic interactions of the adjuvant particles, the vaccine
      suspension may transition between flocculated and deflocculated states. The
      impact of practical formulation parameters, including pH, ionic strength, and the
      presence of model antigens, has been correlated to the sedimentation behavior of
      aluminum phosphate suspensions. A novel approach for the characterization of
      suspension properties of Alum has been developed to predict the flocculated state
      of the system using a sedimentation analysis-based tool (Turbiscan(r)). Two
      sedimentation parameters, the settling onset time (Sonset) and the sedimentation
      volume ratio (SVR) can be determined simultaneously in a single measurement. The
      results demonstrate the suspension characteristics to be significantly altered by
      solution conditions (pH and ionic strength) and the charge state of bound
      antigens. Formulation conditions that promote the flocculated state of the
      suspension are characterized by faster Sonset and higher SVR, and are generally
      easy to resuspend. The Turbiscan(r) method described herein is a useful tool for
      the characterization of aluminum-containing suspensions and may be adapted for
      screening and optimization of suspension-based vaccine formulations in general.

PMID- 26205045
TI  - Antiallodynic and antihyperalgesic effects of zerumbone on a mouse model of
      chronic constriction injury-induced neuropathic pain.
AB  - Neuropathic pain is a chronic condition that is difficult to be treated. Current
      therapies available are either ineffective or non-specific thus requiring newer
      treatment approaches. In this study, we investigated the antiallodynic and
      antihyperalgesic effects of zerumbone, a bioactive sesquiterpene from Zingiber
      zerumbet in chronic constriction injury (CCI)-induced neuropathic pain animal
      model. Our findings showed that single and repeated dose of intra-peritoneal
      administration of zerumbone (5, 10, 50, 100 mg/kg) significantly attenuated the
      CCI-induced neuropathic pain when evaluated using the electronic von Frey
      anesthesiometer, cold plate, Randall-Selitto analgesiometer and the Hargreaves
      plantar test. Zerumbone significantly alleviated tactile and cold allodynia as
      well as mechanical and thermal hyperalgesia. Our findings are in comparison to
      the positive control drugs thatused gabapentin (20 mg/kgi.p.) and morphine (1
      mg/kgi.p.). Together, these results showed that the systemic administration of
      zerumbone produced marked antiallodynic and antihyperalgesic effects in the CCI
      induced neuropathic pain in mice and may serve as a potential lead compound for
      further analysis.

PMID- 26205046
TI  - Ultrasound accurately identifies soft tissue foreign bodies in a live
      anesthetized porcine model.
AB  - BACKGROUND: Some subcutaneous foreign bodies (FBs) are not easily visualized
      during physical examination and may not be detected on radiographic evaluation.
      Ultrasound (US) is capable of visualizing FBs of varying compositions. Previous
      studies have examined the use of US to detect FBs in deceased animal or human
      tissue. This study used live anesthetized porcine tissue to more closely model
      clinical conditions. OBJECTIVES: The objectives were to examine the test
      characteristics of US in the evaluation of FBs in living tissue and to evaluate
      if secondary findings such as surrounding edema and hematoma improve diagnostic
      accuracy. METHODS: Institutional Animal Care and Use Committee (IACUC) approval
      was obtained. FBs 1 cm in length and 1 to 3 mm in width were created from
      toothpicks (wood), 21-gauge needles (metal), and a broken ampule (glass) and
      inserted subcutaneously into an anesthetized 20-kg Yorkshire swine. There were 72
      sites implanted with equal proportions of each FB type and null sites. Half of
      the FBs were inserted at time 0 and half were inserted after 2 hours. Immediately
      after placement, four blinded physicians performed US evaluations of the first 36
      sites. At 2 hours after placement, they evaluated each of the original 36 sites
      and the 36 new sites. They documented the presence or absence of FBs and
      surrounding edema. RESULTS: After initial FB placement, 122 of the 144
      interpretations (85%) were correct, with a sensitivity of 85% (95% confidence
      interval [CI] = 79% to 92%) and a specificity of 86% (95% CI = 76% to 98%). No
      sites demonstrated surrounding edema. At 2 hours after placement, 127 of 144
      interpretations (88%) for these same sites were correct, with a sensitivity of
      87% (95% CI = 82% to 93%) and a specificity of 89% (95% CI = 81% to 97%). Of the
      108 observations (27 sites that contained FBs), eight of the 108 (7%)
      observations had surrounding edema (four glass, three wood, one metal). For the
      36 new sites with FBs placed 2 hours later, 126 of the 144 interpretations (83%)
      were correct, with a sensitivity of 88% (95% CI = 82% to 94%) and a specificity
      of 83% (95% CI = 73% to 95%). No sites had surrounding edema present.
      CONCLUSIONS: Ultrasound was sensitive, specific, and accurate in identifying FBs
      in live anesthetized porcine tissue. Surrounding edema or hematoma 2 hours after
      placement was so infrequently observed that it was not possible to determine its
      influence on the test characteristics.

PMID- 26205047
TI  - Potential mechanism of action of 3'-demethoxy-6-O-demethyl-isoguaiacin on
      methicillin resistant Staphylococcus aureus.
AB  - Bacterial infections represent one of the main threats to global public health.
      One of the major causative agents associated with high morbidity and mortality
      infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus.
      Therefore, there is a need to develop new antibacterial agents to treat these
      infections, and natural products are a rich source of them. In previous studies,
      we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and
      characterized from Larrea tridentate, showed the best activity towards
      methicillin-resistant S. aureus. Thus, the aim of this study was to determine the
      potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O
      demethylisoguaiacin against methicillin-resistant S. aureus using microarray
      technology. Results of microarray genome expression were validated by real-time
      polymerase chain reaction (RT-PCR). The genetic profile expression results showed
      that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane
      affecting proteins of the ATP-binding cassette (ABC) transport system causing
      bacteria death. This molecular mechanism is not present in any antibacterial
      commercial drug and could be a new target for the development of novel
      antibacterial agents. 

PMID- 26205048
TI  - Microbiological assessment, nutritional characterization and phenolic compounds
      of bee pollen from Mellipona mandacaia Smith, 1983.
AB  - This study aims to assess the microbiological parameters and the chemical
      composition of 21 samples of stingless bee pollen (Melipona mandacaia) from two
      regions of Bahia, Brazil (Joao Dourado and Uibai), with particular emphasis on
      the nutritional value, total phenols and flavonoids and fatty acids composition.
      Regarding the microbiological quality, the studied microorganisms (moulds and
      yeasts, coliforms, Escherichia coli, Staphylococcus aureus, Salmonella sp.,
      psychrotrophic and sulfite-reducing Clostridia) were absent in all samples. On
      the other hand, the values obtained for the aerobic mesophilic microorganism
      ranged from 11.0 +/- 1.0 to 1.32 +/- 1.2 cfu?g(-)(1) (JD samples) and from 282 +/
      3.82 to 688 +/- 10.1 cfu?g(-)(1) (U samples). The nutritional parameters
      (moisture, ash, water activity, pH, total acidity, protein, fiber, total
      phenolic, flavonoids and reducing sugars) were within the stipulated by law,
      except for pH and moisture content, which presented superior and inferior values,
      respectively. Polyunsaturated fatty acids (54.1%) were significantly higher than
      saturated (42.18%) and monounsaturated (3.71%). It was found that the bee pollen
      is safe from the microbiological point of view and has a good nutritional
      quality. The influence of the geographical origin on the assessed parameters was
      evident, especially concerning the fatty acid profile. 

PMID- 26205049
TI  - Anti-Inflammatory activities of licorice extract and its active compounds,
      glycyrrhizic acid, liquiritin and liquiritigenin, in BV2 cells and mice liver.
AB  - This study provides the scientific basis for the anti-inflammatory effects of
      licorice extract in a t-BHP (tert-butyl hydrogen peroxide)-induced liver damage
      model and the effects of its ingredients, glycyrrhizic acid (GA), liquiritin (LQ)
      and liquiritigenin (LG), in a lipopolysaccharide (LPS)-stimulated microglial cell
      model. The GA, LQ and LG inhibited the LPS-stimulated elevation of pro
      inflammatory mediators, such as inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta and interleukin (IL)-6 in BV2 (mouse brain microglia) cells. Furthermore,
      licorice extract inhibited the expression levels of pro-inflammatory cytokines
      (TNF-alpha, IL-1beta and IL-6) in the livers of t-BHP-treated mice models. This
      result suggested that mechanistic-based evidence substantiating the traditional
      claims of licorice extract and its three bioactive components can be applied for
      the treatment of inflammation-related disorders, such as oxidative liver damage
      and inflammation diseases. 

PMID- 26205050
TI  - Cell-type specific penetrating peptides: therapeutic promises and challenges.
AB  - Cell penetrating peptides (CPP), also known as protein transduction domains
      (PTD), are small peptides able to carry peptides, proteins, nucleic acid, and
      nanoparticles, including viral particles, across the cellular membranes into
      cells, resulting in internalization of the intact cargo. In general, CPPs can be
      broadly classified into tissue-specific and non-tissue specific peptides, with
      the latter further sub-divided into three types: (1) cationic peptides of 6-12
      amino acids in length comprised predominantly of arginine, lysine and/or
      ornithine residues; (2) hydrophobic peptides such as leader sequences of secreted
      growth factors or cytokines; and (3) amphipathic peptides obtained by linking
      hydrophobic peptides to nuclear localizing signals. Tissue-specific peptides are
      usually identified by screening of large peptide phage display libraries. These
      transduction peptides have the potential for a myriad of diagnostic as well as
      therapeutic applications, ranging from delivery of fluorescent or radioactive
      compounds for imaging, to delivery of peptides and proteins of therapeutic
      potential, and improving uptake of DNA, RNA, siRNA and even viral particles. Here
      we review the potential applications as well as hurdles to the tremendous
      potential of these CPPs, in particular the cell-type specific peptides. 

PMID- 26205051
TI  - New fluorescence probes for biomolecules.
AB  - Steady state fluorescence measurements have been used for the investigation of
      interaction between the bovine serum albumin (BSA) and fluorescence probes: 3
      hydroxy-2,4- bis[(3-methyl-1,3-benzoxazol-2(3H)-ylidene)methyl]cyclobut-2-en-1
      one (SQ6), 3-hydroxy- 2,4-bis[(3-methyl-1,3-benzothiazol-2(3H)
      ylidene)methyl]cyclobut-2-en-1-one (SQ7) and 3-hydroxy-2,4-bis[(1,3,3-trimethyl
      1,3-dihydro-2H-indol-2-ylidene)methyl]cyclobut-2-en-1-one (SQ8). The binding
      constant between bovine serum albumin and squarine dyes has been determined by
      using both the Benesi-Hildebrand and Stern-Volmer equations. The negative value
      of free energy change indicates the existence of a spontaneous complexation
      process of BSA with squarine dyes. 

PMID- 26205052
TI  - The complete chloroplast genome of Capsicum annuum var. glabriusculum using
      Illumina sequencing.
AB  - Chloroplast (cp) genome sequences provide a valuable source for DNA barcoding.
      Molecular phylogenetic studies have concentrated on DNA sequencing of conserved
      gene loci. However, this approach is time consuming and more difficult to
      implement when gene organization differs among species. Here we report the
      complete re-sequencing of the cp genome of Capsicum pepper (Capsicum annuum var.
      glabriusculum) using the Illumina platform. The total length of the cp genome is
      156,817 bp with a 37.7% overall GC content. A pair of inverted repeats (IRs) of
      50,284 bp were separated by a small single copy (SSC; 18,948 bp) and a large
      single copy (LSC; 87,446 bp). The number of cp genes in C. annuum var.
      glabriusculum is the same as that in other Capsicum species. Variations in the
      lengths of LSC; SSC and IR regions were the main contributors to the size
      variation in the cp genome of this species. A total of 125 simple sequence repeat
      (SSR) and 48 insertions or deletions variants were found by sequence alignment of
      Capsicum cp genome. These findings provide a foundation for further investigation
      of cp genome evolution in Capsicum and other higher plants. 

PMID- 26205053
TI  - Identification and expression analysis of glucosinolate biosynthetic genes and
      estimation of glucosinolate contents in edible organs of Brassica oleracea
      subspecies.
AB  - Glucosinolates are anti-carcinogenic, anti-oxidative biochemical compounds that
      defend plants from insect and microbial attack. Glucosinolates are abundant in
      all cruciferous crops, including all vegetable and oilseed Brassica species.
      Here, we studied the expression of glucosinolate biosynthesis genes and
      determined glucosinolate contents in the edible organs of a total of 12 genotypes
      of Brassica oleracea: three genotypes each from cabbage, kale, kohlrabi and
      cauliflower subspecies. Among the 81 genes analyzed by RT-PCR, 19 are
      transcription factor-related, two different sets of 25 genes are involved in
      aliphatic and indolic biosynthesis pathways and the rest are breakdown-related.
      The expression of glucosinolate-related genes in the stems of kohlrabi was
      remarkably different compared to leaves of cabbage and kale and florets of
      cauliflower as only eight genes out of 81 were expressed in the stem tissues of
      kohlrabi. In the stem tissue of kohlrabi, only one aliphatic transcription factor
      related gene, Bol036286 (MYB28) and one indolic transcription factor-related
      gene, Bol030761 (MYB51), were expressed. The results indicated the expression of
      all genes is not essential for glucosinolate biosynthesis. Using HPLC analysis, a
      total of 16 different types of glucosinolates were identified in four subspecies,
      nine of them were aliphatic, four of them were indolic and one was aromatic.
      Cauliflower florets measured the highest number of 14 glucosinolates. Among the
      aliphatic glucosinolates, only gluconapin was found in the florets of
      cauliflower. Glucoiberverin and glucobrassicanapin contents were the highest in
      the stems of kohlrabi. The indolic methoxyglucobrassicin and aromatic
      gluconasturtiin accounted for the highest content in the florets of cauliflower.
      A further detailed investigation and analyses is required to discern the precise
      roles of each of the genes for aliphatic and indolic glucosinolate biosynthesis
      in the edible organs. 

PMID- 26205054
TI  - The antioxidant activity and their major antioxidant compounds from Acanthopanax
      senticosus and A. koreanum.
AB  - The antioxidant activity and chlorogenic acid and caffeic acid contents were
      investigated from different parts of Acanthopanax senticosus and A. koreanum.
      Antioxidant activity was assessed by various in vitro assays such as DPPH, ABTS,
      FRAP, reducing power assays and ORAC, and the chlorogenic acid and caffeic acid
      were validated by HPLC chromatography. Among the various extracts, the fruit
      extracts of A. senticosus and A. koreanum exhibited strongest antioxidant
      activities including ABTS, FRAP, reducing power and ORAC, however, strongest DPPH
      radical scavenging activity was observed from the leaf extract of A. senticosus.
      In addition, the antioxidant activities of various extracts were correlated with
      total phenolic and proanthocyanidin contents. The major phenolic contents from
      various parts of these plants observed that leaf extract of A. senticosus
      expressed higher levels of chlorogenic acid (14.86 mg/dry weigh g) and caffeic
      acid (3.09 mg/dry weigh g) than other parts. Therefore, these results suggest
      that the leaf of A. senticosus may be an excellent natural source for functional
      foods and pharmaceutical agents, and the validated method was useful for the
      quality control of A. senticosus. 

PMID- 26205055
TI  - Extractions of oil from Descurainia sophia seed using supercritical CO2, chemical
      compositions by GC-MS and evaluation of the anti-tussive, expectorant and anti
      asthmatic activities.
AB  - Descurainia sophia is widely distributed in China and is one of the most
      troublesome annual weeds. It has diverse medicinal usage. D. sophia has abundant
      oil, making it an important oil plant in China. The main goal of this study was
      to obtain the maximum yield of the oil by an optimal selection of supercritical
      fluid extraction parameters. According to the central composite design and
      response surface methodology for supercritical fluid extraction method, a
      quadratic polynomial model was used to predict the yield of D. sophia seed oil. A
      series of runs was performed to assess the optimal extraction conditions. The
      results indicated that the extraction pressure had the greatest impact on oil
      yield within the range of the operating conditions studied. A total of
      approximately 67 compounds were separated in D. sophia seed oil by GC-MS, of
      which 51 compounds represented 98.21% of the total oils, for the first time. This
      study was also aimed at evaluating the anti-asthmatic, anti-tussive and
      expectorant activities in vivo of D. sophia seed oil which supplied for further
      research on bioactive constituents and pharmacological mechanisms. 

PMID- 26205056
TI  - Cell-penetrating peptides: possibilities and challenges for drug delivery in
      vitro and in vivo.
AB  - In this review, we discuss how cell-penetrating peptides (CPPs) might get access
      to their intracellular targets. We specifically focus on the challenge of
      deciding whether the positively-charged CPPs are just bound to the negatively
      charged cell surface and subsequently endocytosed or actually transported into
      the cytosol, either by direct plasma membrane penetration or after endocytosis.
      This discussion includes comments about pitfalls when using pharmacological
      inhibitors in such studies. The possibility of exploiting CPPs as carriers for
      the delivery of drugs of different sizes in vitro is discussed, as is the use of
      CPPs as carriers for therapeutic drugs or contrast agents in vivo. We conclude
      that in many cases, more studies are needed to demonstrate conclusively whether
      increased delivery of a substance attached to CPPs is due to a membrane
      penetrating property or whether the increase is a consequence of just changing
      the charge of the substance to be delivered. Finally, the expected dose needed
      for the use of such conjugates in vivo is discussed, including aspects to
      consider in order to bring potential products into clinical use. 

PMID- 26205057
TI  - Bioactive cembranoids from the South China Sea soft coral Sarcophyton elegans.
AB  - Four new cembranoids, sarcophelegans A-D (1-4) and six known analogues (5-10)
      were isolated from the South China Sea soft coral Sarcophyton elegans. Their
      structures were elucidated through detailed spectroscopic analysis, and the
      absolute configuration of 1 was confirmed by single-crystal X-ray diffraction.
      The antimigratory potential of compounds 1-10 were evaluated and compounds 2 and
      6 were found to inhibit human breast tumor MDA-MB-231 cell migration at 10 MUM. 

PMID- 26205058
TI  - Iminoiodane- and Bronsted base-mediated cross dehydrogenative coupling of cyclic
      ethers with 1,3-dicarbonyl compounds.
AB  - A one-pot, two-step approach to prepare 2-tetrahydrofuran and -pyran substituted
      1,3-dicarbonyl compounds by PhI=NTs-mediated amination/Bronsted base-catalyzed
      cross dehydrogenative coupling (CDC) reaction of the cyclic ether and 1,3
      dicarbonyl derivative under mild conditions is reported. The reaction is
      compatible with a variety of cyclic ethers and 1,3-dicarbonyl compounds,
      affording the corresponding coupled products in moderate to good yields of up to
      80% over two steps. 

PMID- 26205059
TI  - Modeling the photocatalytic mineralization in water of commercial formulation of
      estrogens 17-beta estradiol (E2) and nomegestrol acetate in contraceptive pills
      in a solar powered compound parabolic collector.
AB  - Endocrine disruptors in water are contaminants of emerging concern due to the
      potential risks they pose to the environment and to the aquatic ecosystems. In
      this study, a solar photocatalytic treatment process in a pilot-scale compound
      parabolic collector (CPC) was used to remove commercial estradiol formulations
      (17-beta estradiol and nomegestrol acetate) from water. Photolysis alone degraded
      up to 50% of estradiol and removed 11% of the total organic carbon (TOC). In
      contrast, solar photocatalysis degraded up to 57% of estrogens and the TOC
      removal was 31%, with 0.6 g/L of catalyst load (TiO2 Aeroxide P-25) and 213.6 ppm
      of TOC as initial concentration of the commercial estradiols formulation. The
      adsorption of estrogens over the catalyst was insignificant and was modeled by
      the Langmuir isotherm. The TOC removal via photocatalysis in the photoreactor was
      modeled considering the reactor fluid-dynamics, the radiation field, the
      estrogens mass balance, and a modified Langmuir-Hinshelwood rate law, that was
      expressed in terms of the rate of photon adsorption. The optimum removal of the
      estrogens and TOC was achieved at a catalyst concentration of 0.4 g/L in 29 mm
      diameter tubular CPC reactors which approached the optimum catalyst concentration
      and optical thickness determined from the modeling of the absorption of solar
      radiation in the CPC, by the six-flux absorption-scattering model (SFM). 

PMID- 26205060
TI  - In vivo antihyperglycemic activity of a lanosteryl triterpene from Protorhus
      longifolia.
AB  - Control of postprandial hyperglycemia is crucial in the management of diabetes
      mellitus. Despite the use of the current hypoglycemic drugs, incidence of
      diabetes and related diseases continue to increase. This study aimed at
      evaluating the in vivo antihyperglycemic activity of methyl-3beta-hydroxylanosta
      9,24-dien-21-oate (RA-3), a lanosteryl triterpene isolated, and characterized
      from Protorhus longifolia stem bark. Spectroscopic data analysis was used to
      establish and verify the structure of the triterpene. The antihyperglycemic
      activity of the triterpene was evaluated in an STZ-induced diabetes rat model.
      The experimental animals were orally administered with RA-3 (100 mg/kg body
      weight) daily for 14 days. An oral glucose tolerance test was also performed. The
      animals were euthanized and biochemical analysis of antioxidant status, some
      glycolytic enzymes and glycogen content were conducted on serum and liver
      samples, respectively. RA-3 exhibited hypoglycemic activity by reducing blood
      glucose levels by 37%. The triterpene also improved glucose tolerance in the
      diabetic rats. Relatively higher hepatic glycogen content, hexokinase and
      glucokinase activity with a decrease in glucose-6-phosphatase activity were
      observed in the triterpene-treated diabetic group when compared with the diabetic
      control group. The triterpene treatment further increased antioxidant status of
      the diabetic animals; increased activity of superoxide dismutase and catalase
      were observed along with a decrease in malondialdehyde content. The results
      indicate potential pharmaceutical effects of lanosteryl triterpene in the
      management of diabetes mellitus. 

PMID- 26205061
TI  - Molecular docking and structure-based drug design strategies.
AB  - Pharmaceutical research has successfully incorporated a wealth of molecular
      modeling methods, within a variety of drug discovery programs, to study complex
      biological and chemical systems. The integration of computational and
      experimental strategies has been of great value in the identification and
      development of novel promising compounds. Broadly used in modern drug design,
      molecular docking methods explore the ligand conformations adopted within the
      binding sites of macromolecular targets. This approach also estimates the ligand
      receptor binding free energy by evaluating critical phenomena involved in the
      intermolecular recognition process. Today, as a variety of docking algorithms are
      available, an understanding of the advantages and limitations of each method is
      of fundamental importance in the development of effective strategies and the
      generation of relevant results. The purpose of this review is to examine current
      molecular docking strategies used in drug discovery and medicinal chemistry,
      exploring the advances in the field and the role played by the integration of
      structure- and ligand-based methods. 

PMID- 26205062
TI  - Secondary metabolites from Rubiaceae species.
AB  - This study describes some characteristics of the Rubiaceae family pertaining to
      the occurrence and distribution of secondary metabolites in the main genera of
      this family. It reports the review of phytochemical studies addressing all
      species of Rubiaceae, published between 1990 and 2014. Iridoids, anthraquinones,
      triterpenes, indole alkaloids as well as other varying alkaloid subclasses, have
      shown to be the most common. These compounds have been mostly isolated from the
      genera Uncaria, Psychotria, Hedyotis, Ophiorrhiza and Morinda. The occurrence and
      distribution of iridoids, alkaloids and anthraquinones point out their
      chemotaxonomic correlation among tribes and subfamilies. From an evolutionary
      point of view, Rubioideae is the most ancient subfamily, followed by Ixoroideae
      and finally Cinchonoideae. The chemical biosynthetic pathway, which is not so
      specific in Rubioideae, can explain this and large amounts of both iridoids and
      indole alkaloids are produced. In Ixoroideae, the most active biosysthetic
      pathway is the one that produces iridoids; while in Cinchonoideae, it produces
      indole alkaloids together with other alkaloids. The chemical biosynthetic pathway
      now supports this botanical conclusion. 

PMID- 26205063
TI  - Cranial vault expansion with the split bone flap technique in shunt-related
      craniosynostosis.
AB  - INTRODUCTION: Shunt-related craniosynostosis causing craniocerebral disproportion
      represents a particular complication of the treatment of hydrocephalus. When the
      modification of the shunt opening pressure does not improve the symptomatology,
      surgery for correction of craniocerebral disproportion is indicated. We present
      the results and advantages of the split bi-frontal bone technique that is a
      modification of the previous used frontal bone advancement technique. PATIENTS
      AND METHODS: We retrospectively reviewed 5 patients with iatrogenic
      craniosynostosis treated in our institution from 1995 to 2012. A splitting bi
      frontal bone flap that is left floating posteriorly was performed to increase the
      cranial volume. RESULTS: All patients were cured. This technique increases the
      volume of the skull favoring the expansion of the brain and allows good
      cosmetical results. No perioperative complications were reported. DISCUSSION: The
      fact that the brain has a more appropriate volume allows the disappearance of the
      clinical symptomatology related to the split ventricle syndrome. The advantage is
      the respect of the fronto-orbital shape in children and adults with the same
      results of the classic frontal advancement in terms of volume expansion. The
      study of cerebral blood flow confirms the increase of the cerebral blood
      perfusion and the improvement of the regional cerebral blood flow in borderline
      regions. We preconize, for the treatment of slit ventricle syndrome, the bi
      frontal split technique in children and adults for its efficacy, the low rate of
      complications and the respect of aesthetical constraints.

PMID- 26205064
TI  - Population regulation in Gyrodactylus salaris - Atlantic salmon (Salmo salar L.)
      interactions: testing the paradigm.
AB  - BACKGROUND: Gyrodactylus salaris is a directly transmitted ectoparasite that
      reproduces in situ on its fish host. Wild Norwegian (East Atlantic) salmon stocks
      are thought to be especially susceptible to the parasite due to lack of co
      adaptation, contrary to Baltic salmon stocks. This study i) identifies whether
      time- and density-dependent mechanisms in gyrodactylid population growth exist in
      G. salaris-Atlantic salmon interactions and ii) based on differences between
      Norwegian and Baltic stocks, determines whether the 'Atlantic susceptible, Baltic
      resistant' paradigm holds as an example of local adaptation. METHODS: A total of
      18 datasets of G. salaris population growth on individually isolated Atlantic
      salmon (12 different stocks) infected with three parasite strains were re
      analysed using a Bayesian approach. Datasets included over 2000 observations of
      388 individual fish. RESULTS: The best fitting model of population growth was
      time-limited; parasite population growth rate declined consistently from the
      beginning of infection. We found no evidence of exponential population growth in
      any dataset. In some stocks, a density dependence in the size of the initial
      inoculum limited the maximum rate of parasite population growth. There is no
      evidence to support the hypothesis that all Norwegian and Scottish Atlantic
      salmon stocks are equally susceptible to G. salaris, while Baltic stocks control
      and limit infections due to co-evolution. Northern and Western Norwegian as well
      as the Scottish Shin stocks, support higher initial parasite population growth
      rates than Baltic, South-eastern Norwegian, or the Scottish Conon stocks, and
      several Norwegian stocks tested (Akerselva, Altaelva, Lierelva, Numedalslagen),
      and the Scottish stocks (i.e. Conon, Shin), were able to limit infections after
      40-50 days. No significant differences in performance of the three parasite
      strains (Batnfjordselva, Figga, and Lierelva), or the two parasite mitochondrial
      haplotypes (A and F) were observed. CONCLUSIONS: Our study shows a spectrum of
      growth rates, with some fish of the South-eastern Norwegian stocks sustaining
      parasite population growth rates overlapping those seen on Baltic Neva and
      Indalsalv stocks. This observation is inconsistent with the 'Baltic-resistant,
      Atlantic-susceptible' hypothesis, but suggests heterogeneity, perhaps linked to
      other host resistance genes driven by selection for local disease syndromes.

PMID- 26205065
TI  - Assessment of angiogenesis modulators in pregnant women with pre-eclampsia: a
      case-control study.
AB  - PURPOSE: This study aimed to evaluate the serum concentration of factors
      associated with placental angiogenesis in pre-eclamptic and normotensive pregnant
      women. METHODS: This was a prospective, cross-sectional, case-control study in
      which the pro-angiogenic factors PlGF, VEGF and IL-10, and the anti-angiogenic
      factors IL-6, IL-17 and TNF-alpha of 55 pregnant women (31 with pre-eclampsia-PE
      and 24 normotensive), with gestational age >=20 weeks, were measured in maternal
      blood through the enzyme-linked immunosorbent assay (ELISA). The Mann-Whitney and
      Kruskal-Wallis tests were used for comparison between groups. RESULTS: Serum PIGF
      was reduced in the group of pregnant women with PE when compared with the
      normotensive women (493.2 +/- 55.1 pg/mL vs. 4.4 +/- 26.5 pg/mL; p < 0.001).
      There was no significant difference in PlGF levels in the pre-eclamptic pregnant
      women in relation to gestational age or proteinuria levels (p > 0.05). The serum
      levels of VEGF, IL-17, IL-10 and TNF-alpha were lower in the pregnant women with
      PE when compared with their normotensive peers, while the IL-6 levels were
      higher; however, this difference was not statistically significant (p > 0.05).
      CONCLUSION: Serum PlGF levels were reduced in the pregnant women with PE and were
      unrelated to disease severity. Serum levels of VEGF, IL-17, IL-10 and TNF-alpha
      were reduced in the pre-eclamptic pregnant women when compared with their
      normotensive peers, without statistically significant differences.

PMID- 26205066
TI  - Validity of self-reported periodontal questions in a New Zealand cohort.
AB  - OBJECTIVE: This study aims to assess the validity of four self-reported questions
      for measuring periodontitis in a birth cohort. METHODS: Full-mouth periodontal
      examinations (three sites/tooth) were undertaken at age 38 in a complete birth
      cohort born in 1972/1973 in New Zealand. Four self-reported periodontal screening
      questions were included ("Do you think you have gum disease"; "Has a dental
      professional ever told you that you have lost bone around your teeth"; "Have you
      ever had scaling, root planing, surgery, or other treatment for gum disease" and
      "Have you ever had any teeth that have become loose by themselves without some
      injury"), and the sensitivity and specificity of those self-reported items were
      calculated for individual questions and using a multivariable binary logistic
      regression model. Generalised linear models were used to compare relative risks
      for periodontitis and smoking, using the (a) clinical measures and (b) self
      reported questions. RESULTS: Among the 895 who had periodontal examinations, the
      prevalence of periodontitis was 43.7, 22.8 and 12.0 %, respectively, for one or
      more sites with >=4, >=5 and >=6 mm clinical attachment loss (AL). The
      specificity of the four self-reported questions was high (82-94 %), but the
      sensitivity was low for all, except the question: "Do you think you have gum
      disease". The four questions' highest combined sensitivity + specificity value
      was 1.33 for one or more sites with >=4 mm AL, with the area under the receiver
      operating characteristic (ROC) curve being greatest for one or more sites with
      >=6 mm AL, at 0.84. For the smoking-periodontitis association, the estimates of
      relative risk for periodontitis among smokers were as follows: (a) 1.81, 2.88 and
      5.79, respectively, clinically determined to have one or more sites with >=4, >=5
      and >=6 mm AL and (b) 2.19, 2.17, 1.23 and 1.89, respectively, for the four self
      reported questions. CONCLUSION: The four self-reported periodontal screening
      questions performed adequately in identifying clinically determined periodontal
      disease, and they showed moderate validity when used together as a set. However,
      the strength of the association between smoking and periodontitis was
      underestimated when they were used instead of clinically determined periodontal
      disease. CLINICAL RELEVANCE: These findings suggest that clinical examinations
      remain to be the desired approach for periodontal surveys, but where resource
      constraints preclude those, self-reported methods can provide useful information;
      after all, some periodontal information is better than none at all.

PMID- 26205068
TI  - Daxx and TCF4 interaction links to oral squamous cell carcinoma growth by
      promoting cell cycle progression via induction of cyclin D1 expression.
AB  - OBJECTIVES: Death domain-associated protein (Daxx) has been recently implicated
      as a positive factor in ovarian cancer and prostate cancer, but the role of Daxx
      in oral squamous cell carcinoma (OSCC) has never been addressed. Herein, we
      investigate the expression and function of Daxx in OSCC. MATERIALS AND METHODS:
      RT-quantitative PCR, Western blotting, and immunohistochemistry were used to
      evaluation of the expression of Daxx in human OSCC cell lines and clinical
      surgical specimens. Short hairpin RNA targeting Daxx was transduced by lentivirus
      infection to knockdown the expression of Daxx in SAS and SCC25 cell lines, and
      the influence of this knockdown was evaluated by analyzing the growth and the
      cell cycle in transduced cells. Immunoprecipitation and sequential chromatin
      immunoprecipitation-quantitative PCR were used to analyze the associations
      between Daxx, TCF4, and cyclin D1 promoter. Xenograft tumor model was used to
      evaluate the in vivo tumorigenicity of Daxx in OSCC. RESULTS: Daxx mRNA and
      protein expression are elevated in several OSCC cell lines and human OSCC samples
      in comparison to those in normal tissue. We further find that depletion of Daxx
      decreases OSCC cell growth activity through G1 cell cycle arrest. Daxx silencing
      reduces cyclin D1 expression via a Daxx-TCF4 interaction, whereas the Daxx
      depletion-mediated G1 arrest can be relieved by ectopic expression of cyclin D1.
      Moreover, we show that in OSCC clinical samples, the expression of Daxx is
      significantly correlated with that of cyclin D1. CONCLUSION: Our data demonstrate
      the importance of Daxx in regulation of cyclin D1 expression and provide the
      first evidence that Daxx exhibits tumor-promoting activity in OSCC. CLINICAL
      RELEVANCE: Daxx plays an important role in malignant transformation of OSCC and
      may serves as a target for cancer prevention and treatment.

PMID- 26205067
TI  - Immediate tooth replantation in rats: effect of systemic antibiotic therapy with
      amoxicillin and tetracycline.
AB  - OBJECTIVES: The aim of this study was to evaluate the influence of systemic
      administration of antibiotics (amoxicillin and tetracycline) at the different
      phases of the repair process (7, 15, 30 days) in immediate rat tooth
      replantation. MATERIALS AND METHODS: Ninety rats had their incisors extracted and
      stored in saline for 5 min. Next, the teeth were replanted, and the animals were
      assigned to three groups according to the antibiotic administered by oral gavage:
      control group, amoxycillin group, and tetracycline group. Euthanasia was
      performed at 7, 15, and 30 days after replantation. RESULTS: Regardless of the
      evaluation period, the connective tissue underlying the epithelial attachment and
      the periodontal ligament showed statistically significant difference relative to
      the acute inflammatory infiltrate, which was more intense in the control group
      followed by the tetracycline group. CONCLUSION: These results point to the fact
      that systemic antibiotic therapy (SAT) in immediate tooth replantation is
      beneficial to pulpal and periodontal ligament repair and that amoxycillin is an
      excellent option. CLINICAL RELEVANCE: There is a lack of randomized studies
      assessing how the use of systemic antibiotics could influence tooth healing after
      immediate replantation.

PMID- 26205069
TI  - Evaluation of cytotoxic activity of titanocene difluorides and determination of
      their mechanism of action in ovarian cancer cells.
AB  - BACKGROUND: Ovarian cancer is the seventh-most common cancer amongst women and
      the most deadly gynecologic cancer. Cisplatin based drugs are used in first line
      therapy, but resistance represents a major obstacle for successful treatment. In
      this study, we investigated the anticancer effects and mechanism of action of
      three titanocene difluorides, two bearing a pendant carbohydrate moiety (alpha-D
      ribofuranos-5-yl) on their periphery and one without any substitution. RESULTS:
      The efficacy of these compounds on ovarian cancer cell lines was evaluated in
      relation to their particular chemical structure and compared with cisplatin as
      the most common treatment modality for this type of cancer. The typical mechanism
      of cisplatin action involves DNA damage, activation of p53 protein and induction
      of cell death, as previously described for titanium ions. Nevertheless, our data
      indicate that the effect of titanocene difluoride derivatives is mediated via the
      endoplasmic reticulum stress pathway and autophagy. CONCLUSION: We anticipate
      that the presence of substituents on cyclopentadienyl ring(s) might play an
      important role in modulation of the activity of particular compounds. Titanocene
      difluorides exert comparable cytotoxic activity as cisplatin and are more
      efficient in cisplatin-resistant cell lines. Our results suggest potential
      utilization of these compounds especially in the treatment of cisplatin-resistant
      tumor cells.

PMID- 26205070
TI  - Heat Stress Illness Emergency Department Visits in National Environmental Public
      Health Tracking States, 2005-2010.
AB  - Variability of heat stress illness (HSI) by urbanicity and climate region has
      rarely been considered in previous HSI studies. We investigated temporal and
      geographic trends in HSI emergency department (ED) visits in CDC Environmental
      Public Health Tracking Network (Tracking) states for 2005-2010. We obtained
      county-level HSI ED visit data for 14 Tracking states. We used the National
      Center for Health Statistics Urban-Rural Classification Scheme to categorize
      counties by urbanicity as (1) large central metropolitan (LCM), (2) large fringe
      metropolitan, (3) small-medium metropolitan, or (4) nonmetropolitan (NM). We also
      assigned counties to one of six US climate regions. Negative binomial regression
      was used to examine trends in HSI ED visits over time across all counties and by
      urbanicity for each climate region, adjusting for pertinent variables. During
      2005-2010, there were 98,462 HSI ED visits in the 14 states. ED visits for HSI
      decreased 3.0% (p < 0.01) per year. Age-adjusted incidence rates of HSI ED visits
      increased from most urban to most rural. Overall, ED visits were significantly
      higher for NM areas (IRR = 1.41, p < 0.01) than for LCM areas. The same pattern
      was observed in all six climate regions; compared with LCM, NM areas had from 14
      to 90% more ED visits for HSI. These findings of significantly increased HSI ED
      visit rates in more rural settings suggest a need to consider HSI ED visit
      variability by county urbanicity and climate region when designing and
      implementing local HSI preventive measures and interventions.

PMID- 26205071
TI  - Borders in Education and Living- a Case of Trench Warfare.
AB  - In this paper the notion of border will be examined in a cultural life course
      perspective. I will investigate borders as psycho-cultural constructions created
      to enable and control meaning-making in the intersection between subjects
      engagements and concerns and collectively constructed and guiding meanings. An
      empirical analysis of one boy's life course in and between home, school and a
      Leisure Time Activity Center in the years 1st to 3rd grade demonstrates a
      systemic construction of borders involving him, his teachers and his parents and
      renders the boy to choose between becoming an engaged pupil or a dedicated son.
      As such, the analysis can illuminate processes of school - home interactions that
      work opposite of what is intended and become detrimental to children's life. In a
      cultural life course perspective borders show how life is maintained as
      meaningful and not only guide the present living but also serve as directional
      guides into the future. 

PMID- 26205073
TI  - Effects of clay minerals and organic matter in formulated sediments on the
      bioavailability of sediment-associated uranium to the freshwater midge,
      Chironomus dilutus.
AB  - It is well established that bioavailability influences metal toxicity in aquatic
      ecosystems. However, the factors and mechanisms that influence uranium (U)
      bioavailability and toxicity in sediment have not been thoroughly evaluated,
      despite evidence that suggests different sediment components can influence the
      sorption and interaction of some metals. Given that dissolved U is generally
      accepted as being the primary bioavailable fraction of U, it is hypothesized that
      adsorption and interaction of U with different sediment components will influence
      the bioavailability of U in sediment. We investigated the effects of key sediment
      physicochemical properties on the bioavailability of U to a model freshwater
      benthic invertebrate, Chironomus dilutus. Several 10-day spiked sediment
      bioaccumulation experiments were performed, exposing C. dilutus larvae to a
      variety of formulated sediments spiked with different concentrations of U (5, 50
      and/or 200 mg U/kg d.w.). Mean accumulation of U in C. dilutus larvae decreased
      significantly from 1195 to 10 mg U/kg d.w. as kaolin clay content increased from
      0% to 60% in sediment spiked with 50 mg U/kg d.w. Similarly, higher organic
      matter content also resulted in a significant reduction of U bioaccumulation in
      C. dilutus larvae, indicating a reduction in U bioavailability. Concentrations of
      U in both the overlying water and sediment pore water displayed a strong positive
      relationship to U bioaccumulation in C. dilutus larvae (r(2) = 0.77, p<0.001 and
      r(2) = 0.57, p < 0.001, respectively) for all experiments, while total U
      concentrations in the sediment had a poor relationship to U bioaccumulation (r(2)
      = 0.10, p = 0.028). Results from this research confirm that sediment clay and
      organic matter content play a significant role in altering U bioavailability,
      which is important in informing risk assessments of U contaminated sites and in
      the development of site-specific sediment quality guidelines for U.

PMID- 26205072
TI  - Pseudomonas syringae enhances herbivory by suppressing the reactive oxygen burst
      in Arabidopsis.
AB  - Plant-herbivore interactions have evolved in the presence of plant-colonizing
      microbes. These microbes can have important third-party effects on herbivore
      ecology, as exemplified by drosophilid flies that evolved from ancestors feeding
      on plant-associated microbes. Leaf-mining flies in the genus Scaptomyza, which is
      nested within the paraphyletic genus Drosophila, show strong associations with
      bacteria in the genus Pseudomonas, including Pseudomonas syringae. Adult females
      are capable of vectoring these bacteria between plants and larvae show a
      preference for feeding on P. syringae-infected leaves. Here we show that
      Scaptomyza flava larvae can also vector P. syringae to and from feeding sites,
      and that they not only feed more, but also develop faster on plants previously
      infected with P. syringae. Our genetic and physiological data show that P.
      syringae enhances S. flava feeding on infected plants at least in part by
      suppressing anti-herbivore defenses mediated by reactive oxygen species.

PMID- 26205074
TI  - Frequency and topography of cerebral microbleeds in dementia with Lewy bodies
      compared to Alzheimer's disease.
AB  - AIM: To determine the frequency and topographic distribution of cerebral
      microbleeds (CMBs) in dementia with Lewy bodies (DLB) in comparison to CMBs in
      Alzheimer disease dementia (AD). METHODS: Consecutive probable DLB (n = 23)
      patients who underwent 3-T T2* weighted gradient-recalled-echo MRI, and age and
      gender matched probable Alzheimer's disease patients (n = 46) were compared for
      the frequency and location of CMBs. RESULTS: The frequency of one or more CMBs
      was similar among patients with DLB (30%) and AD (24%). Highest densities of CMBs
      were found in the occipital lobes of patients with both DLB and AD. Patients with
      AD had greater densities of CMBs in the parietal, temporal lobes and
      infratentorial regions compared to DLB (p < 0.05). CONCLUSION: CMBs are as common
      in patients with DLB as in patients with AD, with highest densities observed in
      the occipital lobes, suggesting common pathophysiologic mechanisms underlying
      CMBs in both diseases.

PMID- 26205075
TI  - (18)F-labeled rhodamines as potential myocardial perfusion agents: comparison of
      pharmacokinetic properties of several rhodamines.
AB  - INTRODUCTION: We recently reported the development of the [(18)F]fluorodiethylene
      glycol ester of rhodamine B as a potential positron emission tomography (PET)
      tracer for myocardial perfusion imaging (MPI). This compound was developed by
      optimizing the ester moiety on the rhodamine B core, and its pharmacokinetic
      properties were found to be superior to those of the prototype ethyl ester. The
      goal of the present study was to optimize the rhodamine core while retaining the
      fluorodiethyleneglycol ester prosthetic group. METHODS: A series of different
      rhodamine cores (rhodamine 6G, rhodamine 101, and tetramethylrhodamine) were
      labeled with (18)F using the corresponding rhodamine lactones as the precursors
      and [(18)F]fluorodiethylene glycol ester as the prosthetic group. The compounds
      were purified by semipreparative HPLC, and their biodistribution was measured in
      rats. Additionally, the uptake of the compounds was evaluated in isolated rat
      cardiomyocytes. RESULTS: As was the case with the different prosthetic groups, we
      found that the rhodamine core has a significant effect on the in vitro and in
      vivo properties of this series of compounds. Of the rhodamines evaluated to date,
      the pharmacologic properties of the (18)F-labeled diethylene glycol ester of
      rhodamine 6G are superior to those of the (18)F-labeled diethylene glycol esters
      of rhodamine B, rhodamine 101, and tetramethylrhodamine. As with (18)F-labeled
      rhodamine B, [(18)F]rhodamine 6G was observed to localize in the mitochondria of
      isolated rat cardiomyocytes. CONCLUSIONS: Based on these results, the (18)F
      labeled diethylene glycol ester of rhodamine 6G is the most promising potential
      PET MPI radiopharmaceutical of those that have evaluated to date, and we are now
      preparing to carry out first-in-human clinical studies with this compound.

PMID- 26205076
TI  - Radiopharmacological evaluation of (18)F-labeled phosphatidylserine-binding
      peptides for molecular imaging of apoptosis.
AB  - INTRODUCTION: Radiolabeled phosphatidylserine (PS)-binding peptides represent an
      innovative strategy for molecular imaging of apoptosis with positron emission
      tomography (PET). The goal of this study was the radiopharmacological evaluation
      of radiolabeled peptides for their binding to PS on apoptotic cancer cells,
      involving metabolic stability, cellular uptake, biodistribution, and dynamic PET
      imaging experiments. METHODS: Binding of peptides LIKKPF, PGDLSR, FBz-LIKKPF, FBz
      PGDLSR, FBAM-CLIKKPF and FBAM-CPGDLSR to PS was analyzed in a newly developed
      radiometric binding assay using (64)Cu-labeled wild-type annexin-V as
      radiotracer. Radiolabeling of most potent peptides with fluorine-18 was carried
      out with thiol-selective prosthetic group [(18)F]FBAM to give [(18)F]FBAM-CLIKKPF
      and [(18)F]FBAM-CPGDLSR. [(18)F]FBAM-labeled peptides were studied in
      camptothecin-induced apoptotic human T lymphocyte Jurkat cells, and in a murine
      EL4 tumor model of apoptosis using dynamic PET imaging and biodistribution.
      RESULTS: Peptides LIKKPF and PGDLSR inhibited binding of (64)Cu-labeled annexin-V
      to immobilized PS in the millimolar range (IC50 10-15 mM) compared to annexin-V
      (45 nM). Introduction of FBAM prosthetic group slightly increased inhibitory
      potencies (FBAM-CLIKKPF: IC50 = 1 mM; FBAM-CPGDLSR: IC50 = 6 mM). Radiolabeling
      succeeded in good radiochemical yields of 50-54% using a chemoselective
      alkylation reaction of peptides CLIKKPF and CPGDLSR with [(18)F]FBAM. In vivo
      metabolic stability studies in mice revealed 40-60% of intact peptides at 5 min
      p.i. decreasing to 25% for [(18)F]FBAM-CLIKKPF and less than 5% for [(18)F]FBAM
      CPGDLSR at 15 min p.i.. Cell binding of [(18)F]FBAM-CLIKKPF in drug-treated
      Jurkat cells was significantly higher compared to untreated cells, but this was
      not observed for [(18)F]FBAM-CPGDLSR. Dynamic PET imaging experiments showed that
      baseline uptake of [(18)F]FBAM-CLIKKPF in EL4 tumors was higher (SUV(5min) 0.46,
      SUV(60min) 0.13) compared to [(18)F]FBAM-CPGDLSR (SUV(5min) 0.16, SUV(60min)
      0.10). Drug-treated EL4 tumors did not show an increased uptake for both
      [(18)F]FBAM-labeled peptides. CONCLUSION: Although both (18)F-labeled peptides
      [(18)F]FBAM-CLIKKPF and [(18)F]FBAM-CPGDLSR showed higher binding to apoptotic
      Jurkat cells in vitro, their in vivo uptake profiles were not different in
      apoptotic EL4 tumors. This may explained by the relatively low potency of both
      compounds to compete with binding of (64)Cu-labeled annexin-V to PS. Overall the
      novel competitive radiometric PS-binding assay with (64)Cu-labeled annexin-V
      represents a versatile and very robust screening platform to analyze potential PS
      binding compounds in vitro. Further studies will be necessary to evaluate
      alternative peptide structures toward their use as PET radiotracers imaging
      apoptosis in vivo. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE:
      Development of peptide-based radiotracers for imaging apoptosis in vivo remains a
      significant challenge.

PMID- 26205078
TI  - The pandemic potential of avian influenza A(H7N9) virus: a review.
AB  - In March 2013 the first cases of human avian influenza A(H7N9) were reported to
      the World Health Organization. Since that time, over 650 cases have been
      reported. Infections are associated with considerable morbidity and mortality,
      particularly within certain demographic groups. This rapid increase in cases over
      a brief time period is alarming and has raised concerns about the pandemic
      potential of the H7N9 virus. Three major factors influence the pandemic potential
      of an influenza virus: (1) its ability to cause human disease, (2) the immunity
      of the population to the virus, and (3) the transmission potential of the virus.
      This paper reviews what is currently known about each of these factors with
      respect to avian influenza A(H7N9). Currently, sustained human-to-human
      transmission of H7N9 has not been reported; however, population immunity to the
      virus is considered very low, and the virus has significant ability to cause
      human disease. Several statistical and geographical modelling studies have
      estimated and predicted the spread of the H7N9 virus in humans and avian species,
      and some have identified potential risk factors associated with disease
      transmission. Additionally, assessment tools have been developed to evaluate the
      pandemic potential of H7N9 and other influenza viruses. These tools could also
      hypothetically be used to monitor changes in the pandemic potential of a
      particular virus over time. 

PMID- 26205079
TI  - Asymptomatic malrotation: Diagnosis and surgical management: An American
      Pediatric Surgical Association outcomes and evidence based practice committee
      systematic review.
AB  - OBJECTIVE: Patients with malrotation, or an intestinal rotation abnormality
      (IRA), can experience serious adverse events. Increasingly, asymptomatic patients
      are being diagnosed with malrotation incidentally. Patients with symptomatic
      malrotation require surgery in an urgent or semiurgent manner to address their
      symptoms. The treatment of asymptomatic or incidentally discovered malrotation
      remains controversial. METHODS: Data were compiled from a broad search of
      Medline, Cochrane, Embase and Web of Science from January 1980 through January
      2013 for five questions regarding asymptomatic malrotation. RESULTS: There is
      minimal evidence to support screening asymptomatic patients. Consideration may be
      given to operate on asymptomatic patients who are younger in age, while
      observation may be appropriate in the older patient. If reliably diagnosed,
      atypical malrotation with a broad-based mesentery and malposition of the duodenum
      can be observed. Regarding diagnostic imaging, the standard of care for diagnosis
      remains the upper gastrointestinal contrast study (UGI), ultrasound may be useful
      for screening. A laparoscopic approach is safe for diagnosis and treatment of
      rotational abnormalities. Laparoscopy can aid in determining whether a patient
      has true malrotation with a narrow mesenteric stalk, has nonrotation and minimal
      risk for volvulus, or has atypical anatomy with malposition of the duodenum. It
      is reasonable to delay Ladd procedures until after palliation on patients with
      severe congenital heart disease. Observation can be considered with extensive
      education for family and caregivers and close clinical follow-up. CONCLUSIONS:
      There is a lack of quality data to guide the management of patients with
      asymptomatic malrotation. Multicenter and prospective data should be collected to
      better assess the risk profile for this complex group of patients. A
      multidisciplinary approach involving surgery, cardiology, critical care and the
      patient's caregivers can help guide a watchful waiting management plan in
      individual cases.

PMID- 26205080
TI  - Developmental succession of the microbiome of Culex mosquitoes.
AB  - BACKGROUND: The native microflora associated with mosquitoes have important roles
      in mosquito development and vector competence. Sequencing of bacterial V3 region
      from 16S rRNA genes across the developmental stages of Culex mosquitoes (early
      and late larval instars, pupae and adults) was used to test the hypothesis that
      bacteria found in the larval stage of Culex are transstadially transmitted to the
      adult stage, and to compare the microbiomes of field-collected versus laboratory
      reared mosquitoes. RESULTS: Beta diversity analysis revealed that bacterial
      community structure differed among three life stages (larvae, pupae and adults)
      of Culex tarsalis. Although only ~2% of the total number of bacterial OTUs were
      found in all stages, sequences from these OTUs accounted for nearly 82% of the
      total bacterial sequences recovered from all stages. Thorsellia
      (Gammaproteobacteria) was the most abundant bacterial taxon found across all
      developmental stages of field-collected Culex mosquitoes, but was rare in
      mosquitoes from laboratory-reared colonies. The proportion of Thorsellia
      sequences in the microbiomes of mosquito life stages varied ontogenetically with
      the greatest proportions recovered from the pupae of C. tarsalis and the lowest
      from newly emerged adults. The microbiome of field-collected late instar larvae
      was not influenced significantly by differences in the microbiota of the habitat
      due to habitat age or biopesticide treatments. The microbiome diversity was the
      greatest in the early instar larvae and the lowest in laboratory-reared
      mosquitoes. CONCLUSIONS: Bacterial communities in early instar C. tarsalis larvae
      were significantly more diverse when compared to late instar larvae, pupae and
      newly emerged adults. Some of the bacterial OTUs found in the early instar larvae
      were also found across developmental stages. Thorsellia dominated the bacterial
      communities in field-collected immature stages but occurred at much lower
      relative abundance in adults. Differences in microbiota observed in larval
      habitats did not influence bacterial community profiles of late instar larvae or
      adults. However, bacterial communities in laboratory-reared C. tarsalis larvae
      differed significantly from the field. Determining the role of Thorsellia in
      mosquitoes and its distribution across different species of mosquitoes warrants
      further investigation.

PMID- 26205081
TI  - Anti-B lymphocyte immunotherapy is associated with improvement of periodontal
      status in subjects with rheumatoid arthritis.
AB  - AIM: Rheumatoid arthritis (RA) and periodontitis present many similar features.
      The benefits of anti-B lymphocyte therapy (rituximab) on reducing tissue
      resorption in RA prompted us to assess its potential efficacy on the periodontal
      status of patients with RA treated with rituximab. MATERIALS AND METHODS:
      Periodontal status was assessed in 21 subjects with RA, divided into two groups:
      Group I consisted in 11 subjects assessed before their first infusion of
      rituximab and again 6 months later. Five of them were also assessed for up to 4
      years after their first rituximab infusion. The 10 subjects in group II had
      received more than two courses of two rituximab infusions at the time of
      periodontal assessment. RESULTS: Pocket depth and attachment loss were
      significantly decreased 6 months after treatment with rituximab in group I. The
      periodontal status of the five subjects from group I followed for up to 48 months
      after rituximab treatment was improved irrespective of the clinical parameter
      observed. Patients from group II had a better periodontal status than patients
      from group I before treatment with rituximab. CONCLUSIONS: Anti-B lymphocyte
      therapy could be beneficial to improve periodontitis suggesting a major role of B
      cells in this disease.

PMID- 26205082
TI  - A Neutralizing Antibody Assay Based on a Reporter of Antibody-Dependent Cell
      Mediated Cytotoxicity.
AB  - Benralizumab is a humanized anti-IL5 receptor alpha (IL5Ralpha) monoclonal
      antibody (mAb) with enhanced (afucosylation) antibody-dependent cell-mediated
      cytotoxicity (ADCC) function. An ADCC reporter cell-based neutralizing antibody
      (NAb) assay was developed and characterized to detect NAb against benralizumab in
      human serum to support the clinical development of benralizumab. The optimal
      ratio of target cells to effector cells was 3:1. Neither parental benralizumab
      (fucosylated) nor benralizumab Fab resulted in ADCC activity, confirming the
      requirement for ADCC activity in the NAb assay. The serum tolerance of the cells
      was determined to be 2.5%. The cut point derived from normal and asthma serum
      samples was comparable. The effective range of benralizumab was determined, and
      35 ng/mL [80% maximal effective concentration (EC80)] was chosen as the standard
      concentration to run in the assessment of NAb. An affinity purified goat anti
      benralizumab polyclonal idiotype antibody preparation was shown to have NAb since
      it inhibited ADCC activity in a dose-dependent fashion. The low endogenous
      concentrations of IL5 and soluble IL5 receptor (sIL5R) did not demonstrate to
      interfere with the assay. The estimated assay sensitivities at the cut point were
      1.02 and 1.10 MUg/mL as determined by the surrogate neutralizing goat polyclonal
      and mouse monoclonal anti-drug antibody (ADA) controls, respectively. The assay
      can detect NAb (at 2.5 MUg/mL) in the presence of 0.78 MUg/mL benralizumab. The
      assay was not susceptible to non-specific matrix effects. This study provides an
      approach and feasibility of developing an ADCC cell-based NAb assay to support
      biopharmaceuticals with an ADCC function. 

PMID- 26205083
TI  - Duplex Doppler Imaging of Dialysis Fistulae and Grafts.
AB  - Arteriovenous fistulae and grafts for hemodialysis access are a lifeline in
      patients with end-stage renal disease. A significant cause of morbidity and
      mortality in this population is dialysis access dysfunction. Duplex ultrasound
      imaging is an excellent modality to evaluate arteriovenous fistulae and grafts,
      the 2 main types of long-term hemodialysis access. This review provides a
      detailed Doppler ultrasound protocol for evaluation of fistulae or grafts to
      familiarize imagers with their normal appearance, highlighting common dialysis
      access complications.

PMID- 26205084
TI  - Runx1 repression by histone deacetylation is critical for Setbp1-induced mouse
      myeloid leukemia development.
AB  - Abnormal activation of SETBP1 through overexpression or missense mutations is
      highly recurrent in various myeloid malignancies; however, it is unclear whether
      such activation alone is able to induce leukemia development. Here we show that
      Setbp1 overexpression in mouse bone marrow progenitors through retroviral
      transduction is capable of initiating leukemia development in irradiated
      recipient mice. Before leukemic transformation, Setbp1 overexpression
      significantly enhances the self-renewal of hematopoietic stem cells (HSCs) and
      expands granulocyte macrophage progenitors (GMPs). Interestingly, Setbp1
      overexpression also causes transcriptional repression of critical hematopoiesis
      regulator gene Runx1 and this effect is crucial for Setbp1-induced
      transformation. Runx1 repression is induced by Setbp1-mediated recruitment of a
      nucleosome remodeling deacetylase (NuRD) complex to Runx1 promoters and can be
      reversed by treatment with histone deacetylase (HDAC) inhibitors Entinostat and
      Vorinostat. Moreover, treatment with these inhibitors caused efficient
      differentiation of Setbp1 activation-induced leukemia cells in vitro, and
      significantly extended the survival of mice transplanted with such leukemias,
      suggesting that HDAC inhibition could be an effective strategy for treating
      myeloid malignancies with SETBP1 activation. 

PMID- 26205085
TI  - Mitochondrial thioredoxin reductase regulates major cytotoxicity pathways of
      proteasome inhibitors in multiple myeloma cells.
AB  - It is generally accepted that intracellular oxidative stress induced by
      proteasome inhibitors is a byproduct of endoplasmic reticulum (ER) stress. Here
      we report a mechanism underlying the ability of proteasome inhibitors bortezomib
      (BTZ) and carfilzomib (CFZ) to directly induce oxidative and ER stresses in
      multiple myeloma (MM) cells via transcriptional repression of a gene encoding
      mitochondrial thioredoxin reductase (TXNRD2). TXNRD2 is critical for maintenance
      of intracellular red-ox status and detoxification of reactive oxygen species.
      Depletion of TXNRD2 to the levels detected in BTZ- or CFZ-treated cells causes
      oxidative stress, ER stress and death similar to those induced by proteasome
      inhibitors. Reciprocally, restoration of near-wildtype TXNRD2 amounts in MM cells
      treated with proteasome inhibitors reduces oxidative stress, ER stress and cell
      death by ~46%, ~35% and ~50%, respectively, compared with cells with unrestored
      TXNRD2 levels. Moreover, cells from three MM cell lines selected for resistance
      to BTZ demonstrate elevated levels of TXNRD2, indirectly confirming its
      functional role in BTZ resistance. Accordingly, ectopic expression of TXNRD2 in
      MM cell xenografts in immunocompromised mice blunts therapeutic effects of BTZ.
      Our data identify TXNRD2 as a potentially clinically relevant target, inhibition
      of which is critical for proteasome inhibitor-dependent cytotoxicity, oxidative
      stress and ER stress. 

PMID- 26205087
TI  - Treatment of eccrine porocarcinoma with Mohs micrographic surgery: a cases series
      and literature review.
AB  - BACKGROUND: Eccrine porocarcinoma (EPC) is a rare malignant tumor of the eccrine
      sweat gland. It is a potentially fatal neoplasm that is locally aggressive and
      commonly recurs. Wide surgical excision has traditionally been the treatment of
      choice and is curative in approximately 70-80% of cases. The disease is
      metastatic to lymph nodes and distant sites in 20% and 10% of cases,
      respectively. Metastatic EPC has not shown any great response to adjuvant
      chemotherapy or radiation. OBJECTIVE: The purpose of this study was to evaluate
      the efficacy of Mohs micrographic surgery (MMS) for EPC as an alternative to wide
      local excision. METHODS: Five patients diagnosed with EPS between 2011 and 2014
      at the University of Louisville and treated with MMS were studied. Recurrence
      free periods subsequent to the treatment of EPC with MMS were measured. RESULTS:
      The five patients with EPC treated by MMS remained recurrence-free for a mean of
      11 months (range: 2-26 months). CONCLUSIONS: Mohs micrographic surgery is a
      highly effective treatment for EPC. Given the high rate of recurrence, propensity
      for lymph node metastases, and the often ineffective options for treating
      advanced disease, MMS should be considered in the treatment of all cases of EPC.

PMID- 26205086
TI  - Beneficial effects of a ketamine/atropine combination in soman-poisoned rats
      under a neutral thermal environment.
AB  - Exposure to organophosphorus (OP) compounds, such as pesticides and the chemical
      warfare agents (soman and sarin), respectively represents a major health problem
      and a threat for civilian and military communities. OP poisoning may induce
      seizures, status epilepticus and even brain lesions if untreated. We recently
      proved that a combination of atropine sulfate and ketamine, a glutamatergic
      antagonist, was effective as an anticonvulsant and neuroprotectant in mice and
      guinea-pigs exposed to soman. Since OP exposure may also occur in conditions of
      heat strain due to climate, wearing of protective gears or physical exercise, we
      previously demonstrated that ketamine/atropine association may be used in a hot
      environment without detrimental effects. In the present study, we assess soman
      toxicity and evaluate the effects of the ketamine/atropine combination on soman
      toxicity in a warm thermoneutral environment. Male Wistar rats, exposed to 31
      degrees C (easily reached under protective equipments), were intoxicated by soman
      and treated with an anesthetic dose of ketamine combined with atropine sulfate.
      Body core temperature and spontaneous locomotor activity were continuously
      monitored using telemetry. At the end of the warm exposure, blood chemistry and
      brain mRNA expression of some specific genes were measured. In soman-intoxicated
      animals, metabolic and genic modifications were related to convulsions rather
      than to soman intoxication by itself. In the warm environment, ketamine/atropine
      combination did not produce any side-effect on the assessed variables.
      Furthermore, the ketamine/atropine combination exhibited beneficial therapeutic
      effects on soman-intoxicated rats such as a limitation of convulsion-induced
      hyperthermia and of the increase in some blood chemistry markers. 

PMID- 26205088
TI  - Anteroposterior Laxity After Bicruciate-Retaining Total Knee Arthroplasty Is
      Closer to the Native Knee Than ACL-Resecting TKA: A Biomechanical Cadaver Study.
AB  - The purpose of this study was to examine whether a bicruciate retaining (BCR) TKA
      would yield anteroposterior (AP) laxity closer to the native knee than a
      posterior cruciate ligament retaining (CR) TKA. A BCR TKA was designed and
      compared to CR TKA and the native knee using cadaver specimens. AP laxity with
      the CR TKA was greater than the native knee (P=0.006) and BCR TKA (P=0.039), but
      no difference was found between the BCR TKA and the native knee. No significant
      differences were found in rotations between the prostheses and the native knee.
      BCR TKA was shown to be surgically feasible, reduced AP laxity versus CR TKA, and
      may improve knee stability without using conforming geometry in the implant
      design. 

PMID- 26205089
TI  - Readmission and Complications for Catheter and Injection Femoral Nerve Block
      Administration After Total Knee Arthroplasty in the Medicare Population.
AB  - There is general agreement that femoral nerve blocks (FNB) provide adequate
      immediate postoperative analgesia after total knee arthroplasty (TKA), although
      the effect of this technique on hospital readmission and other complications has
      not been quantified in a large sample. The Medicare 5% sample was used to
      identify TKA patients who were grouped according to postoperative FNB
      administration: FNB via injection; FNB via pain pump; and no FNB. Multivariate
      Cox regressions were used to evaluate risk factors for the postoperative
      outcomes. Both FNB groups were associated with a lower risk of readmission (30,
      90 and 365 days, P<0.001). Future clinical studies may help elucidate whether the
      lower hospital readmissions may be associated with more effective pain control
      with the use of FNB.

PMID- 26205090
TI  - [Plasma IL-18 levels are related to insulin and are modulated by IL-18 gene
      polymorphisms].
AB  - INTRODUCTION: Atherosclerosis is an inflammatory chronic disease influenced by
      multiple factors. Different prospective studies have shown that plasmatic levels
      of inflammatory markers were related to atherosclerosis and cardiovascular
      disease. OBJECTIVE: To evaluate whether plasmatic levels of interleukin 18 (IL
      18) are modulated by SNPs (single nucleotide polymorphisms) of the IL 18 gene and
      its possible association with insulin levels and other cardiovascular risk
      factors. METHODS: 746 individuals were studied for a period of two years by
      opportunistic selection in the metropolitan area of Valencia. Parameters of lipid
      and glucose metabolism were analyzed by standard methodology. IL-18 was measured
      by ELISA. RESULTS: Individuals with insulin resistance showed significant higher
      levels of IL-18. IL 18 was significantly correlated with insulin levels and other
      cardiovascular risk factors. The CC genotype of the rs1834481 SNP was
      significantly associated with lower levels of IL-18. However, the GG genotype of
      the rs7559479 was associated with significant higher levels of IL-18. CONCLUSION:
      IL-18 is associated with insulin resistance and other cardiovascular risk
      factors, being those levels genetically regulated.

PMID- 26205091
TI  - Immunoregulatory effects of sirolimus vs. tacrolimus treatment in kidney
      allograft recipients.
AB  - The difference in immunoregulatory effects between sirolimus and tacrolimus on
      kidney transplantation remains unclear. In this study, a total of 18 living-donor
      related kidney transplant recipients received sirolimus (n=8) or tacrolimus
      (n=10) treatment. Kidney function, acute rejection, peripheral blood
      CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs), CD19(+)CD5(+)CD1d(+) regulatory
      B cells (Bregs), and panel reactivity antibody were analyzed after one and three
      years. Th1/2 cell polarization was also determined at one year. The proportion of
      Tregs in the recipients receiving tacrolimus significantly decreased to 3.69% and
      2.49% at one and three years, respectively, compared to 6.59% in controls,
      whereas the proportion in the recipients receiving sirolimus remained at 6.67%
      and 5.66%, respectively. However, no differences in kidney function, acute
      rejection, proportion of Bregs, panel reactivity antibody, or the frequencies of
      Th1/2 cells were identified. In conclusion, unlike tacrolimus, sirolimus
      maintains the proportion of Tregs in kidney transplant recipients. 

PMID- 26205092
TI  - Gynecologic age is an important risk factor for obstetric and perinatal outcomes
      in adolescent pregnancies.
AB  - BACKGROUND: Adolescent pregnancy is an important public health problem.
      Physiological maturity affects obstetric and perinatal outcomes. Almost all
      assessments of adolescent pregnancies are based on chronological age. Gynecologic
      age (GA) is defined as age in years at conception minus age at menarche and it is
      an indicator of physiological maturity. AIM: To compare obstetric and perinatal
      outcomes between adult and adolescent pregnancies as categorized according to GA.
      METHODS: In this retrospective study, 233 adolescent pregnant women were divided
      into two groups based on GA<=3 years (101 women) and GA>3 years (132 women).
      Their obstetric and perinatal results were compared with 202 adult pregnancies
      who gave birth in the same period. FINDINGS: Gestational age at delivery, APGAR
      scores, birth weight, and incidence of preterm birth, admission to neonatal
      intensive care unit (NICU), intrauterine growth restriction, low birth weight,
      and premature rupture of membranes were significantly different between the study
      groups. Compared to adolescent pregnancies with GA>3 years, adolescent
      pregnancies with GA<=3 years had significantly lower birth weight, gestational
      age, APGAR scores, and significantly higher incidence of intrauterine growth
      restriction, low birth weight and admission to NICU. CONCLUSION: Low GA is
      associated with an increased rate of obstetric and perinatal complications in
      adolescent pregnancies. Although the main aim is the prevention of adolescent
      pregnancies, a detailed evaluation of such pregnancies including determination of
      the gynecological age together with a multidisciplinary approach may decrease
      potential complications.

PMID- 26205093
TI  - Collagens and proteoglycans of the cornea: importance in transparency and visual
      disorders.
AB  - The cornea represents the external part of the eye and consists of an epithelium,
      a stroma and an endothelium. Due to its curvature and transparency this structure
      makes up approximately 70% of the total refractive power of the eye. This
      function is partly made possible by the particular organization of the collagen
      extracellular matrix contained in the corneal stroma that allows a constant
      refractive power. The maintenance of such an organization involves other
      molecules such as type V collagen, FACITs (fibril-associated collagens with
      interrupted triple helices) and SLRPs (small leucine-rich proteoglycans). These
      components play crucial roles in the preservation of the correct organization and
      function of the cornea since their absence or modification leads to abnormalities
      such as corneal opacities. Thus, the aim of this review is to describe the
      different corneal collagens and proteoglycans by highlighting their importance in
      corneal transparency as well as their implication in corneal visual disorders.

PMID- 26205094
TI  - A comprehensive, genome-wide analysis of autophagy-related genes identified in
      tobacco suggests a central role of autophagy in plant response to various
      environmental cues.
AB  - Autophagy is an evolutionarily conserved mechanism in both animals and plants,
      which has been shown to be involved in various essential developmental processes
      in plants. Nicotiana tabacum is considered to be an ideal model plant and has
      been widely used for the study of the roles of autophagy in the processes of
      plant development and in the response to various stresses. However, only a few
      autophagy-related genes (ATGs) have been identified in tobacco up to now. Here,
      we identified 30 ATGs belonging to 16 different groups in tobacco through a
      genome-wide survey. Comprehensive expression profile analysis reveals an abroad
      expression pattern of these ATGs, which could be detected in all tissues tested
      under normal growth conditions. Our series tests further reveal that majority of
      ATGs are sensitive and responsive to different stresses including nutrient
      starvation, plant hormones, heavy metal and other abiotic stresses, suggesting a
      central role of autophagy, likely as an effector, in plant response to various
      environmental cues. This work offers a detailed survey of all ATGs in tobacco and
      also suggests manifold functions of autophagy in both normal plant growth and
      plant response to environmental stresses. 

PMID- 26205095
TI  - Technical Modifications to Prevent Massive Hemothorax Following Sternal Plating.
AB  - We report two cases of life-threatening massive hemothorax after titanium plate
      fixation. We propose a modification of this technique using smaller plates that
      span the sternal bone but do not encroach upon the cartilage of the ribcage.

PMID- 26205096
TI  - alpha5-nAChR modulates nicotine-induced cell migration and invasion in A549 lung
      cancer cells.
AB  - Cigarette smoking is the most important risk factor in the development of human
      lung cancer. Nicotine, the major component in tobacco, not only contributes to
      carcinogenesis but also promotes tumor metastasis. By binding to nicotinic
      acetylcholine receptors (nAChRs), nicotine induces the proliferation and
      migration of non-small cell lung cancer. Recently studies have indicated that
      alpha5-nAChR is highly associated with lung cancer risk and nicotine dependence.
      Nevertheless, it is unclear whether nicotine promotes the migration and invasion
      through activation of alpha5-nAChR in lung cancer. In the present study, A549
      cell was exposed to 1MUN nicotine for 8, 24 or 48h. Wound-healing assay and
      transwell assay were used to evaluate the capability of A549 cell migration and
      cell invasion, respectively. Silencing of alpha5-nAChR was done by siRNA. Western
      blotting and PCR were used to detect alpha5-nAChR expression. Nicotine can induce
      activation of alpha5-nAChR in association with increased migration and invasion
      of human lung cancer A549 cell. Treatment of cells with alpha5-nAChR specific
      siRNA blocks nicotine-stimulated activation of alpha5-nAChR and suppresses A549
      cell migration and invasion. Reduction of alpha5-nAChR resulted in upregulation
      of E-cadherin, consistent with E-cadherin being inhibitive of cancer cell
      invasion. These findings suggest that nicotine-induced migration and invasion may
      occur in a mechanism through activation of alpha5-nAChR, which can contribute to
      metastasis or development of human lung cancer. 

PMID- 26205097
TI  - M1-/M2-macrophages contribute to the development of GST-P-positive preneoplastic
      lesions in chemically-induced rat cirrhosis.
AB  - Glutathione S-transferase placental form (GST-P) expression in hepatocyte foci is
      regarded as a preneoplastic change in rats. We aimed to reveal the contribution
      of polarized macrophages in development of GST-P-positive pseudolobules (PLs) in
      chemically-induced rat cirrhosis. F344 rats were injected with thioacetamide
      (100mg/kg BW, twice a week, intraperitoneally). Macrophage immunophenotypes and
      expression of M1-/M2-related factors were analyzed by immunohistochemistry, real
      time RT-PCR and laser microdissection. GST-P-positive foci/clusters were clearly
      observed at post-first injection week 15. GST-P-positive PLs were distinguishable
      at weeks 20-32. Microarray analysis revealed upregulation of preneoplastic genes
      in GST-P-positive PLs at week 32. M1 (CD68(+), Iba1(+))-and M2 (CD163(+),
      CD204(+), Gal-3(+))-macrophages were greater in number in the GST-P-positive PLs,
      whereas MHC class II-positive (M1) macrophage number was fewer in the GST-P
      positive PLs. Expression of both M1 (IFN-gamma, IL-1beta, TNF-alpha, Iba1)- and
      M2 (IL-4, TGF-beta1, IL-10)-related factors were higher in GST-P-positive PLs.
      Our results showed that both M1- and M2-macrophage populations contribute to the
      development of hepatic preneoplastic lesions. MHC class II-positive macrophages
      may be related to anti-tumor progression, since their kinetics showed reverse
      pattern to other macrophage phenotypes. 

PMID- 26205098
TI  - Relationship between Cnm-positive Streptococcus mutans and cerebral microbleeds
      in humans.
AB  - OBJECTIVE: Cerebral hemorrhage has been shown to occur in animals experimentally
      infected with Streptococcus mutans carrying the collagen-binding Cnm gene.
      However, the relationship between cerebral microbleeds and oral hygiene, with a
      focus on Cnm gene-positive S. mutans infection, remains unclear. MATERIAL AND
      METHODS: One hundred and thirty-nine subjects participated. The presence or
      absence of Cnm-positive S. mutans and its collagen-binding activity were
      investigated using saliva samples, and relationship with cerebral microbleeds
      detected on MRI investigated, including clinical information and oral parameters.
      RESULTS: Fifty-one subjects were identified as Cnm-positive S. mutans carriers
      (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly
      larger number of subjects carried Cnm-positive S. mutans in the cerebral
      microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected
      in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral
      microbleeds in the Cnm-positive group was 14.4. Regarding the presence of
      cerebral microbleeds, no significant differences were noted in the number of
      remaining teeth, dental caries, or in classic arteriosclerosis risk factors.
      CONCLUSIONS: The occurrence of cerebral microbleeds was higher in subjects
      carrying Cnm-positive S. mutans, indicating that the presence of Cnm-positive S.
      mutans increases cerebral microbleeds, and is an independent risk for the
      development of cerebrovascular disorders.

PMID- 26205100
TI  - Foreword: Pediatric Rheumatology for Primary Care Clinicians--Recognizing
      Patterns of Disease.

PMID- 26205099
TI  - The self-management of longer-term depression: learning from the patient, a
      qualitative study.
AB  - BACKGROUND: Depression is a common mental health condition now viewed as chronic
      or long-term. More than 50 % of people will have at least one further episode of
      depression after their first, and therefore it requires long-term management.
      However, little is known about the effectiveness of self-management in
      depression, in particular from the patients' perspective. This study aimed to
      understand how people with longer-term depression manage the condition, how
      services can best support self-management and whether the principles and concepts
      of the recovery approach would be advantageous. METHODS: Semi-structured in depth
      interviews were carried out with 21 participants, recruited from a range of
      sources using maximum variation sampling. Interpretative Phenomenological
      Analysis was used by a diverse team comprised of service users, practitioners and
      academics. RESULTS: Four super-ordinate themes were found: experience of
      depression, the self, the wider environment, self-management strategies. Within
      these, several prominent sub-themes emerged of importance to the participants.
      These included how aspects of themselves such as hope, confidence and motivation
      could be powerful agents; and how engaging in a wide range of chosen activities
      could contribute to their emotional, mental, physical, social, spiritual and
      creative wellbeing. CONCLUSIONS: Services in general were not perceived to be
      useful in specifically facilitating self-management. Increased choice and control
      were needed and a greater emphasis on an individualised holistic model. Improved
      information was needed about how to develop strategies and locate resources,
      especially during the first episode of depression. These concepts echoed those of
      the recovery approach, which could therefore be seen as valuable in aiding the
      self-management of depression.

PMID- 26205101
TI  - Pediatric Rheumatology for the Primary Care Clinicians-Recognizing Patterns of
      Disease.
AB  - This review presents a diagnostic approach to musculoskeletal and rheumatic
      diseases in children for primary care clinicians. The focus is on juvenile
      idiopathic arthritis (JIA) as the major arthritis disease in children. It is
      necessary to know the personalities of these JIA categories. It is also crucial
      to be able to recognize the common infectious, orthopedic and mechanical,
      malignant, genetic, other rheumatic diseases, and other miscellaneous syndromes
      that can mimic JIA. To do so requires recognition of clinical patterns using a
      thorough musculoskeletal and rheumatic history and repeated complete physical
      exams with emphasis on the musculoskeletal exam. It also requires targeted and
      limited laboratory testing with careful follow-up over time. 

PMID- 26205102
TI  - Coupling between MRI-assessed regional aortic pulse wave velocity and diameters
      in patients with thoracic aortic aneurysm: a feasibility study.
AB  - AIMS: Thoracic aortic aneurysm (TAA) is potentially life-threatening and requires
      close follow-up to prevent aortic dissection. Aortic stiffness and size are
      considered to be coupled. Regional aortic stiffness in patients with TAA is
      unknown. We aimed to evaluate coupling between regional pulse wave velocity
      (PWV), a marker of vascular stiffness, and aortic diameter in TAA patients.
      METHODS: In 40 TAA patients (59 +/- 13 years, 28 male), regional aortic diameters
      and regional PWV were assessed by 1.5 T MRI. The incidence of increased diameter
      and PWV were determined for five aortic segments (S1, ascending aorta; S2, aortic
      arch; S3, thoracic descending aorta; S4, suprarenal and S5, infrarenal abdominal
      aorta). In addition, coupling between regional PWV testing and aortic dilatation
      was evaluated and specificity and sensitivity were assessed. RESULTS: Aortic
      diameter was 44 +/- 5 mm for the aortic root and 39 +/- 5 mm for the ascending
      aorta. PWV was increased in 36 (19 %) aortic segments. Aortic diameter was
      increased in 28 (14 %) segments. Specificity of regional PWV testing for the
      prediction of increased regional diameter was >= 84 % in the descending thoracic
      to abdominal aorta and >= 68 % in the ascending aorta and aortic arch.
      CONCLUSION: Normal regional PWV is related to absence of increased diameter, with
      high specificity in the descending thoracic to abdominal aorta and moderate
      results in the ascending aorta and aortic arch.

PMID- 26205103
TI  - Regulating e-cigarettes to help them realise their potential as an anti-smoking
      tool.

PMID- 26205104
TI  - Examining risk factors for hypertension in Ghana: evidence from the Study on
      Global Ageing and Adult Health.
AB  - Like most countries in sub-Saharan Africa, hypertension contributes substantially
      to morbidity and mortality in Ghana, yet nationally representative studies that
      examine the odds of becoming hypertensive among Ghanaians are conspicuously
      missing. We aimed to fill this void in the literature. The data used for analysis
      came from the first wave of the Study on Global Ageing and Adult Health (SAGE),
      collected in Ghana from January 2007 to December 2008 by the World Health
      Organization (WHO). A total of 5573 respondents were sampled for the study.
      Random-effects C-log-log models were employed in examining socio-economic,
      lifestyle and psychosocial factors on the odds of becoming hypertensive in Ghana.
      Separate models were run for male and females. Results indicated there were
      strong significant associations between socio-economic, lifestyle and
      psychosocial factors on the likelihood of becoming hypertensive, among Ghanaian
      men and women. Compared with the poorest, Ghanaians from wealthy households were
      significantly more likely to be hypertensive. Educated women, as compared with
      the uneducated, were also more likely to be hypertensive. Ghanaians who engaged
      in vigorous or intensive activities continuously, for at least 10 minutes, were
      significantly less likely to be hypertensive, compared to those who did not.
      Happier men had lower odds of becoming hypertensive, and depressed women had
      increased odds of reporting they were hypertensive.

PMID- 26205106
TI  - David Weyhe Smith, MD (1926-1981)--The Father of Dysmorphology.

PMID- 26205105
TI  - Structural prerequisites for G-protein activation by the neurotensin receptor.
AB  - We previously determined the structure of neurotensin receptor NTSR1 in an active
      like conformation with six thermostabilizing mutations bound to the peptide
      agonist neurotensin. This receptor was unable to activate G proteins, indicating
      that the mutations restricted NTSR1 to relate agonist binding to G-protein
      activation. Here we analyse the effect of three of those mutations (E166A(3.49),
      L310A(6.37), F358A(7.42)) and present two structures of NTSR1 able to catalyse
      nucleotide exchange at Galpha. The presence of F358(7.42) causes the conserved
      W321(6.48) to adopt a side chain orientation parallel to the lipid bilayer
      sealing the collapsed Na(+) ion pocket and linking the agonist with residues in
      the lower receptor part implicated in GPCR activation. In the intracellular
      receptor half, the bulkier L310(6.37) side chain dictates the position of
      R167(3.50) of the highly conserved D/ERY motif. These residues, together with the
      presence of E166(3.49) provide determinants for G-protein activation by NTSR1. 

PMID- 26205107
TI  - Immunization Update V.
AB  - With all the new vaccines and strategies for prevention, the most important
      challenge that one continues to talk about globally and at home is the one
      presented by ongoing transmission of diseases for which excellent vaccines
      already exist. As pediatricians, this presents a constant reminder to keep the
      conversation about the importance of vaccine-preventable diseases with the
      patients and their families going at every possible opportunity possible. One
      needs to constantly remind oneself that every case of a vaccine-preventable
      disease is a missed opportunity for prevention. One must also have a broader
      perspective for global eradication of vaccine-preventable disease and advocate
      for availability of vaccines globally at affordable cost and encourage local
      vaccine development.

PMID- 26205108
TI  - Salmonella Infections in Childhood.
AB  - Salmonella are gram-negative bacilli within the family Enterobacteriaceae. They
      are the cause of significant morbidity and mortality worldwide. Animals (pets)
      are an important reservoir for nontyphoidal Salmonella, whereas humans are the
      only natural host and reservoir for Salmonella Typhi. Salmonella infections are a
      major cause of gastroenteritis worldwide. They account for an estimated 2.8
      billion cases of diarrheal disease each year. The transmission of Salmonella is
      frequently associated with the consumption of contaminated water and food of
      animal origin, and it is facilitated by conditions of poor hygiene. Nontyphoidal
      Salmonella infections have a worldwide distribution, whereas most typhoidal
      Salmonella infections in the United States are acquired abroad. In the United
      States, Salmonella is a common agent for food-borne-associated infections.
      Several outbreaks have been identified and are most commonly associated with
      agricultural products. Nontyphoidal Salmonella infection is usually characterized
      by a self-limited gastroenteritis in immunocompetent hosts in industrialized
      countries, but it may also cause invasive disease in vulnerable individuals (eg,
      children less than 1 year of age, immunocompromised). Antibiotic treatment is not
      recommended for treatment of mild to moderate gastroenteritis by nontyphoidal
      Salmonella in immunocompetent adults or children more than 1 year of age.
      Antibiotic treatment is recommended for nontyphoidal Salmonella infections in
      infants less than 3 months of age, because they are at higher risk for bacteremia
      and extraintestinal complications. Typhoid (enteric) fever and its potential
      complications have a significant impact on children, especially those who live in
      developing countries. Antibiotic treatment of typhoid fever has become
      challenging because of the emergence of Salmonella Typhi strains that are
      resistant to classically used first-line agents: ampicillin, trimethoprim
      sulfamethoxazole, and chloramphenicol. The choice of antibiotics for the
      management of typhoid fever should be guided by the local resistance pattern.
      Recommendations include using an extended spectrum cephalosporin, azithromycin,
      or a fluoroquinolone. Fecal carriage of Salmonella is an important factor in the
      spread of the organism to healthy individuals. The most important measures to
      prevent the spread and outbreaks of Salmonella infections and typhoid fever are
      adequate sanitation protocols for food processing and handling as well as hand
      hygiene. In the United States, 2 vaccines are commercially available against
      Salmonella Typhi. The WHO recommends the use of these vaccines in endemic areas
      and for outbreak control.

PMID- 26205109
TI  - Childhood Tuberculosis: An Overview.

PMID- 26205110
TI  - Child Advocacy in the Twenty-first Century.

PMID- 26205111
TI  - Children in Immigrant Families: The Foundation for America's Future.

PMID- 26205113
TI  - Evidence-Based Psychological Treatments of Pediatric Mental Disorders.
AB  - With many youth presenting to primary care settings for mental health
      difficulties, knowledge of the respective evidence-based psychotherapies is
      imperative in ensuring that these youth receive the appropriate interventions in
      a timely manner. Most frequently, children present with internalizing and/or
      externalizing disorders, which cover a broad range of common pediatric mental
      disorders. Treatments of these disorders generally incorporate cognitive and/or
      behavioral components, which are derived from theoretical underpinnings and
      empirical support. Although the interventions share common components, they are
      distinctive in nature and are further tailored toward the idiosyncratic needs of
      children and their families. Careful consideration of the apposite intervention
      and individual needs of youth are pertinent to the effective amelioration of
      symptomology.

PMID- 26205112
TI  - Preparing for Transition from Pediatric to Adult Care: Evaluation of a Physician
      Training Program.

PMID- 26205114
TI  - Gene Therapy for Blinding Pediatric Eye Disorders.

PMID- 26205115
TI  - Screening for Critical Congenital Heart Disease in Newborns.
AB  - CCHD affects more than 25% of neonates born with congenital heart disease.
      Patients with CCHD require timely intervention in the form of surgery or cardiac
      catheterization to survive. These interventions may improve survival and outcomes
      for these patients. There is strong evidence that performing newborn pulse
      oximetry screening after the first 24 hours of life may help to detect more than
      1200 neonates in the United States each year with CCHD. Pulse oximetry screening
      for CCHD has been demonstrated to be reasonable to implement and seems to be cost
      effective. There is evidence that asymptomatic patients with CCHD can be
      diagnosed before clinical presentation or cardiovascular collapse with this
      screening. Pulse oximeter screening has been endorsed by several national
      organizations as a valuable newborn screening tool. Implementation of pulse
      oximetry screening programs in a standardized manner with strong communication
      among all involved parties will likely improve outcomes as well. As we move
      forward, we as clinicians should work to have a centralized system of reporting
      positive CCHD results, prompt patient evaluation, and good follow-up for the
      families of those neonates with positive screening results. Achieving these
      objectives will likely help us to achieve the goal of improving outcomes of the
      most critical neonates with CCHD.

PMID- 26205116
TI  - Vascular Anomalies in Pediatrics.
AB  - A standardized classification system allows improvements in diagnostic accuracy.
      Multidisciplinary vascular anomaly centers combine medical, surgical, radiologic,
      and pathologic expertise. This collaborative approach tailors treatment and
      management of vascular anomalies for affected individuals.

PMID- 26205117
TI  - Hypo and Hyper: Common Pediatric Endocrine and Metabolic Emergencies.
AB  - The presentation of endocrine and metabolic emergencies represents one of the
      more challenging clinical scenarios faced by pediatricians and emergency
      providers. In this review, the authors attempt to describe some of the more
      common entities that a provider may see and provide a guide for the recognition
      and management of these difficult-to-assess and often very ill children.

PMID- 26205118
TI  - Pediatric Headaches.
AB  - Pediatric headaches are common, and many may never require intervention by a
      health care provider. However, migraines can become more difficult to treat,
      especially if they become chronic daily headaches. Pediatric headache is a
      subjective and unique experience that requires attention to both psychological
      and physiologic components in diagnosis and treatment. A biopsychosocial,
      multidisciplinary approach, including both medication management and
      psychological treatment, is considered essential for effective management.

PMID- 26205119
TI  - Advances in Pediatrics. Introduction.

PMID- 26205120
TI  - Framework structured Na4Mn4Ti5O18 as an electrode for Na-ion storage hybrid
      devices.
AB  - In this study, framework structured Na4Mn4Ti5O18 possessing S-shaped tunnels for
      sodium intercalation is reported as an electrode for hybrid sodium ion batteries.
      Galvanostatic cycling of Na4Mn4Ti5O18vs. Na in the voltage region from 1.5 V to
      3.95 V exhibits a capacity of 102 mA h g(-1) at 0.1C rate corresponding to a
      specific capacitance of 149 F g(-1) with a capacity retention of 90% over 50
      cycles. The electrochemical analysis using CV measurements revealed the charge
      storage involving intercalation and pseudocapacitance. For instance, total charge
      storage of 345 C g(-1) is observed at 0.01 mV s(-1), which is attributed to 63%
      intercalation and 37% capacitance. Na4Mn4Ti5O18 was also studied for sodium ion
      storage in an aqueous medium. It delivered a capacity of 36 mA h g(-1) (144 F g(
      1)) in the voltage window of 0-0.8 V. 

PMID- 26205121
TI  - Partial trapeziectomy and interposition of fascia lata allograft in the operative
      treatment of thumb base osteoarthritis.
AB  - AIM: The purpose of this retrospective cohort study was to evaluate the results
      of fascia lata allograft interposition after partial trapeziectomy in patients
      with symptomatic first carpometacarpal joint osteoarthritis. METHODS AND RESULTS:
      Twenty-one patients (22 thumbs) with Eaton-Glickel stage II or III first
      carpometacarpal joint osteoarthritis were included. After a mean follow-up
      duration of 70.2 months, most patients experienced minimal pain. The operation
      was graded excellent or good by 15 patients (15 hands). Active range of motion
      and strength measurements were comparable to the contralateral hand, except for
      extension, which was slightly better in the contralateral hand. The mean
      radiologically measured difference pre- and postoperatively in distance between
      distal part of the trapezium and base of the metacarpal was 2.7 mm. Two patients
      had reoperations in the first year after the initial operation because of ongoing
      pain. CONCLUSION: Partial trapeziectomy with interposition of fascia lata
      allograft in patients with symptomatic first carpometacarpal joint osteoarthritis
      can achieve reasonable results. It may be considered a reliable operative
      treatment option in patients with first carpometacarpal joint osteoarthritis.

PMID- 26205122
TI  - A large-scale in vivo RNAi screen to identify genes involved in Notch-mediated
      follicle cell differentiation and cell cycle switches.
AB  - During Drosophila oogenesis, follicle cells sequentially undergo three distinct
      cell-cycle programs: the mitotic cycle, endocycle, and gene amplification. Notch
      signaling plays a central role in regulating follicle-cell differentiation and
      cell-cycle switches; its activation is essential for the mitotic cycle/endocycle
      (M/E) switch. Cut, a linker between Notch signaling and cell-cycle regulators, is
      specifically downregulated by Notch during the endocycle stage. To determine how
      signaling pathways coordinate during the M/E switch and to identify novel genes
      involved in follicle cell differentiation, we performed an in vivo RNAi screen
      through induced knockdown of gene expression and examination of Cut expression in
      follicle cells. We screened 2205 RNAi lines and found 33 genes regulating Cut
      expression during the M/E switch. These genes were confirmed with the staining of
      two other Notch signaling downstream factors, Hindsight and Broad, and validated
      with multiple independent RNAi lines. We applied gene ontology software to find
      enriched biological meaning and compared our results with other publications to
      find conserved genes across tissues. Specifically, we found earlier endocycle
      entry in anterior follicle cells than those in the posterior, identified that the
      insulin-PI3K pathway participates in the precise M/E switch, and suggested Nejire
      as a cofactor of Notch signaling during oogenesis. 

PMID- 26205124
TI  - Hypoxia-inducible miR-182 enhances HIF1alpha signaling via targeting PHD2 and
      FIH1 in prostate cancer.
AB  - Activation of hypoxia-inducible factor 1alpha (HIF1alpha) controls the
      transcription of genes governing angiogenesis under hypoxic condition during
      tumorigenesis. Here we show that hypoxia-responsive miR-182 is regulated by
      HIF1alpha at transcriptional level. Prolyl hydroxylase domain enzymes (PHD) and
      factor inhibiting HIF-1 (FIH1), negative regulators of HIF1 signaling, are direct
      targets of miR-182. Overexpression of miR-182 in prostate cancer cells led to a
      reduction of PHD2 and FIH1 expression and an increase in HIF1alpha level either
      under normoxic or hypoxic condition. Consistently, inhibition of miR-182 could
      increase PHD2 and FIH1 levels, thereby reducing the hypoxia-induced HIF1alpha
      expression. Matrigel plug assay showed that angiogenesis was increased by miR-182
      overexpression, and vice versa. miR-182 overexpression in PC-3 prostate cancer
      xenografts decreased PHD2 and FIH1 expression, elevated HIF1alpha protein levels,
      and increased tumor size. Lastly, we revealed that the levels of both miR-182 and
      HIF1alpha were elevated, while the expression PHD2 and FIH1 was downregulated in
      a mouse model of prostate cancer. Together, our results suggest that the
      interplay between miR-182 and HIF1alpha could result in a sustained activation of
      HIF1alpha pathway, which might facilitate tumor cell adaption to hypoxic stress
      during prostate tumor progression. 

PMID- 26205125
TI  - Comorbidities, intensity, frequency and duration of pain, daily functioning and
      health care seeking in local, regional, and widespread pain - a descriptive
      population-based survey (SwePain).
AB  - BACKGROUND: The clinical knowledge of factors related to the spread of pain on
      the body has increased and understanding these factors is essential for effective
      pain treatment. This population-based study examines local (LP), regional (RP),
      and widespread pain (WSP) on the body regarding comorbidities, pain aspects, and
      impact of pain and elucidates how the spread of pain varies over time. MATERIAL
      AND METHODS: A postal questionnaire that addressed pain aspects (intensity,
      frequency, duration and anatomical spreading on a body manikin), comorbidities
      and implications of pain (i.e., work situation, physical activity, consumption of
      health care and experience of hospitality and treatment of health care) was sent
      to 9000 adults living in southeastern Sweden. Of these, 4774 (53 %) completed and
      returned the questionnaire. After 9 weeks, a follow-up questionnaire was sent to
      the 2983 participants who reported pain in the first questionnaire (i.e. 62 % of
      4774 subjects). Of these, 1940 completed and returned the questionnaire (i.e. 65
      % of 2983 subjects). The follow-up questionnaire included the same items as the
      first questionnaire. RESULTS: This study found differences in intensity,
      frequency and duration of pain, comorbidities, aspects of daily functioning and
      health care seeking in three pain categories based on spreading of pain: LP, RP
      and WSP. Compared to the participants with RP and LP, the participants with WSP
      had lower education and worse overall health, including more frequent heart
      disease and hypertension. In addition, participants with WSP had more intense,
      frequent, and long-standing pain, required more medical consultations, and
      experienced more impact on work. The participants with RP constituted an
      intermediate group regarding frequency and intensity of pain, and impact on work.
      The participants with LP were the least affected group regarding these factors. A
      substantial transition to RP had occurred by the 9-week follow-up. CONCLUSIONS:
      This study shows an association between increased spread of pain and prevalence
      of heart disease, hypertension, more severe pain characteristics (i.e.,
      intensity, frequency and duration), problems with common daily activities and
      increased health care seeking. The WSP group was the most affected group and the
      LP group was the least affected group. Regarding these factors, RP was an obvious
      intermediate group. The transitions between the pain categories warrant research
      that broadly investigates factors that increase and decrease pain.

PMID- 26205126
TI  - The influence of social support on ethnic differences in well-being and
      depression in adolescents: findings from the prospective Olympic Regeneration in
      East London (ORiEL) study.
AB  - PURPOSE: This study examines the extent to which in adolescent positive mental
      well-being and depressive symptoms vary across ethnic groups, and prospectively
      examines whether social support is protective against low/poor well-being and
      depression. METHODS: A longitudinal survey of 2426 adolescents from the Olympic
      Regeneration in East London study measured well-being and depressive symptoms at
      baseline at ages 11-12 and at follow-up two years later at ages 13-14. Social
      support was assessed at ages 11-12 years by the Multidimensional Scale of
      Perceived Social Support, by the level of parental support for school, by the
      frequency of family activities and by friendship choices. Ethnic differences in
      well-being and depression in Bangladeshi (N = 337) and Black African (N = 249)
      adolescents compared to their White UK counterparts (N = 380) were estimated
      adjusted stepwise for socio-demographic factors and domains of social support.
      RESULTS: Black African and Bangladeshi adolescents scored significantly higher
      for well-being than their White UK counterparts. There were no significant ethnic
      differences in the prevalence of depressive symptoms. Lower levels of social
      support were prospectively associated with lower well-being and higher rates of
      depression in all ethnic groups. Adjustment for multiple domains of social
      support did not account for ethnic differences in well-being. CONCLUSION:
      Bangladeshi and Black African adolescents in East London may have a positive
      mental health advantage over their White UK counterparts though social support
      did not fully explain this difference. Further investigation of the reasons for
      lower well-being in the White UK group is needed.

PMID- 26205127
TI  - A weighted method for estimation of receptor occupancy for pharmacodynamic
      measurements in drug development.
AB  - BACKGROUND: Flow cytometry-based receptor occupancy (RO) assessments for
      pharmacodynamic (PD) response measurements along with drug pharmacokinetic (PK)
      measurements represent a cornerstone in mechanism based PK/PD modeling of drugs
      against cell surface targets. This report describes the utility of using a "Free"
      and a "Bound" assay in combination to derive RO estimations through a weighted
      calculation method. METHODS: Data from a RO assay validation study in human
      samples was used to explore the performance of various RO data calculation
      methods. The calculation methods were subsequently applied to investigate the
      best method to generate RO data in a first in human phase 1 clinical trial.
      Finally, the outcome of the analysis was used for PK/PD modeling of a prospective
      phase 2a trial. RESULTS: The validation data assessment demonstrated that a
      weighted RO calculation method had a better performance in terms of precision,
      accuracy and dynamic range. In the phase 1 clinical trial data analysis the
      weighted method again demonstrated a better performance resulting in a more
      robust RO estimation, and subsequently also generating a more reliable PK/PD
      simulation for the phase 2a trial. CONCLUSIONS: This report demonstrated the
      utility of using a combined "Free" and "Bound" RO assessment together with a
      weighted calculation method to better support mechanism-based PK/PD modeling
      activities.

PMID- 26205132
TI  - Recycling and incineration, contradiction or coexistence?

PMID- 26205133
TI  - Systematic review of the use of platelet-rich plasma in aesthetic dermatology.
AB  - Platelet-rich plasma (PRP) is a highly concentrated autologous solution of plasma
      prepared from a patient's own blood. PRP contains platelets that are purported to
      release numerous growth factors that may be valuable in numerous dermatologic
      applications. Here, we review systematically the clinical cosmetic applications
      of PRP including: androgenetic alopecia, scar revision, acne scars, skin
      rejuvenation, dermal augmentation, and striae distensae to understand the
      potential and best practices for PRP use. A systematic search was conducted on
      three databases: Pubmed, Embase, and Web of Science. Publications were included
      if they were in English, investigated the clinical applications of PRP in
      aesthetic dermatology and reported clinical results either as case reports or
      clinical studies. There were a total of 22 manuscripts that fulfilled these
      criteria. Four evaluated hair-related applications, eight evaluated the treatment
      of scars and postprocedure recovery, eight evaluated skin rejuvenation and dermal
      augmentation, and two evaluated treatment of striae distensae. PRP is a
      relatively new treatment modality with studies suggesting its utility in
      aesthetic dermatology. The combination of PRP with other therapies is
      particularly interesting. Future studies should include controls, including
      incorporation of split-face comparisons, to reduce intersubject variability. 

PMID- 26205134
TI  - Rapid rituximab infusion is safe in paediatric and young adult patients with non
      malignant indications.

PMID- 26205135
TI  - Phosphonate monoesters on a thiacalix[4]arene framework as potential inhibitors
      of protein tyrosine phosphatase 1B.
AB  - Monoester derivatives of thiacalix[4]arene tetrakis(methylphosphonic) acid were
      found to be capable of inhibiting protein tyrosine phosphatase 1B. In addition,
      these compounds can strongly bind to human serum albumin. 

PMID- 26205136
TI  - Total antioxidant capacity is associated with mortality of patients with severe
      traumatic brain injury.
AB  - BACKGROUND: Previously, circulating total antioxidant capacity (TAC) in traumatic
      brain injury (TBI) patients has been scarcely studied and only in studies of
      small sample size (lower than 55 TBI patients). In one study were found higher
      serum TAC in non-survivor than in survivor TBI patients; however, an association
      between circulating TAC and mortality in patients with TBI has not been
      previously reported. Thus, the objective of this study was to determine whether
      there is an association between circulating TAC, peroxidation state and mortality
      in patients with severe TBI. METHODS: This was a multicenter, observational and
      prospective study was carried out in six Spanish Intensive Care Units. We
      included patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than
      9. We excluded patients with Injury Severity Score (ISS) in non-cranial aspects
      higher than 9. We measured serum TAC on day 1 of TBI. The 30-day mortality was
      established as endpoint. RESULTS: Non-surviving TBI patients (N = 27) showed
      higher serum TAC (P < 0.001) than survivor ones (N = 73). Logistic regression
      analyses showed that serum TAC higher than 2.59 nmol/mL were associated with 30
      day mortality controlling for APACHE-II and CT classification (OR = 4.40; 95% CI
      = 1.14-16.98; P = 0.03), controlling for GCS and age (OR = 5.88; 95% CI = 1.57
      22.06; P = 0.009), and controlling for CT classification and admission abnormal
      pupils (OR = 3.89; 95% CI = 1.30-11.61; P = 0.02). There was an association
      between serum TAC and malondialdehyde (a biomarker of lipid peroxidation) levels
      (rho = 0.25; p = 0.01), APACHE-II score (rho = 0.23; p = 0.03) and GCS (rho = 
      0.21; p = 0.04). CONCLUSIONS: To our knowledge, our series is the largest
      reporting data on circulating TAC in patients with severe TBI. The most relevant
      and new findings of our study were that there is an association between
      circulating TAC and peroxidation state and mortality in patients with severe TBI.

PMID- 26205137
TI  - Super-elevated LDH and thrombocytopenia are markers of a severe subtype of vaso
      occlusive crisis in sickle cell disease.

PMID- 26205138
TI  - Malignant ameloblastoma (metastatic ameloblastoma) in the lung: 3 cases of
      misdiagnosis as primary lung tumor with a unique growth pattern.
AB  - Malignant ameloblastoma (metastatic ameloblastoma, MA) is currently defined as a
      distinct pathologic entity, MA, despite its histologically benign appearance.
      According to the new criteria, the histological and clinical features of MA are
      more homogenous. Here, we report three cases of histologically confirmed
      pulmonary MA. Two of the three patients complained of chest pain as the primary
      symptom, and the other case was detected upon the evaluation of pulmonary nodules
      found during a health examination after a local recurrence of mandible
      ameloblastoma. All three patients were female with an average age of 48 years.
      The intervals between the primary ameloblastoma and metastasis to the lung were
      14 years, 19 years and 10 years, averaging 14.3 years. Prior to metastasis to the
      lung, only one patient experienced local recurrences, at 5 and 19 years after the
      primary tumor resection, while the other two patients both remained disease-free.
      Computed tomography (CT) or X-ray evaluation demonstrated multiple bilateral lung
      nodules ranging in size from several millimeters up to 2 cm. Histologically, the
      pulmonary metastatic tumors showed a unique growth pattern: the tumor cells grew
      among the interstitial alveoli but did not appear to destructively infiltrate the
      surrounding tissue. Immunohistochemically, the MA cells expressed squamous
      differentiation markers, such as CK10/13 and p63, while the alveolar epithelial
      cells stained for TTF1 and PE10. In this paper, we discuss the clinical behavior,
      differential diagnosis and unique growth pattern of pulmonary MA.

PMID- 26205139
TI  - Combination of two pathways involved in raltegravir resistance confers
      dolutegravir resistance.
AB  - OBJECTIVES: HIV-1 integration can be efficiently inhibited by strand-transfer
      inhibitors such as raltegravir, elvitegravir or dolutegravir. Three pathways
      conferring raltegravir/elvitegravir cross-resistance (involving integrase
      residues Q148, N155 and Y143) were identified. Dolutegravir, belonging to the
      second generation of strand-transfer compounds, inhibits the Y143 and N155
      pathways, but is less efficient at inhibiting the Q148 pathway. The aim of this
      study was to characterize the combination of two pathways involved in raltegravir
      resistance described in one patient failing a dolutegravir regimen for their
      propensity to confer dolutegravir resistance. METHODS: In this study, a patient
      first failing a regimen including raltegravir was treated with dolutegravir and
      showed an increase in viruses carrying a combination of two pathways (N155 and
      Q148). Impacts of these mutations on integrase activity and resistance to strand
      transfer inhibitors were characterized using both in vitro and virological
      assays. RESULTS: Our data showed that the combination of N155H, G140S and Q148H
      mutations led to strong resistance to dolutegravir. CONCLUSIONS: Combination of
      N155H, G140S and Q148H mutations originating from two distinct resistance
      pathways to raltegravir or elvitegravir led to a high level of dolutegravir
      resistance. Due to its high genetic barrier of resistance, it would be reasonable
      to use dolutegravir in first-line therapy before emergence of raltegravir or
      elvitegravir resistance.

PMID- 26205140
TI  - Ca-channel blocker-induced gingival overgrowth that improved with non-surgical
      therapy during visiting care: a case report.
AB  - OBJECTIVES: To present a case of gingival overgrowth during visiting care.
      BACKGROUND: Ca-channel blocker-induced gingival overgrowth is a well-known
      adverse event. However, only limited information on the treatment of calcium
      channel blocker-induced gingival overgrowth during visiting care has been
      reported. CLINICAL REPORT: The patient was an 88-year-old female living in a
      nursing home since dementia. She had been taking a calcium-channel blocker and
      observed gingival overgrowth. Initial therapy was performed and changed the
      antihypertensive medication from a calcium-channel blocker to an angiotensin
      converting enzyme inhibitor. After initial therapy, the gingival overgrowth
      improved significantly. In addition, the defecation rate was improved.
      CONCLUSION: This case indicated that periodontal therapy is useful even for
      dementia patients during visiting dental care.

PMID- 26205141
TI  - Cell spreading area regulates clathrin-coated pit dynamics on micropatterned
      substrate.
AB  - Clathrin-mediated endocytosis (CME) is the most characterized pathway for the
      endocytic entry of proteins and lipids at the plasma membrane of eukaryotic
      cells. Numerous studies have probed the roles of different endocytic accessory
      proteins in regulating the dynamics of clathrin-coated pit (CCP) assembly.
      However, it is not completely clear how physical cues regulate CCP dynamics. Here
      we employ microcontact printing to control cell shape and examine CCP dynamics as
      a function of cell spreading area for three differently sized cells. Cells with a
      large spreading area had more short-lived CCPs but a higher CCP initiation rate.
      Interestingly, we found that fluorescence intensity of CCPs decreased with
      increasing cell spreading area in a manner that was dependent on the cortical
      actin network. Our results point to another facet of the regulation of CCP
      dynamics, suggesting that CME may be modulated while cells change their
      mechanical state and remodel their actin cytoskeleton during various processes. 

PMID- 26205142
TI  - Current challenges in prostate cancer: an interview with Prostate Cancer UK.
AB  - In this video Q&A, we talk to Iain Frame and Sarah Cant from Prostate Cancer UK
      about the current challenges in prostate cancer research and policy and how these
      are being addressed. 

PMID- 26205143
TI  - Mark Making: Methodologies and methods (innovative practice).
AB  - Mark Making is a recently completed AHRC-funded review exploring the role of the
      participative arts for people with dementia in the UK. Key concerns underlying
      Mark Making were both how to privilege the views and feelings of people with a
      dementia and also how best to understand the value of the arts for people with a
      dementia. These issues were tackled using a variety of qualitative methods.
      Methods included a rigorous literature review, the development of a unique web
      based map locating many participative arts projects and above all working with
      people with a dementia to ascertain their views. This brief article will
      concentrate on some of the innovative methods that the Mark Making team used,
      with particular reference to comics as a mode of engagement as used in the
      Descartes project. The article will provide an insight into some of the
      methodological challenges confronted by Mark Making as well as the inspirations
      and successes that were enjoyed. 

PMID- 26205144
TI  - Measuring social integration among residents in a dementia special care unit
      versus traditional nursing home: A pilot study.
AB  - The physical and mental health of older adults with dementia is affected by
      levels of social integration. The development of dementia special care units (D
      SCU) arose, in part, to facilitate more meaningful social interactions among
      residents implying greater social integration of D-SCU residents as compared to
      residents in a traditional nursing home (TNH). But, it is unknown whether D-SCU
      residents are receiving equal or greater benefits from living on a segregated
      unit intended to enhance their social environment and integration through both
      design and staff involvement. The purpose of this study was to pilot test a
      comprehensive objective assessment to measure social integration among nursing
      home residents with dementia and to compare levels of integration of residents
      living on a D-SCU to those living in a TNH. A total of 29 residents participated
      (15 D-SCU and 14 TNH) and data were gathered from medical charts, visitor logs,
      and through direct observations. Over 1700 interactions were recorded during 143
      h of observation. Specifically, the location, context, type, quantity, and
      quality of residents' interactions were recorded. Overall, the majority of
      resident interactions were verbal and initiated by staff. Interactions were
      social in context, and occurred in public areas, such as the common room with a
      large screen TV. Average interactions lasted less than 1 min and did not change
      the resident's affect. Residents spent between 10% and 17% of their time
      interacting with other people on average. D-SCU staff were significantly more
      likely to initiate interactions with residents than TNH staff. D-SCU residents
      also experienced more interactions in the afternoons and expressed more pleasure
      and anxiety than residents in the TNH. This study helps to lay the groundwork
      necessary to comprehensively and objectively measure social integration among
      people with dementia in order to evaluate care environments.

PMID- 26205146
TI  - Regioselective and 1,2-cis-alpha-Stereoselective Glycosylation Utilizing Glycosyl
      Acceptor-Derived Boronic Ester Catalyst.
AB  - Regioselective and 1,2-cis-alpha-stereoselective glycosylations using
      1alpha,2alpha-anhydro glycosyl donors and diol glycosyl acceptors in the presence
      of a glycosyl-acceptor-derived boronic ester catalyst. The reactions proceed
      smoothly to give the corresponding 1,2-cis-alpha-glycosides with high stereo- and
      regioselectivities in high yields without any further additives under mild
      reaction conditions. In addition, the present glycosylation method was
      successfully applied to the synthesis of an isoflavone glycoside. 

PMID- 26205145
TI  - Insights into the clinical value of cyclin-dependent kinase 5 in glioma: a
      retrospective study.
AB  - BACKGROUND: Previous studies suggested that expression of cyclin-dependent kinase
      5 (CDK5) may promote the migration and invasion of human glioma cells. In this
      study, we aimed to evaluate the clinical value of CDK5 in different grades of
      glioma in relation to Ki-67 labeling index (LI). METHODS: We firstly assessed by
      immunohistochemistry the expression of CDK5 in 152 glioma tissues and 16 normal
      brain tissues and further explored the relationship between CDK5 expression and
      other clinical features. RESULTS: The positive ratio of CDK5 in gliomas (57.2%)
      was higher than that in normal brain tissues (12.5%, P=0.001). Difference of CDK5
      expression among four World Health Organization (WHO) grades was statistically
      significant (P=0.001). The significant differences of CDK5 expression were also
      observed between WHO I glioma (34.8%) and WHO III glioma (62.5%), as well as WHO
      IV glioma (82.8%; P=0.026, P<0.001, respectively). Furthermore, Spearman's rank
      correlation confirmed that CDK5 was positively correlated with the pathological
      grade of glioma (r=0.831, P<0.001). The CDK5 expression was also positively
      correlated with Ki-67 LI (r=0.347, P<0.001). CONCLUSIONS: The current result
      suggests that CDK5 may play an essential role in the tumorigenesis and
      aggressiveness of gliomas.

PMID- 26205147
TI  - Near-infrared photons: a non-invasive probe for studying bone blood flow
      regulation in humans.
AB  - The study of bone blood flow regulation in humans has always represented a
      difficult task for the clinician and the researcher. Classical measurement
      techniques imply the presence of ionizing radiation or contrast agents, or they
      are slow or cannot be repeated too often in time. In the present review, we would
      like to give a perspective on how the optical approach might overcome some of
      these problems and give unique solutions to the study of bone blood flow
      regulation. We hope that the present contribution will encourage the scientific
      community to put a greater attention on this approach. 

PMID- 26205148
TI  - Structural elucidation of gemifloxacin mesylate degradation product.
AB  - Gemifloxacin mesylate (GFM), chemically (R,S)-7-[(4Z)-3-(aminomethyl)-4
      (methoxyimino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8
      naphthyridine-3-carboxylic acid methanesulfonate, is a synthetic broad-spectrum
      antibacterial agent. Although many papers have been published in the literature
      describing the stability of fluorquinolones, little is known about the
      degradation products of GFM. Forced degradation studies of GFM were performed
      using radiation (UV-A), acid (1 mol L(-1) HCl) and alkaline conditions (0.2 mol
      L(-1) NaOH). The main degradation product, formed under alkaline conditions, was
      isolated using semi-preparative LC and structurally elucidated by nuclear
      magnetic resonance (proton - (1) H; carbon - (13) C; correlate spectroscopy -
      COSY; heteronuclear single quantum coherence - HSQC; heteronuclear multiple-bond
      correlation - HMBC; spectroscopy - infrared, atomic emission and mass
      spectrometry techniques). The degradation product isolated was characterized as
      sodium 7-amino-1-pyrrolidinyl-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8
      naphthyridine-3-carboxylate, which was formed by loss of the 3-(aminomethyl)-4
      (methoxyimino)-1-pyrrolidinyl ring and formation of the sodium carboxylate. The
      structural characterization of the degradation product was very important to
      understand the degradation mechanism of the GFM under alkaline conditions. In
      addition, the results highlight the importance of appropriate protection against
      hydrolysis and UV radiation during the drug-development process, storage,
      handling and quality control.

PMID- 26205149
TI  - A Combinatorial Photocrosslinking Method for the Preparation of Porous Structures
      with Widely Differing Properties.
AB  - A novel method for the simultaneous preparation of a large number of porous
      polymeric structures with highly differing physical properties is developed. Low
      molecular weight methacrylate end-functionalized polymers (macromers) are
      dissolved in ethylene carbonate, cooled to below the melting temperature of the
      solvent, and subsequently photocrosslinked. The crystallized and phase-separated
      ethylene carbonate is extracted with water, upon which a porous crosslinked
      polymer network is obtained. The method is applied to combinatorial mixtures of
      methacrylate end-functionalized polymers that are relevant in the biomedical
      field: poly(trimethylene carbonate-dimethacrylate), poly(D,L-lactide
      dimethacrylate), and poly(ethylene glycol-dimethacrylate) dissolved in ethylene
      carbonate at concentrations of approximately 25 wt%. In this manner, 63 different
      porous polymeric structures with a very wide range of physical properties are
      prepared simultaneously. In the hydrated state the compressive moduli of the
      prepared structures range from 0.01 to 60 MPa, as water uptake ranges between 3
      and 1500 wt%.

PMID- 26205150
TI  - Dynamic metabolic change is indicative of inflammation-induced transformation of
      hepatic cells.
AB  - The observation that prolonged inflammation plays a causative role in cancer
      development has been well documented. However, an incremental process that leads
      from healthy to malignant phenotypes has not yet been described. Experimentally
      induced hepatocellular carcinoma is considered one of the representative
      laboratory models for studying this process. Hepatic exposure to viral infection
      or toxic reagents leads to chronic inflammation and gradual transformation into
      hepatocellular carcinoma. Here we present metabolomic profiles of hepatic cells
      at different stages during inflammation-induced cellular transformation by N
      nitrosodiethylamine. Using gas chromatography-mass spectrometry, we
      quantitatively assessed the changes in cellular metabolites during the
      transformation process in hepatitis and liver cirrhosis. Further pathway analysis
      of the differentially expressed metabolites showed that carbohydrate metabolism
      and lipid metabolism were greatly altered in hepatitis and liver cirrhosis,
      respectively. Additionally, the enhanced inflammation in cirrhosis was associated
      with a shift from carbohydrate metabolism to lipid and amino acid metabolism.
      Among the differentially expressed metabolites found in diseased mouse livers, d
      glucose and d-mannitol showed the most significant changes, highlighting them as
      potential early-diagnostic biomarkers of hepatocellular carcinoma development.
      Taken together, these investigations into the dynamic metabolic changes that
      occur during the precancerous stages of hepatocellular carcinoma add to and
      refine understanding of how chronic inflammation ultimately leads to cancer.
      Furthermore, the findings set the stage for identifying metabolites that may
      serve as early-diagnostic indicators of these unfolding events. 

PMID- 26205151
TI  - Nitric oxide maintains cell survival of Trichomonas vaginalis upon iron
      depletion.
AB  - BACKGROUND: Iron plays a pivotal role in the pathogenesis of Trichomonas
      vaginalis, the causative agent of highly prevalent human trichomoniasis. T.
      vaginalis resides in the vaginal region, where the iron concentration is
      constantly changing. Hence, T. vaginalis must adapt to variations in iron
      availability to establish and maintain an infection. The free radical signaling
      molecules reactive oxygen species (ROS) and reactive nitrogen species (RNS) have
      been proven to participate in iron deficiency in eukaryotes. However, little is
      known about the roles of these molecules in iron-deficient T. vaginalis. METHODS:
      T. vaginalis cultured in iron-rich and -deficient conditions were collected for
      all experiments in this study. Next generation RNA sequencing was conducted to
      investigate the impact of iron on transcriptome of T. vaginalis. The cell
      viabilities were monitored after the trophozoites treated with the inhibitors of
      nitric oxide (NO) synthase (L-NG-monomethyl arginine, L-NMMA) and proteasome
      (MG132). Hydrogenosomal membrane potential was measured using JC-1 staining.
      RESULTS: We demonstrated that NO rather than ROS accumulates in iron-deficient T.
      vaginalis. The level of NO was blocked by MG132 and L-NMMA, indicating that NO
      production is through a proteasome and arginine dependent pathway. We found that
      the inhibition of proteasome activity shortened the survival of iron-deficient
      cells compared with untreated iron-deficient cells. Surprisingly, the addition of
      arginine restored both NO level and the survival of proteasome-inhibited cells,
      suggesting that proteasome-derived NO is crucial for cell survival under iron
      limited conditions. Additionally, NO maintains the hydrogenosomal membrane
      potential, a determinant for cell survival, emphasizing the cytoprotective effect
      of NO on iron-deficient T. vaginalis. Collectively, we determined that NO
      produced by the proteasome prolonged the survival of iron-deficient T. vaginalis
      via maintenance of the hydrogenosomal functions. CONCLUSION: The findings in this
      study provide a novel role of NO in adaptation to iron-deficient stress in T.
      vaginalis and shed light on a potential therapeutic strategy for trichomoniasis.

PMID- 26205152
TI  - Long-term results of middle fossa plugging of superior semicircular canal
      dehiscences: clinically and instrumentally demonstrated efficiency in a
      retrospective series of 16 ears.
AB  - The objective of this study is to report the surgical outcome after middle fossa
      approach (MFA) plugging in patients suffering from a superior semi-circular canal
      dehiscence (SCD) syndrome. This is a retrospective case review. Tertiary referral
      center. Sixteen ears in 13 patients with a SCD syndrome suffering from severe and
      disabling vestibular symptoms with a bony dehiscence on CT scan >3 mm and
      decreased threshold of cervical vestibular evoked potentials (cVEMPs). We
      assessed preoperatively: clinical symptoms, hearing, cVEMPs threshold, size of
      dehiscence and videonystagmography (VNG) with caloric and 100 Hz vibratory tests.
      Postoperatively, we noted occurrences of neurosurgical complication, evolution of
      audiological and vestibular symptoms, and evaluation of cVEMP data. Tullio's
      phenomenon was observed in 13 cases (81.3 %) and subjectively reported hearing
      loss in seven (43.7 %). All patients were so disabled that they had to stop
      working. No neurosurgical complications were observed in the postoperative
      course. In three cases (16.6 %), an ipsilateral and transitory immediate
      postoperative vestibular deficit associated with a sensorineural hearing loss
      (SNHL) was noted, which totally resolved with steroids and bed rest. All patients
      were relieved of audiological and vestibular symptoms and could return to normal
      activity with a mean follow-up of 31.1 months (range 3-95). No patient had
      residual SNHL. cVEMPs were performed in 14 ears postoperatively and were
      normalized in 12 (85.7 %). Two of the three patients operated on both sides kept
      some degree of unsteadiness and oscillopsia. MFA plugging of the superior semi
      circular canal is an efficient and non-hearing deteriorating procedure. 

PMID- 26205153
TI  - Bone conduction hearing in congenital aural atresia.
AB  - Previous researches focusing on BC hearing mechanisms proved that the two routes,
      (1) EAC sound radiation and (2) inertial of ossicular chain, partially contribute
      to normal BC hearing. Therefore, the BC hearing for those patients with
      congenital aural atresia should partially decrease theoretically due to their
      abnormal anatomy. However, there are not many studies which mention these
      patients' BC hearing up till now. The objective of this study is to investigate
      congenital aural atresia patient's BC hearing by analysis of pre-surgical
      audiogram and to study their potential BC hearing mechanisms using animal
      modeling and their ABR measurements. The study methoed involves analyzing 75
      patients' pre-operative audiogram. Then we produced an animal model by surgery to
      measure their BC hearing threshold changes. Clinical data showed that those
      patients had some BC hearing loss; and there were 25 cases (25/75, 33.3 %) which
      present with typical Carhart's Notch. The animal experiments proved that inertia
      of ossicular chain contribute to partial BC hearing, which demonstrated that the
      inertia produced more affects on high frequencies by comparing with low
      frequencies. The patients with congenital aural atresia present BC hearing loss,
      which could be mainly ascribed to the absence of inertia of ossicular chain. 

PMID- 26205154
TI  - Obesity and Antiplatelets-Does One Size Fit All?
AB  - Antiplatelet therapy has become a cornerstone in the management of many vascular
      diseases. With growing antiplatelet options, attention has focused on their
      comparative effectiveness in specific patient populations. Perhaps one of the
      least defined factors influencing efficacy of these agents is body mass and
      obesity. Evidence from preclinical models established that obesity promotes
      inflammation that in turn enhances platelet reactivity. Thus, adiposity has the
      potential to diminish or alter the therapeutic effect of antiplatelet therapy.
      Pharmacodynamic analyses suggest a potential need for dose adjustments of
      antiplatelet therapy in obese patients. Yet, obese patients paradoxically have
      better outcomes after acute coronary syndromes. In this review, we identify a
      critical need for clinical studies with outcome data to enable the development of
      recommendations for optimal antiplatelet regimens in obese individuals. Until
      such data exists, healthcare providers should be aware of the potential impact of
      obesity on the efficacy of anti-platelet therapy. 

PMID- 26205155
TI  - Regulation of tissue factor in NT2 germ cell tumor cells by cisplatin
      chemotherapy.
AB  - BACKGROUND: Patients with germ cell tumors (GCTs) receiving cisplatin-based
      chemotherapy are at increased risk of thrombosis, but the underlying cellular and
      molecular mechanisms remain obscure. OBJECTIVE: To study baseline tissue factor
      (TF) expression by GCT cell lines and its modulation by cisplatin treatment.
      METHODS: TF expression was assessed by single-stage clotting and thrombin
      generation assay, flow cytometry, ELISA, and Western blot analysis. Cell cycle
      analysis and detection of phosphatidylserine (PS) membrane exposure were carried
      out by flow cytometry. TF mRNA was analyzed by quantitative RT-PCR. RESULTS:
      Significant expression of TF-specific procoagulant activity (PCA) was detected on
      three non-seminoma (NT2, 2102Ep, NCCIT) and one seminoma cell line (TCam-2).
      Treatment with 0.4MUM cisplatin (corresponding to the IC50) for 48hrs increased
      TF PCA on NT2 cells 3-fold, an effect that was largely independent of PS exposure
      and that could not be explained by translocation of active TF from intracellular
      storage pools. Cisplatin-induced TF PCA expression in NT2 cells did not occur
      before 12hrs, but was steady thereafter and accompanied by a 2-fold increase in
      total and surface-located TF antigen. Importantly, increased TF gene
      transcription or production and release of an intermediate factor were not
      involved in this process. Cell cycle analysis suggested that cisplatin-induced
      G2/M arrest resulted in an accumulation of procoagulant TF on the membrane
      surface of NT2 cells. CONCLUSIONS: In addition to induction of apoptosis/necrosis
      with PS-mediated activation of preformed TF, cisplatin may alter the procoagulant
      phenotype of GCT cells through an increase in total cellular TF antigen.

PMID- 26205156
TI  - Patient satisfaction with family practice in Turkey: Three-year trend from 2010
      to 2012.
AB  - BACKGROUND: After the health reform in 2003, a need emerged to monitor patient
      satisfaction in Turkey. OBJECTIVE: To evaluate patient satisfaction with family
      practice in Turkey and compare with some other European countries. METHODS: The
      study was performed on a countrywide representative sample from all the 81
      provinces of Turkey. Data were collected during the years 2010-2012 from patients
      visiting family practice centres. A three-year repeated cross-sectional study was
      conducted using the EUROPEP instrument. Twenty-six questions with a five-point
      Likert scale were applied. Primary outcome measures of the study were the mean
      EUROPEP scores (min. 1, max. 5). RESULTS: Mean (+/- SD) EUROPEP scores for the
      years 2010 (n = 34 472), 2011 (n = 34 764), and 2012 (n = 32 667) were 4.09 +/-
      0.77, 4.29 +/- 0.59, and 4.42 +/- 0.54 respectively (F = 1565.37; P < 0.001). The
      mean satisfaction percentage was calculated as 88.3%. Areas of lowest
      satisfaction were 'Being able to speak to the GP on the telephone,' 'Getting
      through to the practice on the phone,' and 'Physical conditions of the family
      practice.' CONCLUSION: Although in small increments, patient satisfaction with
      family practices in Turkey has increased during the last few years.

PMID- 26205157
TI  - Impact of the sustained control of cardiovascular risk factors on first episode
      heart failure: The relevant role of primary care.
AB  - BACKGROUND: The role of cardiovascular risk factor control in the development of
      heart failure (HF) has not yet been clearly established. OBJECTIVE: To determine
      the effect of cardiovascular risk factor control on the occurrence of a first
      episode of hospital admission for HF. METHODS: A case-control study using
      propensity score-matching was carried out to analyse the occurrence of first
      hospital admission for HF taking into account the degree of cardiovascular risk
      factor control over the previous 24 months. All patients admitted to the
      cardiology unit of the Hospital del Mar between 2008 and 2011 because of a first
      episode of HF were considered cases. Controls were selected from the population
      in the hospital catchment area who were using primary care services.
      Cardiovascular risk factor measurements in the primary healthcare electronic
      medical records prior to the first HF episode were analysed. RESULTS: After the
      matching process, 645 participants were analysed (129 HF cases and 516 controls).
      Patients suffering a first HF episode had modest increments in body mass index
      and blood pressure levels during the previous two years. Adjusted odds ratio for
      experiencing a first HF hospital admission episode according to systolic blood
      pressure levels and body mass index was (OR: 1.031, 95% CI: 1.001-1.04), and (OR:
      1.09, 95% CI: 1.03-1.15), respectively. CONCLUSION: Increased levels of body mass
      index and systolic blood pressure during the previous 24 months may determine a
      higher risk of having a first HF hospital admission episode.

PMID- 26205158
TI  - Advanced Development Strategies for Biopharmaceutical Cell Culture Processes.
AB  - The shift from empirical to science-based process development is considered to be
      a key factor to increase bioprocess performance and to reduce time to market for
      biopharmaceutical products in the near future. In the last decade, expanding
      knowledge in systems biology and bioprocess technology has delivered the
      foundation of the scientific understanding of relationships between process input
      parameters and process output features. Based on this knowledge, advanced process
      development approaches can be applied to maximize process performance and to
      generate process understanding. This review focuses on tools which enable the
      integration of physiological knowledge into cell culture process development. As
      a structured approach, the availability and the proposed benefit of the
      application of these tools are discussed for the subsequent stages of process
      development. The ultimate aim is to deliver a comprehensive overview of the
      current role of physiological understanding during cell culture process
      development from clone selection to the scale-up of advanced control strategies
      for ensuring process robustness. 

PMID- 26205159
TI  - A Model for the Origin of the First mRNAs.
AB  - I present a model for the evolution of the genetic code that seems to predict, in
      a totally natural way, the origin of the first mRNAs. In particular, the model-
      bestowing to peptidated-RNAs the major catalytic role in the phase that triggered
      the genetic code origin--suggests that interactions between peptidated-RNAs led
      to the synthesis of these ancestral catalysts. Within every group of these
      interactions, a pre-mRNA molecule evolved that was able to direct all
      interactions between peptidated-RNAs of that particular group. This represented
      an improvement in the coding of these interactions compared to the interaction
      groups that did not evolve these pre-mRNAs. This would represent a natural and
      intrinsic tendency. Therefore, these molecules of pre-mRNAs were positively
      selected because they improved the synthesis of the catalysts through this first
      form of coding of interactions among peptidated-RNAs. Thus, according to the
      model were the pairings--involving a base number greater than three (ennuplet
      code)-between peptidated-RNAs and pre-mRNAs that would represent the first form
      of the genetic code. The evolution of this ennuplet code to the triplet code
      might have been simply triggered by the natural tendency to make the reading
      module-that is the interactions between peptidated-RNAs and pre-mRNAs--of the
      different ennuplets to the triplet uniform, because in this way the heterogeneity
      existing in interactions between the aminoacylated or peptidated-RNAs and pre
      mRNAs was eliminated. That is to say, there might have been the natural tendency
      toward the triplets because these would have made these interactions more
      efficient, given that the ennuplets were at least more cumbersome and therefore
      less economic and with an inferior adaptive value; and also because the triplets
      would represent the simpler choice among that available given that the doublets
      would have codified too few meanings and quartets instead too many. Therefore,
      the genetic code would result from a very long era of interactions among
      peptidated-RNAs under the continuous and fundamental selective pressure for
      improving catalysts' syntheses and thus catalysis. The model is strongly
      corroborated by the explanation that the tmRNA molecule (transfer-messenger RNA)
      would seem to be the very molecule of pre-mRNAs that the model predicts. In other
      words, the tmRNA would be the molecular fossil of the evolutionary stages that
      led to the appearance of the first mRNAs.

PMID- 26205160
TI  - An Extrusion Spheronization Approach to Enable a High Drug Load Formulation of a
      Poorly Soluble Drug with a Low Melting Surfactant.
AB  - Vitamin E tocopherol polyethylene glycol succinate (TPGS) is a non-ionic surface
      active agent, known to enhance the bioavailability of lipophilic compounds via
      wettability, solubility, and in some cases permeability enhancement. MK-0536 is
      an anti-retroviral drug with poor wettability and solubility and a high dose.
      Based on pharmacokinetic studies in dogs and humans, use of vitamin E TPGS in
      oral solid formulations of MK-0536 provides desired PK characteristics. The use
      of vitamin E TPGS, however, in solid dosage forms is limited because of the
      processing challenges resulting from its waxy nature and low melting temperature
      (~37 degrees C). The current study, for the first time, demonstrates the use of
      an alternative low pressure extrusion and spheronization approach to enable high
      loadings of the poorly soluble, poorly compactable drug and relatively high
      levels of vitamin E TPGS. This approach not only aided in mitigating processing
      challenges arising from most high energy process steps such as milling,
      compression, and coating, but also enabled a higher drug load formulation that
      provided superior bioperformance relative to a conventional high shear wet
      granulated formulation. An encapsulated dosage form consisting of pellets
      prepared by extrusion spheronization with 75% (w/w) MK-0536 and 10% (w/w) vitamin
      E TPGS was developed.

PMID- 26205161
TI  - Warring arthropod societies: Social spider colonies can delay annihilation by
      predatory ants via reduced apparency and increased group size.
AB  - Sociality provides individuals with benefits via collective foraging and anti
      predator defense. One of the costs of living in large groups, however, is
      increased apparency to natural enemies. Here, we test how the individual-level
      and collective traits of spider societies can increase the risk of discovery and
      death by predatory ants. We transplanted colonies of the social spider
      Stegodyphus dumicola into a habitat dense with one of their top predators, the
      pugnacious ant Anoplolepis custodiens. With three different experiments, we test
      how colony-wide survivorship in a predator-dense habitat can be altered by colony
      apparency (i.e., the presence of a capture web), group size, and group
      composition (i.e., the proportion of bold and shy personality types present). We
      also test how spiders' social context (i.e., living solitarily vs. among
      conspecifics) modifies their behaviour toward ants in their capture web. Colonies
      with capture webs intact were discovered by predatory ants on average 25% faster
      than colonies with the capture web removed, and all discovered colonies
      eventually collapsed and succumbed to predation. However, the lag time from
      discovery by ants to colony collapse was greater for colonies containing more
      individuals. The composition of individual personality types in the group had no
      influence on survivorship. Spiders in a social group were more likely to approach
      ants caught in their web than were isolated spiders. Isolated spiders were more
      likely to attack a safe prey item (a moth) than they were to attack ants and were
      more likely to retreat from ants after contact than they were after contact with
      moths. Together, our data suggest that the physical structures produced by large
      animal societies can increase their apparency to natural enemies, though larger
      groups can facilitate a longer lag time between discovery and demise. Lastly, the
      interaction between spiders and predatory ants seems to depend on the social
      context in which spiders reside. 

PMID- 26205162
TI  - Response to a Letter to the Editor from Katherine Rich.

PMID- 26205163
TI  - Increased Levels of Antinutritional and/or Defense Proteins Reduced the Protein
      Quality of a Disease-Resistant Soybean Cultivar.
AB  - The biochemical and nutritional attributes of two soybean (Glycine max (L.)
      Merr.) cultivars, one susceptible (Serido) and the other resistant (Serido-RCH)
      to stem canker, were examined to assess whether the resistance to pathogens was
      related to levels of antinutritional and/or defense proteins in the plant and
      subsequently affected the nutritional quality. Lectin, urease, trypsin inhibitor,
      peroxidase and chitinase activities were higher in the resistant cultivar.
      Growing rats were fed with isocaloric and isoproteic diets prepared with defatted
      raw soybean meals. Those on the Serido-RCH diet showed the worst performance in
      terms of protein quality indicators. Based on regression analysis, lectin,
      trypsin inhibitor, peroxidase and chitinase appear to be involved in the
      resistance trait but also in the poorer nutritional quality of Serido-RCH. Thus,
      the development of cultivars for disease resistance may lead to higher
      concentrations of antinutritional compounds, affecting the quality of soybean
      seeds. Further research that includes the assessment of more cultivars/genotypes
      is needed. 

PMID- 26205164
TI  - Emergency department crowding and the performance of damage control resuscitation
      in major trauma patients with hemorrhagic shock.
AB  - OBJECTIVES: Uncontrolled hemorrhagic shock is the leading cause of potentially
      preventable death in major trauma patients. Damage control resuscitation (DCR), a
      strategy combining the techniques of permissive hypotension, hemostatic
      resuscitation, and damage control surgery, has been highly recommended for trauma
      patients. This study investigated whether emergency department (ED) crowding was
      associated with poor performance of the DCR strategies in treating hemorrhagic
      shock trauma patients. METHODS: This was a retrospective cohort study in an urban
      tertiary hospital conducted from January 2010 to December 2013. Major trauma
      patients who presented to the ED with hemorrhagic shock were included. ED
      crowding, measured by ED occupancy rate, was categorized into three groups (low,
      medium, and high). The performance of DCR and inpatient outcomes were analyzed
      using multivariate logistic analysis. RESULTS: Of the 3,037 major trauma patients
      assessed, 852 met the inclusion criteria and were enrolled in the study. Patients
      in the high-crowding group had delayed initiation of transfusion (high vs. medium
      and low, 2.5 hours vs. 2.1 hours and 1.0 hours, respectively, p = 0.01), received
      less blood products in the ED (both comparisons p < 0.01), and experienced delays
      in procedures (4.5 hours vs. 3.3 hours and 2.4 hours, p < 0.01). However, the
      amount of crystalloid solution was similar among patients in all three groups (p
      = 0.17). In multivariate analysis, more patients from the high-crowding group
      developed traumatic coagulopathy in the intensive care unit (29.7% vs. 24.1% and
      16.3%, p < 0.01), while no clear relationship was found between ED crowding and
      30-day mortality or early lactate clearance rate (p > 0.05). CONCLUSIONS: ED
      crowding was associated with poor performance of DCR for major trauma patients in
      the ED. New strategies should be implemented to ameliorate crowded conditions and
      potential adverse outcomes.

PMID- 26205165
TI  - Defining failure and its predictors in mandibular distraction for Robin sequence.
AB  - INTRODUCTION: Robin sequence (RS) is defined as the triad of micrognathia,
      glossoptosis and airway obstruction. A popular surgical treatment is mandibular
      distraction osteogenesis (MDO). In this study, it is demonstrated that the
      associated variables change, dependent on the manner in which failure is defined.
      These multiple failure outcomes are used to construct a scoring system to predict
      MDO failure. METHODS: A retrospective database of neonatal MDO patients was
      constructed. Failure outcomes studied included tracheostomy; a decrease in the
      apnea-hypopnea index (AHI) but an AHI >20; and death. A combination of bivariate
      and regression analysis was used to produce significantly associated variables
      and a scoring system. RESULTS: Statistical analysis demonstrated the association
      of gastroesophageal reflux; age >30 days; neurologic anomaly; airway anomalies,
      other than laryngomalacia; an intact palate; and pre-operative intubation on the
      outcome variables studied. Multiple scoring systems were produced with reasonable
      sensitivity, specificity, and positive and negative predictive value.
      CONCLUSIONS: When reporting surgical outcomes of MDO in the setting of RS, it is
      important to consider the AHI as well as avoidance of tracheostomy as an outcome
      variable. Incomplete amelioration of AHI accounts for half of the patients with a
      problem after MDO. The predictive scores presented will be used and validated on
      a larger, prospectively collected dataset.

PMID- 26205166
TI  - The Role of the Qur'an and Sunnah in Oral Health.
AB  - The aim of this study was to explore the ways in which the main texts in Islam,
      Holy Qur'an and the Sunnah of the Prophet Mohammed (pbuh), contribute to
      understandings of oral health. The AHadith provide guidance for oral health
      related behaviour but were written at a time when their symbolic meanings were
      perhaps vastly different to those of today. In gaining more insight into the ways
      Islamic HRB shape oral health-related practices and outcomes, if at all, we may
      be better placed to develop a more culturally sensitive and diverse dental public
      health and oral health promotion which takes into account religious dimensions,
      mediating factors, HRB and salutogenic mechanisms. 

PMID- 26205168
TI  - Stress and cancer: Nordic pieces to the complex puzzle.

PMID- 26205167
TI  - Breast cancer risk and night shift work in a case-control study in a Spanish
      population.
AB  - Epidemiologic and animal data indicate that night shift work might increase the
      risk for breast cancer. We evaluated the association of night work with different
      clinical types of breast cancer in a population based case-control study (MCC
      Spain study) taking into account chronotype, an individual characteristic that
      may relate to night shift work adaptation. Lifetime occupational history was
      assessed by face-to-face interviews and shift work information was available for
      1708 breast cancer cases and 1778 population controls from 10 Spanish regions,
      enrolled from 2008 to 2013. We evaluated three shift work domains, including
      shift work type (permanent vs rotating), lifetime cumulative duration and
      frequency. We estimated odds ratios (OR) for night work compared to day work
      using unconditional logistic regression models adjusting for confounders. Having
      ever worked permanent or rotating night shift was associated with an increased
      risk for breast cancer compared to day workers [odds ratio (OR) 1.18; 95 % CI
      0.97, 1.43]. Chronotype was differentially associated with breast cancer
      depending on the duration of night shift work. Risk was higher in women with
      invasive tumors (OR 1.23; 95 % CI 1.00, 1.51) and for estrogen and progestagen
      positive tumors among premenopausal women (OR 1.44; 95 % CI 1.05, 1.99). Having
      ever performed night shift was associated with a small increased risk for breast
      cancer and especially in subgroups of women with particular hormone related
      characteristics.

PMID- 26205169
TI  - Flavonoid transport mechanisms: how to go, and with whom.
AB  - Subcellular flavonoid transport and its underlying regulatory mechanisms are
      still poorly understood, but are fascinating research frontiers in plant science.
      Recent studies support and further extend previous hypotheses indicating that
      vacuolar sequestration of flavonoids involves vesicle trafficking, membrane
      transporters, and glutathione S-transferase (GST). However, the question remains
      to be addressed of how three distinct but nonexclusive mechanisms are
      functionally integrated into diverse but redundant transport routes for vacuolar
      sequestration or extracellular secretion of flavonoids. In this review, I
      highlight recent progress in understanding flavonoid-transporting vesicle
      behavior and properties, GST and membrane transporter functions and mechanisms,
      and flavonoid transport substrate specificity and preference. 

PMID- 26205170
TI  - Genome skimming for next-generation biodiversity analysis.

PMID- 26205171
TI  - Tuning plant signaling and growth to survive salt.
AB  - Salinity is one of the major abiotic factors threatening food security worldwide.
      Recently, our understanding of early processes underlying salinity tolerance has
      expanded. In this review, early signaling events, such as phospholipid signaling,
      calcium ion (Ca(2+)) responses, and reactive oxygen species (ROS) production,
      together with salt stress-induced abscisic acid (ABA) accumulation, are brought
      into the context of long-term salt stress-specific responses and alteration of
      plant growth. Salt-induced quiescent and recovery growth phases rely on
      modification of cell cycle activity, cell expansion, and cell wall extensibility.
      The period of initial growth arrest varies among different organs, leading to
      altered plant morphology. Studying stress-induced changes in growth dynamics can
      be used for screening to discover novel genes contributing to salt stress
      tolerance in model species and crops. 

PMID- 26205173
TI  - Purpureocillium lilacinum, potential agent for biological control of the leaf
      cutting ant Acromyrmex lundii.
AB  - Many leaf-cutter ant species are well known pests in Latin America, including
      species of the genera Acromyrmex and Atta. An environmentally friendly strategy
      to reduce the number of leafcutter ants and avoid indiscriminate use of chemical
      pesticides is biological control. In this work we evaluated the effectiveness of
      a strain of the entomopathogen Purpureocillium lilacinum, against worker ants
      from six Acromyrmex lundii field colonies, after immersions in pure suspensions
      at a concentration of 1*10(6)conidiaml(-1). Survival of ants treated with P.
      lilacinum was significantly lower than that recorded in controls, and median
      lethal time (LT50) was 6-7days. P. lilacinum was responsible for 85.6% (80.6
      89.7) of the mortality in inoculated ants, in which we found that the percentage
      of other entomopathogens that naturally infected ants decreased also, suggesting
      a good competitive capability of the fungus. Horizontal transmission to non
      inoculated ants was also evidenced, given that 58.5% (41.9-64.2) of them died
      because of P. lilacinum. Moreover, we tested pathogenicity for three
      concentrations of this strain (1.0*10(4), 10(6) and 10(8)conidiaml(-1)) and found
      a significantly faster mortality of ants and greater median percentage of
      infection at 10(8)conidiaml(-1) of P. lilacinum. CL50 value was
      2.8*10(5)conidiaml(-1). We thus propose the use of P. lilacinum as a biological
      control agent of leafcutter ants in crops and plantations. 

PMID- 26205172
TI  - Evaluation of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry (MALDI-TOF MS) for identification and clustering of Neisseria
      gonorrhoeae.
AB  - BACKGROUND: The sexually transmitted infection gonorrhea remains a public health
      concern for becoming resistant to drug treatments available. The purpose of this
      study was to evaluate the usefulness of the matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS) to identify and
      cluster Neisseria gonorrhoeae. From a current monitoring in Italy, as part of the
      European Gonococcal Antimicrobial Surveillance Programme (EURO-GASP), 93
      gonococci collected from 2007 to 2012 susceptible (44 isolates) and resistant (49
      isolates) to cefixime were selected. Minimum Inhibitory Concentration (MIC)
      values for cefixime was assessed by Etest carried out in agreement with the
      manufacturer's instructions and interpreted referring to European Committee on
      Antimicrobial Susceptibility testing (EUCAST) clinical breakpoints criteria. Data
      obtained by N. gonorrhoeae multiantigen sequence typing (NG-MAST) and the
      dendrogram based on the concatenation of porB and tbpB genes were evaluated.
      MALDI-TOF MS, to reconfirm gonorrhea identification, analyzed single colonies
      from freshly grown isolates and applied directly on a ground-steel MALDI target
      plate. For the MALDI-TOF dendrogram cluster analysis, MSPs (Main Spectrum
      Profile) from each isolate were created acquiring 5000 shots from 10 technical
      replicates obtained from bacteria extraction. RESULTS: Molecular typing by NG
      MAST showed 28 sequence types (STs); G1407 was the predominant accounting for 75
      gonococci. All the 93 gonococci, except one, were correctly identified at species
      level by MALDI-TOF MS and G1407 isolates were divided into two clusters.
      CONCLUSION: MALDI-TOF MS for a real-time detection and cluster analysis of
      gonorrhea is a promising tool for surveillance purposes. Moreover, additional
      studies are required to collect more data on the performance of MALDI-TOF MS for
      gonococci.

PMID- 26205174
TI  - Identification, inheritance, and fitness costs of Cry2Ab2 resistance in a field
      derived population of sugarcane borer, Diatraea saccharalis (F.) (Lepidoptera:
      Crambidae).
AB  - The sugarcane borer, Diatraea saccharalis (F.), is one of the major target pests
      of transgenic maize, Zea mays, expressing Bacillus thuringiensis (Bt) proteins in
      South America and mid-southern region of the U.S. The MON89034 maize expresses
      Cry2Ab2 and Cry1A.105 Bt proteins and it was developed to provide better control
      of key lepidopteran pests of maize including D. saccharalis. The objectives of
      this study were to select and characterize the resistance of D. saccharalis to
      Cry2Ab2 using a non-commercial Cry2Ab2 single gene Bt maize line. A Cry2Ab2
      resistant strain (Cry2Ab2-RR) of D. saccharalis was established from 28 two
      parent families collected from fields in northeast Louisiana, U.S. The Cry2Ab2-RR
      showed a high level of resistance to Cry2Ab2 in both diet-incorporated and whole
      maize plant bioassays. The Cry2Ab2 resistance in D. saccharalis was likely
      inherited as a single or a few tightly linked autosomal genes. The resistance was
      non-recessive and not associated with fitness costs. The results should provide
      valuable information in resistance monitoring, assessing resistance risk, and
      developing effective management strategies for the sustainable use of Bt maize
      technology for managing maize stalk borers. 

PMID- 26205175
TI  - Commonalities and specificities between attention deficit/hyperactivity disorder
      and autism-spectrum disorders: can epidemiology contribute?

PMID- 26205177
TI  - Leaf movements and their relationship with the lunisolar gravitational force.
AB  - BACKGROUND: Observation of the diurnal ascent and descent of leaves of beans and
      other species, as well as experimental interventions into these movements, such
      as exposures to light at different times during the movement cycle, led to the
      concept of an endogenous 'clock' as a regulator of these oscillations. The
      physiological basis of leaf movement can be traced to processes that modulate
      cell volume in target tissues of the pulvinus and petiole. However, these
      elements of the leaf-movement process do not completely account for the rhythms
      that are generated following germination in constant light or dark conditions, or
      when plants are transferred to similar free-running conditions. SCOPE: To develop
      a new perspective on the regulation of leaf-movement rhythms, many of the
      published time courses of leaf movements that provided evidence for the concept
      of the endogenous clock were analysed in conjunction with the contemporaneous
      time courses of the lunisolar tidal acceleration at the relevant experimental
      locations. This was made possible by application of the Etide program, which
      estimates, with high temporal resolution, local gravitational changes as a
      consequence of the diurnal variations of the lunisolar gravitational force due to
      the orbits and relative positions of Earth, Moon and Sun. In all cases, it was
      evident that a synchronism exists between the times of the turning points of both
      the lunisolar tide and of the leaftide when the direction of leaf movement
      changes. This finding of synchrony leads to the hypothesis that the lunisolar
      tide is a regulator of the leaftide, and that the rhythm of leaf movement is not
      necessarily of endogenous origin but is an expression of an exogenous lunisolar
      'clock' impressed upon the leaf-movement apparatus. CONCLUSIONS: Correlation
      between leaftide and Etide time courses holds for leaf movement rhythms in
      natural conditions of the greenhouse, in conditions of constant light or dark,
      under microgravity conditions of the International Space Station, and also holds
      for rhythms that are atypical, such as pendulum and relaxation rhythms whose
      periods are longer or shorter than usual. Even the apparently spontaneous short
      period, small-amplitude rhythms recorded from leaves under unusual growth
      conditions are consistent with the hypothesis of a lunisolar zeitgeber. Two
      hypotheses that could account for the synchronism between leaftide and Etide, and
      which are based on either quantum considerations or on classical Newtonian
      physics, are presented and discussed.

PMID- 26205176
TI  - Depressive symptom severity is associated with increased cortical thickness in
      older adults.
AB  - OBJECTIVE: Structural neuroimaging studies in older adults have consistently
      shown volume reductions in both major and subthreshold depression. Cortical
      thickness, another measure of brain structure, has not been well studied in this
      population. We examined cortical thickness in older adults across a range of
      depressive symptom (DS) severity. METHODS: Forty-three community-dwelling older
      adults (mean age = 68.80 +/- 7.00 years) underwent magnetic resonance imaging.
      Based on a priori hypotheses, we examined cortical thickness in regions of
      interest in the rostral anterior cingulate, orbitofrontal cortex, middle frontal
      gyrus, and isthmus cingulate using multiple linear regressions with depression
      questionnaire scores as the independent variable and age, sex, and mean
      hemispheric thickness as covariates. We also performed an exploratory vertex-wise
      analysis. RESULTS: After correction for multiple comparisons, we found an
      association between increased DSs and greater cortical thickness in the right
      isthmus cingulate (F(1, 38) = 8.09, false discovery rate corrected p = 0.028;
      R(2) = 35.78) in the region of interest analysis and in the left precuneus
      (cluster size = 413, p = 0.00002) in the vertex-wise analysis. CONCLUSIONS: Older
      adults with higher DSs also have greater cortical thickness in the isthmus
      cingulate and precuneus, areas important for emotion regulation and self
      referential processing. Additional research is needed to elucidate the mechanisms
      and potential clinical significance underlying this relationship.

PMID- 26205179
TI  - Asymmetry in the discrimination of quantity by rats: The role of the intertrial
      interval.
AB  - In three experiments, rats were trained to discriminate between 20 and five
      (Exps. 1 and 2), or between 40 and five (Exp. 3), black squares. The squares were
      randomly distributed in the center of a white background and displayed on a
      computer screen. For one group, the patterns containing the higher quantity of
      squares signaled the delivery of sucrose (+), whilst patterns with the lower
      quantity of squares did not (-). For the second group, sucrose was signaled by
      the lower, but not by the higher, quantity of squares. In Experiment 1, the
      intertrial interval (ITI) was a white screen, and the 20+/5- discrimination was
      acquired more readily than the 5+/20- discrimination. For Experiment 2, the ITI
      was made up of 80 black squares on a white background. In this instance, the
      5+/20- discrimination was acquired more successfully than the 20+/5-
      discrimination. In Experiment 3, two groups were trained with a 40+/5-
      discrimination, and two with a 5+/40- discrimination. For one group from each of
      these pairs, the training trials were separated by a white ITI, and the 40+/5-
      discrimination was acquired more readily than the 5+/40- discrimination. For the
      remaining two groups, the training trials were not separated by an ITI, and the
      two groups acquired the task at approximately the same rate. The results indicate
      that the cues present during the ITI play a role in the asymmetrical acquisition
      of magnitude discriminations based on quantity. 

PMID- 26205181
TI  - Pigmented hepatocellular adenomas have a high risk of atypia and malignancy.
AB  - Pigment deposition is occasionally seen in hepatocellular adenomas. Several
      reports suggest that pigmented hepatocellular adenomas have increased risk of
      malignancy, but these tumors remain incompletely understood. To determine the
      frequency of pigment deposition, we evaluated and classified 109 well
      differentiated hepatocellular neoplasms that were originally diagnosed or
      submitted in consultation as hepatocellular adenomas and found 27 (25%) pigmented
      tumors. All were negative on iron stain and in three cases electron microscopy
      confirmed the pigment was lipofuscin. The lipofuscin intensely stained with
      glypican-3 in most cases (89%). Of the 27 pigmented tumors, 11 cases (41%) were
      classified as hepatocellular adenomas, 7 cases (27%) were classified as atypical
      hepatocellular adenomas/hepatocellular neoplasms of uncertain malignant
      potential, and 9 cases (33%) were reclassified as well-differentiated
      hepatocellular carcinomas. Four (of 9) hepatocellular carcinomas arose in
      pigmented hepatocellular adenomas, giving a rate of malignant transformation in
      pigmented hepatocellular adenomas of 27%. Of the total 27 pigmented tumors, 78%
      were in women and 22% in men, but interestingly only men had tumors classified as
      hepatocellular carcinoma or hepatocellular neoplasm of uncertain malignant
      potential. Also of note, a total of 10 individuals (37%) had multiple
      hepatocellular neoplasms but in 9 of these cases the other adenomas were non
      pigmented. Importantly, in cases with multiple hepatocellular neoplasms, only the
      pigmented hepatocellular neoplasms had atypia or malignancy. Genotype-phenotype
      classification of the pigmented tumors showed different subtypes: HNF1alpha
      inactivated (48%), beta-catenin activated (26%), inflammatory (15%), concurrently
      beta-catenin activated and inflammatory in 1 hepatocellular adenoma, concurrently
      HNF-1alpha inactivated and beta-catenin activated in 1 hepatocellular adenoma,
      and unclassified in 1 hepatocellular carcinoma. In conclusion, hepatocellular
      adenomas with lipofuscin pigment are a heterogeneous group of adenomas, with HNF
      1alpha inactivation being the commonest genotype. They have an increased risk of
      atypia and malignancy, especially in males. 

PMID- 26205182
TI  - Bacillus Calmette-Guerin Scar Erythema: "Haloing" the Diagnosis in Kawasaki
      Disease.

PMID- 26205180
TI  - Standardization of pathologic evaluation and reporting of postneoadjuvant
      specimens in clinical trials of breast cancer: recommendations from an
      international working group.
AB  - Neoadjuvant systemic therapy is being used increasingly in the treatment of early
      stage breast cancer. Response, in the form of pathological complete response, is
      a validated and evaluable surrogate end point of survival after neoadjuvant
      therapy. Thus, pathological complete response has become a primary end point for
      clinical trials. However, there is a current lack of uniformity in the definition
      of pathological complete response. A review of standard operating procedures used
      by 28 major neoadjuvant breast cancer trials and/or 25 sites involved in such
      trials identified marked variability in specimen handling and histologic
      reporting. An international working group was convened to develop practical
      recommendations for the pathologic assessment of residual disease in neoadjuvant
      clinical trials of breast cancer and information expected from pathology reports.
      Systematic sampling of areas identified by informed mapping of the specimen and
      close correlation with radiological findings is preferable to overly exhaustive
      sampling, and permits taking tissue samples for translational research.
      Controversial areas are discussed, including measurement of lesion size,
      reporting of lymphovascular space invasion and the presence of isolated tumor
      cells in lymph nodes after neoadjuvant therapy, and retesting of markers after
      treatment. If there has been a pathological complete response, this must be
      clearly stated, and the presence/absence of residual ductal carcinoma in situ
      must be described. When there is residual invasive carcinoma, a comment must be
      made as to the presence/absence of chemotherapy effect in the breast and lymph
      nodes. The Residual Cancer Burden is the preferred method for quantifying
      residual disease in neoadjuvant clinical trials in breast cancer; other methods
      can be included per trial protocols and regional preference. Posttreatment tumor
      staging using the Tumor-Node-Metastasis system should be included. These
      recommendations for standardized pathological evaluation and reporting of
      neoadjuvant breast cancer specimens should improve prognostication for individual
      patients and allow comparison of treatment outcomes within and across clinical
      trials. 

PMID- 26205183
TI  - Parental Report of Morphine Use at Home after Pediatric Surgery.
AB  - OBJECTIVE: To describe the use of morphine at home for acute postoperative pain
      in children. STUDY DESIGN: This was a prospective, descriptive study. Patients
      less than 12 years of age who underwent surgery and who received a discharge
      prescription for morphine between January and May 2014 were included. Parents
      were given a logbook to note their use of morphine at home. A follow-up call was
      performed 3 days after discharge. The primary outcome was whether or not parents
      administered morphine according to the discharge prescription. Prescription
      filling rates, storage at home, administration devices used, and disposal of
      remaining morphine were also evaluated. RESULTS: A total of 243 subjects were
      recruited; 56% (95% CI, 46%-66%) of participants with a regular basis
      prescription administered the medication as prescribed. This number was 85% (95%
      CI, 78%-92%) in subjects receiving an as-needed prescription, including those who
      did not administer any morphine because of an absence of pain. Although 76% (95%
      CI, 68%-84%) of parents filled the morphine prescription when prescribed as
      needed, most administered two doses or less. In a subset of 77 subjects for whom
      we obtained detailed prescription data, only 9.2% of prescribed doses were
      administered. CONCLUSION: We observed that large amounts of morphine have been
      prescribed and dispensed into homes without being administered. This study
      identified a need to re-evaluate the quantity of morphine prescribed and
      dispensed after pediatric surgery.

PMID- 26205185
TI  - Serum cortisol level and disc displacement disorders of the temporomandibular
      joint.
AB  - Temporomandibular disorders (TMD) are a significant public health problem,
      affecting approximately 5-12% of the population. OBJECTIVES: This retrospective
      cross-sectional study investigated the relationship between 8 AM serum cortisol
      levels (8ASC) and disc displacement disorders (DDD) of TMD. One hundred and forty
      patients with DDD were recruited. Among them, 60 patients comprised the case
      group of disc displacement without reduction with limited opening (DDWORWLO, age
      37.7 +/- 17.22), and 80 were 'other DDD' for the control group (age 36.4 +/-
      13.08). The independent variables included domains of demography, history,
      malocclusion, comorbid symptoms, comorbid TMD and 8ASC. Data were analysed with
      the chi-square test, logistic regression and receiver operating characteristic
      (ROC) curve. Results of multiple logistic regression showed that 8ASC was the
      only factor significantly related to DDWORWLO (P = 0.006). Receiver operating
      characteristic analysis of DDWORWLO and 8ASC indicated an area under the curve of
      0.669, standard error of 0.049 and P value of 0.001. The adequate cut-off point
      of 8ASC was 12.45 (MUg dL(-1) ), with sensitivity of 0.636, and specificity of
      0.729. 8 AM serum cortisol level can be used as a clinical clue to differentiate
      DDWORWLO from other DDD.

PMID- 26205184
TI  - Phenotype and Adverse Quality of Life in Boys with Klinefelter Syndrome.
AB  - OBJECTIVES: To characterize associations among psychosocial well-being, physical
      phenotype, and sex hormones in a sample of youth with Klinefelter syndrome (KS).
      We hypothesized that KS physical traits (phenotype) are associated with adverse
      psychosocial health measures and that testosterone levels are associated with
      adverse psychosocial health. STUDY DESIGN: Forty-three boys with KS (ages 8-18
      years) participated in a cross-sectional study. Participants underwent physical
      examination, hormone analyses, and psychosocial health questionnaires. RESULTS:
      Using an investigator-developed Klinefelter Phenotype Index Scale, the number of
      KS physical traits ranged from 1-13 (mean 5.1 +/- 1.9). Pubertal boys presented
      with more KS traits compared with prepubertal boys (5.6 vs 4.2, P = .01). Boys
      diagnosed prenatally had a milder phenotype compared with those diagnosed
      postnatally. Gonadotropins were elevated without androgen deficiency in 45%.
      Psychosocial health scores indicated adverse quality of life (QOL) (67%), low
      self-esteem (38%), poor self-concept (26%), and risk for depression (16%) without
      a difference between pubertal groups. Linear regression showed that 22% of the
      variance in QOL (P = .0001) was explained by phenotype. Testosterone level was
      not associated with psychosocial health measures. CONCLUSIONS: Depending on the
      degree of phenotypic abnormality, boys with KS may be at risk for impaired QOL.
      Testosterone levels were not shown to influence psychosocial health. The
      Klinefelter Phenotype Index Scale may be a useful tool to characterize KS
      features in boys.

PMID- 26205186
TI  - Predialysis hypernatremia is a prognostic marker in acute kidney injury in need
      of renal replacement therapy.
AB  - BACKGROUND AND OBJECTIVES: The present study aimed to evaluate the prognostic
      impact of predialysis dysnatremia in patients with acute kidney injury requiring
      renal replacement therapy (RRT). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS:
      A secondary analysis of a prospective multicenter cohort study was performed.
      Serum sodium (Na) concentrations were categorized immediately before the first
      RRT as normonatremia (135<=Na <=145mEq/L), hyponatremia (mild [130<=Na
      <=134mEq/L] or severe [Na <=129mEq/L]), and hypernatremia (mild [146<=Na
      <=155mEq/L] or severe [Na >=156mEq/L]). Multivariable logistic regression was
      used to estimate the impact of sodium levels categories on hospital mortality.
      RESULTS: Dysnatremia occurred in 47.3% of 772 included patients. Hypernatremia
      was more frequent than hyponatremia (33.7% vs 13.6%, P=.001). Intensive care unit
      (ICU) and hospital mortality rates were 64.6% and 69%, respectively. Hospital
      mortality was higher in severe hypernatremia (89.1% [95% confidence interval
      {CI}, 78.7%-95.8%] vs 64.6% [CI, 59.8%-69.2%], P<.001, in normonatremia). Older
      patients, clinical admission, number of comorbidities, length of ICU stay before
      the beginning of RRT, and the number of organ dysfunctions were associated with
      higher hospital mortality. In multivariate analysis, severe hypernatremia (odds
      ratio, 2.87; 95% CI, 1.2-6.9), poor chronic heath status, severity of illness,
      sepsis, and lactate were independently associated with outcome. CONCLUSION:
      Almost 50% of patients with acute kidney injury in need of RRT in the ICU had
      mild or severe dysnatremia before dialysis initiation. Hypernatremia was the main
      sodium disturbance and independently associated with poor outcome in the study
      population.

PMID- 26205187
TI  - Prolonged pulmonary support after cardiac surgery: incidence, risk factors and
      outcomes: a retrospective cohort study.
AB  - BACKGROUND: Post-cardiac surgery pulmonary dysfunction may be underreported.
      Therefore, we evaluated associated risk factors for prolonged pulmonary support
      after cardiac surgery. METHODS AND MATERIALS: We conducted a retrospective,
      observational study of consecutive patients undergoing coronary artery bypass
      grafting or coronary artery bypass grafting plus valve repair/replacement between
      Jan 1, 2005, and Dec 31, 2010, at an academic medical center. Using multivariate
      logistic regression and Cox proportional hazards modeling, we identified risk
      factors associated with prolonged mechanical ventilation and supplemental O2
      support as well as in-hospital mortality. RESULTS: Overall, 33% (1298/3881) of
      patients required more than 2 days of mechanical ventilation and/or more than 5
      days of supplemental O2 (prolonged support). Independent risk factors included
      age, weight, pre-existing lung disease, cardiac or renal dysfunction, emergent
      status, transfusion and cardiopulmonary bypass duration. Prolonged support was
      associated with increased mortality (OR, 4.75; 95% CI, 2.95-7.95; P < .001).
      Radiological evidence of persistent pulmonary edema 2 days after surgery was
      found in 4% of controls and 27% of prolonged support cases. CONCLUSIONS: We
      identified risk factors for prolonged mechanical ventilation and supplemental O2
      use, described an association with increased adverse outcomes, and determined
      that persistent pulmonary edema on day 2 was the most likely radiological
      finding.

PMID- 26205188
TI  - [Termination of pregnancy without feticide: A French national survey].
AB  - PURPOSE: Termination of pregnancy without feticide (TOPWF) is poorly known in
      France and far less practiced than palliative care after term birth of a child
      having a lethal pathology. Few teams consider it and its practice remains
      confidential. This survey tries to describe it. MATERIAL AND METHODS: A national
      survey was realized in 2014 using a questionnaire sent to 50 centers of prenatal
      diagnosis depending on a perinatal diagnosis center in France. RESULTS: Thirty
      one centers answered the questionnaire. Seven teams shared their experience of
      TOPWF after 22-24 weeks gestation (WG). This practice concerned fetuses affected
      by "lethal" pathologies. The absence of feticide followed a parental request or a
      proposal of the medical team, after individual discussion in a multidisciplinary
      meeting. All the children born alive after TOPWF benefited of palliative care.
      The 24 other centers having answered our investigation performed systematically
      the feticide beyond 22-24 WG. They so wished "to protect" the fetus, the parents
      and the nursing team. A majority of these teams faced parental demands of
      abstention of feticide but few of them answered it favorably. CONCLUSION: A
      robust "palliative culture" seems essential to allow the nursing team to consider
      the development of TOPWF.

PMID- 26205189
TI  - Blood pressure lowering in patients with type 2 diabetes improves cardiovascular
      events including mortality, but more intensive lowering to systolic blood
      pressure less than 130 mm Hg is associated with further reduction in stroke and
      albuminuria without further reduction in cardiac events.

PMID- 26205190
TI  - Response to: Hsp27 and Hsp70 in chronic obstructive pulmonary disease.

PMID- 26205192
TI  - Prevalence and factors associated with Posttraumatic Stress Disorder seven years
      after the conflict in three districts in northern Uganda (The Wayo-Nero Study).
AB  - BACKGROUND: Research on the prevalence of Posttraumatic Stress Disorder (PTSD) is
      still limited in low income countries yet PTSD can be a public health problem in
      post conflict areas. In order to respond to the burden of PSTD in northern
      Uganda, an area that experienced civil strife for over two decades, we need
      accurate data on its (PTSD) prevalence and the associated risk factors to
      facilitate public mental health planning. METHODS: This study employed a cross
      sectional study design and data collection was undertaken in three districts in
      northern Uganda: Gulu, Amuru and Nwoya. Respondents were aged 18 years and above
      and were randomly selected at community level. A total of 2400 respondents were
      interviewed using a structured questionnaire in the three study districts. In
      this study, multivariate logistic regression was employed to analyze the
      associations of socio-demographic factors, trauma related variables and the
      outcome of PTSD. RESULTS: The prevalence of Posttraumatic Stress Disorder (PTSD)
      in the study population was 11.8 % (95 % CI: 10.5 %, 13.1 %) with a prevalence of
      10.9 % (95 % CI: 9.3 %, 12.5 %) among female respondents and 13.4 % (95 % CI:
      11.2 %, 15.7 %) among male respondents. Quite a number of factors were strongly
      associated with PTSD. Overall, a respondent had experienced 9 negative life
      events. In a multivariate logistic regression, the factors that were strongly
      associated with PTSD were: exposure to war trauma events, childhood trauma,
      negative life events, negative copying style and food insecurity. The findings
      also indicate no association between sex, age and PTSD. CONCLUSION: The
      prevalence rate of PTSD in the study communities is unacceptably high. Quite a
      number of factors were associated with PTSD. Effective public mental health
      services are needed that combine treatment (medical) psychological and social
      welfare programs especially at community level to address the high burden of
      PTSD. Longitudinal studies are also recommended to continuously assess the trends
      in PTSD in the study communities and remedial action taken.

PMID- 26205193
TI  - Structural and functional social network attributes moderate the association of
      self-rated health with mental health in midlife and older adults.
AB  - BACKGROUND: Social relationships are multifaceted, and different social network
      components can operate via different processes to influence well-being. This
      study examined associations of social network structure and relationship quality
      (positive and negative social exchanges) with mental health in midlife and older
      adults. The focus was on both direct associations of network structure and
      relationship quality with mental health, and whether these social network
      attributes moderated the association of self-rated health (SRH) with mental
      health. METHODS: Analyses were based on survey data provided by 2001 (Mean age =
      65, SD = 8.07) midlife and older adults. We used Latent Class Analysis (LCA) to
      classify participants into network types based on network structure (partner
      status, network size, contact frequency, and activity engagement), and used
      continuous measures of positive and negative social exchanges to operationalize
      relationship quality. Regression analysis was used to test moderation. RESULTS:
      LCA revealed network types generally consistent with those reported in previous
      studies. Participants in more diverse networks reported better mental health than
      those categorized into a restricted network type after adjustment for age, sex,
      education, and employment status. Analysis of moderation indicated that those
      with poorer SRH were less likely to report poorer mental health if they were
      classified into more diverse networks. A similar moderation effect was also
      evident for positive exchanges. CONCLUSIONS: The findings suggest that both
      quantity and quality of social relationships can play a role in buffering against
      the negative implications of physical health decline for mental health.

PMID- 26205194
TI  - Potential protective role of endogenous glutamate-oxaloacetate transaminase
      against glutamate excitotoxicity in fetal hypoxic-ischaemic asphyxia.
AB  - AIM: Fetal blood contains higher concentrations of glutamate-oxaloacetate
      transaminase (GOT; a blood enzyme able to metabolize glutamate) than maternal
      blood. The aim of this study was to determine the relationship between GOT and
      glutamate levels in arterial blood samples from umbilical cord in control newborn
      infants and newborn infants with hypoxic-ischaemic insult and/or symptoms of
      hypoxia-ischemia after delivery. METHOD: A total of 46 newborn infants (28
      females, 18 males) were prospectively included in the study. Twenty-three infants
      (18 females, five males) were included as control participants and 23 (10
      females, 13 males) were included as newborn infants at risk of adverse
      neurological outcome (defined as umbilical blood with pH <7.1). RESULTS: Analysis
      of glutamate concentration and GOT activity in umbilical blood samples showed
      that newborn infants with pH <7.1 had higher levels of glutamate (142.4 MUmol/L
      [SD 61.4] vs 62.8 MUmol/L [SD 25.5]; p<0.001) and GOT (83.1 U/L [SD 60.9] vs 34.9
      U/L [SD 18.2]; p<0.001) compared to newborn infants without fetal distress.
      Analysis of Apgar scores and blood pH values (markers of perinatal distress)
      showed that conditions of severe distress were associated with higher glutamate
      and GOT levels. INTERPRETATION: During fetal development, the ability of GOT to
      metabolize glutamate suggests that this enzyme can act as an endogenous
      protective mechanism in the control of glutamate homeostasis.

PMID- 26205191
TI  - EGFR targeted therapies and radiation: Optimizing efficacy by appropriate drug
      scheduling and patient selection.
AB  - The epidermal growth factor receptor (EGFR) plays an important role in tumor
      progression and treatment resistance for many types of malignancies including
      head and neck, colorectal, and nonsmall cell lung cancer. Several EGFR targeted
      therapies are efficacious as single agents or in combination with chemotherapy.
      Given the toxicity associated with chemoradiation and poor outcomes seen in
      several types of cancers, combinations of EGFR targeted agents with or without
      chemotherapy have been tested in patients receiving radiation. To date, the only
      FDA approved use of an anti-EGFR therapy in combination with radiation therapy is
      for locally advanced head and neck cancer. Given the important role EGFR plays in
      lung and colorectal cancer and the benefit of EGFR inhibition combined with
      chemotherapy in these disease sites, it is perplexing why EGFR targeted therapies
      in combination with radiation or chemoradiation have not been more successful. In
      this review we summarize the clinical findings of EGFR targeted therapies
      combined with radiation and chemoradiation regimens. We then discuss the
      interaction between EGFR and radiation including radiation induced EGFR
      signaling, the effect of EGFR on DNA damage repair, and potential mechanisms of
      radiosensitization. Finally, we examine the potential pitfalls with scheduling
      EGFR targeted therapies with chemoradiation and the use of predictive biomarkers
      to improve patient selection. 

PMID- 26205195
TI  - Insights from the computational studies on the oxidized as-isolated state of
      [NiFeSe] hydrogenase from D. vulgaris Hildenborough.
AB  - A density functional theory study of the active site structure and features of
      the oxygen tolerant [NiFeSe] Hase in the oxidized as-isolated state of the enzyme
      D. vulgaris Hildenborough (DvH) is reported here. The three conformers reported
      to be present in the X-ray structure (PDB ID: ) have been studied. The novel
      bidentate interchalcogen ligand (S-Se) in Conf-I of the [NiFeSe] Hase reported
      for the first time in hydrogenases (Hase) is found to be of donor-acceptor type
      with an uneven eta(2) L -> M sigma-bond. The symmetry mismatch at the sp orbital
      of Se and at the dz(2) orbital of Ni has been identified to be the reason for the
      inability of Conf-II to convert to Conf-I. NBO analysis shows that the sulfinate
      ligand peculiar to the state stabilizes the active site through n ->pi*
      interactions. The results reveal that the isolated oxidized state of the [NiFeSe]
      Hase is significantly different from the well-known [NiFe] Hase. 

PMID- 26205196
TI  - [Snowman sign].

PMID- 26205197
TI  - [Oral communications presented during the 71st meeting of the SNFMI (Besancon,
      June 10-12, 2015)].

PMID- 26205198
TI  - Structural Requirements of Some 2-(1-Propylpiperidin-4-yl)-1H-benzimidazole-4
      carboxamide Derivatives as Poly (ADP-Ribose) Polymerase (PARP) for the Treatment
      of Cancer: QSAR Approach.
AB  - The present study is aimed to elucidate the structural features of substituted 2
      (1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide required for poly (ADP
      ribose) polymerase inhibition and to obtain predictive 2D QSAR models to guide
      the rational synthesis of novel poly (ADP-ribose) polymerase inhibitors. The
      statistical analysis has shown that excellent results are obtained by using
      partial least regression based on simulated annealing method. The best model was
      selected based on the highest correlation coefficient r (2) = 0.8590, and cross
      validated squared correlation coefficient q (2) = 0.7875 with external predictive
      ability of [Formula: see text] was developed by stepwise PLS method with the
      descriptors like T_N_F_1, SdsCHcount, and Rotatable Bond Count. The generated
      models provide insight into the influence of various interactive fields on the
      activity and, thus, can help in designing and forecasting the inhibition activity
      of novel (ADP-ribose) polymerase molecules. 

PMID- 26205200
TI  - The resisted rise of randomisation in experimental design: British agricultural
      science, c.1910-1930.
AB  - The most conspicuous form of agricultural experiment is the field trial, and
      within the history of such trials, the arrival of the randomised control trial
      (RCT) is considered revolutionary. Originating with R.A. Fisher within British
      agricultural science in the 1920s and 1930s, the RCT has since become one of the
      most prodigiously used experimental techniques throughout the natural and social
      sciences. Philosophers of science have already scrutinised the epistemological
      uniqueness of RCTs, undermining their status as the 'gold standard' in
      experimental design. The present paper introduces a historical case study from
      the origins of the RCT, uncovering the initially cool reception given to this
      method by agricultural scientists at the University of Cambridge and the
      (Cambridge based) National Institute of Agricultural Botany. Rather than giving
      further attention to the RCT, the paper focuses instead on a competitor method
      the half-drill strip-which both predated the RCT and remained in wide use for at
      least a decade beyond the latter's arrival. In telling this history, John
      Pickstone's Ways of Knowing is adopted, as the most flexible and productive way
      to write the history of science, particularly when sciences and scientists have
      to work across a number of different kinds of place. It is shown that those who
      resisted the RCT did so in order to preserve epistemic and social goals that
      randomisation would have otherwise run a tractor through. 

PMID- 26205199
TI  - Colonization history shaped the immunity of the western house mouse.
AB  - The general development of immune response in the short and long term is a
      product of the antigenic environment in which a species resides. Colonization of
      a novel antigenic environment by a species would be expected to alter the immune
      system. Animals that successfully adapt their immune responses will successfully
      colonize new locations. However, founder events associated with colonization by
      limited numbers of individuals from a source population will constrain
      adaptability. How these contradicting forces shape immunity in widely distributed
      species is unknown. The western house mouse (Mus musculus domesticus) spread
      globally from the Indo-Pakistani cradle, often in association with human
      migration and settlement. In the present study, we tested the hypothesis that
      wild-derived outbred laboratory populations of house mice from their original
      range (Iran) and historically recent European invasive populations (from France
      and Germany) present differences in immune functional diversity corresponding to
      recent historical founder events in Europe and movement to novel antigenic
      environments. We found that (1) European mice had lower total white blood cell
      (WBC) counts but higher immunoglobulin E concentrations than their Iranian
      counterparts, and (2) there were no significant differences in the measured
      immunological parameters among European populations. The results indicate that
      founder events in European mice and selection pressure exerted by the composition
      of local parasitic helminth communities underlie the observed patterns. 

PMID- 26205201
TI  - Animal breeding in the age of biotechnology: the investigative pathway behind the
      cloning of Dolly the sheep.
AB  - This paper addresses the 1996 cloning of Dolly the sheep, locating it within a
      long-standing tradition of animal breeding research in Edinburgh. Far from being
      an end in itself, the cell-nuclear transfer experiment from which Dolly was born
      should be seen as a step in an investigative pathway that sought the production
      of medically relevant transgenic animals. By historicising Dolly, I illustrate
      how the birth of this sheep captures a dramatic redefinition of the life
      sciences, when in the 1970s and 1980s the rise of neo-liberal governments and the
      emergence of the biotechnology market pushed research institutions to show
      tangible applications of their work. Through this broader interpretative
      framework, the Dolly story emerges as a case study of the deep transformations of
      agricultural experimentation during the last third of the twentieth century. The
      reorganisation of laboratory practice, human resources and institutional settings
      required by the production of transgenic animals had unanticipated consequences.
      One of these unanticipated effects was that the boundaries between animal and
      human health became blurred. As a result of this, new professional spaces emerged
      and the identity of Dolly the sheep was reconfigured, from an instrument for
      livestock improvement in the farm to a more universal symbol of the new cloning
      age. 

PMID- 26205202
TI  - Charting the history of agricultural experiments.
AB  - Agricultural experimentation is a world in constant evolution, spanning multiple
      scientific domains and affecting society at large. Even though the questions
      underpinning agricultural experiments remain largely the same, the instruments
      and practices for answering them have changed constantly during the twentieth
      century with the advent of new disciplines like molecular biology, genomics,
      statistics, and computing. Charting this evolving reality requires a mapping of
      the affinities and antinomies at work within the realm of agricultural research,
      and a consideration of the practices, tools and social and political structures
      in which agricultural experiments are grounded. Three main questions will be
      addressed to provide an overview of the complex world of agricultural research
      investigated by the special issue: What is an agricultural experiment? Who is an
      experimenter in agriculture? Where do agricultural experiments take place? It
      will become apparent that agricultural experiments have a wide relevance for
      human development as they touch upon concerns related to human health and
      nutrition, contribute to policy discussions, and can affect the social and
      political structures in which farming is embedded. 

PMID- 26205203
TI  - The Third Man: comparative analysis of a science autobiography and a cinema
      classic as windows into post-war life sciences research.
AB  - In 2003, biophysicist and Nobel Laureate Maurice Wilkins published his
      autobiography entitled The Third Man. In the preface, he diffidently points out
      that the title (which presents him as the 'third' man credited with the co
      discovery of the structure of DNA, besides Watson and Crick) was chosen by his
      publisher, as a reference to the famous 1949 movie no doubt, featuring Orson
      Welles in his classical role as penicillin racketeer Harry Lime. In this paper I
      intend to show that there is much more to this title than merely its familiar
      ring. If subjected to a (psychoanalytically inspired) comparative analysis,
      multiple correspondences between movie and memoirs can be brought to the fore.
      Taken together, these documents shed an intriguing light on the vicissitudes of
      budding life sciences research during the post-war era. I will focus my
      comparative analysis on issues still relevant today, such as dual use, the
      handling of sensitive scientific information (in a moral setting defined by the
      tension between collaboration and competition) and, finally, on the
      interwovenness of science and warfare (i.e. the 'militarisation' of research and
      the relationship between beauty and destruction). Thus, I will explain how
      science autobiographies on the one hand and genres of the imagination (such as
      novels and movies) on the other may deepen our comprehension of tensions and
      dilemmas of life sciences research then and now. For that reason, science
      autobiographies can provide valuable input (case material) for teaching
      philosophy and history of science to science students. 

PMID- 26205204
TI  - Is synthetic biology mechanical biology?
AB  - A widespread and influential characterization of synthetic biology emphasizes
      that synthetic biology is the application of engineering principles to living
      systems. Furthermore, there is a strong tendency to express the engineering
      approach to organisms in terms of what seems to be an ontological claim:
      organisms are machines. In the paper I investigate the ontological and heuristic
      significance of the machine analogy in synthetic biology. I argue that the use of
      the machine analogy and the aim of producing rationally designed organisms does
      not necessarily imply a commitment to mechanical biology. The ideal of applying
      engineering principles to biology is best understood as expressing recognition of
      the machine-unlikeness of natural organisms and the limits of human cognition.
      The paper suggests an interpretation of the identification of organisms with
      machines in synthetic biology according to which it expresses a strategy for
      representing, understanding, and constructing living systems that are more
      machine-like than natural organisms. 

PMID- 26205205
TI  - The function of repeating: The relation between word class and repetition type in
      developmental stuttering.
AB  - BACKGROUND: It is already known that preschool-age children who stutter (CWS)
      tend to stutter on function words at the beginning of sentences. It is also known
      that phonological errors potentially resulting in part-word repetitions tend to
      occur on content words. However, the precise relation between word class and
      repetition type in preschool-age stuttering is unknown. AIMS: To investigate
      repetitions associated with monosyllabic words in preschool-age CWS.
      Specifically, it was hypothesized that repetition type should vary according to
      word class in preschool-age CWS and children who do not stutter (CWNS). METHODS &
      PROCEDURES: Thirteen preschool-age CWS and 15 preschool-age CWNS produced age
      appropriate narratives, which were transcribed and coded for part-word
      repetitions (PWR) and whole-word repetitions (WWR) occurring on monosyllabic
      words. Each repetition type was also coded for word class (i.e., function versus
      content). OUTCOMES & RESULTS: Results indicated that although CWS and CWNS were
      significantly more likely to produce PWR on content words, this tendency did not
      differ between the two talker groups. Further, CWS and CWNS did not differ in
      their tendencies to produce PWR versus WWR overall, but the tendency to produce
      repetitions on function words was significantly greater for CWS versus CWNS.
      CONCLUSIONS & IMPLICATIONS: Findings are taken to suggest that repetitions of
      monosyllabic words in young children are not easily explained from the
      perspective of phonological errors, but may instead be considered from an
      incremental planning of speech perspective.

PMID- 26205206
TI  - Novosphingobium aquaticum sp. nov., isolated from lake water in Suwon, Republic
      of Korea.
AB  - A novel Gram-stain negative, yellow coloured, strictly aerobic, rod-shaped, non
      motile bacterium designated as THW-SA1(T), was isolated from lake water near
      Samsung apartment, Suwon, Republic of Korea. The phylogenetic analysis based on
      16S rRNA gene sequences showed that strain THW-SA1(T) belongs to the genus
      Novosphingobium and is closely related to Novosphingobium taihuense (97.8 %) and
      Novosphingobium subterraneum (97.1 %). The DNA-DNA relatedness values between
      strain THW-SA1(T) and the most closely related type strains were found to be less
      than 30.0 %. The DNA G+C content was determined to be 67.5 mol%. The strain grows
      optimally at 25-28  degrees C, at pH 7.0, and in the presence of 0.5 % NaCl. The
      predominant isoprenoid quinone was identified as ubiquinone Q-10. The polar lipid
      profile comprises diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, phosphatidyldimethylethanolamine, sphingoglycolipid,
      phosphatidylcholine, some unidentified phospholipids and some unidentified polar
      lipids. Fatty acids characteristic for this genus, such as C16:1, C14:0 2-OH,
      C16:1 omega6c and/or C16:1 omega7c (summed feature 3) and C18:1 omega6c and/or
      C18:1 omega7c (summed feature 8) were also detected. On the basis of the
      phenotypic and genotypic analysis, the strain THW-SA1(T) is considered to
      represent a novel species of the genus Novosphingobium, for which the name
      Novosphingobium aquaticum sp. nov. is proposed. The type strain is THW-SA1(T)
      (=KCTC 42608(T)=CCTCC AB 2015114(T)).

PMID- 26205207
TI  - Sinomonas halotolerans sp. nov., an actinobacterium isolated from a soil sample.
AB  - A novel actinobacterial strain, designated CFH S0499(T), was isolated from a soil
      sample collected from Catba island in Halong Bay, Vietnam. The cells were
      observed to be Gram-stain positive, aerobic, non-motile, curved rods. The strain
      was found to grow optimally at 28  degrees C and pH 7.0. Growth was found to
      occur at 0-7 % NaCl. Chemotaxonomically, the peptidoglycan type was determined to
      be of the A3alpha type, with glutamic acid, glycine, alanine and lysine as the
      major cell wall amino acids. The whole cell sugars were found to contain mannose,
      galactose, glucose, ribose and rhamnose. The polar lipids were identified as
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, glycolipids
      and two unidentified phospholipids. The major fatty acids were identified as
      anteiso-C15:0, iso-C15:0, anteiso-C17:0 and iso-C16:0 and the predominant
      respiratory quinone as MK-9 (H2), with a minor amount of MK-10 (H4) and MK-8
      (H2). The G+C content of the genomic DNA was determined to be 71.8 mol%. The 16S
      rRNA gene sequence analysis showed that strain CFH S0499(T) should be assigned to
      the genus Sinomonas and is closely related to members of the species Sinomonas
      atrocyanea DSM 20127(T) (98.3 %), Sinomonas soli CW 59(T) (98.28 %), Sinomonas
      flava CW 108(T) (98.26 %), Sinomonas mesophila MPLK 26(T) (97.5 %) and Sinomonas
      notoginsengisoli SYP-B 575(T) (95.8 %). DNA-DNA hybridizations showed low values
      (49.1-54.5 %) between strain CFH S0499(T) and its four closest neighbours. Based
      on phenotypic, chemotaxonomic and phylogenetic analysis, strain CFH S0499(T) is
      concluded to represent a novel species of the genus Sinomonas, for which the name
      Sinomonas halotolerans sp. nov. is proposed, with CFH S0499(T) as the type strain
      (=CCTCC AB2014300(T) = KCTC 39116(T)).

PMID- 26205208
TI  - Assessing the effectiveness of specially protected areas for conservation of
      Antarctica's botanical diversity.
AB  - Vegetation is sparsely distributed over Antarctica's ice-free ground, and
      distinct plant communities are present in each of the continent's 15 recently
      identified Antarctic Conservation Biogeographic Regions (ACBRs). With rapidly
      increasing human activity in Antarctica, terrestrial plant communities are at
      risk of damage or destruction by trampling, overland transport, and
      infrastructure construction and from the impacts of anthropogenically introduced
      species, as well as uncontrollable pressures such as fur seal (Arctocephalus
      gazella) activity and climate change. Under the Protocol on Environmental
      Protection to the Antarctic Treaty, the conservation of plant communities can be
      enacted and facilitated through the designation of Antarctic Specially Protected
      Areas (ASPAs). We examined the distribution within the 15 ACBRs of the 33 ASPAs
      whose explicit purpose includes protecting macroscopic terrestrial flora. We
      completed the first survey using normalized difference vegetation index (NDVI)
      satellite remote sensing to provide baseline data on the extent of vegetation
      cover in all ASPAs designated for plant protection in Antarctica. Large omissions
      in the protection of Antarctic botanical diversity were found. There was no
      protection of plant communities in 6 ACBRs, and in another 6, <0.4% of the ACBR
      area was included in an ASPA that protected vegetation. Protected vegetation
      cover within the 33 ASPAs totaled 16.1 km(2) for the entire Antarctic continent;
      over half was within a single protected area. Over 96% of the protected
      vegetation was contained in 2 ACBRs, which together contributed only 7.8% of the
      continent's ice-free ground. We conclude that Antarctic botanical diversity is
      clearly inadequately protected and call for systematic designation of ASPAs
      protecting plant communities by the Antarctic Treaty Consultative Parties, the
      members of the governing body of the continent. 

PMID- 26205209
TI  - Method for Controlling Electrical Properties of Single-Layer Graphene Nanoribbons
      via Adsorbed Planar Molecular Nanoparticles.
AB  - A simple method for fabricating single-layer graphene nanoribbons (sGNRs) from
      double-walled carbon nanotubes (DWNTs) was developed. A sonication treatment was
      employed to unzip the DWNTs by inducing defects in them through annealing at 500 
      degrees C. The unzipped DWNTs yielded double-layered GNRs (dGNRs). Further
      sonication allowed each dGNR to be unpeeled into two sGNRs. Purification
      performed using a high-speed centrifuge ensured that more than 99% of the formed
      GNRs were sGNRs. The changes induced in the electrical properties of the obtained
      sGNR by the absorption of nanoparticles of planar molecule, naphthalenediimide
      (NDI), were investigated. The shape of the I-V curve of the sGNRs varied with the
      number of NDI nanoparticles adsorbed. This was suggestive of the existence of a
      band gap at the narrow-necked part near the NDI-adsorbing area of the sGNRs. 

PMID- 26205211
TI  - Therapeutic potential of resveratrol in heart failure.
AB  - Despite existing therapies, patients with heart failure have a very poor quality
      of life and a high 1-year mortality rate. Given the impact of this syndrome on
      health outcomes, research is being directed toward identifying novel strategies
      to treat heart failure symptoms as well as to prolong survival. One molecule that
      has been tested in animal models for this purpose is resveratrol. Resveratrol is
      a naturally occurring polyphenol found in several plants, and administration of
      resveratrol has been shown to prevent and/or slow the progression of heart
      failure in animal models of heart failure induced by myocardial infarction,
      pressure overload, myocarditis, and chemotherapy-induced cardiotoxicity. In
      addition, some animal studies have shown that resveratrol improves cardiac
      function and survival when administered as a treatment for established heart
      failure. Furthermore, as heart failure induces alterations in skeletal muscle and
      vasculature that also contribute to certain heart failure symptoms, such as
      fatigue and exercise intolerance, it has also been shown that resveratrol acts on
      these peripheral tissues to improve skeletal muscle and endothelial/vascular
      function. Therefore, if these animal studies translate to humans, resveratrol may
      prove to be a novel therapy for the treatment of heart failure. 

PMID- 26205210
TI  - Dopamine D2-Like Receptors and Behavioral Economics of Food Reinforcement.
AB  - Previous studies suggest dopamine (DA) D2-like receptor involvement in the
      reinforcing effects of food. To determine contributions of the three D2-like
      receptor subtypes, knockout (KO) mice completely lacking DA D2, D3, or D4
      receptors (D2R, D3R, or D4R KO mice) and their wild-type (WT) littermates were
      exposed to a series of fixed-ratio (FR) food-reinforcement schedules in two
      contexts: an open economy with additional food provided outside the experimental
      setting and a closed economy with all food earned within the experimental
      setting. A behavioral economic model was used to quantify reinforcer
      effectiveness with food pellets obtained as a function of price (FR schedule
      value) plotted to assess elasticity of demand. Under both economies, as price
      increased, food pellets obtained decreased more rapidly (ie, food demand was more
      elastic) in DA D2R KO mice compared with WT littermates. Extinction of responding
      was studied in two contexts: by eliminating food deliveries and by delivering
      food independently of responding. A hyperbolic model quantified rates of
      extinction. Extinction in DA D2R KO mice occurred less rapidly compared with WT
      mice in both contexts. Elasticity of food demand was higher in DA D4R KO than WT
      mice in the open, but not closed, economy. Extinction of responding in DA D4R KO
      mice was not different from that in WT littermates in either context. No
      differences in elasticity of food demand or extinction rate were obtained in D3R
      KO mice and WT littermates. These results indicate that the D2R is the primary DA
      D2-like receptor subtype mediating the reinforcing effectiveness of food. 

PMID- 26205212
TI  - Why we shouldn't normalise the use of e-cigarettes.

PMID- 26205213
TI  - Positioning Trocars for Performing Sleeve Gastrectomy: the right side or between
      the legs of the patient?

PMID- 26205214
TI  - Outcome of Laparoscopic Gastric Bypass (LRYGB) with a Program for Enhanced
      Recovery After Surgery (ERAS).
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) programs are well established
      for patients undergoing colorectal surgery. Relatively little is known about ERAS
      following bariatric surgery in general or following laparoscopic Roux-en-Y
      gastric bypass (LRYGB) in particular. PATIENTS AND METHODS: This is a
      prospective, observational study of 388 consecutive patients that underwent LRYGB
      with ERAS in a general hospital. The ERAS protocol included standardizations of
      pre-, intra-, and postoperative modalities in order to reduce the stress response
      of the patients. Primary outcome measures were length of stay (LOS),
      postoperative morbidity, readmissions, and reoperations. RESULTS: Mean (SD)
      baseline body mass index (BMI) and age was 46.4 (6.7) kg/m(2) and 45.1 (11.2)
      years, respectively. Fifty-four percent of the patients were on medication for
      hypertension (HT) and 38 % for type 2 diabetes mellitus (DM2). Mean (SD) and
      median (range) surgical time was 73.8 (16.9) and 65 (40-143) min, respectively.
      Mean LOS was 1.3 days (1.1), median 1 day (1-14). Of all patients, 322 (83 %)
      were discharged on the first postoperative day (POD). Overall morbidity was 9.8
      %. Three patients (0.8 %) had life-threatening complications. The readmission
      rate was 4.9 %, and 3.4 % of the patients had to be reoperated. With a follow-up
      rate of 83 % at 1 year, total weight loss (TWL) was 31 % and excess BMI loss
      (EBMIL) 70 %. Total remission of DM2 and HT was achieved in 70 and 42 % of the
      patients, respectively. CONCLUSION: Enhanced recovery following LRYGB with ERAS
      programs is possible and safe even in a low volume, general hospital. Early
      discharge does not increase postoperative morbidity or readmissions.

PMID- 26205215
TI  - Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve
      Gastrectomy: a 1-year Follow-up.
AB  - BACKGROUND: Roux-en-Y gastric bypass (GBP) and sleeve gastrectomy (SG) have
      increased dramatically, potentially increasing the prevalence of nutritional
      deficiencies. The aim of this study was to analyze the effects of food
      restriction during the first year after bariatric surgery (BS) on nutritional
      parameters. METHODS: Twenty-two and 30 obese patients undergoing GBP and SG were
      prospectively followed at baseline and 3, 6, and 12 months after BS (N = 14 and N
      = 19 at T12). We evaluated food intake and nutrient adequacy (T0, T3, T12), as
      well as serum vitamin and mineral concentration (T0, T3, T6, T12). RESULTS: At
      baseline, GBP and SG patients had similar clinical characteristics, food intake,
      nutrient adequacy, and serum concentration. The drastic energy and food reduction
      led to very low probabilities of adequacy for nutrients similar in both models
      (T3, T12). Serum analysis demonstrated a continuous decrease in prealbumin during
      the follow-up, indicating mild protein depletion in 37 and 38% of GBP patients
      and 57 and 52% of SG patients, respectively, at T3 and T12. Conversely, despite
      the low probabilities of adequacy observed at T3 and T12, systematic multivitamin
      and mineral supplementation after GBP and SG prevented most nutritional
      deficiencies. CONCLUSIONS: GBP and SG have comparable effects in terms of energy
      and food restriction and subsequent risk of micronutrient and protein
      deficiencies in the first year post BS. Such results advocate for a cautious
      monitoring of protein intake after GPB and SG and a systematic multivitamin and
      mineral supplementation in the first year after SG.

PMID- 26205216
TI  - Duodenal-Jejunal Bypass Surgery Ameliorates Glucose Homeostasis and Reduces
      Endoplasmic Reticulum Stress in the Liver Tissue in a Diabetic Rat Model.
AB  - BACKGROUND: Duodenal-jejunal bypass (DJB) has been shown to be an effective
      surgical treatment for type 2 diabetes mellitus (T2DM). However, the underlying
      mechanisms are poorly understood. Recently, accumulating evidences suggest that
      endoplasmic reticulum (ER) stress plays an important role in the development of
      insulin resistance in T2DM. The present study was designed to investigate the
      effect of DJB on glucose homeostasis, the ER stress state in the liver tissue,
      and the involving signaling independently of weight loss. METHODS: Thirty adult
      male T2DM Sprague-Dawley (SD) rats induced by high-fat diet and low dose of
      streptozotocin (STZ) were randomly divided into DJB and sham groups. Ten age
      matched male SD rats were assigned as the control group. The parameters of body
      weight and calorie intake were measured at indicated time points. The glucose
      tolerance and insulin resistance were detected to evaluate the glucose
      homeostasis. Serum insulin was determined by enzyme-linked immunosorbent assay
      (ELISA). The markers of ER stress, the activity of c-Jun N-terminal kinase (JNK)
      and serine phosphorylation of insulin receptor substrate 1 (IRS-1) in the liver
      tissue, were determined by Western blotting. RESULTS: DJB induced significant
      improvements in glucose homeostasis and insulin sensitivity, but without weight
      loss. DJB improved the ER stress state indicated by decreased protein kinase RNA
      (PKR)-like ER protein kinase (PERK) and inositol-requiring enzyme 1 (IRE-1)
      phosphorylation in the liver tissue. The JNK activity and serine phosphorylation
      of IRS-1 in the liver tissue were significantly reduced after DJB. CONCLUSIONS:
      DJB ameliorates glucose homeostasis. Meanwhile, our study helps to reveal that
      the reduced hepatic ER stress and the decreased JNK activity may contribute to
      the improved glucose homeostasis after DJB.

PMID- 26205217
TI  - Conversion of Open Vertical Banded Gastroplasty to Roux-en-Y Gastric Bypass: a
      Single-Center, Single-Surgeon Experience with 6 Years of Follow-up.
AB  - BACKGROUND: The aim of this study is to assess feasibility, relief of
      complications and mid- and long-term weight loss results following the conversion
      of open vertical banded gastroplasty (VBG) to Roux-en-Y gastric bypass (RYGB).
      MATERIALS AND METHODS: Retrospective analysis of patients undergoing conversion
      of open VBG to RYGB (open and laparoscopic) between 1 April 2000 and 1 January
      2015 was performed. (Post)operative complications were listed. Weight loss was
      assessed using excess weight (EW), percentage excess weight loss (%EWL) and body
      mass index (BMI) at 1-year intervals after surgery. Ideal weight was determined
      by recalculating individual lengths to a BMI of 25 kg/m(2). Application of
      polynomial regression models was used to quantify weight loss over time. RESULTS:
      Ninety patients were identified in the database. Mean time between bariatric
      interventions was 9.6 years. Reasons for conversion were insufficient weight loss
      (82.2%) and outlet obstruction (17.8%). Early complications were encountered in
      eight patients of which three were reoperated. Patients who underwent conversion
      for inadequate weight loss after VBG were retrospectively analyzed regarding
      weight loss: 78.0% EWL after 1 year, 71.4% after 2 years, 62.1% after 3 years,
      64.1% after 4 years, 70.2% after 5 years, and 68.9% after 6 years. Outlet
      obstruction was relieved in 94%. Patient satisfaction was assessed by telephone:
      86.4% would repeat the conversion. CONCLUSIONS: Conversion of open VBG to RYGB is
      feasible and safe and can be performed with an acceptable complication rate. It
      gives excellent weight loss results and relief of outlet obstruction.

PMID- 26205219
TI  - Correction to Transcription Factor Sensor System for Parallel Quantification of
      Metabolites On-Chip.

PMID- 26205218
TI  - Prediction of Diabetes Remission in Morbidly Obese Patients After Roux-en-Y
      Gastric Bypass.
AB  - BACKGROUND: Morbidly obese patients with type 2 diabetes have shown significant
      improvement in glycemic control after Roux-en-Y gastric bypass (RYGB). This study
      aimed to elucidate the predictors of diabetes remission. METHODS: A retrospective
      review of a prospectively established database identified 134 type 2 diabetes
      patients who underwent laparoscopic RYGB between January 2011 and February 2014.
      Partial and complete remission of diabetes was defined as glycated hemoglobin
      (HbA1c) level <6.5 and <6.0%, respectively, without the use of antidiabetic
      medication. Pre- and postoperative clinical outcomes were compared between the
      remission and non-remission groups to identify the predictors of partial or
      complete remission of diabetes. RESULTS: The mean duration of diabetes and
      preoperative HbA1c level were 4.6 years and 8.0%, respectively. The body mass
      index (BMI) of the enrolled patients decreased from 37.9 to 28.8 kg/m(2) during
      the mean follow-up of 12.3 months; 61.8% of the patients achieved partial or
      complete remission of diabetes. Multivariate analysis revealed that age at
      operation (odds ratio [OR] = 0.880; 95% confidence interval [CI] 0.807-0.960),
      HbA1c level (OR = 0.527; 95% CI 0.325-0.854), and C-peptide level (OR = 1.463;
      95% CI 1.054-2.029) in the preoperative laboratory study, and the percentage of
      total weight loss (%TWL) (OR = 1.186; 95% CI 1.072-1.313) after RYGB were the
      independent predictors of partial or complete diabetes remission. CONCLUSION: The
      predictive factors for diabetes remission after RYGB include age at operation,
      HbA1c and C-peptide levels, and the %TWL after surgery.

PMID- 26205220
TI  - T-cell receptor activation of human CD4(+) T cells shifts the innate TLR response
      from CXCL8(hi) IFN-gamma(null) to CXCL8(lo) IFN-gamma(hi).
AB  - Toll-like receptors (TLRs) play a major part in providing innate immunity against
      pathogenic microorganisms. Recent studies show that these receptors are also
      expressed on T cells, which are the sentinels of adaptive immunity. Here, we have
      investigated the regulatory role of the T-cell receptor in the functioning of
      these innate receptors in T cells. We show that freshly isolated human CD4(+) T
      cells readily secrete the neutrophil chemoattractant CXCL8 upon activation with
      the TLR ligands Pam3CSK and flagellin. In contrast, TCR-activated cells secrete
      considerably less CXCL8 but start producing IFN-gamma upon stimulation with TLR
      agonists in the absence of concomitant TCR engagement. These T cells show
      increased activation of p38 and JNK MAP-kinases in response to TLR stimulation,
      and inhibition of p38 abrogates TLR-induced IFN-gamma secretion. The shifting of
      the T-cell innate immune response from CXCL8(hi) IFN-gamma(null) in freshly
      isolated to CXCL8(lo) IFN-gamma(hi) in activated T cells is also observed in
      response to endogenous innate stimulus, IL-1. These results suggest that the
      innate immune response of human CD4(+) T cells switches from a proinflammatory to
      an effector type following activation of these cells through the antigen
      receptor.

PMID- 26205221
TI  - Anti-Human H1N1pdm09 and swine H1N1 Virus Antibodies among Swine Workers in
      Guangdong Province, China.
AB  - To assess the potential transmission for zoonotic influenza, sero-antibodies
      against two kinds of influenza viruses--classical swine H1N1 and human H1N1pdm09
      virus were detected in persons whose profession involved contact with swine in
      Guangdong province, China. Compared to the non-exposed control group, a
      significantly higher proportion of subjects with occupational contact to pigs
      exhibited positive seroreaction against the classical H1N1 SIV. Participants aged
      26-50 years were at high risk of classic swine H1N1 infections. Seropositive rate
      to 2009 pandemic H1N1 virus among swine workers was similar with controls. The
      major impact of age was apparent for younger populations. Our present study has
      documented evidence for swine influenza virus infection among persons with
      occupational swine exposures. The differences of seroreactivity for the two
      tested influenza subtypes emphasize the necessity of regular surveillance both in
      pigs and human.

PMID- 26205222
TI  - Predictive Equations Are Inaccurate in the Estimation of the Resting Energy
      Expenditure of Children With End-Stage Liver Disease.
AB  - BACKGROUND AND OBJECTIVES: Malnutrition is common in children with end-stage
      liver disease (ESLD) and is associated with increased morbidity and mortality.
      The inability to accurately estimate energy needs of these patients may
      contribute to their poor nutrition status. In clinical practice, predictive
      equations are used to calculate resting energy expenditure (cREE). The objective
      of this study is to assess the accuracy of commonly used equations in pediatric
      patients with ESLD. METHODS: Retrospective study performed at the Hospital for
      Sick Children. Clinical, laboratory, and indirect calorimetry data from children
      listed for liver transplant between February 2013 and December 2014 were
      reviewed. Calorimetry results were compared with cREE estimated using the Food
      and Agriculture Organization/World Health Organization/United Nations University
      (FAO/WHO/UNU), Schofield [weight], and Schofield [weight and height] equations.
      RESULTS: Forty-five patients were included in this study. The median age was 9
      months, and the most common indication for transplantation was biliary atresia
      (64%). The Schofield [weight and height], FAO/WHO/UNU, and Schofield [weight]
      equations were compared with indirect calorimetry and found to have a mean (SD)
      difference of 48.8 (344.0), 59.3 (229.8), and 206.5 (502.6) kcal/d, respectively.
      The FAO/WHO/UNU, Schofield [weight], and Schofield [weight and height] equations
      introduced a mean error of 21%, 38%, and 76%, respectively. The FAO/WHO/UNU
      equation tended to underestimate, whereas the Schofield equations overestimated
      the REE. CONCLUSIONS: Commonly used predictive equations perform poorly in
      infants and young children with ESLD. Indirect calorimetry should be used when
      available to guide energy provision, particularly in children who are already
      malnourished.

PMID- 26205223
TI  - Effects of experimentally increased in ovo lysozyme on egg hatchability, chicks
      complement activity, and phenotype in a precocial bird.
AB  - In birds, spectrum of egg white proteins deposited into the egg during its
      formation are thought to be essential maternal effects. Particularly, egg white
      lysozyme (LSM), exhibiting great between and within species variability, is
      considered to be essential for developing avian embryos due to its physiological,
      antimicrobial, and innate immune defense functions. However, there have been few
      studies investigating effects of LSM on early post-hatching phenotype, despite
      its broad physiological and protective role during embryogenesis. Here, we test
      how experimentally increased concentrations of egg white LSM affect hatchability
      in Japanese quail (Coturnix japonica) and chick phenotype immediately after
      hatching (particularly body weight, tarsus length, plasma LSM concentration, and
      plasma complement activity). Chicks from eggs with increased LSM concentration
      displayed reduced tarsus length compared to chicks from control eggs while
      hatchability, body weight and plasma LSM concentration were unaffected. It is
      worth noting that no effect of increased in ovo lysozyme on eggs hatchability
      could be related to pathogen-free environment during artificial incubation of
      experimental eggs causing minimal pressure on embryo viability. While tangible in
      vivo mechanisms during avian embryogenesis remain to be tested, our study is the
      first to document experimentally that egg white LSM appears to have growth
      regulation role during embryo development, with possible underlying phenotypic
      consequences in the early post-hatching period in precocial birds.

PMID- 26205228
TI  - Extraction and preconcentration of formaldehyde in water by polypyrrole-coated
      magnetic nanoparticles and determination by high-performance liquid
      chromatography.
AB  - In this study, a simple and rapid extraction method based on the application of
      polypyrrole-coated Fe3 O4 nanoparticles as a magnetic solid-phase extraction
      sorbent was successfully developed for the extraction and preconcentration of
      trace amounts of formaldehyde after derivatization with 2,4
      dinitrophenylhydrazine. The analyses were performed by high-performance liquid
      chromatography followed by UV detection. Several variables affecting the
      extraction efficiency of the formaldehyde, i.e., sample pH, amount of sorbent,
      salt concentration, extraction time and desorption conditions were investigated
      and optimized. The best working conditions were as follows: sample pH, 5; amount
      of sorbent, 40 mg; NaCl concentration, 20% w/v; sample volume, 20 mL; extraction
      time, 12 min; and 100 MUL of methanol for desorption of the formaldehyde within 3
      min. Under the optimal conditions, the performance of the proposed method was
      studied in terms of linear dynamic range (10-500 MUg/L), correlation coefficient
      (R(2) >= 0.998), precision (RSD% <= 5.5) and limit of detection (4 MUg/L).
      Finally, the developed method was successfully applied for extraction and
      determination of formaldehyde in tap, rain and tomato water samples, and
      satisfactory results were obtained. 

PMID- 26205229
TI  - Consuming a multi-ingredient thermogenic supplement for 28 days is apparently
      safe in healthy adults.
AB  - BACKGROUND: Thermogenic (TRM) supplements are often used by people seeking to
      decrease body weight. Many TRM supplements are formulated with multiple
      ingredients purported to increase energy expenditure and maximize fat loss.
      However, in the past some TRM ingredients have been deemed unsafe and removed
      from the market. Therefore, it is important to verify the safety of multi
      ingredient TRM supplements with chronic consumption. OBJECTIVE: To assess the
      safety of daily consumption of a multi-ingredient TRM supplement over a 28-day
      period in healthy adults. DESIGN: Twenty-three recreationally active adults (11M,
      12F; 27.1+/-5.4 years, 171.6+/-9.6 cm, 76.8+/-16.1 kg, 26+/-5 BMI) were randomly
      assigned either to consume a multi-ingredient TRM supplement (SUP; n=9) or remain
      unsupplemented (CRL; n=14) for 28 days. Participants maintained their habitual
      dietary and exercise routines for the duration of the study. Fasting blood
      samples, resting blood pressure, and heart rate were taken before and after the
      supplementation period. Samples were analyzed for complete blood counts,
      comprehensive metabolic, and lipid panels. RESULTS: Significant (p<0.05) group by
      time interactions were present for diastolic BP, creatinine, estimated glomerular
      filtration rate (eGFR), chloride, CO2, globulin, albumin:globulin (A/G), and high
      density lipoprotein (HDL). Dependent t-tests conducted on significant variables
      revealed significant (p<0.05) within-group differences in SUP for diastolic BP
      (+6.2+/-5.3 mmHG), creatinine (+0.09+/-0.05 mg/dL), eGFR (-11.2+/-5.8
      mL/min/1.73), globulin (-0.29+/-0.24 g/dL), A/G (+0.27+/-0.23), and HDL (-5.0+/
      5.5 mg/dL), and in CRL for CO2 (-1.9+/-1.5 mmol/L) between time points. Each
      variable remained within the accepted physiological range. CONCLUSION: Results of
      the present study support the clinical safety of a multi-ingredient TRM
      containing caffeine, green tea extract, and cayenne powder. Although there were
      statistically significant (p<0.05) intragroup differences in SUP from pre- to
      postsupplementation for diastolic BP, creatinine, eGFR, globulin, A/G, and HDL,
      all remained within accepted physiological ranges and were not clinically
      significant. In sum, it appears as though daily supplementation with a multi
      ingredient TRM is safe for consumption by healthy adults for a 28-day period.

PMID- 26205230
TI  - Mercury Contamination in an Indicator Fish Species from Andean Amazonian Rivers
      Affected by Petroleum Extraction.
AB  - Elevated mercury (Hg) concentrations in fish from Amazonia have been associated
      with gold-mining, hydroelectric dams and deforestation but few studies consider
      the role of petroleum extraction. Hg levels were determined in fish samples
      collected in three river basins in Ecuador and Peru with contrasting petroleum
      exploitation and land-use characteristics. The non-migratory, piscivorous
      species, Hoplias malabaricus, was used as a bioindicator. The rate of Hg increase
      with body weight for this species was significantly higher on the Corrientes
      River, near the site of a recent oil spill, than on the other two rivers. In the
      absence of substantial deforestation and other anthropogenic sources in the
      Corrientes River basin, this finding suggests that oil contamination in Andean
      Amazonia may have a significant impact on Hg levels in fish. 

PMID- 26205231
TI  - Transplanted Lichen Pseudovernia furfuracea as a Multi-Tracer Monitoring Tool
      Near a Solid Waste Incinerator in Italy: Assessment of Airborne Incinerator
      Related Pollutants.
AB  - The ability of a transplanted lichen, Pseudovernia (P.) furfuracea, to act as a
      multi-tracer biomonitoring tool for As, Cd, Ni, Pb, 12 PAHs, 17 polychlorinated
      dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and 27 polychlorinated
      biphenyls (PCBs) was evaluated at six areas of varying risk (high, medium,
      negligible) of pollutant fallout from a municipal waste incinerator in central
      Italy. Transplanted P. furfuracea proved to be an useful tool to biomonitor
      PCDDs/Fs and PCBs. Concentrations of As, heavy metals, PAHs, PCDDs/Fs resulted
      similar for all monitored stations. Small differences in total PCBs (4378 and
      4631 pg/g dw vs 3298, 4123, 3676 and 4022 pg/g dw) and dioxin-like PCBs (1235 and
      1265 pg/g dw vs 794, 1069, 1106 and 1188 pg/g dw) were observed. Air
      concentrations of monitored compounds appear to be more related to general air
      pollution than point emissions from the incinerator. 

PMID- 26205232
TI  - Brevibacterium frigoritolerans as a Novel Organism for the Bioremediation of
      Phorate.
AB  - Phorate, an organophosphorus insecticide, has been found effective for the
      control of various insect pests. However, it is an extremely hazardous
      insecticide and causes a potential threat to ecosystem. Bioremediation is a
      promising approach to degrade the pesticide from the soil. The screening of soil
      from sugarcane fields resulted in identification of Brevibacterium
      frigoritolerans, a microorganism with potential for phorate bioremediation was
      determined. B. frigoritolerans strain Imbl 2.1 resulted in the active
      metabolization of phorate by between 89.81% and 92.32% from soils amended with
      phorate at different levels (100, 200, 300 mg kg(-1) soil). But in case of
      control soil, 33.76%-40.92% degradation were observed. Among metabolites, sulfone
      was found as the main metabolite followed by sulfoxide. Total phorate residues
      were not found to follow the first order kinetics. This demonstrated that B.
      frigoritolerans has potential for bioremediation of phorate both in liquid
      cultures and agricultural soils.

PMID- 26205234
TI  - How to manage patients with hereditary haemorrhagic telangiectasia.
AB  - Hereditary haemorrhagic telangiectasia is a rare systemic autosomal dominantly
      inherited disorder of the fibrovascular tissue with a wide variety of clinical
      manifestations. Diagnosis is based on the clinical Curacao criteria or molecular
      genetic testing. Dilated vessels can develop into telangiectases or larger
      vascular malformations in various organs, calling for an interdisciplinary
      approach. Epistaxis and gastrointestinal bleeding can result from these vascular
      defects. Various conservative and interventional treatments have been described
      for these conditions. However, no optimal therapy exists. Treatment can become
      especially difficult due to progressive anaemia or when anticoagulant or anti
      thrombotic therapy becomes necessary. Screening for pulmonary arteriovenous
      malformations (PAVM) should be performed in all confirmed and suspected patients.
      Treatment by percutaneous transcatheter embolotherapy and antibiotic prophylaxis
      is normally effective for PAVM. Cerebral or hepatic vascular malformations and
      rare manifestations need to be evaluated on a case-by-case basis to determine the
      best course of action for treatment. 

PMID- 26205235
TI  - Photochemically-induced C-C bond formation between tertiary amines and nitrones.
AB  - Photoexcited nitrones serve as excellent electron acceptors as well as radical
      acceptors in the presence of tertiary amines to give beta-amino hydroxylamines
      via photochemically-induced direct sp(3) C-H functionalization of the tertiary
      amines. The combined use of an organophotosensitizer and photoirradiation was
      highly effective in accelerating addition reactions. Several nitrones and
      tertiary amines were successfully utilized to give beta-amino hydroxylamines in
      good yield. Highly regioselective generation of primary alpha-aminoalkyl radicals
      based on Lewis's stereoelectronic rule and diastereoselective addition reactions
      of primary alpha-aminoalkyl radicals with nitrones were successfully achieved.
      Furthermore, a highly diastereoselective reaction of an alpha-aminoalkyl radical
      with a chiral (E)-geometry-fixed alpha-alkoxycarbonylnitrone was performed. 

PMID- 26205233
TI  - Treatment of pelvic fractures through a less invasive ilioinguinal approach
      combined with a minimally invasive posterior approach.
AB  - BACKGROUND: Unstable pelvic fractures usually result from high-energy trauma.
      There are several treatment modalities available. The purpose of this study was
      to evaluate the clinical application of a new less invasive ilioinguinal approach
      combined with a minimally invasive posterior approach technique in patients with
      unstable pelvic fractures. We also address the feasibility, validity, and
      limitations of the technique. METHODS: Thirty-seven patients with unstable pelvic
      fractures were treated with our minimally invasive technique. The anterior pelvic
      ring fractures were treated with a less invasive ilioinguinal approach, and the
      sacral fractures were treated with a minimally invasive posterior approach. The
      clinical outcome was measured using the Majeed scoring system, and the quality of
      fracture reduction was evaluated. The patients were followed up for 13 to 60
      months (mean, 24 months). RESULTS: Anatomical or near to anatomical reduction was
      achieved in 26 (70.3 %) of the anterior pelvic ring fractures and a satisfactory
      result was obtained in another 11(29.7 %). For the posterior sacral fractures,
      excellent reduction was obtained in 33 (89.2 %) of the fractures, with a residual
      deformity in the other 4 patients. One superficial wound infection and two deep
      vein thromboses occurred, all of which resolved with conservative treatment. The
      clinical outcome at one year was "excellent" in 29 patients and "good" in 8
      patients (Majeed score). CONCLUSIONS: The satisfactory results showed that a
      reduction and fixation of unstable pelvic fractures is possible through a
      combination of a limited ilioinguinal approach and posterior pelvic ring
      fixation. We believe our method is a new and effective alternative in the
      management of pelvic fractures.

PMID- 26205236
TI  - The Affordable Care Act...or Is It?

PMID- 26205238
TI  - Charting the interactome of PDE3A in human cells using an IBMX based chemical
      proteomics approach.
AB  - In the cell the second messenger cyclic nucleotides cAMP and cGMP mediate a wide
      variety of external signals. Both signaling molecules are degraded by the
      superfamily of phosphodiesterases (PDEs) consisting of more than 50 different
      isoforms. Several of these PDEs are implicated in disease processes inspiring the
      quest for and synthesis of selective PDE inhibitors, that unfortunately have led
      to very mixed successes in clinical trials. This may be partially caused by their
      pharmacological action. Accumulating data suggests that small differences between
      different PDE isoforms may already result in specific tissue distributions,
      cellular localization and different involvement in higher order signal protein
      complexes. The role of PDEs in these higher order signal protein complexes has
      only been marginally addressed, as no screening methodology is available to
      address this in a more comprehensive way. Affinity based chemical proteomics is a
      relatively new tool to identify specific protein-protein interactions. Here, to
      study the interactome of PDEs, we synthesized a broad spectrum PDE-capturing
      resin based on the non-selective PDE inhibitor 3-isobutyl-1-methylxanthine
      (IBMX). Chemical proteomics characterization of this resin in HeLa cell lysates
      led to the capture of several different PDEs. Combining the IBMX-resin with in
      solution competition with the available more selective PDE inhibitors,
      cilostamide and papaverine, allowed us to selectively probe the interactome of
      PDE3A in HeLa cells. Besides known interactors such as the family of 14-3-3
      proteins, PDE3A was found to associate with a PP2A complex composed of a
      regulatory, scaffold and catalytic subunit. 

PMID- 26205239
TI  - Infantile Fistula-in-Ano: A Report of Two Patients and Review for Dermatologists.
AB  - Infantile fistula-in-ano is a well-known entity to pediatric surgeons but less
      recognized by dermatologists. Because these patients may initially present to a
      dermatologist or pediatric dermatologist, familiarity with the presentation is
      important. We present two infants with fistula-in-ano and review the literature
      on this condition. 

PMID- 26205240
TI  - Bent spine syndrome as an initial manifestation of late-onset multiple acyl-CoA
      dehydrogenase deficiency: a case report and literature review.
AB  - BACKGROUND: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is an
      autosomal recessive inherited disease of metabolic dysfunction clinically
      characterized by fluctuating proximal muscle weakness, excise intolerance, and
      dramatic riboflavin responsiveness. Dropped head syndrome can occasionally be
      observed in some severe patients with late-onset MADD; however, bent spine
      syndrome as an initial symptom had not been reported in patients with late-onset
      MADD. CASE PRESENTATION: A 46-year-old man lost the ability to hold his trunk
      upright, and had difficulty in raising his head, but he had no obvious symptoms
      of limb weakness. Meanwhile, he developed persistent numbness of limbs and lips
      around. Myopathological features and combined elevation of multiple
      acylcarnitines indicated that the axial myopathy might be caused by lipid storage
      myopathy. Cervical and lumbosacral MRI revealed a lot of abnormal signals
      diffusing along paravertebral muscles, while the abnormal signals almost
      disappeared after riboflavin treatment. Nerve conduction study indicated the
      patient suffering from predominantly sensory neuropathy and mildly motor
      neuropathy. Muscle pathology also demonstrated no typical neurogenic change,
      which was consistent with the electrophysiological findings. Causative mutations
      were found in the ETFDH gene. CONCLUSION: We report the first case of late-onset
      MADD with sensory neuropathy initially manifesting as bent spine syndrome and
      dropped head syndrome.

PMID- 26205241
TI  - A phase I/II trial of intraoperative breast radiotherapy in an Asian population:
      5-year results of local control and cosmetic outcome.
AB  - BACKGROUND: To date, there are no reports of intraoperative radiotherapy (IORT)
      use with long-term follow up as a method of accelerated partial breast
      irradiation (APBI) in Asian countries. We initiated a prospective phase I/II
      clinical trial of IORT in Japan in 2007, and herein, we report the 5-year follow
      up results. MATERIALS AND METHODS: The following inclusion criteria were used for
      enrollment in the trial: (1) tumor size < 2.5 cm, (2) desire for breast
      conserving surgery, (3) age >50 years, and (4) negative margins after resection.
      In February 2009, the eligibility criteria were changed to include only patients
      with sentinel lymph node-negative disease. In phase I, the radiotherapy dose was
      escalated from 19 Gy/fr to 21 Gy/fr, incremented by 1 Gy per step, with 3
      patients in each step. Doses were escalated after all patients in the preceding
      cohort had completed treatment and exhibited only grade 1 or 2 toxicities at a
      given dose level. The recommended phase II dose was set at 21 Gy at 90 % isodose.
      The primary endpoint was early toxicity. Secondary endpoints were long-term
      efficacy and late toxicity. In addition, Hypertrophic scarring was evaluated
      retrospectively as a cosmetic outcome by a radiation oncologist. RESULTS: Between
      December 2007 and March 2010, 32 women with breast cancer were enrolled in the
      trial. The median age was 65 years (51-80 years), and the median follow-up time
      was 6 years. No recurrence or metastasis was observed in any patient. Grade 2
      fibrosis was detected in 3 patients as an acute adverse event and in 2 patients
      as a late adverse event. Ten patients developed a hypertrophic scar 1 year after
      the IORT; the number of patients decreased to 7 in the 3 years of follow-up.
      CONCLUSION: The first group of female Asian patients tolerated the treatment with
      IORT in this Phase I/II study and remained recurrence-free for more than 5 years
      after treatment. However, 24 % of the patients developed hypertrophic scarring,
      an event that is being further examined in our ongoing multi-center Phase II
      trial of IORT for early breast cancer.

PMID- 26205242
TI  - Chemical Detoxification of Organomercurials.
AB  - Organomercurials including methylmercury are ubiquitous environmental pollutants
      and highly toxic to humans. Now it could be shown that N-methylimidazole based
      thiones/selones having an N-CH2CH2OH substituent are remarkably effective in
      detoxifying various organomercurials to produce less toxic HgE (E=S, Se)
      nanoparticles. Compounds lacking the N-CH2CH2OH substituent failed to produce HgE
      nanoparticles upon treatment with organomercurials, suggesting that this moiety
      plays a crucial role in the detoxification by facilitating the desulfurization
      and deselenization processes. This novel way of detoxifying organomercurials may
      lead to the discovery of new compounds to treat patients suffering from
      methylmercury poisoning.

PMID- 26205243
TI  - Candida glabrata: new tools and technologies-expanding the toolkit.
AB  - In recent years, there has been a noticeable rise in fungal infections related to
      non-albicans Candida species, including Candida glabrata which has both intrinsic
      resistance to and commonly acquired resistance to azole antifungals.
      Phylogenetically, C. glabrata is more closely related to the mostly non
      pathogenic model organism Saccharomyces cerevisiae than to other Candida species.
      Despite C. glabrata's designation as a pathogen by Wickham in 1957, relatively
      little is known about its mechanism of virulence. Over the past few years,
      technology to analyse the molecular basis of infection has developed rapidly, and
      here we briefly review the major advances in tools and technologies available to
      explore and investigate the virulence of C. glabrata that have occurred over the
      past decade. 

PMID- 26205244
TI  - Diversity and adaptive evolution of Saccharomyces wine yeast: a review.
AB  - Saccharomyces cerevisiae and related species, the main workhorses of wine
      fermentation, have been exposed to stressful conditions for millennia,
      potentially resulting in adaptive differentiation. As a result, wine yeasts have
      recently attracted considerable interest for studying the evolutionary effects of
      domestication. The widespread use of whole-genome sequencing during the last
      decade has provided new insights into the biodiversity, population structure,
      phylogeography and evolutionary history of wine yeasts. Comparisons between S.
      cerevisiae isolates from various origins have indicated that a variety of
      mechanisms, including heterozygosity, nucleotide and structural variations,
      introgressions, horizontal gene transfer and hybridization, contribute to the
      genetic and phenotypic diversity of S. cerevisiae. This review will summarize the
      current knowledge on the diversity and evolutionary history of wine yeasts,
      focusing on the domestication fingerprints identified in these strains. 

PMID- 26205245
TI  - Glucose repression in Saccharomyces cerevisiae.
AB  - Glucose is the primary source of energy for the budding yeast Saccharomyces
      cerevisiae. Although yeast cells can utilize a wide range of carbon sources,
      presence of glucose suppresses molecular activities involved in the use of
      alternate carbon sources as well as it represses respiration and gluconeogenesis.
      This dominant effect of glucose on yeast carbon metabolism is coordinated by
      several signaling and metabolic interactions that mainly regulate transcriptional
      activity but are also effective at post-transcriptional and post-translational
      levels. This review describes effects of glucose repression on yeast carbon
      metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and
      Snf1 signal transduction in establishment and relief of glucose repression. 

PMID- 26205246
TI  - KnowEnG: a knowledge engine for genomics.
AB  - We describe here the vision, motivations, and research plans of the National
      Institutes of Health Center for Excellence in Big Data Computing at the
      University of Illinois, Urbana-Champaign. The Center is organized around the
      construction of "Knowledge Engine for Genomics" (KnowEnG), an E-science framework
      for genomics where biomedical scientists will have access to powerful methods of
      data mining, network mining, and machine learning to extract knowledge out of
      genomics data. The scientist will come to KnowEnG with their own data sets in the
      form of spreadsheets and ask KnowEnG to analyze those data sets in the light of a
      massive knowledge base of community data sets called the "Knowledge Network" that
      will be at the heart of the system. The Center is undertaking discovery projects
      aimed at testing the utility of KnowEnG for transforming big data to knowledge.
      These projects span a broad range of biological enquiry, from pharmacogenomics
      (in collaboration with Mayo Clinic) to transcriptomics of human behavior. 

PMID- 26205247
TI  - Comparison of effectiveness of cefovecin, doxycycline, and amoxicillin for the
      treatment of experimentally induced early Lyme borreliosis in dogs.
AB  - BACKGROUND: While Koch's postulates have been fulfilled for Lyme disease; causing
      transient fever, anorexia and arthritis in young dogs; treatment of sero-positive
      dogs, especially asymptomatic animals, remains a topic of debate. To complicate
      this matter the currently recommended antibiotic treatments of Lyme Disease in
      dogs caused by Borrelia burgdorferi require daily oral administrations for 31
      days or longer, which makes non-compliance a concern. Additionally, there is no
      approved veterinary antimicrobial for the treatment of Lyme Disease in dogs in
      the USA and few recommended treatments have been robustly tested. In vitro
      testing of cefovecin, a novel extended-spectrum cephalosporin, demonstrated
      inhibition of spirochete growth. A small pilot study in dogs indicated that two
      cefovecin injections two weeks apart would be as efficacious against B.
      burgdorferi sensu stricto as the recommended treatments using doxycycline or
      amoxicillin daily for 31 days. This hypothesis was tested in 17-18 week old
      Beagle dogs, experimentally infected with B. burgdorferi sensu stricto, using
      wild caught ticks, 75 days prior to antimicrobial administration. RESULTS:
      Clinical observations for lameness were performed daily but were inconclusive as
      this characteristic sign of Lyme Disease rarely develops in the standard
      laboratory models of experimentally induced infection. However, each antibiotic
      tested was efficacious against B. burgdorferi as measured by a rapid elimination
      of spirochetes from the skin and reduced levels of circulating antibodies to B.
      burgdorferi. In addition, significantly less cefovecin treated animals had Lyme
      Disease associated histopathological changes compared to untreated dogs.
      CONCLUSIONS: Convenia was efficacious against B. burgdorferi sensu stricto
      infection in dogs as determined by serological testing, PCR and histopathology
      results. Convenia provides an additional and effective treatment option for Lyme
      Disease in dogs.

PMID- 26205249
TI  - Community Prevention Coalition Context and Capacity Assessment: Comparing the
      United States and Mexico.
AB  - Effective planning for community health partnerships requires understanding how
      initial readiness-that is, contextual factors and capacity-influences
      implementation of activities and programs. This study compares the context and
      capacity of drug and violence prevention coalitions in Mexico to those in the
      United States. Measures of coalition context include community problems,
      community leadership style, and sense of community. Measures of coalition
      capacity include the existence of collaborative partnerships and coalition
      champions. The assessment was completed by 195 members of 9 coalitions in Mexico
      and 139 members of 7 coalitions in the United States. Psychometric analyses
      indicate the measures have moderate to strong internal consistency, along with
      good convergent and discriminant validity in both settings. Results indicate that
      members of Mexican coalitions perceive substantially more serious community
      problems, especially with respect to education, law enforcement, and access to
      alcohol and drugs. Compared to respondents in the United States, Mexican
      respondents perceive sense of community to be weaker and that prevention efforts
      are not as valued by the population where the coalitions are located. The Mexican
      coalitions appear to be operating in a substantially more challenging environment
      for the prevention of violence and substance use. Their ability to manage these
      challenges will likely play a large role in determining whether they are
      successful in their prevention efforts. The context and capacity assessment is a
      valuable tool that coalitions can use in order to identify and address initial
      barriers to success. 

PMID- 26205251
TI  - Genetic and environmental risk factors in neurodevelopmental disorders.

PMID- 26205250
TI  - Selective Retinoic Acid Receptor gamma Agonists Promote Repair of Injured
      Skeletal Muscle in Mouse.
AB  - Retinoic acid signaling regulates several biological events, including
      myogenesis. We previously found that retinoic acid receptor gamma (RARgamma)
      agonist blocks heterotopic ossification, a pathological bone formation that
      mostly occurs in the skeletal muscle. Interestingly, RARgamma agonist also
      weakened deterioration of muscle architecture adjacent to the heterotopic
      ossification lesion, suggesting that RARgamma agonist may oppose skeletal muscle
      damage. To test this hypothesis, we generated a critical defect in the tibialis
      anterior muscle of 7-week-old mice with a cautery, treated them with RARgamma
      agonist or vehicle corn oil, and examined the effects of RARgamma agonist on
      muscle repair. The muscle defects were partially repaired with newly regenerating
      muscle cells, but also filled with adipose and fibrous scar tissue in both
      RARgamma-treated and control groups. The fibrous or adipose area was smaller in
      RARgamma agonist-treated mice than in the control. In addition, muscle repair was
      remarkably delayed in RARgamma-null mice in both critical defect and cardiotoxin
      injury models. Furthermore, we found a rapid increase in retinoid signaling in
      lacerated muscle, as monitored by retinoid signaling reporter mice. Together, our
      results indicate that endogenous RARgamma signaling is involved in muscle repair
      and that selective RARgamma agonists may be beneficial to promote repair in
      various types of muscle injuries. 

PMID- 26205252
TI  - The role of lymph nodes in predicting the prognosis of ampullary carcinoma after
      curative resection.
AB  - BACKGROUND: Lymph node involvement is one of the well-demonstrated prognostic
      factors in ampullary carcinoma. The aim of this study is to clarify the role of
      lymph nodes in predicting the survival outcome of ampullary carcinoma. METHODS: A
      cohort of consecutive curative pancreaticoduodenectomies for ampullary carcinoma
      from 1999 to 2014 was retrospectively analyzed. The effect of node-associated
      variables, including lymph node status, positive lymph node number, total
      harvested lymph node (THLN) number, and lymph node ratio (LNR) was examined using
      univariate and multivariate analyses for survival outcome prediction. RESULTS: In
      194 evaluable patients, univariate analysis demonstrated that stage, cell
      differentiation, perineural invasion, and nodal status were significant
      conventional prognostic factors. Concerning the node-associated variables,
      positive nodal status, positive lymph node number>=2, THLN number<14, and
      LNR>=0.15 were significantly associated with poorer survival outcomes, with a 5
      year survival rate of 20.3, 38.9, 25.4, and 18%, respectively. By multivariate
      analysis, nodal status and THLN number were two independent predictors of
      survival. The most favorable 5-year survival rate was 84.4% in patients with
      negative nodal involvement and THLN number>=14, compared with the poorest 5-year
      survival rate of 16.1% in those with positive nodal status and THLN number<14.
      CONCLUSIONS: Tumor biology reflected by lymph node status is the most important
      independent prognostic factor; nevertheless, surgical radicality based on THLN
      number also plays a significant role in the survival outcome for patients with
      ampullary carcinoma after curative pancreaticoduodenectomy.

PMID- 26205253
TI  - Rational Design of Cancer-Targeted Benzoselenadiazole by RGD Peptide
      Functionalization for Cancer Theranostics.
AB  - A cancer-targeted conjugate of the selenadiazole derivative BSeC (benzo[1,2,5]
      selenadiazole-5-carboxylic acid) with RGD peptide as targeting molecule and PEI
      (polyethylenimine) as a linker is rationally designed and synthesized in the
      present study. The results show that RGD-PEI-BSeC forms nanoparticles in aqueous
      solution with a core-shell nanostructure and high stability under physiological
      conditions. This rational design effectively enhances the selective cellular
      uptake and cellular retention of BSeC in human glioma cells, and increases its
      selectivity between cancer and normal cells. The nanoparticles enter the cells
      through receptor-mediated endocytosis via clathrin-mediated and nystatin
      dependent lipid raft-mediated pathways. Internalized nanoparticles trigger glioma
      cell apoptosis by activation of ROS-mediated p53 phosphorylation. Therefore, this
      study provides a strategy for the rational design of selenium-containing cancer
      targeted theranostics. 

PMID- 26205254
TI  - Deleterious effects of obesity upon the hormonal and molecular mechanisms
      controlling spermatogenesis and male fertility.
AB  - Worldwide obesity rates have nearly doubled since 1980 and currently over 10% of
      the population is obese. In 2008, over 1.4 billion adults aged 20 years and older
      had a body mass index or BMI above a healthy weight and of these, over 200
      million men and nearly 300 million women were obese. While obesity can have many
      ramifications upon adult life, one growing area of concern is that of
      reproductive capacity. Obesity affects male infertility by influencing the
      hypothalamic-pituitary-gonadal axis, thus causing detrimental effects upon
      spermatogenesis and subsequent fertility. In particular, evidence indicates that
      excess adipose tissue can alter the relative ratio of testosterone and oestrogen.
      Additional effects involve the homeostatic disruption of insulin, sex-hormone
      binding-globulin, leptin and inhibin B, leading to diminished testosterone
      production and impairment to spermatogenesis. Aberrant spermatogenesis arising
      from obesity is associated with downstream changes in key semen parameters,
      defective sperm capacitation and binding, and deleterious effects on sperm
      chromatin structure. More recent investigations into trans-generational
      epigenetic inheritance further suggest that molecular changes in sperm that arise
      from obesity-related impaired spermatogenesis, such as modified sperm RNA levels,
      DNA methylation, protamination and histone acetylation, can impact upon the
      development of offspring. Here, we summarise our current understanding of how
      obesity exerts influence over spermatogenesis and subsequent fertility status,
      and make recommendations for future investigative research. 

PMID- 26205256
TI  - Erratum to: Germline Mutations in NKX2-5, GATA4, and CRELD1 are Rare in a Mexican
      Sample of Down Syndrome Patients with Endocardial Cushion and Septal Heart
      Defects.

PMID- 26205255
TI  - Lack of additive role of ageing in nigrostriatal neurodegeneration triggered by
      alpha-synuclein overexpression.
AB  - INTRODUCTION: Parkinson's disease (PD) is a progressive neurodegenerative
      disorder characterized by the loss of dopaminergic neurons as well as the
      presence of proteinaceous inclusions named Lewy bodies. alpha-synuclein (alpha
      syn) is a major constituent of Lewy bodies, and the first disease-causing protein
      characterized in PD. Several alpha-syn-based animal models of PD have been
      developed to investigate the pathophysiology of PD, but none of them recapitulate
      the full picture of the disease. Ageing is the most compelling and major risk
      factor for developing PD but its impact on alpha-syn toxicity remains however
      unexplored. In this study, we developed and exploited a recombinant adeno
      associated viral (AAV) vector of serotype 9 overexpressing mutated alpha-syn to
      elucidate the influence of ageing on the dynamics of PD-related neurodegeneration
      associated with alpha-syn pathology in different mammalian species. RESULTS:
      Identical AAV pseudotype 2/9 vectors carrying the DNA for human mutant p.A53T
      alpha-syn were injected into the substantia nigra to induce neurodegeneration and
      synucleinopathy in mice, rats and monkeys. Rats were used first to validate the
      ability of this serotype to replicate alpha-syn pathology and second to
      investigate the relationship between the kinetics of alpha-syn-induced
      nigrostriatal degeneration and the progressive onset of motor dysfunctions,
      strikingly reminiscent of the impairments observed in PD patients. In mice,
      AAV2/9-halpha-syn injection into the substantia nigra was associated with
      accumulation of alpha-syn and phosphorylated halpha-syn, regardless of mouse
      strain. However, phenotypic mutants with either accelerated senescence or
      resistance to senescence did not display differential susceptibility to halpha
      syn overexpression. Of note, p-alpha-syn levels correlated with nigrostriatal
      degeneration in mice. In monkeys, halpha-syn-induced degeneration of the
      nigrostriatal pathway was not affected by the age of the animals. Unlike mice,
      monkeys did not exhibit correlations between levels of phosphorylated alpha-syn
      and neurodegeneration. CONCLUSIONS: In conclusion, AAV2/9-mediated halpha-syn
      induces robust nigrostriatal neurodegeneration in mice, rats and monkeys,
      allowing translational comparisons among species. Ageing, however, neither
      exacerbated nigrostriatal neurodegeneration nor alpha-syn pathology per se. Our
      unprecedented multi-species investigation thus favours the multiple-hit
      hypothesis for PD wherein ageing would merely be an aggravating, additive, factor
      superimposed upon an independent disease process.

PMID- 26205257
TI  - Multiple Approaches to Minimize Transfusions for Pediatric Patients in Open-Heart
      Surgery.
AB  - We have attempted to reduce blood use during the perioperative period to avoid
      complications associated with blood transfusions in pediatric patients undergoing
      open-heart surgery. We retrospectively reviewed clinical data of patients who
      underwent open-heart surgery (age < 15 years, body weight <= 30 kg) from January
      2012 to October 2013. Our strategy to reduce transfusion volume included: (1)
      shortening the length of cardiopulmonary bypass (CPB) circuit, and adding red
      blood cells (RBC) to CPB circuit priming solution when preoperative hematocrit
      was <=30%; (2) routine modified ultrafiltration in all patients; and (3)
      restricting RBC transfusions during postoperative period, given when hematocrit
      was <=25%. In total, 349 cases were enrolled. The median age of patients was 7
      months (1 day-168 months), and body weight was 7 kg (2.3-30 kg). We did not use
      blood products in 81 (23.2%) cases and did not add RBCs to CPB priming solution
      in 119 (34.1%) cases. Patients who did not require a transfusion showed a shorter
      intensive care unit (ICU) stays (0.97 +/- 0.5 days) than patients who required a
      transfusion (4.1 +/- 5.5 days, p = 0.003). Larger volume transfusion correlated
      with longer intubation durations, ICU and hospital stays, higher peak C-reactive
      protein levels, and an increased blood urea nitrogen/creatinine ratio. No
      significant problems were observed in patients with relatively lower hematocrit
      levels. Our strategy to reduce transfusion volume resulted in shorter ventilator
      support, ICU stay, hospitalization, reduced inflammatory reaction, and less
      kidney insult during the postoperative course in pediatric patients.

PMID- 26205258
TI  - Molecular cloning and characterization of an S-adenosylmethionine synthetase gene
      from Chorispora bungeana.
AB  - S-adenosylmethionine synthetase (SAMS) catalyzes the formation of S
      adenosylmethionine (SAM) which is a molecule essential for polyamines and
      ethylene biosynthesis, methylation modifications of protein, DNA and lipids. SAMS
      also plays an important role in abiotic stress response. Chorispora bungeana (C.
      bungeana) is an alpine subnival plant species which possesses strong tolerance to
      cold stress. Here, we cloned and characterized an S-adenosylmethionine synthetase
      gene, CbSAMS (C. bungeana S-adenosylmethionine synthetase), from C. bungeana,
      which encodes a protein of 393 amino acids containing a methionine binding motif
      GHPDK, an ATP binding motif GAGDQG and a phosphate binding motif GGGAFSGDK.
      Furthermore, an NES (nuclear export signal) peptide was identified through
      bioinformatics analysis. To explore the CbSAMS gene expression regulation, we
      isolated the promoter region of CbSAMS gene 1919bp upstream the ATG start codon,
      CbSAMSp, and analyzed its cis-acting elements by bioinformatics method. It was
      revealed that a transcription start site located at 320 bp upstream the ATG start
      codon and cis-acting elements related to light, ABA, auxin, ethylene, MeJA, low
      temperature and drought had been found in the CbSAMSp sequence. The gene
      expression pattern of CbSAMS was then analyzed by TR-qPCR and GUS assay method.
      The result showed that CbSAMS is expressed in all examined tissues including
      callus, roots, petioles, leaves, and flowers with a significant higher expression
      level in roots and flowers. Furthermore, the expression level of CbSAMS was
      induced by low temperature, ethylene and NaCl. Subcellular localization revealed
      that CbSAMS was located in the cytoplasm and nucleus but has a significant higher
      level in the nucleus. These results indicated a potential role of CbSAMS in
      abiotic stresses and plant growth in C. bungeana.

PMID- 26205259
TI  - Behavioural adaptations of argulid parasites (Crustacea: Branchiura) to major
      challenges in their life cycle.
AB  - Fish lice (Argulus spp.) are obligate ectoparasites, which contrary to most
      aquatic parasites, retain the ability to swim freely throughout the whole of
      their life. In fish farms, they can quickly increase in numbers and without
      effective control cause argulosis, which results in the reduced growth and
      survival of their fish hosts. The morphology of Argulus spp, including their
      sensory organs, is suitable for both parasitism and free-swimming. By spending a
      considerable amount of time away from their host, these parasites risk being
      excessively dispersed, which could endanger mating success. Here we present a
      review of recent studies on the behaviour of Argulus spp, especially the
      aggregative behaviour that mitigates the dilution of the parasite population.
      Aggregation of parasites, which is especially important during the period of
      reproduction, occurs on different scales and involves both the aggregation of the
      host and the aggregation of the parasites on the host. The main behavioural
      adaptations of Argulus spp, including searches for hosts and mates, host
      manipulation and host choice, are all focused on the fish. As these ectoparasites
      repeatedly change hosts and inflict skin damage, they can act as vectors for fish
      pathogens. The development of environmentally friendly measures for the control
      and prevention of argulosis needs to take into account the behaviour of the
      parasites. 

PMID- 26205260
TI  - Variation in chest pain emergency department admission rates and acute myocardial
      infarction and death within 30 days in the Medicare population.
AB  - OBJECTIVES: The objective was to assess the relationship between emergency
      department (ED) admission rates for Medicare beneficiaries with chest pain and
      outcomes, specifically 30-day rates of acute myocardial infarction (AMI) and
      mortality. METHODS: Using a 20% random sample of Medicare beneficiaries in 2009,
      158,295 beneficiaries with a primary diagnosis of chest pain at the conclusion of
      their ED visits were selected to assess outcomes based on the decision to
      hospitalize or discharge home. The proportions of these patients admitted to
      inpatient or observation status at 2,219 U.S. hospitals were calculated,
      adjusting for differences in patient and hospital characteristics. Both bivariate
      analysis and multivariable logistic regression were used to estimate the effect
      of the adjusted admission rates (designed to be a measure of care intensity) on
      patient outcomes. Other covariates in the multivariable model included patient
      demographics, medical conditions, and hospital utilization in the 30 days prior
      to the ED visits. Results from the bivariate and multivariable analyses were
      compared for consistency. RESULTS: The adjusted Medicare admission rate for ED
      patients with chest pain averaged 63% for the middle quintile of the patient
      sample and ranged from 38% to 81% in the lowest and highest quintiles. The
      multivariable model yielded estimates of 3.6 fewer cases of AMI (95% confidence
      interval [CI] = 1.5 to 5.1 cases) and 2.8 fewer deaths (95% CI = 0.6 to 4.1
      deaths) per 1,000 chest pain patients associated with an admission rate of 81%
      versus 38%. The estimates from the bivariate analysis were of similar magnitude.
      CONCLUSIONS: Considerable variation exists across U.S. hospitals in ED admission
      rates for Medicare patients with chest pain. Hospitals that approach admissions
      more conservatively (i.e., higher admission rates) in this population have lower
      rates of AMI and mortality.

PMID- 26205261
TI  - Posttranscriptional regulation of T-type Ca(2+) channel expression by interleukin
      6 in prostate cancer cells.
AB  - BACKGROUND: At early stages, the growth of prostate cancers is androgen
      dependent. At later stages, however, the growth of prostate cancers becomes
      androgen independent, which leads to an increase in mortality. The switch to an
      androgen-refractory state is associated with neuroendocrine differentiation (NED)
      of prostate cancer cells. Several factors including interleukin-6 (IL-6) and
      increased cAMP production promote NED of prostate cancer cells. In this work we
      investigated whether IL-6 evoked NED of LNCaP cells results in a significant
      change in T-type Ca(2+) channel expression in comparison to non-stimulated LNCaP
      cells. METHODS: T-type Ca(2+) channel subunit Cav3.2 expression was studied using
      PCR analysis, western blot and whole cell recordings. Tubulin IIIbeta expression
      and neurite-like morphology was assessed to investigate the role of T-type Ca(2+)
      channels in the differentiation of prostate cancer cells. RESULTS: Treatment of
      LNCaP cells with IL-6 for 4days evokes considerable morphological and biochemical
      changes consistent with NED. Transcripts of the T-type Ca(2+) channel subunit
      Cav3.2 but not Cav3.1 or Cav3.3 are detected in IL-6 stimulated cells. Real time
      PCR analysis of IL-6 stimulated cells indicates no significant change in Cav3.2
      mRNA expression in comparison to non-stimulated cells. LNCaP cells stimulated
      with IL-6 show a threefold increase in T-type Ca(2+) channel subunit Cav3.2
      protein expression, suggesting that channel expression is upregulated by a
      posttranscriptional mechanism. Electrophysiological recordings reveal that
      increased Cav3.2 protein expression following IL-6 stimulation of LNCaP cells
      does not result in increased expression of functional channels in the membrane.
      Functional expression of Cav3.2 channels in LNCaP cells is facilitated by co
      stimulation with IL-6 and the cAMP-stimulating agent, forskolin (FSK). Inhibition
      of T-type Ca(2+) channel activity in IL-6 stimulated LNCaP cells prevents the
      development of morphological characteristics consistent with NED. CONCLUSIONS:
      These results indicate that the functional expression of T-type Ca(2+) channels
      is regulated by the interplay of multiple factors in LNCaP cells.

PMID- 26205262
TI  - Immune response and gene mutations in protracted low-dose medical radiation
      exposed personnel.

PMID- 26205263
TI  - A Real-Time Infrared Ultra-Spectral Signature Classification Method via Spatial
      Pyramid Matching.
AB  - The state-of-the-art ultra-spectral sensor technology brings new hope for high
      precision applications due to its high spectral resolution. However, it also
      comes with new challenges, such as the high data dimension and noise problems. In
      this paper, we propose a real-time method for infrared ultra-spectral signature
      classification via spatial pyramid matching (SPM), which includes two aspects.
      First, we introduce an infrared ultra-spectral signature similarity measure
      method via SPM, which is the foundation of the matching-based classification
      method. Second, we propose the classification method with reference spectral
      libraries, which utilizes the SPM-based similarity for the real-time infrared
      ultra-spectral signature classification with robustness performance.
      Specifically, instead of matching with each spectrum in the spectral library, our
      method is based on feature matching, which includes a feature library-generating
      phase. We calculate the SPM-based similarity between the feature of the spectrum
      and that of each spectrum of the reference feature library, then take the class
      index of the corresponding spectrum having the maximum similarity as the final
      result. Experimental comparisons on two publicly-available datasets demonstrate
      that the proposed method effectively improves the real-time classification
      performance and robustness to noise. 

PMID- 26205264
TI  - A Multispectral Image Creating Method for a New Airborne Four-Camera System with
      Different Bandpass Filters.
AB  - This paper describes an airborne high resolution four-camera multispectral system
      which mainly consists of four identical monochrome cameras equipped with four
      interchangeable bandpass filters. For this multispectral system, an automatic
      multispectral data composing method was proposed. The homography registration
      model was chosen, and the scale-invariant feature transform (SIFT) and random
      sample consensus (RANSAC) were used to generate matching points. For the
      difficult registration problem between visible band images and near-infrared band
      images in cases lacking manmade objects, we presented an effective method based
      on the structural characteristics of the system. Experiments show that our method
      can acquire high quality multispectral images and the band-to-band alignment
      error of the composed multiple spectral images is less than 2.5 pixels. 

PMID- 26205265
TI  - A Geospatial Semantic Enrichment and Query Service for Geotagged Photographs.
AB  - With the increasing abundance of technologies and smart devices, equipped with a
      multitude of sensors for sensing the environment around them, information
      creation and consumption has now become effortless. This, in particular, is the
      case for photographs with vast amounts being created and shared every day. For
      example, at the time of this writing, Instagram users upload 70 million
      photographs a day. Nevertheless, it still remains a challenge to discover the
      "right" information for the appropriate purpose. This paper describes an approach
      to create semantic geospatial metadata for photographs, which can facilitate
      photograph search and discovery. To achieve this we have developed and
      implemented a semantic geospatial data model by which a photograph can be enrich
      with geospatial metadata extracted from several geospatial data sources based on
      the raw low-level geo-metadata from a smartphone photograph. We present the
      details of our method and implementation for searching and querying the semantic
      geospatial metadata repository to enable a user or third party system to find the
      information they are looking for. 

PMID- 26205266
TI  - Self-Balancing Position-Sensitive Detector (SBPSD).
AB  - Optical position-sensitive detectors (PSDs) are a non-contact method of tracking
      the location of a light spot. Silicon-based versions of such sensors are
      fabricated with standard CMOS technology, are inexpensive and provide a real
      time, analog signal output corresponding to the position of the light spot. An
      innovative type of optical position sensor was developed using two back-to-back
      connected photodiodes. These so called self-balancing position-sensitive
      detectors (SBPSDs) eliminate the need for external readout circuitry entirely.
      Fabricated prototype devices demonstrate linear, symmetric coordinate
      characteristics and a spatial resolution of 200 MUm for a 74 mm device. PSDs are
      commercially available only up to a length of 37 mm. Prototype devices were
      fabricated with various lengths up to 100 mm and can be scaled down to any size
      below that. 

PMID- 26205267
TI  - Low Power Resistive Oxygen Sensor Based on Sonochemical SrTi0.6Fe0.4O2.8
      (STFO40).
AB  - The current paper reports on a sonochemical synthesis method for manufacturing
      nanostructured (typical grain size of 50 nm) SrTi0.6Fe0.4O2.8 (Sono-STFO40)
      powder. This powder is characterized using X ray-diffraction (XRD), Mossbauer
      spectroscopy and Scanning Electron Microscopy (SEM), and results are compared
      with commercially available SrTi0.4Fe0.6O2.8 (STFO60) powder. In order to
      manufacture resistive oxygen sensors, both Sono-STFO40 and STFO60 are deposited,
      by dip-pen nanolithography (DPN) method, on an SOI (Silicon-on-Insulator) micro
      hotplate, employing a tungsten heater embedded within a dielectric membrane.
      Oxygen detection tests are performed in both dry (RH = 0%) and humid (RH = 60%)
      nitrogen atmosphere, varying oxygen concentrations between 1% and 16% (v/v), at a
      constant heater temperature of 650  degrees C. The oxygen sensor, based on the
      Sono-STFO40 sensing layer, shows good sensitivity, low power consumption (80 mW),
      and short response time (25 s). These performance are comparable to those
      exhibited by state-of-the-art O2 sensors based on STFO60, thus proving Sono
      STFO40 to be a material suitable for oxygen detection in harsh environments. 

PMID- 26205268
TI  - Evaluation of Fear Using Nonintrusive Measurement of Multimodal Sensors.
AB  - Most previous research into emotion recognition used either a single modality or
      multiple modalities of physiological signal. However, the former method allows
      for limited enhancement of accuracy, and the latter has the disadvantages that
      its performance can be affected by head or body movements. Further, the latter
      causes inconvenience to the user due to the sensors attached to the body. Among
      various emotions, the accurate evaluation of fear is crucial in many
      applications, such as criminal psychology, intelligent surveillance systems and
      the objective evaluation of horror movies. Therefore, we propose a new method for
      evaluating fear based on nonintrusive measurements obtained using multiple
      sensors. Experimental results based on the t-test, the effect size and the sum of
      all of the correlation values with other modalities showed that facial
      temperature and subjective evaluation are more reliable than electroencephalogram
      (EEG) and eye blinking rate for the evaluation of fear. 

PMID- 26205269
TI  - Collaborative WiFi Fingerprinting Using Sensor-Based Navigation on Smartphones.
AB  - This paper presents a method that trains the WiFi fingerprint database using
      sensor-based navigation solutions. Since micro-electromechanical systems (MEMS)
      sensors provide only a short-term accuracy but suffer from the accuracy
      degradation with time, we restrict the time length of available indoor navigation
      trajectories, and conduct post-processing to improve the sensor-based navigation
      solution. Different middle-term navigation trajectories that move in and out of
      an indoor area are combined to make up the database. Furthermore, we evaluate the
      effect of WiFi database shifts on WiFi fingerprinting using the database
      generated by the proposed method. Results show that the fingerprinting errors
      will not increase linearly according to database (DB) errors in smartphone-based
      WiFi fingerprinting applications. 

PMID- 26205270
TI  - Potentiometric NO2 Sensors Based on Thin Stabilized Zirconia Electrolytes and
      Asymmetric (La0.8Sr0.2)0.95MnO3 Electrodes.
AB  - Here we report on a new architecture for potentiometric NO2 sensors that features
      thin 8YSZ electrolytes sandwiched between two porous (La0.8Sr0.2)0.95MnO3 (LSM95)
      layers-one thick and the other thin-fabricated by the tape casting and co-firing
      techniques. Measurements of their sensing characteristics show that reducing the
      porosity of the supporting LSM95 reference electrodes can increase the response
      voltages. In the meanwhile, thin LSM95 layers perform better than Pt as the
      sensing electrode since the former can provide higher response voltages and
      better linear relationship between the sensitivities and the NO2 concentrations
      over 40-1000 ppm. The best linear coefficient can be as high as 0.99 with a
      sensitivity value of 52 mV/decade as obtained at 500  degrees C. Analysis of the
      sensing mechanism suggests that the gas phase reactions within the porous LSM95
      layers are critically important in determining the response voltages. 

PMID- 26205271
TI  - Wireless Sensor Network Optimization: Multi-Objective Paradigm.
AB  - Optimization problems relating to wireless sensor network planning, design,
      deployment and operation often give rise to multi-objective optimization
      formulations where multiple desirable objectives compete with each other and the
      decision maker has to select one of the tradeoff solutions. These multiple
      objectives may or may not conflict with each other. Keeping in view the nature of
      the application, the sensing scenario and input/output of the problem, the type
      of optimization problem changes. To address different nature of optimization
      problems relating to wireless sensor network design, deployment, operation,
      planing and placement, there exist a plethora of optimization solution types. We
      review and analyze different desirable objectives to show whether they conflict
      with each other, support each other or they are design dependent. We also present
      a generic multi-objective optimization problem relating to wireless sensor
      network which consists of input variables, required output, objectives and
      constraints. A list of constraints is also presented to give an overview of
      different constraints which are considered while formulating the optimization
      problems in wireless sensor networks. Keeping in view the multi facet coverage of
      this article relating to multi-objective optimization, this will open up new
      avenues of research in the area of multi-objective optimization relating to
      wireless sensor networks. 

PMID- 26205272
TI  - Cross-Layer Service Discovery Mechanism for OLSRv2 Mobile Ad Hoc Networks.
AB  - Service discovery plays an important role in mobile ad hoc networks (MANETs). The
      lack of central infrastructure, limited resources and high mobility make service
      discovery a challenging issue for this kind of network. This article proposes a
      new service discovery mechanism for discovering and advertising services
      integrated into the Optimized Link State Routing Protocol Version 2 (OLSRv2). In
      previous studies, we demonstrated the validity of a similar service discovery
      mechanism integrated into the previous version of OLSR (OLSRv1). In order to
      advertise services, we have added a new type-length-value structure (TLV) to the
      OLSRv2 protocol, called service discovery message (SDM), according to the
      Generalized MANET Packet/Message Format defined in Request For Comments (RFC)
      5444. Each node in the ad hoc network only advertises its own services. The
      advertisement frequency is a user-configurable parameter, so that it can be
      modified depending on the user requirements. Each node maintains two service
      tables, one to store information about its own services and another one to store
      information about the services it discovers in the network. We present simulation
      results, that compare our service discovery integrated into OLSRv2 with the one
      defined for OLSRv1 and with the integration of service discovery in Ad hoc On
      demand Distance Vector (AODV) protocol, in terms of service discovery ratio,
      service latency and network overhead. 

PMID- 26205273
TI  - Interferometric Reflectance Imaging Sensor (IRIS)--A Platform Technology for
      Multiplexed Diagnostics and Digital Detection.
AB  - Over the last decade, the growing need in disease diagnostics has stimulated
      rapid development of new technologies with unprecedented capabilities. Recent
      emerging infectious diseases and epidemics have revealed the shortcomings of
      existing diagnostics tools, and the necessity for further improvements. Optical
      biosensors can lay the foundations for future generation diagnostics by providing
      means to detect biomarkers in a highly sensitive, specific, quantitative and
      multiplexed fashion. Here, we review an optical sensing technology,
      Interferometric Reflectance Imaging Sensor (IRIS), and the relevant features of
      this multifunctional platform for quantitative, label-free and dynamic detection.
      We discuss two distinct modalities for IRIS: (i) low-magnification (ensemble
      biomolecular mass measurements) and (ii) high-magnification (digital detection of
      individual nanoparticles) along with their applications, including label-free
      detection of multiplexed protein chips, measurement of single nucleotide
      polymorphism, quantification of transcription factor DNA binding, and high
      sensitivity digital sensing and characterization of nanoparticles and viruses. 

PMID- 26205274
TI  - Discrimination of Rice with Different Pretreatment Methods by Using a
      Voltammetric Electronic Tongue.
AB  - In this study, an application of a voltammetric electronic tongue for
      discrimination and prediction of different varieties of rice was investigated.
      Different pretreatment methods were selected, which were subsequently used for
      the discrimination of different varieties of rice and prediction of unknown rice
      samples. To this aim, a voltammetric array of sensors based on metallic
      electrodes was used as the sensing part. The different samples were analyzed by
      cyclic voltammetry with two sample-pretreatment methods. Discriminant Factorial
      Analysis was used to visualize the different categories of rice samples; however,
      radial basis function (RBF) artificial neural network with leave-one-out cross
      validation method was employed for prediction modeling. The collected signal data
      were first compressed employing fast Fourier transform (FFT) and then significant
      features were extracted from the voltammetric signals. The experimental results
      indicated that the sample solutions obtained by the non-crushed pretreatment
      method could efficiently meet the effect of discrimination and recognition. The
      satisfactory prediction results of voltammetric electronic tongue based on RBF
      artificial neural network were obtained with less than five-fold dilution of the
      sample solution. The main objective of this study was to develop primary research
      on the application of an electronic tongue system for the discrimination and
      prediction of solid foods and provide an objective assessment tool for the food
      industry. 

PMID- 26205275
TI  - Integrated High Resolution Digital Color Light Sensor in 130 nm CMOS Technology.
AB  - This article presents a color light detection system integrated in 130 nm CMOS
      technology. The sensors and corresponding electronics detect light in a CIE XYZ
      color luminosity space using on-chip integrated sensors without any additional
      process steps, high-resolution analog-to-digital converter, and dedicated DSP
      algorithm. The sensor consists of a set of laterally arranged integrated
      photodiodes that are partly covered by metal, where color separation between the
      photodiodes is achieved by lateral carrier diffusion together with wavelength
      dependent absorption. A high resolution, hybrid, ?? ADC converts each photo
      diode's current into a 22-bit digital result, canceling the dark current of the
      photo diodes. The digital results are further processed by the DSP, which
      calculates normalized XYZ or RGB color and intensity parameters using linear
      transformations of the three photo diode responses by multiplication of the data
      with a transformation matrix, where the coefficients are extracted by training in
      combination with a pseudo-inverse operation and the least-mean square
      approximation. The sensor system detects the color light parameters with 22-bit
      accuracy, consumes less than 60 MUA on average at 10 readings per second, and
      occupies approx. 0.8 mm(2) of silicon area (including three photodiodes and the
      analog part of the ADC). The DSP is currently implemented on FPGA. 

PMID- 26205276
TI  - Real-Time PPP Based on the Coupling Estimation of Clock Bias and Orbit Error with
      Broadcast Ephemeris.
AB  - Satellite orbit error and clock bias are the keys to precise point positioning
      (PPP). The traditional PPP algorithm requires precise satellite products based on
      worldwide permanent reference stations. Such an algorithm requires considerable
      work and hardly achieves real-time performance. However, real-time positioning
      service will be the dominant mode in the future. IGS is providing such an
      operational service (RTS) and there are also commercial systems like Trimble RTX
      in operation. On the basis of the regional Continuous Operational Reference
      System (CORS), a real-time PPP algorithm is proposed to apply the coupling
      estimation of clock bias and orbit error. The projection of orbit error onto the
      satellite-receiver range has the same effects on positioning accuracy with clock
      bias. Therefore, in satellite clock estimation, part of the orbit error can be
      absorbed by the clock bias and the effects of residual orbit error on positioning
      accuracy can be weakened by the evenly distributed satellite geometry. In
      consideration of the simple structure of pseudorange equations and the high
      precision of carrier-phase equations, the clock bias estimation method coupled
      with orbit error is also improved. Rovers obtain PPP results by receiving
      broadcast ephemeris and real-time satellite clock bias coupled with orbit error.
      By applying the proposed algorithm, the precise orbit products provided by GNSS
      analysis centers are rendered no longer necessary. On the basis of previous
      theoretical analysis, a real-time PPP system was developed. Some experiments were
      then designed to verify this algorithm. Experimental results show that the newly
      proposed approach performs better than the traditional PPP based on International
      GNSS Service (IGS) real-time products. The positioning accuracies of the rovers
      inside and outside the network are improved by 38.8% and 36.1%, respectively. The
      PPP convergence speeds are improved by up to 61.4% and 65.9%. The new approach
      can change the traditional PPP mode because of its advantages of independence,
      high positioning precision, and real-time performance. It could be an alternative
      solution for regional positioning service before global PPP service comes into
      operation. 

PMID- 26205277
TI  - An Intervention to Enhance Obstetric and Newborn Care in India: A Cluster
      Randomized-Trial.
AB  - OBJECTIVES: This study assessed whether community mobilization and interventions
      to improve emergency obstetric and newborn care reduced perinatal mortality (PMR)
      and neonatal mortality rates (NMR) in Belgaum, India. METHODS: The cluster
      randomised controlled trial was conducted in Belgaum District, Karnataka State,
      India. Twenty geographic clusters were randomized to control or the intervention.
      The intervention engaged and mobilized community and health authorities to
      leverage support; strengthened community-based stabilization, referral, and
      transportation; and aimed to improve quality of care at facilities. RESULTS:
      17,754 Intervention births and 15,954 control births weighing >=1000 g,
      respectively, were enrolled and analysed. Comparing the baseline period to the
      last 6 months period, the NMR was lower in the intervention versus control
      clusters (OR 0.60, 95% CI 0.34-1.06, p = 0.076) as was the PMR (OR 0.74, 95% CI
      0.46-1.19, p = 0.20) although neither reached statistical significance. Rates of
      facility birth and caesarean section increased among both groups. There was
      limited influence on quality of care measures. CONCLUSIONS FOR PRACTICE: The
      intervention had large but not statistically significant effects on neonatal and
      perinatal mortality. Community mobilization and increased facility care may
      ultimately improve neonatal and perinatal survival, and are important in the
      context of the global transition towards institutional delivery.

PMID- 26205278
TI  - Acceptability of a Weight Management Intervention for Pregnant and Postpartum
      Women with BMI >=30 kg/m2: A Qualitative Evaluation of an Individualized, Home
      Based Service.
AB  - OBJECTIVES: There have been recent calls for more evidence regarding effective
      antenatal and postnatal interventions to address the serious health risks of
      maternal obesity and associated childhood obesity. The Maternal and Early Years
      Healthy Weight Service (MAEYS) is an innovative service, delivered by specialist
      healthy weight advisors, for obese women (BMI >=30 kg/m2) during pregnancy and up
      to 2 years after delivery. The service focuses on healthy gestational weight
      gain, postpartum weight loss and establishing healthy infant feeding and active
      play. MAEYS was adopted by six local health organizations in the U.K. as a 1 year
      pilot program. The aim of the present research was to assess the acceptability of
      this intervention among MAEYS participants. METHODS: Semi-structured interviews
      with 20 women, with data analyzed thematically. RESULTS: High levels of
      acceptability were reported. The convenience and comfort of home visits,
      personalized advice on diet and physical activity, supportive approach of the
      healthy weight advisor and regular weight monitoring were all cited as advantages
      of the service. Service users suggested that more frequent contact with advisors
      and practical support such as recipes would improve the service. CONCLUSIONS:
      MAEYS is a novel, community-based intervention delivered in the home which has
      demonstrated acceptability to its recipients. It therefore shows promise as an
      early intervention to reduce the risks of maternal obesity and subsequently
      reduce childhood obesity. An evaluation of the efficacy of MAEYS in preventing
      excess gestational weight gain and losing weight postpartum is now needed.

PMID- 26205279
TI  - Assessment of metal pollution in a former mining area in the NW Tunisia: spatial
      distribution and fraction of Cd, Pb and Zn in soil.
AB  - This study aims to evaluate the impact of the former mining Touiref district (NW
      Tunisia) on the spatial distribution of metal contamination. In order to
      characterize the metal content of the tailings and to assess how far the soils
      from the district could be impacted by metals, a sampling campaign was conducted.
      According to the spatial distribution concentration maps of potential toxic
      elements (PTE), the highest concentrations occur near the flotation tailings and
      in mining facilities and decrease abruptly with distance. These results confirm
      that wind is the main agent capable of dispersing metals in a W-E direction, with
      concentrations exceeding the standards of soil quality for Cd, Pb and Zn over
      several hundred metres away from the source, facilitated by the small-size
      fraction and low cohesion of tailings particles. Chemical fractionation showed
      that Pb and Cd were mainly associated with the acid-soluble fraction (carbonates)
      and Fe-(oxy) hydroxides, while Zn was mainly associated with Fe-(oxy) hydroxides
      but also with sulphides. Thus, the immobilization of metals in solution may be
      favoured by the alkaline conditions, promoted by carbonates dissolution. However,
      being carbonate important-bearing phases of Cd and Pb (but also for Zn), the
      dissolution facility of these minerals may enhance the release of metals,
      particularly far away from the mine where the physicochemical conditions can be
      different. Also, the metal uptake by plants in these alkaline conditions may be
      favoured, especially if secondary phases with high sorption ability are reduced
      at this site. A remediation plan to this area is needed, with particularly
      attention in the confinement of the tailings. 

PMID- 26205280
TI  - Equitable fund allocation, an economical approach for sustainable waste load
      allocation.
AB  - This research aims to study a novel approach for waste load allocation (WLA) to
      meet environmental, economical, and equity objectives, simultaneously. For this
      purpose, based on a simulation-optimization model developed for Haraz River in
      north of Iran, the waste loads are allocated according to discharge permit
      market. The non-dominated solutions are initially achieved through multiobjective
      particle swarm optimization (MOPSO). Here, the violation of environmental
      standards based on dissolved oxygen (DO) versus biochemical oxidation demand
      (BOD) removal costs is minimized to find economical total maximum daily loads
      (TMDLs). This can save 41% in total abatement costs in comparison with the
      conventional command and control policy. The BOD discharge permit market then
      increases the revenues to 45%. This framework ensures that the environmental
      limits are fulfilled but the inequity index is rather high (about 4.65). For
      instance, the discharge permit buyer may not be satisfied about the equity of
      WLA. Consequently, it is recommended that a third party or institution should be
      in charge of reallocating the funds. It means that the polluters which gain
      benefits by unfair discharges should pay taxes (or funds) to compensate the
      losses of other polluters. This intends to reduce the costs below the required
      values of the lowest inequity index condition. These compensations of equitable
      fund allocation (EFA) may help to reduce the dissatisfactions and develop WLA
      policies. It is concluded that EFA in integration with water quality trading
      (WQT) is a promising approach to meet the objectives.

PMID- 26205281
TI  - Spatial variability of organic layer thickness and carbon stocks in mature boreal
      forest stands--implications and suggestions for sampling designs.
AB  - Accurate field measurements from inventories across fine spatial scales are
      critical to improve sampling designs and to increase the precision of forest C
      cycling modeling. By studying soils undisturbed from active forest management,
      this paper gives a unique insight in the naturally occurring variability of
      organic layer C and provides valuable references against which subsequent and
      future sampling schemes can be evaluated. We found that the organic layer C
      stocks displayed great short-range variability with spatial autocorrelation
      distances ranging from 0.86 up to 2.85 m. When spatial autocorrelations are
      known, we show that a minimum of 20 inventory samples separated by ~5 m is needed
      to determine the organic layer C stock with a precision of +/-0.5 kg C m(-2). Our
      data also demonstrates a strong relationship between the organic layer C stock
      and horizon thickness (R (2) ranging from 0.58 to 0.82). This relationship
      suggests that relatively inexpensive measurements of horizon thickness can
      supplement soil C sampling, by reducing the number of soil samples collected, or
      to enhance the spatial resolution of organic layer C mapping. 

PMID- 26205282
TI  - Produced water irrigation changes the soil mesofauna community in a semiarid
      agroecosystem.
AB  - The scarcity of water in semiarid regions requires alternative sources for
      irrigation to improve agricultural production. Here, we aimed to evaluate the
      effects of produced water from oil exploration on the structure of soil mesofauna
      during the dry and rainy seasons in irrigated sunflower and castor bean fields in
      a Brazilian semiarid region. Three irrigation treatments were applied on plots
      cultivated with castor beans and sunflowers: produced water treated by filtration
      (filtrated) or treated by reverse osmosis (reverse osmosis) and groundwater. The
      mesofauna under the biofuel crops was collected and identified during the dry and
      rainy seasons. Although the abundance and richness of the total fauna did not
      differ between seasons in sunflower plots, the community was altered. In castor
      beans, the abundance, richness, and community of mesofauna observed in plots
      irrigated with produced water differed from the groundwater treatment. Irrigation
      with produced water promotes important changes in soil fauna community that
      justify their assessment for the maintenance and monitoring of agroecosystems. 

PMID- 26205283
TI  - Evaluation of heavy metal enrichment in Cochin estuary and its adjacent coast:
      multivariate statistical approach.
AB  - Temporal and spatial variations of heavy metals in the Cochin estuary and its
      adjacent coastline during three seasons were studied to investigate the impact of
      anthropogenic heavy metal pollution. Total organic carbon, sand, silt, clay and
      10 metals (Cd, Pb, Cr, Ni, Co, Cu, Zn, Mn, Mg and Fe) in the surface sediments
      were analysed. Multivariate statistical analyses like canonical correspondence
      analysis, principal component analysis and cluster analysis were used for source
      identification, integration of geochemical data and clustering of stations based
      on similarities. Enrichment factor, contamination factor and geoaccumulation
      index were used to assess the contamination level. From the study, it can be
      understood that estuary and coast are highly polluted especially with Cd, Zn, Pb
      and Ni. Anthropogenic influence of heavy metals was evidenced from both the
      principal component analysis and cluster analysis. Finer fractions (mud) of the
      sediment and the associated Fe oxy hydroxides might be playing major role in the
      transport of heavy metals in the system. Very high enrichment factor value
      observed suggested high anthropogenic pressure in the study area. All the
      stations in the northern part of the estuary showed very high enrichment factors
      indicating heavy load of Zn and Cd in this area which might have reached from the
      industrial area lying to the north side of the Cochin estuary. Pollution indices
      suggested that both the estuary and its adjacent coast were showing low
      contamination with respect to Cr, Mg, Mn and Fe; all other metals were causing
      low to extremely high levels of pollution in the study area. 

PMID- 26205284
TI  - The influence of wind farm development on the hydrochemistry and ecology of an
      upland stream.
AB  - Despite perceptions of pristine condition, upland environments are increasingly
      subject to a range of anthropogenic pressures including air pollution, climate
      change, land-use change and evolving land management strategies. Although they
      have received little attention to date, the large-scale development of upland
      wind farms also has the potential to disturb vegetation and soils, alter
      hydrology and water quality and, thus, impact freshwater ecosystems. This paper
      presents the findings of a 5-year study of the impacts of wind farm construction
      on the freshwater environment. Data on water quality, invertebrate and fish
      populations were collected for 2 years before construction and for the following
      3 years covering the construction period and the initial period of the farm's
      operation. In contrast to previous studies, the impacts of the wind farm
      development were assessed for a suite of potentially affected hydrochemical
      variables using a before-after-control-impact (BACI) analysis that allowed
      separation of construction effects from spatial and temporal variability in
      hydroclimatological conditions, thereby providing an improved, more robust
      evidence base. There was a small but significant negative effect of construction
      on pH, alkalinity (Alk) and acid neutralising capacity (ANC) in the upper part of
      the treatment catchment, which was where the wind farm was situated. The effects
      were more marked under higher flow conditions. It is hypothesised that this
      reflects changes in hydrological processes with increased near-surface runoff or
      organic acid mobilisation. There was no indication that either invertebrate
      community structure or fish densities were impacted by construction and the
      resulting effects on water quality. 

PMID- 26205286
TI  - Editorial overview: host-microbe interactions: viruses.

PMID- 26205285
TI  - Persistence behaviour of pretilachlor in puddled paddy fields under subtropical
      humid climate.
AB  - The paper delineates the field trials conducted to investigate the persistence
      behaviour and dissipation kinetics of pretilachlor in puddled paddy fields under
      subtropical humid climatic region. Matrix solid phase dispersion (MSPD) method
      was used for extraction of the pretilachlor from paddy grain and paddy soil
      samples collected from the experimental field. Pretilachlor residues were
      quantified using high-performance liquid chromatography (HPLC) with UV/Vis
      detector at 210 nm. The average recoveries of pretilachlor extracted from matrix
      ranged from 80.3 to 103.3% with standard deviation less than 10% and sensitivity
      of 0.01 MUg g(-1). The dissipation rate of pretilachlor in paddy field soil and
      paddy field water followed first-order kinetics with decrease in pretilachlor
      residues as a function of time. Faster dissipation of pretilachlor was observed
      in paddy field water than in paddy field soil with half life of 1.89-2.97 days
      and 7.52-9.58 days, respectively. At harvest, the residues of pretilachlor in the
      paddy soil and paddy crop samples were below the detection limit.

PMID- 26205287
TI  - Editorial overview: host-microbe interactions: fungi: heterogeneity in fungal
      cells, populations, and communities.

PMID- 26205288
TI  - Mechanisms of Improvement of Left Ventricular Function by Intracoronary Human
      Umbilical Cord-Derived Mesenchymal Stem Cell Infusion in Very Old Patients with
      Coronary Chronic Total Occlusion.
AB  - We have evaluated the safety and efficacy of intracoronary human umbilical cord
      derived mesenchymal stem cell (hUCMSC) treatment for very old patients with
      coronary chronic total occlusion. hUCMSCs could improve in the degree of ischemic
      myocardium, decrease in the infarct size and rise in left ventricular ejection
      fraction, but the involved mechanisms remain to be fully identified. We analyzed
      levels of circulating leukocytes, highsensitivity C-reactive protein (hs-CRP),
      interleukins (ILs), tumor necrosis factor-a (TNF-a), soluble tumor necrosis
      factor receptor-1 (sTNFR-1), soluble tumor necrosis factor receptor-2 (sTNFR-2),
      NT-proBNP, BNP, angiotensin 1-7 (Ang1-7), angiotensin II (Ang II) and aldosterone
      (Ald) in patients with hUCMSC therapy at baseline, 12, and 24 months. Levels of
      Ang1-7, IL-10, IL-37 and IL-17 were increased at 12 months and 24 months;
      leukocytes, hs- CRP, IL-1. 

PMID- 26205289
TI  - Long Noncoding RNA MALAT1: Insights into its Biogenesis and Implications in Human
      Disease.
AB  - Genome-wide studies have identified thousands of noncoding RNAs (ncRNAs) with no
      protein coding capacity. Among them, the long non-coding RNAs (lncRNAs), which
      are more than 200 nucleotides in length, recently are widely concerned for their
      crucial role in regulating biological processes and diseases. However, most
      lncRNAs are expressed at a very low level, and generally exhibit poor primary
      sequence conservation over evolution. Long non-coding RNA MALAT1 (metastasis
      associated lung adenocarcinoma transcript 1), also known as NEAT2 (nuclear
      enriched abundant transcript 2), is outstanding among the lncRNA family due to
      its evolutionarily high conservation and abundant expression throughout diferent
      mammalian species. Meanwhile, MALAT1 was one of the first lncRNAs that was
      demonstrated to be associated with a disease, namely non-small cell lung cancer
      (NSCLC). Subsequently, MALAT1 was identified in multiple types of physiological
      processes, such as alternative splicing, nuclear organization, epigenetic
      modulating of gene expression, and so on. Moreover, a growing number of evidences
      indicated that MALAT1 was also closely related to various pathological processes,
      ranging from diabetes complications to cancers.In this review, we will make a
      summary on current understanding of MALAT1 in different physiological or
      pathophysiological processes and discuss the potential therapeutic applications
      based on MALAT1 detection and inhibition. 

PMID- 26205290
TI  - Inhibition of glycine transporter 1: The yellow brick road to new schizophrenia
      therapy?
AB  - While pharmacological blockade of dopamine D2 receptor can effectively suppress
      the psychotic or positive symptoms of schizophrenia, there is no satisfactory
      medication for the negative and cognitive symptoms of schizophrenia in spite of
      the proliferation of second generation antipsychotic drugs. Excitements over a
      new class of third generation antipsychotics that might possibly fill this urgent
      medical need have been prompted by the recent development of glycine transporter
      1 (GlyT1) inhibitors. The impetus of this novel pharmacological strategy stems
      directly from the prevailing hypothesis that negative and cognitive symptoms are
      attributable to the hypofunction of glutamatergic signalling via the N-methyl-D
      aspartate (NMDA) receptor in the brain. Inhibition of GlyT1 reduces clearance of
      extra-cellular glycine near NMDA receptor-containing synapses, and thereby
      increases baseline occupancy of the glycine-B site at the NR1 subunit of the NMDA
      receptor, which is a prerequisite of channel activation upon stimulation by the
      excitatory neurotransmitter glutamate. Pharmacological inhibition of GlyT1 is
      expected to boost NMDA receptor function and therefore alleviate persistent
      negative and cognitive symptoms without excessive risk of excitotoxicity
      associated with direct NMDA receptor agonists. The recently completed phase III
      clinical trials of the Roche compound, bitopertin (a.k.a. RG1678 or RO-4917838)
      had initially raised hope that this new class of drugs might represent the first
      successful translation of the glutamate hypothesis of schizophrenia to the
      clinic. However, the outcomes of the multi-centre bitopertin clinical trials have
      been disappointing. The present review seeks to examine this promise through a
      critical survey of the latest clinical and preclinical findings on the
      therapeutic potential of GlyT1 inhibition or down-regulation. 

PMID- 26205291
TI  - Bitropic D3 Dopamine Receptor Selective Compounds as Potential Antipsychotics.
AB  - Neuropsychiatric disorders represent a substantial social and health care issue.
      The National Institutes of Health estimates that greater than 2 million adults
      suffer from neuropsychiatric disorders in the USA. These individuals experience
      symptoms that can include auditory hallucinations, delusions, unrealistic beliefs
      and cognitive dysfunction. Although antipsychotic medications are available,
      suboptimal therapeutic responses are observed for approximately one-third of
      patients. Therefore, there is still a need to explore new pharmacotherapeutic
      strategies for the treatment of neuropsychiatric disorders. Many of the
      medications that are used clinically to treat neuropsychiatric disorders have a
      pharmacological profile that includes being an antagonist at D2-like (D2, D3 and
      D4) dopamine receptor subtypes. However, dopamine receptor subtypes are involved
      in a variety of neuronal circuits that include movement coordination, cognition,
      emotion, affect, memory and the regulation of prolactin. Consequently, antagonism
      at D2-like receptors can also contribute to some of the adverse side effects
      associated with the long-term use of antipsychotics including the a) adverse
      extrapyramidal symptoms associated with the use of typical antipsychotics and b)
      metabolic side effects (weight gain, hyperglycemia, increased risk of diabetes
      mellitus, dyslipidemia and gynecomastia) associated with atypical antipsychotic
      use. Preclinical studies suggest that D3 versus D2 dopamine receptor selective
      compounds might represent an alternative strategy for the treatment of the
      symptoms of schizophrenia. In this review we discuss a) how bitropic
      Nphenylpiperazine D3 dopamine receptor selective compounds have been developed by
      modification of the primary (orthosteric) and secondary (allosteric or
      modulatory) pharmacophores to optimize D3 receptor affinity and D2/D3 binding
      selectivity ratios and b) the functional selectivity of these compounds. Examples
      of how these compounds might be modified to develop bivalent ligands capable of
      interacting with receptor dimers or oligomers are also provided. Preclinical
      studies using bitropic D3 dopamine receptor selective ligands are also discussed
      as strategy to pharmacologically dissect the role of the D2 and D3 dopamine
      receptor subtypes in animal models of neuropsychiatric, neurological and
      substance abuse disorders. This research has the potential to a) advance the
      understanding of the role of the D2 and D3 dopamine receptor subtypes in
      neuropsychiatric disorders and b) lead to new treatment strategies for
      neuropsychiatric disorders. 

PMID- 26205292
TI  - Suppressive effect of citalopram on plasma concentrations of thromboxane B2.
AB  - BACKGROUND: Citalopram, a selective serotonin reuptake inhibitor (SSRi), is
      widely used to treat major depression. Patients treated with SSRIs suffer more
      frequently from bleeding disorders caused by the antiplatelet effect of SSRIs.
      METHODS: To investigate the potential suppressive effect of citalopram treatment
      on plasma thromboxane B2 levels and its possible correlation with actual plasma
      concentration of citalopram. Plasma concentrations of thromboxane B2 and
      citalopram were examined in a cohort of 77 aspirin-treated geriatric patients
      before and in the third week of citalopram therapy. RESULTS: Citalopram therapy
      led to a significant decrease of plasma concentrations of thromboxane B2 compared
      to its levels before initiation of the therapy. Furthermore, we have shown
      negative correlation in thromboxane B2 levels and actual plasma concentration of
      citalopram. Actual plasma concentrations of citalopram were significantly higher
      compared to younger adult patients treated with similar dose. CONCLUSIONS: In
      this study we have shown that even short-term citalopram therapy led to a
      suppression of thromboxane B2 production in aspirin-treated patients. This
      suppressive effect correlates with actual plasma concentration of citalopram.

PMID- 26205293
TI  - The soluble transcobalamin receptor (sCD320) is present in cerebrospinal fluid
      and correlates to dementia-related biomarkers tau proteins and amyloid-beta.
AB  - BACKGROUND: Cellular uptake of vitamin B12 (B12) demands binding of the vitamin
      to transcobalamin (TC) and recognition of TC-B12 (holoTC) by the receptor CD320.
      Recently, we identified a soluble form of CD320 (sCD320) in human plasma. Here we
      present data on the occurrence of this soluble receptor in cerebrospinal fluid
      (CSF) and show its correlations to dementia-related biomarkers tau proteins and
      amyloid-beta. METHODS: We collected 223 cerebrospinal fluid samples and
      corresponding plasma samples (n = 46). We measured CSF and plasma sCD320, holoTC
      and total TC employing in-house ELISA methods and CSF phospho-tau (181P) (p-tau),
      total tau (t-tau) and amyloid-beta 1-42 (Abeta) (n = 177) employing commercial
      ELISA kits (Innogenetics Company). Size exclusion chromatography was performed on
      a Superdex 200 column. RESULTS: The median sCD320 concentration in CSF (14
      pmol/L) is around five times lower than in plasma (72 pmol/L). No correlation was
      observed between plasma and CSF sCD320 levels (n = 46), while the behavior upon
      size exclusion chromatography was the same. In CSF, sCD320 correlates to holoTC
      and total TC (Spearman's correlation (Rs) = 0.325, 0.232 (n = 218, 217)
      respectively, p < 0.01). Interestingly, sCD320 correlates to p-tau and t-tau (Rs
      = 0.599, 0.569 (n = 173, 176) respectively, p < 0.001) and to Abeta (Rs = 0.265,
      p < 0.001 (n = 177)). CONCLUSION: We document for the first time the occurrence
      of sCD320 in human CSF. We report that the concentration of sCD320 correlates to
      the dementia-related biomarkers p-tau, t-tau and Abeta.

PMID- 26205294
TI  - Shedded cell membrane proteins in plasma: Pure waste, or informative biomarkers
      of pathophysiological processes?

PMID- 26205295
TI  - Estrogen regulation of the transient outward K(+) current involves estrogen
      receptor alpha in mouse heart.
AB  - BACKGROUND AND OBJECTIVE: We have previously shown that androgens upregulate
      cardiac K(+) channels and shorten repolarization. However, the effects that
      estrogens (E2) and estrogen receptors (ER) might have on the various repolarizing
      K(+) currents and underlying ion channels remain incompletely understood.
      Accordingly, our objective was to verify whether and how E2 and its ERs subtypes
      influence these K(+) currents. METHODS AND RESULTS: In order to examine the
      influence of E2 and ERs on K(+) currents we drastically lowered the E2 level
      through ovariectomy (OVX; 74% reduction vs CTL) and in parallel, we used female
      mice lacking either ERalpha (ERalphaKO) or ERbeta (ERbetaKO). In OVX mice,
      results showed a specific increase of 35% in the density of the Ca(2+)
      independent transient outward K(+) current (Ito) compared to CTL. Western blots
      showed increase in Kv4.2 and Kv4.3 sarcolemmal protein expression while qPCR
      revealed higher mRNA expression of only Kv4.3 in OVX mice. This upregulation of
      Ito was correlated with a shorter ventricular action potential duration and QTc
      interval. In ERalphaKO but not ERbetaKO mice, the mRNA of Kv4.3 was selectively
      increased. Furthermore, when ventricular myocytes obtained from ERalphaKO and
      ERbetaKO were cultured in the presence of E2, results showed that E2 reduced Ito
      density only in ERbetaKO myocytes confirming the repressive role of E2-ERalpha in
      regulating Ito. CONCLUSION: Altogether, these results suggest that E2 negatively
      regulates the density of Ito through ERalpha, this highlights a potential role
      for this female hormone and its alpha-subtype receptor in modulating cardiac
      electrical activity.

PMID- 26205296
TI  - RNA (Epi)genetics in cardiovascular diseases.
AB  - Next-generation sequencing has greatly improved our knowledge of the mammalian
      transcriptome, identifying thousands of non-coding RNAs (ncRNAs), which are RNAs
      that rather than translate for proteins, have regulatory functions. Perhaps
      unsurprisingly, dysregulation of individual ncRNAs has been associated with the
      development of pathologies, including of the cardiovascular system. The best
      characterized group of ncRNAs is represented by the short, highly conserved RNAs
      named microRNAs (miRNAs). This ncRNA species, which principally exerts an
      inhibitory action on gene expression, has been implicated in many cardiovascular
      diseases. Unfortunately, the complexity of action of other types of ncRNA, such
      as long ncRNAs, has somewhat hampered the study of their role in cardiovascular
      pathologies. A detailed characterization of the mechanism of action of these
      different ncRNA species would be conducive to a better understanding of the
      cellular processes underlying cardiovascular disease and may lead to the
      development of innovative therapeutic strategies. Here, we give an overview of
      the current knowledge on the function of ncRNAs and their roles in cardiovascular
      disease development, concentrating mainly on microRNAs and long ncRNAs. 

PMID- 26205297
TI  - New Approaches for Modeling Radiopharmaceutical Pharmacokinetics Using Continuous
      Distributions of Rates.
AB  - Radiopharmaceutical pharmacokinetics are usually approximated by sums of discrete
      first-order rates, using 3 or more parameters. We hypothesized that
      pharmacokinetic processes can be modeled even better by continuous probability
      distributions (CPD) of rates, using only 1-2 parameters. METHODS: To test this
      hypothesis, we used biodistribution data for 188Re-labeled melanin-specific
      antibody in blood, kidneys, liver, bone marrow, and lungs of melanoma xenograft
      bearing mice. We used 3 discrete-rate models (monoexponential, monoexponential
      with constant, and biexponential) and 4 CPD models (stretched-exponential,
      modified stretched-exponential, simplified versions of stretched-exponential, and
      modified stretched-exponential). They were compared by sample-size-corrected
      Akaike information criterion. Total time integrals of radioactivity were computed
      for each model and averaged across all models. RESULTS: The ratio of weights of
      evidence for CPD versus discrete-rate models was high for blood (12.2) and lungs
      (2.7), almost unity (0.99) for bone marrow, and slightly lower for kidneys (0.81)
      and liver (0.73). In all organs or tissues except lungs, model-averaged time
      integrals were 12.7%-54.0% higher than biexponential model estimates. CONCLUSION:
      Simple CPD models often outperform more complex discrete-rate models on
      pharmacokinetic data. Radioactivity time integrals are more robustly estimated by
      multimodel inference than using any single model.

PMID- 26205298
TI  - Monte Carlo Evaluation of Auger Electron-Emitting Theranostic Radionuclides.
AB  - Several radionuclides used in medical imaging emit Auger electrons, which,
      depending on the targeting strategy, either may be exploited for therapeutic
      purposes or may contribute to an unintentional mean absorbed dose burden. In this
      study, the virtues of 12 Auger electron-emitting radionuclides were evaluated in
      terms of cellular S values in concentric and eccentric cell-nucleus arrangements
      and by comparing their dose-point kernels. METHODS: The Monte Carlo code PENELOPE
      was used to transport the full particulate spectrum of (67)Ga, (80m)Br, (89)Zr,
      (90)Nb, (99m)Tc, (111)In, (117m)Sn, (119)Sb, (123)I, (125)I, (195m)Pt, and
      (201)Tl by means of event-by-event simulations. Cellular S values were calculated
      for varying cell and nucleus radii, and the effects of cell eccentricity on S
      values were evaluated. Dose-point kernels were determined up to 30 MUm. Energy
      deposition at DNA scales was also compared with an alpha emitter, (223)Ra.
      RESULTS: PENELOPE-determined S values were generally within 10% of MIRD values
      when the source and target regions strongly overlapped, that is, S(nucleus<
      nucleus) configurations, but greater differences were noted for S(nucleus<
      cytoplasm) and S(nucleus<-cell surface) configurations. Cell eccentricity had the
      greatest effect when the nucleus was small, compared with the cell size, and when
      the radiation sources were on the cell surface. Dose-point kernels taken together
      with the energy spectra of the radionuclides can account for some of the
      differences in energy deposition patterns between the radionuclides. The energy
      deposition of most Auger electron emitters at DNA scales of 2 nm or less exceeded
      that of a monoenergetic 5.77-MeV alpha particle, but not for (223)Ra. CONCLUSION:
      A single-cell dosimetric approach is required to evaluate the efficacy of
      individual radionuclides for theranostic purposes, taking cell geometry into
      account, with internalizing and noninternalizing targeting strategies.

PMID- 26205299
TI  - Dose Optimization of the Administered Activity in Pediatric Bone Scintigraphy:
      Validation of the North American Consensus Guidelines.
AB  - The 2010 North American Consensus Guidelines (NACG) for pediatric administered
      doses and the European Association of Nuclear Medicine (EANM) Dosage Card
      guidelines recommend lower activities than those administered at our institution.
      We compared the quality of the lower-activity images with the higher-activity
      images to determine whether the reduction in counts affects overall image
      quality. METHODS: Twenty patients presenting to our pediatric radiology
      department for bone scintigraphy were evaluated. Their mean weight was 20 kg. The
      patients were referred for oncologic (n = 10), infectious/inflammatory (n = 5),
      and pain (n = 5) evaluation. Dynamic anterior and posterior images were acquired
      for 5 min for each patient. Data were subsampled to represent different
      administered activities corresponding to the activities recommended by the NACG
      and the EANM Dosage Card. Images were evaluated twice, first for diagnostic
      quality and then for acceptability for daily clinical use. RESULTS: There was no
      statistically significant difference in the diagnostic quality of the images from
      any of the 3 protocols. Pathologic uptake was correctly identified independent of
      the administered activity, although there was a single false-positive result for
      an EANM image. When images were subjectively evaluated as acceptable for daily
      clinical use, there was a slight preference for the higher-activity images over
      the NACG (P = 0.04). CONCLUSION: The recommended administered activities of the
      NACG produce images of diagnostic quality while reducing patient radiation
      exposure.

PMID- 26205300
TI  - Radioisotopic Purity of Sodium Pertechnetate 99mTc Produced with a Medium-Energy
      Cyclotron: Implications for Internal Radiation Dose, Image Quality, and Release
      Specifications.
AB  - Cyclotron production of 99mTc is a promising route to supply 99mTc
      radiopharmaceuticals. Higher 99mTc yields can be obtained with medium-energy
      cyclotrons in comparison to those dedicated to PET isotope production. To take
      advantage of this capability, evaluation of the radioisotopic purity of 99mTc
      produced at medium energy (20-24 MeV) and its impact on image quality and
      dosimetry was required. METHODS: Thick 100Mo (99.03% and 99.815%) targets were
      irradiated with incident energies of 20, 22, and 24 MeV for 2 or 6 h. The targets
      were processed to recover an effective thickness corresponding to approximately 5
      MeV energy loss, and the resulting sodium pertechnetate 99mTc was assayed for
      chemical, radiochemical, and radionuclidic purity. Radioisotopic content in final
      formulation was quantified using gamma-ray spectrometry. The internal radiation
      dose for 99mTc-pertechnetate was calculated on the basis of experimentally
      measured values and biokinetic data in humans. Planar and SPECT imaging were
      performed using thin capillary and water-filled Jaszczak phantoms. RESULTS:
      Extracted sodium pertechnetate 99mTc met all provisional quality standards. The
      formulated solution for injection had a pH of 5.0-5.5, contained greater than 98%
      of radioactivity in the form of pertechnetate ion, and was stable for at least 24
      h after formulation. Radioisotopic purity of 99mTc produced with 99.03% enriched
      100Mo was greater than 99.0% decay corrected to the end of bombardment (EOB). The
      radioisotopic purity of 99mTc produced with 99.815% enriched 100Mo was 99.98% or
      greater (decay corrected to the EOB). The estimated dose increase relative to
      99mTc without any radionuclidic impurities was below 10% for sodium pertechnetate
      99mTc produced from 99.03% 100Mo if injected up to 6 h after the EOB. For 99.815%
      100Mo, the increase in effective dose was less than 2% at 6 h after the EOB and
      less than 4% at 15 h after the EOB when the target was irradiated at an incident
      energy of 24 MeV. Image spatial resolution and contrast with cyclotron-produced
      99mTc were equivalent to those obtained with 99mTc eluted from a conventional
      generator. CONCLUSION: Clinical-grade sodium pertechnetate 99mTc was produced
      with a cyclotron at medium energies. Quality control procedures and release
      specifications were drafted as part of a clinical trial application that received
      approval from Health Canada. The results of this work are intended to contribute
      to establishing a regulatory framework for using cyclotron-produced 99mTc in
      routine clinical practice.

PMID- 26205301
TI  - beta-Radioluminescence Imaging: A Comparative Evaluation with Cerenkov
      Luminescence Imaging.
AB  - Cerenkov luminescence imaging (CLI) can provide high-resolution images of (18)F
      FDG-avid tumors but requires prolonged acquisition times because of low photon
      sensitivity. In this study, we proposed a new modality, termed beta
      radioluminescence imaging (beta-RLI), which incorporates a scintillator with a
      gamma-rejection strategy for imaging beta particles. We performed a comparative
      evaluation of beta-RLI with CLI in both in vitro and in vivo systems. METHODS:
      Using in vitro phantoms, we characterized the photon sensitivity and resolution
      of CLI and beta-RLI. We also conducted a series of in vivo experiments with
      xenograft mouse models using both amelanotic (A375, UMSCC1-Luc) and melanotic
      (B16F10-Luc) cell lines. The B16F10 and UMSCC1 cell lines were transfected with
      the luciferase gene (Luc). CLI was acquired over 300 s, and beta-RLI was acquired
      using two 10-s acquisitions. We correlated (18)F -: FDG activities, as assessed
      by PET, with tumor radiances for both beta-RLI and CLI. We also compared tumor
      signal-to-background ratios (SBRs) between these modalities for amelanotic and
      melanotic tumors. RESULTS: For in vitro experiments, the photon sensitivity for
      beta-RLI was 560-fold greater than that for CLI. However, the spatial resolution
      for beta-RLI (4.4 mm) was inferior to that of CLI (1.0 mm). For in vivo
      experiments, correlations between (18)F-FDG activity and tumor radiance were 0.52
      (P < 0.01) for beta-RLI, 0.81 (P = 0.01) for amelanotic lesions with CLI, and 
      0.08 (negative contrast; P = 0.80) for melanotic lesions with CLI. Nine of 13
      melanotic lesions had an SBR less than 1 for CLI, despite an SBR greater than 1
      among all lesions for beta-RLI. CONCLUSION: beta-RLI can produce functional
      images of both amelanotic and melanotic tumors in a shorter time frame than CLI.
      Further engineering developments are needed to realize the full clinical
      potential of this modality.

PMID- 26205302
TI  - Trimeric Radiofluorinated Sulfonamide Derivatives to Achieve In Vivo Selectivity
      for Carbonic Anhydrase IX-Targeted PET Imaging.
AB  - Carbonic anhydrase IX (CA-IX), a transmembrane enzyme, mediates cell survival
      under hypoxic conditions and is overexpressed in solid malignancies. In this
      study, we synthesized four (18)F sulfonamide derivatives and evaluated their
      potential for imaging CA-IX expression with PET. METHODS: Azide derivatives of 2
      carbonic anhydrase inhibitors, 4-(2-aminoethyl)benzenesulfonamide (AEBS) and 4
      aminobenzensulfonamide (ABS), were coupled to radiosynthons with either 1 or 3
      alkynes and a pendent ammoniomethyltrifluoroborate (AmBF3) to generate monovalent
      or trivalent enzyme inhibitors. Binding affinity to CA-IX and other CA isoforms
      was determined via a stopped-flow, CA-catalyzed CO2 hydration assay. Tracers were
      radiolabeled via (18)F-(19)F isotope exchange reactions. Imaging/biodistribution
      studies were performed using HT-29 tumor-bearing immunocompromised mice. RESULTS:
      Monomeric AmBF3-AEBS and AmBF3-ABS were obtained in 41% and 40% yields, whereas
      trimeric AmBF3-(AEBS)3 and AmBF3-(ABS)3 were obtained in 47% and 55% yields,
      respectively. Derivatives bound CA-I, -II, -IX, and -XII with good affinity (0.49
      100.3 nM). (18)F-labeled sulfonamides were obtained in 16.3%-36.8% non-decay
      corrected radiochemical yields, with 40-207 GBq/MUmol specific activity and
      greater than 95% radiochemical purity. Biodistribution/imaging studies showed
      that the tracers were excreted through both renal and hepatobiliary pathways. At
      1 h after injection, HT-29 tumor xenografts were clearly visualized in PET images
      with modest contrast for all 4 tracers. Tumor uptake was 2-fold higher for
      monovalent tracers (~0.60 percentage injected dose per gram [%ID/g]) than for
      trivalent tracers (~0.30 %ID/g); however, tumor-to-background ratios were
      significantly better for (18)F-AmBF3-(ABS)3. Preblocking with acetazolamide
      reduced more than 80% uptake of (18)F-AmBF3-(ABS)3 in HT-29 tumors. CONCLUSION:
      Our data suggest that trimerization of an otherwise nonspecific CA inhibitor
      greatly enhances the selectivity for CA-IX in vivo and represents a promising
      strategy for creating multivalent enzyme inhibitors for selectively imaging
      extracellular enzyme activity by PET.

PMID- 26205303
TI  - High Concordance Between Mental Stress-Induced and Adenosine-Induced Myocardial
      Ischemia Assessed Using SPECT in Heart Failure Patients: Hemodynamic and
      Biomarker Correlates.
AB  - Mental stress can trigger myocardial ischemia, but the prevalence of mental
      stress-induced ischemia in congestive heart failure (CHF) patients is unknown. We
      characterized mental stress-induced and adenosine-induced changes in myocardial
      perfusion and neurohormonal activation in CHF patients with reduced left
      ventricular function using SPECT to precisely quantify segment-level myocardial
      perfusion. METHODS: Thirty-four coronary artery disease patients (mean age+/-SD,
      62+/-10 y) with CHF longer than 3 mo and ejection fraction less than 40%
      underwent both adenosine and mental stress myocardial perfusion SPECT on
      consecutive days. Mental stress consisted of anger recall (anger-provoking
      speech) followed by subtraction of serial sevens. The presence and extent of
      myocardial ischemia was quantified using the conventional 17-segment model.
      RESULTS: Sixty-eight percent of patients had 1 ischemic segment or more during
      mental stress and 81% during adenosine. On segment-by-segment analysis, perfusion
      with mental stress and adenosine were highly correlated. No significant
      differences were found between any 2 time points for B-type natriuretic peptide,
      tumor necrosis factor-alpha, IL-1b, troponin, vascular endothelin growth factor,
      IL-17a, matrix metallopeptidase-9, or C-reactive protein. However, endothelin-1
      and IL-6 increased, and IL-10 decreased, between the stressor and 30 min after
      stress. Left-ventricular end diastolic dimension was 179+/-65 mL at rest and
      increased to 217+/-71 after mental stress and 229+/-86 after adenosine (P<0.01
      for both). Resting end systolic volume was 129+/-60 mL at rest and increased to
      158+/-66 after mental stress (P<0.05) and 171+/-87 after adenosine (P<0.07), with
      no significant differences between adenosine and mental stress. Ejection fraction
      was 30+/-12 at baseline, 29+/-11 with mental stress, and 28+/-10 with adenosine
      (P=not significant). CONCLUSION: There was high concordance between ischemic
      perfusion defects induced by adenosine and mental stress, suggesting that mental
      stress is equivalent to pharmacologic stress in eliciting clinically significant
      myocardial perfusion defects in CHF patients. Cardiac dilatation suggests
      clinically important changes with both conditions. Psychosocial stressors during
      daily life may contribute to the ischemic burden of CHF patients with coronary
      artery disease.

PMID- 26205304
TI  - Impact of Personal Characteristics and Technical Factors on Quantification of
      Sodium 18F-Fluoride Uptake in Human Arteries: Prospective Evaluation of Healthy
      Subjects.
AB  - Sodium 18F-fluoride (18F-NaF) PET/CT imaging is a promising imaging technique for
      the assessment of atherosclerosis but is hampered by a lack of validated
      quantification protocols. Both personal characteristics and technical factors can
      affect quantification of arterial 18F-NaF uptake. This study investigated whether
      blood activity, renal function, injected dose, circulating time, and PET/CT
      system affect quantification of arterial 18F-NaF uptake. METHODS: Eighty-nine
      healthy subjects were prospectively examined by 18F-NaF PET/CT imaging. Arterial
      18F-NaF uptake was quantified at the level of the ascending aorta, aortic arch,
      descending thoracic aorta, and coronary arteries by calculating the maximum 18F
      NaF activity (NaFmax), the maximum/mean target-to-background ratio (TBRmax/mean),
      and the maximum blood-subtracted 18F-NaF activity (bsNaFmax). Multivariable
      linear regression assessed the effect of personal characteristics and technical
      factors on quantification of arterial 18F-NaF uptake. RESULTS: NaFmax and
      TBRmax/mean were dependent on blood activity (beta=0.34 to 0.44, P<0.001, and
      beta=-0.68 to -0.58, P<0.001, respectively) and PET/CT system (beta=-0.80 to 
      0.53, P<0.001, and beta=-0.80 to -0.23, P<0.031, respectively). bsNaFmax depended
      on PET/CT system (beta=-0.91 to -0.57, P<0.001) but not blood activity. This
      finding was observed at the level of the ascending aorta, aortic arch, descending
      thoracic aorta, and the coronary arteries. In addition to blood activity and
      PET/CT system, injected dose affected quantification of arterial 18F-NaF uptake,
      whereas renal function and circulating time did not. CONCLUSION: The prospective
      evaluation of 89 healthy subjects demonstrated that quantification of arterial
      18F-NaF uptake is affected by blood activity, injected dose, and PET/CT system.
      Therefore, blood activity, injected dose, and PET/CT system should be considered
      to generate accurate estimates of arterial 18F-NaF uptake.

PMID- 26205305
TI  - Protecting cognition from aging and Alzheimer's disease: a computerized cognitive
      training combined with reminiscence therapy.
AB  - OBJECTIVE: The aim of this paper was to assess the efficacy of process-based
      cognitive training (pb-CT) combined with reminiscence therapy (RT) in patients
      with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and in
      healthy elderly (HE) subjects. METHODS: This multicenter, randomized, controlled
      trial involved 348 participants with mAD, MCI, and HE from four European
      countries. Participants were randomly assigned to two arms of a crossover design:
      those in arm A underwent 3 months of computerized pb-CT for memory and executive
      functions combined with RT and 3 months of rest; those in arm B underwent the
      reverse. The primary outcome was the effect of the training on memory and
      executive functions performance. The secondary outcome was the effect of the
      training on functional abilities in mAD assessed with the instrumental activities
      of daily living. RESULTS: We found a significant effect of the training for
      memory in all three groups on delayed recall of the Rey Auditory Verbal Learning
      Test and for executive functions in HE on the phonological fluency test. MCI and
      HE participants maintained these effects at follow-up. MCI and mAD participants
      also showed a significant effect of the training on the Mini-mental state
      examination scale. Participants with mAD showed more stable instrumental
      activities of daily living during the training versus the rest period.
      CONCLUSIONS: Our results corroborate the positive effect of pb-CT and its
      maintenance primarily on memory in HE and MCI participants that did not seem to
      be potentiated by RT. Moreover, our results are very promising for the mAD
      participants.

PMID- 26205306
TI  - In silico analysis of SIGMAR1 variant (rs4879809) segregating in a consanguineous
      Pakistani family showing amyotrophic lateral sclerosis without frontotemporal
      lobar dementia.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting
      upper motor neurons in the brain and lower motor neurons in the brain stem and
      spinal cord, resulting in fatal paralysis. It has been found to be associated
      with frontotemporal lobar degeneration (FTLD). In the present study, we have
      described homozygosity mapping and gene sequencing in a consanguineous autosomal
      recessive Pakistani family showing non-juvenile ALS without signs of FTLD. Gene
      mapping was carried out in all recruited family members using microsatellite
      markers, and linkage was established with sigma non-opioid intracellular receptor
      1 (SIGMAR1) gene at chromosome 9p13.2. Gene sequencing of SIGMAR1 revealed a
      novel 3'-UTR nucleotide variation c.672*31A>G (rs4879809) segregating with
      disease in this family. The C9ORF72 repeat region in intron 1, previously
      implicated in a related phenotype, was excluded through linkage, and further
      confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with
      multiple primers in affected individuals and controls. In silico analysis was
      carried out to explore the possible role of 3'-UTR variant of SIGMAR1 in ALS. The
      Regulatory RNA motif and Element Finder program revealed disturbance in miRNA
      (hsa-miR-1205) binding site due to this variation. ESEFinder analysis showed new
      SRSF1 and SRSF1-IgM-BRCA1 binding sites with significant scores due to this
      variation. Our results indicate that the 3'-UTR SIGMAR1 variant c.672*31A>G may
      have a role in the pathogenesis of ALS in this family. 

PMID- 26205307
TI  - The whole picture: Holistic body posture recognition in infancy.
AB  - Holistic processing is tied to expertise and is characteristic of face and body
      perception by adults. Infants process faces holistically, but it is unknown
      whether they process body information holistically. In the present study, infants
      were tested for discrimination between body postures that differed in limb
      orientations in three conditions: in the context of the whole body, with just the
      isolated limbs that changed orientation, or with the limbs in the context of
      scrambled body parts. Five- and 9-month-olds discriminated between whole-body
      postures, but failed in the isolated-part and scrambled-body conditions,
      demonstrating holistic processing of information from bodies. These results
      indicate that at least some level of expertise in body processing develops quite
      early in life.

PMID- 26205309
TI  - Single-photon emitting diode in silicon carbide.
AB  - Electrically driven single-photon emitting devices have immediate applications in
      quantum cryptography, quantum computation and single-photon metrology. Mature
      device fabrication protocols and the recent observations of single defect systems
      with quantum functionalities make silicon carbide an ideal material to build such
      devices. Here, we demonstrate the fabrication of bright single-photon emitting
      diodes. The electrically driven emitters display fully polarized output, superior
      photon statistics (with a count rate of >300 kHz) and stability in both
      continuous and pulsed modes, all at room temperature. The atomic origin of the
      single-photon source is proposed. These results provide a foundation for the
      large scale integration of single-photon sources into a broad range of
      applications, such as quantum cryptography or linear optics quantum computing. 

PMID- 26205308
TI  - A lipidomic approach to the study of human CD4(+) T lymphocytes in multiple
      sclerosis.
AB  - BACKGROUND: Lipids play different important roles in central nervous system so
      that dysregulation of lipid pathways has been implicated in a growing number of
      neurodegenerative disorders including multiple sclerosis (MS). MS is the most
      prevalent autoimmune disorder of the central nervous system, with neurological
      symptoms caused by inflammation and demyelination. In this study, a lipidomic
      analysis was performed for the rapid profile of CD4(+) T lymphocytes from MS
      patient and control samples in an untargeted approach. METHODS: A matrix-assisted
      laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry based
      approach was used for the analysis of lipid extracts using 9-aminoacridine as
      matrix. Lipids were analyzed in negative mode and selected species fragmented
      using MALDI tandem mass spectrometry for their structural assignments. RESULTS:
      The analysis reveals some modifications in the phospholipid pattern of MS CD4(+)
      T lymphocytes with respect to healthy controls with a significant increase of
      cardiolipin species in MS samples. CONCLUSIONS: These results demonstrate the
      feasibility of a MALDI-TOF approach for the analysis of CD4(+) lipid extracts and
      suggest how alterations in the lipid metabolism characterized lymphocytes of MS
      patients.

PMID- 26205310
TI  - Perturbation of acyl ghrelin profile after liver transplantation.
AB  - BACKGROUND: A significant problem to be solved for patients after liver
      transplantation (LT) is malnutrition with anorexia in the early posttransplant
      period. We hypothesized that this problem was due to the change in ghrelin
      metabolism during LT. The aim of this study was to examine the balance of acyl
      ghrelin (AG) and desacyl ghrelin and the dependence of the regulation mechanism
      on hepatic-related enzymes in patients during LT. MATERIALS AND METHODS: AG,
      desacyl ghrelin, and acyl/total ghrelin (A/T) concentrations in blood samples
      were measured in 15 patients with liver failure (LF), 15 patients after LT, and
      10 controls. The correlations between the participants' ghrelin profiles and
      hepatic function-related data, including liver enzymes, were evaluated. In vitro
      assays using synthetic AG for assessment of deacylation activity in serum were
      performed. RESULTS: AG and A/T ratio were significantly higher in the LF patients
      than the patients after LT and controls (AG: 25.9 +/- 12.6 versus 16.4 +/- 12.6
      and 9.8 +/- 7.6 fmol/mL, P < 0.05; A/T ratio: 17.4 +/- 4.1 versus 12.2 +/- 5.5
      and 11.8% +/- 5.9%, P < 0.05). The serum cholinesterase level was inversely
      correlated with AG and A/T ratio (P < 0.01). In vitro assays showed that
      deacylation activity was significantly lower in patients with LF than controls
      (10.5% versus 42.4%, 90 min; P < 0.01). Degradation of AG was partially
      suppressed by a cholinesterase inhibitor. CONCLUSIONS: Deacylation activity was
      lower in LF patients, which could cause elevation of AG levels. Serum
      cholinesterase may be responsible for deacylation in humans.

PMID- 26205311
TI  - Multiorgan protection of remote ischemic perconditioning in valve replacement
      surgery.
AB  - BACKGROUND: Remote ischemic perconditioning (RIPerc) is a new alternative of
      remote ischemic conditioning and has not been well studied. RIPerc attenuates
      myocardial injury when applied during cardiac surgery. However, its protective
      effects on other organs remain unknown. MATERIALS AND METHODS: Patients with
      rheumatic heart disease undergoing valve replacement surgery were randomized into
      the RIPerc group (n = 101) or the control group (n = 100). RIPerc was achieved by
      three cycles of 5-min ischemia-5-min reperfusion in the right thigh during
      surgery. Clinical data and the levels of injury biomarkers for the heart, lungs,
      liver, and kidneys within 48 h after surgery were compared using one-way or
      repeated measurement analysis of variance. RESULTS: In the RIPerc group, the
      release of serum cardiac troponin I (128.68 +/- 102.56 versus 172.33 +/- 184.38,
      P = 0.04) and the inotropic score (96.4 +/- 73.8 versus 121.5 +/- 89.6, P =
      0.032) decreased compared with that of the control; postoperative drainage (458.2
      +/- 264.2 versus 545.1 +/- 349.0 ml, P = 0.048) and the incidence of acute lung
      injury was reduced (36.6% versus 51%, P = 0.04), and the extent of
      hyperbilirubinemia was also attenuated. No significant difference was observed in
      the levels of biomarkers for renal injury and systemic inflammation response.
      CONCLUSIONS: RIPerc applied during the valve replacement surgery induced multiple
      beneficial effects postoperatively including reduced drainage and myocardial
      damage, lower incidence of acute lung injury, and attenuated hyperbilirubinemia.

PMID- 26205312
TI  - Treatment of Creatine Transporter (SLC6A8) Deficiency With Oral S-Adenosyl
      Methionine as Adjunct to L-arginine, Glycine, and Creatine Supplements.
AB  - BACKGROUND: Creatine transporter (SLC6A8) deficiency is an X-linked inborn error
      of metabolism characterized by cerebral creatine deficiency, behavioral problems,
      seizures, hypotonia, and intellectual developmental disability. A third of
      patients are amenable to treatment with high-dose oral creatine, glycine, and L
      arginine supplementation. METHODS: Given the limited treatment response, we
      initiated an open-label observational study to evaluate the effect of adjunct S
      adenosyl methionine to further enhance intracerebral creatine synthesis. RESULTS:
      Significant and reproducible issues with sleep and behavior were noted in both
      male patients on a dose of 50/mg/kg. One of the two patients stopped S-adenosyl
      methionine and did not come for any follow-up. A safe and tolerable dose (17
      mg/kg/day) was identified in the other patient. On magnetic resonance
      spectroscopy, this 8-year-old male did not show an increase in intracerebral
      creatine. However, significant improvement in speech/language skills, muscle mass
      were observed as well as in personal outcomes as defined by the family in
      activities related to communication and decision making. DISCUSSION: Further
      research is needed to assess the potential of S-adenosyl methionine as an
      adjunctive therapy for creatine transporter deficiency patients and to define the
      optimal dose. Our study also illustrates the importance of pathophysiology-based
      treatment, individualized outcome assessment, and patient/family participation in
      rare diseases research.

PMID- 26205313
TI  - Social smoking among intermittent smokers.
AB  - BACKGROUND: "Social smoking" - smoking mostly or even only with others - may be
      an important pattern that implies smoking motivated extrinsically by social
      influences. Non-daily smokers (intermittent smokers; ITS) are often assumed to be
      social smokers, with some authors even assuming that all ITS are social smokers
      (SS+). We sought to identify and characterize social smokers in a sample of ITS.
      METHODS: 204 adult ITS (smoking 4-27 days/month) recorded the circumstances of
      smoking in their natural settings using Ecological Momentary Assessment, while
      also recording their circumstances in nonsmoking moments. SS+ were defined as ITS
      who were with others when they smoked most of their cigarettes, and who were
      >=50% more likely to be with others when smoking than when not. RESULTS: Only 13%
      of ITS were SS+. Although defined solely on the basis of presence of others, SS+
      showed a distinct pattern of smoking across multiple dimensions: compared to
      other ITS (who were significantly less likely to smoke when with others), SS+
      smoking was more associated with socializing, being with friends and
      acquaintances, drinking alcohol, weekends, evening or nighttime, being in other
      people's homes, but not their own home. SS+ smoking was low in the morning and
      increased in the evening. SS+ smoked fewer days/week and were less dependent, but
      did not differ demographically. CONCLUSIONS: Social smoking does constitute a
      highly distinct smoking pattern, but is not common among adult ITS.

PMID- 26205314
TI  - Recreational phenethylamine poisonings reported to a French poison control
      center.
AB  - OBJECTIVES: Over the last decade, use of phenethylamines has become increasingly
      prevalent. This study aimed to describe typical aspects of phenethylamine
      poisoning in order to better inform patient care. METHODS: Phenethylamine
      poisoning cases reported to the Poison Control Center of Angers, France, from
      January, 2007 to December, 2013 were examined. Clinical findings were examined in
      105 patients, including phenethylamine used, symptoms and final outcome. Patients
      were predominantly male (80%), with mean age 26+/-8 years. RESULTS: MDMA (38%),
      amphetamine (18%) and methamphetamine (14%) were the most commonly reported.
      Synthetic cathinones (10%) and the 2C series (7%) were also found. Substances
      most commonly associated with phenethylamine poisoning were cannabis (27%),
      ethanol (20%) and cocaine (9%). The most frequently reported symptoms included
      anxiety and hallucinations (49%), mydriasis and headache (41%), tachycardia (40%)
      and hypertension (15%). Complications such as seizures (7%), cardiac arrest (5%),
      toxic myocarditis (1%) and hemorrhagic stroke (1%) were also observed. Of the
      cases, the Poison Severity Score was: null or low, 66%, moderate, 21%, severe or
      fatal, 13%. Of the patients, 77% received hospital care and 12.4% were admitted
      to an intensive care unit. Analytical confirmations were obtained for all severe
      cases. While 93% of patients recovered, there were 5 deaths and 2 patients
      presented with neurological sequelae. CONCLUSIONS: Phenethylamine poisonings may
      be severe in young and healthy individuals. Physicians, toxicologists and
      analysts should be aware of new phenethylamine consumption trends in order to
      inform management of patient care and to contribute to a more responsive drug
      policy.

PMID- 26205315
TI  - Management of benzodiazepine-resistant alcohol withdrawal across a healthcare
      system: Benzodiazepine dose-escalation with or without propofol.
AB  - BACKGROUND: Severe cases of alcohol withdrawal syndrome (AWS) may not resolve
      despite escalating doses of benzodiazepines (BZDs). Benzodiazepine-resistant
      alcohol withdrawal (RAW) is a subset of severe alcohol withdrawal defined by the
      requirement of >=40mg of diazepam administered within one hour. Use of adjunct
      agents, such as propofol, may be beneficial to minimize BZD adverse effects and
      improve symptom control. While limited evidence suggests propofol as an effective
      adjunct in AWS through improved sedation, evidence is currently lacking for the
      addition of only propofol to BZDs for management of RAW. METHODS: Retrospective
      review of adult patients from January, 2009 to March, 2012 with RAW. Patients
      were categorized into BZD dose-escalation only or BZD plus propofol. The primary
      endpoint was time to resolution of AWS. Secondary endpoints included safety
      outcomes associated with medication use. RESULTS: Of 1083 patients with severe
      AWS, 66 RAW patients (n=33 BZD only, n=33 BZD plus propofol) met inclusion.
      Median time to AWS resolution was 5.0 and 7.0 days for BZD only vs. BZD plus
      propofol (p=0.025). Duration of mechanical ventilation, ICU and hospital length
      of stay were significantly higher with propofol (p=0.017, <0.001 and <0.001,
      respectively). Ten patients required intervention for management of propofol
      induced adverse reactions. CONCLUSIONS: The addition of propofol for RAW
      treatment is associated with significant increases in clinical care. While
      randomized, prospective evaluations are necessary to determine the cause of this
      association, our data suggests use of adjunctive propofol therapy in RAW is
      associated with longer and more complicated hospital admissions.

PMID- 26205316
TI  - Monte Carlo modeling of a conventional X-ray computed tomography scanner for gel
      dosimetry purposes.
AB  - Our purpose in the current study was to model an X-ray CT scanner with the Monte
      Carlo (MC) method for gel dosimetry. In this study, a conventional CT scanner
      with one array detector was modeled with use of the MCNPX MC code. The MC
      calculated photon fluence in detector arrays was used for image reconstruction of
      a simple water phantom as well as polyacrylamide polymer gel (PAG) used for
      radiation therapy. Image reconstruction was performed with the filtered back
      projection method with a Hann filter and the Spline interpolation method. Using
      MC results, we obtained the dose-response curve for images of irradiated gel at
      different absorbed doses. A spatial resolution of about 2 mm was found for our
      simulated MC model. The MC-based CT images of the PAG gel showed a reliable
      increase in the CT number with increasing absorbed dose for the studied gel.
      Also, our results showed that the current MC model of a CT scanner can be used
      for further studies on the parameters that influence the usability and
      reliability of results, such as the photon energy spectra and exposure techniques
      in X-ray CT gel dosimetry. 

PMID- 26205317
TI  - Should the pharmacological actions of dietary fatty acids in cardiometabolic
      disorders be classified based on biological or chemical function?
AB  - Westernised dietary patterns are characterised by an increased intake of
      saturated (SFA) and trans fat (TFA) and a high n-6:n-3 polyunsaturated fatty acid
      (PUFA) ratio. These changes together with increased sugar intake have been
      implicated in the progression and development of metabolic syndrome. It is now
      recognised that the type of dietary fat plays a far more significant role in well
      being than the absolute amount. This has led to the generalisations that TFA and
      SFA are detrimental, MUFA is neutral and PUFA is cardioprotective. However,
      different dietary fatty acids even within the same chemical class elicit
      different physiological responses. Thus, generalising fatty acids by the degree
      of unsaturation or the configuration of double bonds alone is unlikely to predict
      biological responses. In this review, we have examined the effects of different
      dietary fatty acids on the cardiometabolic risk factors and propose a revised
      classification based on current evidence of biological activity, rather than
      chemical structure. Specifically, we propose that dietary fatty acids be
      classified into five classes as neutral, reduce one or more cardiometabolic risk
      factors, increase one or more cardiometabolic risk factor, controversial evidence
      to allow classification and inadequate research to allow classification as a
      basis for further discussions. 

PMID- 26205318
TI  - Successful aging at 100 years: the relevance of subjectivity and psychological
      resources.
AB  - BACKGROUND: Very old individuals seem to present an admirable capacity to
      overcome adversities and adapt to the challenges of advanced age. However,
      studies focusing successful pattern of centenarians found that they may easily
      fail to be categorized as successful agers when objective criteria are applied.
      The present study examines if centenarians can be considered successful agers.
      Following Rowe and Kahn's successful aging model, the primary goal was to clarify
      whether centenarians are able to be successful agers according to objective and
      subjective criteria of no major disease and disability, high cognitive and
      physical functioning and engagement with life. The second goal was to investigate
      whether socio-demographic factors, psychological, social, and economic resources
      are related to objective and subjective successful aging profiles. METHODS: We
      examined different profiles of successful aging in a high selected sample of
      individuals aged 100 and more years old from the population-based Oporto
      Centenarian Study. RESULTS: Main findings reveal that centenarians do not
      represent the prototype of successful aging, but self-ratings demonstrate that
      many of them feel successful, despite not being objectively considered as so.
      Those who were considered successful agers presented higher values of self
      efficacy, hope, and purpose in life, as well as few difficulties in covering
      financial expenses. CONCLUSIONS: As a basis for strengthening the existing model,
      the value of subjectivity should be explored and psychological resources promoted
      in interventions to foster positive adaptation in very old age.

PMID- 26205319
TI  - Correction: Kinetics and mechanism of the reaction of perfluoro propyl vinyl
      ether (PPVE, C3F7OCH[double bond, length as m-dash]CH2) with OH: assessment of
      its fate in the atmosphere.
AB  - Correction for 'Kinetics and mechanism of the reaction of perfluoro propyl vinyl
      ether (PPVE, C3F7OCH[double bond, length as m-dash]CH2) with OH: assessment of
      its fate in the atmosphere' by D. Amedro et al., Phys. Chem. Chem. Phys., 2015,
      17, 18558-18566. 

PMID- 26205320
TI  - Divergence between dietary folate intake and concentrations in the serum and red
      blood cells of aging males in the United States.
AB  - BACKGROUND & AIMS: As part of a broader study examining the relationship between
      serum folate concentrations and prostate cancer progression, we determined if
      there are age related changes in serum folate concentration compared to folate
      intake in the U.S. male population. METHODS: Weighted data from the 2007-2008 and
      2009-2010 NHANES databases was analyzed. A subpopulation of male participants was
      selected who were older than one year of age, had completed two days of dietary
      recall including supplement usage, and had fasted for at least 4 h prior to
      having their serum folate measured. Total dietary folate equivalent (DFE) intake
      (mcg) represented the combination of all natural food folate and folic acid from
      fortification and dietary supplements. Geometric means of serum folate (nM), red
      blood cell (RBC) folate (nM), and DFE intake were calculated for nine consecutive
      age groups, with each group generally representing a 10 year span. Analysis was
      then focused on males older than 20 years of age. RESULTS: A total of 19,142
      subjects were in the initial NHANES population, which represented over 294
      million people within the United States. Applying our inclusion criteria created
      a final subpopulation size of 3775. Subsequent analysis of the age groups for all
      males older than 20 years found the following: The mean serum folate (nM) with
      95% CI levels ranged from 28.2 (26.6, 29.9) to 55.1 (47.5, 63.9). RBC folate (nM)
      concentrations with 95% CI levels without any fasting exclusions ranged from
      795.6 (741.5, 853.7) to 1038.4 (910.7, 1184.2). Serum and RBC folate
      concentrations were significantly higher with age across these age groups (p <
      0.001). However, the mean total daily DFE intake did not significantly differ
      ranging from 640.4 (574.7, 713.7) to 720.2 (665, 780) mcg, (p = 0.373). Serum
      folate concentrations in men with total daily DFE intake of at least 1000 mcg
      increased more significantly with increasing age than serum folate concentrations
      in men with less than 400 mcg of total daily DFE intake (p < 0.001). There was a
      similar trend with the RBC folate concentrations (p = 0.054). CONCLUSIONS: We
      observed higher serum and RBC folate concentrations and a divergence between
      dietary folate intake and these folate concentrations in older males. This
      phenomenon was evident at total DFE intakes that were significantly less than the
      1000 mcg tolerable upper intake level currently recommended by the Institute of
      Medicine.

PMID- 26205322
TI  - Morphometric characteristics of caudal cranial nerves at petroclival region in
      fetuses.
AB  - Morphometric measurements of cranial nerves in posterior cranial fossa of fetus
      cadavers were carried out in an attempt to identify any asymmetry in their
      openings into the cranium. Twenty-two fetus cadavers (8 females, 14 males) with
      gestational age ranging between 22 and 38 weeks (mean 30 weeks) were included in
      this study. The calvaria were removed, the brains were lifted, and the cranial
      nerves were identified. The distance of each cranial nerve opening to midline and
      the distances between different cranial nerve openings were measured on the left
      and right side and compared. The mean clivus length and width were 21.2 +/- 4.4
      and 13.2 +/- 1.5 mm, respectively. The distance of the twelfth cranial nerve
      opening from midline was shorter on the right side when compared with the left
      side (6.6 +/- 1.1 versus 7.1 +/- 0.8 mm, p = 0.038). Openings of other cranial
      nerves did not show such asymmetry with regard to their distance from midline,
      and the distances between different cranial nerves were similar on the left and
      right side. Cranial nerves at petroclival region seem to show minimal asymmetry
      in fetuses. 

PMID- 26205323
TI  - Definitive Endoderm Differentiation of Human Embryonic Stem Cells Combined with
      Selective Elimination of Undifferentiated Cells by Methionine Deprivation.
AB  - Human embryonic stem cells (ESCs) show a characteristic feature in that they are
      highly dependent on methionine metabolism. Undifferentiated human ESCs cannot
      survive under condition that methionine is deprived from culture medium. We
      describe here a procedure for definitive endoderm differentiation from human
      ESCs, in which human ESCs are subject to 10 days' (d) differentiation combined
      with methionine deprivation between differentiation days (d) 8 to (d) 10.
      Methionine deprivation results in elimination of undifferentiated cells from the
      culture with no significant loss of definitive endoderm cells, as compared to
      those cultured under complete condition throughout the whole culture period. 

PMID- 26205321
TI  - Sarcopenia is associated with an increased inflammatory response to surgery in
      colorectal cancer.
AB  - BACKGROUND & AIMS: Sarcopenia in gastrointestinal cancer has been associated with
      poor clinical outcome after surgery. The effect of low muscle mass on the
      inflammatory response to surgery has not been investigated, however skeletal
      muscle wasting in the context of cachexia is associated with a hyperinflammatory
      state at baseline. Knowledge on this matter can provide new insight into the
      detrimental effects of sarcopenia on postoperative recovery, possibly leading to
      novel therapeutic strategies. The aim of this study was to evaluate whether low
      muscle mass is associated with increased inflammation after resection of
      colorectal malignancies. METHODS: Eighty-seven consecutive patients undergoing
      elective resection of a primary colorectal tumor were enrolled. Muscle mass was
      assessed on routine preoperative computed tomography (CT) scans using image
      analysis by Osirix((r)) by measuring skeletal muscle at the third lumbar vertebra
      (L3) level. The effect of muscle mass on pre- and postoperative plasma
      concentrations of C-reactive protein (CRP), calprotectin and interleukin-6 (IL-6)
      was analyzed. Clinical outcome was assessed by HARM (HospitAl stay, Readmission,
      and Mortality) scores. RESULTS: Skeletal muscle mass was not predictive of plasma
      concentrations of CRP and IL-6. However, low skeletal muscle mass was
      significantly predictive of high plasma concentrations of calprotectin on
      postoperative days (POD) 2 through 5, reaching highest significance on POD4
      (regression beta, -6.06; 95% confidence interval, -10.45 to -1.68; p = 0.007).
      CONCLUSIONS: Low muscle mass in patients undergoing surgery for colorectal cancer
      was associated with an increased postoperative inflammatory response. This may be
      at least part of the explanation for the high incidence of postoperative
      complications in sarcopenic patients.

PMID- 26205324
TI  - Novel immobilization process of a thermophilic catalase: efficient purification
      by heat treatment and subsequent immobilization at high temperature.
AB  - The main goal of the present work is to investigate a novel process of
      purification and immobilization of a thermophilic catalase at high temperatures.
      The catalase, originated from Bacillus sp., was overexpressed in a recombinant
      Escherichia coli BL21(DE3)/pET28-CATHis and efficiently purified by heat
      treatment, achieving a threefold purification. The purified catalase was then
      immobilized onto an epoxy support at different temperatures (25, 40, and 55 
      degrees C). The immobilizate obtained at higher temperatures reached its maximum
      activity in a shorter time than that obtained at lower temperatures. Furthermore,
      immobilization at higher temperatures required a lower ionic strength than
      immobilization at lower temperatures. The characteristics of immobilized enzymes
      prepared at different temperatures were investigated. The high-temperature
      immobilizate (55  degrees C) showed the highest thermal stability, followed by
      the 40  degrees C immobilizate. And the high-temperature immobilizate (55 
      degrees C) had slightly higher operational stability than the 25  degrees C
      immobilizate. All of the immobilized catalase preparations showed higher
      stability than the free enzyme at alkaline pH 10.0, while the alkali resistance
      of the 25  degrees C immobilizate was slightly better than that of the 40 and 55 
      degrees C immobilizates. 

PMID- 26205325
TI  - Does intravenous atropine affect stroke volume variation in man?
AB  - OBJECTIVES: Currently there are no reports of the effect of increasing heart rate
      (HR) induced by intravenous atropine on stroke volume variation (SVV). We
      hypothesized that increasing HR alters the value of SVV. This prospective study
      aimed to investigate changes in SVV values by increasing HR induced by
      intravenous atropine in patients with good cardiac function. We also re-evaluated
      the effect of intravenous atropine alone on hemodynamics including new
      hemodynamic parameters such as SVV. METHODS: Patients were chosen as participants
      of this study if, 30 minutes after anesthesia induction, HR was below 65
      beats/min. Baseline hemodynamic values were recorded, and then the patients
      received intravenous atropine (0.01 mg/kg; max 0.5 mg). These values were
      recorded again after intravenous atropine every minute for 5 minutes. RESULTS:
      Ten American Society of Anesthesiologists (ASA) physical status I-II patients
      aged 37-65 years who were scheduled for elective surgery were included.
      Intravenous atropine significantly increased HR at the 1-5 minute time points,
      mean arterial pressure at the 1-4 minute time points, and cardiac output at the 1
      3 minute time points compared with baseline values but did not significantly
      change SVV, stroke volume index, pressure of end-tidal CO2, and systemic vascular
      resistance. CONCLUSION: Administration of intravenous atropine did not change
      SVV, and we present this as a novel finding.

PMID- 26205326
TI  - The unique role of transdermal buprenorphine in the global chronic pain epidemic.
AB  - Pain is a global epidemic, exacerbated by barriers to access of opioid
      analgesics. Regulations about opioids attempt to protect public health from the
      risks of harmful use of opioids, diversion, and dependence. Transdermal
      buprenorphine is an effective opioid analgesic agent with unique properties that
      may make it particularly well suited for more widespread use. It is a versatile
      analgesic product with demonstrated safety and effectiveness in cancer and
      noncancer pain populations. Its pharmacological properties make it a first-line
      opioid analgesic for geriatric patients and patients with renal dysfunction; no
      dosing adjustments need to be made. The 7-day transdermal delivery system is
      convenient for patients and promotes compliance. A low dose of buprenorphine can
      provide effective and well-tolerated pain relief. Although buprenorphine has been
      associated with certain opioid-related adverse effects, such as dizziness and
      nausea, it is associated with a lower rate of constipation than many other opioid
      analgesics. The potential for nonmedical use of buprenorphine is relatively low
      compared with other opioid agents. Buprenorphine has a relatively low likeability
      for nonmedical use and the transdermal matrix patch renders the substance
      particularly difficult to extract for illicit purposes. 

PMID- 26205327
TI  - Skating on thin ice: pragmatic prescribing for medication refractory
      schizophrenia.
AB  - BACKGROUND: Clozapine is the treatment of choice for medication refractory
      psychosis, but it does not benefit half of those put on it. There are numerous
      studies of potential post-clozapine strategies, but little data to guide the
      order of such treatment in this common clinical challenge. We describe a
      naturalistic observational study in 153 patients treated by a specialist
      psychosis service to identify optimal pharmacotherapy practice, based on
      outcomes. METHODS: Medication and clinical data, based on the OPCRIT tool, were
      examined on admission and discharge from the national psychosis service. The
      primary outcome measure was the percentage change in mental state examination
      symptoms between admission and discharge and the association with medication on
      discharge. Exploratory analyses evaluated the specificity of individual
      medication effects on symptom clusters. RESULTS: There were fewer drugs
      prescribed at discharge relative to admission, suggesting an optimisation of
      medication, and a doubling of the number of patients treated with clozapine.
      Treatment with clozapine on discharge was associated with maximal decrease in
      symptoms from admission. In the group of patients that did not respond to
      clozapine monotherapy, the most effective drug combinations were clozapine
      augmentation with 1) sodium valproate, 2) lithium, 3) amisulpride, and 4)
      quetiapine. There was no support for a dose-response relationship for any drug
      combination. CONCLUSIONS: Clozapine monotherapy is clearly the optimal medication
      in medication refractory schizophrenia and it is possible to maximise its use. In
      patients unresponsive to clozapine monotherapy, augmentation with sodium
      valproate, lithium, amisulpride and quetiapine, in that order, is a reasonable
      treatment algorithm. Reducing the number of ineffective drugs is possible without
      a detrimental effect on symptoms. Exploratory data indicated that clozapine was
      beneficial across a range of symptoms domains, whereas olanzapine was beneficial
      specifically for hallucinations and lamotrigine for comorbid affective symptoms.

PMID- 26205330
TI  - 'Thank You, Doctor' Says It All.

PMID- 26205329
TI  - HCV infection is associated with lower survival in simultaneous liver kidney
      transplant recipients in the United States.
AB  - BACKGROUND: The frequency of simultaneous liver kidney transplantation (SLKT) has
      been increasing over the past decade. Hepatitis C virus (HCV) infection is the
      most common indication for liver transplantation in the United States. Given the
      rising prevalence of HCV-related SLKT, it is important to understand the impact
      of HCV in this patient population. METHODS: We conducted a retrospective cohort
      study using data from the United Network for Organ Sharing registry to assess
      adult patients undergoing SLKT in the United States from 2003 to 2012. Patient
      survival following SLKT was assessed using Kaplan-Meier methods and multivariate
      Cox proportional hazards models. RESULTS: Patients infected with non-HCV have
      significantly lower survival following SLKT compared to non-HCV patients at three
      (three-yr survival: 71.0% vs. 78.9%, p < 0.01) and five yr (five-yr survival:
      61.4% vs. 72.5%, p < 0.01). The results of multivariate regression analyses
      demonstrated that patients infected with HCV had significantly lower survival
      following SLKT than patients with non-HCV disease (HR 1.41, 95% CI, 1.19-1.67, p
      < 0.001). In addition, lower post-SLKT survival was noted among patients with
      diabetes (HR 1.34, 95% CI, 1.13-1.58, p < 0.001) and hepatocellular carcinoma (HR
      1.60, 95% CI, 1.17-2.18, p < 0.01). CONCLUSIONS: Hepatitis C infection is
      associated with lower patient survival following SLKT.

PMID- 26205328
TI  - Reactivating mutant p53 using small molecules as zinc metallochaperones:
      awakening a sleeping giant in cancer.
AB  - Tumor protein p53 (TP53) is the most commonly mutated gene in human cancer. The
      majority of mutations are missense, and generate a defective protein that is
      druggable. Yet, for decades, the small-molecule restoration of wild-type (WT) p53
      function in mutant p53 tumors (so-called p53 mutant 'reactivation') has been
      elusive to researchers. The p53 protein requires the binding of a single zinc ion
      for proper folding, and impairing zinc binding is a major mechanism for loss of
      function in missense mutant p53. Here, we describe recent work defining a new
      class of drugs termed zinc metallochaperones that restore WT p53 structure and
      function by restoring Zn(2+) to Zn(2+)-deficient mutant p53.

PMID- 26205331
TI  - Unexpected Venous Thrombosis in the Superior Vena Cava.

PMID- 26205332
TI  - Palm Reading, Observation, and Intuition.

PMID- 26205333
TI  - What have we learned from global change manipulative experiments in China? A meta
      analysis.
AB  - Although China has the largest population in the world, a faster rate of warming
      than the global average, and an active global change research program, results
      from many of the global change experiments in Chinese terrestrial ecosystems have
      not been included in global syntheses. Here, we specifically analyze the observed
      responses of carbon (C) and nitrogen (N) cycling in global change manipulative
      experiments in China, and compare these responses to those from other regions of
      the world. Most global change factors, vegetation types, and treatment methods
      that have been studied or used elsewhere in the world have also been studied and
      applied in China. The responses of terrestrial ecosystem C and N cycles to N
      addition and climate warming in China are similar in both direction and intensity
      to those reported in global syntheses. In Chinese ecosystems as elsewhere, N
      addition significantly increased aboveground (AGB) and belowground biomass (BGB),
      litter mass, dissolved organic C, net ecosystem productivity (NEP), and gross
      ecosystem productivity (GEP). Warming stimulated AGB, BGB and the root-shoot
      ratio. Increasing precipitation accelerated GEP, NEP, microbial respiration, soil
      respiration, and ecosystem respiration. Our findings complement and support
      previous global syntheses and provide insight into regional responses to global
      change. 

PMID- 26205334
TI  - Diagnosis: Fishing for exosomes.

PMID- 26205335
TI  - Metabolism: Mutant BRAF feels the burn.

PMID- 26205336
TI  - Breast cancer: Untangling the role of progesterone receptors.

PMID- 26205342
TI  - Resveratrol and derivatives for the treatment of atrial fibrillation.
AB  - Resveratrol is a bioactive polyphenol, found in grapes, red wine, and peanuts,
      and has recently garnered much media and scientific attention for its diverse
      beneficial health effects as a nutritional supplement or nutraceutical. Of
      particular interest are the well-documented cardioprotective effects of
      resveratrol that are mediated by diverse mechanisms, including its antioxidant
      and vascular effects. However, it is now becoming clear that resveratrol may also
      exhibit direct effects on cardiac function and rhythm through modulation of
      signaling pathways that regulate cardiac remodeling and ion channel activity that
      controls cardiac excitability. Resveratrol may therefore possess antiarrhythmic
      properties that contribute to the cardiovascular benefits of resveratrol. Atrial
      fibrillation (AF) is the most common cardiac arrhythmia, although current
      therapies are suboptimal. Our laboratory has been studying resveratrol's effects
      on cardiac ion channels and remodeling pathways, and we initiated a drug
      development program aimed at generating novel resveratrol derivatives with
      improved efficacy against AF when compared to currently available therapeutics.
      This review therefore focuses on the effects of resveratrol and new derivatives
      on a variety of cardiac ion channels and molecular pathways that contribute to
      the development and maintenance of atrial fibrillation. 

PMID- 26205340
TI  - Evolving synergistic combinations of targeted immunotherapies to combat cancer.
AB  - Immunotherapy has now been clinically validated as an effective treatment for
      many cancers. There is tremendous potential for synergistic combinations of
      immunotherapy agents and for combining immunotherapy agents with conventional
      cancer treatments. Clinical trials combining blockade of cytotoxic T lymphocyte
      associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) may serve
      as a paradigm to guide future approaches to immuno-oncology combination therapy.
      In this Review, we discuss progress in the synergistic design of immune-targeting
      combination therapies and highlight the challenges involved in tailoring such
      strategies to provide maximal benefit to patients. 

PMID- 26205343
TI  - What do patients bring up in consultations? An observational study in general
      practice.
AB  - OBJECTIVE: The main aim of the study was to investigate how many and what kind of
      problems patients present in consultations with their general practitioner (GP).
      A secondary aim was to explore patients' views on what is important in
      consultations. DESIGN: Cross-sectional study including observation of unselected
      consultations with recording on a pre-designed scheme, and a brief questionnaire
      filled in by patients. SETTING: Four general practices in Oslo, Norway. SUBJECTS:
      A total of 201 patients in consultations and 177 patients waiting to see their
      GP. MAIN OUTCOME MEASURES: Number and characteristics of problems raised by
      patients, and whether the problems were handled by GPs during the ongoing
      consultation. Patients' expectations for the consultation. RESULTS: The mean
      number of problems raised was 2.6 (range 1-16), and when appointments for acute
      conditions were excluded, the mean number was 3.3. Somatic problems comprised
      about half of all problems, and in more than one-quarter of consultations a
      mental health issue was presented. Female sex and increasing age predicted an
      increasing number of problems raised. In one-quarter of encounters four or more
      problems were presented. The vast majority of problems were dealt with by the GPs
      during the ongoing consultation. "That I am able to address all the problems I
      have" was rated as highly important by patients. CONCLUSION: GPs deal with
      multiple and unrelated problems in daily consultations, which is highly valued by
      patients. Management of concurrent problems in brief encounters demands training
      and adequate working conditions, in order to sustain this core value of general
      practice.

PMID- 26205341
TI  - Adiposity and cancer risk: new mechanistic insights from epidemiology.
AB  - Excess body adiposity, commonly expressed as body mass index (BMI), is a risk
      factor for many common adult cancers. Over the past decade, epidemiological data
      have shown that adiposity-cancer risk associations are specific for gender, site,
      geographical population, histological subtype and molecular phenotype. The
      biological mechanisms underpinning these associations are incompletely understood
      but need to take account of the specificities observed in epidemiology to better
      inform future prevention strategies. 

PMID- 26205344
TI  - Patients, health information, and guidelines: A focus-group study.
AB  - BACKGROUND: Evidence-based clinical guidelines could support shared decision
      making and help patients to participate actively in their care. However, it is
      not well known how patients view guidelines as a source of health information.
      This qualitative study aimed to assess what patients know about guidelines, and
      what they think of their presentation formats. RESEARCH QUESTION: What is the
      role of guidelines as health information for patients and how could the
      implementation of evidence-based information for patients be improved? METHODS: A
      qualitative study with focus groups that were built around a semi-structured
      topic guide. Focus groups were audiotaped and transcribed and analysed using a
      phenomenographic approach. RESULTS: Five focus groups were carried out in 2012
      with a total of 23 participants. Patients searched for health information from
      the Internet or consulted health professionals or their personal networks. The
      concepts of guidelines included instructions or standards for health
      professionals, information given by a health professional to the patient, and
      material to protect and promote the interests of patients. Some patients did not
      have a concept for guidelines. Patients felt that health information was abundant
      and its quality sometimes difficult to assess. They respected conciseness,
      clarity, clear structure, and specialists or well-known organizations as authors
      of health information. Patients would like health professionals to deliver and
      clarify written materials to them or point out to them the relevant Internet
      sites. CONCLUSIONS: The concept of guidelines was not well known among our
      interviewees; however, they expressed an interest in having more communication on
      health information, both written information and clarifications with their health
      professionals.

PMID- 26205345
TI  - Admission serum magnesium levels and the risk of acute respiratory failure.
AB  - BACKGROUND: The association between admission serum magnesium (Mg) levels and
      risk of acute respiratory failure (ARF) in hospitalised patients is limited. The
      aim of this study was to assess the risk of developing ARF in all hospitalised
      patients with various admission Mg levels. METHODS: This is a single-center
      retrospective study conducted at a tertiary referral hospital. All hospitalised
      adult patients who had admission Mg available from January to December 2013 were
      analysed in this study. Admission Mg was categorised based on its distribution
      into six groups (less than 1.5, 1.5-1.7, 1.7-1.9, 1.9-2.1, 2.1-2.3 and greater
      than 2.3 mg/dl). The primary outcome was in-hospital ARF occurring after hospital
      admission. Logistic regression analysis was performed to obtain the odds ratio of
      ARF of various admission Mg levels using Mg of 1.7-1.9 mg/dl as the reference
      group. RESULTS: Of 9780 patients enrolled, ARF occurred in 619 patients (6.3%).
      The lowest incidence of ARF was when serum Mg within 1.7-1.9 mg/dl. A U-shaped
      curve emerged demonstrating higher incidences of ARF associated with both
      hypomagnesemia (< 1.7) and hypermagnesemia (> 1.9). After adjusting for potential
      confounders, both hypomagnesemia (< 1.5 mg/dl) and hypermagnesemia (> 2.3 mg/dl)
      were associated with an increased risk of developing ARF with odds ratios of 1.69
      (95% CI: 1.19-2.36) and 1.40 (95% CI: 1.02-1.91) respectively. CONCLUSION: Both
      admission hypomagnesemia and hypermagnesemia were associated with an increased
      risk for in-hospital ARF.

PMID- 26205346
TI  - Bis(monoacylglycero)phosphate as a Macrophage Enriched Phospholipid.
AB  - Bis(monoacylglycero)phosphate (BMP) is a structural isomer of
      phosphatidylglycerol (PtdGro) with an unusual sn-1:sn-1' fatty acyl configuration
      and is found almost exclusively in late endosomes/lysosomes. BMP comprises only
      about 1-2% of the total phospholipids in most mammalian cells, but accumulates in
      tissues of humans and animals with lysosomal storage disorders including the
      gangliosidoses. Total BMP content was significantly greater in cells of
      macrophage/microglial origin than in cells of macroglial origin. BMP composition
      was similar in tumorigenic/metastatic macrophages and non-tumorigenic
      macrophages/microglia. Finally, BMP fatty acid composition differed between cells
      grown in culture and obtained in vivo suggesting an influence from growth
      environment.

PMID- 26205347
TI  - Inhibition of class I histone deacetylases by romidepsin potently induces Epstein
      Barr virus lytic cycle and mediates enhanced cell death with ganciclovir.
AB  - Pan-histone deacetylase (HDAC) inhibitors, which inhibit 11 HDAC isoforms, are
      widely used to induce Epstein-Barr virus (EBV) lytic cycle in EBV-associated
      cancers in vitro and in clinical trials. Here, we hypothesized that inhibition of
      one or several specific HDAC isoforms by selective HDAC inhibitors could potently
      induce EBV lytic cycle in EBV-associated malignancies such as nasopharyngeal
      carcinoma (NPC) and gastric carcinoma (GC). We found that inhibition of class I
      HDACs, particularly HDAC-1, -2 and -3, was sufficient to induce EBV lytic cycle
      in NPC and GC cells in vitro and in vivo. Among a panel of selective HDAC
      inhibitors, the FDA-approved HDAC inhibitor romidepsin was found to be the most
      potent lytic inducer, which could activate EBV lytic cycle at ~0.5 to 5 nM
      (versus ~800 nM achievable concentration in patients' plasma) in more than 75% of
      cells. Upregulation of p21(WAF1) , which is negatively regulated by class I
      HDACs, was observed before the induction of EBV lytic cycle. The upregulation of
      p21(WAF1) and induction of lytic cycle were abrogated by a specific inhibitor of
      PKC-delta but not the inhibitors of PI3K, MEK, p38 MAPK, JNK or ATM pathways.
      Interestingly, inhibition of HDAC-1, -2 and -3 by romidepsin or shRNA knockdown
      could confer susceptibility of EBV-positive epithelial cells to the treatment
      with ganciclovir (GCV). In conclusion, we demonstrated that inhibition of class I
      HDACs by romidepsin could potently induce EBV lytic cycle and mediate enhanced
      cell death with GCV, suggesting potential application of romidepsin for the
      treatment of EBV-associated cancers. 

PMID- 26205348
TI  - Fluoxetine increases plasticity and modulates the proteomic profile in the adult
      mouse visual cortex.
AB  - The scarce functional recovery of the adult CNS following injuries or diseases is
      largely due to its reduced potential for plasticity, the ability to reorganize
      neural connections as a function of experience. Recently, some new strategies
      restoring high levels of plasticity in the adult brain have been identified,
      especially in the paradigmatic model of the visual system. A chronic treatment
      with the anti-depressant fluoxetine reinstates plasticity in the adult rat
      primary visual cortex, inducing recovery of vision in amblyopic animals. The
      molecular mechanisms underlying this effect remain largely unknown. Here, we
      explored fluoxetine effects on mouse visual cortical plasticity, and exploited a
      proteomic approach to identify possible candidates mediating the outcome of the
      antidepressant treatment on adult cortical plasticity. We showed that fluoxetine
      restores ocular dominance plasticity in the adult mouse visual cortex, and
      identified 31 differentially expressed protein spots in fluoxetine-treated
      animals vs. controls. MALDITOF/TOF mass spectrometry identification followed by
      bioinformatics analysis revealed that these proteins are involved in the control
      of cytoskeleton organization, endocytosis, molecular transport, intracellular
      signaling, redox cellular state, metabolism and protein degradation. Altogether,
      these results indicate a complex effect of fluoxetine on neuronal signaling
      mechanisms potentially involved in restoring plasticity in the adult brain.

PMID- 26205349
TI  - Molecular cloning and characterization of the gonadotropin subunits GPalpha,
      FSHbeta, and LHbeta genes in the stinging catfish Heteropneustes fossilis:
      phylogeny, seasonal expression and pituitary localization.
AB  - Gonadotropins are heterodimeric glycoproteins secreted by the pituitary, and
      consist of a common glycoprotein hormone alpha (GPalpha) and the function
      specific follicle-stimulating hormone beta subunit (FSHbeta) or luteinizing
      hormone beta subunit (LHbeta). In the present study, the subunit protein genes
      were cloned and characterized from the pituitary of the catfish Heteropneustes
      fossilis. Full-length cDNAs of GPalpha, FSHbeta, and LHbeta are 511 base pairs
      (bp), 659 bp and 660 bp long, and encode 92, 108, and 112 aminoacids long mature
      proteins, respectively. GPalpha has 10 cysteines with 2 N-linked glycosylation
      sites while LHbeta contains 12 cysteines with a single N-linked glycosylation
      site. In contrast, FSHbeta has 13 cysteines, 1 additional over the conserved 12
      cysteines of other vertebrates, and a single glycosylation site between Cys 3 and
      Cys 4. Phylogenetic analyses of the deduced proteins confirm their homology and
      relationships with the respective gonadotropin subunit proteins of gnathostome
      vertebrates. Tissue expression analysis by semi-quantitative RT-PCR shows that
      GPalpha mRNA is expressed only in the pituitary while both FSHbeta and LHbeta
      mRNA are expressed in extra-pituitary sites. The subunit mRNAs show both seasonal
      and sex dimorphic variations especially in the expression of FSHbeta and LHbeta
      transcripts. In the sexually quiescent phase, the transcript expression is low
      while in the recrudescent phase, the expressions are differential, high, and
      varied with regard to sex and reproductive phase. In situ hybridization of the
      mRNAs gave positive signals in gonadotropes in the pars distalis of the
      pituitary, which exhibited seasonal variation in staining intensity and numbers.

PMID- 26205350
TI  - Response surface methodology for the optimization of dispersive liquid-liquid
      microextraction of chloropropanols in human plasma.
AB  - Chloropropanols are processing toxicants with a potential risk to human health
      due to the increased intake of processed foods. A rapid and efficient method for
      the determination of three chloropropanols in human plasma was developed using
      ultrasound-assisted dispersive liquid-liquid microextraction. The method involved
      derivatization and extraction in one step followed by gas chromatography with
      tandem mass spectrometry analysis. Parameters affecting extraction, such as
      sample pH, ionic strength, type and volume of dispersive and extraction solvents
      were optimized by response surface methodology using a pentagonal design. The
      linear range of the method was 5-200 ng/mL for 1,3-dichloro-2-propanol, 10-200
      ng/mL for 2,3-dichloro-2-propanol and 10-400 ng/mL for 3-chloropropane-1,2-diol
      with the determination coefficients between 0.9989 and 0.9997. The limits of
      detection were in the range of 0.3-3.2 ng/mL. The precision varied from 1.9 to
      10% relative standard deviation (n = 9). The recovery of the method was between
      91 and 101%. Advantages such as low consumption of organic solvents and short
      time of analysis make the method suitable for the biomonitoring of
      chloropropanols. 

PMID- 26205355
TI  - Use of Ambulatory Blood Pressure Monitoring for the Screening of Obstructive
      Sleep Apnea.
AB  - Obstructive sleep apnea (OSA) is a frequent and underdiagnosed disease in
      hypertensive individuals who experience cardiovascular events. The aim of this
      study was to define the best model that combined the ambulatory blood pressure
      (BP) monitoring (ABPM), anthropometric, sociodemographic, and biological
      variables to identify moderate to severe OSA. A total of 105 ABPM-confirmed
      hypertensive patients were evaluated using their clinical histories, blood
      analyses, ABPM, and home respiratory polygraphic results. A multivariate logistic
      regression analysis was performed to identify the significant variables. The best
      model included sex, presence of obesity (body mass index >=30 kg/m(2) and
      abdominal obesity), mean daytime BP, mean nocturnal heart rate, and minimal
      diastolic nighttime BP to achieve an area under the curve of 0.804. Based on this
      model, a validated scoring system was developed to identify the patients with an
      apnea-hypopnea index >=15. Therefore, in untreated hypertensive patients who
      snored, ABPM variables might be used to identify patients at risk for OSA. 

PMID- 26205356
TI  - [Tumours and metastases of the spine : cavity/coblation surgery and
      vertebroplasty/kyphoplasty].
AB  - BACKGROUND: Radical surgery for metastases in the spine is in many cases not
      possible, includingthe higher risk of surgery in older patients with co
      morbidities. The aims of treatment are: minimally invasive and maximally
      effective tumour removal, fracture position, stabilization, pain reduction, and
      improved quality of life. The specific features and problems of diagnosis and
      treatment using the cavity/coblation method, , the surgical technique, and the
      results of the treatment of 250 patients with spinal tumours/metastases are
      presented. MATERIALS AND METHODS: Tumour resection is carried out by plasma
      field, via percutaneous trans-/extrapedicular access, followed by kyphoplasty.
      Clinical and radiological follow-up was carried out postoperatively, including
      data on pain reduction and improvement of quality of life. RESULTS: Within 6
      years (March 2008t February 2014) a total of 250 patients, or 812 spines were
      treated. In 59 cases dorsal percutaneous instrumentation and straightening were
      carried out. Minimal blood loss and a very low complication rate were recorded.
      After surgery, significant pain reduction, satisfaction, early mobilization, and
      improvement in quality of life were demonstrated in all patients. Immediate radio
      and chemotherapy could be carried out. In 38 cases cement escaped laterally into
      the intervertebral space, but this had no clinical relevance. 188 patients have
      since died because of tumour manifestations. CONCLUSIONS: The cavity/coblation
      method has been demonstrated to be a safe, minimally invasive procedure, with
      good short- and long-term results and lower complication rates. A comprehensive
      diagnostic, including tumour staging, the correct indication, and prognosis
      estimation, is important.

PMID- 26205357
TI  - [Osteomalacia and vitamin D deficiency].
AB  - BACKGROUND: Vitamin D and calcium deficiency has a higher incidence in the
      orthopedic-trauma surgery patient population than generally supposed. In the long
      term this can result in osteomalacia, a form of altered bone mineralization in
      adults, in which the cartilaginous, non-calcified osteoid does not mature to hard
      bone. AIM: The current value of vitamin D and its importance for bones and other
      body cells are demonstrated. RESULTS: The causes of vitamin D deficiency are
      insufficient sunlight exposure, a lack of vitamin D3 and calcium, malabsorption,
      and rare alterations of VDR signaling and phosphate metabolism. The main symptoms
      are bone pain, fatigue fractures, muscular cramps, muscle pain, and gait
      disorders, with an increased incidence of falls in the elderly. Osteopathies
      induced by pharmaceuticals, tumors, rheumatism or osteoporosis have to be
      considered as the main differential diagnoses. CONCLUSIONS: In addition to the
      recording of symptoms and medical imaging, the diagnosis of osteomalacia should
      be ensured by laboratory parameters. Adequate treatment consists of the high-dose
      intake of vitamin D3 and the replacement of phosphate if deficient. Vitamin D is
      one of the important hormone-like vitamins and is required in all human cells.
      Deficiency of vitamin D has far-reaching consequences not only for bone, but also
      for other organ systems.

PMID- 26205358
TI  - [Osteosarcomatous dedifferentiated chondrosarcoma].
AB  - A secondary peripheral chondrosarcoma (SPC) evolving from an osteochondroma is
      rare, but it has been described several times. The development of an
      osteosarcomatous dedifferentiated chondrosarcoma in a locally recurrent SPC is
      extremely rare. The following case report of a 46-year-old man demonstrates and
      discusses this phenomenon. 

PMID- 26205359
TI  - [Co-management in geriatric traumatology].
AB  - BACKGROUND: Fragility fractures are becoming more common and are leading to
      significantly increased morbidity and mortality rates. METHOD: In order to
      improve the outcome of these patients, they are increasingly being treated from
      the beginning interdisciplinarily and interprofessionally as part of co
      management models. The main contents of these systems are rapid surgical
      stabilization for rapid remobilization, treatment with standardized paths and
      regular communication within the team and a well-functioning discharge
      management. Furthermore, the organization is a key ingredient in secondary
      prevention of geriatric traumatology. CONCLUSION: If this system can be
      implemented as a whole, this will lead to an improvement of the functional
      outcomes for the patient as well as to cost savings.

PMID- 26205360
TI  - [Use of osteoanabolics in fracture nonunion].
AB  - BACKGROUND: The treatment of fracture nonunion (pseudarthrosis) is often lengthy
      and debilitating for the patient. There are operative and conservative therapies
      available. RESEARCH QUESTION: Does the systemic use of osteoanabolic acting
      substances (osteoanabolics) lead to an acceleration of the delayed fracture
      healing and/or strengthening of the fracture? Which types of pseudarthrosis are
      suitable for this treatment option? MATERIALS AND METHODS: A literature review
      was carried out focusing on the systemic anabolic therapy options for the
      treatment of delayed healing of fractures or pseudarthrosis. Additionally, our
      own case studies are presented. RESULTS: Teriparatide and strontium ranelate have
      a positive effect on the healing of fractures in animal studies and in humans.
      There are also case studies on the use of both substances in delayed fracture
      healing or pseudarthrosis. The scientific knowledge regarding teriparatide is
      significantly more comprehensive. However, prospective randomized trials are
      lacking so far. CONCLUSION: The systemic use of anabolics can be a therapeutic
      option, especially for biological reactive pseudarthrosis. However, these are off
      label treatments and contraindications should be especially well heeded. Because
      of the numerous positive results, from the point of view of teriparatide
      treatment, a multicentric, prospective randomized study on the treatment of
      aseptic pseudarthrosis should be initiated.

PMID- 26205361
TI  - Tamibarotene in patients with acute promyelocytic leukaemia relapsing after
      treatment with all-trans retinoic acid and arsenic trioxide.
AB  - Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and
      all-trans retinoic acid (ATRA) is highly effective first-line therapy, although
      approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid
      with activity in APL patients who relapse after chemotherapy and ATRA, but has
      not been studied in relapse after treatment with ATO and ATRA. We report on a
      phase II study of tamibarotene in adult patients with relapsed or refractory APL
      after treatment with ATRA and ATO (n = 14). Participants were treated with
      tamibarotene (6 mg/m(2) /d) during induction and for up to six cycles of
      consolidation. The overall response rate was 64% (n = 9), the rate of complete
      cytogenetic response was 43% (n = 6) and the rate of complete molecular response
      was 21% (n = 3). Relapse was frequent with 7 of 9 responders relapsing after a
      median of 4.6 months (range 1.6-26.8 months). The median event-free survival
      (EFS) was 3.5 months [95% confidence interval (CI) 0-8.6 months] and the median
      overall survival (OS) was 9.5 months (95% CI 5.9-13.1 months). These results
      demonstrate that tamibarotene has activity in relapsed APL after treatment with
      ATO and ATRA and further studies using tamibarotene as initial therapy and in
      combination with ATO are warranted. 

PMID- 26205362
TI  - 'It is a dilemma': perspectives of nurse practitioners on health screening of
      newly arrived migrants.
AB  - BACKGROUND: Screening newly arrived migrants from countries with high burden of
      communicable diseases of public health significance is part of the Swedish
      national strategy against the spread of these diseases. However, little is known
      about its implementation. OBJECTIVE: This study aimed at exploring caregivers'
      experiences in screening newly arrived migrants to generate knowledge that could
      inform policy and clinical practice. DESIGN: Using an interpretive description
      framework, we conducted semistructured interviews between November and December
      2011 in four Swedish counties, with 15 purposively selected nurses with
      experience in screening migrants. Data were analyzed using thematic analysis.
      RESULTS: Participants described a range of challenges including discordant views
      between migrants and the nurses about medical screening, inconsistencies in rules
      and practices, and conflicting policies. Participants indicated that
      sociocultural differences resulted in divergent expectations with migrants
      viewing the participants as agents of migration authorities. They also expressed
      concern over being given a new assignment without training and being expected to
      share responsibilities with staff from other agencies without adequate
      coordination. Finally, they indicated that existing policies can be confusing and
      raise ethical issues. All these were compounded by language barriers, making
      their work environment extremely complex and stressful. CONCLUSIONS: These
      findings illuminate complex challenges that could limit access to, uptake, and
      delivery of health screening and undermine public health goals, and highlight the
      need for a multilevel approach. This entails avoiding the conflation of migration
      with health issues, harmonizing existing policies to make health care services
      more accessible and acceptable to migrants, and facilitating health
      professionals' work in promoting public health, improving interagency
      collaboration and the skills of all staff involved in understanding and
      effectively responding to migrants' needs, and improving migrants' health
      literacy through community outreach interventions.

PMID- 26205363
TI  - Prevalence and risk factors for self-reported non-communicable diseases among
      older Ugandans: a cross-sectional study.
AB  - BACKGROUND: There is limited evidence about the prevalence and risk factors for
      non-communicable diseases (NCDs) among older Ugandans. Therefore, this article is
      aimed at investigating the prevalence of self-reported NCDs and their associated
      risk factors using a nationally representative sample. DESIGN: We conducted a
      secondary analysis of the 2010 Uganda National Household Survey (UNHS) using a
      weighted sample of 2,382 older people. Frequency distributions for descriptive
      statistics and Pearson chi-square tests to identify the association between self
      reported NCDs and selected explanatory variables were done. Finally,
      multivariable complementary log-log regressions to estimate the risk factors for
      self-reported NCDs among older people in Uganda were done. RESULTS: About 2 in 10
      (23%) older persons reported at least one NCD [including hypertension (16%),
      diabetes (3%), and heart disease (9%)]. Among all older people, reporting NCDs
      was higher among those aged 60-69 and 70-79; Muslims; and Pentecostals and
      Seventh Day Adventists (SDAs). In addition, the likelihood of reporting NCDs was
      higher among older persons who depended on remittances and earned wages; owned a
      bicycle; were sick in the last 30 days; were disabled; and were women.
      Conversely, the odds of reporting NCDs were lower for those who were relatives of
      household heads and were poor. CONCLUSIONS: In Uganda, self-reported NCDs were
      associated with advanced age, being a woman, having a disability, ill health in
      the past 30 days, being rich, depended on remittances and earning wages, being
      Muslim, Pentecostal and SDAs, and household headship. The Ministry of Health
      should prevent and manage NCDs by creating awareness in the public and improving
      the supply of essential drugs for these health conditions. Finally, there is a
      need for specialised surveillance studies of older people to monitor the trends
      and patterns of NCDs over time.

PMID- 26205364
TI  - Regional trade and the nutrition transition: opportunities to strengthen NCD
      prevention policy in the Southern African Development Community.
AB  - BACKGROUND: Addressing diet-related non-communicable diseases (NCDs) will require
      a multisectoral policy approach that includes the food supply and trade, but
      implementing effective policies has proved challenging. The Southern African
      Development Community (SADC) has experienced significant trade and economic
      liberalization over the past decade; at the same time, the nutrition transition
      has progressed rapidly in the region. This analysis considers the relationship
      between regional trade liberalization and changes in the food environment
      associated with poor diets and NCDs, with the aim of identifying feasible and
      proactive policy responses to support healthy diets. DESIGN: Changes in trade and
      investment policy for the SADC were documented and compared with time-series
      graphs of import data for soft drinks and snack foods to assess changes in
      imports and source country in relation to trade and investment liberalization.
      Our analysis focuses on regional trade flows. RESULTS: Diets and the burden of
      disease in the SADC have changed since the 1990s in parallel with trade and
      investment liberalization. Imports of soft drinks increased by 76% into SADC
      countries between 1995 and 2010, and processed snack foods by 83%. South Africa
      acts as a regional trade and investment hub; it is the major source of imports
      and investment related to these products into other SADC countries. At the same
      time, imports of processed foods and soft drinks from outside the region -
      largely from Asia and the Middle East - are increasing at a dramatic rate with
      soft drink imports growing by almost 1,200% and processed snack foods by 750%.
      CONCLUSIONS: There is significant intra-regional trade in products associated
      with the nutrition transition; however, growing extra-regional trade means that
      countries face new pressures in implementing strong policies to prevent the
      increasing burden of diet-related NCDs. Implementation of a regional nutrition
      policy framework could complement the SADC's ongoing commitment to regional trade
      policy.

PMID- 26205365
TI  - Trapping of carbolithiation-derived tertiary benzylic alpha-lithio piperidines
      with carbon electrophiles: Controlling the formation of alpha-amino quaternary
      and vicinal stereocenters.
AB  - The interception of carbolithiation-derived tertiary benzylic alpha-lithio
      piperidines with carbon electrophiles, under HMPA-mediated conditions, has led to
      the diastereoselective synthesis of vicinally functionalized piperidines bearing
      alpha-amino quaternary stereocenters. 

PMID- 26205366
TI  - In Vitro Inhibition of Human Placental Glutathione S-Transferase by 3
      Arylcoumarin Derivatives.
AB  - Glutathione S-transferases (EC: 2.5.1.18, GSTs) are phase II detoxification
      enzymes that catalyze the conjugation of various electrophilic compounds to
      glutathione (GSH), thus usually producing less reactive and more water soluble
      compounds. However, there is evidence that elevated expression of GSTs,
      especially GSTP1, is involved in the resistance of tumor cells against
      chemotherapeutic agents. In this study, we synthesized and investigated the
      inhibitory effects of differently substituted 3-arylcoumarin derivatives on human
      placental GST, identified as GSTP1-1, using 1-chloro-2,4-dinitrobenzene as a
      substrate. A known potent inhibitor of GST, ethacrynic acid was used as a
      positive control. Among the tested compounds, 6,7-dihydroxy substituted coumarin
      derivatives exhibited the highest inhibitory activity (IC50 = 13.50-20.83 MUM).
      These results suggest that 6,7-dihydroxy-3-arylcoumarins may represent a new
      promising scaffold to discover potent GST inhibitors.

PMID- 26205367
TI  - The type of e-cigarette affects its usefulness in smoking cessation.

PMID- 26205368
TI  - The copper transporter 1 (CTR1) is required to maintain the stability of copper
      transporter 2 (CTR2).
AB  - Mammalian cells have two influx Cu transporters that form trimers in membranes.
      CTR1 is the high affinity transporter that resides largely in the plasma
      membrane, and CTR2 is the low affinity transporter that is primarily associated
      with vesicular structures inside the cell. The major differences between CTR1 and
      CTR2 are that CTR1 contains a HIS/MET-rich domain N-terminal of the METS that
      participate in the first two stacked rings that form the pore, and a longer C
      terminal tail that includes a Cu binding HIS-CYS-HIS (HCH) motif right at the
      end. It has been reported that CTR1 and CTR2 are physically associated with each
      other in the cell. We used the CRISPR-Cas9 technology to knock out either CTR1 or
      CTR2 in fully malignant HEK293T and OVCAR8 human ovarian cancer cells to
      investigate the interaction of CTR1 and CTR2. We report here that the level of
      CTR2 protein is markedly decreased in CTR1 knockout clones while the CTR2
      transcript level remains unchanged. CTR2 was found to be highly ubiquitinated in
      the CTR1 knock out cells, and inhibition of the proteasome prevented the
      degradation of CTR2 when CTR1 was not present while inhibition of autophagy had
      no effect. Re-expression of CTR1 rescued CTR2 from degradation in the CTR1
      knockout cells. We conclude that CTR1 is essential to maintain the stability of
      CTR2 and that in the absence of CTR1 CTR2 is degraded by the proteasome. This
      reinforces the concept that the functions of CTR1 and CTR2 are inter-dependent
      within the Cu homeostasis system. 

PMID- 26205369
TI  - Electrocardiographic Monitoring in Patients with Epidermolysis Bullosa: A New
      Proposal.
AB  - Epidermolysis bullosa causes serious blistering of the skin even with minor
      trauma. The use of standard electrodes, tapes, and adhesives is restricted in
      these patients because it exposes the skin to stretching and shearing forces that
      cause traumatic blister formation. We propose herein an alternative
      electrocardiographic monitoring technique to minimize cutaneous trauma. 

PMID- 26205370
TI  - Stenting for chronic obstructive venous disease: A current comprehensive meta
      analysis and systematic review.
AB  - OBJECTIVES: The aim of this article was to summarize the efficacy and safety of
      venous stents in chronic obstructive venous disease (COVD) including
      postthrombotic syndrome (PTS) and nonthrombotic iliac vein lesions (NIVL).
      METHODS: We searched PubMed for case series (prospective and retrospective) that
      focused on venous stents in the treatment of COVD published between 1st January,
      2000 and 15th July, 2014. Then, we analyzed the perioperative complications,
      subsequent antithrombotic treatment, clinical outcomes, and long-term patency of
      this procedure. RESULTS: Overall, 1987 patients from 14 studies were included in
      our study. The incidence of the 30-day thrombotic events was 2.0% (4.0% in PTS
      vs. 0.8% in NIVL, p = 0.0002). The rates of access site complications and stent
      migration were 1.7% and 1.3%, respectively. The incidence of retroperitoneal
      bleeding and contrast extravasation was 1.8%. Back pain was more common with a
      rate of 62.9%. With stent placement, there was a significant pain and edema
      relief in COVD patients and the clinical-etiology-anatomy-pathophysiology scores
      declined. The rate of ulcer healing was 72.1% (70.3% in PTS vs. 86.9% in NIVL, p
      = 0.0022), and the ulcer recurrence rate was 8.7%. The primary, assisted primary,
      and secondary patency rates were 91.4%, 95.0%, and 97.8%, respectively, at 12
      months and 77.1%, 92.3%, and 94.3%, respectively, at 36 months; however, the
      patency rates in PTS were lower than those in NIVL. CONCLUSIONS: Stents may be a
      relatively effective and safe approach for PTS and NIVL patients because of the
      low incidence of perioperative complications and satisfying long-term patency.
      Some outcomes of stents in NIVL patients may be better than those in PTS
      patients.

PMID- 26205371
TI  - Prevalence of Individuals Experiencing the Effects of Stroke in Canada: Trends
      and Projections.
AB  - BACKGROUND AND PURPOSE: Previous estimates of the number and prevalence of
      individuals experiencing the effects of stroke in Canada are out of date and
      exclude critical population groups. It is essential to have complete data that
      report on stroke disability for monitoring and planning purposes. The objective
      was to provide an updated estimate of the number of individuals experiencing the
      effects of stroke in Canada (and its regions), trending since 2000 and forecasted
      prevalence to 2038. METHODS: The prevalence, trends, and projected number of
      individuals experiencing the effects of stroke were estimated using region
      specific survey data and adjusted to account for children aged <12 years and
      individuals living in homes for the aged. RESULTS: In 2013, we estimate that
      there were 405 000 individuals experiencing the effects of stroke in Canada,
      yielding a prevalence of 1.15%. This value is expected to increase to between 654
      000 and 726 000 by 2038. Trends in stroke data between 2000 and 2012 suggest a
      nonsignificant decrease in stroke prevalence, but a substantial and rising
      increase in the number of individuals experiencing the effects of stroke. Stroke
      prevalence varied considerably between regions. CONCLUSIONS: Previous estimates
      of stroke prevalence have underestimated the true number of individuals
      experiencing the effects of stroke in Canada. Furthermore, the projected
      increases that will result from population growth and demographic changes
      highlight the importance of maintaining up-to-date estimates.

PMID- 26205372
TI  - Letter by van Klei and Dieleman Regarding Article, "Type of Anesthesia and
      Differences in Clinical Outcome After Intra-Arterial Treatment for Ischemic
      Stroke".

PMID- 26205373
TI  - Residual Risk of Stroke and Death in Anticoagulated Patients According to the
      Type of Atrial Fibrillation: AMADEUS Trial.
AB  - BACKGROUND AND PURPOSE: Atrial fibrillation (AF) and heart failure frequently
      coexist and are associated with increased morbidity and mortality. We
      investigated the prognosis of anticoagulated patients with permanent AF and
      nonpermanent AF according to preexisting heart failure in the AMADEUS (Evaluating
      the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial
      Fibrillation) trial. METHODS: The primary outcome was a composite of
      cardiovascular death and stroke or systemic embolism, analyzed using a Cox
      proportional hazards model, adjusted for baseline age, sex, diabetes mellitus,
      hypertension, creatinine, and previous cardiovascular diseases. The median follow
      up was 11.6 months (interquartile range, 6.2-15.2). RESULTS: Nonpermanent AF was
      present in 2072 patients (46% of cohort), of which 339 (16%) had preexisting
      heart failure. A total of 2484 patients had permanent AF (54% of cohort), with a
      higher burden of heart failure including 730 patients (29%; P<0.001). Overall,
      death because of cardiovascular causes occurred in 57 patients and 45 had stroke
      or systemic embolism (1.4/100 person-years for each). Overall, the adjusted
      incidence of the composite outcome was higher in patients with permanent AF than
      in patients with nonpermanent AF. In multivariate analysis, permanency of AF,
      creatinine, prior cerebrovascular events, and previous coronary disease were
      independently associated with the primary outcome. The hazard ratio for permanent
      versus nonpermanent AF was 1.68 (95% confidence interval, 1.08-2.55; P=0.02). The
      presence of heart failure increased the risk of adverse outcomes in a similar way
      in both permanent and nonpermanent AF (interaction P value=0.76). CONCLUSIONS:
      The risk of cardiovascular death, stroke, or systemic embolism is higher in
      anticoagulated patients with permanent AF than in those with nonpermanent AF,
      regardless of preexisting heart failure.

PMID- 26205374
TI  - Long-Term Blood-Brain Barrier Permeability Changes in Binswanger Disease.
AB  - BACKGROUND AND PURPOSE: The blood-brain barrier (BBB) is disrupted in small
      vessel disease patients with lacunes and white matter hyperintensities (WMHs).
      The relationship of WMHs and regional BBB permeability changes has not been
      studied. We hypothesized that BBB disruption occurs in normal appearing WM and
      regions near the WMHs. To test the hypothesis, we repeated BBB permeability
      measurements in patients with extensive WMHs related to Binswanger disease.
      METHODS: We selected a subset of 22 Binswanger disease subjects from a well
      characterized larger prospective vascular cognitive impairment cohort. We used 16
      age-matched controls for comparison. The abnormal WM permeability (WMP) was
      measured twice for several years using dynamic contrast-enhanced magnetic
      resonance imaging. WMP maps were constructed from voxels above a predetermined
      threshold. Scans from first and second visits were coregistered. WM was divided
      into 3 regions: normal appearing WM, WMH ring, and WMH core. The ring was defined
      as 2 mm on each side of the WMH border. WMP was calculated in each of the 3
      specific regions. We used paired t test, ANOVA, and Fisher exact test to compare
      individual changes. RESULTS: WMP was significantly higher in subjects than in
      controls (P<0.001). There was no correlation between WMH load and WMP. High
      permeability regions had minimal overlap between first and second scans. Nine
      percent of WMP was within the WMHs, 49% within the normal appearing WM, and 52%
      within the WMH ring (P<0.001; ANOVA). CONCLUSIONS: Increased BBB permeability in
      normal appearing WM and close to the WMH borders supports a relationship between
      BBB disruption and the development of WMHs.

PMID- 26205375
TI  - Letter by Campbell and Short Regarding Article, "Type of Anesthesia and
      Differences in Clinical Outcome After Intra-Arterial Treatment for Ischemic
      Stroke".

PMID- 26205376
TI  - Response to Letter Regarding Article, "Type of Anesthesia and Differences in
      Clinical Outcome After Intra-Arterial Treatment for Ischemic Stroke".

PMID- 26205377
TI  - Long-term efficacy of subtotal splenectomy due to portal hypertension in
      cirrhotic patients.
AB  - BACKGROUND: Portal hypertension (PHT) requires invasive measures to prevent
      rupture and bleeding of esophagogastric varices; however, the long-term results
      of subtotal splenectomy plus fixation of the retrosternal omentum majus (SSFROM)
      have not been reported. Specifically, the advantages and disadvantages of surgery
      that preserves the spleen and the long-term hematologic effects have not been
      described. STUDY DESIGN: Our studies relating to SSFROM commenced in February
      1999. As of April 2014 we have performed 256 subtotal splenectomies The records
      of 65 patients with PHT who underwent SSFROM were reviewed retrospectively.
      RESULTS: Four patients died within 4 years of surgery, with a 4-year survival
      rate of 94 %; the 11-year survival rate was 60 %. Eleven patients (17 %) had re
      bleeding from esophagogastric varices. The white blood cell and platelet counts
      were higher 6 and 11 years post-operatively compared with pre-operative values (P
      < 0.01). Portal venous diameter, portal venous flow volume, splenic artery flow
      volume, as well as splenic length, thickness, and average cross-sectional areas
      were shown to be significantly constricted or decreased (P < 0.01). The
      proportion of serum CD3+ T cells, CD4+ T cells, and CD8+ T cells was increased (P
      < 0.01), while the serum levels of macrophage colony-stimulating factor and
      granulocyte-macrophage colony-stimulating factor were significantly decreased (P
      < 0.01). There was no significant change in the serum levels of IgA, IgM, IgG,
      and Tuftsin (P > 0.05). DSA demonstrated that 15 cases formed collateral
      circulations between the portal vein and superior vena cava. CONCLUSION: SSFROM
      provide long-term hemostasis for esophagogastric variceal bleeding in PHT and
      corrected hypersplenism. SSFROM is an effective treatment for patients with PHT
      in whom long-term survival is expected.

PMID- 26205378
TI  - A Small-Molecule Probe for Selective Profiling and Imaging of Monoamine Oxidase B
      Activities in Models of Parkinson's Disease.
AB  - The design of the first dual-purpose activity-based probe of monoamine oxidase B
      (MAO-B) is reported. This probe is highly selective towards MAO-B, even at high
      MAO-A expression levels, and could sensitively report endogenous MAO-B activities
      by both in situ proteome profiling and live-cell bioimaging. With a built-in
      imaging module as part of the probe design, the probe was able to accomplish what
      all previously reported MAO-B imaging probes failed to do thus far: the live-cell
      imaging of MAO-B activities without encountering diffusion problems.

PMID- 26205379
TI  - A cross sectional comparison of postnatal care quality in facilities
      participating in a maternal health voucher program versus non-voucher facilities
      in Kenya.
AB  - BACKGROUND: Health service fees constitute substantial barriers for women seeking
      childbirth and postnatal care. In an effort to reduce health inequities, the
      government of Kenya in 2006 introduced the output-based approach (OBA), or
      voucher programme, to increase poor women's access to quality Safe Motherhood
      services including postnatal care. To help improve service quality, OBA
      programmes purchase services on behalf of the poor and marginalised, with
      provider reimbursements for verified services. Kenya's programme accredited
      health facilities in three districts as well as in two informal Nairobi
      settlements. METHODS: Postnatal care quality in voucher health facilities (n =
      21) accredited in 2006 and in similar non-voucher health facilities (n = 20) are
      compared with cross sectional data collected in 2010. Summary scores for quality
      were calculated as additive sums of specific aspects of each attribute
      (structure, process, outcome). Measures of effect were assessed in a linear
      regression model accounting for clustering at facility level. Data were analysed
      using Stata 11.0. RESULTS: The overall quality of postnatal care is poor in
      voucher and non-voucher facilities, but many facilities demonstrated 'readiness'
      for postnatal care (structural attributes: infrastructure, equipment, supplies,
      staffing, training) indicated by high scores (83/111), with public voucher
      facilities scoring higher than public non-voucher facilities. The two groups of
      facilities evinced no significant differences in postnatal care mean process
      scores: 14.2/55 in voucher facilities versus 16.4/55 in non-voucher facilities;
      coefficient: -1.70 (-4.9, 1.5), p = 0.294. Significantly more newborns were seen
      within 48 hours (83.5% versus 72.1%: p = 0.001) and received Bacillus Calmette
      Guerin (BCG) (82.5% versus 76.5%: p < 0.001) at voucher facilities than at non
      voucher facilities. CONCLUSIONS: Four years after facility accreditation in
      Kenya, scores for postnatal care quality are low in all facilities, even those
      with Safe Motherhood vouchers. We recommend the Kenya OBA programme review its
      Safe Motherhood reimbursement package and draw lessons from supply side results
      based financing initiatives, to improve postnatal care quality.

PMID- 26205380
TI  - Analysis of EPR and FISH studies of radiation doses in persons who lived in the
      upper reaches of the Techa River.
AB  - Waterborne radioactive releases into the Techa River from the Mayak Production
      Association in Russia during 1949-1956 resulted in significant doses to about
      30,000 persons who lived in downstream settlements. The residents were exposed to
      internal and external radiation. Two methods for reconstruction of the external
      dose are considered in this paper, electron paramagnetic resonance (EPR)
      measurements of teeth, and fluorescence in situ hybridization (FISH) measurements
      of chromosome translocations in circulating lymphocytes. The main issue in the
      application of the EPR and FISH methods for reconstruction of the external dose
      for the Techa Riverside residents was strontium radioisotopes incorporated in
      teeth and bones that act as a source of confounding local exposures. In order to
      estimate and subtract doses from incorporated (89,90)Sr, the EPR and FISH assays
      were supported by measurements of (90)Sr-body burdens and estimates of (90)Sr
      concentrations in dental tissues by the luminescence method. The resulting dose
      estimates derived from EPR to FISH measurements for residents of the upper Techa
      River were found to be consistent: The mean values vary from 510 to 550 mGy for
      the villages located close to the site of radioactive release to 130-160 mGy for
      the more distant villages. The upper bound of individual estimates for both
      methods is equal to 2.2-2.3 Gy. The EPR- and FISH-based dose estimates were
      compared with the doses calculated for the donors using the most recent Techa
      River Dosimetry System (TRDS). The TRDS external dose assessments are based on
      the data on contamination of the Techa River floodplain, simulation of air kerma
      above the contaminated soil, age-dependent lifestyles and individual residence
      histories. For correct comparison, TRDS-based doses were calculated from two
      sources: external exposure from the contaminated environment and internal
      exposure from (137)Cs incorporated in donors' soft tissues. It is shown here that
      the TRDS-based absorbed doses in tooth enamel and muscle are in agreement with
      EPR- and FISH-based estimates within uncertainty bounds. Basically, this
      agreement between the estimates has confirmed the validity of external doses
      calculated with the TRDS.

PMID- 26205382
TI  - A 15-year randomized controlled study of a reduced shrinkage stress resin
      composite.
AB  - OBJECTIVES: The aim of this randomized controlled study was to evaluate the long
      term effectiveness of a reduced shrinkage stress resin composite in Class II
      restorations. The material was compared intra-individually with a microhybrid
      resin composite. MATERIALS AND METHODS: Each of 50 patients with at least one
      pair of two similar sized Class II cavities participated (22 female, 28 male,
      mean age 43 years, range 18-64). Each participant received in each pair, in a
      randomized way, one Class II restoration performed with a reduced shrinkage
      stress resin composite (InTen-S) and the other restoration with a microhybrid
      resin composite restoration (Point 4). Both restorations were placed with an etch
      and-rinse bonding system and an oblique layering technique. A total of 106
      restorations, 33 premolar and 73 molars, were placed. The restorations were
      evaluated blindly each year using modified USPHS criteria. The overall
      performance of the experimental restorations was tested after intra-individual
      comparison using the Friedmans two-way analysis of variance test. The hypothesis
      was rejected at the 5% level. RESULTS: At 15 years, 91 restorations were
      evaluated. The drop out frequency was 15 restorations (5 male, 3 female
      participants; 2 premolar and 13 molar restorations). Except for 2 participants,
      who reported slight symptoms during a few weeks after placement, no post
      operative sensitivity was observed at the recalls. The overall success rate at 15
      years was 77%. Twenty-one non acceptable restorations were observed during the 15
      years follow up, 10 InTen-S (21.7%) and 11 Point 4 (24.4%) restorations (p>0.05).
      Annual failure rates for the resin composites were 1.5% and 1.6%, respectively.
      The main reasons for failure were secondary caries (8) and resin composite
      fracture (7). The differences between premolar vs. molar restorations and between
      restorations in male vs. female participants were not significant. Significant
      differences were observed between 2-surface vs. 3-surface restorations.
      SIGNIFICANCE: During the 15-year follow up, the reduced shrinkage stress resin
      composite showed a good clinical durability in Class II cavities, but not
      significantly better than the control microhybrid resin composite. Secondary
      caries and material fracture were the main reasons of failure.

PMID- 26205381
TI  - Bone augmentation using a new injectable bone graft substitute by combining
      calcium phosphate and bisphosphonate as composite--an animal model.
AB  - OBJECTIVE: The aim of this study was to create a new injectable bone graft
      substitute by combining the features of calcium phosphate and bisphosphonate as a
      composite bone graft to support bone healing and to evaluate the effect of
      alendronate to the bone healing process in an animal model. MATERIAL AND METHOD:
      In this study, 24 New Zealand white rabbits were randomly divided into two
      groups: a calcium phosphate alendronate group and a calcium phosphate control
      group. A defect was created at the proximal medial tibia and filled with the new
      created injectable bone graft substitute calcium phosphate alendronate or with
      calcium phosphate. Healing process was documented by fluoroscopy. To evaluate the
      potential of the bone graft substitute, the proximal tibia was harvested 2, 4,
      and 12 weeks after operation. Histomorphological analysis was focused on the
      evaluation of the dynamic bone parameters using the Osteomeasure system. RESULTS:
      Radiologically, the bone graft materials were equally absorbed. No fracture was
      documented. The bones healed normally. After 2 weeks, the histological analysis
      showed an increased new bone formation for both materials. The osteoid volume per
      bone volume (OV/BV) was significantly higher for the calcium phosphate group.
      After 4 weeks, the results were almost equal. The trabecular thickness (Tb.Th)
      increased in comparison to week 2 in both groups with a slight advantage for the
      calcium phosphate group. The total mass of the bone graft (KEM.Ar) and the bone
      graft substitute surface density (KEM.Pm) were consistently decreasing. After 12
      weeks, the new bone volume per tissue volume (BV/TV) was still constantly
      growing. Both bone grafts show a good integration. New bone was formed on the
      surface of both bone grafts. The calcium phosphate as well as the calcium
      phosphate alendronate paste had been enclosed by the bone. The trabecular
      thickness was higher in both groups compared to the first time point. CONCLUSION:
      Calcium phosphate proved its good potential as a bone graft substitute.
      Initially, the diagrams seem to show a tendency that alendronate improves the
      known properties of calcium phosphate as a bone graft substitute. The composite
      graft induced a good and constant new bone formation. Not only the graft was
      incorporated into the bone but also a new bone was formed on its surface. But we
      could not prove a significant difference between the grafts. Both implants proved
      their function as a bone graft substitute, but the bisphosphonate alendronate
      does not support the bone healing process sufficiently that the known properties
      of calcium phosphate as a bone graft substitute were improved in the sense of a
      composite graft. In this study, alendronate used as a bone graft in a healthy
      bony environment did not influence the bone healing process in a positive or
      negative way.

PMID- 26205383
TI  - Porosity distribution in root canals filled with gutta percha and calcium
      silicate cement.
AB  - OBJECTIVE: Gutta percha is commonly used in conjunction with a sealer to produce
      a fluid-tight seal within the root canal fillings. One of the most commonly used
      filling methods is lateral compaction of gutta percha coupled with a sealer such
      as calcium silicate cement. However, this technique may result in voids and
      worse, the filling procedures may damage the root. METHODS: We compared the
      volume of the voids associated with two root canal filling methods, namely
      lateral compaction and single cone. Micro-computed tomography was used to assess
      the porosity associated with each method in vitro. An automated, observer
      independent analysis protocol was used to quantify the unfilled regions and the
      porosity located in the sealer surrounding the gutta percha. RESULTS:
      Significantly less porosity was observed in root canals filled with the single
      cone technique (0.445% versus 3.095%, p<0.001). Porosity near the crown of the
      tooth was reduced 6 fold, whereas in the mid root region porosity was reduced to
      less than 10% of values found in the lateral compaction filled teeth.
      SIGNIFICANCE: Our findings suggest that changing the method used to place the
      endodontic biomaterials improves the quality and homogeneity of root canal
      fillings.

PMID- 26205390
TI  - The complete chloroplast genome sequence of Morus mongolica and a comparative
      analysis within the Fabidae clade.
AB  - The complete nucleotide sequence of the Morus mongolica chloroplast (cp) genome
      was reported and characterized in this study. The cp genome is a circular
      molecule of 158,459 bp containing a pair of 25,678 bp IR regions, separated by
      small and large single-copy regions of 19,736 and 87,363 bp, respectively. The
      number and relative positions of the 114 unique genes (80 PCGs, 30 tRNAs, and 4
      rRNA genes) are almost identical to Morus indica cp genome. Further detailed
      comparative analyses revealed one hypervariable region, which is responsible for
      88% of the total variation, and 64 indel events between two individuals. There
      are 78 simple sequence repeats (SSRs) in M. mongolica cp genome, in which 58 of
      them are mononucleotide repeats. Comparative analysis with M. indica cp genome
      indicated 22 SSRs with length polymorphisms and 1 SSR with nucleotide content
      polymorphism. The phylogenetic analysis of 60 PCGs from 62 cp genomes provided
      strong support for the monophyletic, single origin of Fabidae (N2-fixing) clade.

PMID- 26205391
TI  - Phylodynamic analysis of the canine distemper virus hemagglutinin gene.
AB  - BACKGROUND: Canine distemper (CD) is one of the most contagious and lethal viral
      diseases in dogs. Despite the widespread use of vaccines, the prevalence of the
      CD virus (CDV) has increased at an alarming rate in recent years. In this
      phylodynamic study, we investigated the spatiotemporal modes of dispersal, viral
      demographic trends, and effectiveness of vaccines for CDV. A total of 188 full
      length CDV hemagglutinin (H) gene sequences dataset were subjected to
      recombination analysis, including seven from modified live vaccine (MLV) strains
      and 12 from Taiwan specimens. After excluding the MLV strains and potential
      recombinant strains, alignments of 176 of 188 previous CDV strains were further
      used to analyze phylodynamic characteristics, and evidence of selection, and co
      evolution. RESULTS: The CDV genotype consisted of MLV-associated genotypes such
      as America-1 and Rockborn-like strains, which were characterized by long terminal
      branches and no distinct geographical patterns among lineages. In contrast, wild
      type isolates clustered into lineages with a spatiotemporal structure and short
      terminal branches. Co-circulation and extensive diversification were
      simultaneously observed. The sequence variation signature was shaped by both
      geographic diversity and host tropism. Codon 506 was identified as a multi
      epistatic interacting in the H protein. CONCLUSIONS: The topological signature
      revealed in this study suggests different epidemic scenarios. For example, a
      ladder-like backbone is a hallmark of directional selection, and cladogenesis at
      long terminal branches indicates the emergence of a surviving lineage. The stable
      effective viral population of CDV indicate the effectiveness of vaccines
      currently used to control the virus.

PMID- 26205392
TI  - Applications of the NTID speech recognition test (NSRT((r))).
AB  - OBJECTIVE: This study evaluated the diagnostic capabilities of an adaptive speech
      recognition protocol (NSRT((r))) that can be self-administered in non-clinical
      venues by listeners using internet-based software. DESIGN: All participants were
      given an audiological evaluation, including pure-tone testing, and responded to
      the NSRT administered in quiet and + 5 dB SNR listening conditions. The NSRT test
      materials are sentence-length utterances containing phonetic contrasts, primarily
      minimal pairs. STUDY SAMPLE: Subjects were 123 adults with normal hearing to
      moderately severe sensorineural hearing loss (mean age = 55 years, SD = 23).
      RESULTS: Performance on the NSRT is strongly related to pure-tone thresholds.
      Linear regression analyses support the utility of the NSRT as a proxy for
      clinically-obtained hearing thresholds across the octave frequencies 0.5 to 8
      kHz, primarily for individuals in the - 10 to 55 dB HL range. Other NSRT results
      are linked to analyses of phonetic errors and components of aural rehabilitation.
      CONCLUSIONS: Among its numerous results, the NSRT yields quantitative predictions
      of frequency-specific hearing thresholds, provides insight into the phonetic
      errors that affect speech understanding in adults who suffer from sensorineural
      hearing loss, primarily in the - 10 to 55 dB HL range, and has implications for
      the design of individualized auditory training programs.

PMID- 26205393
TI  - Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 26205394
TI  - Journey to a faraway land.

PMID- 26205395
TI  - Objective tumor response to denosumab in patients with giant cell tumor of bone:
      a multicenter phase II trial.
AB  - BACKGROUND: Giant cell tumor of bone (GCTB) is a rare primary bone tumor,
      characterized by osteoclast-like giant cells that express receptor activator of
      nuclear factor-kappa B (RANK), and stromal cells that express RANK ligand
      (RANKL), a key mediator of osteoclast activation. A RANKL-specific inhibitor,
      denosumab, was predicted to reduce osteolysis and control disease progression in
      patients with GCTB. PATIENTS AND METHODS: Seventeen patients with GCTB were
      enrolled. Patients were treated with denosumab at 120 mg every 4 weeks, with a
      loading dose of 120 mg on days 8 and 15. To evaluate efficacy, objective tumor
      response was evaluated prospectively by an independent imaging facility on the
      basis of prespecified criteria. RESULTS: The proportion of patients with an
      objective tumor response was 88% based on best response using any tumor response
      criteria. The proportion of patients with an objective tumor response using
      individual response criteria was 35% based on the modified Response Evaluation
      Criteria in Solid Tumors (RECIST) criteria, 82% based on the modified European
      Organization for Research and Treatment of Cancer (EORTC) criteria, and 71% based
      on inverse Choi criteria. The median time of study treatment was 13.1 months.
      CONCLUSION: The findings demonstrate that denosumab has robust clinical efficacy
      in the treatment of GCTB.

PMID- 26205396
TI  - A case of mantle cell lymphoma presenting as IgG4-related dacryoadenitis and
      sialoadenitis, so-called Mikulicz's disease.
AB  - BACKGROUND: Mantle cell lymphoma (MCL) is a relatively uncommon type of non
      Hodgkin lymphoma. It develops in the outer edge of a lymph node called the mantle
      zone. In contrast, IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) is
      characterized by elevated serum IgG4 and persistent bilateral enlargement of
      lacrimal glands (LGs) and salivary glands (SGs), with infiltration of IgG4
      positive plasma cells. Recent studies indicated the importance of differentiation
      between IgG4-DS and malignant lymphoma. CASE PRESENTATION: An 82-year-old man was
      suspected of IgG4-DS because of a high serum IgG level (2174 mg/dL) and bilateral
      swelling of LGs and SGs. Lip biopsy and fine needle biopsy of submandibular gland
      were performed, and subsequently, MCL was diagnosed through the histopathological
      findings. CONCLUSIONS: MCL most commonly occurs in the Waldeyer ring, but rarely
      in the stomach, spleen, skin, LG, and SG. We report an unusual case of MCL
      involving LGs and SGs mimicking IgG4-DS, which suggests that IgG4 testing may be
      useful in the differentiation of IgG4-DS in the presence of bilateral swelling of
      LGs or SGs.

PMID- 26205398
TI  - Determination of the impurities in drug products containing montelukast and in
      silico/in vitro genotoxicological assessments of sulfoxide impurity.
AB  - Impurities affecting safety, efficacy, and quality of pharmaceuticals are of
      increasing concern for regulatory agencies and pharmaceutical industries, since
      genotoxic impurities are understood to play important role in carcinogenesis. The
      study aimed to analyse impurities of montelukast chronically used in asthma
      theraphy and perform genotoxicological assessment considering regulatory
      approaches. Impurities (sulfoxide, cis-isomer, Michael adducts-I&II,
      methylketone, methylstyrene) were quantified using RP-HPLC analysis on commercial
      products available in Turkish market. For sulfoxide impurity, having no toxicity
      data and found to be above the qualification limit, in silico mutagenicity
      prediction analysis, miniaturized bacterial gene mutation test, mitotic index
      determination and in vitro chromosomal aberration test w/wo metabolic activation
      system were conducted. In the analysis of different batches of 20 commercial drug
      products from 11 companies, only sulfoxide impurity exceeded qualification limit
      in pediatric tablets from 2 companies and in adult tablets from 7 companies.
      Leadscope and ToxTree programs predicted sulfoxide impurity as nonmutagenic. It
      was also found to be nonmutagenic in Ames MPF Penta I assay. Sulfoxide impurity
      was dose-dependent cytotoxic in human peripheral lymphocytes, however, it was
      found to be nongenotoxic. It was concluded that sulfoxide impurity should be
      considered as nonmutagenic and can be classified as ordinary impurity according
      to guidelines. 

PMID- 26205399
TI  - Clinical trials in melanoma patients with brain metastases.

PMID- 26205400
TI  - Geographic clustering of emergency department presentations for atrial
      fibrillation and flutter in Alberta, Canada.
AB  - OBJECTIVES: Atrial fibrillation and flutter (AFF) are the most common arrhythmias
      seen in the outpatient setting, and they affect more than 300,000 adult
      Canadians. The aims of this study were to examine temporal and geographic trends
      in emergency department (ED) presentations made by adults (age >= 35 years) for
      AFF in Alberta, Canada, from 1999 to 2011. Statistical disease cluster detection
      techniques were used to identify geographic areas with higher numbers of
      individuals presenting with AFF and higher numbers of ED presentations for AFF
      than expected by chance alone. Geographic clusters of individuals with stroke or
      heart failure follow-up within 365 days of ED presentations for AFF were also
      identified. METHODS: All ED presentations for AFF made by individuals aged >=35
      years were extracted from Alberta's Ambulatory Care Classification System. The
      Alberta Health Care Insurance Plan provided population counts and demographics
      for the patients presenting (age, sex, year, geographic unit). The Physician
      Claims File provided non-ED physician claims data after a patient's ED
      presentation. Statistical analyses included numerical and graphical summaries,
      directly standardized rates, and statistical disease cluster detection tests.
      RESULTS: During 12 years, there were 63,395 ED presentations for AFF made by
      32,101 individuals. Standardized rates remained relatively stable over time, at
      about two per 1,000 for individuals presenting to the ED for AFF and about three
      per 1,000 for ED presentations for AFF. The northern and southeastern parts of
      the province were identified as clusters of individuals presenting for AFF, and
      ED presentations for AFF, and several of the areas demonstrated clusters in
      multiple years. Further, several of the geographic clusters were also identified
      as potential clusters for stroke or heart failure within 365 days after the ED
      presentations for AFF. CONCLUSIONS: This population-based study spanned 12 fiscal
      years and showed variations in the number of people presenting to EDs for AFF and
      the number of ED presentations for AFF over geography. The potential clusters
      identified may represent geographic areas with higher disease severity or a lower
      availability of non-ED health services. The clusters are not all likely to have
      occurred by chance, and further investigation and intervention could occur to
      reduce ED presentations for AFF.

PMID- 26205401
TI  - Building Resilience and Organizational Readiness During Healthcare Facility
      Redevelopment Transitions: Is It Possible to Thrive?
AB  - OBJECTIVE: Hospital redevelopment constitutes a revolutionary change that can
      face strong resistance from employees. Few studies have examined how employee
      readiness for change relates to adjustment outcomes typically captured in post
      occupancy evaluation (POE). The relationship between organizational readiness and
      employee adjustment is examined in the context of a POE conducted during a
      hospital redevelopment. BACKGROUND: Our study focuses on the redevelopment of a
      complex continuing care and rehabilitation hospital that underwent complete
      physical redevelopment and major shifts in operational and organizational
      processes. METHODS: Using a pretest-posttest quasi-experimental research design,
      staff organizational readiness was assessed using surveys at four time periods: 6
      months prior to the move (n = 125), 2 months prior to the move (n = 84), 3 months
      after the move (n = 187), and 6 months after the move (n = 194). Measures
      included organizational readiness, workplace satisfaction, psychological factors
      (well-being and optimism), and sociodemographic information. RESULTS: Findings
      suggest readiness changes from pre- to post-move, with notable drops just prior
      (2 months) and just post (3 months) hospital move. Employees demonstrated
      significant increases in workplace satisfaction and interprofessional
      relationships from 6 months prior to the move to 6 months after. Results suggest
      that higher readiness is related to improved employee adjustment. CONCLUSIONS: A
      supportive change environment was found to encourage positive employee outcomes
      in the face of revolutionary change. It is recommended that change management
      activities be tailored not only to employee need but also to the timing of the
      change process.

PMID- 26205402
TI  - Trichuris suis induces human non-classical patrolling monocytes via the mannose
      receptor and PKC: implications for multiple sclerosis.
AB  - INTRODUCTION: The inverse correlation between prevalence of auto-immune disorders
      like the chronic neuro-inflammatory disease multiple sclerosis (MS) and the
      occurrence of helminth (worm) infections, suggests that the helminth-trained
      immune system is protective against auto-immunity. As monocytes are regarded as
      crucial players in the pathogenesis of auto-immune diseases, we explored the
      hypothesis that these innate effector cells are prime targets for helminths to
      exert their immunomodulatory effects. RESULTS: Here we show that soluble products
      of the porcine nematode Trichuris suis (TsSP) are potent in changing the
      phenotype and function of human monocytes by skewing classical monocytes into
      anti-inflammatory patrolling cells, which exhibit reduced trans-endothelial
      migration capacity in an in vitro model of the blood-brain barrier.
      Mechanistically, we identified the mannose receptor as the TsSP-interacting
      monocyte receptor and we revealed that specific downstream signalling occurs via
      protein kinase C (PKC), and in particular PKCdelta. CONCLUSION: This study
      provides comprehensive mechanistic insight into helminth-induced
      immunomodulation, which can be therapeutically exploited to combat various auto
      immune disorders.

PMID- 26205404
TI  - Preclinical Testing Oncolytic Vaccinia Virus Strain GLV-5b451 Expressing an Anti
      VEGF Single-Chain Antibody for Canine Cancer Therapy.
AB  - Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a novel
      approach for canine cancer therapy. Here we describe, for the first time, the
      characterization and the use of VACV strain GLV-5b451 expressing the anti
      vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as
      therapeutic agent against different canine cancers. Cell culture data
      demonstrated that GLV-5b451 efficiently infected and destroyed all four tested
      canine cancer cell lines including: mammary carcinoma (MTH52c), mammary adenoma
      (ZMTH3), prostate carcinoma (CT1258), and soft tissue sarcoma (STSA-1). The GLV
      5b451 virus-mediated production of GLAF-2 antibody was observed in all four
      cancer cell lines. In addition, this antibody specifically recognized canine
      VEGF. Finally, in canine soft tissue sarcoma (CSTS) xenografted mice, a single
      systemic administration of GLV-5b451 was found to be safe and led to anti-tumor
      effects resulting in the significant reduction and substantial long-term
      inhibition of tumor growth. A CD31-based immuno-staining showed significantly
      decreased neo-angiogenesis in GLV-5b451-treated tumors compared to the controls.
      In summary, these findings indicate that GLV-5b451 has potential for use as a
      therapeutic agent in the treatment of CSTS. 

PMID- 26205403
TI  - The Emerging Role of miRNAs in HTLV-1 Infection and ATLL Pathogenesis.
AB  - Human T-cell leukemia virus (HTLV)-1 is a human retrovirus and the etiological
      agent of adult T-cell leukemia/lymphoma (ATLL), a fatal malignancy of CD4/CD25+ T
      lymphocytes. In recent years, cellular as well as virus-encoded microRNA (miRNA)
      have been shown to deregulate signaling pathways to favor virus life cycle. HTLV
      1 does not encode miRNA, but several studies have demonstrated that cellular
      miRNA expression is affected in infected cells. Distinct mechanisms such as
      transcriptional, epigenetic or interference with miRNA processing machinery have
      been involved. This article reviews the current knowledge of the role of cellular
      microRNAs in virus infection, replication, immune escape and pathogenesis of HTLV
      1. 

PMID- 26205406
TI  - Pigeon RIG-I Function in Innate Immunity against H9N2 IAV and IBDV.
AB  - Retinoic acid-inducible gene I (RIG-I), a cytosolic pattern recognition receptor
      (PRR), can sense various RNA viruses, including the avian influenza virus (AIV)
      and infectious bursal disease virus (IBDV), and trigger the innate immune
      response. Previous studies have shown that mammalian RIG-I (human and mice) and
      waterfowl RIG-I (ducks and geese) are essential for type I interferon (IFN)
      synthesis during AIV infection. Like ducks, pigeons are also susceptible to
      infection but are ineffective propagators and disseminators of AIVs, i.e., "dead
      end" hosts for AIVs and even highly pathogenic avian influenza (HPAI).
      Consequently, we sought to identify pigeon RIG-I and investigate its roles in the
      detection of A/Chicken/Shandong/ZB/2007 (H9N2) (ZB07), Gansu/Tianshui (IBDV TS)
      and Beijing/CJ/1980 (IBDV CJ-801) strains in chicken DF-1 fibroblasts or human
      293T cells. Pigeon mRNA encoding the putative pigeon RIG-I analogs was
      identified. The exogenous expression of enhanced green fluorescence protein
      (EGFP)-tagged pigeon RIG-I and caspase activation and recruitment domains
      (CARDs), strongly induced antiviral gene (IFN-beta, Mx, and PKR) mRNA synthesis,
      decreased viral gene (M gene and VP2) mRNA expression, and reduced the viral
      titers of ZB07 and IBDV TS/CJ-801 virus strains in chicken DF-1 cells, but not in
      293T cells. We also compared the antiviral abilities of RIG-I proteins from
      waterfowl (duck and goose) and pigeon. Our data indicated that waterfowl RIG-I
      are more effective in the induction of antiviral genes and the repression of ZB07
      and IBDV TS/CJ-801 strain replication than pigeon RIG-I. Furthermore, chicken
      melanoma differentiation associated gene 5(MDA5)/ mitochondrial antiviral
      signaling (MAVS) silencing combined with RIG-I transfection suggested that pigeon
      RIG-I can restore the antiviral response in MDA5-silenced DF-1 cells but not in
      MAVS-silenced DF-1 cells. In conclusion, these results demonstrated that pigeon
      RIG-I and CARDs have a strong antiviral ability against AIV H9N2 and IBDV in
      chicken DF-1 cells but not in human 293T cells. 

PMID- 26205405
TI  - Exosomes: Implications in HIV-1 Pathogenesis.
AB  - Exosomes are membranous nanovesicles of endocytic origin that carry host and
      pathogen derived genomic, proteomic, and lipid cargos. Exosomes are secreted by
      most cell types into the extracellular milieu and are subsequently internalized
      by recipient cells. Upon internalization, exosomes condition recipient cells by
      donating their cargos and/or activating various signal transduction pathways,
      consequently regulating physiological and pathophysiological processes. The role
      of exosomes in viral pathogenesis, especially human immunodeficiency virus type 1
      [HIV-1] is beginning to unravel. Recent research reports suggest that exosomes
      from various sources play important but different roles in the pathogenesis of
      HIV-1. From these reports, it appears that the source of exosomes is the defining
      factor for the exosomal effect on HIV-1. In this review, we will describe how HIV
      1 infection is modulated by exosomes and in turn how exosomes are targeted by HIV
      1 factors. Finally, we will discuss potentially emerging therapeutic options
      based on exosomal cargos that may have promise in preventing HIV-1 transmission. 

PMID- 26205407
TI  - Phylogenetic Studies of the Three RNA Silencing Suppressor Genes of South
      American CTV Isolates Reveal the Circulation of a Novel Genetic Lineage.
AB  - Citrus Tristeza Virus (CTV) is the most economically important virus of citrus
      worldwide. Genetic diversity and population structure of CTV isolates from all
      citrus growing areas from Uruguay were analyzed by RT-PCR and cloning of the
      three RNA silencing suppressor genes (p25, p20 and p23). Bayesian phylogenetic
      analysis revealed the circulation of three known genotypes (VT, T3, T36) in the
      country, and the presence of a new genetic lineage composed by isolates from
      around the world, mainly from South America. Nucleotide and amino acid identity
      values for this new genetic lineage were both higher than 97% for the three
      analyzed regions. Due to incongruent phylogenetic relationships, recombination
      analysis was performed using Genetic Algorithms for Recombination Detection
      (GARD) and SimPlot software. Recombination events between previously described
      CTV isolates were detected. High intra-sample variation was found, confirming the
      co-existence of different genotypes into the same plant. This is the first report
      describing: (1) the genetic diversity of Uruguayan CTV isolates circulating in
      the country and (2) the circulation of a novel CTV genetic lineage, highly
      present in the South American region. This information may provide assistance to
      develop an effective cross-protection program. 

PMID- 26205408
TI  - Structure-activity relationship studies on quinoxalin-2(1H)-one derivatives
      containing thiazol-2-amine against hepatitis C virus leading to the discovery of
      BH6870.
AB  - Chronic hepatitis C virus infection represents a serious global public health
      problem, typically resulting in fibrosis, cirrhosis, and ultimately
      hepatocellular carcinoma. Based on our previous discovery of lead compound 2 (Liu
      et al. J Med Chem 54:5747-5768, 2011), 35 new quinoxalinone derivatives were
      explored in this study. Outline of the structure-activity relationships (SARs)
      revealed that compound BH6870 (36) showed high anti-HCV potency ([Formula: see
      text]) and a good cell safety index (SI [Formula: see text]). SARs analysis
      indicated that quinoxalin-2(1H)-one containing a 4-aryl-substituted thiazol-2
      amine moiety was optimal for antiviral activity. Introducing a hydrogen-bond
      acceptor (such as ester or amide group) at the C-3 position of quinoxalin-2(1H)
      one was beneficial for the antiviral potency, and especially, N,N-disubstituted
      amide was far superior to N-monosubstituted amide. Incorporation of more than one
      halogen (fluorine or chlorine atom) or a strong electron-withdrawing group on the
      benzene ring of the thiazole-phenyl moiety might reduce electron atmosphere
      density further and resulted in a dramatical loss of activity. The NH-group of
      the lactam moiety was clearly required for anti-HCV activity. Design and
      synthesis of quinoxalin-2(1H)-one derivatives as new non-nucleoside small
      molecule HCV inhibitors. BH6870 (36), showing higher antiviral potency and a good
      cell safety index, was identified. 

PMID- 26205409
TI  - Topological sub-structural molecular design (TOPS-MODE): a useful tool to explore
      key fragments of human A3 adenosine receptor ligands.
AB  - Adenosine regulates tissue function by activating four G-protein-coupled
      adenosine receptors (ARs). Selective agonists and antagonists for A3 ARs have
      been investigated for the treatment of a variety of immune disorders, cancer,
      brain, and heart ischemic conditions. We herein present a QSAR study based on a
      Topological sub-structural molecular design (TOPS-MODE) approach, intended to
      predict the A3 ARs of a diverse dataset of 124 (94 training set/ 30 prediction
      set) adenosine derivatives. The final model showed good fit and predictive
      capability, displaying 85.1 % of the experimental variance. The TOPS-MODE
      approach afforded a better understanding and interpretation of the developed
      model based on the useful information extracted from the analysis of the
      contribution of different molecular fragments to the affinity.

PMID- 26205411
TI  - Landcare GIS: Evaluating Land Management Programs in Australia.
AB  - Land degradation in Australia is a persistent national problem. Australian
      governments, in partnership with community groups, are addressing land
      degradation through initiatives such as the Decade of Landcare Plan and the
      National Landcare Program (NLP). The NLP has funded over 3500 projects, through
      various sub-programs since the start of the Decade of Landcare in 1990. The
      Commonwealth Government is currently evaluating these programs as Australia
      enters the middle of the decade. To assist this evaluation, the Bureau of
      Resource Sciences has developed a spatial information system - LANDCARE GIS - to
      provide an integrated analytical approach. LANDCARE GIS has been used to identify
      and analyse the spatial relationships between the NLP, land resource condition
      and land use practices. It presently contains five main categories of data
      including: details of projects; national and State surveys of land condition;
      State surveys of landcare groups; surveys of landcare and land management
      practices; and other resource, biophysical and socio-economic data. LANDCARE GIS
      is one of the first examples of spatial information technology developed for the
      evaluation of Australian Government programs and policies. It is able to provide
      information on the effectiveness of programs and on the strategic allocation of
      resources within priority areas. A preliminary assessment of landcare activities
      is described, including (i) descriptions of NLP activities, (ii) the extent to
      which the NLP is targeting land degradation problems, (iii) a comparison of
      landcare and non-landcare farmer management practices, and (iv) an analysis of
      farmers' perceptions of land degradation. Many Australian Government departments
      are now adding geographic information systems (GIS) to their management 'tool
      kits'. 

PMID- 26205410
TI  - Experimental host preference of diapause and non-diapause induced Culex pipiens
      pipiens (Diptera: Culicidae).
AB  - BACKGROUND: Culex pipiens pipiens plays an important role in the transmission of
      several vector-borne pathogens such as West Nile virus (WNV) in North America.
      Laboratory and field studies suggest that this species is ornithophilic but
      because of genetic hybridization with sibling species during the active mosquito
      season, it may occasionally feed on mammals. Adult female Cx. p. pipiens undergo
      a facultative diapause and may serve as an overwintering mechanism for WNV. To
      determine the effect of diapause on the innate host preference of Cx. p. pipiens
      emerging from winter hibernation, we conducted host-choice experiments using bird
      and mammal hosts. METHODS: Mosquitoes were reared under non-diapause induced
      (NDI), diapause induced (DI), and field collected from overwintering (OW)
      hibernaculae. They were released into a large mesh enclosure housing two lard can
      traps, and given a choice between feeding on a dove or a rat. RESULTS: Host
      seeking Cx. p. pipiens were four times more likely to feed on the dove than the
      rat, regardless of experimental conditions. Under NDI conditions, Cx. p. pipiens
      were (p < 0.001) more attracted to the bird (79.9% [75.6-84.1]) than the rat
      (20.1 [15.9-24.4]). Overwintering mosquitoes and those exposed to DI conditions
      were also significantly (p < 0.001) more attracted to birds (81.6% [75.9-87.3])
      than to rats (18.5 [12.7-24.2]). CONCLUSIONS: We provide new information about
      the innate host preference of Cx. p. pipiens emerging from diapause in temperate
      habitats where winter survival is crucial for disease transmission cycles.
      Although we showed that Cx. p. pipiens prefers an avian to a mammalian host,
      nearly 20% of emerging mosquitoes in the spring could feed on mammals. Changes in
      host preferences may also contain valuable clues about transmission dynamics and
      subsequent timely interventions by vector control and public health
      practitioners.

PMID- 26205412
TI  - Monitoring of the Phytosanitary State of Navarra's Forests, Spain.
AB  - Between 1988 and 1993 six surveys on the condition of forests in Navarra (North
      Spain) were carried out. The results, relating to 408 trees in 17 sampling
      points, showed that the overall percentage of damaged trees increased from 2.86%
      in 1988 to 18.6% in 1993, which indicates a general large-scale deterioration of
      forest condition. Among the most common groups of trees, the most severely
      affected species were Quercus faginea, Quercus robur and Pinus sylvestris.
      Furthermore, it was observed that defoliation and discoloration processes did not
      occur randomly between stand trees, but the trees that were damaged one year
      (1992) were more predisposed to suffer damage in the next year (1993). 

PMID- 26205413
TI  - Metal and Trace Element Burdens in Two Shorebird Species at Two Sympatric
      Wintering Sites in Southern California.
AB  - In January and November, 1994, ten willets (Catoptrophorus semipalmatus) and ten
      black-bellied plovers (Pluvialis squatarola) were collected at a south-facing
      sandy beach at the North Island Naval Air Station (NASNI) and ten willets and
      three plovers were collected at the Tijuana Slough National Wildlife Refuge
      (TSNWR), 16 km to the southeast. Concentrations of 19 inorganic analytes were
      determined in the livers. Differences between sexes in diet or abilities to
      retain some analytes are indicated because male willets tend to have greater
      levels of Cd than females and male plovers tend to have greater levels of Fe, Hg,
      and Mn than females. Concentrations of Hg and Mg in willets decreased from
      January to November. If this decrease is a part of an annual cycle, then the
      birds may be acquiring those elements while at NASNI. The differences between
      sites shows higher levels of As and Se but lower levels of Mn in willets at NASNI
      while plovers have lower levels of Cu, Mg and Zn at NASNI. There were no
      correlations between Hg and Se concentrations in the livers of any sample group
      of birds. 

PMID- 26205414
TI  - Metal Accumulation by Riverine and Lacustrine Populations of Angulyagra Oxytropis
      (Benson) (Gastropoda : Viviparidae).
AB  - Cadmium, chromium, iron, manganese, nickel, lead and zinc concentrations were
      determined in sediment and body tissues, viz. digestive gland, mantle and shell,
      of the freshwater snail, Angulyagra oxytropis (Benson) (Gastropoda :
      Viviparidae), from River Barak and one of its floodplain lakes in Cachar
      district, Assam State, Northeastern India. The concentrations of all the metals
      except iron are significantly higher in the lake sediment. When compared to their
      riverine counterparts, the lacustrine snails contain higher concentrations of
      cadmium, chromium and iron in their mantle; nickel and zinc in digestive gland;
      manganese in both digestive gland and mantle; and lead in all the three tissues
      examined. The accumulation patterns of most of the metals varied considerably
      between the two sites. The implications of these findings in storage,
      sequestration and detoxification of metals by this animal are discussed. The
      study also indicates that A. oxytropis may be a potential biological indicator of
      metal contamination in freshwater ecosystems. 

PMID- 26205415
TI  - Evaluation of Phytoplankton Community Indices for Detecting Eutrophic Trends in
      the Marine Environment.
AB  - Twenty two diversity, evenness and dominance indices based on phytoplankton
      community structure were examined for their sensitivity to assess eutrophic
      conditions. Data from two sampling sites, one eutrophic and one oligotrophic,
      were used as reference data-sets for evaluating the indices. McNaughton's
      dominance index, cell number, species number (Hill's N0), Kothe's species
      deficit, Odum's species per thousand individuals and Evenness E2, E3 seemed to be
      the most sensitive indices for discriminating between eutrophic and oligotrophic
      conditions. A case study was also performed using a data-set from ten stations
      spaced along the coastal area of the city of Rhodes, Aegean Sea, Greece to find
      out which of the indices were appropriate to assess different levels of
      eutrophication. Kothe's species deficit, Hill's N0 (species number), Margalef's
      and Gleason's indices have shown the highest sensitivity to resolve oligotrophic,
      mesotrophic and eutrophic conditions. 

PMID- 26205416
TI  - Groundwater Monitoring Strategies for Variable Versus Constant Contaminant
      Loading Functions.
AB  - Contaminant plumes were derived for constant and variable loading functions at
      locations within a landfill. Annually, the alternative loading functions injected
      the same volume of contaminated water. Mass transport modeling was used to
      evaluate the detection efficiencies of 25 monitoring transects, spaced evenly
      between the landfill and a downgradient compliance boundary. Respectively, the
      most efficient transects (requiring the fewest monitoring wells) for constant and
      variable loading were located at 60-64 and 40 percent of the distance to the
      compliance boundary. The mean detection efficiency was 29 percent higher for
      variable loading, but the variation in detection efficiency was similar for
      constant and variable loading. At the most efficient transects, the minimum
      number of detection wells was 20 percent lower for variable loading. Given the
      influence of source loading on monitoring efficiency, alternative loading
      functions should be considered when designing detection monitoring networks in
      aquifers. 

PMID- 26205417
TI  - Background Levels of Metals in Soils, McMurdo Station, Antarctica.
AB  - McMurdo Station is the largest research station in Antarctica, with a population
      that ranges each year from 250 to 1200 people. Because of its size and 40-year
      history of use, a number of locations around the station have become contaminated
      with wastes. Soils and sediments in these areas have been shown to contain
      elevated levels of petroleum-related products, PCBs, other organics, and metals.
      While some remedial investigations have been conducted, background levels of
      metals in soils have not been determined. This paper reports on background levels
      of metals in a natural basalt-derived soil ('gray soil') and scoria (soft porous
      rock used as fill, 'red soil') near McMurdo Station using two fundamentally
      different analytical procedures, concentrated acid extraction/analysis and total
      metals. These data facilitate determining the extent and levels of metal
      contamination near McMurdo Station and provide reference levels of metals for
      comparison with existing and future remediation data. There were statistically
      significant differences between metals concentrations in both gray and red soils,
      and no correlations between the level of extracted versus total metal. Generally,
      only a small fraction of a metal was extractable. 

PMID- 26205418
TI  - Measuring outcomes for neurophysiological intraoperative monitoring.

PMID- 26205419
TI  - Highly sensitive, label-free and real-time detection of alpha-fetoprotein using a
      silicon nanowire biosensor.
AB  - Alpha-fetoprotein (AFP) is a tumor-associated fetal protein that can be expressed
      in large amounts in adult tumor cells, serving as a useful clinical tumor-marker.
      Silicon nanowire (SiNW) biosensors have emerged as a powerful tool in detecting
      protein biomarkers, due to their ultrahigh sensitivity, real-time response and
      label-free detection. We fabricated a SiNW-based field-effect transistor (FET)
      according to "top-down" methodology. First, anti-AFP antibodies were immobilized
      onto the surface of the SiNW-FET. A polydimethylsiloxane (PDMS) microchannel was
      then integrated to the modified SiNW-FET. Various concentrations of AFP were then
      pumped through the sensing area. We observed a current change that corresponded
      to binding of AFP onto the surface of our anti-AFP functionalized SiNW-FET
      biosensor. Concentrations of AFP as low as 0.1 ng/mL were detected. The results
      implicate our SiNW biosensor as an effective AFP biomarker detector with
      promising potential in clinical applications. 

PMID- 26205420
TI  - Structures of DegQ from Legionella pneumophila Define Distinct ON and OFF States.
AB  - HtrA (high-temperature requirement A) family proteins play important roles in
      protein-quality control processes in the bacterial periplasm. A common feature of
      all members of this family is their modular organization comprising a
      chymotrypsin-like protease domain and at least one PDZ (postsynaptic density of
      95 kDa, disks large homolog 1 and zonula occludens 1) domain. All characterized
      HtrA proteins assemble into complex oligomers consisting of typically 3-24
      monomers, which allow a tight regulation of proteolytic activity. Here, we
      provide evidence that the assembly of proteolytically active, higher-order
      complexes of DegQ from Legionella pneumophila is triggered by the binding of
      substrate-derived peptides. Crystal structures of inactive 3-mers and active 12
      mers of DegQ reveal molecular details of elements of a conserved allosteric
      activation cascade that defines distinct protease ON and OFF states. Results from
      DegQ(Lp) variants harboring structure-based amino acid substitutions indicate
      that peptide binding to the PDZ1 domain is critical for proteolytic activity but
      not for the formation of higher-order oligomers. Combining structural,
      mutagenesis and biochemical data, we show that, in contrast to the proteolytic
      activity, the chaperone function of DegQ is not affected by the state of the
      activation cascade.

PMID- 26205421
TI  - CASP11 refinement experiments with ROSETTA.
AB  - We report new Rosetta-based approaches to tackling the major issues that confound
      protein structure refinement, and the testing of these approaches in the CASP11
      experiment. Automated refinement protocols were developed that integrate a range
      of sampling methods using parallel computation and multiobjective optimization.
      In CASP11, we used a more aggressive large-scale structure rebuilding approach
      for poor starting models, and a less aggressive local rebuilding plus core
      refinement approach for starting models likely to be closer to the native
      structure. The more incorrectly modeled a structure was predicted to be, the more
      it was allowed to vary during refinement. The CASP11 experiment revealed
      strengths and weaknesses of the approaches: the high-resolution strategy
      incorporating local rebuilding with core refinement consistently improved
      starting structures, while the low-resolution strategy incorporating the
      reconstruction of large parts of the structures improved starting models in some
      cases but often considerably worsened them, largely because of model selection
      issues. Overall, the results suggest the high-resolution refinement protocol is a
      promising method orthogonal to other approaches, while the low-resolution
      refinement method clearly requires further development. Proteins 2016; 84(Suppl
      1):314-322. (c) 2015 Wiley Periodicals, Inc.

PMID- 26205422
TI  - Characterization of the Nencki Affective Picture System by discrete emotional
      categories (NAPS BE).
AB  - The Nencki Affective Picture System (NAPS; Marchewka, Zurawski, Jednorog, &
      Grabowska, Behavior Research Methods, 2014) is a standardized set of 1,356
      realistic, high-quality photographs divided into five categories (people, faces,
      animals, objects, and landscapes). NAPS has been primarily standardized along the
      affective dimensions of valence, arousal, and approach-avoidance, yet the
      characteristics of discrete emotions expressed by the images have not been
      investigated thus far. The aim of the present study was to collect normative
      ratings according to categorical models of emotions. A subset of 510 images from
      the original NAPS set was selected in order to proportionally cover the whole
      dimensional affective space. Among these, using three available classification
      methods, we identified images eliciting distinguishable discrete emotions. We
      introduce the basic-emotion normative ratings for the Nencki Affective Picture
      System (NAPS BE), which will allow researchers to control and manipulate stimulus
      properties specifically for their experimental questions of interest. The NAPS BE
      system is freely accessible to the scientific community for noncommercial use as
      supplementary materials to this article.

PMID- 26205423
TI  - Mechanism of potassium ion uptake by the Na(+)/K(+)-ATPase.
AB  - The Na(+)/K(+)-ATPase restores sodium (Na(+)) and potassium (K(+))
      electrochemical gradients dissipated by action potentials and ion-coupled
      transport processes. As ions are transported, they become transiently trapped
      between intracellular and extracellular gates. Once the external gate opens,
      three Na(+) ions are released, followed by the binding and occlusion of two K(+)
      ions. While the mechanisms of Na(+) release have been well characterized by the
      study of transient Na(+) currents, smaller and faster transient currents mediated
      by external K(+) have been more difficult to study. Here we show that external
      K(+) ions travelling to their binding sites sense only a small fraction of the
      electric field as they rapidly and simultaneously become occluded. Consistent
      with these results, molecular dynamics simulations of a pump model show a wide
      water-filled access channel connecting the binding site to the external solution.
      These results suggest a mechanism of K(+) gating different from that of Na(+)
      occlusion. 

PMID- 26205424
TI  - A high frequency of viral agents yet absence of Borrelia burgdorferi is seen
      within the myocardium of subjects with normal left ventricular systolic function:
      an electron microscopy study.
AB  - A wide range of viral agents is associated with the development of acute
      myocarditis and its possible chronic sequela, dilated cardiomyopathy (DCM). There
      is also increasing evidence that Borrelia burgdorferi (Bb) is associated with DCM
      in endemic regions for Bb infection. This study sought to use electron microscopy
      to prospectively analyze the presence of viruses and Bb within the myocardium of
      40 subjects with preserved left ventricular (LV) ejection fraction and 40
      patients with new-onset unexplained DCM during the same time period. Virus
      particles were found within the myocardium of 23 subjects (58%) of both cohorts
      studied, yet there was no statistically significant difference in virus family
      presence between those with DCM versus those with preserved LV systolic function.
      In contrast, Bb was detected only in those subjects with DCM (0 versus 5
      subjects; p ? 0.05). Polymerase chain reaction was performed on samples from
      patients who were positive for Bb according to electron microscopy, and Bb was
      confirmed in 4 out of 5 individuals. Our results demonstrate that the prevalence
      of viral particles does not differ between subjects with preserved LV systolic
      function versus those with DCM and therefore suggests that the mere presence of a
      viral agent within the myocardium is not sufficient to establish a clear link
      with the development of DCM. In contrast, the presence of Bb was found only
      within myocardial samples of patients with DCM; this finding supports the idea of
      a causal relationship between Bb infection and DCM development.

PMID- 26205425
TI  - Exploring methodological frameworks for a mental task-based near-infrared
      spectroscopy brain-computer interface.
AB  - BACKGROUND: Near-infrared spectroscopy (NIRS) brain-computer interfaces (BCIs)
      enable users to interact with their environment using only cognitive activities.
      This paper presents the results of a comparison of four methodological frameworks
      used to select a pair of tasks to control a binary NIRS-BCI; specifically, three
      novel personalized task paradigms and the state-of-the-art prescribed task
      framework were explored. NEW METHODS: Three types of personalized task selection
      approaches were compared, including: user-selected mental tasks using weighted
      slope scores (WS-scores), user-selected mental tasks using pair-wise accuracy
      rankings (PWAR), and researcher-selected mental tasks using PWAR. These
      paradigms, along with the state-of-the-art prescribed mental task framework,
      where mental tasks are selected based on the most commonly used tasks in
      literature, were tested by ten able-bodied participants who took part in five
      NIRS-BCI sessions. RESULTS: The frameworks were compared in terms of their
      accuracy, perceived ease-of-use, computational time, user preference, and length
      of training. Most notably, researcher-selected personalized tasks resulted in
      significantly higher accuracies, while user-selected personalized tasks resulted
      in significantly higher perceived ease-of-use. It was also concluded that PWAR
      minimized the amount of data that needed to be collected; while, WS-scores
      maximized user satisfaction and minimized computational time. COMPARISON WITH
      EXISTING METHOD: In comparison to the state-of-the-art prescribed mental tasks,
      our findings show that overall, personalized tasks appear to be superior to
      prescribed tasks with respect to accuracy and perceived ease-of-use. CONCLUSIONS:
      The deployment of personalized rather than prescribed mental tasks ought to be
      considered and further investigated in future NIRS-BCI studies.

PMID- 26205426
TI  - Impact of cognitive stimulation on ripples within human epileptic and non
      epileptic hippocampus.
AB  - BACKGROUND: Until now there has been no way of distinguishing between
      physiological and epileptic hippocampal ripples in intracranial recordings. In
      the present study we addressed this by investigating the effect of cognitive
      stimulation on interictal high frequency oscillations in the ripple range (80-250
      Hz) within epileptic (EH) and non-epileptic hippocampus (NH). METHODS: We
      analyzed depth EEG recordings in 10 patients with intractable epilepsy, in whom
      hippocampal activity was recorded initially during quiet wakefulness and
      subsequently during a simple cognitive task. Using automated detection of ripples
      based on amplitude of the power envelope, we analyzed ripple rate (RR) in the
      cognitive and resting period, within EH and NH. RESULTS: Compared to quiet
      wakefulness we observed a significant reduction of RR during cognitive
      stimulation in EH, while it remained statistically marginal in NH. Further, we
      investigated the direct impact of cognitive stimuli on ripples (i.e. immediately
      post-stimulus), which showed a transient statistically significant suppression of
      ripples in the first second after stimuli onset in NH only. CONCLUSION: Our
      results point to a differential reactivity of ripples within EH and NH to
      cognitive stimulation.

PMID- 26205427
TI  - What is the relationship between gestational age and docosahexaenoic acid (DHA)
      and arachidonic acid (ARA) levels?
AB  - Long chain polyunsaturated fatty acids (LCPUFA) including docosahexaenoic acid
      (DHA) and arachidonic acid (ARA) are increasingly transferred from mother to
      fetus late in pregnancy. Infants born before this transfer is complete are at
      risk for deficiency. This study determines the relationship between gestational
      age (GA) and circulating LCPUFA levels to better understand the unique needs of
      premature infants born at various GAs. Whole blood was collected within the first
      7 days of life from 60 preterm (<=34 weeks GA) and 30 term infants (>=38 weeks
      GA) and FA levels were analyzed. Since concurrent intravenous lipid emulsion can
      skew composition data, blood LCPUFA concentrations were also measured. Levels
      were compared among groups, and linear regression models were used to examine the
      association between FA composition and GA. Preterm infants had significantly
      lower DHA and ARA levels than term peers, and whether assessed as concentrations
      or compositions, both directly correlated with GA (p<0.0001). Moreover, FA
      comparisons suggest that premature infants have impaired synthesis of LCPUFAs
      from precursors and may require preformed DHA and ARA. This study confirms that
      essential FA status is strongly related to GA, and that those babies born the
      earliest are at the greatest risk of LCPUFA deficiency. 

PMID- 26205428
TI  - A silver nanoparticle loaded TiO2 nanoporous layer for visible light induced
      antimicrobial applications.
AB  - A nanoporous TiO2 layer was formed on commercially pure titanium by a simple
      anodization method in aqueous hydrofluoric acid (HF) medium. Silver nanoparticles
      (AgNP) were loaded into the nanoporous TiO2 layer by UV light irradiation. The
      morphology, chemical composition and photocatalytic activity of the modified
      titanium surfaces were characterized by scanning electron microscopy, Raman
      spectroscopy, X-ray photoelectron spectroscopy and UV-vis absorption spectroscopy
      techniques. The redox behavior of the AgNP loaded TiO2 layer was analyzed by
      cyclic voltammetry (CV) studies. The impedance behavior of the nanoporous TiO2
      layer with and without AgNP was investigated by electrochemical impedance
      spectroscopy (EIS). The antibacterial effect of the AgNP loaded TiO2 layer was
      evaluated using Pseudomonas sp. and Bacillus sp. cultures. The efficacy of this
      modified layer to act as an antibacterial agent to minimize biofouling of
      titanium is demonstrated in this investigation. 

PMID- 26205429
TI  - Combination of congenital left atrial appendage aneurysm in an infant with
      transposition of the great arteries: a previously unreported association.
AB  - A 35-day-old boy weighing 4.5 kg was referred to our department from a general
      paediatric hospital due to low oxygen saturation. His transcutaneous oxygen
      saturation was 75%. Transthoracic echocardiography showed discordant ventriculo
      arterial connections, a non-restrictive atrial septal defect, and patent ductus
      arteriosus, in addition to a 23 mm*10-mm left atrial appendage aneurysm. As far
      as we know, this association has not been reported previously in the literature. 

PMID- 26205430
TI  - New platinum and ruthenium Schiff base complexes for water splitting reactions.
AB  - New platinum(ii) and ruthenium(ii) mononuclear complexes with naphthalene-based
      Schiff base ligands L1 (H2-selnaph) and L2 (H2-selnaph-COOH) were synthesized: Pt
      selnaph (), Pt-selnaph-COOH (), Ru-selnaph(4-picoline)2 (), and Ru
      selnaph(isoquinoline)2 (). The complexes were characterized by NMR spectroscopy,
      matrix-assisted laser desorption/ionization time-of-flight spectrometry, and
      elemental analysis, and their electrochemical and photophysical properties were
      investigated. The luminescent complexes and were used as photosensitizers for
      visible-light driven hydrogen production reactions in the presence of sacrificial
      electron donor triethylamine and cocatalyst precursor K2PtCl4 aqueous solution.
      When complex was attached to the surface of TiO2 by a carboxyl group, enhanced
      hydrogen photogeneration was achieved compared with complex alone, with turnover
      numbers of about 84 after 12 h irradiation. Calculations based on electrochemical
      and spectroscopic data also confirmed the feasibility of electron injection
      through the carboxyl group of complex into the conduction band of TiO2 for
      hydrogen production reactions. Complexes and were found to be efficient stable
      water oxidation (NH4)2Ce(NO3)6-driven catalysts with a first-order reaction
      behavior. A turnover frequency of 5.34 min(-1) was achieved for complex , while
      complex exhibited an enhanced turnover frequency of 11.9 min(-1) in pH 1.0
      aqueous solution. Turnover numbers up to 1400 and 2060 were obtained after 6.5 h
      of reaction for and , respectively. Unique mechanistic information for water
      splitting is also presented through electrochemical, spectroscopic and ESI-MS
      high-valent ruthenium-oxo intermediate investigations. 

PMID- 26205431
TI  - Improving Disparity Research by Imputing Missing Data in Health Care Records.

PMID- 26205432
TI  - Bilateral atrial appendage thrombus formation in a patient with atrial
      fibrillation.

PMID- 26205433
TI  - Coenzyme Q10 and Pyridoxal Phosphate Deficiency Is a Common Feature in
      Mucopolysaccharidosis Type III.
AB  - Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by
      deficiencies of lysosomal enzymes catalyzing degradation of glycosaminoglycans
      (GAGs). Previously, we reported a secondary plasma coenzyme Q10 (CoQ) deficiency
      in MPS patients. For this study, nine MPS patients were recruited in the Hospital
      Sant Joan de Deu (HSJD, Barcelona) and two patients in the Neurometabolic Unit,
      National Hospital (NMU, London), to explore the nutritional status of MPS type
      III patients by analyzing several vitamins and micronutrients in blood and in
      cerebrospinal fluid. Plasma CoQ and plasma and cerebrospinal fluid pyridoxal
      phosphate (PLP) content were analyzed by high-pressure liquid chromatography
      (HPLC) with electrochemical and fluorescence detection, respectively. We found
      that most MPS-III patients disclosed low plasma pyridoxal phosphate (PLP) values
      (seven out of nine) and also low plasma CoQ concentrations (eight out of nine).
      We observed significantly lower median values of PLP, tocopherol, and CoQ (Mann
      Whitney U test, p = 0.006, p = 0.004, and p = 0.001, respectively) in MPS
      patients when compared with age-matched controls. Chi-square test showed a
      significant association between the fact of having low plasma PLP and CoQ values
      in the whole cohort of patients. Cerebrospinal fluid PLP values were clearly
      deficient in the two patients studied. In conclusion, we report a combined CoQ
      and PLP deficiency in MPS-III patients. These observations could be related to
      the complexity of the physiopathology of the disease. If our results are
      confirmed in larger series of patients, CoQ and PLP therapy could be trialed as
      coadjuvant therapy with the current MPS treatments.

PMID- 26205434
TI  - Speech Pathology Reliability for Stroke Swallowing Screening Items.
AB  - Swallowing screening is critical in rapid identification of risk of aspiration in
      patients presenting with acute stroke symptoms. Accuracy in judgments is vital
      for the success of the screening. This study examined speech-language
      pathologists' (SLPs) reliability in interpreting screening items. Swallowing
      screening was completed in 75 individuals admitted with stroke symptoms.
      Screening items evaluated were lethargy, dysarthria, wet voice unrelated to
      swallowing, abnormal volitional cough, and cough, throat clear, wet voice after
      swallowing, and inability to continuously drink with ingestion of 5 and 90 ml
      water. Two SLPs, each with more than 10 years of experience, made simultaneous
      independent judgments of the same observations obtained from the screening.
      Overall, generally high agreement was identified between the SLPs (k[SE] =
      0.83[0.03]). Individual kappas ranged from 0.38 (fair) for non-swallowing wet
      voice to 0.95 (almost perfect) for cough after swallow, with one item omitted due
      to minimal variation. SLPs demonstrate high reliability in swallowing screening.
      Results, however, indicate some potential variability. Items associated with
      trial swallows had the highest reliability, whereas items related to judgments of
      speech and voice quality had the lowest. Although SLPs have dedicated training
      and ample opportunity to practice, differences in agreement are evident. Routine
      practice in hospital departments is recommended to establish and maintain
      sensitive perceptual discrimination. If other professionals are to provide
      swallowing screening, knowledge of SLPs' reliability levels must be considered
      when identifying screening items, creating education modules, and determining
      acceptable levels of agreement.

PMID- 26205435
TI  - Swallowing Tablets and Capsules Increases the Risk of Penetration and Aspiration
      in Patients with Stroke-Induced Dysphagia.
AB  - We evaluated the prevalence of difficulties swallowing solid dosage forms in
      patients with stroke-induced dysphagia and whether swallowing tablets/capsules
      increases their risk of penetration and aspiration. Concurrently, we explored
      whether routinely performed assessment tests help identify patients at risk.
      Using video endoscopy, we evaluated how 52 patients swallowed four different
      placebos (round, oval, and oblong tablets and a capsule) with texture-modified
      water (TMW, pudding consistency) and milk and rated their swallowing performance
      according to the Penetration Aspiration Scale (PAS). Additionally, Daniels Test,
      Bogenhausener Dysphagiescore, Scandinavian Stroke Scale, Barthel Index, and
      Tinetti's Mobility Test were conducted. A substantial proportion of the patients
      experienced severe difficulties swallowing solid oral dosage forms (TMW: 40.4 %,
      milk: 43.5 %). Compared to the administration of TMW/milk alone, the placebos
      increased the PAS values in the majority of the patients (TMW: median PAS from
      1.5 to 2.0; milk: median PAS from 1.5 to 2.5, each p value <0.0001) and residue
      values were significantly higher (p < 0.05). Whereas video-endoscopic examination
      reliably identified patients with difficulties swallowing medication, neither
      patients' self-evaluation nor one of the routinely performed bedside tests did.
      Therefore, before video-endoscopic evaluation, many drugs were modified
      unnecessarily and 20.8 % of these were crushed inadequately, although switching
      to another dosage form or drug would have been possible. Hence, safety and
      effectiveness of swallowing tablets and capsules should be evaluated routinely in
      video-endoscopic examinations, tablets/capsules should rather be provided with
      TMW than with milk, and the appropriateness of "non per os except medication"
      orders for dysphagic stroke patients should be questioned.

PMID- 26205436
TI  - Esophageal Involvement in Multiple System Atrophy.
AB  - The prevalence of esophageal involvement and its impact on clinical
      manifestations in patients with multiple system atrophy (MSA) remains unknown. We
      recruited 16 consecutive patients with dysphagia associated with MSA (MSA group)
      and 16 consecutive patients with dysphagia associated with amyotrophic lateral
      sclerosis (ALS group). We assessed the presence or absence of food stagnation
      within the esophagus using videofluorography. Food stagnation within the
      esophagus was observed in 16 patients (100 %; 7 severe, 9 mild) in the MSA group
      and in 4 patients (25 %; 4 mild) in the ALS group (P < 0.001). Follow-up
      videofluorography revealed that food stagnation in patients with MSA could
      exacerbate during the disease course. Patients with MSA and severe food
      stagnation showed a wide range of intraesophageal stasis by videofluorography.
      Among the 16 patients in the MSA group, 4 developed aspiration pneumonia and 1
      died of suffocation associated with food regurgitation during continuous positive
      airway pressure therapy. In conclusion, food stagnation within the esophagus
      occurs more frequently in MSA patients with dysphagia than in ALS patients with
      dysphagia. Because food stagnation can cause serious complications such as
      aspiration pneumonia and suffocation, patients with MSA should be evaluated by
      videofluorography, especially those with stagnation in the esophageal phase. 

PMID- 26205437
TI  - Letter to the Editor.

PMID- 26205438
TI  - Impact of a Developmental Care Training Course on the Knowledge and Satisfaction
      of Health Care Professionals in Neonatal Units: A Multicenter Study.
AB  - BACKGROUND: The impact of health-related continuing education courses on
      knowledge acquisition and clinical practice is infrequently evaluated, despite
      higher numbers of people enrolling in them. The majority of health care
      professionals working in neonatal intensive care units (NICUs) have received no
      training in developmental care (DC). The purpose of this study was to determine
      whether participation in a theoretical-practical course on DC had an effect on
      the degree of knowledge possessed by professionals in general terms and with
      respect to neonatal intensive care. The relationship between course satisfaction
      and knowledge acquisition was also studied. METHODS: This was an observational
      multicenter study conducted in 20 neonatal units in Madrid. A pre- and post
      course questionnaire evaluated both knowledge and satisfaction levels regarding
      the course on DC and the Newborn Individualized Developmental Care and Assessment
      Program (NIDCAP). We carried out a multivariate linear regression analysis to
      determine whether there was a correlation between knowledge gained and
      satisfaction level. RESULTS: A total of 566 professionals participated, with a
      99% pre-course and a 90% post-course response rate. The mean rate of correct pre
      course answers was 65%, while the mean rate of post-course correct answers was
      81% (p < 0.001). Results were similar at all levels of neonatal care (Level I:
      64% vs 80%; Level II: 64% vs. 83%; and LEVEL III: 65% vs. 81%). Scores on a scale
      of satisfaction from 1 to 5 were high (averages of above 4 for all lectures and
      workshops). Pre-course knowledge scores, but not satisfaction, significantly
      influenced post-course knowledge (beta 0.499; p < 0.01). CONCLUSION: Previous DC
      knowledge among Madrid health care professionals was similar, regardless of the
      level of neonatal care. Course attendance significantly improved the rate of
      correct answers. Although course satisfaction was high, there did not seem to be
      a correlation between knowledge gained and satisfaction.

PMID- 26205439
TI  - How good is our neonatal BCG uptake? A snapshot in Grampian.
AB  - BACKGROUND: The Neonatal BCG Immunisation programme is a key part of tuberculosis
      (TB) control efforts in the UK; however, there is considerable variability in the
      method of delivery of the programme and monitoring of performance. This study
      aimed to review the extent to which infants at risk of exposure to TB are being
      identified in Grampian and to assess the uptake of BCG vaccination in eligible
      infants. METHODS: The Practitioner Services database and Scottish Immunisation
      Recall System records for all babies born in Grampian in 2012 and 2013 were
      reviewed to identify the number of babies who had a TB risk status recorded and
      to assess the uptake of BCG immunization in at-risk babies. RESULTS: The
      proportion of babies with a risk status recorded was 96.6% in 2012 and 95.5% in
      2013. The uptake of BCG vaccination in at-risk babies was 85.9% in 2012 and 89.9%
      in 2013. CONCLUSIONS: NHS Grampian has an efficient method for identifying
      infants at risk of exposure to TB and has good neonatal BCG vaccination coverage.

PMID- 26205440
TI  - Chinese version of Impact of Weight on Quality of Life for Kids: psychometric
      properties in a large school-based sample.
AB  - BACKGROUND: The Impact of Weight on Quality of Life for Kids (IWQOL-Kids) is the
      first self-report questionnaire for assessing weight-related quality of life for
      youth. However, there is no Chinese version of IWQOL-Kids. Thus, the objective of
      this research was to translate IWQOL-Kids into Mandarin and evaluate its
      psychometric properties in a large school-based sample. METHODS: The total sample
      included 2282 participants aged 11-18 years old, including 1703 non-overweight,
      386 overweight and 193 obese students. IWQOL-Kids was translated and culturally
      adapted by following the international guidelines for instrument linguistic
      validation procedures. The psychometric evaluation included internal consistency,
      test-retest reliability, exploratory factor analysis (EFA), confirmatory factor
      analysis (CFA), convergent validity and discriminant validity. RESULTS:
      Cronbach's alpha for the Chinese version of IWQOL-Kids (IWQOL-Kids-C) was 0.956
      and ranged from 0.891 to 0.927 for subscales. IWQOL-Kids-C showed a test-retest
      coefficient of 0.937 after 2 weeks and ranged from 0.847 to 0.903 for subscales.
      The original four-factor model was reproduced by EFA after seven iterations,
      accounting for 69.28% of the total variance. CFA demonstrated that the four
      factor model had good fit indices with comparative fit index = 0.92, normed fit
      index = 0.91, goodness of fit index = 0.86, root mean square error of
      approximation = 0.07 and root mean square residual = 0.03. Convergent validity
      and discriminant validity were demonstrated with higher correlations between
      similar constructs and lower correlations between dissimilar constructs of IWQOL
      Kids-C and PedsQLTM 4.0. The significant differences were found across the body
      mass index groups, and IWQOL-Kids-C had higher effect sizes than PedsQLTM4.0 when
      comparing non-overweight and obese groups, supporting the sensitivity of IWQOL
      Kids-C. CONCLUSIONS: IWQOL-Kids-C is a satisfactory, valid and reliable
      instrument to assess weight-related quality of life for Chinese children and
      adolescents aged 11-18 years old.

PMID- 26205442
TI  - Selecting the Right Fractional Flow Reserve in an Unsteady State: Keep It Simple.

PMID- 26205441
TI  - Repeatability of Fractional Flow Reserve Despite Variations in Systemic and
      Coronary Hemodynamics.
AB  - OBJECTIVES: This study classified and quantified the variation in fractional flow
      reserve (FFR) due to fluctuations in systemic and coronary hemodynamics during
      intravenous adenosine infusion. BACKGROUND: Although FFR has become a key
      invasive tool to guide treatment, questions remain regarding its repeatability
      and stability during intravenous adenosine infusion because of systemic effects
      that can alter driving pressure and heart rate. METHODS: We reanalyzed data from
      the VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow
      Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY
      Practice) study, which enrolled consecutive patients who were infused with
      intravenous adenosine at 140 MUg/kg/min and measured FFR twice. Raw phasic
      pressure tracings from the aorta (Pa) and distal coronary artery (Pd) were
      transformed into moving averages of Pd/Pa. Visual analysis grouped Pd/Pa curves
      into patterns of similar response. Quantitative analysis of the Pd/Pa curves
      identified the "smart minimum" FFR using a novel algorithm, which was compared
      with human core laboratory analysis. RESULTS: A total of 190 complete pairs came
      from 206 patients after exclusions. Visual analysis revealed 3 Pd/Pa patterns:
      "classic" (sigmoid) in 57%, "humped" (sigmoid with superimposed bumps of varying
      height) in 39%, and "unusual" (no pattern) in 4%. The Pd/Pa pattern repeated
      itself in 67% of patient pairs. Despite variability of Pd/Pa during the hyperemic
      period, the "smart minimum" FFR demonstrated excellent repeatability (bias 
      0.001, SD 0.018, paired p = 0.93, r(2) = 98.2%, coefficient of variation = 2.5%).
      Our algorithm produced FFR values not significantly different from human core
      laboratory analysis (paired p = 0.43 vs. VERIFY; p = 0.34 vs. RESOLVE).
      CONCLUSIONS: Intravenous adenosine produced 3 general patterns of Pd/Pa response,
      with associated variability in aortic and coronary pressure and heart rate during
      the hyperemic period. Nevertheless, FFR - when chosen appropriately - proved to
      be a highly reproducible value. Therefore, operators can confidently select the
      "smart minimum" FFR for patient care. Our results suggest that this selection
      process can be automated, yet comparable to human core laboratory analysis.

PMID- 26205443
TI  - Are We There Yet?: Should All Comatose Cardiac Arrest Survivors Go to the Cath
      Lab?

PMID- 26205444
TI  - Incidence and Potential Mechanism(s) of Post-Procedural Rise of Cardiac Biomarker
      in Patients With Coronary Artery Narrowing After Implantation of an Everolimus
      Eluting Bioresorbable Vascular Scaffold or Everolimus-Eluting Metallic Stent.
AB  - OBJECTIVES: This study sought to evaluate the mechanism of post-procedural
      cardiac biomarker (CB) rise following device implantation. BACKGROUND: A fully
      bioresorbable Absorb scaffold, compared with everolimus-eluting metallic stents
      (EES), might be associated with a higher incidence of periprocedural myocardial
      injury. METHODS: In 501 patients with stable or unstable angina randomized to
      either Absorb (335 patients) or EES (n = 166) in the ABSORB II trial, 3 types of
      CB (creatine kinase, creatine kinase-myocardial band, and troponin) were obtained
      before and after procedure. Per protocol, periprocedural myocardial infarction
      (PMI) was defined as creatine kinase rise >2* the upper limit of normal with
      creatine kinase-myocardial band rise. RESULTS: Incidence of side branch occlusion
      and any anatomic complications assessed by angiography was similar between the 2
      treatment arms (side branch occlusion: Absorb: 5.3% vs. Xience: 7.6%, p = 0.07;
      any anatomic complication: Absorb: 16.4% vs. EES: 19.9%, p = 0.39). Fourteen
      patients who presented with recent myocardial infarction at entry with normalized
      creatine kinase-myocardial band according to the protocol were excluded for post
      CB analysis. The overall compliance for CB was 97.8%. The CB rise subcategorized
      in 7 different ranges was comparable between the 2 treatment arms. PMI rate was
      numerically higher in the Absorb arm according to the per-protocol definitions,
      and treatment with overlapping devices was the only independent determinant of
      per-protocol PMI (odds ratio: 5.07, 95% confidence interval: 1.78 to 14.41, p =
      0.002). CONCLUSIONS: There were no differences in the incidence of CB rise and
      PMI between Absorb and EES. Device overlap might be a precipitating factor of
      myocardial injury. (ABSORB II Randomized Clinical Trial: A Clinical Evaluation to
      Compare the Safety, Efficacy, and Performance of Absorb Everolimus Eluting
      Bioresorbable Vascular Scaffold System Against Xience Everolimus Eluting Coronary
      Stent System in the Treatment of Subjects With Ischemic Heart Disease Caused by
      De Novo Native Coronary Artery Lesions [ABSORB II]; NCT01425281).

PMID- 26205445
TI  - Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the
      Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized
      Observational Study.
AB  - OBJECTIVES: The aim of this study was to assess the safety of the concurrent
      administration of a clopidogrel and prasugrel loading dose in patients undergoing
      primary percutaneous coronary intervention. BACKGROUND: Prasugrel is one of the
      preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial
      infarction patients. The use of prasugrel was evaluated clinically in clopidogrel
      naive patients. METHODS: Between September 2009 and October 2012, a total of
      2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix
      Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS
      (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a
      prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a
      subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary
      safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding
      in hospital at 30 days. RESULTS: Of 2,023 patients undergoing primary
      percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a
      subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose
      alone, and the remaining received clopidogrel only. At 30 days, the primary
      safety endpoint was observed in 1.9% of those receiving clopidogrel and a
      subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading
      dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25
      to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function,
      stroke, bleeding history or predisposition, labile international normalized
      ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher
      in prasugrel-treated patients (p = 0.076). The primary safety endpoint results,
      however, remained unchanged after adjustment for these differences (clopidogrel
      and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI:
      0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death,
      myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95%
      CI: 0.27 to 1.62, p = 0.36). CONCLUSIONS: This observational, nonrandomized study
      of ST-segment elevation myocardial infarction patients suggests that the
      administration of a loading dose of prasugrel in patients pre-treated with a
      loading dose of clopidogrel is not associated with an excess of major bleeding
      events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial
      Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute
      Coronary Syndromes [SPUM-ACS]; NCT01000701).

PMID- 26205446
TI  - Is Transcatheter Aortic Valve Replacement a Durable Therapeutic Strategy?

PMID- 26205447
TI  - What's a Doctor to Do? Balloon, Stents, Drugs, Drills, and Treadmills: Are We
      Closer to the Optimal Algorithm?

PMID- 26205448
TI  - Reply: Coronary Occlusion and Ischemia Reduction.

PMID- 26205449
TI  - Coronary Occlusion and Ischemia Reduction.

PMID- 26205450
TI  - Fate of Bioresorbable Vascular Scaffold Metallic Radio-Opaque Markers at the Site
      of Implantation After Bioresorption.

PMID- 26205451
TI  - 3-Year Follow-Up of the Balloon Elution and Late Loss Optimization Study (BELLO).

PMID- 26205452
TI  - Risk Adjusted Mortality Ratings and Public Reporting for High-Risk PCI.

PMID- 26205453
TI  - Uncertain Detection of Nonuniform Scaffold Expansion Patterns Using Optical
      Coherence Tomography.

PMID- 26205454
TI  - Reply: Triple Antithrombotic Therapy Following Anterior ST-Segment Elevation
      Myocardial Infarction.

PMID- 26205455
TI  - Lost in Translation.

PMID- 26205456
TI  - A Patient With Kawasaki's Disease and Increasing Breathlessness.

PMID- 26205457
TI  - 5-Year Follow-Up After Stenting for Iatrogenic Coronary Stenosis Due to Mitral
      Annuloplasty: Insights With Multiple Imaging Modalities.

PMID- 26205458
TI  - Excimer Laser Angioplasty-Facilitated Fracturing of Napkin-Ring Peri-Stent
      Calcium in a Chronically Underexpanded Stent: Documentation by Optical Coherence
      Tomography.

PMID- 26205459
TI  - Mold elicits atopic dermatitis by reactive oxygen species: Epidemiology and
      mechanism studies.
AB  - Mold has been implicated in the development of atopic dermatitis (AD); however,
      the underlying mechanisms remain unknown. The aim of the study was to investigate
      the effects of mold exposure in early life through epidemiologic and mechanistic
      studies in vivo and in vitro. Exposure to visible mold inside the home during the
      first year of life was associated with an increased risk for current AD by two
      population-based cross-sectional human studies. Children with the AG+GG genotype
      of GSTP1 showed increased risk for current AD when exposed to mold. In the mouse
      model, treatment with patulin induced and aggravated clinically significant AD
      and Th2-related inflammation of the affected mouse skin. Additionally, reactive
      oxygen species (ROS) were released in the mouse skin as well by human
      keratinocytes. In conclusions, mold exposure increases the risk for AD related to
      ROS generation mediated by Th2-promoting inflammatory cytokines. 

PMID- 26205460
TI  - Neurological symptoms in essential thrombocythemia: impact of JAK2V617F mutation
      and response to therapy.
AB  - Patients with essential thrombocythemia (ET) often suffer from neurological
      symptoms (NS) not ever resulting from previous thrombotic cerebral events (TCE).
      We reported NS occurred in 282 patients, in order to identify the factors
      influencing ET-related NS in the absence of TCE, and the response to therapy.
      Overall, 116 of 282 patients (41%) presented NS; 101 of them (87%) reported
      subjective transient and fluctuating NS, without concurrent TCE, which we defined
      as ET-related NS, by frequency: cephalalgia, chronic paresthesias, dizziness or
      hypotension, visual disturbances, and tinnitus. In univariate analysis, ET
      related NS resulted more frequently in young people (P = 0.017) and in females (P
      = 0.025). We found a higher prevalence of JAK2V617F mutation in ET-related NS
      patients (P = 0.021). In multivariate analysis, gender (P = 0.024) and JAK2V617F
      mutation (P = 0.041) remained significantly associated with the development of ET
      related NS, with a risk of about four times higher for JAK2V617F-mutated patients
      (OR = 3.75). Ninety-seven of 101 patients with ET-related NS received an
      antiplatelet (AP) agent at the time of NS, whereas only selected high-risk ET
      related NS patients were treated with a cytoreductive drug, according to the
      published guidelines and similarly to patients without NS. We observed that only
      32 of 97 (33%) patients with ET-related NS achieved a complete response after AP
      treatment. Among the 65 non-responder patients, 36 (55.4%) improved NS after the
      introduction of cytoreductive therapy; therefore, the addition of cytoreductive
      treatment should be considered in this setting. 

PMID- 26205462
TI  - Impact of the Interdecadal Pacific Oscillation on Tropical Cyclone Activity in
      the North Atlantic and Eastern North Pacific.
AB  - Tropical cyclones (TCs) are among the most devastating weather systems affecting
      the United States and Central America (USCA). Here we show that the Interdecadal
      Pacific Oscillation (IPO) strongly modulates TC activity over the North Atlantic
      (NA) and eastern North Pacific (eNP). During positive IPO phases, less (more) TCs
      were observed over NA (eNP), likely due to the presence of stronger (weaker)
      vertical wind shear and the resulting changes in genesis potential. Furthermore,
      TCs over NA tend to keep their tracks more eastward and recurve at lower
      latitudes during positive IPO phases. Such variations are largely determined by
      changes in steering flow instead of changes in genesis locations. Over the eNP,
      smaller track variations are observed at different IPO phases with stable,
      westward movements of TCs prevailing. These findings have substantial
      implications for understanding decadal to inter-decadal fluctuations in the risk
      of TC landfalls along USCA coasts. 

PMID- 26205461
TI  - Number of episodes of reduced fetal movement at term: association with adverse
      perinatal outcome.
AB  - OBJECTIVE: The aims of this study were evaluation of the association of reduced
      fetal movements (RFM) and small-for-gestational-age (SGA) birth at term and to
      explore if fetal and maternal outcomes are different with single vs repeated
      episodes of RFM and normal fetal assessment test results. STUDY DESIGN: This was
      a retrospective cohort study of all singleton pregnancies referred for RFMs at a
      tertiary fetal medicine unit from January 2008 through September 2014. Ultrasound
      and Doppler indices were obtained from a computerized ultrasound database and
      pregnancy outcome was collected from hospital records. RESULTS: Of the 21,944
      women with a singleton pregnancy booked for maternity care during the study
      period, 1234 women (5.62%) reported RFMs >36+0 weeks. Of these, 1029 women
      (83.4%) reported a single episode of RFM and 205 (16.6%) had >=2 presentations
      for RFM. Women with repeated RFMs had a significantly higher mean uterine artery
      pulsatility index in the second trimester. The prevalence of SGA baby at birth in
      women presenting with a single episode as compared to repeated episodes of RFM
      was 9.8% and 44.2%, respectively (odds ratio, 7.3; 95% confidence interval, 5.1
      10.4; P < .05). CONCLUSION: Repeated episodes of RFMs at term are more likely to
      occur in women with high second-trimester uterine artery Doppler resistance
      indices and are strongly associated with the birth of SGA infants. Women
      presenting with repeated episodes of RFM should be treated as being at high risk
      of placental dysfunction irrespective of the results of prenatal ultrasound and
      Doppler assessment.

PMID- 26205463
TI  - Malaria: Hitting all stages of the parasite life cycle.

PMID- 26205464
TI  - Creating value with financially adaptive clinical trials.

PMID- 26205465
TI  - Regenerative medicine: Inhibiting prostaglandin breakdown triggers tissue
      regeneration.

PMID- 26205466
TI  - Antifungal drugs: Designer non-toxic derivatives dodge resistance.

PMID- 26205467
TI  - Assessing drug safety in human tissues - what are the barriers?

PMID- 26205468
TI  - Effect of religiosity/spirituality and sense of coherence on depression within a
      rural population in Greece: the Spili III project.
AB  - BACKGROUND: Recent research has addressed the hypothesis that
      religiosity/spirituality and sense of coherence buffer the negative effects of
      stress on numerous health issues. The aim of the current study was to further
      this work by exploring potential links between psycho-social factors such as
      religiosity/spirituality and sense of coherence with depression. METHODS: A total
      number of 220 subjects of the SPILI III cohort (1988-2012) attending a primary
      care setting in the town of Spili on rural Crete represented the target group.
      All participants underwent a standardized procedure. Validated questionnaires
      were used to evaluate sense of coherence, depression levels and religious and
      spiritual beliefs. A multiple linear regression analysis of the Beck Depression
      Inventory Scale (BDI) in relation to demographic characteristics, scores on the
      Royal Free Interview for Spiritual and Religious Beliefs scale (RFI-SRB) and
      Sense of Coherence scale (SOC) was performed. RESULTS: A significant inverse
      association was found between BDI and RFI-SRB scale (B-coef = -0.6999, p <
      0.001), as well as among BDI and SOC scale (B-coef = -0.556, p < 0.001).
      CONCLUSIONS: The findings of the current observational study indicate that highly
      religious participants are less likely to score high in the depression scale.
      Furthermore, participants with high SOC scored significantly lower in the BDI
      scale. Further research is required in order to explore the potential effect of
      SOC and religiosity/spirituality on mental health.

PMID- 26205469
TI  - Effects of cognitive appraisal and mental workload factors on performance in an
      arithmetic task.
AB  - We showed in a previous study an additive interaction between intrinsic and
      extraneous cognitive loads and of participants' alertness in an 1-back working
      memory task. The interaction between intrinsic and extraneous cognitive loads was
      only observed when participants' alertness was low (i.e. in the morning). As
      alertness is known to reflect an individual's general functional state, we
      suggested that the working memory capacity available for germane cognitive load
      depends on a participant's functional state, in addition to intrinsic and
      extraneous loads induced by the task and task conditions. The relationships
      between the different load types and their assessment by specific load measures
      gave rise to a modified cognitive load model. The aim of the present study was to
      complete the model by determining to what extent and at what processing level an
      individual's characteristics intervene in order to implement efficient strategies
      in a working memory task. Therefore, the study explored participants' cognitive
      appraisal of the situation in addition to the load factors considered previously
      task difficulty, time pressure and alertness. Each participant performed a mental
      arithmetic task in four different cognitive load conditions (crossover of two
      task difficulty conditions and of two time pressure conditions), both while their
      alertness was low (9 a.m.) and high (4 p.m.). Results confirmed an additive
      effect of task difficulty and time pressure, previously reported in the 1-back
      memory task, thereby lending further support to the modified cognitive load
      model. Further, in the high intrinsic and extraneous load condition, performance
      was reduced on the morning session (i.e. when alertness was low) on one hand, and
      in those participants' having a threat appraisal of the situation on the other
      hand. When these factors were included into the analysis, a performance drop
      occurred in the morning irrespective of cognitive appraisal, and with threat
      appraisal in the afternoon (i.e. high alertness). Taken together, these findings
      indicate that mental overload can be the result of a combination of subject
      related characteristics, including alertness and cognitive appraisal, in addition
      to well-documented task-related components (intrinsic and extraneous load). As
      the factors investigated in the study are known to be critically involved in a
      number of real job-activities, the findings suggest that solutions designed to
      reduce incidents and accidents at work should consider the situation from a
      global perspective, including individual characteristics, task parameters, and
      work organization, rather than dealing with each factor separately. 

PMID- 26205470
TI  - Awareness of cervical cancer risk factors and symptoms: cross-sectional community
      survey in post-conflict northern Uganda.
AB  - BACKGROUND: Lack of awareness of risk factors and symptoms for cancer may lead to
      late diagnosis and poor prognosis. OBJECTIVE: We assessed community awareness
      about cervical cancer risk factors and symptoms and perceptions about prevention
      and cure of cervical cancer in order to contribute data to inform interventions
      to improve cervical cancer survival. DESIGN: Cross-sectional population-based
      survey. SETTING AND PARTICIPANTS: We conducted this study in Gulu, a post
      conflict district in Uganda in 2012. The sample included 448 persons aged 18
      years and above, selected through a multi-stage stratified cluster sampling
      process. DATA COLLECTION METHODS AND ANALYSIS: We collected data using a
      pretested structured questionnaire. Logistic regressions were used to determine
      magnitudes of associations between socio-demographic and outcome variables.
      RESULTS: Most participants (444/448) had heard about cervical cancer. Known risk
      factors including multiple sexual partners, human papillomavirus infection, and
      early onset of sexual activity, were recognized by 88%, 82%, and 78% of
      respondents respectively. 63% of participants believed that prolonged use of
      family planning pills and injections caused cervical cancer. The majority of
      participants recognized symptoms of cervical cancer including inter-menstrual
      bleeding (85%), post-menopausal bleeding (84%), and offensive vaginal discharge
      (83%). 70% of participants believed that cervical cancer is preventable and 92%
      believed that it could be cured if diagnosed at an early stage. DISCUSSION AND
      CONCLUSIONS: Recognition of cervical cancer risk factors and symptoms was high
      among study participants. Targeted interventions including increasing
      availability of HPV vaccination, population-based cervical screening and
      diagnostic services can translate high awareness into actual benefits.

PMID- 26205471
TI  - Expression of proteins involved in DNA damage response in familial and sporadic
      breast cancer patients.
AB  - Understanding the expression of proteins involved in DNA damage response could
      improve knowledge of the pathways that contribute to familial and sporadic breast
      cancer (BC). We aimed to assess the different roles of BRCA1, poly(ADP-ribose)
      polymerase-1 (PARP1), BRCT-repeat inhibitor of hTERT expression (BRIT1) and novel
      SWItch 5 (SWI5) expression in 130 sporadic and 73 familial BC samples, by
      immunohistochemistry. In the sporadic group, negative nuclear BRCA1 (nBRCA1)
      expression was associated with positive PgR (p = 0.037). Negative association was
      found between nBRCA1 expression and HER2 (p = 0.001). In the familial group,
      nBRCA1 expression was associated with ER (p = 0.002). Reduced nBRCA1 expression
      was associated with higher histological grade and positive Ki67 both in sporadic
      (p = 0.0010, p = 0.047) and familial groups (p < 0.001, p = 0.001). Nuclear PARP1
      (nPARP1) expression was associated with histological grade (p = 0.035) and
      positive PgR (p = 0.047) in sporadic cases. High cytoplasmic and low nuclear
      BRIT1 (cBRIT1 and nBRIT1) expression were associated with high histological grade
      in the familial group (p = 0.013, p = 0.025). Various statistical associations
      between the protein expressions were observed in the sporadic group, while in
      familial group only few associations were found. Univariate analyses showed that
      nPARP1 expression is able to discriminate between sporadic and familial tumors
      (OR 2.80, p = 0.002). Multivariate analyses proved that its overexpression is an
      independent factor associated with a high risk of sporadic tumor (OR 2.96, p =
      0.017). Our findings indicate that nPARP1 expression is an independent factor for
      sporadic BCs and PARP1 inhibitors could be a promising therapy for different
      phenotypes.

PMID- 26205472
TI  - HPVbase--a knowledgebase of viral integrations, methylation patterns and
      microRNAs aberrant expression: As potential biomarkers for Human papillomaviruses
      mediated carcinomas.
AB  - Human papillomaviruses (HPVs) are extremely associated with different carcinomas.
      Despite consequential accomplishments, there is still need to establish more
      promising biomarkers to discriminate cancerous progressions. Therefore, we have
      developed HPVbase (http://crdd.osdd.net/servers/hpvbase/), a comprehensive
      resource for three major efficacious cancer biomarkers i.e. integration and
      breakpoint events, HPVs methylation patterns and HPV mediated aberrant expression
      of distinct host microRNAs (miRNAs). It includes clinically important 1257
      integrants and integration sites from different HPV types i.e. 16, 18, 31, 33 and
      45 associated with distinct histological conditions. An inclusive HPV integrant
      and breakpoints browser was designed to provide easy browsing and straightforward
      analysis. Our study also provides 719 major quantitative HPV DNA methylation
      observations distributed in 5 distinct HPV genotypes from higher to lower in
      numbers namely HPV 16 (495), HPV 18 (113), HPV45 (66), HPV 31 (34) and HPV 33
      (11). Additionally, we have curated and compiled clinically significant aberrant
      expression profile of 341 miRNAs including their target genes in distinct
      carcinomas, which can be utilized for miRNA therapeutics. A user-friendly web
      interface has been developed for easy data retrieval and analysis. We foresee
      that HPVbase an integrated and multi-comparative platform would facilitate
      reliable cancer diagnostics and prognosis. 

PMID- 26205473
TI  - Photoluminescent lateral-flow immunoassay revealed by graphene oxide: highly
      sensitive paper-based pathogen detection.
AB  - A paper-based lateral flow immunoassay for pathogen detection that avoids the use
      of secondary antibodies and is revealed by the photoluminescence quenching
      ability of graphene oxide is reported. Escherichia coli has been selected as a
      model pathogen. The proposed device is able to display a highly specific and
      sensitive performance with a limit of detection of 10 CFU mL(-1) in standard
      buffer and 100 CFU mL(-1) in bottled water and milk. This low-cost disposable and
      easy-to-use device will prove valuable for portable and automated diagnostics
      applications. 

PMID- 26205474
TI  - Transplantation of neurons derived from human iPS cells cultured on collagen
      matrix into guinea-pig cochleae.
AB  - The present study examined the efficacy of a neural induction method for human
      induced pluripotent stem (iPS) cells to eliminate undifferentiated cells and to
      determine the feasibility of transplanting neurally induced cells into guinea-pig
      cochleae for replacement of spiral ganglion neurons (SGNs). A stepwise method for
      differentiation of human iPS cells into neurons was used. First, a neural
      induction method was established on Matrigel-coated plates; characteristics of
      cell populations at each differentiation step were assessed. Second, neural stem
      cells were differentiated into neurons on a three-dimensional (3D) collagen
      matrix, using the same protocol of culture on Matrigel-coated plates; neuron
      subtypes in differentiated cells on a 3D collagen matrix were examined. Then,
      human iPS cell-derived neurons cultured on a 3D collagen matrix were transplanted
      into intact guinea-pig cochleae, followed by histological analysis. In vitro
      analyses revealed successful induction of neural stem cells from human iPS cells,
      with no retention of undifferentiated cells expressing OCT3/4. After the neural
      differentiation of neural stem cells, approximately 70% of cells expressed a
      neuronal marker, 90% of which were positive for vesicular glutamate transporter 1
      (VGLUT1). The expression pattern of neuron subtypes in differentiated cells on a
      3D collagen matrix was identical to that of the differentiated cells on Matrigel
      coated plates. In addition, the survival of transplant-derived neurons was
      achieved when inflammatory responses were appropriately controlled. Our
      preparation method for human iPS cell-derived neurons efficiently eliminated
      undifferentiated cells and contributed to the settlement of transplant-derived
      neurons expressing VGLUT1 in guinea-pig cochleae. Copyright (c) 2015 John Wiley &
      Sons, Ltd.

PMID- 26205479
TI  - Ambulatory Blood Pressures in Hypertensive Patients Treated With One
      Antihypertensive Agent: Differences Among Drug Classes and Among Drugs Belonging
      to the Same Class.
AB  - The authors investigated the differences in office and ambulatory blood pressure
      (BP) among major antihypertensive drug classes and among frequently used drugs in
      each class in 22,617 patients treated with monotherapy from the Spanish ABPM
      Registry. Using thiazides as the reference group, patients treated with calcium
      channel blockers have significantly (P<.01) elevated ambulatory BP and less
      ambulatory control after adjusting for confounders. Inside each class, no
      significant differences were observed among thiazides or angiotensin receptor
      blockers. Atenolol and bisoprolol among beta-blockers, amlodipine among calcium
      channel blockers, and lisinopril and enalapril among angiotensin-converting
      enzyme inhibitors exhibited lower ambulatory BP and better control than other
      agents. Differences exist among antihypertensive drug classes and among different
      compounds in each class with respect to ambulatory BP control. This can help
      physicians choose among drug classes and among compounds in each class if BP
      reduction is the main objective of treatment. 

PMID- 26205480
TI  - Return to sport: Does excellent 6-month strength and function following ACL
      reconstruction predict midterm outcomes?
AB  - PURPOSE: The purpose of this study was to determine whether patients with
      excellent 6-month functional testing after ACL reconstruction had (1) higher risk
      of subsequent ACL tears, (2) superior knee function, and (3) increased activity
      levels compared to those with delayed clearance for return to sports at midterm
      follow-up. METHODS: A total of 223 patients underwent primary ACL reconstruction
      by a single surgeon and had functional and isokinetic testing performed 6 months
      post-operatively between 1998 and 2005. Of the 223 patients, 52 (23 %) made the
      excellent group and were allowed return to sport at 6 months, and the remaining
      171 (77 %) constituted the delayed group. Rate of ACL graft tear and native
      contralateral ACL tear was compared between groups. In addition, IKDC and Tegner
      scores were compared at a mean 4-year follow-up. RESULTS: The graft rupture rate
      was similar in the excellent group (3.8 %, n = 2) compared to the delayed group
      (4.7 %, n = 8; p = 0.30). However, there was a higher rate of contralateral ACL
      tear in the excellent group (15.4 %, n = 8 vs. 5.3 %, n = 9; p = 0.003). The
      excellent 6-month group had superior IKDC scores (94.3 +/- 6.4 vs. 90.9 +/- 9.7;
      p = 0.04) and Tegner scores (6.6 +/- 1.8 vs. 5.7 +/- 1.6; p = 0.01). CONCLUSION:
      Patients with an excellent performance on their isokinetic strength and
      functional testing at 6 months after ACL reconstruction have superior knee
      function and higher activity levels at midterm follow-up. However, these patients
      appear to be at greater risk of contralateral ACL injury, which may be related to
      their increased activity level. When isokinetic and functional testing is used
      for return-to-sport decisions, physicians should caution patients about the risk
      of contralateral ACL injury for high performing patients. LEVEL OF EVIDENCE:
      Retrospective Review with Control, Level III.

PMID- 26205481
TI  - Platelet and not erythrocyte microparticles are procoagulant in transfused
      thalassaemia major patients.
AB  - The level of circulating platelet-, erythrocyte-, leucocyte- and endothelial
      derived microparticles detected by high-sensitivity flow cytometry was
      investigated in 37 beta-thalassaemia major patients receiving a regular
      transfusion regimen. The phospholipid procoagulant potential of the circulating
      microparticles and the microparticle-dependent tissue factor activity were
      evaluated. A high level of circulating erythrocyte- and platelet-microparticles
      was found. In contrast, the number of endothelial microparticles was within the
      normal range. Platelet microparticles were significantly higher in splenectomized
      than in non-splenectomized patients, independent of platelet count (P < 0.001).
      Multivariate analysis indicated that phospholipid-dependent procoagulant activity
      was influenced by both splenectomy (P = 0.001) and platelet microparticle level
      (P < 0.001). Erythrocyte microparticles were not related to splenectomy, appear
      to be devoid of proper procoagulant activity and no relationship between their
      production and haemolysis, dyserythropoiesis or oxidative stress markers could be
      established. Intra-microparticle labelling with anti-HbF antibodies showed that
      they originate only partially (median of 28%) from thalassaemic erythropoiesis.
      In conclusion, when beta-thalassaemia major patients are intensively transfused,
      the procoagulant activity associated with thalassaemic erythrocyte microparticles
      is probably diluted by transfusions. In contrast, platelet microparticles, being
      both more elevated and more procoagulant, especially after splenectomy, may
      contribute to the residual thrombotic risk reported in splenectomized multi
      transfused beta-thalassaemia major patients. 

PMID- 26205482
TI  - Assembly of a photosynthetic reaction center with ABA tri-block polymersomes:
      highlights on protein localization.
AB  - The reconstitution of the integral membrane protein photosynthetic reaction
      center (RC) in polymersomes, i.e. artificial closed vesicles, was achieved by the
      micelle-to-vesicle transition technique, a very mild protocol based on size
      exclusion chromatography often used to drive the incorporation of proteins
      contemporarily to liposome formation. An optimized protocol was used to
      successfully reconstitute the protein in a fully active state in polymersomes
      formed by the tri-block copolymers PMOXA22-PDMS61-PMOXA22. The RC is very
      sensitive to its solubilizing environment and was used to probe the positioning
      of the protein in the vesicles. According to charge-recombination experiments and
      to the enzymatic activity assay, the RC is found to accommodate in the PMOXA22
      region of the polymersome, facing the water bulk solution, rather than in the
      PDMS61 transmembrane-like region. Furthermore, polymersomes were found to
      preserve protein integrity efficiently as the biomimetic lipid bilayers but show
      a much longer temporal stability than lipid based vesicles. 

PMID- 26205483
TI  - Expression of Concern: MicroRNA profile of tumorigenic cells during
      carcinogenesis of lung adenocarcinoma by Zhao, ZG, Jin, JY, Zhang, AM, Zhang, LP,
      Wang, XX, Sun, JG, and Chen, ZT. J Cell Biochem, 116: 458-466.
      doi:10.1002/jcb.24999.

PMID- 26205488
TI  - 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015).

PMID- 26205489
TI  - Regulation of the p53 response and its relationship to cancer.
AB  - p53 has been studied intensively as a major tumour suppressor that detects
      oncogenic events in cancer cells and eliminates them through senescence (a
      permanent non-proliferative state) or apoptosis. Consistent with this role, p53
      activity is compromised in a high proportion of all cancer types, either through
      mutation of the TP53 gene (encoding p53) or changes in the status of p53
      modulators. p53 has additional roles, which may overlap with its tumour
      suppressive capacity, in processes including the DNA damage response, metabolism,
      aging, stem cell differentiation and fertility. Moreover, many mutant p53
      proteins, termed 'gain-of-function' (GOF), acquire new activities that help drive
      cancer aggression. p53 is regulated mainly through protein turnover and operates
      within a negative-feedback loop with its transcriptional target, MDM2 (murine
      double minute 2), an E3 ubiquitin ligase which mediates the ubiquitylation and
      proteasomal degradation of p53. Induction of p53 is achieved largely through
      uncoupling the p53-MDM2 interaction, leading to elevated p53 levels. Various
      stress stimuli acting on p53 (such as hyperproliferation and DNA damage) use
      different, but overlapping, mechanisms to achieve this. Additionally, p53
      activity is regulated through critical context-specific or fine-tuning events,
      mediated primarily through post-translational mechanisms, particularly multi-site
      phosphorylation and acetylation. In the present review, I broadly examine these
      events, highlighting their regulatory contributions, their ability to integrate
      signals from cellular events towards providing most appropriate response to
      stress conditions and their importance for tumour suppression. These are
      fascinating aspects of molecular oncology that hold the key to understanding the
      molecular pathology of cancer and the routes by which it may be tackled
      therapeutically. 

PMID- 26205491
TI  - A recycling pathway for cyanogenic glycosides evidenced by the comparative
      metabolic profiling in three cyanogenic plant species.
AB  - Cyanogenic glycosides are phytoanticipins involved in plant defence against
      herbivores by virtue of their ability to release toxic hydrogen cyanide (HCN)
      upon tissue disruption. In addition, endogenous turnover of cyanogenic glycosides
      without the liberation of HCN may offer plants an important source of reduced
      nitrogen at specific developmental stages. To investigate the presence of
      putative turnover products of cyanogenic glycosides, comparative metabolic
      profiling using LC-MS/MS and high resolution MS (HR-MS) complemented by ion
      mobility MS was carried out in three cyanogenic plant species: cassava, almond
      and sorghum. In total, the endogenous formation of 36 different chemical
      structures related to the cyanogenic glucosides linamarin, lotaustralin,
      prunasin, amygdalin and dhurrin was discovered, including di- and tri-glycosides
      derived from these compounds. The relative abundance of the compounds was
      assessed in different tissues and developmental stages. Based on results common
      to the three phylogenetically unrelated species, a potential recycling endogenous
      turnover pathway for cyanogenic glycosides is described in which reduced nitrogen
      and carbon are recovered for primary metabolism without the liberation of free
      HCN. Glycosides of amides, carboxylic acids and 'anitriles' derived from
      cyanogenic glycosides appear as common intermediates in this pathway and may also
      have individual functions in the plant. The recycling of cyanogenic glycosides
      and the biological significance of the presence of the turnover products in
      cyanogenic plants open entirely new insights into the multiplicity of biological
      roles cyanogenic glycosides may play in plants. 

PMID- 26205492
TI  - Hypothalamic NUCKS regulates peripheral glucose homoeostasis.
AB  - Nuclear ubiquitous casein and cyclin-dependent kinase substrate (NUCKS) is highly
      expressed in the brain and peripheral metabolic organs, and regulates
      transcription of a number of genes involved in insulin signalling. Whole-body
      depletion of NUCKS (NKO) in mice leads to obesity, glucose intolerance and
      insulin resistance. However, a tissue-specific contribution of NUCKS to the
      observed phenotypes remains unknown. Considering the pivotal roles of insulin
      signalling in the brain, especially in the hypothalamus, we examined the
      functions of hypothalamic NUCKS in the regulation of peripheral glucose
      metabolism. Insulin signalling in the hypothalamus was impaired in the NKO mice
      when insulin was delivered through intracerebroventricular injection. To validate
      the hypothalamic specificity, we crossed transgenic mice expressing Cre
      recombinase under the Nkx2.1 promoter with floxed NUCKS mice to generate mice
      with hypothalamus-specific deletion of NUCKS (HNKO). We fed the HNKO and
      littermate control mice with a normal chow diet (NCD) and a high-fat diet (HFD),
      and assessed glucose tolerance, insulin tolerance and metabolic parameters. HNKO
      mice showed mild glucose intolerance under an NCD, but exacerbated obesity and
      insulin resistance phenotypes under an HFD. In addition, NUCKS regulated levels
      of insulin receptor in the brain. Unlike HNKO mice, mice with immune-cell
      specific deletion of NUCKS (VNKO) did not develop obesity or insulin-resistant
      phenotypes under an HFD. These studies indicate that hypothalamic NUCKS plays an
      essential role in regulating glucose homoeostasis and insulin signalling in vivo.

PMID- 26205490
TI  - KEAP1-NRF2 signalling and autophagy in protection against oxidative and reductive
      proteotoxicity.
AB  - Maintaining cellular redox status to allow cell signalling to occur requires
      modulation of both the controlled production of oxidants and the thiol-reducing
      networks to allow specific regulatory post-translational modification of protein
      thiols. The oxidative stress hypothesis captured the concept that overproduction
      of oxidants can be proteotoxic, but failed to predict the recent finding that
      hyperactivation of the KEAP1-NRF2 system also leads to proteotoxicity.
      Furthermore, sustained activation of thiol redox networks by KEAP1-NRF2 induces a
      reductive stress, by decreasing the lifetime of necessary oxidative post
      translational modifications required for normal metabolism or cell signalling. In
      this context, it is now becoming clear why antioxidants or hyperactivation of
      antioxidant pathways with electrophilic therapeutics can be deleterious.
      Furthermore, it suggests that the autophagy-lysosomal pathway is particularly
      important in protecting the cell against redox-stress-induced proteotoxicity,
      since it can degrade redox-damaged proteins without causing aberrant changes to
      the redox network needed for metabolism or signalling. In this context, it is
      important to understand: (i) how NRF2-mediated redox signalling, or (ii) the
      autophagy-mediated antioxidant/reductant pathways sense cellular damage in the
      context of cellular pathogenesis. Recent studies indicate that the modification
      of protein thiols plays an important role in the regulation of both the KEAP1
      NRF2 and autophagy pathways. In the present review, we discuss evidence
      demonstrating that the KEAP1-NRF2 pathway and autophagy act in concert to combat
      the deleterious effects of proteotoxicity. These findings are discussed with a
      special emphasis on their impact on cardiovascular disease and neurodegeneration.

PMID- 26205493
TI  - Gambogic acid inhibits osteoclast formation and ovariectomy-induced osteoporosis
      by suppressing the JNK, p38 and Akt signalling pathways.
AB  - Excessive osteoclast formation and bone resorption are key causes of
      osteoporosis. Natural compounds can serve as alternative therapeutic agents for
      the prevention and treatment of osteoporosis, and some natural compounds may have
      advantages over traditional drugs. In the present paper, we report that the
      natural compound GBA (gambogic acid), which is bioavailable, effective and less
      toxic, inhibits osteoclast formation, thereby attenuating osteoclastic bone
      resorption in vitro. Further in vivo studies demonstrated that GBA prevented
      ovariectomy-induced bone loss in a dose-dependent manner. Moreover, we
      demonstrated that GBA suppressed RANKL (receptor activator of nuclear factor
      kappaB ligand)-induced JNK (c-Jun N-terminal kinase), p38 and Akt
      phosphorylation. Taken together, our results demonstrate that GBA inhibits
      osteoclast formation in vitro and in vivo, suggesting that it is of potential
      value in the treatment of osteoclast-related diseases. 

PMID- 26205494
TI  - Cyclin Y phosphorylation- and 14-3-3-binding-dependent activation of PCTAIRE
      1/CDK16.
AB  - PCTAIRE-1 [also known as cyclin-dependent kinase 16 (CDK16)] is implicated in
      various physiological processes such as neurite outgrowth and vesicle
      trafficking; however, its molecular regulation and downstream targets are largely
      unknown. Cyclin Y has recently been identified as a key interacting/activating
      cyclin for PCTAIRE-1; however, the molecular mechanism by which it activates
      PCTAIRE-1 is undefined. In the present study, we initially performed protein
      sequence analysis and identified two candidate phosphorylation sites (Ser(12) and
      Ser(336)) on cyclin Y that might be catalysed by PCTAIRE-1. Although in vitro
      peptide analysis favoured Ser(12) as the candidate phosphorylation site,
      immunoblot analysis of cell lysates that had been transfected with wild-type (WT)
      or kinase-inactive (KI) PCTAIRE-1 together with WT or phospho-deficient mutants
      of cyclin Y suggested Ser(336), but not Ser(12), as a PCTAIRE-1-dependent
      phosphorylation site. Monitoring phosphorylation of Ser(336) may provide a useful
      read-out to assess cellular activity of PCTAIRE-1 in vivo; however, a phospho
      deficient S336A mutant displayed normal interaction with PCTAIRE-1. Unbiased mass
      spectrometry and targeted mutagenesis analysis of cyclin Y identified key
      phosphorylation sites (Ser(100) and Ser(326)) required for 14-3-3 binding.
      Recombinant WT cyclin Y, but not a S100A/S326A mutant, prepared in COS-1 cells co
      purified with 14-3-3 and was able to activate bacterially expressed recombinant
      PCTAIRE-1 in cell-free assays. Finally, we observed that recently identified
      PCTAIRE-1 variants found in patients with intellectual disability were unable to
      interact with cyclin Y, and were inactive enzymes. Collectively, the present work
      has revealed a new mechanistic insight into activation of PCTAIRE-1, which is
      mediated through interaction with the phosphorylated form of cyclin Y in complex
      with 14-3-3. 

PMID- 26205495
TI  - Crystal structure of human platelet phosphofructokinase-1 locked in an activated
      conformation.
AB  - Phosphofructokinase-1 (Pfk) acts as the main control point of flux through
      glycolysis. It is involved in complex allosteric regulation and Pfk mutations
      have been linked to cancer development. Whereas the 3D structure and structural
      basis of allosteric regulation of prokaryotic Pfk has been studied in great
      detail, our knowledge about the molecular basis of the allosteric behaviour of
      the more complex mammalian Pfk is still very limited. To characterize the
      structural basis of allosteric regulation, the subunit interfaces and the
      functional consequences of modifications in Tarui's disease and cancer, we
      analysed the physiological homotetramer of human platelet Pfk at up to 2.67 A
      resolution in two crystal forms. The crystallized enzyme is permanently activated
      by a deletion of the 22 C-terminal residues. Complex structures with ADP and
      fructose-6-phosphate (F6P) and with ATP suggest a role of three aspartates in the
      deprotonation of the OH-nucleophile of F6P and in the co-ordination of the
      catalytic magnesium ion. Changes at the dimer interface, including an asymmetry
      observed in both crystal forms, are the primary mechanism of allosteric
      regulation of Pfk by influencing the F6P-binding site. Whereas the nature of this
      conformational switch appears to be largely conserved in bacterial, yeast and
      mammalian Pfk, initiation of these changes differs significantly in eukaryotic
      Pfk. 

PMID- 26205496
TI  - GlxA is a new structural member of the radical copper oxidase family and is
      required for glycan deposition at hyphal tips and morphogenesis of Streptomyces
      lividans.
AB  - Streptomyces lividans displays a distinct dependence on copper to fully initiate
      morphological development. Evidence has accumulated to implicate the
      participation of an extracytoplasmic cuproenzyme in morphogenesis. In the present
      study, we show that GlxA fulfils all criteria to be that cuproenzyme. GlxA is
      membrane associated and has an active site consisting of a mononuclear copper and
      a cross-linked Y-C cofactor. The domain organization of the tertiary structure
      defines GlxA as a new structural member of the mono-copper oxidase family, with
      copper co-ordination geometry similar to, but spectroscopically distinct from
      fungal galactose oxidase (Gox). EPR spectroscopy reveals that the oxidation of
      cupric GlxA generates a protein radical residing on the Y-C cross-link. A variety
      of canonical Gox substrates (including D-galactose) were tested but none were
      readily turned over by GlxA. A glxA null-mutant leads to loss of glycan
      accumulation at hyphal tips and consequently a drastically changed morphology
      both on solid substrates and in liquid-grown environments, a scenario similarly
      observed in the absence of the neighbouring glycan synthase CslA (cellulase
      synthase-like protein). In addition the glxA mutant has lost the stimulation of
      development by copper, supporting a model whereby the enzymatic action of GlxA on
      the glycan is required for development and morphology. From a biotechnology
      perspective, the open mycelium morphology observed with the glxA mutant in
      submerged culture has implications for use as an enzyme production host. 

PMID- 26205497
TI  - Role for RalA downstream of Rac1 in skeletal muscle insulin signalling.
AB  - Insulin-stimulated glucose uptake in skeletal muscle is mediated by the
      translocation of the glucose transporter GLUT4 from intracellular storage sites
      to the plasma membrane. The small GTPase Rac1 has been implicated in this insulin
      signalling, but the mechanism whereby Rac1 stimulates GLUT4 translocation remains
      obscure. In the present study, we examined the role of the small GTPase RalA
      downstream of Rac1 in skeletal muscle fibres isolated from genetically modified
      mice. A dominant-negative mutant of RalA, when ectopically overexpressed,
      significantly reduced GLUT4 translocation in response to insulin or either one of
      constitutively activated mutants of Rac1 and its upstream regulators, including
      the guanine-nucleotide-exchange factor FLJ00068, the protein kinase Akt2 and
      phosphoinositide 3-kinase. Constitutively activated Rac1 also failed to induce
      GLUT4 translocation in mouse skeletal muscle fibres in which the expression of
      RalA was abrogated by specific siRNA molecules. Furthermore, we applied a novel
      approach to detect the activated form of RalA in situ by immunofluorescence
      microscopy of mouse skeletal muscle fibres, demonstrating that constitutively
      activated mutants of Rac1 and its upstream regulators as well as insulin indeed
      cause the activation of RalA. Notably, this RalA activation was remarkably
      impaired in rac1-deficient skeletal muscle fibres. Taken together, these results
      provide evidence that RalA is indeed activated and involved in the regulation of
      GLUT4 translocation in response to insulin downstream of Rac1 in mouse skeletal
      muscle. 

PMID- 26205498
TI  - An intrinsically disordered region of RPN10 plays a key role in restricting
      ubiquitin chain elongation in RPN10 monoubiquitination.
AB  - Despite being a common mechanism in eukaryotes, the process by which protein
      monoubiquitination is produced and regulated in vivo is not completely
      understood. We present here the analysis of the process of monoubiquitination of
      the proteasomal subunit Rpn10 (regulatory particle non-ATPase 10), involved in
      the recruitment of polyubiquitinated substrates. Rpn10 is monoubiquitinated in
      vivo by the Nedd4 (neural precursor cell expressed developmentally down-regulated
      4) enzyme Rsp5 (reverses SPT-phenotype protein 5) and this modification impairs
      the interaction of Rpn10 with substrates, having a regulatory effect on
      proteasome function. Remarkably, a disordered region near the ubiquitin
      interacting motif of Rpn10 plays a role in the restriction of the polyubiquitin
      extension activity of Rsp5. Mutations in this disordered region promote ubiquitin
      chain extension of Rpn10. Thus, our work sheds light on the molecular basis and
      the functional relevance of a type of monoubiquitination that is driven by the
      substrate. Moreover, we uncover a putative role for disordered regions in
      modulating ubiquitin-protein ligation. 

PMID- 26205499
TI  - DDB2 is involved in ubiquitination and degradation of PAQR3 and regulates
      tumorigenesis of gastric cancer cells.
AB  - DDB2 (damage-specific DNA-binding protein 2) is the product of the xeroderma
      pigmentosum group E gene which is involved in the initiation of nucleotide
      excision repair via an ubiquitin ligase complex together with DDB1 and CUL4A
      (cullin 4A). PAQR3 (progestin and adipoQ receptor family member III) is a newly
      discovered tumour suppressor that is implicated in the development of many types
      of human cancers. In the present paper, we report that DDB2 is involved in
      ubiquitination and degradation of PAQR3. DDB2 is able to interact with PAQR3 in
      vivo and in vitro. Both overexpression and knockdown experiments reveal that the
      protein expression level, protein stability and polyubiquitination of PAQR3 are
      changed by DDB2. Negative regulation of EGF (epidermal growth factor)- and
      insulin-induced signalling by PAQR3 is also altered by DDB2. At the molecular
      level, Lys(61) of PAQR3 is targeted by DDB2 for ubiquitination. The cell
      proliferation rate and migration of gastric cancer cells are inhibited by DDB2
      knockdown and such effects are abrogated by PAQR3 knockdown, indicating that the
      effect of DDB2 on the cancer cells is mediated by PAQR3. Collectively, our
      studies not only pinpoint that DDB2 is a post-translational regulator of PAQR3,
      but also indicate that DDB2 may play an active role in tumorigenesis via
      regulating PAQR3. 

PMID- 26205500
TI  - Nanoparticles speckled by ready-to-conjugate lanthanide complexes for multimodal
      imaging.
AB  - Multimodal and multifunctional contrast agents receive enormous attention in the
      biomedical imaging field. Such contrast agents are routinely prepared by the
      incorporation of organic molecules and inorganic nanoparticles (NPs) into host
      materials such as gold NPs, silica NPs, polymer NPs, and liposomes. Despite their
      non-cytotoxic nature, the large size of these NPs limits the in vivo distribution
      and clearance and inflames complex pharmacokinetics, which hinder the regulatory
      approval for clinical applications. Herein, we report a unique method that
      combines magnetic resonance imaging (MRI) and fluorescence imaging modalities
      together in nanoscale entities by the simple, direct and stable conjugation of
      novel biotinylated coordination complexes of gadolinium(III) to CdSe/ZnS quantum
      dots (QD) and terbium(III) to super paramagnetic iron oxide NPs (SPION) but
      without any host material. Subsequently, we evaluate the potentials of such
      lanthanide-speckled fluorescent-magnetic NPs for bioimaging at single-molecule,
      cell and in vivo levels. The simple preparation and small size make such
      fluorescent-magnetic NPs promising contrast agents for biomedical imaging.

PMID- 26205502
TI  - One Electron Makes Differences: From Heme {FeNO}(7) to {FeNO}(8).
AB  - The first X-ray single-crystal structure of a {FeNO}(8) porphyrin complex
      [Co(Cp)2][Fe(TFPPBr8)(NO)], and the structure of the {FeNO}(7) precursor
      [Fe(TFPPBr8)(NO)] are determined at 100 K. The two complexes are also
      characterized by FTIR and UV/Vis spectroscopy. [Fe(TFPPBr8)(NO)](-) shows
      distinct structural features in contrast to a nitrosyl iron(II) porphyrinate on
      the Fe-N-O(-) moiety, which include a much more bent Fe-N-O(-) angle (122.4(3)
      degrees ), considerably longer Fe-NO(-) (1.814(4)) and N-O(-) (1.194(5) A) bond
      distances. These and the about 180 cm(-1) downshift nu(N-O) stretch (1540 cm(-1))
      can be understood by the covalently bonding nature between the iron(II) and the
      NO(-) ligand which possesses a two-electron-occupied pi* orbital as a result of
      the reduction. The overall structural features of [Fe(TFPPBr8)(NO)](-) and
      [Fe(TFPPBr8)(NO)] suggest a low-spin state of the iron(II) atom at 100 K.

PMID- 26205501
TI  - Presentation of Acute Megakaryoblastic Leukemia Associated with a GATA-1 Mutation
      Mimicking the Eruption of Transient Myeloproliferative Disorder.
AB  - Children with trisomy 21 are prone to developing hematologic disorders, including
      transient myeloproliferative disorder (TMD) and acute megakaryoblastic leukemia
      (AMKL). The papulovesicular eruption of TMD provides an important clue to the
      diagnosis. In contrast, AMKL rarely has associated cutaneous findings. We report
      the case of a 22-month-old child with trisomy 21 who presented with the acute
      onset of diffusely scattered and crusted papules, plaques, and vesicles. A
      thorough infectious evaluation was negative and the patient was unresponsive to
      empiric antibiotic and antiinflammatory therapies. Complete blood count (CBC) was
      notable for mild pancytopenia, with a normal peripheral smear. Two weeks later he
      was reassessed and found to have a population of blasts on repeat CBC. Subsequent
      evaluation ultimately led to a diagnosis of AMKL. This is the first reported case
      of a cutaneous eruption in a young child with Down syndrome and transformed AMKL.
      When children with trisomy 21 present with the acute onset of crusted papules and
      vesicles that cannot be accounted for by an infectious etiology, a diagnosis of
      AMKL should be considered even in the absence of a history of TMD.

PMID- 26205503
TI  - Molecular cloning and characterization of satellite DNA sequences from
      constitutive heterochromatin of the habu snake (Protobothrops flavoviridis,
      Viperidae) and the Burmese python (Python bivittatus, Pythonidae).
AB  - Highly repetitive DNA sequences of the centromeric heterochromatin provide
      valuable molecular cytogenetic markers for the investigation of genomic
      compartmentalization in the macrochromosomes and microchromosomes of sauropsids.
      Here, the relationship between centromeric heterochromatin and karyotype
      evolution was examined using cloned repetitive DNA sequences from two snake
      species, the habu snake (Protobothrops flavoviridis, Crotalinae, Viperidae) and
      Burmese python (Python bivittatus, Pythonidae). Three satellite DNA (stDNA)
      families were isolated from the heterochromatin of these snakes: 168-bp PFL-MspI
      from P. flavoviridis and 196-bp PBI-DdeI and 174-bp PBI-MspI from P. bivittatus.
      The PFL-MspI and PBI-DdeI sequences were localized to the centromeric regions of
      most chromosomes in the respective species, suggesting that the two sequences
      were the major components of the centromeric heterochromatin in these organisms.
      The PBI-MspI sequence was localized to the pericentromeric region of four
      chromosome pairs. The PFL-MspI and the PBI-DdeI sequences were conserved only in
      the genome of closely related species, Gloydius blomhoffii (Crotalinae) and
      Python molurus, respectively, although their locations on the chromosomes were
      slightly different. In contrast, the PBI-MspI sequence was also in the genomes of
      P. molurus and Boa constrictor (Boidae), and additionally localized to the
      centromeric regions of eight chromosome pairs in B. constrictor, suggesting that
      this sequence originated in the genome of a common ancestor of Pythonidae and
      Boidae, approximately 86 million years ago. The three stDNA sequences showed no
      genomic compartmentalization between the macrochromosomes and microchromosomes,
      suggesting that homogenization of the centromeric and/or pericentromeric stDNA
      sequences occurred in the macrochromosomes and microchromosomes of these snakes. 

PMID- 26205504
TI  - Differential chromatin amplification and chromosome complements in the germline
      of Strongyloididae (Nematoda).
AB  - Nematodes of the genus Strongyloides are intestinal parasites of vertebrates
      including man. Currently, Strongyloides and its sister genus Parastrongyloides
      are being developed as models for translational and basic biological research.
      Strongyloides spp. alternate between parthenogenetic parasitic and single free
      living sexual generations, with the latter giving rise to all female parasitic
      progeny. Parastrongyloides trichosuri always reproduces sexually and may form
      many consecutive free-living generations. Although the free-living adults of both
      these species share a superficial similarity in overall appearance when compared
      to Caenorhabditis elegans, there are dramatic differences between them, in
      particular with respect to the organization of the germline. Here we address two
      such differences, which have puzzled investigators for several generations.
      First, we characterize a population of non-dividing giant nuclei in the distal
      gonad, the region that in C. elegans is populated by mitotically dividing
      germline stem cells and early meiotic cells. We show that in these nuclei,
      autosomes are present in higher copy numbers than X chromosomes. Consistently,
      autosomal genes are expressed at higher levels than X chromosomal ones,
      suggesting that these worms use differential chromatin amplification for
      controlling gene expression. Second, we address the lack of males in the progeny
      of free-living Strongyloides spp. We find that male-determining (nullo-X) sperm
      are present in P. trichosuri, a species known to produce male progeny, and absent
      in Strongyloides papillosus, which is consistent for a species that does not.
      Surprisingly, nullo-X sperm appears to be present in Strongyloides ratti, even
      though this species does not produce male progeny. This suggests that different
      species of Strongyloides employ various strategies to prevent the formation of
      males in the all-parasitic progeny of the free-living generation. 

PMID- 26205505
TI  - Child welfare caseworkers' characteristics and their attitudes toward non
      custodial fathers.
AB  - Despite increased attention to the caseworker's role in the successful engagement
      of fathers and in producing successful child welfare outcomes more generally,
      little is known about child welfare caseworkers' attitudes toward non-custodial
      fathers. Using generalized ordinal logistic regression to analyze attitudes in a
      sample of child welfare caseworkers from four U.S. states, the present study
      examines how caseworkers' demographic, education, and employment characteristics
      affect their attitudes toward non-custodial fathers. Race/ethnicity and
      employment characteristics predicted differences in opinion on whether fathers
      want to be involved, increase children's well-being, need help parenting, and
      whether involving fathers is troublesome and complicated. Results suggest that
      caseworkers' backgrounds serve as inputs into their approach to fathers and
      indicate a need for further study of the relationship between caseworkers'
      characteristics and attitudes, and how these might influence case outcomes. 

PMID- 26205506
TI  - Innate immune response during herpes simplex virus encephalitis and development
      of immunomodulatory strategies.
AB  - Herpes simplex viruses are large double-stranded DNA viruses. These viruses have
      the ability to establish a lifelong latency in sensory ganglia and to invade and
      replicate in the CNS. Apart from relatively benign mucosal infections, HSV is
      responsible for severe illnesses including HSV encephalitis (HSE). HSE is the
      most common cause of sporadic, potentially fatal viral encephalitis in Western
      countries. If left untreated, the mortality rate associated with HSE is
      approximately 70%. Despite antiviral therapy, the mortality is still higher than
      30%, and almost 60% of surviving individuals develop neurological sequelae. It is
      suggested that direct virus-related and indirect immune-mediated mechanisms
      contribute to the damages occurring in the CNS during HSE. In this manuscript, we
      describe the innate immune response to HSV, the development of HSE in mice knock
      out for proteins of the innate immune system as well as inherited deficiencies in
      key components of the signaling pathways involved in the production of type I
      interferon that could predispose individuals to develop HSE. Finally, we review
      several immunomodulatory strategies aimed at modulating the innate immune
      response at a critical time after infection that were evaluated in mouse models
      and could be combined with antiviral therapy to improve the prognosis of HSE. In
      conclusion, the cerebral innate immune response that develops during HSE is a
      "double-edged sword" as it is critical to control viral replication in the brain
      early after infection, but, if left uncontrolled, may also result in an
      exaggerated inflammatory response that could be detrimental to the host.

PMID- 26205507
TI  - Low Commission's recommendations on welfare advice in healthcare settings are
      welcome.

PMID- 26205508
TI  - GmSBH1, a homeobox transcription factor gene, relates to growth and development
      and involves in response to high temperature and humidity stress in soybean.
AB  - KEY MESSAGE: GmSBH1 involves in response to high temperature and humidity stress.
      Homeobox transcription factors are key switches that control plant development
      processes. Glycine max H1 Sbh1 (GmSBH1) was the first homeobox gene isolated from
      soybean. In the present study, the full ORF of GmSBH1 was isolated, and the
      encoded protein was found to be a typical class I KNOX homeobox transcription
      factor. Subcellular localization and transcriptional activation assays showed
      that GmSBH1 is a nuclear protein and possesses transcriptional activation
      activity in the homeodomain. The KNOX1 domain was found to play a clear role in
      suppressing the transcriptional activation activity of GmSBH1. GmSBH1 showed
      different expression levels among different soybean tissues and was involved in
      response to high temperature and humidity (HTH) stress in developing soybean
      seeds. The overexpression of GmSBH1 in Arabidopsis altered leaf and stoma
      phenotypes and enhanced seed tolerance to HTH stress. Overall, our results
      indicated that GmSBH1 is involved in growth, development, and enhances tolerance
      to pre-harvest seed deterioration caused by HTH stress in soybean.

PMID- 26205509
TI  - DhEFL2, 3 and 4, the three EARLY FLOWERING4-like genes in a Doritaenopsis hybrid
      regulate floral transition.
AB  - KEY MESSAGE: DhEFL2, 3 and 4 regulate the flowering of Doritaenopsis . These
      genes could rescue elf4-1 phenotype in Arabidopsis while its overexpression
      delayed flowering. Phalaenopsis are popular floral plants, and studies on orchid
      flowering genes could help develop off-season cultivars. Early flowering 4 (ELF4)
      of A. thaliana has been shown to be involved in photoperiod perception and
      circadian regulation. We isolated two members of the ELF4 family from
      Doritaenopsis hybrid (Doritaenopsis 'Tinny Tender' (Doritaenopsis Happy Smile *
      Happy Valentine)), namely, DhEFL2 and DhEFL3 (DhEFL4 has been previously cloned).
      Multiple alignment analysis of the deduced amino acid sequences of the three
      DhEFL homologs showed that DhEFL4 and DhEFL2 are similar with 72% identical amino
      acids, whereas DhEFL3 is divergent with 72% similarity with DhEFL2 and 68%
      similarity with DhEFL4. DhEFL3 forms a separate phylogenetic subgroup and is far
      away from DhEFL2 and DhEFL4. The diurnal expression patterns of DhEFL2, 3, and 4
      are similar in the long-day photoperiod conditions; however, in the short-day
      conditions, DhEFL3 is different from DhEFL2 and 4. For the DhEFL2, 3, and 4
      genes, the strongest audience expression organs are the stem, petal and bud,
      respectively. The ectopic expression of DhEFL2, 3, or 4 in transgenic A. thaliana
      plants (Ws-2 ecotype) showed novel phenotypes by late flowering and more rosette
      leaves. The ectopic expression of DhEFL2, 3, or 4 could complement the elf4-1
      flowering time and hypocotyl length defects in transgenic A. thaliana elf4-1
      mutant plants. These results strongly suggest that DhEFL2, 3, and 4 may be
      involved in regulation of flower formation and floral induction in Doritaenopsis.

PMID- 26205510
TI  - Extravascular stent management for migration of left renal vein endovascular
      stent in nutcracker syndrome.
AB  - BACKGROUND: Nutcracker syndrome is an entity resulting from left renal vein
      compression by the aorta and the superior mesenteric artery, which leads to
      symptoms of hematuria or left flank pain. The alternative option of endovascular
      or extravascular stenting is very appealing because of the minimal invasive
      procedures. Stents in the renal vein can cause fibromuscular hyperplasia,
      proximal migration or embolization. CASE PRESENTATION: A 30-year-old female was
      diagnosed with nutcracker syndrome for severe left flank pain. After failed
      conservative approach, she underwent endovascular stenting and subsequently
      developed recurrent symptom for stent migration one month postoperatively. She
      underwent successful extravascular stenting with complete symptom resolution.
      CONCLUSION: The extravascular stenting is an alternative option after migration
      of left renal vein endovascular stenting. The computed tomographic imaging was
      closely correlated to therapeutic interventions and stent migration.

PMID- 26205511
TI  - Braided tubular superelastic cables provide improved spinal stability compared to
      multifilament sublaminar cables.
AB  - This study investigates the use of braided tubular superelastic cables,
      previously used for sternum closure following sternotomy, as sublaminar fixation
      method. It compares the biomechanical performance of spinal instrumentation
      fixation systems with regular sublaminar cables and proprietary superelastic
      cables. A hybrid experimental protocol was applied to six porcine L1-L4 spinal
      segments to compare multifilament sublaminar cables (Atlas, Medtronic Sofamor
      Danek, Memphis, TN) with proprietary superelastic cables. First, intact total
      range of motion was determined for all specimens using pure moment loading.
      Second, pure moments were imposed to the instrumented specimens until these
      intact total ranges of motion were reproduced. Compared to the intact specimens,
      the use of superelastic cables resulted in stiffer instrumented specimens than
      the use of multifilament cables for all the loading modes except axial torsion.
      Consequently, the superelastic cables limited the instrumented segments mobility
      more than the multifilament cables. Spinal instrumentation fixation systems using
      superelastic cables could be a good alternative to conventional sublaminar cables
      as it maintains a constant stabilization of the spine during loading. 

PMID- 26205512
TI  - The relationship of women's status and empowerment with skilled birth attendant
      use in Senegal and Tanzania.
AB  - BACKGROUND: Maternal mortality remains unacceptably high in sub-Saharan Africa
      with 179,000 deaths occurring each year, accounting for 2-thirds of maternal
      deaths worldwide. Progress in reducing maternal deaths and increasing Skilled
      Birth Attendant (SBA) use at childbirth has stagnated in Africa. Although several
      studies demonstrate the important influences of women's status and empowerment on
      SBA use, this evidence is limited, particularly in Africa. Furthermore, few
      studies empirically test the operationalization of women's empowerment and
      incorporate multidimensional measures to represent the potentially disparate
      influence of women's status and empowerment on SBA use across settings. METHODS:
      This study examined the relationship of women's status and empowerment with SBA
      use in two African countries--Senegal and Tanzania--using the 2010 Demographic
      and Health Surveys (weighted births n = 10,688 in SN; 6748 in TZ). Factor
      analysis was first conducted to identify the structure and multiple dimensions of
      empowerment. Then, a multivariate regression analysis was conducted to examine
      associations between these empowerment dimensions and SBA use. RESULTS: Overall,
      women's status and empowerment were positively related to SBA use. Some
      sociodemographic characteristics showed similar effects across countries (e.g.,
      age, wealth, residence, marital relationship, parity); however, women's status
      and empowerment influence SBA use differently by setting. Namely, women's
      education directly and positively influenced SBA use in Tanzania, but not in
      Senegal. Further, each of the dimensions of empowerment influenced SBA use in
      disparate ways. In Tanzania women's higher household decision-making power and
      employment were related to SBA use, while in Senegal more progressive perceptions
      of gender norms and older age at first marriage were related to SBA use.
      CONCLUSIONS: This study provides evidence of the disparate influences of women's
      status and empowerment on SBA use across settings. Results indicate that efforts
      to increase SBA use and to reduce maternal mortality through the improvement of
      women's status and empowerment should focus both on improving girls' education
      and delaying marriage, as well as transforming gender norms and decision-making
      power. However, given the multi-dimensional and contextual nature of women's
      status and empowerment, it is critical to identify key drivers to increase SBA
      use in a given setting for contextually tailored policy and programming.

PMID- 26205513
TI  - Nimesulide-loaded nanoparticles for the potential coadjuvant treatment of
      prostate cancer.
AB  - Nimesulide (NS)-loaded nanoparticles (NPNS) were prepared from polylactide-co
      glycolide (PLGA) and eventually coated with chitosan (NPNSCS). Nanoparticles (NP)
      were spherical with sizes 379 +/- 59 nm for NPNS and 393 +/- 66 nm for NPNSCS and
      zeta potentials of -15 +/- 3 mV for NPNS to 10 +/- 4 mV for NPNSCS, suggesting an
      efficient coating. Drug encapsulation rate was high (88 +/- 5% and 83 +/- 7% of
      added drug) for NPNS and NPNSCS, respectively. After NP washing and re
      suspension, 98 +/- 2% and 99 +/- 1% of the drug initially entrapped remained
      associated to NP. NS was dispersed in amorphous state within the polymeric
      matrix. Two-fold dilution of NP with pH 7.4 PBS provoked no drug release.
      However, 30-40% NS was released after a 1/10 dilution. NPNSCS and NPNS diluted
      1/100 reduced the encapsulated drug to around 30% and 70%, respectively. In
      contrast, 100% NS was released from NP under sink conditions in less than 2h. The
      permeability of free-NS (1-1.5 * 10(-5)cm/s) was compared with NPNS (NPNS = 6.4
      8.1 * 10(-6)cm/s and NPNSCS = 5.5-7.0 * 10(-6)cm/s) using the PAMPA assay. The
      cytotoxicity of free-NS and NS in NP on model prostate cancer cells PC-3 and DU
      145 showed the highest cytotoxic effect with NPNSCS on PC-3 cells (IC50 = 89
      MUM).

PMID- 26205514
TI  - Zonisamide: Review of Recent Clinical Evidence for Treatment of Epilepsy.
AB  - Zonisamide is an orally administered antiepileptic drug that was first approved
      for clinical use in Japan in 1989. Since then, it has been licensed in Korea for
      a broad spectrum of epilepsies in adults and children, and in the USA for
      adjunctive therapy of adults with partial seizures, and in Europe for monotherapy
      of adults with newly diagnosed partial seizures and adjunctive therapy of adults
      and adolescents and children aged >=6 years with partial seizures with or without
      secondary generalization. Zonisamide is a benzisoxazole derivative with a unique
      chemical structure, predictable dose-dependent pharmacokinetics, and multiple
      complementary mechanisms of action. Treatment with zonisamide is well tolerated
      and is not known to be associated with clinically significant drug-drug
      interactions, including with oral contraceptives or other antiepileptic drugs.
      There have been >2 million patient-years of experience with zonisamide for
      treatment of epilepsy, and this drug has International League Against Epilepsy
      level A evidence for efficacy/effectiveness as initial monotherapy for adults
      with partial-onset seizures. This review presents the evidence for zonisamide
      across the spectrum of epilepsy, with emphasis on real-world clinical practice
      and special populations of patients (children, elderly patients, and women of
      childbearing age) who are likely to be treated in daily clinical practice.

PMID- 26205515
TI  - Lambs immunized with an inactivated variant of Anaplasma phagocytophilum.
AB  - BACKGROUND: Anaplasma phagocytophilum (formerly Ehrlichia phagocytophila) is an
      obligate intracellular bacterium causing the disease tick-borne fever (TBF) in
      domestic ruminants. An effective vaccine against the infection has been demanded
      for livestock by sheep farmers and veterinary practitioners for years. FINDINGS:
      In the present study, we immunized lambs with an inactivated suspension of 1 *
      10(8) killed A. phagocytophilum organisms mixed with adjuvant (Montanide ISA
      61VG; Seppic). Twelve 9-months-old lambs of the Norwegian White Sheep breed were
      used. A full two-dose series of immunization was given subcutaneously to six
      lambs with a 4 week interval between injections. One month after the last
      immunization, all lambs were challenged with the homologous viable variant of A.
      phagocytophilum. After challenge, all lambs showed clinical responses for several
      days, although the immunized lambs reacted with an anamnestic response, i.e.
      significant reduction in infection rate and a significantly higher antibody
      titer. CONCLUSION: Immunization with inactivated A. phagocytophilum did not
      protect lambs TBF.

PMID- 26205516
TI  - Influence of Antiplatelet Drugs on the Outcome of Subarachnoid Hemorrhage Differs
      with Age.
AB  - BACKGROUND: The aim of this study was to examine the risk factor profiles and
      functional outcomes of subarachnoid hemorrhage (SAH) in different age groups,
      focusing on the effect of antiplatelet drugs when used before stroke. METHODS: A
      total of 5344 patients with SAH were included in a multicenter, hospital-based
      registration study involving 95 Japanese institutes from 2000 to 2012. Patients'
      profiles and use of antithrombotic agents were retrospectively reviewed. A
      modified Rankin Scale score of 4 or more at discharge was defined as poor
      outcome. RESULTS: The frequency of antithrombotic agent use increased with age;
      it reached its peak (10.9%) among patients in their 80s and remained constant at
      7.5% for those 90 years or older. Poorer outcomes were evident as age increased.
      The frequency of hypertension increased with age, whereas current smoking and
      heavy drinking reached its peak among patients in their 40s and 50s,
      respectively. The use of antiplatelet agents significantly improved outcome in
      patients younger than 60 years (P = .04). In contrast, in the older group (>=60
      years), the use of antiplatelet agents tended to worsen the outcome; patients
      aged 70-79 years who had used these agents had a significantly worse outcome
      compared with those who had not (P = .03). CONCLUSIONS: In the present study, the
      influence of antiplatelet agents was different among age groups. The potential
      beneficial effects of antiplatelet agents must be weighed against their potential
      adverse effects in the context of SAH, considering the differences in age-related
      outcomes.

PMID- 26205517
TI  - Stewart-Treves Syndrome of the Breast after Quadrantectomy for Breast Carcinoma.

PMID- 26205518
TI  - Immunogenicity and protective efficacy of Salmonella enterica serovar Pullorum
      pathogenicity island 2 mutant as a live attenuated vaccine candidate.
AB  - BACKGROUND: Salmonella enterica serovar Pullorum (S. Pullorum) causes Pullorum
      disease (PD), a severe systemic disease of poultry and results in considerable
      economic losses in developing countries. In order to develop a safe and
      immunogenic vaccine, the immunogenicity and protective efficacy of
      S06004DeltaSPI2, a Salmonella pathogenicity island 2 (SPI2) deleted mutant of S.
      Pullorum was evaluated in 2-day old chickens. RESULTS: Single intramuscular
      vaccination with S06004DeltaSPI2 (2 * 10(7) CFU) of chickens revealed no
      differences in body weight or clinical symptoms compared to control group.
      S06004DeltaSPI2 bacteria can colonize and persistent in liver and spleen of
      vaccinated chickens approximately 14 days, and specific humoral and cellular
      immune responses were significantly induced. Vaccination of chickens offered
      efficient protection against S. Pullorum strain S06004 and S. Gallinarum strain
      SG9 challenge, respectively, at 10 days post vaccination (dpv) based on mortality
      and clinical symptoms compared to control group. CONCLUSIONS: These findings
      suggest that S06004DeltaSPI2 appears to be a highly immunogenic and efficient
      live attenuated vaccine candidate.

PMID- 26205519
TI  - Altering small and medium alcohol selectivity in the wax ester synthase.
AB  - The bifunctional wax ester synthase/acyl-coenzyme A:diacylglycerol
      acyltransferase (WS/DGAT or wax ester synthase) catalyzes the terminal reaction
      in the bacterial wax ester biosynthetic pathway, utilizing a range of alcohols
      and fatty acyl-CoAs to synthesize the corresponding wax ester. The wild-type wax
      ester synthase Maqu_0168 from Marinobacter aquaeolei VT8 exhibits a preference
      for longer fatty alcohols, while applications with smaller alcohols would yield
      products with desired biotechnological properties. Small and medium chain length
      alcohol substrates are much poorer substrates for the native enzyme, which may
      hinder broad application of the wax ester synthase in many proposed biosynthetic
      schemes. Developing approaches to improve enzyme activity toward specific smaller
      alcohol substrates first requires a clear understanding of which amino acids of
      the primary sequences of these enzymes contribute to substrate specificity in the
      native enzyme. In this report, we surveyed a range of potential residues and
      identified the leucine at position 356 and methionine at position 405 in
      Maqu_0168 as residues that affected selectivity toward small, branched, and
      aromatic alcohols when substituted with different amino acids. This analysis
      provides evidence of residues that line the binding site for wax ester synthase,
      which will aid rational approaches to improve this enzyme with specific
      substrates.

PMID- 26205520
TI  - Proteome signatures--how are they obtained and what do they teach us?
AB  - The dawn of a new Proteomics era, just over a decade ago, allowed for large-scale
      protein profiling studies that have been applied in the identification of
      distinctive molecular cell signatures. Proteomics provides a powerful approach
      for identifying and studying these multiple molecular markers in a vast array of
      biological systems, whether focusing on basic biological research, diagnosis,
      therapeutics, or systems biology. This is a continuously expanding field that
      relies on the combination of different methodologies and current advances, both
      technological and analytical, which have led to an explosion of protein
      signatures and biomarker candidates. But how are these biological markers
      obtained? And, most importantly, what can we learn from them? Herein, we briefly
      overview the currently available approaches for obtaining relevant information at
      the proteome level, while noting the current and future roles of both traditional
      and modern proteomics. Moreover, we provide some considerations on how the
      development of powerful and robust bioinformatics tools will greatly benefit high
      throughput proteomics. Such strategies are of the utmost importance in the
      rapidly emerging field of immunoproteomics, which may play a key role in the
      identification of antigens with diagnostic and/or therapeutic potential and in
      the development of new vaccines. Finally, we consider the present limitations in
      the discovery of new signatures and biomarkers and speculate on how such hurdles
      may be overcome, while also offering a prospect for the next few years in what
      could be one of the most significant strategies in translational medicine
      research. 

PMID- 26205521
TI  - Metabolic engineering of Escherichia coli for production of biodiesel from fatty
      alcohols and acetyl-CoA.
AB  - Microbial production of biodiesel from renewable feedstock has attracted
      intensive attention. Biodiesel is known to be produced from short-chain alcohols
      and fatty acyl-CoAs through the expression of wax ester synthase/fatty acyl-CoA:
      diacylglycerol acyltransferase that catalyzes the esterification of short-chain
      alcohols and fatty acyl-CoAs. Here, we engineered Escherichia coli to produce
      various fatty alcohol acetate esters, which depend on the expression of
      Saccharomyces cerevisiae alcohol acetyltransferase ATF1 that catalyzes the
      esterification of fatty alcohols and acetyl-CoA. The fatty acid biosynthetic
      pathways generate fatty acyl-ACPs, fatty acyl-CoAs, or fatty acids, which can be
      converted to fatty alcohols by fatty acyl-CoA reductase, fatty acyl-ACP
      reductase, or carboxylic acid reductase, respectively. This study showed the
      biosynthesis of biodiesel from three fatty acid biosynthetic pathway
      intermediates. 

PMID- 26205522
TI  - Imidase catalyzing desymmetric imide hydrolysis forming optically active 3
      substituted glutaric acid monoamides for the synthesis of gamma-aminobutyric acid
      (GABA) analogs.
AB  - The recent use of optically active 3-substituted gamma-aminobutyric acid (GABA)
      analogs in human therapeutics has identified a need for an efficient,
      stereoselective method of their synthesis. Here, bacterial strains were screened
      for enzymes capable of stereospecific hydrolysis of 3-substituted glutarimides to
      generate (R)-3-substituted glutaric acid monoamides. The bacteria Alcaligenes
      faecalis NBRC13111 and Burkholderia phytofirmans DSM17436 were discovered to
      hydrolyze 3-(4-chlorophenyl) glutarimide (CGI) to (R)-3-(4-chlorophenyl) glutaric
      acid monoamide (CGM) with 98.1% enantiomeric excess (e.e.) and 97.5% e.e.,
      respectively. B. phytofirmans DSM17436 could also hydrolyze 3-isobutyl
      glutarimide (IBI) to produce (R)-3-isobutyl glutaric acid monoamide (IBM) with
      94.9% e.e. BpIH, an imidase, was purified from B. phytofirmans DSM17436 and found
      to generate (R)-CGM from CGI with specific activity of 0.95 U/mg. The amino acid
      sequence of BpIH had a 75% sequence identity to that of allantoinase from A.
      faecalis NBRC13111 (AfIH). The purified recombinant BpIH and AfIH catalyzed (R)
      selective hydrolysis of CGI and IBI. In addition, a preliminary investigation of
      the enzymatic properties of BpIH and AfIH revealed that both enzymes were stable
      in the range of pH 6-10, with an optimal pH of 9.0, stable at temperatures below
      40  degrees C, and were not metalloproteins. These results indicate that the use
      of this class of hydrolase to generate optically active 3-substituted glutaric
      acid monoamide could simplify the production of specific chiral GABA analogs for
      drug therapeutics.

PMID- 26205523
TI  - A multiplex oligonucleotide ligation-PCR as a complementary tool for subtyping of
      Salmonella Typhimurium.
AB  - Subtyping below the serovar level is essential for surveillance and outbreak
      detection and investigation of Salmonella enterica subsp. enterica serovar
      Typhimurium (S. Typhimurium) and its monophasic variant 1,4,[5],12:i:- (S.
      1,4,[5],12:i:-), frequent causes of foodborne infections. In an attempt to
      overcome the intrinsic shortcomings of currently used subtyping techniques, a
      multiplex oligonucleotide ligation-PCR (MOL-PCR) assay was developed which
      combines different types of molecular markers in a high-throughput microsphere
      suspension array. The 52 molecular markers include prophage genes, amplified
      fragment length polymorphism (AFLP) elements, Salmonella genomic island 1 (SGI1),
      allantoinase gene allB, MLVA locus STTR10, antibiotic resistance genes, single
      nucleotide polymorphisms (SNPs) and phase 2 flagellar gene fljB. The in vitro
      stability of these markers was confirmed in a serial passage experiment. The
      validation of the MOL-PCR assay for subtyping of S. Typhimurium and S.
      1,4,[5],12:i:- on 519 isolates shows that the method is rapid, reproducible,
      flexible, accessible, easy to use and relatively inexpensive. Additionally, a 100
      % typeability and a discriminatory power equivalent to that of phage typing were
      observed, and epidemiological concordance was assessed on isolates of 2 different
      outbreaks. Furthermore, a data analysis method is provided so that the MOL-PCR
      assay allows for objective, computerised data analysis and data interpretation of
      which the results can be easily exchanged between different laboratories in an
      international surveillance network.

PMID- 26205524
TI  - Comparison of Arthrodesis with Total Contact Casting for Midfoot Ulcerations
      Associated with Charcot Neuroarthropathy.
AB  - BACKGROUND: Gross deformity of the foot in Charcot neuroarthropathy can lead to
      foot collapse and subsequent ulceration, infection, amputation, or premature
      death. Total-contact casting (TCC) is a well-established treatment for
      neuropathic diabetic plantar foot ulcers. It was hypothesized that arthrodesis
      plus TCC may have advantages over TCC alone. This pilot study compared the
      effectiveness of arthrodesis plus TCC with TCC alone for the prevention,
      treatment, and recurrence of midfoot ulcerations associated with Charcot
      neuroarthropathy. MATERIAL AND METHODS: Twenty-one subjects with plantar ulcers
      associated with unilateral diabetic Charcot midfoot neuroarthropathy were
      randomly assigned to ADS or TCC groups. The ADS group underwent an extended
      medial column arthrodesis procedure and TCC; ulcers were sutured directly. The
      TCC group underwent TCC alone with dressing changes. All patients underwent nerve
      conduction studies and quantitative sensory testing at baseline and during follow
      up (6 and 12 months). Healing time and ulcer relapse rate were evaluated.
      RESULTS: Compared with the TCC group, there were fewer lesions in the ADS group
      after treatment (P<0.05). Temperature testing and vibration perception threshold
      improved significantly after ADS (P<0.05). Although the number of patients
      positive for pinprick and light touch sensations increased after surgery, not all
      patients recovered these sensations. Healing time was not significantly different
      between the 2 groups (24.25+/-3.89 vs. 25.89+/-2.84 days, P>0.05). There was no
      ulcer recurrence after 12 months in the ADS group compared with 33.3% in the TCC
      group. CONCLUSIONS: An extended medial column arthrodesis may partly improve
      sensory impairments and restore protective sensation in patients with Charcot
      neuroarthropathy.

PMID- 26205525
TI  - Two cases of pineal-region meningiomas derived from arachnoid membrane over the
      vein of Galen without dural attachment.
AB  - BACKGROUND: We present two rare cases of pineal-region meningiomas. These tumors
      are the first reported cases of dura-unrelated meningiomas originating from the
      arachnoid membrane over the vein of Galen (AMG). CASE DESCRIPTION: In Case 1, a
      37-year-old woman presented with a progressing headache. Magnetic resonance
      imaging (MRI) showed a large tumor in the pineal region, displacing the vein of
      Galen upward. Angiography disclosed occlusion of the vein of Galen, with deep
      venous flow draining through the veins on the right medial surface of the
      occipital lobe to the superior sagittal sinus. In Case 2, a 67-year-old man
      presented with dizziness. MRI demonstrated a large mass in the pineal region,
      displacing the vein of Galen inferiorly. Angiography disclosed occlusion of the
      vein of Galen, with deep venous flow draining through the collateral venous
      channel into the transverse sinus. Both tumors were totally excised (Simpson
      Grade III for Case 1, Grade I for Case 2) via a left occipital transtentorial
      approach. No dural attachment was recognized in either case, but the tumor in
      Case 1 was firmly adherent to the inferior portion of the AMG, while that in Case
      2 was attached to the superior portion of the AMG, but remained dissectible.
      CONCLUSIONS: We reported two cases of pineal-region meningiomas originating from
      the arachnoid membrane over the vein of Galen, resulting in meningioma without
      dural attachment. These tumors can be totally resected by careful dissection of
      the tumor from the arachnoid membrane surrounding the vein of Galen.

PMID- 26205526
TI  - Natural selection on plant resistance to herbivores in the native and introduced
      range.
AB  - When plants are introduced into new regions, the absence of their co-evolved
      natural enemies can result in lower levels of attack. As a consequence of this
      reduction in enemy pressure, plant performance may increase and selection for
      resistance to enemies may decrease. In the present study, we compared leaf
      damage, plant size and leaf trichome density, as well as the direction and
      magnitude of selection on resistance and plant size between non-native (Spain)
      and native (Mexico) populations of Datura stramonium. This species was introduced
      to Spain about five centuries ago and constitutes an ideal system to test four
      predictions of the enemy release hypothesis. Compared with native populations, we
      expected Spanish populations of D. stramonium to have (i) lower levels of foliar
      damage; (ii) larger plant size; (iii) lower leaf trichome density that is
      unrelated to foliar damage by herbivores; and (iv) weak or no selection on
      resistance to herbivores but strong selection on plant size. Our results showed
      that, on average, plants from non-native populations were significantly less
      damaged by herbivores, were less pubescent and were larger than those from native
      populations. We also detected different selection regimes on resistance and plant
      size between the non-native and native ranges. Positive selection on plant size
      was detected in both ranges (though it was higher in the non-native area), but
      consistent positive selection on relative resistance was detected only in the
      native range. Overall, we suggest that changes in selection pressure on
      resistance and plant size in D. stramonium in Spain are a consequence of 'release
      from natural enemies'. 

PMID- 26205527
TI  - Social challenge increases cortisol and hypothalamic monoamine levels in matrinxa
      (Brycon amazonicus).
AB  - The neural circuitry for social behavior and aggression appears to be
      evolutionarily conserved across the vertebrate subphylum and involves a complex
      neural network that includes the hypothalamus as a key structure. In the present
      study, we evaluated the changes in monoamine levels in the hypothalamus and on
      serum cortisol and plasma glucose of resident matrinxa (Brycon amazonicus)
      submitted to a social challenge (introduction of an intruder in their territory).
      The fight promoted a significant increase in hypothalamic 5-HT, NA and DA levels
      and on the metabolites 5-HIAA and DOPAC, and decreased 5-HIAA/5-HT and DOPAC/DA
      ratios in resident fish. Furthermore, an increase in serum cortisol and plasma
      glucose was also observed after the fight. Resident fish presented a high
      aggressiveness even with increased 5-HT levels in the hypothalamus. The
      alteration in hypothalamic monoaminergic activity of matrinxa suggests that this
      diencephalic region is involved in aggression and stress modulation in fish;
      however, it does not exclude the participation of other brain areas not tested
      here. 

PMID- 26205528
TI  - Comparative analysis on natural spawning of F1 meagre, Argyrosomus regius, with
      wild broodstock spawns in Portugal.
AB  - The purpose of this study was to describe and compare the reproductive success
      and egg and larvae quality between wild and first-generation (F1) breeders of
      Argyrosomus regius. Wild broodstock were adapted to captivity, and good-quality
      spawns were obtained in 2009-2010, after GnRH treatment. In 2012, the F1 meagre
      (3 years old) spawned naturally at IPMA's Aquaculture Research Station
      facilities. From each spawning event, the following parameters were determined:
      number of floating and non-floating eggs, egg size, hatching success and larval
      total length. Eggs size and percentage of hatching obtained from F1 breeders
      (1.04 +/- 0.10 mm and 90.5 +/- 6.4%) were significantly higher when compared with
      wild breeders (0.97 +/- 0.13 mm and 17.0 +/- 12.7%). Although wild breeder spawns
      exhibited 2.7 +/- 0.2 mm for larval total length, F1 breeder spawns presented 2.6
      +/- 0.2 mm. The wild and F1 breeder spawns exhibit a good egg and larval quality,
      indicating a promising starting point for a successful meagre hatchery
      production.

PMID- 26205529
TI  - Complete loss of the DNAJB6 G/F domain and novel missense mutations cause distal
      onset DNAJB6 myopathy.
AB  - INTRODUCTION: Protein aggregation is a common cause of neuropathology. The
      protein aggregation myopathy Limb-Girdle Muscular Dystrophy 1D (LGMD1D) is caused
      by mutations of amino acids Phe89 or Phe93 of DNAJB6, a co-chaperone of the HSP70
      anti-aggregation protein. Another DNAJB6 mutation, Pro96Arg, was found to cause a
      distal-onset myopathy in one family. RESULTS: We detail the mutational,
      neuropathological, neurophysiological, neurological and radiological features of
      five new DNAJB6-myopathy families. One has the known Phe93Leu mutation and
      classic late-onset slowly progressive LGMD1D. Two have different mutations of
      Phe91 causing a variant childhood-onset severe limb-girdle myopathy. One has a
      Phe100Val mutation and distal-onset myopathy, unique early bulbar involvement,
      and a gender-modified wide age-of-onset range. The last has childhood-onset
      severe distal-onset myopathy and the first non-missense DNAJB6 mutation, c.346 +
      5G > A, causing a splicing defect that entirely eliminates DNAJB6's G/F domain
      (DeltaG/F), the domain that harbours all other mutations. Clinical and imaging
      examinations reveal that muscles considered uninvolved in DNAJB6-myopathy, e.g.
      lateral gastrocnemii, are affected in our patients with new mutations. Mutational
      modelling based on the known structure of the bacterial DNAJ2 protein indicates
      that all past and present mutated residues cluster within 15 A in the G/F domain
      and all disturb the interface of this domain with the protein's J domain that
      confers the interaction with HSP70. CONCLUSIONS: Our patients expand the
      phenotypic spectrum of DNAJB6-myopathy and allow tentative genotype-phenotype
      specifications. Combining with previous studies, the clinical severity spectrum
      is as follows: DeltaG/F and Phe91 mutations, most severe; Phe100, Pro96, Phe89
      mutations, intermediate; and Phe93, least severe. As it stands presently,
      proximal G/F domain mutations (Phe89, Phe91, Phe93) cause proximal limb-girdle
      myopathy, while distal G/F mutations (Pro96, Phe100) cause distal-onset myopathy.
      While all mutations affect the G/F-J interaction, each likely does so in
      different unknown extents or ways. One mutation, DeltaG/F, causes its associated
      severe distal-onset myopathy phenotype in a clear way, through generation of a
      G/F domain-lacking DNAJB6 protein.

PMID- 26205530
TI  - Establishment of a new animal model of azithromycin-induced liver injury and
      study the molecular pathological change during the process.
AB  - The purpose of the present study is to establish a new animal model of
      azithromycin (AZ)-induced liver injury and study the molecular pathological
      change during the process. First, mice were respectively injected
      intraperitoneally with AZ of different high doses. Our results showed that 800
      mg/kg AZ injection significantly induced liver injury in the mice, which
      reflected an ideal process of liver injury and repair. In this study, we analyzed
      the molecular pathological changes during the process by hematoxylin and eosin
      staining, immunohistochemistry, Western blot, and quantitative real-time reverse
      transcription polymerase chain reaction in the liver of mice at 0, 12, 24, 48,
      and 72 h after 800 mg/kg injection. Our results showed that the expression of
      heat shock protein 70, proliferating cell nuclear antigen, vascular endothelial
      growth factor, caspase 3, and cytochrome P450 2E1 were significantly differently
      expressed during liver injury induced by 800 mg/kg AZ in mice. Our results will
      be conducive for further study of the pathogenesis and prevention of drug-induced
      liver injury. 

PMID- 26205531
TI  - A Multi-Institutional Analysis of Outcomes of Patients with Clinically Node
      Positive Urothelial Bladder Cancer Treated with Induction Chemotherapy and
      Radical Cystectomy.
AB  - PURPOSE: Selected patients with bladder cancer with pelvic lymphadenopathy (cN1
      3) are treated with induction chemotherapy followed by radical cystectomy.
      However, the data on clinical outcomes in these patients are limited. In this
      study we assess pathological and survival outcomes in patients with cN1-3 disease
      treated with induction chemotherapy and radical cystectomy. MATERIALS AND
      METHODS: Data were collected on patients from 19 North American and European
      centers with cT1-4aN1-N3 urothelial carcinoma who received chemotherapy followed
      by radical cystectomy between 2000 and 2013. The primary end points were
      pathological complete (pT0N0) and partial (pT1N0 or less) response rates, with
      overall survival as a secondary end point. Logistic regression and Cox
      proportional hazard ratios were used for multivariate analysis of factors
      predicting these outcomes. RESULTS: The total of 304 patients had clinical
      evidence of lymph node involvement (cN1-N3).
      Methotrexate/vinblastine/doxorubicin/cisplatin was used in 128 (42%),
      gemcitabine/cisplatin in 132 (43%) and other regimens in 44 (15%) patients. The
      pN0 rate was 48% (cN1-56%, cN2-39%, cN3-39%, p=0.03). The complete and partial
      pathological response rates for the entire cohort were 14.5% and 27%,
      respectively. The estimated median overall survival time for the cohort was 22
      months (IQR 8.0, 54). On Cox regression analysis overall survival was associated
      with pN0, negative surgical margins, removal of 15 or more pelvic nodes and
      cisplatin therapy. CONCLUSIONS: Complete pathological nodal response can be
      achieved in a proportion of patients with cN1-3 disease receiving induction
      chemotherapy. The best survival outcomes are observed in male patients on
      cisplatin regimens with subsequent negative radical cystectomy margins and
      complete nodal response (pN0) with excision of 15 or more pelvic nodes.

PMID- 26205532
TI  - Accurate contact predictions using covariation techniques and machine learning.
AB  - Here we present the results of residue-residue contact predictions achieved in
      CASP11 by the CONSIP2 server, which is based around our MetaPSICOV contact
      prediction method. On a set of 40 target domains with a median family size of
      around 40 effective sequences, our server achieved an average top-L/5 long-range
      contact precision of 27%. MetaPSICOV method bases on a combination of classical
      contact prediction features, enhanced with three distinct covariation methods
      embedded in a two-stage neural network predictor. Some unique features of our
      approach are (1) the tuning between the classical and covariation features
      depending on the depth of the input alignment and (2) a hybrid approach to
      generate deepest possible multiple-sequence alignments by combining jackHMMer and
      HHblits. We discuss the CONSIP2 pipeline, our results and show that where the
      method underperformed, the major factor was relying on a fixed set of parameters
      for the initial sequence alignments and not attempting to perform domain
      splitting as a preprocessing step. Proteins 2016; 84(Suppl 1):145-151. (c) 2015
      The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley
      Periodicals, Inc.

PMID- 26205533
TI  - Clinical characteristics and outcome of clinically diagnosed viral encephalitis
      in southwest China.
AB  - Patients with viral encephalitis have a high incidence of morbidity and
      mortality. We analyze the clinical characteristics and outcome of patients with
      clinically diagnosed viral encephalitis to investigate possible predictors of
      prognosis. We retrospectively evaluated 1107 patients diagnosed with viral
      encephalitis in southwest China from 2009 to 2012 by evaluating their outcomes
      using the Glasgow Outcome Scale. We compared patient outcome at hospital
      discharge with long-term follow-up visits, and evaluated the prognostic
      indicators of the outcome. At hospital discharge, 375 (33.9 %) of the 1107
      patients who survived made a full recovery, while 399 (36.0 %), 160 (14.5 %), and
      145 (13.1 %) had mild, moderate or severe neurologic sequelae, respectively.
      Twenty-eight (2.5 %) of the patients died prior to discharge from the hospital.
      Of the 1027 patients who had follow-up assessments, 658 (64.1 %) made a full
      recovery, while 213 (20.7 %), 103 (10.0 %), and 19 (1.8 %) had mild, moderate or
      severe neurologic sequelae, respectively. Six (0.6 %) of the patients died after
      discharge from the hospital. Use of mechanical ventilation, lower Glasgow coma
      score, and concurrent seizures are predictors for a poor outcome in patients both
      at hospital discharge and at long-term follow-up visits.

PMID- 26205534
TI  - The diagnostic and prognostic value of serum CXCL12 levels in patients with
      ischemic stroke.
AB  - The aim of this study was to investigate the potential diagnostic and prognostic
      role of CXC chemokine ligand-12 (CXCL12) in Chinese patients with acute ischemic
      stroke (AIS). All consecutive patients with first-ever AIS from January 2014 to
      August 2014 were recruited to participate in the study. CXCL12 and NIH Stroke
      Scale were measured at the time of admission. Short-term functional outcome was
      measured by modified Rankin scale 3 months after admission. Multivariate analyses
      were performed using logistic regression models. Receiver operating
      characteristic (ROC) curve was used to evaluate the accuracy of serum CXCL12 in
      diagnosing stroke and prognosing functional outcome. From 375 screened patients,
      a total of 288 patients with first-ever AIS were included in this study. Based on
      the ROC curve, the optimal cutoff value of serum CXCL12 levels as an indicator
      for auxiliary diagnosis of AIS was projected to be 3.5 ng/mL, which yielded a
      sensitivity of 88.1 % and a specificity of 73.5 %, with the area under the curve
      at 0.907 (95 % CI 0.882-0.932). In multivariate analysis, there was an increased
      risk of unfavorable outcome associated with serum CXCL12 levels >=7.6 ng/mL (OR
      4.356, 95 % CI 2.993-7.132, P < 0.0001) after adjusting for possible confounders.
      Our study demonstrated that elevated serum CXCL12 level at admission was an
      independent diagnostic and prognostic marker in patients with AIS.

PMID- 26205536
TI  - Further characterisation of transmissible spongiform encephalopathy phenotypes
      after inoculation of cattle with two temporally separated sources of sheep
      scrapie from Great Britain.
AB  - BACKGROUND: The infectious agent responsible for the bovine spongiform
      encephalopathy (BSE) epidemic in Great Britain is a transmissible spongiform
      encephalopathy (TSE) strain with uniform properties but the origin of this strain
      remains unknown. Based on the hypothesis that classical BSE may have been caused
      by a TSE strain present in sheep, cattle were inoculated intracerebrally with two
      different pools of brains from scrapie-affected sheep sourced prior to and during
      the BSE epidemic to investigate resulting disease phenotypes and characterise
      their causal agents by transmission to rodents. RESULTS: As reported in 2006,
      intracerebral inoculation of cattle with pre-1975 and post-1990 scrapie brain
      pools produced two distinct disease phenotypes, which were unlike classical BSE.
      Subsequent to that report none of the remaining cattle, culled at 10 years post
      inoculation, developed a TSE. Retrospective Western immunoblot examination of the
      brains from TSE cases inoculated with the pre-1975 scrapie pool revealed a
      molecular profile similar to L-type BSE. The inoculation of transgenic mice
      expressing the bovine, ovine, porcine, murine or human prion protein gene and
      bank voles with brains from scrapie-affected cattle did not detect classical or
      atypical BSE strains but identified two previously characterised scrapie strains
      of sheep. CONCLUSIONS: Characterisation of the causal agents of disease resulting
      from exposure of cattle to naturally occurring scrapie agents sourced in Great
      Britain did not reveal evidence of classical or atypical BSE, but did identify
      two distinct previously recognised strains of scrapie. Although scrapie was still
      recognizable upon cattle passage there were irreconcilable discrepancies between
      the results of biological strain typing approaches and molecular profiling
      methods, suggesting that the latter may not be appropriate for the identification
      and differentiation of atypical, particularly L-type, BSE agents from cattle
      experimentally infected with a potential mixture of classical scrapie strains
      from sheep sources.

PMID- 26205537
TI  - Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in
      humanized mice.
AB  - Experimental studies of Plasmodium parasites that infect humans are restricted by
      their host specificity. Humanized mice offer a means to overcome this and further
      provide the opportunity to observe the parasites in vivo. Here we improve on
      previous protocols to achieve efficient double engraftment of TK-NOG mice by
      human primary hepatocytes and red blood cells. Thus, we obtain the complete
      hepatic development of P. falciparum, the transition to the erythrocytic stages,
      their subsequent multiplication, and the appearance of mature gametocytes over an
      extended period of observation. Furthermore, using sporozoites derived from two
      P. ovale-infected patients, we show that human hepatocytes engrafted in TK-NOG
      mice sustain maturation of the liver stages, and the presence of late-developing
      schizonts indicate the eventual activation of quiescent parasites. Thus, TK-NOG
      mice are highly suited for in vivo observations on the Plasmodium species of
      humans. 

PMID- 26205535
TI  - Heterogeneity in ALSFRS-R decline and survival: a population-based study in
      Italy.
AB  - Very few studies examined trend over time of the revised Amyotrophic Lateral
      Sclerosis Functional Rating Scale (ALSFRS-R) and factors influencing it; previous
      studies, then, included only patients attending tertiary ALS Centres. We studied
      ALSFRS-R decline, factors influencing this trend and survival in a population
      based setting. From 2009 onwards, a prospective registry records all incident ALS
      cases among residents in Emilia Romagna (population: 4.4 million). For each
      patient, demographic and clinical details (including ALSFRS-R) are collected by
      caring physicians at each follow-up. Analysis was performed on 402 incident cases
      (1279 ALSFRS-R assessments). The average decline of the ALSFRS-R was 0.60
      points/month during the first year after diagnosis and 0.34 points/month in the
      second year. ALSFRS-R decline was heterogeneous among subgroups. Repeated
      measures mixed model showed that ALSFRS-R score decline was influenced by age at
      onset (p < 0.01), phenotype (p = 0.01), body mass index (BMI) (p < 0.01),
      progression rate at diagnosis (DeltaFS) (p < 0.01), El Escorial Criteria-Revised
      (p < 0.01), and FVC% at diagnosis (p < 0.01). Among these factors, at
      multivariate analysis, only age, site of onset and DeltaFS independently
      influenced survival. In this first population-based study on ALSFRS-R trend, we
      confirm that ALSFRS-R decline is not homogeneous among ALS patients and during
      the disease. Factors influencing ALSFRS-R decline may not match with those
      affecting survival. These disease modifiers should be taken into consideration
      for trials design and in clinical practice during discussions with patients on
      prognosis.

PMID- 26205538
TI  - Synthesis and evaluation in rats of homologous series of [(18)F]-labeled dopamine
      D 2/3 receptor agonists based on the 2-aminomethylchroman scaffold as potential
      PET tracers.
AB  - BACKGROUND: Agonist positron emission tomography (PET) tracers for dopamine D2/3
      receptors (D2/3Rs) offer greater sensitivity to changes in endogenous dopamine
      levels than D2/3R antagonist tracers. D2/3R agonist tracers currently available
      for clinical research are labeled with the short-lived isotope carbon-11, which
      limits their use. We aimed to develop high-affinity D2R agonists amenable for
      labeling with the longer-living fluorine-18. Here, we report the evaluation as
      potential PET tracers of two homologous series of [(18)F]fluorinated tracers
      based on the 2-aminomethylchroman-7-ol (AMC) scaffold: (R)-2-((4-(2
      fluoroalkoxy)benzylamino)methyl)chroman-7-ols (AMC13 homologues) and (R)-2-((2-(4
      (4-(fluoroalkoxy)phenyl)piperazin-1-yl)ethylamino)methyl)chroman-7-ols (AMC15
      homologues). We varied the length of the (18)F-fluoroalkyl chain in these
      structures to balance brain penetration and non-specific binding of the
      radioligands by adjusting their lipophilicity. METHODS: The tracers were
      evaluated in brain slices of Sprague-Dawley rats by in vitro autoradiography and
      in living rats by microPET imaging and ex vivo autoradiography. PET data were
      analyzed with one- and two-tissue compartmental models (1TCM/2TCM), simplified
      reference tissue model (SRTM), and Logan graphical analysis. Specificity of
      binding was tested by blocking D2/3R with raclopride. RESULTS: Homologues with a
      shorter fluoroalkyl chain consistently showed greater D2/3R-specific-to-total
      binding ratios in the striatum than those with longer chains. The fluoroethoxy
      homologue of AMC13 ([(18)F]FEt-AMC13) demonstrated the highest degree of D2/3R
      specific binding among the evaluated tracers: mean striatum-to-cerebellum uptake
      ratio reached 4.4 in vitro and 2.1/2.8 in vivo/ex vivo (PET/autoradiography).
      Striatal binding potential (BPND) relative to cerebellum was 0.51-0.63 depending
      on the estimation method. Radiometabolites of [(18)F]FEt-AMC13 did not enter the
      brain. In vitro, application of 10 MUmol/L raclopride reduced D2/3R-specific
      binding of [(18)F]FEt-AMC13 in the striatum by 81 %. In vivo, pre-treatment with
      1 mg/kg (2.9 MUmol/kg) raclopride led to 17-39 % decrease in D2/3R-specific
      binding in the striatum. CONCLUSIONS: Varying the length of the
      [(18)F]fluoroalkyl chain helped improve the characteristics of the original
      candidate tracers. Further modifications of the current lead [(18)F]FEt-AMC13 can
      provide an agonist radiopharmaceutical suitable for D2/3R imaging by PET.

PMID- 26205539
TI  - Activation of alpha1-adrenoceptors facilitates excitatory inputs to medullary
      airway vagal preganglionic neurons.
AB  - In mammals, the neural control of airway smooth muscle is dominated by a subset
      of airway vagal preganglionic neurons in the ventrolateral medulla. These neurons
      are physiologically modulated by adrenergic/noradrenergic projections, and
      weakened alpha2-adrenergic inhibition of them is indicated to participate in the
      pathogenesis and exacerbation of asthma. This study tests whether these neurons
      are modulated by alpha1-adrenoceptors, and if so, how. In anesthetized adult
      rats, microinjection of the alpha1A-adrenoceptor agonist A61603 (1 pmol)
      unilaterally into the medullary region containing these neurons caused a
      significant increase in airway resistance, which was prevented by intraperitoneal
      atropine (0.5 mg/kg). In rhythmically firing medullary slices of newborn rats,
      A61603 (10 nM) caused depolarization in both the inspiratory-activated and
      inspiratory-inhibited airway vagal preganglionic neurons that were retrogradely
      labeled, and a significant increase in the spontaneous firing rate. Under voltage
      clamp, A61603 significantly enhanced the spontaneous excitatory inputs to both
      types of neurons and caused a tonic inward current in the inspiratory-activated
      neurons along with significantly increased peak amplitude of the inspiratory
      inward currents. The responses in vitro were prevented by alpha1A-adrenoceptor
      antagonist RS100329 (1 MUM), which alone significantly inhibited the spontaneous
      excitatory inputs to both types of the neurons. After pretreatment with
      tetrodotoxin (1 MUM), A61603 (10 or 100 nM) had no effect on either type of
      neuron. We conclude that in rats, activation of alpha1-adrenoceptors in the
      medullary region containing airway vagal preganglionic neurons increases airway
      vagal tone, and that this effect is primarily mediated by facilitation of the
      excitatory inputs to the preganglionic neurons.

PMID- 26205540
TI  - Heat acclimation attenuates physiological strain and the HSP72, but not
      HSP90alpha, mRNA response to acute normobaric hypoxia.
AB  - Heat acclimation (HA) attenuates physiological strain in hot conditions via
      phenotypic and cellular adaptation. The aim of this study was to determine
      whether HA reduced physiological strain, and heat shock protein (HSP) 72 and
      HSP90alpha mRNA responses in acute normobaric hypoxia. Sixteen male participants
      completed ten 90-min sessions of isothermic HA (40 degrees C/40% relative
      humidity) or exercise training [control (CON); 20 degrees C/40% relative
      humidity]. HA or CON were preceded (HYP1) and proceeded (HYP2) by a 30-min
      normobaric hypoxic exposure [inspired O2 fraction = 0.12; 10-min rest, 10-min
      cycling at 40% peak O2 uptake (VO2 peak), 10-min cycling at 65% VO2 peak]. HA
      induced greater rectal temperatures, sweat rate, and heart rates (HR) than CON
      during the training sessions. HA, but not CON, reduced resting rectal
      temperatures and resting HR and increased sweat rate and plasma volume.
      Hemoglobin mass did not change following HA nor CON. HSP72 and HSP90alpha mRNA
      increased in response to each HA session, but did not change with CON. HR during
      HYP2 was lower and O2 saturation higher at 65% VO2 peak following HA, but not
      CON. O2 uptake/HR was greater at rest and 65% VO2 peak in HYP2 following HA, but
      was unchanged after CON. At rest, the respiratory exchange ratio was reduced
      during HYP2 following HA, but not CON. The increase in HSP72 mRNA during HYP1 did
      not occur in HYP2 following HA. In CON, HSP72 mRNA expression was unchanged
      during HYP1 and HYP2. In HA and CON, increases in HSP90alpha mRNA during HYP1
      were maintained in HYP2. HA reduces physiological strain, and the transcription
      of HSP72, but not HSP90alpha mRNA in acute normobaric hypoxia.

PMID- 26205541
TI  - Conditional depletion of methyl-CpG-binding protein 2 in astrocytes depresses the
      hypercapnic ventilatory response in mice.
AB  - Mice that are deficient in the transcription factor methyl-CpG-binding protein 2
      (MeCP2) have a depressed hypercapnic ventilatory response (HCVR). The expression
      of MeCP2 can be selectively removed from astrocytes or neurons, thus offering a
      tool to dissect the role of this transcription factor in astrocytes from that in
      neurons. Studies were carried out in the progeny of mice that were a cross
      between those harboring a tamoxifen (TAM)-inducible Cre recombinase transgene
      driven by the human astrocytic glial fibrillary acidic protein (hGFAP) promoter,
      or Cre recombinase under control of the synapsin promoter, with mice containing a
      Cre-excisable exon III in the Mecp2 gene. The TAM-conditional excision of the
      Mecp2 exon allowed the respiratory CO2 response to be studied in the same animals
      before and after selective depletion of MeCP2 in astrocytes. Immunohistochemistry
      showed that following TAM treatment only ~20% of GFAP-labeled cells in the
      retrotrapazoid nucleus and in the raphe magnus were positive for MeCP2. The slope
      of the relative increase in minute ventilation as a function of 1, 3, and 5%
      inspired CO2 was depressed in mice with depleted astrocyte MeCP2 compared with
      wild-type littermates. In contrast, selective depletion of MeCP2 in neurons did
      not significantly affect slope. While neurons which constitute the respiratory
      network ultimately determine the ventilatory response to CO2, this study
      demonstrates that loss of MeCP2 in astrocytes alone is sufficient to result in a
      dramatic attenuation of the HCVR. We propose that the glial contribution to HCVR
      is under the control of the MeCP2 gene. 

PMID- 26205542
TI  - Pulmonary vascular function and exercise capacity in black sub-Saharan Africans.
AB  - Sex and age affect the pulmonary circulation. Whether there may be racial
      differences in pulmonary vascular function is unknown. Thirty white European
      Caucasian subjects (15 women) and age and body-size matched 30 black sub-Saharan
      African subjects (15 women) underwent a cardiopulmonary exercise test and
      exercise stress echocardiography with measurements of pulmonary artery pressure
      (PAP) and cardiac output (CO). A pulmonary vascular distensibility coefficient
      alpha was mathematically determined from the natural curvilinearity of multipoint
      mean PAP (mPAP)-CO plots. Maximum oxygen uptake (Vo2max) and workload were higher
      in the whites, while maximum respiratory exchange ratio and ventilatory
      equivalents for CO2 were the same. Pulmonary hemodynamics were not different at
      rest. Exercise was associated with a higher maximum total pulmonary vascular
      resistance, steeper mPAP-CO relationships, and lower alpha-coefficients in the
      blacks. These differences were entirely driven by higher slopes of mPAP-CO
      relationships (2.5 +/- 0.7 vs. 1.4 +/- 0.7 mmHg.l(-1).min; P < 0.001) and lower
      alpha-coefficients (0.85 +/- 0.33 vs. 1.35 +/- 0.51%/mmHg; P < 0.01) in black men
      compared with white men. There were no differences in any of the hemodynamic
      variables between black and white women. In men only, the slopes of mPAP-CO
      relationships were inversely correlated to Vo2max (P < 0.01). Thus the pulmonary
      circulation is intrinsically less distensible in black sub-Saharan African men
      compared with white Caucasian Europeans men, and this is associated with a lower
      exercise capacity. This study did not identify racial differences in pulmonary
      vascular function in women. 

PMID- 26205543
TI  - Interactions between breathing rate and low-frequency fluctuations in blood
      pressure and cardiac intervals.
AB  - Evidence derived from spontaneous measures of cardiovagal baroreflex sensitivity
      (BRS) suggests that slow breathing at 6 breaths/min augments BRS. However,
      increases in BRS associated with slow breathing may simply reflect the frequency
      dependent nature of the baroreflex rather than the modulation of baroreflex
      function by changes in breathing rate per se. To test this hypothesis we employed
      a crossover study design (n = 14) wherein breathing rate and systolic arterial
      blood pressure (SAP) oscillation induced via the application of oscillating lower
      body negative pressure (OLBNP) were independently varied at fixed frequencies.
      Breathing rate was controlled at 6 or 10 breaths/min with the aid of a metronome,
      and SAP oscillations were driven at 0.06 Hz and 0.1 Hz using OLBNP. The
      magnitudes of SAP and R-R interval (cardiac period) oscillations were quantified
      using power spectral analysis, and the transfer function gain between SAP and R-R
      interval was used to estimate BRS. Linear mixed-effects models were used to
      examine the main effects and interactions between breathing rate and OLBNP
      frequency. There was no statistical interaction between breathing and OLBNP
      frequency (P = 0.59), indicating that the effect of breathing rate on BRS did not
      differ according to OLBNP frequency (and vice versa). Additionally, there was no
      main effect for breathing rate (P = 0.28). However, we observed a significant
      main effect for OLBNP frequency (P = 0.01) consistent with the frequency
      dependent nature of baroreflex. These findings suggest that increases in spectral
      indices of BRS reflect the frequency dependence of the baroreflex and are not due
      to slow breathing per se. 

PMID- 26205544
TI  - The role of myostatin and activin receptor IIB in the regulation of unloading
      induced myofiber type-specific skeletal muscle atrophy.
AB  - Chronic unloading induces decrements in muscle size and strength. This adaptation
      is governed by a number of molecular factors including myostatin, a potent
      negative regulator of muscle mass. Myostatin must first be secreted into the
      circulation and then bind to the membrane-bound activin receptor IIB (actRIIB) to
      exert its atrophic action. Therefore, we hypothesized that myofiber type-specific
      atrophy observed after hindlimb suspension (HLS) would be related to myofiber
      type-specific expression of myostatin and/or actRIIB. Wistar rats underwent HLS
      for 10 days, after which the tibialis anterior was harvested for frozen cross
      sectioning. Simultaneous multichannel immunofluorescent staining combined with
      differential interference contrast imaging was employed to analyze myofiber type
      specific expression of myostatin and actRIIB and myofiber type cross-sectional
      area (CSA) across fiber types, myonuclei, and satellite cells. Hindlimb
      suspension (HLS) induced significant myofiber type-specific atrophy in myosin
      heavy chain (MHC) IIx (P < 0.05) and MHC IIb myofibers (P < 0.05). Myostatin
      staining associated with myonuclei was less in HLS rats compared with controls,
      while satellite cell staining for myostatin remained unchanged. In contrast, the
      total number myonuclei and satellite cells per myofiber was reduced in HLS
      compared with ambulatory control rats (P < 0.01). Sarcoplasmic actRIIB staining
      differed between myofiber types (I < IIa < IIx < IIb) independent of loading
      conditions. Myofiber types exhibiting the greatest cytoplasmic staining of
      actRIIB corresponded to those exhibiting the greatest degree of atrophy following
      HLS. Our data suggest that differential expression of actRIIB may be responsible
      for myostatin-induced myofiber type-selective atrophy observed during chronic
      unloading. 

PMID- 26205545
TI  - The acute response of pericytes to muscle-damaging eccentric contraction and
      protein supplementation in human skeletal muscle.
AB  - Skeletal muscle pericytes increase in quantity following eccentric exercise (ECC)
      and contribute to myofiber repair and adaptation in mice. The purpose of the
      present investigation was to examine pericyte quantity in response to muscle
      damaging ECC and protein supplementation in human skeletal muscle. Male subjects
      were divided into protein supplement (WHY; n = 12) or isocaloric placebo (CHO; n
      = 12) groups and completed ECC using an isokinetic dynamometer. Supplements were
      consumed 3 times/day throughout the experimental time course. Biopsies were
      collected prior to (PRE) and 3, 24, 48, and 168 h following ECC. Reflective of
      the damaging protocol, integrin subunits, including alpha7, beta1A, and beta1D,
      increased (3.8-fold, 3.6-fold and 3.9-fold, respectively, P < 0.01) 24 h post-ECC
      with no difference between supplements. Pericyte quantity did not change post
      ECC. WHY resulted in a small, but significant, decrease in ALP(+) pericytes when
      expressed as a percentage of myonuclei (CHO 6.8 +/- 0.3% vs. WHY 5.8 +/- 0.3%, P
      < 0.05) or per myofiber (CHO 0.119 +/- 0.01 vs. WHY 0.098 +/- 0.01, P < 0.05).
      The quantity of myonuclei expressing serum response factor and the number of
      pericytes expressing serum response factor, did not differ as a function of time
      post-ECC or supplement. These data demonstrate that acute muscle-damaging ECC
      increases alpha7beta1 integrin content in human muscle, yet pericyte quantity is
      largely unaltered. Future studies should focus on the capacity for ECC to
      influence pericyte function, specifically paracrine factor release as a mechanism
      toward pericyte contribution to repair and adaptation postexercise. 

PMID- 26205546
TI  - Critical Update of the 2010 Endocrine Society Clinical Practice Guidelines for
      Male Hypogonadism: A Systematic Analysis.
AB  - "Testosterone Therapy in Men With Androgen Deficiency Syndromes: An Endocrine
      Society Clinical Practice Guideline" (Guidelines), published in 2010, serves as
      an important guide for the treatment of hypogonadal men. Using the Guidelines as
      a basis, we searched for the most recent level 1 evidence that continues to
      support the recommendations or provide an impetus to modify all or some of them.
      We performed a systematic analysis with a PubMed query from January 1, 2010,
      through March 2, 2015, using the following key words: testosterone/deficiency,
      testosterone/therapeutic use, cardiovascular, morbidity, mortality, screening,
      sexual function, lower urinary tract symptoms, obstructive sleep apnea, prostate
      cancer, fertility, bone mineral density, osteoporosis, quality of life,
      cognitive, erectile dysfunction, and adverse effects. We identified 17 trials
      representing level 1 evidence that specifically addressed recommendations made in
      the Guidelines. Trials examining outcomes of testosterone replacement therapy in
      men with severe lower urinary tract symptoms and untreated obstructive sleep
      apnea were identified, potentially refuting the current dogma against treatment
      in the setting of these conditions. Hypogonadal men with type 2 diabetes mellitus
      and metabolic syndrome were examined in several trials, demonstrating the
      beneficial effects of therapy on sexual function and insulin sensitivity. Several
      trials served as reinforcing evidence for the beneficial effects of testosterone
      therapy on osteoporosis, muscle strength, and symptoms of frailty. As in the
      Guidelines, inconsistent effects on quality of life, well-being, and erectile
      function were also noted in publications. Despite controversies surrounding
      cardiovascular morbidity and treatment in the setting of prostate cancer, no
      studies examining these issues as primary end points were identified. The low
      number of eligible studies since 2010 is a limitation of this analysis. 

PMID- 26205548
TI  - Recent advances in potential treatment of diabetes and diabetic vascular
      complications by bioactive natural products and new synthetic compounds.

PMID- 26205547
TI  - Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy.
AB  - OBJECTIVE: To examine the risk of venous thromboembolism (VTE) associated with
      exposure to testosterone therapy in middle-aged and older men. PATIENTS AND
      METHODS: We conducted a case-control study of 30,572 men 40 years and older who
      were enrolled in one of the nation's largest commercial insurance programs
      between January 1, 2007, and December 31, 2012. Cases were defined as men who had
      a primary diagnosis of VTE and received an anticoagulant drug in the 60 days
      after their diagnoses. Cases were matched with 3 controls on event/index month,
      age, geographic region, diagnosis of hypogonadism, and diagnosis of any
      underlying prothrombotic condition. Conditional logistic regression analysis was
      used to calculate adjusted odds ratios (aORs) and 95% CIs for the risk of VTE
      associated with previous exposure to testosterone therapy. RESULTS: Exposure to
      testosterone therapy in the 15 days before the event/index date was not
      associated with an increased risk of VTE (aOR, 0.90; 95% CI, 0.73-1.12). None of
      the specific routes of administration examined were associated with an increased
      risk of VTE (topical [aOR, 0.80; 95% CI, 0.61-10.41], transdermal [aOR, 0.91; 95%
      CI, 0.38-2.16], and intramuscular [aOR, 1.15; 95% CI, 0.80-1.64]). These findings
      persisted using exposure windows that extended to 30 and 60 days before the
      event/index date. CONCLUSION: Having filled a prescription for testosterone
      therapy was not associated with an increased risk of VTE in commercially insured
      middle-aged and older men. These findings may provide clinically relevant
      information about the benefit-risk assessment for men with testosterone
      deficiency considering treatment.

PMID- 26205549
TI  - Editorial: New Paradigms in GPCR Drug Discovery.

PMID- 26205550
TI  - Sexually dimorphic effects of maternal dietary protein restriction on fetal
      growth and placental expression of 11beta-HSD2 in the pig.
AB  - Placental 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) inactivates
      glucocorticoids (GCs) to protect fetuses from over-exposure to maternal GCs, yet
      how maternal malnutrition affects placental 11beta-HSD2 expression is unknown. In
      this study, Meishan sows were fed standard-protein (SP) or low-protein (LP, 50%
      of SP) diets and fetuses/newborn piglets were weighed and the corresponding
      placenta and umbilical cord blood were collected on gestational day 70 and the
      day of parturition. Significant growth retardation was observed in female, but
      not male, fetuses (P < 0.05) and the newborns (P < 0.01) of the LP group, which
      was accompanied by sexually dimorphic expression of 11beta-HSD2 in placentas.
      Female fetuses in LP group showed significant decrease in placental 11beta-HSD2
      protein content (P < 0.05) and enzyme activity (P < 0.05), whereas male fetuses
      demonstrated significantly enhanced placental 11beta-HSD2 activity (P < 0.05).
      Serum cortisol levels were significantly higher (P < 0.05) in male piglets
      compared to females, and the effects of maternal protein restriction on thyroid
      hormones (T3 and T4) in the umbilical cord blood were also sex dimorphic. Male
      piglets in LP group had significantly higher T3 (P < 0.01) and lower T4 (P <
      0.01), whereas female piglets showed significantly lower T4 (P < 0.01) with no
      change in T3. As a result, male piglets in LP group exhibited significantly
      higher T3/T4 ratio compared to female counterparts. These results indicate that
      the effects of maternal protein restriction on placental 11beta-HSD2 expression
      are gender-dependent in the pig, and thyroid hormones may be involved in such
      effects.

PMID- 26205551
TI  - JC virus-iLOV fluorescent strains enable the detection of early and late viral
      protein expression.
AB  - JC virus (JCV) is highly prevalent in humans, and may cause progressive
      multifocal leukoencephalopathy (PML), JCV granule cell neuronopathy (JCV GCN),
      JCV encephalopathy (JCVE) and JCV meningitis (JCVM) in immunocompromised
      individuals. There is no treatment for JCV, and a growing number of multiple
      sclerosis patients treated with immunomodulatory medications have developed PML.
      Antiviral agents against JCV are therefore highly desirable but remain elusive,
      due to the difficulty of determining their effect in vitro. A JCV strain carrying
      a fluorescent protein gene would greatly simplify and accelerate the drug
      screening process. To achieve this goal, we selected the 366bp improved Light,
      Oxygen or Voltage-sensing domain (iLOV) of plant phototropin gene and created two
      full-length JCV-iLOV constructs on the prototype JCV Mad1 backbone. The iLOV gene
      was inserted either before the early regulatory T gene (iLOV-T), or after the
      late Agno gene (iLOV-Agno). Both JCV iLOV strains were replication-competent in
      vitro and emitted a fluorescent signal detectable by confocal microscope, but JCV
      iLOV-T exhibited higher cellular and supernatant viral loads compared to JCV iLOV
      Agno. JCV iLOV-T could also produce infectious pseudovirions. These data suggest
      that JCV iLOV constructs may become valuable tools for anti-JCV drug screening. 

PMID- 26205552
TI  - Production of a Sindbis/Eastern Equine Encephalitis chimeric virus inactivated
      cell culture antigen.
AB  - Eastern Equine Encephalitis virus (EEEV) is a medically important pathogen that
      can cause severe encephalitis in humans, with mortality rates ranging from 30 to
      80%. Unfortunately there are no antivirals or licensed vaccines available for
      human use, and laboratory diagnosis is essential to differentiate EEEV infection
      from other pathogens with similar clinical manifestations. The Arboviral Diseases
      Branch (ADB) reference laboratory at the CDC Division of Vector-Borne Diseases
      (DVBD) produces reference antigens used in serological assays such as the EEEV
      immunoglobulin M antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA).
      However, EEEV is classified as a HHS select agent and requires biosafety level
      (BSL) three containment, limiting EEEV antigen production in non-select agent and
      BSL-2 laboratories. A recombinant Sindbis virus (SINV)/EEEV has been constructed
      for use under BSL-2 conditions and is not regulated as a select agent. Cell
      culture production of inactivated EEEV antigen from SINV/EEEV for use in the EEEV
      MAC-ELISA is reported here. Cell culture conditions and inactivation procedures
      were analyzed for SINV/EEEV using a recently developed antigen production
      algorithm, with the MAC-ELISA as the performance indicator. 

PMID- 26205553
TI  - Red blood cell distribution width [RDW] and long-term mortality after community
      acquired pneumonia. A comparison with proadrenomedullin.
AB  - Proadrenomedullin (proADM), a cardiovascular biomarker, has shown high prognostic
      power for community-acquired pneumonia (CAP) outcomes. Red-blood-cell
      distribution width (RDW), linked to cardiovascular disorders, has been associated
      with short-term and medium-term mortality after CAP. Our objective was to assess
      the accuracy of both biomarkers for CAP long-term mortality (>90 days). Adults
      hospitalized with CAP underwent blood proADM, RDW, C-reactive protein (CRP) and
      procalcitonin (PCT) measurements at admission, and were evaluated after 30, 90,
      and 180 days, and 1, 2, and 3 years, until either death or 5 years of follow-up.
      A group of 265 patients were recruited, with an average follow-up 1018 +/- 539
      days. Of these, 217 were followed for 1 year, and 187 for 3 years. Levels of both
      proADM and RDW were higher in those who died in the short term (p = 0.017 and p <
      0.0001, respectively), medium term (p = 0.004 and p < 0.0001, respectively) and
      long term (p < 0.0001 and p < 0.0001, respectively). RDW showed lower accuracy
      (30-day AUC, 0.673) than proADM (AUC, 0.816), PSI (AUC, 0.846), and CURB65 (AUC,
      0.817) scores for short-term and medium-term mortality prediction. However,
      accuracy was similar (3-year AUC, 0.692, 0.698, 0.743, and 0.704, respectively)
      for long-term mortality, and RDW > 14% (RDW > 14) increased the prediction power
      of both PSI (AUC, 0.743 vs 0.779; p < 0.0001) and CURB65 (AUC, 0.704 vs 0.747; p
      < 0.0001) scores, as did proADM. RDW > 14 + PSI and RDW > 14 + CURB65
      associations had a sensitivity for long-term mortality of 80.8%-90% and 74%-90%,
      and a specificity of 56.7%-61.5% and 59.3%-64.2%, respectively. Both proADM and
      RDW > 14 (HR, 4.116) were independent risk factors for long-term mortality and
      were associated with poorer survival. Our findings agree with the suggested
      association between cardiovascular disease and long-term CAP mortality. RDW,
      routinely provided as part of the whole blood count, and especially associated
      with clinical scores, can provide useful information about long-term CAP
      outcomes.

PMID- 26205554
TI  - Impaired quality of life in treatment-seeking obese children of Dutch, Moroccan,
      Turkish and Surinamese descent.
AB  - OBJECTIVE: To determine the health-related quality of life (HRQOL) of overweight
      and obese multi-ethnic children compared with normal-weight children; and to
      investigate differences in HRQOL between self- and parent-proxy reports and
      ethnic groups. DESIGN: Prospective cross-sectional study. SETTING: Out-patient
      clinic where children and their parents filled out a validated HRQOL
      questionnaire (KIDSCREEN-52) and height, weight, waist circumference and fat
      percentage were measured. SUBJECTS: Overweight and obese children, aged 8-18
      years (mean BMI Z-score 3.2 (sd 0.6)), from the obesity out-patient clinic.
      RESULTS: Three hundred and eight self- and 213 parent-proxy reported
      questionnaires were completed. Global HRQOL and the Physical Wellbeing, Moods &
      Emotions and Self-Perception subscales were markedly reduced in our multi-ethnic
      obese cohort, relative to the Dutch reference values. Parent proxies reported
      significantly lower on the global HRQOL and the Physical Wellbeing, Moods &
      Emotions and Bullying subscales. In Caucasian children, multivariate analyses
      showed that BMI was associated with the quality-of-life subscales Moods &
      Emotions, Self-Perception and Bullying. CONCLUSIONS: HRQOL was markedly reduced
      in our multi-ethnic overweight and obese out-patient clinic cohort, with
      significantly lower parent-proxy scores compared with self-reported scores. We
      believe intervention programmes aiming to improve HRQOL should be directed to
      both parents and children, while ethnic-specific programmes to enhance HRQOL seem
      of less importance.

PMID- 26205555
TI  - Ferrocenylmethylation reactions with a phosphinoferrocene betaine.
AB  - A phosphinoferrocene betaine, N-{[1'-(diphenylphosphino)ferrocenyl]methyl}-N,N
      dimethyl-3-sulfo-1-propanaminium, inner salt, Ph2PfcCH2NMe2(CH2)3SO3 (; fc =
      ferrocene-1,1'-diyl), was prepared by alkylation of Ph2PfcCH2NMe2 () with 1,3
      propanesultone, and was studied as a ferrocenylmethylation agent. The treatment
      of with NaOH in hot water-dimethyl sulfoxide produced phosphinoalcohol
      Ph2PfcCH2OH () in a 64% yield, whereas a similar reaction with MeONa in
      dimethylsulfoxide-methanol furnished the corresponding ether, Ph2PfcCH2OMe (), in
      a 47% yield. In subsequent experiments, betaine was employed in the synthesis of
      phosphinoferrocene sulfones, Ph2PfcCH2SO2R, where R = Me (), Ph (), and 4-tolyl
      (). Compounds and some by-products of the ferrocenylmethylation reactions, namely
      alcohol , 1'-(diphenylphosphino)-1-methylferrocene (), and 1-{[diphenyl(2,4
      cyclopentadien-1-ylidene)phosphoranyl]methyl}-1'-(diphenylphosphino)ferrocene ()
      structurally characterised. Reactions of as the representative with ZnX2/NaX (X =
      Br and I) afforded unique coordination polymers [ZnNaX3()(CH3OH)]n featuring
      tetrahedral Zn(ii) and octahedral Na(i) centres bridged by halide ions, solvating
      methanol and the sulfone ligands. The reaction of with ZnBr2/KBr produced an
      analogous product, [ZnKBr3()(CH3OH)]n, while that with ZnBr2/LiBr furnished a
      different, pseudodimeric complex [Zn2Li2Br6()2(CH3OH)4(H2O)].CH3OH, featuring
      tetrahedrally coordinated Zn(ii) and Li(i) centres bridged by . Reactions of with
      ZnBr2/MBr (M = Rb, Cs) and NaCl/ZnCl2 did not yield similar products because of
      an easy precipitation (low solubility) of the respective alkali metal halides. 

PMID- 26205557
TI  - Two mandibular surgical ciliated cysts after Le Fort I osteotomy and genioplasty.
AB  - A surgical ciliated cyst is a locally aggressive lesion that usually develops as
      a delayed complication many years after the initial operation, and we know of few
      reports of its development after orthognathic surgery. We report a case of 2
      mandibular surgical ciliated cysts that developed 28 months after Le Fort I
      osteotomy and genioplasty with bone graft. 

PMID- 26205556
TI  - Changes in monthly unemployment rates may predict changes in the number of
      psychiatric presentations to emergency services in South Australia.
AB  - BACKGROUND: To determine the extent to which variations in monthly Mental Health
      Emergency Department (MHED) presentations in South Australian Public Hospitals
      are associated with the Australian Bureau of Statistics (ABS) monthly
      unemployment rates. METHODS: Times series modelling of relationships between
      monthly MHED presentations to South Australian Public Hospitals derived from the
      Integrated South Australian Activity Collection (ISAAC) data base and the ABS
      monthly unemployment rates in South Australia between January 2004-June 2011.
      RESULTS: Time series modelling using monthly unemployment rates from ABS as a
      predictor variable explains 69% of the variation in monthly MHED presentations
      across public hospitals in South Australia. Thirty-two percent of the variation
      in current month's male MHED presentations can be predicted by using the 2
      months' prior male unemployment rate. Over 63% of the variation in monthly female
      MHED presentations can be predicted by either male or female prior monthly
      unemployment rates. CONCLUSIONS: The findings of this study highlight that even
      with the relatively favourable economic conditions, small shifts in monthly
      unemployment rates can predict variations in monthly MHED presentations,
      particularly for women. Monthly ABS unemployment rates may be a useful metric for
      predicting demand for emergency mental health services.

PMID- 26205558
TI  - Application of clips assisted with foreign body forceps in defect closure after
      endoscopic full-thickness resection.
AB  - BACKGROUND: This study was designed to evaluate the feasibility and efficacy of
      metallic clips assisted with foreign body forceps closing the gastric wall defect
      after endoscopic full-thickness resection (EFR) for gastric submucosal tumors
      (SMTs). METHODS: Eighteen patients with gastric SMTs originated from the
      muscularis propria were treated by EFR between September 2012 and June 2014.
      Twelve patients underwent endoscopic closure of the gastric wall defects after
      EFR with endoloop and metallic clips (endoloop string suture method, ESSM), and
      six patients with clips and foreign body forceps (clips assisted with foreign
      body forceps clip method, CFCM). RESULTS: No significant differences existed
      between the two groups in terms of demographics, clinical characteristics, and
      the size of the gastric wall defects. The average time spent in closing the
      gastric wall defects (14.83 +/- 1.94 min for the CFCM group and 22.42 +/- 5.73
      min for the ESSM group) and hospitalization fees of the CFCM group were
      significantly lower than those of the ESSM group. The average hospitalization
      time of the two groups had no statistical significance. No single case had
      surgical intervention or complications, such as gastric bleeding, perforation,
      peritonitis, or abdominal abscess. CONCLUSION: The CFCM and the ESSM are safe and
      effective techniques for gastric defect closure after EFR for gastric SMTs.
      Because of the "chopsticks effect," the CFCM more suitable for the lesions
      located at the gastric fundus, the greater curvature or anterior wall of the
      gastric body and gastric antrum.

PMID- 26205560
TI  - Single-site laparoscopic approach of Kraske procedure for a presacral local
      recurrence of rectal adenocarcinoma.

PMID- 26205561
TI  - Previous weight loss as a predictor of weight loss outcomes after laparoscopic
      adjustable gastric banding.
AB  - INTRODUCTION: Weight loss after laparoscopic adjustable gastric banding (LAGB)
      can be influenced by a variety of factors. The objective of this study is to
      investigate whether the maximum amount of previous weight loss with diet and
      exercise, prior to evaluation for bariatric surgery, is predictive of
      postoperative weight loss success among primary LAGB patients. METHODS: A
      retrospective cohort study was designed from a prospectively collected database
      at a single institution. Inclusion criteria consisted of age >=18 years, initial
      body mass index (BMI) >=35 kg/m(2), intake information on the maximum weight loss
      at any time prior to referral to our bariatric practice, and at least 2 years of
      postoperative follow-up. Patients with prior bariatric surgery were excluded.
      Outcomes included mean % excess weight loss (EWL), percent that achieved weight
      loss success (%EWL >= 40), and percent with suboptimal weight loss (%EWL < 20) at
      2 years post-LAGB. RESULTS: In the study, 462 primary LAGB patients were
      included. Mean previous weight loss was 29.7 lb (SD 27.6, range 0-175). These
      patients were divided into four previous weight loss groups (0, 1-20, 21-50, >50
      lb) for analysis. In adjusted multivariate analyses, patients with >50 lb of
      maximum previous weight loss had a significantly higher mean %EWL, (p < 0.0001)
      and %BMIL (p < 0.0001), were more likely to reach weight loss success (>=40 %
      EWL, p = 0.047), and were less likely to experience suboptimal weight loss (<20 %
      EWL, p = 0.027) at 2 years postoperatively. CONCLUSION: Previous weight loss
      appears to be a significant predictor of weight loss after LAGB. With multiple
      options for weight loss surgery, this study helps elucidate which patients may be
      more likely to achieve greater weight loss with the LAGB, allowing clinicians to
      appropriately counsel patients preoperatively.

PMID- 26205559
TI  - SAGES TAVAC safety and effectiveness analysis: da Vinci (r) Surgical System
      (Intuitive Surgical, Sunnyvale, CA).
AB  - BACKGROUND: The da Vinci((r)) Surgical System (Intuitive Surgical, Sunnyvale, CA,
      USA) is a computer-assisted (robotic) surgical system designed to enable and
      enhance minimally invasive surgery. The Food and Drug Administration (FDA) has
      cleared computer-assisted surgical systems for use by trained physicians in an
      operating room environment for laparoscopic surgical procedures in general,
      cardiac, colorectal, gynecologic, head and neck, thoracic and urologic surgical
      procedures. There are substantial numbers of peer-reviewed papers regarding the
      da Vinci((r)) Surgical System, and a thoughtful assessment of evidence framed by
      clinical opinion is warranted. METHODS: The SAGES da Vinci((r)) TAVAC sub
      committee performed a literature review of the da Vinci((r)) Surgical System
      regarding gastrointestinal surgery. Conclusions by the sub-committee were vetted
      by the SAGES TAVAC Committee and SAGES Executive Board. Following revisions, the
      document was evaluated by the TAVAC Committee and Executive Board again for final
      approval. RESULTS: Several conclusions were drawn based on expert opinion
      organized by safety, efficacy, and cost for robotic foregut, bariatric,
      hepatobiliary/pancreatic, colorectal surgery, and single-incision
      cholecystectomy. CONCLUSIONS: Gastrointestinal surgery with the da Vinci((r))
      Surgical System is safe and comparable, but not superior to standard laparoscopic
      approaches. Although clinically acceptable, its use may be costly for select
      gastrointestinal procedures. Current data are limited to the da Vinci((r))
      Surgical System; further analyses are needed.

PMID- 26205563
TI  - Enhancing the Value of Statewide Hospital Discharge Data: Improving Clinical
      Content and Race-Ethnicity Data.

PMID- 26205562
TI  - Outcome of laparoscopic gastrectomy with D1 plus lymph node dissection in gastric
      cancer patients postoperatively diagnosed with locally advanced disease or lymph
      node metastasis.
AB  - BACKGROUND: Some laparoscopic gastrectomy (LG) patients are postoperatively
      diagnosed with locally advanced disease or lymph node metastasis. Few reports
      have reviewed the outcomes or validity of LG in such patients. METHODS: We
      retrospectively compared the outcomes of LG for gastric cancer patients
      postoperatively diagnosed with T3 (subserosal invasion) or higher or N1
      (metastasis in 1-2 regional lymph nodes), or higher disease (n = 36), with open
      gastrectomy (OG) for c-stage I gastric cancer patients (n = 62). RESULTS: D1 plus
      lymph node dissection was performed in all patients in the LG group. Blood loss
      was significantly lower in the LG group than in the OG group (P < 0.0010). The
      mean postoperative hospital stay duration was significantly shorter in the LG
      group than in the OG group (P = 0.0016). In the LG group, lymph node metastasis
      occurred in 1 patient, peritoneal dissemination in 2 patients, and liver
      metastasis in 1 patient. The 5-year survival rate did not significantly differ
      between the LG and OG groups (90.00 vs. 94.52 %; P = 0.6517). CONCLUSIONS: Given
      the similarity in long-term outcomes between the LG and OG groups, LG is an
      appropriate indication for gastric cancer patients postoperatively diagnosed with
      locally advanced disease or lymph node metastasis.

PMID- 26205565
TI  - Delayed hypersensitivity reaction after cervical disc replacement: a case report.
AB  - We report a case of allergic reaction after total cervical disc arthroplasty. A
      52-year old woman was operated on for right C6 cervicobrachial neuralgia
      secondary to C5-C6 disc disease with foraminal stenosis. A cobalt-chromium
      molybdenum total disc prosthesis had been implanted two years earlier. The
      patient was referred to our institution for recurrence of axial neck pain
      associated with abdominal patches of erythematous itching rash and swallowing
      disorder. Allergy tests confirmed type-4 allergic reaction to chromium. Symptoms
      decreased after removal of the prosthesis with secondary fusion. Delayed allergic
      reaction is uncommon in spine surgery, but should be considered in case of
      recurrence of initial symptomatology associated with non-spinal signs. 

PMID- 26205567
TI  - Historical Medical Biography: Hagiography and Pathography.

PMID- 26205566
TI  - The posterior condylar offset ratio and femoral anatomy in anterior versus
      posterior referencing total knee arthroplasty.
AB  - BACKGROUND: The preservation of joint anatomy is one of the key issues in total
      knee arthroplasty. The effect of the prosthesis' referencing system, relative to
      femoral anatomy, remains unknown. It was sought to determine if femoral anatomy,
      following total knee arthroplasty is better maintained using either anterior
      referencing or posterior referencing prosthesis. The posterior condylar offset
      ratio (PCOR) was employed for preoperative and postoperative radiographic
      comparison of femoral condyles. It was hypothesized that posterior referencing
      prosthesis would better restore condylar morphology. METHODS: Sixty-six patients
      undergoing a total knee arthroplasty with anterior referenced Zimmer((r))
      NexGen((r)) LPS prosthesis and ninety-one with posterior referenced Tornier((r))
      HLS Noetos((r)) were divided into two groups according to the prosthetic model
      used and retrospectively compared. PCOR was calculated as the quotient of the
      distance between the posterior condylar border and the tangent to the posterior
      cortex of the femoral diaphysis, and the distance between the posterior condylar
      border and the tangent to the anterior cortex of the femoral diaphysis. PCOR was
      determined preoperatively and postoperatively and compared within each group and
      between both groups. RESULTS: An increase in the PCOR (P<0.0001) following
      surgery was observed in both anterior referencing and posterior referencing
      models. No difference was noted when the postoperative PCOR was compared between
      both groups (P=0.61). CONCLUSION: Both anterior and posterior referencing
      prosthesis lead to a similar increase of the PCOR following total knee
      arthroplasty. LEVEL OF EVIDENCE: Level IV.

PMID- 26205568
TI  - The Role and Purpose of Anesthesia Museums in Preserving our Heritage.

PMID- 26205569
TI  - The Backstory to the Earliest-known Extant Motion Picture of Anesthesia.

PMID- 26205570
TI  - An Appraisal of the Life of Charles Thomas Jackson as Attention Deficit
      Hyperactivity Disorder.
AB  - Charles Thomas Jackson claimed to have original ideas that led to the creation of
      guncotton, the electromagnetic telegraph, and the use of ether as an anesthetic.
      There was, though, a gap between when the idea was enunciated and when it became
      reality, with other individuals accomplishing the latter. An examination of
      Charles Jackson's life reveals a pattern of behavior that is compatible with
      attention deficit hyperactivity disorder with an associated diagnosis of
      oppositional defiant disorder. These diagnoses are explored in the context of
      Jackson's life to explain why he did not carry his initial thoughts to fruition. 

PMID- 26205571
TI  - The Japanese Museum of Anesthesiology in Kobe, Japan.
AB  - In 2009, the Japanese Society of Anesthesiologists (JSA) founded the Archives of
      JSA, which changed into the Japanese Museum of Anesthesiology in 2011. The museum
      consists of three sections: (1) archives (the collection of historical documents
      of the JSA), (2) museum (the collection of anesthetic equipment and its related
      things), and (3) library (the collection of books, journals, leaflets, and
      related materials). By January 2013, the collections included 2537 Japanese and
      1569 foreign language books. JMA collections include 25% of the Japanese
      anesthesia books published between 1796-2008, making it Japan's largest
      collection, with the exception of the National Diet Library of Japan. Most of the
      Japanese books published from 1796 to 2008 are listed and can be searched through
      the home page. 

PMID- 26205572
TI  - Lower Body Negative Pressure: Historical Perspective, Research Findings, and
      Clinical Applications.
AB  - Lower body negative pressure (LBNP) is a technique that redistributes blood from
      the upper body to the dependent regions of the pelvis and legs, thus reducing
      central venous pressure and venous return. The subject is placed in a cylindrical
      air-tight metal tank, which is sealed at the level of the iliac crests, and
      subatmospheric pressure is produced using a vacuum pump. This article reviews the
      historical background, physiological effects, research findings, and clinical
      applications of LBNP. LBNP is found in both the basic science and clinical
      literature, encompassing its diverse investigational and clinical applications.
      The first references to LBNP were in 1952 describing its effectiveness in
      inducing hypotensive anesthesia. Major interest in LBNP began in the mid 1960s
      when it was used to characterize the cardiovascular responses to hemorrhage and
      orthostatic stress, especially that associated with the weightlessness of space
      flight; these studies have continued to the present day. Advantages of LBNP for
      such experimental studies include the following: (1) The degree of central
      hypovolemia is easily controlled and has a rapid onset and reversal. (2) The
      technique is repeatable, reproducible, and noninvasive. (3) No exogenous
      pharmacologic agent is required to produce venous pooling. (4) The findings are
      independent of gravity. In recent years, a few institutions have applied LBNP
      clinically to diagnose abnormalities in cardiovascular autonomic function and,
      when combined with echocardiography, to uncover changes in cardiac performance
      through analysis of Starling curves. 

PMID- 26205573
TI  - The Earliest-Known Extant Motion Picture of Anesthesia in the World was Filmed in
      Buenos Aires.

PMID- 26205574
TI  - Exposure of Surgeons to Magnetic Fields during Laparoscopic and Robotic
      Gynecologic Surgeries.
AB  - STUDY OBJECTIVE: To measure and compare levels of extremely-low-frequency
      magnetic field (ELF-MF) exposure to surgeons during laparoscopic and robotic
      gynecologic surgeries. DESIGN: Prospective case-control study. DESIGN
      CLASSIFICATION: Canadian Task Force I. SETTING: Gynecologic surgeries at the
      Yonsei University Health System in Seoul, Korea from July to October in 2014.
      PATIENTS: Ten laparoscopic gynecologic surgeries and 10 robotic gynecologic
      surgeries. INTERVENTION: The intensity of ELF-MF exposure to surgeons was
      measured every 4 seconds during 10 laparoscopic gynecologic surgeries and 10
      robotic gynecologic surgeries using portable ELF-MF measuring devices with
      logging capability. MEASUREMENT AND MAIN RESULTS: The mean ELF-MF exposures were
      .1 +/- .1 mG for laparoscopic gynecologic surgeries and .3 +/- .1 mG for robotic
      gynecologic surgeries. ELF-MF exposure levels to surgeons during robotic
      gynecologic surgery were significantly higher than those during laparoscopic
      gynecologic surgery (p < .001) after adjustment for duration of measurement.
      CONCLUSION: The present study demonstrated low levels of ELF-MF exposure to
      surgeons during robotic gynecologic surgery and conventional laparoscopic
      surgery, hoping to alleviate concerns regarding the hazards of MF exposure posed
      to surgeons and hospital staff.

PMID- 26205575
TI  - Hysteroscopic Resection in Fertility-Sparing Surgery for Atypical Hyperplasia and
      Endometrial Cancer: How Important Are Intrauterine Adhesions?

PMID- 26205576
TI  - Reply to "Hysteroscopic Resection in Fertility-Sparing Surgery for Atypical
      Hyperplasia and Endometrial Cancer: How Important are Intrauterine Adhesions?".

PMID- 26205577
TI  - A Case of Extragonadal Teratoma in the Pouch of Douglas and Literature Review.
AB  - Mature cystic teratoma is a germ cell tumor of the ovaries and is often observed
      in clinical practice. However, extragonadal teratomas are rare tumors and have
      been reported outside the ovaries, (e.g., in the greater omentum). The mechanism
      underlying the development of extragonadal teratomas remains unknown. We
      encountered a case of extragonadal teratoma in the pouch of Douglas that appeared
      to be a parasitic dermoid cyst. From our experience and the literature review, we
      discuss the potential mechanism leading to the development of extragonadal
      teratomas. A 41-year-old nonpregnant woman was referred to our department due to
      myoma and anemia. A 4-cm asymptomatic mass in the pouch of Douglas was observed,
      and the patient was diagnosed with ovarian mature cystic teratoma. She underwent
      laparoscopic surgery, and intraoperative findings revealed that the fallopian
      tube was injured and torn, and a residual small ovary was observed in the left
      side of the ovary. A tumor measuring approximately 4 cm observed in the pouch of
      Douglas was extracted without rupturing. The tumor was diagnosed as a parasitic
      dermoid cyst by macroscopic and histopathological findings. Auto-amputation could
      be the underlying mechanism that leads to an isolated parasitic dermoid cyst in
      the pouch of Douglas.

PMID- 26205578
TI  - Vaginal Uterine Morcellation Within a Specimen Containment System: A Study of Bag
      Integrity.
AB  - STUDY OBJECTIVE: To evaluate the integrity of the endoscopic bag after
      transvaginal in-bag morcellation of uteri that need to be removed by vaginal
      morcellation during total laparoscopic hysterectomy (TLH). DESIGN: Prospective
      pilot study (Canadian Task Force classification II-2). SETTING: University
      hospital. PATIENTS: Twelve patients with uteri that needed to be removed and who
      required vaginal morcellation underwent TLH from September 2014 to February 2015,
      without suspected or confirmed malignancy. INTERVENTIONS: After transvaginal in
      bag morcellation of uteri at the end of TLH, careful visual inspection of the
      endoscopic pouch, using diluted methylene blue, was carried out, highlighting any
      minimal bag damage. MEASUREMENTS AND MAIN RESULTS: No gross rupture was
      encountered after morcellation; however, 4 minimal ruptures were recognized (33%)
      after filling up the bag with diluted methylene blue. CONCLUSIONS: Minimal
      lesions of the bag may occur after transvaginal morcellation of uteri that need
      to be removed by vaginal morcellation; this may potentially affect the spread of
      cancer cells into the abdominal cavity.

PMID- 26205580
TI  - T cells: A killer cytokine.

PMID- 26205579
TI  - Unique microRNAs appear at different times during the course of a delayed-type
      hypersensitivity reaction in human skin.
AB  - Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH)
      reactions. MicroRNAs (miRNAs) are short non-coding RNAs that negatively regulate
      gene expression and have been implicated in various inflammatory skin diseases,
      but their role in DTH reactions is not well understood. We generated global miRNA
      expression profiles (using next-generation sequencing) of DPCP reactions in skin
      of seven healthy volunteers at 3, 14 and 120 days after challenge. Compared to
      placebo-treated sites, DPCP-challenged skin at 3 days (peak inflammation) had 127
      miRNAs significantly deregulated. At 14 days (during resolution of inflammation),
      43 miRNAs were deregulated and, at 120 days (when inflammation had completely
      resolved), six miRNAs were upregulated. While some miRNAs have been observed in
      psoriasis or atopic dermatitis, most of the deregulated miRNAs have not yet been
      studied in the context of skin biology or immunology. Across the three time
      points studied, many but not all miRNAs were uniquely expressed. As various
      miRNAs may influence T cell activation, this may indicate that the miRNAs
      exclusively expressed at different time points function to promote or resolve
      skin inflammation, and therefore, may inform on the paradoxical ability of DPCP
      to treat both autoimmune conditions (alopecia areata) and conditions of
      ineffective immunity (melanoma).

PMID- 26205581
TI  - Mucosal immunology: Microbiota-induced T cells block allergic inflammation.

PMID- 26205582
TI  - Dcs tailor T cells to the tissue.

PMID- 26205585
TI  - Bioanalytical method for the simultaneous determination of D- and L-serine in
      human plasma by LC/MS/MS.
AB  - D-Serine is an endogenous modulator of N-methyl-D-aspartate (NMDA) receptors.
      Plasma concentrations of D-serine and the ratio of D-serine to total serine may
      be used as clinically-translatable biomarkers in NMDA receptor-related disease.
      We developed a highly sensitive and specific method using high performance liquid
      chromatography tandem mass spectrometry (LC/MS/MS) for the simultaneous
      determination of the D- and L-isomers of serine in human plasma. Since D- and L
      serine are endogenous components, phosphate buffered saline was used as the
      surrogate matrix. D- and L-serine in human plasma and PBS were treated by
      cationic exchange solid phase extraction. D-Serine (m/z 106.1 > 60.0), L-serine
      (m/z 106.1 > 60.1) and DL-serine-d3 (m/z 109.1 > 63.0) were detected using a
      multiple reaction monitoring. The enantiomer separation of D- and L-serine was
      successfully achieved without any derivatization step using tandemly-arranged and
      ice-cold CROWNPAK CR-I(+) columns with an isocratic mobile phase comprised of
      0.3% trifluoroacetic acid in 10% acetonitrile. The standard curves were linear
      throughout the calibration range with 0.01-10 MUg/mL (D-serine) and 0.1-100
      MUg/mL (L-serine), respectively. Intra-day and inter-day precision and accuracy
      of the quality control samples were within relative standard deviations of less
      than 15%. The endogenous concentrations of D- and L-serine in human plasma were
      0.124-0.199 and 7.97-13.1 MUg/mL, respectively.

PMID- 26205584
TI  - A time-resolved Forster resonance energy transfer assay to measure activity of
      the deamidase of the prokaryotic ubiquitin-like protein.
AB  - The modification of proteins in Mycobacterium tuberculosis (Mtb) by the
      prokaryotic ubiquitin-like protein (Pup) targets them for degradation by
      mycobacterial proteasomes. Although functionally similar to eukaryotic
      deubiquitylating enzymes, the deamidase of Pup, called Dop, has no known
      mammalian homologs. Because Dop is necessary for persistent infection by Mtb, its
      selective inhibition holds potential for tuberculosis therapy. To facilitate high
      throughput screens for Dop inhibitors, we developed a time-resolved Forster
      resonance energy transfer (TR-FRET)-based assay for Dop function. The TR-FRET
      assay was successfully applied to determine the Michaelis constant for adenosine
      triphosphate (ATP) binding and to test the cofactor tolerance of Dop. 

PMID- 26205583
TI  - Molecular and cellular insights into T cell exhaustion.
AB  - In chronic infections and cancer, T cells are exposed to persistent antigen
      and/or inflammatory signals. This scenario is often associated with the
      deterioration of T cell function: a state called 'exhaustion'. Exhausted T cells
      lose robust effector functions, express multiple inhibitory receptors and are
      defined by an altered transcriptional programme. T cell exhaustion is often
      associated with inefficient control of persisting infections and tumours, but
      revitalization of exhausted T cells can reinvigorate immunity. Here, we review
      recent advances that provide a clearer molecular understanding of T cell
      exhaustion and reveal new therapeutic targets for persisting infections and
      cancer. 

PMID- 26205586
TI  - Design and performance of a sericin-alginate interpenetrating network hydrogel
      for cell and drug delivery.
AB  - Although alginate hydrogels have been extensively studied for tissue engineering
      applications, their utilization is limited by poor mechanical strength, rapid
      drug release, and a lack of cell adhesive ability. Aiming to improve these
      properties, we employ the interpenetrating hydrogel design rationale. Using
      alginate and sericin (a natural protein with many unique properties and a major
      component of silkworm silk), we develop an interpenetrating polymer network (IPN)
      hydrogel comprising interwoven sericin and alginate double networks. By adjusting
      the sericin-to-alginate ratios, IPNs' mechanical strength can be adjusted to meet
      stiffness requirements for various tissue repairs. The IPNs with high sericin
      content show increased stability during degradation, avoiding pure alginate's
      early collapse. These IPNs have high swelling ratios, benefiting various
      applications such as drug delivery. The IPNs sustain controlled drug release with
      the adjustable rates. Furthermore, these IPNs are adhesive to cells, supporting
      cell proliferation, long-term survival and migration. Notably, the IPNs inherit
      sericin's photoluminescent property, enabling bioimaging in vivo. Together, our
      study indicates that the sericin-alginate IPN hydrogels may serve as a versatile
      platform for delivering cells and drugs, and suggests that sericin may be a
      building block broadly applicable for generating IPN networks with other
      biomaterials for diverse tissue engineering applications. 

PMID- 26205587
TI  - Synthesis of Aryl Sulfides: Metal-Free C-H Sulfenylation of Electron-Rich Arenes.
AB  - A simple, efficient, and practical metal-free C-H sulfenylation of substituted
      electron-rich arenes has been developed. This method is highly regioselective,
      and the corresponding aryl sulfides were obtained in moderate to excellent yields
      from stable and readily accessible N-(alkylthio)- and N-(arylthio)succinimides at
      room temperature in the presence of TFA. 

PMID- 26205588
TI  - Seroprevalence report on tick-borne encephalitis virus and Crimean-Congo
      hemorrhagic fever virus among Malaysian's farm workers.
AB  - BACKGROUND: Tick-borne encephalitis virus (TBEV) and Crimean-Congo haemorrhagic
      fever virus (CCHFV) are important tick-borne viruses. Despite their wide
      geographical distribution and ease of acquisition, the prevalence of both viruses
      in Malaysia is still unknown. This study was conducted to determine the
      seroprevalence for TBEV and CCHFV among Malaysian farm workers as a high-risk
      group within the population. METHODS: We gave questionnaires to 209 farm workers
      and invited them to participate in the study. Eighty-five agreed to do so. We
      then collected and tested sera for the presence of anti-TBEV IgG (immunoglobulin
      G) and anti-CCHFV IgG using a commercial enzyme-linked immunosorbent assay
      (ELISA) kit. We also tested seroreactive samples against three other related
      flaviviruses: dengue virus (DENV), West Nile virus (WNV) and Japanese
      encephalitis virus (JEV) using the ELISA method. RESULTS: The preliminary results
      showed the presence of anti-TBEV IgG in 31 (36.5%) of 85 sera. However, when
      testing all the anti-TBEV IgG positive sera against the other three antigenically
      related flaviviruses to exclude possible cross reactivity, only five (4.2%) sera
      did not show any cross reactivity. Interestingly, most (70.97%) seropositives
      subjects mentioned tick-bite experience. However, there was no seroreactive
      sample for CCHFV. CONCLUSIONS: These viruses migrate to neighbouring countries so
      they should be considered threats for the future, despite the low seroprevalence
      for TBEV and no serological evidence for CCHFV in this study. Therefore, further
      investigation involving a large number of human, animal and tick samples that
      might reveal the viruses' true prevalence is highly recommended.

PMID- 26205589
TI  - Plaque Characterization by Coronary Computed Tomography Angiography and the
      Likelihood of Acute Coronary Events in Mid-Term Follow-Up.
AB  - BACKGROUND: Coronary computed tomography angiography (CTA)-verified positive
      remodeling and low attenuation plaques are considered morphological
      characteristics of high-risk plaque (HRP) and predict short-term risk of acute
      coronary syndrome (ACS). OBJECTIVES: This study evaluated whether plaque
      characteristics by CTA predict mid-term likelihood of ACS. METHODS: The presence
      of HRP and significant stenosis (SS) of >=70% were evaluated in 3,158 patients
      undergoing CTA. Serial CTA was performed in 449 patients, and plaque progression
      (PP) was evaluated. Outcomes (fatal and nonfatal ACS) were recorded during follow
      up (mean 3.9 +/- 2.4 years). RESULTS: ACS occurred in 88 (2.8%) patients: 48
      (16.3%) of 294 HRP(+) and 40 (1.4%) of 2,864 HRP(-) patients. ACS was also
      significantly more frequent in SS(+) (36 of 659; 5.5%) than SS(-) patients (52 of
      2,499; 2.1%). HRP(+)/SS(+) (19%) and HRP(+)/SS(-) (15%) had higher rates of ACS
      compared with no-plaque patients (0.6%). Although ACS incidence was relatively
      low in HRP(-) patients, the cumulative number of patients with ACS developing
      from HRP(-) lesions (n = 43) was similar to ACS patients with HRP(+) lesions (n =
      45). In patients with serial CTA, PP also was an independent predictor of ACS,
      with HRP (27%; p < 0.0001) and without HRP (10%) compared with HRP(-)/PP(-)
      patients (0.3%). CONCLUSIONS: CTA-verified HRP was an independent predictor of
      ACS. However, the cumulative number of ACS patients with HRP(-) was similar to
      patients with HRP(+). Additionally, plaque progression detected by serial CTA was
      an independent predictor of ACS.

PMID- 26205590
TI  - Progress in the Noninvasive Detection of High-Risk Coronary Plaques.

PMID- 26205591
TI  - Presentation, Diagnosis, and Outcomes of Acute Aortic Dissection: 17-Year Trends
      From the International Registry of Acute Aortic Dissection.
AB  - BACKGROUND: Diagnosis, treatment, and outcomes of acute aortic dissection (AAS)
      are changing. OBJECTIVES: This study examined 17-year trends in the presentation,
      diagnosis, and hospital outcomes of AAD from the International Registry of Acute
      Aortic Dissection (IRAD). METHODS: Data from 4,428 patients enrolled at 28 IRAD
      centers between December 26, 1995, and February 6, 2013, were analyzed. Patients
      were divided according to enrollment date into 6 equal groups and by AAD type: A
      (n = 2,952) or B (n = 1,476). RESULTS: There was no change in the presenting
      complaints of severe or worst-ever pain for type A and type B AAD (93% and 94%,
      respectively), nor in the incidence of chest pain (83% and 71%, respectively).
      Use of computed tomography (CT) for diagnosis of type A increased from 46% to 73%
      (p < 0.001). Surgical management for type A increased from 79% to 90% (p <
      0.001). Endovascular management of type B increased from 7% to 31% (p < 0.001).
      Type A in-hospital mortality decreased significantly (31% to 22%; p < 0.001), as
      surgical mortality (25% to 18%; p = 0.003). There was no significant trend in in
      hospital mortality in type B (from 12% to 14%). CONCLUSIONS: Presenting symptoms
      and physical findings of AAD have not changed significantly. Use of chest CT
      increased for type A. More patients in both groups were managed with
      interventional procedures: surgery in type A and endovascular therapy in type B.
      A significant decrease in overall in-hospital mortality was seen for type A but
      not for type B.

PMID- 26205592
TI  - Gratitude to the International Registry of Acute Aortic Dissection From the
      Aortic Community.

PMID- 26205593
TI  - Outcomes of Percutaneous Coronary Intervention Performed at Offsite Versus Onsite
      Surgical Centers in the United Kingdom.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly being
      performed at centers with offsite surgical support. Strong guideline endorsement
      of this practice has been lacking, in part because outcome data are limited to
      modest-size populations with short-term follow-up. OBJECTIVES: The aim of this
      study was to compare the outcomes of PCI performed at centers with and without
      surgical support in the United Kingdom between 2006 and 2012. METHODS: A
      retrospective analysis was performed of centrally tracked outcomes from index PCI
      procedures entered in the British Cardiovascular Intervention Society database
      between 2006 and 2012, stratified according to whether procedures were performed
      at centers with onsite or offsite surgical support. The primary endpoint was 30
      day all-cause mortality, with secondary endpoints of mortality at 1 and 5 years.
      RESULTS: Outcomes at a median of 3.4 years follow-up were available for 384,013
      patients, of whom 31% (n = 119,096) were treated at offsite surgical centers. In
      an unadjusted analysis, crude mortality rates were lower in patients treated at
      centers with offsite versus onsite surgical coverage (2.0% vs. 2.2%; p < 0.001).
      On multivariate adjustment, there were no between-group differences in survival
      between the naive and imputed populations at 30 days (naive population hazard
      ratio [HR]: 0.87; 95% confidence interval [CI]: 0.71 to 1.06; p = 0.16; imputed
      population HR: 0.99; 95% CI: 0.89 to 1.09; p = 0.82), 1 year (naive population
      HR: 0.92; 95% CI: 0.79 to 1.07; p = 0.26; imputed population HR: 0.99; 95% CI:
      0.92 to 1.06; p = 0.78), or 5 years (naive population HR: 0.92; 95% CI: 0.84 to
      1.01; p = 0.10; imputed population HR: 0.97; 95% CI: 0.92 to 1.03; p = 0.29).
      Results were consistent irrespective of procedural indication. No differences in
      mortality were seen in sensitivity analyses performed using a propensity-matched
      population of 74,001 patients. CONCLUSIONS: PCI performed at centers without
      onsite surgical backup is not associated with any mortality hazard.

PMID- 26205594
TI  - Percutaneous Coronary Intervention Without Onsite Cardiac Surgery: Ready for Take
      Off?

PMID- 26205596
TI  - Exercise Echocardiography in Connective Tissue Disease.

PMID- 26205595
TI  - Prediction of Future Overt Pulmonary Hypertension by 6-Min Walk Stress
      Echocardiography in Patients With Connective Tissue Disease.
AB  - BACKGROUND: Early detection of pulmonary hypertension (PH) in connective tissue
      disease (CTD) is crucial to ensuring that patients receive timely treatment for
      this progressive disease. Exercise stress tests have been used to screen patients
      in an attempt to identify early-stage PH. Recent studies have described abnormal
      mean pulmonary artery pressure (mPAP)-cardiac output (Q) responses as having the
      potential to assess the disease state. OBJECTIVES: This study hypothesized that
      pulmonary circulation pressure-flow relationships obtained by 6-min walk (6MW)
      stress echocardiography would better delineate differential progression of PH and
      predict development of PH during follow-up. METHODS: We prospectively performed
      6MW stress echocardiographic studies in 78 CTD patients (age 58 +/- 12 years; 9%
      male) at baseline and follow-up. All patients underwent yearly echocardiographic
      follow-up studies for up to 5 years. RESULTS: During a median period of 32 months
      (range: 15 to 62 months), 16 patients reached the clinical endpoint of
      development of PH and none died during follow-up. PH was confirmed by right heart
      catheterization in all 16 patients (mPAP >=25 mm Hg and pulmonary capillary wedge
      pressure <=15 mm Hg). In a Cox proportional-hazards survival model, 6MW distance
      (hazard ratio [HR]: 0.99; p = 0.010), early diastolic tricuspid annulus motion
      velocity (HR: 0.79; p = 0.025), and DeltamPAP/DeltaQ by 6MW stress (HR: 1.10; p =
      0.005) were associated with development of PH. In sequential Cox models, a model
      on the basis of 6MW distance (chi-square, 6.6) was improved by DeltamPAP/DeltaQ
      (chi-square: 14.4; p = 0.019). Using a receiver-operating characteristic curve,
      we found that the best cutoff value of DeltamPAP/DeltaQ for predicting
      development of pulmonary hypertension was >3.3 mm Hg/l/min. CONCLUSIONS: The 6MW
      stress echocardiography noninvasively provides an incremental prognostic value of
      PH development in CTD. This is a single-center prospective cohort study. Larger
      multicenter studies are warranted to confirm this result.

PMID- 26205598
TI  - The Power Is in the Numbers: Using Collaboration and a Data Registry to Answer
      Our Burning Questions Regarding Fetal Cardiac Intervention.

PMID- 26205597
TI  - International Fetal Cardiac Intervention Registry: A Worldwide Collaborative
      Description and Preliminary Outcomes.
AB  - BACKGROUND: Invasive fetal cardiac intervention (FCI) has been reported in single
      institution series, promoting technical and physiologic success. OBJECTIVES: This
      study describes the creation of an international registry of cases presenting for
      FCI, intended to compile technical and outcome data from a multicenter cohort.
      METHODS: For this initial analysis, the entire database of the International
      Fetal Cardiac Intervention Registry (IFCIR) was queried for details of diagnoses,
      procedures, and outcomes. Maternal-fetal dyads from January 2001 through June
      2014 were included. RESULTS: Eighteen institutions submitted data by data
      harvest. Of 370 cases entered, 245 underwent FCI: 100 aortic valvuloplasties from
      a previous single-center report (excluded from additional reporting here), an
      additional 86 aortic and 16 pulmonary valvuloplasties, 37 atrial septal cases,
      and 6 unclassified cases. FCI did not appear to affect overall survival to
      hospital discharge. Among live-born infants with a fetal diagnosis of aortic
      stenosis/evolving hypoplastic left heart syndrome, more than twice as many were
      discharged with biventricular circulation after successful FCI versus those
      meeting institutional criteria but without any or successful FCI (42.8% vs.
      19.4%, respectively). When fetal deaths were counted as treatment failures, the
      percentages were similar: biventricular circulation at discharge was 31.3% versus
      18.5% for those discharged with univentricular palliation. Survival to discharge
      for live-born fetuses with atrial restriction was similar to that of those
      undergoing technically successful versus unsuccessful FCI (63.6% vs. 46.7%,
      respectively), although criteria for diagnosis were nonuniform. CONCLUSIONS: We
      describe the contents of the IFCIR and present post-natal data to suggest
      potential benefit to fetal therapy among pregnancies considered for possible
      intervention and support proposals for additional work.

PMID- 26205600
TI  - Addressing the Maintenance of Certification Crisis Calls for Working Together.

PMID- 26205599
TI  - The Early Repolarization Pattern: A Consensus Paper.
AB  - The term early repolarization has been in use for more than 50 years. This
      electrocardiographic pattern was considered benign until 2008, when it was linked
      to sudden cardiac arrest due to idiopathic ventricular fibrillation. Much
      confusion over the definition of early repolarization followed. Thus, the
      objective of this paper was to prepare an agreed definition to facilitate future
      research in this area. The different definitions of the early repolarization
      pattern were reviewed to delineate the electrocardiographic measures to be used
      when defining this pattern. An agreed definition has been established, which
      requires the peak of an end-QRS notch and/or the onset of an end-QRS slur as a
      measure, denoted Jp, to be determined when an interpretation of early
      repolarization is being considered. One condition for early repolarization to be
      present is Jp >=0.1 mV, while ST-segment elevation is not a required criterion. 

PMID- 26205601
TI  - The Evolving Future of Cardiovascular Practice: Technology + Clinicians: A Means
      to a Better End.

PMID- 26205602
TI  - The Changing Face of Interventional Cardiology Training: A Fellow's Perspective.

PMID- 26205603
TI  - Direct Catheter-Based Thrombectomy for Acute Ischemic Stroke: Outcomes of
      Consecutive Patients Treated in Interventional Cardiology Centers in Close
      Cooperation With Neurologists.

PMID- 26205604
TI  - Net Clinical Benefit for Oral Anticoagulation, Aspirin, or No Therapy in
      Nonvalvular Atrial Fibrillation Patients With 1 Additional Risk Factor of the
      CHA2DS2-VASc Score (Beyond Sex).

PMID- 26205605
TI  - Reply: Stent Type and Risk of Late Cerebral Events After Carotid Artery Stenting.

PMID- 26205606
TI  - Stent Type and Risk of Late Cerebral Events After Carotid Artery Stenting.

PMID- 26205607
TI  - Don't Throw the Baby Out With the Bath Water.

PMID- 26205608
TI  - Reply: Primum Non Nocere: First Do No Harm.

PMID- 26205610
TI  - Can you treat the cheat in sports?
AB  - This editorial examines the issue of "cheating" (broadly defined) in sports from
      youth through professional sports. We describe possible underlying causes
      focusing on the development of a "personality disorder" and
      psychiatric/psychodynamic needs (e.g. a pathological need to be the best). We
      detail treatment and management from a medical-psychiatric perspective as well as
      implications for coaches, teams, leagues and professional organizations (e.g.
      soccer, bicycling, etc). Cheating behavior exists in other fields, for example,
      politics, law among others and some of the management principles mentioned here
      may apply there. 

PMID- 26205609
TI  - Disclosure of research results: a randomized study on GENEPSO-PS cohort
      participants.
AB  - BACKGROUND: There exist no recommendations as to how aggregate research results
      should best be disclosed to long-term cohort participants. OBJECTIVE: To study
      the impact of cohort results disclosure documents of various kinds on
      participants' satisfaction. DESIGN: Randomized study with a 2x2 factorial design.
      SETTING AND PARTICIPANTS: The GENEPSO-PS cohort is used to study the psychosocial
      characteristics and preventive behaviour of both BRCA1/2 carriers and non
      carriers; 235 participants wishing to receive 'information about the survey
      results' answered a self-administered questionnaire. INTERVENTIONS: The impact of
      providing the following items in addition to a leaflet about aggregate
      psychosocial research results was investigated (i) an up-to-date medical
      information sheet about BRCA1/2 genetic topics, (ii) a photograph with the names
      of the researchers. MAIN OUTCOME MEASURES: Satisfaction profiles drawn up using
      cluster analysis methods. RESULTS: Providing additional medical and/or research
      team information had no significant effect on satisfaction. The patients
      attributed to the 'poorly satisfied' group (n = 60, 25.5%) differed significantly
      from those in the 'highly satisfied' group (n = 51, 21.7%): they were younger
      [odds ratio (OR) = 0.96, 95% confidence interval (0.92-0.99), P = 0.028], less
      often had a daughter [OR = 4.87 (1.80-13.20), P = 0.002], had reached a higher
      educational level [OR = 2.94 (1.24-6.95), P = 0.014] and more frequently carried
      a BRCA1/2 mutation [OR = 2.73 (1.20-6.23), P = 0.017]. CONCLUSIONS: This original
      approach to disclosing research results to cohort participants was welcomed by
      most of the participants, but less by the more educated and by BRCA1/2 carriers.
      Although an easily understandable document is necessary, it might also be worth
      providing some participants with more in-depth information.

PMID- 26205611
TI  - High-power THz to IR emission by femtosecond laser irradiation of random 2D
      metallic nanostructures.
AB  - Terahertz (THz) spectroscopic sensing and imaging has identified its potentials
      in a number of areas such as standoff security screening at portals, explosive
      detection at battle fields, bio-medical research, and so on. With these needs,
      the development of an intense and broadband THz source has been a focus of THz
      research. In this work, we report an intense (~10 mW) and ultra-broadband (~150
      THz) THz to infrared (IR) source with a Gaussian wavefront, emitted from nano
      pore-structured metallic thin films with femtosecond laser pulse excitation. The
      underlying mechanism has been proposed as thermal radiation. In addition, an
      intense coherent THz signal was generated through the optical rectification
      process simultaneously with the strong thermal signal. This unique feature opens
      up new avenues in biomedical research. 

PMID- 26205612
TI  - Louping ill virus in the UK: a review of the hosts, transmission and ecological
      consequences of control.
AB  - Louping ill virus (LIV) is a tick-borne flavivirus that is part of the tick-borne
      encephalitis complex of viruses (TBEV) and has economic and welfare importance by
      causing illness and death in livestock, especially sheep, Ovies aries, and red
      grouse, Lagopus lagopus scoticus, an economically valuable gamebird. Unlike
      Western TBEV which is found primarily in woodlands and is reservoired by small
      rodents, LIV is not generally transmitted by small rodents but instead by sheep,
      red grouse and mountain hares and, therefore, is associated with upland heather
      moorland and rough grazing land. Red grouse are a particularly interesting
      transmission host because they may acquire most of their LIV infections through
      eating ticks rather than being bitten by ticks. Furthermore, the main incentive
      for the application of LIV control methods is not to protect sheep, but to
      protect red grouse, which is an economically important gamebird. The widespread
      intensive culling of mountain hares which has been adopted in several areas of
      Scotland to try to control ticks and LIV has become an important issue in
      Scotland in recent years. This review outlines the reservoir hosts and
      transmission cycles of LIV in the UK, then describes the various control methods
      that have been tried or modelled, with far-reaching implications for conservation
      and public opinion. 

PMID- 26205613
TI  - The incremental benefits of implementing effective cervical cancer screening.

PMID- 26205614
TI  - TLR4 stimulation by LPS enhances angiogenesis in a co-culture system consisting
      of primary human osteoblasts and outgrowth endothelial cells.
AB  - The development of new approaches leading to fast and successful vascularization
      of tissue-engineered constructs is one of the most intensively studied subjects
      in tissue engineering and regenerative medicine. Recently, TLR4 activation and
      LPS stimulation of endothelial cells have been reported to promote angiogenesis
      in a variety of settings. In this study, we demonstrate that TLR4 activation by
      Ultrapure LPS Escherichia coli 0111:B4 (LPS-EB) significantly enhances
      microvessel formation in a co-culture system consisting of outgrowth endothelial
      cells (OECs) and primary human osteoblasts (pOBs). The precise modes of TLR4
      action on the process of angiogenesis have also been investigated in this study.
      Using quantitative fluorescence microscopy in monocultures of OECs and pOBs, it
      was found that TLR4 activation through LPS-EB upregulates the expression level of
      TLR4/MYD88 and enhances both angiogenesis and osteogenesis. Furthermore, ELISA
      and qRT-PCR have shown that the level of two adhesion molecules (ICAM-1 and E
      selectin), two cytokines (IL-6 and IL-8) and two growth factors (VEGF and PDGF
      BB) related to angiogenesis increase significantly after LPS-EB treatment. This
      increased understanding of the role of TLR4 in angiogenesis could be of value in
      various settings related to tissue repair and tissue engineering. Moreover, since
      LPS and TLR4 agonists improve angiogenesis and osteogenesis, TLR4 agonists
      (endogenous or synthetic) could be used for angiogenesis intervention in vivo and
      therefore could be tested for their potential clinical applications in promoting
      angiogenesis in bone tissue engineering. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 26205615
TI  - Saliva proteome profiling reveals potential salivary biomarkers for detection of
      oral cavity squamous cell carcinoma.
AB  - Oral cavity squamous cell carcinoma (OSCC), which is frequently associated with
      poor prognosis and mortality, is a leading cause of cancer-related death
      worldwide. Discovery of body fluid accessible biomarkers is needed to improve
      OSCC screening. To this end, we profiled proteomes of saliva from the healthy
      volunteers, the individuals with oral potentially malignant disorders (OPMD), and
      the OSCC patients by means of SDS-PAGE coupled with LC-MS/MS. In the control, the
      OPMD, and the OSCC groups, 958, 845, and 1030 salivary proteins were detected,
      respectively. With spectral counting-based label-free quantification, 22
      overexpressed salivary proteins were identified in the OSCC group compared with
      the healthy controls and the OPMD individuals. Among them, resistin (RETN) was
      subjected to further validation with an independent cohort using ELISA. The data
      confirmed that the salivary RETN levels in the OSCC patients were significantly
      higher than that in the healthy or in the OPMD group. Moreover, the elevated
      levels of salivary RETN were highly correlated with late-stage primary tumors,
      advanced overall stage, and lymph-node metastasis. Our results not only reveal
      that profiling of saliva proteome is feasible for discovery of OSCC biomarkers,
      but also identify RETN as a potential salivary biomarker for OSCC detection.

PMID- 26205616
TI  - Efficacy of Antihypertensive Monotherapies Assessed by Ambulatory Blood Pressure
      Monitoring: Is There Really a Winner?

PMID- 26205621
TI  - Muscle fragments on a scaffold in rats: a potential regenerative strategy in
      urogynecology.
AB  - INTRODUCTION AND HYPOTHESIS: The use of permanent synthetic meshes to improve the
      outcome of pelvic organ prolapse (POP) repair causes frequent and serious
      complications. The use of the synthetic, biodegradable scaffold
      methoxypolyethyleneglycol-polylactic-co-glycolic acid (MPEG-PLGA) seeded with
      autologous muscle fiber fragments (MFF), as an adjunct to native tissue POP
      repair, is a potential new alternative. METHODS: A rat abdominal wall model of
      native repair was used with six animals in each of three groups: native repair,
      native repair + MPEG-PLGA, and native repair + MPEG-PLGA + MFF. MFF were labeled
      with PKH26-fluorescence dye. After 8 weeks labeled cells were identified in
      tissue samples and histopathological and immunohistochemical analyses of
      connective tissue organization and desmin reactivity of muscle cells were
      performed. Fresh tissue samples were subjected to uniaxial biomechanical testing.
      Statistical analyses were performed using one-way analysis of variance (ANOVA).
      RESULTS: MPEG-PLGA was fully degraded after 8 weeks. Desmin-immunopositive (6/6)
      and PKH26-positive cells (6/6) were found only after native repair + MPEG-PLGA +
      MFF, indicating survival, proliferation, and integration of cells originating
      from the MFF. This group also showed significantly increased stiffness in the
      high stiffness zone compared with native repair + MPEG-PLGA (p = 0.032) and
      borderline significantly higher stiffness compared to native repair (p = 0.054).
      CONCLUSIONS: In this pilot study, MPEG-PLGA scaffolds seeded with autologous MFF
      affected some histological and biomechanical properties of native tissue repair
      in an abdominal wall defect model in rats. The method thus appears to be a simple
      tissue engineering concept with potential relevance for native tissue repair of
      POP.

PMID- 26205623
TI  - Interaction of P-glycoprotein with anti-tumor drugs: the site, gate and pathway.
AB  - Understanding the mechanism and pathway of anti-cancer drugs to be pumped out by
      P-glycoprotein (P-gp) in cancer cell is very important for the successful
      chemotherapy. P-gp is a member of ATP-binding cassette (ABC) transporters. In
      this study, random accelerated molecular dynamics (RAMD) simulation was used to
      explore the potential egress pathway of ligands from the binding pocket. This
      could be considered as a reverse process of drug binding. The most possible
      portal of drugs to dissociate is TM4/TM6, which is almost the same for different
      drugs, such as paclitaxel and doxorubicin. The interactions in the binding site
      are found to be remarkably stronger than that outside of the binding site. The
      results were suggested by the free energy calculation between P-gp and different
      drugs from metadynamics simulation. All the results indicate that the flexibility
      of inner residues, especially the residue Phe339, is very important for the drugs
      to access the binding site. 

PMID- 26205622
TI  - Distinctive genotypes in infants with T-cell acute lymphoblastic leukaemia.
AB  - Infant T-cell acute lymphoblastic leukaemia (iT-ALL) is a very rare and poorly
      defined entity with a poor prognosis. We assembled a unique series of 13 infants
      with T-ALL, which allowed us to identify genotypic abnormalities and to
      investigate prenatal origins. Matched samples (diagnosis/remission) were analysed
      by single nucleotide polymorphism-array to identify genomic losses and gains. In
      three cases, we identified a recurrent somatic deletion on chromosome 3. These
      losses result in the complete deletion of MLF1 and have not previously been
      described in T-ALL. We observed two cases with an 11p13 deletion (LMO2-related),
      one of which also harboured a deletion of RB1. Another case presented a large
      11q14.1-11q23.2 deletion that included ATM and only five patients (38%) showed
      deletions of CDKN2A/B. Four cases showed NOTCH1 mutations; in one case FBXW7 was
      the sole mutation and three cases showed alterations in PTEN. KMT2A
      rearrangements (KMT2A-r) were detected in three out of 13 cases. For three
      patients, mutations and copy number alterations (including deletion of PTEN)
      could be backtracked to birth using neonatal blood spot DNA, demonstrating an in
      utero origin. Overall, our data indicates that iT-ALL has a diverse but
      distinctive profile of genotypic abnormalities when compared to T-ALL in older
      children and adults. 

PMID- 26205624
TI  - Effects of Novel ncRNA Molecules, p15-piRNAs, on the Methylation of DNA and
      Histone H3 of the CDKN2B Promoter Region in U937 Cells.
AB  - Non-coding RNAs (ncRNAs) play key roles in epigenetic events. However, the exact
      mechanism of ncRNA guidance, particularly piwi-interacting RNAs (piRNAs), for the
      targeting of epigenetic regulatory factors to specific gene regions is unclear.
      Although piRNA function was first established in germ-line cells, piRNA may be
      crucial in cancer cells. This study investigated the potential roles of CDKN2B
      related piRNA in leukemia cells to provide a potential tumorigenesis model of
      leukemia. CDKN2B-related piRNAs, hsa_piR_014637 and hsa_piR_011186 were
      transduced into the leukemia cell line U937 to study the effect of these two
      piRNAs on cell-cycle progression, apoptosis, heterochromatin formation, CDKN2B
      methylation and expression. Our results show that over-expressing hsa_piR_011186
      promoted cell-cycle progression and decreased apoptosis. We also observed
      inhibition of CDKN2B gene expression. These effects were likely mediated by novel
      piRC (piRNA complex) of CDKN2B-related piRNA that associate with DNMT1, Suv39H1
      and/or EZH2 proteins to modulate the methylation of DNA and histone H3 in the
      promoter region of the CDKN2B gene. The novel piRC complex facilitated epigenetic
      modifications on the promoter of cell-cycle regulating genes, providing an
      expanded view of the role of piRNA in the progression of leukemia cells.

PMID- 26205625
TI  - Triggering nanoparticle surface ligand rearrangement via external stimuli: light
      based actuation of biointerfaces.
AB  - Bio-molecular non-covalent interactions provide a powerful platform for material
      specific self-organization in aqueous media. Here, we introduce a strategy that
      integrates a synthetic optically-responsive motif with a materials-binding
      peptide to enable remote actuation. Specifically, we linked a photoswitchable
      azobenzene moiety to either terminus of a Au-binding peptide. We employed these
      hybrid molecules as capping agents for synthesis of Au nanoparticles. Integrated
      experiments and molecular simulations showed that the hybrid molecules maintained
      both of their functions, i.e. binding to Au and optically-triggered
      reconfiguration. The azobenzene unit was optically switched reversibly between
      trans and cis states while adsorbed on the particle surface. Upon switching, the
      conformation of the peptide component of the molecule also changed. This
      highlights the interplay between the surface adsorption and conformational
      switching that will be pivotal to the creation of actuatable nanoparticle bio
      interfaces, and paves the way toward multifunctional peptide hybrids that can
      produce stimuli responsive nanoassemblies. 

PMID- 26205626
TI  - Stereoselective Synthesis of alpha-3-Deoxy-D-manno-oct-2-ulosonic Acid (alpha
      Kdo) Glycosides Using 5,7-O-Di-tert-butylsilylene-Protected Kdo Ethyl
      Thioglycoside Donors.
AB  - An efficient methodology for the synthesis of alpha-Kdo glycosidic bonds has been
      developed with 5,7-O-di-tert-butylsilylene (DTBS) protected Kdo ethyl
      thioglycosides as glycosyl donors. The approach permits a wide scope of acceptors
      to be used, thus affording biologically significant Kdo glycosides in good to
      excellent chemical yields with complete alpha-selectivity. The synthetic utility
      of an orthogonally protected Kdo donor has been demonstrated by concise
      preparation of two alpha-Kdo-containing oligosaccharides. 

PMID- 26205627
TI  - Current treatment of hepatitis B virus infections.
AB  - Chronic hepatitis B virus (HBV) infection remains an important global burden with
      an estimated 240 million HBV carriers worldwide and more than half a million
      people dying annually from the consequences of the HBV infection. Besides
      interferon and pegylated interferon, there are five antiviral drugs [lamivudine,
      adefovir (dipivoxil), entecavir, telbivudine, and tenofovir disoproxil fumarate]
      that have proved effective in the treatment of chronic hepatitis B. These five
      antiviral drugs interfere with viral DNA synthesis, which consists of a step
      reminiscent of the reverse transcriptase step in the replicative cycle of HIV.
      None of the antiviral drugs, or interferon, are capable of eradicating the
      covalently closed circular DNA, which remains settled as an episome within the
      virus-infected hepatocytes. In the short-term (1-3 years), the use of antiviral
      treatment is aimed at reducing viral DNA below levels of detection, whereas in
      the long term (10 years and, possibly, lifelong), treatment is aimed at reducing
      the progression to cirrhosis, hepatocellular carcinoma, liver decompensation, and
      death. As long as the virus can hide as the episomal covalently closed circular
      DNA, attempts to envisage a definite cure of the HBV infection may seem
      fortuitous.

PMID- 26205628
TI  - Serum DHEAS levels are associated with the development of depression.
AB  - The aim of study was to evaluate the association between serum DHEAS levels and
      depression with a case-control study together with a meta-analysis.
      Radioimmunoassay (RIA) was performed to measure the serum DHEAS levels of all
      participants before and after treatment. Depression Patients were divided into
      mild depression and severe depression based on Hamilton depression scale (HAMD24)
      and received 5-hydroxytryptamine (5-HT) and citalopram (20mg/d) for 8 weeks. Case
      control studies related to our study theme were enrolled for meta-analysis and
      Comprehensive Meta-analysis 2.0 (CMA 2.0) was used for statistical analysis.
      After treatment, DHEAS levels in depression patients were significantly
      increased, while before and after treatment, DHEAS levels were all lower in
      depression patients than in controls (all P<0.001); further analysis on age
      revealed that DHEAS levels were decreased with the rising of age. Meta-analysis
      results suggested that serum DHEAS levels (ng/mL) were significantly higher in
      healthy controls compared to depression patients (SMD=0.777, 95%CI=0.156-1.399,
      P=0.014). In conclusion, our study suggests that serum DHEAS levels are
      associated with the development of depression and it decreased with the rising of
      age. 

PMID- 26205629
TI  - Evaluation of psychiatric and genetic risk factors among primary relatives of
      suicide completers in Delhi NCR region, India.
AB  - Suicide as a public health problem is studied worldwide and association of
      psychiatric and genetic risk factors for suicidal behavior are the point of
      discussion in studies across different ethnic groups. The present study is aimed
      at evaluating psychiatric and genetic traits among primary relatives of suicide
      completer families in an urban Indian population. Bi-variate analysis shows
      significant increase in major depression (PHQ and Hamilton), stress, panic
      disorder, somatoform disorder and suicide attemptamong primary compared to other
      relatives. Sib pair correlations also reveal significant results for major
      depression (Hamilton), stress, suicide attempt, intensity of suicide ideation and
      other anxiety syndrome. 5-HTTLPR, 5-HTT (Stin2) and COMT risk alleles are higher
      among primary relatives, though statistically insignificant. Backward conditional
      logistic regression analysis show only independent variable, Depression
      (Hamilton) made a unique statistically significant contribution to the model in
      primary relatives. 

PMID- 26205630
TI  - Anxiety sensitivity and mindful attention in terms of anxiety and depressive
      symptoms and disorders among Latinos in primary care.
AB  - The present investigation examined the interactive effects of anxiety sensitivity
      and mindful attention in relation to anxiety and depressive symptoms and
      psychopathology among 145 adult Latinos (85.5% female; Mage=39.9, SD=10.8 and
      98.6% used Spanish as their first language) who attended a community-based
      primary healthcare clinic. As expected, the interaction between anxiety
      sensitivity and mindful attention was significantly related to number of mood and
      anxiety disorders, social anxiety, and depressive symptoms. No significant
      interaction, however, was evident for panic (anxious arousal) symptoms. The form
      of the significant interaction indicated that Latinos reporting co-occurring
      higher levels of anxiety sensitivity and lower levels of mindful attention
      evinced the greatest levels of anxiety/depressive psychopathology, social
      anxiety, and depressive symptoms. These data provide novel empirical evidence
      suggesting that there is clinically-relevant interplay between anxiety
      sensitivity and mindful attention in regard to a relatively wide array of anxiety
      and depressive variables among Latinos in a primary care medical setting. 

PMID- 26205631
TI  - Temperament and character personality profile and affective temperaments in self
      poisoning nonlethal suicide attempters.
AB  - Involvement of personality traits in susceptibility to suicidal behaviour has
      attracted considerable research interest over the past decades. This study was
      motivated by reports that emotionality may play a potentially confounding role in
      the association between the personality profile and suicidal behaviour. We
      assessed the association between personality traits, as measured using the
      Temperament and Character Inventory (TCI), and suicidal behaviour, while
      controlling for the effects of Affective Temperaments, measured using the
      Temperament Evaluation of the Memphis, Pisa, Paris and San Diego auto
      questionnaire (TEMPS-A) in a sample of 140 consecutive self-poisoning nonlethal
      suicide (SNS) attempters admitted to the Emergency Toxicology Clinic, comparing
      them with a sample of 140 age and sex matched healthy controls. After controlling
      for Affective Temperaments, the temperament dimension of Novelty Seeking (NS) and
      the character dimensions of Self-directedness and Self-transcendence remained
      significantly associated with SNS attempts. NS, in particular, was most
      consistently and uniquely associated with suicidal behaviour. The present study
      conveys the difficulty in disentangling the personality profile of SNS attempters
      from their emotionality. We conclude that the risk associated with certain
      personality traits is often entirely mediated by Affective Temperaments and few
      dimensions independently contribute to the risk of self-poisoning nonlethal
      suicidal behaviour. 

PMID- 26205632
TI  - The impact of comorbidity profiles on clinical and psychosocial functioning in
      childhood anxiety disorders.
AB  - Despite the high rates of comorbidity in pediatric anxiety disorder samples,
      there are few studies that systematically examine differences in clinical and
      psychosocial functioning between different comorbidity profiles. Those that have,
      typically combine youth with comorbid conduct problem and those with comorbid
      ADHD, despite likely differences in the etiology and course of these conditions.
      This study compared the profile of children with a primary anxiety disorder
      without comorbidity to those with different comorbidity profiles in a treatment
      seeking sample of 111 children recruited from community mental health settings.
      Anxiety severity and depressive symptomatology did not vary by comorbidity
      profile. Anxious children without comorbidity had lower levels of attention
      problems, rule breaking, aggressive and externalizing behaviors compared to the
      comorbid ADHD and comorbid conduct problems groups, as well as lower levels of
      functional impairment and social problems. There were some differences in
      clinical phenomenology and psychosocial functioning between the comorbid ADHD and
      comorbid conduct problems groups, with the conduct problems group having higher
      levels of rule breaking, aggressive and externalizing behaviors, as well as
      higher levels of functional impairment, providing preliminary evidence of
      separate clinical profiles. 

PMID- 26205633
TI  - High incidence and increasing prevalence of multiple sclerosis in British
      Columbia, Canada: findings from over two decades (1991-2010).
AB  - Province-wide population-based administrative health data from British Columbia
      (BC), Canada (population: approximately 4.5 million) were used to estimate the
      incidence and prevalence of multiple sclerosis (MS) and examine potential trends
      over time. All BC residents meeting validated health administrative case
      definitions for MS were identified using hospital, physician, death, and health
      registration files. Estimates of annual prevalence (1991-2008), and incidence
      (1996-2008; allowing a 5-year disease-free run-in period) were age and sex
      standardized to the 2001 Canadian population. Changes over time in incidence,
      prevalence and sex ratios were examined using Poisson and log-binomial
      regression. The incidence rate was stable [average: 7.8/100,000 (95 % CI 7.6,
      8.1)], while the female: male ratio decreased (p = 0.045) but remained at or
      above 2 for all years (average 2.8:1). From 1991-2008, MS prevalence increased by
      4.7 % on average per year (p < 0.001) from 78.8/100,000 (95 % CI 75.7, 82.0) to
      179.9/100,000 (95 % CI 176.0, 183.8), the sex prevalence ratio increased from
      2.27 to 2.78 (p < 0.001) and the peak prevalence age range increased from 45-49
      to 55-59 years. MS incidence and prevalence in BC are among the highest in the
      world. Neither the incidence nor the incidence sex ratio increased over time.
      However, the prevalence and prevalence sex ratio increased significantly during
      the 18-year period, which may be explained by the increased peak prevalence age
      of MS, longer survival with MS and the greater life expectancy of women compared
      to men.

PMID- 26205634
TI  - Does treatment with t-PA increase the risk of developing epilepsy after stroke?
AB  - Patients suffering from ischemic stroke carry an enhanced risk of developing
      secondary epilepsy. We sought to clarify whether thrombolytic treatment with
      recombinant tissue plasminogen activator (t-PA) is independently associated with
      post-stroke epilepsy (PSE). In this observational study, data from 302 stroke
      patients treated at a single academic neurological department were analyzed
      retrospectively. Median follow-up was 42 months (maximum 80). Variables included
      presence of comorbidity, stroke severity, neurological presentation,
      complications, infarct characteristics, and treatment with t-PA. After univariate
      analyses, a multivariate analysis was performed to create a model of factors that
      were significantly associated with PSE, including treatment with t-PA. 13.9 % of
      patients developed PSE during follow-up. Multivariate analysis identified 5
      independent factors for PSE: low Barthel Index at discharge; hemianopia;
      infection acquired during the hospital stay; involvement of the temporal lobe;
      involvement of the perirolandic cortex. While the incidence of PSE was higher in
      patients treated with t-PA (20.6 vs. 10.7 %, univariate analysis; p = 0.020), the
      effect was lost after adjusting for several factors associated with t-PA
      treatment [odds ratio for PSE after treatment with t-PA 1.3 (95 % CI 0.6-2.9), p
      = 0.489]. This study failed to identify treatment with t-PA as an independent
      risk factor for PSE.

PMID- 26205635
TI  - Brain MRI lesions and atrophy are associated with employment status in patients
      with multiple sclerosis.
AB  - Multiple sclerosis (MS) commonly affects occupational function. We investigated
      the link between brain MRI and employment status. Patients with MS (n = 100)
      completed a Work Productivity and Activity Impairment (WPAI) (general health
      version) survey measuring employment status, absenteeism, presenteeism, and
      overall work and daily activity impairment. Patients "working for pay" were
      considered employed; "temporarily not working but looking for work," "not working
      or looking for work due to age," and "not working or looking for work due to
      disability" were considered not employed. Brain MRI T1 hypointense (T1LV) and T2
      hyperintense (T2LV) lesion volumes were quantified. To assess lesional
      destructive capability, we calculated each subject's ratio of T1LV to T2LV
      (T1/T2). Normalized brain parenchymal volume (BPV) assessed brain atrophy. The
      mean (SD) age was 45.5 (9.7) years; disease duration was 12.1 (8.1) years; 75 %
      were women, 76 % were relapsing-remitting, and 76 % were employed. T1LV, T1/T2,
      Expanded Disability Status Scale (EDSS) scores, and activity impairment were
      lower and BPV was higher in the employed vs. not employed group (Wilcoxon tests,
      p < 0.05). Age, disease duration, MS clinical subtype, and T2LV did not differ
      between groups (p > 0.05). In multivariable logistic regression modeling,
      adjusting for age, sex, and disease duration, higher T1LV predicted a lower
      chance of employment (p < 0.05). Pearson correlations showed that EDSS was
      associated with activity impairment (p < 0.05). Disease duration, age, and MRI
      measures were not correlated with activity impairment or other WPAI outcomes (p >
      0.05). We report a link between brain atrophy and lesions, particularly lesions
      with destructive potential, to MS employment status.

PMID- 26205637
TI  - Effect of peritoneal incision on immediate pain after inguinal hernia repair: A
      Prospective Cohort Study.
AB  - OBJECTIVE: Hernia repair is a common surgical procedure, and postoperative pain
      is an inevitable result of hernia surgery. The prevention of postoperative pain
      is of considerable importance in terms of patient comfort and early discharge. In
      this study, we evaluated the effects of a peritoneal incision on pain in the
      early postoperative period. SUMMARY OF BACKGROUND DATA: This was a prospective
      clinical study with 75 patients undergoing inguinal hernia repair. METHODS:
      Patients were divided into five groups: group 1: indirect hernia, Lichtenstein
      repair with peritoneal incision, group 2: indirect hernia, Lichtenstein repair
      without peritoneal incision, group 3: all hernias, trans-abdominal
      preperitoneal(TAPP) repair, group 4: all hernias, total extraperitoneal (TEP)
      repair, and group 5: direct hernia, Lichtenstein repair with no peritoneal
      incision. Groups were compared in terms of postoperative pain scores at three
      different times and complications. RESULTS: There were 62 males and 13 females;
      their average age was 51.25 years. The visual analog scale (VAS) scores were
      lower in groups 2, 4, and 5, and there were differences among groups and within
      each group according to VAS changes assessed at all time points (p < 0.05). There
      was no difference, according to VAS analysis, between open and laparoscopic
      surgery groups. There was a difference according to VAS changes in each group
      between hernia sides (p < 0.001). CONCLUSION: Peritoneal incision is a
      significant risk factor for postoperative pain after inguinal hernia repair. But,
      surgical procedure was not a risk factor although VAS scores were higher in open
      than laparoscopic surgery.

PMID- 26205636
TI  - Childhood-Onset Anti-Ku Antibody-Positive Generalized Morphea with Polymyositis:
      A Japanese Case Study.
AB  - We report a 16-year-old Japanese girl with anti-Ku antibody-positive generalized
      morphea and polymyositis who, at the age of 7 years, developed multiple brownish
      plaques on her left forearm that gradually extended to her upper arm, back, and
      left thigh, which a skin biopsy revealed as morphea. Laboratory testing was
      positive for antinuclear antibody and a high serum creatine kinase level.
      Although there were no clinical signs of muscular involvement, magnetic resonance
      imaging revealed findings consistent with myositis. The patient is one of the
      youngest reported cases positive for anti-Ku antibody. Anti-Ku positivity
      concomitant with generalized morphea is rare. 

PMID- 26205638
TI  - Functional gadoxetate disodium-enhanced MRI in patients with primary sclerosing
      cholangitis (PSC).
AB  - OBJECTIVES: To assess the value of variable flip angle-based T1 liver mapping on
      gadoxetate disodium-enhanced MRI in patients with primary sclerosing cholangitis
      (PSC) for evaluation of global and segmental liver function, and determine a
      possible correlation with disease severity. METHODS: Sixty-one patients (19
      female, 42 male; mean age 41 years) with PSC were included in this prospective
      study. T1 mapping was performed using a 3D-spoiled GRE sequence (flip angles 5
      degrees , 15 degrees , 20 degrees , 30 degrees ) before, 16 (HP1) and 132 min
      (HP2) after contrast injection. T1 values were measured and compared (Wilcoxon
      Test) by placing ROIs in each liver segment. The mean reduction of T1 relaxation
      time at HP1 and HP2 was calculated and correlated with liver function tests
      (LFTs), MELD, Mayo Risk and Amsterdam Scores (Spearman correlation). RESULTS:
      Significant changes of T1 relaxation times between non-enhanced and gadoxetate
      disodium-enhanced MRI at HP1 and HP2 could be observed in all liver segments (p <
      0.0001). A significant correlation of T1 reduction could be observed with LFTs,
      MELD and Mayo Risk Score (p < 0.05). CONCLUSIONS: T1 mapping of the liver using a
      variable flip angle-based sequence is a feasible technique to evaluate liver
      function on a global level, and may be extrapolated on a segmental level in
      patients with PSC. KEY POINTS: * T1 mapping enables evaluation of global liver
      function in PSC. * T1 relaxation time reduction correlates with the MELD and
      MayoRisk Score. * Extrapolated, T1 mapping may allow for segmental evaluation of
      liver function.

PMID- 26205639
TI  - Isometric stress in cardiovascular magnetic resonance-a simple and easily
      replicable method of assessing cardiovascular differences not apparent at rest.
AB  - INTRODUCTION: Isometric exercise may unmask cardiovascular disease not evident at
      rest, and cardiovascular magnetic resonance (CMR) imaging is proven for
      comprehensive resting assessment. This study devised a simple isometric exercise
      CMR methodology and assessed the hemodynamic response evoked by isometric
      exercise. METHODS: A biceps isometric exercise technique was devised for CMR, and
      75 healthy volunteers were assessed at rest, after 3-minute biceps exercise, and
      5-minute of recovery using: 1) blood pressure (BP) and 2) CMR measured aortic
      flow and left ventricular function. Total peripheral resistance (SVR) and
      arterial compliance (TAC), cardiac output (CO), left ventricular volumes and
      function (ejection fraction, stroke volume, power output), blood pressure (BP),
      heart rate (HR), and rate pressure product were assessed at all time points.
      RESULTS: Image quality was preserved during stress. During exercise there were
      increases in CO (+14.9 %), HR (+17.0 %), SVR (+9.8 %), systolic BP (+22.4 %),
      diastolic BP (+25.4 %) and mean BP (+23.2 %). In addition, there were decreases
      in TAC (-22.0 %) and left ventricular ejection fraction (-6.3 %). Age and body
      mass index modified the evoked response, even when resting measures were similar.
      CONCLUSIONS: Isometric exercise technique evokes a significant cardiovascular
      response in CMR, unmasking physiological differences that are not apparent at
      rest. KEY POINTS: * Isometric exercise unmasks cardiovascular differences not
      evident at rest. * CMR is the reference standard for non-invasive cardiovascular
      assessment at rest. * A new easily replicable method combines isometric exercise
      with CMR. * Significant haemodynamic changes occur and differences are unmasked.
      * The physiological, isometric CMR stressor can be easily replicated.

PMID- 26205640
TI  - Quality of systematic reviews: an example of studies comparing artificial disc
      replacement with fusion in the cervical spine.
AB  - Cervical artificial disc replacement (C-ADR) is now an alternative to anterior
      cervical discectomy and fusion (ACDF). Many studies have evaluated the efficacy
      of C-ADR compared with ACDF. This led to a series of systematic reviews and meta
      analyses to evaluate the evidence of the superiority of one intervention against
      the other. The aim of the study presented here was to evaluate the quality of
      these reviews and meta-analyses. Medline via Ovid, Embase, and Cochrane Library
      were searched using the keywords: (total disk replacement, prosthesis,
      implantation, discectomy, and arthroplasty) AND (cervical vertebrae, cervical
      spine, and spine) AND (systematic reviews, reviews, and meta-analysis). Screening
      and data extraction were conducted by two reviewers independently. Two reviewers
      then assessed the quality of the selected reviews and meta-analysis using 11-item
      AMSTAR score which is a validated measurement tool to assess the methodological
      quality of systematic reviews. Screening of full reports of 46 relevant abstracts
      resulted in the selection of 15 systematic reviews and/or meta-analyses as
      eligible for this study. The two reviewers' inter-rater agreement level was high
      as indicated by kappa of >0.72. The AMSTAR score of the reviews ranged from 3 to
      11. Only one study (a Cochrane review) scored 100% (AMSTAR 11). Five studies
      scored below (AMSTAR 5) indicating low-quality reviews. The most significant
      drawbacks of reviews of a score below 5 were not using an extensive search
      strategy, failure to use the scientific quality of the included studies
      appropriately in formulating a conclusion, not assessing publication bias, and
      not reporting the excluded studies. With a significant exception of a Cochrane
      review, the methodological quality of systematic reviews evaluating the evidence
      of C-ADR versus ACDF has to be improved. 

PMID- 26205641
TI  - Investigation of urban ethnoveterinary in three veterinary clinics at east zone
      of Sao Paulo city, Brazil.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Urban Ethnoveterinary should be further explored
      because of its value as it resists conventional medical care. In addition, the
      comparison between the resources used by Ethnoveterinary and Ethnopharmacology
      should be investigated in depth, increasing the availability of new bioactive
      potential in human and veterinary medicines. This project aimed to determine
      whether plants are used in the health care of dogs and/or cats in urban area and
      to compare its uses with other ethnoveterinary and ethnopharmacological data.
      MATERIALS AND METHODS: Three veterinary clinics from east area of Sao Paulo city
      were selected, in order to record the offering of plants to pets by their owners.
      Individual interviews were conducted from May to November 2012 and consisted of
      application of semi-structured interviews and questionnaires. A literature search
      was performed to compare our findings with other ethnopharmacological and
      ethnoveterinarian data from the literature. RESULTS: A total of 273 people were
      interviewed and 46 (16.84%) of them utilize medicinal plants for their pets. Most
      plant species are exclusively home grown (57.9%). The plants most cited were
      Plectranthus barbatus Andrews, Matricaria chamomilla L. and Foeniculum vulgare
      Mill. The most frequent route of administration, part utilized and mode of
      preparation was oral (80.35%), leaves (89.47%) and infusion (61.90%),
      respectively. From 19 cited plants, 14 (73.7%) are mentioned in ethnoveterinary
      literature, whereas 11 (57.9%) are used for the same purposes. All plants
      reported in our study have at least one common use with ethnopharmacology.
      CONCLUSION: The survey provided evidence of ethnoveterinary use of medicinal
      plants for dogs and/or cats in urban area of Sao Paulo, complementarily with the
      official veterinary, and showed that the plants used in pets are also used in
      humans with the same purposes and routes of administration, as well as in other
      animals.

PMID- 26205642
TI  - Chloral Hydrate Preconditioning Protects Against Ischemic Stroke via Upregulating
      Annexin A1.
AB  - AIMS: Preconditioning is promising for treating cerebral ischemic stroke. Annexin
      A1 (ANXA1) is a homeostatic antiinflammatory mediator that participates in
      countering against ischemic injuries. We investigated whether chloral hydrate
      preconditioning (CH) exerts neuroprotection via regulation of ANXA1 in stroke.
      METHODS: Adult male C57BL/6J mice or ANXA1 knockout (ANXA1(-/-) ) mice were
      randomly allocated to control (NCH) and CH groups [2%, 6%, and 10% chloral
      hydrate (i.p.) 1 h before the middle cerebral artery occlusion (MCAO)].
      Neurological performances were evaluated by modified 7-point neurological scales
      and rotarod test. Cerebral infarction was analyzed by triphenyltetrazolium
      chloride (TTC) staining and MRI. The expression of ANXA1, pro-inflammatory (TNF
      alpha, IL-1beta, IL-6), and antiinflammatory (IL-4, IL-10, TGF-beta) cytokines
      was investigated by RT-PCR, western blot, and immunofluorescence. RESULTS:
      Chloral hydrate preconditioning significantly improved the neurological outcomes
      and reduced the infarction and brain edema after ischemia. In addition, CH
      increased the expression of ANXA1 in the microglia, decreased the levels of TNF
      alpha, IL-1beta, and IL-6, while elevated the levels of IL-4, IL-10, and TGF-beta
      in the MCAO mice. Furthermore, both ANXA1 blocker Boc1 (5 mg/kg, i.c.v.) or ANXA1
      gene deficiency restrained the protective effects of CH against stroke.
      CONCLUSIONS: Chloral hydrate preconditioning protects against ischemic injuries
      through upregulating the expression of ANXA1, and the followed antiinflammatory
      mechanisms.

PMID- 26205643
TI  - Aggression in US soldiers post-deployment: Associations with combat exposure and
      PTSD and the moderating role of trait anger.
AB  - Anger and aggression are among the most common issues reported by returning
      service members from combat deployments. However, the pathways between combat
      exposure and anger and aggression have not been comprehensively characterized.
      The present study aimed to characterize the relationship between trait anger,
      combat exposure, post-deployment PTSD, and aggression. U.S. Army soldiers (N =
      2,420) were administered anonymous surveys assessing combat exposure, current
      PTSD symptoms and aggression, as well as trait anger items 3 months after
      returning from deployment to Afghanistan. PTSD symptom levels were related to
      aggression at higher levels of trait anger, but not evident among soldiers who
      had lower levels of trait anger. The pathway from combat exposure to PTSD, and
      then to aggression, was conditional upon levels of trait anger, such that the
      pathway was most evident at high levels of trait anger. This was the first study
      to our knowledge that concurrently modeled unconditional and conditional direct
      and indirect associations between combat exposure, PTSD, trait anger, and
      aggression. The findings can be helpful clinically and for developing screening
      protocols for combat exposed Soldiers. The results of this study suggest the
      importance of assessing and managing anger and aggression in soldiers returning
      from combat deployment. Anger is one of the most common complaints of returning
      soldiers and can have debilitating effects across all domains of functioning. It
      is imperative that future research efforts are directed toward understanding this
      phenomenon and developing and validating effective treatments for it.

PMID- 26205644
TI  - Propofol Provides More Effective Protection for Circulating Lymphocytes Than
      Sevoflurane in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery.
AB  - OBJECTIVES: To compare the effects of propofol, sevoflurane, and the combination
      of the 2 on circulating lymphocytes in patients undergoing off-pump coronary
      artery bypass graft (OPCAB) surgery. DESIGN: A prospective, randomized study.
      SETTING: A university hospital. PARTICIPANTS: One hundred five patients
      undergoing elective OPCAB surgery. INTERVENTIONS: Participants were randomized to
      receive sevoflurane (group S), propofol (group P), or coadministration (group C)
      of sevoflurane- and propofol-maintained anesthesia. MEASUREMENTS AND MAIN
      RESULTS: Blood samples were obtained before, during, and after surgery. Caspase-3
      and apoptosis-inducing factor in lymphocytes were evaluated by Western blot.
      During surgery, 5 minutes after revascularization of the left anterior descending
      artery, 5 minutes after all anastomoses (T4), and after the sternal closure (T5),
      caspase-3 expression of group S was higher than that of group P (p = 0.02) and
      group C (p = 0.02). At T4 and T5, expression of active apoptosis-inducing factor
      in group S was higher than that in the other 2 groups (p = 0.03 and p = 0.04,
      respectively). 24 hours after surgery, the lymphocyte count of group S (0.55/nL)
      was lower than that of group P (0.73/nL, p = 0.02) and group C (0.73/nL, p =
      0.03). Intensive care unit stay of group S (3.0 days) was longer than that of the
      other 2 groups (2.2 days, p = 0.02 and 2.1 days, p = 0.01). CONCLUSIONS: OPCAB
      surgery was associated with postoperative lymphopenia. Regarding a protective
      effect for circulating lymphocytes, propofol and the combination of sevoflurane-
      and propofol-maintained anesthesia were both superior to sevoflurane-maintained
      anesthesia.

PMID- 26205645
TI  - Breast Cancer Cells are in Biopsy Channel in Postoperative Material from
      Mastectomies Preformed 3 days after Core Needle Biopsy (CNB) but They Do Not
      Persist at Biopsy Channel Apart from the Tumor after 10 Days from the CNB
      Procedure-a Study of seven Cases.

PMID- 26205646
TI  - Incidental thyroid lesions on FDG-PET/CT: a prevalence study and proposition of
      management.
AB  - AIM: Thyroid incidentaloma is defined as an unsuspected, asymptomatic thyroid
      lesion that is discovered on an imaging study. The purpose of this study is to
      determine incidentally identified thyroid lesions by FDG-PET/CT in cancer
      patients by virtue of preoperative staging and to pay attention how should be the
      management of these patients with thyroid lesion. METHODS: From January 2011 to
      January 2013, 2654 patients underwent FDG-PET/CT in our institution. Among them,
      34 patients had thyroid incidentaloma. All patients underwent ultrasonographic
      (US) examination. If there is a nodul, fine needle aspirations (FNA) were
      performed to these patients. We did not perform FNA to patients who had diffuse
      thyroid uptake. Patients were divided into two groups; malign and non-malign
      patients according to FNA histo-pathologic results. Group 1 (N.=11) diagnosed
      malignancy in histo-pathologic evaluation, group 2 (N.=23) could not diagnosed
      malignancy in histo-pathologic, clinic and radiologic evaluation. These two
      groups were compared statistically in terms of SUV max levels that reached in PET
      examinations. RESULTS: Incidentally thyroid lesions were found in 34 patients in
      the course of FDG-PET/CT examination (25 females and 9 males), mean age 57.7
      years. Nodular goitre in 12 patients, hyperthyroidism in 2 patients, sub-clinic
      hyperthyroidism in 3 patients and hashimoto thyroiditis in 6 patients were
      diagnosed in non-malignancy group (Group-2). Group 1 included 11 patients with
      incidentally diagnosed thyroid malignancy. 11 patients malignancy diagnoses were
      verified by FNA and 9 of them were operated. In PET evaluation thyroid up-take
      was diffuse in 9 patients, at left lob in 12 patients and at right lop in 13
      patients. When we compared the groups according to SUV max levels; we found that
      malignant thyroid lesions had a significantly higher (P<0.001) SUVmax than benign
      thyroid lesions. A cut off SUVmax value (>6.2) was found in the study.
      CONCLUSION: The incidental finding of focal thyroid uptake on FDG-PET scanning
      has an elevated malignancy risk from other thyroid nodules. According to our
      knowledge diagnose, treatment and follow-up of these patients should be in
      multidiscipliner approach. Oncology, endocrinology, endocrine surgeon,
      interventional radiology, pathology and psychiatry should be gathered in
      multidiscipliner team. For these reason these patients need more careful
      evaluation.

PMID- 26205647
TI  - Results of a national multicentric study on compliance to treatment with various
      disphosphonate formulations in patients with postmenopausal osteoporosis.
AB  - AIM: Compliance to pharmacological treatment for osteoporosis is crucial if the
      risk of fracture is to be reduced. Case series show that treatment with
      traditional bisphosphonates in the form of tablets has a compliance of between
      approximately 30% and 70%. The aims of this paper were to assess compliance to
      treatment with various formulations of bisphonates and to identify those at
      highest risk of discontinuation. METHODS: In this multicentre retrospective
      observational study, a population of 387 women diagnosed with postmenopausal
      osteoporosis under treatment with bisphosphonates (risedronate, ibandronate,
      alendronate in tablet form, alendronate in a fluid solution per os) was observed
      for at least a year. Demographic data and information pertaining to the type of
      drug taken, compliance to treatment, side effects, reasons for discontinuation,
      the basal examination and follow-up at 18 months and later were recorded. RESULTS
      AND CONCLUSION: Analysis of patient compliance to a prescribed treatment plan
      showed a significantly higher persistence (P<0.001) in the group taking
      alendronate in soluble solution form (83.3%) compared to the group taking any
      bisphosphonate in tablet form (66.7%). At the same time, patientspresenting
      comorbidity, receiving more than one therapy, not taking vitamin D, and in
      surgical menopause, risked discontinuation.

PMID- 26205648
TI  - Effectiveness and safety of calcium and vitamin D treatment for postmenopausal
      osteoporosis.
AB  - Imbalance of bone resorption and bone formation is responsible for osteoporosis
      that is characterized by decreased bone mass and mineral density. The aim of this
      study was to evaluate the available data that could clarify the effectiveness and
      safety of supplementations with calcium and vitamin D, alone or in combination,
      to slow down bone loss in postmenopausal and elderly women. Using search key
      words, we performed a research both in the PubMed and Cochrane Library in order
      to find all meta-analysis, prospective and randomized clinical studies published
      from 2000 to 2014 that had investigated the effectiveness of calcium and vitamin
      D in the treatment of osteoporosis. At the moment it is not possible either to
      provide reassurance that calcium supplements given with vitamin D do not cause
      adverse cardiovascular events or to link them with certainty to increased
      cardiovascular risk. According to the data now available, vitamin D, at dosage of
      at least 800 IU/day, alone or in combination with antiresorptive drugs, should be
      administered in osteoporotic and osteopenic patients for a primary and secondary
      prevention. Further studies are needed and the debate remains ongoing. However,
      every administration needs the calculation of the absolute fracture risk of the
      patient. Especially considering the high cost of osteoporosis prevention, more
      studies are mandatory to clarify indications and contraindications. 

PMID- 26205649
TI  - Oral cavity cancer trends over the past 25 years in Hong Kong: a multidirectional
      statistical analysis.
AB  - BACKGROUND: Even though oral cavity cancer (OCC; ICD 10 codes C01, C02, C03, C04,
      C05, and C06) ranks eleventh among the world's most common cancers, accounting
      for approximately 2 % of all cancers, a trend analysis of OCC in Hong Kong is
      lacking. Hong Kong has experienced rapid economic growth with socio-cultural and
      environmental change after the Second World War. This together with the collected
      data in the cancer registry provides interesting ground for an epidemiological
      study on the influence of socio-cultural and environmental factors on OCC
      etiology. METHODS: A multidirectional statistical analysis of the OCC trends over
      the past 25 years was performed using the databases of the Hong Kong Cancer
      Registry. The age, period, and cohort (APC) modeling was applied to determine
      age, period, and cohort effects on OCC development. Joinpoint regression analysis
      was used to find secular trend changes of both age-standardized and age-specific
      incidence rates. RESULTS: The APC model detected that OCC development in men was
      mainly dominated by the age effect, whereas in women an increasing linear period
      effect together with an age effect became evident. The joinpoint regression
      analysis showed a general downward trend of age-standardized incidence rates of
      OCC for men during the entire investigated period, whereas women demonstrated a
      significant upward trend from 2001 onwards. CONCLUSIONS: The results suggest that
      OCC incidence in Hong Kong appears to be associated with cumulative risk
      behaviors of the population, despite considerable socio-cultural and
      environmental changes after the Second World War.

PMID- 26205650
TI  - Changing the way pharmacy only drugs are supplied would be unwise.

PMID- 26205651
TI  - Chemical Schemes for Maintaining Different Compositions Across a Semi-permeable
      Membrane with Application to Proto-cells.
AB  - Osmotic pressure arising from a higher total chemical concentration inside proto
      cells is thought to have played a role in the emergence and selection of self
      replicating proto-cells. We present two chemical schemes through which different
      equilibrium compositions can coexist on each side of a semi-permeable membrane.
      The first scheme relies upon the concept of moieties and associated number of
      degrees of freedom. The second scheme relies upon the concept of siphons and of
      pass reaction capable of transferring matter from outside a siphon into it. Using
      simple example reaction networks, we show that both schemes are compatible with
      stationary proto-cell growth with up-concentration, but suffer from shortcomings.
      To alleviate these we propose a third scheme derived from the second one by
      having the pass reaction catalyzed by the membrane surface instead of occurring
      in bulk solution. This may have proven an intermediate step before having the
      pass reaction occurring only when the nutrient crosses the membrane. This
      suggests an evolutionary path for the emergence of active transport. 

PMID- 26205652
TI  - The Activation of Free Dipeptides Promoted by Strong Activating Agents in Water
      Does not Yield Diketopiperazines.
AB  - The activation of dipeptides was studied in the perspective of the abiotic
      formation of oligopeptides of significant length as a requirement for secondary
      structure formation. The formation of piperazin-2,5-diones (DKP), previously
      considered as a dead end when activating free dipeptides, was shown in this work
      to be efficiently suppressed when using strong activating agents (e.g.,
      carbodiimides). This behaviour was explained by the fast formation of a 5(4H)
      oxazolone intermediate at a rate that exceeds the time scale of the rotation of
      the peptide bond from the predominant trans-conformation into the cis-isomer
      required for DKP formation. No DKP was observed when using strong activating
      agents whereas phosphate mixed anhydrides or moderately activated esters were
      observed to predominantly yield DKP. The DKP side-reaction no longer constitutes
      a drawback for the C-terminus elongation of peptides. These results are
      considered as additional evidence that pathways involving strong activation are
      required to drive the emergence of living entities rather than close to
      equilibrium processes. 

PMID- 26205653
TI  - BMP9-induced osteogenic differentiation is partially inhibited by miR-30a in the
      mesenchymal stem cell line C3H10T1/2.
AB  - In the bone morphogenetic protein (BMP) family, BMP9 is the strongest inducer of
      osteogenic differentiation in mesenchymal stem cells. Recent studies have
      suggested that the miR-30 family regulates cell proliferation and osteoblastic
      differentiation. In the present study, we found that expression of only one miR
      30 family member, miR-30a, first decreased and then increased during BMP9-induced
      osteogenic differentiation. Cell proliferation assays revealed that miR-30a had
      no effect on the proliferation of C3H10T1/2 cells. However, over-expression of
      miR-30a led to expression of an early osteogenic marker and a reduction in Runx2
      expression. In addition, we observed decreases in the expression of late
      osteogenic markers and osteopontin, as well as calcium deposition. Dual
      luciferase reporter assays indicated that this process might be mediated by
      suppressing Runx2 protein expression. In vivo stem cell implantation revealed
      inhibition of BMP9-induced ectopic bone formation and matrix mineralization by
      miR-30a. This study provides a better understanding of the molecular mechanisms
      through which miR-30a negatively regulates BMP9-induced osteogenic
      differentiation. 

PMID- 26205654
TI  - Overexpression of transforming growth factor type III receptor restores TGF-beta1
      sensitivity in human tongue squamous cell carcinoma cells.
AB  - The transforming growth factor type III receptor (TbetaRIII), also known as beta
      glycan, is a multi-functional sensor that regulates growth, migration and
      apoptosis in most cancer cells. We hereby investigated the expression of
      TbetaRIII in clinical specimens of tongue squamous cell carcinoma (TSCC) and the
      underlying mechanism that TbetaRIII inhibits the growth of CAL-27 human oral
      squamous cells. The TSCC tissues showed a significant decrease in TbetaRIII
      protein expression as detected by immunohistochemistry (IHC) and western blot
      analysis. Transfection of TbetaRIII-containing plasmid DNA dramatically promoted
      TGF-beta1 (10 ng/ml)-induced decrease in cell viability, apoptosis and cell
      arrest at the G0-/G1-phase. Moreover, transient overexpression of TbetaRIII
      enhanced the TGF-beta1-induced cyclin-dependent kinase inhibitor 2b (CDKN2b) and
      p38 protein activity, but did not affect the activities of extracellular signal
      regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2) in CAL-27
      cells. These results suggest overexpression of TbetaRIII receptor restored TGF
      beta1 sensitivity in CAL-27 cells, which may provide some new insights on
      exploiting this molecule therapeutically. 

PMID- 26205655
TI  - Digital imaging in the immunohistochemical evaluation of the proliferation
      markers Ki67, MCM2 and Geminin, in early breast cancer, and their putative
      prognostic value.
AB  - BACKGROUND: Immunohistochemical assessment of proliferation may provide
      additional prognostic information in early breast cancer. However, due to a lack
      of methodological standards proliferation markers are still not routinely used
      for determining therapy. Even for Ki67, one of the most widely-studied markers,
      disagreements over the optimal cutoff exist. Improvements in digital microscopy
      may provide new avenues to standardise and make data more reproducible. METHODS:
      We studied the immunohistochemical expression of three markers of proliferation:
      Ki67, Mini-Chromosome Maintenance protein 2 and Geminin, by conventional light
      microscope and digital imaging on triplicate TMAs from 309 consecutive cases of
      primary breast cancers. Differences between the average and the maximum
      percentage reactivity in tumour cell nuclei from the three TMA cores were
      investigated to assess the validity of the approach. Time-dependent Receiver
      Operating Characteristic curves were utilized to obtain optimal expression level
      cut-offs, which were then correlated with clinico-pathological features and
      survival. RESULTS: High concordance between conventional and digital scores was
      observed for all 3 markers (Ki67: rs = 0.87, P < 0.001; MCM2: rs = 0.94, P <
      0.001; and Geminin: rs = 0.86, P < 0.001; Spearman's rank). There was no
      significant difference according to the number of TMA cores included for either
      Ki67 or MCM2; analysis of two or three cores produced comparable results. Higher
      levels of all three proliferation markers were significantly associated with
      higher grade (P < 0.001) and ER-negativity (P < 0.001). Optimal prognostic cut
      offs for percentage expression in the tumour were 8 %, 12 and 2.33 % for Ki67,
      MCM2 and Geminin respectively. All 3 proliferation marker cutoffs were predictive
      of 15-year breast cancer-specific survival in univariable Cox regression
      analyses. In multivariable analysis only lymph node status (HR = 3.9, 95 % CI =
      1.79-8.5, P = 0.0006) and histological grade (HR = 1.84, 95 % CI = 1-3.38, P =
      0.05) remained significantly prognostic. CONCLUSIONS: Here we show that. MCM2 is
      a more sensitive marker of proliferation than Ki67 and should be examined in
      future studies, especially in the lymph node-negative, hormone receptor-positive
      subgroup. Further, digital microscopy can be used effectively as a high
      throughput method to evaluate immunohistochemical expression.

PMID- 26205656
TI  - Circulating miRNAs profiles in Tourette syndrome: molecular data and clinical
      implications.
AB  - BACKGROUND: Tourette Syndrome (TS) is a highly prevalent childhood
      neuropsychiatric disorder (about 1 %), characterized by multiple motor and one or
      more vocal tics. The syndrome is commonly associated to comorbid conditions
      (e.g., Attention Deficit Hyperactivity Disorder and Obsessive Compulsive
      Disorder), which considerably aggravate clinical symptoms and complicate
      diagnosis and treatment. To date, TS molecular bases are unknown and its
      molecular diagnosis is unfeasible. RESULTS: Due to their master role within cell
      networks and pathways both in physiology as in pathology, we sought to determine
      the transcriptome of circulating miRNAs in TS patients: by TaqMan Low Density
      Arrays, we profiled the expression in serum of 754 miRNAs in six TS patients and
      three unaffected controls (NCs) (discovery set). These data were validated by
      single TaqMan assays on serum from 52 TS patients and 15 NCs (validation set).
      Network and Gene-ontology analysis were performed by using Cytoscape and
      Babelomics server. We found that miR-429 is significantly underexpressed in TS
      patients with respect to NCs. Decreased serum levels of miR-429 allowed us to
      discriminate TS patients from NCs with 95 % of sensitivity and 42 % of
      specificity. Intriguingly, computational analysis of the network comprising miR
      429 targets demonstrates their involvement in differentiation of midbrain and
      hindbrain and synaptic transmission. CONCLUSIONS: Our data open the way to
      further molecular characterization of TS and eventual identification of the
      corresponding genotypes. Circulating miR-429 may be immediately useful as
      sensitive molecular biomarker to support TS diagnosis, actually based only on DSM
      V criteria.

PMID- 26205657
TI  - Prenatal exposure to perfluroalkyl substances and children's IQ: The Taiwan
      maternal and infant cohort study.
AB  - BACKGROUND: Perfluoroalkyl substances (PFASs) are a group of fluorinated organic
      substances that are widely used in consumer products and are often detectable in
      human tissues. Human studies on prenatal exposure to PFASs and neurodevelopment
      in children are few and inconsistent. METHODS: In the Taiwan Maternal and Infant
      Cohort Study, we collected serum samples from pregnant women during the third
      trimester and measured concentrations of 9 PFASs using a high performance liquid
      chromatography system. A subsample of their children was assessed with full scale
      intelligence quotient (FSIQ), verbal IQ (VIQ) and performance IQ (PIQ) at both
      age 5 (n=120) and 8 years (n=120). We used multivariate linear regression models
      to examine prenatal PFAS exposure in relation to IQ scores at each age period.
      RESULTS: Prenatal perfluoroundecanoic acid (PFUnDA) concentrations were inversely
      associated with children's PIQ scores at age 5 years, with an adjusted
      coefficient (beta) of -1.6 (95% confidence interval [CI]: (-3.0, -0.2). When
      children reached 8 years, most of the prenatal PFASs showed inverse association
      with children's FSIQ, VIQ and PIQ scores. Among them, prenatal perfluorononanoic
      acid (PFNA) reached significance. Children with higher prenatal PFNA levels had
      lower VIQ with an adjusted beta of -2.1 (95% CI: -3.9, -0.2). CONCLUSIONS: We
      found two prenatal PFAS exposure, both long-chain PFASs, in association with
      decreased IQ test scores in children. Our findings suggest more studies on long
      chain PFASs and children's neurodevelopment.

PMID- 26205658
TI  - Envenomation by caterpillars of the genus Megalopyge in French Guiana with an
      atypical clinical presentation, based on three observations.

PMID- 26205659
TI  - Sensory nerves contribute to cutaneous vasodilator response to cathodal
      stimulation in healthy rats.
AB  - Cutaneous current-induced vasodilation (CIV) in response to galvanic current
      application is an integrative model of neurovascular interaction that relies on
      capsaicin-sensitive fiber activation. The upstream and downstream mechanisms
      related to the activation of the capsaicin-sensitive fibers involved in CIV are
      not elucidated. In particular, the activation of cutaneous transient receptor
      potential vanilloid type-1 (TRPV1) channels and/or acid-sensing ion channels
      (ASIC) (activators mechanisms) and the release of calcitonin gene-related peptide
      (CGRP) and substance P (SP) (effector mechanisms) have been tested. To assess
      cathodal CIV, we measured cutaneous blood flow using laser Doppler flowmetry for
      20min following cathodal current application (240s, 100MUA) on the skin of the
      thigh in anesthetized healthy rats for 20min. CIV was studied in rats treated
      with capsazepine and amiloride to inhibit TRPV1 and ASIC channels, respectively;
      CGRP8-37 and SR140333 to antagonize CGRP and neurokinin-1 (NK1) receptors,
      respectively; compared to their respective controls. Cathodal CIV was attenuated
      by capsazepine (12+/-2% vs 54+/-6%, P<0.001), amiloride (19+/-8% vs 61+/-6%,
      P<0.01), CGRP8-37 (15+/-6% vs 61+/-6%, P<0.001) and SR140333 (9+/-5% vs 54+/-6%,
      P<0.001) without changing local acidification. This is the first integrative
      study performed in healthy rats showing that cutaneous vasodilation in response
      to cathodal stimulation is initiated by activation of cutaneous TRPV1 and ASIC
      channels likely through local acidification. The involvement of CGRP and NK1
      receptors suggests that cathodal CIV is the result of CGRP and SP released
      through activated capsaicin-sensitive fibers. Therefore cathodal CIV could be a
      valuable method to assess sensory neurovascular function in the skin, which would
      be particularly relevant to evaluate the presence of small nerve fiber disorders
      and the effectiveness of treatments. 

PMID- 26205661
TI  - Enantioselective pharmacokinetics of doxazosin and pharmacokinetic interaction
      between the isomers in rats.
AB  - In this study, the stereoselective pharmacokinetics of doxazosin enantiomers and
      their pharmacokinetic interaction were studied in rats. Enantiomer concentrations
      in plasma were measured using chiral high-pressure liquid chromatography (HPLC)
      with fluorescence detection after oral or intravenous administration of (-)-(R)
      doxazosin 3.0 mg/kg, (+)-(S)-doxazosin 3.0 mg/kg, and rac-doxazosin 6.0 mg/kg.
      AUC values of (+)-(S)-doxazosin were always larger than those of (-)-(R)
      doxazosin, regardless of oral or intravenous administration. The maximum plasma
      concentration (Cmax ) value of (-)-(R)-doxazosin after oral administration was
      significantly higher when given alone (110.5 +/- 46.4 ng/mL) versus in racemate
      (53.2 +/- 19.7 ng/mL), whereas the Cmax value of (+)-(S)-doxazosin did not change
      significantly. The area under the curve (AUC) and Cmax values for (+)-(S)
      doxazosin after intravenous administration were significantly lower, and its Cl
      value significantly higher, when given alone versus in racemate. We speculate
      that (-)-(R)-doxazosin increases (+)-(S)-doxazosin exposure probably by
      inhibiting the elimination of (+)-(S)-doxazosin, and the enantiomers may be
      competitively absorbed from the gastrointestinal tract. In conclusion, doxazosin
      pharmacokinetics are substantially stereospecific and enantiomer-enantiomer
      interaction occurs after rac-administration.

PMID- 26205660
TI  - The gastrin and cholecystokinin receptors mediated signaling network: a scaffold
      for data analysis and new hypotheses on regulatory mechanisms.
AB  - BACKGROUND: The gastrointestinal peptide hormones cholecystokinin and gastrin
      exert their biological functions via cholecystokinin receptors CCK1R and CCK2R
      respectively. Gastrin, a central regulator of gastric acid secretion, is involved
      in growth and differentiation of gastric and colonic mucosa, and there is
      evidence that it is pro-carcinogenic. Cholecystokinin is implicated in digestion,
      appetite control and body weight regulation, and may play a role in several
      digestive disorders. RESULTS: We performed a detailed analysis of the literature
      reporting experimental evidence on signaling pathways triggered by CCK1R and
      CCK2R, in order to create a comprehensive map of gastrin and cholecystokinin
      mediated intracellular signaling cascades. The resulting signaling map captures
      413 reactions involving 530 molecular species, and incorporates the currently
      available knowledge into one integrated signaling network. The decomposition of
      the signaling map into sub-networks revealed 18 modules that represent higher
      level structures of the signaling map. These modules allow a more compact mapping
      of intracellular signaling reactions to known cell behavioral outcomes such as
      proliferation, migration and apoptosis. The integration of large-scale protein
      protein interaction data to this literature-based signaling map in combination
      with topological analyses allowed us to identify 70 proteins able to increase the
      compactness of the map. These proteins represent experimentally testable
      hypotheses for gaining new knowledge on gastrin- and cholecystokinin receptor
      signaling. The CCKR map is freely available both in a downloadable, machine
      readable SBML-compatible format and as a web resource through PAYAO (
      http://sblab.celldesigner.org:18080/Payao11/bin/). CONCLUSION: We have
      demonstrated how a literature-based CCKR signaling map together with its protein
      interaction extensions can be analyzed to generate new hypotheses on molecular
      mechanisms involved in gastrin- and cholecystokinin-mediated regulation of
      cellular processes.

PMID- 26205662
TI  - Tyr724 phosphorylation of ELMO1 by Src is involved in cell spreading and
      migration via Rac1 activation.
AB  - BACKGROUND: The complex of Dock180/ELMO1 that functions as a bipartite guanine
      nucleotide exchange factor for Rac is essential for diverse physiological and
      pathological processes of cells such as cell migration, phagocytosis, and
      invasion of cancer cells. Among the Src-family tyrosine kinases (SFKs), it has
      been reported that Hck directly phosphorylates ELMO1, regulating phagocytosis by
      promoting activation of Rac1; however, the involvement of other SFKs in ELMO1
      phosphorylation has remained unknown. Here, we identified novel tyrosine (Y)
      residues of ELMO1 phosphorylated by SFKs, and examined the effects on Rac1
      activity, cell adhesion, spreading, and cell motility on extracellular matrix
      (ECM). RESULTS: In this study, we unveiled that Src and Fyn can induce tyrosine
      phosphorylation of ELMO1 in in vivo and in vitro phosphorylation assays.
      Mutational analyses identified both Y720 and Y724 residues of ELMO1 as Src
      mediated phosphorylation sites, preferentially on Y724. Single substitution of
      Y724 to Phe abrogated Rac1 activation triggered by Src. To elucidate the
      biological function of pY724, we established NIH3T3 cells stably expressing wild
      type ELMO1 or its Y724F mutant together with Dock180. Among them, Y724-deficient
      cells exhibited a depletion of Rac1 activity with diminished phosphorylation of
      ELMO1 even upon the ECM-stimulation. It is noteworthy that NIH3T3 cells with
      ELMO1 Y724F were strikingly defective to promote cell spreading on fibronectin
      coated dish, concomitantly exhibiting immature assemblies of actin stress fibers
      and focal adhesions. Eventually, ELMO1 Y724F significantly impaired cell
      migration. CONCLUSION: These results define that Src-mediated Y724
      phosphorylation in ELMO1 plays a critical role for cell spreading via activation
      of Rac1, leading to promotion of cell migration. As the overexpression and/or
      hyperactivation of Src have been shown in a wide variety of human cancers, Src
      mediated phosphorylation of Y724 in ELMO1 may regulate cancer cell adhesion to
      the ECM, invasion into surrounding tissues, and subsequent distant metastasis.

PMID- 26205663
TI  - Systematic analysis of the relationship between antibiotic use and extended
      spectrum beta-lactamase resistance in Enterobacteriaceae in a French hospital: a
      time series analysis.
AB  - The influence of hospital use of antibiotics other than cephalosporins and
      fluoroquinolones on extended-spectrum beta-lactamase (ESBL) resistance among
      Enterobacteriaceae is poorly known. Our objective was to explore the association
      between ESBL and hospital use of various classes of antibacterial agents. The
      relationship between monthly use of 19 classes of antibacterial agents and
      incidence of nosocomial ESBL-producing Enterobacteriaceae in a French hospital
      was studied between 2007 and 2013. Five antibiotic classes were significantly and
      independently associated with ESBL resistance. Uses of tetracyclines (link
      estimate +/- SE, 0.0066 +/- 0.0033), lincosamides (0.0093 +/- 0.0029), and other
      antibacterial agents (0.0050 +/- 0.0023) were associated with an increased
      incidence, while nitrofurantoin (-0.0188 +/- 0.0062) and ticarcillin and
      piperacillin with or without enzyme inhibitor (-0.0078 +/- 0.0031) were
      associated with a decreased incidence. In a multivariate model including 3rd- and
      4th-generation cephalosporins, fluoroquinolones, amoxicillin, and amoxicillin
      clavulanate, 3rd- and 4th-generation cephalosporins (0.0019 +/- 0.0009) and
      fluoroquinolones (0.0020 +/- 0.0008) were associated with an increased ESBL
      resistance, whereas amoxicillin and amoxicillin-clavulanate were not. Hospital
      use of tetracyclines and lincosamides may promote ESBL resistance in
      Enterobacteriaceae. Nitrofurantoin and ticarcillin and piperacillin with or
      without enzyme inhibitor should be considered as potential alternatives to broad
      spectrum cephalosporins and fluoroquinolones to control the diffusion of ESBL
      resistance.

PMID- 26205664
TI  - Factors predicting kidney damage in Puumala virus infected patients in Southern
      Denmark.
AB  - In Europe, infections with Puumala hantavirus cause nephropathia epidemica.
      Presently the risk factors predicting severe kidney damage after Puumala virus
      infection are not well known. The objective of the study was to investigate
      environmental and individual factors predicting severe kidney damage caused by
      serologically established Puumala infections. In a nationwide cohort study we
      investigated all serologically established Puumala infections in Southern Denmark
      from 1996 to 2012. A total of 184 patients had serologically verified Puumala
      virus infection. In patients with Puumala virus infections the decrease of
      platelet counts preceded acute kidney failure. Multivariable logistic regression
      demonstrated that recent activities in the forest, platelet counts, and flu-like
      symptoms predicted estimated glomerular filtration rates less than 30 mL/min/1.73
      m(2), but not age, gender, fever, nor abdominal pain. Severe kidney damage in
      Puumala infections in Southern Denmark is associated with the risk of recent
      activities in the forest.

PMID- 26205665
TI  - Risk factors for and impact of carbapenem-resistant Acinetobacter baumannii
      colonization and infection: matched case-control study.
AB  - The objective of this investigation was to identify risk factors for carbapenem
      resistant Acinetobacter baumannii (CRAB) and its association with mortality. A
      population-based matched case-control study using the computerized database of
      Clalit Health Services (CHS) in the period between 2007 and 2012 was conducted.
      Hospitalized patients with CRAB colonization or infection were compared to
      hospitalized patients without evidence of A. baumannii, matched by age, ward of
      hospitalization, season, Charlson score, and length of hospitalization. Risk
      factors for CRAB isolation were searched for using multivariate analysis.
      Association of CRAB and other risk factors with mortality were assessed in the
      cohort. A total of 1190 patients with CRAB were matched to 1190 patients without
      CRAB. Low socioeconomic status was independently associated with CRAB isolation
      and CRAB bacteremia [odds ratio 2.18, 95% confidence interval (CI) 1.02-5]. Other
      risk factors were invasive procedures and bacteremia with other pathogens prior
      to CRAB isolation, and various comorbidities. Among all patients, CRAB isolation
      was independently associated with increased mortality (hazard ratio 2.33, 95% CI
      2.08-2.6). Socioeconomic status is associated with health outcomes. Our
      population-based study revealed an almost doubled risk for CRAB in patients at
      lower socioeconomic status and an association with healthcare exposure. CRAB was
      associated with mortality and might become a risk indicator for complex morbidity
      and mortality.

PMID- 26205666
TI  - Colonization, safety, and tolerability study of the Streptococcus salivarius
      24SMBc nasal spray for its application in upper respiratory tract infections.
AB  - Streptococcus salivarius, a non-pathogenic species and the predominant colonizer
      of the oral microbiota, finds a wide application in the prevention of upper
      respiratory tract infections, also reducing the frequency of their main
      pathogens. In this pilot study, the primary objective was to evaluate the safety
      and tolerability of a nasal spray, S. salivarius 24SMBc, as a medical device in a
      clinical study involving 20 healthy adult subjects. The secondary aim was to
      determine the ability of colonization assessed by molecular fingerprinting.
      Twenty healthy adult subjects, aged between 30 and 54 years, without a medical
      history of recurrent otitis media, were enrolled. All patient characteristics
      fulfilled the inclusion criteria. All subjects were treated daily for 3 days with
      the nasal spray containing S. salivarius 24SMBc at a concentration of 5 * 10(9)
      colony-forming units (CFU)/ml. The persistence of S. salivarius in the
      nasopharynx was investigated by the antagonism test and random amplified
      polymorphic DNA polymerase chain reaction (RAPD-PCR). The tolerability and safety
      were clinically assessed by clinical examinations during treatment. Our results
      demonstrate the capability of S. salivarius 24SMBc to colonize the rhinopharynx
      tissues in 95% of subjects and persist in 55% of them after 6 days from the last
      dose of the formulation, maintaining a concentration of 10(5) CFU/ml. The
      treatment was well tolerated by all healthy patients and no adverse effects were
      found. The topical application of streptococcal probiotics is a relatively
      undeveloped field but is becoming an attractive approach for both prevention and
      therapy, especially for pediatric age patients. S. salivarius 24SMBc possess
      characteristics making this strain suitable for use in bacteriotherapy.

PMID- 26205667
TI  - Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent
      DNA repair process.
AB  - DNA double-strand breaks (DSBs) are often targeted to nuclear pore complexes
      (NPCs) for repair. How targeting is achieved and the DNA repair pathways involved
      in this process remain unclear. Here, we show that the kinesin-14 motor protein
      complex (Cik1-Kar3) cooperates with chromatin remodellers to mediate interactions
      between subtelomeric DSBs and the Nup84 nuclear pore complex to ensure cell
      survival via break-induced replication (BIR), an error-prone DNA repair process.
      Insertion of a DNA zip code near the subtelomeric DSB site artificially targets
      it to NPCs hyperactivating this repair mechanism. Kinesin-14 and Nup84 mediate
      BIR-dependent repair at non-telomeric DSBs whereas perinuclear telomere tethers
      are only required for telomeric BIR. Furthermore, kinesin-14 plays a critical
      role in telomerase-independent telomere maintenance. Thus, we uncover roles for
      kinesin and NPCs in DNA repair by BIR and reveal that perinuclear telomere
      anchors license subtelomeric DSBs for this error-prone DNA repair mechanism. 

PMID- 26205668
TI  - Quality of transition to end-of-life care for cancer patients in the intensive
      care unit.
AB  - BACKGROUND: There have been few studies that have evaluated the quality of end-of
      life care (EOLC) for cancer patients in the ICU. The aim of this study was to
      explore the quality of transition to EOLC for cancer patients in ICU. METHODS:
      The study was undertaken on medical patients admitted to a specialist cancer
      hospital ICU over 6 months. Quantitative and qualitative methods were used to
      explore quality of transition to EOLC using documentary evidence. Clinical
      parameters on ICU admission were reviewed to determine if they could be used to
      identify patients who were likely to transition to EOLC during their ICU stay.
      RESULTS: Of 85 patients, 44.7% transitioned to EOLC during their ICU stay.
      Qualitative and quantitative analysis of the patients' records demonstrated that
      there was collaborative decision-making between teams, patients and families
      during transition to EOLC. However, 51.4 and 40.5% of patients were too unwell to
      discuss transition to EOLC and DNACPR respectively. In the EOLC cohort, 76.3%
      died in ICU, but preferred place of death known in only 10%. Age, APACHE II
      score, and organ support, but not cancer diagnosis, were identified as associated
      with transition to EOLC (p = 0.017, p < 0.0001 and p = 0.001). CONCLUSIONS:
      Advanced EOLC planning in patients with progressive disease prior to acute
      deterioration is warranted to enable patients' wishes to be fulfilled and ceiling
      of treatments agreed. Better documentation and development of validated tools to
      measure the quality EOLC transition on the ICU are needed.

PMID- 26205669
TI  - [Practical update of Tsaktubo syndrome].
AB  - Takotsubo syndrome, apical ballooning or "broken heart" syndrome, is a growing
      diagnostic entity which clinically mimics an acute coronary syndrome. Included
      into the stress cardiomyopathy group of cardiopathies, this condition is
      characterized by the absence of potentially responsible coronary lesions, while
      displaying a transient abnormal ventricular motion, usually affecting various
      coronary territories. It is generally observed in postmenopausal women and
      frequently seen in the presence of a stressful situation, both physical and
      emotional. With a prevalence of 1.2% among patients undergoing a cardiac
      catheterization with a suspected diagnosis of acute coronary syndromes, Takotsubo
      syndrome usually has a good prognosis. However, complications can occur in the
      acute phase, generally heart failure, which can even lead to death. In this
      review we discuss the latest available information on this disease and present it
      in a practical and useful way for the attending physician. 

PMID- 26205671
TI  - Multiform Korean handwriting authentication by forensic document examiners.
AB  - Forensic document examiners of Multiform Korean handwriting were tested using
      blind trials. A small number of experts (4) were tested for their performance and
      the test involved three steps. The participants each conducted a one-person
      examination first, then paired up with another person to perform the two-person
      examination and then finally the four people came together to conduct a group
      examination. When the experts actively exchanged opinions, the percentage of
      misleading decisions decreased while the percentage of inconclusive opinions
      increased. The deviations in the percentages of misleading results for different
      handwriting samples (long, short, signature) were not significant, while the
      disguised handwriting results showed the highest percentage of misleading
      conclusions. A special attention to artificially modified handwriting is
      therefore warranted rather than focusing on the number of letters. 

PMID- 26205670
TI  - Severely deranged vital signs as triggers for acute treatment modifications on an
      intensive care unit in a low-income country.
AB  - BACKGROUND: Critical care saves lives of the young with reversible disease.
      Little is known about critical care services in low-income countries. In a
      setting with a shortage of doctors the actions of the nurse bedside are likely to
      have a major impact on the outcome of critically ill patients with rapidly
      changing physiology. Identification of severely deranged vital signs and
      subsequent treatment modifications are the basis of modern routines in critical
      care, for example goal directed therapy and rapid response teams. This study
      assesses how often severely deranged vital signs trigger an acute treatment
      modification on an Intensive Care Unit (ICU) in Tanzania. METHODS: A medical
      records based, observational study. Vital signs (conscious level, respiratory
      rate, oxygen saturation, heart rate and systolic blood pressure) were collected
      as repeated point prevalences three times per day in a 1-month period for all
      adult patients on the ICU. Severely deranged vital signs were identified and
      treatment modifications within 1 h were noted. RESULTS: Of 615 vital signs
      studied, 126 (18%) were severely deranged. An acute treatment modification was in
      total indicated in 53 situations and was carried out three times (6%) (2/32 for
      hypotension, 0/8 for tachypnoea, 1/6 for tachycardia, 0/4 for unconsciousness and
      0/3 for hypoxia). CONCLUSIONS: This study suggests that severely deranged vital
      signs are common and infrequently lead to acute treatment modifications on an ICU
      in a low-income country. There may be potential to improve outcome if nurses are
      guided to administer acute treatment modifications by using a vital sign directed
      approach. A prospective study of a vital sign directed therapy protocol is
      underway.

PMID- 26205672
TI  - Prosthetists' and Orthotists' experience of their work and workspace -
      characterising the physical and organisational environment: Focus group findings.
AB  - BACKGROUND: Little research has been undertaken into occupational health and
      safety in the Prosthetics and Orthotics profession. OBJECTIVES: To identify
      physical, psychosocial and environmental workplace experiences of Prosthetists
      and Orthotists in organisational settings. STUDY DESIGN: Qualitative methodology,
      cross-sectional design, using thematically analysed data collected from focus
      groups. METHODS: Focus groups explored workplace and work experiences across
      varied Prosthetic and Orthotic settings. Data were thematically analysed to
      identify physical, psychosocial and environmental workplace experiences. RESULTS:
      Three major themes, Demands of Work Practice, Impacts on the Individual and Job
      Design, were identified as problematic. A latent theme Perceptions of Others of
      P&O highlighted a lack of understanding of the Prosthetics and Orthotics job role
      outside the profession. CONCLUSION: This first study of occupational health and
      safety in the Prosthetics and Orthotics profession identifies a number of
      important physical and psychosocial issues, including characteristics that have
      been previously identified as risk factors for work-related musculoskeletal
      disorders. Findings from the study indicate that some Australian organisations
      lack understanding of the Prosthetics and Orthotics job role, which results in
      inappropriate expectations of Prosthetics and Orthotics professionals. Preventing
      injuries and retaining experienced Prosthetists and Orthotists in the workplace
      is vital for the profession, and as a result, issues raised in this study require
      further exploration and then development of appropriate management strategies.
      CLINICAL RELEVANCE: This is the first study characterising the experiences of
      work and risk of injuries in Prosthetists and Orthotists. Preventing injuries and
      retaining experienced Prosthetists and Orthotists in the workplace is vital for
      the international profession. Issues raised in this study require further
      exploration and then development of appropriate management strategies.

PMID- 26205673
TI  - Bagherzadeh Cham et al. Prosth Orthot Int 2014; 38: 310-315.

PMID- 26205675
TI  - Non-medical prescription opioid use among youth: Gaining perspective from decades
      of previous drug use epidemics.

PMID- 26205674
TI  - Treatment of chronic hepatitis B with pattern recognition receptor agonists:
      Current status and potential for a cure.
AB  - Hepatitis B virus (HBV) has been considered to be a "stealth virus" that induces
      negligible innate immune responses during the early phase of infection. However,
      recent studies with newly developed experimental systems have revealed that virus
      infection can be recognized by pattern recognition receptors (PRR), eliciting a
      cytokine response that controls the replication of the virus. The molecular
      mechanisms by which interferons and other inflammatory cytokines suppress HBV
      replication and modulate HBV cccDNA metabolism and function are just beginning to
      be revealed. In agreement with the notion that the developmental and functional
      status of intrahepatic innate immunity determines the activation and maturation
      of the HBV-specific adaptive immune response and thus the outcome of HBV
      infection, pharmacological activation of intrahepatic innate immune responses
      with TLR7/8/9 or STING agonists efficiently controls HBV infection in preclinical
      studies and thus holds great promise for the cure of chronic hepatitis B. This
      article forms part of a symposium in Antiviral Research on "An unfinished story:
      from the discovery of the Australia antigen to the development of new curative
      therapies for hepatitis B." 

PMID- 26205676
TI  - Drug quality assessment practices and communication of drug alerts among people
      who use drugs.
AB  - BACKGROUND: Regional health bodies in British Columbia (BC) issue drug alerts to
      the public when health risks associated with drug quality are identified, such as
      increased illicit drug deaths, overdoses or other harms. There is a lack of
      evidence-based guidelines for producing timely, effective public health alerts to
      mitigate these harms. This study sought to understand (1) the practices used by
      people who use drugs (PWUD) to assess the quality of street drugs and reduce
      harms from adulterants and (2) how drug alerts could be better communicated to
      PWUD. METHODS: Guided by interpretive and descriptive methodology, this study
      consisted of brief questionnaires and in-depth focus groups with 32 PWUD.
      RESULTS: Findings suggest the most effective and trusted information about drug
      quality was primarily from: (a) trusted, reputable dealers or (b) peer-based
      social networks. Most PWUD thought information received through health service
      providers was not timely and did not discuss drug quality with them. A number of
      concrete guidelines were suggested by participants to improve the effectiveness
      of drug alert modes and methods of communication in the community, including the
      use of language on drug alert postings that implies harm, indicates what drug
      effects to look for, and suggests appropriate responses to overdose, such as the
      use of naloxone. Participants also emphasized the need to date posters and remove
      them in a timely manner so as to not desensitize the community to such alerts.
      CONCLUSION: Since it is difficult to control adulteration practices in an
      unregulated drug market, this study suggests methods of effectively producing and
      communicating drug alerts among PWUD to mitigate harms associated with drug use.

PMID- 26205677
TI  - At the edge of chaos--error tolerance and the maintenance of Levy statistics in
      animal movement: Comment on "Liberating Levy walk research from the shackles of
      optimal foraging" by A.M. Reynolds.

PMID- 26205678
TI  - 2,2'-Disilylazobenzenes featuring double intramolecular nitrogen???silicon
      coordination: a photoisomerizable fluorophore.
AB  - (E)-4,4'-Dimethyl-2,2'-disilylazobenzenes were synthesized. Double intramolecular
      N???Si coordination in the bis(fluorodimethylsilyl) and bis(trifluorosilyl)
      derivatives was confirmed using X-ray crystallographic analysis and (29)Si NMR
      spectroscopy. In the absorption bands, due to the pi,pi* transitions,
      introduction of silyl groups was found to cause a bathochromic shift. In contrast
      to most azobenzenes, which do not fluoresce at all, the (E)-2,2'
      bis(trifluorosilyl)azobenzene derivative with the N???Si coordination fluoresced
      a yellow-green colour at room temperature. Methyl and trifluorosilyl groups
      lowered the n and pi* orbitals, as revealed by DFT calculations. As a result, the
      lowest singlet excitation energy state is found to be the allowed pi,pi*
      transition, different from the forbidden n,pi* transition in general azobenzenes,
      as revealed by TD-DFT calculations. The allowed transition character of the
      lowest singlet excited state and moderately rigid conformation of the azo moiety,
      provided by the double N???Si coordination, account for the fluorescence
      emission. Nevertheless, the N???Si coordination is weak enough to be cleaved upon
      photoexcitation, and thus the (E)-2,2'-disilylazobenzenes undergo
      photoisomerization to the (Z)-isomers. Both the photoisomerization and
      fluorescence emission properties of the azobenzene moiety have been achieved for
      the first time. After photoisomerization of the (E)-2,2'-disilylazobenzenes to
      the corresponding (Z)-isomer, they do not fluoresce. This change in the
      fluorescence intensity upon photoisomerization is useful for the regulation of
      fluorescence properties. Therefore, this compound can be recognized as a unique
      photoisomerizable fluorophore to regulate the fluorescence intensity using a
      single light source.

PMID- 26205679
TI  - Dietary guidelines to nourish humanity and the planet in the twenty-first
      century. A blueprint from Brazil.
AB  - OBJECTIVE: To present and discuss the dietary guidelines issued by the Brazilian
      government in 2014. DESIGN: The present paper describes the aims of the
      guidelines, their shaping principles and the approach used in the development of
      recommendations. The main recommendations are outlined, their significance for
      the cultural, socio-economic and environmental aspects of sustainability is
      discussed, and their application to other countries is considered. SETTING:
      Brazil in the twenty-first century. SUBJECTS: All people in Brazil, now and in
      future. RESULTS: The food- and meal-based Brazilian Dietary Guidelines address
      dietary patterns as a whole and so are different from nutrient-based guidelines,
      even those with some recommendations on specific foods or food groups. The
      guidelines are based on explicit principles. They take mental and emotional well
      being into account, as well as physical health and disease prevention. They
      identify diet as having cultural, socio-economic and environmental as well as
      biological and behavioural dimensions. They emphasize the benefits of dietary
      patterns based on a variety of natural or minimally processed foods, mostly
      plants, and freshly prepared meals eaten in company, for health, well-being and
      all relevant aspects of sustainability, as well as the multiple negative effects
      of ready-to-consume ultra-processed food and drink products. CONCLUSIONS: The
      guidelines' recommendations are designed to be sustainable personally,
      culturally, socially, economically and environmentally, and thus fit to face this
      century. They are for foods, meals and dietary patterns of types that are already
      established in Brazil, which can be adapted to suit the climate, terrain and
      customs of all countries.

PMID- 26205680
TI  - Applicability, Commercial Utility and Recent Patents on Starch and Starch
      Derivative as Pharmaceutical Drug Delivery Carrier.
AB  - Natural polymers are widely utilized in pharmaceutical and food industries.
      Starch, a major carbohydrate is a staple food in human and animal diets which is
      simply extractable from various sources, like potato, maize, corn, wheat, etc. It
      is widely used as a raw material in various food and non food industries as well
      as in paper, textile and other industries. This article summarizes the starch and
      modification of starch and to produce a novel molecule with various applications
      in industries including number of advances in pharmaceutical industry. The unique
      characteristics of starch and their modified form can be successfully used as
      drug delivery carriers in various pharmaceutical preparations. It is widely used
      as controlled and sustained release polymer, tablet disintegrant, drug delivery
      carrier, plasma volume expander and also finds its applicability in bone tissue
      engineering and in artificial red cells. It also includes the patents related to
      starch and modified starch based products and their commercial utility. 

PMID- 26205681
TI  - In Situ Gelling Ophthalmic Drug Delivery System: An Overview and Its
      Applications.
AB  - Ophthalmic drug delivery system is very interesting and challenging due to the
      normal physiologically factor of eyes which reduces the bioavailability of ocular
      products. The development of new ophthalmic dosage forms for existing drugs to
      improve efficacy and bioavailability, patient compliance and convenience has
      become one of the main trend in the pharmaceuticals industry. The present review
      encompasses various conventional and novel ocular drug delivery systems, methods
      of preparation, characterization and recent research in this area. Furthermore,
      the information on various commercially available in situ gel preparations and
      the existing patents of in situ drug delivery systems i.e. in situ gel formation
      of pectin, in situ gel for therapeutic use, medical uses of in situ formed gels
      and in situ gelling systems as sustained delivery for front of eye are also
      covered in this review. 

PMID- 26205682
TI  - [Depression, anxiety and stress scales: DASS--A screening procedure not only for
      pain patients].
AB  - BACKGROUND: The assessment of mental distress is a central aspect in pain
      research and treatment. Particularly for depression the comorbidity with pain
      poses methodological and conceptual challenges. This study examined the
      psychometric properties of the short version of the depression, anxiety and
      stress scale (DASS), used in both pain research and treatment and constructed to
      overcome the particular problems by omitting somatic items and concentrating on
      the psychological core aspects of depression, anxiety and stress. METHOD: The
      psychometric properties of the DASS-21 were compared between patients with pain
      and various people without any pain problems (N = 950). The DASS has three
      subscales, depression, anxiety and stress, each with seven items. The construct
      validity of the DASS was examined using the hospital anxiety and depression scale
      (HADS) for anxiety and depression and the general depression scale (Allgemeine
      Depressionsskala, ADS) for depression. The sensitivity and specificity for
      depression were determined against a structured interview for diagnostic and
      statistical manual of mental disorders (DSM-IV) and compared with the Center for
      Epidemiological Studies depression scale (CESD) and HADS in pain patients.
      RESULTS: Cronbach's alpha of the DASS for the depression subscale was at least
      0.91, while the anxiety and stress subscales had Cronbach alphas of 0.78-0.82 and
      0.81-0.89, respectively. Although the depression subscale has only 7 items, it is
      just as reliable as the ADS with 21 items. It also has a better sensitivity and
      specificity than the HADS in identifying clinical patients with depression.
      DISCUSSION: The DASS is a reliable questionnaire, free to use and brief to
      administer; therefore, it is an alternative to the previously used instruments
      for the screening of depression. Furthermore, the subscale stress measures
      irritability and tension, which are important aspects of pain experience but
      underused in assessment procedures for the diagnosis and treatment evaluation of
      patients with pain.

PMID- 26205683
TI  - The Effectiveness of Challenging Skills in Work With Young Offenders.
AB  - Probation officers and others who work with young offenders often challenge or
      confront their clients in relation to pro-criminal comments and criminal
      behaviour. There is, however, very little research that can inform practitioners
      about which forms of challenging most effectively engage young people. This study
      examines the use of challenging by youth justice workers in New South Wales,
      Australia. Researchers observed and audiotaped 116 interviews between youth
      justice workers and their clients with a view to examining the nature of
      challenging used by workers and the response of young people to different forms
      of challenging. Qualitative and quantitative findings indicate that the clients
      were more positively engaged by, and responsive to, challenging that was
      exploratory, non-blaming, and accompanied by positive reinforcement of their
      strengths. Excerpts taken from the interviews provide examples of high- and low
      level use of the skill of challenging.

PMID- 26205684
TI  - Posthospitalization Outcomes for Psychiatric Sex Offenders: Comparing Two
      Treatment Protocols.
AB  - This study evaluates the effectiveness of safe offender strategies (SOS) in
      comparison with relapse prevention (RP) in a sample of 91 inpatient males in a
      secure psychiatric setting. All men evidenced a history of violent sexual
      offending and were diagnosed with serious psychiatric disorders and/or
      intellectual disabilities. Participants who received SOS (n= 58) and RP (n= 33)
      were followed from 6 to 36 months post release. SOS clients were significantly
      less likely to be arrested (0%) or rehospitalized (5.2%) than RP clients (9%
      arrested; 54.5% rehospitalized). In addition, SOS clients were more likely to
      transition continuously to less restrictive alternatives, with no returns to high
      security, in comparison with RP clients. The authors discuss implications for use
      of SOS, a treatment that facilitates skills development and affects global self
      regulatory functioning, particularly in sex offenders with serious mental illness
      or intellectual impairment, in promoting community reintegration and limiting
      returns to psychiatric settings. 

PMID- 26205685
TI  - Desvenlafaxine for the acute treatment of depression: a systematic review and
      meta-analysis.
AB  - INTRODUCTION: Desvenlafaxine, the active metabolite of venlafaxine, was approved
      in 2008 by the FDA for the treatment of depression. The aim of the present review
      is to provide an overview of the existing trials with desvenlafaxine and assess
      its overall efficacy and tolerability. METHODS: We searched in PubMed, EMBASE and
      the Cochrane Library for eligible studies (double-blind randomized control
      trials). A random effects model was used for the estimation of effect sizes.
      RESULTS: 17 trials were found in total. In the placebo-controlled trials the
      overall risk ratio for response was 1.24 (1.16-1.32, p<0.001), for remission 1.29
      (1.16-1.43, p<0.001), for dropouts 1.16 (0.99-1.35, p=0.066) and for dropouts due
      to adverse events 1.98 (1.45-2.69, p<0.001). There were no differences between
      the various doses that were used (i. e., 50 mg, 100 mg, 200 mg, 400 mg). The mean
      risk ratio for response in the head-to-head trials was 0.90 (0.82-0.98, p=0.014)
      and for remission 0.82 (0.71-0.95, p=0.009). DISCUSSION: The risk ratios for
      response and remission were moderate. We further provide some evidence that
      desvenlafaxine might not be as efficacious as other antidepressants.

PMID- 26205687
TI  - Characterisation of the relationship between Spirometra erinaceieuropaei and
      Diphyllobothrium species using complete cytb and cox1 genes.
AB  - Spirometra erinaceieuropaei is an important diphyllobothriid cestode whose larval
      plerocercoid (sparganum) can parasitise humans, causing sparganosis. In China,
      sparganosis is an important foodborne parasitic zoonosis and poses a serious
      threat to human health. However, our knowledge of the taxonomic classification of
      S. erinaceieuropaei and its relationship with other diphyllobothriid cestodes,
      such as Diphyllobothrium, remains fragmentary. In this study, we determined the
      complete sequences of cytochrome b (cytb) and cytochrome c oxidase subunit I
      (cox1) genes from 61 isolates of S. erinaceieuropaei collected from 11
      geographical locations in eastern China and compared them to the sequences of
      Diphyllobothrium species from the GenBank database. Then, we evaluated the
      genetic variation of S. erinaceieuropaei and the phylogenetic relationship
      between S. erinaceieuropaei and Diphyllobothrium. Both negative Tajima's D and
      Fu's FS values of neutrality tests and unimodal curve of mismatch distribution
      analyses supported demographic population expansion. Bayesian skyline plot (BSP)
      analyses indicated that a population expansion occurred in the Pleistocene.
      Phylogenetic analysis based on cytb, cox1, and cytb+cox1 under all three methods
      tested (neighbour-joining, maximum parsimony, and maximum likelihood) suggested
      that the S. erinaceieuropaei isolates from eastern China and the genus
      Diphyllobothrium are separate monophyletic groups. Furthermore, the uncorrelated
      log-normal relaxed molecular-clock model suggested that divergence between
      Spirometra and Diphyllobothrium began in the late Miocene. 

PMID- 26205686
TI  - Transcutaneous electrical spinal-cord stimulation in humans.
AB  - Locomotor behavior is controlled by specific neural circuits called central
      pattern generators primarily located at the lumbosacral spinal cord. These
      locomotor-related neuronal circuits have a high level of automaticity; that is,
      they can produce a "stepping" movement pattern also seen on electromyography
      (EMG) in the absence of supraspinal and/or peripheral afferent inputs. These
      circuits can be modulated by epidural spinal-cord stimulation and/or
      pharmacological intervention. Such interventions have been used to neuromodulate
      the neuronal circuits in patients with motor-complete spinal-cord injury (SCI) to
      facilitate postural and locomotor adjustments and to regain voluntary motor
      control. Here, we describe a novel non-invasive stimulation strategy of painless
      transcutaneous electrical enabling motor control (pcEmc) to neuromodulate the
      physiological state of the spinal cord. The technique can facilitate a stepping
      performance in non-injured subjects with legs placed in a gravity-neutral
      position. The stepping movements were induced more effectively with multi-site
      than single-site spinal-cord stimulation. From these results, a multielectrode
      surface array technology was developed. Our preliminary data indicate that use of
      the multielectrode surface array can fine-tune the control of the locomotor
      behavior. As well, the pcEmc strategy combined with exoskeleton technology is
      effective for improving motor function in paralyzed patients with SCI. The
      potential impact of using pcEmc to neuromodulate the spinal circuitry has
      significant implications for furthering our understanding of the mechanisms
      controlling locomotion and for rehabilitating sensorimotor function even after
      severe SCI. 

PMID- 26205688
TI  - Evolutionary characterization of Tembusu virus infection through identification
      of codon usage patterns.
AB  - Tembusu virus (TMUV) is a single-stranded, positive-sense RNA virus. As reported,
      TMUV infection has resulted in significant poultry losses, and the virus may also
      pose a threat to public health. To characterize TMUV evolutionarily and to
      understand the factors accounting for codon usage properties, we performed, for
      the first time, a comprehensive analysis of codon usage bias for the genomes of
      60 TMUV strains. The most recently published TMUV strains were found to be widely
      distributed in coastal cities of southeastern China. Codon preference among TMUV
      genomes exhibits a low bias (effective number of codons (ENC)=53.287) and is
      maintained at a stable level. ENC-GC3 plots and the high correlation between
      composition constraints and principal component factor analysis of codon usage
      demonstrated that mutation pressure dominates over natural selection pressure in
      shaping the TMUV coding sequence composition. The high correlation between the
      major components of the codon usage pattern and hydrophobicity (Gravy) or
      aromaticity (Aromo) was obvious, indicating that properties of viral proteins
      also account for the observed variation in TMUV codon usage. Principal component
      analysis (PCA) showed that CQW1 isolated from Chongqing may have evolved from
      GX2013H or GX2013G isolated from Guangxi, thus indicating that TMUV likely
      disseminated from southeastern China to the mainland. Moreover, the preferred
      codons encoding eight amino acids were consistent with the optimal codons for
      human cells, indicating that TMUV may pose a threat to public health due to
      possible cross-species transmission (birds to birds or birds to humans). The
      results of this study not only have theoretical value for uncovering the
      characteristics of synonymous codon usage patterns in TMUV genomes but also have
      significant meaning with regard to the molecular evolutionary tendencies of TMUV.

PMID- 26205689
TI  - Analysis of the intactness of Helicobacter pylori cag pathogenicity island in
      Iranian strains by a new PCR-based strategy and its relationship with virulence
      genotypes and EPIYA motifs.
AB  - Variants of the Helicobacter pylori cag pathogenicity island (cagPAI) and certain
      virulence genotypes have been proposed to be associated with different gastric
      disorders. In the present study, we designed a new PCR-based strategy to
      investigate the intactness of cagPAI in Iranian patients using highly specific
      primer sets spanning the cagPAI region. The possible relationship between the
      cagPAI status of the strains and clinical outcomes was also determined. We also
      characterized virulence genotypes (cagL, cagA, vacA, babA2 and sabA) and variants
      of CagA EPIYA motifs in these strains. H. pylori was detected in 61 out of 126
      patients with various gastroduodenal diseases. The cagL, cagA, vacA s1m1, vacA
      s1m2, vacA s2m2, babA2, and sabA genotypes were detected in 96.7%, 85.2%, 29.5%,
      45.9%, 24.6%, 96.7%, and 83.6% of the strains, respectively. Among the 52 cagA
      positive strains, EPIYA motifs ABC, ABCC, ABCCC, and mixed types were orderly
      detected in the 39, 7, 1, and 5 strains. The cagPAI positivity included both
      intact and partially deleted, with the overall frequencies of 70.5% and 26.2%,
      respectively. The majority of the strains from patients with PUD (87.5%), gastric
      erosion (83.3%) and cancer (80%) presented an intact cagPAI, while a lower
      frequency of cagPAI intactness was detected in gastritis patients (61.1%).
      However, no significant relationship was found between the possession of intact
      cagPAI and clinical outcomes. Furthermore, we found that cagA and vacA s1m1
      genotypes were significantly correlated with intact cagPAI (P=0.015 and P=0.012).
      A significant correlation was also found between EPIYA-ABC and intact cagPAI
      (P=0.010). The proposed PCR-based scheme was found to be useful for determining
      the intactness of cagPAI. Our findings also indicate that the cagPAI appears to
      be intact and rather conserved in majority of Iranian strains. Finally, our study
      proposed that H. pylori strains with partially deleted cagPAI were less likely to
      cause severe diseases in comparison with those carrying intact cagPAI. 

PMID- 26205690
TI  - Mitochondrial DNA sequences of 37 collar-spined echinostomes (Digenea:
      Echinostomatidae) in Thailand and Lao PDR reveals presence of two species:
      Echinostoma revolutum and E. miyagawai.
AB  - The "37 collar-spined" or "revolutum" group of echinostomes is recognized as a
      species complex. The identification of members of this complex by morphological
      taxonomic characters is difficult and confusing, and hence, molecular analyses
      are a useful alternative method for molecular systematic studies. The current
      study examined the genetic diversity of those 37 collar-spined echinostomes which
      are recognized morphologically as Echinostoma revolutum in Thailand and Lao PDR
      using the cytochrome c oxidase subunit 1 (CO1) and the NADH dehydrogenase subunit
      1 (ND1) sequences. On the basis of molecular investigations, at least two species
      of 37 collar-spined echinostomes exist in Southeast Asia, namely E. revolutum and
      Echinostoma miyagawai. The specimens examined in this study, coming from ducks in
      Thailand and Lao PDR, were compared to isolates from America, Europe and
      Australia for which DNA sequences are available in public databases. Haplotype
      analysis detected 6 and 26 haplotypes when comparing the CO1 sequences of E.
      revolutum and E. miyagawai, respectively, from different geographical isolates
      from Thailand and Lao PDR. The phylogenetic trees, ND1 haplotype network and
      genetic differentiation (phiST) analyses showed that E. revolutum were
      genetically different on a continental scale, i.e. Eurasian and American
      lineages. 

PMID- 26205691
TI  - Identification of a multi-reassortant G12P[9] rotavirus with novel VP1, VP2, VP3
      and NSP2 genotypes in a child with acute gastroenteritis.
AB  - The G12 rotavirus genotype is globally emerging to cause severe gastroenteritis
      in children. Common G12 rotaviruses have either a Wa-like or DS-1-like genome
      constellation, while some G12 strains may have unusual genome composition. In
      this study, we determined the full-genome sequence of a G12P[9] strain (ME848/12)
      detected in a child hospitalized with acute gastroenteritis in Italy in 2012.
      Strain ME848/12 showed a complex genetic constellation (G12-P[9]-I17-R12-C12-M11
      A12-N12-T7-E6-H2), likely derived from multiple reassortment events, with the
      VP1, VP2, VP3 and NSP2 genes being established as novel genotypes R12, C12, M11
      and N12, respectively. Gathering sequence data on human and animal rotaviruses is
      important to trace the complex evolutionary history of atypical RVAs. 

PMID- 26205692
TI  - Primary care nurses' performance in motivational interviewing: a quantitative
      descriptive study.
AB  - BACKGROUND: Motivational interviewing is a collaborative conversational style
      intended to strengthen motivation to change. It has been shown to be effective in
      addressing many different lifestyle problems as well as in chronic disease
      management, and many disease prevention guidelines promote use of motivational
      interviewing. The aim of the present study was twofold: to assess to what extent
      the primary care nurses in the study perform motivational interviewing according
      to the Motivational Interviewing Treatment Integrity Code and to investigate how
      the participating primary care nurses rated their own performance in motivational
      interviewing. METHOD: The study was based on twelve primary care nurses' audio
      recorded motivational interviewing sessions with patients (total 32 sessions).
      After each session, the nurses completed a questionnaire regarding their
      experience of their own performance in motivational interviewing. The audio
      recorded sessions were analyzed using Motivational Interviewing Integrity Code
      3.1.1. RESULTS: None of the nurses achieved beginning proficiency in all parts of
      any motivational interviewing sessions and two nurses did not achieve beginning
      proficiency in any parts or sessions. Making more complex than simple reflections
      was the specific verbal behavior/summary score that most nurses achieved.
      Beginning proficiency/competency in "percent open questions" was the summary
      score that fewest achieved. CONCLUSION: Primary care nurses did not achieve
      beginning proficiency/competency in all aspects of motivational interviewing in
      their recorded sessions with patients, where lifestyle change was discussed. This
      indicates a need for improvement and thus additional training, feedback and
      supervision in clinical practice with motivational interviewing.

PMID- 26205693
TI  - Novel structural co-expression analysis linking the NPM1-associated ribosomal
      biogenesis network to chronic myelogenous leukemia.
AB  - Co-expression analysis reveals useful dysregulation patterns of gene
      cooperativeness for understanding cancer biology and identifying new targets for
      treatment. We developed a structural strategy to identify co-expressed gene
      networks that are important for chronic myelogenous leukemia (CML). This strategy
      compared the distributions of expressional correlations between CML and normal
      states, and it identified a data-driven threshold to classify strongly co
      expressed networks that had the best coherence with CML. Using this strategy, we
      found a transcriptome-wide reduction of co-expression connectivity in CML,
      reflecting potentially loosened molecular regulation. Conversely, when we focused
      on nucleophosmin 1 (NPM1) associated networks, NPM1 established more co
      expression linkages with BCR-ABL pathways and ribosomal protein networks in CML
      than normal. This finding implicates a new role of NPM1 in conveying tumorigenic
      signals from the BCR-ABL oncoprotein to ribosome biogenesis, affecting cellular
      growth. Transcription factors may be regulators of the differential co-expression
      patterns between CML and normal. 

PMID- 26205694
TI  - Psychometric Properties of the Spinal Cord Injury Pressure Ulcer Scale (SCIPUS)
      for Pressure Ulcer Risk Assessment During Inpatient Rehabilitation.
AB  - OBJECTIVE: To assess the psychometric properties of the Spinal Cord Injury
      Pressure Ulcer Scale (SCIPUS) for pressure ulcer (PU) risk assessment during
      inpatient rehabilitation. DESIGN: Prospective cohort. SETTING: Tertiary
      rehabilitation centers. PARTICIPANTS: Individuals (N=759) participating in
      inpatient spinal cord injury rehabilitation between January 3, 2012, and April
      23, 2014. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Admission SCIPUS
      scores and the corresponding risk stratification, PU incidence, intraclass
      correlation coefficient (ICC) for interrater reliability, sensitivity,
      specificity, and likelihood ratios (LRs). Receiver operating characteristic
      analysis was performed to calculate the area under the curve (AUC). RESULTS: Mean
      SCIPUS scores were higher for individuals who developed PUs than for those who
      did not (mean SCIPUS score, 9.8+/-2.5 vs 8.5+/-2.6). Interrater reliability was
      excellent for SCIPUS composite scores (ICC=.91) and very good for risk
      stratification (ICC=.86). Using the existing cutoff value of >=6 for "high risk"
      category, sensitivity and specificity were estimated to be .97 and .12,
      respectively, with an LR of 1.1. A cutoff value of >=8 yielded a better balance
      between sensitivity and specificity (.85 and .38, respectively). The AUC equaled
      .64 with an LR of 1.4. Results were similar when the analysis was confined to PUs
      of stage II or greater. CONCLUSIONS: The psychometric properties of the SCIPUS do
      not currently support its routine use as a measure of PU risk in individuals with
      spinal cord injury undergoing inpatient rehabilitation. LRs of <2 indicate that
      stratification as high risk or very high risk does not substantially increase the
      likelihood of identifying individuals who develop PUs beyond chance alone. AUCs
      were also below the desired cutoff value of 0.7.

PMID- 26205695
TI  - Therapeutic potential of digitoflavone on diabetic nephropathy: nuclear factor
      erythroid 2-related factor 2-dependent anti-oxidant and anti-inflammatory effect.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a therapeutic
      target in many diseases, because it can induce antioxidant enzymes and other
      cytoprotective enzymes. Moreover, some Nrf2 activators have strong anti
      inflammatory activities. Oxidative stress and inflammation are major components
      involved in the pathology of diabetic nephropathy. In the present study, we
      evaluated the Nrf2-dependent anti-oxidative and anti-inflammatory effects of
      digitoflavone in streptozotocin-induced diabetic nephropathy. The molecular
      mechanisms of digitoflavone were investigated in vitro using SV40-transformed
      mouse mesangial cells (SV40-Mes13). For the in vivo experiment, diabetes was
      induced in Nrf2+/+ and Nrf2-/- mice by STZ injection, and digitoflavone was
      administered 2 weeks after the STZ injection. Digitoflavone induced Nrf2
      activation and decreased oxidative damage, inflammation, TGF-beta1 expression,
      extracellular matrix protein expression, and mesangial cell hyperplasia in SV40
      Mes13 cells. Digitoflavone-treated Nrf2+/+ mice, but not Nrf2-/- mice, showed
      attenuated common metabolic disorder symptoms, improved renal performance,
      minimized pathological alterations, and decreased oxidative damage, inflammatory
      gene expression, inflammatory cell infiltration, TGF-beta1 expression, and
      extracellular matrix protein expression. Our results show that the anti-oxidative
      and anti-inflammatory effects of digitoflavone are mediated by Nrf2 activation
      and that digitoflavone can be used therapeutically to improve metabolic disorders
      and relieve renal damage induced by diabetes. 

PMID- 26205696
TI  - Palladium-Catalyzed Site-Selective Fluorination of Unactivated C(sp(3))-H Bonds.
AB  - The transition-metal-catalyzed direct C-H bond fluorination is an attractive
      synthetic tool toward the preparation of organofluorines. While many methods
      exist for the direct sp(3) C-H functionalization, site-selective fluorination of
      unactivated sp(3) carbons remains a challenge. Direct, highly site-selective and
      diastereoselective fluorination of aliphatic amides via a palladium-catalyzed
      bidentate ligand-directed C-H bond functionalization process on unactivated sp(3)
      carbons is reported. With this approach, a wide variety of beta-fluorinated amino
      acid derivatives and aliphatic amides, important motifs in medicinal and
      agricultural chemistry, were prepared with palladium acetate as the catalyst and
      Selectfluor as the fluorine source. 

PMID- 26205697
TI  - Review of dietary supplements for the management of osteoarthritis in dogs in
      studies from 2004 to 2014.
AB  - Osteoarthritis (OA) is a chronic, painful, degenerative and inflammatory disease
      that affects the synovial joints and leads finally to the loss of mobility. It is
      highly prevalent in dogs. Nowadays, no cure exists, and the pharmacological
      treatment is limited to clinical signs alleviation. Some positive beneficial
      effects have been highlighted with dietary supplements in the course of dog OA.
      The goals of this narrative review are to summarize the scientific data available
      in the literature on dietary supplements assessed in dog OA and to discuss some
      trails about how to improve several aspects of research and issues with dietary
      supplements, such as bioavailability and dosage regimen. Chondroitin sulphate,
      glucosamine, undenaturated type II collagen, avocado-soya bean unsaponifiables,
      curcumin and polyunsaturated fatty acids were studied in dog OA and therefore
      discussed in the present review. Most of them showed anticatabolic and anti
      inflammatory effects. Unfortunately, few data exist concerning their
      pharmacokinetics. Their bioavailability is low, but new formulations are
      developed to enhance their gastrointestinal absorption. The clinical relevance of
      these new formulations compared to native forms should be demonstrated in good
      clinical trials. Even if further investigations are needed, dietary supplements
      should be considered in OA management. 

PMID- 26205698
TI  - Anti-gp210 and anti-centromere antibodies for the prediction of PBC patients with
      an incomplete biochemical response to UDCA and bezafibrate.

PMID- 26205699
TI  - Carpal Ligament Anatomy and Biomechanics.
AB  - A fundamental understanding of the ligamentous anatomy of the wrist is critical
      for any physician attempting to treat carpal instability. The anatomy of the
      wrist is complex, not only because of the number of named structures and their
      geometry but also because of the inconsistencies in describing these ligaments.
      The complex anatomy of the wrist is described through a review of the carpal
      ligaments and their effect on normal carpal motion. Mastery of this topic
      facilitates the physician's understanding of the patterns of instability that are
      seen clinically. 

PMID- 26205700
TI  - Carpal Ligament Injuries, Pathomechanics, and Classification.
AB  - Carpal instability is a complex array of maladaptive and posttraumatic conditions
      that lead to the inability of the wrist to maintain anatomic relationships under
      normal loads. Many different classification schemes have evolved to explain the
      mechanistic evolution and pathophysiology of carpal instability, including 2 of
      the most common malalignment patterns: volar intercalated segment instability and
      the more common dorsal intercalated segment instability. Recent classifications
      emphasize the relationships within and between the rows of carpal bones. Future
      research is likely to unify the disparate paradigms used to describe wrist
      instability. 

PMID- 26205701
TI  - Perilunate Dislocations and Fracture Dislocations.
AB  - Perilunate dislocations and fracture dislocations are the result of an axial load
      with hyperextension and ulnar deviation of the wrist, combined with intercarpal
      supination. Prompt treatment injuries is essential. There is a high rate of
      missed or incorrect diagnosis. In the past, closed management was recommended.
      These methods proved to be ineffective. Current research and data show better
      results with anatomic restoration of carpal alignment and direct ligament repair.
      A combined dorsal and volar approach is preferred. This article reviews the
      current literature and discusses the surgical techniques to restore carpal
      alignment and repair the scapholunate interosseous ligament. 

PMID- 26205702
TI  - Management of Intercarpal Ligament Injuries Associated with Distal Radius
      Fractures.
AB  - The prevalence of ligamentous injury associated with fractures of the distal
      radius is reported to be as high as 69% with injury to the scapholunate
      interosseous ligament and lunotriquetral interosseous ligament occurring in 16%
      to 40% and 8.5% to 15%, respectively. There is a lack of consensus on which
      patients should undergo advanced imaging, arthroscopy, and treatment and whether
      this changes their natural history. Overall, patients with high-grade intercarpal
      ligament injuries are shown to have longer-term disability and sequelae compared
      with those with lower-grade injuries. This article reviews the diagnosis and
      treatment options for these injuries. 

PMID- 26205703
TI  - Acute Scapholunate Ligament Injuries: Arthroscopic Treatment.
AB  - Wrist arthroscopy is an effective technique for treating acute scapholunate
      instability. It allows an accurate assessment of the degree and extent of the
      ligament injury. Partial injuries are effectively treated with arthroscopic
      debridement and electrothermal ligament tightening. Complete ligament injuries
      treated arthroscopically allow direct visualization of the torn ligament and
      assessment of the degree of scaphoid displacement and rotation. The use of
      arthroscopy allows a more accurate reduction of the scaphoid and lunate at the
      time of fixation than can be obtained using just fluoroscopy. 

PMID- 26205704
TI  - Open Treatment of Acute Scapholunate Instability.
AB  - Acute treatment of scapholunate instability is important to prevent future
      complications of dorsal intercalated segment instability and scapholunate
      advanced collapse. An understanding of the fundamental normal and abnormal
      mechanics of this problem is vital. Diagnosis in the acute phase is based on
      clinical and radiographic findings and treatment focuses on primary scapholunate
      interosseous ligament repair with a reinforcing dorsal capsulodesis. Suture
      anchor repair with a modified "double-dorsal" capsulodesis is described. Current
      data show that open repair is a viable option in the acute setting with most
      patients demonstrating good to excellent functional, clinical, and radiographic
      results. 

PMID- 26205705
TI  - Chronic Scapholunate Ligament Injury: Techniques in Repair and Reconstruction.
AB  - Although the true incidence of scapholunate interosseous ligament (SLIL) injury
      is unknown, a study found that 35% of cadaveric wrists had some degree of
      scapholunate tear. Of those wrists with SLIL injury, 29% had evidence of
      arthrosis. Early recognition and treatment of these injuries can delay or prevent
      the onset of arthritis. This article details treatment options for SLIL injury
      across the spectrum of pathology with a particular emphasis on chronic
      scapholunate repair and reconstruction. New techniques and outcomes data also are
      presented. 

PMID- 26205706
TI  - Bone-Retinaculum-Bone Autografts for Scapholunate Interosseous Ligament
      Reconstruction.
AB  - Carpal instability arising from an injury to the scapholunate interosseous
      ligament (SLIL) is commonly seen and treated by hand surgeons. No technique to
      this date has proved to provide optimal results for primary repair of acute SLIL
      tear and the treatment of chronic tears of the SLIL. Recently, attention has
      shifted toward replacement of the dorsal aspect of the SLIL, which is the most
      structurally and functionally important aspect of the SLIL. This article
      describes the indications, surgical technique, postoperative treatment and
      expected results of the use of a bone-retinaculum-bone autograft procedure in the
      treatment of scapholunate instability. 

PMID- 26205707
TI  - Chronic Scapholunate Ligament Injuries: Treatment with Supplemental Fixation.
AB  - Treatment of chronic scapholunate ligament injuries can be challenging.
      Traditional reconstructive techniques, including varied capsulodeses and
      tenodeses often yield inconsistent results with loss of reduction and
      radiographic deterioration. As a result, supplemental hardware fixation has
      become more popular and may allow more robust stabilization of the scapholunate
      reconstruction. However, these procedures have complications and few data
      regarding outcomes are currently available. This article evaluates the role of
      supplemental fixation in the management of chronic scapholunate instability. 

PMID- 26205708
TI  - Diagnosis and Treatment of Acute Lunotriquetral Ligament Injuries.
AB  - Isolated acute lunotriquetral (LT) injuries are an uncommon diagnosis in hand
      surgery. Diagnosis is aided by a high index of suspicion when pain is localized
      over the LT joint. Standard radiographs show typically normal findings, leading
      to advanced diagnostic investigations, including MRI and wrist arthroscopy.
      Standard treatment options for acute LT injuries include immobilization,
      arthroscopy, and direct open LT repair. 

PMID- 26205709
TI  - Diagnosis and Treatment of Chronic Lunotriquetral Ligament Injuries.
AB  - Chronic lunotriquetral (LT) injuries are less common than scapholunate ligament
      injuries and difficult to diagnose. They may be associated with positive ulnar
      variance. Clinical diagnostic tests elicit pain at the LT interval. Although
      radiographs are typically normal, MRI and wrist arthroscopy can help confirm the
      diagnosis. When conservative treatments fail, surgical options include LT
      ligament reconstruction, LT arthrodesis, and ulnar-shortening osteotomy (in
      patients with positive ulnar variance). 

PMID- 26205710
TI  - Midcarpal Instability: A Comprehensive Review and Update.
AB  - Midcarpal instability has been well described as a clinical entity but the
      pathokinematics and pathologic anatomy continue to be poorly understood. This
      article presents a comprehensive review of the existing knowledge and literature
      based evidence for the diagnosis and management of the various entities
      comprising midcarpal instability. It discusses the limitations of the current
      understanding of midcarpal instability and proposes new directions for furthering
      knowledge of the causes and treatment of midcarpal instability and wrist
      pathomechanics in general. 

PMID- 26205711
TI  - Salvage Operations for Wrist Ligament Injuries with Secondary Arthrosis.
AB  - Wrist ligamentous injuries can be challenging to treat successfully. In some
      cases the ligament repair or reconstruction fails, resulting in instability and
      progressive degenerative changes. In other cases the original injury is missed,
      and the patient presents for the first time with established wrist arthritis.
      Multiple operations have been devised to treat patients with arthrosis secondary
      to wrist ligament injuries. This article discusses definitive salvage operations
      such as intercarpal arthrodeses and proximal row carpectomy, as well as other
      alternatives such as wrist denervation and radial styloidectomy. 

PMID- 26205712
TI  - Innovations in Intercarpal Ligament Repair and Reconstruction.

PMID- 26205713
TI  - Worth the Trip.

PMID- 26205714
TI  - Quantitative determination of target gene with electrical sensor.
AB  - Integrating loop-mediated isothermal amplification (LAMP) with capacitively
      coupled contactless conductivity detection (C(4)D), we have developed an
      electrical sensor for the simultaneous amplification and detection of specific
      sequence DNA. Using the O26-wzy gene as a model, the amount of initial target
      gene could be determined via the threshold time obtained by monitoring the
      progression of the LAMP reaction in real time. Using the optimal conditions, a
      detection limit of 12.5 copy/MUL can be obtained within 30 min. Monitoring the
      LAMP reaction by C(4)D has not only all the advantages that existing
      electrochemical methods have, but also additional attractive features including
      being completely free of carryover contamination risk, high simplicity and
      extremely low cost. These benefits all arise from the fact that the electrodes
      are separated from the reaction solution, that is C(4)D is a contactless method.
      Hence in proof of principle, the new strategy promises a robust, simple, cost
      effective and sensitive method for quantitative determination of a target gene,
      that is applicable either to specialized labs or at point-of-care. 

PMID- 26205717
TI  - A large un-ruptured abdominal aortic aneurysm causing pulmonary embolism.
AB  - A 79 years old woman presented in a peripheral hospital with dyspnea, right-sided
      pleuritic chest pain and cough for 3 days. On examination, she was tachycardiac
      and tachypneic. She had reduced air entry bilaterally on auscultation. Computed
      tomography-pulmonary angiogram, performed in peripheral Hospital, confirmed the
      diagnosis of pulmonary embolism, and she was commenced on warfarin.
      Ultrasonography showed no evidence of deep venous thrombosis in legs; however,
      ultrasound of the abdomen revealed an aortic aneurysm. She was hemodynamically
      stable on transfer to vascular surgery department, and her complete clinical
      examination revealed a pulsatile mass in the central abdomen. Computed tomography
      angiogram of aorta showed 8.7-cm abdominal aortic aneurysm. Venogram performed
      during inferior vena cava (IVC) filter insertion showed that IVC was displaced
      and compressed due to this large aortic aneurysm, causing thromboembolism. An
      open repair of the aneurysm was performed with uneventful recovery. 

PMID- 26205716
TI  - Modifiable cardiovascular risk factors in adults aged 40-79 years in Germany with
      and without prior coronary heart disease or stroke.
AB  - BACKGROUND: Control of modifiable cardiovascular disease (CVD) risk factors has
      substantially reduced CVD mortality, but risk factor levels in populations may
      change and need continuous monitoring. This study aims to provide current
      estimates of the prevalence of these risk factors in Germany according to sex and
      history of coronary heart disease (CHD) or stroke. METHODS: The analyses were
      based on data from the German Health Interview and Examination Survey for Adults
      (DEGS1; age 40-79 years, n = 5101), which is a cross-sectional population-based
      examination survey. CVD risk factors were defined according to recommendations in
      the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice
      2012. RESULTS: The mean age was 57 years and 52% were female; 493 participants
      had prior CHD and 163 participants a prior stroke. The overall prevalence of
      behavioural risk factors ranged from 17.9% for high risk alcohol consumption to
      90% for low vegetable intake. Blood pressure >= 140/90 mmHg was found in 21% and
      69% had total cholesterol >= 5.0 mmol/l. Only 16% met the targets for five
      behavioural factors combined (smoking, physical activity, fruit intake, alcohol
      intake and obesity), 13% of those with and 16% of those without CHD or stroke.
      The prevalences of most behavioural risk factors were higher among men compared
      to women. CONCLUSIONS: There is a high prevention potential from modifiable
      cardiovascular risk factors in the general population aged 40-79 years in Germany
      and among those with prior CHD or stroke. Risk factors are often co-occurring,
      are interrelated and require combined educational, behavioral, medical and policy
      approaches.

PMID- 26205715
TI  - Do We Know What Causes Eosinophilic Esophagitis? A Mechanistic Update.
AB  - The mechanisms underlying eosinophilic esophagitis (EoE) have been intensely
      investigated, and significant advances have been made in understanding the
      pathogenesis of EoE. EoE is defined as a chronic immune/antigen-mediated disease,
      characterized clinically by symptoms of esophageal dysfunction and histologically
      by an esophageal eosinophilic infiltrate. In this paper, we will review the
      current knowledge of EoE pathophysiology based on both animal and human data and
      discuss possible etiologic mechanisms from the genetic and environmental
      perspectives. EoE is a Th2-predominant inflammatory process triggered by
      allergens. Proinflammatory cytokines and chemokines recruit eosinophils and other
      effector cells, such as mast cells, into the esophageal epithelium, where they
      cause direct damage and promote esophageal remodeling. The genetic expression
      profile of EoE has been described, and several single nucleotide polymorphisms
      have been identified and associated with EoE. While this genetic contribution is
      important, it is difficult to postulate that EoE is primarily a genetic disease.
      Given the rapid epidemiologic changes in the incidence and prevalence of EoE over
      the past two decades, environmental factors may be the driving force. While it is
      not known what causes EoE in an individual patient at a specific time, the
      current hypothesis is that there is a complex interaction between genetic factors
      and environmental exposures that remains to be elucidated. 

PMID- 26205718
TI  - RhoA-Mediated Functions in C3H10T1/2 Osteoprogenitors Are Substrate Topography
      Dependent.
AB  - Surface topography broadly influences cellular responses. Adherent cell
      activities are regulated, in part, by RhoA, a member of the Rho-family of
      GTPases. In this study, we evaluated the influence of surface topography on RhoA
      activity and associated cellular functions. The murine mesenchymal stem cell line
      C3H10T1/2 cells (osteoprogenitor cells) were cultured on titanium substrates with
      smooth topography (S), microtopography (M), and nanotopography (N) to evaluate
      the effect of surface topography on RhoA-mediated functions (cell spreading,
      adhesion, migration, and osteogenic differentiation). The influence of RhoA
      activity in the context of surface topography was also elucidated using RhoA
      pharmacologic inhibitor. Following adhesion, M and N adherent cells developed
      multiple projections, while S adherent cells had flattened and widespread
      morphology. RhoA inhibitor induced remarkable longer and thinner cytoplasmic
      projections on all surfaces. Cell adhesion and osteogenic differentiation was
      topography dependent with S < M and N surfaces. RhoA inhibition increased
      adhesion on S and M surfaces, but not N surfaces. Cell migration in a wound
      healing assay was greater on S versus M versus N surfaces and RhoA inhibitor
      increased S adherent cell migration, but not N adherent cell migration. RhoA
      inhibitor enhanced osteogenic differentiation in S adherent cells, but not M or N
      adherent cells. RhoA activity was surface topography roughness dependent (S < M,
      N). RhoA activity and -mediated functions are influenced by surface topography.
      Smooth surface adherent cells appear highly sensitive to RhoA function, while
      nano-scale topography adherent cell may utilize alternative cellular signaling
      pathway(s) to influence adherent cellular functions regardless of RhoA activity.

PMID- 26205719
TI  - Behavioral and Hemodynamic Effects of Free and Protein-Bound Angiotensin IV in
      Rats in Experimental Hypo- and Hyperglycemia: Comparative Aspects.
AB  - In rats with acute hypo- and hyperglycemia the initial effects of free
      angiotensin IV and its complexes with functionally different carrier proteins
      (transport protein BSA, neuron-specific protein S100b) on hemodynamics and
      behavior of rats were qualitatively altered, in comparison with those in intact
      animals. At the same time, free angiotensin IV under conditions of hypo- and
      hyperglycemia paradoxically acquired functions of angiotensin II (moderate
      hypertension, tachycardia, polydipsia and activation of instrumental drinking
      behavior). Concurrently, complexes of angiotensin IV with BSA and S100b acquired
      functions of free angiotensin IV (hypotensia, suppression of drinking behavior).
      It is suggested that complexes of angiotensin IV with functionally different
      proteins are involved in a differentiated way first in compensation of behavior
      and hemodynamics impairment produced by acute and/or chronic hypo- and
      hyperglycemia, and then in qualitative transformation of these adaptive processes
      into stable pathological condition involving mechanisms of so called "metabolic
      memory". 

PMID- 26205720
TI  - Estimation of Functional Activity of Ionized Calcium for Complement System
      Reactivity Assessment.
AB  - We proposed a new indicator for evaluation of functional activity of Ca(2+) in
      human blood serum based on lysis of sheep erythrocytes with 10% human blood serum
      in the presence of 0.55 mM ethylene glycol tetraacetic acid at 37 degrees C for
      10 min. After incubation, the degree of sheep erythrocytes lysis inhibition is
      estimated: inhibition of complement hemolytic activity <30% is considered as high
      functional Sa(2+) activity, inhibition by 31-70% corresponds to normal activity,
      and >71% indicates low activity. The comparative studies of complement activating
      function of heterophilic antibodies, complement system reactivity in the presence
      of 0.29 M NaCl, and functional activity of ionized Ca(2+) make possible
      estimation of the individual's immune status.

PMID- 26205721
TI  - Effect of Food Load on Activities of Enzymes of the Main Metabolic Pathways in
      Blood Lymphocytes in Girls with Different Anthropometric Parameters.
AB  - Changes in enzyme activities reflecting functioning of the basic metabolic
      pathways in cells (Krebs cycle, glycolysis, pentose phosphate pathway) were
      evaluated in blood lymphocytes of girls of different somatotypes with different
      body composition under conditions of food load. A common regularity was found: a
      decrease in succinate dehydrogenase activity after meal in girls of all
      somatotypes. Specific features of individual somatotypes were also revealed. Only
      girls of athletic somatotype showed increased lactate dehydrogenase level after
      food load. Activity of glucose-6-phosphate dehydrogenase increased (more than
      twice) after food load only in girls of euryplastic somatotype. This somatotype
      is characterized by maximum values of fat and other components of the body.
      Glucose-6-phosphate dehydrogenase is the first enzyme of the pentose phosphate
      pathway; activation of this pathway accompanies enhancement of synthetic
      processes, including lipid synthesis. This can contribute to accumulation of the
      fat component (and other components) due to redistribution of substrate flows
      between metabolic pathways.

PMID- 26205722
TI  - Effect of Erythropoietin on Lymphocytes Apoptosis in Experimental Chronic Renal
      Failure.
AB  - Recombinant human erythropoietin was injected intraperitoneally in a total dose
      of 900 U/kg to rats with experimental chronic renal failure. Suspension of
      lymphocytes from animals with chronic renal failure was used in vitro,
      erythropoietin was used in concentrations of 30, 15, 7.5, 3.75, and 1.88 U/liter.
      Intact cells (Annexin-5-FITC(-)/7-AAD(-)), cells with early signs of apoptosis
      (Annexin-5-FITC(+)/7-AAD(-)), cells with late signs of apoptosis and partially
      necrotic cells (Annexin-5-FITC(+)/7-AAD(+)), as well as cells with early signs of
      necrosis (Annexin-5-FITC(-)/7-AAD(+)) were differentiated by fl ow cytometry. It
      was found that the number of peripheral blood lymphocytes with early and late
      signs of apoptosis and necrosis increased in chronic renal failure.
      Erythropoietin at a total dose of 900 U/kg reduced the number of blood
      lymphocytes with signs of apoptosis and necrosis and thus elevated the number of
      intact lymphocytes. Erythropoietin in concentrations ranging from 1.88 to 30.0
      U/liter dose dependently lowered the number of lymphocytes with early signs of
      apoptosis and the number of lymphocytes with the signs of late apoptosis and
      necrosis in vitro.

PMID- 26205723
TI  - Expression of HIF-1alpha in Multipotent Mesenchymal Stromal Cells under Hypoxic
      Conditions.
AB  - According to the data of reverse-transcription-PCR, long-term culturing of
      multipotent mesenchymal stromal cells from human adipose tissue at 1% O2 (vs.
      standard 20% O2) led to a decrease in HIF-1alpha gene expression, while no
      changes in this parameter were revealed at 5% O2. Analysis of the time course of
      HIF-1alpha mRNA level showed that at the early terms of hypoxic exposure, the
      expression of this gene increased and the duration of this increase depended on
      the severity of hypoxia. 

PMID- 26205724
TI  - Effects of a New Glutamic Acid Derivative on Myocardial Contractility of Stressed
      Animals under Conditions of Nitric Oxide Synthesis Blockade.
AB  - Glufimet (glutamic acid derivative) in a dose of 28.7 mg/kg limited the reduction
      of the cardiac functional reserve in animals subjected to 24-h stress under
      conditions of nonselective NO synthase blockade with L-NAME (10 mg/kg).
      Adrenoreactivity and increased afterload tests showed that the increment of
      myocardial contraction/relaxation rates, left-ventricular pressure, and HR were
      significantly higher in glufimet-treated stressed animals with NO synthesis
      blockade than in animals which received no glufimet. The efficiency of glufimet
      was higher than that of phenibut (the reference drug). 

PMID- 26205725
TI  - Thymic Structures Containing Somatostatin.
AB  - Double immunofluorescent staining confirmed co-expression of somatostatin
      (neuropeptide) and antigen-presenting cells of macrophage origin expressing major
      histocompatibility complex class II molecules in the intact thymus. The results
      confirmed cooperation of the neuropeptide and immunocompetent systems. 

PMID- 26205726
TI  - Molecular Factors of Cytokine-Dependent Activation of T Cells in Pulmonary
      Tuberculosis.
AB  - The parameters characterizing antituberculous immune response at the stage of
      cytokinedependent activation of T cells were analyzed in 90 patients with
      pulmonary tuberculosis before etiotropic therapy. Immunophenotyping of T cells
      for IL-12Rbeta2, WSX-1, and gp130 surface markers and T-bet intracellular
      transcription factor was carried out after specific IL-12/IL-27 induction of
      cells in vitro. An increase in the counts of CD3(+)T-bet(+), CD3(+)IL-12Rbeta2
      (+), and CD3(+)WSX-1(+)gp130(+) cells and the level of T cells with high
      expression of WSX-1 inhibitory molecule (CD3(+)WSX-1(hi+)gp130(-) and CD3(+)WSX
      1(hi+)gp130(+)) was detected. The type of disorders in the inductive stage of
      antituberculous immune response did not depend on the clinical form of disease. 

PMID- 26205727
TI  - The Relationship between Albumin-Binding Capacity of Recombinant Polypeptide and
      Changes in the Structure of Albumin-Binding Domain.
AB  - Many bacteria express surface proteins interacting with human serum albumin
      (HSA). One of these proteins, PAB from anaerobic bacteria, contains an albumin
      binding domain consisting of 45 amino acid residues known as GA domain. GA
      domains are also found in G proteins isolated from human streptococcal strains
      (groups C and G) and of albumin-binding protein isolated from group G
      streptococcal strains of animal origin. The GA domain is a left-handed three
      helix bundle structure in which amino acid residues of the second and third
      helixes are involved in albumin binding. We studied the relationship between HSA
      binding activity of the recombinant polypeptide isolated from group G
      streptococcus of animal origin and structure of the GA domain is studied.
      Structural changes in GA domain significantly attenuated HAS-binding capacity of
      the recombinant polypeptide. Hence, affinity HSA-binding polypeptide depends on
      stability of GA domain structure. 

PMID- 26205728
TI  - Morphological Evaluation of Oxidative Phosphorylation System in Myocardial
      Infarction under Conditions of Modified Vascular Endothelial Growth Factor
      Concentration.
AB  - The relationship between vascular endothelium growth factor (VEGF) and
      cardiomyocyte oxidative phosphorylation level in experimental myocardial
      infarction, caused by diathermocoagulation of the periconical ventricular artery,
      was studied by immunofluorescent microscopy. Staining showed uneven distribution
      of cytochrome c in the mitochondria in the focus of myocardial infarction 2 h
      after the operation. After 24 h uneven staining of cardiomyocytes was found in
      the peri-infarction zone and no staining in the zone of myocardial infarction.
      This indicated a significant decrease in the level of redox enzymes. This picture
      persisted till day 14. Intraventricular injection of VEGF to animals led to a
      significant increase of the immunohistochemical reaction intensity, which reached
      the peak by day 7. The distribution of immunohistochemical reaction products
      under conditions of VEGF blocking was about the same as in spontaneous
      postinfarction reparative restitution. Our data indicated that increase of VEGF
      concentration in the myocardium maintained and stimulated oxidative
      phosphorylation in cardiomyocytes during the postinfarction period. 

PMID- 26205729
TI  - Absolute quantification of dengue virus serotype 4 chimera vaccine candidate in
      Vero cell culture by targeted mass spectrometry.
AB  - Infection by dengue flavivirus is transmitted by mosquitoes and affects tens to
      hundreds of millions people around the world each year. Four serotypes have been
      described, all of which cause similar disease. Currently, there no approved
      vaccines or specific therapeutics for dengue, although several vaccine prototypes
      are in different stages of clinical development. Among them, a chimeric vaccine,
      built from the replication machinery of the yellow fever 17D virus, has shown
      promising results in phase III trials. Accurate quantitation of expressed viral
      particles in alive attenuated viral antigen vaccine is essential and
      determination of infectious titer is usually the method of choice. The current
      paper describes an alternative or orthogonal strategy, namely, a multiplexed and
      absolute assay of four proteins of the chimera yellow fever/dengue serotype 4
      virus using targeted MS in SRM mode. Over 1 month, variability of the assay using
      a partially purified Vero cell extract was between 8 and 17%, and accuracy was
      between 80 and 120%. In addition, the assay was linear between 6.25 and 200
      nmol/L and could therefore be used in the near future to quantify dengue virus
      type 4 during production and purification from Vero cells. 

PMID- 26205731
TI  - Determinants for Quantitative Sensory Testing and the Association with Chronic
      Musculoskeletal Pain in the General Elderly Population.
AB  - OBJECTIVE: Chronic musculoskeletal pain is accompanied by central sensitization,
      which can be determined with quantitative sensory testing (QST). In this study,
      we aim to investigate whether central sensitization, as measured by thermal QST,
      is detectable in community-dwelling elderly individuals suffering from self
      reported chronic pain and identify determinants influencing thermal QST
      measurement analyses and interpretation. METHODS: In 3,936 participants of the
      Rotterdam Study, cold and warmth sensitivity and heat pain thresholds were
      determined using the thermo-sensory analyzer TSA II (Medoc Advanced Medical
      Systems, Durham, NC, U.S.A.). Using Cox regression, associations were studied
      with chronic pain and potential determinants (body mass index [BMI], reaction
      speed, systolic and diastolic blood pressure, skin color, skin temperature,
      seasonal influence, depression, anxiety, atopic eczema, age at menarche, years
      since menopause, hormone replacement therapy (HRT) use during menopause, and
      reproductive lifespan). RESULTS: In addition to the effect of age and gender on
      thermal sensitivity, darker skin color and the presence of atopic eczema were
      associated with higher sensitivity for heat pain. Cold sensitivity and warmth
      sensitivity thresholds were both influenced by BMI, reaction speed, skin
      temperature, season, depression, dark skin color, years since menopause, and
      reproductive lifespan. The presence of chronic pain was associated with 0.2
      degrees lower heat pain threshold in all participants, and 0.3 degrees lower in
      individuals with chronic pain in more than 2 sites. CONCLUSION: Higher
      sensitivity for heat pain, one feature of central sensitization, is present in
      community-dwelling elderly with chronic pain. Additional determinants should be
      considered when analyzing and interpreting QST measurements.

PMID- 26205732
TI  - Synthesis, characterization, photophysical properties, and catalytic activity of
      an SCS bis(N-heterocyclic thione) (SCS-NHT) Pd pincer complex.
AB  - Treatment of 1,3-bis(3'-butylimidazolyl-1'-yl)benzene diiodide with elemental
      sulfur in the presence of a base produced a bis(N-heterocyclic thione) (NHT)
      pincer ligand precursor. Its reaction with PdCl2(CH3CN)2 produced chloro[1,3
      bis(3'-butylimidazole-2'-thione-kappa-S)benzene-kappa-C]palladium(ii), a 6,6
      fused ring SCS-NHT palladium pincer complex. This air stable compound is, to our
      knowledge, the first SCS pincer complex that utilizes N-heterocyclic thione (NHT)
      donor groups. The molecular structures of the ligand precursor and the palladium
      complex were determined by X-ray crystallography and computational studies
      provided insight into the interconversion between its rac and meso conformations.
      The photophysical properties of the complex were established, and its catalytic
      activity in Suzuki, Heck, and Sonogashira cross-coupling reactions was evaluated.

PMID- 26205733
TI  - Watching paint dry; more exciting than it seems.
AB  - With an ever-increasing demand for sustainable alternatives to solvent-borne
      coatings and paints, the pressure to develop aqueous alternatives that match or
      exceed the performance of their traditional counterparts rises. A crucial step in
      this sustainability challenge for the years to come is to arrive at a deep, and
      complete, understanding of how aqueous paints dry and form their final protective
      films. As it turns out, this is no minor challenge. Yet, understanding drying and
      film formation is a prototypical soft matter problem at heart, displaying a rich
      variety of complex non-equilibrium phenomena that are waiting to be understood.
      Watching paint dry is far from the boring activity the saying suggests. 

PMID- 26205734
TI  - Adjuvant argon-based cryoablation for joint-preserving tumor resection in
      patients with juxta-articular osteosarcoma around the knee.
AB  - BACKGROUNDS: Opinion remains controversial as to whether joint-saving surgery
      could be safely performed in patients with juxta-articular osteosarcoma. The aim
      of this study was to assess the validity of adjuvant cryosurgery in joint salvage
      surgery. METHODS: We evaluated the oncological and functional outcomes of
      patients who underwent joint-sparing surgery in which argon-based cryoablation
      was employed to aid partial epiphysis-preserved tumor resection for osteosarcoma
      around the knee (7 in proximal tibia, 5 in distal femur). RESULTS: The study
      included 12 patients (5 male, 7 female, mean age 15.8 years (11-24). At a mean
      follow-up of 48.4 months (38-61), lung metastasis occurred in three patients.
      Among these, one patient had died, one was alive with disease, and one had no
      evidence of disease after lobectomy. Histological examination of the resected
      specimens revealed no viable tumor at the osteotomy plane. There was no local
      recurrence in the residual epiphysis except one in soft tissue. The mean
      Musculoskeletal Tumor Society functional score was 92.7%. CONCLUSIONS: Argon
      based cryosurgery is a reliable method of sterilizing the tumor in the epiphysis
      thus allowing safe joint-saving tumor resection possible in patients with juxta
      articular osteosarcoma.

PMID- 26205735
TI  - Trabeculectomy ab interno with the Trabectome(r) as a therapeutic option for
      uveitic secondary glaucoma.
AB  - PURPOSE: Treatment of secondary glaucoma in uveitis patients is challenging.
      Owing to the young age of these patients, sufficient lowering of the intraocular
      pressure (IOP) is essential to prevent progression of visual field loss. However,
      because of the chronic inflammatory stimulus, filtration surgery has an increased
      risk of failure, especially in patients who have previously undergone surgery.
      Therefore, minimally invasive glaucoma surgery is a valuable alternative.
      METHODS: The clinical records of 24 consecutive patients with uveitic secondary
      glaucoma who underwent trabeculectomy ab interno with the Trabectome(r) at the
      Eye Center of the Albert-Ludwigs University of Freiburg between June 2009 and
      June 2014 (registered in the Freiburg trabectome database) were retrospectively
      analyzed. The general baseline information for each patient included age, gender,
      glaucoma type, ocular medication and current IOP. The postoperative IOP and
      number of antiglaucomatous medications were recorded at each visit. Statistical
      analyses were performed using the Kaplan-Meier estimator and Dunnett's t-test.
      RESULTS: The mean IOP before surgery was 31 +/- 6.7 mmHg (median 32 mmHg). Both
      the IOP and the number of medications significantly decreased over the various
      follow-up intervals after trabeculectomy ab interno with the Trabectome(r).
      Patients with follow-ups continuing past one year showed an IOP-reduction of
      approximately 40 % and a medication number reduction from 2 to 0.67. The failure
      rate (necessitating further glaucoma surgery) was N = 3 (12.5 %) patients.
      CONCLUSIONS: Trabeculectomy ab interno with the Trabectome(r) is a minimally
      invasive and effective method for controlling IOP in uveitic secondary glaucoma.

PMID- 26205737
TI  - Drug-Related Pneumonitis During Mammalian Target of Rapamycin Inhibitor Therapy:
      Radiographic Pattern-Based Approach in Waldenstrom Macroglobulinemia as a
      Paradigm.
AB  - BACKGROUND: This study determined the frequency of drug-related pneumonitis
      during mammalian target of rapamycin (mTOR) inhibitor therapy in Waldenstrom
      macroglobulinemia patients and investigated the imaging characteristics and
      radiographic patterns of pneumonitis. MATERIALS AND METHODS: A total of 40
      patients (23 men, 17 women; 43-84 years old) with Waldenstrom macroglobulinemia
      treated in 2 trials of the mTOR inhibitor everolimus were retrospectively
      studied. Chest computed tomography (CT) scans during therapy were reviewed for
      abnormalities suspicious for drug-related pneumonitis by the consensus of three
      radiologists, evaluating the extent, distributions, and specific findings. The
      radiographic patterns of pneumonitis were classified using the American Thoracic
      Society/European Respiratory Society classification of interstitial pneumonia.
      RESULTS: Drug-related pneumonitis was noted in 23 patients (58%). The median time
      from the initiation of therapy to the onset of pneumonitis was 5.7 months. Lower
      lungs were involved in all 23 patients, with a higher extent than in the other
      zones (p < .001). The distribution was peripheral and lower in 11 patients (48%)
      and mixed and multifocal in 10 (44%). The findings were bilateral in 20 patients
      (87%). Ground glass opacities (GGOs) and reticular opacities were present in all
      23 patients, with consolidation in 12, traction bronchiectasis in 2, and
      centrilobular nodularity in 1. The pattern of pneumonitis was classified as
      cryptogenic organizing pneumonia (COP) in 16 (70%) and nonspecific interstitial
      pneumonia (NSIP) in 7 (30%), with overlapping features of COP and NSIP in 7
      patients. CONCLUSION: Drug-related pneumonitis was noted on CT in 58% of
      Waldenstrom macroglobulinemia patients treated with mTOR inhibitor therapy. Most
      common findings were bilateral GGOs and reticular opacities, with or without
      consolidation, in peripheral and lower lungs, demonstrating COP and NSIP
      patterns. IMPLICATIONS FOR PRACTICE: The present study has demonstrated that drug
      related pneumonitis during mammalian target of rapamycin (mTOR) inhibitor therapy
      is highly frequent, occurring in 58% of patients with Waldenstrom
      macroglobulinemia. The radiographic patterns of pneumonitis demonstrated
      cryptogenic organizing pneumonia and nonspecific interstitial pneumonia patterns,
      with overlapping features in 30% of the patients. The present study describes an
      initial attempt of a radiographic pattern-based approach to drug-related
      pneumonitis in the era of molecular targeting therapy, with a cohort of patients
      with Waldenstrom macroglobulinemia receiving mTOR inhibitor therapy as a
      paradigm, which might contribute to further understanding and in-depth
      interpretation of lung toxicity during novel cancer therapy.

PMID- 26205736
TI  - Implementation of a Molecular Tumor Board: The Impact on Treatment Decisions for
      35 Patients Evaluated at Dartmouth-Hitchcock Medical Center.
AB  - BACKGROUND: Although genetic profiling of tumors is a potentially powerful tool
      to predict drug sensitivity and resistance, its routine use has been limited
      because clinicians are often unfamiliar with interpretation and incorporation of
      the information into practice. We established a Molecular Tumor Board (MTB) to
      interpret individual patients' tumor genetic profiles and provide treatment
      recommendations. PATIENTS AND METHODS: DNA from tumor specimens was sequenced in
      a Clinical Laboratory Improvement Amendments-certified laboratory to identify
      coding mutations in a 50-gene panel (n = 34) or a 255-gene panel (n = 1). Cases
      were evaluated by a multidisciplinary MTB that included pathologists,
      oncologists, hematologists, basic scientists, and genetic counselors. RESULTS:
      During the first year, 35 cases were evaluated by the MTB, with 32 presented for
      recommendations on targeted therapies, and 3 referred for potential germline
      mutations. In 56.3% of cases, MTB recommended treatment with a targeted agent
      based on evaluation of tumor genetic profile and treatment history. Four patients
      (12.5%) were subsequently treated with a MTB-recommended targeted therapy; 3 of
      the 4 patients remain on therapy, 2 of whom experienced clinical benefit lasting
      >10 months. CONCLUSION: For the majority of cases evaluated, the MTB was able to
      provide treatment recommendations based on targetable genetic alterations. The
      most common reasons that MTB-recommended therapy was not administered stemmed
      from patient preferences and genetic profiling at either very early or very late
      stages of disease; lack of drug access was rarely encountered. Increasing
      awareness of molecular profiling and targeted therapies by both clinicians and
      patients will improve acceptance and adherence to treatments that could
      significantly improve outcomes. IMPLICATIONS FOR PRACTICE: Case evaluation by a
      multidisciplinary Molecular Tumor Board (MTB) is critical to benefit from
      individualized genetic data and maximize clinical impact. MTB recommendations
      shaped treatment options for the majority of cases evaluated. In the few patients
      treated with MTB-recommended therapy, disease outcomes were positive and support
      genetically informed treatment.

PMID- 26205739
TI  - Dermoscopic Visualization of Vellus Hair Involvement in Tinea Corporis: A
      Criterion for Systemic Antifungal Therapy?
AB  - Dermoscopy has been shown to be a valuable tool in the diagnosis and monitoring
      of several infectious diseases. We report a case of tinea corporis in an infant
      in whom dermoscopy helped us to determine vellus hair involvement, causing
      treatment to be switched from topical to systemic antifungal therapy. 

PMID- 26205738
TI  - Financial Distress and Its Associations With Physical and Emotional Symptoms and
      Quality of Life Among Advanced Cancer Patients.
AB  - OBJECTIVE: There are limited data on the effects of financial distress (FD) on
      overall suffering and quality of life (QOL) of patients with advanced cancer
      (AdCa). In this cross-sectional study, we examined the frequency of FD and its
      correlates in AdCa. PATIENTS AND METHODS: We interviewed 149 patients, 77 at a
      comprehensive cancer center (CCC) and 72 at a general public hospital (GPH). AdCa
      completed a self-rated FD (subjective experience of distress attributed to
      financial problems) numeric rating scale (0 = best, 10 = worst) and validated
      questionnaires assessing symptoms (Edmonton Symptom Assessment System [ESAS]),
      psychosocial distress (Hospital Anxiety and Depression Scale [HADS]), and QOL
      (Functional Assessment of Cancer Therapy-General [FACT-G]). RESULTS: The
      patients' median age was 60 years (95% confidence interval [CI]: 58.6-61.5
      years); 74 (50%) were female; 48 of 77 at CCC (62%) versus 13 of 72 at GPH (18%)
      were white; 21 of 77 (27%) versus 32 of 72 (38%) at CCC and GPH, respectively,
      were black; and 7 of 77 (9%) versus 27 of 72 (38%) at CCC and GPH, respectively,
      were Hispanic (p < .0001). FD was present in 65 of 75 at CCC (86%; 95% CI: 76%
      93%) versus 65 of 72 at GPH (90%; 95% CI: 81%-96%; p = .45). The median intensity
      of FD at CCC and GPH was 4 (interquartile range [IQR]: 1-7) versus 8 (IQR: 3-10),
      respectively (p = .0003). FD was reported as more severe than physical distress,
      distress about physical functioning, social/family distress, and emotional
      distress by 45 (30%), 46 (31%), 64 (43%), and 55 (37%) AdCa, respectively (all
      significantly worse for patients at GPH) (p < .05). AdCa reported that FD was
      affecting their general well-being (0 = not at all, 10 = very much) with a median
      score of 5 (IQR: 1-8). FD correlated (Spearman correlation) with FACT-G (r = 
      0.23, p = .0057); HADS-anxiety (r = .27, p = .0014), ESAS-anxiety (r = .2, p =
      .0151), and ESAS-depression (r = .18, p = .0336). CONCLUSION: FD was very
      frequent in both groups, but median intensity was double among GPH patients. More
      than 30% of AdCa rated FD to be more severe than physical, family, and emotional
      distress. More research is needed to better characterize FD and its correlates in
      AdCa and possible interventions. IMPLICATIONS FOR PRACTICE: Financial distress is
      an important and common factor contributing to the suffering of advanced cancer
      patients and their caregivers. It should be suspected in patients with
      persistent, refractory symptom expression. Early identification, measurement, and
      documentation will allow clinical teams to develop interventions to improve
      financial distress and its impact on quality of life of advanced cancer patients.

PMID- 26205740
TI  - Parenting in mothers with borderline personality disorder and impact on child
      outcomes.
AB  - QUESTION: This systematic review explores two questions: what parenting
      difficulties are experienced by mothers with borderline personality disorder
      (BPD); and what impact do these have on her children? STUDY SELECTION AND
      ANALYSIS: Studies had to include mothers with a diagnosis of BPD, who was the
      primary caregiver to a child/children under 19 years. PsycINFO and MEDLINE were
      screened (update: July 2014), yielding 17 relevant studies. FINDINGS: Mothers
      with BPD are often parenting in the context of significant additional risk
      factors, such as depression, substance use and low support. Interactions between
      mothers with BPD and their infants are at risk of low sensitivity and high
      intrusiveness, and mothers have difficulty in correctly identifying their
      emotional state. Levels of parenting stress are high, and self-reported
      competence and satisfaction are low. The family environment is often hostile and
      low in cohesion, and mothers with BPD show low levels of mind-mindedness but high
      levels of overprotection of older children. Outcomes for children are poor
      compared with both children of healthy mothers, and mothers with other disorders.
      Infants of mothers with BPD have poorer interactions with their mother (e.g.,
      less positive affect and vocalising, more dazed looks and looks away). Older
      children exhibit a range of cognitive-behavioural risk factors (e.g., harm
      avoidance, dysfunctional attitudes and attributions), and have poorer
      relationships with their mothers. Unsurprisingly, given these findings, children
      of mothers with BPD have poorer mental health in a range of domains. CONCLUSIONS:
      This review highlights the elevated need for support in these mother-child dyads.

PMID- 26205741
TI  - Which drug is the best bet when your bipolar patient gets depressed?

PMID- 26205742
TI  - Computerised cognitive behavioural therapy has the potential to prevent and treat
      anxiety and depression in young people.

PMID- 26205743
TI  - [Importance of the Watzke-Allen test in diagnostics and staging of macular
      holes].
AB  - BACKGROUND: The Watzke-Allen test (WAT) is a simple diagnostic tool designed for
      the diagnosis of full thickness macular holes (FTMH) but due to the rapid
      progress of imaging diagnostics it was replaced by spectral domain optical
      coherence tomography (SD-OCT) of macular pathologies. The aim of this study was
      to examine if the WAT is able to distinguish between the different FTMH stages.
      METHODS: In 57 eyes of 57 patients with clinical evidance of FTMH, the WAT was
      first performed followed by SD-OCT examination and a distinction was made between
      a negative (slit beam normal) and a positive sign (slit beam modified as groove
      and hourglass configuration or completely broken). RESULTS: In 49 out of 57
      patients the WAT was positive (hourglass 46 patients and broken 3 patients).
      Based on the SD-OCT results the following diagnoses were made: lamellar macular
      holes (LMH, 3 patients), vitreomacular traction (VMT, 4 patients), small macular
      hole (<= 250 um,  5 patients), medium sized macular hole (250-400 um, 11
      patients) and large macular hole (>= 400 um,  34 patients). In 91 % of the
      patients with medium and large FTMH, the WAT was positive, whereas the WAT was
      positive in only 67 % of patients with small FTMH, VMT and LMH. The sensitivity
      for large and medium FTMH was 93 % but the specificity was only 33 %. CONCLUSION:
      The WAT was positive in a high percentage of patients with large and medium sized
      macular holes as well as patients with small macular holes and LMH. The
      sensitivity of certain indications for treatment was 93 % but the specificity was
      only 33 %; therefore, the WAT alone is not suitable for a certain preoperative
      differentiation of macular alterations.

PMID- 26205744
TI  - [Prolonged topical natamycin 5 % therapy before and after keratoplasty for
      Fusarium keratitis].
AB  - CASE REPORT: A 69-year-old female patient presented with a therapy-resistant
      corneal ulcer due to contact lenses, which had been present in the left eye for 1
      month. The best corrected visual acuity at the first visit was 0.2. Keratitis
      with a central corneal ulcer was found. A corneal curettage was performed
      followed by inpatient therapy with antibiotic eye drops. The first PCR result was
      negative and the microbiological culture was sterile after 48 h. The clinical
      findings improved during the hospital stay. There was a decrease in the size of
      the corneal ulcer and an increase of best corrected visual acuity up to 0.4 so
      that the patient was discharged. COURSE: After 8 weeks the patient presented
      again with a painful eye and visual decline to 0.1. The left eye showed a
      fulminant keratitis with corneal abscess so that a second course of therapy was
      initiated. The PCR of the second corneal curettage was positive for Fusarium.
      Antifungal therapy with natamycin 5 % eye drops (via the international pharmacy)
      and systemic antifungal therapy with voriconazole (2 * 200 mg) were initiated.
      Due to personal circumstances the patient rejected corneal transplantation,
      therefore, local and systemic antifungal outpatient treatment was continued for
      another 2 months until keratoplasty a chaud of the left eye could be performed.
      At this time there was a clear reduction of inflammation but a descemetocele
      developed. The patient was treated with local and systemic antifungal therapy
      (under control of liver and kindney parameters in blood) for 3 months
      postoperatively in addition to administration of local and systemic steroids.
      DIAGNOSTICS: In cases of therapy-resistant keratitis, a Fusarium keratitis should
      always be considered. Corneal curettage ahead of therapy is very important.
      THERAPY: Natamycin 5 % eye drops are the first choice of topical antifungal
      medication in cases of Fusarium keratitis. Even though intensive local and
      systemic therapy are performed, patients often require corneal transplantation.
      Due to a high rate of recurrence a longer local and systemic antifungal therapy
      is required. CONCLUSION: In the case described here, there was a clear corneal
      graft without Fusarium recurrence 1 year after surgery and it is presumed the
      prolonged antifungal therapy before and after surgery was an important factor for
      this clinical outcome.

PMID- 26205745
TI  - [Unclear retinopathy after intravitreal injection of ocriplasmin].
AB  - CASE REPORT: This article reports the case of a 50-year-old female patient who
      presented with reduced visual acuity of 0.8 p and metamorphopsia of the left eye
      caused by focal vitreomacular traction and who was treated with intravitreal
      Jetrea(r) (ocriplasmin). After injection the patient suffered from progressive
      nyctalopia and visual field defects. Electroretinography (ERG) showed decreased
      amplitudes and optical coherence tomography (OCT) showed decreased reflectivity
      in the ellipsoid layer that persisted for 2 months after treatment. CONCLUSION:
      Before injection of Jetrea(r) a detailed clarification of such potential side
      effects is necessary to increase patient compliance in the follow-up.

PMID- 26205746
TI  - Exenatide and Sitagliptin Decrease Interleukin 1beta, Matrix Metalloproteinase 9,
      and Nitric Oxide Synthase 2 Gene Expression But Does Not Reduce Alveolar Bone
      Loss in Rats With Periodontitis.
AB  - BACKGROUND: New drugs for the treatment of diabetes, glucagon-like peptide-1 (GLP
      1) receptor agonists and inhibitors of dipeptidyl peptidase-4 (DPP-4) have shown
      pleiotropic effects on bone metabolism and anti-inflammatory properties. The aim
      of this study is to evaluate the effects of exenatide (GLP-1 agonist) and
      sitagliptin (DPP-4 inhibitor) during periodontitis induction by ligature
      insertion in rats. METHODS: Forty rats were divided into four groups: 1) animals
      with induced periodontitis that received exenatide (EG); 2) animals with induced
      periodontitis that received sitagliptin (SG); 3) animals with induced
      periodontitis and without drug treatment (LG); and 4) animals without induced
      periodontitis and without drug treatment (controls). The drugs were administered
      for 28 days. On the day the animals were sacrificed, blood was collected for
      analysis of glucose and DPP-4 levels. The gene expressions of prostaglandin
      endoperoxide synthase 2, tissue inhibitor of metalloproteinase 1, Dpp4, nitric
      oxide synthase 2 (Nos2), interleukin 1beta (Il1b), and matrix metalloproteinase 9
      (Mmp9) in the gingiva; support and alveolar bone loss; connective tissue
      attachment; and the quantity of gingival collagen were evaluated. RESULTS:
      Exenatide and sitagliptin treatments have led to a lower percentage of weight
      gain but did not influence glycemia. Sitagliptin reduced the serum concentration
      of DPP-4. Interestingly, although the gene expression profile has revealed a
      downregulation of Mmp9, Nos2, and Il1b in both EG and SG compared to LG, a
      significant protective effect was not observed on alveolar bone and collagen
      tissue in this model. CONCLUSION: Regardless of the reduction of the expression
      of Il1b, Nos2, and Mmp9, the drugs were not effective in the stabilization or
      reduction of alveolar bone loss and collagen degradation in rats.

PMID- 26205747
TI  - Effect of Non-Surgical Periodontal Treatment on Clinical and Biochemical Risk
      Markers of Cardiovascular Disease: A Randomized Trial.
AB  - BACKGROUND: Various studies have shown periodontal disease is one of the risk
      factors for coronary heart disease (CHD), and periodontal treatment of patients
      with CHD has also been correlated with reduction in systemic markers of CHD. The
      aim of this study is to evaluate the effect of non-surgical periodontal treatment
      (NSPT) on the cardiovascular clinical and biochemical status of patients with
      CHD. METHODS: Seventy known patients with CHD were allocated randomly to either a
      control group (C; no periodontal therapy) (n = 35) or an experimental group (E;
      NSPT in the form of scaling and root planing [SRP]) (n = 35). Cardiovascular
      status was assessed using clinical parameters such as pulse, respiratory rate,
      blood pressure (BP), and biochemical parameters, such as high-sensitivity C
      reactive protein (hsCRP), lipid profile, and white blood cell (WBC) count, at
      baseline and 1, 3, and 6 months. Intergroup and intragroup comparisons were
      performed using Student t test, and P <0.05 was considered statistically
      significant. RESULTS: The complete data at the end of the study were provided by
      only 55 patients (group C, n = 25; group E, n = 30). Highly statistically
      significant reduction was observed in systolic BP (7.1 mm Hg) and very-low
      density lipoproteins (VLDLs; 5.16 mg/dL) in group E. Changes were also observed
      in other cardiovascular biochemical and clinical parameters but were not
      statistically significant. CONCLUSIONS: NSPT (in the form of SRP) positively
      affects limited cardiovascular (clinical and biochemical) status of patients with
      CHD. Reduction in triglyceride, VLDL, total WBC, lymphocyte, and neutrophil
      counts and increase in hsCRP, total cholesterol, high-density lipoprotein, and
      low-density lipoprotein levels were observed. Highly significant reduction in
      VLDL cholesterol levels and systolic BP was observed among the various parameters
      measured.

PMID- 26205748
TI  - Declaration and Handling of Conflicts of Interest in Guidelines: A Study of S1
      Guidelines From German Specialist Societies From 2010-2013.
AB  - BACKGROUND: Authors' conflicts of interest may affect the content of medical
      guidelines. In April 2010, the Association of Scientific Medical Societies in
      Germany (AWMF) issued recommendations on how such conflicts of interest should be
      dealt with. Most AWMF guidelines are so-called S1 guidelines developed by
      informal consensus in a group of experts. We now present the first study to date
      on the management of conflicts of interest in S1 guidelines. METHODS: On 2
      December 2013, we selected the guidelines that had appeared from 1 November 2010
      to 1 November 2013 among the 449 current S1 guidelines on the AWMF website. We
      extracted information about conflicts of interest from the guideline texts,
      reports, and/or conflict of interest statements and evaluated this information
      descriptively. RESULTS: There were 234 S1 guidelines in this category, developed
      by a total of 2190 experts. For 7% (16/234) of the guidelines and 16% (354/2190)
      of the experts, no individual conflict of interest statement could be found.
      Where conflict of interest statements were available, conflicts of interest were
      often declared--in 98% (213/218) of the guidelines and by 85% (1565/1836) of the
      authors. The most common type of conflict of interest was membership in a
      specialist society or professional association (1571/1836, 86%). Half of the
      experts acknowledged a financial conflict of interest (911/1836, 50%). Conflicts
      of interest were more common among experts contributing to guidelines that mainly
      concerned treatment with drugs or other medical products than in guidelines that
      did not have an emphasis of this type (397/663, or 60%, versus 528/1173, or 45%).
      The conflicts of interest were assessed in 11% (25/234) of the guidelines, with
      practical consequences in a single case. CONCLUSION: Conflicts of interest are
      often declared in the S1 guidelines of the AWMF, but they are only rarely
      assessed by external evaluators. Clear rules should be issued for how experts'
      declared conflicts of interest should be acted upon, whether they are of a
      financial nature or not.

PMID- 26205749
TI  - The Treatment of Well-Differentiated Thyroid Carcinoma.
AB  - BACKGROUND: Recent decades have seen a rise in the incidence of well
      differentiated (mainly papillary) thyroid carcinoma around the world. In Germany,
      the age-adjusted incidence of well-differentiated thyroid carcinoma in 2010 was
      3.5 per 100 000 men and 8.7 per 100 000 women per year. METHODS: This review is
      based on randomized, controlled trials and multicenter trials on the treatment of
      well-differentiated thyroid carcinoma that were retrieved by a selective
      literature search, as well as on three updated guidelines issued in the past two
      years. RESULTS: The recommended extent of surgical resection depends on whether
      the tumor is classified as low-risk or high-risk, so that papillary
      microcarcinomas, which carry a highly favorable prognosis, will not be
      overtreated. More than 90% of localized, well-differentiated thyroid carcinomas
      can be cured with a combination of surgery and radioactive iodine therapy.
      Radioactive iodine therapy is also effective in the treatment of well
      differentiated thyroid carcinomas with distant metastases, yielding a 10-year
      survival rate of 90%, as long as there is good iodine uptake and the tumor goes
      into remission after treatment; otherwise, the 10-year survival rate is only 10%.
      In the past two years, better treatment options have become available for
      radioactive-iodine-resistant thyroid carcinoma. Phase 3 studies of two different
      tyrosine kinase inhibitors have shown that either one can markedly prolong
      progression-free survival, but not overall survival. Their more common clinically
      significant side effects are hand-foot syndrome, hypertension, diarrhea,
      proteinuria, and weight loss. CONCLUSION: Slow tumor growth, good resectability,
      and susceptibility to radioactive iodine therapy lend a favorable prognosis to
      most cases of well-differentiated thyroid carcinoma. The treatment should be risk
      adjusted and interdisciplinary, in accordance with the current treatment
      guidelines. Even metastatic thyroid carcinoma has a favorable prognosis as long
      as there is good iodine uptake. The newly available medical treatment options for
      radioactive-iodine-resistant disease need to be further studied.

PMID- 26205750
TI  - Modifying Behaviors in Patients With Coronary Heart Disease.

PMID- 26205751
TI  - Evaluation Does Exist.

PMID- 26205752
TI  - In Reply.

PMID- 26205753
TI  - Importance of Psychological Care.

PMID- 26205754
TI  - Gender Dichotomy Is Culturally Determined.

PMID- 26205755
TI  - In Reply.

PMID- 26205756
TI  - The 5-HT4 Agonist Prucalopride Stimulates L-DOPA-Induced Dopamine Release in
      Restricted Brain Regions of the Hemiparkinsonian Rat In Vivo.

PMID- 26205757
TI  - Religiousness and aggression in adolescents: The mediating roles of self-control
      and compassion.
AB  - Although people have used religion to justify aggression, evidence suggests that
      greater religiousness corresponds with less aggression. We explored two
      explanations for the religion-aggression link. First, most major religions teach
      self-control (e.g., delaying gratification, resisting temptation), which
      diminishes aggression. Second, most major religions emphasize compassionate
      beliefs and behavior (i.e., perspective taking, forgiveness, a broader love of
      humanity) that are incompatible with aggression. We tested whether self-control
      and compassion mediated the relationship between religion and aggression (direct
      and indirect) in a longitudinal study of 1,040 adolescents in the United States.
      Structural equation analyses revealed that self-control and compassion together
      completely mediated the religion-aggression relationship for both types of
      aggression.

PMID- 26205758
TI  - Comparison of Health Care Experience and Access Between Young and Older Adults in
      11 High-Income Countries.
AB  - PURPOSE: Young adults (18-24 years) frequently report poorer health care access
      and experience than older adults. We aimed to investigate how differences between
      young and older adults vary across 11 high-income countries. METHODS: A total of
      20,045 participants from 11 high-income countries (i.e., Australia, Canada,
      France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland,
      United Kingdom, United States) participating in the Commonwealth Fund 2013
      International Health Policy Survey. We compared young adults (18-24 years) with
      older adults (25-34; 35-49; 50-64; 65+ years) on three aspects of health care:
      overall satisfaction, cost barriers to access, and four indicators of
      consultation quality relating to adequate information, time, involvement, and
      explanation. RESULTS: Across all participants, young adults reported
      significantly worse overall satisfaction (63.6% vs. 70.3%; p < .001) and more
      frequent cost barriers (21.3% vs. 15.2%; p < .001) than older adults. Country
      level analyses showed that young adults reported lower overall satisfaction than
      older adults in five of 11 countries (Australia, Canada, Norway, Switzerland,
      United States) and more frequent cost barriers in six of 11 countries (Canada,
      France, Germany, Switzerland, Norway, United States). In five countries
      (Australia, Canada, France, Norway, Switzerland), most patient experience
      indicators were less positive among young adults than those among older adults.
      In three countries (Netherlands, New Zealand, United Kingdom), there was no
      significant difference between young and older adults on any indicator.
      CONCLUSIONS: Associations between age and health care access/experience varied
      markedly between countries, suggesting that poor access and experience among
      young adults is not inevitable and may be amenable to policy/practice
      interventions.

PMID- 26205759
TI  - Tacrolimus combined with corticosteroids versus Modified Ponticelli regimen in
      treatment of idiopathic membranous nephropathy: Randomized control trial.
AB  - AIM: There have been very few studies comparing cyclophosphamide (CTX) and
      calcineurin inhibitor based regimens in the management of non-immunosuppressive
      symptomatic therapy (NIST) resistant idiopathic membranous nephropathy (IMN). The
      present study was aimed at comparing the efficacy and safety of tacrolimus
      (TAC)/steroids with cyclical CTX/steroids (Modified Ponticelli regimen (MPR)) in
      patients with IMN. METHODS: Idiopathic membranous nephropathy patients (n = 70)
      with persistent nephrotic syndrome after at least 6 months of antiproteinuric
      therapy or with complications of nephrotic syndrome were equally randomized to
      receive TAC with oral prednisolone (TAC*) or MPR. Antibodies against m-type
      phospholipase A2 receptor (PLA2R Ab) were tested for at baseline and, at 6 and 12
      months after the start of therapy. The primary end point was achievement of
      remission and secondary objectives were adverse effects and estimated glomerular
      filtration rate in both the study groups. RESULTS: Intention-to-treat analysis
      showed that remissions at the end of 6 (74% with TAC* vs. 60% with MPR; P = 0.30)
      and 12 months (71% with TAC* vs. 77% with MPR; P = 0.78) were comparable. PLA2R
      Ab titres at 6/12 months correlated with urine protein (r 0.54/0.58) and serum
      albumin (r -0.49/-0.53) at the end of therapy. Patients on CTX had a
      significantly higher risk of amenorrhea and while those on TAC had a greater risk
      of reversible nephrotoxicity. CONCLUSION: In NIST refractory IMN, both TAC* and
      MPR are comparable, but with different adverse effect profile. PLA2 R Ab has a
      very good association with proteinuria, and should be regularly monitored on
      clinical follow-up.

PMID- 26205760
TI  - Feasibility of diffusion-weighted magnetic resonance imaging in patients with
      juvenile idiopathic arthritis on 1.0-T open-bore MRI.
AB  - OBJECTIVE: To evaluate the feasibility of non-invasive diffusion-weighted imaging
      (DWI) of the knee of children with juvenile idiopathic arthritis (JIA) and,
      further, to analyze the apparent diffusion coefficient (ADC) levels to
      distinguish synovium from effusion. MATERIALS AND METHODS: Standard magnetic
      resonance imaging of the knee including post-contrast imaging was obtained in
      eight patients (mean age, 12 years 8 months, five females) using an open-bore
      magnetic resonance imaging system (1.0 T). In addition, axially acquired echo
      planar DWI datasets (b-values 0, 50, and 600) were prospectively obtained and the
      diffusion images were post-processed into ADC50-600 maps. Two independent
      observers selected a region of interest (ROI) for both synovium and effusion
      using aligned post-contrast images as landmarks. Mann-Whitney U test was
      performed to compare ADC synovium and ADC effusion. RESULTS: DWI was successfully
      obtained in all patients. When data of both observers was combined, ADC synovium
      was lower than ADC effusion in the ROI in seven out of eight patients (median,
      1.92 * 10(-3) mm(2)/s vs. 2.40 * 10(-3) mm(2)/s, p = 0.006, respectively).
      Similar results were obtained when the two observers were analyzed separately
      (observer 1: p = 0.006, observer 2: p = 0.04). CONCLUSIONS: In this pilot study,
      on a patient-friendly 1.0-T open-bore MRI, we demonstrated that DWI may
      potentially be a feasible non-invasive imaging technique in children with JIA. We
      could differentiate synovium from effusion in seven out of eight patients based
      on the ADC of synovium and effusion. However, to select synovium and effusion on
      DWI, post-contrast images were still a necessity.

PMID- 26205761
TI  - Predictive value of semi-quantitative MRI-based scoring systems for future knee
      replacement: data from the osteoarthritis initiative.
AB  - PURPOSE: To evaluate, in a confirmatory fashion, whether baseline and change from
      baseline to 24-month follow-up in cartilage damage, bone marrow lesions and
      meniscal damage are predictors of knee replacement (KR) in subjects with a high
      risk of osteoarthritis (OA), independent of the level of physical activity,
      symptom severity and radiographic abnormalities. METHODS: Data from the
      Osteoarthritis Initiative's (OAI) baseline and 24-month follow-up knee MRIs of
      115 patients (age range: 45-78 years; 48 % female; BMI: 20.9-48.7) were analyzed.
      Cartilage, bone marrow and menisci were semi-quantitatively scored according to
      the Whole-Organ Magnetic Resonance Imaging Score (WORMS) and Boston-Leeds
      Osteoarthritis Knee Score (BLOKS) systems in all compartments. Baseline and 24
      month interval changes in structural tissue damage assessed by BLOKS and WORMS
      were used as predictors of KR independent of clinical and radiographic parameters
      using Cox hazard analysis. Adjustments were performed for age, gender, BMI and
      physical activity (Physical Activity Scale for the Elderly: PASE), Western
      Ontario and McMaster Questionnaire (WOMAC) total score and radiographic Kellgren
      Lawrence (KL) score. RESULTS: BLOKS and WORMS baseline cartilage scores were
      predictors of KR independent of the PASE, WOMAC and KL score. One score increase
      in the average baseline BLOKS full-thickness cartilage defect score was
      associated with a [hazard ratio (95 % CI)] 13.55 (3.61-50.89) times greater risk
      of KR independent of the PASE, WOMAC and KL score. Net reclassification
      improvements (NRIs) of the additional evaluation of 24-month follow-up MRI scores
      and assessment of changes were not significant for prediction of KR (NRI range: -
      7.23 - 24.8 %). CONCLUSIONS: The BLOKS cartilage score for full-thickness
      cartilage defects had the highest hazard for KR. Follow-up MRI changes in
      structural tissue damage, detected by BLOKS and WORMS cartilage, bone marrow or
      meniscus scores (up to 24 months) had no significant predictive value in addition
      to the baseline MRI.

PMID- 26205763
TI  - Energy expenditure during the group exercise course Bodypump in young healthy
      individuals.
AB  - AIM: The purpose of the present study was to examine the energy expenditure
      during the group resistance training exercise course Bodypump in young healthy
      individuals. METHODS: The study population consisted of 40 men and women (age:
      31.7+/-5.8 years, body mass index [BMI]: 24+/-2.6 kg/m2) that performed three 60
      min sessions of the group resistance training exercise course Bodypump. Free
      living energy expenditure during the course was measured using the portable
      SenseWear armband. Perceived energy expenditure, perception of effort, fatigue
      and pleasure were also measured after the course. RESULTS: Mean energy
      expenditure and intensity during the Bodypump course for all participants were
      250.3+/-67.8 kcal or 4.2 kcal/min and 3.5+/-0.7 METS, respectively.
      Interestingly, perceived energy expenditure for all participants was
      significantly higher by ~67% compared to measured energy expenditure (394.1+/-116
      vs. 250.3+/-67.8 kcal, respectively; P<0.05). Moreover, 85% of all individuals
      reported that the Bodypump course was highly enjoyable. CONCLUSION: Energy
      expenditure during a 60-min Bodypump course appears to be approximately 250 kcal
      and seems to be performed at a moderate intensity (3.5 METS) in young healthy men
      and women. These results could have an impact on the amount of physical activity
      an individual performs as well as the preparation of physical activity programs
      by kinesiologists.

PMID- 26205762
TI  - Characterization of the anatomy of the anterolateral ligament of the knee using
      magnetic resonance imaging.
AB  - OBJECTIVE: The anterolateral ligament (ALL) may limit tibial internal rotation
      and pivot-shift following anterior cruciate ligament reconstruction. Previous
      studies, using magnetic resonance imaging (MRI) to identify this structure, have
      been inconsistent. We aimed to further characterize the anatomy of this ligament
      with reference to previous work. MATERIALS AND METHODS: Institutional Review
      Board approval was gained and a retrospective study of 154 consecutive 1.5-T MRI
      studies was performed by a consultant musculoskeletal radiologist. Cases with a
      lateral compartment or cruciate injury and patients under 16 years were excluded.
      A total of 100 MRIs (98 patients; 63 males: 35 females; mean age, 45.3 years,
      range, 16-85 years) were included in the study. RESULTS: The ALL was visualized
      partially in 94 (94.0%) of the cases and fully with distinct femoral and tibial
      fibers in 57 (57.0%) of the cases. Although the femoral origin was discreet in
      only 57 (57.0%) of cases, the tibial insertion (7.64 +/- 1.26 mm below the joint
      line) and meniscal attachment were demonstrated in all cases where the ligament
      was seen. Where the femoral origin was not seen, a broad expansion of the
      ligament was noted. We identified four types of meniscal attachment (complete,
      central, bipolar, and inferior-only). The thickness of the ALL, at the level of
      the joint-line, was 1.75 +/- 0.57 mm. CONCLUSIONS: The ALL is a consistent
      structure with meniscal and tibial portions identifiable in the majority of MRI
      studies of the uninjured knee. There is an attachment to the lateral meniscus
      with anatomical variation described by our subclassification.

PMID- 26205764
TI  - Deviations of frequency and the mode of vibration of commercially available whole
      body vibration training devices.
AB  - AIM: Research in the field of whole body vibration (WBV) training and the use of
      it in practice might be hindered by the fact that WBV training devices generate
      and transmit frequencies and/or modes of vibration which are different to preset
      adjustments. This research project shall clarify how exact WBV devices apply the
      by manufacturer information promised preset frequency and mode of vibration.
      METHODS: Nine professional devices for WBV training were tested by means of a tri
      axial accelerometer. The accelerations of each device were recorded under
      different settings with a tri-axial accelerometer. Beneath the measurement of
      different combinations of preset frequency and amplitude the repeatability across
      3 successive measurements with the same preset conditions and one measurement
      under loaded condition were carried out. RESULTS: With 3 exceptions (both Board
      3000 & srt medical PRO) we did not find noteworthy divergences between preset and
      actual applied frequencies. In these 3 devices we found divergences near -25%.
      Loading the devices did not affect the applied frequency or mode of vibration.
      There were no important divergences measurable for the applied frequency and mode
      of vibration regarding repeatability. CONCLUSION: The results of our measurements
      cannot be generalized as we only measured one respectively at most two devices of
      one model in terms of a random sample. Based on these results we strongly
      recommend that user in practice and research should analyse their WBV training
      devices regarding applied frequency and mode of vibration.

PMID- 26205765
TI  - Comparison of stretch reflex responses evoked during drop jumping in highly
      skilled atheles versus untrained subjects.
AB  - AIM: The purpose of the study was to describe changes in the excitability of the
      stretch reflex response (SRR) during different drop jumps as a function of
      training background and as an adaptation to a preseason sport-specific resistance
      training program. METHODS: Twelve collegiate field event athletes (discus,
      hammer, javelin, shot put, and weight; 9 males and 3 females) and 12 college-aged
      control subjects performed the following three jumps: (1) countermovement jump
      (CMJ); (2) countermovement drop jump; and (3) bounce-drop jump (BDJ).
      Neuromechanical changes in the performance of drop jumps by athletes were
      measured during the sport-specific resistance training program. Pre-post testing
      of drop jump performance by control subjects was included for comparison. For
      each jump trial, ground reaction forces (GRF), electromyograms (EMG) and
      cinematographic data were collected. RESULTS: There were no training adaptations.
      However, jump heights were greater for the athletes than the controls among the
      different jumps with the jump heights for all subjects being less during the BDJ
      than CMJ and CDJ. In athletes only, there was a differential modulation of the
      SRR from the gastrocnemius muscle with different levels of background muscle
      activity for the CDJ and BDJ. CONCLUSION: There were changes in excitability of
      SRR from the gastrocnemius muscle as a function of training background.
      Interrelated neuromechanical mechanisms to include landing biomechanics,
      intrinsic musculotendinous tissue properties of the ankle, and centrally
      regulated motor commands may underlie the facilitation of the SRR from the
      gastrocnemius muscle in athletes as compared to controls.

PMID- 26205766
TI  - Relationship between cardiorespiratory fitness, habitual physical activity, body
      mass index and premenstrual symptoms in collegiate students.
AB  - AIM: Several factors may be related to premenstrual symptoms (PMS) including
      physical and psychological symptoms and the aim of this study is to investigate
      the relationship between cardiorespiratory fitness (CRF), habitual physical
      activity including exercise and non exercise activity, body mass index (BMI) and
      physical and psychological symptoms of PMS. METHODS: In a cross-sectional survey
      86 young girls (age:18-25 years) who met the study criteria voluntary
      participated in this study. Participants completed Moos Menstrual Distress and
      life style habit questionnaires. CRF was calculated using the Bruce treadmill
      test. Weight and height of participants were recorded for estimating body mass
      index. The Pearson correlation coefficient and multiple regression analysis were
      used for analysis of the data. RESULTS: CRF was significantly negatively
      correlated with physical and psychological symptoms of PMS (P<0.05); exercise
      activity was significantly and negatively correlated with physical and
      psychological symptoms (P<0.05). BMI was significantly and positively correlated
      with physical and psychological symptoms (P<0.05), but non-exercise activity was
      not associated with physical or psychological symptoms of PMS (P>0.05).
      CONCLUSIONS: The higher level of CRF and exercise activity was related to lower
      but higher BMI was related to higher PMS symptoms. CRF was the strongest
      predictor of physical and psychological symptoms of PMS.

PMID- 26205767
TI  - Effects of N-acetylcysteine and L-arginine in the antioxidant system of C2C12
      cells.
AB  - AIM: The aim of this study was to evaluate the effects of N-acetylcysteine or L
      arginine in the antioxidant system of skeletal muscle cells in culture. METHODS:
      We used C2C12 cells which were supplemented or not with N-acetylcysteine or L
      arginine at different time points. Antioxidant enzymes' activities and protein
      expression were evaluated. Additionally, superoxide production by cytochrome c
      reduction method was carried out. RESULTS: It was observed that the
      supplementation with either N-acetylcysteine or L-arginine was capable to acutely
      reduce superoxide production (after 30 and 60 minutes). Surprisingly, N
      acetylcysteine supplementation also induced an increased production of superoxide
      during the period of 24 hours. Moreover, both supplements were capable to improve
      the activity and protein expression of some antioxidants enzymes. CONCLUSION: In
      conclusion, we have found new evidences showing that N-acetylcysteine or L
      arginine supplementation can provide some benefits to the antioxidant system of
      skeletal muscle cells in culture. Further studies have to be carried out to
      evaluate if such benefits could also occur in an in vivo model, with possible
      benefits for athletes' health and performance.

PMID- 26205768
TI  - Quality of life of patients with chronic lymphocytic leukaemia in the
      Netherlands: results of a longitudinal multicentre study.
AB  - PURPOSE: To describe the health-related quality of life (HRQoL) of an unselected
      population of patients with chronic lymphocytic leukaemia (CLL) including
      untreated patients. METHODS: HRQoL was measured by the EORTC QLQ-C30 including
      the CLL16 module, EQ-5D, and VAS in an observational study over multiple years.
      All HRQoL measurements per patient were connected and analysed using area under
      the curve analysis over the entire study duration. The total patient group was
      compared with the general population, and three groups of CLL patients were
      described separately, i.e. patients without any active treatment ("watch and
      wait"), chlorambucil treatment only, and patients with other treatment(s).
      RESULTS: HRQoL in the total group of CLL patients was compromised when compared
      with age- and gender-matched norm scores of the general population. CLL patients
      scored statistically worse on the VAS and utility score of the EQ-5D, all
      functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea,
      sleeping disturbance, appetite loss, and financial difficulties. In untreated
      patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was
      compromised considerably. Patients treated with chlorambucil only scored worse on
      the EORTC QLQ-C30 than patients who were treated with other treatments with
      regard to emotional functioning, cognitive functioning, bruises, uncomfortable
      stomach, and apathy. CONCLUSIONS: CLL patients differ most from the general
      population on role functioning, fatigue, concerns about future health, and having
      not enough energy. Once treatment is indicated, HRQoL becomes considerably
      compromised. This applies to all treatments, including chlorambucil, which is
      considered to be a mild treatment.

PMID- 26205769
TI  - Burden of caregivers of adult patients with schizophrenia in a predominantly
      African ancestry population.
AB  - PURPOSE: There is relative inattention to caregiving burden in black populations
      in developing economies. This study seeks to assess the level of perceived burden
      and social determinants of burden of care in caregivers of adult patients with
      schizophrenia. METHODS: In this cross-sectional study, 115 dyads of patients with
      schizophrenia caregivers attending public mental health clinics were
      consecutively recruited. Burden of care was evaluated using the 22-item Zarit
      Burden Scale (maximum score, 88). Multiple linear regression model explored
      factors associated with caregiver burden. RESULTS: Caregivers were predominantly
      females (75.7 %) and were on average 50.8 +/- 15.0 years. Most patients with
      schizophrenia were males (65.2 %) and were on average 43.6 +/- 17.2 years old.
      Caregivers showed on average, mild-to-moderate burden (score, 30.0 +/- 14.7;
      median, 28.0). There was tendency for caregivers of patients who were parents or
      spouses to have higher levels of burden. In multivariable analyses, higher burden
      of caregiving was associated with patient's inability to perform self-care (B +/-
      SE, 5.12 +/- 1.40; p = 0.0001), closer kinship and higher numbers of psychotic
      episodes in previous year. The length of caregiving relationship was inversely
      related. CONCLUSIONS: Poorer functioning and demographic factors were important
      determinants of caregiver burden. Community mental health services should include
      self-care interventions in rehabilitation programs in Jamaica.

PMID- 26205770
TI  - Elevated Endomyocardial Biopsy Macrophage-Related Markers in Intractable
      Myocardial Diseases.
AB  - Tissue macrophages can be activated by endogenous danger signals released from
      cells that are stressed or injured, leading to infiltration of inflammatory
      macrophages and neutrophils. We postulated that macrophage-related markers might
      be closely associated with the existence of endogenous danger signals, reflecting
      ongoing tissue injury in the absence of foreign substances. This study was
      designed to assess the ability of macrophage-related markers in endomyocardial
      biopsies to predict ongoing cardiac injury in non-inflammatory myocardial
      diseases. We examined levels of macrophage-related markers (CD68, CD163, CD45) in
      endomyocardial biopsies from patients (n = 86) with various myocardial diseases
      by quantitative reverse transcription-polymerase chain reaction (n = 78) and
      immunohistochemistry (n = 56). Thirty-three patients without inflammatory cardiac
      disease such as myocarditis and sarcoidosis were classified as "improved" or "non
      improved" defined as a 10% increase in left ventricular ejection fraction by
      echocardiograph and a value greater than 30% at the time of follow-up. All
      macrophage-related (MacR) markers levels were not higher in non-improved dilated
      cardiomyopathy (DCM) patients than improved patients. However, patients with
      cardiac amyloidosis, cardiac Fabry disease, mitochondrial cardiomyopathy, and
      biventricular arrhythmogenic right ventricular cardiomyopathy (ARVC), which were
      categorized as "non-improvement diseases," had elevated macrophage-related
      markers compared to improved patients. Macrophage-related markers levels were
      increased in endomyocardial biopsy samples of patients with intractable
      myocardial diseases such as amyloidosis, mitochondrial disease, Fabry disease,
      and biventricular ARVC.

PMID- 26205771
TI  - In vitro biological action of aqueous extract from roots of Physalis angulata
      against Leishmania (Leishmania) amazonensis.
AB  - BACKGROUND: Leishmaniasis is an infectious disease caused by various species of
      the protozoan parasites of the Leishmania genus and transmitted by phlebotomine
      sandflies. The protozoa multiply in phagocytic cells, mainly macrophages, which
      play an important role defending the organism from pathogens. The most effective
      treatment for leishmaniasis is the chemotherapy and besides the high cost, these
      drugs are toxic and require a long period of treatment. Currently, some herbal
      products are considered an important alternative source of a new leishmanicidal
      agent, which includes the plant Physalis angulata, . We evaluated effects of an
      aqueous extract from roots of Physalis angulata (AEPa) on Leishmania
      proliferation, morphology and also determined whether physalins were present in
      the extract contributing to the knowledge of its pharmacological efficacy.
      METHODS: Morphological alterations were determined by light microscopy,
      transmission and scanning electron microscopy. Host cell viability was evaluated
      by MTT, and propidium iodide. AEPa were submitted in full HRESITOF analysis.
      RESULTS: AEPa promoted a dose-dependent reduction on promastigotes (IC50 = 39.5
      MUg/mL +/- 5.1) and amastigotes (IC50 = 43.4 MUg/mL +/- 10.1) growth. This growth
      inhibition was associated with several morphological alterations observed in
      promastigote forms. No cytotoxic effect in mammalian cells was detected (IC50 >
      4000 MUg/mL). Furthemore, the presence of physalins A, B, D, E, F, G and H were
      described, for the first time, in the P. angulata root. CONCLUSIONS: Results
      demonstrate that AEPa effectively promotes antileishmanial activity with several
      important morphological alterations and has no cytotoxic effects on host cells.

PMID- 26205772
TI  - Development and validation of a model of motor competence in children and
      adolescents.
AB  - OBJECTIVES: This study was aimed at developing a quantitative model to evaluate
      motor competence (MC) in children and adolescents, to be applicable in research,
      education, and clinical contexts. DESIGN: Cross-sectional. METHODS: A total of
      584 children (boys n=300) with ages between 6 and 14 years were assessed using
      nine well known quantitative motor tasks, divided into three major components
      (stability, locomotor and manipulative). Structural equation modelling through
      EQS 6.1 was used to find the best model for representing the structural and
      measurement validity of MC. RESULTS: The final MC model was composed by three
      latent factors closely related with each other. Each factor was best represented
      by two of the initial three motor tasks chosen. The model was shown to give a
      very good overall fit (chi(2)=12.04, p=.061; NFI=.982; CFI=.991; RMSEA=.059).
      CONCLUSIONS: MC can be parsimoniously represented by six quantitative motor
      tasks, grouped into three interrelated factors. The developed model was shown to
      be robust when applied to different samples, demonstrating a good structural and
      measurement reliability. The use of a quantitative protocol with few, simple to
      administer and well known, motor tasks, is an important advantage of this model,
      since it can be used in several contexts with different objectives. We find it
      especially beneficial for physical educations teachers who have to regularly
      assess their students.

PMID- 26205773
TI  - The impact of injury definition on injury surveillance in novice runners.
AB  - OBJECTIVES: Despite several consensus statements, different injury definitions
      are used in the literature. This study aimed to identify the impact of different
      injury definitions on the nature and incidence of complaints captured during a
      short-term running program for novice runners. DESIGN: Prospective cohort study.
      METHODS: 1696 participants completed weekly diaries on running exposure and
      musculoskeletal complaints during a 6-week running program. These data were used
      to compare six different injury definitions (presence of running-related pain,
      training-reduction, time-loss of one day or one week). Injuries were registered
      under these different definitions. Consequently incidence and the nature of
      complaints were compared between definitions. RESULTS: The different injury
      definitions resulted in incidences that varied between 7.5% and 58.0%, or 18.7
      and 239.6 injuries per 1000h of running. The median duration of injury complaints
      was 4-7 days for injuries registered under a 'day definition', while complaints
      registered under a 'week definition' lasted 20-22 days. For running-related pain
      injuries the median of the maximum amount of pain was 3.0. In training-reduction
      and time-loss injuries these median values were scored between 5.0 and 7.0. No
      significant differences in anatomical locations between injuries that were
      registered under a 'day definition' or a 'week definition' were found. Injuries
      registered under a time-loss definition were located relatively more often at the
      knee, while complaints at the pelvis/sacrum/buttock were captured more often
      under a running-related pain definition. CONCLUSIONS: Injury definitions largely
      impact injury incidence. Location of injury is also affected by choice of injury
      definition. This stressed the need for standardized injury registration methods.

PMID- 26205774
TI  - Predictors and effects of patellofemoral pain following hamstring-tendon ACL
      reconstruction.
AB  - OBJECTIVES: Patellofemoral pain is a frequent and troublesome complication
      following anterior cruciate ligament reconstruction (ACLR), irrespective of graft
      source. Yet, little is known about the factors associated with patellofemoral
      pain following hamstring-tendon ACLR. DESIGN: Retrospective analysis of potential
      patellofemoral pain predictors, and cross-sectional analysis of possible
      patellofemoral pain consequences. METHODS: Potential predictors (pre-injury
      patellofemoral pain and activity level, concomitant patellofemoral cartilage
      damage and meniscectomy, age, sex, and surgical delay) and consequences (hopping
      performance, quality of life, kinesiophobia, and return to sport rates and
      attitudes) of patellofemoral pain 12 months following hamstring-tendon ACLR were
      assessed in 110 participants using univariate and multivariate analyses. RESULTS:
      Thirty-three participants (30%) had patellofemoral pain at 12 months post-ACLR.
      Older age at the time of ACLR was the only predictor of post-operative
      patellofemoral pain. Following ACLR, those with patellofemoral pain had a higher
      body mass index, and worse physical performance, quality of life, kinesiophobia
      and return to sport attitudes. Patellofemoral pain has a significant burden on
      individuals 12 months following hamstring-tendon ACLR. CONCLUSIONS: Clinicians
      need to be cognisant of patellofemoral pain, particularly in older individuals
      and those with a higher body mass index. The importance of considering
      psychological factors that are not typically addressed during ACLR
      rehabilitation, such as kinesiophobia, quality of life and return to sport
      attitudes is emphasised.

PMID- 26205775
TI  - PACE: A group randomised controlled trial to increase children's break-time
      playground physical activity.
AB  - OBJECTIVES: To assess the effect of a school playground intervention on the
      physical activity levels of primary/elementary aged children. DESIGN: Two-arm
      parallel group randomized controlled trial. METHODS: In 2011, children aged 4-13
      years from thirteen primary/elementary schools (in Illawarra, New South Wales,
      Australia) were invited to participate in the study. School recruitment was based
      on existing policies, equipment and willingness to participate. Participating
      schools were randomly allocated to the intervention or control using the 'hat and
      draw' method. The intervention was delivered over four months. Intervention
      schools introduced policy changes and portable equipment to break-time after
      baseline measures were collected. The primary outcome was the proportion of break
      time spent in Moderate to Vigorous Physical Activity (MVPA) assessed by the
      System for Observing Playground Activity in Youth (SOPLAY). The analysis involved
      linear mixed models adjusting for the clustering effect of schools. The study is
      registered with the Australian New Zealand Clinical Trials Registry
      (ACTRN12614001128684). RESULTS: Four schools (two intervention and two control)
      met the inclusion criteria (1582 children: 790 males; 267 controls, total of 792
      females; 248 controls). Students from the intervention schools had a greater
      increase at follow-up in the proportion of break-time in MVPA; (adjusted
      difference=12.5 percentage points, 95% CI [-13.0%, 38.0%]; P=0.17; r=0.6)
      compared to the controls. MVPA at recess significantly increased (adjusted
      difference=18.0 percentage points, 95% CI [6.9%, 29.1%]; P=0.02; effect
      size=0.7). There were no significant increases in MVPA when examining overall
      break times. Results were greater for girls compared to boys. CONCLUSIONS: Making
      environmental and policy changes are promising strategies for promoting health
      enhancing physical activity during school break-time.

PMID- 26205776
TI  - Medicare's procedures for screening doctors are faulty, report says.

PMID- 26205777
TI  - Ultrasound analysis of mental artery flow in elderly patients: a case-control
      study.
AB  - OBJECTIVES: Mental artery flow decreases with age and may have an aetiological
      role in alveolar ridge atrophy. The aim of this study was to identify factors
      associated with alterations of mental artery flow, assessed by ultrasonography.
      METHODS: This case-control study was conducted on elderly patients (aged above 60
      years) at the beginning of dental treatment. Intraoral B-mode Doppler
      ultrasonography was used to assess mental artery flow. The cases were defined as
      patients with a weak/absent ultrasound signal, whereas the controls presented a
      strong ultrasound signal. Demographics and radiographic findings (low bone
      mineral density on dual-energy X-ray absorptiometry and mandibular cortical index
      on panoramic radiographs) were analysed as risk factors for weak/absent
      ultrasound signal and were calculated as adjusted odds ratios (AORs) with 95%
      confidence intervals (CIs) using conditional logistic regression. In addition,
      the Student's t-test was used to compare the mean alveolar bone height of the
      analysed groups. A p-value <0.05 was considered statistically significant.
      RESULTS: A total of 30 ultrasound examinations (12 cases and 18 controls) were
      analysed. A weak/absent mental artery pulse strength was significantly associated
      with edentulism (AOR = 3.67; 95% CI = 0.86-15.63; p = 0.046). In addition, there
      was a significant difference in alveolar bone height between edentulous cases and
      controls (p = 0.036). CONCLUSIONS: Within the limitations of this study, the
      present results indicate that edentulism is associated with diminished mental
      artery flow, which, in turn, affects alveolar bone height.

PMID- 26205778
TI  - BONLAC: A combinatorial proteomic technique to measure stimulus-induced
      translational profiles in brain slices.
AB  - Stimulus-triggered protein synthesis is critical for brain health and function.
      However, due to technical hurdles, de novo neuronal translation is predominantly
      studied in cultured cells, whereas electrophysiological and circuit analyses
      often are performed in brain slices. The different properties of these two
      experimental systems create an information gap about stimulus-induced alterations
      in the expression of new proteins in mature circuits. To address this, we adapted
      two existing techniques, BONCAT and SILAC, to a combined proteomic technique,
      BONLAC, for use in acute adult hippocampal slices. Using BDNF-induced protein
      synthesis as a proof of concept, we found alterations in expression of proteins
      involved in neurotransmission, trafficking, and cation binding that differed from
      those found in a similar screen in cultured neurons. Our results indicate
      important differences between cultured neurons and slices, and suggest that
      BONLAC could be used to dissect proteomic changes underlying synaptic events in
      adult circuits. This article is part of the Special Issue entitled 'Synaptopathy-
      from Biology to Therapy'.

PMID- 26205779
TI  - PARP is activated in human asthma and its inhibition by olaparib blocks house
      dust mite-induced disease in mice.
AB  - Our laboratory established a role for poly(ADP-ribose)polymerase (PARP) in
      asthma. To increase the clinical significance of our studies, it is imperative to
      demonstrate that PARP is actually activated in human asthma, to examine whether a
      PARP inhibitor approved for human testing such as olaparib blocks already
      established chronic asthma traits in response to house dust mite (HDM), a true
      human allergen, in mice and to examine whether the drug modulates human cluster
      of differentiation type 4 (CD4(+)) T-cell function. To conduct the study, human
      lung specimens and peripheral blood mononuclear cells (PBMCs) and a HDM-based
      mouse asthma model were used. Our results show that PARP is activated in PBMCs
      and lung tissues of asthmatics. PARP inhibition by olaparib or gene knockout
      blocked established asthma-like traits in mice chronically exposed to HDM
      including airway eosinophilia and hyper-responsiveness. These effects were linked
      to a marked reduction in T helper 2 (Th2) cytokine production without a prominent
      effect on interferon (IFN)-gamma or interleukin (IL)-10. PARP inhibition
      prevented HDM-induced increase in overall cellularity, weight and CD4(+) T-cell
      population in spleens of treated mice whereas it increased the T-regulatory cell
      population. In CD3/CD28-stimulated human CD4 (+)T-cells, olaparib treatment
      reduced Th2 cytokine production potentially by modulating GATA binding protein-3
      (gata-3)/IL-4 expression while moderately affecting T-cell proliferation. PARP
      inhibition inconsistently increased IL-17 in HDM-exposed mice and CD3/CD28
      stimulated CD4(+) T cells without a concomitant increase in factors that can be
      influenced by IL-17. In the present study, we provide evidence for the first time
      that PARP-1 is activated in human asthma and that its inhibition is effective in
      blocking established asthma in mice.

PMID- 26205780
TI  - Identifying novel hypoxia-associated markers of chemoresistance in ovarian
      cancer.
AB  - BACKGROUND: Ovarian cancer is associated with poor long-term survival due to late
      diagnosis and development of chemoresistance. Tumour hypoxia is associated with
      many features of tumour aggressiveness including increased cellular
      proliferation, inhibition of apoptosis, increased invasion and metastasis, and
      chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1alpha.
      While HIF-1alpha has been associated with platinum resistance in a variety of
      cancers, including ovarian, relatively little is known about the importance of
      the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer
      which cause chemoresistance as a result of hypoxia are poorly understood. This
      study aimed to firstly investigate the effect of hypoxia duration on resistance
      to cisplatin in an ovarian cancer chemoresistance cell line model and to identify
      genes whose expression was associated with hypoxia-induced chemoresistance.
      METHODS: Cisplatin-sensitive (A2780) and cisplatin-resistant (A2780cis) ovarian
      cancer cell lines were exposed to various combinations of hypoxia and/or
      chemotherapeutic drugs as part of a 'hypoxia matrix' designed to cover clinically
      relevant scenarios in terms of tumour hypoxia. Response to cisplatin was measured
      by the MTT assay. RNA was extracted from cells treated as part of the hypoxia
      matrix and interrogated on Affymetrix Human Gene ST 1.0 arrays. Differential gene
      expression analysis was performed for cells exposed to hypoxia and/or cisplatin.
      From this, four potential markers of chemoresistance were selected for evaluation
      in a cohort of ovarian tumour samples by RT-PCR. RESULTS: Hypoxia increased
      resistance to cisplatin in A2780 and A2780cis cells. A plethora of genes were
      differentially expressed in cells exposed to hypoxia and cisplatin which could be
      associated with chemoresistance. In ovarian tumour samples, we found trends for
      upregulation of ANGPTL4 in partial responders and down-regulation in non
      responders compared with responders to chemotherapy; down-regulation of HER3 in
      partial and non-responders compared to responders; and down-regulation of HIF
      1alpha in non-responders compared with responders. CONCLUSION: This study has
      further characterized the relationship between hypoxia and chemoresistance in an
      ovarian cancer model. We have also identified many potential biomarkers of
      hypoxia and platinum resistance and provided an initial validation of a subset of
      these markers in ovarian cancer tissues.

PMID- 26205781
TI  - Nicotine attenuates the effect of HIV-1 proteins on the neural circuits of
      working and contextual memories.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-1-associated neurocognitive
      disorders (HAND) are characterized by synaptic damage and neuronal loss in the
      brain. Excessive glutamatergic transmission and loss of cholinergic neurons are
      the major indicators of HAND. Nicotine acts as a cholinergic channel modulator,
      and its cognitive-enhancing effect in neurodegenerative and cognitive disorders
      has been documented. However, it is unclear whether nicotine has any positive
      effect on memory and synaptic plasticity formation in HAND. METHODS: We
      investigated the effects of nicotine on synaptic plasticity and hippocampus
      prefrontal cortex (PFC)-amygdala-dependent memory formation in the HIV-1
      transgenic (Tg) and F344 control rats. RESULTS: Chronic nicotine treatment (0.4
      mg/kg nicotine, base, subcutaneously) significantly attenuated the cognitive
      deficits in the HIV-1Tg rats in both the spatial and contextual fear memories but
      impaired the contextual learning memory in the F344 rats. To determine the role
      of nicotine in the synaptic dysfunction caused by HIV-1 proteins, we analyzed the
      expression of key representative genes related to synaptic plasticity in the
      hippocampus, PFC, and amygdala of the HIV-1Tg and F344 rats using a custom
      designed qRT-PCR array. The HIV-1 proteins significantly altered the glutamate
      receptor-mediated intracellular calcium cascade and its downstream signaling
      cascade in a brain region-specific manner. Further, chronic nicotine treatment
      reversed the effect of HIV-1 proteins on the expression of genes involved in
      synaptic plasticity in the three brain regions. The effects of nicotine differed
      significantly in the HIV-1Tg and F344 rats. CONCLUSIONS: Our findings indicate
      that nicotine can attenuate the effect of HIV viral proteins on cognitive
      function and produce a brain region- and strain-specific effect on the
      intracellular signaling cascades involved in synaptic plasticity and memory
      formation.

PMID- 26205787
TI  - Methyl-CpG-Binding Protein (MBD) Family: Epigenomic Read-Outs Functions and Roles
      in Tumorigenesis and Psychiatric Diseases.
AB  - Epigenetics is the study of the heritable changes on gene expression that are
      responsible for the regulation of development and that have an impact on several
      diseases. However, it is of equal importance to understand how epigenetic
      machinery works. DNA methylation is the most studied epigenetic mark and is
      generally associated with the regulation of gene expression through the
      repression of promoter activity and by affecting genome stability. Therefore, the
      ability of the cell to interpret correct methylation marks and/or the correct
      interpretation of methylation plays a role in many diseases. The major family of
      proteins that bind methylated DNA is the methyl-CpG binding domain proteins, or
      the MBDs. Here, we discuss the structure that makes these proteins a family, the
      main functions and interactions of all protein family members and their role in
      human disease such as psychiatric disorders and cancer.

PMID- 26205786
TI  - Abundant copy-number loss of CYCLOPS and STOP genes in gastric adenocarcinoma.
AB  - BACKGROUND: Gastric cancer, a leading cause of cancer death worldwide, has been
      little studied compared with other cancers that impose similar health burdens.
      Our goal is to assess genomic copy-number loss and the possible functional
      consequences and therapeutic implications thereof across a large series of
      gastric adenocarcinomas. METHODS: We used high-density single-nucleotide
      polymorphism microarrays to determine patterns of copy-number loss and allelic
      imbalance in 74 gastric adenocarcinomas. We investigated whether suppressor of
      tumorigenesis and/or proliferation (STOP) genes are associated with genomic copy
      number loss. We also analyzed the extent to which copy-number loss affects Copy
      number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS)
      genes-genes that may be attractive targets for therapeutic inhibition when
      partially deleted. RESULTS: The proportion of the genome subject to copy-number
      loss varies considerably from tumor to tumor, with a median of 5.5 %, and a mean
      of 12 % (range 0-58.5 %). On average, 91 STOP genes were subject to copy-number
      loss per tumor (median 35, range 0-452), and STOP genes tended to have lower copy
      number compared with the rest of the genes. Furthermore, on average, 1.6 CYCLOPS
      genes per tumor were both subject to copy-number loss and downregulated, and 51.4
      % of the tumors had at least one such gene. CONCLUSIONS: The enrichment of STOP
      genes in regions of copy-number loss indicates that their deletion may contribute
      to gastric carcinogenesis. Furthermore, the presence of several deleted and
      downregulated CYCLOPS genes in some tumors suggests potential therapeutic targets
      in these tumors.

PMID- 26205788
TI  - Oxidation and degradation of graphitic materials by naphthalene-degrading
      bacteria.
AB  - Nowadays, biologically oxidizing graphitic materials is of great importance for
      practical applications as an eco-friendly and low-cost method. In this work, a
      bacterial strain is isolated from the contaminated soil in a graphite mine and
      its ability to oxidize graphite, graphene oxide (GO) and reduced graphene oxide
      (RGO) is confirmed. After being cultivated with bacteria, graphite is
      inhomogeneously oxidized, and moreover oxidized sheets exfoliated from graphite
      are detected in the medium. RGO shows a higher degree of oxidation compared to
      graphite owing to more original defects, while GO breaks into small pieces and
      becomes full of holes. Both the holes in GO and the exfoliated sheets from
      graphite caused by bacteria have a size of below 1 MUm, in agreement with the
      size of bacterial cells. Besides, the preliminary mechanism of the bacterial
      oxidation is explored, suggesting that the contact between bacterial cells and
      materials promotes the oxidation of graphitic materials. The ability of
      naphthalene-degrading bacteria to oxidize and degrade the graphitic materials
      shows the potential for producing GO in an eco-friendly way and degrading carbon
      nanomaterials in the environment. 

PMID- 26205789
TI  - Expression analysis of human adipose-derived stem cells during in vitro
      differentiation to an adipocyte lineage.
AB  - BACKGROUND: Adipose tissue-derived stromal stem cells (ASCs) represent a
      promising regenerative resource for soft tissue reconstruction. Although
      autologous grafting of whole fat has long been practiced, a major clinical
      limitation of this technique is inconsistent long-term graft retention. To
      understand the changes in cell function during the transition of ASCs into fully
      mature fat cells, we compared the transcriptome profiles of cultured
      undifferentiated human primary ASCs under conditions leading to acquisition of a
      mature adipocyte phenotype. METHODS: Microarray analysis was performed on total
      RNA extracted from separate ACS isolates of six human adult females before and
      after 7 days (7 days: early stage) and 21 days (21 days: late stage) of adipocyte
      differentiation in vitro. Differential gene expression profiles were determined
      using Partek Genomics Suite Version 6.4 for analysis of variance (ANOVA) based on
      time in culture. We also performed unsupervised hierarchical clustering to test
      for gene expression patterns among the three cell populations. Ingenuity Pathway
      Analysis was used to determine biologically significant networks and canonical
      pathways relevant to adipogenesis. RESULTS: Cells at each stage showed remarkable
      intra-group consistency of expression profiles while abundant differences were
      detected across stages and groups. More than 14,000 transcripts were
      significantly altered during differentiation while ~6000 transcripts were
      affected between 7 days and 21 days cultures. Setting a cutoff of +/-two-fold
      change, 1350 transcripts were elevated while 2929 genes were significantly
      decreased by 7 days. Comparison of early and late stage cultures revealed
      increased expression of 1107 transcripts while 606 genes showed significantly
      reduced expression. In addition to confirming differential expression of known
      markers of adipogenesis (e.g., FABP4, ADIPOQ, PLIN4), multiple genes and
      signaling pathways not previously known to be involved in regulating adipogenesis
      were identified (e.g. POSTN, PPP1R1A, FGF11) as potential novel mediators of
      adipogenesis. Quantitative RT-PCR validated the microarray results. CONCLUSIONS:
      ASC maturation into an adipocyte phenotype proceeds from a gene expression
      program that involves thousands of genes. This is the first study to compare mRNA
      expression profiles during early and late stage adipogenesis using cultured human
      primary ASCs from multiple patients.

PMID- 26205791
TI  - Peptide Backbone Composition and Protease Susceptibility: Impact of Modification
      Type, Position, and Tandem Substitution.
AB  - The clinical utility of peptides is limited by their rapid degradation by
      endogenous proteases. Modification of the peptide backbone can generate
      functional analogues with enhanced proteolytic stability. Existing principles for
      the design of such oligomers have focused primarily on effective structural
      mimicry. A more robust strategy would incorporate a rational approach for
      engineering maximal proteolytic stability with minimal unnatural residue content.
      We report here the systematic comparison of the proteolytic resistance imparted
      by four backbone modifications commonly employed in the design of protease-stable
      analogues of peptides with complex folding patterns. The degree of protection was
      quantified as a function of modification type, position, and tandem substitution
      in the context of a long, unstructured host sequence and a canonical serine
      protease. These results promise to inform ongoing work to develop biostable
      mimics of increasingly complex peptides and proteins. 

PMID- 26205790
TI  - MEG3 long noncoding RNA regulates the TGF-beta pathway genes through formation of
      RNA-DNA triplex structures.
AB  - Long noncoding RNAs (lncRNAs) regulate gene expression by association with
      chromatin, but how they target chromatin remains poorly understood. We have used
      chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify
      276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one
      of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which
      lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target
      genes, including the TGF-beta pathway genes. Genome-wide mapping of MEG3 binding
      sites reveals that MEG3 modulates the activity of TGF-beta genes by binding to
      distal regulatory elements. MEG3 binding sites have GA-rich sequences, which
      guide MEG3 to the chromatin through RNA-DNA triplex formation. We have found that
      RNA-DNA triplex structures are widespread and are present over the MEG3 binding
      sites associated with the TGF-beta pathway genes. Our findings suggest that RNA
      DNA triplex formation could be a general characteristic of target gene
      recognition by the chromatin-interacting lncRNAs. 

PMID- 26205792
TI  - The effect of socioeconomic status on health-care delay and treatment of
      esophageal cancer.
AB  - BACKGROUND: Socioeconomic status (SES) has been focused on as a key determinant
      of the incidence of cancer, cancer stage at diagnosis as well as treatment
      choices in western countries. However, to the authors' knowledge, little work has
      been done concerning the relationship of SES and esophageal cancer in China.
      METHODS: Patients diagnosed with primary esophageal cancer from January to
      December 2007 in Qilu hospital were included. Socioeconomic status was determined
      by a questionnaire including religion, years of schooling and high education,
      place of residence, occupation, annual household income, and insurance. RESULTS:
      A total of 238 cases were collected in this study. Linear-by-linear association
      testing revealed that health-care delay was significantly associated with SES (P
      = 0.009). Multivariable logistic regression analysis revealed that increased
      health-care delay (>2 months) was more frequently observed in patients with lower
      SES (OR 2.271; 95% CI 1.069-4.853). Patients diagnosed at TNM I and II were more
      frequently in higher SES groups (P = 0.017). The association test was
      statistically significant for undergoing surgical resection only (P = 0.015) and
      chemotherapy (P = 0.015). Multivariable logistic regression analysis revealed
      that surgical resection only was less performed in higher SES group compared with
      lower SES group (OR 0.372; 95% CI 0.188-0.734). For chemotherapy, higher SES
      patients had a three-fold higher likelihood compared with lower SES group (OR
      3.042; 95% CI 1.335-6.928). CONCLUSION: Socioeconomic status was found to be
      associated with health-care delay, tumor stage and treatment modalities in
      esophageal cancer.

PMID- 26205793
TI  - Low concentrations of doxycycline attenuates FasL-induced apoptosis in HeLa
      cells.
AB  - BACKGROUND: Doxycycline (DC) has been shown to possess non-antibiotic properties
      including Fas/Fas Ligand (FasL)-mediated apoptosis against several tumor types in
      the concentration range of 10-40 ug/mL. However, the effect of DC in apoptotic
      signaling at much low concentrations was not studied. METHODS: The present study
      investigated the attenuation effect of low dose of DC on FasL-induced apoptosis
      in HeLa cell by the methods of MTT assay, fluorescence microscopy, DNA
      fragmentation, flow cytometry analysis, and western blotting. RESULTS AND
      CONCLUSION: In the present findings we showed that low concentration of DC (<2.0
      ug/mL) exhibited protective effects against FasL-induced apoptosis in HeLa cells.
      FasL treatment to HeLa cells resulted in a concentration-dependent induction of
      cell death, and treatment with low concentrations of DC (0.1-2 ug/mL)
      significantly (p < 0.001) attenuated the FasL-induced cell death as measured by 3
      (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Further,
      the FasL-induced apoptotic features in HeLa cells, such as morphological changes,
      DNA fragmentation and cell cycle arrest was also inhibited by DC (0.5 ug/mL).
      Tetracycline and minocycline also showed similar anti-apoptotic effects but were
      not significant when compared to DC, tested at same concentrations. Further, DC
      (0.01-16 ug/mL) did not influence the hydrogen peroxide- or cisplatin-induced
      intrinsic apoptotic pathway in HeLa cells. Protein analysis using Western
      blotting confirmed that FasL-induced cleavage/activation of caspase-8 and caspase
      3, were inhibited by DC treatment at low concentration (0.5 ug/mL). Considering
      the overall data, we report for the first time that DC exhibited anti-apoptotic
      effects at low concentrations in HeLa cells by inhibition of caspase activation
      via FasL-induced extrinsic pathway.

PMID- 26205794
TI  - A winged scapula and dropped wrist: an unusual manifestation of copper
      deficiency.

PMID- 26205795
TI  - Neoinnervation and neovascularization of acellular pericardial-derived scaffolds
      in myocardial infarcts.
AB  - Engineered bioimplants for cardiac repair require functional vascularization and
      innervation for proper integration with the surrounding myocardium. The aim of
      this work was to study nerve sprouting and neovascularization in an acellular
      pericardial-derived scaffold used as a myocardial bioimplant. To this end, 17
      swine were submitted to a myocardial infarction followed by implantation of a
      decellularized human pericardial-derived scaffold. After 30 days, animals were
      sacrificed and hearts were analyzed with hematoxylin/eosin and Masson's and
      Gallego's modified trichrome staining. Immunohistochemistry was carried out to
      detect nerve fibers within the cardiac bioimplant by using betaIII tubulin and
      S100 labeling. Isolectin B4, smooth muscle actin, CD31, von Willebrand factor,
      cardiac troponin I, and elastin antibodies were used to study scaffold
      vascularization. Transmission electron microscopy was performed to confirm the
      presence of vascular and nervous ultrastructures. Left ventricular ejection
      fraction (LVEF), cardiac output (CO), stroke volume, end-diastolic volume, end
      systolic volume, end-diastolic wall mass, and infarct size were assessed by using
      magnetic resonance imaging (MRI). Newly formed nerve fibers composed of several
      amyelinated axons as the afferent nerve endings of the heart were identified by
      immunohistochemistry. Additionally, neovessel formation occurred spontaneously as
      small and large isolectin B4-positive blood vessels within the scaffold. In
      summary, this study demonstrates for the first time the neoformation of vessels
      and nerves in cell-free cardiac scaffolds applied over infarcted tissue.
      Moreover, MRI analysis showed a significant improvement in LVEF (P = 0.03) and CO
      (P = 0.01) and a 43 % decrease in infarct size (P = 0.007). 

PMID- 26205796
TI  - [Paroxysmal nocturnal hemoglobinuria: An unknown cause of thrombosis?].
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of
      hematopoietic stem cells. Somatic mutation in the phosphatidylinositol glycan
      class A (PIG-A), X-linked gene, is responsible for a deficiency in
      glycosphosphatidylinositol-anchored proteins (GPI-AP). The lack of one of the GPI
      AP complement regulatory proteins (CD55, CD59) leads to hemolysis. The disease is
      diagnosed with hemolytic anemia, marrow failure and thrombosis. Thromboembolic
      complication occurs in 30% of patient after 10 years of follow-up and is the
      first event in one out of 10 patients. The two most common sites are hepatic and
      cerebral veins. These locations are correlated with high risk of death.
      Currently, these data are balanced with the use of a monoclonal antibody
      (Eculizumab), which has significantly improved the prognosis with a survival
      similar to general population after 36 months of follow-up. Anticoagulant
      treatment is recommended after a thromboembolic event but has no place in primary
      prophylaxis.

PMID- 26205797
TI  - [Prevention of venous thromboembolic events by fondaparinux 2.5 mg in general
      practice. ArchiMed Ville].
AB  - OBJECTIVE: To evaluate the mean duration of treatment course with fondaparinux
      2.5 mg (ARIXTRA((r))) in the setting of ambulatory general medicine, with respect
      to its indication in thromboprophylaxis for medically ill patients and to
      describe the population treated. METHODS: Observational, prospective, national,
      multicenter, pharmaco-epidemiological study, performed in France, at the request
      of the Transparency Commission (a division of the French Health Regulatory
      Authority). The general practitioners had to include the first three adult
      patients, considered as patients at high risk of venous thromboembolic events and
      immobilized for acute medical illness, treated with initiation of
      thromboprophylaxis by fondaparinux 2.5 mg. RESULTS: Two hundred and seventeen
      general practitioners included 840 patients. The mean age of patients was 63.6+/
      18.1 years, and 63% of patients (n=520/831) were females. The real total
      administration duration of the treatment by fondaparinux 2.5 mg was known for 797
      patients and was 15.8+/-12.4 days on average (range: 1-90 days, median: 10 days).
      In 40% of patients, the duration ranged from 6 to 14 days [duration consistent
      with the summary of product characteristics (SmPC)]. Among the 834 patients
      analyzed, 569 (68%) suffered from at least one acute illness and had at least one
      risk factor for venous thromboembolism (VTE). The indication did fully comply
      with the summary of product characteristics of fondaparinux 2.5 mg in 52% of the
      patients (n=434/834 patients). CONCLUSION: The results of the ArchiMed study
      support that the thromboprophylaxis treatment with fondaparinux 2.5 mg in
      ambulatory general medicine, and the associated medical conditions were usually
      consistent with the SmPC or guidelines. However, a difference was found for the
      duration and the initial indication, in situations that may be regarded as
      presenting a risk by the prescriber.

PMID- 26205798
TI  - Catheter related line sepsis resulting from Mycobacterium chelonae infection in
      an immunocompromised host.
AB  - Almost any species of non tuberculosis mycobacterium [NTM], including M. chelonae
      may be associated with nosocomial infections including catheter related sepsis,
      pneumonia etc. We present a case of catheter related sepsis due to M. chelonae
      which was treated with appropriate therapy including removal of the catheter.
      This case serves as a reminder to include the NTM group in the differential
      diagnosis of these nosocomial infections. 

PMID- 26205799
TI  - Effect of piperine on liver function of CF-1 albino mice.
AB  - BACKGROUND: Piperine is isolated from Piper nigrum popularly known as black
      pepper. Previous studies have demonstrated the beneficial effects of piperine in
      various health conditions. Additionally, it is a powerful bioenhancer for many
      drugs. Piperine extract is believed to potentiate the effect of drugs by several
      folds. The present study is focused on its individual effect on liver function.
      MATERIALS AND METHODS: A total of 30 CF-1 albino mice obtained from the animal
      house of faculty of Medicine, Benghazi University, Benghazi, Libya were included
      in the study. These mice were fed with high cholesterol diet and divided into 2
      groups. Twenty mice were administered piperine at a dose of 5mg/kg body weight.
      Piperine was isolated in Department of Pharmacognosy, Faculty of Pharmacy,
      Benghazi University, Benghazi and 10 mice were not administered piperine but fed
      with high fat diet. These mice were anesthetized with ketamine and halothane and
      blood was drawn from each mouse before the study and after three weeks by
      cardiocentesis. Serum transaminases (alanine aminotransferase [ALT] and aspartate
      aminotransferase [AST]), alkaline phosphatase and total protein were measured by
      authenticated methods. RESULTS: Serum alanine amino transferase was significantly
      elevated (p=0.0002) in group A mice after the administration of Piperine extract
      for three weeks compared to those of group B mice. Serum aspartate amino
      transferase was elevated significantly (p=0.046) and alkaline phosphatase (p=
      0.0001) also was significantly increased after the administration of piperine.
      Serum total protein (p= 0.011) values were significantly decreased after the use
      of piperine for three weeks in group A mice. CONCLUSION: This study showed that
      there might have been a considerable damage to liver with piperine extract.
      Further research may be required to prove this damage to liver function.

PMID- 26205800
TI  - Genotyping of ESBL producing uropathogenic and diarrheagenic Escherichia coli in
      southeast of Iran.
AB  - BACKGROUND: The purpose of the present study was the distribution of blaOXA-1,
      blaPER-1 and blaVEB genes and the genotyping of these genes in extended-spectrum
      beta-lactamases (ESBL) producing uropathogenic and diarrheagenic Escherichia coli
      isolates. METHODS: Of 432 isolates, 58 uropathogenic E. coli (UPEC) and 56
      diarrheagenic E. coli (DEC) isolates were shown to produce the ESBLs. The
      isolates were screened to present ESBLs genes by PCR. Pulsed-Field Gel
      Electrophoresis (PFGE) was used to genotype E. coli strains which possess ESBLs
      genes. RESULTS: The blaOXA-1 gene was detected in 17.24% of UPEC isolates and
      1.78% of DEC isolates. Of all the isolates studied, none were positive for the
      blaPER-1 and blaVEB genes. PFGE revealed that the E. coli isolates possessed
      blaOXA-1 gene comprised three distinct genotypes. CONCLUSIONS: The current study
      illustrated high rates of ESBL-resistant phenotypes of E. coli isolates from
      urine and diarrhea samples in Iran. The blaOXA-1, blaPER-1 and blaVEB genes were
      found at low frequencies in studied isolates.

PMID- 26205801
TI  - Therapeutic efficacy of different iron chelators in Egyptian children with Beta
      Thalassemia with iron overload.
AB  - BACKGROUNDS: Beta thalassemia is a hereditary blood disorder characterized by
      reduced or absent beta chains of hemoglobin resulting in imbalanced globin chain
      synthesis with early destruction of RBCs and anemia. Patients with thalassemia
      major become transfusion- dependent with subsequent iron overload. Effective iron
      chelation therapy remains the main target of management of thalassemia major.
      OBJECTIVES: 'The aim of this work was to compare the efficacy of different iron
      chelating agents' in the treatment of ' iron overload in children with beta
      thalassemia major'. PATIENTS AND METHODS: 'The current study was conducted on 120
      children with beta thalassemia major with serum ferritin level of more than 1000
      ng/ml who were divided into 4 groups': Group A: 30 patients were treated with 8
      hours intravenous infusion of Desferrioxamine, '40 mg/kg/day, 6 days per week for
      6 months'. Group B: 30 patients were treated with subcutaneous infusion of
      Desferrioxamine, 40 mg/kg/day, 6 days per week 8-12 hours per day at night using
      Desferal pump for 6 months. Group C: 30 patients were treated with oral
      Deferiprone 75 mg/kg/day in three divided doses daily for 6 months. Group D: 30
      patients were treated with oral Deferasirox 30 mg/kg/day in single dose on empty
      stomach daily for 6 months. 'For all patients laboratory investigations were
      carried out including complete blood count (CBC), measurement of serum ferritin,
      serum iron, TIBC (total iron binding capacity), liver enzymes and kidney
      functions'. RESULTS: There were significant reductions in 'serum ferritin and
      serum iron' after treatment in all studied groups with the highest reduction in
      group A, group B, group D and group C but without statistically significant
      differences between the four studied groups before and after chelation therapy.
      'There were no significant differences in' the mean values of the parameters of
      CBC, liver enzymes and kidney functions between the studied groups before and
      after chelation therapy. CONCLUSION: From this study we concluded that there was
      significant reduction in serum ferritin and serum iron after chelation therapy in
      studied groups with the highest reduction in group A (IV Desferrioxamine), group
      B (SC Desferrioxamine), group D (oral Deferasirox) and group C (oral Deferiprone)
      with no statistically significant differences between the studied groups of
      patients before and after 6 months of regular chelation.

PMID- 26205802
TI  - Identification of potential drug targets in Helicobacter pylori strain HPAG1 by
      in silico genome analysis.
AB  - Helicobacter pylori colonizes the stomach, causing gastritis, peptic ulcers and
      gastric carcinoma. Drugs for treatment of H. pylori relieve from gastritis or
      pain but are not specific to H. pylori. Therefore, there is an immediate
      requirement for new therapeutic molecules to treat H. pylori. Current study
      investigates identification of drug targets in the strain HPAG1 of H. pylori by
      in silico genome analysis. Genome of HPAG1 was reconstructed for metabolic
      pathways and compared with Homosapien sapiens to identify genes which are unique
      to H. pylori. These unique genes were subjected to gene property analysis to
      identify the potentiality of the drug targets. Among the total number of genes
      analysed in H. pylori strain HPAG1, nearly 542 genes qualified as unique
      molecules and among them 29 were identified to be potential drug targets.
      Co/Zn/Cd efflux system membrane fusion protein, Ferric sidephore transport system
      and biopolymer transport protein EXbB were found to be critical drug targets to
      H. pylori HPAG1. Five genes (superoxide dismutase, HtrA protease/chaperone
      protein, Heatinducible transcription repressor HrcA, HspR, transcriptional
      repressor of DnaK operon, Cobalt-zinccadmium resistance protein CzcA) of the 29
      predicted drug targets are already experimentally validated either genetically or
      biochemically lending credence to our unique approach. 

PMID- 26205803
TI  - Hydrazones as a privileged structural linker in antitubercular agents: a review.
AB  - Hydrazones are a versatile linker of connecting various classes of organic
      compounds with a unique structural feature of hydrogen bonding donor and the
      hydrogen bonding acceptor region. An extensive number of research has been
      carried out on hydrazone derivatives as a potent class of antitubercular agents.
      The present review focuses on the chemistry, antitubercular activity and
      structure activity relationship (SAR) of diverse classes of phenyl and
      heterocyclic based hydrazones. 

PMID- 26205804
TI  - Coccidioidomycosis involving the cranium: a case report and review of current
      literature.
AB  - We report a case of Coccidioidomycosis of the cranium that presented as a
      cystlike structure with adjoining bone destruction in a 40-year-old patient with
      underlying rheumatoid arthritis that was treated with a combination of lipid
      amphotericin B and longterm fluconazole. We also discuss the common risk factors
      and presentations of this unusual extra-pulmonary form of Coccidioidomycosis. 

PMID- 26205805
TI  - Identification and optimization of parameters for the semi-continuous production
      of garbage enzyme from pre-consumer organic waste by green RP-HPLC method.
AB  - Reuse and management of organic solid waste, reduce the environmental impact on
      human health and increase the economic status by generating valuable products for
      current and novel applications. Garbage enzyme is one such product produced from
      fermentation of organic solid waste and it can be used as liquid fertilizer,
      antimicrobial agents, treatment of domestic wastewater, municipal and industrial
      sludge treatment, etc. The semi-continuous production of garbage enzyme in large
      quantity at minimal time period and at lesser cost is needed to cater for
      treatment of increasing quantities of industrial waste activated sludge. This
      necessitates a parameter for monitoring and control for the scaling up of current
      process on semi-continuous basis. In the present study a RP-HPLC (Reversed Phase
      High Performance Liquid Chromatography) method is used for quantification of
      standard organic acid at optimized condition 30 degrees C column oven
      temperature, pH 2.7, and 0.7 ml/min flow rate of the mobile phase (potassium
      dihydrogen phosphate in water) at 50mM concentration. The garbage enzyme solution
      collected in 15, 30, 45, 60, 75 and 90 days were used as sample to determine the
      concentration of organic acid. Among these, 90th day sample showed the maximum
      concentration of 78.14 g/l of acetic acid in garbage enzyme, whereas other
      organic acids concentration got decreased when compare to the 15th day sample.
      This result confirms that the matured garbage enzyme contains a higher
      concentration of acetic acid and thus it can be used as a monitoring parameter
      for semi-continuous production of garbage enzyme in large scale.

PMID- 26205806
TI  - Ferrocene-isocoumarin conjugated molecules: synthesis, structural
      characterization, electronic properties, and DFT-TDDFT computational study.
AB  - Two ferrocene-isocoumarin conjugated molecules, methyl 3-ferrocenyl-1-oxo-1H
      isochromene-6-carboxylate () and 3,8-bisferrocenylpyrano[3,4-g]isochromene-1,6
      dione (), have been synthesized through the acid-prompted regioselective
      oxidative cyclization from dimethyl 2-(ferrocenylethynyl)terephthalate () and
      dimethyl 2,5-bis(ferrocenylethynyl)terephthalate (), respectively. Single-crystal
      X-ray diffraction, together with the density functional theory (DFT)
      calculations, shows that the ferrocene-isocoumarin conjugated compounds display
      better coplanarity than the corresponding ferrocenylethynyl terephthalates. All
      the compounds exhibit characteristic MLCT, ICT and pi-pi* transitions in the UV
      visible range in solution, and and show higher oscillator strength of the
      absorption than and , which are verified by time-dependent DFT (TDDFT)
      theoretical calculations. The electrochemical properties are studied by cyclic
      voltammetry (CV), which are also in accord with the theoretical calculations. 

PMID- 26205807
TI  - The effects of hyperoxaemia on tissue oxygenation in patients with a nadir
      haematocrit lower than 20% during cardiopulmonary bypass.
AB  - Excessive haemodilution and the resulting anaemia during CPB is accompanied by a
      decrease in the total arterial oxygen content, which may impair tissue oxygen
      delivery. Hyperoxic ventilation has been proven to improve tissue oxygenation in
      different pathophysiological states of anaemic tissue hypoxia. The aim of this
      study was to examine the influence of arterial hyperoxaemia on tissue oxygenation
      during CPB. Records of patients undergoing isolated CABG with CPB were
      retrospectively reviewed. Patients with nadir haematocrit levels below 20% during
      CPB were included in the study. Tissue hypoxia was defined as hyperlactataemia
      (lactate >2.2 mmol/L) coupled with low ScVO2 (ScVO2 <70%) during CPB. One hundred
      patients with normoxaemia and 100 patients with hyperoxaemia were included in the
      study. Patients with hyperoxaemia had lower tissue hypoxia incidence than
      patients with normoxaemia (p<0.001). Compared with patients without tissue
      hypoxia, patients with tissue hypoxia had significantly lower PaO2 values
      (p<0.001) and nadir haematocrit levels (p<0.001). Nadir haematocrit levels <18%
      (OR: 5.3; 95% CI: 2.67-10.6; p<0.001) and hyperoxaemia (OR: 0.28; 95% CI: 0.14
      0.56; p<0.001) were independently associated with tissue hypoxia. CONCLUSIONS:
      Hyperoxaemia during CPB may be protective against tissue hypoxia in patients with
      nadir haematocrit levels <20%.

PMID- 26205808
TI  - Veno-arterial extracorporeal membrane oxygenation support for severe cardiac
      failure in a pediatric patient with intracranial hemorrhage after spontaneous
      aneurysmatic rupture.
AB  - INTRODUCTION: Extracorporeal life support in adult patients with extended
      intracranial hemorrhage is controversial. In pediatric patients, it has
      traditionally been considered a contraindication as systemic anticoagulation may
      worsen the hemorrhage and neurological outcome. CASE HISTORY: We present a nine
      year-old female patient who was admitted with extended intracranial hemorrhage
      after spontaneous rupture of an aneurysm. On day four after the emergency
      craniotomy, she required veno-arterial extracorporeal membrane oxygenation for
      septic shock. Using an adapted anticoagulation protocol aimed at lower activated
      partial thromboplastin time target values, we did not observe any new bleeding or
      clotting complications during systemic anticoagulation and the patient had good
      neurological recovery. CONCLUSION: Extracorporeal life support with low dose
      systemic anticoagulation can be considered as a treatment option in pediatric
      patients after craniotomy for intracranial aneurysmatic hemorrhage.

PMID- 26205809
TI  - Where Children With ADHD Direct Visual Attention During Emotion Knowledge Tasks:
      Relationships to Accuracy, Response Time, and ADHD Symptoms.
AB  - OBJECTIVE: Inattention may contribute to emotion recognition deficits in children
      with ADHD. In the current study, we compared the viewing patterns for emotion
      stimuli between children with and without ADHD and examined the relationship
      between viewing patterns, emotion knowledge accuracy, response time, and ADHD
      symptoms. METHOD: Eye-tracking technology recorded viewing patterns for emotion
      stimuli among 45 children (60% male; control n = 26, ADHD n = 19). RESULTS:
      Overall, viewing patterns of children with and without ADHD were strikingly
      similar; however, small to large effect sizes (Cohen's d = -0.73 to 0.93) across
      emotions suggest that, for some emotions, children with ADHD spend less time
      viewing relevant areas of images and take longer to respond (i.e., detect an
      emotion) compared with children without ADHD. CONCLUSION: Children with ADHD view
      some emotions differently from children without ADHD. The results provide an
      important foundation for additional work in this area.

PMID- 26205810
TI  - Early stage signet ring cell carcinoma of the colon examined by magnifying
      endoscopy with narrow-band imaging: a case report.
AB  - BACKGROUND: Signet ring cell carcinoma of the colon and rectum is rare, and most
      cases are detected at an advanced stage. We present a case of primary signet ring
      cell carcinoma detected at an early stage by magnifying endoscopy with narrow
      band imaging (NBI) and crystal violet staining. CASE PRESENTATION: A 73-year-old
      man visited our hospital for screening colonoscopy. Six years previously, he had
      undergone endoscopic submucosal dissection (ESD) for early gastric cancer. The
      pathological diagnosis was a well-differentiated adenocarcinoma, invading into
      the mucosa without lymphovascular invasion. Colonoscopy revealed a flat elevated
      lesion with a slightly depressed area, 20 mm in diameter, in the cecum. Further,
      magnifying endoscopy with NBI revealed that the surface pattern was slightly
      irregular and microvessels had a regular diameter and distribution in the margin
      of the lesion, but in the central part of the lesion, irregularity in the tumor
      surface pattern and form as well as in the diameter and distribution of
      microvessels was noted. Additionally, due to mucus, avascular areas were also
      observed. Magnifying endoscopy combined with 0.05 % crystal violet staining
      showed IIIL and VI pit patterns in the margin of the lesion, and a VI pit pattern
      in the central part of the lesion; however, due to mucus exudate, this finding
      could not be established with certainty. The lesion was successfully removed en
      bloc using ESD without complications. The tumor was composed mainly of signet
      ring cell carcinoma, partially mixed with moderately differentiated (tub2) and
      well-differentiated (tub1) adenocarcinomas. The tumor cells infiltrated 250 MUm
      into the submucosal layer and involved lymphatic vessels. Therefore, the patient
      underwent an additional laparoscopic ileocecal resection, and the resected
      specimen revealed no residual carcinoma or lymph node metastasis. CONCLUSION: In
      this case report, we present a case of primary signet ring cell carcinoma
      detected at an early stage and identified by magnifying endoscopy with NBI and
      crystal violet staining.

PMID- 26205813
TI  - Endocytosis: Is There Really a Recycling from Late Endosomes?

PMID- 26205811
TI  - Expression analysis of NOS family and HSP genes during thermal stress in goat
      (Capra hircus).
AB  - Approximately 50 genes other than heat shock protein (HSP) expression changes
      during thermal stress. These genes like nitric oxide synthase (NOS) need proper
      attention and investigation to find out their possible role in the adaptation to
      thermal stress in animals. So, the present study was undertaken to demonstrate
      the expressions of inducible form type II NOS (iNOS), endothelial type III NOS
      (eNOS), constitutively expressed enzyme NOS (cNOS), HSP70, and HSP90 in
      peripheral blood mononuclear cells (PBMCs) during different seasons in Barbari
      goats. Real-time polymerase chain reaction, western blot, and immunocytochemistry
      were applied to investigate messenger RNA (mRNA) expression, protein expression,
      and immunolocalization of examined factors. The mRNA and protein expressions of
      iNOS, eNOS, cNOS, HSP70, and HSP90 were significantly higher (P < 0.05) during
      peak summer, and iNOS and eNOS expressions were also observed to be significantly
      higher (P < 0.05) during peak winter season as compared with moderate season. The
      iNOS, eNOS, cNOS, HSP70, and HSP90 were mainly localized in plasma membrane and
      cytoplasm of PBMCs. To conclude, data generated in the present study indicate the
      possible involvement of the NOS family genes in amelioration of thermal stress so
      as to maintain cellular integrity and homeostasis in goats. 

PMID- 26205814
TI  - Environmental Stress and Pre-mRNA Splicing.

PMID- 26205815
TI  - Characterization of a single b-type heme, FAD, and metal binding sites in the
      transmembrane domain of six-transmembrane epithelial antigen of the prostate
      (STEAP) family proteins.
AB  - Six-transmembrane epithelial antigen of the prostate 3 (Steap3) is the major
      ferric reductase in developing erythrocytes. Steap family proteins are defined by
      a shared transmembrane domain that in Steap3 has been shown to function as a
      transmembrane electron shuttle, moving cytoplasmic electrons derived from NADPH
      across the lipid bilayer to the extracellular face where they are used to reduce
      Fe(3+) to Fe(2+) and potentially Cu(2+) to Cu(1+). Although the cytoplasmic N
      terminal oxidoreductase domain of Steap3 and Steap4 are relatively well
      characterized, little work has been done to characterize the transmembrane domain
      of any member of the Steap family. Here we identify high affinity FAD and iron
      biding sites and characterize a single b-type heme binding site in the Steap3
      transmembrane domain. Furthermore, we show that Steap3 is functional as a
      homodimer and that it utilizes an intrasubunit electron transfer pathway through
      the single heme moiety rather than an intersubunit electron pathway through a
      potential domain-swapped dimer. Importantly, the sequence motifs in the
      transmembrane domain that are associated with the FAD and metal binding sites are
      not only present in Steap2 and Steap4 but also in Steap1, which lacks the N
      terminal oxidoreductase domain. This strongly suggests that Steap1 harbors latent
      oxidoreductase activity. 

PMID- 26205816
TI  - Ambient Light Promotes Selective Subcellular Proteotoxicity after Endogenous and
      Exogenous Porphyrinogenic Stress.
AB  - Hepatic accumulation of protoporphyrin-IX (PP-IX) in erythropoietic
      protoporphyria (EPP) or X-linked-dominant protoporphyria (XLP) cause liver
      damage. Hepatocyte nuclear lamin aggregation is a sensitive marker for PP-IX
      mediated liver injury. We tested the hypothesis that extracellular or
      intracellular protoporphyria cause damage to different subcellular compartments,
      in a light-triggered manner. Three hepatoma cell lines (HepG2, Hepa-1, and Huh-7)
      were treated with exogenous PP-IX (mimicking XLP extrahepatic protoporphyria) or
      with the iron chelator deferoxamine and the porphyrin precursor 5-aminolevulinic
      acid (ALA) (mimicking intracellular protoporphyrin accumulation in EPP).
      Exogenous PP-IX accumulated predominantly in the nuclear fraction and caused
      nuclear shape deformation and cytoplasmic vacuoles containing electron-dense
      particles, whereas ALA+deferoxamine treatment resulted in higher PP-IX in the
      cytoplasmic fraction. Protein aggregation in the nuclear and cytoplasmic
      fractions paralleled PP-IX levels and, in cell culture, the effects were
      exclusively ambient light-mediated. PP-IX and ALA caused proteasomal inhibition,
      whereas endoplasmic reticulum protein aggregation was more prominent in ALA
      treated cells. The enhanced ALA-related toxicity is likely due to generation of
      additional porphyrin intermediates including uroporphyrin and coproporphyrin,
      based on HPLC analysis of cell lysates and the culture medium, as well as cell
      free experiments with uroporphyrin/coproporphyrin. Mouse livers from drug-induced
      porphyria phenocopied the in vitro findings, and mass spectrometry of liver
      proteins isolated in light/dark conditions showed diminished (as compared with
      light-harvested) but detectable aggregation under dark-harvested conditions.
      Therefore, PP-IX leads to endoplasmic reticulum stress and proteasome inhibition
      in a manner that depends on the source of porphyrin buildup and light exposure.
      Porphyrin-mediated selective protein aggregation provides a potential mechanism
      for porphyria-associated tissue injury. 

PMID- 26205817
TI  - Structure-Function Analysis of the Mcl-1 Protein Identifies a Novel Senescence
      regulating Domain.
AB  - Unlike other antiapoptotic Bcl-2 family members, Mcl-1 also mediates resistance
      to cancer therapy by uniquely inhibiting chemotherapy-induced senescence (CIS).
      In general, Bcl-2 family members regulate apoptosis at the level of the
      mitochondria through a common prosurvival binding groove. Through mutagenesis, we
      determined that Mcl-1 can inhibit CIS even in the absence of its apoptotically
      important mitochondrion-localizing domains. This finding prompted us to generate
      a series of Mcl-1 deletion mutants from both the N and C termini of the protein,
      including one that contained a deletion of all of the Bcl-2 homology domains,
      none of which impacted anti-CIS capabilities. Through subsequent structure
      function analyses of Mcl-1, we identified a previously uncharacterized loop
      domain responsible for the anti-CIS activity of Mcl-1. The importance of the loop
      domain was confirmed in multiple tumor types, two in vivo models of senescence,
      and by demonstrating that a peptide mimetic of the loop domain can effectively
      inhibit the anti-CIS function of Mcl-1. The results from our studies appear to be
      highly translatable because we discerned an inverse relationship between the
      expression of Mcl-1 and of various senescence markers in cancerous human tissues.
      In summary, our findings regarding the unique structural properties of Mcl-1
      provide new approaches for targeted cancer therapy. 

PMID- 26205818
TI  - Nonantibiotic Effects of Fluoroquinolones in Mammalian Cells.
AB  - Fluoroquinolones (FQ) are powerful broad-spectrum antibiotics whose side effects
      include renal damage and, strangely, tendinopathies. The pathological mechanisms
      underlying these toxicities are poorly understood. Here, we show that the FQ
      drugs norfloxacin, ciprofloxacin, and enrofloxacin are powerful iron chelators
      comparable with deferoxamine, a clinically useful iron-chelating agent. We show
      that iron chelation by FQ leads to epigenetic effects through inhibition of alpha
      ketoglutarate-dependent dioxygenases that require iron as a co-factor. Three
      dioxygenases were examined in HEK293 cells treated with FQ. At sub-millimolar
      concentrations, these antibiotics inhibited jumonji domain histone demethylases,
      TET DNA demethylases, and collagen prolyl 4-hydroxylases, leading to accumulation
      of methylated histones and DNA and inhibition of proline hydroxylation in
      collagen, respectively. These effects may explain FQ-induced nephrotoxicity and
      tendinopathy. By the same reasoning, dioxygenase inhibition by FQ was predicted
      to stabilize transcription factor HIF-1alpha by inhibition of the oxygen
      dependent hypoxia-inducible transcription factor prolyl hydroxylation. In
      dramatic contrast to this prediction, HIF-1alpha protein was eliminated by FQ
      treatment. We explored possible mechanisms for this unexpected effect and show
      that FQ inhibit HIF-1alpha mRNA translation. Thus, FQ antibiotics induce global
      epigenetic changes, inhibit collagen maturation, and block HIF-1alpha
      accumulation. We suggest that these mechanisms explain the classic renal
      toxicities and peculiar tendinopathies associated with FQ antibiotics. 

PMID- 26205819
TI  - Characterization of Dye-decolorizing Peroxidase (DyP) from Thermomonospora
      curvata Reveals Unique Catalytic Properties of A-type DyPs.
AB  - Dye-decolorizing peroxidases (DyPs) comprise a new family of heme peroxidases,
      which has received much attention due to their potential applications in lignin
      degradation. A new DyP from Thermomonospora curvata (TcDyP) was identified and
      characterized. Unlike other A-type enzymes, TcDyP is highly active toward a wide
      range of substrates including model lignin compounds, in which the catalytic
      efficiency with ABTS (kcat(app)/Km(app) = (1.7 * 10(7)) m(-1) s(-1)) is close to
      that of fungal DyPs. Stopped-flow spectroscopy was employed to elucidate the
      transient intermediates as well as the catalytic cycle involving wild-type (wt)
      and mutant TcDyPs. Although residues Asp(220) and Arg(327) are found necessary
      for compound I formation, His(312) is proposed to play roles in compound II
      reduction. Transient kinetics of hydroquinone (HQ) oxidation by wt-TcDyP showed
      that conversion of the compound II to resting state is a rate-limiting step,
      which will explain the contradictory observation made with the aspartate mutants
      of A-type DyPs. Moreover, replacement of His(312) and Arg(327) has significant
      effects on the oligomerization and redox potential (E degrees ') of the enzyme.
      Both mutants were found to promote the formation of dimeric state and to shift E
      degrees ' to a more negative potential. Not only do these results reveal the
      unique catalytic property of the A-type DyPs, but they will also facilitate the
      development of these enzymes as lignin degraders.

PMID- 26205820
TI  - Apoglobin Stability Is the Major Factor Governing both Cell-free and in Vivo
      Expression of Holomyoglobin.
AB  - Expression levels in animal muscle tissues and in Escherichia coli vary widely
      for naturally occurring mammalian myoglobins (Mb). To explore this variation, we
      developed an in vitro transcription and wheat germ extract-based translation
      assay to examine quantitatively the factors that govern expression of holoMb. We
      constructed a library of naturally occurring Mbs from two terrestrial and four
      deep-diving aquatic mammals and three distal histidine mutants designed to
      enhance apoglobin stability but decrease hemin affinity. A strong linear
      correlation is observed between cell-free expression levels of holo-metMb
      variants and their corresponding apoglobin stabilities, which were measured
      independently by guanidine HCl-induced unfolding titrations using purified
      proteins. In contrast, there is little dependence of expression on hemin
      affinity. Our results confirm quantitatively that deep diving mammals have highly
      stable Mbs that express to higher levels in animal myocytes, E. coli, and the
      wheat germ cell-free system than Mbs from terrestrial mammals. Our theoretical
      analyses show that the rate of aggregation of unfolded apoMb is very large, and
      as a result, the key factor for high level expression of holoMb, and presumably
      other heme proteins, is an ultra high fraction of folded, native apoglobin that
      is capable of rapidly binding hemin. This fraction is determined by the overall
      equilibrium folding constant and not hemin affinity. These results also
      demonstrate that the cell-free transcription/translation system can be used as a
      high throughput platform to screen for apoglobin stability without the need to
      generate large amounts of protein for in vitro unfolding measurements. 

PMID- 26205821
TI  - PAX3 and FOXD3 Promote CXCR4 Expression in Melanoma.
AB  - Metastatic melanoma is an aggressive and deadly disease. The chemokine receptor
      CXCR4 is active in melanoma metastasis, although the mechanism for the promotion
      and maintenance of CXCR4 expression in these cells is mostly unknown. Here, we
      find melanoma cells express two CXCR4 isoforms, the common version and a variant
      that is normally restricted to cells during development or to mature blood cells.
      CXCR4 expression is driven through a highly conserved intronic enhancer element
      by the transcription factors PAX3 and FOXD3. Inhibition of these transcription
      factors slows melanoma cell growth, migration, and motility, as well as reduces
      CXCR4 expression. Overexpression of these transcription factors drives the
      production of increased CXCR4 levels. Loss of PAX3 and FOXD3 transcription factor
      activity results in a reduction in cell motility, migration, and chemotaxis, all
      of which are rescued by CXCR4 overexpression. Here, we discover a molecular
      pathway wherein PAX3 and FOXD3 promote CXCR4 gene expression in melanoma. 

PMID- 26205823
TI  - A Survey of Caregiver Perspectives on Children's Pain Management in the Emergency
      Department.
AB  - OBJECTIVES: We explored caregiver perspectives on their children's pain
      management in both a pediatric (PED) and general emergency department (GED).
      Study objectives were to: (1) measure caregiver estimates of children's pain
      scores and treatment; (2) determine caregiver level of satisfaction; and (3)
      determine factors associated with caregiver satisfaction. METHODS: This
      prospective survey examined a convenience sample of 97 caregivers (n=51 PED, n=46
      GED) with children aged <17 years. A paper-based survey was distributed by
      research assistants, from 2009-2011. RESULTS: Most caregivers were female (n=77,
      79%) and were the child's mother (n=69, 71%). Children were treated primarily for
      musculoskeletal pain (n=41, 42%), headache (n=16, 16%) and abdominal pain (n=7,
      7%). Using a 100 mm Visual Analog Scale, the maximum mean reported pain score was
      75 mm (95% CI: 70-80) and mean score at discharge was 39 mm (95% CI: 32-46).
      Ninety percent of caregiver respondents were satisfied (80/89, 90%); three (3/50,
      6%) were dissatisfied in the PED and six (6/39, 15%) in the GED. Caregivers who
      rated their child's pain at ED discharge as severe were less likely to be
      satisfied than those who rated their child's pain as mild or moderate (p=0.034).
      CONCLUSIONS: Despite continued pain upon discharge, most caregivers report being
      satisfied with their child's pain management. Caregiver satisfaction is likely
      multifactorial, and physicians should be careful not to interpret satisfaction as
      equivalent to adequate provision of analgesia. The relationship between
      satisfaction and pain merits further exploration.

PMID- 26205824
TI  - Interferon-alpha treatment induces depression-like behaviour accompanied by
      elevated hippocampal quinolinic acid levels in rats.
AB  - Immunotherapy with the cytokine interferon-alpha (IFN-alpha) can induce symptoms
      of depression, and it is likely that the tryptophan-kynurenine pathway may be
      involved in this regard. In this study we investigated the effects of IFN-alpha
      on depression-like behaviour and central metabolites of the tryptophan-kynurenine
      pathway in rats. Secondly, we explored the modulating effects of an
      antidepressant (imipramine) and anti-inflammatory drug (celecoxib) on IFN-alpha
      induced behavioural and pathophysiological changes in the brain. The following
      treatment groups were used: Control (saline), IFN-alpha (6*10(4)IU/kg s.c.), IFN
      alpha+imipramine or IFN-alpha+celecoxib. Drugs were administered daily for 1
      week. IFN-alpha treatment induced depression-like behaviour by increasing
      immobility in the forced swim test (FST), and decreased tryptophan levels in the
      brain. There was a trend for an increased kynurenine/tryptophan ratio, indicative
      of indoleamine 2,3-dioxygenase (IDO) activation, and increased quinolinic acid in
      the hippocampus. Imipramine decreased immobility in the FST, but did not reverse
      the IFN-alpha-induced changes in the tryptophan-kynurenine pathway. There was a
      trend for celecoxib to decrease immobility and to reverse the IFN-alpha-induced
      increase in the kynurenine/tryptophan ratio. Thus, our study provides further
      evidence for IFN-alpha-induced depression-like behaviour through central changes
      of the tryptophan-kynurenine pathway. 

PMID- 26205822
TI  - ERManI (Endoplasmic Reticulum Class I alpha-Mannosidase) Is Required for HIV-1
      Envelope Glycoprotein Degradation via Endoplasmic Reticulum-associated Protein
      Degradation Pathway.
AB  - Previously, we reported that the mitochondrial translocator protein (TSPO)
      induces HIV-1 envelope (Env) degradation via the endoplasmic reticulum (ER)
      associated protein degradation (ERAD) pathway, but the mechanism was not clear.
      Here we investigated how the four ER-associated glycoside hydrolase family 47
      (GH47) alpha-mannosidases, ERManI, and ER-degradation enhancing alpha-mannosidase
      like (EDEM) proteins 1, 2, and 3, are involved in the Env degradation process.
      Ectopic expression of these four alpha-mannosidases uncovers that only ERManI
      inhibits HIV-1 Env expression in a dose-dependent manner. In addition, genetic
      knock-out of the ERManI gene MAN1B1 using CRISPR/Cas9 technology disrupts the
      TSPO-mediated Env degradation. Biochemical studies show that HIV-1 Env interacts
      with ERManI, and between the ERManI cytoplasmic, transmembrane, lumenal stem, and
      lumenal catalytic domains, the catalytic domain plays a critical role in the Env
      ERManI interaction. In addition, functional studies show that inactivation of the
      catalytic sites by site-directed mutagenesis disrupts the ERManI activity. These
      studies identify ERManI as a critical GH47 alpha-mannosidase in the ER-associated
      protein degradation pathway that initiates the Env degradation and suggests that
      its catalytic domain and enzymatic activity play an important role in this
      process. 

PMID- 26205825
TI  - The impact of eye closure on somatosensory perception in the elderly.
AB  - Visual dominance over other senses is a well-known phenomenon. Closing the eyes,
      even in complete darkness, can improve somatosensory perception by switching off
      various aspects of visual dominance. How and if this mechanism is affected by
      aging remains unknown. We performed detailed neurophysiological and functional MR
      imaging on healthy young and elderly participants under the conditions of opened
      and closed eyes. We found an improved perception threshold in both groups when
      the eyes were closed, but the improvement was significantly less pronounced in
      the elderly. fMRI data revealed increased resting activity in the somatosensory
      cortex with closed eyes, and the stimulus-induced activity of the secondary
      somatosensory cortex decreased in the young but not in the elderly. This study
      demonstrates that a switch towards unisensory processing via eye closure is
      preserved but significantly reduced in the aging brain. We suggest that the
      decreased ability for unisensory processing is a general phenomenon in the aging
      brain resulting in a shift toward multisensory integration. 

PMID- 26205826
TI  - Relevance of dorsomedial hypothalamus, dorsomedial division of the ventromedial
      hypothalamus and the dorsal periaqueductal gray matter in the organization of
      freezing or oriented and non-oriented escape emotional behaviors.
AB  - Electrical stimulation of the periaqueductal gray matter and ventromedial
      hypothalamus in humans showed the involvement of both these structures in panic
      attacks. The aim of this work was to make clear the role of dorsal periaqueductal
      gray (dPAG) matter, dorsomedial hypothalamus (DMH) and the dorsomedial part of
      the ventromedial hypothalamus (dmVMH) in panic attack-like behaviors. DMH, dmVMH
      and dPAG of Wistar rats were treated with N-methyl- d-aspartic acid (NMDA) at
      different doses. The rodents were then kept in a polygonal arena with a burrow to
      record panic attack-like responses and oriented defensive behaviors. In dmVMH,
      6nmol of NMDA elicited alertness, freezing and oriented escape. The same set of
      behaviors was elicited by DMH neurons when stimulated by 9nmol of NMDA. Treatment
      of dmVMH with 9nmol of NMDA elicited typical explosive behaviors followed by
      freezing and oriented behaviors. The stimulation of the dPAG with NMDA at
      different doses provoked alertness and freezing (1nmol) or alertness, freezing,
      tail twitching, explosive behavior and oriented escape (3nmol), and explosive
      behavior followed by long-lasting freezing (6nmol). These data suggest that
      mainly dPAG plays a role in panic attack-like behaviors that resemble panic
      syndrome in humans. However, hypothalamic nuclei like dmVMH that mainly elicits
      oriented escape, can also produce explosive reaction when stimulated with 9nmol
      NMDA, whereas, DMH plays a role in coordinating defensive behaviors. 

PMID- 26205827
TI  - Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic
      inflammation and memory impairment in APP/PS1 mice.
AB  - Type 2 diabetes is a risk factor for Alzheimer's disease (AD). Previously, we
      have shown that the diabetes drug liraglutide is protective in middle aged and in
      old APP/PS1 mice. Here, we show that liraglutide has prophylactic properties.
      When injecting liraglutide once-daily ip. in two months old mice for 8 months,
      the main hallmarks of AD were much reduced. Memory formation in object
      recognition and Morris water maze were normalised and synapse loss and the loss
      of synaptic plasticity was prevented. In addition, amyloid plaque load, including
      dense core congophilic plaques, was much reduced. Chronic inflammation (activated
      microglia) was also reduced in the cortex, and neurogenesis was enhanced in the
      dentate gyrus. The results demonstrate that liraglutide may protect from
      progressive neurodegeneration that develops in AD. The drug is currently in
      clinical trials in patients with AD. 

PMID- 26205828
TI  - DNA barcode reference library for Iberian butterflies enables a continental-scale
      preview of potential cryptic diversity.
AB  - How common are cryptic species--those overlooked because of their morphological
      similarity? Despite its wide-ranging implications for biology and conservation,
      the answer remains open to debate. Butterflies constitute the best-studied
      invertebrates, playing a similar role as birds do in providing models for
      vertebrate biology. An accurate assessment of cryptic diversity in this
      emblematic group requires meticulous case-by-case assessments, but a preview to
      highlight cases of particular interest will help to direct future studies. We
      present a survey of mitochondrial genetic diversity for the butterfly fauna of
      the Iberian Peninsula with unprecedented resolution (3502 DNA barcodes for all
      228 species), creating a reliable system for DNA-based identification and for the
      detection of overlooked diversity. After compiling available data for European
      butterflies (5782 sequences, 299 species), we applied the Generalized Mixed Yule
      Coalescent model to explore potential cryptic diversity at a continental scale.
      The results indicate that 27.7% of these species include from two to four
      evolutionary significant units (ESUs), suggesting that cryptic biodiversity may
      be higher than expected for one of the best-studied invertebrate groups and
      regions. The ESUs represent important units for conservation, models for studies
      of evolutionary and speciation processes, and sentinels for future research to
      unveil hidden diversity.

PMID- 26205829
TI  - Gastrointestinal bleeding and severe anaemia: An uncommon presentation of small
      bowel carcinoma complicating ileal Crohn's disease.

PMID- 26205830
TI  - Direct antiviral agents for treatment-naive patients with genotype 1 hepatitis C:
      A statistical model for comparing outcomes between real world and clinical
      trials.

PMID- 26205831
TI  - The Importance of Rigorous Statistical Practice in the Current Landscape of QSAR
      Modelling.

PMID- 26205832
TI  - Enhanced Action Potential Passage Through the Node of Ranvier of Myelinated Axons
      via Proton Hopping.
AB  - Nerve impulses travel along myelinated axons as much as 300-fold faster than they
      do along unmyelinated axons. Myelination is essential for normal nervous system
      behavior in vertebrates as illustrated by leukodystrophies, such as amyotrophic
      lateral sclerosis (ALS) or multiple sclerosis (MS), where myelin is degenerated
      or damaged. The increased conduction velocity that occurs in myelinated axons is
      dependent on gaps in the myelin called Nodes of Ranvier that are enriched in ion
      channels. These Nodes are separated by long stretches of myelin insulation where
      no transmembrane ion conductance occurs. It is believed that the action potential
      jumps or skips between nodes, conserving its information content, while
      maintaining its speed. In this study, a model is presented that implicates Nodes
      of Ranvier as responsible for regenerating the proton hopping that is responsible
      for nerve impulse conductance in myelinated axons. 

PMID- 26205833
TI  - Factors associated with sexual risk behaviors with non-steady partners and lack
      of recent HIV testing among German men who have sex with men in steady
      relationships: results from a cross-sectional internet survey.
AB  - BACKGROUND: Recent evidence suggests that the majority of HIV transmissions among
      men who have sex with men (MSM) occur between steady partners. We sought to
      determine factors associated with HIV transmission risks in steady partnerships.
      METHODS: Data is from the German cross-sectional 2013 Gay Men and AIDS survey.
      The study population was HIV-negative or untested men reporting a steady
      partnership and at least one non-steady anal sex partner in the previous year.
      Bivariate and multivariate logistic regression was used to determine which of
      several independent variables best predicted both unprotected anal intercourse
      (UAI) with a non-steady partner and lack of HIV testing in the past year (high
      risk outcome group). RESULTS: The study population consisted of 1731 men. Among
      individuals in the outcome group (n = 271), 67% reported UAI with a non-steady
      partner of unknown status and 9% reported UAI with a non-steady HIV-positive
      partner in the past 12 months; 55% considered themselves to be at low risk for
      HIV acquisition. In multivariate analyses (n = 1304), participants were
      statistically more likely to belong to the outcome group if they reported UAI
      with their steady partner in the past year (OR = 2.21), did not know their steady
      partner's HIV status (OR = 1.98), or agreed that condoms were disruptive during
      sex (OR = 3.82 (strongly agree), OR = 2.19 (agree)). Participants were less
      likely to belong to the outcome group if they were out to their primary doctor
      (OR = 0.54), were well-educated about post-exposure prophylaxis (OR = 0.46), had
      sought information on HIV in the past year and kept condoms in an accessible
      place (OR = 0.20), or believed that insisting on condoms would lead partners to
      assume they were HIV-negative (OR = 0.20). Participants in the outcome group were
      more likely to say they would use HIV home tests (OR = 1.58) or pre-exposure
      prophylaxis (OR = 2.11). CONCLUSIONS: Based on our results, we reflect on HIV
      prevention measures that should be improved in order to better target behaviors
      that may lead to HIV transmission between MSM in steady relationships. In
      particular, we highlight the need for multifaceted interventions focusing not
      only on members of the at-risk community themselves, but on communities as a
      whole.

PMID- 26205834
TI  - Brain. Editorial.

PMID- 26205835
TI  - Monitoring brain activity in preterms: mathematics helps to predict clinical
      outcome.

PMID- 26205836
TI  - Re-evaluating the glio-centric view of multiple system atrophy by highlighting
      the neuronal involvement.

PMID- 26205837
TI  - Peripheral synuclein tissue markers: a step closer to Parkinson's disease
      diagnosis.

PMID- 26205839
TI  - Corrigendum.

PMID- 26205838
TI  - Music, memory and mechanisms in Alzheimer's disease.

PMID- 26205840
TI  - European Code against Cancer 4th Edition: Obesity, body fatness and cancer.
AB  - It is estimated that over half the population of the European Union (EU) is
      overweight or obese due to an imbalance between energy expenditure and energy
      intake; this is related to an obesogenic environment of sociocultural, economic
      and marketing challenges to the control of body weight. Excess body fat is
      associated with nine cancer sites - oesophagus, colorectum, gall bladder,
      pancreas, postmenopausal breast, endometrium, ovary, kidney and prostate
      (advanced) - and 4-38% of these cancers (depending on site and gender) can be
      attributed to overweight/obesity status. Metabolic alterations which accompany
      excess body weight are accompanied by increased levels of inflammation, insulin,
      oestrogens and other hormonal factors. There are some indications that
      intentional weight loss is associated with reduced cancer incidence (notably in
      postmenopausal breast and endometrial cancers). Excess body weight is also a risk
      factor for several other diseases, including diabetes and heart disease, and is
      related to higher risk of premature death. In reviewing the current evidence
      related to excess body fat and cancer, the European Code against Cancer Nutrition
      Working Group has developed the following recommendation: 'Take action to be a
      healthy body weight'. 

PMID- 26205841
TI  - [Diffuse pulmonary meningotheliomatosis].
AB  - In two patients with bilateral micronodular pulmonary changes a diffuse pulmonary
      meningotheliomatosis was found. A 73-year-old woman presented with bilateral
      disseminated miliary pulmonary nodules as a radiological incidental finding. The
      surgical lung biopsy showed multiple tiny nodular proliferations meningothelial
      like cells, corresponding "minute pulmonary meningothelial-like nodules", MPMN. A
      60-year-old lady with similar radiological findings showed also proliferations of
      meningothelial-like cells in a transbronchial cryo-biopsy. These lesions are well
      known to pathologists as curious isolated incidental findings on histological
      examination of lung specimens. The here described diffuse form of these changes
      is very rare; its knowledge is important for the differential diagnosis with
      neoplastic proliferations and other diffuse parenchymal diseases of the lung.
      This rare diagnosis is made on histological grounds and is also possible in
      transbronchial biopsies when careful correlation with clinical and radiological
      data, knowledge of the entity and adequate specimens are provided. 

PMID- 26205842
TI  - [Cardiopulmonary exercise testing in chronic obstructive pulmonary disease (COPD)
      - breath-functional characterization and disease severity assessment].
AB  - COPD is a heterogeneous disease with a wide range of clinical phenotypes and
      breath-functional dysfunctions. Cardiopulmonary exercise testing (CPET) allows
      describing all component parts of breathing and determining exercise capacity and
      the mechanisms of exercise limitation. From these aspects 64 COPD patient stages
      II, III and IV according to the conventional GOLD classification were examined by
      means of CPET to evaluate whether CPET can provide a better functional
      characterization of COPD than the standard investigation procedures in pulmonary
      practice.We could show that in pulmonary practice CPET is safely and effectively
      practicable in stable COPD patients of all GOLD stages. This method allowed a
      clinical and prognostic disease severity assessment of all patients, proving
      important differences of peak oxygen uptake in each GOLD stage, so that patients
      in spite of identical GOLD disease severity were to be assigned to different
      prognostic groups according CPET criteria. Furthermore, we found relevant
      differences of individual breath-functional patterns in exercise, which can
      neither be objectified nor be prognosticated by standard investigation procedures
      at rest.Therefore CPET allows, aside from an objective clinical and prognostic
      disease severity assessment, also a breath-functional evaluation in a subtly way
      in COPD patients reflecting the multidimensional background of the disease with
      variable dysfunctions in pulmonary ventilation, gas exchange, circulation and
      muscular function as well as associated cardio vascular comorbidities. The breath
      functional phenotyping of the COPD patient seems to be meaningful in particular
      for an individualised therapy management. 

PMID- 26205843
TI  - [Correct Inhalation Therapy for Patients with Cystic Fibrosis Provided by
      Internet-based Video Clips of the German Airway League].
AB  - Adolescents and young adults with cystic fibrosis (CF) are increasingly having
      difficulties to take over the complete responsibility for their daily treatment.
      Particularly inhalative therapy poses special problems. In order to overcome this
      unsatisfactory situation typically occurring during this vulnerable period, the
      German Airway League has now created a poster "Correct Inhalation Therapy For
      Patients With Cystic Fibrosis", according to the model presented by this League
      already in 2013 for correct inhalation under certain disease conditions. This
      give an opportunity to adolescents and young adults with CF to obtain
      anonymously, independently of time and location, autonomously and in a time
      saving manner information on correct inhalative treatment. Adolescents and young
      adults with CF can thus be actively supported on their way to independence.
      Furthermore, the video clips and the poster offer support physicians, nurses and
      physiotherapists and can be employed in training of all involved persons in
      inhalation techniques. 

PMID- 26205844
TI  - Ischemic stroke patients with active malignancy or extracardiac shunts are more
      likely to have a right-to-left shunt found by TCD than echocardiogram.
AB  - Although the association between patent foramen ovale and ischemic stroke is
      controversial, the evaluation for a right-to-left shunt remains part of the
      standard workup for cryptogenic stroke. Transthoracic and transesophageal
      echocardiogram (TTE and TEE) are the screening test and gold standard to evaluate
      for right-to-left shunt, respectively. Studies comparing TTE or TEE to
      transcranial Doppler (TCD) have shown that 15-25 % of patients test positive for
      right-to-left shunt on TCD but are negative on TTE or TEE. We sought to further
      explore this phenomenon in patients with recent ischemic stroke. Between 2011 and
      2013, 109 ischemic stroke patients had both a TCD and TTE or TEE bubble study. We
      abstracted 12 comorbid medical conditions and stroke subtype according to the
      TOAST classification. The majority of TCD and TTE or TEE showed agreement on
      right-to-left shunt status (80/109, 73 %). Two percent (2/109) of patients were
      negative on TCD and positive on TTE or TEE, while 25 % (27/109) had a positive
      TCD and negative TTE or TEE (TCD+Echo-). The TCD+Echo- patients were more likely
      to have active malignancy and the delayed arrival of contrast bubbles than the
      remainder of the cohort (15 vs. 2 %, p = 0.032; 51 vs. 18 %, p = 0.001). Our
      results confirm previous reports that TCD is superior to echocardiography in the
      detection of right-to-left shunt. The TCD+Echo- patients were more likely to have
      active malignancy and findings suggestive of an extracardiac shunt. These results
      could lead to more comprehensive evaluation for occult malignancy or a pulmonary
      arteriovenous malformation, both potentially treatable etiologies of ischemic
      stroke. 

PMID- 26205845
TI  - Periodic almost-Schrodinger equation for quasicrystals.
AB  - A new method for finding electronic structure and wavefunctions of electrons in
      quasiperiodic potential is introduced. To obtain results it uses slightly
      modified Schrodinger equation in spaces of dimensionality higher than physical
      space. It enables to get exact results for quasicrystals without expensive non
      exact calculations. 

PMID- 26205846
TI  - DEVO-(WO) MAN? A MOVE IN RESPECT OF PERSONAL SOVEREIGNTY AND DECISION-MAKING IN
      HEALTH CARE? Anita Border v Lewisham and Greenwich NHS Trust [2015] EWCA Civ 8.
AB  - This case commentary discusses a recent case concerning the determination of
      acceptable clinical practice. It critically examines two particular elements of
      the judgment-the method for the determination of acceptable clinical practice
      including the impact (if any) of the Bolitho exception. It then moves on to
      considering the importance of consent as a pre-requisite for medical treatment
      and the interplay of negligence and battery in this area. It concludes by
      examining the possibility that the courts in England and Wales might be entering
      an era of judicial assertiveness in the regulation of clinical practice. 

PMID- 26205847
TI  - The structure and behavior of the NA-CATH antimicrobial peptide with liposomes.
AB  - Naja atra cathelicidin (NA-CATH) is a 34-amino acid highly cationic peptide
      identified in Chinese cobras to possess potent toxicity against gram-negative and
      gram-positive bacteria and low toxicity against host cells. Here, we report the
      NMR solution structure of the full-length NA-CATH peptide and its interaction
      with liposomes. The structure shows a well-defined alpha-helix between residues
      Phe3 to Lys23, on which one surface is lined by the side-chains of one arginine
      and 11 lysine residues, while the other side is populated by hydrophobic
      residues. The last eleven amino acids, which are predominately aromatic and
      hydrophobic in nature, have no defined structure. NMR data reveal that these
      residues do not interact with the hydrophobic residues of the helix, indicating
      that the C-terminal residues have random conformations. Fluorescence requenching
      experiments, in which liposomes serve as a mimic of the bacterial membranes,
      result in fluorophore leakage that is consistent with a membrane thinning or
      transient pore formation mechanism. NMR titration studies of the peptide-liposome
      interaction reveal that the peptide is in fast exchange with the liposome,
      consistent with the fluorescent studies. These data indicate that full length NA
      CATH possesses a helical segment and unstructured C-terminal tail that disrupts
      the bilayer to induce leakage and lysing. 

PMID- 26205848
TI  - Differential proteomics of monosodium urate crystals-induced inflammatory
      response in dissected murine air pouch membranes by iTRAQ technology.
AB  - The precipitation of monosodium urate crystals within joints triggers an acute
      inflammatory reaction that is the root cause of gout. The inflammation induced by
      the injection of MSU crystals into the murine air pouch for 1, 3, and 5 h was
      examined by iTRAQ-based proteomic profiling. The iTRAQ-labeled peptides were
      fractionated by SCX, basic-RP or solution-IEF, followed by LC-MS/MS analysis. A
      total of 951 proteins were quantified from the total combined fractions. Among
      them, 317 proteins exhibited a differential expression, compared to that of the
      controls at one time point or more. The majority of the differentially expressed
      proteins were found in the sample after a 5-h MSU treatment. Western blot
      revealed that the expression levels of cathelin-related antimicrobial peptide and
      S100A9 were positively correlated with the time-course treated with MSU. Further
      analysis of GeneGO pathway demonstrated that these differentially expressed
      proteins are primarily related to the immune-related complement system and the
      tricarboxylic acid cycle. Moreover, seven genes from the TCA cycle were found to
      be significantly downregulated at the transcriptional level and its correlation
      with gout and possible therapeutic applications are worth further investigation.
      Last, we found that pyruvate carboxylation could be potential targets for
      antigout treatment.

PMID- 26205849
TI  - Differences in defence responses of Pinus contorta and Pinus banksiana to the
      mountain pine beetle fungal associate Grosmannia clavigera are affected by water
      deficit.
AB  - We tested the hypotheses that responses to the mountain pine beetle fungal
      associate Grosmannia clavigera will differ between the evolutionarily co-evolved
      host lodgepole pine (Pinus contorta var. latifolia) and the naive host jack pine
      (Pinus banksiana) and that these responses will be influenced by water
      availability. G. clavigera inoculation resulted in more rapid stem lesion
      development in lodgepole than in jack pine; water deficit delayed lesion
      development in both species. Decreased hydraulic conductivity was observed in
      inoculated lodgepole pine seedlings, likely because of tracheid occlusion by
      fungal hyphae and/or metabolite accumulation. Drought but not inoculation
      significantly impacted bark abscisic acid levels. Jasmonic and salicylic acid
      were implicated in local and systemic responses of both species to G. clavigera,
      with salicylic acid appearing to play a greater role in jack pine response to G.
      clavigera than lodgepole pine. Water deficit increased constitutive levels and/or
      attenuated induced responses to G. clavigera for several monoterpenes in
      lodgepole but not jack pine. Instead, inoculation of well-watered but not water
      deficit jack pine resulted in a greater number of xylem resin ducts. These
      findings reveal mechanisms underlying differences in G. clavigera-induced
      responses between lodgepole and jack pine hosts, and how water availability
      modulates these responses. 

PMID- 26205850
TI  - Large-mode-area single-mode-output Neodymium-doped silicate glass all-solid
      photonic crystal fiber.
AB  - We have demonstrated a 45 MUm core diameter Neodymium-doped all-solid silicate
      glass photonic crystal fiber laser with a single mode laser output. The structure
      parameters and modes information of the fiber are both demonstrated by
      theoretical calculations using Finite Difference Time Domain (FDTD) method and
      experimental measurements. Maximum 0.8 W output power limited by launched pump
      power has been generated in 1064 nm with laser beam quality factor M(2) 1.18. 

PMID- 26205851
TI  - Alterations of Fractures in Carbonate Rocks by CO2-Acidified Brines.
AB  - Fractures in geological formations may enable migration of environmentally
      relevant fluids, as in leakage of CO2 through caprocks in geologic carbon
      sequestration. We investigated geochemically induced alterations of fracture
      geometry in Indiana Limestone specimens. Experiments were the first of their
      kind, with periodic high-resolution imaging using X-ray computed tomography (xCT)
      scanning while maintaining high pore pressure (100 bar). We studied two CO2
      acidified brines having the same pH (3.3) and comparable thermodynamic
      disequilibrium but different equilibrated pressures of CO2 (PCO2 values of 12 and
      77 bar). High-PCO2 brine has a faster calcite dissolution kinetic rate because of
      the accelerating effect of carbonic acid. Contrary to expectations, dissolution
      extents were comparable in the two experiments. However, progressive xCT images
      revealed extensive channelization for high PCO2, explained by strong positive
      feedback between ongoing flow and reaction. The pronounced channel increasingly
      directed flow to a small region of the fracture, which explains why the overall
      dissolution was lower than expected. Despite this, flow simulations revealed
      large increases in permeability in the high-PCO2 experiment. This study shows
      that the permeability evolution of dissolving fractures will be larger for faster
      reacting fluids. The overall mechanism is not because more rock dissolves, as
      would be commonly assumed, but because of accelerated fracture channelization. 

PMID- 26205853
TI  - Genome Sequence of Klebsiella pneumoniae YZUSK-4, a Bacterium Proposed as a
      Starter Culture for Fermented Meat Products.
AB  - Klebsiella pneumoniae strain YZUSK-4, isolated from Chinese RuGao ham, is an
      efficient branched-chain aminotransferase-producing bacterium that can be used
      widely in fermented meat products to enhance flavor. The draft genome sequence of
      strain YZUSK-4 may provide useful genetic information on branched-chain amino
      acid aminotransferase production and branched-chain amino acid metabolism. 

PMID- 26205852
TI  - Skeletal Effects of Smoking.
AB  - Smoking is a leading cause of preventable death and disability. Smoking has long
      been identified as a risk factor for osteoporosis, with data showing that older
      smokers have decreased bone mineral density and increased fracture risk compared
      to nonsmokers, particularly at the hip. The increase in fracture risk in smokers
      is out of proportion to the effects on bone density, indicating deficits in bone
      quality. Advanced imaging techniques have demonstrated microarchitectural
      deterioration in smokers, particularly in the trabecular compartment. The
      mechanisms by which smoking affects skeletal health remain unclear, although
      multiple pathways have been proposed. Smoking cessation may at least partially
      reverse the adverse effects of smoking on the skeleton.

PMID- 26205854
TI  - Draft Genome Sequence of the Ale-Fermenting Saccharomyces cerevisiae Strain
      GSY2239.
AB  - Saccharomyces cerevisiae strain GSY2239 is derived from an industrial yeast
      strain used to ferment ale-style beer. We present here the 11.5-Mb draft genome
      sequence for this organism. 

PMID- 26205855
TI  - Draft Genome Sequence of Lactobacillus panis DSM 6035T, First Isolated from
      Sourdough.
AB  - We report a draft genome sequence of Lactobacillus panis DSM 6035(T), isolated
      from sourdough. The genome of this strain is 2,082,789 bp long, with 47.9% G+C
      content. A total of 2,047 protein-coding genes were predicted. 

PMID- 26205856
TI  - Draft Genome Sequence of Thermophilic Exiguobacterium sp. Strain JLM-2, Isolated
      from Deep-Sea Ferromanganese Nodules.
AB  - Exiguobacterium sp. strain JLM-2 is a thermophilic bacterium isolated from deep
      sea ferromanganese (FeMn) nodules. The estimated genome of this strain is 2.9 Mb,
      with a G+C content of 48.32%. It has a novel circular 15,570-bp plasmid. The
      draft genome sequence may provide useful information about Mn-microbe
      interactions and the genetic basis for tolerance to environment stresses. 

PMID- 26205857
TI  - Draft Genome Sequence of the Cellulolytic and Xylanolytic Thermophile Clostridium
      clariflavum Strain 4-2a.
AB  - Clostridium clariflavum strain 4-2a, a novel strain isolated from a thermophilic
      biocompost pile, has demonstrated an extensive capability to utilize both
      cellulose and hemicellulose under thermophilic anaerobic conditions. Here, we
      report the draft genome of this strain. 

PMID- 26205858
TI  - Draft Genome Sequence of Burkholderia sp. Strain PML1(12), an
      Ectomycorrhizosphere-Inhabiting Bacterium with Effective Mineral-Weathering
      Ability.
AB  - We report the draft genome sequence of Burkholderia sp. PML1(12), a soil
      bacterium isolated from the Oak-Scleroderma citrinum ectomycorrhizosphere in the
      experimental forest site of Breuil-Chenue (France). 

PMID- 26205859
TI  - Genome Sequence of Geobacillus sp. Strain ZGt-1, an Antibacterial Peptide
      Producing Bacterium from Hot Springs in Jordan.
AB  - This paper reports the draft genome sequence of the firmicute Geobacillus sp.
      strain ZGt-1, an antibacterial peptide producer isolated from the Zara hot spring
      in Jordan. This study is the first report on genomic data from a thermophilic
      bacterial strain isolated in Jordan. 

PMID- 26205860
TI  - Genome Sequence of Klebsiella pneumoniae CICC10011, a Promising Strain for High
      2,3-Butanediol Production.
AB  - Klebsiella pneumoniae CICC10011, a promising 2,3-butanediol producer, has
      received much attention because of its high productivity. Here, the first draft
      genome sequence of this efficient strain may provide the genetic basis for
      further insights into the metabolic and regulatory mechanisms underlying the
      production of 2,3-butanediol at a high titer. 

PMID- 26205861
TI  - Draft Genome Sequence of Broad-Spectrum Antifungal Bacterium Burkholderia
      gladioli Strain NGJ1, Isolated from Healthy Rice Seeds.
AB  - We report here the draft genome sequence of Burkholderia gladioli strain NGJ1.
      The strain was isolated from healthy rice seeds and exhibits broad-spectrum
      antifungal activity against several agriculturally important pathogens, including
      Rhizoctonia solani, Magnaporthe oryzae, Venturia inaequalis, and Fusarium
      oxysporum. 

PMID- 26205862
TI  - Complete Genome Sequence of Escherichia coli Strain RS218 (O18:H7:K1), Associated
      with Neonatal Meningitis.
AB  - Escherichia coli RS218 is the prototypic strain of neonatal meningitis-causing E.
      coli (NMEC) and has been used in many studies related to NMEC pathogenesis. In
      the present study, the genome of E. coli RS218 was sequenced together with its
      plasmid, pRS218. Here, we report the fully closed genome sequence of E. coli
      RS218. 

PMID- 26205863
TI  - Draft Genome Sequence of Mycobacterium heraklionense Strain Davo.
AB  - We report the draft genome sequence of Mycobacterium heraklionense strain Davo,
      isolated from a fine-needle aspirate of a right-ankle soft-tissue mass. This is
      the first draft genome sequence of Mycobacterium heraklionense, a nonpigmented
      rapidly growing mycobacterium. 

PMID- 26205864
TI  - Draft Genome Sequence of Caprolactam-Degrading Pseudomonas putida Strain SJ3.
AB  - Pseudomonas putida strain SJ3, which possesses caprolactam-degrading ability, was
      isolated from dyeing industry wastewater in Daegu, Republic of Korea. Here, we
      describe the draft genome sequence and annotation of the strain. The 5,596,765-bp
      long genome contains 4,293 protein-coding genes and 68 RNA genes with 61.70% G+C
      content. 

PMID- 26205865
TI  - Draft Genome Sequence of Mycobacterium europaeum Strain CSUR P1344.
AB  - We report the draft genome sequence of Mycobacterium europaeum strain CSUR P1344,
      a slowly growing mycobacterium of the Mycobacterium simiae complex and
      opportunistic respiratory tract colonizer and pathogen. This genome of 6,152,523
      bp exhibits a 68.18% G+C content, encoding 5,814 predicted proteins and 74 RNAs. 

PMID- 26205866
TI  - Draft Genome Sequence of Mycobacterium lentiflavum CSUR P1491.
AB  - We announce the draft genome sequence of Mycobacterium lentiflavum strain CSUR
      P1491, a nontuberculous mycobacterium responsible for opportunistic potentially
      life-threatening infections in immunocompromised patients. The genome described
      here comprises a 6,818,507-bp chromosome exhibiting a 65.75% G+C content, 6,354
      protein-coding genes, and 75 RNA genes. 

PMID- 26205867
TI  - Draft Genome Sequences of Klebsiella oxytoca Isolates Originating from a Highly
      Contaminated Liquid Hand Soap Product.
AB  - In 2013, contaminated liquid soap was detected by routine microbiological
      monitoring of consumer products through state health authorities. Because of its
      high load of Klebsiella oxytoca, the liquid soap was notified via the European
      Union Rapid Alert System for Dangerous Non-Food Products (EU-RAPEX) and recalled.
      Here, we present two draft genome sequences and a summary of their general
      features. 

PMID- 26205868
TI  - Draft Genome Sequence of the Biofilm-Hyperproducing Acinetobacter baumannii
      Clinical Strain MAR002.
AB  - We report the draft genome sequence of Acinetobacter baumannii strain MAR002, a
      biofilm-hyperproducing clinical strain isolated during the study CP/09/0033
      (GEIH/REIPI-Ab2010, Spain). The genome of A. baumannii MAR002 has an approximate
      length of 3,717,929 bp and 3,300 protein-coding sequences, with a C+G content of
      39.09%. 

PMID- 26205869
TI  - Draft Genome Sequence of Strain ATCC 33958, Reported To Be Elizabethkingia
      miricola.
AB  - We report the draft genome of Elizabethkingia strain ATCC 33958, which has been
      classified as Elizabethkingia miricola. Similar to other Elizabethkingia species,
      the ATCC 33958 draft genome contains numerous beta-lactamase genes. ATCC 33958
      also harbors a urease gene cluster which supports classification as E. miricola. 

PMID- 26205870
TI  - Complete Genome Sequence of an Edwardsiella piscicida-Like Species Isolated from
      Diseased Grouper in Israel.
AB  - The Edwardsiella piscicida-like sp. is a Gram-negative facultative anaerobe that
      causes disease in some fish species. We report here the complete genome sequence
      of a virulent isolate from a diseased white grouper (Epinephelus aeneus) raised
      on the Red Sea in Israel, which contains a chromosome of 3,934,167 bp and no
      plasmids. 

PMID- 26205871
TI  - Genome Sequence of Torulaspora delbrueckii NRRL Y-50541, Isolated from Mezcal
      Fermentation.
AB  - Torulaspora delbrueckii presents metabolic features interesting for
      biotechnological applications (in the dairy and wine industries). Recently, the
      T. delbrueckii CBS 1146 genome, which has been maintained under laboratory
      conditions since 1970, was published. Thus, a genome of a new mezcal yeast was
      sequenced and characterized and showed genetic differences and a higher genome
      assembly quality, offering a better reference genome. 

PMID- 26205872
TI  - Draft Genome Sequence of Staphylococcus sciuri subsp. sciuri Strain Z8, Isolated
      from Human Skin.
AB  - Staphylococcus sciuri subsp. sciuri strain Z8 was isolated from a skin wound
      infection of a patient with infective endocarditis. To the best of our knowledge,
      the genome sequence of the species S. sciuri has not been previously studied. The
      complete genome sequence of strain Z8 includes a genome of 2,620,868 bp (32.43%
      GC content) without any plasmids. 

PMID- 26205873
TI  - Draft Genome Sequence of Escherichia coli O157:H7 ATCC 35150 and a Nalidixic Acid
      Resistant Mutant Derivative.
AB  - Shiga toxin-producing Escherichia coli strains, occasionally isolated from food,
      are of public health importance. Here, we report on the 5.30-Mbp draft genome
      sequence of E. coli O157:H7 EDL931 (strain ATCC 35150) and the 5.32-Mbp draft
      genome sequence of a nalidixic acid-resistant mutant derivative used as a
      distinguishable control strain in food-testing laboratories. 

PMID- 26205874
TI  - Genome Sequence of Brevibacillus formosus F12T for a Genome-Sequencing Project
      for Genomic Taxonomy and Phylogenomics of Bacillus-Like Bacteria.
AB  - Brevibacillus formosus F12(T) is a Gram-positive, spore-forming, and strictly
      aerobic bacterium. Here, we report the draft 6.215-Mb genome sequence of B.
      formosus F12(T), which will provide useful information for genomic taxonomy and
      phylogenomics of Bacillus-like bacteria, as well as for the functional gene
      mining and application of B. formosus. 

PMID- 26205875
TI  - Draft Genome Sequence of Environmental Bacterium Vibrio vulnificus CladeA-yb158.
AB  - We report the genome sequence of the environmental Vibrio vulnificus biotype
      1_cladeA. This draft genome of the CladeA-yb158 strain, isolated in Israel,
      represents this newly emerged clonal group that contains both clinical and
      environmental strains. 

PMID- 26205876
TI  - Complete Genome Sequence of a Field Isolate of Classical Swine Fever Virus
      Belonging to Subgenotype 2.1b from Hunan Province, China.
AB  - We report the complete genome sequence of a field isolate of classical swine
      fever virus (CSFV), Hunan 23/2013, belonging to the predominant subgenotype 2.1b.
      This strain was originally isolated from diseased pigs in Hunan Province, China.
      This report will help in understanding the molecular diversity of CSFV stains
      circulating in China and in selecting and developing a suitable vaccine candidate
      for CSF control. 

PMID- 26205877
TI  - The effect of nasal irrigation formulation on the antimicrobial activity of nasal
      secretions.
AB  - BACKGROUND: Saline-based irrigation solutions are evidence-based rhinological
      treatments; however, the formulation of these solutions could theoretically alter
      the function of innate antimicrobial peptides. The aim of this study was to
      determine if the antimicrobial activity of normal human nasal secretions in vivo
      is altered by commercially available large volume irrigation solutions. METHODS:
      Minimally manipulated sinonasal secretions were collected from patients with
      chronic rhinosinusitis (CRS; n = 10) and normal healthy volunteers (n = 20). In a
      subset of control patients (n = 10) secretions were collected prior to, and at 1
      hour, 6 hours, and 24 hours after nasal irrigation with 4 commercial irrigation
      solutions. Lysozyme and lactoferrin levels were analyzed and the antimicrobial
      activity of secretions determined using a radial diffusion assay. RESULTS: The
      antimicrobial activity of nasal secretions was reduced in CRS patients compared
      to healthy volunteers (p < 0.01), but there was no significant difference in
      antimicrobial peptide concentrations. Isotonic nasal irrigation reduced lysozyme
      and lactoferrin levels, which returned to baseline levels by 6 hours; in addition
      to a sustained decrease in antimicrobial activity before returning to baseline at
      24 hours. Low-salt solution stimulated peptide secretion by approximately 40% at
      6 hours and 24 hours, but produced a transient decrease in antimicrobial
      activity, returning to baseline levels by 6 hours. Hypertonic solution initially
      decreased lysozyme and lactoferrin levels but maintained baseline levels of
      antimicrobial activity and increased peptide secretion by approximately 30% at 24
      hours. CONCLUSION: The formulation of nasal irrigation solutions significantly
      affects the measured levels and functionality of sinonasal antimicrobial
      peptides.

PMID- 26205879
TI  - Genome-Wide Identification of MESP1 Targets Demonstrates Primary Regulation Over
      Mesendoderm Gene Activity.
AB  - MESP1 is considered the first sign of the nascent cardiac mesoderm and plays a
      critical role in the appearance of cardiac progenitors, while exhibiting a
      transient expression in the developing embryo. We profiled the transcriptome of a
      pure population of differentiating MESP1-marked cells and found that they chiefly
      contribute to the mesendoderm lineage. High-throughput sequencing of endogenous
      MESP1-bound DNA revealed that MESP1 preferentially binds to two variants of E-box
      sequences and activates critical mesendoderm modulators, including Eomes, Gata4,
      Wnt5a, Wnt5b, Mixl1, T, Gsc, and Wnt3. These mesendoderm markers were enriched in
      the MESP1 marked population before the appearance of cardiac progenitors and
      myocytes. Further, MESP1-binding is globally associated with H(3)K(27)
      acetylation, supporting a novel pivotal role of it in regulating target gene
      epigenetics. Therefore, MESP1, the pioneer cardiac factor, primarily directs the
      appearance of mesendoderm, the intermediary of the earliest progenitors of
      mesoderm and endoderm organogenesis.

PMID- 26205878
TI  - Research in progress: Medical Research Council United Kingdom Refractory Asthma
      Stratification Programme (RASP-UK).
AB  - The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel
      biomarker stratification strategies in severe asthma to improve clinical
      management and accelerate development of new therapies. Prior asthma mechanistic
      studies have not stratified on inflammatory phenotype and the understanding of
      pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is
      limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and
      examine a novel composite biomarker strategy to optimise CS dose; this will also
      address what proportion of patients with severe asthma have persistent symptoms
      without eosinophilic airways inflammation after progressive CS withdrawal. There
      will be interactive partnership with the pharmaceutical industry to facilitate
      access to stratified populations for novel therapeutic studies. 

PMID- 26205880
TI  - Desire to hasten death.

PMID- 26205881
TI  - Is 'colic' baby migraine?

PMID- 26205882
TI  - Cystic fibrosis gene therapy: the first trial.

PMID- 26205883
TI  - Immunonutrition in patients undergoing liver transplantation: Too premature to
      draw conclusions.

PMID- 26205884
TI  - Autonomic Function Tests and MIBG in Parkinson's Disease: Correlation to Disease
      Duration and Motor Symptoms.
AB  - AIMS: Disorders of the autonomic nervous system (ANS) have a variable degree of
      clinical relevance in patients with Parkinson's disease (PD). Here, we assessed
      whether subclinical autonomic dysfunction, as evaluated by a complete battery of
      autonomic function tests (AFTs), correlates with PD progression. METHODS: A
      series of 27 consecutive patients with PD underwent extensive ANS investigations
      including the head-up tilt test (HUTT), Valsalva maneuver, deep-breathing test,
      and handgrip test (HG); further, they performed 123I-meta-iodobenzylguanidine
      (MIBG) scintigraphy. RESULTS: Seven of the 27 patients showed orthostatic
      hypotension (OH) at HUTT and pathological responses to the deep-breathing and HG
      test and Valsalva maneuver. The majority of the remaining 20 patients with PD
      showed pathological responses to deep-breathing (n = 13) and/or HG (n = 11). Only
      3 of 27 suffered relevant OH. MIBG uptake of myocardium was decreased in 19
      patients with PD (H/M ratio 1.3 +/- 0.2). Prolonged clinical observation (>3
      years), persistent response to levodopa, and MIBG repetition allowed us to
      exclude negative MIBG as attributable to atypical Parkinsonism. MIBG uptake did
      not correlate with OH and other AFTs. Both HG test response and MIBG did
      correlate with the Unified Parkinson's Disease Rating Scale (UPDRS) motor score
      and disease duration. A positive correlation emerged between diastolic blood
      pressure (DBP) response to HG test and MIBG and with systolic blood pressure
      (SBP) response at tilt test. CONCLUSIONS: Our investigation suggests that ANS
      impairment affects the majority of patients with PD, even those PD patients
      showing negative MIBG, irrespective of clinical neurovegetative symptoms. The
      strict correlation that has been revealed with disease progression supports the
      routine utilization of AFTs as a reliable and inexpensive tool for monitoring
      peripheral sympathetic dysfunction in PD and optimizing therapy.

PMID- 26205885
TI  - Effect of Qing'e formula on the in vitro differentiation of bone marrow-derived
      mesenchymal stem cells from proximal femurs of postmenopausal osteoporotic mice.
AB  - BACKGROUND: Qing'e formula (QEF), prepared from an ancient Chinese recipe, was
      previously suggested to regulate bone metabolism and improve bone mineral density
      in patients with osteoporosis. To study the effects of medicated serum containing
      QEF on the in vitro differentiation of bone marrow-derived mesenchymal stem cells
      (BMSCs) isolated from the proximal femurs of postmenopausal osteoporosis (PMOP)
      mice. METHODS: Using an established mouse model of PMOP, mononuclear cells were
      isolated from the bone marrow present in the proximal femurs and cultured. PMOP
      mice were also randomly divided into four groups: the untreated group (Group A)
      and the groups treated with respectively low (Group B), medium (Group C), and
      high (Group D) concentrations of QEF. Serum was isolated from each and used to
      treat the cultured BMSCs in conjunction with recombinant human bone morphogenetic
      protein-2 (rhBMP-2). Cell morphology, proliferation rates, intracellular alkaline
      phosphatase (ALP) activity, and transforming growth factor-beta 1 (TGF-beta1)
      mRNA expression were evaluated. RESULTS: QEF-treated serum, particularly that
      containing moderate and high concentrations, appears to enhance the rhBMP-2
      mediated changes in cell morphology, proliferation, and differentiation
      (determined via the expression of TGF-beta1 mRNA and ALP activity) observed in
      the BMSCs isolated from PMOP mice. CONCLUSIONS: QEF may play a role in the
      prevention and treatment of PMOP by enhancing the activity of rhBMP-2.

PMID- 26205886
TI  - High basal Wnt signaling is further induced by PI3K/mTor inhibition but sensitive
      to cSRC inhibition in mammary carcinoma cell lines with HER2/3 overexpression.
AB  - BACKGROUND: Elevated basal, ligand-independent, Wnt signaling in some canine
      breast cancer cells is not caused by classical mutations in APC, beta-Catenin or
      GSK3beta but, at least partially, by enhanced LEF1 expression. We examined the
      expression and function of EGFR/HER-regulated pathways on the ligand-independent
      Wnt signaling. METHODS: Twelve canine mammary tumor cell lines with previously
      reported differential basal Wnt activity were used. The expression levels of
      genes related to EGF-signaling were analyzed by cluster analysis. Cell lines with
      a combined overexpression of EGF-related genes and enhanced basal Wnt activity
      were treated with PI3K/mTor or cSRC inhibitors or transfected with a construct
      expressing wild-type PTEN. Subsequently, effects were measured on Wnt activity,
      cell proliferation, gene expression and protein level. RESULTS: High basal
      Wnt/LEF1 activity was associated with overexpression of HER2/3, ID1, ID2, RAC1
      and HSP90 together with low to absent cMET and PTEN mRNA expression, suggesting a
      connection between Wnt- and HER-signaling pathways. Inhibition of the HER
      regulated PI3K/mTor pathway using the dual PI3K/mTor inhibitor BEZ235 or the mTor
      inhibitor Everolimus(r) resulted in reduced cell proliferation. In the cell line
      with high basal Wnt activity, however, an unexpected further increased Wnt
      activity was found that could be greatly reduced after inhibition of the HER
      regulated cSRC activity. Inhibition of the PI3K/mTor pathway was associated with
      enhanced expression of beta-Catenin, Axin2, MUC1, cMET, EGFR and HER2 and a
      somewhat increased beta-Catenin protein content, whereas cSRC inhibition was
      associated with slightly enhanced HER3 and SLUG mRNA expression. A high protein
      expression of HER3 was found only in a cell line with high basal Wnt activity.
      CONCLUSIONS: High basal Wnt activity in some mammary cancer cell lines is
      associated with overexpression of HER-receptor related genes and HER3 protein,
      and the absence of PTEN. Inhibition of the PI3K/mTor pathway further stimulated,
      however, canonical Wnt signaling, whereas the inhibitory effect with the cSRC
      inhibitor Src-I1 on the Wnt activity further suggested a connection between Wnt
      and HER2/3-signaling.

PMID- 26205888
TI  - IL-6 Activates PI3K and PKCzeta Signaling and Determines Cardiac Differentiation
      in Rat Embryonic H9c2 Cells.
AB  - INTRODUCTION: IL-6 influences several biological processes, including cardiac
      stem cell and cardiomyocyte physiology. Although JAK-STAT3 activation is the
      defining feature of IL-6 signaling, signaling molecules such as PI3K, PKCs, and
      ERK1/2 are also activated and elicit different responses. Moreover, most studies
      on the specific role of these signaling molecules focus on the adult heart, and
      few studies are available on the biological effects evoked by IL-6 in embryonic
      cardiomyocytes. AIM: The aim of this study was to clarify the biological response
      of embryonic heart derived cells to IL-6 by analyzing the morphological
      modifications and the signaling cascades evoked by the cytokine in H9c2 cells.
      RESULTS: IL-6 stimulation determined the terminal differentiation of H9c2 cells,
      as evidenced by the increased expression of cardiac transcription factors (NKX2.5
      and GATA4), structural proteins (alpha-myosin heavy chain and cardiac Troponin T)
      and the gap junction protein Connexin 43. This process was mediated by the rapid
      modulation of PI3K, Akt, PTEN, and PKCzeta phosphorylation levels. PI3K
      recruitment was an upstream event in the signaling cascade and when PI3K was
      inhibited, IL-6 failed to modify PKCzeta, PTEN, and Akt phosphorylation. Blocking
      PKCzeta activity affected only PTEN and Akt. Finally, the overexpression of a
      constitutively active form of PKCzeta in H9c2 cells largely mimicked the
      morphological and molecular effects evoked by IL-6. CONCLUSIONS: This study
      demonstrated that IL-6 induces the cardiac differentiation of H9c2 embryonic
      cells though a signaling cascade that involves PI3K, PTEN, and PKCzeta
      activities.

PMID- 26205889
TI  - The application of FAIMS gas analysis in medical diagnostics.
AB  - There is an ever increasing need to develop new tools to aid in the diagnosis and
      monitoring of human diseases. Such tools will ultimately reduce the cost of
      healthcare by identifying disease states more quickly and cheaply than current
      practices. One method showing promise is the analysis of gas-phase biomarkers
      from human breath, urine, sweat and stool that reflect bodily metabolism.
      Analysis of these volatiles by GC MS requires specialised infra-structure and
      staff, making it unsuitable for a clinical setting. Point of care sensor based
      technologies such as eNoses often suffer from stability and sensitivity issues.
      Field-Asymmetric Ion Mobility Spectrometry (FAIMS) has potential to fulfil this
      clinical need. In this paper we review the medical need, the technology, sampling
      methods and medical evidence thus far. We conclude with reflecting on future
      developmental steps necessary to bring the device into medical practice. 

PMID- 26205887
TI  - Heterozygote of TAP1 Codon637 decreases susceptibility to HPV infection but
      increases susceptibility to esophageal cancer among the Kazakh populations.
AB  - BACKGROUND: The role of human papillomavirus (HPV) may be involved in the
      development of esophageal cancer (EC) and the polymorphic immune response gene
      transporter associated with antigen processing (TAP) may be involved in HPV
      persistence and subsequent cancer carcinogenesis. The current study aims to
      provide association evidence for HPV with EC, to investigate TAP1 polymorphisms
      in EC and assess its association with HPV statuses and EC in Kazakhs. METHODS:
      The HPV genotypes in 361 patients with EC and 66 controls selected from Kazakh
      population were evaluated using PCR. Polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) was performed to detect two SNPs of TAP1
      in 150 cases comprised of 75 HPV(+) and 75 HPV(-) patients and 283 pure ethnic
      population of Kazakh and evaluate their associations with susceptibility to EC. A
      case-to-case comparison based on the genotyping results was conducted to address
      the function of TAP1 variants in the involvement of HPV. RESULTS: The presence of
      four HPV genotypes in EC tissues - including HPV 16, 18, 31, 45 - was
      significantly higher at 64.6 % than those in controls at 18.2 % (P < 0.001). Such
      presence was strongly associated with increased risk of EC (OR 8.196; 95 % CI
      4.280-15.964). The infection of HPV16, and multi-infection of 16 and 18
      significantly increase the risk for developing EC (OR 4.616, 95 % CI 2.099
      10.151; and OR 6.029, 95 % CI 1.395-26.057 respectively). Heterozygote of TAP1
      D637G had a significantly higher risk for developing EC (OR 1.626; 95 % CI 1.080
      2.449). The odds ratio for HPV infection was significantly lower among carriers
      of TAP1 D637G polymorphism (OR 0.281; 95 % CI 0.144-0.551). CONCLUSIONS: HPV
      infection exhibits a strong positive association with the risk of EC in Kazakhs.
      Heterozygote of TAP1 D637G decreases susceptibility to HPV infection in patients
      with EC but increases susceptibility to EC among the Kazakh populations.

PMID- 26205891
TI  - Correction: Nuclear receptor LRH-1/NR5A2 is required and targetable for liver
      endoplasmic reticulum stress resolution.

PMID- 26205890
TI  - Cost-effectiveness of vitamin D supplementation and exercise in preventing
      injurious falls among older home-dwelling women: findings from an RCT.
AB  - This study assessed the cost-effectiveness of vitamin D supplementation and
      exercise, separately and combined, in preventing medically attended injurious
      falls among older home-dwelling Finnish women. Given a willingness to pay of
      ?3,000 per injurious fall prevented, the exercise intervention had an 86 %
      probability of being cost-effective in this population. INTRODUCTION: The costs
      of falling in older persons are high, both to the individual and to society. Both
      vitamin D and exercise have been suggested to reduce the risk of falls. This
      study assessed the cost-effectiveness of vitamin D supplementation and exercise,
      separately and combined, in preventing medically attended injurious falls among
      older Finnish women. METHODS: Economic evaluation was based on the results of a
      previously published 2-year randomized controlled trial (RCT) where 409 community
      dwelling women aged 70 to 80 years were recruited into four groups: (1) no
      exercise + placebo (D-Ex-), (2) no exercise + vitamin D 800 IU/day (D+Ex-), (3)
      exercise + placebo (D-Ex+), and (4) exercise + vitamin D 800 IU/day (D+Ex+). The
      outcomes were medically attended injurious falls and fall-related health care
      utilization costs over the intervention period, the latter evaluated from a
      societal perspective based on 2011 unit costs. Incremental cost-effectiveness
      ratios (ICER) were calculated for the number of injurious falls per person-year
      prevented and uncertainty estimated using bootstrapping. RESULTS: Incidence rate
      ratios (95 % CI) for medically attended injurious falls were lower in both Ex+
      groups compared with D-Ex-: 0.46 (0.22 to 0.95) for D-Ex+, 0.38 (0.17 to 0.81)
      for D+Ex+. Step-wise calculation of ICERs resulted in exclusion of D+Ex- as more
      expensive and less effective. Recalculated ICERs were ?221 for D-Ex-, ?708 for D
      Ex+, and ?3,820 for D+Ex+; bootstrapping indicated 93 % probability that each
      injurious fall avoided by D-Ex+ per person year costs ?708. At a willingness to
      pay ?3,000 per injurious fall prevented, there was an 85.6 % chance of the
      exercise intervention being cost-effective in this population. CONCLUSIONS:
      Exercise was effective in reducing fall-related injuries among community-dwelling
      older women at a moderate cost. Vitamin D supplementation had marginal additional
      benefit. The results provide a firm basis for initiating feasible and cost
      effective exercise interventions in this population.

PMID- 26205892
TI  - Erratum: Identification and characterization of nuclear and nucleolar
      localization signals in 58-kDa microspherule protein (MSP58).

PMID- 26205893
TI  - L4bn of extra NHS funding should be allocated to patient centred reforms, IPPR
      think tank urges.

PMID- 26205894
TI  - Case report of non-healing surgical wound treated with dehydrated human amniotic
      membrane.
AB  - INTRODUCTION: Non-healing wounds can pose a medical challenge as in the case of
      vasculopathic venostasis resulting in a surgical ulcer. When traditional
      approaches to wound care fail, an amniotic patch (a dehydrated tissue allograft
      derived from human amnion) can function as a biologic scaffold to facilitate and
      enhance tissue regeneration and rehabilitation. BACKGROUND: Amniotic AlphaPatches
      contain concentrated molecules of PGE2, WNT4, and GDF-11 which have angiogenic,
      trophic, and anti-inflammatory effects on tissues that may be useful in enhancing
      wound healing. AIM-CASE REPORT: We present a case of a severe non-healing
      surgical wound in a 78-year-old male 17 days post right total knee arthroplasty.
      The full-thickness wound exhibited a mobile flap, measured 4 cm long * 3 cm wide,
      and showed undermining down to patellar tissue. We treated the wound
      conservatively for 6 weeks with no evidence of wound healing. Upon failure of the
      conservative treatment, two amniotic AlphaPatch (Amniotic Therapies, Dallas, TX,
      USA) were applied to the wound, and the wound healed completely in 10 weeks.
      METHODS: In the OR, the wound was irrigated with three liters of double
      antibiotic solution under pulse lavage. Two dry amniotic AlphaPatch (4 cm * 4 cm)
      were placed over the wound with Acticoat applied on top. RESULTS: At the two-week
      follow-up visit (following the incision and drainage of the wound dehiscence and
      application of the amniotic AlphaPatch), a central scab had formed centrally in
      the wound dehiscence area. At the four-week follow-up visit, the wound dehiscence
      area had completely scabbed over with no open areas left. At the eight-week
      follow-up visit, the scab had just fallen off, and the wound was healing well
      with immature skin representing the size of a penny. At the ten-week follow-up
      visit, the wound was completely healed. DISCUSSION/CONCLUSION: Sterile,
      dehydrated amniotic tissue AlphaPatches (containing trophic factors known to
      enhance wound healing) have proven effective in completely healing an otherwise
      non-healing wound in a 78-year-old male who failed six weeks of conservative
      wound care treatment.

PMID- 26205895
TI  - Congenital Chikungunya--A Cause of Neonatal Hyperpigmentation.
AB  - A 12-day-old neonate presented with ill-defined dark pigmentation over the
      centrofacial area with flagellate pigmentation on the trunk and patchy
      pigmentation on the extremities. The mother had a history of fever starting a
      week before delivery and continuing for 3 days in the postpartum period. Together
      these led to consideration of a possible diagnosis of congenital chikungunya,
      which was confirmed according to the immunoglobulin M antibodies to chikungunya
      in the mother and child. The rare occurrence of cutaneous pigmentation was the
      only clue to the retrospective diagnosis of neonatal chikungunya. Chikungunya is
      an emerging viral disease that can be transmitted maternally during pregnancy and
      in the peripartum period. It can be added to the list of viral infections that
      can lead to fetal demise or, when present during labor and delivery, can cause
      neonatal disease with cutaneous signs.

PMID- 26205896
TI  - Positive correlation of serum adipocyte fatty acid binding protein levels with
      carotid-femoral pulse wave velocity in geriatric population.
AB  - BACKGROUND: Adipocyte fatty acid binding protein (A-FABP) is a novel fat-derived
      circulating protein, which is independently and positively associated with
      atherosclerosis. The present study evaluated the relationship between fasting
      serum A-FABP and central arterial stiffness in geriatric adults. METHODS: Fasting
      blood samples were obtained from 87 geriatric patients and the serum A-FABP
      levels were measured using an enzyme immunoassay. Carotid-femoral pulse wave
      velocity (cfPWV) was determined using the SphygmoCor system. cfPWV values of >10
      m/s represented the high arterial stiffness group, while values <=10 m/s defined
      the low arterial stiffness group. RESULTS: High arterial stiffness group
      comprised of 42 geriatric adults (48.3%). When compared to those in the low
      arterial stiffness group, the high arterial stiffness group had a higher rate of
      diabetes mellitus (P = 0.044) and hypertension (P = 0.043). Body weight (P =
      0.027), waist circumference (P = 0.035), body mass index (P = 0.001), systolic
      blood pressure (P = 0.005), diastolic blood pressure (P = 0.045), pulse pressure
      (P = 0.038), and serum A-FABP level (P < 0.001) were also higher in the high
      arterial stiffness group than in the low arterial stiffness group. Multivariate
      logistic regression analysis of the factors significantly associated with
      arterial stiffness revealed that A-FABP (odds ratio: 1.833, 95% confidence
      interval 1.123-2.993, P = 0.015) was an independent predictor of arterial
      stiffness in geriatric adults. CONCLUSIONS: Serum A-FABP levels constitute a
      major risk factor in the development of central arterial stiffness in the
      geriatric population.

PMID- 26205897
TI  - Unicortical fixation of metacarpal fractures: is it strong enough?
AB  - Unicortical fixation has some practical and theoretical advantages over
      bicortical fixation. Questions have been raised to its adequacy for post
      operative mobilization. We hypothesized that fixation using a plate and eight
      unicortical screws would be as strong as using a plate and four bicortical
      screws. A total of 40 unicortical and 40 bicortical fixations were compared using
      a cadaveric metacarpal model. Unicortical fixation was performed using an eight
      hole parallel plate and bicortical fixation with a four-hole straight plate.
      Fixations were tested to failure using four-point bending load. The mean load to
      failure was 414 N SD 38(SE) for the unicortical group and 296 N SD 29(SE) for the
      bicortical group. Significant differences between these two constructs were
      observed. The mean stiffness of the fixation was higher for the bicortical group
      than the unicortical, although this difference did not reach significance.
      Unicortical fixation alone is sufficient to enable early post-operative
      mobilization in a live model.

PMID- 26205898
TI  - Is alcohol consumption in older adults associated with poor self-rated health?
      Cross-sectional and longitudinal analyses from the English Longitudinal Study of
      Ageing.
AB  - BACKGROUND: Increases in alcohol related mortality and morbidity have been
      reported among older people in England over the last decade. There is, however,
      evidence that drinking is protective for some health conditions. The validity of
      this evidence has been questioned due to residual confounding and selection bias.
      The aim of this study is to clarify which drinking profiles and other demographic
      characteristics are associated with poor self-rated health among a community
      based sample of older adults in England. The study also examines whether drinking
      designated as being "increasing-risk" or "higher-risk" is associated with poorer
      self-rated health. METHOD: This study used data from Wave 0, Wave 1 and Wave 5 of
      the English Longitudinal Study of Ageing [ELSA]. Logistic regression analysis,
      was used to examine the association between drinking profiles (based on quantity
      and frequency of drinking) and self-rated health, adjusting for gender, age,
      wealth, social class, education, household composition, smoking and body mass
      index [BMI]. RESULTS: Twenty percent of the sample reported drinking above the
      recommended level at wave 0. Rates of poor self-rated health were highest among
      those who had stopped drinking, followed by those who never drank. The rates of
      poor self-rated health among non-drinkers were significantly higher than the
      rates of poor self-rated health for any of the groups who reported alcohol
      consumption. In the adjusted logistic regression models there were no drinking
      profiles associated with significantly higher rates of poor self-rated health
      relative to occasional drinkers. CONCLUSIONS: Among those who drank alcohol,
      there was no evidence that any pattern of current alcohol consumption was
      associated with poor self-rated health, even after adjustment for a wide range of
      variables. The results associated with the stopped drinking profile indicate
      improvement in self-rated health can be associated with changes in drinking
      behaviour. Although several limitations of the study are noted, policy makers may
      wish to consider how these findings should be translated into drinking guidelines
      for older adults.

PMID- 26205899
TI  - Jervell and Lange-Nielsen syndrome in cochlear implanted patients: our experience
      and a review of literature.
AB  - OBJECTIVES: To share our experience in cochlear implanted patients with Jervell
      and Lange-Nielsen syndrome (JLNS), to review the literature results and to
      disclose precautions which have to be taken dealing with these patients.
      MATERIALS AND METHODS: Electrocardiograms (ECG) of 503 children with congenital
      bilateral profound hearing loss which were cochlear implanted in cochlear implant
      center of a tertiary hospital were evaluated for long QT syndrome. Clinical
      reports of the patients with JLNS were evaluated and a review of literature
      performed. RESULTS: The prevalence of disease was 0.79% (four cases) in our
      center which is in the range of literature reports (0-2.6%). None of our patients
      had a history of syncopal attack. Two patients (50%) were born from parents with
      consanguineous marriage. Considering all precautions their cochlear implant
      surgeries were done uneventfully. A review of the literature has identified
      sixteen reports on cochlear implantation in a total of 38 children with JLNS.
      Similar to our cases none of the authors reported cardiac events during device
      switch-on. Nine available reports about the outcome of cochlear implantation in
      these patients indicated good auditory outcome. CONCLUSION: It is recommended
      that all congenitally deaf patients have an ECG taken as a part of the
      evaluation. As auditory stimuli is reported to be a specific trigger, it is
      prudent to activate the processor with continuous heart monitoring even though
      there is no reported cardiac event during device switch-on. Cochlear implantation
      can be performed relatively safely in these patients if necessary precautions
      have been taken appropriately and their auditory outcome is good. Triggers of the
      cardiac events should be avoided throughout their life.

PMID- 26205900
TI  - Application of Central Composite Design in Optimization of Valsartan
      Nanosuspension to Enhance its Solubility and Stability.
AB  - The objective of the present research is to prepare stable nano suspensions of
      Valsartan (VAL) with high solubility and dissolution. VAL is an orally
      administered anti-hypertensive drug with lower bio-availability of 25%, this is
      attributed to its lower aqueous solubility (0.082 mg/ml). VAL nano suspensions
      were prepared by using a bottom-up precipitation technique using five level full
      factorial central composite design (CCD). The optimized nano formulations NS21,
      NS22, NS23 showed the particle size of 268.42+/-8.99, 288.3+/-11.32, 293.46+/
      6.92 nm, zeta potential of 20.89+/-0.79, 26.01 +/-1.02, 21.34+/-0.43 mVs and the
      dissolution efficiency of 93.10+/-1.459, 91.84+/-1.419, 89.47+/-0.644 %
      respectively. SEM & AFM studies represent the formation of fine irregularly
      shaped particles with smooth surfaces on nanosization. X-rd studies confirmed the
      physical state conversion of crystalline drug into amorphous form. Drug excipient
      compatibility was studied using differential scanning calorimetry (DSC) and
      Fourier transform infrared spectroscopy (FT-IR). The investigation pragmatic the
      solubility and dissolution efficiency of VAL in nanosuspension was significantly
      higher when compared with its pure form. Finally, it is concluded that,
      nanosuspension approach could be an ideal, promising approach to increase the
      solubility and dissolution of BCS-II drugs like Valsartan. 

PMID- 26205901
TI  - The Fate of Exogenous Human HSP70 Introduced into Animal Cells by Different
      Means.
AB  - Over the last decade, it has become evident that in mammals, including humans,
      heat shock protein 70 (HSP70), apart from its intracellular localization, is
      found in extracellular space, where it may execute various protective functions.
      Furthermore, the upregulation of HSP70 family members can be beneficial in the
      prevention and treatment of various human neurodegenerative diseases and cancer.
      Here, we demonstrate that recombinant human HSP70 after intranasal administration
      can penetrate various brain regions of mice in its native form and subsequently
      undergo rapid degradation. It was also shown that labeled HSP70 added to culture
      medium of different human and mouse cell lines enters the cells with strikingly
      different kinetics, which positively correlates with the basic levels of membrane
      bound Toll-like receptors (TLR) that are characteristic of these cell lines.
      HSP70 administration does not significantly modulate the level of TLR expression
      at the protein or RNA level. The degradation of the introduced recombinant HSP70
      after entering the cells is likely proteasome-dependent and varies significantly
      depending on the cells type and origin. These results should be considered when
      developing HSP70-based therapies. 

PMID- 26205902
TI  - Peripheral nerve catheters in children: an analysis of safety and practice
      patterns from the pediatric regional anesthesia network (PRAN).
AB  - BACKGROUND: Peripheral nerve catheters (PNCs) are used with increasing frequency
      in children. Although adult studies have demonstrated safety with this technique,
      there have been few safety studies in children. The main objective of the current
      investigation was to examine the incidence of PNC complications in children
      undergoing surgery. METHODS: This is an observational, multi-institutional study
      using the Pediatric Regional Anesthesia Network (PRAN) database. Data pertaining
      to PNCs were entered prospectively into a secure, online database by each
      participating centre. Patient characteristics, anatomic location, localization
      techniques, medications used, and complications were recorded for each catheter.
      All complications and any sequelae were followed until resolution. RESULTS: There
      were 2074 PNCs included in the study. 251 adverse events and complications were
      recorded, resulting in an overall incidence (95% CI) of complications of 12.1%
      (10.7-13.5%). The most common complications were catheter malfunction, block
      failure, infection, and vascular puncture. There were no reports of persistent
      neurologic problems, serious infection, or local anaesthetic systemic toxicity,
      resulting in an estimated incidence (95% CI) of 0.04% (0.001-0.2%). Patients who
      developed an infection had used the catheters for a greater number of days,
      median (IQR) of 4.5 (3-7) days compared with 3 (1-3) days in the patients who did
      not develop an infection, P<0.0001. CONCLUSIONS: Our data support the safety of
      placing PNCs in children, with adverse event rates similar to adult studies.
      Catheter problems are common, yet minor, in severity.

PMID- 26205904
TI  - Effect of different levels of mangosteen peel powder supplement on the
      performance of dairy cows fed concentrate containing yeast fermented cassava chip
      protein.
AB  - This study aimed to investigate the effect of mangosteen (Garcinia mangostana)
      peel powder (MSP) supplementation on feed intake, nutrient digestibility, ruminal
      fermentation, and milk production in lactating dairy cows fed a concentrate
      containing yeast fermented cassava chip protein (YEFECAP). Four crossbred dairy
      cows (50 % Holstein-Friesian and 50 % Thai native breed) in mid-lactation, 404 +/
      50.0 kg of body weight and 90 +/- 5 day in milk with daily milk production of 9
      +/- 2.0 kg/day, were randomly assigned according to a 4 * 4 Latin square design
      to receive 4 dietary treatments. The treatments were different levels of MSP
      supplementation at 0, 100, 200, and 300 g/head/day. Rice straw was used as a
      roughage source and fed ad libitum to all cows, and concentrate containing
      YEFECAP at 200 g/kg concentrate was offered corresponding to concentrate to milk
      yield ratio at 1:2. Results revealed that feed intake, apparent nutrient
      digestibility, ruminal pH and temperature, and total volatile fatty acid were not
      significantly affected by MSP supplementation (P > 0.05). However, increasing
      levels of MSP supplementation increased molar proportion of propionate while
      ammonia-nitrogen, acetate, and acetate to propionate ratio were decreased (P <
      0.01). Moreover, milk production and economic return were increased linearly (P <
      0.01) with the increasing level of MSP supplementation. The present findings
      suggested that supplementation of MSP especially at 300 g/head/day with
      concentrate containing YEFECAP at 200 g/kg could improve rumen fermentation
      efficiency, milk production and protein content, and economical return of
      lactating dairy cows fed on rice straw. 

PMID- 26205903
TI  - Baseline characteristics of the omega-3 fatty acids (Fish oils) and Aspirin in
      Vascular access OUtcomes in REnal Disease (FAVOURED) study.
AB  - AIM: The Fish oils and Aspirin in Vascular access OUtcomes in REnal Disease
      (FAVOURED) trial investigated whether 3 months of omega-3 polyunsaturated fatty
      acids, either alone or in combination with aspirin, will effectively reduce
      primary access failure of de novo arteriovenous fistulae. This report presents
      the baseline characteristics of all study participants, examines whether study
      protocol amendments successfully increased recruitment of a broader and more
      representative haemodialysis cohort, including patients already receiving
      aspirin, and contrasts Malaysian participants with those from Australia, New
      Zealand and the United Kingdom (UK). METHOD: This international, randomized,
      double-blind, placebo-controlled trial included patients older than 19 years with
      stage 4 or 5 chronic kidney disease currently receiving, or planned within 12
      months to receive haemodialysis. RESULTS: Participants (n = 568) were overweight
      (28.6 +/- 7.3 kg/m(2) ), relatively young (54.8 +/- 14.3 years), and
      predominantly male (63%) with a high prevalence of diabetes mellitus (46%) but
      low rate of ischaemic heart disease (8%). Sixty one percent were planned for
      lower arm arteriovenous fistula creation. Malaysian participants (n = 156) were
      younger (51.8 +/- 13.6 years vs 57.1 +/- 14.2 years, P < 0.001) with a higher
      prevalence of diabetes mellitus (65% vs 43%, P < 0.001), but less ischaemic heart
      disease (5% vs 14%, P < 0.01) compared with the combined Australian, New Zealand
      and UK cohort (n = 228). Protocol modifications allowing for inclusion of
      patients receiving aspirin increased the prevalence of co-morbidities compared
      with the original cohort. CONCLUSIONS: The FAVOURED study participants, while
      mostly similar to patients in contemporary national registry reports and
      comparable recent clinical trials, were on average younger and had less ischaemic
      heart disease. These differences were reduced as a consequence of including
      patients already receiving aspirin.

PMID- 26205905
TI  - Ideal proportion of roughage and concentrate for Malpura ewes to adapt and
      reproduce in a semi-arid tropical environment.
AB  - The study was designed to identify the most appropriate roughage to concentrate
      ratio for Malpura ewes under semi-arid tropical environments. The study was
      conducted for a period of 35 days and included 30 (2 years old) non-pregnant
      Malpura ewes weighing between 30 and 35 kg. Estrus synchronization was carried
      out in all the animals using indigenously developed intravaginal sponges
      impregnated with progesterone. The ewes were randomly divided into three groups
      (n = 10/group) namely R50 (n = 10; roughage to concentrate, 50:50), R60 (n = 10;
      roughage to concentrate, 60:40), and R70 (n = 10; roughage to concentrate,
      70:30). Individual feed and water intake was recorded on a daily basis throughout
      the course of the study. Growth variables, physiological responses, blood
      metabolites, and endocrine responses were estimated at weekly intervals. Results
      of the study indicated that nutritional treatment significantly influenced growth
      variables including body weight (p < 0.01), BCS (p < 0.01), feed intake (p <
      0.05), and water intake (p < 0.01) among the different treatment groups. The
      highest growth variables were recorded in R50 whereas the lowest were in R70.
      Both respiration rate (p < 0.01) and plasma estradiol levels (p < 0.05) also
      showed a similar trend as that of the growth variables. However, growth hormone
      (p < 0.01), T3 (p < 0.01), Hb (p < 0.01), glucose (p < 0.05), and estrus duration
      (p < 0.05) demonstrated a reverse trend with highest values recorded in R70 and
      lowest in R50. However, the nutritional treatment did not influence pulse rate,
      rectal temperature, T4, progesterone, PCV, total cholesterol, total protein,
      albumin, estrus%, and estrus cycle length. Since the additional concentrate
      supplementation in R50 and R60 did not improve the production variables, it can
      be concluded that providing 70 % roughage and 30 % concentrate could be a more
      appropriate and economically feasible ration composition for Malpura ewes reared
      in semi-arid tropical environments. 

PMID- 26205906
TI  - Prevalence, intensity and risk factors of infestation with major gastrointestinal
      nematodes in equines in and around Shashemane, Southern Ethiopia.
AB  - Prevalence, intensity and risk factors of major gastrointestinal nematode
      infestation in equines were studied through a cross-sectional survey in 384
      equids from October 2013 to April 2014 in and around Shashemane, southern
      Ethiopia. Three hundred and fifteen equids (82 %) were demonstrated harbouring
      one or more gastrointestinal (GIT) nematodes using the faecal flotation
      technique. The prevalence of GIT nematode infestation was 73.4, 85 and 86.5 % for
      horses, mules and donkeys, respectively. The identified nematodes were strongyle
      type (73.4 %), Parascaris equorum (21.4 %) and Oxyuris equi (4.4 %). Species of
      equines had a significant (chi (2) = 9.35, P < 0.01) association with the
      occurrence of GIT nematode infestation. Donkeys were two times (OR = 2.3, 95 % CI
      1.27-4.28, P < 0.01) more likely getting GIT nematode infestation than horses.
      Moreover, donkeys had the highest mean faecal egg counts (1831.2 egg per gram
      (EPG)) followed by mules (915.7 EPG) and horses (772.5 EPG). There was a
      significant association (P < 0.05) between mean EPG and body condition score in
      each equine species. In conclusion, this study provides information which might
      help in designing upcoming control strategies to control nematode infestation in
      equines. Moreover, suitable tropical climatic conditions, low level of management
      and owners' awareness, and poor animal health services are expected to contribute
      for high nematode infestation. Therefore, emphasis should be given to awareness
      creation about the strategic deworming, animal welfare and management. 

PMID- 26205907
TI  - Hybrid thoracoscopic epicardial and catheter-based endocardial ablation for
      atrial fibrillation.
AB  - Treatment of atrial fibrillation (AF) has evolved substantially, from open
      surgical 'cut-and-sew' procedures to catheter ablations to minimally invasive
      ablation with novel energy sources. Recurrences present a significant challenge,
      both to clinicians and to patients who seek a durable result and freedom from
      antiarrhythmic medications. Our centre performs a minimally invasive bilateral
      thoracoscopic epicardial ablation and atrial appendage exclusion, followed by a
      catheter-based endocardial electrophysiology study and ablation. Results
      demonstrate favourable outcomes with improvement over catheter-based ablation
      alone or thoracoscopic ablation alone. We will describe our surgical approach,
      mid-term results and a brief review of the literature surrounding this dual
      modality approach to AF ablation.

PMID- 26205908
TI  - Cochliobolus lunatus colonizes potato by adopting different invasion strategies
      on cultivars: New insights on temperature dependent-virulence.
AB  - Extreme temperature fluctuations affect the interaction dynamics of Cochliobolus
      lunatus through temperature-dependent virulence, virulence differentiation and
      induced-virulence which poses a major threat to global food security. The
      relationship between higher temperature and pathogenicity of C. lunatus on
      reported hosts are poorly understood. In this study, temperature stress was
      applied on C. lunatus to investigate the correlation among the different types of
      conidia. Additionally, a comparative dissection of the invasion process,
      infection structures and conidial germination pattern on four different Solanum
      tuberosum L. (potato) cultivars were performed. Based on microscopic examination,
      it was found that C. lunatus adopts different hyphae morphology and septation
      pattern at different temperature regimes and produce different types of conidia.
      The study showed that four-celled conidia are overproduced at elevated
      temperature (>30  degrees C) than one, two, three and five-celled conidia. Our
      finding revealed that C. lunatus conidia exhibit bipolar germination (>14.67%,
      P<0.05), unipolar germination (>35.33%, P<0.05), penetrate subcutaneously via
      epidermal anticlinal cell wall (>0.33%, P < 0.05) and differentially form
      appressoria-like structures during colonization of four different potato
      cultivars. Importantly, it is shown that unipolar germination and bipolar
      germination in C. lunatus are independently occurring phenomenon irrespective of
      the host. It is confirmed that C. lunatus adopt different but highly successful
      strategies on four different potato cultivars to incite brown-to-black leaf spot
      disease. Altogether, our data showed that increase in temperature enhances C.
      lunatus virulence on different potato cultivars irrespective of their inherent
      thermotolerant traits.

PMID- 26205909
TI  - Measurements of morphology and refractive indexes on human downy hairs using
      three-dimensional quantitative phase imaging.
AB  - We present optical measurements of morphology and refractive indexes (RIs) of
      human downy arm hairs using three-dimensional (3-D) quantitative phase imaging
      techniques. 3-D RI tomograms and high-resolution two-dimensional synthetic
      aperture images of individual downy arm hairs were measured using a Mach-Zehnder
      laser interferometric microscopy equipped with a two-axis galvanometer mirror.
      From the measured quantitative images, the RIs and morphological parameters of
      downy hairs were noninvasively quantified including the mean RI, volume,
      cylinder, and effective radius of individual hairs. In addition, the effects of
      hydrogen peroxide on individual downy hairs were investigated.

PMID- 26205910
TI  - Fatty acid profile of plasma NEFA does not reflect adipose tissue fatty acid
      profile.
AB  - Adipose tissue (AT) fatty acid (FA) composition partly reflects habitual dietary
      intake. Circulating NEFA are mobilised from AT and might act as a minimally
      invasive surrogate marker of AT FA profile. Agreement between twenty-eight FA in
      AT and plasma NEFA was assessed using concordance coefficients in 204 male and
      female participants in a 12-month intervention using supplements to increase the
      intake of EPA and DHA. Concordance coefficients generally showed very poor
      agreement between AT FA and plasma NEFA at baseline SFA: 0.07; MUFA: 0.03; n-6
      PUFA: 0.28; n-3 PUFA: 0.01). Participants were randomly divided into training (70
      %) and validation (30 %) data sets, and models to predict AT and dietary FA were
      fitted using data from the training set, and their predictive ability was
      assessed using data from the validation set. AT n-6 PUFA and SFA were predicted
      from plasma NEFA with moderate accuracy (mean absolute percentage error n-6 PUFA:
      11 % and SFA: 8 %), but predicted values were unable to distinguish between low,
      medium and high FA values, with only 25 % of n-6 PUFA and 33 % of SFA predicted
      values correctly assigned to the appropriate tertile group. Despite an
      association between AT and plasma NEFA EPA (P=0.001) and DHA (P=0.01) at
      baseline, there was no association after the intervention. To conclude, plasma
      NEFA are not a suitable surrogate for AT FA. 

PMID- 26205911
TI  - Hippocampal activity mediates the relationship between circadian activity rhythms
      and memory in older adults.
AB  - Older adults experience parallel changes in sleep, circadian rhythms, and
      episodic memory. These processes appear to be linked such that disruptions in
      sleep contribute to deficits in memory. Although more variability in circadian
      patterns is a common feature of aging and predicts pathology, little is known
      about how alterations in circadian activity rhythms within older adults influence
      new episodic learning. Following 10 days of recording sleep-wake patterns using
      actigraphy, healthy older adults underwent fMRI while performing an associative
      memory task. The results revealed better associative memory was related to more
      consistent circadian activity rhythms, independent of total sleep time, sleep
      efficiency, and level of physical activity. Moreover, hippocampal activity during
      successful memory retrieval events was positively correlated with associative
      memory accuracy and circadian activity rhythm (CAR) consistency. We demonstrated
      that the link between consistent rhythms and associative memory performance was
      mediated by hippocampal activity. These findings provide novel insight into how
      the circadian rhythm of sleep-wake cycles are associated with memory in older
      adults and encourage further examination of circadian activity rhythms as a
      biomarker of cognitive functioning. 

PMID- 26205912
TI  - Dexmedetomidine as an Adjuvant to Analgesic Strategy During Vaso-Occlusive
      Episodes in Adolescents with Sickle-Cell Disease.
AB  - Patients with sickle-cell disease (SCD) can experience recurrent vaso-occlusive
      episodes (VOEs), which are associated with severe pain. While opioids are the
      mainstay of analgesic therapy, in some patients with SCD, increasing opioid use
      is associated with continued and increasing pain. Dexmedetomidine, an alpha2 
      adrenoreceptor agonist with sedative and analgesic properties, has been
      increasingly used in the perioperative and intensive care settings and has been
      shown to reduce opioid requirement and to facilitate opioid weaning. Therefore,
      there might be a role for dexmedetomidine in pain management during VOEs in
      patients with SCD. Here, we present the hospital course of 3 patients who during
      the course of VOEs had severe pain unresponsive to opioids and ketamine and were
      treated with dexmedetomidine. Dexmedetomidine infusions that lasted for 3 to 6
      days were associated with marked reduction in daily oral morphine-equivalent
      intake and decreases in pain scores (numeric rating scale). There were no
      hemodynamic changes that required treatment with vasoactive or anticholinergic
      agents. These preliminary findings of possible beneficial effects of
      dexmedetomidine in decreasing opioid requirements support the hypothesis that
      dexmedetomidine may have a role as a possible analgesic adjuvant to mitigate VOE
      associated pain in patients with SCD. 

PMID- 26205913
TI  - Identifying e-cigarette vape stores: description of an online search methodology.
AB  - BACKGROUND: Although the overall impact of Electronic Nicotine Delivery Systems
      (ENDS) on public health is unclear, awareness, use, and marketing of the products
      have increased markedly in recent years. Identifying the increasing number of
      'vape stores' that specialise in selling ENDS can be challenging given the lack
      of regulatory policies and licensing. This study assesses the utility of online
      search methods in identifying ENDS vape stores. METHODS: We conducted online
      searches in Google Maps, Yelp, and YellowPages to identify listings of ENDS vape
      stores in Florida, and used a crowdsourcing platform to call and verify stores
      that primarily sold ENDS to consumers. We compared store listings generated from
      the online search and crowdsourcing methodology to list licensed tobacco and ENDS
      retailers from the Florida Department of Business and Professional Regulation.
      RESULTS: The combined results from all three online sources yielded a total of
      403 ENDS vape stores. Nearly 32.5% of these stores were on the state tobacco
      licensure list, while 67.5% were not. Accuracy of online results was highest for
      Yelp (77.6%), followed by YellowPages (77.1%) and Google (53.0%). CONCLUSIONS:
      Using the online search methodology we identified more ENDS vape stores than were
      on the state tobacco licensure list. This approach may be a promising strategy to
      identify and track the growth of ENDS vape stores over time, especially in states
      without a systematic licensing requirement for such stores.

PMID- 26205914
TI  - Coalescence.

PMID- 26205915
TI  - Case reports: Giant sialolith.

PMID- 26205916
TI  - Sialoliths and megaliths.

PMID- 26205917
TI  - Research ideas: Correlation does not imply causation.

PMID- 26205918
TI  - Oral health consequences of the crisis in Syria.

PMID- 26205919
TI  - Feature: Why am I feeling stressed?

PMID- 26205921
TI  - Dental defence body calls on government to make urgent legal reform.

PMID- 26205922
TI  - Barrier aids bone regrowth after socket grafting.

PMID- 26205923
TI  - How badly must a regulator perform before someone intervenes, asks BDA.

PMID- 26205928
TI  - Consent - a new era begins.
AB  - The law in relation to consent has changed following the handing down of the
      Supreme Court judgement in Montgomery vs Lanarkshire in March this year. Legally,
      clinicians, including dentists, must now take reasonable care to ensure that
      patients are aware of any material risks involved in a proposed treatment and of
      reasonable alternatives. This case now brings the law in relation to the
      disclosure of risks when obtaining consent to treatment in line with the guidance
      issued by regulatory bodies such as the GMC and GDC. 

PMID- 26205929
TI  - Erratum.
AB  - BDJ 2015; 218: 609-660 (Issue 11) . The following digital object identifier (DOI)
      numbers associated with articles in issue 11 were incorrect in the original issue
      as published on the 12 June 2015. We apologise for any inconvenience caused by
      this error.

PMID- 26205930
TI  - Why are vulnerable children not brought to their dental appointments?
AB  - A considerable number of children under 16 years of age, with an oral healthcare
      need, are not brought to their Barts Health Special Care Community Dental Service
      (BHSCCDS) appointments. The BHSCCDS needed to understand more about why
      parents/carers (parents) were failing to bring their children, in order to
      identify appropriate strategies to reduce the non-attendance. Thus, an audit was
      conducted to assess the number, frequency and reasons for all missed appointments
      (MA); this included feedback conversations with dental staff and parents.
      Information obtained from this cohort of high-risk children's families through
      personal, respectful and supportive contact improved understanding of the
      parents' individual and collective issues and lead to recommendations that could
      reduce the number of MA in the future. 

PMID- 26205934
TI  - The quality of radiographs accompanying endodontic referrals to a health
      authority clinic.
AB  - AIM: To assess the quality of radiographs accompanying endodontic referrals, from
      general dental practitioners, to a health authority clinic. METHODS: A total of
      200 conventional film and digital radiographs accompanying referrals were
      assessed and rated as 'excellent', 'diagnostically acceptable' or 'unacceptable'
      according to the National Radiographic Protection Board (NRPB) guidelines.
      Statistical analyses of the results included inter- and intra-observer agreement
      to achieve a kappa score and the chi-squared test. RESULTS: Out of the 200
      radiographs assessed, 38 (19%) were conventional film and 162 (81%) were digital.
      Of the conventional film radiographs, 55% were rated 'excellent' and 37% were
      'diagnostically acceptable', whilst 27% of digital radiographs were rated
      'excellent' and 40% were 'diagnostically acceptable'. In the 'unacceptable'
      category, 33% were digital and 8% were conventional film radiographs (p <0.001).
      CONCLUSIONS: The quality of digital radiographs was significantly lower compared
      with conventional film radiographs. The percentage of 'unacceptable' digital
      radiographs was above the target according to the NRPB guidelines. Hence, there
      is a need for improvement in quality to avoid repeat radiographs and unnecessary
      ionising radiation exposure. Instead of hard, printed copies, digital radiographs
      accompanying referrals should, within the parameters of information governance,
      be supplied electronically so that they may be optimised, if necessary, for
      better diagnostic value.

PMID- 26205935
TI  - Twitter: a viable medium for daily pain diaries in chronic orofacial pain?
AB  - OBJECTIVE: The aim of this study was to find out if Twitter could be used in a
      research context as a ubiquitous piece of software to record daily pain. DESIGN:
      This study was a feasibility study conducted electronically. SETTING: Our
      research was conducted on Twitter in 2014. SUBJECTS AND METHODS: Participants
      were recruited via electronic advertising and consented electronically to
      participate. At three time-points on two non-sequential days participants were
      asked to record pain, mood and impact ratings on a numerical scale (0-10). Data
      were extracted manually. RESULTS: Thirty-five individuals consented to
      participate. Of the 24 participants providing data, 16 provided enough data to be
      analysed. The majority of participants were female. The mean age was 44.9 (+/-
      0.78) years and the most common diagnosis for participants was Trigeminal
      Neuralgia. Participants lived in the UK, USA, Canada and New Zealand. An increase
      in mean pain was reported over consecutive time periods on both days while mood
      and impact patterns varied between days. CONCLUSION: Our study highlighted that
      participants can be recruited solely via social media and has ascertained the
      ease in which data can be collected without technical expertise. To achieve
      greater participation, differing advertisement strategies should be explored.

PMID- 26205936
TI  - Discover Dentistry: encouraging wider participation in dentistry using a massive
      open online course (MOOC).
AB  - This paper describes how a relatively new style of online learning, a massive
      open online course (MOOC), may be used to raise aspirations and widen
      participation in dental professions. A MOOC was designed and run with the aim of
      engaging prospective students of dental professions in learning and discussion.
      Over 4,200 learners signed up, and 450 students fully completed this first run of
      the course. The course attracted a significantly younger demographic than is
      typical for MOOCs, and nearly a third who responded to the pre-course survey
      reported they were doing the course specifically as preparation for a dental
      degree. The approach also provided a platform for public engagement on the
      subject of dentistry with participants, both dental professionals and members of
      the public, contributing to discussion around the learning materials from around
      the world, providing a unique, internationalised perspective of oral healthcare
      for learners. This study shows that there is genuine potential for MOOCs to
      involve people from disadvantaged backgrounds in higher education by offering
      free, accessible, enjoyable and engaging educational experiences. The data gives
      us cautious optimism that these courses can play a significant role within a
      platform of other WP interventions. 

PMID- 26205937
TI  - The letter from California--the Healthcare Reform Act and its dental
      implications.
AB  - The Patient Protection and Affordable Care Act, or Obamacare, is now providing
      medical and dental insurance for millions of Americans who never had it before
      and will bring real benefits to the American healthcare system over the next few
      years. This article discusses its provisions and shows how dentistry fits in. 

PMID- 26205948
TI  - Schistosomicidal, hepatoprotective and antioxidant activities of the methanolic
      fraction from Clerodendrum umbellatum Poir leaves aqueous extract in Schistosoma
      mansoni infection in mice.
AB  - BACKGROUND: The intensive use of Praziquantel for the treatment of
      schistosomiasis has raised concerns about the possible emergence of drug
      resistant schistosomes. As drug treatment is an important feature of schistosome
      control programs, the search for alternative drugs is therefore a priority. The
      aim of this study was to assess the schistosomicidal, hepatoprotective and
      antioxidant activities of the methanolic fraction from Clerodendrum umbellatum
      Poir leaves aqueous extract. METHODS: A phytochemical screening of the fraction
      of C. umbellatum was conducted. The fraction was administered orally and daily to
      Schistosoma mansoni-infected mice (BALB/c) from the 36th day post-infection for
      28 days at 100, 200 and 400 mg/kg. Praziquantel (500 mg/kg) was used as reference
      drug. Non-infected and infected-untreated mice served as controls. All mice were
      sacrificed at 65th day post-infection. Body weight, liver/body and spleen/body
      weights, as well as worm burden, fecal egg count, liver and intestine egg load
      were determined. In the plasma, levels of total protein, transaminases (ALT,
      AST), alkaline phosphatase and total bilirubin were monitored to assess the
      possibility of liver damage. Malondialdehyde (MDA), catalase (CAT) and
      glutathione (GSH) levels were measured in the liver as biomarkers of the
      oxidative stress. RESULTS: The phytochemical analysis of the fraction from C.
      umbellatum aqueous leaves extract revealed the presence of alkaloids, flavonoids,
      cardiac glycosides, phenols, saponins, tannins and terpenoids. The worm burden,
      fecal egg count and egg load in the liver and intestine of infected mice treated
      with the fraction were significantly (p < 0.001) fewer than in infected-untreated
      mice. Only the highest-fraction dose reduced the worm and egg burdens in a
      similar way as praziquantel. Hepatosplenomegaly induced by S. mansoni infection
      was reduced by the treatment. The liver function on infected mice was ameliorate
      after administration of the fraction by significant reduction of ALT activity
      (35.43 to 45.25%) and increase of total protein level (44.79 to 70.03%). The
      methanolic fraction of C. umbellatum prevents the elevated MDA level induced by
      the infection while significant increase in catalase activity (297.09 to 438.98%)
      and glutathione level (58.23 to 95.88%) were observed after treatment.
      CONCLUSIONS: This study disclosed the schistosomicidal, hepatoprotective and
      antioxidant activities of the methanolic fraction from C. umbellatum leaves
      aqueous. These fraction's activities were similar to those of praziquantel. This
      fraction can be considered as a promising source for schistosomicidal agents.

PMID- 26205949
TI  - Vitamin D3 enhances the tumouricidal effects of 5-Fluorouracil through
      multipathway mechanisms in azoxymethane rat model of colon cancer.
AB  - BACKGROUND: Vitamin D3 and its analogues have recently been shown to enhance the
      anti-tumour effects of 5- Fluorouracil (5-FU) both in vitro and in xenograft
      mouse model of colon cancer. This study measured the potential mechanism(s) by
      which vitamin D3 could synergise the tumouricidal activities of 5-FU in
      azoxymethane (AOM) rat model of colon cancer. METHODS: Seventy-five male Wistar
      rats were divided equally into 5 groups: Control, AOM, AOM-treated by 5-FU (5
      FU), AOM-treated by vitamin D3 (VitD3), and AOM-treated by 5-FU + vitamin D3 (5
      FU/D). The study duration was 15 weeks. AOM was injected subcutaneously for 2
      weeks (15 mg/kg/week). 5-FU was injected intraperitoneally in the 9th and 10th
      weeks post AOM (8 total injections were given: 12 mg/kg/day for 4 successive
      days, then 6 mg/kg every other day for another 4 doses) and oral vitamin D3 (500
      IU/rat/day; 3 days/week) was given from week 7 post AOM till the last week of the
      study. The colons were collected following euthanasia for gross and
      histopathological examination. The expression of beta-catenin, transforming
      growth factor-beta1 (TGF-beta1), TGF-beta type 2 receptor (TGF-betaR2), smad4,
      inducible nitric oxide synthase (iNOS), and heat shock protein-90 (HSP-90)
      proteins was measured by immunohistochemistry. In colonic tissue homogenates,
      quantitative RT-PCR was used to measure the mRNA expression of Wnt, beta-catenin,
      Dickkopf-1 (DKK-1) and cyclooxygenase-2 (COX-2) genes, while ELISA was used to
      measure the concentrations of TGF-beta1, HSP-90 and COX-2 proteins. RESULTS:
      Monotherapy with 5-FU or vitamin D3 significantly decreased the number of grown
      tumours induced by AOM (P < 0.05); however, their combination resulted in more
      significant tumouricidal effects (P < 0.05) compared with monotherapy groups.
      Mechanistically, vitamin D3/5-FU co-therapy significantly decreased the
      expression of Wnt, beta-catenin, iNOS, COX-2 and HSP-90 and significantly
      increased the expression of DKK-1, TGF-beta1, TGF-betaR2, smad4 (P < 0.05), in
      comparison with their corresponding monotherapy groups. CONCLUSIONS: Vitamin D3
      and 5-FU synergise together and exhibit better anticancer effects by modulating
      Wnt/beta-catenin pathway, TGF-beta1 signals, iNOS, COX-2 and HSP-90. Further
      studies are required to illustrate the clinical value of vitamin D
      supplementation during the treatment of colon cancer with 5-FU in human patients.

PMID- 26205951
TI  - Radioprotective potential of melatonin against 60Co gamma-ray-induced testicular
      injury in male C57BL/6 mice.
AB  - BACKGROUND: Melatonin, the chief secretary product of pineal gland, is a strong
      free radical scavenger and antioxidant molecule. The radioprotective efficacy and
      underlying mechanisms refer to its antioxidant role in somatic cells. The purpose
      of this study, therefore, was to investigate the prophylactic implications of
      melatonin against gamma-ray-induced injury in germinal cells (testes). C57BL/6
      male mice were administered melatonin (100 mg/kg) intra-peritoneally 30 min prior
      to a single dose of whole-body gamma-irradiation (5 Gy, 1 Gy/minute) using (60)Co
      teletherapy unit. Animals were sacrificed at 2h, 4h and 8h post-irradiation and
      their testes along with its spermatozoa taken out and used for total antioxidant
      capacity (TAC), lipid peroxidation, comet assay, western blotting and sperm
      motility and viability. In another set of experiment, animals were similarly
      treated were sacrificed on 1(st), 3(rd), 7(th), 15(th) and 30(th) day post
      irradiation and evaluated for sperm abnormalities and histopathological analysis.
      RESULTS: Whole-body gamma-radiation exposure (5 Gy) drastically depleted the
      populations of spermatogenic cells in seminiferous tubules on day three, which
      were significantly protected by melatonin. In addition, radiation-induced sperm
      abnormalities, motility and viability in cauda-epididymes were significantly
      reduced by melatonin. Melatonin pre-treatment significantly inhibited radiation
      induced DNA strands breaks and lipid peroxidation. At this time, radiation
      induces activation of ATM-dependent p53 apoptotic proteins-ATM, p53, p21, Bax,
      cytochrome C, active caspase-3 and caspases-9 expression, which were
      significantly reversed in melatonin pre-treated mice. This reduced apoptotic
      proteins by melatonin pre-treatment was associated with the increase of anti
      apoptotic-Bcl-x and DNA repair-PCNA proteins in irradiated mice. Further,
      radiation-induced decline in the TAC was significantly reversed in melatonin pre
      treated mice. CONCLUSIONS: The present results indicated that melatonin as
      prophylactic agent protected male reproductive system against radiation-induced
      injury in mice. The detailed study will benefit in understanding the role of
      melatonin in modulation of radiation-induced ATM-dependent p53-mediated pro-vs.
      anti apoptotic proteins in testicular injury. These results can be further
      exploited for use of melatonin for protection of male reproductive system in
      radiotherapy applications involving hemibody abdominal exposures.

PMID- 26205950
TI  - Calcium response of KCl-excited populations of ventricular myocytes from the
      European sea bass (Dicentrarchus labrax): a promising approach to integrate cell
      to-cell heterogeneity in studying the cellular basis of fish cardiac performance.
AB  - Climate change challenges the capacity of fishes to thrive in their habitat.
      However, through phenotypic diversity, they demonstrate remarkable resilience to
      deteriorating conditions. In fish populations, inter-individual variation in a
      number of fitness-determining physiological traits, including cardiac
      performance, is classically observed. Information about the cellular bases of
      inter-individual variability in cardiac performance is scarce including the
      possible contribution of excitation-contraction (EC) coupling. This study aimed
      at providing insight into EC coupling-related Ca(2+) response and thermal
      plasticity in the European sea bass (Dicentrarchus labrax). A cell population
      approach was used to lay the methodological basis for identifying the cellular
      determinants of cardiac performance. Fish were acclimated at 12 and 22  degrees C
      and changes in intracellular calcium concentration ([Ca(2+)]i) following KCl
      stimulation were measured using Fura-2, at 12 or 22  degrees C-test. The increase
      in [Ca(2+)]i resulted primarily from extracellular Ca(2+) entry but sarcoplasmic
      reticulum stores were also shown to be involved. As previously reported in sea
      bass, a modest effect of adrenaline was observed. Moreover, although the response
      appeared relatively insensitive to an acute temperature change, a difference in
      Ca(2+) response was observed between 12- and 22  degrees C-acclimated fish. In
      particular, a greater increase in [Ca(2+)]i at a high level of adrenaline was
      observed in 22  degrees C-acclimated fish that may be related to an improved
      efficiency of adrenaline under these conditions. In conclusion, this method
      allows a rapid screening of cellular characteristics. It represents a promising
      tool to identify the cellular determinants of inter-individual variability in
      fishes' capacity for environmental adaptation. 

PMID- 26205953
TI  - 21st century cures: is US medicines bill a colossal mistake?

PMID- 26205952
TI  - EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in
      melanoma.
AB  - PURPOSE: Sentinel lymph node biopsy is an essential staging tool in patients with
      clinically localized melanoma. The harvesting of a sentinel lymph node entails a
      sequence of procedures with participation of specialists in nuclear medicine,
      radiology, surgery and pathology. The aim of this document is to provide
      guidelines for nuclear medicine physicians performing lymphoscintigraphy for
      sentinel lymph node detection in patients with melanoma. METHODS: These practice
      guidelines were written and have been approved by the European Association of
      Nuclear Medicine (EANM) to promote high-quality lymphoscintigraphy. The final
      result has been discussed by distinguished experts from the EANM Oncology
      Committee, national nuclear medicine societies, the European Society of Surgical
      Oncology (ESSO) and the European Association for Research and Treatment of Cancer
      (EORTC) melanoma group. The document has been endorsed by the Society of Nuclear
      Medicine and Molecular Imaging (SNMMI). CONCLUSION: The present practice
      guidelines will help nuclear medicine practitioners play their essential role in
      providing high-quality lymphatic mapping for the care of melanoma patients.

PMID- 26205954
TI  - Is cryoablation really more effective than radiofrequency ablation in
      hepatocellular carcinoma?

PMID- 26205955
TI  - Early increase in circulating carbonic anhydrase IX during neoadjuvant treatment
      predicts favourable outcome in locally advanced rectal cancer.
AB  - BACKGROUND: Locally advanced rectal cancer (LARC) comprises heterogeneous tumours
      with predominant hypoxic components. The hypoxia-inducible metabolic shift causes
      microenvironmental acidification generated by carbonic anhydrase IX (CAIX) and
      facilitates metastatic progression, the dominant cause of failure in LARC.
      METHODS: Using a commercially available immunoassay, circulating CAIX was
      assessed in prospectively archived serial serum samples collected during combined
      modality neoadjuvant treatment of LARC patients and correlated to histologic
      tumour response and progression-free survival (PFS). RESULTS: Patients who from
      their individual baseline level displayed serum CAIX increase above a threshold
      of 224 pg/ml (with 96 % specificity and 39 % sensitivity) after completion of
      short-course neoadjuvant chemotherapy (NACT) prior to long-course
      chemoradiotherapy and definitive surgery had significantly better 5-year PFS (94
      %) than patients with below-threshold post-NACT versus baseline alteration (PFS
      rate of 56 %; p < 0.01). This particular CAIX parameter, DeltaNACT, was
      significantly correlated with histologic ypT0-2 and ypN0 outcome (p < 0.01) and
      remained an independent PFS predictor in multivariate analysis wherein it was
      entered as continuous variable (p = 0.04). CONCLUSIONS: Our results indicate that
      low DeltaNACT, i.e., a weak increase in serum CAIX level following initial
      neoadjuvant treatment (in this case two cycles of the Nordic FLOX regimen), might
      be used as risk-adapted stratification to postoperative therapy or other modes of
      intensification of the combined-modality protocol in LARC. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00278694.

PMID- 26205956
TI  - Physiological characteristics and related gene expression of after-ripening on
      seed dormancy release in rice.
AB  - After-ripening is a common method used for dormancy release in rice. In this
      study, the rice variety Jiucaiqing (Oryza sativa L. subsp. japonica) was used to
      determine dormancy release following different after-ripening times (1, 2 and 3
      months). Germination speed, germination percentage and seedling emergence
      increased with after-ripening; more than 95% germination and 85% seedling
      emergence were observed following 1 month of after-ripening within 10 days of
      imbibition, compared with <45% germination and 20% seedling emergence in freshly
      harvested seed. Hence, 3 months of after-ripening could be considered a suitable
      treatment period for rice dormancy release. Dormancy release by after-ripening is
      mainly correlated with a rapid decline in ABA content and increase in IAA content
      during imbibition. Subsequently, GA(1)/ABA, GA(7)/ABA, GA(12)/ABA, GA(20)/ABA and
      IAA/ABA ratios significantly increased, while GA(3)/ABA, GA(4)/ABA and GAs/IAA
      ratio significantly decreased in imbibed seeds following 3 months of after
      ripening, thereby altering alpha-amylase activity during seed germination. Peak
      alpha-amylase activity occurred at an earlier germination stage in after-ripened
      seeds than in freshly harvested seeds. Expression of ABA, GA and IAA metabolism
      genes and dormancy-related genes was regulated by after-ripening time upon
      imbibition. Expression of OsCYP707A5, OsGA2ox1, OsGA2ox2, OsGA2ox3, OsILR1, OsGH3
      2, qLTG3-1 and OsVP1 increased, while expression of Sdr4 decreased in imbibed
      seeds following 3 months of after-ripening. Dormancy release through after
      ripening might be involved in weakening tissues covering the embryo via qLTG3-1
      and decreased ABA signalling and sensitivity via Sdr4 and OsVP1.

PMID- 26205957
TI  - The everyday use of assistive technology by people with dementia and their family
      carers: a qualitative study.
AB  - BACKGROUND: Assistive Technology (AT) has been suggested as a means by which
      people with dementia can be helped to live independently, while also leading to
      greater efficiencies in care. However little is known about how AT is being used
      by people with dementia and their carers in their daily routines. This paper
      reports on a qualitative study exploring the everyday use of AT by people with
      dementia and their families. METHODS: The research employed a qualitative
      methodology. Semi structured interviews took place with 39 participants, 13
      people with dementia and 26 carers. Key themes were identified using thematic
      analysis and the constant comparative method. RESULTS: Three categories of AT use
      in everyday settings were identified; formal AT, accessed via social care
      services, 'off the shelf AT' purchased privately, and 'do it yourself' AT,
      everyday household products adapted by families to fulfil individual need in the
      absence of specific devices. Access to AT was driven by carers, with the majority
      of benefits being experienced by carers. Barriers to use included perceptions
      about AT cost; dilemmas about the best time to use AT; and a lack of information
      and support from formal health and social care services about how to access AT,
      where to source it and when and how it can be used. CONCLUSIONS: It has been
      argued that the 'mixed economy' landscape, with private AT provision
      supplementing state provision of AT, is a key feature for the mainstreaming of AT
      services. Our data suggests that such a mixed economy is indeed taking place,
      with more participants using 'off the shelf' and 'DIY' AT purchased privately
      rather than via health and social care services. However this system has largely
      arisen due to an inability of formal care services to meet client needs. Such
      findings therefore raise questions about just who AT in its current provision is
      working for and whether a mixed market approach is the most appropriate provider
      model. Everyday technologies play an important role in supporting families with
      dementia to continue caring; further research is needed however to determine the
      most effective and person-centred models for future AT provision.

PMID- 26205958
TI  - Acceptability of delivery modes for lifestyle advice in a large scale randomised
      controlled obesity prevention trial.
AB  - BACKGROUND: Preventing obesity is an international health priority and women
      living in rural communities are at an increased risk of weight gain. Lifestyle
      programs are needed as part of a comprehensive approach to prevent obesity.
      Evaluation provides a unique opportunity to investigate and inform improvements
      in lifestyle program implementation strategies. The Healthy Lifestyle Program for
      rural women (HeLP-her Rural) is a large scale, cluster randomized control trial,
      targeting the prevention of weight gain. This program utilises multiple delivery
      modes for simple lifestyle advice (group sessions, phone coaching, text messages,
      and an interactive program manual). Here, we describe the acceptability of these
      various delivery modes. METHODS: A mixed-method process evaluation was undertaken
      measuring program fidelity, recruitment strategies, dose delivered, program
      acceptability and contextual factors influencing program implementation. Data
      collection methodologies included qualitative semi-structured interviews for a
      sub-group of intervention participants [n = 28] via thematic analysis and
      quantitative methods (program checklists and questionnaires [n = 190]) analysed
      via chi square and t-tests. RESULTS: We recruited 649 women from 41 rural
      townships into the HeLP-her Rural program with high levels of program fidelity,
      dose delivered and acceptability. Participants were from low socioeconomic
      townships and no differences were detected between socioeconomic characteristics
      and the number of participants recruited across the towns (p = 0.15). A face-to
      face group session was the most commonly reported preferred delivery mode for
      receiving lifestyle advice, followed by text messages and phone coaching.
      Multiple sub-themes emerged to support the value of group sessions which
      included: promoting of a sense of belonging, mutual support and a forum to share
      ideas. The value of various delivery modes was influenced by participant's
      various needs and learning styles. CONCLUSION: This comprehensive evaluation
      reveals strong implementation fidelity and high levels of dose delivery. We
      demonstrate reach to women from relatively low income rural townships and
      highlight the acceptability of low intensity healthy lifestyle programs with
      mixed face-to-face and remote delivery modes in this population. Group education
      sessions were the most highly valued component of the intervention, with at least
      one face-to-face session critical to successful program implementation. However,
      lifestyle advice via multiple delivery modes is recommended to optimise program
      acceptability and ultimately effectiveness. TRIAL REGISTRY: Australia & New
      Zealand Clinical Trial Registry. Trial number ACTRN12612000115831, date of
      registration 24/01/2012.

PMID- 26205959
TI  - alpha-Glucosidase activity of oleanolic acid and its oxidative metabolites: DFT
      and Docking studies.
AB  - A natural pentacyclic triterpenoid oleanolic acid 1 and its biotransformed
      metabolites 2-3 are potential alpha-glucosidase inhibitors. To elucidate the
      inhibitory mechanism of compounds 1, 2 and 3 against alpha-glucosidase, we
      calculated (i) their electronic and optical properties using DFT and TD-DFT at
      the B3LYP/6-31G(d) level in gas and IEF-PCM solvent; and (ii) their binding
      energies to alpha-glucosidase via docking study. DFT results showed that the
      alpha-glucosidase inhibtion is mainly depend on the polarity parameters of the
      studied compounds. Docking results revealed that the activity increased with
      binding energies (i.e. the stability of ligand-receptor complex). The
      specroscopic data of oleanolic acid 1 and its metabolites 2 and 3 are well
      predicetd for 13C NMR chemical shifts (R2=99%) and 1H NMR chemical shifts
      (R2=90%); and for (ii) UV/vis spectra. The assignments and interpretation of NMR
      chemical shifts and bathochromic shift of lambdaMAX absorption bands are
      discussed. 

PMID- 26205960
TI  - Cyclic GMP in Vascular Relaxation: Export Is of Similar Importance as
      Degradation.
AB  - OBJECTIVE: In the vascular system, cyclic GMP (cGMP) in smooth muscle cells plays
      an important role for blood vessel relaxation. Intracellular concentrations of
      cGMP are thought to be determined by the action of cGMP-generating guanylyl
      cyclases (sensitive to nitric oxide or natriuretic peptides) and cGMP-degrading
      phosphodiesterases (PDE1, PDE3, and PDE5). Because functionally relevant cGMP
      elevations are not accessible to conventional methods, we applied real-time
      imaging with a fluorescence resonance energy transfer (FRET)-based cGMP indicator
      to follow nitric oxide- and natriuretic peptide-induced cGMP signals in living
      smooth muscle cells and analyzed the contribution of the miscellaneous cGMP
      generating and cGMP-degrading enzymes. APPROACH AND RESULTS: By comparison of
      cGMP signals in living smooth muscle cells and vascular relaxation of aortic
      strips in organ bath experiments, we show for the first time that FRET-based cGMP
      indicators permit the measurement of functionally relevant cGMP signals. PDE5 was
      the major cGMP phosphodiesterase responsible for reducing nitric oxide- and
      natriuretic peptide-induced cGMP signals. In contrast, PDE3-involved in the
      degradation of lower cGMP concentrations-displayed a preference for natriuretic
      peptide-stimulated cGMP. Unexpectedly, we found that cGMP is transported out of
      the cells by the ABC transporter multidrug resistance-associated protein 4 and
      this export turned out to be of similar importance for intracellular cGMP signals
      as degradation by PDE5. Functionally, inhibition of cGMP export enhanced vascular
      relaxation as much as inhibition of PDE5. CONCLUSIONS: The findings indicate that
      cGMP export out of smooth muscle cells is a key player in the regulation of
      smooth muscle cGMP signals and blood vessel relaxation.

PMID- 26205961
TI  - Polarity Protein Scrib Facilitates Endothelial Inflammatory Signaling.
AB  - OBJECTIVE: The polarity protein Scrib is highly expressed in endothelial cells
      and is required for planar cell polarity. Scrib also facilitates recycling of
      integrin alpha5 to the plasma membrane. Because integrin alpha5 signals the
      presence of the inflammatory matrix protein fibronectin, we hypothesized that
      Scrib contributes to endothelial inflammatory signaling. APPROACH AND RESULTS:
      Cytokine treatment of human umbilical vein endothelial cells induced an
      inflammatory response as evident by the induction of vascular cell adhesion
      molecule-1 (VCAM-1). Downregulation of Scrib greatly attenuated this effect. In
      endothelial-specific conditional Scrib knockout mice, in vivo lipopolysaccharide
      treatment resulted in an impaired VCAM-1 induction. These effects were
      functionally relevant because Scrib small interfering RNAs in human umbilical
      vein endothelial cells attenuated the VCAM-1-mediated leukocyte adhesion in
      response to tumor necrosis factor-alpha. In vivo, tamoxifen-induced endothelial
      specific deletion of Scrib resulted in a reduced VCAM-1-mediated leukocyte
      adhesion in response to tumor necrosis factor-alpha in the mouse cremaster model.
      This effect was specific for Scrib and not mediated by other polarity proteins.
      Moreover, it did not involve integrin alpha5 or classic pathways supporting
      inflammatory signaling, such as nuclear factor kappa light chain enhancer of
      activated B-cells or MAP kinases. Co-immunoprecipitation/mass spectrometry
      identified the zinc finger transcription factor GATA-like protein-1 as a novel
      Scrib interacting protein. Small interfering RNA depletion of GATA-like protein-1
      decreased the tumor necrosis factor-alpha-stimulated VCAM-1 induction to a
      similar extent as loss of Scrib did. Silencing of Scrib reduced GATA-like protein
      1 protein, but not mRNA abundance. CONCLUSIONS: Scrib is a novel proinflammatory
      regulator in endothelial cells, which maintains the protein expression of GATA
      like protein-1.

PMID- 26205962
TI  - Effect of CRM team leader training on team performance and leadership behavior in
      simulated cardiac arrest scenarios: a prospective, randomized, controlled study.
AB  - BACKGROUND: Effective team leadership in cardiopulmonary resuscitation (CPR) is
      well recognized as a crucial factor influencing performance. Generally,
      leadership training focuses on task requirements for leading as well as non
      leading team members. We provided crisis resource management (CRM) training only
      for designated team leaders of advanced life support (ALS) trained teams. This
      study assessed the impact of the CRM team leader training on CPR performance and
      team leader verbalization. METHODS: Forty-five teams of four members each were
      randomly assigned to one of two study groups: CRM team leader training (CRM-TL)
      and additional ALS-training (ALS add-on). After an initial lecture and three ALS
      skill training tutorials (basic life support, airway management and rhythm
      recognition/defibrillation) of 90-min each, one member of each team was randomly
      assigned to act as the team leader in the upcoming CPR simulation. Team leaders
      of the CRM-TL groups attended a 90-min CRM-TL training. All other participants
      received an additional 90-min ALS skill training. A simulated CPR scenario was
      videotaped and analyzed regarding no-flow time (NFT) percentage, adherence to the
      European Resuscitation Council 2010 ALS algorithm (ADH), and type and rate of
      team leader verbalizations (TLV). RESULTS: CRM-TL teams showed shorter, albeit
      statistically insignificant, NFT rates compared to ALS-Add teams (mean difference
      1.34 (95% CI -2.5, 5.2), p = 0.48). ADH scores in the CRM-TL group were
      significantly higher (difference -6.4 (95% CI -10.3, -2.4), p = 0.002).
      Significantly higher TLV proportions were found for the CRM-TL group: direct
      orders (difference -1.82 (95% CI -2.4, -1.2), p < 0.001); undirected orders
      (difference -1.82 (95% CI -2.8, -0.9), p < 0.001); planning (difference -0.27
      (95% CI -0.5, -0.05) p = 0.018) and task assignments (difference -0.09 (95% CI 
      0.2, -0.01), p = 0.023). CONCLUSION: Training only the designated team leaders in
      CRM improves performance of the entire team, in particular guideline adherence
      and team leader behavior. Emphasis on training of team leader behavior appears to
      be beneficial in resuscitation and emergency medical course performance.

PMID- 26205963
TI  - Creativity and Memory: Effects of an Episodic-Specificity Induction on Divergent
      Thinking.
AB  - People produce more episodic details when imagining future events and solving
      means-end problems after receiving an episodic-specificity induction-brief
      training in recollecting details of a recent event-than after receiving a control
      induction not focused on episodic retrieval. Here we show for the first time that
      an episodic-specificity induction also enhances divergent creative thinking. In
      Experiment 1, participants exhibited a selective boost on a divergent-thinking
      task (generating unusual uses of common objects) after a specificity induction
      compared with a control induction; by contrast, performance following the two
      inductions was similar on an object association task thought to involve little
      divergent thinking. In Experiment 2, we replicated the specificity-induction
      effect on divergent thinking using a different control induction, and also found
      that participants performed similarly on a convergent-thinking task following the
      two inductions. These experiments provide novel evidence that episodic memory is
      involved in divergent creative thinking. 

PMID- 26205964
TI  - Human Adipose-Derived Mesenchymal Stem Cells Modulate Experimental Autoimmune
      Arthritis by Modifying Early Adaptive T Cell Responses.
AB  - Mesenchymal stem cells (MSCs) are multipotent stromal cells with
      immunosuppressive properties. They have emerged as a very promising treatment for
      autoimmunity and inflammatory diseases such as rheumatoid arthritis. Recent data
      have identified that GM-CSF-expressing CD4 T cells and Th17 cells have critical
      roles in the pathogenesis of arthritis and other inflammatory diseases. Although
      many studies have demonstrated that MSCs can either prevent or suppress
      inflammation, no studies have addressed their modulation on GM-CSF-expressing CD4
      T cells and on the plasticity of Th17 cells. To address this, a single dose of
      human expanded adipose-derived mesenchymal stem cells (eASCs) was administered to
      mice with established collagen-induced arthritis. A beneficial effect was
      observed soon after the infusion of the eASCs as shown by a significant decrease
      in the severity of arthritis. This was accompanied by reduced number of
      pathogenic GM-CSF(+) CD4(+) T cells in the spleen and peripheral blood and by an
      increase in the number of different subsets of regulatory T cells like FOXP3(+)
      CD4(+) T cells and IL10(+) IL17(-) CD4(+) T cells in the draining lymph nodes
      (LNs). Interestingly, increased numbers of Th17 cells coexpressing IL10 were also
      found in draining LNs. These results demonstrate that eASCs ameliorated arthritis
      after the onset of the disease by reducing the total number of pathogenic GM
      CSF(+) CD4(+) T and by increasing the number of different subsets of regulatory T
      cells in draining LNs, including Th17 cells expressing IL10. All these cellular
      responses, ultimately, lead to the reestablishment of the regulatory/inflammatory
      balance in the draining LNs.

PMID- 26205965
TI  - Error in the Abstract in the Article by Maldini et al (Arthritis Care Res
      [Hoboken], March 2014).

PMID- 26205966
TI  - Involvement of p38 MAPK in the Anticancer Activity of Cultivated Cordyceps
      militaris.
AB  - Cordyceps militaris is a traditional Chinese medicine frequently used for tonic
      and therapeutic purposes. Reports from our laboratory and others have
      demonstrated that extracts of the cultivated fruiting bodies of C. militaris (CM)
      exhibit a potent cytotoxic effect against many cancer cell lines, especially
      human leukemia cells. Here, we further investigated the underlying mechanism
      through which CM is cytotoxic to cancer cells. The CM-mediated induction of PARP
      cleavage and its related DNA damage signal (gammaH2AX) was diminished by caspase
      inhibitor I. In contrast, a ROS scavenger failed to prevent CM-mediated leukemia
      cell death. Moreover, two signaling molecules, AKT and p38 MAPK, were activated
      during the course of apoptosis induction. Employing MTT analysis, we found that a
      p38 MAPK inhibitor but not an AKT inhibitor could rescue cells from CM-mediated
      cell death, as well as inhibit the cleavage of PARP, formation of apoptotic
      bodies and up-regulation of the gammaH2AX signal. These results suggest that CM
      mediated leukemia cell death occurs through the activation of the p38 MAPK
      pathway, indicating its potential therapeutic effects against human leukemia. 

PMID- 26205967
TI  - Orostachys japonicus Suppresses Osteoclast Differentiation by Inhibiting NFATc1
      Expression.
AB  - The herb Orostachys japonicus has been traditionally used to treat chronic
      diseases, such as hepatitis, hemorrhoids, and cancer, in Asia. In this study, we
      investigated the effect of Orostachys japonicus water extract (OJWE) on the
      receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast
      differentiation and bone loss. We found that OJWE inhibited RANKL-induced
      osteoclast differentiation in a dose-dependent manner without affecting bone
      resorption in bone marrow-derived macrophage cells. Interestingly, OJWE
      significantly reduced serum levels of C-terminal telopeptide of type 1 collagen
      and tartrate-resistant acid phosphatase (TRAP) 5b, markers of bone resorption and
      osteoclast number, respectively, in an animal model of bone loss. Furthermore,
      OJWE suppressed the RANKL-induced up-regulation of nuclear factor of activated T
      cells cytoplasmic 1 (NFATc1) expression, and activation of the p38 signaling
      pathway, but prevented the RANKL-mediated down-regulation of interferon
      regulatory factor-8 (IRF-8), which is known to be an anti-osteoclastogenic factor
      that represses NFATc1 expression. We also identified gallic acid and quercetin-3
      O-beta-D-glucoside as the OJWE components that inhibit RANKL-induced osteoclast
      differentiation. These results suggest that OJWE inhibits osteoclast
      differentiation by inhibiting RANKL-induced NFATc1 expression, which prevents
      osteoclast differentiation and bone loss. The present study elucidated a
      mechanism of action underlying the inhibitory effect of OJWE on osteoclast
      differentiation. Our findings suggest that O. japonicus has therapeutic potential
      for use in the treatment of bone diseases.

PMID- 26205968
TI  - Inhibitory Effects of Purple Sweet Potato Leaf Extract on the Proliferation and
      Lipogenesis of the 3T3-L1 Preadipocytes.
AB  - Purple sweet potato leaves (PSPLs) are healthy vegetable that is rich in anti
      oxidants. A solution of boiling water extract of PSPL (PSPLE) is believed to be
      able to prevent obesity and metabolic syndrome in the countryside of Taiwan, but
      its efficacy has not yet been verified. The purpose of this study was to
      investigate the possible anti-adipogenesis effect of PSPLE in vitro. PSPLE was
      used to treat the 3T3-L1 cells, and the effects on cell proliferation and
      adipogenesis were investigated. The results showed that PSPLE caused a dose
      dependent decrease in the cell proliferation of 3T3-L1 preadipocytes, but did not
      alter the cell viability. In addition, PSPLE induced ERK inactivation in the 3T3
      L1 preadipocytes. Furthermore, pre-treatment of confluent 3T3-L1 cells with PSPLE
      led to reduced lipid accumulation in differentiated 3T3-L1 cells. The inhibition
      of lipogenesis could result from the PSPLE-induced down-regulation of the
      expression of the C/EBPalpha and SREBP-1 transcription factors during 3T3-L1
      adipocyte differentiation. These results suggest that PSPLE not only inhibits
      cell proliferation at an early stage but also inhibits adipogenesis at a later
      stage of the differentiation program. 

PMID- 26205969
TI  - Articulating "Archiannelids": Phylogenomics and Annelid Relationships, with
      Emphasis on Meiofaunal Taxa.
AB  - Annelid disparity has resulted in morphological-based classifications that
      disagree with phylogenies based on Sanger sequencing and phylogenomic analyses.
      However, the data used for the latter studies came from various sources and
      technologies, involved poorly occupied matrices and lacked key lineages. Here, we
      generated a new Illumina-based data set to address annelid relationships from a
      fresh perspective, independent from previously generated data and with nearly
      fully occupied matrices. Our sampling reflects the span of annelid diversity,
      including two symbiotic annelid groups (Myzostomida and Spinther) and five
      meiofaunal groups once referred to as part of Archiannelida (three from
      Protodrilida, plus Dinophilus and Polygordius). As well as the placement of these
      unusual annelids, we sought to address the overall phylogeny of Annelida, and
      provide a new perspective for naming of major clades. Our results largely
      corroborate the phylogenomic results of Weigert et al. (2014; Illuminating the
      base of the annelid tree using transcriptomics. Mol Biol Evol. 31:1391-1401),
      with "Magelona + Owenia" and Chaetopteridae forming a grade with respect to all
      other annelids. Echiura and Sipuncula are supported as being annelid groups, with
      Sipuncula closest to amphinomids as sister group to Sedentaria and Errantia. We
      recovered the three Protodrilida terminals as sister clade to Phyllodocida and
      Eunicida (=clade Aciculata). We therefore place Protodrilida as part of Errantia.
      Polygordius was found to be sister group to the scaleworm terminal and the
      possibility that it is a simplified scaleworm clade, as has been shown for the
      former family Pisionidae, is discussed. Our results were equivocal with respect
      to Dinophilus, Myzostomida, and Spinther possibly owing to confounding long
      branch effects. 

PMID- 26205970
TI  - Ready, steady, go! What do histopathology trainees think they need from training
      to enable them to develop autonomy in surgical pathology reporting?
AB  - AIMS: This is a qualitative study of the perceived learning needs of trainees for
      graded responsibility in histopathological training in the UK. METHODS: A focus
      group with trainees and interviews with consultants was carried out. Participants
      were asked 'What do you perceive are the learning needs of histopathology
      trainees to develop skills for safe and confident independent reporting in
      surgical histopathology?' Data was analysed using open coding content analysis
      for items relating to training content and structure. RESULTS: Trainees and
      consultants perceived a need for a case load of around 100 specimens per week
      with a continuously variable case mix. It was thought necessary to be the
      principal presenter of cases at multidisciplinary team meetings. There was a
      perceived need for adequate amounts of supervision by consultants using double
      headed microscopes and sufficient time to develop skills in microscopic visual
      perception through detailed feature discussion, not necessarily related to
      specific diagnoses. Being able to write clear histopathology reports, developing
      the ability to recognise normal histology and to be aware of diagnostic pitfalls
      were also thought to be important. CONCLUSIONS: Our findings may inform
      efficacious implementation of graded responsibility in histopathology departments
      and be used as a sound basis for further research.

PMID- 26205971
TI  - Nuclear smears observed in H&E-stained thrombus sections are neutrophil
      extracellular traps.

PMID- 26205972
TI  - Assessment of left sided filling dynamics in diastolic dysfunction using cardiac
      computed tomography.
AB  - BACKGROUND: Left ventricular (LV) diastolic dysfunction (DD) often accompanies
      coronary artery disease but is difficult to assess since it involves a complex
      interaction between LV filling and left atrial (LA) emptying. OBJECTIVE: To
      characterize simultaneous changes in LA and LV volumes using cardiac computed
      tomography (CT) in a group of patients with various grades of DD based on
      echocardiography. METHODS: We identified 35 patients with DD by echocardiography,
      who had also undergone cardiac CT, and 35 age-matched normal controls. LV and LA
      volumes were measured every 10% of the RR interval, using semi-automatic
      software. From these, - systolic, early-diastolic and late-diastolic volume
      changes were calculated, and additional parameters of diastolic filling derived.
      Conduit volume was defined as the difference between the LV and LA early
      diastolic volume change. RESULTS: Patients with DD had significantly larger LV
      mass, and LA volumes, reduced early emptying volumes and increased conduit volume
      as percent of early LV filling (All p<0.001). LA function, manifesting as total
      emptying fraction (LATEF), decreased proportionately with worsening grades of DD
      (p<0.001). LA contractile function was maintained until advanced grade-3 DD. By
      receiver operating characteristic analysis, LATEF had an AUC of 0.88 to separate
      between normals and DD. At a threshold of <42.5%, LATEF has 97% sensitivity and
      69% specificity to detect DD. CONCLUSIONS: DD is characterized by reduced LA
      function and an alteration in the relative contributions of the atrial emptying
      and conduit volume components of early LV filling. In patients undergoing cardiac
      CT, it is possible to identify the presence and severity of DD.

PMID- 26205973
TI  - Pneumothorax size measurements on digital chest radiographs: Intra- and inter-
      rater reliability.
AB  - PURPOSE: Detailed and reliable methods may be important for discussions on the
      importance of pneumothorax size in clinical decision-making. Rhea's method is
      widely used to estimate pneumothorax size in percent based on chest X-rays (CXRs)
      from three measure points. Choi's addendum is used for anterioposterior
      projections. The aim of this study was to examine the intrarater and interrater
      reliability of the Rhea and Choi method using digital CXR in the ward based PACS
      monitors. MATERIALS AND METHODS: Three physicians examined a retrospective series
      of 80 digital CXRs showing pneumothorax, using Rhea and Choi's method, then
      repeated in a random order two weeks later. We used the analysis of variance
      technique by Eliasziw et al. to assess the intrarater and interrater reliability
      in altogether 480 estimations of pneumothorax size. RESULTS: Estimated
      pneumothorax sizes ranged between 5% and 100%. The intrarater reliability
      coefficient was 0.98 (95% one-sided lower-limit confidence interval C 0.96), and
      the interrater reliability coefficient was 0.95 (95% one-sided lower-limit
      confidence interval 0.93). CONCLUSION: This study has shown that the Rhea and
      Choi method for calculating pneumothorax size has high intrarater and interrater
      reliability. These results are valid across gender, side of pneumothorax and
      whether the patient is diagnosed with primary or secondary pneumothorax.

PMID- 26205974
TI  - Detecting dementia in patients with normal neuropsychological screening by Short
      Smell Test and Palmo-Mental Reflex Test: an observational study.
AB  - BACKGROUND: General practitioners (GPs) are in best position to suspect dementia.
      Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT) are widely
      used. Additional neurological tests may increase the accuracy of diagnosis. We
      aimed to evaluate diagnostic ability to detect dementia with a Short Smell Test
      (SST) and Palmo-Mental Reflex (PMR) in patients whose MMSE and CDT are normal,
      but who show signs of cognitive dysfunction. METHODS: This was a 3.5-year cross
      sectional observational study in the Memory Clinic of the University Department
      of Geriatrics in Bern, Switzerland. Participating patients with normal MMSE (>26
      points) and CDT (>5 points) were referred by GPs because they suspected dementia.
      All were examined according to a standardized protocol. Diagnosis of dementia was
      based on DSM-IV TR criteria. We used SST and PMR to determine if they accurately
      detected dementia. RESULTS: In our cohort, 154 patients suspected of dementia had
      normal MMSE and CDT test results. Of these, 17 (11%) were demented. If SST or PMR
      were abnormal, sensitivity was 71% (95% CI 44-90%), and specificity 64% (95% CI
      55-72%) for detecting dementia. If both tests were abnormal, sensitivity was 24%
      (95% CI 7-50%), but specificity increased to 93% (95% CI 88-97%). CONCLUSION:
      Patients suspected of dementia, but with normal MMSE and CDT results, may benefit
      if SST and PMR are added as diagnostic tools. If both SST and PMR are abnormal,
      this is a red flag to investigate these patients further, even though their
      negative neuropsychological screening results.

PMID- 26205975
TI  - Thoracic ultrasound for the diagnosis of pneumonia in adults: a meta-analysis.

PMID- 26205976
TI  - The conserved carboxyl domain of MorC, an inner membrane protein of
      Aggregatibacter actinomycetemcomitans, is essential for membrane function.
AB  - Morphogenesis protein C (MorC) of Aggregatibacter actinomycetemcomitans is
      important for maintaining the membrane morphology and integrity of the cell
      envelope of this oral pathogen. The MorC sequence and operon organization were
      found to be conserved in Gammaproteobacteria, based on a bioinformatic analysis
      of 435 sequences from representative organisms. Functional conservation of MorC
      was investigated using an A. actinomycetemcomitans morC mutant as a model system
      to express MorC homologs from four phylogenetically diverse representatives of
      the Gammaproteobacteria: Haemophilus influenzae, Escherichia coli, Pseudomonas
      aeruginosa, and Moraxella catarrhalis. The A. actinomycetemcomitans strains
      expressing the homologous proteins were assessed for sensitivity to bile salts,
      leukotoxin secretion, autoaggregation and membrane morphology. MorC from the most
      closely related organism (H. influenzae) was functionally identical to MorC from
      A. actinomycetemcomitans. However, the genes from more distantly related
      organisms restored some but not all A. actinomycetemcomitans mutant phenotypes.
      In addition, deletion mutagenesis indicated that the most conserved portion of
      the protein, the C-terminus DUF490 domain, was necessary to maintain the
      integrity of the membrane. Deletion of the last 10 amino acids of this domain of
      the A. actinomycetemcomitans MorC protein was sufficient to disrupt membrane
      stability and leukotoxin secretion. The data suggest that the MorC sequence is
      functionally conserved across Gammaproteobacteria and the C-terminus of the
      protein is essential for maintaining membrane physiology.

PMID- 26205977
TI  - Highly condensed chromatins are formed adjacent to subtelomeric and decondensed
      silent chromatin in fission yeast.
AB  - It is generally believed that silent chromatin is condensed and transcriptionally
      active chromatin is decondensed. However, little is known about the relationship
      between the condensation levels and gene expression. Here we report the
      condensation levels of interphase chromatin in the fission yeast
      Schizosaccharomyces pombe examined by super-resolution fluorescence microscopy.
      Unexpectedly, silent chromatin is less condensed than the euchromatin.
      Furthermore, the telomeric silent regions are flanked by highly condensed
      chromatin bodies, or 'knobs'. Knob regions span ~50 kb of sequence devoid of
      methylated histones. Knob condensation is independent of HP1 homologue Swi6 and
      other gene silencing factors. Disruption of methylation at lysine 36 of histone
      H3 (H3K36) eliminates knob formation and gene repression at the subtelomeric and
      adjacent knob regions. Thus, epigenetic marks at H3K36 play crucial roles in the
      formation of a unique chromatin structure and in gene regulation at those regions
      in S. pombe. 

PMID- 26205978
TI  - Diverse coordination modes in tin analogues of a cyclopentadienyl anion depending
      on the substituents on the tin atom.
AB  - Reactions of an anionic heavy ruthenocene with CCl4, MeI, EtBr and Me3SiCl
      afforded the first stannole monoanion complexes. Surprisingly, coordination modes
      of the stannole rings are highly dependent on the substituents on the tin atom.
      The chloro derivative exhibits a eta(4)-fashion-like coordination mode with a
      bent stannole ring, whereas the trimethylsilyl derivative adopts the conventional
      eta(5)-coordination mode. Coordination modes of the alkyl derivatives are in
      between the two types. Cyclic voltammograms for these complexes reveal that the
      electron-donating character of the stannole ligand becomes stronger as the
      stannole ring becomes planar. Theoretical calculations elucidate that the
      different coordination modes originate from both electronegativity of an adjacent
      atom to the tin atom and bulkiness of a substituent on the tin atom. 

PMID- 26205979
TI  - Cancer Patients' Informational Needs: Qualitative Content Analysis.
AB  - Understanding the informational needs of cancer patients is a requirement to plan
      any educative care program for them. The aim of this study was to identify
      Iranian cancer patients' perceptions of informational needs. The study took a
      qualitative approach. Semi-structured interviews were held with 25 cancer
      patients in two teaching hospitals in Iran. Transcripts of the interviews
      underwent conventional content analysis, and categories were extracted. The
      results came under two main categories: disease-related informational needs and
      information needs related to daily life. Disease-related informational needs had
      two subcategories: obtaining information about the nature of disease and
      obtaining information about disease prognosis. Information needs related to daily
      life also had two subcategories: obtaining information about healthy lifestyle
      and obtaining information about regular activities of daily life. The findings
      provide deep understanding of cancer patients' informational needs in Iran.

PMID- 26205980
TI  - The burden of cervical pre-cancer and cancer in HIV positive women in Zambia: a
      modeling study.
AB  - BACKGROUND: HIV infection is associated with a higher incidence of precancerous
      cervical lesions and their progression to invasive cervical cancer (ICC). Zambia
      is a global epicenter of HIV and ICC, yet the overall burden of cervical pre
      cancer [cervical intraepithelial neoplasia 3 (CIN3)] and ICC among its HIV
      positive adult female population is unknown. The objective of this study was to
      determine the burden of cervical disease among HIV positive women in Zambia by
      estimating the number with CIN3 and ICC. METHODS: We conducted a cross-sectional
      study among 309 HIV positive women attending screening in Lusaka (Zambia's most
      populated province) to measure the cervical disease burden by visual inspection
      with acetic acid enhanced by digital cervicography (DC), cytology, and histology.
      We then used estimates of the prevalence of CIN3 and ICC from the cross-sectional
      study and Spectrum model-based estimates for HIV infection among Zambian women to
      estimate the burden of CIN3 and ICC among HIV positive women nationally. RESULTS:
      Over half (52 %) of the study participants screened positive by DC, while 45 %
      had cytologic evidence of high grade squamous intraepithelial lesions (SIL) or
      worse. Histopathologic evaluation revealed that 20 % of women had evidence of
      CIN2 or worse, 11 % had CIN3 or worse, and 2 % had ICC. Using the Spectrum model,
      we therefore estimate that 34,051 HIV positive women in Zambia have CIN3 and
      7,297 have ICC. CONCLUSIONS: The DC, cytology, and histology results revealed a
      large cervical disease burden in this previously unscreened HIV positive
      population. This very large burden indicates that continued scale-up of cervical
      cancer screening and treatment is urgently needed.

PMID- 26205981
TI  - Effects of breathing frequency on the heart rate deceleration capacity and heart
      rate acceleration capacity.
AB  - PURPOSE: The deceleration capacity (DC) and acceleration capacity (AC) of heart
      rate as well as the respiratory rate predict outcome after acute myocardial
      infarction. We evaluated the relation between breathing frequency and both DC and
      AC, as well as the difference between them. METHODS: We studied fourteen healthy
      young adults who breathed spontaneously and controlled their breathing to rates
      of 0.1, 0.2, 0.3, and 0.4 Hz in a supine position. A 5-min R-R interval time
      series without movement artifacts or ectopic beats was obtained from each studied
      period and scanned to identify the anchor points that were characterized by a
      value longer or shorter than the preceding value. Averaged changes of R-R
      intervals surrounding the deceleration and acceleration anchors were calculated
      as DC and AC, respectively. RESULTS: The magnitudes of DC and AC increased
      progressively as breathing frequency decreased (Both p < 0.001 by one-way
      repeated-measures analysis of variance). The magnitude of DC was larger than the
      magnitude of AC during 0.1-Hz breathing (95 % confidence interval of their
      difference: 1.7-9.7 ms), while the difference between them reduced to near zero
      at higher frequencies. CONCLUSIONS: Slow breathing enhances the magnitudes of DC
      and AC simultaneously under the conditions used in this study. The increase in
      the magnitude of DC is significantly greater than that of AC.

PMID- 26205982
TI  - Obesity-related differences in neuromuscular fatigue in adolescent girls.
AB  - PURPOSE: The aim of this study was to investigate the effect of obesity on
      neuromuscular fatigue in adolescent girls. METHODS: Twelve lean (13.6 +/- 0.8
      years) and 12 obese (13.9 +/- 0.9 years) girls repeated 5-s maximal voluntary
      contractions (MVC) of the knee extensors until the generated torque reached 55 %
      of its initial value. Magnetic stimulations were delivered to the femoral nerve
      every five MVCs to follow the course of voluntary activation (VA) and potentiated
      twitch torque (Qtwpot). RESULTS: Torque reached 55 % of its initial value after
      52.6 +/- 20.4 and 74.9 +/- 22.8 repetitions in obese and lean girls, respectively
      (p < 0.01). Furthermore, the decline of VA was smaller in obese girls (p <
      0.001). In contrast, Qtwpot decreased to a greater extent in obese girls (p <
      0.05). CONCLUSIONS: Obese girls fatigue faster than their lean counterparts. The
      peripheral factors mainly account for fatigue in obese girls, whereas central
      factors are mainly involved in lean girls.

PMID- 26205983
TI  - One mutation, two phenotypes: a single nonsense mutation of the CTSC gene causes
      two clinically distinct phenotypes.
AB  - BACKGROUND: Papillon-Lefevre syndrome (PLS; OMIM 245000) and Haim-Munk syndromes
      (HMS; OMIM 245010) are phenotypic variants of the same rare disease caused by
      mutations of the cathepsin C (CTSC) gene, and they exhibit autosomal recessive
      inheritance. AIMS: To identify diseases caused by mutations of the CTSC gene in
      two Hungarian patients and to perform haplotype analysis to elucidate any
      familial relationship between them. METHODS: Mutation screening and polymorphism
      analysis were performed by direct sequencing of the CTSC gene. RESULTS: Mutation
      screening of the CTSC gene from the two patients revealed the presence of the
      same homozygous nonsense mutation (c.748C/T; p.Arg250X). However, one patient
      exhibited the PLS phenotype and the other the HMS phenotype. Although these
      patients were not aware that they were related, haplotype analysis, especially
      the genotypes of the rs217116 and the rs217115 polymorphisms, clearly indicated
      that the patients carry the same haplotype, whereas the unrelated healthy
      controls carried several different haplotypes. CONCLUSIONS: Our results
      demonstrate that PLS and HMS are phenotypic variants of the same disease and,
      additionally, exclude the presence of a putative genetic modifier factor within
      the CTSC gene that is responsible for the development of the two phenotypes. We
      suggest that this putative genetic modifier factor is located outside the CTSC
      gene, or alternatively, that the development of the different phenotypes is the
      consequence of different environmental or lifestyle factors.

PMID- 26205984
TI  - [CAMIC Recommendations for Surgical Laparoscopy in Non-Obstetric Indications
      during Pregnancy].
AB  - In the operative surgical primary care, the laparoscopic surgical technique has
      firmly established itself in recent years. Meanwhile, in the normal population
      over 90 % of all cholecystectomies and over 80 % of all appendectomies are
      performed in a minimally invasive manner. The proven benefits of the laparoscopic
      surgical technique, compared with conventional open surgery, are a comparatively
      rapid early postoperative recovery with early resumption of the general physical
      and occupational activity. As these benefits are equally applicable for necessary
      interventions during pregnancy, in recent years laparoscopy has become the
      preferred treatment for non-obstetric indications in the gravid patient. Overall,
      it can be assumed that such interventions have to be performed in approximately 2
      % of all pregnant patients. Numerous studies have proven here that the use of
      laparoscopic techniques, in particular for the expectant mother, is safe and not
      associated with an increased risk. On the other hand, the current pregnancy makes
      necessary an adapted approach to the solution of surgical problems to ensure the
      protection of the unborn child. On the basis of currently available data
      situation, recommendations are formulated which can be used as a decision-making
      support for a variety of clinical situations.

PMID- 26205985
TI  - [Chances and Potential of a Modern Surgical Skills Lab as Substantial Practical
      Part of the Study of Human Medicine - "The Magdeburg Model"].
AB  - Introduction: Surgical education of medical students within "skills labs" have
      not been standardised throughout Germany as yet; there is a substantial impact of
      available aspects such as personal and space at the various medical schools. Aim:
      The aim of this contribution is to illustrate the concept of a surgical skills
      lab in detail, including curricular teaching and integrated facultative courses
      at the Medical School, University of Magdeburg ("The Magdeburg Model") in the
      context of a new and reconstructed area for the skills lab at the Magdeburg's
      apprenticeship center for medical basic abilities (MAMBA). Method: We present an
      overview on the spectrum of curricular and facultative teaching activities within
      the surgical part of the skills lab. Student evaluation of this teaching concept
      is implemented using the programme "EvaSys" and evaluation forms adapted to the
      single courses. Results: By establishing MAMBA, the options for a practice
      related surgical education have been substantially improved. Student evaluations
      of former courses presented within the skills lab and the chance of moving the
      skills lab into a more generous and reconstructed area led to a reorganisation of
      seminars and courses. New additional facultative courses held by student tutors
      have been introduced and have shown to be of great effect, in particular, because
      of their interdisciplinary character. Conclusion: Practice-related surgical
      education within a skills lab may have the potential to effectively prepare
      medical students for their professional life. In addition, it allows one to
      present and teach the most important basic skills in surgery, which need to be
      pursued by every student. An enthusiastic engagement of the Office for Student
      Affairs can be considered the crucial and indispensable link between clinical
      work and curricular as well as facultative teaching with regard to organisation
      and student evaluation. The practice-related teaching parts and contents at the
      surgical section of a skills lab should be integrated into the National
      Competence-based Catalogue of Teaching Aims in Medicine ("NKLM").

PMID- 26205986
TI  - Hydrodynamic Microgap Voltammetry under Couette Flow Conditions: Electrochemistry
      at a Rotating Drum in Viscous Poly(ethylene glycol).
AB  - Electrochemical processes in highly viscous media such as poly(ethylene glycol)
      (herein PEG200) are interesting for energy-conversion applications, but
      problematic due to slow diffusion causing low current densities. Here, a
      hydrodynamic microgap experiment based on Couette flow is introduced for an
      inlaid disc electrode approaching a rotating drum. Steady-state voltammetric
      currents are independent of viscosity and readily increased by two orders of
      magnitude with further potential to go to higher rotation rates and nanogaps. A
      quantitative theory is derived for the prediction of currents under high-shear
      Couette flow conditions and generalised for different electrode shapes. The 1,1'
      ferrocene dimethanol redox probe in PEG200 (D=1.4*10-11 m2  s-1 ) is employed and
      data are compared with 1) a Levich-type equation expressing the diffusion
      convection-limited current and 2) a COMSOL simulation model providing a potential
      dependent current trace.

PMID- 26205987
TI  - Income adequacy and education associated with the prevalence of obesity in rural
      Saskatchewan, Canada.
AB  - BACKGROUND: Obesity is prevalent in rural communities in Canada, however little
      is known about the social determinants of health and obesity in rural
      populations. Socioeconomic status has been found to be inversely associated with
      the risk of obesity in developed countries. This study investigated the
      relationship between income adequacy, education and obesity in a rural setting.
      METHODS: The study used data from 5391 adults aged 18-69 who participated in the
      Saskatchewan Rural Health Study in 2010. Participants completed a survey that
      included questions about location of residence, body weight, height, and socio
      demographic and behavioral factors. Obesity was defined as body mass index being
      >= 30 kg/m(2). Logistic regression using generalized estimating equation was
      conducted to assess the associations of income adequacy and education level with
      the prevalence of obesity taking covariates into consideration. RESULTS:
      Approximately a third of the participants were obese and the prevalence of
      obesity was similar for men and women. The prevalence of obesity was
      significantly higher for rural residents not living on farm compared with those
      living on farm (p < 0.05). After adjustment for potential confounders, the risk
      of obesity was increased for those with <= 12 years of education compared with
      those with > 12 years of education (aOR: 1.18; 95% CI: 1.05-1.34). Low income
      adequacy was significantly associated with an increased risk of obesity but only
      among those not living on farm (aOR: 1.80; 95% CI: 1.16-2.79). CONCLUSIONS: Home
      location was associated with obesity prevalence in rural Saskatchewan and
      modified the influence of income adequacy, but not the influence of education, on
      obesity. Adults not living on farm had an increased risk of obesity and showed a
      significant impact of income adequacy on obesity.

PMID- 26205988
TI  - The Spatial Mixing of Genomes in Secondary Contact Zones.
AB  - Recent genomic studies have highlighted the important role of admixture in
      shaping genome-wide patterns of diversity. Past admixture leaves a population
      genomic signature of linkage disequilibrium (LD), reflecting the mixing of
      parental chromosomes by segregation and recombination. These patterns of LD can
      be used to infer the timing of admixture, but the results of inference can depend
      strongly on the assumed demographic model. Here, we introduce a theoretical
      framework for modeling patterns of LD in a geographic contact zone where two
      differentiated populations have come into contact and are mixing by diffusive
      local migration. Assuming that this secondary contact is recent enough that
      genetic drift can be ignored, we derive expressions for the expected LD and
      admixture tract lengths across geographic space as a function of the age of the
      contact zone and the dispersal distance of individuals. We develop an approach to
      infer age of contact zones, using population genomic data from multiple spatially
      sampled populations by fitting our model to the decay of LD with recombination
      distance. To demonstrate an application of our model, we use our approach to
      explore the fit of a geographic contact zone model to three human genomic data
      sets from populations in Indonesia, Central Asia, and India and compare our
      results to inference under different demographic models. We obtain substantially
      different results from those of the commonly used model of panmictic admixture,
      highlighting the sensitivity of admixture timing results to the choice of
      demographic model. 

PMID- 26205989
TI  - Do Molecular Markers Inform About Pleiotropy?
AB  - The availability of dense panels of common single-nucleotide polymorphisms and
      sequence variants has facilitated the study of statistical features of the
      genetic architecture of complex traits and diseases via whole-genome regressions
      (WGRs). At the onset, traits were analyzed trait by trait, but recently, WGRs
      have been extended for analysis of several traits jointly. The expectation is
      that such an approach would offer insight into mechanisms that cause trait
      associations, such as pleiotropy. We demonstrate that correlation parameters
      inferred using markers can give a distorted picture of the genetic correlation
      between traits. In the absence of knowledge of linkage disequilibrium
      relationships between quantitative or disease trait loci and markers, speculating
      about genetic correlation and its causes (e.g., pleiotropy) using genomic data is
      conjectural. 

PMID- 26205990
TI  - Targeted Gene Disruption by Ectopic Induction of DNA Elimination in Tetrahymena.
AB  - Tetrahymena is a useful eukaryotic model for biochemistry and molecular cell
      biology studies. We previously demonstrated that targeted ectopic DNA
      elimination, also called co-Deletion (coDel), can be induced by the introduction
      of an internal eliminated sequence (IES)-target DNA chimeric construct. In this
      study, we demonstrate that coDel occurs at most of the loci tested and can be
      used for the production of somatic gene KO strains. We also showed that coDel at
      two loci can be simultaneously induced by a single transformation; thus, coDel
      can be used to disrupt multiple gene loci in a single cell. Therefore, coDel is a
      useful tool for functional genetics in Tetrahymena and further extends the
      usefulness of this model organism. 

PMID- 26205991
TI  - A New Guideline on Treatment of Hypertension in Those with Coronary Artery
      Disease: Scientific Statement From the American Heart Association, American
      College of Cardiology, and American Society of Hypertension About Treatment of
      Hypertension in Patients with Coronary Artery Disease.
AB  - Hypertension is a major risk factor for coronary artery disease (CAD) and the two
      frequently coexist. The peak cardiology and hypertension societies of the United
      States recently published new guidelines on the treatment of hypertension in
      people with CAD. The guidelines update those previously issued eight years
      previously in the light of new trial data. However, for the most part they will
      validate what cardiologists are already doing in these patients. The major change
      is resetting of the blood pressure general treatment target for most people with
      hypertension and CAD from 130/80mm Hg to 140/90mm Hg. It is arguable that the
      evidence supporting the new target is any stronger than that supporting the old.
      While this will remain controversial in the absence of good data on the relative
      benefits of different treatment targets in hypertension it is in line with trends
      from a number of other general hypertension guidelines. 

PMID- 26205993
TI  - Can a T2 hyperintense rim sign differentiate uterine leiomyomas from other solid
      adnexal masses?
AB  - PURPOSE: To investigate the incidence of high T2 signal rims surrounding
      leiomyomas, evaluate if a particular T2-weighted sequence is more effective in
      depicting this rim, and determine if this sign is useful in differentiating
      pedunculated leiomyomas from other solid adnexal masses. MATERIALS AND METHODS:
      In this retrospective study, two radiologists evaluated 233 T2 dark pelvic masses
      (223 uterine leiomyomas and 10 ovarian fibromas) in 60 women (mean age 47) on
      Magnetic resonance imaging for the presence of a high signal rim. Three different
      T2-weighted sequences were reviewed independently for uterine leiomyomas: half
      Fourier acquisition single-shot turbo spin echo (HASTE), SPACE, and T2 with fat
      saturation (T2 FS). Only T2 FS images were available for 10 fibromas. A consensus
      review was conducted for discrepant cases. Statistical analyses were performed
      using Fisher's exact test, kappa test, and ANOVA RESULTS: For 223 uterine
      leiomyomas, 23% (95% CI 17.8-28.9%) demonstrated a high T2 signal rim sign on T2
      FS compared with 4.9% (95% CI 2.6-8.9%) for HASTE and 6.7% (95% CI 3.9-11.1%) for
      SPACE. The difference between the number of positive rims on T2 FS relative-HASTE
      and SPACE was statistically significant (p < 0.001). For ovarian fibromas, 40%
      (95% CI 16.9-68.8%) were classified positive for a rim sign. CONCLUSION: A high
      T2 signal rim sign was present for up to 23% of uterine leiomyomas and the T2 FS
      sequence detected this rim sign most frequently. Up to 40% of ovarian fibromas
      can also have a T2 rim sign and, therefore, a solid adnexal mass with a T2 rim
      sign cannot be assumed to represent a pedunculated leiomyoma.

PMID- 26205994
TI  - CCL2 and CCR2 are Essential for the Formation of Osteoclasts and Foreign Body
      Giant Cells.
AB  - Osteoclasts are multinucleated cells responsible for bone resorption. They are
      derived from the fusion of cells in the monocyte/macrophage lineage. Monocytes
      and macrophages can also fuse to form foreign body giant cells (FBGC). Foreign
      body giant cells are observed at the interface between a host and a foreign body
      such as implants during a foreign body reaction. Macrophages are attracted to the
      site of bone resorption and foreign body reactions by different cytokines.
      Chemokine (C-C) ligand-2 (CCL2) is an important chemotactic factor and binds to a
      receptor CCR2. In this study we investigated the importance of CCL2 and the
      receptor CCR2 in the formation of osteoclasts and FBGC. CCL2 mRNA was more highly
      expressed in giant cell culture than macrophages, being 9-fold and 16-fold more
      abundant in osteoclasts and FBGC respectively. Significantly fewer osteoclasts
      and FBGC were cultured from the bone marrow of CCL2 and CCR2 knockout mice, when
      compared to wild type. Not only were the number of giant cells reduced but there
      was a significant reduction in the number of nuclei and the size of these cells
      in the cultures of CCL2 and CCR2 knockout mice. Formation of osteoclasts and FBGC
      were recovered in cultures by addition of exogenous CCL2 to the media containing
      marrow cells from CCL2-/- mice. We conclude that CCL2 and its receptor CCR2 are
      important for the formation of osteoclasts and FBGC and absence of these genes
      causes inhibition of osteoclast and FBGC formation.

PMID- 26205992
TI  - Feasibility of and agreement between MR imaging and spectroscopic estimation of
      hepatic proton density fat fraction in children with known or suspected
      nonalcoholic fatty liver disease.
AB  - PURPOSE: To assess feasibility of and agreement between magnetic resonance
      imaging (MRI) and magnetic resonance spectroscopy (MRS) for estimating hepatic
      proton density fat fraction (PDFF) in children with known or suspected
      nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Children were
      included in this study from two previous research studies in each of which three
      MRI and three MRS acquisitions were obtained. Sequence acceptability, and MRI-
      and MRS-estimated PDFF were evaluated. Agreement of MRI- with MRS-estimated
      hepatic PDFF was assessed by linear regression and Bland-Altman analysis. Age,
      sex, BMI-Z score, acquisition time, and artifact score effects on MRI- and MRS
      estimated PDFF agreement were assessed by multiple linear regression. RESULTS:
      Eighty-six children (61 boys and 25 girls) were included in this study. Slope and
      intercept from regressing MRS-PDFF on MRI-PDFF were 0.969 and 1.591%,
      respectively, and the Bland-Altman bias and 95% limits of agreement were 1.17% +/
      2.61%. MRI motion artifact score was higher in boys than girls (by 0.21, p =
      0.021). Higher BMI-Z score was associated with lower agreement between MRS and
      MRI (p = 0.045). CONCLUSION: Hepatic PDFF estimation by both MRI and MRS is
      feasible, and MRI- and MRS-estimated PDFF agree closely in children with known or
      suspected NAFLD.

PMID- 26205995
TI  - A newly identified mouse hypothalamic area having bidirectional neural
      connections with the lateral septum: the perifornical area of the anterior
      hypothalamus rich in chondroitin sulfate proteoglycans.
AB  - While previous studies and brain atlases divide the hypothalamus into many nuclei
      and areas, uncharacterised regions remain. Here, we report a new region in the
      mouse anterior hypothalamus (AH), a triangular-shaped perifornical area of the
      anterior hypothalamus (PeFAH) between the paraventricular hypothalamic nucleus
      and fornix, that abundantly expresses chondroitin sulfate proteoglycans (CSPGs).
      The PeFAH strongly stained with markers for chondroitin sulfate/CSPGs such as
      Wisteria floribunda agglutinin and antibodies against aggrecan and chondroitin 6
      sulfate. Nissl-stained sections of the PeFAH clearly distinguished it as a region
      of comparatively low density compared to neighboring regions, the paraventricular
      nucleus and central division of the anterior hypothalamic area.
      Immunohistochemical and DNA microarray analyses suggested that PeFAH contains
      sparsely distributed calretinin-positive neurons and a compact cluster of
      enkephalinergic neurons. Neuronal tract tracing revealed that both enkephalin-
      and calretinin-positive neurons project to the lateral septum (LS), while the
      PeFAH receives input from calbindin-positive LS neurons. These results suggest
      bidirectional connections between the PeFAH and LS. Considering neuronal subtype
      and projection, part of PeFAH that includes a cluster of enkephalinergic neurons
      is similar to the rat perifornical nucleus and guinea pig magnocellular dorsal
      nucleus. Finally, we examined c-Fos expression after several types of stimuli and
      found that PeFAH neuronal activity was increased by psychological but not
      homeostatic stressors. These findings suggest that the PeFAH is a source of
      enkephalin peptides in the LS and indicate that bidirectional neural connections
      between these regions may participate in controlling responses to psychological
      stressors.

PMID- 26205996
TI  - The anterior talofibular ligament: A detailed morphological study.
AB  - The anterior talofibular ligament (ATFL) is commonly injured and may result in
      ankle instability. Good results from ATFL reconstruction have been reported;
      however complications and movement restrictions have also been observed. ATFL
      differences have been reported; however details of its precise bony attachment
      are lacking. This study provides a detailed morphology of the ATFL with respect
      to surgical and clinical applications. ATFL morphology, number of bands and the
      exact insertion points were studied in 50 formaldehyde embalmed feet. ATFL length
      was measured in different joint positions to assess its functional role: ATFL
      length varied from 18.81 mm in dorsiflexion to 21.06 mm in plantarflexion: mid
      length width and thickness were 4.97 mm and 1.01 mm respectively. The bony
      attachment lengths were also measured: mean proximal and distal bony attachment
      lengths were 4.68 mm and 3.1mm respectively, while 13.04 mm had no bony
      attachment. One (22.9%), two (56.3%) and three (20.8%) band morphologies were
      observed originating 10.37 mm anterosuperior to the lateral malleolar tip and
      inserting 3.92 mm anterior to the anterior lateral malleolar line (ALML).
      Detailed morphology of the ATFL may help in restoring injured ATFL function by
      appropriate ligament reconstruction, as well as aid the understanding of the
      mechanism of ligament injury.

PMID- 26205997
TI  - Tibialis anterior tendon rupture as a complication of first tarsometatarsal joint
      steroid injection: A case report and review of literature.
AB  - First tarsometatarsal joint steroid injection is a commonly performed procedure
      in foot and ankle practice. The joint is in close proximity to tibialis anterior
      tendon insertion. We describe a rare complication of the procedure which had to
      be treated surgically. We have also listed available treatment options based on
      literature review. 

PMID- 26205998
TI  - Effects of the site and extent of plantar cutaneous stimulation on dynamic
      balance and muscle activity while walking.
AB  - BACKGROUND: Previous studies have demonstrated that stimulating the cutaneous
      plantar sensory receptors of the foot through textured insoles improves human
      balance and walking. This study investigated the effect of medial and lateral
      zoned textured insoles using tibialis anterior/peroneus longus surface
      electromyographic activity and Centre-of-Pressure as indicators of postural
      stability while walking. METHODS: 15 asymptomatic subjects were tested using a
      within-subject randomised repeated measures design. The effect of lateral and
      medial zoned insoles of varying heights (control, 2, 4 and 6mm) on stability
      while walking under normal and impaired visual conditions was assessed. RESULTS:
      Impaired vision resulted in an increase in foot CoP variability while walking
      (p<0.05). The laterally zoned insole was associated with a significant (repeated
      measures ANOVA p<0.05) increase in the rate of medial-lateral CoP change.
      CONCLUSION: These findings suggest that the site of stimulation of the plantar
      foot cutaneous receptors may increase postural instability during walking. This
      should be considered in the design of insoles that aim to improve balance and
      reduce falls risk. The importance of vision in balance control has been
      highlighted and using impaired vision may serve as a way of trialling clinical
      products in the healthy population.

PMID- 26205999
TI  - Reconstruction of healed elongated anterior tibial and extensor hallucis longus
      tendons in a young active farmer.
AB  - A case of open traumatic lacerations of the anterior tibial tendon (ATT) and
      extensor hallucis longus (EHL) tendon that both healed in continuity but
      significantly elongated position following primary repair, resulting in foot drop
      and sagging of the great toe affecting gait and function, is presented. An
      adequate immobilization and protection in the early post-operative period is very
      important and a secure technique for reconstructing a healed elongated anterior
      tibial tendon is described. 

PMID- 26206000
TI  - Alzheimer's disease and modern lifestyle: what is the role of stress?
AB  - This Editorial highlights a study by Baglietto-Vargas et al. 2015 published in
      this issue of J. Neurochem. Stress is one of the environmental factors that can
      contribute to Alzheimer's disease pathogenesis. However, the role of modern-life
      stress has not been investigated yet. The authors reveal that modern-life stress
      reduces the number of dendritic spines in the hippocampus of Alzheimer's disease
      transgenic mice. The mechanism underlying such effect involves an increase in
      corticotropin-releasing hormone (CRH) release that stimulates the amyloid
      precursor protein (APP) processing and fosters the generation of Amyloid-beta,
      which negatively affects dendritic spines.

PMID- 26206001
TI  - [Much muscle, little brain].

PMID- 26206003
TI  - [Vascular nodules on the face bleed on contact].

PMID- 26206004
TI  - ["This fracture will heal poorly"].

PMID- 26206005
TI  - [Spouses eat more deliberately - and gain weight considerably].

PMID- 26206006
TI  - [Savior of the moribund rural practice].

PMID- 26206008
TI  - [House call to a murderer].

PMID- 26206009
TI  - [A new basal insulin].

PMID- 26206010
TI  - [The experiences are uniformly very good].

PMID- 26206011
TI  - [Sustained reduction of fracture risk in high compliance].

PMID- 26206012
TI  - [The first oral budesonide: effective in an acute episode].

PMID- 26206013
TI  - [Can I provide medical care for students after accidents?].

PMID- 26206015
TI  - [Emergency care needs the same game plan for all].

PMID- 26206016
TI  - [Clear field for the fifth round].

PMID- 26206017
TI  - [From fecalith to ileus - what the ultrasound reveals].

PMID- 26206018
TI  - [Is it an abdominal infarct?].

PMID- 26206019
TI  - [Integrating dying into life].

PMID- 26206021
TI  - [High time for an HIV test!].

PMID- 26206022
TI  - [Is general pneumococcal vaccination of value?].

PMID- 26206023
TI  - [Physical fitness prevents atrial fibrillation episodes].

PMID- 26206024
TI  - [Permanent overweight increases asthma risk in school age children].

PMID- 26206025
TI  - [No special rules for diabetics with acute urinary tract infections].

PMID- 26206026
TI  - [Shingles symptoms are gone but not the pain].

PMID- 26206028
TI  - [Do obese patients need different antihypertensive drugs?].

PMID- 26206029
TI  - [Also Z drugs are abused].

PMID- 26206030
TI  - [Gallbladder going astray].

PMID- 26206031
TI  - [New approaches in LDL cholesterol reduction].

PMID- 26206032
TI  - [Reducing blood glucose values saves diabetic patients' eyes].

PMID- 26206033
TI  - [An image of nutcracker esophagus].

PMID- 26206034
TI  - [Preventing fractures with strontium ranelate].

PMID- 26206035
TI  - [Hot spot abdomen].

PMID- 26206036
TI  - [Therapy of helicobacter pylori infection].

PMID- 26206037
TI  - [Differentiated therapy of irritable bowel syndrome in adults].

PMID- 26206038
TI  - [Limitations of the use of phytotherapy in daily practice].

PMID- 26206039
TI  - [Emergency checklist: Distal biceps tendon rupture].

PMID- 26206040
TI  - [Electrolyte disorders].

PMID- 26206041
TI  - [A specific characteristic of the diabetic foot - the diabetic-neuropathic
      osteoarthropathy].

PMID- 26206042
TI  - [Renal diagnostics in arterial hypertension].

PMID- 26206043
TI  - [Spontaneously resolving appendicitis as a religious turning point of the
      stigmatized Therese Neumann (1898-1962) of Konnersreuth].

PMID- 26206044
TI  - [Good bronchodilatation is more important than inhibiting inflammation].

PMID- 26206046
TI  - [Causal treatment of nerve damage].

PMID- 26206047
TI  - [New oral therapy option].

PMID- 26206048
TI  - [ACOS - a new fad concept or real diagnosis?].

PMID- 26206049
TI  - [Overload: preventing burnout].

PMID- 26206050
TI  - [Intestine selective therapy].

PMID- 26206051
TI  - [Combination with additive effectiveness].

PMID- 26206052
TI  - [Quality of life improves].

PMID- 26206053
TI  - [Duchenne muscular dystrophy].

PMID- 26206054
TI  - [Booster free integrase inhibition].

PMID- 26206055
TI  - [High chance for cure].

PMID- 26206056
TI  - [Long-acting basal insulin].

PMID- 26206057
TI  - [Histamine liberation is stopped].

PMID- 26206058
TI  - [Positive experience with SGLT-2 inhibitor in general practice].

PMID- 26206059
TI  - [Focus on physical training and healthy nutrition].

PMID- 26206060
TI  - [Effective prevention of coronary heart disease by early diabetes therapy].

PMID- 26206061
TI  - [Rhodiola rosea special extract: Arctic forces against stress].

PMID- 26206062
TI  - [Physician-patient relationship via internet].

PMID- 26206063
TI  - Graphenes as Efficient Metal-Free Fenton Catalysts.
AB  - Reduced graphene oxide exhibits high activity as Fenton catalyst with HO(.)
      radical generation efficiency over 82 % and turnover numbers of 4540 and 15023
      for phenol degradation and H2 O2 consumption, respectively. These values compare
      favorably with those achieved with transition metals, showing the potential of
      carbocatalysts for the Fenton reaction.

PMID- 26206064
TI  - NHS needs transformation fund to develop new models of care, say Health
      Foundation and King's Fund.

PMID- 26206065
TI  - Ultrasound combined with electrodiagnosis improves lesion localization and
      outcome in posterior interosseous neuropathy.
AB  - INTRODUCTION: Posterior interosseous nerve (PIN) syndrome is a rare compression
      neuropathy. Electrodiagnostic studies (EDx) combined with neuromuscular
      ultrasound (US) enable precise lesion localization and may improve patient
      outcome. METHODS: In 4 patients with finger extension weakness, US was used to
      accurately localize concentric electromyographic (EMG) needle placement in PIN
      muscles and to visualize the lesion site. RESULTS: EMG with US guidance showed
      decreased recruitment with abnormal configuration in PIN muscles. Active
      denervation was not always observed. US scanning demonstrated larger PIN diameter
      in the affected arm. All patients had surgical intervention to confirm EDx and US
      findings and had improved outcome on follow-up. CONCLUSION: These cases
      demonstrate the benefits of augmenting EDx with US by guiding accurate electrode
      localization and providing diagnostic information about lesion location.

PMID- 26206066
TI  - DNA nanopore translocation in glutamate solutions.
AB  - Nanopore experiments have traditionally been carried out with chloride-based
      solutions. Here we introduce silver/silver-glutamate-based electrochemistry as an
      alternative, and study the viscosity, conductivity, and nanopore translocation
      characteristics of potassium-, sodium-, and lithium-glutamate solutions. We show
      that it has a linear response at typical voltages and can be used to detect DNA
      translocations through a nanopore. The glutamate anion also acts as a redox
      capable thickening agent, with high-viscosity solutions capable of slowing down
      the DNA translocation process by up to 11 times, with a corresponding 7 time
      reduction in signal. These results demonstrate that glutamate can replace
      chloride as the primary anion in nanopore resistive pulse sensing. 

PMID- 26206067
TI  - Troponin elevation after black widow spider envenomation.
AB  - Black widow spider envenomation generally results in self-limiting pain that can
      be treated in the emergency department (ED) with analgesics and benzodiazepines,
      usually with no further intervention. Occasionally, a patient has to be admitted
      or treated with antivenom for refractory pain or a venom-induced complication. We
      present the case of an 84-year-old man who presented to our ED with chest pain
      and dyspnea after being bitten on the foot by a western black widow spider
      (Lactrodectus hesperus). His initial cardiac troponin I (cTnI) was elevated at
      0.07 ng/ml and continued to rise to a peak of 0.17 ng/ml. He also had
      rhabdomyolysis, another uncommon complication of black widow envenomation. An
      elevated cTnI generally signifies myocardial injury and is rarely seen after
      black widow envenomation. We discuss the possible etiologies for an elevated
      cardiac biomarker, in this context, and review potentially serious complications
      of widow spider envenomation presenting with chest symptoms and an elevated
      cardiac biomarker. 

PMID- 26206068
TI  - Dynamic model for controller design of condensate throttling systems.
AB  - Improving the load adjustment rate of coal-fired power plants in China is very
      important because of grid load fluctuations and the construction of new large
      scale power plants connected to the country's power grid. In this paper, a new
      application of condensate throttling system for rapid load adjustment is proposed
      on the basis of the characteristics of turbine-stored energy. To ensure effective
      and safe operation of the condensate throttling system, a non-linear control
      model is derived through reasonable simplifications of fundamental physical laws,
      and the model parameters are identified using experimental data from a 660 MW
      supercritical coal-fired power plant. The model outputs are compared with actual
      measured data for different unit loads. Results show that the established model's
      responses strongly correlate with the actual unit's responses and can be used for
      controller design.

PMID- 26206069
TI  - First Passaggio Transition Gestures in Classically Trained Female Singers.
AB  - OBJECTIVES/HYPOTHESIS: The purpose of this project was to determine the spectral
      and electroglottograph (EGG) differences exhibited by classically trained female
      singers when singing through their primo passaggio. The hypotheses were that the
      singers would exhibit relatively steady EGG levels and minimal changes in speech
      spectra when singing through their primo passaggio. It also was hypothesized that
      EGG and spectral measurements at the crest and trough of the vibrato cycles would
      be similar to each other. STUDY DESIGN: The study is an observational case
      control study. METHODS: Singers at training levels from undergraduate university
      students through professionals sang an A3-A4 scale using an /alpha:/ vowel while
      standing. Contact quotient (CQEGG), amplitudes of the first five harmonics (H1
      H5), and the number of the harmonics with greatest energy in the frequency region
      around 3000 Hz were measured at vibrato crests and troughs for each note.
      RESULTS: The data at the vibrato crests and troughs exhibited similar patterns
      across the notes that differed in the percentage CQEGG and harmonic amplitude.
      The mean CQEGG exhibited a slight decline from the lowest note to the highest,
      with a few of the singers exhibiting different patterns. The strongest harmonic
      for the four lowest notes was H3 with a transition to H2 being strongest for the
      four highest notes. CONCLUSIONS: The patterns of all the singers' averaged
      glottal and vocal tract adjustments through their primo passaggio generally
      followed what was hypothesized for the CQEGG, harmonic amplitudes, and harmonic
      of the frequency region around 3000 Hz. However, differences occurred between the
      measurements at the vibrato peaks and troughs.

PMID- 26206070
TI  - Dynamics of Glass Forming Liquids with Randomly Pinned Particles.
AB  - It is frequently assumed that in the limit of vanishing cooling rate, the glass
      transition phenomenon becomes a thermodynamic transition at a temperature TK.
      However, with any finite cooling rate, the system falls out of equilibrium at
      temperatures near Tg(>TK), implying that the very existence of the putative
      thermodynamic phase transition at TK can be questioned. Recent studies of systems
      with randomly pinned particles have hinted that the thermodynamic glass
      transition may be observed for liquids with randomly pinned particles. This
      expectation is based on the results of approximate calculations that suggest that
      the thermodynamic glass transition temperature increases with increasing
      concentration of pinned particles and it may be possible to equilibrate the
      system at temperatures near the increased transition temperature. We test the
      validity of this prediction through extensive molecular dynamics simulations of
      two model glass-forming liquids in the presence of random pinning. We find that
      extrapolated thermodynamic transition temperature TK does not show any sign of
      increasing with increasing pinning concentration. The main effect of pinning is
      found to be a rapid decrease in the kinetic fragility of the system with
      increasing pin concentration. Implications of these observations for current
      theories of the glass transition are discussed. 

PMID- 26206071
TI  - Determination of cholesterol oxides by gas chromatography-flame ionization
      detection/mass selective detection and their occurence in lanolin-containing
      cosmetics and ointments.
AB  - OBJECTIVE: Cholesterol oxides (COPs) are thought to be of toxicological relevance
      in cholesterol-containing foods. For cholesterol-containing cosmetics and the
      like, no information is available up to this date. Therefore, the first of two
      main aims of this study was to develop and validate a method for determining COPs
      in lanolin-containing cosmetics such as lipsticks and fatty creams as well as in
      nipple ointments. The second aim was to study the occurrence of COPs and their
      concentration levels in the respective product classes. METHODS: The procedure is
      based on a published method for food comprising some necessary modifications.
      Sample preparation consisted of transesterfication, solid-phase extraction and
      silylation of target compounds. Separation of the derivatized COPs and their
      quantification were performed with gas chromatography (GC) using a flame
      ionization detector (FID) or a mass spectrometer (MS). RESULTS: The successful
      validation and the trouble-free application during the market survey showed that
      the method was fit for purpose. Total COP levels found were in the low per cent
      range (up to 3%) and surprisingly high, being many orders of magnitude higher
      than those published for foods. CONCLUSION: To our knowledge, we present for the
      first time a method for the determination of COPs in non-food consumer products.
      Furthermore, our study demonstrates that lanolin-containing cosmetics may be an
      additional exogenous source of COPs. We further show evidence, that at least part
      of the COPs are already formed on the sheep's wool.

PMID- 26206072
TI  - Points to be considered when using transient elastography for diagnosis of portal
      hypertension according to the Baveno's VI consensus.

PMID- 26206073
TI  - Diabetes as a risk factor for hepatic encephalopathy in cirrhosis patients.
AB  - BACKGROUND & AIMS: It remains unclear whether diabetes increases the risk for
      hepatic encephalopathy (HE) in cirrhotic patients. We examined this question
      using data from three randomized trials of satavaptan, a vasopressin receptor
      antagonist that does not affect HE risk, in cirrhotic patients with ascites.
      METHODS: The trials included 1198 patients, and we excluded those with HE before
      or at randomization and followed the remaining patients for the one year duration
      of the trials. They were examined for HE regularly, and we compared rates of
      first-time overt HE between diabetics and non-diabetic patients using Cox
      regression, adjusting for gender, age, ascites severity, cirrhosis etiology,
      Child-Pugh class, creatinine, bilirubin, INR, sodium, potassium, albumin,
      platelets, lactulose use, benzodiazepine/barbiturate use, spironolactone dose,
      furosemide dose, potassium-sparing diuretic dose, and CirCom comorbidity score.
      RESULTS: We included 862 patients of whom 193 (22%) had diabetes. In total, they
      experienced 115 first-time episodes of overt HE during the follow-up. Fewer
      diabetics than non-diabetic patients were in Child-Pugh class C at baseline (13%
      vs. 23%), yet they had higher cumulative risk of first-time overt HE (26.0% vs.
      15.8% after 1 year), and their episodes of first-time overt HE were more likely
      to progress beyond grade 2 (64% vs. 42% of episodes progressed to grade 3 or 4,
      p=0.01 for independence between diabetes and highest HE grade). After the
      confounder adjustment, the hazard ratio of first-time overt HE for diabetics vs.
      non-diabetic patients was 1.86 (95% CI 1.20-2.87). CONCLUSIONS: Diabetes
      increased the risk of first-time overt HE among cirrhotic patients with ascites.

PMID- 26206074
TI  - CHRNA7 and CHRFAM7A mRNAs: co-localized and their expression levels altered in
      the postmortem dorsolateral prefrontal cortex in major psychiatric disorders.
AB  - OBJECTIVE: CHRNA7, coding alpha-7 nicotinic acetylcholine receptor (alpha7
      nAChR), is involved in cognition through interneuron modulation of dopamine and
      glutamate signaling. CHRNA7 and its partially duplicated chimeric gene CHRFAM7A
      have been implicated in schizophrenia through linkage and association studies.
      METHOD: Expression of CHRNA7 and CHRFAM7A mRNA was measured in the postmortem
      prefrontal cortex in more than 700 subjects, including patients with
      schizophrenia, bipolar disorder, major depression, and normal comparison
      subjects. The effects of antipsychotics and nicotine, as well as associations of
      CHRNA7 SNPs with gene expression, were explored. Fluorescent in-situ
      hybridization was used to examine coexpression of both transcripts in the human
      cortex. RESULTS: CHRFAM7A expression and CHRFAM7A/CHRNA7 ratios were higher in
      fetal compared with postnatal life, whereas CHRNA7 expression was relatively
      stable. CHRFAM7A expression was significantly elevated in all diagnostic groups,
      while CHRNA7 expression was reduced in the schizophrenia group and increased in
      the major depression group compared with the comparison group. CHRFAM7A/CHRNA7
      ratios were significantly increased in the schizophrenia and bipolar disorder
      groups compared with the comparison group. There was no effect of nicotine or
      antipsychotics and no association of SNPs in CHRNA7 with expression. CHRNA7 and
      CHRFAM7A mRNAs were expressed in the same neuronal nuclei of the human neocortex.
      CONCLUSIONS: These data show preferential fetal CHRFAM7A expression in the human
      prefrontal cortex and suggest abnormalities in the CHRFAM7A/CHRNA7 ratios in
      schizophrenia and bipolar disorder, due mainly to overexpression of CHRFAM7A.
      Given that these transcripts are coexpressed in a subset of human cortical
      neurons and can interact to alter function of nAChRs, these results support the
      concept of aberrant function of nAChRs in mental illness.

PMID- 26206075
TI  - Effect of Attention Training on Attention Bias Variability and PTSD Symptoms:
      Randomized Controlled Trials in Israeli and U.S. Combat Veterans.
AB  - OBJECTIVE: Attention allocation to threat is perturbed in patients with
      posttraumatic stress disorder (PTSD), with some studies indicating excess
      attention to threat and others indicating fluctuations between threat vigilance
      and threat avoidance. The authors tested the efficacy of two alternative
      computerized protocols, attention bias modification and attention control
      training, for rectifying threat attendance patterns and reducing PTSD symptoms.
      METHOD: Two randomized controlled trials compared the efficacy of attention bias
      modification and attention control training for PTSD: one in Israel Defense
      Forces veterans and one in U.S. military veterans. Both utilized variants of the
      dot-probe task, with attention bias modification designed to shift attention away
      from threat and attention control training balancing attention allocation between
      threat and neutral stimuli. PTSD symptoms, attention bias, and attention bias
      variability were measured before and after treatment. RESULTS: Both studies
      indicated significant symptom improvement after treatment, favoring attention
      control training. Additionally, both studies found that attention control
      training, but not attention bias modification, significantly reduced attention
      bias variability. Finally, a combined analysis of the two samples suggested that
      reductions in attention bias variability partially mediated improvement in PTSD
      symptoms. CONCLUSIONS: Attention control training may address aberrant
      fluctuations in attention allocation in PTSD, thereby reducing PTSD symptoms.
      Further study of treatment efficacy and its underlying neurocognitive mechanisms
      is warranted.

PMID- 26206076
TI  - Threat-Related Attention Bias Variability and Posttraumatic Stress.
AB  - OBJECTIVE: Threat monitoring facilitates survival by allowing one to efficiently
      and accurately detect potential threats. Traumatic events can disrupt healthy
      threat monitoring, inducing biased and unstable threat-related attention
      deployment. Recent research suggests that greater attention bias variability,
      that is, attention fluctuations alternating toward and away from threat, occurs
      in participants with PTSD relative to healthy comparison subjects who were either
      exposed or not exposed to traumatic events. The current study extends findings on
      attention bias variability in PTSD. METHOD: Previous measurement of attention
      bias variability was refined by employing a moving average technique. Analyses
      were conducted across seven independent data sets; in each, data on attention
      bias variability were collected by using variants of the dot-probe task. Trauma
      related and anxiety symptoms were evaluated across samples by using structured
      psychiatric interviews and widely used self-report questionnaires, as specified
      for each sample. RESULTS: Analyses revealed consistent evidence of greater
      attention bias variability in patients with PTSD following various types of
      traumatic events than in healthy participants, participants with social anxiety
      disorder, and participants with acute stress disorder. Moreover, threat-related,
      and not positive, attention bias variability was correlated with PTSD severity.
      CONCLUSIONS: These findings carry possibilities for using attention bias
      variability as a specific cognitive marker of PTSD and for tailoring protocols
      for attention bias modification for this disorder.

PMID- 26206077
TI  - Comparison between 5-day aprepitant and single-dose fosaprepitant meglumine for
      preventing nausea and vomiting induced by cisplatin-based chemotherapy.
AB  - PURPOSE: We aimed to compare the preventive effect of 5-day administration of
      aprepitant with single administration of fosaprepitant meglumine against nausea
      and vomiting symptoms due to highly emetogenic chemotherapy regimens comprising
      cisplatin (CDDP). METHODS: Subjects were inpatients who underwent chemotherapy
      for gastric cancer, esophageal cancer, lung cancer, or head and neck cancer with
      a regimen comprising 60 mg/m(2) or higher dose of CDDP. In this randomised, open
      label, controlled study, the subjects were assigned to a group given aprepitant
      for 5 days or a group given a single administration of fosaprepitant meglumine.
      The nausea and vomiting symptoms that emerged within 7 days after the first CDDP
      administration were investigated with a questionnaire form; the results were
      compared between the two groups. Risk factors affecting nausea and vomiting
      symptoms were also investigated. RESULTS: Of the 101 patients enrolled, 93
      patients were included (48 in the 5-day aprepitant group and 45 in the single
      fosaprepitant meglumine group). No significant intergroup differences in the
      complete response rate or the complete control rate were found over the entire
      period. The nausea score tended to increase from day 3 in both groups, but no
      significant intergroup difference was observed. Furthermore, the investigation of
      risk factors affecting moderate or severe nausea symptoms indicated that the
      fosaprepitant meglumine administration was not a risk factor. CONCLUSIONS: Single
      administration of fosaprepitant meglumine was not inferior to 5-day
      administration of aprepitant for preventing acute and delayed nausea and vomiting
      symptoms occurring after administration of CDDP (60 mg/m(2) or higher).

PMID- 26206078
TI  - All-or-(N)One - an epistemological characterization of the human tumorigenic
      neuronal paralogous FAM72 gene loci.
AB  - FAM72 is a novel neuronal progenitor cell (NPC) self-renewal supporting protein
      expressed under physiological conditions at low levels in other tissues.
      Accumulating data indicate the potential pivotal tumourigenic effects of FAM72.
      Our in silico human genome-wide analysis (GWA) revealed that the FAM72 gene
      family consists of four human-specific paralogous members, all of which are
      located on chromosome (chr) 1. Unique asymmetric FAM72 segmental gene
      duplications are most likely to have occurred in conjunction with the paired
      genomic neighbour SRGAP2 (SLIT-ROBO Rho GTPase activating protein), as both genes
      have four paralogues in humans but only one vertebra-emerging orthologue in all
      other species. No species with two or three FAM72/SRGAP2 gene pairs could be
      identified, and the four exclusively human-defining ohnologues, with different
      mutation patterns in Homo neanderthalensis and Denisova hominin, may remain under
      epigenetic control through long non-coding (lnc) RNAs. 

PMID- 26206079
TI  - Dynamics of chloroplast genomes in green plants.
AB  - Chloroplasts are essential organelles, in which genes have widely been used in
      the phylogenetic analysis of green plants. Here, we took advantage of the breadth
      of plastid genomes (cpDNAs) sequenced species to investigate their dynamic
      changes. Our study showed that gene rearrangements occurred more frequently in
      the cpDNAs of green algae than in land plants. Phylogenetic trees were generated
      using 55 conserved protein-coding genes including 33 genes for photosynthesis, 16
      ribosomal protein genes and 6 other genes, which supported the monophyletic
      evolution of vascular plants, land plants, seed plants, and angiosperms.
      Moreover, we could show that seed plants were more closely related to bryophytes
      rather than pteridophytes. Furthermore, the substitution rate for cpDNA genes was
      calculated to be 3.3*10(-10), which was almost 10 times lower than genes of
      nuclear genomes, probably because of the plastid homologous recombination
      machinery. 

PMID- 26206080
TI  - HCN4 mutation as a molecular explanation on patients with bradycardia and non
      compaction cardiomyopathy.
AB  - A very recent study suggested that HCN4 mutations could be associated with
      sinusal bradycardia and myocardial non compaction. A French family with 3
      affected sisters presenting the same clinical phenotype (sinus bradycardia in
      combination with non compaction cardiomyopathy (NCCM)) have benefited both from a
      systematic cardiovascular exploration and molecular investigations. The molecular
      analysis, performed by NGS sequencing, led to identify only one likely-disease
      causing variation: p.Gly482Arg on HCN4 gene. Our results confirm the genetic
      evidence for the involvement of the HCN4 mutations in the combined bradycardia
      NCCM phenotype and illustrates that, in front of this combined clinical
      phenotype, HCN4 mutations has to be suspected. 

PMID- 26206081
TI  - Oculo-auriculo-vertebral spectrum: clinical and molecular analysis of 51
      patients.
AB  - INTRODUCTION: Oculo-auriculo-vertebral spectrum (OAVS OMIM 164210) is a
      craniofacial developmental disorder affecting the development of the structures
      derived from the 1st and the 2nd branchial arches during embryogenesis, with
      consequential maxillary, mandibular, and ear abnormalities. The phenotype in OAVS
      is variable and associated clinical features can involve the cardiac, renal,
      skeletal, and central nervous systems. Its aetiology is still poorly understood.
      METHODS: We have evaluated the clinical phenotypes of 51 previously unpublished
      patients with OAVS and their parents, and performed comparative genomic
      hybridization microarray studies to identify potential causative loci. RESULTS:
      Of all 51 patients, 16 (31%) had a family history of OAVS. Most had no relevant
      pre-natal history and only 5 (10%) cases had a history of environmental exposures
      that have previously been described as risk factors for OAVS. In 28 (55%) cases,
      the malformations were unilateral. When the involvement was bilateral, it was
      asymmetric. Ear abnormalities were present in 47 (92%) patients (unilateral in
      24; and bilateral in 23). Hearing loss was common (85%), mostly conductive, but
      also sensorineural, or a combination of both. Hemifacial microsomia was present
      in 46 (90%) patients (17 also presented facial nerve palsy). Ocular anomalies
      were present in 15 (29%) patients. Vertebral anomalies were confirmed in 10 (20%)
      cases; 50% of those had additional heart, brain and/or other organ abnormalities.
      Brain abnormalities were present in 5 (10%) patients; developmental delay was
      more common among these patients. Limb abnormalities were found in 6 (12%)
      patients, and urogenital anomalies in 5 (10%). Array-CGH analysis identified
      22q11 dosage anomalies in 10 out of 22 index cases screened. DISCUSSION: In this
      study we carried out in-depth phenotyping of OAVS in a large, multicentre cohort.
      Clinical characteristics are in line with those reported previously, however, we
      observed a higher incidence of hemifacial microsomia and lower incidence of
      ocular anomalies. Furthermore our data suggests that OAVS patients with vertebral
      anomalies or congenital heart defects have a higher frequency of additional
      brain, limb or other malformations. We had a higher rate of familial cases in our
      cohort in comparison with previous reports, possibly because these cases were
      referred preferentially to our genetic clinic where family members underwent
      examination. We propose that familial OAVS cases show phenotypic variability,
      hence, affected relatives might have been misclassified in previous reports.
      Moreover, in view of its phenotypic variability, OAVS is potentially a spectrum
      of conditions, which overlap with other conditions, such as mandibulofacial
      dysostosis. Array CGH in our cohort identified recurrent dosage anomalies on
      22q11, which may contribute to, or increase the risk of OAVS. We hypothesize that
      although the 22q11 locus may harbour gene(s) or regulatory elements that play a
      role in the regulation of craniofacial symmetry and 1st and 2nd branchial arch
      development, OAVS is a heterogeneous condition and many cases have a
      multifactorial aetiology or are caused by mutations in as yet unidentified
      gene(s).

PMID- 26206083
TI  - MiR-539 inhibits thyroid cancer cell migration and invasion by directly targeting
      CARMA1.
AB  - MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and
      aberrant miRNA expression has been observed in thyroid cancer. However, the role
      of miRNAs in thyroid cancer metastasis remains largely unknown. In the current
      study, we found that miR-539 plays a suppressor role in thyroid cancer cell
      migration and invasion. Luciferase reporter assays confirmed that miR-539 binding
      to the 3'-UTR region of CARMA1 inhibited the expression of CARMA1 in thyroid
      cancer cells. Further studies demonstrated that CARMA1 can significantly promote
      the migration and invasion of thyroid cancer cells. Interestingly, overexpression
      or knockdown of CARMA1 effectively blocked the effect of miR-539 on the migration
      and invasion of thyroid cancer cells. Furthermore, we showed that miR-539
      expression was frequently downregulated and CARMA1 expression was significantly
      upregulated in thyroid cancer cell lines and thyroid cancer tissues compared with
      controls. Taken together, our data indicate that miR-539 is a novel regulator of
      migration and invasion in human thyroid cancer cells by targeting CARMA1. 

PMID- 26206082
TI  - Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF
      kappaB and PI3K/Akt3 signaling pathways.
AB  - Lipid raft proteins have been confirmed to be important in cell signal
      transduction. Some reports have shown that the aberrant expression of lipid raft
      proteins is associated with malignant phenotypes in some cancers. However, the
      role of the lipid raft protein flotillin-2 (Flot-2) in nasopharyngeal carcinoma
      (NPC) remains to be comprehensively characterized. Here, overexpression of Flot-2
      in NPC tissues and cell lines was detected by immunostaining, and Flot-2
      expression was found to be positively associated with NPC metastasis.
      Furthermore, inhibiting Flot-2 expression impaired the malignancy of the highly
      metastatic NPC cell line 5-8F by constraining its growth and proliferation,
      mobility and migration, and decreasing the capacity of 5-8F cells to metastasize
      in nude mice. In contrast, forced overexpression of Flot-2 increased the
      malignancy of 6-10B, a non-metastatic NPC cell line that weakly expresses Flot-2.
      Moreover, in 5-8F-shFlot-2 cells, which have inhibited Flot-2 expression, the NF
      kappaB and PI3K/Akt3 pathways were inactivated. Subsequently, MMPs expression
      were decreased, and Foxo1 activity was increased. In addition, enhanced NF-kappaB
      and PI3K/Akt3 activities were observed in Flot-2 overexpressing 6-10B cells.
      Thus, Flot-2 exerts a pro-neoplastic role in NPC and is involved in tumor
      progression and metastasis. Moreover, Flot-2 exerts its role through NF-kappaB
      and PI3K/Akt3 signaling. 

PMID- 26206084
TI  - Structural basis for the ligand-binding specificity of fatty acid-binding
      proteins (pFABP4 and pFABP5) in gentoo penguin.
AB  - Fatty acid-binding proteins (FABPs) are involved in transporting hydrophobic
      fatty acids between various aqueous compartments of the cell by directly binding
      ligands inside their beta-barrel cavities. Here, we report the crystal structures
      of ligand-unbound pFABP4, linoleate-bound pFABP4, and palmitate-bound pFABP5,
      obtained from gentoo penguin (Pygoscelis papua), at a resolution of 2.1 A, 2.2 A,
      and 2.3 A, respectively. The pFABP4 and pFABP5 proteins have a canonical beta
      barrel structure with two short alpha-helices that form a cap region and fatty
      acid ligand binding sites in the hydrophobic cavity within the beta-barrel
      structure. Linoleate-bound pFABP4 and palmitate-bound pFABP5 possess different
      ligand-binding modes and a unique ligand-binding pocket due to several sequence
      dissimilarities (A76/L78, T30/M32, underlining indicates pFABP4 residues) between
      the two proteins. Structural comparison revealed significantly different
      conformational changes in the beta3-beta4 loop region (residues 57-62) as well as
      the flipped Phe60 residue of pFABP5 than that in pFABP4 (the corresponding
      residue is Phe58). A ligand-binding study using fluorophore displacement assays
      shows that pFABP4 has a relatively strong affinity for linoleate as compared to
      pFABP5. In contrast, pFABP5 exhibits higher affinity for palmitate than that for
      pFABP4. In conclusion, our high-resolution structures and ligand-binding studies
      provide useful insights into the ligand-binding preferences of pFABPs based on
      key protein-ligand interactions. 

PMID- 26206085
TI  - Chromatin organization in pluripotent cells: emerging approaches to study and
      disrupt function.
AB  - Translating the vast amounts of genomic and epigenomic information accumulated on
      the linear genome into three-dimensional models of nuclear organization is a
      current major challenge. In response to this challenge, recent technological
      innovations based on chromosome conformation capture methods in combination with
      increasingly powerful functional approaches have revealed exciting insights into
      key aspects of genome regulation. These findings have led to an emerging model
      where the genome is folded and compartmentalized into highly conserved
      topological domains that are further divided into functional subdomains
      containing physical loops that bring cis-regulatory elements to close proximity.
      Targeted functional experiments, largely based on designable DNA-binding
      proteins, have begun to define the major architectural proteins required to
      establish and maintain appropriate genome regulation. Here, we focus on the
      accessible and well-characterized system of pluripotent cells to review the
      functional role of chromatin organization in regulating pluripotency,
      differentiation and reprogramming. 

PMID- 26206087
TI  - Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner.
AB  - In multicellular organisms, a tight control of cell death is required to ensure
      normal development and tissue homeostasis. Improper function of apoptotic or
      survival pathways can not only affect developmental programs but also favor
      cancer progression. Here we describe a novel apoptotic signaling pathway
      involving the transmembrane receptor Kremen1 and its ligand, the Wnt-antagonist
      Dickkopf1. Using a whole embryo culture system, we first show that Dickkopf1
      treatment promotes cell survival in a mouse model exhibiting increased apoptosis
      in the developing neural plate. Remarkably, this effect was not recapitulated by
      chemical Wnt inhibition. We then show that Dickkopf1 receptor Kremen1 is a bona
      fide dependence receptor, triggering cell death unless bound to its ligand. We
      performed Wnt-activity assays to demonstrate that the pro-apoptotic and anti-Wnt
      functions mediated by Kremen1 are strictly independent. Furthermore, we combined
      phylogenetic and mutagenesis approaches to identify a specific motif in the
      cytoplasmic tail of Kremen1, which is (i) specifically conserved in the lineage
      of placental mammals and (ii) strictly required for apoptosis induction. Finally,
      we show that somatic mutations of kremen1 found in human cancers can affect its
      pro-apoptotic activity, supporting a tumor suppressor function. Our findings thus
      reveal a new Wnt-independent function for Kremen1 and Dickkopf1 in the regulation
      of cell survival with potential implications in cancer therapies. 

PMID- 26206086
TI  - The SR/ER-mitochondria calcium crosstalk is regulated by GSK3beta during
      reperfusion injury.
AB  - Glycogen synthase kinase-3beta (GSK3beta) is a multifunctional kinase whose
      inhibition is known to limit myocardial ischemia-reperfusion injury. However, the
      mechanism mediating this beneficial effect still remains unclear. Mitochondria
      and sarco/endoplasmic reticulum (SR/ER) are key players in cell death signaling.
      Their involvement in myocardial ischemia-reperfusion injury has gained
      recognition recently, but the underlying mechanisms are not yet well understood.
      We questioned here whether GSK3beta might have a role in the Ca(2+) transfer from
      SR/ER to mitochondria at reperfusion. We showed that a fraction of GSK3beta
      protein is localized to the SR/ER and mitochondria-associated ER membranes (MAMs)
      in the heart, and that GSK3beta specifically interacted with the inositol 1,4,5
      trisphosphate receptors (IP3Rs) Ca(2+) channeling complex in MAMs. We
      demonstrated that both pharmacological and genetic inhibition of GSK3beta
      decreased protein interaction of IP3R with the Ca(2+) channeling complex,
      impaired SR/ER Ca(2+) release and reduced the histamine-stimulated Ca(2+)
      exchange between SR/ER and mitochondria in cardiomyocytes. During hypoxia
      reoxygenation, cell death is associated with an increase of GSK3beta activity and
      IP3R phosphorylation, which leads to enhanced transfer of Ca(2+) from SR/ER to
      mitochondria. Inhibition of GSK3beta at reperfusion reduced both IP3R
      phosphorylation and SR/ER Ca(2+) release, which consequently diminished both
      cytosolic and mitochondrial Ca(2+) concentrations, as well as sensitivity to
      apoptosis. We conclude that inhibition of GSK3beta at reperfusion diminishes
      Ca(2+) leak from IP3R at MAMs in the heart, which limits both cytosolic and
      mitochondrial Ca(2+) overload and subsequent cell death. 

PMID- 26206088
TI  - Phosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase
      and its dysregulation is implicated in neurodegenerative diseases. Likewise, C
      terminus of Hsc70-interacting protein (CHIP) is linked to neurological disorders,
      serving as an E3 ubiquitin ligase for targeting damaged or toxic proteins for
      proteasomal degradation. Here, we demonstrate that CHIP is a novel substrate for
      Cdk5. Cdk5 phosphorylates CHIP at Ser20 via direct binding to a highly charged
      domain of CHIP. Co-immunoprecipitation and ubiquitination assays reveal that Cdk5
      mediated phosphorylation disrupts the interaction between CHIP and truncated
      apoptosis-inducing factor (tAIF) without affecting CHIP's E3 ligase activity,
      resulting in the inhibition of CHIP-mediated degradation of tAIF. Lentiviral
      transduction assay shows that knockdown of Cdk5 or overexpression of CHIP(S20A),
      but not CHIP(WT), attenuates tAIF-mediated neuronal cell death induced by
      hydrogen peroxide. Thus, we conclude that Cdk5-mediated phosphorylation of CHIP
      negatively regulates its neuroprotective function, thereby contributing to
      neuronal cell death progression following neurotoxic stimuli. 

PMID- 26206089
TI  - miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast
      differentiation and enhances bone formation, by regulating c-Cbl-mediated
      PI3K/AKT pathway.
AB  - Osteoporosis is a disease marked by reduced bone mass, leading to an increased
      risk of fractures or broken bones. Bone formation is mediated by recruiting
      mesenchymal stem cells (MSCs). Elucidation of the molecular mechanisms that
      regulate MSC differentiation into osteoblasts is of great importance for the
      development of anabolic therapies for osteoporosis and other bone metabolism
      related diseases. microRNAs (miRNAs) have been reported to have crucial roles in
      bone development, osteogenic differentiation and osteoporosis pathophysiology.
      However, to date, only a few miRNAs have been reported to enhance osteogenesis
      and regulate the suppressive effect of glucocorticoids on osteogenic
      differentiation. In this study, we discovered that miR-216a, a pancreatic
      specific miRNA, was significantly upregulated during osteogenic differentiation
      in human adipose-derived MSCs (hAMSCs). The expression of miR-216a was positively
      correlated with the expression of bone formation marker genes in clinical
      osteoporosis samples. Functional analysis demonstrated that miR-216a can markedly
      promote osteogenic differentiation of hAMSCs, rescue the suppressive effect of
      dexamethasone (DEX) on osteogenic differentiation in vitro and enhance bone
      formation in vivo. c-Cbl, a gene that encodes a RING finger E3 ubiquitin ligase,
      was identified as a direct target of miR-216a. Downregulation of c-Cbl by short
      hairpin RNAs can mimic the promotion effects of miR-216a and significantly rescue
      the suppressive effects of DEX on osteogenesis. Pathway analysis indicated that
      miR-216a regulation of osteogenic differentiation occurs via the c-Cbl-mediated
      phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The recovery effects of miR
      216a on the inhibition of osteogenesis by DEX were attenuated after blocking the
      PI3K pathway. Thus, our findings suggest that miR-216a may serve as a novel
      therapeutic agent for the prevention and treatment of osteoporosis and other bone
      metabolism-related diseases. 

PMID- 26206090
TI  - RNASET2 is required for ROS propagation during oxidative stress-mediated cell
      death.
AB  - RNASET2 is a ubiquitously expressed acidic ribonuclease that has been implicated
      in diverse pathophysiological processes including tumorigeneis, vitiligo,
      asthenozoospermia, and neurodegeneration. Prior studies indicate that RNASET2 is
      induced in response to oxidative stress and that overexpression of RNASET2
      sensitizes cells to reactive oxygen species (ROS)-induced cell death through a
      mechanism that is independent of catalytic activity. Herein, we report a loss-of
      function genetic screen that identified RNASET2 as an essential gene for
      lipotoxic cell death. Haploinsufficiency of RNASET2 confers increased antioxidant
      capacity and generalized resistance to oxidative stress-mediated cell death in
      cultured cells. This function is critically dependent on catalytic activity.
      Furthermore, knockdown of RNASET2 in the Drosophila fat body confers increased
      survival in the setting of oxidative stress inducers. Together, these findings
      demonstrate that RNASET2 regulates antioxidant tone and is required for
      physiological ROS responses. 

PMID- 26206092
TI  - Diabetes Mellitus in Saudi Arabia: A Review of the Recent Literature.
AB  - The World Health Organization (WHO) has reported that Saudi Arabia ranks the
      second highest in the Middle East, and is seventh in the world for the rate of
      diabetes. It is estimated that around 7 million of the population are diabetic
      and almost around 3 million have pre-diabetes. Even more worrying perhaps, is the
      increasing pattern of diabetes noted in Saudi Arabia in the recent past. In fact,
      diabetes has approximately registered a ten-fold increase in the past three eras
      in Saudi Arabia. Diabetes mellitus (DM) has been found to be related to high
      mortality, morbidity and vascular complications, accompanied by poor general
      health and lower quality of life. In Saudi Arabia, DM is quickly reaching
      disturbing proportions and becoming a significant cause of medical complications
      and even death. However, when compared with the developed countries, the research
      work conducted, focusing particularly on the incidence, prevalence and socio
      demographic properties of DM is woefully inadequate. The health burden due to DM
      in Saudi Arabia is predicted to rise to catastrophic levels, unless a wide
      ranging epidemic control program is incorporated, with great emphasis laid on
      advocating a healthy diet, including exercise and active lifestyles, and weight
      control. To properly manage the DM in Saudi Arabia, a multidisciplinary approach
      is required. In this review we discuss all the aspects of DM in Saudi Arabia
      drawing from the published literature currently available.

PMID- 26206091
TI  - Reduced mitochondrial Ca(2+) transients stimulate autophagy in human fibroblasts
      carrying the 13514A>G mutation of the ND5 subunit of NADH dehydrogenase.
AB  - Mitochondrial disorders are a group of pathologies characterized by impairment of
      mitochondrial function mainly due to defects of the respiratory chain and
      consequent organellar energetics. This affects organs and tissues that require an
      efficient energy supply, such as brain and skeletal muscle. They are caused by
      mutations in both nuclear- and mitochondrial DNA (mtDNA)-encoded genes and their
      clinical manifestations show a great heterogeneity in terms of age of onset and
      severity, suggesting that patient-specific features are key determinants of the
      pathogenic process. In order to correlate the genetic defect to the clinical
      phenotype, we used a cell culture model consisting of fibroblasts derived from
      patients with different mutations in the mtDNA-encoded ND5 complex I subunit and
      with different severities of the illness. Interestingly, we found that cells from
      patients with the 13514A>G mutation, who manifested a relatively late onset and
      slower progression of the disease, display an increased autophagic flux when
      compared with fibroblasts from other patients or healthy donors. We characterized
      their mitochondrial phenotype by investigating organelle turnover, morphology,
      membrane potential and Ca(2+) homeostasis, demonstrating that mitochondrial
      quality control through mitophagy is upregulated in 13514A>G cells. This is due
      to a specific downregulation of mitochondrial Ca(2+) uptake that causes the
      stimulation of the autophagic machinery through the AMPK signaling axis. Genetic
      and pharmacological manipulation of mitochondrial Ca(2+) homeostasis can revert
      this phenotype, but concurrently decreases cell viability. This indicates that
      the higher mitochondrial turnover in complex I deficient cells with this specific
      mutation is a pro-survival compensatory mechanism that could contribute to the
      mild clinical phenotype of this patient. 

PMID- 26206093
TI  - The Impact of Diabetes on Mortality Among Elderly Patients Admitted for Treatment
      at a Hospital for Cardiovascular Disease in Southern Brazil.
AB  - BACKGROUND: Diabetes has been shown to be associated with increased mortality and
      morbidity worldwide. This study explored whether diabetes significantly impacts
      on outcomes among elderly adults with cardiovascular disease (CVD) admitted to a
      specialist hospital in Southern Brazil. DESIGN: A prospective cohort study of 411
      patients admitted to hospital after a cardiac event between 2008 and 2010.
      METHODS: The primary end point was death by all causes during the follow up
      period of 6 months from admission. All hospital death reports matched those
      reported by the Brazilian Public Health Death Records. Cumulative probability of
      survival by Kaplan-Meier plot and log rank tests compared hospital admissions
      with or without diabetes. Adjusted and unadjusted hazard ratios (HR) for overall
      mortality were calculated. RESULTS AND CONCLUSIONS: The mean +/- SD age of the
      subjects was 69.8 years +/- 14 and 50% were men. Overall study mortality was
      8.7%. Half of the deaths occurred in patients &#8805;80 years (p=0.001). Diabetes
      was associated with 53% of the overall mortality (p<0.01) and 79% of the CVD
      related deaths (p<0.03). The adjusted HR was 2.88 (95% CI 1.42-5.84) for diabetic
      patients aged &#8805;80 years. In conclusion, the results suggest that elderly
      patients of European origin with diabetes residing in Southern Brazil admitted to
      hospital for specialist CVD treatment have poorer survival and higher risk of
      further CVD events 6 months after hospital discharge compared with those without.
      We recommend that better strategies for managing CVD risk factors among elderly
      diabetic patients from similar patient cohorts in Brazil are necessary.

PMID- 26206094
TI  - Serum Zinc and &#946; D Glucuronidase Enzyme Level in Type 2 Diabetes Mellitus
      with Periodontitis.
AB  - The exact mechanism by which nutritional deficiency and lysosomal enzyme change,
      modify periodontal destruction has not yet been precisely defined. The study
      aimed to determine the serum zinc and beta D glucuronidase enzyme level in the
      selected groups and how its increase or decrease levels are related to type 2
      diabetes mellitus (T2DM) with periodontitis when compared to other groups. Six
      hundred subjects were selected and are categorized into four groups as Group I
      (control healthy subjects, n=150), Group II (T2DM with periodontitis, n=150),
      Group III (T2DM without periodontitis, n=150) and Group IV (Non-DM with
      periodontitis, n=150). The lab investigations included measuring fasting blood
      glucose, serum zinc and beta D- glucuronidase levels. In the results, the level
      of serum zinc was found to be lesser in group III subjects and the activity of
      serum beta D glucuronidase was found to be elevated nine times in group III (T2DM
      with periodontitis) and two times elevated in group II (T2DM without
      periodontitis) and group IV (Non-DM with periodontitis), when compared to
      control. Zinc has been reported to reduce the stabilization of lysosomal
      membranes. Periodontitis has been taken as the prime condition in this study and
      categorized as experimental groups. Perturbations in mineral metabolism are more
      pronounced in diabetic populations. When the level of zinc is decreased, the
      structural integrity of lysosomal membrane has been lost and it would have caused
      for the increased release of beta D glucuronidase in T2DM with periodontitis.

PMID- 26206095
TI  - Effect of vitamin D supplementation on selected inflammatory biomarkers in older
      adults: a secondary analysis of data from a randomised, placebo-controlled trial.
AB  - Observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels
      are associated with inflammatory markers. Most trials reporting significant
      associations between vitamin D intake and inflammatory markers used specific
      patient groups. Thus, we aimed to determine the effect of supplementary vitamin D
      using secondary data from a population-based, randomised, placebo-controlled,
      double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84
      year-old residents of one of the four eastern states of Australia. They were
      randomly selected from the electoral roll and were randomised to one of three
      trial arms: placebo (n 214), 750 MUg (n 215) or 1500 MUg (n 215) vitamin D3, each
      taken once per month for 12 months. Post-intervention blood samples for the
      analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels
      were available for 613 participants. Associations between intervention group and
      biomarker levels were evaluated using quantile regression. There were no
      statistically significant differences in distributions of CRP, leptin,
      adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group
      and either supplemented group. The 75th percentile IL-6 level was 2.8 pg/ml
      higher (95 % CI 0.4, 5.8 pg/ml) in the 1500 MUg group than in the placebo group
      (75th percentiles:11.0 v. 8.2 pg/ml), with a somewhat smaller, non-significant
      difference in 75th percentiles between the 750 MUg and placebo groups. Despite
      large differences in serum 25(OH)D levels between the three groups after 12
      months of supplementation, we found little evidence of an effect of vitamin D
      supplementation on cytokine or adipokine levels, with the possible exception of
      IL-6. 

PMID- 26206096
TI  - Carbamazepine as a Treatment for Trigeminal Trophic Syndrome: A Case Report and
      Literature Review.

PMID- 26206097
TI  - Diagnosis and Treatment of Eclamptic Psychosis in the Postpartum Period: A Case
      Report.

PMID- 26206098
TI  - Dynamic Coupling of Iron, Manganese, and Phosphorus Behavior in Water and
      Sediment of Shallow Ice-Covered Eutrophic Lakes.
AB  - Decreasing duration and occurrence of northern hemisphere ice cover due to recent
      climate warming is well-documented; however, biogeochemical dynamics underneath
      the ice are poorly understood. We couple time-series analyses of water column and
      sediment water interface (SWI) geochemistry with hydrodynamic data to develop a
      holistic model of iron (Fe), manganese (Mn), and phosphorus (P) behavior
      underneath the ice of a shallow eutrophic freshwater bay. During periods of
      persistent subfreezing temperatures, a highly reactive pool of dissolved and
      colloidal Fe, Mn, and P develops over time in surface sediments and bottom waters
      due to reductive dissolution of Fe/Mn(oxy)hydroxides below the SWI. Redox
      dynamics are driven by benthic O2 consumption, limited air-water exchange of
      oxygen due to ice cover, and minimal circulation. During thaw events, the
      concentration, distribution and size partitioning of all species changes, with
      the highest concentrations of P and "truly dissolved" Fe near the water column
      surface, and a relatively well-mixed "truly dissolved" Mn and "colloidal" Fe
      profile due to the influx of geochemically distinct river water and increased
      circulation. The partitioning and flux of trace metals and phosphorus beneath the
      ice is dynamic, and heavily influenced by climate-dependent physical processes
      that vary in both time and space.

PMID- 26206099
TI  - Synergy of molecular targeted approaches and immunotherapy in melanoma:
      preclinical basis and clinical perspectives.
AB  - INTRODUCTION: Targeted therapy and immunotherapies are the novel pharmacologic
      treatment strategies for metastatic melanoma. BRAF and MEK inhibitors effectively
      block the hyperactivation of the MAPK pathway in BRAF mutant melanomas and also
      have several other effects on melanoma cells and on the immune response. The aim
      of this work is to discuss the rationale, evidence and perspectives of approaches
      combining target and immunotherapy against melanoma. AREAS COVERED: We first
      review the effects of BRAF and MEK inhibitors on melanoma cells and on the
      different components of the immune system. Afterwards, we summarize the results
      of the preclinical and clinical studies that have combined targeted therapy and
      immunotherapy for the treatment of melanoma. EXPERT OPINION: Clinical
      applications of immunotherapy strategies have recently changed the therapeutic
      mainstay for metastatic melanoma. Biologic and initial preclinical data support
      their integration with innovative molecular targeted therapies, opening enormous
      perspectives for researchers in the effort of finding a definitive cure. Main
      open challenges are the definition of reliable research models, assessment of
      effective schedules, safety issues and designing of personalized approaches.

PMID- 26206100
TI  - Evaluation of an heterogeneous group of patients with von Willebrand disease
      using an assay alternative to ristocetin induced platelet agglutination.
AB  - BACKGROUND: Diagnosis of von Willebrand disease (VWD) type 2 usually relies on
      the discrepancy between the von Willebrand factor (VWF) ristocetin cofactor
      activity (VWF:RCo) and VWF antigen (VWF:Ag). Type 2B patients can be
      discriminated from other qualitative VWD variants by using ristocetin-induced
      platelet agglutination (RIPA) test. The major limitation of RIPA is the
      requirement of fresh blood sample. OBJECTIVES: In this study, we evaluated the
      VWF gain-of-function mutant GPIb binding (VWF:GPIbM) and VWF:RCo assays to
      investigate whether the VWF:GPIbM/VWF:RCo ratio was able to identify the type 2B
      variant among an heterogeneous VWD population, previously characterized following
      the ISTH-SSC guidelines. PATIENTS/METHODS: Seventy-six VWD patients and 31
      healthy subjects were evaluated by using VWF:Ag, VWF:RCo, and VWF:GPIbM assays.
      RESULTS: The mean (minimum-maximum values) VWF:GPIbM/VWF:RCo ratio was higher in
      type 2B patients (2.53, 0.84-6.11) than in healthy controls (1.05, 0.87-1.34),
      type 1 (0.85, 0.51-1.15), 2A (1.20, 0.36-2.82), and 2M (1.07, 0.91-1.38) (P <
      0.0001). Type 2B variants were divided into four groups (A, B, C, and D)
      according to their different multimeric patterns. The mean value of the
      VWF:GPIbM/VWF:RCo ratio in the four groups showed an increasing trend from group
      A (1.08) to D (3.69), proportional to the loss of high molecular weight
      multimers. Among 32 type 2B patients, previously diagnosed with RIPA, 8 (mainly
      with a type I New York/Malmo phenotype) were not confirmed using the
      VWF:GPIbM/VWF:RCo ratio. CONCLUSIONS: Whenever the RIPA test is not feasible, the
      VWF:GPIbM/VWF:RCo ratio might help to identify severe type 2B VWD patients.

PMID- 26206101
TI  - [Ethical problems raised by new reproductive biotechnologies and stem cells].
AB  - Research about the hormonal mechanisms controlling reproduction in mammals has
      soared during the first half of the 20th century. It has produced a series of
      discoveries with important outcomes, not only scientific, but also impacting the
      ways of life. Besides the advent of the contraceptive pill, it has permitted to
      isolate and cultivate in vitro the female gamete, to fertilize it, thus obtaining
      a zygote that continues to develop until the blastocyst stage outside the
      maternal organism. The embryo, transferred into a foster-mother, develops
      normally until term: the first "test-tube baby" was born in this way in 1978. But
      the only fact of being able to cultivate the human egg in vitro was to open other
      possibilities and allow further biological advances: embryonic stem cells (ES
      cells) obtained from blastocysts and, more recently, from induced Pluripotent
      Stem cells (iPS), which can potentially be derived from all types of
      differentiated cell types obtained from adult individuals. From then on, the
      advent of a new medicine could be anticipated, regenerative because able to
      replace deficient or absent cells within the organism. As each of these steps was
      reached, scientists have encountered vigorous opposition from the people: the new
      potentials disturbed the conceptions that man had of his relationship to nature,
      in particular in two sensitive domains: sexuality and reproduction. The progress
      of science has however been accepted by most as soon as it was understood that
      humanity could anticipate advantages from these advances. 

PMID- 26206102
TI  - [What to do with brain imaging? Old and new territories of a technology].
AB  - During the twentieth century, brain imaging revolutionized neurological practice
      and research in cognitive neuroscience. More recently, its scope has moved from
      the former territories to the humanities. After describing this historical
      dynamic, some issues and controversies related to old and new uses of
      neuroimaging are recalled, and this new appetite for brain image is questioned. 

PMID- 26206103
TI  - The influence of physician recommendation on prostate-specific antigen screening.
AB  - PURPOSE: Prostate-specific antigen (PSA) screening is controversial, and little
      is known regarding a physician's effect on a patient's decision to undergo
      screening. This study's objective was to evaluate the effect of a patient's
      understanding of the risks and benefits of screening compared to the final
      recommendation of the provider on the patient's decision to undergo PSA
      screening. MATERIALS AND METHODS: Using the 2012 Behavioral Risk Factor
      Surveillance System, men older than 55 years who did not have a history of
      prostate cancer/prostate "problem" and who reported a PSA test within the
      preceding year were considered to have undergone screening. The percentages of
      men informed and not informed of the risks and benefits of screening and the
      percentage men receiving recommendations for PSA screening from their provider
      were reported. Multivariable complex-sample logistic regression calculated the
      odds of undergoing screening. RESULTS: In all, 75% of men were informed of
      screening benefits; however, 32% were informed of screening risks. After being
      informed of both, 56% of men opted for PSA screening if the provider recommended
      it, compared with only 21% when not recommended. Men receiving a recommendation
      to undergo PSA testing had higher odds of undergoing screening (odds ratio [OR] =
      4.98, 95% CI: 4.53-5.48) compared with those who were only informed about
      screening benefits (OR = 2.40, 95% CI: 2.18-2.65) or risks (OR = 0.92, 95% CI:
      0.86-0.98). Significant limitations include recall and nonresponse bias.
      CONCLUSIONS: Patients' decision to undergo or forgo PSA screening is heavily
      influenced by the recommendation of their physician; it is imperative that
      physicians are cognizant of their biases and facilitate a shared decision-making
      process.

PMID- 26206104
TI  - Surgical management of bladder urothelial carcinoma with squamous
      differentiation.
AB  - BACKGROUND: Urothelial carcinoma (UC) with squamous differentiation (UC w/SD) is
      the most common variant bladder cancer histology. MAIN FINDINGS: Accurate
      identification at the time of transurethral resection is critical although
      current barriers exist, which include tumor heterogeneity, sampling limitation
      during resection, and pathologic interpretation of specimens. Although many cases
      of UC w/SD present with muscle-invasive bladder cancer, those cancers that are
      confirmed to be truly non-muscle invasive can be managed with endoscopic
      resection, adjuvant intravesical therapies (i.e., Bacillus Calmitte Guerin), and
      close surveillance. Radical cystectomy series suggest that UC w/SD tends to
      present at a more advanced stage than pure UC does although survival outcomes are
      similar when controlling for standard clinicopathologic factors. PRINCIPAL
      CONCLUSIONS: Future basic science and clinical studies are requisite to better
      investigate the biology of urothelial carcinoma with squamous differentiation and
      response to multimodal therapies.

PMID- 26206106
TI  - Regulatory T cells in immune-mediated renal disease.
AB  - Regulatory T cells (Tregs) are CD4+ T cells that can suppress immune responses by
      effector T cells, B cells and innate immune cells. This review discusses the role
      that Tregs play in murine models of immune-mediated renal diseases and acute
      kidney injury and in human autoimmune kidney disease (such as systemic lupus
      erythematosus, anti-glomerular basement membrane disease, anti-neutrophil
      cytoplasmic antibody-associated vasculitis). Current research suggests that Tregs
      may be reduced in number and/or have impaired regulatory function in these
      diseases. Tregs possess several mechanisms by which they can limit renal and
      systemic inflammatory immune responses. Potential therapeutic applications
      involving Tregs include in vivo induction of Tregs or inducing Tregs from naive
      CD4+ T cells or expanding natural Tregs ex vivo, to use as a cellular therapy. At
      present, the optimal method of generating a phenotypically stable pool of Tregs
      with long-lasting suppressive effects is not established, but human studies in
      renal transplantation are underway exploring the therapeutic potential of Tregs
      as a cellular therapy, and if successful may have a role as a novel therapy in
      immune-mediated renal diseases. 

PMID- 26206107
TI  - Magneto-immunocapture with on-bead fluorescent labeling of amyloid-beta peptides:
      towards a microfluidized-bed-based operation.
AB  - A new sample treatment approach for sensitive determination of three amyloid-beta
      peptides (Abeta 1-42, Abeta 1-40 and Abeta 1-38) with capillary electrophoresis
      coupled with laser induced fluorescent detection is reported herein. These Abeta
      peptides are considered an important family of biomarkers in the cerebrospinal
      fluid (CSF) for early diagnosis of Alzheimer's disease (AD). Due to their
      extremely low abundance in CSF (down to sub nM ranges), batch-wise
      preconcentration via magneto-immunocapture with enrichment factors up to 100 was
      implemented. The Abeta peptides were first captured onto magnetic micro-beads.
      Then, on-beads fluorescent labeling of the captured Abeta peptides were carried
      out to avoid the unwanted presence of extra fluorescent dye in the eluent as in
      the case of in-solution labeling. Finally thermal elution was performed and
      eluted labeled peptides were analyzed off line with CE-LIF. The Abeta-capturing
      efficiencies of different commercially available antibodies grafted onto magnetic
      beads were tested. Abeta peptides in CSF samples collected from AD's patients and
      healthy persons (used as controls) were measured and evaluated. As a proof of
      concept, the developed strategy was adapted into a miniaturized fluidized bed
      configuration that has the potential for coupling with a microchip separation
      system. 

PMID- 26206105
TI  - Reciprocal Control of Osteogenic and Adipogenic Differentiation by ERK/MAP Kinase
      Phosphorylation of Runx2 and PPARgamma Transcription Factors.
AB  - In many skeletal diseases, including osteoporosis and disuse osteopenia,
      defective osteoblast differentiation is associated with increased marrow
      adipogenesis. The relative activity of two transcription factors, RUNX2 and
      PPARgamma, controls whether a mesenchymal cell will differentiate into an
      osteoblast or adipocyte. Herein we show that the ERK/MAP kinase pathway, an
      important mediator of mechanical and hormonal signals in bone, stimulates
      osteoblastogenesis and inhibits adipogenesis via phosphorylation of RUNX2 and
      PPARgamma. Induction of osteoblastogenesis in ST2 mesenchymal cells was
      associated with increased MAPK activity and RUNX2 phosphorylation. Under these
      conditions PPARgamma phosphorylation also increased, but adipogenesis was
      inhibited. In contrast, during adipogenesis MAPK activity and phosphorylation of
      both transcription factors was reduced. RUNX2 phosphorylation and transcriptional
      activity were directly stimulated by MAPK, a response requiring phosphorylation
      at S301 and S319. MAPK also inhibited PPARgamma-dependent transcription via S112
      phosphorylation. Stimulation of MAPK increased osteoblastogenesis and inhibited
      adipogenesis, while dominant-negative suppression of activity had the opposite
      effect. In rescue experiments using Runx2(-/-) mouse embryo fibroblasts (MEFs),
      wild type or, to a greater extent, phosphomimetic mutant RUNX2 (S301E,S319E)
      stimulated osteoblastogenesis while suppressing adipogenesis. In contrast, a
      phosphorylation-deficient RUNX2 mutant (S301A,S319A) had reduced activity.
      Conversely, wild type or, to a greater extent, phosphorylation-resistant S112A
      mutant PPARgamma strongly stimulated adipogenesis and inhibited
      osteoblastogenesis in Pparg(-/-) MEFs, while S112E mutant PPARgamma was less
      active. Competition between RUNX2 and PPARgamma was also observed at the
      transcriptional level. Together, these studies highlight the importance of MAP
      kinase signaling and RUNX2/PPARgamma phosphorylation in the control of osteoblast
      and adipocyte lineages.

PMID- 26206108
TI  - Risk factors for the development of psychopathology following trauma.
AB  - Traumatic experiences can lead to a range of mental health problems with
      posttraumatic stress disorder (PTSD) leading as the most documented disorder
      following trauma. Epidemiological research has found the rate of exposure to
      trauma to far outweigh the prevalence of PTSD. Indicating that most people do not
      develop PTSD following a traumatic event, this phenomenon has led to an interest
      in evaluating risk factors to determine who develops PTSD. Risk factors for the
      development of psychopathology following trauma exposure fall into three
      categories: pre-trauma, peri-trauma and post-trauma factors. Pre-trauma factors
      can include age, gender, race/ethnicity, education, prior psychopathology, and
      neurobiological factors. Peri-trauma factors can include the duration/severity of
      trauma experience and the perception that the trauma has ended. Post-trauma
      factors can include access to needed resources, social support, specific
      cognitive patterns, and physical activity. To date, several important risk
      factors have been found to impact the risk of developing PTSD including gender,
      age, education, IQ, race and ethnicity, sexual orientation, pre-trauma
      psychopathology, prior trauma exposure, familial psychiatric history, and
      neurobiological factors. This article outlines the state of research findings on
      pretraumatic, peritraumatic, and posttraumatic risk factors for the development
      of PTSD and associated psychopathology following trauma. 

PMID- 26206109
TI  - Current State of Radial Artery Catheterization in ST-Elevation Myocardial
      Infarction.
AB  - A well-established body of evidence demonstrating the advantages of a transradial
      approach for coronary angiography and intervention has led to worldwide adoption
      of this technique. In some countries, radial access has replaced femoral access
      as the dominant access site for percutaneous coronary intervention (PCI). More
      recently, numerous randomized controlled trials have compared transradial and
      transfemoral access in patients with ST elevation myocardial infarction (STEMI)
      and have shown that transradial access is associated with lower mortality and
      less major bleeding. This review examines the advantages of transradial primary
      PCI for STEMI patients, addresses concerns in adopting this approach for primary
      PCI, and reviews recommendations on how to start a transradial primary PCI
      program. 

PMID- 26206110
TI  - Culprit-Only vs. Complete Revascularization During ST-Segment Elevation
      Myocardial Infarction.
AB  - Primary percutaneous intervention (PCI) is the treatment of choice for ST-segment
      elevation myocardial infarction (STEMI). Patients with STEMI frequently have
      obstructive non-culprit lesions. In addition, STEMI patients with multivessel
      disease are at increased risk of major adverse cardiac events. However, current
      guidelines do not recommend revascularization of non-culprit lesions unless
      complicated by cardiogenic shock. Prior observational and small randomized
      controlled trials (RCTs) have demonstrated conflicting results pertaining to the
      optimal revascularization strategy in STEMI patients with multivessel disease
      undergoing primary PCI. Recent randomized studies, PRAMI, CvLPRIT, and DANAMI-3
      PRIMULTI, provide encouraging data that suggest potential benefit with complete
      revascularization in STEMI patients with obstructive non-culprit lesions.
      However, further data from large RCTs are needed to investigate the impact of
      this strategy on recurrent myocardial infarction/death and to determine the best
      timing of staged procedures for complete revascularization. Until then, a
      personalized approach should be taken to optimize the revascularization strategy
      in STEMI patients with obstructive non-culprit lesions. 

PMID- 26206112
TI  - Verbal Versus Figural Fluency Tests in Currently Ill and Weight Restored Anorexia
      Nervosa Patients.
AB  - Fluency tests allow domain-specific assessment of verbal and non-verbal executive
      functions (EF) comparison and also enable utilizing of both quantitative and
      qualitative scoring methods. Thirty-five currently ill anorexia nervosa patients
      (PANs), 33 weight-restored patients (WRAN) and 47 healthy controls (HCs) were
      administered the word fluency test and the five-point test. Results show that
      WRANs tended to perseverate more than HCs in the verbal-fluency test. In
      addition, PANs produced significantly less correct figures and perseverated more
      than HCs and WRANs; HCs used more strategy methods than PANs and WRANs.
      Additionally, a positive correlation was found in the HC group between the total
      number of words in the verbal phonemic test and the number of designs produced
      and the number of correct designs. No such correlations were found in both
      anorexia groups. In conclusion, there is a differentiation between verbal and non
      verbal EF in PANs and WRANs, showing a deficiency in the non-verbal domain. These
      findings may contribute to our understanding of the cognitive nature of the
      disorder.

PMID- 26206113
TI  - Family physicians enhance end-of-life care: evaluation of a new continuing
      medical education learning module in British Columbia.
AB  - BACKGROUND: The Practice Support Program (PSP) is an innovative peer-to-peer
      continuing medical education (CME) program that offers full-service family
      physicians/general practitioners (GPs) in British Columbia (BC), Canada, post
      graduate training on a variety of topics. We present the evaluation findings from
      the PSP learning module on enhancing end-of-life (EOL) care within primary care.
      METHODS: Pen-and-paper surveys were administered to participants three times: at
      the beginning of the first training session (n = 608; 69.6 % response rate), at
      training completion (n = 381, 55.6 % response rate), and via a mail-out survey at
      3-6 months following training completion (n = 109, 24.8 % response rate). Surveys
      asked GPs about current EOL-related practices and confidence in EOL-related
      skills. At end of training, respondents also provided ratings of satisfaction and
      perceptions of the module's impact on their practice and their EOL patients.
      RESULTS: Satisfaction and impact were rated very highly by over 90 % of the GP
      respondents. Module participation increased the GPs' confidence on EOL-related
      communication and collaboration skills: e.g., initiating conversations about EOL
      care, developing an action plan for EOL care, communicating the patient's needs
      and wishes to other care providers, participating in collaborative care with home
      and community care nurses, and accessing and referring patients to EOL
      specialists in the community. Increased confidence was maintained at 3-6 months
      following completion of training. CONCLUSIONS: The EOL learning module offered by
      the PSP to family physicians in BC is a successful and impactful CME accredited
      training module for enhancing end-of-life care in primary care settings.

PMID- 26206111
TI  - Revascularization vs. Medical Therapy in Stable Ischemic Heart Disease.
AB  - The keynote COURAGE and BARI-2D trials changed the way the interventional
      community selects patients for revascularization. What we now consider
      appropriate, especially for percutaneous coronary intervention, has narrowed
      significantly in scope compared to previous practice a decade ago. Medical
      therapy has been shown to be both safe and effective as a primary treatment
      modality for patients with stable ischemic heart disease on the whole. However,
      it appears that patients with a heavy ischemic burden may benefit from
      revascularization, although investigation of this is ongoing. Evidence
      preliminarily supports this practice with coronary artery bypass grafting, and
      possibly in specific populations undergoing multivessel intervention with
      functional assessment of lesion severity during PCI. 

PMID- 26206114
TI  - Efficacy, safety, and outcomes in 17 pediatric cases treated with the free
      radical scavenger edaravone.
AB  - SUBJECTS: Edaravone is a free radical scavenger with brain protection properties
      and is recommended by "The Japanese Guidelines for the Management of Stroke 2009"
      for administration to adult patients, in whom it has been shown to improve
      neurological deficits after cerebral infarction. However, its dosage and effects
      have not yet been established in children. METHODS: Seventeen pediatric patients
      with cerebral ischemia were administered edaravone at a dose based on body weight
      from the standard dose given to adults. Functional outcomes were evaluated using
      mRS and PSOM (modified ranking scale and pediatric stroke outcome scale,
      respectively). RESULTS: Immediate post-treatment results were mostly positive,
      with no liver or renal complications. In some cases, neurological symptoms
      markedly improved after the administration of edaravone. CONCLUSIONS: The
      efficacy of edaravone has not yet been examined in pediatric patients. The
      results of the present study suggest that edaravone has potential in the
      treatment of children safely with promising results similar to those in adults.

PMID- 26206115
TI  - Ictal urinary urge: localization and lateralization value in a pediatric case.
AB  - BACKGROUND: Ictal urinary urge is a rare autonomic symptom usually lateralizing
      to the non-dominant hemisphere and localizing to the temporal lobe. CASE REPORT:
      A 12-year-old boy was referred with desire to void and contraction of the left
      arm. The history of the case revealed tickling and an unpleasant rising feeling
      in the stomach and sense of fear lasting for 1 year. He had been evaluated and
      treated several times with the diagnosis of gastroesophageal reflux and cystitis.
      His cranial MRI displayed an intra-axial mass formation on the right temporal
      lobe. Pathological findings were consistent with a low-grade glial mass.
      CONCLUSION: Ictal urinary urge has a considerable value both for localization and
      lateralization of seizures.

PMID- 26206116
TI  - Congenital (infantile) fibrosarcoma of the scalp: a case series and review of
      literature.
AB  - INTRODUCTION: Congenital infantile fibrosarcoma (CIFS) is a soft tissue sarcoma
      of infants mainly involving lower extremities usually presenting during the first
      year of life. A subset of cases occur in the head and neck, but scalp involvement
      is exceptionally rare. PATIENTS AND METHODS: We report clinicopathological
      features of three cases of CIFS involving the scalp diagnosed between 2011 and
      2012. RESULTS: The ages of the three patients at the time of diagnosis ranged
      from 12 to 90 days (mean 48 days). All were males and presented with scalp
      swelling at birth which grew rapidly in size. The tumor was located in the left
      temporal region in two cases and the right temporoparietal region in one case. On
      imaging, underlying bone involvement was noted in two cases. The mean size of the
      resected tumors was 8 cm. All cases exhibited a cellular tumor arranged in sheets
      of uniform oval to spindle cells, increased mitosis, and hemangiopericytoma-like
      vessels. All patients are alive after a mean follow-up of 39.6 months. Recurrence
      was seen in one case due to incomplete excision. No metastasis was seen in any of
      the cases. CONCLUSION: CIFS of the scalp is rare and carries a good prognosis.
      Underlying bone erosion is rare but was noted seen in two of our cases. A male
      predominance was seen in our cases.

PMID- 26206117
TI  - Positively Biased Self-Perceptions in Children with ADHD: Unique Predictor of
      Future Maladjustment.
AB  - This study assessed children's overestimations of self-competence (positively
      biased self-perceptions or positive bias [PB]) relative to parent/teacher ratings
      of children's competence in predicting children's adjustment in a new setting.
      Eighty-five children (13 boys and 11 girls with Attention-Deficit/Hyperactivity
      Disorder [ADHD]; 30 boys and 31 girls who were typically developing [TD]), ages
      6.8 to 9.8 years (M = 8.13; SD = 0.82), attended a 2-week summer day camp grouped
      into same-age, same-sex classrooms with previously unacquainted peers and
      counselors. Prior to camp, PB was assessed by creating standardized discrepancy
      scores between children's self-ratings relative to parent or teacher ratings of
      the children's social and behavioral competence. The relative ability of these
      discrepancy scores to predict peer preference and oppositionality at camp in
      relation to parent or teacher ratings alone was evaluated. For children with
      ADHD, both discrepancy scores and informant ratings of competence were uniquely
      predictive of peer preference and oppositionality assessed during camp. For TD
      children, only informant ratings of competence were predictive of outcomes at
      camp. These results suggest that PB may be a unique predictor of maladjustment
      within a novel environment for children with ADHD, but not TD children.

PMID- 26206118
TI  - Classroom Interactions, Dyadic Teacher-Child Relationships, and Self-Regulation
      in Socially Disadvantaged Young Children.
AB  - This study examined the quality of the classroom climate and dyadic teacher-child
      relationships as predictors of self-regulation in a sample of socially
      disadvantaged preschool children (N = 206; 52 % boys). Children's self-regulation
      was observed in preschool at the beginning and at the end of the school year. At
      the middle of the preschool year, classroom observations of interactions were
      conducted by trained observers and teachers rated the quality of dyadic teacher
      child relationships. Results from multilevel analyses revealed that teacher-child
      closeness predicted improvements in observed self-regulation skills. Children
      showed larger gains in self-regulation when they experienced closer teacher-child
      relationships. Moreover, a moderating effect between classroom instructional
      quality and observed self-regulation was found such that children with low
      initial self-regulation skills benefit the most from classrooms with higher
      classroom quality. Findings have implications for understanding the role of
      classroom social processes on the development of self-regulation. 

PMID- 26206119
TI  - Performance and responses to competition in two congeneric annual species: does
      seed heteromorphism matter?
AB  - Variations in seed characteristics observed in heteromorphic species may affect
      various stages of their life cycles, e.g. seed dormancy, germination
      characteristics or even adult plant performance. Highly specialised seed morphs -
      described as colonisers and maintainers - exhibit a trade-off between
      colonisation capacity and competitive traits. The performance of distinct seed
      morph progeny under competitive conditions, and especially in multi-species
      arrangements, had previously not been given much attention. In this study, we
      compared performance and response to competition among distinct seed morph
      progenies in two congeneric, co-occurring species: the invasive Bidens frondosa
      and the non-invasive Bidens tripartita. We hypothesised that maintainer seed
      morphs of both species would perform better under increased plant densities and
      within inter-morphic mixtures, while coloniser morphs would show stronger
      responses to increased densities and perform relatively poorly in inter-morphic
      mixtures. We conducted a growth trial and a greenhouse experiment, which revealed
      that seed morph progeny differed significantly in plant height when grown without
      competition, while under competitive conditions such differences became less
      apparent. The observed pattern was more strongly pronounced in B. frondosa, which
      showed a general predominance in stature and biomass over its non-invasive
      congener. Although seed morphs performed equally well under competitive
      conditions, increased plant height and more rapid germination can favour the
      maintainer seed morph on sites where vegetation is already present. 

PMID- 26206120
TI  - omega-3 Polyunsaturated Fatty Acids Effects on the Cardiometabolic Syndrome and
      their Role in Cardiovascular Disease Prevention: An Update from the Recent
      Literature.
AB  - Docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid of the omega-3 family of
      polyunsaturated fatty acids (PUFA) are abundant in fatty fish and other marine
      sources. Their consistent consumption has been related to an improved
      cardiovascular risk especially in high risk patients and populations. In this
      review, we presented major findings about potential mechanisms of action and
      clinical evidence regarding omega-3 PUFA effect on the control and prevention of
      cardiovascular disease. This review is an update of our previous review (Colussi
      et al. Recent Pat Cardiovasc Drug Discov 2007;2:13-31) in which we additionally
      summarize and comment new literature of the past few years. Despite clinical
      studies have been significantly increased in the last years, the evidence in
      support of a beneficial role of omega-3 PUFA in cardiovascular prevention is
      still relatively weak. The growing improvement of medical interventions for
      cardiovascular prevention might explain why these molecules appear to have
      limited impact on the cardiovascular risk. 

PMID- 26206122
TI  - Reply.

PMID- 26206121
TI  - Genetic (KIR, HLA-C) and Some Clinical Parameters Influencing the Level of Liver
      Enzymes and Early Virologic Response in Patients with Chronic Hepatitis C.
AB  - Natural killer cells play an important role as effectors of innate immunity and
      regulators of adaptive immunity. They are important elements of the innate
      response to viral infections, which they detect using human leukocyte antigen
      (HLA) class I-binding receptors. Most polymorphic of these are killer cell
      immunoglobulin-like receptors (KIRs) which exist as two basic isotypes,
      activating or inhibitory receptors and are encoded by genes distributed
      differently in unrelated individuals. We searched for links between selected
      clinical data (including HCV viremia, liver enzymes level and liver histology
      parameters) and the presence of genes encoding these receptors and their ligands
      in hepatitis C virus-infected individuals subjected to pegylated interferon-alpha
      and ribavirin therapy. Genomic DNA samples from two hundred and ninety-two
      chronically infected patients were typed by polymerase chain reaction for the
      presence or absence of genes for KIRs and their ligands, class I HLA molecules,
      and clinical data of the patients were collected. Our results suggest an
      importance of clinical parameters and the contribution of KIR and HLA genes to
      the course of hepatitis C virus infection and the response to therapy. The study
      revealed that levels of liver enzymes before therapy were about 30% higher in
      patients who possessed a variant KIR2DS4 gene with 22-base pair deletion.
      Decrease of ALT activity after treatment was higher in HLA-C C2-positive than
      negative individuals. Beside it, patients demonstrated early virologic response
      to the therapy if the time lag before treatment was short, particularly in women.

PMID- 26206123
TI  - Phytoplankton dynamics with a special emphasis on harmful algal blooms in the Mar
      Piccolo of Taranto (Ionian Sea, Italy).
AB  - The response of phytoplankton assemblages to the closure of urban sewage outfalls
      (USOs) was examined for the Mar Piccolo of Taranto (Mediterranean Sea), a
      productive semi-enclosed coastal marine ecosystem devoted to shellfish farming.
      Phytoplankton dynamics were investigated in relation to environmental variables,
      with a particular emphasis on harmful algal blooms (HABs). Recent analyses
      evidenced a general reduction of the inorganic nutrient loads, except for
      nitrates and silicates. Also phytoplankton biomass (chlorophyll a) and abundances
      were characterized by a decrease of the values, except for the inner area of the
      basin (second inlet). The phytoplankton composition changed, with nano-sized
      species, indicators of oligotrophic conditions, becoming dominant over micro
      sized species. If the closure of the USOs affected phytoplankton dynamics,
      however, it did not preserve the Mar Piccolo from HABs and anoxia crises. About
      25 harmful species have been detected throughout the years, such as the
      potentially domoic acid producers Pseudo-nitzschia cf. galaxiae and P seudo
      nitzschia cf. multistriata, identified for the first time in these waters. The
      presence of HABs represents a threat for human health and aquaculture. Urgent
      initiatives are needed to improve the communication with authorities responsible
      for environmental protection, economic development, and public health for a
      sustainable mussel culture in the Mar Piccolo. 

PMID- 26206124
TI  - Effective conversion of maize straw wastes into bio-hydrogen by two-stage process
      integrating H2 fermentation and MECs.
AB  - The enhanced H2 production from maize straw had been achieved through the two
      stage process of integrating H2 fermentation and microbial electrolysis cells
      (MECs) in the present work. Several key parameters affecting hydrolysis of maize
      straw through subcritical H2O were optimized by orthogonal design for
      saccharification of maize straw followed by H2 production through H2
      fermentation. The maximum reducing sugar (RS) content of maize straw reached
      469.7 mg/g-TS under the optimal hydrolysis condition with subcritical H2O
      combining with dilute HCl of 0.3% at 230  degrees C. The maximum H2 yield, H2
      production rate, and H2 content was 115.1 mL/g-TVS, 2.6 mL/g-TVS/h, and 48.9% by
      H2 fermentation, respectively. In addition, the effluent from H2 fermentation was
      used as feedstock of MECs for additional H2 production. The maximum H2 yield of
      1060 mL/g-COD appeared at an applied voltage of 0.8 V, and total COD removal
      reached about 35%. The overall H2 yield from maize straw reached 318.5 mL/g-TVS
      through two-stage processes. The structural characterization of maize straw was
      also carefully investigated by scanning electron microscopy (SEM), Fourier
      transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) spectra.

PMID- 26206125
TI  - Efficient photocatalytic degradation of organic pollutants by magnetically
      recoverable nitrogen-doped TiO2 nanocomposite photocatalysts under visible light
      irradiation.
AB  - Preparation of novel nanocomposite particles (NCPs) with high visible-light
      driven photocatalytic activity and possessing recovery potential after advanced
      oxidation process (AOP) is much desired. In this study, pure anatase phase
      titania (TiO2) nanoparticles (NPs) as well as three types of NCPs including
      nitrogen-doped titania (TiO2-N), titania-coated magnetic silica (Fe3O4
      cluster@SiO2@TiO2 (FST)), and a novel magnetically recoverable TiO2 nanocomposite
      photocatalyst containing nitrogen element (Fe3O4 cluster@SiO2@TiO2-N (FST-N))
      were successfully synthesized via a sol-gel process. The photocatalysts were
      characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR)
      spectroscopy, field emission scanning electron microscopy (FE-SEM) with an energy
      dispersive X-ray (EDX) spectroscopy analysis, X-ray photoelectron spectroscopy
      (XPS), UV-vis diffuse reflectance spectroscopy (DRS), and vibrating sample
      magnetometer (VSM). The photocatalytic activity of as-prepared samples was
      further investigated and compared with each other by degradation of phenol, as a
      model for the organic pollutants, in deionized (DI) water under visible light
      irradiation. The TiO2-N (55 +/- 1.5%) and FST-N (46 +/- 1.5%) samples exhibited
      efficient photocatalytic activity in terms of phenol degradation under visible
      light irradiation, while undoped samples were almost inactive under same
      operating conditions. Moreover, the effects of key operational parameters, the
      optimum sample calcination temperature, and reusability of FST-N NCPs were
      evaluated. Under optimum conditions (calcination temperature of 400  degrees C
      and near-neutral reaction medium), the obtained results revealed efficient
      degradation of phenol for FST-N NCPs under visible light irradiation (46 +/-
      1.5%), high yield magnetic separation and efficient reusability of FST-N NCPs
      (88.88% of its initial value) over 10 times reuse.

PMID- 26206127
TI  - Erratum to: Characterization of water reservoirs affected by acid mine drainage:
      geochemical, mineralogical, and biological (diatoms) properties of the water.

PMID- 26206126
TI  - Induction of reactive oxygen species in marine phytoplankton under crude oil
      exposure.
AB  - Exposure of phytoplankton to the water-accommodated fraction of crude oil can
      elicit a number of stress responses, but the mechanisms that drive these
      responses are unclear. South Louisiana crude oil was selected to investigate its
      effects on population growth, chlorophyll a (Chl a) content, antioxidative
      defense, and lipid peroxidation, for the marine diatom, Ditylum brightwellii, and
      the dinoflagellate, Heterocapsa triquetra, in laboratory-based microcosm
      experiments. The transcript levels of several possible stress-responsive genes in
      D. brightwellii were also measured. The microalgae were exposed to crude oil for
      up to 96 h, and Chl a content, superoxide dismutase (SOD), the glutathione pool
      (GSH and GSSG), and lipid peroxidation content were analyzed. The cell growth of
      both phytoplankton species was inhibited with increasing crude oil
      concentrations. Crude oil exposure did not affect Chl a content significantly in
      cells. SOD activities showed similar responses in both species, being enhanced at
      4- and 8-mg/L crude oil exposure. Only H. triquetra demonstrated enhanced
      activity in GSSG pool and lipid peroxidation at 8-mg/L crude oil exposure,
      suggesting that phytoplankton species have distinct physiological responses and
      tolerance levels to crude oil exposure. This study indicated the activation of
      reactive oxygen species (ROS) in phytoplankton under crude oil exposure; however,
      the progressive damage in cells is still unknown. Thus, ROS-related damage in
      nucleic acid, lipids, proteins, and DNA, due to crude oil exposure could be a
      worthwhile subject of study to better understand crude oil toxicity at the base
      of the food web.

PMID- 26206128
TI  - Gene-modified embryonic stem cell test to characterize chemical risks.
AB  - A high-throughput test of cell growth inhibition was performed using mouse
      embryonic stem (ES) cells to assess chemical toxicities. We herein demonstrated
      using a 96-well culture plate approach and the MTT assay that this method was
      suitable for prioritization of chemicals for their cytotoxic properties. In order
      to categorize chemicals, we used p53 gene-modified mouse ES cells as well as wild
      type ES cells. The p53 gene is a well-known tumor suppressor and controls
      programmed cell death (apoptosis) and cellular senescence that is triggered by
      DNA-damaging agents such as alkylating agents and radiation. In the present
      study, p53-deficient ES cells were found to be more resistant to a tumor
      initiator, diethylnitrosamine (DEN), than wild-type ES cells, suggesting the
      inhibition of apoptosis or senescence by a dysfunction in p53. Chromosome
      aberrations were more frequently detected in p53-deficient ES cells than in wild
      type cells, indicating genomic instability due to the deletion of p53. Other
      tumor initiators, methyl methanesulfonate (MMS) and N-methyl-N-nitrosourea (NMU),
      did not reveal apparent differences in cytotoxicity between wild-type and p53
      deficient ES cells. Thus, ES test system using gene-modified ES cells may be used
      to categorize chemicals by detecting their characteristic effects on apoptosis,
      genotoxic potentials as well as general cytotoxicity. 

PMID- 26206129
TI  - Analysis of predictors related to soil contamination in recreational areas of
      Romania.
AB  - Soil contamination in recreational areas can considerably affect children's
      health, as they are the segment of the population most sensitive to anthropogenic
      contamination. Soil contamination in recreational areas is influenced by a number
      of factors such as type and age of the recreational area, nearby traffic
      intensity, proximity to industrial areas, presence of vegetation, level of usage,
      treated wood structures, and the extent of maintenance operations carried out in
      the area. These can most often be observed during a simple site visit. The
      purpose of the present research is to analyze to which extent the presence of
      these factors can trigger an alarm signal, highlighting soil contamination in
      urban recreational areas. In this regard, soil contamination was scaled using the
      integrated pollution index applied on nine distinctive contaminants (As, Cu, Cd,
      Zn, Pb, Hg, Co, Ni, Mg) identified using inductively coupled plasma mass
      spectrometry (ICP-MS). Multiple linear regression analysis was performed in order
      to assess predictors of soil contamination. The research was carried out in a
      number of 88 recreational areas, parks, and playgrounds from 19 Romanian cities,
      revealing the fact that proximity to industrial areas and intensive traffic had
      statistically significant effects on soil contamination. Furthermore, it was
      observed that in 78 out of the 88 analyzed locations, the concentrations of
      contaminants exceeded the guidelines established through national legislation,
      thus confirming the presumption that high concentrations of contaminants exist in
      the parks and playgrounds of Romania. 

PMID- 26206130
TI  - Characterization of H2S removal and microbial community in landfill cover soils.
AB  - H2S is a source of odors at landfills and poses a threat to the surrounding
      environment and public health. In this work, compared with a usual landfill cover
      soil (LCS), H2S removal and biotransformation were characterized in waste
      biocover soil (WBS), an alternative landfill cover material. With the input of
      landfill gas (LFG), the gas concentrations of CH4, CO2, O2, and H2S, microbial
      community and activity in landfill covers changed with time. Compared with LCS,
      lower CH4 and H2S concentrations were detected in the WBS. The potential sulfur
      oxidizing rate and sulfate-reducing rate as well as the contents of acid-volatile
      sulfide, SO4(2-), and total sulfur in the WBS and LCS were all increased with the
      input of LFG. After exposure to LFG for 35 days, the sulfur-oxidizing rate of the
      bottom layer of the WBS reached 82.5 MUmol g dry weight (d.w.)(-1) day(-1), which
      was 4.3-5.4 times of that of LCS. H2S-S was mainly deposited in the soil covers,
      while it escaped from landfills to the atmosphere. The adsorption, absorption,
      and biotransformation of H2S could lead to the decrease in the pH values of
      landfill covers; especially, in the LCS with low pH buffer capacity, the pH value
      of the bottom layer dropped to below 4. Pyrosequencing of 16S ribosomal RNA
      (rRNA) gene showed that the known sulfur-metabolizing bacteria Ochrobactrum,
      Paracoccus, Comamonas, Pseudomonas, and Acinetobacter dominated in the WBS and
      LCS. Among them, Comamonas and Acinetobacter might play an important role in the
      metabolism of H2S in the WBS. These findings are helpful to understand sulfur
      bioconversion process in landfill covers and to develop techniques for
      controlling odor pollution at landfills.

PMID- 26206131
TI  - Metal uptake of tomato and alfalfa plants as affected by water source, salinity,
      and Cd and Zn levels under greenhouse conditions.
AB  - Irrigation with wastewater is a promising option to improve crop yields and to
      reduce pressure on freshwater sources. However, heavy metal concentrations in
      wastewater may cause health concerns. A greenhouse pot experiment was conducted
      in order to determine cadmium (Cd) and zinc (Zn) concentrations in sandy soil and
      plant tissues of tomato (Lycopersicon esculentum L.) and alfalfa (Medicago sativa
      L.). A 2 * 2 * 4 * 2 factorial treatment arrangement was utilized. Two water
      sources, fresh (FW) or treated wastewater (TWW), at two salinity levels (1 and 3
      dS m(-1)) containing different levels of Cd and Zn were used. Samples were
      collected after a 90-day growth period. It was observed that the growth of both
      plants was depressed at the highest metal level (L3). Metal accumulation in plant
      parts increased with the increase of metal concentration and salinity in
      irrigation water. At low salinity, water source was the main factor which
      controlled metal accumulation, whereas, at high salinity, chloride appeared to be
      the principal factor controlling metal uptake regardless of water source. Metal
      translocation from roots to shoots increased in TWW-irrigated plants, even in the
      controls. Tomatoes accumulated Cd up to and above critical levels safe for human
      consumption, even though Cd concentration in irrigation water did not exceed the
      current recommended values. Therefore, food production in sandy soils may well
      pose a health hazard when irrigated with TWW containing heavy metals.
      Complexation with dissolved organic compounds (DOC) in TWW may be to be the
      principal factor responsible for increased metal uptake and transfer at low
      salinity, thereby increasing the risk of heavy metal contamination of food and
      forage crops.

PMID- 26206132
TI  - Biosorption studies on copper (II) and cadmium (II) using pretreated rice straw
      and rice husk.
AB  - This study investigated the adsorption and removal behaviour of copper (Cu) (II)
      and cadmium (Cd) (II) ions using rice husk and rice straw in aqueous solutions.
      Different parameters were used to investigate their adsorption performance in
      saline conditions and the optimal level of biosorption at different pH levels.
      The main parameters were pH (3, 6 and 9), initial concentration level of heavy
      metals (Cu (II) 5, 10, 20, 40 and 60 mg/L and Cd (II) 0.5, 1, 2, 4 and 8 mg/L,
      respectively), salinity (0, 50 and 100 mM NaCl) and contact time (ranging from 3
      to 60 min). Langmuir and Freundlich isotherm models were applied to analyse the
      removal efficiency and sorption capacity of the pretreated rice husk and rice
      straw. The removal efficiency and adsorption capacity generally increased with
      the pH and reached a plateau in alkaline conditions. The percentage removal of Cu
      (II) by rice husk reached 97 % at pH 9 and 95 % by rice straw at pH 6.
      Biosorption performance increased in the absence of NaCl. Kinetic studies for
      both metals revealed that the biosorption of Cu (II) and Cd (II) onto rice straw
      and husk was pseudo-second order.

PMID- 26206133
TI  - Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate
      self-renewal of trophoblast stem cells.
AB  - Esrrb (oestrogen-related receptor beta) is a transcription factor implicated in
      embryonic stem (ES) cell self-renewal, yet its knockout causes intrauterine
      lethality due to defects in trophoblast development. Here we show that in
      trophoblast stem (TS) cells, Esrrb is a downstream target of fibroblast growth
      factor (Fgf) signalling and is critical to drive TS cell self-renewal. In
      contrast to its occupancy of pluripotency-associated loci in ES cells, Esrrb
      sustains the stemness of TS cells by direct binding and regulation of TS cell
      specific transcription factors including Elf5 and Eomes. To elucidate the
      mechanisms whereby Esrrb controls the expression of its targets, we characterized
      its TS cell-specific interactome using mass spectrometry. Unlike in ES cells,
      Esrrb interacts in TS cells with the histone demethylase Lsd1 and with the RNA
      Polymerase II-associated Integrator complex. Our findings provide new insights
      into both the general and context-dependent wiring of transcription factor
      networks in stem cells by master transcription factors. 

PMID- 26206134
TI  - Reliability and Validity of the Psoriasis Symptom Inventory in Patients With
      Psoriatic Arthritis.
AB  - OBJECTIVE: To evaluate the measurement properties of the Psoriasis Symptom
      Inventory (PSI) in psoriatic arthritis (PsA). METHODS: The PSI is an 8-item,
      patient-reported outcome measure of the severity of psoriasis signs and symptoms.
      This was a secondary analysis of pooled data from a phase II study evaluating the
      efficacy of brodalumab in patients with PsA. Unidimensionality and item
      evaluation were assessed using factor and Rasch analyses. Reliability was
      assessed using Cronbach's alpha (internal consistency) and intraclass correlation
      coefficients (ICCs) for PSI scores in patients with stable disease (test-retest).
      Construct validity was evaluated by correlations between PSI scores and body
      surface area (BSA) affected by psoriasis and selected Short Form 36 (SF-36)
      health survey domains. Known-groups validity was evaluated based on BSA severity
      categories, and the ability to detect change was evaluated based on improvement
      in the subject's global assessment (SGA). RESULTS: The analysis sample (n = 154)
      was 93.5% white and 63.0% female. The mean +/- SD baseline affected BSA was 10.4%
      +/- 15.6%, and age was 52.2 +/- 11.5 years. The PSI demonstrated
      unidimensionality, with good item fit and correctly ordered categories, excellent
      internal consistency (alpha = 0.95), good test-retest reliability (total score
      ICC 0.70; item ICCs range 0.67-0.81), convergent validity based on moderate
      correlations with BSA (r = 0.50), discriminant validity based on small baseline
      correlations (r <-0.3) with the SF-36 domains (role-physical, role-emotional,
      vitality), known groups validity based on significant differences between BSA
      groups, and responsiveness based on SGA improvements (P < 0.05). CONCLUSION: The
      PSI demonstrated excellent test-retest and internal consistency reliability and
      good construct validity in measuring psoriasis signs and symptoms severity in
      PsA.

PMID- 26206135
TI  - L-Asparaginase from Streptomyces griseus NIOT-VKMA29: optimization of process
      variables using factorial designs and molecular characterization of L
      asparaginase gene.
AB  - Marine actinobacteria are known to be a rich source for novel metabolites with
      diverse biological activities. In this study, a potential extracellular L
      asparaginase was characterised from the Streptomyces griseus NIOT-VKMA29. Box
      Behnken based optimization was used to determine the culture medium components to
      enhance the L-asparaginase production. pH, starch, yeast extract and L-asparagine
      has a direct correlation for enzyme production with a maximum yield of 56.78 IU
      mL(-1). A verification experiment was performed to validate the experiment and
      more than 99% validity was established. L-Asparaginase biosynthesis gene (ansA)
      from Streptomyces griseus NIOT-VKMA29 was heterologously expressed in Escherichia
      coli M15 and the enzyme production was increased threefold (123 IU mL(-1)) over
      the native strain. The ansA gene sequences reported in this study encloses
      several base substitutions with that of reported sequences in GenBank, resulting
      in altered amino acid sequences of the translated protein. 

PMID- 26206136
TI  - Heptaphosphide cluster anions bearing group 14 element amide functionalities.
AB  - Reactions of the protonated heptaphosphide dianion, [HP7](2-), with one
      equivalent of E[N(SiMe3)2]2 (E = Ge, Sn, Pb) give rise to novel derivatized
      cluster anions [P7EN(SiMe3)2](2-) (E = Ge (1), Sn (2) and Pb (3)). All three
      species were characterized by multi-element solution-phase NMR spectroscopy and
      electrospray ionization mass spectrometry. In addition, 1 and 2 were structurally
      authenticated by means of single crystal X-ray diffraction in [K(18-crown
      6)]2[P7EN(SiMe3)2].2py. Interestingly, while 2 appears to be indefinitely stable
      in solution for prolonged periods of time, the germanium-containing analogue, 1,
      readily decomposes at room temperature giving rise to the dimeric species
      [(P7Ge)2N(SiMe3)2](3-) (4) and [K(18-crown-6)][N(SiMe3)2]. A low quality single
      crystal X-ray structure of the former allowed for the confirmation of its
      composition and connectivity which is consistent with the (31)P NMR spectrum
      obtained for the anion. 

PMID- 26206137
TI  - Characteristics and analysis of scientific articles submitted to the European
      Annals of Otorhinolaryngology, Head and Neck Diseases.
AB  - OBJECTIVES: To evaluate characteristics, suggested modifications and reasons for
      rejection in scientific articles submitted for publication in the European Annals
      of Otorhinolaryngology, Head and Neck Diseases. MATERIALS AND METHODS: A
      prospective study analyzed the flaws noted by reviewers in 52 scientific articles
      submitted to the European Annals of Otorhinolaryngology, Head and Neck Diseases
      between August 31, 2014 and February 28, 2015. RESULTS: Fifteen flaws concerning
      content and 7 concerning form were identified. In more than 25% of submissions,
      major flaws were noted: purely descriptive paper; lack of contribution to
      existing state of knowledge; failure to define a clear study objective and/or
      analyze the impact of major variables; poorly structured Materials and methods
      section, lacking description of study population, objective and/or variables;
      lack of or inappropriate statistical analysis; Introduction verbose and/or
      misrepresenting the literature; excessively heterogeneous and/or poorly described
      study population; imprecise discussion, straying from the point, overstating the
      significance of results and/or introducing new results not mentioned in the
      Results section; description of the study population placed in the Results
      section instead of under Materials and methods; serious mistakes of syntax,
      spelling and/or tense; and failure to follow the Instructions to Authors. After
      review, 21.1% of articles were published, 65.3% rejected and 13.4% non
      resubmitted within 3 months of review. On univariate analysis, the only variable
      increasing the percentage of articles accepted was the topic not being devoted to
      head and neck surgery (P=0.03). CONCLUSION: These results document the excessive
      flaw rate still to be found in manuscripts and demonstrate the continuing need
      for authors to master and implement the rules of scientific medical writing.

PMID- 26206138
TI  - Induction of innate immunity and its perturbation by influenza viruses.
AB  - Influenza A viruses (IAV) are highly contagious pathogens causing dreadful losses
      to human and animal, around the globe. IAVs first interact with the host through
      epithelial cells, and the viral RNA containing a 5'-triphosphate group is thought
      to be the critical trigger for activation of effective innate immunity via
      pattern recognition receptors-dependent signaling pathways. These induced immune
      responses establish the antiviral state of the host for effective suppression of
      viral replication and enhancing viral clearance. However, IAVs have evolved a
      variety of mechanisms by which they can invade host cells, circumvent the host
      immune responses, and use the machineries of host cells to synthesize and
      transport their own components, which help them to establish a successful
      infection and replication. In this review, we will highlight the molecular
      mechanisms of how IAV infection stimulates the host innate immune system and
      strategies by which IAV evades host responses.

PMID- 26206141
TI  - Successful multimodality treatment of recalcitrant necrobiotic xanthogranuloma
      using electron beam radiation and intravenous immunoglobulin.
AB  - Necrobiotic xanthogranuloma (NXG) is a rare dermatosis with a poorly understood
      pathophysiology. Studies comparing treatments for such lesions are limited. We
      present the case of a patient with a 30-year history of NXG refractory to several
      individual therapeutic interventions [excision, intravenous immunoglobulin
      (IVIg), systemic chemotherapies and immunosuppressants, cryotherapy and laser
      therapy], who ultimately responded to a combination of treatment with electron
      beam radiation therapy (EBRT) in conjunction with IVIg. This combined treatment
      resulted in flattening of the NXG lesions and a reduction of symptomatic pruritus
      within the treatment zone. EBRT may represent a potent treatment for NXG, and
      formal trials evaluating its effectiveness may yield insights into the management
      of NXG.

PMID- 26206140
TI  - Oxygen sensing in intestinal mucosal inflammation.
AB  - Hypoxia is a hallmark of chronically inflamed tissue. Hypoxia develops from
      vascular dysfunction and increased oxygen consumption by infiltrating leukocytes.
      With respect to inflammatory bowel disease (IBD), hypoxia is likely to be of
      particular importance: Impairment of the intestinal barrier during IBD allows
      anoxia from the lumen of the gut to spread to formerly normoxic tissue. In
      addition, disturbed perfusion of inflamed tissue and a higher oxygen demand of
      infiltrating immune cells lead to low oxygen levels in inflamed mucosal tissue.
      Here, cells become hypoxic and must now adapt to this condition. The hypoxia
      inducible factor (HIF)-1 complex is a key transcription factor for cellular
      adaption to low oxygen tension. HIF-1 is a heterodimer formed by two subunits:
      HIF-alpha (either HIF-1alpha or HIF-2alpha) and HIF-1beta. Under normoxic
      conditions, hydroxylation of the HIF-alpha subunit by specific oxygen-dependent
      prolyl hydroxylases (PHDs) leads to ubiquitin proteasome-dependent degradation.
      Under hypoxic conditions, however, PHD activity is inhibited; thus, HIF-alpha can
      translocate into the nucleus, dimerize with HIF-1beta, and bind to hypoxia
      responsive elements of HIF-1 target genes. So far, most studies have addressed
      the function of HIF-1alpha in intestinal epithelial cells and the effect of HIF
      stabilization by PHD inhibitors in murine models of colitis. Furthermore, the
      role of HIF-1alpha in immune cells becomes more and more important as T cells or
      dendritic cells for which HIF-1 is of critical importance are highly involved in
      the pathogenesis of IBD. This review will summarize the function of HIF-1alpha
      and the therapeutic prospects for targeting the HIF pathway in intestinal mucosal
      inflammation. 

PMID- 26206139
TI  - Characterizing functional connectivity patterns during saliva swallows in
      different head positions.
AB  - BACKGROUND: The anatomical rationale and efficacy of the chin tuck in improving
      airway protection for some people with swallowing disorders have been well
      researched and established. However, there are still open questions regarding
      whether brain activity for swallowing control is altered while performing this
      chin-tuck maneuver. METHODS: In this study, we collected EEG signals from 55
      healthy adults while swallowing in the neutral and chin-tuck head positions. The
      time-frequency based synchrony measure was used to form brain networks. We
      investigated both the small-world properties of these brain networks and
      differences among the constructed brain networks for the two head positions
      during swallowing tasks. RESULTS: We showed that brain networks for swallowing in
      both head positions exhibit small-world properties. Furthermore, we showed that
      swallowing in the chin-tuck head position affects brain networks in the Alpha and
      Gamma frequency bands. CONCLUSIONS: According to these results, we can tell that
      the parameter of head position should be considered in future investigations
      which utilize EEG signals during swallowing activity.

PMID- 26206142
TI  - The Efficacy of Platelet-Rich Plasma Injection in the Management of Hip
      Osteoarthritis: A Systematic Review Protocol.

PMID- 26206143
TI  - Absence of correlation between ex vivo susceptibility to doxycycline and pfteQ
      pfmdt gene polymorphism in French Guiana.
AB  - BACKGROUND: In French Guiana, doxycycline is used for both chemoprophylaxis and
      the treatment of malaria. The presence of isolates with reduced ex vivo
      susceptibility to doxycycline in French Guiana makes it critical to identify any
      genetic determinants contributing to the chemosusceptibility level of Plasmodium
      falciparum to doxycycline, such as pfmdt and pftetQ, which were recently
      identified as potential molecular markers in African isolates. METHODS: A
      Bayesian statistical approach was used to define different ex vivo doxycycline
      phenotypes. The pfmdt and pftetQ gene copy numbers were quantified by
      quantitative real-time polymerase chain reaction in 129 P. falciparum isolates
      collected between 2000 and 2010, and pftetQ, pfrps7, pfssurRNA, and pflsurRNA
      sequences were analysed after amplification by polymerase chain reaction.
      RESULTS: PftetQ and pfmdt copy numbers were not associated with reduced
      susceptibility to doxycycline in P. falciparum within French Guiana. Sequence
      analysis of the genes revealed five known single nucleotide polymorphisms. Three
      new SNPs were identified in the apicoplast ribosomal RNA long sub-unit
      (pflsurRNA): C740T, A1875C and A1875T. These polymorphisms were not associated
      with reduced chemosusceptibility to doxycycline. CONCLUSIONS: The present study
      does not validate pfmdt and pftetQ genes as molecular markers of decreased
      susceptibility to doxycycline in P. falciparum isolates in French Guiana.

PMID- 26206144
TI  - Effect of mammographic screening from age 40 years on breast cancer mortality in
      the UK Age trial at 17 years' follow-up: a randomised controlled trial.
AB  - BACKGROUND: Age-specific effects of mammographic screening, and the timing of
      such effects, are a matter of debate. The results of the UK Age trial, which
      compared the effect of invitation to annual mammographic screening from age 40
      years with commencement of screening at age 50 years on breast cancer mortality,
      have been reported at 10 years of follow-up and showed no significant difference
      in mortality between the trial groups. Here, we report the results of the UK Age
      trial after 17 years of follow-up. METHODS: Women aged 39-41 from 23 UK NHS
      Breast Screening Programme units years were randomly assigned by individual
      randomisation (1:2) to either an intervention group offered annual screening by
      mammography up to and including the calendar year of their 48th birthday or to a
      control group receiving usual medical care (invited for screening at age 50 years
      and every 3 years thereafter). Both groups were stratified by general practice.
      We compared breast cancer incidence and mortality by time since randomisation.
      Analyses included all women randomly assigned who could be traced with the
      National Health Service Central Register and who had not died or emigrated before
      entry. The primary outcome measures were mortality from breast cancer (defined as
      deaths with breast cancer coded as the underlying cause of death) and breast
      cancer incidence, including in-situ, invasive, and total incidence. Because there
      is an interest in the timing of the mortality effect, we analysed the results in
      different follow-up periods. This trial is registered, number ISRCTN24647151.
      FINDINGS: Between Oct 14, 1990, and Sept 25, 1997, 160 921 participants were
      randomly assigned; 53 883 women in the intervention group and 106 953 assigned to
      usual medical care were included in this analysis. After a median follow-up of 17
      years (IQR 16.8-18.8), the rate ratio (RR) for breast cancer mortality was 0.88
      (95% CI 0.74-1.04) from tumours diagnosed during the intervention phase. A
      significant reduction in breast cancer mortality was noted in the intervention
      group compared with the control group in the first 10 years after diagnosis (RR
      0.75, 0.58-0.97) but not thereafter (RR 1.02, 0.80-1.30) from tumours diagnosed
      during the intervention phase. The overall breast cancer incidence during 17 year
      follow-up was similar between the intervention group and the control group (RR
      0.98, 0.93-1.04). INTERPRETATION: Our results support an early reduction in
      mortality from breast cancer with annual mammography screening in women aged 40
      49 years. Further data are needed to fully understand long-term effects.
      Cumulative incidence figures suggest at worst a small amount of overdiagnosis.
      FUNDING: National Institute for Health Research Health Technology Assessment
      programme and the American Cancer Society. Past funding was received from the
      Medical Research Council, Cancer Research UK, the UK Department of Health, and
      the US National Cancer Institute.

PMID- 26206145
TI  - The UK Age Trial: screening women in their forties.

PMID- 26206146
TI  - Adjuvant lymph-node field radiotherapy versus observation only in patients with
      melanoma at high risk of further lymph-node field relapse after lymphadenectomy
      (ANZMTG 01.02/TROG 02.01): 6-year follow-up of a phase 3, randomised controlled
      trial.
AB  - BACKGROUND: Adjuvant radiotherapy is recommended for patients with melanoma after
      lymphadenectomy. We previously showed this treatment reduced risk of repeat lymph
      node field cancer in patients with a high risk of recurrence but had no effect on
      overall survival. Here, we aim to update the relapse and survival data from that
      trial and assess quality of life and toxic effects. METHODS: In the ANZMTG
      01.02/TROG 02.01 randomised controlled trial, we enrolled patients who had
      undergone lymphadenectomy for a palpable lymph-node field relapse and were at
      high risk of recurrence at 16 hospitals (11 in Australia, three in New Zealand,
      one in Netherlands, and one in Brazil). We randomly assigned patients (1:1) to
      adjuvant radiotherapy (48 Gy in 20 fractions, given over a maximum of 30 days) or
      observation, stratified by institution, areas of lymph-node field (parotid and
      cervical, axilla, or groin), number of involved nodes (<=3 vs >3), maximum
      involved node diameter (<=4 cm vs >4 cm), and extent of extracapsular extension
      (none, limited, or extensive). Participants, those giving treatment, and those
      assessing outcomes were not masked to treatment allocation, but participants were
      unaware of each other's treatment allocation. In this follow-up, we assessed
      outcomes every 3 months from randomisation for the first 2 years, then every 6
      months up to 5 years, then annually. The primary endpoint was lymph-node field
      relapse as a first relapse, assessed in patients without major eligibility
      infringements (determined by an independent data monitoring committee). We
      assessed late adverse effects (occurring >90 days after surgery or start of
      radiotherapy) with standard criteria in the as-treated population. This study is
      registered with ClinicalTrials.gov, number NCT00287196. FINDINGS: Between March
      21, 2003, and Nov 15, 2007, we randomly assigned 123 patients to adjuvant
      radiotherapy (109 eligible for efficacy assessments) and 127 to observation (108
      eligible). The final follow-up date was Nov 15, 2011. Median follow-up was 73
      months (IQR 61-91). 23 (21%) relapses occurred in the adjuvant radiotherapy group
      compared with 39 (36%) in the observation group (adjusted hazard ratio [HR] 0.52
      [95% CI 0.31-0.88], p=0.023). Overall survival (HR 1.27 [95% CI 0.89-1.79],
      p=0.21) and relapse-free survival (0.89 [0.65-1.22], p=0.51) did not differ
      between groups. Minor, long-term toxic effects from radiotherapy (predominantly
      pain, and fibrosis of the skin or subcutaneous tissue) were common, and 20 (22%)
      of 90 patients receiving adjuvant radiotherapy developed grade 3-4 toxic effects.
      18 (20%) of 90 patients had grade 3 toxic effects, mainly affecting skin (nine
      [10%] patients) and subcutaneous tissue (six [7%] patients). Over 5 years, a
      significant increase in lower limb volumes was noted after adjuvant radiotherapy
      (mean volume ratio 15.0%) compared with observation (7.7%; difference 7.3% [95%
      CI 1.5-13.1], p=0.014). No significant differences in upper limb volume were
      noted between groups. INTERPRETATION: Long-term follow-up supports our previous
      findings. Adjuvant radiotherapy could be useful for patients for whom lymph-node
      field control is a major issue, but entry to an adjuvant systemic therapy trial
      might be a preferable first option. Alternatively, observation, reserving surgery
      and radiotherapy for a further recurrence, might be an acceptable strategy.
      FUNDING: National Health and Medical Research Council of Australia, Cancer
      Council Australia, Melanoma Institute Australia, and the Cancer Council South
      Australia.

PMID- 26206148
TI  - Human Cumulative Irritation Tests of Common Preservatives Used in Personal Care
      Products: A Retrospective Analysis of Over 45 000 Subjects.
AB  - The cumulative irritation test (CIT) is an accepted method used to evaluate the
      skin irritation potential and safety of individual ingredients and formulas of
      leave-on skin care and cosmetic compounds. Here, we report the results of CITs
      collected by JOHNSON & JOHNSON Consumer Companies, Inc. (Skillman, NJ), part of
      an extensive tiered program to evaluate product safety. In the CIT, test
      formulations were applied to the skin of adults (18-70 years) with no known skin
      disease or allergies, 3 times per week for 2 weeks using semi-occlusive clinical
      patches. Preservatives were 1 of up to 16 components of test formulas, and
      included ethylenediaminetetraacetic acid, diazolidinyl urea, 1,3
      Bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione, parabens,
      isothiazolinone, phenoxyethanol, sorbates, or benzoates. Skin sites were scored
      after each patch removal using a 5-point scale, with 0 = no visible reaction and
      4 = erythema, marked edema, or substantial vesiculation. Scores were reported as
      percentage of maximal irritation score. Data were analyzed from 1363 CIT studies
      (over 45 000 subjects). There were no significant differences in percentage of
      maximal scores between formulas grouped by preservative types (p > .1). Median
      score across the entire dataset was 0.44, with most formulas showing none or mild
      irritation. Although seasonal variations were observed, no correlation was noted
      between score and preservative concentration. In conclusion, in a large, normal
      subject dataset, preservatives at typical in-use concentrations did not appear to
      contribute to skin irritation.

PMID- 26206150
TI  - Setting Clinical Exposure Levels of Concern for Drug-Induced Liver Injury (DILI)
      Using Mechanistic in vitro Assays.
AB  - Severe drug-induced liver injury (DILI) remains a major safety issue due to its
      frequency of occurrence, idiosyncratic nature, poor prognosis, and diverse
      underlying mechanisms. Numerous experimental approaches have been published to
      improve human DILI prediction with modest success. A retrospective analysis of
      125 drugs (70 = most-DILI, 55 = no-DILI) from the Food and Drug Administration
      Liver Toxicity Knowledge Base was used to investigate DILI prediction based on
      consideration of human exposure alone or in combination with mechanistic assays
      of hepatotoxic liabilities (cytotoxicity, bile salt export pump inhibition, or
      mitochondrial inhibition/uncoupling). Using this dataset, human plasma Cmax,total
      >= 1.1 uM alone distinguished most-DILI from no-DILI compounds with high
      sensitivity/specificity (80/73%). Accounting for human exposure improved the
      sensitivity/specificity for each assay and helped to derive predictive safety
      margins. Compounds with plasma Cmax,total >= 1.1 uM and triple liabilities had
      significantly higher odds ratio for DILI than those with single/dual liabilities.
      Using this approach, a subset of recent pharmaceuticals with evidence of liver
      injury during clinical development was recognized as potential hepatotoxicants.
      In summary, plasma Cmax,total >= 1.1 uM along with multiple mechanistic
      liabilities is a major driver for predictions of human DILI potential. In
      applying this approach during drug development the challenge will be generating
      accurate estimates of plasma Cmax,total at efficacious doses in advance of
      generating true exposure data from clinical studies. In the meantime, drug
      candidates with multiple hepatotoxic liabilities should be deprioritized, since
      they have the highest likelihood of causing DILI in case their efficacious plasma
      Cmax,total in humans is higher than anticipated.

PMID- 26206149
TI  - Potential Adverse Effects of Prolonged Sevoflurane Exposure on Developing Monkey
      Brain: From Abnormal Lipid Metabolism to Neuronal Damage.
AB  - Sevoflurane is a volatile anesthetic that has been widely used in general
      anesthesia, yet its safety in pediatric use is a public concern. This study
      sought to evaluate whether prolonged exposure of infant monkeys to a clinically
      relevant concentration of sevoflurane is associated with any adverse effects on
      the developing brain. Infant monkeys were exposed to 2.5% sevoflurane for 9 h,
      and frontal cortical tissues were harvested for DNA microarray, lipidomics,
      Luminex protein, and histological assays. DNA microarray analysis showed that
      sevoflurane exposure resulted in a broad identification of differentially
      expressed genes (DEGs) in the monkey brain. In general, these genes were
      associated with nervous system development, function, and neural cell viability.
      Notably, a number of DEGs were closely related to lipid metabolism. Lipidomic
      analysis demonstrated that critical lipid components, (eg,
      phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol) were
      significantly downregulated by prolonged exposure of sevoflurane. Luminex protein
      analysis indicated abnormal levels of cytokines in sevoflurane-exposed brains.
      Consistently, Fluoro-Jade C staining revealed more degenerating neurons after
      sevoflurane exposure. These data demonstrate that a clinically relevant
      concentration of sevoflurane (2.5%) is capable of inducing and maintaining an
      effective surgical plane of anesthesia in the developing nonhuman primate and
      that a prolonged exposure of 9 h resulted in profound changes in gene expression,
      cytokine levels, lipid metabolism, and subsequently, neuronal damage. Generally,
      sevoflurane-induced neuronal damage was also associated with changes in lipid
      content, composition, or both; and specific lipid changes could provide insights
      into the molecular mechanism(s) underlying anesthetic-induced neurotoxicity and
      may be sensitive biomarkers for the early detection of anesthetic-induced
      neuronal damage.

PMID- 26206147
TI  - Hypoxia-Inducible Factor-1: A Critical Player in the Survival Strategy of
      Stressed Cells.
AB  - HIF-1 activation has been well known as an adaptive strategy to hypoxia. Recently
      it became clear that hypoxia was often accompanied by insufficient supply of
      glucose or amino acids as a common result of poor circulation that frequently
      occurs in solid tumors and ischemic lesions, creating a mixed nutrient
      insufficiency. In response to nutrient insufficiency, stressed cells elicit
      survival strategies including activation of AMPK and HIF-1 to cope with the
      stress. Particularly, in solid tumors, HIF-1 promotes cell survival and
      migration, stimulates angiogenesis, and induces resistance to radiation and
      chemotherapy. Interestingly, radiation and some chemotherapeutics are reported to
      trigger the activation of AMPK. Here we discuss the recent advances that may
      potentially link the stress responsive mechanisms including AMPK activation, ATF4
      activation and the enhancement of Hsp70/Hsp90 function to HIF-1 activation.
      Potential implication and application of the stress-facilitated HIF-1 activation
      in solid tumors and ischemic disorders will be discussed. A better understanding
      of HIF-1 activation in cells exposed to stresses is expected to facilitate the
      design of therapeutic approaches that specifically modulate cell survival
      strategy.

PMID- 26206151
TI  - Structural plasticity of green fluorescent protein to amino acid deletions and
      fluorescence rescue by folding-enhancing mutations.
AB  - BACKGROUND: Green fluorescent protein (GFP) and its derivative fluorescent
      proteins (FPs) are among the most commonly used reporter systems for studying
      gene expression and protein interaction in biomedical research. Most commercially
      available FPs have been optimized for their oligomerization state to prevent
      potential structural constraints that may interfere with the native function of
      fused proteins. Other approach to reducing structural constraints may include
      minimizing the structure of GFPs. Previous studies in an enhanced GFP variant
      (EGFP) identified a series of deletions that can retain GFP fluorescence. In this
      study, we interrogated the structural plasticity of a UV-optimized GFP variant
      (GFP(UV)) to amino acid deletions, characterized the effects of deletions and
      explored the feasibility of rescuing the fluorescence of deletion mutants using
      folding-enhancing mutations. METHODS: Transposon mutagenesis was used to screen
      amino acid deletions in GFP that led to fluorescent and nonfluorescent
      phenotypes. The fluorescent GFP mutants were characterized for their whole-cell
      fluorescence and fraction soluble. Fluorescent GFP mutants with internal
      deletions were purified and characterized for their spectral and folding
      properties. Folding-ehancing mutations were introduced to deletion mutants to
      rescue their compromised fluorescence. RESULTS: We identified twelve amino acid
      deletions that can retain the fluorescence of GFP(UV). Seven of these deletions
      are either at the N- or C- terminus, while the other five are located at internal
      helices or strands. Further analysis suggested that the five internal deletions
      diminished the efficiency of protein folding and chromophore maturation. Protein
      expression under hypothermic condition or incorporation of folding-enhancing
      mutations could rescue the compromised fluorescence of deletion mutants. In
      addition, we generated dual deletion mutants that can retain GFP fluorescence.
      CONCLUSION: Our results suggested that a "size-minimized" GFP may be developed by
      iterative incorporation of amino acid deletions, followed by fluorescence rescue
      with folding-enhancing mutations.

PMID- 26206152
TI  - Functional role of miR-10b in tamoxifen resistance of ER-positive breast cancer
      cells through down-regulation of HDAC4.
AB  - BACKGROUND: For breast cancer patients diagnosed with estrogen receptor (ER)
      positive tumors, treatment with tamoxifen is the gold standard. A significant
      number of patients, however, develop resistance to tamoxifen, and management of
      such tamoxifen-resistant patients is a major clinical challenge. With an eye to
      identify novel targets for the treatment of tamoxifen-resistant tumors, we
      observed that tamoxifen-resistant cells derived from ER-positive MCF-7 cells
      (MCF7TR) exhibit an increased expression of microRNA-10b (miR-10b). A role of miR
      10b in drug-resistance of breast cancer cells has never been investigated,
      although its is very well known to influence invasion and metastasis. METHODS: To
      dileneate a role of miR-10b in tamoxifen-resistance, we over-expressed miR-10b in
      MCF-7 cells and down-regulated its levels in MCF7TR cells. The mechanistic role
      of HDAC4 in miR-10b-mediated tamoxifen resistance was studied using HDAC4 cDNA
      and HDAC4-specific siRNA in appropriate models. RESULTS: Over-expression of miR
      10b in ER-positive MCF-7 and T47D cells led to increased resistance to tamoxifen
      and an attenuation of tamoxifen-mediated inhibition of migration, whereas down
      regulation of miR-10b in MCF7TR cells resulted in increased sensitivity to
      tamoxifen. Luciferase assays identified HDAC4 as a direct target of miR-10b. In
      MCF7TR cells, we observed down-regulation of HDAC4 by miR-10b. HDAC4-specific
      siRNA-mediated inactivation of HDAC4 in MCF-7 cells led to acquisition of
      tamoxifen resistance, and, moreover, reduction of HDAC4 in MCF7TR cells by HDAC4
      specific siRNA transfection resulted in further enhancement of tamoxifen
      resistance. CONCLUSIONS: We propose miR-10b-HDAC4 nexus as one of the molecular
      mechanism of tamoxifen resistance which can potentially be expolited as a novel
      targeted therapeutic approach for the clinical management of tamoxifen-resistant
      breast cancers.

PMID- 26206153
TI  - Informal employment and health status in Central America.
AB  - BACKGROUND: Informal employment is assumed to be an important but seldom studied
      social determinant of health, affecting a large number of workers around the
      world. Although informal employment arrangements constitute a permanent,
      structural pillar of many labor markets in low- and middle-income countries,
      studies about its relationship with health status are still scarce. In Central
      America more than 60% of non-agricultural workers have informal employment.
      Therefore, we aimed to assess differences in self-perceived and mental health
      status of Central Americans with different patterns of informal and formal
      employment. METHODS: Employment profiles were created by combining employment
      relations (employees, self-employed, employers), social security coverage
      (yes/no) and type of contract--only for employees--(written, oral, none), in a
      cross-sectional study of 8,823 non-agricultural workers based on the I Central
      American Survey of Working Conditions and Health of 2011. Using logistic
      regression models, adjusted odds ratios (aOR) by country, age and occupation, of
      poor self-perceived and mental health were calculated by sex. Different models
      were first fitted separately for the three dimensions of employment conditions,
      then for employment profiles as independent variables. RESULTS: Poor self
      perceived health was reported by 34% of women and 27% of men, and 30% of women
      and 26% of men reported poor mental health. Lack of social security coverage was
      associated with poor self-perceived health (women, aOR: 1.38, 95% CI: 1.13-1.67;
      men, aOR: 1.36, 95% CI: 1.13-1.63). Almost all employment profiles with no social
      security coverage were significantly associated with poor self-perceived and poor
      mental health in both sexes. CONCLUSIONS: Our results show that informal
      employment is a significant factor in social health inequalities among Central
      American workers, which could be diminished by policies aimed at increasing
      social security coverage.

PMID- 26206154
TI  - Cardiac dosimetric evaluation of deep inspiration breath-hold level variances
      using computed tomography scans generated from deformable image registration
      displacement vectors.
AB  - There is a reduction in cardiac dose for left-sided breast radiotherapy during
      treatment with deep inspiration breath-hold (DIBH) when compared with treatment
      with free breathing (FB). Various levels of DIBH may occur for different
      treatment fractions. Dosimetric effects due to this and other motions are a major
      component of uncertainty in radiotherapy in this setting. Recent developments in
      deformable registration techniques allow displacement vectors between various
      temporal and spatial patient representations to be digitally quantified. We
      propose a method to evaluate the dosimetric effect to the heart from variable
      reproducibility of DIBH by using deformable registration to create new anatomical
      computed tomography (CT) scans. From deformable registration, 3-dimensional
      deformation vectors are generated with FB and DIBH. The obtained deformation
      vectors are scaled to 75%, 90%, and 110% and are applied to the reference image
      to create new CT scans at these inspirational levels. The scans are then imported
      into the treatment planning system and dose calculations are performed. The
      average mean dose to the heart was 2.5Gy (0.7 to 9.6Gy) at FB, 1.2Gy (0.6 to
      3.8Gy, p < 0.001) at 75% inspiration, 1.1Gy (0.6 to 3.1Gy, p = 0.004) at 90%
      inspiration, 1.0Gy (0.6 to 3.0Gy) at 100% inspiration or DIBH, and 1.0Gy (0.6 to
      2.8Gy, p = 0.019) at 110% inspiration. The average mean dose to the left anterior
      descending artery (LAD) was 19.9Gy (2.4 to 46.4Gy), 8.6Gy (2.0 to 43.8Gy, p <
      0.001), 7.2Gy (1.9 to 40.1Gy, p = 0.035), 6.5Gy (1.8 to 34.7Gy), and 5.3Gy (1.5
      to 31.5Gy, p < 0.001), correspondingly. This novel method enables numerous
      anatomical situations to be mimicked and quantifies the dosimetric effect they
      have on a treatment plan. 

PMID- 26206156
TI  - Redox-Active Metal-Organic Frameworks: Highly Stable Charge-Separated States
      through Strut/Guest-to-Strut Electron Transfer.
AB  - Molecular organization of donor and acceptor chromophores in self-assembled
      materials is of paramount interest in the field of photovoltaics or mimicry of
      natural light-harvesting systems. With this in mind, a redox-active porous
      interpenetrated metal-organic framework (MOF), {[Cd(bpdc)(bpNDI)]?4.5 H2 O?DMF}n
      (1) has been constructed from a mixed chromophoric system. The MU-oxo-bridged
      secondary building unit, {Cd2 (MU-OCO)2 }, guides the parallel alignment of bpNDI
      (N,N'-di(4-pyridyl)-1,4,5,8-naphthalenediimide) acceptor linkers, which are
      tethered with bpdc (bpdcH2 =4,4'-biphenyldicarboxylic acid) linkers of another
      entangled net in the framework, resulting in photochromic behaviour through inter
      net electron transfer. Encapsulation of electron-donating aromatic molecules in
      the electron-deficient channels of 1 leads to a perfect donor-acceptor co-facial
      organization, resulting in long-lived charge-separated states of bpNDI.
      Furthermore, 1 and guest encapsulated species are characterised through
      electrochemical studies for understanding of their redox properties. 

PMID- 26206157
TI  - Improving soil-transmitted helminths detection in chronic kidney disease
      patients.

PMID- 26206155
TI  - Identifying genomic changes associated with insecticide resistance in the dengue
      mosquito Aedes aegypti by deep targeted sequencing.
AB  - The capacity of mosquitoes to resist insecticides threatens the control of
      diseases such as dengue and malaria. Until alternative control tools are
      implemented, characterizing resistance mechanisms is crucial for managing
      resistance in natural populations. Insecticide biodegradation by detoxification
      enzymes is a common resistance mechanism; however, the genomic changes underlying
      this mechanism have rarely been identified, precluding individual resistance
      genotyping. In particular, the role of copy number variations (CNVs) and
      polymorphisms of detoxification enzymes have never been investigated at the
      genome level, although they can represent robust markers of metabolic resistance.
      In this context, we combined target enrichment with high-throughput sequencing
      for conducting the first comprehensive screening of gene amplifications and
      polymorphisms associated with insecticide resistance in mosquitoes. More than 760
      candidate genes were captured and deep sequenced in several populations of the
      dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and
      contrasted resistance levels to the insecticide deltamethrin. CNV analysis
      identified 41 gene amplifications associated with resistance, most affecting
      cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis
      detected more than 30,000 variants and strong selection footprints in specific
      genomic regions. Combining Bayesian and allele frequency filtering approaches
      identified 55 nonsynonymous variants strongly associated with resistance. Both
      CNVs and polymorphisms were conserved within regions but differed across
      continents, confirming that genomic changes underlying metabolic resistance to
      insecticides are not universal. By identifying novel DNA markers of insecticide
      resistance, this study opens the way for tracking down metabolic changes
      developed by mosquitoes to resist insecticides within and among populations. 

PMID- 26206158
TI  - Rationale, Design, and Baseline Characteristics of the EPICOR Asia Study (Long
      tErm follow-uP of antithrombotic management patterns In Acute CORonary Syndrome
      patients in Asia).
AB  - BACKGROUND: In-hospital and postdischarge mortality for acute coronary syndromes
      (ACS) vary across Asia and remain generally poorer than globally. The
      relationship between real-life antithrombotic management patterns (AMPs) and ACS
      related outcomes in Asia is unclear. METHODS: EPICOR Asia (Long-tErm follow-uP of
      antithrombotic management patterns In acute CORonary syndrome patients in Asia)
      (NCT01361386) is a prospective, multinational, observational study of patients
      discharged after hospitalization for an ACS, with 2-year follow-up. The aim is to
      describe short- and long-term (up to 2 years post-index event) AMPs in patients
      hospitalized for ACS and to record clinical outcomes, healthcare resource use,
      and self-reported health status. Pre- and in-hospital management, AMPs, and
      associated outcomes, with particular focus on ischemic and bleeding events, will
      be recorded during the 2-year follow up. RESULTS: Between June 2011 and May 2012,
      13 005 patients were enrolled. From these, 12 922 patients surviving an ACS (6616
      with STEMI, 2570 with NSTEMI, and 3736 with UA) were eligible for inclusion from
      219 hospitals across 8 countries and regions in Asia: China (n = 8214), Hong Kong
      (n = 177), India (n = 2468), Malaysia (n = 100), Singapore (n = 93), South Korea
      (n = 705), Thailand (n = 957), and Vietnam (n = 208). CONCLUSIONS: EPICOR Asia
      will provide information regarding clinical management and AMPs for ACS patients
      in Asia. Impact of AMPs on clinical outcomes, healthcare resource use, and self
      reported health status both during hospitalization and up to 2 years after
      discharge will also be described.

PMID- 26206159
TI  - Male Contraception: Research, New Methods, and Implications for Marginalized
      Populations.
AB  - The majority of research on contraception has focused on manipulating the female
      reproductive system. Recent studies have identified novel contraceptives for
      males, including hormonal- and nonhormonal-based therapeutics. Although these new
      contraceptives are still undergoing clinical trials, their development and
      potential future use in society necessitate serious consideration of their
      implications for reproductive health. Through my analysis of the research
      conducted on male contraception over time and the current therapeutics available,
      it is clear that male contraception has the potential to shift societal gender
      dynamics and provide males with greater control over their own reproduction. This
      article also identifies the implications of these novel contraceptives for
      marginalized populations, especially men of color and men of lower socioeconomic
      positions. To overcome barriers to contraception among these populations, public
      policy efforts are needed in order to motivate the development of programs that
      facilitate coverage of these new male contraceptives by health plans and to
      increase their availability to underserved communities. Health care providers
      will be responsible for educating patients about these novel male contraception
      options and the need to continue using existing methods (e.g., condoms) in order
      to prevent sexually transmitted infections. This article analyzes the research
      conducted on male contraception and identifies the implications of these novel
      therapeutics for marginalized groups of men in the United States to identify the
      interventions that will be necessary to help ensure that all men have access to
      these promising scientific innovations.

PMID- 26206160
TI  - Barriers to Recruiting Men Into Chronic Disease Prevention and Management
      Programs in Rural Areas: Perspectives of Program Delivery Staff.
AB  - Chronic disease is becoming increasingly prevalent in Canada. Many of these
      diseases could be prevented by adoption of healthy lifestyle habits including
      physical activity and healthy eating. Men, especially those in rural areas, are
      disproportionately affected by chronic disease. However, men are often
      underrepresented in community-based chronic disease prevention and management
      (CDPM) programs, including those that focus on physical activity and/or healthy
      eating. The purpose of this study was to explore the experiences and perceptions
      of program delivery staff regarding the challenges in recruitment and
      participation of men in physical activity and healthy eating programs in rural
      communities, and suggestions for improvement. Semistructured interviews were
      conducted by telephone with 10 CDPM program delivery staff from rural communities
      in Southwest Ontario, Canada. Time and travel constraints, relying on spouses,
      and lack of male program leaders were cited as barriers that contributed to low
      participation levels by men in CDPM programs. Hiring qualified male instructors
      and engaging spouses were offered as strategies to increase men's participation.
      The results of this study highlight many of the current issues faced by rural
      health organizations when offering CDPM programming to men. Health care
      organizations and program delivery staff can use the recommendations in this
      report to improve male participation levels.

PMID- 26206162
TI  - Chronic Disease and Depression Among Hispanic Americans: Reconceptualizing the
      Masculine Self.
AB  - Hispanic Americans are the fastest growing minority group in the United States.
      They face a distinct set of health challenges, resulting in persistent health
      disparities. Chronic disease self-management programs hold promise in addressing
      individual-level, behavioral risks factors, such as dietary habits and physical
      activity patterns. In light of the unique barriers Hispanic men face, including
      low participation in evidence-based health intervention research, this article
      argues for a gendered perspective when approaching Hispanic men's physical and
      mental health needs. Through the analysis of data collected from male-only focus
      groups (N = 3, n = 15) with Hispanic Americans in west central Florida, this
      study identified that masculine identity is influenced by chronic disease and
      comorbid depression status. Diagnosis with a chronic disease and/or depression is
      accompanied by lifestyle adaptations, activity restrictions, and changes in
      income and health care demands that can undermine traditional notions of Hispanic
      masculinity. Consequently, masculine identity is associated with self-management
      strategies in complex ways. Public health interventions aimed at addressing
      comorbid chronic disease and depression among Hispanic men must take into
      consideration the role of gender identity and relevant conceptualizations of
      masculinity in order to better serve this underserved and understudied
      population.

PMID- 26206161
TI  - Erectile Dysfunction: A Review of Historical Treatments With a Focus on the
      Development of the Inflatable Penile Prosthesis.
AB  - Erectile dysfunction has been a concern for men since the beginning of written
      history. For many men it can lead to severe psychological distress and
      humiliation. The treatment of erectile dysfunction has advanced significantly
      over the past 200 years. Men today are presented with many more viable therapy
      options leading to improved efficacy and more satisfactory sex lives. The
      objective of this article is to explore historical options for the treatment of
      erectile dysfunction, with particular emphasis on the development and progression
      of the inflatable penile prosthesis.

PMID- 26206163
TI  - Intersphincteric approach for rectourethral fistulas following radical
      prostatectomy.
AB  - BACKGROUND: Rectourethral fistula is a challenging complication of radical
      retropubic prostatectomy. Several treatments have been proposed, with varying
      outcomes. The available data are difficult to interpret, because patient and
      disease characteristics differ significantly among reports. Details of long-term
      follow-up and functional status are rarely provided. We describe a technique of
      rectourethral fistula repair via an intersphincteric route. METHODS: Preoperative
      workup included proctoscopy and urethrocystography. All patients already had a
      stoma at the time of fistula repair. Mechanical cleansing of the bowel distal to
      the colostomy was routinely performed, and perioperative antibiotic prophylaxis
      was administered. Patients were placed in the lithotomy position. Under spinal
      anesthesia, a curvilinear anteanal incision was made, to expose the external
      sphincter. The anterior portion of the external sphincter was gently displaced
      along half of its circumference. The anterior rectal wall was sharply dissected
      free from the urethra, approximately up to 2 cm above the fistula level through
      the intersphincteric plane. The fistula was identified. The surrounding tissues
      were mobilized to obtain a tension-free repair of the urethral defect, using a
      single row of 4-0 polyglactin transverse, interrupted sutures. Transanally, a U
      shaped full-thickness rectal flap was advanced and sutured with 3-0 monofilament
      interrupted sutures to cover the rectal opening, and care was taken to ensure
      that the two suture lines were in different planes. The catheter was left in
      place for 4 weeks. Patients were evaluated at 3-month follow-up for stoma
      closure. RESULTS: We successfully treated five patients. Only one minor
      complication was observed (surgical site infection). Stomas were taken down
      uneventfully. After a median follow-up duration of 2 years (range 2-3 years), no
      patients had fistula recurrence or impaired continence. CONCLUSIONS:
      Intersphincteric repair should be considered as an effective option in patients
      with iatrogenic rectourethral fistulas. This technique offers several advantages
      over alternative procedures that require more extensive approaches or invasive
      manipulation of the anal sphincters.

PMID- 26206165
TI  - Ultra-stable small diameter hybrid transition metal dichalcogenide nanotubes X-M
      Y (X, Y = S, Se, Te; M = Mo, W, Nb, Ta): a computational study.
AB  - Similar to graphene and hexagonal boron nitride (h-BN), the two-dimensional (2D)
      transition metal dichalcogenide (TMD) can be rolled into one-dimensional (1D)
      nanotubes. While, owing to their three-atom-thick structure, the large energy
      penalty greatly hinders the synthesis of small diameter TMD nanotubes. Here we
      propose the synthesis of hybrid TMD nanotubes with different chalcogens on each
      side (X-TM-Y) by self-assembly rolling up. Our calculations indicate that the
      tube formation can be driven by the relaxation of the intrinsic strain in X-TM-Y
      and the synthesis of the small hybrid nanotubes with diameter of ~2.0 nm is
      possible. The rich variety of polymorphs exhibit unique and tunable electronic
      properties. Our finding opens a door synthesize hybrid small diameter TMD
      nanotubes for various applications. 

PMID- 26206164
TI  - A free anterolateral thigh flap and iliotibial band for reconstruction of soft
      tissue defects at children's feet and ankles.
AB  - BACKGROUND AND PURPOSE: High-energy injury to children caused by a traffic
      accident is usually characterised by extensive soft tissue defects with exposure
      or loss of tendons and bone at the foot. Segmental loss of the Achilles tendon
      along with soft tissue defects is a great challenge for microsurgical
      reconstruction. Free anterolateral thigh (ALT) flap is indicated for
      reconstruction of such defects because limited local tissues are available.
      Additionally, iliotibial band in the donor area can be used to reconstruct the
      damaged tendon. MATERIALS AND METHODS: Here we described our successful
      management of 25 paediatric patients with such high-energy injury at feet and
      ankles in one-stage transplantation of a free ALT flap and an iliotibial band
      from January 2008 to January 2013. The tendon defect, ranging from 3 to 16cm in
      length, was reconstructed with an iliotibial band. The flaps ranged from 5 to
      12cm in width and 8 to 18cm in length. RESULTS: All the flaps survived completely
      and no donor site complications were observed. In two flaps there was a small
      area of distal necrosis which was healed by dressing changes. The mean follow-up
      time was 14.2 months (from 6 to 24 months). Limb function was assessed using the
      Maryland Foot Score. The excellent and good rate was 92%. CONCLUSIONS: We believe
      a free ALT flap is ideal for reconstruction of massive soft tissue defects at the
      foot and ankle in children and an iliotibial band from the same donor site can be
      used for reconstruction of a damaged tendon.

PMID- 26206166
TI  - Societal views and animal welfare science: understanding why the modified cage
      may fail and other stories.
AB  - The innovations developed by scientists working on animal welfare are often not
      adopted in practice. In this paper, we argue that one important reason for this
      failure is that the solutions proposed do not adequately address the societal
      concerns that motivated the original research. Some solutions also fail because
      they do not adequately address perceived constraints within the industry. Using
      examples from our own recent work, we show how research methods from the social
      sciences can address both of these limitations. For example, those who persist in
      tail-docking cattle (despite an abundance of evidence showing that the practice
      has no benefits) often justify their position by citing concern for cow
      cleanliness. This result informs the nature of new extension efforts directed at
      farmers that continue to tail dock, suggesting that these efforts will be more
      effective if they focus on providing producers with methods (of proven efficacy)
      for keeping cows clean. Work on pain mitigation for dehorning shows that some
      participants reluctant to provide pain relief believe that the pain from this
      procedure is short lasting and has little impact on the calf. This result informs
      the direction of new biological research efforts to understand both the magnitude
      and duration of any suffering that result from this type of procedure. These, and
      other examples, illustrate how social science methodologies can document the
      shared and divergent values of different stakeholders (to ensure that proposed
      solutions align with mainstream values), beliefs regarding the available evidence
      (to help target new scientific research that meets the perceived gaps), and
      barriers in implementing changes (to ease adoption of ideas by addressing these
      barriers). 

PMID- 26206167
TI  - Reliability of maximal grip strength measurements and grip strength recovery
      following a stroke.
AB  - STUDY DESIGN: Clinical measurement. PURPOSE: The test-retest reliability of
      maximal grip strength measurements (MGSM) is examined in subjects for 12 weeks
      post-stroke together with maximal grip strength recovery and the maximal-grip and
      upper-extremity strength measurements' relationship with capacity and performance
      test scores. METHODS: A Jamar dynamometer and the Motricity Index (MI) were used
      for strength measurements. The Chedoke Arm and Hand Activity Inventory and
      ABILHAND questionnaire for evaluating capacities and performances. RESULTS: MGSM
      were reliable (Intraclass Correlation Coefficients = 0.97-0.99, Minimal
      Detectable Differences = 2.73-4.68 kg). Among the 34 participants, 47% did not
      have a measurable grip strength one week post-stroke but 50% of these recovered
      some strength within the first eight weeks. The MGSM and MI scores were
      correlated with scores of tests of capacity and performance (Spearman's Rank
      Correlation Coefficients = 0.69-0.94). CONCLUSIONS: MGSM are reliable in the
      first weeks after a stroke. LEVEL OF EVIDENCE: N/A.

PMID- 26206168
TI  - A new method for measuring forearm rotation using a modified finger goniometer.
AB  - In this manuscript, the authors describe the challenges with measuring forearm
      range of motion, and propose a new method for obtaining this measurement. Pros,
      cons, and future research directions are discussed.--Victoria Priganc, PhD, OTR,
      CHT, CLT, Practice Forum Editor.

PMID- 26206169
TI  - Decline of Yangtze River water and sediment discharge: Impact from natural and
      anthropogenic changes.
AB  - The increasing impact of both climatic change and human activities on global
      river systems necessitates an increasing need to identify and quantify the
      various drivers and their impacts on fluvial water and sediment discharge. Here
      we show that mean Yangtze River water discharge of the first decade after the
      closing of the Three Gorges Dam (TGD) (2003-2012) was 67 km(3)/yr (7%) lower than
      that of the previous 50 years (1950-2002), and 126 km(3)/yr less compared to the
      relatively wet period of pre-TGD decade (1993-2002). Most (60-70%) of the decline
      can be attributed to decreased precipitation, the remainder resulting from
      construction of reservoirs, improved water-soil conservation and increased water
      consumption. Mean sediment flux decreased by 71% between 1950-1968 and the post
      TGD decade, about half of which occurred prior to the pre-TGD decade.
      Approximately 30% of the total decline and 65% of the decline since 2003 can be
      attributed to the TGD, 5% and 14% of these declines to precipitation change, and
      the remaining to other dams and soil conservation within the drainage basin.
      These findings highlight the degree to which changes in riverine water and
      sediment discharge can be related with multiple environmental and anthropogenic
      factors. 

PMID- 26206170
TI  - Unfreezing cognitions during an intractable conflict: Does an external incentive
      for negotiating peace and (low levels of) collective angst increase information
      seeking?
AB  - A core feature of intractable conflicts is the tendency to cognitively freeze on
      existing, pro-ingroup beliefs. In three experiments, conducted in the context of
      the Palestinian-Israeli conflict, we tested the idea that an external incentive
      for negotiating peace helps unfreeze cognitions. In Experiment 1, making salient
      that peace with the Palestinians would reduce the Iranian nuclear threat (an
      external incentive) led to a process of unfreezing. In Experiment 2, we examined
      whether collective angst as an emotional sentiment (i.e., concern for the
      ingroup's future vitality as a temporally stable emotional disposition) moderated
      the aforementioned external incentive-cognitive unfreezing link. As predicted,
      external incentive salience promoted cognitive unfreezing, but only among people
      low in collective angst (i.e., people who are not concerned for the ingroup's
      future). In Experiment 3, we sought to replicate the results of Experiment 2.
      However, socio-political forces (i.e., a significant upswing in tensions between
      Palestinians and Israelis) likely served to freeze cognitions to such an extent
      that thawing was not possible by the means demonstrated in Experiments 1 and 2.
      The importance of confidence in a peace process is discussed in the context of
      efforts to unfreeze cognitions during an intractable conflict. 

PMID- 26206171
TI  - The importance of dementia support groups.

PMID- 26206172
TI  - A historical exploration of Indian diets and a possible link to insulin
      resistance syndrome.
AB  - BACKGROUND: Insulin resistance syndrome, especially with diabetes, is becoming
      increasingly prevalent in India. The increasing consumption of low-fibre and
      refined carbohydrates is thought to be related to the increased risk of insulin
      resistance syndrome. AIM: The aim was to study the history of eating behaviours
      in India; the patterns (macronutrients, frequency, and quantity) of food
      consumption amongst ancient, medieval and modern Indians; and the evolution of a
      primarily low-fibre and refined-carbohydrate diet. METHODS: The ancient dietary
      laws of India, historical documents, and ancient and medieval literature and
      poetry, spanning more than 2000 years, were studied. These data were compared
      with modern diets among people of different geographical regions, religions and
      social strata using the National Nutritional Database of the US Department of
      Agriculture (USDA) for analysis. CONCLUSIONS: The data presented shows a gradual
      shift over the centuries from the Pastoral Age diet of large quantities of high
      fibre carbohydrates, small amounts of digestible carbohydrates, moderate fats,
      moderate proteins, to an increasing and frequent intake of high-fibre
      carbohydrates associated with significant drop in protein and fat consumption
      between 1775 and 1947. From 1947 onwards there has been an increase in the
      frequency of intake and quantities of low-fibre and refined carbohydrates, and
      fats with protein intake improving only marginally.

PMID- 26206173
TI  - Eating to live or living to eat? Exploring the causal attributions of self
      perceived food addiction.
AB  - Previous studies indicate that many people perceive themselves to be addicted to
      food. However, little is known about how the concept of 'food addiction' is
      defined amongst members of the lay public. The current study examined beliefs
      about the cognitive and behavioural manifestations of food addiction.
      Participants (N = 210) completed an internet-delivered questionnaire in which
      they indicated whether or not they perceived themselves to be a food addict and
      provided a brief explanation for their response. Over a quarter of participants
      (28%) perceived themselves to be food addicts and self-diagnosis was predicted by
      increased BMI and younger age, but not by gender. Thematic analysis was conducted
      to explore the causal attributions provided by self-perceived food addicts and
      non-addicts. Six characteristics were identified: 1) Reward-driven eating (i.e.
      eating for psychological rather than physiological reasons), 2) A functional or
      psychological preoccupation with food, 3) A perceived lack of self-control around
      food, 4) Frequent food cravings, 5) Increased weight or an unhealthy diet, and 6)
      A problem with a specific type of food. The emergent themes, and their frequency,
      did not differ between self-perceived food addicts and non-addicts. However, self
      perceived food addicts and non-addicts reported divergent cognitions, behaviours
      and attitudes within each common theme. This study is the first to provide
      qualitative insight into beliefs about food addiction in both self-perceived food
      addicts and non-addicts. The findings appear to reflect a view of food addiction
      that is identifiable through several core behaviours.

PMID- 26206174
TI  - Predicting gender differences in liking for vegetables and preference for a
      variety of vegetables among 11-year-old children.
AB  - We studied the factors that predict liking for vegetables and preference for a
      variety of vegetables among schoolchildren. Additionally, we examined if there
      were gender differences in the predictors that explain the hypothesized higher
      scores in liking vegetables and preferences among girls. The data from the PRO
      GREENS project included 424 Finnish children (response rate 77%) aged 11 to 12.
      The children completed validated measures about social and environmental factors
      related to their liking for vegetables and preferences both at baseline 2009 and
      follow-up 2010. The associations were examined with regression and mediation
      analyses. The strongest predictors of both girls' and boys' liking and
      preferences were higher levels of eating vegetables together with the family,
      previous vegetable intake and a lower level of perceived barriers. Liking was
      additionally predicted by a lower level of parental demand that their child
      should eat vegetables. Girls reported higher levels of liking and preferences in
      the follow-up. This gender difference was mainly explained by girls' lower level
      of perceived barriers related to vegetable intake and girls' higher previous
      vegetable intake. Interventions that aim to increase the low vegetable intake
      among boys by increasing their liking for vegetables and preference for a variety
      of vegetables could benefit from targeting perceived barriers, namely boys'
      perception and values concerning the consumption of vegetables. 

PMID- 26206175
TI  - Mealtime behaviors associated with consumption of unfamiliar foods by young
      children with autism spectrum disorder.
AB  - Parent and child mealtime behaviors associated with consumption of unfamiliar
      foods by children with ASD were examined. Families of 38 children aged 2 through
      8 years old and diagnosed with ASD videotaped a typical home mealtime during
      which parents presented the child with an unfamiliar food and mealtime behaviors
      were subsequently coded through an observational coding system. The child taking
      sips of their drink was the only behavior related to whether the child took a
      bite of the unfamiliar food throughout the course of the meal. Parent direct
      commands and parents feeding the child were related to greater frequency of
      subsequent bites in a close temporal window, while child play, the child being
      away from the table, and child talk about things other than food related to lower
      frequencies of subsequent bites. Clinical interventions for food selectivity in
      children with ASD might provide parents education on effective mealtime parenting
      strategies and decreasing inappropriate child mealtime behaviors. 

PMID- 26206176
TI  - The effect of gender and genetic polymorphisms on matrix metalloprotease (MMP)
      and tissue inhibitor (TIMP) plasma levels in different infectious and non
      infectious conditions.
AB  - Matrix metalloproteases (MMPs) are increased in different infections due to their
      role in controlling immune responses and are regulated by tissue inhibitors
      (TIMPs). Different MMP promoter single nucleotide polymorphisms (SNPs) induce
      changes in MMP genes, mRNA and protein expression. Gender might also modify MMP
      plasma levels. In order to determine the weight of these variables on MMP
      secretion we studied MMP-1, -2, -3, -8, -9, -10, -13 and TIMP-1, -2, -4 plasma
      levels in 90 patients with severe bacterial sepsis, 102 with anti-retroviral
      (ARV)-treated HIV monoinfection, 111 with ARV-treated HIV-hepatitis C virus (HCV)
      co-infection and 86 non-infected controls (45 stroke and 41 trauma patients). MMP
      1(-1607 1G/2G), MMP-3(-1612 5A/6A), MMP-8(-799C/T), MMP-9(-1562 C/T) and MMP-13(
      77A/G) SNPs were genotyped. MMP-3 plasma levels were significantly higher in men
      than in women in each diagnostic group, and MMP-3 SNP allele 6A carriers also had
      higher levels than allele 5A carriers, an effect that was magnified by sepsis.
      Independent predictors of higher MMP-3 levels were male gender (P = 0.0001), MMP
      3(-1612 5A/6A) SNP (P = 0.001), higher levels of TIMP-4 (P = 0.004) and MMP-8 (P
      = 0.006) and lower levels of MMP-1 (P = 0.03) by multivariate analysis. No strong
      associations with gender or SNPs were observed for other MMPs or TIMPs. In
      conclusion, male gender and MMP-3(-1612 5A/6A) 6A allele carriage increased MMP-3
      plasma levels significantly, especially in patients with severe bacterial sepsis.
      This confounding gender effect needs to be addressed when evaluating MMP-3 plasma
      levels in any infectious or non-infectious condition.

PMID- 26206177
TI  - Evaluation of the efficacy of six supraglottic devices for airway management in
      dark conditions: a crossover randomized simulation trial.
AB  - PURPOSE: During out-of-hospital cardiopulmonary resuscitation, several factors
      can render tracheal intubation more difficult, such as when rescuers must secure
      the airway in complete darkness or with limited illumination. The purpose of this
      study was to evaluate the efficacy of six supraglottic devices (SGDs),
      ProSeal((r)) (ProSeal), Classic((r)) (Classic), Supreme((r)) (Supreme), Laryngeal
      Tube((r)) (LT), air-Q((r)) (air-Q), and i-gel((r)) (i-gel), for airway management
      under light and dark conditions using a manikin. METHODS: Seventeen novice
      doctors and 15 experienced doctors performed insertion of six SGDs under light
      and dark conditions using an adult manikin. Insertion time, successful
      ventilation rate, and subjective insertion difficulty on a visual analogue scale
      (VAS) were measured. RESULTS: Both novice and experienced doctors had a
      significantly lower ventilation success rate in the dark than in the light when
      ProSeal and Classic were used, but not with the other four SGDs. Novice doctors
      required a significantly longer insertion time in the dark than in the light with
      all SGDs. Experienced doctors required a significantly longer insertion time in
      the dark than in the light with ProSeal or Classic, but not with the other four
      SGDs. VAS was significantly higher for both novice and experienced doctors when
      ProSeal and Classic were used, as compared with the other four SGDs in the dark.
      CONCLUSIONS: Compared to ProSeal and Classic, Supreme, i-gel, LT, and air-Q are
      more effective for airway management in the dark. Our findings suggest that
      anatomically shaped SGDs may help novice doctors secure the airway under dark
      conditions.

PMID- 26206178
TI  - The centrally projecting Edinger-Westphal nucleus--I: Efferents in the rat brain.
AB  - The oculomotor accessory nucleus, often referred to as the Edinger-Westphal
      nucleus [EW], was first identified in the 17th century. Although its most well
      known function is the control of pupil diameter, some controversy has arisen
      regarding the exact location of these preganglionic neurons. Currently, the EW is
      thought to consist of two different parts. The first part [termed the
      preganglionic EW-EWpg], which controls lens accommodation, choroidal blood flow
      and pupillary constriction, primarily consists of cholinergic cells that project
      to the ciliary ganglion. The second part [termed the centrally projecting EW
      EWcp], which is involved in non-ocular functions such as feeding behavior, stress
      responses, addiction and pain, consists of peptidergic neurons that project to
      the brainstem, the spinal cord and prosencephalic regions. However, in the
      literature, we found few reports related to either ascending or descending
      projections from the EWcp that are compatible with its currently described
      functions. Therefore, the objective of the present study was to systematically
      investigate the ascending and descending projections of the EW in the rat brain.
      We injected the anterograde tracer biotinylated dextran amine into the EW or the
      retrograde tracer cholera toxin subunit B into multiple EW targets as controls.
      Additionally, we investigated the potential EW-mediated innervation of neuronal
      populations with known neurochemical signatures, such as melanin-concentrating
      hormone in the lateral hypothalamic area [LHA] and corticotropin-releasing factor
      in the central nucleus of the amygdala [CeM]. We observed anterogradely labeled
      fibers in the LHA, the reuniens thalamic nucleus, the oval part of the bed
      nucleus of the stria terminalis, the medial part of the central nucleus of the
      amygdala, and the zona incerta. We confirmed our EW-LHA and EW-CeM connections
      using retrograde tracers. We also observed moderate EW-mediated innervation of
      the paraventricular nucleus of the hypothalamus and the posterior hypothalamus.
      Our findings provide anatomical bases for previously unrecognized roles of the EW
      in the modulation of several physiologic systems. 

PMID- 26206179
TI  - Fucosylated surfactant protein-D is a biomarker candidate for the development of
      chronic obstructive pulmonary disease.
AB  - We previously reported that knockout mice for alpha1,6-fucosyltransferase (Fut8),
      which catalyzes the biosynthesis of core-fucose in N-glycans, develop emphysema
      and that Fut8 heterozygous knockout mice are more sensitive to cigarette smoke
      induced emphysema than wild-type mice. Moreover, a lower FUT8 activity was found
      to be associated with a faster decline in lung function among chronic obstructive
      pulmonary disease (COPD) patients. These results led us to hypothesize that core
      fucosylation levels in a glycoprotein could be used as a biomarker for COPD. We
      focused on a lung-specific glycoprotein, surfactant protein D (SP-D), which plays
      a role in immune responses and is present in the distal airways, alveoli, and
      blood circulation. The results of a glycomic analysis reported herein demonstrate
      the presence of a core-fucose in an N-glycan on enriched SP-D from pooled human
      sera. We developed an antibody-lectin enzyme immunoassay (EIA) for assessing
      fucosylation (core-fucose and alpha1,3/4 fucose) in COPD patients. The results
      indicate that fucosylation levels in serum SP-D are significantly higher in COPD
      patients than in non-COPD smokers. The severity of emphysema was positively
      associated with fucosylation levels in serum SP-D in smokers. Our findings
      suggest that increased fucosylation levels in serum SP-D are associated with the
      development of COPD. BIOLOGICAL SIGNIFICANCE: It has been proposed that serum SP
      D concentrations are predictive of COPD pathogenesis, but distinguishing between
      COPD patients and healthy individuals to establish a clear cut-off value is
      difficult because smoking status highly affects circulating SP-D levels. Herein,
      we focused on N-glycosylation in SP-D and examined whether or not N-glycosylation
      patterns in SP-D are associated with the pathogenesis of COPD. We performed an N
      glycomic analysis of human serum SP-D and the results show that a core-fucose is
      present in its N-glycan. We also found that the N-glycosylation in serum SP-D was
      indeed altered in COPD, that is, fucosylation levels including core-fucosylation
      are significantly increased in COPD patients compared with non-COPD smokers. The
      severity of emphysema was positively associated with fucosylation levels in serum
      SP-D in smokers. Our findings shed new light on the discovery and/or development
      of a useful biomarker based on glycosylation changes for diagnosing COPD. This
      article is part of a Special Issue entitled: HUPO 2014.

PMID- 26206180
TI  - A phosphoproteomic study reveals shp-1 cleavage reprograms LPS signaling via a PI
      3K/NF-kappaB and mTORC1 related mechanism.
AB  - The reprogrammed lipopolysaccharide (LPS) pathway has been reported to render
      patients more susceptible to the development of post-traumatic multiple organ
      dysfunction syndrome (MODS). To facilitate thorough understanding of this
      mechanism, a phosphoproteomic study was utilized to screen the potential
      signaling molecules. Interestingly, a truncated form of Src homology 2-domain
      containing tyrosine phosphatase 1 (shp-1) emerged in human THP-1 macrophages
      sequentially treated with H2O2 and LPS and not with either of the treatments
      alone. Subsequent immunoblot analysis confirmed the cleavage of shp-1 and
      reduction of shp-1 activity in rat alveolar macrophages, mast cells, and
      neutrophils. Mechanistically, calpain is essential but not sufficient for shp-1
      cleavage. In addition, shp-1 cleavage renders the activation of
      phosphatidylinositol 3-kinase (PI-3K)/nuclear factor-kappaB (NF-kappaB) and
      mechanistic target of rapamycin complex 1 (mTORC1) in macrophages, resulting in
      enhanced cytokine induced neutrophil chemoattractant (CINC) secretion, which is
      critical for neutrophil recruitment in MODS. On the other hand, shp-1 cleavage
      results in the activation of PI-3K/Akt, enhancing the survival of neutrophils.
      Collectively, these results highlight the cleavage of shp-1 as a critical event
      in reprogramming LPS pathway to promote both neutrophil recruitment and survival
      and provide a novel mechanistic framework for the investigation of the post
      traumatic MODS. 

PMID- 26206181
TI  - Proteomic analysis reveals novel common genes modulated in both replicative and
      stress-induced senescence.
AB  - Cellular senescence causes profound changes in gene expression profile. In this
      study, we used a combined 2D-DIGE and nanoLC-ESI-LIT-MS/MS approach to evaluate
      the proteomic changes occurring both in replicative and stress-induced senescence
      of human IMR90 cells. Twenty protein spots were identified as shifting their
      quantitative representation in the same direction (over- or down-represented) in
      both conditions of senescence, which were associated with 25 sequence entries.
      Dedicated experiments demonstrated that the decreased representation of a set of
      these proteins is associated with the down-regulation of the corresponding mRNAs,
      indicating that the regulation of these genes during the senescence process
      occurs at a transcriptional level. We also performed functional studies by
      silencing nine of these genes in young cells, which demonstrated that RNA
      interference-mediated knockdown of LEPRE1, LIMA1/EPLIN, MAGOHA and MAGOHB induces
      a premature senescent phenotype in IMR90 cells. Chromatin immunoprecipitation
      experiments indicated that the reduced expression of these four genes is
      associated with changes in the histone methylation pattern of their promoters, as
      proved by the occurrence of increased repressive H3K27me3 along with decreased
      active H3K4me3 marks, respectively. BIOLOGICAL SIGNIFICANCE: Cellular senescence,
      a stable form of cell cycle arrest, is recognized as a phenomenon related to
      aging and age-related pathologies as well as interfering with tumor progression.
      Gene expression changes are closely associated with the onset of senescence but
      the molecular pathways regulating this process are still poorly understood. By
      using proteomics coupled to functional studies, we here show that both
      replicative and stress-induced senescence share quantitative modification of four
      novel proteins, in addition to others already reported in the literature. When
      ectopically down-regulated, corresponding four genes induce a premature
      senescence in young cells. The observed parallelism concerning the down
      regulation of these genes both in vitro and in vivo senescent cells may foresee a
      possible biomarker role of the corresponding proteins in monitoring the
      progression of both aging and age-related diseases. In conclusion, these results
      for the first time highlight a possible role of LEPRE1, LIMA1/EPLIN, MAGOHA and
      MAGOHB in the biology of cellular senescence/aging, thus contributing to gain a
      deeper knowledge of the molecular mechanisms involved in the senescence program.

PMID- 26206183
TI  - Vatalanib sensitizes ABCB1 and ABCG2-overexpressing multidrug resistant colon
      cancer cells to chemotherapy under hypoxia.
AB  - Cancer microenvironment is characterized by significantly lower oxygen
      concentration. This hypoxic condition is known to reduce drug responsiveness to
      cancer chemotherapy via multiple mechanisms, among which the upregulation of the
      ATP-binding cassette (ABC) efflux transporters confers resistance to a wide
      variety of structurally unrelated anticancer drugs. Vatalanib (PTK787/ZK22584) is
      a multitargeted tyrosine kinase inhibitor for all isoforms of VEGFR, PDGFR and c
      Kit, which exhibit potent anticancer activity in vitro and in vivo. We
      investigated the potentiation effect of vatalanib on the anticancer activity of
      conventional cytotoxic drugs in colon cancer cell lines under both normoxic and
      hypoxic conditions. Mechanistically, vatalanib was found to inhibit ABCG2 and
      ABCB1 efflux activity, presumably by acting as a competitive inhibitor and
      interfering with their ATPase activity. Under hypoxic growth condition, ABCG2 and
      ABCB1-overexpressing cells sorted out by FACS technique as side population (SP)
      were found to be significantly more responsive to SN-38 (ABCG2 and ABCB1
      substrate anticancer drug) in the presence of vatalanib. The anchorage
      independent soft agar colony formation capacity of the SP cells was remarkably
      reduced upon treatment with a combination of SN-38 and vatalanib, compared to SN
      38 alone. However, vatalanib, at concentrations that produced the circumvention
      of the transporters-mediated resistance, did not appreciably alter ABCG2/ABCB1
      mRNA or protein expression levels or the phosphorylation of Akt and extracellular
      signal-regulated kinase (ERK1/2). Our study thus advocates the further
      investigation of vatalanib for use in combination chemotherapy to eradicate drug
      resistant cancer cells under hypoxia. 

PMID- 26206182
TI  - CCR2 inhibition sequesters multiple subsets of leukocytes in the bone marrow.
AB  - Chemokine receptor CCR2 mediates monocyte mobilization from the bone marrow (BM)
      and subsequent migration into target tissues. The degree to which CCR2 is
      differentially expressed in leukocyte subsets, and the contribution of CCR2 to
      these leukocyte mobilization from the BM are poorly understood. Using red
      fluorescence protein CCR2 reporter mice, we found heterogeneity in CCR2
      expression among leukocyte subsets in varying tissues. CCR2 was highly expressed
      by inflammatory monocytes, dendritic cells, plasmacytoid dendritic cells and NK
      cells in all tissues. Unexpectedly, more than 60% of neutrophils expressed CCR2,
      albeit at low levels. CCR2 expression in T cells, B cells and NK T cells was
      greatest in the BM compared to other tissues. Genetic CCR2 deficiency markedly
      sequestered all leukocyte subsets in the BM, with reciprocal reduction noted in
      the peripheral blood and spleen. CCR2 inhibition via treatment with CCR2
      signaling inhibitor propagermanium produced similar effects. Propagermanium also
      mitigated lipopolysaccharide-induced BM leukocyte egress. Consistent with its
      functional significance, CCR2 antibody staining revealed surface CCR2 expression
      within a subset of BM neutrophils. These results demonstrate the central role
      CCR2 plays in mediating leukocyte mobilization from the BM, and suggest a role
      for CCR2 inhibition in managing monocytes/macrophages-mediated chronic
      inflammatory conditions. 

PMID- 26206184
TI  - The multiple roles of the alpha7 nicotinic acetylcholine receptor in modulating
      glutamatergic systems in the normal and diseased nervous system.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) play an important role in a
      variety of modulatory and regulatory processes including neurotransmitter release
      and synaptic transmission in various brain regions of the central nervous system
      (CNS). Glutamate is the principal excitatory neurotransmitter in the brain and
      the glutamatergic system participates in the pathophysiology of several
      neuropsychiatric disorders. Underpinning the importance of nAChRs, many studies
      demonstrated that nAChRs containing the alpha7 subunit facilitate glutamate
      release. Here, we review the currently available body of experimental evidence
      pertaining to alpha7 subunit containing nAChRs in their contribution to the
      modulation of glutamatergic neurotransmission, and we highlight the role of
      alpha7 in synaptic plasticity, the morphological and functional maturation of the
      glutamatergic system and therefore its important contribution in the modulation
      of neural circuits of the CNS. 

PMID- 26206185
TI  - Lessons learned from a novel calcium-channel protagonist and person.
AB  - A long time ago (circa 1976), David C. Triggle was Chair of the Department of
      Biochemical Pharmacology at S.U.N.Y. Buffalo where he led the faculty and staff
      in the education and mentoring of countless pharmacy and graduate students who
      passed through the hallowed halls of the University. Trained as a chemist, David
      spent his days synthesizing new and improved calcium channel blockers in a
      cramped, makeshift organic chemistry lab while a lab full of aspiring
      pharmacologists measured their effects on contractile responses of various smooth
      muscle preparations. I was a graduate student fortunate enough to land in David's
      laboratory, and thanks to him, I successfully navigated out with a Ph.D. in hand.
      That being said, his influence was less through his role as thesis advisor and
      more by the example he set in his simple, everyday life in Buffalo, N.Y: his love
      for - and dedication to - his family, his concern for the environment and his
      health, his perseverance in that tiny organic chemistry closet, his command of
      the English language, his unbridled honesty and cynicism, and his quiet pursuit
      of excellence. This article chronicles student life during that particular time
      period and provides a glimpse into David's unique personality and lifestyle that
      made him a role model to me and others. Interwoven is my own circuitous career
      path both before and after leaving S.U.N.Y. Buffalo that culminated in a
      productive career at the opposite end of the drug development process from where
      it all started in pharmacology. 

PMID- 26206186
TI  - New oleyl glycoside as anti-cancer agent that targets on neutral
      sphingomyelinase.
AB  - We designed and synthesized two anomeric oleyl glucosaminides as anti-cancer
      agents where the presence of a trifluoroacetyl group close to the anomeric center
      makes them resistant to hydrolysis by hexosaminidases. The oleyl glycosides share
      key structural features with synthetic and natural oleyl derivatives that have
      been reported to exhibit anti-cancer properties. While both glycosides showed
      antiproliferative activity on cancer cell lines, only the alpha-anomer caused
      endoplasmic reticulum (ER) stress and cell death on C6 glioma cells. Analysis of
      sphingolipids and glycosphingolipds in cells treated with the glycosides showed
      that the alpha-anomer caused a drastic accumulation of ceramide and
      glucosylceramide and reduction of lactosylceramide and GM3 ganglioside at
      concentrations above a threshold of 20 MUM. In order to understand how ceramide
      levels increase in response to alpha-glycoside treatment, further investigations
      were done using specific inhibitors of sphingolipid metabolic pathways. The
      pretreatment with 3-O-methylsphingomyelin (a neutral sphingomyelinase inhibitor)
      restored sphingomyelin levels together with the lactosylceramide and GM3
      ganglioside levels and prevented the ER stress and cell death caused by the alpha
      glycoside. The results indicated that the activation of neutral sphingomyelinase
      is the main cause of the alterations in sphingolipids that eventually lead to
      cell death. The new oleyl glycoside targets a key enzyme in sphingolipid
      metabolism with potential applications in cancer therapy.

PMID- 26206187
TI  - Concentration-response relationship of the alpha7 nicotinic acetylcholine
      receptor agonist FRM-17874 across multiple in vitro and in vivo assays.
AB  - Pharmacological activation of alpha7 nicotinic acetylcholine receptors (alpha7
      nAChRs) may improve cognition in schizophrenia and Alzheimer's disease. The
      present studies describe an integrated pharmacological analysis of the effects of
      FRM-17874, an analogue of encenicline, on alpha7 nAChRs in vitro and in
      behavioral and neurophysiological assays relevant to cognitive function. FRM
      17874 demonstrated high affinity binding to human alpha7 nAChRs, displacing
      [(3)H]-methyllacaconitine (Ki=4.3nM). In Xenopus laevis oocytes expressing human
      alpha7 nAChRs, FRM-17874 acted as an agonist, evoking inward currents with an
      EC50 of 0.42MUM. Lower concentrations of FRM-17874 (0.01-3nM) elicited no
      detectable current, but primed receptors to respond to sub-maximal concentrations
      of acetylcholine. FRM-17874 improved novel object recognition in rats, and
      enhanced memory acquisition and reversal learning in the mouse water T-maze.
      Neurophysiological correlates of cognitive effects of drug treatment, such as
      synaptic transmission, long-term potentiation, and hippocampal theta oscillation
      were also evaluated. Modulation of synaptic transmission and plasticity was
      observed in rat hippocampal slices at concentrations of 3.2 and 5nM. FRM-17874
      showed a dose-dependent facilitation of stimulation-induced hippocampal theta
      oscillation in mice and rats. The FRM-17874 unbound brain concentration-response
      relationship for increased theta oscillation power was similar in both species,
      exhibited a biphasic pattern peaking around 3nM, and overlapped with active doses
      and exposures observed in cognition assays. In summary, behavioral and
      neurophysiological assays indicate a bell-shaped effective concentration range
      and this report represents the first attempt to explain the concentration
      response function of alpha7 nAChR-mediated pro-cognitive effects in terms of
      receptor pharmacology. 

PMID- 26206189
TI  - Modulation of hippocampal neuronal network oscillations by alpha7 nACh receptors.
AB  - Synchronization of neuronal network oscillations within the cortex and
      hippocampus has been closely linked to various cognitive domains, including
      attention, learning, and memory. The frequency, power, and connectivity of
      hippocampal oscillations provide quantitative measures for examining the
      modulation of network activity, which influences mnemonic functions and memory
      formation. The wide distribution of alpha7 nicotinic acetylcholine receptors
      (alpha7 nAChRs) throughout the hippocampus makes them well positioned to modulate
      neuronal network activity. Elicitation of hippocampal theta through high
      frequency stimulation of the brainstem nucleus pontis oralis (nPO) is shown to be
      sensitive to several agents exhibiting pharmacological effects on cognition, thus
      representing a suitable preclinical screening assay for such drugs, including
      alpha7 nAChR agonists. We hypothesize that increases in theta power and theta
      phase gamma-amplitude coupling due to alpha7 nAChR agonists during elicited
      hippocampal oscillations could reflect changes in synchronous activity of
      pyramidal neurons which is a critical factor for hippocampal-dependent cognitive
      function. In this review, four major topics are discussed: neuronal network
      oscillations in the hippocampus, the characteristics and distribution of alpha7
      nAChRs therein, the modulation of elicited hippocampal theta and gamma
      oscillations by alpha7 nAChR agonists, as well as potential intrinsic roles of
      alpha7 nAChRs in hippocampal oscillations using alpha7 nAChR knock-out mice. 

PMID- 26206190
TI  - Dinner at Orazio's--David Triggle the model of a mentor.
AB  - What does it mean to be a mentor in science? Definitions of mentorship are freely
      spouted in publications and include concepts such as academic support,
      professional development, role modeling, interaction, impartment of knowledge,
      evaluation of work, demonstration of methodology, etc. Perhaps most of us would
      agree with the duties listed. But just what does it mean, for example, to offer
      academic support? How might one facilitate professional development for a mentee?
      While we may agree to the general obligations of a mentor the specifics of what
      these entail would prove more controversial. This article will illustrate how
      easy it is to pick out a bad mentor. There are certain elements of conduct that,
      if practiced, undoubtedly put you in the "bad mentor" category. However, it is
      very difficult to explain just what it means to be not only an adequate mentor
      but also a stellar one. It may be easy to list the roles and responsibilities of
      a mentor but just how should they be performed/carried out? David Triggle is the
      model of an extraordinary mentor. The conclusion of this paper will focus on some
      specific mentorship activities David Triggle carried out that illustrate some of
      the intangible aspects of excellence in mentorship. 

PMID- 26206188
TI  - Long-lasting changes in neural networks to compensate for altered nicotinic
      input.
AB  - The nervous system must balance excitatory and inhibitory input to constrain
      network activity levels within a proper dynamic range. This is a demanding
      requirement during development, when networks form and throughout adulthood as
      networks respond to constantly changing environments. Defects in the ability to
      sustain a proper balance of excitatory and inhibitory activity are characteristic
      of numerous neurological disorders such as schizophrenia, Alzheimer's disease,
      and autism. A variety of homeostatic mechanisms appear to be critical for
      balancing excitatory and inhibitory activity in a network. These are operative at
      the level of individual neurons, regulating their excitability by adjusting the
      numbers and types of ion channels, and at the level of synaptic connections,
      determining the relative numbers of excitatory versus inhibitory connections a
      neuron receives. Nicotinic cholinergic signaling is well positioned to contribute
      at both levels because it appears early in development, extends across much of
      the nervous system, and modulates transmission at many kinds of synapses.
      Further, it is known to influence the ratio of excitatory-to-inhibitory synapses
      formed on neurons during development. GABAergic inhibitory neurons are likely to
      be key for maintaining network homeostasis (limiting excitatory output), and
      nicotinic signaling is known to prominently regulate the activity of several
      GABAergic neuronal subtypes. But how nicotinic signaling achieves this and how
      networks may compensate for the loss of such input are important questions
      remaining unanswered. These issues are reviewed. 

PMID- 26206191
TI  - Activation of endplate nicotinic acetylcholine receptors by agonists.
AB  - The interaction of a small molecule made in one cell with a large receptor made
      in another is the signature event of cell signaling. Understanding the structure
      and energy changes associated with agonist activation is important for
      engineering drugs, receptors and synapses. The nicotinic acetylcholine receptor
      (AChR) is a ~300kD ion channel that binds the neurotransmitter acetylcholine
      (ACh) and other cholinergic agonists to elicit electrical responses in the
      central and peripheral nervous systems. This mini-review is in two sections.
      First, general concepts of skeletal muscle AChR operation are discussed in terms
      of energy landscapes for conformational change. Second, adult vs. fetal AChRs are
      compared with regard to interaction energies between ACh and agonist-site side
      chains, measured by single-channel electrophysiology and molecular dynamics
      simulations. The five aromatic residues that form the core of each agonist
      binding site can be divided into two working groups, a triad (led by alphaY190)
      that behaves similarly at all sites and a coupled pair (led by gammaW55) that has
      a large influence on affinity only in fetal AChRs. Each endplate AChR has 5
      homologous subunits, two of alpha(1) and one each of beta, delta, and either
      gamma (fetal) or epsilon (adult). These nicotinic AChRs have only 2 functional
      agonist binding sites located in the extracellular domain, at alphadelta and
      either alphagamma or alphaepsilon subunit interfaces. The receptor undergoes a
      reversible, global isomerization between structures called C and O. The C shape
      does not conduct ions and has a relatively low affinity for ACh, whereas O
      conducts cations and has a higher affinity. When both agonist sites are empty
      (filled only with water) the probability of taking on the O conformation (PO) is
      low, <10(-6). When ACh molecules occupy the agonist sites the C->O opening rate
      constant and C<->O gating equilibrium constant increase dramatically. Following a
      pulse of ACh at the nerve-muscle synapse, the endplate current rises rapidly to
      reach a peak that corresponds to PO ~0.96. 

PMID- 26206192
TI  - The Triggle effect.
AB  - Dr. David Triggle is considered a pioneer in the area of ion channel
      pharmacology. Over the course of his career, he made a number of particularly
      important contributions to our understanding of dihydropyridine interactions with
      L-type calcium channels. He also contributed his highly sought after expertise
      towards the drug discovery platform of the Canadian biopharmaceutical company,
      NeuroMed Pharmaceuticals (subsequently Zalicus). Here we briefly highlight his
      contributions to the field of calcium channel pharmacology, and then provide
      examples of his impact on NeuroMed. 

PMID- 26206193
TI  - Pro-oxidant activity of polyphenols and its implication on cancer chemoprevention
      and chemotherapy.
AB  - Reactive oxygen species (ROS) play a major role in carcinogenesis: pro-oxidant
      agents like tobacco smoke, asbestos or N-nitrosamines, are known as mutagenic and
      carcinogenic, and cancer cells show increased levels of ROS and redox
      deregulation. However, pro-oxidant molecules can also act as selective cytotoxic
      agents against cancer cells by achieving toxic levels of ROS. Although
      polyphenols are well-known as potent antioxidants, a pro-oxidant effect has been
      associated with their pro-apoptotic effect in various types of tumor cells. The
      aim of the present review is to present the main evidences of the pro-oxidant
      related cytotoxic activity of naturally occurring polyphenols and their
      underlying mechanisms. 

PMID- 26206196
TI  - Professionalism: An exemplar for the sciences.
AB  - The construct of a profession encompasses several core elements that guide the
      behavior of its members and the quality standards for the services they provide
      and products they produce: primarily, competency specifications for members of
      the profession, a code of professional and ethical behavior, and a commitment to
      serve the public good. Professionalism is the embodiment of a profession's
      expertise, ethos, and service to the public good. As an academic scientist, David
      Triggle exhibited an extraordinary mastery of professionalism in two domains:
      science and academic leadership in higher education. Sociocultural changes,
      including the commodification of knowledge, science, and higher education, are
      posing challenges to the professions and their traditional values. Whereas the
      effectiveness of ethics instruction is questionable, positive mentoring has shown
      promise as a means to help professionals maintain the ideals and the values of
      their chosen occupations. David Triggle was an extremely effective and revered
      mentor to numerous individuals in the sciences as well as in higher education,
      enhancing their professional enculturation and development. He fostered integrity
      of purpose in our respective professional lives and work, and was and remains an
      exemplar of professionalism. 

PMID- 26206194
TI  - Reducing inflammation and rescuing FTD-related behavioral deficits in progranulin
      deficient mice with alpha7 nicotinic acetylcholine receptor agonists.
AB  - Mutations in the progranulin gene cause frontotemporal dementia (FTD), a
      debilitating neurodegenerative disease that involves atrophy of the frontal and
      temporal lobes and affects personality, behavior, and language. Progranulin
      deficient mouse models of FTD exhibit deficits in compulsive and social behaviors
      reminiscent of patients with FTD, and develop excessive microgliosis and
      increased release of inflammatory cytokines. Activation of nicotinic
      acetylcholine receptors (nAChRs) by nicotine or specific alpha7 nAChR agonists
      reduces neuroinflammation. Here, we investigated whether activation of nAChRs by
      nicotine or alpha7 agonists improved the excessive inflammatory and behavioral
      phenotypes of a progranulin-deficient FTD mouse model. We found that treatment
      with selective alpha7 agonists, PHA-568487 or ABT-107, strongly suppressed the
      activation of NF-kappaB in progranulin-deficient cells. Treatment with ABT-107
      also reduced microgliosis, decreased TNFalpha levels, and reduced compulsive
      behavior in progranulin-deficient mice. Collectively, these data suggest that
      targeting activation of the alpha7 nAChR pathway may be beneficial in decreasing
      neuroinflammation and reversing some of the behavioral deficits observed in
      progranulin-deficient FTD. 

PMID- 26206195
TI  - Berberine induces GLP-1 secretion through activation of bitter taste receptor
      pathways.
AB  - Our previous studies revealed that berberine-mediated GLP-1 secretion was a
      possible mechanism for berberine exerting good effects on hyperglycemia. This
      study was designed to ascertain whether berberine-induced secretion of GLP-1 was
      related with activation of bitter taste receptors expressed in gastrointestinal
      tract. Western blotting results showed that TAS2R38, a subtype of bitter taste
      receptor, was expressed on human enteroendocrine NCI-H716 cells. GLP-1 secretion
      induced by berberine from NCI-H716 cells was inhibited by incubation with anti
      TAS2R38 antibody. We further performed gene silencing using siRNA to knockdown
      TAS2R38 from NCI-H716 cells, which showed that siRNA knockdown of the TAS2R38
      reduced berberine-mediated GLP-1 secretion. We adopted inhibitors of PLC and
      TRPM5 known to be involved in bitter taste transduction to investigate the
      underlying pathways mediated in berberine-induced GLP-1 secretion. It was found
      that PLC inhibitor U73122 inhibited berberine-induced GLP-1 release in NCI-H716
      cells, while TRPM5 blocker quinine failed to attenuate berberine-induced
      secretion of GLP-1. The present results demonstrated that berberine stimulated
      GLP-1 secretion via activation of gut-expressed bitter taste receptors in a PLC
      dependent manner. Because berberine was found to be a ligand of bitter taste
      receptor, the results of present study may provide an explanation for some bitter
      taste substance obtain hypoglycemic effect. 

PMID- 26206197
TI  - David J. Triggle: Medicinal chemistry, to pharmacology, calcium channels, and
      beyond.
AB  - David Triggle's scientific career began as a chemist, went through medicinal
      chemistry into pharmacology, and finally on to somewhat more philosophical
      interests in later years. It was a career marked by many contributions to all of
      those aspects of science. Chief amongst his many contributions, in addition to
      those in medicinal chemistry, was his work on the drugs known as calcium ion
      channel blockers or (calcium antagonists). In the calcium ion channel field he
      was a particularly instrumental figure in sorting out the mechanisms, actions and
      roles of the class of calcium channel blockers, known chemical and
      pharmacologically as the dihydropyridines (DHPs) in particular, as well as other
      calcium blockers of diverse structures. During the course of a long career, and
      extensive journeys into medicinal chemistry and pharmacology, he published
      voluminously in terms of papers, reviews, conference proceedings and books.
      Notably, many of his papers often had limited authorship where, as senior author
      it reflected his deep involvement in all aspects of the reported work. His work
      always helped clarify the field while his incisive reviews, together with his
      role in coordinating and running scientific meetings, were a great help in
      clarifying and organizing various fields of study. He has had a long and
      illustrious career, and is wellknown in the world of biomedical science; his
      contributions are appreciated, and well recognized everywhere. The following
      article attempts to chart a path through his work and contributions to medicinal
      chemistry, pharmacology, science, academia and students. 

PMID- 26206198
TI  - Inhibition of hedgehog signaling reduces the side population in human malignant
      mesothelioma cell lines.
AB  - Deregulation of crucial embryonic pathways, including hedgehog signaling, has
      been frequently implicated in a variety of human cancers and is emerging as an
      important target for anticancer therapy. This study evaluated the potential
      anticancer effects of cyclopamine, a chemical inhibitor of hedgehog signaling, in
      human malignant mesothelioma (HMM) cell lines. Cyclopamine treatment
      significantly decreased the proliferation of HMM cells by promoting apoptosis and
      shifting the cell cycle toward dormant phase. The clonogenicity and mobility of
      HMM cells were significantly decreased by cyclopamine treatment. Treatment of HMM
      cells with cyclopamine significantly reduced the abundance of side population
      cells, which were measured using an assay composed of Hoechst 33342 dye staining
      and subsequent flow cytometry. Furthermore, the expression levels of stemness
      related genes were significantly affected by cyclopamine treatment. Taken
      together, the present study showed that targeting hedgehog signaling could reduce
      a more aggressive subpopulation of the cancer cells, suggesting an alternative
      approach for HMM therapy.

PMID- 26206199
TI  - The influence of habitat fragmentation on helminth communities in rodent
      populations from a Brazilian Mountain Atlantic Forest.
AB  - The influence of habitat structure on helminth communities of three sigomdontinae
      rodent species (Akodon cursor, A. montensis and Oligoryzomys nigripes) was
      investigated in forest fragments within an agricultural landscape in south
      eastern Brazil. This is a pionner study correlating the occurrence of helminth
      species of rodent hosts with microhabitat characteristics. Rodents were collected
      from 12 fragments and in a continuous conserved area. Up to 13 nematode, three
      cestode and two trematode species were identified, and habitat fragmentation was
      found to have more influence on the helminth composition of O. nigripes compared
      to the other two rodent species. Fragmentation appeared to limit the development
      of some helminths' life cycles, e.g. with some species such as Trichofreitasia
      lenti, Protospirura numidica, Cysticercus fasciolaris and Avellaria sp.,
      occurring mostly in areas with less anthropic impact. However, fragmentation did
      not seem to affect the life cycles of other dominant helminths, such as the
      trematode Canaania obesa, the nematodes Stilestrongylus lanfrediae, S. eta and S.
      aculeata, and the cestode Rodentolepis akodontis. The helminth community
      structure followed a nested pattern of distribution in A. montensis and O.
      nigripes. Stilestrongylus lanfrediae seemed to be more associated with dense
      understorey, C. obesa with open canopy and dense understorey, and
      Guerrerostrongylus zetta with organic matter on the ground. Their presence in
      each area may be explained by aspects of their life cycles that take place in the
      external environment outside the host. 

PMID- 26206200
TI  - Prediction of Intrinsic Cesium Desorption from Na-Smectite in Mixed Cation
      Solutions.
AB  - Quantitative understanding of the stability of sorbed radionuclides in smectite
      is necessary to assess the performance of engineering barriers used for nuclear
      waste disposal. Our previous study demonstrated that the spatial organization of
      the smectite platelets triggered by the divalent cations led to the apparent
      fixation of intrinsic Cs in smectite, because some Cs is retained inside the
      formed tactoids. Natural water is usually a mixture of Na(+) and divalent cations
      (Ca(2+) and Mg(2+)). This study therefore investigated the desorption behavior of
      intrinsic Cs in Na-smecite in mixed Na(+)-divalent cation solutions under widely
      various cation concentrations using batch experiments, grain size measurements,
      and cation exchange modeling (CEM). Results show that increased Na(+)
      concentrations facilitate Cs desorption because Na(+) serves as the dispersion
      agent. A linear relation was obtained between the logarithm of the Na(+) fraction
      and the accessible Cs fraction in smectite. That relation enables the prediction
      of accessible Cs fraction as a function of solution cationic compositions. The
      corrected CEM considering the effects of the spatial organization suggests that
      the stability of intrinsic Cs in the smectite is governed by the Na(+)
      concentration, and suggests that it is almost independent of the concentrations
      of divalent cations in natural water. 

PMID- 26206201
TI  - The Association of Specific Executive Functions and Falls Risk in People with
      Mild Cognitive Impairment and Early-Stage Dementia.
AB  - BACKGROUND/AIMS: Impairment in executive function is associated with a heightened
      risk for falls in people with mild cognitive impairment (MCI) and dementia. The
      purpose of this study was to determine which aspects of executive function are
      associated with falls risk. METHODS: Forty-two participants with a mean age of
      81.6 years and a diagnosis of MCI or mild dementia completed five different
      executive function tests from the computerised CANTAB test battery and a
      comprehensive falls risk assessment. RESULTS: A hierarchical regression analysis
      showed that falls risk was significantly associated with spatial memory abilities
      and inhibition of a pre-potent response. CONCLUSION: The concept of executive
      function may be too general to provide meaningful results in a research or
      clinical context, which should focus on spatial memory and inhibition of a pre
      potent response.

PMID- 26206202
TI  - Intranasal delivery: circumventing the iron curtain to treat neurological
      disorders.
AB  - INTRODUCTION: The blood-brain barrier (BBB) is like an iron curtain that prevents
      exogenous substances, including most drugs, from entering the CNS. Intranasal
      delivery has been demonstrated to circumvent the BBB due to the special anatomy
      of the olfactory and trigeminal neural pathways that connect the nasal mucosa
      with the brain and the perivascular pathway within the CNS. In the last two
      decades, the concepts, mechanisms and pathways of intranasal delivery to the CNS
      have led to great success both in preclinical and clinical studies. More
      researchers have translated results from bench to bedside, and a number of
      publications have reported the clinical application of intranasal delivery. AREAS
      COVERED: This review summarizes results from recent clinical trials utilizing
      intranasal delivery of therapeutics to explore its pharmacokinetics and
      application to treating neurological disorders. Moreover, existing problems with
      the methods and possible solutions have also been discussed. The promising
      results from clinical trials have demonstrated that intranasal delivery provides
      an extraordinary approach for circumventing the BBB. Many drugs, including high
      molecular-weight molecules, could potentially improve the treatment of
      neurological disorders via intranasal administration. EXPERT OPINION: Intranasal
      delivery is a novel method with great potential for delivering and targeting
      therapeutics to the CNS to treat neurological disorders.

PMID- 26206203
TI  - Tsunami inundation after the Great East Japan Earthquake and mortality of
      affected communities.
AB  - OBJECTIVE: To examine the relationship between mortality rate and tsunami
      inundation after the Great East Japan Earthquake (GEJE) in 2011. STUDY DESIGN:
      Cross-sectional study. METHODS: One hundred and fifty-five town or village
      sections in Ishinomaki, Myagi Prefecture, were included in this study. Three
      areas in the city were classified by characteristic landforms: plains area (n =
      114), ria coastal area (n = 27) and Kitakami riverside (n = 14). The correlation
      coefficient between tsunami inundation depth and mortality rate was calculated
      for each area, and the differences between the areas were examined. Furthermore,
      multivariate analyses adjusted for the characteristics of the sections were
      conducted using census data taken before the GEJE. RESULTS: An association was
      found between inundation depth and mortality rate for Ishinomaki as a whole (r =
      0.65, P < 0.001), Kitakami riverside (r = 0.85, P < 0.001) and the plains area (r
      = 0.75, P < 0.001) in separate analyses. However, no association was detected
      between inundation depth and mortality rate for the ria coastal area (r = 0.14, P
      = 0.47). CONCLUSION: The ria coastal area has good accessibility to the hills and
      tight bonding between members of the community. These factors seemed to play
      crucial roles in the lower mortality rate in this area despite the deep
      inundation.

PMID- 26206205
TI  - Editorial: Image-Guided Drug Delivery: State of the Art.

PMID- 26206204
TI  - On the Modulation of Brain Activation During Simulated Weight Bearing in Supine
      Gait-Like Stepping.
AB  - To date, the neurophysiological correlates of muscle activation required for
      weight bearing during walking are poorly understood although, a supraspinal
      involvement has been discussed in the literature for many years. The present
      study investigates the effect of simulated ground reaction forces (0, 20, and 40%
      of individual body weight) on brain activation in sixteen healthy participants. A
      magnetic resonance compatible robot was applied to render three different levels
      of load against the feet of the participants during active and passive gait-like
      stepping movements. Brain activation was analyzed by the means of voxel-wise
      whole brain analysis as well as by a region-of-interest analysis. A significant
      modulation of brain activation in sensorimotor areas by the load level could
      neither be demonstrated during active nor during passive stepping. These
      observations suggest that the regulation of muscle activation under different
      weight-bearing conditions during stepping occurs at the level of spinal circuitry
      or the brainstem rather than at the supraspinal level.

PMID- 26206206
TI  - Probing the role of highly conserved residues in triosephosphate isomerase-
      analysis of site specific mutants at positions 64 and 75 in the Plasmodial
      enzyme.
AB  - Highly conserved residues in enzymes are often found to be clustered close to
      active sites, suggesting that functional constraints dictate the nature of amino
      acid residues accommodated at these sites. Using the Plasmodium falciparum
      triosephosphate isomerase (PfTIM) enzyme (EC 5.3.1.1) as a template, we have
      examined the effects of mutations at positions 64 and 75, which are not directly
      involved in the proton transfer cycle. Thr (T) occurring at position 75 is
      completely conserved, whereas only Gln (Q) and Glu (E) are accommodated at
      position 64. Biophysical and kinetic data are reported for four T75 (T75S/V/C/N)
      and two Q64 (Q64N/E) mutants. The dimeric structure is weakened in the Q64E and
      Q64N mutants, whereas dimer integrity is unimpaired in all four T75 mutants.
      Measurement of the concentration dependence of enzyme activity permits an
      estimate of Kd values for dimer dissociation (Q64N = 73.7 +/- 9.2 nm and Q64E =
      44.6 +/- 8.4 nm). The T75S/V/C mutants have activities comparable to the wild
      type enzyme, whereas a fourfold drop is observed for T75N. All four T75 mutants
      show a dramatic fall in activity between 35  degrees C and 45  degrees C. Crystal
      structure determination of the T75S/V/N mutants provides insights into the
      variations in local interactions, with the T75N mutant showing the largest
      changes. Hydrogen-bond interactions determine dimer stability restricting the
      choice of residues at position 64 to Gln (Q) and Glu (E). At position 75, the
      overwhelming preference for Thr (T) may be dictated by the imperative of
      maintaining temperature stability of enzyme activity. DATABASE: Structural data
      have been deposited in the Protein Data Bank under accession numbers 4ZZ9, 5BMW,
      5BMX, 5BNK and 5BRB.

PMID- 26206207
TI  - Response to 'Re: Endovascular Treatment of Ruptured Abdominal Aortic Aneurysms
      with Hostile Aortic Neck Anatomy'.

PMID- 26206208
TI  - Commentary on 'Adjustable Velcro Compression Devices are More Effective than
      Inelastic Bandages in Reducing Venous Edema in the Initial Treatment Phase: A
      Randomized Controlled Trial'.

PMID- 26206209
TI  - The PPARbeta/delta Agonist GW0742 Induces Early Neuronal Maturation of Cortical
      Post-Mitotic Neurons: Role of PPARbeta/delta in Neuronal Maturation.
AB  - Increasing evidences support that signaling lipids participate in synaptic
      plasticity and cell survival, and that the lipid signaling is closely associated
      with neuronal differentiation, learning, and memory and with pathologic events,
      such as epilepsy and Alzheimer's disease. The Peroxisome Proliferator-Activated
      Receptors (PPAR) are strongly involved in the fatty acid cell signaling, as many
      of the natural lypophylic compounds are PPAR ligands. We have previously shown
      that PPARbeta/delta is the main isotype present in cortical neuron primary
      cultures and that during neuronal maturation, PPARbeta/delta is gradually
      increased and activated. To get more insight into the molecular mechanism by
      which PPARbeta/delta may be involved in neuronal maturation processes, in this
      work a specific PPARbeta/delta agonist, GW0742 was used administered alone or in
      association with a specific PPARbeta/delta antagonist, the GSK0660, and the
      parameters involved in neuronal differentiation and maturation were assayed. The
      data obtained demonstrated the strong involvement of PPARbeta/delta in neuronal
      maturation, triggering the agonist an anticipation of neuronal differentiation,
      and the antagonist abolishing the observed effects. These effects appear to be
      mediated by the activation of BDNF pathway.

PMID- 26206210
TI  - Is substantial renal dysfunction in patients with heart failure no longer a
      contraindication for RAS inhibition? The power of a large, high-quality registry
      to illuminate major clinical issues.

PMID- 26206212
TI  - Requiem for the 'vulnerable plaque'.

PMID- 26206211
TI  - The microRNA-221/-222 cluster balances the antiviral and inflammatory response in
      viral myocarditis.
AB  - AIMS: Viral myocarditis (VM) is an important cause of heart failure and sudden
      cardiac death in young healthy adults; it is also an aetiological precursor of
      dilated cardiomyopathy. We explored the role of the miR-221/-222 family that is
      up-regulated in VM. METHODS AND RESULTS: Here, we show that microRNA-221 (miR
      221) and miR-222 levels are significantly elevated during acute VM caused by
      Coxsackievirus B3 (CVB3). Both miRs are expressed by different cardiac cells and
      by infiltrating inflammatory cells, but their up-regulation upon myocarditis is
      mostly exclusive for the cardiomyocyte. Systemic inhibition of miR-221/-222 in
      mice increased cardiac viral load, prolonged the viraemic state, and strongly
      aggravated cardiac injury and inflammation. Similarly, in vitro, overexpression
      of miR-221 and miR-222 inhibited enteroviral replication, whereas knockdown of
      this miR-cluster augmented viral replication. We identified and confirmed a
      number of miR-221/-222 targets that co-orchestrate the increased viral
      replication and inflammation, including ETS1/2, IRF2, BCL2L11, TOX, BMF, and
      CXCL12. In vitro inhibition of IRF2, TOX, or CXCL12 in cardiomyocytes
      significantly dampened their inflammatory response to CVB3 infection, confirming
      the functionality of these targets in VM and highlighting the importance of miR
      221/-222 as regulators of the cardiac response to VM. CONCLUSIONS: The miR-221/
      222 cluster orchestrates the antiviral and inflammatory immune response to viral
      infection of the heart. Its inhibition increases viral load, inflammation, and
      overall cardiac injury upon VM.

PMID- 26206213
TI  - Danon disease: a rare cause of left ventricular hypertrophy with cardiac magnetic
      resonance follow-up.

PMID- 26206214
TI  - Prosthetic aortic valve endocarditis with pseudoaneurysm complicated by
      additional rupture of mitral-aortic intervalvular fibrosa.

PMID- 26206215
TI  - Intrinsic magnetic properties of bimetallic nanoparticles elaborated by cluster
      beam deposition.
AB  - In this paper, we present some specific chemical and magnetic order obtained very
      recently on characteristic bimetallic nanoalloys prepared by mass-selected Low
      Energy Cluster Beam Deposition (LECBD). We study how the competition between d
      atom hybridization, complex structure, morphology and chemical affinity affects
      their intrinsic magnetic properties at the nanoscale. The structural and magnetic
      properties of these nanoalloys were investigated using various experimental
      techniques that include High Resolution Transmission Electron Microscopy (HRTEM),
      Superconducting Quantum Interference Device (SQUID) magnetometry, as well as
      synchrotron techniques such as Extended X-ray Absorption Fine Structure (EXAFS)
      and X-ray Magnetic Circular Dichroism (XMCD). Depending on the chemical nature of
      the nanoalloys we observe different magnetic responses compared to their bulk
      counterparts. In particular, we show how specific relaxation in nanoalloys
      impacts their magnetic anisotropy; and how finite size effects (size reduction)
      inversely enhance their magnetic moment. 

PMID- 26206216
TI  - Early Incorporation of an Evidence-Based Aquatic-Assisted Approach to
      Arthroscopic Rotator Cuff Repair Rehabilitation: Prospective Case Study.
AB  - BACKGROUND AND PURPOSE: Both traditional and progressive rotator cuff repair
      rehabilitation protocols often delay active motion of the shoulder for 6 weeks or
      more. The early inclusion of a comprehensive aquatic-assisted exercise program
      presents a unique approach to postoperative management. The purpose of this case
      study is to describe a comprehensive evidence-based, aquatic-assisted
      rehabilitation program following arthroscopic rotator cuff repair. CASE
      DESCRIPTION: A 73-year-old woman with a nonretracted, medium-size, full-thickness
      tear (2.5 cm) of the supraspinatus tendon underwent arthroscopic rotator cuff
      repair and was referred for postoperative physical therapy. The rehabilitation
      program was initiated at 2 weeks postoperatively and consisted of concurrent land
      and aquatic-based interventions over 6 weeks for a total of 18 physical therapy
      visits. OUTCOMES: Improvements were made in all 5 patient-reported outcome
      measures that were recorded weekly over the course of care. Improvements reached
      or exceeded minimal detectable change levels for the Shoulder Pain and Disability
      Index and the Penn Shoulder Score. Her numeric pain rating scale score at rest
      decreased from 4/10 at the initial evaluation to 2/10 at 8 weeks postoperatively
      and with activity decreased from 9/10 to 6/10. Shoulder strength and range of
      motion values also exhibited improvement over the course of care. No adverse
      events occurred during the case study. DISCUSSION: This case study illustrates
      the safe inclusion of low-stress aquatic exercises as an early adjunct to
      traditional land-based rotator cuff repair rehabilitation programs in small- to
      medium-size repairs. Further studies are needed to determine the long-term
      effectiveness of adding aquatic therapy to traditional postoperative programs.

PMID- 26206217
TI  - "You Have to Keep Moving, Be Active": Perceptions and Experiences of Habitual
      Physical Activity in Older Women With Osteoporosis.
AB  - BACKGROUND: Physical activity (PA) is essential for older adults with
      osteoporosis, and health care professionals play important roles in promoting PA
      and encouraging patients to make healthy choices. However, many factors influence
      habitual PA, and there is only limited knowledge about the perceptions and
      experiences of PA among older women with osteoporosis. OBJECTIVES: The purpose of
      this study was to describe perceptions and experiences of PA and the factors that
      influence habitual PA among older adults with osteoporosis, impaired balance, and
      fear of falling. DESIGN: This was a qualitative interview study applying
      interpretive content analysis with an inductive approach. METHODS: Informants
      were a purposeful sample of 18 women, aged 66 to 86 years, with osteoporosis,
      impaired balance, and fear of falling. Individual, semistructured, face-to-face
      interviews were recorded, transcribed, condensed, and coded to find subthemes and
      themes. RESULTS: The overall theme found was "Physical activity--a tool for
      staying healthy with osteoporosis." This overall theme comprised 2 main themes
      interpreting the challenges and possibilities of being physically active with
      osteoporosis. These themes were not separate but rather linked to each other like
      2 sides of the same coin, with factors that could act as both barriers to and
      facilitators of PA. Personal preferences and osteoporosis-related concerns
      influenced habitual PA, and individualization was perceived as important.
      LIMITATIONS: Some results may be context specific and limit the transferability
      to people with other cultural or socioeconomic backgrounds. CONCLUSIONS: The
      women perceived that PA was an important tool to maintain health with
      osteoporosis and believed that they had a responsibility to use this tool. They
      had adapted to disease-specific limitations and developed strategies to overcome
      challenges and barriers to PA. Lack of PA promotion and conflicting advice about
      PA from physicians created uncertainty. Encouragement and guidance from physical
      therapists, individually or in groups, were very important.

PMID- 26206218
TI  - Personal Perspectives on Enablers and Barriers to Accessing Care for Hip and Knee
      Osteoarthritis.
AB  - BACKGROUND: Despite increasing demand for joint replacement surgery and other
      health services for hip and knee osteoarthritis (OA), barriers and enablers to
      individual access to care are not well understood. A comprehensive understanding
      of drivers at all levels is needed to inform efforts for improving access.
      OBJECTIVE: The aim of this study was to explore perceived barriers and enablers
      to receiving conservative (nonsurgical) and surgical treatment for hip and knee
      OA. DESIGN: This was a qualitative study using directed content analysis.
      METHODS: Semistructured telephone interviews were conducted, with 33 participants
      randomly sampled from an Australian population-based survey of hip and knee OA.
      Each interview covered factors contributing to receiving treatment for OA and
      perceived barriers to accessing care. Interview transcripts were coded and
      organized into themes. RESULTS: Key barriers to accessing care for OA included
      medical opinions about saving surgery for later and the appropriate age for joint
      replacement. Other common barriers included difficulty obtaining referrals or
      appointments, long waiting times, work-related issues, and limited availability
      of primary and specialist care in some areas. Several participants perceived a
      lack of effective treatment for OA. Private health insurance was the most
      frequently cited enabler and was perceived to support the costs of surgical and
      conservative treatments, including physical therapy, while facilitating faster
      access to surgery. Close proximity to services and assistance from medical
      professionals in arranging care also were considered enablers. CONCLUSIONS:
      People with hip or knee OA experience substantial challenges in accessing
      treatment, and these challenges relate predominantly to health professionals,
      health systems, and financial factors. Private health insurance was the strongest
      perceived enabler to accessing care for OA.

PMID- 26206219
TI  - 46th Mary McMillan Lecture: Not Eureka.

PMID- 26206220
TI  - Reactive Balance in Individuals With Chronic Stroke: Biomechanical Factors
      Related to Perturbation-Induced Backward Falling.
AB  - BACKGROUND: An effective compensatory stepping response is the first line of
      defense for preventing a fall during sudden large external perturbations. The
      biomechanical factors that contribute to heightened fall risk in survivors of
      stroke, however, are not clearly understood. It is known that impending
      sensorimotor and balance deficits poststroke predispose these individuals to a
      risk of fall during sudden external perturbations. OBJECTIVE: The purpose of this
      study was to examine the mechanism of fall risk in survivors of chronic stroke
      when exposed to sudden, slip-like forward perturbations in stance. DESIGN: This
      was a cross-sectional study. METHODS: Fourteen individuals with stroke, 14 age
      matched controls (AC group), and 14 young controls (YC group) were exposed to
      large-magnitude forward stance perturbations. Postural stability was computed as
      center of mass (COM) position (XCOM/BOS) and velocity (XCOM/BOS) relative to the
      base of support (BOS) at first step lift-off (LO) and touch-down (TD) and at
      second step TD. Limb support was quantified as vertical hip descent (Zhip) from
      baseline after perturbation onset. RESULTS: All participants showed a backward
      balance loss, with 71% of the stroke group experiencing a fall compared with no
      falls in the control groups (AC and YC groups). At first step LO, no between
      group differences in XCOM/BOS and XCOM/BOS were noted. At first step TD, however,
      the stroke group had a significantly posterior XCOM/BOS and backward XCOM/BOS
      compared with the control groups. At second step TD, individuals with stroke were
      still more unstable (more posterior XCOM/BOS and backward XCOM/BOS) compared with
      the AC group. Individuals with stroke also showed greater peak Zhip compared with
      the control groups. Furthermore, the stroke group took a larger number of steps
      with shorter step length and delayed step initiation compared with the control
      groups. LIMITATIONS: Although the study highlights the reactive balance deficits
      increasing fall risk in survivors of stroke compared with healthy adults, the
      study was restricted to individuals with chronic stroke only. It is likely that
      comparing compensatory stepping responses across different stages of recovery
      would enable clinicians to identify reactive balance deficits related to a
      specific stage of recovery. CONCLUSIONS: These findings suggest the inability of
      the survivors of stroke to regain postural stability with one or more
      compensatory steps, unlike their healthy counterparts. Such a response may expose
      them to a greater fall risk resulting from inefficient compensatory stepping and
      reduced vertical limb support. Therapeutic interventions for fall prevention,
      therefore, should focus on improving both reactive stepping and limb support.

PMID- 26206227
TI  - Management of hyperosmolar hyperglycaemic state in adults with diabetes.

PMID- 26206226
TI  - Attenuation of inflammatory response by a novel chalcone protects kidney and
      heart from hyperglycemia-induced injuries in type 1 diabetic mice.
AB  - High glucose-induced inflammatory response in diabetic complications plays an
      important role in disease occurrence and development. With inflammatory cytokines
      and signaling pathways as important mediators, targeting inflammation may be a
      new avenue for treating diabetic complications. Chalcones are a class of natural
      products with various pharmacological activities. Previously, we identified L2H17
      as a chalcone with good anti-inflammatory activity, inhibiting LPS-induced
      inflammatory response in macrophages. In this study, we examined L2H17's effect
      on hyperglycemia-induced inflammation both in mouse peritoneal macrophages and a
      streptozotocin-induced T1D mouse model. Our results indicate that L2H17 exhibits
      a strong inhibitory effect on the expression of pro-inflammatory cytokines, cell
      adhesion molecules, chemokines and macrophage adhesion via modulation of the
      MAPK/NF-kappaB pathway. Furthermore, in vivo oral administration of L2H17
      resulted in a significant decrease in the expression of pro-inflammatory
      cytokines and cell adhesion molecules, contributing to a reduction of key markers
      for renal and cardiac dysfunction and improvements in fibrosis and pathological
      changes in both renal and cardiac tissues of diabetic mice. These findings
      provide the evidence supporting targeting MAPK/NF-kappaB pathway may be effective
      therapeutic strategy for diabetic complications, and suggest that L2H17 may be a
      promising anti-inflammatory agent with potential as a therapeutic agent in the
      treatment of renal and cardiac diabetic complications. 

PMID- 26206228
TI  - Asp3Gly polymorphism affects fatty acid-binding protein 3 intracellular stability
      and subcellular localization.
AB  - Fatty acid-binding proteins (FABP) play a crucial role in intracellular fatty
      acid transportation and metabolism. In this study, we investigate the effects of
      the FABP3 Asp3Gly (D3G) polymorphism on protein structure and function. Although
      the mutation did not alter protein secondary structure or the ability to bind 1
      anilinonaphthalene-8-sulfonic acid and palmitate, the intracellular stability of
      the D3G mutant was significantly decreased. Immunocytochemical analysis reveals
      that the mutation alters FABP3 subcellular localization. Our results suggest that
      the D3G polymorphism may impact energy metabolism and physiological functions. 

PMID- 26206229
TI  - The iPLA(2)gamma is identified as the membrane potential sensitive phospholipase
      in liver mitochondria.
AB  - Previous reports from our lab identified a mitochondrial calcium-independent
      phospholipase A2 activity that is activated when the mitochondrial membrane
      potential is decreased. This activity was demonstrated to influence occurrence of
      the permeability transition. Originally, this activity was ascribed to the
      iPLA2beta protein. Recently, both iPLA2beta and iPLA2gamma knock out mice have
      been generated. It has been shown by others that the iPLA2gamma plays a
      significant role in progression of the permeability transition. In this paper,
      using the iPLA2beta and iPLA2gamma knock out mice we show that the membrane
      potential sensitive activity is the iPLA2gamma. 

PMID- 26206230
TI  - Cannabinoids for the Treatment of Movement Disorders.
AB  - OPINION STATEMENT: Use of cannabinoids as medications has a long history.
      Unfortunately, the prohibition of cannabis and its classification in 1970 as a
      schedule 1 drug has been a major obstacle in studying these agents in a
      systematic, controlled manner. The number of class 1 studies (randomized, double
      blind, placebo-controlled) in patients with movement disorders is limited. Hence,
      it is not possible to make recommendations on the use of these cannabinoids as
      primary treatments for any of the movement disorders at this time. Fortunately,
      there is an expanding body of research in animal models of age-dependent and
      disease-related changes in the endocannabinoid system that is providing new
      targets for drug development. Moreover, there is growing evidence of a
      "cannabinoid entourage effect" in which a combination of cannabinoids derived
      from the plant are more effective than any single cannabinoid for a number of
      conditions. Cannabis preparations may presently offer an option for compassionate
      use in severe neurologic diseases, but at this point, only when standard-of-care
      therapy is ineffective. As more high-quality clinical data are gathered, the
      therapeutic application of cannabinoids will expand.

PMID- 26206231
TI  - Violations of Personal Space in Young People with Autism Spectrum Disorders and
      Williams Syndrome: Insights from the Social Responsiveness Scale.
AB  - Interpersonal distance regulation is crucial for successful social interactions.
      We investigated personal space awareness in Williams syndrome (WS) and autism
      spectrum disorder (ASD) compared to typical development. Parents reported that
      individuals with WS and ASD were significantly more likely than those developing
      typically to invade the personal space of others. WS individuals were reported to
      have the least awareness of the personal space boundaries of others. Despite the
      suggested opposing social profiles of WS and ASD, some similarities are present
      in the ability, or indeed inability, to regulate interpersonal distance during
      social interactions. Findings are discussed in relation to implications of
      atypical amygdala function, inhibitory control and anxiety on real-world
      behaviour for such socially vulnerable groups. 

PMID- 26206232
TI  - Network approach to autistic traits: group and subgroup analyses of ADOS item
      scores.
AB  - A network conceptualization might contribute to understanding the occurrence and
      interacting nature of behavioral traits in the autism realm. Networks were
      constructed based on correlations of item scores of the Autism Diagnostic
      Observation Schedule for Modules 1, 2 and 3 obtained for a group of 477 Dutch
      individuals with developmental disorders. After combining Modules, networks were
      obtained and compared for male versus female, high- versus low-functioning,
      seizure versus non-seizure, autism spectrum disorder versus intellectual
      disability, and younger versus older subjects. The network visualizations and
      calculated network parameters provide new perspectives that generate new
      hypothesis and suggest follow-up studies. The approach should be useful in
      characterizing individuals and groups, in elucidating mechanisms of trait
      generation and routes to outcome phenotypes, and in suggesting points of
      intervention. 

PMID- 26206233
TI  - A transcriptome-wide study on the microRNA- and the Argonaute 1-enriched small
      RNA-mediated regulatory networks involved in plant leaf senescence.
AB  - Leaf senescence is an important physiological process during the plant life
      cycle. However, systemic studies on the impact of microRNAs (miRNAs) on the
      expression of senescence-associated genes (SAGs) are lacking. Besides, whether
      other Argonaute 1 (AGO1)-enriched small RNAs (sRNAs) play regulatory roles in
      leaf senescence remains unclear. In this study, a total of 5,123 and 1,399 AGO1
      enriched sRNAs, excluding miRNAs, were identified in Arabidopsis thaliana and
      rice (Oryza sativa), respectively. After retrieving SAGs from the Leaf Senescence
      Database, all of the AGO1-enriched sRNAs and the miRBase-registered miRNAs of
      these two plants were included for target identification. Supported by degradome
      signatures, 200 regulatory pairs involving 120 AGO1-enriched sRNAs and 40 SAGs,
      and 266 regulatory pairs involving 64 miRNAs and 42 SAGs were discovered in
      Arabidopsis. Moreover, 13 genes predicted to interact with some of the above
      identified target genes at protein level were validated as regulated by 17 AGO1
      enriched sRNAs and ten miRNAs in Arabidopsis. In rice, only one SAG was targeted
      by three AGO1-enriched sRNAs, and one SAG was targeted by miR395. However, five
      AGO1-enriched sRNAs were conserved between Arabidopsis and rice. Target genes
      conserved between the two plants were identified for three of the above five
      sRNAs, pointing to the conserved roles of these regulatory pairs in leaf
      senescence or other developmental procedures. Novel targets were discovered for
      three of the five AGO1-enriched sRNAs in rice, indicating species-specific
      functions of these sRNA-target pairs. These results could advance our
      understanding of the sRNA-involved molecular processes modulating leaf
      senescence. 

PMID- 26206234
TI  - Detection of a novel variant of HLA-A*02, HLA-A*02:570, in a Taiwanese unrelated
      hematopoietic stem cell donor.
AB  - Two nucleotide changes at residue 142 (G -> A) and residue 144 (A -> C) of HLA
      A*02:01:01:01 result in a novel allele, HLA-A*02:570. 

PMID- 26206237
TI  - Reply.

PMID- 26206235
TI  - Usefulness of targeting lymphocyte Kv1.3-channels in the treatment of respiratory
      diseases.
AB  - T lymphocytes predominantly express delayed rectifier K(+)-channels (Kv1.3) in
      their plasma membranes. Patch-clamp studies revealed that the channels play
      crucial roles in facilitating the calcium influx necessary to trigger lymphocyte
      activation and proliferation. Using selective channel inhibitors in experimental
      animal models, in vivo studies further revealed the clinically relevant
      relationship between the channel expression and the development of chronic
      respiratory diseases, in which chronic inflammation or the overstimulation of
      cellular immunity in the airways is responsible for the pathogenesis. In chronic
      respiratory diseases, such as chronic obstructive pulmonary disease, asthma,
      diffuse panbronchiolitis and cystic fibrosis, in addition to the supportive
      management for the symptoms, the anti-inflammatory effects of macrolide
      antibiotics were shown to be effective against the over-activation or
      proliferation of T lymphocytes. Recently, we provided physiological and
      pharmacological evidence that macrolide antibiotics, together with calcium
      channel blockers, HMG-CoA reductase inhibitors, and nonsteroidal anti
      inflammatory drugs, effectively suppress the Kv1.3-channel currents in
      lymphocytes, and thus exert anti-inflammatory or immunomodulatory effects. In
      this review article, based on the findings obtained from recent in vivo and in
      vitro studies, we address the novel therapeutic implications of targeting the
      lymphocyte Kv1.3-channels for the treatment of chronic or acute respiratory
      diseases.

PMID- 26206236
TI  - Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated
      septic responses.
AB  - AIM AND OBJECTIVE: The ubiquitous nuclear protein, high-mobility group box 1
      (HMGB1), is released by activated macrophages and human umbilical vein
      endothelial cells (HUVECs) and functions as a late mediator of experimental
      sepsis. Polyozellin, which has been reported to have a variety of biological
      activities including antioxidant and anticancer activity, is the major active
      compound found in edible mushroom (Polyozellus multiplex). In this study, we
      investigated the antiseptic effects and underlying mechanisms of polyozellin
      against HMGB1-mediated septic responses in HUVECs and mice. METHODS: The anti
      inflammatory activities of polyozellin were determined by measuring permeability,
      human neutrophil adhesion and migration, and activation of proinflammatory
      proteins in HMGB1-activated HUVECs and mice. RESULTS: According to the results,
      polyozellin effectively inhibited lipopolysaccharide (LPS)-induced release of
      HMGB1, and suppressed HMGB1-mediated septic responses, such as hyperpermeability,
      adhesion and migration of leukocytes, and expression of cell adhesion molecules.
      In addition, polyozellin suppressed the production of tumor necrosis factor-alpha
      and interleukin (IL)-6, and the activation of nuclear factor-kappaB and
      extracellular signal-regulated kinases 1/2 by HMGB1. CONCLUSION: Collectively,
      these results indicate that P. multiplex containing polyozellin could be
      commercialized as functional food for preventing and treatment of various severe
      vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

PMID- 26206238
TI  - Engineering a dirhodium artificial metalloenzyme for selective olefin
      cyclopropanation.
AB  - Artificial metalloenzymes (ArMs) formed by incorporating synthetic metal
      catalysts into protein scaffolds have the potential to impart to chemical
      reactions selectivity that would be difficult to achieve using metal catalysts
      alone. In this work, we covalently link an alkyne-substituted dirhodium catalyst
      to a prolyl oligopeptidase containing a genetically encoded L-4
      azidophenylalanine residue to create an ArM that catalyses olefin
      cyclopropanation. Scaffold mutagenesis is then used to improve the
      enantioselectivity of this reaction, and cyclopropanation of a range of styrenes
      and donor-acceptor carbene precursors were accepted. The ArM reduces the
      formation of byproducts, including those resulting from the reaction of dirhodium
      carbene intermediates with water. This shows that an ArM can improve the
      substrate specificity of a catalyst and, for the first time, the water tolerance
      of a metal-catalysed reaction. Given the diversity of reactions catalysed by
      dirhodium complexes, we anticipate that dirhodium ArMs will provide many unique
      opportunities for selective catalysis. 

PMID- 26206239
TI  - Foundation doctors' induction experiences.
AB  - BACKGROUND: It is well established that trainee doctors struggle with the
      transition from medical school to starting work and feel unprepared for many
      aspects of their new role. There is evidence that suitable induction experiences
      improve competence and confidence, but available data indicate that trainee
      doctors on the UK Foundation Programme are commonly not experiencing useful
      inductions. The aim of the reported research was to explore trainee doctors'
      experiences with induction during their first year of the Foundation Programme to
      identify the most useful characteristics. METHODS: A questionnaire was designed
      to explore trainee doctors' experiences with induction at two points during their
      first Foundation year, during the first and third of three rotations, to enable
      all induction experiences on offer during the year to be surveyed. Data were
      collected using an anonymous questionnaire distributed during a teaching session,
      with an online version available for those trainees not present. Questions
      gathered information about characteristics of the inductions, usefulness of
      components of the inductions and what gaps exist. RESULTS: 192 Foundation trainee
      doctors completed the questionnaire during Rotation 1 and 165 during Rotation 3.
      The findings indicated that induction experiences at the beginning of the year,
      including the local Preparation for Professional Practice week, were more useful
      than those received for later rotations. Longer inductions were more useful than
      shorter. Departmental inductions were generally only moderately helpful and they
      missed many important characteristics. Gaps in their inductions identified by
      many trainees matched those aspects judged to be most useful by those trainees
      who had experienced these characteristics. CONCLUSIONS: Many Foundation trainee
      doctors are experiencing inadequate inductions, notably at the department level.
      Trainees are starting rotations in new departments without rudimentary knowledge
      about their role and responsibilities in that department, where to find equipment
      and documentation, who to contact and how to contact them, local preferences,
      policies and procedures. Unsurprisingly, trainees who do receive such information
      in their inductions regard it as highly useful. Action is urgently needed to
      improve departmental inductions so that all trainees have the information they
      require to work confidently and competently in each new department they rotate
      into.

PMID- 26206240
TI  - Evolving role of pediatric nurse practitioners.
AB  - PURPOSE: To report and interpret findings from national pediatric nurse
      practitioner (PNP) job analysis surveys reflecting the changes in the knowledge
      and skills required for advanced practice. DATA SOURCES: National role
      delineation studies (RDS) conducted by American Nurses Credentialing Center
      (ANCC) in 2003, 2008, and 2011. CONCLUSIONS: Since the first nurse practitioner
      (NP) program was established in 1965 to train pediatric nurses for advanced
      practice, the role of the PNP has continued to develop. The RDS results
      demonstrate the increased autonomy of PNP's prescription of medication as the top
      work activity category identified, followed by the reporting of suspected abuse,
      exploitation, and/or neglect and immunizing based on current recommendations.
      IMPLICATIONS FOR PRACTICE: Analysis of the changes in role or work activities,
      tied to the knowledge and skills required to perform those activities, can
      provide content for educators updating curriculum, for clinicians to remain
      current in their practice and impact healthcare policy. The current PNP role has
      evolved to meet the workforce demands of providing primary care to the pediatric
      population with increasing complex social and healthcare needs. Role analysis is
      important as NPs move forward to practice to the full extent of their education
      and training.

PMID- 26206241
TI  - Pulmonary edema induced after being buried alive.

PMID- 26206242
TI  - Thrombolysis during continuous chest compression in a patient with cardiac arrest
      due to pulmonary embolism: prolonged CPR-induced spinal cord injury.

PMID- 26206243
TI  - Diagnostic and prognostic value of myeloid-related protein complex 8/14 for
      sepsis.
AB  - OBJECTIVE: The objective of this study is to evaluate the diagnostic and
      prognostic value of myeloid-related protein complex 8/14 (MRP8/14) in septic
      patients in intensive care units. METHODS: Fifty-three cases of healthy people,
      72 cases of systemic inflammatory response syndrome patients, 74 cases of sepsis
      patients, 78 cases of severe sepsis patients, and 76 cases of septic shock
      patients were enrolled in our hospital. Serum MRP8/14 was detected by enzyme
      linked immunosorbent assay, and Mortality in Emergency Department Sepsis (MEDS)
      score was calculated at enrollment. The receiver operating characteristic curve
      was used to analyze the diagnostic value of MRP8/14 for sepsis. The prognostic
      values of MRP8/14 were compared with MEDS score. A 28-day follow-up was performed
      for all patients. RESULTS: Serum MRP8/14 level of control group, systemic
      inflammatory response syndrome group, sepsis group, severe sepsis group, and
      septic shock group was (834.135 +/- 251.662), (2343.213 +/- 901.850), (3163.617
      +/- 912.821), (3941.326 +/- 850.490), and (4131.326 +/- 950.439) ng/mL,
      respectively. Myeloid-related protein complex 8/14 level increased with sepsis
      severity. The area under the receiver operating characteristic curves of MRP8/14
      for sepsis was 0.901 (95% confidence interval, 0.852-0.942).The area under the
      receiver operating characteristic curves of MRP8/14 was greater than that of MEDS
      score in predicting 28-day mortality. Serum MRP8/14 level was significantly
      higher in nonsurvivors than survivors at 28 days' follow-up. In addition, the
      level of MRP8/14 was much higher in septic patients with acute kidney injury
      (AKI) than those without AKI. CONCLUSIONS: Myeloid-related protein complex 8/14
      is valuable for diagnosis and prognostication of sepsis and septic patients with
      AKI in the intensive care unit.

PMID- 26206244
TI  - Suspected esophageal coin--look again.
AB  - A 4-year-old presented to the emergency department, asymptomatic, with the strong
      suspicion (by history, physical examination, and initial radiographic
      interpretation by the emergency physician) of an esophageal coin. Closer
      inspection revealed radiographic signs associated with disk battery ingestion, a
      surgical emergency. In the operating room superimposed coins, mimicking the
      radiographic appearance of a disk (button) battery, were extracted. This case
      highlights the important management differences between ingested coins and
      batteries, the need for cautious interpretation of radiographs, and presents a
      rare mimic of a serious ingestion.

PMID- 26206245
TI  - Effect of aerobic and microaerophilic culture in the growth dynamics of
      Saccharomyces cerevisiae and in training of quiescent and non-quiescent
      subpopulations.
AB  - Saccharomyces cerevisiae is industrially the most important yeast, and its growth
      in different concentrations of oxygen can be used to improve various application
      processes. The aims of this work were to study in aerobic and microaerophilic
      growth conditions the cell size and tendency of morphological changes in S.
      cerevisiae in different stages of growth and to assess the effect of the two
      growth conditions in the differentiation of quiescent and non-quiescent
      subpopulations in the stationary phase. Dissolved oxygen levels in the culture
      medium for aerobic and microaerophilic conditions were 6.6 and 5.2 mg L(-1),
      respectively. In both growth conditions, similar viable cell populations were
      obtained, although in aerobic conditions the stationary phase was reached and the
      quiescent and non-quiescent subpopulations were also differentiated. The
      microaerophilic growth produced a significant reduction in the specific growth
      rate and consequently also in glucose and oxygen consumption. The most notable
      changes in cellular size and morphology occurred with the depletion of glucose
      and oxygen. The concentration of dissolved oxygen in the culture medium
      significantly modulated the growth kinetics of S. cerevisiae and their
      development and differentiation to quiescent cells. This could justify the need
      to readjust small variations in oxygen levels during yeast cultures in
      biotechnological processes. 

PMID- 26206246
TI  - Transapical Valve-in-valve Implantation in Failed Mitral Bioprostheses.

PMID- 26206247
TI  - Safety and Efficacy of New Sirolimus-eluting Stent Models in a Preclinical Study.
AB  - INTRODUCTION AND OBJECTIVES: Initial preclinical studies are required during the
      process of improving polymers, platforms, and drug-eluting systems for new
      coronary stent designs. Our objective was to analyze the efficacy and safety of
      new drug-eluting stent models compared with a conventional stent and
      commercialized drug-eluting stents in an experimental model with healthy porcine
      coronary arteries. METHODS: Sixty stents (conventional stent, new sirolimus
      eluting stents: drug-eluting stents 1, 2 and 3; Cypher((r)) and Xience((r))) were
      randomly placed in the coronary arteries of 20 Large White domestic pigs.
      Angiographic and histomorphometric studies were done 28 days later. RESULTS: The
      stents were implanted at a stent/artery ratio of 1.34+/-0.15, with no significant
      differences between groups. The new stents showed less late loss and angiographic
      restenosis than conventional stents (P=.006 and P<.001, respectively).
      Histologically, restenosis and neointimal area were lower with all the new
      platforms than with the conventional stents (P<.001 for each variable), and no
      differences were found vs the drug-eluting stents on the market. Safety data
      showed that endothelialization was lower with drug-eluting stents than with
      conventional stents, except for drug-eluting stent 3 (P=.084). Likewise,
      inflammation was lower with drug-eluting stent 3 than with other stents.
      CONCLUSIONS: The new drug-eluting stent platforms studied are associated with
      less restenosis than conventional stents and showed no significant differences in
      safety or efficacy vs commercialized drug-eluting stents.

PMID- 26206248
TI  - AtMYB12 expression in tomato leads to large scale differential modulation in
      transcriptome and flavonoid content in leaf and fruit tissues.
AB  - Plants synthesize secondary metabolites, including flavonoids, which play
      important role during various stresses for their survival. These metabolites are
      also considered as health-protective components in functional foods. Flavonols,
      one of the important groups of flavonoids, apart from performing several roles in
      plants have been recognized as potent phytoceuticals for human health. Tomato
      fruits are deficient in this group of flavonoids and have been an important
      target for enhancing the accumulation of flavonols through genetic manipulations.
      In the present study, AtMYB12 transcription factor of the Arabidopsis has been
      expressed under constitutive promoter in tomato. Transgenic tomato lines
      exhibited enhanced accumulation of flavonols and chlorogenic acid (CGA) in leaf
      and fruit accompanied with elevated expression of phenylpropanoid pathway genes
      involved in flavonol biosynthesis. In addition, global gene expression analysis
      in leaf and fruit suggested that AtMYB12 modulates number of molecular processes
      including aromatic amino acid biosynthesis, phytohormone signaling and stress
      responses. Besides this, a differential modulation of the genes in fruits and
      leaves is reported in this study. Taken together, results demonstrate that
      modulation of primary carbon metabolism and other pathways by AtMYB12 in tomato
      may lead to sufficient substrate supply for enhanced content of phenolics in
      general and flavonols in particular. 

PMID- 26206250
TI  - The Emergence of Family-specific Support Constructs: Cross-level Effects of
      Family-supportive Supervision and Family-Supportive Organization Perceptions on
      Individual Outcomes.
AB  - Implicit to the definitions of both family-supportive supervision (FSS) and
      family-supportive organization perceptions (FSOP) is the argument that these
      constructs may manifest at a higher (e.g. group or organizational) level. In line
      with these conceptualizations, grounded in tenants of conservation of resources
      theory, we argue that FSS and FSOP, as universal resources, are emergent
      constructs at the organizational level, which have cross-level effects on work
      family conflict and turnover intentions. To test our theoretically derived
      hypotheses, a multilevel model was examined in which FSS and FSOP at the unit
      level predict individual work-to-family conflict, which in turn predicts turnover
      intentions. Our hypothesized model was generally supported. Collectively, our
      results point to FSOP serving as an explanatory mechanism of the effects that
      mutual perceptions of FSS have on individual experiences of work-to-family
      conflict and turnover intentions. Lagged (i.e. overtime) cross-level effects of
      the model were also confirmed in supplementary analyses. Our results extend our
      theoretical understanding of FSS and FSOP by demonstrating the utility of
      conceptualizing them as universal resources, opening up a variety of avenues for
      future research. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26206249
TI  - Role of neuroimaging in multidisciplinary approach towards Non-Alzheimer's
      dementia.
AB  - Dementia is defined as chronic deterioration of intellectual function and
      cognitive skills significant enough to interfere with the ability to perform
      daily activities. Recent advances in the treatment of dementia have renewed
      interest in the use of various neuroimaging techniques that can assist in the
      diagnosis and differentiation of various subtypes. Neuroimaging and computational
      techniques have helped the radiological community to monitor disease progression
      of various neurodegenerative conditions presenting with dementia, such as
      Alzheimer disease, frontotemporal lobe dementia (FTLD), progressive supranuclear
      palsy (PSP) and multisystem atrophy-cerebellar variant (MSA-C), and their
      response to newer therapies. Prompt identification of treatable or reversible
      forms of dementia, such as tumours, subdural haemorrhage and intracranial dAVF,
      is crucial for the effective management of these conditions. It is also prudent
      to recognize the imaging spectrum of metabolic, infective and autoimmune diseases
      with rapidly progressing dementia, such as methanol toxicity, central pontine
      myelinolysis (CPM), delayed post hypoxic leukoencephalopathy (DPHL), HIV,
      Creutzfeldt-Jakob Disease (CJD), Sjogren's syndrome, multiple sclerosis (MS),
      radiation necrosis and Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS), which
      are difficult to treat and often require palliative care. This pictorial review
      emphasizes various non-Alzheimer's dementia entities and discusses their imaging
      highlights. Teaching Points * Non Alzheimer's dementia constitutes a broad
      spectrum of conditions. * Neuroimaging plays an important role in differentiating
      treatable from irreversible dementia. * Neuroimaging is often non-specific in
      early stages of neurodegenerative conditions with dementia. * Neuroimaging plays
      an important role in the multimodal approach towards management of dementia. 

PMID- 26206251
TI  - Distinct hippocampal functional networks revealed by tractography-based
      parcellation.
AB  - Recent research suggests the anterior and posterior hippocampus form part of two
      distinct functional neural networks. Here we investigate the structural
      underpinnings of this functional connectivity difference using diffusion-weighted
      imaging-based parcellation. Using this technique, we substantiated that the
      hippocampus can be parcellated into distinct anterior and posterior segments.
      These structurally defined segments did indeed show different patterns of resting
      state functional connectivity, in that the anterior segment showed greater
      connectivity with temporal and orbitofrontal cortex, whereas the posterior
      segment was more highly connected to medial and lateral parietal cortex.
      Furthermore, we showed that the posterior hippocampal connectivity to memory
      processing regions, including the dorsolateral prefrontal cortex,
      parahippocampal, inferior temporal and fusiform gyri and the precuneus, predicted
      interindividual relational memory performance. These findings provide important
      support for the integration of structural and functional connectivity in
      understanding the brain networks underlying episodic memory.

PMID- 26206253
TI  - The epigenetic footprint of poleward range-expanding plants in apomictic
      dandelions.
AB  - Epigenetic modifications, such as DNA methylation variation, can generate
      heritable phenotypic variation independent of the underlying genetic code.
      However, epigenetic variation in natural plant populations is poorly documented
      and little understood. Here, we test whether northward range expansion of
      obligate apomicts of the common dandelion (Taraxacum officinale) is associated
      with DNA methylation variation. We characterized and compared patterns of genetic
      and DNA methylation variation in greenhouse-reared offspring of T. officinale
      that were collected along a latitudinal transect of northward range expansion in
      Europe. Genetic AFLP and epigenetic MS-AFLP markers revealed high levels of local
      diversity and modest but significant heritable differentiation between sampling
      locations and between the southern, central and northern regions of the transect.
      Patterns of genetic and epigenetic variation were significantly correlated,
      reflecting the genetic control over epigenetic variation and/or the accumulation
      of lineage-specific spontaneous epimutations, which may be selectively neutral.
      In addition, we identified a small component of DNA methylation differentiation
      along the transect that is independent of genetic variation. This epigenetic
      differentiation might reflect environment-specific induction or, in case the DNA
      methylation variation affects relevant traits and fitness, selection of heritable
      DNA methylation variants. Such generated epigenetic variants might contribute to
      the adaptive capacity of individual asexual lineages under changing environments.
      Our results highlight the potential of heritable DNA methylation variation to
      contribute to population differentiation along ecological gradients. Further
      studies are needed using higher resolution methods to understand the functional
      significance of such natural occurring epigenetic differentiation. 

PMID- 26206252
TI  - Control of Apoptosis in Treatment and Biology of Pancreatic Cancer.
AB  - Pancreatic cancer is estimated to be the 12th most common cancer in the United
      States in 2014 and yet this malignancy is the fourth leading cause of cancer
      related death in the United States. Late detection and resistance to therapy are
      the major causes for its dismal prognosis. Apoptosis is an actively orchestrated
      cell death mechanism that serves to maintain tissue homoeostasis. Cancer develops
      from normal cells by accruing significant changes through one or more mechanisms,
      leading to DNA damage and mutations, which in a normal cell would induce this
      programmed cell death pathway. As a result, evasion of apoptosis is one of the
      hallmarks of cancer cells. PDAC is notoriously resistant to apoptosis, thereby
      explaining its aggressive nature and resistance to conventional treatment
      modalities. The current review is focus on understanding different intrinsic and
      extrinsic pathways in pancreatic cancer that may affect apoptosis in this
      disease.

PMID- 26206254
TI  - Meta-analysis of KRAS mutations and survival after resection of colorectal liver
      metastases.
AB  - BACKGROUND: In patients with advanced colorectal cancer, KRAS mutation status
      predicts response to treatment with monoclonal antibody targeting the epithelial
      growth factor receptor (EGFR). Recent reports have provided evidence that KRAS
      mutation status has prognostic value in patients with resectable colorectal liver
      metastases (CLM) irrespective of treatment with chemotherapy or anti-EGFR
      therapy. A meta-analysis was undertaken to clarify the impact of KRAS mutation on
      outcomes in patients with resectable CLM. METHODS: PubMed, Embase and Cochrane
      Library databases were searched systematically to identify full-text articles
      reporting KRAS-stratified overall (OS) or recurrence-free (RFS) survival after
      resection of CLM. Hazard ratios (HRs) and 95 per cent c.i. from multivariable
      analyses were pooled in meta-analyses, and a random-effects model was used to
      calculate weight and overall results. RESULTS: The search returned 355 articles,
      of which 14, including 1809 patients, met the inclusion criteria. Eight studies
      reported OS after resection of CLM in 1181 patients. The mutation rate was 27.6
      per cent, and KRAS mutation was negatively associated with OS (HR 2.24, 95 per
      cent c.i. 1.76 to 2.85). Seven studies reported RFS after resection of CLM in 906
      patients. The mutation rate was 28.0 per cent, and KRAS mutation was negatively
      associated with RFS (HR 1.89, 1.54 to 2.32). CONCLUSION: KRAS mutation status is
      a prognostic factor in patients undergoing resection of colorectal liver
      metastases and should be considered in the evaluation of patients having liver
      resection.

PMID- 26206255
TI  - Age-shifting in malaria incidence as a result of induced immunological deficit: a
      simulation study.
AB  - Effective population-level interventions against Plasmodium falciparum malaria
      lead to age-shifts, delayed morbidity or rebounds in morbidity and mortality
      whenever they are deployed in ways that do not permanently interrupt
      transmission. When long-term intervention programmes target specific age-groups
      of human hosts, the age-specific morbidity rates ultimately adjust to new steady
      states, but it is very difficult to study these rates and the temporal dynamics
      leading up to them empirically because the changes occur over very long time
      periods. This study investigates the age and magnitude of age- and time- shifting
      of incidence induced by either pre-erythrocytic vaccination (PEV) programmes or
      seasonal malaria chemo-prevention (SMC), using an ensemble of individual-based
      stochastic simulation models of P. falciparum dynamics. The models made various
      assumptions about immunity decay, transmission heterogeneity and were
      parameterized with data on both age-specific infection and disease incidence at
      different levels of exposure, on the durations of different stages of the
      parasite life-cycle and on human demography. Effects of transmission intensity,
      and of levels of access to malaria treatment were considered. While both PEV and
      SMC programmes are predicted to have overall strongly positive health effects, a
      shift of morbidity into older children is predicted to be induced by either
      programme if transmission levels remain static and not reduced by other
      interventions. Predicted shifting of burden continue into the second decade of
      the programme. Even if long-term surveillance is maintained it will be difficult
      to avoid mis-attribution of such long-term changes in age-specific morbidity
      patterns to other factors. Conversely, short-lived transient changes in incidence
      measured soon after introduction of a new intervention may give over-positive
      views of future impacts. Complementary intervention strategies could be designed
      to specifically protect those age-groups at risk from burden shift. 

PMID- 26206256
TI  - Automated Computed Tomography-Ultrasound Cross-Modality 3-D Contouring Algorithm
      for Prostate.
AB  - A novel fully automated algorithm is introduced for 3-D cross-modality image
      segmentation of the prostate, based on the simultaneous use of co-registered
      computed tomography (CT) and 3-D ultrasound (US) images. By use of a Gabor
      feature detector, the algorithm can outline in three dimensions and in cross
      modality the prostate, and it can be trained and optimized on specific patient
      populations. We applied it to 16 prostate cancer patients and evaluated the
      conformity between the automatically segmented prostate contours and the contours
      manually outlined by an experienced physician, on the CT-US fusion, using the
      mean distance to conformity (MDC) index. When only the CT scans were used, the
      average MDC value was 4.5 +/- 1.7 mm (maximum value = 9.0 mm). When the US scans
      also were considered, the mean +/- standard deviation was reduced to 3.9 +/- 0.7
      mm (maximum value = 5.5 mm). The cross-modality approach acted on all the largest
      distance values, reducing them to acceptable discrepancies.

PMID- 26206257
TI  - A Computerized System to Assess Axillary Lymph Node Malignancy from Sonographic
      Images.
AB  - A computational approach to classifying axillary lymph node metastasis in
      sonographic images is described. One hundred five ultrasound images of axillary
      lymph nodes from patients with breast cancer were evaluated (81 benign and 24
      malignant), and each lymph node was manually segmented, delineating both the
      whole lymph node and internal hilum surfaces. Normalized signed distance
      transforms were computed from the segmented boundaries of both structures, and
      each pixel was then assigned coordinates in a 3-D feature space according to the
      pixel's intensity, its signed distance to the node boundary and its signed
      distance to the hilum boundary. Three-dimensional histograms over the feature
      space were accumulated for each node by summing over all pixels, and the bin
      counts served as predictor inputs to a support vector machine learning algorithm.
      Repeated random sampling of 80/25 train/test splits was used to estimate
      generalization performance and generate receiver operating characteristic curves.
      The optimal classifier had an area under the receiver operating characteristic
      curve of 0.95 and sensitivity and specificity of 0.90 and 0.90. Our results
      indicate the feasibility of axillary nodal staging with computerized analysis. 

PMID- 26206258
TI  - Time to initiation of adjuvant chemotherapy in patients with rapidly
      proliferating early breast cancer.
AB  - AIM: To evaluate the optimal time interval from definitive surgery to commencing
      chemotherapy in early breast cancer (EBC). PATIENTS AND METHODS: The relationship
      between time to initiation of adjuvant chemotherapy (TTC), calculated in weeks,
      and disease-free (DFS) or overall survival (OS), was assessed in 921 EBC patients
      with rapidly proliferating tumours (thymidine labelling index >3% or G3 or Ki67
      >20%), randomised in a phase III clinical trial (NCT01031030) to receive
      chemotherapy with or without anthracyclines (epirubicin->cyclophosphamide,
      methotrexate and fluorouracil (CMF) versus CMF->epirubicin versus CMF). DFS, OS
      and 95% confidence intervals (95% confidence interval (CI)) were calculated by
      the Kaplan-Meier method. Multivariate Cox analysis was performed in relation with
      nodal involvement, oestrogen receptor and human epidermal growth factor receptor
      2 (HER2) status, Ki67 value, type of adjuvant chemotherapy, menopausal status and
      tumour size. RESULTS: At a median follow-up of 105 months (range 2-188), a
      prolonged TTC resulted in a significant increase in the risk of relapse: hazard
      ratio (HR) 1.15 (95% CI 1.02-1.30, p=0.019). Using a backward elimination
      procedure, TTC, tumour size and nodal involvement remained significantly
      associated with DFS. A time-dependent receiver-operating characteristic (ROC)
      curve analysis was subsequently utilised to evaluate the best cut-off for TTC,
      identifying 7 weeks as the best threshold for longer OS (p=0.043): 8-year OS 88%
      (95% CI 85-90) for patients with a TTC <7 weeks and 78% (95% CI 68-87) for the
      other group. CONCLUSIONS: Our results confirm that a shorter TTC may reduce
      relapses and possibly also improve clinical outcome in patients with highly
      proliferating EBC.

PMID- 26206259
TI  - The use of buttress plates in the management of acetabular fractures with
      quadrilateral plate involvement: is it still a valid option?
AB  - PURPOSE: The primary aim of this study was to report on the mid-term outcomes
      after quadrilateral plate reconstruction of acetabular fractures using a
      buttress/spring plate through an ilioinguinal approach. METHODS: Between 2003 and
      2011, 30 adult patients (25 males) with mean age 54 years (range 17-80) who
      underwent surgical fixation for an acetabular fracture and had minimum follow up
      of 24 months (mean 46.2, range 24-78.6) were retrospectively reviewed. Standard
      demographics, admission and hospitalization data (concomitant injuries, number of
      operative procedures, time to operating theatre, early and late complications)
      were correlated to the clinical (Harris Hip Score) and radiological (Matta
      Reduction Score and Matta Arthritis Score) outcome. RESULTS: Three patients
      underwent a Total Hip Replacement. Functional score was excellent in 17 (56.6 %),
      good in 4 (13.3 %), fair in 6 (20 %) and poor in 3 (10 %) cases. Surgery-related
      complications included two patients with temporary lateral femoral cutaneous
      palsy and three with heterotopic ossification. The quality of the postoperative
      reduction was associated to Harris Hip Score (p = 0.015) and postoperative
      arthritis (p = 0.010). Strong association was evident between age and both post
      operative reduction (p = 0.010) and arthritis (p = 0.014). The presence of
      quadrilateral plate comminution and gull-sign were associated to poor post
      operative reduction (p = 0.016) and low Harris Hip Score (p = 0.049)
      respectively. CONCLUSION: Quadrilateral plate reconstruction with a buttress
      plate though the ilioinguinal approach remains a valid method of fixation in
      acetabular surgery. Additional studies are needed to compare the efficiency of
      this method to new surgical approaches and fixation implants.

PMID- 26206260
TI  - Is computed tomography an accurate and reliable method for measuring total knee
      arthroplasty component rotation?
AB  - PURPOSE: Computed tomography (CT) is widely used to assess component rotation in
      patients with poor results after total knee arthroplasty (TKA). The purpose of
      this study was to simultaneously determine the accuracy and reliability of CT in
      measuring TKA component rotation. METHODS: TKA components were implanted in dry
      bone models and assigned to two groups. The first group (n = 7) had variable
      femoral component rotations, and the second group (n = 6) had variable tibial
      tray rotations. CT images were then used to assess component rotation. Accuracy
      of CT rotational assessment was determined by mean difference, in degrees,
      between implanted component rotation and CT-measured rotation. Intraclass
      correlation coefficient (ICC) was applied to determine intra-observer and inter
      observer reliability. RESULTS: Femoral component accuracy showed a mean
      difference of 2.5 degrees  and the tibial tray a mean difference of 3.2 degrees .
      There was good intra- and inter-observer reliability for both components, with a
      femoral ICC of 0.8 and 0.76, and tibial ICC of 0.68 and 0.65, respectively.
      CONCLUSIONS: CT rotational assessment accuracy can differ from true component
      rotation by approximately 3 degrees  for each component. It does, however, have
      good inter- and intra-observer reliability.

PMID- 26206261
TI  - Collagen type I coating stimulates bone regeneration and osteointegration of
      titanium implants in the osteopenic rat.
AB  - PURPOSE: To investigate the effects of titanium implants functionalised with
      collagen type I (TiColl) on bone regeneration and osteointegration in a healthy
      and osteopenic rat animal model. METHOD: TiColl screws were implanted into the
      femoral condyles of healthy and osteopenic rats and compared with acid-etched
      titanium (Ti) screws. The osteointegration process was evaluated by a
      complementary approach combining microtomographic, histological,
      histomorphometric and biomechanical investigations at four and 12 weeks. RESULTS:
      The TiColl screw also ensured a greater mechanical stability; the push-out values
      for TiColl screws increased from four to 12 weeks (+28 %). The energy necessary
      to detach the bone from the screw was significantly higher for TiColl
      functionalised screws in comparison to Ti screws (+23 %) at 12 weeks.
      Histomorphometric investigation revealed that total bone-to-implant contact was
      higher in TiColl screws in comparison to Ti screws (P < 0.05) and at epiphyseal
      level, increased bone-to-implant contact was found with TiColl screws in
      comparison to Ti screws (P < 0.05) in an ovariectomy (OVX) condition. A
      significant increase in the measured total bone ingrowth from four to 12 weeks
      was detected for both materials, but more significant for the TiColl material (P
      < 0.0005). Finally, bone ingrowth in the TiColl group was significantly higher (P
      < 0.005) in comparison to that of Ti screws in the SHAM condition at metaphyseal
      level at 12 weeks. CONCLUSION: The present results showed that TiColl is
      effective in promoting implant osteointegration even in compromised bone.

PMID- 26206262
TI  - BODIPY: A Highly Versatile Platform for the Design of Bimodal Imaging Probes.
AB  - In molecular imaging, multimodal imaging agents can provide complementary
      information, for improving the accuracy of disease diagnosis or enhancing patient
      management. In particular, optical/nuclear imaging may find important preclinical
      and clinical applications. To simplify the preparation of dual-labeled imaging
      agents, we prepared versatile monomolecular multimodal imaging probe (MOMIP)
      platforms containing both a fluorescent dye (BODIPY) and a metal chelator
      (polyazamacrocycle). One of the MOMIP was conjugated to a cyclopeptide (i.e.,
      octreotide) and radiolabeled with (111) In. In vitro and in vivo studies of the
      resulting bioconjugate were conducted, highlighting the potential of these BODIPY
      based bimodal probes. This work also confirmed that the biovector and/or the
      bimodal probes must be chosen carefully, due to the impact of the MOMIP on the
      overall properties of the resulting imaging agent. 

PMID- 26206263
TI  - Red: an intelligent, rapid, accurate tool for detecting repeats de-novo on the
      genomic scale.
AB  - BACKGROUND: With rapid advancements in technology, the sequences of thousands of
      species' genomes are becoming available. Within the sequences are repeats that
      comprise significant portions of genomes. Successful annotations thus require
      accurate discovery of repeats. As species-specific elements, repeats in newly
      sequenced genomes are likely to be unknown. Therefore, annotating newly sequenced
      genomes requires tools to discover repeats de-novo. However, the currently
      available de-novo tools have limitations concerning the size of the input
      sequence, ease of use, sensitivities to major types of repeats, consistency of
      performance, speed, and false positive rate. RESULTS: To address these
      limitations, I designed and developed Red, applying Machine Learning. Red is the
      first repeat-detection tool capable of labeling its training data and training
      itself automatically on an entire genome. Red is easy to install and use. It is
      sensitive to both transposons and simple repeats; in contrast, available tools
      such as RepeatScout and ReCon are sensitive to transposons, and WindowMasker to
      simple repeats. Red performed consistently well on seven genomes; the other tools
      performed well only on some genomes. Red is much faster than RepeatScout and
      ReCon and has a much lower false positive rate than WindowMasker. On human genes
      with five or more copies, Red was more specific than RepeatScout by a wide
      margin. When tested on genomes of unusual nucleotide compositions, Red located
      repeats with high sensitivities and maintained moderate false positive rates. Red
      outperformed the related tools on a bacterial genome. Red identified 46,405 novel
      repetitive segments in the human genome. Finally, Red is capable of processing
      assembled and unassembled genomes. CONCLUSIONS: Red's innovative methodology and
      its excellent performance on seven different genomes represent a valuable
      advancement in the field of repeats discovery.

PMID- 26206264
TI  - Functional microRNA high throughput screening reveals miR-9 as a central
      regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of cancer
      related deaths, reflecting the aggressiveness of this type of cancer and the
      absence of effective therapeutic regimens. MicroRNAs have been involved in the
      pathogenesis of different types of cancers, including liver cancer. Our aim was
      to identify microRNAs that have both functional and clinical relevance in HCC and
      examine their downstream signaling effectors. METHODS: MicroRNA and gene
      expression levels were measured by quantitative real-time PCR in HCC tumors and
      controls. A TargetScan algorithm was used to identify miR-9 downstream direct
      targets. RESULTS: A high-throughput screen of the human microRNAome revealed 28
      microRNAs as regulators of liver cancer cell invasiveness. MiR-9, miR-21 and miR
      224 were the top inducers of HCC invasiveness and also their expression was
      increased in HCC relative to control liver tissues. Integration of the microRNA
      screen and expression data revealed miR-9 as the top microRNA, having both
      functional and clinical significance. MiR-9 levels correlated with HCC tumor
      stage and miR-9 overexpression induced SNU-449 and HepG2 cell growth,
      invasiveness and their ability to form colonies in soft agar. Bioinformatics and
      3'UTR luciferase analyses identified E-cadherin (CDH1) and peroxisome
      proliferator-activated receptor alpha (PPARA) as direct downstream effectors of
      miR-9 activity. Inhibition of PPARA suppressed CDH1 mRNA levels, suggesting that
      miR-9 regulates CDH1 expression directly through binding in its 3'UTR and
      indirectly through PPARA. On the other hand, miR-9 inhibition of overexpression
      suppressed HCC tumorigenicity and invasiveness. PPARA and CDH1 mRNA levels were
      decreased in HCC relative to controls and were inversely correlated with miR-9
      levels. CONCLUSIONS: Taken together, this study revealed the involvement of the
      miR-9/PPARA/CDH1 signaling pathway in HCC oncogenesis.

PMID- 26206266
TI  - Hollow Au/Ag nanostars displaying broad plasmonic resonance and high surface
      enhanced Raman sensitivity.
AB  - Bimetallic Au/Ag hollow nanostar (HNS) nanoparticles with different morphologies
      were prepared in this work. These nanoplatforms were obtained by changing the
      experimental conditions (concentration of silver and chemical reductors,
      hydroxylamine and citrate) and by using Ag nanostars as template nanoparticles
      (NPs) through galvanic replacement. The goal of this research was to create
      bimetallic Au/Ag star-shaped nanoparticles with advanced properties displaying a
      broader plasmonic resonance, a cleaner exposed surface, and a high concentration
      of electromagnetic hot spots on the surface provided by the special morphology of
      nanostars. The size, shape, and composition of Ag as well as their optical
      properties were studied by extinction spectroscopy, hyperspectral dark field
      microscopy, transmission and scanning electron microscopy (TEM and SEM), and
      energy dispersive X-ray spectroscopy (EDX). Finally, the surface-enhanced Raman
      scattering (SERS) activity of these HNS was investigated by using thioflavin T, a
      biomarker of the beta-amyloid fibril formation, responsible for Alzheimer's
      disease. Lucigenin, a molecule displaying different SERS activities on Au and Ag,
      was also used to explore the presence of these metals on the NP surface. Thus, a
      relationship between the morphology, plasmon resonance and SERS activity of these
      new NPs was made. 

PMID- 26206265
TI  - Ethanol activates midkine and anaplastic lymphoma kinase signaling in
      neuroblastoma cells and in the brain.
AB  - Alcohol engages signaling pathways in the brain. Midkine (MDK) is a neurotrophic
      factor that is over-expressed in the prefrontal cortex of alcoholics. MDK and one
      of its receptors, anaplastic lymphoma kinase (ALK), also regulate behavioral
      responses to ethanol in mice. The goal of this study was to determine whether MDK
      and ALK expression and signaling are activated by ethanol. We found that ethanol
      treatment of neuroblastoma cells increased MDK and ALK expression. We also
      assessed activation of ALK by ethanol in cells and found that ALK and ALK
      dependent extracellular signal-regulated kinase (ERK) and signal transducer and
      activator of transcription 3 (STAT3) phosphorylation increased rapidly with
      ethanol exposure. Similarly, treatment of cells with recombinant MDK protein
      increased ALK, ERK and STAT3 phosphorylation, suggesting that ethanol may utilize
      MDK to activate ALK signaling. In support of this, transfection of cells with MDK
      siRNAs attenuated ALK signaling in response to ethanol. Ethanol also activates
      ERK signaling in the brain. We found that inhibition of ALK or knockout of MDK
      attenuated ethanol-induced ERK phosphorylation in mouse amygdala. These results
      demonstrate that ethanol engages MDK and ALK signaling, which has important
      consequences for alcohol-induced neurotoxicity and the regulation of behaviors
      related to alcohol abuse.

PMID- 26206267
TI  - Genetic and Environmental Contributions to Personality Trait Stability and Change
      Across Adolescence: Results From a Japanese Twin Sample.
AB  - We examined developmental trends and sources of stability and change in
      adolescent personality by using twin data collected from 1981 to 2010 (273
      monozygotic (MZ) and 48 dizygotic (DZ) twin pairs) from a secondary school
      affiliated with the University of Tokyo. Phenotypic analyses showed high rank
      order stability and substantial mean-level increases in neuroticism and declines
      in extraversion over the adolescent years. Longitudinal bivariate genetic
      analyses revealed that the best-fitting model for adolescent personality includes
      additive genetic and non-shared environmental influences. Heritability estimates
      ranged approximately from 0.30 to 0.60. Additionally, three-year stability in
      adolescent personality was influenced mainly by genetic factors, and there were
      both genetic and environmental innovations in mid-adolescence. Our findings
      suggest that both genetic and environmental effects have significant roles in the
      etiology of personality development across adolescence. 

PMID- 26206268
TI  - Risk of spontaneous abortion and other pregnancy outcomes in 15-25 year old women
      exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United
      Kingdom.
AB  - BACKGROUND: We assessed the risk of spontaneous abortion (SA) after inadvertent
      exposure to HPV-16/18-vaccine during pregnancy using an observational cohort
      design. METHODS: The study population included women aged 15-25 years registered
      with the Clinical Practice Research Datalink General Practice OnLine Database in
      the United Kingdom (UK), who received at least one HPV-16/18-vaccine dose between
      1st September 2008 and 30th June 2011. Exposed women had the first day of
      gestation between 30 days before and 45 days (90 days for the extended exposure
      period) after any HPV-16/18-vaccine dose. Non-exposed women had the first day of
      gestation 120 days-18 months after the last dose. SA defined as foetal loss
      between weeks 1 and 23 of gestation (UK definition). RESULTS: The frequency of SA
      was 11.6% (among 207 exposed) and 9.0% (632 non-exposed), women: hazard ratio
      (HR) adjusted for age at first day of gestation 1.30 (95% confidence interval:
      0.79-2.12). Sensitivity analysis per number of doses administered (-30 to +45-day
      risk period) showed a HR for SA of 1.11 (0.64-1.91) for 18/178 women with one
      dose during the risk period versus 2.55 (1.09-5.93) in 6/29 women with two doses
      within a 4-5 weeks period. The proportion of pre-term/full-term/postterm
      deliveries, small/large for gestational age infants, and birth defects was not
      significantly different between exposed and non-exposed women. Results were
      consistent using a (United States) SA definition of foetal loss between weeks 1
      19 and/or the extended risk period. CONCLUSION: There was no evidence of an
      increased risk of SA and other adverse pregnancy outcomes in young women
      inadvertently HPV-16/18-vaccinated around gestation. Nevertheless, women who are
      pregnant or trying to become pregnant are advised to postpone vaccination until
      completion of pregnancy.

PMID- 26206269
TI  - Enhanced immunogenicity of a respiratory syncytial virus (RSV) F subunit vaccine
      formulated with the adjuvant GLA-SE in cynomolgus macaques.
AB  - Respiratory syncytial virus (RSV) causes significant disease in elderly adults,
      but an effective vaccine is not yet available. We have previously reported that
      vaccines consisting of engineered respiratory syncytial virus soluble fusion
      protein (RSV sF) adjuvanted with glucopyranosyl lipid A (GLA) in an oil-in-water
      emulsion (stable emulsion [SE]) induce RSV F-specific T and B cell responses in
      mice and rats that protect from viral challenge. Here, we evaluated the
      immunogenicity of GLA-SE adjuvanted RSV sF vs unadjuvanted RSV sF vaccines in
      cynomolgus macaques (Macaca fascicularis). RSV F-specific IgG, RSV neutralizing
      antibodies, and RSV F-specific T cell IFNgamma ELISPOT responses induced by GLA
      SE adjuvanted RSV sF peaked at week 6 at significantly higher levels than
      achieved by unadjuvanted RSV sF and remained detectable through week 24,
      demonstrating response longevity. Two weeks after a week 24 booster immunization,
      humoral and cellular responses reached levels similar to those seen at the
      earlier peak response. Importantly, the GLA-SE adjuvanted RSV sF vaccine induced
      cross-neutralizing antibodies to other RSV A and B strains as well as F-specific
      IgA and IgG memory B cells. GLA-SE adjuvanted RSV sF was also demonstrated to
      drive a Th1-biased response characterized by more IFNgamma than IL-4. This study
      indicates that a GLA-SE adjuvanted RSV sF vaccine induces robust humoral and Th1
      biased cellular immunity in non-human primates and may benefit human populations
      at risk for RSV disease. 

PMID- 26206270
TI  - Optimization of influenza A vaccine virus by reverse genetic using chimeric HA
      and NA genes with an extended PR8 backbone.
AB  - The yield of influenza antigen production may significantly vary between vaccine
      strains; for example the A/California/07/09 (H1N1)-X179A vaccine virus, prepared
      during 2009 influenza pandemic, presented a low antigen yield in eggs compared to
      other seasonal H1N1 reassortants. In this study a bi-chimeric virus expressing HA
      and NA genes with A/Puerto Rico/8/34 (H1N1) (PR8) and X179A domains was rescued
      by reverse genetics using a mixture of Vero/CHOK1 cell lines (Medina et al. [7]).
      The bi-chimeric virus obtained demonstrated to yield much larger amounts of HA
      than X179A in eggs as measured by single-radial-immunodiffusion (SRID), the
      reference method to quantify HA protein in influenza vaccine. Such kind of
      optimized virus using PR8 backbone derived chimeric glycoproteins could be used
      as improved seed viruses for vaccine production. 

PMID- 26206271
TI  - Iron primes 3T3-L1 adipocytes to a TLR4-mediated inflammatory response.
AB  - OBJECTIVE: Iron participates in several mechanisms involving inflammation and
      innate immunity, yet the dysregulation of its homeostasis is a major cause of
      metabolic syndrome. Adipocytes should play a major role in iron metabolism, as an
      impairment in iron turnover is closely related to insulin resistance, obesity,
      and type 2 diabetes. The aim of this study was to investigate the role of iron in
      an in vitro-inflamed adipocyte model. METHODS: Gene expression of tumor necrosis
      factor-alpha, interleukin-6, inflammatory chemokines (CCL3, CCL4, and CXCL12),
      and molecules involved in iron metabolism were evaluated in an in vitro mouse 3T3
      L1 cell model. Cells underwent treatment with FeSO4 heptahydrate and
      lipopolysaccharide (LPS) stimulation. Toll-like receptor 4 (TLR4) membrane
      expression, lipid droplet immunohystochemistry, and lipolysis were also
      evaluated. RESULTS: Iron sulphate heptahydrate elicited gene expression of
      hepcidin, hemojuvelin, and ferroportin at different time courses. Additionally,
      it activated lipolysis but did not trigger any adipokine gene expression. When
      cells treated with physiological doses of iron were also stimulated with LPS, an
      enhancement in the LPS-induced gene expression of cytokines and chemokines was
      observed. The enhancement occurred with different patterns depending on different
      time courses and investigated genes, showing its maximal effect for IL-6 gene
      expression. CONCLUSIONS: FeSO4 heptahydrate at a relatively physiological dose,
      induced gene expression of iron modulatory proteins and also enhanced RNA
      transcripts of several inflammatory cytokines and chemokines through a
      priming/synergistic mechanism involving membrane TLR4.

PMID- 26206272
TI  - Axial fluoride binding by lanthanide DTMA complexes alters the local crystal
      field, resulting in dramatic spectroscopic changes.
AB  - Addition of fluoride to aqueous solutions of lanthanide complexes of DTMA results
      in the formation of ternary complexes of the form [F.Ln.DTMA](2+) in which an
      axial solvent molecule is displaced by fluoride. [F.Ln.DTMA](2+) and
      [H2O.Ln.DTMA](3+) are in exchange on a timescale of around 1 s. Dramatic changes
      are observed in both the NMR and luminescence spectra of the complexes: these are
      consistent with a change in the nature of the magnetic anisotropy at the
      paramagnetic lanthanide centre, itself arising from a change in the local crystal
      field. Study of paramagnetic lanthanide complexes with anisotropic electronic
      distributions reveals that, upon replacing water with fluoride, there is an
      inversion of the sign, and a significant reduction in the magnitude, of the
      crystal field term that defines the nature of the pseudocontact shift. 

PMID- 26206273
TI  - Otologic Manifestations of Autosomal Recessive Congenital Ichthyosis in Children.
AB  - BACKGROUND: Few studies have investigated ear involvement in nonsyndromic
      autosomal recessive congenital ichthyosis (ARCI). OBJECTIVES: To assess the type
      and frequency of otologic manifestations of ARCI in patients under follow-up at
      the pediatric dermatology department of our hospital. MATERIALS AND METHODS: We
      prospectively studied the presence of ear pain, ear itching, tinnitus, otitis,
      cerumen impaction, accumulation of epithelial debris, and hearing loss. Daily
      hygiene measures, topical treatments, medical-surgical interventions, and
      frequency of visits to an ear, nose, and throat (ENT) specialist were noted in
      the patients' medical records. Ear examination and hearing tests were performed
      in all cases. RESULTS: Ten patients were studied: 2 had a self-healing collodion
      baby phenotype and 8 had ichthyosis. There was mention of otologic manifestations
      in the records of all 8 patients with ichthyosis (100%); 6 of these patients
      (75%) had abnormalities in the external auditory canal examination and 2 (25%)
      had conductive hearing loss. Our findings are limited by the small number of
      patients studied, all of whom were younger than 19 years. CONCLUSIONS: The
      involvement of both dermatologists and ENT specialists in the management of
      patients with ichthyosis is crucial to ensure the application of the best
      therapeutic and preventive measures. More studies are needed to assess the
      prevalence and impact on quality of life of ear involvement in patients with
      ichthyosis and to determine the optimal interval between ENT visits for these
      patients.

PMID- 26206274
TI  - Trichorrhexis nodosa: a distinctive presentation after tumour necrosis factor
      alpha inhibitor therapy.

PMID- 26206275
TI  - The health and economic impact of vaccination with 7-valent pneumococcal vaccine
      (PCV7) during an annual influenza epidemic and influenza pandemic in China.
AB  - BACKGROUND: China has experienced several severe outbreaks of influenza over the
      past century: 1918, 1957, 1968, and 2009. Influenza itself can be deadly;
      however, the increase in mortality during an influenza outbreak is also
      attributable to secondary bacterial infections, specifically pneumococcal
      disease. Given the history of pandemic outbreaks and the associated morbidity and
      mortality, we investigated the cost-effectiveness of a PCV7 vaccination program
      in China from the context of typical and pandemic influenza seasons. METHODS: A
      decision-analytic model was employed to evaluate the impact of a 7-valent
      pneumococcal vaccine (PCV7) infant vaccination program on the incidence,
      mortality, and cost associated with pneumococcal disease during a typical
      influenza season (15% flu incidence) and influenza pandemic (30% flu incidence)
      in China. The model incorporated Chinese data where available and included both
      direct and indirect (herd) effects on the unvaccinated population, assuming a
      point in time following the initial introduction of the vaccine where the impact
      of the indirect effects has reached a steady state, approximately seven years
      following the implementation of the vaccine program. Pneumococcal disease
      incidence, mortality, and costs were evaluated over a one year time horizon.
      Healthcare costs were calculated using a payer perspective and included
      vaccination program costs and direct medical expenditures from pneumococcal
      disease. RESULTS: The model predicted that routine PCV7 vaccination of infants in
      China would prevent 5,053,453 cases of pneumococcal disease and 76,714 deaths in
      a single year during a normal influenza season.The estimated incremental-cost
      effectiveness ratios were Y12,281 (US$1,900) per life-year saved and Y13,737
      (US$2,125) per quality-adjusted-life-year gained. During an influenza pandemic,
      the model estimated that routine vaccination with PCV7 would prevent 8,469,506
      cases of pneumococcal disease and 707,526 deaths, and would be cost-saving.
      CONCLUSIONS: Routine vaccination with PCV7 in China would be a cost-effective
      strategy at limiting the negative impact of influenza during a typical influenza
      season. During an influenza pandemic, the benefit of PCV7 in preventing excess
      pneumococcal morbidity and mortality renders a PCV7 vaccination program cost
      saving.

PMID- 26206276
TI  - Infants' observation of others' actions: Brief movement-specific visual
      experience primes motor representations.
AB  - Recent research suggests that infants' observation of others' reaching actions
      activates corresponding motor representations which develop with their motor
      experience. Contralateral reaching develops a few months later than ipsilateral
      reaching, and 9-month-old infants are less likely to map the observation of these
      reaches to their motor representations. The goal of the current study was to test
      whether a brief familiarization with contralateral reaching is sufficient to
      prime this less developed motor representation to increase the likelihood of its
      activation. In Experiment 1, infants were familiarized with contralateral
      reaching before they were tested in an observational version of the A-not-B
      paradigm. A significant number of infants searched incorrectly, suggesting that
      the observation of contralateral reaching primed their motor representations. In
      Experiment 2, infants were familiarized with ipsilateral reaching, which shared
      the goals but not the movements associated with the contralateral reaches
      observed during testing, and they did not show a search bias. Taken together,
      these results suggest that a brief familiarization with a movement-specific
      behaviour facilitates the direct matching of observed and executed actions. 

PMID- 26206277
TI  - Chromatin segmentation based on a probabilistic model for read counts explains a
      large portion of the epigenome.
AB  - Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is an
      increasingly common experimental approach to generate genome-wide maps of histone
      modifications and to dissect the complexity of the epigenome. Here, we propose
      EpiCSeg: a novel algorithm that combines several histone modification maps for
      the segmentation and characterization of cell-type specific epigenomic
      landscapes. By using an accurate probabilistic model for the read counts, EpiCSeg
      provides a useful annotation for a considerably larger portion of the genome,
      shows a stronger association with validation data, and yields more consistent
      predictions across replicate experiments when compared to existing methods.The
      software is available at http://github.com/lamortenera/epicseg. 

PMID- 26206278
TI  - Spermatogenesis, DNA damage and DNA repair mechanisms in male infertility.
AB  - Spermatogenesis is a complex process of proliferation and differentiation during
      male germ cell development involving mitosis, meiosis and spermiogenesis.
      Endogenous and exogenous physical, chemical and biological sources modify the
      genome of spermatozoa. The genomic integrity and stability of the sperm is
      protected by DNA repair mechanisms. In the male germline cells, DNA repair
      mechanisms include nucleotide excision repair, base excision repair, DNA mismatch
      repair, double strand break repair and post-replication repair. Defects in repair
      mechanisms cause arrest of spermatogenesis and abnormal recombination, ultimately
      resulting in male infertility. This review focuses on molecular mechanisms of the
      DNA repair pathways, DNA repair defects and male infertility. 

PMID- 26206279
TI  - Habits of cell phone usage and sperm quality - does it warrant attention?
AB  - Male infertility constitutes 30-40% of all infertility cases. Some studies have
      shown a continuous decline in semen quality since the beginning of the 20th
      century. One postulated contributing factor is radio frequency electromagnetic
      radiation emitted from cell phones. This study investigates an association
      between characteristics of cell phone usage and semen quality. Questionnaires
      accessing demographic data and characteristics of cell phone usage were completed
      by 106 men referred for semen analysis. Results were analysed according to WHO
      2010 criteria. Talking for >=1 h/day and during device charging were associated
      with higher rates of abnormal semen concentration (60.9% versus 35.7%, P < 0.04
      and 66.7% versus 35.6%, P < 0.02, respectively). Among men who reported holding
      their phones <=50 cm from the groin, a non-significantly higher rate of abnormal
      sperm concentration was found (47.1% versus 11.1%). Multivariate analysis
      revealed that talking while charging the device and smoking were risk factors for
      abnormal sperm concentration (OR = 4.13 [95% CI 1.28-13.3], P < 0.018 and OR =
      3.04 [95% CI 1.14-8.13], P < 0.027, respectively). Our findings suggest that
      certain aspects of cell phone usage may bear adverse effects on sperm
      concentration. Investigation using large-scale studies is thus needed.

PMID- 26206280
TI  - A survey of UK fertility clinics' approach to surrogacy arrangements.
AB  - This paper draws on the findings of the first survey of surrogacy arrangements in
      Human Fertilisation and Embryology Authority (HFEA) licensed fertility clinics
      since 1998. Given the complex social, ethical and legal issues involved,
      surrogacy continues to raise debate worldwide and fuel calls for increased
      domestic provision in developed countries. However, little is known about how
      recent changes have affected HFEA licensed clinics. A 24-item online survey was
      undertaken between August and October 2013, designed to improve understanding of
      recent trends and current practices associated with UK-based surrogacy, and
      consider the implications for future policy and practice in UK and cross-border
      surrogacy arrangements. The response rate was 51.4%, comprising 54 clinics.
      Quantitative data were analysed using descriptive statistics, and open-ended
      qualitative responses analysed for extending understanding. Of the participating
      clinics, 42.6% offered surrogacy (mostly gestational surrogacy). Heterosexual
      couples using gestational surrogacy were the largest group currently using
      services followed by male same-sex couples. Most clinics reported having
      encountered problems with surrogacy treatments, suggesting barriers still exist
      to expanding the UK provision of surrogacy arrangements. It is important that
      professionals are well informed about the legal implications of surrogacy and
      that clinics have consistent and appropriate operational protocols for surrogacy
      arrangements. 

PMID- 26206281
TI  - Is parental consanguinity associated with reduced ovarian reserve?
AB  - This observational study assessed whether women descending from consanguineous
      unions have reduced ovarian reserve compared with daughters of non-consanguine
      couples. Two hundred and ninety-one women (<=39 years) were treated in a tertiary
      care centre in Kuwait. Women underwent a complete anamnesis, including an
      evaluation of the possible presence of parental consanguinity, transvaginal
      ultrasound on day 2/3 of the cycle to obtain the antral follicle count (AFC),
      determination of serum concentrations of FSH, LH, oestradiol and in case of low
      ovarian reserve (AFC < 9) anti-Mullerian hormone (AMH). The median AFC of non
      consanguineous daughters was 11, while daughters from consanguineous parents
      displayed a significantly lower median AFC (7; P < 0?0001). FSH was slightly
      higher in the consanguineous patients, while LH and oestradiol concentrations did
      not vary between groups. In total, 29.9% of consanguineous patients had an AFC >=
      9, compared with 63.9% of non-consanguineous patients. Consanguineous patients
      did not exhibit an age-dependent AFC-decline and displayed reduced AFC and AMH
      concentrations. The multivariate analysis revealed female consanguinity, as well
      as surgical history in non-consanguineous women, as strong positive predictors of
      low ovarian reserve. Parental consanguinity is strongly associated with reduced
      ovarian reserve. Future studies should evaluate a possible association between
      parental consanguinity and infertility. 

PMID- 26206282
TI  - Protective effect of resveratrol against oxidative damage to ovarian reserve in
      female Sprague-Dawley rats.
AB  - An increased accumulation of intracellular levels of reactive oxygen species with
      time may play an important role in the process of ageing. The antioxidant
      properties of resveratrol are dependent upon the up-regulation of endogenous
      cellular antioxidant systems. We evaluated whether resveratrol has protective
      antioxidant effects on ovarian damage related to oxidative stress in a rat model.
      Twenty-four female rats were randomly divided into three groups and were given
      saline (group 1: control); intraperitoneal cisplatin, 4.5 mg/kg, two weekly doses
      in total (group 2); or cisplatin, 4.5 mg/kg plus intraperitoneal resveratrol 10
      mg/kg/day, 24 h before the administration of cisplatin (group 3). Serum anti
      Mullerian hormone (AMH) concentrations were significantly lower in group 2 than
      in group 3 (P < 0.01 and P = 0.04, respectively). The evaluation of the atretic
      and antral follicle counts revealed statistically significant differences between
      the groups (P = 0.04 and P < 0.01, respectively). A statistically significant
      difference was observed in the follicle count positive for AMH between the groups
      (P = 0.01). Oxidative stress plays an important role in the process of ovarian
      ageing. Because of its natural antioxidant properties, resveratrol may be an
      effective option in protecting ovarian tissue against oxidative damage.

PMID- 26206283
TI  - Live births following Karyomapping of human blastocysts: experience from clinical
      application of the method.
AB  - The clinical application of a new, widely applicable method known as Karyomapping
      to carry out a total of 55 clinical cases of preimplantation genetic diagnosis
      (PGD) for single gene disorders is reported. Conventional polymerase chain
      reaction (PCR) testing was carried out in parallel to the new method for all
      cases. Clinical application of Karyomapping in this study resulted in three live
      births and nine clinical pregnancies out of 20 cases with a transfer. All in all,
      results presented in this study indicate that Karyomapping is a highly efficient,
      accurate and robust method for PGD of single gene disorders. Karyomapping can
      offer a more comprehensive assessment of the region of interest than conventional
      PCR analysis, allowing for more embryos to receive diagnosis (99.6% versus
      96.8%), whereas its wide applicability reduces substantially the time that
      patients have to wait before starting their in vitro fertilization (IVF) cycle.
      Nonetheless, inclusion of elements of conventional PCR methodology, such as
      direct mutation detection, may be required in cases in which the gene of interest
      is in a region with reduced single nucleotide polymorphism (SNP) coverage (e.g.
      telomeric regions), when offering PGD for consanguineous couples, or in cases
      where no samples from additional family members are available. 

PMID- 26206284
TI  - System for evaluation of oxidative stress on in-vitro-produced bovine embryos.
AB  - This study proposed a quantitative evaluation of oxidative status (OS) in bovine
      embryos. Sixteen-cell stage embryos, cultured under 5% O2, were treated with
      oxidative stress inducer menadione (0, 1, 2.5 and 5 umol/l) for 24 h. Blastocyst
      rate (BLR) was recorded and expanded blastocysts were stained with
      CellROX(r)Green (CRG; OS evaluation) and evaluated under epifluorescence
      microscopy (ratio of pixel/blastomere). A significant effect of menadione was
      observed for BLR (P = 0.0039), number of blastomeres/embryo (P < 0.0001) and OS
      (P < 0.001). Strong negative correlations were found between BLR and the number
      of blastomeres with OS evaluation, demonstrating the efficacy of this analysis to
      evaluate OS levels of IVF bovine embryos. 

PMID- 26206285
TI  - Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to
      defective insulin and glucagon secretion in human type 2 diabetes.
AB  - Islet produced 5-hydroxy tryptamine (5-HT) is suggested to regulate islet hormone
      secretion in a paracrine and autocrine manner in rodents. Hitherto, no studies
      demonstrate a role for this amine in human islet function, nor is it known if 5
      HT signaling is involved in the development of beta cell dysfunction in type 2
      diabetes (T2D). To clarify this, we performed a complete transcriptional mapping
      of 5-HT receptors and processing enzymes in human islets and investigated
      differential expression of these genes in non-diabetic and T2D human islet
      donors. We show the expression of fourteen 5-HT receptors as well as processing
      enzymes involved in the biosynthesis of 5-HT at the mRNA level in human islets.
      Two 5-HT receptors (HTR1D and HTR2A) were over-expressed in T2D islet donors.
      Both receptors (5-HT1d and 5-HT2a) were localized to human alpha, beta and delta
      cells. 5-HT inhibited both insulin and glucagon secretion in non-diabetic islet
      donors. In islets isolated from T2D donors the amine significantly increased
      release of insulin in response to glucose. Our results suggest that 5-HT
      signaling participates in regulation of overall islet hormone secretion in non-
      diabetic individuals and over-expression of HTR1D and HTR2A may either contribute
      to islet dysfunction in T2D or arise as a consequence of an already dysfunctional
      islet. 

PMID- 26206286
TI  - Antimicrobial activity of human alpha-defensin 5 and its linear analogs: N
      terminal fatty acylation results in enhanced antimicrobial activity of the linear
      analogs.
AB  - Human alpha-defensin 5 (HD5) exhibits broad spectrum antimicrobial activity and
      plays an important role in mucosal immunity of the small intestine. Although
      there have been several studies, the structural requirements for activity and
      mechanism of bacterial killing is yet to be established unequivocally. In this
      study, we have investigated the antimicrobial activity of HD5 and linear analogs.
      Cysteine deletions attenuated the antibacterial activity considerably.
      Candidacidal activity was affected to a lesser extent. Fatty acid conjugated
      linear analogs showed antimicrobial activity comparable activity to HD5.
      Effective surface charge neutralization of bacteria was observed for HD5 as
      compared to the non-fatty acylated linear analogs. Our results show that HD5 and
      non-fatty acylated linear analogs enter the bacterial cytoplasm without causing
      damage to the bacterial inner membrane. Although fatty acylated peptides
      exhibited antimicrobial activity comparable to HD5, their mechanism of action
      involved permeabilization of the Escherichia coli inner membrane. HD5 and analogs
      had the ability to bind plasmid DNA. HD5 had greater binding affinity to plasmid
      DNA as compared to the analogs. The three dimensional structure of HD5 favors
      greater interaction with the bacterial cell surface and also with DNA.
      Antibacterial activity of HD5 involves entry into bacterial cytoplasm and binding
      to DNA which would result in shut down of the bacterial metabolism leading to
      cell death. We show how a moderately active linear peptide derived from the alpha
      defensin HD5 can be engineered to enhance antimicrobial activity almost
      comparable to the native peptide. 

PMID- 26206287
TI  - Vasoactive intestinal peptide (VIP) differentially affects inflammatory immune
      responses in human monocytes infected with viable Salmonella or stimulated with
      LPS.
AB  - We compared the effect of VIP on human blood monocytes infected with Salmonella
      typhimurium 4/74 or stimulated with LPS. VIP (10(-7)M) increased monocyte
      viability by 24% and 9% when cultured for 24h with 4/74 or Salmonella LPS
      (100ng/ml), respectively. Significantly increased (P<0.05) numbers of 4/74 were
      also recovered from monocytes co-cultured with VIP after 6h post-infection (pi)
      and this remained high after 24h pi. Both 4/74 and LPS increased (P<0.05) the
      concentration of TNF-alpha, IL-1beta and IL-6 measured in monocyte supernatants.
      However, LPS induced this effect more rapidly while, with the exception of IL-6,
      4/74 induced higher concentrations (P<0.05). VIP significantly decreased (P<0.05)
      TNF-alpha and IL-1beta production by 4/74-infected monocytes after 6 pi, but only
      after 24h in LPS-cultured monocytes. This trend was reversed for IL-6 production.
      However, TNF-alpha and IL-1beta production by 4/74-infected monocytes, cultured
      with VIP, still remained higher (P<0.05) than concentrations measured in
      supernatants cultured only with LPS. VIP also increased (P<0.05) production of
      anti-inflammatory IL-10 in both 4/74 and LPS cultures after 24h. We also show a
      differential effect of VIP on the expression of TNFalpha and IL-6 receptors,
      since VIP was only able to decreased expression in LPS-stimulated monocytes but
      not in 4/74-infected monocytes. In conclusion, we show a differential effect of
      VIP on human monocytes infected with virulent Salmonella or stimulated with LPS.
      Our study suggests that the use of VIP in bacteraemia and/or sepsis may be
      limited to an adjunctive therapy to antibiotic treatment. 

PMID- 26206288
TI  - Nonsulfated cholecystokinins in the small intestine of pigs and rats.
AB  - Cholecystokinin (CCK) is a gut hormone that acts via two receptors. The CCKA
      receptor requires the tyrosyl residue in the C-terminal bioactive site of CCK to
      be O-sulfated, whereas, the CCKB-receptor binds irrespective of sulfation.
      Consequently, unsulfated CCK peptides - if present - may constitute a hormone
      system that acts only through the CCKB-receptor. Therefore, we have now examined
      whether, CCK peptides occur in nonsulfated form in the small intestine of pigs
      and rats. The concentrations of sulfated and nonsulfated CCK were measured by
      RIAs, one specific for sulfated CCKs and a new two-step assay specific for
      nonsulfated CCK. For further characterization, the intestinal extracts were
      subjected to size- and ion exchange-chromatography. The intestinal concentrations
      of sulfated and nonsulfated CCK were highest in the duodenum and the proximal
      part of jejunum both in the pig and the rat. The porcine duodenal mucosa
      contained 193+/-84pmol/g sulfated CCK and 31+/-10pmol/g nonsulfated CCK, and the
      upper rat intestine 70+/-19pmol/g and 8+/-2pmol/g, respectively. The degree of
      sulfation correlated with the endoproteolytic proCCK processing. Thus, 38% of
      porcine CCK-58 was unsulfated, whereas, only 12% of CCK-8 was unsulfated. The
      results show that a substantial part of intestinal CCK peptides in rats and pigs
      are not sulfated, and that the longer peptides (CCK-58 and CCK-33) are less
      sulfated than the shorter (CCK-22 and CCK-8). Hence, the results demonstrate that
      proCCK in the gut is processed both to sulfated and unsulfated alpha-amidated
      peptides of which the latter are assumed to act via the CCKB-receptor. 

PMID- 26206289
TI  - Proinsulin multi-peptide immunotherapy induces antigen-specific regulatory T
      cells and limits autoimmunity in a humanized model.
AB  - Peptide immunotherapy (PIT) is a targeted therapeutic approach, involving
      administration of disease-associated peptides, with the aim of restoring antigen
      specific immunological tolerance without generalized immunosuppression. In type 1
      diabetes, proinsulin is a primary antigen targeted by the autoimmune response,
      and is therefore a strong candidate for exploitation via PIT in this setting. To
      elucidate the optimal conditions for proinsulin-based PIT and explore mechanisms
      of action, we developed a preclinical model of proinsulin autoimmunity in a
      humanized HLA-DRB1*0401 transgenic HLA-DR4 Tg mouse. Once proinsulin-specific
      tolerance is broken, HLA-DR4 Tg mice develop autoinflammatory responses,
      including proinsulin-specific T cell proliferation, interferon (IFN)-gamma and
      autoantibody production. These are preventable and quenchable by pre- and post
      induction treatment, respectively, using intradermal proinsulin-PIT injections.
      Intradermal proinsulin-PIT enhances proliferation of regulatory [forkhead box
      protein 3 (FoxP3(+))CD25(high) ] CD4 T cells, including those capable of
      proinsulin-specific regulation, suggesting this as its main mode of action. In
      contrast, peptide delivered intradermally on the surface of vitamin D3-modulated
      (tolerogenic) dendritic cells, controls autoimmunity in association with
      proinsulin-specific IL-10 production, but no change in regulatory CD4 T cells.
      These studies define a humanized, translational model for in vivo optimization of
      PIT to control autoimmunity in type 1 diabetes and indicate that dominant
      mechanisms of action differ according to mode of peptide delivery.

PMID- 26206290
TI  - Comparison of the effect of two different bone-targeted radiofrequency ablation
      (RFA) systems alone and in combination with percutaneous vertebroplasty (PVP) on
      the biomechanical stability of the metastatic spine.
AB  - INTRODUCTION: Radiofrequency ablation (RFA) and percutaneous vertebroplasty (PVP)
      are used independently and in combination to treat metastatically involved
      vertebrae with the aim of relieving pain, reducing tumour burden and providing
      bony mechanical stabilization. PURPOSE: The aim of this work was to characterize
      the effect of two bone-targeted RFA devices, alone and in combination with PVP,
      to improve strength and mechanical stability in vertebrae with osteolytic
      metastatic disease. METHODS: Simulated spinal metastases (n = 12) were treated
      with one of two bone-targeted RFA devices (bipolar cooled or bone coil RF
      electrodes), followed by PVP. Under axial compressive loading, spinal canal
      narrowing was measured in the intact specimen, after tumour simulation, post-RFA
      and post-PVP. RESULTS: RFA alone resulted in successful tumour shrinkage and
      cavitation, but further increased canal narrowing under loading. RFA combined
      with PVP significantly reduced posterior wall stability in samples where
      sufficient tumour shrinkage and cavitation were coupled with a pattern of cement
      deposition which extended to posterior vertebral body. CONCLUSIONS: RFA combined
      with cement deposition in the posterior vertebral body demonstrates significantly
      more stable vertebrae under axial loading.

PMID- 26206291
TI  - Reviewer's comment to Letter to the Editor of Jingming Lin et al. concerning
      "Comparison of unilateral versus bilateral pedicle screw fixation in lumbar
      interbody fusion: a meta-analysis" (by W. Ding et al. (2014) Eur Spine J
      23(2):395-403): and authors' reply of Wenbin Ding et al.

PMID- 26206292
TI  - Photographic measurement of head and cervical posture when viewing mobile phone:
      a pilot study.
AB  - PURPOSE: With the dramatic growth of mobile phone usage, concerns have been
      raised with regard to the adverse health effects of mobile phone on spinal
      posture. The aim of this study was to determine the head and cervical postures by
      photogrammetry when viewing the mobile phone screen, compared with those in
      neutral standing posture. METHODS: A total of 186 subjects (81 females and 105
      males) aged from 17 to 31 years old participated in this study. Subjects were
      instructed to stand neutrally and using mobile phone as in daily life. Using a
      photographic method, the sagittal head and cervical postures were assessed by
      head tilt angle, neck tilt angle, forward head shift and gaze angle. RESULTS: The
      photographic method showed a high intra-rater and inter-rater reliability in
      measuring the sagittal posture of cervical spine and gaze angle (ICCs ranged from
      0.80 to 0.99). When looking at mobile phone, the head tilt angle significantly
      increased (from 74.55 degrees  to 95.22 degrees , p = 0.000) and the neck angle
      decreased (from 54.68 degrees  to 38.77 degrees , p = 0.000). The forward head
      posture was also confirmed by the significantly increased head shift (from 10.90
      to 13.85 cm, p = 0.000). The posture assumed in mobile phone use was
      significantly correlated with neutral posture (p < 0.05). Males displayed a more
      forward head posture than females (p < 0.05). The head tilt angle was positively
      correlated with the gaze angle (r = 0.616, p = 0.000), while the neck tilt angle
      was negatively correlated with the gaze angle (r = -0.628, p = 0.000).
      CONCLUSIONS: Photogrammetry is a reliable, quantitative method to evaluate the
      head and cervical posture during mobile phone use. Compared to neutral standing,
      subjects display a more forward head posture when viewing the mobile phone
      screen, which is correlated with neutral posture, gaze angle and gender. Future
      studies will be needed to investigate a dose-response relationship between mobile
      phone use and assumed posture.

PMID- 26206293
TI  - Intervertebral disc lesions: visualisation with ultra-high field MRI at 11.7 T.
AB  - PURPOSE: Tears and fissures in the intervertebral disc are probably influencing
      spinal stability. Discography investigations with the aim of fissure detection
      have been criticised and are discouraged. Therefore, alternative imaging methods,
      such as MRI, must be investigated. METHODS: A custom-made device was used to
      insert six needles with different diameters (0.3-2.2 mm/30-14 G) into the annulus
      of six bovine tail discs (Cy2-Cy3). Directly after removal of the needles, the
      discs were scanned in an 11.7 T MRI (Res.: 0.059 * 0.059 * 0.625 mm(3), tscan: 31
      min), in a 3 T MRI with a clinical and additionally with two experimental
      protocols (exp_HR: Res.: 0.3 mm(3), tscan: 97 min/exp_LR: Res.: 0.5 mm(3), tscan:
      13.4 min). The obtained images were analysed for lesion volume and lesion length
      using a 3D-reconstruction software. RESULTS: At 11.7 T, all lesions were visible
      along with the lamellar structure of the annulus. In the clinical 3 T images, no
      lesions were visible at all. The 3 T experimental protocols revealed 4 (exp_HR)
      and 2 (exp_LR) of the 6 lesions. The reconstructed lesions did not have an ideal
      cylindrical shape. The measured volumes of the lesions ranged from 0.7 to 13.9
      mm(3) (11.7 T), 0.1-11.4 mm(3) (exp_HR) and 0.0-12.4 mm(3) (exp_LR) and
      correlated, but were smaller than the corresponding needle size. The lengths of
      all needle lesions ranged from 2.9 to 12.3 mm (11.7 T), 0.8-9.7 mm (exp_HR) and
      0.0-9.7 mm (exp_LR). CONCLUSIONS: Ultra-high field MRI at 11.7 T is a non
      invasive tool to directly visualise annular lesions in vitro, while a 3 T MRI,
      even with experimental protocols and longer scanning times, demonstrates limited
      ability. In vivo, it is problematic with the clinical systems available today.

PMID- 26206294
TI  - Adding quality to day centre activities for people with psychiatric disabilities:
      Staff perceptions of an intervention.
AB  - AIM: To evaluate an intervention aimed at enriching day centres for people with
      psychiatric disabilities by exploring staff experiences from developing and
      implementing the intervention. METHOD: Each staff group developed a tailor-made
      intervention plan, following a manual, for how to enrich the day centre. They
      received supervision and support from the research team. The study was based on
      focus-group interviews with a total of 13 staff members at four day centres.
      Narrative analysis with a thematic approach was used. A first round resulted in
      one narrative per centre. These centre-specific narratives were then integrated
      into a common narrative that covered all the data. RESULTS: A core theme emerged:
      User involvement permeated the implementation process and created empowerment. It
      embraced four themes forming a timeline: "Mix of excitement, worries and hope",
      "Confirmation and development through dialogue, feedback and guidance", "The art
      of integrating new activities and strategies with the old", and "Empowerment
      engendered future aspirations". CONCLUSION: The users' involvement and
      empowerment were central for the staff in accomplishing the desired changes in
      services, as were their own reflections and learning. A possible factor that may
      have contributed to the positive outcomes was that those who were central in
      developing the plan were the same as those who implemented it.

PMID- 26206295
TI  - The Chinese herb-derived Sparstolonin B suppresses HIV-1 transcription.
AB  - BACKGROUND: The Chines herb derived Sparstolonin B, (SsnB), is a recently
      identified natural compound that selectively blocks TLR2- and TLR4-mediated
      inflammatory signaling. But it is unknown whether this compound has any effect on
      HIV infection. FINDINGS: We found that SsnB treatment blocked HIV-1 transcription
      via a novel mechanism that requires the TAR region. Treatment of human T cell
      lines or peripheral blood mononuclear cells with SsnB at 1 MUM significantly
      inhibited HIV production. Lastly, SsnB was able to inhibit HIV in synergy with
      AZT. CONCLUSIONS: These data suggest that SsnB is a novel natural compound that
      inhibits HIV-1 transcription and may be a new drug in the treatment of HIV
      infection.

PMID- 26206296
TI  - Computer-aided scaffold hopping to identify a novel series of casein kinase 1
      delta (CK1d) inhibitors for amyotrophic lateral sclerosis.
AB  - In this study as the first attempt; comparative molecular field analysis (CoMFA),
      comparative molecular similarity indices analysis (CoMSIA) and AutoGPA-based 3D
      QSAR methods were applied on a set of 47 recently reported Ck1d inhibitors, in
      order to gain an insight into the structural requirements which providing
      guidelines for the design of next generation compounds with enhanced bioactivity.
      The results of 3D-QSAR analyses indicated that hydrophobic and negatively charged
      groups at 6th position of benzothiazole ring and positively charged and bulky
      groups at ortho position of phenyl ring are favorable for high activity.
      Moreover, molecular docking studies with GOLD protocol revealed that this
      chemical series has two different orientations in CK1d active site: orientation
      1, in which the benzothiazole ring of the compounds is the closet to the
      hydrophobic area created by Ile23 and 37, Ala36 Lys 38, Met80, 82 and Val81, and
      orientation 2, in which the benzene ring of the compounds is directed toward the
      hydrophobic center. Molecular docking result of the riluzole, the only drug
      approved by FDA for amyotrophic lateral sclerosis (ALS), indicated that the
      orientation 2 is preferred due to the presence of OCF3 group in R(1) situation at
      6th position of benzothiazole ring, while with replacement of OCF3 group by CF3,
      the orientation 1 is observed. At the end, to find similar analogs by virtual
      screening, a two-stage approach: pharmacophore-based screening using generated
      AutoGPA-based 3D-QSAR model followed by structure-based virtual screening using
      molecular docking was employed. Visual inspection of the docking results of
      virtually obtained hits revealed two different binding orientations, in which
      compounds with high GOLD fitness scores produced binding modes, which were the
      same as the one observed in compounds with orientation 1, whereas the binding
      modes of the structures with low GOLD fitness scores were in agreement with
      orientation 2. Further, the drug-like properties of the obtained seven hits with
      the highest GOLD scores were investigated as a tool to optimize the selection of
      the most suitable candidates for drug development. 

PMID- 26206297
TI  - A novel approach to arthritis treatment based on resveratrol and curcumin co
      encapsulated in lipid-core nanocapsules: In vivo studies.
AB  - Resveratrol and curcumin are two natural polyphenols extensively used due to
      their remarkable anti-inflammatory activity. The present work presents an
      inedited study of the in vivo antioedematogenic activity of these polyphenols co
      encapsulated in lipid-core nanocapsules on Complete Freund's adjuvant (CFA)
      induced arthritis in rats. Lipid-core nanocapsules were prepared by interfacial
      deposition of preformed polymer. Animals received a single subplantar injection
      of CFA in the right paw. Fourteen days after arthritis induction, they were
      treated with resveratrol, curcumin, or both in solution or loaded in lipid-core
      nanocapsules (1.75 mg/kg/twice daily, i.p.), for 8 days. At the doses used, the
      polyphenols in solution were not able to decrease paw oedema. However,
      nanoencapsulation improved the antioedematogenic activity of polyphenols at the
      same doses. In addition, the treatment with co-encapsulated polyphenols showed
      the most pronounced effects, where an inhibition of 37-55% was observed between
      day 16 and 22 after arthritis induction. This treatment minimized most of the
      histological changes observed, like fibrosis in synovial tissue, cartilage and
      bone loss. In addition, unlike conventionally arthritis treatment, resveratrol
      and curcumin co-encapsulated in lipid-core nanocapsules did not alter important
      hepatic biochemical markers (ALP, AST, and ALT). In conclusion, the strategy of
      co-encapsulating resveratrol and curcumin in lipid-core nanocapsules improves
      their efficacy as oedematogenic agents, with no evidence of hepatotoxic effects.
      This is a promising strategy for the development of new schemes for treatment of
      chronic inflammation diseases, like arthritis.

PMID- 26206298
TI  - Environmental enrichment and working memory tasks decrease hippocampal cell
      proliferation after wheel running--A role for the prefrontal cortex in
      hippocampal plasticity?
AB  - Despite an increasing amount of evidence about the regulation of adult
      hippocampal neurogenesis on the local level, less attention has been paid to its
      systemic embedding in wider brain circuits. The aim of the present study was to
      obtain evidence for a potential role of the prefrontal cortex in the regulation
      of adult hippocampal neurogenesis. We hypothesised that activation of the
      prefrontal cortex by environmental enrichment or a working-memory task would
      decrease previously enhanced cell proliferation rates. Wheel running was applied
      as a common stimulator of cell proliferation in CD1 mice reared under deprivation
      of natural environmental stimulation. Next, the animals were assigned to four
      groups for different treatments in the following three days: housing under
      continued deprivation, environmental enrichment, a spatial-delayed alternation
      task in an automated T-maze that activates the prefrontal cortex by working
      memory requirements or a control task in the automated T-maze differing only in
      the single parameter working-memory-associated delay. Both the environmental
      enrichment and spatial-delayed alternation tasks decreased cell proliferation
      rates in the dentate gyrus compared to deprived housing and the control task in
      the T-maze. As the control animals underwent the same procedures and stressors
      and differed only in the single parameter working-memory-associated delay, the
      working-memory requirement seems to be the crucial factor for decreasing cell
      proliferation rates. Taken together, these results suggest that the prefrontal
      cortex may play a role in the regulation of hippocampal cell proliferation. 

PMID- 26206299
TI  - Neurite outgrowth promoting effect of 17-beta estradiol is mediated through
      estrogen receptor alpha in an olfactory epithelium culture.
AB  - Olfactory deficits are observed early in the course of chronic neurological
      disorders including Alzheimer's disease (AD). Estrogen treatment in post
      menopausal women reduced the incidence of olfactory dysfunction, raising the
      possibility that estrogen treatment can cure olfactory deficits in preclinical
      stages of AD. In this study, we examined the estradiol's effects on neurite
      outgrowth in explant cultures of mouse olfactory epithelium (OE). We found that
      neurons in OE cultures treated with 100 pM 17-beta estradiol (estradiol) had
      significantly longer neurite outgrowth than cultures treated with ethanol alone
      (vehicle). The OE neurons expressed estrogen receptors alpha (ERalpha) and ER
      beta (ERbeta). Estrogen treatment upregulated both ERalpha and ERbeta expression
      in OE culture. Treatment of OE cultures with propyl pyrazole triol (PPT), a
      selective agonist for ERalpha increased neurite outgrowth to comparable extent as
      estradiol treatment. In contrast, 2,3-bis-4-hydroxyphenyl (DPN), a specific
      agonist for ERbeta, had no effect on neurite outgrowth. Furthermore, estradiol
      treatment increased neurite outgrowth in OE cultures derived from ERbeta
      deficient/knockout mice and wild-type littermates, but not in ERalpha
      deficient/knockout mice. These data suggest that ERalpha mediates the neurite
      outgrowth promoting effects of estradiol in OE cultures. We propose that
      olfactory dysfunction in chronic neurological disorders, where estrogen
      deficiency is a risk factor, is an indicator of compromised axonal regeneration
      of olfactory sensory neurons.

PMID- 26206300
TI  - Differential parietal and temporal contributions to music perception in
      improvising and score-dependent musicians, an fMRI study.
AB  - Using fMRI, cerebral activations were studied in 24 classically-trained keyboard
      performers and 12 musically unskilled control subjects. Two groups of musicians
      were recruited: improvising (n=12) and score-dependent (non-improvising)
      musicians (n=12). While listening to both familiar and unfamiliar music, subjects
      either (covertly) appraised the presented music performance or imagined they were
      playing the music themselves. We hypothesized that improvising musicians would
      exhibit enhanced efficiency of audiomotor transformation reflected by stronger
      ventral premotor activation. Statistical Parametric Mapping revealed that, while
      virtually 'playing along' with the music, improvising musicians exhibited
      activation of a right-hemisphere distribution of cerebral areas including
      posterior-superior parietal and dorsal premotor cortex. Involvement of these
      right-hemisphere dorsal stream areas suggests that improvising musicians
      recruited an amodal spatial processing system subserving pitch-to-space
      transformations to facilitate their virtual motor performance. Score-dependent
      musicians recruited a primarily left-hemisphere pattern of motor areas together
      with the posterior part of the right superior temporal sulcus, suggesting a
      relationship between aural discrimination and symbolic representation.
      Activations in bilateral auditory cortex were significantly larger for
      improvising musicians than for score-dependent musicians, suggesting enhanced top
      down effects on aural perception. Our results suggest that learning to play a
      music instrument primarily from notation predisposes musicians toward aural
      identification and discrimination, while learning by improvisation involves audio
      spatial-motor transformations, not only during performance, but also perception. 

PMID- 26206301
TI  - Effects of production training and perception training on lexical tone perception
      -A behavioral and ERP study.
AB  - The present study recorded both behavioral data and event-related brain
      potentials to examine the effectiveness of a perception-only training and a
      perception-plus-production training procedure on the intentional and
      unintentional perception of lexical tone by native English listeners. In the
      behavioral task, both the perception-only and the perception-plus-production
      groups improved on the tone discrimination abilities after the training session.
      Moreover, the participants in both groups generalized the improvements gained
      through the trained stimuli to the untrained stimuli. In the ERP task, the
      Mismatch Negativity was smaller in the post-training task than in the pre
      training task. However, the two training groups did not differ in tone processing
      at the intentional or unintentional level after training. These results suggest
      that the employment of the motor system does not specifically benefit the tone
      perceptual skills. Furthermore, the present study investigated whether some tone
      pairs are more easily confused than others by native English listeners, and
      whether the order of tone presentation influences non-native tone discrimination.
      In the behavioral task, Tone2-Tone1 (rising-level) and Tone2-Tone4 (rising
      falling) were the most difficult tone pairs, while Tone1-Tone2 and Tone4-Tone2
      were the easiest tone pairs, even though they involved the same tone contrasts
      respectively. In the ERP task, the native English listeners had good
      discrimination when Tone2 and Tone4 were embedded in strings of Tone1, while poor
      discrimination when Tone1 was inserted in the context of Tone2 or Tone4. These
      asymmetries in tone perception might be attributed to the interference of native
      intonation system and can be altered by training.

PMID- 26206302
TI  - Pre- and postnatal bisphenol A treatment does not alter the number of tyrosine
      hydroxylase-positive cells in the anteroventral periventricular nucleus (AVPV) of
      weanling male and female rats.
AB  - Exposure to Bisphenol A (BPA) may interfere with brain sexual differentiation.
      Altered numbers of tyrosine hydroxylase (TH) cells in the rodent anteroventral
      periventricular nucleus (AVPV) after developmental BPA treatment have been
      reported; however, definitive conclusions are lacking. The current study
      incorporated many of the guidelines suggested for endocrine disrupter research.
      Specifically, ethinyl estradiol (EE2) served as a reference estrogen, exogenous
      environmental estrogen exposure was controlled, BPA was administered orally, and
      subjects consumed a low phytoestrogen diet. Here, on gestational days 6-21,
      Sprague-Dawley rats (10-15/group) were gavaged with 2.5 or 25.0 ug BPA/kg/day or
      5.0 or 10.0 ug EE2/kg/day or the vehicle (5 ml of 0.3% aqueous
      carboxymethylcellulose/kg/day). A naive control group was weighed and restrained,
      but not gavaged. Beginning on postnatal day (PND) 1 and continuing until PND 21,
      the 4 pups/sex/litter were orally treated with the same dose their dam had
      received. On PND 21, 1/sex/litter was perfused and the brain removed. TH
      immunoreactivity (TH-ir) was counted in 8 images/pup by a technician blind to
      treatment status. ANOVA results indicated significantly higher TH-ir cells/mm(2)
      in females (main effect of sex: p<0.01); however, there was no significant effect
      of treatment or a significant interaction of treatment with sex. In a separate
      untreated group of PND 21 Sprague-Dawley pups, AVPV volume was quantified and no
      significant sexual dimorphism was apparent. Similar to our reported results of
      behavioral assessments, the BPA treatment paradigm used here (2.5 or 25.0 ug
      BPA/kg/day administered orally) does not appear to cause significant alterations
      in AVPV TH-ir.

PMID- 26206303
TI  - A skull base air fistula secondary to ventriculoperitoneal shunt siphoning.

PMID- 26206304
TI  - TEtranscripts: a package for including transposable elements in differential
      expression analysis of RNA-seq datasets.
AB  - MOTIVATION: Most RNA-seq data analysis software packages are not designed to
      handle the complexities involved in properly apportioning short sequencing reads
      to highly repetitive regions of the genome. These regions are often occupied by
      transposable elements (TEs), which make up between 20 and 80% of eukaryotic
      genomes. They can contribute a substantial portion of transcriptomic and genomic
      sequence reads, but are typically ignored in most analyses. RESULTS: Here, we
      present a method and software package for including both gene- and TE-associated
      ambiguously mapped reads in differential expression analysis. Our method shows
      improved recovery of TE transcripts over other published expression analysis
      methods, in both synthetic data and qPCR/NanoString-validated published datasets.
      AVAILABILITY AND IMPLEMENTATION: The source code, associated GTF files for TE
      annotation, and testing data are freely available at
      http://hammelllab.labsites.cshl.edu/software. CONTACT: mhammell@cshl.edu.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 26206306
TI  - High-order neural networks and kernel methods for peptide-MHC binding prediction.
AB  - MOTIVATION: Effective computational methods for peptide-protein binding
      prediction can greatly help clinical peptide vaccine search and design. However,
      previous computational methods fail to capture key nonlinear high-order
      dependencies between different amino acid positions. As a result, they often
      produce low-quality rankings of strong binding peptides. To solve this problem,
      we propose nonlinear high-order machine learning methods including high-order
      neural networks (HONNs) with possible deep extensions and high-order kernel
      support vector machines to predict major histocompatibility complex-peptide
      binding. RESULTS: The proposed high-order methods improve quality of binding
      predictions over other prediction methods. With the proposed methods, a
      significant gain of up to 25-40% is observed on the benchmark and reference
      peptide datasets and tasks. In addition, for the first time, our experiments show
      that pre-training with high-order semi-restricted Boltzmann machines
      significantly improves the performance of feed-forward HONNs. Moreover, our
      experiments show that the proposed shallow HONN outperform the popular pre
      trained deep neural network on most tasks, which demonstrates the effectiveness
      of modelling high-order feature interactions for predicting major
      histocompatibility complex-peptide binding. AVAILABILITY AND IMPLEMENTATION:
      There is no associated distributable software. CONTACT: renqiang@nec-labs.com or
      mark.gerstein@yale.edu SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 26206305
TI  - Identifying kinase dependency in cancer cells by integrating high-throughput drug
      screening and kinase inhibition data.
AB  - MOTIVATION: Targeted kinase inhibitors have dramatically improved cancer
      treatment, but kinase dependency for an individual patient or cancer cell can be
      challenging to predict. Kinase dependency does not always correspond with gene
      expression and mutation status. High-throughput drug screens are powerful tools
      for determining kinase dependency, but drug polypharmacology can make results
      difficult to interpret. RESULTS: We developed Kinase Addiction Ranker (KAR), an
      algorithm that integrates high-throughput drug screening data, comprehensive
      kinase inhibition data and gene expression profiles to identify kinase dependency
      in cancer cells. We applied KAR to predict kinase dependency of 21 lung cancer
      cell lines and 151 leukemia patient samples using published datasets. We
      experimentally validated KAR predictions of FGFR and MTOR dependence in lung
      cancer cell line H1581, showing synergistic reduction in proliferation after
      combining ponatinib and AZD8055. AVAILABILITY AND IMPLEMENTATION: KAR can be
      downloaded as a Python function or a MATLAB script along with example inputs and
      outputs at: http://tanlab.ucdenver.edu/KAR/. CONTACT: aikchoon.tan@ucdenver.edu.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 26206307
TI  - Statistical models for RNA-seq data derived from a two-condition 48-replicate
      experiment.
AB  - MOTIVATION: High-throughput RNA sequencing (RNA-seq) is now the standard method
      to determine differential gene expression. Identifying differentially expressed
      genes crucially depends on estimates of read-count variability. These estimates
      are typically based on statistical models such as the negative binomial
      distribution, which is employed by the tools edgeR, DESeq and cuffdiff. Until
      now, the validity of these models has usually been tested on either low-replicate
      RNA-seq data or simulations. RESULTS: A 48-replicate RNA-seq experiment in yeast
      was performed and data tested against theoretical models. The observed gene read
      counts were consistent with both log-normal and negative binomial distributions,
      while the mean-variance relation followed the line of constant dispersion
      parameter of ~0.01. The high-replicate data also allowed for strict quality
      control and screening of 'bad' replicates, which can drastically affect the gene
      read-count distribution. AVAILABILITY AND IMPLEMENTATION: RNA-seq data have been
      submitted to ENA archive with project ID PRJEB5348. CONTACT:
      g.j.barton@dundee.ac.uk.

PMID- 26206308
TI  - Comparison of Therapeutic Effect of Recombinant Tissue Plasminogen Activator by
      Treatment Time after Onset of Acute Ischemic Stroke.
AB  - We aimed to compare the therapeutic effect of recombinant tissue plasminogen
      activator (rt-PA) administered at different time windows within the first 6 hours
      after onset of acute ischemic stroke (AIS). A retrospective analysis was
      performed of data collected from 194 patients who received rt-PA thrombolysis
      within 4.5 hours after AIS onset and from 29 patients who received rt-PA
      thrombolysis between 4.5-6 hours after AIS onset. The National Institutes of
      Health Stroke Scale (NIHSS) scores were statistically decreased in both groups (P
      < 0.05) at 24 hours and 7 days after onset. There was no statistical difference
      in the modified Rankin score or mortality at day 90 after treatment between the
      two groups (P > 0.05). In conclusion, AIS patients who received rt-PA treatment
      between 4.5-6 hours after onset were similar in therapeutic efficacy to those who
      received rt-PA within 4.5 hours after onset. Our results suggest that intravenous
      thrombolytic therapy for AIS within 4.5-6 hours after onset is effective and
      safe. 

PMID- 26206309
TI  - Incidental head and neck findings on 18F-fluoro-deoxy-glucose positron emission
      tomography computed tomography.
AB  - OBJECTIVE: The overlapping risk factors for lung and head and neck cancer present
      a definite risk of synchronous malignant pathology. This is the first study to
      specifically review incidental positron emission tomography computed tomography
      findings in the head and neck region in lung carcinoma patients. METHODS: A
      retrospective review was performed of all lung cancer patients who underwent
      positron emission tomography computed tomography imaging over a five-year period
      (January 2008 - December 2012), identified from the Liverpool thoracic
      multidisciplinary team database. RESULTS: Six hundred and nine patients underwent
      positron emission tomography computed tomography imaging over this period. In 76
      (12.5 per cent) scans, incidental regions of avid 18F-fluoro-deoxy-glucose uptake
      were reported in the head and neck region. In the 28 patients who were fully
      investigated, there were 4 incidental findings of malignancy. CONCLUSION: In lung
      cancer patients undergoing investigative positron emission tomography computed
      tomography scanning, a significant number will also present with areas of
      clinically significant 18F-fluoro-deoxy-glucose uptake in the head and neck
      region. Of these, at least 5 per cent may have an undiagnosed malignancy.

PMID- 26206311
TI  - Medium-Term Effectiveness of a Comprehensive Internet-Based and Patient-Specific
      Telerehabilitation Program With Text Messaging Support for Cardiac Patients:
      Randomized Controlled Trial.
AB  - BACKGROUND: Cardiac telerehabilitation has been introduced as an adjunct or
      alternative to conventional center-based cardiac rehabilitation to increase its
      long-term effectiveness. However, before large-scale implementation and
      reimbursement in current health care systems is possible, well-designed studies
      on the effectiveness of this new additional treatment strategy are needed.
      OBJECTIVE: The aim of this trial was to assess the medium-term effectiveness of
      an Internet-based, comprehensive, and patient-tailored telerehabilitation program
      with short message service (SMS) texting support for cardiac patients. METHODS:
      This multicenter randomized controlled trial consisted of 140 cardiac
      rehabilitation patients randomized (1:1) to a 24-week telerehabilitation program
      in combination with conventional cardiac rehabilitation (intervention group;
      n=70) or to conventional cardiac rehabilitation alone (control group; n=70). In
      the telerehabilitation program, initiated 6 weeks after the start of ambulatory
      rehabilitation, patients were stimulated to increase physical activity levels.
      Based on registered activity data, they received semiautomatic telecoaching via
      email and SMS text message encouraging them to gradually achieve predefined
      exercise training goals. Patient-specific dietary and/or smoking cessation advice
      was also provided as part of the telecoaching. The primary endpoint was peak
      aerobic capacity (VO2 peak). Secondary endpoints included accelerometer-recorded
      daily step counts, self-assessed physical activities by International Physical
      Activity Questionnaire (IPAQ), and health-related quality of life (HRQL) assessed
      by the HeartQol questionnaire at baseline and at 6 and 24 weeks. RESULTS: Mean
      VO2 peak increased significantly in intervention group patients (n=69) from
      baseline (mean 22.46, SD 0.78 mL/[min*kg]) to 24 weeks (mean 24.46, SD 1.00
      mL/[min*kg], P<.01) versus control group patients (n=70), who did not change
      significantly (baseline: mean 22.72, SD 0.74 mL/[min*kg]; 24 weeks: mean 22.15,
      SD 0.77 mL/[min*kg], P=.09). Between-group analysis of aerobic capacity confirmed
      a significant difference between the intervention group and control group in
      favor of the intervention group (P<.001). At 24 weeks, self-reported physical
      activity improved more in the intervention group compared to the control group
      (P=.01) as did the global HRQL score (P=.01). CONCLUSIONS: This study showed that
      an additional 6-month patient-specific, comprehensive telerehabilitation program
      can lead to a bigger improvement in both physical fitness (VO2 peak) and
      associated HRQL compared to center-based cardiac rehabilitation alone. These
      results are supportive in view of possible future implementation in standard
      cardiac care.

PMID- 26206312
TI  - Challenges in SN38 drug delivery: current success and future directions.
AB  - INTRODUCTION: Clinical use of SN38 is limited by its poor aqueous solubility and
      hydrolysis of the lactone ring at pH > 6 to inactive carboxylate form. A variety
      of drug delivery systems have been developed to improve the solubility and
      stability of SN38, and reduce its toxicity. A few noteworthy formulations with
      some success in initial phases of clinical trials are reported. AREAS COVERED:
      This work aims to provide a comprehensive review on the various techniques and
      strategies employed (physical, chemical and biological methods) to improve
      physicochemical properties and to deliver the drug efficiently to the cancer
      cells. Physical methods such as nanoparticle encapsulation, cyclodextrin
      complexation; chemical methods such as prodrugs, polymer-, albumin- and
      immunoconjugates; and enzyme activated prodrug therapy are discussed. EXPERT
      OPINION: The challenges in SN38 drug delivery may be overcome by two ways:
      ensuring multiple layers of protection against degradation and slow but sustained
      release of therapeutically effective drug concentrations. It may also be achieved
      by preparing a polymer-drug conjugate and further encapsulating the conjugate in
      suitable carrier system; tumor-targeted SN38 delivery by using immunoconjugates,
      enzyme-activated prodrug therapy and antibody-directed nanoparticle delivery.
      However, selection of a suitable ligand for tumor targeting and use of safe and
      biocompatible nanoparticle systems play an important role in realizing this goal.

PMID- 26206313
TI  - Opposing roles of conventional and novel PKC isoforms in Hippo-YAP pathway
      regulation.

PMID- 26206314
TI  - Crystal structure of the Ego1-Ego2-Ego3 complex and its role in promoting Rag
      GTPase-dependent TORC1 signaling.
AB  - The target of rapamycin complex 1 (TORC1) integrates various hormonal and
      nutrient signals to regulate cell growth, proliferation, and differentiation.
      Amino acid-dependent activation of TORC1 is mediated via the yeast EGO complex
      (EGOC) consisting of Gtr1, Gtr2, Ego1, and Ego3. Here, we identify the previously
      uncharacterized Ycr075w-a/Ego2 protein as an additional EGOC component that is
      required for the integrity and localization of the heterodimeric Gtr1-Gtr2
      GTPases, equivalent to mammalian Rag GTPases. We also report the crystal
      structure of the Ego1-Ego2-Ego3 ternary complex (EGO-TC) at 2.4 A resolution, in
      which Ego2 and Ego3 form a heterodimer flanked along one side by Ego1. Structural
      data also reveal the structural conservation of protein components between the
      yeast EGO-TC and the human Ragulator, which acts as a GEF for Rag GTPases.
      Interestingly, however, artificial tethering of Gtr1-Gtr2 to the vacuolar
      membrane is sufficient to activate TORC1 in response to amino acids even in the
      absence of the EGO-TC. Our structural and functional data therefore support a
      model in which the EGO-TC acts as a scaffold for Rag GTPases in TORC1 signaling. 

PMID- 26206315
TI  - Dynamic tubulation of mitochondria drives mitochondrial network formation.
AB  - Mitochondria form networks. Formation of mitochondrial networks is important for
      maintaining mitochondrial DNA integrity and interchanging mitochondrial material,
      whereas disruption of the mitochondrial network affects mitochondrial functions.
      According to the current view, mitochondrial networks are formed by fusion of
      individual mitochondria. Here, we report a new mechanism for formation of
      mitochondrial networks through KIF5B-mediated dynamic tubulation of mitochondria.
      We found that KIF5B pulls thin, highly dynamic tubules out of mitochondria.
      Fusion of these dynamic tubules, which is mediated by mitofusins, gives rise to
      the mitochondrial network. We further demonstrated that dynamic tubulation and
      fusion is sufficient for mitochondrial network formation, by reconstituting
      mitochondrial networks in vitro using purified fusion-competent mitochondria,
      recombinant KIF5B, and polymerized microtubules. Interestingly, KIF5B only
      controls network formation in the peripheral zone of the cell, indicating that
      the mitochondrial network is divided into subzones, which may be constructed by
      different mechanisms. Our data not only uncover an essential mechanism for
      mitochondrial network formation, but also reveal that different parts of the
      mitochondrial network are formed by different mechanisms. 

PMID- 26206317
TI  - Generics: are all immunosuppression agents created equally?
AB  - BACKGROUND: The Affordable Care Act initiated innumerable cost-containment
      measures, including promoting generic conversion from brand medications and
      directing the Food and Drug Administration to decrease requirements for generic
      approvals. Despite this mandate, few data existed on generic conversion of
      immunosuppressant medications with narrow therapeutic troughs. METHODS: A
      retrospective analysis of our initial experience with generic tacrolimus (n = 39)
      was performed using a control cohort from our renal transplant database. A
      rejection and cost analysis was performed using a consecutive 2-year prior cohort
      (n = 159) as a control to determine the effect of generic conversion on
      tacrolimus a narrow therapeutic index immunosuppressant medication. RESULTS:
      During the first year after transplantation, the generic group had a greater drug
      variability (20% +/- change in trough levels) that required more dosage
      adjustments (5.42 vs 3.59 drug dosage changes; P = .038) to obtain a stable dose,
      required increased number of intravenous magnesium infusions (4.95 vs 1.68
      infusions; P = .001), and incurred a greater incidence of rejection (23.1% vs
      10.2%; P = .024). A yearly institutional cost was evaluated against a negotiated
      $18,000/yearly central pharmacy cost savings compared with a $652,862
      institutional cost to treat unanticipated rejections. CONCLUSION: Programmatic
      conversion from brand to generic tacrolimus resulted in increased drug
      variability, a greater incidence of magnesium wasting, and more episodes of
      rejection, leading to increases in institutional costs of care. This government
      driven attempt at cost containment may be applicable to noncritical medications
      such as antibiotics and antihypertensives, but this policy should be reconsidered
      for narrow therapeutic index medications, such as tacrolimus and other
      immunosuppressant medications.

PMID- 26206316
TI  - High salt primes a specific activation state of macrophages, M(Na).
AB  - High salt is positively associated with the risk of many diseases. However,
      little is known about the mechanisms. Here we showed that high salt increased
      proinflammatory molecules, while decreased anti-inflammatory and proendocytic
      molecules in both human and mouse macrophages. High salt also potentiated
      lipopolysaccharide-induced macrophage activation and suppressed interleukin 4
      induced macrophage activation. High salt induced the proinflammatory aspects by
      activating p38/cFos and/or Erk1/2/cFos pathways, while inhibited the anti
      inflammatory and proendocytic aspects by Erk1/2/signal transducer and activator
      of transcription 6 pathway. Consistent with the in vitro results, high-salt diet
      increased proinflammatory gene expression of mouse alveolar macrophages. In mouse
      models of acute lung injury, high-salt diet aggravated lipopolysaccharide-induced
      pulmonary macrophage activation and inflammation in lungs. These results identify
      a novel macrophage activation state, M(Na), and high salt as a potential
      environmental risk factor for lung inflammation through the induction of M(Na). 

PMID- 26206318
TI  - Preoperative diagnosis with versus without MRI in resection for hepatocellular
      carcinoma.
AB  - PURPOSE: Although MRI has been considered one of the most sensitive diagnostic
      techniques for hepatocellular carcinoma (HCC), a clear-cut beneficial effect of
      the use of preoperative MRI remains unclear. We assessed whether preoperative MRI
      has a beneficial effect on outcomes in patients scheduled to undergo resection of
      HCC. METHODS: We evaluated 449 patients with 553 liver tumors. MRI was performed
      in 349 of these patients, but not in the other 100. Ultrasonography, dynamic CT,
      and angiography were performed in all patients. Diagnostic abilities and long
      term outcomes were compared between patients who did and did not undergo MRI.
      RESULTS: The MRI group (349 patients) had 419 liver tumors and the no MRI group
      (100 patients) had 134 tumors. Preoperatively, the size of the HCC did not differ
      between the MRI (median, 30 mm; range, 10-205) and the no MRI group (median, 34
      mm; range, 10-175; P = .99). The diagnostic accuracy was 98% in the MRI group and
      96% in the no MRI group. Recurrence-free survival rates at 5 years were 31% (95%
      CI, 20.9-42.5) in the no MRI group, compared with 26% (95% CI, 20.1-32.1) in the
      MRI (P = .45). Overall survival rates at 5 years were 57% (95% CI, 45.6-68.1) in
      the no MRI group and 60% (95% CI, 53.4-66.8) in the MRI group (P = .64). After
      analysis by propensity score matching in 100 pairs of patients, recurrence-free
      survival rates at 5 years were 31% (95% CI, 20.9-42.5) in the no MRI group,
      compared with 19% (95% CI, 10.3-30.9) in the MRI group (P = .54). Overall
      survival rates at 5 years were 57% (95% CI, 45.6-68.1) in the no MRI group and
      57% (95% CI, 43.2-68.8) in the MRI group (P = .92). CONCLUSION: MRI seemed to
      offer no beneficial impact on diagnostic abilities or long-term outcomes after
      resection for HCC and is thus of questionable value as a routine imaging modality
      when combined with CT and angiography clinical practice.

PMID- 26206320
TI  - Evidence for spending millions on deworming schoolchildren is inadequate, report
      says.

PMID- 26206321
TI  - Post-irradiation angiosarcoma of the breast: clinical presentation and outcome in
      a series of six cases.
AB  - Angiosarcoma of the breast represents 1% of all soft tissue breast tumors. With
      breast-conserving therapy (BCT) as standard in the last three decades, a new type
      of angiosarcoma has been reported: post-irradiation angiosarcoma (PIAS). A recent
      study based on the SEER database found an absolute risk for PIAS of seven per
      100,000 person-years for BCT patients. We present a retrospective analysis of the
      clinical characteristics, treatment, and outcome of six cases of PIAS treated in
      our institution from 1995 to 2010. Mean age at diagnosis of breast cancer was 68
      years (range 54-76 years). All patients underwent BCT. Adjuvant radiotherapy was
      given to all patients at doses of 45-50 Gy. Mean time from adjuvant radiotherapy
      to PIAS was 9.2 years (range 5.3-13.8 years); median follow-up from diagnosis of
      PIAS was 41.8 months (range 11-102 months). At diagnosis of PIAS, mean age of
      patients was 78 years (range 63-87 years). All patients underwent simple
      mastectomy, following which one patient received chemotherapy with doxorubicin
      and three patients received radiation therapy. Two patients developed local
      recurrence, one concurrent with metastatic disease. Another patient was diagnosed
      after 24 months with extensive small cell lung cancer and died of disease without
      recurrence of PIAS. Four patients are alive without evidence of recurrence. PIAS
      is a very rare sarcoma occurring after BCT. Careful observation after adjuvant
      radiotherapy is required. Standard treatment is the surgery with simple
      mastectomy and adjuvant radiotherapy; chemotherapy may be considered for more
      advanced cases.

PMID- 26206322
TI  - The challenge of detecting herds sub-clinically infected with Actinobacillus
      pleuropneumoniae.
AB  - The introduction into a naive herd of animals sub-clinically infected with
      Actinobacillus pleuropneumoniae (App) is frequently the cause of clinical
      pleuropneumonia and the identification of such infected herds is a priority in
      the control of disease. Different serological tests for App have been developed
      and a number of these are routinely used. Some are species-specific whereas
      others identify more specifically the serotype/serogroup involved which requires
      updated information about important serotypes recovered from diseased pigs in a
      given area/country. Serotyping methods based on molecular techniques have been
      developed lately and are ready to be used by most diagnostic laboratories. When
      non-conclusive serological results are obtained, direct detection of App from
      tonsils is sometimes attempted. This review addresses different techniques and
      approaches used to monitor herds sub-clinically infected by this important
      pathogen. 

PMID- 26206323
TI  - A novel NAD(P)H-dependent carbonyl reductase specifically expressed in the
      thyroidectomized chicken fatty liver: catalytic properties and crystal structure.
AB  - A gene encoding a functionally unknown protein that is specifically expressed in
      the thyroidectomized chicken fatty liver and has a predicted amino acid sequence
      similar to that of NAD(P)H-dependent carbonyl reductase was overexpressed in
      Escherichia coli; its product was purified and characterized. The expressed
      enzyme was an NAD(P)H-dependent broad substrate specificity carbonyl reductase
      and was inhibited by arachidonic acid at 1.5 MUm. Enzymological characterization
      indicated that the enzyme could be classified as a cytosolic-type carbonyl
      reductase. The enzyme's 3D structure was determined using the molecular
      replacement method at 1.98 A resolution in the presence of NADPH and ethylene
      glycol. The asymmetric unit consisted of two subunits, and a noncrystallographic
      twofold axis generated the functional dimer. The structures of the subunits, A
      and B, differed from each other. In subunit A, the active site contained an
      ethylene glycol molecule absent in subunit B. Consequently, Tyr172 in subunit A
      rotated by 103.7 degrees  in comparison with subunit B, which leads to active
      site closure in subunit A. In Y172A mutant, the Km value for 9,10
      phenanthrenequinone (model substrate) was 12.5 times higher than that for the
      wild-type enzyme, indicating that Tyr172 plays a key role in substrate binding in
      this carbonyl reductase. Because the Tyr172-containing active site lid structure
      (Ile164-Gln174) is not conserved in all known carbonyl reductases, our results
      provide new insights into substrate binding of carbonyl reductase. The catalytic
      properties and crystal structure revealed that thyroidectomized chicken fatty
      liver carbonyl reductase is a novel enzyme.

PMID- 26206324
TI  - Osteogenic Potential of Human Oral-Periosteal Cells (PCs) Isolated From Different
      Oral Origin: An In Vitro Study.
AB  - The periosteum is a specialized connective tissue containing multipotent stem
      cells capable of bone formation. In this study, we aimed at demonstrating that
      human oral periosteal cells derived from three different oral sites (upper
      vestibule, lower vestibule, and hard palate) represent an innovative cell source
      for maxillo-facial tissue engineering applications in terms of accessibility and
      self-commitment towards osteogenic lineage. Periosteal cells (PCs) were isolated
      from patients with different ages (20-30 yy, 40-50 yy, 50-60 yy); we then
      analyzed the in vitro proliferation capacity and the bone self-commitment of cell
      clones culturing them without any osteogenic supplement to support their
      differentiation. We found that oral PCs, independently of their origin and age of
      patients, are mesenchymal stem cells with stem cell characteristics (clonogenical
      and proliferative activity) and that, even in absence of any osteogenic
      induction, they undertake the osteoblast lineage after 45 days of culture. These
      results suggest that oral periosteal cells could replace mesenchymal cells from
      bone marrow in oral tissue-engineering applications.

PMID- 26206325
TI  - Sewage Sludge Polycyclic Aromatic Hydrocarbon (PAH) Decontamination Technique
      Based on the Utilization of a Lipopeptide Biosurfactant Extracted from Corn Steep
      Liquor.
AB  - A decontamination technique based on the utilization of a lipopeptide
      biosurfactant extracted from corn steep liquor has been developed to eliminate
      polycyclic aromatic hydrocarbons (PAHs) from sewage sludge. High concentrations
      of PAHs were used during experiments observing that 408.3 mg/kg of naphthalene
      was almost completely mobilized and biodegraded, only 1.7% of naphthalene
      remained in the sewage sludge, whereas anthracene and pyrene were reduced up to
      51.7 and 69.4%, respectively. The biodegradation of PAHs was fitted to several
      kinetic models (zero- and first-order kinetic models), observing good correlation
      coefficient values when biodegradation was described by the first-order kinetic
      model. Experimental results suggest that biosurfactant extracted from corn steep
      liquor may have great potential, as an ecofriendly washing agent, for the
      treatment of sewage sludge contaminated with PAHs. Therefore, in situ application
      of natural biosurfactants may be considered to be a good remediation alternative
      as they are not hazardous for water and soil organisms. 

PMID- 26206326
TI  - Burden of invasive mold disease in patients with acute myelogenous leukemia and
      in stem cell transplant recipients.

PMID- 26206327
TI  - Nursing and midwifery practice for maintenance of vascular access device patency.
      A cross-sectional survey.
AB  - BACKGROUND: Up to 85% of hospital in-patients will require some form of vascular
      access device to deliver essential fluids, drug therapy, nutrition and blood
      products, or facilitate sampling. The failure rate of these devices is
      unacceptably high, with 20-69% of peripheral intravenous catheters and 15-66% of
      central venous catheters failing due to occlusion, depending on the device,
      setting and population. A range of strategies have been developed to maintain
      device patency, including intermittent flushing. However, there is limited
      evidence informing flushing practice and little is known about the current
      flushing practices. OBJECTIVE: The aim of the study was to improve our
      understanding of current flushing practices for vascular access devices through a
      survey of practice. METHOD: A cross-sectional survey of nurses and midwives
      working in the State of Queensland, Australia was conducted using a 25-item
      electronic survey that was distributed via the local union membership database.
      RESULTS: A total of 1178 surveys were completed and analysed, with n=1068
      reporting peripheral device flushing and n=584 reporting central device flushing.
      The majority of respondents were registered nurses (55%) caring for adult
      patients (63%). A large proportion of respondents (72% for peripheral, 742/1028;
      80% for central, 451/566) were aware of their facility's policy for vascular
      access device flushing. Most nurses reported using sodium chloride 0.9% for
      flushing both peripheral (96%, 987/1028) and central devices (75%, 423/566). Some
      concentration of heparin saline was used by 25% of those flushing central
      devices. A 10-mL syringe was used by most respondents for flushing; however, 24%
      of respondents used smaller syringes in the peripheral device group. Use of
      prefilled syringes (either commercially prepared sterile or prefilled in the
      workplace) was limited to 10% and 11% respectively for each group. The frequency
      of flushing varied widely, with the most common response being pro re nata (23%
      peripheral and 21% central), or 6 hourly (23% peripheral and 22% central).
      Approximately half of respondents stated that there was no medical order or
      documentation for either peripheral or central device flushing. CONCLUSIONS:
      Flushing practices for vascular access device flushing appear to vary widely.
      Specific areas of practice that warrant further investigation include questions
      about the efficacy of heparin for central device flushing, increasing adherence
      to the recommended 10mL diameter syringe use, increased use of prefilled flush
      syringes, identifying and standardising optimal volumes and frequency of
      flushing, and improving documentation of flush orders and administration.

PMID- 26206328
TI  - Editorial: Stem Cell-Based and Gene Therapy for Hereditary Muscle Disorders.

PMID- 26206329
TI  - Blood metal ions after hybrid metal-on-polyethylene Exeter-Trident total hip
      replacement.
AB  - BACKGROUND: Metal-on-metal total hip replacements (THRs) with large femoral heads
      have been associated with elevated levels of cobalt (Co) and chromium (Cr), which
      have been attributed to high levels of wear at the articular surface. Our unit
      recently published data showing a significant increase in the mean levels of Co
      ions in patients with a 36-mm diameter femoral head with the metal-on
      polyethylene Trident-Accolade system. The aim of this study is to assess the
      levels of Co and Cr in the Exeter-Trident hybrid system, as similar findings
      would raise concern over the V40 taper trunnion. MATERIALS AND METHODS: The study
      included 83 patients (45 male and 38 female with a mean age of 75.6 years) who
      received Exeter-Trident hybrid metal-on-polyethylene THRs. The patients were then
      divided into two groups according to the diameter of the femoral head used-38
      patients in the 28-mm group (control), and 45 in the 36-mm (experimental) group.
      Serum levels of blood Co and Cr were analysed for all recruited patients.
      RESULTS: In the control group (28-mm femoral head) all Co and Cr values were
      normal (under the abnormal threshold), as were the experimental group (36-mm
      femoral head). The data values were below <10 nmol and <40 nmol for Co and Cr,
      respectively. CONCLUSION: Since the National Joint Registry (NJR) states that the
      Exeter femoral stem is the commonest cemented femoral stem prosthesis used in the
      UK, we found it imperative that these results are documented given the
      corresponding findings in the Trident-Accolade system in our previous study. This
      study provides relative reassurance that the issue does not lie with the V40
      taper trunnion, but raises suspicion that the issue may be with the titanium
      Accolade stem with large diameter femoral heads.

PMID- 26206330
TI  - Reversibility and two state behaviour in the thermal unfolding of oligomeric TIM
      barrel proteins.
AB  - Temperature is one of the main variables that modulate protein function and
      stability. Thermodynamic studies of oligomeric proteins, the dominant protein
      natural form, have been often hampered because irreversible aggregation and/or
      slow reactions are common. There are no reports on the reversible equilibrium
      thermal unfolding of proteins composed of (beta/alpha)8 barrel subunits, albeit
      this "TIM barrel" topology is one of the most abundant and versatile in nature.
      We studied the eponymous TIM barrel, triosephosphate isomerase (TIM), belonging
      to five species of different bacterial taxa. All of them were found to be
      catalytically efficient dimers. The three-dimensional structure of four enzymes
      was solved at high/medium resolution. Irreversibility and kinetic control were
      observed in the thermal unfolding of two TIMs, while for the other three the
      thermal unfolding was found to follow a two-state equilibrium reversible process.
      Shifts in the global stability curves of these three proteins are related to the
      organismal temperature range of optimal growth and modulated by variations in
      maximum stability temperature and in the enthalpy change at that temperature.
      Reversibility appears to correlate with the low isoelectric point, the absence of
      a residual structure in the unfolded state, small cavity volume in the native
      state, low conformational stability and a low melting temperature. Furthermore,
      the strong coupling between dimer dissociation and monomer unfolding may reduce
      aggregation and favour reversibility. It is therefore very thought-provoking to
      find that a common topological ensemble, such as the TIM barrel, can
      unfold/refold in the Anfinsen way, i.e. without the help of the cellular
      machinery. 

PMID- 26206331
TI  - Inhibition of Wild-Type p53-Expressing AML by the Novel Small Molecule HDM2
      Inhibitor CGM097.
AB  - The tumor suppressor p53 is a key regulator of apoptosis and functions upstream
      in the apoptotic cascade by both indirectly and directly regulating Bcl-2 family
      proteins. In cells expressing wild-type (WT) p53, the HDM2 protein binds to p53
      and blocks its activity. Inhibition of HDM2:p53 interaction activates p53 and
      causes apoptosis or cell-cycle arrest. Here, we investigated the ability of the
      novel HDM2 inhibitor CGM097 to potently and selectively kill WT p53-expressing
      AML cells. The antileukemic effects of CGM097 were studied using cell-based
      proliferation assays (human AML cell lines, primary AML patient cells, and normal
      bone marrow samples), apoptosis, and cell-cycle assays, ELISA, immunoblotting,
      and an AML patient-derived in vivo mouse model. CGM097 potently and selectively
      inhibited the proliferation of human AML cell lines and the majority of primary
      AML cells expressing WT p53, but not mutant p53, in a target-specific manner.
      Several patient samples that harbored mutant p53 were comparatively unresponsive
      to CGM097. Synergy was observed when CGM097 was combined with FLT3 inhibition
      against oncogenic FLT3-expressing cells cultured both in the absence as well as
      the presence of cytoprotective stromal-secreted cytokines, as well as when
      combined with MEK inhibition in cells with activated MAPK signaling. Finally,
      CGM097 was effective in reducing leukemia burden in vivo. These data suggest that
      CGM097 is a promising treatment for AML characterized as harboring WT p53 as a
      single agent, as well as in combination with other therapies targeting oncogene
      activated pathways that drive AML.

PMID- 26206332
TI  - Silencing Egr1 Attenuates Radiation-Induced Apoptosis in Normal Tissues while
      Killing Cancer Cells and Delaying Tumor Growth.
AB  - Normal tissue toxicity reduces the therapeutic index of radiotherapy and
      decreases the quality of life for cancer survivors. Apoptosis is a key element of
      the radiation response in normal tissues like the hippocampus and small
      intestine, resulting in neurocognitive disorders and intestinal malabsorption.
      The Early Growth Response 1 (Egr1) transcription factor mediates radiation
      induced apoptosis by activating the transcription of proapoptosis genes in
      response to ionizing radiation (IR). Therefore, we hypothesized that the genetic
      abrogation of Egr1 and the pharmacologic inhibition of its transcriptional
      activity could attenuate radiation-induced apoptosis in normal tissues. We
      demonstrated that Egr1-null mice had less apoptosis in the hippocampus and
      intestine following irradiation as compared with their wild-type littermates. A
      similar result was achieved using Mithramycin A (MMA) to prevent binding of Egr1
      to target promoters in the mouse intestine. Abolishing Egr1 expression using
      shRNA dampened apoptosis and enhanced the clonogenic survival of irradiated HT22
      hippocampal neuronal cells and IEC6 intestinal epithelial cells. Mechanistically,
      these events involved an abrogation of p53 induction by IR and an increase in the
      ratio of Bcl-2/Bax expression. In contrast, targeted silencing of Egr1 in two
      cancer cell lines (GL261 glioma cells and HCT116 colorectal cancer cells) was not
      radioprotective, since it reduced their growth while also sensitizing them to
      radiation-induced death. Further, Egr1 depletion delayed the growth of
      heterotopically implanted GL261 and HCT116 tumors. These results support the
      potential of silencing Egr1 in order to minimize the normal tissue complications
      associated with radiotherapy while enhancing tumor control.

PMID- 26206333
TI  - NSCLC Driven by DDR2 Mutation Is Sensitive to Dasatinib and JQ1 Combination
      Therapy.
AB  - Genetically engineered mouse models of lung cancer have demonstrated an important
      role in understanding the function of novel lung cancer oncogenes and tumor
      suppressor genes identified in genomic studies of human lung cancer. Furthermore,
      these models are important platforms for preclinical therapeutic studies. Here,
      we generated a mouse model of lung adenocarcinoma driven by mutation of the
      discoidin domain receptor 2 (DDR2) gene combined with loss of TP53.
      DDR2(L63V);TP53(L/L) mice developed poorly differentiated lung adenocarcinomas in
      all transgenic animals analyzed with a latency of 40 to 50 weeks and a median
      survival of 67.5 weeks. Mice expressing wild-type DDR2 with combined TP53 loss
      did not form lung cancers. DDR2(L63V);TP53(L/L) tumors displayed robust
      expression of DDR2 and immunohistochemical markers of lung adenocarcinoma
      comparable with previously generated models, though also displayed concomitant
      expression of the squamous cell markers p63 and SOX2. Tumor-derived cell lines
      were not solely DDR2 dependent and displayed upregulation of and partial
      dependence on MYCN. Combined treatment with the multitargeted DDR2 inhibitor
      dasatinib and BET inhibitor JQ1 inhibited tumor growth in vitro and in vivo.
      Together, these results suggest that DDR2 mutation can drive lung cancer
      initiation in vivo and provide a novel mouse model for lung cancer therapeutics
      studies.

PMID- 26206334
TI  - R-Ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors
      Critical for Invasion and Metastasis.
AB  - Cdc42 (cell division control protein 42) and Rac1 (Ras-related C3 botulinum toxin
      substrate 1) are attractive therapeutic targets in ovarian cancer based on
      established importance in tumor cell migration, adhesion, and invasion. Despite a
      predicted benefit, targeting GTPases has not yet been translated to clinical
      practice. We previously established that Cdc42 and constitutively active Rac1b
      are overexpressed in primary ovarian tumor tissues. Through high-throughput
      screening and computational shape homology approaches, we identified R-ketorolac
      as a Cdc42 and Rac1 inhibitor, distinct from the anti-inflammatory,
      cyclooxygenase inhibitory activity of S-ketorolac. In the present study, we
      establish R-ketorolac as an allosteric inhibitor of Cdc42 and Rac1. Cell-based
      assays validate R-ketorolac activity against Cdc42 and Rac1. Studies on
      immortalized human ovarian adenocarcinoma cells (SKOV3ip) and primary patient
      derived ovarian cancer cells show that R-ketorolac is a robust inhibitor of
      growth factor or serum-dependent Cdc42 and Rac1 activation with a potency and
      cellular efficacy similar to small-molecule inhibitors of Cdc42
      (CID2950007/ML141) and Rac1 (NSC23766). Furthermore, GTPase inhibition by R
      ketorolac reduces downstream p21-activated kinases (PAK1/PAK2) effector
      activation by >80%. Multiple assays of cell behavior using SKOV3ip and primary
      patient-derived ovarian cancer cells show that R-ketorolac significantly inhibits
      cell adhesion, migration, and invasion. In summary, we provide evidence for R
      ketorolac as a direct inhibitor of Cdc42 and Rac1 that is capable of modulating
      downstream GTPase-dependent, physiologic responses, which are critical to tumor
      metastasis. Our findings demonstrate the selective inhibition of Cdc42 and Rac1
      GTPases by an FDA-approved drug, racemic ketorolac, that can be used in humans.

PMID- 26206335
TI  - Polymorphisms in Genes Involved in EGFR Turnover Are Predictive for Cetuximab
      Efficacy in Colorectal Cancer.
AB  - Transmembrane receptors, such as the EGFR, are regulated by their turnover, which
      is dependent on the ubiquitin-proteasome system. We tested in two independent
      study cohorts whether SNPs in genes involved in EGFR turnover predict clinical
      outcome in cetuximab-treated metastatic colorectal cancer (mCRC) patients. The
      following SNPs involved in EGFR degradation were analyzed in a screening cohort
      of 108 patients treated with cetuximab in the chemorefractory setting: c-CBL
      (rs7105971; rs4938637; rs4938638; rs251837), EPS15 (rs17567; rs7308; rs1065754),
      NAE1 (rs363169; rs363170; rs363172), SH3KBP1 (rs7051590; rs5955820; rs1017874;
      rs11795873), SGIP1 (rs604737; rs6570808; rs7526812), UBE2M (rs895364; rs895374),
      and UBE2L3 (rs5754216). SNPs showing an association with response or survival
      were analyzed in BRAF and RAS wild-type samples from the FIRE-3 study. One
      hundred and fifty-three FOLFIRI plus cetuximab-treated patients served as
      validation set, and 168 patients of the FOLFIRI plus bevacizumab arm served as
      controls. EGFR FISH was done in 138 samples to test whether significant SNPs were
      associated with EGFR expression. UBE2M rs895374 was significantly associated with
      progression-free survival (log-rank P = 0.005; HR, 0.60) within cetuximab-treated
      patients. No association with bevacizumab-treated patients (n = 168) could be
      established (P = 0.56; HR, 0.90). rs895374 genotype did not affect EGFR FISH
      measurements. EGFR recycling is an interesting mechanism of secondary resistance
      to cetuximab in mCRC. This is the first report suggesting that germline
      polymorphisms in the degradation process predict efficacy of cetuximab in
      patients with mCRC. Genes involved in EGFR turnover may be new targets in the
      treatment of mCRC.

PMID- 26206336
TI  - Intrapulmonary Delivery of CpG Microparticles Eliminates Lung Tumors.
AB  - CpG oligonucleotides (ODN) stimulate the innate immune system by triggering cells
      that express TLR9. The resulting response promotes tumor regression, an effect
      optimized by delivery of CpG ODN to the tumor site. This work examines the effect
      of instilling CpG ODN adsorbed onto polyketal microparticles (CpG-MP) into the
      lungs of mice with non-small cell lung cancer. Intrapulmonary delivery of CpG-MP
      improved ODN uptake and retention at the tumor site, thereby inducing a stronger
      Th1 response than systemically administered or unadsorbed CpG ODN. CpG-MP
      reversed the immunosuppression that characterized the tumor microenvironment by
      (i) decreasing the number of immunosuppressive Tregs and M2 macrophages while
      (ii) increasing the number of tumoricidal CD8(+) T cells and M1 macrophages.
      These effects promoted tumor regression and culminated in 82% permanent survival
      of mice with otherwise fatal Lewis lung cancer.

PMID- 26206337
TI  - Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked
      Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations.
AB  - We assessed the antileukemic activity of 2-deoxy-d-glucose (2-DG) through the
      modulation of expression of receptor tyrosine kinases (RTK) commonly mutated in
      acute myeloid leukemia (AML). We used human leukemic cell lines cells, both in
      vitro and in vivo, as well as leukemic samples from AML patients to demonstrate
      the role of 2-DG in tumor cell growth inhibition. 2-DG, through N-linked
      glycosylation inhibition, affected the cell-surface expression and cellular
      signaling of both FTL3-ITD and mutated c-KIT and induced apoptotic cell death.
      Leukemic cells harboring these mutated RTKs (MV4-11, MOLM-14, Kasumi-1, and TF-1
      c-KIT D816V) were the most sensitive to 2-DG treatment in vitro as compared with
      nonmutated cells. 2-DG activity was also demonstrated in leukemic cells harboring
      FLT3-TKD mutations resistant to the tyrosine kinase inhibitor (TKI) quizartinib.
      Moreover, the antileukemic activity of 2-DG was particularly marked in c-KIT
      mutated cell lines and cell samples from core binding factor-AML patients. In
      these cells, 2-DG inhibited the cell-surface expression of c-KIT, abrogated STAT3
      and MAPK-ERK pathways, and strongly downregulated the expression of the receptor
      resulting in a strong in vivo effect in NOD/SCID mice xenografted with Kasumi-1
      cells. Finally, we showed that 2-DG decreases Mcl-1 protein expression in AML
      cells and induces sensitization to both the BH3 mimetic inhibitor of Bcl-xL, Bcl
      2 and Bcl-w, ABT-737, and cytarabine. In conclusion, 2-DG displays a significant
      antileukemic activity in AML with FLT3-ITD or KIT mutations, opening a new
      therapeutic window in a subset of AML with mutated RTKs.

PMID- 26206338
TI  - Assessment of the In Vivo Activity of PI3K and MEK Inhibitors in Genetically
      Defined Models of Colorectal Cancer.
AB  - The objective of tailoring medicines for cancer patients according to the
      molecular profile of their disease holds great promise for the improvement of
      cancer therapy. Nevertheless, this approach has been limited, in part, due to the
      lack of predictive and informative preclinical studies. Herein, we describe an
      assessment of the therapeutic potential of targeting PI3K/mTOR and MAPK signaling
      in genetically defined mouse models of colorectal cancer mirroring disease
      subtypes targeted for novel therapy in the FOCUS4 trial. Our studies demonstrate
      that dual PI3K/mTOR inhibition is highly effective in invasive adenocarcinoma
      models characterized by combinatorial mutations in Apc and Pten; Apc and Kras;
      and Apc, Pten and Kras. MEK inhibition was effective in the combinatorial Apc and
      Kras setting, but had no impact in either Apc Pten mutants or in Apc Pten Kras
      triple mutants. Furthermore, we describe the importance of scheduling for
      combination studies and show that although no additional benefit is gained in Apc
      Pten mice, combination of PI3K/mTOR and MAPK inhibition leads to an additive
      benefit in survival in Apc Kras mice and a synergistic increase in survival in
      Apc Pten Kras mice. This is the first study using robust colorectal cancer
      genetically engineered mouse models to support the validity of PI3K/mTOR and MEK
      inhibitors as tailored therapies for colorectal cancer and highlight the
      potential importance of drug scheduling in the clinic.

PMID- 26206339
TI  - eNOS uncoupling in the cerebellum after BBB disruption by exposure to Phoneutria
      nigriventer spider venom.
AB  - Numerous studies have shown that the venom of Phoneutria nigriventer (PNV) armed
      spider causes excitotoxic signals and blood-brain barrier breakdown (BBBb) in
      rats. Nitric oxide (NO) is a signaling molecule which has a role in endothelium
      homeostasis and vascular health. The present study investigated the relevance of
      endothelial NO synthase (eNOS) uncoupling to clinical neurotoxic evolution
      induced by PNV. eNOS immunoblotting of cerebellum lysates processed through low
      temperature SDS-PAGE revealed significant increased monomerization of the enzyme
      at critical periods of severe envenoming (1-2 h), whereas eNOS dimerization
      reversal paralleled to amelioration of animals condition (5-72 h). Moreover, eNOS
      uncoupling was accompanied by increased expression in calcium-sensing calmodulin
      protein and calcium-binding calbindin-D28 protein in cerebellar neurons. It is
      known that greater eNOS monomers than dimers implies the inability of eNOS to
      produce NO leading to superoxide production and endothelial/vascular barrier
      dysfunction. We suggest that transient eNOS deactivation and disturbances in
      calcium handling reduce NO production and enhance production of free radicals
      thus contributing to endothelial dysfunction in the cerebellum of envenomed rats.
      In addition, eNOS uncoupling compromises the enzyme capacity to respond to shear
      stress contributing to perivascular edema and it is one of the mechanisms
      involved in the BBBb promoted by PNV.

PMID- 26206340
TI  - Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid
      and a selective noradrenaline re-uptake inhibitor in nerve injury-induced
      neuropathic mice.
AB  - BACKGROUND: Combining drugs not only reduces specific adverse effects of each of
      the drug at a higher dose but also may lead to enhanced efficacy. Tapentadol is a
      recently discovered analgesic possessing MU-opioid receptor agonism and
      noradrenaline re-uptake inhibition in a single molecule. Taking into
      consideration, the pharmacological similarities between opioids and cannabinoids,
      we assumed that combination of cannabinoids with noradrenaline re-uptake
      inhibitors might also be effective. We therefore aimed to determine whether
      combining 1:1, 1:3 and 3:1 fixed ratios of the synthetic cannabinoid WIN 55,212-2
      and the selective noradrenaline re-uptake inhibitor maprotiline exert anti
      allodynic synergy on nerve-injured neuropathic mice. METHODS: Partial tight
      ligation of the sciatic nerve was made in mice; on pre-operative and post
      operative 15 days basal mechanical allodynia, cold allodynia and motor function
      were assessed using von Frey filaments, hot/cold plate and rota rod apparatus.
      RESULTS: Mechanical and cold allodynia developed in all groups on post-operative
      15 days. Development of cold allodynia was statistically significant in all
      groups (p < 0.05); therefore, cold allodynia was used in combination studies. As
      shown by isobolographic analysis, interactions of 1:1 and 3:1 ratios of WIN
      55,212-2:maprotiline combinations were supra-additive, whereas 1:3 ratio was sub
      additive. CONCLUSIONS: Overall, our data suggest that combination of a
      cannabinoid with a selective noradrenaline re-uptake inhibitor may offer a
      beneficial treatment option for neuropathic pain.

PMID- 26206341
TI  - Risk of new-onset heart failure in patients using sitagliptin: a population-based
      cohort study.
AB  - AIMS: To examine whether patients using sitagliptin at the time of an acute
      coronary syndrome event are at increased risk of incident heart failure compared
      with those not exposed. METHODS: Using US claims data, people with diabetes
      without a history of heart failure in the 3 years before hospitalization for
      acute coronary syndrome were identified for the period 2004 to 2010. We used a
      nested case-control design, whereby cases were patients who developed incident
      heart failure <30 days after admission to hospital for acute coronary syndrome
      and were matched by age and sex with up to 10 controls with no heart failure.
      Subjects exposed or not exposed to sitagliptin in the 90 days before acute
      coronary syndrome admission were compared using conditional logistic regression
      after adjustment for clinical and laboratory data, healthcare utilization and
      propensity scores. RESULTS: In total, 457 cases of heart failure developing de
      novo after diagnosis of acute coronary syndrome were matched to 4570 controls.
      The average age of the subjects was 55 years and 65% were male. Overall, 11 of
      147 (7%) people exposed to sitagliptin developed heart failure compared with 446
      of the 4880 people not exposed (9%, adjusted odds ratio 0.75, 95% CI 0.38-1.46;
      P=0.40). Sitagliptin exposure before acute coronary syndrome was not associated
      with an increased risk of death or heart failure combined (7% vs 9%, adjusted
      odds ratio 0.66, 95% CI 0.34-1.28). CONCLUSIONS: In our sample of patients who
      are at high risk of heart failure after acute coronary syndrome, sitagliptin
      exposure was not associated with an increased risk of de novo heart failure.

PMID- 26206342
TI  - Satisfaction With Life, Coping, and Spirituality Among Urban Families.
AB  - BACKGROUND: Urban families face many challenges that affect life satisfaction,
      including low income, limited access to resources, and unstable neighborhoods.
      PURPOSE: To investigate life satisfaction and identify potential mediators:
      neighborhood stability, emotional coping strategies, religion, and spirituality.
      METHODS: A convenience sample of families presenting to an urban primary care
      clinic for routine care filled out an anonymous, voluntary survey that included
      demographic data, the Satisfaction with Life Scale (SWLS), the Spiritual
      Inventory and Beliefs Scale, and an emotional coping inventory. RESULTS: 127
      individuals filled out the survey. Life satisfaction was high (21.3 +/- 9).
      Families in the lowest quartile of the SWLS were 4.5 times as likely to have a
      child with a chronic medical illness. SWLS correlated with strategy planning (r =
      0.24, P < .01), external practices of religion (r = 0.23, P < .01), and humility
      (r = 0.18, P < .05). CONCLUSIONS: Encouraging patients' involvement in religion
      and certain coping strategies, especially among those families coping with
      children with special health care needs, may improve life satisfaction.

PMID- 26206343
TI  - Circulating miR-200-family micro-RNAs have altered plasma levels in patients with
      endometriosis and vary with blood collection time.
AB  - OBJECTIVE: To determine whether circulating micro-RNA (miR) 200a, miR-200b, and
      miR-141 have altered levels in patients with endometriosis compared with control
      individuals. DESIGN: Experimental laboratory study. SETTING: University.
      PATIENT(S): Patients with endometriosis (n = 61), laparoscopically confirmed
      endometriosis-free women (n = 35), and self-reported healthy women (n = 30) were
      included in the study. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Plasma
      miRNA levels in endometriosis patients and control subjects. RESULT(S): We found
      that the levels of studied miRNAs varied with blood collection time, being lower
      in the morning than in the evening. When blood collection time was taken into
      account, the results revealed significantly lower levels of miR-200a and miR-141
      in the evening plasma samples of women with endometriosis compared with
      surgically confirmed disease-free patients. However, the evening-sample levels of
      all three miRNAs were significantly lower in patients with stage I-II
      endometriosis than in endometriosis-free control subjects. In cases of stage III
      IV endometriosis, only miR-200a levels were significantly lower compared with
      patients without endometriosis. Circulating miR-200a showed the best
      discriminative power to differentiate women with endometriosis from patients with
      similar complaints but without the disease. CONCLUSION(S): Our findings suggest
      that miR-200a and miR-141 have a potential as novel noninvasive biomarkers for
      endometriosis. In addition, we found that the plasma miR-200a, miR-200b and miR
      141 levels vary with blood sampling time, so it is important to take the sample
      collection time into account when studying miRNAs as biomarkers.

PMID- 26206344
TI  - Men's meat intake and treatment outcomes among couples undergoing assisted
      reproduction.
AB  - OBJECTIVE: To study the relationship between men's meat intake and clinical
      outcomes in couples undergoing infertility treatment with the use of assisted
      reproductive technology (ART). DESIGN: Prospective cohort study. SETTING:
      Fertility center. PATIENT(S): A total of 141 men whose female partners underwent
      246 ART cycles from 2007 to 2014. INTERVENTION(S): None. Total and specific types
      of meat intake were estimated from dietary questionnaires. MAIN OUTCOME
      MEASURE(S): Fertilization, implantation, clinical pregnancy, and live-birth rates
      per initiated cycle. Mixed-effects models account for multiple IVF cycles per
      woman. RESULT(S): There was a positive association between poultry intake and
      fertilization rate, with a 13% higher fertilization rate among men in the highest
      quartile of poultry intake compared with those in the lowest quartile (78% vs.
      65%). Processed meat intake was inversely related to fertilization rate in
      conventional IVF cycles but not in IVF cycles using intracytoplasmic sperm
      injection. The adjusted fertilization rates for men in increasing quartiles of
      processed meat intake were 82%, 67%, 70%, and 54% in conventional IVF cycles.
      Men's total meat intake, including intake of specific types of meat, was not
      associated with implantation, clinical pregnancy, or live-birth rates.
      CONCLUSION(S): Poultry intake was positively associated with fertilization rates,
      whereas processed meat intake was negatively associated with fertilization rates
      among couples undergoing conventional IVF. This, however, did not translate into
      associations with clinical pregnancy or live-birth rates.

PMID- 26206345
TI  - In Silico Identification for alpha-Amino-epsilon-Caprolactam Racemases by Using
      Information on the Structure and Function Relationship.
AB  - In silico identification for enzymes having desired functions is attractive
      because there is a possibility that numerous desirable enzymes have been
      deposited in databases. In this study, alpha-amino-epsilon-caprolactam (ACL)
      racemases were searched from the NCBI protein database. Four hundred thirteen
      fold-type I pyridoxal 5'-phosphate-dependent enzymes which are considered to
      contain sequences of ACL racemase were firstly obtained by submitting the
      sequence of ACL racemase from Achromobacter obae to the database. By identifying
      Lys241 as a key amino acid residue, 13 candidates for ACL racemase were selected.
      Then, putative ACL racemase genes were synthesized as codon-optimized sequences
      for expression in Escherichia coli. They were subcloned and expressed in E. coli
      BL21 and underwent His-tag purification. ACL and amino acid amide racemizing
      activities were detected among ten of the candidates. The locus tags Oant_4493,
      Smed_5339, and CSE45_2055 derived from Ochrobactrum anthropi ATCC49188,
      Sinorhizobium medicae WSM 419, and Citreicella sp. SE45, respectively, showed
      higher racemization activity against D- and L-ACLs rather than that of ACL
      racemase from A. obae. Our results demonstrate that the newly discovered ACL
      racemases were unique from ACL racemase from A. obae and might be useful for
      applications in dynamic kinetic resolution for D- or L-amino acid production.

PMID- 26206346
TI  - Ultrasonography of major salivary glands: a highly specific tool for
      distinguishing primary Sjogren's syndrome from undifferentiated connective tissue
      diseases.
AB  - OBJECTIVES: Recently, convincing data have been published on the value of
      salivary gland ultrasonography (SGUS) in differentiating primary SS from non
      immune-mediated sicca syndrome. Limited data are available regarding the
      diagnostic accuracy of SGUS in distinguishing SS from other rheumatic diseases.
      The purpose of this study was to assess the usefulness of SGUS in distinguishing
      patients with SS from those with xerostomia and/or xerophthalmia and a diagnosis
      of stable UCTD. METHODS: This cross-sectional study consecutively enrolled 150
      patients either diagnosed with SS (as established by the American-European
      Consensus Group criteria) or affected by UCTD but not SS. Parotid and
      submandibular glands on both sides were assessed for size, parenchymal
      echogenicity and inhomogeneity by means of SGUS, which was performed by a
      radiologist blinded to the diagnosis. Echostructural alterations of the salivary
      glands were graded from 0 to 3 (cut-off >2). RESULTS: This study included 109
      patients: 55 with SS and 54 with UCTD. Patients with SS showed a higher SGUS
      score in comparison with those with UCTD [mean 2.2 (s.d. 1.8) vs 0.2 (s.d. 0.5),
      P < 0.0001]. The SGUS cut-off >2 showed a sensitivity of 65%, a specificity of
      96%, a positive predictive value of 95% and a negative predictive value of 73%
      for SS diagnosis. A significant correlation was also found between the SGUS score
      and the minor salivary gland biopsy/focus score (r = 0.484, P < 0.0001).
      CONCLUSION: This study confirmed the good sensitivity and the high specificity of
      SGUS in differentiating SS from other CTDs.

PMID- 26206347
TI  - Genome-wide copy number changes and CD133 expression characterized distinct
      subset of colon polyps: differentiation between incidental polyps and cancer
      associated polyps.
AB  - PURPOSE: Colorectal polyps are generally believed to be the precursors of
      colorectal cancers (CRC); however, the proportion and speed of progression
      differed widely in different subsets of polyps. Using microarray-based
      comparative genomic hybridization (aCGH) platform and CD133 immunostaining, we
      characterized colon polyps according to their association with CRC that developed
      in the same individual. PATIENTS AND METHODS: aCGH was performed to unveil
      genomic changes in 18 cancer-synchronous polyps (CSP), and 9 cancer-preceding
      polyps (CPP), together with their corresponding cancers and 16 cases of
      incidental polyps (IP), were examined for comparison. aCGH profiles were analyzed
      to determine the clonal relationship (CR) between the paired adenoma and
      carcinoma. CD133 expressions in each subset of polyps were quantified by
      immunohistochemistry (IHC) staining. RESULTS: Progressive genomic changes were
      observed from IP, CSP/CPP to CRC; they encompass an entire chromosomal region in
      IP and sub-chromosomal region in CSP/CPP and CRC. CR analyses demonstrated that
      50 % of CSP and 67 % of CPP were clonally related to the concurrent or later
      developed carcinomas, respectively. The CD133 expression levels were
      significantly higher in CSP/CPP than those in IP (P < 0.0001) and even higher in
      CSP/CPP that were clonally related to their corresponding carcinomas than CSP/CPP
      that were unrelated (P < 0.05). CONCLUSIONS: There were more genomic changes in
      CSP/CPP than IP; more than half of the CSP/CPP were clonally related to the
      corresponding carcinomas. Genomic changes at sub-chromosomal regions and/or high
      CD133 expression were associated with CSP/CPP and highlighted their carcinogenic
      potential.

PMID- 26206348
TI  - Comparison of the pathological response of the mesorectal positive nodes between
      short-course chemoradiotherapy with delayed surgery and long-course
      chemoradiotherapy in patients with rectal cancer.
AB  - BACKGROUND: The aim of this study was to compare the pathological response of
      mesorectal positive nodes between short-course chemoradiotherapy with delayed
      surgery (SCRT-delay) and long-course chemoradiotherapy (LC-CRT) in patients with
      rectal cancer. METHOD: The resected primary tumor specimens following the two
      different approaches were assessed utilizing the tumor regression grade (TRG 0
      4), and each positive lymph node was assessed according to the lymph node
      regression grade (LRG 1-3), with TRG 4 and LRG 3 indicating total regression. The
      lymph node sizes were measured to elucidate any correlation with LRG scores.
      RESULTS: Seventy-four patients with ypN-positive rectal cancer had 220 positive
      lymph nodes following the SCRT-delay, and 48 patients had 141 positive lymph
      nodes following the LC-CRT. The distribution of LRG 1/2/3 in the two groups was
      123/72/25 and 60/31/50 (p < 0.001), respectively, and the distribution of TRG
      0/1/2/3/4 in the two groups was 36/19/19/0 and 12/15/20/1 (p = 0.005),
      respectively. The requirements of total regression of positive lymph nodes were a
      primary tumor degenerated to TRG 3 with a size less than 6 mm in SCRT-delay
      (sensitivity, 60.9 %) or a primary tumor degenerated to TRG 2-4 with a size less
      than 5 mm at TRG 2 (sensitivity, 57.6 %) or 6 mm at TRG 3 and 4 (sensitivity,
      84.2 %) in LC-CRT as indicated by the receiver operating characteristic curve
      analysis. CONCLUSION: The tumor regression effect of LC-CRT on the primary tumor
      and positive nodes was more favorable than SCRT-delay, and LC-CRT is able to
      predict the LRG 3 response with a high sensitivity.

PMID- 26206349
TI  - Comparison of Genomic Selection Models to Predict Flowering Time and Spike Grain
      Number in Two Hexaploid Wheat Doubled Haploid Populations.
AB  - Genomic selection (GS) is becoming an important selection tool in crop breeding.
      In this study, we compared the ability of different GS models to predict time to
      young microspore (TYM), a flowering time-related trait, spike grain number under
      control conditions (SGNC) and spike grain number under osmotic stress conditions
      (SGNO) in two wheat biparental doubled haploid populations with unrelated
      parents. Prediction accuracies were compared using BayesB, Bayesian least
      absolute shrinkage and selection operator (Bayesian LASSO / BL), ridge regression
      best linear unbiased prediction (RR-BLUP), partial least square regression (PLS),
      and sparse partial least square regression (SPLS) models. Prediction accuracy was
      tested with 10-fold cross-validation within a population and with independent
      validation in which marker effects from one population were used to predict
      traits in the other population. High prediction accuracies were obtained for TYM
      (0.51-0.84), whereas moderate to low accuracies were observed for SGNC (0.10
      0.42) and SGNO (0.27-0.46) using cross-validation. Prediction accuracies based on
      independent validation are generally lower than those based on cross-validation.
      BayesB and SPLS outperformed all other models in predicting TYM with both cross
      validation and independent validation. Although the accuracies of all models are
      similar in predicting SGNC and SGNO with cross-validation, BayesB and SPLS had
      the highest accuracy in predicting SGNC with independent validation. In
      independent validation, accuracies of all the models increased by using only the
      QTL-linked markers. Results from this study indicate that BayesB and SPLS capture
      the linkage disequilibrium between markers and traits effectively leading to
      higher accuracies. Excluding markers from QTL studies reduces prediction
      accuracies. 

PMID- 26206350
TI  - Development of a Tightly Controlled Off Switch for Saccharomyces cerevisiae
      Regulated by Camphor, a Low-Cost Natural Product.
AB  - Here we describe the engineering of a distant homolog of the Tet repressor, CamR,
      isolated from Pseudomonas putida, that is regulated by camphor, a very
      inexpensive small molecule (at micromolar concentrations) for use in
      Saccharomyces cerevisiae. The repressor was engineered by expression from a
      constitutive yeast promoter, fusion to a viral activator protein cassette, and
      codon optimization. A suitable promoter responsive to the CamR fusion protein was
      engineered by embedding a P. putida operator binding sequence within an upstream
      activating sequence (UAS)-less CYC1 promoter from S. cerevisiae. The switch,
      named the Camphor-Off switch, activates expression of a reporter gene in camphor
      free media and represses it with micromolar concentrations of camphor. 

PMID- 26206351
TI  - Developmental changes in hypoxic exposure and responses to anoxia in Drosophila
      melanogaster.
AB  - Holometabolous insects undergo dramatic morphological and physiological changes
      during ontogeny. In particular, the larvae of many holometabolous insects are
      specialized to feed in soil, water or dung, inside plant structures, or inside
      other organisms as parasites where they may commonly experience hypoxia or
      anoxia. In contrast, holometabolous adults usually are winged and live with
      access to air. Here, we show that larval Drosophila melanogaster experience
      severe hypoxia in their normal laboratory environments; third instar larvae feed
      by tunneling into a medium without usable oxygen. Larvae move strongly in anoxia
      for many minutes, while adults (like most other adult insects) are quickly
      paralyzed. Adults survive anoxia nearly an order of magnitude longer than larvae
      (LT50: 8.3 versus 1 h). Plausibly, the paralysis of adults is a programmed
      response to reduce ATP need and enhance survival. In support of that hypothesis,
      larvae produce lactate at 3* greater rates than adults in anoxia. However, when
      immobile in anoxia, larvae and adults are similarly able to decrease their
      metabolic rate, to about 3% of normoxic conditions. These data suggest that
      Drosophila larvae and adults have been differentially selected for behavioral and
      metabolic responses to anoxia, with larvae exhibiting vigorous escape behavior
      likely enabling release from viscous anoxic media to predictably normoxic air,
      while the paralysis behavior of adults maximizes their chances of surviving
      flooding events of unpredictable duration. Developmental remodeling of behavioral
      and metabolic strategies to hypoxia/anoxia is a previously unrecognized major
      attribute of holometabolism.

PMID- 26206353
TI  - Effect of shear forces and ageing on the compliance of adhesive pads in adult
      cockroaches.
AB  - The flexibility of insect adhesive pads is crucial for their ability to attach on
      rough surfaces. Here, we used transparent substrates with micropillars to test in
      adult cockroaches (Nauphoeta cinerea) whether and how the stiffness of smooth
      adhesive pads changes when shear forces are applied, and whether the insect's age
      has any influence. We found that during pulls towards the body, the pad's ability
      to conform to the surface microstructures was improved in comparison to a contact
      without shear, suggesting that shear forces make the pad more compliant. The
      mechanism underlying this shear-dependent increase in compliance is still
      unclear. The effect was not explained by viscoelastic creep, changes in normal
      pressure, or shear-induced pad rolling, which brings new areas of cuticle into
      surface contact. Adhesive pads were significantly stiffer in older cockroaches.
      Stiffness increased most rapidly in cockroaches aged between 2.5 and 4 months.
      This increase is probably based on wear and repair of the delicate adhesive
      cuticle. Recent wear (visualised by Methylene Blue staining) was not age
      dependent, whereas permanent damage (visible as brown scars) accumulated with
      age, reducing the pads' flexibility.

PMID- 26206352
TI  - Light sensitivity in a vertebrate mechanoreceptor?
AB  - Using immunohistochemistry and western blot analysis, we demonstrate that
      melanopsin is localised in cells around the central pore of lateral line
      neuromasts in the African clawed frog, Xenopus laevis. Since melanopsin is a
      known photoreceptor pigment with diverse functions in vertebrates, we suggest
      that the lateral line of Xenopus laevis, which is primarily a mechanoreceptor,
      might also be light sensitive. Potential functions of such photosensitivity are
      discussed, including its role in mediating locomotor responses following dermal
      illumination. 

PMID- 26206354
TI  - Skinned fibres produce the same power and force as intact fibre bundles from
      muscle of wild rabbits.
AB  - Skinned fibres have advantages for comparing the muscle properties of different
      animal species because they can be prepared from a needle biopsy taken under
      field conditions. However, it is not clear how well the contractile properties of
      skinned fibres reflect the properties of the muscle fibres in vivo. Here, we
      compare the mechanical performance of intact fibre bundles and skinned fibres
      from muscle of the same animals. This is the first such direct comparison.
      Maximum power and isometric force were measured at 25  degrees C using peroneus
      longus (PL) and extensor digiti-V (ED-V) muscles from wild rabbits (Oryctolagus
      cuniculus). More than 90% of the fibres in these muscles are fast-twitch, type 2
      fibres. Maximum power was measured in force-clamp experiments. We show that
      maximum power per volume was the same in intact (121.3 +/- 16.1 W l(-1), mean +/-
      s.e.m.; N=16) and skinned (122.6 +/- 4.6 W l(-1); N=141) fibres. Maximum relative
      power (power/F(IM) Lo, where F(IM) is maximum isometric force and Lo is standard
      fibre length) was also similar in intact (0.645 +/- 0.037; N=16) and skinned
      (0.589 +/- 0.019; N=141) fibres. Relative power is independent of volume and thus
      not subject to errors in measurement of volume. Finally, maximum isometric force
      per cross-sectional area was also found to be the same for intact and skinned
      fibres (181.9 kPa +/- 19.1; N=16; 207.8 kPa +/- 4.8; N=141, respectively). These
      results contrast with previous measurements of performance at lower temperatures
      where skinned fibres produce much less power than intact fibres from both mammals
      and non-mammalian species.

PMID- 26206355
TI  - Transient and permanent effects of suboptimal incubation temperatures on growth,
      metabolic rate, immune function and adrenocortical responses in zebra finches.
AB  - In birds, incubation temperature can vary by several degrees Celsius among nests
      of a given species. Parents may alter incubation temperature to cope with
      environmental conditions and/or to manipulate embryonic development, and such
      changes in incubation behavior could have long-lasting effects on offspring
      phenotype. To investigate short- and long-term effects of suboptimal incubation
      temperatures on survival and physiological functions in zebra finches, eggs were
      incubated at 36.2, 37.4 or 38.4  degrees C for the entire incubation period. The
      post-hatch environment was identical among the treatment groups. We found that
      hatching success was lowest in the 38.4  degrees C group, while post-hatch
      survival was lowest in the 36.2  degrees C group. Incubation temperature had sex
      specific effects on offspring phenotype: incubation temperatures affected body
      mass (Mb) but not physiological parameters of males and conversely, the
      physiological parameters but not Mb of females. Specifically, males from the 38.4
      degrees C group weighed significantly less than males from the 36.2  degrees C
      group from the nestling period to adulthood, whereas females from different
      incubation temperature groups did not differ in Mb. In contrast, females
      incubated at 36.2  degrees C had transient but significantly elevated basal
      metabolic rate and adrenocortical responses during the nestling and fledgling
      periods, whereas no treatment effect was observed in males. Innate immunity was
      not affected by incubation temperature in either sex. These results suggest that
      a 1  degrees C deviation from what is considered an optimal incubation
      temperature can lower offspring performance and offspring survival.

PMID- 26206356
TI  - The neonicotinoid clothianidin interferes with navigation of the solitary bee
      Osmia cornuta in a laboratory test.
AB  - Pollinating insects provide a vital ecosystem service to crops and wild plants.
      Exposure to low doses of neonicotinoid insecticides has sub-lethal effects on
      social pollinators such as bumblebees and honeybees, disturbing their navigation
      and interfering with their development. Solitary Hymenoptera are also very
      important ecosystem service providers, but the sub-lethal effects of
      neonicotinoids have not yet been studied well in those animals. We analyzed the
      ability of walking Osmia to remember a feeding place in a small environment and
      found that Osmia remembers the feeding place well after 4 days of training.
      Uptake of field-realistic amounts of the neonicotinoid clothianidin (0.76 ng per
      bee) altered the animals' sensory responses to the visual environment and
      interfered with the retrieval of navigational memory. We conclude that the
      neonicotinoid clothianidin compromises visual guidance and the use of
      navigational memory in the solitary bee Osmia cornuta.

PMID- 26206357
TI  - Respiratory function of the plastron in the aquatic bug Aphelocheirus aestivalis
      (Hemiptera, Aphelocheiridae).
AB  - The river bug Aphelocheirus aestivalis is a 40 mg aquatic insect that, as an
      adult, relies totally on an incompressible physical gill to exchange respiratory
      gases with the water. The gill (called a 'plastron') consists of a stationary
      layer of air held in place on the body surface by millions of tiny hairs that
      support a permanent air-water interface, so that the insect never has to renew
      the gas at the water's surface. The volume of air in the plastron is extremely
      small (0.14 mm(3)), under slightly negative pressure and connected to the gas
      filled tracheal system through spiracles on the cuticle. Here, we measure PO2 of
      the water and within the plastron gas with O2-sensing fibre optics to understand
      the effectiveness and limitations of the gas exchanger. The difference in PO2 is
      highest in stagnant water and decreases with increasing convection over the
      surface. Respiration of bugs in water-filled vials varies between 33 and 296 pmol
      O2 s(-1), depending on swimming activity. The effective thickness of the boundary
      layer around the plastron was calculated from respiration rate, PO2 difference
      and plastron surface area, according to the Fick diffusion equation and verified
      by direct measurements with the fibre-optic probes. In stagnant water, the
      boundary layer is approximately 500 MUm thick, which nevertheless can satisfy the
      demands of resting bugs, even if the PO2 of the free water decreases to half that
      of air saturation. Active bugs require thinner boundary layers (~ 100 MUm), which
      are achieved by living in moving water or by swimming.

PMID- 26206358
TI  - Variation in swim bladder drumming sounds from three doradid catfish species with
      similar sonic morphologies.
AB  - A variety of teleost fishes produce sounds for communication by vibrating the
      swim bladder with fast contracting muscles. Doradid catfishes have an elastic
      spring apparatus (ESA) for sound production. Contractions of the ESA protractor
      muscle pull the anterior transverse process of the 4th vertebra or Mullerian
      ramus (MR) to expand the swim bladder and elasticity of the MR returns the swim
      bladder to the resting state. In this study, we examined the sound
      characteristics and associated fine structure of the protractor drumming muscles
      of three doradid species: Acanthodoras cataphractus, Platydoras hancockii and
      Agamyxis pectinifrons. Despite large variations in size, sounds from all three
      species had similar mean dominant rates ranging from 91 to 131 Hz and showed
      frequencies related to muscle contraction speed rather than fish size. Sounds
      differed among species in terms of waveform shape and their rate of amplitude
      modulation. In addition, multiple distinguishable sound types were observed from
      each species: three sound types from A. cataphractus and P. hancockii, and two
      sound types from A. pectinifrons. Although sounds differed among species, no
      differences in muscle fiber fine structure were observed at the species level.
      Drumming muscles from each species bear features associated with fast
      contractions, including sarcoplasmic cores, thin radial myofibrils, abundant
      mitochondria and an elaborated sarcoplasmic reticulum. These results indicate
      that sound differences between doradids are not due to swimbladder size, muscle
      anatomy, muscle length or Mullerian ramus shape, but instead result from
      differences in neural activation of sonic muscles.

PMID- 26206359
TI  - Distinct or shared actions of peptide family isoforms: II. Multiple pyrokinins
      exert similar effects in the lobster stomatogastric nervous system.
AB  - Many neuropeptides are members of peptide families, with multiple structurally
      similar isoforms frequently found even within a single species. This raises the
      question of whether the individual peptides serve common or distinct functions.
      In the accompanying paper, we found high isoform specificity in the responses of
      the lobster (Homarus americanus) cardiac neuromuscular system to members of the
      pyrokinin peptide family: only one of five crustacean isoforms showed any
      bioactivity in the cardiac system. Because previous studies in other species had
      found little isoform specificity in pyrokinin actions, we examined the effects of
      the same five crustacean pyrokinins on the lobster stomatogastric nervous system
      (STNS). In contrast to our findings in the cardiac system, the effects of the
      five pyrokinin isoforms on the STNS were indistinguishable: they all activated or
      enhanced the gastric mill motor pattern, but did not alter the pyloric pattern.
      These results, in combination with those from the cardiac ganglion, suggest that
      members of a peptide family in the same species can be both isoform specific and
      highly promiscuous in their modulatory capacity. The mechanisms that underlie
      these differences in specificity have not yet been elucidated; one possible
      explanation, which has yet to be tested, is the presence and differential
      distribution of multiple receptors for members of this peptide family. 

PMID- 26206361
TI  - No functionally relevant mechanical effects of epimuscular myofascial connections
      between rat ankle plantar flexors.
AB  - Triceps surae muscles are mechanically connected by the shared Achilles tendon
      and by epimuscular myofascial connections. We aimed to assess the effects of
      proximal lengthening of gastrocnemius and plantaris muscles, imposed by changes
      in knee angle, on the magnitude and direction of the 3D ankle moment exerted by
      the soleus muscle and the mechanical interaction between ankle plantar flexor
      muscles during co-activation of gastrocnemius muscle, in the rat (N=9). Ankle
      angle was kept constant (90 deg), whereas knee angle was varied between 60 deg
      and 130 deg. At each knee angle, the soleus muscle was excited individually as
      well as simultaneously with the gastrocnemius muscle (SO+GA). The mathematical
      sum of individual soleus and gastrocnemius ankle moments was compared with the
      ankle moment exerted by SO+GA to assess nonlinear summation. Knee angle did not
      affect the magnitude of the soleus ankle moment (P=0.695). Moment directions in
      the transverse (P=0.050) and frontal (P=0.008) planes were affected by knee
      angle, but dissection indicated that this was not caused by length changes of the
      two-joint synergistic muscles. Nonlinear summation was found in the magnitude (
      1.4 +/- 1.9%, mean +/- s.d., P<0.001) and in the frontal plane vector direction
      of the ankle moment (0.13 +/- 0.23 deg, P=0.003); however, the extent did not
      change with knee angle. Although contraction of SO+GA increased the length of the
      Achilles tendon compared with its length at rest, this was not dependent on the
      knee angle (P=0.649). Despite the fact that intermuscular force transmission per
      se cannot be excluded, we conclude that, in vivo, the mechanical effects of
      epimuscular myofascial connections between rat ankle plantar flexors are not
      functionally relevant.

PMID- 26206360
TI  - Distinct or shared actions of peptide family isoforms: I. Peptide-specific
      actions of pyrokinins in the lobster cardiac neuromuscular system.
AB  - Although the crustacean heart is modulated by a large number of peptides and
      amines, few of these molecules have been localized to the cardiac ganglion
      itself; most appear to reach the cardiac ganglion only by hormonal routes.
      Immunohistochemistry in the American lobster Homarus americanus indicates that
      pyrokinins are present not only in neuroendocrine organs (pericardial organ and
      sinus gland), but also in the cardiac ganglion itself, where pyrokinin-positive
      terminals were found in the pacemaker cell region, as well as surrounding the
      motor neurons. Surprisingly, the single pyrokinin peptide identified from H.
      americanus, FSPRLamide, which consists solely of the conserved FXPRLamide
      residues that characterize pyrokinins, did not alter the activity of the cardiac
      neuromuscular system. However, a pyrokinin from the shrimp Litopenaeus vannamei
      [ADFAFNPRLamide, also known as Penaeus vannamei pyrokinin 2 (PevPK2)] increased
      both the frequency and amplitude of heart contractions when perfused through the
      isolated whole heart. None of the other crustacean pyrokinins tested (another
      from L. vannamei and two from the crab Cancer borealis) had any effect on the
      lobster heart. Similarly, altering the PevPK2 sequence either by truncation or by
      the substitution of single amino acids resulted in much lower or no activity in
      all cases; only the conservative substitution of serine for alanine at position 1
      resulted in any activity on the heart. Thus, in contrast to other systems
      (cockroach and crab) in which all tested pyrokinins elicit similar bioactivities,
      activation of the pyrokinin receptor in the lobster heart appears to be highly
      isoform specific. 

PMID- 26206362
TI  - Green Chemistry at the present in Korea.
AB  - OBJECTIVES: Despite the great contribution made by chemical substances to the
      development of modern civilization, their indiscriminate use has caused various
      kinds of damage to the global environment and human beings. Accordingly, the
      major developed countries and international society have tried to ensure the safe
      use of chemicals and a reduction in the use of hazardous chemicals through the
      establishment of the United Nations Environment Programme and various
      international agreements. In this reason, we tried to introduce about Green
      Chemistry progress at the present in worldwide and Korea. METHODS: We checked and
      analyzed relative journals, reports using keyword as like Green Chemistry,
      alternative chemicals, eco-friendly etc. and major country's government homepage
      search. RESULTS: Green Chemistry theory, which argues for the reduction or
      removal of harmfulness in chemicals throughout their entire life-cycle, has been
      spreading, and major developed countries, such as the US and Denmark, have
      developed and operate programs to provide reliable chemical information to help
      replace hazardous chemicals. Korea has also been conducting studies as like eco
      innovation project. Through this project the "Alternative Chemical Search
      program," has been developed, distributed, and operated since 2011 to provide
      reliable information to small and medium-sized businesses that have difficulties
      collecting information to ensure conformity to international regulations. The
      program provides information that includes the regulations of major countries and
      Korea, information on 340 alternative chemicals, 70 application cases, and 1:1
      consulting. CONCLUSIONS: The Alternative Chemical Search program is expected to
      contribute to the establishment of response systems for regulation of Korean
      small and medium-sized businesses, and it also will be used to provide basic data
      for Korean hazardous chemical regulation, together with the Act on the
      Registration and Evaluation, etc. of Chemical Substances and the Chemical Control
      act, making it possible to establish an infrastructure for Green Chemistry in
      Korea and to increase national competitiveness.

PMID- 26206363
TI  - Research on the development of green chemistry technology assessment techniques:
      a material reutilization case.
AB  - OBJECTIVES: This study presents a methodology that enables a quantitative
      assessment of green chemistry technologies. METHODS: The study carries out a
      quantitative evaluation of a particular case of material reutilization by
      calculating the level of "greenness" i.e., the level of compliance with the
      principles of green chemistry that was achieved by implementing a green chemistry
      technology. RESULTS: The results indicate that the greenness level was enhanced
      by 42% compared to the pre-improvement level, thus demonstrating the economic
      feasibility of green chemistry. CONCLUSIONS: The assessment technique established
      in this study will serve as a useful reference for setting the direction of
      industry-level and government-level technological R&D and for evaluating newly
      developed technologies, which can greatly contribute toward gaining a competitive
      advantage in the global market.

PMID- 26206364
TI  - Priority survey between indicators and analytic hierarchy process analysis for
      green chemistry technology assessment.
AB  - OBJECTIVES: This study presents the indicators and proxy variables for the
      quantitative assessment of green chemistry technologies and evaluates the
      relative importance of each assessment element by consulting experts from the
      fields of ecology, chemistry, safety, and public health. METHODS: The results
      collected were subjected to an analytic hierarchy process to obtain the weights
      of the indicators and the proxy variables. RESULTS: These weights may prove
      useful in avoiding having to resort to qualitative means in absence of weights
      between indicators when integrating the results of quantitative assessment by
      indicator. CONCLUSIONS: This study points to the limitations of current
      quantitative assessment techniques for green chemistry technologies and seeks to
      present the future direction for quantitative assessment of green chemistry
      technologies.

PMID- 26206365
TI  - Analysis of the utilization of existing test data for phase-in substance
      registration under the Act on the Registration and Evaluation, etc. of Chemical
      Substances.
AB  - OBJECTIVES: Approximately 2000 phase-in substances are subject to registration
      according to the Act on the Registration and Evaluation, etc. of Chemical
      Substances (KREACH), and the expected testing cost is 2.06 trillion Korean won
      assuming all the test data required for registration are acquired. The extent to
      which these enormous test costs can be reduced depends on the availability of
      existing data that can be used to meet the requirements of the K-REACH we
      examined the current availability of test data that can be used for chemical
      substance registration. METHODS: We analyzed the possibility of utilizing the
      existing test data obtained from 16 reference databases for 369 of 518 kinds of
      phase-in substances subject to registration that were reported in last October
      2014. RESULTS: The physical and chemical properties were available for 57.1% of
      substances, whereas data regarding human hazards and environmental hazards were
      available at considerably lower rates, 8.5% and 11.8%, respectively. CONCLUSIONS:
      Physical and chemical properties were available for a fairly high proportion,
      whereas human hazards and environmental hazards were reported for considerably
      fewer substances.

PMID- 26206366
TI  - Value of a statistical life estimation of carcinogenic chemicals for
      socioeconomic analysis in Korea.
AB  - OBJECTIVES: To protect public health from risk, the Minister of Environment in
      Korea legislated an act concerning the registration and evaluation of chemical
      substances. In this study, we estimated the value of a statistical life (VSL) of
      carcinogenic chemicals to evaluate the socioeconomic analysis in Korea. METHODS:
      The estimation of the health benefit can be calculated through an individual's
      VSL and willingness to pay (WTP). To estimate the VSL and WTP, we used a
      contingent valuation method through a web-based survey. RESULTS: The survey is
      conducted with 1434 people living in Seoul and six large cities. An analysis of
      the survey is essential to review the distribution of the characteristics of the
      target population. The statistically significant variables affecting the WTP are
      location, age, household income, quality of life. Through the review of data, we
      secured statistical validity. The WTP was estimated as 41205 Korean won
      (KRW)/person, and the estimated VSL appeared as 796 million KRW/person.
      CONCLUSIONS: There is a case in which the amount of statistical life value is
      estimated in connection with domestic environmental policy, fine dust, etc.
      However, there are no cases of evaluation for chemical. The utilization of this
      result is possible for conducting other study with chemicals.

PMID- 26206368
TI  - Assessment of quantitative structure-activity relationship of toxicity prediction
      models for Korean chemical substance control legislation.
AB  - OBJECTIVES: For successful adoption of legislation controlling registration and
      assessment of chemical substances, it is important to obtain sufficient
      toxicological experimental evidence and other related information. It is also
      essential to obtain a sufficient number of predicted risk and toxicity results.
      Particularly, methods used in predicting toxicities of chemical substances during
      acquisition of required data, ultimately become an economic method for future
      dealings with new substances. Although the need for such methods is gradually
      increasing, the-required information about reliability and applicability range
      has not been systematically provided. METHODS: There are various representative
      environmental and human toxicity models based on quantitative structure-activity
      relationships (QSAR). Here, we secured the 10 representative QSAR-based
      prediction models and its information that can make predictions about substances
      that are expected to be regulated. We used models that predict and confirm
      usability of the information expected to be collected and submitted according to
      the legislation. After collecting and evaluating each predictive model and
      relevant data, we prepared methods quantifying the scientific validity and
      reliability, which are essential conditions for using predictive models. RESULTS:
      We calculated predicted values for the models. Furthermore, we deduced and
      compared adequacies of the models using the Alternative non-testing method
      assessed for Registration, Evaluation, Authorization, and Restriction of
      Chemicals Substances scoring system, and deduced the applicability domains for
      each model. Additionally, we calculated and compared inclusion rates of
      substances expected to be regulated, to confirm the applicability. CONCLUSIONS:
      We evaluated and compared the data, adequacy, and applicability of our selected
      QSAR-based toxicity prediction models, and included them in a database. Based on
      this data, we aimed to construct a system that can be used with predicted
      toxicity results. Furthermore, by presenting the suitability of individual
      predicted results, we aimed to provide a foundation that could be used in actual
      assessments and regulations.

PMID- 26206367
TI  - The evaluation of cost-of-illness due to use of cost-of-illness-based chemicals.
AB  - OBJECTIVES: This study is conducted to estimate the cost paid by the public
      suffering from disease possibly caused by chemical and to examine the effect on
      public health. METHODS: Cost-benefit analysis is an important factor in analysis
      and decision-making and is an important policy decision tool in many countries.
      Cost-of-illness (COI), a kind of scale-based analysis method, estimates the
      potential value lost as a result of illness as a monetary unit and calculates the
      cost in terms of direct, indirect and psychological costs. This study estimates
      direct medical costs, transportation fees for hospitalization and outpatient
      treatment, and nursing fees through a number of patients suffering from disease
      caused by chemicals in order to analyze COI, taking into account the cost of
      productivity loss as an indirect cost. RESULTS: The total yearly cost of the
      diseases studied in 2012 is calculated as 77 million Korean won (KRW) per person.
      The direct and indirect costs being 52 million KRW and 23 million KRW,
      respectively. Within the total cost of illness, mental and behavioral disability
      costs amounted to 16 million KRW, relevant blood immunological parameters costs
      were 7.4 million KRW, and disease of the nervous system costs were 6.7 million
      KRW. CONCLUSIONS: This study reports on a survey conducted by experts regarding
      diseases possibly caused by chemicals and estimates the cost for the general
      public. The results can be used to formulate a basic report for a social-economic
      evaluation of the permitted use of chemicals and limits of usage.

PMID- 26206369
TI  - Study on the biodegradation of alternatives (four species including C8H8F9KO3S)
      for perfluorooctane sulfonate.
AB  - OBJECTIVES: The objective of this study was to evaluate the biodegradation
      potential of four perfluorooctane sulfonic acid (PFOS) alternatives that were
      developed at Changwon National University. While PFOS has been used widely in
      industrial and consumer products, it is known to be a persistent organic
      pollutant. Therefore, greener alternatives are highly desirable. METHODS:
      Biodegradation tests were run for 28 days using standard test protocols. The
      biochemical oxygen demand was measured daily throughout the experimental period,
      and the data were used to calculate the biodegradation rates. Microorganisms were
      isolated from the some of the tests that showed evidence of biodegradation.
      RESULTS: C8H8F9KO3S, which has the same number of carbons as the parent compound
      PFOS but a reduced number of fluorines, showed the highest biodegradation rate
      followed by C10H8F13KO3S. Chemical alternatives with lower number of carbons did
      not biodegrade readily in the experiments. CONCLUSIONS: Together, these results
      suggest that it may be advantageous to develop PFOS alternatives with 8 carbons,
      the same as PFOS, but a reduced number of fluorines; as such, chemicals are more
      susceptible to biodegradation than the parent compound.

PMID- 26206370
TI  - Green chemistry management technology in Korea.

PMID- 26206371
TI  - Reply.

PMID- 26206372
TI  - The effects of smoke derivatives on in vitro seed germination and development of
      the leopard orchid Ansellia africana.
AB  - Plant-derived smoke and smoke-isolated compounds stimulate germination in seeds
      from over 80 genera. It has also been reported that smoke affects overall plant
      vigour and has a stimulatory effect on pollen growth. The effect of smoke on
      orchid seeds, however, has not been assessed. In South Africa, orchid seeds from
      several genera may be exposed to smoke when they are released from their
      seedpods. It is therefore possible that smoke may affect their germination and
      growth. Therefore, the effects of smoke [applied as smoke-water (SW)] and two
      smoke-derived compounds, karrikinolide (KAR1 ) and trimethylbutenolide (TMB),
      were investigated on the germination and growth of orchid seeds in vitro. The
      effect of SW, KAR1 and TMB were investigated on the endangered epiphytic orchid,
      Ansellia africana, which is indigenous to tropical areas of Africa. Smoke-water,
      KAR1 and TMB were infused in half-strength MS medium. The number of germinated
      seeds and number of seeds and protocorm bodies to reach predetermined
      developmental stages were recorded on a weekly basis using a dissecting
      microscope for a 13-week period. Infusing SW 1:250 (v:v) into half-strength MS
      medium significantly increased the germination rate index (GRI) and the
      development rate index (DRI) of the A. africana seeds. All the SW treatments
      significantly increased the number of large protocorm bodies at the final stage
      of development. Infusing KAR1 into the growing medium had no significant effect
      on germination or development of the seeds. The TMB treatment, however,
      significantly reduced the GRI and DRI of A. africana seeds. 

PMID- 26206373
TI  - A process evaluation of PRONTO simulation training for obstetric and neonatal
      emergency response teams in Guatemala.
AB  - BACKGROUND: Despite expanding access to institutional birth in Guatemala,
      maternal mortality remains largely unchanged over the last ten years. Enhancing
      the quality of emergency obstetric and neonatal care is one important strategy to
      decrease mortality. An innovative, low-tech, simulation-based team training
      program (PRONTO) aims to optimize care provided during obstetric and neonatal
      emergencies in low-resource settings. METHODS: We conducted PRONTO simulation
      training between July 2012 and December 2012 in 15 clinics in Alta Verapaz,
      Huehuetenango, San Marcos, and Quiche, Guatemala. These clinics received PRONTO
      as part of a larger pair-matched cluster randomized trial of a comprehensive
      intervention package. Training participants were obstetric and neonatal care
      providers that completed pre- and post- training assessments for the two PRONTO
      training modules, which evaluated knowledge of evidence-based practice and self
      efficacy in obstetric and neonatal topics. Part of the training included a
      session for trained teams to establish strategic goals to improve clinical
      practice. We utilized a pre/post-test design to evaluate the impact of the course
      on both knowledge and self-efficacy with longitudinal fixed effects linear
      regression with robust standard errors. Pearson correlation coefficients were
      used to assess the correlation between knowledge and self-efficacy. Poisson
      regression was used to assess the association between the number of goals
      achieved and knowledge, self-efficacy, and identified facility-level factors.
      RESULTS: Knowledge and self-efficacy scores improved significantly in all areas
      of teaching. Scores were correlated for all topics overall at training
      completion. More than 60 % of goals set to improve clinic functioning and
      emergency care were achieved. No predictors of goal achievement were identified.
      CONCLUSIONS: PRONTO training is effective at improving provider knowledge and
      self-efficacy in training areas. Further research is needed to evaluate the
      impact of the training on provider use of evidence-based practices and on
      maternal and neonatal health outcomes. TRIAL REGISTRATION: NCT01653626.

PMID- 26206374
TI  - Allogenic benefit in stem cell therapy: cardiac repair and regeneration.
AB  - Stem cell (SC)-based therapies are a developing mean to repair, restore,
      maintain, or enhance organ functioning through life span. They are in particular
      a fast track to restore function in failing heart. Various types of SCs have been
      used in experimental and clinical studies showing the potential of these cells to
      revolutionize the treatment of heart diseases. Autologous cells have been
      privileged to overpass immunological barriers. The field has progressed
      tremendously and the hurdles, which have been largely overlooked in the
      excitement over the expected benefit the immunogenicity, have been revealed.
      Also, manufacturing of patient-specific clinical grade SC product, whether adult
      stem or reprogrammed induced pluripotent SCs, and the availability of these cells
      in sufficient amounts and status when needed is questionable. In contrast, adult
      SCs derived from healthy donors, thus allogeneic, have the advantage to be
      immediately available as an 'off-the-shelf' therapeutic product. The challenge is
      to overcome the immunological barriers to their transplantation. Recent research
      provided new insights into the mode of action and immune behavior of SCs in
      autologous as well as allogeneic settings. Lessons are learned and immune
      paradigms are changing: allogenicity, if balanced could be part of the dynamic
      and durable mechanisms that are critical to sustain cardiac regeneration and
      repair. We discuss the hurdles, lessons, and advances accomplished in the field
      through the progressive journey of cardiac-derived stem/progenitor cells toward
      allogeneic cardiac regenerative/reparative therapy. 

PMID- 26206375
TI  - GESPA: classifying nsSNPs to predict disease association.
AB  - BACKGROUND: Non-synonymous single nucleotide polymorphisms (nsSNPs) are the most
      common DNA sequence variation associated with disease in humans. Thus determining
      the clinical significance of each nsSNP is of great importance. Potential
      detrimental nsSNPs may be identified by genetic association studies or by
      functional analysis in the laboratory, both of which are expensive and time
      consuming. Existing computational methods lack accuracy and features to
      facilitate nsSNP classification for clinical use. We developed the GESPA (GEnomic
      Single nucleotide Polymorphism Analyzer) program to predict the pathogenicity and
      disease phenotype of nsSNPs. RESULTS: GESPA is a user-friendly software package
      for classifying disease association of nsSNPs. It allows flexibility in
      acceptable input formats and predicts the pathogenicity of a given nsSNP by
      assessing the conservation of amino acids in orthologs and paralogs and
      supplementing this information with data from medical literature. The development
      and testing of GESPA was performed using the humsavar, ClinVar and humvar
      datasets. Additionally, GESPA also predicts the disease phenotype associated with
      a nsSNP with high accuracy, a feature unavailable in existing software. GESPA's
      overall accuracy exceeds existing computational methods for predicting nsSNP
      pathogenicity. The usability of GESPA is enhanced by fast SQL-based cloud storage
      and retrieval of data. CONCLUSIONS: GESPA is a novel bioinformatics tool to
      determine the pathogenicity and phenotypes of nsSNPs. We anticipate that GESPA
      will become a useful clinical framework for predicting the disease association of
      nsSNPs. The program, executable jar file, source code, GPL 3.0 license, user
      guide, and test data with instructions are available at
      http://sourceforge.net/projects/gespa.

PMID- 26206376
TI  - Ex vivo immunosuppressive effects of mesenchymal stem cells on Crohn's disease
      mucosal T cells are largely dependent on indoleamine 2,3-dioxygenase activity and
      cell-cell contact.
AB  - INTRODUCTION: Crohn's disease (CD) is a disabling chronic enteropathy sustained
      by a harmful T-cell response toward antigens of the gut microbiota in genetically
      susceptible subjects. Growing evidence highlights the safety and possible
      efficacy of mesenchymal stem cells (MSCs) as a new therapeutic tool for this
      condition. Therefore, we aimed to investigate the effects of bone marrow-derived
      MSCs on pathogenic T cells with a view to clinical application. METHODS: T-cell
      lines from both inflamed and non-inflamed colonic mucosal specimens of CD
      patients and from healthy mucosa of control subjects were grown with the antigen
      muramyl-dipeptide in the absence or presence of donors' MSCs. The MSC effects
      were evaluated in terms of T-cell viability, apoptotic rate, proliferative
      response, immunophenotype, and cytokine profile. The role of the indoleamine 2,3
      dioxygenase (IDO) was established by adding a specific inhibitor, the 1-methyl-DL
      tryptophan, and by using MSCs transfected with the small interfering RNA (siRNA)
      targeting IDO. The relevance of cell-cell contact was evaluated by applying
      transwell membranes. RESULTS: A significant reduction in both cell viability and
      proliferative response to muramyl-dipeptide, with simultaneous increase in the
      apoptotic rate, was found in T cells from both inflamed and non-inflamed CD
      mucosa when co-cultured with MSCs and was reverted by inhibiting IDO activity and
      expression. A reduction of the activated CD4(+)CD25(+) subset and increase of the
      CD3(+)CD69(+) population were also observed when T-cell lines from CD mucosa were
      co-cultured with MSCs. In parallel, an inhibitory effect was evident on the
      expression of the pro-inflammatory cytokines tumor necrosis factor-alpha,
      interferon-gamma, interleukin-17A and -21, whereas that of the transforming
      growth factor-beta and interleukin-6 were increased, and production of the
      tolerogenic molecule soluble HLA-G was high. These latter effects were almost
      completely eliminated by blocking the IDO, whose activity was upregulated in MSCs
      co-cultured with CD T cells. The use of a semipermeable membrane partially
      inhibited the MSC immunosuppressive effects. Finally, hardly any effects of MSCs
      were observed when T cells obtained from control subjects were used. CONCLUSION:
      MSCs exert potent immunomodulant effects on antigen-specific T cells in CD
      through a complex paracrine and cell-cell contact-mediated action, which may be
      exploited for widespread therapeutic use.

PMID- 26206377
TI  - Emerging roles of nucleolar and ribosomal proteins in cancer, development, and
      aging.
AB  - Changes in nucleolar morphology and function are tightly associated with cellular
      activity, such as growth, proliferation, and cell cycle progression.
      Historically, these relationships have been extensively examined in cancer cells,
      which frequently exhibit large nucleoli and increased ribosome biogenesis. Recent
      findings indicate that alteration of nucleolar activity is a key regulator of
      development and aging. In this review, we have provided evidences that the
      nucleolus is not just a housekeeping factor but is actively involved in the
      regulation of cell proliferation, differentiation, and senescence both in vitro
      and in vivo. In addition, we have discussed how alteration of nucleolar function
      and nucleolar proteins induces specific physiological effects rather than
      widespread effects.

PMID- 26206379
TI  - The water catalysis at oxygen cathodes of lithium-oxygen cells.
AB  - Lithium-oxygen cells have attracted extensive interests due to their high
      theoretical energy densities. The main challenges are the low round-trip
      efficiency and cycling instability over long time. However, even in the state-of
      the-art lithium-oxygen cells the charge potentials are as high as 3.5 V that are
      higher by 0.70 V than the discharge potentials. Here we report a reaction
      mechanism at an oxygen cathode, ruthenium and manganese dioxide nanoparticles
      supported on carbon black Super P by applying a trace amount of water in
      electrolytes to catalyse the cathode reactions of lithium-oxygen cells during
      discharge and charge. This can significantly reduce the charge overpotential to
      0.21 V, and results in a small discharge/charge potential gap of 0.32 V and
      superior cycling stability of 200 cycles. The overall reaction scheme will
      alleviate side reactions involving carbon and electrolytes, and shed light on the
      construction of practical, rechargeable lithium-oxygen cells. 

PMID- 26206380
TI  - A facultative endosymbiont in aphids can provide diverse ecological benefits.
AB  - Ecologically important traits of insects are often affected by facultative
      bacterial endosymbionts. This is best studied in the pea aphid Acyrthosiphon
      pisum, which is frequently infected by one or more of eight facultative symbiont
      species. Many of these symbiont species have been shown to provide one ecological
      benefit, but we have little understanding of the range of effects that a single
      strain can have. Here, we describe the phenotypes conferred by three strains of
      the recently discovered bacterium known as X-type (Enterobacteriaceae), each in
      their original aphid genotype which also carries a Spiroplasma symbiont. All
      comparisons are made between aphids that are coinfected with Spiroplasma and X
      type and aphids of the same genotype that harbour only Spiroplasma. We show that
      in all cases, infection with X-type protects aphids from the lethal fungal
      pathogen Pandora neoaphidis, and in two cases, resistance to the parasitoid
      Aphidius ervi also increases. X-type can additionally affect aphid stress
      responses--the presence of X-type increased reproduction after the aphids were
      heat-stressed. Two of the three strains of X-type are able to provide all of
      these benefits. Under benign conditions, the aphids tended to suffer from reduced
      fecundity when harbouring X-type, a mechanism that might maintain intermediate
      frequencies in field populations. These findings highlight that a single strain
      of a facultative endosymbiont has the potential to provide diverse benefits to
      its aphid host.

PMID- 26206381
TI  - Hemodynamic changes in the prefrontal cortex during working memory in essential
      hypertension.
AB  - Behavioral performance and hemodynamic changes in the prefrontal cortex (PFC)
      represent cerebrovascular reserve and may indicate functional deficits related to
      essential hypertension. Fifteen stage 1 hypertensive and normotensive males (19
      55 years) were compared on four tests of working memory (digit span and auditory
      consonant trigrams), and accompanying hemodynamic changes measured by functional
      near infrared spectroscopy (fNIRS). With participants blindfolded, the four tests
      were randomized while fNIRS was used to monitor bilateral PFC changes in
      oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb), total hemoglobin (tHb), and
      hemoglobin difference. The hypertensive group demonstrated significant impairment
      in performance on the working memory tests with a trend of decreased efficiency
      performance scores (tests score/O2Hb and tHb changes). Significant correlations
      were noted in the hypertensive group between test performance and changes in O2Hb
      and tHb in both the left and right PFC. These findings suggest that fNIRS
      combined with cognitive testing may provide important measures of cerebrovascular
      reserve in essential hypertension. 

PMID- 26206382
TI  - Erratum to: The role of the dorsal hippocampus in two versions of the touchscreen
      automated paired associates learning (PAL) task for mice.

PMID- 26206378
TI  - p53 regulates cytoskeleton remodeling to suppress tumor progression.
AB  - Cancer cells possess unique characteristics such as invasiveness, the ability to
      undergo epithelial-mesenchymal transition, and an inherent stemness. Cell
      morphology is altered during these processes and this is highly dependent on
      actin cytoskeleton remodeling. Regulation of the actin cytoskeleton is,
      therefore, important for determination of cell fate. Mutations within the TP53
      (tumor suppressor p53) gene leading to loss or gain of function (GOF) of the
      protein are often observed in aggressive cancer cells. Here, we highlight the
      roles of p53 and its GOF mutants in cancer cell invasion from the perspective of
      the actin cytoskeleton; in particular its reorganization and regulation by cell
      adhesion molecules such as integrins and cadherins. We emphasize the multiple
      functions of p53 in the regulation of actin cytoskeleton remodeling in response
      to the extracellular microenvironment, and oncogene activation. Such an approach
      provides a new perspective in the consideration of novel targets for anti-cancer
      therapy.

PMID- 26206383
TI  - Efficient Self-Assembly of Di-, Tri-, Tetra-, and Hexavalent Hosts with
      Predefined Geometries for the Investigation of Multivalency.
AB  - Coordination-driven self-assembly of differently shaped di- to hexavalent crown
      ether host molecules is described. A series of [21]crown-7- and [24]crown-8
      substituted bipyridine and terpyridine ligands was synthetized in a "toolbox"
      approach. Subsequent coordination to 3d transition metal and ruthenium(II) ions
      provides an easy and fast access to host assemblies with variable valency and pre
      defined orientations of the crown-ether moieties. Preliminary isothermal
      calorimetry (ITC) titrations provided promising results, which indicated the host
      complexes under study to be suitable for the future investigation of multivalent
      and cooperative binding. The hosts described herein will also be suitable for the
      construction of various multiply threaded mechanically interlocked molecules. 

PMID- 26206384
TI  - Multitarget fluorescence in situ hybridization assay for the detection of lung
      cancer in bronchial cytology specimens: A Comparison With Routine Cytology.
AB  - BACKGROUND: Routine bronchial cytology is an important diagnostic tool in
      suspected lung cancer. The purpose of this study is to evaluate the performance
      of LAVysion FISH assay over routine cytology for the detection of malignant
      bronchial cytology specimens. METHODS: Forty six patients who underwent
      bronchoscopic examination in a period of 6 months were included. Bronchial
      brushing and/or washing specimens were accompanied by concurrent endobronchial
      biopsy and/or FNA, which were used as gold standard for diagnosis. The smears for
      FISH assay were made from the discarded residual fluid after being processed for
      routine cytology. RESULTS: Twenty seven of the 46 patients were diagnosed of
      malignancy. For bronchial brushing specimens, the sensitivity of routine cytology
      and FISH for the detection of malignancy was 18% (3/17) and 35% (6/17)
      respectively (p = 0.08); the specificity of routine cytology and FISH was the
      same, 80% (8/10). For bronchial washing specimens, the sensitivity of routine
      cytology and FISH for the detection of malignancy was 8% (2/24) and 29% (7/24)
      respectively (p = 0.01); the specificity of routine cytology and FISH was the
      same, 94% (16/17). CONCLUSIONS: Our data shows that routine bronchial cytology
      appears to have a very low sensitivity for the detection of malignancy. FISH
      assay appears to increase the sensitivity for the detection of malignancy, but
      does not appear to improve it to a desirable level. A larger prospective study is
      necessary to further evaluate the role of FISH assay in the detection of
      malignancy in bronchial cytology specimens.

PMID- 26206385
TI  - Training specialists to write appropriate reply letters to general practitioners
      about patients with medically unexplained physical symptoms; A cluster-randomized
      trial.
AB  - OBJECTIVE: To evaluate effects of a communication training for specialists on the
      quality of their reply letters to general practitioners (GPs) about patients with
      medically unexplained physical symptoms (MUPS). METHODS: Before randomization,
      specialists included <=3 MUPS patients in a multi-center cluster-randomized
      trial. In 14h of MUPS-specific communication training, 2.5h focused on reply
      letters. Letters were discussed with regard to reporting and answering GPs'
      referral questions and patients' questions, and to reporting findings, explaining
      MUPS with perpetuating factors and giving advice. After the training, all doctors
      again included <=3 MUPS patients. Reply letters to GPs were assessed for quality
      and blindly rated on a digital scale. RESULTS: We recruited 478 MUPS patients and
      123 specialists; 80% of the doctors wrote >=1 reply letters, 285 letters were
      assessed. Trained doctors reported (61% versus 37%, OR=2.55, F(1281)=6.60,
      p(group*time)=.01) and answered (63% versus 33%, OR=3.31, F(1281)=5.36,
      p(group*time)=.02) patients' questions more frequently than untrained doctors.
      CONCLUSION: Training improves reply letters with regard to patients' questions,
      but not with regard to the following: GPs' referral questions, somatic findings,
      additional testing, explaining, and advice. PRACTICE IMPLICATIONS: Training
      specialists to write appropriate reply letters needs more focus on explanation
      and advice.

PMID- 26206386
TI  - Impact of bacterial contamination of the abdominal cavity during
      pancreaticoduodenectomy on surgical-site infection.
AB  - BACKGROUND: Several risk factors for complications after pancreaticoduodenectomy
      have been reported. However, the impact of intraoperative bacterial contamination
      on surgical outcome after pancreaticoduodenectomy has not been examined in depth.
      METHODS: This retrospective study included patients who underwent
      pancreaticoduodenectomy and peritoneal lavage using 7000 ml saline between July
      2012 and May 2014. The lavage fluid was subjected to bacterial culture
      examination. The influence of a positive bacterial culture on surgical-site
      infection (SSI) and postoperative course was evaluated. Risk factors for positive
      bacterial cultures were also evaluated. RESULTS: Forty-six (21.1 per cent) of 218
      enrolled patients had a positive bacterial culture of the lavage fluid.
      Incisional SSI developed in 26 (57 per cent) of these 46 patients and in 13 (7.6
      per cent) of 172 patients with a negative lavage culture (P < 0.001). Organ/space
      SSI developed in 32 patients with a positive lavage culture (70 per cent) and in
      43 of those with a negative culture (25.0 per cent) (P < 0.001). Grade B/C
      pancreatic fistula was observed in 22 (48 per cent) and 48 (27.9 per cent)
      respectively of patients with positive and negative lavage cultures (P = 0.010).
      Postoperative hospital stay was longer in patients with a positive lavage culture
      (28 days versus 21 days in patients with a negative culture; P = 0.028).
      Multivariable analysis revealed that internal biliary drainage, combined
      colectomy and a longer duration of surgery were significant risk factors for
      positive bacterial culture of the lavage fluid. CONCLUSION: Intraoperative
      bacterial contamination has an adverse impact on the development of SSI and grade
      B/C pancreatic fistula following pancreaticoduodenectomy.

PMID- 26206388
TI  - Noncompaction in mitochondrial trifunctional protein deficiency due to a HADHB
      mutation.

PMID- 26206387
TI  - Early fluid overload is associated with acute kidney injury and PICU mortality in
      critically ill children.
AB  - Fluid overload (FO) has been associated with an increased risk for adverse
      outcomes in critically ill patients. Information on the impact of FO on mortality
      in a general population of pediatric intensive care unit (PICU) is limited. We
      aimed to determine the association of early FO with the development of acute
      kidney injury (AKI) and mortality during PICU stay and evaluate whether early FO
      predicts mortality, even after adjustment for illness severity assessed by
      pediatric risk of mortality (PRISM) III. This prospective study enrolled 370
      critically ill children. The early FO was calculated based on the first 24-h
      total of fluid intake and output after admission and defined as cumulative fluid
      accumulation >=5% of admission body weight. Of the patients, 64 (17.3 %)
      developed early FO during the first 24 h after admission. The PICU mortality rate
      of the whole cohort was 18 of 370 (4.9%). The independent factors significantly
      associated with early FO were PRISM III, age, AKI, and blood bicarbonate level.
      The early FO was associated with AKI (odds ratio [OR] = 1.34, p < 0.001) and
      mortality (OR = 1.36, p < 0.001). The association of early FO with mortality
      remained significant after adjustment for potential confounders including AKI and
      illness severity. The area under the receiver operating characteristic curve
      (AUC) of early FO for predicting mortality was 0.78 (p < 0.001). This result,
      however, was not better than PRISM III (AUC = 0.85, p < 0.001). CONCLUSION: Early
      FO was associated with increased risk for AKI and mortality in critically ill
      children. WHAT IS KNOWN: Fluid overload is associated with an increased risk for
      adverse outcomes in specific clinical settings of pediatric population. What is
      New: Early fluid overload during the first 24 h after PICU admission is
      independently associated with increased risk for acute kidney injury and
      mortality in critically ill children.

PMID- 26206389
TI  - In Memoriam of Prof. Bernard Witholt.

PMID- 26206390
TI  - Chemical analysis of fish bile extracts for monitoring endocrine disrupting
      chemical exposure in water: Bisphenol A, alkylphenols, and norethindrone.
AB  - The present study determined concentrations of estrogenic bisphenol A (BPA),
      nonylphenol, octylphenol (4-tert-octylphenol), butylphenol (4-tert-butylphenol),
      and progestogenic norethindrone by liquid chromatography-tandem mass spectrometry
      in bile extracts from field fish from the Xin'an River and market fish in
      Shanghai, China. Compared with the field fish, endocrine disrupting chemical
      (EDC) concentrations in market fish bile were at relatively high levels with high
      detectable rates. The average concentrations of BPA, nonylphenol, 4-tert
      octylphenol, 4-tert-butylphenol, and norethindrone in field fish bile were 30.1
      ug/L, 203 ug/L, 4.69 ug/L, 7.84 ug/L, and 0.514 ug/L, respectively; in market
      fish bile they were 240 ug/L, 528 ug/L, 76.5 ug/L, 12.8 ug/L, and 5.26 ug/L,
      respectively; and in the surface water of Xin'an River they were 38.8 ng/L, 7.91
      ng/L, 1.98 ng/L, 2.66 ng/L, and 0.116 ng/L, respectively. The average of total
      estrogenic activity of river water was 3.32 ng/L estradiol equivalents. High
      bioconcentration factors (BCFs) were discovered for all 5 EDCs (?998-fold) in
      field fish bile. Furthermore, the authors analyzed the BCF value of BPA in fish
      bile after 30-d exposure to environmentally relevant concentrations of BPA in the
      laboratory, and the analysis revealed that BCF in fish bile (BCF(Fish bile))
      changed in an inverse concentration-dependent manner based on the log10
      transformed BPA concentration in water. Strikingly, the data from the field study
      were well fitted within this trend. The data together suggested that analysis of
      fish bile extracts could be an efficient method for assessing waterborne EDCs
      exposure for aquatic biota.

PMID- 26206391
TI  - Sex-Cord Stromal Tumors in Children and Teenagers: Results of the TGM-95 Study.
AB  - BACKGROUND: We present the results of the TGM-95 study for gonadal sex-cord
      stromal tumors (SCT). METHODS: Between 1995 and 2005, children (<18 years) with
      gonadal SCT were prospectively registered. Primary gonadal resection was
      recommended whenever feasible. Patients with disseminated disease or an
      incomplete resection received neoadjuvant or adjuvant VIP chemotherapy
      (etoposide, ifosfamide, cisplatinum). RESULTS: Thirty-eight children with ovarian
      SCT were registered. Median age was 10.7y. Endocrine symptoms were present in 21
      cases. The histological diagnoses were as follows: juvenile (23) and adult (3)
      granulosa cell tumors, Sertoli-Leydig cell tumors (11), and mixed germ cell SCT
      (1). An initial oophorectomy +/- salpingectomy led to complete resection in 23
      patients who did not receive adjuvant treatment; two of them relapsed: one
      achieved second complete remission whereas the other one died of disease. Fifteen
      patients had tumor rupture and/or malignant ascites: 11 received chemotherapy and
      did not relapse, four did not receive chemotherapy and relapsed with a fatal
      outcome in two cases. With a median follow-up of 5.9y, the 5-y EFS and OS rates
      were respectively 85% and 94%. Eleven patients had localized testicular tumors
      (median age 0.83y): juvenile granulosa cell tumors (4), Sertoli or Leydig cell
      tumors (5) and not otherwise specified SCT (2). Treatment was surgery alone with
      an inguinal orchiectomy. None have relapsed (median follow-up: 5.4y).
      CONCLUSIONS: Childhood SCT carry favorable prognosis. In ovarian SCT, surgery
      should be complete and non-mutilating. Adjuvant chemotherapy efficiently prevents
      recurrences in cases of tumor rupture. In childhood testicular SCT, the prognosis
      is excellent with an inguinal orchiectomy, prompting the debate on testis-sparing
      surgery.

PMID- 26206392
TI  - Fatiguing exercise initiated later in life reduces incidence of fibrillation and
      improves sleep quality in Drosophila.
AB  - As the human body ages, the risk of heart disease and stroke greatly increases.
      While there is evidence that lifelong exercise is beneficial to the heart's
      health, the effects of beginning exercise later in life remain unclear. This
      study aimed to investigate whether exercise training started later in life is
      beneficial to cardiac aging in Drosophila. We examined 4-week-old wild-type
      virgin female flies that were exposed to exercise periods of either 1.5, 2.0, or
      2.5 h per day, 5 days a week for 2 weeks. Using M-mode traces to analyze cardiac
      function by looking at parameters including heart rate, rhythmicity, systolic and
      diastolic diameter, and interval and fractional shortening, we found that cardiac
      function declined with age, shown by an increase in the number of fibrillation
      events and a decrease in fractional shortening. About 2.0 and 2.5 h of exercise
      per day displayed a reduced incidence of fibrillation events, and only physical
      exercise lasting 2.5-h period increased fractional shortening and total sleep
      time in Drosophila. These data suggested that training exercise needs to be
      performed for longer duration to exert physiological benefits for the aging
      heart. Additionally, climbing ability to assess the exercise-induced muscle
      fatigue was also measured. We found that 2.0 and 2.5 h of exercise caused
      exercise-induced fatigue, and fatiguing exercise is beneficial for cardiac and
      healthy aging overall. This study provides a basis for further study in humans on
      the impact of beginning an exercise regimen later in life on cardiac health.

PMID- 26206393
TI  - Electric-field-induced Spontaneous Magnetization and Phase Transitions in Zigzag
      Boron Nitride Nanotubes.
AB  - We demonstrate an alternative scheme for realizing spin polarizations in
      semiconductor nanostructures by an all-electric way. The electronic and magnetic
      properties of the model system, zigzag pristine boron nitride nanotubes (BNNTs),
      are investigated under a transverse electric field (E) through spin-polarized
      density functional theory calculations. As E increases, the band gap of BNNTs is
      reduced due to charge redistribution induced by the asymmetry of electrostatic
      potential energy, and BNNTs experience rich phase transitions, such as
      semiconductor-metal transition and nonmagnetic (NM) metal-ferromagnetic (FM)
      metal transitions. Electric-field-induced magnetization occurs when a
      sufficiently high density of states at the Fermi level in the vicinity of metal
      insulator transition is reached due to the redistribution of electronic bands and
      charge transferring across the BNNTs. Further analysis show that the spontaneous
      magnetization is derived from the localized nature of the 2p states of B and N,
      and the ferromagnetic coupling is stabilized by Zener's double-exchange
      mechanism. Our results may provide a viable way to realize spintronic devices for
      applications. 

PMID- 26206394
TI  - Utilizing the anti-ferromagnetic functionality of a multiferroic shell to study
      exchange bias in hybrid core-shell nanostructures.
AB  - A three-step method has been employed to synthesize 1D core-shell nanostructures
      consisting of a ferromagnetic Co90Pt10 (CoPt) core and a La doped multiferroic
      Bi0.87La0.13FeO3 (BLFO) shell. La doping efficiently removes the secondary
      impurity phases in the multiferroic shell and exchange interaction gives a
      significant exchange bias effect demonstrating the anti-ferromagnetic
      functionality of Bi0.87La0.13FeO3. 

PMID- 26206396
TI  - Hazard banding in compliance with the new Globally Harmonised System (GHS) for
      use in control banding tools.
AB  - Many control banding tools use hazard banding in risk assessments for the
      occupational handling of hazardous substances. The outcome of these assessments
      can be combined with advice for the required risk management measures (RMMs). The
      Globally Harmonised System of Classification and Labelling of Chemicals (GHS) has
      resulted in a change in the hazard communication elements, i.e. Hazard (H)
      statements instead of Risk-phrases. Hazard banding schemes that depend on the old
      form of safety information have to be adapted to the new rules. The purpose of
      this publication is to outline the rationales for the assignment of hazard bands
      to H statements under the GHS. Based on this, this publication proposes a hazard
      banding scheme that uses the information from the safety data sheets as the basis
      for assignment. The assignment of hazard bands tiered according to the severity
      of the underlying hazards supports the important principle of substitution.
      Additionally, the set of assignment rules permits an exposure-route-specific
      assignment of hazard bands, which is necessary for the proposed route-specific
      RMMs. Ideally, all control banding tools should apply the same assignment rules.
      This GHS-compliant hazard banding scheme can hopefully help to establish a
      unified hazard banding strategy in the various control banding tools. 

PMID- 26206397
TI  - Changes in difficult airway predictors following mandibular setback surgery.
AB  - The aim of this study was to determine the effect of surgical mandibular backward
      movements on the predictors of a difficult airway. Thirty-seven skeletal class
      III patients were included in this study. The Mallampati score, body mass index
      (BMI), maximal inter-incisal distance, and thyromental and sternomental distances
      of these patients were evaluated preoperatively and at 6 months and 2 years
      postoperatively. A sagittal split ramus osteotomy (SSRO) without genioplasty was
      performed in all patients by the same surgical team, and anaesthesia was provided
      by the same anaesthesiologist using nasotracheal intubation. The paired samples t
      test and Wilcoxon signed-rank test were used for statistical comparisons of the
      data. There were no statistically significant changes in BMI or sternomental and
      thyromental distances after SSRO. The maximal inter-incisal distance was
      significantly reduced at 6 months postoperatively (P<0.05), but no statistical
      difference was found between the values obtained preoperatively and at 2 years
      postoperative. A statistically significant increase in Mallampati score was
      observed postoperatively (P<0.05). Both the patient and practitioner should be
      aware of the risks associated with an increased postoperative Mallampati score in
      mandibular setback patients. The amount of mandibular setback in skeletal class
      III patients with a high preoperative Mallampati score should be limited to
      prevent potential postoperative airway problems. 

PMID- 26206395
TI  - Brazilian green propolis induced apoptosis in human lung cancer A549 cells
      through mitochondrial-mediated pathway.
AB  - OBJECTIVES: Propolis effect on the growth and apoptosis of human lung
      adenocarcinoma (A549 cells) was investigated as well as its mechanisms. METHODS:
      Cells were incubated with propolis for 72 h, and 3-(4,5- dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were employed to
      assess cell viability and the inhibitory concentration (IC). Apoptosis was
      detected by Acridine Orange/Ethidium Bromide and 4',6-diamidino-2-phenylindole
      staining after 24 and 48 h of incubation with 1/4 IC50 of propolis by testing the
      mitochondrial membrane potential (DeltaPsim) and the expression of apoptosis
      related genes (p53, Caspase-3, Bax, Bcl-2, Bcl-XL , Noxa, Puma and p21) by
      reverse transcription polymerase chain reaction. KEY FINDINGS: Propolis displayed
      antiproliferative and cytotoxic effects on A549 cells in a dose- and time
      dependent manner, but it did not suppress the growth of normal Vero cells. An
      enhanced apoptosis was seen in A549 propolis-treated cells after 48 h compared
      with the control cells. Propolis decreased mitochondrial membrane potential by
      overexpression of pro-apoptotic genes (Bax and Noxa) and reduction of the
      antiapoptotic gene Bcl-XL . The expression level of other genes remained
      unchanged (p53, Caspse-3 and Bax), whereas p21 expression was increased. Propolis
      induced caspase-independent apoptosis through a p53-independent mitochondrial
      pathway, and cell cycle arrest by upregulation of p21. CONCLUSIONS: Although
      propolis induces apoptosis mainly by p53-independent manner, it may be induced by
      another pathway, and new insights may arise for preventing or treating lung
      cancer.

PMID- 26206398
TI  - Treatment of the distal fracture in radioulna based on the volar wrist dual
      channel approach and postoperative X-ray diagnosis.
AB  - The fracture of the distal ulna and radius is a kind of fracture that results in
      high morbidity and occurrence rate and contributes to about one-sixth of the
      entire body's fracture. In this study, we implemented the improved palmar wrist
      surgery by a volar wrist dual channel approach. Between 2011 and 2014, we have
      treated 67 distal radius fracture patients. We divided them into two parts
      randomly, and treat them by the Carpometacarpal direct approach solution and dual
      wrist palmar surgical approach solution respectively. After the surgery, the
      differences in the incidence of median nerve irritation are significant (P <
      0.01). With reference to the exposure time of fracture, the operation time and
      the pronator quadratus muscle repair rate, we find that the exposure time of
      fracture and the operation time in the dual wrist palmar surgical approach
      solution are much less than that as compared to the Carpometacarpal direct
      approach solution (P < 0.01). The improved dual wrist palmar surgical approach
      can lead to a successful treatment of the distal radius fractures volar distal
      radial ulnar by reducing the blind exposure problem. As such, the surgeon can
      complete treatment of fractures of the region under direct vision during
      operation. Furthermore, reducing the median nerve in the carpal tunnel and the
      structure of the stretch can decrease the incidence of postoperative
      complications. Postoperative X-ray diagnosis is then performed to examine the
      patients' recovery and assist in clinical follow-up. Our study proves that the
      volar wrist dual channel approach can be successfully achieved by a surface
      incision surgical implementation of the dual channel, and gives rise to a
      minimally invasive operation. 

PMID- 26206399
TI  - Age and sex-specific relationships between blood pressure variability and carotid
      intima-media thickness.
AB  - This study evaluated the association between carotid intima-media thickness (IMT)
      and 24 h ambulatory blood pressure variability (BPV) in 150 subjects. The
      subjects were divided into different age groups and gender groups. We found that
      for the subjects aged less than 45 years, 24 h and daytime diastolic BPV were
      associated with the increased IMT (r = 0.525, P = 0.018; r = 0.507, P = 0.022).
      For the middle aged people (46-55 years), daytime (r = 0.377, P = 0.014) and 24 h
      systolic BPV (r = 0.366, P = 0.017) were more related to the increases in IMT
      than 24 h diastolic BPV (r = 0.320, P = 0.039). However, no association between
      carotid IMT and BPV was found in the elderly (>55 years). In addition, the
      relationships between carotid IMT and BPV were more obvious in males than
      females. 24 h systolic BPV (P = 0.008) is the independent factor to evaluate the
      increased carotid IMT for males, but not for females. The findings in our study
      indicated that age and sex had influences on progression of carotid IMT. We
      conclude that the relationship between carotid IMT and ambulatory BPV can be
      modified by age and sex, thus, the regression model using BPV to evaluate the
      arteriosclerotic progression should take age and sex into account.

PMID- 26206400
TI  - Hidden pattern discovery on epileptic EEG with 1-D local binary patterns and
      epileptic seizures detection by grey relational analysis.
AB  - This paper proposes a novel approach to detect epilepsy seizures by using
      Electroencephalography (EEG), which is one of the most common methods for the
      diagnosis of epilepsy, based on 1-Dimension Local Binary Pattern (1D-LBP) and
      grey relational analysis (GRA) methods. The main aim of this paper is to evaluate
      and validate a novel approach, which is a computer-based quantitative EEG
      analyzing method and based on grey systems, aimed to help decision-maker. In this
      study, 1D-LBP, which utilizes all data points, was employed for extracting
      features in raw EEG signals, Fisher score (FS) was employed to select the
      representative features, which can also be determined as hidden patterns.
      Additionally, GRA is performed to classify EEG signals through these Fisher
      scored features. The experimental results of the proposed approach, which was
      employed in a public dataset for validation, showed that it has a high accuracy
      in identifying epileptic EEG signals. For various combinations of epileptic EEG,
      such as A-E, B-E, C-E, D-E, and A-D clusters, 100, 96, 100, 99.00 and 100% were
      achieved, respectively. Also, this work presents an attempt to develop a new
      general-purpose hidden pattern determination scheme, which can be utilized for
      different categories of time-varying signals.

PMID- 26206401
TI  - Factors governing long-term adherence to a gluten-free diet in adult patients
      with coeliac disease.
AB  - BACKGROUND: A strict gluten-free diet is the cornerstone of treatment for coeliac
      disease. Studies of gluten-free diet adherence have rarely used validated
      instruments. There is a paucity of data on long-term adherence to the gluten-free
      diet in the adult population. AIMS: To determine the long-term adherence to the
      gluten-free diet and potential associated factors in a large coeliac disease
      referral centre population. METHODS: We performed a mailed survey of adults with
      clinically, serologically and histologically confirmed coeliac disease diagnosed
      >=5 years prior to survey. The previously validated Celiac Disease Adherence Test
      was used to determine adherence. Demographic, socio-economic and potentially
      associated factors were analysed with adherence as the outcome. RESULTS: The
      response rate was 50.1% of 709 surveyed, the mean time on a gluten-free diet 9.9
      +/- 6.4 years. Adequate adherence (celiac disease adherence test score <13) was
      found in 75.5% of respondents. A higher level of education was associated with
      adequate adherence (P = 0.002) even after controlling for household income (P =
      0.0220). Perceptions of cost, effectiveness of the gluten-free diet, knowledge of
      the gluten-free diet and self-effectiveness at following the gluten-free diet
      correlated with adherence scores (P < 0.001). CONCLUSIONS: Long-term adherence to
      a gluten-free diet was adequate in >75% of respondents. Perceived cost remains a
      barrier to adherence. Perceptions of effectiveness of gluten-free diet as well as
      its knowledge, are potential areas for intervention.

PMID- 26206402
TI  - Solid-State Characterization and Interconversion of Recrystallized Amodiaquine
      Dihydrochloride in Aliphatic Monohydric Alcohols.
AB  - Amodiaquine dihydrochloride monohydrate (AQ-DM) was obtained by recrystallizing
      amodiaquine dihydrochloride dihydrate (AQ-DD) in methanol, ethanol, and n
      propanol. Solid-state characterization of AQ-DD and AQ-DM was performed using X
      ray powder diffractometry, Fourier transform infrared spectroscopy,
      thermogravimetry, and differential scanning calorimetry. All recrystallized
      samples were identified as AQ-DM. Crystal habits of AQ-DD and AQ-DM were shown to
      be needle-like and rhombohedral crystals, respectively. When AQ-DD and AQ-DM were
      exposed to various relative humidity in dynamic vapor sorption apparatus, no
      solid-state interconversion was observed. However, AQ-DM showed higher solubility
      than AQ-DD when exposed to bulk water during solubility study, while excess AQ-DM
      was directly transformed back to a more stable AQ-DD structure. Heating AQ-DM
      sample to temperatures >=190 degrees C induced initial change to metastable
      amorphous form (AQ-DA) which was rapidly recrystallized to AQ-DD upon >=80%RH
      moisture exposure. AQ-DD was able to be recrystallized in alcohols (C1-C3) as AQ
      DM solid-state structure. In summary, AQ-DM was shown to have different
      solubility, moisture and temperature stability, and interconversion pathways when
      compared to AQ-DD. Thus, when AQ-DM was selected for any pharmaceutical
      applications, these critical transformation and property differences should be
      observed and closely monitored.

PMID- 26206403
TI  - Development of an Abuse- and Alcohol-Resistant Formulation Based on Hot-Melt
      Extrusion and Film Coating.
AB  - This study focused on the development of flexible (i.e., deformable) multiple
      unit pellets that feature (i) a prolonged drug release, (ii) drug abuse
      deterrence, and (iii) a minimal risk of alcohol-induced dose dumping (ADD).
      Deformable pellets were prepared via an advanced continuous one-step hot-melt
      extrusion (HME) technique, with the drug (i.e., antipyrine and codeine phosphate)
      fed as an aqueous solution into the molten matrix material (i.e., cornstarch, gum
      arabic, and xanthan). Formulations that had suitable mechanical characteristics
      (i.e., high compression strength) were coated with a flexible Aquacoat((r)) ARC
      film to ensure prolonged release and to avoid ADD. The pellets were characterized
      in terms of their mechanical properties and in vitro drug release behavior in
      alcoholic media. All formulations were abuse deterrent: they had a high
      compression strength and grinding the pellets into powder was impossible. Since
      the pellets comprising gum arabic and xanthan as a matrix did not remain intact
      during dissolution testing, they had a very fast drug release rate. Cornstarch
      based pellets that swelled but remained intact in the dissolution media had a
      slower drug release. Coated cornstarch-based pellets had a prolonged release over
      8 h and resistance to dose dumping in 20 and 40% ethanol. Our results indicate
      that cornstarch-based pellets manufactured via the advanced HME process followed
      by coating are a promising formulation that makes tampering difficult due to a
      high compression strength combined with robustness in alcoholic media. 

PMID- 26206404
TI  - A deeper insight into strain for the sila-bi[6]prismane ( Si18H12) cluster with
      its endohedrally trapped silicon atom, Si19H12.
AB  - A new family of over-coordinated hydrogenated silicon nanoclusters with
      outstanding optical and mechanical properties has recently been proposed. For one
      member of this family, namely the highly symmetric Si19 H12 nanocrystal, strain
      calculations have been presented with the goal to question its thermal stability
      and the underlying mechanism of ultrastability and electron-deficiency
      aromaticity. Here, the invalidity of these strain energy (SE) calculations is
      demonstrated mainly based on a fundamentally wrong usage of homodesmotic
      reactions, the miscounting of atomic bonds, and arithmetic errors. Since the
      article in question is entirely anchored on those erroneous SE values, all of its
      conclusions and predictions become without meaning. We provide evidence here that
      the nanocrystal in question suffers from such low levels of strain that its
      thermodynamical stability should be largely sufficient for device fabrication in
      a realistic plasma reactor. Most remarkably, the two "alternative," irregular
      isomers explicitly proposed in the aforementioned article are also electron
      deficient, nontetrahedral, ultrastable, and aromatic nicely underlining the
      universality of the ultrastability concept for nanometric hydrogenated silicon
      clusters.

PMID- 26206405
TI  - The surgery of the long-term central venous accesses in oncology.
AB  - The implantation of Long-Term Central Venous Catheters (LTCVC) in cancer patients
      has been essential to conduct the oncological treatments of today. The complexity
      of the protocols requires accuracy on the management of such devices in order to
      keep them long-functioning. The article focuses on such subject from an
      oncological perspective, pointing out threats of the disease to the central
      venous system (CVS) and the ways to face them successfully. The most salient
      points related to surgical techniques and the insights to follow-up long-term
      inserted catheters are discussed. An anatomical classification is suggested to
      help understand occurrence of malpositions and to north the necessary maneuvers
      of repositioning. Such matters are based on 3000 LTCVC-placements performed by
      the author at the Brazilian National Cancer Institute (INCA) between 1999 and
      2011. As nearly 30% of the patients presented some sort of anatomical disorder at
      the moment of the surgery, it was judged worthy to address such experience to
      those young surgical oncologists willing to tackle LTCVCs in Cancer Units. 

PMID- 26206406
TI  - Breast cancer detection and classification in digital mammography based on Non
      Subsampled Contourlet Transform (NSCT) and Super Resolution.
AB  - Breast cancer is one of the most perilous diseases among women. Breast screening
      is a method of detecting breast cancer at a very early stage which can reduce the
      mortality rate. Mammography is a standard method for the early diagnosis of
      breast cancer. In this paper, a new algorithm is proposed for breast cancer
      detection and classification in digital mammography based on Non-Subsampled
      Contourlet Transform (NSCT) and Super Resolution (SR). The presented algorithm
      includes three main parts including pre-processing, feature extraction and
      classification. In the pre-processing stage, after determining the region of
      interest (ROI) by an automatic technique, the quality of image is improved using
      NSCT and SR algorithm. In the feature extraction part, several features of the
      image components are extracted and skewness of each feature is calculated.
      Finally, AdaBoost algorithm is used to classify and determine the probability of
      benign and malign disease. The obtained results on Mammographic Image Analysis
      Society (MIAS) database indicate the significant performance and superiority of
      the proposed method in comparison with the state of the art approaches. According
      to the obtained results, the proposed technique achieves 91.43% and 6.42% as a
      mean accuracy and FPR, respectively. 

PMID- 26206407
TI  - Novel approach to pleurodesis with 50 % glucose for air leakage after lung
      resection or pneumothorax.
AB  - PURPOSE: Pleurodesis is performed in patients demonstrating air leakage after
      lung resection and in those with pneumothorax who must avoid surgery. However,
      there have so far been very few reports of pleurodesis with 50 % glucose. We
      herein examined the feasibility and effectiveness of this novel pleurodesis
      technique. METHODS: Thirty-five patients after lung resection and 11 pneumothorax
      patients without surgery were treated with pleurodesis using 50 % glucose.
      Approximately, 200 mL of 50 % glucose solution was injected into the pleural
      space and repeated until the air leakage stopped. Cases in which the air leakage
      did not stop after three injections were considered to be unsuccessful and
      subsequently treated with conventional pleurodesis using OK-432. RESULTS: Thirty
      nine patients were successfully treated with 50 % glucose, although 7 patients
      required further treatment with OK-432. The unsuccessful group had some pulmonary
      comorbidities (P < 0.001), and the pleural effusion volume after pleurodesis was
      less than that in the successful group (P < 0.001). Although the air leakage did
      not stop in unsuccessful patients, the amount of air leakage markedly decreased.
      A temporary elevation of the blood sugar level was observed in 20 patients, but
      no other side effects had appeared. CONCLUSIONS: Pleurodesis with 50 % glucose is
      an easy, safe, and effective treatment modality. It is therefore considered to be
      a useful alternative method for pleurodesis.

PMID- 26206408
TI  - Prediction of Complications Following Partial Nephrectomy: Implications for
      Ablative Techniques Candidates.
AB  - BACKGROUND: Current guidelines recommend local tumour ablation (LTA) over partial
      nephrectomy (PN) in nonsurgical candidates; however, objective definitions of
      these candidates are lacking. OBJECTIVE: To identify specific patients who would
      benefit from LTA more than PN. DESIGN, SETTING, AND PARTICIPANTS: A population
      based assessment was performed of 2476 patients in the Surveillance Epidemiology
      and End Results-Medicare database who had cT1a kidney cancer treated with either
      LTA or PN, between 2000 and 2009. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      The outcome of the study was the relevant perioperative complications rate. A
      multivariable logistic regression model was fitted to predict the risk of
      complications after PN. Model-derived coefficients were used to calculate the
      risk of complication in case of PN among patients treated with LTA. Locally
      weighted scatterplot smoothing method was used to plot the observed complication
      rate against the predicted risk of complication in case of PN. RESULTS AND
      LIMITATIONS: At multivariable logistic regression, age (odds ratio [OR]: 1.04;
      p<0.001), Charlson comorbidity index (OR: 1.14; p<0.001), acute kidney injury
      (OR: 1.91; p=0.04), or chronic kidney disease (OR: 2.16; p=0.002), tumour size
      (OR: 1.02; p=0.01), and minimally invasive approach (OR: 0.77; p<0.03) emerged as
      significant predictors of complications. When LTA was chosen over PN, the
      reduction in the risk of complications was greatest in high-risk patients,
      intermediate in intermediate-risk patients, and least in low-risk patients.
      CONCLUSIONS: When postoperative complications are evaluated, the benefit of
      choosing LTA is not the same in all patients diagnosed with T1a kidney cancer.
      Specifically, patients at high risk of complications in case of PN may benefit
      the most from LTA and represent ideal LTA candidates. PATIENT SUMMARY: Elderly
      patients at high risk of complications in case of surgical treatment with partial
      nephrectomy for kidney cancer should be instructed that local tumour ablation
      might decrease their perioperative morbidity.

PMID- 26206409
TI  - The combined depletion of monoamines alters the effectiveness of subthalamic deep
      brain stimulation.
AB  - Non-motor symptoms of Parkinson's disease are under-studied and therefore not
      well treated. Here, we investigated the role of combined depletions of dopamine,
      norepinephrine and/or serotonin in the manifestation of motor and non-motor
      deficits in the rat. Then, we studied the impact of these depletions on the
      efficacy of deep brain stimulation of the subthalamic nucleus (STN-DBS). We
      performed selective depletions of dopamine, norepinephrine and serotonin, and the
      behavioral effects of different combined depletions were investigated using the
      open field, the elevated plus maze and the forced swim test. Bilateral dopamine
      depletion alone induced locomotor deficits associated with anxiety and mild
      "depressive-like" behaviors. Although additional depletions of norepinephrine
      and/or serotonin did not potentiate locomotor and anxiety disorders, combined
      depletions of the three monoamines dramatically exacerbated "depressive-like"
      behavior. STN-DBS markedly reversed locomotor deficits and anxiety behavior in
      animals with bilateral dopamine depletion alone. However, these improvements were
      reduced or lost by the additional depletion of norepinephrine and/or serotonin,
      indicating that the depletion of these monoamines may interfere with the
      antiparkinsonian efficacy of STN-DBS. Furthermore, our results showed that acute
      STN-DBS improved "depressive-like" disorder in animals with bilateral depletion
      of dopamine and also in animals with combined depletions of the three monoamines,
      which induced severe immobility in the forced swim test. Our data highlight the
      key role of monoamine depletions in the pathophysiology of anxiety and depressive
      like disorders and provide the first evidence of their negative consequences on
      the efficacy of STN-DBS upon the motor and anxiety disorders in the context of
      Parkinson's disease. 

PMID- 26206410
TI  - Severe hidradenitis suppurativa complicated by renal AA amyloidosis.
AB  - Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease
      affecting the skin folds. Multiple therapeutic options have been proposed for
      severe cases, but persistent responses are rarely seen. Important complications
      of HS are uncommon, and usually seen only in severe and unresponsive disease.
      Amyloid A (AA) amyloidosis is secondary to inflammatory chronic diseases, and is
      an uncommon complication of dermatological diseases. Only a few cases related
      with HS have been reported. We report the case of a 37-year-old patient who
      developed AA amyloidosis secondary to severe HS. 

PMID- 26206411
TI  - Neuropsychological functioning related to specific characteristics of nocturnal
      enuresis.
AB  - INTRODUCTION/BACKGROUND: There is a high comorbidity demonstrated in the
      literature between nocturnal enuresis and several neuropsychological
      dysfunctions, with special emphasis on attention deficit hyperactivity disorder
      (ADHD). However, the majority of the psychological studies did not include full
      non-invasive screening and failed to differentiate between monosymptomatic
      nocturnal enuresis (MNE) and non-MNE patients. OBJECTIVE: The present study
      primarily aimed to investigate the association between nocturnal enuresis and
      (neuro)psychological functioning in a selective homogeneous patient group,
      namely: children with MNE and associated nocturnal polyuria (NP). Secondly, the
      study investigated the association between specific characteristics of nocturnal
      enuresis (maximum voided volume, number of wet nights and number of nights with
      NP) and ADHD-inattentive symptoms, executive functioning and quality of life.
      STUDY DESIGN: The psychological measurements were multi-informant (parents,
      children and teachers) and multi-method (questionnaires, clinical interviews and
      neuropsychological testing). RESULTS: Thirty children aged 6-16 years (mean 10.43
      years, SD 3.08) were included. Of them, 80% had at least one psychological, motor
      or neurological difficulty. The comorbid diagnosis of ADHD, especially the
      predominantly inattentive presentation, was most common. According to the
      teachers, a low maximum voided volume (corrected for age) was associated with
      more attention problems, and a high number of nights with NP was associated with
      more behaviour-regulation problems. No significant correlations were found
      between specific characteristics of enuresis and quality of life. Details are
      demonstrated in Table. DISCUSSION: The children were recruited from a tertiary
      referral centre, which resulted in selection bias. Moreover, NP was defined as a
      urine output exceeding 100% of the expected bladder capacity for age (EBC), and
      not according to the expert-opinion-based International Children's Continence
      Society norm of 130% of EBC. The definition for NP of a urine output exceeding
      100% of the EBC is more in line with the recent findings of the Aarhus group.
      CONCLUSIONS: For children with MNE and associated NP, a high comorbidity with the
      predominantly inattentive presentation of ADHD was demonstrated. Children
      experienced problems with daytime functioning in relation to their wetting
      problem at night. According to the teachers, a low maximum voided volume was
      associated with more attention problems, and a high number of nights with NP was
      associated with more behaviour-regulation problems. Although comorbidity is still
      the appropriate word to use, the observation favours a more complex pathogenesis
      of enuresis with a common pathway in the central nervous system, including:
      neurotransmitters, influencing neuropsychological functioning as well as sleep,
      circadian rhythm of diuresis and bladder function control.

PMID- 26206412
TI  - Oral health-related quality-of-life among children in Swedish dental care: The
      impact from malocclusions or orthodontic treatment need.
AB  - OBJECTIVES: To describe oral health-related quality-of-life (OHRQoL) and the
      impact of malocclusions or orthodontic treatment need in a cohort of children in
      Swedish dental care, using the Swedish version of the Child Perceptions
      Questionnaire-Impact Short Form (CPQ11-14-ISF:16). SUBJECTS AND METHODS: Two
      hundred and fifty-seven children (mean age = 11.5 years, SD = 0.8, range = 9.8
      13.5 years) completed the CPQ11-14-ISF:16 in conjunction with a clinical
      examination. In addition to malocclusions and orthodontic treatment need (based
      on the Index of Orthodontic Treatment Need-Dental Health Component), possible
      confounders (caries, enamel defects, dental trauma, headache and socio-economic
      markers) were recorded. Children also rated their own dental fear on the
      Children's Fear Survey Schedule-Dental Sub-scale (CFSS-DS). RESULTS: The mean
      total CPQ11-14-ISF:16 score was 9.31. The logistic regression analyses revealed
      an impact of orthodontic treatment need on OHRQoL (CPQ), but no clear association
      between higher severity and higher impact on OHRQoL was seen. Dental fear and
      headache appeared to discriminate for poorer OHRQoL. No impact from caries,
      enamel defects, dental trauma, or socio-economic markers was revealed.
      CONCLUSIONS: This cohort of children reported good self-perceived OHRQoL. Effects
      on OHRQoL from malocclusions or orthodontic treatment need were limited and
      inconsistent. Dental fear and headache were found to be more distinct impact
      factors on OHRQoL than were malocclusions or orthodontic treatment need.

PMID- 26206413
TI  - Cutaneous tissue expressions of matrix metalloproteinase 2 and tissue inhibitor
      of metalloproteinase 2 are associated with a high degree of disability at
      diagnosis of hanseniasis.

PMID- 26206414
TI  - Electrospinning deposition of hydrogel fibers used as scaffold for biomembranes.
      Thermal stability of DPPC corroborated by ellipsometry.
AB  - DPPC bilayers were deposited over thin hydrogel scaffolds using the Langmuir
      Blodgett technique (with DPPC thickness ~ 6.2 nm). Wrinkled hydrogels films were
      used to maintain a moist environment in order to enhance DPPC bilayer stability.
      Polymer mixtures were prepared using HEMA (as a base monomer) and DEGDMA,
      PEGDA575, PEGDA700 or AAm (as crosslinking agents); a thermal initiator was added
      to obtain a final pre-hydrogel (oligomer) with an adequate viscosity for thin
      film formation. This mixture was deposited as wrinkled film/fibers over
      hydrophilic silicon wafers using an electrospinning technique. Later, these
      samples were exposed to UV light to trigger photopolymerization, generating
      crosslinking bonds between hydrogel chains; this process also generated remnant
      surface stresses in the films that favored wrinkle formation. In the cases where
      DEGDMA and AAm were used as crosslinking agents, HEMA was added in higher
      amounts. The resultant polymer film surface showed homogenous layering with some
      small isolated clusters. If PEGDA575/700 was used as the crosslinking agent, we
      observed the formation of polymer wrinkled thin films, composed by main and
      secondary chains (with different dimensions). Moreover, water absorption and
      release was found to be mediated through surface morphology, ordering and film
      thickness. The thermal behavior of biomembranes was examined using ellipsometry
      techniques under controlled heating cycles, allowing phases and phase transitions
      to be detected through slight thickness variations with respect to temperature.
      Atomic force microscopy was used to determinate surface roughness changes
      according to temperature variation, temperature was varied sufficiently for the
      detection and recording of DPPC phase limits. Contact angle measurements
      corroborated and quantified system wettability, supporting the theory that
      wrinkled hydrogel films act to enhance DPPC bilayer stability during thermal
      cycles.

PMID- 26206415
TI  - Image-guided elbow interventions: a literature review of interventional treatment
      options.
AB  - Over the years, a wide range of image-guided interventional therapies have been
      used in treating different elbow pathologies, many of which are predominantly
      based on anecdotal and low-level study findings. This article critically assesses
      the existing literature and discusses the efficacy of the most commonly utilized
      interventional procedures for elbow pathology. 

PMID- 26206416
TI  - Chromium deposition and poisoning of La(0.8)Sr(0.2)MnO3 oxygen electrodes of
      solid oxide electrolysis cells.
AB  - The effect of the presence of an Fe-Cr alloy metallic interconnect on the
      performance and stability of La(0.8)Sr(0.2)MnO3 (LSM) oxygen electrodes is
      studied for the first time under solid oxide electrolysis cell (SOEC) operating
      conditions at 800  degrees C. The presence of the Fe-Cr interconnect accelerates
      the degradation and delamination processes of the LSM oxygen electrodes. The
      disintegration of LSM particles and the formation of nanoparticles at the
      electrode/electrolyte interface are much faster as compared to that in the
      absence of the interconnect. Cr deposition occurs in the bulk of the LSM oxygen
      electrode with a high intensity on the YSZ electrolyte surface and on the LSM
      electrode inner surface close to the electrode/electrolyte interface. SIMS, GI
      XRD, EDS and XPS analyses clearly identify the deposition and formation of
      chromium oxides and strontium chromate on both the electrolyte surface and
      electrode inner surface. The anodic polarization promotes the surface segregation
      of SrO and depresses the generation of manganese species such as Mn(2+). This is
      evidently supported by the observation of the deposition of SrCrO4, rather than
      (Cr,Mn)3O4 spinels as in the case under the operating conditions of solid oxide
      fuel cells. The present results demonstrate that the Cr deposition is essentially
      a chemical process, initiated by the nucleation and grain growth reaction between
      the gaseous Cr species and segregated SrO on LSM oxygen electrodes under SOEC
      operating conditions.

PMID- 26206417
TI  - Quasiparticle self-consistent GW study of cuprates: electronic structure, model
      parameters, and the two-band theory for Tc.
AB  - Despite decades of progress, an understanding of unconventional superconductivity
      still remains elusive. An important open question is about the material
      dependence of the superconducting properties. Using the quasiparticle self
      consistent GW method, we re-examine the electronic structure of copper oxide high
      Tc materials. We show that QSGW captures several important features, distinctive
      from the conventional LDA results. The energy level splitting between d(x(2)
      y(2)) and d(3z(2)-r(2)) is significantly enlarged and the van Hove singularity
      point is lowered. The calculated results compare better than LDA with recent
      experimental results from resonant inelastic xray scattering and angle resolved
      photoemission experiments. This agreement with the experiments supports the
      previously suggested two-band theory for the material dependence of the
      superconducting transition temperature, Tc.

PMID- 26206418
TI  - Vector species richness increases haemorrhagic disease prevalence through
      functional diversity modulating the duration of seasonal transmission.
AB  - Although many parasites are transmitted between hosts by a suite of arthropod
      vectors, the impact of vector biodiversity on parasite transmission is poorly
      understood. Positive relationships between host infection prevalence and vector
      species richness (SR) may operate through multiple mechanisms, including (i)
      increased vector abundance, (ii) a sampling effect in which species of high
      vectorial capacity are more likely to occur in species-rich communities, and
      (iii) functional diversity whereby communities comprised species with distinct
      phenologies may extend the duration of seasonal transmission. Teasing such
      mechanisms apart is impeded by a lack of appropriate data, yet could highlight a
      neglected role for functional diversity in parasite transmission. We used
      statistical modelling of extensive host, vector and microparasite data to test
      the hypothesis that functional diversity leading to longer seasonal transmission
      explained variable levels of disease in a wildlife population. We additionally
      developed a simple transmission model to guide our expectation of how an
      increased transmission season translates to infection prevalence. Our study
      demonstrates that vector SR is associated with increased levels of disease
      reporting, but not via increases in vector abundance or via a sampling effect.
      Rather, the relationship operates by extending the length of seasonal
      transmission, in line with theoretical predictions.

PMID- 26206419
TI  - Potential Roles of Mhealth for Community Health Workers: Formative Research With
      End Users in Uganda and Mozambique.
AB  - BACKGROUND: Community health workers are reemerging as an essential component of
      health systems in low-income countries. However, there are concerns that unless
      they are adequately supported, their motivation and performance will be
      suboptimal. mHealth presents an opportunity to improve support for community
      health workers; however, most interventions to date have been designed through a
      top-down approach, rarely involve the end user, and have not focused on
      motivation. OBJECTIVE: To use formative research to explore the views of
      community health workers in Uganda and Mozambique on the potential role of
      mHealth in their work delivering integrated community case management of
      children. METHODS: We conducted 24 in-depth interviews and 5 focus group
      discussions with community health workers in Uganda and Mozambique. Data were
      collected on: current phone use, preferred phone and charger characteristics, and
      perceptions of a range of potential mHealth interventions. Interviews were
      conducted in the local language, were audio recorded and converted into expanded
      notes. Interviews were coded for key thematic areas using both deductive and
      inductive codes. Deductive codes included mHealth's potential impact on
      motivation and performance. RESULTS: The most salient roles of mHealth in
      improving performance and motivation were reducing the need for travel, improving
      efficiency and planning, receiving feedback and information, and improving
      communication with supervisors and other community health workers. This was
      mostly through improved voice and short message service (SMS) text communication.
      Specific components of mHealth interventions that participants felt could improve
      motivation included increasing their visibility and credibility through branding
      of phones; providing an SMS response to data submission; and sending SMS messages
      about the importance of their work and achievements, rather than just reminders
      or technical messages. Participants identified feasibility issues related to the
      language of SMS messages, network coverage, and the need for a balance between
      phone function and battery life. Phones with a dual SIM cards would ameliorate
      network problems but would reduce battery life. The provision of a solar charger
      was viewed as beneficial. CONCLUSIONS: Conducting formative research with end
      users is likely to improve mHealth interventions by: (1) identifying
      interventions that are likely to have the greatest impact and be the most
      acceptable, (2) developing salient SMS messages, and (3) identifying feasibility
      issues. mHealth interventions also could have an important impact on health
      worker motivation, which should be considered by intervention developers and in
      evaluations, especially as small modifications could have a significant impact.
      Our study suggests that using phones to improve direct communication should be
      considered, even when planners aim to focus on the provision of a specific
      application.

PMID- 26206420
TI  - An overview of early investigational therapies for chemoresistant ovarian cancer.
AB  - INTRODUCTION: Epithelial ovarian cancer (EOC) is the fourth commonest cause of
      female cancer death in the developed world. Although progress in treatment has
      improved survival, ~ 80% of patients with advanced EOC will experience a
      recurrence and eventually will become resistant to chemotherapy. The aim of
      treatment for chemoresistant EOC has traditionally been limited to palliation of
      symptoms but the recent introduction of new therapies targeting molecular
      pathways is beginning to demonstrate improvements in disease control. AREAS
      COVERED: This review provides an overview of early investigational drugs for the
      treatment of 'platinum-resistant' EOC. The article is based on English peer
      reviewed articles located on MEDLINE and related abstracts presented at major
      international meetings. EXPERT OPINION: Drugs targeting several pathways are
      increasingly used to treat 'platinum-resistant' EOC. Currently, drugs targeting
      the angiogenesis pathway have been shown to significantly improve patient
      outcome. Studies are also being undertaken with inhibitors of poly(ADP-ribose)
      polymerase (PARP), targeting the DNA repair pathway as it is possible that the
      benefits seen with these agents in 'platinum-sensitive' disease will apply to
      those with 'platinum-resistant' disease. The discovery of predictive biomarkers
      that identify patients which benefit from these targeted therapies is paramount
      to the success of these treatments in the future.

PMID- 26206421
TI  - Fetal hematopoietic stem cells express MFG-E8 during mouse embryogenesis.
AB  - The milk fat globule-EGF-factor 8 protein (MFG-E8) has been identified in various
      tissues, where it has an important role in intercellular interactions, cellular
      migration, and neovascularization. Previous studies showed that MFG-E8 is
      expressed in different cell types under normal and pathophysiological conditions,
      but its expression in hematopoietic stem cells (HSCs) during hematopoiesis has
      not been reported. In the present study, we investigated MFG-E8 expression in
      multiple hematopoietic tissues at different stages of mouse embryogenesis. Using
      immunohistochemistry, we showed that MFG-E8 was specifically expressed in CD34(+)
      HSCs at all hematopoietic sites, including the yolk sac, aorta-gonad-mesonephros
      region, placenta and fetal liver, during embryogenesis. Fluorescence-activated
      cell sorting and polymerase chain reaction analyses demonstrated that CD34(+)
      cells, purified from the fetal liver, expressed additional HSC markers, c-Kit and
      Sca-1, and that these CD34(+) cells, but not CD34(-) cells, highly expressed MFG
      E8. We also found that MFG-E8 was not expressed in HSCs in adult mouse bone
      marrow, and that its expression was confined to F4/80(+) macrophages. Together,
      this study demonstrates, for the first time, that MFG-8 is expressed in fetal HSC
      populations, and that MFG-E8 may have a role in embryonic hematopoiesis. 

PMID- 26206422
TI  - Hepatitis C virus genotype and subtype distribution in Chinese chronic hepatitis
      C patients: nationwide spread of HCV genotypes 3 and 6.
AB  - BACKGROUND: Hepatitis C virus (HCV) genotype and subtype are related to disease
      progression and response to antiviral therapy. Current HCV genotype and subtype
      distribution data, especially for genotypes 3 and 6, are limited in China. Our
      purpose was to investigate the current HCV genotype and subtype distributions in
      chronic hepatitis C patients in China. METHODS: Chronic hepatitis C patients (n =
      1012) were enrolled, and demographic information and possible transmission risk
      factors were collected. Serum samples were subjected to reverse-transcription
      polymerase chain reaction, followed by direct DNA sequencing and phylogenetic
      analysis of the NS5B and core/E1 regions to determine HCV genotypes/subtypes. The
      geographical distributions of HCV genotypes/subtypes were analyzed. Demographic
      information and transmission risk factors were compared between different HCV
      genotypes/subtypes. RESULTS: Four genotypes and seven subtypes of HCV were
      detected in 970 patients. Subtypes 1b, 2a, 3a, 6a, 3b, 6n, and 1a were detected
      at frequencies of 71.96%, 19.90%, 3.20%, 2.16%, 1.96%, 0.41%, and 0.41%,
      respectively. Genotypes 3 and 6 showed an increasingly wide geographic
      distribution over time. Patients with subtypes 1b and 2a were older than those
      with 3a, 3b, 6a, and 6n subtypes (p < 0.05 in all subtypes). More genotype 1 and
      2 patients underwent blood transfusion than those with genotype 3 (all p < 0.05).
      More genotype 3 and 6 patients had a history of intravenous drug use than those
      with genotypes 1 and 2 (all p < 0.05). CONCLUSIONS: Though subtypes 1b and 2a are
      still the most prevalent HCV subtypes in China, genotype 3 and 6 HCV infections
      have already spread nationwide from southern and western China.

PMID- 26206424
TI  - Effects of androgen on immunohistochemical localization of androgen receptor and
      Connexin 43 in mouse ovary.
AB  - Androgens have essential roles in the regulation of follicular development and
      female fertility. Androgen excess is the leading defect in polycystic ovary
      syndrome (PCOS) patients and involved in the ovarian dysfunction. The aim of this
      study was to elucidate the regarding regulatory role of androgen in the
      follicular development of female mouse. Immunohistochemical staining and Western
      blot analyses were performed to detect androgen receptor (AR) and Connexin 43
      (Cx43) expression in ovaries from both control and testosterone-treated group
      mice. In this study, localizations of AR and Cx43 were dramatically altered in
      testosterone-treated mouse ovaries. In addition, AR expression was significantly
      increased, whereas Cx43 expression was markedly decreased after testosterone
      treatment. Alterations of AR and Cx43 expression by testosterone with concomitant
      reduction of MII oocytes. Overall, these results suggest the involvement of
      androgen in the regulation of AR and Cx43 localizations in mouse ovary.
      Alterations of AR and Cx43 expression by testosterone may affect normal
      folliculogenesis. Together these findings will enable us to begin understanding
      the important roles of AR and Cx43 actions in the regulation of follicular
      development, as well as providing insights into the role of AR and Cx43 actions
      in the androgen-associated reproductive diseases such as PCOS.

PMID- 26206423
TI  - The Minnesota Green Tea Trial (MGTT), a randomized controlled trial of the
      efficacy of green tea extract on biomarkers of breast cancer risk: study
      rationale, design, methods, and participant characteristics.
AB  - PURPOSE: The Minnesota Green Tea Trial (MGTT) was a randomized, placebo
      controlled, double-blinded trial investigating the effect of daily green tea
      extract consumption for 12 months on biomarkers of breast cancer risk. METHODS:
      Participants were healthy postmenopausal women at high risk of breast cancer due
      to dense breast tissue with differing catechol-O-methyltransferase (COMT)
      genotypes. The intervention was a green tea catechin extract containing 843.0 +/-
      44.0 mg/day epigallocatechin gallate or placebo capsules for 1 year. Annual
      digital screening mammograms were obtained at baseline and month 12, and fasting
      blood and 24-h urine samples were provided at baseline and at months 6 and 12.
      Primary endpoints included changes in percent mammographic density, circulating
      endogenous sex hormones, and insulin-like growth factor axis proteins; secondary
      endpoints were changes in urinary estrogens and estrogen metabolites and
      circulating F2-isoprostanes, a biomarker of oxidative stress. RESULTS: The MGTT
      screened more than 100,000 mammograms and randomized 1,075 participants based on
      treatment (green tea extract vs. placebo), stratified by COMT genotype activity
      (high COMT vs. low/intermediate COMT genotype activity). A total of 937 women
      successfully completed the study and 138 dropped out (overall dropout rate = 12.8
      %). CONCLUSIONS: In this paper we report the rationale, design, recruitment,
      participant characteristics, and methods for biomarker and statistical analyses.

PMID- 26206425
TI  - Can we predict efficacy of the ketogenic diet in children with refractory
      epilepsy?
AB  - BACKGROUND: The ketogenic diet (KD) can be effective in reducing seizures in
      children. Predictors of success have not been identified yet. AIMS: To evaluate
      efficacy of KD treatment and to search for child- or diet-related factors that
      can predict its efficacy at 12 months follow-up. In addition we wish to determine
      the usefulness of a 3-month KD trial period. METHODS: Single center retrospective
      study in a university paediatric hospital of children with refractory epilepsy in
      which the KD had been initiated. Patient and diet characteristics as well as
      seizure reduction data were obtained from medical records and parental review.
      Efficacy of the KD was defined as >= 50% seizure reduction. Variables were
      evaluated in their relation to a successful treatment at three and 12 months
      after diet initiation. RESULTS: During a 9.5-year period, the KD was initiated in
      59 children with refractory epilepsy. Twenty-four children were still on the KD
      after 12 months, and 21 experienced >=50% seizure reduction. Success of the KD at
      three months was significantly related to a successful response to KD treatment
      at 12 months (p < 0.001). CONCLUSIONS: The KD can be an effective treatment in
      reducing seizures in children with refractory epilepsy. No significant
      relationships between variables and efficacy at 12 months were revealed. Children
      with a successful response at 3 months were significantly more likely to achieve
      success at 12 months of KD treatment.

PMID- 26206426
TI  - Cellular and Molecular Mechanisms of Phenotypic Switch in Gastrointestinal Smooth
      Muscle.
AB  - As a general rule, smooth muscle cells (SMC) are able to switch from a
      contractile phenotype to a less mature synthetic phenotype. This switch is
      accompanied by a loss of differentiation with decreased expression of contractile
      markers, increased proliferation as well as the synthesis and the release of
      several signaling molecules such as pro-inflammatory cytokines, chemotaxis
      associated molecules, and growth factors. This SMC phenotypic plasticity has
      extensively been investigated in vascular diseases, but interest is also emerging
      in the field of gastroenterology. It has in fact been postulated that altered
      microenvironmental conditions, including the composition of microbiota, could
      trigger the remodeling of the enteric SMC, with phenotype changes and consequent
      alterations of contraction and impairment of gut motility. Several molecular
      actors participate in this phenotype remodeling. These include extracellular
      molecules such as cytokines and extracellular matrix proteins, as well as
      intracellular proteins, for example, transcription factors. Epigenetic control
      mechanisms and miRNA have also been suggested to participate. In this review key
      roles and actors of smooth muscle phenotypic switch, mainly in GI tissue, are
      described and discussed in the light of literature data available so far. J.
      Cell. Physiol. 231: 295-302, 2016. (c) 2015 Wiley Periodicals, Inc. 

PMID- 26206427
TI  - Novel 9-Alkyl- and 9-Alkylidene-Substituted 1alpha,25-Dihydroxyvitamin D3
      Analogues: Synthesis and Biological Examinations.
AB  - Continuing the structure-activity relationship studies in the vitamin D area, we
      designed and synthesized novel C-9 substituted calcitriol analogues, possessing
      different nonpolar groups at this position. 9alpha-Methyl-1alpha,25-(OH)2D3, both
      epimers of 9-methylene-10,19-dihydro-1alpha,25-(OH)2D3 as well as the parent
      vitamin with the "reversed" triene system, 9-methylene-19-nor-1alpha,25-(OH)2D3,
      were obtained from the previtamin D precursors, constructed by either Suzuki
      Miyaura, Sonogashira, or Stille couplings of the corresponding A- and C,D-ring
      fragments. An alternative synthetic path, leading to the latter vitamin and its
      homologue with 9-ethylidene group, involved formation of dienynes as precursors
      of the respective 19-norprevitamin D compounds. 9beta-Methyl-19-nor-1alpha,25
      (OH)2D3 was prepared by homogeneous hydrogenation with Wilkinson catalyst, and
      this analogue was found to be the most active in vitro. Moreover, 9alpha-methyl
      1alpha,25-(OH)2D3 and 9-methylene-19-nor-1alpha,25-(OH)2D3 showed some in vitro
      activity, however, the in vivo assays indicated only weak calcemic potency of
      these compounds in the intestinal calcium transport. 

PMID- 26206428
TI  - Review article: systematic review of three key strategies designed to improve
      patient flow through the emergency department.
AB  - To explore the literature regarding three key strategies designed to promote
      patient throughput in the ED. CINAHL, Medline, PubMed, Scopus and Australian
      Government databases were searched for articles published between 1980 and 2014
      using the key search terms ED flow/throughput, ED congestion, crowding,
      overcrowding, models of care, physician-assisted triage, medical assessment
      units, nurse practitioner, did not wait (DNW) and ED length of stay (LOS).
      Abstracts and articles not published in English and articles published before
      1980 were excluded from the review. Quantitative and qualitative studies were
      considered for inclusion. The National Health Medical Research Council (NHMRC)
      Level of Evidence Hierarchy (2009) was applied to included studies. Twenty-one
      articles met criteria for review. The level of evidence assessed using the NHMRC
      guidelines of studies ranged from I to IV, with the majority falling into the
      Level II-2 (n = 6) and III-3 (n = 9) range. ED LOS was the outcome most often
      reported. Study quality was limited with few studies adjusting for confounding
      factors. Only one level I systematic review was included in this review. Advanced
      practice nursing roles, physician-assisted triage and medical assessment units
      are models of care that can positively impact ED throughput. They have been shown
      to decrease ED LOS and DNW rates. Confounding factors, such as site specific
      staffing requirements, patient acuity and rest-of-hospital processes, can also
      impact on patient throughput through the ED. 

PMID- 26206429
TI  - Intestinal adaptation in short bowel syndrome: A case report.
AB  - Short bowel syndrome is a clinical entity that includes loss of energy, fluid,
      electrolytes or micronutrient balance because of inadequate functional intestinal
      length. This case report demonstrates the case of a woman who compensated for
      short bowel syndrome through intestinal adaptation, which is a complex process
      worthy of further investigation for the avoidance of dependence on total
      parenteral nutrition and of intestinal transplantation in such patients. 

PMID- 26206430
TI  - Endoscopic treatment of an oesophageal rupture using an over-the-scope clip
      (OTSC): A case report.
AB  - Oesophageal rupture (Boerhaave syndrome) is a rare but serious complication after
      vomiting. Early intervention is mandatory in order to avoid a deleterious outcome
      for the patient. This case report describes the endoscopic approach using an over
      the-scope clip. 

PMID- 26206431
TI  - Isolated enteric aspergillosis in a non severely immunocompromised patient. Case
      report and literature review.
AB  - Invasive aspergillosis is a life-threatening, opportunistic fungal infection that
      mainly affects immunocompromised patients, particularly those receiving
      immunosuppressive therapy or high-dose corticosteroids. The most common portal of
      entry in aspergillosis is the lung, so the isolated occurrence of intestinal
      aspergillosis in the absence of pulmonary disease is an unusual pattern. CASE
      REPORT: We report a case of a lung cancer patient who did not receive
      chemotherapy, presenting to the emergency department with fever and chills. The
      patient also developed abdominal pain and bloody diarrhoea during his
      hospitalisation. Colonoscopy revealed diffuse epithelial and subepithelial oedema
      of the terminal ileum, linear ulcers, denudation of the mucosa, and necrosis.
      Histopathological examination of terminal ileum diffuse biopsies showed
      haemorrhagic infiltrations, while microscopy revealed Y-shaped, branching septate
      hyphae, diagnostic for Aspergillus fungi. Additionally, the culture of biopsy
      samples showed the growth of Aspergillus fumigatus. The patient was negative for
      Aspergillus antibodies in his blood, and bronchoscopy and sputum samples were
      negative as well. CONCLUSION: This is a rare case of isolated aspergillosis of
      the small intestine, as there is no pulmonary or other systemic participation, as
      it also happens in a patient not being in a severely immunocompromised state.

PMID- 26206433
TI  - Insuring Young Adults in the United States Through the Affordable Care Act.

PMID- 26206432
TI  - Falls by individuals with chronic obstructive pulmonary disease: a preliminary 12
      month prospective cohort study.
AB  - BACKGROUND AND OBJECTIVE: Despite evidence of an increased fall risk in people
      with chronic obstructive pulmonary disease (COPD), there is a paucity of
      prospective fall data in this population. This preliminary study aimed to
      prospectively examine the prevalence rate, incidence rate and associated risk
      factors for falls in a sample of community-dwelling people with COPD over 1 year.
      METHODS: Forty-one participants with stable COPD (mean +/- SD) aged 71 +/- 8
      years with a forced expiratory volume in 1 s of 45.1 +/- 16.2% predicted were
      included. At baseline, participants' demographic, physical function and fall
      related measures were documented. Falls were monitored for 12 months following
      initial assessments. RESULTS: The prevalence of people having falls was 40% (95%
      CI: 24-56%); amongst these, 75% had frequent falls. The overall fall incidence
      rate was 1.17 falls/person-year. Risk factors associated with a higher fall
      incidence rate ratio (IRR) in COPD were: number of pack-years (IRR: 1.02; 95%CI:
      1.00,1.04), comorbidities (IRR: 2.02; 95%CI: 1.42,3.06), number of medications
      (IRR: 1.15; 95%CI: 1.00,1.34), history of falls in the previous year (IRR: 1.89;
      95%CI: 1.10,3.34), fear of falling (IRR: 1.08; 95% CI: 1.02,1.14) and higher
      score in a fall risk assessment questionnaire for older adults (IRR: 1.14; 95%
      CI: 1.05,1.25); P <= 0.05. When adjusted for age, only pack-years (P = 0.01),
      number of comorbidities (P < 0.001) and history of falls (P = 0.03) were related
      to an increased fall incidence. CONCLUSIONS: These preliminary findings
      demonstrated the fall prevalence and incidence rate in community-dwelling people
      with stable COPD and identified prospective risk factors for an increased fall
      incidence, which suggest potential mitigation strategies.

PMID- 26206434
TI  - With Transgender Health Inequities so Large and the Need so Great, the Burden Is
      on All of Us to Find Solutions.

PMID- 26206435
TI  - Promoting Quality Intimate Partner Relationships Among Adults With a History of
      Child Maltreatment.

PMID- 26206436
TI  - Facebook Use and Disordered Eating in College-Aged Women.
AB  - PURPOSE: Disordered eating behavior-dieting, laxative use, fasting, binge eating
      is common in college-aged women (11%-20%). A documented increase in the number of
      young women experiencing eating psychopathology has been blamed on the rise of
      engagement with social media sites such as Facebook. We predicted that college
      aged women's Facebook intensity (e.g., the amount of time spent on Facebook,
      number of Facebook friends, and integration of Facebook into daily life), online
      physical appearance comparison (i.e., comparing one's appearance to others' on
      social media), and online "fat talk" (i.e., talking negatively about one's body)
      would be positively associated with their disordered eating behavior. METHODS: In
      an online survey, 128 college-aged women (81.3% Caucasian, 6.7% Asian, 9.0%
      African-American, and 3.0% Other) completed items, which measured their
      disordered eating, Facebook intensity, online physical appearance comparison,
      online fat talk, body mass index, depression, anxiety, perfectionism,
      impulsivity, and self-efficacy. RESULTS: In regression analyses, Facebook
      intensity, online physical appearance comparison, and online fat talk were
      significantly and uniquely associated with disordered eating and explained a
      large percentage of the variance in disordered eating (60%) in conjunction with
      covariates. However, greater Facebook intensity was associated with decreased
      disordered eating behavior, whereas both online physical appearance comparison
      and online fat talk were associated with greater disordered eating. CONCLUSIONS:
      College-aged women who endorsed greater Facebook intensity were less likely to
      struggle with disordered eating when online physical appearance comparison was
      accounted for statistically. Facebook intensity may carry both risks and benefits
      for disordered eating.

PMID- 26206437
TI  - More Than Poverty: The Effect of Child Abuse and Neglect on Teen Pregnancy Risk.
AB  - PURPOSE: The purpose of the study was to compare risk for teen pregnancies
      between children living in poverty with no child protective services (CPS) report
      history and those in poverty with a history of CPS report. METHODS: Children
      selected from families in poverty, both with and without CPS report histories
      were prospectively followed from 1993 to 2009 using electronic administrative
      records from agencies including CPS, emergency departments, Medicaid services,
      and juvenile courts. A total of 3,281 adolescent females were followed until the
      age of 18 years. RESULTS: For teens with history of poverty only, 16.8% had been
      pregnant at least once by the age of 17 years. In teens with history of both
      poverty and report of child abuse or neglect, 28.9% had been pregnant at least
      once by the age of 17 years. Although multivariate survival analyses revealed
      several other significant factors at the family and youth services levels, a
      report of maltreatment remained significant (about a 66% higher risk).
      CONCLUSIONS: Maltreatment is a significant risk factor for teen pregnancy among
      low income youth even after controlling for neighborhood disadvantage, other
      caregiver risks and indicators of individual emotional and behavioral problems.

PMID- 26206438
TI  - Quality of Parent-Adolescent Conversations About Sex and Adolescent Sexual
      Behavior: An Observational Study.
AB  - PURPOSE: Studies suggest that the quality of parent-adolescent communication
      about sex uniquely predicts adolescent sexual behavior. Previous studies have
      relied predominantly on self-report data. Observational methods, which are not
      susceptible to self-report biases, may be useful in examining the associations
      between the quality of parent-adolescent communication about sex and adolescent
      sexual behavior more objectively. METHODS: With a sample of adolescents (N = 55,
      58% male, 44% white, Mage = 15.8) and their parents, we used hierarchical
      logistic regression analyses to examine the associations between the observed
      quality of parent-adolescent communication about dating and sex and the
      likelihood of adolescents' sexual intercourse. RESULTS: The quality of parent
      adolescent communication about dating and sex predicted sexual behavior.
      Specifically, lecturing was associated with a higher likelihood of adolescents
      having had sexual intercourse. CONCLUSIONS: The quality of parent-adolescent
      communication about sex is a unique correlate of adolescent sexual behavior and
      warrants further investigation. Thus, it serves as a potential target of
      preventive interventions that aim to foster adolescent sexual health behaviors.

PMID- 26206439
TI  - Prospective Predictors of Novel Tobacco and Nicotine Product Use in Emerging
      Adulthood.
AB  - PURPOSE: The purpose of this study was to investigate whether risk factors for
      cigarette smoking assessed in adolescence predict the use of novel tobacco and
      nicotine products (hookah, little cigars, and e-cigarettes) in early emerging
      adulthood. METHODS: In a longitudinal study (N = 862), risk factors were measured
      in middle and high school, and novel product use was measured in emerging
      adulthood (mean age 22.4 years). Structural equation modeling was used to test a
      model predicting lifetime use of any of hookah, little cigars, and e-cigarettes
      in early emerging adulthood from distal predictors (gender, maternal smoking
      through Grade 8; already tried alcohol, cigarettes, or marijuana by Grade 8; and
      sensation seeking at Grade 8) and potential mediators (intentions to smoke
      cigarettes, drink alcohol or smoke marijuana at Grade 9, and smoking trajectory
      across high school). RESULTS: The most prevalent novel tobacco product was hookah
      (21.7%), followed by little cigars (16.8%) and e-cigarettes (6.6%). Maternal
      smoking, having already tried substances, and sensation seeking each predicted
      the use of at least one of these products via an indirect path through intentions
      to use substances and membership in a high-school smoking trajectory.
      CONCLUSIONS: Risk factors for cigarette smoking were found to predict novel
      tobacco use, suggesting that interventions to prevent cigarette smoking could be
      extended to include common novel tobacco products.

PMID- 26206440
TI  - Trends Among U.S. High School Seniors in Recent Marijuana Use and Associations
      With Other Substances: 1976-2013.
AB  - PURPOSE: The purpose of this study was to describe historical trends in rates of
      recent substance use and associations between marijuana and other substances,
      among U.S. high school seniors by race and gender. METHODS: Data from Monitoring
      the Future (1976-2013; N = 599,109) were used to estimate historical trends in
      alcohol use, heavy episodic drinking (HED), cigarette use, and marijuana use. We
      used time-varying effect models to flexibly estimate changes in associations of
      substance use behaviors. RESULTS: Past-month marijuana use rates peaked in the
      1970s, declined through 1990, then rose again to reach levels of use of more than
      20% for both black and white participants. Recent years show increasing
      disparities across groups such that males, and in particular black youth, are on
      a trajectory toward higher use. This rise in marijuana use is particularly
      concerning among black youth, with rates far exceeding those for cigarette use
      and HED. The association of marijuana use with both cigarette use and HED is
      particularly high in recent years among black adolescents. CONCLUSIONS: Substance
      use recently declined among high school seniors, except for marijuana use,
      particularly among black youth. The increasing association between marijuana and
      other substances among black adolescents suggests future amplification in
      critical health disparities.

PMID- 26206441
TI  - Predicting Young Adult Degree Attainment by Late Adolescent Marijuana Use.
AB  - PURPOSE: The purpose of this study was to assess whether infrequent and frequent
      marijuana use at age 19/20 years predicts receipt of educational degrees by the
      mid-20s, independent of confounding age 18 adolescent risk factors. METHODS: Data
      were from the Monitoring the Future study, an annual nationally representative
      survey of high school seniors followed into adulthood. Thirteen cohorts (1990
      2002) of high school seniors were followed longitudinally to their mid-20s (n =
      4,925; 54% female). We used logistic regression and propensity score matching
      with successive inclusion of age 18 risk factors and substance use to compare age
      19/20 frequent marijuana users (six or more occasions in past 30 days) to
      nonusers, frequent users to infrequent users (1-6 occasions), and infrequent
      users to nonusers on their likelihood of degree attainment by the mid-20s.
      RESULTS: Frequent marijuana users were less likely than infrequent users and
      nonusers to earn bachelor's degrees, even after controlling for a host of age 18
      risk factors (e.g., family socioeconomic background, academic performance,
      educational expectations, truancy). However, these differences were reduced in
      magnitude to statistical nonsignificance when we controlled for age 18 substance
      use. Across analyses, the proportion reaching this educational milestone did not
      differ significantly between infrequent users and nonusers. CONCLUSIONS: Results
      support a growing body of work suggesting that frequent marijuana use predicts a
      lower likelihood of postsecondary educational attainment, and this difference may
      originate during secondary school.

PMID- 26206442
TI  - Evaluation of Outcomes in Adolescent Inflammatory Bowel Disease Patients
      Following Transfer From Pediatric to Adult Health Care Services: Case for
      Transition.
AB  - PURPOSE: We aimed to evaluate the impact of a transition service on clinical and
      developmental outcomes in adolescent Inflammatory Bowel Disease (IBD) patients on
      transfer to adult health care services. METHODS: We reviewed the records of IBD
      patients diagnosed in pediatric care following their transfer/attendance to the
      adult IBD service. The data on patients who attended the transition service were
      compared with those who did not pass through the transition service. RESULTS:
      Seventy-two patients were included in the study 41M and 31F. Forty-four patients
      went through the transition system (Group A), and 28 had no formalized transition
      arrangement before transfer (Group B). A significantly higher number of Group B
      patients needed surgery within 2 years of transfer when compared with patients in
      Group A (46% vs. 25%, p = .01). Sixty-one percent of patients in Group B needed
      at least one admission within 2 years of transfer when compared with 29% of Group
      A patients (p = .002). Nonattendance at clinics was higher in Group B patients
      with 78% having at least one nonattendance, whereas 29% of Group A failed to
      attend at least one appointment (p = .001). In addition, drug compliance rates
      were higher in the transition group when compared with Group B (89% and 46%,
      respectively; p = .002). A higher proportion of transitioned patients achieved
      their estimated maximum growth potential when completing adolescence. There was a
      trend toward higher dependence on opiates and smoking in Group B patients.
      CONCLUSIONS: In adolescent IBD patients, transition care is associated with
      better disease specific and developmental outcomes. Prospective studies of
      different models of transition care in IBD are needed.

PMID- 26206443
TI  - Borderline and Long QT Syndrome in Adolescent Athletes Taking Medications.
AB  - PURPOSE: Adolescent athletes undergo preparticipation screening for long QT
      syndrome. Medications that are associated with QT interval prolongation are
      increasingly being prescribed to precollege students. The side effect profile of
      these medications during exercise is unknown. The aims of this study were to (1)
      measure the prevalence of medications known to be associated with QT interval
      prolongation taken by adolescents participating in athletics and (2) to determine
      the association between the use of these medications and QT interval prolongation
      in adolescents participating in athletics. METHODS: Sports preparticipation exams
      were performed on 484 students at an urban high school. This consisted of a
      physical examination, 12-Lead electrocardiogram, and health history including
      current prescription and over-the-counter medications. Electrocardiograms were
      interpreted by a pediatric cardiologist using Bazett's correction formula.
      Descriptive statistics were used to characterize the cohort. The participants'
      parents consented to the preparticipation examination before history and
      physicals. RESULTS: No athletes exhibited a corrected QT interval >500 ms.
      Borderline long QT was identified in 6.65% of the subjects. In this study, 7.64%
      of the subjects reported that they were taking medications associated with QT
      prolongation. After controlling for age and gender, medication usage was not
      significantly related to the presence a borderline long QT interval. CONCLUSIONS:
      Although adolescent athletes are taking medications associated with QT interval
      prolongation, their side effect profile during exercise is unknown. Although
      there was no significant association between medications and borderline long QT,
      these data were taken from adolescent athletes at rest. The prevalence of
      adolescents participating in athletics and taking medications associated with QT
      interval prolongation was significant. There appears to be a very low risk of QT
      prolongation >500 ms at rest in this cohort.

PMID- 26206444
TI  - Perceived and Police-Reported Neighborhood Crime: Linkages to Adolescent Activity
      Behaviors and Weight Status.
AB  - PURPOSE: Inadequate physical activity and obesity during adolescence are areas of
      public health concern. Questions exist about the role of neighborhoods in the
      etiology of these problems. This research addressed the relationships of
      perceived and objective reports of neighborhood crime to adolescent physical
      activity, screen media use, and body mass index (BMI). METHODS: Socioeconomically
      and racially/ethnically diverse adolescents (N = 2,455, 53.4% female) from 20
      urban, public middle and high schools in Minneapolis/St. Paul, Minnesota
      responded to a classroom survey in the Eating and Activity in Teens 2010 study.
      BMI was measured by research staff. Participants' mean age was 14.6 (standard
      deviation = 2.0); 82.7% represented racial/ethnic groups other than non-Hispanic
      white. Linear regressions examined associations between crime perceived by
      adolescents and crime reported to police and the outcomes of interest (BMI z
      scores, physical activity, and screen time). Models were stratified by gender and
      adjusted for age, race/ethnicity, socioeconomic status, and school. RESULTS: BMI
      was positively associated with perceived crime among girls and boys and with
      reported crime in girls. For girls, there was an association between higher
      perceived crime and increased screen time; for boys, between higher reported
      property crime and reduced physical activity. Perceived crime was associated with
      reported crime, both property and personal, in both genders. CONCLUSIONS: Few
      prior studies of adolescents have studied the association between both perceived
      and reported crime and BMI. Community-based programs for youth should consider
      addressing adolescents' safety concerns along with other perceived barriers to
      physical activity. Interventions targeting actual crime rates are also important.

PMID- 26206445
TI  - The Effectiveness of Cyberprogram 2.0 on Conflict Resolution Strategies and Self
      Esteem.
AB  - PURPOSE: In recent years, the problem of youth violence has been a cause of
      increasing concern for educational and mental health professionals worldwide. The
      main objective of the study was to evaluate experimentally the effects of an anti
      bullying/cyberbullying program (Cyberprogram 2.0; Piramide Publishing, Madrid,
      Spain) on conflict resolution strategies and self-esteem. METHODS: A randomly
      selected sample of 176 Spanish adolescents aged 13-15 years (93 experimental, 83
      control) was employed. The study used a repeated measures pretest-posttest design
      with a control group. Before and after the program (19 one-hour sessions), two
      assessment instruments were administered: the questionnaire for measuring
      conflict management message styles and the Rosenberg self-esteem scale. RESULTS:
      The analyses of covariance of the posttest scores confirmed that the program
      stimulated an increase of cooperative conflict resolution strategies, a decrease
      in aggressive and avoidant strategies, and an increase of self-esteem. The change
      was similar in both sexes. CONCLUSIONS: The study provides evidence of the
      effectiveness of Cyberprogram 2.0 to improve the capacity for conflict resolution
      and self-esteem. The discussion focuses on the importance of implementing
      programs to promote socioemotional development and to prevent violence.

PMID- 26206446
TI  - Family Economic Hardship, Corticotropin-Releasing Hormone Receptor Polymorphisms,
      and Depressive Symptoms in Rural African-American Youths.
AB  - PURPOSE: The purpose of this study was to use pooled data from two independent
      studies of rural African-American youths to test the moderation effect of the
      corticotropin-releasing hormone receptor 1 gene (CRHR1) on the link between
      family economic hardship and trajectories of depressive symptoms. METHODS: Two
      longitudinal studies were conducted involving African-Americans, aged 16 (N =
      474) and 18 (N = 419) years, who were randomly recruited in rural Georgia. Family
      economic hardship and youths' depressive symptoms were assessed four times across
      2.5 years. Genetic data also were collected. Haplotype analysis was performed on
      single-nucleotide polymorphisms of CRHR1; two haplotypes were aggregated to form
      a CRHR1 index. Growth curve models were executed to determine whether CRHR1
      moderated the link between Wave 1 family economic hardship and youths'
      development of depression. RESULTS: CRHR1 * family economic hardship interactions
      significantly predicted youths' depressive symptoms. When exposed to family
      economic hardship 1 standard deviation above the mean at Wave 1, youths who
      scored 0 on the CRHR1 index showed high and increasing depressive symptoms across
      time, whereas those who scored 2 on the index showed a decrease in depressive
      symptoms. CONCLUSIONS: The CRHR1 gene reduces the risk for depressive symptoms
      among youths living in families undergoing high levels of economic hardship.

PMID- 26206447
TI  - Adolescents' Use of Medical Marijuana: A Secondary Analysis of Monitoring the
      Future Data.
AB  - PURPOSE: To examine adolescents' annual use of medical marijuana and determine if
      legal medical marijuana users are at lower risk for frequent marijuana use and
      other substance use when compared to adolescents who use diverted medical
      marijuana or from an illicit source. METHODS: Public access Monitoring the Future
      data were used for this secondary analysis. The total weighted sample size was
      4394 12th graders. RESULTS: Users of medical marijuana and diverted medical
      marijuana had notable odds of using daily, using prescription drugs, and using
      illicit drugs among other substance use behaviors. Medical marijuana users had
      much higher odds of using medical marijuana because of being "hooked" when
      compared to diverted medical users and illicit users. CONCLUSION: This study is
      the first to provide nationally representative data on three groups of adolescent
      marijuana users. Although most adolescents use illicit sources, more adolescents
      appear to be using diverted medical marijuana, than using medical marijuana
      legally.

PMID- 26206448
TI  - Tracking Adolescents With Global Positioning System-Enabled Cell Phones to Study
      Contextual Exposures and Alcohol and Marijuana Use: A Pilot Study.
AB  - PURPOSE: Measuring activity spaces, places adolescents spend time, provides
      information about relations between contextual exposures and risk behaviors. We
      studied whether contextual exposures in adolescents' activity spaces differ from
      contextual risks present in residential contexts and examined relationships
      between contextual exposures in activity spaces and alcohol/marijuana use.
      METHODS: Adolescents (N = 18) aged 16-17 years carried global positioning system
      (GPS)-enabled smartphones for 1 week, with locations tracked. Activity spaces
      were created by connecting global positioning system points sequentially and
      adding buffers. Contextual exposure data (e.g., alcohol outlets) were connected
      to routes. Adolescents completed texts regarding behaviors. RESULTS: Adolescent
      activity spaces intersected 24.3 census tracts and contained nine times more
      alcohol outlets than that of residential census tracts. Outlet exposure in
      activity spaces was related to drinking. Low-socioeconomic status exposure was
      related to marijuana use. CONCLUSIONS: Findings suggest substantial differences
      between activity spaces and residential contexts and suggest that activity spaces
      are relevant for adolescent risk behaviors.

PMID- 26206449
TI  - Relationship between cell stiffness and stress fiber amount, assessed by
      simultaneous atomic force microscopy and live-cell fluorescence imaging.
AB  - Actomyosin stress fibers, one of the main components of the cell's cytoskeleton,
      provide mechanical stability to adherent cells by applying and transmitting
      tensile forces onto the extracellular matrix (ECM) at the sites of cell-ECM
      adhesion. While it is widely accepted that changes in spatial and temporal
      distribution of stress fibers affect the cell's mechanical properties, there is
      no quantitative knowledge on how stress fiber amount and organization directly
      modulate cell stiffness. We address this key open question by combining atomic
      force microscopy with simultaneous fluorescence imaging of living cells, and
      combine for the first time reliable quantitative parameters obtained from both
      techniques. We show that the amount of myosin and (to a lesser extent) actin
      assembled in stress fibers directly modulates cell stiffness in adherent mouse
      fibroblasts (NIH3T3). In addition, the spatial distribution of stress fibers has
      a second-order modulatory effect. In particular, the presence of either fibers
      located in the cell periphery, aligned fibers or thicker fibers gives rise to
      reinforced cell stiffness. Our results provide basic and significant information
      that will help design optimal protocols to regulate the mechanical properties of
      adherent cells via pharmacological interventions that alter stress fiber assembly
      or via micropatterning techniques that restrict stress fiber spatial
      organization.

PMID- 26206450
TI  - Cholinium-amino acid based ionic liquids: a new method of synthesis and physico
      chemical characterization.
AB  - In the present work we report the synthesis and physico-chemical characterization
      in terms of the viscosity and density of a wide series of cholinium-amino acid
      based room temperature ionic liquids ([Ch][AA] RTILs). 18 different amino acids
      were used to obtain 14 room temperature ILs. Among the most common AAs, only
      valine did not form an RTIL but it is a liquid above 80  degrees C. With respect
      to the methods reported in the literature we propose a synthesis based on
      potentiometric titration which has several advantages such as shorter preparation
      time, stoichiometry within +/-1%, very high yields (close to 100%), high
      reproducibility, and no use of organic solvents, thus being more environmentally
      friendly. We tried to prepare dianionic ILs with some AAs with two potentially
      ionisable groups but in all cases the salts were solids at room temperature. All
      the ILs were characterized by (1)H NMR to confirm the stoichiometry. Physico
      chemical properties such as density, viscosity, refractive index and conductivity
      were measured as a function of temperature and correlated with empirical
      equations. The values were compared with the data already reported in the
      literature for some [Ch][AA] ILs. The thermal expansion coefficient alphap and
      the molar volume Vm were also calculated from the experimental density values.
      Due to the high number of AAs explored and their structural heterogeneity we have
      been able to find some interesting correlations between the data obtained and the
      structural features of the AAs in terms of the alkyl chain length, hydrogen
      bonding ability, stacking and cyclization. Some parameters were also found to be
      in good agreement with those reported for other ILs. We think that these data can
      give an important contribution to the understanding of the structure-property
      relationship of ILs because they focused on the structural effect of the anions,
      while most data in the literature are focussed on the cations. 

PMID- 26206451
TI  - Sacrospinous hysteropexy versus vaginal hysterectomy with suspension of the
      uterosacral ligaments in women with uterine prolapse stage 2 or higher:
      multicentre randomised non-inferiority trial.
AB  - OBJECTIVE: To investigate whether uterus preserving vaginal sacrospinous
      hysteropexy is non-inferior to vaginal hysterectomy with suspension of the
      uterosacral ligaments in the surgical treatment of uterine prolapse. DESIGN:
      Multicentre randomised controlled non-blinded non-inferiority trial. SETTING: 4
      non-university teaching hospitals, the Netherlands. PARTICIPANTS: 208 healthy
      women with uterine prolapse stage 2 or higher requiring surgery and no history of
      pelvic floor surgery. INTERVENTIONS: Treatment with sacrospinous hysteropexy or
      vaginal hysterectomy with suspension of the uterosacral ligaments. The predefined
      non-inferiority margin was an increase in surgical failure rate of 7%. MAIN
      OUTCOME MEASURES: Primary outcome was recurrent prolapse stage 2 or higher of the
      uterus or vaginal vault (apical compartment) evaluated by the pelvic organ
      prolapse quantification system in combination with bothersome bulge symptoms or
      repeat surgery for recurrent apical prolapse at 12 months' follow-up. Secondary
      outcomes were overall anatomical recurrences, including recurrent anterior
      compartment (bladder) and/or posterior compartment (bowel) prolapse, functional
      outcome, complications, hospital stay, postoperative recovery, and sexual
      functioning. RESULTS: Sacrospinous hysteropexy was non-inferior for anatomical
      recurrence of the apical compartment with bothersome bulge symptoms or repeat
      surgery (n=0, 0%) compared with vaginal hysterectomy with suspension of the
      uterosacral ligaments (n=4, 4.0%, difference -3.9%, 95% confidence interval for
      difference -8.6% to 0.7%). At 12 months, overall anatomical recurrences,
      functional outcome, quality of life, complications, hospital stay, measures on
      postoperative recovery, and sexual functioning did not differ between the two
      groups. Five serious adverse events were reported during hospital stay. None was
      considered to be related to the type of surgery. CONCLUSIONS: Uterus preservation
      by sacrospinous hysteropexy was non-inferior to vaginal hysterectomy with
      suspension of the uterosacral ligaments for surgical failure of the apical
      compartment at 12 months' follow-up. TRIAL REGISTRATION: trialregister.nl
      NTR1866.

PMID- 26206452
TI  - Effect of Demographics on Excretion of Key Urinary Factors Related to Kidney
      Stone Risk.
AB  - OBJECTIVE: To investigate the effect of demographics including age and sex on
      excretion of 4 key urinary factors (calcium [Ca], magnesium [Mg], oxalate and
      uric acid [UA]) related to kidney stone risk. METHODS: Twenty-four-hour urine
      samples were collected from non-Hispanic white sibships in Rochester, MN. Height,
      weight, blood pressure, serum creatinine, and cystatin C were measured. Diet was
      assessed using the Viocare food frequency questionnaire. Effects of demographics
      and dietary elements on urinary excretions were evaluated in univariate,
      multivariate, and interaction models that included age, sex, and body mass index
      (BMI). RESULTS: Samples were available from 709 individuals. In multivariate
      models, sex was a significant predictor of all 4 urinary factors, age was
      significant for all but UA excretion, and serum creatinine was significant only
      for Ca and Mg excretion (P <.05). BMI or weight positively correlated with Mg,
      oxalate, and UA excretion (P <.05). Use of a thiazide diuretic (lower) and
      dietary protein (higher) were associated with Ca excretion, whereas dietary Ca
      was associated with higher Mg excretion. Urinary UA excretion increased with
      animal protein intake and cystatin C estimated glomerular filtration rate (eGFR)
      and was lower with concurrent loop diuretic use. Significant interaction effects
      on urinary UA excretion were observed for loop diuretic use and sex, eGFR and
      sex, age and animal protein intake, and BMI and eGFR (P <.05). CONCLUSION: Age
      and sex influence excretion of key urinary factors related to kidney stone risk
      and should be taken into account when evaluating kidney stone patients.

PMID- 26206453
TI  - N-acetylcysteine Ameliorates the Erectile Dysfunction Caused by Chronic
      Intermittent Hypoxia in Rats: Partly Involvement of Endoplasmic Reticulum Stress.
AB  - OBJECTIVE: To conduct a study using a rodent model of chronic intermittent
      hypoxia (CIH) to define whether endoplasmic reticulum stress (ERS) is involved in
      the CIH-induced apoptosis of penile tissue and erectile dysfunction (ED), and
      whether treatment with N-acetylcysteine (NAC) alleviates pathological variations
      in corpus cavernosa. Previous work has prompted that CIH acted as the major
      trigger linking obstructive sleep apnea syndrome and ED. MATERIALS AND METHODS:
      Five-month-old Sprague-Dawley male rats were subjected to 8 hours of intermittent
      hypoxia per day, with or without NAC for 5 weeks. Erectile function, apoptosis of
      penile tissue, levels of ERS-associated proapoptotic effectors, and nitric oxide
      (NO) and nitric oxide synthase (NOS) activity were determined. RESULTS: Treatment
      with NAC inhibited apoptosis of penile tissue, the expressions of ERS-related
      products: BIP, CHOP, caspase12, and Bax, NO, and endothelial NOS. Administration
      of NAC before CIH significantly improved the CIH-induced impaired erectile
      function. CONCLUSION: Our results show that pre-CIH NAC administration
      ameliorates the ED following CIH partly by alleviating CIH-induced ERS and cell
      apoptosis via regulating the expressions of BIP, CHOP, caspase12, and Bax.

PMID- 26206455
TI  - Reply to Frontino et al. Management of hyperosmolar hyperglycaemic state in
      adults with diabetes.

PMID- 26206456
TI  - Scaffold-based delivery of adipose tissue-derived stem cells in rat frozen-thawed
      ovarian autografts: preliminary studies in a rat model.
AB  - PURPOSE: This study aimed to evaluate whether a gelatin-based Gelfoam sponge is
      feasible as a scaffold for adipose tissue-derived stem cell (ASC) therapy in rat
      frozen-thawed ovarian autografts. METHODS: Two sets of studies were performed.
      The in vitro set evaluated ASCs' viability in the Gelfoam scaffold at different
      times of co-culturing (after 24, 48, 72, 96, and 120 h). The in vivo set used 20
      12-week-old adult female Wistar rats. Frozen-thawed ovarian grafts were treated
      with ASCs delivered in Gelfoam scaffolds immediately after an autologous
      retroperitoneal transplant (ASCs-GS, n = 10). The controls received Gelfoam with
      a culture medium (GS, n = 10). Assessment of graft quality was conducted by
      vaginal smears (until euthanasia on the 30th postoperative day), histological
      analyses, follicular density, and viability and fibrosis. Immunohistochemical
      staining for VEGF-A expression, vascular network (vWF), apoptosis (caspase-3 and
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)),
      cell proliferation (Ki-67), and hormone receptors (estrogen and progesterone)
      were performed. RESULTS: The cells remained viable in Gelfoam for up to 120 h of
      co-culturing. The graft morphology was similar among the groups. ASC therapy
      promoted the earlier resumption of the estrous phase (GS 16.6 +/- 3 vs. ASCs-GS
      12.8 +/- 1.3 days) and enhanced estrogen receptors compared with the controls (p
      < 0.05) without interfering with the quantity and viability of the ovarian
      follicles, fibrosis, endothelial cells, VEGF immunoexpression, apoptosis, or cell
      proliferation (p > 0.05). CONCLUSION: The Gelfoam scaffold could be a feasible
      and safe non-invasive technique for ASC delivery in the treatment of frozen
      thawed ovarian autografts. Future studies should evaluate the real benefit of
      this treatment on the survival and endocrine activity of the graft.

PMID- 26206458
TI  - B-Cells and the Use of Non-Human Primates for Evaluation of HIV Vaccine
      Candidates.
AB  - The RV144 clinical trial in Thailand associated vaccine-induced antibodies with
      protective efficacy, leading to a focus in HIV vaccine research on protective
      antibody induction. This has necessitated greater understanding of B cell biology
      in humans as well as non-human primates (NHP), the principle animal model for pre
      clinical HIV/SIV vaccine research. This review covers development and maturation
      of NHP B cells within the framework of current knowledge of human and murine B
      cells. Identification of many NHP B cell subpopulations is now possible, although
      consensus is lacking in some cases, and better distinction of some populations is
      still needed. Elucidation of mechanisms that control germinal center maintenance,
      selection of B cells into the memory cell pool, and differentiation of B cells
      into long-lived plasma cells remains critical for improving vaccine design. B
      cell dysfunction occurs during both HIV and SIV infection. Whether the processes
      leading to this impairment are identical in humans and NHP is not known.
      Uncovering the mechanisms involved could lead to improved treatment regimens. The
      SIV/NHP model effectively mimics HIV infection of people, but key differences
      between NHP and humans in antibody characteristics such as glycosylation and
      structure may lead to unexpected outcomes in pre-clinical studies. Important new
      areas for investigation include the role of B cell cytokines in the immune system
      and the impact of the microbiome on B cell development and maturation. Enhanced
      knowledge of B cells in NHP as well as humans should enable improved vaccine
      design, leading to induction of potent, long-lasting protective antibodies. 

PMID- 26206457
TI  - Is the presence of an uncleaved embryo on day 3 a useful predictor of outcomes
      following day 5 transfer?
AB  - PURPOSE: This study aimed to determine whether the presence of an uncleaved
      embryo on day 3 is predictive of cycle outcome after day 5 transfer (D5 ET).
      METHODS: In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)
      cycles from January 2013 to November 2014 with D5 ET were analyzed for the
      presence of at least one uncleaved embryo on day 3 (D3). Each index cycle (n =
      70) was compared with two matched control cycles without uncleaved embryos. The
      main outcome measures included embryo quality, implantation rate, and clinical
      pregnancy rate. RESULTS: Fifty-nine of 3896 total embryos in this study were
      uncleaved on D3 (1.5 %). Cycles with uncleaved embryos had more oocytes retrieved
      (20.6 vs. 17.5), lower proportions of good quality embryos on D3 (52.4 vs. 66.1
      %), and fewer usable embryos (transferred or frozen) on D5 (42.4 vs. 50.8 %).
      However, there were no significant differences in the incidence of cycles with a
      positive hCG, or in the rates of implantation, clinical pregnancy, or live birth.
      CONCLUSIONS: Although an uncleaved embryo on D3 is associated with reduced
      conversion of sibling embryos to the blastocyst stage on D5, overall quality of
      those embryos forming blastocysts is not markedly decreased and clinical outcomes
      are not compromised.

PMID- 26206459
TI  - Use of Model-Based Nutrient Feeding for Improved Production of Artemisinin by
      Hairy Roots of Artemisia Annua in a Modified Stirred Tank Bioreactor.
AB  - Artemisinin has been indicated to be a potent drug for the cure of malaria. Batch
      growth and artemisinin production kinetics of hairy root cultures of Artemisia
      annua were studied under shake flask conditions which resulted in accumulation of
      12.49 g/L biomass and 0.27 mg/g artemisinin. Using the kinetic data, a
      mathematical model was identified to understand and optimize the system behavior.
      The developed model was then extrapolated to design nutrient feeding strategies
      during fed-batch cultivation for enhanced production of artemisinin. In one of
      the fed-batch cultivation, sucrose (37 g/L) feeding was done at a constant feed
      rate of 0.1 L/day during 10-15 days, which led to improved artemisinin
      accumulation of 0.77 mg/g. The second strategy of fed-batch hairy root
      cultivation involved maintenance of pseudo-steady state sucrose concentration
      (20.8 g/L) during 10-15 days which resulted in artemisinin accumulation of 0.99
      mg/g. Fed-batch cultivation (with the maintenance of pseudo-steady state of
      substrate) of Artemisia annua hairy roots was, thereafter, implemented in
      bioreactor cultivation, which featured artemisinin accumulation of 1.0 mg/g
      artemisinin in 16 days of cultivation. This is the highest reported artemisinin
      yield by hairy root cultivation in a bioreactor.

PMID- 26206460
TI  - The fat droplet in hepatocellular ballooning and implications for scoring
      nonalcoholic steatohepatitis therapeutic response.

PMID- 26206461
TI  - Giant coronary sinus in rheumatic heart disease: a rare case presentation.

PMID- 26206462
TI  - Percutaneous closure of giant left appendages.

PMID- 26206463
TI  - Strain and left ventricular volumes for predicting cardiotoxicity: a life-saving
      approach in anthracycline cancer treatment?

PMID- 26206465
TI  - Effect of antibiotics on FDG-PET/CT imaging of prosthetic heart valve
      endocarditis.

PMID- 26206464
TI  - Typical blood pressure response during dobutamine stress echocardiography of
      patients without known cardiovascular disease who have normal stress
      echocardiograms.
AB  - AIMS: Blood pressure (BP) responses during dobutamine stress echocardiography
      (DSE) have not been systematically studied. Consequently, it is not known what
      constitutes a normal or an abnormal BP response to dobutamine stress. We sought
      to define the typical BP response during DSE of patients not known to have
      cardiovascular disease. METHODS AND RESULTS: Of 24 134 patients who underwent DSE
      from November 2003 to December 2012 at Mayo Clinic, Rochester, MN, 2968 were
      selected for inclusion in this retrospective study. Excluded were patients with a
      history of hypertension, diabetes, or coronary artery disease, and those taking
      vasoactive medications. Patients who had baseline and/or stress-induced wall
      motion abnormalities were also excluded. The distribution of the study
      population's BP responses during DSE was Gaussian; we defined cut-point values
      for normative BP responses at 2 SD for each decade of age and for the whole study
      population. During DSE, systolic BP (SBP) increased from baseline to peak stress
      (Delta +2.9 +/- 24 mmHg, P < 0.0001) and diastolic BP (DBP) decreased (Delta -7.4
      +/- 14 mmHg). BP changes were age and sex dependent; men and younger patients had
      greater DeltaSBP and lesser DeltaDBP, compared with women and older patients.
      Patients who received atropine had higher peak BP values than patients who did
      not receive atropine, due to greater DeltaSBP (+7.4 +/- 26 vs. -0.5 +/- 22 mmHg,
      P < 0.0001) and lesser DeltaDBP (-4 +/- 14 vs. -9.7 +/- 12 mmHg, P < 0.0001).
      This atropine effect was present in men and women, and was more pronounced in
      younger patients. The normative peak SBP values ranged from 82 to 182 mmHg.
      CONCLUSION: BP responses during DSE vary and depend on patients' age, gender, and
      the use of atropine. We describe the typical BP responses seen during DSE and
      report normative reference values, which can be used for defining normal and
      abnormal BP responses to dobutamine stress.

PMID- 26206467
TI  - Cardiac sarcoidosis with visually normal wall motion: role of cardiac MRI, FDG
      PET, and strain echocardiography.

PMID- 26206466
TI  - Differential response of LV sublayer twist during dobutamine stress
      echocardiography as a novel marker of contractile reserve after acute myocardial
      infarction: relationship with follow-up LVEF improvement.
AB  - AIMS: Dobutamine stress echocardiography (DSE) is frequently performed to assess
      left ventricular (LV) contractile reserve in patients following myocardial
      infarction (STEMI). Given that resting LV sublayer twist assessment has been
      proposed as a marker of infarct transmurality, this study aimed to investigate
      whether response of LV subepicardial twist on DSE represents a novel quantitative
      marker of contractile reserve. METHODS AND RESULTS: First STEMI patients treated
      with primary percutaneous coronary intervention with a resting wall motion
      abnormality in greater than or equal to two segment(s) at 3 months who underwent
      full protocol DSE were included. Two-dimensional speckle-tracking was used to
      calculate LV subepi- and subendocardial twist-defined as the net difference (in
      degrees) of apical and basal rotation for each sublayer-at rest and peak-dose
      stages. Primary end point was a >=5% absolute LV ejection fraction (LVEF)
      improvement between 3 and 6 months. In total, 61 patients (mean age 61 +/- 12,
      87% male) were included, of whom 48% (n = 29) demonstrated follow-up LVEF
      improvement. Mean change in both LV subepicardial (DeltaLVsubepi) twist (2.4 +/-
      3.0 vs. 0.00 +/- 2.0 degrees , P = 0.001) and LV subendocardial (DeltaLVsubendo)
      twist (2.7 +/- 4.5 vs. 0.25 +/- 4.5 degrees , P = 0.04) from rest to peak was
      significantly higher in LVEF improvers. DeltaLVsubepi (odds ratio, OR 1.5, 95%
      confidence interval, CI 1.1-2.0, P = 0.007), but not DeltaLVsubendo (OR 1.1, 95%
      CI 0.99-1.3, P = 0.07), twist was independently associated with follow-up LVEF
      improvement following adjustment for baseline LVEF and beta-blockade. CONCLUSION:
      In post-STEMI patients with resting regional dysfunction, the response of LV
      subepicardial twist on DSE is associated with follow-up LV function improvement,
      suggesting recruitment in subepicardial function following STEMI reflects greater
      extent of contractile reserve.

PMID- 26206468
TI  - [Not Available].

PMID- 26206470
TI  - Condition-dependent movement and dispersal in experimental metacommunities.
AB  - Dispersal and the underlying movement behaviour are processes of pivotal
      importance for understanding and predicting metapopulation and metacommunity
      dynamics. Generally, dispersal decisions are condition-dependent and rely on
      information in the broad sense, like the presence of conspecifics. However,
      studies on metacommunities that include interspecific interactions generally
      disregard condition-dependence. Therefore, it remains unclear whether and how
      dispersal in metacommunities is condition-dependent and whether rules derived
      from single-species contexts can be scaled up to (meta)communities. Using
      experimental protist metacommunities, we show how dispersal and movement depend
      on and are adjusted by the strength of interspecific interactions. We found that
      the predicting movement and dispersal in metacommunities requires knowledge on
      behavioural responses to intra- and interspecific interaction strengths.
      Consequently, metacommunity dynamics inferred directly from single-species
      metapopulations without taking interspecific interactions into account are likely
      flawed. Our work identifies the significance of condition-dependence for
      understanding metacommunity dynamics, stability and the coexistence and
      distribution of species.

PMID- 26206469
TI  - Stress and biological aging: A double-edged sword.
AB  - It is well accepted that aging is the basis of most degenerative diseases in the
      elderly. Biological aging is characterized by a gradual accumulation of cellular
      and molecular defects. An important cause of defects is intense stress, such as
      oxidative or glycotoxic stress. Genes affecting cellular and organismal longevity
      are frequently associated with the regulation of cellular anti-oxidative defense
      and/or with repair functions. Damage, combined with an age-dependent decline in
      defense and repair systems, results in disturbed homeostasis, leading to aging
      and diseases. Whereas intense stress induces premature aging, mild stress can
      induce adaptive processes, stimulating the expression of genetic repair/defense
      systems, which positively influences life span. 

PMID- 26206472
TI  - Three new HLA-DQB1 alleles - DQB1*03:113, DQB1*06:02:15 and DQB1*06:129.
AB  - Three novel HLA-DQB1 alleles were found after sequence-based typing of 3558
      random UK European routine blood donors. 

PMID- 26206471
TI  - Evaluation of the Utility of a Transition Workbook in Preparing Adolescent and
      Young Adult Cancer Survivors for Transition to Adult Services: A Pilot Study.
AB  - Transition to adult care for adolescent and young adult survivors is challenging
      and is inclusive of several factors like knowledge and developmental, emotional,
      and social status of survivors and parents. This pilot study addressed the
      feasibility of a transition workbook, a method of preparing adolescent and young
      adults to transition to adult care. Using a mixed methods design, investigators
      also measured transition worry and readiness in 30 survivors. Support was
      provided throughout a 6-month period as survivors and parents completed the
      workbook. The workbook included sections about the treatment history of
      survivors, when and who to call for worrisome symptoms, prescriptions and
      insurance, educational goals for health practices and how to get there, and
      independent living. Twenty survivors completed the study and reported greater
      worry about leaving pediatric oncology but indicated the need to make changes to
      transition to adult care. Ambiguity and intimidation about transitioning to adult
      providers and comfort in pediatric setting were themes expressed by survivors.
      Results indicate the need for adult/pediatric collaborative transition programs
      using various standardized methods of addressing transition readiness and
      evaluation. 

PMID- 26206473
TI  - Utilization of ancient permafrost carbon in headwaters of Arctic fluvial
      networks.
AB  - Northern high-latitude rivers are major conduits of carbon from land to coastal
      seas and the Arctic Ocean. Arctic warming is promoting terrestrial permafrost
      thaw and shifting hydrologic flowpaths, leading to fluvial mobilization of
      ancient carbon stores. Here we describe (14)C and (13)C characteristics of
      dissolved organic carbon from fluvial networks across the Kolyma River Basin
      (Siberia), and isotopic changes during bioincubation experiments. Microbial
      communities utilized ancient carbon (11,300 to >50,000 (14)C years) in permafrost
      thaw waters and millennial-aged carbon (up to 10,000 (14)C years) across
      headwater streams. Microbial demand was supported by progressively younger ((14)C
      enriched) carbon downstream through the network, with predominantly modern carbon
      pools subsidizing microorganisms in large rivers and main-stem waters. Permafrost
      acts as a significant and preferentially degradable source of bioavailable carbon
      in Arctic freshwaters, which is likely to increase as permafrost thaw intensifies
      causing positive climate feedbacks in response to on-going climate change. 

PMID- 26206474
TI  - The necessity of an observational study on the interactions between allergic
      history and citrus fruit intake for the prevention of pancreatic cancer.
AB  - While the main product of Jeju Island is citrus fruit and the prevalence of
      atopic dermatitis among the students who live there is relatively high, the
      incidence of pancreatic cancer is lowest in Korea. Systematic reviews reporting
      allergic history and intake of citrus fruit as protective factors against
      pancreatic cancer (PCC) were published in 2005 and 2008, respectively. Although
      there were discrepancies in the results of the subgroup analyses between case
      control and cohort studies, it is necessary to evaluate an interaction effect
      between allergic history and intake of citrus fruits on PCC risk. 

PMID- 26206475
TI  - A bioinspired catalytic aerobic oxidative C-H functionalization of primary
      aliphatic amines: synthesis of 1,2-disubstituted benzimidazoles.
AB  - Aerobic oxidative C?H functionalization of primary aliphatic amines has been
      accomplished with a biomimetic cooperative catalytic system to furnish 1,2
      disubstituted benzimidazoles that play an important role as drug discovery
      targets. This one-pot atom-economical multistep process, which proceeds under
      mild conditions, with ambient air and equimolar amounts of each coupling partner,
      constitutes a convenient environmentally friendly strategy to functionalize non
      activated aliphatic amines that remain challenging substrates for non-enzymatic
      catalytic aerobic systems. 

PMID- 26206476
TI  - Heart dose reduction in breast cancer treatment with simultaneous integrated
      boost: Comparison of treatment planning and dosimetry for a novel hybrid
      technique and 3D-CRT.
AB  - OBJECTIVE: The present study compares in silico treatment plans of clinically
      established three-dimensional conformal radiotherapy (3D-CRT) with a hybrid
      technique consisting of intensity-modulated radiotherapy (IMRT) and volumetric
      modulated arc radiotherapy (VMAT) during normally fractionated radiation of
      mammary carcinomas with simultaneous integrated boost on the basis of dose-volume
      histogram (DVH) parameters. PATIENTS AND METHODS: Radiation treatment planning
      was performed with a hybrid and a 3D-CRT treatment plan for 20 patients. Hybrid
      plans were implemented with two tangential IMRT fields and a VMAT field in the
      angular range of the tangents. Verification of the plan was performed with a
      manufacturer-independent measurement system consisting of a detector array and
      rotation unit. RESULTS: The mean values of the heart dose for the entire patient
      collective were 3.6 +/- 2.5 Gy for 3D-CRT and 2.9 +/- 2.1 Gy for the hybrid
      technique (p < 0.01). For the left side (n = 10), the mean values for the left
      anterior descending artery were 21.8 +/- 7.4 Gy for 3D-CRT and 17.6 +/- 7.4 Gy
      for the hybrid technique (p < 0.01). The mean values of the ipsilateral lung were
      11.9 +/- 1.6 Gy for 3D-CRT and 10.5 +/- 1.3 Gy for the hybrid technique (p <
      0.01). Calculated dose distributions in the hybrid arm were in good accordance
      with measured dose (on average 95.6 +/- 0.5 % for gamma < 1 and 3 %/3 mm). The
      difference of the mean treatment time per fraction was 7 s in favor of 3D-CRT.
      CONCLUSION: Compared with the established 3D-CRT technique, the hybrid technique
      allows for a decrease in dose, particularly of the mean heart and lung dose with
      comparable target volume acquisition and without disadvantageous low-dose load of
      contralateral structures. Uncomplicated implementation of the hybrid technique
      was demonstrated in this context. The hybrid technique combines the advantages of
      tangential IMRT with the superior sparing of organs at risk by VMAT.

PMID- 26206477
TI  - Interventions for Increasing Alcohol Treatment Utilization Among Patients with
      Alcohol Use Disorders from Emergency Departments: A Systematic Review.
AB  - AIM: Alcohol use disorders (AUDs) are characterized by low treatment coverage.
      Emergency departments (EDs) have great potential to increase alcohol treatment
      coverage. While ED-based brief interventions (BIs) are rarely effective for
      reducing alcohol use and related consequences in people with AUDs, utilization of
      formal alcohol treatment has been demonstrated to be useful. Thus we conducted a
      systematic review to determine efficacious interventions for increasing
      subsequent alcohol treatment from EDs. METHODS: A systematic search of the
      literature up to 31 December 2013 was undertaken in three electronic databases:
      PubMed, PsycINFO and The Cochrane Library. Only randomized controlled trials
      (RCTs), controlled clinical trials (CCTs) and non-randomized controlled trials
      (NRCTs) were included. A meta-analysis was judged inappropriate because of
      substantial discrepancies in term of interventions' characteristics across
      studies. RESULTS: From the 2182 identified records, 7 studies (4RCTs, 2 CCTs,
      1NRCT) met inclusion criteria. Onsite brief advice (BA) was found efficacious in
      comparison to no active control condition, but no evidence of efficacy was found
      when compared to active control conditions. Referral to post-discharge BIs was
      not found efficacious either used alone or in addition to onsite BA. There is
      evidence, albeit limited, suggesting that more intensive interventions, such as
      referral to extended post-discharge interventions and onsite extended BI, might
      be useful. CONCLUSIONS: Based on the available evidence, onsite BA with leaflets
      appears to be the minimum level of intervention since it enables to actively
      intervene while fitting in the time concerns experienced in EDs. Further research
      is needed to confirm these findings given the limited quantity and quality of
      existing data and to determine whether more intensive interventions could
      actually be useful.

PMID- 26206479
TI  - Can UK NHS research ethics committees effectively monitor publication and outcome
      reporting bias?
AB  - BACKGROUND: Publication and outcome reporting bias is often caused by researchers
      selectively choosing which scientific results and outcomes to publish. This
      behaviour is ethically significant as it distorts the literature used for future
      scientific or clinical decision-making. This study investigates the
      practicalities of using ethics applications submitted to a UK National Health
      Service (NHS) research ethics committee to monitor both types of reporting bias.
      METHODS: As part of an internal audit we accessed research ethics database
      records for studies submitting an end of study declaration to the Hampshire A
      research ethics committee (formerly Southampton A) between 1st January 2010 and
      31st December 2011. A literature search was used to establish the publication
      status of studies. Primary and secondary outcomes stated in application forms
      were compared with outcomes reported in publications. RESULTS: Out of 116 studies
      the literature search identified 57 publications for 37 studies giving a
      publication rate of 32%. Original Research Ethics Committee (REC) applications
      could be obtained for 28 of the published studies. Outcome inconsistencies were
      found in 16 (57%) of the published studies. CONCLUSIONS: This study showed that
      the problem of publication and outcome reporting bias is still significant in the
      UK. The method described here demonstrates that UK NHS research ethics committees
      are in a good position to detect such bias due to their unique access to original
      research protocols. Data gathered in this way could be used by the Health
      Research Authority to encourage higher levels of transparency in UK research.

PMID- 26206478
TI  - Molecular Analysis of Pediatric Oligodendrogliomas Highlights Genetic Differences
      with Adult Counterparts and Other Pediatric Gliomas.
AB  - Oligodendroglioma represents a distinctive neoplasm in adults but similar
      neoplasms occur rarely in children. We studied 20 cases of pediatric
      oligodendroglioma by SNP array (median age 9 years, range 1-19; 15 grade II and 5
      grade III). Cytogenetic abnormalities were present in 8 (53%) grade II and all
      five anaplastic oligodendrogliomas. Most changes were in the form of deletion and
      copy neutral loss of heterozygosity (LOH). The most common abnormality was 1p
      deletion (n = 5). Whole arm 1p19q co-deletion was present in three cases from
      adolescent patients and 9p loss in 3, including one low-grade oligodendroglioma
      with CDKN2A homozygous deletion. Common losses were largely limited to the
      anaplastic subset (n = 5) and included 3q29 (n = 3), 11p (n = 3), 17q (n = 3), 4q
      (n = 2), 6p (n = 2), 13q (n = 2), 14q (n = 2), 17p (n = 2) and whole Ch 18 loss
      (n = 2). Gains were non-recurrent except for whole Ch 7 (n = 2) and gain on 12q
      (n = 2) including the MDM2 locus. Possible germ line LOH (or uniparental disomy)
      was present in seven cases (35%), with one focal abnormality (22q13.1-13.2) in
      two. BRAF-KIAA1549 fusions and BRAF p.V600E mutations were absent (n = 13 and 8).
      In summary, cytogenetic alterations in pediatric oligodendrogliomas are
      characterized mostly by genomic losses, particularly in anaplastic tumors.

PMID- 26206480
TI  - An infant with a hyperlucent chest mass: An unexpected diagnosis.
AB  - INTRODUCTION: We report an unusual finding of pneumatocele in an infant. CASE
      REPORT: A previously well four month old presented with worsening respiratory
      distress over 6 weeks. He had no antecedent signs or symptoms of respiratory
      infection. Chest radiograph demonstrated a lucent hemithorax concerning for
      tension pneumothorax. Urgent needle decompression was performed. Chest CT showed
      a persistent dominant macrocyst on the left. Thoracotomy revealed a large cystic
      lesion necessitating a left lower lobectomy. Histopathology was consistent with a
      pneumatocele. He remains clinically stable at 16 months postoperatively.
      DISCUSSION: Pneumatocele is a rare cause of cystic lung disease presenting in
      infancy. The young age at onset, prolonged symptoms without preceding infection,
      and tension physiology in our patient are unique.

PMID- 26206482
TI  - Are epidemiological data on lymphoma incidence comparable? Results from an
      application of the coding recommendations of WHO, InterLymph, ENCR and SEER to a
      cancer registry dataset.
AB  - PURPOSE: The REAL classification of 1994 and the subsequent WHO classification of
      2001 can be considered a breakthrough of international harmonization of lymphoma
      characterization, terminology and codification. These efforts promised to produce
      internationally comparable cancer registry data in the future. However, in
      practice discrepancies of usage of these classifications occurred which hamper
      comparability of registration outcome and must be taken into account by
      epidemiologic research. METHODS: In order to analyze such discrepancies, we used
      the assignment recommendations of the World Health Organisation 2008, InterLymph
      2010, European Network of Cancer Registry 2009 and Surveillance, Epidemiology,
      and End Results Program 2010 for lymphoid neoplasms in groups and major NHL
      groups. We used data of the Federal State Cancer Registry of Baden-Wuerttemberg
      2010-2011 to test differences in incidence outcome when evaluated according to
      the different recommendations of these institutions. RESULTS: Depending on the
      recommendations of the above institutions, extraction of lymphoid neoplasms
      provided 4021, 4295, 3873 and 3848 incident cases, respectively. Case numbers for
      some major NHL groups diverge substantially by recommendation. CONCLUSIONS:
      Epidemiologists must be aware of potential discrepancies in coding conventions of
      cancer registries and have to consider them in comparative data analyses. Cancer
      registries should make transparent which recommendations were applied for
      lymphoma codification, currently and in the past. Conversion rules should be
      offered to ascertain proper mapping of lymphoma entities which were coded under
      varying coding practices over time.

PMID- 26206484
TI  - Preparation and Electrochemical Properties of Tin-Iron-Carbon Nanocomposite as
      the Anode of Lithium-Ion Batteries.
AB  - Tin-iron-carbon nanocomposite is successfully prepared by a sol-gel method
      followed by a chemical vapor deposition (CVD) process with acetylene gas as the
      carbon source. The structural properties, morphology, and electrochemical
      performances of the nanocomposite are comprehensively studied in comparison with
      those properties of tin-carbon and iron-carbon nanocomposites. Sheet-like carbon
      architecture and different carbon contents are induced thanks to the catalytic
      effect of iron during CVD. Among three nanocomposites, tin-iron-carbon
      demonstrates the highest reversible capacity of 800 mA h g(-1) with 96.9%
      capacity retention after 50 cycles. It also exhibits the best rate capability
      with a discharge capacity of 420 mA h g(-1) at a current density of 1000 mA g(
      1). This enhanced performance is strongly related to the carbon morphology and
      content, which can not only accommodate the large volume change, but also improve
      the electronic conductivity of the nanocomposite. Hence, the tin-iron-carbon
      nanocomposite is expected to be a promising anode for lithium-ion batteries.

PMID- 26206485
TI  - Do Prosecutors Use Interview Instructions or Build Rapport with Child Witnesses?
AB  - This study examined the quality of interview instructions and rapport-building
      provided by prosecutors to 168 children aged 5-12 years testifying in child
      sexual abuse cases, preceding explicit questions about abuse allegations.
      Prosecutors failed to effectively administer key interview instructions, build
      rapport, or rely on open-ended narrative producing prompts during this early
      stage of questioning. Moreover, prosecutors often directed children's attention
      to the defendant early in the testimony. The productivity of different types of
      wh- questions varied, with what/how questions focusing on actions being
      particularly productive. The lack of instructions, poor quality rapport-building,
      and closed-ended questioning suggest that children may not be adequately prepared
      during trial to provide lengthy and reliable reports to their full ability.

PMID- 26206483
TI  - Valproic acid (VPA) inhibits the epithelial-mesenchymal transition in prostate
      carcinoma via the dual suppression of SMAD4.
AB  - PURPOSES: The epithelial-mesenchymal transition (EMT) plays an important role in
      cancer metastasis. Previous studies have reported that valproic acid (VPA)
      suppresses prostate carcinoma (PCa) cell metastasis and down-regulates SMAD4
      protein levels, which is the key molecule in TGF-beta-induced EMT. However, the
      correlation between VPA and the EMT in PCa remains uncertain. METHODS: Markers of
      the EMT in PCa cells and xenografts were molecularly assessed after VPA
      treatment. The expression and mono-ubiquitination of SMAD4 were also analyzed.
      After transfection with plasmids that express SMAD4 or short hairpin RNA for
      SMAD4 down-regulation, markers of EMT were examined to confirm whether VPA
      inhibits the EMT of PCa cells through the suppression of SMAD4. RESULTS: VPA
      induced the increase in E-cadherin (p < 0.05), and the decrease in N-cadherin (p
      < 0.05) and Vimentin (p < 0.05), in PCa cells and xenografts. SMAD4 mRNA and
      protein levels were repressed by VPA (p < 0.05), whereas the level of mono
      ubiquitinated SMAD4 was increased (p < 0.05). SMAD4 knockdown significantly
      increased E-cadherin expression in PC3 cells, but SMAD4 over-expression abolished
      the VPA-mediated EMT-inhibitory effect. CONCLUSIONS: VPA inhibits the EMT in PCa
      cells via the inhibition of SMAD4 expression and the mono-ubiquitination of
      SMAD4. VPA could serve as a promising agent in PCa treatment, with new strategies
      based on its diverse effects on posttranscriptional regulation.

PMID- 26206486
TI  - A Multicenter Cohort Study of Inferior Vena Cava Filter Use in Children.
AB  - BACKGROUND: To describe inferior vena cava (IVC) filter use in pediatric patients
      admitted to U.S. children's hospitals and to determine factors associated with
      prophylactic placement. PROCEDURE: This retrospective multicenter cohort study
      utilized data from the Pediatric Health Information Systems (PHIS) administrative
      database, with 44 participating children's hospitals. Subjects included for
      analysis were less than 21 years of age, admitted to a PHIS hospital between
      January 1, 2004 and December 31, 2012 and had a procedure code for IVC filter
      placement. ICD-9-CM discharge codes were used to identify subjects with a venous
      thromboembolism (VTE). Pharmaceutical billing codes were used to identify
      anticoagulation use. RESULTS: During this 9-year-study period, 276 subjects met
      the inclusion criteria. The median age of subjects was 15 years (range 1 month-20
      years). Subjects had an ICD-9-CM code for VTE 76% of the time and were started on
      anticoagulation after IVC filter placement 77% of the time. The mean number of
      IVC filters placed per year was 6 per 100,000 admissions (SD-1.4), which was
      constant throughout the study period (P = 0.12). The median number of filters
      placed by center was 4.5 (range 0-32). In multivariate analysis, subjects
      undergoing orthopedic surgery were more likely to have prophylactic placement of
      an IVC filter (OR 4.5; 95%CI 1.8-11). CONCLUSIONS: IVC filter placement in
      pediatric patients remains a rare event and is most common in adolescents. Unlike
      in adults, pediatric IVC filter placement does not appear to be increasing over
      time and is predominantly used in the setting of a venous thrombotic event.

PMID- 26206487
TI  - Mutational Analysis of the Putative High-Affinity Propofol Binding Site in Human
      beta3 Homomeric GABAA Receptors.
AB  - Propofol is a sedative and anesthetic agent that can both activate GABA(A)
      receptors and potentiate receptor activation elicited by submaximal
      concentrations of the transmitter. A recent modeling study of the beta3 homomeric
      GABA(A) receptor postulated a high-affinity propofol binding site in a
      hydrophobic pocket in the middle of a triangular cleft lined by the M1 and M2
      membrane-spanning domains of one subunit and the M2 domain of the neighboring
      subunit. The goal of the present study was to gain functional evidence for the
      involvement of this pocket in the actions of propofol. Human beta3 and
      alpha1beta3 receptors were expressed in Xenopus oocytes, and the effects of
      substitutions of selected residues were probed on channel activation by propofol
      and pentobarbital. The data demonstrate the vital role of the beta3(Y143),
      beta3(F221), beta3(Q224), and beta3(T266) residues in the actions of propofol but
      not pentobarbital in beta3 receptors. The effects of beta3(Y143W) and
      beta3(Q224W) on activation by propofol are likely steric because propofol analogs
      with less bulky ortho substituents activated both wild-type and mutant receptors.
      The T266W mutation removed activation by propofol in beta3 homomeric receptors;
      however, this mutation alone or in combination with a homologous mutation (I271W)
      in the alpha1 subunit had almost no effect on activation properties in
      alpha1beta3 heteromeric receptors. We hypothesize that heteromeric alpha1beta3
      receptors can be activated by propofol interactions with beta3-beta3, alpha1
      beta3, and beta3-alpha1 interfaces, but the exact locations of the binding site
      and/or nature of interactions vary in different classes of interfaces.

PMID- 26206489
TI  - Variable-angle high-angle annular dark-field imaging: application to three
      dimensional dopant atom profiling.
AB  - Variable-angle high-angle annular dark-field (HAADF) imaging in scanning
      transmission electron microscopy is developed for precise and accurate
      determination of three-dimensional (3D) dopant atom configurations. Gd-doped
      SrTiO3 films containing Sr columns containing zero, one, or two Gd dopant atoms
      are imaged in HAADF mode using two different collection angles. Variable-angle
      HAADF significantly increases both the precision and accuracy of 3D dopant
      profiling. Using image simulations, it is shown that the combined information
      from the two detectors reduces the uncertainty in the dopant depth position
      measurement and can uniquely identify certain atomic configurations that are
      indistinguishable with a single detector setting. Additional advances and
      applications are discussed. 

PMID- 26206488
TI  - Adenylyl Cyclase 5 Regulation by Gbetagamma Involves Isoform-Specific Use of
      Multiple Interaction Sites.
AB  - Adenylyl cyclase (AC) converts ATP into cyclic AMP (cAMP), an important second
      messenger in cell signaling. Heterotrimeric G proteins and other regulators are
      important for control of AC activity. Depending on the AC isoform, Gbetagamma
      subunits can either conditionally stimulate or inhibit cAMP synthesis. We
      previously showed that the Galphas-betagamma heterotrimer binds to the N terminus
      (NT) of type 5 AC (AC5). We now show that Gbetagamma binds to the NT of a wide
      variety of AC isoforms. We hypothesized that Gbetagamma/AC5 interactions
      involving inactive heterotrimer and Gbetagamma stimulation of AC5 were separable
      events. Mutations of the Gbetagamma "hotspot" show that this site is necessary
      for AC5 stimulation but not for interactions with the first 198 aa of AC5NT,
      which is a G protein scaffolding site. This contrasts with AC6, where the
      Gbetagamma hotspot is required for both interactions with AC6NT and for
      stimulation of AC6. Additionally, the SIGK hotspot peptide disrupts Gbetagamma
      regulation of AC isoforms 1, 2, and 6, but not AC5. Gbetagamma also binds the
      C1/C2 catalytic domains of AC5 and AC6. Finally, cellular interactions with full
      length AC5 depend on multiple sites on Gbetagamma. This suggests an isoform
      specific mechanism in which bound Gbetagamma at the AC5NT is ideally situated for
      spatiotemporal control of AC5. We propose Gbetagamma regulation of AC involves
      multiple binding events, and the role of the AC NT for mechanisms of regulation
      by heterotrimeric G protein subunits is isoform-specific. 

PMID- 26206490
TI  - Factors Associated with Geographic Variation in Psychiatric Prescription Drug
      Expenditures Among Medicaid Beneficiaries.

PMID- 26206491
TI  - Non-linear optical response by functionalized gold nanospheres: identifying
      design principles to maximize the molecular photo-release.
AB  - In a recent study by Voliani et al. [Small, 2011, 7, 3271], the electromagnetic
      field enhancement in the vicinity of the gold nanoparticle surface has been
      exploited to achieve photocontrolled release of a molecular cargo conjugated to
      the nanoparticles via 1,2,3-triazole, a photocleavable moiety. The aim of the
      present study is to investigate the mechanism of the photorelease by
      characterizing the nanoparticle aggregation status within the cells and
      simulating the electric field enhancement in a range of experimentally realistic
      geometries, such as single Au nanoparticles, dimers, trimers and random
      aggregates. Two plasmon-enhanced processes are examined for triazole
      photocleavage, i.e. three-photon excitation and third-harmonic-generation (one
      photon) excitation. Taking into account the absorption cross sections of the
      triazole, we conclude that the latter mechanism is more efficient, and provides a
      photocleavage rate that explains the experimental findings. Moreover, we
      determine which aggregate geometries are required to maximize the field
      enhancement, and the dependence of such enhancement on the excitation wavelength.
      Our results provide design principles for maximizing the multiphoton molecular
      photorelease by such functionalized gold nanoparticles. 

PMID- 26206492
TI  - Liberating the (data) population from subjugation to the 5% (P-value).

PMID- 26206494
TI  - An Empirical Analysis of Life Jacket Effectiveness in Recreational Boating.
AB  - This article gives a measure of life jacket (LJ) effectiveness in U.S.
      recreational boating. Using the U.S. Coast Guard's Boating Accident Report
      Database from 2008 to 2011, we find that LJ wear is one of the most important
      determinants influencing the number of recreational boating fatalities, together
      with the number of vessels involved, and the type and engine of the vessel(s). We
      estimate a decrease in the number of deceased per vessel of about 80% when the
      operator wears their LJs compared to when they do not. The odds of dying are 86%
      higher than average if the accident involves a canoe or kayak, but 80% lower than
      average when more than one vessel is involved in the accident and 34% lower than
      average when the operator involved in the accident has more than 100 hours of
      boating experience. Interestingly, we find that LJ effectiveness decreases
      significantly as the length of the boat increases and decreases slightly as water
      temperature increases. However, it increases slightly as the operator's age
      increases. We find that between 2008 and 2011, an LJ regulation that requires all
      operators to wear their LJs-representing a 20% increase in wear rate-would have
      saved 1,721 (out of 3,047) boaters or 1,234 out of 2,185 drowning victims. The
      same policy restricted to boats 16-30 feet in length would have saved
      approximately 778 victims. Finally, we find that such a policy would reduce the
      percentage of drowning victims compared to other causes of death. 

PMID- 26206493
TI  - Modulation of schizophrenia-related genes in the forebrain of adolescent and
      adult rats exposed to maternal immune activation.
AB  - Maternal immune activation (MIA) is an environmental risk factor for
      schizophrenia, and may contribute to other developmental disorders including
      autism and epilepsy. Activation of pro-inflammatory cytokine systems by injection
      of the synthetic double-stranded RNA polyriboinosinic-polyribocytidilic acid
      (Poly I:C) mediates important neurochemical and behavioral corollaries of MIA,
      which have relevance to deficits observed in schizophrenia. We examined the
      consequences of MIA on forebrain expression of neuregulin-1 (NRG-1), brain
      derived neurotrophic factor (BDNF) and their receptors, ErbB4 and trkB,
      respectively, genes associated with schizophrenia. On gestational day 14,
      pregnant rats were injected with Poly I:C or vehicle. Utilizing in situ
      hybridization, expression of NRG-1, ErbB4, BDNF, and trkB was examined in male
      rat offspring at postnatal day (P) 14, P30 and P60. ErbB4 mRNA expression was
      significantly increased at P30 in the anterior cingulate (AC Ctx), frontal, and
      parietal cortices, with increases in AC Ctx expression continuing through P60.
      ErbB4 expression was also elevated in the prefrontal cortex (PFC) at P14. In
      contrast, NRG-1 mRNA was decreased in the PFC at P60. Expression of BDNF mRNA was
      significantly upregulated in the PFC at P60 and decreased in the AC Ctx at P14.
      Expression of trkB was increased in two regions, the piriform cortex at P14 and
      the striatum at P60. These findings demonstrate developmentally and regionally
      selective alterations in the expression of schizophrenia-related genes as a
      consequence of MIA. Further study is needed to determine contributions of these
      effects to the development of alterations of relevance to neuropsychiatric
      diseases. 

PMID- 26206496
TI  - Safety and risk assessment of ceramide 3 in cosmetic products.
AB  - Ceramide 3 is used mainly as a moisturizer in various cosmetic products. Although
      several safety studies on formulations containing pseudo-ceramide or ceramide
      have been conducted at the preclinical and clinical levels for regulatory
      approval, no studies have evaluated the systemic toxicity of ceramide 3. To
      address this issue, we conducted a risk assessment and comprehensive
      toxicological review of ceramide and pseudo-ceramide. We assumed that ceramide 3
      is present in various personal and cosmetic products at concentrations of 0.5
      10%. Based on previously reported exposure data, the margin of safety (MOS) was
      calculated for product type, use pattern, and ceramide 3 concentration. Lipsticks
      with up to 10% ceramide 3 (MOS = 4111) are considered safe, while shampoos
      containing 0.5% ceramide 3 (MOS = 148) are known to be safe. Reported MOS values
      for body lotion applied to the hands (1% ceramide 3) and back (5% ceramide 3)
      were 103 and 168, respectively. We anticipate that face cream would be safe up to
      a ceramide 3 concentration of 3% (MOS = 149). Collectively, the MOS approach
      indicated no safety concerns for cosmetic products containing less than 1%
      ceramide 3.

PMID- 26206495
TI  - RIFM fragrance ingredient safety assessment, 2-methyl-3-buten-2-ol, CAS Registry
      Number 115-18-4.
AB  - The use of this material under current use conditions is supported by the
      existing information. This material was evaluated for genotoxicity, repeated dose
      toxicity, developmental toxicity, reproductive toxicity, local respiratory
      toxicity, phototoxicity, skin sensitization potential as well as environmental
      safety. Repeated dose, developmental, and reproductive toxicities were determined
      to have the most conservative systemic exposure derived NO[A]EL of 50 mg/kg/day,
      based on OECD gavage toxicity studies in rats, that resulted in a MOE of 4545455
      after considering 100% absorption from skin contact and inhalation. A MOE of >100
      is deemed acceptable.

PMID- 26206497
TI  - Association between polymorphisms in long non-coding RNA PRNCR1 in 8q24 and risk
      of gastric cancer.
AB  - A long ncRNA (lncRNA) prostate cancer non-coding RNA 1 (PRNCR1) in the 8q24 has
      been reported to be upregulated in prostate cancer with a function of activating
      androgen receptor (AR). AR plays a key role in the gender disparity, cell
      migration, and invasion of gastric cancer (GC). We hypothesized that single
      nucleotide polymorphisms (SNPs) in the lncRNA PRNCR1 may be related to the risk
      of GC. We conducted a case-control study to investigate the association between
      SNPs in the lncRNA PRNCR1 and the risk of GC. Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) assay was used to determine
      the genotypes of 613 subjects including 219 cases with GC and 394 controls. We
      found that patients with the rs13252298AG genotype displayed a 1.50-fold
      increased risk of GC (AG vs. AA, 95 % confidence interval (CI) = 1.05-2.12, p =
      0.02). Interestingly, the rs7007694CT and CC and the rs1456315GG genotypes
      displayed a decreased risk of GC (rs7007694CT vs. TT, odds ratio (OR) = 0.68, 95
      % CI = 0.48-0.97, p = 0.03; rs7007694CC vs. TT, OR = 0.36, 95 % CI = 0.13-0.97, p
      = 0.04; rs1456315GG vs. AA, OR = 0.30, 95 % CI = 0.13-0.70, p = 0.004,
      respectively). Our results suggest that SNPs in the lncRNA PRNCR1 may be a
      biomarker for the etiology of GC. 

PMID- 26206498
TI  - Downregulation of miR-148b as biomarker for early detection of hepatocellular
      carcinoma and may serve as a prognostic marker.
AB  - MicroRNAs (miRNAs) have a large number of various target genes in different
      cancer types, which may result in many biological functions. Thus, identifying
      the molecular mechanisms of miRNAs may effect on the complexity of cancer
      progression via regulation of gene. In the current study, we utilized real-time
      PCR to quantify the diction of miR-148b in trail hepatocellular carcinoma (HCC)
      specimen and normal tissues. Furthermore, we evaluated the relationship of miR
      148b and clinicopathological features with survival of HCC patients. Therefore,
      we evaluated the level of miR-148b expression in 101 HCC patients and also in 40
      normal control cases. The result suggested lower expression in tumor tissues than
      normal control tissues (0.96 +/- 0.14; 1.84 +/- 0.20, P < 0.05). Our findings
      suggest that the declined expression of miR-148b can considerably be linked to
      tumor node metastasis (TNM) stage (stages III and IV; P = 0.021) and vein
      invasion (P = 0.029). Nevertheless, miR-148b expression was not related to sex (P
      = 0.674), age (P = 0. 523), size of tumor (P = 0.507), liver cirrhosis, and
      histologic grade (P = 0.734). Survival analysis showed that low expression was
      remarkably related to overall survival (P = 0.012). Furthermore, multivariate
      survival test suggested that decline of miR-148b diction was linked to poor
      survival in HCC patients. Our results suggested that miR-148b is decreased in
      HCC. Therefore, we concluded that miR-148b may play its role in the prognosis of
      HCC. 

PMID- 26206499
TI  - Complications Following Abdominal-Based Free Flap Breast Reconstruction: Is a 30
      days Complication Rate Representative?
AB  - PURPOSE: The purpose of this study was to analyze timing and frequency of
      complications following free tissue autologous reconstruction in a single
      tertiary care institution. METHODS: From August 2012 to December 2013, all
      patients operated on for abdominal-based free flap breast reconstruction at a
      single institution were included. Complications were identified and risk factors
      associated with them were analyzed using SPSS software. RESULTS: The total number
      of patients was 130 with a total of 191 flaps (69 for unilateral and 61 for
      bilateral reconstructions). Mean surgery time was 570.5 min (+/-151.24). Fifty
      nine of the reconstructed breasts (30.8 %) had early complications. Reoperations
      due to complications were required in 16 (8.3 %) of the breasts during the first
      30 days with seven patients requiring multiple reoperations. Twenty-eight
      patients required reoperations after 30 days, the most frequent reason being
      delayed wound healing and abdominal hernia. The most significant complication was
      a case of disseminated infection with loss of skin coverage of the breasts. Early
      complications and donor-site complications were higher in active smokers (p =
      0.005 and p < 0.001, respectively). Patients with a BMI < 25 had fewer total
      early complications (p = 0.05), as well as fewer complications on the breast area
      (p = 0.02). A longer time in the operating room was associated with an increase
      in late complications (p = 0.018). Bilateral/unilateral operation,
      immediate/delayed surgery, radiotherapy, age, hypertension, diabetes, and surgery
      time were not associated with early complications, late complications, or
      reoperations (p > 0.05). CONCLUSIONS: Active smoking was found to be a
      significant risk factor for early complications, reoperations, and donor-site
      complications. Patients with a normal BMI had fewer early complications,
      reoperations at 30 days, and complications on the breast area. As a significant
      number of complications occurred beyond the standard 30-day reporting period, it
      is important to consider reoperations during an extended period. 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- 26206500
TI  - Objective Comparison of Commercially Available Breast Implant Devices.
AB  - Breast implants are frequently used for both cosmetic breast augmentation and
      breast reconstruction after mastectomy. Three companies currently offer FDA
      approved breast implants (Allergan, Mentor, and Sientra), but their product
      offerings-including permanent breast implants, breast tissue expanders, sizers,
      and post-operative warranty-can be difficult to compare because of brand names
      and company-specific jargon. The ability to have a brand-agnostic understanding
      of all available options is important for both the surgical trainee as well as
      the surgeon in clinical practice. After a brief review of the history of breast
      implant devices, this review utilizes a unique conceptual framework based on
      variables such as fill material, shape, relative dimensions, and surface coating
      to facilitate a better understanding of the similarities and differences between
      the different company's offerings. Specifically, we identify which types of
      devices are offered by all three companies, those that are offered by only one
      company, those that have very limited product offerings, and those combinations
      that are not available at all. Finally, clinical implications are drawn from this
      framework that can be used by both cosmetic and reconstructive surgeons to
      counsel patients about all available options. Importantly, this project is
      entirely independent of any company's funding, support, or input. 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- 26206501
TI  - LC-MS/MS glycomic analyses of free and conjugated forms of the sialic acids,
      Neu5Ac, Neu5Gc and KDN in human throat cancers.
AB  - An elevated level of the free deaminated sialic acid, 2-keto-3-deoxy-D-glycero-D
      galacto-nononic acid (KDN), was first discovered in human ovarian cancers (OCs),
      suggesting that KDN may be an oncodevelopmental antigen (Inoue S, Lin SL, Chang
      T, Wu SH, Yao CW, Chu TY, Troy FA II, Inoue Y. 1998. J Biol Chem. 273(42):27199
      27204). To determine if this unexpected finding was unique to OC, we developed an
      LC-MS/MS glycomic approach to quantitatively determine the level of free and
      conjugated forms of KDN, Neu5Ac and Neu5Gc in head and neck cancers of the
      throat, and in a subpopulation of matched lymph nodes. These findings were
      correlated with tumor (T), nodal (N), metastatic (M) involvement and the
      differentiation status of the tumors. The following new findings are reported:
      (i) The level of free KDN in 49 throat cancers and a subpopulation of 10 regional
      lymph nodes accounted for 94.5 and 93.3%, respectively, of the total level of KDN
      (~2 ug/g); (ii) in marked contrast, the level of free Neu5Ac in throat cancer and
      lymph nodes accounted for only 6.5 and 5.1% of the total level of Neu5Ac (85
      ug/g); (3) The level of Neu5Gc (0.03 ug/g) in throat cancers was 0.30% of the
      level of Neu5Ac, two-thirds were conjugated and one-third was free. The central
      importance of these new findings is that the elevated level of free KDN relative
      to free Neu5Ac and Neu5GC in throat cancers showing no lymphatic metastasis, and
      which are poorly to moderately differentiated, suggests that free KDN may be
      useful as a biomarker for detecting some early-stage cancers at biopsy, and be of
      possible prognostic value in determining the potential degree of malignancy.

PMID- 26206502
TI  - Cytosolic-free oligosaccharides are predominantly generated by the degradation of
      dolichol-linked oligosaccharides in mammalian cells.
AB  - During asparagine (N)-linked protein glycosylation, eukaryotic cells generate
      considerable amounts of free oligosaccharides (fOSs) in the cytosol. It is
      generally assumed that such fOSs are produced by the deglycosylation of misfolded
      N-glycoproteins that are destined for proteasomal degradation or as the result of
      the degradation of dolichol-linked oligosaccharides (DLOs), which serve as glycan
      donor substrates in N-glycosylation reactions. The findings reported herein show
      that the majority of cytosolic fOSs are generated by a peptide:N-glycanase
      (PNGase) and an endo-beta-N-acetylglucosaminidase (ENGase)-independent pathway in
      mammalian cells. The ablation of the cytosolic deglycosylating enzymes, PNGase
      and ENGase, in mouse embryonic fibroblasts had little effect on the amount of
      cytosolic fOSs generated. Quantitative analyses of fOSs using digitonin
      permeabilized cells revealed that they are generated by the degradation of fully
      assembled Glc3Man9GlcNAc2-pyrophosphate-dolichol (PP-Dol) in the lumen of the
      endoplasmic reticulum. Because the degradation of Glc3Man9GlcNAc2-PP-Dol is
      greatly inhibited in the presence of an N-glycosylation acceptor peptide that is
      recognized by the oligosaccharyltransferase (OST), the OST-mediated hydrolysis of
      DLO is the most likely mechanism responsible for the production of a large
      fraction of the cytosolic fOSs. 

PMID- 26206503
TI  - Activity of aminoferrocene-based prodrugs against prostate cancer.
AB  - We tested cytotoxicity of aminoferrocene-based prodrugs towards human androgen
      responsive and unresponsive prostate cancer cell lines LNCaP and DU-145
      correspondingly. Two prodrugs were selected, which are both activated at elevated
      concentrations of ROS with generation of quinone methide (antioxidant system
      inhibitor) and iron-containing compounds (N-benzylaminoferrocene (prodrug 1) and
      Fe salts (2)). We observed that only prodrug 1 is active against the selected
      prostate cancer cells (IC50=11-27 MUM) and its activity correlates with the high
      cell-membrane permeability and increased production of intracellular ROS.

PMID- 26206504
TI  - Identification and optimisation of a 4',5-bisthiazole series of selective
      phosphatidylinositol-3 kinase alpha inhibitors.
AB  - Exploring the affinity-pocket binding moiety of a 2-aminothiazole (S)-proline
      amide-urea series of selective PI3Kalpha inhibitors using a parallel-synthesis
      approach led to the identification of a novel 4',5-bisthiazole sub-series. The
      synthesis and optimisation of both the affinity pocket and (S)-proline amide
      moieties within this 4',5-bisthiazole sub-series are described. From this work a
      number of analogues, including 14 (A66) and 24, were identified as potent and
      selective PI3Kalpha inhibitor in vitro tool compounds. 

PMID- 26206507
TI  - Irido-choroidal coloboma: An atypical presentation?

PMID- 26206505
TI  - Individual differences in response of dorsomedial prefrontal cortex predict daily
      social behavior.
AB  - The capacity to accurately infer the thoughts and intentions of other people is
      critical for effective social interaction, and neural activity in dorsomedial
      prefrontal cortex (dmPFC) has long been linked with the extent to which people
      engage in mental state attribution. In this study, we combined functional
      neuroimaging and experience sampling methodologies to test the predictive value
      of this neural response for daily social behaviors. We found that individuals who
      displayed greater activity in dmPFC when viewing social scenes spent more time
      around other people on a daily basis. These findings suggest a specific role for
      the neural mechanisms that support the capacity to mentalize in guiding
      individuals toward situations containing valuable social outcomes. 

PMID- 26206506
TI  - Comparison of different formulas for intraocular lens power calculation using a
      new optical biometer.
AB  - PURPOSE: To evaluate and compare the predictability of different formulas for
      intraocular lens (IOL) power calculation using a new optical biometer (Aladdin).
      METHODS: This prospective cross-sectional study included 70 eyes of 70 patients
      who underwent uneventful phacoemulsification with IOL implantation. Preoperative
      IOL power calculations were performed using the Aladdin optical biometer.
      Postoperative actual refractive errors and errors predicted by the SRK/T, SRK II,
      Holladay 1, Hoffer Q and Haigis formulas were analyzed. The mean estimation error
      (EE), mean absolute estimation error (AEE) and the percentage of eyes within +/-
      0.50 and +/- 1.00 D of the target refraction for each of five formulas were
      calculated and compared. This analysis was also repeated in three groups formed
      based on axial length (AL) (group 1: <22.5mm, group 2: 22.5-24 mm, group 3: >24
      mm). RESULTS: In the overall study group, the smallest mean AEE was provided by
      the Holladay 1 formula, however there was no statistically significant difference
      in the mean AEE's predicted by the five formulas (P=0.34). The highest percentage
      of eyes within +/- 0.50 and +/- 1.00 D of the target refraction was also found by
      using Holladay 1 (71% and 97%). SRK/T provided smallest mean AEE for groups 1
      (n=13) and 3 (n=16). In group 2 (n=41), the smallest mean AEE was obtained using
      Holladay 1. CONCLUSIONS: Based on the Aladdin biometric data used in our study,
      better results can be obtained using SRK/T formula in eyes with short or long AL.
      The Holladay 1 formula may be preferred in eyes with moderate AL.

PMID- 26206508
TI  - [Femtosecond laser-assisted cataract surgery].
AB  - Femtosecond laser-assisted cataract surgery is a major technological innovation.
      The femtosecond laser, during a pretreatment step, helps to prepare the patient's
      eye for the surgery proper by creating corneal incisions, anterior capsulotomy
      and lens fragmentation in an automated fashion. Thus, these steps can be
      performed with precision and reproducibility, and lens fragmentation reduces the
      amount of ultrasound required during surgery. Drawbacks of this technology are a
      longer operating time, a more demanding surgical procedure and a much higher cost
      for patients and surgical centers. New models of organization in the operating
      room, patient flow, and financial systems have to be designed to adapt this
      procedure to our practice. The benefits of this technology should make it an
      essential tool in the future, provided that cataract surgery can be reconsidered
      logistically and economically. 

PMID- 26206509
TI  - Strain in nonclassical silicon hydrides: An insight into the "ultrastability" of
      sila-bi[6]prismane (Si18 H12) cluster with the endohedrally trapped silicon atom,
      Si19 H12.
AB  - The recently postulated concept of "ultrastability" and "electron-deficient
      aromaticity" (Vach, Nano Lett 2011, 11, 5477; Vach, J Chem Theory Comput 2012, 8,
      2088) in a sila-bi[6]prismane having an additional entrapped silicon atom, Si19
      H12 , has been disproved on the basis of a careful analysis of the energetic
      characteristics related to the formation of this and other silicon hydrides. The
      central silicon atom in Si19 H12 is weaker bound to other silicon atoms than in
      conventional tetrahedral silanes; moreover, Si19 H12 possesses a significant
      amount of strain. The role of strain in the formation of the title compounds has
      been further rationalized by calculating the relative energies for the
      transformation to a half-planar conformation in methane and in silane and by
      calculating the respective strain energies. The strain energy value in Si18 H12
      is equal to 9.93 eV whereas the same property for Si19 H12 lies in range of 6.42
      8.85 eV. Two low-energy isomers of Si19 H12 which lie by 2.77 and 3.42 eV (!)
      lower in energy than the originally considered sila-bi[6]prismane-based structure
      have been proposed.

PMID- 26206511
TI  - Complementarity and congruence between exact NOEs and traditional NMR probes for
      spatial decoding of protein dynamics.
AB  - The study of the spatial sampling of biomolecules is essential to understanding
      the structure-dynamics-function relationship. We have established a protocol for
      the determination of multiple-state ensembles based on exact measurements of the
      nuclear Overhauser effect (eNOE). The protocol is practical since it does not
      require any additional data, while all other NMR data sets must be supplemented
      by NOE restraints. The question arises as to how much structural and dynamics
      information is shared between the eNOEs and other NMR probes. We compile one of
      the largest and most diverse NMR data sets of a protein to date consisting of
      eNOEs, RDCs and J couplings for GB3. We show that the eNOEs improve the back
      prediction of RDCs and J couplings, either upon use of more than one state, or in
      comparison to conventional NOEs. Our findings indicate that the eNOE data is self
      consistent, consistent with other data, and that the structural representation
      with multiple states is warranted. 

PMID- 26206510
TI  - Novel Small Molecule Entry Inhibitors of Ebola Virus.
AB  - BACKGROUND: The current Ebola virus (EBOV) outbreak has highlighted the troubling
      absence of available antivirals or vaccines to treat infected patients and stop
      the spread of EBOV. The EBOV glycoprotein (GP) plays critical roles in the early
      stage of virus infection, including receptor binding and membrane fusion, making
      it a potential target for the development of anti-EBOV drugs. We report the
      identification of 2 novel EBOV inhibitors targeting viral entry. METHODS: To
      identify small molecule inhibitors of EBOV entry, we carried out a cell-based
      high-throughput screening using human immunodeficiency virus-based pseudotyped
      viruses expressing EBOV-GP. Two compounds were identified, and mechanism-of
      action studies were performed using immunoflourescence, AlphaLISA, and enzymatic
      assays for cathepsin B inhibition. RESULTS: We report the identification of 2
      novel entry inhibitors. These inhibitors (1) inhibit EBOV infection (50%
      inhibitory concentration, approximately 0.28 and approximately 10 umol/L) at a
      late stage of entry, (2) induce Niemann-Pick C phenotype, and (3) inhibit GP
      Niemann-Pick C1 (NPC1) protein interaction. CONCLUSIONS: We have identified 2
      novel EBOV inhibitors, MBX2254 and MBX2270, that can serve as starting points for
      the development of an anti-EBOV therapeutic agent. Our findings also highlight
      the importance of NPC1-GP interaction in EBOV entry and the attractiveness of
      NPC1 as an antifiloviral therapeutic target.

PMID- 26206512
TI  - Serum 25-hydroxy vitamin D level in patients with pemphigus and its association
      with disease severity.
AB  - BACKGROUND: There is a growing number of studies suggesting a key role for
      vitamin D in the pathogenesis and progression of autoimmune disorders. AIM: To
      determine the serum levels of 25-hydroxy vitamin D [25(OH)D] in patients with
      pemphigus and association of 25(OH)D with clinical features. METHODS: We enrolled
      52 patients with pemphigus and 56 age- and sex-matched healthy controls (HCs).
      Only patients newly diagnosed with pemphigus or patients who had relapsed after
      discontinuing their treatment for > 6 months were included. Serum 25(OH)D and
      parathyroid hormone (PTH) levels were measured. Data on demographics, body mass
      index (BMI), disease severity (based on Pemphigus Area and Activity Score; PAAS)
      and involved surface body area (BSA) were obtained. RESULTS: Suboptimal levels of
      vitamin D (< 30 ng/mL) were observed in 78.8% and 91.0% of patients and HCs,
      respectively (P = 0.13). Univariate and multivariate ordinal logistic regression
      models showed that low vitamin D status was more likely to occur in patients with
      higher BSA (OR = 1.07, 95% CI 1.01-1.13) and those with higher cutaneous (OR =
      1.36, 95% CI 1.11-1.66) and total (OR = 1.24, 95% CI 1.08-1.41) PAAS. However,
      there was no significant association between vitamin D levels and presence of
      pemphigus, season of sampling, age, BMI or smoking habit. CONCLUSION: Vitamin D
      deficiency is common both in patients with pemphigus and in HCs. Patients with
      more severe disease (higher PAAS) are likely to have lower vitamin D levels.

PMID- 26206513
TI  - Technical characteristics of current cardiotocographic monitors.
AB  - Cardiotocographic (CTG) monitors are complex electronic devices developed to
      acquire, process and display foetal heart rate (FHR) and uterine contraction (UC)
      signals. This chapter describes the main characteristics of current CTG monitors,
      in order to allow a better understanding of the technology. An ultrasound
      transducer is used for the external monitoring of FHR signals, whereas a
      tocodynamometer is used for the external monitoring of UCs. These technologies
      are recommended for routine clinical use in both the antepartum and intrapartum
      periods. Foetal electrode and intrauterine pressure sensors provide internal
      monitoring of FHR and UC signals, respectively, which are more precise than
      external signals. They are only applicable during labour, after cervical
      dilatation and ruptured membranes, and they have established contraindications.
      The registration of foetal movements, simultaneous monitoring of twins and
      triplets, continuous maternal heart rate monitoring, monitoring of other maternal
      parameters, alarms, digital outputs and telemetry are other available
      characteristics in some CTG monitors. 

PMID- 26206514
TI  - Combined cardiotocographic and ST event analysis: A review.
AB  - ST-analysis of the fetal electrocardiogram (ECG) (STAN((r))) combined with
      cardiotocography (CTG) for intrapartum fetal monitoring has been developed
      following many years of animal research. Changes in the ST-segment of the fetal
      ECG correlated with fetal hypoxia occurring during labor. In 1993 the first
      randomized controlled trial (RCT), comparing CTG with CTG + ST-analysis was
      published. STAN((r)) was introduced for daily practice in 2000. To date, six RCTs
      have been performed, out of which five have been published. Furthermore, there
      are six published meta-analyses. The meta-analyses showed that CTG + ST-analysis
      reduced the risks of vaginal operative delivery by about 10% and fetal blood
      sampling by 40%. There are conflicting results regarding the effect on metabolic
      acidosis, much because of controveries about which RCTs should be included in a
      meta-analysis, and because of differences in methodology, execution and quality
      of the meta-analyses. Several cohort studies have been published, some showing
      significant decrease of metabolic acidosis after the introduction of ST-analysis.
      In this review, we discuss not only the scientific evidence from the RCTs and
      meta-analyses, but also the limitations of these studies. In conclusion, ST
      analysis is effective in reducing operative vaginal deliveries and fetal blood
      sampling but the effect on neonatal metabolic acidosis is still under debate.
      Further research is needed to determine the place of ST-analysis in the labor
      ward for daily practice. 

PMID- 26206515
TI  - Clinical outcome of image-guided adaptive radiotherapy in the treatment of lung
      cancer patients.
AB  - BACKGROUND: Adaptive strategy with daily online tumour match is a treatment
      option when treating locally advanced lung cancer patients with curative intended
      radiotherapy (RT). MATERIAL AND METHODS: Fifty-two consecutive lung cancer
      patients treated with soft tissue match, adaptive RT and small planning target
      volumes (PTV) margins were analysed. A control group of 52 consecutive patients
      treated with bone match, no adaptive strategy and larger margins was included.
      Patients were followed with computed tomography (CT) scans every third month. CT
      images showing loco-regional recurrences were identified. The recurrence gross
      tumour volume was delineated and registered with the original radiation treatment
      plan to identify site of failure. All patients were toxicity-scored using CTCAE
      4.03 grading scale. Data were analysed using the Kaplan-Meier analysis. RESULTS:
      The median follow-up time was 16 months (3-35). Within a year, 35% of the
      patients in the adaptive group (ART-group) and 53% in the control group (No-ART
      group) experienced loco-regional failure, showing improved loco-regional control
      in the ART group (p = 0.05). One patient in the ART-group and four patients in
      the No-ART-group showed marginal failure. Median overall progression-free
      survival time for the ART-group was 10 months (95% CI 8-12), and 8 months (95% CI
      6-9) for the No-ART-group. Severe pneumonitis (grade 3-5) decreased from 22% in
      the No-ART-group to 18% in the ART-group (non-significant, p = 0.6). No
      significant difference in severe dysphagia was found between the two groups.
      CONCLUSION: In the first small cohort of patients investigated, implementation of
      soft-tissue tumour match and adaptive strategies for locally advanced lung cancer
      patients increased the loco-regional control rate without increasing treatment
      related toxicity.

PMID- 26206516
TI  - Quality assurance of radiation therapy for head and neck cancer patients treated
      in DAHANCA 10 randomized trial.

PMID- 26206517
TI  - Comparison of onboard low-field magnetic resonance imaging versus onboard
      computed tomography for anatomy visualization in radiotherapy.
AB  - BACKGROUND: Onboard magnetic resonance imaging (OB-MRI) for daily localization
      and adaptive radiotherapy has been under development by several groups. However,
      no clinical studies have evaluated whether OB-MRI improves visualization of the
      target and organs at risk (OARs) compared to standard onboard computed tomography
      (OB-CT). This study compared visualization of patient anatomy on images acquired
      on the MRI-(60)Co ViewRay system to those acquired with OB-CT. MATERIAL AND
      METHODS: Fourteen patients enrolled on a protocol approved by the Institutional
      Review Board (IRB) and undergoing image-guided radiotherapy for cancer in the
      thorax (n = 2), pelvis (n = 6), abdomen (n = 3) or head and neck (n = 3) were
      imaged with OB-MRI and OB-CT. For each of the 14 patients, the OB-MRI and OB-CT
      datasets were displayed side-by-side and independently reviewed by three
      radiation oncologists. Each physician was asked to evaluate which dataset offered
      better visualization of the target and OARs. A quantitative contouring study was
      performed on two abdominal patients to assess if OB-MRI could offer improved
      inter-observer segmentation agreement for adaptive planning. RESULTS: In total
      221 OARs and 10 targets were compared for visualization on OB-MRI and OB-CT by
      each of the three physicians. The majority of physicians (two or more) evaluated
      visualization on MRI as better for 71% of structures, worse for 10% of
      structures, and equivalent for 14% of structures. 5% of structures were not
      visible on either. Physicians agreed unanimously for 74% and in majority for >
      99% of structures. Targets were better visualized on MRI in 4/10 cases, and never
      on OB-CT. CONCLUSION: Low-field MR provides better anatomic visualization of many
      radiotherapy targets and most OARs as compared to OB-CT. Further studies with OB
      MRI should be pursued.

PMID- 26206518
TI  - Adaptation requirements due to anatomical changes in free-breathing and deep
      inspiration breath-hold for standard and dose-escalated radiotherapy of lung
      cancer patients.
AB  - BACKGROUND: Radiotherapy of lung cancer patients is subject to uncertainties
      related to heterogeneities, anatomical changes and breathing motion. Use of deep
      inspiration breath-hold (DIBH) can reduce the treated volume, potentially
      enabling dose-escalated (DE) treatments. This study was designed to investigate
      the need for adaptation due to anatomical changes, for both standard (ST) and DE
      plans in free-breathing (FB) and DIBH. MATERIAL AND METHODS: The effect of tumor
      shrinkage (TS), pleural effusion (PE) and atelectasis was investigated for
      patients and for a CIRS thorax phantom. Sixteen patients were computed tomography
      (CT) imaged both in FB and DIBH. Anatomical changes were simulated by CT
      information editing and re-calculations, of both ST and DE plans, in the
      treatment planning system. PE was systematically simulated by adding fluid in the
      dorsal region of the lung and TS by reduction of the tumor volume. RESULTS:
      Phantom simulations resulted in maximum deviations in mean dose to the GTV-T
      (<D>GTV-T) of -1% for 3 cm PE and centrally located tumor, and + 3% for TS from 5
      cm to 1 cm diameter for an anterior tumor location. For the majority of the
      patients, simulated PE resulted in a decreasing <D>GTV-T with increasing amount
      of fluid and increasing <D>GTV-T for decreasing tumor volume. Maximum change in
      <D>GTV-T of -3% (3 cm PE in FB for both ST and DE plans) and + 10% (2 cm TS in FB
      for DE plan) was observed. Large atelectasis reduction increased the <D>GTV-T
      with 2% for FB and had no effect for DIBH. CONCLUSION: Phantom simulations
      provided potential adaptation action levels for PE and TS. For the more complex
      patient geometry, individual assessment of the dosimetric impact is recommended
      for both ST and DE plans in DIBH as well as in FB. However, DIBH was found to be
      superior over FB for DE plans, regarding robustness of <D>GTV-T to TS.

PMID- 26206519
TI  - Delineating the inner bladder surface using uniform contractions from the outer
      surface under variable bladder filling conditions.
AB  - OBJECTIVE: To evaluate the methods to delineate the inner bladder (IB) surface
      using a uniform contraction from the outer bladder (OB) surface, assuming the
      bladder wall (BW) is either of constant thickness, constant volume or variable
      volume. METHODS: 14 prostate intensity-modulated radiotherapy patients with 2
      planning CTs were identified. For both CTs, OB was delineated using model-based
      segmentation. IB was delineated manually. Then, using uniform contractions from
      OB, the position of IB was approximated using a: 2.5-mm contraction, patient
      specific contraction, patient-specific constant wall volume method and variable
      wall volume method. The structures created using those strategies were compared
      against the manual IB contours using geometric and dosimetric indices. RESULTS:
      In the presence of variable bladder filling, use of a generic or patient-specific
      constant contraction resulted in a significant overestimation of IB volume (+12
      and +13 cm(3), respectively; p < 0.001) that was inversely correlated with the
      difference in urine volume between the scans (R(2) > 0.86). Mean differences
      across 95% of IB surfaces were <=2 mm for methods using either constant or
      variable wall volume. Mean dose-volume histogram (DVH) differences were <1 cm(3)
      across the whole BW DVH when using the method that assumed a variable wall
      volume. CONCLUSION: The variable volume BW model provided the best approximation
      of the IB surface position under varying filling conditions, based on geometric
      and dosimetric indices. ADVANCES IN KNOWLEDGE: Use of the equation derived in
      this research provides a quick and accurate method to delineate the hollow BW on
      serial imaging for the purposes of dose reconstruction.

PMID- 26206520
TI  - Psoriasiform cutaneous sporotrichosis.

PMID- 26206522
TI  - Proton uptake in the H(+)-SOFC cathode material Ba(0.5)Sr(0.5)Fe(0.8)Zn(0.2)O(3
      delta): transition from hydration to hydrogenation with increasing oxygen partial
      pressure.
AB  - Thermogravimetric investigations on the perovskite
      Ba(0.5)Sr(0.5)Fe(0.8)Zn(0.2)O(3-delta) (BSFZ, with mixed hole, oxygen vacancy and
      proton conductivity) from water vapor can occur by acid-base reaction (hydration)
      or redox reaction (hydrogen uptake), depending on the oxygen partial pressure,
      i.e. on the material's defect concentrations. In parallel, the effective
      diffusion coefficient of the stoichiometry relaxation kinetics also changes.
      These striking observations can be rationalized in terms of a defect chemical
      model and transport equations for materials with three mobile carriers.
      Implications for the search of cathode materials with mixed electronic and
      protonic conductivity for application on proton conducting oxide electrolytes are
      discussed.

PMID- 26206521
TI  - Spatiotemporal dynamics of Aurora B-PLK1-MCAK signaling axis orchestrates
      kinetochore bi-orientation and faithful chromosome segregation.
AB  - Chromosome segregation in mitosis is orchestrated by the dynamic interactions
      between the kinetochore and spindle microtubules. The microtubule depolymerase
      mitotic centromere-associated kinesin (MCAK) is a key regulator for an accurate
      kinetochore-microtubule attachment. However, the regulatory mechanism underlying
      precise MCAK depolymerase activity control during mitosis remains elusive. Here,
      we describe a novel pathway involving an Aurora B-PLK1 axis for regulation of
      MCAK activity in mitosis. Aurora B phosphorylates PLK1 on Thr210 to activate its
      kinase activity at the kinetochores during mitosis. Aurora B-orchestrated PLK1
      kinase activity was examined in real-time mitosis using a fluorescence resonance
      energy transfer-based reporter and quantitative analysis of native PLK1 substrate
      phosphorylation. Active PLK1, in turn, phosphorylates MCAK at Ser715 which
      promotes its microtubule depolymerase activity essential for faithful chromosome
      segregation. Importantly, inhibition of PLK1 kinase activity or expression of a
      non-phosphorylatable MCAK mutant prevents correct kinetochore-microtubule
      attachment, resulting in abnormal anaphase with chromosome bridges. We reason
      that the Aurora B-PLK1 signaling at the kinetochore orchestrates MCAK activity,
      which is essential for timely correction of aberrant kinetochore attachment to
      ensure accurate chromosome segregation during mitosis. 

PMID- 26206523
TI  - Role of organic cation transporters in drug-drug interaction.
AB  - INTRODUCTION: Organic cation transporters OCT1, OCT2 and OCT3 expressed in the
      small intestine, liver, brain and other organs play important roles in
      absorption, excretion and distribution of cationic drugs. Drug-drug interactions
      at OCTs may change pharmacokinetics, pharmacodynamics and drug toxicity.
      Knowledge about physiological and biomedical functions of OCTs and the molecular
      mechanisms of transport and inhibition is required to anticipate drug-drug
      interactions and their potential biomedical impact. AREAS COVERED: Current
      knowledge about structure, polyspecific cation binding and transport of OCTs is
      summarized. Tissue distributions of OCT1-3 and their presumed physiological roles
      in the small intestine, liver, kidney and brain are reported, and drugs that are
      transported by human OCT1-3 are listed. The impact of human OCTs for
      pharmacokinetics and pharmacodynamics of the antidiabetic metformin and
      antineoplastic platinum derivatives are discussed. In addition, interactions of
      drugs that are transported by OCTs observed in the kidney and liver are reported.
      Procedures to test novel drugs for drug-drug interactions at OCTs in vitro and in
      clinical studies are recommended. EXPERT OPINION: When performing in vitro
      testing for drug-drug interactions, it must be considered that one inhibitory
      drug may inhibit different transported drugs with different affinities. After
      positive in vitro testing for drug-drug interaction, clinical tests are
      obligatory.

PMID- 26206525
TI  - Quantitative Comparison of 2 Dual-Energy X-ray Absorptiometry Systems in
      Assessing Body Composition and Bone Mineral Measurements.
AB  - Dual-energy X-ray absorptiometry (DXA) is widely used in body composition
      measurement and evaluation. Because of its numerous applications, the probability
      of instrument discrepancies has increased dramatically. This study quantitatively
      compares 2 different DXA systems. In this study, 96 subjects (60 female and 36
      male, aged 19-82 years) were recruited and scanned using a General Electric Lunar
      iDXA and a Hologic Discovery scanner. Four measurements (percent fat, total mass,
      bone mineral density [BMD], and bone mineral content [BMC]) were quantitatively
      compared in the whole body and in specific anatomic regions (arms, legs, trunk,
      android, gynoid, head, ribs, and pelvis). A simple linear regression of each
      measurement was performed to examine the correlation between the 2 systems.
      Percent fat, total mass, BMC, and BMD were highly correlated between the 2 DXA
      systems, with correlation r values greater than 0.854 for both the whole body and
      the individual anatomic regions except for BMC and BMD in ribs. The high
      correlation between the 2 DXA systems with systematic differences enabled
      development of calibration equations for extending the multisystem measurements
      to advanced quantitative analyses.

PMID- 26206524
TI  - Contrast-enhanced ultrasound: clinical applications in patients with
      atherosclerosis.
AB  - Contrast-enhanced ultrasound (CEUS) is increasingly being used to evaluate
      patients with known or suspected atherosclerosis. The administration of a
      microbubble contrast agent in conjunction with ultrasound results in an improved
      image quality and provides information that cannot be assessed with standard B
      mode ultrasound. CEUS is a high-resolution, noninvasive imaging modality, which
      is safe and may benefit patients with coronary, carotid, or aortic
      atherosclerosis. CEUS allows a reliable assessment of endocardial borders, left
      ventricular function, intracardiac thrombus and myocardial perfusion. CEUS
      results in an improved detection of carotid atherosclerosis, and allows
      assessment of high-risk plaque characteristics including intraplaque
      vascularization, and ulceration. CEUS provides real-time bedside information in
      patients with a suspected or known abdominal aortic aneurysm or aortic
      dissection. The absence of ionizing radiation and safety of the contrast agent
      allow repetitive imaging which is particularly useful in the follow-up of
      patients after endovascular aneurysm repair. New developments in CEUS-based
      molecular imaging will improve the understanding of the pathophysiology of
      atherosclerosis and may in the future allow to image and directly treat
      cardiovascular diseases (theragnostic CEUS). Familiarity with the strengths and
      limitations of CEUS may have a major impact on the management of patients with
      atherosclerosis. 

PMID- 26206526
TI  - Prediction of Areal Bone Mineral Density and Bone Mineral Content in Children and
      Adolescents Living With HIV Based on Anthropometric Variables.
AB  - Children and adolescents living with HIV have low bone mass for age. There are
      reliable and accurate methods for evaluation of bone mass, however, alternative
      methods are necessary, especially, for application in limited-resource scenarios.
      Anthropometry is a noninvasive and low cost method that can predict bone mass in
      healthy youths. The aim of the study was to develop predictive equations for bone
      mineral content and bone mineral density in children and adolescents living with
      HIV based on anthropometric variables. Forty-eight children and adolescents of
      both sexes (24 females) from 7 to 17 years, living in greater Florianopolis area,
      Santa Catarina, Brazil, who were under clinical follow-up at "Hospital Infantil
      Joana de Gusmao", participated in the study. Dual-energy X-ray absorptiometry was
      used to evaluate whole-body bone mineral content (BMC) and areal bone mineral
      density (aBMD). Height, body weight, bone diameters, arm circumference, and
      triceps skinfold were measured and the body mass index and arm muscle area were
      calculated. Multiple regression models were fitted to predict BMC and aBMD, using
      backward selection (p >= 0.05). Two predictive models with high R2 values (84%
      94%) were developed. Model 1 to estimate aBMD [Y = -0.1450124 + (height *
      0.0033807) + (age * 0.0146381) + (body mass index * 0.0158838) + (skin color *
      0.0421068)], and model 2 to estimate BMC [Y = 1095.1 + (body weight * 45.66973) +
      (age * 31.36516) + (arm circumference * -53.27204) + (femoral diameter * 
      9.594018)].The predictive models using anthropometry provided reliable estimates
      and can be useful to monitor aBMD and BMC in children and adolescents living with
      human immunodeficiency virus where limited resources are available.

PMID- 26206527
TI  - Ultrasonic wave based pressure measurement in small diameter pipeline.
AB  - An effective non-intrusive method of ultrasound-based technique that allows
      monitoring liquid pressure in small diameter pipeline (less than 10mm) is
      presented in this paper. Ultrasonic wave could penetrate medium, through the
      acquisition of representative information from the echoes, properties of medium
      can be reflected. This pressure measurement is difficult due to that echoes'
      information is not easy to obtain in small diameter pipeline. The proposed method
      is a study on pipeline with Kneser liquid and is based on the principle that the
      transmission speed of ultrasonic wave in pipeline liquid correlates with liquid
      pressure and transmission speed of ultrasonic wave in pipeline liquid is
      reflected through ultrasonic propagation time providing that acoustic distance is
      fixed. Therefore, variation of ultrasonic propagation time can reflect variation
      of pressure in pipeline. Ultrasonic propagation time is obtained by electric
      processing approach and is accurately measured to nanosecond through high
      resolution time measurement module. We used ultrasonic propagation time
      difference to reflect actual pressure in this paper to reduce the environmental
      influences. The corresponding pressure values are finally obtained by acquiring
      the relationship between variation of ultrasonic propagation time difference and
      pressure with the use of neural network analysis method, the results show that
      this method is accurate and can be used in practice. 

PMID- 26206528
TI  - Effect of laser suture lysis on filtration openings: a prospective three
      dimensional anterior segment optical coherence tomography study.
AB  - PURPOSE: To investigate the effects of laser suture lysis (LSL) on filtration
      openings after trabeculectomy. METHODS: Prospective study analyzing the changes
      in the location and width of filtration openings, fluid cavity height, total bleb
      height, bleb wall thickness, and bleb wall intensity before and after LSL using
      three-dimensional anterior segment optical coherence tomography (3D AS-OCT).
      RESULTS: Fourteen patients had clear scleral flap image analysis. As five
      patients underwent LSL twice and two patients underwent LSL thrice, 23 comparison
      studies were possible. After LSL the intraocular pressure (IOP) decreased (P =
      0.0015) from 20.5 +/- 5.3 to 14.9 +/- 6.4 mm Hg, and the fluid cavity height
      increased significantly from 0.2 +/- 0.2 mm to 0.3 +/- 0.1 mm (P = 0.0094). Other
      bleb parameters were not significantly different when comparing before and after
      LSL. When the IOP reduction ratio was > 25% following LSL, the width of the
      filtration openings on the LSL side, the total bleb height, and the fluid cavity
      height increased (P = 0.0273, 0.0342, and 0.0024, respectively). In multiple
      regression analysis the changes in fluid cavity height, the wall thickness, the
      wall intensity, and the width of the filtration opening were positively
      associated with the IOP reduction rate (P = 0.0428, 0.0226, 0.0420, and 0.0356,
      respectively). CONCLUSIONS: 3D AS-OCT allowed a detailed examination of the
      internal morphology of filtration blebs and openings before and after LSL. The
      changes in the internal morphology were closely associated with the success of
      LSL to decrease IOP.

PMID- 26206530
TI  - Evaluating the impact of summer vacation on the visual acuity of AMD patients
      treated with ranibizumab.
AB  - PURPOSE: To evaluate the impact of traditional French summer vacation on visual
      acuity and spectral domain-optical coherence tomography (SD-OCT) of Wet AMD
      patients being treated with intravitreal Ranibizumab. METHODS: This was a
      consecutive, comparative, single-centre, prospective analysis. All patients who
      were being treated with intravitreal injection of 0.5 mg ranibizumab at Cergy
      Pontoise Hospital, Department of Ophthalmology between July 2013 and September
      2014 were included. Patients were divided into two groups: (A) patients who
      skipped one ranibizumab intravitreal injection during holidays, and (B) patients
      who received injection during their holidays. Evaluations occurred prior to
      traditional holiday (baseline) and 2 months later, consisting of BCVA using
      ETDRS, and a complete ophthalmic examination that included slit-lamp
      biomicroscopy, fundus examination, fluorescein angiography (FA), indocyanine
      green angiography (ICGA), and spectral domain-optical coherence tomography (SD
      OCT). All patients were being treated with PRN anti-VEGF regimen and criteria for
      reinjection included a visual acuity loss >5 ETDRS letters and/or an increase of
      central retinal thickness, presence of subretinal fluid, intraretinal fluid, or
      pigment epithelium detachment. If reinjection criteria were not met, patients
      were advised to return in 4 weeks. RESULTS: The mean visual acuity change was 
      0.071 +/- 0.149 (LogMAR) in group A and + 0.003 +/- 0.178 in group B (P = 0.041).
      At the second visit (2 months after preholidays visit), 61.8% of patients in
      group A had SRF and/or intraretinal cysts, and only 27.6% of patients in group B.
      There was a significant difference in the persistence of fluid between the two
      groups (P = 0.007, chi(2)-test). CONCLUSION: This cases series demonstrated the
      detrimental impact of holidays on visual acuity in patients treated with
      ranibizumab for AMD, which, in spite of their treatment regimen, still leave in
      vacation. Therefore, it is important to convey the message of treatment adherence
      to patients, despite their need of holidays.

PMID- 26206529
TI  - The genetic mechanisms of primary angle closure glaucoma.
AB  - Primary Angle Closure Glaucoma (PACG) is one of the most common types of glaucoma
      affecting over 15 million individuals worldwide. Family history and ethnicity are
      strongly associated with the development of the disease, suggesting that one or
      more genetic factors contribute to PACG. Although strictly heritable disease
      causing mutations have not been identified, a number of recent association
      studies have pointed out genetic factors that appear to contribute to an
      individual's risk to develop PACG. In addition, genetic factors have been
      identified that modify PACG endophenotypes for example, axial length. Herein we
      review the current literature on this important topic. 

PMID- 26206531
TI  - Effectiveness of a smartphone application for testing near visual acuity.
AB  - PURPOSE: The purpose of this study was to evaluate the discrepancy between the
      near visual acuity (VA) measurements using the EyeHandBook smartphone application
      and the conventional method of using the near vision card. METHODS: Using similar
      environmental/examinational conditions, near VA measurements were obtained and
      compared using the near vision card and the EyeHandBook app for IPhone 5 from 100
      subjects. The obtained data were changed to LogMAR format and the relationship
      between the two techniques was analyzed by paired sample t-test and scatterplot.
      RESULTS: With a P-value of<0.0001, our results indicate that the EyeHandBook
      application running on IPhone 5 overestimates the near VA compared with the
      conventional near vision card by an average of 0.11 LogMAR unless the measurement
      done by the near vision card was 20/20. CONCLUSIONS: Owing to vast utilization of
      portable high-definition screens in VA measurements, eye-care providers have to
      be mindful of the potential disparity in VA measurement between different
      platforms, which in our study was likely secondary to the high contrast and
      brightness levels of the smartphone's high-definition screen when compared with
      the near vision card.

PMID- 26206532
TI  - Design characteristic of randomised controlled trials for geographic atrophy in
      age-related macular degeneration: selection of outcomes and sample size
      calculation.
AB  - PURPOSE: The selection of suitable outcomes and sample size calculation are
      critical factors in the design of a randomised controlled trial (RCT). The goal
      of this study was to identify the range of outcomes and information on sample
      size calculation in RCTs on geographic atrophy (GA). METHODS: We carried out a
      systematic review of age-related macular degeneration (AMD) RCTs. We searched
      MEDLINE, EMBASE, Scopus, Cochrane Library, www.controlled-trials.com, and
      www.ClinicalTrials.gov. Two independent reviewers screened records. One reviewer
      collected data and the second reviewer appraised 10% of collected data. We
      scanned references lists of selected papers to include other relevant RCTs.
      RESULTS: Literature and registry search identified 3816 abstracts of journal
      articles and 493 records from trial registries. From a total of 177 RCTs on all
      types of AMD, 23 RCTs on GA were included. Eighty-one clinical outcomes were
      identified. Visual acuity (VA) was the most frequently used outcome, presented in
      18 out of 23 RCTs and followed by the measures of lesion area. For sample size
      analysis, 8 GA RCTs were included. None of them provided sufficient Information
      on sample size calculations. CONCLUSIONS: This systematic review illustrates a
      lack of standardisation in terms of outcome reporting in GA trials and issues
      regarding sample size calculation. These limitations significantly hamper
      attempts to compare outcomes across studies and also perform meta-analyses.

PMID- 26206534
TI  - Re: inter-rater reliability and validity of the Ministry of Health of Turkey's
      mandatory emergency triage instrument.

PMID- 26206533
TI  - CyclinD1 Down-Regulation and Increased Apoptosis Are Common Features of
      Cohesinopathies.
AB  - Genetic variants within components of the cohesin complex (NIPBL, SMC1A, SMC3,
      RAD21, PDS5, ESCO2, HDAC8) are believed to be responsible for a spectrum of human
      syndromes known as "cohesinopathies" that includes Cornelia de Lange Syndrome
      (CdLS). CdLS is a multiple malformation syndrome affecting almost any organ and
      causing severe developmental delay. Cohesinopathies seem to be caused by
      dysregulation of specific developmental pathways downstream of mutations in
      cohesin components. However, it is still unclear how mutations in different
      components of the cohesin complex affect the output of gene regulation. In this
      study, zebrafish embryos and SMC1A-mutated patient-derived fibroblasts were used
      to analyze abnormalities induced by SMC1A loss of function. We show that the
      knockdown of smc1a in zebrafish impairs neural development, increases apoptosis,
      and specifically down-regulates Ccnd1 levels. The same down-regulation of cohesin
      targets is observed in SMC1A-mutated patient fibroblasts. Previously, we have
      demonstrated that haploinsufficiency of NIPBL produces similar effects in
      zebrafish and in patients fibroblasts indicating a possible common feature for
      neurological defects and mental retardation in cohesinopathies. Interestingly,
      expression analysis of Smc1a and Nipbl in developing mouse embryos reveals a
      specific pattern in the hindbrain, suggesting a role for cohesins in neural
      development in vertebrates.

PMID- 26206535
TI  - Cerebral small vessel disease is related to disturbed 24-h activity rhythms: a
      population-based study.
AB  - BACKGROUND AND PURPOSE: Cerebral small vessel disease is common in elderly
      persons. Patients with dementia or stroke frequently have cerebral small vessel
      disease and often experience disturbances in the sleep-wake rhythm. It is unknown
      whether cerebral small vessel disease is related to disturbances in sleep and 24
      h activity rhythms. METHODS: This study was conducted in the Rotterdam Study. A
      total of 970 community-dwelling persons (mean age 59.2 years) underwent brain
      magnetic resonance imaging and actigraphy. Cerebral small vessel disease was
      defined as white matter lesions (total volume in millilitres) and the presence of
      cerebral microbleeds and lacunar infarcts. Twenty-four hour activity rhythms and
      sleep were measured with actigraphy by estimating the instability and
      fragmentation of the activity rhythm and total sleep time. Sleep quality was
      assessed with the Pittsburgh Sleep Quality Index. White matter lesions,
      instability, fragmentation and sleep quality were standardized for analyses.
      RESULTS: Higher white matter lesion volume (B = 0.09 per SD, 95% confidence
      interval 0.02; 0.15) and cerebral microbleeds (B = 0.19 per SD, 95% confidence
      interval 0.02; 0.37) were significantly related to more fragmented 24-h activity
      rhythms. None of the small vessel disease markers was related to total sleep time
      or sleep quality. CONCLUSIONS: White matter lesion volume and the presence of
      cerebral microbleeds are related to disturbed activity rhythms. This suggests
      that subclinical brain damage affects the 24-h activity rhythm.

PMID- 26206537
TI  - A 17-Year-Old Female Patient With a Lithium Overdose.

PMID- 26206538
TI  - Targeted Temperature Management: Part 2.

PMID- 26206540
TI  - Articles That May Change Your Practice: Tranexamic Acid.

PMID- 26206539
TI  - Finding What You're Looking For.

PMID- 26206541
TI  - Statistics Say the Industry Is Safer.

PMID- 26206542
TI  - Critical Care Transport Training: New Strides in Simulating the Austere
      Environment.
AB  - The air medical transport arena requires the practitioner to develop clinical and
      diagnostic reasoning abilities to manage the dynamic needs of the patient in
      unstructured, uncertain, and often unforgiving environments. High-fidelity
      simulation can be instrumental in training interprofessional flight teams to
      improve competency through quality and safe patient care during medical transport
      that may otherwise take years to learn because of the inconsistency in real-world
      experiences. Because of the suboptimal circumstantial conditions inherent to
      critical care transport, a helicopter simulator designed to discretely replicate
      the phases of flight and train teams in air medical transport scenarios has been
      developed at the Dorothy Ebersbach Academic Center for Flight Nursing at the
      Frances Payne Bolton School of Nursing in Cleveland, OH. The goal is to prepare
      interdisciplinary critical care transport flight teams in collaborative practice,
      research, and leadership through measurable and highly structured learning
      activities. 

PMID- 26206543
TI  - Should Charity Air Medical Organizations Require Commercial Certification of
      Their Pilots?
AB  - OBJECTIVE: Fixed wing medical transportation crashes operating under 14 CFR Part
      91 show higher fatal outcomes than nonmedical Part 91 flights. Advanced
      certification may translate into increased safety, yet we know of no charity air
      medical transportation requiring such certification. Herein, in a retrospective
      study, we determined whether commercial certification is associated with a
      reduced fatality rate compared with the less stringent private pilot certificate
      and accident causes. METHODS: The National Transportation Safety Board accident
      database was queried for fatal accidents in single-engine aircraft occurring
      between 2002 and 2012. Poisson and proportion tests were used in statistical
      analyses. RESULTS: For the period spanning 2002-2012, commercial pilots showed a
      lower fatality rate. Under visual meteorologic conditions, aerodynamic stall was
      a frequent cause for fatal accidents affecting both airman cohorts equally. For
      operations in instrument meteorologic conditions, fatal accidents were most
      commonly attributed to instrument approach deficiency and spatial disorientation.
      At night, failure to maintain obstacle/terrain clearance was the most prevalent
      cause of fatal crashes. CONCLUSION: Our data suggest that charity air medical
      transportation organizations should encourage their pilots to acquire commercial
      certification. Furthermore, our study indicates areas in which general aviation
      training/currency should be directed to reduce fatal accidents.

PMID- 26206544
TI  - The Need for a UK Helicopter Emergency Medical Service by Night: A Prospective,
      Simulation Study.
AB  - BACKGROUND: Major trauma commonly occurs at night. Helicopter emergency medical
      services (HEMS) can provide advanced prehospital care to victims of major trauma
      but do not routinely operate at night in the United Kingdom. We sought to
      prospectively examine the need for a night HEMS service in Kent, Surrey, and
      Sussex in the United Kingdom. METHODS: A 4-month, prospective study was conducted
      (July 1, 2012-October 31, 2012). HEMS dispatch paramedics were present in the
      ambulance dispatch center and undertook simulated HEMS activations when a
      suitable case was identified. All trauma cases from the 4-month study period were
      collated. Five independent HEMS clinicians reviewed the simulated tasking and
      trauma cases and gave an opinion on whether the patient met HEMS activation
      criteria. RESULTS: A mission rate of 1 case per night was predefined as cost
      effective. During the prospective study, 145 calls were identified by the HEMS
      dispatch paramedic as appropriate for an HEMS response. If HEMS had deployed to
      all 145 incidents, this would have resulted in an average mission rate of 1.2
      activations per night. Two hundred eight incidents were identified as potentially
      appropriate for HEMS activation. Responding to all 208 incidents would have
      resulted in a mean activation rate of 1.7 per night. CONCLUSION: This study
      justifies the need for Kent, Surrey and Sussex Air Ambulance Trust to operate a
      service at night for a trial period, with an estimated average mission load of 1
      per night spread over the entire night period. Further research is warranted to
      determine the potential impact of a night HEMS service on outcome from major
      trauma.

PMID- 26206545
TI  - Safety and Effectiveness of Whole Body Cooling Therapy for Neonatal
      Encephalopathy on Transport.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety and effectiveness
      of a transport protocol using active and passive methods for therapeutic whole
      body cooling of the neonate with hypoxic-ischemic encephalopathy. METHODS: A
      retrospective study of neonates who received whole body cooling during transport
      by our pediatric/neonatal transport team between December 2008 and April 2012 was
      conducted. RESULTS: Sixty-three of 66 (95%) neonates arrived within a safety
      temperature range of 33.0 degrees C-37 degrees C, and 3 (5%) were hypothermic
      (31.9 degrees C-32.8 degrees C). No clinical complications of cooling during
      transport were identified. Twenty-five (38%) and 57(86%) achieved therapeutic
      cooling upon admission and <= 6 hours after birth, respectively. Factors
      associated with cooling > 6 hours included a later time of initial referral (2.44
      vs. 1.07 hours, P = .01), a later rendezvous time (4.17 vs. 1.92 hours, P =
      .002), and a later admission time (6.46 vs. 3.99 hours, P = .001). CONCLUSION:
      Whole body cooling of neonates with hypoxic-ischemic encephalopathy can be
      effectively and safely performed during interfacility transport.

PMID- 26206546
TI  - Interhospital Transfer Center Model: Components, Themes, and Design Elements.
AB  - OBJECTIVE: Timely access to advanced and specialist treatment often requires
      rapid interhospital transfer of patients from community hospitals to tertiary
      care centers. Transfer systems are variable in structure and process and are
      described in the literature as being fragmented, complex, and difficult to
      navigate. METHODS: Nonparticipant observation at 10 tertiary care transfer
      systems. RESULTS: Identified core components (ie, primary transfer system
      answering point, bed management coordination, and transport team dispatch) are
      essential elements of an interhospital tertiary care transfer center. CONCLUSION:
      The Interhospital Transfer Center Model provides a useful framework to guide the
      design, implementation, and evaluation of interhospital transfer systems.

PMID- 26206547
TI  - Comparison of a Padded Patient Litter and Long Spine Board for Spinal
      Immobilization in Air Medical Transport.
AB  - OBJECTIVE: The long spinal board is the immobilization standard during
      prehospital transport. The flat surface of the board increases the pressure
      placed on both the thoracic kyphosis and the sacrum and increases the risk for
      pressure ulcers. This study compared patient stability and comfort between a
      padded litter system used in air medical transport and the long spine board.
      METHODS: The study was completed at a large 350-bed Magnet Recognized nonteaching
      hospital. The hospital owns and operates an air medical transport service.
      Subjects were secured to a padded litter and a long spinal board with a cervical
      collar and head blocks and 3 straps. Laser pointers were used to mark neutral at
      points on the subject's head, sternum, and pelvis. The subject was tilted 45
      degrees left and right with movement measured in inches. Comfort level was
      measured before and after. Paired t-tests were used to detect differences in
      movement. RESULTS: No statistical difference in movement was found between
      devices for the head; however, there was statistically significant greater
      movement on the padded litter for the sternum and pelvis. CONCLUSION: The padded
      litter did not immobilize as tightly as the long board although the effect of the
      differences was small.

PMID- 26206548
TI  - Noninvasive Mechanical Ventilation in Helicopter Emergency Medical Services Saves
      Time and Oxygen and Improves Patient and Mission Safety: A Pilot Study.
AB  - Noninvasive mechanical ventilation (NIMV) is used increasingly in patients with
      severe respiratory distress and has clear benefits over standard medical therapy
      (SMT) in terms of patient safety. NIMV is particularly useful in cardiogenic
      acute pulmonary edema and in exacerbations of chronic obstructive pulmonary
      disease, both of which are frequent reasons for an emergency medical services
      dispatch. Early use of NIMV avoids complications in these patients in many cases.
      To date, the use of noninvasive positive-pressure ventilation in the air medical
      environment has been minimally researched. We evaluated NIMV versus SMT in the
      helicopter emergency medical services environment in patients with cardiogenic
      acute pulmonary edema and exacerbated chronic obstructive pulmonary disease. The
      parameters assessed were stabilization time, tolerance, safety, clinical
      response, and oxygen consumption. Bilevel noninvasive positive-pressure
      ventilation was the ventilatory mode used for all patients. The technique of NIMV
      in medical air transport is useful, easy to operate, and safe. It offers
      increased patient safety, reducing the need for invasive mechanical ventilation
      and its complications; better intervention times (35.8 minutes [NIMV] vs. 57.65
      minutes [SMT], P < .05); improvement in aircraft operability; and a reduction in
      oxygen consumption (6.2 L/min vs. 9.8 L/min, P < .05), contributing to mission
      operability and safety. 

PMID- 26206550
TI  - Computational reverse shoulder prosthesis model: Experimental data and
      verification.
AB  - The reverse shoulder prosthesis aims to restore the stability and function of
      pathological shoulders, but the biomechanical aspects of the geometrical changes
      induced by the implant are yet to be fully understood. Considering a large-scale
      musculoskeletal model of the upper limb, the aim of this study is to evaluate how
      the Delta reverse shoulder prosthesis influences the biomechanical behavior of
      the shoulder joint. In this study, the kinematic data of an unloaded abduction in
      the frontal plane and an unloaded forward flexion in the sagittal plane were
      experimentally acquired through video-imaging for a control group, composed of 10
      healthy shoulders, and a reverse shoulder group, composed of 3 reverse shoulders.
      Synchronously, the EMG data of 7 superficial muscles were also collected. The
      muscle force sharing problem was solved through the minimization of the metabolic
      energy consumption. The evaluation of the shoulder kinematics shows an increase
      in the lateral rotation of the scapula in the reverse shoulder group, and an
      increase in the contribution of the scapulothoracic joint to the shoulder joint.
      Regarding the muscle force sharing problem, the musculoskeletal model estimates
      an increased activity of the deltoid, teres minor, clavicular fibers of the
      pectoralis major, and coracobrachialis muscles in the reverse shoulder group. The
      comparison between the muscle forces predicted and the EMG data acquired revealed
      a good correlation, which provides further confidence in the model. Overall, the
      shoulder joint reaction force was lower in the reverse shoulder group than in the
      control group. 

PMID- 26206551
TI  - Toward isometric force capabilities evaluation by using a musculoskeletal model:
      Comparison with direct force measurement.
AB  - Developing formalisms to determine force capabilities of human limbs by using
      musculoskeletal models could be useful for biomechanical and ergonomic
      applications. In this framework, the purpose of this study was to compare
      measured maximal isometric force capabilities at the hand in a set of Cartesian
      directions with forces computed from a musculoskeletal model of the upper-limb.
      The results were represented under the form of a measured force polytope (MFP)
      and a musculoskeletal force polytope (MSFP). Both of them were obtained from the
      convex hull of measured and simulated force vectors endpoints. Nine subjects
      participated to the experiment. For one posture recorded with an optoelectronic
      system, maximum isometric forces exerted at the hand were recorded in twenty six
      directions of the Cartesian space with a triaxial force sensor. Results showed
      significant differences between the polytopes global shapes. The MSFP was more
      elongated than the MFP. Concerning the polytopes volumes, no significant
      difference was found. Mean maximal isometric forces provided by MFP and MSFP were
      509.6 (118.4)N and 627.9 (73.3)N respectively. Moreover, the angle between the
      main axes of the two polytopes was 5.5 (2.3) degrees  on average. Finally, RMS
      error values between MFP and MSFP were lower than 100N in 88% of the considered
      directions. The proposed MSFP based on a musculoskeletal model gave interesting
      information on optimal force orientation parameters. The possible applications in
      the frame of ergonomics, rehabilitation and biomechanics are proposed and
      discussed.

PMID- 26206553
TI  - Incorporation of Zn(2+) ions into BaTiO3:Er(3+)/Yb(3+) nanophosphor: an effective
      way to enhance upconversion, defect luminescence and temperature sensing.
AB  - Ferroelectric BaTiO3 became a multifunctional material via doping of lanthanide
      ions (0.3 mol% Er(3+)/3.0 mol% Yb(3+)) and subsequently upconversion luminescence
      was enhanced by incorporation of Zn(2+) ions. Upconversion luminescence of
      BaTiO3:Er(3+)/Yb(3+) perovskite nanophosphor has been studied using 800 and 980
      nm laser excitations. The emission dynamics is studied with respect to its
      dependence on input power and external temperature including lifetime. Based on
      time-resolved spectroscopy, it is inferred that two types of Er(3+) sites are
      present in the barium titanate lattice. The first one is a short lived component
      (minor species) present at 6-coordinated Ti-sites of low symmetry while the
      second one is a long lived component (major species), present at 12-coordinated
      Ba-sites with high symmetry. The influence of the introduction of Zn(2+) ions on
      the lifetime of (4)S3/2 and (4)F9/2 levels of Er(3+) ions is also investigated.
      Enhanced temperature sensing performance (120 K to 505 K) of the material is
      observed using the fluorescence intensity ratio technique, employing the emission
      from the thermally coupled, (2)H11/2 and (4)S3/2 energy levels of Er(3+) ions.
      The defect luminescence of the material is also found to increase upon Zn-doping.

PMID- 26206552
TI  - Impact of cigarette smoke extract and hyperglycemic conditions on blood-brain
      barrier endothelial cells.
AB  - BACKGROUND: Diabetes and tobacco smoking are significant public health concerns
      which have been shown to independently impact the blood-brain barrier (BBB).
      Since smoking is a risk factor for diabetes and shares some of the common
      pathological pathways leading to metabolic abnormalities, it is hypothesized that
      their combination would produce additive or synergistic BBB dysfunction.
      Therefore, the objective of this study was to assess this hypothesis and evaluate
      the magnitude of these effects in vitro using hCMEC/D3 cells; a well-established
      human BBB endothelial cell line. METHODS: Monolayers of hCMEC/D3 cells were
      exposed to hyperglycemic conditions (HG; 35 mM) or 5% soluble cigarette smoke
      extracts (CSE, model of mainstream smoke exposure) for 12-24 h. Cells were then
      harvested for subsequent biochemical analyses. Transendothelial electrical
      resistance (TEER) and paracellular permeability to florescent dextrans were used
      to assess monolayer integrity. Analysis of released factors and cytokines was
      carried out by ELISA. Western blot (WB) analysis/immunofluorescence of relevant
      molecular targets was carried out. P-gp efflux activity was measured using
      rhodamine 123. RESULTS: Immunofluorescence and WB data showed a significant ZO-1
      down-regulation by HG and/or CSE over 24 h exposure. CSE in presence of HG
      produced a synergistic increase in release of vascular endothelial growth factor
      that was accompanied by decreased TEER and augmented permeability to labeled
      dextrans in a size-dependent manner. Moreover, CSE increased the expression of
      GLUT-1 and SGLT-1 in isolated membrane fractions of hCMEC/D3 cells. The effect
      was amplified by HG. Both, HG and CSE elicited the membrane upregulation of P
      glycoprotein (P-gp) expression which however, was not paralleled by a comparable
      efflux activity. Interestingly, concomitant exposure to HG and CSE evoked a
      marked upregulation of PECAM-1 and other pro-inflammatory markers including IL-6
      and -8, when compared to each condition alone. Moreover, exposure to all tested
      conditions amplified (to a different degree) cellular oxidative stress response
      denoted by increased Nrf2 nuclear translocation. CONCLUSION: Overall, our results
      have clearly shown an additive pattern in the release of angiogenic and
      inflammatory factors following concomitant exposure to HG and CSE. This suggests
      the involvement of common key modulators in BBB impairment by both CS and HG
      possibly through the activation of oxidative stress responses.

PMID- 26206554
TI  - Salt-water imbalance and fluid overload in hemodialysis patients: a pivotal role
      of corin.
AB  - Natriuretic peptides (NP) play a key role in regulation of salt and water
      balance. Corin, a serine protease which activates NP, plays a key role in
      regulation of blood pressure and cardiac function. The aim of the study was to
      evaluate the involvement of corin in renal physiopathology, analyze its levels in
      dialyzed patients and evaluate its relation with fluid overload and comorbidities
      such as heart failure and blood hypertension. We studied serum corin in uremic
      patients (n = 20) undergoing hemodialysis therapy (HD) and in healthy subjects
      (HS). Corin levels in uremic patients were higher than in HS (p < 0.0001).
      Moreover, its concentration did not change after a single HD session.
      Hypertensive patients and subject suffering from heart failure were characterized
      by high values of corin. After multivariate analysis, direct correlations were
      maintained between corin and dialysis vintage (beta = 0.83; p = 0.0002), heart
      failure (beta = 0.42; p < 0.0001), systolic blood pressure (beta = -0.70; p =
      0.0002) and body weight (beta = -0.39; p < 0.0001). Corin might be implicated in
      the regulation of salt and water balance and the disturbances of volume
      homeostasis of HD patients. However, further studies are warranted to understand
      the role of corin in kidney diseases and to define its diagnostic and prognostic
      role. 

PMID- 26206555
TI  - Stathmin 1 and p16(INK4A) are sensitive adjunct biomarkers for serous tubal
      intraepithelial carcinoma.
AB  - OBJECTIVE: To credential Stathmin 1 (STMN1) and p16(INK4A) (p16) as adjunct
      markers for the diagnosis of serous tubal intraepithelial carcinoma (STIC), and
      to compare STMN1 and p16 expression in p53-positive and p53-negative STIC and
      invasive high-grade serous carcinoma (HGSC). METHODS: Immunohistochemistry (IHC)
      was used to examine STMN1 and p16 expression in fallopian tube specimens (n=31)
      containing p53-positive and p53-negative STICs, invasive HGSCs, and
      morphologically normal FTE (fallopian tube epithelium). STMN1 and p16 expression
      was scored semiquantitatively by four individuals. The semiquantitative scores
      were dichotomized, and reported as positive or negative. Pooled siRNA was used to
      knockdown p53 in a panel of cell lines derived from immortalized FTE and HGSC.
      RESULTS: STMN1 and p16 were expressed in the majority of p53-positive and p53
      negative STICs and concomitant invasive HGSCs, but only scattered positive cells
      were present in morphologically normal FTE. Both proteins were expressed
      consistently across multiple STICs from the same patient and in concomitant
      invasive HGSC. Knockdown of p53 in immortalized FTE cells and in four HGSC
      derived cell lines expressing different missense p53 mutations did not affect
      STMN1 protein levels. CONCLUSIONS: This study demonstrates that STMN1 and p16 are
      sensitive and specific adjunct biomarkers that, when used with p53 and Ki-67,
      improve the diagnostic accuracy of STIC. The addition of STMN1 and p16 helps to
      compensate for practical limitations of p53 and Ki-67 that complicate the
      diagnosis in up to one third of STICs.

PMID- 26206556
TI  - Discovery of a Single Monooxygenase that Catalyzes Carbamate Formation and Ring
      Contraction in the Biosynthesis of the Legonmycins.
AB  - Pyrrolizidine alkaloids (PAs) are a group of natural products with important
      biological activities. The discovery and characterization of the multifunctional
      FAD-dependent enzyme LgnC is now described. The enzyme is shown to convert
      indolizidine intermediates into pyrrolizidines through an unusual ring
      expansion/contraction mechanism, and catalyze the biosynthesis of new bacterial
      PAs, the so-called legonmycins. By genome-driven analysis, heterologous
      expression, and gene inactivation, the legonmycins were also shown to originate
      from non-ribosomal peptide synthetases (NRPSs). The biosynthetic origin of
      bacterial PAs has thus been disclosed for the first time. 

PMID- 26206557
TI  - Mast Cells Infiltrating Inflamed or Transformed Gut Alternatively Sustain Mucosal
      Healing or Tumor Growth.
AB  - Mast cells (MC) are immune cells located next to the intestinal epithelium with
      regulatory function in maintaining the homeostasis of the mucosal barrier. We
      have investigated MC activities in colon inflammation and cancer in mice either
      wild-type (WT) or MC-deficient (Kit(W-sh)) reconstituted or not with bone marrow
      derived MCs. Colitis was chemically induced with dextran sodium sulfate (DSS).
      Tumors were induced by administering azoxymethane (AOM) intraperitoneally before
      DSS. Following DSS withdrawal, Kit(W-sh) mice showed reduced weight gain and
      impaired tissue repair compared with their WT littermates or Kit(W-sh) mice
      reconstituted with bone marrow-derived MCs. MCs were localized in areas of
      mucosal healing rather than damaged areas where they degraded IL33, an alarmin
      released by epithelial cells during tissue damage. Kit(W-sh) mice reconstituted
      with MC deficient for mouse mast cell protease 4 did not restore normal mucosal
      healing or reduce efficiently inflammation after DSS withdrawal. In contrast with
      MCs recruited during inflammation-associated wound healing, MCs adjacent to
      transformed epithelial cells acquired a protumorigenic profile. In AOM- and DSS
      treated WT mice, high MC density correlated with high-grade carcinomas. In
      similarly treated Kit(W-sh) mice, tumors were less extended and displayed lower
      histologic grade. Our results indicate that the interaction of MCs with
      epithelial cells is dependent on the inflammatory stage, and on the activation of
      the tissue repair program. Selective targeting of MCs for prevention or treatment
      of inflammation-associated colon cancer should be timely pondered to allow tissue
      repair at premalignant stages or to reduce aggressiveness at the tumor stage.

PMID- 26206559
TI  - Tumor-Promoting Effects of Myeloid-Derived Suppressor Cells Are Potentiated by
      Hypoxia-Induced Expression of miR-210.
AB  - Myeloid-derived suppressor cells (MDSC) contribute significantly to the malignant
      characters conferred by hypoxic tumor microenvironments. However, selective
      biomarkers of MDSC function in this critical setting have not been defined. Here,
      we report that miR-210 expression is elevated by hypoxia-inducible factor-1alpha
      (HIF1alpha) in MDSC localized to tumors, compared with splenic MDSC from tumor
      bearing mice. In tumor MDSC, we determined that HIF1alpha was bound directly to a
      transcriptionally active hypoxia-response element in the miR-210 proximal
      promoter. miR-210 overexpression was sufficient to enhance MDSC-mediated T-cell
      suppression under normoxic conditions, while targeting hypoxia-induced miR-210
      was sufficient to decrease MDSC function against T cells. Mechanistic
      investigations revealed that miR-210 modulated MDSC function by increasing
      arginase activity and nitric oxide production, without affecting reactive oxygen
      species, IL6, or IL10 production or expression of PD-L1. In splenic MDSC, miR-210
      regulated Arg1, Cxcl12, and IL16 at the levels of both mRNA and protein, the
      reversal of which under normoxic conditions decreased T-cell-suppressive effects
      and IFNgamma production. Interestingly, miR-210 overexpression or targeting IL16
      or CXCL12 enhanced the immunosuppressive activity of MDSC in vivo, resulting in
      increased tumor growth. Taken together, these results provide a preclinical
      rationale to explore miR-210 inhibitory oligonucleotides as adjuvants to boost
      immunotherapeutic responses in cancer patients.

PMID- 26206561
TI  - James Roger: A brief biography.

PMID- 26206558
TI  - ErbB3-ErbB2 Complexes as a Therapeutic Target in a Subset of Wild-type BRAF/NRAS
      Cutaneous Melanomas.
AB  - The treatment options remain limited for patients with melanoma who are wild-type
      for both BRAF and NRAS (WT/WT). We demonstrate that a subgroup of WT/WT melanomas
      display high basal phosphorylation of ErbB3 that is associated with autocrine
      production of the ErbB3 ligand neuregulin-1 (NRG1). In WT/WT melanoma cells
      displaying high levels of phospho-ErbB3, knockdown of NRG1 reduced cell viability
      and was associated with decreased phosphorylation of ErbB3, its coreceptor ErbB2,
      and its downstream target, AKT. Similar effects were observed by targeting ErbB3
      with either siRNAs or the neutralizing ErbB3 monoclonal antibodies huHER3-8 and
      NG33. In addition, pertuzumab-mediated inhibition of ErbB2 heterodimerization
      decreased AKT phosphorylation, cell growth in vitro, and xenograft growth in
      vivo. Pertuzumab also potentiated the effects of MEK inhibitor on WT/WT melanoma
      growth in vitro and in vivo. These findings demonstrate that targeting ErbB3
      ErbB2 signaling in a cohort of WT/WT melanomas leads to tumor growth reduction.
      Together, these studies support the rationale to target the NRG1-ErbB3-ErbB2 axis
      as a novel treatment strategy in a subset of cutaneous melanomas.

PMID- 26206560
TI  - Warfarin Blocks Gas6-Mediated Axl Activation Required for Pancreatic Cancer
      Epithelial Plasticity and Metastasis.
AB  - Repurposing "old" drugs can facilitate rapid clinical translation but
      necessitates novel mechanistic insight. Warfarin, a vitamin K "antagonist" used
      clinically for the prevention of thrombosis for more than 50 years, has been
      shown to have anticancer effects. We hypothesized that the molecular mechanism
      underlying its antitumor activity is unrelated to its effect on coagulation, but
      is due to inhibition of the Axl receptor tyrosine kinase on tumor cells.
      Activation of Axl by its ligand Gas6, a vitamin K-dependent protein, is inhibited
      at doses of warfarin that do not affect coagulation. Here, we show that
      inhibiting Gas6-dependent Axl activation with low-dose warfarin, or with other
      tumor-specific Axl-targeting agents, blocks the progression and spread of
      pancreatic cancer. Warfarin also inhibited Axl-dependent tumor cell migration,
      invasiveness, and proliferation while increasing apoptosis and sensitivity to
      chemotherapy. We conclude that Gas6-induced Axl signaling is a critical driver of
      pancreatic cancer progression and its inhibition with low-dose warfarin or other
      Axl-targeting agents may improve outcome in patients with Axl-expressing tumors.

PMID- 26206563
TI  - Sarcopenia and nonalcoholic fatty liver disease: New evidence for low vitamin D
      status contributing to the link.

PMID- 26206562
TI  - CT Imaging Biomarkers of Bone Damage Induced by Environmental Level of Cadmium
      Exposure in Male Rats.
AB  - Cadmium (Cd) can induce bone loss and osteoporosis. Histologic methods have shown
      that Cd can induce microarchitecture change of the trabecular bone. The aim of
      this study is to evaluate the imaging biomarkers of osteoporosis induced by Cd
      using micro-computed tomography (micro-CT). Twenty-four male Sprague-Dawley rats
      were randomly divided into four groups that were exposed to Cd via drinking water
      at concentrations of 0, 2, 10, and 50 mg/L for 3 months. Before sacrifice, micro
      CT scanning was performed on the proximal tibia. Three-dimensional images were
      analyzed by using commercial software to measure apparent bone mineral density
      (ABMD), tissue bone mineral density (TBMD), bone volume/total volume fraction
      (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular
      separation (Tb.Sp), and structural model index (SMI) as imaging biomarkers.
      Histologic analyses were performed using hematoxylin and eosin (HE) and Goldner's
      trichrome stain. Exposure to Cd resulted in a marked decrease of ABMD, BV/TV, and
      Tb.N and an increase of Tb.Sp and SMI compared with control, especially for those
      treated with 50 mg Cd/L (p < 0.05). Decreased Tb.N and increased Tb.Sp compared
      to that of control were also observed in histologic findings. The micro-CT
      imaging is a promising tool for assessing the bone damage induced by Cd, and
      Tb.N, Tb.Sp, and SMI may be the potential sensitive imaging biomarkers. 

PMID- 26206565
TI  - Better balance, fewer falls.

PMID- 26206564
TI  - Ethnic differences in resting metabolic rate, respiratory quotient and body
      temperature: a comparison of Africans and European Australians.
AB  - PURPOSE: A comparison of resting metabolic rate (RMR), respiratory quotient (RQ)
      and body temperature between adults of African and European descent. METHOD:
      Twenty-nine sub-Saharan Africans (SSA; 13 men and 16 women) and thirty-two
      Australians of European descent (EUR; eight men and 24 women) had RMR and RQ
      measured by indirect calorimetry. Dual-energy X-ray absorptiometry was used to
      determine fat mass (FM), fat-free mass, bone mineral content (BMC), appendicular
      lean tissue mass and non-appendicular lean tissue mass. Total skeletal muscle
      mass (SMM) was predicted. Residual mass (RM) was the difference between body
      weight and the sum of FM, SMM and BMC. The short form of the International
      Physical Activity Questionnaire was used to determine habitual physical activity
      (PA). Tympanic in the ear temperature (IET) and forearm to fingertip temperature
      gradients (FFG) were monitored throughout the protocol. RESULTS: The unadjusted
      RMR of SSA was significantly lower compared to EUR. Adjusted for age, sex,
      season, PA, FM, BMC, SMM and RM, this difference in RMR was still evident (mean
      +/- SE, SSA: 4880 +/- 161 kJ/d vs. EUR: 5979 +/- 111, P < 0.005). The same model
      of adjustment also uncovered a significantly lower adjusted IET (SSA: 35.26 
      degrees C +/- 0.133 vs. EUR: 35.60 +/- 0.091, P < 0.05), a higher adjusted RQ
      (SSA: 0.86 +/- 0.014 vs. EUR: 0.83 +/- 0.010, P < 0.05) but no difference in
      adjusted FFG. CONCLUSIONS: In this study, SSA had a lower RMR, higher RQ and
      lower IET relative to EUR Australians.

PMID- 26206567
TI  - Therapeutic and Prophylactic Potential of Morama (Tylosema esculentum): A Review.
AB  - Tylosema esculentum (morama) is a highly valued traditional food and source of
      medicine for the San and other indigenous populations that inhabit the arid to
      semi-arid parts of Southern Africa. Morama beans are a rich source of phenolic
      acids, flavonoids, certain fatty acids, non-essential amino acids, certain
      phytosterols, tannins and minerals. The plant's tuber contains griffonilide,
      behenic acid and starch. Concoctions of extracts from morama bean, tuber and
      other local plants are frequently used to treat diarrhoea and digestive disorders
      by the San and other indigenous populations. Information on composition and
      bioactivity of phytochemical components of T. esculentum suggests that the
      polyphenol-rich extracts of the bean testae and cotyledons have great potential
      as sources of chemicals that inhibit infectious microorganisms (viral, bacterial
      and fungal, including drug-resistant strains), offer protection against certain
      non-communicable diseases and promote wound healing and gut health. The potential
      antinutritional properties of a few morama components are also highlighted. More
      research is necessary to reveal the full prophylactic and therapeutic potential
      of the plant against diseases of the current century. Research on domestication
      and conservation of the plant offers new hope for sustainable utilisation of the
      plant.

PMID- 26206566
TI  - Developmental disruptions underlying brain abnormalities in ciliopathies.
AB  - Primary cilia are essential conveyors of signals underlying major cell functions.
      Cerebral cortical progenitors and neurons have a primary cilium. The significance
      of cilia function for brain development and function is evident in the plethora
      of developmental brain disorders associated with human ciliopathies.
      Nevertheless, the role of primary cilia function in corticogenesis remains
      largely unknown. Here we delineate the functions of primary cilia in the
      construction of cerebral cortex and their relevance to ciliopathies, using an
      shRNA library targeting ciliopathy genes known to cause brain disorders, but
      whose roles in brain development are unclear. We used the library to query how
      ciliopathy genes affect distinct stages of mouse cortical development, in
      particular neural progenitor development, neuronal migration, neuronal
      differentiation and early neuronal connectivity. Our results define the
      developmental functions of ciliopathy genes and delineate disrupted developmental
      events that are integrally related to the emergence of brain abnormalities in
      ciliopathies. 

PMID- 26206570
TI  - Photobioreactors in Life Support Systems.
AB  - Life support systems for long-term space missions or extraterrestrial
      installations have to fulfill major functions such as purification of water and
      regeneration of atmosphere as well as the generation of food and energy. For
      almost 60 years ideas for biological life support systems have been collected and
      various concepts have been developed and tested. Microalgae as photosynthetic
      organisms have played a major role in most of these concepts. This review deals
      with the potentials of using eukaryotic microalgae for life support systems and
      highlights special requirements and frame conditions for designing space
      photobioreactors especially regarding illumination and aeration. Mono- and
      dichromatic illumination based on LEDs is a promising alternative for
      conventional systems and preliminary results yielded higher photoconversion
      efficiencies (PCE) for dichromatic red/blue illumination than white illumination.
      Aeration for microgravity conditions should be realized in a bubble-free manner,
      for example, via membranes. Finally, a novel photobioreactor concept for space
      application is introduced being parameterized and tested with the microalga
      Chlamydomonas reinhardtii. This system has already been tested during two
      parabolic flight campaigns.

PMID- 26206568
TI  - Potential Occupational Exposures and Health Risks Associated with Biomass-Based
      Power Generation.
AB  - Biomass is increasingly being used for power generation; however, assessment of
      potential occupational health and safety (OH&S) concerns related to usage of
      biomass fuels in combustion-based generation remains limited. We reviewed the
      available literature on known and potential OH&S issues associated with biomass
      based fuel usage for electricity generation at the utility scale. We considered
      three potential exposure scenarios--pre-combustion exposure to material
      associated with the fuel, exposure to combustion products, and post-combustion
      exposure to ash and residues. Testing of dust, fungal and bacterial levels at two
      power stations was also undertaken. Results indicated that dust concentrations
      within biomass plants can be extremely variable, with peak levels in some areas
      exceeding occupational exposure limits for wood dust and general inhalable dust.
      Fungal spore types, identified as common environmental species, were higher than
      in outdoor air. Our review suggests that pre-combustion risks, including
      bioaerosols and biogenic organics, should be considered further. Combustion and
      post-combustion risks appear similar to current fossil-based combustion. In light
      of limited available information, additional studies at power plants utilizing a
      variety of technologies and biomass fuels are recommended.

PMID- 26206569
TI  - Smoking Prevalence and Associated Factors as well as Attitudes and Perceptions
      towards Tobacco Control in Northeast China.
AB  - OBJECTIVES: The present study aimed to investigate the prevalence of smoking and
      environmental tobacco smoke (ETS), the associated factors of current smoking
      among adults, and their attitudes and perceptions towards tobacco control.
      METHODS: A population-based cross-sectional survey was conducted in 2012 using a
      self-reported questionnaire. A representative sample of adults aged 18-79 years
      was collected in the Jilin Province of Northeast China by a multistage stratified
      random cluster sampling design. Descriptive data analysis was conducted, and 95%
      confidence intervals (CI) of prevalence/frequency were calculated to enable
      comparisons between the alleged differences and similarities. Multivariable
      logistic regressions were used to examine the risk factors associated with
      current smoking. RESULTS: 21,435 adults responded to the survey (response rate:
      84.9%). The overall prevalence of ever smoking, current smoking, and former
      smoking or smoking cessation was 39.1% (95% CI: 38.3-39.9), 31.8% (95% CI 31.1
      32.6), and 7.3% (95% CI: 6.9-7.7), respectively. The proportion of ETS exposure
      among adult non-smokers in Jilin Province was 61.1% (95% CI: 60.1-62.1), and
      23.1% (95% CI: 22.3-24.0) of the non-smokers reported daily ETS exposure. The
      proportion of ETS exposure at home was 33.4% (95% CI: 32.5-34.4), but the
      proportion of ETS exposure at restaurants was lower (6.5%) (95% CI: 6.0-7.1).
      More than 90% of the participants had positive attitudes and perceptions towards
      tobacco control, but 23.2% (95% CI: 22.5-24.0) of them did not agree with the
      perception of "smoking is fully quit in public places", and almost half of the
      adults (49.5%) (95% CI: 48.7-50.3) did not agree with the perception of "hazards
      of low-tar cigarettes are equal to general cigarettes". CONCLUSIONS: Smoking and
      exposure to ETS are prevalent among adults from the Jilin Province of Northeast
      China. Our findings suggest that tobacco control should be advocated in Northeast
      China. Anti-smoking campaigns and legislation should be built into the public
      health curriculum and government policy.

PMID- 26206571
TI  - Cystic fibrosis-style changes in the early phase of pancreatitis.
AB  - The early phase of both acute and chronic pancreatitis can be characterized by
      disrupt level and function of the cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl(-) channel, decreased bicarbonate secretion, intraductal
      acidosis, decrease of fluid secretion and elevation of mucoprotein levels. It is
      almost needless to say that these intrapancreatic changes are very similar to the
      pathophysiological changes observed in cystic fibrosis. The aim of this mini
      review is to describe the development of the above mentioned pathological
      observations in details, moreover highlight some future therapeutic opportunities
      in pancreatitis. 

PMID- 26206572
TI  - New molecular therapies for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a major health problem. Mortality owing to
      liver cancer has increased in the past 20 years, with recent studies reporting an
      incidence of 780,000 cases/year. Most patients with hepatocellular carcinoma are
      still diagnosed at intermediate or advanced disease stages, where curative
      approaches are often not feasible. Among the treatment options available, the
      molecular targeted agent sorafenib is able to significantly increase overall
      survival in these patients. Afterwards, up to 7 randomized phase III clinical
      trials investigating other molecular therapies in the first-line and second-line
      settings have failed to improve survival. Potential reasons for this include
      intertumor heterogeneity, issues with trial design and a lack of predictive
      biomarkers of response. Advance in our knowledge of the human genome has provided
      a comprehensive picture of commonly mutated genes in patients with HCC including
      mutations in the TERT promoter, CTNNB1, TP53 and ARID1A along with other
      amplifications (FGF19, VEGFA) or homozygous deletions (p16) as the most frequent
      alterations. This knowledge points toward specific drivers as candidate for
      druggable therapies. Thus, progressive implementation of proof-of-concept and
      enrichment might improve results in clinical trials testing of molecular targeted
      agents. Ultimately, these studies are aimed at long-term to improve current
      standards of care and influenced clinical decision-making and practice
      guidelines.

PMID- 26206574
TI  - Reversibility of liver fibrosis.
AB  - Liver fibrosis is a serious health problem worldwide, which can be induced by a
      wide spectrum of chronic liver injuries. However, until today, there is no
      effective therapy available for liver fibrosis except the removal of underlying
      etiology or liver transplantation. Recent studies indicate that liver fibrosis is
      reversible when the causative agent(s) is removed. Understanding of mechanisms of
      liver fibrosis regression will lead to the identification of new therapeutic
      targets for liver fibrosis. This review summarizes recent research progress on
      mechanisms of reversibility of liver fibrosis. While most of the research has
      been focused on HSCs/myofibroblasts and inflammatory pathways, the crosstalk
      between different organs, various cell types and multiple signaling pathways
      should not be overlooked. Future studies that lead to fully understanding of the
      crosstalk between different cell types and the molecular mechanism underlying the
      reversibility of liver fibrosis will definitely give rise to new therapeutic
      strategies to treat liver fibrosis. 

PMID- 26206573
TI  - New therapies for hepatic fibrosis.
AB  - Liver fibrosis is an outcome of many chronic diseases, and often results in
      cirrhosis, liver failure, and portal hypertension. Liver transplantation is the
      only treatment available for patients with advanced stages of liver cirrhosis.
      Therefore, alternative methods are required to develop new strategies for anti
      fibrotic therapy. Various kinds of hepatocyte injuries cause inflammatory
      reactions, which lead to activation of hepatic stellate cells (HSCs). Continuous
      liver injuries maintain these activated HSCs, and they are called as
      myofibroblasts. Myofibroblasts proliferate in response to various kinds of
      cytokines and produce extracellular matrix proteins (ECMs). Myofibroblasts
      undergo apoptosis and inactivation when the underlying causative etiologies are
      cleared. Here, we describe the current knowledge of targeting the activated HSCs
      as a therapeutic target for liver fibrosis. 

PMID- 26206575
TI  - ALPD 2015, Preface.

PMID- 26206576
TI  - A case of phlebosclerotic colitis.

PMID- 26206577
TI  - Morphogen-related therapeutic targets for liver fibrosis.
AB  - Recent research on hepatic stellate cells (HSCs) has spotlighted the involvement
      of morphogens in their cell fate determination in liver fibrosis. Temporally and
      spatially expressed during embryonic development, morphogens are involved in
      regulation of cell proliferation and differentiation, and tissue patterning. In
      normal adult liver, morphogens are generally expressed at low levels. However, in
      liver disease, myofibroblastic HSCs express morphogens such as Wnt, Shh, Necdin,
      DLK1, and Notch as part of their participation in fibrogenesis and wound healing.
      Liver regeneration involves cell proliferation and differentiation akin to
      embryonic liver development where the cells appear to undergo similar fates, and
      not surprisingly the morphogens are re-activated for the regenerative purpose in
      adult liver injury. Evidence also points to crosstalk of these morphogens in
      regulation of HSC fate determination. Genetic ablation or pharmacologic
      inhibition of morphogens reverts activated HSC to quiescent cells in culture and
      attenuates progression of hepatic fibrosis. However, positive regulation of liver
      regeneration by the morphogens needs to be spared. Therapeutically, manipulation
      of morphogen activities in a cell type and phase-specific manner should offer new
      modalities for chronic liver disease. 

PMID- 26206578
TI  - Caveolin-1 promotes tumor growth and metastasis via autophagy inhibition in
      hepatocellular carcinoma.
AB  - BACKGROUND: Caveolin-1 is a member of the caveolae family of membrane proteins.
      Although some researchers have investigated the function of Caveolin-1 in
      hepatocellular carcinoma, the mechanism of Caveolin-1 action and its prognostic
      value in hepatocellular carcinoma remain unclear. METHODS: Caveolin-1 expression
      was measured in hepatocellular carcinoma cell lines and tissues using
      quantitative reverse transcription-polymerase chain reaction, western blot, and
      immunofluorescence assays. In in vitro experiments, Caveolin-1 was depleted using
      a short hairpin RNA lentiviral vector, and tumor cell behavior was analyzed. The
      effect of Caveolin-1 on hepatocellular carcinoma cell autophagy was investigated.
      Prognostic value of Caveolin-1 was analyzed by immunohistochemistry in two
      cohorts that included a total of 721 hepatocellular carcinoma patients. RESULTS:
      We found that Caveolin-1 was overexpressed in highly metastatic hepatocellular
      carcinoma cell lines and tumor tissues. Moreover, Caveolin-1 promoted
      hepatocellular carcinoma cell proliferation, migration, and angiogenesis and
      inhibited autophagy. Finally, Caveolin-1 expression in hepatocellular carcinoma
      tissues was inversely correlated with patient overall survival and time to
      recurrence. CONCLUSION: Our data obtained from cell lines suggest an oncogenic
      role for Caveolin-1 in hepatocellular carcinoma, Caveolin-1 contributed to
      hepatocellular carcinoma cell autophagy deficiency. Furthermore, Caveolin-1 may
      function as a novel prognostic indicator for hepatocellular carcinoma patients
      after curative resection, and combination of targeted therapy aimed at Caveolin-1
      and autophagy modulation may represent an effective way to treat hepatocellular
      carcinoma.

PMID- 26206579
TI  - Management of HCV in the liver transplant setting.
AB  - Hepatitis C-related cirrhosis is the main indication for liver transplantation.
      In the absence of viral eradication, viral recurrence leads to recurrent HCV
      disease and progression to advanced graft disease in many recipients,
      particularly those transplanted with subobtimal grafts. Viral eradication is
      associated with improved outcome whether used pre- or post-transplantation. In
      the new era of interferon-free regimes, this is now safe and feasible in most
      transplant candidates and transplant recipients. There are questions that remain
      unanswered, such as defining the point of no return where clinical improvement
      does not follow viral eradication or management of treatment failures.

PMID- 26206580
TI  - Distinct macrophage phenotype and collagen organization within the intraluminal
      thrombus of abdominal aortic aneurysm.
AB  - OBJECTIVE: Little is known about the etiologic factors that lead to the
      occurrence of intraluminal thrombus (ILT) during abdominal aortic aneurysm (AAA)
      development. Recent work has suggested that macrophages may play an important
      role in progression of a number of other vascular diseases, including
      atherosclerosis; however, whether these cells are present within the ILT of a
      progressing AAA is unknown. The purpose of this work was to define the presence,
      phenotype, and spatial distribution of macrophages within the ILT excised from
      six patients. We hypothesized that the ILT contains a population of activated
      macrophages with a distinct, nonclassical phenotypic profile. METHODS: ILT
      samples were examined using histologic staining and immunofluorescent labeling
      for multiple markers of activated macrophages (cluster of differentiation [CD]45,
      CD68, human leukocyte antigen-DR, matrix metalloproteinase 9) and the additional
      markers alpha-smooth muscle actin, CD34, CD105, fetal liver kinase-1, and
      collagen I and III. RESULTS: Histologic staining revealed a distinct laminar
      organization of collagen within the shoulder region of the ILT lumen and a
      spatially heterogeneous cell composition within the ILT. Most of the cellular
      constituents of the ILT were in the luminal region and predominantly expressed
      markers of activated macrophages but also concurrently expressed alpha-smooth
      muscle actin, CD105, and synthesized collagen I and III. CONCLUSIONS: This report
      presents evidence for the presence of a distinct macrophage population within the
      luminal region of AAA ILT. These cells express a set of markers indicative of a
      unique population of activated macrophages. The exact contributions of these
      previously unrecognized cells to ILT formation and AAA pathobiology remains
      unknown.

PMID- 26206581
TI  - Lesion complexity drives the cost of superficial femoral artery endovascular
      interventions.
AB  - OBJECTIVE: Patients who undergo endovascular treatment of superficial femoral
      artery (SFA) disease vary greatly in lesion complexity and treatment options.
      This study examined the association of lesion severity and cost of SFA stenting
      and to determine if procedure cost affects primary patency at 1 year. METHODS: A
      retrospective record review identified patients undergoing initial SFA stenting
      between January 1, 2010, and February 1, 2012. Medical records were reviewed to
      collect data on demographics, comorbidities, indication for the procedure,
      TransAtlantic Inter-Society Consensus (TASC) II severity, and primary patency.
      The interventional radiology database and hospital accounting database were
      queried to determine cost drivers of SFA stenting. Procedure supply cost included
      any item with a bar code used for the procedure. Associations between cost
      drivers and lesion characteristics were explored. Primary patency was determined
      using Kaplan-Meier survival curves and a log-rank test. RESULTS: During the study
      period, 95 patients underwent stenting in 98 extremities; of these, 61% of SFA
      stents were performed for claudication, with 80% of lesions classified as TASC II
      A or B. Primary patency at 1 year was 79% for the entire cohort. The mean total
      cost per case was $10,333. Increased procedure supply cost was associated with
      adjunct device use, the number of stents, and TASC II severity. Despite higher
      costs of treating more complex lesions, primary patency at 1 year was similar at
      80% for high-cost (supply cost >$4000) vs 78% for low-cost (supply cost <$4000)
      interventions. CONCLUSIONS: SFA lesion complexity, as defined by TASC II
      severity, drives the cost of endovascular interventions but does not appear to
      disadvantage patency at 1 year. Reimbursement agencies should consider
      incorporating disease severity into reimbursement algorithms for lower extremity
      endovascular interventions.

PMID- 26206582
TI  - In vitro effects of phenytoin and DAPT on MDA-MB-231 breast cancer cells.
AB  - Voltage-gated sodium channel (VGSC) activity enhances cell behaviors related to
      metastasis, such as motility, invasion, and oncogene expression. Neonatal
      alternative splice form of Nav1.5 isoform is expressed in metastatic breast
      cancers. Furthermore, aberrant Notch signaling pathway can induce oncogenesis and
      may promote the progression of breast cancers. In this study, we aimed to analyze
      the effect of the nNav1.5 inhibitor phenytoin and Notch signal inhibitor N-[N
      (3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine-t-butyl ester (DAPT) on triple
      negative breast cancer cell line (MDA-MB-231) via inhibition of nNav1.5 VGSC
      activity and Notch signaling, respectively. In order to determine the individual
      and combined effects of these inhibitors, the 4-[3-(4-iyodophenyl)-2-(4
      nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) test, wound healing
      assay, and zymography were performed to detect the proliferation, lateral
      motility, and matrix metalloproteinase-9 (MMP9) activity, respectively. The
      expressions of nNav1.5, Notch4, MMP9, and tissue inhibitor of metalloproteinases
      1 (TIMP1) were also detected by quantitative real-time reverse transcriptase
      polymerase chain reaction. DAPT caused an antiproliferative effect when the doses
      were higher than 10 uM, whereas phenytoin showed no inhibitory action either
      alone or in combination with DAPT on the MDA-MB-231 cells. Furthermore, it was
      found that the lateral motility was inhibited by both inhibitors; however, this
      inhibitory effect was partially rescued when they were used in combination.
      Meanwhile, the results showed that the MMP9 activity and the ratio of MMP9 mRNA
      to TIMP1 mRNA were only decreased by DAPT. Thus, we conclude that the combined
      effect of DAPT and phenytoin is not as beneficial as using DAPT alone on MDA-MB
      231 breast cancer cells. 

PMID- 26206583
TI  - Protein kinase Calpha inhibits myocardin-induced cardiomyocyte hypertrophy
      through the promotion of myocardin phosphorylation.
AB  - Myocardin plays a key role in the development of cardiac hypertrophy. However,
      the upstream signals that control the stability and transactivity of myocardin
      remain to be fully understood. The expression of protein kinase Calpha (PKCalpha)
      also induces cardiac hypertrophy. An essential downstream molecule of PKCalpha,
      extracellular signal-regulated kinase 1/2, was reported to negatively regulate
      the activities of myocardin. But, the effect of cooperation between PKCalpha and
      myocardin and the potential molecular mechanism by which PKCalpha regulates
      myocardin-mediated cardiac hypertrophy are unclear. In this study, a luciferase
      assay was performed using H9C2 cells transfected with expression plasmids for
      PKCalpha and myocardin. Surprisingly, the results showed that PKCalpha inhibited
      the transcriptional activity of myocardin. PKCalpha inhibited myocardin-induced
      cardiomyocyte hypertrophy, demonstrated by the decrease in cell surface area and
      fetal gene expression, in cardiomyocyte cells overexpressing PKCalpha and
      myocardin. The potential mechanism underlying the inhibition effect of PKCalpha
      on the function of myocardin is further explored. PKCalpha directly promoted the
      basal phosphorylation of endogenous myocardin at serine and threonine residues.
      In myocardin-overexpressing cardiomyocyte cells, PKCalpha induced the excessive
      phosphorylation of myocardin, resulting in the degradation of myocardin and a
      transcriptional suppression of hypertrophic genes. These results demonstrated
      that PKCalpha inhibits myocardin-induced cardiomyocyte hypertrophy through the
      promotion of myocardin phosphorylation. 

PMID- 26206585
TI  - Exhaled breath temperature measurement: Applicability in childhood.

PMID- 26206584
TI  - Cell cycle-dependent ubiquitylation and destruction of NDE1 by CDK5-FBW7
      regulates ciliary length.
AB  - Primary cilia start forming within the G1 phase of the cell cycle and continue to
      grow as cells exit the cell cycle (G0). They start resorbing when cells re-enter
      the cell cycle (S phase) and are practically invisible in mitosis. The mechanisms
      by which cilium biogenesis and disassembly are coupled to the cell cycle are
      complex and not well understood. We previously identified the centrosomal
      phosphoprotein NDE1 as a negative regulator of ciliary length and showed that its
      levels inversely correlate with ciliogenesis. Here, we identify the tumor
      suppressor FBW7 (also known as FBXW7, CDC4, AGO, or SEL-10) as the E3 ligase that
      mediates the destruction of NDE1 upon entry into G1. CDK5, a kinase active in
      G1/G0, primes NDE1 for FBW7-mediated recognition. Cells depleted of FBW7 or CDK5
      show enhanced levels of NDE1 and a reduction in ciliary length, which is
      corrected in cells depleted of both FBW7 or CDK5 and NDE1. These data show that
      cell cycle-dependent mechanisms can control ciliary length through a CDK5-FBW7
      NDE1 pathway. 

PMID- 26206586
TI  - Determining the effect of storage conditions on prothrombin time, activated
      partial thromboplastin time and fibrinogen concentration in rat plasma samples.
AB  - Coagulation parameters are usually included in clinical and preclinical safety
      studies to evaluate the effect of xenobiotics on the extrinsic or intrinsic
      pathways of coagulation. The analysis is generally performed at the time of
      terminal sacrifice where many activities are scheduled. Chances of delay in
      analysis are likely particularly when blood is collected for coagulation via the
      abdominal vena cava. This experiment was planned to assess the variations in
      coagulation parameters caused by delay in analysis as well as by storage
      conditions. Blood was collected from the posterior vena cava under isoflurane
      anesthesia, and the plasma was separated immediately. Coagulation parameters were
      evaluated at 0, 6, 24 and 48 h from the plasma stored at room temperature, as
      well as plasma stored under refrigerated and freezing conditions. Stability of
      the analytes in blood was also evaluated under refrigerated conditions for 6 h.
      All parameters were analyzed using a semi-automated coagulometer. Prothrombin
      time (PT) was stable under all three storage conditions for up to 6 h. Although
      statistically significant differences were observed for activated partial
      thromboplastin time (APTT) at room and refrigeration temperatures for up to 6 h,
      the difference was clinically non-relevant. Fibrinogen was found to be the most
      stable parameter that showed consistency in results even up to 48 h under all
      three storage conditions. Plasma for PT can be stored and analyzed without any
      significant changes for up to 6 h from the actual blood collection, while
      fibrinogen level testing can be extended for up to 48 h after collection under
      any storage condition. For reliable APTT results, plasma samples should be run
      immediately after collection. 

PMID- 26206587
TI  - A Direct, Concise, and Enantioselective Synthesis of 2-Substituted 4,4,4
      Trifluorobutane-1,3-diols Based on the Organocatalytic In Situ Generation of
      Unstable Trifluoroacetaldehyde.
AB  - A direct, concise, and enantioselective synthesis of 2-substituted 4,4,4
      trifluorobutane-1,3-diols based on the organocatalytic asymmetric direct aldol
      reaction of an ethyl hemiacetal of trifluoroacetaldehyde with various aldehydes
      was examined. A catalytic amount (30 mol %) of commercially available and
      inexpensive l-prolinamide is quite effective as an organocatalyst for the
      catalytic in situ generation of gaseous and unstable trifluoroacetaldehyde from
      its hemiacetal, and a successive asymmetric direct aldol reaction with various
      aldehydes in dichloromethane at 0  degrees C, followed by reduction with sodium
      borohydride, gives 2-substituted 4,4,4-trifluorobutane-1,3-diols in moderate to
      good yields (31-84%) with low diastereoselectivities and good to excellent
      enantioselectivities (64-97% ee).

PMID- 26206588
TI  - Developing Rapport with Children in Forensic Interviews: Systematic Review of
      Experimental Research.
AB  - The vast majority of guidelines recommend that developing rapport with children
      is essential for successful forensic child interviewing; however, the question
      remains as to whether there is a sufficient body of scientific research to
      generate evidence-based guidelines for developing rapport with children in legal
      contexts. To answer this question, we conducted a systematic review of the
      literature to identify experimental studies of the effects of rapport-building
      methods on the reliability of children's reports. Independent raters applied 12
      exclusion criteria to the 2,761 potentially relevant articles located by
      electronic and hand searches of the literature. Experimental studies were few.
      Although studies to date are a beginning, the overall scientific base is weak
      regarding even basic issues such as how to best define rapport and the efficacy
      of common rapport-building techniques. This systematic review highlights what we
      know, what we do not know, and how much more we need to know to create evidence
      based best practice. Recommendations for reshaping the research agenda are
      discussed.

PMID- 26206589
TI  - Magnetic frustration, short-range correlations and the role of the paramagnetic
      Fermi surface of PdCrO2.
AB  - Frustrated interactions exist throughout nature, with examples ranging from
      protein folding through to frustrated magnetic interactions. Whilst magnetic
      frustration is observed in numerous electrically insulating systems, in metals it
      is a rare phenomenon. The interplay of itinerant conduction electrons mediating
      interactions between localised magnetic moments with strong spin-orbit coupling
      is likely fundamental to these systems. Therefore, knowledge of the precise shape
      and topology of the Fermi surface is important in any explanation of the magnetic
      behaviour. PdCrO2, a frustrated metallic magnet, offers the opportunity to
      examine the relationship between magnetic frustration, short-range magnetic order
      and Fermi surface topology. By mapping the short-range order in reciprocal space
      and experimentally determining the electronic structure, we have identified the
      dual role played by the Cr electrons in which the itinerant ones on the nested
      paramagnetic Fermi surface mediate the frustrated magnetic interactions between
      local moments. 

PMID- 26206591
TI  - Faradic redox active material of Cu7S4 nanowires with a high conductance for
      flexible solid state supercapacitors.
AB  - The exploration of high Faradic redox active materials with the advantages of low
      cost and low toxicity has been attracting great attention for producing high
      energy storage supercapacitors. Here, the high Faradic redox active material of
      Cu7S4-NWs coated on a carbon fiber fabric (CFF) is directly used as a binder-free
      electrode for a high performance flexible solid state supercapacitor. The Cu7S4
      NW-CFF supercapacitor exhibits excellent electrochemical performance such as a
      high specific capacitance of 400 F g(-1) at the scan rate of 10 mV s(-1) and a
      high energy density of 35 Wh kg(-1) at a power density of 200 W kg(-1), with the
      advantages of a light weight, high flexibility and long term cycling stability by
      retaining 95% after 5000 charge-discharge cycles at a constant current of 10 mA.
      The high Faradic redox activity and high conductance behavior of the Cu7S4-NWs
      result in a high pseudocapacitive performance with a relatively high specific
      energy and specific power. Such a new type of pseudocapacitive material of Cu7S4
      NWs with its low cost is very promising for actual application in
      supercapacitors. 

PMID- 26206590
TI  - The Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for
      Molecularly Selected Patients with Non-Small Cell Lung Cancer: A Meta-Analysis of
      30 Randomized Controlled Trials.
AB  - OBJECTIVE: To determine the efficacy of first-generation epidermal growth factor
      receptor tyrosine kinase inhibitors (EGFR-TKIs) in molecularly selected patients
      with advanced non-small cell lung cancer (NSCLC), we performed this pooled
      analysis. METHOD: Randomized trials of EGFR-TKIs as treatment for advanced NSCLC
      were included for this meta-analysis. We used published hazard ratios (HRs), if
      available, or derived treatment estimates from other survival data. Pooled
      estimates of treatment efficacy of EGFR-TKIs in the selected patients by EGFR
      mutation status were calculated. RESULTS: Out of 2134 retrieved articles, 30
      randomized controlled trials (RCTs) enrolling more than 4053 patients with wild
      type EGFR tumors and 1592 patients with mutant EGFR tumors were identified. For
      EGFR mutant patients, EGFR-TKIs treatment improved progression-free survival
      (PFS) compared with chemotherapy: the summary HRs were 0.41 (p < 0.00001) for the
      first-line setting and 0.46 (p = 0.02) for second/third-line setting,
      respectively. Also, the same superior trend was found with TKIs maintenance over
      placebo (HR = 0.14, p < 0.00001) and with TKIs combined with chemotherapy over
      chemotherapy (HR = 0.49, p = .002) in both the first-line and maintenance therapy
      settings. For EGFR wild-type patients, EGFR-TKIs have fared worse than
      chemotherapy in the first-line setting (HR = 1.65, p = .03) and in the
      second/third-line setting (HR = 1.27, p = .005). However, EGFR-TKIs maintenance
      still produced a reduction of 19 % in the risk of progression over placebo (HR =
      0.81, p = .02). Furthermore, EGFR-TKIs added to chemotherapy as first-line
      treatment resulted in an improvement of PFS over chemotherapy alone in such wild
      type EGFR patients (HR = 0.82, p = .03). In overall survival (OS) analysis, only
      EGFR-TKIs single agent was inferior to chemotherapy in EGFR wild-type patients
      (HR = 1.13, p = .02). No statistically significant difference in terms of OS was
      observed in any other subgroup analysis. CONCLUSIONS: For EGFR mutant patients,
      EGFR-TKIs therapy produced a prominent PFS benefit in all settings. Among EGFR
      wild-type patients, EGFR-TKIs were inferior to chemotherapy both for first-line
      treatment and for second/third-line treatment. However, EGFR-TKIs maintenance and
      addition of EGFR-TKIs to chemotherapy could provide additive benefit over
      chemotherapy alone in such EGFR wild-type patients.

PMID- 26206592
TI  - Conifer genomics and adaptation: at the crossroads of genetic diversity and
      genome function.
AB  - Conifers have been understudied at the genomic level despite their worldwide
      ecological and economic importance but the situation is rapidly changing with the
      development of next generation sequencing (NGS) technologies. With NGS, genomics
      research has simultaneously gained in speed, magnitude and scope. In just a few
      years, genomes of 20-24 gigabases have been sequenced for several conifers, with
      several others expected in the near future. Biological insights have resulted
      from recent sequencing initiatives as well as genetic mapping, gene expression
      profiling and gene discovery research over nearly two decades. We review the
      knowledge arising from conifer genomics research emphasizing genome evolution and
      the genomic basis of adaptation, and outline emerging questions and knowledge
      gaps. We discuss future directions in three areas with potential inputs from NGS
      technologies: the evolutionary impacts of adaptation in conifers based on the
      adaptation-by-speciation model; the contributions of genetic variability of gene
      expression in adaptation; and the development of a broader understanding of
      genetic diversity and its impacts on genome function. These research directions
      promise to sustain research aimed at addressing the emerging challenges of
      adaptation that face conifer trees.

PMID- 26206593
TI  - Emerging role of doxycycline in vector-borne diseases.

PMID- 26206594
TI  - Dispatcher instruction of chest compression-only CPR increases actual provision
      of bystander CPR.
AB  - BACKGROUND: A preceding randomized controlled trial demonstrated that chest
      compression-only cardiopulmonary resuscitation (CPR) instruction by dispatcher
      was more effective to increase bystander CPR than conventional CPR instruction.
      However, the actual condition of implementation of each type of dispatcher
      instruction (chest compression-only CPR [CCCPR] or conventional CPR with rescue
      breathing) and provision of bystander CPR in real prehospital settings has not
      been sufficiently investigated. METHODS: This registry prospectively enrolled
      patients aged =>18 years suffering an out-of-hospital cardiac arrest (OHCA) of
      non-traumatic causes before emergency-medical-service (EMS) arrival, who were
      considered as target subjects of dispatcher instruction, resuscitated by EMS
      personnel, and transported to medical institutions in Osaka, Japan from January
      2005 through December 2012. The primary outcome measure was provision of CPR by a
      bystander. Multiple logistic regression analysis was used to assess factors that
      were potentially associated with provision of bystander CPR. RESULTS: Among
      37,283 target subjects of dispatcher instruction, 5743 received CCCPR instruction
      and 13,926 received conventional CPR instruction. The proportion of CCCPR
      instruction increased from 5.7% in 2005 to 25.6% in 2012 (p for trend <0.001).
      The CCCPR instruction group received bystander CPR more frequently than
      conventional CPR instruction group (70.0% versus 62.1%, p<0.001). In the
      multivariable analysis, CCCPR dispatcher instruction was significantly associated
      with provision of bystander CPR compared with conventional CPR instruction
      (adjusted odds ratio 1.44, 95% CI 1.34-1.55). CONCLUSIONS: CCCPR dispatcher
      instruction among adult OHCA patients significantly increased the actual
      provision of bystander CPR.

PMID- 26206595
TI  - Repeated diffusion weighted imaging in comatose cardiac arrest patients with
      therapeutic hypothermia.
AB  - BACKGROUND: The aim of this study was to evaluate the changing pattern and
      prognostic values of diffusion-weighted imaging (DWI) at two time points in
      cardiac arrest patients treated with therapeutic hypothermia. METHODS: Twenty two
      patients with cardiac arrest who underwent two DWI studies were enrolled in the
      retrospective study. The first DWI was performed after the induction of
      therapeutic hypothermia (median 6.0h) and was repeated between 48h and 168h
      (second DWI, median 74h). Apparent diffusion coefficient (ADC) values were
      measured in the predefined brain regions, and qualitative analysis was also
      performed. Good neurologic outcomes were defined as Cerebral Performance Category
      (CPC) scores of 1 and 2. RESULTS: The ADC value tended to increase over time
      except the cortical regions of the poor outcome group (N=10). In the comparisons
      of receiver operating characteristic (ROC) curve to predict poor outcome using
      ADC value, postcentral cortex in the second DWI has a better association with
      neurological outcome (p=0.001, area under the curve (AUC)=0.996 for second DWI,
      AUC=0.571 for first DWI). In the same analysis using qualitative score,
      precentral cortex, postcentral cortex, parietal lobe, occipital lobe, caudate and
      putamen in the second DWI have a better association with neurological outcome.
      CONCLUSIONS: The changing pattern of ADC values after cardiac arrest is different
      according to anatomic region and neurologic status. The DWI after 48h has a
      better association with neurological outcome of cardiac arrest patients in both
      quantitative and qualitative analysis.

PMID- 26206596
TI  - Causes for the declining proportion of ventricular fibrillation in out-of
      hospital cardiac arrest.
AB  - AIMS: The reported proportion of ventricular fibrillation (VF) in out-of-hospital
      cardiac arrest (OHCA) has declined worldwide. VF decline may be caused by less VF
      at collapse and/or faster dissolution of VF into asystole. We aimed to determine
      the causes of VF decline by comparing VF proportions in relation to delay from
      emergency medical services (EMS) call to initial ECG (call-to-ECG delay), and VF
      dissolution rates between two study periods. METHODS: Data from the AmsteRdam
      REsuscitation STudies (ARREST), an ongoing OHCA registry in the Netherlands, were
      used. We studied cardiac OHCA in the study periods 1995-1997 (n=917) and 2006
      2012 (n=5695). Cases with available ECG and information on call-to-ECG delay were
      included. We tested whether initial VF proportion and VF dissolution rates
      differed between both study periods using logistic regression. RESULTS: Despite a
      15% VF decline between the periods, VF proportion around EMS call remained high
      in 2006-2012 (64%). The odds ratio (OR) for VF proportion in 2006-2012 vs. 1995
      1997 was 0.52 (95%-CI 0.45-0.60, P<0.001), with similar rates of VF dissolution
      in both periods (P=0.83). VF decline was higher for unwitnessed collapse (OR
      0.41, 95%-CI 0.28-0.58) and collapse at home (OR 0.50, 95%-CI 0.42-0.59), but not
      for categories of bystander CPR, age or sex. CONCLUSION: VF proportion early
      after collapse remains high. VF decline is explained by the occurrence of less
      initial VF, rather than faster dissolving VF. An increase in unwitnessed OHCA and
      collapse at home contributes to the observed VF decline.

PMID- 26206597
TI  - Observational study of children admitted to United Kingdom and Republic of
      Ireland Paediatric Intensive Care Units after out-of-hospital cardiac arrest.
AB  - AIMS: To estimate the prevalence of children admitted after out-of-hospital
      cardiac arrest (OHCA) to UK and Republic of Ireland (RoI) Paediatric Intensive
      Care Units (PICUs) and factors associated with mortality to inform future
      clinical trial feasibility. METHOD: Observational study using a prospectively
      collected dataset of the Paediatric Intensive Care Audit Network (PICANet) of 33
      UK and RoI PICUs (January 2003 to June 2010). Cases (0 to <16 years), with
      documented OHCA surviving to PICU admission and requiring mechanical ventilation
      were included. Main outcomes were prevalence for admission and death within PICU.
      Factors associated with mortality were examined with multiple logistic regression
      analysis. RESULTS: 827 of 111,170 admissions (0.73%; 95% CI [0.48 to 0.98%]) were
      identified as children admitted following OHCA. PICU mortality for OHCA was 50.5%
      (418/827). Recruitment into an adequately sized clinical trial would not be
      feasible with the current prevalence rate. Characteristics at PICU admission
      associated with increased risk of death included; bilateral unreactive pupils,
      genetically inherited condition, inter-hospital transfer to PICU, requirement for
      vasoactive drugs and greater base deficit. Factors associated with reduced risk
      of death were submersion or a respiratory aetiology and pre-existing respiratory
      or cardiac conditions. CONCLUSIONS: Less than 120 children a year are admitted to
      PICUs in the UK and RoI after OHCA, limiting options for conducting UK
      intervention trials. The risk factors associated with mortality identified in
      this study will allow risk stratification in future studies.

PMID- 26206598
TI  - Renal Embolization and Urothelial Sclerotherapy for Recurrent Obstructive
      Urosepsis and Intractable Haematuria from Upper Tract Urothelial Carcinoma.
AB  - Management of intractable haematuria and obstructive urosepsis from upper tract
      urothelial carcinoma can be problematic in patients not suitable for surgery,
      chemotherapy or radiotherapy. Interventional radiology techniques provide
      alternative approaches in this setting, such as complete kidney embolization to
      cease urine output, percutaneous nephrostomy, antegrade injection of
      sclerotherapy agents and sterilisation of the upper collecting system. Related
      approaches have been successfully employed to sclerose renal cysts, lymphoceles,
      chyluria and intractable lower tract haemorrhage. No reports of percutaneous,
      antegrade sclerotherapy in the upper urinary tract have previously been
      published. We present a case of recurrent haematuria and obstructive urosepsis
      caused by invasive upper tract urothelial carcinoma in a non-operative patient,
      which was treated with renal embolisation and percutaneous upper tract urothelial
      sclerotherapy. 

PMID- 26206599
TI  - Chaperone-mediated autophagy: roles in neuroprotection.
AB  - Chaperone-mediated autophagy (CMA), one of the main pathways of lysosomal
      proteolysis, is characterized by the selective targeting and direct translocation
      into the lysosomal lumen of substrate proteins containing a targeting motif
      biochemically related to the pentapeptide KFERQ. Along with the other two
      lysosomal pathways, macro- and micro-autophagy, CMA is essential for maintaining
      cellular homeostasis and survival by selectively degrading misfolded, oxidized,
      or damaged cytosolic proteins. CMA plays an important role in pathologies such as
      cancer, kidney disorders, and neurodegenerative diseases. Neurons are post
      mitotic and highly susceptible to dysfunction of cellular quality-control
      systems. Maintaining a balance between protein synthesis and degradation is
      critical for neuronal functions and homeostasis. Recent studies have revealed
      several new mechanisms by which CMA protects neurons through regulating factors
      critical for their viability and homeostasis. In the current review, we summarize
      recent advances in the understanding of the regulation and physiology of CMA with
      a specific focus on its possible roles in neuroprotection.

PMID- 26206601
TI  - 210th ENMC International Workshop: Research and clinical management of patients
      with spinal and bulbar muscular atrophy, 27-29 March, 2015, Naarden, The
      Netherlands.

PMID- 26206600
TI  - Chaperone-mediated autophagy and neurodegeneration: connections, mechanisms, and
      therapeutic implications.
AB  - Lysosomes degrade dysfunctional intracellular components via three pathways:
      macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Unlike
      the other two, CMA degrades cytosolic proteins with a recognized KFERQ-like motif
      in lysosomes and is important for cellular homeostasis. CMA activity declines
      with age and is altered in neurodegenerative diseases. Its impairment leads to
      the accumulation of aggregated proteins, some of which may be directly tied to
      the pathogenic processes of neurodegenerative diseases. Its induction may
      accelerate the clearance of pathogenic proteins and promote cell survival,
      representing a potential therapeutic approach for the treatment of
      neurodegenerative diseases. In this review, we summarize the current findings on
      how CMA is involved in neurodegenerative diseases, especially in Parkinson's
      disease. 

PMID- 26206602
TI  - Resuscitative thoracotomy for pediatric trauma in Illinois, 1999 to 2009.
AB  - BACKGROUND: Outcomes in adults who undergo resuscitative thoracotomy are poor.
      Few studies have examined the procedure's use in pediatric trauma. METHODS: The
      Illinois State Trauma Registry was queried for thoracotomy performed in the
      emergency department from 1999 to 2009, for patients aged 0 to 15. Injury
      mechanism, vital signs, and mortality were examined while controlling for injury
      severity. RESULTS: Resuscitative thoracotomy was infrequently performed in
      pediatric trauma (n = 25; 2.3/year). Most patients had suffered penetrating
      injury. Patients who underwent resuscitative thoracotomy were in extremis, with
      only 17% demonstrating signs of life upon presentation. Although 6 patients (24%)
      survived initially, only 2 (8%) survived to hospital discharge. CONCLUSIONS:
      Resuscitative thoracotomy was rarely performed in children in Illinois emergency
      departments. Survival is low for thoracotomy in the emergency department, but
      some patients who presented with penetrating injuries did have positive outcomes,
      supporting a continued role for the procedure in select cases.

PMID- 26206603
TI  - BDE-209 inhibits pluripotent genes expression and induces apoptosis in human
      embryonic stem cells.
AB  - Decabromodiphenyl ether (BDE-209) has been detected in human serum, semen,
      placenta, cord blood and milk worldwide. However, little is known regarding the
      potential effects on the early human embryonic development of BDE-209. In this
      study, human embryonic stem cell lines FY-hES-10 and FY-hES-26 were used to
      evaluate the potential effects and explore the toxification mechanisms using low
      level BDE-209 exposure. Our data showed that BDE-209 exposure (1, 10 and 100 nM)
      reduced the expression of pluripotent genes such as OCT4, SOX2 and NANOG and
      induced human embryonic stem cells (hESCs) apoptosis. The downregulation of
      BIRC5/BCL2 and upregulation of BAX were related to apoptosis of hESCs induced by
      BDE-209 exposure. A mechanism study showed that OCT4 down-regulation accompanied
      by OCT4 promoter hypermethylation and increasing miR-145/miR-335 levels, OCT4
      inhibitors. Moreover, BDE-209 could increase the generation of intracellular
      reactive oxygen species (ROS) and decrease SOD2 expression. The ROS increase and
      OCT4 downregulation after BDE-209 exposure could be reversed partly by
      antioxidant N-acetylcysteine supplement. These findings showed that BDE-209
      exposure could decrease pluripotent genes expression via epigenetic regulation
      and induce apoptosis through ROS generation in human embryonic stem cells in
      vitro.

PMID- 26206604
TI  - A new quantitative method for evaluating freezing of gait and dual-attention task
      deficits in Parkinson's disease.
AB  - People with Parkinson's disease (PD) can exhibit disabling gait symptoms such as
      freezing of gait especially when distracted by a secondary task. Quantitative
      measurement method of this type of cognitive-motor abnormality, however, remains
      poorly developed. Here we examined whether stepping-in-place (SIP) with a
      concurrent mental task (e.g., subtraction) can be used as a simple method for
      evaluating cognitive-motor deficits in PD. We used a 4th generation iPod Touch
      sensor system to capture hip flexion data and obtain step height (SH)
      measurements (z axis). The accuracy of the method was compared to and validated
      by kinematic video analysis software. We found a general trend of reduced SH for
      PD subjects relative to controls under all conditions. However, the SH of PD
      freezers was significantly worse than PD non-freezers and controls during
      concurrent serial 7 subtraction and SIP tasking. During serial 7 subtraction, SH
      was significantly associated with whether or not a PD patient was a self-reported
      freezer even when controlling for disease severity. Given that this SIP-based
      dual-task paradigm is not limited by space requirements and can be quantified
      using a mobile tracking device that delivers specifically designed auditory task
      instructions, the method reported here may be used to standardize clinical
      assessment of cognitive-motor deficits under a variety of dual-task conditions in
      PD. 

PMID- 26206605
TI  - Sustained attention in adult ADHD: time-on-task effects of various measures of
      attention.
AB  - Neuropsychological research on adults with ADHD showed deficits in various
      aspects of attention. However, the majority of studies failed to explore the
      change of performance over time, so-called time-on-task effects. As a
      consequence, little is known about sustained attention performance of adults with
      ADHD. The aim of the present study was therefore to test the hypothesis of
      sustained attention deficits of adults with ADHD. Twenty-nine adults with ADHD
      and 30 healthy individuals were assessed on four 20-min tests of sustained
      attention, measuring alertness, selective attention, divided attention and
      flexibility. The deterioration of performance over time (time-on-task effects)
      was compared between patients with ADHD and healthy individuals to conclude on
      sustained attention performance. Compared to healthy individuals, patients with
      ADHD showed significant deficits of medium size in selective attention and
      divided attention. Furthermore, medium sustained attention deficits was observed
      in measures of alertness, selective attention and divided attention. This study
      supports the notion of sustained attention deficits of adults with ADHD.

PMID- 26206606
TI  - Echinococcus multilocularis detection in the intestines and feces of free-ranging
      domestic cats (Felis s. catus) and European wildcats (Felis s. silvestris) from
      northeastern France.
AB  - Experimental studies have demonstrated that cats can be infected by Echinococcus
      multilocularis, although few data are available concerning their natural
      infection. This study was designed to compare experimental findings with
      information on the prevalence of natural E. multilocularis infections of cats in
      a rural high endemic area. Of 19 intestines of domestic cats (Felis s. catus) and
      five of European wildcats (Felis s. silvestris) analyzed by segmental
      sedimentation and counting technique (SSCT), infection by E. multilocularis was
      observed for one individual of each species, resulting in a prevalence estimated
      at 5%, (CI95%: 1-26) in domestic cats and at 20% (CI95%: 1-72) in wildcats. High
      worm burdens (680 and 7040) were noted, but comprised only immature worms. The
      same EmsB microsatellite profile obtained from the worms' DNA was observed in the
      two cats as in foxes from the same area and from other European countries. The
      presence of E. multilocularis DNA was diagnosed in 3.1% (10/321) of the domestic
      cat feces collected on the field in two villages. However, no E. multilocularis
      eggs were found after flotation with zinc chloride of the positive feces. The
      detection of DNA from E. multilocularis was thought to be due to the presence of
      cells from worms untied from the intestine and corresponding to prepatent
      infection or due to the digested metacestode. These results from E.
      multilocularis presence in wild and domestic cat populations agree with those
      previously obtained by experimental infections. These findings support that these
      cats play an insignificant role in E. multilocularis transmission, even in a
      "highly endemic" region. Nevertheless, since the presence of thick-shelled E.
      multilocularis eggs from cats has already been reported, the associated zoonotic
      risk cannot be totally ruled out, even if it is very low. 

PMID- 26206607
TI  - Laboratory evaluation of a native strain of Beauveria bassiana for controlling
      Dermanyssus gallinae (De Geer, 1778) (Acari: Dermanyssidae).
AB  - The poultry red mite, Dermanyssus gallinae (De Geer, 1778) (Acari: Dermanyssidae)
      is one of the most economically important ectoparasites of laying hens worldwide.
      Chemical control of this mite may result in environmental and food contamination,
      as well as the development of drug resistance. High virulence of Beauveria
      bassiana sensu lato strains isolated from naturally infected hosts or from their
      environment has been demonstrated toward many arthropod species, including ticks.
      However, a limited number of studies have assessed the use of B. bassiana for the
      control of D. gallinae s.l. and none of them have employed native strains. This
      study reports the pathogenicity of a native strain of B. bassiana (CD1123)
      against nymphs and adults of D. gallinae. Batches of nymph and adult mites (i.e.,
      n=720 for each stage) for treated groups (TGs) were placed on paper soaked with a
      0.1% tween 80 suspension of B. bassiana (CIS, 10(5), 10(7) and 10(9) conidia/ml),
      whilst 240 untreated control mites for each stage (CG) were exposed only to 0.1%
      tween 80. The mites in TG showed a higher mortality at all stages (p<0.01) when
      compared to CG, depending on the time of exposure and the conidial concentration.
      A 100% mortality rate was recorded using a CIS of 10(9) conidia/ml 12 days post
      infection (DPI) in adults and 14 DPI in nymphs. B. bassiana suspension containing
      10(9) conidia/ml was highly virulent towards nymph and adult stages of D.
      gallinae, therefore representing a possible promising natural product to be used
      in alternative or in combination to other acaricidal compounds currently used for
      controlling the red mite. 

PMID- 26206608
TI  - Expression of virus-responsive genes and their response to challenge with
      poly(I:C) at different stages of the annual fish Nothobranchius guentheri:
      Implications for an asymmetric decrease in immunity.
AB  - Aging deteriorates immunity. However, if aging affects immunity in an asymmetric
      or symmetric way remains largely unknown. In this study we clearly demonstrate
      that compared with adult fish, the anti-viral responses of aged annual fish
      Nothobranchius guentheri, as reflected by the expression levels of virus
      responsive genes, including lgp2 and mda5 encoding sensor molecules, ifn-i and
      viperin encoding the effector molecules and irf1, irf7, stat1 and atf3 encoding
      the regulation elements, are either reduced remarkably or elevated markedly or
      show little difference depending upon the different tissues. Moreover, although
      challenge with poly(I:C) results in a significant decrease in the expression of
      virus-responsive genes in most tissues of aged N. guentheri, it also causes a
      considerable increase in the expression of the genes in other tissues of aged
      fish. Collectively, these data suggest that the anti-viral responses of the
      annual fish N. guentheri generally reduces with age in an asymmetric way among
      the most tissues.

PMID- 26206609
TI  - Three members in JAK/STAT signal pathway from the sea cucumber Apostichopus
      japonicus: Molecular cloning, characterization and function analysis.
AB  - The JAK/STAT signal transduction pathway plays a critical role in host defense
      against bacterial infections. In the present study, we firstly cloned the full
      length cDNAs of three molecules in JAK/STAT cascade, STAT5, FOXP and SOCS2, from
      sea cucumber Apostichopus japonicus (denoted as AjSTAT5, AjFOXP, AjSOCS2,
      respectively) and investigated their immune functions towards Vibrio splendidus
      infection and LPS exposure. The AjSTAT5 cDNA was composed of 2643 bp consisting
      of 787 amino acid residues which included protein interaction domain, STAT-alpha
      domain, DNA binding domain and SH2 domain. The putative AjFOXP contained a
      ZnF_C2H2 domain, the leucine zipper-like domain and FH domain, all of which were
      thought to be the representative characteristics of FOXP subfamily. The deduced
      amino acids sequence of AjSOCS2 included an SH2 domain and SOCS box domain
      similar to vertebrate SOCS counterparts. Phylogenetic trees further supported
      that all these three identified proteins belonged to novel members of JAK/STAT
      signal pathway in sea cucumber. Tissue specific expression analysis showed that
      three genes were ubiquitously expressed in all examined tissues. AjSTAT5 and
      AjFOXP were both dominantly expressed in intestine, tentacle and respiratory
      tree, and weak in muscle. In contrary, the peak expression of AjSOCS2 was
      observed in muscle and lowest in respiratory tree. The V. splendidus challenge
      and LPS exposure could both significantly up-regulate the mRNA expression of
      three genes, in which AjSOCS2 showed opposite expression trends to those of
      AjSTAT5 and AjFOXP. Silencing the AjSTAT5 by siRNA depressed the AjFOXP
      expression, but induced the expression level of AjSOCS2, revealing that AjSTAT5
      might directly modulate AjFOXP, and AjSOCS2 function primarily by acting as a
      potent inhibitor involve in JAK/STAT pathway. The present study would expand our
      understanding on JAK/STAT signaling transduction pathway in modulating the innate
      immune responses of sea cucumber.

PMID- 26206610
TI  - Winter eruption on the thighs.

PMID- 26206611
TI  - Health-Related Quality of Life and Pain Intensity Among Ethnically Diverse
      Community-Dwelling Older Adults.
AB  - Chronic pain is highly prevalent in older adults and often negatively associated
      with health-related quality of life (HRQoL). This study compared HRQoL, including
      physical health and mental health, in persons of differing ethnicities, and
      identified factors associated with pain intensity and HRQoL in ethnically diverse
      older adults. Older adults with chronic pain from four ethnic groups (African
      Americans, Afro-Caribbeans, Hispanics, and European Americans) were recruited
      from the Florida Atlantic University Healthy Aging Research Initiative (HARI)
      registry. The Medical Outcomes Study Short Form-36 (SF-36) was used to evaluate
      HRQoL, including functional status, emotional well-being, and social functioning.
      Of 593 persons in the four ethnic groups in the registry, 174 met the inclusion
      criteria (pain level of four or higher on an 11-point scale, lasting 3 months or
      longer). Among these 174, African Americans reported the highest level of pain
      intensity, followed by Afro-Caribbeans, Hispanics, and European Americans.
      Hispanics reported the highest physical health scores and the lowest mental
      health scores. In contrast, African Americans reported the highest mental health
      scores and the lowest physical health scores. Multivariate linear regression
      analysis revealed that ethnicity, lower physical health scores, and lower mental
      health scores were significantly (p <= .01) associated with pain intensity.
      Understanding ethnic variations in response to pain intensity may address gaps in
      knowledge about HRQoL to reduce disparities in optimal care. Health care
      providers should consider ethnic norms and cultural diversity to provide optimal
      interventions for this population. 

PMID- 26206612
TI  - Reduction of Cullin-2 in somatic cells disrupts differentiation of germline stem
      cells in the Drosophila ovary.
AB  - Signaling from a niche consisting of somatic cells is essential for maintenance
      of germline stem cells (GSCs) in the ovary of Drosophila. Decapentaplegic (Dpp),
      a type of bone morphogenetic protein (BMP) signal, emanating from the niche, is
      the most important signal for this process. Cullin proteins constitute the core
      of a multiprotein E3-ligase important for their functions viz. degradation or
      modification of proteins necessary for different cellular processes. We have
      found that a Cullin protein called Cullin-2 (Cul-2) expresses in both somatic and
      germline cells of the Drosophila ovary. Reduction of Cul-2 in somatic cells
      causes upregulation of Dpp signal and produces accumulation of extra GSC-like
      cells inside germarium, the anteriormost structure of the ovary. Our results
      suggest that Cullin-2 protein present in the somatic cells is involved in a non
      cell-autonomous regulation of the extent of Dpp signaling and thus controls the
      differentiation of GSCs to cystoblasts (CBs). 

PMID- 26206613
TI  - Evolution of the chordate regeneration blastema: Differential gene expression and
      conserved role of notch signaling during siphon regeneration in the ascidian
      Ciona.
AB  - The regeneration of the oral siphon (OS) and other distal structures in the
      ascidian Ciona intestinalis occurs by epimorphosis involving the formation of a
      blastema of proliferating cells. Despite the longstanding use of Ciona as a model
      in molecular developmental biology, regeneration in this system has not been
      previously explored by molecular analysis. Here we have employed microarray
      analysis and quantitative real time RT-PCR to identify genes with differential
      expression profiles during OS regeneration. The majority of differentially
      expressed genes were downregulated during OS regeneration, suggesting roles in
      normal growth and homeostasis. However, a subset of differentially expressed
      genes was upregulated in the regenerating OS, suggesting functional roles during
      regeneration. Among the upregulated genes were key members of the Notch signaling
      pathway, including those encoding the delta and jagged ligands, two fringe
      modulators, and to a lesser extent the notch receptor. In situ hybridization
      showed a complementary pattern of delta1 and notch gene expression in the
      blastema of the regenerating OS. Chemical inhibition of the Notch signaling
      pathway reduced the levels of cell proliferation in the branchial sac, a stem
      cell niche that contributes progenitor cells to the regenerating OS, and in the
      OS regeneration blastema, where siphon muscle fibers eventually re-differentiate.
      Chemical inhibition also prevented the replacement of oral siphon pigment organs,
      sensory receptors rimming the entrance of the OS, and siphon muscle fibers, but
      had no effects on the formation of the wound epidermis. Since Notch signaling is
      involved in the maintenance of proliferative activity in both the Ciona and
      vertebrate regeneration blastema, the results suggest a conserved evolutionary
      role of this signaling pathway in chordate regeneration. The genes identified in
      this investigation provide the foundation for future molecular analysis of OS
      regeneration. 

PMID- 26206614
TI  - ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the
      homophilic binding site.
AB  - The cranial neural crest (CNC) is a highly motile population of cells that is
      responsible for forming the face and jaw in all vertebrates and perturbing their
      migration can lead to craniofacial birth defects. Cell motility requires a
      dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage
      of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell
      migration. This cleavage generates a shed extracellular fragment of cadherin-11
      (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin
      11 plays an important role in modulating contact inhibition of locomotion (CIL)
      in the CNC to regulate directional cell migration. Here, we show that while the
      integral cadherin-11 requires the homophilic binding site to promote CNC
      migration in vivo, the EC1-3 fragment does not. In addition, we show that
      increased ADAM13 activity or expression of the EC1-3 fragment increases CNC
      invasiveness in vitro and blocks the repulsive CIL response in colliding cells.
      This activity requires the presence of an intact homophilic binding site on the
      EC1-3 suggesting that the cleavage fragment may function as a competitive
      inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in
      vivo.

PMID- 26206616
TI  - Stratospheric Ozone destruction by the Bronze-Age Minoan eruption (Santorini
      Volcano, Greece).
AB  - The role of volcanogenic halogen-bearing (i.e. chlorine and bromine) compounds in
      stratospheric ozone chemistry and climate forcing is poorly constrained. While
      the 1991 eruption of Pinatubo resulted in stratospheric ozone loss, it was due to
      heterogeneous chemistry on volcanic sulfate aerosols involving chlorine of
      anthropogenic rather than volcanogenic origin, since co-erupted chlorine was
      scavenged within the plume. Therefore, it is not known what effect volcanism had
      on ozone in pre-industrial times, nor what will be its role on future atmospheres
      with reduced anthropogenic halogens present. By combining petrologic constraints
      on eruption volatile yields with a global atmospheric chemistry-transport model,
      we show here that the Bronze-Age 'Minoan' eruption of Santorini Volcano released
      far more halogens than sulfur and that, even if only 2% of these halogens reached
      the stratosphere, it would have resulted in strong global ozone depletion. The
      model predicts reductions in ozone columns of 20 to >90% at Northern high
      latitudes and an ozone recovery taking up to a decade. Our findings emphasise the
      significance of volcanic halogens for stratosphere chemistry and suggest that
      modelling of past and future volcanic impacts on Earth's ozone, climate and
      ecosystems should systematically consider volcanic halogen emissions in addition
      to sulfur emissions. 

PMID- 26206617
TI  - Is the surface oxygen exchange rate linked to bulk ion diffusivity in mixed
      conducting Ruddlesden-Popper phases?
AB  - The possible link between oxygen surface exchange rate and bulk oxygen anion
      diffusivity in mixed ionic and electronic conducting oxides is a topic of great
      interest and debate. While a large body of experimental evidence and theoretical
      analyses support a link, observed differences between bulk and surface
      composition of these materials are hard to reconcile with this observation. This
      is further compounded by potential problems with simultaneous measurement of both
      parameters. Here we utilize separate techniques, in situ neutron diffraction and
      pulsed isotopic surface exchange, to examine bulk ion mobility and surface oxygen
      exchange rates of three Ruddlesden-Popper phases, general form A(n
      1)A(2)'B(n)O(3n+1), A(n-1)A(2)'B(n)X(3n+1); LaSrCo(0.5)Fe(0.5)O(4-delta) (n = 1),
      La(0.3)Sr(2.7)CoFeO(7-delta) (n = 2) and LaSr3Co(1.5)Fe(1.5)O(10-delta) (n = 3).
      These measurements are complemented by surface composition determination via high
      sensitivity-low energy ion scattering. We observe a correlation between bulk ion
      mobility and surface exchange rate between materials. The surface exchange rates
      vary by more than one order of magnitude with high anion mobility in the bulk of
      an oxygen vacancy-rich n = 2 Ruddlesden-Popper material correlating with rapid
      oxygen exchange. This is in contrast with the similar surface exchange rates
      which we may expect due to similar surface compositions across all three samples.
      We conclude that experimental limitations lead to inherent convolution of surface
      and bulk rates, and that surface exchange steps are not likely to be rate
      limiting in oxygen incorporation.

PMID- 26206615
TI  - The Hox gene Dfd controls organogenesis by shaping territorial border through
      regulation of basal DE-Cadherin distribution.
AB  - Hox genes are highly conserved selector genes controlling tissue identity and
      organogenesis. Recent work indicates that Hox genes also controls cell
      segregation and segmental boundary in various species, however the underlying
      cellular mechanisms involved in this function are poorly understood. In
      Drosophila melanogaster, the Hox gene Deformed (Dfd) is required for
      specification and organogenesis of the adult Maxillary (Mx) palp. Here, we
      demonstrate that differential Dfd expression control Mx morphogenesis through the
      formation of a physical boundary separating the Mx field and the Peripodial
      Epithelium (PE). We show that this boundary relies on DE-cadherin (DE-cad) basal
      accumulation in Mx cells controlled by differential Dfd expression. Indeed, Dfd
      controls boundary formation through cell autonomous basal redistribution of DE
      cad which leads to subsequent fold at the Dfd expression border. Finally, the
      loss of Mx DE-cad basal accumulation and hence of Mx-PE folding is sufficient to
      prevent Mx organogenesis thus revealing the crucial role of boundaries in organ
      differentiation. Altogether, these results reveal that Hox coordination of tissue
      morphogenesis relies on boundary fold formation through the modulation of DE-cad
      positioning. 

PMID- 26206618
TI  - Distinguishing the status of human herpesvirus 6 and 7 infection.

PMID- 26206619
TI  - Treatment options for dyslipidemia in chronic kidney disease and for protection
      from contrast-induced nephropathy.
AB  - Chronic kidney disease (CKD) is highly prevalent worldwide and represents a major
      cardiovascular risk factor. Dyslipidemia is present in most patients with CKD and
      further worsens CKD, creating a vicious cycle. The treatment of CKD-related
      dyslipidemia has been a controversial topic. The use of statins is recommended in
      all stages of CKD, but it appears to reduce cardiovascular and renal events only
      in the early CKD stages, up to stage 3. The use of atorvastatin has proven very
      beneficial; thus, the earliest we start statin treatment, the better for the
      patient. Atorvastatin and pitavastatin do not need dose adjustments at any level
      of renal function. Fibrates can be administered in mixed hyperlipidemia, combined
      with statins in early CKD stages. Omega-3 fatty acids are useful for treating
      hypertriglyceridemia in CKD. Antibodies against proprotein convertase
      subtilisin/kexin type 9 hold promise for a better control of dyslipidemia and a
      greater reduction of cardiovascular risk. 

PMID- 26206620
TI  - The Role of Casein Kinase 2 in Ion Channel Remodeling After Myocardial
      Infarction. Editorial to: "Valsartan Upregulates Kir2.1 in Rats Suffering from
      Myocardial Infarction via Casein Kinase 2" by Xinran Li et al.

PMID- 26206621
TI  - Weight-based antibiotic dosing in a real-world European study of complicated skin
      and soft-tissue infections due to methicillin-resistant Staphylococcus aureus.
AB  - We aimed to characterize real-world dosing of weight-based intravenous (IV)
      antibiotic therapy in patients hospitalized for methicillin-resistant
      Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections
      (cSSTIs). This was a subgroup analysis of a retrospective chart review that
      captured data from 12 European countries. The study included patients >=18 years
      old, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and
      discharged alive by 31 July 2011. Patients treated with IV vancomycin,
      teicoplanin or daptomycin at any stage during hospitalization were included in
      this analysis. Analyses were conducted at the regimen level (dosing in mg/kg or
      in mg, frequency, and total daily dose (TDD)), with potentially multiple regimens
      per patient, and the patient level, categorizing patients into low, standard
      (labelled) and high dosing groups according to their initial MRSA-targeted
      regimen. Among the 1502 patients in the parent study, 998 patients contributed a
      total of 1050 daptomycin, teicoplanin or vancomycin regimens. Across all
      regimens, the mean initial TDDs were 6.3 +/- 1.9 mg/kg for daptomycin, 10.5 +/-
      4.9 mg/kg for teicoplanin and 28.5 +/- 11.5 mg/kg for vancomycin. A total of 789
      patients received first-line therapy with one of the above antibiotics. The
      majority of patients receiving first-line teicoplanin and daptomycin (96% and
      80%, respectively) received higher than labelled cSSTI doses, whereas vancomycin
      doses were lower than labelled doses in >40% of patients. These real-world data
      reveal significant deviation from labelled antibiotic dosing in 12 European
      countries and the potential for suboptimal outcomes in patients with MRSA cSSTIs.

PMID- 26206622
TI  - Navigating environmental, economic, and technological trade-offs in the design
      and operation of submerged anaerobic membrane bioreactors (AnMBRs).
AB  - Anaerobic membrane bioreactors (AnMBRs) enable energy recovery from wastewater
      while simultaneously achieving high levels of treatment. The objective of this
      study was to elucidate how detailed design and operational decisions of submerged
      AnMBRs influence the technological, environmental, and economic sustainability of
      the system across its life cycle. Specific design and operational decisions
      evaluated included: solids retention time (SRT), mixed liquor suspended solids
      (MLSS) concentration, sludge recycling ratio (r), flux (J), and specific gas
      demand per membrane area (SGD). The possibility of methane recovery (both as
      biogas and as soluble methane in reactor effluent) and bioenergy production,
      nutrient recovery, and final destination of the sludge (land application,
      landfill, or incineration) were also evaluated. The implications of these design
      and operational decisions were characterized by leveraging a quantitative
      sustainable design (QSD) framework which integrated steady-state performance
      modeling across seasonal temperatures (using pilot-scale experimental data and
      the simulating software DESASS), life cycle cost (LCC) analysis, and life cycle
      assessment (LCA). Sensitivity and uncertainty analyses were used to characterize
      the relative importance of individual design decisions, and to navigate trade
      offs across environmental, economic, and technological criteria. Based on this
      analysis, there are design and operational conditions under which submerged
      AnMBRs could be net energy positive and contribute to the pursuit of carbon
      negative wastewater treatment. 

PMID- 26206624
TI  - PROCEEDINGS FROM THE 22ND CONGRESS OF THE WORLD ASSOCIATION FOR SEXUAL HEALTH,
      SINGAPORE, JULY 25-28, 2015.

PMID- 26206623
TI  - Message from WAS Scientific Committee, Local Scientific Committee, the WAS and
      Congress Presidents.

PMID- 26206625
TI  - Round robin test on quantification of amyloid-beta 1-42 in cerebrospinal fluid by
      mass spectrometry.
AB  - INTRODUCTION: Cerebrospinal fluid (CSF) amyloid-beta 1-42 (Abeta42) is an
      important biomarker for Alzheimer's disease, both in diagnostics and to monitor
      disease-modifying therapies. However, there is a great need for standardization
      of methods used for quantification. To overcome problems associated with
      immunoassays, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has
      emerged as a critical orthogonal alternative. METHODS: We compared results for
      CSF Abeta42 quantification in a round robin study performed in four laboratories
      using similar sample preparation methods and LC-MS instrumentation. RESULTS: The
      LC-MS results showed excellent correlation between laboratories (r(2) >0.98),
      high analytical precision, and good correlation with enzyme-linked immunosorbent
      assay (r(2) >0.85). The use of a common reference sample further decreased
      interlaboratory variation. DISCUSSION: Our results indicate that LC-MS is
      suitable for absolute quantification of Abeta42 in CSF and highlight the
      importance of developing a certified reference material.

PMID- 26206626
TI  - Medical costs of Alzheimer's disease misdiagnosis among US Medicare
      beneficiaries.
AB  - INTRODUCTION: Recent developments in diagnostic technology can support earlier,
      more accurate diagnosis of non-Alzheimer's disease (AD) dementias. METHODS: To
      evaluate potential economic benefits of early rule-out of AD, annual medical
      resource use and costs for Medicare beneficiaries potentially misdiagnosed with
      AD prior to their diagnosis of vascular dementia (VD) or Parkinson's disease (PD)
      were compared with that of similar patients never diagnosed with AD. RESULTS:
      Patients with prior AD diagnosis used substantially more medical services every
      year until their VD/PD diagnosis, resulting in incremental annual medical costs
      of approximately $9,500-$14,000. However, following their corrected diagnosis,
      medical costs converged with those of patients never diagnosed with AD.
      DISCUSSION: The observed correlation between timing of correct diagnosis and
      subsequent reversal in excess costs is strongly suggestive of the role of
      misdiagnosis of AD - rather than AD comorbidity - in this patient population. Our
      findings suggest potential benefits from earlier, accurate diagnosis.

PMID- 26206627
TI  - A norepinephrine coated magnetic molecularly imprinted polymer for simultaneous
      multiple chiral recognition.
AB  - A newly designed molecularly imprinted polymer (MIP) material was developed and
      successfully used as recognition element for enantioselective recognition by
      microchip electrophoresis. In this work, molecularly imprinted polymers were
      facilely prepared employing Fe3O4 nanoparticles (NPs) as the supporting substrate
      and norepinephrine as the functional monomer in the presence of template molecule
      in a weak alkaline solution. After extracting the embedded template molecules,
      the produced imprinted Fe3O4@polynorepinephrine (MIP-Fe3O4@PNE) NPs have cavities
      complementary to three dimensional shape of template molecules favoring high
      binding capacity and magnetism property for easy manipulation. The MIP-Fe3O4@PNE
      NPs prepared with l-tryptophan, l-valine, l-threonine, Gly-l-Phe, S-(-)-ofloxacin
      or S-(-)-binaphthol as template molecules were packed in the polydimethylsiloxane
      microchannel via magnetic field as novel stationary phase to successful
      enantioseparation of corresponding target analysts. The MIP-Fe3O4@PNE NPs-based
      microchip electrophoresis system exhibited strong recognition ability, excellent
      high-performance, admirable reproducibility and stability, which provided a
      powerful protocol for separation enantiomers within a short analytical time and
      opened up an avenue for multiplex chiral compound assay in various systems. 

PMID- 26206628
TI  - Capillary ion chromatography with on-column focusing for ultra-trace analysis of
      methanesulfonate and inorganic anions in limited volume Antarctic ice core
      samples.
AB  - Preservation of ionic species within Antarctic ice yields a unique proxy record
      of the Earth's climate history. Studies have been focused until now on two
      proxies: the ionic components of sea salt aerosol and methanesulfonic acid.
      Measurement of the all of the major ionic species in ice core samples is
      typically carried out by ion chromatography. Former methods, whilst providing
      suitable detection limits, have been based upon off-column preconcentration
      techniques, requiring larger sample volumes, with potential for sample
      contamination and/or carryover. Here, a new capillary ion chromatography based
      analytical method has been developed for quantitative analysis of limited volume
      Antarctic ice core samples. The developed analytical protocol applies capillary
      ion chromatography (with suppressed conductivity detection) and direct on-column
      sample injection and focusing, thus eliminating the requirement for off-column
      sample preconcentration. This limits the total sample volume needed to 300MUL per
      analysis, allowing for triplicate sample analysis with <1mL of sample. This new
      approach provides a reliable and robust analytical method for the simultaneous
      determination of organic and inorganic anions, including fluoride,
      methanesulfonate, chloride, sulfate and nitrate anions. Application to composite
      ice-core samples is demonstrated, with coupling of the capillary ion
      chromatograph to high resolution mass spectrometry used to confirm the presence
      and purity of the observed methanesulfonate peak. 

PMID- 26206629
TI  - Surface charge fine tuning of reversed-phase/weak anion-exchange type mixed-mode
      stationary phases for milder elution conditions.
AB  - A series of new mixed-mode reversed-phase/weak anion-exchange (RP/WAX) phases
      have been synthesized by immobilization of N-undecenyl-3-alpha-aminotropane onto
      thiol-modified silica gel by thiol-ene click chemistry and subsequent
      introduction of acidic thiol-endcapping functionalities of different type and
      surface densities. Click chemistry allowed to adjust a controlled surface
      concentration of the RP/WAX ligand in such a way that a sufficient quantity of
      residual thiols remained unmodified which have been capped by thiol click with
      either 3-butenoic acid or allylsulfonic acid as co-ligands. In another
      embodiment, performic acid oxidation of N-undecenyl-3-alpha-aminotropane
      derivatized thiol-modified silica gave a RP/WAX phase with high density of
      sulfonic acid end-capping groups. zeta-Potential determinations confirmed the
      fine-tuned pI of these mixed-mode stationary phases which was shifted from 9.5 to
      8.2, 7.8, and 6.5 with 3-butenoic acid and allylsulfonic acid end-capping as well
      as performic acid oxidation. For acidic solutes, the co-ionic endcapping leads to
      strongly reduced retention times and clearly allowed elution of these analytes
      under lower ionic strength thus milder elution conditions. In spite of the acidic
      endcapping, the new mixed-mode phases maintained their hydrophobic and anion
      exchange selectivity as well as their multimodal nature featuring RP and HILIC
      elution domains at acetonitrile percentages below and above 50%, respectively.
      Column classification by principal component analysis of an extended retention
      map in comparison to a set of polar commercial and in-house synthesized
      stationary phases confirmed complementarity of the new mixed-mode phases with
      respect to HILIC, polar RP, amino and commercial mixed-mode phases. 

PMID- 26206630
TI  - Design and development of molecularly imprinted polymers for the selective
      extraction of deltamethrin in olive oil: An integrated computational-assisted
      approach.
AB  - This work firstly addresses the design and development of molecularly imprinted
      systems selective for deltamethrin aiming to provide a suitable sorbent for solid
      phase (SPE) extraction that will be further used for the implementation of an
      analytical methodology for the trace analysis of the target pesticide in spiked
      olive oil samples. To achieve this goal, a preliminary evaluation of the
      molecular recognition and selectivity of the molecularly imprinted polymers has
      been performed. In order to investigate the complexity of the mechanistic basis
      for template selective recognition in these polymeric matrices, the use of a
      quantum chemical approach has been attempted providing new insights about the
      mechanisms underlying template recognition, and in particular the crucial role of
      the crosslinker agent and the solvent used. Thus, DFT calculations corroborate
      the results obtained by experimental molecular recognition assays enabling one to
      select the most suitable imprinting system for MISPE extraction technique which
      encompasses acrylamide as functional monomer and ethylene glycol dimethacrylate
      as crosslinker. Furthermore, an analytical methodology comprising a sample
      preparation step based on solid phase extraction has been implemented using this
      "tailor made" imprinting system as sorbent, for the selective isolation/pre
      concentration of deltamethrin from olive oil samples. Molecularly imprinted solid
      phase extraction (MISPE) methodology was successfully applied for the clean-up of
      spiked olive oil samples, with recovery rates up to 94%. 

PMID- 26206631
TI  - Selective extraction and analysis of catecholamines in rat blood microdialysate
      by polymeric ionic liquid-diphenylboric acid-packed capillary column and fast
      separation in high-performance liquid chromatography-electrochemical detector.
AB  - Concentration of blood catecholamines (CAs) is linked to a host of cardiovascular
      diseases, including hypertension and stenocardia. The matrix interferences and
      low concentration require tedious sample pretreatment methods before quantitative
      analysis by the gold standard method of high-performance liquid chromatography
      electrochemical detector (HPLC-ECD). Solid phase extraction (SPE) has been widely
      used as the pretreatment technique. Here, a facile polymeric ionic liquid (PIL)
      diphenylboric acid (DPBA)-packed capillary column was prepared to selectively
      extract dopamine (DA), noradrenaline (NE) and epinephrine (E) prior to their
      quantitative analysis by a fast separation in HPLC-ECD method, while
      microdialysis sampling method was applied to get the analysis sample. Parameters
      that influenced desorption efficiency, such as pH, salt concentration,
      acetonitrile content and wash time, were examined and optimized. The proposed
      method, combining microdialysis sampling technique, SPE and HPLC-ECD system, was
      successfully applied to detect CAs in rat blood microdialysate with high
      sensitivity and selectivity in small sample volumes (5-40MUl) and a short
      analysis time (8min), yielding good reproducibility (RSD 6.5-7.7%) and spiked
      recovery (91-104.4%). 

PMID- 26206632
TI  - Winds of War: Enhancing Civilian and Military Partnerships to Assure Readiness:
      White Paper.
AB  - This White Paper summarizes the state of readiness of combat surgeons and
      provides action recommendations that address the problems of how to train,
      sustain, and retain them for future armed conflicts. As the basis for the 2014
      Scudder Oration, I explored how to secure an improved partnership between
      military and civilian surgery, which would optimize learning platforms and embed
      military trauma personnel at America's academic medical universities for trauma
      combat casualty care (TCCC). To craft and validate these recommendations, I
      conducted an integrative and iterative process of literature reviews, interviews
      of military and civilian leaders, and a survey of military-affiliated surgeons.
      The recommended action points advance the training of combat surgeons and their
      trauma teams by creating an expanded network of TCCC training sites and sourcing
      the cadre of combat-seasoned surgeons currently populating our civilian and
      military teaching hospitals and universities. The recommendation for the
      establishment of a TCCC readiness center or command within the Medical Health
      System of the Department of Defense includes a military and civilian advisory
      board, with the reformation of a think tank of content experts to address high
      level solutions for military medicine, readiness, and TCCC. 

PMID- 26206633
TI  - Invited Commentary.

PMID- 26206634
TI  - Per-Oral Endoscopic Myotomy: A Series of 500 Patients.
AB  - BACKGROUND: After the first case of per-oral endoscopic myotomy (POEM) at our
      institution in 2008, the procedure was quickly accepted as an alternative to
      surgical myotomy and is now established as an excellent treatment option for
      achalasia. This study aimed to examine the safety and outcomes of POEM at our
      institution. STUDY DESIGN: Per-oral endoscopic myotomy was performed on 500
      consecutive achalasia patients at our institution between September 2008 and
      November 2013. A review of prospectively collected data was conducted, including
      procedure time, myotomy location and length, adverse events, and patient data
      with short- (2 months) and long-term (1 and 3 years) follow-up. RESULTS: Per-oral
      endoscopic myotomy was successfully completed in all patients, with adverse
      events observed in 3.2%. Two months post-POEM, significant reductions in symptom
      scores (Eckardt score 6.0 +/- 3.0 vs 1.0 +/- 2.0, p < 0.0001) and lower
      esophageal sphincter (LES) pressures (25.4 +/- 17.1 vs 13.4 +/- 5.9 mmHg, p <
      0.0001) were achieved, and this persisted at 3 years post-POEM. Gastroesophageal
      reflux was seen in 16.8% of patients at 2 months and 21.3% at 3-year follow-up.
      CONCLUSIONS: Per-oral endoscopic myotomy was successfully completed in all cases,
      even when extended indications (extremes of age, previous interventions, or
      sigmoid esophagus) were used. Adverse events were rare (3.2%), and there were no
      mortalities. Significant improvements in Eckardt scores and LES pressures were
      seen at 2 months, 1 year, and 3 years post-POEM. Based on our large series, POEM
      is a safe and effective treatment for achalasia; there are relatively few
      contraindications, and the procedure may be used as either first- or second-line
      therapy.

PMID- 26206636
TI  - Intraoperative Use of a Portable Large Field of View Gamma Camera and Handheld
      Gamma Detection Probe for Radioguided Localization and Prediction of Complete
      Surgical Resection of Gastrinoma: Proof of Concept.
AB  - BACKGROUND: Surgical management of Zollinger-Ellison syndrome (ZES) relies on
      localization and resection of all tumor foci. We describe the benefit of combined
      intraoperative use of a portable large field of view gamma camera (LFOVGC) and a
      handheld gamma detection probe (HGDP) for indium-111 ((111)In)-pentetreotide
      radioguided localization and confirmation of gastrinoma resection in ZES. STUDY
      DESIGN: Five patients (6 cases) with (111)In-pentetreotide-avid ZES were
      evaluated. Patients were injected with (111)In-pentetreotide for diagnostic
      imaging the day before surgery. Intraoperatively, an HGDP and LFOVGC were used to
      localize (111)In-pentetreotide-avid lesions, guide resection, assess specimens
      for (111)In-pentetreotide activity, and to verify lack of abnormal post-resection
      surgical field activity. RESULTS: Large field of view gamma camera imaging and
      HGDP-assisted detection were helpful for localization and guided resection of
      tumor and removal of (111)In-pentetreotide-avid tumor foci in all cases. In 3 of
      5 patients (3 of 6 cases), these techniques led to detection and resection of
      additional tumor foci beyond those detected by standard surgical techniques. The
      (111)In-pentetreotide-positive or-negative specimens correlated with
      neuroendocrine tumors or benign pathology, respectively. In one patient with mild
      residual focal activity on post-resection portable LFOVGC imaging, thought to be
      artifact, had recurrence of disease in the same area 5 months after surgery.
      CONCLUSIONS: Real-time LFOVGC imaging and HGDP use for surgical management of
      gastrinoma improve success of localizing and resecting all neuroendocrine tumor
      positive tumor foci, providing instantaneous navigational feedback. This approach
      holds potential for improving long-term patient outcomes in patients with ZES.

PMID- 26206635
TI  - Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An
      Analysis from the US Gastric Cancer Collaborative.
AB  - BACKGROUND: Examination of at least 16 lymph nodes (LNs) has been traditionally
      recommended during gastric adenocarcinoma resection to optimize staging, but the
      impact of this strategy on survival is uncertain. Because recent randomized
      trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we
      sought to investigate the impact of the number of LNs removed on prognosis after
      gastric adenocarcinoma resection. STUDY DESIGN: We analyzed patients who
      underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US
      academic institutions. Patients with M1 disease or R2 resections were excluded.
      Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and
      compared using log-rank and Cox regression analyses. RESULTS: Of 742 patients,
      257 (35%) had 7 to 15 LNs removed and 485 (65%) had >=16 LNs removed. Disease
      specific survival was not significantly longer after removal of >=16 vs 7 to 15
      LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort,
      but was significantly improved in the subset of patients with stage IA to IIIA
      (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs
      55%, respectively; p = 0.023). Similarly, for patients who were classified to
      more likely be "true N0-2," based on frequentist analysis incorporating both the
      number of positive and of total LNs removed, the hazard ratio for disease-related
      death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant
      therapy, and institution) significantly decreased as the number of LNs removed
      increased. CONCLUSIONS: The number of LNs removed during gastrectomy for
      adenocarcinoma appears itself to have prognostic implications for long-term
      survival.

PMID- 26206637
TI  - Laparoscopic Splenectomy with Technical Standardization and Selection Criteria
      for Standard or Hand-Assisted Approach in 390 Patients with Liver Cirrhosis and
      Portal Hypertension.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) is still challenging in patients with
      liver cirrhosis and portal hypertension. This study was designed to establish
      safe and less invasive LS in patients with liver cirrhosis and portal
      hypertension. STUDY DESIGN: We analyzed 390 patients with liver cirrhosis and
      portal hypertension, who underwent LS between 1993 and 2013. Patients were
      divided into 3 time periods; early (1993 to 2004, n = 106); middle (2005 to 2008,
      n = 159); and late (2008 to 2013, n = 125). During the middle time period,
      standardized technique for LS and selection criteria for hand-assisted LS were
      adopted. Patients with spleen volume >= 1,000 mL by CT volumetry, large
      perisplenic collateral vessels, and/or Child-Pugh score >= 9, underwent hand
      assisted LS. During the late time period, the selection criteria were refined and
      patients with spleen volume >= 600 mL underwent hand-assisted LS. RESULTS:
      Conversion to open splenectomy decreased (10.4% in the early time period, 1.9% in
      the middle time period, and 3.2% in the late time period, p = 0.004), median
      blood loss decreased (300g, 87g, and 98g, respectively, p < 0.001), and the
      success rate of pure LS tended to improve (87.2%, 89.5%, and 98.0%, respectively,
      p = 0.110). Mortality was 0% in each time period, Clavien-Dindo grade IIIb or
      more complications tended to decrease (5.7%, 2.5%, and 0.8%, respectively, p =
      0.081), and technique-related complications decreased significantly (10.4%, 3.8%,
      and 2.4%, respectively, p = 0.014). CONCLUSIONS: Laparoscopic splenectomy is now
      a safe and less invasive approach, even in patients with liver cirrhosis and
      portal hypertension, because of its technical standardization with the refined
      selection criteria for pure or hand-assisted LS.

PMID- 26206638
TI  - Severe Jaundice Increases Early Severe Morbidity and Decreases Long-Term Survival
      after Pancreaticoduodenectomy for Pancreatic Adenocarcinoma.
AB  - BACKGROUND: The influence of jaundice on outcomes after pancreaticoduodenectomy
      (PD) for pancreatic ductal adenocarcinoma (PDAC) is debated. This study aimed to
      determine, in a large multicentric series, the influence of severe jaundice
      (serum bilirubin level >=250 MUmol/L and 300 MUmol/L) on early severe morbidity
      and survival after PD. STUDY DESIGN: From 2004 to 2009, twelve hundred patients
      (median age 66 years, 57% male) with resectable PDAC underwent PD. Patients who
      received preoperative biliary drainage for neoadjuvant treatment or cholangitis
      were excluded. Pre- and intraoperative data were collected by a standardized
      form. Serum bilirubin level and creatinine clearance were analyzed as categorical
      variables. Predictive factors of severe complications and poor survival (Kaplan
      Meier method) were identified by univariate and multivariate analysis. RESULTS:
      Median follow-up was 21 months (95% CI, 19-23). Operative mortality was 3.9% (n =
      47), with no predictive factors in multivariate analysis. Severe complications
      (Dindo-Clavien grade III to IV) occurred in 22% (n = 268), with male sex (p =
      0.025), America Society of Anesthesiologists score 3 to 4 (p = 0.022), serum
      bilirubin level >=300 MUmol/L (p = 0.034), and creatinine clearance <60
      mL/min/1.73 m(2) (p = 0.013) identified as predictive factors in multivariate
      analysis. Overall 3-year survival rate was 41% (95% CI, 37-45%). In multivariate
      analysis, serum bilirubin level >=300 MUmol/L (p = 0.048), low-volume center (p <
      0.001), venous resection (p = 0.014), N1 status (p < 0.01), R1 status (p <
      0.001), and absence of adjuvant treatment (p < 0.001) negatively impacted
      survival. There was a negative relationship between survival at 12 months or
      later and higher rates of bilirubin. Presence of a biliary stent did not
      influence early or long-term results. CONCLUSIONS: In this multicentric study,
      serum bilirubin level >=300 MUmol/L increased severe morbidity and decreased long
      term survival after PD for PDAC. These findings suggest that biliary stenting is
      appropriately indicated before PD in patients with PDAC and severe jaundice.

PMID- 26206639
TI  - Improving Outcomes in Colorectal Surgery by Sequential Implementation of Multiple
      Standardized Care Programs.
AB  - BACKGROUND: The purpose of this study was to examine the impact of the sequential
      implementation of the enhanced recovery program (ERP) and surgical site infection
      bundle (SSIB) on short-term outcomes in colorectal surgery (CRS) to determine if
      the presence of multiple standardized care programs provides additive benefit.
      STUDY DESIGN: Institutional ACS-NSQIP data were used to identify patients who
      underwent elective CRS from September 2006 to March 2013. The cohort was
      stratified into 3 groups relative to implementation of the ERP (February 1, 2010)
      and SSIB (July 1, 2011). Unadjusted characteristics and 30-day outcomes were
      assessed, and inverse proportional weighting was then used to determine the
      adjusted effect of these programs. RESULTS: There were 787 patients included:
      337, 165, and 285 in the pre-ERP/SSIB, post-ERP/pre-SSIB, and post-ERP/SSIB
      periods, respectively. After inverse probability weighting (IPW) adjustment,
      groups were balanced with respect to patient and procedural characteristics
      considered. Compared with the pre-ERP/SSIB group, the post-ERP/pre-SSIB group had
      significantly reduced length of hospitalization (8.3 vs 6.6 days, p = 0.01) but
      did not differ with respect to postoperative wound complications and sepsis.
      Subsequent introduction of the SSIB then resulted in a significant decrease in
      superficial SSI (16.1% vs 6.3%, p < 0.01) and postoperative sepsis (11.2% vs
      1.8%, p < 0.01). Finally, inflation-adjusted mean hospital cost for a CRS
      admission fell from $31,926 in 2008 to $22,044 in 2013 (p < 0.01). CONCLUSIONS:
      Sequential implementation of the ERP and SSIB provided incremental improvements
      in CRS outcomes while controlling hospital costs, supporting their combined use
      as an effective strategy toward improving the quality of patient care.

PMID- 26206640
TI  - Transanal Total Mesorectal Excision for Rectal Cancer: Outcomes after 140
      Patients.
AB  - BACKGROUND: The anatomic difficulties that we have to deal with in open surgery
      for rectal cancer have not been overcome with the laparoscopic approach. In the
      search for a solution, a change of concept arose: approaching the rectum from
      below. The main objectives of this study were to show the potential advantages of
      the hybrid transabdominal-transanal total mesorectal excision (taTME). This
      approach may improve quality of the mesorectal specimens. Second, proctectomy can
      be technically easier and more safely performed "down to up," which would result
      in shorter surgical times, lower conversion rates, and less morbidity. STUDY
      DESIGN: A prospective series of hybrid taTME was conducted from October 2011 to
      November 2014. RESULTS: During the study period, 140 procedures were performed.
      Mean operative time was 166 minutes. There were no conversions or intraoperative
      complications. Macroscopic quality assessment of the resected specimen was
      complete in 97.1% and nearly complete in 2.1%. Thirty-day morbidity was minor
      (Clavien-Dindo I + II) in 24.2% and major (Clavien-Dindo III + IV) in 10 %. No
      patient died within the first 30 days postsurgery (Clavien-Dindo V). The mean
      follow-up was 15 months, with a 2.3% local recurrence rate and a 7.6% rate of
      systemic recurrence. CONCLUSIONS: Pathologic analysis showed a very good
      macroscopic quality of TME specimens, which is the most important prognostic
      factor in rectal cancer. Intraoperative outcomes regarding conversion, surgical
      times, and intraoperative complications are very satisfactory. Short-term
      morbidity and oncologic outcomes are as good as in other laparoscopic TME series.

PMID- 26206641
TI  - Total Occlusive Ionic Silver-Containing Dressing vs Mupirocin Ointment
      Application vs Conventional Dressing in Elective Colorectal Surgery: Effect on
      Incisional Surgical Site Infection.
AB  - BACKGROUND: Several pre- and intraoperative factors have been associated with
      incisional surgical site infection (SSI), but little is known about the influence
      of postoperative wound care and especially, the use of different dressings on
      incisional SSI. The aim of this study was to compare 3 methods of wound dressings
      (conventional dressing, silver-containing dressing, and mupirocin ointment
      dressing) for their ability to prevent SSI, as measured by SSI rates, in patients
      with colorectal cancer undergoing elective open surgery. STUDY DESIGN: A
      prospective, randomized study was performed. Inclusion criteria were diagnosis of
      colorectal neoplasms and plans to undergo elective surgery with curative aims.
      Patients were randomized using a 1:1:1 allocation into 3 groups: patients
      receiving an ionic silver-containing dressing (ISD) (group 1), a mupirocin
      ointment application (MOA) (group 2), and a conventional dressing (group 3 or
      standard dressing). The primary outcomes variable was occurrence of incisional
      SSI. Follow-up was 30 days postoperatively. RESULTS: A total of 147 patients were
      included, 49 in each group. Incisional SSI occurred in 9 patients (18.4%) in the
      ISD group, 2 (4.1%) in the MOA group, and 10 (20.4%) in the standard dressing
      group (p = 0.028). Adjusting for multiple comparisons, there were no significant
      differences between ISD and standard dressing groups; a significant difference
      was observed between ISD and MOA (relative risk [RR] 4.5; 95% CI (1.1 to 19.8); p
      = 0.046) and between the standard group and the MOA group (RR 5; 95% CI (1.2 to
      21.7); p = 0.031). CONCLUSIONS: Topical application of mupirocin ointment
      achieves better results for the prevention of SSI than ionic silver-containing
      dressing or standard dressing in patients undergoing elective open colorectal
      surgery.

PMID- 26206642
TI  - Extended Intervals after Neoadjuvant Therapy in Locally Advanced Rectal Cancer:
      The Key to Improved Tumor Response and Potential Organ Preservation.
AB  - BACKGROUND: Many rectal cancer patients experience tumor downstaging and some are
      found to achieve a pathologic complete response (pCR) after neoadjuvant
      chemoradiotherapy (nCRT). Previous data suggest that there is an association
      between the time interval from nCRT completion to surgery and tumor response
      rates, including pCR. However, these studies have been primarily from single
      institutions with small sample sizes. The aim of this study was to examine the
      relationship between a longer interval after nCRT and pCR in a nationally
      representative cohort of rectal cancer patients. STUDY DESIGN: Clinical stage II
      to III rectal cancer patients undergoing nCRT with a documented surgical
      resection were selected from the 2006 to 2011 National Cancer Data Base.
      Multivariable logistic regression analysis was used to assess the association
      between the nCRT-surgery interval time (<6 weeks, 6 to 8 weeks, >8 weeks) and the
      odds of pCR. The relationship between nCRT-surgery interval, surgical morbidity,
      and tumor downstaging was also examined. RESULTS: Overall, 17,255 patients met
      the inclusion criteria. An nCRT-surgery interval time >8 weeks was associated
      with higher odds of pCR (odds ratio [OR] 1.12, 95% CI 1.01 to 1.25) and tumor
      downstaging (OR 1.11, 95% CI 1.02 to 1.25). The longer time delay was also
      associated with lower odds of 30-day readmission (OR 0.82, 95% CI 0.70 to 0.92).
      CONCLUSIONS: An nCRT-surgery interval time >8 weeks results in increased odds of
      pCR, with no evidence of associated increased surgical complications compared
      with an interval of 6 to 8 weeks. These data support implementation of a
      lengthened interval after nCRT to optimize the chances of pCR and perhaps add to
      the possibility of ultimate organ preservation (nonoperative management).

PMID- 26206644
TI  - Laparoscopic-Assisted Transversus Abdominis Plane Block for Postoperative Pain
      Control in Laparoscopic Ventral Hernia Repair: A Randomized Controlled Trial.
AB  - BACKGROUND: Laparoscopic ventral hernia repair (LVHR) is associated with
      considerable postoperative pain. Transversus abdominis plane (TAP) blocks have
      proven effective in controlling postoperative pain in a variety of laparoscopic
      abdominal operations. To date, no studies have focused on TAP blocks in LVHR. Our
      goal was to assess whether TAP blocks reduce opioid requirements and pain scores
      after LVHR. STUDY DESIGN: Patients undergoing LVHR were randomly assigned to
      receive a TAP block or placebo injection. The primary end points were cumulative
      opioid use at 1, 3, 6, 12, 18, and 24 hours postoperatively and pain scores
      recorded at 1 and 24 hours postoperatively. RESULTS: Patients in the experimental
      TAP group (n = 52) and control group (n = 48) were comparable with respect to
      patient demographics and clinical characteristics. In the postanesthesia care
      unit, the TAP group had significantly lower pain scores than the control group (p
      < 0.05). Patients in the TAP group used less opioids than the control group at
      each time point assessed after 6 hours postoperatively (p < 0.05). There was no
      significant difference in pain scores at 24 hours postoperatively (p > 0.05).
      CONCLUSIONS: Transversus abdominis plane blocks given during LVHR significantly
      decrease both short-term postoperative opioid use and pain experienced by
      patients.

PMID- 26206643
TI  - Outcomes after Resection of Intrahepatic Cholangiocarcinoma: External Validation
      and Comparison of Prognostic Models.
AB  - BACKGROUND: Published prognostic models for overall survival after liver
      resection for intrahepatic cholangiocarcinoma require external validation before
      use in clinical practice. STUDY DESIGN: From January 1993 to May 2013,
      consecutive patients who underwent resection of intrahepatic cholangiocarcinoma
      were identified from a prospective database. The Wang nomogram was derived in an
      Asian cohort (n = 367) and included clinicopathologic variables and preoperative
      CEA and cancer antigen 19-9 levels. The Hyder nomogram was derived in an Eastern
      and Western multicenter cohort (n = 514) using clinicopathologic variables only.
      The AJCC Cancer Staging System (7th ed) and the preoperative Fudan risk score
      were also evaluated. Prognostic performance was assessed in terms of
      discrimination, calibration, and stratification. RESULTS: One hundred and eighty
      eight patients were included, with a median follow-up of 41 months. Median
      overall survival was 48.7 months and estimated 3-year and 5-year overall survival
      rates were 59% and 45%, respectively. Overall survival prediction accuracy,
      according to concordance-index calculation, was 0.72 with the Wang nomogram, 0.66
      with the Hyder nomogram, 0.63 with the AJCC system, and 0.55 using the Fudan
      score. Both nomograms provided effective patient stratification in distinct
      survival groups. CONCLUSIONS: Both the Wang and Hyder nomograms provided accurate
      patient prognosis estimation after liver resection for intrahepatic
      cholangiocarcinoma and can be useful for decision making about adjuvant therapy.
      The Wang nomogram appears to be more appropriate in patients undergoing formal
      portal lymphadenectomy and requires preoperative CEA and cancer antigen 19-9
      levels for optimal performance.

PMID- 26206645
TI  - Previous Methicillin-Resistant Staphylococcus aureus Infection Independent of
      Body Site Increases Odds of Surgical Site Infection after Ventral Hernia Repair.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus infections can be
      difficult to manage in ventral hernia repair (VHR). We aimed to determine whether
      a history of preoperative MRSA infection, regardless of site, confers increased
      odds of 30-day surgical site infection (SSI) after VHR. STUDY DESIGN: A
      retrospective cohort study of patients undergoing VHR with class I to III wounds
      between 2005 and 2012 was performed using Vanderbilt University Medical Center's
      Perioperative Data Warehouse. Preoperative MRSA status, site of infection, and 30
      day SSI were determined. Univariate and multivariate analyses adjusting for
      confounding factors were performed to determine whether a history of MRSA
      infection was independently associated with SSIs. RESULTS: A total of 768 VHR
      patients met inclusion criteria, of which 46% were women. There were 54 (7%)
      preoperative MRSA infections (MRSA positive); 15 (28%) soft tissue, 9 (17%)
      bloodstream, 4 (7%) pulmonary, 3 (6%) urinary, and 5 (9%) other. Overall SSI rate
      was 10% (n = 80), SSI rate in the MRSA-positive group was 33% (n = 18), compared
      with 9% (n = 62) in controls (p < 0.001). Multivariate analysis demonstrated that
      a history of MRSA infection significantly increased odds of 30-day SSI after VHR
      by 2.3 times (95% CI, 1.1-4.8; p = 0.035). Other factors associated with
      postoperative SSI were performance of myofascial release, increasing BMI, length
      of operation, open repair, and clean-contaminated wound classification.
      CONCLUSIONS: A history of site-independent MRSA infection confers significantly
      increased odds of 30-day SSI after VHR. Additional investigation is needed to
      determine perioperative treatment regimens that might decrease odds of SSI in
      VHR, and optimal prosthetic types and techniques for this population.

PMID- 26206646
TI  - Adverse Events after Ventral Hernia Repair: The Vicious Cycle of Complications.
AB  - BACKGROUND: Ventral hernia repairs are one of the most common procedures
      performed by the general surgeon. They are also among the most complex procedures
      performed. We hypothesized that with each surgical failure, subsequent ventral
      hernia repair becomes more complicated and morbid. STUDY DESIGN: We assessed a
      multicenter database of patients who underwent an elective ventral hernia repair
      from 2000 to 2012 with at least 6 months of follow-up and elective repairs.
      Patients were evaluated by the number of previous ventral hernia repairs they
      had: primary ventral hernia repair (PVHR), first time incisional hernia repair
      (IHR1), second time incisional hernia repair (IHR2), or third time or greater
      incisional hernia repair (IHR3). The main outcomes measured were abdominal
      reoperation, operative duration, surgical site infection (SSI), and hernia
      recurrence. Complications were assessed and compared between the 4 groups. Time
      to recurrence was estimated using the Kaplan-Meier curve method by study cohort
      (PVHR, IHR1, IHR2, IHR3). RESULTS: A total of 794 patients were assessed; of
      these, 481 (60.6%) had PVHR, 207 (26.1%) had IHR1, 78 (9.8%) had IHR2, and 28
      (3.5%) had IHR3. Patients with multiple repairs were more likely to undergo
      subsequent reoperation, have a longer operative duration, develop SSI, and have a
      recurrence. At 140 months of follow-up, 37% of primary ventral hernias and 64% of
      incisional hernias have recurred. The highest recurrence rates are seen in IHR3,
      with 73% recurring. CONCLUSIONS: Previous ventral hernia repair increases the
      complication profile of repair, creating a vicious cycle of repair,
      complications, reoperation, and re-repair. Furthermore, long-term outcomes for
      ventral hernia repair are poor. Future studies should focus on hernia prevention
      and improving long-term outcomes after hernia repair.

PMID- 26206647
TI  - Impact of Hemorrhagic Shock on Pituitary Function.
AB  - BACKGROUND: Hypopituitarism after hypovolemic shock is well established in
      certain patient cohorts. However; the effects of hemorrhagic shock on pituitary
      function in trauma patients remains unknown. The aim of this study was to assess
      pituitary hormone variations in trauma patients with hemorrhagic shock. STUDY
      DESIGN: Patients with acute traumatic hemorrhagic shock presenting to our level 1
      trauma center were prospectively enrolled. Hemorrhagic shock was defined as
      systolic blood pressure (SBP) <= 90 mmHg on arrival or within 10 minutes of
      arrival in the emergency department, and requirement of >=2 units of packed red
      blood cell transfusion. Serum cortisol and serum pituitary hormones (vasopressin
      [ADH], adrenocorticotrophic hormone [ACTH], thyroid stimulating hormone [TSH],
      follicular stimulating hormone [FSH], and luteinizing hormone [LH]) were measured
      in each patient on admission and at 24, 48, 72, and 96 hours after admission.
      Outcome measure was variation in pituitary hormones. RESULTS: A total of 42
      patients were prospectively enrolled; mean age was 37 +/- 12 years, mean SBP 85.4
      +/- 64.5 mmHg, and median Injury Severity Score was 26 (range 18 to 38). There
      was an increase in the levels of cortisol (p < 0.001), a decrease in the levels
      of ACTH (p < 0.001) and ADH (p < 0.001), but no change in the levels of LH (p =
      0.30), FSH (p = 0.07), and TSH (p = 0.89) over 96 hours. Ten patients died during
      their hospital stay. Patients who died had higher mean admission ADH levels (p =
      0.03), higher mean admission ACTH levels (p < 0.001), and lower mean admission
      cortisol levels (p = 0.04) compared with patients who survived. CONCLUSIONS:
      Acute hypopituitarism does not occur in trauma patients with acute hemorrhagic
      shock. In patients who died, there was a decrease in cortisol levels, which
      appears to be adrenal in origin.

PMID- 26206648
TI  - Results of (68)Gallium-DOTATATE PET/CT Scanning in Patients with Multiple
      Endocrine Neoplasia Type 1.
AB  - BACKGROUND: Screening for neuroendocrine tumors (NETs) in patients with multiple
      endocrine neoplasia type 1 (MEN1) is recommended to detect primary and metastatic
      tumors, which can result in significant morbidity and mortality. The utility of
      somatostatin receptor imaging (68)Gallium-DOTATATE PET/CT in patients with MEN1
      is not known. The aim of this study was to prospectively determine the accuracy
      of (68)Gallium-DOTATATE PET/CT vs (111)In- pentetreotide single-photon emission
      CT (SPECT)/CT and anatomic imaging in patients with MEN1. STUDY DESIGN: We
      performed a prospective study comparing (68)Gallium-DOTATATE PET/CT, (111)In
      pentetreotide SPECT/CT, and triphasic CT scan to clinical, biochemical, and
      pathologic data in 26 patients with MEN1. RESULTS: (68)Gallium-DOTATATE PET/CT
      detected 107 lesions; (111)In-pentetreotide SPECT/CT detected 33 lesions; and CT
      scan detected 48 lesions. Lesions detected on (68)Gallium-DOTATATE PET/CT had
      high standard uptake value (SUV)(max) (median SUV(max) = 72.8 [range 19 to 191]).
      In 7 of the 26 patients (27%), (68)Gallium-DOTATATE PET/CT was positive, with a
      negative (111)In-pentetreotide SPECT/CT, and in 10 patients (38.5%), additional
      metastases were detected (range 0.3 cm to 1.5 cm). In 8 of the 26 patients (31%),
      there was a change in management recommendations as a result of the findings on
      (68)Gallium-DOTATATE PET/CT that were not seen on (111)In-pentetreotide SPECT/CT
      and CT scan. CONCLUSIONS: (68)Gallium-DOTATATE PET/CT is more sensitive for
      detecting NETs than (111)In-pentetreotide SPECT/CT and CT scan in patients with
      MEN1. This imaging technique should be integrated into radiologic screening and
      surveillance of patients with MEN1 because it can significantly alter management
      recommendations.

PMID- 26206649
TI  - Market Competition and Density in Liver Transplantation: Relationship to Volume
      and Outcomes.
AB  - BACKGROUND: Liver transplantation centers are unevenly distributed within the
      Donor Service Areas (DSAs) of the United States. This study assessed how market
      competition and liver transplantation center density are associated with liver
      transplantation volume within individual DSAs. STUDY DESIGN: We conducted a
      retrospective cohort study of 53,156 adult liver transplants in 45 DSAs with 110
      transplantation centers identified from the Scientific Registry of Transplant
      Recipients between 2003 and 2012. The following measures were derived annually
      for each DSA: market competition using the Herfindahl Hirschman Index,
      transplantation center density by the Average Nearest Neighbor method, liver
      quality by the Liver Donor Risk Index, and patient risk by the Model for End
      Stage Liver Disease. A hierarchical mixed effects negative binomial regression
      model of the relationship between liver transplants and market factors was
      created annually. Patient and graft survival were investigated with a Cox
      proportional hazards model. RESULTS: Transplantation center density was
      associated with market competition (p < 0.0001), listings for organ
      transplantation (p < 0.0001), and Model for End-Stage Liver Disease at
      transplantation (p = 0.0005). More liver transplantation centers (incidence rate
      ratio [IRR] = 1.03; p = 0.04), greater market competition (IRR = 1.36; p = 0.02),
      increased listings (IRR = 1.14; p < 0.0001), more donors (IRR = 1.24; p <
      0.0001), and higher Liver Donor Risk Index (IRR = 3.35; p < 0.0001) were
      associated with more transplants. No market variables were associated with
      increased mortality after transplantation. CONCLUSIONS: After controlling for
      demographic and market factors, a greater concentration of centers was associated
      with more liver transplants without impacting overall survival. These results
      warrant additional investigation into the relationship between geospatial factors
      and liver transplantation volume with consideration for the optimization of
      scarce resources.

PMID- 26206650
TI  - Influence of Cold Ischemia Time in Combination with Donor Acute Kidney Injury on
      Kidney Transplantation Outcomes.
AB  - BACKGROUND: Deceased-donor kidneys are often exposed to ischemic events from
      donor instability, as evidenced by acute kidney injury (AKI). Clinicians may be
      reluctant to transplant kidneys with AKI that also have prolonged cold ischemia
      time (CIT) for fear of an additional deleterious effect. STUDY DESIGN: We
      evaluated national data between 1998 and 2013 of adult first-time kidney-only
      recipients of paired kidneys from donors with AKI (terminal serum creatinine >= 2
      mg/dL), in which the CIT difference between recipients was >=1, 5, 10, or 15
      hours. RESULTS: On multivariate analysis of AKI kidney recipients, overall death
      censored graft survival (DCGS) was comparable between recipients with higher CIT
      relative to paired donor recipients with lower CIT when the CIT difference was at
      least 1 hour (adjusted hazard ratio [aHR] 0.98, 95% CI 0.85 to 1.13, n = 4,458),
      5 hours (aHR 0.97, 95% CI 0.79 to 1.18, n = 2,412), 10 hours (aHR 0.82, 95% CI
      0.59 to 1.15, n = 922), or 15 hours (aHR 0.94, 95% CI 0.57 to 1.58, n = 442).
      Overall patient survival of the longer CIT groups was comparable or protective
      with delta CIT of >=1 (aHR 0.94, 95% CI 0.83 to 1.06), 5 (aHR 0.80, 95% CI 0.68
      to 0.94), 10 (aHR 0.70, 95% CI 0.53 to 0.91), and 15 (aHR 0.64, 95%CI 0.43 to
      0.95) hours. Between each of the 4 delta-CIT levels of shorter and longer CIT,
      there were no statistically significant differences in the proportion of acute
      rejection at delta >=1, 5, 10, or 15 hours. CONCLUSIONS: These results suggest
      that in the setting of a previous ischemic donor event, prolonged CIT has limited
      bearing on long-term outcomes. This may be important evidence that despite the
      occurrence of other ischemic events, kidneys with prolonged CIT offer acceptable
      outcomes to recipients and are a potential source to expand the donor pool.

PMID- 26206651
TI  - Nonclinical Factors Associated with 30-Day Mortality after Lung Cancer Resection:
      An Analysis of 215,000 Patients Using the National Cancer Data Base.
AB  - BACKGROUND: Clinical variables associated with 30-day mortality after lung cancer
      surgery are well known. However, the effects of nonclinical factors, including
      insurance coverage, household income, education, type of treatment center, and
      area of residence, on short-term survival are less appreciated. We studied the
      National Cancer Data Base, a joint endeavor of the Commission on Cancer of the
      American College of Surgeons and the American Cancer Society, to identify
      disparities in 30-day mortality after lung cancer resection based on these
      nonclinical factors. STUDY DESIGN: We performed a retrospective cohort analysis
      of patients undergoing lung cancer resection from 2003 to 2011 using the National
      Cancer Data Base. Data were analyzed using a multivariable logistic regression
      model to identify risk factors for 30-day mortality. RESULTS: During our study
      period, 215,645 patients underwent lung cancer resection. We found that clinical
      variables, such as age, sex, comorbidity, cancer stage, preoperative radiation,
      extent of resection, positive surgical margins, and tumor size were associated
      with 30-day mortality after resection. Nonclinical factors, including living in
      lower-income neighborhoods with a lesser proportion of high school graduates, and
      receiving cancer care at a nonacademic medical center were also independently
      associated with increased 30-day postoperative mortality. CONCLUSIONS: This study
      represents the largest analysis of 30-day mortality for lung cancer resection to
      date from a generalizable national cohort. Our results demonstrate that, in
      addition to known clinical risk factors, several nonclinical factors are
      associated with increased 30-day mortality after lung cancer resection. These
      disparities require additional investigation to improve lung cancer patient
      outcomes.

PMID- 26206653
TI  - Assessment: Cornerstone in Wound Management.

PMID- 26206652
TI  - Goal-Directed Fluid Therapy Using Stroke Volume Variation for Resuscitation after
      Low Central Venous Pressure-Assisted Liver Resection: A Randomized Clinical
      Trial.
AB  - BACKGROUND: The optimal perioperative fluid resuscitation strategy for liver
      resections remains undefined. Goal-directed therapy (GDT) embodies a number of
      physiologic strategies to achieve an ideal fluid balance and avoid the
      consequences of over- or under-resuscitation. STUDY DESIGN: In a prospective
      randomized trial, patients undergoing liver resection were randomized to GDT
      using stroke volume variation as an end point or to standard perioperative
      resuscitation. Primary outcomes measure was 30-day morbidity. RESULTS: Between
      2012 and 2014, one hundred and thirty-five patients were randomized (GDT: n = 69;
      standard perioperative resuscitation: n = 66). Median age was 57 years and 56%
      were male. Metastatic disease comprised 81% of patients. Overall (35% GDT vs 36%
      standard perioperative resuscitation; p = 0.86) and grade 3 morbidity (28% GDT vs
      18% standard perioperative resuscitation; p = 0.22) were equivalent. Patients in
      the GDT arm received less intraoperative fluid (mean 2.0 L GDT vs 2.9 L standard
      perioperative resuscitation; p < 0.001). Perioperative transfusions were required
      in 4% (6% GDT vs 2% standard perioperative resuscitation; p = 0.37) and boluses
      in the postanesthesia care unit were administered to 24% (29% GDT vs 20% standard
      perioperative resuscitation; p = 0.23). Mortality rate was 1% (2 of 135 patients;
      both in GDT). On multivariable analysis, male sex, age, combined procedures,
      higher intraoperative fluid volume, and fluid boluses in the postanesthesia care
      unit were associated with higher 30-day morbidity. CONCLUSIONS: Stroke volume
      variation-guided GDT is safe in patients undergoing liver resection and led to
      less intraoperative fluid. Although the incidence of postoperative complications
      was similar in both arms, lower intraoperative resuscitation volume was
      independently associated with decreased postoperative morbidity in the entire
      cohort. Future studies should target extensive resections and identify patients
      receiving large resuscitation volumes, as this population is more likely to
      benefit from this technique.

PMID- 26206654
TI  - Can We Dispense with Ultrasonography in the Diagnosis of Acute Appendicitis?

PMID- 26206655
TI  - Evaluating Suspected Appendicitis: In reply to Muralidharan and colleagues.

PMID- 26206657
TI  - Central Pancreatectomy with Double Pancreaticojejunostomy.

PMID- 26206658
TI  - Three-Dimensional Virtual Endoscopy for Laparoscopic and Thoracoscopic Liver
      Resection.

PMID- 26206659
TI  - Reappraisal of a Dye-Staining Technique for Anatomic Hepatectomy by the
      Concomitant Use of Indocyanine Green Fluorescence Imaging.

PMID- 26206660
TI  - Indocyanine Green Fluorescence Angiography for Quantitative Evaluation of Gastric
      Tube Perfusion in Patients Undergoing Esophagectomy.

PMID- 26206661
TI  - Totally Laparoscopic Associating Liver Tourniquet and Portal Ligation for Staged
      Hepatectomy via Anterior Approach for Cirrhotic Hepatocellular Carcinoma.

PMID- 26206663
TI  - Breastfeeding and the risk of dental caries: a systematic review and meta
      analysis.
AB  - AIM: To synthesise the current evidence for the associations between
      breastfeeding and dental caries, with respect to specific windows of early
      childhood caries risk. METHODS: Systematic review, meta-analyses and narrative
      synthesis following searches of PubMed, CINAHL and EMBASE databases. RESULTS:
      Sixty-three papers included. Children exposed to longer versus shorter duration
      of breastfeeding up to age 12 months (more versus less breastfeeding), had a
      reduced risk of caries (OR 0.50; 95%CI 0.25, 0.99, I(2) 86.8%). Children
      breastfed >12 months had an increased risk of caries when compared with children
      breastfed <12 months (seven studies (OR 1.99; 1.35, 2.95, I(2) 69.3%). Amongst
      children breastfed >12 months, those fed nocturnally or more frequently had a
      further increased caries risk (five studies, OR 7.14; 3.14, 16.23, I(2) 77.1%).
      There was a lack of studies on children aged >12 months simultaneously assessing
      caries risk in breastfed, bottle-fed and children not bottle or breastfed,
      alongside specific breastfeeding practices, consuming sweet drinks and foods, and
      oral hygiene practices limiting our ability to tease out the risks attributable
      to each. CONCLUSION: Breastfeeding in infancy may protect against dental caries.
      Further research needed to understand the increased risk of caries in children
      breastfed after 12 months.

PMID- 26206662
TI  - Developmental influences on circuits programming susceptibility to obesity.
AB  - Suboptimal maternal nutrition exerts lasting impacts on obesity risk in
      offspring, but the direction of the effect is determined by the timing of
      exposure. While maternal undernutrition in early pregnancy is associated with
      increased body mass index, in later pregnancy it can be protective. The
      importance of the timing of maternal undernutrition is also observed in rodents,
      however, many of the processes that occur in the last trimester of human
      gestation are delayed to the postnatal period. Neonatal leptin administration
      exerts lasting impacts on susceptibility to obesity in rodents. Although leptin
      can influence the formation of hypothalamic circuits involved in homeostatic
      control of feeding during the postnatal period, these effects are too late to
      account for its ability to reverse adverse metabolic programming due to early
      gestational exposure to maternal undernutrition. This review presents an
      alternative framework for understanding the effects of neonatal leptin through
      influences on developing thermoregulatory circuits. 

PMID- 26206664
TI  - LTbetaR signalling preferentially accelerates oncogenic AKT-initiated liver
      tumours.
AB  - OBJECTIVES: The relative contributions of inflammatory signalling and sequential
      oncogenic dysregulation driving liver cancer pathogenesis remain incompletely
      understood. Lymphotoxin-beta receptor (LTbetaR) signalling is critically involved
      in hepatitis and liver tumorigenesis. Therefore, we explored the interdependence
      of inflammatory lymphotoxin signalling and specific oncogenic pathways in the
      progression of hepatic cancer. DESIGN: Pathologically distinct liver tumours were
      initiated by hydrodynamic transfection of oncogenic V-Akt Murine Thymoma Viral
      Oncogene Homolog 1 (AKT)/beta-catenin or AKT/Notch expressing plasmids. To
      investigate the relationship of LTbetaR signalling and specific oncogenic
      pathways, LTbetaR antagonist (LTbetaR-Fc) or agonist (anti-LTbetaR) were
      administered post oncogene transfection. Initiated livers/tumours were
      investigated for changes in oncogene expression, tumour proliferation,
      progression, latency and pathology. Moreover, specific LTbetaR-mediated molecular
      events were investigated in human liver cancer cell lines and through
      transcriptional analyses of samples from patients with intrahepatic
      cholangiocarcinoma (ICC). RESULTS: AKT/beta-catenin-transfected livers displayed
      increased expression of LTbeta and LTbetaR, with antagonism of LTbetaR signalling
      reducing tumour progression and enhancing survival. Conversely, enforced LTbetaR
      activation of AKT/beta-catenin-initiated tumours induced robust increases in
      proliferation and progression of hepatic tumour phenotypes in an AKT-dependent
      manner. LTbetaR-activation also rapidly accelerated ICC progression initiated by
      AKT/Notch, but not Notch alone. Moreover, LTbetaR-accelerated development
      coincides with increases of Notch, Hes1, c-MYC, pAKT and beta-catenin. We further
      demonstrate LTbetaR signalling in human liver cancer cell lines to be a regulator
      of Notch, pAKTser473 and beta-catenin. Transcriptome analysis of samples from
      patients with ICC links increased LTbetaR network expression with poor patient
      survival, increased Notch1 expression and Notch and AKT/PI3K signalling.
      CONCLUSIONS: Our findings link LTbetaR and oncogenic AKT signalling in the
      development of ICC.

PMID- 26206665
TI  - MDGA2 is a novel tumour suppressor cooperating with DMAP1 in gastric cancer and
      is associated with disease outcome.
AB  - BACKGROUND: Using the promoter methylation assay, we have shown that MDGA2 (MAM
      domain containing glycosylphosphatidylinositol anchor 2) is preferentially
      methylated in gastric cancer. We analysed its biological effects and prognostic
      significance in gastric cancer. METHODS: MDGA2 methylation status was evaluated
      by combined bisulfite restriction analysis and bisulfite genomic sequencing. The
      effects of MDGA2 re-expression or knockdown on cell proliferation, apoptosis and
      the cell cycle were determined. MDGA2 interacting protein was identified by mass
      spectrometry and MDGA2-related cancer pathways by reporter activity and PCR array
      analyses. The clinical impact of MDGA2 was assessed in 218 patients with gastric
      cancer. RESULTS: MDGA2 was commonly silenced in gastric cancer cells (10/11) and
      primary gastric cancers due to promoter hypermethylation. MDGA2 significantly
      inhibited cell proliferation by causing G1-S cell cycle arrest and inducing cell
      apoptosis in vitro, and suppressed xenograft tumour growth in both subcutaneous
      and orthotopic xenograft mouse models (both p<0.001). The anti-tumorigenic effect
      of MDGA2 was mediated through direct stabilising of DNA methyltransferase 1
      associated protein 1 (DMAP1), which played a tumour suppressive role in gastric
      cancer. This interaction activated their downstream key elements of p53/p21
      signalling cascades. Moreover, promoter methylation of MDGA2 was detected in
      62.4% (136/218) of gastric cancers. Multivariate analysis showed that patients
      with MDGA2 hypermethylation had a significantly decreased survival (p=0.005).
      Kaplan-Meier survival curves showed that MDGA2 hypermethylation was significantly
      associated with shortened survival in patients with early gastric cancer.
      CONCLUSIONS: MDGA2 is a critical tumour suppressor in gastric carcinogenesis; its
      hypermethylation is an independent prognostic factor in patients with gastric
      cancer.

PMID- 26206667
TI  - The Nature of Bonding between Argon and Mixed Gold-Silver Trimers.
AB  - The controversial nature of chemical bonding between noble gases and noble metals
      is addressed. Experimental evidence of exceptionally strong Au-Ar bonds in Ar
      complexes of mixed Au-Ag trimers is presented. IR spectra reveal an enormous
      influence of the attached Ar atoms on vibrational modes, particularly in Au-rich
      trimers, where Ar atoms are heavily involved owing to a relativistically enhanced
      covalency. In Ag-rich trimers, vibrational transitions of the metal framework
      predominate, indicating a pure electrostatic character of the Ag-Ar bonds. The
      experimental findings are analyzed by means of DFT calculations, which show how
      the relativistic differences between Au and Ag are manifested in stronger Au-Ar
      binding energies. Because of the ability to vary composition and charge
      distribution, the trimers serve as ideal model systems to study the chemical
      nature of the bonding of noble gases to closed-shell systems containing gold.

PMID- 26206666
TI  - Diagnostic yield and safety of sputum induction with nebulized racemic salbutamol
      versus hypertonic saline in smear-negative pulmonary tuberculosis.
AB  - OBJECTIVES: The aim of the study was to compare the diagnostic yield and safety
      profile of sputum induction (SI) with nebulized racemic salbutamol solution
      versus hypertonic saline in smear-negative pulmonary tuberculosis (TB). METHODS:
      The prospective study was conducted at Songklanagarind Hospital, Thailand.
      Suspected smear-negative pulmonary TB cases were recruited and randomized to
      receive SI with either nebulized racemic salbutamol solution or 3% sodium
      chloride (NaCl) solution. Induced sputum was examined with the acid-fast bacilli
      (AFB) smear test and cultured for Mycobacterium tuberculosis. The efficacy and
      adverse events of SI were analyzed. RESULTS: A total of 59 patients received SI
      with nebulized racemic salbutamol solution and 53 received 3% NaCl solution.
      There was no significant difference between the two groups in the average
      quantity of induced sputum (1.3 +/- 0.1 versus 1.2 +/- 0.2 ml, p = 0.5). The
      percentages of positive AFB smear and TB cultures in the salbutamol group were
      15% and 22%, and 13% and 17% in the 3% NaCl group (p = 0.5), respectively.
      Racemic salbutamol solution could increase the TB diagnostic yield similarly to
      3% NaCl, but incurred less chest tightness (5% versus 15%) and bronchospasm (0%
      versus 11.3%, p = 0.02) compared with 3% NaCl. CONCLUSIONS: SI by nebulized
      racemic salbutamol solution offers equal benefits to 3% NaCl solution in
      increasing both sputum quantity and diagnostic yield in smear-negative patients
      suspected of having pulmonary TB. Nebulized racemic salbutamol does not produce
      bronchospasm and chest tightness occurs less frequently than with 3% NaCl.
      Therefore, SI with nebulized racemic salbutamol solution should be considered as
      a good alternative noninvasive diagnostic tool for the diagnosis of pulmonary TB
      when hypertonic saline is unavailable or contraindicated.

PMID- 26206668
TI  - An in situ high-temperature scanning electron microscopy study of acanthite
      argentite phase transformation in nanocrystalline silver sulfide powder.
AB  - For the first time, the alpha-Ag2S (acanthite)-beta-Ag2S (argentite) phase
      transformation in nanocrystalline and coarse-crystalline powders of silver
      sulfide has been observed in situ by the scanning electron microscopy method in
      real-time. The argentite crystals are formed on the surface of acanthite
      particles as a result of electron-beam heating. According to the differential
      thermal analysis data, the transformation occurs at a temperature of ~449-450 K,
      and the enthalpy of transformation is equal to ~3.7-3.9 kJ mol(-1). The presence
      of alpha-Ag2S (acanthite)-beta-Ag2S (argentite) phase transformation is confirmed
      in situ by high-temperature X-ray diffraction data. 

PMID- 26206669
TI  - The La-related protein 1-specific domain repurposes HEAT-like repeats to directly
      bind a 5'TOP sequence.
AB  - La-related protein 1 (LARP1) regulates the stability of many mRNAs. These include
      5'TOPs, mTOR-kinase responsive mRNAs with pyrimidine-rich 5' UTRs, which encode
      ribosomal proteins and translation factors. We determined that the highly
      conserved LARP1-specific C-terminal DM15 region of human LARP1 directly binds a
      5'TOP sequence. The crystal structure of this DM15 region refined to 1.86 A
      resolution has three structurally related and evolutionarily conserved helix-turn
      helix modules within each monomer. These motifs resemble HEAT repeats, ubiquitous
      helical protein-binding structures, but their sequences are inconsistent with
      consensus sequences of known HEAT modules, suggesting this structure has been
      repurposed for RNA interactions. A putative mTORC1-recognition sequence sits
      within a flexible loop C-terminal to these repeats. We also present modelling of
      pyrimidine-rich single-stranded RNA onto the highly conserved surface of the DM15
      region. These studies lay the foundation necessary for proceeding toward a
      structural mechanism by which LARP1 links mTOR signalling to ribosome biogenesis.

PMID- 26206670
TI  - SETDB1, HP1 and SUV39 promote repositioning of 53BP1 to extend resection during
      homologous recombination in G2 cells.
AB  - Recent studies have shown that homologous recombination (HR) requires chromatin
      repression as well as relaxation at DNA double strand breaks (DSBs). HP1 and
      SUV39H1/2 are repressive factors essential for HR. Here, we identify SETDB1 as an
      additional compacting factor promoting HR. Depletion of HP1, SUV39, SETDB1 or
      BRCA1 confer identical phenotypes. The repressive factors, like BRCA1, are
      dispensable for the initiation of resection but promote the extension step
      causing diminished RPA or RAD51 foci and HR in irradiated G2 cells. Depletion of
      the compacting factors does not inhibit BRCA1 recruitment but at 8 h post IR,
      BRCA1 foci are smaller and aberrantly positioned compared to control cells. BRCA1
      promotes 53BP1 repositioning to the periphery of enlarged foci and formation of a
      devoid core with BRCA1 becoming enlarged and localized internally to 53BP1.
      Depletion of the compacting factors precludes these changes at irradiation
      induced foci. Thus, the repressive factors are required for BRCA1 function in
      promoting the repositioning of 53BP1 during HR. Additionally, depletion of these
      repressive factors in undamaged cells causes diminished sister chromatid
      association at centromeric sequences. We propose a model for how these findings
      may be functionally linked. 

PMID- 26206671
TI  - Accurate placement of substrate RNA by Gar1 in H/ACA RNA-guided
      pseudouridylation.
AB  - H/ACA RNA-guided ribonucleoprotein particle (RNP), the most complicated RNA
      pseudouridylase so far known, uses H/ACA guide RNA for substrate capture and four
      proteins (Cbf5, Nop10, L7Ae and Gar1) for pseudouridylation. Although it was
      shown that Gar1 not only facilitates the product release, but also enhances the
      catalytic activity, the chemical role that Gar1 plays in this complicated
      machinery is largely unknown. Kinetics measurement on Pyrococcus furiosus RNPs at
      different temperatures making use of fluorescence anisotropy showed that Gar1
      reduces the catalytic barrier through affecting the activation entropy instead of
      enthalpy. Site-directed mutagenesis combined with molecular dynamics simulations
      demonstrated that V149 in the thumb loop of Cbf5 is critical in placing the
      target uridine to the right position toward catalytic D85 of Cbf5. The enzyme
      elegantly aligns the position of uridine in the catalytic site with the help of
      Gar1. In addition, conversion of uridine to pseudouridine results in a rigid syn
      configuration of the target nucleotide in the active site and causes Gar1 to pull
      out the thumb. Both factors guarantee the efficient release of the product.

PMID- 26206674
TI  - Re: GreenLight(TM) Laser (XPS) Photoselective Vapo-Enucleation versus Holmium
      Laser Enucleation of the Prostate for the Treatment of Symptomatic Benign
      Prostatic Hyperplasia: a Randomized Controlled Study: A. M. Elshal, M. A.
      Elkoushy, A. R. El-Nahas, A. M. Shoma, A. Nabeeh, S. Carrier and M. M. ElhilaliJ
      Urol 2015; 193: 927-934.

PMID- 26206672
TI  - ChIP-seq reveals the global regulator AlgR mediating cyclic di-GMP synthesis in
      Pseudomonas aeruginosa.
AB  - AlgR is a key transcriptional regulator required for the expression of multiple
      virulence factors, including type IV pili and alginate in Pseudomonas aeruginosa.
      However, the regulon and molecular regulatory mechanism of AlgR have yet to be
      fully elucidated. Here, among 157 loci that were identified by a ChIP-seq assay,
      we characterized a gene, mucR, which encodes an enzyme that synthesizes the
      intracellular second messenger cyclic diguanylate (c-di-GMP). A DeltaalgR strain
      produced lesser biofilm than did the wild-type strain, which is consistent with a
      phenotype controlled by c-di-GMP. AlgR positively regulates mucR via direct
      binding to its promoter. A DeltaalgRDeltamucR double mutant produced lesser
      biofilm than did the single DeltaalgR mutant, demonstrating that c-di-GMP is a
      positive regulator of biofilm formation. AlgR controls the levels of c-di-GMP
      synthesis via direct regulation of mucR. In addition, the cognate sensor of AlgR,
      FimS/AlgZ, also plays an important role in P. aeruginosa virulence. Taken
      together, this study provides new insights into the AlgR regulon and reveals the
      involvement of c-di-GMP in the mechanism underlying AlgR regulation. 

PMID- 26206676
TI  - Reply.

PMID- 26206677
TI  - PLAID: a Syndrome of Complex Patterns of Disease and Unique Phenotypes.
AB  - PLCG2 associated antibody deficiency and immune dysregulation (PLAID) is a
      complex dominantly inherited disease characterized almost universally by cold
      urticaria, and variably by recurrent bacterial infection, autoimmunty and skin
      granuloma formation. Several striking phenotypes can emerge from this disease,
      and the pathophysiology leads to a complex mix of loss and gain of function in
      cellular signaling. This review discusses the key phenotypic characteristics and
      pathophysiologic observations seen in PLAID, and contrasts PLAID to several
      related disorders in order to best contextualize this fascinating disease. 

PMID- 26206675
TI  - Epigenetics and Systemic Lupus Erythematosus: Unmet Needs.
AB  - Systemic lupus erythematosus (SLE) is a chronic relapsing-remitting autoimmune
      disease affecting several organs. Although the management of lupus patients has
      improved in the last years, several aspects still remain challenging. More
      sensitive and specific biomarkers for an early diagnosis as well as for
      monitoring disease activity and tissue damage are needed. Genome-wide association
      and gene mapping studies have supported the genetic background for SLE
      susceptibility. However, the relatively modest risk association and the studies
      in twins have suggested a role for environmental and epigenetic factors, as well
      as genetic-epigenetic interaction. Accordingly, there is evidence that
      differences in DNA methylation, histone modifications, and miRNA profiling can be
      found in lupus patients versus normal subjects. Moreover, impaired DNA
      methylation on the inactive X-chromosome was suggested to explain, at least in
      part, the female prevalence of the disease. Epigenetic markers may be help in
      fulfilling the unmet needs for SLE by offering new diagnostic tools, new
      biomarkers for monitoring disease activity, or to better characterize patients
      with a silent clinical disease but with an active serology. Anti-DNA, anti
      phospholipid, and anti-Ro/SSA autoantibodies are thought to be pathogenic for
      glomerulonephritis, recurrent thrombosis and miscarriages, and neonatal lupus,
      respectively. However, tissue damage occurs occasionally or, in some patients,
      only in spite of the persistent presence of the antibodies. Preliminary studies
      suggest that epigenetic mechanisms may explain why the damage takes place in some
      patients only or at a given time. 

PMID- 26206678
TI  - A positive view on e-cigarettes.

PMID- 26206680
TI  - The Role of Synthetic Extracellular Matrices in Endothelial Progenitor Cell
      Homing for Treatment of Vascular Disease.
AB  - Poor vascular homeostasis drives many clinical disorders including diabetes,
      arthritis, atherosclerosis, and peripheral artery disease. Local tissue ischemia
      resultant of insufficient blood flow is a potent stimulus for recruitment of
      endothelial progenitor cells (EPCs). This mobilization and homing is a multi-step
      process involving EPC detachment from their steady state bone marrow niches,
      entry into circulation, rolling along vessel endothelium, transmigration, and
      adhesion to denuded extracellular matrix (ECM) where they may participate in
      neovessel formation. However, these events are often interrupted in pathological
      conditions partly due to an imbalance in factor presentation at the tissue level.
      EPC number and function is impaired in patients with vascular diseases and this
      dysfunction has been proposed as a prominent contributor to disease pathogenesis.
      Research approaches aimed at providing therapeutic angiogenesis commonly involve
      the delivery of proangiogenic cells and/or soluble factors. Nevertheless, greater
      understanding of the mechanisms involved in EPC homing in both healthy and
      diseased states is critical for improving efficacy of such strategies. This
      review underscores the matrix-related signals necessary for enhancing EPC
      recruitment to ischemic tissue and provides an overview of the development of
      synthetic ECMs that aim to mimic functions of the local native microenvironment
      for use in therapeutic angiogenesis. 

PMID- 26206681
TI  - Impact of shear rate pattern on upper and lower limb conduit artery endothelial
      function in both spinal cord-injured and able-bodied men.
AB  - NEW FINDINGS: What is the central question of this study? This study addresses
      the following two central questions. (i) What is the impact of vascular
      deconditioning after spinal cord injury (SCI) on shear rate patterns and
      endothelial function? (ii) What is the impact of acutely altered shear rate on
      endothelial function in both SCI and able-bodied control subjects? What is the
      main finding and its importance? Two main findings in the present study were as
      follows: (i) reduced superficial femoral artery endothelial function in the SCI
      group; and (ii) acutely altered shear rate decreased endothelial function in both
      SCI and able-bodied control subjects. These findings may shed some light on
      future interventions taking into account these regulatory mechanisms. Spinal cord
      injury (SCI) induces vascular deconditioning below the level of the lesion and
      disrupts sympathetic innervation of blood vessels. It is unclear how these
      changes affect shear rate (SR) profiles and endothelial function when compared
      with able-bodied (AB) persons. Recent evidence suggests that periods of increased
      retrograde SR are associated with acute decreases in endothelial function, but is
      unknown how modified SR patterns influence sublesional vasculature in SCI. The
      present study examined the acute and chronic effects of altered SR patterns and
      oscillatory shear index on endothelial function via relative flow-mediated
      dilatation (FMD%) in both the brachial and superficial femoral arteries (BA and
      SFA, respectively) of eight individuals with SCI and eight matched AB control
      subjects. Baseline BA SR patterns and FMD% were similar between groups, while SFA
      anterograde SR was higher (P < 0.01) and FMD% lower (P = 0.04) in SCI versus AB
      subjects. Shear rate patterns were then acutely altered through the BA and SFA
      using a subsystolic cuff-inflation model. Bilateral FMD assessments were
      conducted before and after 30 min of unilateral inflation of a forearm or thigh
      blood pressure cuff to 75 mmHg. Cuff inflation resulted in concomitant increases
      in both anterograde (P < 0.05) and retrograde SR (P < 0.05), as well as acute
      decreases in FMD% (P < 0.05) in the BA and SFA in both groups. These results
      highlight that brief manipulation of SR patterns can acutely impair FMD% in
      conditions of both normal and altered sympathetic innervation and arterial
      remodelling. This information is crucial when designing strategies to combat
      impaired vascular function in both healthy and clinical populations.

PMID- 26206679
TI  - Predicting Knee Osteoarthritis.
AB  - Treatment options for osteoarthritis (OA) beyond pain relief or total knee
      replacement are very limited. Because of this, attention has shifted to
      identifying which factors increase the risk of OA in vulnerable populations in
      order to be able to give recommendations to delay disease onset or to slow
      disease progression. The gold standard is then to use principles of risk
      management, first to provide subject-specific estimates of risk and then to find
      ways of reducing that risk. Population studies of OA risk based on statistical
      associations do not provide such individually tailored information. Here we argue
      that mechanistic models of cartilage tissue maintenance and damage coupled to
      statistical models incorporating model uncertainty, united within the framework
      of structural reliability analysis, provide an avenue for bridging the
      disciplines of epidemiology, cell biology, genetics and biomechanics. Such models
      promise subject-specific OA risk assessment and personalized strategies for
      mitigating or even avoiding OA. We illustrate the proposed approach with a simple
      model of cartilage extracellular matrix synthesis and loss regulated by daily
      physical activity. 

PMID- 26206682
TI  - Clinicopathology of diffuse intrinsic pontine glioma and its redefined genomic
      and epigenomic landscape.
AB  - Diffuse intrinsic pontine glioma (DIPG) is one of the most lethal pediatric
      central nervous system (CNS) cancers. Recently, a surge in molecular studies of
      DIPG has occurred, in large part due to the increased availability of tumor
      tissue through donation of post-mortem specimens. These new discoveries have
      established DIPGs as biologically distinct from adult gliomas, harboring unique
      genomic aberrations. Mutations in histone encoding genes are shown to be
      associated with >70% of DIPG cases. However, the exact molecular mechanisms of
      the tumorigenicity of these mutations remain elusive. Understanding the driving
      mutations and genomic landscape of DIPGs can now guide the development of
      targeted therapies for this incurable childhood cancer. 

PMID- 26206683
TI  - Multicenter study of antimicrobial susceptibility of anaerobic bacteria in Korea
      in 2012.
AB  - BACKGROUND: Periodic monitoring of regional or institutional resistance trends of
      clinically important anaerobic bacteria is recommended, because the resistance of
      anaerobic pathogens to antimicrobial drugs and inappropriate therapy are
      associated with poor clinical outcomes. There has been no multicenter study of
      clinical anaerobic isolates in Korea. We aimed to determine the antimicrobial
      resistance patterns of clinically important anaerobes at multiple centers in
      Korea. METHODS: A total of 268 non-duplicated clinical isolates of anaerobic
      bacteria were collected from four large medical centers in Korea in 2012.
      Antimicrobial susceptibility was tested by the agar dilution method according to
      the CLSI guidelines. The following antimicrobials were tested: piperacillin,
      piperacillin-tazobactam, cefoxitin, cefotetan, imipenem, meropenem, clindamycin,
      moxifloxacin, chloramphenicol, metronidazole, and tigecycline. RESULTS: Organisms
      of the Bacteroides fragilis group were highly susceptible to piperacillin
      tazobactam, imipenem, and meropenem, as their resistance rates to these three
      antimicrobials were lower than 6%. For B. fragilis group isolates and anaerobic
      gram-positive cocci, the resistance rates to moxifloxacin were 12-25% and 11-13%,
      respectively. Among B. fragilis group organisms, the resistance rates to
      tigecycline were 16-17%. Two isolates of Finegoldia magna were non-susceptible to
      chloramphenicol (minimum inhibitory concentrations of 16-32 mg/L). Resistance
      patterns were different among the different hospitals. CONCLUSIONS: Piperacillin
      tazobactam, cefoxitin, and carbapemems are highly active beta-lactam agents
      against most of the anaerobes. The resistance rates to moxifloxacin and
      tigecycline are slightly higher than those in the previous study.

PMID- 26206684
TI  - Detection of first-line anti-tuberculosis drug resistance mutations by allele
      specific primer extension on a microsphere-based platform.
AB  - BACKGROUND: Resistance of Mycobacterium tuberculosis to anti-tuberculosis (TB)
      drugs is almost exclusively due to spontaneous chromosomal mutations in target
      genes. Rapid detection of drug resistance to both first- and second-line anti-TB
      drugs has become a key component of TB control programs. Technologies that allow
      rapid, cost-effective, and high-throughput detection of specific nucleic acid
      sequences are needed. This study was to develop a high-throughput assay based on
      allele-specific primer extension (ASPE) and MagPlex-TAG microspheres to detect
      anti-TB drug resistance mutations. METHODS: DNA samples from 357 M. tuberculosis
      clinical isolates and H37Rv were amplified by multiplex PCR using four primer
      sets, followed by multiplex ASPE using 23 TAG-ASPE primers. The products were
      sorted on the TAG-ASPE array and detected by using the Luminex xMAP system.
      Genotypes were also determined by sequencing. RESULTS: Genetic drug
      susceptibility typing by the TAG-ASPE method was 100% concordant with those
      obtained by sequencing. Compared with phenotypic drug susceptibility testing
      (DST) as a reference method, the sensitivity and specificity of the TAG-ASPE
      method were 83% (95% confidence interval [CI], 79-88%) and 97% (95% CI, 90-100%)
      for isoniazid. For rifampin testing, the sensitivity and specificity were 90%
      (95% CI, 86-93%) and 100% (95% CI, 99-100%). Also, the sensitivity and
      specificity were 58% (95% CI, 51-65%) and 86% (95% CI, 79-93%) for ethambutol.
      CONCLUSIONS: This study demonstrated the TAG-ASPE method is suitable for highly
      reproducible, cost-effective, and high-throughput clinical genotyping
      applications.

PMID- 26206685
TI  - Phenotypic and genotypic analysis of anti-tuberculosis drug resistance in
      Mycobacterium tuberculosis isolates in Myanmar.
AB  - BACKGROUND: Tuberculosis (TB) is one of the most serious health problems in
      Myanmar. Because TB drug resistance is associated with genetic mutation(s)
      relevant to responses to each drug, genotypic methods for detecting these
      mutations have been proposed to overcome the limitations of classic phenotypic
      drug susceptibility testing (DST). We explored the current estimates of drug
      resistant TB and evaluated the usefulness of genotypic DST in Myanmar. METHODS:
      We determined the drug susceptibility of Mycobacterium tuberculosis isolated from
      sputum smear-positive patients with newly diagnosed pulmonary TB at two main TB
      centers in Myanmar during 2013 by using conventional phenotypic DST and the
      GenoType MTBDRplus assay (Hain Lifescience, Germany). Discrepant results were
      confirmed by sequencing the genes relevant to each type of resistance (rpoB for
      rifampicin; katG and inhA for isoniazid). RESULTS: Of 191 isolates, phenotypic
      DST showed that 27.7% (n=53) were resistant to at least one first-line drug and
      20.9% (n=40) were resistant to two or more, including 18.3% (n=35) multidrug
      resistant TB (MDR-TB) strains. Monoresistant strains accounted for 6.8% (n=13) of
      the samples. Genotypic assay of 189 isolates showed 17.5% (n=33) MDR-TB and 5.3%
      (n=10) isoniazid-monoresistant strains. Genotypic susceptibility results were
      99.5% (n=188) concordant and agreed almost perfectly with phenotypic DST
      (kappa=0.99; 95% confidence interval 0.96-1.01). CONCLUSIONS: The results
      highlight the burden of TB drug resistance and prove the usefulness of the
      genotypic DST in Myanmar.

PMID- 26206686
TI  - Evaluation of dual-color fluorescence in situ hybridization with peptide nucleic
      acid probes for the detection of Mycobacterium tuberculosis and non-tuberculous
      mycobacteria in clinical specimens.
AB  - BACKGROUND: Peptide nucleic acid (PNA) probes are artificial DNA analogues with a
      hydrophobic nature that can penetrate the mycobacterial cell wall. We evaluated a
      FISH method for simultaneous detection and identification of Mycobacterium
      tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) in clinical respiratory
      specimens using differentially labeled PNA probes. METHODS: PNA probes targeting
      the mycobacterial 16S ribosomal RNA were synthesized. The cross-reactivity of MTB
      and NTM-specific probes was examined with reference strains and 10 other
      frequently isolated bacterial species. A total of 140 sputum specimens were
      analyzed, comprising 100 MTB-positive specimens, 21 NTM-positive specimens, and
      19 MTB/NTM-negative specimens; all of them were previously confirmed by PCR and
      culture. The PNA FISH test results were graded by using the United States Centers
      for Disease Control and Prevention-recommended scale and compared with the
      results from the fluorochrome acid-fast bacterial stain. RESULTS: The MTB- and
      NTM-specific PNA probes showed no cross-reactivity with other tested bacterial
      species. The test results demonstrated 82.9% agreement with the culture results
      with diagnostic sensitivity of 80.2% and diagnostic specificity of 100.0%
      (kappa=0.52, 95% confidence interval: 0.370-0.676). CONCLUSIONS: Dual-color PNA
      FISH showed high specificity for detecting and identifying mycobacteria in
      clinical specimens. However, because of its relatively low sensitivity, this
      method could be more applicable to culture confirmation. In application to direct
      specimens, the possibility of false-negative results needs to be considered.

PMID- 26206687
TI  - Therapeutic plasma exchange using the Spectra Optia cell separator compared with
      the COBE Spectra.
AB  - BACKGROUND: The Spectra Optia (SPO) is a novel continuous-flow centrifugal
      apheresis system based on the COBE Spectra (CSP) platform. There have been few
      attempts to validate the advantages of the SPO. We performed a retrospective
      study comparing the two cell separators for therapeutic plasma exchange (TPE)
      procedures in kidney transplant (KT) patients and seeing efficacy and safety.
      METHODS: We analyzed 720 TPE procedures performed between August 2012 and July
      2014. Procedures included desensitization TPE before KT and TPE for the
      management of acute and chronic antibody-mediated graft rejection. Demographic
      characteristics, operational TPE variables, and laboratory data were analyzed.
      RESULTS: Demographic characteristics for the SPO (n=389) and CSP (n=331) groups
      did not differ significantly. The procedure time to exchange one plasma volume
      was 94.2+/-10.3 min in the SPO group and 100.4+/-11.2 min in the CSP group
      (P<0.001). The plasma removal efficiency (PRE) was 92.5+/-4.9% in the SPO group
      and 83.2+/-3.7% in the CSP group (P<0.001). There were no significant differences
      across the two apheresis systems for changes in hematologic parameters.
      CONCLUSIONS: Compared with the CSP, the SPO was associated with an improved PRE
      and a shorter procedure time to exchange one plasma volume. Our results in KT
      patients show that the SPO is superior to the CSP in TPE procedures.

PMID- 26206688
TI  - Routine chromosomal microarray analysis is necessary in Korean patients with
      unexplained developmental delay/mental retardation/autism spectrum disorder.
AB  - BACKGROUND: All over the world, chromosomal microarray (CMA) is now the first
      tier diagnostic assay for genetic testing to evaluate developmental delay (DD),
      mental retardation (MR), and autism spectrum disorder (ASD) with unknown
      etiology. The average diagnostic yield of the CMA test is known to be about
      12.2%, while that of conventional G-banding karyotype is below 3%. This study
      aimed to assess the usefulness of CMA for the purpose of clinical diagnostic
      testing in the Korean population. METHODS: We performed CMA and multiplex
      ligation-dependent probe amplification (MLPA) tests in 96 patients with normal
      karyotype and unexplained DD, MR, or ASD. The CMA was conducted with CytoScan
      750K array (Affymetrix, USA) with an average resolution of 100 kb. RESULTS:
      Pathogenic copy number variations (CNVs) were detected in 15 patients by CMA and
      in two patients by MLPA for four known microdeletion syndromes (Prader
      Willi/Angelman syndrome, DiGeorge syndrome, Miller-Dieker syndrome and Williams
      syndrome) designated by National Health Insurance system in Korea. The diagnostic
      yield was 15.6% and 2.1%, respectively. Thirteen (13.5%) patients (excluding
      cases with pathogenic CNVs) had variants of uncertain clinical significance.
      There was one patient with a 17.1-megabase (Mb) region of homozygosity on
      chromosome 4q. CONCLUSIONS: Our findings suggest the necessity of CMA as a
      routine diagnostic test for unexplained DD, MR, and ASD in Korea.

PMID- 26206689
TI  - Development and validation of liquid chromatography-tandem mass spectrometry
      method for quantification of plasma metanephrines for differential diagnosis of
      adrenal incidentaloma.
AB  - High-resolution imaging techniques have increased the detection rate of adrenal
      incidentaloma. We developed a method of liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) for detection of plasma free metanephrine (MN) and
      normetanephrine (NMN) and evaluated its analytical performance and clinical
      efficacy in differential diagnosis of adrenal incidentaloma. After solid-phase
      extraction, chromatographic isolation of the analytes and internal standard was
      achieved by column elution in the LC-MS/MS system. The analytes were detected in
      multiple-reaction monitoring mode by using positive electrospray ionization: MN,
      transition m/z 180.1-->165.1; NMN, m/z 166.1-->134.1. This method was validated
      for linearity, precision, accuracy, lower limits of quantification and detection,
      extraction recovery, and the matrix effect. Plasma concentrations of MN and NMN
      of 14 patients with pheochromocytoma were compared with those of 17 healthy
      volunteers, 10 patients with essential hypertension, and 60 patients with adrenal
      adenoma. The assay's linear range was 0.04-50.0 and 0.08-100.0 nmol/L for MN and
      NMN, respectively. Assay imprecision was 1.86-7.50%. The accuracy ranged from 
      7.50% to 2.00%, and the mean recovery of MN and NMN was within the range 71.5
      95.2%. Our LC-MS/MS method is rapid, accurate, and reliable and useful for
      differential diagnosis of adrenal incidentaloma. 

PMID- 26206690
TI  - In vitro activity of tedizolid against gram-positive bacteria in patients with
      skin and skin structure infections and hospital-acquired pneumonia: a Korean
      multicenter study.
AB  - We compared the activities of tedizolid to those of linezolid and other commonly
      used antimicrobial agents against gram-positive cocci recovered from patients
      with skin and skin structure infections (SSSIs) and hospital-acquired pneumonia
      (HAP) in Korean hospitals. Gram-positive isolates were collected from 356
      patients with SSSIs and 144 patients with HAP at eight hospitals in Korea from
      2011 to 2014. SSSIs included impetigo, cellulitis, erysipelas, furuncles,
      abscesses, and infected burns. Antimicrobial susceptibility was tested by using
      the CLSI agar dilution method. All of the gram-positive isolates were inhibited
      by <=1 MUg/mL tedizolid. The minimum inhibitory concentration [MIC]90 of
      tedizolid was 0.5 MUg/mL for methicillin-resistant Staphylococcus aureus, which
      was 4-fold lower than that of linezolid. Tedizolid may become a useful option for
      the treatment of SSSIs and HAP caused by gram-positive bacteria. 

PMID- 26206691
TI  - Emergence of Acinetobacter pittii harboring New Delhi metallo-beta-lactamase
      genes in Daejeon, Korea.
AB  - Carbapenemase production has been reported worldwide in gram-negative bacteria,
      including Acinetobacter species. We detected carbapenemase-producing
      Acinetobacter pittii in clinical isolates in Daejeon, Korea. Twenty-one ertapenem
      resistant A. pittii isolates screened with a disk diffusion method were
      characterized by using the Epsilon test, four multiplex PCR assays, and a
      multilocus sequence typing (MLST) scheme. A total of 21 A. pittii isolates
      harbored the metallo-beta-lactamase (MBL) gene bla(IMP-1) or bla(NDM-1). Nineteen
      isolates containing bla(IMP-1) were resistant to imipenem and meropenem, but two
      isolates harboring bla(NDM-1) were susceptible to them. The sequence types (STs)
      of the two New Delhi MBL (NDM-1)-producing A. pittii isolates were ST70 and
      ST207, which differed from the STs (ST63, ST119, ST396, and a novel ST) of the
      IMP-1-producing A. pittii. This is the first report on NDM-1-producing A. pittii
      isolates in Korea. Our results emphasize that the study of NDM-1-producing gram
      negative bacteria should involve carbapenem-susceptible as well as carbapenem
      resistant isolates. 

PMID- 26206693
TI  - The e1a3 BCR-ABL1 fusion transcript in philadelphia chromosome-positive acute
      lymphoblastic leukemia.

PMID- 26206692
TI  - CYP21A2 mutation analysis in Korean patients with congenital adrenal hyperplasia
      using complementary methods: sequencing after long-range PCR and restriction
      fragment length polymorphism analysis with multiple ligation-dependent probe
      amplification assay.
AB  - CYP21A2 mutation analysis of congenital adrenal hyperplasia (CAH) is challenging
      because of the genomic presence of a homologous CYP21A2 pseudogene and the
      significant incidence of pseudogene conversion and large deletions. The objective
      of this study was to accurately analyze the CYP21A2 genotype in Korean CAH
      patients using a combination of complementary methods. Long-range PCR and
      restriction fragment length polymorphism analyses were performed to confirm valid
      amplification of CYP21A2 and to detect large gene conversions and deletions
      before direct sequencing. Multiple ligation-dependent probe amplification (MLPA)
      analysis was conducted concurrently in 14 CAH-suspected patients and six family
      members of three patients. We identified 27 CYP21A2 mutant alleles in 14 CAH
      suspected patients. The c.293-13A>G (or c.293-13C>G) was the most common
      mutation, and p.Ile173Asn was the second, identified in 25% and 17.9% of alleles,
      respectively. A novel frame-shift mutation of c.492delA (p.Glu 164Aspfs*24) was
      detected. Large deletions were detected by MLPA in 10.7% of the alleles. Mutation
      studies of the six familial members for three of the patients aided in the
      identification of haplotypes. In summary, we successfully identified CYP21A2
      mutations using both long-range PCR and sequencing and dosage analyses. Our data
      correspond relatively well with the previously reported mutation spectrum
      analysis. 

PMID- 26206694
TI  - Re: Lee H, et al. An unusual case of myeloperoxidase-positive acute
      megakaryoblastic leukemia. Ann Lab Med 2015;35:466-8.

PMID- 26206695
TI  - Immature teratoma and subsequent acute promyelocytic leukemia in a pediatric
      patient with XYY syndrome.

PMID- 26206696
TI  - Central venous catheter-related bloodstream infection by Corynebacterium striatum
      identified by 16S rRNA and rpoB gene sequencing.

PMID- 26206697
TI  - Loss of mismatched HLA detected in the peripheral blood of an AML patient who
      relapsed after haploidentical hematopoietic stem cell transplantation.

PMID- 26206698
TI  - Primary anti-D alloimmunization induced by "Asian type" RHD (c.1227G>A) DEL red
      cell transfusion.

PMID- 26206700
TI  - Erratum: flow cytometric white blood cell differential using cytodiff is
      excellent for counting blasts.

PMID- 26206699
TI  - Phenotypic variability of a terminal 7q deletion/8q duplication in Korean
      siblings.

PMID- 26206701
TI  - Critical review of studies trying to evaluate the treatment of chronic Lyme
      disease.

PMID- 26206702
TI  - [Lyme disease: where is the controversy?].

PMID- 26206703
TI  - Erratum: FoxO1 integrates direct and indirect effects of insulin on hepatic
      glucose production and glucose utilization.

PMID- 26206704
TI  - Detecting a wide range of environmental contaminants in human blood samples-
      combining QuEChERS with LC-MS and GC-MS methods.
AB  - Exposure to environmental pollution and consumer products may result in an uptake
      of chemicals into human tissues. Several studies have reported the presence of
      diverse environmental contaminants in human blood samples. However, previously
      developed multi-target methods for the analysis of human blood include a fairly
      limited amount of compounds stemming from one or two related compound groups.
      Thus, the sample preparation method QuEChERS (quick easy cheap effective rugged
      and safe) was tested for the extraction of 64 analytes covering a broad compound
      domain followed by detection using liquid and gas chromatography coupled to mass
      spectrometry (LC- and GC-MS). Forty-seven analytes showed absolute recoveries
      above 70% in the first QuEChERS step, being a simple liquid-liquid extraction
      (LLE) using acetonitrile and salt. The second QuEChERS step, being a dispersive
      solid phase extraction, did not result in an overall improvement of recoveries or
      removal of background signals. Using solely the LLE step, eight analytes could
      subsequently be detected in human blood samples from the German Environmental
      Specimen Bank. Using a LC-multiple reaction monitoring (MRM) method with a triple
      quadrupole instrument, better recoveries were achieved than with an older LC-high
      resolution (HR) MS full scan orbitrap instrument, which required a higher
      concentration factor of the extracts. However, the application of HRMS full scan
      methods could be used for the detection of additional compounds retrospectively.

PMID- 26206705
TI  - Accurate purification age determination of individual uranium-plutonium mixed
      particles.
AB  - Age of individual uranium-plutonium (U/Pu) mixed particles with various U/Pu
      atomic ratios (1-70) were determined by inductively coupled plasma mass
      spectrometry. Micron-sized particles were prepared from U and Pu certified
      reference materials. The Pu reference was stored for 4-6 years since the last
      purification (July 14, 2008). The Pu purification age was obtained from the
      (241)Am/(241)Pu ratio which was calculated from the product of three measured
      ratios of Pu and Am isotopes in the eluted fractions. These ratios were measured
      by a high-resolution inductively coupled plasma mass spectrometer equipped with a
      desolvation system. Femto-gram to pico-gram quantities of Am, U, and Pu in a
      sample solution were sequentially separated on a small anion-exchange column. The
      (241)Am/(241)Pu ratio was accurately determined by spiking pure (243)Am into the
      sample solution. The average determined age for the particles for the five
      independent U/Pu ratios was in good agreement with the expected age with high
      accuracy (difference age 0.27 years) and high precision (standard deviation 0.44
      years). The described analytical technique can serve as an effective tool for
      nuclear safeguards and environmental radiochemistry. Figure Young (4-6 y) Pu
      purification age of individual U/Pu mixed micron-sized reference particles for
      the five independent U/Pu ratios (1-70) were determined with 0.27+/-0.44 y
      difference from the expected age. Sub pico-gram quantities of Am, U and Pu were
      sequentially separated a small column, and their isotope ratios were accurately
      measured using an ICP-MS by applying the (243)Am spiking technique to the
      analysis and correcting the impurity and the contaminations.

PMID- 26206706
TI  - Highly sensitive simultaneous quantification of estrogenic tamoxifen metabolites
      and steroid hormones by LC-MS/MS.
AB  - Tamoxifen is a mainstay in the treatment of estrogen receptor-positive breast
      cancer and is metabolized to more than 30 different compounds. Little is known
      about in vivo concentrations of estrogenic metabolites E-metabolite E, Z
      metabolite E, and bisphenol and their relevance for tamoxifen efficacy.
      Therefore, we developed a highly sensitive HPLC-ESI-MS/MS quantification method
      for tamoxifen metabolites bisphenol, E-metabolite E, and Z-metabolite E as well
      as for the sex steroid hormones estradiol, estrone, testosterone,
      androstenedione, and progesterone. Plasma samples were subjected to protein
      precipitation followed by solid phase extraction. Upon derivatization with 3-[(N
      succinimide-1-yl)oxycarbonyl]-1-methylpyridinium iodide, all analytes were
      separated on a sub-2-MUm column with a gradient of acetonitrile in water with 0.1
      % of formic acid. Analytes were detected on a triple-quadrupole mass spectrometer
      with positive electrospray ionization in the multiple reaction monitoring mode.
      Our method demonstrated high sensitivity, accuracy, and precision. The lower
      limits of quantification were 12, 8, and 25 pM for bisphenol, E-metabolite E, and
      Z-metabolite E, respectively, and 4 pM for estradiol and estrogen, 50 pM for
      testosterone and androstenedione, and 25 pM for progesterone. The method was
      applied to plasma samples of postmenopausal patients taken at baseline and under
      tamoxifen therapy. Graphical Abstract Sample preparation and derivatization for
      highly sensitive quantification of estrogenic tamoxifen metabolites and steroid
      hormones by HPLC-MS/MS. 

PMID- 26206707
TI  - New derivatization strategies for the ultrasensitive analysis of non-aromatic
      analytes with APLI-TOF-MS.
AB  - Atmospheric pressure laser ionization (APLI) (Constapel et al. in Rapid Commun
      Mass Spectrom 19:326-336, 2005; Schiewek et al. in Anal Chem 79:4135-4140, 2007;
      Schmitz and Benter (2007) J Chromatography Library 72:89-114) is an ultra
      sensitive and selective ionization method for the determination of polycyclic
      aromatic compounds. The selectivity is an advantage but also a disadvantage. To
      overcome the limitation of APLI to aromatic compounds, we have already reported
      some derivatization strategies for common organic functional groups (Schiewek et
      al. in Angew Chem Int Ed 47:9989-9992, 2008). Here, we describe the synthesis of
      new APLI ionization labels and their use in new derivatization strategies. These
      new labels widen the range of APLI-(TOF)MS analysis to non-aromatic compounds
      with the most common functional groups such as amines, alcohols and carboxylic
      acids to gas chromatography (GC) and lower the limits of detection (LOD) down to
      concentrations as small as pmol/L and attomole on column. 

PMID- 26206708
TI  - Spatiotemporal neural network dynamics for the processing of dynamic facial
      expressions.
AB  - The dynamic facial expressions of emotion automatically elicit multifaceted
      psychological activities; however, the temporal profiles and dynamic interaction
      patterns of brain activities remain unknown. We investigated these issues using
      magnetoencephalography. Participants passively observed dynamic facial
      expressions of fear and happiness, or dynamic mosaics. Source-reconstruction
      analyses utilizing functional magnetic-resonance imaging data revealed higher
      activation in broad regions of the bilateral occipital and temporal cortices in
      response to dynamic facial expressions than in response to dynamic mosaics at 150
      200 ms and some later time points. The right inferior frontal gyrus exhibited
      higher activity for dynamic faces versus mosaics at 300-350 ms. Dynamic causal
      modeling analyses revealed that dynamic faces activated the dual visual routes
      and visual-motor route. Superior influences of feedforward and feedback
      connections were identified before and after 200 ms, respectively. These results
      indicate that hierarchical, bidirectional neural network dynamics within a few
      hundred milliseconds implement the processing of dynamic facial expressions. 

PMID- 26206709
TI  - Length of Time to Resolve Criminal Charges of Child Sexual Abuse: A Three-County
      Case Study.
AB  - The present study sought to examine the court culture of three Oregon counties
      and their timelines for resolving felony child sexual abuse cases. Specifically,
      we examined (a) case outcomes, churning (i.e., the extent to which four court
      events were rescheduled), the length of time to reach a criminal case resolution,
      and how this length of time compared to that for felonies generally; (b) whether
      mandatory minimum sentences affected resolution timeliness; and (c) key
      stakeholders' perceptions about their local court culture. Data included
      retrospective case-file abstraction (N = 532) on all felony child sex crimes for
      a 2-year period and interviews with legal professionals (N = 23). Across all
      three counties, a minority of child sexual abuse cases (18% to 47%) were resolved
      within the target timeframe of 4 months. In contrast, most felonies (65% to 77%)
      were resolved within this timeframe. The rescheduling of trials and the
      requirement of mandatory minimum sentences for some felony child sexual abuse
      crimes increased the time until case resolution. Results suggest that court
      cultures that are hierarchical and cooperative may lead to longer case resolution
      times than court cultures that are self-managing or autonomous. Implications of
      these results and other results are discussed.

PMID- 26206710
TI  - Cortical thickness differences in the prefrontal cortex in children and
      adolescents with ADHD in relation to dopamine transporter (DAT1) genotype.
AB  - Several lines of evidence suggest that the dopamine transporter gene (DAT1) plays
      a crucial role in attention deficit hyperactivity disorder (ADHD). Concretely,
      recent data indicate that the 10-repeat (10R) DAT1 allele may mediate
      neuropsychological functioning, response to methylphenidate, and even brain
      function and structure in children with ADHD. This study aimed to investigate the
      influence of 10R DAT1 on thickness of the prefrontal cortex in children and
      adolescents with ADHD. To this end, brain magnetic resonance images were acquired
      from 33 patients with homozygosity for the 10R allele and 30 patients with a
      single copy or no copy of the allele. The prefrontal cortex of each MRI scan was
      automatically parceled into regions of interest (ROIs) based on Brodmann areas
      (BA). The two groups were matched for age, gender, IQ, ADHD subtype, symptom
      severity, comorbidity and medication status. However, patients with two copies of
      the 10R allele exhibited significantly decreased cortical thickness in right BA
      46 relative to patients with one or fewer copies of the allele. No other
      prefrontal ROI differed significantly between the two groups. Present findings
      suggest that cortical thickness of right lateral prefrontal cortex (BA 46) is
      influenced by the presence of the DAT1 10 repeat allele in children and
      adolescents with ADHD. 

PMID- 26206711
TI  - Investigation and Management of a Rhizomucor Outbreak in a Pediatric Cancer
      Hospital in Egypt.
AB  - We describe an outbreak of mucormycosis in a pediatric oncology hospital during
      December 2010 and the measures taken to stop it. The outbreak began with two
      consecutive cases of laboratory-documented mucormycosis infections within 1 week.
      Investigations to track the source were conducted immediately. Air plate cultures
      from machines and ducts supplying patients' rooms revealed the growth of
      Rhizomucor. Of five affected patients, all had acute leukemia and three were
      histopathologically proven. All patients were treated with liposomal amphotericin
      B after mucormycosis was diagnosed. Posaconazole was used as a secondary
      prophylaxis in one case. Three patients died.

PMID- 26206712
TI  - Electrochemical fabrication and characterization of Cu/Cu2O multi-layered micro
      and nanorods in Li-ion batteries.
AB  - Electrodes composed of freestanding nano- and microrods composed of stacked
      layers of copper and cuprous oxide have been fabricated using a straightforward
      one-step template-assisted pulsed galvanostatic electrodeposition approach. The
      approach provided precise control of the thickness of each individual layer of
      the high-aspect-ratio rods as was verified by SEM, EDS, XRD, TEM and EELS
      measurements. Rods with diameters of 80, 200 and 1000 nm were deposited and the
      influence of the template pore size on the structure and electrochemical
      performance of the conversion reaction based electrodes in lithium-ion batteries
      was investigated. The multi-layered Cu2O/Cu nano- and microrod electrodes
      exhibited a potential window of more than 2 V, which was ascribed to the presence
      of a distribution of Cu2O (and Cu, respectively) nanoparticles with different
      sizes and redox potentials. As approximately the same areal capacity was obtained
      independent of the diameter of the multi-layered rods the results demonstrate the
      presence of an electroactive Cu2O layer with a thickness defined by the time
      domain of the measurements. It is also demonstrated that while the areal capacity
      of the electrodes decreased dramatically when the scan rate was increased from
      0.1 to 2 mV s(-1), the capacity remained practically constant when the scan rate
      was further increased to 100 mV s(-1). This behaviour can be explained by
      assuming that the capacity is limited by the lithium ion diffusion rate though
      the Cu2O layer generated during the oxidation step. The electrochemical
      performance of present type of 3-D multi-layered rods provides new insights into
      the lithiation and delithiation reactions taking place for conversion reaction
      materials such as Cu2O. 

PMID- 26206713
TI  - Trial design innovations: Clinical trials for treatment of neuropsychiatric
      symptoms in Alzheimer's Disease.
AB  - Neuropsychiatric symptoms are common in Alzheimer's disease (AD) and other
      neurodegenerative disorders. Recent progress has been made with clinical trials,
      advancing new therapies for psychosis in Parkinson's disease (PD), agitation in
      AD, and apathy in AD. Definitions have emerged for agitation and apathy in
      patients with cognitive impairment, facilitating recruitment of clinical trial
      populations. Progress in clinical trial design and the agents being assessed
      promise to advance therapies for disabling symptoms and improve quality of life
      for patients and caregivers. 

PMID- 26206714
TI  - An endoscopic structured light system using multispectral detection.
AB  - PURPOSE: In clinical examinations, the tissue surface topology is an important
      feature for detecting the tissue pathology and implementing augmented reality. We
      have previously presented a miniaturised structured light (SL) system for
      recovery of tissue surface shape in minimally invasive surgery (MIS), based on a
      flexible multispectral structured illumination probe (1.9 mm diameter) (Clancy et
      al. in Biomed Opt Express 2(11):3119-3128, 2011. doi: 10.1364/BOE.2.003119 ).
      This paper reports further hardware and analytical developments to improve the
      light pattern decoding result and increase the reconstruction accuracy. METHODS:
      The feasibility of using an 8-band multispectral camera with higher pattern
      colour discrimination ability than normal RGB camera in this system was studied.
      Additionally, the "normalised cut" algorithm was investigated to improve pattern
      segmentation. RESULTS: The whole SL system was evaluated by phantom and in vivo
      experiments. Higher pattern identification performance than that of an RGB camera
      was recorded by using the multispectral camera (average precision >97%, average
      sensitivity >62%). An average of [Formula: see text] reconstruction error was
      achieved using the proposed pattern decoding method on a heart phantom at a
      working distance of approximately 10 cm. CONCLUSIONS: The experiment showed the
      superiority of the multispectral camera over the RGB camera in the spot
      identification step. The proposed pattern decoding algorithm underwent
      evaluations using different experiments, showing that it provided promising
      reconstruction results. The potential of using this system in MIS environments
      has been demonstrated.

PMID- 26206715
TI  - Supervised machine learning-based classification scheme to segment the brainstem
      on MRI in multicenter brain tumor treatment context.
AB  - PURPOSE: To constrain the risk of severe toxicity in radiotherapy and
      radiosurgery, precise volume delineation of organs at risk is required. This task
      is still manually performed, which is time-consuming and prone to observer
      variability. To address these issues, and as alternative to atlas-based
      segmentation methods, machine learning techniques, such as support vector
      machines (SVM), have been recently presented to segment subcortical structures on
      magnetic resonance images (MRI). METHODS: SVM is proposed to segment the
      brainstem on MRI in multicenter brain cancer context. A dataset composed by 14
      adult brain MRI scans is used to evaluate its performance. In addition to spatial
      and probabilistic information, five different image intensity values (IIVs)
      configurations are evaluated as features to train the SVM classifier.
      Segmentation accuracy is evaluated by computing the Dice similarity coefficient
      (DSC), absolute volumes difference (AVD) and percentage volume difference between
      automatic and manual contours. RESULTS: Mean DSC for all proposed IIVs
      configurations ranged from 0.89 to 0.90. Mean AVD values were below 1.5 cm(3),
      where the value for best performing IIVs configuration was 0.85 cm(3),
      representing an absolute mean difference of 3.99% with respect to the manual
      segmented volumes. CONCLUSION: Results suggest consistent volume estimation and
      high spatial similarity with respect to expert delineations. The proposed
      approach outperformed presented methods to segment the brainstem, not only in
      volume similarity metrics, but also in segmentation time. Preliminary results
      showed that the approach might be promising for adoption in clinical use.

PMID- 26206716
TI  - Concentrating carbohydrates before sleep improves feeding regulation and
      metabolic and inflammatory parameters in mice.
AB  - New evidance highlights the importance of food timing. Recently, we showed that a
      low-calorie diet with carbohydrates eaten mostly at dinner changed diurnal
      hormone secretion and led to greater weight loss and improved metabolic status in
      obese people. Herein, we set out to test whether concentrated-carbohydrates diet
      (CCD), in which carbohydrates are fed only before sleep, leads to an improved
      metabolic status in mouse hypothalamus and peripheral tissues. Diet-induced obese
      mice were given concentrated or distributed carbohydrate diet for 6 weeks. Obese
      mice fed CCD ate 8.3% less, were 9.3% leaner and had 39.7% less fat mass. Leptin,
      ghrelin and adiponectin displayed altered secretion. In addition, these mice
      exhibited an improved biochemical and inflammatory status. In the hypothalamus,
      anorexigenic signals were up-regulated and orexigenic signals were down
      regulated. In peripheral tissues, CCD promoted adiponectin signaling, repressed
      gluconeogenesis, enhanced lipid oxidation and lowered inflammation, thus
      ameliorating the major risk factors of obesity. 

PMID- 26206717
TI  - Estrogen-Related Receptors and the control of bone cell fate.
AB  - Bone loss is naturally occurring in aging males and females and exacerbated in
      the latter after menopause, altogether leading to cumulative skeleton fragility
      and increased fracture risk. Two types of therapeutic strategies can be
      envisioned to counteract age- or menopause-associated bone loss, aiming at either
      reducing bone resorption exerted by osteoclasts or, alternatively, promoting bone
      formation by osteoblasts. We here summarize data suggesting that inhibition of
      the Estrogen-Related Receptors alpha and/or gamma could promote bone formation
      and compensate for bone loss induced by ageing or estrogen-deficiency.

PMID- 26206719
TI  - A multicenter photoprovocation study to identify potential biomarkers by global
      peptide profiling in cutaneous lupus erythematosus.
AB  - Cutaneous lupus erythematosus (CLE) is an inflammatory autoimmune skin disease in
      which abnormal photosensitivity is an important pathogenetic factor but is
      difficult to predict, creating a challenge in determining treatment efficacy.
      Although photosensitivity in CLE patients may change over time, photoprovocation
      testing with ultraviolet (UV) A and UVB irradiation can be a helpful tool to
      explore differences between responders and nonresponders during photoprovocation.
      To identify biomarkers that could substitute for the clinical endpoint lesion
      development, we performed a global peptidomics profiling analysis of CLE subjects
      in a controlled photoprovocation study. Plasma and skin biopsy samples were
      collected before and after UV-irradiation from 13 healthy volunteers and 47 CLE
      subjects. Twenty-two of the 47 CLE subjects developed skin lesions. The samples
      were analyzed using a label-free quantitative peptidomics workflow combined with
      univariate and multivariate statistical analyses. The primary finding was
      identification of a specific plasma peptide signature separating responders
      versus nonresponders at baseline. The peptide signature consisted of beta 2
      microglobulin (B2MG), human beta-defensin-1, and peptides derived from CD99,
      polymeric immunoglobulin receptor, and immunoglobulin kappa light chains. In
      skin, elevated B2MG levels correlated with lesion formation. Our results show
      that the peptidome is a rich source of potential biomarkers for predicting
      photosensitivity in CLE. 

PMID- 26206718
TI  - DGCR8 is essential for tumor progression following PTEN loss in the prostate.
AB  - In human prostate cancer, the microRNA biogenesis machinery increases with
      prostate cancer progression. Here, we show that deletion of the Dgcr8 gene, a
      critical component of this complex, inhibits tumor progression in a Pten-knockout
      mouse model of prostate cancer. Early stages of tumor development were
      unaffected, but progression to advanced prostatic intraepithelial neoplasia was
      severely inhibited. Dgcr8 loss blocked Pten null-induced expansion of the basal
      like, but not luminal, cellular compartment. Furthermore, while late-stage Pten
      knockout tumors exhibit decreased senescence-associated beta-galactosidase
      activity and increased proliferation, the simultaneous deletion of Dgcr8 blocked
      these changes resulting in levels similar to wild type. Sequencing of small RNAs
      in isolated epithelial cells uncovered numerous miRNA changes associated with
      PTEN loss. Consistent with a Pten-Dgcr8 association, analysis of a large cohort
      of human prostate tumors shows a strong correlation between Akt activation and
      increased Dgcr8 mRNA levels. Together, these findings uncover a critical role for
      microRNAs in enhancing proliferation and enabling the expansion of the basal cell
      compartment associated with tumor progression following Pten loss.

PMID- 26206720
TI  - Phase I study of concurrent vinorelbine and radiation therapy in high-risk
      postmastectomy breast cancer patients.
AB  - BACKGROUND: Postmastectomy chest wall irradiation is recommended for high-risk
      breast cancer patients, such as those with >=4 positive nodes. Irradiation is
      performed sequentially rather than concurrently with chemotherapy. However, the 5
      year locoregional recurrence-free survival was statistically better in the
      concurrent method in node-positive patients in a prior study. The benefit of
      concurrent chemoradiotherapy for postmastectomy breast cancer patients is
      uncertain. Vinorelbine is often used as concurrent chemoradiotherapy for non
      small cell lung cancer in Japan and has antitumor activity in breast cancer as
      well. Thus, we planned this dose-finding study of concurrent vinorelbine and
      radiation therapy in high-risk postmastectomy breast cancer patients. METHODS:
      High-risk postmastectomy breast cancer patients were recruited. Patients received
      weekly vinorelbine administered concurrently with radiation therapy. The
      radiation dose was 50 Gy in 25 fractions over 5 weeks. Vinorelbine was
      administered weekly without a break, so the maximum number of vinorelbine cycles
      was five. A 3 + 3 dose-escalation design was used for determining maximal
      tolerable dose, recommended dose and safety. RESULTS: A total of 10 patients were
      enrolled in cohorts of 10 and 15 mg/m(2). Dose-limiting toxicity was observed in
      one case in 10 mg/m(2) and two cases in 15 mg/m(2). Therefore, the maximal
      tolerable dose was defined at 15 mg/m(2) and the recommended dose was determined
      at 10 mg/m(2). The main adverse events included radiation dermatitis and
      neutropenia. Recurrence was observed in one patient with a median follow-up of 40
      months. CONCLUSIONS: Concurrent vinorelbine and radiation therapy has a
      manageable safety profile at 10 mg/m(2) in high-risk postmastectomy breast cancer
      patients.

PMID- 26206721
TI  - Greater Volume of Acute Normovolemic Hemodilution May Aid in Reducing Blood
      Transfusions After Cardiac Surgery.
AB  - BACKGROUND: Perioperative red blood cell transfusions (RBC) are associated with
      increased morbidity and mortality after cardiac surgery. Acute normovolemic
      hemodilution (ANH) is recommended to reduce perioperative transfusions; however,
      supporting data are limited and conflicting. We describe the relationship between
      ANH and RBC transfusions after cardiac surgery using a multi-center registry.
      METHODS: We analyzed 13,534 patients undergoing cardiac surgery between 2010 and
      2014 at any of the 26 hospitals participating in a prospective cardiovascular
      perfusion database. The volume of ANH (no ANH, <400 mL, 400 to 799 mL, >= 800 mL)
      was recorded and linked to each center's surgical data. We report adjusted
      relative risks reflecting the association between the use and amount of ANH and
      the risk of perioperative RBC transfusion. Results were adjusted for preoperative
      risk factors, procedure, body surface area, preoperative hematocrit, and center.
      RESULTS: The ANH was used in 17% of the patients. ANH was associated with a
      reduction in RBC transfusions (RRadj [adjusted risk ratio] 0.74, p < 0.001).
      Patients having 800 mL or greater of ANH had the most profound reduction in RBC
      transfusions (RRadj 0.57, p < 0.001). Platelet and plasma transfusions were also
      significantly lower with ANH. The ANH population had superior postoperative
      morbidity and mortality compared with the no ANH population. CONCLUSIONS: There
      is a significant association between ANH and reduced perioperative RBC
      transfusion in cardiac surgery. Transfusion reduction is most profound with
      larger volumes of ANH. Our findings suggest the volume of ANH, rather than just
      its use, may be an important feature of a center's blood conservation strategy.

PMID- 26206722
TI  - Myocardial Infarction Classification on Outcomes in Nonemergent Coronary Artery
      Bypass Grafting.
AB  - BACKGROUND: Although patients with ST elevation myocardial infarctions (STEMIs)
      are known to have worse outcomes than patients with non-ST elevation myocardial
      infarctions (NSTEMIs), such differences are not well described in the subset of
      patients undergoing coronary artery bypass grafting. The purpose of this study is
      to compare postoperative outcomes of patients undergoing nonemergent coronary
      artery bypass grafting within 1 week after an STEMI versus NSTEMI. METHODS: A
      retrospective study was performed on patients undergoing isolated coronary artery
      bypass grafting between 1 and 7 days from an MI from 2008 to 2012. Postoperative
      outcomes, including mortality and composite postoperative morbidity for patients
      with STEMI versus NSTEMI, were compared within each group. RESULTS: Of the 446
      patients undergoing nonemergent isolated coronary artery bypass grafting between
      1 and 7 days after an MI, 122 patients (27.3%) had an STEMI. The STEMI cohort was
      younger with less incidence of hypertension than the NSTEMI cohort. However,
      aside from having a lower incidence of congestive heart failure, STEMI patients
      had an overall poorer cardiac status than NSTEMI patients. No differences were
      found in mortality, rates of major complication, length of intensive care unit
      stay, and length of hospital stay between STEMI and NSTEMI patients. CONCLUSION:
      Despite differences in preoperative characteristics and pathophysiology of
      patients undergoing coronary artery bypass grafting between 1 and 7 days after
      NSTEMI versus STEMI, no difference was found in early surgical outcome. The
      classification of MI should therefore not influence surgical decision making in
      such patients.

PMID- 26206723
TI  - Bat-to-human: spike features determining 'host jump' of coronaviruses SARS-CoV,
      MERS-CoV, and beyond.
AB  - Both severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East
      respiratory syndrome coronavirus (MERS-CoV) are zoonotic pathogens that crossed
      the species barriers to infect humans. The mechanism of viral interspecies
      transmission is an important scientific question to be addressed. These
      coronaviruses contain a surface-located spike (S) protein that initiates
      infection by mediating receptor-recognition and membrane fusion and is therefore
      a key factor in host specificity. In addition, the S protein needs to be cleaved
      by host proteases before executing fusion, making these proteases a second
      determinant of coronavirus interspecies infection. Here, we summarize the
      progress made in the past decade in understanding the cross-species transmission
      of SARS-CoV and MERS-CoV by focusing on the features of the S protein, its
      receptor-binding characteristics, and the cleavage process involved in priming. 

PMID- 26206725
TI  - Proposed human stratum corneum water domain in chemical absorption.
AB  - Compounds with varying physical and chemical properties may have different
      affinities to the stratum corneum (SC) and/or its intercellular lipids, keratin
      protein, and possible water domains. To better understand the mechanism of
      percutaneous absorption, we utilized 21 carbon-14 labeled chemicals, with wide
      hydrophilicity (log P = -0.05 to 6.17), and quantified their
      absorption/adsorption properties for a short incubation time (15 min) with
      regards to intact SC membrane, delipidized SC membrane and SC lipid. A facile
      method was developed for SC/lipid absorption, providing a more equivalent
      procedure and comparable data. SC lipid absorption of chemical solutes positively
      correlated with the octanol/water partition coefficient (log P). Differences
      between the percent dose of chemical absorption to intact SC and the total
      percent dose contributed by the protein and lipid domains suggest the possibility
      and significance of a water domain. Absorption rate experiments showed a longer
      lag time for intact SC than for delipidized SC or SC lipid, suggesting that the
      water domain may delay chemical binding to protein and lipid domains, and may be
      a factor in the resistance of many chemicals to current decontamination methods.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26206724
TI  - Stress, Sleep and Recovery in Elite Soccer: A Critical Review of the Literature.
AB  - In elite soccer, players are frequently exposed to various situations and
      conditions that can interfere with sleep, potentially leading to sleep
      deprivation. This article provides a comprehensive and critical review of the
      current available literature regarding the potential acute and chronic stressors
      (i.e., psychological, sociological and physiological stressors) placed on elite
      soccer players that may result in compromised sleep quantity and/or quality.
      Sleep is an essential part of the recovery process as it provides a number of
      important psychological and physiological functions. The effects of sleep
      disturbance on post-soccer match fatigue mechanisms and recovery time course are
      also described. Physiological and cognitive changes that occur when competing at
      night are often not conducive to sleep induction. Although the influence of high
      intensity exercise performed during the night on subsequent sleep is still
      debated, environmental conditions (e.g., bright light in the stadium, light
      emanated from the screens) and behaviours related to evening soccer matches
      (e.g., napping, caffeine consumption, alcohol consumption) as well as engagement
      and arousal induced by the match may all potentially affect subsequent sleep.
      Apart from night soccer matches, soccer players are subjected to inconsistency in
      match schedules, unique team schedules and travel fatigue that may also
      contribute to the sleep debt. Sleep deprivation may be detrimental to the outcome
      of the recovery process after a match, resulting in impaired muscle glycogen
      repletion, impaired muscle damage repair, alterations in cognitive function and
      an increase in mental fatigue. The role of sleep in recovery is a complex issue,
      reinforcing the need for future research to estimate the quantitative and
      qualitative importance of sleep and to identify influencing factors. Efficient
      and individualised solutions are likely needed.

PMID- 26206726
TI  - Intrinsic carnosine metabolism in the human kidney.
AB  - Histidine-containing dipeptides like carnosine and anserine have protective
      functions in both health and disease. Animal studies suggest that carnosine can
      be metabolized within the kidney. The goal of this study was to obtain evidence
      of carnosine metabolism in the human kidney and to provide insight with regards
      to diabetic nephropathy. Expression, distribution, and localization of
      carnosinase-1 (CNDP1), carnosine synthase (CARNS), and taurine transporters
      (TauT) were measured in human kidneys. CNDP1 and CARNS activities were measured
      in vitro. CNDP1 and CARNS were located primarily in distal and proximal tubules,
      respectively. Specifically, CNDP1 levels were high in tubular cells and podocytes
      (20.3 +/- 3.4 and 15 +/- 3.2 ng/mg, respectively) and considerably lower in
      endothelial cells (0.5 +/- 0.1 ng/mg). CNDP1 expression was correlated with the
      degradation of carnosine and anserine (r = 0.88 and 0.81, respectively). Anserine
      and carnosine were also detectable by HPLC in the renal cortex. Finally, TauT
      mRNA and protein were found in all renal epithelial cells. In diabetic patients,
      CNDP1 seemed to be reallocated to proximal tubules. We report compelling evidence
      that the kidney has an intrinsic capacity to metabolize carnosine. Both CNDP1 and
      CARNS are expressed in glomeruli and tubular cells. Carnosine-synthesizing and
      carnosine-hydrolyzing enzymes are localized in distinct compartments in the
      nephron and increased CNDP1 levels suggest a higher CNDP1 activity in diabetic
      kidneys.

PMID- 26206728
TI  - First Reported Case of Unexpected Response to an Epidermal Growth Factor Receptor
      Tyrosine Kinase Inhibitor in the I744M Uncommon EGFR Mutation.

PMID- 26206727
TI  - beta-Alanine supplementation and military performance.
AB  - During sustained high-intensity military training or simulated combat exercises,
      significant decreases in physical performance measures are often seen. The use of
      dietary supplements is becoming increasingly popular among military personnel,
      with more than half of the US soldiers deployed or garrisoned reported to using
      dietary supplements. beta-Alanine is a popular supplement used primarily by
      strength and power athletes to enhance performance, as well as training aimed at
      improving muscle growth, strength and power. However, there is limited research
      examining the efficacy of beta-alanine in soldiers conducting operationally
      relevant tasks. The gains brought about by beta-alanine use by selected
      competitive athletes appears to be relevant also for certain physiological
      demands common to military personnel during part of their training program.
      Medical and health personnel within the military are expected to extrapolate and
      implement relevant knowledge and doctrine from research performed on other
      population groups. The evidence supporting the use of beta-alanine in competitive
      and recreational athletic populations suggests that similar benefits would also
      be observed among tactical athletes. However, recent studies in military
      personnel have provided direct evidence supporting the use of beta-alanine
      supplementation for enhancing combat-specific performance. This appears to be
      most relevant for high-intensity activities lasting 60-300 s. Further, limited
      evidence has recently been presented suggesting that beta-alanine supplementation
      may enhance cognitive function and promote resiliency during highly stressful
      situations.

PMID- 26206729
TI  - Shocking therapy: Brief electrical stimulation for delayed nerve repair.
AB  - This commentary provides perspective on a recent paper published in Experimental
      Neurology by Elzinga et al. where the authors investigated the effect of brief
      electrical stimulation (ES) on nerve regeneration after delayed nerve repair in a
      rodent model. Their results from a well controlled series of experiments
      indicated that brief ES promoted axonal outgrowth after chronic axotomy as well
      after chronic Schwann cell and muscle denervation. ES also increased chronically
      axotomized neurons regenerating into chronically denervated stumps, which
      represent a true delayed repair. The authors conclude that brief ES promotion of
      nerve regeneration after delayed nerve repair is as effective as after immediate
      repair. Given the prior experimental evidence, and the prior clinical data from
      patients with carpal tunnel syndrome and digital nerve repair, the implication of
      this new work is to consider a well designed clinical trial for use of brief ES
      in nerve graft and nerve transfer repairs. 

PMID- 26206730
TI  - Diversity, abundance, and evolutionary dynamics of Pong-like transposable
      elements in Triticeae.
AB  - Pong-like elements are members of the PIF/Harbinger superfamily of DNA
      transposons that has been described in many plants, animals, and fungi. Most Pong
      elements contain two open reading frames (ORFs). One encodes a transposase (ORF2)
      that catalyzes transposition of Pong and related non-autonomous elements, while
      the function of the second is unknown. Little is known about the evolutionary
      history of Pong elements in flowering plants. In this work, we present the first
      comprehensive analysis of the diversity, abundance, and evolution of the Pong
      like transposase gene in the genomes of 21 diploid species from the wheat tribe,
      Triticeae, and we present the first convincing evidence of horizontal transfer of
      nuclear-encoded Pong elements in any organism. A phylogenetic analysis of nearly
      300 Pong sequences based on a conserved region of the transposase domain revealed
      a complex evolutionary history of Pong elements that can be best explained by
      ancestral polymorphism, followed by differential evolutionary success of some
      transposase lineages, and by occasional horizontal transfer between
      phylogenetically distant genera. In addition, we used transposon display to
      estimate the abundance of the transposase gene within Triticeae genomes, and our
      results revealed varying levels of Pong proliferation, with numbers of
      transposase copies ranging from 22 to 92. Comparisons of Pong transposase
      abundance to flow cytometry estimates of genome size revealed that larger
      Triticeae genome size was not correlated with transposase abundance. 

PMID- 26206731
TI  - Rogue waves lead to the instability in GaN semiconductors.
AB  - A new approach to understand the electron/hole interfaced plasma in GaN high
      electron mobility transistors (HEMTs). A quantum hydrodynamic model is
      constructed to include electrons/holes degenerate pressure, Bohm potential, and
      the exchange/correlation effect and then reduced to the nonlinear Schrodinger
      equation (NLSE). Numerical analysis of the latter predicts the rough
      (in)stability domains, which allow for the rogue waves to occur. Our results
      might give physical solution rather than the engineering one to the intrinsic
      problems in these high frequency/power transistors. 

PMID- 26206732
TI  - Intensity modulated radiation therapy with simultaneous integrated boost in early
      breast cancer irradiation. Report of feasibility and preliminary toxicity.
AB  - PURPOSE: To investigate the feasibility and tolerance in the use of adjuvant
      intensity modulated radiation therapy (IMRT) and simultaneous integrated boost in
      patients with a diagnosis of breast cancer after breast-conserving surgery.
      PATIENTS AND METHODS: Between September 2011 to February 2013, 112 women with a
      diagnosis of early breast cancer (T1-2, N0-1, M0) were treated with IMRT and
      simultaneous integrated boost after breast-conserving surgery in our institution.
      A dose of 50Gy in 25 fractions was prescribed to the whole breast and an
      additional dose of radiation was prescribed on the tumour bed. A dose
      prescription of 60Gy in 25 fractions to the tumour bed was used in patients with
      negative margins after surgery, whereas if the margins were close (<1mm) or
      positive (without a new surgical resection) a dose of 64Gy was prescribed. All
      patients were followed with periodic clinical evaluation. Acute and late toxicity
      were scored using the EORTC/RTOG radiation morbidity score system. Both patient
      and physician recorded cosmetic outcome evaluation with a subjective judgment
      scale at the time of scheduled follow-up. RESULTS: The median follow-up was 28
      months (range 24-40 months). The acute skin grade toxicity during the treatment
      was grade 0 in 8 patients (7%), grade 1 in 80 (72%), grade 2 in 24 cases (21%).
      No grade 3 or higher acute skin toxicity was observed. At 12 months, skin
      toxicity was grade 0 in 78 patients (70%), grade 1 in 34 patients (30%). No
      toxicity grade 2 or higher was registered. At 24 months, skin toxicity was grade
      0 in 79 patients (71%), grade 1 in 33 patients (29%). No case of grade 2 toxicity
      or higher was registered. The pretreatment variables correlated with skin grade 2
      acute toxicity were adjuvant chemotherapy (P=0.01) and breast volume >=700cm(3)
      (P=0.001). Patients with an acute skin toxicity grade 2 had a higher probability
      to develop late skin toxicity (P<0.0001). In the 98% of cases, patients were
      judged to have a good or excellent cosmetic outcome. The 2-year-overall survival
      and 2-year-local control were 100%. CONCLUSION: These data support the
      feasibility and safety of IMRT with simultaneous integrated boost in patients
      with a diagnosis of early breast cancer following breast-conserving surgery with
      acceptable acute and late treatment-related toxicity. A longer follow-up is
      needed to define the efficacy on outcomes.

PMID- 26206733
TI  - [Interobserver variability study for daily cone beam computed tomography
      registration of prostate volumetric modulated arc therapy].
AB  - PURPOSE: This work evaluated the interobserver variability in cone beam computed
      tomography (CBCT) registration for prostate cancers treated with intensity
      modulated radiotherapy. MATERIAL AND METHODS: Twelve technologists realized 286
      CBCT/CT registrations (bone registration followed by prostate to prostate
      registration). The registration results were compared to those obtained by two
      radiation oncologists (reference). Each technologist reported the shifts
      calculated by the software in all three axes. A statistical analysis allowed us
      to calculate the minimum threshold under which 95% of the observers found similar
      values. A variance analysis followed by the post hoc test were used to find
      differences in interobserver registration variability and determine whether any
      individual users performed registrations which differed significantly from those
      of the other users. RESULTS: The registration differences compared to the
      reference in the three directions in terms of 95th percentile are: 2.1mm left
      right, 3.5mm target-gun, 7.3mm anterior-posterior. In the posterior direction, 4%
      of the observers have found differences superior to 8mm, margin used in routine
      without the use of a daily CBCT. The variance test revealed a P-value <0.05 only
      for target-gun and for all observers there was no significant difference compared
      to the reference. CONCLUSION: This study confirmed the interest of a 3D tissue
      registration for prostate treatments. The registration study showed a good
      interobserver reproducibility. This showed the importance of a daily CBCT/CT
      registration in prostate treatment with the possibility of a planning target
      volume margin reduction in the three directions. An evaluation of a partial
      delegation of registration to technologists should be done by the radiation
      oncologists.

PMID- 26206734
TI  - Adverse Prenatal, Perinatal and Neonatal Experiences in Children with Anxiety
      Disorders.
AB  - This study examined the incidence of adverse prenatal, perinatal, and neonatal
      experiences amongst children with anxiety disorders, and the relationship to
      clinical symptomology and functional impairment in treatment-seeking children (N
      = 107) with a primary anxiety disorder. Anxious children had higher rates of
      reported maternal prescription medication use during pregnancy, maternal smoking
      and illness during pregnancy and neonatal complications (including neonatal
      intensive care and feeding issues) compared with population base rates and non
      affected children. Almost one-third had early problems with sleep. Developmental
      problems were common with more than half having at least one area of delay. More
      than three quarters of anxious children had a first-degree family member with a
      psychiatric history. There were several associations between neonatal
      complications and subsequent clinical symptomology, including attention deficit
      hyperactivity disorder and depressive comorbidity, anxiety severity and
      functional impairment. Findings suggest higher rates of perinatal complications
      in anxious children. 

PMID- 26206735
TI  - Childhood Adversity, Timing of Puberty and Adolescent Depressive Symptoms: A
      Longitudinal Study in Taiwan.
AB  - Childhood adversity contributes to depressive symptoms in adolescence, but far
      less research has focused on an Asian context. This study aims to identify the
      long-term impact of childhood adversity on adolescents' depressive symptoms and
      whether this association is moderated by gender and early pubertal timing in
      Taiwan. Data in this study are from the Taiwan Education Panel Survey, a
      longitudinal study that surveyed and followed 4261 junior high school students in
      year 2001 (at age 13) and three more waves (at ages 15, 17, and 18). Conditional
      latent growth model results show that having adversity is positively associated
      with the intercept, but negatively associated with the linear trend of changes of
      depressive symptoms in adolescence (p < .01). Early pubertal timing is only
      positively associated with baseline levels for boys (p < .01). Both adversity and
      early pubertal timing contributes to depressive symptoms when adolescents start
      junior high school.

PMID- 26206736
TI  - Individual and Combined Risk Factors for Incident Atrial Fibrillation and
      Incident Stroke: An Analysis of 3 Million At-Risk US Patients.
AB  - BACKGROUND: The incremental effects of risk factor combinations for atrial
      fibrillation (AF) and stroke are incompletely understood. We sought to quantify
      the risks of incident AF and stroke for combinations of established risk factors
      in a large US sample. METHODS AND RESULTS: Patients with no evidence of AF or
      stroke in 2007 were stratified by combinations of the following risk factors:
      heart failure, hypertension, diabetes, age 65 to 74, age >=75, coronary artery
      disease, and chronic kidney disease. Patients with >=2 of the first 5 or >=3 of
      the first 7, classified as "high-risk," and an age-matched sample of patients
      with fewer risk factors, classified as "low-risk," were followed over 2008-2010
      for incident AF and stroke. Annualized incidence rates and risks were quantified
      for each combination of factors by using Cox regression. Annualized incidence
      rates for AF, stroke, and both were 3.59%, 3.27%, and 0.62% in 1 851 653 high
      risk patients and 1.32%, 1.48%, and 0.18% in 1 156 221 low-risk patients,
      respectively. Among patients with 1 risk factor, those with age >=75 had the
      highest hazards of incident AF and stroke (HR 9.2, 6.9). Among patients with 2
      risk factors, those with age >=75 and heart failure had the highest annualized
      incidence rates of AF and stroke (10.2%, 5.9%). The combination of age >=75 and
      hypertension was prevalent and had the highest incidences of AF and stroke.
      CONCLUSIONS: Adults with combinations of known risk factors are at increased risk
      of incident AF and stroke, but combinations of risk factors are not always
      additive.

PMID- 26206737
TI  - Very Low Ventricular Pacing Rates Can Be Achieved Safely in a Heterogeneous
      Pacemaker Population and Provide Clinical Benefits: The CANadian Multi-Centre
      Randomised Study-Spontaneous AtrioVEntricular Conduction pReservation (CAN-SAVE
      R) Trial.
AB  - BACKGROUND: It is well recognized that right ventricular apical pacing can have
      deleterious effects on ventricular function. We performed a head-to-head
      comparison of the SafeR pacing algorithm versus DDD pacing with a long
      atrioventricular delay in a heterogeneous population of patients with dual
      chamber pacemakers. METHODS AND RESULTS: In a multicenter prospective double
      blinded randomized trial conducted at 10 centers in Canada, 373 patients, age
      71+/-11 years, with indications for dual chamber DC pacemakers were randomized
      1:1 to SafeR or DDD pacing with a long atrioventricular delay (250 ms). The
      primary objective was twofold: (1) reduction in the proportion of ventricular
      paced beats at 1 year; and (2) impact on atrial fibrillation burden at 3 years,
      defined as the ratio between cumulative duration of mode-switches divided by
      follow-up time. Statistical significance of both co-primary end points was
      required for the trial to be considered positive. At 1 year of follow-up, the
      median proportion of ventricular-paced beats was 4.0% with DDD versus 0% with
      SafeR (P<0.001). At 3 years of follow-up, the atrial fibrillation burden was not
      significantly reduced with SafeR versus DDD (median 0.00%, interquartile range
      [0.00% to 0.23%] versus median 0.01%, interquartile range [0.00% to 0.44%],
      respectively, P=0.178]), despite a persistent reduction in the median proportion
      of ventricular-paced beats (10% with DDD compared to 0% with SafeR). CONCLUSIONS:
      A ventricular-paced rate <1% was safely achieved with SafeR in a population with
      a wide spectrum of indications for dual-chamber pacing. However, the lower
      percentage of ventricular pacing did not translate into a significant reduction
      in atrial fibrillation burden. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov/ Unique identifier: NCT01219621.

PMID- 26206740
TI  - Synergistic behaviour of ionic liquid impregnated sulphate-crosslinked chitosan
      towards adsorption of Cr(VI).
AB  - Aliquat-336 (an ionic liquid) impregnated sulphate-crosslinked chitosan (SCC) was
      prepared for escalating the adsorption of hexavalent chromium through concurrent
      interaction. The compound obtained was intensively characterized using Fourier
      transform infra red (FT-IR), X-ray diffraction (XRD), Scanning electron
      microscopic (SEM) and Energy dispersive X-ray (EDX) studies. Various isotherm
      studies have been carried out to understand the adsorption mechanism.
      Quantitative adsorption of Cr(VI) was observed at pH 3.0 with adsorption capacity
      of 250.90 mg g(-1) in accordance with Langmuir isotherm. The adsorption of Cr(VI)
      followed pseudo-second-order kinetics. The adsorption efficiency was found to
      decrease with increase in temperature due to increased randomness at interaction
      sites. The adsorption process was found to be exothermic and spontaneous in
      nature. Column studies were carried out to understand the applicability of the
      material for higher sample volumes. The adsorbent could be regenerated using
      sodium hydroxide treatment and the regenerated adsorbent had same efficiency
      towards adsorption of Cr(VI) as that of the original.

PMID- 26206738
TI  - Serum Mimecan Is Associated With Arterial Stiffness in Hypertensive Patients.
AB  - BACKGROUND: Mimecan plays an important role in endothelial and vascular smooth
      muscle cell integrity and may be involved the pathology of arterial stiffness.
      However, the role of mimecan in arterial stiffness in patients with hypertension
      is not well defined. METHODS AND RESULTS: A total of 116 hypertension patients
      and 54 healthy controls were enrolled in the investigation. Hypertensive patients
      were divided into 2 groups: the with arterial stiffness group (brachial-ankle
      pulse wave velocity [baPWV] >=1400 cm/s; n=83) and the without arterial stiffness
      group (baPWV <1400 cm/s; n=33). A noninvasive measure of vascular stiffness was
      performed using pulse wave velocity (PWV) measurement of baPWV. Hypertensive
      patients had higher baPWV, mimecan, and endothelin 1 (ET-1) than healthy
      controls. The arterial stiffness group had higher mimecan and endothelin 1 (ET-1)
      and lower ankle-brachial pressure index (ABI) than those without stiffness. In
      hypertensive patients, mimecan was inversely correlated with ABI (P<0.05) and
      positively correlated with baPWV, ET-1, and total cholesterol. On multivariable
      logistic regression analysis, diastolic blood pressure, mimecan, ET-1, and
      creatinine were independent predictors of arterial stiffness in hypertensive
      patients (P<0.05). CONCLUSIONS: Mimecan levels are higher in hypertensive
      patients than in healthy controls. Increased plasma mimecan levels are
      independently associated with increased arterial stiffness as assessed by baPWV.

PMID- 26206739
TI  - Binding and stabilisation effects of glycodendritic compounds with peanut
      agglutinin.
AB  - A number of new polyhydroxy-dendritic structures have been constructed from a few
      basic modules. The cores were derived from N
      tert(butyloxycarbonyl)tris[(propargyloxy)methyl]aminomethane, N,N'-bis-1,3-(tris
      (propargyloxymethyl)methyl)-5-(hydroxymethyl)isophthalamide, and N,N',N"-tris
      1,3,5-(tris-(propargyloxymethyl)methyl)-1,3,5-benzene tricarboxamide while the
      terminal groups were derived from beta-azido-galactose and beta-azido-lactose
      leading to six new glycodendrimeric compounds with up to 63 hydroxyl groups on
      the periphery. The binding ability of the new compounds to peanut agglutinin
      (PNA), a galactose recognizing lectin from Arachis hypogaea, was investigated by
      nano-Isothermal Titration Calorimetry and nano-Differential Scanning Calorimetry.
      We found that the compounds had stronger stabilising effect on the macromolecules
      compared to the corresponding sugars. The interaction between lectin and the
      glycodendrimeric unit is entropically driven with only a low enthalpic
      contribution. A trend was found with increasing number of carbohydrates that is
      strongly influenced by the steric constraints of the ligands. Our results
      indicate the significance of multivalency and size control in the successful
      design of lectin inhibitors. 

PMID- 26206741
TI  - Characterization of poly-3-hydroxybutyrate (PHB) produced from Ralstonia eutropha
      using an alkali-pretreated biomass feedstock.
AB  - Alkaline pretreatment using NaOH, KOH, or NaOCl has been applied to various types
      of waste biomass to enhance enzymatic digestibility. Pretreatment (2% NaOH, 121 
      degrees C, 30 min) of rice paddy straw (PS) resulted in a maximum yield of 703 mg
      of reducing sugar per gram of PS with 84.19% hydrolysis yield after a two-step
      enzymatic hydrolysis process. Ralstonia eutropha ATCC 17699 was tested for its
      ability to synthesize poly-3-hydroxybutyrate (PHB) using PS hydrolysates as its
      sole carbon source. It is noteworthy that dry cell weight, polyhydroxyalkanoate
      (PHA) accumulation and PHB yield with the use of laboratory-grade sugars were
      similar to those achieved with PS-derived sugars. Under optimized conditions, we
      observed maximal PHA accumulation (75.45%) and PHB production (11.42 g/L) within
      48 h of fermentation. After PHB recovery, the physicochemical properties of PHB
      were determined by various analytical techniques, showed the results were
      consistent with the characteristics of a standard polymer of PHB. Thus, the PS
      hydrolysate proved to be an excellent cheap carbon substrate for PHB production.

PMID- 26206742
TI  - The significance of early post-exercise ST segment normalization.
AB  - BACKGROUND: The persistence of ST segment depression in recovery signifies a
      strongly positive exercise treadmill test (ETT). However, it is unclear if early
      recovery of ST segments portends a similar prognosis. We sought to determine if
      persistence of ST depression into recovery correlates with ischemic burden based
      on myocardial perfusion imaging (MPI). METHODS: This was a retrospective analysis
      of 853 consecutive patients referred for exercise MPI at a tertiary academic
      center over a 24-month period. Patients were stratified into three groups based
      on the results of the ETT: normal (negative ETT), persistence (positive ETT with
      >1mm ST segment depression at 1minute in recovery) and early normalization
      (positive ETT with <1mm ST segment depression at 1minute in recovery). Summed
      stress scores (SSSs) were calculated then for each patient, while the coronary
      anatomy was reported for the subset of patients who received coronary angiograms.
      RESULTS: A total of 513 patients had a negative ETT, 235 patients met criteria
      for early normalization, while 105 patients met criteria for persistence. The
      persistence group had a significantly greater SSS (8.48+/-7.77) than both the
      early normalization (4.34+/-4.98, p<0.001) and normal (4.47+/-5.31, p<0.001)
      groups. The SSSs of the early normalization and normal groups were not
      statistically different and met the prespecified non-inferiority margin (mean
      difference 0.12, -0.66=lower 95% CI, p<0.001). Among the 87 patients who
      underwent an angiogram, significant three-vessel or left main disease was seen in
      39.3% of the persistence group compared with 5.9% of normal and 7.4% of early
      normalization groups. CONCLUSION: Among patients with an electrically positive
      ETT, recovery of ST segment depression within 1minute was associated with a lower
      SSS than patients with persistence of ST depression beyond 1minute. Furthermore,
      early ST segment recovery conferred a similar SSS to patients with a negative
      ETT. These results suggest that among patients evaluated for chest pain with a
      positive ETT, early recovery of the ST segment during recovery is associated with
      a significantly less ischemic burden on subsequent MPI and thus may represent a
      false positive finding in exercise treadmill testing.

PMID- 26206743
TI  - Author's reply to Brown.

PMID- 26206744
TI  - Polytraumatism and solid organ bleeding syndrome: The role of imaging.
AB  - In multiple injuries, features of bleeding from solid organs mostly involve the
      liver, spleen and kidneys and may be treated by embolization. The indications and
      techniques for embolization vary between organs and depend on the pathophysiology
      of the injuries, type of vascularization (anastomotic or terminal) and type of
      embolization (curative or preventative). Interventional radiologists should have
      a full understanding of these indications and techniques and management
      algorithms should be produced within each facility in order to define the
      respective place of the different treatment options. 

PMID- 26206745
TI  - [Are spiculated lesions of lung parenchyma always malignant?].

PMID- 26206746
TI  - Variation in sorption of propiconazole with biochars: The effect of temperature,
      mineral, molecular structure, and nano-porosity.
AB  - Sorption behavior of propiconazole (PROPI) by plant-residue derived biochars
      (PLABs) and animal waste-derived biochars (ANIBs) obtained at three heating
      treatment temperatures (HTTs) (300, 450 and 600  degrees C) (e.g., BCs300,
      BCs450, and BCs600) and their corresponding de-ashed BCs450 was investigated.
      PLABs belonged to high- or medium-C biochars and ANIBs were low-C biochars.
      Surface C concentrations of the tested biochars were generally higher than their
      corresponding bulk C. Surface polar groups were mainly composed of O-containing
      groups of minerals within biochars. The nonlinearity coefficients (n) of
      propiconazole (PROPI) sorption isotherms ranged from 0.23 to 0.64, which was
      significantly and negatively related to organic carbon (OC)-normalized CO2
      surface area (CO2-SA/OC) of biochars. This correlation along with the positive
      relationship between CO2-SA/OC and aromaticity indicates that pore-filling in
      nanopores within aromatic C dominate nonlinear PROPI sorption. HTTs or C contents
      do not necessarily regulate PROPI sorption. Removal of minerals from BCs450
      elevated PROPI sorption because minerals may exert certain influence on sorption
      via impacting spatial arrangement of polar groups and/or organic matter (OM)
      mineral interactions. This study helps to better understand sorption behavior of
      PROPI to biochars and evaluate the potential role of biochar in water treatment
      systems.

PMID- 26206747
TI  - Copper and zinc adsorption by softwood and hardwood biochars under elevated
      sulphate-induced salinity and acidic pH conditions.
AB  - Biochar adsorption may lower concentrations of soluble metals in pore water of
      sulphidic Cu/Pb-Zn mine tailings. Unlike soil, high levels of salinity and
      soluble cations are present in tailing pore water, which may affect biochar
      adsorption of metals from solution. In the present study, removal of soluble
      copper (Cu) and zinc (Zn) ions by soft- (pine) and hard-wood (jarrah) biochars
      pyrolysed at high temperature (about 700  degrees C) was evaluated under typical
      ranges of pH and salinity conditions resembling those in pore water of sulphidic
      tailings, prior to their direct application into the tailings. Surface
      alkalinity, cation exchange capacity, and negative surface charge of biochars
      affected Cu and Zn adsorption capacities. Quantitative comparisons were provided
      by fitting the adsorption equilibrium data with either the homogeneous or
      heterogeneous surface adsorption models (i.e. Langmuir and Freundlich,
      respectively). Accordingly, the jarrah biochar showed higher Cu and Zn adsorption
      capacity (Qmax=4.39 and 2.31 mg/g, respectively) than the softwood pine biochar
      (Qmax=1.47 and 1.00 mg/g). Copper and Zn adsorption by the biochars was favoured
      by high pH conditions under which they carried more negative charges and Cu and
      Zn ions were predicted undergoing hydrolysis and polymerization. Within the
      tested range, salinity had relatively weak effects on the adsorption, which
      perhaps influenced the surface charge and induced competition for negative
      charged sites between Na(+) and exchangeable Ca(2+) and/or heavy metal ions.
      Large amounts of waste wood/timber at many mine sites present a cost-effective
      opportunity to produce biochars for remediation of sulphidic tailings and seepage
      water.

PMID- 26206748
TI  - High expression and biosilica encapsulation of alkaline-active carbonic anhydrase
      for CO2 sequestration system development.
AB  - Carbonic anhydrase (CA) is a biocatalyst for CO2 sequestration because of its
      distinctive ability to accelerate CO2 hydration. High production and efficient
      immobilization of alkaline-active CAs are required, because one potential
      application of CA is its use in the alkaline solvent-based CO2
      absorption/desorption process. Here, we designed and applied an alpha-type CA
      from Hahella chejuensis (HCA), which was reported as highly active in alkaline
      conditions, but was mostly expressed as insoluble forms. We found that the signal
      peptide-removed form of HCA [HCA(SP-)] was successfully expressed in the soluble
      form [~70mg of purified HCA(SP-) per L of culture]. HCA(SP-) also displayed high
      pH stability in alkaline conditions, with maximal activity at pH 10; at this pH,
      ~90% activity was maintained for 2h. Then, we prepared HCA(SP-)-encapsulated
      silica particles [HCA(SP-)@silica] via a spermine-mediated bio-inspired
      silicification method. HCA(SP-)@silica exhibited high-loading and highly stable
      CA activity. In addition, HCA(SP-)@silica retained more than 90% of the CA
      activity even after 10 cycles of use in mild conditions, and ~80% in pH 10
      conditions. These results will be useful for the development of practical CO2
      sequestration processes employing CA. 

PMID- 26206749
TI  - Development of Port-Site Metastases Following Thoracoscopic Resection of a
      Neuroblastoma.
AB  - We report a 26-month-old female who developed port-site metastases of a
      neuroblastoma following minimally invasive thoracoscopic interventions. After
      diagnosis of an intrathoracic low-risk neuroblastoma and 6 months of observation,
      she developed respiratory problems. She subsequently underwent total resection of
      a locally progressive tumor via thoracoscopy. Six months later, she developed
      local relapse and subcutaneous metastases within the thoracic wall. These port
      site metastases were most likely iatrogenic. After excision of metastases, the
      residual tumor responded well to salvage chemotherapy. The patient has remained
      in remission for over 4 years.

PMID- 26206750
TI  - Is there something fishy about the regulation of the ryanodine receptor in the
      fish heart?
AB  - NEW FINDINGS: What is the topic of this review? Excitation-contraction coupling
      in fish hearts is maintained over a range of temperatures that would be
      cardioplegic to most mammals. Here, we review what is known about the fish
      cardiac ryanodine receptor, and consider how it may be regulated in a different
      manner from the mammalian cardiac isoforms of this channel. What advances does it
      highlight? We highlight how a better understanding of the basic gating and
      conducting properties of fish cardiac ryanodine receptors could provide
      considerable insight into mechanisms underlying sarcoplasmic reticulum calcium
      release in fish hearts and the role of the sarcoplasmic reticulum in the
      evolution of the heart. The fish cardiac sarcoplasmic reticulum (SR) holds large
      quantities of Ca(2+), but calcium-induced calcium release (CICR) is weak in these
      myocytes, and contraction and relaxation are largely determined by
      transsarcolemmal Ca(2+) flux. Many fish species live in a cold and seasonally
      variable thermal habitat, which could provide challenges to regulation of
      excitation-contraction coupling. Here, we focus on the cardiac SR Ca(2+)-release
      channel (RyR2) in fish and ask whether it may be regulated in a different manner
      from the mammalian RyR2. We review data indicating that fish cardiac RyR are
      present at lower density, are more spatially separated within the SR membrane and
      are less responsive to cytosolic Ca(2+) than mammalian RyR2 channels. All of
      these features would contribute to the weak CICR evident from functional studies.
      We also consider how CICR can be enhanced in fish myocytes following beta
      adrenergic stimulation and application of low levels of caffeine, and how acute
      and chronic temperature change may affect the gating properties of fish RyR2s. It
      is clear that a lack of insight into the fundamental gating and conductance
      properties of fish RyR2 channels is hindering our understanding of the role of
      the SR in fish cardiac excitation-contraction coupling. We conclude by reflecting
      on how studies that probe the biophysical properties of fish RyR2 channel gating
      in response to various ligands and temperatures would be very instructive for our
      understanding of the role of the SR in the evolution of the heart.

PMID- 26206751
TI  - TITF1 and TITF2 loci variants indicate significant associations with thyroid
      cancer.
AB  - A number of studies have investigated the influence of TITF1 and TITF2 genetic
      variants on thyroid carcinogenesis, but their associations remain unclear due to
      the controversial results. The objective of this study was to test the hypothesis
      that TITF1 and TITF2 variants modulate thyroid cancer susceptibility. Eligible
      studies were identified through online searches supplemented by manual search.
      Either the DerSimonian and Laird method or the Mantel-Haenszel method was used to
      estimate the risk of thyroid cancer (ORs and 95 % CIs). The pooled ORs were
      calculated assuming the allele model. We identified a total of 10 publications
      concerning the topic of interest. Overall, meta-analysis of rs944289 showed 1.11
      fold increased risk of thyroid cancer related to the risk T allele (T vs. C: OR
      1.11, 95 % CI 1.05-1.17). For rs965513, individuals carrying the risk A allele,
      compared to individuals with the G allele, had 31 % higher risk of thyroid cancer
      (A vs. G: OR 1.31, 95 % CI 1.17-1.46). Analyses in total samples for rs1867277,
      rs1443434, and rs907580 yielded similar associations (A vs. G: OR 1.22, 95 % CI
      1.06-1.39; G vs. T: OR 1.26, 95 % CI 1.09-1.45; T vs. C: OR 1.42, 95 % CI 1.21
      1.66, respectively). The significant association persisted among Caucasians in
      subgroup analyses for rs944289 and rs965513. The genetic susceptibility of
      thyroid cancer seems likely to be associated with the risk allele at rs944289 in
      the TITF1 gene and at rs1867277, rs965513, rs1443434, and rs907580 in the TITF2
      gene.

PMID- 26206752
TI  - Hypothalamo-pituitary adrenal axis and sympatho-adrenal medullary system
      responses to psychological stress were not attenuated in women with elevated
      physical fitness levels.
AB  - It is not clear if higher levels of cardiorespiratory fitness are associated with
      lower hypothalamo-pituitary adrenal (HPA) axis and sympatho-adrenal medullary
      (SAM) system reactivity to psychological stress in women. The association between
      cardio-metabolic risk markers and acute physiological responses to psychological
      stress in women who differ in their cardiorespiratory fitness status has also not
      been investigated. Women with high (n = 22) and low (n = 22) levels of fitness
      aged 30-50 years (in the mid-follicular phase of the menstrual cycle) were
      subjected to a Trier Social Stress Test (TSST) at 1500 h. Plasma concentrations
      of cortisol, adrenaline (Adr), noradrenaline (NA), and dopamine (DA) were
      measured in samples collected every 7-15 min from 1400 to 1700 h. Heart rate and
      blood pressure were measured at the same time points. Low-fit women had elevated
      serum triglyceride, cholesterol/HDL ratio, fasting glucose, and HOMA-IR levels
      compared with high-fit women. While cortisol, Adr, NA, HR, and blood pressure all
      demonstrated a significant response to the TSST, the responses of these variables
      did not differ significantly between high- and low-fit women in response to the
      TSST. Dopamine reactivity was significantly higher in the low-fit women compared
      with high-fit women. There was also a significant negative correlation between
      VO2 max and DA reactivity. These findings suggest that, for low-fit women aged 30
      50 years, the response of HPA axis and SAM system to a potent acute psychological
      stressor is not compromised compared to that in high-fit women.

PMID- 26206753
TI  - PET imaging in ectopic Cushing syndrome: a systematic review.
AB  - Cushing syndrome due to endogenous hypercortisolism may cause significant
      morbidity and mortality. The source of excess cortisol may be adrenal, pituitary,
      or ectopic. Ectopic Cushing syndrome is sometimes difficult to localize on
      conventional imaging like CT and MRI. After performing a multilevel
      thoracoabdominal imaging with CT, the evidence regarding the use of radiotracers
      for PET imaging is unclear due to significant molecular and etiological
      heterogeneity of potential causes of ectopic Cushing's syndrome. In our
      systematic review of literature, it appears that GalLium-based (Ga68)
      somatostatin receptor analogs have better sensitivity in diagnosis of bronchial
      carcinoids causing Cushing syndrome and FDG PET appears superior for small-cell
      lung cancers and other aggressive tumors. Further large-scale studies are needed
      to identify the best PET tracer for this condition. 

PMID- 26206754
TI  - Preexisting adrenal masses in patients with adrenocortical carcinoma: clinical
      and radiological factors contributing to delayed diagnosis.
AB  - Adrenocortical carcinoma (ACC) is a rare endocrine malignancy that is usually
      large (>5 cm) at time of diagnosis. Delayed diagnosis significantly worsens
      survival. We describe adrenal gland morphology prior to ACC diagnosis and discern
      potential causes of delayed diagnosis. ACC patients seen at The University of
      Texas MD Anderson Cancer Center between 1998 and 2014 who had cross-sectional
      body imaging >=3 months prior to their diagnosis. We conducted a detailed review
      of clinical and radiological features in these patients prior to ACC diagnosis.
      Of 439 patients with ACC, 25 had imaging preceding ACC diagnosis (5 with normal
      adrenal glands and 20 with preexisting masses). On the first available images,
      the median mass size was 2.8 cm (range 0-9) with median precontrast density of 36
      Hounsfield units (range 17-43) and became 9 cm (range 1-18) at the time of ACC
      diagnosis. The median interval between first available image and ACC diagnosis
      was 20 months (range 3-89). In the 5 patients whose initial images showed normal
      adrenal glands, the time between the last normal scan and ACC diagnosis ranged
      from 5 to 36 months. The most common reason for delayed ACC diagnosis was the
      presumed benign status of the preexisting mass (n = 13, 65 %). Radiologically
      suspicious adrenal masses can precede ACC diagnosis and have variable growth
      patterns. ACC can also develop de novo within a few months in a radiologically
      documented normal adrenal gland. The presumed benignancy of preexisting masses
      based on size is the main reason for delayed ACC diagnosis.

PMID- 26206755
TI  - RE-IIBP Methylates H3K79 and Induces MEIS1-mediated Apoptosis via H2BK120
      Ubiquitination by RNF20.
AB  - Histone lysine methylation contributes to transcriptional regulation by serving
      as a platform for the recruitment of various cofactors. Intense studies have been
      conducted for elucidating the functional meaning of H3K79 methylation, and to
      date, the only known HMTase responsible for the modification was DOT1L. In this
      study, we report that the MMSET isoform RE-IIBP has HMTase activity for H3K79. It
      was uncovered that RE-IIBP up-regulates MEIS1 transcription through H3K79
      methylation via recruitment to the MEIS1 promoter. By means of proteomic and
      biochemical analysis, association of RE-IIBP with the E3 ubiquitin ligase RNF20
      was demonstrated for synergistic activation of MEIS1 transcription via H3K79
      HMTase activity. Furthermore, It was observed that RE-IIBP induces MEIS1-mediated
      apoptosis, which was dependent on H2BK120 ubiquitination by RNF20. These findings
      suggest RE-IIBP as another candidate for further studies to elucidate the
      mechanism of H3K79 methylation and its biological functions. 

PMID- 26206756
TI  - Mapping Consistent Rice (Oryza sativa L.) Yield QTLs under Drought Stress in
      Target Rainfed Environments.
AB  - BACKGROUND: Drought stress is a major limitation to rainfed rice production and
      yield stability. Identifying yield-associated quantitative trait loci (QTLs) that
      are consistent under drought stress predominant in target production
      environments, as well as across different genetic backgrounds, will help to
      develop high-yielding rice cultivars suitable for water-limited environments
      through marker-assisted breeding (MAB). Considerable progress has been made in
      mapping QTLs for drought resistance traits in rice; however, few have been
      successfully used in MAB. RESULTS: Recombinant inbred lines of IR20 *
      Nootripathu, two indica cultivars adapted to rainfed target populations of
      environments (TPEs), were evaluated in one and two seasons under managed stress
      and in a rainfed target drought stress environment, respectively. In the managed
      stress environment, the severity of the stress meant that measurements could be
      made only on secondary traits and biomass. In the target environment, the lines
      experienced varying timings, durations, and intensities of drought stress. The
      rice recombinant inbred lines exhibited significant genotypic variation for
      physio-morphological, phenological, and plant production traits under drought.
      Nine and 24 QTLs for physio-morphological and plant production traits were
      identified in managed and natural drought stress conditions in the TPEs,
      respectively. Yield QTLs that were consistent in the target environment over
      seasons were identified on chromosomes 1, 4, and 6, which could stabilize the
      productivity in high-yielding rice lines in a water-limited rainfed ecosystem.
      These yield QTLs also govern highly heritable key secondary traits, such as leaf
      drying, canopy temperature, panicle harvest index and harvest index. CONCLUSION:
      Three QTL regions on chromosome 1 (RM8085), chromosome 4 (I12S), and chromosome 6
      (RM6836) harbor significant additive QTLs for various physiological and yield
      traits under drought stress. The similar chromosomal region on 4 and 6 were found
      to harbor QTLs for canopy temperature and leaf drying under drought stress
      conditions. Thus, the identified large effect yield QTLs could be introgressed to
      develop rice lines with stable yields under varying natural drought stress
      predominant in TPEs.

PMID- 26206757
TI  - Coexpression Network Analysis of Macronutrient Deficiency Response Genes in Rice.
AB  - BACKGROUND: Macronutrients are pivotal elements for proper plant growth and
      development. Although extensive gene expression profiling revealed a large number
      of genes differentially expressed under various nutrient deprivation,
      characterization of these genes has never been fully explored especially in rice.
      Coexpression network analysis is a useful tool to elucidate the functional
      relationships of genes based on common expression. Therefore, we performed
      microarray analysis of rice shoot under nitrogen (N), phosphorus (P), and
      potassium (K) deficiency conditions. Moreover, we conducted a large scale
      coexpression analysis by integrating the data with previously generated gene
      expression profiles of organs and tissues at different developmental stages to
      obtain a global view of gene networks associated with plant response to nutrient
      deficiency. RESULTS: We statistically identified 5400 differentially expressed
      genes under the nutrient deficiency treatments. Subsequent coexpression analysis
      resulted in the extraction of 6 modules (groups of highly interconnected genes)
      with distinct gene expression signatures. Three of these modules comprise mostly
      of downregulated genes under N deficiency associated with distinct functions such
      as development of immature organs, protein biosynthesis and photosynthesis in
      chloroplast of green tissues, and fundamental cellular processes in all organs
      and tissues. Furthermore, we identified one module containing upregulated genes
      under N and K deficiency conditions, and a number of genes encoding protein
      kinase, kinase-like domain containing protein and nutrient transporters. This
      module might be particularly involved in adaptation to nutrient deficiency via
      phosphorylation-mediated signal transduction and/or post-transcriptional
      regulation. CONCLUSIONS: Our study demonstrated that large scale coexpression
      analysis is an efficient approach in characterizing the nutrient response genes
      based on biological functions and could provide new insights in understanding
      plant response to nutrient deficiency.

PMID- 26206758
TI  - Surgical efficacy of minimally invasive thoracic discectomy.
AB  - We aimed to determine the clinical indications and surgical outcomes for
      thoracoscopic discectomy. Thoracic disc disease is a rare degenerative process.
      Thoracoscopic approaches serve to minimize tissue injury during the approach, but
      critics argue that this comes at the cost of surgical efficacy. Current reports
      in the literature are limited to small institutional patient series. We
      systematically identified all English language articles on thoracoscopic
      discectomy with at least two patients, published from 1994 to 2013 on MEDLINE,
      Science Direct, and Google Scholar. We analyzed 12 articles that met the
      inclusion criteria, five prospective and seven retrospective studies comprising
      545 surgical patients. The overall complication rate was 24% (n=129), with
      reported complications ranging from intercostal neuralgia (6.1%), atelectasis
      (2.8%), and pleural effusion (2.6%), to more severe complications such as
      pneumonia (0.8%), pneumothorax (1.3%), and venous thrombosis (0.2%). The average
      reported postoperative follow-up was 20.5 months. Complete resolution of symptoms
      was reported in 79% of patients, improvement with residual symptoms in 10.2%, no
      change in 9.6%, and worsening in 1.2%. The minimally invasive endoscopic
      approaches to the thoracic spine among selected patients demonstrate excellent
      clinical efficacy and acceptable complication rates, comparable to the open
      approaches. Disc herniations confined to a single level, with small or no
      calcifications, are ideal for such an approach, whereas patients with calcified
      discs adherent to the dura would benefit from an open approach.

PMID- 26206759
TI  - High serum phosphate concentration as the result of smoking might underlie the
      lower risk of Parkinson's disease.
AB  - Epidemiological studies have found a negative association between cigarette
      smoking and Parkinson's disease (PD): PD patients are approximately 50% less
      likely to have smoked cigarettes than age- and sex-matched controls. In both
      women and men, the PD protection effect of smoking may be explained by higher
      levels of phosphate in serum (S-P) and triglycerides (S-TG) in smokers compared
      to non-smokers. That is, the protecting effect from smoking could be mediated by
      either a high S-P or high S-TG levels. I suggest that higher S-P as the result of
      smoking may be associated with intracellular depletion of Pi in skeletal muscle
      and that this depletion of Pi is associated with increased availability of
      phosphate for the brain. This increased phosphate availability would protect
      against PD, as oxidative phosphorylation in the mitochondria is a central and
      persistent phenomenon in the pathogenesis cascade of PD. Phosphate is necessary
      for energy production in the form of creatine phosphate (CP) and adenosine-tri
      phosphate (ATP) in the brain and skeletal muscle. As such, hypophosphatemia
      increases risk of cell death. In some clinical instances, this energy depletion
      may pre-dispose to dopamine neuron death. Mitochondrial dysfunction is associated
      with the generation of oxidative stress and mediates the induction of apoptosis.
      Studies with NMR spectroscopy reveal that an energy deficit in brain cells is a
      strong mark for PD although this differed for men and women. Compared to women,
      men had lower serum phosphate and ATP levels in the brain (about 15% lower). In
      addition to sex differences, age, stress, and malnutrition may cause low serum
      phosphate levels, a situation that could contribute to the lack of energy
      available to the brain and the risk of PD. As hypophosphatemia is present in
      overnutrition and has an inverse relation with a high BMI, both obesity and
      malnutrition are considered to be presumptive risk factor for PD. 

PMID- 26206760
TI  - Hypnosis and music interventions (HMIs) inactivate HIF-1: A potential curative
      efficacy for cancers and hypertension.
AB  - Hypnosis and music interventions (HMIs) have shown positive influence on cancers
      for nearly 200years, but the underlying mechanisms were rarely explored
      systematically. The hypothesis suggests a potential curative efficacy of HMIs on
      cancers by inhibiting hypoxia inducible factor-1 (HIF-1), which is a key mediator
      of cancer development, especially under hypoxic conditions. HMIs are sufficient
      to attenuate the pain and anxiety degree of individuals, improve multiple
      psychological and physiological parameters, and consequently, lead to increased
      oxygen saturation in vivo. Furthermore, abundant oxygen in vivo inhibits the
      activation of HIF-1 and potentially blockades kinds of HIF-1-induced oncogenic
      signaling pathways. The hypothesized efficacy of HMIs is very similar to anti
      cancer medicines targeting HIF-1. The implication of the hypothesis in preventing
      hypertension is also discussed. In summary, the hypothesis clearly suggests the
      potential involvement of the convenient, safe, non-pharmaceutical, and low-cost
      HMIs in preventing HIF-1-mediated diseases, including cancers and hypertension. 

PMID- 26206761
TI  - Endogamy and suicide: An observation-based hypothesis.
AB  - Suicide is a complex and multifactorial behavior, which is likely the result of
      distinct pathways in different individuals or groups. Endogamy has been
      associated with numerous diseases, including behavioral disorders. Here, we
      discuss the hypothesis of endogamy as one mechanism facilitating high rates of
      suicide in some small and isolated groups of people across the world. To support
      our hypothesis, we describe four geographically and culturally distinct
      populations (the Aguarunas of Peru, the Vaqueiros of Spain, the Baruyas of New
      Guinea, and the Palawans of the Philippines), which present the following
      characteristics: (1) a high level of isolation and endogamy; (2) very high rates
      of suicide restricted to one group with (3) adjacent groups of similar origin and
      culture displaying low rates of suicide. Within these four distinct populations,
      endogamy could act in one isolated group as the amplifier of both selected
      genetic risk alleles and microcultural values (e.g. suicide as an acceptable
      solution), beyond cultural and genetic traits shared by the whole population (and
      therefore found in all groups). Genetic and microcultural risk factors are
      transmitted through close kinship and imitation/modeling, and could interact to
      increase the frequency of vulnerable individuals leading, in turn, to heightened
      rates of suicide. Culture could sometimes additionally act by generating
      stressful conditions for some individuals (e.g. lower social status and
      maltreatment). In contrast to endogamy, suicide motives (notably interpersonal
      conflicts) and mental disorders appear to be universal risk factors. More
      investigation of this endogamy hypothesis is necessary, which could represent a
      singular case of gene-culture co-transmission and shed light on particular
      conditions of suicide genesis. 

PMID- 26206762
TI  - Is palatal vault height a determinant for nasopharyngeal carcinoma: A hypothesis?
AB  - Although environmental and genetic factors are known for nasopharyngeal
      carcinoma, the present study is an attempt to provide a hypothesis behind the
      development of NPC with regards to the anatomical factor, the hypothesis being
      that patients with a deeper palatal vault tend to have a higher risk of
      developing nasopharyngeal cancers. The objective of this study was to find out
      the palatal vault height in patients with nasopharyngeal carcinoma and compare it
      with the palatal vault height in patients with oral carcinomas. The heights of
      the palatal vault of 20 consecutive patients with nasopharyngeal carcinoma and 20
      patients with carcinoma of the oral cavity (except hard palate) as control were
      recorded. In addition, in patients with carcinoma of the nasopharynx the height
      of the palate on the CT scans was measured and correlation between these
      recordings were calculated. The palatal heights of the nasopharyngeal and oral
      cancer cohorts were compared using independent sample T test. A strong
      correlation was observed in the nasopharyngeal cancer cohort between the palatal
      height measured manually and the radiologically measured height on the CT scans
      (Pearson Correlation Coefficient - 0.633; p=0.003). The difference in the mean
      heights of the nasopharyngeal and oral cancer cohorts was statistically
      significant (p<0.001). Nasopharyngeal cancer patients tend to have a higher
      palatal vault height compared to those with carcinoma of oral cavity other than
      hard palate. In such palates with a deep vault, there is increased turbulent air
      flow leading to increased deposition of air-borne virus/carcinogens. Lingering of
      these agents may ultimately cause carcinoma of the nasopharynx. 

PMID- 26206763
TI  - Significance of the decreased risk of dialysis-related amyloidosis now proven by
      results from Japanese nationwide surveys in 1998 and 2010.
AB  - BACKGROUND: Although dialysis technology greatly improved in recent years, it
      remained unclear whether those improvements helped decrease the incidence of
      dialysis-related amyloidosis (DRA). Accordingly, we retrospectively compared the
      incidence of first-time carpal tunnel surgery (CTS)-as proxy for DRA onset-in two
      cohorts of chronic hemodialysis patients, with the second cohort studied after
      dialysis methods (especially dialyzate quality control) had greatly improved.
      METHODS: We used the 1998 and 2010 Japan Renal Data Registries to compare crude
      risk of first-time CTS the following year. After adjusting for patient background
      and laboratory data, odds ratios (ORs) for CTS in the whole cohorts and the
      populations matched by propensity score (PS) for hemodialysis and
      hemodiafiltration were calculated at a 95% confidence interval. RESULTS: Of note,
      2 02 726 patients were analyzed. In the 1998 cohort, 1.77% experienced first-time
      CTS compared with 1.30% of the 2010 cohort (P < 0.001); with 2010 as referent,
      the adjusted 1998 OR was 2.22 (1.68-2.95). Both crude risks and adjusted ORs were
      analyzed by dialysis vintage, age, pre-dialysis beta2-microglobulin (beta2m) and
      beta2m clearance, risk of CTS trending 1.5-2.0 higher in 1998 than 2010. The
      reduction was most prominent in patients with longer dialysis vintage, patients
      who were younger, and those with lower pre-dialysis beta2m levels. Similar
      results were obtained by PS-matched analysis. We also found that beta2m clearance
      >80% may reduce risk of CTS. CONCLUSIONS: The incidence of first-time CTS as
      proxy for DRA decreased significantly from 1998 to 2010. Several factors may have
      contributed to this decrease, including improved dialysis methods.

PMID- 26206764
TI  - Can decision support systems work for acute kidney injury?

PMID- 26206765
TI  - The region-of-interest size impacts on Ki67 quantification by computer-assisted
      image analysis in breast cancer.
AB  - Therapeutic decision-making in breast cancer depends on histopathologic
      biomarkers and is influenced by the Ki67 proliferation index. Computer-assisted
      image analysis (CAIA) promises to improve Ki67 quantification. Several commercial
      applications have been developed for semiautomated CAIA-based Ki67
      quantification, many of which rely on measurements in user-defined regions of
      interest (ROIs). Because of intratumoral proliferative heterogeneity, definition
      of the ROI is an important step in the analytical procedure. This study explores
      the ROI size impacts on Ki67 quantification. Whole-slide sections of 100 breast
      cancers were immunostained with the anti-Ki67 antibody 30-9 and were analyzed on
      the iScan Coreo digital pathology platform using a Food and Drug Administration
      cleared Ki67 quantification software version v5.3 (Virtuoso; Ventana, Tucson,
      TX). For each case, the Ki67 labeling index (LI) was determined in multiple ROIs
      of gradually increasing size centered around a high-proliferation area. The
      spatial Ki67 decline was modeled with nonlinear regression. Depending on the ROI
      size, the median Ki67 LI varied between 55% and 15%. The proportion of tumors
      classified as Ki67 low according to the St Gallen 2013/2015 cutoff increased from
      2% to 56%, as the ROI size increased from 50 to 10,000 cells captured. The
      interrater reliability of conventional Ki67 assessment versus CAIA-based Ki67
      quantification was also dependent on the ROI size and varied between slight and
      almost perfect agreement (Cohen kappa = 0.06-0.85). In conclusion, the ROI size
      is a critically important parameter for semiautomated Ki67 quantification by
      CAIA. Ki67 LIs determined on platforms like iScan Coreo/Virtuoso require an ROI
      size adjustment, for which we offer a downloadable data transformation tool.

PMID- 26206766
TI  - The Feasibility and Efficiency of Volumetric Modulated Arc Therapy-Based Breath
      Control Stereotactic Body Radiotherapy for Liver Tumors.
AB  - There are strong evidences showing the promising oncologic results of
      stereotactic body radiotherapy for liver tumors. This study aims to investigate
      the feasibility, plan quality, and delivery efficiency of image-guided volumetric
      modulated arc therapy-based voluntary deep exhale breath-holding technique in the
      stereotactic body radiotherapy for liver tumors. Treatment was planned using
      volumetric modulated arc therapy with 2 modified partial arc and replanned using
      intensity modulated radiation therapy technique for comparison. Dosimetric
      parameters were calculated for plan quality assessment. Quality assurance studies
      included both point and multiple planar dose verifications. Daily cone beam
      computed tomography imaging was used to measure and correct positional errors for
      target volumes and critical structures immediately prior to and during treatment
      delivery. Total monitor units and delivery times were also evaluated. No
      significant dosimetric difference was found between volumetric-modulated arc
      therapy and conventional intensity modulated radiation therapy plans. Both
      techniques were able to minimize doses to organs at risk including normal liver,
      kidneys, spinal cord, and stomach. However, the average monitor units with
      volumetric-modulated arc therapy were significantly lower (29.2%) than those with
      intensity modulated radiation therapy (P = .012). The average beam-on time in
      volumetric-modulated arc therapy plans was 22.2% shorter than that in intensity
      modulated radiation therapy plans. In conclusion, it is feasible to utilize
      volumetric modulated arc therapy in the treatment planning of stereotactic body
      radiotherapy for liver tumors under breath control mode. In comparison to
      conventional intensity modulated radiation therapy plans, volumetric modulated
      arc therapy plans are of high efficiency with less monitor units, shorter beam-on
      time, tolerable intrafractional errors as well as better dosimetrics, meriting
      further investigations, and clinical evaluations.

PMID- 26206767
TI  - A Feasibility Study on Ribs as Anatomical Landmarks for Motion Tracking of Lung
      and Liver Tumors at External Beam Radiotherapy.
AB  - At external beam radiotherapy for some tumors located at thorax region due to
      lack of information in gray scale fluoroscopic images tumor position
      determination is problematic. One of the clinical strategies is to implant clip
      as internal fiducial marker inside or near tumor to represent tumor position
      while the contrast of implanted clip is highly observable rather than tumor. As
      alternative, using natural anatomical landmarks located at thorax region of
      patient body is proposed to extract tumor position information without implanting
      clips that is invasive method with possible side effect. Among natural landmarks,
      ribs of rib-cage structure that result proper visualization at X-ray images may
      be optimal as representative for tumor motion. In this study, we investigated the
      existence of possible correlation between ribs as natural anatomical landmarks
      and various lung and liver tumors located at different sites as challenging
      issue. A simulation study was performed using data extracted from 4-dimensional
      extended cardiac-torso anthropomorphic phantom that is able to simulate motion
      effect of dynamic organs, as well. Several tumor sites with predefined distances
      originated from chosen ribs at anterior-posterior direction were simulated at 3
      upper, middle, and lower parts of chest. Correlation coefficient between ribs and
      tumors was calculated to investigate the robustness of ribs as anatomical
      landmarks for tumor motion tracking. Moreover, a consistent correlation model was
      taken into account to track tumor motion with a rib as best candidate among
      selected ribs. Final results represent availability of using rib cage as
      anatomical landmark to track lung and liver tumors in a noninvasive way.
      Observations of our calculations showed a proper correlation between tumors and
      ribs while the degree of this correlation is changing depends on tumor site while
      lung tumors are more varied and complex with less correlation with ribs motion
      against liver tumors.

PMID- 26206768
TI  - A Single-Site Retrospective, Nonrandomized Study of Accelerated Partial Breast
      Irradiation Brachytherapy for Early-Stage Breast Cancer Treatment to Evaluate
      Local Tumor Control, Cosmetic Outcome, and Toxicities.
AB  - PURPOSE: To evaluate the efficacy and safety of the accelerated partial breast
      irradiation brachytherapy with a combination of applicators at a community
      hospital cancer center. METHODS AND MATERIALS: Between 2005 and 2009, 120
      patients with early-stage breast cancer were being followed after treatment with
      accelerated partial breast irradiation brachytherapy using MammoSite, single or
      multilumen balloon, or Contura multilumen balloon. After their lumpectomy
      surgery, each patient was treated with Ir-192 high-dose rate unit following
      radiation therapy oncology group 0413 guidelines. The patients had multiple
      follow-ups at 6 months, 1 year, 2 years, 3 years, or more. RESULTS: Based on the
      Harvard Breast Cosmesis Scale, 95.00% of patients described their cosmetic
      evaluation as the treated breast essentially the same as the opposite side
      (excellent) or minimal but identifiable effects were noticed from radiation
      (good). After a median follow-up of 36 months, the local recurrence rate was
      1.66% and a disease-free survival is 98.3%. Forty-two patients reported 85
      adverse events, which were fibrosis: 24.70%, hyperpigmentation: 20.00%, radiation
      skin reaction: 7.05%, seroma: 7.05%, breast pain: 7.05%, erythema: 5.88%, and
      other events were less than 5.00%. Of all the adverse events recorded, grade 1 to
      3 events are 95.29% (n = 81), 2.35% (n = 2), and 2.35% (n = 2). There was no
      grade 4 or 5 events recorded. CONCLUSIONS: Our study has shown promising results
      for delivering radiation with MammoSite, single or multilumen balloon, or Contura
      multilumen balloon and has been successful in achieving local control in patients
      with early-stage breast cancer.

PMID- 26206769
TI  - Percutaneous Tumor Ablation: Cryoablation Facilitates Targeting of Free
      Epirubicin-Ethanol-Ioversol Solution Interstitially Coinjected in a Rabbit VX2
      Tumor Model.
AB  - This acute study was aimed at exploring the ability of a cryoablative lesion to
      drive the distribution of a concomitant in situ injection of a free epirubicin
      ethanol-ethiodol-methylene blue mixture. We report the feasibility and safety of
      this new percutaneous computed tomography-guided combinatorial ablative procedure
      on VX2 tumors. Eight New Zealand white rabbits bearing 16 tumors on both side of
      the back muscle were randomly selected and treated on the same day with the
      following procedures: (1) 8 concomitant cryoablation and interstitial
      chemotherapy and (2) 8 intratumor marginal chemotherapy. For the latter, an
      injection needle was positioned at the inner distal margin of a first selected
      tumor side, where the chemotherapy was delivered during 5 serial sequences. For
      the concomitant therapy, a single cryoneedle maintained the ice front at the
      tumor margin, where a needle delivered the drug dose during 5 freeze-injection
      thaw sequences. Enhanced computed tomography scans on days 3, 7, and 10 assessed
      the tumor contours and the tracer localization. Two rabbits were killed on days
      0, 3, 7, and 10 for gross and histopathological analyses. During the concomitant
      therapy, ioversol was distributed at the tumor and iceball margins along with the
      methylene blue. Enhanced computed tomography on days 3, 7, and 10 showed a focal
      enlarging defect of the tumor marginal enhancing rim. The rim coincided with
      focal necrosis at histopathology. During the intratumor chemotherapy procedure,
      computed tomography showed that the tracers distributed mostly over the tumor
      mass. No marginal necrosis was detected at histopathology. On day 10, the tumor
      size for the intratumor chemotherapy group was twice that of the concomitant
      therapy group. No adverse events were observed. In this VX2 tumor model, our
      image-guided concomitant therapy is feasible and may enhance the effectiveness of
      a free epirubicin tracer mixture at the tumor margin.

PMID- 26206770
TI  - [Immunomonitoring for cytomegalovirus infection in kidney transplantation:
      Development and prospects].
AB  - Cytomegalovirus infection in kidney transplantation is associated with increased
      morbidity and mortality through direct and indirect effects. International
      guidelines had been recently updated, focusing on diagnostic, prevention
      strategies and curative treatment. Cytomegalovirus-specific immune response plays
      also an important function in controlling the virus. Here, we propose to present
      the different components of this specific immune response and the advantages of
      immune monitoring for patient's management: identification of patients who
      require a treatment, adaptation of curative treatment length, guidance for
      resistance genotypic testing. 

PMID- 26206771
TI  - [Outcome of rapidly progressive glomerulonephritis post-streptococcal disease in
      children].
AB  - BACKGROUND: Rapidly progressive glomerulonephritis is a rare form of
      postinfectious glomerulonephritis. The aim of this study was to describe the
      outcome of our patients with severe post-streptococcal glomerulonephritis.
      METHODS: This retrospective study was conducted in the department of pediatrics
      in Charles-Nicolle Hospital during a period of 13 years (1997-2009). RESULTS:
      Twenty-seven children were identified. The mean age was 8.7 years. All patients
      presented renal failure at presentation. The mean serum creatinine at
      presentation was 376.9 MUmol/L. Six patients presented nephrotic syndrome. Twenty
      six children had renal biopsies. Renal biopsies showed crescents in 24 cases.
      Eighteen children received pulse dose of corticosteroids (66.6%) and 6 children
      (22%) received pulse dose of corticosteroids and cyclophosphamide. Eleven
      patients required dialysis. At last follow-up, 22 patients (81.5%) had normal
      kidney function, 2 had renal dysfunction and 3 reached end stage renal disease.
      The only significant determinant for renal survival was the supportive dialysis
      (P=0.015). CONCLUSION: Rapidly progressive glomerulonephritis is uncommon. There
      have been significant advancements in supportive, as well as specific therapy,
      but the outcome continues to be poor.

PMID- 26206772
TI  - [Early human transplants: 60th anniversary of the first successful kidney
      transplants].
AB  - First kidney transplant attempts begin with the 20th century: improving vascular
      sutures, understanding the phenomena of rejection or tolerance, then progress in
      HLA groups enable early success in the second half of the century. Definition of
      brain death, use of corticosteroids, radiotherapy and prime immunosuppressors
      promote the development of transplants. Discover of cyclosporine in the 1980s,
      and legislative developments augur a new era. Many advances are arising: use of
      stem cells from the donor, enhancement of Maastricht 3 donor or living donation.
      Finally organ transplantation remains an immense human adventure, but also
      scientific and ethic. 

PMID- 26206773
TI  - The CD40/CD40L axis in glioma progression and therapy.

PMID- 26206774
TI  - The effects of anti-angiogenic therapy on the formation of radiation-induced
      microbleeds in normal brain tissue of patients with glioma.
AB  - BACKGROUND: Radiotherapy (RT) is an integral component in managing patients with
      glioma, but the damage it may cause to healthy brain tissue and quality of life
      is of concern. Susceptibility-weighted imaging (SWI) is highly sensitive to the
      detection of microbleeds that occur years after RT. This study's goals were to
      characterize the evolution of radiation-induced microbleeds in normal-appearing
      brain and determine whether the administration of an anti-angiogenic agent
      altered this process. METHODS: Serial high-resolution SWI was acquired on 17
      patients with high-grade glioma between 8 months and 4.5 years posttreatment with
      RT and adjuvant chemotherapy. Nine of these patients were also treated with the
      anti-angiogenic agent enzastaurin. Microbleeds were identified as discrete foci
      of susceptibility not corresponding to vessels, tumor, or postoperative infarct,
      and counted in normal-appearing brain. Analysis of covariance was performed to
      compare slopes of regression of individual patients' microbleed counts over time,
      Wilcoxon rank-sum tests examined significant differences in rates of microbleed
      formation between groups, and linear and quadratic mixed-effects models were
      employed. RESULTS: The number of microbleeds increased with time for all
      patients, with initial onset occurring at 8-22 months. No microbleeds disappeared
      once formed. The average rate of microbleed formation significantly increased
      after 2 years post-RT (P < .001). Patients receiving anti-angiogenic therapy
      exhibited fewer microbleeds overall (P < .05) and a significant reduction in
      initial rate of microbleed appearance (P = .01). CONCLUSIONS: We have
      demonstrated a dramatic increase in microbleed formation after 2 years post-RT
      that was decelerated by the concomitant administration of anti-angiogenic
      therapy, which may aid in determining brain regions susceptible to RT.

PMID- 26206775
TI  - RhoB upregulation leads to either apoptosis or cytostasis through differential
      target selection.
AB  - Anaplastic thyroid carcinoma is a highly aggressive undifferentiated carcinoma
      with a mortality rate near 100% due to an assortment of genomic abnormalities
      which impede the success of therapeutic options. Our laboratory has previously
      identified that RhoB upregulation serves as a novel molecular therapeutic target
      and agents upregulating RhoB combined with paclitaxel lead to antitumor synergy.
      Knowing that histone deacetylase 1 (HDAC1) transcriptionally suppresses RhoB, we
      sought to extend our findings to other HDACs and to identify the HDAC inhibitor
      (HDACi) that optimally synergize with paclitaxel. Here we identify HDAC6 as a
      newly discovered RhoB repressor. By using isoform selective HDAC inhibitors
      (HDACi) and shRNAs, we show that RhoB has divergent downstream signaling
      partners, which are dependent on the HDAC isoform that is inhibited. When RhoB
      upregulates only p21 (cyclin kinase inhibitor) using a class I HDACi
      (romidepsin), cells undergo cytostasis. When RhoB upregulates BIMEL using class
      II/(I) HDACi (belinostat or vorinostat), apoptosis occurs. Combinatorial synergy
      with paclitaxel is dependent upon RhoB and BIMEL while upregulation of RhoB and
      only p21 blocks synergy. This bifurcated regulation of the cell cycle by RhoB is
      novel and silencing either p21 or BIMEL turns the previously silenced pathway on,
      leading to phenotypic reversal. This study intimates that the combination of
      belinostat/vorinostat with paclitaxel may prove to be an effective therapeutic
      strategy via the novel observation that class II/(I) HDACi antagonize HDAC6
      mediated suppression of RhoB and subsequent BIMEL, thereby promoting antitumor
      synergy. These overall observations may provide a mechanistic understanding of
      optimal therapeutic response. 

PMID- 26206776
TI  - 4-IPP, a selective MIF inhibitor, causes mitotic catastrophe in thyroid
      carcinomas.
AB  - Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that
      is over-expressed in several human neoplastic cells. When MIF binds its receptor
      (CD74) and co-receptor (CD44), it initiates signaling cascades that orchestrate
      cell proliferation and survival, and it can directly modulate the activity of
      AMPK. These activities indicate that MIF potentially regulates cell survival and
      metabolism. We found that MIF was primarily co-expressed with CD74 in 16 out of
      23 papillary thyroid carcinoma (PTC) and in all the 27 available anaplastic
      thyroid carcinoma (ATC) biopsy samples. MIF and CD74 were co-expressed in TPC-1
      and HTC-C3 cell lines. The selective MIF inhibitor, 4-iodo-6-phenylpyrimidine (4
      IPP), blocked MIF/CD74 internalization, activated JNK, and dose-dependently
      inhibited proliferation inducing apoptosis and mitotic cell death. In two CD74
      negative cell lines, NIM-1 and K1, 4-IPP treatment partially reduced
      proliferation. Coordinated MIF and CD74 expression appeared to confer in tumor
      cells the plasticity necessary to escape cell cycle regulation, metabolic
      changes, and stress conditions. MIF/CD74 signaling removal made cells susceptible
      to apoptosis and mitotic cell death. This finding suggests a possible avenue for
      targeting DNA endoreduplication, thus preventing the proliferation of therapy
      resistant cell subpopulations. This study highlights MIF/CD74 axis as an
      important player in the biology of aggressive thyroid neoplasms. 

PMID- 26206778
TI  - A hitherto unrecognised case of progressive multifocal leukoencephalopathy.
AB  - A 65-year-old man presented with a 6-week history of increasing confusion with
      associated cognitive decline. Empirical antibiotic cover for a urinary tract
      infection was prescribed with no response. After exhaustive radiological and
      pathological investigations were carried out, a diagnosis of John Cunningham
      virus encephalopathy was made. This case report describes the varied clinical
      presentation of symptoms and their management options, along with the latest
      clinical opinions behind them. 

PMID- 26206779
TI  - Van der Knaap disease: a rare disease with atypical features.
AB  - Megalencephalic leukoencephalopathy with subcortical cysts (MLC), or Van der
      Knaap disease, is a rare autosomal recessive disorder. It is characterised by
      macrocephaly that either presents at birth or develops during infancy. It occurs
      more commonly in some ethnicities where consanguinity is common, such as in the
      Agrawal community in India. This disease typically presents with a history of
      delayed motor milestones in affected children. MRI findings including
      leukodystrophy and subcortical cysts are hallmarks of the disease and yield the
      diagnostic clue in most cases. Several cases of Van der Knaap disease with
      classical features have been reported in the literature. We present a case of Van
      der Knaap disease with classical MRI features, including a few distinctly
      atypical characteristics in its epidemiological, clinical and
      electrophysiological attributes. 

PMID- 26206780
TI  - Fungal endophthalmitis: an unusual complication of GI surgery and endoluminal
      vacuum therapy.
AB  - We present a case of endogenous fungal endophthalmitis arising as a complication
      of fungal septicaemia following gastrointestinal surgery, and subsequent
      treatment with endoluminal vacuum therapy (Endo-SPONGE, B Braun Medical Ltd). Our
      patient developed a pre-sacral collection due to an anastomotic leak post
      ileoanal pouch formation. Despite treatment with Endo-sponges and antibiotics,
      the patient suffered recurrent sepsis and the cavity failed to reduce in size. He
      developed red eyes and blurred vision, leading to the diagnosis of fungal
      endophthalmitis. Extended fungal cultures of the Endo-sponges and pouch effluent
      revealed Candida spp. This case is the first report of fungal endophthalmitis
      associated with Endo-sponge use and highlights the importance of fungal cultures
      in patients with ongoing sepsis. 

PMID- 26206781
TI  - Progressive wheeze: atrial myxoma masquerading as chronic obstructive pulmonary
      disease.
AB  - Atrial myxoma, the commonest primary cardiac neoplasm, presents with symptoms of
      heart failure, embolic phenomena or constitutional upset. We present an atypical
      case, with wheeze and symptomatic exacerbations typical of chronic obstructive
      pulmonary disease. With no early clinical evidence of heart failure, the patient
      was managed with inhaled steroids and bronchodilators, with little relief. Only
      when the patient was in extremis requiring intubation, due to respiratory
      failure, did clinical evidence of left heart failure become apparent, with
      echocardiography demonstrating a massive left atrial myxoma obstructing the
      mitral valve annulus. Following successful surgical resection, the patient's
      symptoms fully abated. This case highlights the importance of considering cardiac
      wheeze in those initially managed as obstructive airway disease not responding in
      a typical fashion to initial bronchodilator therapy, and particularly in those
      with rapidly progressive symptoms. Such patients should be referred early for
      cardiac imaging. The excellent prognosis and quick recovery after timely surgical
      resection of a myxoma are also highlighted. 

PMID- 26206777
TI  - The mammary stem cell hierarchy: a looking glass into heterogeneous breast cancer
      landscapes.
AB  - The mammary gland is a dynamic organ that undergoes extensive morphogenesis
      during the different stages of embryonic development, puberty, estrus, pregnancy,
      lactation and involution. Systemic and local cues underlie this constant tissue
      remodeling and act by eliciting an intricate pattern of responses in the mammary
      epithelial and stromal cells. Decades of studies utilizing methods such as
      transplantation and lineage-tracing have identified a complex hierarchy of
      mammary stem cells, progenitors and differentiated epithelial cells that fuel
      mammary epithelial development. Importantly, these studies have extended our
      understanding of the molecular crosstalk between cell types and the signaling
      pathways maintaining normal homeostasis that often are deregulated during
      tumorigenesis. While several questions remain, this research has many
      implications for breast cancer. Fundamental among these are the identification of
      the cells of origin for the multiple subtypes of breast cancer and the
      understanding of tumor heterogeneity. A deeper understanding of these critical
      questions will unveil novel breast cancer drug targets and treatment paradigms.
      In this review, we provide a current overview of normal mammary development and
      tumorigenesis from a stem cell perspective. 

PMID- 26206782
TI  - Colistin neurotoxicity: revisited.
AB  - The revival of polymyxin antibiotics with the advent of multidrug resistant gram
      negative bacteria in the recent decade has led to renewed interest in toxicity of
      this indispensable drug. We report a postoperative case of burst abdomen where
      colistin was started in view of Pseudomonas organism sensitive to colistin.
      Subsequently, the patient went into respiratory depression and encephalopathy
      after starting the treatment. She recovered promptly after stopping the drug. 

PMID- 26206783
TI  - Emphysematous cystitis-gas in bladder: a rare urological emergency.
AB  - Emphysematous cystitis is an unusual inflammatory condition characterised by the
      presence of air within the bladder wall and lumen. It is usually seen in patients
      with diabetes, and in those with long-term catheterisation or of
      immunocompromised status. Its presentation varies from asymptomatic to frank
      urosepsis. It is diagnosed after radiological studies. Treatment requires
      establishment of prompt urinary drainage, antibiotic coverage and correction of
      offending factors, if any. We report a case of 41-year-old, non-diabetic,
      otherwise healthy woman presenting with lower urinary tract symptoms with
      pneumaturia, which was managed conservatively. A review of the recent literature
      is also presented. 

PMID- 26206784
TI  - Spontaneous multisystem deep venous thrombosis as an unusual presentation of
      Behcet's disease in a young Afro-Caribbean patient.
AB  - Behcet's disease is an autoimmune mediated multisystem vasculitis. It is most
      prevalent in Middle Eastern and Mediterranean patients and considered rare in
      Afro-Caribbean populations. The disease phenotype in Afro-Caribbean patients is
      more severe with systemic involvement, in particular lesions affecting the
      vascular system known as angio-Behcet's. The archetypal triad of disease in
      Behcet's includes oral stomatitis, genital ulceration and ocular lesions,
      however, the variety of symptoms patients experience is recognised by the revised
      International Criteria for Behcet's disease and is reflected in the clinical
      scoring criteria. The authors report an unusual case of Behcet's disease in a
      young Afro-Caribbean patient presenting with spontaneous bilateral renal,
      cerebral and pulmonary venous thrombosis as first presentation. Physicians should
      be aware of the aggressive and atypical manner in which Behcet's can present in
      Afro-Caribbean patients in order to avoid diagnostic delay and remain vigilant
      for thromboembolic lesions in this population. 

PMID- 26206785
TI  - Soft tissue mass of the calf as the presenting symptom of primary carcinoma of
      the lung.

PMID- 26206786
TI  - Concordant chromosome 3 results in paired choroidal melanoma biopsies and
      subsequent tumour resection specimens.
AB  - BACKGROUND/AIM: The study's aim was to compare chromosome 3 aberrations of
      choroidal melanoma (CM) as determined by multiplex ligation dependent probe
      amplification (MLPA) or microsatellite analysis (MSA) in intraocular tumour
      biopsies with those results obtained from subsequent endoresection/enucleation of
      the same CM. METHODS: A retrospective cohort of 28 patients with CM seen between
      2007 and 2014 at the Liverpool Ocular Oncology Centre was analysed. Prognostic
      genetic testing, for chromosome 3 status, was performed on all tumour specimens,
      either by MLPA or MSA, depending on DNA yield. In nine cases genetic testing was
      performed on a sample taken after radiotherapy; four of these had genetic
      information pre- and post-radiotherapy. RESULTS: Fourteen biopsy specimens were
      analysed by MLPA and 14 by MSA. Twenty-seven endoresection or enucleation
      specimens were analysed by MLPA, and a single enucleation specimen by MSA.
      Chromosome 3 data showed prognostic concordance for the patient-matched samples
      in all 28 cases including 4 cases where samples were taken pre pre- and post
      radiotherapy. Thirteen cases were classified as monosomy 3 and 12 as disomy 3.
      Two cases had a loss of chromosome arm 3q in both samples and a single case
      showed loss of 3p in the biopsy sample with complete monosomy 3 in the subsequent
      enucleation sample taken 5 months later. CONCLUSIONS: Intraocular biopsy of CM
      yields similar prognostic information to larger surgical specimens. Initial
      evidence, that genetic testing can be successfully conducted post radiotherapy,
      is also provided. TRIAL REGISTRATION NUMBER: NITRO trial, ISRCTN35236442.

PMID- 26206787
TI  - The effect of consumption of ethanol on subfoveal choroidal thickness in acute
      phase.
AB  - BACKGROUND/AIMS: To investigate the acute effect of ethanol consumption on
      subfoveal choroidal thickness. METHODS: This prospective interventional study
      included the right eyes of 30 healthy subjects (30 eyes). Ethanol (1.0 g/kg) was
      administered orally on the first visit. A matching volume of water was
      administered orally on the second visit. Oral administration of ethanol and water
      was performed at 14:00, and choroidal thickness was measured every 30 min until
      16:00. Change of choroidal thickness after oral administration of ethanol and
      water was the main outcome measure. RESULTS: At baseline, choroidal mean
      subfoveal thickness was 299.0+/-73.4 um (range, 186.5-472.5 um) before ethanol
      consumption and 297.1+/-71.1 um (range, 187.0-470.5 um) before water consumption.
      After consumption of ethanol, mean subfoveal choroidal thickness increased during
      the first 60 min and then decreased during the next 60 min, which was a
      significant change over time (p<0.001). After consumption of water, there was no
      significant change in mean subfoveal choroidal thickness over time (p=0.310).
      Comparison of changes in the mean subfoveal choroidal thickness during 120 min
      showed significant difference between ethanol and water consumption (p<0.001).
      CONCLUSIONS: The results of current study show that consumption of ethanol
      significantly affected the choroidal thickness. Mean subfoveal choroidal
      thickness increased during the first 60 min and then decreased during the next
      120 min after ethanol consumption.

PMID- 26206788
TI  - En face mode of swept-source optical coherence tomography in circumscribed
      choroidal haemangioma.
AB  - PURPOSE: To describe the findings in circumscribed choroidal haemangioma (CCH)
      using en face swept-source optical coherence tomography (SS-OCT). METHODS: En
      face images were obtained employing DRI-1 Atlantis OCT (Topcon, Tokyo, Japan),
      using a three-dimensional volumetric scan of 12*9 mm. Images were obtained from
      the retinal pigment epithelium to 1000 MUm in depth of the tumour. RESULTS:
      Twenty-two eyes from 22 patients with the clinical diagnosis of CCH were
      included. In 20 eyes (90.9%), a characteristic pattern was visualised in the en
      face image across the vascular tumour. A multilobular pattern, similar to a
      honeycomb, with hyporeflective, confluent, oval or round areas corresponding with
      the lumen of the tumour vascular spaces, and hyper-reflective zones, which may
      represent the vessels walls and connective tissue of the tumour. Ten eyes (45.4%)
      showed a hyper-reflective halo surrounding the tumour. Seventeen tumours (77.2%)
      showed small diameter vessels at the inner zone and larger vessels in the outer
      area. Twelve patients (54.5%) had previously received treatment (photodynamic
      therapy, transpupillary thermotherapy, dexamethasone intravitreal implant or
      brachytherapy with ruthenium-106). No differences were found between treated and
      untreated patients in any of the measured parameters. CONCLUSIONS: En face SS-OCT
      is a rapid, non-invasive, high-resolution, technology, which allows a
      complementary study to cross-sectional scans in CCH. A characteristic
      multilobular pattern, with a hyper-reflective halo surrounding the tumour, was
      found in en face SS-OCT images. No morphological differences were found between
      naive patients and patients who received previous treatment.

PMID- 26206789
TI  - Boston type 1 keratoprosthesis for primary congenital glaucoma.
AB  - BACKGROUND/AIMS: To evaluate the Boston type 1 keratoprosthesis (KPro-1) in
      treatment of eyes with primary congenital glaucoma. METHODS: A retrospective
      review was performed of every eye with congenital glaucoma that was treated with
      a KPro-1 at a tertiary eye care centre between 1 January 2008 and 1 July 2014.
      The main outcome measures were visual outcome, prosthesis retention and
      postoperative complications. RESULTS: Six eyes of six patients met the inclusion
      criteria. This included two paediatric patients, aged 6 months and 6 years, and
      four adults who were 27-33 years of age. Preoperatively, the best corrected
      visual acuity (BCVA) was worse than 20/400 in every eye. Three eyes had hand
      motions and one eye had light perception vision. After a mean follow-up period of
      31 months (range 16-51 months), three eyes (50.0%) had a BCVA that was >=20/400.
      Overall, the BCVA improved in four eyes (66.7%), and remained the same in two
      eyes (33.3%). The device was retained in six eyes (83.3%). One or more
      complications occurred in five eyes (83.3%) and included sterile corneal
      ulceration (three eyes), retroprosthetic membrane formation (three eyes),
      progressive glaucomatous optic neuropathy (two eyes), device extrusion (one eye)
      and an epiretinal membrane (one eye). CONCLUSIONS: The Boston KPro-1 has an
      excellent prognosis for retention in eyes with congenital glaucoma. The visual
      prognosis remains guarded due to the high prevalence of pre-existing ocular
      comorbidity and the common occurrence of sight-threatening postoperative
      complications.

PMID- 26206790
TI  - Prevalence and characteristics of hyporeflective preretinal tissue in
      vitreomacular interface disorders.
AB  - AIMS: To assess prevalence and characteristics of hyporeflective preretinal
      tissue on spectral domain optical coherence tomography (SDOCT) in eyes with
      vitreomacular interface disorders. METHODS: 4037 eyes (3195 patients) with
      diagnosis of lamellar macular hole (LMH), full-thickness macular hole (FTMH),
      epiretinal membrane (ERM) and vitreomacular traction were included. Quantitative
      analysis was performed including volume and area of the epiretinal proliferation,
      as well as the brightness of the hyporeflective band. Clinical characteristics
      were also collected and analysed. RESULTS: A hyporeflective preretinal tissue
      layer was identified in 204 of 4037 eyes (5.1%); 162 eyes in LMH (79.4%), 23 eyes
      in FTMH (11.3%) and 19 eyes in ERM (9.3%). In LMH, the visual acuity was
      significantly different between the cases with and without epiretinal
      proliferation at the initial visit and the final visit, (p=0.012, 0.046,
      respectively). The maximum thickness, area, volume of hyporeflective preretinal
      tissue became significantly larger during the observation period (p<0.001).
      Brightness of the preretinal tissue (109.3+/-21.1 arbitrary unit) was close to
      the retinal ganglion cell layer (112.0+/-19.5) and the retinal outer plexiform
      layer (117.7+/-19.5). CONCLUSIONS: Hyporeflective preretinal tissue was found
      with significant frequency in eyes with LMH, FTMH and ERM, with a particularly
      high incidence in LMH. The increased presence of this tissue in cases of LMH may
      signify a particular subtype of LMH. More research is needed to better understand
      the implications of the presence of this tissue for visual and surgical outcomes.

PMID- 26206791
TI  - Vector analysis of astigmatic correction after small-incision lenticule
      extraction and femtosecond-assisted LASIK for low to moderate myopic astigmatism.
AB  - AIM: To compare astigmatic correction between femtosecond-assisted laser in situ
      keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). METHODS:
      A total of 111 patients were included in this prospective study. Fifty-seven eyes
      were treated with LASIK and 54 eyes were treated with SMILE for myopia with low
      to moderate (-0.25 to -4.0 D) astigmatism. Uncorrected distance visual acuity
      (UDVA), corrected distance visual acuity and manifest refraction were measured
      preoperatively and at 1 and 3 months postoperatively. Visual and refractive
      outcomes were reported. Changes in refractive astigmatism were evaluated using
      vector analysis. RESULTS: Preoperative characteristics were similar between both
      groups. The UDVA at 1 and 3 months was better in the LASIK group compared with
      the SMILE group (p<0.009). Postoperative cylinder was higher in the SMILE group
      (p<0.001). Fewer eyes attained the attempted cylindrical correction in the SMILE
      group (p<0.029). Vector analysis showed no significant difference in target
      induced astigmatism (p=0.091) and angle of error (p>0.596) between the two
      groups. Surgically induced astigmatism was significantly lower in the SMILE group
      (p<0.023), while the difference vector (p<0.001) and absolute angle of error
      (p<0.016) were significantly higher in the SMILE group. No significant difference
      was found in these parameters between 1 and 3 months in both groups (p>0.122).
      CONCLUSIONS: Our results showed that SMILE offered a less favourable astigmatic
      correction comparable to femtosecond-assisted LASIK in eyes with low to moderate
      myopic astigmatism. The alignment of treatment was more variable in SMILE,
      leading to a lower efficacy compared with LASIK by 3 months postoperatively.

PMID- 26206792
TI  - Rapid Identification and Quantification of Natural Antioxidants in the Seeds of
      Rhubarb from Different Habitats in China Using Accelerated Solvent Extraction and
      HPLC-DAD-ESI-MSn-DPPH Assay.
AB  - In this study, the 10 accessions of rhubarb seeds from different habitats in
      China were investigated. Lipids were removed using petroleum ether, and the
      effective components were then separated using accelerated solvent extraction
      with 80% aqueous methanol. An off-line 2,2-diphenyl-1-picrylhydrazyl (DPPH) free
      radical scavenging method was used as the marker to evaluate the total
      antioxidant capability of extracts. On-line high-performance liquid
      chromatography-diode-array detectors-electrospray ionization-tandem mass
      spectrometry (HPLC-DAD-ESI-MS(n)) and HPLC-DAD-DPPH assays were developed for
      rapid identification and quantification of individual free-radical scavengers in
      extracts of rhubarb seeds. Ten free-radical scavengers from methanolic extracts
      of the rhubarb seeds were screened, five of which were identified and
      quantitatively analyzed: epicatechin, myricetin, hyperoside, quercitrin and
      quercetin. All were identified in rhubarb seeds for the first time and can be
      regarded as the major potent antioxidants in rhubarb seeds due to representing
      most of the total free-radical scavenging activity. Preliminary analysis of
      structures was performed for another five antioxidants. Based on our validation
      results, the developed method can be used for rapid separation, convenient
      identification and quantification of the multiple antioxidative constituents in
      rhubarb seeds, featuring good quantification parameters, accuracy and precision.
      The results are important to clarify the material basis and therapeutic mechanism
      of rhubarb seeds. 

PMID- 26206793
TI  - A Self-Regulation Model of Sexual Grooming.
AB  - A preparatory process is widely accepted to be a common feature in the
      perpetration of sexual offenses. Numerous commentators, however, have documented
      the difficulties in defining and understanding this process, given its transient
      nature and its specificity to this one form of criminal behavior. This
      theoretical review aims to provide a universal model of a grooming process for
      the achievement of illicit or illegal goals in which achievement requires the
      compliance or submission of another individual-one that can be applied both to
      the sexual offending process and beyond. First, an evaluation of three process
      models of grooming is conducted. Second, using a process of theory knitting, an
      integrated universal model of illicit grooming is developed. This model unites
      salient elements of the previous models while seeking to address their
      limitations. It is founded in control theory and self-regulation approaches to
      behavior, assumes a goal-directed protagonist, and comprises two distinct phases,
      namely, (1) a potentiality phase of rapport-building, incentivization,
      disinhibition, and security-management and (2) a disclosure phase in which goal
      relevant information is introduced in a systematic and controlled manner in order
      to desensitize the target. Finally, the theoretical quality of the model is
      appraised, and its clinical implications are discussed.

PMID- 26206794
TI  - Assessing Adult Exposure to Community Violence: A Review of Definitions and
      Measures.
AB  - OBJECTIVE: Although experiences of community violence are linked with negative
      outcomes for adults and children, few standardized measures assessing community
      violence exist, and available measures lack consistency concerning the definition
      of community violence. Further, most measures currently utilized to assess adult
      exposure to community violence were designed for use with children and
      adolescents. To address these identified concerns and make recommendations for
      future research, this article reviews contemporary definitions of community
      violence, identifies the outcomes of exposure to community violence for adults,
      and evaluates measures of exposure to community violence with published
      psychometric data employing adult samples. METHOD: A systematic review of the
      literature was conducted to identify studies that (1) included a self-report of
      community violence exposure, (2) included primarily adult respondents, and (3)
      reported psychometric data. RESULTS: Seventeen studies met the inclusion
      criteria. Measures employed in these studies were reviewed and basic psychometric
      properties discussed. Notably, the Survey of Exposure to Community Violence was
      the most commonly used measure among these studies. CONCLUSIONS: Although
      multiple measures demonstrated limited but acceptable psychometric performance in
      select studies, few in-depth psychometric analyses exist for measures of adult
      exposure to community violence. Also, it is difficult to compare studies due to
      variations in definitions of community violence and multiple versions of each
      measure. Recommendations for future research include provision of explicit
      definitions of community violence and reporting psychometric data for measures.

PMID- 26206795
TI  - The Nature of Instrumentality and Expressiveness of Homicide Crime Scene
      Behaviors: A Review.
AB  - Homicide offender typologies developed based on crime scene behaviors have
      practical utility for scholarly and criminal investigative endeavors. Hence,
      there has been an increasing interest to develop empirical and testable offender
      typologies. Specifically, the present study offers a review of the
      instrumental/expressive offender dichotomy, which is developed primarily based on
      the analysis of (nonsexual) homicide crime scene behaviors. The validity of the
      instrumental/expressive dichotomy of homicide offenders have been supported by
      various studies that sampled population from different countries. In addition,
      the extant literature indicates that the instrumental and expressive categories
      could further be expressed in different subthemes or dimensions. Implications for
      practice in the aspect of suspect prioritization as well as for research are
      discussed.

PMID- 26206796
TI  - Therapeutic effect of androgen therapy in a mouse model of aplastic anemia
      produced by short telomeres.
AB  - Aplastic anemia is a rare but life-threatening disorder characterized by
      cytopenia in at least two of the three blood lineages. A frequent feature of
      patients with aplastic anemia is that they have shorter telomeres than those of
      age-matched controls. Testosterone has been used for over half a century in the
      treatment of aplastic anemia. However, although remissions are frequent following
      hormone therapy, the molecular mechanism underlying the response to treatment has
      remained unknown. Here we explored the possibility that the recently described
      regulation of telomerase activity by sex hormones may be the mechanism
      responsible. To this end, we used a mouse model of aplastic anemia induced by
      short telomeres in the bone marrow compartment. We found that testosterone
      therapy results in telomerase up-regulation, improved blood counts, and a
      significant extension of life-span of these mice. Importantly, longitudinal
      follow-up studies revealed longer telomeres in peripheral blood in mice subjected
      to hormone treatment. Our results demonstrate that testosterone-mediated
      telomerase activation can attenuate or reverse aplastic anemia disease
      progression associated with the presence of short telomeres. 

PMID- 26206797
TI  - Epidemiology of invasive fungal disease in lymphoproliferative disorders.

PMID- 26206798
TI  - Genetic variants and cell-free hemoglobin processing in sickle cell nephropathy.
AB  - Intravascular hemolysis and hemoglobinuria are associated with sickle cell
      nephropathy. ApoL1 is involved in cell-free hemoglobin scavenging through
      association with haptoglobin-related protein. APOL1 G1/G2 variants are the
      strongest genetic predictors of kidney disease in the general African-American
      population. A single report associated APOL1 G1/G2 with sickle cell nephropathy.
      In 221 patients with sickle cell disease at the University of Illinois at
      Chicago, we replicated the finding of an association of APOL1 G1/G2 with
      proteinuria, specifically with urine albumin concentration (beta=1.1, P=0.003),
      observed an even stronger association with hemoglobinuria (OR=2.5, P=4.3*10(-6)),
      and also replicated the finding of an association with hemoglobinuria in 487
      patients from the Walk-Treatment of Pulmonary Hypertension and Sickle cell
      Disease with Sildenafil Therapy study (OR=2.6, P=0.003). In 25 University of
      Illinois sickle cell disease patients, concentrations of urine kidney injury
      molecule-1 correlated with urine cell-free hemoglobin concentrations (r=0.59,
      P=0.002). Exposing human proximal tubular cells to increasing cell-free
      hemoglobin led to increasing concentrations of supernatant kidney injury molecule
      1 (P=0.01), reduced viability (P=0.01) and induction of HMOX1 and SOD2. HMOX1
      rs743811 associated with chronic kidney disease stage (OR=3.0, P=0.0001) in the
      University of Illinois cohort and end-stage renal disease (OR=10.0, P=0.0003) in
      the Walk-Treatment of Pulmonary Hypertension and Sickle cell Disease with
      Sildenafil Therapy cohort. Longer HMOX1 GT-tandem repeats (>25) were associated
      with lower estimated glomerular filtration rate in the University of Illinois
      cohort (P=0.01). Our findings point to an association of APOL1 G1/G2 with kidney
      disease in sickle cell disease, possibly through increased risk of
      hemoglobinuria, and associations of HMOX1 variants with kidney disease, possibly
      through reduced protection of the kidney from hemoglobin-mediated toxicity. 

PMID- 26206800
TI  - Tandem autologous-allogeneic stem cell transplantation as a feasible and
      effective procedure in high-risk lymphoma patients.

PMID- 26206801
TI  - Use of killer cell immunoglobulin-like receptor genes as early markers of
      hematopoietic chimerism after double-umbilical cord blood transplantation.

PMID- 26206799
TI  - Targeted sequencing identifies associations between IL7R-JAK mutations and
      epigenetic modulators in T-cell acute lymphoblastic leukemia.
AB  - T-cell acute lymphoblastic leukemia is caused by the accumulation of multiple
      oncogenic lesions, including chromosomal rearrangements and mutations. To
      determine the frequency and co-occurrence of mutations in T-cell acute
      lymphoblastic leukemia, we performed targeted re-sequencing of 115 genes across
      155 diagnostic samples (44 adult and 111 childhood cases). NOTCH1 and CDKN2A/B
      were mutated/deleted in more than half of the cases, while an additional 37 genes
      were mutated/deleted in 4% to 20% of cases. We found that IL7R-JAK pathway genes
      were mutated in 27.7% of cases, with JAK3 mutations being the most frequent event
      in this group. Copy number variations were also detected, including deletions of
      CREBBP or CTCF and duplication of MYB. FLT3 mutations were rare, but a novel
      extracellular mutation in FLT3 was detected and confirmed to be transforming.
      Furthermore, we identified complex patterns of pairwise associations, including a
      significant association between mutations in IL7R-JAK genes and epigenetic
      regulators (WT1, PRC2, PHF6). Our analyses showed that IL7R-JAK genetic lesions
      did not confer adverse prognosis in T-cell acute lymphoblastic leukemia cases
      enrolled in the UK ALL2003 trial. Overall, these results identify
      interconnections between the T-cell acute lymphoblastic leukemia genome and
      disease biology, and suggest a potential clinical application for JAK inhibitors
      in a significant proportion of patients with T-cell acute lymphoblastic leukemia.

PMID- 26206802
TI  - Antineoplastic effects of liposomal short interfering RNA treatment targeting
      BLIMP1/PRDM1 in primary effusion lymphoma.

PMID- 26206803
TI  - MB4-2 breakpoint in MMSET combined with del(17p) defines a subset of t(4;14)
      multiple myeloma with very poor prognosis.

PMID- 26206804
TI  - Too much guidance.

PMID- 26206805
TI  - Treatment of wide-necked basilar tip aneurysm not amenable to Y-stenting using
      the PulseRider device.
AB  - Endovascular treatment of broad-necked bifurcation aneurysms remains challenging.
      Stent-assisted coiling has been successful but requires catheterization of the
      branches off the parent vessel. We present the case of a patient who failed
      primary and stent-assisted coiling of a large basilar tip aneurysm because the
      morphology of the aneurysm precluded successful distal catheterization of the
      posterior cerebral artery (PCA) branches. Using the PulseRider device, which does
      not require catheterization of bifurcation branches, we were able to treat the
      aneurysm successfully. 

PMID- 26206806
TI  - Platelet function testing: does a randomized controlled trial settle the debate?

PMID- 26206807
TI  - Significance of Development and Reversion of Collaterals on MRI in Early
      Neurologic Improvement and Long-Term Functional Outcome after Intravenous
      Thrombolysis for Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Predicting response to rtPA is essential in the era of
      endovascular therapy for stroke. The purpose of this study was to elucidate
      prognostic factors of early neurologic improvement and long-term outcome with
      respect to the development and reversion of leptomeningeal collaterals in
      recanalization therapy after acute ischemic stroke. MATERIALS AND METHODS: We
      analyzed consecutive patients with proximal MCA occlusion treated with rtPA from
      2007 to 2012 at 2 hospital stroke centers. All patients routinely underwent brain
      MR imaging before rtPA. To assess the reversion of collateral signs, we included
      patients who underwent follow-up MR imaging. We assessed the development and
      reversion of collaterals by using a combination of 2 MR imaging collateral
      markers, the hyperintense vessel sign and the posterior cerebral artery
      laterality sign. Early neurologic improvement was defined as a decrease in the
      NIHSS score of >=10 or a score of <=2 at 24 hours of treatment. RESULTS: Early
      neurologic improvement was observed in 22 of 48 eligible patients. The
      development of collaterals at arrival (15/22 versus 9/26, P = .042) was
      significantly associated with early neurologic improvement. Multivariate analysis
      adjusting for other variables showed that the development of collaterals at
      arrival (OR, 4.82; 95% CI, 1.34-19.98; P = .015) was independently associated
      with early neurologic improvement. Reversion of collaterals was significantly
      associated with successful recanalization (P < .001), and multivariate analysis
      showed that the reversion of collaterals was an independent prognostic factor of
      long-term functional outcome (OR, 5.07; 95% CI, 1.38-22.09; P = .013).
      CONCLUSIONS: Our results indicate that the development of leptomeningeal
      collaterals plays a crucial role in achieving early neurologic improvement, and
      reversion of collaterals predicts a favorable outcome via arterial recanalization
      after rtPA treatment for acute stroke.

PMID- 26206808
TI  - Artery of the Superior Orbital Fissure: An Undescribed Branch from the
      Pterygopalatine Segment of the Maxillary Artery to the Orbital Apex Connecting
      with the Anteromedial Branch of the Inferolateral Trunk.
AB  - BACKGROUND AND PURPOSE: Some branches of the internal maxillary artery have
      anastomoses with the inferolateral trunk that are important as intracranial
      extracranial collateral pathways and as dangerous anastomoses for transarterial
      embolization of these branches. We present here an undescribed branch potentially
      anastomosing with the anteromedial branch of the inferolateral trunk, which is
      provisionally named the artery of the superior orbital fissure, defined as an
      arterial branch from the pterygopalatine segment of the maxillary artery to the
      orbital apex at the superior orbital fissure. MATERIALS AND METHODS: Two
      neuroradiologists reviewed 3D and MPR images of the external and/or common
      carotid artery with particular interest paid to the artery of the superior
      orbital fissure in 54 patients who underwent 3D angiography with a field of view
      covering the pterygopalatine fossa and the cavernous sinus. The underlying
      diseases in these patients were 17 parasellar hypervascular lesions (including 13
      cavernous sinus dural arteriovenous fistulas and 4 meningiomas), 18 internal
      carotid artery stenoses/occlusions, and 19 other diseases. RESULTS: The artery of
      the superior orbital fissure was identified in 20 of 54 patients; it arose at the
      pterygopalatine segment of the maxillary artery, either singly or from a common
      trunk with the artery of the foramen rotundum, and ran upward to reach the
      superior orbital fissure. It anastomosed with the anteromedial branch of the
      inferolateral trunk at the superior orbital fissure with blood flow toward the
      cavernous sinus (n = 14) and/or the ophthalmic artery (n = 2). It was more
      prominent in parasellar hypervascular lesions and internal carotid artery
      stenoses/occlusions than in other diseases. CONCLUSIONS: The artery of the
      superior orbital fissure, a remnant of the anastomotic artery, was often
      identified, especially in patients with parasellar hypervascular lesions.

PMID- 26206809
TI  - Glioma Angiogenesis and Perfusion Imaging: Understanding the Relationship between
      Tumor Blood Volume and Leakiness with Increasing Glioma Grade.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate imaging
      correlates to the changes occurring during angiogenesis in gliomas. This was
      accomplished through in vivo assessment of vascular parameters (relative CBV and
      permeability surface-area product) and their changing relationship with
      increasing glioma grade. MATERIALS AND METHODS: Seventy-six patients with gliomas
      underwent preoperative perfusion CT and assessment of relative CBV and
      permeability surface-area product. Regression analyses were performed to assess
      the rate of change between relative CBV and permeability surface-area product and
      to test whether these differed for distinct glioma grades. The ratio of relative
      CBV to permeability surface-area product was also computed and compared among
      glioma grades by using analysis of variance methods. RESULTS: The rate of change
      in relative CBV with respect to permeability surface-area product was highest for
      grade II gliomas followed by grade III and then grade IV (1.64 versus 0.91 versus
      0.27, respectively). The difference in the rate of change was significant between
      grade III and IV (P = .003) and showed a trend for grades II and IV (P = .098).
      Relative CBV/permeability surface-area product ratios were the highest for grade
      II and lowest for grade IV. The pair-wise difference among all 3 groups was
      significant (P < .001). CONCLUSIONS: There is an increase in relative CBV more
      than permeability surface-area product in lower grade gliomas, whereas in grade
      III and especially grade IV gliomas, permeability surface-area product increases
      much more than relative CBV. The rate of change of relative CBV with respect to
      permeability surface-area product and relative CBV/permeability surface-area
      product ratio can serve as an imaging correlate to changes occurring at the tumor
      microvasculature level.

PMID- 26206810
TI  - pCONus Device for the Endovascular Treatment of Wide-Neck Middle Cerebral Artery
      Aneurysms.
AB  - BACKGROUND AND PURPOSE: Endovascular treatment of bifurcation middle cerebral
      artery aneurysms with a wide neck could be challenging, and many lesions are
      still treated by a surgical approach. The pCONus is a newly emerging device for
      wide-neck bifurcation intracranial aneurysms. To date, a single report on the
      treatment of intracranial aneurysms including all locations has been published.
      We report our experience with pCONus in the treatment of wide-neck MCA aneurysms.
      MATERIALS AND METHODS: MCA aneurysms treated with pCONus in 4 European centers
      were retrospectively reviewed. RESULTS: Forty MCA aneurysms (mean dome size, 7.7
      mm; mean neck size, 5.6 mm) were treated in 40 patients (mean age, 62 years).
      Aneurysm coiling was performed after deployment of 1 pCONus in 95% (38/40) of
      cases and after deployment of 2 pCONus devices in 5% (2/40). No procedural
      angiographic complications were observed. Reversible neurologic complications
      were noted in 5% (2/40), and permanent neurologic complication, in 2.5% (1/40) at
      1 month. There was no mortality. No aneurysms bled or rebled after treatment.
      Immediate angiographic results were complete aneurysm occlusion in 25% (10/40),
      neck remnant in 47.5% (19/40), and aneurysm remnant in 27.5% (11/40). Follow-up
      (mean, 6.8 months) was available for 33 aneurysms (82.5%). Stable or improved
      results were observed in all except 3 cases, including 48.5% complete occlusions
      (16/33), 30.3% neck remnants (10/33), and 21.2% aneurysm remnants (7/33). There
      was no in-stent stenosis or jailed branch occlusion. There was no angiographic
      recurrence of initially totally occluded aneurysms. CONCLUSIONS: MCA aneurysms
      with a wide neck are amenable to treatment with pCONus.

PMID- 26206811
TI  - Effects of Type 2 Diabetes on Brain Structure and Cognitive Function: African
      American-Diabetes Heart Study MIND.
AB  - BACKGROUND AND PURPOSE: Rates of type 2 diabetes are higher among African
      Americans compared with individuals of European ancestry. The purpose of this
      investigation was to determine the relationship between MR imaging measures of
      brain structure (volume of GM, WM, WM lesions) and cognitive function in a
      population of African Americans with type 2 diabetes. These MR imaging measures
      of brain structure are affected by type 2 diabetes-associated macrovascular and
      microvascular disease and may be associated with performance on tasks of
      cognitive function in the understudied African American population. MATERIALS AND
      METHODS: African Americans with type 2 diabetes enrolled in the African American
      Diabetes Heart Study MIND study (n = 263) were evaluated across a broad range of
      cognitive domains and imaged with brain MR imaging. Associations between
      cognitive parameters and MR imaging measures of whole-brain GM, WM, and WM lesion
      volumes were assessed by using adjusted multivariate models. RESULTS: Lower GM
      volume was associated with poorer performance on measures of general cognitive
      function, working memory, and executive function. Higher WM lesion volume was
      associated with poorer performance on a smaller subset of cognitive domains
      compared with GM volume but included aspects of working memory and executive
      function. There were no statistically significant associations with WM volume.
      CONCLUSIONS: Markers of cortical atrophy and WM lesion volume are associated with
      cognitive function in African Americans with type 2 diabetes. These associations
      are described in an African American cohort with disease control similar to that
      of individuals of European ancestry, rather than underserved African Americans
      with poor access to health care. Interventions to reduce cortical atrophy and WM
      disease may improve cognitive outcomes in this understudied population.

PMID- 26206812
TI  - Additional Value of Intra-Aneurysmal Hemodynamics in Discriminating Ruptured
      versus Unruptured Intracranial Aneurysms.
AB  - BACKGROUND AND PURPOSE: Hemodynamics are thought to play an important role in the
      rupture of intracranial aneurysms. We tested whether hemodynamics, determined
      from computational fluid dynamics models, have additional value in discriminating
      ruptured and unruptured aneurysms. Such discriminative power could provide better
      prediction models for rupture. MATERIALS AND METHODS: A cross-sectional study was
      performed on patients eligible for endovascular treatment, including 55 ruptured
      and 62 unruptured aneurysms. Association with rupture status was tested for
      location, aneurysm type, and 4 geometric and 10 hemodynamic parameters. Patient
      specific spatiotemporal velocities measured with phase-contrast MR imaging were
      used as inflow conditions for computational fluid dynamics. To assess the
      additional value of hemodynamic parameters, we performed 1 univariate and 2
      multivariate analyses: 1 traditional model including only location and geometry
      and 1 advanced model that included patient-specific hemodynamic parameters.
      RESULTS: In the univariate analysis, high-risk locations (anterior cerebral
      arteries, posterior communicating artery, and posterior circulation), daughter
      sacs, unstable inflow jets, impingements at the aneurysm body, and unstable
      complex flow patterns were significantly present more often in ruptured
      aneurysms. In both multivariate analyses, only the high-risk location (OR, 3.92;
      95% CI, 1.77-8.68) and the presence of daughter sacs (OR, 2.79; 95% CI, 1.25
      6.25) remained as significant independent determinants. CONCLUSIONS: In this
      study population of patients eligible for endovascular treatment, we found no
      independent additional value of aneurysmal hemodynamics in discriminating rupture
      status, despite high univariate associations. Only traditional parameters (high
      risk location and the presence of daughter sacs) were independently associated
      with ruptured aneurysms.

PMID- 26206814
TI  - AIUM Practice Guideline for the Performance of Peripheral Venous Ultrasound
      Examinations.

PMID- 26206813
TI  - Progressive versus Nonprogressive Intracranial Dural Arteriovenous Fistulas:
      Characteristics and Outcomes.
AB  - BACKGROUND AND PURPOSE: A minority of intracranial dural arteriovenous fistulas
      progress with time. We sought to determine features that predict progression and
      define outcomes of patients with progressive dural arteriovenous fistulas.
      MATERIALS AND METHODS: We performed a retrospective imaging and clinical record
      review of patients with intracranial dural arteriovenous fistula evaluated at our
      hospital. RESULTS: Of 579 patients with intracranial dural arteriovenous
      fistulas, 545 had 1 fistula (mean age, 45 +/- 23 years) and 34 (5.9%) had
      enlarging, de novo, multiple, or recurrent fistulas (mean age, 53 +/- 20 years; P
      = .11). Among these 34 patients, 19 had progressive dural arteriovenous fistulas
      with de novo fistulas or fistula enlargement with time (mean age, 36 +/- 25
      years; progressive group) and 15 had multiple or recurrent but nonprogressive
      fistulas (mean age, 57 +/- 13 years; P = .0059, nonprogressive group). Whereas
      all 6 children had fistula progression, only 13/28 adults (P = .020) progressed.
      Angioarchitectural correlates to chronically elevated intracranial venous
      pressures, including venous sinus dilation (41% versus 7%, P = .045) and
      pseudophlebitic cortical venous pattern (P = .048), were more common in patients
      with progressive disease than in those without progression. Patients with
      progressive disease received more treatments than those without progression
      (median, 5 versus 3; P = .0068), but as a group, they did not demonstrate worse
      clinical outcomes (median mRS, 1 and 1; P = .39). However, 3 young patients died
      from intracranial venous hypertension and intracranial hemorrhage related to
      progression of their fistulas despite extensive endovascular, surgical, and
      radiosurgical treatments. CONCLUSIONS: Few patients with dural arteriovenous
      fistulas follow an aggressive, progressive clinical course despite treatment.
      Younger age at initial presentation and angioarchitectural correlates to venous
      hypertension may help identify these patients prospectively.

PMID- 26206815
TI  - AIUM Practice Guideline for the Performance of Diagnostic and Screening
      Ultrasound Examinations of the Abdominal Aorta in Adults.

PMID- 26206816
TI  - AIUM Practice Guideline for the Performance of an Ultrasound Evaluation of the
      Prostate (and Surrounding Structures).

PMID- 26206817
TI  - AIUM Practice Guideline for the Performance of Sonohysterography.

PMID- 26206818
TI  - AIUM Practice Guideline for the Performance of Scrotal Ultrasound Examinations.

PMID- 26206820
TI  - Vasospasm Surveillance With Transcranial Doppler Sonography in Subarachnoid
      Hemorrhage.
AB  - The use of transcranial Doppler monitoring for the diagnosis of vasospasm in
      subarachnoid hemorrhage is backed by national guidelines. However, it remains
      poorly used across neurologic intensive care units in the United States. This
      current practice article uses 2 clinical vignettes to illustrate the simplicity
      and logic behind routine daily surveillance of vasospasm with transcranial
      Doppler sonography in patients with subarachnoid hemorrhage, in preference to
      other modalities. 

PMID- 26206821
TI  - Correlation of Hemorrhage Near Developing Opossum Skull With Pulsed Ultrasound
      Exposure Parameters.
AB  - OBJECTIVES: High-intensity focused ultrasound (HIFU) has been used noninvasively
      for therapeutic applications. Before HIFU can be used therapeutically on a human
      fetus, the bioeffects related to HIFU must be studied, and the mechanism causing
      the bioeffects should be understood. Previous studies have shown that HIFU, when
      targeted on fetal rat and mice bones. resulted in hemorrhage. However, the
      mechanism responsible has not been identified. In this study, we looked at
      ultrasound parameters related to hemorrhage in an effort to better understand the
      mechanism. METHODS: Brazilian opossum pups (7-8 postnatal days) were exposed to a
      1.1-MHz f/1 spherically focused transducer (6.3 cm focal length). Four treatment
      groups of n = 14 and a control group of n = 14 were exposed to rarefactional
      pressures of 3.6 to 6 MPa with spatial-peak temporal average intensity values of
      5.4 to 10.8 W/cm(2). The pulse repetition frequency was varied from 500 to 1000
      Hz with exposure durations of 1 to 4 minutes. RESULTS: Four groups with sample
      sizes of 14 had hemorrhage percentages of 43%, 36%, 29%, and 36%, respectively.
      Hemorrhage occurrence and size were found to correlate strongly with the
      nonlinear product of energy density and number of pulses, with correlation values
      of 0.92 and 0.97, respectively. CONCLUSIONS: The dependence of hemorrhage on
      energy density and the number of pulses suggests that the hemorrhage may be due
      to high-stress, low-cycle mechanical fatigue damage. Hence, for therapeutic
      applications, the product of energy density and number of pulses should not
      exceed a certain predetermined limit.

PMID- 26206822
TI  - Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles.
AB  - OBJECTIVES: A protocol was designed to produce albumin-coated microbubbles (MBs)
      loaded with functionalized polylactide (PLA) nanoparticles (NPs) for future drug
      delivery studies. METHODS: Microbubbles resulted from the sonication of 5% bovine
      serum albumin and 15% dextrose solution. Functionalized NPs were produced by
      mixing fluorescent PLA and PLA-polyethylene glycol-carboxylate conjugates.
      Nanoparticle-loaded MBs resulted from the covalent conjugation of functionalized
      NPs and MBs. Three NP/MB volume ratios (1/1, 1/10, and 1/100) and unloaded MBs
      were produced and compared. Statistical evaluations were based on quantitative
      analysis of 3 parameters at 4 time points (1, 4, 5, and 6 days post MB
      fabrication): MB diameter using a circle detection routine based on the Hough
      transform, MB number density using a hemocytometer, and NP-loading yield based on
      MB counts from fluorescence and light microscopic images. Loading capacity of the
      albumin-coated MBs was evaluated by fluorescence. RESULTS: Loaded MB sizes were
      stable over 6 days after production and were not significantly different from
      that of time-matched unloaded MBs. Number density evaluation showed that only 1/1
      NP/MB volume ratio and unloaded MB number densities were stable over time, and
      that the 1/1 MB number density evaluated at each time point was not significantly
      different from that of unloaded MBs. The 1/10 and 1/100 NP/MB volume ratios had
      unstable number densities that were significantly different from that of unloaded
      MBs (P < .05). Fluorescence evaluation suggested that 1/1 MBs had a higher NP
      loading yield than 1/10 and 1/100 MBs. Quantitative loading evaluation suggested
      that the 1/1 MBs had a loading capacity of 3700 NPs/MB. CONCLUSIONS: A protocol
      was developed to load albumin MBs with functionalized PLA NPs for further drug
      delivery studies. The 1/1 NP/MB volume ratio appeared to be the most efficient to
      produce stable loaded MBs with a loading capacity of 3700 NPs/MB.

PMID- 26206823
TI  - Quantitative Ultrasound Comparison of MAT and 4T1 Mammary Tumors in Mice and Rats
      Across Multiple Imaging Systems.
AB  - OBJECTIVES: Quantitative ultrasound estimates such as the frequency-dependent
      backscatter coefficient (BSC) have the potential to enhance noninvasive tissue
      characterization and to identify tumors better than traditional B-mode imaging.
      Thus, investigating system independence of BSC estimates from multiple imaging
      platforms is important for assessing their capabilities to detect tissue
      differences. METHODS: Mouse and rat mammary tumor models, 4T1 and MAT,
      respectively, were used in a comparative experiment using 3 imaging systems
      (Siemens, Ultrasonix, and VisualSonics) with 5 different transducers covering a
      range of ultrasonic frequencies. RESULTS: Functional analysis of variance of the
      MAT and 4T1 BSC-versus-frequency curves revealed statistically significant
      differences between the two tumor types. Variations also were found among results
      from different transducers, attributable to frequency range effects. At 3 to 8
      MHz, tumor BSC functions using different systems showed no differences between
      tumor type, but at 10 to 20 MHz, there were differences between 4T1 and MAT
      tumors. Fitting an average spline model to the combined BSC estimates (3-22 MHz)
      demonstrated that the BSC differences between tumors increased with increasing
      frequency, with the greatest separation above 15 MHz. Confining the analysis to
      larger tumors resulted in better discrimination over a wider bandwidth.
      CONCLUSIONS: Confining the comparison to higher ultrasonic frequencies or larger
      tumor sizes allowed for separation of BSC-versus-frequency curves from 4T1 and
      MAT tumors. These constraints ensure that a greater fraction of the backscattered
      signals originated from within the tumor, thus demonstrating that statistically
      significant tumor differences were detected.

PMID- 26206824
TI  - Comparisons of Positron Emission Tomography/Computed Tomography and Ultrasound
      Imaging for Detection of Internal Mammary Lymph Node Metastases in Patients With
      Breast Cancer and Pathologic Correlation by Ultrasound-Guided Biopsy Procedures.
AB  - OBJECTIVES: To compare the diagnostic performance of [(18)F]fluorodeoxyglucose
      positron emission tomography/computed tomography (PET/CT) and ultrasound imaging
      (US) with pathologic results obtained by US-guided biopsy and to evaluate the
      role of US in detecting internal mammary lymph node (LN) metastases in patients
      with breast cancer. METHODS: Between January 2008 and December 2012, 37 patients
      with breast cancer (median age, 51.4 years; range, 40-79 years) underwent US
      guided biopsy for suspected internal mammary LN metastases. Medical records,
      radiologic images, and reports were reviewed and correlated with pathologic
      results. RESULTS: The positive internal mammary LN metastasis rate was 78.4%. All
      biopsies were performed safely without major complications. Only 8.1% of obtained
      samples were unsatisfactory. There were statistically significant differences in
      lesion size (P = .0002), standardized uptake value on PET/CT (P = .0015), biopsy
      methods (P = .002), and specimen adequacy (P = .007) between metastatic and
      benign groups. Of the clinical factorsreviewed, only concurrent distant
      metastasis was correlated with internal mammary LN metastasis (P< .0001).
      Sensitivities for detecting internal mammary LN metastases were 76.7%, 96.7%, and
      92.9% for initial US examinations, initial US combined with second-look US for
      initially missed cases, and PET/CT, respectively (P= .017). In a subgroup
      analysis, the only significant difference found was in sensitivities between
      initial and combined US (P = .019). In a receiver operating characteristic curve
      analysis, the area under the curve for PET/CT using standardized uptake criteria
      (0.87) was higher than that for US using size criteria (0.83); however, this
      difference was not significant. CONCLUSIONS: Although PET/CT is the best
      noninvasive method for evaluating internal mammary LN metastases, US is also
      useful if internal mammary LN evaluation is routine during standard US
      surveillance of patients with breast cancer. Additionally, US-guided biopsies
      could be performed immediately on any suspected metastases and yield a high
      positive rate without serious complications.

PMID- 26206825
TI  - Assessment of Intracranial Structure Volumes in Fetuses With Growth Restriction
      by 3-Dimensional Sonography Using the Extended Imaging Virtual Organ Computer
      Aided Analysis Method.
AB  - OBJECTIVES: To assess intracranial structure volumes by 3-dimensional (3D)
      sonography in fetuses with growth restriction. METHODS: We conducted a
      prospective cross-sectional case-control study involving 59 fetuses with growth
      restriction (38 fetuses with estimated weight <3rd percentile and 21 fetuses with
      estimated weight between 3rd and 10th percentiles, according to Hadlock et al
      [Radiology 1984; 150:535-540]) and 54 controls between 24 and 34 weeks'
      gestation. The following fetal intracranial structure volumes were assessed:
      cerebellum, brain, and frontal region. The volume was assessed by 3D sonography
      using the extended imaging virtual organ computer-aided analysis method with 10
      sequential planes. Analysis of variance was used to compare fetal groups. The
      intraclass correlation coefficient was used to assess intraobserver and
      interobserver reproducibility. RESULTS: Statistical significance between the
      brain, frontal region, and cerebellar volumes and a relationship between the
      frontal region and the brain in fetuses with estimated weights below the 3rd
      percentile and controls were observed (P < .001; P < .001; and P = .002; and P =
      .008, respectively). Good intraobserver and interobserver reproducibility was
      observed for the fetal brain, frontal region, and cerebellar volumes, with
      intraclass correlation coefficients of 0.998, 0.997, 0.997, 0.999, 0.997, and
      0.998, respectively. CONCLUSIONS: The intracranial structure volumes assessed by
      3D sonography using the extended imaging virtual organ computer-aided analysis
      method were reduced in fetuses with growth restriction (estimated weight <3rd
      percentile).

PMID- 26206826
TI  - Transabdominal Sonographic Study of the Cavum Vergae Detection Rate in Healthy
      Third-Trimester Fetuses.
AB  - OBJECTIVES: We aimed to measure the thickness and volume of the cavum vergae by
      sonography in fetuses at gestational ages of 25 to 41 weeks to determine the
      relationship of cavum vergae thickness and volume with gestational age and
      biparietal diameter and to estimate the rate of cavum vergae closure in relation
      to gestational age. METHODS: A total of 336 patients in their third trimester of
      pregnancy had transabdominal sonography. The fetal cavum vergae was scanned in
      the coronal and axial planes. The thickness of the anteroposterior diameter of
      the cavum vergae and the largest inner surface were measured after marking the
      internal borders of the structure, and then longitudinal and vertical sizes were
      obtained. The values obtained were multiplied by each other and then by 0.52 to
      obtain the cavum vergae volume. RESULTS: In 55 of 322 cases, the cavum vergae
      volume and thickness could not be calculated because the cavum vergae was closed.
      In the remaining cases, the cavum vergae volume and thickness and biparietal
      diameter were measured. Although the degree of correlation between cavum vergae
      thickness and volume increased with increasing gestational age, there was no
      correlation between cavum vergae thickness and volume at 37 to 41 weeks. There
      was a positive but weak statistically significant correlation between biparietal
      diameter and cavum vergae volume (P= .05), but there was no statistically
      significant correlation between biparietal diameter and cavum vergae thickness.
      The cavum vergae closure rate increased significantly as gestational age
      increased (P < .001). CONCLUSIONS: Cavum vergae closure increases as gestational
      age increases. However, we did not find any relationships between cavum vergae
      thickness and volume, gestational age, and biparietal diameter.

PMID- 26206827
TI  - Utility of a Single 3-Vessel View in the Evaluation of the Ventricular Outflow
      Tracts.
AB  - OBJECTIVES: Prenatal diagnosis of congenital heart disease can improve neonatal
      outcomes. The purpose of this study was to evaluate the utility of an isolated 3
      vessel view image in evaluating the ventricular outflow tracts. METHODS: Three
      vessel view images were prospectively collected from consecutive patients
      referred to a regional fetal heart center for fetal echocardiography between
      gestational ages of 18 weeks and 23 weeks 6 days. Cardiac malformations were
      categorized as anomalies of the outflow tracts, the 4-chamber view, or combined
      lesions. A single representative still-frame 3-vessel view image was reviewed by
      2 independent and blinded observers who were asked to label each image as
      "normal" or "abnormal." Test characteristics of the isolated 3-vessel view were
      calculated. RESULTS: During the study period, 122 consecutive patients (139
      fetuses) underwent fetal echocardiography. Eight fetuses with fetal chest
      anomalies and 12 fetuses with oblique images were excluded. Thirty-four of 119
      fetuses (28.6%) had abnormal echocardiograms, including 11 outflow tract
      anomalies and 16 combined anomalies. Using the 3-vessel view alone, both
      reviewers achieved 91% sensitivity for the detection of isolated outflow tract
      anomalies and mean sensitivity of 88% for combined anomalies. All cases of
      tetralogy of Fallot and transposition of the great arteries were identified in
      the 3-vessel view. CONCLUSIONS: A single 3-vessel view image can serve as a
      representative view of the outflow tracts and can show ventricular outflow tract
      anomalies with high sensitivity. Given that the conventional outflow tract views
      can be difficult to obtain, the 3-vessel view may serve as an effective first
      line view when evaluating the ventricular outflow tracts for congenital heart
      disease.

PMID- 26206828
TI  - Use of the Combined First-Trimester Screen in High- and Low-Risk Patient
      Populations After Introduction of Noninvasive Prenatal Testing.
AB  - OBJECTIVES: To report changes in the use of the combined first-trimester screen
      (FTS) in patients classified as high and low risk for fetal aneuploidy, including
      after introduction of noninvasive prenatal testing (NIPT). METHODS: A
      prospectively collected database was reviewed to investigate changes in FTS use
      before and after American College of Obstetricians and Gynecologists (ACOG)
      Practice Bulletin No. 77 (Obstet Gynecol 2007; 109:217-227), which recommended
      that all patients be offered aneuploidy screening, and after NIPT introduction.
      High-risk patients were classified as 35 years or older at the estimated time of
      delivery or those with an abnormal prior screen, abnormal ultrasound findings, or
      family history of aneuploidy. Data were normalized per 100 morphologic ultrasound
      examinations to account for changes in patient number over time. Statistical
      significance was defined as P < .05. RESULTS: A total of 10,125 FTSs were
      recorded during the 88-month study period, including 2962 in high-risk patients
      and 7163 in low-risk patients. The total number of FTSs performed per 100
      morphologic ultrasound examinations significantly increased after ACOG Practice
      Bulletin No. 77 and significantly decreased after NIPT introduction. In high-risk
      patients, the total number of FTSs performed per 100 morphologic ultrasound
      examinations significantly increased after ACOG Practice Bulletin No. 77 but
      significantly decreased after NIPT introduction. In contrast, in low-risk
      patients, the total number of FTSs performed per 100 morphologic ultrasound
      examinations significantly increased after ACOG Practice Bulletin No.77 but was
      not statistically different after NIPT introduction. CONCLUSIONS: American
      College of Obstetricians and Gynecologists Practice Bulletin No. 77 significantly
      increased patient use of FTS. The introduction of NIPT significantly decreased
      FTS use in the high-risk population but not in the low-risk population.

PMID- 26206829
TI  - Focused Assessment With Sonography for Trauma Examination: Reexamining the
      Importance of the Left Upper Quadrant View.
AB  - OBJECTIVES: The purpose of this study was to determine the frequency and
      predominant location of isolated free fluid in the left upper quadrant (LUQ) on
      focused assessment with sonography for trauma (FAST) examinations of adult
      patients with trauma presenting to the emergency department. METHODS: We
      conducted a retrospective review of adult patients with positive FAST results for
      free fluid in the abdomen at 2 academic emergency departments. Eligible FAST
      examinations were reviewed for the presence of fluid in the LUQ and exact
      location of free fluid within the LUQ. RESULTS: A total of 100 FAST examinations
      with free fluid in the abdomen that met inclusion criteria were identified during
      the study period. Overall 32 of 100 (32%; 95% confidence interval [CI], 23.5%
      41.6%) of patients with positive FAST results were found to have free fluid in
      the LUQ. Only 6 of 100 (6%; 95% CI, 2.5%-11.9%) patients with positive FAST
      results had free fluid isolated to the LUQ. Of these 6 patients with isolated LUQ
      free fluid, none had free fluid isolated to the splenorenal fossa alone; 1 had
      free fluid isolated to the subphrenic space (above the spleen/below the
      diaphragm); and 4 had free fluid visible only in the left paracolic
      gutter/inferior to the spleen. Twenty-seven of 32 patients (84%; 95% CI, 69.1%
      93.8%) with free fluid anywhere in the LUQ were also found to have fluid in the
      left paracolic gutter. CONCLUSIONS: Free fluid isolated to the LUQ occurs in a
      clinically significant number of adult patients with trauma and positive FAST
      results. Isolated fluid accumulation was often seen within the left paracolic
      gutter.

PMID- 26206830
TI  - Head and Neck Ultrasound Education-A Multimodal Educational Approach in the
      Predoctoral Setting: A Pilot Study.
AB  - OBJECTIVES: With the increased implementation of ultrasound in medical education,
      it is important to continually improve instructional methods. In this study, we
      demonstrate that by augmenting the traditional methods of instructor
      demonstration and student practice on a healthy volunteer with additional
      modalities, such as didactic presentation, simulated pathologic cases, and
      simulated procedures, students gain a more comprehensive understanding of and
      confidence in ultrasound technique and pathology. METHODS: A multimodal
      curriculum was developed and applied to head and neck ultrasound sessions of our
      institution's Ultrasound Symposium. Participants were asked to fill out surveys
      rating each instructional modality as well as preinstructional and
      postinstructional confidence. The survey results were divided into a group of
      first- and second-year medical students who had previous ultrasound training and
      a group of third- and fourth-year students who were ultrasound "naive." RESULTS:
      The survey showed that the first- and second-year student group (n = 8) had an
      average preinstructional confidence of 4.14/10 compared to 1.44/10 in the third-
      and fourth-year student group (n = 9) (P = .003). Following the instructional
      sessions, the students' confidence increased respectively to 8.14/10 and 7.78/10
      (P= .53), showing a 4.00 (96%) increase in the first- and second-year group and a
      6.34 (440%) increase in the third- and fourth-year group. The combined results of
      all student teaching modality ratings showed that instructor demonstration was
      rated the highest (9.47) and computerized simulation lowest (8.25). CONCLUSIONS:
      Overall, our study shows that multimodal ultrasound instruction was beneficial in
      increasing both ultrasound-trained and ultrasound-naive medical students'
      confidence in head and neck ultrasound.

PMID- 26206831
TI  - Musculoskeletal Sonography for Evaluation of Anatomic Variations of Extensor
      Tendon Synovial Sheaths in the Wrist.
AB  - OBJECTIVES: The purpose of this article is to show the anatomic variations of
      extensor tendon synovial sheaths in the wrist. METHODS: Videos from 157 patients
      that were available in the electronic database were reviewed. Sonography showed
      involvement of 186 tendon sheaths. RESULTS: We describe our center's experience
      with most tendon variants described in the literature and show the sonographic
      appearance of the most frequent ones. CONCLUSIONS: Sonography is an accepted,
      safe, and efficient method for evaluating conditions characterized by effusion
      into the synovial sheaths of the wrist extensor tendons. Knowledge of anatomy and
      anatomic abnormalities of these sheaths is essential for diagnosis and for
      correct ultrasound-guided injection therapy or, less frequently, planning a
      surgical approach.

PMID- 26206832
TI  - Ultrasound-Guided Intratendinous Injections With Platelet-Rich Plasma or
      Autologous Whole Blood for Treatment of Proximal Hamstring Tendinopathy: A Double
      Blind Randomized Controlled Trial.
AB  - OBJECTIVES: To compare the effects of ultrasound-guided platelet-rich plasma
      (PRP) and whole blood (WB) injections in patients with chronic hamstring
      tendinopathy. METHODS: In a prospective double-blind randomized controlled trial,
      PRP or WB was injected under ultrasound guidance into the proximal hamstring
      tendon in a cohort of patients with clinically suspected hamstring tendinosis.
      Questionnaires were administered before injection and 2, 6, and 12 weeks and 6
      months after injection. Pain and function outcomes were measured via the Modified
      Harris Hip Score (MHHS), Hip Outcome Scores for activities of daily living (ADL)
      and sport-specific function, and International Hip Outcome Tool 33 (IHOT-33).
      Diagnostic ultrasound was used to compare preinjection and 6-month postinjection
      tendon appearances. RESULTS: The WB group showed greater improvements in pain and
      function over the PRP group before 12 weeks, whereas the PRP group showed
      improved outcomes over WB at 6 months. None of these between-group outcome
      measures, except 6-week IHOT-33, showed statistical significance. Comparing
      preinjection and 6-month scores, the PRP group showed significant improvements in
      ADL (P = .018) and IHOT-33 (P = .28) scores, whereas the WB group showed no
      significant improvements from baseline. The WB group showed significantly
      decreased pain with 15-minute sitting (P= .008) at 6 months. Ultrasound imaging
      showed no significant differences between PRP and WB group tendon appearances.
      CONCLUSIONS: Both PRP and WB groups showed improvements in all outcome measures
      at 6 months. The PRP group showed significant improvements in 6-month ADL and
      IHOT-33 scores. The WB group reached significance in 15-minute sitting pain. No
      significant between-group differences were observed at any time point.

PMID- 26206833
TI  - Sonographic Features of Superficial-Type Nodular Fasciitis in the Musculoskeletal
      System.
AB  - OBJECTIVES: We evaluated the sonographic features of superficial-type nodular
      fasciitis in 9 pathologically proven cases. METHODS: Review of the radiology and
      pathology databases yielded 14 cases of histologically proven superficial-type
      nodular fasciitis, which was defined as nodular fasciitis located in the
      subcutaneous fat layer or outer muscle fascia between the subcutaneous fat layer
      and muscle. Sonograms were available in 9 patients. Two musculoskeletal
      radiologists retrospectively reviewed all cases in consensus. Imaging features
      evaluated included the fasciitis location in the body, size, relationship with
      the fascia, echogenicity, vascularity, and location of the center. RESULTS: There
      were 4 male and 5 female patients. The mean age was 35 years (range, 8-49 years).
      The masses ranged in size from 0.8 to 2 cm, with 90% measuring less than 1.8 cm.
      Five masses developed in the forearm (4 cases) or elbow (1 case). Six masses were
      located in the subcutaneous fat layer, and 3 masses were in the fascia. Seven
      masses were in direct contact with the outer muscle fascia, whereas 2 masses were
      indistinctly in contact with the fascia. These masses showed a hypoechoic
      background with echogenic foci or peripheral hyperechoic nodules. In all 3 of the
      masses within the fascia, the findings were similar to those of neurogenic
      tumors. The vascularity of the masses was variable, but most (7 of 9 cases)
      showed no substantial vascularity. All masses had centers of less than half the
      thickness of the subcutaneous fat layer. CONCLUSIONS: Superficial-type nodular
      fasciitis is often located in the deep subcutaneous fat near the muscle fascia,
      has a hypoechoic appearance with echogenic foci or peripheral hyperechoic
      nodules, and quite often does not show internal vascular flow. If a superficial
      soft tissue mass has the above findings, superficial-type nodular fasciitis
      should be included in the differential diagnosis.

PMID- 26206834
TI  - Creation of a High-fidelity, Low-cost Pediatric Skull Fracture Ultrasound
      Phantom.
AB  - Over the past decade, point-of-care ultrasound has become a common tool used for
      both procedures and diagnosis. Developing high-fidelity phantoms is critical for
      training in new and novel point-of-care ultrasound applications. Detecting skull
      fractures on ultrasound imaging in the younger-than-2-year-old patient is an
      emerging area of point-of-care ultrasound research. Identifying a skull fracture
      on ultrasound imaging in this age group requires knowledge of the appearance and
      location of sutures to distinguish them from fractures. There are currently no
      commercially available pediatric skull fracture models. We outline a novel
      approach to building a cost-effective, simple, high-fidelity pediatric skull
      fracture phantom to meet a unique training requirement. 

PMID- 26206835
TI  - A Cost-effective, Gelatin-Based Phantom Model for Learning Ultrasound-Guided Fine
      Needle Aspiration Procedures of the Head and Neck.
AB  - The rise in popularity of ultrasound imaging has seen a corresponding increase in
      demand for effective training tools such as phantom models. They are especially
      useful for teaching and practice of invasive procedures, such as fine-needle
      aspiration of lesions of the head and neck. We have created 2 gelatin models out
      of inexpensive, commonly available materials that can be used in sequence to
      learn head and neck fine-needle aspiration. Fundamental skills can be learned
      first on the flat, rectangular model, whereas the second, cylindrical model more
      closely represents human anatomy and can be used to develop more advanced
      technique. 

PMID- 26206836
TI  - Sonographic Findings of Subcutaneous Sarcoidosis in 3 Cases.
AB  - Subcutaneous sarcoidosis occurs infrequently among cases of cutaneous
      sarcoidosis. To our knowledge, few studies have described the sonographic
      characteristics of subcutaneous sarcoidosis. Here we report the sonographic
      characteristics of 3 cases of this condition. Our results revealed 4 features:
      (1) an irregular hypoechoic appearance, (2) heterogeneous echogenicity, (3)
      perilesional hyperechoic changes, and (4) abnormal Doppler signals. Sonography is
      a rapid, simple, and noninvasive procedure that is useful for initial evaluation
      of granulomatous lesions such as subcutaneous sarcoidosis. 

PMID- 26206837
TI  - Contrast-Enhanced Sonography for Monitoring Neoadjuvant Chemotherapy in Soft
      Tissue Sarcomas.
AB  - Neoadjuvant chemotherapy is a mainstay in treating soft tissue sarcomas. Soft
      tissue sarcomas can show an increase in size and central necrosis, with a
      decrease in the viable tumor, as an initial response to neoadjuvant chemotherapy.
      Thus, the maximum tumor diameter may not reliably assess the response to this
      therapy. Contrast-enhanced sonography may address this limitation. We evaluated 4
      patients with soft tissue sarcomas by contrast-enhanced sonography, performed
      concomitantly with conventional imaging (computed tomography, magnetic resonance
      imaging, or positron emission tomography). Quantitative analysis was also
      performed on 1 sarcoma. A viable, enhancing tumor versus tumor necrosis was
      nearly identical on contrast-enhanced sonography and conventional imaging.
      Preliminary results demonstrate potential for contrast-enhanced sonographic
      monitoring of soft tissue sarcomas during neoadjuvant chemotherapy. 

PMID- 26206838
TI  - In Utero Diagnosis of Unilateral Bronchial Atresia: One Pathologically Proven and
      2 Presumed Cases With Similar Sonographic Findings at Presentation.
AB  - Unilateral bronchial atresia is a rare prenatal diagnosis that can be confused
      with other congenital lung abnormalities, particularly congenital pulmonary
      airway malformation. Accurate distinction between these entities is important for
      appropriate clinical care and prognosis. Familiarity of the key imaging and
      clinical features of unilateral bronchial atresia in comparison to other fetal
      lung abnormalities should increase the likelihood of achieving a timely and
      accurate diagnosis. 

PMID- 26206839
TI  - Sonographic Findings in Fetal Renal Vein Thrombosis.
AB  - We present the sonographic findings of fetal renal vein thrombosis in a series of
      6 patients. The mean gestational age at diagnosis was 31.2 weeks. Four cases were
      unilateral, and 2 were bilateral. The most common findings were renal enlargement
      and intrarenal vascular calcifications, followed by increased renal parenchymal
      echogenicity. Inferior vena cava thrombosis was found in 4 patients and common
      iliac vein thrombosis in 2. Fetal renal vein thrombosis is an uncommon diagnosis
      with characteristic sonographic findings. The presence of these findings should
      prompt Doppler interrogation of the renal vein and inferior vena cava to confirm
      the diagnosis. 

PMID- 26206840
TI  - Perivascular Epithelioid Cell Tumor Masquerading as Retained Placenta.

PMID- 26206841
TI  - Prenatal Diagnosis of Anatomically Corrected Malposition of the Great Arteries.

PMID- 26206842
TI  - Suspected Renal Cysts: Don't Forget Color Doppler Sonography.

PMID- 26206843
TI  - Pneumomediastinum as a Sonographic Mimic of Pneumothorax.

PMID- 26206844
TI  - New Parameters for Evaluating Peripheral Nerve Disorders on Sonography and
      Magnetic Resonance Imaging.

PMID- 26206845
TI  - Cuticle Affects Calculations of Internal CO2 in Leaves Closing Their Stomata.
AB  - Analyzing the assimilation rate (A) relative to the CO(2) concentration inside
      leaves (C(i)) has been a useful approach for investigating plant responses to
      various environments. Nevertheless, there are uncertainties in calculating C(i)
      when stomata close, restricting the application. Here, A-C(i) curves were traced
      in sunflower (Helianthus annuus L.) leaves using a method for directly measuring
      C(i). The method was incorporated into an LI-6400 open gas exchange system, and
      stomata were closed by feeding 10 uM ABA through petioles. The conductance to
      CO(2) was derived from the directly measured C(i) and compared with the
      conductance from the water vapor flux (i.e. the standard calculation). When
      stomata were open, measured and calculated C(i) gave similar A-C(i) curves. When
      stomata were closed, the curves differed because measured C(i) departed from the
      calculated value. This difference caused the calculation to trace an artifactual
      limitation of photosynthesis. The direct measurement avoided this problem and
      followed the curve for leaves with open stomata. Largely because of the cuticle,
      the calculation overestimated CO(2) entry into the leaf because the cuticle
      transmitted more water vapor than CO(2), and the calculation relied on water
      vapor. Consequently, the standard calculation gave conductances larger than those
      from directly measured C(i). Although the cuticle conductance to water vapor
      remained constant as stomata closed, it increasingly contributed to the
      overestimation of C(i). The system provided here is not affected by these cuticle
      properties and thus is expected to open up the opportunity for A-C(i) analysis in
      plant physiology.

PMID- 26206846
TI  - Editorial Commentary: Genomic Epidemiology: Revealing Hidden Reservoirs for
      Klebsiella pneumoniae.

PMID- 26206848
TI  - Atrial fibrillation and exercise in women: some answers given, some questions
      remain.

PMID- 26206847
TI  - Intermingled Klebsiella pneumoniae Populations Between Retail Meats and Human
      Urinary Tract Infections.
AB  - BACKGROUND: Klebsiella pneumoniae is a common colonizer of the gastrointestinal
      tract of humans, companion animals, and livestock. To better understand potential
      contributions of foodborne K. pneumoniae to human clinical infections, we
      compared K. pneumoniae isolates from retail meat products and human clinical
      specimens to assess their similarity based on antibiotic resistance, genetic
      relatedness, and virulence. METHODS: Klebsiella pneumoniae was isolated from
      retail meats from Flagstaff grocery stores in 2012 and from urine and blood
      specimens from Flagstaff Medical Center in 2011-2012. Isolates underwent
      antibiotic susceptibility testing and whole-genome sequencing. Genetic
      relatedness of the isolates was assessed using multilocus sequence typing and
      phylogenetic analyses. Extraintestinal virulence of several closely related meat
      source and urine isolates was assessed using a murine sepsis model. RESULTS: Meat
      source isolates were significantly more likely to be multidrug resistant and
      resistant to tetracycline and gentamicin than clinical isolates. Four sequence
      types occurred among both meat-source and clinical isolates. Phylogenetic
      analyses confirmed close relationships among meat-source and clinical isolates.
      Isolates from both sources showed similar virulence in the mouse sepsis model.
      CONCLUSIONS: Meat-source K. pneumoniae isolates were more likely than clinical
      isolates to be antibiotic resistant, which could reflect selective pressures from
      antibiotic use in food-animal production. The close genetic relatedness of meat
      source and clinical isolates, coupled with similarities in virulence, suggest
      that the barriers to transmission between these 2 sources are low. Taken
      together, our results suggest that retail meat is a potential vehicle for
      transmitting virulent, antibiotic-resistant K. pneumoniae from food animals to
      humans.

PMID- 26206849
TI  - Exercise, sex and atrial fibrillation: arrhythmogenesis beyond Y-chromosome?

PMID- 26206850
TI  - Techniques and Outcomes for the Treatment of Paravalvular Leak.

PMID- 26206851
TI  - Management of mixed arterial venous lower extremity ulceration: A review.
AB  - Mixed arterial venous disease is estimated to affect up to 26% of patients with
      lower extremity ulcerations. However, its clinical significance and
      pathophysiology are incompletely understood. Furthermore, there is no consensus
      on the optimal treatment modality, whether conservative or operative. In this
      review paper, we describe the current understanding of the pathophysiology of
      mixed arterial venous lower extremity ulcers. Guidelines for diagnostic tests for
      patients with mixed arterial venous diseases are discussed. We review some of the
      newer biological skin substitutes for conservative wound care. Finally, we
      propose a treatment algorithm based on current available data. 

PMID- 26206853
TI  - The Effects of Workload and Working Conditions on Operating Room Nurses and
      Technicians.
AB  - This study was conducted between August 15 and September 20, 2013, to determine
      the effects of workload and working conditions on operating room (OR) nurses and
      technicians. The study sample included 74 OR nurses and technicians working in a
      private university's six hospitals. The Individual Workload Perception Scale and
      a questionnaire that collected data on risk and environmental factors were used.
      The mean age of study participants was 29.3 +/- 6.7 years, and 62.2% of the
      participants were female. More than 90% of the nurses and technicians had
      experienced spills or splashing of blood or other body fluids; anesthetic gases
      and radiation had affected 63.5% and 71.6% of nurses and technicians,
      respectively; 63.5% reported lumbar pain; and 46.6% defined the work environment
      as very stressful. The average workload scale score was 32.4 +/- 6.2 (min = 11,
      max = 55). OR nurses and technicians are exposed to many occupational risks. 

PMID- 26206852
TI  - Pseudomonas syringae Effector Avirulence Protein E Localizes to the Host Plasma
      Membrane and Down-Regulates the Expression of the NONRACE-SPECIFIC DISEASE
      RESISTANCE1/HARPIN-INDUCED1-LIKE13 Gene Required for Antibacterial Immunity in
      Arabidopsis.
AB  - Many bacterial pathogens of plants and animals deliver effector proteins into
      host cells to promote infection. Elucidation of how pathogen effector proteins
      function not only is critical for understanding bacterial pathogenesis but also
      provides a useful tool in discovering the functions of host genes. In this study,
      we characterized the Pseudomonas syringae pv tomato DC3000 effector protein
      Avirulence Protein E (AvrE), the founding member of a widely distributed, yet
      functionally enigmatic, bacterial effector family. We show that AvrE is localized
      in the plasma membrane (PM) and PM-associated vesicle-like structures in the
      plant cell. AvrE contains two physically interacting domains, and the amino
      terminal portion contains a PM-localization signal. Genome-wide microarray
      analysis indicates that AvrE, as well as the functionally redundant effector
      Hypersensitive response and pathogenicity-dependent Outer Protein M1, down
      regulates the expression of the NONRACE-SPECIFIC DISEASE RESISTANCE1/HARPIN
      INDUCED1-LIKE13 (NHL13) gene in Arabidopsis (Arabidopsis thaliana). Mutational
      analysis shows that NHL13 is required for plant immunity, as the nhl13 mutant
      plant displayed enhanced disease susceptibility. Our results defined the action
      site of one of the most important bacterial virulence proteins in plants and the
      antibacterial immunity function of the NHL13 gene. 

PMID- 26206854
TI  - Extracorporeal Membrane Oxygenation as a Bridge to Pediatric Heart
      Transplantation: Effect on Post-Listing and Post-Transplantation Outcomes.
AB  - BACKGROUND: Current organ allocation algorithms direct hearts to the sickest
      recipients to mitigate death while waiting. This may result in lower post
      transplant (Tx) survival for high-risk candidates mandating close examination to
      determine the appropriateness of different technologies as a bridge to Tx.
      METHODS AND RESULTS: We analyzed all patients (<18 years old) from the Pediatric
      Heart Transplant Study (PHTS) database listed for heart Tx (1993-2013) to
      determine the effect of extracorporeal membrane oxygenation (ECMO) support at the
      time of listing and the time of Tx on waitlist mortality and post-Tx outcomes.
      Eight percent of patients were listed on ECMO, and within 12 months, 49% had
      undergone Tx, 35% were deceased, and 16% were alive waiting. Survival at 12
      months after listing (censored at Tx) was worse in patients on ECMO at listing
      (50%) compared with ventricular assist device at listing (76%) or not on ECMO or
      ventricular assist device at listing (76%; P<0.0001). Two hundred three (5%)
      patients underwent Tx from ECMO; 135 (67%) had been on ECMO since listing, and 67
      (33%) had deteriorated to ECMO support while waiting. Survival after Tx was worse
      in patients who underwent Tx from ECMO (3 years: 64%) versus on ventricular
      assist device at Tx (3 years: 84%) or not on ECMO/ventricular assist device at Tx
      (3 years: 85%; P<0.0001). Patients transplanted from ECMO at age <1 year had the
      worst survival. CONCLUSIONS: Pediatric patients requiring ECMO support before
      heart Tx have poor outcomes. Prioritization of donor hearts to children
      waitlisted on ECMO warrants careful consideration because of ECMO's high pre- and
      post-Tx mortality.

PMID- 26206855
TI  - Prevalence and Impact of Chagas Disease Among Latin American Immigrants With
      Nonischemic Cardiomyopathy in Los Angeles, California.
AB  - BACKGROUND: Chagas disease is a well-known cause of cardiomyopathy in Latin
      America; however, 300 000 individuals are estimated to have Chagas disease in the
      United States. This study examined the prevalence and impact of Chagas
      cardiomyopathy (CCM) in a US population. We hypothesized that patients with CCM
      would have increased morbidity and mortality when compared with patients with non
      CCM. METHODS AND RESULTS: This is a single-center, prospective cohort study.
      Enrollment criteria were new diagnosis of nonischemic cardiomyopathy (left
      ventricular ejection fraction <=40%) and previous residence in Latin America for
      at least 12 months. Serological testing for Trypanosoma cruzi was performed at
      enrollment. The primary end point was all-cause mortality or heart
      transplantation. The secondary end point was heart failure-related
      hospitalization. A total of 135 patients were enrolled, with a median of 43
      months of follow-up. Chagas disease was diagnosed in 25 (19%) patients. The
      primary end point occurred in 9 patients (36%) in the CCM group and in 11
      patients (10%) in the non-CCM group (hazard ratio [HR], 4.46; 95% confidence
      interval, 1.8-10.8; P=0.001). The secondary end point occurred in 13 patients
      (52%) in the CCM group and in 35 patients (32%) in the non-CCM group (HR, 2.22;
      95% confidence interval, 1.2-4.2; P=0.01). CONCLUSIONS: There is a high
      prevalence of Chagas disease among Latin American immigrants diagnosed with
      nonischemic cardiomyopathy in Los Angeles. Advanced CCM portends a poor prognosis
      and is associated with increased all-cause mortality/heart transplantation and
      heart failure-related hospitalization.

PMID- 26206856
TI  - Rhesus rotavirus VP4 sequence-specific activation of mononuclear cells is
      associated with cholangiopathy in murine biliary atresia.
AB  - Biliary atresia (BA), a neonatal obstructive cholangiopathy, remains the most
      common indication for pediatric liver transplantation in the United States. In
      the murine model of BA, Rhesus rotavirus (RRV) VP4 surface protein determines
      biliary duct tropism. In this study, we investigated how VP4 governs induction of
      murine BA. Newborn mice were injected with 16 strains of rotavirus and observed
      for clinical symptoms of BA and mortality. Cholangiograms were performed to
      confirm bile duct obstruction. Livers and bile ducts were harvested 7 days
      postinfection for virus titers and histology. Flow cytometry assessed mononuclear
      cell activation in harvested cell populations from the liver. Cytotoxic NK cell
      activity was determined by the ability of NK cells to kill noninfected
      cholangiocytes. Of the 16 strains investigated, the 6 with the highest homology
      to the RRV VP4 (>87%) were capable of infecting bile ducts in vivo. Although the
      strain Ro1845 replicated to a titer similar to RRV in vivo, it caused no symptoms
      or mortality. A Ro1845 reassortant containing the RRV VP4 induced all BA
      symptoms, with a mortality rate of 89%. Flow cytometry revealed that NK cell
      activation was significantly increased in the disease-inducing strains and these
      NK cells demonstrated a significantly higher percentage of cytotoxicity against
      noninfected cholangiocytes. Rotavirus strains with >87% homology to RRV's VP4
      were capable of infecting murine bile ducts in vivo. Development of murine BA was
      mediated by RRV VP4-specific activation of mononuclear cells, independent of
      viral titers. 

PMID- 26206857
TI  - Neuropeptide S inhibits gastrointestinal motility and increases mucosal
      permeability through nitric oxide.
AB  - Neuropeptide S (NPS) receptor (NPSR1) polymorphisms are associated with enteral
      dysmotility and inflammatory bowel disease (IBD). This study investigated the
      role of NPS in conjunction with nitrergic mechanisms in the regulation of
      intestinal motility and mucosal permeability. In rats, small intestinal
      myoelectric activity and luminal pressure changes in small intestine and colon,
      along with duodenal permeability, were studied. In human intestine, NPS and NPSR1
      were localized by immunostaining. Pre- and postprandial plasma NPS was measured
      by ELISA in healthy and active IBD humans. Effects and mechanisms of NPS were
      studied in human intestinal muscle strips. In rats, NPS 100-4,000 pmol.kg(
      1).min(-1) had effects on the small intestine and colon. Low doses of NPS
      increased myoelectric spiking (P < 0.05). Higher doses reduced spiking and
      prolonged the cycle length of the migrating myoelectric complex, reduced
      intraluminal pressures (P < 0.05-0.01), and increased permeability (P < 0.01)
      through NO-dependent mechanisms. In human intestine, NPS localized at myenteric
      nerve cell bodies and fibers. NPSR1 was confined to nerve cell bodies.
      Circulating NPS in humans was tenfold below the ~0.3 nmol/l dissociation constant
      (Kd) of NPSR1, with no difference between healthy and IBD subjects. In human
      intestinal muscle strips precontracted by bethanechol, NPS 1-1,000 nmol/l induced
      NO-dependent muscle relaxation (P < 0.05) that was sensitive also to tetrodotoxin
      (P < 0.01). In conclusion, NPS inhibits motility and increases permeability in
      neurocrine fashion acting through NO in the myenteric plexus in rats and humans.
      Aberrant signaling and upregulation of NPSR1 could potentially exacerbate
      dysmotility and hyperpermeability by local mechanisms in gastrointestinal
      functional and inflammatory reactions. 

PMID- 26206858
TI  - Blocking peripheral serotonin synthesis by telotristat etiprate (LX1032/LX1606)
      reduces severity of both chemical- and infection-induced intestinal inflammation.
AB  - Mucosal inflammation is accompanied by an alteration in 5-HT. Intestinal 5-HT
      synthesis is catalyzed by tryptophan hydroxylase 1 (Tph1) and we have shown that
      mice deficient in this rate-limiting enzyme have reduced severity of intestinal
      inflammation in models of chemical-induced experimental colitis. Here, we
      investigated the effect of blocking peripheral 5-HT synthesis in generation of
      intestinal inflammation by a using peripheral Tph inhibitor, telotristat etiprate
      (LX1606), in models of intestinal inflammation. LX1606 was given orally either
      prophylactically or therapeutically to mice with dextran sulfate sodium (DSS)
      induced colitis or with infection with Trichuris muris. Severity of intestinal
      inflammation was measured by assessment of disease activity scores, histological
      damage, and MPO and inflammatory cytokine levels. LX1606 significantly reduced
      intestinal 5-HT levels and delayed onset and severity of DSS-induced acute and
      chronic colitis. This was associated with decreased MPO and proinflammatory
      cytokine levels compared with vehicle-treated controls. In the infection-induced
      inflammation model, treatment with LX1606 enhanced worm expulsion as well as
      increased IL-10 production and goblet cell numbers. LX1606-treated mice had
      significantly lower MPO and IL-1beta levels compared with controls postinfection.
      Our results demonstrate that peripheral 5-HT plays an important role in
      intestinal inflammation and in the generation of immune responses.
      Pharmacological reduction of peripheral 5-HT may serve as a potential strategy
      for modulating various intestinal inflammatory disorders. 

PMID- 26206859
TI  - The pH-sensing receptor OGR1 improves barrier function of epithelial cells and
      inhibits migration in an acidic environment.
AB  - The pH-sensing receptor ovarian cancer G protein-coupled receptor 1 (OGR1; GPR68)
      is expressed in the gut. Inflammatory bowel disease is typically associated with
      a decrease in local pH, which may lead to altered epithelial barrier function and
      subsequent gastrointestinal repair involving epithelial cell adhesion and
      migration. As the mechanisms underlying the response to pH changes are not well
      understood, we have investigated OGR1-mediated, pH-dependent signaling pathways
      in intestinal epithelial cells. Caco-2 cells stably overexpressing OGR1 were
      created and validated as tools to study OGR1 signaling. Barrier function,
      migration, and proliferation were measured using electric cell-substrate
      impedance-sensing technology. Localization of the tight junction proteins zonula
      occludens protein 1 and occludin and the rearrangement of cytoskeletal actin were
      examined by confocal microscopy. Paracellular permeability and protein and gene
      expression analysis using DNA microarrays were performed on filter-grown Caco-2
      monolayers. We report that an acidic pH shift from pH 7.8 to 6.6 improved barrier
      function and stimulated reorganization of filamentous actin with prominent basal
      stress fiber formation. Cell migration and proliferation during in vitro wound
      healing were inhibited. Gene expression analysis revealed significant
      upregulation of genes related to cytoskeleton remodeling, cell adhesion, and
      growth factor signaling. We conclude that acidic extracellular pH can have a
      signaling function and impact the physiology of intestinal epithelial cells. The
      deconstruction of OGR1-dependent signaling may aid our understanding of mucosal
      inflammation mechanisms. 

PMID- 26206860
TI  - Cortical folding and the potential for prognostic neuroimaging in schizophrenia.
AB  - In 41 patients with schizophrenia, we used neuroanatomical information derived
      from structural imaging to identify patients with more severe illness,
      characterised by high symptom burden, low processing speed, high degree of
      illness persistence and lower social and occupational functional capacity.
      Cortical folding, but not thickness or volume, showed a high discriminatory
      ability in correctly identifying patients with more severe illness. 

PMID- 26206862
TI  - Sleep problems and self-harm in adolescence.
AB  - BACKGROUND: Although self-harm and sleep problems are major public health
      problems in adolescence, detailed epidemiological assessment is essential to
      understand the nature of this relationship. AIMS: To conduct a detailed
      assessment of the relationship between sleep and self-harm in adolescence.
      METHOD: A large population-based study in Norway surveyed 10 220 adolescents aged
      16-19 years on mental health, including a comprehensive assessment of sleep and
      self-harm. RESULTS: Adolescents with sleep problems were significantly more
      likely to report self-harm than those without sleep problems. Insomnia, short
      sleep duration, long sleep onset latency, wake after sleep on set as well as
      large differences between weekdays versus weekends, yielded higher odds of self
      harm consistent with a dose-response relationship. Depressive symptoms accounted
      for some, but not all, of this association. CONCLUSIONS: The findings highlight a
      strong relationship between sleep problems and self-harm. Interventions to reduce
      adolescent self-harm ought to incorporate sleep problems as a treatment target.

PMID- 26206863
TI  - Loci with genome-wide associations with schizophrenia in the Han Chinese
      population.
AB  - BACKGROUND: A large schizophrenia genome-wide association study (GWAS) and a
      subsequent extensive replication study of individuals of European ancestry
      identified eight new loci with genome-wide significance and suggested that the
      MIR137-mediated pathway plays a role in the predisposition for schizophrenia.
      AIMS: To validate the above findings in a Han Chinese population. METHOD: We
      analysed the single nucleotide polymorphisms (SNPs) in the newly identified
      schizophrenia candidate loci and predicted MIR137 target genes based on our
      published Han Chinese populations (BIOX) GWAS data. We then analysed 18 SNPs from
      the candidate regions in an independent cohort that consisted of 3585 patients
      with schizophrenia and 5496 controls of Han Chinese ancestry. RESULTS: We
      replicated the associations of five markers (P<0.05), including three that were
      located in the predicted MIR137 target genes. Two loci (ITIH3/4: rs2239547, P =
      1.17 * 10(-10) and CALN1: rs2944829, P = 9.97 * 10(-9)) exhibited genome-wide
      significance in the Han Chinese population. CONCLUSIONS: The ITIH3/4 locus has
      been reported to be of genome-wide significance in the European population. The
      successful replication of this finding in a different ethnic group provides
      stronger evidence for the association between schizophrenia and ITIH3/4. We
      detected the first genome-wide significant association of schizophrenia with
      CALN1, which is a predicted target of MIR137, and thus provide new evidence for
      the associations between MIR137 targets and schizophrenia.

PMID- 26206861
TI  - Frontal slow-wave activity as a predictor of negative symptoms, cognition and
      functional capacity in schizophrenia.
AB  - BACKGROUND: Increased temporal and frontal slow-wave delta (1-4 Hz) and theta (4
      7 Hz) activities are the most consistent resting-state neural abnormalities
      reported in schizophrenia. The frontal lobe is associated with negative symptoms
      and cognitive abilities such as attention, with negative symptoms and impaired
      attention associated with poor functional capacity. AIMS: To establish whether
      frontal dysfunction, as indexed by slowing, would be associated with functional
      impairments. METHOD: Eyes-closed magnetoencephalography data were collected in 41
      participants with schizophrenia and 37 healthy controls, and frequency-domain
      source imaging localised delta and theta activity. RESULTS: Elevated delta and
      theta activity in right frontal and right temporoparietal regions was observed in
      the schizophrenia v. CONTROL GROUP: In schizophrenia, right-frontal delta
      activity was uniquely associated with negative but not positive symptoms. In the
      full sample, increased right-frontal delta activity predicted poorer attention
      and functional capacity. CONCLUSIONS: Our findings suggest that treatment
      associated decreases in slow-wave activity could be accompanied by improved
      functional outcome and thus better prognosis.

PMID- 26206864
TI  - Physical exercise for late-life major depression.
AB  - BACKGROUND: Interventions including physical exercise may help improve the
      outcomes of late-life major depression, but few studies are available. AIMS: To
      investigate whether augmenting sertraline therapy with physical exercise leads to
      better outcomes of late-life major depression. METHOD: Primary care patients (465
      years) with major depression were randomised to 24 weeks of higher-intensity,
      progressive aerobic exercise plus sertraline (S+PAE), lower-intensity, non
      progressive exercise plus sertraline (S+NPE) and sertraline alone. The primary
      outcome was remission (a score of <=10 on the Hamilton Rating Scale for
      Depression). RESULTS: A total of 121 patients were included. At study end, 45% of
      participants in the sertraline group, 73% of those in the S+NPE group and 81% of
      those in the S+PAE group achieved remission (P = 0.001). A shorter time to
      remission was observed in the S+PAE group than in the sertraline-only group.
      CONCLUSIONS: Physical exercise may be a safe and effective augmentation to
      antidepressant therapy in late-life major depression.

PMID- 26206865
TI  - Adolescent eating disorder behaviours and cognitions: gender-specific effects of
      child, maternal and family risk factors.
AB  - BACKGROUND: Eating disorder behaviours begin in adolescence. Few longitudinal
      studies have investigated childhood risk and protective FACTORS. AIMS: To
      investigate the prevalence of eating disorder behaviours and cognitions and
      associated childhood psychological, physical and parental risk factors among a
      cohort of 14-year-old children. METHOD: Data were collected from 6140 boys and
      girls aged 14 years. Gender-stratified models were used to estimate prospective
      associations between childhood body dissatisfaction, body mass index (BMI), self
      esteem, maternal eating disorder and family economic disadvantage on adolescent
      eating disorder behaviours and cognitions. RESULTS: Childhood body
      dissatisfaction strongly predicted eating disorder cognitions in girls, but only
      in interaction with BMI in boys. Higher self-esteem had a protective effect,
      particularly in boys. Maternal eating disorder predicted body dissatisfaction and
      weight/shape concern in adolescent girls and dieting in boys. CONCLUSIONS: Risk
      factors for eating disorder behaviours and cognitions vary according to gender.
      Prevention strategies should be gender-specific and target modifiable predictors
      in childhood and early adolescence.

PMID- 26206866
TI  - Ethnic inequalities in the use of secondary and tertiary mental health services
      among patients with obsessive-compulsive disorder.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) has similar prevalence rates
      across ethnic groups. However, ethnic minorities are underrepresented in clinical
      trials of OCD. It is unclear whether this is also the case in clinical services.
      AIMS: To explore whether ethnic minorities with OCD are underrepresented in
      secondary and tertiary mental health services in the South London and Maudsley
      (SLaM) NHS Foundation Trust. METHOD: The ethnic distribution of patients with OCD
      seen between 1999 and 2013 in SLaM (n = 1528) was compared with that of the
      general population in the catchment area using census data. A cohort of patients
      with depression (n = 22 716) was used for comparative purposes. RESULTS: Ethnic
      minorities with OCD were severely underrepresented across services (-57%, 95% CI 
      62% to -52%). The magnitude of the observed inequalities was significantly more
      pronounced than in depression (-29%, 95% CI -31% to -27%). CONCLUSIONS: There is
      a clear need to understand the reasons behind such ethnic inequalities and
      implement measures to reduce them.

PMID- 26206867
TI  - EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented
      Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation
      TKIs.
AB  - PURPOSE: Lung cancers harboring common EGFR mutations respond to EGFR tyrosine
      kinase inhibitors (TKI), whereas exon 20 insertions (Ins20) are resistant to
      them. However, little is known about mutations in exon 18. EXPERIMENTAL DESIGN:
      Mutational status of lung cancers between 2001 and 2015 was reviewed. Three
      representative mutations in exon 18, G719A, E709K, and exon 18 deletion (Del18:
      delE709_T710insD) were retrovirally introduced into Ba/F3 and NIH/3T3 cells. The
      90% inhibitory concentrations (IC90s) of first-generation (1G; gefitinib and
      erlotinib), second-generation (2G; afatinib, dacomitinib, and neratinib), and
      third-generation TKIs (3G; AZD9291 and CO1686) were determined. RESULTS: Among
      1,402 EGFR mutations, Del19, L858R, and Ins20 were detected in 40%, 47%, and 4%,
      respectively. Exon 18 mutations, including G719X, E709X, and Del18, were present
      in 3.2%. Transfected Ba/F3 cells grew in the absence of IL3, and NIH/3T3 cells
      formed foci with marked pile-up, indicating their oncogenic abilities. IC90s of
      1G and 3G TKIs in G719A, E709K, and Del18 were much higher than those in Del19
      (by >11-50-fold), whereas IC90s of afatinib were only 3- to 7-fold greater than
      those for Del19. Notably, cells transfected with G719A and E709K exhibited higher
      sensitivity to neratinib (by 5-25-fold) than those expressing Del19. Patients
      with lung cancers harboring G719X exhibited higher response rate to afatinib or
      neratinib (~ 80%) than to 1G TKIs (35%-56%) by compilation of data in the
      literature. CONCLUSIONS: Lung cancers harboring exon 18 mutations should not be
      overlooked in clinical practice. These cases can be best treated with afatinib or
      neratinib, although the currently available in vitro diagnostic kits cannot
      detect all exon 18 mutations.

PMID- 26206868
TI  - Nintedanib Is a Highly Effective Therapeutic for Neuroendocrine Carcinoma of the
      Pancreas (PNET) in the Rip1Tag2 Transgenic Mouse Model.
AB  - PURPOSE: Pancreatic neuroendocrine tumors (PNET) represent a rare but challenging
      heterogeneous group of cancers with an increasing incidence over the last number
      of decades. Herein, we report an in-depth evaluation of the new antiangiogenic
      small-molecule tyrosine kinase inhibitor (TKI) nintedanib in the preclinical
      Rip1Tag2 transgenic mouse model of neuroendocrine carcinoma of the pancreas
      (insulinoma). EXPERIMENTAL DESIGN: We have assessed the antiangiogenic and
      antitumor activity of nintedanib, in comparison with other antiangiogenic TKI, by
      treating Rip1Tag2 transgenic mice with different treatment schedules complemented
      with histopathologic, cell biologic, and biochemical analyses. RESULTS: Prolonged
      nintedanib treatment of Rip1Tag2 mice has led to a strong suppression of
      angiogenesis, accompanied by a reduced tumor burden, which translated into a
      significant prolongation of survival. Despite nintedanib's inhibitory action on
      perivascular cells, the blood vessels remaining after therapy displayed a
      considerably mature phenotype with tight perivascular cell coverage and preserved
      perfusion. Nintedanib treatment did not increase local tumor invasiveness or
      metastasis to the liver and pancreatic lymph nodes--a phenomenon that has been
      observed with antiangiogenic treatments of Rip1Tag2 transgenic mice in other
      laboratories. In contrast with the strong reduction in blood microvessel
      densities, nintedanib did not have any impact on tumor lymphangiogenesis.
      CONCLUSIONS: Based on our findings, we propose the clinical evaluation of the
      antiangiogenic drug nintedanib as a new treatment modality for PNET patients,
      notably in a direct comparison with already established therapeutic regimens,
      such as sunitinib.

PMID- 26206869
TI  - LOXL2 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor
      Colon Cancer Survival.
AB  - PURPOSE: Cancer-associated fibroblasts (CAF) are major mediators in tumor
      microenvironment. We investigated the changes in protein expression in colon
      cancer-associated fibroblasts compared with normal fibroblasts (NF) in the
      context of searching for prognostic biomarkers, particularly for stage II
      patients. EXPERIMENTAL DESIGN: CAFs and NFs isolated from colon cancer patients
      were used to identify differentially expressed proteins using quantitative
      proteomics. Stromal expression of deregulated proteins was analyzed by IHC.
      Prognostic impact was studied using external gene-expression datasets for
      training, then quantitative PCR and IHC for validation in different cohorts of
      patients. Combined datasets were used for prediction of risk assessment at stages
      II and III. RESULTS: A desmoplastic signature composed of 32 proteins, highly
      specific for stromal components in colon cancer, was identified. These proteins
      were enriched for extracellular matrix organization components, TGFbeta signaling
      pathway, fibrosis, and wound-healing proteins. The expression in CAFs of 11
      upregulated proteins and four downregulated proteins, selected for biomarker
      validation, was verified by orthogonal techniques. LOXL2 displayed a high
      prognostic impact by using external independent datasets and further validation
      in two different cohorts of patients. High expression of LOXL2 was associated
      with higher recurrence P = 0.001 HR, 5.38 [95% confidence interval (CI), 1.70
      17.01] and overall survival P = 0.001 HR, 8.52 (95% CI, 1.90-38.29). IHC analysis
      revealed a prognostic value for LOXL2 in stage II patients. CONCLUSIONS: We
      identified LOXL2 to be associated with the outcome of colon cancer patients.
      Furthermore, it can be used to stratify patients at stages II and III for further
      therapeutic decisions.

PMID- 26206870
TI  - High D-dimer levels after stopping anticoagulants in pulmonary embolism with
      sleep apnoea.
AB  - Obstructive sleep apnoea is a risk factor for pulmonary embolism. Elevated D
      dimer levels and other biomarkers are associated with recurrent pulmonary
      embolism. The objectives were to compare the frequency of elevated D-dimer levels
      (>500 ng.mL(-1)) and further coagulation biomarkers after oral anticoagulation
      withdrawal in pulmonary embolism patients, with and without obstructive sleep
      apnoea, including two control groups without pulmonary embolism.We performed home
      respiratory polygraphy. We also measured basic biochemical profile and haemogram,
      and coagulation biomarkers (D-dimer, prothrombin fragment 1+2, thrombin
      antithrombin complex, plasminogen activator inhibitor 1, and soluble P
      selectin).64 (74.4%) of the pulmonary embolism cases and 41 (46.11%) of the
      controls without pulmonary embolism had obstructive sleep apnoea. Plasmatic D
      dimer was higher in PE patients with OSA than in those without obstructive sleep
      apnoea. D-dimer levels were significantly correlated with apnoea-hypopnoea index,
      and nocturnal hypoxia. There were more patients with high D-dimer after stopping
      anticoagulants in those with pulmonary embolism and obstructive sleep apnoea
      compared with PE without obstructive sleep apnoea (35.4% versus 19.0%, p=0.003).
      Apnoea-hypopnoea index was independently associated with high D-dimer.Pulmonary
      embolism patients with obstructive sleep apnoea had higher rates of elevated D
      dimer levels after anticoagulation discontinuation for pulmonary embolism than in
      patients without obstructive sleep apnoea and, therefore, higher procoagulant
      state that might increase the risk of pulmonary embolism recurrence. 

PMID- 26206871
TI  - Allergen-induced airway responses.
AB  - Environmental allergens are an important cause of asthma and can contribute to
      loss of asthma control and exacerbations. Allergen inhalation challenge has been
      a useful clinical model to examine the mechanisms of allergen-induced airway
      responses and inflammation. Allergen bronchoconstrictor responses are the early
      response, which reaches a maximum within 30 min and resolves by 1-3 h, and late
      responses, when bronchoconstriction recurs after 3-4 h and reaches a maximum over
      6-12 h. Late responses are followed by an increase in airway hyperresponsiveness.
      These responses occur when IgE on mast cells is cross-linked by an allergen,
      causing degranulation and the release of histamine, neutral proteases and
      chemotactic factors, and the production of newly formed mediators, such as
      cysteinyl leukotrienes and prostaglandin D2. Allergen-induced airway inflammation
      consists of an increase in airway eosinophils, basophils and, less consistently,
      neutrophils. These responses are mediated by the trafficking and activation of
      myeloid dendritic cells into the airways, probably as a result of the release of
      epithelial cell-derived thymic stromal lymphopoietin, and the release of pro
      inflammatory cytokines from type 2 helper T-cells. Allergen inhalation challenge
      has also been a widely used model to study potential new therapies for asthma and
      has an excellent negative predictive value for this purpose. 

PMID- 26206874
TI  - Demand for exercise training in patients with pulmonary arterial hypertension in
      Scotland.

PMID- 26206873
TI  - Benefits of physical activity on COPD hospitalisation depend on intensity.
AB  - The present study aims to disentangle the independent effects of the quantity and
      the intensity of physical activity on the risk reduction of chronic obstructive
      pulmonary disease (COPD) hospitalisations.177 patients from the Phenotype
      Characterization and Course of COPD (PAC-COPD) cohort (mean+/-sd age 71+/-8
      years, forced expiratory volume in 1 s 52+/-16% predicted) wore the SenseWear Pro
      2 Armband accelerometer (BodyMedia, Pittsburgh, PA, USA) for eight consecutive
      days, providing data on quantity (steps per day, physically active days and daily
      active time) and intensity (average metabolic equivalent tasks) of physical
      activity. Information on COPD hospitalisations during follow-up (2.5+/-0.8 years)
      was obtained from validated centralised datasets. During follow-up 67 (38%)
      patients were hospitalised. There was an interaction between quantity and
      intensity of physical activity in their effects on COPD hospitalisation risk.
      After adjusting for potential confounders in the Cox regression model, the risk
      of COPD hospitalisation was reduced by 20% (hazard ratio (HR) 0.79, 95% CI 0.67
      0.93; p=0.005) for every additional 1000 daily steps at low average intensity. A
      greater quantity of daily steps at high average intensity did not influence the
      risk of COPD hospitalisations (HR 1.01, p=0.919). Similar results were found for
      the other measures of quantity of physical activity. Greater quantity of low
      intensity physical activity reduces the risk of COPD hospitalisation, but high
      intensity physical activity does not produce any risk reduction.

PMID- 26206872
TI  - A summary of the new GINA strategy: a roadmap to asthma control.
AB  - Over the past 20 years, the Global Initiative for Asthma (GINA) has regularly
      published and annually updated a global strategy for asthma management and
      prevention that has formed the basis for many national guidelines. However,
      uptake of existing guidelines is poor. A major revision of the GINA report was
      published in 2014, and updated in 2015, reflecting an evolving understanding of
      heterogeneous airways disease, a broader evidence base, increasing interest in
      targeted treatment, and evidence about effective implementation approaches.
      During development of the report, the clinical utility of recommendations and
      strategies for their practical implementation were considered in parallel with
      the scientific evidence.This article provides a summary of key changes in the
      GINA report, and their rationale. The changes include a revised asthma
      definition; tools for assessing symptom control and risk factors for adverse
      outcomes; expanded indications for inhaled corticosteroid therapy; a framework
      for targeted treatment based on phenotype, modifiable risk factors, patient
      preference, and practical issues; optimisation of medication effectiveness by
      addressing inhaler technique and adherence; revised recommendations about written
      asthma action plans; diagnosis and initial treatment of the asthma-chronic
      obstructive pulmonary disease overlap syndrome; diagnosis in wheezing pre-school
      children; and updated strategies for adaptation and implementation of GINA
      recommendations.

PMID- 26206875
TI  - Mefloquine as a potential drug against multidrug-resistant tuberculosis.

PMID- 26206876
TI  - Pulmonary tumour thrombotic microangiopathy: unclassifiable pulmonary
      hypertension?

PMID- 26206877
TI  - Gender differences in adult-onset asthma: results from the Swiss SAPALDIA cohort
      study.
AB  - A higher incidence of asthma is reported in women compared with men, but evidence
      in later adulthood is limited. We aimed to determine the 20-year cumulative
      incidence of adult asthma in Switzerland and its relation to sex, taking into
      account age and allergic sensitisation.We assessed incidence of self-report of
      doctor-diagnosed asthma between 1991/1992 and 2010/2011 in 5128 subjects without
      asthma, aged 18-60 years at baseline. The age-related probability of asthma onset
      was analysed by logistic regression adjusting for potential confounders and
      stratified by sex and allergic sensitisation at baseline.Over 20 years, 128
      (5.1%) men and 198 (7.5%) women newly reported doctor-diagnosed asthma. The
      adjusted odds ratio for female sex was 1.99 (95% CI 1.54-2.57) overall, 3.21 (95%
      CI 2.12-4.85) among nonsensitised subjects, and 1.43 (95% CI 1.02-2.02) in
      sensitised subjects. The probability of asthma onset decreased with increasing
      baseline age in women but not in men. The higher probability of new asthma in
      sensitised compared with nonsensitised men was unrelated to age, whereas in women
      it decreased with age.Asthma incidence was higher in women than in men but
      decreased with increasing age. The female predominance was considerably stronger
      in nonsensitised adults compared with those with allergic sensitisation.

PMID- 26206878
TI  - Incidence of rhinitis and asthma related to welding in Northern Europe.
AB  - Welding-related asthma is well recognised but less is known about rhinitis in
      relation to welding. The aim here, was to study associations between welding,
      rhinitis and asthma in a general population sample, and factors influencing
      selection into and out of a welding occupation.Adult-onset asthma and non
      infectious rhinitis were investigated in the international multicentre population
      based Respiratory Health in Northern Europe (RHINE) study, including 16,191
      responders aged 26-54 years. Ever welding (n=2181), welding >25% of working time
      (n=747), and welding in stainless steel >6 months (n=173) were assessed by
      questionnaire. Subjects with rhinitis or asthma onset when aged <18 years were
      excluded. Incidence rates for asthma and rhinitis were calculated from year of
      disease onset, and start and end of welding job. Cox's proportional hazard models
      adjusting for age, sex, parental education and study centre, and Kaplan-Meier
      curves were used.Rhinitis incidence was higher among welders (hazard ratio (HR)
      1.4, 95% CI 1.3-1.6), consistent in men and women, and across centres
      (pheterogeneity=0.4). In men, asthma incidence was higher among welders (HR 1.4,
      95% CI 1.04-1.97). Quitting welding was indicated higher after adult-onset
      rhinitis (HR 1.1, 95% CI 1.0-1.3). Adult-onset rhinitis and asthma was higher
      among welders, consistent across population samples from Northern Europe. No pre
      employment selection was found, whereas selection out of welding jobs was
      suggested.

PMID- 26206879
TI  - Discordance between the QuantiFERON-TB Gold In-Tube and Tuberculin Skin Test:
      need for a further step?

PMID- 26206881
TI  - Defining the urban area for cross national comparison of health indicators: the
      EURO-URHIS 2 boundary study.
AB  - Introduction: Despite much research focusing on the impact of the city condition
      upon health, there still remains a lack of consensus over what constitutes an
      urban area (UA). This study was conducted to establish comparable boundaries for
      the UAs participating in EURO-URHIS 2, and to test whether the sample reflected
      the heterogeneity of urban living. Key UA contacts ( n = 28) completed a cross
      sectional questionnaire, which included where available comparison between Urban
      Audit city and larger urban zone (LUZ) boundaries and public health
      administration areas (PHAAs). Additionally, broad health and demographic
      indicators were sought to test for heterogeneity of the EURO-URHIS 2 sample.
      Urban Audit city boundaries were found to be suitable for data collection in 100%
      ( n = 21) of UAs where Urban Audit data were available. The remainder ( n = 7)
      identified PHAA boundaries akin to the 'city' level. Heterogeneity was observed
      in the sample for population size and infant mortality rate. Heterogeneity could
      not be established for male and female life expectancy. This study was able to
      establish comparable boundaries for EURO-URHIS 2 data collection, with the 'city'
      area being selected for data collection. The homogeneity of life expectancy
      indicators was reflective of sub-regional similarities in life expectancy, whilst
      population estimates and rates of infant mortality indicated the presence of
      heterogeneity within the sample. Future work would trial these methods with a
      larger number of indicators and for a larger number of UAs.

PMID- 26206880
TI  - Nasal decongestant exposure in patients with pulmonary arterial hypertension: a
      pilot study.

PMID- 26206882
TI  - Diagnostic Accuracy of Noninvasive Genotyping of EGFR in Lung Cancer Patients by
      Deep Sequencing of Plasma Cell-Free DNA.
AB  - BACKGROUND: Genotyping of EGFR (epidermal growth factor receptor) mutations is
      indispensable for making therapeutic decisions regarding whether to use EGFR
      tyrosine kinase inhibitors (TKIs) for lung cancer. Because some cases might pose
      challenges for biopsy, noninvasive genotyping of EGFR in circulating tumor DNA
      (ctDNA) would be beneficial for lung cancer treatment. METHODS: We developed a
      detection system for EGFR mutations in ctDNA by use of deep sequencing of plasma
      DNA. Mutations were searched in >100 000 reads obtained from each exon region.
      Parameters corresponding to the limit of detection and limit of quantification
      were used as the thresholds for mutation detection. We conducted a multi
      institute prospective study to evaluate the detection system, enrolling 288 non
      small cell lung cancer (NSCLC) patients. RESULTS: In evaluating the performance
      of the detection system, we used the genotyping results from biopsy samples as a
      comparator: diagnostic sensitivity for exon 19 deletions, 50.9% (95% CI 37.9%
      63.9%); diagnostic specificity for exon 19 deletions, 98.0% (88.5%-100%);
      sensitivity for the L858R mutation, 51.9% (38.7%-64.9%); and specificity for
      L858R, 94.1% (83.5%-98.6%). The overall sensitivities were as follows: all cases,
      54.4% (44.8%-63.7%); stages IA-IIIA, 22.2% (11.5%-38.3%); and stages IIIB-IV,
      72.7% (60.9%-82.1%). CONCLUSIONS: Deep sequencing of plasma DNA can be used for
      genotyping of EGFR in lung cancer patients. In particular, the high specificity
      of the system may enable a direct recommendation for EGFR-TKI on the basis of
      positive results with plasma DNA. Because sensitivity was low in early-stage
      NSCLC, the detection system is preferred for stage IIIB-IV NSCLC.

PMID- 26206883
TI  - Nonfasting Lipid Profiles: The Way of the Future.

PMID- 26206885
TI  - Rescue of the abnormal skeletal phenotype in Ts65Dn Down syndrome mice using
      genetic and therapeutic modulation of trisomic Dyrk1a.
AB  - Trisomy 21 causes skeletal alterations in individuals with Down syndrome (DS),
      but the causative trisomic gene and a therapeutic approach to rescue these
      abnormalities are unknown. Individuals with DS display skeletal alterations
      including reduced bone mineral density, modified bone structure and distinctive
      facial features. Due to peripheral skeletal anomalies and extended longevity,
      individuals with DS are increasingly more susceptible to bone fractures.
      Understanding the genetic and developmental origin of DS skeletal abnormalities
      would facilitate the development of therapies to rescue these and other
      deficiencies associated with DS. DYRK1A is found in three copies in individuals
      with DS and Ts65Dn DS mice and has been hypothesized to be involved in many
      Trisomy 21 phenotypes including skeletal abnormalities. Return of Dyrk1a copy
      number to normal levels in Ts65Dn mice rescued the appendicular bone
      abnormalities, suggesting that appropriate levels of DYRK1A expression are
      critical for the development and maintenance of the DS appendicular skeleton.
      Therapy using the DYRK1A inhibitor epigallocatechin-3-gallate improved Ts65Dn
      skeletal phenotypes. These outcomes suggest that the osteopenic phenotype
      associated with DS may be rescued postnatally by targeting trisomic Dyrk1a. 

PMID- 26206884
TI  - Genomic analysis reveals distinct mechanisms and functional classes of SOX10
      regulated genes in melanocytes.
AB  - SOX10 is required for melanocyte development and maintenance, and has been linked
      to melanoma initiation and progression. However, the molecular mechanisms by
      which SOX10 guides the appropriate gene expression programs necessary to promote
      the melanocyte lineage are not fully understood. Here we employ genetic and
      epigenomic analysis approaches to uncover novel genomic targets and previously
      unappreciated molecular roles of SOX10 in melanocytes. Through global analysis of
      SOX10-binding sites and epigenetic characteristics of chromatin states, we
      uncover an extensive catalog of SOX10 targets genome-wide. Our findings reveal
      that SOX10 predominantly engages 'open' chromatin regions and binds to distal
      regulatory elements, including novel and previously known melanocyte enhancers.
      Integrated chromatin occupancy and transcriptome analysis suggest a role for
      SOX10 in both transcriptional activation and repression to regulate functionally
      distinct classes of genes. We demonstrate that distinct epigenetic signatures and
      cis-regulatory sequence motifs predicted to bind putative co-regulatory
      transcription factors define SOX10-activated and SOX10-repressed target genes.
      Collectively, these findings uncover a central role of SOX10 as a global
      regulator of gene expression in the melanocyte lineage by targeting diverse
      regulatory pathways. 

PMID- 26206886
TI  - Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in
      dysferlinopathy.
AB  - Myostatin is a secreted signaling molecule that normally acts to limit muscle
      growth. As a result, there is extensive effort directed at developing drugs
      capable of targeting myostatin to treat patients with muscle loss. One potential
      concern with this therapeutic approach in patients with muscle degenerative
      diseases like muscular dystrophy is that inducing hypertrophy may increase stress
      on dystrophic fibers, thereby accelerating disease progression. To investigate
      this possibility, we examined the effect of blocking the myostatin pathway in
      dysferlin-deficient (Dysf(-/-)) mice, in which membrane repair is compromised,
      either by transgenic expression of follistatin in skeletal muscle or by systemic
      administration of the soluble form of the activin type IIB receptor (ACVR2B/Fc).
      Here, we show that myostatin inhibition by follistatin transgene expression in
      Dysf(-/-) mice results in early improvement in histopathology but ultimately
      exacerbates muscle degeneration; this effect was not observed in dystrophin
      deficient (mdx) mice, suggesting that accelerated degeneration induced by
      follistatin transgene expression is specific to mice lacking dysferlin. Dysf(-/-)
      mice injected with ACVR2B/Fc showed significant increases in muscle mass and
      amelioration of fibrotic changes normally seen in 8-month-old Dysf(-/-) mice.
      Despite these potentially beneficial effects, ACVR2B/Fc treatment caused
      increases in serum CK levels in some Dysf(-/-) mice, indicating possible muscle
      damage induced by hypertrophy. These findings suggest that depending on the
      disease context, inducing muscle hypertrophy by myostatin blockade may have
      detrimental effects, which need to be weighed against the potential gains in
      muscle growth and decreased fibrosis. 

PMID- 26206887
TI  - Lyso-Gb3 activates Notch1 in human podocytes.
AB  - Podocyte injury is an early feature of Fabry nephropathy, but the molecular
      mechanisms of podocyte injury are poorly understood. Lyso-Gb3 accumulates in
      serum in Fabry disease and increases extracellular matrix synthesis in podocytes.
      We explored the contribution of Notch1 signaling, a mediator of podocyte injury,
      to lyso-Gb3-elicited responses in cultured human podocytes. At clinically
      relevant concentrations, lyso-Gb3 activates podocyte Notch1 signaling, resulting
      in increased active Notch1 and HES1, a canonical Notch transcriptional target. A
      gamma-secretase inhibitor or specific Notch1 small interfering RNA (siRNA)
      inhibited HES1 upregulation in response to lyso-Gb3. Notch1 siRNA or gamma
      secretase inhibition also prevented the lyso-Gb3-induced upregulation of Notch1,
      Notch ligand Jagged1 and chemokine (MCP1, RANTES) expression. Notch siRNA
      prevented the activation of nuclear factor kappa B (NFkappaB), and NFkappaB
      activation contributed to Notch1-mediated inflammatory responses as the NFkappaB
      inhibitor, parthenolide, prevented lyso-Gb3-induced chemokine upregulation.
      Notch1 also mediates fibrogenic responses in podocytes as Notch siRNA prevented
      lyso-Gb3 upregulation of fibronectin mRNA. Supporting the clinical relevance of
      cell culture findings, active Notch1, Jagged1 and HES1 were observed in Fabry
      kidney biopsies. Lyso-Gb3 elicited similar responses in mouse kidney. In
      conclusion, lyso-Gb3 promotes Notch1-mediated inflammatory and fibrogenic
      responses in podocytes that may contribute to Fabry nephropathy. 

PMID- 26206888
TI  - N-acetylcysteine treatment ameliorates the skeletal phenotype of a mouse model of
      diastrophic dysplasia.
AB  - Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by mutations
      in SLC26A2, a cell membrane sulfate-chloride antiporter. Sulfate uptake
      impairment results in low cytosolic sulfate, leading to cartilage proteoglycan
      (PG) undersulfation. In this work, we used the dtd mouse model to study the role
      of N-acetyl-l-cysteine (NAC), a well-known drug with antioxidant properties, as
      an intracellular sulfate source for macromolecular sulfation. Because of the
      important pre-natal phase of skeletal development and growth, we administered 30
      g/l NAC in the drinking water to pregnant mice to explore a possible
      transplacental effect on the fetuses. When cartilage PG sulfation was evaluated
      by high-performance liquid chromatography disaccharide analysis in dtd newborn
      mice, a marked increase in PG sulfation was observed in newborns from NAC-treated
      pregnancies when compared with the placebo group. Morphometric studies of the
      femur, tibia and ilium after skeletal staining with alcian blue and alizarin red
      indicated a partial rescue of abnormal bone morphology in dtd newborns from
      treated females, compared with pups from untreated females. The beneficial effect
      of increased macromolecular sulfation was confirmed by chondrocyte proliferation
      studies in cryosections of the tibial epiphysis by proliferating cell nuclear
      antigen immunohistochemistry: the percentage of proliferating cells,
      significantly reduced in the placebo group, reached normal values in dtd newborns
      from NAC-treated females. In conclusion, NAC is a useful source of sulfate for
      macromolecular sulfation in vivo when extracellular sulfate supply is reduced,
      confirming the potential of therapeutic approaches with thiol compounds to
      improve skeletal deformity and short stature in human DTD and related disorders. 

PMID- 26206889
TI  - SMN expression is required in motor neurons to rescue electrophysiological
      deficits in the SMNDelta7 mouse model of SMA.
AB  - Proximal spinal muscular atrophy (SMA) is the most frequent cause of hereditary
      infant mortality. SMA is an autosomal recessive neuromuscular disorder that
      results from the loss of the Survival Motor Neuron 1 (SMN1) gene and retention of
      the SMN2 gene. The SMN2 gene produces an insufficient amount of full-length SMN
      protein that results in loss of motor neurons in the spinal cord and subsequent
      muscle paralysis. Previously we have shown that overexpression of human SMN in
      neurons in the SMA mouse ameliorates the SMA phenotype while overexpression of
      human SMN in skeletal muscle had no effect. Using Cre recombinase, here we show
      that either deletion or replacement of Smn in motor neurons (ChAT-Cre)
      significantly alters the functional output of the motor unit as measured with
      compound muscle action potential and motor unit number estimation. However ChAT
      Cre alone did not alter the survival of SMA mice by replacement and did not
      appreciably affect survival when used to deplete SMN. However replacement of Smn
      in both neurons and glia in addition to the motor neuron (Nestin-Cre and ChAT
      Cre) resulted in the greatest improvement in survival of the mouse and in some
      instances complete rescue was achieved. These findings demonstrate that high
      expression of SMN in the motor neuron is both necessary and sufficient for proper
      function of the motor unit. Furthermore, in the mouse high expression of SMN in
      neurons and glia, in addition to motor neurons, has a major impact on survival. 

PMID- 26206890
TI  - Mutations in the histamine N-methyltransferase gene, HNMT, are associated with
      nonsyndromic autosomal recessive intellectual disability.
AB  - Histamine (HA) acts as a neurotransmitter in the brain, which participates in the
      regulation of many biological processes including inflammation, gastric acid
      secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT)
      inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA,
      and is the only well-known pathway for termination of neurotransmission actions
      of HA in mammalian central nervous system. We performed autozygosity mapping
      followed by targeted exome sequencing and identified two homozygous HNMT
      alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic
      autosomal recessive intellectual disability from two unrelated consanguineous
      families of Turkish and Kurdish ancestry, respectively. We verified the complete
      absence of a functional HNMT in patients using in vitro toxicology assay. Using
      mutant and wild-type DNA constructs as well as in silico protein modeling, we
      confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and
      that p.Leu208Pro results in reduced protein stability, resulting in decreased HA
      inactivation. Our results highlight the importance of inclusion of HNMT for
      genetic testing of individuals presenting with intellectual disability. 

PMID- 26206892
TI  - Timing of Dialysis Initiation-Do Health Care Setting or Provider Incentives
      Matter?

PMID- 26206891
TI  - Trends in Timing of Dialysis Initiation within Versus Outside the Department of
      Veterans Affairs.
AB  - BACKGROUND AND OBJECTIVES: The secular trend toward dialysis initiation at
      progressively higher levels of eGFR is not well understood. This study compared
      temporal trends in eGFR at dialysis initiation within versus outside the
      Department of Veterans Affairs (VA)-the largest non-fee-for-service health system
      in the United States. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study
      used linked data from the US Renal Data System, VA, and Medicare to compare
      temporal trends in eGFR at dialysis initiation between 2000 and 2009 (n=971,543).
      Veterans who initiated dialysis within the VA were compared with three groups who
      initiated dialysis outside the VA: (1) veterans whose dialysis was paid for by
      the VA, (2) veterans whose dialysis was not paid for by the VA, and (3)
      nonveterans. Logistic regression was used to estimate average predicted
      probabilities of dialysis initiation at an eGFR>=10 ml/min per 1.73 m(2).
      RESULTS: The adjusted probability of starting dialysis at an eGFR>=10 ml/min per
      1.73 m(2) increased over time for all groups but was lower for veterans who
      started dialysis within the VA (0.31; 95% confidence interval [95% CI], 0.30 to
      0.32) than for those starting outside the VA, including veterans whose dialysis
      was (0.36; 95% CI, 0.35 to 0.38) and was not (0.40; 95% CI, 0.40 to 0.40) paid
      for by the VA and nonveterans (0.39; 95% CI, 0.39 to 0.39). Differences in eGFR
      at initiation within versus outside the VA were most pronounced among older
      patients (P for interaction <0.001) and those with a higher risk of 1-year
      mortality (P for interaction <0.001). CONCLUSIONS: Temporal trends in eGFR at
      dialysis initiation within the VA mirrored those in the wider United States
      dialysis population, but eGFR at initiation was consistently lowest among those
      who initiated within the VA. Differences in eGFR at initiation within versus
      outside the VA were especially pronounced in older patients and those with higher
      1-year mortality risk.

PMID- 26206893
TI  - Follow-up calls to next of kin relating to coronial autopsies.
AB  - It might be expected that follow-up telephone communication with next of kin
      relating to coronial autopsies would be distressing, particularly when made
      months or even years after the death. However, our experience has indicated that
      this is not the case in the majority of calls. 

PMID- 26206894
TI  - Prevalence of Endosymbionts in Polish Populations of Leptinotarsa decemlineata
      (Coleoptera: Chrysomelidae).
AB  - Colorado potato beetle (CPB, Leptinotarsa decemlineata Say) (Coleoptera:
      Chrysomelidae) is one of the most serious insect pest feeding on wild and
      cultivated Solanaceae plants. This pest poses a significant threat to potato
      crops. CPB originated from North America but has become widespread and has
      adapted in new localizations. Currently, it is reported in many countries
      worldwide. Endosymbiotic bacteria might have an influence on insect adaptation to
      new conditions. They are known to play a role in invasiveness of insect hosts and
      to facilitate colonization of new niches; however, information on endosymbionts
      of the CPB is very limited. In this study, we screened CPB populations collected
      from 20 evenly distributed locations in Poland for the presence of Arsenophonus,
      Cardinium, Wolbachia, and Flavobacterium. We found the presence of Flavobacterium
      in the studied insects. Little is known about CPB-endosymbionts interactions,
      thus this study may provide a reference for future studies in this subject. 

PMID- 26206895
TI  - Sexual Dimorphism and Allometric Effects Associated With the Wing Shape of Seven
      Moth Species of Sphingidae (Lepidoptera: Bombycoidea).
AB  - Sexual dimorphism is a pronounced pattern of intraspecific variation in
      Lepidoptera. However, moths of the family Sphingidae (Lepidoptera: Bombycoidea)
      are considered exceptions to this rule. We used geometric morphometric techniques
      to detect shape and size sexual dimorphism in the fore and hindwings of seven
      hawkmoth species. The shape variables produced were then subjected to a
      discriminant analysis. The allometric effects were measured with a simple
      regression between the canonical variables and the centroid size. We also used
      the normalized residuals to assess the nonallometric component of shape variation
      with a t-test. The deformations in wing shape between sexes per species were
      assessed with a regression between the nonreduced shape variables and the
      residuals. We found sexual dimorphism in both wings in all analyzed species, and
      that the allometric effects were responsible for much of the wing shape variation
      between the sexes. However, when we removed the size effects, we observed shape
      sexual dimorphism. It is very common for females to be larger than males in
      Lepidoptera, so it is expected that the shape of structures such as wings suffers
      deformations in order to preserve their function. However, sources of variation
      other than allometry could be a reflection of different reproductive flight
      behavior (long flights in search for sexual mates in males, and flight in search
      for host plants in females). 

PMID- 26206896
TI  - Population Dynamics of Aphthona whitfieldi (Coleoptera: Chrysomelidae), Pest of
      Jatropha curcas, and Environmental Factors Favoring Its Abundance in Burkina
      Faso.
AB  - The flea beetle Aphthona whitfieldi Bryant (Coleoptera: Chrysomelidae) is the
      main pest of the bioenergy crop Jatropha curcas L. (Euphorbiaceae) in Burkina
      Faso and several other West African countries. Adults severely defoliate plants,
      resulting in seedling mortality, poor growth, and low yields. To study the
      population dynamics of the pest in the Sissili Province of Burkina Faso, 12 sites
      were monitored weekly during a year and 31 sites were inspected for damage at the
      peak period of insect abundance. The effect of cropping systems (hedge,
      intercropping, and monoculture) and surrounding vegetation on population
      densities of A. whitfieldi was assessed. Beetles were rarely found in the dry
      season and peaked in the second half of the rainy season. The cropping system did
      not significantly influence the abundance and attack level. In contrast, the
      close vicinity of fallow lands seems to increase damage levels. Many aspects of
      the biology and ecology of A. whitfieldi remain to be investigated before
      sustainable control methods can be developed. However, this study already allows
      us to propose recommendations for further research on management. 

PMID- 26206897
TI  - A large-scale prospective registration study of the safety and efficacy of
      sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan:
      results of over 3200 consecutive cases in post-marketing all-patient
      surveillance.
AB  - OBJECTIVE: Real-life safety and efficacy of sorafenib in advanced renal cell
      carcinoma in a nationwide patient population were evaluated by post-marketing all
      patient surveillance. METHODS: All patients with unresectable or metastatic renal
      cell carcinoma in Japan who started sorafenib therapy from February 2008 to
      September 2009 were registered and followed for up to 12 months. Baseline
      characteristics, treatment status, tumor response, survival and safety data were
      recorded by the prescribing physicians. RESULTS: Safety and efficacy were
      evaluated in 3255 and 3171 patients, respectively. The initial daily dose was 800
      mg in 78.2% of patients. Median duration of treatment was 6.7 months and the mean
      relative dose intensity was 68.4%. Overall, 2227 patients (68.4%) discontinued
      the treatment by 12 months, half of which (52.0% of discontinued patients) were
      due to adverse events. The most common adverse drug reactions were hand-foot skin
      reaction (59%), hypertension (36%), rash (25%) and increase in lipase/amylase
      (23%). The median progression-free survival was 7.3 months (95% confidence
      intervals: 6.7-8.1), and the overall survival rate at 1 year was 75.4% (73.5
      77.1). Prognostic factors for overall survival were mostly consistent with those
      in previous clinical trials in the univariate analysis and largely similar to
      those for progression-free survival and duration of treatment in the multivariate
      analysis. CONCLUSIONS: Sorafenib for the treatment of advanced renal cell
      carcinoma under the labeled dose was feasible in daily medical practice, for its
      acceptable toxicity profile and favorable clinical benefit that were consistent
      with those in clinical trials.

PMID- 26206898
TI  - Clinicopathological features of classical Hodgkin lymphoma in patients >= 40
      years old, with special reference to composite cases.
AB  - OBJECTIVE: Classical Hodgkin lymphoma shows a peak incidence at 15-35 years, and
      a second peak in elderly patients; however, pathological characteristics of
      elderly patients with classical Hodgkin lymphoma have not been analyzed enough.
      METHODS: In a total of 154 patients with classical Hodgkin lymphoma, we analyzed
      the clinicopathological characteristics of classical Hodgkin lymphoma patients
      aged >= 40 years old, with special reference to the incidence, histopathology and
      outcome of patients with composite classical Hodgkin lymphoma. RESULTS: Of 154
      patients with classical Hodgkin lymphoma, 50 (32%) were >= 40 years old. The 5
      year progression-free and overall survival rates were 59 and 86%, respectively.
      Thirty-eight patients (76%) had non-composite classical Hodgkin lymphoma, 10
      patients (20%) had composite (6 simultaneous and 4 consecutive) classical Hodgkin
      lymphoma and B-cell non-Hodgkin lymphoma and 2 patients (4%) had methotrexate
      associated classical Hodgkin lymphoma. Of 10 patients with composite classical
      Hodgkin lymphoma, composite lymphomas were detected throughout the staging
      procedure of the upper gastrointestinal tract or bone marrow in 4 patients.
      Fluorescence in situ hybridization revealed that the composite lymphomas of 4, 1
      and 5 patients were related, unrelated and of unknown correlation status,
      respectively. The treatments after the diagnosis of a classical Hodgkin lymphoma
      component varied, and three patients died of lymphoma. CONCLUSIONS: We found that
      the incidence of composite classical Hodgkin lymphoma in patients >= 40 years old
      was 20%. Correct diagnosis and optimal treatment for patients with composite
      classical Hodgkin lymphoma and B-cell non-Hodgkin lymphoma is highly important in
      this patient population.

PMID- 26206899
TI  - Comparison of diagnostic accuracy between endometrial curettage and pipelle
      aspiration biopsy in patients treated with progestin for endometrial hyperplasia:
      a Korean Gynecologic Oncology Group Study (KGOG 2019).
AB  - A prospective multicenter trial has been started in Korea to evaluate the
      diagnostic accuracy of endometrial aspiration biopsy compared with dilatation and
      curettage in patients treated with progestin for endometrial hyperplasia. For
      conservative treatment of endometrial hyperplasia, orally administered progestins
      are most commonly used method with various treatment regimens and more recently,
      the levonorgestrel-releasing intrauterine system also has been used successfully
      to treat endometrial hyperplasia. However, there is no report about the accuracy
      of endometrial sampling during hormonal treatment for follow-up evaluation of
      endometrial hyperplasia. Patients with histologically confirmed endometrial
      hyperplasia are offered hormonal treatment with any one of the following three
      options: oral medroxyprogesterone acetate 10 mg/day for 14 days per cycle,
      continuous oral medroxyprogesterone acetate 10 mg/day or insertion of
      levonorgestrel-releasing intrauterine system. Histological surveillance is
      performed at 3 months or 6 months following initial treatment. Endometrial
      tissues are obtained via endometrial aspiration biopsy using a pipelle and
      dilatation and curettage. In the case of levonorgestrel-releasing intrauterine
      system, endometrial aspiration biopsy will be done with levonorgestrel-releasing
      intrauterine system in uterus and then, after the removal of levonorgestrel
      releasing intrauterine system, dilatation and curettage will be done. The biopsy
      findings will be compared. The primary endpoint is to compare the pathological
      outcome of endometrial aspiration with dilatation and curettage. The secondary
      endpoint is the response rate with three types of progestin treatment at 6
      months. 

PMID- 26206902
TI  - Rethinking graduate education.

PMID- 26206904
TI  - PLANETARY SCIENCE. Scientists ponder an improbably active Pluto.

PMID- 26206900
TI  - Endotoxin tolerance in monocytes can be mitigated by alpha2-interferon.
AB  - Endotoxin tolerance is characterized by diminished expression of inflammatory
      cytokines after sequential exposure to Toll-like receptor stimuli. Many
      mechanisms contribute to tolerance; however, chromatin remodeling appears to be
      the most significant regulator. The type II interferon, IFN-gamma, has been
      recognized as being able to reverse or abrogate the establishment of tolerance.
      Type I interferons have not been investigated previously, and they bind a
      distinct receptor. We found that alpha2-interferon was able to abrogate or
      diminish tolerance by endotoxin, as defined by measuring mRNA levels at
      recognized tolerance targets. We also found that alpha2-interferon treatment
      during tolerization was associated with increased H3K4me3 and H3K4me2 levels at
      promoters of tolerance targets in THP1 cells. These marks were normalized after
      exposure of the cells to alpha2-interferon. Interferon regulatory factor 1 is a
      transcription factor activated and induced by types I and II interferons. We
      found recruitment of this transcription factor paralleled tolerance and
      inhibition of tolerance at target genes. Therefore, there are at least 2 distinct
      pathways by which endotoxin tolerance may be mitigated. A type I interferon, in
      spite of binding to a different receptor, was just as able to inhibit tolerance
      as the type II interferon and also appeared to act by modifying chromatin at
      tolerance target genes. 

PMID- 26206905
TI  - HUMAN GENETICS. New mystery for Native American origins.

PMID- 26206901
TI  - Low-density lipoprotein receptor-related protein 1 mediates alpha1-antitrypsin
      internalization in CD4+ T lymphocytes.
AB  - In alpha1-antitrypsin-deficient HIV patients, an accelerated decline of CD4(+) T
      cell numbers is observed, suggesting that alpha1-antitrypsin is a potential
      endogenous HIV inhibitor. In infected T lymphocytes, alpha1-antitrypsin potently
      blocks NF-kappaB activation and HIV-1 replication by directly interacting with
      IkappaBalpha in the cytosol, thereby altering its ubiquitination pattern.
      However, the mechanism of alpha1-antitrypsin entry into the cytosol, where
      IkappaBalpha locates, remains unclear. In the present study, we investigated the
      mechanism of alpha1-antitrypsin internalization in CD4(+) T cells. Thus, primary
      CD4(+) T cells were infected with HIV-1 and then incubated with alpha1
      antitrypsin to detect its internalization. We found that CD4(+) T cells
      internalized alpha1-antitrypsin through a clathrin-dependent endocytosis process.
      Next, intracellular alpha1-antitrypsin exerted the inhibitory effect on NF-kappaB
      activation and HIV-1 replication. On primary CD4(+) T cells, alpha1-antitrypsin
      interacted with low-density lipoprotein receptor-related protein 1 to initiate
      the internalization. Inside CD4(+) T lymphocytes, alpha1-antitrypsin was
      transported from the endosome to the lysosome and then released into the cytosol,
      where it is possible for alpha1-antitrypsin to directly interact with
      IkappaBalpha. These results together suggest that alpha1-antitrypsin
      internalization is a clathrin-dependent and low-density lipoprotein receptor
      related protein 1-mediated endocytosis process. Internalized alpha1-antitrypsin
      is transported through the endosome-lysosome-cytosol routine to interact with
      cytosolic IkappaBalpha and block NF-kappaB activation and HIV-1 replication. 

PMID- 26206907
TI  - NUCLEAR DIPLOMACY. Iran nuclear deal holds 'goodies' for scientists.

PMID- 26206908
TI  - ASTRONOMY. Web billionaire bankrolls search for alien signals.

PMID- 26206906
TI  - HIV/AIDS. Child fights HIV to a draw.

PMID- 26206909
TI  - New life for old bones.

PMID- 26206910
TI  - Revolution in human evolution.

PMID- 26206911
TI  - Lost worlds found.

PMID- 26206912
TI  - Prospecting for genetic gold.

PMID- 26206913
TI  - Breaking a tropical taboo.

PMID- 26206914
TI  - Protein power.

PMID- 26206915
TI  - PALEONTOLOGY. Four legs too many?

PMID- 26206916
TI  - MICROBIAL ECOLOGY. Making methane down deep.

PMID- 26206917
TI  - IMMUNOLOGY. Moving CTLA-4 from the trash to recycling.

PMID- 26206918
TI  - CHEMISTRY. Catalysts by Platonic design.

PMID- 26206919
TI  - GENE REGULATION. Breakers and blockers-miRNAs at work.

PMID- 26206920
TI  - STRETCHABLE ELECTRONICS. Stretch, wrap, and relax to smartness.

PMID- 26206921
TI  - SCIENCE AND GOVERNMENT. Yellow lights for emerging technologies.

PMID- 26206922
TI  - PUBLIC HEALTH. Toward an HIV vaccine: A scientific journey.

PMID- 26206923
TI  - Precision medicine: Look to the mice.

PMID- 26206924
TI  - Sexism discussion misses the point.

PMID- 26206925
TI  - Chimpanzees deserve their freedom.

PMID- 26206926
TI  - WOMEN IN SCIENCE. Comment on "Expectations of brilliance underlie gender
      distributions across academic disciplines".
AB  - Leslie et al. (Reports, 16 January 2015, p. 262) concluded that "expectations of
      brilliance" explained the gender makeup of academic disciplines. We reestimated
      their models after adding measures of disaggregated Graduate Record Examination
      scores by field. Our results indicated that female representation among Ph.D.
      recipients is associated with the field's mathematical content and that faculty
      beliefs about innate ability were irrelevant. 

PMID- 26206927
TI  - WOMEN IN SCIENCE. Response to Comment on "Expectations of brilliance underlie
      gender distributions across academic disciplines".
AB  - Ginther and Kahn claim that academics' beliefs about the importance of brilliance
      do not predict gender gaps in Ph.D. attainment beyond mathematics and verbal test
      scores. However, Ginther and Kahn's analyses are problematic, exhibiting more
      than 100 times the recommended collinearity thresholds. Multiple analyses that
      avoid this problem suggest that academics' beliefs are in fact uniquely
      predictive of gender gaps across academia. 

PMID- 26206928
TI  - APPLIED ORIGAMI. Origami of thick panels.
AB  - Origami patterns, including the rigid origami patterns in which flat inflexible
      sheets are joined by creases, are primarily created for zero-thickness sheets. In
      order to apply them to fold structures such as roofs, solar panels, and space
      mirrors, for which thickness cannot be disregarded, various methods have been
      suggested. However, they generally involve adding materials to or offsetting
      panels away from the idealized sheet without altering the kinematic model used to
      simulate folding. We develop a comprehensive kinematic synthesis for rigid
      origami of thick panels that differs from the existing kinematic model but is
      capable of reproducing motions identical to that of zero-thickness origami. The
      approach, proven to be effective for typical origami, can be readily applied to
      fold real engineering structures. 

PMID- 26206930
TI  - QUANTUM INFORMATION. Coherent coupling of a single spin to microwave cavity
      photons.
AB  - Electron spins and photons are complementary quantum-mechanical objects that can
      be used to carry, manipulate, and transform quantum information. To combine these
      resources, it is desirable to achieve the coherent coupling of a single spin to
      photons stored in a superconducting resonator. Using a circuit design based on a
      nanoscale spin valve, we coherently hybridize the individual spin and charge
      states of a double quantum dot while preserving spin coherence. This scheme
      allows us to achieve spin-photon coupling up to the megahertz range at the single
      spin level. The cooperativity is found to reach 2.3, and the spin coherence time
      is about 60 nanoseconds. We thereby demonstrate a mesoscopic device suitable for
      nondestructive spin readout and distant spin coupling. 

PMID- 26206929
TI  - STRETCHY ELECTRONICS. Hierarchically buckled sheath-core fibers for superelastic
      electronics, sensors, and muscles.
AB  - Superelastic conducting fibers with improved properties and functionalities are
      needed for diverse applications. Here we report the fabrication of highly
      stretchable (up to 1320%) sheath-core conducting fibers created by wrapping
      carbon nanotube sheets oriented in the fiber direction on stretched rubber fiber
      cores. The resulting structure exhibited distinct short- and long-period sheath
      buckling that occurred reversibly out of phase in the axial and belt directions,
      enabling a resistance change of less than 5% for a 1000% stretch. By including
      other rubber and carbon nanotube sheath layers, we demonstrated strain sensors
      generating an 860% capacitance change and electrically powered torsional muscles
      operating reversibly by a coupled tension-to-torsion actuation mechanism. Using
      theory, we quantitatively explain the complementary effects of an increase in
      muscle length and a large positive Poisson's ratio on torsional actuation and
      electronic properties. 

PMID- 26206931
TI  - NANOCATALYSTS. Platinum-based nanocages with subnanometer-thick walls and well
      defined, controllable facets.
AB  - A cost-effective catalyst should have a high dispersion of the active atoms,
      together with a controllable surface structure for the optimization of activity,
      selectivity, or both. We fabricated nanocages by depositing a few atomic layers
      of platinum (Pt) as conformal shells on palladium (Pd) nanocrystals with well
      defined facets and then etching away the Pd templates. Density functional theory
      calculations suggest that the etching is initiated via a mechanism that involves
      the formation of vacancies through the removal of Pd atoms incorporated into the
      outermost layer during the deposition of Pt. With the use of Pd nanoscale cubes
      and octahedra as templates, we obtained Pt cubic and octahedral nanocages
      enclosed by {100} and {111} facets, respectively, which exhibited distinctive
      catalytic activities toward oxygen reduction. 

PMID- 26206932
TI  - EVOLUTION. A four-legged snake from the Early Cretaceous of Gondwana.
AB  - Snakes are a remarkably diverse and successful group today, but their
      evolutionary origins are obscure. The discovery of snakes with two legs has shed
      light on the transition from lizards to snakes, but no snake has been described
      with four limbs, and the ecology of early snakes is poorly known. We describe a
      four-limbed snake from the Early Cretaceous (Aptian) Crato Formation of Brazil.
      The snake has a serpentiform body plan with an elongate trunk, short tail, and
      large ventral scales suggesting characteristic serpentine locomotion, yet retains
      small prehensile limbs. Skull and body proportions as well as reduced neural
      spines indicate fossorial adaptation, suggesting that snakes evolved from
      burrowing rather than marine ancestors. Hooked teeth, an intramandibular joint, a
      flexible spine capable of constricting prey, and the presence of vertebrate
      remains in the guts indicate that this species preyed on vertebrates and that
      snakes made the transition to carnivory early in their history. The structure of
      the limbs suggests that they were adapted for grasping, either to seize prey or
      as claspers during mating. Together with a diverse fauna of basal snakes from the
      Cretaceous of South America, Africa, and India, this snake suggests that crown
      Serpentes originated in Gondwana. 

PMID- 26206934
TI  - NEURODEVELOPMENT. Adult cortical plasticity depends on an early postnatal
      critical period.
AB  - Development of the cerebral cortex is influenced by sensory experience during
      distinct phases of postnatal development known as critical periods. Disruption of
      experience during a critical period produces neurons that lack specificity for
      particular stimulus features, such as location in the somatosensory system.
      Synaptic plasticity is the agent by which sensory experience affects cortical
      development. Here, we describe, in mice, a developmental critical period that
      affects plasticity itself. Transient neonatal disruption of signaling via the C
      terminal domain of "disrupted in schizophrenia 1" (DISC1)-a molecule implicated
      in psychiatric disorders-resulted in a lack of long-term potentiation (LTP)
      (persistent strengthening of synapses) and experience-dependent potentiation in
      adulthood. Long-term depression (LTD) (selective weakening of specific sets of
      synapses) and reversal of LTD were present, although impaired, in adolescence and
      absent in adulthood. These changes may form the basis for the cognitive deficits
      associated with mutations in DISC1 and the delayed onset of a range of
      psychiatric symptoms in late adolescence.

PMID- 26206933
TI  - DEEP BIOSPHERE. Exploring deep microbial life in coal-bearing sediment down to
      ~2.5 km below the ocean floor.
AB  - Microbial life inhabits deeply buried marine sediments, but the extent of this
      vast ecosystem remains poorly constrained. Here we provide evidence for the
      existence of microbial communities in ~40 degrees  to 60 degrees C sediment
      associated with lignite coal beds at ~1.5 to 2.5 km below the seafloor in the
      Pacific Ocean off Japan. Microbial methanogenesis was indicated by the isotopic
      compositions of methane and carbon dioxide, biomarkers, cultivation data, and gas
      compositions. Concentrations of indigenous microbial cells below 1.5 km ranged
      from <10 to ~10(4) cells cm(-3). Peak concentrations occurred in lignite layers,
      where communities differed markedly from shallower subseafloor communities and
      instead resembled organotrophic communities in forest soils. This suggests that
      terrigenous sediments retain indigenous community members tens of millions of
      years after burial in the seabed. 

PMID- 26206935
TI  - INTRACELLULAR TRANSPORT. PI4P/phosphatidylserine countertransport at ORP5- and
      ORP8-mediated ER-plasma membrane contacts.
AB  - Lipid transfer between cell membrane bilayers at contacts between the endoplasmic
      reticulum (ER) and other membranes help to maintain membrane lipid homeostasis.
      We found that two similar ER integral membrane proteins, oxysterol-binding
      protein (OSBP)-related protein 5 (ORP5) and ORP8, tethered the ER to the plasma
      membrane (PM) via the interaction of their pleckstrin homology domains with
      phosphatidylinositol 4-phosphate (PI4P) in this membrane. Their OSBP-related
      domains (ORDs) harbored either PI4P or phosphatidylserine (PS) and exchanged
      these lipids between bilayers. Gain- and loss-of-function experiments showed that
      ORP5 and ORP8 could mediate PI4P/PS countertransport between the ER and the PM,
      thus delivering PI4P to the ER-localized PI4P phosphatase Sac1 for degradation
      and PS from the ER to the PM. This exchange helps to control plasma membrane PI4P
      levels and selectively enrich PS in the PM. 

PMID- 26206936
TI  - INTRACELLULAR TRANSPORT. Phosphatidylserine transport by ORP/Osh proteins is
      driven by phosphatidylinositol 4-phosphate.
AB  - In eukaryotic cells, phosphatidylserine (PS) is synthesized in the endoplasmic
      reticulum (ER) but is highly enriched in the plasma membrane (PM), where it
      contributes negative charge and to specific recruitment of signaling proteins.
      This distribution relies on transport mechanisms whose nature remains elusive.
      Here, we found that the PS transporter Osh6p extracted phosphatidylinositol 4
      phosphate (PI4P) and exchanged PS for PI4P between two membranes. We solved the
      crystal structure of Osh6p:PI4P complex and demonstrated that the transport of PS
      by Osh6p depends on PI4P recognition in vivo. Finally, we showed that the PI4P
      phosphatase Sac1p, by maintaining a PI4P gradient at the ER/PM interface, drove
      PS transport. Thus, PS transport by oxysterol-binding protein-related protein
      (ORP)/oxysterol-binding homology (Osh) proteins is fueled by PI4P metabolism
      through PS/PI4P exchange cycles. 

PMID- 26206938
TI  - Songwriting and science.

PMID- 26206937
TI  - AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune
      dysregulation responsive to abatacept therapy.
AB  - Mutations in the LRBA gene (encoding the lipopolysaccharide-responsive and beige
      like anchor protein) cause a syndrome of autoimmunity, lymphoproliferation, and
      humoral immune deficiency. The biological role of LRBA in immunologic disease is
      unknown. We found that patients with LRBA deficiency manifested a dramatic and
      sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte
      antigen-4)-immunoglobulin fusion drug. Clinical responses and homology of LRBA to
      proteins controlling intracellular trafficking led us to hypothesize that it
      regulates CTLA4, a potent inhibitory immune receptor. We found that LRBA
      colocalized with CTLA4 in endosomal vesicles and that LRBA deficiency or
      knockdown increased CTLA4 turnover, which resulted in reduced levels of CTLA4
      protein in FoxP3(+) regulatory and activated conventional T cells. In LRBA
      deficient cells, inhibition of lysosome degradation with chloroquine prevented
      CTLA4 loss. These findings elucidate a mechanism for CTLA4 trafficking and
      control of immune responses and suggest therapies for diseases involving the
      CTLA4 pathway. 

PMID- 26206940
TI  - Erratum for the Report "The psychological consequences of money" by K. D. Vohs,
      N. L. Mead, M. R. Goode.

PMID- 26206941
TI  - High-resolution imaging by scanning electron microscopy of semithin sections in
      correlation with light microscopy.
AB  - In this study, we introduce scanning electron microscopy (SEM) of semithin resin
      sections. In this technique, semithin sections were adhered on glass slides,
      stained with both uranyl acetate and lead citrate, and observed with a
      backscattered electron detector at a low accelerating voltage. As the specimens
      are stained in the same manner as conventional transmission electron microscopy
      (TEM), the contrast of SEM images of semithin sections was similar to TEM images
      of ultrathin sections. Using this technique, wide areas of semithin sections were
      also observed by SEM, without the obstruction of grids, which was inevitable for
      traditional TEM. This study also applied semithin section SEM to correlative
      light and electron microscopy. Correlative immunofluorescence microscopy and
      immune-SEM were performed in semithin sections of LR white resin-embedded
      specimens using a FluoroNanogold-labeled secondary antibody. Because LR white
      resin is hydrophilic and electron stable, this resin is suitable for
      immunostaining and SEM observation. Using correlative microscopy, the precise
      localization of the primary antibody was demonstrated by fluorescence microscopy
      and SEM. This method has great potential for studies examining the precise
      localization of molecules, including Golgi- and ER-associated proteins, in
      correlation with LM and SEM. 

PMID- 26206942
TI  - TWEAKing for a fight with GVHD.
AB  - In this issue of Blood, Chopra et al provide convincing evidence that tumor
      necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) ligand acting
      through its receptor, fibroblast growth factor-inducible 14 (Fn14), is crucial to
      the intestinal apoptosis seen in graft-versus-host disease (GVHD) and associated
      mortality.

PMID- 26206939
TI  - HUMAN MICROBIOTA. Small molecules from the human microbiota.
AB  - Developments in the use of genomics to guide natural product discovery and a
      recent emphasis on understanding the molecular mechanisms of microbiota-host
      interactions have converged on the discovery of small molecules from the human
      microbiome. Here, we review what is known about small molecules produced by the
      human microbiota. Numerous molecules representing each of the major metabolite
      classes have been found that have a variety of biological activities, including
      immune modulation and antibiosis. We discuss technologies that will affect how
      microbiota-derived molecules are discovered in the future and consider the
      challenges inherent in finding specific molecules that are critical for driving
      microbe-host and microbe-microbe interactions and understanding their biological
      relevance. 

PMID- 26206943
TI  - The wacky hypercoagulable state of malignancy.
AB  - In this issue of Blood, Warkentin et al describe a novel clinical syndrome of
      warfarin-associated severe venous limb ischemia occurring in a series of 10
      patients with malignancy after initiating treatment of deep venous thrombosis.
      Patients in this series also demonstrated a decline in platelet counts after
      stopping heparin, warfarin-associated supratherapeutic international normalized
      ratios (INRs), and evidence of persistent thrombin generation despite
      anticoagulation.

PMID- 26206944
TI  - Balancing bleeding in brain metastases.
AB  - In this issue of Blood, Donato et al report that treatment of venous
      thromboembolism (VTE) with anticoagulation does not increase the risk of
      intracranial hemorrhage (ICH) in patients with solid tumors metastatic to the
      brain.

PMID- 26206945
TI  - Platelet secretion paves the way.
AB  - In this issue of Blood, Sakurai et al examine the response of single platelets to
      fibrinogen- and collagen-coated microdots and show that platelets can orient
      their release of alpha-granule cargo to promote spreading beyond the dot's
      boundary.

PMID- 26206946
TI  - Warfarin pharmacogenomics and African ancestry.
AB  - In this issue of Blood, Limdi and coauthors demonstrate that racially informed
      warfarin pharmacogenetic algorithms perform better than traditional algorithms,
      which previously excluded genetic variants that are unique to patients with
      African ancestry.

PMID- 26206947
TI  - White blood cell counts and thrombosis in polycythemia vera: a subanalysis of the
      CYTO-PV study.

PMID- 26206948
TI  - Improved outcomes associated with hematopoietic stem cell transplantation for
      patients with juvenile myelomonocytic leukemia.

PMID- 26206949
TI  - Sorafenib Action in Hepatitis B Virus X-Activated Oncogenic Androgen Pathway in
      Liver through SHP-1.
AB  - BACKGROUND: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) shows
      a higher incidence in men, mainly because of hepatitis B X (HBx)-mediated
      enhancement of androgen receptor (AR) activity. We aimed to examine this pathway
      in hepatocarcinogenesis and to identify drug(s) specifically blocking this
      carcinogenic event in the liver. METHODS: HBx transgenic mice that spontaneously
      develop HCC (n = 28-34 per group) were used, either by knockout of hepatic AR or
      by castration. Efficacy of several HCC-targeted drugs in suppressing HBx-induced
      AR activity was evaluated, and cellular factors mediating suppression were
      investigated in cultured cells. Tissue specificity of the candidate drug was
      validated using mouse tissues. Data were analyzed with Chi-square and Student's t
      tests. All statistical tests were two-sided. RESULTS: The androgen pathway was
      shown to be important in early stage hepatocarcinogenesis of HBx transgenic mice.
      The tumor incidence was decreased from 80% to 32% by AR knockout (P < .001) and
      from 90% to 25% by early castration (P < .001). Sorafenib markedly inhibited the
      HBx-enhanced AR activity through activating the SHP-1 phosphatase, which
      antagonized the activation of Akt/GSK3beta and c-Src by HBx. Moreover, SHP-1
      protein level was much higher in the liver than in testis, which enabled
      sorafenib to inhibit aberrant AR activity in the HBx-expressing liver, while not
      affecting the physiological AR function in normal liver or testis. CONCLUSIONS:
      The androgen pathway may be a druggable target for the chemoprevention of HBV
      related HCC, and sorafenib might be used as a tissue- and disease-specific
      regimen for the chemoprevention of HBV-related HCC.

PMID- 26206952
TI  - Editor's Note.

PMID- 26206950
TI  - Patterns of Colorectal Cancer Care in the United States: 1990-2010.
AB  - BACKGROUND: Colorectal cancer (CRC) mortality has declined in the United States,
      in part because of advances in treatment. Few studies have evaluated the adoption
      of therapies and temporal changes in patterns of care. METHODS: Patients age 20
      years and older diagnosed with stages II/III CRC were randomly sampled from the
      population-based Surveillance, Epidemiology, and End Results (SEER) program in
      1990-1991, 1995, 2000, 2005, and 2010 (n = 7057). Therapy was obtained from
      medical records and physician verification. We described the receipt of
      chemotherapy and radiation therapy. Log-binomial regression was used to examine
      factors associated with therapy. All statistical tests were two-sided. RESULTS:
      Chemotherapy receipt among colon cancer patients increased from 1990 (stage II:
      22.5%; stage III: 56.3%) to 2005 (stage II: 32.1%; stage III: 72.4%) and declined
      slightly in 2010 (stage II: 29.3%; stage III: 66.4%). Stage III colon cancer
      patients who were older (vs <55 years, 75-79 years: risk ratio [RR] 0.81, 95%
      confidence interval [CI] = 0.71 to 0.91; >=80 years: RR = 0.37, 95% CI = 0.28 to
      0.47) or had a comorbidity score of 2 or higher (vs 0, RR = 0.56, 95% CI = 0.35
      to 0.87) received chemotherapy less often. Receipt of radiation therapy by rectal
      cancer patients increased across all years from 45.5% to 66.1%. Increasing age
      (vs <55 years, 75-79 years: RR = 0.59, 95% CI = 0.47 to 0.74; >=80 years: RR =
      0.33, 95% CI = 0.25 to 0.45) was associated with lower chemoradiation use among
      stage II/III rectal cancer patients. CONCLUSION: Our findings demonstrate
      increased adoption of chemotherapy and radiation therapy for colon and rectal
      cancer patients and differences in therapy by age, comorbidity, and diagnosis
      year. Increased receipt of these therapies in the community may further reduce
      CRC mortality.

PMID- 26206951
TI  - Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8+ T cells that
      induce GVHD without antileukemic effects.
AB  - IL-17-producing cells are important mediators of graft-versus-host disease (GVHD)
      after allogeneic stem cell transplantation (SCT). Here we demonstrate that a
      distinct CD8(+) Tc17 population develops rapidly after SCT but fails to maintain
      lineage fidelity such that they are unrecognizable in the absence of a fate
      reporter. Tc17 differentiation is dependent on alloantigen presentation by host
      dendritic cells (DCs) together with IL-6. Tc17 cells express high levels of
      multiple prototypic lineage-defining transcription factors (eg, RORgammat, T-bet)
      and cytokines (eg, IL-17A, IL-22, interferon-gamma, granulocyte macrophage colony
      stimulating factor, IL-13). Targeted depletion of Tc17 early after transplant
      protects from lethal acute GVHD; however, Tc17 cells are noncytolytic and fail to
      mediate graft-versus-leukemia (GVL) effects. Thus, the Tc17 differentiation
      program during GVHD culminates in a highly plastic, hyperinflammatory, poorly
      cytolytic effector population, which we term "inflammatory iTc17" (iTc17).
      Because iTc17 cells mediate GVHD without contributing to GVL, therapeutic
      inhibition of iTc17 development in a clinical setting represents an attractive
      approach for separating GVHD and GVL. 

PMID- 26206953
TI  - Microbial Contamination of Enteral Nutrition Mixtures in a Hyperthermal
      Environment: A Follow-Up Investigation.

PMID- 26206954
TI  - Author's Response to "Microbial Contamination of Enteral Nutrition Mixtures in a
      Hyperthermal Environment: A Follow-Up Investigation".

PMID- 26206955
TI  - Corrigendum.
AB  - Mulasi U, Kuchnia AJ, Cole AJ, Earthman CP. Bioimpedance at the bedside: current
      applications, limitations, and opportunities. Nutr Clin Pract. 2015;30:180-193.
      (Original DOI: 10.1177/0884533614568155)In this article in the April 2015 issue
      of Nutrition in Clinical Practice, the phrase "ie, the styloid process of the
      radius" was incorrectly placed in paragraph 2 under "Principles of Bioimpedance"
      on p. 181. The corrected sentence is as follows: "The most common approach for
      generating whole-body composition estimates is the standard tetrapolar
      arrangement (also termed wrist-ankle), which involves the placement of 2
      electrodes on the hand (one on the wrist between the styloid processes of the
      ulna and radius and the other just behind the metacarpals) and 2 electrodes on
      the foot (one on the ankle between the medial and lateral malleoli and the other
      just behind the metatarsals)." 

PMID- 26206956
TI  - Partnerships: pharma is closer than you think.

PMID- 26206957
TI  - Veterinary prescriptions: FVE calls for a stronger legal framework.

PMID- 26206958
TI  - APHA survey indicates that farmers are satisfied with its services.

PMID- 26206959
TI  - RCVS requests CPD records from 800 RVNs.

PMID- 26206960
TI  - Vigilance urged after H7N7 outbreak.

PMID- 26206961
TI  - Breach of code on the promotion of medicines.

PMID- 26206962
TI  - Vet retires after 37 years with the PDSA.

PMID- 26206963
TI  - 'Findings of fact' announced in adjourned disciplinary hearing.

PMID- 26206964
TI  - Trial investigates live food for broilers.

PMID- 26206965
TI  - Progress on pig health and welfare.

PMID- 26206966
TI  - 'Lancaster weekend' develops an international flavour.

PMID- 26206967
TI  - Increasingly exotic . . .

PMID- 26206968
TI  - Bovine astrovirus associated with encephalitis in cattle.

PMID- 26206969
TI  - Anaesthetising pigs.

PMID- 26206970
TI  - Proposed closure of Inverness disease surveillance centre.

PMID- 26206971
TI  - Proposed closure of Inverness disease surveillance centre.

PMID- 26206972
TI  - Granulomatous lymphadenitis caused by Nocardia species in hunted wild boar (Sus
      scrofa) in Portugal.

PMID- 26206973
TI  - Study into sterile neutrophilic-macrophagic lymphadenitis in the English springer
      spaniel.

PMID- 26206981
TI  - Born to be a VN.

PMID- 26206982
TI  - Diary of a parliamentary intern.

PMID- 26206983
TI  - Influence of propofol on oxidative-antioxidative system parameters in peripheral
      organs of rats with Parkinson disease.
AB  - Propofol (2,6-diisopropylphenol) is a popular anaesthetic agent with antioxidant
      properties. The aim of the study was to assess the oxidant-antioxidant system
      parameters of particular organs (liver, kidney, heart, and lungs) in response to
      propofol administered to rats with Parkinson's disease and to healthy ones. The
      experiment was performed using 32 Wistar rats divided into four groups (8 rats
      each). The groups were as follows: 1 control, 2 Parkinson's disease, 3 control
      with propofol, 4 Parkinson's disease with propofol. Propofol was administered at
      a dose of 60 mg/kg body weight/IP, 60 minutes before decapitation. Animals were
      sacrificed and livers, kidneys, hearts and lungs were obtained for further
      biochemical analyses. The concentration of malondialdehyde (MDA), glutathione
      reductase (GR) activity, glutathione peroxidase (GPx) activity, glutathione S
      transferase (GST) activity and catalase (CAT) activity were determined. In group
      4 compared to group 2 there was observed a significant decrease in the MDA level
      in liver (71%), kidneys (51%) and heart (12%), increased GR activity in lungs
      (48%) and heart (34%), and increased CAT activity in liver (104%). In group 3
      compared to group 1 there was a significant decrease in MDA level in kidneys
      (67%) and lungs (14%) and increased GR activity in heart (31%), liver (29%) and
      lungs (21%). Propofol can prevent or reduce damage caused by reactive oxygen
      species (ROS) by stimulating activity of antioxidative enzymes and inhibiting
      lipid peroxidation. Additionally, the response of tissues to administered
      propofol is different in Parkinson's disease and in healthy individuals. 

PMID- 26206984
TI  - [Hemoglobin adducts as biomarkers of human exposure to selected xenobiotics].
AB  - In the living and working environments more and more new substances of
      anthropogenic origin exerting toxic properties appear. Simultaneously, the
      evaluation of human exposure is assessed. For many years adducts of hemoglobin
      (Hb) have been useful markers of the exposure of humans to various xenobiotics.
      These adducts are also termed biologically effective dose biomarkers. This paper
      focuses on a review of literature, mainly from the years 2010-2014, which refers
      to the hemoglobin adducts of toxic compounds with electrophilic properties. In
      the interactions of xenobiotics with hemoglobin, groups such as thiol, amino,
      carboxyl and hydroxyl of this hemoprotein are involved. These combinations occur
      most often in the reaction of xenobiotics with an N-terminal amino group of
      valine in Hb, imidazole nitrogen of histidine and cysteine sulfhydryl beta93. Hb
      adducts are characterized by high availability, a long period of occurrence (up
      to 120 days) in the circulatory system, and high durability, and they have
      contact with all cells of the body. The measurement of hemoglobin adducts can be
      potentially used in the assessment of exposure to many xenobiotics such as
      acrylamide; substances present in tobacco smoke, e.g. benzo(alpha)pyrene and
      benzanthracene, ethylene oxide, aryl amines; and substances used on a large scale
      in industry such as glycidol and naphthalene and its derivatives. Recently the
      possibility of determination of hemoglobin adducts with estrogen metabolites has
      been postulated as indicators informing about heightened risk of breast cancer.
      Protein adducts are used as an alternative to DNA adducts for different classes
      of electrophilic substances. 

PMID- 26206985
TI  - [Copeptin - stable C-terminal fragment of pre-provasopressin as a new stress
      marker in newborns].
AB  - Stress stimuli, including diseases, disturb homeostasis of the body and enhance
      secretion of various hypothalamus, pituitary and adrenal gland hormones. One of
      the main hypothalamic hormones secreted in stress conditions is arginine
      vasopressin (AVP). Vasopressin concentration in the blood reflects the severity
      of disease and disorders of blood volume. Measurement of vasopressin is difficult
      and subjected to considerable laboratory error because of the short half-life in
      serum and its instability in withdrawn blood samples. This hormone and copeptin
      are peptides produced during the cleavage of a larger precursor polypeptide: pre
      provasopressin. Both peptides are formed in equimolar amounts. Copeptin is a more
      stable peptide, measurement of which can be performed with higher accuracy. This
      paper presents the importance of copeptin as a marker of stress, with particular
      emphasis on the neonatal period, analyzing the impact of gestational age and the
      route of delivery. Its potential application for assessing the degree of
      hydration in the adaptation period is also discussed. 

PMID- 26206986
TI  - [Phage associated polysaccharide depolymerases - characteristics and
      application].
AB  - Bacteriophages have been of interest as agents combating undesirable bacteria
      since their discovery nearly 100 years ago. Currently, intensive research is
      being conducted into two groups of phage enzymes, which cause damage to bacterial
      cells. The first group includes lysins responsible for breaking down the cell
      wall in order to release progeny phages and the second is polysaccharides
      depolymerases (PDs), which degrade capsular and structural polysaccharides,
      including exopolysaccharides (EPS) - a dominant bacterial biofilm component. PDs
      can be attached to a phage tail or present as a free form diffused to the medium,
      their production takes place constitutively or is induced by the polysaccharide
      presence. PDs belong to two groups of enzymes: hydrolases (glycanases) or
      polysaccharide lyases. These enzymes are a very heterogeneous group with regard
      to substrate specificity, the molecular weight or sensitivity bakteriofato
      physical and chemical factors. Phages producing PDs act against encapsulated
      infectious bacteria and have a great potential as a new class of anti-biofilm
      agents. Polysaccharide depolymerases depriving bacteria of the capsule, reduce
      their virulence and sensitize them to the immune system. The variety of biofilms
      forming bacteria and exopolysaccharides produced by them requires the use of
      specific phages producing DP. The problem of DP and phages specificity can be
      solved by using phage cocktails or introducing into the virus genome genes
      encoding enzymes degrading various bacterial exopolysaccharides important in the
      biofilm formation or broadening the host range. The use of DP or a DP-producing
      phage combined with other antibiofilm agents brings promising results. This
      indicates a direction for further research to develop effective methods to combat
      bacterial biofilms. Phage-borne PDs can be used for determination of the
      bacterial polysaccharides structure or efficient capsular typing. 

PMID- 26206987
TI  - [Blood groups - minuses and pluses. Do the blood group antigens protect us from
      infectious diseases?].
AB  - Human blood can be divided into groups, which is a method of blood classification
      based on the presence or absence of inherited erythrocyte surface antigens that
      can elicit immune response. According to the International Society of Blood
      Transfusion, there are 341 blood group antigens collected in 35 blood group
      systems. These antigens can be proteins, glycoproteins or glycosphingolipids, and
      function as transmembrane transporters, ion channels, adhesion molecules or
      receptors for other proteins. The majority of blood group antigens is present
      also on another types of cells. Due to their localization on the surface of
      cells, blood group antigens can act as receptors for various pathogens or their
      toxins, such as protozoa (malaria parasites), bacteria (Helicobacter pylori,
      Vibrio cholerae and Shigella dysenteriae) and viruses (Noroviruses, Parvoviruses,
      HIV). If the presence of group antigen (or its variant which arised due to
      mutation) is beneficial for the host (e.g. because pathogens are not able to bind
      to the cells), the blood group may become a selection trait, leading to its
      dissemination in the population exposed to that pathogen. There are thirteen
      blood group systems that can be related to pathogen resistance, and it seems that
      the particular influence was elicit by malaria parasites. It is generally thought
      that the high incidence of blood groups such as O in the Amazon region, Fy(a-b-)
      in Africa and Ge(-) in Papua-New Guinea is the result of selective pressure from
      malaria parasite. This review summarizes the data about relationship between
      blood groups and resistance to pathogens. 

PMID- 26206988
TI  - [Procalcitonin (PCT), contemporary indicator of infection and inflammation].
AB  - Procalcitonin is a protein synthesized during sepsis and inflammation. In these
      states, its production is stimulated by inflammatory mediators and bacterial
      toxins. Routine determination of PCT concentration is useful in the rapid
      detection and monitoring of bacterial and fungal infections. The article presents
      the latest meta-analysis and clinical reports on the use of the PCT and
      comparison of its diagnostic sensitivity and specificity with other indicators of
      inflammation and infection in both neonates and in the adult population.
      Synthesis, properties and metabolism of PCT and the available methods and
      conditions of the determination are discussed. Presented data indicate a high
      sensitivity and specificity of PCT determinations, especially in bacterial
      infection and, what is very important, short duration of the assay and the use of
      a small sample volume. Assess the dynamics of changes in the concentrations of
      PCT can provide information not only about the course of infection but also
      facilitates the decision to introduce and then to discontinue antibiotic therapy.

PMID- 26206989
TI  - [CNC proteins in physiology and pathology].
AB  - CNC proteins consist of Bach1, Bach2 and 4 homologous transcription factors:
      Nrf1, Nrf2, Nrf3 and p45NF-E2. Transcription factors belonging to this group of
      proteins play a crucial role in protection of cells against oxidative stress.
      Under physiological conditions, they remain in the cytoplasm in the inactive form
      or are degraded. However, in oxidative stress conditions, they are translocated
      to the nucleus, and bind to DNA in the ARE sequence. Consequently, there is
      transcription of genes encoding cytoprotective proteins, such as phase II
      enzymes, or low molecular weight antioxidant proteins (i.e., thioredoxin,
      ferritin, metallothionein) responsible for protecting cells from reactive oxygen
      species (ROS) action. The activity of transcriptional proteins depends directly
      on the redox state of the cell. ROS as second messenger signals, control
      inhibitors of cytoplasmic CNC proteins or potentiate the activity of kinases
      (MAPK, PKC, PI3K, PERK), leading to phosphorylation of transcription factors.
      This is conducive to translocation of these molecules into the nucleus and to
      formation of complexes that initiate the gene expression. Disorders of regulation
      of the activity of transcription factors belonging to the CNC proteins caused by
      gene mutations, epigenetic modifications or increased activity of p62, p21, or k
      Ras, B-Raf and c-Myc oncogenes, induce changes in the level of ARE-dependent gene
      expression, which can lead even to the development of carcinogenesis. On the
      other hand, Nrf transcription factors, inducing the expression of antioxidants
      and enzymes responsible for the detoxification of xenobiotics, can be considered
      as a potential target of the action of chemopreventive factors in anticancer
      therapy. 

PMID- 26206990
TI  - [The role of oxidative stress in bladder cancer].
AB  - The review of the knowledge concerning the impact of oxidative and nitrosative
      stress on signaling pathways and transcription factors involved in the formation
      of bladder cancer was prepared. In the industrialized countries, bladder cancer
      is the fourth most frequently occurring malignant tumors. Recent studies indicate
      the involvement of oxidative and nitrosative stress in the formation and
      development of this disease. Red-ox disorders are characteristic for both, the
      initiation and progression of bladder cancer. There are observed changes in the
      activity of transcription factors, such as nuclear factor NF-kB; transcription
      factors: AP-1, Nrf2 and STAT3 and hypoxia-inducible factor HIF-1alpha. In
      addition, studies indicate a role for oxidative stress in the regulation of MAPK
      cascade and its involvement in carcinogenesis consisting bladder. Examples of
      kinases belonging to the MAPK family are ERK kinases, which expression is
      proportional to the severity and malignant of bladder cancer. Nitric oxide also
      plays an important role in tumor biology. Overproduction of NO can both inhibit
      and promote tumor growth, depending on its concentration, duration of action and
      tumor microenvironment. Numerous studies show that the bladder cancer is
      characterized by an intensified production of NO. Reactive forms of nitrogen,
      similar to oxygen free radicals, could cause oxidative and nitrosative damage to
      DNA and have capacity to post-translational modification of proteins. In contrast
      to the ROS, which overproduction result from exposure to carcinogenic xenobiotic,
      nitrogen oxide in high level is produced during inflammation. Sustained iNOS
      activity therefore plays an important role in carcinogenesis associated with the
      inflammatory response, characteristic also for bladder cancer. 

PMID- 26206991
TI  - [Characterisation of selected molecular mechanisms influencing pharmacokinetics
      and pharmacodynamics of antidepressants].
AB  - Over 350 millions of people suffer from depression worldwide, and an increase in
      the incidence of the disease is expected in the coming years. Therefore, there is
      a strong need of knowing the mechanisms of development this disease and its
      effective treatment. Pharmacological therapy is an essential element of
      antidepressant therapy and its failure is a serious problem in clinical
      psychiatry. In spite of large number of available medicines, only 50% of patients
      achieved remission after single-drug treatment. Genetic factors which predispose
      to depression development and predict an outcome of its pharmacotherapy, probably
      play a substantial role in these phenomena. In spite of this, they are still not
      characterized enough and applied in practice. Therefore, the aim of this study is
      to present the current knowledge of the impact of selected genes on
      pharmacokinetics and pharmacodynamics of antidepressants by changing function
      and/or structure of encoded proteins. In the review the best known polymorphisms
      of selected genes encoding isoenzymes of cytochrome P-450, responsible for
      metabolism of popular antidepressant drugs, namely CYP2C19, CYP2D6, CYP1A2, and
      CYP3A4/5 are described. Further, 4 polymorphisms of ABCB1 gene (rs 1045642, rs
      2032582, rs 1128503 and rs 2032583) encoding glycoprotein P, which play a key
      role in transportation of large number of drugs used in treatment of depression.
      For benefit of treatment of patients with depression, it is worthy to estimate
      and to take on the board all so far known mechanisms of planning therapy. 

PMID- 26206992
TI  - [Clathrin-independent endocytosis - role in disease processes and pharmaceutical
      aspects].
AB  - Clathrin-independent endocytosis (CIE) is the process of cellular uptake of
      various particles, including pathogens, without the coat protein clathrin. It
      occurs commonly in mammalian cells and is regulated by protein-lipid composition
      of the cell membranes. Understanding of different routes of CIE allowed the
      identification of novel molecular mechanisms involved in uptake of molecules and
      cell signaling and explained their role in pathological processes. In this paper
      we characterize diseases associated with genetic defects of proteins involved in
      CIE and the relationship between expression of these proteins and pathology of
      atherosclerosis, hypercholesterolemia, diabetes and neoplasia. The role of CIE in
      bacterial, viral, fungal, and protozoal infections is also presented. In the
      second part we describe the plausible use of clathrin-independent endocytosis in
      increasing drug absorption, their penetration through biological membranes, and
      the design of specific nanocarriers for selective cell uptake. 

PMID- 26206993
TI  - [Contemporary concepts in studies on cyclic AMP and its role in the inflammatory
      reaction].
AB  - Although cyclic AMP (cAMP) was discovered more than 50 years ago, new reports of
      unknown functions of this nucleotide still appear in the literature. It is
      synthesized from adenosine triphosphate in a reaction catalysed by adenylyl
      cyclase. In mammalian cells nine membrane-associated and one soluble adenylyl
      cyclase isoforms occur. Most of them interact with Gs- or Gi-protein coupled
      receptors. The only way of cAMP degradation is the reaction of hydrolysis
      catalyzed by phosphodiesterase. In humans there are 11 families of these enzymes,
      which differ in substrate affinity, structure, place of occurrence and mechanism
      of regulation. Modulation of activity of these enzymes is an important direction
      in the search for new drugs. The effectors of cAMP are: protein kinase A (PKA),
      Epac proteins, and cAMP-dependent ion channels. In the course of the inflammatory
      response, the increase in cAMP level may lead to an increase in IL-10 expression,
      inhibition of TNF-alpha, IL-12, and MIP-1beta release, as well as to a reduction
      inthe permeability of blood vessels. In addition, cAMP regulates the process of
      phagocytosis. In the majority of cases, acting via PKA it induces cell apoptosis,
      and by activating Epac proteins it inhibits cell death. It has been shown that
      the levels of cAMP vary in different intracellular spaces due to the discretely
      positioned proteins responsible for its synthesis and breakdown. Moreover, the
      enzymatic pathway responsible for the extracellular degradation of cAMP has been
      discovered. Two transporters, ABCC4 and ABCC5, are involved in the transport of
      cAMP outside the cells. Administration of drugs modulating the level of this
      nucleotide to rodents leads to changes in its concentrations in blood and/or
      animal tissues. Progress in research on cAMP has become possible to a large
      extent due to the emergence of new analytical methods for the determination of
      its concentrations in biological material.

PMID- 26206994
TI  - [Novel adipokines: their potential role in the pathogenesis of obesity and
      metabolic disorders].
AB  - Since identification in 1994 of leptin, a hormone produced by adipocytes, adipose
      tissue has become the subject of intensive research. These studies contributed to
      the discovery that adipocytes have the ability to synthesize and secrete
      biologically active substances called "adipokines". Adipokines include a variety
      of cytokines, peptide hormones and enzymes that play a role in a wide variety of
      biological functions. For example, they are involved in the regulation of
      appetite, energy homeostasis, vascular hemostasis, blood pressure, inflammatory
      and immune processes and play a role in the metabolism of carbohydrates and fats.
      In obese patients, the secretion of adipokines is frequently abnormal. These
      changes may predispose to the development of insulin resistance, hypertension and
      inflammation. Therefore, adipokines are the subject of ongoing clinical trials.
      The family of adipokines is increasing by the newly discovered peptides. This
      paper presents the current state of knowledge about retinol binding protein 4
      (RBP-4), fasting-induced adipose factor/angiopoietin-like protein 4
      (FIAF/ANGPTL4), fibroblast growth factor-21 (FGF21), dipeptidyl peptidase-4 (DPP
      4), irisin and their potential role in the pathogenesis of metabolic disorders
      associated with obesity. The knowledge of the role of newly discovered adipokines
      may help in the treatment of metabolic syndrome. 

PMID- 26206995
TI  - [The significance of fucosylated glycoconjugates of human milk in nutrition of
      newborns and infants].
AB  - Human milk is extremely complex secretion rich in biologically active
      glycoconjugates including free oligosaccharides, glycoproteins, glycolipids, and
      glycosaminoglycans. Alpha1-2-fucosylated glycoconjugates of human milk are
      component of the innate immune system and provide an additional defense for
      infants. Participation of fucosylated glycotopes in the inhibition of infections
      caused by some bacteria and/or viruses rely on blocking of lectin-receptors of
      pathogen. Free fucosylated glycoconjugates present in milk are recognized and
      bound by the lectin-receptors of bacteria and/or viruses, and prevent pathogens
      adhesion to host epithelial cells and development of infection. So far, the
      efficacy of fucosylated glycoconjugates of human milk in the inhibition of
      adhesion has been confirmed for Escherichia coli, Campylobacter jejuni,
      Salmonella enterica, Rotaviruses, HIV, and Noroviruses. In this process the
      secretor/nonsecretor status of mother plays an important role. This is
      particularly important for the women who are nonsecretors and whose milk does not
      contain alpha1-2-fucosylated glycoconjugates and has reduced anti-microbial
      properties. Fucosylated glycoconjugates of milk are also one of the energy
      sources for physiological bacterial flora (Bifidobacterium), and have a positive
      impact on the intestinal peristalsis, and indirectly stimulate the central
      nervous system of infants. Furthermore, compared to human milk, the content of
      fucosylated glycoconjugates of cow's milk is very low and does not provide
      adequate protection. This fact is particularly important in terms of nutrition
      and should be taken into consideration when artificial mixtures based on cows'
      milk are used. The paper presents the current state of knowledge on human milk
      glycoconjugates, particularly on alpha1-2-fucosylated free oligosaccharides and
      glycoproteins, and discusses the significance of fucosylated glycoconjugates of
      human milk in the nutrition of newborns and infants.

PMID- 26206996
TI  - The role of interstitial changes in the progression of chronic kidney disease.
AB  - Interstitium - the renal tubulointerstitial compartment - is located between the
      renal tubule basement membrane and microcirculation vessels. Interstitial
      fibroblasts produce the extracellular matrix and constitute the structure's
      cellular skeleton, regulating spatial relationships between its components
      (microenvironment). The tubular epithelium and endothelium cooperate within an
      integrated microenvironment. Structural or functional impairment of the
      extracellular matrix, microcirculation vessels or tubular epithelium results in
      disturbances of tubulointerstitial compartment components. In the course of
      glomerular kidney diseases, the intrarenal RAA system becomes activated and
      inflammatory mediators are released. Interstitial inflammation and
      microcirculatory disorders develop, inducing adverse consequences, manifested
      mainly through the process of hypoxia and inflammation. Inflammation-induced
      increase in interleukin-1 (TNF-alpha) expression leads to increased
      concentrations of VEGF, ICAM-1, angiotensin II, IL-6 and IL-8. Cytokines activate
      fibroblasts, myofibroblasts and endothelial cells. Fibrosis is also triggered by
      HIF-1alpha pathway activation, resulting in vascular growth and fibroblast
      proliferation. This reaction likewise occurs through activation of NF-Kbeta, EPO,
      GLUT-1, IGF-1 and INOS. Interstitial fibrosis is one of the factors determining
      the clinical course of kidney diseases. Apart from inducing fibrosis,
      microcirculatory disorders lead to the progression of hypoxia. Angiogenesis is a
      part of the repair process accompanying fibrosis. Its determinant is the normal
      function and structure of endothelial cells manifested by their ability to
      migrate and proliferate in response to, inter alia, angiopoietins, VEGF and
      nitric oxide synthase. Administering a three-drug RAAS-inhibiting therapy to
      patients with chronic glomerulopathies improves tubular function, measured by the
      decrease in excretion of NAG and propeptide of type III procollagen fibres, and
      contributes to the improvement in microcirculation functioning. 

PMID- 26206997
TI  - [Supplementation with omega fatty acids in various diseases].
AB  - For some decades, an increase in propagation of coronary heart disease, obesity,
      diabetes, tumors and mental disorders has been observed. Consequently, new and
      effective methods of treatment of these diseases using drugs and diet supplements
      have been developed. A promising solution is the use of polyunsaturated fatty
      acids in the treatment of some diseases. These compounds have broad application
      in prevention of many diseases and are used to support standard therapies. Their
      activity is connected with participation in metabolic processes regulating
      biochemical transformations in cells and tissues. Omega-3 fatty acids regulate
      production of cytokines, increased levels of which may contribute to occurrence
      of chronic inflammatory diseases, autoaggression of the immunological system,
      arteriosclerosis or tumor development. These substances exert a beneficial effect
      on the blood system by improvement of blood circulation and nerve signal
      transmission. Omega-3 fatty acids reduce the risk of irregular heartbeat,
      stabilize arterial pressure, and restore balance in cholesterol metabolism
      disorders. They also play a key role in maintaining physical and mental
      efficiency; thus administration of these compounds for young children is of great
      importance. Nevertheless, administration of omega-3 fatty acids in the diet seems
      to be essential. The purpose of this study is to present the structure and
      sources of omega-3 and - 6 fatty acids and discuss the problems concerning
      therapeutic use of these compounds in various disorders. 

PMID- 26206998
TI  - [Stem cells of umbilical blood cord - therapeutic use].
AB  - For many years, the transplantation of hematopoietic stem cells has been used to
      treat some diseases of the hematopoietic system. For a very long time, only bone
      marrow was used as a source of hematopoietic stem cells for this method of
      treatment. However, to comply with allogeneic bone marrow transplantation, an
      antigenically compatible donor is necessary. Transplantations from unrelated
      donors are associated with increased risk of a graft-versus-host reaction,
      transplant rejection and, consequently, increased mortality. Many years ago, it
      was found that umbilical cord blood as well as bone marrow and peripheral blood
      contains hematopoietic stem cells and mesenchymal cells able to differentiate
      into different cell types and that the umbilical cord blood can be a source of
      stem cells for transplantation. Following this discovery, numerous attempts were
      made for its potential use in the treatment of hematologic diseases, metabolic
      diseases as well as regenerative medicine. Umbilical cord blood stem cells
      exhibit intermediate characteristics between embryonic and adult stem cells. They
      are distinguished from the latter by telomere length, telomerase activity, and
      lower risk of accumulation of DNA mutations or chromosomal aberrations. The only
      transplantation limitation appears to be the amount of cord blood collected,
      which on average is sufficient for transplantation in a 40-50 kg child.
      Collection of cord blood is a simple, short-lasting treatment, not causing any
      danger for a newborn or the mother. Umbilical cord blood is obtained during
      labor, and then frozen and stored at cord blood banks all over the world. 

PMID- 26206999
TI  - Extra radiation to lymph nodes reduces breast cancer recurrence, studies show.

PMID- 26207000
TI  - Lymphangiomatosis involving the mediastinum and spleen in an adult woman.

PMID- 26207001
TI  - Huge thymolipoma compressing the heart in a 20-year-old patient.

PMID- 26207002
TI  - Thyroid carcinoma showing thymus-like differentiation with tracheal invasion.
AB  - We describe a case of thyroid carcinoma showing thymus-like differentiation with
      tracheal invasion. The malignant tumor was managed by refined spiral
      tracheoplasty after tangential resection of the trachea. At 8 months after the
      surgery, computed tomography and bronchoscopy showed no tumor recurrence or
      tracheal stenosis.

PMID- 26207003
TI  - Cough-induced rib fractures.
AB  - BACKGROUND: Occasionally, patients who complain of chest pain after the onset of
      coughing are diagnosed with rib fractures. We investigated the characteristics of
      cough-induced rib fractures. METHODS: Between April 2008 and December 2013, 17
      patients were referred to our hospital with chest pain after the onset of
      coughing. Rib radiography was performed, focusing on the location of the chest
      pain. When the patient had other signs and symptoms such as fever or persistent
      cough, computed tomography of the chest was carried out. We analyzed the data
      retrospectively. RESULTS: Rib fractures were found in 14 of the 17 patients. The
      age of the patients ranged from 14 to 86 years (median 39.5 years). Ten patients
      were female and 4 were male. Three patients had chronic lung disease. There was a
      single rib fracture in 9 patients, and 5 had two or more fractures. The middle
      and lower ribs were the most commonly involved; the 10th rib was fractured most
      frequently. CONCLUSIONS: Cough-induced rib fractures occur in every age group
      regardless of the presence or absence of underlying disease. Since rib fractures
      often occur in the lower and middle ribs, rib radiography is useful for
      diagnosis.

PMID- 26207004
TI  - Primary diffuse pleural rhabdomyosarcoma in an adult patient.
AB  - Rhabdomyosarcoma is an aggressive malignant tumor of childhood, originating from
      immature cells that are destinated to form striated skeletal muscle. It usually
      arises in the head and neck or the extremities. Primary diffuse pleural
      rhabdomyosarcoma is exceptionally rare. Herein we report a case of primary
      diffuse pleural rhabdomyosarcoma in a 48-year-old man. The diagnosis was
      confirmed by percutaneous pleural biopsy. Chemotherapy (cisplatin, ifosfamide,
      adriamycin, vincristine) was initiated due to the large volume of the tumor.
      After 3 months, computed tomography of the thorax showed stable radiological
      findings.

PMID- 26207005
TI  - Operative outcomes of thoracoscopic lobectomy for non-small-cell lung cancer.
AB  - AIM: We examined the advantages of thoracoscopy over thoracotomy in terms of
      perioperative outcomes and toleration of adjuvant chemotherapy. METHODS: Between
      April 2010 and March 2013, 657 patients with non-small-cell lung cancer who
      underwent lobectomy were classified into thoracoscopy (308 patients) and
      thoracotomy (349 patients) groups and compared. RESULTS: The thoracoscopy group
      had less blood loss compared to the thoracotomy group (p < 0.001). When limiting
      the analysis to pathological stage I patients, the results were similar (p <
      0.001). In addition, the difference in blood loss between the 2 groups was
      greater in patients with severe pleural adhesions. The postoperative morbidity of
      the thoracoscopy group was significantly less than that of the thoracotomy group
      (13.3% vs. 21.2%, p < 0.001), and this result was similar when analyzing the
      pathological stage I patients (12.6% vs. 20.6%, p = 0.001). A higher percentage
      of the thoracoscopy group received both the full planned course and dose of
      adjuvant chemotherapy compared to the thoracotomy group (84.2% vs. 65.8%, p =
      0.032). CONCLUSIONS: These results indicate that totally thoracoscopic lobectomy
      is the more beneficial surgical approach with regard to the incidence of
      postoperative complications and toleration of adjuvant chemotherapy.

PMID- 26207006
TI  - Survival outcomes for oligometastasis in resected non-small cell lung cancer.
AB  - BACKGROUND: We investigated the factors associated with post-recurrence survival
      and the treatment for non-small-cell lung cancer patients with postoperative
      distant recurrence, especially oligometastasis. METHODS: We reviewed the data of
      272 patients with distant recurrence who underwent resection of non-small-cell
      lung cancer from January 2000 through December 2011. RESULTS: The type of distant
      recurrence was classified as oligometastasis (n = 76, 28%) or polymetastasis (n =
      196, 72%). Forty-seven (62%) patients with oligometastasis received local therapy
      (surgery 5, radiotherapy 9, sequential local and systemic therapy 28,
      chemoradiotherapy 5). Multivariate analysis revealed older age, non
      adenocarcinoma, shorter disease-free interval, no pulmonary metastasis, liver
      metastases, bone metastases, and polymetastasis had significant associations with
      unfavorable post-recurrence survival. Subgroup analysis of patients with
      oligometastasis showed histology and disease-free interval had a great impact on
      survival. Smoking history and histology were associated with survival in patients
      with lung oligometastasis, whereas systemic treatment and longer disease-free
      interval were related to increased post-recurrence survival in those with brain
      oligometastasis. CONCLUSIONS: This study showed that an oligometastatic state per
      se was a significant favorable factor. Optimization of personalized systemic
      treatment and adding local treatment are important in the management of patients
      with non-small-cell lung cancer and oligometastasis.

PMID- 26207007
TI  - Investment managers back greater transparency of clinical trials.

PMID- 26207008
TI  - Enhanced adhesion mechanisms between printed nano-silver electrodes and
      underlying polymer layers.
AB  - We have characterized mechanisms to improve the adhesion between printed
      electrodes prepared from silver nanoparticle inks and underlying polymer layers.
      Adhesion strength was significantly improved by sintering the inks above the
      glass transition temperature of the polymer underlayers, whereby enhanced
      adhesion was realized through interfacial fusion between the silver electrode
      layer and the underlying polymer layer. The surface energy of the underlayer was
      found to be an important factor in the improvement of adhesive strength, in that
      larger and thicker interfused regions between layers were observed for
      underlayers that had higher surface energies. 

PMID- 26207009
TI  - Screening for Peripheral Arterial Disease Using the Ankle-Brachial Index in
      Diabetic and Other High-Risk Patients: Pros and Cons.

PMID- 26207010
TI  - Abstract book of the 30th ESHRE Annual Meeting, Munich, Germany, 29 June - 2 July
      2014.

PMID- 26207011
TI  - The prevalence of late-life mental disorders in New Zealand and Australia is
      still unknown.

PMID- 26207012
TI  - Abstract book of the 31st ESHRE Annual Meeting, Lisbon, Portugal, 14-17 June
      2015.

PMID- 26207013
TI  - Sensing using plasmonic nanostructures and nanoparticles.
AB  - Nanoparticles are widely used in various fields of science and technology as well
      as in everyday life. In particular, gold and silver nanoparticles display unique
      optical properties that render them extremely attractive for various
      applications. In this review, we focus on the use of noble metal nanoparticles as
      plasmonic nanosensors with extremely high sensitivity, even reaching single
      molecule detection. Sensors based on plasmon resonance shifts, as well as the use
      of surface-enhanced Raman scattering and surface-enhanced fluorescence, will be
      considered in this work. 

PMID- 26207014
TI  - Light emission, light detection and strain sensing with nanocrystalline graphene.
AB  - Graphene is of increasing interest for optoelectronic applications exploiting
      light detection, light emission and light modulation. Intrinsically, the light
      matter interaction in graphene is of a broadband type. However, by integrating
      graphene into optical micro-cavities narrow-band light emitters and detectors
      have also been demonstrated. These devices benefit from the transparency,
      conductivity and processability of the atomically thin material. To this end, we
      explore in this work the feasibility of replacing graphene with nanocrystalline
      graphene, a material which can be grown on dielectric surfaces without catalyst
      by graphitization of polymeric films. We have studied the formation of
      nanocrystalline graphene on various substrates and under different graphitization
      conditions. The samples were characterized by resistance, optical transmission,
      Raman and x-ray photoelectron spectroscopy, atomic force microscopy and electron
      microscopy measurements. The conducting and transparent wafer-scale material with
      nanometer grain size was also patterned and integrated into devices for studying
      light-matter interaction. The measurements show that nanocrystalline graphene can
      be exploited as an incandescent emitter and bolometric detector similar to
      crystalline graphene. Moreover the material exhibits piezoresistive behavior
      which makes nanocrystalline graphene interesting for transparent strain sensors. 

PMID- 26207015
TI  - Bias assisted scanning probe microscopy direct write lithography enables local
      oxygen enrichment of lanthanum cuprates thin films.
AB  - Scanning probe bias techniques have been used as a method to locally dope thin
      epitaxial films of La(2)CuO(4) (LCO) fabricated by pulsed laser deposition. The
      local electrochemical oxidation of LCO very efficiently introduces interstitial
      oxygen defects in the thin film. Details on the influence of the tip voltage bias
      and environmental conditions on the surface morphology have been investigated.
      The results show that a local uptake of oxygen occurs in the oxidized films.

PMID- 26207016
TI  - The effects of chemical and physical factors on mammalian embryo culture and
      their importance for the practice of assisted human reproduction.
AB  - BACKGROUND: Although laboratory procedures, along with culture media
      formulations, have improved over the past two decades, the issue remains that
      human IVF is performed in vitro (literally 'in glass'). METHODS: Using PubMed,
      electronic searches were performed using keywords from a list of chemical and
      physical factors with no limits placed on time. Examples of keywords include
      oxygen, ammonium, volatile organics, temperature, pH, oil overlays and incubation
      volume/embryo density. Available clinical and scientific evidence surrounding
      physical and chemical factors have been assessed and presented here. RESULTS AND
      CONCLUSIONS: Development of the embryo outside the body means that it is
      constantly exposed to stresses that it would not experience in vivo. Sources of
      stress on the human embryo include identified factors such as pH and temperature
      shifts, exposure to atmospheric (20%) oxygen and the build-up of toxins in the
      media due to the static nature of culture. However, there are other sources of
      stress not typically considered, such as the act of pipetting itself, or the
      release of organic compounds from the very tissue culture ware upon which the
      embryo develops. Further, when more than one stress is present in the laboratory,
      there is evidence that negative synergies can result, culminating in significant
      trauma to the developing embryo. It is evident that embryos are sensitive to both
      chemical and physical signals within their microenvironment, and that these
      factors play a significant role in influencing development and events post
      transfer. From the viewpoint of assisted human reproduction, a major concern with
      chemical and physical factors lies in their adverse effects on the viability of
      embryos, and their long-term effects on the fetus, even as a result of a
      relatively brief exposure. This review presents data on the adverse effects of
      chemical and physical factors on mammalian embryos and the importance of
      identifying, and thereby minimizing, them in the practice of human IVF. Hence,
      optimizing the in vitro environment involves far more than improving culture
      media formulations.

PMID- 26207017
TI  - Hybrid NiS/CoO mesoporous nanosheet arrays on Ni foam for high-rate
      supercapacitors.
AB  - A new hybrid of NiS/CoO porous nanosheets was synthesized on Ni foam by one-step
      electrodeposition method and used as an electrode for high-performance
      pseudocapacitance. The as-synthesized NiS/CoO porous nanosheets hybrid shows a
      high specific capacitance of 1054 F g(-1) at a high current density of 6 A g(-1),
      a good rate capability even at high current density (760 F g(-1) at 20 A g(-1))
      and a good long-term cycling stability (91.7% of the maximum specific capacitance
      after 3000 cycles). These excellent properties can be mainly attributed to the
      unique hierarchical porous structure with large surface area and interspaces
      which facilitate charge transfer and redox reaction. The enhancement in the
      interface contact between active material and substrate results in excellent
      conductivity of the electrode and a strong synergistic effect of NiS and CoO as
      individual constituents contributed to high capacitance of the hybrid electrode. 

PMID- 26207018
TI  - In situ capping for size control of monochalcogenide (ZnS, CdS and SnS)
      nanocrystals produced by anaerobic metal-reducing bacteria.
AB  - Metal monochalcogenide quantum dot nanocrystals of ZnS, CdS and SnS were prepared
      by anaerobic, metal-reducing bacteria using in situ capping by oleic acid or
      oleylamine. The capping agent preferentially adsorbs on the surface of the
      nanocrystal, suppressing the growth process in the early stages, thus leading to
      production of nanocrystals with a diameter of less than 5 nm. 

PMID- 26207019
TI  - Peripherally Inserted Central Catheter-Related Vein Thrombosis in Patients With
      Lung Cancer.
AB  - BACKGROUND: Peripherally inserted central venous catheters (PICCs) are widely
      used in patients with cancer. Catheter usage is one of the risk factors for
      venous thromboembolism. We aimed to scrutinize the incidence and risk factors for
      PICC-related upper extremity venous thrombosis (UEVT) in patients with lung
      cancer receiving chemotherapy. PATIENTS AND METHODS: We performed a retrospective
      cohort study of patients with lung cancer with PICC insertion undergoing
      chemotherapy. Symptomatic PICC-UEVT was diagnosed by ultrasound. The relationship
      between chemotherapeutic agent exposure and PICC-UEVT was evaluated. Patient-,
      catheter-, and insertion-related factors were analyzed in univariable and
      multivariable logistic regression to identify significant independent risk
      factors for PICC-UEVT in patients with lung cancer. RESULTS: A total of 328
      patients with lung cancer having PICC undergoing chemotherapy were included, for
      a total of 34 895 catheter days. Seventeen (5.2%) patients developed PICC-related
      UEVT, with an incidence of 0.49 per 1000 catheter days. In multivariable logistic
      analysis, advanced disease was shown to be a significant risk factor for PICC
      UEVT (odds ratio [OR]: 4.9; 95% confidence interval [CI]: 1.4-16.7; P = .011).
      Patients treated with etoposide had a higher risk of PICC-related UEVT (OR: 3.6;
      95% CI: 1.1-12.1; P = .042). Patients were followed up after PICC removal for a
      median duration of 246 days. None of the patients developed pulmonary embolism.
      CONCLUSION: Patients with lung cancer harboring an advanced disease or treating
      with etoposide were at higher risk of PICC-UEVT.

PMID- 26207020
TI  - Four-Group Classification Based on Fibrinogen Level and Fibrin Polymerization
      Associated With Postoperative Bleeding in Cardiac Surgery.
AB  - Fibrinogen and fibrin formation have a key role in perioperative hemostasis. The
      aim of this study is to examine the association of postoperative hemostasis with
      a combined evaluation of the fibrinogen level and fibrin polymerization in
      cardiac surgery. We retrospectively classified 215 consecutive cardiac surgery
      patients into 4 groups (Fuji-san classification) that were divided by fibrinogen
      level <150 mg/dL (ie, hypofibrinogenemia) and fibrinogen thromboelastometry value
      at 10 minutes with rotational thromboelastometry <6 mm (ie, low fibrin
      polymerization) at the warming of cardiopulmonary bypass. Four groups resulted;
      group I, the acceptable range (n = 85); group II, only hypofibrinogenemia (<150
      mg/dL, >=6 mm, n = 63); group III, hypofibrinogenemia and low fibrin
      polymerization (<150 mg/dL, <6 mm, n = 60); and group IV, only low fibrin
      polymerization (>=150 mg/dL, <6 mm, n = 7). The risk of chest tube drainage
      volume greater than 500 mL within the first 24 hours after surgery (with group I
      as the reference) was increased in group II (odds ratio [OR], 3.3; 95% confidence
      interval [CI], 1.5-7.4; P < .01) and group III (OR, 8.5; 95% CI, 3.5-21.7; P <
      .01), and the risk greater than 1000 mL (with group I as the reference) was
      increased in group III (OR, 4.0; 95% CI, 1.1-17.3; P = .03) and group IV (OR,
      23.1; 95% CI, 3.2-201.0; P < .01). Intraoperative blood transfusions were
      decreased by 24.5%, after stratifying the starting amount of fresh frozen plasma
      by the 4-group classification in the recent consecutive 65 (30.2%) patients (P <
      .01). The 4-group classification is associated with postoperative bleeding and
      may improve the quality of perioperative blood transfusion in cardiac surgery. 

PMID- 26207021
TI  - Fibrinolytic Dysregulation in Total Joint Arthroplasty Patients: Potential
      Clinical Implications.
AB  - BACKGROUND: The alterations of the fibrinolytic components in osteoarthritic
      joint disease and their postsurgical modulation are not clearly understood.
      Preexisting hemostatic dysfunction may lead to both thrombotic and bleeding
      events in these patients. AIM: To profile fibrinolytic parameters in patients
      undergoing total joint arthroplasty prior to and on postoperative day 1. METHODS:
      A total of 98 total joint arthroplasty patients were included in this study.
      Blood samples were drawn preoperatively and on postoperative day 1 status
      posttotal knee or total hip arthroplasty surgery. d-Dimer, plasminogen activator
      inhibitor 1 (PAI-1), and tissue plasminogen activator (tPA) were measured using
      commercially available enzyme-linked immunosorbent assay kits. Antiplasmin
      activity was measured by using a functional method. RESULTS: Preoperative PAI-1,
      d-dimer, and tPA levels were significantly higher in arthroplasty patients
      compared to healthy controls. Preoperative antiplasmin level was lower than
      controls. Postoperative levels of PAI-1 and d-dimer were increased compared to
      preoperative values. Postoperative antiplasmin values were lower than
      preoperative levels. Changes in tPA was not significant. There was no correlation
      between preoperative PAI-1 and d-dimer levels. Pre- and postoperative percentage
      changes in each individual were calculated for PAI-1, d-dimer, tPA, and
      antiplasmin. There was a positive correlation between d-dimer and PAI-1. Negative
      correlations between antiplasmin and d-dimer and between antiplasmin and PAI-1
      were noted. CONCLUSION: These results confirm the perturbation in the
      fibrinolytic system of patients undergoing total joint arthroplasty surgery.
      Surgical intervention may also enhance the observed changes. The alterations in
      the fibrinolytic system may lead to the observed hemostatic complications such as
      bleeding, hematoma formation, or potential need for blood transfusion.

PMID- 26207022
TI  - Headache and peak oxygen uptake: The HUNT3 study.
AB  - BACKGROUND: Evidence on the association between headache and physical fitness is
      conflicting. The aim of this population-based study was to examine the
      relationship between peak oxygen uptake (VO2peak) and headache, including
      migraine and tension-type headache (TTH). METHODS: In the third Nord-Trondelag
      Health study (HUNT3), VO2peak was measured by ergospirometry in a sample of 4631
      healthy adult participants. Of these, 3899 (54% women) also answered headache
      questions. The cross-sectional association between headache and VO2peak was
      evaluated by logistic regression using a categorical approach based on quintiles.
      Scores in the upper quintile were used as reference. RESULTS: Participants age 20
      50 years had significant trends of increasing prevalence of any headache (
      ITALIC! p < 0.001), migraine ( ITALIC! p < 0.001), TTH ( ITALIC! p = 0.002) and
      unclassified headache ( ITALIC! p = 0.027) with lower VO2peak. The highest
      prevalence odds ratios (ORs) were found in those with VO2peak in the lower
      quintile: For any headache the OR was 2.3 (95% confidence interval (1.6-3.3), for
      TTH 1.8 (1.2-2.8), for unclassified headache 1.9 (1.1-3.8), and for migraine 3.7
      (2.1-6.6). Similar results were also found among those who reported physical
      activity levels in accordance with current recommendations of the American
      College of Sports Medicine but nevertheless had low VO2peak. Being in the lowest
      VO2peak quintile was also strongly associated with migraine aggravated by
      physical activity (OR 4.1, 2.1-8.1). No significant association was found between
      VO2peak and headache for those 50 years or older. CONCLUSIONS: In this large
      cross-sectional study, an inverse relationship was found between VO2peak and
      headache for adults younger than 50 years of age.

PMID- 26207023
TI  - Effect and Mechanism of Virechana Karma (Therapeutic Purgation) Over Fructose
      Induced Metabolic Syndrome: An Experimental Study.
AB  - BACKGROUND: Panchakarma (biopurification methods) is one of the modes of ayurveda
      to treat disorders of the body. Virechana karma (therapeutic purgation), one
      among the Panchakarma, is a purification process that is commonly used to treat
      metabolic disorders like obesity and diabetes mellitus. Hence this study was
      planned to provide evidence through animal experiments. METHODS: Albino rats were
      subject to Virechana karma (therapeutic purgation) to evaluate the influence of
      therapy and its mechanism over fructose-induced metabolic syndrome. RESULTS:
      Results show that Virechana is effective in the management of the metabolic
      syndrome with decrease in the fecal fat content, fasting blood glucose, serum
      triglyceride, and reduced fatty changes in liver, heart, and kidney in comparison
      with the positive control group. CONCLUSION: Experimental evaluation showed
      decrease in fatty acid in the storage like liver, kidney, heart, and muscle
      adipose tissue can indirectly increase the insulin sensitivity in insulin
      receptor present at skeletal muscles.

PMID- 26207024
TI  - Europe's governments must implement standardised tobacco packaging now.

PMID- 26207025
TI  - The Europe we want-a Transatlantic Health and Wellbeing Partnership?

PMID- 26207026
TI  - How ehealth can help with Europe's chronic diseases epidemic.

PMID- 26207027
TI  - TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone
      loss.
AB  - Accumulating evidence points to the importance of the innate immune system in
      inflammation-induced bone loss in infectious and autoimmune diseases. TLRs are
      well known for being activated by ligands expressed by bacteria, viruses, and
      fungi. Recent findings indicate that also endogenous ligands in inflammatory
      processes are important, one being a TLR5 agonist present in synovial fluid from
      patients with rheumatoid arthritis (RA). We found that activation of TLR5 by its
      specific ligand, flagellin, caused robust osteoclast formation and bone loss in
      cultured mouse neonatal parietal bones dependent on increased receptor activator
      of NF-kappaB ligand (RANKL):osteoprotegerin ratio, with half-maximal stimulation
      at 0.01 MUg/ml. Flagellin enhanced Rankl mRNA in isolated osteoblasts by a
      myeloid differentiation primary response gene 88 and NF-kappaB-dependent
      mechanism. Injection of flagellin locally over skull bones in 5-wk-old mice
      resulted in increased mRNA expression of Rankl and osteoclastic genes, robust
      osteoclast formation, and bone loss. The effects in vitro and in vivo were absent
      in Tlr5(-/-) mice. These data show that TLR5 is a novel activator of RANKL and
      osteoclast formation and, therefore, a potential key factor in inflammation
      induced bone erosions in diseases like RA, reactive arthritis, and periodontitis.
      TLR5 might be a promising novel treatment target for prevention of inflammatory
      bone loss.

PMID- 26207028
TI  - Transient receptor potential vanilloid 2-mediated shear-stress responses in C2C12
      myoblasts are regulated by serum and extracellular matrix.
AB  - The developmental sensitivity of skeletal muscle to mechanical forces is
      unparalleled in other tissues. Calcium entry via reputedly mechanosensitive
      transient receptor potential (TRP) channel classes has been shown to play an
      essential role in both the early proliferative stage and subsequent
      differentiation of skeletal muscle myoblasts, particularly TRP canonical (TRPC) 1
      and TRP vanilloid (TRPV) 2. Here we show that C2C12 murine myoblasts respond to
      fluid flow-induced shear stress with increments in cytosolic calcium that are
      largely initiated by the mechanosensitive opening of TRPV2 channels. Response to
      fluid flow was augmented by growth in low extracellular serum concentration (5
      vs. 20% fetal bovine serum) by greater than 9-fold and at 18 h in culture,
      coincident with the greatest TRPV2 channel expression under identical conditions
      (P < 0.02). Fluid flow responses were also enhanced by substrate
      functionalization with laminin, rather than with fibronectin, agreeing with
      previous findings that the gating of TRPV2 is facilitated by laminin. Fluid flow
      induced calcium increments were blocked by ruthenium red (27%) and SKF-96365
      (38%), whereas they were unaltered by 2-aminoethoxydiphenyl borate, further
      corroborating that TRPV2 channels play a predominant role in fluid flow
      mechanosensitivity over that of TRPC1 and TRP melastatin (TRPM) 7.

PMID- 26207029
TI  - Appropriate expression of Ube2C and Ube2S controls the progression of the first
      meiotic division.
AB  - Timely degradation of protein regulators of the cell cycle is essential for the
      completion of cell division. This degradation is promoted by the E3 anaphase
      promoting complex/cyclosome (APC/C) and mediated by the E2 ubiquitin-conjugating
      enzymes (Ube2s). Unlike the ample information gathered regarding the meiotic E3
      APC/C, the E2s participating in this cell division have never been studied. We
      identified Ube2C, -S, and -D3 as the E2 enzymes that regulate APC/C activity
      during meiosis of mouse oocytes. Their depletion reduces the levels of the first
      meiotic cytokinesis by 50%, and their overexpression doubles and accelerates its
      completion (50% as compared with 4% at 11 h). We also demonstrated that these E2s
      take part in ensuring appropriate spindle formation. It is noteworthy that high
      levels of Ube2C bring about the resumption of the first meiotic division,
      regardless of the formation of the spindle, overriding the spindle assembly
      checkpoint. Thus, alongside their canonical function in protein degradation,
      Ube2C and -S also control the extrusion of the first polar body. Overall, our
      study characterizes new regulators and unveils the novel roles they play during
      the meiotic division. These findings shed light on faithful chromosome
      segregation in oocytes and may contribute to better understanding of aneuploidy
      and its consequent genetic malformations.

PMID- 26207032
TI  - beta-Cell Identity in Type 2 Diabetes: Lost or Found?

PMID- 26207033
TI  - Set Phages to Stun: Reducing the Virulence of Staphylococcus aureus in Diabetic
      Foot Ulcers.

PMID- 26207031
TI  - Uncomplicating the Macrovascular Complications of Diabetes: The 2014 Edwin
      Bierman Award Lecture.
AB  - The risk of cardiovascular events in humans increases in the presence of type 1
      or type 2 diabetes mellitus, in large part due to exacerbated atherosclerosis.
      Genetically engineered mouse models have begun to elucidate cellular and
      molecular mechanisms responsible for diabetes-exacerbated atherosclerosis.
      Research on these mouse models has revealed that diabetes independently
      accelerates initiation and progression of lesions of atherosclerosis and also
      impairs the regression of lesions following aggressive lipid lowering. Myeloid
      cell activation in combination with proatherogenic changes allowing for increased
      monocyte recruitment into arteries of diabetic mice has emerged as an important
      mediator of the effects of diabetes on the three stages of atherosclerosis. The
      effects of diabetes on atherosclerosis appear to be dependent on an interplay
      between glucose and lipids, as well as other factors, and result in increased
      recruitment of monocytes into both progressing and regressing lesions of
      atherosclerosis. Importantly, some of the mechanisms revealed by mouse models are
      now being studied in human subjects. This Perspective highlights new mechanistic
      findings based on mouse models of diabetes-exacerbated atherosclerosis and
      discusses the relevance to humans and areas in which more research is urgently
      needed in order to lessen the burden of macrovascular complications of type 1 and
      type 2 diabetes mellitus. 

PMID- 26207034
TI  - Enhancing Stem Cell Mobility: New Hope for Treatment of Cardiovascular
      Complications in Patients With Diabetes?

PMID- 26207035
TI  - Differential Modulation of Cardiac Sympathetic Neural Control and beta
      Adrenoceptor-G Protein Signaling Cascade in Rats With Type 1 and Type 2 Diabetes.

PMID- 26207036
TI  - The VASP Road to NAFLD: A Macrophage Detour.

PMID- 26207037
TI  - Acute Adaptation of Energy Expenditure Predicts Diet-Induced Weight Loss:
      Revisiting the Thrifty Phenotype.

PMID- 26207038
TI  - Fat Prospects for Healing Cutaneous Wounds: New Activities Under the Sheets.

PMID- 26207039
TI  - Causal or Noncausal Relationship of Uric Acid With Diabetes.

PMID- 26207040
TI  - Erratum. Increased Insulin Sensitivity and Hypoinsulinemia in APS Knockout Mice.
      Diabetes 2003;52:2657-2665.

PMID- 26207042
TI  - Comment on Sofi et al. pH of Drinking Water Influences the Composition of Gut
      Microbiome and Type 1 Diabetes Incidence. Diabetes 2014;63:632-644.

PMID- 26207043
TI  - Response to Comment on Sofi et al. pH of Drinking Water Influences the
      Composition of Gut Microbiome and Type 1 Diabetes Incidence. Diabetes 2014;63:632
      644.

PMID- 26207044
TI  - The human salivary microbiome exhibits temporal stability in bacterial diversity.
AB  - The temporal variability of the human microbiome may be an important factor in
      determining its relationship with health and disease. In this study, the saliva
      of 40 participants was collected every 2 months over a one-year period to
      determine the temporal variability of the human salivary microbiome. Salivary pH
      and 16S rRNA gene copy number were measured for all participants, with the
      microbiome of 10 participants assessed through 16S rRNA amplicon sequencing. In
      February 2013, 16S rRNA gene copy number was significantly (P < 0.001) higher,
      with individual changes between time points significant (P = 0.003). Salivary pH
      levels were significantly (P < 0.001) higher in December 2012 than in October
      2012 and February 2013, with significant (P < 0.001) individual variations seen
      throughout. Bacterial alpha-diversity showed significant differences between
      participants (P < 0.001), but not sampling periods (P = 0.801), and a significant
      positive correlation with salivary pH (R(2) = 7.8%; P = 0.019). At the phylum
      level, significant differences were evident between participants in the
      Actinobacteria (P < 0.001), Bacteroidetes (P < 0.001), Firmicutes (P = 0.008),
      Fusobacteria (P < 0.001), Proteobacteria (P < 0.001), Synergistetes (P < 0.001)
      and Spirochaetes (P = 0.003) phyla. This study charted the temporal variability
      of the salivary microbiome, suggesting that bacterial diversity is stable, but
      that 16S rRNA gene copy number may be subject to seasonal flux. 

PMID- 26207046
TI  - Assessing the effects of salmon farming seabed enrichment using bacterial
      community diversity and high-throughput sequencing.
AB  - Aquaculture is an extremely valuable and rapidly expanding sector of the seafood
      industry. The sediment below active aquaculture farms receives inputs of organic
      matter from uneaten food and faecal material and this has led to concerns related
      to environmental sustainability. The impacts of organic enrichment on
      macrobenthic infauna are well characterized; however, much less is known about
      effect on bacterial communities. In this study, sediment, macrobenthic infauna
      samples and environmental data were collected along an enrichment gradient
      radiating out from a Chinook salmon (Oncorhynchus tshawytscha) farm (Marlborough
      Sounds; New Zealand). DNA and RNA were extracted and 16S rRNA metabarcodes from
      bacterial communities characterized using high-throughput sequencing.
      Desulfobacterales dominated at the cage (DNA and RNA), and at sites 50 m (DNA and
      RNA) and 150 m (RNA) from the farm. In contrast, unclassified bacteria from the
      class Gammaproteobacteria were the most abundant taxa at control sites (625 and
      4000 m). Pronounced differences among DNA and RNA samples occurred at the cage
      site where Desulfobacterales abundance was markedly higher in RNA samples. There
      were strong correlations between shifts in bacterial communities and total
      organic matter and redox. This suggests that bacterial composition is strongly
      influenced by organic enrichment, a trait that may make them useful for assessing
      impacts associated with aquaculture farms. 

PMID- 26207047
TI  - Detection of the macrolide-lincosamide-streptogramin B resistance gene erm(44)
      and a novel erm(44) variant in staphylococci from aquatic environments.
AB  - Resistance to macrolides, lincosamides and streptogramin B antibiotics (MLSB) is
      not restricted to staphylococci from clinical samples but can also be present in
      staphylococci from the aquatic environment. Two coagulase-negative staphylococci
      Staphylococcus xylosus and S. saprophyticus were obtained from sewage and
      receiving river water samples and were investigated for the genetic basis of
      inducible MLSB resistance by whole-genome sequencing. Two rRNA methylases encoded
      by erm(44) and a novel erm(44) variant were identified, which had only 84% amino
      acid identity. While fragments of phage DNA were found in the vicinity of the
      erm(44) gene of S. xylosus, no relics of mobile genetic elements were detected in
      the sequences flanking the erm(44) variant gene in the S. saprophyticus strain.
      The functionality of the erm genes was confirmed by cloning and transformation
      experiments. Based on the obtained sequences, specific PCR assays for both erm
      genes were developed and used to identify erm(44) in another 7 S. xylosus and 17
      S. saprophyticus isolates from aquatic environments. 

PMID- 26207045
TI  - Complex coupled metabolic and prokaryotic community responses to increasing
      temperatures in anaerobic marine sediments: critical temperatures and substrate
      changes.
AB  - The impact of temperature (0-80 degrees C) on anaerobic biogeochemical processes
      and prokaryotic communities in marine sediments (tidal flat) was investigated in
      slurries for up to 100 days. Temperature had a non-linear effect on
      biogeochemistry and prokaryotes with rapid changes over small temperature
      intervals. Some activities (e.g. methanogenesis) had multiple 'windows' within a
      large temperature range (~10 to 80 degrees C). Others, including acetate
      oxidation, had maximum activities within a temperature zone, which varied with
      electron acceptor [metal oxide (up to ~34 degrees C) and sulphate (up to ~50
      degrees C)]. Substrates for sulphate reduction changed from predominantly acetate
      below, and H2 above, a 43 degrees C critical temperature, along with changes in
      activation energies and types of sulphate-reducing Bacteria. Above ~43 degrees C,
      methylamine metabolism ceased with changes in methanogen types and increased
      acetate concentrations (>1 mM). Abundances of uncultured Archaea, characteristic
      of deep marine sediments (e.g. MBGD Euryarchaeota, 'Bathyarchaeota') changed,
      indicating their possible metabolic activity and temperature range. Bacterial
      cell numbers were consistently higher than archaeal cells and both decreased
      above ~15 degrees C. Substrate addition stimulated activities, widened some
      activity temperature ranges (methanogenesis) and increased bacterial (*10) more
      than archaeal cell numbers. Hence, additional organic matter input from climate
      related eutrophication may amplify the impact of temperature increases on
      sedimentary biogeochemistry. 

PMID- 26207048
TI  - A novel Vibrio beta-glucosidase (LamN) that hydrolyzes the algal storage
      polysaccharide laminarin.
AB  - The metabolic versatility, tractability and rapid growth potential of the Vibrio
      spp. have made them increasingly attractive systems for investigating carbon
      cycling in the marine environment. In this study, an in silico subtractive
      proteomic strategy was used to identify a novel 101 kDa GH3 family beta
      glucosidase (LamN) that was found in bioluminescent Vibrio campbellii strains
      capable of utilizing the algal storage glucan laminarin. A heterologous
      overexpression system verified the sequence-predicted function of LamN as it
      enabled the growth of Escherichia coli on laminarin as a sole carbon source.
      Quantitative reverse transcription PCR analyses revealed that V. campbellii grown
      on laminarin demonstrated a 4- to 314-fold induction of lamN gene expression when
      compared to the same strains grown on glucose or glycerol. Corresponding tandem
      mass spectrometric analyses detected LamN protein expression only in cells grown
      on laminarin. Heterologous expression, purification and biochemical
      characterization identified LamN as a heat stable laminarinase with beta-1,3,
      beta-1,4 and beta-1,6 glucosidase activity. Collectively, these data identify an
      enzyme that may allow V. campbellii to exploit some of the most abundant
      polysaccharides associated with deteriorating phytoplankton blooms and provide
      support for the potential involvement of V. campbellii in the formation of
      bioluminescent milky seas. 

PMID- 26207050
TI  - Evidence Tips the Scale Toward Screening for Hyperglycemia.

PMID- 26207052
TI  - Minimizing Hypoglycemia in Diabetes.
AB  - Hypoglycemia caused by treatment with a sulfonylurea, a glinide, or insulin
      coupled with compromised defenses against the resulting falling plasma glucose
      concentrations is a problem for many people with diabetes. It is often recurrent,
      causes significant morbidity and occasional mortality, limits maintenance of
      euglycemia, and impairs physiological and behavioral defenses against subsequent
      hypoglycemia. Minimizing hypoglycemia includes acknowledging the problem;
      considering each risk factor; and applying the principles of intensive glycemic
      therapy, including drug selection and selective application of diabetes treatment
      technologies. For diabetes health-care providers treating most people with
      diabetes who are at risk for or are suffering from iatrogenic hypoglycemia, these
      principles include selecting appropriate individualized glycemic goals and
      providing structured patient education to reduce the incidence of hypoglycemia.
      This is typically combined with short-term scrupulous avoidance of hypoglycemia,
      which often will reverse impaired awareness of hypoglycemia. Clearly, the risk of
      hypoglycemia is modifiable. 

PMID- 26207051
TI  - Obesity and Gestational Diabetes Mellitus Pathways for Programming in Mouse,
      Monkey, and Man-Where Do We Go Next? The 2014 Norbert Freinkel Award Lecture.
AB  - Obesity and gestational diabetes mellitus continue to increase worldwide and span
      the spectrum of age, race, ethnicity, and socioeconomic status. Alarmingly, 1 in
      10 infants and toddlers is obese, and 1 in 5 youths is both obese and at risk for
      metabolic syndrome prior to puberty. The mechanisms underlying how poor maternal
      health imparts risk for future metabolic disease in the offspring are beginning
      to emerge in deeply phenotyped human and nonhuman primate models. Maternal diet
      and obesity impact fuels, hormones, and inflammation with powerful effects on
      fetal metabolic systems. These are accompanied by persistent changes in the
      infant microbiome and epigenome and in offspring behavior. These results suggest
      that gestational and lactational dietary exposures are driving health risks in
      the next generation. Whether maternal diet can prevent changes in the womb to
      alter infant life-course disease risk is still unknown. Controlled, mechanistic
      studies to identify interventions are sorely needed for a healthier next
      generation. 

PMID- 26207053
TI  - Interventions That Restore Awareness of Hypoglycemia in Adults With Type 1
      Diabetes: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: Impaired awareness of hypoglycemia (IAH) increases the risk of severe
      hypoglycemia (SH) sixfold and affects 30% of adults with type 1 diabetes (T1D).
      This systematic review and meta-analysis looks at the educational, technological,
      and pharmacological interventions aimed at restoring hypoglycemia awareness (HA)
      in adults with T1D. RESEARCH DESIGN AND METHODS: We searched The Cochrane
      Library, MEDLINE, Embase, Science Citation Index Expanded, Social Sciences
      Citation Index, PsycINFO, and CINAHL from inception until 1 October 2014.
      Included studies described HA status at baseline. Outcome measures were SH rates,
      change in HA, counterregulatory hormone responses, and glycemic control. RESULTS:
      Forty-three studies (18 randomized controlled trials, 25 before-and-after
      studies) met the inclusion criteria, comprising 27 educational, 11 technological,
      and 5 pharmacological interventions. Educational interventions included
      structured diabetes education on flexible insulin therapy, including
      psychotherapeutic and behavioral techniques. These were able to reduce SH and
      improve glycemic control, with greater benefit from the latter two techniques in
      improving IAH. Technological interventions (insulin pump therapy, continuous
      glucose monitoring, and sensor-augmented pump) reduced SH, improved glycemic
      control, and restored awareness when used in combination with structured
      education and frequent contact. Pharmacological studies included four insulin
      studies and one noninsulin study, but with low background SH prevalence rates.
      CONCLUSIONS: This review provides evidence for the effectiveness of a stepped
      care approach in the management of patients with IAH, initially with structured
      diabetes education in flexible insulin therapy, which may incorporate
      psychotherapeutic and behavioral therapies, progressing to diabetes technology,
      incorporating sensors and insulin pumps, in those with persisting need.

PMID- 26207054
TI  - Glycemic Variability and Diabetes Complications: Does It Matter? Of Course It
      Does!
AB  - There is no argument that improving mean levels of glycemic control as judged by
      assays for glycated hemoglobin (HbA(1c)) reduces the risks of microvascular
      complications and cardiovascular disease events in patients with type 1 and type
      2 diabetes. However, observations in some trials have suggested that targeting
      HbA(1c) to suggested targets may not always result in improved outcomes for
      people with long-standing type 2 diabetes. The reasons why the glycemic control
      strategies that primarily use HbA(1c) in these studies did not have predicted
      outcomes are not clear. Thus, controversy remains as to whether there are
      glycemic metrics beyond HbA(1c) that can be defined as effective measures that
      can be used in addition to HbA(1c) to help in assessing the risk of an individual
      developing diabetes complications. In this regard, the concept of "glycemic
      variability" (GV) is one metric that has attracted a lot of attention. GV can be
      simply defined as the degree to which a patient's blood glucose level fluctuates
      between high (peaks) and low (nadir) levels. The best and most precise way to
      assess GV is also one that is still debated. Thus, while there is universal
      agreement that HbA(1c) is the current gold standard for the primary clinical
      target, there is no consensus as to whether other proposed glycemic metrics hold
      promise to provide additional clinical data or whether there should be additional
      targets beyond HbA(1c). Therefore, given the current controversy, we provide a
      Point-Counterpoint debate on this issue. In the point narrative below, Dr. Hirsch
      provides his argument that fluctuations in blood glucose as assessed by GV
      metrics are deleterious and control of GV should be a primary treatment target.
      In the following counterpoint narrative, Dr. Bergenstal argues that there are
      better markers to assess the risk of diabetes than GV and provides his
      consideration of other concepts.

PMID- 26207055
TI  - Glycemic Variability and Diabetes Complications: Does It Matter? Simply Put,
      There Are Better Glycemic Markers!
AB  - There is no argument that improving mean levels of glycemic control as judged by
      assays for glycated hemoglobin (HbA(1c)) reduces the risks of microvascular
      complications and cardiovascular disease events in patients with type 1 and type
      2 diabetes. However, observations in some trials have suggested that targeting
      HbA(1c) to suggested targets may not always result in improved outcomes for
      people with long-standing type 2 diabetes. The reasons why the glycemic control
      strategies that primarily use HbA(1c) in these studies did not have predicted
      outcomes are not clear. Thus, controversy remains as to whether there are
      glycemic metrics beyond HbA(1c) that can be defined as effective measures that
      can be used in addition to HbA(1c) to help in assessing the risk of an individual
      developing diabetes complications. In this regard, the concept of "glycemic
      variability" (GV) is one metric that has attracted a lot of attention. GV can be
      simply defined as the degree to which a patient's blood glucose level fluctuates
      between high (peaks) and low (nadir) levels. The best and most precise way to
      assess GV is also one that is still debated. Thus, while there is universal
      agreement that HbA(1c) is the current gold standard for the primary clinical
      target, there is no consensus as to whether other proposed glycemic metrics hold
      promise to provide additional clinical data or whether there should be additional
      targets beyond HbA(1c). Therefore, given the current controversy, we provide a
      Point-Counterpoint debate on this issue. In the preceding point narrative, Dr.
      Hirsch provides his argument that fluctuations in blood glucose as assessed by GV
      metrics are deleterious and control of GV should be a primary treatment target.
      In the counterpoint narrative below, Dr. Bergenstal argues that there are better
      markers to assess the risk of diabetes than GV and provides his consideration of
      other concepts.

PMID- 26207056
TI  - Erratum. Is There a Link Between Liraglutide and Pancreatitis? A Post Hoc Review
      of Pooled and Patient-Level Data From Completed Liraglutide Type 2 Diabetes
      Clinical Trials. Diabetes Care 2015;38:1058-1066.

PMID- 26207058
TI  - Improving Diabetes Management and Cardiovascular Risk Factors Through Peer-Led
      Self-management Support Groups in Western Kenya.

PMID- 26207059
TI  - Effects of Mobile Phone SMS to Improve Glycemic Control Among Patients With Type
      2 Diabetes in Bangladesh: A Prospective, Parallel-Group, Randomized Controlled
      Trial.

PMID- 26207061
TI  - Patient Empowerment Programme (PEP) and Risk of Microvascular Diseases Among
      Patients With Type 2 Diabetes in Primary Care: A Population-Based Propensity
      Matched Cohort Study.

PMID- 26207060
TI  - Prevalence and Regional Distribution of Autoantibodies Against GAD65Ab in a
      European Population Without Diabetes: The EPIC-InterAct Study.

PMID- 26207062
TI  - Comment on Lin et al. Risk Factors for Decline in IQ in Youth With Type 1
      Diabetes Over the 12 Years From Diagnosis/Illness Onset. Diabetes Care
      2015;38:236-242.

PMID- 26207063
TI  - Response to Comment on Lin et al. Risk Factors for Decline in IQ in Youth With
      Type 1 Diabetes Over the 12 Years From Diagnosis/Illness Onset. Diabetes Care
      2015;38:236-242.

PMID- 26207064
TI  - Comment on Nordwall et al. Impact of HbA1c, Followed From Onset of Type 1
      Diabetes, on the Development of Severe Retinopathy and Nephropathy: The VISS
      Study (Vascular Diabetic Complications in Southeast Sweden). Diabetes Care
      2015;38:308-315.

PMID- 26207065
TI  - Response to Comment on Nordwall et al. Impact of HbA1c, Followed From Onset of
      Type 1 Diabetes, on the Development of Severe Retinopathy and Nephropathy: The
      VISS Study (Vascular Diabetic Complications in Southeast Sweden). Diabetes Care
      2015;38:308-315.

PMID- 26207066
TI  - Comment on Inzucchi et al. Management of Hyperglycemia in Type 2 Diabetes, 2015:
      A Patient-Centered Approach. Update to a Position Statement of the American
      Diabetes Association and the European Association for the Study of Diabetes.
      Diabetes Care 2015;38:140-149.

PMID- 26207067
TI  - Comment on Inzucchi et al. Management of Hyperglycemia in Type 2 Diabetes, 2015:
      A Patient-Centered Approach. Update to a Position Statement of the American
      Diabetes Association and the European Association for the Study of Diabetes.
      Diabetes Care 2015;38:140-149.

PMID- 26207068
TI  - Response to Comments on Inzucchi et al. Management of Hyperglycemia in Type 2
      Diabetes, 2015: A Patient-Centered Approach. Update to a Position Statement of
      the American Diabetes Association and the European Association for the Study of
      Diabetes. Diabetes Care 2015;38:140-149.

PMID- 26207069
TI  - Bacterial community structure in freshwater springs infested with the invasive
      plant species Hydrilla verticillata.
AB  - The phylogenetic composition and physiological profiles of bacterial communities
      in freshwater springs were evaluated during the blooming and non-blooming stages
      of the invasive plant species, Hydrilla verticillata. Community-level
      physiological profiles (CLPPs) and pyrosequencing of 16S rRNA gene amplicons were
      used to study potential Hydrilla mediated shifts in the physiological potential
      and phylogenetic composition of the bacterial community in infested systems. The
      results of CLPP revealed that the microbes in the Hydrilla invaded sites utilized
      less substrates during blooming periods than during nonblooming periods of the
      plant. Spearman's rank correlation analysis showed some relationships between the
      relative abundances of bacterial taxa and the Biolog substrate utilization
      pattern. The relative abundance of the identified taxa showed some striking
      differences based on the blooming status of Hydrilla and to a lesser extent on
      site variation. The relative abundance of Actinobacteria, Bacteriodetes, and
      Verrucomicrobia was generally higher during Hydrilla blooms, while
      Deltaproteobacteria was generally higher during non-blooming stages of Hydrilla.
      The detected genera also varied based on the blooming stages of the plant. Based
      on the findings, it appears that Hydrilla alters the phylogenetic composition and
      structure of the bacterial community during the blooming stage.

PMID- 26207070
TI  - The Proto-Ribosome: an ancient nano-machine for peptide bond formation.
AB  - The ribosome is a ribozyme whose active site, the peptidyl transferase center
      (PTC) is situated within a highly conserved universal symmetrical region that
      connects all ribosomal functional centers involved in amino-acid polymerization.
      The linkage between this elaborate architecture and A-site tRNA position revealed
      that the A to P-site passage of the tRNA 3' terminus during protein synthesis is
      performed by a rotary motion, synchronized with the overall tRNA/mRNA sideways
      movement and Guided by the PTC. This rotary motion leads to suitable
      stereochemistry for peptide bond formation as well as for substrate mediated
      catalysis. Analysis of the substrate binding modes to ribosomes led to the
      hypothesis that the ancient ribosome produced single peptide bonds and non-coded
      chains, potentially in a similar manner to the modern PTC. Later in evolution, a
      mechanism, enabling some type of decoding genetic control triggered the emergence
      of the small ribosomal subunit or part of it. This seems to be the result of the
      appearance of reaction products that could have evolved after polypeptides
      capable of enzymatic function were generated sporadically, while an ancient
      stable RNA fold was converted into an old version of a tRNA molecule. As in the
      contemporary ribosome the symmetry relates only the backbone fold and nucleotides
      orientations but not nucleotide sequences, it emphasizes the superiority of
      functional requirement over sequence conservation, and indicates that the PTC may
      have evolved by gene fusion or gene duplication.

PMID- 26207071
TI  - Terpenoid-Alkaloids: Their Biosynthetic Twist of Fate and Total Synthesis.
AB  - Terpenes and alkaloids are ever-growing classes of natural products that provide
      new molecular structures which inspire chemists and possess a broad range of
      biological activity. Terpenoid-alkaloids originate from the same prenyl units
      that construct terpene skeletons. However, during biosynthesis, a nitrogen atom
      (or atoms) is introduced in the form of beta-aminoethanol, ethylamine, or
      methylamine. Nitrogen incorporation can occur either before, during, or after the
      cyclase phase. The outcome of this unique biosynthesis is the formation of
      natural products containing unprecedented structures. These complex structural
      motifs expose current limitations in organic chemistry, thus providing
      opportunities for invention. This review focuses on total syntheses of terpenoid
      alkaloids and unique issues presented by this class of natural products. More
      specifically, it examines how these syntheses relate to the way terpenoid
      alkaloids are made in Nature. Developments in chemistry that have facilitated
      these syntheses are emphasized, as well as chemical technology needed to conquer
      those that evade synthesis.

PMID- 26207072
TI  - Estrangement Between Mothers and Adult Children: The Role of Norms and Values.
AB  - Relationships between mothers and their children are expected to be lifelong and
      rewarding for both members of the dyad. Because of the salience of these ties,
      they are likely to be disrupted only under conditions of extreme relational
      tension and dissatisfaction. In this work, the authors drew on theoretical
      arguments regarding societal norm violations and value similarity to examine the
      processes that lead to estrangement between mothers and adult children. To
      address this issue, they used quantitative and qualitative data on 2,013 mother
      adult child dyads nested within 561 later life families, including 64 in which
      mothers reported being estranged from at least 1 of their children. Value
      dissimilarity was found to be a strong predictor of estrangement, whereas
      violation of serious societal norms was not. Qualitative data revealed that value
      dissimilarity created severe relational tension between mothers and adult
      children leading to estrangement.

PMID- 26207073
TI  - Structural basis for the antipolymer activity of Hb zeta2betas2 trapped in a
      tense conformation.
AB  - The phenotypical severity of sickle-cell disease (SCD) can be mitigated by
      modifying mutant hemoglobin S (Hb S, Hb alpha2betas2) to contain embryonic zeta
      globin in place of adult alpha-globin subunits (Hb zeta2betas2).
      Crystallographical analyses of liganded Hb zetazeta2betas2, though, demonstrate a
      tense (T-state) quaternary structure that paradoxically predicts its
      participation in--rather than its exclusion from--pathological deoxyHb S
      polymers. We resolved this structure-function conundrum by examining the effects
      of alpha->zeta exchange on the characteristics of specific amino acids that
      mediate sickle polymer assembly. Superposition analyses of the betas subunits of
      T-state deoxyHb alpha2betas2 and T-state CO-liganded Hb zeta2betas2 reveal
      significant displacements of both mutant betasVal6 and conserved beta-chain
      contact residues, predicting weakening of corresponding polymer-stabilizing
      interactions. Similar comparisons of the alpha- and zeta-globin subunits
      implicate four amino acids that are either repositioned or undergo non
      conservative substitution, abrogating critical polymer contacts. CO-Hb
      zeta2betas2 additionally exhibits a unique trimer-of-heterotetramers crystal
      packing that is sustained by novel intermolecular interactions involving the
      pathological betasVal6, contrasting sharply with the classical double-stranded
      packing of deoxyHb S. Finally, the unusually large buried solvent-accessible
      surface area for CO-Hb zeta2betas2 suggests that it does not co-assemble with
      deoxyHb S in vivo. In sum, the antipolymer activities of Hb zeta2betas2 appear to
      arise from both repositioning and replacement of specific alpha- and betas-chain
      residues, favoring an alternate T-state solution structure that is excluded from
      pathological deoxyHb S polymers. These data account for the antipolymer activity
      of Hb zeta2betas2, and recommend the utility of SCD therapeutics that capitalize
      on alpha-globin exchange strategies.

PMID- 26207074
TI  - The Rugheimer-Burrows reaction revisited: Facile preparation of 4
      alkylisoquinolines and 3,5-dialkylpyridines from (partially) saturated amines.
AB  - A long-known class of cyclic amine/aldehyde condensation reactions was
      reinvestigated. Benzoic acid was found to efficiently promote condensations of
      amines such as piperidine or 1,2,3,4-tetrahydroisoquinoline with aromatic
      aldehydes, resulting in amine beta-functionalization and aromatization. These
      redox-neutral transformations provide 3,5-dialkylpyridines and 4
      alkylisoquinolines in moderate to good yields, following short reaction times
      under microwave conditions.

PMID- 26207075
TI  - Judgments of self-identified gay and heterosexual male speakers: Which phonemes
      are most salient in determining sexual orientation?
AB  - While numerous studies have demonstrated that a male speaker's sexual orientation
      can be identified from relatively long passages of speech, few studies have
      evaluated whether listeners can determine sexual orientation when presented with
      word-length stimuli. If listeners are able to distinguish between self-identified
      gay and heterosexual male speakers of American English, it is unclear whether
      they form their judgments based on a phoneme, such as a vowel or consonant, or
      multiple phonemes, such as a vowel and a consonant. In this study, we first found
      that listeners can distinguish between self-identified gay and heterosexual
      speakers of American English upon hearing word-length stimuli. We extended these
      results in a separate experiment to demonstrate that listeners primarily rely on
      vowels, and to some extent consonants, when forming their judgments. Listeners
      were able to differentiate between the two groups of speakers for each of the
      vowels and three of the seven consonants presented. In a follow-up experiment we
      found evidence that listeners' judgments improved if they were presented with
      multiple phonemes, such as a vowel and /s/. These results provide important
      information about how different phonemes can provide discriminant information
      about a male speaker's sexual orientation.

PMID- 26207076
TI  - Molecular imaging of biological tissue using gas cluster ions.
AB  - An Ar n+ (n = 1-6000) gas cluster ion source has been utilized to map the
      chemical distribution of lipids in a mouse brain tissue section. We also show
      that the signal from high mass species can be further enhanced by doping a small
      amount of CH4 into the Ar cluster to enhance the ionization of several
      biologically important molecules. Coupled with secondary ion mass spectrometry
      instrumentation which utilizes a continuous Ar cluster ion projectile, maximum
      spatial resolution and maximum mass resolution can be achieved at the same time.
      With this arrangement, it is possible to achieve chemically resolved molecular
      ion images at the 4-um resolution level. The focused Ar n+/[Ar x (CH4) y ]+ beams
      (4-10 um) have been applied to the study of untreated mouse brain tissue. A high
      signal level of molecular ions and salt adducts, mainly from various
      phosphocholine lipids, has been seen and directly used to map the chemical
      distribution. The signal intensity obtained using the pure Ar cluster source, the
      CH4-doped cluster source and C60 is also presented.

PMID- 26207077
TI  - Validation of Histologic Bone Analysis Following Microfil Vessel Perfusion.
AB  - The ability to examine bone vascularity using Micro-Computed Tomography (MUCT)
      following vessel perfusion with Microfil(r) and to subsequently perform
      histologic bone analysis in the same specimen would provide an efficient method
      by which the vascular and cellular environment of bone can be examined
      simultaneously. The purpose of this report is to determine if the administration
      of Microfil(r) precludes accurate histologic assessment of bone quality via
      osteocyte count and empty lacunae count. Sprague-Dawley rats (n=6) underwent
      perfusion with Microfil(r). Left hemi-mandibles were harvested, decalcified and
      underwent vascular analysis via MUCT prior to sectioning and staining with
      Gomori's Trichrome. Quantitative Histomorphometric evaluation was performed.
      Ninety-five percent confidence intervals were used to determine statistical
      differences from an established set of controls (n=12). Histologic analyses were
      successfully performed on specimens that had undergone previous perfusion.
      Quantitative measures of bone cellularity of perfused versus control specimens
      revealed no statistical difference in osteocyte count per high-power field (95.33
      versus 94.66; 95 percent CI,-7.64 to 6.30) or empty lacunae per high-power field
      (2.73 versus 1.89, 95 percent CI, -1.81 to 0.13). Here we report a statistical
      validation allowing for histological analysis of cell counts in specimens in
      which Microfil(r) perfusion has previously been performed.

PMID- 26207078
TI  - Predicting and retrodicting intelligence between childhood and old age in the 6
      Day Sample of the Scottish Mental Survey 1947.
AB  - In studies of cognitive ageing it is useful and important to know how stable are
      the individual differences in cognitive ability from childhood to older age, and
      also to be able to estimate (retrodict) prior cognitive ability differences from
      those in older age. Here we contribute to these aims with new data from a follow
      up study of the 6-Day Sample of the Scottish Mental Survey of 1947 (original N =
      1208). The sample had cognitive, educational, social, and occupational data
      collected almost annually from age 11 to 27 years. Whereas previous long-term
      follow-up studies of the Scottish mental surveys are based upon group
      administered cognitive tests at a mean age of 11 years, the present sample each
      had an individually-administered revised Binet test. We traced them for vital
      status in older age, and some agreed to take several mental tests at age 77 years
      (N = 131). The National Adult Reading Test at age 77 correlated .72 with the
      Terman-Merrill revision of the Binet Test at age 11. Adding the Moray House Test
      No. 12 score from age 11 and educational information took the multiple R to .81
      between youth and older age. The equivalent multiple R for fluid general
      intelligence was .57. When the NART from age 77 was the independent variable
      (retrodictor) along with educational attainment, the multiple R with the Terman
      Merrill IQ at age 11 was .75. No previous studies of the stability of
      intelligence from childhood to old age, or of the power of the NART to retrodict
      prior intelligence, have had individually-administered IQ data from youth. About
      two-thirds, at least, of the variation in verbal ability in old age can be
      captured by cognitive and educational information from youth. Non-verbal ability
      is less well predicted. A short test of pronunciation-the NART-and brief
      educational information can capture well over half of the variation in IQ scores
      obtained 66 years earlier.

PMID- 26207080
TI  - The Causal Effects of Rural-to-Urban Migration on Children's Wellbeing in China.
AB  - China's rural-to-urban migration has affected 12.6 million school-age rural
      children who have migrated with their parents and another 22 million who have
      been left behind by their migrant parents. Not enough is known, either
      theoretically or empirically, about the causal impact of migration on the
      wellbeing of this large number of Chinese children affected by migration.
      Propensity score matching methods are applied to estimate the effects of
      migration in children 10-15 years old from a 2010 national survey (N = 2,417).
      Children's migration has significant positive effects on their objective
      wellbeing but no negative effects on their subjective wellbeing. There is little
      difference between the left-behind and non-migrant children across multiple life
      domains. The Rosenbaum bounds tests indicate that the causal effects of child
      migration are sensitive to hidden bias for certain outcomes, but not for others.

PMID- 26207079
TI  - Planning and Decision Making for Care Transitions.
AB  - The need to plan for future health care and residential adjustments increases
      with age, growing frailty, and restrictions in coverage of long-term care and
      will continue to grow with population aging. Older adults' lack of financial
      preparation for health care costs, insufficient knowledge about available
      options, and inadequate communication about care-related values has become an
      increasing public health challenge. This chapter describes a model of Preparation
      for Future Care (PFC), which encompasses different levels and domains of
      planning. Research about the extent to which planning is helpful in navigating
      care transitions is reviewed, and barriers and facilitators of planning including
      individual, familial, cultural, and national long-term care policy factors are
      discussed. Planning in the context of dementia and practical approaches that can
      be taken to enhance PFC is addressed, as well as recommendations for future
      research in the area of planning and decision making in the context of care
      transitions.

PMID- 26207081
TI  - Fabrication and characterization of non-linear parabolic microporous membranes.
AB  - Large scale fabrication of non-linear microporous membranes is of technological
      importance in many applications ranging from separation to microfluidics.
      However, their fabrication using traditional techniques is limited in scope. We
      report on fabrication and characterization of non-linear parabolic micropores
      (PMS) in polymer membranes by utilizing flow properties of fluids. The shape of
      the fabricated PMS corroborated well with simplified Navier-Stokes equation
      describing parabolic relationship of the form L - t1/2. Here, L is a measure of
      the diameter of the fabricated micropores during flow time (t). The surface of
      PMS is smooth due to fluid surface tension at fluid-air interface. We demonstrate
      fabrication of PMS using curable polydimethylsiloxane (PDMS). The parabolic shape
      of micropores was a result of interplay between horizontal and vertical fluid
      movements due to capillary, viscoelastic, and gravitational forces. We also
      demonstrate fabrication of asymmetric "off-centered PMS" and an array of PMS
      membranes using this simple fabrication technique. PMS containing membranes with
      nanoscale dimensions are also possible by controlling the experimental
      conditions. The present method provides a simple, easy to adopt, and energy
      efficient way for fabricating non-linear parabolic shape pores at microscale. The
      prepared parabolic membranes may find applications in many areas including
      separation, parabolic optics, micro-nozzles / -valves / -pumps, and microfluidic
      and microelectronic delivery systems.

PMID- 26207082
TI  - Addressing Key Technical Aspects of Quantum Dot Probe Preparation for Bioassays.
AB  - Fluorescent semiconductor nanoparticles, or quantum dots, have become a promising
      platform for the engineering of biofunctional probes for a variety of biomedical
      applications, ranging from multicolor imaging to single-molecule tracking to
      traceable drug delivery. Advances in organometallic synthesis have enabled
      preparation of hydrophobic quantum dots with high quantum yields and narrow size
      distribution, offering bright optical materials with narrow size-tunable emission
      profiles. At the same time, polymer encapsulation procedures provided a simple
      and versatile methodology for transferring hydrophobic nanoparticles into
      physiologically-relevant aqueous buffers. Taken together, hydrophobic
      nanoparticle platforms and polymer encapsulation should offer great flexibility
      for implementation of novel probe designs. However, the success of the
      encapsulation and purification depends on many factors often overlooked in the
      scientific literature, such as close match between nanoparticle and polymer
      physicochemical properties and dimensions, slow dynamics of polymer arrangement
      on the nanoparticle surface, and the size and charge similarity of resultant
      polymer-coated quantum dots and empty byproduct polymer micelles. To make this
      general hydrophobic nanoparticle modification strategy accessible by a broad
      range of biomedical research groups, we focus on the important technical aspects
      of nanoparticle polymer encapsulation, purification, bioconjugation, and
      characterization.

PMID- 26207083
TI  - In Vitro Reconstitution of Metabolic Pathways: Insights into Nature's Chemical
      Logic.
AB  - In vitro analysis of metabolic pathways is becoming a powerful method to gain a
      deeper understanding of Nature's core biochemical transformations. With
      astounding advancements in biotechnology, purification of a metabolic pathway's
      constitutive enzymatic components is becoming a tractable problem, and such in
      vitro studies allow scientists to capture the finer details of enzymatic reaction
      mechanisms, kinetics, and the identity of organic product molecules. In this
      review, we present eleven metabolic pathways that have been the subject of in
      vitro reconstitution studies in the literature in recent years. In addition, we
      have selected and analyzed subset of four case studies within these eleven
      examples that exemplify remarkable organic chemistry occurring within biology.
      These examples serves as tangible reminders that Nature's biochemical routes obey
      the fundamental principles of organic chemistry, and the chemical mechanisms are
      reminiscent of those featured in traditional synthetic organic routes. The
      illustrations of biosynthetic chemistry depicted in this review may inspire the
      development of biomimetic chemistries via abiotic chemical techniques.

PMID- 26207084
TI  - A Simulation Study on a Single-Unit Wireless EEG Sensor.
AB  - Traditional EEG systems are limited when utilized in point-of-care applications
      due to its immobility and tedious preparation procedures. We are designing a
      novel device named single-unit wireless EEG sensor to solve these problems. The
      sensor has a size similar to a U.S. penny. Four electrodes are installed within a
      20mm diameter cylinder. It can be applied to scalp in seconds to amplify,
      digitize and wirelessly transmit EEG. Before the design and construction of an
      actual sensor, in this paper, we perform a set of simulations to quantitatively
      study: 1) can the sensor acquire EEG reliably? 2) will the selection of sensor
      orientation be an important factor to influence signal strength? Our results
      demonstrate positive answers to these questions. Moreover, the signal sensor
      acquired appears to be comparable to the signal from the standard 10-20 system.
      These results warrant the further design and construction of a single-unit
      wireless EEG sensor.

PMID- 26207085
TI  - Heat conductivity of DNA double helix.
AB  - Thermal conductivity of isolated single molecule DNA fragments is of importance
      for nanotechnology, but has not yet been measured experimentally. Theoretical
      estimates based on simplified (1D) models predict anomalously high thermal
      conductivity. To investigate thermal properties of single molecule DNA we have
      developed a 3D coarse-grained (CG) model that retains the realism of the full all
      atom description, but is significantly more efficient. Within the proposed model
      each nucleotide is represented by 6 particles or grains; the grains interact via
      effective potentials inferred from classical molecular dynamics (MD) trajectories
      based on a well-established all-atom potential function. Comparisons of 10 ns
      long MD trajectories between the CG and the corresponding all-atom model show
      similar root-mean-square deviations from the canonical B-form DNA, and similar
      structural fluctuations. At the same time, the CG model is 10 to 100 times faster
      depending on the length of the DNA fragment in the simulation. Analysis of
      dispersion curves derived from the CG model yields longitudinal sound velocity
      and torsional stiffness in close agreement with existing experiments. The
      computational efficiency of the CG model makes it possible to calculate thermal
      conductivity of a single DNA molecule not yet available experimentally. For a
      uniform (polyG-polyC) DNA, the estimated conductivity coefficient is 0.3 W/mK
      which is half the value of thermal conductivity for water. This result is in
      stark contrast with estimates of thermal conductivity for simplified, effectively
      1D chains ("beads on a spring") that predict anomalous (infinite) thermal
      conductivity. Thus, full 3D character of DNA double-helix retained in the
      proposed model appears to be essential for describing its thermal properties at a
      single molecule level.

PMID- 26207086
TI  - Long-range modulation of a composite crystal in a five-dimensional superspace.
AB  - The intergrowth crystal of n-tetracosane/urea presents a misfit parameter,
      defined by the ratio gamma = ch /cg (chost/cguest), that is very close to a
      commensurate value (gamma ? 1/3). High-resolution diffraction studies presented
      here reveal an aperiodic misfit parameter of gamma = 0.3369, which is found to be
      constant at all temperatures studied. A complex sequence of structural phases is
      reported. The high temperature phase (phase I) exists in the four-dimensional
      superspace group P6122(00gamma). At Tc1 = 179(1) K, a ferroelastic phase
      transition increases the dimension of the crystallographic superspace. This
      orthorhombic phase (phase II) is characterized by the five-dimensional (5D)
      superspace group C2221(00gamma)(10delta) with a modulation vector ao* + cm* = ao*
      + delta . ch*, in which the supplementary misfit parameter is delta = 0.025(1) in
      host reciprocal units. This corresponds to the appearance of a modulation of very
      long period (about 440 +/- 16 A). At Tc2 = 163.0(5) K, a 5D to 5D phase
      transition leads to the crystallographic superspace group
      P212121(00gamma)(00delta) with a very similar value of delta. This phase
      transition reveals a significant hysteresis effect.

PMID- 26207087
TI  - Interprofessional analysis of esthetical deformity from long head biceps
      tenotomy.
AB  - OBJECTIVE: To evaluate the perception of an esthetical deformity resultant from
      arthroscopic long head biceps (LHB) tenotomy according to the degree of
      experience of the assisting professional. METHODS: 120 patients submitted to
      shoulder surgery were photographed and photos were mounted in a PowerPoint
      presentation. Three shoulder specialist surgeons, three generalist orthopedic
      surgeons and three graduated residents analyzed the presentation. RESULTS: On all
      patients we observed most agreement among the shoulder specialists. When just the
      patients with LHB tenotomy were analyzed, the specialists agreed moderately, the
      generalists had small agreement and the residents, a poor one. Analyzing patients
      with BMI < 30, there was major agreement between the specialists, while the
      generalists and residents had poor agreement. Analyzing patients with BMI >= 30,
      the generalists had small kappa agreement, while the specialists and residents
      had no agreement. CONCLUSIONS: The perception of an esthetical deformity
      regarding a LHB tenotomy did not have significant agreement between different
      level of professionals, even though the specialists showed similar perception on
      tenotomy patients. The evaluation of obese patients lowered the agreement on the
      three groups of professionals. Level of Evidence III. Case Control Study.

PMID- 26207088
TI  - Evaluation of isometric strength and fatty infiltration of the subscapularis in
      latarjet surgery.
AB  - OBJECTIVE: To evaluate the function of the subscapularis muscle by means of
      isometric strength, clinical examination and analysis of fatty infiltration in
      patients with recurrent anterior dislocation of the shoulder undergoing Latarjet
      Patte surgery. METHODS: 38 patients operated from March 2011 to March 2012, with
      minimum follow-up of two years were evaluated, being 26 males and 12 females,
      with a mean age of 28.7 years old. Isometric strength was measured using a
      portable dynamometer and measuring the distance from the back of the hand during
      the lift-off test. We used the Rowe and Walch-Duplay scores for clinical
      evaluation. The degree of fatty infiltration of the subscapularis belly was
      assessed by computed tomography. RESULTS: The mean scores in the Walch-Duplay and
      Rowe were 84.7 and 89.4, respectively. The mean distance to the back of the hand
      was 7.34 cm on the operated side and 8.72 cm on the opposite side (p <0.0001).
      The mean strength measured in the lift-off test was 0.38 kg lower than on the
      contralateral side (p = 0.001). There was no fatty infiltration of the
      subscapularis in 16 patients (42.1%). Sixteen patients (42.1%) were classified as
      Goutallier grade 1 and six (15.8%) as grade 2. We found that the measured
      isometric strength decreases with increasing the degree of fatty infiltration (p
      <0.0001). CONCLUSIONS: The decrease in subscapularis strength, albeit of low
      magnitude (0.38 kg), was directly related to the degree of fatty infiltration and
      worse clinical outcomes. Level of Evidence III, Therapeutic Study - Investigating
      the Results of Treatment.

PMID- 26207089
TI  - Evaluation of arthroscopic treatment of posterior shoulder instability.
AB  - OBJECTIVE: To provide data for the analysis of arthroscopy as a method of
      surgical treatment for shoulder and discuss its actual indications and
      preliminary results. METHODS: We evaluated 15 patients submitted to reverse
      Bankart arthroscopic surgery. We used the UCLA (University of California at Los
      Angeles) score to measure the results before surgery and 12 months thereafter.
      RESULTS: The average UCLA score changed from 26.67+/-0.25 (SD 0.97) before
      surgery to 34.20+/-0.53 (SD 2.04) after surgery. The effectiveness of surgery was
      93%. In five cases loose bodies were found. A patient undergoing remplissage was
      evaluated separately. The data did not change after 24 months post-surgery.
      CONCLUSION: The arthroscopic treatment of posterior shoulder instability and
      posterior dislocation of the shoulder has been proved feasible and results in our
      series followed the same trends as in the literature. Level of Evidence III,
      Transversal Retrospective Study.

PMID- 26207090
TI  - Functional evaluation of patients with surgically treated terrible triad of the
      elbow.
AB  - OBJECTIVES: To evaluate the functional outcome of patients with surgically
      treated terrible triad of the elbow. METHODS: A retrospective evaluation was
      performed using the MEPS score (Mayo Elbow Performance Score) of patients
      diagnosed with terrible triad of the elbow who underwent surgical treatment.
      RESULTS: 14 patients (nine men and five women) and 15 elbows (one bilateral case)
      were evaluated. A MEPS average score of 78 points and 86% good and excellent
      results was obtained. As complications, we had one case of infection and three of
      neuropraxia of the ulnar nerve. CONCLUSION: The patients had stable elbow with
      good function, however with reduced range of motion. Level of Evidence IV, Case
      Series.

PMID- 26207091
TI  - Evaluation of rotator cuff muscle strength in healthy individuals.
AB  - OBJECTIVE: To compare the strength generated by the rotator muscles of the
      shoulder joint between the right upper limb and left upper limb among healthy
      individuals. METHODS: To evaluate the muscle strength of upper limbs from
      isometric contractions in the horizontal direction (rotation) an isometric
      dynamometer was used, equipped with transducers, signal conditioning, a data
      acquisition board, and finally, a computer. Study participants were 22 male
      military subjects, aged between 18 and 19 years old, body mass between 57.7 and
      93.0 kg (71.8 +/- 9.45 kg) and height between 1.67 and 1.90 m (1.75 +/- 0.06 m),
      healthy and without clinical diseases or any type of orthopedic injury in the
      muscle skeletal system. RESULTS: The internal rotation in the right upper limb
      (RUL) was higher than the average strength of internal rotation in the left upper
      limb (LUL) (p = 0.723). The external rotation strength in RUL was lower than the
      average strength of external rotation in the LUL (p=0.788). No statistical
      difference was observed by comparing the strength values of all isometric
      strength tests. CONCLUSION: For the sample and methodology used to assess muscle
      strength, there was no statistical difference between the strength generated by
      the muscles of the rotator cuff of the right and left upper limbs. Experimental
      Study.

PMID- 26207092
TI  - Prognostic factors for clinical outcomes after rotator cuff repair.
AB  - OBJECTIVE: To identify prognostic factors of postoperative functional outcomes.
      METHODS: Retrospective case series evaluating patients undergoing rotator cuff
      repair, analyzed by the UCLA score (pre and 12-month postoperative) and Magnetic
      Resonance Imaging (preoperative). Patients' intrinsic variables related to the
      injury and intervention were evaluated. Multivariate linear regression analysis
      was performed to determine variables impact on postoperative functional
      assessment. RESULTS: 131 patients were included. The mean UCLA score increased
      from 13.17 +/- 3.77 to 28.73 +/- 6.09 (p<0,001). We obtained 65.7% of good and
      excellent results. Age (r= 0.232, p= 0.004) and reparability of posterosuperior
      injuries (r= 0.151, p= 0.043) correlated with the functional assessment at 12
      months. After multivariate linear regression analysis, only age was associated (p
      = 0.008). CONCLUSIONS: The surgical treatment of rotator cuff tears lead to good
      and excellent results in 65.6% of patients. Age was an independent predictor
      factor with better clinical outcomes by UCLA score in older patients. Level of
      Evidence IV, Case Series.

PMID- 26207093
TI  - Spastic wrist flexion in cerebral palsy. Pronator teres versus flexor carpi
      ulnaris transfer.
AB  - OBJECTIVE: Analize data on patients submitted to transfer of the pronator teres
      (PT) or the flexor carpi ulnaris (FCB) to the extensor carpi radialis
      longus/brevis (ECRL/B) in order to correct flexed wrist deformity in patients
      with cerebral palsy. METHOD: Patients were divided into two groups: PT group and
      FCU group to ECRL/B. The results were evaluated by goniometry and by the
      functional hand test (FHT). RESULTS: Goniometry showed a statistically
      significant difference in favor of FCU transfer. There was no statistically
      significant difference regarding FHT. CONCLUSION: Both transfers PT and FCU to
      ECRB are good options to correct wrist flexion deformity in cerebral palsy. Level
      of Evidence III, Non-randomized Controlled Cohort/Follow-Up Study.

PMID- 26207094
TI  - Biomechanical study of the sacroiliac fracture fixation with titanium rods and
      pedicle screws.
AB  - OBJECTIVES: To assess biomechanically different fixations means of the sacroiliac
      joint with pedicle screws and to compare the traditional head height with reduced
      ones. METHODS: We used a polyethylene model representing the pelvic ring and
      simulated a unilateral sacroiliac dislocation. We set up three different
      constructions: 1) two screws attached to a rod; 2) two rods connected to two
      small head screws each; and 3) two rods connected to two average headed screws
      each. We conducted tests in a biomechanical testing and a mechanized processing
      laboratory. RESULTS: Group 1 supported an average maximum load of 99.70 N. Group
      2 supported an average maximum load of 362.46 N. Group 3 endured an average
      maximum load of 404.15 N. In the assembly with one rod, the resistance decreased
      as compared with the one with two bars: 72.5 % compared to small-headed screws
      and 75.3 % to the traditional screw. CONCLUSION: The assembly with a single bar
      presented inferior results when compared to the double bar assembly. There was no
      statistical difference in the results between the screws used. Experimental
      Study.

PMID- 26207095
TI  - Prevalence of falls in elderly women.
AB  - OBJECTIVE: To verify prevalence of falls and fear of falling, and to compare
      functional fitness among elderly women fallers and non-fallers. METHODS: Seventy
      eight elderly women participated in this study. Cases of falls and the fear of
      falling were self-reported by the elderly women, while the functional fitness was
      measured by a set of functional tests. Mean and standard deviation were used to
      describe the sample. Independent t-test was used to compare functional fitness
      between groups. RESULTS: The prevalence of falls in this sample was 32.4%. Among
      women fallers, 40% self-reported a high fear of falling. CONCLUSION: It is
      recommended that functional and resistance exercises are included in the
      preventive strategies for reducing risk factors for falls and its determinants in
      elderly women. Level of Evidence II, Prognostic-Prospective Study.

PMID- 26207096
TI  - Subjective results of joint lavage and viscosupplementation in hemophilic
      arthropathy.
AB  - OBJECTIVE: To assess whether joint lavage, viscosupplementation and triamcinolone
      improve joint pain, function and quality of life in patients with severe
      hemophilic arthropathy. METHODS: Fourteen patients with knee and/or ankle
      hemophilic arthritis with and without involvement of other joints underwent joint
      lavage and subsequent injection of hylan G-F20 and triamcinolone in all affected
      joints. The patients answered algo-functional questionnaires (Lequesne and
      WOMAC), visual analog scale for pain (VAS) and SF-36 preoperatively, and at one,
      three, six and twelve months postoperatively. RESULTS: Sixteen knees, 15 ankles,
      8 elbows and one shoulder were treated in 14 patients. Six patients had
      musculoskeletal bleeding [ankle (1), leg muscle (2) and knees (4)] at 3 months
      affecting the results. Pain did not improve significantly. Function improved
      (WOMAC p=0.02 and Lequesne p=0.01). The physical component of SF-36 improved at
      all time points except at 3 months, with best results at one-year follow-up
      (baseline = 33.4; 1 month = 39.6; 3 months= 37.6; 6 months 39.6 and 1 year =
      44.6; p < 0.001). CONCLUSION: Joint lavage followed by injection of triamcinolone
      and hylan G-F20 improves function and quality of life progressively up to a year,
      even in severe hemophilic arthropathy. Level of Evidence IV, Case Series.

PMID- 26207099
TI  - Imaging biophysics of axonal transport with MEMRI: Optic tract transport is
      altered in mouse model of Alzheimer's disease.

PMID- 26207097
TI  - Stent thrombosis caused by metal allergy complicated by protein S deficiency and
      heparin-induced thrombocytopenia: a case report and review of the literature.
AB  - A 43-year-old woman recipient of a bare metal coronary stent during an acute
      anterior myocardial infarction was repeatedly hospitalized with recurrent stent
      thrombosis (ST) over the following 3 years. Emergent coronary angiography showed
      a thrombus in the in-stent segment of the proximal left anterior descending
      artery. We repeatedly aspirated the thrombus, which immediately reformed multiple
      times. The discontinuation of heparin and administration of thrombolytics and
      argatroban, followed by repeated balloon dilatations, ended the formation of new
      thrombi. The patient was found to be allergic to nickel, protein S deficient and
      carrier of heparin-induced thrombocytopenia antibody. We discuss this case in the
      context of a) literature pertaining to acute coronary syndromes in the young, and
      b) the detailed investigations needed to identify thrombotic risk factors.
      Steroids may be effective to prevent recurrent ST caused by stent allergy. 

PMID- 26207098
TI  - Primary Structure of a Trypsin Inhibitor (Copaifera langsdorffii Trypsin
      Inhibitor-1) Obtained from C. langsdorffii Seeds.
AB  - In this study, the aim was to determine the complete sequence of the Copaifera
      langsdorffii trypsin inhibitor (CTI)-1 using 2-dimensional (2D)-PAGE, matrix
      assisted laser desorption ionization-time-of-flight (MALDI-TOF), and quadrupole
      time-of-flight (QTOF) spectrometry. Spots A (CTI-1) and F (CTI-2) were submitted
      to enzymatic digestions with trypsin, SV8, and clostripain. The accurate mass of
      the peptide obtained from each digest was determined by mass spectrometry (MS)
      using MALDI-TOF. The most abundant peptides were purified and sequenced in a
      liquid chromatograph connected to an electrospray ionization-QTOF MS. When the
      purified trypsin inhibitor was submitted to 2D electrophoresis, different spots
      were observed, suggesting that the protein is composed of 2 subunits with
      microheterogeneity. Isoelectric points of 8.0, 8.5, and 9.0 were determined for
      the 11 kDa subunit and of 4.7, 4.6, and 4.3 for the 9 kDa subunit. The primary
      structure of CTI-1, determined from the mass of the peptide of the enzymatic
      digestions and the sequence obtained by MS, indicated 180 shared amino acid
      residues and a high degree of similarity with other Kunitz (KTI)-type inhibitors.
      The peptide also contained an Arg residue at the reactive site position. Its 3
      dimensional structure revealed that this is because the structural discrepancies
      do not affect the canonical conformation of the reactive loop of the peptide.
      Results demonstrate that a detailed investigation of the structural
      particularities of CTI-1 could provide a better understanding of the mechanism of
      action of these proteins, as well as clarify its biologic function in the seeds.
      CTI-1 belongs to the KTI family and is composed of 2 polypeptide chains and only
      1 disulfide bridge. 

PMID- 26207100
TI  - Equal Learning Does Not Result in Equal Remembering: The Importance of Post
      Encoding Processes.
AB  - Explanations of variability in long-term recall typically appeal to encoding
      and/or retrieval processes. However, for well over a century, it has been
      apparent that for memory traces to be stored successfully, they must undergo a
      post-encoding process of stabilization and integration. Variability in post
      encoding processes is thus a potential source of age-related and individual
      variance in long-term recall. We examined post-encoding variability in each of
      two experiments. In each experiment, 20-month-old infants were exposed to novel
      three-step sequences in each of three encoding conditions: watch only, imitate,
      and learn to criterion. They were tested for recall after 15 min (as a measure of
      the success of encoding) and either weeks (1, 2, or 3: Experiment 1) or days (1,
      2, or 4: Experiment 2) later. In each experiment, differential relative levels of
      performance among the conditions were observed at the two tests. The results
      implicate post-encoding processes are a source of variance in long-term recall.

PMID- 26207101
TI  - Intrasensory Redundancy Facilitates Infant Detection of Tempo: Extending
      Predictions of the Intersensory Redundancy Hypothesis.
AB  - Research has demonstrated that intersensory redundancy (stimulation synchronized
      across multiple senses) is highly salient and facilitates processing of amodal
      properties in multimodal events, bootstrapping early perceptual development. The
      present study is the first to extend this central principle of the intersensory
      redundancy hypothesis (IRH) to certain types of intrasensory redundancy
      (stimulation synchronized within a single sense). Infants were habituated to
      videos of a toy hammer tapping silently (unimodal control), depicting
      intersensory redundancy (synchronized with a soundtrack) or intrasensory
      redundancy (synchronized with another visual event; light flashing or bat
      tapping). In Experiment 1, 2-month-olds showed both intersensory and intrasensory
      facilitation (with respect to the unimodal control) for detecting a change in
      tempo. However, intrasensory facilitation was found when the hammer was
      synchronized with the light flashing (different motion) but not with the bat
      tapping (same motion). Experiment 2 tested 3-month-olds using a somewhat easier
      tempo contrast. Results supported a similarity hypothesis: intrasensory
      redundancy between two dissimilar events was more effective than that between two
      similar events for promoting processing of amodal properties. These findings
      extend the IRH and indicate that in addition to intersensory redundancy,
      intrasensory redundancy between two synchronized dissimilar visual events is also
      effective in promoting perceptual processing of amodal event properties.

PMID- 26207102
TI  - Measurement Invariance of the Short Inventory of Problems-Revised Across African
      American and Non-Latino White Substance Users.
AB  - This study investigated measurement invariance properties of the Short Inventory
      of Problems - Revised (SIP-R) across racial groups. The sample included 195
      African American and 194 non-Latino White adult participants in a clinical trial
      investigating the effectiveness of motivational enhancement therapy in the
      National Institute on Drug Abuse Clinical Trials Network. The SIP-R demonstrated
      configural invariance and weak metric invariance, suggesting conceptualizations
      of adverse consequences of substance use are equivalent across racial groups. The
      SIP-R also indicated partial strong/scalar and strict metric invariance,
      suggesting a need for continued research of SIP-R items to ensure valid
      measurement and outcomes across racial groups.

PMID- 26207103
TI  - Evaluation of a Training to Reduce Provider Bias Toward Pregnant Patients With
      Substance Abuse.
AB  - The objective of this article is not to present a scientific or systematic study,
      but to provide an initial framework for designing a training workshop to enhance
      health practitioners' (nurses, social workers, physicians, etc.) knowledge
      regarding substance abuse treatment and to decrease their bias toward substance
      abusing women, particularly pregnant women in rural communities. We incorporated
      the 4 Transdisciplinary Foundations from the Substance Abuse and Mental Health
      Services Administration Competencies Model, with specific competencies targeted
      that related to provider bias. After the conference, 52 of the 70 participants
      completed a questionnaire to self-assess knowledge level and confidence in skill
      related to substance abuse management. Participant mean scores were statistically
      significantly higher following the conference than 1 week prior ( p < .001) in
      the area of "gender difference with substance abuse," moving from an average of
      2.6 to 4.5 on a 5-point Likert scale. Our conference was successful in increasing
      attendees' knowledge about gender difference and substance abuse among pregnant
      patients.

PMID- 26207104
TI  - Benchmarking the Bethe-Salpeter Formalism on a Standard Organic Molecular Set.
AB  - We perform benchmark calculations of the Bethe-Salpeter vertical excitation
      energies for the set of 28 molecules constituting the well-known Thiel's set,
      complemented by a series of small molecules representative of the dye chemistry
      field. We show that Bethe-Salpeter calculations based on a molecular orbital
      energy spectrum obtained with non-self-consistent G0W0 calculations starting from
      semilocal DFT functionals dramatically underestimate the transition energies.
      Starting from the popular PBE0 hybrid functional significantly improves the
      results even though this leads to an average -0.59 eV redshift compared to
      reference calculations for Thiel's set. It is shown, however, that a simple self
      consistent scheme at the GW level, with an update of the quasiparticle energies,
      not only leads to a much better agreement with reference values, but also
      significantly reduces the impact of the starting DFT functional. On average, the
      Bethe-Salpeter scheme based on self-consistent GW calculations comes close to the
      best time-dependent DFT calculations with the PBE0 functional with a 0.98
      correlation coefficient and a 0.18 (0.25) eV mean absolute deviation compared to
      TD-PBE0 (theoretical best estimates) with a tendency to be red-shifted. We also
      observe that TD-DFT and the standard adiabatic Bethe-Salpeter implementation may
      differ significantly for states implying a large multiple excitation character.

PMID- 26207105
TI  - Actively Decoupled Transmit-Receive Coil-Pair for Mouse Brain MRI.
AB  - A low-cost, high performance RF coil-pair for MR imaging of mouse brain is
      described. A surface receiving coil is used for high spin-sensitivity, while a
      larger transmit coil, located outside the mouse holder, delivers good B1
      uniformity across the brain with reasonable efficiency. The volume coil is
      constructed with an open architecture, making experimental setup easy and
      providing clear access to the head of the mouse. Each coil is switched between
      active and inactive modes using PIN diodes driven by a small amplifier external
      to the spectrometer. Because of this active decoupling, there is no requirement
      for orthogonal orientation of the coils. The coil pair is platform independent,
      requiring only a transmit/receive (T/R) signal to switch the amplifier that
      drives the PIN diodes, and can therefore be used with virtually any commercial or
      home-built MR scanner.

PMID- 26207106
TI  - The Warburg effect: a balance of flux analysis.
AB  - Cancer metabolism is characterized by increased macromolecular syntheses through
      coordinated increases in energy and substrate metabolism. The observation that
      cancer cells produce lactate in an environment of oxygen sufficiency (aerobic
      glycolysis) is a central theme of cancer metabolism known as the Warburg effect.
      Aerobic glycolysis in cancer metabolism is accompanied by increased pentose cycle
      and anaplerotic activities producing energy and substrates for macromolecular
      synthesis. How these processes are coordinated is poorly understood. Recent
      advances have focused on molecular regulation of cancer metabolism by oncogenes
      and tumor suppressor genes which regulate numerous enzymatic steps of central
      glucose metabolism. In the past decade, new insights in cancer metabolism have
      emerged through the application of stable isotopes particularly from 13C carbon
      tracing. Such studies have provided new evidence for system-wide changes in
      cancer metabolism in response to chemotherapy. Interestingly, experiments using
      metabolic inhibitors on individual biochemical pathways all demonstrate similar
      system-wide effects on cancer metabolism as in targeted therapies. Since
      biochemical reactions in the Warburg effect place competing demands on available
      precursors, high energy phosphates and reducing equivalents, the cancer metabolic
      system must fulfill the condition of balance of flux (homeostasis). In this
      review, the functions of the pentose cycle and of the tricarboxylic acid (TCA)
      cycle in cancer metabolism are analyzed from the balance of flux point of view.
      Anticancer treatments that target molecular signaling pathways or inhibit
      metabolism alter the invasive or proliferative behavior of the cancer cells by
      their effects on the balance of flux (homeostasis) of the cancer metabolic
      phenotype.

PMID- 26207107
TI  - A novel perineal shield for low-dose-rate prostate brachytherapy.
AB  - PURPOSE: To study the impact on radiation exposure to staff through the use of an
      original perineal shield during low-dose-rate prostate brachytherapy. MATERIAL
      AND METHODS: We designed a 1 mm thick stainless steel shield that duplicates and
      is able to slide directly over a standard commercialized prostate brachytherapy
      grid. We then analyzed the post-procedure exposure in 15 consecutive patients who
      underwent Iodine-125 seed placement. Measurements were performed with and without
      the shield in place at fixed locations relative to the grid template. Endpoints
      were analyzed using the paired two-sample t-test, with statistical significance
      defined as a p-value < 0.05. RESULTS: The exposure at the midline grid template
      ranged from 0.144-0.768 mSv/hr without the shield, and 0.038-0.144 mSv/hr with
      the shield (p < 0.0001). The exposure 10 cm left of the grid template was 0.134
      0.576 mSv/hr without the shield, and 0.001-0.012 mSv/hr with the shield (p <
      0.0001). The exposure 10 cm right of the grid template was 0.125-0.576 mSv/hr
      without the shield, and 0.001-0.012 mSv/hr with the shield (p < 0.0001). The
      median reduction of exposure at the grid was 76% midline, 98.5% left, and 99%
      right. Similarly, each individual dose rate was recorded at 25 cm from the
      perineum, both with and without shield. The median reduction of exposure 25 cm
      from the perineum was 73.7% midline, 77.7% left and 81.6% right (p < 0.0001).
      CONCLUSIONS: Our novel shield took seconds to install and was non-restrictive
      during the procedure, and provided at least a four-fold reduction in radiation
      exposure to the brachytherapist.

PMID- 26207108
TI  - Evaluation of the dosimetric impact of loss and displacement of seeds in prostate
      low-dose-rate brachytherapy.
AB  - PURPOSE: To analyze the seed loss and displacement and their dosimetric impact in
      prostate low-dose-rate (LDR) brachytherapy while utilizing the combination of
      loose and stranded seeds. MATERIAL AND METHODS: Two hundred and seventeen
      prostate cancer patients have been treated with LDR brachytherapy. Loose seeds
      were implanted in the prostate center and stranded seeds in the periphery of the
      gland. Patients were imaged with transrectal ultrasound before implant and with
      computerized tomography/magnetic resonance imaging (CT/MR) one month after
      implant. The seed loss and displacement had been analyzed. Their impact on
      prostate dosimetry had been examined. The seed distribution beyond the prostate
      inferior boundary had been studied. RESULTS: The mean number of seeds per patient
      that were lost to lung, pelvis/abdomen, urine, or unknown destinations was 0.21,
      0.13, 0.03, and 0.29, respectively. Overall, 40.1% of patients had seed loss.
      Seed migration to lung and pelvis/abdomen occurred in 15.5% and 10.5% of the
      patients, respectively. Documented seed loss to urine was found in 3% of the
      patients while 20% of patients had seed loss to unknown destinations. Prostate
      length difference between pre-plan and post-implant images was within 6 mm in
      more than 98% of cases. The difference in number of seeds inferior to prostate
      between pre-plan and post-implant dosimetry was within 7 seeds for 93% of
      patients. At time of implant, 98% of seeds, inferior to prostate, were within 5
      mm and 100% within 15 mm, and in one month post-implant 83% within 9 mm and 96.3%
      within 15 mm. Prostate post-implant V100, D90, and rectal wall RV100 for patients
      without seed loss were 94.6%, 113.9%, and 0.98 cm(3), respectively, as compared
      to 95.0%, 114.8%, and 0.95 cm(3) for the group with seed loss. CONCLUSIONS: Seed
      loss and displacement have been observed to be frequent. No correlation between
      seed loss and displacement and post-plan dosimetry has been reported.

PMID- 26207109
TI  - Effect of a urinary catheter on seed position and rectal and bladder doses in CT
      based post-implant dosimetry for prostate cancer brachytherapy.
AB  - PURPOSE: To assess the variability in rectal and bladder dosimetric parameters
      determined according to post-implant computed tomography (CT) images in patients
      with or without a urethral catheter. MATERIAL AND METHODS: Patients with prostate
      cancer who were scheduled to undergo CT after brachytherapy between October 2012
      and January 2014 were included. We obtained CT series with and without a urinary
      catheter in each patient. We compared the rectal and bladder doses in 18 patients
      on each CT series. RESULTS: The shifts in the seed positions between with and
      without a catheter in place were 1.3 +/- 0.3 mm (mean +/- standard deviation).
      The radiation doses to the rectum, as determined on the CT series, with a
      urethral catheter were higher than those on CT without a catheter (p < 0.001).
      Radiation doses to the bladder with a catheter were significantly lower than
      those without a catheter (p = 0.027). CONCLUSIONS: Post-implant dosimetry (PID)
      with no catheter showed significantly lower rectal doses and higher bladder doses
      than those of PID with a catheter. We recommend the PID procedure for CT images
      in patients without a catheter. Use of CT with a catheter is limited to
      identifying urethral position.

PMID- 26207110
TI  - Short-term clinical outcome and dosimetric comparison of tandem and ring versus
      tandem and ovoids intracavitary applicators.
AB  - PURPOSE: To compare the short-term toxicity and dosimetry of tandem and ring
      (TR), and tandem and ovoid (TO) applicators in treatment of gynecologic
      malignancy. MATERIAL AND METHODS: Following pelvic external beam radiation
      therapy (EBRT), a total of 52 computed tomography-based plans from 13 patients
      with cervical cancer (FIGO IB2-IIIB) were evaluated for HDR brachytherapy.
      Prescription was 7 Gy to the ICRU point A for four weekly fractions.
      Gastrointestinal and genitourinary toxicities were evaluated. Clinical target
      volume (CTV) and organs at risk were delineated on CT scans. Bladder, rectum, and
      sigmoid mean doses and D2cc were calculated. Treatment time and irradiated tissue
      volume were compared. Percent of CTV receiving 100% (CTV100%) of the prescribed
      dose as well as the percent of the prescription dose covering 90% of the CTV
      (D90) were evaluated. RESULTS: Gastrointestinal and genitourinary toxicities were
      not different between TO and TR applicators. No significant differences in the
      dose to the right and left point A, or the left point B were observed. TO
      delivered a higher dose to right point B. Organs at risk doses were similar
      between the two applicators, except mean rectal dose was lower for TO applicator.
      Overall, TO treats a larger tissue volume than TR. Mean treatment time was
      shorter for TR. Tumor coverage (D90 and CTV100%) was equivalent between TO and TR
      applicators. CONCLUSION: Although TO treats a larger tissue volume than TR, short
      term toxicities and tumor coverage are similar. Long-term clinical outcomes will
      be elucidated with longer follow up period.

PMID- 26207111
TI  - Patterns of care study of brachytherapy in New South Wales: malignancies of the
      uterine corpus.
AB  - PURPOSE: There are limited data at a population level on adjuvant brachytherapy
      (BT) practice for uterine corpus malignancies. The aims of the current study were
      to describe BT practice for this disease in New South Wales (NSW), to assess
      quality of BT, and to determine if a caseload effect on quality exists. MATERIAL
      AND METHODS: Patient, tumour, and treatment related data were collected from all
      nine NSW radiation oncology departments that treated patients with BT. Included
      patients had malignancy of the uterine corpus with treatment including BT.
      Brachytherapy quality was assessed using published quality benchmarks. Higher
      gynaecological BT caseload departments were compared with lower caseload
      departments. RESULTS: One hundred sixty-three NSW residents with gynaecological
      cancer were treated with BT. The four higher gynaecological BT caseload
      departments treated a median of 25.5 NSW residents (range 22-38), compared to
      median 10 (range 3-18) in the five lower caseload departments. Seventy-five
      patients underwent BT for uterine malignancies. Most patients had early stage
      endometrioid disease and were treated adjuvantly with intravaginal cylinders
      using high-dose-rate BT. Doses were in accordance with guideline recommendations
      in 83% of cases, and BT was appropriately indicated in 76% of cases. Higher
      caseload departments were more likely to treat with guideline doses (96% vs. 53%,
      p < 0.001) but there was no difference in compliance rate with treatment
      indications (p = 0.75). CONCLUSIONS: Brachytherapy patients, techniques, and
      numbers/unit for uterine corpus malignancies were similar in NSW compared to the
      USA but more dispersed than in Western Europe. Doses prescribed may not be
      optimal in lower gynaecological BT caseload departments - the significance of
      this represents an area in which more research is needed.

PMID- 26207112
TI  - Efficacy and safety of electronic brachytherapy for superficial and nodular basal
      cell carcinoma.
AB  - PURPOSE: Surface electronic brachytherapy (EBT) is an alternative radiotherapy
      solution to external beam electron radiotherapy and high-dose-rate radionuclide
      based brachytherapy. In fact, it is also an alternative solution to surgery for a
      subgroup of patients. The objective of this work is to confirm the clinical
      efficacy, toxicity and cosmesis of a new EBT system, namely Esteya((r)) in the
      treatment of nodular and superficial basal cell carcinoma (BCC). MATERIAL AND
      METHODS: This is a prospective single-center, non-randomized pilot study to
      assess the efficacy and safety of EBT in nodular and superficial BCC using the
      Esteya((r)) system. The study was conducted from June 2014 to February 2015. The
      follow up time was 6 months for all cases. RESULTS: Twenty patients with 23
      lesions were included. A complete response was documented in all lesions (100%).
      A low level of toxicity was observed after the 4(th) fraction in all cases.
      Erythema was the most frequent adverse event. Cosmesis was excellent, with more
      than 60% of cases without skin alteration and with subtle changes in the rest.
      CONCLUSIONS: Electronic brachytherapy with Esteya((r)) appears to be an
      effective, simple, safe, and comfortable treatment for nodular and superficial
      BCC associated with excellent cosmesis. It could be a good choice for elderly
      patients, patients with contraindications for surgery (due to comorbidities or
      anticoagulant drugs) or patients where surgery would result in a more disfiguring
      outcome. A longer follow-up and more studies are needed to confirm these
      preliminary results.

PMID- 26207113
TI  - Improved source path localisation in ring applicators and the clinical impact for
      gynecological brachytherapy.
AB  - PURPOSE: The path of subsequent dwell positions of an afterloader source being
      moved through a ring applicator for cervix cancer brachytherapy deviates from an
      ideal circle and the position of marker wires. This can lead to deviations of
      several millimetres between real and assumed dwell positions for treatment
      planning with simplified source path models. The aim of this study was to test
      video- and autoradiography-based methods for source path determination, and to
      study the influence of dwell position accuracy on dose-volume histogram (DVH)
      parameters. MATERIAL AND METHODS: Videos of the exact motion of the source wire
      through three different (r = 26, 30, 34 mm) computed tomography/magnetic
      resonance (CT/MR) compatible plastic ring applicators were recorded. Observed
      dwell positions covering the whole length of each applicators channel were used
      to adjust the circular source path model. The agreement of the true source
      positions derived from video analysis with those of the corrected circular source
      path was verified using autoradiography. The impact of an accurate source path
      definition on dose planning was analysed by simulating clinically relevant
      uncertainties in 10 clinical treatment plans. RESULTS: Depending on the ring
      size, source path diameters had to be increased by 0.5-1.0 mm in order to achieve
      acceptable maximum differences between observed and corrected dwell positions
      (1.3-2.0 mm). Autoradiography analysis showed a positional accuracy within +/- 3
      mm (extended standard deviation k = 2). For shifts of +/- 2.5 mm for even all
      dwell positions, the systematic and random variation of the D2cm(3) for bladder,
      rectum, and sigmoid was within 3%, while the impact on DVH uncertainties was much
      smaller for clinical target volume (CTV)HR and gross tumour volume (GTV).
      CONCLUSIONS: It is strongly advised to verify the real source path for ring
      applicators during acceptance testing in order to assure accurate source path
      definition and dose planning. Autoradiography can be used for source path
      verification with acceptable accuracy for treatment planning and dose reporting.

PMID- 26207114
TI  - Second salvage treatment for local recurrence of prostate cancer using high-dose
      rate brachytherapy: a case report.
AB  - PURPOSE: Currently, there are no recommendations for the management of a second
      local recurrence of prostate adenocarcinoma except for the introduction of
      androgen deprivation therapy (ADT). CASE REPORT: A 69-year-old man underwent a
      third salvage local treatment with high-dose-rate brachytherapy (HDRB), for a
      second biochemical relapse for local recurrence. Thirty-five Grays in 5 fractions
      were delivered on the whole prostate extended to the proximal part of left
      seminal vesicle. Given the availability of new treatment techniques in our
      radiation therapy department, a dosimetric comparison between HDRB and
      stereoatactic radiosurgery (SRS) was performed. RESULTS: Immediate tolerance of
      HDRB was acceptable with achievement of prostate specific antigen (PSA) nadir in
      24 months (0.03 ng/ml). Observed late toxicities were only grade 2 urinary
      incontinence. Dosimetric comparison showed a slight advantage on clinical target
      volume coverage and rectum protection for the SRS. The HDRB showed an advantage
      on bone irradiation including femoral heads and the volume receiving 0.5 Gy (EQD2
      = 1 Gy with alpha/beta = 3). CONCLUSIONS: A third local treatment with good
      tolerance could be a therapeutic option in case of a second local prostate cancer
      recurrence in order to delay, as long as possible, the chemical castration. Both
      techniques (HDRB and SRS) seem valid and should be chosen based on the
      availability and experience in a treatment center.

PMID- 26207115
TI  - High-dose-rate brachytherapy - a novel treatment approach for primary clear cell
      adenocarcinoma of male urethra.
AB  - The incidence of male urethral cancer is rare with age preponderance of 50 to 60
      years. The standard management approach is surgery. Here, we present a novel
      treatment approach for male urethral cancer. Thirty-six year old male, case of
      primary clear cell adenocarcinoma of urethra who refused surgery, underwent
      cystoscopic assisted intraluminal HDR brachytherapy. Patient received a dose of
      36 Gy in 9 fractions (4 Gy per fraction) followed by a boost of 24 Gy in 6
      fractions. At 11 months post treatment, disease is well controlled with no post
      treatment toxicity so far. Intraluminal brachytherapy seems to be an effective
      novel treatment for male urethral cancer. 

PMID- 26207116
TI  - Salvage brachytherapy in combination with interstitial hyperthermia for locally
      recurrent prostate carcinoma following external beam radiation therapy: a
      prospective phase II study.
AB  - Optimal treatment for patients with only local prostate cancer recurrence after
      external beam radiation therapy (EBRT) failure remains unclear. Possible curative
      treatments are radical prostatectomy, cryosurgery, and brachytherapy. Several
      single institution series proved that high-dose-rate brachytherapy (HDRBT) and
      pulsed-dose-rate brachytherapy (PDRBT) are reasonable options for this group of
      patients with acceptable levels of genitourinary and gastrointestinal toxicity. A
      standard dose prescription and scheme have not been established yet, and the
      literature presents a wide range of fractionation protocols. Furthermore,
      hyperthermia has shown the potential to enhance the efficacy of re-irradiation.
      Consequently, a prospective trial is urgently needed to attain clear structured
      prospective data regarding the efficacy of salvage brachytherapy with adjuvant
      hyperthermia for locally recurrent prostate cancer. The purpose of this report is
      to introduce a new prospective phase II trial that would meet this need. The
      primary aim of this prospective phase II study combining Iridium-192
      brachytherapy with interstitial hyperthermia (IHT) is to analyze toxicity of the
      combined treatment; a secondary aim is to define the efficacy (bNED, DFS, OS) of
      salvage brachytherapy. The dose prescribed to PTV will be 30 Gy in 3 fractions
      for HDRBT, and 60 Gy in 2 fractions for PDRBT. During IHT, the prostate will be
      heated to the range of 40-47 degrees C for 60 minutes prior to brachytherapy dose
      delivery. The protocol plans for treatment of 77 patients. 

PMID- 26207117
TI  - Outpatient combined intracavitary and interstitial cervical brachytherapy:
      barriers and solutions to implementation of a successful programme - a single
      institutional experience.
AB  - Involvement of parametrial disease in locally advanced cervical patients poses a
      challenge for women undergoing brachytherapy. Current use of the Fletcher suit
      applicator may not adequately cover the high risk clinical target volume (HR
      CTV), especially in the parametrial region due to the physical qualities of
      brachytherapy from the inverse square law and the need to respect organs at risk
      (OAR) constraints, and leads to lower local control rates. Combined intracavitary
      and interstitial brachytherapy with the use of 1 or 2 interstitial needles allows
      adequate coverage of the HR CTV and the clinical evidence have demonstrated a
      correlation with better clinical results. This procedure is often resource
      intensive, requiring inpatient stay and magnetic resonance imaging (MRI)
      planning. In departments where such resources are limited, there is a poor uptake
      of interstitial brachytherapy. This article discusses the technique of combined
      intracavitary and interstitial brachytherapy in an outpatient setting, and
      explores the issues and barriers for implementation and suggestions to overcome
      such barriers. 

PMID- 26207118
TI  - Ethnicity, Russification, and Excess Mortality in Kazakhstan.
AB  - Russians experience higher adult mortality than Central Asians despite higher
      socioeconomic status. This study exploits Kazakhstan's relatively heterogeneous
      population and geographic diversity to study ethnic differences in cause-specific
      mortality. In multivariate regression, all-cause mortality rates for Russian men
      is 27% higher than for Kazakh men, and alcohol-related death rates among Russian
      men are 2.5 times higher (15% and 4.1 times higher for females, respectively).
      Significant mortality differentials exist by ethnicity for external causes and
      alcohol-related causes of death. Adult mortality among Kazakhs is higher than
      previously found among Kyrgyz and lower than among Russians. The results suggest
      that ethnic mortality differentials in Central Asia may be related to the degree
      of russification, which could be replicating documented patterns of alcohol
      consumption in non-Russian populations.

PMID- 26207119
TI  - Review of Suicide Prevention Programs: Massachusetts, United States, in
      Comparison with Seoul.
AB  - Suicide is a tragedy that has massive impact on society. In order to prevent
      suicide, active government intervention is necessary. The suicide rate in Seoul
      is rapidly increasing and is more than five times higher than that in the state
      of Massachusetts (MA) during the last decade, especially in the elderly. The
      suicide prevention program of MA is one of the most effective suicide prevention
      programs in the United States. The program views suicide as a preventable public
      health problem, and emphasizes treatment of depression and de-stigmatization of
      mental health illnesses to prevent suicide. Also, through active collaboration
      with mental health professionals, they try to identify at-risk populations and
      help them to get medical interventions. The program also actively collaborates
      with the regional coalition program and the Samaritans in taking care of the
      elderly, and supports the elderly in feeling worthwhile after retirement by
      helping them to work for communities as volunteers. For its part, the Seoul
      suicide prevention program puts more emphasis on "life respect culture" and
      "emotional support to high risk individuals by regular visiting". The annual
      budget of the Seoul suicide prevention program is one-quarter and that for mental
      health is about one-twentieth that of MA. Considering the high suicide rate and
      lower mental health service usage in Seoul, it is crucial to raise awareness of
      depression and decrease the stigma on mental illnesses. Furthermore, educational
      efforts with long-term investment in research on suicide are necessary. 

PMID- 26207120
TI  - Psychometric Properties of a Short Korean Version of the Revised Obsessive
      Intrusion Inventory.
AB  - OBJECTIVE: The Revised Obsessive Intrusion Inventory (ROII) is a 52-item scale
      that evaluates obsessional intrusive thoughts. The aim of the present study was
      to validate a short, 20-item Korean version of the ROII (ROII-20). METHODS: Of
      the 1125 participants who completed the ROII-20, 895 participants completed the
      scale to examine the factor structure of the scale. A subgroup of these
      participants (n=53) completed the scale twice to determine test-retest
      reliability. To establish external validity, 230 participants completed the scale
      and other questionnaires. RESULTS: Exploratory factor analyses suggested a
      hierarchical model comprising two higher order factors of autogenous obsessions
      (resulting from aggressive thoughts and sexual thoughts) and reactive obsessions
      (resulting from thoughts about contamination, thoughts about accidents, and
      thoughts about dirt). Confirmatory factor analyses supported this model. The
      results indicated good internal consistency and test-retest reliability. External
      validity was supported by relationships with obsessive-compulsive symptoms and
      general distress. CONCLUSION: The ROII-20 presents good psychometric properties
      and may be considered as a promising instrument for measuring obsessional
      intrusions.

PMID- 26207121
TI  - Reliability and Validity of the Korean Young Schema Questionnaire-Short Form-3 in
      Medical Students.
AB  - OBJECTIVE: The Young Schema Questionnaire (YSQ) is a self-report measure of early
      maladaptive schemas and is currently in its third revision; it is available in
      both long (YSQ-L3) and short (YSQ-S3) forms. The goal of this study was to
      develop a Korean version of the YSQ-S3 and establish its psychometric properties
      in a Korean sample. METHODS: A total of 542 graduate medical students completed
      the Korean version of the YSQ-S3 and several other psychological scales. A
      subsample of 308 subjects completed the Korean YSQ-S3 both before and after a 2
      year test-retest interval. Correlation, regression, and confirmatory factor
      analyses were performed on the data. RESULTS: The internal consistency of the 90
      item Korean YSQ-S3 was 0.97 and that of each schema was acceptable, with
      Cronbach's alphas ranging from 0.59 to 0.90. The test-retest reliability ranged
      from 0.46 to 0.65. Every schema showed robust positive correlations with most
      psychological measures. The confirmatory factor analysis for the 18-factor
      structure originally proposed by Young, Klosko, and Weishaar (2003) showed that
      most goodness-of-fit statistics were indicative of a satisfactory fit.
      CONCLUSION: These findings support the reliability and validity of the Korean
      version of the YSQ-S3.

PMID- 26207122
TI  - Normative Study of the Literacy Independent Cognitive Assessment in Illiterate
      and Literate Elderly Koreans.
AB  - OBJECTIVE: The aim of this study was to provide normative data on the Literacy
      Independent Cognitive Assessment (LICA) and to explore the effects of age,
      education/literacy, and gender on the performance of this test. METHODS: Eight
      hundred and eighty-eight healthy elderly subjects, including 164 healthy
      illiterate subjects, participated in this study. None of the participants had
      serious medical, psychiatric, or neurological disorders including dementia.
      Bivariate linear regression analyses were performed to examine the effects of
      age, education/literacy, and sex on the score in each of the LICA cognitive
      tests. The normative scores for each age and education/literacy groups are
      presented. RESULTS: Bivariate linear regression analyses revealed that total
      score and all cognitive tests of the LICA were significantly influenced by both
      age and education/literacy. Younger and more-educated subjects outperformed older
      and illiterate or less-educated subjects, respectively, in all of the tests. The
      normative scores of LICA total score and subset score were presented according to
      age (60-64, 65-69, 70-74, 75-80, and >=80 years) and educational levels
      (illiterate, and 0-3, 4-6, and >=7 years of education). CONCLUSION: These results
      on demographic variables suggest that age and education should be taken into
      account when attempting to accurately interpret the results of the LICA cognitive
      subtests. These normative data will be useful for clinical interpretations of the
      LICA neuropsychological battery in illiterate and literate elderly Koreans.
      Similar normative studies and validations of the LICA involving different ethnic
      groups will help to enhance the dementia diagnosis of illiterate people of
      different ethnicities.

PMID- 26207123
TI  - Sociodemographic Factors and Comorbidities Associated with Remission from Alcohol
      Dependence: Results from a Nationwide General Population Survey in Korea.
AB  - OBJECTIVE: The lifetime prevalence of alcohol dependence in South Korea remains
      higher than other countries. The aim of our study is to identify factors
      associated with remission from alcohol dependence. METHODS: Data from the Korean
      Epidemiological Catchment Area-Replication (KECA-R) study were used in our study.
      The Korean version of the Composite International Diagnostic Interview 2.1 (K
      CIDI 2.1) was administered. Remission was defined as having no symptom of alcohol
      dependence for 12 months or longer at the time of the interview. Demographic and
      clinical variables putatively associated with remission from alcohol dependence
      were examined by t-test, chi-square-test and logistic regression analysis.
      RESULTS: The lifetime prevalence rate of alcohol dependence was 7.0%. Among them,
      3.2% of the subjects were diagnosed with active alcohol dependence in the
      previous 12 months, and 3.8% were found to be in remission. Subjects in 35- to 44
      year-old group, not living with partner group, and lower level of educational
      attainment group were more likely to be in the active alcohol dependence state.
      Of the comorbid mental disorders, dysthymia, anxiety disorder, nicotine use, and
      nicotine dependence were more common among the actively alcohol-dependent
      subjects. CONCLUSION: There is considerable level of recovery from alcohol
      dependence. Attention to factors associated with remission from alcohol
      dependence may be important in designing more effective treatment and prevention
      programs in this high-risk population.

PMID- 26207124
TI  - Suicide Risk Assessments: Which Suicide Risk Factors Psychiatric Residents
      Consider Significant?
AB  - OBJECTIVE: Patients visiting the emergency department (ED) after a suicide
      attempt are generally assessed for suicide risk by psychiatric residents.
      Psychiatric residents' competence in evaluating the risk posed by the patients
      who attempted suicide is critical to preventing suicide. METHODS: We investigated
      factors considered important by psychiatric residents when evaluating suicide
      risk. This study included 140 patients admitted to the ED after attempting
      suicide. Psychiatric residents rated patients' severity of current and future
      suicide risk as low/moderate/high using the Brief Emergency Room Suicide Risk
      Assessment (BESRA). The association between each BESRA variable and level of
      suicide risk was analyzed. RESULTS: Many factors were commonly considered
      important in evaluating the severity of current and future suicide risk. However,
      the following factors were only associated with future suicide risk: female
      gender, having no religion, family psychiatric history, history of axis I
      disorders, having a will, harboring no regrets, and social isolation. CONCLUSION:
      Psychiatric residents use diverse factors when assessing suicide risk.
      Psychiatric residents might put more emphasis on non-modifiable demographic and
      clinical factors, concrete evidence showing suicide determination, and social
      isolation to assess the risk of future suicide.

PMID- 26207125
TI  - There Is No Difference in IQ between Suicide and Non-Suicide Psychiatric
      Patients: A Retrospective Case-Control Study.
AB  - OBJECTIVE: The goal of this study was to examine the association between IQ and
      suicide in psychiatric patients. METHODS: We conducted a nested case-control
      study using data obtained from psychiatric patients affiliated with a general
      hospital in Seoul, Korea. In a one-to-two ratio the psychiatric patients who died
      of suicide (Suicide Group; n=35) were matched to those who didn't (Non-suicide
      Group; n=70) by age, gender, psychiatric diagnosis and approximate time of first
      treatment. IQ was measured using the Korean version of the Wechsler Adult
      Intelligence Scale-Revised. RESULTS: There were no significant differences in any
      type of IQ between suicide patients and non-suicide patients. Logistic regression
      showed no evidence of an association between IQ and suicide. CONCLUSION: These
      results do not support the existence of an association between IQ and suicide.

PMID- 26207126
TI  - The Effects of Taekwondo Training on Brain Connectivity and Body Intelligence.
AB  - OBJECTIVE: Many studies have reported that Taekwondo training could improve body
      perception, control and brain activity, as assessed with an electroencephalogram.
      This study aimed to assess body intelligence and brain connectivity in children
      with Taekwondo training as compared to children without Taekwondo training.
      METHODS: Fifteen children with Taekwondo training (TKD) and 13 age- and sex
      matched children who had no previous experience of Taekwondo training (controls)
      were recruited. Body intelligence, clinical characteristics and brain
      connectivity in all children were assessed with the Body Intelligence Scale
      (BIS), self-report, and resting state functional magnetic resonance imaging.
      RESULTS: The mean BIS score in the TKD group was higher than that in the control
      group. The TKD group showed increased low-frequency fluctuations in the right
      frontal precentral gyrus and the right parietal precuneus, compared to the
      control group. The TKD group showed positive cerebellum vermis (lobe VII) seed to
      the right frontal, left frontal, and left parietal lobe. The control group showed
      positive cerebellum seed to the left frontal, parietal, and occipital cortex.
      Relative to the control group, the TKD group showed increased functional
      connectivity from cerebellum seed to the right inferior frontal gyrus.
      CONCLUSION: To the best of our knowledge, this is the first study to assess the
      effect of Taekwondo training on brain connectivity in children. Taekwondo
      training improved body intelligence and brain connectivity from the cerebellum to
      the parietal and frontal cortex.

PMID- 26207127
TI  - Literacy Independent Cognitive Assessment: Assessing Mild Cognitive Impairment in
      Older Adults with Low Literacy Skills.
AB  - OBJECTIVE: Comprehensive neuropsychological tests are important in the diagnosis
      and follow-up of patients with MCI; however, most were developed without
      consideration of illiteracy. We developed the Literacy Independent Cognitive
      Assessment (LICA) as a comprehensive neuropsychological assessment battery
      applicable to older adults who are either literate or illiterate. This study
      aimed to assess the reliability and validity of the LICA for diagnosis of MCI.
      METHODS: Normal controls (n=634) and patients with MCI (n=128) were recruited
      from 13 centers were included in this study. Participants were divided into
      illiterate or literate groups, based on their performance on a brief reading and
      writing test. The LICA, Korean Mini-Mental State Examination (K-MMSE), and Seoul
      Neuropsychological Screening Battery (SNSB) were administered. RESULTS: Total
      LICA scores distinguished MCI patients from controls (p<0.001). They were closely
      and positively correlated to the K-MMSE scores (r=0.632, p<0.001) but negatively
      correlated to clinical dementia rating (CDR) (r=-0.358, p<0.001) and CDR sum of
      boxes (r=-0.339, p<0.001). Area under the receiver operating characteristic curve
      for patients with MCI by total LICA score was 0.827 (0.783-0.870), superior to
      that presented by the K-MMSE. For the classification of MCI subtypes, inter
      method reliability of LICA with the SNSB was good (kappa 0.773; 0.679-0.867,
      p<0.001). CONCLUSION: The results of this study show that the LICA may be
      reliably used to distinguish MCI patients from cognitively intact adults, to
      identify MCI subtypes and monitor progression toward dementia, regardless of
      illiteracy.

PMID- 26207128
TI  - Impact of Cannabis Use on Long-Term Remission in Bipolar I and Schizoaffective
      Disorder.
AB  - OBJECTIVE: To investigate the impact of regular cannabis use on long-term
      remission of mood symptoms in bipolar spectrum disorders. METHODS: The 24-month
      prospective observational study included patients (n=239) with bipolar I disorder
      and schizoaffective disorder, bipolar type. Participants were classified as
      regular cannabis users (three times or more per week) or non-users. The primary
      outcome measure was the achievement of remission on the evaluations during the 24
      months. RESULTS: Of the 234 participants for whom data was available, 25 (10.7%)
      were regular cannabis users, and the group comprised significantly more males
      than females. In the total population, cannabis use was significantly associated
      with decreased likelihood of remission during the 24-month follow-up period.
      Subgroup analyses showed that cannabis use was significantly associated with
      lower remission rates on the Hamilton Depression Rating Scale in females (n=139)
      and patients prescribed mood stabilizers alone (n=151), whereas in males (n=95)
      and patients prescribed olanzapine and/or a mood stabilizer (n=83), cannabis use
      was significantly associated with lower remission rates on the Young Mania Rating
      Scale. Remission rates were lowest in the concurrent cannabis and tobacco smoking
      group (n=22) followed by the tobacco smoking only group (n=97), and the non
      smoker group (n=116). The post-hoc analysis revealed that all remission rates
      were significantly lower in the concurrent cannabis and the tobacco smoking group
      compared to the non-smoker group. CONCLUSION: Cannabis use negatively affects the
      long-term clinical outcome in patients with bipolar spectrum disorders. A
      comprehensive assessment and integrated management of cannabis use are required
      to achieve better treatment outcomes for bipolar spectrum disorders.

PMID- 26207129
TI  - Bioequivalence of Generic and Brand Name Clozapine in Korean Schizophrenic
      Patients: A Randomized, Two-Period, Crossover Study.
AB  - OBJECTIVE: Clozapine is the treatment of choice for refractory schizophrenia. The
      aim of this study was to compare the pharmacokinetics of the brand name
      (Clozaril) formulation and a generic formulation (Clzapine) of clozapine in
      Korean schizophrenic patients. METHODS: A prospective, randomized, crossover
      study was conducted to evaluate the steady-state pharmacokinetic profiles of
      Clozaril and Clzapine. Schizophrenic patients were randomized to receive either
      the brand name or generic formulation (100 mg twice daily) for 10 days, followed
      by the other formulation for 10 days. Plasma samples were collected on the last
      day of each treatment period. RESULTS: Twenty-two of 28 patients (78.6%)
      completed the study. The mean Cmax,ss values for Clzapine and Clozaril were
      524.62 and 551.18 ng/mL, and the mean AUC0-12 values were 4479.90 hr.ng/mL and
      4724.56 hr.ng/mL, respectively. The 90% CI values for the natural logarithmically
      transformed Cmax,ss and AUC0-12 ratios (Clzapine to Clozaril) after a single oral
      dose (100 mg) were 0.934 (0.849-1.028) and 0.936 (0.869-1.008), respectively.
      Five patients (20.8%) among 24 patients who took Clzapine reported 11 adverse
      events and six adverse events were reported by four patients (15.4%) among 26 who
      took Clozaril; there were no significant differences on physical examination or
      in vital signs, ECG, and laboratory tests between groups. CONCLUSION: Generic
      clozapine (Clzapine) appears to be bioequivalent to brand name clozapine
      (Clozaril).

PMID- 26207130
TI  - Evaluation of Oxidative Metabolism in Child and Adolescent Patients with
      Attention Deficit Hyperactivity Disorder.
AB  - OBJECTIVE: Oxidative metabolism is impaired in several medical conditions
      including psychiatric disorders, and this imbalance may be involved in the
      etiology of these diseases. The present study evaluated oxidative balance in
      pediatric and adolescent patients with attention deficit hyperactivity disorder
      (ADHD). METHODS: The study included 48 children and adolescents (34 male, 14
      female) with ADHD who had no neurological, systemic, or comorbid psychiatric
      disorders, with the exception of oppositional defiant disorder (ODD), and 24 sex-
      and age-matched healthy controls (17 male and seven female). RESULTS: TAS was
      significantly lower, and TOS and OSI were significantly higher in patients with
      ADHD than in healthy controls. Total antioxidant levels were lower in patients
      with comorbid ODD than in those with no comorbidity. No difference was found in
      TOS or OSI among the ADHD subtypes; however, TAS was higher in the attention
      deficient subtype. CONCLUSION: Our findings demonstrated that oxidative balance
      is impaired and oxidative stress is increased in children and adolescents with
      ADHD. This results are consistent with those of previous studies.

PMID- 26207131
TI  - Microstructural Changes of Anterior Corona Radiata in Bipolar Depression.
AB  - OBJECTIVE: In bipolar disorder, dysregulation of mood may result from white
      matter abnormalities that change fiber tract length and fiber density. There are
      few studies evaluating the white matter microstructural changes in bipolar I
      patients (BD) with depressive episodes. The present study aimed to evaluate
      anterior corona radiata in BD patients with depressive episode using Diffusion
      Tensor Imaging (DTI). METHODS: Twenty-one patients with bipolar depression and 19
      healthy controls were investigated and groups were matched for age and gender.
      Diffusion-weighted echoplanar brain images (DW-EPI) were obtained using a 1.5 T
      MRI scanner. Regions of interest (ROIs) were manually placed on directional maps
      based on principal anisotropy. Apparent diffusion coefficient (ADC) and
      fractional anisotropy (FA) values of white matter were measured in the anterior
      corona radiata (ACR) bilaterally by diffusion tensor imaging. RESULTS: There was
      not a significant difference between groups of age and gender (p>0.05).
      Significantly lower FA was observed in bilateral ACR in bipolar patients with
      depression compared with healthy individuals. And there is significantly higher
      ADC values in the left frontal corona radiate in bipolar patients. CONCLUSION:
      White matter abnormalities can be detected in patients with BD using DTI. The
      neuropathology of these abnormalities is unclear, but neuronal and axonal loss,
      myelin abnormalities and reduced white matter fiber density are likely to be
      relevant.

PMID- 26207132
TI  - Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with
      Social Anxiety Disorder Using Resting-State Functional MRI.
AB  - OBJECTIVE: We hypothesize that the amplitude of low-frequency fluctuations (ALFF)
      is involved in the altered regional baseline brain function in social anxiety
      disorder (SAD). The aim of the study was to analyze the altered baseline brain
      activity in drug-naive adult patients with SAD. METHODS: We investigated
      spontaneous and baseline brain activities by obtaining the resting-state
      functional magnetic resonance imaging data of 20 drug-naive adult SAD patients
      and 19 healthy controls. Voxels were used to analyze the ALFF values using one-
      and two-sample t-tests. A post-hoc correlation of clinical symptoms was also
      performed. RESULTS: Our findings show decreased ALFF in the bilateral insula,
      left medial superior frontal gyrus, left precuneus, left middle temporal gyrus,
      right middle temporal pole, and left fusiform gyrus of the SAD group. The SAD
      patients exhibited significantly increased ALFF in the right inferior temporal
      gyrus, right middle temporal gyrus, bilateral middle occipital gyrus, orbital
      superior frontal gyrus, right fusiform gyrus, right medial superior frontal
      gyrus, and left parahippocampal gyrus. Moreover, the Liebowitz Social Anxiety
      Scale results for the SAD patients were positively correlated with the mean Z
      values of the right middle occipital and right inferior occipital but showed a
      negative correlation with the mean Z values of the right superior temporal gyrus
      and right medial superior frontal gyrus. CONCLUSION: These results of the altered
      regional baseline brain function in SAD suggest that the regions with abnormal
      spontaneous activities are involved in the underlying pathophysiology of SAD
      patients.

PMID- 26207133
TI  - Analysis of Association between Norepinephrine Transporter Gene Polymorphisms and
      Personality Traits of NEO-FFI in a Japanese Population.
AB  - OBJECTIVE: Norepinephrine is an important chemical messenger that is involved in
      mood and stress in humans, and is reabsorbed by the norepinephrine transporter
      (NET). According to Cloninger's theory, the noradrenergic system mediates the
      personality trait of reward dependence. Thus far, although association studies on
      NET gene polymorphisms and Cloninger's personality traits have been reported,
      they yielded inconsistent results. Therefore, in the present study we
      investigated whether or not the 1287G/A, -182T/C and -3081A/T polymorphisms of
      the NET gene (SLC6A2) are associated with reward dependence-related traits, as
      assessed by the five-factor model. METHODS: After written informed consent was
      obtained from participants, the three NET gene polymorphisms were analyzed by
      polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP),
      and personality was assessed by the Neuroticism Extraversion Openness-Five Factor
      Inventory (NEO-FFI) in 270 Japanese university students. RESULTS: A significant
      relation was found between the -3081A/T functional promoter polymorphism and NEO
      FFI scores: those with the T allele exhibited a lower extraversion (E) score than
      those without the T allele (Mann-Whitney U-test: z=-3.861, p<0.001). However,
      there was no correlation between the other NET gene polymorphisms and E score,
      and no association with other dimensions and these three polymorphisms.
      CONCLUSION: We conclude that the -3081A/T functional polymorphism in the NET gene
      may affect the extraversion of reward dependence-related traits, as measured by
      NEO-FFI. However, we used only the shortened version of NEO-PI-R in this study.
      Further investigations are necessary using the full version of self-rating
      personality questionnaires.

PMID- 26207134
TI  - Microarray Analysis of the Major Depressive Disorder mRNA Profile Data.
AB  - OBJECTIVE: Major depressive disorder (MDD) is a common mood disorder associated
      with several psychophysiological changes like disturbances of sleep, appetite, or
      sexual desire, and it affects the patients' life seriously. We aimed to explore a
      genetic method to investigate the mechanism of MDD. METHODS: The mRNA expression
      profile (GSE53987) of MDD was downloaded from Gene Expression Omnibus database,
      including 105 samples of three brain regions in post-mortem tissue suffered from
      MDD and unaffected controls. Differentially expressed genes (DEGs) in MDD were
      identified using the Limma package in R. Gene Ontology functions and Kyoto
      Enrichment of Genes and Genomes pathways of the selected DEGs were enriched using
      Database for Annotation, Visualization and Integrated Discovery. Protein-protein
      interactive network of DEGs was constructed using the Cytoscape software.
      RESULTS: Totally, 241 DEGs in MDD-hip group, 218 DEGs in MDD-pfc group, and 327
      DEGs in MDD-str group were identified. Also, different kinds of biological
      processes of DEGs in each group were enriched. Besides, glycan biosynthesis of
      DEGs in MDD-str group, RIG-I-like receptor signaling and pyrimidine metabolism of
      DEGs in the MDD-hip group were enriched, respectively. Moreover, several DEGs
      like PTK2, TDG and CETN2 in MDD-str group, DCT, AR and GNRHR in MDD-pfc group,
      and AKT1 and IRAK1 in MDD-hip group were selected from PPI network. CONCLUSION:
      Our data suggests that the brain striatum tissue may be greatly affected by MDD,
      and DEGs like PTK2, GALNT2 and GALNT2 in striatum, AR in prefrontal cortex and
      IRAK1 and IL12A in hippocampus may provide novel therapeutic basis for MDD
      treatment.

PMID- 26207135
TI  - Multivariate Analysis of Relationship between Childhood Trauma and Psychotic
      Symptoms in Patients with Schizophrenia.
AB  - The aim of this study was to examine the relationship between childhood trauma
      and psychotic symptoms in schizophrenic patients after controlling for the
      possible confounding factors, such as depression and dissociative symptoms.
      Ninety-eight schizophrenic inpatients participated. Childhood trauma was examined
      using the Childhood Trauma Questionnaires (CTQ), which consists of physical abuse
      (PA), sexual abuse (SA), emotional abuse (EA), physical neglect (PN), and
      emotional neglect (EN). Positive and Negative Syndrome Scale (PANSS),
      Dissociative Experience Scale (DES), and Beck's Depression Inventory (BDI) were
      also administered. Data were analyzed by partial correlation and general linear
      model. The total score of CTQ was positively correlated with positive, general,
      and total scores of PANSS. All five types of childhood trauma were associated
      with dissociative symptoms. EA and EN were positively correlated with depressive
      symptoms. Only SA significantly predicted positive symptoms of schizophrenia
      after controlling for age, sex, BDI, and DES scores, with a dose-response
      relationship between SA and positive symptoms. 

PMID- 26207137
TI  - The Joint Effects of Body Mass Index and MAOA Gene Polymorphism on Depressive
      Symptoms.
AB  - The objective of the present study was to examine the joint effects of the body
      mass index and the MAOA gene polymorphism on depressive symptoms. In two
      independent Chinese samples, we measured adolescents' depressive symptoms and
      body mass index and collected their DNA. The results indicated that the main
      effects of the MAOA gene polymorphism on depressive symptoms were significant.
      However, the main effects of body mass index and the interaction of the MAOA gene
      polymorphism and body mass index on depressive symptoms were not significant. By
      using Chinese adolescents, this study confirmed that the MAOA gene polymorphism
      directly influenced adolescents' depressive symptoms. 

PMID- 26207136
TI  - CDH13 and HCRTR2 May Be Associated with Hypersomnia Symptom of Bipolar
      Depression: A Genome-Wide Functional Enrichment Pathway Analysis.
AB  - Although bipolar disorder is highly heritable, the identification of specific
      genetic variations is limited because of the complex traits underlying the
      disorder. We performed a genome-wide association study of bipolar disorder using
      a subphenotype that shows hypersomnia symptom during a major depressive episode.
      We investigated a total of 2,191 cases, 1,434 controls, and 703,012 single
      nucleotide polymorphisms (SNPs) in the merged samples obtained from the
      Translational Genomics Institute and the Genetic Association Information Network.
      The gene emerging as the most significant by statistical analysis was rs1553441
      (odds ratio=0.4093; p=1.20*10(-5); Permuted p=6.0*10(-6)). However, the 5*0(-8)
      threshold for statistical significance required in a genome-wide association
      study was not achieved. The functional enrichment pathway analysis showed
      significant enrichments in the adhesion, development-related, synaptic
      transmission-related, and cell recognition-related pathways. For further
      evaluation, each gene of the enriched pathways was reviewed and matched with
      genes that were suggested to be associated with psychiatric disorders by previous
      genetic studies. We found that the cadherin 13 and hypocretin (orexin) receptor 2
      genes may be involved in the hypersomnia symptom during a major depressive
      episode of bipolar disorder. 

PMID- 26207138
TI  - Two Cases of Eating Disorders in Adolescents with Dental Braces Fitted Prior to
      the Onset of Anorexia Nervosa.
AB  - Orthodontic treatment typically occurs during early childhood and adolescence but
      the wearing of dental braces is often associated with sudden changes in eating
      patterns that prolong treatment into the teenage years. Despite these changes,
      psychological assessments related to eating disorders during the course of
      orthodontic treatment are often ignored. Based on the findings of the present
      case report, it is suggested that adolescent patients who wear braces and exhibit
      severe weight loss should be carefully monitored for psychiatric problems,
      including eating disorders. 

PMID- 26207139
TI  - Toward a Better Understanding of the Relationship between Childhood Trauma and
      Psychiatric Disorders: Measurement and Impact on Addictive Behaviors.

PMID- 26207140
TI  - Why Systematic Review rather than Narrative Review?

PMID- 26207141
TI  - Transferring genomics to the clinic: distinguishing Burkitt and diffuse large B
      cell lymphomas.
AB  - BACKGROUND: Classifiers based on molecular criteria such as gene expression
      signatures have been developed to distinguish Burkitt lymphoma and diffuse large
      B cell lymphoma, which help to explore the intermediate cases where traditional
      diagnosis is difficult. Transfer of these research classifiers into a clinical
      setting is challenging because there are competing classifiers in the literature
      based on different methodology and gene sets with no clear best choice;
      classifiers based on one expression measurement platform may not transfer
      effectively to another; and, classifiers developed using fresh frozen samples may
      not work effectively with the commonly used and more convenient formalin fixed
      paraffin-embedded samples used in routine diagnosis. METHODS: Here we thoroughly
      compared two published high profile classifiers developed on data from different
      Affymetrix array platforms and fresh-frozen tissue, examining their
      transferability and concordance. Based on this analysis, a new Burkitt and
      diffuse large B cell lymphoma classifier (BDC) was developed and employed on
      Illumina DASL data from our own paraffin-embedded samples, allowing comparison
      with the diagnosis made in a central haematopathology laboratory and evaluation
      of clinical relevance. RESULTS: We show that both previous classifiers can be
      recapitulated using very much smaller gene sets than originally employed, and
      that the classification result is closely dependent on the Burkitt lymphoma
      criteria applied in the training set. The BDC classification on our data exhibits
      high agreement (~95 %) with the original diagnosis. A simple outcome comparison
      in the patients presenting intermediate features on conventional criteria
      suggests that the cases classified as Burkitt lymphoma by BDC have worse response
      to standard diffuse large B cell lymphoma treatment than those classified as
      diffuse large B cell lymphoma. CONCLUSIONS: In this study, we comprehensively
      investigate two previous Burkitt lymphoma molecular classifiers, and implement a
      new gene expression classifier, BDC, that works effectively on paraffin-embedded
      samples and provides useful information for treatment decisions. The classifier
      is available as a free software package under the GNU public licence within the R
      statistical software environment through the link
      http://www.bioinformatics.leeds.ac.uk/labpages/softwares/ or on github
      https://github.com/Sharlene/BDC.

PMID- 26207142
TI  - The reliability of a smartphone goniometer application compared with a
      traditional goniometer for measuring first metatarsophalangeal joint
      dorsiflexion.
AB  - BACKGROUND: Adequate sagittal plane motion of the first metatarsalphalangeal
      joint (1st MTPJ) is important during normal gait and goniometric measurement is
      commonly used as a diagnostic and outcome assessment tool. We aimed to determine
      the intra and inter-rater reliability together with the concurrent validity of a
      universal plastic goniometer (UG) and a smartphone applicationlication (Dr G) for
      the measurement of dorsiflexion at the 1st MTPJ. METHODS: Measurement of joint
      position and passive range of motion of the 1st MTPJ dorsiflexion was compared
      using a UG and DrG goniometer. A double-blind repeated measures design was
      utilized, with intraclass correlation coefficient (ICC) used to determine levels
      of reliability. RESULTS: For joint position good intra-rater reliability (ICC
      >0.861) and good inter-rater reliability (ICC >0.823) was noted. However, the Dr
      G application consistently measured lower angles (mean 27.8 degrees  (SD 8.37))
      than the UG (mean 32 degrees  (SD 11.7)) and these associations were significant
      (r = 0.399, p < 0.001). For passive range of motion, the mean total range of
      dorsiflexion motion (from maximum plantarflexed position to maximum dorsiflexed
      position) was 82.8 degrees  (SD 12.2) for the UG and 82.9 degrees  (SD 11.3) for
      the Dr G application. Both instruments demonstrated high levels of intra-rater
      reliability (ICC >0.809). Inter-rater reliability was moderate to good for the UG
      (ICC 0.693 (95 % CI 0.580 to 0.788)) and good for the Dr G application (ICC 0.708
      (95 % CI 0.597 to 0.799)). CONCLUSIONS: Moderate to high intra and inter-rater
      reliability of joint position and passive 1st MTPJ motion can be achieved with
      traditional and smartphone-based goniometric measurement. The Dr G application
      may provide a slightly higher reliability, but devices should not be used inter
      changeably as significant variation in measurement between devices may occur.

PMID- 26207143
TI  - Foot problems in people with gout in primary care: baseline findings from a
      prospective cohort study.
AB  - BACKGROUND: Foot problems are common in people with gout yet the prevalence of
      current foot problems in people with gout and the burden they present to
      healthcare systems is not known. This cross-sectional study aimed to determine
      the prevalence and associations of hallux valgus, foot pain and disability in
      people with gout, and to assess the frequency with which foot problems lead to
      consultation with healthcare professionals. METHODS: Adults registered with 20
      general practices who had consulted their GP about gout or been prescribed
      allopurinol or colchicine in the preceding two years were mailed a questionnaire.
      Prevalence of hallux valgus, foot pain in the last month, and disabling foot pain
      in the mailed population were ascertained using validated instruments and
      estimated by inverse-weighted logistic regression. Associations with socio
      demographic, comorbid and gout-specific factors were examined using logistic
      regression. Participants were asked if they had seen health care professionals
      for foot problems within the preceding 12 months. RESULTS: One thousand one
      hundred eighty-four questionnaires were received (response 66 %). Prevalence of
      hallux valgus was 36.3 %, foot pain in the last month 22.3 % and disabling foot
      pain 14.5 %. Hallux valgus associated with age (adjusted OR 1.47 per 10-year
      increase, 95 % CI 1.26, 1.72) and female gender (2.03; 1.31, 3.15). Foot pain in
      the last month associated with age (1.24; 1.00, 1.55), obesity (BMI 30.0-34.9
      2.67; 1.32, 5.38; BMI >= 35.0 3.16; 1.44, 6.93), mild depression (2.04; 1.09,
      3.81) and polyarticular gout attacks (1.86; 1.18, 2.95). Disabling foot pain
      associated with age (1.42; 1.08, 1.87), obesity (BMI 30.0-34.9 3.73; 1.54, 9.09;
      BMI >= 35.0 4.36; 1.64, 11.64), depression (mild 2.63; 1.25, 5.53; moderate 3.53;
      1.11, 11.26) and ischaemic heart disease (2.45; 1.32, 4.53). In the previous 12
      months, 495 (42.8 %) reported consulting their GP about their feet and 281 (23.7
      %) a podiatrist/chiropodist. CONCLUSIONS: Foot problems are common in people with
      gout and frequently lead to healthcare consultation. Hallux valgus has similar
      associations to those seen in the general population, whereas foot pain
      associates with obesity and gout characteristics, and disabling foot pain with
      obesity and comorbidity. Patient assessment should consider foot problems and
      offer specific treatment where relevant.

PMID- 26207144
TI  - Characterization of the cytolethal distending toxin (typhoid toxin) in non
      typhoidal Salmonella serovars.
AB  - BACKGROUND: For many putative Salmonella enterica subsp. enterica virulence
      genes, functional characterization across serovars has been limited. Cytolethal
      distending toxin B (CdtB) is an incompletely characterized virulence factor that
      is found not only in Salmonella enterica subsp. enterica serovar Typhi
      (Salmonella Typhi) and dozens of Gram negative bacterial pathogens, but also in
      non-typhoidal Salmonella (NTS) serovars. METHODS: A comparative genomics approach
      was performed to characterize sequence conservation of the typhoid toxin (TT),
      encoded in the CdtB-islet, between Salmonella Typhi and NTS serovars. The
      cytotoxic activity of representative Salmonella enterica subsp. enterica serovars
      Javiana, Montevideo and Schwarzengrund strains and their respective isogenic cdtB
      mutants was determined in human intestinal epithelial Henle-407 cells by
      assessment of cell cycle progression of infected cells using fluorescence
      activated cell sorting (FACS). Two-way analysis of variance (ANOVA) was used to
      determine whether cdtB deletion had a significant (p < 0.05) effect on the
      percentage of Henle-407 cells at each stage of the cell cycle. RESULTS: Here we
      show that a CdtB-islet encoding the cytolethal distending toxin B (CdtB),
      pertussis-like toxin A (PltA), and pertussis-like toxin B (PltB) is present in a
      dozen NTS serovars and that these proteins have a high level of sequence
      conservation and each form monophyletic clades with corresponding Salmonella
      Typhi genes. Human epithelial Henle-407 cells infected with three representative
      CdtB-encoding NTS serovars displayed G2/M phase cell cycle arrest that was absent
      in cells infected with corresponding isogenic cdtB null mutants (p < 0.0001 for
      the factor ?cdtB deletion). CONCLUSION: Our results show that CdtB encoded by NTS
      serovars has a genomic organization, amino acid sequence conservation and
      biological activity similar to the TT, and thus, may contribute to disease
      pathogenesis.

PMID- 26207145
TI  - Virulence characteristics of hcp (+) Campylobacter jejuni and Campylobacter coli
      isolates from retail chicken.
AB  - BACKGROUND: Recently the Type VI secretion system (T6SS), which can play a
      significant role in bacterial survival and pathogenesis, was reported in
      Campylobacter spp., having the hcp gene as a key component. METHODS:
      Campylobacteriosis is associated with the consumption of infected chicken meat.
      Our study aimed to explore the presence of T6SS in C. jejuni (n = 59) and C. coli
      (n = 57) isolates, from retail raw chicken and to investigate their pathogenic
      potential. The hcp gene was used as an indicator for the T6SS presence. RESULTS:
      Using multiplex PCR we have identified a significantly higher prevalence of hcp
      in C. coli isolates (56.1%) than in C. jejuni (28.8%) and AFLP analysis of the
      isolates showed a high degree of genetic similarity between the isolates carrying
      the hcp gene. Genome sequencing data showed that 84.3% of the C. coli and 93.7%
      of the C. jejuni isolates had all 13 T6SS open reading frames. Moreover, the
      virulence characteristics of hcp + isolates, including motility and the ability
      to invade human intestinal epithelial cells in vitro, were significantly greater
      than in the control strain C. jejuni 12502; a human isolate which is hcp
      positive. CONCLUSION: Overall, it was discovered that hcp (+) C. coli and C.
      jejuni isolated from retail chicken isolates posses genetic and phenotypic
      properties associated with enhanced virulence. However, since human infections
      with C. coli are significantly less frequent than those of C. jejuni, the
      relationship between virulence factors and pathogenesis requires further study.

PMID- 26207147
TI  - REDOX IMAGING OF THE p53-DEPENDENT MITOCHONDRIAL REDOX STATE IN COLON CANCER EX
      VIVO.
AB  - The mitochondrial redox state and its heterogeneity of colon cancer at tissue
      level have not been previously reported. Nor has how p53 regulates mitochondrial
      respiration been measured at (deep) tissue level, presumably due to the
      unavailability of the technology that has sufficient spatial resolution and
      tissue penetration depth. Our prior work demonstrated that the mitochondrial
      redox state and its intratumor heterogeneity is associated with cancer
      aggressiveness in human melanoma and breast cancer in mouse models, with the more
      metastatic tumors exhibiting localized regions of more oxidized redox state.
      Using the Chance redox scanner with an in-plane spatial resolution of 200 MUm, we
      imaged the mitochondrial redox state of the wild-type p53 colon tumors (HCT116
      p53 wt) and the p53-deleted colon tumors (HCT116 p53-/-) by collecting the
      fluorescence signals of nicotinamide adenine dinucleotide (NADH) and oxidized
      flavoproteins [Fp, including flavin adenine dinucleotide (FAD)] from the mouse
      xenografts snap-frozen at low temperature. Our results show that: (1) both tumor
      lines have significant degree of intratumor heterogeneity of the redox state,
      typically exhibiting a distinct bi-modal distribution that either correlates with
      the spatial core-rim pattern or the "hot/cold" oxidation-reduction patches; (2)
      the p53-/- group is significantly more heterogeneous in the mitochondrial redox
      state and has a more oxidized tumor core compared to the p53 wt group when the
      tumor sizes of the two groups are matched; (3) the tumor size dependence of the
      redox indices (such as Fp and Fp redox ratio) is significant in the p53-/- group
      with the larger ones being more oxidized and more heterogeneous in their redox
      state, particularly more oxidized in the tumor central regions; (4) the H&E
      staining images of tumor sections grossly correlate with the redox images. The
      present work is the first to reveal at the submillimeter scale the intratumor
      heterogeneity pattern of the mitochondrial redox state in colon cancer and the
      first to indicate that at tissue level the mitochondrial redox state is p53
      dependent. The findings should assist in our understanding on colon cancer
      pathology and developing new imaging biomarkers for clinical applications.

PMID- 26207146
TI  - The ACCORD-Lipid study: implications for treatment of dyslipidemia in Type 2
      diabetes mellitus.
AB  - Patients with Type 2 diabetes mellitus (T2DM) are at high risk of developing
      cardiovascular disease (CVD). Treatment of diabetic dyslipidemia, comprised
      mainly of hypertriglyceridemia, and low HDL-C, with either statin or fibrate
      monotherapy, is moderately effective at reversing the abnormal lipid levels, but
      does not completely reverse the risk of CVD. Combination therapy with a statin
      and fibrate more effectively treats diabetic dyslipidemia; however, neither the
      impact on CVD risk nor the safety profile of statin-fibrate combined treatment
      had been tested in a large randomized trial. The Action to Control Cardiovascular
      Risk in Diabetes (ACCORD)-Lipid trial tested the hypothesis that combination
      therapy with a fibrate and statin would more effectively prevent major CVD events
      in a high-risk population of patients with T2DM compared with statin monotherapy.
      In ACCORD-Lipid, over 5000 patients were treated with fenofibrate plus
      simvastatin versus simvastatin alone. Although combination therapy did not
      significantly reduce CVD event rates in the ACCORD-Lipid cohort as a whole, a
      predefined subgroup of participants with the combination of significant
      hypertriglyceridemia and low HDL-C experienced a 31% lower event rate with
      combination therapy. Post hoc analyses conducted in similar subsets in previous
      fibrate monotherapy trials were concordant with these findings in ACCORD-Lipid.
      Combination therapy was well tolerated and safe, with no detectable increase in
      myopathy. The implications of the ACCORD-Lipid findings for the treatment of
      dyslipidemia in patients with T2DM are discussed.

PMID- 26207148
TI  - The role of short-term volunteers in a global health capacity building effort:
      the Project HOPE-GEMC experience.
AB  - BACKGROUND: Increasingly, medical students and practicing clinicians are showing
      interest in traveling to low-income settings to conduct research and engage in
      clinical rotations. While global health activities have the potential to benefit
      both the individual and the host, there can be challenges. We describe one way to
      harmonize the desire of volunteers to have a meaningful impact on the health care
      delivery system in a developing country with the needs of that country. METHODS:
      The Project Health Opportunities for People Everywhere (HOPE)-Ghana Emergency
      Medicine Collaborative (GEMC) Partnership has successfully integrated short-term
      volunteer physicians and nurses to facilitate the training of emergency medicine
      (EM) residents and specialist nurses in Kumasi, Ghana. RESULTS: Since the
      launching of this partnership in 2011, eight physicians and 10 nurses have
      rotated at Komfo Anokye Teaching Hospital (KATH). The impact of these volunteers
      goes beyond the clinical service and supervision they provide while on the
      ground. They act as mentors to the trainees and assist the program leadership
      with teaching and assessments. CONCLUSIONS: Although generally smooth, there have
      been challenges, all of which have been met and are being resolved. This
      partnership is an example of how collaborations can harness the expertise and
      energy of short-term volunteers to achieve the goals of capacity building and
      self-sustainability.

PMID- 26207149
TI  - Trends in mortality associated with opening of a full-capacity public emergency
      department at the main tertiary-level hospital in Tanzania.
AB  - BACKGROUND: Emergency medicine is an emerging specialty in Sub-Saharan Africa,
      and most hospitals do not have a fully functional emergency department (ED). We
      describe the mortality rates of the Muhimbili National Hospital (MNH) in Dar es
      Salaam, Tanzania before and after the opening of a full-capacity ED. METHODS:
      This retrospective study investigated ED and hospital mortality rates for
      patients admitted to MNH from January 2008 to January 2012. This period
      represents 2 years before and 2 years after the opening of the full-capacity ED
      in January 2010. Trained abstractors analyzed patient care logbooks, attendance
      registers, nurse report books, and death certificates. The January 2008 to
      December 2009 data are from the limited-capacity casualty room (precursor of the
      ED), and for February 2010 to January 2012, they are from the new ED. Data are
      presented as proportions or differences with 95 % confidence intervals (CIs).
      RESULTS: During the 4-year study period, the number of visits increased from
      53,660 (January 2008 to December 2009) in the casualty room to 77,164 (February
      2010 to January 2012) in the new ED. During this time, the overall hospital
      mortality rate decreased from 13.6 % (95 % CI 13.3-13.9 %) in the January 2008 to
      December 2009 period to 8.2 % (95 % CI 8.0-8.3 %) in the February 2010 to January
      2012 period. The corresponding casualty room and ED mortality rates were 0.34 %
      (95 % CI 0.25-0.35 %) and 0.74 % (95 % CI 0.68-0.80 %), respectively. In the
      casualty room, the most commonly reported cause of death was lower respiratory
      tract infection and least common was poisoning. In the new ED, the most commonly
      reported cause of death was congestive cardiac failure and the least common was
      cancer. CONCLUSIONS: The opening of a full-capacity ED in a tertiary-level
      hospital in sub-Saharan Africa was associated with a significant decrease in
      hospital mortality. This is despite a small, but significant, increase in the
      mortality rate in the ED as compared to that in the casualty room that it
      replaced.

PMID- 26207150
TI  - DNA hydroxymethylation age of human blood determined by capillary hydrophilic
      interaction liquid chromatography/mass spectrometry.
AB  - BACKGROUND: Aging is a complex phenomenon and characterized by a progressive
      decline in physiology and function of adult tissues. However, it hasn't been well
      established of the correlation between aging and global DNA methylation and
      hydroxymethylation that regulate the growth and development of higher organisms.
      RESULTS: We developed an on-line trapping/capillary hydrophilic-interaction
      liquid chromatography/electrospray ionization-mass spectrometry method for ultra
      sensitive and simultaneous quantification of 5-methylcytosine (5-mC) and 5
      hydroxymethylcytosine (5-hmC) in genomic DNA from human blood. Limits of
      detection for 5-mC and 5-hmC were 0.04 and 0.13 fmol, respectively. The
      imprecision and recovery of the method were determined with the relative standard
      deviations (RSDs) and relative errors being <11.2 and 14.0 %, respectively. We
      analyzed the contents of 5-mC and 5-hmC in genomic DNA of blood from 238 healthy
      people aged from 1 to 82 years. The results showed that 5-hmC content was
      significantly decreased and highly correlated with aging process, while 5-mC only
      showed slight correlation with age. We then established a DNA hydroxymethylation
      age model according to 5-hmC content with a mean absolute deviation (MAD) of
      approximate 8.9 years. We also calculated the mean relative error (MRE) using the
      predicted ages based on the age model and the chronological ages. The results
      showed that the MRE was 18.3 % for samples with ages from 20 to 82 years (95 %
      confidence interval, N = 190). CONCLUSIONS: The global DNA hydroxymethylation
      represents a strong and reproducible mark of chronological age, which could be
      potentially applied in health assessment and prevention of diseases. The
      identification of biological or environmental factors that influence DNA
      hydroxymethylation aging rate may permit quantitative assessments of their
      impacts on health.

PMID- 26207151
TI  - Genetic and epigenetic alterations of netrin-1 receptors in gastric cancer with
      chromosomal instability.
AB  - BACKGROUND: The gene expressions of netrin-1 dependence receptors, DCC and UNC5C,
      are frequently downregulated in many cancers. We hypothesized that downregulation
      of DCC and UNC5C has an important growth regulatory function in gastric
      tumorigenesis. RESULTS: In the present study, a series of genetic and epigenetic
      analyses for DCC and UNC5C were performed in a Japanese cohort of 98 sporadic
      gastric cancers and corresponding normal gastric mucosa specimens. Loss of
      heterozygosity (LOH) analyses and microsatellite instability (MSI) analysis was
      applied to determine chromosomal instability (CIN) and MSI phenotypes,
      respectively. More than 5 % methylation in the DCC and UNC5C promoters were found
      in 45 % (44/98) and 32 % (31/98) gastric cancers, respectively, and in 9 %
      (9/105) and 5 % (5/105) normal gastric mucosa, respectively. Overall, 70 % (58 of
      83 informative cases) and 51 % (40 of 79 informative cases) of gastric cancers
      harbored either LOH or aberrant methylation in the DCC and UNC5C genes,
      respectively. In total, 77 % (51 of 66 informative cases) of gastric cancers
      showed cumulative defects in these two dependence receptors and were
      significantly associated with chromosomal instability. Both DCC and UNC5C were
      inactivated in 97 % of CIN-positive gastric cancers and in 55 % of CIN-negative
      gastric cancers. CONCLUSIONS: Defect in netrin receptors is a common feature in
      gastric cancers. DCC alterations are apparent in the early stages, and UNC5C
      alterations escalate with the progression of the disease, suggesting that the
      cumulative alterations of netrin-1 receptors was a late event in gastric cancer
      progression and emphasizing the importance of this growth regulatory pathway in
      gastric carcinogenesis.

PMID- 26207152
TI  - Epigenetics override pro-inflammatory PTGS transcriptomic signature towards
      selective hyperactivation of PGE2 in colorectal cancer.
AB  - BACKGROUND: Misregulation of the PTGS (prostaglandin endoperoxide synthase, also
      known as cyclooxygenase or COX) pathway may lead to the accumulation of pro
      inflammatory signals, which constitutes a hallmark of cancer. To get insight into
      the role of this signaling pathway in colorectal cancer (CRC), we have
      characterized the transcriptional and epigenetic landscapes of the PTGS pathway
      genes in normal and cancer cells. RESULTS: Data from four independent series of
      CRC patients (502 tumors including adenomas and carcinomas and 222 adjacent
      normal tissues) and two series of colon mucosae from 69 healthy donors have been
      included in the study. Gene expression was analyzed by real-time PCR and
      Affymetrix U219 arrays. DNA methylation was analyzed by bisulfite sequencing,
      dissociation curves, and HumanMethylation450K arrays. Most CRC patients show
      selective transcriptional deregulation of the enzymes involved in the synthesis
      of prostanoids and their receptors in both tumor and its adjacent mucosa. DNA
      methylation alterations exclusively affect the tumor tissue (both adenomas and
      carcinomas), redirecting the transcriptional deregulation to activation of
      prostaglandin E2 (PGE2) function and blockade of other biologically active
      prostaglandins. In particular, PTGIS, PTGER3, PTGFR, and AKR1B1 were
      hypermethylated in more than 40 % of all analyzed tumors. CONCLUSIONS: The
      transcriptional and epigenetic profiling of the PTGS pathway provides important
      clues on the biology of the tumor and its microenvironment. This analysis renders
      candidate markers with potential clinical applicability in risk assessment and
      early diagnosis and for the design of new therapeutic strategies.

PMID- 26207153
TI  - Expertise, Working Memory and Articulatory Suppression Effect: Their Relation
      with Simultaneous Interpreting Performance.
AB  - Simultaneous interpreting is a complex bilingual verbal activity that involves
      the auditory perception of an oral communication and the production of a coherent
      discourse. One of the cognitive functions underlying simultaneous interpreting is
      working memory. The aim of this work was to study the relationship between
      expertise, working memory capacity and articulatory suppression effect, and the
      ability to perform simultaneous interpreting. For this purpose, four working
      memory tasks and one simultaneous interpreting task were administered to thirty
      Spanish-speaking professional English interpreters. Results showed that
      simultaneous interpreting ability might be supported by the working memory's
      capacity to store or process information, but also by the ability of the
      interpreter to cope with the articulatory suppression effect. We conclude that
      interpreters may have or develop resources to support the effect caused by
      articulatory suppression. 

PMID- 26207155
TI  - Minute pollinators: The role of thrips (Thysanoptera) as pollinators of pointleaf
      manzanita, Arctostaphylos pungens (Ericaceae).
AB  - The feeding habits of thrips on plant tissue, and their ability to transmit viral
      diseases to their host plants, have usually placed these insects in the general
      category of pests. However, the characteristics that make them economically
      important, their high abundance and short- and long-distance movement capability,
      may also make them effective pollinators. We investigated this lesser-known role
      of thrips in pointleaf manzanita (Arctostaphylos pungens), a Southwestern US
      shrub. We measured the abundance of three species of thrips (Orothrips kelloggii,
      Oligothrips oreios, and Frankliniella occidentalis), examined their pollen
      carrying capability, and conducted an exclusion experiment in order to determine
      whether thrips are able to pollinate this species, and if they do, whether they
      actually contribute to the reproductive success of the plant. Our data suggest
      that indeed thrips pollinate and do contribute significantly to reproductive
      success. Flowers exposed to thrips only produced significantly more fruit than
      did flowers from which all visitors were excluded. The roles of thrips as
      antagonists/mutualists are examined in the context of the numerous other floral
      visitors to the plant.

PMID- 26207156
TI  - Predicting Use of Ineffective Responsive, Structure and Control Vegetable
      Parenting Practices with the Model of Goal Directed Behavior.
AB  - This study reports the modeling of three categories of ineffective vegetable
      parenting practices (IVPP) separately (responsive, structure, and control
      vegetable parenting practices). An internet survey was employed for a cross
      sectional assessment of parenting practices and cognitive-emotional variables.
      Parents (n=307) of preschool children (3-5 years old) were recruited through
      announcements and postings. Models were analyzed with block regression and
      backward deletion procedures using a composite IVPP scale as the dependent
      variable. The independent variables included validated scales from a Model of
      Goal Directed Vegetable Parenting Practices (MGDVPP), including: intention,
      habit, perceived barriers, desire, competence, autonomy, relatedness, attitudes,
      norms, perceived behavioral control, and anticipated emotions. The available
      scales accounted for 26.5%, 16.7% and 44.6% of the variance in the IVPP
      responsive, structure and control subscales, respectively. Different sets of
      diverse variables predicted the three IVPP constructs. Intentions, Habits and
      Perceived Behavioral Control were strong predictors for each of the IVPP
      constructs, but the subscales were specific to each IVPP construct. Parent
      emotional responses, an infrequently investigated variable, was an important
      predictor of ineffective responsive vegetable parenting practices and ineffective
      structure vegetable parenting practices, but not ineffective control vegetable
      parenting practices. An Attitude subscale and a Norms subscale predicted
      ineffective responsive vegetable parenting practices alone. This was the first
      report of psychometrically tested scales to predict use of IVPP subscales.
      Further research is needed to verify these findings in larger longitudinal
      cohorts. Interventions to increase child vegetable intake may have to reduce
      IVPP.

PMID- 26207154
TI  - Experimental Divergences in the Visual Cognition of Birds and Mammals.
AB  - The comparative analysis of visual cognition across classes of animals yields
      important information regarding underlying cognitive and neural mechanisms
      involved with this foundational aspect of behavior. Birds, and pigeons
      specifically, have been an important source and model for this comparison,
      especially in relation to mammals. During these investigations, an extensive
      number of experiments have found divergent results in how pigeons and humans
      process visual information. Four areas of these divergences are collected,
      reviewed, and analyzed. We examine the potential contribution and limitations of
      experimental, spatial, and attentional factors in the interpretation of these
      findings and their implications for mechanisms of visual cognition in birds and
      mammals. Recommendations are made to help advance these comparisons in service of
      understanding the general principles by which different classes and species
      generate representations of the visual world.

PMID- 26207157
TI  - Studying the Effects of Cysteine Residues on Protein Interactions with Silver
      Nanoparticles.
AB  - Studies of protein and organothiol interactions with silver nanoparticles (AgNPs)
      are important for understanding AgNP nanotoxicity, antimicrobial activity, and
      material fabrications. Reported herein is a systematic investigation of the
      effects of both reduced and oxidized protein cysteine residues on protein
      interactions with AgNPs. The model proteins included wild-type and mutated
      protein GB3 variants that contain 0, 1, or 2 reduced cysteine residues,
      respectively. Bovine serum albumin (BSA) that contains a total of 34 oxidized
      (disulfide-linked) cysteine residues and one reduced cysteine residue was also
      included. Protein cysteine content has no detectable effect on the kinetics of
      protein/AgNP binding. However, only proteins that contain reduced cysteine
      residues induce significant AgNP dissolution. Proteins can slow down, but do not
      prevent the AgNP dissolution induced by subsequently added organothiols. The
      insights provided in this work are important to the mechanistic understanding of
      AgNP stability in biofluids that are rich in proteins and amino acid thiols.

PMID- 26207158
TI  - Distributional Analysis in Educational Evaluation: A Case Study from the New York
      City Voucher Program.
AB  - We use quantile treatment effects estimation to examine the consequences of the
      random-assignment New York City School Choice Scholarship Program (NYCSCSP)
      across the distribution of student achievement. Our analyses suggest that the
      program had negligible and statistically insignificant effects across the skill
      distribution. In addition to contributing to the literature on school choice, the
      paper illustrates several ways in which distributional effects estimation can
      enrich educational research: First, we demonstrate that moving beyond a focus on
      mean effects estimation makes it possible to generate and test new hypotheses
      about the heterogeneity of educational treatment effects that speak to the
      justification for many interventions. Second, we demonstrate that distributional
      effects can uncover issues even with well-studied datasets by forcing analysts to
      view their data in new ways. Finally, such estimates highlight where in the
      overall national achievement distribution test scores of children exposed to
      particular interventions lie; this is important for exploring the external
      validity of the intervention's effects.

PMID- 26207159
TI  - Molecular, proteomic and immunological parameters of allergens provide inclusion
      criteria for new candidates within established grass and tree homologous groups.
AB  - BACKGROUND: Our knowledge of allergen structure and function continues to rise
      and new scientific data on the homology and cross-reactivity of allergen sources
      should be considered to extend the work of Lorenz et al., 2009 (Int Arch Allergy
      Immunol. 148(1):1-1, 2009) and the concept of homologous groups. In addition to
      this, sophisticated techniques such as mass spectrometry (MS) are increasingly
      utilised to better characterise the complex mix and nature of allergen extracts.
      METHODS: Homology models were used of Fag s 1 (Beech) and Cyn d 1 (Bermuda grass)
      and compared with template crystal structures of Bet v 1 and Phl p 1 from the
      'exemplar' species of Birch and Timothy grass, respectively. ELISA experiments
      were performed to assess cross-reactivity of Beech (tree) and Bermuda (grass)
      extracts to rabbit sera raised to either "3-Tree" (Birch, Alder and Hazel)
      extract or "Grass" (12-grass mix extract), respectively. The comparability of
      biochemical stability of different allergen sources was assessed through
      statistical methods for a range of tree and grass species. RESULTS: Allergen
      cross-reactivity and/or structural homology have been described providing
      justification for inclusion of Beech within the Birch homologous tree group. Data
      from Bermuda grass (Cyn d 1) provides further justification for the inclusion of
      this species into the homologous group of the sweet grasses. However, further
      characterisation of relevant allergens from Bermuda grass and, in particular,
      comparison of cross-reactive patterns between subjects specifically in areas with
      high abundance of both Pooideae and Chloridoideae is sought. CONCLUSION: MS
      allows the possibility to identify individual proteins or allergens from complex
      mixes by mass and/or sequence, and this has been extensively applied to the
      allergen field. New data on the homology, cross-reactivity and biological
      parameters of allergen sources have been considered to extend the work of Lorenz
      et al., 2009 in the context of tree and grass species. The concept of homologous
      groups is certainly dynamic allowing the flexibility and potential in
      streamlining quality parameters, such as stability profiles, due to extrapolation
      of exemplar data to a wider range of allergens.

PMID- 26207161
TI  - 1pPAb5. Acoustic radiation force to reposition kidney stones.
AB  - Our group has introduced transcutaneous ultrasound to move kidney stones in order
      to expel small stones or relocate an obstructing stone to a nonobstructing
      location. Human stones and metalized beads (2-8 mm) were implanted
      ureteroscopically in kidneys of eight domestic swine. Ultrasonic propulsion was
      performed using a diagnostic imaging transducer and a Verasonics ultrasound
      platform. Stone propulsion was visualized using fluoroscopy, ultrasound, and the
      ureteroscope. Successful stone movement was defined as relocating a stone to the
      renal pelvis, ureteropelvic junction (UPJ) or proximal ureter. Three blinded
      experts evaluated for histologic injury in control and treatment arms. All stones
      were moved. 65% (17/26) of stones/beads were moved the entire distance to the
      renal pelvis (3), UPJ (2), or ureter (12). Average successful procedure per stone
      required 14+/-8 min and 23+/-16 pushes. Each push averaged 0.9 s in duration.
      Mean interval between pushes was 41+/-13 sec. No gross or histologic kidney
      damage was identified in six kidneys from exposure to 20 1-s pushes spaced by 33
      s. Ultrasonic propulsion is effective with most stones being relocated to the
      renal pelvis, UPJ, or ureter. The procedure appears safe without evidence of
      injury.

PMID- 26207162
TI  - Hepatic metastatic disease in pediatric and adolescent solid tumors.
AB  - The management of hepatic metastatic disease from solid tumors in adults has been
      extensively described and resection of metastatic liver lesions from colorectal
      adenocarcinoma, renal adenocarcinoma, breast cancer, testicular cancer, and
      neuroendocrine tumors (NET) have demonstrated therapeutic benefits in select
      patients. However, there are few reports in the literature on the management of
      hepatic metastatic disease in the pediatric and adolescent populations and the
      effectiveness of hepatic metastasectomy. This may be due to the much lower
      incidence of pediatric malignancies and the higher chemosensitivity of childhood
      tumors which make hepatic metastasectomy less likely to be required. We review
      liver involvement with metastatic disease from the main pediatric solid tumors,
      including neuroblastoma and Wilms tumor focusing on the management and treatment
      options. We also review other solid malignant tumors which may have liver
      metastases including germ cell tumors, gastrointestinal stromal tumors,
      osteosarcoma, desmoplastic small round cell tumors and NET. However, these
      histological subtypes are so rare in the pediatric and adolescent populations
      that the exact incidence and best management of hepatic metastatic disease are
      unknown and can only be extrapolated from adult series. 

PMID- 26207163
TI  - Spontaneous bleeding or thrombosis in cirrhosis: What should be feared the most?
AB  - The more modern and accurate concept of a rebalanced hemostatic status in
      cirrhosis is slowly replacing the traditional belief of patients with cirrhosis
      being "auto-anticoagulated", prone only to bleeding complications, and protected
      from thrombotic events. With greater attention to clinical thrombotic events,
      their impact on the natural history of cirrhosis, and with the emergence and
      increased use of point-of-care and global assays, it is now understood that
      cirrhosis results in profound hemostatic alterations that can lead to thrombosis
      as well as to bleeding complications. Although many clinical decisions are still
      based on traditional coagulation parameters such as prothrombin (PT), PT, and
      international normalized ratio, it is increasingly recognized that these tests do
      not adequately predict the risk of bleeding, nor they should guide pre-emptive
      interventions. Moreover, altered coagulation tests should not be considered as a
      contraindication to the use of anticoagulation, although this therapeutic or
      prophylactic approach is not at present routinely undertaken. Gastroesophageal
      variceal bleeding continues to be one of the most feared and deadly complications
      of cirrhosis and portal hypertension, but great progresses have been made in
      prevention and treatment strategies. Other bleeding sites that are frequently
      part of end-stage liver disease are similar to clinical manifestations of
      thrombocytopenia, with gum bleeding and epistaxis being very common but
      fortunately only rarely a cause of life-threatening bleeding. On the contrary,
      manifestations of coagulation factor deficiencies like soft tissue bleeding and
      hemartrosis are rare in patients with cirrhosis. As far as thrombotic
      complications are concerned, portal vein thrombosis is the most common event in
      patients with cirrhosis, but venous thromboembolism is not infrequent, and
      results in important morbidity and mortality in patients with cirrhosis,
      especially those with decompensated disease. Future studies and the more
      widespread use of point-of-care tests in evaluating hemostasis will aid the
      clinician in decision making when facing the patient with bleeding or with
      thrombotic complications, with both ends of a continuum being potentially fatal. 

PMID- 26207164
TI  - Voriconazole and the liver.
AB  - Voriconazole is an azole useful for the prophylaxis and the treatment of
      aspergillosis and other fungal infections in immunosuppressed subjects, as those
      found in aplasia after aggressive polychemotherapy treatments, after
      hematopoietic stem cell, liver or lung transplantation. Its administration in
      therapeutic doses lead to extremely varied serum levels from patient to patient
      and even to the same patient. The explanations are varied: nonlinear
      pharmacokinetics, certain patient-related factors, including genetic
      polymorphisms in the cytochrome P450 2C19 gene, the kidney and liver function,
      simultaneous administration with other drugs metabolised by the same cytochrome.
      It is recommended to maintain the serum concentrations of voriconazole between
      1.5 and 4 MUg/mL. At lower values its efficacy decreases and at higher values the
      risk of neurological toxicity increases. Even at these concentrations it is not
      excluded the possible appearance of a variety of toxic effects, including on the
      liver, manifested by cholestasis, hepatocytolisis, or their combination. It is
      recommended to monitor the clinical and laboratory evolution of all patients
      treated with voriconazole, and of the serum levels of the drug of those who
      belong to risk groups, even if there is still no consensus on this issue, given
      the lack of correlation between the serum level and the occurrence of adverse
      effects in many patients. 

PMID- 26207165
TI  - Circulating biomarkers of hepatocellular carcinoma response after locoregional
      treatments: New insights.
AB  - Hepatocellular cancer is the 5(th) most common cancer in the world and the third
      cause of death by malignant disease. Locoregional therapies are the most usual
      treatment of choice for patients with early or intermediate stage of disease. The
      main diagnostic tools for the detection of recurrence are the radiological
      techniques such as 4-phase computed tomography or dynamic contrast enhanced
      magnetic resonance imaging. However, in order to achieve best evaluation of
      treatment outcome and recurrence rates, there is a great need for the
      identification of specific and easily measured circulating biomarkers. The aim of
      this review is to analyze the existing data considering the prognostic
      significance of changes of serum diagnostic markers such as alpha-fetoprotein,
      des-gamma-carboxy prothrombin, alpha-fetoprotein-L3, angiogenetic factors
      (vascular endothelial growth factor, hypoxia inducible factor-1a) and immune
      parameters before and after radiofrequency ablation or transarterial
      chemoembolization. 

PMID- 26207166
TI  - Hepatitis C cirrhosis: New perspectives for diagnosis and treatment.
AB  - Chronic hepatitis C infection is the leading cause of chronic liver disease,
      cirrhosis, hepatocellular carcinoma as well as the primary indication for liver
      transplantation in the United States. Despite recent advances in drugs for the
      treatment of hepatitis C, predictive models estimate the incidence of cirrhosis
      due to hepatitis C infection will to continue to rise for the next two decades.
      There is currently an immense interest in the treatment of patients with fibrosis
      and early-stage cirrhosis as treatment can lead to decrease in the rates of
      decompensated cirrhosis, hepatocellular carcinoma and need for liver
      transplantation in these patients. The goal of this paper is to provide
      clinicians and health care professionals further information about the treatment
      of patients with hepatitis C infection and cirrhosis. Additionally, the paper
      focuses on the disease burden, epidemiology, diagnosis and the disease course
      from infection to treatment. We provide an overview of multiple studies for the
      treatment of chronic hepatitis C infection that have included patients with
      cirrhosis. We also discuss the advantages and disadvantages of treatment in
      cirrhotic patients and focus on the most up to date guidelines available for
      treatment. 

PMID- 26207160
TI  - Meteorological conditions, climate change, new emerging factors, and asthma and
      related allergic disorders. A statement of the World Allergy Organization.
AB  - The prevalence of allergic airway diseases such as asthma and rhinitis has
      increased dramatically to epidemic proportions worldwide. Besides air pollution
      from industry derived emissions and motor vehicles, the rising trend can only be
      explained by gross changes in the environments where we live. The world economy
      has been transformed over the last 25 years with developing countries being at
      the core of these changes. Around the planet, in both developed and developing
      countries, environments are undergoing profound changes. Many of these changes
      are considered to have negative effects on respiratory health and to enhance the
      frequency and severity of respiratory diseases such as asthma in the general
      population. Increased concentrations of greenhouse gases, and especially carbon
      dioxide (CO2), in the atmosphere have already warmed the planet substantially,
      causing more severe and prolonged heat waves, variability in temperature,
      increased air pollution, forest fires, droughts, and floods - all of which can
      put the respiratory health of the public at risk. These changes in climate and
      air quality have a measurable impact not only on the morbidity but also the
      mortality of patients with asthma and other respiratory diseases. The massive
      increase in emissions of air pollutants due to economic and industrial growth in
      the last century has made air quality an environmental problem of the first order
      in a large number of regions of the world. A body of evidence suggests that major
      changes to our world are occurring and involve the atmosphere and its associated
      climate. These changes, including global warming induced by human activity, have
      an impact on the biosphere, biodiversity, and the human environment. Mitigating
      this huge health impact and reversing the effects of these changes are major
      challenges. This statement of the World Allergy Organization (WAO) raises the
      importance of this health hazard and highlights the facts on climate-related
      health impacts, including: deaths and acute morbidity due to heat waves and
      extreme meteorological events; increased frequency of acute cardio-respiratory
      events due to higher concentrations of ground level ozone; changes in the
      frequency of respiratory diseases due to trans-boundary particle pollution;
      altered spatial and temporal distribution of allergens (pollens, molds, and
      mites); and some infectious disease vectors. According to this report, these
      impacts will not only affect those with current asthma but also increase the
      incidence and prevalence of allergic respiratory conditions and of asthma. The
      effects of climate change on respiratory allergy are still not well defined, and
      more studies addressing this topic are needed. Global warming is expected to
      affect the start, duration, and intensity of the pollen season on the one hand,
      and the rate of asthma exacerbations due to air pollution, respiratory
      infections, and/or cold air inhalation, and other conditions on the other hand. 

PMID- 26207167
TI  - Spectrum of biliary complications following live donor liver transplantation.
AB  - Liver transplantation is the optimal treatment for many patients with advanced
      liver disease, including decompensated cirrhosis, hepatocellular carcinoma and
      acute liver failure. Organ shortage is the main determinant of death on the
      waiting list and hence living donor liver transplantation (LDLT) assumes
      importance. Biliary complications are the most common post operative morbidity
      after LDLT and occur due to anatomical and technical reasons. They include
      biliary leaks, strictures and cast formation and occur in the recipient as well
      as the donor. The types of biliary complications after LDLT along with their
      etiology, presenting features, diagnosis and endoscopic and surgical management
      are discussed. 

PMID- 26207168
TI  - Usefulness of contrast enhanced ultrasound in monitoring therapeutic response
      after hepatocellular carcinoma treatment.
AB  - In the last years, the development in the oncology field has been huge and rapid.
      In particular, the evaluation of response to anti-tumour treatments has been
      being object of intense research, producing significant changes. Response
      assessment after therapy in solid neoplasias has always used radiological imaging
      techniques, with tumour size reduction representing a presumed therapeutic
      efficacy. However, with the introduction of anti-angiogenetic drugs the
      evaluation of tumour size has become unsuitable because some tumours, under
      treatment, show only tumour perfusion changes rather than lesion shrinkage.
      Between different imaging techniques with contrast-enhancement, contrast-enhanced
      ultrasound (CEUS) and, in particular, dynamic CEUS have arisen as a promising and
      non-invasive device for monitoring cancer treatments. Moreover, the introduction
      of perfusion software has even more refined the technique since it is able to
      provide quantitative parameters related to blood flow and blood volume that can
      be associated with tumour response and clinical outcome such as the progression
      free survival and the overall survival. Here, we give an overview of the current
      status of CEUS in monitoring hepatocellular carcinoma response to different kind
      of treatments. 

PMID- 26207170
TI  - Utility of liver biopsy in predicting clinical outcomes after percutaneous
      angioplasty for hepatic venous obstruction in liver transplant patients.
AB  - AIM: To determine utility of transplant liver biopsy in evaluating efficacy of
      percutaneous transluminal angioplasty (PTA) for hepatic venous obstruction
      (HVOO). METHODS: Adult liver transplant patients treated with PTA for HVOO (2003
      2013) at a single institution were reviewed for pre/post-PTA imaging findings,
      manometry (gradient with right atrium), presence of HVOO on pre-PTA and post-PTA
      early and late biopsy (EB and LB, < or > 60 d after PTA), and clinical outcome,
      defined as good (no clinical issues, non-HVOO-related death) or poor (surgical
      correction, recurrent HVOO, or HVOO-related death). RESULTS: Fifteen patients
      meeting inclusion criteria underwent 21 PTA, 658 +/- 1293 d after transplant. In
      procedures with pre-PTA biopsy (n = 19), no difference was seen between pre-PTA
      gradient in 13/19 procedures with HVOO on biopsy and 6/19 procedures without HVOO
      (8 +/- 2.4 mmHg vs 6.8 +/- 4.3 mmHg; P = 0.35). Post-PTA, 10/21 livers had EB (29
      +/- 21 d) and 9/21 livers had LB (153 +/- 81 d). On clinical follow-up (392 +/-
      773 d), HVOO on LB resulted in poor outcomes and absence of HVOO on LB resulted
      good outcomes. Patients with HVOO on EB (3/7 good, 4/7 poor) and no HVOO on EB
      (2/3 good, 1/3 poor) had mixed outcomes. CONCLUSION: Negative liver biopsy
      greater than 60 d after PTA accurately identifies patients with good clinical
      outcomes.

PMID- 26207169
TI  - Cartilage oligomeric matrix protein: A novel non-invasive marker for assessing
      cirrhosis and risk of hepatocellular carcinoma.
AB  - AIM: To assess serum cartilage oligomeric matrix protein (COMP) as a marker of
      cirrhosis and risk of progression to hepatocellular carcinoma (HCC). METHODS: A
      COMP enzyme-linked immunosorbent assay was used to test 187 patients with chronic
      liver diseases at the time point of first evaluation. The selected patients
      included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C
      infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1,
      and 11 with alcoholic liver disease. Demographic, biochemical, histological and
      clinical characteristics of the patients were recorded at the first evaluation.
      One hundred and forty-seven patients were followed for a median [interquartile
      range (IQR)] duration of 96.5 (102) mo. The clinical, biochemical and
      histological data, as well as the development of cirrhosis, HCC according to
      internationally accepted criteria and in case of death, a liver-related cause
      during the follow-up period, were recorded at the electronic database of our
      clinic. COMP determination was also performed in 43 healthy individuals who
      served as the control study group. RESULTS: COMP positivity (> 15 U/L) was
      detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of
      COMP-positive patients were cirrhotic at baseline, independently of cause of
      liver disease. Among the patients who developed HCC during follow-up, 73.7%
      (14/19) were COMP positive at baseline. COMP positivity was significantly
      associated with older age (P < 0.001), advanced fibrosis (P = 0.001) and
      necroinflammatory activity (P = 0.001), higher aspartate aminotransferase (P <
      0.001), alanine aminotransferase (P < 0.02), gamma-glutamyl transpeptidase (P =
      0.003), alkaline phosphatase (P = 0.001), bilirubin (P < 0.05), international
      normalized ratio (P = 0.002) and alpha-fetoprotein levels (P < 0.02), and lower
      albumin (P < 0.001), and platelet count (P = 0.008). COMP levels [median (IQR)]
      were significantly higher in cirrhotics compared to non-cirrhotics [13.8 (7.9)
      U/L vs 9.8 (4.6) U/L, respectively; P < 0.001]. On multivariate logistic
      regression analysis, COMP-positivity was independently associated only with
      cirrhosis (OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed
      that COMP positivity was significantly associated with HCC development (P =
      0.007) and higher incidence of liver-related death (P < 0.001). CONCLUSION:
      Elevated COMP levels are strongly associated with cirrhosis and HCC progression.
      Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in
      surveillance programs.

PMID- 26207171
TI  - Dynamic Equilibria of Short-Range Electrostatic Interactions at Molecular
      Interfaces of Protein-DNA Complexes.
AB  - Intermolecular ion pairs (salt bridges) are crucial for protein-DNA association.
      For two protein-DNA complexes, we demonstrate that the ion pairs of protein side
      chain NH3+ and DNA phosphate groups undergo dynamic transitions between distinct
      states in which the charged moieties are either in direct contact or separated by
      water. While the crystal structures of the complexes show only the solvent
      separated ion pair (SIP) state for some interfacial lysine side chains, our NMR
      hydrogen-bond scalar coupling data clearly indicate the presence of the contact
      ion pair (CIP) state for the same residues. The 0.6-MUs molecular dynamics (MD)
      simulations confirm dynamic transitions between the CIP and SIP states. This
      behavior is consistent with our NMR order parameters and scalar coupling data for
      the lysine side chains. Using the MD trajectories, we also analyze the free
      energies of the CIP-SIP equilibria. This work illustrates the dynamic nature of
      short-range electrostatic interactions in DNA recognition by proteins.

PMID- 26207172
TI  - Anomalous Behavior of the Homogeneous Ice Nucleation Rate in "No-Man's Land".
AB  - We present an analysis of ice nucleation kinetics from near-ambient pressure
      water as temperature decreases below the homogeneous limit TH by cooling
      micrometer-sized droplets (microdroplets) evaporatively at 103-104 K/s and
      probing the structure ultrafast using femtosecond pulses from the Linac Coherent
      Light Source (LCLS) free-electron X-ray laser. Below 232 K, we observed a slower
      nucleation rate increase with decreasing temperature than anticipated from
      previous measurements, which we suggest is due to the rapid decrease in water's
      diffusivity. This is consistent with earlier findings that microdroplets do not
      crystallize at <227 K, but vitrify at cooling rates of 106-107 K/s. We also
      hypothesize that the slower increase in the nucleation rate is connected with the
      proposed "fragile-to-strong" transition anomaly in water.

PMID- 26207173
TI  - Risk and Protective Factors for Lifetime Marijuana Use among Colombian Emergent
      Adults Attending College.

PMID- 26207174
TI  - All the right moves: the need for the timely use of hyperbaric oxygen therapy for
      treating TBI/CTE/PTSD.
AB  - BACKGROUND: The modern age of hyperbaric medicine began in 1937; however, today
      few know about hyperbaric oxygen's effects on the body and medical conditions
      outside of diving medicine and wound care centers - a serious ethical issue as
      there are 20 US military veterans committing suicide every day directly related
      to Traumatic Brain Injury/Post Traumatic Stress Disorder. The problem is not
      whether hyperbaric oxygen is effective for treating brain injuries, but why the
      interference in offering this therapy to those who need it. DISCUSSION: Up
      against black-boxed anti-depressants that are not efficacious, it should be a "no
      brainer" to use a safe, off-label drug, but in the case of military veterans,
      every suicide might be seen as a tremendous cost saving to certain technocrats.
      The unspoken rationale is that if the military were to embrace hyperbaric oxygen
      as the efficacious therapy that it is then current active troops that have
      suffered injuries will come forward and seek treatment and benefits for their
      Traumatic Brain Injuries now that they know there is a viable therapy and in so
      doing troop strength will be decimated. So, to attempt to delay the acceptance of
      hyperbaric oxygen the Department of Defense has funded faux-studies claiming low
      pressure room air to be a placebo or sham, and then proclaiming there is no
      statistical difference between treatment arms and sham or placebo treatment arms.
      With few who understand hyperbaric medicine there is almost no one to call them
      on this subterfuge and prevarication. Many peer-reviewed articles have been
      published in the last decade that demonstrate hyperbaric oxygen is effective in
      repairing an injured brain even long after that injury took place. One of the
      most notable showed that blast-induced brain injured war veterans experienced a
      15 point IQ increase (p < 0.001). SUMMARY: Hyperbaric oxygen is an efficacious,
      benign and humanitarian way to affect brain repair but it has not been adopted
      because it lacks patent protection and has no large corporate sponsors. It has
      also met interference because other agendas are present be they the protection of
      the status quo, myopic budgetary constraints, or perceived liability issues.

PMID- 26207176
TI  - Better reporting for better research: a checklist for reproducibility.

PMID- 26207175
TI  - Myocardial functional responses do not contribute to maximal exercise performance
      in the heat.
AB  - BACKGROUND: Both the extent and means by which maximal oxygen uptake ([Formula:
      see text]) is depressed by elevated ambient temperature are uncertain.
      Particularly, information is currently unavailable regarding the possible
      influence of alterations in myocardial function on [Formula: see text] and
      performance during exercise in the heat. This study investigated the effects of
      environmental heat on [Formula: see text], peak work capacity, and myocardial
      function during a standard, progressive cycle test to exhaustion. Twelve
      euhydrated men (aged 20.7 +/- 1.7 years) performed a maximal cycle test in an
      environmental chamber in both heat stress [35 degrees C, 30% relative humidity
      (RH)] and temperate (20 degrees C, 30% RH) conditions with measurement of
      standard gas exchange variables, core temperature, and echocardiographic measures
      of cardiac function. RESULTS: A small but statistically significant reduction of
      peak work capacity was observed in the heat stress versus temperate conditions
      (253 +/- 30 and 259 +/- 30 W, respectively, p = 0.02). Mean [Formula: see text]
      was not statistically different in the two conditions (p = 0.16) but values were
      3.4% lower in the heat, and 9 of 12 participants demonstrated lower values in the
      heat stress trial. No differences in responses of heart rate, cardiac output,
      stroke volume, core temperature, hydration status, or myocardial systolic or
      diastolic function were observed between the two conditions, but perceived body
      temperature was higher in the heat. CONCLUSIONS: The small, negative impact of
      heat on exercise performance and [Formula: see text] could not be explained by
      disturbances in myocardial functional responses to exercise in young adult males.

PMID- 26207177
TI  - Providing nursing care to Ebola virus disease patients: China Ebola Treatment
      Unit experience.

PMID- 26207178
TI  - Adverse effects of political sanctions on the health care system in Iran.

PMID- 26207179
TI  - Why are girls still dying unnecessarily? The need to address gender inequity in
      child health in the post-2015 development agenda.

PMID- 26207180
TI  - Remoteness and maternal and child health service utilization in rural Liberia: A
      population-based survey.
AB  - BACKGROUND: This study seeks to understand distance from health facilities as a
      barrier to maternal and child health service uptake within a rural Liberian
      population. Better understanding the relationship between distance from health
      facilities and rural health care utilization is important for post-Ebola health
      systems reconstruction and for general rural health system planning in sub
      Saharan Africa. METHODS: Cluster-sample survey data collected in 2012 in a very
      rural southeastern Liberian population were analyzed to determine associations
      between quartiles of GPS-measured distance from the nearest health facility and
      the odds of maternal (ANC, facility-based delivery, and PNC) and child (deworming
      and care seeking for ARI, diarrhea, and fever) service use. We estimated
      associations by fitting simple and multiple logistic regression models, with
      standard errors adjusted for clustered data. FINDINGS: Living in the farthest
      quartile was associated with lower odds of attending 1-or-more ANC checkup (AOR =
      0.04, P < 0.001), 4-or-more ANC checkups (AOR = 0.13, P < 0.001), delivering in a
      facility (AOR = 0.41, P = 0.006), and postnatal care from a health care worker
      (AOR = 0.44, P = 0.009). Children living in all other quartiles had lower odds of
      seeking facility-based fever care (AOR for fourth quartile = 0.06, P < 0.001)
      than those in the nearest quartile. Children in the fourth quartile were less
      likely to receive deworming treatment (AOR = 0.16, P < 0.001) and less likely
      (but with only marginal statistical significance) to seek ARI care from a formal
      HCW (AOR = 0.05, P = 0.05). Parents in distant quartiles more often sought ARI
      and diarrhea care from informal providers. CONCLUSIONS: Within a rural Liberian
      population, distance is associated with reduced health care uptake. As Liberia
      rebuilds its health system after Ebola, overcoming geographic disparities,
      including through further dissemination of providers and greater use of community
      health workers should be prioritized.

PMID- 26207181
TI  - Association between HRP-2/pLDH rapid diagnostic test band positivity and malaria
      related anemia at a peripheral health facility in Western Uganda.
AB  - The detection of severe malaria in resource-constrained settings is often
      difficult because of requirements for laboratory infrastructure and/or clinical
      expertise. The aim of this study, therefore, was to explore the utility of a
      multiple antigen (HRP-2/pLDH) rapid diagnostic test (RDT) as a low-cost,
      surrogate marker of patients at high risk for complications of severe malaria. We
      reviewed programmatic data at a peripheral health center in Western Uganda.
      Available demographic and clinical data on all individuals presenting to the
      center who underwent an RDT for suspected malaria infection were reviewed. We fit
      logistic regression models to identify correlates of two outcomes of interest: 1)
      severe malaria-related anemia, defined here as hemoglobin <=7g/dL and 2) receipt
      of parenteral quinine. 1509 patients underwent malaria testing with an SD FK60
      RDT during the observation period. A total of 637 (42%) RDTs were positive for at
      least one species of malaria, of which 326 (51%) exhibited a single HRP-2 band
      and 307 (48%) exhibited both HRP-2 and pLDH bands, while 4 exhibited only a
      single pLDH band. There was a trend towards more severe anemia in patients with a
      HRP-2/pLDH positive RDT compared to a HRP-2 only RDT (beta = -0.99 g/dl, 95% CI 
      1.99 to 0.02, P = 0.055). A HRP-2/pLDH positive RDT was associated with an
      increased risk of severe malaria-related anemia compared to a negative RDT
      (adjusted odds ratio (AOR) 18.8, 95% CI 4.32 to 82.0, P < 0.001) and to a HRP-2
      only RDT (AOR 2.46, 95% CI 0.75 to 8.04, P = 0.14). There was no significant
      association between RDT result and the administration of parenteral quinine.
      These results offer preliminary evidence that specific patterns of antigen
      positivity on RDTs could be utilized to identify patients at an increased risk
      for complications of severe malaria. 

PMID- 26207183
TI  - Erratum: Gut resistome development in healthy twin pairs in the first year of
      life.
AB  - [This corrects the article DOI: 10.1186/s40168-015-0090-9.]. 

PMID- 26207182
TI  - Characteristics of lipids and their feeding value in swine diets.
AB  - In livestock diets, energy is one of the most expensive nutritional components of
      feed formulation. Because lipids are a concentrated energy source, inclusion of
      lipids are known to affect growth rate and feed efficiency, but are also known to
      affect diet palatability, feed dustiness, and pellet quality. In reviewing the
      literature, the majority of research studies conducted on the subject of lipids
      have focused mainly on the effects of feeding presumably high quality lipids on
      growth performance, digestion, and metabolism in young animals. There is,
      however, the wide array of composition and quality differences among lipid
      sources available to the animal industry making it essential to understand
      differences in lipid composition and quality factors affecting their digestion
      and metabolism more fully. In addition there is often confusion in lipid
      nomenclature, measuring lipid content and composition, and evaluating quality
      factors necessary to understand the true feeding value to animals. Lastly,
      advances in understanding lipid digestion, post-absorption metabolism, and
      physiological processes (e.g., cell division and differentiation, immune function
      and inflammation); and in metabolic oxidative stress in the animal and lipid
      peroxidation, necessitates a more compressive assessment of factors affecting the
      value of lipid supplementation to livestock diets. The following review provides
      insight into lipid classification, digestion and absorption, lipid peroxidation
      indices, lipid quality and nutritional value, and antioxidants in growing pigs. 

PMID- 26207184
TI  - Conducting polymer electrodes for auditory brainstem implants.
AB  - The auditory brainstem implant (ABI) restores hearing in patients with damaged
      auditory nerves. One of the main ideas to improve the efficacy of ABIs is to
      increase spatial specificity of stimulation, in order to minimize extra-auditory
      side-effects and to maximize the tonotopy of stimulation. This study reports on
      the development of a microfabricated conformable electrode array with small (100
      MUm diameter) electrode sites. The latter are coated with a conducting polymer,
      PEDOT:PSS, to offer high charge injection properties and to safely stimulate the
      auditory system with small stimulation sites. We report on the design and
      fabrication of the polymer implant, and characterize the coatings in
      physiological conditions in vitro and under mechanical deformation. We
      characterize the coating electrochemically and during bending tests. We present a
      proof of principle experiment where the auditory system is efficiently activated
      by the flexible polymeric interface in a rat model. These results demonstrate the
      potential of using conducting polymer coatings on small electrode sites for
      electrochemically safe and efficient stimulation of the central auditory system.

PMID- 26207186
TI  - Persistent hyperglycemia modulates gut immune function and microbiota in rats.
AB  - BACKGROUND: Since hyperglycemia-induced cellular dysfunction could be associated
      with alterations of the immune system, we tested the hypothesis that
      hyperglycemia augments the aberrant immune responses such as inflammation and
      differentiation of CD4(+) T lymphocytes in the mesenteric lymph nodes (MLNs), and
      induces alterations of microbiota both under physiological and pathological
      conditions. METHODS: Male Wistar rats were randomly allocated into 4 groups:
      Control and Endotoxemia (lipopolysaccharide, LPS 1 mg/kg) with or without
      hyperglycemia. The hyperglycemia groups were administered glucose solution (10-40
      %), while the normoglycemia groups were administered saline. Alterations of the
      mRNA expressions of inflammatory cytokines and CD4(+) T lymphocyte
      transcriptional factor expressions in the MLNs, and those of the intestinal
      microbiota were analyzed at 24 hr. RESULTS: Hyperglycemia was kept approximately
      250-350 mg/dL during the 24 hr study period. At the end of 24 hr, hyperglycemia
      augmented the mRNA expressions of interleukin (IL)-1beta and IL-6 in the MLNs,
      while both the helper T (Th) 2 and regulatory-T (Treg) transcriptional factors
      were simultaneously up-regulated under non-endotoxemic condition. LPS injection
      significantly modulated the obligate anaerobe bacterial populations of the
      Bacteroidetes class, and altered the population sizes of the Clostridium
      perfringens and the Bacteroides fragilis subgroup. Hyperglycemia did not enhance
      these alterations of the microbiota evoked by LPS, although it did modify the
      bacterial populations of the L. reuteri subgroup and staphylococci in healthy
      condition without endotoxemia. CONCLUSIONS: The present study indicates that both
      gut immune function and microbiota are significantly modulated by persistent
      hyperglycemia.

PMID- 26207185
TI  - Catalytic Properties and Biomedical Applications of Cerium Oxide Nanoparticles.
AB  - Cerium oxide nanoparticles (Nanoceria) have shown promise as catalytic
      antioxidants in the test tube, cell culture models and animal models of disease.
      However given the reactivity that is well established at the surface of these
      nanoparticles, the biological utilization of Nanoceria as a therapeutic still
      poses many challenges. Moreover the form that these particles take in a
      biological environment, such as the changes that can occur due to a protein
      corona, are not well established. This review aims to summarize the existing
      literature on biological use of Nanoceria, and to raise questions about what
      further study is needed to apply this interesting catalytic material to
      biomedical applications. These questions include: 1) How does preparation,
      exposure dose, route and experimental model influence the reported effects of
      Nanoceria in animal studies? 2) What are the considerations to develop Nanoceria
      as a therapeutic agent in regards to these parameters? 3) What biological targets
      of reactive oxygen species (ROS) and reactive nitrogen species (RNS) are relevant
      to this targeting, and how do these properties also influence the safety of these
      nanomaterials?

PMID- 26207187
TI  - Identification of the Transmembrane Glucose Regulated Protein 78 as a Biomarker
      for the Brain Cancer Glioblastoma Multiforme by Gene Expression and Proteomic
      Studies.
AB  - The prognosis of patients with Glioblastoma Multiforme (GBM), the most malignant
      adult glial brain tumor, remains poor in spite of advances in treatment
      procedures, including surgical resection, irradiation and chemotherapy. Genetic
      heterogeneity of GBM warrants extensive studies to gain a thorough understanding
      of the biology of this tumor. While there have been several studies of global
      transcript profiling of glioma with the identification of gene signatures for
      diagnosis and disease management, translation into clinics is yet to happen. In
      the present study, we report a novel proteomic approach by using two-dimensional
      difference gel electrophoresis (2D-DIGE) followed by spot picking and analysis of
      proteins/peptides by Mass Spectrometry. We report Glucose Regulated Protein 78
      (GRP78) as a differentially expressed protein in the GBM cell line compared to
      human normal Astrocyte cells. In addition to proteomic studies, we performed
      microarray analysis which further confirmed up regulation of GRP78 in GBM cells
      compared to human normal Astrocyte cells. GRP78 has long been recognized as a
      molecular chaperone in the endoplasmic reticulum (ER) and can be induced by the
      ER stress response. Besides its location in the ER, GRP78 has been found in cell
      plasma membrane, cytoplasm, mitochondria, nucleus and other cellular secretions.
      GRP78 is implicated in tumor cell proliferation, apoptosis resistance, immune
      escape, metastasis and angiogenesis, and its elevated expression usually
      correlates with a variety of tumor micro environmental stresses, including
      hypoxia, glucose deprivation, lactic acidosis and inflammatory response. GRP78
      protein acts as a centrally located sensor of stress, which senses and
      facilitates the adaptation to the tumor microenvironment. Our findings showed
      differential expression of this gene in brain cancer GBM and thus confirm
      similarities in findings in existing transcriptional and translational studies.
      Thus, these findings could be of further importance for diagnostic, therapeutic
      and prognostic approaches for dealing with this highly malignant cancer.

PMID- 26207188
TI  - Characterization of Decellularized Heart Matrices as Biomaterials for Regular and
      Whole Organ Tissue Engineering and Initial In-vitro Recellularization with Ips
      Cells.
AB  - Tissue engineering strategies, based on solid/porous scaffolds, suffer from
      several limitations, such as ineffective vascularization, poor cell distribution
      and organization within scaffold, in addition to low final cell density, among
      others. Therefore, the search for other tissue engineering approaches constitutes
      an active area of investigation. Decellularized matrices (DM) present major
      advantages compared to solid scaffolds, such as ideal chemical composition, the
      preservation of vascularization structure and perfect three-dimensional
      structure. In the present study, we aimed to characterize and investigate murine
      heart decellularized matrices as biomaterials for regular and whole organ tissue
      engineering. Heart decellularized matrices were characterized according to: 1.
      DNA content, through DNA quantificationo and PCR of isolated genomic DNA; 2.
      Histological structure, assessed after Hematoxylin and Eosin, as well as Masson's
      Trichrome stainings; 3. Surface nanostructure analysis, performed, using SEM.
      Those essays allowed us to conclude that DM was indeed decellularized, with
      preserved extracellular matrix structure. Following characterization,
      decellularized heart slices were seeded with induced Pluripotent Stem cells
      (iPS). As expected, but - to the best of our knowledge - never shown before,
      decellularization of murine heart matrices maintained matrix biocompatibility, as
      iPS cells rapidly attached to the surface of the material and proliferated.
      Strikingly though, heart DM presented a differentiation induction effect over
      those cells, which lost their pluripotency markers after 7 days of culture in the
      DM. Such loss of differentiation markers was observed, even though bFGF
      containing media mTSR was used during such period. Gene expression of iPS cells
      cultured on DM will be further analyzed, in order to assess the effects of
      culturing pluripotent stem cells in decellularized heart matrices.

PMID- 26207189
TI  - Neurodevelopmental problems and extremes in BMI.
AB  - Background. Over the last few decades, an increasing number of studies have
      suggested a connection between neurodevelopmental problems (NDPs) and body mass
      index (BMI). Attention deficit/hyperactivity disorder (ADHD) and autism spectrum
      disorders (ASD) both seem to carry an increased risk for developing extreme BMI.
      However, the results are inconsistent, and there have been only a few studies of
      the general population of children. Aims. We had three aims with the present
      study: (1) to define the prevalence of extreme (low or high) BMI in the group of
      children with ADHD and/or ASDs compared to the group of children without these
      NDPs; (2) to analyze whether extreme BMI is associated with the subdomains within
      the diagnostic categories of ADHD or ASD; and (3) to investigate the contribution
      of genetic and environmental factors to BMI in boys and girls at ages 9 and 12.
      Method. Parents of 9- or 12-year-old twins (n = 12,496) were interviewed using
      the Autism-Tics, ADHD and other Comorbidities (A-TAC) inventory as part of the
      Child and Adolescent Twin Study in Sweden (CATSS). Univariate and multivariate
      generalized estimated equation models were used to analyze associations between
      extremes in BMI and NDPs. Results. ADHD screen-positive cases followed BMI
      distributions similar to those of children without ADHD or ASD. Significant
      association was found between ADHD and BMI only among 12-year-old girls, where
      the inattention subdomain of ADHD was significantly associated with the high
      extreme BMI. ASD scores were associated with both the low and the high extremes
      of BMI. Compared to children without ADHD or ASD, the prevalence of ASD screen
      positive cases was three times greater in the high extreme BMI group and double
      as much in the low extreme BMI group. Stereotyped and repetitive behaviors were
      significantly associated with high extreme BMIs. Conclusion. Children with ASD,
      with or without coexisting ADHD, are more prone to have low or high extreme BMIs
      than children without ADHD or ASD. 

PMID- 26207190
TI  - Integrating structure-from-motion photogrammetry with geospatial software as a
      novel technique for quantifying 3D ecological characteristics of coral reefs.
AB  - The structural complexity of coral reefs plays a major role in the biodiversity,
      productivity, and overall functionality of reef ecosystems. Conventional metrics
      with 2-dimensional properties are inadequate for characterization of reef
      structural complexity. A 3-dimensional (3D) approach can better quantify
      topography, rugosity and other structural characteristics that play an important
      role in the ecology of coral reef communities. Structure-from-Motion (SfM) is an
      emerging low-cost photogrammetric method for high-resolution 3D topographic
      reconstruction. This study utilized SfM 3D reconstruction software tools to
      create textured mesh models of a reef at French Frigate Shoals, an atoll in the
      Northwestern Hawaiian Islands. The reconstructed orthophoto and digital elevation
      model were then integrated with geospatial software in order to quantify metrics
      pertaining to 3D complexity. The resulting data provided high-resolution physical
      properties of coral colonies that were then combined with live cover to
      accurately characterize the reef as a living structure. The 3D reconstruction of
      reef structure and complexity can be integrated with other physiological and
      ecological parameters in future research to develop reliable ecosystem models and
      improve capacity to monitor changes in the health and function of coral reef
      ecosystems. 

PMID- 26207191
TI  - Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox.
AB  - Aim. In recent years, connectivity studies using neuroimaging data have increased
      the understanding of the organization of large-scale structural and functional
      brain networks. However, data analysis is time consuming as rigorous procedures
      must be assured, from structuring data and pre-processing to modality specific
      data procedures. Until now, no single toolbox was able to perform such
      investigations on truly multimodal image data from beginning to end, including
      the combination of different connectivity analyses. Thus, we have developed the
      Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox with the goal of
      diminishing time waste in data processing and to allow an innovative and
      comprehensive approach to brain connectivity. Materials and Methods. The MIBCA
      toolbox is a fully automated all-in-one connectivity toolbox that offers pre
      processing, connectivity and graph theoretical analyses of multimodal image data
      such as diffusion-weighted imaging, functional magnetic resonance imaging (fMRI)
      and positron emission tomography (PET). It was developed in MATLAB environment
      and pipelines well-known neuroimaging softwares such as Freesurfer, SPM, FSL, and
      Diffusion Toolkit. It further implements routines for the construction of
      structural, functional and effective or combined connectivity matrices, as well
      as, routines for the extraction and calculation of imaging and graph-theory
      metrics, the latter using also functions from the Brain Connectivity Toolbox.
      Finally, the toolbox performs group statistical analysis and enables data
      visualization in the form of matrices, 3D brain graphs and connectograms. In this
      paper the MIBCA toolbox is presented by illustrating its capabilities using
      multimodal image data from a group of 35 healthy subjects (19-73 years old) with
      volumetric T1-weighted, diffusion tensor imaging, and resting state fMRI data,
      and 10 subjets with 18F-Altanserin PET data also. Results. It was observed both a
      high inter-hemispheric symmetry and an intra-hemispheric modularity associated
      with structural data, whilst functional data presented lower inter-hemispheric
      symmetry and a high inter-hemispheric modularity. Furthermore, when testing for
      differences between two subgroups (<40 and >40 years old adults) we observed a
      significant reduction in the volume and thickness, and an increase in the mean
      diffusivity of most of the subcortical/cortical regions. Conclusion. While
      bridging the gap between the high numbers of packages and tools widely available
      for the neuroimaging community in one toolbox, MIBCA also offers different
      possibilities for combining, analysing and visualising data in novel ways,
      enabling a better understanding of the human brain. 

PMID- 26207193
TI  - Two new species of fossil Leggadina (Rodentia: Muridae) from Northwestern
      Queensland.
AB  - Only three species of fossil murine have been described to date in Australia even
      though they are often found in fossil deposits and can be highly useful in
      understanding environmental change over time. Until now the genus Leggadina, a
      group of short-tailed mice that is particularly well adapted to an arid
      environment, was only known from two extant species: L. forresti and L.
      lakedownensis. Here two new fossil species of the genus are described from sites
      in northwestern Queensland. Leggadina gregoriensis sp. nov. comes from the Early
      Pleistocene Rackham's Roost Site in the Riversleigh World Heritage Area and
      Leggadina macrodonta sp. nov. is from the Plio-Pleistocene Site 5C at Floraville
      Station. The evolution of the genus Leggadina and the lineage's response to
      palaeoecological factors is considered. Taphonomy of the two fossil deposits is
      examined and shows marked differences in both faunal composition of the
      assemblages and preservation. Description of L. gregoriensis and L. macrodonta
      extends the known temporal range of the Leggadina lineage by over 2 million
      years. 

PMID- 26207192
TI  - Rearing the scuttle fly Megaselia scalaris (Diptera: Phoridae) on industrial
      compounds: implications on size and lifespan.
AB  - Megaselia scalaris (Loew, 1866) (Diptera, phoridae) is a cosmopolitan fly species
      used in forensic science, and has been developed as a laboratory model species.
      They feed on decaying corpses as well as a wide variety of organic matter, and
      previous studies have even found them feeding on liquid paint or shoe polish,
      suggesting the possibility that they could breakdown industrial compounds. To
      test this possibility, we fed M. scalaris on a variety of industrially obtained
      materials and found that it was unable to complete its life cycle, dying at the
      larval stage, with the majority of compounds tested. However, when fed on
      modeling clay, a substrate that contains starch and inedible compounds, it was
      able to complete its life cycle. On this diet we observed increased larval
      development time, decreased pupal development time and a shortened adult life
      span. Additionally, pupae and adult flies were smaller than control flies.
      Contrary to previous reports, we find no evidence that M. scalaris is able to
      survive on modern formulations of liquid paint. 

PMID- 26207194
TI  - Coping with shorter days: do phenology shifts constrain aphid fitness?
AB  - Climate change can alter the phenology of organisms. It may thus lead seasonal
      organisms to face different day lengths than in the past, and the fitness
      consequences of these changes are as yet unclear. To study such effects, we used
      the pea aphid Acyrthosiphon pisum as a model organism, as it has obligately
      asexual clones which can be used to study day length effects without eliciting a
      seasonal response. We recorded life-history traits under short and long days,
      both with two realistic temperature cycles with means differing by 2  degrees C.
      In addition, we measured the population growth of aphids on their host plant
      Pisum sativum. We show that short days reduce fecundity and the length of the
      reproductive period of aphids. Nevertheless, this does not translate into
      differences at the population level because the observed fitness costs only
      become apparent late in the individual's life. As expected, warm temperature
      shortens the development time by 0.7 days/ degrees C, leading to faster
      generation times. We found no interaction of temperature and day length. We
      conclude that day length changes cause only relatively mild costs, which may not
      decelerate the increase in pest status due to climate change. 

PMID- 26207195
TI  - 70-kDa heat shock cognate protein expression as a putative biomarker of heavy
      metal burden in Mytilus galloprovincialis.
AB  - BACKGROUND: Heavy metals naturally occur in the marine environment and
      ecosystems. Due to anthropogenic influence they became common waters and coastal
      regions pollutants in particular where their concentrations remain hazardously
      high. We therefore tested a protocol for combined analysis of 6 heavy metal (Pb,
      Cd, Cr, Zn, Fe and Hg) concentrations in mussels Mytilus galloprovincialis
      collected from a coastal industrial zone (shipyard locality) and mariculture
      facilities in combination with expression analysis of multi xenobiotic resistance
      related genes and stress-related gene (HSC-70). FINDINGS: In this paper we tested
      a protocol for heavy-metal levels assessment by use of a highly sensitive
      analytical method, ICP-OES, combined with expression analysis of multi xenobiotic
      resistance related genes, including the stress-related gene encoding 70-kDa heat
      shock cognate protein on mussels (Mytillus Galloprovincialis). Mussels from the
      shipyard locality had higher heavy metal concentrations, except Fe. Higher metal
      concentrations did not influence expression of multi xenobiotic resistance
      related genes with exception of stress-related gene (HSC-70) encoding 70-kDa heat
      shock cognate protein. CONCLUSIONS: Our results indicate that mussels sampled in
      the industrial area have increased metal concentrations in comparison with the
      aquaculture locality, that are accompanied by increased transcript levels of HSC
      70.

PMID- 26207196
TI  - Decreased hormonal sensitivity after childbirth rather than the tumor size
      influences the prognosis of very young breast cancer patients.
AB  - PURPOSE: There is a significant difference in the mean tumor size between very
      young breast cancer patients and their elder counterparts. A simple comparison
      may show obvious prognostic differences. We investigated the prognostic impact of
      age by reducing the influence of the tumor size, which is thought to be a
      confounding factor. PATIENTS AND METHODS: We investigated 1,880 consecutive pT1
      4N0-3M0 breast cancer patients treated at less than 45 years of age between 1986
      and 2002 and conducted a case-control study of breast cancer subjects less than
      30 years of age. Each patient (Younger than 30) was matched with a corresponding
      control subject (Elder counterpart) based on an age 15 years above the patient's
      age, a similar tumor size and a status of being within 1 year after surgery. In
      addition, we assessed 47 patients with pregnancy-associated breast cancer (PABC).
      The levels of hormone receptors were measured using an enzyme immunoassay (EIA),
      and receptor-positive cases were divided into "weakly" and "strongly" positive
      groups based on the median value. Years from the last childbirth (YFLC) was
      categorized as "recent" and "past" at the time point of 8 years. RESULTS: There
      were fewer past YFLC cases, more partial mastectomy cases, a higher rate of
      scirrhous carcinoma or solid-tubular carcinoma in the Younger than 30 group than
      in the Elder counterpart group. The rates of a PgR-negative status in the Younger
      than 30 and Elder counterpart groups were 45.1 and 29.9%, respectively, As for
      the relationship between the PgR-negative rate and YFLC, the rates of a PgR
      negative status in the past YFLC, nulliparous, recent YFLC and PABC groups were
      31.9, 37.7, 44.4 and 65.7%, respectively. On the other hand, the rates of
      strongly positive cases were 42.6, 30.2, 22.2 and 8.6%, respectively. The 10-year
      recurrence-free survival rates in the Younger than 30, Elder counterpart and PABC
      groups were 61.7, 65.6 and 54.1%, respectively. The differences between the
      groups were not significant. In a multivariate analysis, independent prognostic
      facers included the number of lymph node metastases (4-9, HR:3.388, 95% CI 1.363
      8.425, p = 0.0086, over 10, HR: 6.714, 2.033-22.177, p = 0.0018), solid-tubular
      carcinoma (HR 3.348, 1.352-8.292, p = 0.0090), scirrhous carcinoma (HR 2.294,
      1.013-5.197, p = 0.0465) and past YFLC (HR 0.422, 0.186-0.956, p = 0.0387). An
      age younger than 30 was not found to be an independent prognostic factor.
      CONCLUSIONS: The prognosis of the very young women was the same as their elder
      counterparts with a matched tumor size, and age was not identified to be an
      independent prognostic factor according to the multivariate analysis. Recent
      childbirth probably influences the prognosis of patients younger than 30 years of
      age with breast cancer by lowering hormonal sensitivity.

PMID- 26207197
TI  - Chronic ileocolic intussusception due to transmural infiltration of diffuse large
      B cell lymphoma in a 14-year-old boy: a case report.
AB  - Chronic intussusception, defined as intussusception continuing over 14 days, is
      rare in children. We herein report a case of chronic ileocolic intussusception
      caused by the transmural infiltration of diffuse large B cell lymphoma in a 14
      year-old boy. The patient had been suffering from anorexia and intermittent
      abdominal pain for 5 weeks, during which his body weight decreased by around 7
      kg. Upon admission to our hospital, ultrasonography and enhanced computed
      tomography (CT) of the abdomen showed ileocolic intussusception. A retrospective
      examination of abdominal CT led us to suspect that the intussusception had
      initially appeared 5 weeks before admission, presumably coinciding with the
      beginning of the patient's abdominal symptoms. Since hydrostatic reduction was
      unsuccessful, laparotomy was performed, which showed unreducible ileocolic
      intussusception with a marked edematous ileum and mesentery. Ileocecal resection
      without lymph node dissection was carried out, and a histological examination of
      the resected specimen revealed the transmural infiltration of diffuse large B
      cell lymphoma of the terminal ileum. The patient's postoperative course was
      uneventful, and adjuvant chemotherapy was administered. This case illustrates the
      diagnostic challenges of confirming 'chronic' intussusception in older children. 

PMID- 26207198
TI  - Phytotoxicity of Alachlor, Bromacil and Diuron as single or mixed herbicides
      applied to wheat, melon, and molokhia.
AB  - This study investigated the phytotoxicity of herbicides applied singly or as
      mixtures to different crops under greenhouse conditions. Growth inhibition of the
      crops was taken as an indicator of phytotoxicity. Phytotoxicity of mixtures was
      estimated by calculating EC50 value in toxic units. EC50 (mg/kg soil) of
      Alachlor, Bromacil and/or Diuron were: 11.37, 4.77, 1.64, respectively, on melon;
      0.11, 0.08, 0.24, respectively, on molokhia, and 3.91, 3.08, 1.83, respectively,
      on wheat. EC50 values of binary mixture tests of (Alachlor + Bromacil), (Alachlor
      + Diuron), and (Bromacil + Diuron) were 12.21, 5.84, 10.22 on melon, 0.982,
      925.4, 38.1 on molokhia, and 0.673, 1.34, 0.644 on wheat. Tertiary mixture tests
      showed EC50 values (TU/kg soil) of (Alachlor + Bromacil + Diuron) was 633.9 on
      melon, 3.02 on molokhia and 32.174 on wheat. Diuron was more toxic than Alachlor
      and Bromacil to the tested crops based on individual tests. Molokhia was the most
      sensitive crop to herbicides. Binary mixtures showed a synergistic effect as
      compared to the tertiary mixtures. 

PMID- 26207199
TI  - d-Neighborhood system and generalized F-contraction in dislocated metric space.
AB  - This paper, gives an answer for the Question 1.1 posed by Hitzler (Generalized
      metrics and topology in logic programming semantics, 2001) by means of
      "Topological aspects of d-metric space with d-neighborhood system". We have
      investigated the topological aspects of a d-neighborhood system obtained from
      dislocated metric space (simply d-metric space) which has got useful applications
      in the semantic analysis of logic programming. Further more we have generalized
      the notion of F-contraction in the view of d-metric spaces and investigated the
      uniqueness of fixed point and coincidence point of such mappings. 

PMID- 26207200
TI  - Phosphine-Initiated General-Base-Catalyzed Quinolone Synthesis.
AB  - Phosphinocatalysis provides a new approach toward 3-substituted-4-quinolones. A
      simple procedure, which uses Ph3P as an inexpensive catalyst and S-phenyl 2-(N
      tosylamido)benzothioates and activated alkynes as starting materials, provides
      direct access to several 3-aroyl-4-quinolones and methyl 4-quinolone-3
      carboxylate esters. The reaction presumably occurs through general base
      catalysis, with the initial addition of Ph3P to the activated alkyne generating
      the phosphonium enoate zwitterion, which acts as the strong base that initiates
      the reaction.

PMID- 26207201
TI  - One-Carbon Metabolism and Colorectal Cancer: Potential Mechanisms of
      Chemoprevention.
AB  - For many years folic acid has been evaluated for its utility as a chemopreventive
      agent due to its position at the center of the one-carbon metabolic network. This
      network is responsible for generating precursors to nucleotide synthesis as well
      as the one-carbon moieties used in DNA methylation reactions, two mechanisms
      which are frequently disrupted during carcinogenesis. While the use of folic acid
      for the chemoprevention of colorectal cancer is still controversial, there is
      evidence that folic acid intake has significant influence on these fundamental
      cellular mechanisms. Folic acid has a dual role with regards to nucleotide
      synthesis and colorectal cancer (CRC) prevention; in a healthy colon, adequate
      folate status is important for nucleotide metabolism homeostasis and the
      maintenance of DNA integrity, however in a colon harboring premalignant lesions
      lowered folate status may help to eliminate transformed cells. In addition, folic
      acid is important for the generation of the one-carbon groups used in DNA
      methylation reactions, and modulation of folic acid metabolism may be useful in
      combating the aberrant DNA methylation during carcinogenesis. Interestingly, it
      has been revealed that decreased folic acid intake can dampen the inflammatory
      response, which has recently been a popular strategy for colorectal cancer
      chemoprevention. In this review we discuss the molecular mechanisms influenced by
      folic acid intake and how they might be relevant to cancer chemoprevention in
      greater detail.

PMID- 26207202
TI  - Sociospatial patterning of the use of new transport infrastructure: Walking,
      cycling and bus travel on the Cambridgeshire guided busway.
AB  - BACKGROUND: New transport infrastructure may help promote active travel, thereby
      contributing to increasing overall physical activity and population health gain.
      In 2011 a guided busway with a path for walking and cycling was opened in
      Cambridgeshire, UK. This paper investigates the predictors of walking, cycling
      and bus use on the busway. METHODS: Cross-sectional analyses of the final
      questionnaire wave (2012) of the Commuting and Health in Cambridge cohort study
      following the opening of the busway. Participants were 453 adult commuters who
      had not moved home or workplace. Busway use was self-reported and proximity
      calculated using GIS. Separate multivariable logistic regression models were used
      to assess predictors of walking, cycling and bus use on the busway. RESULTS:
      Exposure to the intervention (proximity: the negative square root of the distance
      from home to busway in kilometres) increased the odds of use for cycling (OR
      2.18; 95% CI 1.58 to 3.00), bus travel (OR 1.53, 95% CI 1.15 to 2.02) and walking
      (OR 1.34; 95% CI 1.05 to 1.70). The effect of exposure was strengthened in towns
      for bus use, and in towns and villages for walking, compared with urban areas.
      Men were more likely than women to have cycled on the busway, whereas individual
      socioeconomic characteristics did not predict bus use or walking. CONCLUSION: New
      high-quality transport infrastructure attracts users, determined by geographical
      exposure and spatial contextual factors such as settlement size and availability
      of parking at work. Future longitudinal analyses will determine effects on
      overall travel and physical activity behaviour change.

PMID- 26207204
TI  - Is chest radiation now a classical practice for extensive small cell lung cancer?
AB  - The recent phase III published by Slotman et al. addressed the question of
      additional chest radiation showing a benefit mainly in local control. A critical
      analysis of this trial point out all the limitations and in view of other
      studies, the real benefit of chest radiation for extensive small cell lung cancer
      (SCLC) remains unclear. 

PMID- 26207206
TI  - First-line nivolumab (anti-PD-1) monotherapy in advanced NSCLC: the story of
      immune checkpoint inhibitors and "the sorcerers apprentice".

PMID- 26207205
TI  - Consolidative radiation therapy for extensive-stage small cell lung cancer.
AB  - Despite the use of systemic therapy and prophylactic cranial irradiation (PCI),
      outcomes for patients with extensive-stage small cell lung cancer (ES-SCLC)
      remain poor. Consolidative radiation therapy (RT) to the chest may improve
      outcomes by improving local control. In a recently completed multi-institutional
      phase III clinical trial, investigators randomized patients with ES-SCLC and
      response to chemotherapy to PCI with or without consolidative RT. Two-year
      overall survival (OS) and 6-month progression-free survival (PFS) were improved
      with the use of consolidative RT; however, the prognosis for ES-SCLC in the
      experimental arm was still poor and there was no statistically significantly
      difference in 1-year OS, the trial's primary endpoint. In this editorial, the
      results of this trial are discussed and the methods are compared to those used in
      other trials of consolidative RT in ES-SCLC. More research is needed to identify
      the optimal RT dose and fractionation and to clarify the role of consolidative RT
      in ES-SCLC. 

PMID- 26207203
TI  - Meeting Report: New Directions in the Biology and Disease of Skeletal Muscle
      2014.
AB  - The New Directions in the Biology and Disease of Skeletal Muscle is a scientific
      meeting, held every other year, with the stated purpose of bringing together
      scientists, clinicians, industry representatives and patient advocacy groups to
      disseminate new discovery useful for treatment inherited forms of neuromuscular
      disease, primarily the muscular dystrophies. This meeting originated as a
      response the Muscular Dystrophy Care Act in order to provide a venue for the free
      exchange of information, with the emphasis on unpublished or newly published
      data. Highlights of this years' meeting included results from early phase
      clinical trials for Duchenne Muscular Dystrophy, progress in understanding the
      epigenetic defects in Fascioscapulohumeral Muscular Dystrophy and new mechanisms
      of muscle membrane repair. The following is a brief report of the highlights from
      the conference.

PMID- 26207207
TI  - Erlotinib alone or with bevacizumab as first-line therapy in patients with
      advanced non-squamous non-small-cell lung cancer harboring EGFR mutations
      (JO25567): an open-label, randomized, multicenter, phase II study.

PMID- 26207208
TI  - Anatomic segmentectomy for non-small cell lung cancer: can we believe the hype?

PMID- 26207209
TI  - Improved overall survival following tyrosine kinase inhibitor treatment in
      advanced or metastatic non-small-cell lung cancer-the Holy Grail in cancer
      treatment?
AB  - Advanced or metastatic non-small-cell lung cancer (NSCLC) is characterized by a
      poor prognosis and few second- or third-line treatments. First-generation
      epidermal growth factor receptor tyrosine kinase inhibition has paved the way for
      targeted therapies in lung cancer. Although these drugs result in excellent
      responses [and significantly improved progression-free survival (PFS)] in
      patients with activating EGFR mutations, none of these randomized studies has yet
      demonstrated a statistically significant improvement of overall survival (OS).
      PFS is often used as a predictor for improved OS since it is independent of
      subsequent treatment, but OS is acknowledged as the key clinical outcome in the
      treatment of advanced NSCLC. When effective treatment is given as post therapy,
      it will be difficult to distinguish the treatment effect of original and
      subsequent treatments because differences in OS are potentially confounded by
      crossover, and a relevant number of patients assigned to chemotherapy arms
      received tyrosine kinase inhibitors (TKIs) as second- or third-line treatment
      after disease progression. The high proportion of crossover may extend the
      benefit associated with the administration of TKIs to patients assigned to the
      control arm, and its "salvage"-effect may compensate for the relevant differences
      in PFS of first-line treatment consistently demonstrated in all TKI trials.
      Results for the INFORM trial (maintenance therapy with gefitinib following
      platinum-based chemotherapy) provided evidence that maintenance therapy with
      gefitinib significantly improved PFS, with greatest benefit in patients harboring
      EGFR mutation. Despite a high crossover rate (53%) final OS results of this study
      have now demonstrated a significant survival benefit for the gefitinib-treated
      EGFR mutation-positive patients (46.9 vs. 21.0 months, P=0.036). This is the
      first randomized clinical trial that showed a significant and clinical meaningful
      OS benefit in EGFR mutation-positive NSCLC patients following maintenance therapy
      with gefitinib as compared to placebo. It remains to be seen whether further
      exploration of this treatment strategy will confirm these promising results. 

PMID- 26207210
TI  - (18)F-FDG-PET/CT in the assessment of pulmonary solitary nodules: comparison of
      different analysis methods and risk variables in the prediction of malignancy.
AB  - OBJECTIVE: To compare the diagnostic performance of different metabolical,
      morphological and clinical criteria for correct presurgical classification of the
      solitary pulmonary nodule (SPN). METHODS: Fifty-five patients, with SPN were
      retrospectively analyzed. All patients underwent preoperative (18)F
      fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography
      (CT). Maximum diameter in CT, maximum standard uptake value (SUVmax),
      histopathologic result, age, smoking history and gender were obtained. Different
      criteria were established to classify a SPN as malignant: (I) visually detectable
      metabolism, (II) SUVmax >2.5 regardless of SPN diameter, (III) SUVmax threshold
      depending of SPN diameter, and (IV) ratio SUVmax/diameter greater than 1. For
      each criterion, statistical diagnostic parameters were obtained. Receiver
      operating characteristic (ROC) analysis was performed to select the best
      diagnostic SUVmax and SUVmax/diameter cutoff. Additionally, a predictive model of
      malignancy of the SPN was derived by multivariate logistic regression. RESULTS:
      Fifteen SPN (27.3%) were benign and 40 (72.7%) malignant. The mean values +/-
      standard deviation (SD) of SPN diameter and SUVmax were 1.93+/-0.57 cm and 3.93+/
      2.67 respectively. Sensitivity (Se) and specificity (Sp) of the different
      diagnostic criteria were (I): 97.5% and 13.1%; (II) 67.5% and 53.3%; (III) 70%
      and 53.3%; and (IV) 85% and 33.3%, respectively. The SUVmax cut-off value with
      the best diagnostic performance was 1.95 (Se: 80%; Sp: 53.3%). The predictive
      model had a Se of 87.5% and Sp of 46.7%. The SUVmax was independent variables to
      predict malignancy. CONCLUSIONS: The assessment by semiquantitative methods did
      not improve the Se of visual analysis. The limited Sp was independent on the
      method used. However, the predictive model combining SUVmax and age was the best
      diagnostic approach.

PMID- 26207211
TI  - Prognostic value of Twist in lung cancer: systematic review and meta-analysis.
AB  - BACKGROUND: Twist is identified as an epithelial-mesenchymal transition (EMT)
      regulator which has been considered to induce metastasis. However, the prognostic
      value of Twist in patients with lung cancer remains controversial. METHODS: A
      search of database including EMBASE, Medline, ISI Web of knowledge and PubMed was
      performed. Eligible articles studying on the prognostic significance of Twist
      were included in this meta-analysis. Pooled hazard ratios (HRs) and their
      corresponding 95% confidence intervals (CIs) were assessed to quantify the
      prognostic role. RESULTS: A total of five studies were included. The pooled HR
      for Twist was 1.949 (95% CI: 1.408-2.698, I(2)=42.7%, P<0.001), suggesting high
      Twist expression is associated with poor prognosis in lung cancer patients. Our
      sensitivity analyses suggested the robustness of the results. Neither Begg's test
      nor Egger's test found publication bias in any analysis. CONCLUSIONS:
      Overexpressed Twist in lung cancer tissue indicated poor prognosis.

PMID- 26207212
TI  - Dysregulation of the Met pathway in non-small cell lung cancer: implications for
      drug targeting and resistance.
AB  - The receptor tyrosine kinase, Met, orchestrates a complex signalling network that
      physiologically drives a programme of 'invasive growth'. In cancer however, this
      process may be co-opted to promote proliferation, survival and metastasis of
      cancer cells. Met is thus a key therapeutic target, not least in non-small cell
      lung cancer (NSCLC) where it is one of the most commonly dysregulated driver
      oncogenes. Identifying robust biomarkers that allow the selection of patients
      most likely to respond to Met targeted therapies will however be essential to
      realising their potential. This has been underlined recently by the early
      termination of three pivotal phase III trials investigating Met targeted agents
      in NSCLC, all of which failed to show clinical benefit. In contrast to these
      trials, which were relatively unselective, a couple of early phase trials have
      recently been instigated that select patients on the basis of Met amplification.
      While still at an early stage, interim results are relatively encouraging and
      strengthen the rationale for using Met amplifaction as a biomarker. Here we will
      discuss this and other aberrations in Met signalling in relation to their
      significance in the therapeutic targeting of Met. 

PMID- 26207213
TI  - The past, present and future of immunotherapy against tumor.
AB  - Tumor is one of the most common lethal diseases in the world. Current progress of
      therapy remains insufficient survival benefit. Tumor immunotherapies have been
      proposed for more than a century. With the improvement in the understanding of
      the role of the immune system in the tumorigenesis and immune response to tumor,
      immunotherapy has obtained a rapid development and plays the significant role in
      tumor therapy nowadays. This review designs to provide a general overview of
      immunotherapy in tumors. We will introduce the landmark events in the past
      research of immunotherapy and elaborate a range of strategies using different
      immune response mechanism, which have been demonstrated successfully and even
      some of them have been approved by US Food and Drug Administration (FDA) to
      certain tumor therapy. Finally, we will discuss the future direction of
      immunotherapy so that we can predict the possible and valuable strategies for
      future tumor therapy. 

PMID- 26207214
TI  - The radiation techniques of tomotherapy & intensity-modulated radiation therapy
      applied to lung cancer.
AB  - Radiotherapy (RT) plays an important role in the management of lung cancer.
      Development of radiation techniques is a possible way to improve the effect of RT
      by reducing toxicities through better sparing the surrounding normal tissues.
      This article will review the application of two forms of intensity-modulated
      radiation therapy (IMRT), fixed-field IMRT and helical tomotherapy (HT) in lung
      cancer, including dosimetric and clinical studies. The advantages and potential
      disadvantages of these two techniques are also discussed. 

PMID- 26207215
TI  - Screening for lung cancer using low-dose computed tomography: concerns about the
      application in low-risk individuals.
AB  - Low-dose computed tomography (LDCT) has been increasingly accepted as an
      efficient screening method for high-risk individuals to reduce lung cancer
      mortality. However, there remains a gap of knowledge in the practical
      implementation of screening on a larger scale, especially for low-risk
      individuals. The aim of this study is to initiate discussion through an evidence
      based analysis and provide valuable suggestions on LDCT screening for lung cancer
      in clinical practice. Among previously published randomized controlled trials
      (RCTs), the National Lung Screening Trial (NLST) is the only one demonstrating
      positive results in a high-risk population of old age and heavy smokers. It is
      also shown that the potential harms include false-positive findings, radiation
      exposure etc., but its magnitude is uncertain. In the meantime, the current risk
      stratification system is inadequate, and is difficult to define selection
      criteria. Thus, the efficacy of LDCT in lung cancer screening needs to be
      confirmed in future trials, and the procedure should not be proposed to
      individuals without comparable risk to those in the NLST. Furthermore, there is a
      lack of evidence to support the expansion of LDCT screening to low-risk
      individuals. Therefore, recommendation of LDCT screening for these patients could
      be premature in clinical practice although some of them might be missed based on
      current definition of risk factors. Further studies and advances in risk
      assessment tools are urgently needed to address the concerns about lung cancer
      screening in order to improve the outcomes of lung cancer. 

PMID- 26207216
TI  - Chitinase-3-like-1/YKL-40 as marker of circulating tumor cells.
AB  - Ex vivo expansion of circulating tumor cells (CTCs) of small cell lung cancer
      (SCLC) patients enabled systematic screening of secreted cytokines. Permanent CTC
      cultures of different patients shared secretion of chitinase-3-like-1
      (CHI3L1)/YKL-40, known to be upregulated in a range of tumor entities and to be
      associated with increased metastasis and decreased survival. This protein lacks
      enzymatic activity and its mechanism of promoting tumor dissemination has not
      been resolved. Results from SCLC CTC cultures suggest CHI3L1 as marker and
      important effector of tumor cell dissemination in the peripheral blood.
      Furthermore, this protein may link chronic inflammation of the lung, chronic
      obstructive pulmonary disease (COPD) and lung cancer. 

PMID- 26207218
TI  - Professor Robert Pirker: primary prevention and early detection of lung cancer
      should be strengthened.

PMID- 26207217
TI  - Which patients with extensive stage small-cell lung cancer should and should not
      receive thoracic radiotherapy?

PMID- 26207219
TI  - Professor Helmut H. Popper: the major challenges and potential solutions for
      future management of lung cancer.

PMID- 26207220
TI  - Clinicopathologic characteristics of patients with ROS1 fusion gene in non-small
      cell lung cancer: a meta-analysis.
AB  - BACKGROUND: The receptor tyrosine kinase ROS1 is a driver gene in the non-small
      cell lung cancer (NSCLC) with promising target treatment potential. The clinical
      features of NSCLC patients harboring ROS1 fusion gene were not fully understood
      due to small-to-modest sample sizes of these association studies. METHODS: We
      systematically searched PubMed, EMBASE, and the Cochrane Central Register of
      Controlled Trials (CENTRAL) from their inception to March 31, 2015. We analyzed
      the association between ROS1 fusion genes and four common clinical variables,
      i.e., gender, smoking status, pathological type and clinical stage. RESULTS:
      Eighteen studies consisting of 9,898 NSCLC patients were included in this meta
      analysis. Pooled results showed that significantly higher rate of ROS1 fusion
      gene was detected in female NSCLC patients (OR =1.54, 95% CI: 1.02-2.34,
      P=0.042), patients without a smoking history (OR =3.27, 95% CI: 1.44-7.45,
      P=0.005), patients with adenocarcinomas NSCLC (OR =10.24, 95% CI: 5.13-20.40,
      P<0.001), and patients with an advanced clinical stages III-IV (OR =2.57, 95% CI:
      1.78-3.71, P<0.001). The pooled prevalence of ROS1 fusion gene was 2.4% (95% CI:
      1.8-3.1%) in adenocarcinoma and a significantly lower (0.2%) in non
      adenocarcinoma tumors. CONCLUSIONS: ROS1 rearrangement was more prevalent in
      female patients, patients without a smoking history, patients with
      adenocarcinoma, and patients on more advanced stages (stages III to IV).

PMID- 26207221
TI  - Expert consensus on image-guided radiofrequency ablation of pulmonary tumors-2015
      edition.

PMID- 26207222
TI  - Evaluation of fetal cell transplantation safety in treatment of diabetes: a three
      year follow-up.
AB  - BACKGROUND: Rapidly increasing prevalence of diabetes throughout the world
      highlights the importance of looking for new treatment options for the disease
      such as stem cell therapy. With regard to the increasing attention towards stem
      cell therapy as a curative treatment for diabetes in recent years, it is of
      crucial importance to ensure the safety of this novel therapeutic technique. In
      this study we aim to evaluate the safety of fetal liver-derived cell suspension
      allotransplantation in the diabetic patients who had attended a clinical trial in
      2007. METHODS: 44 out of a total number of 56 patients who had undergone either
      fetal liver-derived cell suspension allotransplantation or placebo injection in
      2007 (IRCT number: 138811071414 N10) were contacted and recruited for the
      evaluation of possible complications. Patients were referred to a designated
      ophthalmologist and cardiologist to be screened for retinopathy and
      cardiovascular diseases. 24-hour urine was collected and tested for the
      evaluation of nephropathy; and, neuropathy was assessed by means of neuropathic
      symptoms and monofilament test. RESULTS: There were no life-threatening
      complications nor significant differences in terms of evaluated diabetes
      complications ( retinopathy, neuropathy, nephropathy and cardiovascular diseases
      ) between the case and control groups. However, one case of meningioma was
      reported. CONCLUSIONS: Findings of our study demonstrated that stem cell
      transplantation can be considered a relatively safe procedure apart from one case
      of meningioma; it did neither cause any life-threatening complications nor
      increased the rate of the diabetes micro- and macrovascular complications.

PMID- 26207223
TI  - The multiple facets of alpha-1-antitrypsin.
AB  - Alpha-1-antitrypsin (AAT) is recognised as a potent inhibitor of serine
      proteinases. Genetic deficiency is associated with several neutrophilic diseases
      including severe emphysema. This is believed to reflect the loss of inhibition of
      neutrophilic serine proteinases that then result in local tissue damage (the
      proteinase/antiprotease hypothesis). In recent years the role of AAT in the
      control of inflammatory and immunological processes has become identified.
      Although in some instances this may reflect its ability to control pro
      inflammatory effects of serine proteinases it has also become recognised that it
      has non proteolytic mediated functions. This poly functional role is starting to
      become recognised offering a possibility of its use as a therapeutic agent in
      many clinical disease areas. The current review explores both the traditional and
      non-traditional function of AAT through published literature. 

PMID- 26207224
TI  - What can we learn from AOANJRR 2014 annual report?

PMID- 26207225
TI  - Bone marrow edema and results after cartilage repair.

PMID- 26207226
TI  - The epidemiology and health care burden of tennis elbow: a population-based
      study.

PMID- 26207227
TI  - Clinical translation of tissue-engineered constructs for severe leg injuries.

PMID- 26207228
TI  - Roscovitine in cancer and other diseases.
AB  - Roscovitine [CY-202, (R)-Roscovitine, Seliciclib] is a small molecule that
      inhibits cyclin-dependent kinases (CDKs) through direct competition at the ATP
      binding site. It is a broad-range purine inhibitor, which inhibits CDK1, CDK2,
      CDK5 and CDK7, but is a poor inhibitor for CDK4 and CDK6. Roscovitine is widely
      used as a biological tool in cell cycle, cancer, apoptosis and neurobiology
      studies. Moreover, it is currently evaluated as a potential drug to treat
      cancers, neurodegenerative diseases, inflammation, viral infections, polycystic
      kidney disease and glomerulonephritis. This review focuses on the use of
      roscovitine in the disease model as well as clinical model research. 

PMID- 26207230
TI  - Comparison of different stimulation protocols used in in vitro fertilization: a
      review.
AB  - Infertility is one of the major medical problems in the western world caused by
      genetic or epigenetic factors, or both, which has led to continuous research and
      advancements in the field of assisted reproductive technology (ART). Many
      stimulation protocols are available for controlled ovarian hyperstimulation (COH)
      in in vitro fertilization (IVF). This review compares the agonist long protocol,
      antagonist protocol and minimal stimulation protocol. Gonadotropin-releasing
      hormone (GnRH) antagonist and minimal stimulation protocol has shorter duration
      of treatment and less gonadotropin use. GnRH agonist long protocol is better in
      folliculogenesis and pregnancy rate, which is the imperative goal of COH. Despite
      its costly and lengthy approach, GnRH agonist long protocol has delivered
      satisfactory results in most women. On the other hand, patients with poor ovarian
      reserve may have greater advantage when considering minimal stimulation protocol.
      Evidently, it is crucial to have a larger scale studies with more focused
      comparisons, which take into account the differences in patients' response
      criteria and additional confounding variables (age, BMI, previous IVF outcomes
      etc.), in order to reach to a more definite conclusions. 

PMID- 26207229
TI  - Role of pro-inflammatory cytokines released from microglia in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the
      brain, which is characterized by the formation of extracellular amyloid plaques
      (or senile plaques) and intracellular neurofibrillary tangles. However,
      increasing evidences demonstrated that neuroinflammatory changes, including
      chronic microgliosis are key pathological components of AD. Microglia, the
      resident immune cells of the brain, is constantly survey the microenvironment
      under physiological conditions. In AD, deposition of beta-amyliod (Abeta) peptide
      initiates a spectrum of cerebral neuroinflammation mediated by activating
      microglia. Activated microglia may play a potentially detrimental role by
      eliciting the expression of pro-inflammatory cytokines such as interleukin (IL)
      1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) influencing the
      surrounding brain tissue. Emerging studies have demonstrated that up-regulation
      of pro-inflammatory cytokines play multiple roles in both neurodegeneration and
      neuroprotection. Understanding the pro-inflammatory cytokines signaling pathways
      involved in the regulation of AD is crucial to the development of strategies for
      therapy. This review will discuss the mechanisms and important role of pro
      inflammatory cytokines in the pathogenesis of AD, and the ongoing drug targeting
      pro-inflammatory cytokine for therapeutic modulation. 

PMID- 26207232
TI  - Digital tomosynthesis in lung cancer: state of the art.
AB  - Chest digital tomosynthesis (CDT) is a limited angle image tomography, which
      improves the visibility of anatomy compared with radiographic imaging. Due to the
      limited acquisition angle of CDT, it has the potential to significantly increase
      the temporal resolution of patient surveillance at the cost of reduced resolution
      in one direction. CDT is 3 times more effective in identifying pulmonary nodules
      compared to conventional radiography and at lower doses and cost compared with
      routine chest computed tomography (CT) examinations. There is only one report in
      which CDT was used in a single-arm observational study for lung cancer detection
      in at-risk population while a few studies suggested that CDT sensitivity is
      superior to radiography but inferior to CT in detecting lung nodules, other
      studies on the accuracy of CDT suggest that the specificity is much closer to CT
      than radiography. Therefore, large-scale randomized controlled trial would be
      needed to confirm benefits of CDT and identify where it is best used in the
      clinical setting. CDT seems to be a cost-effectiveness first-line lung cancer
      screening tool to detect potential lung cancer nodule. 

PMID- 26207233
TI  - Robotic thoracic surgery of the right posterior inferior mediastinal mass.

PMID- 26207231
TI  - Sinus thrombosis-do animal models really cover the clinical syndrome?
AB  - Cerebral venous sinus thrombosis (CVST) is an important cause of stroke in young
      patients. CVST represents with 0.5-3% of stroke cases a relatively rare disease.
      CVST affects 3-4 cases per 1 million overall and 7 cases per 1 million children
      and neonates. Typical clinical symptoms include headache, visual deficits and
      seizures. Beside the main condition associated with CVST in women in pregnancy
      and puerperium, the most frequently identified risk factors are oral hormonal
      contraceptives in combination with coagulation disorders. The initial treatment
      contains heparin and its efficacy is based on two randomized placebo-controlled
      trials including 79 patients together. A lack of understanding of the
      pathophysiology of CSVT makes animal models of this disease indispensable.
      Previously developed animal models of sinus sagittalis superior contributes to
      further clarify the pathophysiologic mechanisms and surrounding circumstances in
      the topic of cerebral venous thrombosis. 

PMID- 26207234
TI  - Robotic thoracic surgery of the left pleural cupula mediastinal mass.

PMID- 26207235
TI  - Update on basic and clinical aspects of osteoarthritis.

PMID- 26207236
TI  - Thoracic surgery: single-port video-assisted thoracoscopic lobectomy.
AB  - Single-port video-assisted thoracoscopic surgery (VATS) has been increasingly
      applied in clinical settings in the past two years along with the improvements in
      both endoscopic instruments and surgical skills. Our center began to perform
      single-port VATS lobectomy in May 2014 and had performed this procedure in 121
      patients till January 2015. The surgical incision (3.5-4.5 cm in length) was
      created in the 4(th) or 5(th) intercostal space at the anterior axillary line at
      the diseased side. The operator standed at the abdominal side of the patient and
      operated using the endoscopic instruments only. The surgical steps of single-port
      VATS lobectomy were same as those of the triple-port VATS lobectomy. There was no
      fixed mode in handling the three major structures of the pulmonary lobes, and the
      resection sequence can be scheduled based on the development status of pulmonary
      fissures and on the difficulties in dissecting the relevant structures. We
      believe the single-port VATS lobectomy is a safe and feasible procedure and
      warrants further clinical applications after finishing these surgeries. 

PMID- 26207237
TI  - Professor Takashi Suda: we should not compromise the safety and precision of a
      thoracic surgery.

PMID- 26207238
TI  - Somatostatin receptors over-expression in castration resistant prostate cancer
      detected by PET/CT: preliminary report of in six patients.
AB  - Prostate cancer (PC) is usually characterized by an excellent prognosis, largely
      due to little biological aggressiveness and the power of hormonal deprivation
      therapy. In spite of these favorable characteristics, however, a significant
      quota of patients does not respond to androgen deprivation therapy (ADT) and
      develop a progressive disease. Castration-resistant prostate cancer (CRPC) is
      defined by disease progression in spite of ADT. This progression may show any
      combination of a rise in serum prostate-specific antigen (PSA), clinical and
      radiological progression of pre-existing disease, and appearance of new
      metastases. This event is a striking change in the clinical scenario, since the
      power of treatment for CRPC patients with distant metastases is very limited.
      Somatostatin is a hormone produced by neuroendocrine cells. Its distant effects
      are mediated by the binding to five specific receptors, which are the most
      striking parameter for neuroendocrine. Various synthetic somatostatin agonists
      able to bind to the receptors have been synthesized during the past two decades
      for diagnostic and therapeutic purposes. Octreotide, the most popular of these,
      is widely used to treat patients affected by neuroendocrine tumors. A number of
      researches carried out in the past evaluated the possible neuroendocrine
      differentiation (NED) of PC cells in the castration resistant phase. If proved,
      the presence of a specific class of receptor on cell's surfaces should give a
      potentially biological target to be used for therapy. However, these studies led
      to contradictory results. Aim of our phase III diagnostic trial was to study "in
      vivo" the over-expression of somatostatin receptors (SSTRs) in CRPC patients by
      PET/CT after the administration of the somatostatin analog [(68)Ga-DOTANOC,1
      Nal(3)]-octreotide labeled with (68)Ga. Every area of increased uptake
      corresponding to a metastasis detected with other methods was considered as SSTRs
      expressing. False positivity to SSTRs expression was considered those
      localizations with a suspicious uptake not confirmed by other radiologic
      procedures. On the other hand, metastatic lesions lacking the
      radiopharmaceutical's uptake were considered not SSTRs expressing metastases. The
      preliminary results in 6 of the 67 patients scheduled by our phase III trial
      showed metastases with a variable SSTRs expression in 2 patients. 

PMID- 26207240
TI  - ATM is sponsored by the Affiliated Nanjing Jiangning Hospital of Nanjing Medical
      University.

PMID- 26207239
TI  - Author response: new therapies for reducing post-myocardial left ventricular
      remodeling.

PMID- 26207241
TI  - Stereotactic ablative radiotherapy and surgery: two gold standards for early
      stage non-small cell lung cancer?
AB  - There is growing clinical equipoise between surgery and stereotactic ablative
      radiotherapy (SABR) in the management of early-stage non-small cell lung cancer
      (ES-NSCLC). Increasing evidence suggest similar outcomes between these
      modalities. Through the guidance of a multidisciplinary team, a shared decision
      making approach in this setting in favoured. 

PMID- 26207243
TI  - The anti-CD40 auto-antibody: a biomarker or a factor for the permeability of
      recurrent focal segmental glomerulosclerosis?

PMID- 26207242
TI  - "Old people suffer the ravages of the years": changes of treatments in elderly
      patients with early stage non-small cell lung cancer.
AB  - The increase in life expectancy and the spreading of lung cancer screening led to
      a further rise of newly detected non-small cell lung cancer (NSCLC) cases. Age,
      per se, should not be considered a contraindication for treatments in fit
      patients. Early stage NSCLC is more and more treated with minimally invasive
      surgery. Stereotactic ablative radiation therapy (SABR) has been developed as an
      innovative therapy for stage I NSCLC and is now considered a standard treatment
      option for medically inoperable patients or for patient who refuse operation.
      Preoperative careful functional evaluations either respiratory or cardiovascular,
      as well as preoperative staging, are mandatory to pose indication for surgery in
      elderly. On the other hand, all elderly patients with lung cancer should have
      some form of assessment of physiologic age. As minimally invasive thoracic
      surgery has reduced the postoperative morbidity and has led to a decrease in the
      length of hospital stay, lobectomy remains the treatment of choice for early
      stage NSCLC in elderly patients. Discussion by experienced multidisciplinary team
      is the best approach to evaluate the advantages/disadvantages of each treatment
      modality in elderly patients with early-stage NSCLC. 

PMID- 26207244
TI  - Can venous thromboembolism navigate the prevention of cardiovascular
      complications?

PMID- 26207245
TI  - Arterial cardiovascular events and mortality following venous thromboembolism.

PMID- 26207246
TI  - Chromogranin A as a predictor of radiological disease progression in
      neuroendocrine tumours.
AB  - BACKGROUND: Chromogranin A (CgA) is the best established neuroendocrine
      biomarker. This study was aimed at investigating the prognostic value of CgA as a
      predictor of radiological disease progression in neuroendocrine tumour (NET)
      patients. METHODS: Patients with metastatic NETs and evidence of radiological
      progression (RP) according to RECIST 1.1 were identified from a NET database.
      Plasma CgA levels were measured 6 and 12 months before RP and at the event of RP.
      CgA was measured with the Supra-regional-Assay-Service radioimmunoassay
      (Hammersmith Hospital). RESULTS: A total of 152 patients were evaluated including
      91 midgut NETs and 61 pancreatic NETs (PNETs). Of these, 56 were G1 NETs, 65 G2,
      10 G3, 21 of unknown histology. For all NETs, there was a positive trend in terms
      of increase of CgA values 6 months prior to RP compared to 12 months before RP.
      Subgroup analysis at first episode of RP showed that for PNETs there was evidence
      of a difference in the median CgA levels. CgA 6 months before RP was 100 pmol/L
      [interquartile 1 (Q1) =53 and Q3 =286.25 pmol/L) and 12 months before was 52
      pmol/L (Q1 =36.25 and Q3 =128 pmol/L), W=52, P=0.48. This observation was not
      confirmed in midgut NETs, where median CgA 6 months before RP was 389.5 pmol/L
      (Q1 =131.5 and Q3 =791.5 pmol/L) and 12 months before was 319 pmol/L (Q1 =158 and
      Q3 =753 pmol/L), W=191, P=0.39]. Low grade tumours (G1) had a median CgA value at
      6 months significantly higher than at 12 months [181 (Q1 =56.25, Q3 =624) vs.
      149.5 (Q1 =44, Q3 =247.25) pmol/L, W=70, P=0.48]. CONCLUSIONS: CgA seems to have
      predictive value 6 months prior to RP for PNETs and G1 tumours. Further
      prospective analyses are needed to enable more definitive conclusions.

PMID- 26207247
TI  - Histopathological correlations of appendectomies: a clinical audit of a single
      center.
AB  - BACKGROUND: Acute appendicitis is a common presentation in surgical assessment
      units and appendectomy accounts for a large number of emergency operations in the
      UK. Histopathological examination of the appendectomy specimens are routinely
      carried out. The aim of this study is to correlate the histological findings of
      appendectomy specimens with the clinical diagnosis of acute appendicitis.
      METHODS: This is a retrospective analysis of 238 appendectomies carried out in a
      single UK center between January and December 2013. The Histopathology reports of
      appendectomy specimens were retrieved. RESULTS: A total of 238 appendectomies
      were performed during the study period. The mean age of the patients was 32 years
      (range, 7-81 years). Adult patients (>16 years) represented 79.4% of the study
      population. The female sex accounted for 46.6% of all the patients. Of the 238
      resected appendix, 211 (88.7%) had histopathology findings consistent with
      appendicitis. Approximately 1.7% of the 238 specimens were abnormal pathologies
      other than inflammation of the appendix. The negative appendectomy (normal
      appendix on histology) rate was 11.3%. The female sex accounted for 59.1% of the
      negative appendectomies. Adults (>16 years) represented 77.8% of the negative
      appendectomies. CONCLUSIONS: The observed high rates of negative appendectomy in
      the female sex can be reduced by utilizing combined clinical assessment and
      diagnostic imaging modalities. The findings of abnormal pathologies on
      histopathological examination of the appendix which could potentially impact on
      the management of the patients justify the current practice of routine
      histopathological examination of resected appendix.

PMID- 26207248
TI  - A sneak peak of the 2015 report on the market of type 2 diabetes mellitus
      diagnosis and treatment in China.
AB  - To understand the status quo of the diagnosis and treatment of type 2 diabetes
      mellitus (T2DM) in China. A total of 1,759 respondents from 31 provinces,
      municipalities, and autonomous regions participated this online questionnaire
      based survey from November to December in 2014 via the DXY.cn survey & research
      platform. All the respondents had certain experiences in T2DM management. Up to
      83% of the T2DM patients were re-visiting patients, in whom hyperlipidemia,
      hypertension, and neuropathy were the most common co-morbidities or
      complications. Fasting blood glucose, postprandial blood glucose, glycosylated
      hemoglobin were the most commonly used tests, while oral glucose tolerance test
      (OGTT) had also became one of the most common tests for new patients. Oral
      hypoglycemic agents remain the most widely used hypoglycemic treatment, with
      metformin, sulfonylureas, and glycosidase inhibitors being the top three oral
      antidiabetic drugs. Less than half (43%) of the T2DM patients were receiving
      insulin treatment, among which the premixed insulin was the most common type,
      followed by short-acting insulin, long-acting insulin, and medium-acting insulin.
      A certain percentage of patients were also using novel antidiabetic drugs
      including DPP-IV and GLP-1. Foreign pharmaceutical companies had the largest
      shares in most markets. However, domestic generic medicine had larger market
      shares in smaller cities (third- and lower-tier cities) than in major cities
      (first- and second-tier cities). 

PMID- 26207249
TI  - Current trends in the surgical management and treatment of adult glioblastoma.
AB  - This manuscript discusses the current surgical management of glioblastoma. This
      paper highlights the common pathophysiology attributes of glioblastoma, surgical
      options for diagnosis/treatment, current thoughts of extent of resection (EOR) of
      tumor, and post-operative (neo)adjuvant treatment. Glioblastoma is not a disease
      that can be cured with surgery alone, however safely performed maximal surgical
      resection is shown to significantly increase progression free and overall
      survival while maximizing quality of life. Upon invariable tumor recurrence, re
      resection also is shown to impact survival in a select group of patients. As
      adjuvant therapy continues to improve survival, the role of surgical resection in
      the treatment of glioblastoma looks to be further defined. 

PMID- 26207250
TI  - Dietary, non-microbial intervention to prevent Helicobacter pylori-associated
      gastric diseases.
AB  - Since the discovery of Helicobacter pylori (H. pylori) infection as the major
      cause of gastroduodenal disorders including acute and chronic gastritis,
      gastroduodenal ulcer, chronic atrophic gastritis, and gastric cancer almost three
      decades ago, the possibility of preventing these clinical diseases through
      eradicating H. pylori has been the focus of active research, but soon debate in
      the scientific community, though eradication opens the feasibility of cancer
      prevention and the removal of bacteria significantly prevents development or
      recurrence of peptic ulcer diseases and some clinical diseases, was proposed due
      to uncertainty in either achievement of complete eradication or inefficacy in
      cancer prevention with eradication alone. Still its linkage to gastric cancer is
      incontestable. Since the multiple combination of bacterial factors, environmental
      insults, and the host immune response that drives the initiation and progression
      of mucosal atrophy, metaplasia, and dysplasia toward gastric cancer is
      intervened, simple eradication deemed the feasibility of cancer prevention.
      Therefore, our group open strong hypothesis that non-microbial, dietary approach
      might be the alternate, for which several interventions of nutritional components
      can highlight rejuvenation of chronic atrophic gastritis as well as amelioration
      of H. pylori-associated procarcinogenic inflammation. In this review article, the
      experience and outcome regarding nutritional application to rejuvenate gastric
      atrophy will be introduced, using Korean red ginseng, garlic extracts, cancer
      preventive Korea kimchi, n-3 polyunsaturated fatty acids (PUFA), special form of
      licorice, and probiotics. The detailed influence of dietary intervention and
      bacterial eradication therapy on disease progression and reversibility of
      premalignant lesions are discussed. 

PMID- 26207252
TI  - Laparoscopic extended right hemicolectomy with D3 lymphadenectomy.

PMID- 26207253
TI  - Laparoscopic radical gastrectomy for gastric cancer: traps and strategies.

PMID- 26207251
TI  - The macrosphere model-an embolic stroke model for studying the pathophysiology of
      focal cerebral ischemia in a translational approach.
AB  - The main challenge of stroke research is to translate promising experimental
      findings from the bench to the bedside. Many suggestions have been made how to
      achieve this goal, identifying the need for appropriate experimental animal
      models as one key issue. We here discuss the macrosphere model of focal cerebral
      ischemia in the rat, which closely resembles the pathophysiology of human stroke
      both in its acute and chronic phase. Key pathophysiological processes such as
      brain edema, cortical spreading depolarizations (CSD), neuroinflammation, and
      stem cell-mediated regeneration are observed in this stroke model, following
      characteristic temporo-spatial patterns. Non-invasive in vivo imaging allows
      studying the macrosphere model from the very onset of ischemia up to late
      remodeling processes in an intraindividual and longitudinal fashion. Such a
      design of pre-clinical stroke studies provides the basis for a successful
      translation into the clinic. 

PMID- 26207254
TI  - Application of laparoscopy in the diagnosis and treatment of gastric cancer.

PMID- 26207255
TI  - Robotic thoracic surgery of the posterior superior mediastinal mass.

PMID- 26207256
TI  - Expert consensus on image-guided radiofrequency ablation of pulmonary tumors-2015
      edition.

PMID- 26207257
TI  - Professor Yin Li: "non-tube no fasting"-an innovative management of fast-track
      surgery in patients with esophageal cancer.

PMID- 26207258
TI  - Simple downstream process based on detergent treatment improves yield and in vivo
      transduction efficacy of adeno-associated virus vectors.
AB  - Recombinant adeno-associated viruses (rAAV) are promising candidates for gene
      therapy approaches. The last two decades were particularly fruitful in terms of
      processes applied in the production and purification of this type of gene
      transfer vectors. This rapid technological evolution led to better yields and
      higher levels of vector purity. Recently, some reports showed that rAAV produced
      by transient tri-transfection method in adherent human embryonic kidney 293 cells
      can be harvested directly from supernatant, leading to easier and faster
      purification compared to classical virus extraction from cell pellets. Here, we
      compare these approaches with new vector recovery method using small quantity of
      detergent at the initial clarification step to treat the whole transfected cell
      culture. Coupled with tangential flow filtration and iodixanol-based isopycnic
      density gradient, this new method significantly increases rAAV yields and
      conserves high vector purity. Moreover, this approach leads to the reduction of
      the total process duration. Finally, the vectors maintain their functionality,
      showing unexpected higher in vitro and in vivo transduction efficacies. This new
      development in rAAV downstream process once more demonstrates the great capacity
      of these vectors to easily accommodate to large panel of methods, able to
      furthermore ameliorate their safety, functionality, and scalability. 

PMID- 26207259
TI  - Integration of red cell genotyping into the blood supply chain: a population
      based study.
AB  - BACKGROUND: When problems with compatibility arise, transfusion services often
      use time-consuming serological tests to identify antigen-negative red cell units
      for safe transfusion. New methods have made red cell genotyping possible for all
      clinically relevant blood group antigens. We did mass-scale genotyping of donor
      blood and provided hospitals with access to a large red cell database to meet the
      demand for antigen-negative red cell units beyond ABO and Rh blood typing.
      METHODS: We established a red cell genotype database at the BloodCenter of
      Wisconsin on July 17, 2010. All self-declared African American, Asian, Hispanic,
      and Native American blood donors were eligible irrespective of their ABO and Rh
      type or history of donation. Additionally, blood donors who were groups O, A, and
      B, irrespective of their Rh phenotype, were eligible for inclusion only if they
      had a history of at least three donations in the previous 3 years, with one
      donation in the previous 12 months at the BloodCenter of Wisconsin. We did red
      cell genotyping with a nanofluidic microarray system, using 32 single nucleotide
      polymorphisms to predict 42 blood group antigens. An additional 14 antigens were
      identified via serological phenotype. We monitored the ability of the red cell
      genotype database to meet demand for compatible blood during 3 years. In addition
      to the central database at the BloodCenter of Wisconsin, we gave seven hospitals
      online access to a web-based antigen query portal on May 1, 2013, to help them to
      locate antigen-negative red cell units in their own inventories. FINDINGS: We
      analysed genotype data for 43,066 blood donors. Requests were filled for 5661
      (99.8%) of 5672 patient encounters in which antigen-negative red cell units were
      needed. Red cell genotyping met the demand for antigen-negative blood in 5339
      (94.1%) of 5672 patient encounters, and the remaining 333 (5.9%) requests were
      filled by use of serological data. Using the 42 antigens represented in our red
      cell genotype database, we were able to fill 14,357 (94.8%) of 15,140 requests
      for antigen-negative red cell units from hospitals served by the BloodCenter of
      Wisconsin. In the pilot phase, the seven hospitals identified 71 units from 52
      antigen-negative red cell unit requests. INTERPRETATION: Red cell genotyping has
      the potential to transform the way antigen-negative red cell units are provided.
      An antigen query portal could reduce the need for transportation of blood and
      serological screening. If this wealth of genotype data can be made easily
      accessible online, it will help with the supply of affordable antigen-negative
      red cell units to ensure patient safety. FUNDING: BloodCenter of Wisconsin
      Diagnostic Laboratories Strategic Initiative and the NIH Clinical Center
      Intramural Research Program.

PMID- 26207260
TI  - Mutations in Plasmalemma Vesicle Associated Protein Result in Sieving Protein
      Losing Enteropathy Characterized by Hypoproteinemia, Hypoalbuminemia, and
      Hypertriglyceridemia.
AB  - BACKGROUND & AIMS METHODS: Severe intestinal diseases observed in very young
      children are often the result of monogenic defects. We used whole exome
      sequencing (WES) to examine the genetic cause in a patient with a distinct severe
      form of protein losing enteropathy (PLE) characterized by hypoproteinemia,
      hypoalbuminemia, and hypertriglyceridemia. METHODS: WES was performed at the
      Centre for Applied Genomics, Hospital for Sick Children, Toronto, Canada. Exome
      library preparation was performed using the Ion Torrent AmpliSeq RDY Exome Kit.
      Functional studies were carried out based on the identified mutation. RESULTS:
      Using whole exome sequencing we identified a homozygous nonsense mutation
      (1072C>T; p.Arg358*) in the PLVAP (plasmalemma vesicle associated protein) gene
      in an infant from consanguineous parents who died at five months of age of severe
      protein losing enteropathy. Functional studies determined that the mutated PLVAP
      mRNA and protein were not expressed in the patient biopsy tissues, presumably
      secondary to nonsense-mediated mRNA decay. Pathological analysis showed that the
      loss of PLVAP resulted in disruption of endothelial fenestrated diaphragms.
      CONCLUSIONS: PLVAP p.Arg358* mutation resulted in loss of PLVAP expression with
      subsequent deletion of the diaphragms of endothelial fenestrae leading to plasma
      protein extravasation, protein-losing enteropathy and ultimately death.

PMID- 26207261
TI  - Plasma BDNF levels associate with Pittsburgh compound B binding in the brain.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in
      Alzheimer's disease (AD) and other neurodegenerative disorders. BDNF function is
      adversely affected by amyloid beta (Abeta) in AD. BDNF levels in brain and
      peripheral tissues are lower in patients with AD and MCI, than in controls. Here
      we examined the association between plasma levels of BDNF and amyloid deposition
      in the brain measured with Pittsburgh Compound B (PiB). METHOD: Our dataset
      consisted of 18 AD, 56 mild cognitive impairment (MCI) and 3 normal control (NC)
      Alzheimer's Disease Neuroimaging Initiative-1 (ADNI1) subjects with available
      [11C] PiB and peripheral blood protein data. MRI-coregistered PET data was
      smoothed with a 15 mm kernel and mapped onto 3D hemispheric models using the
      warping deformations computed in cortical pattern matching of the associated MRI
      scans. We applied linear regression to examine in 3D the associations between
      BDNF and PiB SUVR, while adjusting for age and sex. We used permutation
      statistics thresholded at p<0.01 for multiple comparisons correction. RESULTS:
      Plasma BDNF levels showed significant negative associations with left greater
      than right amyloid burden in the lateral temporal, inferior parietal, inferior
      frontal, anterior and posterior cingulate, and orbitofrontal regions (left
      pcorrected=0.03). CONCLUSIONS: As hypothesized, lower plasma levels of BDNF were
      significantly associated with widespread brain amyloidosis.

PMID- 26207263
TI  - Automatic Population HARDI White Matter Tract Clustering by Label Fusion of
      Multiple Tract Atlases.
AB  - Automatic labeling of white matter fibres in diffusion-weighted brain MRI is
      vital for comparing brain integrity and connectivity across populations, but is
      challenging. Whole brain tractography generates a vast set of fibres throughout
      the brain, but it is hard to cluster them into anatomically meaningful tracts,
      due to wide individual variations in the trajectory and shape of white matter
      pathways. We propose a novel automatic tract labeling algorithm that fuses
      information from tractography and multiple hand-labeled fibre tract atlases. As
      streamline tractography can generate a large number of false positive fibres, we
      developed a top-down approach to extract tracts consistent with known anatomy,
      based on a distance metric to multiple hand-labeled atlases. Clustering results
      from different atlases were fused, using a multi-stage fusion scheme. Our "label
      fusion" method reliably extracted the major tracts from 105-gradient HARDI scans
      of 100 young normal adults.

PMID- 26207262
TI  - Stereopsis is adaptive for the natural environment.
AB  - Humans and many animals have forward-facing eyes providing different views of the
      environment. Precise depth estimates can be derived from the resulting binocular
      disparities, but determining which parts of the two retinal images correspond to
      one another is computationally challenging. To aid the computation, the visual
      system focuses the search on a small range of disparities. We asked whether the
      disparities encountered in the natural environment match that range. We did this
      by simultaneously measuring binocular eye position and three-dimensional scene
      geometry during natural tasks. The natural distribution of disparities is indeed
      matched to the smaller range of correspondence search. Furthermore, the
      distribution explains the perception of some ambiguous stereograms. Finally,
      disparity preferences of macaque cortical neurons are consistent with the natural
      distribution.

PMID- 26207264
TI  - [In Process Citation].

PMID- 26207265
TI  - Career advancement: Insider knowledge.

PMID- 26207266
TI  - Cerebrospinal fluid had come a long way since Galen of  Pergamon (130-200)
      declared the ventricles to be reservoirs  for the animal spirits.

PMID- 26207267
TI  - Specific muscle-tendon architecture in elite Kenyan distance runners.
AB  - The Achilles tendon moment arm (MA_AT) and foot lever ratio (FLR) can play
      important roles for force production and movement economy during locomotion. This
      notion has become more relevant, and suggestion has been given that the Kenyan
      runners belonging to the world elite would have specific anatomical, mechanical,
      and functional properties in their lower limbs and that this feature could be
      responsible for their high running economy. The present study aimed to
      characterize the AT of elite Kenyan distance runners as compared with Japanese
      ones, and to examine the potential relationship with their running performance.
      Ultrasonography was used to measure AT cross-sectional area and AT soleus and
      gastrocnemius lengths. MA_AT and FLR were calculated from the position of
      anatomical landmarks using sagittal plane photographs. MA_AT was significantly
      longer and the FLR lower in Kenyans than in Japanese. Independently of the group,
      the running performance was positively related to the MA_AT (r = 0.55, P < 0.001)
      and negatively to the FLR (r = -0.45, P = 0.002). These results suggest that
      longer MA_AT and lower FLR could be advantageous in elite Kenyan runners, by
      contributing to effective endurance running performance in a protective and
      economical way.

PMID- 26207268
TI  - The rise (and fall?) of drug discrimination research.

PMID- 26207269
TI  - Determining place and process: functional traits of ectomycorrhizal fungi that
      affect both community structure and ecosystem function.
AB  - There is a growing interest amongst community ecologists in functional traits.
      Response traits determine membership in communities. Effect traits influence
      ecosystem function. One goal of community ecology is to predict the effect of
      environmental change on ecosystem function. Environmental change can directly and
      indirectly affect ecosystem function. Indirect effects are mediated through
      shifts in community structure. It is difficult to predict how environmental
      change will affect ecosystem function via the indirect route when the change in
      effect trait distribution is not predictable from the change in response trait
      distribution. When response traits function as effect traits, however, it becomes
      possible to predict the indirect effect of environmental change on ecosystem
      function. Here we illustrate four examples in which key attributes of
      ectomycorrhizal fungi function as both response and effect traits. While plant
      ecologists have discussed response and effect traits in the context of community
      structuring and ecosystem function, this approach has not been applied to
      ectomycorrhizal fungi. This is unfortunate because of the large effects of
      ectomycorrhizal fungi on ecosystem function. We hope to stimulate further
      research in this area in the hope of better predicting the ecosystem- and
      landscape-level effects of the fungi as influenced by changing environmental
      conditions.

PMID- 26207270
TI  - Patient Safety--What Is Your Role?

PMID- 26207271
TI  - Safety: A Health Care Priority.

PMID- 26207272
TI  - Professionalism and Nephrology Nursing.

PMID- 26207273
TI  - Patient Safety and Patient Safety Culture in Nephrology Nurse Practice Settings:
      Issues, Solutions, and Best Practices.
AB  - In order to assure patient safety, it is necessary to create positive patient
      safety cultures. This article presents the initial qualitative results from a
      national study, "Patient Safety Culture in Nephrology Nurse Practice Settings."
      Based on the responses of participants, themes were identified for both issues
      and potential solutions and best practices. Issue themes included underreporting
      of events and near misses, poor staffing ratios, long work hours, communication
      lapses, and training, infection control, and compliance. Potential solutions and
      best practice themes included non-punitive and transparent event reporting, fall
      reduction strategies, improved medication administration practices, and scheduled
      safety huddles and safety meetings. The results of this landmark study can be
      used to start conversations and spark education programs to improve patient
      safety culture in nephrology nurse practice settings.

PMID- 26207274
TI  - Nurse Manager Safety Practices in Outpatient Hemodialysis Units.
AB  - Little is known regarding the specific managerial activities or best practices
      that nurse managers in outpatient hemodialysis settings use to achieve positive
      safety outcomes. The purpose of this study was to identify and describe specific
      managerial practices used by nurse managers in outpatient hemodialysis units to
      enhance patient safety and quality of care. A descriptive qualitative design was
      used. Seventeen nurse managers in outpatient hemodialysis units comprised the
      study sample. Telephone interviews were conducted, and qualitative content
      analysis was used to encode the data. Nurse managers identified patients, staff,
      the dialysis unit environment, and the dialysis organization as sources of safety
      risks. Nurse manager safety practices illuminated from the data were complex and
      multifaceted, and were aimed at reducing patient, staff environmental, and
      organization risks. The findings from this study offer a description and a better
      understanding of the practices in which nurse managers in outpatient hemodialysis
      units engage to keep patients safe in their units, and they underscore the
      critical role of nurse managers in creating and maintaining patient safety within
      outpatient hemodialysis settings.

PMID- 26207276
TI  - A Paradigm Shift in Options, Education, and an Online Decision Aid: 'My Life, My
      Dialysis Choice'.
AB  - Dialysis options education in the United States for patients tends to focus on
      clinical aspects of ESRD treatment and on how each option is done. The non-profit
      Medical Education Institute (MEI) has developed an online, patient-centered
      dialysis decision aid that maps six dialysis options (peritoneal dialysis,
      standard incenter hemodialysis, conventional home hemodialysis, short daily
      hemodialysis, and nocturnal hemodialysis--incenter or at home) in four categories
      onto 24 different lifestyle and health values. This new free, non-commercial tool
      allows education to start with why an individual might want to choose a
      particular option, rather than how, a paradigm shift that may enable more
      effective options education.

PMID- 26207275
TI  - Using High-Fidelity Simulation to Assess Knowledge, Skills, and Attitudes in
      Nurses Performing CRRT.
AB  - Continuous renal replacement therapy (CRRT) is an acute therapy for critically
      ill patients. There are many life-threatening complications that can occur;
      therefore, it is imperative that nurses are highly trained in the use and
      troubleshooting of CRRT. A structured simulation exercise was added to an
      existing CRRT education program by developing and implementing an annual
      assessment of knowledge, skills, and attitudes (KSAs) using high-fidelity
      simulation. The use of high-fidelity simulation as an intervention during annual
      evaluation of KSAs was shown to be effective in increasing nurse satisfaction,
      understanding of CRRT principles, and critical thinking skills with the operation
      of CRRT.

PMID- 26207277
TI  - Intradialytic Hypotension Prevention and Management Knowledge and Practices:
      Results from a Survey of Australian and New Zealand Nephrology Nurses.
AB  - Intradialytic hypotension (IDH) remains the most frequent serious side effect of
      hemodialysis, increasing morbidity in patients on hemodialysis. Nephrology nurses
      have a critical role in the prevention and management of IDH. The aim of this
      study was to investigate nephrology nurse knowledge and practice habits in the
      prevention and management of IDH. This was an explorative cross-sectional design,
      web-based survey of Australian and New Zealand nephrology nurses (n = 173). IDH
      definitions, blood pressure interpretation, and IDH interventions were
      inconsistent and not always evidence-based. Demographic characteristics had
      little impact on the variation in responses. A universal definition for IDH may
      improve early recognition of the problem. Formal guidelines in considering
      individualized interventional strategies for asymptomatic episodes prior
      symptomatic IDH occurrence may improve outcomes for patients on hemodialysis.

PMID- 26207278
TI  - The culture of safety in dialysis settings.

PMID- 26207279
TI  - Placing Patients with Hypertension at the Center of Self-Management and Research.

PMID- 26207280
TI  - Simplifying Dialysis Dose Measurement in the Hospital Setting: Kt/V Ionic
      Dialysance (ID) versus Kt/V(urea).

PMID- 26207281
TI  - Near Misses and Close Calls: What They Are and Why You Should Report Them.

PMID- 26207282
TI  - Lifelong Learning and Nephrology Nursing.

PMID- 26207283
TI  - Evidence-Based Interventions for Prevention of Bone Density Loss after Kidney
      Transplant.
AB  - Mineral and bone disorder is common in individuals with kidney transplant as a
      sequelae of chronic kidney disease. Rapid bone density loss that occurs during
      the first year after transplant along with pre-existing bone disorder, places
      these patients at risk of bone fractures at three times higher than the general
      population. This article examines the efficacy of current evidence-based clinical
      interventions in reducing the incidence of bone fractures among recipients of
      kidney transplant.

PMID- 26207284
TI  - Patient Safety Culture in Nephrology Nurse Practice Settings: Results by Primary
      Work Unit, Organizational Work Setting, and Primary Role.
AB  - Patient safety culture is critical to the achievement of patient safety. In 2014,
      a landmark national study was conducted to investigate patient safety culture in
      nephrology nurse practice settings. In this secondary analysis of data from that
      study, we report the status of patient safety culture by primary work unit
      (chronic hemodialysis unit, acute hemodialysis unit, peritoneal dialysis unit)
      and organizational work setting (for-profit organization, not-for-profit
      organization), and compare the perceptions of direct care nurses and
      managers/administrators on components of patient safety culture.

PMID- 26207285
TI  - Nursing Intervention Aimed at Improving Self-Managementfor Persons with Chronic
      Kidney Disease in North Carolina Medicaid: A Pilot Project.
AB  - This pilot project aimed to improve knowledge and self-management among Medicaid
      beneficiaries with Stage 3b and 4 chronic kidney disease who were identified
      using a population-based approach. Participants received up to six in-person
      educational sessions delivered by a nurse practitioner. Increases in knowledge
      and self-reported behavior changes were generally observed among participants.

PMID- 26207286
TI  - Development and Initial Validation of the NephRN Perceptions Toward Advance Care
      Planning Instrument.
AB  - The purpose of this study was to develop and pilot test an instrument to measure
      the perceptions of nephrology nurses toward advance care planning, the NephRN
      Perceptions Toward Advance Care Planning instrument. Four components of advance
      care planning were identified: knowledge, attitudes, comfort, and support. The
      four-component solution explained 63.88% of variance. Cronbach's alpha was 0.92,
      and subscale reliability ranged between 0.86 and 0.94. This instrument shows
      promise as a reliable and valid measure of nephrology nurse perceptions toward
      advance care planning for persons with chronic kidney disease.

PMID- 26207287
TI  - Prevalence of Depressive Symptoms and Associated Factors in People with Low
      Estimated Glomerular Filtration Rate: Findings from a South Korea National
      Survey.
AB  - This study explored the prevalence and factors associated with depressive
      symptoms in people with low estimated glomerular filtration rate (eGFR less than
      60 mL/min/1.73m2) using South Korea national survey data from 2008 to 2011.
      Multiple logistic regression analyses were employed to assess the associated
      factors of depressive symptoms in people with low eGFR. Among 25,324 study
      participants, 2.9% (n = 723) of all participants had low eGFR, and 16.7% (n =
      121) of these participants were self-reported to have depressive symptoms in the
      low eGFR group. The factors associated with depressive symptoms were higher
      psychological stress level (adjusted OR = 5.35, 95% CI = 3.01 to 9.52) and the
      lowest eGFR quartile (adjusted OR = 3.45, 95% CI = 1.48 to 8.01). This study
      suggests that the development and implementation of multifaceted nursing
      interventions for reducing psychological stress and managing reduced kidney
      function may be crucialfor persons with low eGFR to prevent or ameliorate
      depressive symptoms.

PMID- 26207288
TI  - IV Iron: To Give or to Hold in the Presence of Infection in Adults Undergoing
      Hemodialysis.
AB  - Intravenous (IV) iron is often given to treat iron deficiency anemia in adults
      undergoing hemodialysis. Evidence supports an association between IV iron and
      infection exits, which often create a clinical dilemma: whether to give or to
      hold in the presence of infection. This article presents the best available
      evidence regarding the risk of IV iron and infection along with nephrology
      nursing practice implications.

PMID- 26207289
TI  - The Progression of Kidney Disease in Patients with HIV.

PMID- 26207290
TI  - Nephrology Advanced Practice Registered Nurse Health Policy: Where Are We? What
      Is Our Future?

PMID- 26207291
TI  - Atypical teratoid/ rhabdoid tumor, an immunohistochemical study of potential
      diagnostic and prognostic markers.
AB  - Atypical teratoid/rhabdoid tumor (AT/RT) is a rare tumor of the CNS mostly seen
      in infants and is often associated with a dismal outcome. Despite the
      heterogeneous morphology and/or immunoprofile, its diagnosis nowadays relies on
      the negative INI-1/BAF47 nuclear immunostain in tumor cells. We aim to
      investigate a number of immunohistochemical antibodies as potential diagnostic
      and prognostic markers. All AT/RT cases in patients younger than 18 years of age
      were included. Demographics, clinical features and outcome were collected.
      Immunostains tested included SALL-4, OCT3/4, CD99, FLI-1, cyclin-D1, beta
      catenin, P53, P16, CDX2 and WT-1. Nineteen cases (10 males) were identified at
      our center between 2004-2013 with a median age of 24 months. Ten (52.6%) cases
      were supratentorial. Six (42.9%) cases showed metastasis at time of presentation.
      Chemotherapy was administered to 10 (62.5%) and radiotherapy to seven (43.8%).
      The median overall survival was 11 months. A single long-term survival of 104
      months was identified. Pathologically, most cases showed an admixture of rhabdoid
      cells and/or small cells and/or pale cells in variable proportions. Of all tested
      antibodies, only positivity for FLI-1 was associated with improved survival (P =
      0.0012), while positivity for cyclin-D1 showed a trend toward improved survival
      (P = 0.0547). CDX2 was positive only in the single long-term survival.
      Interestingly, two cases showed co-expression of CD99 and FLI-1, and some were
      positive for SALL-4. In conclusion, FLI-1 and cyclin-D1 are potential prognostic
      markers associated with better outcome. Occasional AT/RT cases might co-express
      CD99 and FLI-1 as well as SALL-4, a potential diagnostic pitfall with Ewing
      sarcoma/ primitive neuroectodermal tumors and germ cell tumors, respectively. 

PMID- 26207292
TI  - Antibiotic Resistance in the Environment: Not the Usual Suspects.
AB  - In this issue of Chemistry & Biology, Forsberg et al. (2015) show how
      metagenomics and biological chemistry can be combined to discover new classes of
      antibiotic resistance from soil metagenomes. The authors specifically reveal
      previously unseen resistance mechanisms and genes evident in soils, which will
      better inform both environmental and clinical studies on antibiotic resistance.

PMID- 26207293
TI  - Increasing the Diversity of Known Pictet-Spenglerases.
AB  - Pictet-Spenglerases catalyze key condensation/cyclization reactions between
      aromatic ethylamines and aldehydes in the biosynthesis of alkaloids. In this
      issue of Chemistry & Biology, Mori et al. (2015) report the structural
      elucidation of a novel type of Pictet-Spenglerase involved in the biosynthesis of
      the beta-carboline alkaloids.

PMID- 26207294
TI  - Expanding the Toolkit for the Serine Hydrolases.
AB  - In this issue of Chemistry & Biology, Cognetta et al. (2015) describe new
      pharmacological tools, including N-hydroxyhydantoin-containing carbamate
      inhibitors and an activity-based probe, for palmitoyl protein thioesterase 1 and
      alpha, beta-hydrolase domain-4 that expand the toolkit for the serine hydrolases.

PMID- 26207295
TI  - DNMT1 and Cancer: An Electrifying Link.
AB  - Aberrant epigenetic methylation is linked to the onset and progression of cancer.
      In this issue of Chemistry & Biology, Furst and Barton (2015) describe a
      sensitive electrochemical assay that can detect hyperactive epigenetic
      methylation in tumor tissue. 

PMID- 26207296
TI  - Longitudinal patterns of change in eye-hand coordination in children aged 8-16
      years.
AB  - Enhanced eye-hand coordination (EHC) is associated with greater participation in
      physical activity. No longitudinal studies have examined the change in throw
      catch EHC from childhood to mid-adolescence. We investigated the development of
      EHC with an object control test from childhood to mid-adolescence in boys and
      girls. Evaluated at age 8, 10, 12 and 16 years, EHC was measured as the aggregate
      success rate of a throw and wall-rebound catch test. The test involved 40
      attempts of progressive increasing difficulty, as determined by increased
      distances from a wall and transitions from two-handed to one-handed catches.
      Outcomes were treated as quasi-binomial and modelled by generalised linear mixed
      logistic regression analysis. EHC improved with age from childhood to mid
      adolescence, although boys were more adept at each age (p<0.001). The patterns of
      change in EHC with increasing age varied according to the degree of difficulty of
      the task (p<0.001); throw and two-handed catch proficiency developing earlier
      than throw and one-handed catch in both sexes. Boys' EHC was better than girls'
      as early as age 8 years and male proficiency was maintained through to mid
      adolescence. The proficiency of throw and two-handed catch rates developed faster
      than throw and one-handed catch rates for both sexes.

PMID- 26207297
TI  - Thoracoschisis: A Case Report and Review of Literature.
AB  - Thoracoschisis is an extremely rare congenital birth defect in which intra
      abdominal organs eviscerate through a defect in the thoracic wall(1). There are
      only seven previously reported pediatric cases and in each case, there is some
      diaphragmatic anomaly, suggesting that the defect took place before complete
      formation of the diaphragm. Our patient was referred to us from a local hospital
      immediately after delivery. The patient was born with a thoracoschisis of the
      left side below the 8(th) intercostal space. The thoracoschisis was repaired.
      Although there is a high prevalence of cardiac defects among thoracoschisis
      patients, this patient shows only small atrial septal defects.

PMID- 26207298
TI  - Influence of next-generation sequencing and storage conditions on miRNA patterns
      generated from PAXgene blood.
AB  - Whole blood derived miRNA signatures determined by Next-Generation Sequencing
      (NGS) offer themselves as future minimally invasive biomarkers for various human
      diseases. The PAXgene system is a commonly used blood storage system for miRNA
      analysis. Central to all miRNA analyses that aim to identify disease specific
      miRNA signatures, is the question of stability and variability of the miRNA
      profiles that are generated by NGS. We characterized the influence of five
      different conditions on the genome wide miRNA expression pattern of human blood
      isolated in PAXgene RNA tubes. In detail, we analyzed 15 miRNomes from three
      individuals. The blood was subjected to different numbers of freeze/thaw cycles
      and analyzed for the influence of storage at -80 or 8  degrees C. We also
      determined the influence of blood collection and NGS preparations on the miRNA
      pattern isolated from a single individual, which has been sequenced 10 times.
      Here, five PAXGene tubes were consecutively collected that have been split in two
      replicates, representing two experimental batches. All samples were analyzed by
      Illumina NGS. For each sample, approximately 20 million NGS reads have been
      generated. Hierarchical clustering and Principal Component Analysis (PCA) showed
      an influence of the different conditions on the miRNA patterns. The effects of
      the different conditions on miRNA abundance are, however, smaller than the
      differences that are due to interindividual variability. We also found evidence
      for an influence of the NGS measurement on the miRNA pattern. Specifically, hsa
      miR-1271-5p and hsa-miR-182-5p showed coefficients of variation above 100%
      indicating a strong influence of the NGS protocol on the abundance of these
      miRNAs. 

PMID- 26207300
TI  - Protein Composition of TGFBI-R124C- and TGFBI-R555W-Associated Aggregates
      Suggests Multiple Mechanisms Leading to Lattice and Granular Corneal Dystrophy.
AB  - PURPOSE: Transforming growth factor beta-induced (TGFBI)-related dystrophies
      constitute the most common heritable forms of corneal dystrophy worldwide.
      However, other than the underlying genotypes of these conditions, a limited
      knowledge exists of the exact pathomechanisms of these disorders. This study
      expands on our previous research investigating dystrophic stromal aggregates,
      with the aim of better elucidating the pathomechanism of two conditions arising
      from the most common TGFBI mutations: granular corneal dystrophy type 1 (GCD1;
      R555W) and lattice corneal dystrophy type 1 (LCD1; R124C). METHODS: Patient
      corneas with GCD1 and LCD1 were stained with hematoxylin and eosin and Congo red
      to visualize stromal nonamyloid and amyloid deposits, respectively. Laser capture
      microdissection was used to isolate aggregates and extracted protein was analyzed
      by mass spectrometry. Proteins were identified and their approximate abundances
      were determined. Spectra of TGFBIp peptides were also recorded and quantified.
      RESULTS: In total, three proteins were found within GCD1 aggregates that were
      absent in the healthy control corneal tissue. In comparison, an additional 18 and
      24 proteins within stromal LCD1 and Bowman's LCD1 deposits, respectively, were
      identified. Variances surrounding the endogenous cleavage sites of TGFBIp were
      also noted. An increase in the number of residues experiencing cleavage was
      observed in both GCD1 aggregates and LCD1 deposits. CONCLUSIONS: The study
      reveals previously unknown differences between the protein composition of GCD1
      and LCD1 aggregates, and confirms the presence of the HtrA1 protease in LCD1
      amyloid aggregates. In addition, we find mutation-specific differences in the
      processing of mutant TGFBIp species, which may contribute to the variable
      phenotypes noted in TGFBI-related dystrophies.

PMID- 26207299
TI  - Development of Animal Models of Local Retinal Degeneration.
AB  - PURPOSE: Development of nongenetic animal models of local retinal degeneration is
      essential for studies of retinal pathologies, such as chronic retinal detachment
      or age-related macular degeneration. We present two different methods to induce a
      highly localized retinal degeneration with precise onset time, that can be
      applied to a broad range of species in laboratory use. METHODS: A 30-MUm thin
      polymer sheet was implanted subretinally in wild-type (WT) rats. The effects of
      chronic retinal separation from the RPE were studied using histology and
      immunohistochemistry. Another approach is applicable to species with avascular
      retina, such as rabbits, where the photoreceptors and RPE were thermally ablated
      over large areas, using a high power scanning laser. RESULTS: Photoreceptors
      above the subretinal implant in rats degenerated over time, with 80% of the outer
      nuclear layer disappearing within a month, and the rest by 3 months. Similar loss
      was obtained by selective photocoagulation with a scanning laser. Cells in the
      inner nuclear layer and ganglion cell layer were preserved in both cases.
      However, there were signs of rewiring and decrease in the size of the bipolar
      cell terminals in the damaged areas. CONCLUSIONS: Both methods induce highly
      reproducible degeneration of photoreceptors over a defined area, with complete
      preservation of the inner retinal neurons during the 3-month follow-up. They
      provide a reliable platform for studies of local retinal degeneration and
      development of therapeutic strategies in a wide variety of species.

PMID- 26207301
TI  - Objective Analysis of Hyperreflective Outer Retinal Bands Imaged by Optical
      Coherence Tomography in Patients With Stargardt Disease.
AB  - PURPOSE: To develop and apply an objective algorithm for analyzing outer retinal
      layers imaged by spectral-domain optical coherence tomography (SD-OCT) in
      patients with Stargardt disease (STGD1). METHODS: Horizontal macular B-scans were
      acquired from 20 visually normal controls and 20 genetically confirmed stage 1
      STGD1 patients. The number of outer retinal bands was quantified using a
      semiautomated algorithm that detected bands using the second derivative of
      longitudinal reflectivity profiles. The present analysis focused on the three
      outermost bands, currently associated with the ellipsoid zone (EZ), cone outer
      segment interdigitation zone (IZ), and retinal pigment epithelium (RPE) complex.
      RESULTS: The RPE complex and EZ bands were detected throughout the B-scan in all
      controls. The RPE complex was detected throughout the B-scan in all patients, but
      was atrophic appearing in some locations. The EZ band was detected only outside
      the central lesion. Interdigitation zone band detection varied as a function of
      eccentricity for both groups, with detection for controls being highest in the
      para- and perifovea and lowest in the fovea and near periphery. In patients, the
      IZ band was generally not present in the fovea or para- or perifovea due to the
      central lesion. Outside of the lesion, the IZ band was detected in 26% of
      patients (mean detection across the near periphery), which was approximately half
      of the detection in controls. CONCLUSIONS: An objective approach for quantifying
      the number of outer retinal OCT bands found reduced IZ detection in STGD1
      patients. This occurred even outside the central lesion, demonstrating an
      inability to image the IZ, possibly due to enhanced RPE reflectivity or abnormal
      outer retinal structure.

PMID- 26207302
TI  - Impact of Macular Pigment on Fundus Autofluorescence Lifetimes.
AB  - PURPOSE: To characterize the macular region and to investigate the influence of
      the macular pigment (MP) on fundus autofluorescence (FAF) lifetimes in vivo.
      METHODS: Forty-eight healthy subjects with a mean age of 24.1 +/- 3.6 years
      (range, 20-37 years) were included. A 30 degrees  retinal field was investigated
      using the fluorescence lifetime imaging ophthalmoscope (FLIO), based on a
      Heidelberg Engineering Spectralis system, detecting FAF decays in a short (498
      560 nm; ch1)- and a long (560-720 nm; ch2)-wavelength channel. The mean
      fluorescence lifetime taum was calculated from a 3-exponential approximation of
      the FAF decays. Macular pigment optical density (MPOD) was measured by one
      wavelength reflectometry, and macular optical coherence tomogram (OCT) scans were
      recorded. Correlations between taum and MPOD were analyzed. RESULTS: The taum
      showed shortest values at the macular region with a mean of 82 ps (ch1) and 126
      ps (ch2). We found a strong correlation of taum to the MPOD (ch1: r = -0.760;
      ch2: r = -0.663; P < 0.001), as well as a topologic agreement of shortest taum
      with highest MPOD. CONCLUSIONS: Macular pigment, which is known to have very
      short fluorescence decays, considerably contributes to the macular
      autofluorescence (AF). This study gives indirect evidence for a strong impact of
      MP on macular taum, although no direct measurement of MP autofluorescence
      lifetimes in vivo is possible at this point. Potentially, imaging the FAF
      lifetimes could lead to a novel methodology for the detection of macular pigment
      properties and pathology-induced changes in the living human retina.

PMID- 26207303
TI  - Using Flickering Light to Enhance Nonimage-Forming Visual Stimulation in Humans.
AB  - PURPOSE: Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate
      nonimage-forming visual functions such as pupillary constriction and circadian
      photoentrainment. Optimizing daytime nonimage-forming photostimulation has health
      benefits. We aimed to enhance ipRGC excitation using flickering instead of steady
      light. METHODS: Human subjects were tested with a three-dimensional matrix of
      flickering 463-nm stimuli: three photon counts (13.7, 14.7 and 15.7 log photons
      cm(-2)), three duty cycles (12%, 47%, and 93%) and seven flicker frequencies
      (0.1, 0.25, 0.5, 1, 2, 4, and 7 Hz). Steady-state pupil constrictions were
      measured. RESULTS: Among stimuli containing 13.7 log photons cm-2, the one
      flickering at 2 Hz with a 12% duty cycle evoked the greatest pupil constriction
      of 48% +/- 4%, 71% greater than that evoked by an equal-intensity (12.3 log
      photons cm(-2) s(-1)) continuous light. This frequency and duty cycle were also
      best for 14.7 log photons cm-2 stimuli, inducing a 58% +/- 4% constriction which
      was 38% more than that caused by an equal-intensity (13.3 log photons cm(-2) s(
      1)) constant light. For 15.7 log photons cm-2 stimuli, the 1-Hz, 47% duty cycle
      flicker was optimal although it evoked the same constriction as the best 14.7 log
      photons cm(-2) flicker. CONCLUSIONS: Pupillary constriction depends on flicker
      frequency and duty cycle besides intensity. Among the stimuli tested, the one
      with the lowest photon count inducing a maximal response is 13.3 log photons cm(
      2) s(-1) flickering at 2 Hz with 12% duty cycle. Our data could guide the design
      of healthier architectural lighting and better phototherapy devices for treating
      seasonal affective disorder and jet lag.

PMID- 26207305
TI  - Human Umbilical Cord Lining Cells as Novel Feeder Layer for Ex Vivo Cultivation
      of Limbal Epithelial Cells.
AB  - PURPOSE: To determine the effectiveness of human umbilical cord-derived mucin
      expressing cord lining epithelial cells (CLEC-muc) as feeder cells in a coculture
      system for the cultivation of human limbal stem cells. METHODS: Human CLEC-muc
      were cultured in PTTe-1 medium and treated with mitomycin C to arrest their
      growth to make the feeder layer. Single-cell suspension of limbal cells was
      prepared from corneal rim collected from the Singapore Eye Bank. Limbal cells
      were cultured in a coculture system with CLEC-muc as well as 3T3 cells as feeder
      layer. We compared the colony-forming efficiency and cell morphology of the
      limbal cells cultured in the two different feeder layers. We also compared the
      expression level of several putative limbal stem cell markers, such as HES1,
      ABCG2, DeltaNP63, and BMI1, in the cultured limbal cells by immunostaining and
      quantitative (q)RT-PCR. Expression of cytokeratins CK14, CK15, CK19, CK3, and CK4
      was further compared. RESULTS: Human limbal epithelial cells cultured in both
      types of feeder layers showed comparable cell morphology and colony-forming
      efficiency. These cells exhibited a similar expression pattern of HES1, ABCG2,
      DeltaNP63, BMI1, CK14, CK15, CK19, and CK3 as detected by immunostaining and PCR.
      CONCLUSIONS: Human CLEC-muc may be a suitable alternative to conventional mouse
      3T3 feeder cells, which may reduce the risk of zoonotic infection.

PMID- 26207306
TI  - In Vivo and In Vitro Feasibility Studies of Intraocular Use of Polyethylene
      Glycol-Based Synthetic Sealant to Close Retinal Breaks in Porcine and Rabbit
      Eyes.
AB  - PURPOSE: Absorbable polyethylene glycol-based synthetic sealant (PEG sealant)
      polymerizes under xenon illumination and forms a clear, flexible, and firmly
      adherent hydrogel. The intraocular biocompatibility of PEG sealant and efficacy
      for closing retinal breaks were evaluated. METHODS: In an in vitro study, retinal
      detachment with a tear was created in porcine eyecups after vitreous gel removal.
      Polyethylene glycol-based synthetic sealant was applied to cover the tear and
      polymerized with a 40-second application of xenon light. Retinal adhesion
      strength was tested by forcefully squirting balanced salt solution (BSS) onto the
      retinal tear. Polyethylene glycol-based synthetic sealant was soaked in the BSS,
      incubated at 37 degrees C, and the pH measured periodically over 72 hours. In an
      in vivo study, PEG sealant was injected into the vitreous cavity of the left eyes
      of rabbits. Ophthalmologic examinations were performed and bilateral ERGs were
      recorded simultaneously before and 28 days after injection. The eyes were
      enucleated for histological evaluation. RESULTS: Adhesion of PEG sealant to the
      retina was good in BSS. A forceful squirt of BSS onto the retinal tear covered
      with PEG sealant did not detach the retina; the retinal tear without PEG sealant
      detached immediately. The pH of the BSS containing PEG sealant was between 7.2
      and 8.2. No inflammatory reaction was observed in the eyes throughout 28 days of
      follow-up. The ERGs recorded before and after injection showed typical patterns.
      Histological examinations did not reveal any abnormality or inflammation.
      CONCLUSIONS: Polyethylene glycol-based synthetic sealant appeared to effectively
      seal retinal breaks and was not toxic to the eye.

PMID- 26207304
TI  - Bacteria Colonizing the Ocular Surface in Eyes With Boston Type 1
      Keratoprosthesis: Analysis of Biofilm-Forming Capability and Vancomycin
      Tolerance.
AB  - PURPOSE: To analyze the bacterial microbiota colonizing the ocular surface of
      patients with Boston type 1 keratoprostheses (K-Pros) for antibacterial
      resistance patterns and capacity to form biofilms. METHODS: Twenty-seven eyes
      with a Boston type 1 K-Pro and 16 fellow control eyes from 26 patients were
      enrolled. The surface of the K-Pro optic and/or the inferior conjunctival fornix
      was swabbed and plated separately on culture media. Positive cultures were
      processed to assess for biofilm-forming capability. Microtiter plate adherence
      assay and polymerase chain reaction for ica and atlE genes were used. An in vitro
      assay of vancomycin tolerance was performed on isolated strains and compared to
      standard controls with and without biofilm-forming capability. RESULTS: Eighty
      five percent of K-Pro eyes and 69% of control eyes had positive cultures (P =
      0.20). All Gram-positive strains exhibited susceptibility to vancomycin by
      standard testing. Biofilm-forming bacterial isolates were detected in 57.7% of K
      Pro eyes and 53.3% of control eyes. A vancomycin tolerance assay showed that the
      antibiotic susceptibility of coagulase-negative staphylococcus (CNS) within
      biofilms was significant in only three of five biofilm-forming strains (P <
      0.05). In all strains, bacterial cells in planktonic form were more susceptible
      to vancomycin than in biofilm form (P < 0.001). CONCLUSIONS: Coagulase-negative
      staphylococcus can be isolated from K-Pro surfaces despite the use of vancomycin
      prophylaxis. In this study, the majority of isolated strains had biofilm-forming
      capability. In vitro vancomycin tolerance assays suggest that biofilm formation
      decreases susceptibility to vancomycin. This may contribute to higher rates of
      infectious complications observed in these patients.

PMID- 26207307
TI  - The Association Between Menarche and Myopia: Findings From the Korean National
      Health and Nutrition Examination, 2008-2012.
AB  - PURPOSE: The purpose of this study was to analyze the relationship between age at
      menarche and myopia in Korean adult females. METHODS: A total of 8398 women of at
      least 19 years of age, who participated in the Korean National Health and
      Nutrition Examination Survey from 2008 to 2012, underwent a refractive
      examination using an autorefractor. The association between age at menarche and
      the severity of myopia was evaluated using a four-level multinomial logistic
      regression analysis. RESULTS: The prevalence of myopia was 61.77% (95% confidence
      interval [CI], 60.46-63.08), including 40.02% with low, 15.46% with moderate, and
      6.29% with high myopia. The mean age at menarche was 14.09 +/- 0.03 years. Age at
      menarche was inversely associated with the severity of myopia. In fully adjusted
      models, older age at menarche decreased the risk of moderate myopia (odds ratio
      [OR], 0.93; 95% CI, 0.86-0.99; P = 0.0261), and high myopia (OR, 0.85; 95% CI,
      0.77-0.95; P = 0.0012). CONCLUSIONS: Later age at menarche is associated with a
      decreased risk of moderate and high myopia. The effects of female sex hormones on
      ocular structures and growth spurts may mediate this relationship between age at
      menarche and myopia.

PMID- 26207308
TI  - Nationwide Incidence of Ocular Melanoma in South Korea by Using the National
      Cancer Registry Database (1999-2011).
AB  - PURPOSE: The purpose of this study was to determine the age-standardized
      incidence rate of ocular melanoma and its subtypes in South Korea from 1999 to
      2011. METHODS: The national cancer registry in South Korea was reviewed to
      ascertain all ocular melanoma incidents between 1999 and 2011, which covered the
      entire South Korean population. Age-standardized incidence rates of ocular
      melanoma and its subtypes were calculated. Trends in incidence were analyzed by
      the use of Joinpoint regression. Analyses were stratified by tumor type, sex,
      age, and year of cancer diagnosis. RESULTS: A total of 464 ocular melanoma cases
      (227 men [48.9%]) were identified from 1999 to 2011. The age-standardized
      incidence rate for 1999 to 2011 was 0.60 (95% confidence interval [CI]: 0.55
      0.66) per million people. Among ocular melanomas, uveal melanoma had the highest
      age-standardized incidence rate for 1999 to 2011 (0.42 [95% CI: 0.38-0.47] per
      million people), followed by conjunctival melanoma (0.12 [95% CI: 0.09-0.14] per
      million people). The age-standardized incidence rate was higher in 2006 to 2011
      than in 1999 to 2005, and increasing incidence trends were observed throughout
      the study period. CONCLUSIONS: Incidence rate of ocular melanoma for 1999 to 2011
      is relatively lower in South Korean population than in that reported in white
      population. Although ocular melanoma is still considered a rare cancer in South
      Korea, our findings suggest increasing incidence trends. This may warrant future
      in-depth study.

PMID- 26207309
TI  - Targeting Caspase-12 to Preserve Vision in Mice With Inherited Retinal
      Degeneration.
AB  - PURPOSE: The unfolded protein response is known to contribute to the inherited
      retinal pathology observed in T17M rhodopsin (T17M) mice. Recently it has been
      demonstrated that the endoplasmic reticulum stress-associated caspase-12 is
      activated during progression of retinal degeneration in different animal models.
      Therefore, we wanted to explore the role of caspase-12 in the mechanism of
      retinopathy in T17M mice and determine if inhibiting apoptosis in this way is a
      viable approach for halting retinal degeneration. METHODS: One, two-, and three
      month-old C57BL6/J, caspase-12-/-, T17M, and T17M caspase-12-/- mice were
      analyzed by scotopic ERG, spectral-domain optical coherence tomography (SD-OCT),
      histology, quantitative (q)RT-PCR, and Western blot of retinal RNA and protein
      extracts. Calpain and caspase-3/7 activity assays were measured in postnatal (P)
      day 30 retinal extracts. RESULTS: Caspase-12 ablation significantly prevented a
      decline in the a- and b-wave ERG amplitudes in T17M mice during three months,
      increasing the amplitudes from 232% to 212% and from 160% to 138%, respectively,
      as compared to T17M retinas. The SD-OCT results and photoreceptor row counts
      demonstrated preservation of retinal structural integrity and postponed
      photoreceptor cell death. The delay in photoreceptor cell death was due to
      significant decreases in the activity of caspase-3/7 and calpain, which
      correlated with an increase in calpastatin expression. CONCLUSIONS: We validated
      caspase-12 as a therapeutic target, ablation of which significantly protects T17M
      photoreceptors from deterioration. Although the inhibition of apoptotic activity
      alone was not sufficient to rescue T17M photoreceptors, in combination with other
      nonapoptotic targets, caspase-12 could be used to treat inherited retinopathy.

PMID- 26207310
TI  - Time Outdoors and Myopia Progression Over 2 Years in Chinese Children: The Anyang
      Childhood Eye Study.
AB  - PURPOSE: To investigate whether time outdoors and a range of other activities are
      associated with change in spherical equivalent (SE) and axial length in Chinese
      children over a period of 2 years. METHODS: A total of 1997 children aged 12.7 +/
      0.5 (10.9-15.6) years in the Anyang Childhood Eye Study (ACES) were examined
      annually (baseline and two follow-up visits). Myopia was defined as cycloplegic
      SE < -0.50 diopters (D). Questionnaires were administered to the students and
      parents at baseline to gauge time spent outdoors and on other tasks. We ran mixed
      linear models including age, sex, and years of follow-up. RESULTS: In the full
      cohort of children there was a suggestive association between time spent outdoors
      and change in axial length; however, the effect size was very small (high versus
      low tertile: -0.016 mm/y, P = 0.053). The association was observed in children
      not myopic at baseline (high versus low tertile, -0.036 mm/y; P = 0.009) but not
      in those already myopic at baseline (high versus low tertile: -0.005 mm/y; P =
      0.595). Time outdoors and change in SE showed similar, but nonsignificant,
      relationships (P > 0.05), perhaps due to insufficient statistical power. The
      other activities examined and parental myopia were not associated with changes in
      SE and axial length (P > 0.11). CONCLUSIONS: Within the normal range of variation
      encountered in these Chinese children, a wide range of activities were largely
      unrelated to myopia progression at this age. However, there was suggestive
      evidence that greater time outdoors was associated with slower axial elongation
      in nonmyopic teenagers, but not in existing myopes.

PMID- 26207311
TI  - The Influence of Oxygen on the Proliferative Capacity and Differentiation
      Potential of Lacrimal Gland-Derived Mesenchymal Stem Cells.
AB  - PURPOSE: The application of lacrimal gland-derived mesenchymal stem cells (LG
      MSC) for the regeneration of lacrimal gland tissue could result in a novel
      therapy for dry-eye syndrome. To optimize the culture conditions, the purpose of
      this study was to evaluate the influence of low oxygen on phenotype,
      differentiation potential, proliferative, and regenerative capacity of murine LG
      MSC. METHODS: Murine LG-MSC were cultured in 21% and 5% oxygen and characterized
      by flow cytometry, cell sorter assisted proliferation-, and colony forming unit
      assays. Reactive oxygen species (ROS) levels as well as lineage differentiation
      were evaluated. The effect of conditioned medium of LG-MSC from both oxygen
      conditions (CM MSC 21%, respectively, CM MSC 5%) on lacrimal gland epithelial
      cells (LG-EC) was examined in wound healing and proliferation assays. RESULTS:
      Cells under both culture conditions revealed differentiation potential and
      presented a MSC-specific flow cytometric phenotype. In 5% oxygen, cells yielded
      less ROS, showed a stable morphology, higher colony forming potential, and an
      increased proliferation capacity. Five percent oxygen significantly increased the
      number of CD44+ LG-MSC. Furthermore, CM MSC 5% significantly enhanced migration
      and proliferation in LG-EC. CONCLUSIONS: In vitro expansion in low oxygen
      preserves the proliferation capacity and differentiation potential of LG-MSC and
      increases the effects of conditioned medium on migration and proliferation in LG
      EC. Therefore, expansion in low oxygen seems to be an excellent method, to obtain
      vital MSC. Also, an increased number of LG-MSC expressing CD44 was observed under
      low oxygen, which might be a valuable marker to identify a potent MSC
      subpopulation.

PMID- 26207313
TI  - The Effect of Nonsense Mediated Decay on Transcriptional Activity Within the
      Novel beta-Thalassemia Mutation HBB: c.129delT.
AB  - Premature termination codons (PTCs) are caused by mutations in the coding
      sequences of functional genes resulting in an incorrect assignment of a stop
      codon. Abnormal and truncated proteins are prevented from being translated due to
      the rapid degradation of mRNA carrying these mutations by an RNA surveillance
      mechanism referred to as nonsense mediated decay (NMD). Recently, a novel
      mutation in a patient from Thailand with the clinical diagnosis of Hb E (HBB:
      c.79G > A)/beta(0)-thalassemia (Hb E/beta(0)-thal) and whose molecular analysis
      demonstrated a novel mutation in the beta-globin gene, HBB: c.129delT, was
      reported. The result of this deletion is a frameshift (FSC) resulting in a PTC at
      codon 60. We have analyzed the impact of this mutation on transcription and
      translation of the affected beta-globin gene using an in vitro model. The
      quantitative real-time polymerase chain reaction (qReTi-PCR) analysis revealed
      that this nucleotide mutation resulted in marked mRNA degradation, which we
      attributed to the NMD mechanism and as such, the expected deleterious truncated
      HBB was not generated. This result highlights a valuable application of our in
      vitro gene expression model that can be used to predict possible molecular
      pathology for any given nucleotide mutations. 

PMID- 26207312
TI  - Melatonin Entrains PER2::LUC Bioluminescence Circadian Rhythm in the Mouse
      Cornea.
AB  - PURPOSE: Previous studies have reported the presence of a circadian rhythm in
      PERIOD2::LUCIFERASE (PER2::LUC) bioluminescence in mouse photoreceptors, retina,
      RPE, and cornea. Melatonin (MLT) modulates many physiological functions in the
      eye and it is believed to be one of the key circadian signals within the eye. The
      aim of the present study was to investigate the regulation of the PER2::LUC
      circadian rhythm in mouse cornea and to determine the role played by MLT.
      METHODS: Corneas were obtained from PER2::LUC mice and cultured to measure
      bioluminescence rhythmicity in isolated tissue using a Lumicycle or CCD camera.
      To determine the time-dependent resetting of the corneal circadian clocks in
      response to MLT or IIK7 (a melatonin type 2 receptor, MT2, agonist) was added to
      the cultured corneas at different times of the day. We also defined the location
      of the MT2 receptor within different corneal layers using immunohistochemistry.
      RESULTS: A long-lasting bioluminescence rhythm was recorded from cultured
      PER2::LUC cornea and PER2::LUC signal was localized to the corneal epithelium and
      endothelium. MLT administration in the early night delayed the cornea rhythm,
      whereas administration of MLT at late night to early morning advanced the cornea
      rhythm. Treatment with IIK7 mimicked the MLT phase-shifting effect. Consistent
      with these results, MT2 immunoreactivity was localized to the corneal epithelium
      and endothelium. CONCLUSIONS: Our work demonstrates that MLT entrains the
      PER2::LUC bioluminescence rhythm in the cornea. Our data indicate that the cornea
      may represent a model to study the molecular mechanisms by which MLT affects the
      circadian clock.

PMID- 26207314
TI  - Incidence and Predictors of Bacterial infection in Febrile Children with Sickle
      Cell Disease.
AB  - Children with sickle cell disease are at increased risk of developing bacteremia
      and other serious bacterial infections. Fever is a common symptom in sickle cell
      disease and can also occur with sickle cell crises and viral infections. We aimed
      to evaluate the incidence and predictors of bacteremia and bacterial infection in
      children with sickle cell disease presenting with fever to a district hospital
      and sickle cell center in London. A retrospective analysis was performed on all
      attendances of children (aged under 16 years) with sickle cell disease presenting
      with a fever of 38.5  degrees C or higher over a 1-year period. Confirmed
      bacterial infection was defined as bacteremia, bacterial meningitis, urinary
      tract infection (UTI), pneumonia, osteomyelitis or other bacterial infection with
      positive identification of organism. Children were defined as having a suspected
      bacterial infection if a bacterial infection was suspected clinically, but no
      organism was identified. Over a 1-year period there were 88 episodes analyzed in
      59 children. Bacteremia occurred in 3.4% of episodes and confirmed bacterial
      infection in 7.0%. Suspected bacterial infection occurred in 33.0%. One death
      occurred from Salmonella typhirium septicemia. C-reactive protein (CRP) level and
      white blood cell (WBC) count were both significantly associated with bacterial
      infection (p = 0.004 and 0.02, respectively.) In conclusion, bacterial infections
      continue to be a significant problem in children with sickle cell disease. C
      reactive protein was significantly associated with bacterial infections, and
      could be included in clinical risk criteria for febrile children with sickle cell
      disease. 

PMID- 26207317
TI  - Content Themes of Alcohol Advertising in U.S. Television-Latent Class Analysis.
AB  - BACKGROUND: There is little alcohol research that reports on the thematic
      contents of contemporary alcohol advertisements in U.S. television. Studies of
      alcohol ads from 2 decades ago did not identify "Partying" as a social theme. Aim
      of this study was to describe and classify alcohol advertisements aired in
      national television in terms of contents, airing times, and channel placements
      and to identify different marketing strategies of alcohol brands. METHODS:
      Content analysis of all ads from the top 20 U.S. beer and spirit brands aired
      between July 2009 and June 2011. These were 581 unique alcohol ads accounting for
      272,828 (78%) national television airings. Ads were coded according to predefined
      definitions of 13 content areas. A latent class analysis (LCA) was conducted to
      define content cluster themes and determine alcoholic brands that were more
      likely to exploit these themes. RESULTS: About half of the advertisements (46%)
      were aired between 3 am and 8 pm, and the majority were placed either in
      Entertainment (40%) and Sports (38%) channels. Beer ads comprised 64% of the
      sample, with significant variation in airing times and channels between types of
      products and brands. LCA revealed 5 content classes that exploited the
      "Partying," "Quality," "Sports," "Manly," and "Relax" themes. The partying class,
      indicative of ad messages surrounding partying, love, and sex, was the dominant
      theme comprising 42% of all advertisements. Ads for alcopops, flavored spirits,
      and liqueur were more likely to belong to the party class, but there were also
      some beer brands (Corona, Heineken) where more than 67% of ads exploited this
      theme. CONCLUSIONS: This is the first analysis to identify a partying theme to
      contemporary alcohol advertising. Future analyses can now determine whether
      exposure to that or other themes predicts alcohol misuse among youth audiences.

PMID- 26207318
TI  - Genotypes of Ciprofloxacin-Resistant Klebsiella pneumoniae in Korea and Their
      Characteristics According to the Genetic Lineages.
AB  - We investigated the molecular genotypes of ciprofloxacin-resistant Klebsiella
      pneumoniae and their characteristics according to the genetic lineages. For 160
      K. pneumoniae collected in 2013, ciprofloxacin minimum inhibitory concentrations
      (MICs) were determined by agar dilution method. The genotypes of ciprofloxacin
      resistant K. pneumoniae isolates were determined by multilocus sequence typing
      (MLST) and wzi gene typing. The presence of plasmid-mediated resistance
      determinants [qnrA, qnrB, qnrS, aac(6')-Ib-cr, blaCTX-M, and blaSHV] was
      investigated. The gyrA and parC genes were sequenced. Fifty-seven isolates showed
      ciprofloxacin resistance. By MLST, four major sequence types (STs) or clonal
      complexes (CCs), that is, ST307, CC11, CC147, and ST15, were found and the two
      most prevalent STs were ST307 (14/57, 24.6%) and ST11 (12/57, 21.1%). By wzi gene
      sequencing, 46 of the 57 isolates could be differentiated. All the ST307 isolates
      had an identical wzi sequence and harbored qnrB. The majority of them harbored
      aac(6')-Ib-cr (85.7%) and CTX-M-15 (92.9%). In contrast, 12 ST11 isolates were
      divided into five sublineages by wzi sequence and qnrB, qnrS, and aac(6')-Ib-cr
      were carried by nine, seven, and three isolates, respectively. They harbored SHV
      type extended-spectrum beta-lactamase more frequently than CTX-M-15 (nine and
      four isolates, respectively). The prevalence of CTX-M-15, qnrB1, and aac(6')-Ib
      cr was significantly higher in ST307 than in ST11 (p=0.003, p=0.000, and p=0.002,
      respectively). Both clones had identical amino acid substitution in gyrA (S83I)
      and parC (S80I). K. pneumoniae ST307 and ST11 were the two most common clones,
      and the ST307 isolates were highly homogeneous, suggesting their recent
      emergence. 

PMID- 26207319
TI  - Letter to the Editor: Dynamic Cervical Implant.

PMID- 26207320
TI  - Assessment and classification of subsidence after lateral interbody fusion using
      serial computed tomography.
AB  - OBJECT Intervertebral cage settling during bone remodeling after lumbar lateral
      interbody fusion (LIF) is a common occurrence during the normal healing process.
      Progression of this settling with endplate collapse is defined as subsidence. The
      purposes of this study were to 1) assess the rate of subsidence after minimally
      invasive (MIS) LIF by CT, 2) distinguish between early cage subsidence (ECS) and
      delayed cage subsidence (DCS), 3) propose a descriptive method for classifying
      the types of subsidence, and 4) discuss techniques for mitigating the risk of
      subsidence after MIS LIF. METHODS A total of 128 consecutive patients (with 178
      treated levels in total) underwent MIS LIF performed by a single surgeon. The
      subsidence was deemed to be ECS if it was evident on postoperative Day 2 CT
      images and was therefore the result of an intraoperative vertebral endplate
      injury and deemed DCS if it was detected on subsequent CT scans (>= 6 months
      postoperatively). Endplate breaches were categorized as caudal (superior
      endplate) and/or cranial (inferior endplate), and as ipsilateral, contralateral,
      or bilateral with respect to the side of cage insertion. Subsidence seen in CT
      images (radiographic subsidence) was measured from the vertebral endplate to the
      caudal or cranial margin of the cage (in millimeters). Patient-reported outcome
      measures included visual analog scale, Oswestry Disability Index, and 36-Item
      Short Form Health Survey physical and mental component summary scores. RESULTS
      Four patients had ECS in a total of 4 levels. The radiographic subsidence (DCS)
      rates were 10% (13 of 128 patients) and 8% (14 of 178 levels), with 3% of
      patients (4 of 128) exhibiting clinical subsidence. In the DCS levels, 3 types of
      subsidence were evident on coronal and sagittal CT scans: Type 1, caudal
      contralateral, in 14% (2 of 14), Type 2, caudal bilateral with anterior cage
      tilt, in 64% (9 of 14), and Type 3, both endplates bilaterally, in 21% (3 of 14).
      The mean subsidence in the DCS levels was 3.2 mm. There was no significant
      difference between the numbers of patients in the subsidence (DCS) and no
      subsidence groups who received clinical benefit from the surgical procedure,
      based on the minimum clinically important difference (p > 0.05). There was a
      significant difference between the fusion rates at 6 months (p = 0.0195);
      however, by 12 months, the difference was not significant (p = 0.2049).
      CONCLUSIONS The authors distinguished between ECS and DCS. Radiographic
      subsidence (DCS) was categorized using descriptors for the location and severity
      of the subsidence. Neither interbody fusion rates nor clinical outcomes were
      affected by radiographic subsidence. To protect patients from subsidence after
      MIS LIF, the surgeon needs to take care with the caudal endplate during cage
      insertion. If a caudal bilateral (Type 2) endplate breach is detected,
      supplemental posterior fixation to arrest progression and facilitate fusion is
      recommended.

PMID- 26207322
TI  - A systematic review of the public's knowledge and understanding of Alzheimer's
      disease and dementia.
AB  - This paper reports findings from a systematic review of the literature on the
      general public's knowledge and understanding of dementia/Alzheimer's disease. The
      key purpose of the review was to evaluate existing literature with specific
      attention paid to conceptual and methodological issues and to key findings. Over
      a 20-year period, 40 published articles satisfied the inclusion criteria. Only 4
      of these were qualitative and 5 were cross-national. The review revealed a lack
      of consistency across studies regarding how knowledge was operationalized,
      approaches to sampling, response rates, and data collection instruments used
      including validated scales. A consistent finding across the vast majority of
      studies was the only fair to moderate knowledge and understanding the general
      public had. The most common misconception was that dementia was a normal part of
      aging and there was a lack of clarity about at which point normal age-related
      memory loss problems become severe enough to indicate dementia. Knowledge of
      dementia was found to be particularly poor among racial and ethnic minority
      groups where several myths about causes of dementia were found. Findings point to
      the need for more educational and advocacy programmes on dementia to be developed
      particularly in low-income to middle-income countries. 

PMID- 26207323
TI  - Role of Cholestyramine in Refractory Hyperthyroidism: A Case Report and
      Literature Review.
AB  - BACKGROUND: Hyperthyroidism is a common disease that usually responds to the
      conventional therapy of anti-thyroidal medications (methimazole or PTU) and beta
      blocker. Refractory hyperthyroidism is a rare condition in which hyperthyroidism
      fails to respond to the above therapy. Cholestyramine has been shown to decrease
      thyroid hormone level when added to the ongoing anti-thyroidal medications. CASE
      REPORT: A 52-year-old woman with past medical history of enlarging goiter
      presented with obstructive symptoms of worsening shortness of breath and snoring.
      Admission thyroid function test showed mild hyperthyroidism (suppressed TSH,
      slightly high FT4, and high normal FT3) that worsened after she received a CT
      scan with contrast and failed to respond to a 3-week course of high-dose
      dexamethasone, high-dose carbimazole, and up-titrated propranolol. Five days
      after cholestyramine was added, her FT4 decreased by 30% and normalized after 12
      days. The patient underwent total thyroidectomy as definitive treatment for the
      hyperthyroidism and for the obstructive symptoms. CONCLUSIONS: Cholestyramine is
      an effective additional treatment for hyperthyroidism and may be an effective
      treatment for refractory iodine-induced hyperthyroidism. The possibility of self
      remission (natural course) is less likely given the dramatic and rapid response
      to cholestyramine.

PMID- 26207321
TI  - Development and validation of a UPLC-MS/MS method for the determination of
      cucurbitacin B in rat plasma and application to a pharmacokinetic study.
AB  - Cucurbitacin B (CuB), one of the most abundant forms of cucurbitacins, is a
      promising natural anticancer drug candidate. Although the anticancer activity of
      CuB has been well demonstrated, information regarding the pharmacokinetics is
      limited. A rapid, selective and sensitive UPLC-MS/MS for CuB was developed and
      validated using hemslecin A (HeA) as internal standard (IS). Plasma samples were
      pre-treated by liquid-liquid extraction with dichloromethane. Separation was
      achieved on a reversed-phase C18 column (50 * 4.6 mm, 5 um) at 35 degrees C using
      isocratic elution with water-methanol (25:75, v/v) at a flow rate of 0.3 mL/min.
      The analytes were monitored by a triple quadrupole tandem mass spectrometer with
      positive electrospray ionization mode. The calibration curve was linear (r >
      0.995) in a concentration range of 0.3-100 ng/mL with a limit of quantification
      of 0.3 ng/mL. Intra- and inter-day accuracy and precision were validated by
      percentage relative error and relative standard deviation, respectively, which
      were both lower than the limit of 15%. This assay was successfully applied to a
      pharmacokinetic study of CuB in Wistar rats.

PMID- 26207324
TI  - Colossal Ultraviolet Photoresponsivity of Few-Layer Black Phosphorus.
AB  - Black phosphorus has an orthorhombic layered structure with a layer-dependent
      direct band gap from monolayer to bulk, making this material an emerging material
      for photodetection. Inspired by this and the recent excitement over this
      material, we studied the optoelectronics characteristics of high-quality, few
      layer black phosphorus-based photodetectors over a wide spectrum ranging from
      near-ultraviolet (UV) to near-infrared (NIR). It is demonstrated for the first
      time that black phosphorus can be configured as an excellent UV photodetector
      with a specific detectivity ~3 * 10(13) Jones. More critically, we found that the
      UV photoresponsivity can be significantly enhanced to ~9 * 10(4) A W(-1) by
      applying a source-drain bias (VSD) of 3 V, which is the highest ever measured in
      any 2D material and 10(7) times higher than the previously reported value for
      black phosphorus. We attribute such a colossal UV photoresponsivity to the
      resonant-interband transition between two specially nested valence and conduction
      bands. These nested bands provide an unusually high density of states for highly
      efficient UV absorption due to the singularity of their nature. 

PMID- 26207325
TI  - Thermoresponsive Nanoparticles of Self-Assembled Block Copolymers as Potential
      Carriers for Drug Delivery and Diagnostics.
AB  - Thermally responsive hydrogel nanoparticles composed of self-assembled
      polystyrene-b-poly(N-isopropylacrylamide)-b-polystyrene block copolymers and
      fluorescent probe 1-anilinonaphthalene-8-sulfonic acid have been prepared by
      aerosol flow reactor method. We aimed exploring the relationship of intraparticle
      morphologies, that were, PS spheres and gyroids embedded in PNIPAm matrix, as
      well PS-PNIPAm lamellar structure, to probe release in aqueous solution below and
      above the cloud point temperature (CPT) of PNIPAm. The release was detected by
      fluorescence emission given by the probe binding to bovine serum albumin. Also,
      the colloidal behavior of hydrogel nanoparticles at varying temperatures were
      examined by scattering method. The probe release was faster below than above the
      CPT from all the morphologies of which gyroidal morphology showed the highest
      release. Colloidal behavior varied from single to moderately aggregated particles
      in order spheres-gyroids-lamellar. Hydrogel nanoparticles with tunable intra
      particle self-assembled morphologies can be utilized designing carrier systems
      for drug delivery and diagnostics. 

PMID- 26207327
TI  - Enhancement of 4-electron O2 reduction by a Cu(ii)-pyridylamine complex via
      protonation of a pendant pyridine in the second coordination sphere in water.
AB  - We have synthesised a novel copper(ii) complex with a pyridine pendant as a
      proton relay port for electrocatalytic 4e(-) reduction of O2 in water. The
      enhancement of the electrocatalytic O2 reduction via protonation of the pyridine
      pendant is demonstrated in comparison with a copper(ii) complex without the
      pyridine pendant. 

PMID- 26207329
TI  - Challenges, Progresses, and Promises for Developing Future NADPH Oxidase
      Therapeutics.
AB  - NADPH oxidase (NOX) enzymes show great potential as therapeutic pharmacological
      targets. This Forum revolves around the roles of specific NOX isoforms in
      oxidative stress-mediated pathologies, available NOX antagonists/agonists as well
      as the potential side effects of NOX inhibition and the requisite identification
      of novel oxidative biomarkers as a measure of NOX activity in patients. In
      addition, an original article reports the discovery of a novel small molecule
      NOX2 inhibitor. Finally an attractive and innovative therapeutic approach for
      modulating NOX activity through the inhibition of the proton channel Hv1 is
      discussed.

PMID- 26207328
TI  - Exceedingly Concise and Elegant Synthesis of (+)-Paniculatine, (-)-Magellanine,
      and (+)-Magellaninone.
AB  - Starting from inexpensive (+)-pulegone as the chiral building block, a highly
      convergent synthesis of the unusual diquinane-based structures of (+)
      paniculatine (1), (-)-magellanine (2), and (+)-magellaninone (3), has been
      achieved. This approach is based upon a tandem acylation-alkylation of ketoester
      8 and palladium-catalyzed olefin insertion, oxidation, and hydrogenation for
      construction of the tetracyclic framework. This exceedingly concise strategy,
      requiring only 12-14 steps, is the shortest to date. 

PMID- 26207330
TI  - Communications to children about mental illness and their role in stigma
      development: an integrative review.
AB  - BACKGROUND: Limited literature on the stigma of mental illness has examined the
      socio-cultural processes involved in the development of stigma around mental
      health in children, which emerges in mid-childhood (7-11 years). Greater
      understanding might inform preventative interventions. AIMS: This review aims to
      integrate disparate theoretical and empirical research to provide an overview of
      social communications to children aged 7--11 years about mental illness and their
      role in the development of stigmatised views. Four key socio-cultural contexts
      (the media, school, peers, parents) of relevance to children's development will
      be considered. METHOD: Systematic literature searches were conducted within
      electronic databases and abstracts were scanned to identify relevant studies.
      Fifteen papers were selected for the review. RESULTS: The review found few
      studies have directly examined communications about mental illness to children.
      Available evidence suggests messages across children's socio-cultural contexts
      are characterised by silence and stigma, which may shape children's developing
      views. Specific theoretical frameworks are lacking; possible mechanisms of
      transmission are discussed. CONCLUSIONS: This review suggests overcoming stigma
      will require efforts targeting young children, explicitly tackling mental
      illness, and spanning multiple social spheres: further research is warranted.

PMID- 26207332
TI  - ?

PMID- 26207331
TI  - How do people learn from negative evidence? Non-monotonic generalizations and
      sampling assumptions in inductive reasoning.
AB  - A robust finding in category-based induction tasks is for positive observations
      to raise the willingness to generalize to other categories while negative
      observations lower the willingness to generalize. This pattern is referred to as
      monotonic generalization. Across three experiments we find systematic non
      monotonicity effects, in which negative observations raise the willingness to
      generalize. Experiments 1 and 2 show that this effect emerges in hierarchically
      structured domains when a negative observation from a different category is added
      to a positive observation. They also demonstrate that this is related to a
      specific kind of shift in the reasoner's hypothesis space. Experiment 3 shows
      that the effect depends on the assumptions that the reasoner makes about how
      inductive arguments are constructed. Non-monotonic reasoning occurs when people
      believe the facts were put together by a helpful communicator, but monotonicity
      is restored when they believe the observations were sampled randomly from the
      environment.

PMID- 26207333
TI  - ?

PMID- 26207335
TI  - ?

PMID- 26207334
TI  - ?

PMID- 26207336
TI  - ?

PMID- 26207338
TI  - In vitro rumen fermentation and digestibility of buffaloes as influenced by grape
      pomace powder and urea treated rice straw supplementation.
AB  - This study aimed to investigate the effect of grape pomace powder levels and
      roughage sources on gas kinetics, digestibility and fermentation of swamp
      buffaloes by using in vitro techniques. The experimental design was a 2 * 4
      factorial arrangement in a completely randomized design. Factor A was two sources
      of roughage (untreated rice straw, RS, and 3% urea treated rice straw, UTRS) and
      factor B was four levels of grape pomace powder (GPP) supplementation (0, 2, 4,
      6% of substrate) on a dry matter basis. Results revealed that GPP supplementation
      at 2, 4 and 6% of substrate influenced gas kinetics. Cumulative gas production
      tended to be lower in the supplemented group. In vitro true digestibility was
      higher in the GPP supplementation at 2% with UTRS while microbial mass was higher
      in the supplemented groups. Supplementation of GPP significantly increased the
      total volatile fatty acids, especially propionate. Calculated methane production
      was subsequently decreased in the supplemented groups. Bacterial population was
      higher while protozoal population was lower by GPP supplementation. It could be
      concluded that supplementation of GPP at 2% of the substrate with UTRS improved
      in vitro true digestibility, rumen fermentation end-products as well as reducing
      methane production. 

PMID- 26207337
TI  - Major Histocompatibility Complex Class II Dextramers: New Tools for the Detection
      of antigen-Specific, CD4 T Cells in Basic and Clinical Research.
AB  - The advent of major histocompatibility complex (MHC) tetramer technology has been
      a major contribution to T cell immunology, because tetramer reagents permit
      detection of antigen-specific T cells at the single-cell level in heterogeneous
      populations by flow cytometry. However, unlike MHC class I tetramers, the utility
      of MHC class II tetramers has been less frequently reported. MHC class II
      tetramers can be used successfully to enumerate the frequencies of antigen
      specific CD4 T cells in cells activated in vitro, but their use for ex vivo
      analyses continues to be a problem, due in part to their activation dependency
      for binding with T cells. To circumvent this problem, we recently reported the
      creation of a new generation of reagents called MHC class II dextramers, which
      were found to be superior to their counterparts. In this review, we discuss the
      utility of class II dextramers vis-a-vis tetramers, with respect to their
      specificity and sensitivity, including potential applications and limitations.

PMID- 26207339
TI  - Deubiquitinase inhibition by WP1130 leads to ULK1 aggregation and blockade of
      autophagy.
AB  - Autophagy represents an intracellular degradation process which is involved in
      both regular cell homeostasis and disease settings. In recent years, the
      molecular machinery governing this process has been elucidated. The ULK1 kinase
      complex consisting of the serine/threonine protein kinase ULK1 and the adapter
      proteins ATG13, RB1CC1, and ATG101, is centrally involved in the regulation of
      autophagy initiation. This complex is in turn regulated by the activity of
      different nutrient- or energy-sensing kinases, including MTOR, AMPK, and AKT.
      However, next to phosphorylation processes it has been suggested that
      ubiquitination of ULK1 positively influences ULK1 function. Here we report that
      the inhibition of deubiquitinases by the compound WP1130 leads to increased ULK1
      ubiquitination, the transfer of ULK1 to aggresomes, and the inhibition of ULK1
      activity. Additionally, WP1130 can block the autophagic flux. Thus, treatment
      with WP1130 might represent an efficient tool to inhibit the autophagy-initiating
      ULK1 complex and autophagy. 

PMID- 26207340
TI  - A high-performance imaging probe with NIR luminescence and synergistically
      enhanced T1-T2 relaxivity for in vivo hepatic tumor targeting and multimodal
      imaging.
AB  - A high-performance imaging probe with NIR luminescence and synergistically
      enhanced T1-T2 relaxivity was synthesized. This nanoprobe exhibits a relatively
      high tumor-targeting efficacy and enables NIR optical and T1-/T2-weighted MR
      imaging of hepatic tumor cells in vivo. 

PMID- 26207342
TI  - Structural and reactivity models for copper oxygenases: cooperative effects and
      novel reactivities.
AB  - Dioxygen is widely used in nature as oxidant. Nature itself has served as
      inspiration to use O2 in chemical synthesis. However, the use of dioxygen as an
      oxidant is not straightforward. Its triplet ground-state electronic structure
      makes it unreactive toward most organic substrates. In natural systems,
      metalloenzymes activate O2 by reducing it to more reactive peroxide (O2(2-)) or
      superoxide (O2(-)) forms. Over the years, the development of model systems
      containing transition metals has become a convenient tool for unravelling O2
      activation mechanistic aspects and reproducing the oxidative activity of enzymes.
      Several copper-based systems have been developed within this area. Tyrosinase is
      a copper-based O2-activating enzyme, whose structure and reactivity have been
      widely studied, and that serves as a paradigm for O2 activation at a dimetal
      site. It contains a dicopper center in its active site, and it catalyzes the
      regioselective ortho-hydroxylation of phenols to catechols and further oxidation
      to quinones. This represents an important step in melanin biosynthesis and it is
      mediated by a dicopper(II) side-on peroxo intermediate species. In the present
      accounts, our research in the field of copper models for oxygen activation is
      collected. We have developed m-xylyl linked dicopper systems that mimick
      structural and reactivity aspects of tyrosinase. Synergistic cooperation of the
      two copper(I) centers results in O2 binding and formation of bis(MU
      oxo)dicopper(III) cores. These in turn bind and ortho-hydroxylate phenolates via
      an electrophilic attack of the oxo ligand over the arene. Interestingly the
      bis(MU-oxo)dicopper(III) cores can also engage in ortho-hydroxylation
      defluorination of deprotonated 2-fluorophenols, substrates that are well-known
      enzyme inhibitors. Analysis of Cu2O2 species with different binding modes show
      that only the bis(MU-oxo)dicopper(III) cores can mediate the reaction. Finally,
      the use of unsymmetric systems for oxygen activation is a field that still
      remains rather unexplored. We envision that the unsymmetry might infere
      interesting new reactivities. We contributed to this topic with the development
      of an unsymmetric ligand (m-XYL(N3N4)), whose dicuprous complex reacts with O2
      and forms a trans-peroxo dicopper(II) species that showed a markedly different
      reactivity compared to a symmetric trans-peroxo dicopper(II) analog. Nucleophilic
      reactivity is observed for the unsymmetric trans-peroxo dicopper(II) species
      against electrophilies such as H(+), CO2 and aldehydes, and neither oxygen atom
      transfer nor hydrogen abstraction is observed when reacting with oxygen atom
      acceptors (triphenyl phosphine, sulfides) and substrates with weak C-H bonds.
      Instead, electrophilic monooxygenase-like ortho-hydroxylation reactivity is
      described for these unsymmetric species upon reaction with phenolates. Finally,
      by using a second dinucleating unsymmetric ligand (L(N3N4)), we have described
      copper(I) containing heterodimetallic systems and explored their O2 binding
      properties. Site specific metalation led to the generation of dimeric
      heterometallic M'CuO2CuM' species from intermolecular O2 binding at copper sites.

PMID- 26207341
TI  - Three SAUR proteins SAUR76, SAUR77 and SAUR78 promote plant growth in
      Arabidopsis.
AB  - Ethylene perceived by a family of five receptors regulates many developmental
      processes in Arabidopsis. Here we conducted the yeast two-hybrid assay to screen
      for additional unidentified proteins that interact with subfamily II ethylene
      receptor ETR2. Three SAUR proteins, named SAUR76, 77 and 78, were identified to
      associate with both ETR2 and EIN4 in different assays. Interaction of SAUR76 and
      SAUR78 with ETR2 was further verified by co-immunoprecipitation and bimolecular
      fluorescence complementation (BiFC) assays. Expressions of SAUR76-78 are induced
      by auxin and ethylene treatments. Compared with wild type, SAUR-overexpressing
      plants exhibit reduced ethylene sensitivity, while SAUR-RNAi lines exhibit
      enhanced ethylene sensitivity. Overexpressing the three SAURs partially
      complements the phenotype of subfamily II ethylene receptor loss-of-function
      double mutant etr2-3ein4-4, which has increased ethylene response and small
      cotyledon and rosette. saur76 mutation partially suppresses the reduced ethylene
      sensitivity of etr2-2. SAUR76/78 proteins are regulated by 26S proteasome system
      and larger tag increases their protein stability. These findings suggest that
      SAUR76-78 may affect ethylene receptor signaling and promote plant growth in
      Arabidopsis. 

PMID- 26207343
TI  - Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum
      Retained Mutants.
AB  - Prohormone convertase 1/3 (PC1/3), encoded by the gene PCSK1, is critical for
      peptide hormone synthesis. An increasing number of studies have shown that
      inactivating mutations in PCSK1 are correlated with endocrine pathologies ranging
      from intestinal dysfunction to morbid obesity, whereas the common nonsynonymous
      polymorphisms rs6232 (N221D) and rs6234-rs6235 (Q665E-S690T) are highly
      associated with obesity risk. In this report, we revisited the biochemical and
      cellular properties of PC1/3 variants in the context of a wild-type PC1/3
      background instead of the S357G hypermorph background used for all previous
      studies. In the wild-type background the PC1/3 N221D variant exhibited 30% lower
      enzymatic activity in a fluorogenic assay than wild-type PC1/3; this inhibition
      was greater than that detected in an equivalent experiment using the PC1/3 S357G
      background. A PC1/3 variant with the linked carboxyl-terminal polymorphisms Q665E
      S690T did not show this difference. We also analyzed the biochemical properties
      of 2 PC1/3 mutants, G209R and G593R, which are retained in the endoplasmic
      reticulum (ER), and studied their effects on wild-type PC1/3. The expression of
      ER-retained mutants induced ER stress markers and also resulted in dominant
      negative blockade of wild-type PC1/3 prodomain cleavage and decreased expression
      of wild-type PC1/3, suggesting facilitation of the entry of wild-type protein to
      a degradative proteasomal pathway. Dominant-negative effects of PC1/3 mutations
      on the expression and maturation of wild-type protein, with consequential effects
      on PC1/3 availability, add a new element which must be considered in population
      and clinical studies of this gene. 

PMID- 26207344
TI  - Adrenal Steroid Metabolites Accumulating in Congenital Adrenal Hyperplasia Lead
      to Transactivation of the Glucocorticoid Receptor.
AB  - Patients with congenital adrenal hyperplasia (CAH) are often clinically less
      severely affected by cortisol deficiency than anticipated from their enzymatic
      defect. We hypothesize that adrenal steroid hormone precursors that accumulate in
      untreated or poorly controlled CAH have glucocorticoid activity and partially
      compensate for cortisol deficiency. We studied the in vitro effects of 17
      hydroxyprogesterone (17OHP), progesterone (P), 21-deoxycortisol (21DF), and
      androstenedione (Delta4) on the human glucocorticoid receptor (hGR). Competitive
      binding assays were performed in HeLa cells. Nuclear translocation of the hGR was
      studied by transfection of COS-7 cells with a GFP-tagged hGR and fluorescence
      microscopy. Transactivation assays were performed in COS-7 cells and in HEK 293
      cells after cotransfection with hGR and luciferase reporter vectors using a dual
      luciferase assay. 17OHP, P, and 21DF are able to bind to the hGR with binding
      affinities of 24-43% compared with cortisol. Delta4 has a low binding affinity.
      Incubation with 21DF led to complete nuclear translocation of the hGR, whereas
      treatment with 17OHP or P resulted in partial nuclear translocation. 21DF
      transactivated the hGR with an EC50 approximately 6 times the EC50 of cortisol.
      17OHP and P transactivated the hGR with EC50s of more than 100 times the EC50 of
      cortisol. No hGR transactivation was detected after incubation with Delta4. 21DF,
      17OHP, and P are able to bind, translocate, and transactivate the hGR in vitro
      and thus may have glucocorticoid activity. 21DF might have a clinically relevant
      agonistic effect on the hGR and could potentially partially compensate the
      cortisol deficiency in CAH patients. 

PMID- 26207345
TI  - Fsh Stimulates Spermatogonial Proliferation and Differentiation in Zebrafish via
      Igf3.
AB  - Growth factors modulate germ line stem cell self-renewal and differentiation
      behavior. We investigate the effects of Igf3, a fish-specific member of the igf
      family. Fsh increased in a steroid-independent manner the number and mitotic
      index of single type A undifferentiated spermatogonia and of clones of type A
      differentiating spermatogonia in adult zebrafish testis. All 4 igf gene family
      members in zebrafish are expressed in the testis but in tissue culture only igf3
      transcript levels increased in response to recombinant zebrafish Fsh. This
      occurred in a cAMP/protein kinase A-dependent manner, in line with the results of
      studies on the igf3 gene promoter. Igf3 protein was detected in Sertoli cells.
      Recombinant zebrafish Igf3 increased the mitotic index of type A undifferentiated
      and type A differentiating spermatogonia and up-regulated the expression of genes
      related to spermatogonial differentiation and entry into meiosis, but Igf3 did
      not modulate testicular androgen release. An Igf receptor inhibitor blocked these
      effects of Igf3. Importantly, the Igf receptor inhibitor also blocked Fsh-induced
      spermatogonial proliferation. We conclude that Fsh stimulated Sertoli cell
      production of Igf3, which promoted via Igf receptor signaling spermatogonial
      proliferation and differentiation and their entry into meiosis. Because previous
      work showed that Fsh also released spermatogonia from an inhibitory signal by
      down-regulating anti-Mullerian hormone and by stimulating androgen production, we
      can now present a model, in which Fsh orchestrates the activity of stimulatory
      (Igf3, androgens) and inhibitory (anti-Mullerian hormone) signals to promote
      spermatogenesis. 

PMID- 26207346
TI  - The Effect of an Oxytocin Receptor Antagonist (Retosiban, GSK221149A) on the
      Response of Human Myometrial Explants to Prolonged Mechanical Stretch.
AB  - Multiple pregnancy is a major cause of spontaneous preterm birth, which is
      related to uterine overdistention. The objective of this study was to determine
      whether an oxytocin receptor antagonist, retosiban (GSK221149A), inhibited the
      procontractile effect of stretch on human myometrium. Myometrial biopsies were
      obtained at term planned cesarean delivery (n = 12). Each biopsy specimen was
      dissected into 8 strips that were exposed in pairs to low or high stretch (0.6 or
      2.4 g) in the presence of retosiban (1 MUM) or vehicle (dimethylsulfoxide) for 24
      hours. Subsequently, we analyzed the contractile responses to KCl and oxytocin in
      the absence of retosiban. We found that incubation under high stretch in vehicle
      alone increased the response of myometrial explants to both KCl (P = .007) and
      oxytocin (P = .01). However, there was no statistically significant effect of
      stretch when explants were incubated with retosiban (P = .3 and .2,
      respectively). Incubation with retosiban in low stretch had no statistically
      significant effect on the response to either KCl or oxytocin (P = .8 and >.9,
      respectively). Incubation with retosiban in high stretch resulted in a
      statistically significant reduction (median fold change, interquartile range, P)
      in the response to both KCl (0.74, 0.60-1.03, P = .046) and oxytocin (0.71, 0.53
      0.91, P = .008). The greater the effect of stretch on explants from a given
      patient, the greater was the inhibitory effect of retosiban (r = -0.65, P = .02
      for KCl and r= -0.73, P = .007 for oxytocin). These results suggest that
      retosiban prevented stretch-induced stimulation of human myometrial
      contractility. Retosiban treatment is a potential approach for preventing preterm
      birth in multiple pregnancy. 

PMID- 26207348
TI  - The effect of temperament on the treatment adherence of bipolar disorder type I.
AB  - BACKGROUND AND AIMS: Treatment adherence is one of the most important factors
      that may determine treatment response in patients with bipolar disorders (BD).
      Many factors have been described to be associated with treatment adherence in BD.
      Temperament that can influence the course of BD will have an impact on treatment
      adherence. The aim of this study is to investigate temperament effect on
      treatment adherence in euthymic patients with BD-I. METHODS: Eighty patients with
      BD-I participated in the study. A psychiatrist used the Structured Clinical
      Interview for DSM-IV Axis-I Disorders to determine the diagnosis and co
      morbidities. Hamilton Depression and Young Mania Rating Scale were used to detect
      the remission. We used the Temperament Evaluation of Memphis, Pisa, Paris, San
      Diego Autoquestionnaire and the 4-item Morisky Medication Adherence Scale to
      evaluate temperament and treatment adherence, respectively. The study group was
      divided into two groups as "treatment adherent" and "treatment non-adherent".
      RESULTS: The cyclothymic and anxious temperament scores of the treatment non
      adherent patients with BD-I were significantly higher than those of the treatment
      adherent group (p < 0.001, p = 0.006, respectively). Multiple linear regression
      analysis determined that cyclothymic temperament predicted treatment non
      adherence (p = 0.009). CONCLUSION: It should be kept in mind that BD-I patients
      with cyclothymic temperament may be treatment non-adherent and future studies
      should explore whether temperament characteristics deteriorate BD-I course by
      disrupting treatment adherence.

PMID- 26207350
TI  - Synthesis of cobalt cluster-based supramolecular triple-stranded helicates.
AB  - A cobalt cluster-based triple-stranded helicate, Co8(PDA)6(PTA)3(DMF)3(H2O)3 ()
      (PDA = 2,6-pyridinedicarboxylate, PTA = benzene-1,3-dicarboxylate, DMF =
      dimethylformamide) was successfully synthesized and fully characterized. Complex
      can be used as a supramolecular building block in constructing a higher-order
      helix-of-helix structure, [Co8(PDA)6(PTA)3(DMF)2(H2O)4-0.51(Co(OHn)2)] (n = 1 or
      2) (). 

PMID- 26207349
TI  - Long-term sustained disease control in patients with mantle cell lymphoma with or
      without active disease after treatment with allogeneic hematopoietic cell
      transplantation after nonmyeloablative conditioning.
AB  - BACKGROUND: Previously, early results were reported for allogeneic hematopoietic
      cell transplantation (HCT) after nonmyeloablative conditioning with 2 Gy of total
      body irradiation with or without fludarabine and/or rituximab in 33 patients with
      mantle cell lymphoma (MCL). METHODS: This study examined the outcomes of 70
      patients with MCL and included extended follow-up (median, 10 years) for the 33
      initial patients. Grafts were obtained from human leukocyte antigen (HLA)
      matched, related donors (47%), unrelated donors (41%), and HLA antigen-mismatched
      donors (11%). RESULTS: The 5-year incidence of nonrelapse mortality was 28%. The
      relapse rate was 26%. The 5-year rates of overall survival (OS) and progression
      free survival (PFS) were 55% and 46%, respectively. The 10-year rates of OS and
      PFS were 44% and 41%, respectively. Eighty percent of surviving patients were off
      immunosuppression at the last follow-up. The presence of relapsed or refractory
      disease at the time of HCT predicted a higher rate of relapse (hazard ratio [HR],
      2.94; P = .05). Despite this, OS rates at 5 (51% vs 58%) and 10 years (43% vs
      45%) were comparable between those with relapsed/refractory disease and those
      undergoing transplantation with partial or complete remission. A high-risk
      cytomegalovirus (CMV) status was the only independent predictor of worse OS (HR,
      2.32; P = .02). A high-risk CMV status and a low CD3 dose predicted PFS (HR,
      2.22; P = .03). CONCLUSIONS: Nonmyeloablative allogeneic HCT provides a long-term
      survival benefit for patients with relapsed MCL, including those with refractory
      disease or multiple relapses.

PMID- 26207351
TI  - The transformative meanings of viewing or not viewing the body after sudden
      death.
AB  - This study investigates the experience of viewing or not viewing the body for 64
      relatives bereaved after a sudden and unexpected death. (1) (1)Mowll (2011).
      Transition to a new reality: the experience of viewing or not viewing the body of
      a relative in the context of grief after a sudden and unexpected death.
      University of New South Wales, Social Sciences & International Studies
      http://primoa.library.unsw.edu.au/UNSWS:TN_trovehttp_//handle.unsw.edu.au/1959.4/
      1303 Thematic analyses of in-depth interviews reveal the importance of viewing
      and the challenges in providing choice. Some participants experienced
      difficulties including regret and intrusive images. These are discussed alongside
      the transformative meanings of seeing or not seeing the body for bereaved
      relatives. 

PMID- 26207352
TI  - 14-3-3zeta deficient mice in the BALB/c background display behavioural and
      anatomical defects associated with neurodevelopmental disorders.
AB  - Sequencing and expression analyses implicate 14-3-3zeta as a genetic risk factor
      for neurodevelopmental disorders such as schizophrenia and autism. In support of
      this notion, we recently found that 14-3-3zeta(-/-) mice in the Sv/129 background
      display schizophrenia-like defects. As epistatic interactions play a significant
      role in disease pathogenesis we generated a new congenic strain in the BALB/c
      background to determine the impact of genetic interactions on the 14-3-3zeta(-/-)
      phenotype. In addition to replicating defects such as aberrant mossy fibre
      connectivity and impaired spatial memory, our analysis of 14-3-3zeta(-/-) BALB/c
      mice identified enlarged lateral ventricles, reduced synaptic density and
      ectopically positioned pyramidal neurons in all subfields of the hippocampus. In
      contrast to our previous analyses, 14-3-3zeta(-/-) BALB/c mice lacked locomotor
      hyperactivity that was underscored by normal levels of the dopamine transporter
      (DAT) and dopamine signalling. Taken together, our results demonstrate that
      dysfunction of 14-3-3zeta gives rise to many of the pathological hallmarks
      associated with the human condition. 14-3-3zeta-deficient BALB/c mice therefore
      provide a novel model to address the underlying biology of structural defects
      affecting the hippocampus and ventricle, and cognitive defects such as
      hippocampal-dependent learning and memory. 

PMID- 26207353
TI  - Social network bridging potential and the use of complementary and alternative
      medicine in later life.
AB  - The use of complementary/alternative medicine (CAM) is typically modeled as a
      function of individual health beliefs, including changes in perceptions of
      conventional medicine, an orientation toward more holistic care, and increasing
      patient involvement in health care decision-making. Expanding on research that
      shows that health-related behavior is shaped by social networks, this paper
      examines the possibility that CAM usage is partly a function of individuals'
      social network structure. We argue that people are more likely to adopt CAM when
      they function as bridges between network members who are otherwise not (or
      poorly) connected to each other. This circumstance not only provides individuals
      with access to a wider range of information about treatment options, it also
      reduces the risk of sanctioning by network members if one deviates from
      conventional forms of treatment. We test this idea using data from the National
      Social Life, Health, and Aging Project (NSHAP), a nationally representative study
      of older Americans. Analyses of egocentric social network data show that older
      adults with bridging potential in their networks are significantly more likely to
      engage in a greater number of types of CAM. We close by discussing alternative
      explanations of these findings and their potential implications for research on
      CAM usage. 

PMID- 26207354
TI  - Surface-to-volume ratio mapping of tumor microstructure using oscillating
      gradient diffusion weighted imaging.
AB  - PURPOSE: To disentangle the free diffusivity (D0 ) and cellular membrane
      restrictions, by means of their surface-to-volume ratio (S/V), using the
      frequency-dependence of the diffusion coefficient D(omega), measured in brain
      tumors in the short diffusion-time regime using oscillating gradients (OGSE).
      METHODS: In vivo and ex vivo OGSE experiments were performed on mice bearing the
      GL261 murine glioma model (n = 10) to identify the relevant time/frequency
      (t/omega) domain where D(omega) linearly decreases with omega(-1/2) . Parametric
      maps (S/V, D0 ) are compared with conventional DWI metrics. The impact of
      frequency range and temperature (20 degrees C versus 37 degrees C) on S/V and D0
      is investigated ex vivo. RESULTS: The validity of the short diffusion-time regime
      is demonstrated in vivo and ex vivo. Ex vivo measurements confirm that the purely
      geometric restrictions embodied in S/V are independent from temperature and
      frequency range, while the temperature dependence of the free diffusivity D0 is
      similar to that of pure water. CONCLUSION: Our results suggest that D(omega) in
      the short diffusion-time regime can be used to uncouple the purely geometric
      restriction effect, such as S/V, from the intrinsic medium diffusivity
      properties, and provides a nonempirical and objective way to interpret
      frequency/time-dependent diffusion changes in tumors in terms of objective
      biophysical tissue parameters. Magn Reson Med 76:237-247, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26207355
TI  - IV and IP administration of rhodamine in visualization of WBC-BBB interactions in
      cerebral vessels.
AB  - Epi-illuminescence intravital fluorescence microscopy has been employed to study
      leukocyte-endothelial interactions in a number of brain pathologies.
      Historically, dyes such as Rhodamine 6G have been injected intravenously.
      However, intravenous injections can predispose experimental animals to a
      multitude of complications and requires a high degree of technical skill. Here,
      we study the efficacy of injecting Rhodamine 6G into the peritoneum (IP) for the
      purpose of analyzing leukocyte-endothelial interactions through a cranial window
      during real time intravital microscopy. After examining the number of rolling and
      adherent leukocytes through a cranial window, we found no advantage to the
      intravenous injection (IV). Additionally, we tested blood from both routes of
      injection by flow cytometry to gain a very precise picture of the two methods.
      The two routes of administration failed to show any difference in the ability to
      detect cells. The study supports the notion that IP Rhodamine 6G works as
      efficaciously as IV and should be considered a viable alternative in experimental
      design for investigations employing intravital microscopy. Facilitated intravital
      studies will allow for more exploration into cerebral pathologies and allow for
      more rapid translation from the laboratory to the patient with less chance of
      experimental error from failed IV access.

PMID- 26207359
TI  - Mathematical models of alpha-synuclein transport in axons.
AB  - To investigate possible effects of diffusion on alpha-synuclein (alpha-syn)
      transport in axons, we developed two models of alpha-syn transport, one that
      assumes that alpha-syn is transported only by active transport, as part of
      multiprotein complexes, and a second that assumes an interplay between motor
      driven and diffusion-driven alpha-syn transport. By comparing predictions of the
      two models, we were able to investigate how diffusion could influence axonal
      transport of alpha-syn. The predictions obtained could be useful for future
      experimental work aimed at elucidating the mechanisms of axonal transport of
      alpha-syn. We also attempted to simulate possible defects in alpha-syn transport
      early in Parkinson's disease (PD). We assumed that in healthy axons alpha-syn
      localizes in the axon terminal while in diseased axons alpha-syn does not
      localize in the terminal (this was simulated by postulating a zero alpha-syn flux
      into the terminal). We found that our model of a diseased axon predicts the build
      up of alpha-syn close to the axon terminal. This build-up could cause alpha-syn
      accumulation in Lewy bodies and the subsequent axonal death pattern observed in
      PD ('dying back' of axons). 

PMID- 26207360
TI  - Abdominal Paracentesis Drainage: Which Patients With Severe Acute Pancreatitis
      Will Benefit?

PMID- 26207356
TI  - Phase 2 trial of sorafenib in children and young adults with refractory solid
      tumors: A report from the Children's Oncology Group.
AB  - BACKGROUND: Sorafenib is an oral small molecule inhibitor of multiple kinases
      controlling tumor growth and angiogenesis. The purpose of the phase 2 study was
      to determine the response rate of sorafenib and gain further information on the
      associated toxicities, pharmacokinetics, and pharmacodynamics of sorafenib in
      children and young adults with relapsed or refractory tumors including
      rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), and papillary
      thyroid carcinoma (PTC). PROCEDURE: Sorafenib, 200 mg/m(2) /dose, was
      administered every 12 hr continuously for 28 day cycles using a two-stage design
      in two primary strata (rhabdomyosarcoma and Wilms tumor) and two secondary strata
      (HCC and PTC). Correlative studies in consenting patients included determination
      of sorafenib steady state trough concentrations and assessments of VEGF and
      sVEGFR2. RESULTS: Twenty patients (median age of 11 years; range, 5-21) enrolled.
      No objective responses (RECIST) were observed in the 10 evaluable patients
      enrolled in each of the two primary disease strata of rhabdomyosarcoma and Wilms
      tumor. No patients with HCC or PTC were enrolled. Sorafenib was not associated
      with an excessive rate of dose-limiting toxicity (DLT). The mean +/- SD steady
      state concentration during cycle 1 day 15 was 6.5 +/- 3.9 MUg/ml (n = 10).
      CONCLUSIONS: Sorafenib was well tolerated in children at 200 mg/m(2) /dose twice
      daily on a continuous regimen with toxicity profile and steady state drug
      concentrations similar to those previously reported. Single agent sorafenib was
      inactive in children with recurrent or refractory rhabdomyosarcoma or Wilms
      tumor.

PMID- 26207363
TI  - An Observational Study of the Impact of a Computerized Physician Order Entry
      System on the Rate of Medication Errors in an Orthopaedic Surgery Unit.
AB  - AIM: To assess the impact of the implementation of a Computerized Physician Order
      Entry (CPOE) associated with a pharmaceutical checking of medication orders on
      medication errors in the 3 stages of drug management (i.e. prescription,
      dispensing and administration) in an orthopaedic surgery unit. METHODS: A before
      after observational study was conducted in the 66-bed orthopaedic surgery unit of
      a teaching hospital (700 beds) in Paris France. Direct disguised observation was
      used to detect errors in prescription, dispensing and administration of drugs,
      before and after the introduction of computerized prescriptions. Compliance
      between dispensing and administration on the one hand and the medical
      prescription on the other hand was studied. The frequencies and types of errors
      in prescribing, dispensing and administration were investigated. RESULTS: During
      the pre and post-CPOE period (two days for each period) 111 and 86 patients were
      observed, respectively, with corresponding 1,593 and 1,388 prescribed drugs. The
      use of electronic prescribing led to a significant 92% decrease in prescribing
      errors (479/1593 prescribed drugs (30.1%) vs 33/1388 (2.4%), p < 0.0001) and to a
      17.5% significant decrease in administration errors (209/1222 opportunities
      (17.1%) vs 200/1413 (14.2%), p < 0.05). No significant difference was found in
      regards to dispensing errors (430/1219 opportunities (35.3%) vs 449/1407 (31.9%),
      p = 0.07). CONCLUSION: The use of CPOE and a pharmacist checking medication
      orders in an orthopaedic surgery unit reduced the incidence of medication errors
      in the prescribing and administration stages. The study results suggest that CPOE
      is a convenient system for improving the quality and safety of drug management.

PMID- 26207364
TI  - A Comparison of Experimental and Analytical Procedures to Measure Passive Drag in
      Human Swimming.
AB  - The aim of this study was to compare the swimming hydrodynamics assessed with
      experimental and analytical procedures, as well as, to learn about the relative
      contributions of the friction drag and pressure drag to total passive drag. Sixty
      young talented swimmers (30 boys and 30 girls with 13.59+/-0.77 and 12.61+/-0.07
      years-old, respectively) were assessed. Passive drag was assessed with inverse
      dynamics of the gliding decay speed. The theoretical modeling included a set of
      analytical procedures based on naval architecture adapted to human swimming.
      Linear regression models between experimental and analytical procedures showed a
      high correlation for both passive drag (Dp = 0.777*Df+pr; R2 = 0.90; R2a = 0.90;
      SEE = 8.528; P<0.001) and passive drag coefficient (CDp = 1.918*CDf+pr; R2 =
      0.96; R2a = 0.96; SEE = 0.029; P<0.001). On average the difference between
      methods was -7.002N (95%CI: -40.480; 26.475) for the passive drag and 0.127
      (95%CI: 0.007; 0.247) for the passive drag coefficient. The partial contribution
      of friction drag and pressure drag to total passive drag was 14.12+/-9.33% and
      85.88+/-9.33%, respectively. As a conclusion, there is a strong relationship
      between the passive drag and passive drag coefficient assessed with experimental
      and analytical procedures. The analytical method is a novel, feasible and valid
      way to gather insight about one's passive drag during training and competition.
      Analytical methods can be selected not only to perform race analysis during
      official competitions but also to monitor the swimmer's status on regular basis
      during training sessions without disrupting or time-consuming procedures. 

PMID- 26207365
TI  - The Corn Smut ('Huitlacoche') as a New Platform for Oral Vaccines.
AB  - The development of new alternative platforms for subunit vaccine production is a
      priority in the biomedical field. In this study, Ustilago maydis, the causal
      agent of common corn smut or 'huitlacoche'has been genetically engineered to
      assess expression and immunogenicity of the B subunit of the cholera toxin (CTB),
      a relevant immunomodulatory agent in vaccinology. An oligomeric CTB recombinant
      protein was expressed in corn smut galls at levels of up to 1.3 mg g-1 dry weight
      (0.8% of the total soluble protein). Mice orally immunized with 'huitlacoche'
      derived CTB showed significant humoral responses that were well-correlated with
      protection against challenge with the cholera toxin (CT). These findings
      demonstrate the feasibility of using edible corn smut as a safe, effective, and
      low-cost platform for production and delivery of a subunit oral vaccine. The
      implications of this platform in the area of molecular pharming are discussed. 

PMID- 26207366
TI  - Botulinum Neurotoxins Can Enter Cultured Neurons Independent of Synaptic Vesicle
      Recycling.
AB  - Botulinum neurotoxins (BoNTs) are the causative agent of the severe and long
      lasting disease botulism. At least seven different serotypes of BoNTs (denoted A
      G) have been described. All BoNTs enter human or animal neuronal cells via
      receptor mediated endocytosis and cleave cytosolic SNARE proteins, resulting in a
      block of synaptic vesicle exocytosis, leading to the flaccid paralysis
      characteristic of botulism. Previous data have indicated that once a neuronal
      cell has been intoxicated by a BoNT, further entry of the same or other BoNTs is
      prevented due to disruption of synaptic vesicle recycling. However, it has also
      been shown that cultured neurons exposed to BoNT/A are still capable of taking up
      BoNT/E. In this report we show that in general BoNTs can enter cultured human or
      mouse neuronal cells that have previously been intoxicated with another BoNT
      serotype. Quantitative analysis of cell entry by assessing SNARE cleavage
      revealed none or only a minor difference in the efficiency of uptake of BoNTs
      into previously intoxicated neurons. Examination of the endocytic entry pathway
      by specific endocytosis inhibitors indicated that BoNTs are taken up by clathrin
      coated pits in both non pre-exposed and pre-exposed neurons. LDH release assays
      indicated that hiPSC derived neurons exposed consecutively to two different BoNT
      serotypes remained viable and healthy except in the case of BoNT/E or
      combinations of BoNT/E with BoNT/B, /D, or /F. Overall, our data indicate that
      previous intoxication of neuronal cells with BoNT does not inhibit further uptake
      of BoNTs. 

PMID- 26207367
TI  - Comparison of Methods for the Reconstruction of the Hepatic Artery in Mouse
      Orthotopic Liver Transplantation.
AB  - BACKGROUND: The mouse model of arterialized orthotopic liver transplantation
      (AOLT) has played an important role in biomedical research. The available methods
      of sutured anastomosis for reconstruction of the hepatic artery are complicated,
      resulting in a high incidence of complications and failure. Therefore, we
      developed and evaluated a new model of AOLT in mice. MATERIALS AND METHODS: Male
      inbred C57BL/6 mice were used in this study. A continuous suture approach was
      applied to connect the suprahepatic inferior vena cava (SHVC). The portal vein
      and infrahepatic inferior vena cava (IHVC) were connected according to the "two
      cuff" method. The common bile duct was connected by a biliary stent. We used the
      stent (G3 group) or aortic trunk (G2 group) to reconstruct the hepatic artery.
      The patency of the hepatic artery was verified by transecting the artery near the
      graft after one week. The survival rate of the recipients and serum alanine
      aminotransferase (ALT) levels, hepatic pathologic alterations, apoptosis and
      necrosis were observed at one week postoperatively. RESULTS: The patency of the
      hepatic artery was verified in eight of ten mice in G3 and in six of ten mice in
      G2. The 7-day survival rate, extents of necrosis and apoptosis, and TGF-beta
      levels were not significantly different among the three groups (P>0.05). However,
      the serum ALT levels and operation time were markedly lower in G3 compared with
      G2 or G1 (both P<0.05). CONCLUSIONS: Reconstruction of the hepatic artery using a
      stent can be performed quickly with a high rate of patency. This model simplifies
      hepatic artery anastomosis and should be promoted in the field of biomedical
      research.

PMID- 26207368
TI  - The Neighbourhood Built Environment and Trajectories of Depression Symptom
      Episodes in Adults: A Latent Class Growth Analysis.
AB  - AIM: To investigate the effect of the neighbourhood built environment on
      trajectories of depression symptom episodes in adults from the general Canadian
      population. RESEARCH DESIGN AND METHODS: We used 10 years of data collection
      (2000/01-2010/11) from the Canadian National Population Health Study (n = 7114).
      Episodes of depression symptoms were identified using the Composite International
      Diagnostic Interview Short-Form. We assessed the presence of local parks, healthy
      food stores, fast food restaurants, health services and cultural services using
      geospatial data. We used latent class growth modelling to identify different
      trajectories of depression symptom episodes in the sample and tested for the
      effect of neighbourhood variables on the trajectories over time. RESULTS: We
      uncovered three distinct trajectories of depression symptom episodes: low
      prevalence (76.2% of the sample), moderate prevalence (19.2%) and high prevalence
      of depression symptom episodes (2.8%). The presence of any neighbourhood service
      (healthy food store, fast-food restaurant, health service, except for cultural
      service) was significantly associated with a lower probability of a depression
      symptom episode for those following a trajectory of low prevalence of depression
      symptom episodes. The presence of a local park was also a significant protective
      factor in trajectory groups with both low and moderate prevalence of depression
      symptom episodes. Neighbourhood characteristics did not significantly affect the
      trajectory of high prevalence of depression symptom episodes. CONCLUSIONS: For
      individuals following a trajectory of low and moderate prevalence of depression
      symptom episodes, the neighbourhood built environment was associated with a shift
      in the trajectory of depression symptom episodes. Future intervention studies are
      recommended to make policy recommendations.

PMID- 26207369
TI  - Delayed Treatment with a Small Pigment Epithelium Derived Factor (PEDF) Peptide
      Prevents the Progression of Diabetic Renal Injury.
AB  - Our recent publication showed that a small bioactive pigment epithelium derived
      factor (PEDF) peptide (P78-PEDF) prevents the development of diabetic nephropathy
      (DN). However, its effects on the progression of established DN were not clear.
      Therefore, the purpose of this study was to determine the effect of P78-PEDF in
      the progression of DN and to compare the effects of P78-PEDF and an ACE inhibitor
      (ACEi), a standard of care in DN. Experiments were conducted in Ins2(Akita) mice
      treated with P78-PEDF or captopril starting at 6 wks of age for 12 wks (early
      treatment) or starting at 12 wks of age for 6 wks (late treatment). We first
      established the optimal dose of the P78-PEDF peptide to ameliorate DN in
      Ins2(Akita) mouse for a 6 wk study period and found that the peptide was
      effective at 0.1- 0.5 ug/g/day. We next showed that early or late treatment with
      P78-PEDF resulted in protection from DN as indicated by reduced albuminuria,
      kidney macrophage recruitment, histological changes, inflammatory cytokines and
      fibrotic markers (kidney TNF-alpha, fibronectin, VEGFA and EGFR), and restored
      nephrin expression compared with vehicle-treated Ins2(Akita) mice. Interestingly,
      only early but not late treatment with captopril was as effective as P78-PEDF in
      reducing most DN complications, despite its lack of effect on nephrin, VEGFA and
      EGFR expression. These findings highlight the importance of P78-PEDF peptide as a
      potential therapeutic modality in both the development and progression of
      diabetic renal injury.

PMID- 26207370
TI  - An Enriched European Eel Transcriptome Sheds Light upon Host-Pathogen
      Interactions with Vibrio vulnificus.
AB  - Infectious diseases are one of the principal bottlenecks for the European eel
      recovery. The aim of this study was to develop a new molecular tool to be used in
      host-pathogen interaction experiments in the eel. To this end, we first
      stimulated adult eels with different pathogen-associated molecular patterns
      (PAMPs), extracted RNA from the immune-related tissues and sequenced the
      transcriptome. We obtained more than 2 x 10(6) reads that were assembled and
      annotated into 45,067 new descriptions with a notable representation of novel
      transcripts related with pathogen recognition, signal transduction and the immune
      response. Then, we designed a DNA-microarray that was used to analyze the early
      immune response against Vibrio vulnificus, a septicemic pathogen that uses the
      gills as the portal of entry into the blood, as well as the role of the main
      toxin of this species (RtxA13) on this early interaction. The gill transcriptomic
      profiles obtained after bath infecting eels with the wild type strain or with a
      mutant deficient in rtxA13 were analyzed and compared. Results demonstrate that
      eels react rapidly and locally against the pathogen and that this immune-response
      is rtxA13-dependent as transcripts related with cell destruction were highly up
      regulated only in the gills from eels infected with the wild-type strain.
      Furthermore, significant differences in the immune response against the wild type
      and the mutant strain also suggest that host survival after V. vulnificus
      infection could depend on an efficient local phagocytic activity. Finally, we
      also found evidence of the presence of an interbranchial lymphoid tissue in
      European eel gills although further experiments will be necessary to identify
      such tissue.

PMID- 26207371
TI  - Clinical Evaluation of High-Volume Hemofiltration with Hemoperfusion Followed by
      Intermittent Hemodialysis in the Treatment of Acute Wasp Stings Complicated by
      Multiple Organ Dysfunction Syndrome.
AB  - Multiple organ dysfunction syndrome (MODS) is a rare complication of wasp stings.
      Currently, there is no standardized treatment for MODS secondary to multiple wasp
      stings, although blood purification techniques are often used. This study aimed
      to analyze our experiences of using intermittent hemodialysis (IHD) with or
      without high-volume hemofiltration (HVHF) for treating acute wasp stings
      complicated by MODS. In this retrospective study, 36 patients with wasp stings
      complicated by MODS received either IHD combined with hemoperfusion, or HVHF
      (ultrafiltration flow rate, 70 mL/kg/h) combined with hemoperfusion for 5 days
      followed by IHD. Clinical symptoms, blood biochemical parameters, duration of
      mechanical ventilation, use of vasoactive agents, duration of hospital stay and
      survival rate were recorded, and Acute Physiology and Chronic Health Evaluation
      II (APACHE II) and multiple organ dysfunction (MOD) scores estimated. Patients
      treated with HVHF followed by IHD appeared to exhibit a faster recovery than
      those receiving IHD alone, as evidenced by superior improvements in MOD (4.29+/
      1.08 vs. 2.27+/-1.07) and APACHE II (7.09+/-2.62 vs. 4.20+/-1.69) scores (P <
      0.05). Patients treated with HVHF had significantly lower myoglobin, creatine
      kinase-MB, lactate dehydrogenase, bilirubin and creatinine levels than patients
      treated with IHD alone. In addition, the durations of hospital stay (13.15+/-2.77
      vs. 27.92+/-3.18 days), vasopressor use (1.76+/-0.24 vs. 3.43 +/- 1.01 days),
      mechanical ventilation (3.02+/-1.63 vs. 5.94 +/- 2.11 days) and oliguria (6.57+/
      2.45 vs. 15.29 +/- 3.51 days) were reduced, and renal function more often
      recovered (85.1% vs. 53.1%), in the HVHF group compared with the IHD group (P <
      0.05). These results raise the possibility that HVHF plus IHD may be superior to
      IHD alone for the treatment of acute wasp stings complicated by MODS; additional
      prospective studies are merited to explore this further. 

PMID- 26207375
TI  - Correction: Doxycycline Induces Apoptosis and Inhibits Proliferation and Invasion
      of Human Cervical Carcinoma Stem Cells.

PMID- 26207373
TI  - Diversity and Genetic Variation among Brevipalpus Populations from Brazil and
      Mexico.
AB  - Brevipalpus phoenicis s.l. is an economically important vector of the Citrus
      leprosis virus-C (CiLV-C), one of the most severe diseases attacking citrus
      orchards worldwide. Effective control strategies for this mite should be designed
      based on basic information including its population structure, and particularly
      the factors that influence its dynamics. We sampled sweet orange orchards
      extensively in eight locations in Brazil and 12 in Mexico. Population genetic
      structure and genetic variation between both countries, among locations and among
      sampling sites within locations were evaluated by analysing nucleotide sequence
      data from fragments of the mitochondrial cytochrome oxidase subunit I (COI). In
      both countries, B. yothersi was the most common species and was found in almost
      all locations. Individuals from B. papayensis were found in two locations in
      Brazil. Brevipalpus yothersi populations collected in Brazil were more
      genetically diverse (14 haplotypes) than Mexican populations (four haplotypes).
      Although geographical origin had a low but significant effect (ca. 25%) on the
      population structure, the greatest effect was from the within location comparison
      (37.02 %). Potential factors driving our results were discussed. 

PMID- 26207372
TI  - Chlamydia trachomatis In Vivo to In Vitro Transition Reveals Mechanisms of Phase
      Variation and Down-Regulation of Virulence Factors.
AB  - Research on the obligate intracellular bacterium Chlamydia trachomatis demands
      culture in cell-lines, but the adaptive process behind the in vivo to in vitro
      transition is not understood. We assessed the genomic and transcriptomic dynamics
      underlying C. trachomatis in vitro adaptation of strains representing the three
      disease groups (ocular, epithelial-genital and lymphogranuloma venereum)
      propagated in epithelial cells over multiple passages. We found genetic features
      potentially underlying phase variation mechanisms mediating the regulation of a
      lipid A biosynthesis enzyme (CT533/LpxC), and the functionality of the cytotoxin
      (CT166) through an ON/OFF mechanism. We detected inactivating mutations in
      CT713/porB, a scenario suggesting metabolic adaptation to the available carbon
      source. CT135 was inactivated in a tropism-specific manner, with CT135-negative
      clones emerging for all epithelial-genital populations (but not for LGV and
      ocular populations) and rapidly increasing in frequency (~23% mutants per 10
      passages). RNA-sequencing analyses revealed that a deletion event involving CT135
      impacted the expression of multiple virulence factors, namely effectors known to
      play a role in the C. trachomatis host-cell invasion or subversion (e.g.,
      CT456/Tarp, CT694, CT875/TepP and CT868/ChlaDub1). This reflects a scenario of
      attenuation of C. trachomatis virulence in vitro, which may take place
      independently or in a cumulative fashion with the also observed down-regulation
      of plasmid-related virulence factors. This issue may be relevant on behalf of the
      recent advances in Chlamydia mutagenesis and transformation where culture
      propagation for selecting mutants/transformants is mandatory. Finally, there was
      an increase in the growth rate for all strains, reflecting gradual fitness
      enhancement over time. In general, these data shed light on the adaptive process
      underlying the C. trachomatis in vivo to in vitro transition, and indicates that
      it would be prudent to restrict culture propagation to minimal passages and check
      the status of the CT135 genotype in order to avoid the selection of CT135
      negative mutants, likely originating less virulent strains. 

PMID- 26207376
TI  - Predicting Variabilities in Cardiac Gene Expression with a Boolean Network
      Incorporating Uncertainty.
AB  - Gene interactions in cells can be represented by gene regulatory networks. A
      Boolean network models gene interactions according to rules where gene expression
      is represented by binary values (on / off or {1, 0}). In reality, however, the
      gene's state can have multiple values due to biological properties. Furthermore,
      the noisy nature of the experimental design results in uncertainty about a state
      of the gene. Here we present a new Boolean network paradigm to allow intermediate
      values on the interval [0, 1]. As in the Boolean network, fixed points or
      attractors of such a model correspond to biological phenotypes or states. We use
      our new extension of the Boolean network paradigm to model gene expression in
      first and second heart field lineages which are cardiac progenitor cell
      populations involved in early vertebrate heart development. By this we are able
      to predict additional biological phenotypes that the Boolean model alone is not
      able to identify without utilizing additional biological knowledge. The
      additional phenotypes predicted by the model were confirmed by published
      biological experiments. Furthermore, the new method predicts gene expression
      propensities for modelled but yet to be analyzed genes. 

PMID- 26207377
TI  - A Novel Mutation of DAX-1 Associated with Secretory Azoospermia.
AB  - Secretory azoospermia is a severe form of male infertility caused by unknown
      factors. DAX-1 is predominantly expressed in mammalian reproductive tissues and
      plays an important role in spermatogenesis because Dax-1 knockout male mice show
      spermatogenesis defects. To examine whether DAX-1 is involved in the pathogenesis
      of secretory azoospermia in humans, we sequenced all of the exons of DAX-1 in 776
      patients diagnosed with secretory azoospermia and 709 proven fertile men. A
      number of coding mutations unique to the patient group, including two synonymous
      mutations and six missense mutations, were identified. Of the missense mutations,
      our functional assay demonstrated that the V385L mutation caused the reduced
      functioning of DAX-1. This novel mutation (p. V385L) of DAX-1 is the first to be
      identified in association with secretory azoospermia, thereby highlighting the
      important role of DAX-1 in spermatogenesis. 

PMID- 26207374
TI  - Two Virus-Induced MicroRNAs Known Only from Teleost Fishes Are Orthologues of
      MicroRNAs Involved in Cell Cycle Control in Humans.
AB  - MicroRNAs (miRNAs) are ~22 base pair-long non-coding RNAs which regulate gene
      expression in the cytoplasm of eukaryotic cells by binding to specific target
      regions in mRNAs to mediate transcriptional blocking or mRNA cleavage. Through
      their fundamental roles in cellular pathways, gene regulation mediated by miRNAs
      has been shown to be involved in almost all biological phenomena, including
      development, metabolism, cell cycle, tumor formation, and host-pathogen
      interactions. To address the latter in a primitive vertebrate host, we here used
      an array platform to analyze the miRNA response in rainbow trout (Oncorhynchus
      mykiss) following inoculation with the virulent fish rhabdovirus Viral
      hemorrhagic septicaemia virus. Two clustered miRNAs, miR-462 and miR-731 (herein
      referred to as miR-462 cluster), described only in teleost fishes, were found to
      be strongly upregulated, indicating their involvement in fish-virus interactions.
      We searched for homologues of the two teleost miRNAs in other vertebrate species
      and investigated whether findings related to ours have been reported for these
      homologues. Gene synteny analysis along with gene sequence conservation suggested
      that the teleost fish miR-462 and miR-731 had evolved from the ancestral miR-191
      and miR-425 (herein called miR-191 cluster), respectively. Whereas the miR-462
      cluster locus is found between two protein-coding genes (intergenic) in teleost
      fish genomes, the miR-191 cluster locus is found within an intron of a protein
      coding gene (intragenic) in the human genome. Interferon (IFN)-inducible and
      immune-related promoter elements found upstream of the teleost miR-462 cluster
      locus suggested roles in immune responses to viral pathogens in fish, while in
      humans, the miR-191 cluster functionally associated with cell cycle regulation.
      Stimulation of fish cell cultures with the IFN inducer poly I:C accordingly
      upregulated the expression of miR-462 and miR-731, while no stimulatory effect on
      miR-191 and miR-425 expression was observed in human cell lines. Despite high
      sequence conservation, evolution has thus resulted in different regulation and
      presumably also different functional roles of these orthologous miRNA clusters in
      different vertebrate lineages. 

PMID- 26207378
TI  - Patterns and Determinants of Habitat Occupancy by the Asian Elephant in the
      Western Ghats of Karnataka, India.
AB  - Understanding species distribution patterns has direct ramifications for the
      conservation of endangered species, such as the Asian elephant Elephas maximus.
      However, reliable assessment of elephant distribution is handicapped by factors
      such as the large spatial scales of field studies, survey expertise required, the
      paucity of analytical approaches that explicitly account for confounding
      observation processes such as imperfect and variable detectability, unequal
      sampling probability and spatial dependence among animal detections. We addressed
      these problems by carrying out 'detection--non-detection' surveys of elephant
      signs across a c. 38,000-km(2) landscape in the Western Ghats of Karnataka,
      India. We analyzed the resulting sign encounter data using a recently developed
      modeling approach that explicitly addresses variable detectability across space
      and spatially dependent non-closure of occupancy, across sampling replicates. We
      estimated overall occupancy, a parameter useful to monitoring elephant
      populations, and examined key ecological and anthropogenic drivers of elephant
      presence. Our results showed elephants occupied 13,483 km(2) (SE = 847 km(2))
      corresponding to 64% of the available 21,167 km(2) of elephant habitat in the
      study landscape, a useful baseline to monitor future changes. Replicate-level
      detection probability ranged between 0.56 and 0.88, and ignoring it would have
      underestimated elephant distribution by 2116 km(2) or 16%. We found that
      anthropogenic factors predominated over natural habitat attributes in determining
      elephant occupancy, underscoring the conservation need to regulate them. Human
      disturbances affected elephant habitat occupancy as well as site-level
      detectability. Rainfall is not an important limiting factor in this relatively
      humid bioclimate. Finally, we discuss cost-effective monitoring of Asian elephant
      populations and the specific spatial scales at which different population
      parameters can be estimated. We emphasize the need to model the observation and
      sampling processes that often obscure the ecological process of interest, in this
      case relationship between elephants to their habitat.

PMID- 26207379
TI  - Proton Diffusivity in the Protic Ionic Liquid Triethylammonium Triflate Probed by
      Quasielastic Neutron Scattering.
AB  - Quasielastic neutron scattering (QENS) in combination with deuterium labeling
      allows for studying protonated "highlighted" species and extracting detailed
      information about tangled stochastic processes. This approach has been applied to
      examine proton dynamics in the protic ionic liquid, triethylammonium triflate.
      The temperature range covered during the experiments (2-440 K) included two
      melting transitions correspondingly reflected in the global and localized
      dynamics of the cation. To focus on the dynamics of the acidic proton, QENS
      spectra of the sample with the deuterated alkyl side chains were analyzed. The
      remaining hydrogen atom served as a tagged particle for investigating both global
      long-range motion of the cation and specific dynamics of the proton and, thus,
      provided insight into the transport properties of triethylammonium triflate,
      which is important for designing electrochemical devices. 

PMID- 26207380
TI  - Cholangiocarcinoma: Correlation between Molecular Profiling and Imaging
      Phenotypes.
AB  - PURPOSE: To investigate associations between imaging features of
      cholangiocarcinoma by visual assessment and texture analysis, which quantifies
      heterogeneity in tumor enhancement patterns, with molecular profiles based on
      hypoxia markers. METHODS: The institutional review board approved this HIPAA
      compliant retrospective study of CT images of intrahepatic cholangiocarcinoma,
      obtained before surgery. Immunostaining for hypoxia markers (EGFR, VEGF, CD24,
      P53, MDM2, MRP-1, HIF-1alpha, CA-IX, and GLUT1) was performed on pre-treatment
      liver biopsies. Quantitative imaging phenotypes were determined by texture
      analysis with gray level co-occurrence matrixes. The correlations between
      quantitative imaging phenotypes, qualitative imaging features (measured by
      radiographic inspection alone), and expression levels of the hypoxia markers from
      the 25 tumors were assessed. RESULTS: Twenty-five patients were included with a
      median age of 62 years (range: 54-84). The median tumor size was 10.2 cm (range:
      4-14), 10 (40%) were single tumors, and 90% were moderately differentiated.
      Positive immunostaining was recorded for VEGF in 67% of the cases, EGFR in 75%,
      and CD24 in 55%. On multiple linear regression analysis, quantitative imaging
      phenotypes correlated significantly with EGFR and VEGF expression levels (R2 =
      0.4, p<0.05 and R2 = 0.2, p<0.05, respectively), while a trend was demonstrated
      with CD24 expression (R2 = 0.33, p = 0.1). Three qualitative imaging features
      correlated with VEGF and CD24 expression (P<0.05), however, none of the
      qualitative features correlated with the quantitative imaging phenotypes.
      CONCLUSION: Quantitative imaging phenotypes, as defined by texture analysis,
      correlated with expression of specific markers of hypoxia, regardless of
      conventional imaging features.

PMID- 26207381
TI  - Reduced Expression of TET1, TET2, TET3 and TDG mRNAs Are Associated with Poor
      Prognosis of Patients with Early Breast Cancer.
AB  - PURPOSE: The purpose of this study was to determine the prognostic role of ten
      eleven translocation (TET) family proteins and DNA glycosylase (TDG) in patients
      with early breast cancer (EBC). METHODS: Expression of mRNAs encoding TET1-3 and
      TDG in 162 breast cancer tissues was quantified using real-time polymerase chain
      reaction analysis. The general characteristics of patients and clinicopathologic
      factors were collected. Estimation of patient survival was calculated using the
      Kaplan-Meier method, and independent prognostic indicators were analyzed using
      Cox regression analysis. RESULTS: The level of TET1 mRNA was significantly
      related to overall survival (OS) (P = 0.022). Multivariate analysis shows that
      the TNM stage was an independent predictor of disease-free survival (DFS) (HR =
      1.761, 95% CI: 1.124-2.761, P = 0.014) and OS (HR = 2.135, 95% CI: 1.070-4.263, P
      = 0.032). Further, in patients with EBC who were treated with anthracyclines,
      Kaplan-Meier analysis indicates that the levels of TET3 and TDG mRNAs were
      related to DFS (P = 0.026 and 0.030, respectively), and multivariate analysis
      reveals that high levels of TET3 (HR = 1.944, 95% CI: 1.029-3.672, P = 0.040) and
      TDG (HR = 2.178, 95% CI: 1.140-4.163, P = 0.018) mRNAs were independent
      indicators of favorable DFS. CONCLUSIONS: Our study indicates that EBC patients
      with decreased expression of TET1 mRNA had worse OS and that the levels of TET3
      and TDG mRNAs were independent prognostic factors for patients who received
      anthracycline chemotherapy.

PMID- 26207382
TI  - Detection of Rickettsia and Ehrlichia spp. in Ticks Associated with Exotic
      Reptiles and Amphibians Imported into Japan.
AB  - One of the major routes of transmission of rickettsial and ehrlichial diseases is
      via ticks that infest numerous host species, including humans. Besides mammals,
      reptiles and amphibians also carry ticks that may harbor Rickettsia and Ehrlichia
      strains that are pathogenic to humans. Furthermore, reptiles and amphibians are
      exempt from quarantine in Japan, thus facilitating the entry of parasites and
      pathogens to the country through import. Accordingly, in the current study, we
      examined the presence of Rickettsia and Ehrlichia spp. genes in ticks associated
      with reptiles and amphibians originating from outside Japan. Ninety-three ticks
      representing nine tick species (genera Amblyomma and Hyalomma) were isolated from
      at least 28 animals spanning 10 species and originating from 12 countries (Ghana,
      Jordan, Madagascar, Panama, Russia, Sri Lanka, Sudan, Suriname, Tanzania, Togo,
      Uzbekistan, and Zambia). None of the nine tick species are indigenous in Japan.
      The genes encoding the common rickettsial 17-kDa antigen, citrate synthase
      (gltA), and outer membrane protein A (ompA) were positively detected in 45.2%
      (42/93), 40.9% (38/93), and 23.7% (22/93) of the ticks, respectively, by
      polymerase chain reaction (PCR). The genes encoding ehrlichial heat shock protein
      (groEL) and major outer membrane protein (omp-1) were PCR-positive in 7.5% (7/93)
      and 2.2% (2/93) of the ticks, respectively. The p44 gene, which encodes the
      Anaplasma outer membrane protein, was not detected. Phylogenetic analysis showed
      that several of the rickettsial and ehrlichial sequences isolated in this study
      were highly similar to human pathogen genes, including agents not previously
      detected in Japan. These data demonstrate the global transportation of pathogenic
      Rickettsia and Ehrlichia through reptile- and amphibian-associated ticks. These
      imported animals have potential to transfer pathogens into human life. These
      results highlight the need to control the international transportation of known
      and potential pathogens carried by ticks in reptiles, amphibians, and other
      animals, in order to improve national and international public health. 

PMID- 26207383
TI  - Combined Usefulness of the Platelet-to-Lymphocyte Ratio and the Neutrophil-to
      Lymphocyte Ratio in Predicting the Long-Term Adverse Events in Patients Who Have
      Undergone Percutaneous Coronary Intervention with a Drug-Eluting Stent.
AB  - OBJECTIVES: The aim of this study was to investigate the combined usefulness of
      platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in
      predicting the long-term adverse events in patients who have undergone
      percutaneous coronary intervention (PCI) with a drug-eluting stent (DES).
      METHODS: 798 patients with stable angina, unstable angina and non-ST elevated
      myocardial infarction (NSTEMI) who underwent elective successful PCI with DES
      were consecutively enrolled. The value of PLR and NLR in predicting adverse
      coronary artery disease (CAD) events and the correlations between these markers
      and adverse events (all-cause mortality, cardiac death, and nonfatal myocardial
      infarction) were analyzed. RESULTS: The follow-up period was 62.8 +/- 28.8
      months. When patients were classified into four groups according to the optimal
      cut-off values for the PLR and NLR on receiver operating characteristic analysis,
      patients with a high PLR (>128) and high NLR (>2.6) had the highest occurrence of
      adverse events among the groups. On Cox multivariate analysis, the NLR >2.6
      [hazard ratio (HR) 2.352, 95% confidence interval (CI) 1.286 to 4.339, p = 0.006]
      and the PLR >128 (HR 2.372, 95% CI 1.305 to 3.191, p = 0.005) were independent
      predictors of long-term adverse events after adjusting for cardiovascular risk
      factors. Moreover, both a PLR >128 and a NLR >2.6 were the strongest predictors
      of adverse events (HR 2.686, 95% CI 1.452 to 4.970, p = 0.002). CONCLUSION: High
      pre-intervention PLR and NLR, especially when combined, are independent
      predictors of long-term adverse clinical outcomes such as all-cause mortality,
      cardiac death, and myocardial infarction in patients with unstable angina and
      NSTEMI who have undergone successful PCI with DES.

PMID- 26207384
TI  - The Influence of the Autoimmunity-Associated Ancestral HLA Haplotype AH8.1 on the
      Human Gut Microbiota: A Cross-Sectional Study.
AB  - Multiple immune-related genes are encoded in the HLA complex on chromosome 6p21.
      The 8.1 ancestral haplotype (AH8.1) include the classical HLA alleles HLA-B*08:01
      and HLA-DRB1*03:01, and has been associated with a large number of autoimmune
      diseases, but the underlying mechanisms for this association are largely unknown.
      Given the recently established links between the gut microbiota and inflammatory
      diseases, we hypothesized that the AH8.1 influences the host gut microbial
      community composition. To study this further, healthy individuals were selected
      from the Norwegian Bone Marrow Donor Registry and categorized as either I. AH8.1
      homozygote (n=34), II. AH8.1 heterozygote (n=38), III. Non AH8.1 heterozygote or
      IV. HLA-DRB1 homozygote but non AH8.1 (n=15). Bacterial DNA from stool samples
      were subjected to sequencing of the V3-V5 region of the 16S rRNA gene on the 454
      Life Sciences platform and data analyzed using Mothur and QIIME. The results
      showed that the abundances of different taxa were highly variable within all pre
      defined AH8.1 genotype groups. Using univariate non-parametric statistics, there
      were no differences regarding alpha or beta diversity between AH8.1 carriers
      (categories I and II) and non-carriers (categories III and IV), however four
      different taxa (Prevotellaceae, Clostridium XVIII, Coprococcus, Enterorhabdus)
      had nominally significant lower abundances in AH8.1 carriers than non-carriers.
      After including possible confounders in a multivariate linear regression, only
      the two latter genera remained significantly associated. In conclusion, the
      overall contribution of the AH8.1 haplotype to the variation in gut microbiota
      profile of stool in the present study was small. 

PMID- 26207386
TI  - Validation and Application of the Mass Balance Model To Determine the
      Effectiveness of Portable Air Purifiers in Removing Ultrafine and Submicrometer
      Particles in an Apartment.
AB  - We validated the use of the mass balance model to determine the effectiveness of
      portable air purifiers in removing ultrafine (<0.10 MUm) and submicrometer
      particles (0.10-0.53 MUm) in an apartment. We evaluated two identical portable
      air purifiers, equipped with high efficiency particulate air filters, for their
      performance under three different air flow settings and three target air exchange
      rates: 0.60, 0.90, and 1.20 h(-1). We subsequently used a mixed effects model to
      estimate the slope between the measured and modeled effectiveness by particle
      size. Our study showed that effectiveness was highly particle size-dependent. For
      example, at the lowest target air exchange rate, it ranged from 0.33 to 0.56,
      0.51 to 0.75, and 0.60 to 0.81 for the three air purifier flow settings,
      respectively. Our findings suggested that filtration was the dominant removal
      mechanism for submicrometer particles, whereas deposition could play a more
      important role in ultrafine particle removal. We found reasonable agreement
      between measured and modeled effectiveness with size-resolved slopes ranging from
      1.11 +/- 0.06 to 1.25 +/- 0.07 (mean +/- SE), except for particles <35 nm. Our
      study design can be applied to investigate the performances of other portable air
      purifiers as well as the influences of various parameters on effectiveness in
      different residential settings.

PMID- 26207385
TI  - Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal
      Asthma.
AB  - Globally, asthma is a chronic inflammatory respiratory disease affecting over 300
      million people. Some asthma patients remain poorly controlled by conventional
      therapies and experience more life-threatening exacerbations. Vitamin D, as an
      adjunct therapy, may improve disease control in severe asthma patients since
      vitamin D enhances glucocorticoid responsiveness and mitigates airway smooth
      muscle (ASM) hyperplasia. We sought to characterize differences in transcriptome
      responsiveness to vitamin D between fatal asthma- and non-asthma-derived ASM by
      using RNA-Seq to measure ASM transcript expression in five donors with fatal
      asthma and ten non-asthma-derived donors at baseline and with vitamin D
      treatment. Based on a Benjamini-Hochberg corrected p-value <0.05, 838 genes were
      differentially expressed in fatal asthma vs. non-asthma-derived ASM at baseline,
      and vitamin D treatment compared to baseline conditions induced differential
      expression of 711 and 867 genes in fatal asthma- and non-asthma-derived ASM,
      respectively. Functional gene categories that were highly represented in all
      groups included extracellular matrix, and responses to steroid hormone stimuli
      and wounding. Genes differentially expressed by vitamin D also included cytokine
      and chemokine activity categories. Follow-up qPCR and individual analyte ELISA
      experiments were conducted for four cytokines (i.e. CCL2, CCL13, CXCL12, IL8) to
      measure TNFalpha-induced changes by asthma status and vitamin D treatment.
      Vitamin D inhibited TNFalpha-induced IL8 protein secretion levels to a comparable
      degree in fatal asthma- and non-asthma-derived ASM even though IL8 had
      significantly higher baseline levels in fatal asthma-derived ASM. Our findings
      identify vitamin D-specific gene targets and provide transcriptomic data to
      explore differences in the ASM of fatal asthma- and non-asthma-derived donors. 

PMID- 26207387
TI  - Subthalamic stimulation: toward a simplification of the electrophysiological
      procedure.
AB  - BACKGROUND: The aim of the present study was to assess the consequences of a
      simplification of the electrophysiological procedure on the post-operative
      clinical outcome after subthalamic nucleus implantation in Parkinson disease.
      METHODS: Microelectrode recordings were performed on 5 parallel trajectories in
      group 1 and less than 5 trajectories in group 2. Clinical evaluations were
      performed 1 month before and 6 months after surgery. RESULTS: After surgery, the
      UPDRS III score in the off-drug/on-stimulation and on-drug/on-stimulation
      conditions significantly improved by 66,9% and 82%, respectively in group 1, and
      by 65.8% and 82.3% in group 2 (P<0.05). Meanwhile, the total number of words
      (P<0.05) significantly decreased for fluency tasks in both groups. Motor
      disability improvement and medication reduction were similar in both groups.
      CONCLUSIONS: Our results suggest that the electrophysiological procedure should
      be simplified as the team's experience increases.

PMID- 26207388
TI  - Performance study of compounded biocover material for methane removal based on
      cattle manure compost.
AB  - Methane is the second most significant greenhouse gas. Landfill cover soils play
      an important role in mitigation of methane emission from critical sources -
      Landfills. In this study, methane removal biocover materials based on cattle
      manure compost (CMC) were constructed and its performance was investigated. When
      comparing CH4 removal abilities of sand (S), clay soil (CS), paddy soil (PS) and
      CMC, CMC was the most effective biocover material for the reduction of methane
      emission. The maximum removal rate (Vmax) and half saturation constant (Km) of
      CMC peaked at 3451.25 +/- 18.57 MUg g(-1) h(-1) and 3.67 +/- 0.02 * 10(5) ppm,
      respectively, which are higher than those in previous studies. Thereafter, three
      compounded biocover materials (CBMs) were established based on the mixture of CMC
      and other three materials (ratio of 2:8). The rate of the three CBMs was enhanced
      by 13.56, 13.27 and 16.42 times, respectively, more than the S, CS and PS by
      adding CMC. Saturated water content of 80% and 35  degrees C were found to be the
      optimum moisture and temperature, respectively, for CBMs. Analysis of community
      diversity using terminal restriction fragment length polymorphism (T-RFLP) showed
      that the diversity and evenness indexes of the CBMs decreased after adding CMC;
      Type I methanotroph was the most dominated methanotroph in the CBMs. CMC not only
      influenced bacterial community but also improved nutrient and CH4 removal
      capacity of CBMs. All results showed that CMC and CBMs could effectively remove
      CH4, and the screening and construction of CBMs are important for decreasing CH4
      emission.

PMID- 26207391
TI  - Primary Cutaneous Ewing Sarcoma: Report of a Case.
AB  - Primary cutaneous Ewing's sarcoma is a rare entity. Although the diagnosis may be
      very difficult, it can be confirmed through molecular biology. We present the
      case of a 13-years old male with a lesion in the sole of the right foot,
      characterized by a monomorphous proliferation of small, round and blue cells. The
      histology and molecular biology allowed us to perform the diagnosis of cutaneous
      Ewing's sarcoma. This neoplasm must be distinguished from other round cell tumors
      with cutaneous involvement. The prognosis and treatment of this rare disease will
      also be discussed.

PMID- 26207392
TI  - Trends in Susceptibility Rates and Extended-Spectrum beta-Lactamase Production of
      Klebsiella pneumoniae in Bloodstream Infections Across the United States Veterans
      Affairs Healthcare System.
AB  - Klebsiella pneumoniae is an important pathogen, increasingly notorious for its
      ability to become resistant to antimicrobial agents. This study sought to
      characterize trends in antimicrobial susceptibility rates for K. pneumoniae
      causing bacteremias across the United States (U.S.) Veterans Healthcare
      Administration (VHA) from 2007 through 2013 utilizing a national clinical
      database. K. pneumoniae grew in 9,235 blood cultures from 8,414 patients.
      Nationally, ampicillin-sulbactam, ceftazidime, cefepime, ertapenem,
      fluoroquinolones, and amikacin demonstrated statistically significant
      susceptibility rate increases against K. pneumoniae in the 2010-2013 period
      versus the 2007-2009 period. No antimicrobial agent had a statistically
      significant nationwide susceptibility rate decrease. Of the 126 antibiotic
      organism pairs tested among 9 U.S. regions, 18 demonstrated statistically
      significant susceptibility rate increases while 6 demonstrated statistically
      significant susceptibility rate decreases. The East North Central (eight agents),
      Mid-Atlantic (five agents), and South Atlantic (four agents) regions demonstrated
      statistically significant susceptibility rate increases for multiple
      antimicrobial agents. Of the 70 antibiotic-organism pairs tested among 5
      different medical center complexity levels, 11 antibiotics demonstrated
      statistically significant susceptibility rate increases and 1 demonstrated a
      statistically significant rate decrease. Extended-spectrum beta-lactamase
      production did not significantly change over the study period across an available
      nationwide representation of 31 facilities (10.6% in 2007-2009 vs. 9.21% in 2010
      2013, p=0.17). The South Atlantic and Mid-Atlantic regions had the highest
      prevalence of extended-spectrum beta-lactamase production in the two periods,
      respectively. The recent trend of generally increasing susceptibility rates for
      K. pneumoniae bloodstream isolates in this nationwide U.S. VHA study contrasts
      from other U.S. health system reports demonstrating increasing trends of
      antimicrobial resistance. 

PMID- 26207394
TI  - Holding on to hope: A review of the literature exploring missing persons, hope
      and ambiguous loss.
AB  - When a person goes missing, those left behind mourn an ambiguous loss where grief
      can be disenfranchised. Different to bereavement following death, hope figures
      into this experience as a missing person has the potential to return. This review
      explores hope for families of missing people. Lived experience of ambiguous loss
      was deconstructed to reveal responses punctuated by hope, which had practical and
      psychological implications for those learning to live with an unresolved absence.
      Future lines of enquiry must address the dearth of research exploring the role of
      hope, unresolved grief, and its clinical implications when a person is missing. 

PMID- 26207396
TI  - Thrombocytopenia Associated with Linezolid Therapy in Solid Organ Transplant
      Recipients: A Retrospective Cohort Study.
AB  - BACKGROUND: Linezolid is associated infrequently with bone marrow suppression in
      immunocompetent patients, but hematologic complications from linezolid in
      transplant recipients are understudied. This study evaluated the hematologic
      safety of linezolid in solid organ transplant recipients. METHODS: We performed a
      retrospective study of inpatients at our institution treated with linezolid from
      June 1, 2009 until June 6, 2012. The solid organ transplant cohort (TP) was
      compared with the non-transplant cohort (NTP) using parameters related to
      linezolid safety. Outcomes included incidences of leukopenia or thrombocytopenia
      at the end of linezolid treatment (EOT), lengths of stay, and blood product
      requirements. RESULTS: The TP cohort included 110 patients; the NTP cohort
      included 583 patients. Baseline parameters were similar between the TP and NTP
      cohorts. Non-transplant patients were more likely to have methicillin-resistant
      Staphylococcus aureus (MRSA), whereas TP patients received more doses of
      linezolid (17.0 vs. 11.3, p<0.001) and were more likely to receive other drugs
      associated with thrombocytopenia (91.7% vs. 11.3%, p<0.0001). Transplant patients
      with normal platelet counts at baseline were more likely to have EOT
      thrombocytopenia (29.3% vs. 10.7%, p=0.005), and multivariable regression
      analysis confirmed only a beginning platelet count less than 150,000 platelets
      per micoliter to be significantly different between groups: 43% TP versus 26.9%
      NTP (p=0.0009) making it the only independent predictor of EOT thrombocytopenia.
      Finally, TP patients were more likely to require platelet transfusions compared
      with the NTP cohort. CONCLUSIONS: Transplant patients who received linezolid had
      a higher incidence of EOT thrombocytopenia and platelet transfusions, compared
      with NTP. Transplant patients who are thrombocytopenic at baseline are at the
      greatest risk. These findings may relate to more frequent use of drugs associated
      with marrow suppression or greater linezolid exposure in the TP cohort.
      Clinicians caring for transplant patients should take into account this higher
      risk of thrombocytopenia and need for platelets when considering use of linezolid
      in this population.

PMID- 26207397
TI  - Screening for Ventilator-Associated Pneumonia in the Surgical Intensive Care
      Unit: A Single-Institution Analysis of 1,013 Lower Respiratory Tract Cultures.
AB  - BACKGROUND: Refinement of criteria for both screening and initiation of empiric
      therapy in ventilator-associated pneumonia (VAP) will minimize antibiotic
      overuse. We hypothesized that variables within the commonly used Clinical
      Pulmonary Infection Score (CPIS) have unfavorable test performance
      characteristics. METHODS: Consecutive bronchoalveolar lavage (BAL) cultures
      obtained from surgical intensive care unit patients were abstracted (2009-2012).
      Ventilator-associated pneumonia was defined as >=10(5) cfu/mL. The CPIS both
      without (CPISclinical) and with (CPISclinical+GS) the result of gram stain (GS)
      was calculated. Test performance characteristics for the sample, as well as
      several subgroups, were compared. RESULTS: One thousand thirteen lower
      respiratory tract cultures from 492 patients were analyzed; 438 (43.2%) of
      cultures were classified as VAP, and 310 of 492 patients (62.4%) had >=1 episode
      of VAP. Both CPISclinical and CPISclinical+GS had poor discrimination for VAP
      (Receiver-operating characteristic area under the curve=0.55 and 0.66,
      respectively). Sensitivity of CPISclinical using a threshold of >6 was 21%; the
      lowest threshold for CPISclinical for which the sensitivity was at least 85% was
      3. The highest sensitivity among the individual CPIS components was new CXR
      infiltrate (91.1%). Among the subset of cultures sent during the early VAP window
      (days intubated 2-5), organisms on GS had a sensitivity of 93.3%. The
      CPISclinical, CPISclinical+GS, organisms, and neutrophils on GS parameters all
      became less accurate in both the late VAP window and when screening for recurrent
      VAP. Every case of VAP had at least one of the following: 1) fever; 2) new CXR
      infiltrate, or 3) organisms on GS. CONCLUSION: In this series of BALs,
      traditional screening tools for VAP missed the majority of microbiological
      confirmed cases. Screening based on either new CXR infiltrate or fever yielded an
      acceptably high sensitivity. The only scenario identified in which empiric
      antibiotics could be withheld safely was the absence of organisms on GS in the
      early VAP window.

PMID- 26207393
TI  - Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson
      disease.
AB  - Parkinson disease (PD), once considered as a prototype of a sporadic disease, is
      now known to be considerably affected by various genetic factors, which interact
      with environmental factors and the normal process of aging, leading to PD. Large
      studies determined that the hereditary component of PD is at least 27%, and in
      some populations, single genetic factors are responsible for more than 33% of PD
      patients. Interestingly, many of these genetic factors, such as LRRK2, GBA,
      SMPD1, SNCA, PARK2, PINK1, PARK7, SCARB2, and others, are involved in the
      autophagy-lysosome pathway (ALP). Some of these genes encode lysosomal enzymes,
      whereas others correspond to proteins that are involved in transport to the
      lysosome, mitophagy, or other autophagic-related functions. Is it possible that
      all these factors converge into a single pathway that causes PD? In this review,
      we will discuss these genetic findings and the role of the ALP in the
      pathogenesis of PD and will try to answer this question. We will suggest a novel
      hypothesis for the pathogenic mechanism of PD that involves the lysosome and the
      different autophagy pathways. 

PMID- 26207398
TI  - Antimicrobial Pharmacokinetics and Pharmacodynamics.
AB  - BACKGROUND: Antimicrobial medications are beneficial when used appropriately, but
      adverse effects and resistance sometimes limit therapy. These effects may be more
      problematic with inappropriate antimicrobial use. Consideration of the
      pharmacokinetic and pharmacodynamic properties of these medications can help
      optimize drug use. METHODS: Review of the pertinent English-language literature.
      RESULTS: The pharmacokinetic principles of absorption, distribution, metabolism,
      and elimination determine whether an appropriate dose of medication reaches the
      intended pathogen. The pharmacodynamic properties of antimicrobial medications
      define the relation between the drug concentration and its observed effect on the
      target pathogen. Improvements in clinical outcomes have been observed when
      antimicrobial agents are dosed optimally according to these properties. In
      surgical patients, substantial changes in the volume of distribution and
      elimination necessitate a clear understanding of these principles. Additionally,
      less adverse drug effects and antimicrobial resistance may occur with optimal use
      of these drugs. CONCLUSION: Selecting and dosing antimicrobial medications with
      consideration of pharmacokinetics and pharmacodynamics may improve patient
      outcomes and avoid adverse effects.

PMID- 26207400
TI  - Efficacy and Safety of Ultrapure Alginate-Based Anti-Adhesion Gel in Experimental
      Peritonitis.
AB  - BACKGROUND: Intra-abdominal infection may lead to adhesion and abscess formation.
      An adhesion barrier can reduce these complications but also aggravate intra
      peritoneal infection, causing the opposite effects. The fear of infection
      propagation has limited clinical adhesion barrier use in a contaminated or
      infected abdomen. This study evaluated both adhesion and abscess reduction and
      infection propagation of a new ultrapure alginate-based anti-adhesive barrier gel
      in a rat peritonitis model. METHODS: In 64 male Wistar rats, bacterial
      peritonitis was induced via intra-abdominal injection of a mixture of sterile
      feces, 10(5) colony-forming units (CFU) of Escherichia coli, and 10(4) CFU of
      Bacteroides fragilis. Surgical debridement and peritoneal lavage were performed 1
      h after inoculation. Animals were randomly allocated in equal numbers to a
      control group or an alginate gel group. Animals were sacrificed on day five post
      operatively. Death and the presence and size of intra-abdominal abscesses were
      noted, and adhesions were scored. All outcomes were compared in the two groups.
      RESULTS: Seventeen rats (27%) died prematurely without any difference between the
      groups. Of the surviving rats in the alginate gel group, 88% developed abscesses
      vs. 100% of the control group. There was no significant difference in the abscess
      scores or incidence rates of adhesion formation between the groups. The adhesion
      scores were lower for the alginate gel group compared with control animals
      (p=0.04). CONCLUSION: Ultrapure alginate gel reduces adhesion severity but not
      abscesses. The gel seemed to be safe, not aggravating intra-peritoneal infection
      in this abdominal infection model.

PMID- 26207399
TI  - An Ounce of Prevention Saves Tons of Lives: Infection in Burns.
AB  - BACKGROUND: Modern day burn care continues to wage an uphill battle against an
      enemy that evolves faster than we can develop weapons. Bacteria (bioburden) are
      everywhere and can infiltrate anywhere within our susceptible population of burn
      patients. This is why prevention of infection is key to improving their survival
      and outcome. PURPOSE: To reduce the incidence of infection in the burn patient
      population. MATERIALS: Review of pertinent recent literature regarding infection
      prevention and control in the intensive care unit setting. RESULTS: We propose
      that bioburden is one of the central elements in the infectious cycle that is
      ever-present in burn units. The mechanism of bacterial entry into the unit and
      subsequent transmission and infection are delineated. Recommendations for
      mitigating this risk are provided to guide future clinicians in their care of
      burn patients. CONCLUSIONS: The treatment of infection and sepsis against highly
      adaptable bacteria is often insurmountable by ill patients. In this process,
      bioburden needs to be corralled to have any success. Thus, preventing organisms
      from entering the unit and transferring onto other patients, and eliminating the
      bacteria dwelling in the unit are all necessary actions in this battle.
      Ultimately, maintaining a culture that is constantly wary of this risk only can
      achieve this goal.

PMID- 26207401
TI  - Effectiveness of Prophylactic Antibiotics against Post-Ureteroscopic Lithotripsy
      Infections: Systematic Review and Meta-Analysis.
AB  - PURPOSE: To evaluate the effectiveness of prophylactic antibiotic therapy in
      reducing the incidence of post-ureteroscopic lithotripsy (URL) infections.
      METHODS: A systemic search of PubMED was performed to identify all randomized
      trials that compared the incidence of post-operative infections in patients
      without pre-operative urinary tract infections who underwent URL with and without
      a single dose of prophylactic antibiotics. The data were analyzed using Cochrane
      Collaboration Review Manager (RevMan, version 5.2). The endpoints of the analysis
      were pyuria (>10 white blood cells/high-power field), bacteriuria (urine culture
      with bacteria >10(5) colony-forming units/mL), and febrile urinary tract
      infections (fUTIs), defined as a body temperature of >38 degrees C with pyuria or
      meaningful bacteriuria within 1 wk after the operation. RESULTS: In total, four
      trials enrolling 500 patients met the inclusion criteria and were subjected to
      meta-analysis. Prophylactic antibiotics significantly reduced post-URL pyuria
      (risk ratios [RR] 0.65; 95% confidence interval [CI] 0.51-0.82) and bacteriuria
      (RR 0.26; 95% CI 0.12-0.60; p=0.001). Patients who received prophylactic
      antibiotics tended to have lower rates of fUTI, although the difference was not
      statistically significant. CONCLUSION: Prophylactic antibiotic therapy can reduce
      the incidence of pyuria and bacteriuria after URL. However, because of the low
      incidence of post-URL fUTIs, we failed to show that a single dose of prophylactic
      antibiotics can reduce the rate of such infections significantly.

PMID- 26207402
TI  - Clostridium difficile Infections after Blunt Trauma: A Different Patient
      Population?
AB  - BACKGROUND: The epidemiology of Clostridium difficile-associated infection (CDI)
      has changed, and it is evident that susceptibility is related not only to
      exposures and bacterial potency, but host factors as well. Several small studies
      have suggested that CDI after trauma is associated with a different patient
      phenotype. The purpose of this study was to examine and describe the
      epidemiologic factors associated with C. difficile in blunt trauma patients
      without traumatic brain injury using the Trauma-Related Database as a part of the
      "Inflammation and Host Response to Injury" (Glue Grant) and the University of
      Florida Integrated Data Repository. METHODS: Previously recorded baseline
      characteristics, clinical data, and outcomes were compared between groups (67 C.
      difficile and 384 uncomplicated, 813 intermediate, and 761 complicated non-C.
      difficile patients) as defined by the Glue Grant on admission and at days seven
      and 14. RESULTS: The majority of CDI patients experienced complicated or
      intermediate clinical courses. The mean ages of all cohorts were less than 65 y
      and CDI patients were significantly older than uncomplicated patients without
      CDI. The CDI patients had increased days in the hospital and on the ventilator,
      as well as significantly higher new injury severity scores (NISS), and a greater
      percentage of patients with NISS >34 points compared with non-CDI patients. They
      also had greater Marshall and Denver multiple organ dysfunction scores than non
      CDI uncomplicated patients, and greater creatinine, alkaline phosphatase,
      neutrophil count, lactic acid, and PiO2:FiO2 compared with all non-CDI cohorts on
      admission. In addition, the CDI patients had higher glucose concentrations and
      base deficit from uncomplicated patients and greater leukocytosis than
      complicated patients on admission. Several of these changes persisted to days
      seven and 14. CONCLUSION: Analysis of severe blunt trauma patients with C.
      difficile, as compared with non-CDI patients, reveals evidence of increased
      inflammation, immunosuppression, worse acute kidney injury, higher NISS, greater
      days in the hospital and on the ventilator, higher organ injury scores, and
      prolonged clinical courses. This supports reports of an increased prevalence of
      CDI in a younger population not believed previously to be at risk. This unique
      population may have specific genomic or inflammation-related risk factors that
      may play more important roles in disease susceptibility. Prospective analysis may
      allow early identification of at-risk patients, creation of novel therapeutics,
      and improved understanding of how and why C. difficile colonization transforms
      into infection after severe blunt trauma.

PMID- 26207403
TI  - Hospital Cost of Staphylococcal Infection after Cardiothoracic or Orthopedic
      Operations in France: A Retrospective Database Analysis.
AB  - BACKGROUND: Staphylococcal infections (SI) after cardiothoracic (CT) or
      orthopedic (OP) surgery are associated with extended length of stay (LOS), a
      considerable mortality rate, and high cost. No data on these consequences have
      been published in France. Therefore, a study was conducted to describe the
      epidemiologic, clinical, and economic outcomes of SI following these operations
      in France based on a hospital discharge database. METHODS: Patients who underwent
      the most common types of CT or OP operations in 2009 were identified and followed
      for one year. Staphylococcal infections occurring in the three following months
      were identified. RESULTS: In 2009, 21,543 patients underwent one of the selected
      CT procedures (62% coronary artery bypass grafting; 38% cardiac valve
      replacement) and 175,518 patients underwent one of the selected OP procedures
      (64% hip arthroplasty; 36% knee arthroplasty). Among the patients, 4.4% (n=955)
      and 0.9% (n=1,515) developed SI after CT and OP surgery, respectively.
      Staphylococcal infection led to approximately 1.0 and 1.4 additional
      hospitalizations per patient, 22.1 and 24.1 additional hospital days, and an
      excess cost of ?15,475 and ?13,389 after an CT or OP procedure, respectively. The
      in-hospital mortality rate was 2.6 times and 6 times greater in infected patients
      than in non-infected patients for CT and OP. Hospital cost reached ?505 million
      for these two CT procedures and ?1.9 billion for the two OP procedures, of which
      ?15 million and ?20 million were related directly to patients having developed
      SI. CONCLUSIONS: Staphylococcal infections after common CT or OP operations were
      associated with greater mortality rates and hospital costs secondary to the
      additional procedures and greater LOS.

PMID- 26207404
TI  - ?

PMID- 26207405
TI  - ?

PMID- 26207407
TI  - ?

PMID- 26207406
TI  - ?

PMID- 26207408
TI  - ?

PMID- 26207409
TI  - Epidemiology, microbiology, and antibiotic susceptibility patterns of skin and
      soft tissue infections, Joint Base San Antonio-Lackland, Texas, 2012-2014.
AB  - Skin and soft tissue infections (SSTIs), including those caused by methicillin
      resistant Staphylococcus aureus (MRSA), are common in military training
      environments. In 2014, the healthcare providers for trainees at Joint Base San
      Antonio (JBSA)-Lackland, TX, notified the surveillance unit of increased
      antibiotic resistance reported on wound cultures of purulent SSTIs. To provide
      updated clinical guidance to local providers, the surveillance unit conducted a
      review of all SSTIs diagnosed among trainees at JBSA-Lackland between 1 October
      2012 and 31 December 2014. SSTI cumulative incidence during the surveillance
      period was 0.81%, with similar rates between males (0.80%) and females (0.84%)
      and between basic (0.82%) and technical (0.79%) trainees. Of 772 total cases, 254
      were cultured; 196 resulted in growth of one or more pathogens: MRSA (n=110);
      methicillin-sensitive S. aureus (n=68); other gram-positive cocci (n=5); and gram
      negative rods (n=18). In vitro activity of commonly used antibiotics against S.
      aureus isolates dropped slightly from the previous surveillance period. In
      addition to novel antibiotic research and development, these trends warrant
      enhanced local preventive efforts and close adherence to evidence-based treatment
      algorithms. 

PMID- 26207410
TI  - Post-deployment screening and referral for risky alcohol use and subsequent
      alcohol-related and injury diagnoses, active component, U.S. Armed Forces, 2008
      2014.
AB  - Risky alcohol use among service members is a threat to both military readiness
      and the health of service members. This report describes an analysis using the
      Defense Medical Surveillance System (DMSS) to identify all active component
      service members who returned from deployment and completed the Alcohol Use
      Disorders Identification Test-Consumption (AUDIT-C) alcohol use screen as part of
      the Post Deployment Health Assessment (PDHA) and Post Deployment Health
      Reassessment (PDHRA) during 2008-2014. This analysis identified that 3.4% of PDHA
      forms and 4.8% of PDHRA forms completed indicated severe risk for alcohol abuse,
      defined as an AUDIT-C score of 8 or higher. Among those at severe risk on the
      PDHRA who were not already under care for alcohol abuse, only 37.7% received a
      referral for treatment: 21.7% to primary care, 13.4% to behavioral health in
      primary care, 7.5% to mental health specialty care, and 5.6% to a substance abuse
      program. Referrals for treatment for those at severe risk were lower than their
      respective counterparts among males, white non-Hispanics, members of the Air
      Force, junior officers, and pilots/air crew. There were significant trends of
      increasing frequencies of subsequent injury and alcohol-related conditions as
      alcohol use levels increased. 

PMID- 26207411
TI  - Incidence of gastroesophageal reflux disease (GERD), active component, U.S. Armed
      Forces, 2005-2014.
AB  - Gastroesophageal reflux disease (GERD) is a common condition among adults that
      can cause symptoms such as frequent heartburn, substernal chest pain, and
      regurgitation of food. During 2005-2014, a total of 137,081 active component
      service members had an incident (first-ever) diagnosis of GERD (incidence rate:
      101.3 per 10,000 person-years). Incidence rates were higher than their respective
      counterparts among females, black and white non-Hispanics, service members in the
      Coast Guard and Air Force, officers, and those in healthcare occupations. Rates
      increased monotonically with increasing age groups. Most GERD cases (79.2%) were
      uncomplicated GERD; however, 20.8% were identified as having a symptom or
      complication linked to their GERD diagnosis. Lifestyle changes, medication, and
      prevention of serious complications should be emphasized among individuals
      diagnosed with GERD, particularly those at risk for severe disease. 

PMID- 26207412
TI  - Surveillance snapshot: Prevalence of antibodies to viral causes of vaccine
      preventable illnesses by state home of record among Air Force recruits, 25 April
      2013-24 April 2014.

PMID- 26207413
TI  - Synthesis of Hemoglobin Conjugated Polymeric Micelle: A ZnPc Carrier with Oxygen
      Self-Compensating Ability for Photodynamic Therapy.
AB  - Photodynamic therapy (PDT) is a promising singlet oxygen ((1)O2) mediated
      clinical treatment for many tumors. As the source of (1)O2, oxygen plays an
      important role in the curative effect of PDT. However, the facts of photochemical
      depletion of oxygen and the intrinsic hypoxic microenvironment of tumors remain
      the major challenges. In this work, a novel photosensitizer carrier with oxygen
      self-compensating ability was designed for PDT. It was synthesized via chemical
      conjugation of hemoglobin (Hb) to polymeric micelles formed by triblock
      copolymers of poly(ethylene glycol)-block-poly(acrylic acid)-block-polystyrene
      (PEG-b-PAA-b-PS). The PEG-b-PAA-b-PS and resultant micelles in aqueous solution
      were comprehensively characterized by means of FTIR, (1)H NMR, GPC, DLS, TEM, and
      fluorescence spectroscopy. The oxygen-binding capacity and antioxidative activity
      of the Hb conjugated micelles were evaluated via UV-vis spectroscopy. In
      addition, compared with the control micelles without Hb, the Hb conjugated
      photosensitizer carrier was able to generate more (1)O2 and exert greater
      photocytotoxicity on Hela cells in vitro. 

PMID- 26207414
TI  - Intramolecular didehydro-Diels-Alder reaction and its impact on the structure
      function properties of environmentally sensitive fluorophores.
AB  - Reaction discovery plays a vital role in accessing new chemical entities and
      materials possessing important function.1 In this Account, we delineate our
      reaction discovery program regarding the [4 + 2] cycloaddition reaction of
      styrene-ynes. In particular, we highlight our studies that lead to the
      realization of the diverging reaction mechanisms of the intramolecular didehydro
      Diels-Alder (IMDDA) reaction to afford dihydronaphthalene and naphthalene
      products. Formation of the former involves an intermolecular hydrogen atom
      abstraction and isomerization, whereas the latter is formed via an unexpected
      elimination of H2. Forming aromatic compounds by a unimolecular elimination of H2
      offers an environmentally benign alternative to typical oxidation protocols. We
      also include in this Account ongoing work focused on expanding the scope of this
      reaction, mainly its application to the preparation of cyclopenta[b]naphthalenes.
      Finally, we showcase the synthetic utility of the IMDDA reaction by preparing
      novel environmentally sensitive fluorophores. The choice to follow this path was
      largely influenced by the impact this reaction could have on our understanding of
      the structure-function relationships of these molecular sensors by taking
      advantage of a de novo construction and functionalization of the aromatic portion
      of these compounds. We were also inspired by the fact that, despite the advances
      that have been made in the construction of small molecule fluorophores, access to
      rationally designed fluorescent probes or sensors possessing varied and tuned
      photophysical, spectral, and chemical properties are still needed. To this end,
      we report our studies to correlate fluorophore structure with photophysical
      property relationships for a series of solvatochromic PRODAN analogs and
      viscosity-sensitive cyanoacrylate analogs. The versatility of this de novo
      strategy for fluorophore synthesis was demonstrated by showing that a number of
      functional groups could be installed at various locations, including handles for
      eventual biomolecule attachment or water-solubilizing groups. Further, biothiol
      sensors were designed, and we expect these to be of general utility for the study
      of lipid dynamics in cellular membranes and for the detection of protein-binding
      interactions, ideal applications for these relatively hydrophobic fluorophores.
      Future studies will be directed toward expanding this chemistry-driven approach
      to the rational preparation of fluorophores with enhanced photophysical and
      chemical properties for application in biological systems. 

PMID- 26207415
TI  - Resting state glutamate predicts elevated pre-stimulus alpha during self
      relatedness: A combined EEG-MRS study on "rest-self overlap".
AB  - Recent studies have demonstrated neural overlap between resting state activity
      and self-referential processing. This "rest-self" overlap occurs especially in
      anterior cortical midline structures like the perigenual anterior cingulate
      cortex (PACC). However, the exact neurotemporal and biochemical mechanisms remain
      to be identified. Therefore, we conducted a combined electroencephalography (EEG)
      magnetic resonance spectroscopy (MRS) study. EEG focused on pre-stimulus (e.g.,
      prior to stimulus presentation or perception) power changes to assess the degree
      to which those changes can predict subjects' perception (and judgment) of
      subsequent stimuli as high or low self-related. MRS measured resting state
      concentration of glutamate, focusing on PACC. High pre-stimulus (e.g., prior to
      stimulus presentation or perception) alpha power significantly correlated with
      both perception of stimuli judged to be highly self-related and with resting
      state glutamate concentrations in the PACC. In sum, our results show (i) pre
      stimulus (e.g., prior to stimulus presentation or perception) alpha power and
      resting state glutamate concentration to mediate rest-self overlap that (ii)
      dispose or incline subjects to assign high degrees of self-relatedness to
      perceptual stimuli. 

PMID- 26207416
TI  - Outcomes from personal budgets in mental health: service users' experiences in
      three English local authorities.
AB  - BACKGROUND: In England, personal budgets are offered to eligible people with
      severe mental health problems to enable them to purchase what is helpful for
      their quality of life or recovery. However, in-depth insight into people's own
      perceptions of the outcomes is lacking. AIMS: To investigate people's own
      reporting of outcomes from using personal budgets in relation to social care
      needs arising from severe mental health problems. METHOD: A convenience sample of
      47 individuals receiving personal budgets was recruited from three English local
      authorities. In-depth semi-structured interviews were subject to thematic
      framework analysis. RESULTS: Most participants identified positive outcomes
      across domains interconnected through individual life circumstances, with mental
      health and wellbeing, social participation and relationships, and confidence and
      skills most commonly reported. Some needed more support than others to identify
      goals and make use of the personal budget to take a more active part in the
      society. CONCLUSIONS: Personal budgets can enable people to achieve outcomes that
      are relevant to them in the context of their lives, particularly through
      enhancing their wellbeing and social participation. Consideration should be given
      to distinguishing those individuals potentially requiring more support for
      engagement from those who can engage more independently to identify and pursue
      their goals.

PMID- 26207417
TI  - CT-Based Determination of Ureteral Stone Volume: A Predictor of Spontaneous
      Passage.
AB  - INTRODUCTION AND OBJECTIVES: Which ureteral stone can pass spontaneously? It is
      hard to answer this question exactly. The size and location of the stone are the
      most important predictors. However, there is still a considerable gray zone that
      needs to be clarified. We try to identify the role of stone volume (SV) in the
      prediction of spontaneous passage (SP). MATERIALS AND METHODS: Seventy-eight
      patients with a solitary ureteral stone were retrospectively evaluated. Ureter SV
      measurements were taken in three planes and were calculated using the following
      formula: V = (X) * (Y) * (Z) * 0.52. SVs, and the longest diameters (LDs) were
      compared between patients who passed stones spontaneously and those who needed
      intervention. RESULTS: The SVs and LDs were significantly lower in patients who
      passed stones spontaneously than in patients who required intervention (41.2 +/-
      35.5 vs 128.1 +/- 91.1 mm(3), p = 0.001; 5.7 +/- 1.8 vs 7.4 +/- 1.7 mm, p =
      0.001). The optimum cutoff values were 7.0 mm and 52.6 mm(3) for the LD and SV,
      respectively. For those stones of <=7 mm, the volumes of the stones that could
      and could not pass did not differ significantly. However, the volume of the
      stones >7.0 mm that could pass was significantly higher than of those that could
      not. SP was 30.6% for stones >7 mm; however, when we removed the stones >52.6
      mm(3), SP increased to 75% for stones higher than 7 mm (p = 0.001). CONCLUSIONS:
      To classify ureteral stones using only one parameter such as stone diameter may
      lead to heterogeneity within the group. SV may be used in addition to size to
      determine a more definite homogeneous group to predict SP more precisely.

PMID- 26207418
TI  - Phosphoric Acid-Mediated Synthesis of Vinyl Sulfones through Decarboxylative
      Coupling Reactions of Sodium Sulfinates with Phenylpropiolic Acids.
AB  - A novel phosphoric acid -mediated synthesis of vinyl sulfones through
      decarboxylative coupling reactions of sodium sulfinates with phenylpropiolic
      acids is described. This transformation is efficient and environmentally
      friendly. 

PMID- 26207419
TI  - Comparison of three formal methods used to estimate the functional axis of
      rotation: an extensive in-vivo analysis performed on the knee joint.
AB  - Estimating the main axis of rotation (AoR) of a human joint represents an
      important issue in biomechanics. This study compared three formal methods used to
      estimate functional AoR, namely a cylindrical fitting method, a mean helical axis
      transformation, and a symmetrical axis approach. These methods were tested on 106
      subjects undergoing navigated total knee arthroplasty. AoR orientation in 3D and
      in the frontal and coronal planes provided by each method was compared to the
      transepicondylar axis direction. Although all the methods resulted effective,
      significant differences were identified among them, relatively to the orientation
      in 3D and in the frontal plane projection. This was probably due to the presence
      of secondary rotations during the first degrees of knee flexion. 

PMID- 26207423
TI  - Candida glabrata--unique features and challenges in the clinical management of
      invasive infections.
AB  - Candida glabrata is a pathogenic yeast with several unique biological features.
      This article provides an up-to-date review on current data and reasoning aspects
      of this clinically problematic organism. Haploidy, absence of pseudohyphae,
      facultative anaerobe growth of C. glabrata, as well as its intrinsically low
      susceptibility to azole antifungals require specific consideration in diagnosis
      and treatment approaches. As C. glabrata today represents a sizeable percentage
      of pathogens in candidaemia, the use of azole antifungals in upfront therapy of
      invasive yeast infections is discouraged by recent guidelines. While the
      selection of C. glabrata mutants with impaired susceptibility to echinocandins
      has been described, analyses of several clinical studies indicate an association
      of improved outcomes with the use of echinocandins as the primary treatment for
      invasive yeast infections with potential or documented involvement of C.
      glabrata. 

PMID- 26207422
TI  - Functional Roles of N-Linked Glycosylation of Human Matrix Metalloproteinase 9.
AB  - Matrix metalloproteinase-9 (MMP-9) is a secreted endoproteinase with a critical
      role in the regulation of the extracellular matrix and proteolytic activation of
      signaling molecules. Human (h)MMP-9 has two well-defined N-glycosylation sites at
      residues N38 and N120; however, their role has remained mostly unexplored partly
      because expression of the N-glycosylation-deficient N38S has been difficult due
      to a recently discovered single nucleotide polymorphism-dependent miRNA-mediated
      inhibitory mechanism. hMMP-9 cDNA encoding amino acid substitutions at residues
      38 (modified-S38, mS38) or 120 (N120S) were created in the background of a miRNA
      binding site disrupted template and expressed by transient transfection. hMMP-9
      harboring a single mS38 replacement secreted well, whereas N120S, or a double
      mS38/N120S hMMP-9 demonstrated much reduced secretion. Imaging indicated
      endoplasmic reticulum (ER) retention of the non-secreted variants and co
      immunoprecipitation confirmed an enhanced strong interaction between the non
      secreted hMMP-9 and the ER-resident protein calreticulin (CALR). Removal of N
      glycosylation at residue 38 revealed an amino acid-dependent strong interaction
      with CALR likely preventing unloading of the misfolded protein from the ER
      chaperone down the normal secretory pathway. As with other glycoproteins, N
      glycosylation strongly regulates hMMP-9 secretion. This is mediated, however,
      through a novel mechanism of cloaking an N-glycosylation-independent strong
      interaction with the ER-resident CALR. 

PMID- 26207424
TI  - The Role of miR-212 and iNOS in Alcohol-Induced Intestinal Barrier Dysfunction
      and Steatohepatitis.
AB  - BACKGROUND: Alcoholic liver disease is commonly associated with intestinal
      barrier dysfunction. Alcohol-induced dysregulation of intestinal tight junction
      proteins, such as Zonula Occludens-1 (ZO-1), plays an important role in alcohol
      induced gut leakiness. However, the mechanism of alcohol-induced disruption of
      tight junction proteins is not well established. The goal of this study was to
      elucidate this mechanism by studying the role of microRNA 212 (miR-212) and
      inducible nitric oxide synthase (iNOS) in alcohol-induced gut leakiness. METHODS:
      The permeability of the Caco-2 monolayer was assessed by transepithelial
      electrical resistance and flux of fluorescein sulfonic acid. miR-212 was measured
      by real-time polymerase chain reaction. The wild-type, iNOS knockout, and miR-212
      knockdown mice were fed with alcohol diet (29% of total calories, 4.5% v/v) for 8
      weeks. The LNA-anti-miR-212 was used to inhibit miR-212 expression in mice. The
      alcohol-induced intestinal permeability, miR-212 expression, and liver injuries
      in mice were measured. RESULTS: Our in vitro monolayer and in vivo mice studies
      showed that: (i) alcohol-induced overexpression of the intestinal miR-212 and
      intestinal hyperpermeability is prevented using miR-212 knockdown techniques; and
      (ii) iNOS is up-regulated in the intestine by alcohol and that iNOS signaling is
      required for alcohol-induced miR-212 overexpression, ZO-1 disruption, gut
      leakiness, and steatohepatitis. CONCLUSIONS: These studies thus support a novel
      miR-212 mechanism for alcohol-induced gut leakiness and a potential target that
      could be exploited for therapeutic intervention to prevent leaky gut and liver
      injury in alcoholics.

PMID- 26207426
TI  - Reply: To PMID 26203758.

PMID- 26207425
TI  - Brief Exercises Affect Gene Expression in Circulating Monocytes.
AB  - We aimed to give a systematic hypothesis on the functions of exercise on
      circulating monocytes by identifying a discrete set of genes in circulating
      monocytes that were altered by exercise. The microarray expression profile of
      GSE51835 was downloaded from gene expression omnibus (GEO) database for the
      identification of differentially expressed genes (DEGs) using limma and affy
      packages in R language. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes
      and Genomes (KEGG) pathway analysis were performed for DEGs, followed by the
      construction of co-expression network and protein-protein interaction (PPI)
      network. The top 10 nodes in PPI network were screened, and subnetwork was
      constructed for the key genes identification. Totally, 35 DEGs, including 2
      upregulated genes and 33 downregulated genes, were identified. The enriched GO
      terms were mainly linked to immune response and defence response, and the
      enriched KEGG pathways were mainly associated with natural killer cell-mediated
      cytotoxicity and graft-versus-host disease. Dual-specificity phosphatase 2
      (DUSP2) was identified as a key node in the co-expression network. In the PPI
      network, CD247 module (CD247), chemokine (C-X-C motif) receptor 4 (CXCR4),
      granzyme B (GZMB) and perforin 1 (PRF1) were identified as key nodes. An
      important interaction, GZMB/PRF1, was detected. Five key genes, including DUSP2,
      CD247, CXCR4, GZMB and PRF1, and an interaction of GZMB/PRF1, were significant
      factors in the immune processes of circulating monocytes, which might be
      regulated by brief exercises, leading to the enhancement of immune function.

PMID- 26207428
TI  - Abiraterone in heavily pretreated patients with metastatic castrate-resistant
      prostate cancer: final analysis of overall survival.

PMID- 26207427
TI  - Formation of Low Volatility Organic Compounds and Secondary Organic Aerosol from
      Isoprene Hydroxyhydroperoxide Low-NO Oxidation.
AB  - Gas-phase low volatility organic compounds (LVOC), produced from oxidation of
      isoprene 4-hydroxy-3-hydroperoxide (4,3-ISOPOOH) under low-NO conditions, were
      observed during the FIXCIT chamber study. Decreases in LVOC directly correspond
      to appearance and growth in secondary organic aerosol (SOA) of consistent
      elemental composition, indicating that LVOC condense (at OA below 1 MUg m(-3)).
      This represents the first simultaneous measurement of condensing low volatility
      species from isoprene oxidation in both the gas and particle phases. The SOA
      formation in this study is separate from previously described isoprene epoxydiol
      (IEPOX) uptake. Assigning all condensing LVOC signals to 4,3-ISOPOOH oxidation in
      the chamber study implies a wall-loss corrected non-IEPOX SOA mass yield of ~4%.
      By contrast to monoterpene oxidation, in which extremely low volatility VOC
      (ELVOC) constitute the organic aerosol, in the isoprene system LVOC with
      saturation concentrations from 10(-2) to 10 MUg m(-3) are the main constituents.
      These LVOC may be important for the growth of nanoparticles in environments with
      low OA concentrations. LVOC observed in the chamber were also observed in the
      atmosphere during SOAS-2013 in the Southeastern United States, with the expected
      diurnal cycle. This previously uncharacterized aerosol formation pathway could
      account for ~5.0 Tg yr(-1) of SOA production, or 3.3% of global SOA. 

PMID- 26207430
TI  - Risk determination method for accidental water basin contamination based on risk
      source coupling with sensitive targets.
AB  - Accidental water basin pollution seriously threatens human health and ecological
      security, but rapid, effective methods for evaluating this threat are lacking.
      This paper aims to develop a risk evaluation method for basin accidents by
      coupling the risk source with sensitive targets to evaluate the zone accident
      risk levels of basins and prevent the accidental environmental pollution of
      water. This method incorporates the interplay between risk sources and sensitive
      targets by evaluating the zone risk levels of water environments from different
      sources, effectiveness of the risk source control mechanisms, vulnerability of
      sensitive targets and spatial and temporal relationships between these sources
      and targets. Using the Three Gorges Reservoir region as an example, a risk system
      for water basin pollution incidents consisting of a risk indicator quantification
      system, a risk zoning method and a verification method for the zoning results is
      developed and implemented. The results were verified in a field investigation,
      which showed that the risk zoning model provides rapid, effective and reliable
      zoning results. This research method could serve as a theoretical reference and
      technological support for evaluating water basin accident risks. Furthermore, the
      results are useful for evaluating and protecting the aquatic environments in the
      Three Gorges Reservoir region. 

PMID- 26207429
TI  - Finite Element Analysis of Bone Stress for Miniscrew Implant Proximal to Root
      Under Occlusal Force and Implant Loading.
AB  - Because of the narrow interradicular spaces and varying oral anatomies of
      individual patients, there is a very high risk of root proximity during the mini
      implants inserting. The authors hypothesized that normal occlusal loading and
      implant loading affected the stability of miniscrew implants placed in proximity
      or contact with the adjacent root. The authors implemented finite element
      analysis (FEA) to examine the effectiveness of root proximity and root contact.
      Stress distribution in the bone was assessed at different degrees of root
      proximity by generating 4 finite element models: the implant touches the root
      surface, the implant was embedded in the periodontal membrane, the implant
      touches the periodontal surface, and the implant touches nothing. Finite element
      analysis was then carried out with simulations of 2 loading conditions for each
      model: condition A, involving only tooth loading and condition B, involving both
      tooth and implant loading. Under loading condition A, the maximum stress on the
      bone for the implant touching the root was the distinctly higher than that for
      the other models. For loading condition B, peak stress areas for the implant
      touching the root were the area around the neck of the mini implant and the point
      of the mini implant touches the root. The results of this study suggest that
      normal occlusal loading and implant loading contribute to the instability of the
      mini implant when the mini implant touches the root. 

PMID- 26207431
TI  - Neuraxial anesthesia for pain control after cesarean section: a prospective
      randomized trial comparing three different neuraxial techniques in clinical
      practice.
AB  - BACKGROUND: Cesarean section (CS) is associated with a moderate-high intensity of
      postoperative pain. We investigate whether continuous local anesthetic/opioid
      administration using patient controlled epidural anesthesia (PCEA) is superior in
      controlling pain after CS than epidural (ED) or intrathecal (IT) opioid bolus
      administration. METHODS: One hundred ninety-nine women undergoing elective CS
      were randomized into 3 groups: PCEA: Combined spinal-epidural anesthesia (CSE)
      with a PCEA of ropivacaine 0.1% + sufentanil 0.5 MUg/mL for 24 hours after CS.
      ED: CSE with an ED bolus of 3 mg morphine after CS. IT: spinal anesthesia with an
      IT bolus of 0.1 mg morphine before CS. Primary objectives were pain (VAS/Visual
      Analogue Scale 0-100) at 9 h, VAS at 1, 2, 6, 24 and 48 hours, side effects and
      additional analgesic requirements as secondary endpoints. RESULTS: VAS
      (rest/mobilization) 10(0-23)/40(20-56) at 9 hours for IT was lower
      (P=0.11/P=0.003) than VAS 20(0-30)/50(30-60) for ED and 20(0-40)/50(30-70) for
      PCEA (P=0.005/P=0.01). VAS 10(0-29)/40(20-60) at 6 hours for IT was significantly
      lower than VAS 20(4-40)/50(30-70) for ED (P=0.02/P=0.02). During mobilization at
      24/48 hours VAS 40(20-58)/30(20-40) between IT and PCEA with VAS 50(40-70)/40(20
      63) differed significantly (P=0.04/P=0.001). With exception of pruritus, which
      was less in the PCEA group at 9 hours, side effects were similar in all groups.
      Ibuprofen consumption in the first 24 hours was significantly lower for IT and
      PCEA compared to ED. CONCLUSIONS: PCEA is less effective then IT and ED opioid
      bolus administration for post cesarean pain relief. IT provides better analgesia
      than ED or PCEA, as pointed out by lower ibuprofen consumption.

PMID- 26207432
TI  - A new strategy to deliver Helmet CPAP to critically ill patients: the possible
      role of ICU ventilators.

PMID- 26207433
TI  - Is the reduction of 0.9% saline use in Italian Intensive Care Units feasible?

PMID- 26207435
TI  - Characterization of midazolam metabolism in locusts: the role of a CYP3A4-like
      enzyme in the formation of 1'-OH and 4-OH midazolam.
AB  - 1. The metabolism of midazolam was investigated in vivo in locusts in order to
      evaluate the presence of an enzyme with functionality similar to human CYP3A4/5.
      2. Hydroxylated metabolites of midazolam identical to human metabolites were
      detected in locusts and the apparent affinities (Km values) were in the same
      range as reported in humans (in locusts: 7-23 and 33-85 uM for the formation of
      the 1'-OH and 4-OH metabolites, respectively). 3. The formation of hydroxylated
      metabolites could successfully be inhibited by co-administration of ketoconazole,
      a known CYP3A4/5 inhibitor. 4. Besides phase I metabolites, a number of
      conjugated metabolites were detected using high-resolution mass spectrometry. The
      most abundant metabolites detected were structurally identified by (1)H NMR as
      two N-glucosides. NMR analysis strongly suggested that the glycosylation occurred
      at the two nitrogens (either one in each case) of the imidazole ring. 5.
      Distribution of midazolam and the glucose conjugates were successfully measured
      using desorption electrospray mass spectrometry imaging revealing time-dependent
      changes in distribution over time. 6. In conclusion, it appears that an enzyme
      with functionality similar to human CYP3A4/5 is present in locusts. However, it
      appears that conjugation with glucose is the main detoxification pathway of
      midazolam in locusts. 

PMID- 26207436
TI  - Unusual Differentiation to Pheochromocytoma-Like Cells in an Adrenal
      Neuroblastoma After Chemotherapy: A Case Report and Literature Review.
AB  - The authors present a case of 3-year-old female with Stage 4 neuroblastoma
      originating from the left adrenal gland. Biopsy of the left adrenal tumor showed
      neuroblastoma. After three courses of chemotherapy, the left adrenal gland
      including the left adrenal tumor was surgically removed. Pathological findings of
      the resected tumor revealed that most of the neuroblastoma tissues changed to
      pheochromocytoma-like cells. The tumor cells were arranged in well-defined nests
      surrounded by a delicate fibrovascular stroma and had granular eosinophilic
      cytoplasm, and round to oval nuclei. Immunohistological analysis of the biopsy
      samples showed strongly positive Ganglioside GD2-staining cells, whereas almost
      all of the tumor cells in the resected specimen were Ganglioside GD2-negative;
      cells were very weakly stained. The authors suggest that a part of the
      neuroblastoma in the left adrenal gland exhibited unusual differentiation toward
      pheochromocytic lineage Ganglioside GD2-negative neuroblastoma in a patient who
      had been treated with intensive chemotherapy.

PMID- 26207437
TI  - Plasmid-Mediated Quinolone Resistance in Escherichia coli Isolates from Wild
      Birds and Chickens in South Korea.
AB  - A total of 2,423 nonduplicate isolates of Escherichia coli recovered from wild
      birds (n=793) and chickens (n=1,630) in South Korea were investigated for plasmid
      mediated quinolone resistance (PMQR) genes. Altogether, 56 isolates with PMQR
      genes were identified, including 25 (3.2%) from wild birds and 31 (1.9%) from
      chickens, which were further characterized using molecular methods. Among them,
      qnrS, aac(6')-Ib-cr, qnrB, and qepA genes were detected in 47 (1.9%), 6 (0.24%),
      2 (0.08%), and 1 (0.04%) isolates, respectively. The most prevalent gene, qnrS,
      was identified in 21 (0.9%) and 26 (1.1%) isolates from wild birds and chickens,
      respectively. The qnrB gene was identified in two chicken isolates, which
      included qnrB19 and a novel qnrB44 gene. Plasmid isolation and Southern
      hybridization revealed that qnrS1 was located on a large (>200 kbp) plasmid. The
      spread of the PMQR genes was attributed to a combination of horizontal
      dissemination and clonal expansion. The horizontal dissemination of PMQR genes
      was mostly mediated by IncK plasmids. Molecular typing demonstrated that the
      majority of the PMQR-positive isolates were genetically diverse. Only one chicken
      isolate belonged to ST131, which harbored an additional CMY-2 gene. Our findings
      suggest that the wild birds could serve as reservoirs of PMQR genes and spread
      them over long distances through migration. To our knowledge, this is the first
      report of PMQR genes in Korean wild birds. This study also reports qnrS2, qnrB19,
      qnrB44, and qepA genes for the first time in animal E. coli isolates from South
      Korea. 

PMID- 26207438
TI  - Responding to a suicidal friend or family member: A qualitative study of college
      students.
AB  - The purpose of this qualitative study was to understand how college students have
      responded, at any point in their lifetime, to a suicidal friend or family member.
      College students completed an online survey in which they described, in their own
      words, what they have done when a friend or family member disclosed being
      suicidal. These responses included providing social support, information, telling
      someone, and crisis support. Future studies are needed to determine how common
      these responses are, identify factors that predict certain responses, and examine
      the impact responding to a suicidal person can have on college student wellbeing.

PMID- 26207439
TI  - Patient-Reported Outcomes in Male and Female Collegiate Soccer Players During an
      Athletic Season.
AB  - CONTEXT: Clinicians are urged to document patient-based outcomes during
      rehabilitation to measure health-related quality of life (HRQOL) from the
      patient's perspective. It is unclear how scores on patient-reported outcome
      instruments (PROs) vary over the course of an athletic season because of normal
      athletic participation. OBJECTIVE: Our primary purpose was to evaluate the effect
      of administration time point on HRQOL during an athletic season. Secondary
      purposes were to determine test-retest reliability and minimal detectable change
      scores of 3 PROs commonly used in clinical practice and if a relationship exists
      between generic and region-specific outcome instruments. DESIGN: Cross-sectional
      study. SETTING: Athletic facility. PATIENTS OR OTHER PARTICIPANTS: Twenty-three
      collegiate soccer athletes (11 men, 12 women). MAIN OUTCOME MEASURE(S): At 5 time
      points over a spring season, we administered the Disablement in the Physically
      Active Scale (DPA), Foot and Ankle Ability Measure-Sport, and Knee Injury and
      Osteoarthritis Outcome Score (KOOS). RESULTS: Time effects were observed for the
      DPA (P = .011) and KOOS Quality of Life subscale (P = .027). However, the
      differences between individual time points did not surpass the minimal detectable
      change for the DPA, and no post hoc analyses were significant for the KOOS
      Quality of Life subscale. Test-retest reliability was moderate for the KOOS-Pain
      subscale (intraclass correlation coefficient = 0.71) and good for the remaining
      KOOS subscales, DPA, and Foot and Ankle Ability Measure-Sport (intraclass
      correlation coefficients > 0.79). The DPA and KOOS-Sport subscale demonstrated a
      significant moderate relationship (P = .018). CONCLUSIONS: Athletic participation
      during a nontraditional, spring soccer season did not affect HRQOL. All 3 PROs
      were reliable and could be used clinically to monitor changes in health status
      throughout an athletic season. Our results demonstrate that significant
      deviations in scores were related to factors other than participation, such as
      injury. Finally, both generic and region-specific instruments should be used in
      clinical practice.

PMID- 26207441
TI  - ?

PMID- 26207442
TI  - ?

PMID- 26207440
TI  - Pressure on Sports Medicine Clinicians to Prematurely Return Collegiate Athletes
      to Play After Concussion.
AB  - CONTEXT: Anecdotal and qualitative evidence has suggested that some clinicians
      face pressure from coaches and other personnel in the athletic environment to
      prematurely return athletes to participation after a concussion. This type of
      pressure potentially can result in compromised patient care. OBJECTIVE: To
      quantify the extent to which clinicians in the collegiate sports medicine
      environment experience pressure when caring for concussed athletes and whether
      this pressure varies by the supervisory structure of the institution's sports
      medicine department, the clinician's sex, and other factors. DESIGN: Cross
      sectional study. SETTING: Web-based survey of National College Athletic
      Association member institutions. PATIENTS OR OTHER PARTICIPANTS: A total of 789
      athletic trainers and 111 team physicians from 530 institutions. MAIN OUTCOME
      MEASURE(S): We asked participants whether they had experienced pressure from 3
      stakeholder populations (other clinicians, coaches, athletes) to prematurely
      return athletes to participation after a concussion. Modifying variables that we
      assessed were the position (athletic trainer, physician) and sex of the
      clinicians, the supervisory structure of their institutions' sports medicine
      departments, and the division of competition in which their institutions
      participate. RESULTS: We observed that 64.4% (n = 580) of responding clinicians
      reported having experienced pressure from athletes to prematurely clear them to
      return to participation after a concussion, and 53.7% (n = 483) reported having
      experienced this pressure from coaches. Only 6.6% (n = 59) reported having
      experienced pressure from other clinicians to prematurely clear an athlete to
      return to participation after a concussion. Clinicians reported greater pressure
      from coaches when their departments were under the supervisory purview of the
      athletic department rather than a medical institution. Female clinicians reported
      greater pressure from coaches than male clinicians did. CONCLUSIONS: Most
      clinicians reported experiencing pressure to prematurely return athletes to
      participation after a concussion. Identifying factors that are associated with
      variability in pressure on clinicians during concussion recovery can inform
      potential future strategies to reduce these pressures.

PMID- 26207443
TI  - ?

PMID- 26207445
TI  - ?

PMID- 26207444
TI  - ?

PMID- 26207446
TI  - A Corticosteroid Gene Therapy Combination Strategy to Maximize Intramuscular
      Mediated Delivery in Postischemic Myocardium.

PMID- 26207447
TI  - Cyclopiazonic acid biosynthesis gene cluster gene cpaM is required for speradine
      A biosynthesis.
AB  - Speradine A is a derivative of cyclopiazonic acid (CPA) found in culture of an
      Aspergillus tamarii isolate. Heterologous expression of a predicted
      methyltransferase gene, cpaM, in the cpa biosynthesis gene cluster of A. tamarii
      resulted in the speradine A production in a 2-oxoCPA producing A. oryzae strain,
      indicating cpaM is involved in the speradine A biosynthesis. 

PMID- 26207448
TI  - Changes to the Disordered Phase and Apatite Crystallite Morphology during
      Mineralization by an Acidic Mineral Binding Peptide from Osteonectin.
AB  - Noncollagenous proteins regulate the formation of the mineral constituent in hard
      tissue. The mineral formed contains apatite crystals coated by a functional
      disordered calcium phosphate phase. Although the crystalline phase of bone
      mineral was extensively investigated, little is known about the disordered
      layer's composition and structure, and less is known regarding the function of
      noncollagenous proteins in the context of this layer. In the current study,
      apatite was prepared with an acidic peptide (ON29) derived from the bone/dentin
      protein osteonectin. The mineral formed comprises needle-shaped hydroxyapatite
      crystals like in dentin and a stable disordered phase coating the apatitic
      crystals as shown using X-ray diffraction, transmission electron microscopy, and
      solid-state NMR techniques. The peptide, embedded between the mineral particles,
      reduces the overall phosphate content in the mineral formed as inferred from
      inductively coupled plasma and elemental analysis results. Magnetization
      transfers between disordered phase species and apatitic phase species are
      observed for the first time using 2D (1)H-(31)P heteronuclear correlation NMR
      measurements. The dynamics of phosphate magnetization transfers reveal that ON29
      decreases significantly the amount of water molecules in the disordered phase and
      increases slightly their content at the ordered-disordered interface. The peptide
      decreases hydroxyl to disordered phosphate transfers within the surface layer but
      does not influence transfer within the bulk crystalline mineral. Overall, these
      results indicate that control of crystallite morphology and properties of the
      inorganic component in hard tissue by biomolecules is more involved than just
      direct interaction between protein functional groups and mineral crystal faces.
      Subtler mechanisms such as modulation of the disordered phase composition and
      structural changes at the ordered-disordered interface may be involved. 

PMID- 26207449
TI  - Voltage-Induced Misfolding of Zinc-Replete ALS Mutant Superoxide Dismutase-1.
AB  - The monomerization of Cu, Zn superoxide dismutase (SOD1) is an early step along
      pathways of misfolding linked to amyotrophic lateral sclerosis (ALS).
      Monomerization requires the reversal of two post-translational modifications that
      are thermodynamically favorable: (i) dissociation of active-site metal ions and
      (ii) reduction of intramolecular disulfide bonds. This study found, using amide
      hydrogen/deuterium (H/D) exchange, capillary electrophoresis, and lysine-acetyl
      protein charge ladders, that ALS-linked A4V SOD1 rapidly monomerizes and
      partially unfolds in an external electric field (of physiological strength),
      without loss of metal ions, exposure to disulfide-reducing agents, or Joule
      heating. Voltage-induced monomerization was not observed for metal-free A4V SOD1,
      metal-free WT SOD1, or metal-loaded WT SOD1. Computational modeling suggested a
      mechanism for this counterintuitive effect: subunit macrodipoles of dimeric SOD1
      are antiparallel and amplified 2-fold by metal coordination, which increases
      torque at the dimer interface as subunits rotate to align with the electric
      field. 

PMID- 26207450
TI  - Shear Viscosity of a Unitary Fermi Gas Near the Superfluid Phase Transition.
AB  - We measure the shear viscosity for a resonantly interacting Fermi gas as a
      function of temperature from nearly the ground state through the superfluid phase
      transition into the high temperature regime. Further, we demonstrate an iterative
      method to estimate the local shear viscosity coefficient alpha(S)(theta) versus
      reduced temperature theta from the cloud-averaged measurements ?alpha(S)?, and
      compare alpha(S) to several microscopic theories. We find that alpha(S) reveals
      features that were previously hidden in ?alpha(S)?.

PMID- 26207451
TI  - Third Law of Thermodynamics and The Shape of the Phase Diagram for Systems With a
      First-Order Quantum Phase Transition.
AB  - The third law of thermodynamics constrains the phase diagram of systems with a
      first-order quantum phase transition. For a zero conjugate field, the coexistence
      curve has an infinite slope at T=0. If a tricritical point exists at T>0, then
      the associated tricritical wings are perpendicular to the T=0 plane, but not to
      the zero-field plane. These results are based on the third law and basic
      thermodynamics only, and are completely general. As an explicit example we
      consider the ferromagnetic quantum phase transition in clean metals, where a
      first-order quantum phase transition is commonly observed. 

PMID- 26207452
TI  - Measuring Quantum Coherence with Entanglement.
AB  - Quantum coherence is an essential ingredient in quantum information processing
      and plays a central role in emergent fields such as nanoscale thermodynamics and
      quantum biology. However, our understanding and quantitative characterization of
      coherence as an operational resource are still very limited. Here we show that
      any degree of coherence with respect to some reference basis can be converted to
      entanglement via incoherent operations. This finding allows us to define a novel
      general class of measures of coherence for a quantum system of arbitrary
      dimension, in terms of the maximum bipartite entanglement that can be generated
      via incoherent operations applied to the system and an incoherent ancilla. The
      resulting measures are proven to be valid coherence monotones satisfying all the
      requirements dictated by the resource theory of quantum coherence. We demonstrate
      the usefulness of our approach by proving that the fidelity-based geometric
      measure of coherence is a full convex coherence monotone, and deriving a closed
      formula for it on arbitrary single-qubit states. Our work provides a clear
      quantitative and operational connection between coherence and entanglement, two
      landmark manifestations of quantum theory and both key enablers for quantum
      technologies. 

PMID- 26207453
TI  - Dynamic Nuclear Polarization as Kinetically Constrained Diffusion.
AB  - Dynamic nuclear polarization (DNP) is a promising strategy for generating a
      significantly increased nonthermal spin polarization in nuclear magnetic
      resonance (NMR) and its applications that range from medicine diagnostics to
      material science. Being a genuine nonequilibrium effect, DNP circumvents the need
      for strong magnetic fields. However, despite intense research, a detailed
      theoretical understanding of the precise mechanism behind DNP is currently
      lacking. We address this issue by focusing on a simple instance of DNP-so-called
      solid effect DNP-which is formulated in terms of a quantum central spin model
      where a single electron is coupled to an ensemble of interacting nuclei. We show
      analytically that the nonequilibrium buildup of polarization heavily relies on a
      mechanism which can be interpreted as kinetically constrained diffusion. Beyond
      revealing this insight, our approach furthermore permits numerical studies of
      ensembles containing thousands of spins that are typically intractable when
      formulated in terms of a quantum master equation. We believe that this represents
      an important step forward in the quest of harnessing nonequilibrium many-body
      quantum physics for technological applications. 

PMID- 26207454
TI  - Bounding the Set of Finite Dimensional Quantum Correlations.
AB  - We describe a simple method to derive high performance semidefinite programing
      relaxations for optimizations over complex and real operator algebras in finite
      dimensional Hilbert spaces. The method is very flexible, easy to program, and
      allows the user to assess the behavior of finite dimensional quantum systems in a
      number of interesting setups. We use this method to bound the strength of quantum
      nonlocality in Bell scenarios where the dimension of the parties is bounded from
      above. We derive new results in quantum communication complexity and prove the
      soundness of the prepare-and-measure dimension witnesses introduced in Gallego et
      al., Phys. Rev. Lett. 105, 230501 (2010). Finally, we propose a new dimension
      witness that can distinguish between classical, real, and complex two-level
      systems. 

PMID- 26207455
TI  - From Three-Photon Greenberger-Horne-Zeilinger States to Ballistic Universal
      Quantum Computation.
AB  - Single photons, manipulated using integrated linear optics, constitute a
      promising platform for universal quantum computation. A series of increasingly
      efficient proposals have shown linear-optical quantum computing to be formally
      scalable. However, existing schemes typically require extensive adaptive
      switching, which is experimentally challenging and noisy, thousands of photon
      sources per renormalized qubit, and/or large quantum memories for repeat-until
      success strategies. Our work overcomes all these problems. We present a scheme to
      construct a cluster state universal for quantum computation, which uses no
      adaptive switching, no large memories, and which is at least an order of
      magnitude more resource efficient than previous passive schemes. Unlike previous
      proposals, it is constructed entirely from loss-detecting gates and offers a
      robustness to photon loss. Even without the use of an active loss-tolerant
      encoding, our scheme naturally tolerates a total loss rate ~1.6% in the photons
      detected in the gates. This scheme uses only 3 Greenberger-Horne-Zeilinger states
      as a resource, together with a passive linear-optical network. We fully describe
      and model the iterative process of cluster generation, including photon loss and
      gate failure. This demonstrates that building a linear-optical quantum computer
      needs to be less challenging than previously thought. 

PMID- 26207456
TI  - Force-Induced Dispersion in Heterogeneous Media.
AB  - The effect of a constant applied external force, induced for instance by an
      electric or gravitational field, on the dispersion of Brownian particles in
      periodic media with spatially varying diffusivity, and thus mobility, is studied.
      We show that external forces can greatly enhance dispersion in the direction of
      the applied force and also modify, to a lesser extent and in some cases
      nonmonotonically, dispersion perpendicular to the applied force. Our results thus
      open up the intriguing possibility of modulating the dispersive properties of
      heterogeneous media by using externally applied force fields. These results are
      obtained via a Kubo formula that can be applied to any periodic advection
      diffusion system in any spatial dimension. 

PMID- 26207457
TI  - Model for Thermal Relic Dark Matter of Strongly Interacting Massive Particles.
AB  - A recent proposal is that dark matter could be a thermal relic of 3->2
      scatterings in a strongly coupled hidden sector. We present explicit classes of
      strongly coupled gauge theories that admit this behavior. These are QCD-like
      theories of dynamical chiral symmetry breaking, where the pions play the role of
      dark matter. The number-changing 3->2 process, which sets the dark matter relic
      abundance, arises from the Wess-Zumino-Witten term. The theories give an explicit
      relationship between the 3->2 annihilation rate and the 2->2 self-scattering
      rate, which alters predictions for structure formation. This is a simple
      calculable realization of the strongly interacting massive-particle mechanism. 

PMID- 26207458
TI  - Collisions in Chiral Kinetic Theory.
AB  - Using a covariant formalism, we construct a chiral kinetic theory Lorentz
      invariant to order O(h), which includes collisions. We find a new contribution to
      the particle number current due to the side jumps required by the conservation of
      angular momentum during collisions. We also find a conserved symmetric stress
      energy tensor as well as the H function obeying Boltzmann's H theorem. We
      demonstrate their use by finding a general equilibrium solution and the values of
      the anomalous transport coefficients characterizing the chiral vortical effect. 

PMID- 26207459
TI  - Universality of Corner Entanglement in Conformal Field Theories.
AB  - We study the contribution to the entanglement entropy of (2+1)-dimensional
      conformal field theories (CFTs) coming from a sharp corner in the entangling
      surface. This contribution is encoded in a function a(theta) of the corner
      opening angle, and was recently proposed as a measure of the degrees of freedom
      in the underlying CFT. We show that the ratio a(theta)/C(T), where C(T) is the
      central charge in the stress tensor correlator, is an almost universal quantity
      for a broad class of theories including various higher-curvature holographic
      models, free scalars, and fermions, and Wilson-Fisher fixed points of the O(N)
      models with N=1,2,3. Strikingly, the agreement between these different theories
      becomes exact in the limit theta->pi, where the entangling surface approaches a
      smooth curve. We thus conjecture that the corresponding ratio is universal for
      general CFTs in three dimensions.

PMID- 26207460
TI  - New Fermionic Soft Theorems for Supergravity Amplitudes.
AB  - Soft limits of a massless S matrix are known to reflect the symmetries of the
      theory. In particular, for theories with Goldstone bosons, the double-soft limit
      of scalars reveals the coset structure of the vacuum manifold. In this Letter, we
      propose that such universal double-soft behavior is not only true for scalars,
      but also for spin-1/2 particles in four dimensions and fermions in three
      dimensions. We first consider the Akulov-Volkov theory and demonstrate that the
      double-soft limit of Goldstinos yields the supersymmetry algebra. More
      surprisingly, we also find that amplitudes in 4<=N<=8 supergravity theories in
      four dimensions as well as N=16 supergravity in three dimensions behave
      universally in the double-soft-fermion limit, analogous to the scalar ones. The
      validity of the new soft theorems at loop level is also studied. The results for
      supergravity are beyond what is implied by supersymmetry Ward identities and may
      impose nontrivial constraints on the possible counterterms for supergravity
      theories. 

PMID- 26207461
TI  - Cancellations Between Two-Loop Contributions to the Electron Electric Dipole
      Moment with a CP-Violating Higgs Sector.
AB  - We present a class of cancellation conditions for suppressing the total
      contributions of Barr-Zee diagrams to the electron electric dipole moment (eEDM).
      Such a cancellation is of particular significance after the new eEDM upper limit
      was released by the ACME Collaboration, which strongly constrains the allowed
      magnitude of CP violation in Higgs couplings and hence the feasibility of
      electroweak baryogenesis (EWBG). Explicitly, if both the CP-odd Higgs-photon
      photon (Z boson) and the CP-odd Higgs-electron-positron couplings are turned on,
      a cancellation may occur either between the contributions of a CP-mixing Higgs
      boson, with the other Higgs bosons being decoupled, or between the contributions
      of CP-even and CP-odd Higgs bosons. With a cancellation, large CP violation in
      the Higgs sector is still allowed, yielding successful EWBG. The reopened
      parameter regions would be probed by future neutron, mercury EDM measurements,
      and direct measurements of Higgs CP properties at the Large Hadron Collider Run
      II and future colliders. 

PMID- 26207462
TI  - Could the X(3915) and the X(3930) Be the Same Tensor State?
AB  - By using a combined amplitude analysis of the gammagamma->DD and gammagamma
      >J/psiomega data, we demonstrate that the X(3915), which is quoted as a
      J(PC)=0(++) state in the Particle Data Group table, is favored by the data to be
      a J(PC)=2(++) state appearing in both channels, which means that the X(3915) and
      the X(3930) can be regarded as the same J(PC)=2(++) state. Meanwhile, the data
      also prefer a large helicity-0 contribution of this tensor resonance to the
      amplitudes instead of the helicity-2 dominance assumed by BABAR, which may
      indicate a sizable portion of non-qq components in this state. Identifying the
      X(3915) with the X(3930) and abandoning the helicity-2 dominance for this tensor
      state are helpful for the further understandings of the properties of this state
      and also of the mysterious "XYZ" charmoniumlike resonances.

PMID- 26207463
TI  - Complete Nonrelativistic-QCD Prediction for Prompt Double J/psi Hadroproduction.
AB  - We perform a complete study of prompt double J/psi hadroproduction at leading
      order in the nonrelativistic-QCD factorization framework by including all
      possible pairings of the cc Fock states (1)S(0)([8]), (3)S(1)([1,8]), and
      (3)P(J)([1,8]) with J=0,1,2. We find that the (1)S(0)([8]) and (3)P(J)([8])
      channels of J/psi and psi'} production and the (3)P(J)([1]) and (3)S(1)([8])
      channels of chi(cJ) production, which have been overlooked so far, greatly
      dominate at large invariant masses and rapidity separations of the J/psi pair,
      and that their inclusion nearly fills the large gap between previous incomplete
      predictions within the color-singlet model and the recent measurement by the CMS
      Collaboration at the CERN LHC, leaving room for next-to-leading-order corrections
      of typical size.

PMID- 26207464
TI  - Rod-shaped Nuclei at Extreme Spin and Isospin.
AB  - The anomalous rod shape in carbon isotopes has been investigated in the framework
      of the cranking covariant density functional theory, and two mechanisms to
      stabilize such a novel shape with respect to the bending motion, extreme spin,
      and isospin are simultaneously discussed for the first time in a self-consistent
      and microscopic way. By adding valence neutrons and rotating the system, we have
      found the mechanism stabilizing the rod shape; i.e., the sigma orbitals (parallel
      to the symmetry axis) of the valence neutrons, important for the rod shape, are
      lowered by the rotation due to the Coriolis term. The spin and isospin effects
      enhance the stability of the rod-shaped configuration. This provides a strong
      hint that a rod shape could be realized in nuclei towards extreme spin and
      isospin. 

PMID- 26207465
TI  - Hybridization of Rydberg Electron Orbitals by Molecule Formation.
AB  - The formation of ultralong-range Rydberg molecules is a result of the attractive
      interaction between a Rydberg electron and a polarizable ground-state atom in an
      ultracold gas. In the nondegenerate case, the backaction of the polarizable atom
      on the electronic orbital is minimal. Here we demonstrate how controlled
      degeneracy of the respective electronic orbitals maximizes this backaction and
      leads to stronger binding energies and lower symmetry of the bound dimers.
      Consequently, the Rydberg orbitals hybridize due to the molecular bond. 

PMID- 26207466
TI  - Tuning Bimolecular Chemical Reactions by Electric Fields.
AB  - We develop a theoretical method for solving the quantum mechanical reactive
      scattering problem in the presence of external fields based on a hyperspherical
      coordinate description of the reaction complex combined with the total angular
      momentum representation for collisions in external fields. The method allows us
      to obtain converged results for the chemical reaction LiF+H->Li+HF in an electric
      field. Our calculations demonstrate that, by inducing couplings between states of
      different total angular momenta, electric fields with magnitudes <150  kV/cm give
      rise to resonant scattering and a significant modification of the total reaction
      probabilities, product state distributions, and the branching ratios for reactive
      versus inelastic scattering. 

PMID- 26207467
TI  - Uncovering Quantum Correlations with Time-Multiplexed Click Detection.
AB  - We report on the implementation of a time-multiplexed click detection scheme to
      probe quantum correlations between different spatial optical modes. We
      demonstrate that such measurement setups can uncover nonclassical correlations in
      multimode light fields even if the single mode reductions are purely classical.
      The nonclassical character of correlated photon pairs, generated by a parametric
      down-conversion, is immediately measurable employing the theory of click counting
      instead of low-intensity approximations with photoelectric detection models. The
      analysis is based on second- and higher-order moments, which are directly
      retrieved from the measured click statistics, for relatively high mean photon
      numbers. No data postprocessing is required to demonstrate the effects of
      interest with high significance, despite low efficiencies and experimental
      imperfections. Our approach shows that such novel detection schemes are a
      reliable and robust way to characterize quantum-correlated light fields for
      practical applications in quantum communications. 

PMID- 26207468
TI  - Optical Synthesis of Large-Amplitude Squeezed Coherent-State Superpositions with
      Minimal Resources.
AB  - We propose and experimentally realize a novel versatile protocol that allows the
      quantum state engineering of heralded optical coherent-state superpositions. This
      scheme relies on a two-mode squeezed state, linear mixing, and a n-photon
      detection. It is optimally using expensive non-Gaussian resources to build up
      only the key non-Gaussian part of the targeted state. In the experimental case of
      a two-photon detection based on high-efficiency superconducting nanowire single
      photon detectors, the freely propagating state exhibits a 67% fidelity with a
      squeezed even coherent-state superposition with a size |alpha|(2)=3. The
      demonstrated procedure and the achieved rate will facilitate the use of such
      superpositions in subsequent protocols, including fundamental tests and optical
      hybrid quantum information implementations.

PMID- 26207469
TI  - Hybrid Matter-Wave-Microwave Solitons Produced by the Local-Field Effect.
AB  - It was recently found that the electric local-field effect (LFE) can lead to a
      strong coupling of atomic Bose-Einstein condensates (BECs) to off-resonant
      optical fields. We demonstrate that the magnetic LFE gives rise to a previously
      unexplored mechanism for coupling a (pseudo-) spinor BEC or fermion gas to
      microwaves (MWs). We present a theory for the magnetic LFE and find that it gives
      rise to a short-range attractive interaction between two components of the
      (pseudo) spinor, and a long-range interaction between them. The latter
      interaction, resulting from deformation of the magnetic field, is locally
      repulsive but globally attractive, in sharp contrast with its counterpart for the
      optical LFE, produced by phase modulation of the electric field. Our analytical
      results, confirmed by the numerical computations, show that the long-range
      interaction gives rise to modulational instability of the spatially uniform
      state, and it creates stable ground states in the form of hybrid matter-wave
      microwave solitons (which seem like one-dimensional magnetic monopoles), with a
      size much smaller than the MW wavelength, even in the presence of arbitrarily
      strong contact intercomponent repulsion. The setting is somewhat similar to
      exciton-polaritonic condensates in semiconductor microcavities. The release of
      matter waves from the soliton may be used for the realization of an atom laser.
      The analysis also applies to molecular BECs with rotational states coupled by the
      electric MW field. 

PMID- 26207470
TI  - Femtosecond Enhancement Cavities in the Nonlinear Regime.
AB  - We combine high-finesse optical resonators and spatial-spectral interferometry to
      a highly phase-sensitive investigation technique for nonlinear light-matter
      interactions. We experimentally validate an ab initio model for the nonlinear
      response of a resonator housing a gas target, permitting the global optimization
      of intracavity conversion processes like high-order harmonic generation. We
      predict the feasibility of driving intracavity high-order harmonic generation far
      beyond intensity limitations observed in state-of-the-art systems by exploiting
      the intracavity nonlinearity to compress the pulses in time. 

PMID- 26207471
TI  - Extraordinarily Large Optical Cross Section for Localized Single Nanoresonator.
AB  - Using an optical nanoresonator to realize extreme concentration of light at
      subwavelength nanoscale dimensions is of both fundamental and practical
      significance. Unfortunately, the optical cross section of an isotropic
      nanoresonator is determined by the resonant wavelength, which unfavorably limits
      the highest concentration ratio. Here we show that the cross section of a
      localized subwavelength resonator can be drastically enhanced by orders of
      magnitude. A single microscopic nanoresonator could exhibit a macroscopic optical
      cross section. We further show that the enhancement can be implemented in simple
      dielectric structures that are readily compatible with optoelectronic
      integration. The giant optical cross section of a nano-object provides a
      versatile platform to create extremely strong light-matter interactions at the
      nanoscale. 

PMID- 26207472
TI  - Inertial-Range Reconnection in Magnetohydrodynamic Turbulence and in the Solar
      Wind.
AB  - In situ spacecraft data on the solar wind show events identified as magnetic
      reconnection with wide outflows and extended "X lines," 10(3)-10(4) times ion
      scales. To understand the role of turbulence at these scales, we make a case
      study of an inertial-range reconnection event in a magnetohydrodynamic
      simulation. We observe stochastic wandering of field lines in space, breakdown of
      standard magnetic flux freezing due to Richardson dispersion, and a broadened
      reconnection zone containing many current sheets. The coarse-grain magnetic
      geometry is like large-scale reconnection in the solar wind, however, with a
      hyperbolic flux tube or apparent X line extending over integral length scales.

PMID- 26207473
TI  - Relativistic Plasma Polarizer: Impact of Temperature Anisotropy on Relativistic
      Transparency.
AB  - 3D particle-in-cell simulations demonstrate that the enhanced transparency of a
      relativistically hot plasma is sensitive to how the energy is partitioned between
      different degrees of freedom. For an anisotropic electron distribution,
      propagation characteristics, like the critical density, will depend on the
      polarization of the electromagnetic wave. Despite the onset of the Weibel
      instability in such plasmas, the anisotropy can persist long enough to affect
      laser propagation. This plasma can then function as a polarizer or a wave plate
      to dramatically alter the pulse polarization. 

PMID- 26207474
TI  - Multiscale Nature of the Dissipation Range in Gyrokinetic Simulations of Alfvenic
      Turbulence.
AB  - Nonlinear energy transfer and dissipation in Alfven wave turbulence are analyzed
      in the first gyrokinetic simulation spanning all scales from the tail of the MHD
      range to the electron gyroradius scale. For typical solar wind parameters at 1
      AU, about 30% of the nonlinear energy transfer close to the electron gyroradius
      scale is mediated by modes in the tail of the MHD cascade. Collisional
      dissipation occurs across the entire kinetic range k(?)rho(I)?1. Both mechanisms
      thus act on multiple coupled scales, which have to be retained for a
      comprehensive picture of the dissipation range in Alfvenic turbulence.

PMID- 26207475
TI  - Quantum Signature of Analog Hawking Radiation in Momentum Space.
AB  - We consider a sonic analog of a black hole realized in the one-dimensional flow
      of a Bose-Einstein condensate. Our theoretical analysis demonstrates that one-
      and two-body momentum distributions accessible by present-day experimental
      techniques provide clear direct evidence (i) of the occurrence of a sonic
      horizon, (ii) of the associated acoustic Hawking radiation, and (iii) of the
      quantum nature of the Hawking process. The signature of the quantum behavior
      persists even at temperatures larger than the chemical potential. 

PMID- 26207476
TI  - Shortcut to Adiabaticity for an Anisotropic Gas Containing Quantum Defects.
AB  - We present a shortcut to adiabaticity (STA) protocol applicable to 3D unitary
      Fermi gases and 2D weakly interacting Bose gases containing defects such as
      vortices or solitons. Our protocol relies on a new class of exact scaling
      solutions in the presence of anisotropic time-dependent harmonic traps. It
      connects stationary states in initial and final traps having the same frequency
      ratios. The resulting scaling laws exhibit a universal form and also apply to the
      classical Boltzmann gas. The duration of the STA can be made very short so as to
      realize a quantum quench from one stationary state to another. When applied to an
      anisotropically trapped superfluid gas, the STA conserves the shape of the
      quantum defects hosted by the cloud, thereby acting like a perfect microscope,
      which sharply contrasts with their strong distortion occurring during the free
      expansion of the cloud. 

PMID- 26207477
TI  - Metasurface-Enabled Remote Quantum Interference.
AB  - An anisotropic quantum vacuum (AQV) opens novel pathways for controlling light
      matter interaction in quantum optics, condensed matter physics, etc. Here, we
      theoretically demonstrate a strong AQV over macroscopic distances enabled by a
      judiciously designed array of subwavelength-scale nanoantennas-a metasurface. We
      harness the phase-control ability and the polarization-dependent response of the
      metasurface to achieve strong anisotropy in the decay rate of a quantum emitter
      located over distances of hundreds of wavelengths. Such an AQV induces quantum
      interference among radiative decay channels in an atom with orthogonal
      transitions. Quantum vacuum engineering with metasurfaces holds promise for
      exploring new paradigms of long-range light-matter interaction for atom optics,
      solid-state quantum optics, quantum information processing, etc. 

PMID- 26207478
TI  - Applicability of Macroscopic Wear and Friction Laws on the Atomic Length Scale.
AB  - Using molecular dynamics, we simulate the abrasion process of an atomically rough
      Fe surface with multiple hard abrasive particles. By quantifying the nanoscopic
      wear depth in a time-resolved fashion, we show that Barwell's macroscopic wear
      law can be applied at the atomic scale. We find that in this multiasperity
      contact system, the Bowden-Tabor term, which describes the friction force as a
      function of the real nanoscopic contact area, can predict the kinetic friction
      even when wear is involved. From this the Derjaguin-Amontons-Coulomb friction law
      can be recovered, since we observe a linear dependence of the contact area on the
      applied load in accordance with Greenwood-Williamson contact mechanics. 

PMID- 26207479
TI  - Analogies Between the Cracking Noise of Ethanol-Dampened Charcoal and
      Earthquakes.
AB  - We report on an extensive characterization of the cracking noise produced by
      charcoal samples when dampened with ethanol. We argue that the evaporation of
      ethanol causes transient and irregularly distributed internal stresses that
      promote the fragmentation of the samples and mimic some situations found in
      mining processes. The results show that, in general, the most fundamental seismic
      laws ruling earthquakes (the Gutenberg-Richter law, the unified scaling law for
      the recurrence times, Omori's law, the productivity law, and Bath's law) hold
      under the conditions of the experiment. Some discrepancies were also identified
      (a smaller exponent in the Gutenberg-Richter law, a stationary behavior in the
      aftershock rates for long times, and a double power-law relationship in the
      productivity law) and are related to the different loading conditions. Our
      results thus corroborate and elucidate the parallel between the seismic laws and
      fracture experiments caused by a more complex loading condition that also occurs
      in natural and induced seismicity (such as long-term fluid injection and gas-rock
      outbursts in mining processes). 

PMID- 26207480
TI  - Investigation of the Electromagnetic Radiation Emitted by Sub-GeV Electrons in a
      Bent Crystal.
AB  - The radiation emitted by 855 MeV electrons via planar channeling and volume
      reflection in a 30.5-MUm-thick bent Si crystal has been investigated at the MAMI
      (Mainzer Mikrotron) accelerator. The spectral intensity was much more intense
      than for an equivalent amorphous material, and peaked in the MeV range in the
      case of channeling radiation. Differently from a straight crystal, also for an
      incidence angle larger than the Lindhard angle, the spectral intensity remains
      nearly as high as for channeling. This is due to volume reflection, for which the
      intensity remains high at a large incidence angle over the whole angular
      acceptance, which is equal to the bending angle of the crystal. Monte Carlo
      simulations demonstrated that incoherent scattering significantly influences both
      the radiation spectrum and intensity, either for channeling or volume reflection.
      In the latter case, it has been shown that incoherent scattering increases the
      radiation intensity due to the contribution of volume-captured particles. As a
      consequence, the experimental spectrum becomes a mixture of channeling and pure
      volume reflection radiations. These results allow a better understanding of the
      radiation emitted by electrons subjected to coherent interactions in bent
      crystals within a still-unexplored energy range, which is relevant for possible
      applications for innovative and compact x-ray or gamma-ray sources. 

PMID- 26207481
TI  - Glassy Dynamics in Geometrically Frustrated Coulomb Liquids without Disorder.
AB  - We show that introducing long-range Coulomb interactions immediately lifts the
      massive ground state degeneracy induced by geometric frustration for electrons on
      quarter-filled triangular lattices in the classical limit. Important consequences
      include the stabilization of a stripe-ordered crystalline (global) ground state,
      but also the emergence of very many low-lying metastable states with amorphous
      "stripe-glass" spatial structures. Melting of the stripe order thus leads to a
      frustrated Coulomb liquid at intermediate temperatures, showing remarkably slow
      (viscous) dynamics, with very long relaxation times growing in Arrhenius fashion
      upon cooling, as typical of strong glass formers. On shorter time scales, the
      system falls out of equilibrium and displays the aging phenomena characteristic
      of supercooled liquids above the glass transition. Our results show remarkable
      similarity with the recent observations of charge-glass behavior in ultraclean
      triangular organic materials of the theta-(BEDT-TTF)(2) family.

PMID- 26207482
TI  - Helical Defect Packings in a Quasi-One-Dimensional System of Cylindrically
      Confined Hard Spheres.
AB  - We use a combination of analytical theory and molecular dynamics simulation to
      study the inherent structure landscape of a system of hard spheres confined to
      narrow cylindrical channels of diameter 1+?[3]/2<H(d)/sigma<1+4?[3]/7. The most
      dense packing is a perfect, symmetrical single helix. The presence of topological
      defects that change the local chirality of the helix lowers the packing density
      and alters the local packing structure. The helical sections between defects
      become asymmetrical and are better described as a double helix with angular
      twists between the first and second nearest neighbors that are determined by the
      defect separation distance. Increasing the fraction of defects unwinds the two
      helical strands so that the least dense structure is a nonhelical packing of two
      zigzag chains. We also show that the packing effects of the helical section
      induce a long-range, entropically driven attraction between the defects.

PMID- 26207483
TI  - Quantum Critical Elasticity.
AB  - We discuss elastic instabilities of the atomic crystal lattice at zero
      temperature. Because of long-range shear forces of the solid, at such transitions
      the phonon velocities vanish, if at all, only along certain crystallographic
      directions, and, consequently, the critical phonon fluctuations are suppressed to
      a lower dimensional manifold and governed by a Gaussian fixed point. In the case
      of symmetry-breaking elastic transitions, a characteristic critical phonon
      thermodynamics arises that is found, e.g., to violate Debye's T(3) law for the
      specific heat. We point out that quantum critical elasticity is triggered
      whenever a critical soft mode couples linearly to the strain tensor. In
      particular, this is relevant for the electronic Ising-nematic quantum phase
      transition in a tetragonal crystal as discussed in the context of certain
      cuprates, ruthenates, and iron-based superconductors.

PMID- 26207484
TI  - Scanning Quantum Dot Microscopy.
AB  - We introduce a scanning probe technique that enables three-dimensional imaging of
      local electrostatic potential fields with subnanometer resolution. Registering
      single electron charging events of a molecular quantum dot attached to the tip of
      an atomic force microscope operated at 5 K, equipped with a qPlus tuning fork, we
      image the quadrupole field of a single molecule. To demonstrate quantitative
      measurements, we investigate the dipole field of a single metal adatom adsorbed
      on a metal surface. We show that because of its high sensitivity the technique
      can probe electrostatic potentials at large distances from their sources, which
      should allow for the imaging of samples with increased surface roughness. 

PMID- 26207485
TI  - Silicon Reactivity at the Ag(111) Surface.
AB  - The modelization of silicene on Ag(111) is generally based on the assumption of a
      complete immiscibility between silicon and silver. However, there are recent
      reports that growth occurs inside the first layer of the Ag(111) terraces rather
      than on top of them. Here, we report on a combined density functional theory and
      scanning tunneling microscopy study unveiling the basic exchange mechanism
      between Si and the topmost layer Ag atoms and modeling the nucleation process.
      Our findings demonstrate that a strong Si-Ag interaction must be considered to
      properly describe the Si/Ag(111) interface. 

PMID- 26207486
TI  - Parity-Breaking Phases of Spin-Orbit-Coupled Metals with Gyrotropic,
      Ferroelectric, and Multipolar Orders.
AB  - We study Fermi liquid instabilities in spin-orbit-coupled metals with inversion
      symmetry. By introducing a canonical basis for the doubly degenerate Bloch bands
      in momentum space, we derive the general form of Landau interaction functions. A
      variety of time-reversal-invariant, parity-breaking phases is found, whose Fermi
      surface is spontaneously deformed and spin split. In terms of symmetry, these
      phases possess gyrotropic, ferroelectric, and multipolar orders. The
      ferroelectric and multipolar phases are accompanied by structural distortions,
      from which the electronic orders can be identified. The gyrotropic phase exhibits
      a unique nonlinear optical property. We identify correlated electron materials
      that exhibit these parity-breaking phases, including LiOsO(3) and Cd(2)Re(2)O(7).

PMID- 26207487
TI  - Model of Electronic Structure and Superconductivity in Orbitally Ordered FeSe.
AB  - We provide a band structure with low-energy properties consistent with recent
      photoemission and quantum oscillation measurements on FeSe, assuming mean-field
      like site- and/or bond-centered ferro-orbital ordering at the structural
      transition. We show how the resulting model provides a consistent explanation of
      the temperature dependence of the measured Knight shift and the spin-relaxation
      rate. Furthermore, the superconducting gap structure obtained from spin
      fluctuation theory exhibits nodes on the electron pockets, consistent with the V
      shaped density of states obtained by tunneling spectroscopy on this material, and
      the temperature dependence of the London penetration depth. 

PMID- 26207488
TI  - Line of Dirac Nodes in Hyperhoneycomb Lattices.
AB  - We propose a family of structures that have "Dirac loops," closed lines of Dirac
      nodes in momentum space, on which the density of states vanishes linearly with
      energy. Those lattices all possess the planar trigonal connectivity present in
      graphene, but are three dimensional. We show that their highly anisotropic and
      multiply connected Fermi surface leads to quantized Hall conductivities in three
      dimensions for magnetic fields with toroidal geometry. In the presence of spin
      orbit coupling, we show that those structures have topological surface states. We
      discuss the feasibility of realizing the structures as new allotropes of carbon. 

PMID- 26207489
TI  - Anisotropic Particle-Hole Excitations in Black Phosphorus.
AB  - We report on the energy- and momentum-resolved optical response of black
      phosphorus (BP) in its bulk form. Along the armchair direction of the puckered
      layers, we find a highly dispersive mode that is strongly suppressed in the
      perpendicular (zigzag) direction. This mode emerges out of the single-particle
      continuum for finite values of momentum and is therefore interpreted as an
      exciton. We argue that this exciton, which has already been predicted
      theoretically for phosphorene-the monolayer form of BP-can be detected by
      conventional optical spectroscopy in the two-dimensional case and might pave the
      way for optoelectronic applications of this emerging material. 

PMID- 26207490
TI  - Spin Hall Effect in Disordered Organic Solids.
AB  - We study the spin Hall effect (SHE) in disordered pi-conjugated organic solids,
      where individual molecules are oriented randomly and electrical conduction is via
      carrier hopping. The SHE, which arises from interference between direct (i->j)
      and indirect (i->k->j) hoppings in a triad consisting of three molecules i, j,
      and k, is found to be proportional to lambda(n(i)*n(j)+n(j)*n(k)+n(k)*n(i)),
      where lambda is the spin admixture of pi electrons due to the spin-orbit coupling
      and n(i) is the orientation vector of molecule i. Electrical conductivity
      sigma(qq) (q=x,y,z) and spin Hall conductivity sigma(sh) are computed by
      numerically solving the master equations of a system containing 32*32*32
      molecules and summing over contributions from all triads in the system. The
      obtained value of the spin Hall angle Theta(sh) is consistent with experimental
      data in PEDOT: PSS, with a predicted temperature dependence of logTheta(sh)~T(
      1/4).

PMID- 26207491
TI  - Fullerene C(60) Simulated with a Superconducting Microwave Resonator and Test of
      the Atiyah-Singer Index Theorem.
AB  - We report first experiments with a macroscopic-size superconducting microwave
      resonator that has the geometric structure of the C(60) fullerene molecule. Our
      high-resolution measurements reveal the exceptional spectral properties that stem
      from the icosahedral symmetry of its carbon lattice. In particular, they allow us
      to determine the number of zero-energy modes, i.e., of modes with energy values
      at the Dirac point existent in the band structure due to the hexagonal
      arrangements of the carbon atoms, and to test the Atiyah-Singer index theorem
      which relates this number to the topology of the curved carbon lattice.

PMID- 26207492
TI  - Continuous Preparation of a Fractional Chern Insulator.
AB  - We present evidence of a direct, continuous quantum phase transition between a
      Bose superfluid and the nu=1/2 fractional Chern insulator in a microscopic
      lattice model. In the process, we develop a detailed field theoretic description
      of this transition in terms of the low energy vortex dynamics. The theory
      explicitly accounts for the structure of lattice symmetries and predicts a Landau
      forbidden transition that is protected by inversion. That the transition is
      continuous enables the quasiadiabatic preparation of the fractional Chern
      insulator in nonequilibrium, quantum optical systems. 

PMID- 26207493
TI  - Self-Assembled Si(111) Surface States: 2D Dirac Material for THz Plasmonics.
AB  - Graphene, the first discovered 2D Dirac material, has had a profound impact on
      science and technology. In the last decade, we have witnessed huge advances in
      graphene related fundamental and applied research. Here, based on first
      principles calculations, we propose a new 2D Dirac band on the Si(111) surface
      with 1/3 monolayer halogen coverage. The sp(3) dangling bonds form a honeycomb
      superstructure on the Si(111) surface that results in an anisotropic Dirac band
      with a group velocity (~10(6)  m/s) comparable to that in graphene. Most
      remarkably, the Si-based surface Dirac band can be used to excite a tunable THz
      plasmon through electron-hole doping. Our results demonstrate a new way to design
      Dirac states on a traditional semiconductor surface, so as to make them directly
      compatible with Si technology. We envision this new type of Dirac material to be
      generalized to other semiconductor surfaces with broad applications.

PMID- 26207494
TI  - Optically Induced Nuclear Spin Polarization in the Quantum Hall Regime: The
      Effect of Electron Spin Polarization through Exciton and Trion Excitations.
AB  - We study nuclear spin polarization in the quantum Hall regime through the
      optically pumped electron spin polarization in the lowest Landau level. The
      nuclear spin polarization is measured as a nuclear magnetic field B(N) by means
      of the sensitive resistive detection. We find the dependence of B(N) on the
      filling factor nonmonotonic. The comprehensive measurements of B(N) with the help
      of the circularly polarized photoluminescence measurements indicate the
      participation of the photoexcited complexes, i.e., the exciton and trion (charged
      exciton), in nuclear spin polarization. On the basis of a novel estimation method
      of the equilibrium electron spin polarization, we analyze the experimental data
      and conclude that the filling factor dependence of B(N) is understood by the
      effect of electron spin polarization through excitons and trions.

PMID- 26207495
TI  - Topological Crystalline Superconductivity in Locally Noncentrosymmetric
      Multilayer Superconductors.
AB  - Topological crystalline superconductivity in locally noncentrosymmetric
      multilayer superconductors (SCs) is proposed. We study the odd-parity pair
      density wave (PDW) state induced by the spin-singlet pairing interaction through
      the spin-orbit coupling. It is shown that the PDW state is a topological
      crystalline SC protected by a mirror symmetry, although it is topologically
      trivial according to the classification based on the standard topological
      periodic table. The topological property of the mirror subsectors is intuitively
      explained by adiabatically changing the Bogoliubov-de Gennes Hamiltonian. A
      subsector of the bilayer PDW state reduces to the two-dimensional
      noncentrosymmetric SC, while a subsector of the trilayer PDW state is
      topologically equivalent to the spinless p-wave SC. Chiral Majorana edge modes in
      trilayers can be realized without Cooper pairs in the spin-triplet channel and
      chemical potential tuning. 

PMID- 26207496
TI  - Stability of the Zhang-Rice Singlet with Doping in Lanthanum Strontium Copper
      Oxide Across the Superconducting Dome and Above.
AB  - The spin character of the states at the top of the valence band in doped La(2
      x)Sr(x)CuO(4) (x=0.03, 0.07, 0.15, 0.22, and 0.30) has been investigated using
      spin-polarized resonant photoemission. A clear Zhang-Rice singlet (ZRS) is
      observed at all doping levels. Its stability and polarization are preserved as a
      function of doping, suggesting that the concept of the ZRS can be used across a
      wide doping range and up to the metallic nonsuperconducting overdoped regime. The
      results are significant for theoretical models that use the ZRS approximation and
      for the understanding of the peculiar interplay between the ZRS and the remaining
      localized spins.

PMID- 26207497
TI  - Infrared Study of the Spin Reorientation Transition and Its Reversal in the
      Superconducting State in Underdoped Ba(1-x)K(x)Fe(2)As(2).
AB  - With infrared spectroscopy we investigated the spin-reorientation transition from
      an orthorhombic antiferromagnetic (o-AF) to a tetragonal AF (t-AF) phase and the
      reentrance of the o-AF phase in the superconducting state of underdoped Ba(1
      x)K(x)Fe(2)As(2). In agreement with the predicted transition from a single-Q to a
      double-Q AF structure, we found that a distinct spin density wave develops in the
      t-AF phase. The pair breaking peak of this spin density wave acquires much more
      low-energy spectral weight than the one in the o-AF state which indicates that it
      competes more strongly with superconductivity. We also observed additional phonon
      modes in the t-AF phase which likely arise from a Brillouin-zone folding that is
      induced by the double-Q magnetic structure with two Fe sublattices exhibiting
      different magnitudes of the magnetic moment.

PMID- 26207498
TI  - Antibunched Photons from Inelastic Cooper-Pair Tunneling.
AB  - We demonstrate theoretically that charge transport across a Josephson junction,
      voltage-biased through a resistive environment, produces antibunched photons. We
      develop a continuous-mode description of the emitted radiation field in a semi
      infinite transmission line terminated by the Josephson junction. Within a
      perturbative treatment in powers of the tunneling coupling across the Josephson
      junction, we capture effects originating in charging dynamics of consecutively
      tunneling Cooper pairs. We find that within a feasible experimental setup the
      Coulomb blockade provided by high zero-frequency impedance can be used to create
      antibunched photons at a very high rate and in a very versatile frequency window
      ranging from a few GHz to a THz. 

PMID- 26207499
TI  - Antagonistic In-Plane Resistivity Anisotropies from Competing Fluctuations in
      Underdoped Cuprates.
AB  - One of the prime manifestations of an anisotropic electronic state in underdoped
      cuprates is the in-plane resistivity anisotropy Deltarho=(rho(a)-rho(b))/rho(b).
      Here we use a Boltzmann-equation approach to compute the contribution to Deltarho
      arising from scattering by anisotropic charge and spin fluctuations, which have
      been recently observed experimentally. While the anisotropy in the charge
      fluctuations is manifested in the correlation length, the anisotropy in the spin
      fluctuations emerges only in the structure factor. As a result, we find that spin
      fluctuations favor Deltarho>0, whereas charge fluctuations promote Deltarho<0,
      which are both consistent with the doping dependence of Deltarho observed in
      YBa(2)Cu(3)O(7). We also discuss the role played by CuO chains in these
      materials, and propose transport experiments in strained HgBa(2)CuO(4) and
      Nd(2)CuO(4) to probe directly the different resistivity anisotropy regimes.

PMID- 26207500
TI  - Dichotomy between the Hole and Electron Behavior in Multiband Superconductor FeSe
      Probed by Ultrahigh Magnetic Fields.
AB  - Magnetoresistivity rho(xx) and Hall resistivity rho(xy) in ultrahigh magnetic
      fields up to 88 T are measured down to 0.15 K to clarify the multiband electronic
      structure in high-quality single crystals of superconducting FeSe. At low
      temperatures and high fields we observe quantum oscillations in both resistivity
      and the Hall effect, confirming the multiband Fermi surface with small volumes.
      We propose a novel approach to identify from magnetotransport measurements the
      sign of the charge carriers corresponding to a particular cyclotron orbit in a
      compensated metal. The observed significant differences in the relative
      amplitudes of the quantum oscillations between the rho(xx) and rho(xy)
      components, together with the positive sign of the high-field rho(xy), reveal
      that the largest pocket should correspond to the hole band. The low-field
      magnetotransport data in the normal state suggest that, in addition to one hole
      and one almost compensated electron band, the orthorhombic phase of FeSe exhibits
      an additional tiny electron pocket with a high mobility.

PMID- 26207501
TI  - Photon-Statistics Excitation Spectroscopy of a Quantum-Dot Micropillar Laser.
AB  - We introduce photon-statistics excitation spectroscopy and exemplarily apply it
      to a quantum-dot micropillar laser. Both the intensity and the photon number
      statistics of the emission from the micropillar show a strong dependence on the
      photon statistics of the light used for excitation of the sample. The results
      under coherent and pseudothermal excitation reveal that a description of the
      laser properties in terms of mean input photon numbers is not sufficient. It is
      demonstrated that the micropillar acts as a superthermal light source when
      operated close to its threshold. Possible applications for important
      spectroscopic techniques are discussed. 

PMID- 26207502
TI  - Observation of High Angular Momentum Excitons in Cuprous Oxide.
AB  - The recent observation of dipole-allowed P excitons up to principal quantum
      numbers of n=25 in cuprous oxide has given insight into exciton states with
      unprecedented spectral resolution. While so far the exciton description as a
      hydrogenlike complex has been fully adequate for cubic crystals, we demonstrate
      here distinct deviations: The breaking of rotational symmetry leads to mixing of
      high angular momentum F and H excitons with the P excitons so that they can be
      observed in absorption. The F excitons show a threefold splitting that depends
      systematically on n, in agreement with theoretical considerations. From detailed
      comparison of experiment and theory we determine the cubic anisotropy parameter
      of the Cu(2)O valence band.

PMID- 26207503
TI  - High Gain Submicrometer Optical Amplifier at Near-Infrared Communication Band.
AB  - Nanoscale near-infrared optical amplification is important but remains a
      challenge to achieve. Here we report a unique design of silicon and erbium
      silicate core-shell nanowires for high gain submicrometer optical amplification
      in the near-infrared communication band. The high refraction index silicon core
      is used to tightly confine the optical field within the submicron structures, and
      the single crystalline erbium-ytterbium silicates shell is used as the highly
      efficient gain medium. Both theoretical and experimental results show that, by
      systematically tuning the core diameter and shell thickness, a large portion of
      the optical power can be selectively confined to the erbium silicate shell gain
      medium to enable a low loss waveguide and high gain optical amplifier.
      Experimental results further demonstrate that an optimized core-shell nanowire
      can exhibit an excellent net gain up to 31  dB mm(-1), which is more than 20
      times larger than the previously reported best results on the micron-scale
      optical amplifiers.

PMID- 26207504
TI  - Direct Evidence of Flexomagnetoelectric Effect Revealed by Single-Molecule
      Spectroscopy.
AB  - We report direct evidence of the electric field induced by a magnetization
      inhomogeneity in an iron garnet film. This inhomogeneity was created by the
      nonuniform magnetic fields generated at domain boundaries of a type-I
      superconductor in the intermediate state. At liquid helium temperatures, Stark
      shifts of sharp single-molecule zero-phonon lines were used to probe the local
      electric fields generated by this flexomagnetoelectric effect. The measured
      electric fields are in accordance with theoretical estimations. 

PMID- 26207505
TI  - Spin Blocking in the Correlated Double-Electron Capture from Metal Surfaces.
AB  - The resonant capture of electrons from a metallic surface into the outer shell of
      a helium ion creates doubly excited states in a spin singlet (??) or triplet (??)
      configuration. Here it is shown that the capture of one or two electrons can be
      described in a simple quantitative model, and the capture of two electrons by
      He(++) proceeds in a single step. The double capture of electrons from the Fermi
      energy of the metal is dominated by the spin dependent electron correlation that
      blocks the occupation of triplet states in the ion, but creates a singlet two
      hole final state at the surface, related to the concept of the exchange
      correlation hole.

PMID- 26207506
TI  - Craters and Granular Jets Generated by Underground Cavity Collapse.
AB  - We study experimentally the cratering process due to the explosion and collapse
      of a pressurized air cavity inside a sand bed. The process starts when the cavity
      breaks and the liberated air then rises through the overlying granular layer and
      produces a violent eruption; it depressurizes the cavity and, as the gas is
      released, the sand sinks under gravity, generating a crater. We find that the
      crater dimensions are totally determined by the cavity volume; the pressure does
      not affect the morphology because the air is expelled vertically during the
      eruption. In contrast with impact craters, the rim is flat and, regardless of the
      cavity shape, it evolves into a circle as the cavity depth increases or if the
      chamber is located deep enough inside the bed, which could explain why most of
      the subsidence craters observed in nature are circular. Moreover, for shallow
      spherical cavities, a collimated jet emerges from the collision of sand
      avalanches that converge concentrically at the bottom of the depression,
      revealing that collapse under gravity is the main mechanism driving the jet
      formation. 

PMID- 26207507
TI  - Turning Bacteria Suspensions into Superfluids.
AB  - The rheological response under simple shear of an active suspension of
      Escherichia coli is determined in a large range of shear rates and
      concentrations. The effective viscosity and the time scales characterizing the
      bacterial organization under shear are obtained. In the dilute regime, we bring
      evidence for a low-shear Newtonian plateau characterized by a shear viscosity
      decreasing with concentration. In the semidilute regime, for particularly active
      bacteria, the suspension displays a "superfluidlike" transition where the viscous
      resistance to shear vanishes, thus showing that, macroscopically, the activity of
      pusher swimmers organized by shear is able to fully overcome the dissipative
      effects due to viscous loss. 

PMID- 26207508
TI  - Comment on "Determination of the Nitrogen Vacancy as a Shallow Compensating
      Center in GaN Doped with Divalent Metals".

PMID- 26207509
TI  - Buckeridge et al. Reply.

PMID- 26207510
TI  - Perspectives of hospitalized patients with mental disorders and their clinicians
      on vocational goals, barriers, and steps to overcome barriers.
AB  - BACKGROUND: People with mental disorders experience difficulties with finding
      competitive jobs. In countries with longer psychiatric hospitalization periods,
      the vocational rehabilitation process can start during hospitalization. Yet,
      rehabilitation can be hindered by a lack of focus by clinicians on the patients'
      vocational goals and a lack of agreement between clinicians and patients. AIMS:
      To compare (i) vocational goals, (ii) barriers to employment and (iii) support
      needed to overcome barriers faced by patients. METHOD: The paired data-set
      comprised 733 hospitalized patients and their 279 clinicians. Patients selected
      their vocational goals and clinicians indicated options that seemed realistic.
      Patients and clinicians indicated how many barriers exist and what support is
      needed to overcome barriers. RESULTS: Almost 45% of patients prefer competitive
      jobs, while 32% of clinicians find this realistic, indicating a moderate
      relationship between patients' goals and clinicians' perceptions. Patients and
      clinicians also differ in their perception of the level of barriers and types of
      support to overcome them. Patients perceive fewer vocational barriers than
      clinicians and prefer less intense vocational support options. CONCLUSIONS:
      Patients and clinicians have different perspectives concerning vocational
      recovery. Improving vocational rehabilitation requires a stronger alignment
      between patients and clinicians' vocational goals and barriers.

PMID- 26207511
TI  - Synthesis and in vitro evaluation of 4-substituted furano[3,2-c]
      tetrahydroquinolines as potential anti-cancer agents.
AB  - A convenient and mild method for the synthesis of substituted furano [3,2
      c]tetrahydroquinoline derivatives was developed, using the multi-component
      Povarov reaction. Of the synthesized tetrahydroquinoline derivatives, compound
      10a displayed the greatest cellular proliferation inhibitory activities with IC50
      values of 2.5-16.7 MUmol/l. In addition, 10a induced murine C6 glioma cell
      apoptosis in a dose-dependent manner by up-regulating the expression of Bax,
      caspase-3, and caspase-9, and by down-regulating Bcl-2. Our findings suggest that
      these novel compounds have potential as therapeutic agents via inducing
      mitochondrial apoptosis. 

PMID- 26207512
TI  - Anthraquinone profile, antioxidant and enzyme inhibitory effect of root extracts
      of eight Asphodeline taxa from Turkey: can Asphodeline roots be considered as a
      new source of natural compounds?
AB  - Plant-based foods have become attractive for scientists and food producers.
      Beneficial effects related to their consumption as dietary supplements are due to
      the presence of natural occurring secondary metabolites. In this context, studies
      on these products are important for natural and safely food ingredients
      evaluation. The aim of this study was to evaluate root extract of eight
      Asphodeline species as antioxidants, enzyme inhibitors and phytochemical content.
      Spectrophotometric antioxidant and enzyme inhibitory assays were performed. Total
      phenolic and flavonoids contents as well as the chemical free-anthraquinones
      profiles were determined using routinely procedure (HPLC-PDA). Data show that
      Asphodeline roots can be considered as a new source of natural compounds and can
      be used as a valuable dietary supplement. Some differences related to biological
      activities can be inferred to other phytochemicals that can be considered in the
      future for their synergic or competitive activities. 

PMID- 26207513
TI  - Coumarin or benzoxazinone based novel carbonic anhydrase inhibitors: synthesis,
      molecular docking and anticonvulsant studies.
AB  - Among many others, coumarin derivatives are known to show human carbonic
      anhydrase (hCA) inhibitory activity. Since hCA inhibition is one of the
      underlying mechanisms that account for the activities of some antiepileptic drugs
      (AEDs), hCA inhibitors are expected to have anti-seizure properties. There are
      also several studies reporting compounds with an imidazole and/or benzimidazole
      moiety which exert these pharmacological properties. In this study, we prepared
      fifteen novel coumarin-bearing imidazolium and benzimidazolium chloride, nine
      novel benzoxazinone-bearing imidazolium and benzimidazolium chloride derivatives
      and evaluated their hCA inhibitory activities and along with fourteen previously
      synthesized derivatives we scanned their anticonvulsant effects. As all compounds
      inhibited purified hCA isoforms I and II, some of them also proved protective
      against Maximal electroshock seizure (MES) and ScMet induced seizures in mice.
      Molecular docking studies with selected coumarin derivatives have revealed that
      these compounds bind to the active pocket of the enzyme in a similar fashion to
      that previously described for coumarin derivatives. 

PMID- 26207514
TI  - The effects of some avermectins on bovine carbonic anhydrase enzyme.
AB  - Avermectins are effective agricultural pesticides and antiparasitic agents that
      are widely employed in the agricultural, veterinary and medical fields. The aim
      of this study was to investigate the inhibitory effects of selected avermectins
      including abamectin, doramectin, emamectin, eprinomectin, ivermectin and
      moxidectin that are used as drugs against a wide variety of internal and external
      mammalian parasites, on the carbonic anhydrase enzyme (CA, EC 4.2.1.1.) purified
      from fresh bovine erythrocyte. CA catalyses the rapid interconversion of carbon
      dioxide (CO2) and water (H2O) to bicarbonate ([Formula: see text]) and protons
      (H(+)) and regulate the acidity of the local tissues. Bovine erythrocyte CA (bCA)
      enzyme was purified by Sepharose-4B affinity chromatography with a yield of
      21.96% and 262.7-fold purification. The inhibition results obtained from this
      study showed Ki values of 9.73, 17.39, 20.43, 13.39, 16.44 and 17.73 nM for
      abamectin, doramectin, emamectin, eprinomectin, ivermectin and moxidectin,
      respectively. However, acetazolamide, well-known clinically established CA
      inhibitor, possessed a Ki value of 27.68 nM. 

PMID- 26207515
TI  - Parents' Challenges and Physicians' Tasks in Disclosing Cancer to Children. A
      Qualitative Interview Study and Reflections on Professional Duties in Pediatric
      Oncology.
AB  - BACKGROUND: Professional guidelines encourage physicians to provide children with
      as much information regarding their health as deemed developmentally and
      emotionally appropriate. However, empirical research indicates that in clinical
      practice, an open discussion with children about cancer is often lacking. This
      study explores impeding factors to and possible strategies for open communication
      of cancer diagnosis to children from the perspectives of parents and physicians.
      PROCEDURE: Semi-structured interviews were conducted with 18 parents of children
      with cancer and 10 treating oncologists. The patient sample was obtained from
      three pediatric units in Romania. Interviews were transcribed verbatim and
      interpreted using thematic analysis. Inductive open-coding procedures identified
      participants' accounts regarding their experiences with cancer diagnosis and
      treatment. Final themes were selected by grouping codes that formed a pattern in
      the data. RESULTS: An interplay of mainly three different factors-information
      overload and emotional turmoil, lack of knowledge and skills for disclosing the
      diagnosis, and assumptions about burdening the child when discussing cancer
      restricted parent-patient communication and subsequently affected physician
      patient exchanges. Oncologists recommended open communication at diagnosis, but
      left the final decision to the parents. They adapted their communication style
      with patients to parents' preference. CONCLUSIONS: Although physicians need to
      respect the wishes of children's legal representatives, they also have a duty to
      promote patients' best interests. We recommend that physicians employ a proactive
      stance in ensuring that children with cancer are appropriately informed about
      their diagnosis. In case of parents' arduous objections to full disclosure, an
      ethical consultation should be considered.

PMID- 26207516
TI  - Long noncoding RNA linc00617 exhibits oncogenic activity in breast cancer.
AB  - Protein-coding genes account for only 2% of the human genome, whereas the vast
      majority of transcripts are noncoding RNAs including long noncoding RNAs. LncRNAs
      are involved in the regulation of a diverse array of biological processes,
      including cancer progression. An evolutionarily conserved lncRNA TUNA, was found
      to be required for pluripotency of mouse embryonic stem cells. In this study, we
      found the human ortholog of TUNA, linc00617, was upregulated in breast cancer
      samples. Linc00617 promoted motility and invasion of breast cancer cells and
      induced epithelial-mesenchymal-transition (EMT), which was accompanied by
      generation of stem cell properties. Moreover, knockdown of linc00617 repressed
      lung metastasis in vivo. We demonstrated that linc00617 upregulated the
      expression of stemness factor Sox2 in breast cancer cells, which was shown to
      promote the oncogenic activity of breast cancer cells by stimulating epithelial
      to-mesenchymal transition and enhancing the tumor-initiating capacity. Thus, our
      data indicate that linc00617 functions as an important regulator of EMT and
      promotes breast cancer progression and metastasis via activating the
      transcription of Sox2. Together, it suggests that linc00617 may be a potential
      therapeutic target for aggressive breast cancer. (c) 2015 Wiley Periodicals, Inc.

PMID- 26207517
TI  - Cocrystal Transition Points: Role of Cocrystal Solubility, Drug Solubility, and
      Solubilizing Agents.
AB  - In this manuscript we bring together concepts that are relevant to the
      solubilization and thermodynamic stability of cocrystals in the presence of drug
      solubilizing agents. Simple equations are derived that allow calculation of
      cocrystal solubilization and transition point solubility. Analysis of 10
      cocrystals in 6 different solubilizing agents shows that cocrystal solubilization
      is quantitatively predicted from drug solubilization. Drug solubilizing agents
      such as surfactants and lipid-based media are also shown to induce cocrystal
      transition points, where drug and cocrystal solubilities are equal, and above
      which the cocrystal solubility advantage over drug is eliminated. We have
      discovered that cocrystal solubility at the transition point (S*) is independent
      of solubilizing agent, and can be predicted from knowledge of only the aqueous
      solubilities of drug and cocrystal. For 1:1 cocrystals, S* =
      (Scocrystal,aq)(2)/Sdrug,aq. S* is a key indicator of cocrystal thermodynamic
      stability and establishes the upper solubility limit below which cocrystal is
      more soluble than the constituent drug. These findings have important
      implications to tailor cocrystal solubility and stability in pharmaceutical
      formulations from commonly available drug solubility descriptors. 

PMID- 26207519
TI  - Rotational Spectrum, Conformational Composition, and Quantum Chemical
      Calculations of Cyanomethyl Formate (HC(O)OCH2C=N), a Compound of Potential
      Astrochemical Interest.
AB  - The rotational spectrum of cyanomethyl formate (HC(O)OCH2C=N) has been recorded
      in the 12-123 GHz spectral range. The spectra of two conformers were assigned.
      The rotamer denoted I has a symmetry plane and two out-of plane hydrogen atoms
      belonging to the cyanomethyl (CH2CN) moiety. In the conformer called II, the
      cyanomethyl group is rotated 80.3 degrees  out of this plane. Conformer I has an
      energy that is 1.4(6) kJ/mol lower than the energy of II according to relative
      intensity measurements. A large number of rotational transitions have been
      assigned for the ground and vibrationally excited states of the two conformers
      and accurate spectroscopic constants have been obtained. These constants should
      predict frequencies of transitions outside the investigated spectral range with a
      very high degree of precision. It is suggested that cyanomethyl formate is a
      potential interstellar compound. This suggestion is based on the fact that its
      congener methyl formate (HC(O)OCH3) exists across a large variety of interstellar
      environments and the fact that cyanides are very prevalent in the Universe. The
      experimental work has been augmented by high-level quantum chemical calculations.
      The CCSD/cc-pVQZ calculations are found to predict structures of the two forms
      that are very close to the Born-Oppenheimer equilibrium structures. MP2/cc-pVTZ
      predictions of several vibration-rotation interaction constants were generally
      found to be rather inaccurate. A gas-phase reaction between methyl formate and
      the cyanomethyl radical CH2CN to produce a hydrogen atom and cyanomethyl formate
      was mimicked using MP2/cc-pVTZ calculations. It was found that this reaction is
      not favored thermodynamically. It is also conjectured that the possible formation
      of cyanomethyl formate might be catalyzed and take place on interstellar
      particles.

PMID- 26207518
TI  - Opioids and breast cancer recurrence: A Danish population-based cohort study.
AB  - BACKGROUND: Opioids may alter immune function, thereby potentially affecting
      cancer recurrence. The authors investigated the association between postdiagnosis
      opioid use and breast cancer recurrence. METHODS: Patients with incident, early
      stage breast cancer who were diagnosed during 1996 through 2008 in Denmark were
      identified from the Danish Breast Cancer Cooperative Group Registry. Opioid
      prescriptions were ascertained from the Danish National Prescription Registry.
      Follow-up began on the date of primary surgery for breast cancer and continued
      until breast cancer recurrence, death, emigration, 10 years, or July 31, 2013,
      whichever occurred first. Cox regression models were used to compute hazard
      ratios and 95% confidence intervals associating breast cancer recurrence with
      opioid prescription use overall and by opioid type and strength,
      immunosuppressive effect, chronic use (>=6 months of continuous exposure), and
      cumulative morphine-equivalent dose, adjusting for confounders. RESULTS: In
      total, 34,188 patients were identified who, together, contributed 283,666 person
      years of follow-up. There was no association between ever-use of opioids and
      breast cancer recurrence (crude hazard ratio, 0.98; 95% confidence interval, 0.90
      1.1; adjusted hazard ratio, 1.0; 95% confidence interval, 0.92-1.1), regardless
      of opioid type, strength, chronicity of use, or cumulative dose. Breast cancer
      recurrence rates were lower among users of strongly (but not weakly)
      immunosuppressive opioids, possibly because of channeling bias among those with a
      high competing risk, because mortality was higher among users of this drug type.
      CONCLUSIONS: This large, prospective cohort study provided no clinically relevant
      evidence of an association between opioid prescriptions and breast cancer
      recurrence. The current findings are important to cancer survivorship, because
      opioids are frequently used to manage pain associated with comorbid conditions.

PMID- 26207520
TI  - Designing and evaluating a persuasive child restraint television commercial.
AB  - OBJECTIVE: Relatively high rates of child restraint inappropriate use and misuse
      and faults in the installation of restraints have suggested a crucial need for
      public education messages to raise parental awareness of the need to use
      restraints correctly. This project involved the devising and pilot testing of
      message concepts, filming of a television advertisement (the TVC), and the
      evaluation of the TVC. This article focuses specifically upon the evaluation of
      the TVC. The development and evaluation of the TVC were guided by an extended
      theory of planned behavior that included the standard constructs of attitudes,
      subjective norms, and perceived behavioral control as well as the additional
      constructs of group norms and descriptive norms. The study also explored the
      extent to which parents with low and high intentions to self-check restraints
      differed on salient beliefs regarding the behavior. METHODS: An online survey of
      parents (N = 384) was conducted where parents were randomly assigned to either
      the intervention group (n = 161), and therefore viewed the advertisement within
      the survey, or the control group (n = 223), and therefore did not view the
      advertisement. RESULTS: Following a one-off exposure to the TVC, the results
      indicated that, although not a significant difference, parents in the
      intervention group reported stronger intentions (M = 4.43, SD = 0.74) to self
      check restraints than parents in the control group (M = 4.18, SD = 0.86). In
      addition, parents in the intervention group (M = 4.59, SD = 0.47) reported
      significantly higher levels of perceived behavioral control than parents in the
      control group (M = 4.40, SD = 0.73). The regression results revealed that, for
      parents in the intervention group, attitudes and group norms were significant
      predictors of parental intentions to self-check their child restraint. Finally,
      the exploratory analyses of parental beliefs suggested that those parents with
      low intentions to self-check child restraints were significantly more likely than
      high intenders to agree that they did not have enough time to check restraints or
      that having a child in a restraint is more important than checking the
      installation of the restraint. CONCLUSION: Overall, the findings provide some
      support for the persuasiveness of the child restraint TVC and provide insight
      into the factors influencing reported parental intentions as well as salient
      beliefs underpinning self-checking of restraints. Interventions that attempt to
      increase parental perceptions of the importance of self-checking restraints
      regularly and brevity of the time involved in doing so may be effective.

PMID- 26207526
TI  - Similarity Mapplet: Interactive Visualization of the Directory of Useful Decoys
      and ChEMBL in High Dimensional Chemical Spaces.
AB  - An Internet portal accessible at www.gdb.unibe.ch has been set up to
      automatically generate color-coded similarity maps of the ChEMBL database in
      relation to up to two sets of active compounds taken from the enhanced Directory
      of Useful Decoys (eDUD), a random set of molecules, or up to two sets of user
      defined reference molecules. These maps visualize the relationships between the
      selected compounds and ChEMBL in six different high dimensional chemical spaces,
      namely MQN (42-D molecular quantum numbers), SMIfp (34-D SMILES fingerprint),
      APfp (20-D shape fingerprint), Xfp (55-D pharmacophore fingerprint), Sfp (1024
      bit substructure fingerprint), and ECfp4 (1024-bit extended connectivity
      fingerprint). The maps are supplied in form of Java based desktop applications
      called "similarity mapplets" allowing interactive content browsing and linked to
      a "Multifingerprint Browser for ChEMBL" (also accessible directly at
      www.gdb.unibe.ch ) to perform nearest neighbor searches. One can obtain six
      similarity mapplets of ChEMBL relative to random reference compounds, 606
      similarity mapplets relative to single eDUD active sets, 30,300 similarity
      mapplets relative to pairs of eDUD active sets, and any number of similarity
      mapplets relative to user-defined reference sets to help visualize the structural
      diversity of compound series in drug optimization projects and their relationship
      to other known bioactive compounds.

PMID- 26207521
TI  - B cells expressing CD11b effectively inhibit CD4+ T-cell responses and ameliorate
      experimental autoimmune hepatitis in mice.
AB  - Increasing evidence in recent years has suggested that B cells act as a crucial
      regulator in autoimmune diseases. However, little is known about their role in
      autoimmune hepatitis (AIH) and the underlying regulatory mechanisms. In this
      study, we show that B cells ameliorated experimental AIH (EAH) by suppressing
      CD4+ T-cell responses and that CD11b expression on B cells was required for the
      regulatory function of B cells. In vitro studies reveal that the suppressive
      function of CD11b was mediated by the impairment of T-cell antigen receptor (TCR)
      signaling transduction and the promotion of TCR down-regulation. Moreover, we
      show that the increased CD11b expression on B cells was interleukin (IL)-10
      dependent and that additional IL-10 stimulation promoted CD11b expression on B
      cells, thereby enhancing B-cell regulatory effects. CONCLUSION: These findings
      reveal a previously unrecognized role for CD11b in B-cell regulatory function and
      its protective effect on EAH.

PMID- 26207527
TI  - Impact of introduction of an acute surgical unit on management and outcomes of
      small bowel obstruction.
AB  - BACKGROUND: The acute surgical unit (ASU) is a recently established model of care
      in Australasia and worldwide. Limited data are available regarding its effect on
      the management of small bowel obstruction. We compared the management of small
      bowel obstruction before and after introduction of ASU at a major tertiary
      referral centre. We hypothesized that introduction of ASU would correlate with
      improved patient outcomes. METHODS: A retrospective review of prospectively
      maintained databases was performed over two separate 2-year periods, before and
      after the introduction of ASU. Data collected included demographics, co-morbidity
      status, use of water-soluble contrast agent and computed tomography. Outcome
      measures included surgical intervention, time to surgery, hospital length of
      stay, complications, 30-day readmissions, use of total parenteral nutrition,
      intensive care unit admissions and overall mortality. RESULTS: Total emergency
      admissions to the ASU increased from 2640 to 4575 between the two time periods. A
      total of 481 cases were identified (225 prior and 256 after introduction of ASU).
      Mortality decreased from 5.8% to 2.0% (P = 0.03), which remained significant
      after controlling for confounders with multivariate analysis (odds ratio = 0.24,
      95% confidence interval 0.08-0.73, P = 0.012). The proportion of surgically
      managed patients increased (20.9% versus 32.0%, P = 0.003) and more operations
      were performed within 5 days from presentation (76.6% versus 91.5%, P = 0.02).
      Fewer patients received water-soluble contrast agent (27.1% versus 18.4%, P =
      0.02), but more patients were investigated with a computed tomography (70.7%
      versus 79.7%, P = 0.02). CONCLUSION: The ASU model of care resulted in decreased
      mortality, shorter time to intervention and increased surgical management.
      Overall complications rate and length of stay did not change.

PMID- 26207528
TI  - Mycobacterium tuberculosis oriC sequestration by MtrA response regulator.
AB  - The regulators of Mycobacterium tuberculosis DNA replication are largely unknown.
      Here, we demonstrate that in synchronously replicating M. tuberculosis, MtrA
      access to origin of replication (oriC) is enriched in the post-replication (D)
      period. The increased oriC binding results from elevated MtrA phosphorylation
      (MtrA~P) as evidenced by reduced expression of dnaN, dnaA and increased
      expression of select cell division targets. Overproduction of gain-of-function
      MtrAY102C advanced the MtrA oriC access to the C period, reduced dnaA and dnaN
      expression, interfered with replication synchrony and compromised cell division.
      Overproduction of wild-type (MtrA+) or phosphorylation-defective MtrAD56N did not
      promote oriC access in the C period, nor affected cell cycle progression. MtrA
      interacts with DnaA signaling a possibility that DnaA helps load MtrA on oriC.
      Therefore, oriC sequestration by MtrA~P in the D period may normally serve to
      prevent untimely initiations and that DnaA-MtrA interactions may facilitate
      regulated oriC replication. Finally, despite the near sequence identity of MtrA
      in M. smegmatis and M. tuberculosis, the M. smegmatis oriC is not MtrA-target. We
      conclude that M. tuberculosis oriC has evolved to be regulated by MtrA and that
      cell cycle progression in this organisms are governed, at least in part, by
      oscillations in the MtrA~P levels. 

PMID- 26207530
TI  - Stigma, Attitudes, and Help-Seeking Intentions for Psychological Problems in
      Relation to Regional Suicide Rates.
AB  - In this ecological study, we investigated whether help-seeking related to stigma,
      intentions, and attitudes toward suicide are associated with the suicide rates of
      20 regions within the Netherlands and Belgium. Significant associations were
      found between regional suicide rates and the intention to seek informal help
      (beta = -1.47, p = .001), self-stigma (beta = 1.33, p = .038), and shame (beta =
      .71, p = .030). The association between self-stigma and suicide rate was mediated
      by intentions to seek informal help. These results suggest that to promote
      suicide prevention at the level of the regional population, stigma, shame, and
      intentions to seek help should be targeted in the public domain.

PMID- 26207529
TI  - Effect of Functionally Significant Deiodinase Single Nucleotide Polymorphisms on
      Drinking Behavior in Alcohol Dependence: An Exploratory Investigation.
AB  - BACKGROUND: Abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis have
      been reported in alcoholism; however, there is no definitive agreement on the
      specific thyroid abnormalities and their underlying mechanisms in alcohol
      dependence. The biological activity of thyroid hormones or the availability of T3
      is regulated by the three deiodinase enzymes: D1, D2, and D3. In the context of
      alcohol use, functionally significant single nucleotide polymorphisms (SNPs) of
      these deiodinase genes may play a role in HPT dysfunction. METHODS: This study
      explored the effect of three functionally significant SNPs (D1: rs2235544, D2:
      rs225014, and rs12885300) of deiodinase genes on drinking behavior and thyroid
      stimulating hormone (TSH) levels in alcohol-dependent (N = 521) and control
      subjects (N = 288). RESULTS: Rs225014 was associated with significant differences
      in the amount of naturalistic alcohol drinking assessed by Timeline Follow Back.
      Alcohol-dependent subjects had significantly higher TSH levels compared to
      controls; however, there was no effect of genotype on TSH levels for either
      group. CONCLUSIONS: These findings extend previous studies on thyroid dysfunction
      in alcoholism and provide novel, albeit preliminary, information by linking
      functionally significant genetic polymorphisms of the deiodinase enzymes with
      alcohol-drinking behavior.

PMID- 26207531
TI  - Estimated Exposure Risks from Carcinogenic Nitrosamines in Urban Airborne
      Particulate Matter.
AB  - Organic nitrogen (ON) compounds are present in atmospheric particulate matter
      (PM), but compared to their inorganic, hydrocarbon, and oxygenated counterparts,
      they are difficult to characterize due to their low concentrations in complex
      matrices. Nitrosamines are a class of ON compounds known to be highly
      carcinogenic and include species formed from nicotine degradation, but there are
      no detailed estimates of their abundance in ambient air. We use a highly
      sensitive analytical method, which is capable of separating over 700 ON
      compounds, to determine daily variability in nicotine, and 8 nonspecific and 4
      tobacco-specific nitrosamines in ambient PM from central London over two periods
      in winter and summer. The average total nitrosamine concentration was 5.2 ng m(
      3), substantially exceeding a current public recommendation of 0.3 ng m(-3) on a
      daily basis. The lifetime cancer risk from nitrosamines in urban PM exceeded the
      U.S. Environmental Protection Agency guideline of 1 excess cancer case per 1
      million population exposed after 1 h of exposure to observed concentrations per
      day over the duration of an adult lifetime. A clear relationship between ambient
      nitrosamines and total PM2.5 was observed with 1.9 ng m(-3) +/- 2.6 ng m(-3)
      (total nitrosamine) per 10 MUg m(-3) PM2.5.

PMID- 26207532
TI  - Multielectron oxidation in a ferromagnetically coupled dinickel(ii) triple
      mesocate.
AB  - Triple-stranded dinuclear nickel(ii) complexes of the meso-helicate type have
      been obtained from the new N,N'-1,3-phenylenebis(pyrazine-2-carboxamidate)
      ligand; they possess a multielectron redox behaviour featuring up to four
      stepwise, one-electron oxidation reactions of the two ferromagnetically coupled
      Ni(II) ions to afford the putative high-valent dinickel(iii) and dinickel(iv)
      species, as supported by theoretical calculations. 

PMID- 26207533
TI  - Etomidate-Induced Convulsions During Electroconvulsive Therapy: Two Case Reports.

PMID- 26207534
TI  - Index Electroconvulsive Therapy Course to Treat Severe Suicidality and Depression
      in Fahr Disease.

PMID- 26207535
TI  - Towards multifunctional lanthanide-based metal-organic frameworks.
AB  - We report the synthesis, structure and physicochemical attributes of a new
      holmium(III)-based metal-organic framework whose 3D network structure gives rise
      to porosity; the reported structure-type can be varied using a range of different
      lanthanide ions to tune the photophysical properties and produce ligand
      sensitised near-infrared (NIR) and visible light emitters.

PMID- 26207536
TI  - Questions From an Editor and Answers From an Accidental War Surgeon.

PMID- 26207537
TI  - A Comparative Study Between Deep Inferior Epigastric Artery Perforator and
      Thoracoacromial Venous Supercharged Deep Inferior Epigastric Artery Perforator
      Flaps.
AB  - BACKGROUND: Nowadays, microvascular breast reconstruction with abdominal
      perforator flap is a popular and widespread technique. However, venous congestion
      is a recurrent problem in deep inferior epigastric artery perforator (DIEP) flap
      survival. We present a venous supercharging technique using the thoracoacromial
      vein in DIEP free flap for breast reconstruction. METHODS: A prospective
      randomized study was conducted in 52 patients undergoing a free DIEP flap breast
      reconstruction. Classical DIEP flap using 1 venous anastomosis (DIEP group) was
      compared with thoracoacromial venous supercharged DIEP flap using the ipsilateral
      superficial epigastric vein as a supercharging vein (DIEP-TAsc group). The
      endpoint was to assess the equivalence or the superiority of each technique.
      Statistical analysis was made with the t test and the chi test. RESULTS: Venous
      congestion occurred in 16 (55.1%) patients in the DIEP group, and 3 (13%)
      patients in the DIEP-TAsc group (P = 0.001). The venous congestion rate was
      36.5%. Fat necrosis was experienced by 14 (48.2%) patients in the DIEP group, and
      4 (17.4%) patients in the DIEP-TAsc group (P = 0.020). The fat necrosis rate was
      34.6%. Partial flap necrosis occurred in 13 (44.8%) patients in the DIEP group,
      and 2 (8.7%) patients in the DIEP-TAsc group (P = 0.004). The partial flap
      necrosis rate was 28.8%. Total flap necrosis occurred in 5 (17.2%) patients in
      the DIEP group, but no (0%) patient in the DIEP-TAsc group (P = 0.036). The total
      flap necrosis rate was 9.6%. The mean operative time was 405 minutes (range, 355
      460) in the DIEP group, and 510 minutes (range, 405-590) in the DIEP-TAsc group
      (P < 0.001). CONCLUSIONS: Thoracoacromial venous supercharging using the
      ipsilateral superficial inferior epigastric vein is a valuable method which
      considerably secures the DIEP free flap in breast reconstruction although it
      lengthens the operative procedure. EBM level: Level III.

PMID- 26207538
TI  - Hilar Vessels of the Submandibular and Upper Jugular Neck Lymph Nodes: Anatomical
      Study for Vascularized Lymph Node Transfer to Extremity Lymphedema.
AB  - OBJECTIVES: Vascularized lymph node transfer for lymphedema is an emerging method
      of treatment. Vascularized lymph nodes have been harvested from a number of donor
      sites, that is, groin, axilla, and neck. There is a concern that harvesting nodes
      from the groin and axilla may lead to donor site lymphedema. This risk is greatly
      reduced in harvesting from the neck due to the abundant supply of lymph nodes
      here. In this cadaver study, we describe the submandibular and upper jugular
      groups of lymph nodes, demonstrate their hilar vessels, their source pedicles and
      drainage veins, quantified and qualified these groups of lymph nodes and their
      relationship to surrounding structures. METHODS: Five fresh adult cadaver necks
      (10 sides) were dissected looking at the submandibular and upper jugular neck
      nodes under the microscope. We carried out vascularized lymph node transfer of
      upper jugular nodes from the neck to the groin of 1 patient with stage II lower
      extremity lymphedema and transferred vascularized submandibular nodes from the
      neck to the upper arm in 1 patient with stage II upper extremity lymphedema.
      RESULTS: There was a mean of 3.2 (range, 1-5) lymph nodes in the submandibular
      group and a mean of 4.1 (range, 2-6) lymph nodes in the upper jugular group. The
      submandibular nodes were perfused by branches of the facial artery, that is,
      glandular and/or facial branches and/or submental artery in various permutations.
      The upper jugular nodes were perfused by the sternocleidomastoid artery, which
      branches from the superior thyroid artery (70%) or emerges directly from the
      external carotid artery (30%). Hilar veins were found to drain into surrounding
      larger draining tributary veins and ultimately into the internal jugular vein. At
      1-year follow-up, there was a considerable decrease in girth circumference in our
      patients, no episodes of cellulitis after surgery, with subjective improvement in
      limb heaviness and skin pliability. CONCLUSIONS: This knowledge of hilar blood
      supply will aid in transferring a lymphatic flap with intact microcirculation.
      When harvesting the submandibular nodes or upper jugular nodes, it is essential
      to harvest them based on their source pedicles, that is, facial artery and
      sternocleidomastoid artery, respectively, to supply live nodes to the recipient
      lymphedematous limb.

PMID- 26207539
TI  - Surgical Treatment and Recurrence of Cutaneous Nasal Malignancies: A 26-Year
      Retrospective Review of 1795 Patients.
AB  - Frequent localization of facial malignancies in the nasal area and their required
      complete surgical extirpation pose a significant challenge to the plastic
      surgeon, who is called to perform a suitable delicate reconstruction of produced
      nasal skin defects. The present study was aimed to examine the role of tumor
      characteristics in the prognosis of patients with nasal skin cancer undergoing
      surgical management.A retrospective review of 1795 patients operated on for nasal
      cutaneous neoplasms during a 26-year period is presented in our study.
      Descriptive statistics were appropriately calculated; multivariate Cox regression
      analysis was performed regarding the possible risk factors for recurrence. Only
      those with a complete follow-up were included in the study. The mean age of our
      study population was 66.7 years with a male majority (52.4%). Basal cell
      carcinoma appeared as the most common histological type (87.7%), followed by
      squamous cell carcinoma (7.9%); the latter correlated with poor prognosis.The
      nasal sidewalls were the most frequent lesion location (29.8%), followed by the
      alae (27.8%), dorsum (21.7%), and tip (19.3%). The columella was very rarely
      affected (0.5%) but was associated with increased recurrence [hazard ratio, 4.74;
      95% confidence interval (CI), 1.12-20.00; P = 0.034]. Most patients were treated
      with elliptical excision and direct closure (58.7%). Local flaps (31.0%) and skin
      grafting (9.0%) proved very reliable surgical options, especially for larger,
      high-risk lesions. Recurrence transpired in 46 patients (2.6%) and 4 skin cancer
      related deaths occurred.Surgical modality of choice should be individualized and
      carefully adjusted to patients' needs. Moreover, more elective techniques, such
      as Mohs micrographic surgery or cumulative therapeutic approaches, like
      irradiation, should be examined as a beneficial aid to confront high-risk
      malignancies. 

PMID- 26207540
TI  - Two-Stage Repair for Severe Proximal Hypospadias Using Oral Mucosal Grafts:
      Combination of a Modified Bracka Method and a Modified Byars Flap Method: Should
      Local Flaps be Used for Urethral Reconstruction in Hypospadias Repair?

PMID- 26207541
TI  - Reverse Superior Labial Artery Flap in Reconstruction of Nose and Medial Cheek
      Large Defects: Reply.

PMID- 26207542
TI  - The Divine Proportion "Ace of Spades" Umbilicoplasty: A New Method of Navel
      Positioning and Plasty in Abdominoplasty.
AB  - BACKGROUND: Achievement of a well-balanced positioned navel along the
      longitudinal axis with a pleasing shape and hidden scarring will have a
      tremendous impact on the overall cosmetic outcome of an abdominoplasty. In this
      era of navel display, piercing, and tattooing, an increasing attention is paid by
      people toward navel shape and position. However, in plastic surgery, there is no
      standardization regarding navel repositioning and plasty during abdominoplasty.
      The aim of this article is to describe the clinical translation of our
      observational study on navel surface anatomy by reporting our experience with a
      new umbilicoplasty technique. MATERIALS AND METHODS: Between July 2013 and March
      2014, 23 consecutive patients underwent elective deep inferior epigastric
      perforator free flap breast reconstruction. Patients' mean age was 45.5 years
      (range, 36-68 years). Ten patients were normal weight, 11 were overweight, and 2
      were class-1 obese. All 23 patients underwent the divine proportion ace of spade
      umbilicoplasty. RESULTS: Pleasant looking, depressed, and oval navels with
      superior hooding were successfully achieved. No infection or necrosis of the
      navel skin or abdominal skin flaps was experienced. Additionally, no scar
      constriction, navel distortion, or stenosis occurred. Postoperative results were
      graded as excellent in 8 cases (36%), very good in 12 (55%), and good in the 2
      cases (9%) with mildly hypertrophic scars. Patient satisfaction was high to very
      high. CONCLUSIONS: A Fibonacci caliper might aid in the proper positioning of the
      umbilicus on the abdominal wall avoiding an undesirable high- or low-riding
      navel. The "ace of spades" umbilicoplasty restores a natural-looking depressed
      navel with an oval shape and superior hooding.

PMID- 26207543
TI  - Breast Reconstruction After Solid Organ Transplant.
AB  - BACKGROUND: Solid organ transplant patients frequently develop posttransplant
      malignancies including breast cancer. They may desire breast reconstruction after
      mastectomy, which could potentially be complicated by their transplant status,
      immunosuppressive regimen, and previous operations. We review our experience with
      patients who have undergone solid organ transplant and subsequent breast
      reconstruction after mastectomy METHODS: After institutional review board
      approval, we queried our prospective breast reconstruction and solid organ
      transplant databases for corresponding patients. Inclusion criteria comprised
      breast reconstruction after solid organ transplant. A chart review was conducted
      of identified patients. RESULTS: Seventeen patients were identified: 1 pulmonary
      transplant, 4 cardiac transplants, 2 liver transplants, 1 pancreas transplant, 2
      combined kidney/pancreas transplants, and 7 kidney transplants. Indications for
      mastectomy included posttransplant malignancy and prophylaxis. Median time from
      transplant to completion of reconstruction was 186 months (range, 11-336 months).
      Median age at transplant was 34.5 years (range, 21-65 years) with the median age
      of the patients at reconstructive surgery 51.5 years (range, 34-71 years). Median
      body mass index was 25.3 (range, 21.3-46.5). No significant complications were
      noted after reconstructive surgery. All patients were on full immunosuppression
      at time of reconstruction. CONCLUSIONS: Breast reconstruction is a viable option
      for transplant patients after mastectomy and should not be refused based on their
      transplant status. Close coordination with the transplant team and careful
      preoperative planning is essential for optimal outcomes.

PMID- 26207544
TI  - A Novel Lymphaticovenular Anastomosis Rat Model.
AB  - INTRODUCTION: Lymphaticovenular anastomosis (LVA) has become an important
      procedure for the surgical treatment of lymphedema. In the past, the anatomy of
      the lymphatic system of animal models has been reported. However, to our
      knowledge, there have been few reports of animal models of LVA including training
      model. In this study, we report on a relatively simple and ideal animal LVA model
      based on peritoneal lymph ducts and veins. PATIENTS AND METHODS: For 10 rats,
      diameters of lumbar lymphatic ducts and iliolumbar veins in the peritoneal cavity
      on both sides were measured, and LVA was performed. In addition, we measured the
      diameters of 28 lymphatic ducts and veins in 8 patients who had previously
      undergone LVA and compared the results with those obtained in this rat model.
      RESULTS: The mean diameter of the lymphatic ducts was 0.61 mm, and the iliolumbar
      veins were 0.81 mm. On the other hand, the mean diameters of the 28 lymphatic
      ducts and veins of the 8 patients in whom we performed LVA were 0.58 and 0.76 mm,
      respectively. The differences in the diameters of the lymph vessels and veins
      between the rats and patients were not statistically significant. CONCLUSIONS: We
      report on an LVA model involving the use of the lumbar lymphatic duct and
      iliolumbar veins of rats. The diameter, nature, and placement of the anastomosis
      using this model are very similar to that noted during real human surgery. We
      believe that our rat model will be useful as a practical training model for LVA
      and in studies on postoperative changes in LVA.

PMID- 26207545
TI  - Improvement of Fat Transplantation: Fat Graft With Adipose-Derived Stem Cells and
      Oxygen-Generating Microspheres.
AB  - BACKGROUND: Autologous fat transplantation has become increasingly popular in
      plastic surgery. However, high resorption rate limits the utility of this
      technique. To address this problem, this study examined fat transplantation with
      oxygen-generating microspheres and adipose-derived stem cells (ASCs) in a rat
      model. METHODS: The rats were assigned to four groups. Group 1 had fat
      transplantation only; group 2, fat transplantation with oxygen-generating
      microspheres; group 3, fat transplantation with ASCs; group 4, fat
      transplantation with oxygen-generating microspheres and ASCs. RESULTS: At
      postoperative 2 weeks, compared to the control group, weight and volume increased
      significantly in groups 3 and 4. The survival distance of fat cells from the
      margin of transplanted tissue was 247 MUm in group 1, 379 MUm group 2, 521 MUm in
      group 3, and 669 MUm in group 4. All of the experimental groups were
      significantly increased. Growth factors (fibroblast growth factor- 2 [FGF-2],
      insulin-like growth factor-1, epidermal growth factor, and vascular endothelial
      growth factor) analysis was performed through real-time polymerase chain
      reaction. Compared to the control group, the mean of the periods was
      statistically significant at FGF-2 in group 3 and FGF-2, insulin-like growth
      factor-1, and epidermal growth factor in group 4. CONCLUSIONS: In this study, fat
      transplantation was improved with oxygen-generating microspheres and ASCs. The
      oxygen-generating microspheres supply oxygen to adipocytes and ASCs where
      diffusion does not occur, increasing cell survival rate. Surviving ASCs become
      involved in the metabolic processes for adipocytes and induce angiogenesis.
      Therefore, fat transplantation result was improved. Excessive oxygen supply,
      however, reduces angiogenesis and may cause oxygen toxicity. So, further
      evaluation of oxygen-generating microspheres is necessary for application to
      tissues to determine appropriate oxygen concentration and a valid oxygen release
      period.

PMID- 26207546
TI  - Facial Artery Perforator and Depressor Anguli Oris Muscle Chimeric Flap: A New
      Design of an Old Flap.
AB  - BACKGROUND: The aim of this study was to investigate the reliability and outcomes
      of the facial artery perforator and separately elevated depressor anguli oris
      (DAO) muscle chimeric flap for the reconstruction of partial or total lower lip
      defects. METHODS: Eleven patients with malignant skin tumors located at the lower
      lip were operated between 2013 and 2015. After the excision of the tumor with
      adequate clear margins using margin controlled excision technique, an appropriate
      flap fitting to the resultant defect based on the perforators of the facial
      artery and DAO muscle was prepared and placed into the defect. The DAO muscle
      activity was tested with electromyography in the postoperative first year
      examination. RESULTS: Besides 1 patient with transient venous insufficiency, all
      the flaps healed well without a partial or total flap loss. The mean follow-up
      period was 10 months. No new primary tumor or recurrence was observed. Although
      in 1 patient, transient asymmetric smiling and mild drooling was observed, the
      overall oral competence results were found to be quite satisfactory. The
      electromyography evaluation of DAO muscle of 5 patients who reached the
      postoperative first year examination showed action potential results in normal
      limits with a slight decrease. All patients were satisfied with the final
      esthetic and functional result. CONCLUSIONS: The facial artery perforator and
      depressor angel oris muscle chimeric flap is a valuable option for reconstruction
      of lower lip defects providing esthetically and functionally good results.

PMID- 26207547
TI  - The Difficult Surgeon.

PMID- 26207548
TI  - Reverse Superior Labial Artery Flap in Reconstruction of Nose and Medial Cheek
      Large Defects.

PMID- 26207549
TI  - Reduction Malarplasty With Face-Lift for Older Asians With Prominent Zygoma.
AB  - BACKGROUND: In Asian culture, overly prominent zygomas are undesirable because
      they give a masculine and severe appearance. Thus, reduction malarplasty is now
      becoming one of the most popular procedures among Asian women. However, older
      patients present sagging facial soft tissue and have high incidence of cheek
      descent after surgery. To overcome these issues and achieve better cosmetic
      surgical outcomes, we performed a reduction malarplasty combined with a face-lift
      to achieve an oval and youthful midface. METHODS: It was a retrospective
      observational study of 22 older Asian women who complained of prominent zygoma
      and aged midface. All of them had undergone reduction malarplasty combined with
      cheek-lift. Clinical results were assessed with photographs and patient
      satisfactory rates. RESULTS: The L-shaped reduction malarplasty with face-lift
      was performed successfully in all cases. All of the patients recover successfully
      without major complications. Malar prominence and midface aging was improved, and
      the natural midface contour was preserved. One hundred percent of the patients
      thought that the shape of their midface had improved, and 95.5% were satisfied
      with the rejuvenation of midface. CONCLUSIONS: The reduction malarplasty combined
      with face-lift effectively addressed the malar prominence and midface aging
      issues simultaneously. Therefore, this can be a useful technique to restore the
      youthful and proportionate facial relationships in older Asian patients.

PMID- 26207550
TI  - Multilayered Flap Technique: A Method for Delayed Closure of Giant Omphalocele.
AB  - Giant omphalocele is a rare, large abdominal wall defect in which the intra
      abdominal organs herniate through the umbilical cord and are covered by a sac.
      Surgical management of giant omphalocele is challenging, and optimal treatment
      remains controversial. Two generally accepted treatment options are staged
      closure and delayed closure. Delayed closure takes place after a period of
      conservative treatment promoting omphalocele sac epithelialization. We present 3
      patients treated by a delayed closure technique for ventral hernia repair. In
      this technique, the epithelialized omphalocele sac and peritoneum are elevated as
      flaps, which are used to reconstruct the abdominal wall in multiple layers. 

PMID- 26207551
TI  - Maxillomandibular Fixation by Plastic Surgeons: Cost Analysis and Utilization of
      Resources.
AB  - PURPOSE: Maxillomandibular fixation (MMF) can be performed using various
      techniques. Two common approaches used are arch bars and bone screws. Arch bars
      are the gold standard and inexpensive, but often require increased procedure
      time. Bone screws with wire fixation is a popular alternative, but more expensive
      than arch bars. The differences in costs of care, complications, and operative
      times between these 2 techniques are analyzed. METHODS: A chart review was
      conducted on patients treated over the last 12 years at our institution. Forty
      four patients with CPT code 21453 (closed reduction of mandible fracture with
      interdental fixation) with an isolated mandible fracture were used in our data
      collection. The operating room (OR) costs, procedure duration, and complications
      for these patients were analyzed. RESULTS: Operative times were significantly
      shorter for patients treated with bone screws (P < 0.002). The costs for one trip
      to the OR for either method of fixation did not show any significant differences
      (P < 0.840). More patients with arch bar fixation (62%) required a second trip to
      the OR for removal in comparison to those with screw fixation (31%) (P < 0.068).
      This additional trip to the OR added significant cost. There were no differences
      in patient complications between these 2 fixation techniques. CONCLUSIONS: The
      MMF with bone screws represents an attractive alternative to fixation with arch
      bars in appropriate scenarios. Screw fixation offers reduced costs, fewer trips
      to the OR, and decreased operative duration without a difference in
      complications. Cost savings were noted most significantly in a decreased need for
      secondary procedures in patients who were treated with MMF screws. Screw fixation
      offers potential for reducing the costs of care in treating patients with
      minimally displaced or favorable mandible fractures.

PMID- 26207553
TI  - Functional Donor Site Morbidity After Vascularized Toe Transfer Procedures: A
      Review of the Literature and Biomechanical Consideration for Surgical Site
      Selection.
AB  - BACKGROUND: The purpose of this study was to conduct a systematic review and
      pooled analysis of vascularized toe-to-hand transfer to determine functional
      donor site morbidity among different techniques. METHODS: Pubmed MEDLINE, EMBASE,
      and Cochrane databases search yielded 302 citations, with 56 meeting inclusion
      criteria. Pooled outcomes and analysis are reported based on donor site
      morbidity, specific toe transferred, technique used, and foot biomechanical
      changes. RESULTS: A total of 802 digit transfers (418 isolated great toe
      transfers, 324 isolated second toe transfers, and 153 toes classified as "other")
      were included for analysis. Sex was reported in 510 patients (80.2 % men, 19.8%
      women). The mean patient age was 28.5 +/- 8.4 years. Functional impairment
      analysis found 23.7% (97 digit transfers) experienced gait impairment. Great toe
      transfer versus second toe transfer versus the "other" group demonstrated
      morbidity rates of 21.8%, 14.5%, and 23% (P = 0.001), respectively. Donor site
      reoperative intervention occurred in 11.8% of cases (95 digits): 4.5%, 16.6%, and
      16.0% (P < 0.001), respectively. Mean follow-up time was 62.6 months.
      CONCLUSIONS: Functional foot impairment can occur after various toe transfer
      procedures due to altered biomechanics of weight distribution and gait. Rigorous
      biomechanical foot evaluation of this subset of patients is lacking. Great toe
      transfer appears to have the highest morbidity rate, but lower reoperative
      intervention as compared to second toe transfer. Preserving ray projection does
      not prevent biomechanical changes to the foot, but may delay functional
      impairment leading to favorable functional interpretation by patients and
      surgeons.

PMID- 26207554
TI  - Autologous Fat Grafting to the Breast Using REVOLVE System to Reduce Clinical
      Costs.
AB  - BACKGROUND: With the increasing popularity of fat grafting over the past decade,
      the techniques for harvest, processing and preparation, and transfer of the fat
      cells have evolved to improve efficiency and consistency. The REVOLVE System is a
      fat processing device used in autologous fat grafting which eliminates much of
      the specialized equipment as well as the labor intensive and time consuming
      efforts of the original Coleman technique of fat processing. This retrospective
      study evaluates the economics of fat grafting, comparing traditional Coleman
      processing to the REVOLVE System. METHODS: From June 2013 through December 2013,
      88 fat grafting cases by a single-surgeon were reviewed. Timed procedures using
      either the REVOLVE System or Coleman technique were extracted from the group.
      Data including fat grafting procedure time, harvested volume, harvest and
      recipient sites, and concurrent procedures were gathered. Cost and utilization
      assessments were performed comparing the economics between the groups using
      standard values of operating room costs provided by the study hospital. RESULTS:
      Thirty-seven patients with timed procedures were identified, 13 of which were
      Coleman technique patients and twenty-four (24) were REVOLVE System patients. The
      average rate of fat transfer was 1.77 mL/minute for the Coleman technique and
      4.69 mL/minute for the REVOLVE System, which was a statistically significant
      difference (P < 0.0001) between the 2 groups. Cost analysis comparing the REVOLVE
      System and Coleman techniques demonstrates a dramatic divergence in the price per
      mL of transferred fat at 75 mL when using the previously calculated rates for
      each group. CONCLUSIONS: This single surgeon's experience with the REVOLVE System
      for fat processing establishes economic support for its use in specific high
      volume fat grafting cases. Cost analysis comparing the REVOLVE System and Coleman
      techniques suggests that in cases of planned fat transfer of 75 mL or more, using
      the REVOLVE System for fat processing is more economically beneficial. This study
      may serve as a guide to plastic surgeons in deciding which cases might be
      appropriate for the use of the REVOLVE System and is the first report comparing
      economics of fat grafting with the traditional Coleman technique and the REVOLVE
      System.

PMID- 26207555
TI  - Clinical Safety of Stromal Vascular Fraction Separation at the Point of Care.
AB  - INTRODUCTION: Pluripotential cells in adipose tissue may be important in long
      term volume retention and regenerative effects of fat grafting. Unfortunately,
      graft harvest with lipoaspiration significantly depletes the population of
      stromal vascular cells, which includes adipose stem cells. Stromal vascular
      fraction (SVF) cells may be isolated from excess lipoaspirate at the point of
      care and used to replenish fat grafts, a technique termed cell-assisted
      lipotransfer (CAL). Preclinical and clinical evidence supports the rationale of
      CAL but clinical adoption of the strategy requires evidence of clinical safety.
      This prospective, level 1 study reports clinical safety of SVF-enhanced fat
      grafting using a manual, collagenase-based separation process to isolate
      autogenous progenitor cells from lipoaspirate at the point of care. METHODS: One
      hundred sixty-four subjects underwent 174 SVF-enhanced autologous fat grafting
      procedures at the university stem cell center between August 2009 and November
      2014 for a variety of cosmetic and reconstructive indications. RESULTS: Cell
      assisted lipotransfer was performed for a variety of cosmetic and reconstructive
      indications. The mean time of the SVF isolation process was 91 minutes. Because
      of the frequent concomitant procedures, the average operating room time increased
      by only 11 minutes. Mean follow-up was 19.9 months. There were no major
      complications and 6 minor complications. No collagenase or neutral protease
      related complications were observed. CONCLUSIONS: This series of 174 CAL cases
      demonstrates that SVF cell isolation using a standardized, manual, collagenase
      based process at the POC is equivalent in safety compared to nonenhanced fat
      grafting. These results support expanded use of CAL in the clinical research
      setting.

PMID- 26207556
TI  - The Effects of Hydrogen Sulfide on Adipocyte Viability in Human Adipocyte and
      Adipocyte-Derived Mesenchymal Stem Cell Cultures Under Ischemic Conditions.
AB  - BACKGROUND: This study evaluated the in vitro effects of hydrogen sulfide on
      adipocyte survival under ischemic conditions and explored possible mechanisms of
      its apoptotic process. METHODS: The mesenchymal stem cell culture was prepared
      from a human subcutaneous adipose tissue sample. Adipose-derived mesenchymal stem
      cells were differentiated into the adipogenic direction, and a mature adipocyte
      culture was obtained. The adipose-derived mesenchymal stem cell and mature
      adipocyte cultures were both divided into 6 groups. Sodium hydrogen sulfide was
      used as a hydrogen sulfide donor. After treating the groups with sodium hydrogen
      sulfide (0, 0.1, 1, 10, 100, and 1000 MUM), the cell cultures were incubated in
      1% oxygen at 37 degrees C for 24 hours. After the ischemia period, the cell
      culture groups were evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide test for the proliferation/cytotoxicity rates, flow
      cytometry for apoptosis and necrosis rates, and reverse transcriptase polymerase
      chain reaction for apoptotic (Bax, Caspase-3) and antiapoptotic (Bcl-2) gene
      expression levels. RESULTS: Statistically significant increases in proliferation
      rates were found in mesenchymal stem cell groups treated with low dose (0, 1, and
      1 MUM) sodium hydrogen sulfide (P<0.05). For each dose, a statistically
      significant decrease was found in late apoptosis levels on the mature adipocyte
      cultures (P<0.05). In both cell culture groups, Bcl-2 gene expression was
      increased and Caspase-3 gene expression was decreased. CONCLUSIONS: Under
      ischemic conditions, hydrogen sulfide has a protective effect on mesenchymal stem
      cells and mature adipocytes, and this effect is mediated by the elevation of
      antiapoptotic gene expression.

PMID- 26207557
TI  - How "Low-Level" Evidence Has Changed Plastic Surgery: Time to Appreciate the
      Value of Case Reports and Case Series.

PMID- 26207558
TI  - Landmarks for Sacral Debridement in Sacral Pressure Sores.
AB  - INTRODUCTION: Most cases of sacral osteomyelitis arising in the setting of sacral
      pressure ulcers require minimal cortical debridement. When faced with advanced
      bony involvement, the surgeon is often unclear about how much can safely be
      resected. Unfamiliarity with sacral anatomy can lead to concerns of inadvertent
      entry into the dural space and compromise of future flap options. MATERIALS AND
      METHODS: A cadaveric study (n = 6), in which a wide posterior dissection of the
      sacrum, was performed. Relationships of the dural sac to bony landmarks of the
      posterior pelvis were noted. RESULTS: The termination of the dural sac was found
      in our study to occur at the junction of S2/S3 vertebral bodies, which was
      located at a mean distance of 0.38 +/- 0.16 cm distal to the inferior-most extent
      of the posterior superior iliac spine (PSIS). The mean thickness of the posterior
      table of sacrum at this level was 1.7 cm at the midline and 0.5 cm at the sacral
      foramina. CONCLUSIONS: The PSIS is a reliable landmark for localizing the S2/S3
      junction and the termination of the dural sac. Sacral debridement medial to the
      sacral foramina above the level of PSIS must be conservative whenever possible.
      If aggressive debridement is necessary above this level, the surgeon must be
      alert to the possibility of dural involvement.

PMID- 26207559
TI  - The Discrete Scar in Prominent Ear Correction: A Digital 3-Dimensional Analysis
      to Determine the Ideal Incision for Otoplasty.

PMID- 26207560
TI  - A Novel Hypothesis of Visual Loss Secondary to Cosmetic Facial Filler Injection.
AB  - With the current tendency of increasing minimally invasive cosmetic surgeries,
      some rare but disastrous complications of facial filler injections come into
      sight, such as visual loss. The study aims to investigate the possible route that
      the injected droplet accesses the ophthalmic artery to explain and prevent such
      devastating complications. We searched the National Library of Medicine's PubMed
      database for cases of visual loss secondary to cosmetic facial filler injection,
      and reviewed relevant case reports/surveys, as well as accompanying references.
      Data obtained were analyzed, with special interest in injected sites and filler
      material, and clinical features of visual loss. Based on the anatomy of facial
      vessels, we inferred the possible route of injected droplet migrating from
      injection sites to ophthalmic artery. Most physicians propose a retrograde
      embolic mechanism, but the culprit artery when injecting different sites is not
      determined. We consider accidentally breaking into supraorbital artery or
      supratrochlear artery may cause occlusion of ophthalmic artery when injecting
      into glabella or forehead region. Speaking of the nasolabial fold and nasal
      dorsum region, any injections in the anastomosis of the dorsal nasal artery,
      angular artery, and lateral nasal artery can lead to retrograde embolism.
      Similarly, in the temporal region, we believe there is abnormal anastomosis
      between frontal branch of superficial temporal artery from external carotid
      artery and supraorbital artery from ophthalmic artery. In our hypothesis, we can
      explain the accompanying brain infarction after iatrogenic visual loss. If the
      injecting pressure is forceful enough, it may push the embolic materials into
      middle cerebral artery. Although iatrogenic ophthalmic artery occlusion is a rare
      complication after the facial filler injection surgery, it is usually
      devastating. Both the patient and the surgeon should be aware of the risk of
      irreversible blindness. Ideally, the injection sites should avoid the small
      vessels nearby, the injecting force and velocity should be as gentle and slow as
      possible. 

PMID- 26207562
TI  - Osteoectomy in Rhinoplasty: A New Concept in Nasal Bones Repositioning.
AB  - BACKGROUND: Modern techniques of osteotomy have evolved to take into account the
      effects of bony repositioning on functional as well as aesthetic outcomes.
      Although a variety of methods have been described to appropriately mobilize and
      reposition the bony nasal vault, there is still no single procedure that can
      successfully manage nasal bones in its entirety. MATERIAL AND METHODS: We present
      the bone chisel scraping osteoectomy technique for lateral and medial osteotomies
      with the aim of managing nasal bone deformities that can overcome diverse
      shortcomings of the conventional methods. The new operative method was performed
      in 184 nasal bone osteoectomies (92 patients, 22 men and 70 women), ranging in
      age from 18 to 69 years (mean age, 38 years). The functional results were
      evaluated postoperatively by the Nasal Obstruction Symptom Evaluation scale, a
      brief and easy to complete validated questionnaire with a final score grading
      from 0 to 100 at 3 and 6 months postoperatively. RESULTS: With this new approach,
      no functional problems were reported. The mean Nasal Obstruction Symptom
      Evaluation scale score was 5.3 at 3 months and 1.9 at 6 months. Only 1 primary
      case was reoperated for open roof deformity. Comparing the results with the
      previous osteotomy series of the senior author osteoectomy and osteotomy revision
      rates for inadequate bone mobilization were similar but osteoectomy technique did
      not create functional problems as the osteotomy technique did. CONCLUSIONS:
      Although this technique prolongs the operating time, it could offer considerable
      advantages in comparison with the classical techniques using osteotomies and
      hammer. This is because it offers a greater respect to the nasal respiratory
      function and gives a much better nasal base width control, resulting in more
      predictable results, less trauma, and therefore a lower risk of postoperative
      complications.

PMID- 26207563
TI  - Cervical cancer screening in immigrant women in Italy: a survey on participation,
      cytology and histology results.
AB  - Cervical cancer screening programmes in Italy actively invite all 25-64-year-old
      resident women for the Pap test every 3 years irrespective of their citizenship.
      Immigrant women come from countries where screening is absent or poorly
      implemented and the prevalence of human papillomavirus is often high. These women
      therefore have significant risk factors for cervical cancer. The Italian Group
      for Cervical Cancer Screening promoted a survey of all the screening programmes
      on the participation and the positivity and detection rates in Italian and
      foreign women in 2009-2011. Aggregated data for participation, cytology results,
      compliance with colposcopy and histology results were collected, distinguishing
      between women born in Italy and abroad. All comparisons were age adjusted. Forty
      eight programmes out of 120 participated in the immigrant survey, with 3 147 428
      invited and 1 427 412 screened Italian women and 516 291 invited and 205 948
      screened foreign women. Foreign women had a slightly lower participation rate
      compared with Italians (39.9 vs. 45.4%), whereas compliance with colposcopy was
      similar (90%). Foreigners showed a higher risk of pathological findings than
      Italians: cytology positivity [relative risk (RR)=1.25, 95% confidence interval
      (CI) 1.24-1.27] and detection rate for cervical intraepithelial neoplasia grade 2
      (CIN2) (RR=1.39, 95% CI 1.31-1.47), CIN3 (RR=2.07, 95% CI 1.96-2.18) and cancer
      (RR=2.68, 95% CI 2.24-3.22). The ratio between cancer and CIN was higher in
      immigrants (0.06 vs. 0.04, P<0.01). Foreign women had a higher risk of cervical
      precancer and cancer. Because of their high risk and because opportunistic
      screening does not cover this often disadvantaged group, achieving high
      participation in screening programmes for foreigners is critical to further
      reducing the cervical cancer burden in Italy.

PMID- 26207564
TI  - Mechanistic understanding of CoO-catalyzed hydrogen desorption from a LiBH4.NH3
      3LiH system.
AB  - Addition of a minor quantity of CoO significantly reduces the dehydrogenation
      temperature, accelerates the dehydrogenation rate and increases the hydrogen
      purity of the LiBH4.NH3-3LiH system. The LiBH4.NH3-3LiH-0.1CoO sample exhibits
      optimal dehydrogenation properties because it releases 8.5 wt% of hydrogen below
      250  degrees C, which is approximately 90  degrees C lower than that of the
      pristine sample. At 200  degrees C, approximately 8.0 wt% of hydrogen is released
      from the LiBH4.NH3-3LiH-0.1CoO sample within 100 min, whereas only 4.1 wt% is
      released from the pristine sample under identical conditions. The EXAFS analyses
      reveal that upon heating, CoO is first reduced to metallic Co at 130  degrees C
      and then partially combines with B to form a Co-B species. The in situ formed Co
      and Co-B are finely dispersed in the dehydrogenated intermediates, and they play
      critical roles as active catalysts in favour of breaking the B-H bonds of the Li
      B-N-H species. This effectively decreases the thermodynamic and kinetic barriers
      of the dehydrogenation reaction of the LiBH4.NH3-3LiH system. 

PMID- 26207565
TI  - Tissue distribution of pretomanid in rat brain via mass spectrometry imaging.
AB  - 1. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI
      MSI) combines the sensitivity and selectivity of mass spectrometry with spatial
      analysis to provide a new dimension for histological analyses of the distribution
      of drugs in tissue. Pretomanid is a pro-drug belonging to a class of antibiotics
      known as nitroimidizoles, which have been proven to be active under hypoxic
      conditions and to the best of our knowledge there have been no studies
      investigating the distribution and localisation of this class of compounds in the
      brain using MALDI MSI. 2. Herein, we report on the distribution of pretomanid in
      the healthy rat brain after intraperitoneal administration (20 mg/kg) using MALDI
      MSI. Our findings showed that the drug localises in specific compartments of the
      rat brain viz. the corpus callosum, a dense network of neurons connecting left
      and right cerebral hemispheres. 3. This study proves that MALDI MSI technique has
      great potential for mapping the pretomanid distribution in uninfected tissue
      samples, without the need for molecular labelling.

PMID- 26207566
TI  - Repeat sentinel lymph node biopsy in patients with ipsilateral recurrent breast
      cancer after breast-conserving therapy and negative sentinel lymph node biopsy: a
      prospective study.
AB  - BACKGROUND: Patients with ipsilateral breast tumor recurrence or new ipsilateral
      primary tumor after previous breast conservative surgery with negative sentinel
      lymph node biopsy need a new axillary staging procedure. However, the best
      surgical option, i.e. repeat sentinel lymph node biopsy or axillary lymph node
      dissection, is still debated. Purpose of the study is to assess the performance
      of repeat sentinel lymph node biopsy. METHODS: In a multicenter study, lymph node
      biopsy completed by back-up axillary lymph node dissection was undertaken for
      ipsilateral breast tumor recurrence or new ipsilateral primary tumor. Tracer
      uptake was used to identify and isolate the sentinel lymph node during surgery,
      and it was classified after staining with hematoxylin and eosin and monoclonal
      anti-cytokeratin antibodies. Aside from negative predictive value, overall
      accuracy and false-negative rate of repeat sentinel lymph node biopsy were
      assessed. A multicenter, prospective study was conducted performing 30 repeat
      sentinel lymph node biopsy completed by back-up axillary lymph node dissection
      for ipsilateral breast tumor recurrence or new ipsilateral primary tumor in
      patients formerly treated with previous breast conservative surgery and negative
      sentinel lymph node biopsy. Negative predictive value, overall accuracy and false
      negative rate of repeat sentinel lymph node biopsy were assessed. RESULTS:
      Sentinel lymph nodes were mapped in 27 patients out of 30 (90%). Aberrant
      drainage pathways were observed in one patient (3.7%). Tracer uptake was
      sufficient to identify and isolate the sentinel lymph node during surgery in 23
      cases (76.6%); the patients in whom lymphoscintigraphy failed or no sentinel
      lymph nodes could be isolated underwent axillary lymph node dissection. The
      negative predictive value was 95.2%, the accuracy was 95.6% and the false
      negative rate was 33%. CONCLUSIONS: Repeat sentinel lymph node biopsy is feasible
      and accurate, with a high negative predictive value. Patients with ipsilateral
      breast tumor recurrence or new ipsilateral primary tumor after previous breast
      conservative surgery and negative sentinel lymph node biopsy can be treated with
      repeat sentinel lymph node biopsy for the axillary staging and can be spared
      axillary dissection in case of absence of metastases. However, repeat sentinel
      lymph node biopsy may prove technically impracticable in about one quarter of
      cases and thus axillary lymph node dissection remains the only viable option in
      such instance.

PMID- 26207568
TI  - Increased Nuchal Translucency and Early Growth Retardation Related to Confined
      Placental Mosaicism of Trisomy 16 in a Dichorionic Twin.
AB  - Confined placental mosaicism (CPM) of trisomy 16 is related to intrauterine
      growth restriction; however, its association with increased nuchal translucency
      (NT) has not been sufficiently studied. We report the first case involving a
      diagnosis of CPM for trisomy 16 in a dichorionic twin. Increased NT (3.7 mm) and
      1 week of growth retardation at 12 weeks of gestational age were detected in the
      affected fetus compared with the normal fetus. Given that the biochemical
      analytes in maternal serum aneuploidy screening of the abnormal fetus were
      diluted by the presence of the normal fetus, this method was unreliable as a
      screening tool. Therefore, in dichorionic twins, ultrasonographic findings such
      as increased NT and early growth retardation can serve as important indicators
      for the diagnosis of CPM of trisomy 16.

PMID- 26207569
TI  - Investigation into the aerodynamic processes of air treatment using a plate-type
      biofilter.
AB  - The research conducted has involved a laboratory stand of a plate-type air
      treatment biofilter with a capillary system for humidifying packing material
      composed of polymer plates vertically arranged next to each other and producing a
      capillary effect of humidification. The pattern of arranging the plates has
      sufficiently large spaces (6 mm), and therefore the use of the plate-type
      structure decreases the aerodynamic resistance of the device. Slightly pressed
      slabs attached on both sides of the plates are made of heat-treated wood fibre,
      to increase the longevity of which, wood waste has been heat-treated in the steam
      explosion reactor under the pressure of 32 bars and a temperature of 235  degrees
      C. This is the method for changing the molecular structure of wood, which stops
      the decay of wood fibre in a humid environment and thus increases the life span
      of biofilter plates. The research performed has disclosed that, under the
      application of the above introduced structure of the biofilter, the aerodynamic
      resistance of the biofilter reaches 1 / 5 Pa when the rate of the air flow
      passing through the device makes 0.08 m/s. For evaluating the reliability of the
      obtained results, the theoretical model has been applied.

PMID- 26207570
TI  - Effect of a legal prime on clinician's assessment of suicide risk.
AB  - The present study evaluates how liability influences mental health clinicians'
      assessment of suicide risk. In this online vignette-based experiment, clinicians
      (N = 268) were either primed with a legal standard prior to a case vignette or
      presented the case vignette alone. Clinicians then rated the patient's likelihood
      of suicide and need for hospitalization. Results indicated that trainees provided
      significantly lower ratings of suicide risk following presentation of the legal
      standard, but this was not associated with hospitalization endorsement. Results
      have training and legal implications for improving the accuracy of suicide risk
      assessment in both trainees and licensed professionals. 

PMID- 26207571
TI  - Gene Therapy in Nordic Countries.

PMID- 26207572
TI  - Computational Studies of Synthetically Relevant Homogeneous Organometallic
      Catalysis Involving Ni, Pd, Ir, and Rh: An Overview of Commonly Employed DFT
      Methods and Mechanistic Insights.

PMID- 26207573
TI  - ?

PMID- 26207575
TI  - ?

PMID- 26207574
TI  - ?

PMID- 26207576
TI  - ?

PMID- 26207577
TI  - ?

PMID- 26207578
TI  - A zero-liquid-discharge scheme for vanadium extraction process by electrodialysis
      based technology.
AB  - The sharp increase of demand for vanadium makes the treatment of the wastewater
      generated from its extraction process become an urgent problem. In this study, a
      hybrid process coupling the electrodialysis with the cooling crystallization is
      put forward for upgrading the conventional vanadium extraction process to zero
      discharge. Accordingly, the objective of this work lies in evaluating the
      feasibility of the proposed scheme on the basis of a systematic study on the
      influences of membrane types and operating parameters on the electrodialysis
      performance. The results indicate that the relative importance of osmosis and
      electro-osmosis to overall water transport is closely related to the applied
      current density. The increase in the applied current density and the decrease in
      the mole ratio of water and salt flux will contribute to the concentration
      degree. Moreover, it is worth noting that a relatively large concentration ratio
      can result in the remarkable decrease of current efficiency and increase of
      energy consumption. In general, the reclamation scheme can easily achieve the
      recovered water with relatively low salt content and the highly concentrated
      Na2SO4 solution (e.g., 300 g/L) for producing high-purity sodium sulphate
      crystals.

PMID- 26207579
TI  - Dynamics of phosphorus-iron-sulfur at the sediment-water interface influenced by
      algae blooms decomposition.
AB  - This study addresses the previously unknown effects of algae blooms on the
      dynamics of phosphorus (P), iron (Fe) and sulfur (S) across a lacustrine sediment
      water interface (SWI). A mesocosm experiment was conducted in-situ to investigate
      these effects based on two recently-developed diffusive gradients in thin-films
      techniques (DGT). Soluble P, Fe(II), and S(-II) exhibited similar changing trends
      in a water column subject to the algae addition. Peak concentrations appeared on
      day 7 of the 16-day experiment. The lowest Eh occurred at the experiment's midway
      point indicating a strong algae degradation. A maximum increase in DGT-labile S
      appeared on day 8 near the SWI, while the DGT-labile P and Fe exhibited
      persistent increases almost to the end of experiment. Significantly positive
      correlations of labile P were observed switching from between labile Fe and
      labile S in sediments, suggesting a significant change in original Fe-coupled
      dynamics of P under algae decomposition. Apparent fluxes were calculated based on
      DGT profiles where a simultaneous release of P and S occurred from degraded
      algae, resulting in bidirectional diffusion fluxes from sediment to overlying
      water. In contrast, sediment acted as a major source of labile Fe due to added
      depth and apparently positive fluxes. 

PMID- 26207580
TI  - CT of Normal Developmental and Variant Anatomy of the Pediatric Skull:
      Distinguishing Trauma from Normality.
AB  - The use of computed tomography (CT) in clinical practice has been increasing
      rapidly, with the number of CT examinations performed in adults and children
      rising by 10% per year in England. Because the radiology community strives to
      reduce the radiation dose associated with pediatric examinations, external
      factors, including guidelines for pediatric head injury, are raising expectations
      for use of cranial CT in the pediatric population. Thus, radiologists are
      increasingly likely to encounter pediatric head CT examinations in daily
      practice. The variable appearance of cranial sutures at different ages can be
      confusing for inexperienced readers of radiologic images. The evolution of
      multidetector CT with thin-section acquisition increases the clarity of some of
      these sutures, which may be misinterpreted as fractures. Familiarity with the
      normal anatomy of the pediatric skull, how it changes with age, and normal
      variants can assist in translating the increased resolution of multidetector CT
      into more accurate detection of fractures and confident determination of
      normality, thereby reducing prolonged hospitalization of children with normal
      developmental structures that have been misinterpreted as fractures. More
      important, the potential morbidity and mortality related to false-negative
      interpretation of fractures as normal sutures may be avoided. The authors
      describe the normal anatomy of all standard pediatric sutures, common variants,
      and sutural mimics, thereby providing an accurate and safe framework for CT
      evaluation of skull trauma in pediatric patients.

PMID- 26207581
TI  - Body MR Imaging: Artifacts, k-Space, and Solutions.
AB  - Body magnetic resonance (MR) imaging is challenging because of the complex
      interaction of multiple factors, including motion arising from respiration and
      bowel peristalsis, susceptibility effects secondary to bowel gas, and the need to
      cover a large field of view. The combination of these factors makes body MR
      imaging more prone to artifacts, compared with imaging of other anatomic regions.
      Understanding the basic MR physics underlying artifacts is crucial to recognizing
      the trade-offs involved in mitigating artifacts and improving image quality.
      Artifacts can be classified into three main groups: (a) artifacts related to
      magnetic field imperfections, including the static magnetic field, the
      radiofrequency (RF) field, and gradient fields; (b) artifacts related to motion;
      and (c) artifacts arising from methods used to sample the MR signal. Static
      magnetic field homogeneity is essential for many MR techniques, such as fat
      saturation and balanced steady-state free precession. Susceptibility effects
      become more pronounced at higher field strengths and can be ameliorated by using
      spin-echo sequences when possible, increasing the receiver bandwidth, and
      aligning the phase-encoding gradient with the strongest susceptibility gradients,
      among other strategies. Nonuniformities in the RF transmit field, including
      dielectric effects, can be minimized by applying dielectric pads or imaging at
      lower field strength. Motion artifacts can be overcome through respiratory
      synchronization, alternative k-space sampling schemes, and parallel imaging.
      Aliasing and truncation artifacts derive from limitations in digital sampling of
      the MR signal and can be rectified by adjusting the sampling parameters.
      Understanding the causes of artifacts and their possible solutions will enable
      practitioners of body MR imaging to meet the challenges of novel pulse sequence
      design, parallel imaging, and increasing field strength.

PMID- 26207582
TI  - From Shades of Gray to Microbiologic Imaging: A Historical Review of Brain
      Abscess Imaging: RSNA Centennial Article.

PMID- 26207583
TI  - Decision making under explicit risk is impaired in individuals with human
      immunodeficiency virus (HIV).
AB  - INTRODUCTION: Human immunodeficiency virus (HIV) can affect the frontal-striatal
      brain regions, which are known to subserve decision-making functions. Previous
      studies have reported impaired decision making among HIV+ individuals using the
      Iowa Gambling Task, a task that assesses decision making under ambiguity.
      Previous study populations often had significant comorbidities such as past or
      present substance use disorders and/or hepatitis C virus coinfection,
      complicating conclusions about the unique contributions of HIV-infection to
      decision making. Decision making under explicit risk has very rarely been
      examined in HIV+ individuals and was tested here using the Game of Dice Task
      (GDT). METHOD: We examined decision making under explicit risk in the GDT in 20
      HIV+ individuals without substance use disorder or HCV coinfection, including a
      demographically matched healthy control group (n = 20). Groups were characterized
      on a standard neuropsychological test battery. For the HIV+ group, several
      disease-related parameters (viral load, current and nadir CD4 T-cell count) were
      included. Analyses focused on the GDT and spanned between-group (t-tests;
      analysis of covariance, ANCOVA) as well as within-group comparisons
      (Pearson/Spearman correlations). RESULTS: HIV+ individuals were impaired in the
      GDT, compared to healthy controls (p = .02). Their decision-making impairments
      were characterized by less advantageous choices and more random choice
      strategies, especially towards the end of the task. Deficits in the GDT in the
      HIV+ group were related to executive dysfunctions, slowed processing/motor speed,
      and current immune system status (CD4+ T-cell levels, ps < .05). CONCLUSIONS:
      Decision making under explicit risk in the GDT can occur in HIV-infected
      individuals without comorbidities. The correlational patterns may point to
      underlying fronto-subcortical dysfunctions in HIV+ individuals. The GDT provides
      a useful measure to assess risky decision making in this population and should be
      tested in larger studies.

PMID- 26207585
TI  - Current technologies in the extraction, enrichment and analytical detection of
      tocopherols and tocotrienols: A review.
AB  - During the past few years the scientific and medical community has been
      confronted with a continual interest in vitamin E with the interest prompted by
      new discoveries. Tocopherols and tocotrienols, commonly known as vitamin E, are
      extremely invaluable compounds and have various nutritional functionalities and
      benefits to human health. Great deals of research projects have been launched in
      order to develop effective methods for the extraction of vitamin E. By and large,
      three distinct extractive methods are usually employed: supercritical fluid
      extraction (SFE), molecular distillation, and adsorption methods. These methods
      are sensitive to different experimental conditions, such as pressure,
      temperature, and flow rate with noticeable effects on the efficiency of the
      extraction and enrichment of vitamin E. This review has covered the most commonly
      adapted extraction methods and has probed into the extraction yields under
      variable operational parameters.

PMID- 26207586
TI  - Detachment of particles and particle clusters from liquid/liquid interfaces.
AB  - The detachment of microspheres from a liquid/liquid interface triggered by body
      forces is studied experimentally, both for the case of single particles and for
      particle clusters. The values of the critical force required to detach particles
      from the interface are in agreement with the maximum values of the wetting force
      keeping a particles at the interface. In the case of particle clusters, a
      rearrangement of the cluster configuration from a raft to a more compact
      structure is observed when the body force is increased. Clusters detach from the
      liquid/liquid interface at smaller acceleration values than single particles. The
      critical accelerations required to detach particle clusters are consistent with
      models assuming that the wetting force acts at the circumference of a spherical
      or hemispherical densely packed particle cluster. These models predict that the
      critical acceleration for particle clusters scales as n(-2/3), where n is the
      number of particles in a cluster. 

PMID- 26207584
TI  - Vpx mediated degradation of SAMHD1 has only a very limited effect on lentiviral
      transduction rate in ex vivo cultured HSPCs.
AB  - Understanding how to achieve efficient transduction of hematopoietic stem and
      progenitor cells (HSPCs), while preserving their long-term ability to self
      reproduce, is key for applying lentiviral-based gene engineering methods. SAMHD1
      is an HIV-1 restriction factor in myeloid and resting CD4+ T cells that
      interferes with reverse transcription by decreasing the nucleotide pools or by
      its RNase activity. Here we show that SAMHD1 is expressed at high levels in HSPCs
      cultured in a medium enriched with cytokines. Thus, we hypothesized that
      degrading SAMHD1 in HSPCs would result in more efficient lentiviral transduction
      rates. We used viral like particles (VLPs) containing Vpx, shRNA against SAMHD1,
      or provided an excess of dNTPs or dNs to study this question. Regardless of the
      method applied, we saw no increase in the lentiviral transduction rate. The
      result was different when we used viruses (HR-GFP-Vpx+) which carry Vpx and
      encode GFP. These viruses allow assessment of the effects of Vpx specifically in
      the transduced cells. Using HR-GFP-Vpx+ viruses, we observed a modest but
      significant increase in the transduction efficiency. These data suggest that
      SAMHD1 has some limited efficacy in blocking reverse transcription but the major
      barrier for efficient lentiviral transduction occurs before reverse
      transcription.

PMID- 26207587
TI  - An investigation into the nature and potential of in-situ surfactants for low
      energy miniemulsification.
AB  - HYPOTHESIS: It has been reported that surfactants generated in-situ are more
      efficient than their preformed analogues in preparation of miniemulsions for
      application in miniemulsion polymerization but conflicting experimental evidence
      exists over their use. Herein, the potential of preparing miniemulsions using in
      situ generated surfactants is evaluated using KOH/oleic acid as a model system.
      EXPERIMENTS: The kinetics of miniemulsification using either preformed or in-situ
      generated potassium oleate were evaluated by monitoring the evolution of droplet
      size, pH and conductivity during miniemulsification using sonication.
      Subsequently, the kinetics of surfactant adsorption to the monomer/water
      interface were studied using dynamic interfacial tension measurements. Finally,
      the ability of in-situ generated potassium oleate to produce miniemulsions under
      low shear was evaluated under a range of conditions. FINDINGS: No difference in
      the evolution of droplet size, pH or conductivity was observed between the two
      surfactant systems when sonication was applied. Dynamic interfacial tension
      measurements showed that using in-situ generated potassium oleate, interfacial
      tension is significantly lower initially, but at long times the two surfactant
      systems reach similar values. Low shear emulsification by in-situ generated
      potassium oleate resulted in a bimodal droplet distribution. Only at very low oil
      contents with high surfactant concentration is the number of nanometer sized
      droplets large enough to account for a miniemulsion polymerization mechanism.

PMID- 26207588
TI  - Wettability behavior of special microscale ZnO nail-coated mesh films for oil
      water separation.
AB  - The surface free energy and geometrical structure are two important factors to
      govern the surface wettability. However, the design and simple synthesis of
      materials with specific surface free energy and geometrical structure, and their
      elaborate regulations are still a key challenge. Herein, through one-step thermal
      evaporation method, we successfully synthesized aligned arrays of highly
      crystallized ZnO with modulated nail structures on the stainless steel meshes for
      the first time. Owing to the decoration of [0001] oriented nail structures, the
      wire surface of meshes were indeed enclosed by the ZnO (0002) facets, which had
      the lowest surface energy in wurtzite structure. Under no any further
      modifications, just by regulating the nail structure and density as well as the
      mesh pore sizes, we not only obtained ZnO nail-coated mesh with hydrophobic,
      oleophilic (oil penetration), and underwater oleophilic properties, but also
      fabricated one with hydrophilic (water penetration), oleophilic (oil
      penetration), and underwater superoleophobic properties. Furthermore,
      interestingly, the separation of oil and water mixture was realized by utilizing
      two ZnO-nail coated meshes with different wettability. The underlying mechanism
      was investigated and discussed in the work. Therefore, our study provides
      interesting insight into the design of novel functional films with desired
      surface wettability for the separation of oil-water mixture. 

PMID- 26207589
TI  - Vaccination of koalas with a prototype chlamydial vaccine is safe, does not
      increase the incidence of lymphoma-related disease and maybe associated with
      increased lifespan in captive koalas.
AB  - OBJECTIVES: To assess the impact of Chlamydia vaccination on survival of captive
      koalas, and to compare the incidence of lymphomas and neoplasias between
      vaccinated and unvaccinated koalas. METHODS: Survival analysis using Cox and
      Weibull regressions on 54 vaccinated and 52 matched unvaccinated koalas, and chi
      square contingency table for incidence of lymphomas/neoplasias. RESULTS:
      Vaccination was found to have a significant positive effect on koala lifespan
      (P=0.03), with vaccinated koalas having a median lifespan of 12.25 years compared
      to 8.8 years for unvaccinated ones. The effect of sex on lifespan was not
      significant (P=0.31). The risk ratio of unvaccinated over vaccinated koalas was
      2.2 with both Cox and Weibull regressions. There was no association between the
      incidence of lymphoma/neoplasias and vaccination status (P=0.33). CONCLUSIONS:
      Koalas vaccinated with a prototype Chlamydia vaccine may live longer than
      unvaccinated ones. There was no known Chlamydia infection among koalas, so our
      interpretation is that vaccination may have boosted the innate and adaptive
      immune systems to protect against a wide spectrum of bacteria, fungi and
      parasites. Vaccinated koalas did not show negative physiological effects of the
      vaccine, for example, the frequency of deaths due to lymphomas/neoplasias was the
      same in both vaccinated and unvaccinated animals.

PMID- 26207591
TI  - OmpW is a potential target for eliciting protective immunity against
      Acinetobacter baumannii infections.
AB  - Acinetobacter baumannii (A. baumannii) is an important conditioned pathogen that
      causes nosocomial and community-associated infections. In this study, we sought
      to investigate whether outer membrane protein W (OmpW) is a potential target for
      eliciting protective immunity against A. baumannii infections. Mice immunized
      with the fusion protein thioredoxin-OmpW generated strong OmpW-specific IgG
      responses. In a sepsis model, both active and passive immunizations against OmpW
      effectively protected mice from A. baumannii infections. This protection was
      demonstrated by a significantly improved survival rate, reduced bacterial burdens
      within organs, and the suppressed accumulation of inflammatory cytokines and
      chemokines in sera. Opsonophagocytic assays with murine macrophage RAW264.7 cells
      indicated that the bactericidal effects of the antisera derived from the
      immunized mice are mediated synergistically by specific antibodies and complement
      components. The antisera presented significant opsonophagocytic activities
      against homologous strains and clonally distinct clinical isolates in vitro.
      Protein data analysis showed that the sequence of OmpW, which has a molecule
      length of 183 amino acids, is more than 91% conserved in reported A. baumannii
      strains. In conclusion, we identified OmpW as a highly immunogenic and conserved
      protein as a valuable antigen candidate for the development of an effective
      vaccine or the preparation of antisera to control A. baumannii infections. 

PMID- 26207590
TI  - Recombinant H7 hemagglutinin forms subviral particles that protect mice and
      ferrets from challenge with H7N9 influenza virus.
AB  - A novel avian-origin influenza A H7N9 virus emerged in China in 2013 and
      continues to cause sporadic human infections with mortality rates approaching
      35%. Currently there are no approved human vaccines for H7N9 virus. Recombinant
      approaches including hemagglutinin (HA) and virus-like particles (VLPs) have
      resulted in experimental vaccines with advantageous safety and manufacturing
      characteristics. While high immunogenicity of VLP vaccines has been attributed to
      the native conformation of HA arranged in the regular repeated patterns within
      virus-like structures, there is limited data regarding molecular organization of
      HA within recombinant HA vaccine preparations. In this study, the full-length
      recombinant H7 protein (rH7) of A/Anhui/1/2013 (H7N9) virus was expressed in Sf9
      cells. We showed that purified full-length rH7 retained functional ability to
      agglutinate red blood cells and formed oligomeric pleomorphic subviral particles
      (SVPs) of ~20nm in diameter composed of approximately 10 HA0 molecules. No
      significant quantities of free monomeric HA0 were observed in rH7 preparation by
      size exclusion chromatography. Immunogenicity and protective efficacy of rH7 SVPs
      was confirmed in the mouse and ferret challenge models suggesting that SVPs can
      be used for vaccination against H7N9 virus. 

PMID- 26207592
TI  - A putative amino acid ABC transporter substrate-binding protein, NMB1612, from
      Neisseria meningitidis, induces murine bactericidal antibodies against
      meningococci expressing heterologous NMB1612 proteins.
AB  - The nmb1612 (NEIS1533) gene encoding the ~27-kDa putative amino acid ATP-binding
      cassette (ABC) transporter, periplasmic substrate-binding protein from Neisseria
      meningitidis serogroup B (MenB) strain MC58 was cloned and expressed in
      Escherichia coli, and the purified recombinant (r)NMB1612 was used for animal
      immunization studies. Immunization of mice with rNMB1612 adsorbed to Al(OH)3 and
      in liposomes with and without MPLA, induced antiserum with bactericidal activity
      in an assay using baby rabbit complement, against the homologous strain MC58
      (encoding protein representative of Allele 62) and killed heterologous strains
      encoding proteins of three other alleles (representative of Alleles 1, 64 and
      68), with similar SBA titres. However, strain MC58 was not killed (titre <4) in a
      human serum bactericidal assay (hSBA) using anti-rNMB1612 sera, although another
      strain (MC168) expressing the same protein was killed (median titres of 16-64 in
      the hSBA). Analysis of the NMB1612 amino acid sequences from 4351 meningococcal
      strains in the pubmlst.org/Neisseria database and a collection of 13 isolates
      from colonized individuals and from patients, showed that antibodies raised
      against rNMB1612 could potentially kill at least 72% of the MenB strains in the
      complete sequence database. For MenB disease occurring specifically in the UK
      from 2013 to 2015, >91% of the isolates causing disease in this recent period
      expressed NMB1612 protein encoded by Allele 1 and could be potentially killed by
      sera raised to the recombinant antigen in the current study. The NMB1612 protein
      was surface-accessible and expressed by different meningococcal strains. In
      summary, the properties of (i) NMB1612 protein conservation and expression, (ii)
      limited amino acid sequence variation between proteins encoded by different
      alleles, and (iii) the ability of a recombinant protein to induce cross-strain
      bactericidal antibodies, would all suggest a promising antigen for consideration
      for inclusion in new meningococcal vaccines.

PMID- 26207593
TI  - Tick borne encephalitis (TBE)-vaccination coverage and analysis of variables
      associated with vaccination, Sweden.
AB  - To estimate the tick borne encephalitis (TBE)-vaccination coverage in the greater
      Stockholm region, we sent a questionnaire to a randomized sample of 8000
      individuals in 2013. Fifty-three percent of all respondents (n=4307) reported
      being vaccinated against TBE at least once. Reasons for not vaccinating included:
      no perceived risk (28.6%), too expensive (25.6%), did not have the time or
      opportunity (23%) and worried about vaccine side-effects (20.5%). Multiple
      logistic regression revealed that the probability of being vaccinated was higher
      among those who reported >=2 weeks outdoor exposure in a known high risk area (OR
      4.13 95% CI 3.54-4.81) and in individuals >=60 years of age compared to all other
      age groups (OR 0.67 95% CI 0.55-0.81). A high net household income was associated
      with a higher probability of being vaccinated (OR 2.10 95% CI 1.6-2.73). Being
      born outside Europe was negatively correlated (OR 0.57 95% CI 0.39-0.83). Based
      on our findings the estimated TBE-incidence in the unvaccinated regional
      population was 8.5-12/100,000 which is comparable with high endemic areas as the
      Baltic region and Central Europe. We suggest targeted vaccination and
      reimbursement strategies in high-endemic areas of Sweden. Our results indicate a
      need for improved public information about TBE. 

PMID- 26207594
TI  - Differences in motor performance between children and adolescents in Mozambique
      and Portugal: impact of allometric scaling.
AB  - BACKGROUND: Children from developed and developing countries have different
      anthropometric characteristics which may affect their motor performance (MP).
      AIM: To use the allometric approach to model the relationship between body size
      and MP in youth from two countries differing in socio-economic status-Portugal
      and Mozambique. SUBJECTS AND METHODS: A total of 2946 subjects, 1280 Mozambicans
      (688 girls) and 1666 Portuguese (826 girls), aged 10-15 years were sampled.
      Height and weight were measured and the reciprocal ponderal index (RPI) was
      computed. MP included handgrip strength, 1-mile run/walk, curl-ups and standing
      long jump tests. A multiplicative allometric model was adopted to adjust for body
      size differences across countries. RESULTS: Differences in MP between Mozambican
      and Portuguese children exist, invariably favouring the latter. The allometric
      models used to adjust MP for differences in body size identified the optimal body
      shape to be either the RPI or even more linear, i.e. approximately
      (height/mass(0.25)). Having adjusted the MP variables for differences in body
      size, the differences between Mozambican and Portuguese children were invariably
      reduced and, in the case of grip strength, reversed. CONCLUSION: These results
      reinforce the notion that significant differences exist in MP across countries,
      even after adjusting for differences in body size.

PMID- 26207595
TI  - Geographic distribution of ATP7B mutations in Wilson disease.
AB  - CONTEXT: Geographic distribution of ATP7B mutations in different populations.
      OBJECTIVE: To summarise common mutations in the ATP7B gene and graphically
      illustrate their prevalence in different populations. METHODS: A literature
      search was done using PubMed and the Wilson Disease Mutation Database
      (http://www.wilsondisease.med.ualberta.ca/database). RESULTS: p.His1069Gln is the
      most prevalent mutation seen in Europe. In the Mediterranean countries, the array
      of prevalent mutations is different from the rest of Europe. In Far East Asian
      countries, the mutation p.Arg778Leu is the most common. In India, no single
      mutation seems to be dominant, owing to the vast ethnic diversity of the country.
      The p.Cys271* mutation is dominant in the east, west and south, but not reported
      in the north. In the Middle East, data from Saudi Arabia shows the p.Gln1399Arg
      mutation as the most prevalent. In the US, the p.His1069Gln is dominant, whereas
      in Brazil the mutation c.3402delC dominates. CONCLUSION: Clinical features in WD
      patients can be misleading and often absent. Genetic testing is used to confirm
      the diagnosis. However, owing to the large gene size and vast diversity in the
      mutations, genetic testing can be time-consuming and tedious. This study reviews
      ATP7B mutations seen in different populations and can help develop time-saving
      methods and expediate the process of genetic analysis of WD.

PMID- 26207596
TI  - Baseline frequency of chromosomal aberrations and sister chromatid exchanges in
      peripheral blood lymphocytes of healthy individuals living in Turin (North
      Western Italy): assessment of the effects of age, sex and GSTs gene polymorphisms
      on the levels of genomic damage.
AB  - BACKGROUND: The increased exposure to environmental pollutants has led to the
      awareness of the necessity for constant monitoring of human populations,
      especially those living in urban areas. AIM: This study evaluated the background
      levels of genomic damage in a sample of healthy subjects living in the urban area
      of Turin (Italy). The association between DNA damage with age, sex and GSTs
      polymorphisms was assessed. SUBJECTS AND METHODS: One hundred and one individuals
      were randomly sampled. Sister Chromatid Exchanges (SCEs) and Chromosomal
      Aberrations (CAs) assays, as well as genotyping of GSTT1 and GSTM1 genes, were
      performed. RESULTS: Mean values of SCEs and CAs were 5.137 +/- 0.166 and 0.018 +/
      0.002, respectively. Results showed age and gender associated with higher
      frequencies of these two cytogenetic markers. The eldest subjects (51-65 years)
      showed significantly higher levels of genomic damage than younger individuals.
      GSTs polymorphisms did not appear to significantly influence the frequencies of
      either markers. CONCLUSION: The CAs background frequency observed in this study
      is one of the highest reported among European populations. Turin is one of the
      most polluted cities in Europe in terms of air fine PM10 and ozone and the
      clastogenic potential of these pollutants may explain the high frequencies of
      chromosomal rearrangements reported here.

PMID- 26207597
TI  - Explorative genetic association study of GSTT2B copy number variant in complex
      disease risks.
AB  - BACKGROUND: Glutathione S-transferases (GSTs) are the main phase II enzymes
      involved in cellular detoxification. Through phase I and phase II detoxification
      reactions, the cell is able to detoxify endogenous and exogenous toxic compounds.
      AIMS: This study focused attention on the GSTT2B copy number variant (CNV) in
      order to explore its involvement in the genetic pre-disposition to asthma,
      Alzheimer's disease (AD), allergic rhinitis (AR), essential hypertension (EH),
      hypothyroidism and recurrent miscarriage (RM). METHODS: The study population
      consists of 1225 individuals divided into six case-control groups. The genotyping
      of the GSTT2B CNV was performed by using a duplex-PCR. Odds Ratios (ORs) were
      calculated, adjusting for the confounding variables, to estimate the association
      between GSTT2B CNV and the disease status. RESULTS: The chi(2)-test and ORs did
      not show any association between this genetic marker and pathological phenotypes.
      CONCLUSION: The data highlights that GSTT2B CNV is not associated with the
      investigated complex diseases in Italian patients. However, further
      investigations are necessary to replicate these findings in larger sample sizes
      and to explore other health-related phenotypes.

PMID- 26207598
TI  - The association of cardiorespiratory fitness to health independent of adiposity
      depends upon its expression.
AB  - BACKGROUND: The strong relation between cardiorespiratory fitness (CRF) and
      adiposity renders their independent associations to metabolic risk factors
      difficult to ascertain. AIM: To determine the associations of CRF and CRF
      relative to fat-free mass (CRFFFM) to total cholesterol, high-density
      lipoprotein, low-density lipoprotein, triglycerides, glucose, insulin and
      homeostasis model assessment (HOMA) and distinguish these relations from the
      association to adiposity. SUBJECTS AND METHODS: Anthropometrics, body fat
      percentage (%Fat) and fat-free mass (from dual energy X-ray absorptiometry) were
      measured in 127 (66 females) 17 and 23 year-olds. CRF from a maximal workload on
      a graded bicycle test and fasting blood samples were obtained. RESULTS: CRF was
      significantly related to total cholesterol, triglycerides, insulin and HOMA (r = 
      0.24 to -0.49, p < 0.03), as were all adiposity measures (r = 0.21-0.53, p <
      0.05). Correcting CRF for %Fat rendered the relation to metabolic risk factors
      non-significant (p = 0.09-0.21); however, CRFFFM was significantly related to the
      metabolic risk factors (r = -0.25 to -0.32, p < 0.02). CONCLUSIONS: CRFFFM, where
      adiposity has been removed, is associated with metabolic risk factors, whereas
      CRF, which is related to adiposity, is not after adjustment for fatness.
      Previously, independent effects of CRF on health may have been underestimated by
      using an expression of CRF strongly related to the adiposity measures.

PMID- 26207599
TI  - Restoration of ankle movements with the ActiGait implantable drop foot
      stimulator: a safe and reliable treatment option for permanent central leg palsy.
AB  - OBJECT The ActiGait drop foot stimulator is a promising technique for restoration
      of lost ankle function by an implantable hybrid stimulation system. It allows
      ankle dorsiflexion by active peroneal nerve stimulation during the swing phase of
      gait. In this paper the authors report the outcome of the first prospective study
      on a large number of patients with stroke-related drop foot. METHODS Twenty-seven
      patients who experienced a stroke and with persisting spastic leg paresis
      received an implantable ActiGait drop foot stimulator for restoration of ankle
      movement after successful surface test stimulation. After 3 to 5 weeks, the
      stimulator was activated, and gait speed, gait endurance, and activation time of
      the system were evaluated and compared with preoperative gait tests. In addition,
      patient satisfaction was assessed using a questionnaire. RESULTS Postoperative
      gait speed significantly improved from 33.9 seconds per 20 meters to 17.9 seconds
      per 20 meters (p < 0.0001), gait endurance from 196 meters in 6 minutes to 401
      meters in 6 minutes (p < 0.0001), and activation time from 20.5 seconds to 10.6
      seconds on average (p < 0.0001). In 2 patients with nerve injury, surgical
      repositioning of the electrode cuff became necessary. One patient showed a
      delayed wound healing, and in another patient the system had to be removed
      because of a wound infection. Marked improvement in mobility, social
      participation, and quality of life was confirmed by 89% to 96% of patients.
      CONCLUSIONS The ActiGait implantable drop foot stimulator improves gait speed,
      endurance, and quality of life in patients with stroke-related drop foot.
      Regarding gait speed, the ActiGait system appears to be advantageous compared
      with foot orthosis or surface stimulation devices. Randomized trials with more
      patients and longer observation periods are needed to prove the long-term benefit
      of this device. 

PMID- 26207600
TI  - Magnetic resonance susceptibility weighted imaging in neurosurgery: current
      applications and future perspectives.
AB  - Susceptibility weighted imaging (SWI) is a relatively new imaging technique. Its
      high sensitivity to hemorrhagic components and ability to depict microvasculature
      by means of susceptibility effects within the veins allow for the accurate
      detection, grading, and monitoring of brain tumors. This imaging modality can
      also detect changes in blood flow to monitor stroke recovery and reveal specific
      subtypes of vascular malformations. In addition, small punctate lesions can be
      demonstrated with SWI, suggesting diffuse axonal injury, and the location of
      these lesions can help predict neurological outcome in patients. This imaging
      technique is also beneficial for applications in functional neurosurgery given
      its ability to clearly depict and differentiate deep midbrain nuclei and close
      submillimeter veins, both of which are necessary for presurgical planning of deep
      brain stimulation. By exploiting the magnetic susceptibilities of substances
      within the body, such as deoxyhemoglobin, calcium, and iron, SWI can clearly
      visualize the vasculature and hemorrhagic components even without the use of
      contrast agents. The high sensitivity of SWI relative to other imaging techniques
      in showing tumor vasculature and microhemorrhages suggests that it is an
      effective imaging modality that provides additional information not shown using
      conventional MRI. Despite SWI's clinical advantages, its implementation in MRI
      protocols is still far from consistent in clinical usage. To develop a deeper
      appreciation for SWI, the authors here review the clinical applications in 4
      major fields of neurosurgery: neurooncology, vascular neurosurgery,
      neurotraumatology, and functional neurosurgery. Finally, they address the
      limitations of and future perspectives on SWI in neurosurgery.

PMID- 26207601
TI  - Robotic intercostal nerve harvest: a feasibility study in a pig model.
AB  - The aim of this study was to report the feasibility of robotic intercostal nerve
      harvest in a pig model. A surgical robot, the da Vinci Model S system, was
      installed after the creation of 3 ports in the pig's left chest. The posterior
      edges of the fourth, fifth, and sixth intercostal nerves were isolated at the
      level of the anterior axillary line. The anterior edges of the nerves were
      transected at the rib cartilage zone. Three intercostal nerve harvesting
      procedures, requiring an average of 33 minutes, were successfully performed in 3
      pigs without major complications. The advantages of robotic microsurgery for
      intercostal nerve harvest include elimination of physiological tremor, free
      movement of joint-equipped robotic arms, and amplification of the surgeon's hand
      motion by as much as 5 times. Robot-assisted neurolysis may be clinically useful
      for intercostal nerve harvest for brachial plexus reconstruction. 

PMID- 26207602
TI  - Temporal lobe epilepsy in patients with nonlesional MRI and normal memory: an
      SEEG study.
AB  - OBJECT: Temporal lobe epilepsy (TLE) in the absence of MRI abnormalities and
      memory deficits is often presumed to have an extramesial or even extratemporal
      source. In this paper the authors report the results of a comprehensive
      stereoelectroencephalography (SEEG) analysis in patients with TLE with normal MRI
      images and memory scores. METHODS: Eighteen patients with medically refractory
      epilepsy who also had unremarkable MR images and normal verbal and visual memory
      scores on neuropsychological testing were included in the study. All patients had
      seizure semiology and video electroencephalography (EEG) findings suggestive of
      TLE. A standardized SEEG investigation was performed for each patient with
      electrodes implanted into the mesial and lateral temporal lobe, temporal tip,
      posterior temporal neocortex, orbitomesiobasal frontal lobe, posterior cingulate
      gyrus, and insula. This information was used to plan subsequent surgical
      management. RESULTS: Interictal SEEG abnormalities were observed in the mesial
      temporal structures in 17 patients (94%) and in the temporal tip in 6 (33%).
      Seizure onset was exclusively from mesial structures in 13 (72%), exclusively
      from lateral temporal cortex and/or temporal tip structures in 2 (11%), and
      independently from mesial and neocortical foci in 3 (17%). No seizure activity
      was observed arising from any extratemporal location. All patients underwent
      surgical intervention targeting the temporal lobe and tailored to the SEEG
      findings, and all experienced significant improvement in seizure frequency with a
      postoperative follow-up observation period of at least 1 year. CONCLUSIONS: This
      study demonstrates 3 important findings: 1) normal memory does not preclude
      mesial temporal seizure onset; 2) onset of seizures exclusively from mesial
      temporal structures without early neocortical involvement is common, even in the
      absence of memory deficits; and 3) extratemporal seizure onset is rare when video
      EEG and semiology are consistent with focal TLE.

PMID- 26207603
TI  - Editorial: Misrepresentation among neurosurgery residency applicants.

PMID- 26207604
TI  - Predicting success of endoscopic third ventriculostomy: validation of the ETV
      Success Score in a mixed population of adult and pediatric patients.
AB  - OBJECT: Endoscopic third ventriculostomy (ETV) has become the first line of
      treatment in obstructive hydrocephalus. The Toronto group (Kulkarni et al.)
      developed the ETV Success Score (ETVSS) to predict the clinical response
      following ETV based on age, previous shunt, and cause of hydrocephalus in a
      pediatric population. However, the use of the ETVSS has not been validated for a
      population comprising adults. The objective of this study was to validate the
      ETVSS in a "closed-skull" population, including patients 2 years of age and
      older. METHODS: In this retrospective observational study, medical charts of all
      consecutive cases of ETV performed in two university hospitals were reviewed. The
      primary outcome, the success of ETV, was defined as the absence of reoperation or
      death attributable to hydrocephalus at 6 months. The ETVSS was calculated for all
      patients. Discriminative properties along with calibration of the ETVSS were
      established for the study population. The secondary outcome is the reoperation
      free survival. RESULTS: This study included 168 primary ETVs. The mean age was 40
      years (range 3-85 years). ETV was successful at 6 months in 126 patients (75%)
      compared with a mean ETVSS of 82.4%. The area under the receiver operating
      characteristic curve was 0.61, revealing insufficient discrimination from the
      ETVSS in this population. In contrast, calibration of the ETVSS was excellent
      (calibration slope = 1.01), although the expected low numbers were obtained for
      scores < 70. Decision curve analyses demonstrate that ETVSS is marginally
      beneficial in clinical decision-making, a reduction of 4 and 2 avoidable ETVs per
      100 cases if the threshold used on the ETVSS is set at 70 and 60, respectively.
      However, the use of the ETVSS showed inferior net benefit when compared with the
      strategy of not recommending ETV at all as a surgical option for thresholds set
      at 80 and 90. In this cohort, neither age nor previous shunt were significantly
      associated with unsuccessful ETV. However, better outcomes were achieved in
      patients with aqueductal stenosis, tectal compressions, and other tumor
      associated hydrocephalus than in cases secondary to myelomeningocele, infection,
      or hemorrhage (p = 0.03). CONCLUSIONS: The ETVSS did not show adequate
      discrimination but demonstrated excellent calibration in this population of
      patients 2 years and older. According to decision-curve analyses, the ETVSS is
      marginally useful in clinical scenarios in which 60% or 70% success rates are the
      thresholds for preferring ETV to CSF shunt. Previous history of CSF shunt and age
      were not associated with worse outcomes, whereas posthemorrhagic and
      postinfectious causes of the hydrocephalus were significantly associated with
      reduced success rates following ETV.

PMID- 26207605
TI  - Publication misrepresentation among neurosurgery residency applicants: an
      increasing problem.
AB  - OBJECT Misrepresentation of scholarly achievements is a recognized phenomenon,
      well documented in numerous fields, yet the accuracy of reporting remains
      dependent on the honor principle. Therefore, honest self-reporting is of
      paramount importance to maintain scientific integrity in neurosurgery. The
      authors had observed a trend toward increasing numbers of publications among
      applicants for neurosurgery residency at Vanderbilt University and undertook this
      study to determine whether this change was a result of increased academic
      productivity, inflated reporting, or both. They also aimed to identify
      application variables associated with inaccurate citations. METHODS The authors
      retrospectively reviewed the residency applications submitted to their
      neurosurgery department in 2006 (n = 148) and 2012 (n = 194). The applications
      from 2006 were made via SF Match and those from 2012 were made using the
      Electronic Residency Application Service. Publications reported as "accepted" or
      "in press" were verified via online search of Google Scholar, PubMed, journal
      websites, and direct journal contact. Works were considered misrepresented if
      they did not exist, incorrectly listed the applicant as first author, or were
      incorrectly listed as peer reviewed or published in a printed journal rather than
      an online only or non-peer-reviewed publication. Demographic data were collected,
      including applicant sex, medical school ranking and country, advanced degrees,
      Alpha Omega Alpha membership, and USMLE Step 1 score. Zero-inflated negative
      binomial regression was used to identify predictors of misrepresentation. RESULTS
      Using univariate analysis, between 2006 and 2012 the percentage of applicants
      reporting published works increased significantly (47% vs 97%, p < 0.001).
      However, the percentage of applicants with misrepresentations (33% vs 45%) also
      increased. In 2012, applicants with a greater total of reported works (p < 0.001)
      and applicants from unranked US medical schools (those not ranked by US News &
      World Report) were more likely to have erroneous citations (p = 0.038).
      CONCLUSIONS The incidence of legitimate and misrepresented scholarly works
      reported by applicants to the authors' neurosurgery residency program increased
      during the past 6 years. Misrepresentation is more common in applicants from
      unranked US medical schools and those with a greater number of reported works on
      their application. This trend is concerning in a profession where trustworthiness
      is vital. To preserve integrity in the field, programs should consider verifying
      citations prior to submitting their rank lists. 

PMID- 26207606
TI  - The safety of vasopressor-induced hypertension in subarachnoid hemorrhage
      patients with coexisting unruptured, unprotected intracranial aneurysms.
AB  - OBJECT: Vasopressor-induced hypertension (VIH) is an established treatment for
      patients with aneurysmal subarachnoid hemorrhage (SAH) who develop vasospasm and
      delayed cerebral ischemia (DCI). However, the safety of VIH in patients with
      coincident, unruptured, unprotected intracranial aneurysms is uncertain. METHODS:
      This retrospective multiinstitutional study identified 1) patients with
      aneurysmal SAH and 1 or more unruptured, unprotected aneurysms who required VIH
      therapy (VIH group), and 2) patients with aneurysmal SAH and 1 or more
      unruptured, unprotected aneurysms who did not require VIH therapy (non-VIH
      group). All patients had previously undergone surgical or endovascular treatment
      for the presumed ruptured aneurysm. Comparisons between the VIH and non-VIH
      patients were made in terms of the patient characteristics, clinical and
      radiographic severity of SAH, total number of aneurysms, number of
      ruptured/unruptured aneurysms, aneurysm location/size, number of unruptured and
      unprotected aneurysms during VIH, severity of vasospasm, degree of hypervolemia,
      and degree and duration of VIH therapy. RESULTS: For the VIH group (n = 176), 484
      aneurysms were diagnosed, 231 aneurysms were treated, and 253 unruptured
      aneurysms were left unprotected during 1293 total days of VIH therapy (5.12 total
      years of VIH therapy for unruptured, unprotected aneurysms). For the non-VIH
      group (n = 73), 207 aneurysms were diagnosed, 93 aneurysms were treated, and 114
      unruptured aneurysms were left unprotected. For the VIH and non-VIH groups, the
      mean sizes of the ruptured (7.2 +/- 0.3 vs 7.8 +/- 0.6 mm, respectively; p =
      0.27) and unruptured (3.4 +/- 0.2 vs 3.2 +/- 0.2 mm, respectively; p = 0.40)
      aneurysms did not differ. The authors observed 1 new SAH from a previously
      unruptured, unprotected aneurysm in each group (1 of 176 vs 1 of 73 patients; p =
      0.50). Baseline patient characteristics and comorbidities were similar between
      groups. While the degree of hypervolemia was similar between the VIH and non-VIH
      patients (fluid balance over the first 10 days of therapy: 3146.2 +/- 296.4 vs
      2910.5 +/- 450.7 ml, respectively; p = 0.67), VIH resulted in a significant
      increase in mean arterial pressure (mean increase over the first 10 days of
      therapy relative to baseline: 125.1% +/- 1.0% vs 98.2% +/- 1.2%, respectively; p
      < 0.01) and systolic blood pressure (125.6% +/- 1.1% vs. 104.1% +/- 5.2%,
      respectively; p < 0.01). CONCLUSIONS: For small, unruptured, unprotected
      intracranial aneurysms in SAH patients, the frequency of aneurysm rupture during
      VIH therapy is rare. The authors do not recommend withholding VIH therapy from
      these patients.

PMID- 26207607
TI  - Platelet activating factor receptor: gateway for bacterial chronic airway
      infection in chronic obstructive pulmonary disease and potential therapeutic
      target.
AB  - The authors established that cigarette smoke increases airway epithelial platelet
      activating factor receptor (PAFr) expression and that PAFr is markedly up
      regulated in the lungs of chronic obstructive pulmonary disease (COPD) patients.
      Crucially, PAFr is used by the two key bacterial species involved in chronic
      infection and acute exacerbations in COPD, that is, Streptococcus pneumoniae and
      Haemophilus influenzae, as a receptor for lung epithelial colonization. The
      cognate adhesin of PAFr, phosphorylcholine (ChoP), in the cell wall of these
      bacterial species may be a key effector that underpins host colonization. In this
      review, the authors evaluate the respective roles of PAFr and ChoP in the natural
      history of COPD and discuss the potential of the airway epithelial PAFr-bacterial
      ChoP interaction as a selective anti-infective target in COPD therapeutics. 

PMID- 26207608
TI  - Right ventricular tombstoning as a Brugada phenocopy.

PMID- 26207609
TI  - Influences of Transportation on Health Decision-Making and Self-Management
      Behaviors among Older Adults with Chronic Conditions.
AB  - Although transportation has been established as a facilitator/barrier to health
      self-management, little is known about how the context of transportation shapes
      health self-management behaviors and decision-making among older adults with
      chronic conditions. This study interviewed 37 older adults with chronic
      conditions in Florida to examine their perspectives about how transportation
      influences their chronic care self-management. The data were systematically
      analyzed for themes. The thematic findings revealed how transportation
      intersected with participants' everyday experiences with chronic health self
      management, how they evaluated transportation as part of the process of making
      decisions about health, and how creative problem-solving about transportation
      became an additional health self-management activity for addressing their complex
      needs. These findings suggest that the context of transportation goes beyond a
      basic facilitator/barrier for health and enhance our understanding about how
      transportation services and policies may be changed to better address the needs
      of older adults with chronic conditions.

PMID- 26207611
TI  - Electrostatic and Allosteric Cooperativity in Ion-Pair Binding: A Quantitative
      and Coupled Experiment-Theory Study with Aryl-Triazole-Ether Macrocycles.
AB  - Cooperative binding of ion pairs to receptors is crucial for the manipulation of
      salts, but a comprehensive understanding of cooperativity has been elusive. To
      this end, we combine experiment and theory to quantify ion-pair binding and to
      separate allostery from electrostatics to understand their relative
      contributions. We designed aryl-triazole-ether macrocycles (MC) to be
      semiflexible, which allows ion pairs (NaX; X = anion) to make contact, and to be
      monocyclic to simplify analyses. A multiequilibrium model allows us to quantify,
      for the first time, the experimental cooperativity, alpha, for the equilibrium
      MC.Na(+) + MC.X(-) ? MC.NaX + MC, which is associated with contact ion-pair
      binding of NaI (alpha = 1300, DeltaGalpha = -18 kJ mol(-1)) and NaClO4 (alpha =
      400, DeltaGalpha = -15 kJ mol(-1)) in 4:1 dichloromethane-acetonitrile. We used
      accurate energies from density functional theory to deconvolute how the
      electrostatic effects and the allosteric changes in receptor geometry
      individually contribute to cooperativity. Computations, using a continuum
      solvation model (dichloromethane), show that allostery contributes ~30% to
      overall positive cooperativity. The calculated trend of electrostatic
      cooperativity using pairs of spherical ions (NaCl > NaBr > NaI) correlates to
      experimental observations (NaI > NaClO4). We show that intrinsic ionic size,
      which dictates charge separation distance in contact ion pairs, controls
      electrostatic cooperativity. This finding supports the design principle that
      semiflexible receptors can facilitate optimal electrostatic cooperativity. While
      Coulomb's law predicts the size-dependent trend, it overestimates electrostatic
      cooperativity; we suggest that binding of the individual anion and cation to
      their respective binding sites dilutes their effective charge. This comprehensive
      understanding is critical for rational designs of ion-pair receptors for the
      manipulation of salts. 

PMID- 26207610
TI  - Carboplatin Hypersensitivity Reactions in Pediatric Low Grade Glioma Are Protocol
      Specific and Desensitization Shows Poor Efficacy.
AB  - BACKGROUND: The use of carboplatin for the treatment of pediatric low grade
      gliomas (PLGG) is often limited by the development of carboplatin
      hypersensitivity. Reported rates of carboplatin hypersensitivity reactions vary
      between 6% and 32% in these patients. Here we report the frequency of carboplatin
      hypersensitivity reactions depending on the treatment regimen used, and outcomes
      of carboplatin desensitization. METHODS: The records of all patients in a single
      institution who were treated with carboplatin for PLGG were accessed and all
      patients receiving more than one dose of carboplatin are reported. RESULTS:
      Thirty four patients with PLGG were treated with carboplatin according to one of
      the two different regimens. Carboplatin hypersensitivity was documented in 47% of
      patients, but the frequency differed by treatment protocol. Those patients
      treated with 4-weekly single agent carboplatin had carboplatin allergy in 8% of
      cases whereas 68% of those treated with combined carboplatin and vincristine
      (every three weeks, according to the SIOP 2004 low grade glioma protocol) had
      carboplatin reactions (OR 23.6, P < 0.01). Desensitization was only successful in
      two out of 10 patients in whom it was attempted. CONCLUSIONS: Hypersensitivity
      reactions to carboplatin are more common in this cohort than previously reported
      and rates are protocol-dependent. Desensitization showed limited effectiveness in
      this cohort.

PMID- 26207612
TI  - Inhibition of Mitochondrial Complex-1 Prevents the Downregulation of NKCC2 and
      ENaCalpha in Obstructive Kidney Disease.
AB  - Ureteral obstruction with subsequent hydronephrosis is a common clinical
      complication. Downregulation of renal sodium transporters in obstructed kidneys
      could contribute to impaired urinary concentrating capability and salt waste
      following the release of a ureteral obstruction. The current study was undertaken
      to investigate the role of mitochondrial complex-1 inhibition in modulating
      sodium transporters in obstructive kidney disease. Following unilateral ureteral
      obstruction (UUO) for 7 days, a global reduction of sodium transporters,
      including NHE3, alpha-Na-K-ATPase, NCC, NKCC2, p-NKCC2, ENaCalpha, and ENaCgamma,
      was observed, as determined via qRT-PCR and/or Western blotting. Interestingly,
      inhibition of mitochondrial complex-1 by rotenone markedly reversed the
      downregulation of NKCC2, p-NKCC2, and ENaCalpha. In contrast, other sodium
      transporters were not affected by rotenone. To study the potential mechanisms
      involved in mediating the effects of rotenone on sodium transporters, we examined
      a number of known sodium modulators, including PGE2, ET1, Ang II, natriuretic
      peptides (ANP, BNP, and CNP), and nitric oxide synthases (iNOS, nNOS, and eNOS).
      Importantly, among these modulators, only BNP and iNOS were significantly reduced
      by rotenone treatment. Collectively, these findings demonstrated a substantial
      role of mitochondrial dysfunction in mediating the downregulation of NKCC2 and
      ENaCalpha in obstructive kidney disease, possibly via iNOS-derived nitric oxide
      and BNP. 

PMID- 26207613
TI  - Two complementary approaches for intracellular delivery of exogenous enzymes.
AB  - Intracellular delivery of biologically active proteins remains a formidable
      challenge in biomedical research. Here we show that biomedically relevant enzymes
      can be delivered into cells using a new DNA transfection reagent, lipofectamine
      3000, allowing assessment of their intracellular functions. We also show that the
      J774.2 macrophage cell line exhibits unusual intracellular uptake of structurally
      and functionally distinct enzymes providing a convenient, reagent-free approach
      for evaluation of intracellular activities of enzymes. 

PMID- 26207615
TI  - Lithium Treatment in Patients With Huntington's Disease and Suicidal Behavior.

PMID- 26207614
TI  - Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with
      bevacizumab in first line treatment of metastatic colorectal cancer.
AB  - Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5
      fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in
      metastatic colorectal cancer (mCRC). Capecitabine is an orally administered
      fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We
      evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and
      irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified
      the maximum tolerated dose of irinotecan as 150 mg/m2. Median follow-up in a
      subsequent Phase II study using this dose was 28 months (74% progressed). For all
      patients, a complete response was achieved in 4% and a partial response in 60%;
      median progression-free survival (PFS) was 16 months and median overall survival
      (OS) was 28 months. Median PFS was longer for patients with an early treatment
      response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25
      vs. 9 months for others; P = 0.006), or for patients suitable for surgical
      removal of metastases with curative intent (median not reached vs. 9 months for
      others; P = 0.001). Median OS was longer for patients with early tumor shrinkage
      (median not reached vs. 22 months for others; P = 0.006) or surgery (median not
      reached vs. 22 months for others, P = 0.002). K-ras mutations status did not
      influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was
      encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In
      conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine,
      oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line
      treatment of mCRC, although at the expense of a high level of toxicity.

PMID- 26207616
TI  - Protective Effects of Caffeic Acid Phenethyl Ester on Cyclophosphamide-Induced
      Hemorrhagic Cystitis in Rats.
AB  - We investigated the protective effect of caffeic acid phenethyl ester (CAPE) on
      cyclophosphamide-induced hemorrhagic cystitis in rats in comparison with 2
      mercaptoethane sulfonate (MESNA). Forty male rats were randomized into four
      groups: group 1 (control), group 2 (cyclophosphamide), group 3 (cyclophosphamide
      + MESNA), group 4 (cyclophosphamide + CAPE). Cyclophosphamide injection increased
      malondialdehyde levels indicating oxidative stress, whereas CAPE and MESNA
      ameliorated malondialdehyde levels in the bladder (p < 0.05). Only catalase
      activities were decreased significantly in both groups (cyclophosphamide + MESNA
      and cyclophosphamide + CAPE, p < 0.05). Pretreatment with CAPE (p < 0.01)
      resulted in a significant decrease in nitric oxide levels when compared with the
      cyclophosphamide group. When we consider the studies that show the critical
      importance of increased nitric oxide levels in pathogenesis of cyclophosphamide
      induced hemorrhagic cystitis, we suggest that it would be more beneficial to use
      MESNA with CAPE to prevent histological damage. 

PMID- 26207617
TI  - Integrated genomic and functional analyses of histone demethylases identify
      oncogenic KDM2A isoform in breast cancer.
AB  - Histone lysine demethylases (KDMs) comprise a large class of enzymes that
      catalyze site-specific demethylation of lysine residues on histones and other
      proteins. They play critical roles in controlling transcription, chromatin
      architecture, and cellular differentiation. However, the genomic landscape and
      clinical significance of KDMs in breast cancer remain poorly characterized. Here,
      we conducted a meta-analysis of 24 KDMs in breast cancer and identified
      associations among recurrent copy number alterations, gene expression, breast
      cancer subtypes, and clinical outcome. Two KDMs, KDM2A and KDM5B, had the highest
      frequency of genetic amplification and overexpression. Furthermore, among the 24
      KDM genes, KDM2A had the highest correlation between copy number and mRNA
      expression, and high mRNA levels of KDM2A were significantly associated with
      shorter survival of breast cancer patients. KDM2A has two isoforms: the long
      isoform is comprised of a JmjC domain, CXXC-zinc finger, PHD zinc finger, F-box,
      and the AMN1 protein domain; whereas the short isoform of KDM2A lacks the N
      terminal JmjC domain but contains all other motifs. Detailed characterization of
      KDM2A in breast cancer revealed that the short isoform of KDM2A is more abundant
      than the long isoform at DNA, mRNA, and protein levels in a subset of breast
      cancers. Furthermore, our data indicate that the short isoform of KDM2A has
      oncogenic potential and functions as an oncogenic isoform in a subset of breast
      cancers. Taken together, our findings suggest that amplification and
      overexpression of the KDM2A short isoform is critical in breast cancer
      progression.

PMID- 26207618
TI  - Prevalence of celiac disease and celiac autoimmunity in the Toba Native
      Amerindian community of Argentina.
AB  - BACKGROUND: Celiac disease (CD) is mostly recognized among subjects with a
      Caucasian ethnic ancestry. No studies have explored conditions predisposing
      Amerindians to CD. OBJECTIVE: To prospectively assess environmental, genetic and
      serological conditions associated with CD among members of the Toba native
      population attending a multidisciplinary sanitary mission. METHODS: An expert
      nutritionist determined daily gluten intake using an established questionnaire.
      Gene typing for the human leukocyte antigen (HLA) class II alleles was performed
      on DNA extracted from peripheral blood (HLA DQ2/DQ8 haplotype). Serum antibodies
      were immunoglobulin (Ig) A tissue transglutaminase (tTG) and the composite
      deamidated gliadin peptides/tTG Screen test. Positive cases were tested for IgA
      endomysial antibodies. RESULTS: A total of 144 subjects (55% female) were
      screened. The estimated mean gluten consumption was 43 g/day (range 3 g/day to
      185 g/day). Genetic typing showed that 73 of 144 (50.7%) subjects had alleles
      associated with CD; 69 (94.5%) of these subjects had alleles for HLA DQ8 and four
      had DQ2 (5.5%). Four and six subjects had antibody concentrations above the cut
      off established by the authors' laboratory (>3 times the upper limit of normal)
      for IgA tTG and deamidated gliadin peptides/tTG screen, respectively. Four of
      these had concomitant positivity for both assays and endomysial antibodies were
      positive in three subjects who also presented a predisposing haplotype.
      CONCLUSION: The present study was the first to detect CD in Amerindians. The
      native Toba ethnic population has very high daily gluten consumption and a
      predisposing genetic background. We detected subjects with persistent CD
      autoimmunity and, at least, three of them fulfilled serological criteria for CD
      diagnosis.

PMID- 26207619
TI  - Identification and expression analysis of the LRR-RLK gene family in tomato
      (Solanum lycopersicum) Heinz 1706.
AB  - As the largest subfamily of receptor-like kinases (RLKs), leucine-rich repeat
      receptor-like kinases (LRR-RLKs) regulate the growth, development, and stress
      responses of plants. Through a reiterative process of sequence analysis and re
      annotation, 234 LRR-RLK genes were identified in the genome of tomato (Solanum
      lycopersicum) 'Heinz 1706', which were further grouped into 10 major groups based
      on their sequence similarity. In comparison to the significant role of tandem
      duplication in the expansion process of this gene family in other species, only
      approximately 12% (29 out of 234) of SlLRR-RLK genes arose from tandem
      duplication. Using the multiple expectation maximization for motif elicitation
      (MEME) method, the motif composition and arrangement were found to be variably
      conserved within each SlLRR-RLK group, indicating their different extent of
      functional divergence. Expression profiling analyses by qRT-PCR data revealed
      that SlLRR-RLK genes were differentially expressed in various tomato organs and
      tissues, and some SlLRR-RLK genes exhibited preferential expression in fruits at
      distinct developmental stages, suggesting that SlLRR-RLK may take important roles
      in fruit development and ripening process. The results of this study provide an
      overview of the LRR-RLK gene family in tomato Heinz 1706, one important species
      of Solanaceae, and will be helpful for future functional analysis of this
      important protein family in fleshy fruit-bearing species. 

PMID- 26207620
TI  - Self-Reported, Structured Measures of Recovery to Detect Postoperative Morbidity.
AB  - Previous studies have focused on postoperative anaesthetic visit as a tool for
      measuring postoperative recovery or patient's satisfaction. Whether it could also
      improve timely recognition of complications has not been studied yet. Aim of our
      study was to assess pathological findings in physical examination requiring
      further intervention during postoperative visit and to explore whether a self
      administered version of the Quality of Recovery (QoR)-9 score, compared to a
      detailed medical history, can act as a screening tool for identification of
      patients who show a low risk to develop postoperative complications. This
      observational study included 918 patients recovering from various types of non
      cardiac surgery and anaesthesia. The postoperative visit implied three steps:
      measuring the QoR-9 score, a structured medical history and a physical
      examination. QoR-9-score showed a comparable negative predictive value (0.93 vs.
      0.92) and a higher sensitivity of finding at least one pathological examination
      than a detailed medical history (0.92 vs. 0.81 respectively). At least one
      postoperative pathological examination finding was observed in 23.7% of the
      patients. Our approach presents a strategy on screening postoperative patients in
      order to identify patients whose examination and consequent treatment should be
      intensified. In further studies the question could be addressed whether the
      postoperative visit may help to reduce complications and mortality after surgery.

PMID- 26207621
TI  - A Standardized Precipitation Evapotranspiration Index Reconstruction in the Taihe
      Mountains Using Tree-Ring Widths for the Last 283 Years.
AB  - Tree-ring samples from Chinese Pine (Pinus tabulaeformis Carr.) that were
      collected in the Taihe Mountains on the western Loess Plateau, China, were used
      to analyze the effects of climate and drought on radial growth and to reconstruct
      the mean April-June Standardized Precipitation Evapotranspiration Index (SPEI)
      during the period 1730-2012 AD. Precipitation positively affected tree growth
      primarily during wet seasons, while temperature negatively affected tree growth
      during dry seasons. Tree growth responded positively to SPEI at long time scales
      most likely because the trees were able to withstand water deficits but lacked a
      rapid response to drought. The 10-month scale SPEI was chosen for further drought
      reconstruction. A calibration model for the period 1951-2011 explained 51% of the
      variance in the modeled SPEI data. Our SPEI reconstruction revealed long-term
      patterns of drought variability and captured some significant drought events,
      including the severe drought of 1928-1930 and the clear drying trend since the
      1950s which were widespread across northern China. The reconstruction was also
      consistent with two other reconstructions on the western Loess Plateau at both
      interannual and decadal scales. The reconstructed SPEI series showed synchronous
      variations with the drought/wetness indices and spatial correlation analyses
      indicated that this reconstruction could be representative of large-scale SPEI
      variability in northern China. Period analysis discovered 128-year, 25-year, 2.62
      year, 2.36-year, and 2.04-year cycles in this reconstruction. The time-dependency
      of the growth response to drought should be considered in further studies of the
      community dynamics. The SPEI reconstruction improves the sparse network of long
      term climate records for an enhanced understanding of climatic variability on the
      western Loess Plateau, China. 

PMID- 26207622
TI  - Association Study of Mannose-Binding Lectin Levels and Genetic Variants in Lectin
      Pathway Proteins with Susceptibility to Age-Related Macular Degeneration: A Case
      Control Study.
AB  - BACKGROUND: In age-related macular degeneration (AMD) the complement system is
      thought to be activated by chronic oxidative damage with genetic variants
      identified in the alternative pathway as susceptibility factors. However, the
      involvement of the lectin pathway of complement, a key mediator of oxidative
      damage, is controversial. This study investigated whether mannose-binding lectin
      (MBL) levels and genetic variants in lectin pathway proteins, are associated with
      the predisposition to and severity of AMD. METHODS: MBL levels and single
      nucleotide polymorphisms (SNPs) in the MBL2 and the ficolin-2 (FCN2) gene were
      determined in 109 patients with AMD and 109 age- and sex-matched controls.
      RESULTS: MBL expression levels were equally distributed in both cases (early and
      late AMD) and controls (p>0.05). However, there was a trend towards higher median
      MBL levels in cases with late AMD compared to cases with early AMD (1.0 vs. 0.4
      MUg/ml, p = 0.09) and MBL deficiency (<0.5 MUg/ml) was encountered less
      frequently in the late AMD group (35% vs 56%, p = 0.03). FCN2 and MBL2 allele
      frequencies were similarly distributed in early and late AMD cases compared with
      controls (p>0.05 for all analyses) as were MBL2 genotypes. Similarly, there was
      no significant difference in allele frequencies in any SNPs in either the MBL2 or
      FCN2 gene in cases with early vs. late AMD. CONCLUSIONS: SNPs of lectin pathway
      proteins investigated in this study were not associated with AMD or AMD severity.
      However, MBL levels deserve further study in a larger cohort of early vs. late
      AMD patients to elucidate any real effect on AMD severity.

PMID- 26207624
TI  - Correction: How Lovebirds Maneuver Rapidly Using Super-Fast Head Saccades and
      Image Feature Stabilization.

PMID- 26207623
TI  - Effects of Lumbosacral Spinal Cord Epidural Stimulation for Standing after
      Chronic Complete Paralysis in Humans.
AB  - Sensory and motor complete spinal cord injury (SCI) has been considered
      functionally complete resulting in permanent paralysis with no recovery of
      voluntary movement, standing or walking. Previous findings demonstrated that
      lumbosacral spinal cord epidural stimulation can activate the spinal neural
      networks in one individual with motor complete, but sensory incomplete SCI, who
      achieved full body weight-bearing standing with independent knee extension,
      minimal self-assistance for balance and minimal external assistance for
      facilitating hip extension. In this study, we showed that two clinically sensory
      and motor complete participants were able to stand over-ground bearing full body
      weight without any external assistance, using their hands to assist balance. The
      two clinically motor complete, but sensory incomplete participants also used
      minimal external assistance for hip extension. Standing with the least amount of
      assistance was achieved with individual-specific stimulation parameters, which
      promoted overall continuous EMG patterns in the lower limbs' muscles. Stimulation
      parameters optimized for one individual resulted in poor standing and additional
      need of external assistance for hip and knee extension in the other participants.
      During sitting, little or negligible EMG activity of lower limb muscles was
      induced by epidural stimulation, showing that the weight-bearing related sensory
      information was needed to generate sufficient EMG patterns to effectively support
      full weight-bearing standing. In general, electrode configurations with cathodes
      selected in the caudal region of the array at relatively higher frequencies (25
      60 Hz) resulted in the more effective EMG patterns for standing. These results
      show that human spinal circuitry can generate motor patterns effective for
      standing in the absence of functional supraspinal connections; however the
      appropriate selection of stimulation parameters is critical. 

PMID- 26207625
TI  - Cell Fusion along the Anterior-Posterior Neuroaxis in Mice with Experimental
      Autoimmune Encephalomyelitis.
AB  - BACKGROUND: It is well documented that bone marrow-derived cells can fuse with a
      diverse range of cells, including brain cells, under normal or pathological
      conditions. Inflammation leads to robust fusion of bone marrow-derived cells with
      Purkinje cells and the formation of binucleate heterokaryons in the cerebellum.
      Heterokaryons form through the fusion of two developmentally differential cells
      and as a result contain two distinct nuclei without subsequent nuclear or
      chromosome loss. AIM: In the brain, fusion of bone marrow-derived cells appears
      to be restricted to the complex and large Purkinje cells, raising the question
      whether the size of the recipient cell is important for cell fusion in the
      central nervous system. Purkinje cells are among the largest neurons in the
      central nervous system and accordingly can harbor two nuclei. RESULTS: Using a
      well-characterized model for heterokaryon formation in the cerebellum
      (experimental autoimmune encephalomyelitis - a mouse model of multiple
      sclerosis), we report for the first time that green fluorescent protein-labeled
      bone marrow-derived cells can fuse and form heterokaryons with spinal cord motor
      neurons. These spinal cord heterokaryons are predominantly located in or adjacent
      to an active or previously active inflammation site, demonstrating that
      inflammation and infiltration of immune cells are key for cell fusion in the
      central nervous system. While some motor neurons were found to contain two
      nuclei, co-expressing green fluorescent protein and the neuronal marker, neuron
      specific nuclear protein, a number of small interneurons also co-expressed green
      fluorescent protein and the neuronal marker, neuron-specific nuclear protein.
      These small heterokaryons were scattered in the gray matter of the spinal cord.
      CONCLUSION: This novel finding expands the repertoire of neurons that can form
      heterokaryons with bone marrow-derived cells in the central nervous system,
      albeit in low numbers, possibly leading to a novel therapy for spinal cord motor
      neurons or other neurons that are compromised in the central nervous system.

PMID- 26207626
TI  - A Quantitative Profiling Tool for Diverse Genomic Data Types Reveals Potential
      Associations between Chromatin and Pre-mRNA Processing.
AB  - High-throughput sequencing, and genome-based datasets in general, are often
      represented as profiles centered at reference points to study the association of
      protein binding and other signals to particular regulatory mechanisms. Although
      these profiles often provide compelling evidence of these associations, they do
      not provide a quantitative assessment of the enrichment, which makes the
      comparison between signals and conditions difficult. In addition, a number of
      biases can confound profiles, but are rarely accounted for in the tools currently
      available. We present a novel computational method, ProfileSeq, for the
      quantitative assessment of biological profiles to provide an exact, nonparametric
      test that specific regions of the test profile have higher or lower signal
      densities than a control set. The method is applicable to high-throughput
      sequencing data (ChIP-Seq, GRO-Seq, CLIP-Seq, etc.) and to genome-based datasets
      (motifs, etc.). We validate ProfileSeq by recovering and providing a quantitative
      assessment of several results reported before in the literature using independent
      datasets. We show that input signal and mappability have confounding effects on
      the profile results, but that normalizing the signal by input reads can eliminate
      these biases while preserving the biological signal. Moreover, we apply
      ProfileSeq to ChIP-Seq data for transcription factors, as well as for motif and
      CLIP-Seq data for splicing factors. In all examples considered, the profiles were
      robust to biases in mappability of sequencing reads. Furthermore, analyses
      performed with ProfileSeq reveal a number of putative relationships between
      transcription factor binding to DNA and splicing factor binding to pre-mRNA,
      adding to the growing body of evidence relating chromatin and pre-mRNA
      processing. ProfileSeq provides a robust way to quantify genome-wide coordinate
      based signal. Software and documentation are freely available for academic use at
      https://bitbucket.org/regulatorygenomicsupf/profileseq/. 

PMID- 26207627
TI  - Enrichment of Minor Alleles of Common SNPs and Improved Risk Prediction for
      Parkinson's Disease.
AB  - Parkinson disease (PD) is the second most common neurodegenerative disorder in
      the aged population and thought to involve many genetic loci. While a number of
      individual single nucleotide polymorphisms (SNPs) have been linked with PD, many
      remain to be found and no known markers or combinations of them have a useful
      predictive value for sporadic PD cases. The collective effects of genome wide
      minor alleles of common SNPs, or the minor allele content (MAC) in an individual,
      have recently been shown to be linked with quantitative variations of numerous
      complex traits in model organisms with higher MAC more likely linked with lower
      fitness. Here we found that PD cases had higher MAC than matched controls. A set
      of 37564 SNPs with MA (MAF < 0.4) more common in cases (P < 0.05) was found to
      have the best predictive accuracy. A weighted risk score calculated by using this
      set can predict 2% of PD cases (100% specificity), which is comparable to using
      familial PD genes to identify familial PD cases. These results suggest a novel
      genetic component in PD and provide a useful genetic method to identify a small
      fraction of PD cases. 

PMID- 26207628
TI  - Urban Transfer Entropy across Scales.
AB  - The morphology of urban agglomeration is studied here in the context of
      information exchange between different spatio-temporal scales. Urban migration to
      and from cities is characterised as non-random and following non-random pathways.
      Cities are multidimensional non-linear phenomena, so understanding the
      relationships and connectivity between scales is important in determining how the
      interplay of local/regional urban policies may affect the distribution of urban
      settlements. In order to quantify these relationships, we follow an information
      theoretic approach using the concept of Transfer Entropy. Our analysis is based
      on a stochastic urban fractal model, which mimics urban growing settlements and
      migration waves. The results indicate how different policies could affect urban
      morphology in terms of the information generated across geographical scales. 

PMID- 26207629
TI  - 1,8-Cineol Reduces Mucus-Production in a Novel Human Ex Vivo Model of Late
      Rhinosinusitis.
AB  - Inflammatory diseases of the respiratory system such as rhinosinusitis, chronic
      obstructive pulmonary disease, or bronchial asthma are strongly associated with
      overproduction and hypersecretion of mucus lining the epithelial airway surface.
      1,8-cineol, the active ingredient of the pharmaceutical drug Soledum, is commonly
      applied for treating such inflammatory airway diseases. However, its potential
      effects on mucus overproduction still remain unclear.In the present study, we
      successfully established ex vivo cultures of human nasal turbinate slices to
      investigate the effects of 1,8-cineol on mucus hypersecretion in experimentally
      induced rhinosinusitis. The presence of acetyl-alpha-tubulin-positive cilia
      confirmed the integrity of the ex vivo cultured epithelium. Mucin-filled goblet
      cells were also detectable in nasal slice cultures, as revealed by Alcian Blue
      and Periodic acid-Schiff stainings. Treatment of nasal slice cultures with
      lipopolysaccharides mimicking bacterial infection as observed during late
      rhinosinusitis led to a significantly increased number of mucin-filled goblet
      cells. Notably, the number of mucin-filled goblet cells was found to be
      significantly decreased after co-treatment with 1,8-cineol. On a molecular level,
      real time PCR-analysis further showed 1,8-cineol to significantly reduce the
      expression levels of the mucin genes MUC2 and MUC19 in close association with
      significantly attenuated NF-kappaB-activity. In conclusion, we demonstrate for
      the first time a 1,8-cineol-dependent reduction of mucin-filled goblet cells and
      MUC2-gene expression associated with an attenuated NF-kappaB-activity in human
      nasal slice cultures. Our findings suggest that these effects partially account
      for the clinical benefits of 1,8-cineol-based therapy during rhinosinusitis.
      Therefore, topical application of 1,8-cineol may offer a novel therapeutic
      approach to reduce bacteria-induced mucus hypersecretion. 

PMID- 26207630
TI  - Antituberculosis Drug Resistance Survey in Lesotho, 2008-2009: Lessons Learned.
AB  - SETTING: Drug resistance is an increasing threat to tuberculosis (TB) control
      worldwide. The World Health Organization advises monitoring for drug resistance,
      with either ongoing surveillance or periodic surveys. METHODS: The
      antituberculosis drug resistance survey was conducted in Lesotho in 2008-2009.
      Basic demographic and TB history information was collected from individuals with
      positive sputum smear results at 17 diagnostic facilities. Additional sputum
      sample was sent to the national TB reference laboratory for culture and drug
      susceptibility testing. RESULTS: Among 3441 eligible smear-positive persons, 1121
      (32.6%) were not requested to submit sputum for culture. Among 2320 persons
      submitted sputum, 1164 (50.2%) were not asked for clinical information or did not
      have valid sputum samples for testing. In addition, 445/2320 (19.2%) were
      excluded from analysis because of other laboratory or data management reasons.
      Among 984/3441 (28.6%) persons who had data available for analysis, MDR-TB was
      present in 24/773 (3.1%) of new and 25/195 (12.8%) of retreatment TB cases.
      Logistical, operational and data management challenges affected survey results.
      CONCLUSION: MDR-TB is prevalent in Lesotho, but limitations reduced the
      reliability of our findings. Multiple lessons learned during this survey can be
      applied to improve the next drug resistance survey in Lesotho and other resource
      constrained countries may learn how to avoid these bottlenecks.

PMID- 26207631
TI  - Mapping Systemic Risk: Critical Degree and Failures Distribution in Financial
      Networks.
AB  - The financial crisis illustrated the need for a functional understanding of
      systemic risk in strongly interconnected financial structures. Dynamic processes
      on complex networks being intrinsically difficult to model analytically, most
      recent studies of this problem have relied on numerical simulations. Here we
      report analytical results in a network model of interbank lending based on
      directly relevant financial parameters, such as interest rates and leverage
      ratios. We obtain a closed-form formula for the "critical degree" (the number of
      creditors per bank below which an individual shock can propagate throughout the
      network), and relate failures distributions to network topologies, in particular
      scalefree ones. Our criterion for the onset of contagion turns out to be
      isomorphic to the condition for cooperation to evolve on graphs and social
      networks, as recently formulated in evolutionary game theory. This remarkable
      connection supports recent calls for a methodological rapprochement between
      finance and ecology. 

PMID- 26207632
TI  - Obif, a Transmembrane Protein, Is Required for Bone Mineralization and
      Spermatogenesis in Mice.
AB  - BACKGROUND: Various kinds of transmembrane and secreted proteins play pivotal
      roles in development through cell-cell communication. We previously reported that
      Obif (Osteoblast induction factor, Tmem119), encoding a single transmembrane
      protein, is expressed in differentiating osteoblasts, and that Obif-/- mice
      exhibit significantly reduced bone volume in the femur. In the current study, we
      characterized the Obif protein and further investigated the biological phenotypes
      of a variety of tissues in Obif-/- mice. RESULTS: First, we found that O
      glycosylation of the Obif protein occurs at serine residue 36 in the Obif
      extracellular domain. Next, we observed that Obif-/- mice exhibit bone dysplasia
      in association with significantly increased osteoid volume per osteoid surface
      (OV/OS) and osteoid maturation time (Omt), and significantly decreased mineral
      apposition rate (MAR) and bone formation rate per bone surface (BFR/BS). In
      addition, we observed that Obif-/- mice show a significant decrease in testis
      weight as well as in sperm number. By histological analysis, we found that Obif
      is expressed in spermatocytes and spermatids in the developing testis and that
      spermatogenesis is halted at the round spermatid stage in the Obif-/- testis that
      lacks sperm. However, the number of litters fathered by male mice was slightly
      reduced in Obif-/- mice compared with wild-type mice, although this was not
      statistically significant. CONCLUSIONS: Our results, taken together with previous
      observations, indicate that Obif is a type Ia transmembrane protein whose N
      terminal region is O-glycosylated. In addition, we found that Obif is required
      for normal bone mineralization and late testicular differentiation in vivo. These
      findings suggest that Obif plays essential roles in the development of multiple
      tissues.

PMID- 26207633
TI  - Overlap Chronic Placental Inflammation Is Associated with a Unique Gene
      Expression Pattern.
AB  - Breakdown of the balance between maternal pro- and anti-inflammatory pathways is
      thought to allow an anti-fetal maternal immune response that underlies
      development of chronic placental inflammation. Chronic placental inflammation is
      manifested by the influx of maternal inflammatory cells, including lymphocytes,
      histiocytes, and plasma cells, into the placental membranes, villi, and decidua.
      These infiltrates are recognized pathologically as chronic chorioamnionitis,
      chronic villitis of unknown etiology, and chronic deciduitis. Each of these
      histological entities is associated with adverse fetal outcomes including
      intrauterine growth restriction and preterm birth. Studying the gene expression
      patterns in chronically inflamed placenta, particularly when overlapping
      histologies are present, may lead to a better understanding of the underlying
      mechanism(s). Therefore, this study compared tissue with and without chronic
      placental inflammation, manifested as overlapping chronic chorioamnionitis,
      chronic villitis of unknown etiology, and chronic deciduitis. RNA expression
      profiling was conducted on formalin fixed, paraffin embedded placental tissue
      using Illumina microarrays. IGJ was the most significant differentially expressed
      gene identified and had increased expression in the inflamed tissue. In addition,
      IGLL1, CXCL13, CD27, CXCL9, ICOS, and KLRC1 had increased expression in the
      inflamed placental samples. These differentially expressed genes are associated
      with T follicular helper cells, natural killer cells, and B cells. Furthermore,
      these genes differ from those typically associated with the individual components
      of chronic placental inflammation, such as chronic villitis, suggesting that the
      inflammatory infiltrate associated with overlapping chronic chorioamnionitis,
      chronic villitis of unknown etiology, and chronic deciduitis differs is unique.
      To further explore and validate gene expression findings, we conducted
      immunohistochemical assessment of protein level expression and demonstrate that
      IgJ expression was largely attributable to the presence of plasma cells as part
      of chronic deciduitis and that IgA positive plasma cells are associated with
      chronic deciduitis occurring in combination with chronic chorioamnionitis and
      chronic villitis of unknown etiology but not with isolated chronic deciduitis. 

PMID- 26207634
TI  - Specklinia dunstervillei, a New Species Long Confused with Specklinia endotrachys
      (Orchidaceae: Pleurothallidinae).
AB  - Specklinia dunstervillei is described as a new species in recognition of the
      distinctness of a Venezuelan species related to and confused with Specklinia
      endotrachys. It was illustrated for the first time by G. C. K. Dunsterville in
      1963 from a plant collected in Trujillo on the Cordillera de Merida. The newly
      named species can be easily recognized by its small habit, short leaves and small
      reddish-orange flowers, the non-ascending dorsal sepal and the obtuse petals that
      are shortly apiculate. Specklinia dunstervillei is formally described and
      illustrated once again and compared morphologically and genetically with its
      closest relatives. 

PMID- 26207635
TI  - Rapid, Simple and Cost-Effective Molecular Method to Differentiate the
      Temperature Sensitive (ts+) MS-H Vaccine Strain and Wild-Type Mycoplasma synoviae
      Isolates.
AB  - Mycoplasma synoviae infection in chickens and turkeys can cause respiratory
      disease, infectious synovitis and eggshell apex abnormality; thus it is an
      economically important pathogen. Control of M. synoviae infection comprises
      eradication, medication or vaccination. The differentiation of the temperature
      sensitive (ts+) MS-H vaccine strain from field isolates is crucial during
      vaccination programs. Melt-curve and agarose gel based mismatch amplification
      mutation assays (MAMA) are provided in the present study to distinguish between
      the ts+ MS-H vaccine strain, its non-temperature sensitive re-isolates and wild
      type M. synoviae isolates based on the single nucleotide polymorphisms at nt367
      and nt629 of the obg gene. The two melt-MAMAs and the two agarose-MAMAs clearly
      distinguish the ts+ MS-H vaccine strain genotype from its non-temperature
      sensitive re-isolate genotype and wild-type M. synoviae isolate genotype, and no
      cross-reactions with other Mycoplasma species infecting birds occur. The
      sensitivity of the melt-MAMAs and agarose-MAMAs was 103 and 104 copy numbers,
      respectively. The assays can be performed directly on clinical samples and they
      can be run simultaneously at the same annealing temperature. The assays can be
      performed in laboratories with limited facilities, using basic real-time PCR
      machine or conventional thermocycler coupled with agarose gel electrophoresis.
      The advantages of the described assays compared with previously used methods are
      simplicity, sufficient sensitivity, time and cost effectiveness and specificity. 

PMID- 26207636
TI  - Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal
      Transition in Inflammatory Breast Cancer Cells.
AB  - Inflammatory breast cancer (IBC) is the most insidious form of locally advanced
      breast cancer; about a third of patients have distant metastasis at initial
      staging. Emerging evidence suggests that host factors in the tumor
      microenvironment may interact with underlying IBC cells to make them aggressive.
      It is unknown whether immune cells associated to the IBC microenvironment play a
      role in this scenario to transiently promote epithelial to mesenchymal transition
      (EMT) in these cells. We hypothesized that soluble factors secreted by activated
      immune cells can induce an EMT in IBC and thus promote metastasis. In a pilot
      study of 16 breast cancer patients, TNF-alpha production by peripheral blood T
      cells was correlated with the detection of circulating tumor cells expressing EMT
      markers. In a variety of IBC model cell lines, soluble factors from activated T
      cells induced expression of EMT-related genes, including FN1, VIM, TGM2, ZEB1.
      Interestingly, although IBC cells exhibited increased invasion and migration
      following exposure to immune factors, the expression of E-cadherin (CDH1), a cell
      adhesion molecule, increased uniquely in IBC cell lines but not in non-IBC cell
      lines. A combination of TNF-alpha, IL-6, and TGF-beta was able to recapitulate
      EMT induction in IBC, and conditioned media preloaded with neutralizing
      antibodies against these factors exhibited decreased EMT. These data suggest that
      release of cytokines by activated immune cells may contribute to the
      aggressiveness of IBC and highlight these factors as potential target mediators
      of immune-IBC interaction. 

PMID- 26207637
TI  - Impact of Prior Abdominal Surgery on Rates of Conversion to Open Surgery and
      Short-Term Outcomes after Laparoscopic Surgery for Colorectal Cancer.
AB  - PURPOSE: To evaluate the impact of prior abdominal surgery (PAS) on rates of
      conversion to open surgery and short-term outcomes after laparoscopic surgery for
      colon and rectal cancers. METHODS: We compared three groups as follows: colon
      cancer patients with no PAS (n = 272), major PAS (n = 24), and minor PAS (n =
      33), and rectal cancer patients with no PAS (n = 282), major PAS (n=16), and
      minor PAS (n = 26). RESULTS: In patients with colon and rectal cancers, the rate
      of conversion to open surgery was significantly higher in the major PAS group
      (25% and 25%) compared with the no PAS group (8.1% and 8.9%), while the
      conversion rate was similar between the no PAS and minor PAS groups (15.2% and
      15.4%). The 30-day complication rate did not differ among the three groups (28.7%
      and 29.1% in the no PAS group, 29.2% and 25% in the major PAS group, and 27.3%
      and 26.9% in the minor PAS group). The mean operative time did not differ among
      the three groups (188 min and 227 min in the no PAS group, 191 min and 210 min in
      the major PAS group, and 192 min and 248 min in the minor PAS group). The rate of
      conversion to open surgery was significantly higher in patients with prior
      gastrectomy or colectomy compared with the no PAS group, while the conversion
      rate was similar between the no PAS group and patients with prior radical
      hysterectomy in patients with colon and rectal cancers. CONCLUSIONS: Our results
      suggest that colorectal cancer patients with minor PAS or patients with prior
      radical hysterectomy can be effectively managed with a laparoscopic approach. In
      addition, laparoscopy can be selected as the primary surgical approach even in
      patients with major PAS (prior gastrectomy or colectomy) given the assumption of
      a higher conversion rate.

PMID- 26207638
TI  - Genetic Susceptibility Is One of the Determinants for Severe Fever with
      Thrombocytopenia Syndrome Virus Infection and Fatal Outcome: An Epidemiological
      Investigation.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious
      disease in China and case-fatality rate of SFTS is very high (approximately 10%).
      However, genetic susceptibility for SFTS virus (SFTSV) infection and fatal
      outcome of SFTSV infection in humans are unclear. In this study, we investigated
      the clinical, laboratory and epidemiological features of SFTS in a cluster of
      three sisters who died of SFTSV infection between late April and mid-May 2014.
      Before disease onset, two of the sisters (Case A and case B) had common exposure
      history for ticks by working together in a field to pick tea leaves from April 8
      to April 12. The third sister (Case C) did not live or work together with case A
      and B, but had ticks in her living environment. SFTSV RNA sequences were
      amplified from three cases were not identical, suggesting that the three sisters
      were most likely infected with SFTSV through tick bite rather than through person
      to-person transmission of SFTSV. The sequence of SFTSV from case C was identical
      to SFTSV sequences from 3 groups of ticks collected around the residential area
      of case C. Seroprevalence of SFTSV IgG antibody among healthy population in the
      area where the patients resided was 4.05% (3/74). The majority of SFTSV
      infections were mild cases and all three sisters died of SFTSV infection
      suggested that they were highly susceptible to SFTSV. Our findings indicated that
      genetic susceptibility was a risk factor for SFTSV infection and fatal outcome. 

PMID- 26207639
TI  - Reasons and Risk Factors for the Initial Regimen Modification in Chinese
      Treatment-Naive Patients with HIV Infection: A Retrospective Cohort Analysis.
AB  - BACKGROUND: To investigate the reasons and risk factors for modification of the
      first combined antiretroviral therapy (cART) currently used for HIV infected
      patients who were treatment naive in Shanghai China. METHODS: Making a
      retrospective observational research on treatment naive patients with HIV
      infection who initiated cART during the period of September 1st 2005---December
      1st 2013. The demographic and clinical data were collected from the first visit
      to the time of the first regimen modification or the last visit in December 1st,
      2014. The reasons of treatment modification were recorded. Survival analysis of
      modification was made by Kaplan-Meier curves analysis and log rank test, and a
      Cox multiple regression model was constructed to identify related factors of
      modification. RESULTS: A total number of the eligible participants were 3372 and
      871(25.8%) patients changed their first cART regimen. The median follow up was 22
      months [interquartile range (IQR) 14-39]. Among patients who modified the
      original regimen, drug toxicity occurred in 805(92.4%) participants and 44(5.1%)
      experienced treatment failure. In multiple regression analysis regimen
      modification was associated with patients' age more than 40 years old (aHR 1.224,
      95%CI 1.051-1.426, P = 0.010), CD4 less than 200(aHR 1.218, 95%CI 1.044-1.421, P
      = 0.012) and the initial regimen they received. Compared with the regimen of
      TDF+3TC+EFV, patients with regimen of d4T+3TC+NVP, d4T+3TC+EFV, AZT+3TC+NVP or
      AZT+3TC+EFV were 10.4, 8.2, 6.4, 2.5 times more likely to modify their initial
      regimen, respectively. CONCLUSIONS: The main reason for the regimen switch was
      drug toxicity and main risk factors for regimen modification were age older than
      40 years, CD4 cell counts less than 200 at baseline and regimen they received.
      Among the 2NRTI plus 1NNRTI regimens, the co-formulation of d4T+3TC+NVP had the
      highest risk for modification while the regimen of TDF+3TC+EFV was the most
      tolerable treatment regimen in first years' follow up.

PMID- 26207642
TI  - Gleason score 5 + 3 = 8 prostate cancer: much more like Gleason score 9?
AB  - OBJECTIVE: To determine whether patients with Gleason score 5 + 3 = 8 prostate
      cancer have outcomes more similar to other patients with Gleason score 8 disease
      or to patients with Gleason score 9 disease. PATIENTS AND METHODS: The
      Surveillance, Epidemiology and End Results (SEER) database was used to study 40
      533 men diagnosed with N0M0 Gleason score 8 or 9 prostate cancer from 2004 to
      2011. Using Gleason score 4 + 4 = 8 as the referent, Fine and Gray competing
      risks regression analyses modelled the association between Gleason score and
      prostate cancer-specific mortality (PCSM). RESULTS: The 5-year PCSM rates for
      patients with Gleason score 4 + 4 = 8, 3 + 5 = 8, 5 + 3 = 8, and 9 disease were
      6.3%, 6.6%, 13.5%, and 13.9%, respectively (P < 0.001). Patients with Gleason
      score 5 + 3 = 8 or 9 disease had up to a two-fold increased risk of PCSM
      (adjusted hazard ratio [AHR] 1.89, 95% confidence interval [CI] 1.50-2.38, P <
      0.001; and AHR 2.17, 95% CI 1.99-2.36, P < 0.001, respectively) compared with the
      referent group of patients (Gleason score 4 + 4 = 8). There was no difference in
      PCSM between patients with Gleason score 5 + 3 = 8 vs 9 disease (P = 0.25).
      CONCLUSIONS: Gleason score 8 disease represents a heterogeneous entity with PCSM
      outcomes distinguishable by the primary Gleason pattern. The PCSM of Gleason
      score 3 + 5 = 8 and Gleason 4 + 4 = 8 disease are similar, but patients with
      Gleason score 5 + 3 = 8 have a risk of PCSM that is twice as high as other
      patients with Gleason score 8 disease and should be considered to have a similar
      poor prognosis as patients with Gleason score 9 disease. Such patients should be
      allowed onto trials seeking the highest-risk patients in which to test novel
      aggressive treatment strategies.

PMID- 26207643
TI  - Clinical phenotype in genetically confirmed von Willebrand disease type 2N
      patients reflects a haemophilia A phenotype.
AB  - INTRODUCTION: Von Willebrand disease (VWD) type 2N is characterized by a
      defective binding of factor VIII (FVIII) to von Willebrand factor (VWF) resulting
      in diminished plasma FVIII levels and a clinical phenotype mimicking mild
      haemophilia A. Several mutations in the FVIII binding site of VWF have been
      reported. AIM: This study aims to examine the effect of genotype on clinical
      phenotype in a cohort of VWD 2N patients. METHODS: Patients with at least one
      genetically confirmed 2N mutation were selected retrospectively from a cohort of
      patients with suspected VWD. Clinical and laboratory phenotypes including
      bleeding scores (BS) were obtained and analysed. RESULTS: Forty-two VWD 2N
      patients with a mean age of 44 years were included. Eleven patients were
      homozygous or compound heterozygous (genetically confirmed group) and 31 patients
      were heterozygously affected (carriers group). Statistically significant
      differences between genetically confirmed VWD 2N patients and carriers were found
      in FVIII activity, VWF antigen levels, VWF-FVIII binding capacity, FVIII/VWF
      antigen ratio (all P<0.001), VWF-ristocetin activity (p=0.001) and VWF collagen
      binding (P = 0.002). Median BS was 6 in genetically confirmed VWD 2N patients
      compared with 3 in carriers (P = 0.047). Haemarthrosis, muscle haematomas and
      postpartum haemorrhage were only reported in genetically confirmed 2N patients.
      CONCLUSION: Phenotypic analysis showed that all laboratory parameters are lower
      in genetically confirmed VWD 2N patients compared with heterozygous 2N carriers.
      The clinical phenotype in genetically confirmed VWD 2N patients is comparable to
      mild haemophilia A patients and more severe than heterozygous 2N carriers.

PMID- 26207644
TI  - Risk Factors for Sudden Cardiac Death Among Patients with Alcohol Dependence: A
      Nested Case-Control Study.
AB  - BACKGROUND: Excessive alcohol consumption causes a broad range of health
      problems, including premature mortality and sudden cardiac death (SCD). We
      identified potential clinical characteristics and laboratory indices associated
      with SCD among patients with alcohol dependence. METHODS: Patients with alcohol
      dependence (n = 2,793) admitted to a psychiatric center in northern Taiwan
      between 1985 and 2008 were linked with a national mortality database for causes
      of death. Of the 2,793 patients in the cohort, 67 cases died of SCD. The
      standardized mortality ratio (SMR) of SCD relative to the general population was
      calculated. Based on a nested case-control design, we selected a set of sex-, age
      , and year-of-admission-matched two control subjects for each case derived from
      the cohort. We collated the clinical information through a standardized review of
      patients' medical records. Conditional logistic regressions were then conducted
      to explore potential exposures associated with SCD. RESULTS: The sample had
      substantially higher SCD mortality (SMR 12.8) compared to the general population.
      After adjustments in the multivariate analyses for the clinical profiles at the
      index (earliest) admission, both abnormal electrocardiography (ECG) (adjusted
      risk ratio = 16.97, 95% confidence interval (CI) 1.60 to 179.58, p = 0.019) and
      elevated aspartate aminotransferase levels (adjusted risk ratio = 1.01, 95% CI
      1.00 to 1.02, p = 0.046) were significantly associated with SCD. CONCLUSIONS:
      This study raises the question of whether intensive follow-up of patients with
      elevated AST and abnormal ECG findings should be evaluated as a strategy to
      prevent SCD in patients with alcohol dependence.

PMID- 26207645
TI  - In Silico Approach To Identify Potential Thyroid Hormone Disruptors among
      Currently Known Dust Contaminants and Their Metabolites.
AB  - Thyroid hormone disrupting chemicals (THDCs) interfere with the thyroid hormone
      system and may induce multiple severe physiological disorders. Indoor dust
      ingestion is a major route of THDCs exposure in humans, and one of the molecular
      targets of these chemicals is the hormone transporter transthyretin (TTR). To
      virtually screen indoor dust contaminants and their metabolites for THDCs
      targeting TTR, we developed a quantitative structure-activity relationship (QSAR)
      classification model. The QSAR model was applied to an in-house database
      including 485 organic dust contaminants reported from literature data and their
      433 in silico derived metabolites. The model predicted 37 (7.6%) dust
      contaminants and 230 (53.1%) metabolites as potential TTR binders. Four new THDCs
      were identified after testing 23 selected parent dust contaminants in a radio
      ligand TTR binding assay; 2,2',4,4'-tetrahydroxybenzophenone,
      perfluoroheptanesulfonic acid, 3,5,6-trichloro-2-pyridinol, and 2,4,5
      trichlorophenoxyacetic acid. These chemicals competitively bind to TTR with 50%
      inhibition (IC50) values at or below 10 MUM. Molecular docking studies suggested
      that these THDCs interacted similarly with TTR via the residue Ser117A, but their
      binding poses were dissimilar to the endogenous ligand T4. This study identified
      new THDCs using an in silico approach in combination with bioassay testing and
      highlighted the importance of metabolic activation for TTR binding.

PMID- 26207646
TI  - U.S. Public Health Service Response to the 2014-2015 Ebola Epidemic in West
      Africa: A Nursing Perspective.
AB  - The 2014-2015 Ebola epidemic in West Africa has been the deadliest Ebola epidemic
      to date. In response to this deadly epidemic, the U.S. government declared this a
      top national security priority and members of the Commissioned Corps of the
      United States Public Health Service were tasked to provide direct patient care to
      Ebola virus disease patients. Commissioned Corps nurses provided the highest
      level of care under the most austere conditions. This article discusses the
      training, ethical dilemmas, and constant risk for potential exposure while
      working in an Ebola Treatment Unit. 

PMID- 26207648
TI  - Thermally activated delayed fluorescence with circularly polarized luminescence
      characteristics.
AB  - A metal-free aromatic compound with a chiral carbon sandwiched between a donor
      moiety and an acceptor moiety was designed. Under thermally activated delayed
      fluorescence, the compound displayed a photoluminescence quantum yield of 26%,
      and showed circularly polarized luminescence with a dissymmetry factor of 10(-3).

PMID- 26207647
TI  - Elevated Serum Gas6 Is a Novel Prognostic Biomarker in Patients with Oral
      Squamous Cell Carcinoma.
AB  - OBJECTIVE: This study explored the level and clinical significance of serum Gas6
      in patients with oral squamous cell carcinoma (OSCC). METHODS: A total of 128
      OSCC patients and 145 normal controls were selected. Enzyme-linked immunosorbent
      assay was used to detect Gas6 concentration in sera from the OSCC patients and
      controls. The correlations of serum Gas6 concentration and clinicopathological
      characteristics of OSCC patients were assessed, and the prognostic significance
      of serum Gas6 was evaluated with a Kaplan-Meier curve and log-rank test. RESULTS:
      The results showed that serum Gas6 concentration was significantly higher in OSCC
      patients than in controls (P < 0.05). OSCC patients with late TNM stage (III, IV)
      had a relatively high serum Gas6 concentration compared with those with early
      stage (I, II) (P < 0.01) and patients with poorly differentiated tumors had a
      higher level of serum Gas6 than those with well-differentiated tumors (P < 0.01).
      Multivariate logistic regression analysis demonstrated that high serum Gas6 was
      an independent risk factor for lymph nodal metastases in OSCC patients (OR =
      2.79, 95% CI: 1.72-4.48). For predicting OSCC development, ROC curve analysis
      showed a sensitivity of 0.63 with a specificity of 0.92 (AUC = 0.79, 95% CI: 0.74
      0.85). Cox analysis revealed that high serum Gas6 was an independent biomarker
      for predicting poor overall survival in OSCC patients (HR = 2.07, 95% CI: 1.79
      3.62). In addition, we found that Gas6 expression was increased in OSCC tissues
      and it may significantly decrease E-cadherin expression, and increase P-cadherin
      and N-cadherin expression, in OSCC cells. Further, Gas6 could promote the
      migratory and invasive ability of OSCC cells in vitro. CONCLUSION: Taken
      together, these results suggest that Gas6 increases the metastatic capacity of
      OSCC cells and serum Gas6 could be a candidate biomarker for diagnostic and
      prognostic use in OSCC patients.

PMID- 26207650
TI  - Decreased pain sensitivity among people with schizophrenia: a meta-analysis of
      experimental pain induction studies.
AB  - Patients with schizophrenia report reduced pain sensitivity in clinical studies,
      but experimental studies are required to establish pain sensitivity as a
      potential endophenotype. We conducted a systematic review of electronic databases
      from database inception until April 15, 2015, including experimental studies
      investigating pain among patients with schizophrenia spectrum disorder vs healthy
      controls. A random-effect meta-analysis yielding Hedges' g +/-95% confidence
      intervals (CIs) as the effect size (ES) measure was conducted. Primary outcome
      was a pooled composite of pain threshold and pain tolerance; secondary outcomes
      included these parameters individually, plus sensory threshold, physiological
      pain response, and pain intensity or unpleasantness. Across 17 studies, patients
      with schizophrenia spectrum disorder (n = 387; age, 30.7 +/- 6.9 years; females,
      31.9%; illness duration, 7.0 +/- 5.7 years) were compared with controls (n = 483;
      age, 29.5 +/- 7.4 years; females, 31.0%). Patients had elevated pain
      threshold/pain tolerance vs controls (ES = 0.583; 95% CI, 0.212-0.954; P = 0.002;
      studies = 15). Results were similar in antipsychotic-free individuals (ES =
      0.599; 95% CI, 0.291-0.907; P < 0.0001; studies = 8), with trend-level
      significance in antipsychotic-treated individuals (ES = 0.566; 95% CI, -0.007 to
      1.125; P = 0.047; studies = 9). Likewise, patients with schizophrenia had
      increased pain tolerance (ES = 0.566; 95% CI, 0.235-0.897; P = 0.0001; studies =
      6), sensory threshold (ES = 1.16; 95% CI, 0.505-1.727; P < 0.0001; studies = 5),
      and pain threshold (ES = 0.696; 95% CI, 0.407-0.986; P < 0.001; studies = 9), as
      well as reduced physiological response to noxious stimuli (ES = 0.456; 95% CI,
      0.131-0.783; P = 0.006) and pain intensity/unpleasantness ratings (ES = 0.547;
      95% CI, 0.146-0.949; P = 0.008). Findings were similarly significant in
      antipsychotic-free patients with schizophrenia (analysable parameters = 4) and
      antipsychotic-treated individuals (analysable parameters = 2). Finally, greater
      psychiatric symptoms moderated increased pain threshold, and younger patient age
      moderated increased pain tolerance. Decreased pain sensitivity seems to be an
      endophenotype of schizophrenia spectrum disorders. How this alteration links to
      other dimensions of schizophrenia and physical comorbidity-related help-seeking
      behaviour/morbidity/mortality requires further study. 

PMID- 26207651
TI  - Systematic review of the Face, Legs, Activity, Cry and Consolability scale for
      assessing pain in infants and children: is it reliable, valid, and feasible for
      use?
AB  - The Face, Legs, Activity, Cry and Consolability (FLACC) scale is one of the most
      widely used behavioural observation pain scales. However, the psychometrics of
      the scale have not been adequately summarised and evaluated to provide clear
      recommendations regarding its use. The aim of this study was to rigorously
      evaluate the reliability, validity, feasibility, and utility of the scale for
      clinical and research purposes and provide recommendations regarding appropriate
      use of the scale. Databases searched were MEDLINE, CINAHL, Embase, PsycINFO
      (using the Ovid, PubMed, and Ebscohost platforms), The Cochrane Database of
      Systematic reviews and Cochrane Controlled Trials, and Google Scholar.
      Psychometric evaluation studies reporting feasibility, reliability, validity, or
      utility data for the FLACC scale applied to children (birth to 18 years) and
      randomised controlled trials (RCT) using the FLACC scale to measure a study
      outcome in infants and children. Data extraction included study design,
      population demographics, and psychometric data. Analysis involved in this study
      are quality assessment of the psychometric evaluation studies and the RCTs using
      the COSMIN checklist and the Jadad scale, respectively, and narrative synthesis
      of all results. Twenty-five psychometric evaluations studies and 52 RCTs were
      included. The study population, circumstances, and quality of the studies varied
      greatly. Sufficient data addressing postoperative pain assessment in infants and
      children exist. Some positive data support the psychometrics of the scale used to
      assess postoperative pain in children with cognitive impairment. Limited and
      conflicting data addressing procedural pain assessment exist. Content validity
      and scale feasibility have had limited psychometric evaluation. There are
      insufficient data to support the FLACC scale for use in all circumstances and
      populations to which is currently applied. 

PMID- 26207649
TI  - COMT gene locus: new functional variants.
AB  - Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic
      neurotransmitters. Numerous studies have linked COMT to pivotal brain functions
      such as mood, cognition, response to stress, and pain. Both nociception and risk
      of clinical pain have been associated with COMT genetic variants, and this
      association was shown to be mediated through adrenergic pathways. Here, we show
      that association studies between COMT polymorphic markers and pain phenotypes in
      2 independent cohorts identified a functional marker, rs165774, situated in the
      3' untranslated region of a newfound splice variant, (a)-COMT. Sequence
      comparisons showed that the (a)-COMT transcript is highly conserved in primates,
      and deep sequencing data demonstrated that (a)-COMT is expressed across several
      human tissues, including the brain. In silico analyses showed that the (a)-COMT
      enzyme features a distinct C-terminus structure, capable of stabilizing
      substrates in its active site. In vitro experiments demonstrated not only that
      (a)-COMT is catalytically active but also that it displays unique substrate
      specificity, exhibiting enzymatic activity with dopamine but not epinephrine.
      They also established that the pain-protective A allele of rs165774 coincides
      with lower COMT activity, suggesting contribution to decreased pain sensitivity
      through increased dopaminergic rather than decreased adrenergic tone,
      characteristic of reference isoforms. Our results provide evidence for an
      essential role of the (a)-COMT isoform in nociceptive signaling and suggest that
      genetic variations in (a)-COMT isoforms may contribute to individual variability
      in pain phenotypes. 

PMID- 26207652
TI  - Is regular systemic opioid analgesia associated with shorter survival in adult
      patients with cancer? A systematic literature review.
AB  - Opioids are important in the management of pain in patients with cancer.
      Clinicians and patients are sometimes concerned about the effect of opioids on
      survival, which might decrease opioid prescription, compliance, and symptom
      control. We wanted to determine whether opioid analgesia was associated with
      shorter survival in adult patients with cancer. We systematically searched for
      studies that assessed the effect of regular systemic opioid analgesia on
      survival. We identified 526 unique records, with 20 articles meeting inclusion
      criteria. Thirteen end-of-life studies, including 11 very low-quality
      retrospective studies, did not find a consistent association between opioid
      analgesic treatment and survival; this evidence comes from low-quality studies,
      so should be interpreted with caution. Seven longer-term studies, including three
      randomised controlled trials and two prospective studies, were included. Six of
      these studies indicated that opioids were likely to be associated with a shorter
      survival. None of these studies were powered to assess the effect of opioids on
      survival as a primary endpoint. In view of this, no definitive conclusions can be
      made as to whether opioids affect survival in patients with cancer. These data
      suggest that while opioid analgesia does not affect survival at the end of life,
      in the context of longer-term treatment, higher-quality studies, with survival as
      a primary endpoint, are needed to confirm an independent association between
      opioid analgesia and shorter survival. An important limitation of research in
      this field is that the relationship between greater analgesic requirements and
      shorter survival may be mediated by painful progressive cancer. 

PMID- 26207653
TI  - Iron-catalyzed direct alpha-arylation of ethers with azoles.
AB  - The direct alpha-arylation of cyclic and acyclic ethers with azoles has been
      achieved, which features a novel iron-catalyzed cross-dehydrogenative coupling
      (CDC) process. This practical oxidative method allowed the efficient C2
      alkylation of a variety of (benzo)azoles constituting straightforward access to
      heterocycles of utmost medicinal significance and highlighting the convenient use
      of feedstock substrates and iron catalysts. A preliminary mechanism supported by
      DFT calculations is discussed as well. 

PMID- 26207654
TI  - Hospital employment of physicians and supply chain performance: An empirical
      investigation.
AB  - BACKGROUND: As hospital employment of physicians becomes increasingly common in
      the United States, much speculation exists as to whether this type of arrangement
      will promote hospital operating efficiency in such areas as supply chain
      management. Little empirical research has been conducted to address this
      question. PURPOSE: The aim of this study was to provide an exploratory assessment
      of whether hospital employment of physicians is associated with better supply
      chain performance. Drawing from both agency and stewardship theories, we examined
      whether hospitals with a higher proportion of employed medical staff members have
      relatively better supply chain performance based on two performance measures,
      supply chain expenses and inventory costs. APPROACH: We conducted the study using
      a pooled, cross-sectional sample of hospitals located in California between 2007
      and 2009. Key data sources were hospital annual financial reports from
      California's Office of Statewide Health Policy and Development and the American
      Hospital Association annual survey of hospitals. To examine the relationship
      between physician employment and supply chain performance, we specified physician
      employment as the proportion of total employed medical staff members as well as
      the proportion of employed medical staff members within key physician subgroups.
      We analyzed the data using generalized estimating equations. FINDINGS: Study
      results generally supported our hypothesis that hospital employment of physicians
      is associated with better supply chain performance. PRACTICAL IMPLICATIONS:
      Although the results of our study should be viewed as preliminary, the trend in
      the United States toward hospital employment of physicians may be a positive
      development for improved hospital operating efficiency. Hospital managers should
      also be attentive to training and educational resources that medical staff
      members may need to strengthen their role in supply chain activities.

PMID- 26207656
TI  - Synthesis and luminescence properties of a novel red-emitting LiSr4(BN2)3:Eu(2+)
      phosphor.
AB  - A near-UV excited phosphor, LiSr4(BN2)3:Eu(2+) (LSBN:Eu(2+)), was synthesized
      using a solid-state reaction at 800  degrees C. The crystal structure of LSBN had
      been refined and determined from the XRD profiles by the Rietveld refinement
      method, which belongs to the space group Im3[combining macron]m with the lattice
      constants a = b = c = 7.46112(23) A. The excitation spectra of the LSBN:Eu(2+)
      phosphors were centered at around 370 nm and covered the range from 300 to 450
      nm. Under 400 nm excitation, the emission spectra of the LSBN:Eu(2+) phosphors
      show a red emission centered at about 640 nm (FWHM ~ 130 nm). And the energy
      transfer between the Eu(2+) ions is confirmed to arise from the electric dipole
      dipole interactions. The nontypical emission blue-shift in the single
      luminescence center with increasing temperature luminescence properties is also
      investigated. The results indicate that LSBN:Eu(2+) could be conducive to the
      development of white light emitting diodes. 

PMID- 26207655
TI  - Improve employee engagement to retain your workforce.
AB  - BACKGROUND: Turnover hurts patient care quality and is expensive to hospitals.
      Improved employee engagement could encourage employees to stay at their
      organization. PURPOSE: The aim of the study was to test whether participants in
      an employee engagement program were less likely than nonparticipants to leave
      their job. METHODS: Health care workers (primarily patient care technicians and
      assistants, n = 216) were recruited to participate in an engagement program that
      helps employees find meaning and connection in their work. Using human resources
      data, we created a longitudinal study to compare participating versus
      nonparticipating employees in the same job titles on retention time (i.e.,
      termination risk). FINDINGS: Participants were less likely to leave the hospital
      compared to nonparticipating employees (hazard ratio = 0.22, 95% CI [0.11,
      0.84]). This finding remained significant after adjusting for covariates (hazard
      ratio = 0.37, 95% CI [0.17, 0.57]). PRACTICE IMPLICATIONS: Improving employee
      engagement resulted in employees staying longer at the hospital.

PMID- 26207657
TI  - Introduction to the L'Oreal supplement.

PMID- 26207658
TI  - Skin lightening practices: an epidemiological study of South African women of
      African and Indian ancestries.
AB  - BACKGROUND: Cutaneous adverse sequelae of skin lightening creams present with
      myriad skin complications and affect dermatology practice, particularly in sub
      Saharan Africa where such products are widely used, with a prevalence of 25-67%.
      OBJECTIVES: To examine the skin lightening practices of both African and Indian
      women living in South Africa. METHODS: A cross-sectional survey was undertaken in
      the general outpatient departments of two regional university hospitals in
      Durban, South Africa. All consenting African and Indian women aged 18-70 years
      were recruited and asked to complete a questionnaire. RESULTS: Six hundred women
      completed the questionnaire, of whom 32.7% reported using skin lightening
      products. The main reasons cited were treatment of skin problems (66.7%) and skin
      lightening (33.3%). Products were purchased from a variety of sources. Twenty
      five percent reported using sunscreen. CONCLUSIONS: The use of skin lightening
      cosmetics is common among darkly pigmented South African women, including those
      of both African and Indian ancestries. Despite more than 20 years of governmental
      regulations aimed at prohibiting both the sale of cosmetics containing mercury,
      hydroquinone and corticosteroids, and the advertising of any kind of skin
      lightener, they are far from having disappeared. The main motivations for using
      these products are the desire to treat skin disorders and to achieve a lighter
      skin colour. Television and magazine advertisements seem to influence women's
      choice of these products and, thus, would be efficient channels for raising
      public awareness about the dangers of using uncontrolled skin lighteners.

PMID- 26207659
TI  - Understanding breakage in curly hair.
AB  - BACKGROUND: In 2005, the L'Oreal Institute for hair and skin research carried out
      a multiethnic study to investigate hair breakage in women residing in the U.S.A.
      In this study it was reported that a large percentage (96%) of the African
      American respondents experience breakage. A combination of structural differences
      and grooming-induced stresses seem to contribute to the higher breakage incidence
      in the African-American group as the chemical composition of African-American
      hair is not significantly different from other ethnic groups. Some authors have
      proposed that the repeated elongation, torsion and flexion actions may affect the
      components of the hair fibre. However, considering the different properties of
      cuticle and cortex, one would expect a different wearing mechanism of each,
      leading to the ultimate failure of hair. Knowing in detail how each part of the
      structure fails can potentially lead to better ways to protect the hair from
      physical insults. OBJECTIVE: To investigate crack propagation and fracture
      mechanisms in African-American hair. METHODS: Virgin hair of excellent quality
      was collected, with informed consent, from a female African-American volunteer. A
      series of controlled mechanical stresses was applied to 10-mm hair sections using
      a high-resolution mechanical stage (20 mN) up to the fracture of the fibre. The
      surface was monitored using scanning electron microscopy imaging during the
      stress application. X-ray tomographic microscopy images were acquired and
      quantified to detect changes in energy absorption as a function of applied stress
      that could be linked to increase in crack density. RESULTS: Analysis of the
      mechanical response of hair combined with the two imaging techniques led us to
      propose the following mechanism of hair breakage: cuticle sliding; failure of the
      cuticle-cortex interface; nucleation of intercellular cracks and growth of cracks
      at the cuticle-cortex junction; and propagation of intercellular cracks towards
      the surface of the hair and final breakage when these cracks merge at the
      cuticular junction. CONCLUSIONS: The combination of scanning electron microscopy
      and X-ray tomography provided new information about the fracture of hair.
      Mechanical damage from grooming and some environmental factors accumulate in hair
      creating internal cracks that eventually result in breakage at unpredictable
      sites and therefore a continuous care regimen for the hair throughout the life
      cycle of the fibres is recommended.

PMID- 26207660
TI  - Skin cancer: an African perspective.
AB  - The objective of this review article is to assess skin cancer and sun protection
      trends in darker-skinned Africans. The published information suggests that in
      order to reduce the skin cancer mortality rate amongst people of colour, a
      broader effort towards public awareness/education is necessary. 

PMID- 26207661
TI  - Perceived aetiological factors of folliculitis keloidalis nuchae (acne
      keloidalis) and treatment options among Nigerian men.
AB  - BACKGROUND: Folliculitis keloidalis nuchae (FKN) also known as acne keloidalis is
      the commonest form of scarring alopecia occurring in African males. It occurs
      mostly in individuals of African descent. Its prevalence ranges from 1.6% to
      16.1%. FKN is multifactorial in origin: androgens, inflammation, trauma,
      ingrowing hairs and secondary infection have all been implicated in its
      aetiology. The reason for its occurrence in the occipital region is unclear
      although elevated androgens in the scalp have been suggested. The occurrence of
      huge keloidal-like scars in the affected area has earned the name 'Bumps' in this
      environment. OBJECTIVES: To look at the community's perception of the
      aetiological factors for bumps and perceived management options available in our
      environment. METHODS: A community study was carried out among 1003 men residing
      in an urban community in Mokola, Ibadan, Oyo State, Nigeria. Data on
      sociodemographic characteristics, knowledge about aetiology, and prevalence of
      shaving bumps was obtained using a semi-structured questionnaire administered by
      trained interviewers. The chi-squared test was used to test the associations
      between presence of FKN and variables. RESULTS: The mean age of the respondents
      was 31.6 (SD = 8) years. When asked about the cause of shaving bumps, 420 (41.9%)
      felt it was due to infection from barber's instruments, followed by heredity
      (110, 11%), poor shaving technique (81, 8.1%), cuts from shaving (52, 5.2%) and
      inadequate after shaving care (39, 3.9%). The prevalence of shaving bumps was
      2.7%. The most commonly reported symptom among those with shaving bumps was
      itching (71.1%). Other symptoms include pain (9.6%) and bleeding (1.2%). Most of
      the patients (70.8%) who had ever had shaving bumps practised self-medication.
      Medications applied included oral and topical antibiotics (20.3%), Neo-medrol
      (10.9%), engine oil (9.4%) and traditional leaves (9.4%). CONCLUSIONS: About 50%
      of the responders believed FKN was an infective disorder. Although bleeding
      occurred while having a haircut, some individuals did not have their own personal
      shaving kits. Antibiotics, topical steroids, herbs and caustic substances were
      used for treatment. There is an urgent need to stimulate safer hair shaving
      practices and discourage the wrong treatment of FKN.

PMID- 26207662
TI  - Negative cutaneous effects of medicinal plants in Senegal.
AB  - Use of medicinal plants is common and widespread throughout Africa, including in
      Senegal. Because efficacy has been demonstrated, public policies have been
      instituted that have allowed plant-based therapies to have an important role in
      general primary care. However, little is known about the cutaneous safety of many
      plant-based therapies. In this 6-month prospective study all cases of dermatitis
      induced or aggravated by exclusive use of medicinal plants were evaluated via
      skin allergy testing. The results were classified and compared with the available
      literature. Forty-three cases of plant-therapy-associated cutaneous reactions
      were identified, including worsening of existing conditions (56%), recurrence of
      a previously resolved condition (16%) and new dermatitis arising spontaneously
      (28%). In the cases where the condition was new, generalized exfoliative
      dermatitis occurred in 42% of cases with an average time of onset of 9 days.
      Specific plants were identified in 65% of cases and included 18 varieties. The
      frequency and severity of plant-induced cutaneous reactions should be the basis
      for the creation of a phytovigilance programme and re-evaluation of how
      traditional medicine is used in the general population. When irritation occurs,
      identification of the responsible plant and allergy testing should be the first
      steps towards relieving symptoms. 

PMID- 26207663
TI  - Erratum: A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila.
AB  - An author's name was corrected in the publication of A Method to Inflict Closed
      Head Traumatic Brain Injury in Drosophila. The second to last author's was
      spelled incorrectly. It has been updated from: Barry Ganetky to: Barry Ganetzky. 

PMID- 26207664
TI  - Letter to the Editor: Hemorrhagic infarction following open fenestration of
      intracranial arachnoid cyst.

PMID- 26207665
TI  - Management of idiopathic pediatric syringohydromyelia.
AB  - OBJECT: Syringohydromyelia is frequently identified on spinal imaging. The
      literature provides little guidance to decision making regarding the need for
      follow-up or treatment. The purpose of this study was to review the authors'
      experience in managing pediatric syringohydromyelia of unknown cause. METHODS: A
      single-institution retrospective review of all cases involving pediatric patients
      who underwent spinal MRI from 2002 to 2012 was conducted. Patients with
      idiopathic syringohydromyelia (IS) were identified and categorized into 2
      subgroups: uncomplicated idiopathic syrinx and IS associated with scoliosis.
      Clinical and radiological course were analyzed. RESULTS: Ninety-eight patients
      (50 female, 48 male) met the inclusion criteria. Median age at diagnosis of
      syrinx was 11.9 years. Median maximum syrinx size was 2 mm (range 0.5-17 mm) and
      spanned 5 vertebral levels (range 1-20 vertebral levels). Thirty-seven patients
      had scoliosis. The most common presenting complaint was back pain (26%). Clinical
      follow-up was available for 78 patients (80%), with a median follow-up of 20.5
      months (range 1-143 months). A neurological deficit existed at presentation in
      36% of the patients; this was either stable or improved at last follow-up in 64%
      of cases. Radiological follow-up was available for 38 patients (39%), with a
      median duration of 13 months (range 2-83 months). There was no change in syrinx
      size in 76% of patients, while 16% had a decrease and 8% had an increase in
      syrinx size. Thirty-six patients had both clinical and radiological follow-up.
      There was concordance between clinical and radiological course in 14 patients
      (39%), with 11 patients (31%) showing no change and 3 patients (8%) showing
      clinical and radiological improvement. No patients had concurrent deterioration
      in clinical and radiological course. One patient with scoliosis and muscular
      dystrophy underwent direct surgical treatment of the syrinx and subsequently had
      a deteriorated clinical course and decreased syrinx size. CONCLUSIONS: There
      remains a paucity of data regarding the management of pediatric IS. IS in
      association with scoliosis can complicate neurosurgical decision making. There
      was no concordance between radiological syrinx size increase and clinical
      deterioration in this cohort, indicating that surgical decision making should
      reflect clinical course as opposed to radiological course.

PMID- 26207666
TI  - Descending transtentorial herniation, a rare complication of the treatment of
      trapped fourth ventricle: case report.
AB  - Descending transtentorial herniation (DTH) is a complication of raised pressure
      in the supratentorial compartment, usually resulting from mass lesion of several
      etiologies. The authors report an exceptional case of DTH complicating the
      implant of a CSF shunting device in the trapped fourth ventricle of a 17-year-old
      boy in whom a second CSF shunting device had been implanted for neonatal
      posthemorrhagic and postinfectious hydrocephalus. The insidious clinical and
      radiological presentation of DTH, mimicking a malfunction of the supratentorial
      shunt, is documented. Ultimately, the treatment consisted of removal of the
      infratentorial shunt and endoscopic acqueductoplasty with stenting. The absence
      of supratentorial mass lesion and other described etiologies of DTH prompted the
      authors to speculate on the hydrodynamic pathogenesis of DTH in the present case.

PMID- 26207667
TI  - Long-term developmental follow-up in children with nonsyndromic craniosynostosis.
AB  - OBJECT: The aim of this study was to determine the distribution of Full Scale IQ
      (FSIQ) by type of craniosynostosis and to verify the finding that at long-term
      follow-up, verbal IQ (VIQ) is significantly higher than performance IQ (PIQ) in
      patients with single-suture sagittal synostosis (SS) despite falling within the
      "average" range for intelligence. Whether this also occurs in other types of
      craniosynostosis and whether surgery and sex are relevant were also determined.
      The relationship between age at time of surgery and later IQ was ascertained.
      METHODS: The data for 91 children with craniosynostosis (47 sagittal, 15
      unicoronal, 13 metopic, 9 multisuture, and 7 bicoronal) were collected at their
      routine, 10 years of age IQ assessment (mean age 123.8 months). The patients
      included 61 males and 30 females; 62 patients had undergone surgery and 29 had
      not. RESULTS: The mean FSIQ for all types of craniosynostosis combined (96.2)
      fell within the average range for the general population. Some variation was
      evident across the different types of craniosynostosis: the SS group showed the
      highest FSIQs and a "normal" distribution of bandings; the other types had a
      higher proportion of FSIQs in the lower bandings. The data confirmed the finding
      that VIQ is greater than PIQ despite falling within the average range for
      intelligence, with a difference of 5.0 for all types of craniosynostosis combined
      (p = 0.001), 7.6 for the SS group (p = 0.001), and 6.9 for the unicoronal group
      (p = 0.029). This VIQ > PIQ effect was not found with multisuture
      craniosynostosis. The VIQ > PIQ discrepancy occurred regardless of whether the
      patient had undergone surgery and occurred more often in males than females. In
      the SS group and the bicoronal group, FSIQ (p = 0.036 and p = 0.046,
      respectively) and PIQ (p = 0.012 and p = 0.017, respectively), though not VIQ,
      were higher when surgery had been performed early. CONCLUSIONS: The study
      confirms that at long-term follow-up, although children with nonsyndromic
      craniosynostosis fall within the normal range for intelligence, there is a VIQ >
      PIQ discrepancy above what would be expected in the normal population, which may
      be indicative of more subtle difficulties in achievement. This discrepancy is
      affected by type of craniosynostosis, sex, and age at time of surgery.

PMID- 26207668
TI  - Feasibility of CT-based intraoperative 3D stereotactic image-guided navigation in
      the upper cervical spine of children 10 years of age or younger: initial
      experience.
AB  - OBJECT Rigid screw fixation may be technically difficult in the upper cervical
      spine of young children. Intraoperative stereotactic navigation may potentially
      assist a surgeon in precise placement of screws in anatomically challenging
      locations. Navigation may also assist in defining abnormal anatomy. The object of
      this study was to evaluate the authors' initial experience with the feasibility
      and accuracy of this technique, both for resection and for screw placement in the
      upper cervical spine in younger children. METHODS Eight consecutive pediatric
      patients 10 years of age or younger underwent upper cervical spine surgery aided
      by image-guided navigation. The demographic, surgical, and clinical data were
      recorded. Screw position was evaluated with either an intraoperative or
      immediately postoperative CT scan. RESULTS One patient underwent navigation
      purely for guidance of bony resection. A total of 14 navigated screws were placed
      in the other 7 patients, including 5 C-2 pedicle screws. All 14 screws were
      properly positioned, defined as the screw completely contained within the
      cortical bone in the expected trajectory. There were no immediate complications
      associated with navigation. CONCLUSIONS Image-guided navigation is feasible
      within the pediatric cervical spine and may be a useful surgical tool for placing
      screws in a patient with small, often difficult bony anatomy. The authors
      describe their experience with their first 8 pediatric patients who underwent
      navigation in cervical spine surgery. The authors highlight differences in
      technique compared with similar navigation in adults.

PMID- 26207669
TI  - Letter to the Editor: Arachnoid cyst and the hemorrhagic complications of open
      decompression.

PMID- 26207670
TI  - Hand anthropometry survey of rural farm workers in south-eastern Nigeria.
AB  - The importance of hand anthropometry as it relates to design of hand tools
      particularly for farm workers have been established; however, anthropometric data
      for this group of agricultural workers have continued to remain scarce. A survey
      of hand anthropometry relevant in design of agricultural hand tools was carried
      out on 200 male and 100 female adult farm workers in south-eastern Nigeria.
      Comparison of the male and female data obtained showed that male dimensions were
      higher than that recorded for the females. The hand anthropometric data of the
      male and female farm workers were compared with that of other populations but no
      clear distinction was observed. It was however clear that the following hand
      dimensions, 2nd Joint to root digit 3 and width at tip digit 3 recorded for
      Nigerian farm workers were highest and lowest, respectively, compared to other
      populations. Practitioner Summary: Hand anthropometric data relevant in design of
      hand tools have continued to remain scarce particularly for farm workers. Hand
      anthropometry survey of farm workers carried out in south-eastern Nigeria
      revealed higher dimensions for males than females; however, no clear distinction
      was observed in comparison with other populations. 

PMID- 26207672
TI  - Measurement of various respiratory dynamics parameters following acute
      inhalational exposure to soman vapor in conscious rats.
AB  - Respiratory dynamics were investigated in head-out plethysmography chambers
      following inhalational exposure to soman in untreated, non-anesthetized rats. A
      multipass saturator cell was used to generate 520, 560 and 600 mg * min/m(3) of
      soman vapor in a customized inhalational exposure system. Various respiratory
      dynamic parameters were collected from male Sprague-Dawley rats (300--350 g)
      during (20 min) and 24 h (10 min) after inhalational exposure. Signs of CWNA
      induced cholinergic crisis were observed in all soman-exposed animals. Percentage
      body weight loss and lung edema were observed in all soman-exposed animals, with
      significant increases in both at 24 h following exposure to 600 mg * min/m(3).
      Exposure to soman resulted in increases in respiratory frequency (RF) in animals
      exposed to 560 and 600 mg * min/m(3) with significant increases following
      exposure to 560 mg * min/m(3) at 24 h. No significant alterations in inspiratory
      time (IT) or expiratory time (ET) were observed in soman-exposed animals 24 h
      post-exposure. Prominent increases in tidal volume (TV) and minute volume (MV)
      were observed at 24 h post-exposure in animals exposed to 600 mg * min/m(3). Peak
      inspiratory (PIF) and expiratory flow (PEF) followed similar patterns and
      increased 24 h post-exposure to 600 mg * min/m(3) of soman. Results demonstrate
      that inhalational exposure to 600 mg * min/m(3) soman produces notable
      alterations in various respiratory dynamic parameters at 24 h. The following
      multitude of physiological changes in respiratory dynamics highlights the need to
      develop countermeasures that protect against respiratory toxicity and lung
      injury.

PMID- 26207671
TI  - Snail promotes cell migration through PI3K/AKT-dependent Rac1 activation as well
      as PI3K/AKT-independent pathways during prostate cancer progression.
AB  - Snail, a zinc-finger transcription factor, induces epithelial-mesenchymal
      transition (EMT), which is associated with increased cell migration and
      metastasis in cancer cells. Rac1 is a small G-protein which upon activation
      results in formation of lamellipodia, the first protrusions formed by migrating
      cells. We have previously shown that Snail promotes cell migration through down
      regulation of maspin tumor suppressor. We hypothesized that Snail's regulation of
      cell migration may also involve Rac1 signaling regulated by PI3K/AKT and/or MAPK
      pathways. We found that Snail overexpression in LNCaP and 22Rv1 prostate cancer
      cells increased Rac1 activity associated with increased cell migration, and the
      Rac1 inhibitor, NSC23766, could inhibit Snail-mediated cell migration.
      Conversely, Snail downregulation using shRNA in the aggressive C4-2 prostate
      cancer cells decreased Rac1 activity and cell migration. Moreover, Snail
      overexpression increased ERK and PI3K/AKT activity in 22Rv1 prostate cancer
      cells. Treatment of Snail-overexpressing 22Rv1 cells with LY294002, PI3K/AKT
      inhibitor or U0126, MEK inhibitor, decreased cell migration significantly, but
      only LY294002 significantly reduced Rac1 activity, suggesting that Snail promotes
      Rac1 activation via the PI3K/AKT pathway. Furthermore, 22Rv1 cells overexpressing
      Snail displayed decreased maspin levels, while inhibition of maspin expression in
      22Rv1 cells with siRNA, led to increased PI3K/AKT, Rac1 activity and cell
      migration, without affecting ERK activity, suggesting that maspin is upstream of
      PI3K/AKT. Overall, we have dissected signaling pathways by which Snail may
      promote cell migration through MAPK signaling or alternatively through PI3K/AKT
      Rac1 signaling that involves Snail inhibition of maspin tumor suppressor. This
      may contribute to prostate cancer progression.

PMID- 26207673
TI  - The impact of practical support on parental bereavement: Reflections from a study
      involving parents bereaved through military death.
AB  - This article, drawing on data from a wider study, describes the impact that U.K.
      bereaved military parents ascribe to the practical support (help with home and
      garden maintenance) that they received following the death of their son. The type
      of practical support offered to parents has had a wide-ranging and significant
      impact on them. In addition to helping them find meaning and maintain continuing
      bonds, this form of support contributed to their capacity to engage in
      restoration-focused coping. As a symbolic resource, this type of practical
      support may be a significant moderator of distress in the psychosocial transition
      of bereavement. 

PMID- 26207674
TI  - Chemical Characterization of Urate Hydroperoxide, A Pro-oxidant Intermediate
      Generated by Urate Oxidation in Inflammatory and Photoinduced Processes.
AB  - Urate hydroperoxide is a strong oxidant generated by the combination of urate
      free radical and superoxide. The formation of urate hydroperoxide as an
      intermediate in urate oxidation is potentially responsible for the pro-oxidant
      effects of urate in inflammatory disorders, protein degradation, and food
      decomposition. To understand the molecular mechanisms that sustain the harmful
      effects of urate in inflammatory and oxidative stress related conditions, we
      report a detailed structural characterization and reactivity of urate
      hydroperoxide toward biomolecules. Urate hydroperoxide was synthesized by photo
      oxidation and by a myeloperoxidase/hydrogen peroxide/superoxide system. Multiple
      reaction monitoring (MRM) and MS(3) ion fragmentation revealed that urate
      hydroperoxide from both sources has the same chemical structure. Urate
      hydroperoxide has a maximum absorption at 308 nm, epsilon308nm = 6.54 +/- 0.38 *
      10(3) M(-1) cm(-1). This peroxide decays spontaneously with a rate constant of k
      = 2.80 +/- 0.18 * 10(-4) s(-1) and a half-life of 41 min at 22  degrees C. Urate
      hydroperoxide undergoes electrochemical reduction at potential values less
      negative than -0.5 V (versus Ag/AgCl). When incubated with taurine, histidine,
      tryptophan, lysine, methionine, cysteine, or glutathione, urate hydroperoxide
      reacted only with methionine, cysteine, and glutathione. The oxidation of these
      molecules occurred by a two-electron mechanism, generating the alcohol,
      hydroxyisourate. No adduct between cysteine or glutathione and urate
      hydroperoxide was detected. The second-order rate constant for the oxidation of
      glutathione by urate hydroperoxide was 13.7 +/- 0.8 M(-1) s(-1). In conclusion,
      the oxidation of sulfur-containing biomolecules by urate hydroperoxide is likely
      to be a mechanism by which the pro-oxidant and damaging effects of urate are
      mediated in inflammatory and photo-oxidizing processes. 

PMID- 26207676
TI  - ?

PMID- 26207675
TI  - Portable hyperspectral imager with continuous wave green laser for identification
      and detection of untreated latent fingerprints on walls.
AB  - Untreated latent fingerprints are known to exhibit fluorescence under UV laser
      excitation. Previously, the hyperspectral imager (HSI) has been primarily
      evaluated in terms of its potential to enhance the sensitivity of latent
      fingerprint detection following treatment by conventional chemical methods in the
      forensic science field. In this study however, the potential usability of the HSI
      for the visualization and detection of untreated latent fingerprints by measuring
      their inherent fluorescence under continuous wave (CW) visible laser excitation
      was examined. Its potential to undertake spectral separation of overlapped
      fingerprints was also evaluated. The excitation wavelength dependence of
      fluorescent images was examined using an untreated palm print on a steel based
      wall, and it was found that green laser excitation is superior to blue and yellow
      lasers' excitation for the production of high contrast fluorescence images. In
      addition, a spectral separation method for overlapped fingerprints/palm prints on
      a plaster wall was proposed using new images converted by the division and
      subtraction of two single wavelength images constructed based on measured
      hyperspectral data (HSD). In practical tests, the relative isolation of two
      overlapped fingerprints/palm prints was successful in twelve out of seventeen
      cases. Only one fingerprint/palm print was extracted for an additional three
      cases. These results revealed that the feasibility of overlapped fingerprint/palm
      print spectral separation depends on the difference in the temporal degeneration
      of each fluorescence spectrum. The present results demonstrate that a combination
      of a portable HSI and CW green laser has considerable potential for the
      identification and detection of untreated latent fingerprints/palm prints on the
      walls under study, while the use of HSD makes it practically possible for doubly
      overlapped fingerprints/palm prints to be separated spectrally. 

PMID- 26207678
TI  - ?

PMID- 26207677
TI  - ?

PMID- 26207679
TI  - ?

PMID- 26207680
TI  - Enhanced Human Decidual Cell-Expressed FKBP51 May Promote Labor-Related
      Functional Progesterone Withdrawal.
AB  - Sustained plasma progesterone (P4) levels suggest initiation of human term labor
      by functional P4 withdrawal, reflecting reduced progesterone receptor (PR) and/or
      glucocorticoid receptor (GR) expression or activity. The steroid-induced
      immunophilin cochaperone FKBP51 inhibits PR- and GR-mediated transcription,
      suggesting a labor-initiating role. Gestational age-matched decidual sections
      were immunostained for FKBP51 and decidual cell (DC) and interstitial trophoblast
      (IT) markers, vimentin and cytokeratin, respectively. Term DC cultures were
      incubated with vehicle (control), estradiol (E2) with or without
      medroxyprogesterone acetate, dexamethasone (Dex), or Organon 2058. FKBP51
      histologic scoring was significantly higher in DC nuclei during labor versus
      prelabor decidua, whereas FKBP51 immunostaining was undetected in interstitial
      trophoblasts (P < 0.05). In term DC cultures, E2 + medroxyprogesterone acetate or
      E2 + Dex enhanced FKBP51 expression (P < 0.01), whereas E2 + Organon 2058
      inhibited PR expression (P < 0.05), and E2 + Dex inhibited GR expression (P <
      0.05). Unlike term DCs, FKBP51 was undetected in control or Dex-treated cultured
      third-trimester trophoblasts. Electrophoretic mobility shift assays revealed that
      FKPB51 overexpression or silencing in cultured DCs altered PR-DNA binding.
      Increased FKBP51 levels in term DCs during labor complement our prior in situ
      observations of significantly lower PR in labor versus prelabor DCs. In a milieu
      of sustained plasma P4 levels, these reciprocal changes will amplify functional
      P4 withdrawal in DCs via FKBP51-mediated PR resistance coupled with declining PR
      levels, whereas the lack of FKBP51 expression in interstitial trophoblasts
      suggests unopposed constitutive GR action.

PMID- 26207681
TI  - Metabolic interactions in microbial communities: untangling the Gordian knot.
AB  - Metabolic exchanges are ubiquitous in microbial communities. However, detecting
      metabolite cross-feedings is difficult due to their intrinsically dynamic nature
      and the complexity of communities. Thus, while exhaustive description of
      metabolic networks operating in natural systems is a task for the future, the
      battle of today is divided between detailed characterizations of small, reduced
      complexity microbial consortia, and focusing on particular metabolic aspects of
      natural ecosystems. Detecting metabolic interactions requires methodological
      blend able to capture species identity, dependencies and the nature of exchanged
      metabolites. Multiple combinations of diverse techniques, from metagenomics to
      imaging mass spectrometry, offer solutions to this challenge, each combination
      being tailored to the community at hand. 

PMID- 26207682
TI  - A Mouse Ear Model for Bystander Studies Induced by Microbeam Irradiation.
AB  - Radiation-induced bystander effects have been observed in vitro and in cell and
      tissue culture models, however, there are few reported studies showing these
      effects in vivo. To our knowledge, this is the first reported study on bystander
      effects induced by microbeam irradiation in an intact living mammal. The mouse
      ear was used to investigate radiation-induced bystander effects in keratinocytes,
      utilizing a 3 MeV proton microbeam (LET 13.1 keV/MUm) with a range in skin of
      about 135 MUm. Using a custom-designed holder, the ear of an anesthetized
      C57BL/6J mouse was flattened by gentle suction and placed over the microbeam port
      to irradiate cells along a 35 MUm wide, 6 mm long path. Immunohistochemical
      analysis of gamma-H2AX foci formation in tissue sections revealed, compared to
      control tissue, proton-induced gamma-H2AX foci formation in one of the two
      epidermal layers of the mouse ear. Strikingly, a higher number of cells than
      expected showed foci from direct irradiation effects. Although the proton
      irradiated line was ~35 MUm wide, the average width spanned by gamma-H2AX
      positive cells exceeded 150 MUm. Cells adjacent to or in the epidermal layer
      opposite the gamma-H2AX-positive region did not exhibit foci. These findings
      validate this mammalian model as a viable system for investigating radiation
      induced bystander effects in an intact living organism.

PMID- 26207683
TI  - X-Band Rapid-Scan Electron Paramagnetic Resonance of Radiation-Induced Defects in
      Tooth Enamel.
AB  - X-band rapid-scan electron paramagnetic resonance (EPR) spectra from tooth enamel
      samples irradiated with doses of 0.5, 1 and 10 Gy had substantially improved
      signal-to-noise relative to conventional continuous wave EPR. The radiation
      induced signal in a 60 mg of a tooth enamel sample irradiated with a 0.5 Gy dose
      was readily characterized in spectra recorded with 34 min data acquisition times.
      The coefficient of variance of the calculated dose for a 1 Gy irradiated sample,
      based on simulation of the first-derivative spectra for three replicates as the
      sum of native and radiation-induced signals, was 3.9% for continuous wave and
      0.4% for rapid scan.

PMID- 26207685
TI  - The Use of X Rays in the Treatment of Bronchial Asthma: A Historical Assessment.
AB  - This article provides a historical assessment of the role of X-ray therapy in the
      treatment of bronchial asthma. This analysis revealed that X-ray therapy in the
      treatment of bronchial asthma spanned the first six decades of the 20th century,
      and involved nearly 6,000 patients in published clinical case studies. Patients
      selected typically had at least moderate to severe asthma and were refractory to
      other commonly employed treatments. The results of more than 60 studies indicated
      that about 70% of patients had rapid and marked reductions in clinical symptoms
      with about half of these patients showing complete symptom relief. The duration
      of the beneficial responses was variable but was approximately 1-6 months for
      about 50% of the benefited patients, and between 1 to 4 years for the upper 25%
      of benefited patients. The use of X rays to treat such patients fell into
      disfavor during the 1950s due to mounting concerns over possible enhanced risks
      of cancer that coincided with the discoveries and use of antihistamine
      medications, antibiotics and the methyl xanthine bronchodilators aminophylline
      and theophylline.

PMID- 26207684
TI  - Thyroid Dose Estimates for a Cohort of Belarusian Children Exposed to (131)I from
      the Chernobyl Accident: Assessment of Uncertainties.
AB  - Deterministic thyroid radiation doses due to iodine-131 ((131)I) intake were
      reconstructed in a previous article for 11,732 participants of the Belarusian
      American cohort study of thyroid cancer and other thyroid diseases in individuals
      exposed during childhood or adolescence to fallout from the Chernobyl accident.
      The current article describes an assessment of uncertainties in reconstructed
      thyroid doses that accounts for the shared and unshared errors. Using a Monte
      Carlo simulation procedure, 1,000 sets of cohort thyroid doses due to (131)I
      intake were calculated. The arithmetic mean of the stochastic thyroid doses for
      the entire cohort was 0.68 Gy. For two-thirds of the cohort the arithmetic mean
      of individual stochastic thyroid doses was less than 0.5 Gy. The geometric
      standard deviation of stochastic doses varied among cohort members from 1.33 to
      5.12 with an arithmetic mean of 1.76 and a geometric mean of 1.73. The
      uncertainties in thyroid dose were driven by the unshared errors associated with
      the estimates of values of thyroid mass and of the (131)I activity in the thyroid
      of the subject; the contribution of shared errors to the overall uncertainty was
      small. These multiple sets of cohort thyroid doses will be used to evaluate the
      radiation risks of thyroid cancer and noncancer thyroid diseases, taking into
      account the structure of the errors in the dose estimates.

PMID- 26207687
TI  - Acute Effects of Exposure to (56)Fe and (16)O Particles on Learning and Memory.
AB  - Although it has been shown that exposure to HZE particles disrupts cognitive
      performance when tested 2-4 weeks after irradiation, it has not been determined
      whether exposure to HZE particles acutely affects cognitive performance, i.e.,
      within 4-48 h after exposure. The current experiments were designed to determine
      the acute effects of exposure to HZE particles ((16)O and (56)Fe) on cognitive
      performance and whether exposure to HZE particles affected learning or memory, as
      well as to understand the relationship between acute changes in the levels of
      NOX2 (a measure of oxidative stress) and COX2 (a measure of neuroinflammation) in
      specific brain regions and cognitive performance. The results of these studies
      indicate that the acute effects of radiation exposure on cognitive performance
      are on memory, not learning. Further, the acute effects of exposure to HZE
      particles on oxidative stress and neuroinflammation and their relationship to
      cognitive performance indicate that, although the effects of exposure to both
      (56)Fe and (16)O are widespread, only changes in specific regions of the brain
      may be related to changes in cognitive function.

PMID- 26207686
TI  - Contribution of Dual Oxidase 2 (DUOX2) to Hyper-Radiosensitivity in Human Gastric
      Cancer Cells.
AB  - Whole-abdominal radiotherapy (WART) is a primary method for managing
      gastrointestinal cancers that have disseminated into intra-abdominal tissues.
      While effective, this approach is limited because of the increased toxicity to
      normal tissue associated with combined WART and full-dose chemotherapy regimens.
      Recent studies have demonstrated a survival advantage in a novel treatment
      paradigm that allows for the safe use of full-dose systemic chemotherapy in
      combination with low-dose fractionated radiotherapy (LDFRT). Traditionally,
      radiation doses greater than 120 cGy have been used in radiotherapy because lower
      doses were thought to be ineffective for tumor therapy. However, we now know that
      LDFRT can produce hyper-radiosensitivity (HRS), a phenomenon where cells undergo
      apoptosis at radiation doses as low as 15 cGy, in a number of proliferating
      cells. The objectives of our current study were to determine whether LDFRT can
      induce HRS in gastrointestinal cancer cells and to identify biomarkers of
      chemopotentiation by LDFRT. Our data indicate that three consecutive daily
      fractions of 15 cGy produced HRS in gastric cancer cells and potentiated a
      modified regimen of docetaxel, cisplatin and 5'-fluorouracil (mDCF). Colony
      survival assays indicated that 15 cGy was sufficient to kill 90% of the cells
      when LDFRT was combined with mDCF whereas a dose almost 10 times higher (135 cGy)
      was needed to achieve the same rate when using conventional radiotherapy alone.
      RT(2) PCR ProfilerTM array analysis indicated that this combined regimen
      upregulated dual oxidase 2 (DUOX2), an enzyme functioning in the production of
      hydrogen peroxide, without upregulating genes involved in DNA repair. Moreover,
      downregulation of DUOX2 increased radioresistance at every radiation dose tested.
      In addition, our data indicate that reactive oxygen species (ROS) increase up to
      3.5-fold in cells exposed to LDFRT and mDCF. Furthermore, inhibition of NADPH
      oxidase abrogated the killing efficiency of this combined regimen. Taken together
      these data suggest that chemopotentiation by LDFRT in gastric cancer cells may be
      due, at least in part, to increased ROS production (DUOX2) without upregulation
      of the DNA repair machinery. These data thus provide a rationale for further
      explorations of potential clinical applications of LDFRT, such as in WART, as a
      chemopotentiator for advanced and metastatic gastric cancers.

PMID- 26207688
TI  - New Evidence for Hydroxyalkyl Radicals and Light- and Thermally Induced Trapped
      Electron Reactions in Rhamnose.
AB  - Radical formation and trapping of radicals in X-irradiated crystals of rhamnose
      at 6 K were investigated using electron paramagnetic resonance (EPR), electron
      nuclear double resonance (ENDOR) and ENDOR-induced EPR (EIE) techniques,
      complemented with periodic density functional theory (DFT) calculations. The two
      major radical species at 6 K were the O4-centered alkoxy radical and the
      intermolecularly trapped electron (IMTE), previously also detected by other
      authors. The current experimental results provided hyperfine coupling constants
      for these two species in good agreement with the previous data, thus providing a
      consistency check that improves their credibility. In addition to the O4-centered
      alkoxy radical and the IMTE, the C3-centered and C5-centered hydroxyalkyl
      radicals are the most prominent primary species at 6 K. The C3-centered radical
      appears in two slightly different conformations at 6 K, designated C and D. The
      C5-centered radical exhibits a coupling to a methyl group with tunneling rotation
      at 6 K, and analysis of one of the rotational substates (A) of the spin system
      yielded an understanding of the structure of this radical. Visible light
      bleaching of the IMTE at 6 K led to the C3-centered radical C, and thermal
      annealing above 6 K resulted in a conversion of the C to the D conformation. In
      addition, thermal annealing releases the IMTE, apparently resulting in the
      formation of the C2-centered radical. It is possible that the thermal decay of
      the IMTE also contributes to a small part of the C3-centered radical (D)
      population at 85 K. There are several other products trapped in rhamnose crystals
      directly after irradiation at 6 K, among which are resonance lines due to the C2
      H-abstraction product. However, these other products are minority species and
      were not fully characterized in the current work.

PMID- 26207689
TI  - Association of Hematological Nadirs and Survival in a Nonhuman Primate Model of
      Hematopoietic Syndrome of Acute Radiation Syndrome.
AB  - Recombinant human interleukin-12 (rHuIL-12) mitigates the hematopoietic
      subsyndrome of acute radiation syndrome (HSARS) after total body irradiation
      (TBI) in a nonhuman primate (NHP) model of HSARS. The mechanism for this effect
      appears to involve multiple effects of rHuIL-12 on hematopoiesis. We conducted a
      meta-analysis to examine hematological nadirs and survival across our three NHP
      completed studies. Animals were irradiated (700 cGy) and treated with a single
      subcutaneous injection of vehicle (n = 64) or rHuIL-12 (50-500 ng/kg; n = 108) 24
      25 h after irradiation, or with daily subcutaneous injections of granulocyte
      colony stimulating factor (G-CSF; 10 MUg/kg/day) for 18 days starting 24-25 h
      after exposure (n = 26). Blood samples were obtained at various time points up to
      day 60 after TBI. Lymphocytes, neutrophils and platelets were significantly lower
      in nonsurvivors than in survivors in the overall sample and in each treatment
      group (P < 0.001 for each comparison, Wilcoxon rank-sum test). Lymphocyte nadir
      was the strongest and most consistent predictor of death by Spearman's rank
      correlation. Receiver operating characteristic (ROC) curve analysis of death and
      threshold hematologic nadir values (where nadir values less than or equal the
      threshold are predictive of death) showed that a threshold of 0.08 * 10(9)/L for
      lymphocytes had the largest positive predictive value of death (97.2% and 92.5%
      for the control and rHuIL-12 groups, respectively) and high sensitivity (76.1%
      and 62.7%, respectively), consistent with human radiation victims data. The
      current findings suggest that enhanced early bone marrow regeneration resulting
      in increases in nadir values for all major blood cell types may be the main
      mechanism of action by which rHuIL-12 mitigates the lethality of HSARS.

PMID- 26207690
TI  - A Single Low Dose of Proton Radiation Induces Long-Term Behavioral and
      Electrophysiological Changes in Mice.
AB  - Astronauts traveling outside Earth's magnetosphere risk exposure to charged
      particle radiation that may cause neurophysiological changes and behavioral
      deficits. Although proton particles comprise a large portion of the space
      radiation environment, little has been published on the effects of low-dose
      proton radiation on central nervous system function. In the current study, we
      irradiated young male mice with 0.5 Gy 150 MeV protons and assessed the effects
      on behavior and hippocampal neurophysiology. Spatial learning ability, a
      sensitive behavioral marker of hippocampal damage, was assessed using the water
      maze and Barnes maze before irradiation and repeatedly 3 and 6 months after
      irradiation. Evoked field excitatory postsynaptic potentials (fEPSPs) and
      population spikes, long-term potentiation (LTP) and spontaneous oscillations
      (SOs) triggered by incubation with Mg(2+)-free media (reflecting interictal
      epileptiform activity) were assessed 9 months after irradiation in vitro in
      hippocampal slice preparations. Irradiated mice exhibited impaired reversal
      learning in the water maze compared to control mice 6 months after irradiation.
      Proton radiation did not affect LTP, but significantly increased fEPSP slopes and
      reduced the incidence of SOs 9 months after irradiation. These findings suggest
      that a single exposure to low-dose proton radiation can increase synaptic
      excitability and suppress the propensity for epileptiform activity. Such findings
      of functional alterations in the irradiated mouse hippocampus have implications
      for extended manned space missions planned in the near future.

PMID- 26207691
TI  - Verbal fluency as a function of time in autism spectrum disorder: An impairment
      of initiation processes?
AB  - In the present study, we aimed to evaluate the hypothesis that the reported
      discrepancy in the performance of verbal fluency in individuals with autism
      spectrum disorder (ASD), characterized by an overall word productivity impairment
      with normal clustering and switching abilities, may be due to an initiation
      deficit. In the present study, we evaluated the temporal dynamics of both letter
      and semantic verbal fluency tasks in a sample of 20 young adults with high
      functioning ASD compared with a sample of 20 gender-, age-, education-, and
      verbal-IQ-matched participants. We first compared both the word productivity and
      the qualitative analysis of clustering and switching abilities during the entire
      task to replicate the discrepancy reported in the literature. Importantly, we
      next analyzed both word productivity and clustering and switching abilities in
      two time intervals (0-30 s and 31-60 s), as it was our primary interest to
      evaluate the functioning of the initial component of word retrieval. Directly
      supporting the idea that the discrepancy found between an impairment in global
      word productivity combined with normal clustering and switching strategies is due
      to an activation and initiation deficit, we observed an abnormal performance for
      the ASD group in the first time period only. We interpreted these results to be
      preliminary findings of deficits in initiation processes in ASD. 

PMID- 26207692
TI  - Robotic single docking total colectomy for ulcerative colitis: First experience
      with a novel technique.
AB  - INTRODUCTION: We describe a novel technique that could aid the surgeon to perform
      a total proctocolectomy with a single docking position of the da Vinci Si HD
      System. METHODS: Patients were positioned in 20 degrees  Trendelenburg lithotomy
      split legs position. A 12-mm trocar was for camera and 3 more trocars were
      placed: two robotics on left and right flanks and one laparoscopic in left iliac
      fossa. The robot was docked between the legs of the patients. RESULTS: Four
      proctocolectomies were performed. Mean operative time was 235 min (range 215
      255); mean blood loss was 100 cc (range 50-200). Median post-operative stay was 6
      days. Overall morbidity was 75%, whereas major complications occurred in 25%.
      Post-operative mortality was null. CONCLUSIONS: The robotic single docking
      approach to perform total proctocolectomy for ulcerative colitis is a time-saving
      technique respect to the multiple docking approach.

PMID- 26207693
TI  - Vacuolization in Cytoplasm and Cell Membrane Permeability Enhancement Triggered
      by Micrometer-Sized Graphene Oxide.
AB  - A deep understanding of the interaction of a graphene oxide (GO) sheet with cells
      at the molecular level may expedite its biomedical application and predict its
      new functions and adverse effects. Herein we inspect the interaction between
      micrometer-sized GO (mGO), commonly used in biomedical research, and cells at the
      molecular level through a variety of techniques. A major finding is that, instead
      of direct cellular penetration, the mGO sheets can stimulate the cellular
      response by interacting with the membrane protein and the membrane. Specifically,
      it is illustrated that even within a short exposure time the mGO sheets can
      induce the formation of vacuoles in the cytosolic compartment and enhance the
      cell permeability. The vacuolization is only observed in the cells that strongly
      express aquaporin (AQP1), indicating the specific interaction of the mGO with
      AQP1. Moreover, inhibition of the AQP1 activity prevents the formation of
      vacuoles, revealing that the interaction of the mGO with AQP1 occurs most
      probably at the vestibule of AQP1 at the extracellular side. Additionally, though
      the cell permeability was enhanced, it only improves the penetration of small
      molecules, not for macromolecules such as proteins. These findings are
      potentially valuable in cancer therapy because AQPs are strongly expressed in
      tumor cells of different origins, particularly aggressive tumors, and it will
      also be beneficial for drug transport across barrier membranes. 

PMID- 26207694
TI  - Treatment of Massive Labial and Gingival Hypertrophy in a Patient With Infantile
      Systemic Hyalinosis-A Case Report.
AB  - Infantile systemic hyalinosis (ISH) is a rare autosomal recessive disorder caused
      by a mutation in the ANTXR2 gene encoding a transmembranous protein involved in
      endothelial development. The ANTXR2 (also known as CMG2) locus is on chromosome
      4q21. ISH is a common disorder in children of consanguineous parents in Arab
      countries. Symptoms of ISH manifest within the first months of life as
      progressive painful joint contractures and edema, hyperpigmentation of the skin,
      cutaneous nodules, persistent diarrhea with protein-losing enteropathy, and
      recurrent infections. Children affected by ISH often die undiagnosed in infancy.
      Histopathologic examination shows hyaline deposits in the skin, skeletal muscles,
      cardiac muscle, lymph nodes, adrenal glands, gastrointestinal tract, thyroid, and
      spleen. Hyaline deposits are the result of leakage of plasma components to the
      perivascular space owing to defective endothelial morphogenesis. ISH manifests
      most often in the facial region. Patients develop hypertrophy of labial and
      buccal tissues and massive gingival overgrowths, which impair oral food intake
      and maintenance of satisfactory oral hygiene. The differential diagnosis of ISH
      should consider juvenile systemic hyalinosis (an allelic variant of ISH),
      Winchester syndrome, systemic fibromatosis, stiff skin syndrome, lipoid
      proteinosis, mucopolysaccharidosis, sphingolipidosis, and mucolipidosis. This
      report describes a case of massive labial and gingival hypertrophy in a 6-year
      old boy with ISH. 

PMID- 26207695
TI  - Ameloblastic Fibrosarcoma of the Mandible With Distant Metastases.
AB  - Ameloblastic fibrosarcoma is a mixed odontogenic tumor that can originate de novo
      or from a transformed ameloblastic fibroma. This report describes the case of a
      34-year-old woman with a recurrent, rapidly growing, debilitating lesion. This
      lesion appeared as a large painful mandibular swelling that filled the oral
      cavity and extended to the infratemporal fossa. The lesion had been previously
      misdiagnosed as ameloblastoma. Twenty months after final surgery and
      postoperative chemotherapy, lung metastases were diagnosed after she reported
      respiratory signs and symptoms. 

PMID- 26207696
TI  - Management of false passage created during hysteroscopic adhesiolysis for
      Asherman's syndrome.
AB  - False passage in the uterus, if unrecognised, will almost certainly lead to
      perforation of the uterus and associated complications. We present our experience
      of the management of a false passage encountered during hysteroscopic surgery for
      the treatment of severe Asherman's syndrome. Five women with severe Asherman's
      syndrome resulting in complete obliteration of the uterine cavity and a false
      passage created during hysteroscopy were included in our study. A subsequent
      hysteroscopy was performed under ultrasound guidance with preoperative oestrogen
      therapy to increase endometrial thickness. In all 5 cases, the uterine cavity was
      successfully entered during the repeat hysteroscopy, which enabled the
      adhesiolysis procedure to be completed. There was satisfactory improvement in
      menstrual pattern and significant reduction in intrauterine the adhesion score.
      Two of the three patients who wished to conceive did become pregnant. The early
      recognition of a false passage inadvertently created during hysteroscopy is
      crucial in preventing further damage to the uterus. 

PMID- 26207697
TI  - Regulation of 26S Proteasome Activity in Pulmonary Fibrosis.
AB  - RATIONALE: The ubiquitin-proteasome system is critical for maintenance of protein
      homeostasis by degrading polyubiquitinated proteins in a spatially and temporally
      controlled manner. Cell and protein homeostasis are altered upon pathological
      tissue remodeling. Dysregulation of the proteasome has been reported for several
      chronic diseases of the heart, brain, and lung. We hypothesized that proteasome
      function is altered upon fibrotic lung remodeling, thereby contributing to the
      pathogenesis of idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To investigate
      proteasome function during myofibroblast differentiation. METHODS: We treated
      lung fibroblasts with transforming growth factor (TGF)-beta and examined
      proteasome composition and activity. For in vivo analysis, we used mouse models
      of lung fibrosis and fibrotic human lung tissue. MEASUREMENTS AND MAIN RESULTS:
      We demonstrate that induction of myofibroblast differentiation by TGF-beta
      involves activation of the 26S proteasome, which is critically dependent on the
      regulatory subunit Rpn6. Silencing of Rpn6 in primary human lung fibroblasts
      counteracted TGF-beta-induced myofibroblast differentiation. Activation of the
      26S proteasome and increased expression of Rpn6 were detected during bleomycin
      induced lung remodeling and fibrosis. Importantly, Rpn6 is overexpressed in
      myofibroblasts and basal cells of the bronchiolar epithelium in lungs of patients
      with IPF, which is accompanied by enhanced protein polyubiquitination.
      CONCLUSIONS: We identified Rpn6-dependent 26S proteasome activation as an
      essential feature of myofibroblast differentiation in vitro and in vivo, and our
      results suggest it has an important role in IPF pathogenesis.

PMID- 26207699
TI  - Organocatalytic Synthesis of Alkynes.
AB  - Carbon-carbon triple bonds of alkynes are ubiquitous. They serve as valuable
      starting materials that can be transformed into a vast array of diverse
      materials, with applications ranging from medicinal chemistry to electronic
      materials. The methods used to prepare alkynes involve stoichiometric reactions
      and the most popular install only a single carbon rather than uniting larger
      fragments. These methods are useful, but they are limited by harsh conditions or
      the need to prepare reagents. Introduced herein is the first catalytic method to
      prepare carbon-carbon triple bonds from precursors that do not contain such
      linkages. By coupling benzaldehyde and benzyl chloride derivatives under basic
      conditions with an organocatalyst, good yields of alkynes are obtained. The
      catalyst, a highly reactive sulfenate anion, is readily generated under the
      reaction conditions from air-stable precursors. This method represents an
      attractive organocatalytic alternative to well-established stoichiometric
      approaches to alkynes and to transition-metal-based alkyne functionalization
      methods in various applications. 

PMID- 26207698
TI  - Meeting the Needs of Male Caregivers by Increasing Access to Accountable Care
      Organizations.
AB  - As the population of male caregivers continues to grow over time, they have
      become more visible to the service system. However, as the vast majority of
      supports serve female caregivers, it is important to bring men "inside" of the
      service system. Following a review of the male caregiver experience, this
      commentary discusses how Accountable Care Organizations (ACOs), a provision of
      the Patient Protection and Affordable Care Act of 2010, is one way that men can
      be brought into and access the service system. Although male caregivers are the
      focus of this paper, the recommendations suggested are useful for professionals
      working with all caregivers regardless of gender. Discussion includes a rationale
      as to why ACOs are a unique service that are currently being developed that
      provides a window of opportunity for health professionals to meet caregiver needs
      in new ways. This would include the evaluation of and addressing male caregiver
      psychosocial and support needs at the time of addressing care receivers' medical
      needs. 

PMID- 26207700
TI  - The Power of 2.5 Million Words.
AB  - Today, I am writing for the first time as the new editor of the Clinical Journal
      of Oncology Nursing (CJON). It is my honor to assume this role from my colleague
      and mentor, Deborah K. Mayer, PhD, RN, AOCN, FAAN. For eight years, Deb served as
      the editor of one of the most widely read journals in oncology nursing, CJON. ?.

PMID- 26207701
TI  - Supporting the Couple With Female Dyspareunia.
AB  - Patients receiving treatment for cancer often experience changes in sexual
      functioning but may be hesitant to ask questions. This article focuses on ways in
      which nurses can support patients and their partners and address their concerns
      through various evidence-based interventions. At a Glance * Sexuality, as well as
      how it is affected by cancer and its treatment, is an important aspect of
      holistic nursing care. * Sexuality is not often brought up by nurses because of
      concern about a lack of evidence-based interventions. * Many of the skills needed
      to inquire about sexual concerns are those that nurses use daily: active
      listening, sensitivity, and knowledge about how cancer and its treatment can
      physiologically affect sexual functioning.

PMID- 26207702
TI  - Minimizing Staff Exposure to Antineoplastic Agents ?During Intravesical Therapy.
AB  - Exposure to chemotherapy is a daily risk for nurses in oncology infusion centers.
      Although significant advances have been made in developing systems to make IV
      administration of antineoplastic agents safer, less attention has been given to
      developing systems to minimize exposure risk during instillation of intravesical
      chemotherapy. This article describes the use of a closed system developed at a
      comprehensive cancer center and compares it to two closed systems reported in the
      literature. At a Glance * Safe handling of biohazard medications is important for
      all healthcare workers involved in the administration of antineoplastic agents. *
      Nurses need to advocate for use of chemotherapy administration systems that
      minimize exposure to staff and patients. * Infrequently performed procedures need
      to be supported by clearly specified procedural steps that are readily accessible
      to the nurse.

PMID- 26207703
TI  - Informal Caregivers' Knowledge and Practice ?of Caring for Neutropenic Patients.
AB  - Cooperation of informal caregivers on neutropenic patient care is very important.
      This descriptive study includes interviews with 100 informal caregivers of
      inpatients who became neutropenic at least two days previously. Data were
      collected through face-to-face interviews on informal caregivers' knowledge and
      practice of caring for patients with neutropenia. The authors found that some
      rules, such as washing hands and attention to personal cleaning, were known and
      practiced; other rules, such as having a bath every other day, were less well
      known. At a Glance * Caregivers should be provided with regular training and
      standard education programs. * Informal caregivers should be observed when
      engaged in their routines to assess whether their practice is appropriate in
      neutropenic patient caring, and nurses should check whether or not their
      recommendations are being applied and ensure any deficiencies are addressed. *
      The verbal instruction provided by nurses for caregivers does not include enough
      information about care for neutropenic patients.

PMID- 26207704
TI  - Using Technology for Distraction During Imaging in a Pediatric Population.
AB  - Magnetic resonance imaging (MRI) simulation and audiovisual (AV) devices are
      technological tools that can improve the patient experience during imaging
      procedures and lead to overall healthcare benefits for patients, healthcare
      providers, and institutions. AV devices, such as MRI-compatible goggles and
      headphones, offer the potential to improve the patient experience. These options
      can be offered to patients who describe negative feelings, including anxiety,
      prior to imaging. Nurses can advocate for these resources for an improved patient
      experience. At a Glance * Nurses should offer new tools, including simulation and
      audiovisual devices, to patients prior to and during magnetic resonance imaging.
      * These technologies help predict if a patient will have a successful imaging
      procedure and may improve the patient experience during imaging. * Patients and
      institutions stand to benefit from less medical interventions, such as
      anesthesia, and reduced long-term costs.

PMID- 26207705
TI  - Improving Patient Safety and Satisfaction ?With Standardized Bedside Handoff and
      Walking Rounds.
AB  - In 2009, the Joint Commission identified a standardized approach to handoff
      communication as a patient safety goal to reduce communication errors. Evidence
      suggests that a structured handoff report, combined with active patient
      participation, reduces communication errors and promotes patient safety. Research
      shows that bedside handoff increases nurses' accountability by visualizing the
      patient and exchanging information at the point of care. Based on recommendations
      from the Joint Commission, the Robert Wood Johnson Foundation, and broader
      research literature, a standardized approach to bedside handoff and walking
      rounds was implemented on an inpatient surgical oncology unit. At a Glance * A
      standardized handoff communication tool is recognized as a Joint Commission
      patient safety goal to reduce communication errors and improve patient safety. *
      The benefits of patient safety and satisfaction outweigh the barriers to
      implementing a bedside handoff report. * A standardized, nurse-driven, electronic
      report should guide transfer of information during bedside handoff.

PMID- 26207706
TI  - Obtaining Coagulation Blood Samples From Central Venous Access Devices: A Review
      of the Literature.
AB  - BACKGROUND: Central venous access devices are used for chemotherapy and other
      medication administration, blood product administration, parenteral nutrition,
      and for obtaining blood samples in patients where the vasculature is difficult to
      access. Patients may need additional blood samples prior to invasive procedures
      and when clinical situations arise during cancer care. In addition, monitoring
      coagulability through ongoing blood testing is common in patients with cancer and
      requires repeated sampling to adjust anticoagulant medications. OBJECTIVES: The
      purpose of this review of the literature is to determine the best practices for
      collecting coagulation test samples from central venous access devices. METHODS:
      The authors conducted a systematic review of the literature. FINDINGS: The only
      method for obtaining reliable coagulation test results from central venous access
      devices is the flush then waste/discard method. This method has only been studied
      with peripherally inserted central catheters. Additional randomized, controlled
      trials with larger sample sizes are needed to determine the most appropriate
      method for drawing coagulation test results from central venous access devices.

PMID- 26207707
TI  - Nivolumab: Immunotherapy in Malignant Melanoma.
AB  - BACKGROUND: Although patients diagnosed with melanoma that is confined to the
      skin have a five-year survival rate of 98%, this number drops to 16% with widely
      metastatic disease. Melanoma rates have been steadily increasing since the 1970s,
      but cytotoxic chemotherapy generally prolongs survival by about four months.
      Nivolumab is an effective immunotherapy agent. OBJECTIVES: This article discusses
      the use of nivolumab for metastatic melanoma. METHODS: Clinical trial and early
      postmarketing data were reviewed. FINDINGS: In clinical trials, patients with
      advanced melanoma experienced partial sustained responses to nivolumab, a new
      targeted immunotherapy agent, for more than one year. Nivolumab helps the immune
      system mobilize lymphocytes that have been inactivated by melanoma cells,
      enhancing the body's ability to recognize the cancer as abnormal. Compared to
      conventional chemotherapy, nivolumab has been shown to greatly improve survival
      in widespread, inoperable malignant melanoma. Oncology nurses will administer,
      monitor, and educate patients about nivolumab.

PMID- 26207708
TI  - Delayed Chemotherapy-Induced Nausea and Vomiting in the Hematology Population: A
      Review of the Literature.
AB  - BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is one of the most
      bothersome problems experienced by patients with cancer and results in serious
      complications. Considerable progress has been made in the management of acute
      CINV, but many patients receiving chemotherapy still complain of delayed nausea.
      In particular, delayed CINV affects patients in the hematology population who
      typically undergo several frontline chemotherapy regimens, multiday conditioning
      regimens, and salvage treatments. However, no international guidelines exist for
      the prevention of CINV in this population. OBJECTIVES: This article provides a
      literature review of the pathophysiologic mechanisms of delayed CINV as well as
      the etiologies, assessment strategies, and potential therapies in this
      population. METHODS: A narrative review of the literature was performed.
      FINDINGS: Nurses fulfill an important role in the assessment of delayed symptoms
      by ensuring adequate measurement of the duration, frequency, severity, and
      distress caused by nausea, vomiting, and retching. A systematic assessment of
      retching, in addition to nausea and vomiting, that involves patients' assessment
      of their own symptoms may enhance the accuracy of clinical reports, leading to
      improved tolerability of chemotherapy and patient quality of life. In addition,
      nurses may actively contribute to the development of specific guidelines for
      hematologic malignancies and a patient risk factor algorithm for optimizing the
      tolerability of chemotherapy.

PMID- 26207709
TI  - Lack of Support and Information Regarding Long-Term Negative Effects in Survivors
      of Rectal Cancer.
AB  - BACKGROUND: Rectal cancer is a common cancer. Curative treatment frequently
      includes surgery, radiation, and chemotherapy, all of which can result in long
      term adverse effects. OBJECTIVES: This descriptive, hypothesis-generating study
      sought to obtain input from survivors of rectal cancer regarding key features of
      their long-term experience. METHODS: The authors administered a 12-question,
      Internet-based survey to self-identified rectal cancer survivors to assess (a)
      how neuropathy, fatigue, trouble with ostomy or bowel movements, and trouble with
      sexual function affect daily life and (b) whether knowing about these symptoms a
      priori would have changed their treatment decisions. Responses are presented
      descriptively. Qualitative analysis assessed themes reported in response to an
      open-ended question. FINDINGS: Responses from 116 survivors of rectal cancer, 55
      of whom provided open-ended responses, were obtained. Respondents were
      predominantly young and several years from treatment. They reported that their
      lives were affected "a lot" by bowel or ostomy trouble, trouble with sexual
      function, fatigue, and nerve toxicity. Survivors reported that knowing whether
      symptoms would affect their lives "a lot" would have changed their treatment
      decisions with a priori knowledge of these lasting effects. Key qualitative
      themes were the lack of information about and support for negative effects.

PMID- 26207710
TI  - Optimal Topical Agent for Radiation Dermatitis During Breast Radiotherapy: A
      Pilot Study.
AB  - BACKGROUND: Women receiving radiation to the breast will likely be recommended to
      use a topical cream to minimize and delay the development of radiation
      dermatitis. Although many topical products are commercially available and have
      been tested for safety and efficacy, few studies have compared various products
      to one another for superiority and cost effectiveness. OBJECTIVES: The purpose of
      this pilot study was to compare three commonly used skin care products
      prospectively to one other in a homogenously controlled group of women undergoing
      whole breast irradiation to assess superiority in minimizing the common toxicity
      criteria grade of radiation dermatitis, effect on quality of life, and cost.
      METHODS: The authors conducted a systematic review to determine the three types
      of skin care products with the strongest evidence of minimizing radiation
      dermatitis. Patients were voluntarily enrolled and randomized to one of three
      possible skin care topical regimens. Patients completed a quality-of-life survey
      to assess their preference in topical skin care regimen. The cost of each arm's
      topical product was assessed at the completion of patient participation.
      FINDINGS: No statistical difference was noted in the severity or occurrence of
      radiation dermatitis among the groups. In addition, no statistical difference was
      found among the three treatment arms in quality-of-life score changes, and no
      patients required a treatment interruption in their radiation or in the skin care
      product during treatment. A cost difference among the treatment arms was noted.

PMID- 26207711
TI  - Breast Cancer Survivors and Sexuality: A Review of the Literature Concerning
      Sexual Functioning, Assessment Tools, and Evidence-Based Interventions.
AB  - BACKGROUND: Most breast cancer survivors (BCSs) experience sexual dysfunction
      from treatment-induced hormonal changes, making sexual assessment an important
      component of survivorship care. However, because many oncology healthcare
      providers do not perform such assessment, a number of BCSs endure unidentified
      sexual dysfunction. Barriers to assessment faced by providers must be identified,
      and further research should examine the perspectives of BCSs and their partners
      regarding preferences for sexual assessment and interventions. OBJECTIVES: The
      purpose of this literature review was to explore tools used to assess sexual
      functioning and evidence-based interventions used to treat sexual dysfunction in
      BCSs. METHODS: Articles published from 2003-2013 that reported on the effects of
      breast cancer and its treatment on sexual functioning in BCSs and located through
      online database searches (PubMed, the Cochrane Library, MEDLINE, CINAHL) were
      reviewed. FINDINGS: Sexual dysfunction is a common problem among BCSs. Using
      various assessment tools, providers should regularly assess sexual functioning in
      BCSs during and after treatment to improve quality of life for BCSs and their
      partners.

PMID- 26207712
TI  - Implementing a Primary Healthcare Framework: The Importance of Nursing Leadership
      in Developing and Maintaining a Brain Tumor Support Group.
AB  - BACKGROUND: Although brain tumor support groups have been available
      internationally for many years, Liverpool Hospital in Australia has not
      traditionally provided this service. As a leadership initiative, the development
      of a brain tumor support group that incorporates a primary healthcare framework
      is a sustainable approach that showcases the role of nursing leaders in changing
      attitudes and improving outcomes. OBJECTIVES: The purpose of this review of the
      literature and reflection of clinical experience is to explore nursing leadership
      within brain tumor-specific support groups. METHODS: This article will showcase a
      nurse-led group that incorporated a coordinated approach to delivering patient
      centered care. FINDINGS: The initiation of activities and interventions that
      reflected the five tenets of primary health care resulted in improved outcomes
      for individuals and their family caregivers throughout the trajectory of their
      illness. Vital to the success of this project was moving from a standalone leader
      to building collective and collaborative leadership more conducive to
      facilitating change. The support group successfully demonstrated that individuals
      and family caregivers may see ongoing and long-term improvements during and
      following treatment.

PMID- 26207713
TI  - Stomatitis Associated With Use of mTOR Inhibitors: Implications for Patients With
      Invasive Breast Cancer.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor everolimus is
      approved (in combination with exemestane) for the treatment of postmenopausal
      women with advanced hormone receptor-positive, human epidermal growth factor
      receptor 2-negative breast cancer resistant to endocrine therapy. Stomatitis is
      among the most frequently reported dose-limiting adverse events associated with
      everolimus use, often requiring treatment interruption or dose reduction.
      OBJECTIVES: This article aims to educate nurses on the identification and
      management of stomatitis associated with mTOR inhibitors in hormone receptor
      positive advanced breast cancer and to assist nurses with additional management
      techniques to improve patient outcomes. METHODS: An evaluation of the literature
      highlighting the incidence, identification, and management of stomatitis in
      cancer was performed with a particular focus on breast cancer. In addition, the
      experiences of the authors' cancer center on managing stomatitis are described.
      FINDINGS: A growing body of clinical evidence shows the benefits of adding
      steroid-based mouth rinses to the treatment plan. Clinical experience provides
      additional insight into stomatitis preventive and management strategies for
      patients with breast cancer receiving treatment with everolimus.

PMID- 26207714
TI  - Current Perspectives in the Management of Brain Metastases.
AB  - Brain metastases (BMs) are diagnosed in 10%-40% of all patients with cancer, and
      the incidence continues to increase along with the number of long-term survivors.
      When BMs occur, they are often associated with a myriad of symptoms, including
      neurologic dysfunction and functional decline; both are difficult to manage and
      can be distressing for patients and their caregivers. Although clinically
      significant findings have not kept up with the rapid pace of scientific
      breakthroughs in understanding the mechanisms of BMs, novel approaches that
      affect the prognosis of patients with BMs have been introduced in clinical
      practice. At a Glance * Screening for brain metastases (BMs) is not routinely
      performed in patients with no neurologic symptoms. However, screening is
      indicated in lung cancer and possibly in the context of high-risk cancers. *
      Individual differences in patients warrant a personalized approach in the
      management of BMs. * Whole brain radiation therapy and steroids are considered to
      be the cornerstones of treatment for BMs.

PMID- 26207715
TI  - Total Pancreatectomy With Islet Cell Transplantation?for the Treatment of
      Pancreatic Cancer.
AB  - Resection or removal of the pancreas causes loss of parenchyma, which can result
      in extreme disruption of glucose homeostasis and malabsorption of dietary
      nutrients. However, islet autotransplantation (IAT) may reduce or prevent the
      severity of pancreatogenic diabetes. This article explores total pancreatectomy
      with IAT within the context of pancreatic cancer treatment. At a Glance * The
      liver is the preferred site for implantation because of easy vascular access. *
      Following islet autotransplantation, the liver becomes an insulin-producing organ
      as the transplanted beta cells begin making insulin. * The most significant
      complication of implantation in the liver is portal vein occlusion because of
      thrombosis; consequently, a heparin drip is infused for the first seven days
      postoperatively to prevent portal vein thrombus formation.

PMID- 26207716
TI  - Changing Nursing Practice in Survivorship Care With Clinical Decision Tools.
AB  - The paradigm shift to include survivorship care as part of the cancer care
      continuum underscores the critical need for a change in nursing practice. One way
      to ensure that change in practice is delivered in a safe and efficient manner is
      through the use of clinical decision tools (CDTs). Such tools can be used to
      increase relevant knowledge and skills of nurses and patients. Despite the
      widespread recognition of their value, CDTs to educate providers on cancer
      survivors' care are limited and, when available, often are not used. Clinical
      practice algorithms were developed for disease-specific survivorship clinics in a
      cancer academic center. This article reviews the conceptual framework of the
      survivorship algorithms, describes the application of the algorithms in
      multidisciplinary disease-specific survivorship clinics, and discusses the
      implementation strategies used to promote clinicians' adoption and implementation
      of the algorithms. At a Glance * The authors found that algorithms can be
      successfully used as clinical decision tools(CDTs) to deliver survivorship care.
      * Algorithms and other CDTs are powerful tools to enhance professional practice.
      * Additional studies are needed to assess their effect on clinical practice and
      survivor outcomes.

PMID- 26207717
TI  - Diaries for Recovery From Critical Illness.
AB  - Objective? To assess the effect of a diary versus no diary during a patient's
      recovery from admission to the intensive care unit (ICU).

PMID- 26207718
TI  - One Common Goal and One Unified Wish: ?A Cure for Acute Leukemia.
AB  - Relationship-based care (RBC) is a theoretical framework best described as "when
      nurses and their colleagues own their practice and consciously create
      environments of healing, their efforts visibly affect the practitioners, the
      practice, and the physical space" (Koloroutis, 2004, p. 24). The Arthur G. James
      Cancer Hospital and Richard J. Solove Research Institute in Columbus, Ohio,
      adopted RBC in 2005 as the theoretic framework to guide nursing practice. As the
      RBC council of the 10E James Acute Leukemia Unit began working on primary
      nursing, they realized the need for a unit RBC project to inspire and unify staff
      to the newly developed unit vision. ?. 

PMID- 26207719
TI  - Multifactor Analysis of Malposition of Peripherally Inserted Central Catheters in
      Patients With Cancer.
AB  - BACKGROUND: Peripherally inserted central catheters (PICCs) are used widely in
      patients with cancer, but catheter malposition often occurs. OBJECTIVES: This
      study aimed to provide a reference for clinically safe catheterization through
      multifactor analysis of malposition of PICCs in patients with cancer. METHODS:
      The occurrence of PICC malposition in patients with cancer was retrospectively
      reviewed, and a multivariate logistic regression analysis was performed.
      FINDINGS: Of 2,084 patients with PICCs, 170 cases (8%) of malposition occurred.
      The multivariate logistic regression analysis revealed that the risk of adverse
      events from malposition was higher in the right upper limb than in the left upper
      limb. The highest risk from malposition was cephalic vein puncture, followed by
      brachial vein puncture. The risk in the lower part of the elbow joint was higher
      than that in the upper part of the elbow joint. During PICC insertion, the left
      upper limb and upper part of the elbow joint should be selected for the puncture,
      and the basilic vein should be selected as the first-choice vein to reduce the
      incidence of malposition and adverse events.

PMID- 26207720
TI  - Transitions of Care: A Hematopoietic Stem Cell Transplantation Nursing Education
      Project Across the Trajectory.
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HCT) is a complicated
      treatment modality used to address hematologic malignancies and other disorders.
      The complex care of patients undergoing HCT places them at high risk for poor
      outcomes during times of transition. Education is a critical component of
      preparing patients and caregivers to move through the many phases of the HCT
      treatment trajectory (i.e., preadmission, preparative regimens, inpatient
      admission, discharge, outpatient management, survivorship). OBJECTIVES: The
      purpose of this article is to provide a useful systematic approach to the
      standardization of patient teaching methods across various professional nursing
      roles in the HCT trajectory (i.e., nurse coordinator, midlevel staff, case
      manager, inpatient nurse, day hospital nurse) in an effort to improve outcomes
      related to patient transitions. METHODS: A performance improvement project based
      on physician and health services researcher Avedis Donabedian's conceptual
      framework was implemented at a National Cancer Institute-designated comprehensive
      cancer center in the western United States, with the intention of enhancing
      nurses' knowledge and standardizing the education of patients undergoing HCT and
      their caregivers from pretransplantation to survivorship. FINDINGS: Donabedian's
      framework was a helpful model in enacting changes focused on transitions in care
      for the population of patients undergoing transplantation. For this population,
      implementing and sustaining coordinated care across multiple nursing roles in a
      treatment trajectory is complex. However, early possible indicators of success
      (e.g., decreased length of stay, lower readmission rates) were promising
      outcomes.

PMID- 26207721
TI  - Integrating Geriatrics Into Oncology Ambulatory Care Clinics.
AB  - BACKGROUND: Geriatric oncology offers specialized care that incorporates
      comprehensive geriatric assessment (CGA) and multidisciplinary teams (MDTs) with
      oncology care. Geriatric syndromes, comorbidities, and caregiver concerns are
      relevant to the oncology assessment in older adult patients to make treatment
      decisions, which should be based not on age but on health and functional status,
      as well as on life expectancy. Developing a geriatric oncology ambulatory care
      clinic (GOACC) requires numerous resources and entails planning for longer
      patient encounter times, devising collaboration strategies with community care
      providers, and establishing dedicated time for team members. OBJECTIVES: The
      purpose of this article is to provide information regarding the construction and
      sustainability of a GOACC. METHODS: A comprehensive review of literature
      published from 1991-2015 was conducted using the following key words. FINDINGS:
      Oncology primary care nurses and advanced practice nurses have a large role in
      the development and maintenance of GOACCs. Managing comorbidities, identifying
      patients who likely would benefit from a CGA, providing caregiver support,
      conducting a CGA, and creating an MDT are core elements of developing a
      sustainable GOACC.

PMID- 26207722
TI  - Wound Dressings During Radiotherapy for Cancer: A Survey of Practice.
AB  - BACKGROUND: Patients undergoing radiotherapy may experience changes to the skin
      that require dressings. Recommendations regarding radiating through wound
      dressings have been variable and relate to the concern regarding surface dose
      increase or bolus effect. OBJECTIVES: The purpose of this article is to identify
      current evidence and practice through literature review and a national
      environmental scan. METHODS: Nurses from 18 radiation oncology centers in Canada
      were surveyed about current practice. In-depth telephone interviews were
      conducted with four nurse participants to further understand the context of this
      issue within the nursing practice environment. FINDINGS: The integrated results
      of the study were reviewed with five clinical experts to make recommendations for
      research, practice, leadership, and policy. Implications for clinical practice
      included the involvement of radiation oncology nurses in the treatment planning
      team, development of clinical practice tools, and the relevance of the Person
      Centered Nursing framework for wound management during radiotherapy.

PMID- 26207723
TI  - Intrinsic Polarization and Tunable Color of Electroluminescence from Organic
      Single Crystal-based Light-Emitting Devices.
AB  - A single crystal-based organic light-emitting device (OLED) with intrinsically
      polarized and color-tunable electroluminescence (EL) has been demonstrated
      without any subsequent treatment. The polarization ratio of 5:1 for the
      transversal-electric (TE) and transversal-magnetic (TM) polarization at the
      emission peak of 575 nm, and 4.7:1 for the TM to TE polarization at the emission
      peak of 635 nm, respectively, have been obtained. The emitting color is tunable
      between yellow, yellow-green and orange by changing the polarization angle. The
      polarized EL and the polarization-induced color tunability can be attributed to
      the anisotropic microcavity formed by the BP3T crystal with uniaxial alignment of
      the molecules.

PMID- 26207724
TI  - Respiratory effects of air pollution on children.
AB  - A substantial proportion of the global burden of disease is directly or
      indirectly attributable to exposure to air pollution. Exposures occurring during
      the periods of organogenesis and rapid lung growth during fetal development and
      early post-natal life are especially damaging. In this State of the Art review,
      we discuss air toxicants impacting on children's respiratory health, routes of
      exposure with an emphasis on unique pathways relevant to young children, methods
      of exposure assessment and their limitations and the adverse health consequences
      of exposures. Finally, we point out gaps in knowledge and research needs in this
      area. A greater understanding of the adverse health consequences of exposure to
      air pollution in early life is required to encourage policy makers to reduce such
      exposures and improve human health.

PMID- 26207725
TI  - Plasma apolipoprotein A1 associates with age at onset and motor severity in early
      Parkinson's disease patients.
AB  - BACKGROUND: Development of robust plasma-based biomarkers in Parkinson's disease
      (PD) could lead to new approaches for identifying those at risk for PD and
      developing novel therapies. Here, we validate plasma apolipoprotein A1 (ApoA1) as
      a correlate of age at onset and motor severity in PD. METHODS: Plasma ApoA1 and
      high-density lipoprotein at baseline, 6 months, and 12 months were measured in
      254 research volunteers (154 patients with PD and 100 normal controls) enrolled
      in the Parkinson's Progression Markers Initiative (PPMI) study. RESULTS: Lower
      baseline plasma ApoA1 levels associate with an earlier age at PD onset in early
      stage, drug-naive PPMI PD patients (P = 0.023). Moreover, lower baseline ApoA1
      levels trend toward association with worse motor severity in PPMI PD patients (p
      = 0.080). Over 12 months of follow-up, plasma ApoA1 levels do not predict motor
      decline in the PPMI PD cohort. Finally, a meta-analysis of five PD cohorts
      encompassing >1,000 patients confirms significant association of lower plasma
      ApoA1 with earlier age at PD onset (P < 0.001) and greater motor severity (P <
      0.001). CONCLUSIONS: Our results confirm the previously reported association of
      lower plasma ApoA1 levels with two clinical features suggesting poorer
      dopaminergic system integrity-earlier age at PD onset and greater motor severity
      in early-stage, drug-naive PD patients. This is the first report of a plasma
      based biomarker evaluated in the PPMI study. Future investigations are warranted
      evaluating plasma ApoA1 as a longitudinal correlate of disease progression as
      well as investigating the potential of ApoA1 as a therapeutic target in PD.

PMID- 26207726
TI  - Mammaglobin 1 promotes breast cancer malignancy and confers sensitivity to
      anticancer drugs.
AB  - Mammaglobin 1 (MGB1), a member of the secretoglobin family, is expressed in
      mammary epithelial tissues and is overexpressed in most mammary carcinomas.
      Despite the extensive research correlating MGB1 expression profiles to breast
      cancer pathogenesis and disease outcome, the biological significance of MGB1 in
      cancer processes is still unclear. We have thus set out to conduct a functional
      evaluation of the molecular and cellular roles of MGB1 in breast cancer processes
      leading to disease progression. Using a series of breast cancer cell models with
      conditional MGB1 expression, we demonstrate that MGB1 promotes cancer cell
      malignant features. More specifically, loss of MGB1 expression resulted in a
      decrease of cell proliferation, soft agar spheroid formation, migration, and
      invasion capacities of breast cancer cells. Concomitantly, we also observed that
      MGB1 expression activates signaling pathways mediated by MAPK members (p38, JNK,
      and ERK), the focal adhesion kinase (FAK), matrix metalloproteinases (MMPs) and
      NFkappaB. Moreover, MGB1 regulates epithelial to mesenchymal (EMT) features and
      modulates Snail, Twist and ZEB1 expression levels. Interestingly, we also
      observed that expression of MGB1 confers breast cancer cell sensitivity to
      anticancer drug-induced apoptosis. Together, our results support a role for MGB1
      in tumor malignancy in exchange for chemosensitivity. These findings provide one
      of the first descriptive overview of the molecular and cellular roles of MGB1 in
      breast cancer processes and may offer new insight to the development of
      therapeutic and prognostic strategies in breast cancer patients. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26207727
TI  - Trp-Cage Folding on Organic Surfaces.
AB  - Trp-cage is an artificial miniprotein that is small, stable, and fast folding due
      to concerted hydrophobic shielding of a Trp residue by polyproline helices.
      Simulations have extensively characterized Trp-cage; however, the interactions of
      Trp-cage with organic surfaces (e.g., membranes) and their effect on protein
      conformation are largely unknown. To better understand these interactions we
      utilized a combination of replica-exchange molecular dynamics (REMD) and
      metadynamics (MetaD), to investigate Trp-cage folding on self-assembled
      monolayers (SAMs). We found that, with REMD and MetaD, Trp-cage strongly binds to
      neutral CH3 surfaces (-25kT) and moderately adsorbs to anionic COOH interfaces (
      7.6kT), with hydrophobic interactions driving CH3 adhesion and electrostatic
      attractions driving COOH adhesion. Similar to solid-state surfaces, SAMs
      facilitate a number of intermediate Trp-cage conformations between folded and
      unfolded states. Regarding Trp-cage's aromatic groups in neutral CH3 systems, Tyr
      becomes oriented parallel to the surface in order to maximize hydrophobic
      interactions while Trp remains caged perpendicular to the surface; however, Trp
      can reorient itself parallel to the interface as the miniprotein more closely
      binds to the surface. In contrast, Tyr and Trp are both repelled from COOH
      surfaces, though the Trp-cage still adheres to the anionic interface via Lys and
      its N-terminated Asn residue. 

PMID- 26207728
TI  - Fast Anion-Exchange in Highly Luminescent Nanocrystals of Cesium Lead Halide
      Perovskites (CsPbX3, X = Cl, Br, I).
AB  - Postsynthetic chemical transformations of colloidal nanocrystals, such as ion
      exchange reactions, provide an avenue to compositional fine-tuning or to
      otherwise inaccessible materials and morphologies. While cation-exchange is
      facile and commonplace, anion-exchange reactions have not received substantial
      deployment. Here we report fast, low-temperature, deliberately partial, or
      complete anion-exchange in highly luminescent semiconductor nanocrystals of
      cesium lead halide perovskites (CsPbX3, X = Cl, Br, I). By adjusting the halide
      ratios in the colloidal nanocrystal solution, the bright photoluminescence can be
      tuned over the entire visible spectral region (410-700 nm) while maintaining high
      quantum yields of 20-80% and narrow emission line widths of 10-40 nm (from blue
      to red). Furthermore, fast internanocrystal anion-exchange is demonstrated,
      leading to uniform CsPb(Cl/Br)3 or CsPb(Br/I)3 compositions simply by mixing
      CsPbCl3, CsPbBr3, and CsPbI3 nanocrystals in appropriate ratios. 

PMID- 26207729
TI  - Projected carbon stocks in the conterminous USA with land use and variable fire
      regimes.
AB  - The dynamic global vegetation model (DGVM) MC2 was run over the conterminous USA
      at 30 arc sec (~800 m) to simulate the impacts of nine climate futures generated
      by 3GCMs (CSIRO, MIROC and CGCM3) using 3 emission scenarios (A2, A1B and B1) in
      the context of the LandCarbon national carbon sequestration assessment. It first
      simulated potential vegetation dynamics from coast to coast assuming no human
      impacts and naturally occurring wildfires. A moderate effect of increased
      atmospheric CO2 on water use efficiency and growth enhanced carbon sequestration
      but did not greatly influence woody encroachment. The wildfires maintained
      prairie-forest ecotones in the Great Plains. With simulated fire suppression, the
      number and impacts of wildfires was reduced as only catastrophic fires were
      allowed to escape. This greatly increased the expansion of forests and woodlands
      across the western USA and some of the ecotones disappeared. However, when fires
      did occur, their impacts (both extent and biomass consumed) were very large. We
      also evaluated the relative influence of human land use including forest and crop
      harvest by running the DGVM with land use (and fire suppression) and simple land
      management rules. From 2041 through 2060, carbon stocks (live biomass, soil and
      dead biomass) of US terrestrial ecosystems varied between 155 and 162 Pg C across
      the three emission scenarios when potential natural vegetation was simulated.
      With land use, periodic harvest of croplands and timberlands as well as the
      prevention of woody expansion across the West reduced carbon stocks to a range of
      122-126 Pg C, while effective fire suppression reduced fire emissions by about
      50%. Despite the simplicity of our approach, the differences between the size of
      the carbon stocks confirm other reports of the importance of land use on the
      carbon cycle over climate change. 

PMID- 26207730
TI  - Integration of e-Health Tools Into Face-to-Face Psychotherapy for Borderline
      Personality Disorder: A Chance to Close the Gap Between Demand and Supply?
AB  - Borderline personality disorder (BPD) is a severe, highly prevalent mental
      disorder. Effective psychological treatments for BPD are available. However, most
      patients do not receive evidence-based treatments partly because of high
      treatment delivery costs and lack of specialized therapists. By integrating
      specialized e-health tools into BPD-specific treatments, treatment intensity can
      be increased, frequency of face-to-face sessions and burden for psychotherapists
      can be reduced, and implementation of new skills and experiences in the everyday
      life of these patients can be promoted. This bears great potential to increase
      the availability of evidenced-based psychotherapy for BPD patients and close the
      gap between demand and supply. In this article we present such an innovative e
      health tool, priovi, which has been developed for schema therapy. The concept and
      application of priovi are described and illustrated with a case example. 

PMID- 26207731
TI  - Activity antifungal of the essential oils; aqueous and ethanol extracts from
      Citrus aurantium L.
AB  - Our study is about the essential oil of Citrus aurantium L. in Tunisia and its
      plant extract. The yield of this essential oil is 0, 56% but the yield of the
      extract of plant was 17.1% for the aqueous extract ant 18.3% for the ethanolic
      extract. The analysis of chemical composition by using GC and GC/MS showed the
      essential oil of C. aurantium L. species to be rich in monoterpenes such as alpha
      terpineol, lianolyl acetate, linalool and limonene. The antifungal activity of
      this oil showed us an inhibition of the germination of mushrooms, in the same way
      we could note that the biologic activities are generally assigned to the
      chemotypes high content in oxygenated monoterpene. 

PMID- 26207737
TI  - Macrosomic Neonates Carry Increased Risk of Dental Caries in Early Childhood:
      Findings from a Cohort Study, the Okinawa Child Health Study, Japan.
AB  - BACKGROUND: Although many studies have discussed health risks in neonates with a
      low birth weight, few studies have focused on the risks in neonates with a high
      birth weight. The objective of this study was to determine whether differences in
      the incidence of dental caries in early childhood are associated with birth
      weight status. METHODS: A total of 117,175 children born in Okinawa Prefecture,
      Japan from 1997 to 2007 were included in this study. Medical professionals
      collected information about birth records, growth and development, parental child
      rearing practices and dental health at 3 months, 18 months and 3 years of age.
      The risk of dental caries among neonates with macrosomia (birth weight >=4000 g)
      was compared with that among neonates with normal weight (2500-3999 g).
      Sensitivity analyses included 'large for gestational age' (LGA, birth weight
      above the 90th percentile for gestational age), which was relative to
      'appropriate for gestational age' (birth weight between 10th and 90th
      percentiles). Relative risks and relative risk increases were estimated by
      multivariate Poisson regression. RESULTS: At 3 years of age, the relative risk
      increases for dental caries after adjusting for confounding factors were 19% [95%
      confidence interval (CI), 11%-28%, P < 0.001] for macrosomic neonates and 12%
      (95% CI, 9%-16%, P < 0.001) for LGA neonates. CONCLUSION: Macrosomia and LGA were
      associated with an increased risk of dental caries in early childhood. Particular
      attention should be paid to abnormally large neonates.

PMID- 26207738
TI  - Transcriptional Response of Human Neurospheres to Helper-Dependent CAV-2 Vectors
      Involves the Modulation of DNA Damage Response, Microtubule and Centromere Gene
      Groups.
AB  - Brain gene transfer using viral vectors will likely become a therapeutic option
      for several disorders. Helper-dependent (HD) canine adenovirus type 2 vectors
      (CAV-2) are well suited for this goal. These vectors are poorly immunogenic,
      efficiently transduce neurons, are retrogradely transported to afferent
      structures in the brain and lead to long-term transgene expression. CAV-2 vectors
      are being exploited to unravel behavior, cognition, neural networks, axonal
      transport and therapy for orphan diseases. With the goal of better understanding
      and characterizing HD-CAV-2 for brain therapy, we analyzed the transcriptomic
      modulation induced by HD-CAV-2 in human differentiated neurospheres derived from
      midbrain progenitors. This 3D model system mimics several aspects of the dynamic
      nature of human brain. We found that differentiated neurospheres are readily
      transduced by HD-CAV-2 and that transduction generates two main transcriptional
      responses: a DNA damage response and alteration of centromeric and microtubule
      probes. Future investigations on the biochemistry of processes highlighted by
      probe modulations will help defining the implication of HD-CAV-2 and CAR receptor
      binding in enchaining these functional pathways. We suggest here that the
      modulation of DNA damage genes is related to viral DNA, while the alteration of
      centromeric and microtubule probes is possibly enchained by the interaction of
      the HD-CAV-2 fibre with CAR. 

PMID- 26207739
TI  - Spatially Localized Two-Dimensional J-Resolved NMR Spectroscopy via
      Intermolecular Double-Quantum Coherences for Biological Samples at 7 T.
AB  - BACKGROUND AND PURPOSE: Magnetic resonance spectroscopy (MRS) constitutes a
      mainstream technique for characterizing biological samples. Benefiting from the
      separation of chemical shifts and J couplings, spatially localized two
      dimensional (2D) J-resolved spectroscopy (JPRESS) shows better identification of
      complex metabolite resonances than one-dimensional MRS does and facilitates the
      extraction of J coupling information. However, due to variations of macroscopic
      magnetic susceptibility in biological samples, conventional JPRESS spectra
      generally suffer from the influence of field inhomogeneity. In this paper, we
      investigated the implementation of the localized 2D J-resolved spectroscopy based
      on intermolecular double-quantum coherences (iDQCs) on a 7 T MRI scanner.
      MATERIALS AND METHODS: A gamma-aminobutyric acid (GABA) aqueous solution, an
      intact pig brain tissue, and a whole fish (Harpadon nehereus) were explored by
      using the localized iDQC J-resolved spectroscopy (iDQCJRES) method, and the
      results were compared to those obtained by using the conventional 2D JPRESS
      method. RESULTS: Inhomogeneous line broadening, caused by the variations of
      macroscopic magnetic susceptibility in the detected biological samples (the
      intact pig brain tissue and the whole fish), degrades the quality of 2D JPRESS
      spectra, particularly when a large voxel is selected and some strongly structured
      components are included (such as the fish spinal cord). By contrast, high
      resolution 2D J-resolved information satisfactory for metabolite analyses can be
      obtained from localized 2D iDQCJRES spectra without voxel size limitation and
      field shimming. From the contrastive experiments, it is obvious that the spectral
      information observed in the localized iDQCJRES spectra acquired from large voxels
      without field shimming procedure (i.e. in inhomogeneous fields) is similar to
      that provided by the JPRESS spectra acquired from small voxels after field
      shimming procedure (i.e. in relatively homogeneous fields). CONCLUSION: The
      localized iDQCJRES method holds advantage for recovering high-resolution 2D J
      resolved information from inhomogeneous fields caused by external non-ideal field
      condition or internal macroscopic magnetic susceptibility variations in
      biological samples, and it is free of voxel size limitation and time-consuming
      field shimming procedure. This method presents a complementary way to the
      conventional JPRESS method for MRS measurements on MRI systems equipped with
      broad inner bores, and may provide a promising tool for in vivo MRS applications.

PMID- 26207740
TI  - A Methodology for the Development of RESTful Semantic Web Services for Gene
      Expression Analysis.
AB  - Gene expression studies are generally performed through multi-step analysis
      processes, which require the integrated use of a number of analysis tools. In
      order to facilitate tool/data integration, an increasing number of analysis tools
      have been developed as or adapted to semantic web services. In recent years, some
      approaches have been defined for the development and semantic annotation of web
      services created from legacy software tools, but these approaches still present
      many limitations. In addition, to the best of our knowledge, no suitable approach
      has been defined for the functional genomics domain. Therefore, this paper aims
      at defining an integrated methodology for the implementation of RESTful semantic
      web services created from gene expression analysis tools and the semantic
      annotation of such services. We have applied our methodology to the development
      of a number of services to support the analysis of different types of gene
      expression data, including microarray and RNASeq. All developed services are
      publicly available in the Gene Expression Analysis Services (GEAS) Repository at
      http://dcm.ffclrp.usp.br/lssb/geas. Additionally, we have used a number of the
      developed services to create different integrated analysis scenarios to reproduce
      parts of two gene expression studies documented in the literature. The first
      study involves the analysis of one-color microarray data obtained from multiple
      sclerosis patients and healthy donors. The second study comprises the analysis of
      RNA-Seq data obtained from melanoma cells to investigate the role of the
      remodeller BRG1 in the proliferation and morphology of these cells. Our
      methodology provides concrete guidelines and technical details in order to
      facilitate the systematic development of semantic web services. Moreover, it
      encourages the development and reuse of these services for the creation of
      semantically integrated solutions for gene expression analysis. 

PMID- 26207741
TI  - Correction: In Vitro Activity of Rifampicin and Verapamil Combination in
      Multidrug-Resistant Mycobacterium tuberculosis.

PMID- 26207742
TI  - Fully Flexible Docking of Medium Sized Ligand Libraries with RosettaLigand.
AB  - RosettaLigand has been successfully used to predict binding poses in protein
      small molecule complexes. However, the RosettaLigand docking protocol is
      comparatively slow in identifying an initial starting pose for the small molecule
      (ligand) making it unfeasible for use in virtual High Throughput Screening
      (vHTS). To overcome this limitation, we developed a new sampling approach for
      placing the ligand in the protein binding site during the initial 'low
      resolution' docking step. It combines the translational and rotational
      adjustments to the ligand pose in a single transformation step. The new algorithm
      is both more accurate and more time-efficient. The docking success rate is
      improved by 10-15% in a benchmark set of 43 protein/ligand complexes, reducing
      the number of models that typically need to be generated from 1000 to 150. The
      average time to generate a model is reduced from 50 seconds to 10 seconds. As a
      result we observe an effective 30-fold speed increase, making RosettaLigand
      appropriate for docking medium sized ligand libraries. We demonstrate that this
      improved initial placement of the ligand is critical for successful prediction of
      an accurate binding position in the 'high-resolution' full atom refinement step. 

PMID- 26207743
TI  - Differences in Copper Absorption and Accumulation between Copper-Exclusion and
      Copper-Enrichment Plants: A Comparison of Structure and Physiological Responses.
AB  - Differences in copper (Cu) absorption and transport, physiological responses and
      structural characteristics between two types of Cu-resistant plants, Oenothera
      glazioviana (Cu-exclusion type) and Elsholtzia haichowensis (Cu-enrichment type),
      were investigated in the present study. The results indicated the following: (1)
      After 50 MUM Cu treatment, the Cu ratio in the xylem vessels of E. haichowensis
      increased by 60%. A Cu adsorption experiment indicated that O. glazioviana
      exhibited greater resistance to Cu, and Cu absorption and the shoot/root ratio of
      Cu were significantly lower in O. glazioviana than in E. haichowensis. (2) An
      analysis of the endogenous abscisic acid (ABA) variance and exogenous ABA
      treatment demonstrated that the ABA levels of both plants did not differ;
      exogenous ABA treatment clearly reduced Cu accumulation in both plants. (3) The
      leaf stomatal density of O. glazioviana was significantly less than that of E.
      haichowensis. Guard cells in E. haichowensis plants were covered with a thick
      cuticle layer, the epidermal hair was more numerous and longer, and the number of
      xylem conduits in the root was small. (4) The transpiration rate and the stomatal
      conductance of O. glazioviana were both significantly lower than those of E.
      haichowensis, regardless of whether the plants were treated with Cu. Taken
      together, these results indicate that the differences in the structural
      characteristics between these two plant species, particularly in the
      characteristics related to plant transpiration, are important factors that govern
      whether plants acquire or exclude Cu. 

PMID- 26207744
TI  - Age and Gender Differences in Urinary Levels of Eleven Phthalate Metabolites in
      General Taiwanese Population after a DEHP Episode.
AB  - INTRODUCTION: In 2011, the Taiwan FDA disclosed illegal di(2-ethylhexyl
      phthalate) (DEHP) and dibutyl phthalate (DBP) use in beverage and nutrition
      supplements. We aim to determine phthalate exposure and other relevant factors in
      a sample of the general Taiwanese population in order to evaluate actual
      phthalate exposure levels after this disclosure of DEHP use. METHOD: We selected
      subjects aged 7 years old and older in 2013 from the general Taiwanese
      population. First morning urine samples from each participant were collected to
      analyze 11 phthalate metabolites representing 7 parent phthalates using on-line
      liquid chromatography/ tandem mass spectrometry. An interview questionnaire was
      applied to obtain participant demographic characteristics, lifestyle, and other
      relevant factors. RESULTS: The median levels of metabolites of DEHP, including
      mono-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP),
      mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl)
      phthalate (MECPP), DBP (DnBP and DiBP), including mono-n-butyl phthalate (MnBP)
      and mono-iso-butyl phthalate (MiBP), and mono-ethyl phthalate (MEP) in urine
      samples of 290 adults/ 97 minors (<18 years) were 7.9/ 6.1, 12.6/ 17.8, 22.0/
      25.8, 25.4/ 30.8, 18.1/ 23.6, 9.4/ 13.6 and 14.5/ 12.4 MUg/g creatinine,
      respectively. Women (?18 years) were exposed to significantly higher levels of
      MEHHP (P=0.011), MECPP (P=0.01), MnBP (P=0.001) and MEP (P<0.001) than men (?18
      years), whereas no gender difference was observed in minors. We found significant
      higher level of MEP (creatinine-unadjusted) in subject aged between 18 to 40
      years old (P<0.001), especially for women. Exposure levels of MEOHP (P<0.001),
      MECPP (P=0.002) and MnBP (P=0.044) in minors were significantly higher than those
      of adults. High frequency usage of food preservation film and bags, and personal
      care products are potential sources of phthalates exposure in general Taiwanese.
      CONCLUSION: Our findings indicated that DEHP and DBP exposure in a sample of the
      general Taiwanese population varied by age and gender, possibly affected by
      different lifestyles, and continuing bio-monitoring surveillance is warranted.

PMID- 26207745
TI  - Permeation of Dopamine Sulfate through the Blood-Brain Barrier.
AB  - Dopamine sulfate (DA-3- and DA-4-S) have been determined in the human brain, but
      it is unclear whether they are locally formed in the central nervous system
      (CNS), or transported into the CNS from peripheral sources. In the current study,
      permeation of the blood-brain barrier (BBB) by DA-S was studied by injecting 13C6
      labelled regioisomers of DA-S (13DA-3-S and 13DA-4-S) and dopamine (DA)
      subcutaneously (s.c.) in anesthetized rats, then analyzing brain microdialysis
      and plasma samples by UPLC-MS/MS. The results in the microdialysis samples
      demonstrated that brain concentrations of 13DA-S regioisomers clearly increased
      after the s.c. injections. The concentration of DA did not change, indicating the
      permeation of DA-S through an intact BBB. The analysis of plasma samples,
      however, showed that DA-S only permeates the BBB to a small extent, as the
      concentrations in plasma were substantially higher than in the microdialysis
      samples. The results also showed that the concentrations of DA-3-S were around
      three times higher than the concentrations of DA-4-S in rat brain, as well as in
      the plasma samples after the s.c. injections, indicating that DA-3-S and DA-4-S
      permeate the BBB with similar efficiency. The fate of 13DA-S in brain was
      followed by monitoring 13C6-labelled DA-S hydrolysis products, i.e. 13DA and its
      common metabolites; however, no 13C6-labelled products were detected. This
      suggests that DA-S either permeates through the BBB back to the peripheral
      circulation or is dissociated or metabolized by unexpected mechanisms. 

PMID- 26207746
TI  - Discovery of NCT-501, a Potent and Selective Theophylline-Based Inhibitor of
      Aldehyde Dehydrogenase 1A1 (ALDH1A1).
AB  - Aldehyde dehydrogenases (ALDHs) metabolize reactive aldehydes and possess
      important physiological and toxicological functions in areas such as CNS,
      metabolic disorders, and cancers. Increased ALDH (e.g., ALDH1A1) gene expression
      and catalytic activity are vital biomarkers in a number of malignancies and
      cancer stem cells, highlighting the need for the identification and development
      of small molecule ALDH inhibitors. A new series of theophylline-based analogs as
      potent ALDH1A1 inhibitors is described. The optimization of hits identified from
      a quantitative high throughput screening (qHTS) campaign led to analogs with
      improved potency and early ADME properties. This chemotype exhibits highly
      selective inhibition against ALDH1A1 over ALDH3A1, ALDH1B1, and ALDH2 isozymes as
      well as other dehydrogenases such as HPGD and HSD17beta4. Moreover, the
      pharmacokinetic evaluation of selected analog 64 (NCT-501) is also highlighted. 

PMID- 26207750
TI  - Lower Serum Creatinine Is Associated with Low Bone Mineral Density in Subjects
      without Overt Nephropathy.
AB  - BACKGROUND: Low skeletal muscle mass is associated with deterioration of bone
      mineral density. Because serum creatinine can serve as a marker of muscle mass,
      we evaluated the relationship between serum creatinine and bone mineral density
      in an older population with normal renal function. METHODS: Data from a total of
      8,648 participants (4,573 men and 4,075 postmenopausal women) aged 45-95 years
      with an estimated glomerular filtration rate >60 ml/min/1.73 m2 were analyzed
      from the Fourth Korea National Health and Nutrition Examination Survey (2008
      2010). Bone mineral density (BMD) and appendicular muscle mass (ASM) were
      measured using dual-energy X-ray absorptiometry. Receiver operating
      characteristic curve analysis revealed that the cut points of serum creatinine
      for sarcopenia were below 0.88 mg/dl in men and 0.75 mg/dl in women. Subjects
      were divided into two groups: low creatinine and upper normal creatinine
      according to the cut point value of serum creatinine for sarcopenia. RESULTS: In
      partial correlation analysis adjusted for age, serum creatinine was positively
      associated with both BMD and ASM. Subjects with low serum creatinine were at a
      higher risk for low BMD (T-score <= -1.0) at the femur neck, total hip and lumbar
      spine in men, and at the total hip and lumbar spine in women after adjustment for
      confounding factors. Each standard deviation increase in serum creatinine was
      significantly associated with reduction in the likelihood of low BMD at the total
      hip and lumbar spine in both sexes (men: odds ratio (OR) = 0.84 [95% CI = 0.74
      0.96] at the total hip, OR = 0.8 [95% CI = 0.68-0.96] at the lumbar spine; women:
      OR = 0.83 [95% CI = 0.73-0.95] at the total hip, OR=0.81 [95% CI = 0.67-0.99] at
      the lumbar spine). CONCLUSIONS: Serum creatinine reflected muscle mass, and low
      serum creatinine was independently associated with low bone mineral density in
      subjects with normal kidney function.

PMID- 26207752
TI  - On the origin of spontaneous activity in the bladder.
AB  - OBJECTIVES: To characterise separately the pharmacological profiles of
      spontaneous contractions from the mucosa and detrusor layers of the bladder wall
      and to describe the relationship in mucosa between adenosine triphosphate (ATP)
      release and spontaneous contractions. MATERIALS AND METHODS: Spontaneous
      contractions were measured (36  degrees C) from isolated mucosa or detrusor
      preparations, and intact (mucosa + detrusor) preparations from guinea-pig
      bladders. Potential modulators were added to the superfusate. The percentage of
      smooth muscle was measured in haematoxylin and eosin stained sections. ATP
      release was measured in superfusate samples from a fixed point above the
      preparation using a luciferin-luciferase assay. RESULTS: The magnitude of
      spontaneous contractions was in the order intact >mucosa >detrusor. The
      percentage of smooth muscle was least in mucosa and greatest in detrusor
      preparations. The pharmacological profiles of spontaneous contractions were
      different in mucosa and detrusor in response to P2X or P2Y receptor agonists,
      adenosine and capsaicin. The intact preparations showed responses intermediate to
      those from mucosa and detrusor preparations. Low extracellular pH generated large
      changes in detrusor, but not mucosa preparations. The mucosa preparations
      released ATP in a cyclical manner, followed by variations in spontaneous
      contractions. ATP release was greater in mucosa compared with detrusor, augmented
      by carbachol and reversed by the M2 -selective antagonist, methoctramine.
      CONCLUSIONS: The different pharmacological profiles of bladder mucosa and
      detrusor, implies different pathways for contractile activation. Also, the
      intermediate responses from intact preparations implies functional interaction.
      The temporal relationship between cyclical variation of ATP release and amplitude
      of spontaneous contractions is consistent with ATP release controlling
      spontaneous activity. Carbachol-mediated ATP release was independent of active
      contractile force.

PMID- 26207751
TI  - Citrus tristeza virus (CTV) Causing Proteomic and Enzymatic Changes in Sweet
      Orange Variety "Westin".
AB  - Citrus Tristeza disease, caused by CTV (Citrus tristeza virus), committs citrus
      plantations around the world and specifically attacks phloem tissues of the
      plant. The virus exists as a mixture of more or less severe variants, which may
      or may not cause symptoms of Tristeza. The objective of this study was to analyze
      the changes caused by CTV in the proteome of stems of sweet orange, as well as in
      the activity and gene expression of antioxidant enzymes. The CTV-infected sweet
      orange displayed mild symptoms, which were characterized by the presence of
      sparse stem pitting throughout their stems. The presence of virus was confirmed
      by RT-PCR. Proteomic analysis by 2DE-PAGE-MS / MS revealed the identity of 40
      proteins differentially expressed between CTV- infected and -non-infected
      samples. Of these, 33 were up-regulated and 7 were down-regulated in CTV-infected
      samples. Among the proteins identified stands out a specific from the virus, the
      coat protein. Other proteins identified are involved with oxidative stress and
      for this their enzymatic activity was measured. The activity of superoxide
      dismutase (SOD) was higher in CTV-infected samples, as catalase (CAT) showed
      higher activity in uninfected samples. The activity of guaiacol peroxidase (GPX)
      did not vary significantly between samples. However, ascorbate peroxidase (APX)
      was more active in the infected samples. The relative expression of the genes
      encoding CAT, SOD, APX and GPX was analyzed by quantitative real time PCR (RT
      qPCR). The CTV-infected samples showed greater accumulation of transcripts,
      except for the CAT gene. This gene showed higher expression in the uninfected
      samples. Taken together, it can be concluded that the CTV affects the protein
      profile and activity and gene expression of antioxidant enzymes in plants
      infected by this virus. 

PMID- 26207753
TI  - A Genomic, Transcriptomic and Proteomic Look at the GE2270 Producer Planobispora
      rosea, an Uncommon Actinomycete.
AB  - We report the genome sequence of Planobispora rosea ATCC 53733, a mycelium
      forming soil-dweller belonging to one of the lesser studied genera of
      Actinobacteria and producing the thiopeptide GE2270. The P. rosea genome presents
      considerable convergence in gene organization and function with other members in
      the family Streptosporangiaceae, with a significant number (44%) of shared
      orthologs. Patterns of gene expression in P. rosea cultures during exponential
      and stationary phase have been analyzed using whole transcriptome shotgun
      sequencing and by proteome analysis. Among the differentially abundant proteins,
      those involved in protein metabolism are particularly represented, including the
      GE2270-insensitive EF-Tu. Two proteins from the pbt cluster, directing GE2270
      biosynthesis, slightly increase their abundance values over time. While GE2270
      production starts during the exponential phase, most pbt genes, as analyzed by
      qRT-PCR, are down-regulated. The exception is represented by pbtA, encoding the
      precursor peptide of the ribosomally synthesized GE2270, whose expression reached
      the highest level at the entry into stationary phase. 

PMID- 26207754
TI  - First Neuromuscular Contact Correlates with Onset of Primary Myogenesis in Rat
      and Mouse Limb Muscles.
AB  - Skeletal muscle development has been the focus of intensive study for many
      decades. Recent advances in genetic manipulation of the mouse have increased our
      understanding of the cell signalling involved in the development of muscle
      progenitors which give rise to adult skeletal muscles and their stem cell
      populations. However, the influence of a vital tissue type - the peripheral nerve
      has largely been ignored since its earliest descriptions. Here we carefully
      describe the timing in which myogenic progenitors expressing Pax3 and Pax7 (the
      earliest markers of myogenic cells) enter the limb buds of rat and mouse embryos,
      as well as the spatiotemporal relationship between these progenitors and the
      ingrowing peripheral nerve. We show that progenitors expressing Pax3 enter the
      limb bud one full day ahead of the first neurites and that Pax7-expressing
      progenitors (associated with secondary myogenesis in the limb) are first seen in
      the limb bud at the time of nerve entry and in close proximity to the nerve. The
      initial entry of the nerve also coincides with the first expression of myosin
      heavy chain showing that the first contact between nerves and myogenic cells
      correlates with the onset of myogenic differentiation. Furthermore, as the nerve
      grows into the limb, Pax3 expression is progressively replaced by Pax7 expression
      in myogenic progenitors. These findings indicate that the ingrowing nerve enters
      the limb presumptive muscle masses earlier than what was generally described and
      raises the possibility that nerve may influence the differentiation of muscle
      progenitors in rodent limbs. 

PMID- 26207755
TI  - Effect of Handrail Height on Sit-To-Stand Movement.
AB  - BACKGROUND: Care-needing older adults and disabled individuals often require
      handrails for assistance of movements, such as sit-to-stand movements. Handrails
      must be set at the appropriate position; however, the effects of handrail height
      on joint movement and center-of-gravity movements during sit-to-stand movement
      remain unclear. In the present study, we sought to clarify the effects of
      handrail height on joint movement, center-of-gravity, and floor reaction force
      during sit-to-stand movement. METHODS: Subjects included 16 healthy young adults
      and 25 older adults who require long-term care. Kinetic and kinematic
      measurements during sit-to-stand movement of young adults were conducted using a
      3-D motion analyzer and a force plate. Trunk forward tilt angle during sit-to
      stand movement of older adults was measured using a still image from a video
      recording. RESULTS: Using low handrails, sit-to-stand movement resulted in an
      increased hip flexion angle, ankle dorsiflexion angle, and trunk forward tilt
      angle and a greater forward center-of-gravity shift than when not using handrails
      in young adults during seat-off. In contrast, using high handrails resulted in a
      smaller hip flexion angle and trunk forward tilt angle in young adults. The
      backward force on the floor was decreased in the low handrail condition, and was
      increased in the high handrail condition rather than that of sit-to-stand
      movement without handrails in young adults. The effect of handrail height on
      trunk forward tilt angle was the same in both healthy young adults and care
      needing older adults during seat-off. CONCLUSION: Because handrail height affects
      joint movement and shift in the center-of-gravity during sit-to-stand movement,
      handrail position should be selected to match the status of older adults with
      functional impairment.

PMID- 26207757
TI  - Response of Surface Soil Hydrology to the Micro-Pattern of Bio-Crust in a Dry
      Land Loess Environment, China.
AB  - The specific bio-species and their spatial patterns play crucial roles in
      regulating eco-hydrologic process, which is significant for large-scale habitat
      promotion and vegetation restoration in many dry-land ecosystems. Such effects,
      however, are not yet fully studied. In this study, 12 micro-plots, each with size
      of 0.5 m in depth and 1 m in length, were constructed on a gentle grassy hill
      slope with a mean gradient of 8 degrees  in a semiarid loess hilly area of China.
      Two major bio-crusts, including mosses and lichens, had been cultivated for two
      years prior to the field simulation experiments, while physical crusts and non
      crusted bare soils were used for comparison. By using rainfall simulation method,
      four designed micro-patterns (i.e., upper bio-crust and lower bare soil,
      scattered bio-crust, upper bare soil and lower bio-crust, fully-covered bio
      crust) to the soil hydrological response were analyzed. We found that soil
      surface bio-crusts were more efficient in improving soil structure, water holding
      capacity and runoff retention particularly at surface 10 cm layers, compared with
      physical soil crusts and non-crusted bare soils. We re-confirmed that mosses
      functioned better than lichens, partly due to their higher successional stage and
      deeper biomass accumulation. Physical crusts were least efficient in water
      conservation and erosion control, followed by non-crusted bare soils. More
      importantly, there were marked differences in the efficiency of the different
      spatial arrangements of bio-crusts in controlling runoff and sediment generation.
      Fully-covered bio-crust pattern provides the best option for soil loss reduction
      and runoff retention, while a combination of upper bio-crust and lower bare soil
      pattern is the least one. These findings are suggested to be significant for
      surface-cover protection, rainwater infiltration, runoff retention, and erosion
      control in water-restricted and degraded natural slopes. 

PMID- 26207756
TI  - Novel Apo E-Derived ABCA1 Agonist Peptide (CS-6253) Promotes Reverse Cholesterol
      Transport and Induces Formation of prebeta-1 HDL In Vitro.
AB  - Apolipoprotein (apo) mimetic peptides replicate some aspects of HDL function. We
      have previously reported the effects of compound ATI-5261 on its ability to
      replicate many functions of native apo A-I in the process of HDL biogenesis. ATI
      5261 induced muscle toxicity in wild type C57Bl/6 mice, increased CPK, ALT and
      AST and increase in triglyceride (Tg) levels. Aromatic phenylalanine residues on
      the non-polar face of ATI-5261, together with positively charged arginine
      residues at the lipid-water interface were responsible for these effects. This
      information was used to create a novel analog (CS-6253) that was non-toxic. We
      evaluated this peptide designed from the carboxyl terminus of apo E, in its
      ability to mimic apo A-I functionality. Our data shows that the lipidated
      particles generated by incubating cells overexpressing ABCA1 with lipid free CS
      6253 enhances the rate of ABCA1 lipid efflux with high affinity interactions with
      native ABCA1 oligomeric forms and plasma membrane micro-domains. Interaction
      between ABCA1 and lipid free CS-6253 resulted in formation of nascent HDL-CS-6253
      particles that are actively remodeled in plasma. Mature HDL-CS-6253 particles
      deliver cholesterol to liver cells via SR-BI in-vitro. CS-6253 significantly
      increases cholesterol efflux in murine macrophages and in human THP-1 macrophage
      derived foam cells expressing ABCA1. Addition of CS-6253 to plasma dose
      dependently displaced apo A-I from alpha-HDL particles and led to de novo
      formation of prebeta-1 HDL that stimulates ABCA1 dependent cholesterol efflux
      efficiently. When incubated with human plasma CS-6253 was also found to bind with
      HDL and LDL and promoted the transfer of cholesterol from HDL to LDL
      predominantly. Our data shows that CS-6253 mimics apo A-I in its ability to
      promote ABCA1-mediated formation of nascent HDL particles, and enhances formation
      of prebeta-1 HDL with increase in the cycling of apo A-I between the prebeta and
      alpha-HDL particles in-vitro. These mechanisms are potentially anti-atherogenic. 

PMID- 26207759
TI  - Sizing the Problem of Improving Discovery and Access to NIH-Funded Data: A
      Preliminary Study.
AB  - OBJECTIVE: This study informs efforts to improve the discoverability of and
      access to biomedical datasets by providing a preliminary estimate of the number
      and type of datasets generated annually by research funded by the U.S. National
      Institutes of Health (NIH). It focuses on those datasets that are "invisible" or
      not deposited in a known repository. METHODS: We analyzed NIH-funded journal
      articles that were published in 2011, cited in PubMed and deposited in PubMed
      Central (PMC) to identify those that indicate data were submitted to a known
      repository. After excluding those articles, we analyzed a random sample of the
      remaining articles to estimate how many and what types of invisible datasets were
      used in each article. RESULTS: About 12% of the articles explicitly mention
      deposition of datasets in recognized repositories, leaving 88% that are invisible
      datasets. Among articles with invisible datasets, we found an average of 2.9 to
      3.4 datasets, suggesting there were approximately 200,000 to 235,000 invisible
      datasets generated from NIH-funded research published in 2011. Approximately 87%
      of the invisible datasets consist of data newly collected for the research
      reported; 13% reflect reuse of existing data. More than 50% of the datasets were
      derived from live human or non-human animal subjects. CONCLUSION: In addition to
      providing a rough estimate of the total number of datasets produced per year by
      NIH-funded researchers, this study identifies additional issues that must be
      addressed to improve the discoverability of and access to biomedical research
      data: the definition of a "dataset," determination of which (if any) data are
      valuable for archiving and preservation, and better methods for estimating the
      number of datasets of interest. Lack of consensus amongst annotators about the
      number of datasets in a given article reinforces the need for a principled way of
      thinking about how to identify and characterize biomedical datasets.

PMID- 26207758
TI  - School-Age Children Are a Reservoir of Malaria Infection in Malawi.
AB  - Malaria surveillance and interventions in endemic countries often target young
      children at highest risk of malaria morbidity and mortality. We aimed to
      determine whether school-age children and adults not captured in surveillance
      serve as a reservoir for malaria infection and may contribute to malaria
      transmission. Cross-sectional surveys were conducted in one rainy and one dry
      season in southern Malawi. Demographic and health information was collected for
      all household members. Blood samples were obtained for microscopic and PCR
      identification of Plasmodium falciparum. Among 5796 individuals aged greater than
      six months, PCR prevalence of malaria infection was 5%, 10%, and 20% in dry, and
      9%, 15%, and 32% in rainy seasons in Blantyre, Thyolo, and Chikhwawa,
      respectively. Over 88% of those infected were asymptomatic. Participants aged 6
      15 years were at higher risk of infection (OR=4.8; 95%CI, 4.0-5.8) and
      asymptomatic infection (OR=4.2; 95%CI, 2.7-6.6) than younger children in all
      settings. School-age children used bednets less frequently than other age groups.
      Compared to young children, school-age children were brought less often for
      treatment and more often to unreliable treatment sources. CONCLUSION: School-age
      children represent an underappreciated reservoir of malaria infection and have
      less exposure to antimalarial interventions. Malaria control and elimination
      strategies may need to expand to include this age group.

PMID- 26207761
TI  - Synthesis and Evaluation of a Series of Oleanolic Acid Saponins as alpha
      Glucosidase and alpha-Amylase Inhibitors.
AB  - Sixteen naturally occurring oleanolic acid saponins and their derivatives were
      synthesized in an efficient and practical strategy, and their inhibitory
      activities against alpha-glucosidase and alpha-amylase were evaluated in vitro.
      Among all the compounds, 28-O-monoglucoside 8 exhibited remarkably potent
      inhibitory activity against alpha-glucosidase with an IC50 value of 87.3 uM,
      which was fivefold stronger than that of the antidiabetic acarbose. Based on the
      preliminary structure-activity relationships, for 28-O-monoglucosides, the
      presence of a terminal alpha-l-rhamnopyranosyl residue enhanced the alpha
      glucosidase and alpha-amylase inhibitory activities. Furthermore, for 3,28-O
      bidesmosides, sugar-substituted moieties attached to the C-3 and C-28 positions
      of the oleanolic acid scaffold are helpful to increase the inhibitory activities
      against alpha-amylase and alpha-glucosidase.

PMID- 26207760
TI  - Diagnostic Algorithm for Glycogenoses and Myoadenylate Deaminase Deficiency Based
      on Exercise Testing Parameters: A Prospective Study.
AB  - AIM: Our aim was to evaluate the accuracy of aerobic exercise testing to diagnose
      metabolic myopathies. METHODS: From December 2008 to September 2012, all the
      consecutive patients that underwent both metabolic exercise testing and a muscle
      biopsy were prospectively enrolled. Subjects performed an incremental and maximal
      exercise testing on a cycle ergometer. Lactate, pyruvate, and ammonia
      concentrations were determined from venous blood samples drawn at rest, during
      exercise (50% predicted maximal power, peak exercise), and recovery (2, 5, 10,
      and 15 min). Biopsies from vastus lateralis or deltoid muscles were analysed
      using standard techniques (reference test). Myoadenylate deaminase (MAD) activity
      was determined using p-nitro blue tetrazolium staining in muscle cryostat
      sections. Glycogen storage was assessed using periodic acid-Schiff staining. The
      diagnostic accuracy of plasma metabolite levels to identify absent and decreased
      MAD activity was assessed using Receiver Operating Characteristic (ROC) curve
      analysis. RESULTS: The study involved 51 patients. Omitting patients with
      glycogenoses (n = 3), MAD staining was absent in 5, decreased in 6, and normal in
      37 subjects. Lactate/pyruvate at the 10th minute of recovery provided the
      greatest area under the ROC curves (AUC, 0.893 +/- 0.067) to differentiate
      Abnormal from Normal MAD activity. The lactate/rest ratio at the 10th minute of
      recovery from exercise displayed the best AUC (1.0) for discriminating between
      Decreased and Absent MAD activities. The resulting decision tree achieved a
      diagnostic accuracy of 86.3%. CONCLUSION: The present algorithm provides a non
      invasive test to accurately predict absent and decreased MAD activity,
      facilitating the selection of patients for muscle biopsy and target appropriate
      histochemical analysis.

PMID- 26207763
TI  - The impact of social factors on outcomes in patients with bleeding disorders.
AB  - INTRODUCTION: In haemophilia, clinical outcomes are mainly determined by the
      severity of clotting factor deficiency, treatment regimen, availability of
      clotting factor concentrate and age. Information about the relevance of patient
      related factors such as education, social status or impact of the disease on the
      patient's life is scarce. AIM: To assess the impact of social status and disease
      related impairment of certain aspects of the patient's life on clinical and
      psychosocial outcomes in patients with inherited bleeding disorders (PWBD).
      METHODS: Consecutive patients of a single centre were assessed by questionnaires
      on social status and quality of life (SF-36). Social status was defined by school
      and professional education, employment and financial income of patients as well
      as school education of their parents. RESULTS: Fifty-seven PWBD (mean age, 38 +/-
      16 years) were enrolled, 60% were treated on-demand; PWBD had a median number of
      2.5 (0-34) annual bleeds and a median orthopaedic joint score of 6 (0-38). No
      significant differences were found for clinical and psychosocial outcomes across
      social status groups. More than half of the patients reported that haemophilia
      had an impact on their school education, childhood and leisure activities.
      Patients with a high impact of haemophilia on their lives were less satisfied
      with their lives (P < 0.002), reported worse quality of life in all domains of
      the SF-36, had a worse joint score (P < 0.024) and reported more pain (P <
      0.013). CONCLUSION: The perceived impact of haemophilia on patients' lives seems
      to have a stronger impact on clinical and psychosocial outcomes than patients'
      actual social status.

PMID- 26207762
TI  - Functional Characterization of the Mannitol Promoter of Pseudomonas fluorescens
      DSM 50106 and Its Application for a Mannitol-Inducible Expression System for
      Pseudomonas putida KT2440.
AB  - A new pBBR1MCS-2-derived vector containing the Pseudomonas fluorescens DSM10506
      mannitol promoter PmtlE and mtlR encoding its AraC/XylS type transcriptional
      activator was constructed and optimized for low basal expression. Mannitol,
      arabitol, and glucitol-inducible gene expression was demonstrated with
      Pseudomonas putida and eGFP as reporter gene. The new vector was applied for
      functional characterization of PmtlE. Identification of the DNA binding site of
      MtlR was achieved by in vivo eGFP measurement with PmtlE wild type and mutants
      thereof. Moreover, purified MtlR was applied for detailed in vitro investigations
      using electrophoretic mobility shift assays and DNaseI footprinting experiments.
      The obtained data suggest that MtlR binds to PmtlE as a dimer. The proposed DNA
      binding site of MtlR is AGTGC-N5-AGTAT-N7-AGTGC-N5-AGGAT. The transcription
      activation mechanism includes two binding sites with different binding
      affinities, a strong upstream binding site and a weaker downstream binding site.
      The presence of the weak downstream binding site was shown to be necessary to
      sustain mannitol-inducibility of PmtlE. Two possible functions of mannitol are
      discussed; the effector might stabilize binding of the second monomer to the
      downstream half site or promote transcription activation by inducing a
      conformational change of the regulator that influences the contact to the RNA
      polymerase. 

PMID- 26207764
TI  - Wild Blueberry (Vaccinium angustifolium Ait.) Polyphenols Target Fusobacterium
      nucleatum and the Host Inflammatory Response: Potential Innovative Molecules for
      Treating Periodontal Diseases.
AB  - Blueberries contain significant amounts of flavonoids to which a number of
      beneficial health effects in humans have been associated. The present study
      investigated the effect of a polyphenol-rich lowbush blueberry (Vaccinium
      angustifolium Ait.) extract on the two main etiologic components of
      periodontitis, a multifactorial disorder affecting the supporting structures of
      the teeth. Phenolic acids, flavonoids (flavonols, anthocyanins, flavan-3-ols),
      and procyanidins made up 16.6, 12.9, and 2.7% of the blueberry extract,
      respectively. The blueberry extract showed antibacterial activity (MIC = 1 mg/mL)
      against the periodontopathogenic bacterium Fusobacterium nucleatum. This property
      may result from the ability of blueberry polyphenols to chelate iron. Moreover,
      the blueberry extract at 62.5 MUg/mL inhibited F. nucleatum biofilm formation by
      87.5 +/- 2.3%. Subsequently, the ability of the blueberry extract to inhibit the
      NF-kappaB signaling pathway in U937-3xkappaB cells was investigated. The
      blueberry extract dose-dependently inhibited the activation of NF-kappaB induced
      by F. nucleatum. In addition, a pretreatment of macrophages with the blueberry
      extract (62.5 MUg/mL) inhibited the secretion of IL-1beta, TNF-alpha, and IL-6 by
      87.3 +/- 1.3, 80.7 +/- 5.6, and 28.2 +/- 9.3%, respectively, following a
      stimulation with F. nucleatum. Similarly, the secretion of MMP-8 and MMP-9 was
      also dose-dependently inhibited. This dual antibacterial and anti-inflammatory
      action of lowbush blueberry polyphenols suggests that they may be promising
      candidates for novel therapeutic agents. 

PMID- 26207765
TI  - Decision Tree Identified Risk Groups with High Suicidal Ideation in South Korea:
      A Population-Based Study.
AB  - OBJECTIVE: The aim of this study was to identify risk groups with high suicidal
      ideation among South Korean adults. DESIGN AND SAMPLE: A descriptive cross
      sectional design was adopted using secondary data from the 2011 Korea National
      Health and Nutrition Examination Survey (KNHANES). A total of 5,963 adults aged
      19 years and older who participated in the 2011 KNHANES served as participants.
      MEASURES: The prevalence of suicidal ideation and its related factors, including
      physical, psychological, health behavioral, and sociodemographic characteristics,
      were examined. Descriptive statistics and a decision tree were used for data
      analysis. RESULTS: Nine groups with high suicidal ideation were identified. The
      coexistence of depression and high levels of stress increased the prevalence of
      suicidal ideation. The highest risk group was widowed or divorced adults with
      depression and high levels of stress, and 82.5% of these participants had
      suicidal ideation (the prevalence rate of this group was 5.7 times higher than
      the mean suicidal ideation prevalence rate in this study). CONCLUSION: Public
      health nurses and community mental health professionals should recognize risk
      groups with high suicidal ideation, and target these groups when implementing
      preventive interventions.

PMID- 26207766
TI  - Identification of Ethanol and 4-Nitroquinoline-1-Oxide Induced Epigenetic and
      Oxidative Stress Markers During Oral Cavity Carcinogenesis.
AB  - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a cancer that is
      characterized by its high morbidity and mortality rates. While tobacco use and
      alcohol consumption are 2 major contributing factors for HNSCC carcinogenesis,
      how the combination of tobacco and alcohol increases HNSCC risk is not
      understood. METHODS: We combined the 4-nitroquinoline-1-oxide (4-NQO) oral
      carcinogenesis and Meadows-Cook alcohol mouse models to elucidate the molecular
      events and to identify the novel biomarkers associated with oral cancer
      development. RESULTS: By genome-wide RNA-seq of tongue samples (3 mice per
      group), we identified changes in transcripts that mediate alcohol metabolism and
      oxidative stress (Aldh2, Aldh1a3, Adh1, Adh7, and Cyp2a5) in mice treated with 4
      NQO followed by ethanol (4-NQO/EtOH) as compared to the vehicle control/untreated
      (V.C./Untr.) samples. We measured major, global increases in specific histone
      acetylation and methylation epigenetic marks (H3K27ac, H3K9/14ac, H3K27me3, and
      H3K9me3) in the oral cavities of V.C./EtOH, 4-NQO/Untr., and 4-NQO/EtOH treatment
      groups compared to the V.C./Untr. group. We detected changes in histone
      epigenetic marks near regulatory regions of genes involved in ethanol metabolism
      by chromatin immunoprecipitation. For instance, the Aldh2 promoter showed
      increased H3K27me3 marks, and Aldh2 mRNA levels were reduced by 10-fold in
      4NQO/EtOH versus V.C./Untr. tongue samples. 4-NQO/EtOH treatment also caused
      increases in markers of oxidative stress, including 4-HNE, MCT4/SLC16a3, and
      TOM20, as measured by immunohistochemistry. CONCLUSIONS: We delineate a mechanism
      by which 4-NQO and ethanol can regulate gene expression during the development of
      HNSCC and suggest that histone epigenetic marks and oxidative stress markers
      could be the novel biomarkers and targets for the prevention of HNSCC.

PMID- 26207767
TI  - Prazosin Reduces Alcohol Intake in an Animal Model of Alcohol Relapse.
AB  - BACKGROUND: Many alcoholics and heavy drinkers undergo repeated cycles of alcohol
      abstinence followed by relapse to alcohol drinking; a pattern that contributes to
      escalated alcohol intake over time. In rodents, alcohol drinking that is
      interspersed with periods of alcohol deprivation (imposed abstinence) increases
      alcohol intake during reaccess to alcohol. This is termed the "alcohol
      deprivation effect" or "ADE" and is a model of alcohol relapse in humans. We have
      previously reported that prazosin reduces alcohol drinking during both brief and
      prolonged treatment in rats selectively bred for alcohol preference ("P" rats).
      This study explores whether prazosin prevents alcohol "relapse" in P rats, as
      reflected by a reduced or abolished ADE. METHODS: Adult male P rats were given 24
      hour access to food and water and scheduled access to alcohol (15 and 30% v/v
      solutions presented concurrently) for 2 h/d. After 5 weeks, rats underwent
      imposed alcohol deprivation for 2 weeks, followed by alcohol reaccess for 2
      weeks, and this pattern was repeated for a total of 3 cycles. Rats were injected
      with prazosin (0, 0.5, 1.0, or 2.0 mg/kg body weight, intraperitoneally) once a
      day for the first 5 days of each alcohol reaccess cycle. RESULTS: Alcohol intake
      increased on the first day of each alcohol reaccess cycle, demonstrating the
      formation of an ADE. The ADE was short-lived, lasting only 1 day, during each of
      the 3 cycles. Prazosin, in all doses tested, prevented the expression of an ADE
      in all 3 alcohol reaccess cycles. CONCLUSIONS: Prazosin decreases alcohol intake
      in P rats even in a situation that would be expected to increase alcohol
      drinking, namely following periods of alcohol deprivation. This suggests that
      prazosin may be effective in reducing alcohol relapse that often occurs during
      attempts to achieve permanent alcohol abstinence in treatment-seeking alcoholics
      and heavy drinkers.

PMID- 26207768
TI  - Anticraving Effect of Baclofen in Alcohol-Dependent Patients.
AB  - BACKGROUND: Baclofen is a GABA-B receptor agonist currently used in the treatment
      of spasticity. In recent years, baclofen has been used to reduce craving,
      voluntary alcohol intake and withdrawal syndrome of alcoholic patients. To date,
      there are no data available to estimate the relationship between baclofen
      exposure and the variation of craving. The first objective of this study was to
      investigate the variation of craving as a function of exposure, and the second
      was to explore the possible existence of baclofen responders and nonresponders.
      METHODS: Sixty-seven outpatients, 43 men/24 women (weight: 73 kg [42 to 128];
      age: 49 years old [29 to 68]) followed in the addictology unit, were studied
      during 3 months after treatment initiation. Baclofen was administered by oral
      route. Therapeutic drug monitoring enabled the measurement of plasma
      concentrations. Craving level was assessed by the Obsessive-Compulsive Drinking
      Scale (OCDS). A population pharmacokinetic (PK)-pharmacodynamic analysis of the
      OCDS variation following baclofen administration was performed. Demographic data,
      biological data, and tobacco consumption were tested for their influence on the
      parameters. RESULTS: Data were modeled with a 1-compartment model with first
      order absorption and elimination. PK analysis confirms the results of our
      previous study. An Emax model best-described the exposure-OCDS relationship. None
      of the covariates tested was able to improve the fit or decrease intersubject
      variability. However, 2 subpopulations were defined for the exposure
      corresponding to half the maximal effect (BE50). The proportion of patients being
      classified as responders was 38% (95% confidence interval [CI] 7 to 76), the
      maximal decrease in OCDS (Emax ) was 72% (95% CI 25 to 85), and the BE50 was 12.6
      (95% CI 0.02 to 74.3) or 4,390 (95% CI 20.4 to 31,800) h mg/l for responders and
      nonresponders, respectively. CONCLUSIONS: We defined the relationship between
      baclofen exposure and craving in patients with alcohol use disorder. Baclofen
      treatment decreased craving in all patients. However, we drew up the hypothesis
      of 2 subpopulations of patients differentiated by their speed of response. A wide
      interindividual variability in response was depicted, making it currently
      impossible to predict which group a patient will belong to.

PMID- 26207770
TI  - A dual-emissive ionic liquid based on an anionic platinum(ii) complex.
AB  - An ionic liquid fabricated from an anionic cyclometalated platinum(ii) complex
      and an imidazolium cation exhibits dual emission from the monomeric and
      aggregated forms of the platinum complex anions, leading to temperature-dependent
      color changes of luminescence. 

PMID- 26207771
TI  - Malignant Inflammatory Myofibroblastic Tumor of the Urinary Bladder in a 14-Year
      Old Boy.
AB  - Inflammatory myofibroblastic tumor (IMT) is an uncommon lesion with variable
      clinical behaviors from benign to mimicking malignant tumors. On rare occasions,
      IMT may exhibit malignant transformation, and the strategy of malignant IMT is
      remained undetermined. Herein, we report an extremely unusual case of IMT with
      malignant transformation of the urinary bladder in a 14-year-old boy
      characterized by local aggressive behavior and was successfully treated by
      combined surgery and perioperative chemotherapy. 

PMID- 26207769
TI  - Lipopolysaccharide Density and Structure Govern the Extent and Distance of
      Nanoparticle Interaction with Actual and Model Bacterial Outer Membranes.
AB  - Design of nanomedicines and nanoparticle-based antimicrobial and antifouling
      formulations and assessment of the potential implications of nanoparticle release
      into the environment requires understanding nanoparticle interaction with
      bacterial surfaces. Here we demonstrate the electrostatically driven association
      of functionalized nanoparticles with lipopolysaccharides of Gram-negative
      bacterial outer membranes and find that lipopolysaccharide structure influences
      the extent and location of binding relative to the outer leaflet-solution
      interface. By manipulating the lipopolysaccharide content in Shewanella
      oneidensis outer membranes, we observed the electrostatically driven interaction
      of cationic gold nanoparticles with the lipopolysaccharide-containing leaflet. We
      probed this interaction by quartz crystal microbalance with dissipation
      monitoring (QCM-D) and second harmonic generation (SHG) using solid-supported
      lipopolysaccharide-containing bilayers. The association of cationic nanoparticles
      increased with lipopolysaccharide content, while no association of anionic
      nanoparticles was observed. The harmonic-dependence of QCM-D measurements
      suggested that a population of the cationic nanoparticles was held at a distance
      from the outer leaflet-solution interface of bilayers containing smooth
      lipopolysaccharides (those bearing a long O-polysaccharide). Additionally, smooth
      lipopolysaccharides held the bulk of the associated cationic particles outside of
      the interfacial zone probed by SHG. Our results demonstrate that positively
      charged nanoparticles are more likely to interact with Gram-negative bacteria
      than are negatively charged particles, and this interaction occurs primarily
      through lipopolysaccharides. 

PMID- 26207772
TI  - The Clinical Significance of Initial Pulmonary Micronodules in Young Sarcoma
      Patients.
AB  - BACKGROUND: The clinical significance of subcentimeter nodules identified on
      staging chest computed tomography (CT) for sarcoma remains unknown. Our goal was
      to evaluate the effect of initial pulmonary nodule size and number on survival
      rates in young, newly diagnosed sarcoma patients. METHODS: Medical records were
      reviewed for all patients <=50 years of age with primary, high-grade bone or soft
      tissue sarcoma at our institution over a 10-year period. This population was
      divided into patients with no nodules (group 1); 1 nodule <5 mm (group 2);>1
      nodule <5 mm (group 3); and >=1 nodule >=5 mm (group 4). Kaplan-Meier analyses
      with log rank tests were performed to compare overall and disease-free survival
      between these 4 groups, as well as between patients with unilateral and bilateral
      nodules. RESULTS: There were 74 patients in group 1 (59.2%), 26 in group 2 (21%),
      11 in group 3 (9%), and 13 in group 4 (10%). Mean follow-up was 74 (range, 6 to
      191 mo) months. Survival was only slightly worse with larger nodules but
      significantly worse with multiple nodules. In addition, patients with bilateral
      nodules had a significantly worse prognosis than those with multiple unilateral
      nodules. CONCLUSIONS: These data suggest that in young patients with high-grade
      sarcoma, the number and distribution of subcentimeter pulmonary nodules are an
      important prognostic factor, whereas nodule size may be less relevant.

PMID- 26207773
TI  - High-dose Thiotepa as Consolidation Therapy With Autologous Hematopoietic Stem
      Cell Transplantation for High-risk Ewing Family Tumors: Single-institution
      Experience.
AB  - High-dose therapy (HDTx) with autologous stem cell rescue has been widely applied
      in very-poor-risk pediatric solid tumors. Promising data have become available
      with the use of high-dose busulfan, whereas high-dose (HD) thiotepa is less
      commonly used. We report retrospectively our single-institution experience from
      1986 to 2012 of single and tandem HDTx with special emphasis on HD-thiotepa as
      the backbone of HD regimen in Ewing family tumors, including all 24 patients in
      the Helsinki University Hospital referral area in population-based fashion (Ewing
      sarcoma 9, Askin tumor 9, peripheral neuroectodermal tumor 6). The 10-year
      overall survival for the entire cohort was 0.73+/-0.01. Thirteen out of the 24
      underwent HDTx (10 single, 3 tandem). The HDTx regimen consisted of HD-thiotepa
      (900 mg/m), VP16, and carboplatin. Additional HD-melphalan and total body
      irradiation were used in the tandem regimens. There was no toxic mortality. The 5
      year event-free survival was 0.73+/-0.16 for high-risk cases transplanted in 1CR.
      In the relapse group, 1 out of the 3 survived. Radiotherapy to axial sites was
      given safely in combination with HD-thiotepa in all 3 patients. Thiotepa-based
      HDTx approach resulted in an encouraging outcome without toxic mortality for high
      risk patients. HD-thiotepa merits further studies in larger controlled series. 

PMID- 26207774
TI  - Better Transition Readiness for Adolescents Begins With Effective Communication.

PMID- 26207775
TI  - Comparison of 3 Postthrombotic Syndrome Assessment Scales Demonstrates
      Significant Variability in Children and Adolescents With Deep Vein Thrombosis.
AB  - Postthrombotic syndrome (PTS) is an important outcome in children with deep vein
      thrombosis (DVT). There are several instruments to measure PTS, and no accepted
      "gold standard." The objective of this cross-sectional prospective study was to
      compare the prevalence of PTS in patients above 8 years old with a history of DVT
      using 3 scales: the Villalta scale, a pediatric modification of the Villalta
      scale, and the Manco-Johnson instrument. Forty-four subjects (22 females) were
      enrolled; mean age 16.6 years (SD 3.6 y). The majority had a lower extremity DVT.
      The average duration from DVT to PTS assessment was 2.6 years. The proportion of
      subjects with PTS using the adult Villalta scale was 11%, which was significantly
      less than the 66% of patients identified using both pediatric scales (P<0.0001).
      The majority of patients with PTS as determined by the pediatric scales had mild
      PTS. There was significant discordance between the prevalence of PTS using the
      Villalta scale compared with the 2 pediatric scales. This is especially relevant
      when considering which instrument to use in adolescent patients. This study
      demonstrates that PTS, as defined by these scales, is not a well-defined or
      standardized outcome, particularly when comparing adult and pediatric
      instruments. 

PMID- 26207776
TI  - An Infant With Congenital Leukemia Cutis and AML-M5 With MLL Gene Rearrangement.

PMID- 26207777
TI  - Motor Performance After Treatment for Pediatric Bone Tumors.
AB  - BACKGROUND: Reduced motor performance can negatively affect physical activity and
      social partake after childhood cancer. Especially in bone tumor patients, who are
      at risk of physical limitations due to surgical interventions, motor performance
      has not yet been sufficiently investigated. Therefore, this study aimed at
      assessing motor performance in pediatric bone tumor patients. PROCEDURE: Motor
      performance was measured within 2 years posttreatment using the MOON (test for
      MOtor performance in pediatric ONcology) test. This instrument enables
      quantitative data collection even in physically impaired patients for comparison
      with age-matched and sex-matched reference values. RESULTS: Twenty-one patients
      (13 male) ages 15.2+/-2.1 years (median: 15 y, 10 to 19 y) and 9.4+/-7.4 months
      posttreatment (median: 6 mo, 2 to 24 mo) were tested. Motor performance was
      slightly reduced in muscular endurance of the legs; significantly reduced in
      speed, flexibility, eye-hand coordination, and muscular explosive strength
      (P<0.001), whereas patients' hand grip strength and static balance were superior
      to the reference values. Follow-up duration, body mass index, and tumor
      localization apparently affected motor performance. CONCLUSIONS: These findings
      show serious reductions in motor performance within 2 years after bone tumor
      treatment and highlight the need for interventions to improve motor performance.
      The results should be used to advise and support patients to engage in suitable
      physical and sports activities.

PMID- 26207778
TI  - Oral Valganciclovir as Preemptive Therapy for Cytomegalovirus Reactivation in
      Pediatric Hematopoietic Stem Cell Transplant Patients.
AB  - Cytomegalovirus (CMV) infection is one of the most common complications after
      allogeneic hematopoietic stem cell transplantations (HSCT). Valganciclovir (VGC)
      has increasingly been used as prophylaxis against CMV infection after solid organ
      transplantation, but data on the efficacy and safety of VGC in pediatric HSCT
      patients are limited. We present our experience with VGC following ganciclovir
      (GCV) as preemptive therapy in pediatric HSCT patients. A total of 46 patients
      (38% patients) were found to be positive for CMV reactivation. Patients were
      treated with GCV (group I, n: 22) or GCV followed by VGC (GCV+VGC, group II, n:
      24). VGC was preferred in the treatment of outpatients, whereas inpatients were
      treated with GCV. There was no significant difference in CMV clearance (P=0.78),
      treatment duration (P=0.087), and second CMV infection (P=0.3) between the 2
      groups. The length of hospital stay was 21 days in GCV group, 14 days in VGC
      following GCV group (P=0.07). There were no treatment-related side effect in both
      groups. In conclusion, oral administration of VGC as preemptive therapy was found
      to be safe and effective. It is also a more suitable application for pediatric
      patients instead of an intravenous route. It could reduce the duration of
      inpatient stay and cost of hospitalization. 

PMID- 26207779
TI  - The Use of Ankaferd Blood Stopper in a Child With Glanzmann Thrombasthenia With
      Gingival Bleeding.

PMID- 26207780
TI  - Unexpected Anemia and Reticulocytopenia in an Adolescent With Sickle Cell Anemia
      Receiving Chronic Transfusion Therapy.
AB  - In a patient with sickle cell disease receiving chronic transfusion, exacerbation
      of anemia with reticulocytopenia must prompt consideration of a delayed hemolytic
      transfusion reaction with hyperhemolysis, as further transfusion may worsen this
      condition; definitive diagnosis is sometimes difficult. Anemia evolving during
      parvovirus B19-induced erythroid hypoplasia (transient aplastic crisis) should be
      attenuated in chronic transfusion patients due to superior survival of transfused
      over endogenous red blood cells. A 16-year-old with sickle cell disease receiving
      chronic transfusion of modified intensity (goal to maintain hemoglobin S<50%) who
      developed symptomatic anemia with reticulocytopenia was later shown to have had
      transient aplastic crisis. 

PMID- 26207781
TI  - Less sensitive oxygen-rich organic peroxides containing geminal hydroperoxy
      groups.
AB  - A series of oxygen-rich organic peroxide compounds each containing two
      bis(hydroperoxy)methylene groups is described. Energetic testing shows that these
      compounds are much less sensitive toward impact and friction than existing
      classes of organic peroxides. The compounds are highly energetic, which may lead
      to practical peroxide-based explosives. 

PMID- 26207782
TI  - Heparin Anticoagulation Monitoring in Patients Supported by Ventricular Assist
      Devices.

PMID- 26207784
TI  - Follow-up in Gynecological Malignancies: A State of Art.
AB  - OBJECTIVE: The main purpose of this article is to explore the current practice
      for follow-up of gynecological cancer, pointing out the different procedures, to
      determine the most clinically and cost-effective surveillance strategies after
      the primary treatment. MATERIALS AND METHODS: We analyzed the follow up
      strategies for ovarian, endometrial, and cervical cancer. All of the topics
      discussed below arose from the "ESGO State of Art Conference-Follow-up in
      gynaecological malignancies" in Turin, (September 11-13, 2014;
      http://torino2014.esgo.org/). RESULTS: Physical but these practices should be
      integrated with biomarkers or imaging strategies. Currently, most recommendations
      about follow-up are based on retrospective studies and expert opinion, and there
      is some disagreement on surveillance strategies due to lack of evidence-based
      knowledge. CONCLUSIONS: All surveillance procedures should be evidence-based with
      a clearly defined purpose: there is a need for prospective studies to compare the
      effectiveness of different follow-up regimens measuring overall survival,
      detection of recurrence, quality of life (QoL), and costs as outcomes.

PMID- 26207783
TI  - Derivation of Soil Ecological Criteria for Copper in Chinese Soils.
AB  - Considerable information on copper (Cu) ecotoxicity as affected by biological
      species and abiotic properties of soils has been collected from the last decade
      in the present study. The information on bioavailability/ecotoxicity, species
      sensitivity and differences in laboratory and field ecotoxicity of Cu in
      different soils was collated and integrated to derive soil ecological criteria
      for Cu in Chinese soils, which were expressed as predicted no effect
      concentrations (PNEC). First, all ecotoxicity data of Cu from bioassays based on
      Chinese soils were collected and screened with given criteria to compile a
      database. Second, the compiled data were corrected with leaching and aging
      factors to minimize the differences between laboratory and field conditions.
      Before Cu ecotoxicity data were entered into a species sensitivity distribution
      (SSD), they were normalized with Cu ecotoxicity predictive models to modify the
      effects of soil properties on Cu ecotoxicity. The PNEC value was set equal to the
      hazardous concentration for x% of the species (HCx), which could be calculated
      from the SSD curves, without an additional assessment factor. Finally, predictive
      models for HCx based on soil properties were developed. The soil properties had a
      significant effect on the magnitude of HCx, with HC5 varying from 13.1 mg/kg in
      acidic soils to 51.9 mg/kg in alkaline non-calcareous soils. The two-factor
      predictive models based on soil pH and cation exchange capacity could predict HCx
      with determination coefficients (R2) of 0.82-0.91. The three-factor predictive
      models--that took into account the effect of soil organic carbon--were more
      accurate than two-factor models, with R2 of 0.85-0.99. The predictive models
      obtained here could be used to calculate soil-specific criteria. All results
      obtained here could provide a scientific basis for revision of current Chinese
      soil environmental quality standards, and the approach adopted in this study
      could be used as a pragmatic framework for developing soil ecological criteria
      for other trace elements in soils.

PMID- 26207785
TI  - Assessing the Quality of Life in Patients With Endometrial Cancer Treated With
      Adjuvant Radiotherapy.
AB  - OBJECTIVE: The current study evaluates long-term quality of life (QOL) and sexual
      function of patients with endometrial cancer who received adjuvant pelvic
      external beam radiotherapy (EBRT) and/or vaginal brachytherapy (BRT). MATERIALS
      AND METHODS: One hundred forty-four endometrial cancer survivors who were treated
      between January 2000 and December 2009 in our department were included in this
      study. Median follow-up was 79 months (range, 31-138 months). Fifty-two patients
      were treated with 45 to 50.4 Gy EBRT, 76 were with BRT, and 16 were with both
      EBRT and BRT. Brachytherapy was in the form of vaginal cuff BRT with 5 * 550 cGy
      high dose rate BRT, prescribed to the first 4 cm and whole wall thickness of
      vagina. Quality of life was assessed using the European Organization for Research
      and Treatment of Cancer Quality of Life Questionnaire Core 30 and subscales from
      the supplemental 24-item Cervical Cancer Module. RESULTS: Vaginal BRT patients
      reported better physical functioning (P = 0.01), role functioning (P = 0.03), and
      sexual enjoyment (P = 0.01) compared to EBRT group. Symptom score (P = 0.01),
      lymphedema (P = 0.03), pain (P = 0.02), and diarrhea (P = 0.009) scores were also
      higher with EBRT. Vaginal BRT did not worsen symptom scores or sexual functions
      when added to EBRT. Obese patients experienced higher rates of lymphedema (P =
      0.008). Cognitive and role functioning scores were significantly higher in
      patients with normal body mass index. CONCLUSIONS: External beam radiotherapy
      negatively affects long-term QOL and sexual functions in endometrial cancer
      survivors. Vaginal BRT provides higher QOL. Patients with body mass index within
      normal limits have improved QOL.

PMID- 26207786
TI  - Enlarging the ring by incorporating a phosphonate coligand: from the cyclic
      hexanuclear to octanuclear dysprosium clusters.
AB  - Solvothermal reaction of a double pyrazinyl hydrazone ligand EDDC(2-) with
      Dy(OAc)3 results in a cyclic hexanuclear cluster
      [Dy6(EDDC)2(OAc)14(H2O)2].MeOH.2H2O (). The addition of 1-naphthylphosphonate to
      the reaction mixture expands the ring size with the formation of a cyclic
      octanuclear cluster [Dy8(EDDC)4(O3PC10H7)4(OAc)8(H2O)4].12H2O (). The latter
      shows slow magnetization relaxation below 12 K, characteristic of single molecule
      magnet behavior. 

PMID- 26207787
TI  - Metabolic tumor volume on interim PET is a better predictor of outcome in diffuse
      large B-cell lymphoma than semiquantitative methods.

PMID- 26207788
TI  - Multicellular cuddling in a stem cell niche.
AB  - Haematopoietic stem and progenitor cells (HSPCs) can self-renew and differentiate
      in any blood cell type throughout life and thereby sustain the entire blood
      system. To do so, HSPCs had been shown to seed, in a multi-step process,
      intermediate haematopoietic niches before colonizing the adult marrow. While HSPC
      birth had been thoroughly characterized in the past, both in mammals and in
      zebrafish, how perivascular niches could host HSPCs and sustain their expansion
      was poorly understood. In an article published in the last issue of Cell, Tamplin
      et al. (1) elegantly exploited the many advantages provided by the zebrafish
      embryo to describe how endothelium remodeling in the perivascular niche, referred
      to as "cuddling," favors HSPCs colonization and expansion.

PMID- 26207789
TI  - Protective Effects of Total Glucosides of Paeony on N-nitrosodiethylamine-induced
      Hepatocellular Carcinoma in Rats via Down-regulation of Regulatory B Cells.
AB  - Total glucoside of paeony (TGP), extracted from the root of Paeonia Lactiflora,
      has been known to show anti-inflammatory, anti-oxidative, hepato-protective and
      immuno-regulatory activities. The aim of this present study was to determine the
      anti-tumor effect of TGP against N-nitrosodiethylamine (DEN)-induced
      hepatocellular carcinoma (HCC) in rats, and to find the related mechanisms. Rat
      HCC model was established by intragastrically administrating with DEN (8 mg/kg).
      We found the number of tumor nodules and the index of liver and spleen were
      increased in the model group compared with the normal group, and was
      significantly decreased by TGP. Additionally, TGP obviously improved the hepatic
      pathological lesions induced by DEN, and decreased the elevated levels of serum
      alanine aminotransferase (ALT), glutamic oxalacetic transaminase (AST), alkaline
      phosphatase (ALP) and alpha fetoprotein (AFP) by DEN. Moreover, TGP decreased the
      level of B cell-activating factor (BAFF) and the proportion of IL-10-producing
      regulatory B cells (Bregs), and the decrease of BAFF by TGP is positively
      correlated to the decrease of IL-10-producing Bregs by TGP. These results suggest
      that TGP had a good therapeutic action on DEN-induced HCC rats, which might be
      due to its down-regulation of Bregs through reducing the level of BAFF. 

PMID- 26207790
TI  - Generation and Characterization of Human Single-Chain Antibodies Against
      Polycyclic Aromatic Hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widely distributed and relocated in
      the environment as a result of the incomplete combustion of organic matter. Many
      PAHs and their epoxides are highly toxic, mutagenic and/or carcinogenic to
      microorganisms as well as to higher systems including humans. BP is one of the
      most toxicologically active PAHs and is often used as a prototype for this entire
      class of contaminants. In order to select anti-BP antibodies, the conjugate of BP
      with BSA (BP-BSA) was used to screen naive combinatorial phage library of human
      scFvs. Seven unique scFvs against BP-BSA were selected after three rounds of
      selection. Analysis of the genes encoding the scFvs subdivided them to gene
      families and subfamilies. Homology with the closest germline ranged from 80.21%
      to 97.57% for heavy chains and 88.89% to 98.57% for the light chains. Four of the
      seven scFv amino acid residues sequences without stop codons in frame were
      selected for proteomic analysis with each other. Four scFvs encoded unique non
      related proteins with low-sequence identity among them. All CDRs and the
      boundaries in the CDR3 formation were carried out. Two of the scFvs (T68 and T72)
      with the highest binding capabilities to PAHs were expressed in E. coli and
      purified using a nickel resin. The KDs of T68 to BP-BSA, chrysene, pyrene, and
      benzo[a]anthracene were almost similar, approximately 10(-7 )M. The KDs of T72 to
      benzo[a]anthracene and chrysene were 9.42 * 10(-8 )M and 2.63 * 10(-7 )M,
      respectively. The computational models of T68 and T72 active centers were
      different. 

PMID- 26207791
TI  - Hannelore Wass: Professional Influences and Legacies.
AB  - This article offers a reflection on the professional influence of Dr. Hannelore
      Wass on the author's introduction to and work in the field of death, dying, and
      bereavement. At the same time, it also offers comments on her broader influence
      on and legacies left to others who work in this field. 

PMID- 26207792
TI  - A Systematic Comparison of Traditional and Multigene Panel Testing for Hereditary
      Breast and Ovarian Cancer Genes in More Than 1000 Patients.
AB  - Gene panels for hereditary breast and ovarian cancer risk assessment are gaining
      acceptance, even though the clinical utility of these panels is not yet fully
      defined. Technical questions remain, however, about the performance and clinical
      interpretation of gene panels in comparison with traditional tests. We tested
      1105 individuals using a 29-gene next-generation sequencing panel and observed
      100% analytical concordance with traditional and reference data on >750
      comparable variants. These 750 variants included technically challenging classes
      of sequence and copy number variation that together represent a significant
      fraction (13.4%) of the pathogenic variants observed. For BRCA1 and BRCA2, we
      also compared variant interpretations in traditional reports to those produced
      using only non-proprietary resources and following criteria based on recent
      (2015) guidelines. We observed 99.8% net report concordance, albeit with a
      slightly higher variant of uncertain significance rate. In 4.5% of BRCA-negative
      cases, we uncovered pathogenic variants in other genes, which appear clinically
      relevant. Previously unseen variants requiring interpretation accumulated
      rapidly, even after 1000 individuals had been tested. We conclude that next
      generation sequencing panel testing can provide results highly comparable to
      traditional testing and can uncover potentially actionable findings that may be
      otherwise missed. Challenges remain for the broad adoption of panel tests, some
      of which will be addressed by the accumulation of large public databases of
      annotated clinical variants. 

PMID- 26207793
TI  - ?

PMID- 26207794
TI  - ?

PMID- 26207795
TI  - ?

PMID- 26207796
TI  - ?

PMID- 26207797
TI  - The antioxidant effect of ubiquinone and combined therapy on mitochondrial
      function in blood cells in non-proliferative diabetic retinopathy: A randomized,
      double-blind, phase IIa, placebo-controlled study.
AB  - OBJECTIVES: To evaluate the effect of ubiquinone and combined antioxidant therapy
      on mitochondrial function in non-proliferative diabetic retinopathy (NPDR) in a
      randomized, double-blind, phase IIa, placebo-controlled, clinical trial. Three
      groups of 20 patients were formed: Group 1, ubiquinone; Group 2, combined
      therapy; and Group 3, placebo (one daily dose for 6 months). METHODS: Fluidity of
      the submitochondrial membrane in platelets was determined by examining intensity
      of fluorescence between the monomer (Im) and excimer (Ie). Hydrolytic activity of
      the mitochondrial F0F1-ATPase was evaluated with the spectrophotometric method.
      RESULTS: Normal, baseline submitochondrial membrane fluidity, 0.24 +/- 0.01
      Ie/Im, was significantly diminished in the three study groups vs. normal values
      (P < 0.0001); placebo, 0.14 +/- 0.01 Ie/Im; ubiquinone, 0.14 +/- 0.01 Ie/Im; and
      combined therapy, 0.13 +/- 0.00 Ie/Im. Afterward, it increased significantly (P <
      0.0001), the ubiquinone group 0.22 +/- 0.01 Ie/Im, combined therapy group, 0.19
      +/- 0.01 Ie/Im; with no changes the placebo group. Baseline hydrolytic activity
      of the F0F1-ATPase enzyme increased in the three study groups vs. normal values
      (184.50 +/- 7.84 nmol PO4), placebo, 304.12 +/- 22.83 nmol PO4 (P < 0.002);
      ubiquinone, 312.41 +/- 25.63 nmol PO4 (P < 0.009); and combined therapy, 371.28
      +/- 33.50 nmol PO4 (P < 0.002). Afterward, a significant decrease the enzymatic
      activity: ubiquinone, 213.25 +/- 14.19 nmol PO4 (P < 0.001); and combined
      therapy, 225.55 +/- 14.48 nmol PO4 (P < 0.0001). DISCUSSION: Mitochondrial
      dysfunction significantly improved in groups of NPDR patients treated with
      antioxidants.

PMID- 26207798
TI  - Predisposition to depression and implicit emotion processing.
AB  - Depression, one of the most widespread mental disorders, is associated with
      considerable alterations in emotional functioning. It is unclear whether these
      alterations are associated with clinical depression or exist already at
      preclinical stages. Here, in clinically healthy individuals, a combination of
      neuroticism and introversion was used as a predisposition to depression (PD)
      scale. Participants were presented with pictures of emotional facial expressions
      and performed the gender discrimination task, while their electroencephalogram
      (EEG) was recorded. The affective processing bias (i.e., longer reaction time and
      higher error rate for angry faces) was found in low, but not in high PD scorers.
      High PD scorers also showed reduced theta synchronization and enhanced alpha
      desynchronization in the test interval and higher delta and theta power in the
      interstimuli interval. The latter effect implies that activity of emotional
      circuits, which is mirrored in low-frequency oscillations, is tonically increased
      in predisposed-to-depression individuals, thus precluding an adequate response to
      external emotional cues. This results in unspecific general activation reflected
      in enhanced alpha desynchronization and in disrupted ability to differentiate
      incoming emotional information. 

PMID- 26207800
TI  - Structural and mechanistic analysis of engineered trichodiene synthase enzymes
      from Trichoderma harzianum: towards higher catalytic activities empowering
      sustainable agriculture.
AB  - Trichoderma spp. are well-known bioagents for the plant growth promotion and
      pathogen suppression. The beneficial activities of the fungus Trichoderma spp.
      are attributed to their ability to produce and secrete certain secondary
      metabolites such as trichodermin that belongs to trichothecene family of
      molecules. The initial steps of trichodermin biosynthetic pathway in Trichoderma
      are similar to the trichothecenes from Fusarium sporotrichioides. Trichodiene
      synthase (TS) encoded by tri5 gene in Trichoderma catalyses the conversion of
      farnesyl pyrophosphate to trichodiene as reported earlier. In this study, we have
      carried out a comprehensive comparative sequence and structural analysis of the
      TS, which revealed the conserved residues involved in catalytic activity of the
      protein. In silico, modelled tertiary structure of TS protein showed stable
      structural behaviour during simulations. Two single-substitution mutants, i.e.
      D109E, D248Y and one double-substitution mutant (D109E and D248Y) of TS with
      potentially higher activities are screened out. The mutant proteins showed more
      stability than the wild type, an increased number of electrostatic interactions
      and better binding energies with the ligand, which further elucidates the amino
      acid residues involved in the reaction mechanism. These results will lead to
      devise strategies for higher TS activity to ultimately enhance the trichodermin
      production by Trichoderma spp. for its better exploitation in the sustainable
      agricultural practices. 

PMID- 26207799
TI  - Differential effects of Sp cellular transcription factors on viral promoter
      activation by varicella-zoster virus (VZV) IE62 protein.
AB  - The immediate early (IE) 62 protein is the major varicella-zoster virus (VZV)
      regulatory factor. Analysis of the VZV genome revealed 40 predicted GC-rich boxes
      within 36 promoters. We examined effects of ectopic expression of Sp1-Sp4 on IE62
      mediated transactivation of three viral promoters. Ectopic expression of Sp3 and
      Sp4 enhanced IE62 activation of ORF3 and gI promoters while Sp3 reduced IE62
      activation of ORF28/29 promoter and VZV DNA replication. Sp2 reduced IE62
      transactivation of gI while Sp1 had no significant influence on IE62 activation
      with any of these viral promoters. Electrophoretic mobility shift assays (EMSA)
      confirmed binding of Sp1 and Sp3 but not Sp2 and Sp4 to the gI promoter. Sp1-4
      bound to IE62 and amino acids 238-258 of IE62 were important for the interaction
      with Sp3 and Sp4 as well as Sp1. This work shows that Sp family members have
      differential effects on IE62-mediated transactivation in a promoter-dependent
      manner. 

PMID- 26207801
TI  - Factors influencing the person-carer relationship in people with anxiety and
      dementia.
AB  - OBJECTIVE: The relationship between people with dementia and their carers is
      complex and has a significant impact on the dementia experience. The aim of this
      current study was to determine (1) which factors are associated with the quality
      of the patient-carer relationship and (2) whether these differ between the two
      perspectives. METHOD: Participants (people with dementia and their carers) were
      taken from a randomised controlled trial of cognitive behaviour therapy for
      anxiety in dementia. The quality of the relationship from both perspectives,
      anxiety and depression in both parties; and the quality of life, neuropsychiatric
      symptoms and cognitive functioning in people with dementia was examined at three
      time points (baseline, 15 weeks and 6 months). RESULTS: There were 127
      observations from 50 dyads (100 individuals) across the three time points.
      Factors significantly related to quality of relationship from the person with
      dementia's perspective were their own aggression, agitation, irritability,
      depression, anxiety and quality of life. Factors significantly associated with
      quality of relationship from the carer's perspective were their own anxiety and
      depression, and the depression, irritability, behavioural disturbances and
      quality of life of the person with dementia. People with dementia generally rated
      the quality of relationship higher, irrespective of level of dementia, depression
      or anxiety. CONCLUSION: This study is novel in that it provides a valuable
      insight into the impact of mental health on relationship quality for both members
      of the dyad. The findings emphasise the importance of providing interventions
      which target mood for both parties, and behavioural problems for people with
      dementia.

PMID- 26207802
TI  - Rotating Anisotropic Crystalline Silicon Nanoclusters in Graphene.
AB  - The atomic structure and dynamics of silicon nanoclusters covalently bonded to
      graphene are studied using aberration-corrected transmission electron microscopy.
      We show that as the cluster size increases to 4-10 atoms, ordered crystalline
      cubic phases start to emerge. Anisotropic crystals are formed due to higher
      stability of the Si-C bond under electron beam irradiation compared to the Si-Si
      bond. Dynamics of the anisotropic crystalline Si nanoclusters reveal that they
      can rotate perpendicular to the graphene plane, with oscillations between the two
      geometric configurations driven by local volume constraints. These results
      provide important insights into the crystalline phases of clusters of inorganic
      dopants in graphene at the intermediate size range between isolated single atoms
      and larger bulk 2D forms. 

PMID- 26207803
TI  - A patient preference conservative management of recurrent TVT vaginal erosion.

PMID- 26207804
TI  - Precision Medicine: At What Price?

PMID- 26207805
TI  - Protecting non-combatant civilians during war.

PMID- 26207806
TI  - Is Acupuncture Effective for Hypertension? A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To determine the efficacy of acupuncture for hypertension. METHOD:
      Seven electronic databases were searched on April 13, 2014 to include eligible
      randomized controlled trials (RCTs). Data were extracted and risk of bias was
      assessed. Subgroup analyses and meta- analysis were performed. RESULTS: 23 RCTs
      involving 1788 patients were included. Most trials had an unclear risk of bias
      regarding allocation concealment, blinding, incomplete outcome data and selective
      reporting. Compared with sham acupuncture plus medication, a meta-analysis of 2
      trials revealed that acupuncture as an adjunct to medication was more effective
      on systolic (SBP) and diastolic (DBP) blood pressure change magnitude (n=170,
      SBP: mean difference (MD)= -7.47,95% confidence intervals (CI):-10.43 to -4.51,I2
      =0%; DBP: -4.22,-6.26 to -2.18, 0%).A subgroup analysis of 4 trials also showed
      acupuncture combined with medication was superior to medication on efficacy rate
      (n=230, odds ratio (OR)=4.19, 95%CI: 1.65 to 10.67, I2 =0%). By contrast,
      compared with medication, acupuncture alone showed no significant effect on SBP
      /DBP after intervention and efficacy rate in the subgroup analysis. (7 trials
      with 510 patients, SBP: MD=-0.56, 95%CI:-3.02 to 1.89,I2 =60%; DBP: -1.01,-2.26
      to 0.24, 23%; efficacy rate: 10 trials with 963 patients, OR=1.14, 95% CI: 0.70
      to 1.85, I2 =54%).Adverse events were inadequately reported in most RCTs.
      CONCLUSION: Our review provided evidence of acupuncture as an adjunctive therapy
      to medication for treating hypertension, while the evidence for acupuncture alone
      lowing BP is insufficient. The safety of acupuncture is uncertain due to the
      inadequate reporting of it. However, the current evidence might not be
      sufficiently robust against methodological flaws and significant heterogeneity of
      the included RCTs. Larger high-quality trials are required.

PMID- 26207807
TI  - Cation Clock Reactions for the Determination of Relative Reaction Kinetics in
      Glycosylation Reactions: Applications to Gluco- and Mannopyranosyl Sulfoxide and
      Trichloroacetimidate Type Donors.
AB  - The development of a cation clock method based on the intramolecular Sakurai
      reaction for probing the concentration dependence of the nucleophile in
      glycosylation reactions is described. The method is developed for the sulfoxide
      and trichloroacetimidate glycosylation protocols. The method reveals that O
      glycosylation reactions have stronger concentration dependencies than C
      glycosylation reactions consistent with a more associative, S(N)2-like character.
      For the 4,6-O-benzylidene-directed mannosylation reaction a significant
      difference in concentration dependence is found for the formation of the beta-
      and alpha-anomers, suggesting a difference in mechanism and a rationale for the
      optimization of selectivity regardless of the type of donor employed. In the
      mannose series the cyclization reaction employed as clock results in the
      formation of cis and trans-fused oxabicyclo[4,4,0]decanes as products with the
      latter being strongly indicative of the involvement of a conformationally mobile
      transient glycosyl oxocarbenium ion. With identical protecting group arrays
      cyclization in the glucopyranose series is more rapid than in the mannopyranose
      manifold. The potential application of related clock reactions in other carbenium
      ion-based branches of organic synthesis is considered.

PMID- 26207808
TI  - Adapted Prescription Dose for Monte Carlo Algorithm in Lung SBRT: Clinical
      Outcome on 205 Patients.
AB  - PURPOSE: SBRT is the standard of care for inoperable patients with early-stage
      lung cancer without lymph node involvement. Excellent local control rates have
      been reported in a large number of series. However, prescription doses and
      calculation algorithms vary to a great extent between studies, even if most teams
      prescribe to the D95 of the PTV. Type A algorithms are known to produce
      dosimetric discrepancies in heterogeneous tissues such as lungs. This study was
      performed to present a Monte Carlo (MC) prescription dose for NSCLC adapted to
      lesion size and location and compare the clinical outcomes of two cohorts of
      patients treated with a standard prescription dose calculated by a type A
      algorithm or the proposed MC protocol. PATIENTS AND METHODS: Patients were
      treated from January 2011 to April 2013 with a type B algorithm (MC) prescription
      with 54 Gy in three fractions for peripheral lesions with a diameter under 30 mm,
      60 Gy in 3 fractions for lesions with a diameter over 30 mm, and 55 Gy in five
      fractions for central lesions. Clinical outcome was compared to a series of 121
      patients treated with a type A algorithm (TA) with three fractions of 20 Gy for
      peripheral lesions and 60 Gy in five fractions for central lesions prescribed to
      the PTV D95 until January 2011. All treatment plans were recalculated with both
      algorithms for this study. Spearman's rank correlation coefficient was calculated
      for GTV and PTV. Local control, overall survival and toxicity were compared
      between the two groups. RESULTS: 205 patients with 214 lesions were included in
      the study. Among these, 93 lesions were treated with MC and 121 were treated with
      TA. Overall survival rates were 86% and 94% at one and two years, respectively.
      Local control rates were 79% and 93% at one and two years respectively. There was
      no significant difference between the two groups for overall survival (p = 0.785)
      or local control (p = 0.934). Fifty-six patients (27%) developed grade I lung
      fibrosis without clinical consequences. GTV size was a prognostic factor for
      overall survival (HR = 1.026, IC95% [1.01-1.041], p<0.001) and total dose was a
      prognostic factor for local control (HR = 0.924, IC95% [0.870-0.982], p = 0.011).
      D50 of the GTV calculated with MC correlated poorly with the D95 of the PTV
      calculated with TA (r = 0.116) for lesions with a diameter of 20 mm or less. For
      lesions larger than 20 mm, spearman correlation was higher (r = 0.618), but still
      insufficient. CONCLUSION: No difference in local control or overall survival was
      found between patients treated with a type A or a type B algorithm in our cohort.
      A size and location adapted GTV-based prescription method could be used with a
      type B algorithm. External validation of these results is warranted.

PMID- 26207809
TI  - In Silico Analysis of Tumor Necrosis Factor alpha-Induced Protein 8-Like-1
      (TIPE1) Protein.
AB  - Tumor necrosis factor alpha-induced protein 8 (TNFAIP8)-like protein 1 (TIPE1)
      was a member of TNFAIP8 family. Previous studies have shown that TIPE1 could
      induce apoptosis in hepatocellular carcinoma. In this study, we attempted to
      predict its potential structure. Bioinformatic analysis of TIPE1 was performed to
      predict its potential structure using the bioinfomatic web services or softwares.
      The results showed that the amino acid sequences of TIPE1 were well conserved in
      mammals. No signal peptide and no transmembrane domain existed in human TIPE1.
      The aliphatic index of TIPE1 was 100.75 and the theoretical pI was 9.57. TIPE1
      was a kind of stable protein and its grand average of hydropathicity was -0.108.
      Various post-translational modifications were also speculated to exist in TIPE1.
      In addition, the results of Swiss-Model Server and Swiss-Pdb Viewer program
      revealed that the predicted three-dimensional structure of TIPE1 protein was
      stable and it may accord with the rule of stereochemistry. TIPE1 was predicted to
      interact with FBXW5, caspase8 and so on. In conclusion, TIPE1 may be a stable
      protein with no signal peptide and no transmembrane domain. The bioinformatic
      analysis of TIPE1 will provide the basis for the further study on the function of
      TIPE1. 

PMID- 26207810
TI  - The FKBP52 Cochaperone Acts in Synergy with beta-Catenin to Potentiate Androgen
      Receptor Signaling.
AB  - FKBP52 and beta-catenin have emerged in recent years as attractive targets for
      prostate cancer treatment. beta-catenin interacts directly with the androgen
      receptor (AR) and has been characterized as a co-activator of AR-mediated
      transcription. FKBP52 is a positive regulator of AR in cellular and whole animal
      models and is required for the development of androgen-dependent tissues. We
      previously characterized an AR inhibitor termed MJC13 that putatively targets the
      AR BF3 surface to specifically inhibit FKBP52-regulated AR signaling. Predictive
      modeling suggests that beta-catenin interacts with the AR hormone binding domain
      on a surface that overlaps with BF3. Here we demonstrate that FKBP52 and beta
      catenin interact directly in vitro and act in concert to promote a synergistic up
      regulation of both hormone-independent and -dependent AR signaling. Our data
      demonstrate that FKBP52 promotes beta-catenin interaction with AR and is required
      for beta-catenin co-activation of AR activity in prostate cancer cells. MJC13
      effectively blocks beta-catenin interaction with the AR LBD and the synergistic
      up-regulation of AR by FKBP52 and beta-catenin. Our data suggest that co
      regulation of AR by FKBP52 and beta-catenin does not require FKBP52 PPIase
      catalytic activity, nor FKBP52 binding to Hsp90. However, the FKBP52 proline-rich
      loop that overhangs the PPIase pocket is critical for synergy. 

PMID- 26207811
TI  - Gene Expression in Experimental Aortic Coarctation and Repair: Candidate Genes
      for Therapeutic Intervention?
AB  - Coarctation of the aorta (CoA) is a constriction of the proximal descending
      thoracic aorta and is one of the most common congenital cardiovascular defects.
      Treatments for CoA improve life expectancy, but morbidity persists, particularly
      due to the development of chronic hypertension (HTN). Identifying the mechanisms
      of morbidity is difficult in humans due to confounding variables such as age at
      repair, follow-up duration, coarctation severity and concurrent anomalies. We
      previously developed an experimental model that replicates aortic pathology in
      humans with CoA without these confounding variables, and mimics correction at
      various times using dissolvable suture. Here we present the most comprehensive
      description of differentially expressed genes (DEGs) to date from the pathology
      of CoA, which were obtained using this model. Aortic samples (n=4/group) from the
      ascending aorta that experiences elevated blood pressure (BP) from induction of
      CoA, and restoration of normal BP after its correction, were analyzed by gene
      expression microarray, and enriched genes were converted to human orthologues. 51
      DEGs with >6 fold-change (FC) were used to determine enriched Gene Ontology
      terms, altered pathways, and association with National Library of Medicine
      Medical Subject Headers (MeSH) IDs for HTN, cardiovascular disease (CVD) and CoA.
      The results generated 18 pathways, 4 of which (cell cycle, immune system,
      hemostasis and metabolism) were shared with MeSH ID's for HTN and CVD, and
      individual genes were associated with the CoA MeSH ID. A thorough literature
      search further uncovered association with contractile, cytoskeletal and
      regulatory proteins related to excitation-contraction coupling and metabolism
      that may explain the structural and functional changes observed in our
      experimental model, and ultimately help to unravel the mechanisms responsible for
      persistent morbidity after treatment for CoA. 

PMID- 26207813
TI  - Comparative Transcriptomes Analysis of Red- and White-Fleshed Apples in an F1
      Population of Malus sieversii f. niedzwetzkyana Crossed with M. domestica 'Fuji'.
AB  - Transcriptome profiles of the red- and white-fleshed apples in an F1 segregating
      population of Malus sieversii f.Niedzwetzkyana and M.domestica 'Fuji' were
      generated using the next-generation high-throughput RNA sequencing (RNA-Seq)
      technology and compared. A total of 114 differentially expressed genes (DEGs)
      were obtained, of which 88 were up-regulated and 26 were down-regulated in red
      fleshed apples. The 88 up-regulated genes were enriched with those related to
      flavonoid biosynthetic process and stress responses. Further analysis identified
      22 genes associated with flavonoid biosynthetic process and 68 genes that may be
      related to stress responses. Furthermore, the expression of 20 up-regulated
      candidate genes (10 related to flavonoid biosynthesis, two encoding MYB
      transcription factors and eight related to stress responses) and 10 down
      regulated genes were validated by quantitative real-time PCR. After exploring the
      possible regulatory network, we speculated that flavonoid metabolism might be
      involved in stress responses in red-fleshed apple. Our findings provide a
      theoretical basis for further enriching gene resources associated with flavonoid
      synthesis and stress responses of fruit trees and for breeding elite apples with
      high flavonoid content and/or increased stress tolerances. 

PMID- 26207814
TI  - Association of Altered Serum MicroRNAs with Perihematomal Edema after Acute
      Intracerebral Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Perihematomal edema (PHE) contributes to secondary brain
      damage and aggravates patient outcomes after intracerebral hemorrhage (ICH).
      MicroRNAs (miRNAs) are stable in circulation, and their unique expression
      profiles have fundamental roles in modulating vascular disease. The objective of
      this study was to test the hypothesis that altered miRNA levels are associated
      with PHE in ICH patients. METHODS: Hematoma and PHE volumes of ICH patients were
      measured on admission and in follow-up computed tomography scans. Whole-genome
      miRNA profiles of ICH patients and healthy controls were determined using the
      Exiqon miRCURY LNA Array, and validated by quantitative reverse transcription
      polymerase chain reaction (qRT-PCR). Bioinformatics analysis investigated
      dysregulated miRNA target genes and the signaling pathways involved. RESULTS: We
      identified 55 miRNAs that were differentially expressed in ICH patients compared
      with normal controls, of which 54 were down-regulated and one was up-regulated.
      qRT-PCR confirmation showed decreases in miR-126 (0.63-fold), miR-146a (0.64
      fold), miR-let-7a (0.50-fold), and miR-26a (0.54-fold) in ICH patients relative
      to controls. Serum miR-126, but not miR-146a, miR-let-7a or miR-26a, levels were
      significantly correlated with relative PHE volume on days 3-4 (r = -0.714;
      P<0.001) in patients with ICH. CONCLUSIONS: ICH patients appear to have a
      specific miRNA expression profile. Low expression of miR-126 was positively
      correlated with the extent of PHE, suggesting it may have a pathogenic role in
      the development of PHE after ICH.

PMID- 26207815
TI  - A Novel Homozygous TBC1D24 Mutation Causing Multifocal Myoclonus With Cerebellar
      Involvement.

PMID- 26207812
TI  - Elevated Genetic Diversity in the Emerging Blueberry Pathogen Exobasidium
      maculosum.
AB  - Emerging diseases caused by fungi are increasing at an alarming rate. Exobasidium
      leaf and fruit spot of blueberry, caused by the fungus Exobasidium maculosum, is
      an emerging disease that has rapidly increased in prevalence throughout the
      southeastern USA, severely reducing fruit quality in some plantings. The
      objectives of this study were to determine the genetic diversity of E. maculosum
      in the southeastern USA to elucidate the basis of disease emergence and to
      investigate if populations of E. maculosum are structured by geography, host
      species, or tissue type. We sequenced three conserved loci from 82 isolates
      collected from leaves and fruit of rabbiteye blueberry (Vaccinium virgatum),
      highbush blueberry (V. corymbosum), and southern highbush blueberry (V.
      corymbosum hybrids) from commercial fields in Georgia and North Carolina, USA,
      and 6 isolates from lowbush blueberry (V. angustifolium) from Maine, USA, and
      Nova Scotia, Canada. Populations of E. maculosum from the southeastern USA and
      from lowbush blueberry in Maine and Nova Scotia are distinct, but do not
      represent unique species. No difference in genetic structure was detected between
      different host tissues or among different host species within the southeastern
      USA; however, differentiation was detected between populations in Georgia and
      North Carolina. Overall, E. maculosum showed extreme genetic diversity within the
      conserved loci with 286 segregating sites among the 1,775 sequenced nucleotides
      and each isolate representing a unique multilocus haplotype. However, 94% of the
      nucleotide substitutions were silent, so despite the high number of mutations,
      selective constraints have limited changes to the amino acid sequences of the
      housekeeping genes. Overall, these results suggest that the emergence of
      Exobasidium leaf and fruit spot is not due to a recent introduction or host
      shift, or the recent evolution of aggressive genotypes of E. maculosum, but more
      likely as a result of an increasing host population or an environmental change. 

PMID- 26207816
TI  - Soil charcoal as long-term pyrogenic carbon storage in Amazonian seasonal
      forests.
AB  - Forest fires (paleo + modern) have caused charcoal particles to accumulate in the
      soil vertical profile in Amazonia. This forest compartment is a long-term carbon
      reservoir with an important role in global carbon balance. Estimates of stocks
      remain uncertain in forests that have not been altered by deforestation but that
      have been impacted by understory fires and selective logging. We estimated the
      stock of pyrogenic carbon derived from charcoal accumulated in the soil profile
      of seasonal forest fragments impacted by fire and selective logging in the
      northern portion of Brazilian Amazonia. Sixty-nine soil cores to 1-m depth were
      collected in 12 forest fragments of different sizes. Charcoal stocks averaged
      3.45 +/- 2.17 Mg ha(-1) (2.24 +/- 1.41 Mg C ha(-1) ). Pyrogenic carbon was not
      directly related to the size of the forest fragments. This carbon is equivalent
      to 1.40% (0.25% to 4.04%) of the carbon stocked in aboveground live tree biomass
      in these fragments. The vertical distribution of pyrogenic carbon indicates an
      exponential model, where the 0-30 cm depth range has 60% of the total stored. The
      total area of Brazil's Amazonian seasonal forests and ecotones not altered by
      deforestation implies 65-286 Tg of pyrogenic carbon accumulated along the soil
      vertical profile. This is 1.2-2.3 times the total amount of residual pyrogenic
      carbon formed by biomass burning worldwide in 1 year. Our analysis suggests that
      the accumulated charcoal in the soil vertical profile in Amazonian forests is a
      substantial pyrogenic carbon pool that needs to be considered in global carbon
      models.

PMID- 26207817
TI  - Petasites japonicus Stimulates the Proliferation of Mouse Spermatogonial Stem
      Cells.
AB  - Oriental natural plants have been used as medical herbs for the treatment of
      various diseases for over 2,000 years. In this study, we evaluated the effect of
      several natural plants on the preservation of male fertility by assessing the
      ability of plant extracts to stimulate spermatogonial stem cell (SSC)
      proliferation by using a serum-free culture method. In vitro assays showed that
      Petasites japonicus extracts, especially the butanol fraction, have a significant
      effect on germ cells proliferation including SSCs. The activity of SSCs cultured
      in the presence of the Petasites japonicus butanol fraction was confirmed by
      normal colony formation and spermatogenesis following germ cell transplantation
      of the treated SSCs. Our findings could lead to the discovery of novel factors
      that activate SSCs and could be useful for the development of technologies for
      the prevention of male infertility. 

PMID- 26207819
TI  - Hofmeister Effects in Monoclonal Antibody Solution Interactions.
AB  - By using static and dynamic light scattering (SLS and DLS), we investigate the
      effect of ion specificity and solution conditions on the solution behavior of
      monoclonal antibodies (mAbs). The extracted second virial coefficient, a global
      measure of the strength of protein-protein interactions, shows a complicated,
      nonmonotonic behavior. It can be connected on one side with the Hofmeister
      effect, and on the other with the interplay of screening and charge fluctuations
      in inhomogeneous, patchy charge distribution of these particular proteins.
      Although direct quantification in terms of the underlying long and short-range
      potentials is out of reach, the observed effects do point toward important
      features of mAbs solution aggregation processes that are governed by the identity
      of the solution ions as well as by details of the charge distribution of
      interacting proteins. 

PMID- 26207818
TI  - Neuromedin B Restores Erectile Function by Protecting the Cavernous Body and the
      Nitrergic Nerves from Injury in a Diabetic Rat Model.
AB  - Erectile dysfunction (ED) is a major health problem worldwide and affects
      approximately 75% of diabetic patients, likely due to severely damaged cavernous
      body. While screening for cytokines produced by adipose tissue-derived stem
      cells, we detected neuromedin B (NMB). To explore a potential treatment option
      for ED, we examined whether NMB was capable of restoring erectile function. We
      also examined the potential mechanism by which NMB could restore erectile
      function. Male Wistar rats were injected with streptozotocin (STZ) to induce
      diabetes. An adenovirus expressing NMB (AdNMB) was injected into the penis 6
      weeks after STZ administration. Four weeks after the injection of AdNMB, erectile
      function, penile histology, and protein expression were analyzed. As assessed by
      the measurement of intracavernous pressure, AdNMB injection significantly
      restored erectile function compared with the injection of an adenovirus
      expressing green fluorescent protein. This restoration was associated with
      conservation of the cavernous body structure and neural nitric oxide synthase
      (nNOS)-expressing nerves, together with recovery of alpha-smooth muscle actin,
      vascular endothelial-cadherin, and nNOS expression. Furthermore, NMB
      significantly stimulated the survival of SH-SY5Y cells derived from human
      neuroblastoma tissue with characteristics similar to neurons. Collectively, these
      results suggested that NMB restored erectile function via protection of the
      cavernous body from injury and stimulation of the survival of the associated
      nerves. NMB may be useful to treat ED patients with a severely damaged cavernous
      body. 

PMID- 26207820
TI  - Immunization with a Recombinant, Pseudomonas fluorescens-Expressed, Mutant Form
      of Bacillus anthracis-Derived Protective Antigen Protects Rabbits from Anthrax
      Infection.
AB  - Protective antigen (PA), one of the components of the anthrax toxin, is the major
      component of human anthrax vaccine (Biothrax). Human anthrax vaccines approved in
      the United States and Europe consist of an alum-adsorbed or precipitated
      (respectively) supernatant material derived from cultures of toxigenic, non
      encapsulated strains of Bacillus anthracis. Approved vaccination schedules in
      humans with either of these vaccines requires several booster shots and
      occasionally causes adverse injection site reactions. Mutant derivatives of the
      protective antigen that will not form the anthrax toxins have been described. We
      have cloned and expressed both mutant (PA SNKE167-DeltaFF-315-E308D) and native
      PA molecules recombinantly and purified them. In this study, both the mutant and
      native PA molecules, formulated with alum (Alhydrogel), elicited high titers of
      anthrax toxin neutralizing anti-PA antibodies in New Zealand White rabbits. Both
      mutant and native PA vaccine preparations protected rabbits from lethal,
      aerosolized, B. anthracis spore challenge subsequent to two immunizations at
      doses of less than 1 MUg. 

PMID- 26207821
TI  - Investigation of temperature and barometric pressure variation effects on radon
      concentration in the Sopronbanfalva Geodynamic Observatory, Hungary.
AB  - Radon concentration variation has been monitored since 2009 in the artificial
      gallery of the Sopronbanfalva Geodynamic Observatory, Hungary. In the
      observatory, the radon concentration is extremely high, 100-600 kBq m(-3) in
      summer and some kBq m(-3) in winter. The relationships between radon
      concentration, temperature and barometric pressure were separately investigated
      in the summer and winter months by Fast Fourier Transform, Principal Component
      Analysis, Multivariable Regression and Partial Least Square analyses in different
      frequency bands. It was revealed that the long-period radon concentration
      variation is mainly governed by the temperature (20 kBq m(-1)  degrees C(-1))
      both in summer and winter. The regression coefficients between long-period radon
      concentration and barometric pressure are -1.5 kBq m(-3) hPa(-1) in the summer
      and 5 kBq m(-3) hPa(-1) in the winter months. In the 0.072-0.48 cpd (cycles per
      day) frequency band the effect of the temperature is about -1 kBq m(-3)  degrees
      C(-1) and that of the barometric pressure is -5 kBq m(-3) hPa(-1) in summer and 
      0.5 kBq m(-3) hPa(-1) in winter. In the high frequency range (>0.48 cpd) all
      regression coefficients are one order of magnitude smaller than in the range of
      0.072-0.48 cpd. Fast Fourier Transform of the radon concentration, temperature
      and barometric pressure time series revealed S1, K1, P1, S2, K2, M2 tidal
      constituents in the data and weak O1 components in the radon concentration and
      barometric pressure series. A detailed tidal analysis, however, showed that the
      radon tidal components are not directly driven by the gravitational force but
      rather by solar radiation and barometric tide. Principal Component Analysis of
      the raw data was performed to investigate the yearly, summer and winter
      variability of the radon concentration, temperature and barometric pressure. In
      the summer and winter periods the variability does not change. The higher
      variability of the radon concentration compared to the variability of the
      temperature and the barometric pressure shows that besides the temperature and
      barometric pressure variations other agents, e.g. natural ventilation of the
      observatory, wind, etc. also play an important role in the radon concentration
      variation.

PMID- 26207822
TI  - Handling the Dilemma of Self-Determination and Dementia: A Study of Case
      Managers' Discursive Strategies in Assessment Meetings.
AB  - In assessment meetings concerning care services for people with dementia, Swedish
      case managers face a dilemma. On the one hand, according to the law, the right to
      self-determination of every adult citizen must be respected, but on the other
      hand cognitive disabilities make it difficult to fulfill obligations of being a
      full-fledged citizen. In this article, we examine 15 assessment meetings to
      identify discursive strategies used by case managers to handle this dilemma. We
      also examine how these affect the participation of persons with dementia, and
      indicate implications of our study for social work practice and research. 

PMID- 26207823
TI  - Antimicrobial Nanoemulsion Formulation with Improved Penetration of Foliar Spray
      through Citrus Leaf Cuticles to Control Citrus Huanglongbing.
AB  - Huanglongbing (HLB) is the most serious disease affecting the citrus industry
      worldwide to date. The causal agent, Candidatus Liberibacter asiaticus (Las),
      resides in citrus phloem, which makes it difficult to effectively treat with
      chemical compounds. In this study, a transcuticular nanoemulsion formulation was
      developed to enhance the permeation of an effective antimicrobial compound
      (ampicillin; Amp) against HLB disease through the citrus cuticle into the phloem
      via a foliar spray. The results demonstrated that efficiency of cuticle isolation
      using an enzymatic method (pectinase and cellulase) was dependent on the citrus
      cultivar and Las-infection, and it was more difficult to isolate cuticles from
      valencia orange (Citrus sinensis) and HLB-symptomatic leaves. Of eight adjuvants
      tested, Brij 35 provided the greatest increase in permeability of the HLB
      affected cuticle with a 3.33-fold enhancement of cuticular permeability over
      water control. An in vitro assay using Bacillus subtilis showed that nanoemulsion
      formulations containing Amp (droplets size = 5.26 +/- 0.04 nm and 94 +/- 1.48 nm)
      coupled with Brij 35 resulted in greater inhibitory zone diameters (5.75 mm and
      6.66 mm) compared to those of Brij 35 (4.34 mm) and Amp solution (2.83 mm) alone.
      Furthermore, the nanoemulsion formulations eliminated Las bacteria in HLB
      affected citrus in planta more efficiently than controls. Our study shows that a
      water in oil (W/O) nanoemulsion formulation may provide a useful model for the
      effective delivery of chemical compounds into citrus phloem via a foliar spray
      for controlling citrus HLB. 

PMID- 26207824
TI  - Evolutionary and Taxonomic Implications of Variation in Nuclear Genome Size:
      Lesson from the Grass Genus Anthoxanthum (Poaceae).
AB  - The genus Anthoxanthum (sweet vernal grass, Poaceae) represents a taxonomically
      intricate polyploid complex with large phenotypic variation and its evolutionary
      relationships still poorly resolved. In order to get insight into the geographic
      distribution of ploidy levels and assess the taxonomic value of genome size data,
      we determined C- and Cx-values in 628 plants representing all currently
      recognized European species collected from 197 populations in 29 European
      countries. The flow cytometric estimates were supplemented by conventional
      chromosome counts. In addition to diploids, we found two low (rare 3x and common
      4x) and one high (~16x-18x) polyploid levels. Mean holoploid genome sizes ranged
      from 5.52 pg in diploid A. alpinum to 44.75 pg in highly polyploid A. amarum,
      while the size of monoploid genomes ranged from 2.75 pg in tetraploid A. alpinum
      to 9.19 pg in diploid A. gracile. In contrast to Central and Northern Europe,
      which harboured only limited cytological variation, a much more complex pattern
      of genome sizes was revealed in the Mediterranean, particularly in Corsica. Eight
      taxonomic groups that partly corresponded to traditionally recognized species
      were delimited based on genome size values and phenotypic variation. Whereas our
      data supported the merger of A. aristatum and A. ovatum, eastern Mediterranean
      populations traditionally referred to as diploid A. odoratum were shown to be
      cytologically distinct, and may represent a new taxon. Autopolyploid origin was
      suggested for 4x A. alpinum. In contrast, 4x A. odoratum seems to be an
      allopolyploid, based on the amounts of nuclear DNA. Intraspecific variation in
      genome size was observed in all recognized species, the most striking example
      being the A. aristatum/ovatum complex. Altogether, our study showed that genome
      size can be a useful taxonomic marker in Anthoxathum to not only guide taxonomic
      decisions but also help resolve evolutionary relationships in this challenging
      grass genus. 

PMID- 26207825
TI  - An Improvement of Pose Measurement Method Using Global Control Points
      Calibration.
AB  - During the last decade pose measurement technologies have gained an increasing
      interest in the computer vision. The vision-based pose measurement method has
      been widely applied in complex environments. However, the pose measurement error
      is a problem in the measurement applications. It grows rapidly with increasing
      measurement range. In order to meet the demand of high accuracy in large
      measurement range, a measurement error reduction solution to the vision-based
      pose measurement method, called Global Control Point Calibration (GCPC), is
      proposed. GCPC is an optimized process of existing visual pose measurement
      methods. The core of GCPC is to divide the measurement error into two types: the
      control point error and the control space error. Then by creating the global
      control points as well as performing error calibration of object pose, the two
      errors are processed. The control point error can be eliminated and the control
      space error is minimized. GCPC is experimented on the moving target in the
      camera's field of view. The results show that the RMS error is 0.175 degrees  in
      yaw angle, 0.189 degrees  in pitch angle, and 0.159 degrees  in roll angle, which
      demonstrate that GCPC works effectively and stably. 

PMID- 26207826
TI  - Correction: Evaluation of a push-pull approach for Aedes aegypti (L.) using a
      novel dispensing system for spatial repellents in the laboratory and in a semi
      field environment.

PMID- 26207827
TI  - Leptospirosis in Mexico: Epidemiology and Potential Distribution of Human Cases.
AB  - BACKGROUND: Leptospirosis is widespread in Mexico, yet the potential distribution
      and risk of the disease remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: We
      analysed morbidity and mortality according to age and gender based on three
      sources of data reported by the Ministry of Health and the National Institute of
      Geography and Statics of Mexico, for the decade 2000-2010. A total of 1,547 cases
      were reported in 27 states, the majority of which were registered during the
      rainy season, and the most affected age group was 25-44 years old. Although
      leptospirosis has been reported as an occupational disease of males, analysis of
      morbidity in Mexico showed no male preference. A total number of 198 deaths were
      registered in 21 states, mainly in urban settings. Mortality was higher in males
      (61.1%) as compared to females (38.9%), and the case fatality ratio was also
      increased in males. The overall case fatality ratio in Mexico was elevated
      (12.8%), as compared to other countries. We additionally determined the potential
      disease distribution by examining the spatial epidemiology combined with spatial
      modeling using ecological niche modeling techniques. We identified regions where
      leptospirosis could be present and created a potential distribution map using
      bioclimatic variables derived from temperature and precipitation. Our data show
      that the distribution of the cases was more related to temperature (75%) than to
      precipitation variables. Ecological niche modeling showed predictive areas that
      were widely distributed in central and southern Mexico, excluding areas
      characterized by extreme climates. CONCLUSIONS/SIGNIFICANCE: In conclusion, an
      epidemiological surveillance of leptospirosis is recommended in Mexico, since
      55.7% of the country has environmental conditions fulfilling the criteria that
      favor the presence of the disease.

PMID- 26207828
TI  - Predicted Shifts in Small Mammal Distributions and Biodiversity in the Altered
      Future Environment of Alaska: An Open Access Data and Machine Learning
      Perspective.
AB  - Climate change is acting to reallocate biomes, shift the distribution of species,
      and alter community assemblages in Alaska. Predictions regarding how these
      changes will affect the biodiversity and interspecific relationships of small
      mammals are necessary to pro-actively inform conservation planning. We used a set
      of online occurrence records and machine learning methods to create bioclimatic
      envelope models for 17 species of small mammals (rodents and shrews) across
      Alaska. Models formed the basis for sets of species-specific distribution maps
      for 2010 and were projected forward using the IPCC (Intergovernmental Panel on
      Climate Change) A2 scenario to predict distributions of the same species for
      2100. We found that distributions of cold-climate, northern, and interior small
      mammal species experienced large decreases in area while shifting northward,
      upward in elevation, and inland across the state. In contrast, many southern and
      continental species expanded throughout Alaska, and also moved down-slope and
      toward the coast. Statewide community assemblages remained constant for 15 of the
      17 species, but distributional shifts resulted in novel species assemblages in
      several regions. Overall biodiversity patterns were similar for both time frames,
      but followed general species distribution movement trends. Biodiversity losses
      occurred in the Yukon-Kuskokwim Delta and Seward Peninsula while the Beaufort
      Coastal Plain and western Brooks Range experienced modest gains in species
      richness as distributions shifted to form novel assemblages. Quantitative species
      distribution and biodiversity change projections should help land managers to
      develop adaptive strategies for conserving dispersal corridors, small mammal
      biodiversity, and ecosystem functionality into the future. 

PMID- 26207829
TI  - Identifying Subgroups among Hardcore Smokers: a Latent Profile Approach.
AB  - INTRODUCTION: Hardcore smokers are smokers who have little to no intention to
      quit. Previous research suggests that there are distinct subgroups among hardcore
      smokers and that these subgroups vary in the perceived pros and cons of smoking
      and quitting. Identifying these subgroups could help to develop individualized
      messages for the group of hardcore smokers. In this study we therefore used the
      perceived pros and cons of smoking and quitting to identify profiles among
      hardcore smokers. METHODS: A sample of 510 hardcore smokers completed an online
      survey on the perceived pros and cons of smoking and quitting. We used these
      perceived pros and cons in a latent profile analysis to identify possible
      subgroups among hardcore smokers. To validate the profiles identified among
      hardcore smokers, we analysed data from a sample of 338 non-hardcore smokers in a
      similar way. RESULTS: We found three profiles among hardcore smokers. 'Receptive'
      hardcore smokers (36%) perceived many cons of smoking and many pros of quitting.
      'Ambivalent' hardcore smokers (59%) were rather undecided towards quitting.
      'Resistant' hardcore smokers (5%) saw few cons of smoking and few pros of
      quitting. Among non-hardcore smokers, we found similar groups of 'receptive'
      smokers (30%) and 'ambivalent' smokers (54%). However, a third group consisted of
      'disengaged' smokers (16%), who saw few pros and cons of both smoking and
      quitting. DISCUSSION: Among hardcore smokers, we found three distinct profiles
      based on perceived pros and cons of smoking. This indicates that hardcore smokers
      are not a homogenous group. Each profile might require a different tobacco
      control approach. Our findings may help to develop individualized tobacco control
      messages for the particularly hard-to-reach group of hardcore smokers.

PMID- 26207830
TI  - Notch3-specific inhibition using siRNA knockdown or GSI sensitizes paclitaxel
      resistant ovarian cancer cells.
AB  - Notch signaling plays an important role in ovarian cancer chemoresistance, which
      is responsible for recurrence. Gamma-secretase inhibitor (GSI) is a broad
      spectrum Notch inhibitor, but it has serious side effects. The efficacy of Notch3
      specific inhibition in paclitaxel-resistant ovarian cancers was assessed in this
      study, which has not yet been evaluated relative to GSI. To analyze the effect of
      Notch3-specific inhibition on paclitaxel-resistant ovarian cancers, we compared
      cell viability, apoptosis, cell migration, angiogenesis, cell cycle, and spheroid
      formation after treatment with either Notch3 siRNA or GSI in paclitaxel-resistant
      SKpac cells and parental SKOV3 cells. Expression levels of survival, cell cycle,
      and apoptosis-related proteins were measured and compared between groups. Notch3
      was significantly overexpressed in chemoresistant cancer tissues and cell lines
      relative to chemosensitive group. In paclitaxel-resistant cancer cells, Notch
      inhibition significantly reduced viability, migration, and angiogenesis and
      increased apoptosis, thereby boosting sensitivity to paclitaxel. Spheroid
      formation was also significantly reduced. Both Notch3 siRNA-treated cells and GSI
      treated cells arrested in the G2/M phase of the cell cycle. Proteins of cell
      survival, cyclin D1 and cyclin D3 were reduced, whereas p21 and p27 were
      elevated. Both GSI and Notch3 siRNA treatment reduced expression of anti
      apoptotic proteins (BCL-W, BCL2, and BCL-XL) and increased expression of pro
      apoptotic proteins (Bad, Bak, Bim, Bid, and Bax). These results indicate that
      Notch3-specific inhibition sensitizes paclitaxel-resistant cancer cells to
      paclitaxel treatment, with an efficacy comparable to that of GSI. This approach
      would be likely to avoid the side effects of broad-spectrum GSI treatment. (c)
      2015 Wiley Periodicals, Inc.

PMID- 26207832
TI  - A Novel Intravital Imaging Window for Longitudinal Microscopy of the Mouse Ovary.
AB  - The ovary is a dynamic organ that undergoes dramatic remodeling throughout the
      ovulatory cycle. Maturation of the ovarian follicle, release of the oocyte in the
      course of ovulation as well as formation and degradation of corpus luteum involve
      tightly controlled remodeling of the extracellular matrix and vasculature.
      Ovarian tumors, regardless of their tissue of origin, dynamically interact with
      the ovarian microenvironment. Their activity in the tissue encompasses
      recruitment of host stroma and immune cells, attachment of tumor cells to
      mesothelial layer, degradation of the extracellular matrix and tumor cell
      migration. High-resolution dynamic imaging of such processes is particularly
      challenging for internal organs. The implementation of a novel imaging window as
      reported here enabled longitudinal microscopy of ovarian physiology and
      orthotopic tumor invasion. 

PMID- 26207831
TI  - BTB-Zinc Finger Oncogenes Are Required for Ras and Notch-Driven Tumorigenesis in
      Drosophila.
AB  - During tumorigenesis, pathways that promote the epithelial-to-mesenchymal
      transition (EMT) can both facilitate metastasis and endow tumor cells with cancer
      stem cell properties. To gain a greater understanding of how these properties are
      interlinked in cancers we used Drosophila epithelial tumor models, which are
      driven by orthologues of human oncogenes (activated alleles of Ras and Notch) in
      cooperation with the loss of the cell polarity regulator, scribbled (scrib).
      Within these tumors, both invasive, mesenchymal-like cell morphology and
      continual tumor overgrowth, are dependent upon Jun N-terminal kinase (JNK)
      activity. To identify JNK-dependent changes within the tumors we used a
      comparative microarray analysis to define a JNK gene signature common to both Ras
      and Notch-driven tumors. Amongst the JNK-dependent changes was a significant
      enrichment for BTB-Zinc Finger (ZF) domain genes, including chronologically
      inappropriate morphogenesis (chinmo). chinmo was upregulated by JNK within the
      tumors, and overexpression of chinmo with either RasV12 or Nintra was sufficient
      to promote JNK-independent epithelial tumor formation in the eye/antennal disc,
      and, in cooperation with RasV12, promote tumor formation in the adult midgut
      epithelium. Chinmo primes cells for oncogene-mediated transformation through
      blocking differentiation in the eye disc, and promoting an escargot-expressing
      stem or enteroblast cell state in the adult midgut. BTB-ZF genes are also
      required for Ras and Notch-driven overgrowth of scrib mutant tissue, since,
      although loss of chinmo alone did not significantly impede tumor development,
      when loss of chinmo was combined with loss of a functionally related BTB-ZF gene,
      abrupt, tumor overgrowth was significantly reduced. abrupt is not a JNK-induced
      gene, however, Abrupt is present in JNK-positive tumor cells, consistent with a
      JNK-associated oncogenic role. As some mammalian BTB-ZF proteins are also highly
      oncogenic, our work suggests that EMT-promoting signals in human cancers could
      similarly utilize networks of these proteins to promote cancer stem cell states. 

PMID- 26207834
TI  - Candidatus Neoehrlichia mikurensis in Ticks from Migrating Birds in Sweden.
AB  - Candidatus Neoehrlichia mikurensis (CNM; family Anaplasmataceae) was recently
      recognized as a potential tick-borne human pathogen. The presence of CNM in
      mammals, in host-seeking Ixodes ticks and in ticks attached to mammals and birds
      has been reported recently. We investigated the presence of CNM in ornithophagous
      ticks from migrating birds. A total of 1,150 ticks (582 nymphs, 548 larvae, 18
      undetermined ticks and two adult females) collected from 5,365 birds captured in
      south-eastern Sweden was screened for CNM by molecular methods. The birds
      represented 65 different species, of which 35 species were infested with one or
      more ticks. Based on a combination of morphological and molecular species
      identification, the majority of the ticks were identified as Ixodes ricinus.
      Samples were initially screened by real-time PCR targeting the CNM 16S rRNA gene,
      and confirmed by a second real-time PCR targeting the groEL gene. For positive
      samples, a 1260 base pair fragment of the 16S rRNA gene was sequenced. Based upon
      bacterial gene sequence identification, 2.1% (24/1150) of the analysed samples
      were CNM-positive. Twenty-two out of 24 CNM-positive ticks were molecularly
      identified as I. ricinus nymphs, and the remaining two were identified as I.
      ricinus based on morphology. The overall CNM prevalence in I. ricinus nymphs was
      4.2%. None of the 548 tested larvae was positive. CNM-positive ticks were
      collected from 10 different bird species. The highest CNM-prevalences were
      recorded in nymphs collected from common redpoll (Carduelis flammea, 3/7), thrush
      nightingale (Luscinia luscinia, 2/29) and dunnock (Prunella modularis, 1/17). The
      16S rRNA sequences obtained in this study were all identical to each other and to
      three previously reported European strains, two of which were obtained from
      humans. It is concluded that ornithophagous ticks may be infected with CNM and
      that birds most likely can disperse CNM-infected ticks over large geographical
      areas. 

PMID- 26207833
TI  - Partial Hepatectomy Induced Long Noncoding RNA Inhibits Hepatocyte Proliferation
      during Liver Regeneration.
AB  - Liver regeneration after partial hepatectomy (PHx) is a complex and well
      orchestrated biological process in which synchronized cell proliferation is
      induced in response to the loss of liver mass. To define long noncoding RNAs
      (lncRNAs) that participate in the regulation of liver regeneration, we performed
      microarray analysis and identified more than 400 lncRNAs exhibiting significantly
      altered expression. Of these, one lncRNA, LncPHx2 (Long noncoding RNA induced by
      PHx 2), was highly upregulated during liver regeneration. Depletion of LncPHx2
      during liver regeneration using antisense oligonucleotides led to a transient
      increase in hepatocyte proliferation and more rapid liver regeneration. Gene
      expression analysis showed that LncPHx2 depletion resulted in upregulation of
      mRNAs encoding proteins known to promote cell proliferation, including MCM
      components, DNA polymerases, histone proteins, and transcription factors. LncPHx2
      interacts with the mRNAs of MCM components, making it a candidate to regulate the
      expression of MCMs and other genes post-transcriptionally. Collectively, our data
      demonstrate that LncPHx2 is a key lncRNA that participates in a negative feedback
      loop modulating hepatocyte proliferation through RNA-RNA interactions. 

PMID- 26207839
TI  - Multicolored, Tb3+-Based Antibody-Free Detection of Multiple Tyrosine Kinase
      Activities.
AB  - Kinase signaling is a major mechanism driving many cancers. While many inhibitors
      have been developed and are employed in the clinic, resistance due to crosstalk
      and pathway reprogramming is an emerging problem. High-throughput assays to
      detect multiple pathway kinases simultaneously could better model these complex
      relationships and enable drug development to combat this type of resistance. We
      developed a strategy to take advantage of time-resolved luminescence of Tb(3+)
      chelated phosphotyrosine-containing peptides, which facilitated efficient energy
      transfer to small molecule fluorophores conjugated to the peptides to produce
      orthogonally colored biosensors for two different kinases. This enabled
      multiplexed detection with high signal-to-noise in a high-throughput-compatible
      format. This proof-of-concept study provides a platform that could be applied to
      other lanthanide metal and fluorophore combinations to achieve even greater
      multiplexing without the need for phosphospecific antibodies. 

PMID- 26207840
TI  - beta-Hydroxydihydrochalcone and flavonoid glycosides along with triterpene
      saponin and sesquiterpene from the herbs of Pimpinella rhodantha Boiss.
AB  - A new beta-hydroxydihydrochalcone glycoside named ziganin (1) and a new acylated
      flavonol glycoside named isorhamnetin-3-O-alpha-L-(2",3"-di-O-trans-coumaroyl)
      rhamnopyranoside) (2), along with two known flavonoid glycosides, a beta
      hydroxydihydrochalcone glycoside, a hydroxybenzoic acid derivative, a
      trinorguaiane type sesquiterpenoid, a triterpenic saponin and a polyol were
      isolated from the herbs of Pimpinella rhodantha Boiss. Their structures were
      elucidated on the basis of spectroscopic analyses including 1D-and 2D-NMR, UV,
      IR, CD, ESI-MS, APCI-MS, HR-ESI-MS techniques. The isolated compounds were
      evaluated for their antioxidant capacity through the DPPH free-radical scavenging
      assay and ferrous ion-chelating power test. 

PMID- 26207841
TI  - Control of Electron Beam-Induced Au Nanocrystal Growth Kinetics through Solution
      Chemistry.
AB  - Measurements of solution-phase crystal growth provide mechanistic information
      that is helpful in designing and synthesizing nanostructures. Here, we examine
      the model system of individual Au nanocrystal formation within a defined liquid
      geometry during electron beam irradiation of gold chloride solution, where
      radiolytically formed hydrated electrons reduce Au ions to solid Au. By selecting
      conditions that favor the growth of well-faceted Au nanoprisms, we measure growth
      rates of individual crystals. The volume of each crystal increases linearly with
      irradiation time at a rate unaffected by its shape or proximity to neighboring
      crystals, implying a growth process that is controlled by the arrival of atoms
      from solution. Furthermore, growth requires a threshold dose rate, suggesting
      competition between reduction and oxidation processes in the solution. Above this
      threshold, the growth rate follows a power law with dose rate. To explain the
      observed dose rate dependence, we demonstrate that a reaction-diffusion model is
      required that explicitly accounts for the species H(+) and Cl(-). The model
      highlights the necessity of considering all species present when interpreting
      kinetic data obtained from beam-induced processes, and suggest conditions under
      which growth rates can be controlled with higher precision. 

PMID- 26207842
TI  - Can one communication module assess all aspects of communication?

PMID- 26207846
TI  - Correction: Generation of a Transcriptome in a Model Lepidopteran Pest, Heliothis
      virescens, Using Multiple Sequencing Strategies for Profiling Midgut Gene
      Expression.

PMID- 26207847
TI  - Urodynamics for incontinence after midurethral sling removal.
AB  - INTRODUCTION: We reviewed the role of urodynamics (UDS) in the management of
      women with incontinence following mid-urethral sling removal (MUSR). METHODS:
      Following IRB approval, women from a longitudinal database who had persistent or
      recurrent urinary incontinence (UI) after MUSR, desired further therapy, and
      subsequently underwent UDS were reviewed. Women with neurogenic bladder,
      obstructive symptoms without UI, urethra-vaginal fistula, anterior compartment
      prolapse >Stage 2, or those who had concomitant autologous sling surgery at the
      time of MUSR were excluded. Interval time between MUSR and UDS, UDS findings, and
      UI management after UDS were recorded. RESULTS: From 2006 to 2013, 71 of 246
      women had UDS after MUSR for persistent or recurrent UI. For the 54 women in the
      final analysis, mean time between tape removal and UDS was 12.4 months (range: 4
      65). UDS demonstrated incontinence in 78% of patients: stress urinary
      incontinence (SUI) in 19 (35%), detrusor overactivity incontinence (DOI) in 6
      (11%), and mixed urinary incontinence (MUI) in 17 (32%). On pressure-flow
      studies, the following voiding patterns were demonstrated: normal voiding (39),
      valsalva voiding (6), obstruction (2), underactive detrusor (1), no voiding
      records (6). UDS storage and emptying data were used in subsequent symptom-based
      patient counseling for treatment planning. Urethral bulking agent was the most
      commonly chosen management (43%). CONCLUSION: Our current guidelines for UDS in
      women after incontinence procedures and MUSR are currently based on a low level
      of evidence. This study reinforces the role of UDS to guide therapy for UI after
      MUSR. Neurourol. Urodynam. 35:939-943, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26207848
TI  - A New Targeted Model of Experimental Autoimmune Encephalomyelitis in the Common
      Marmoset.
AB  - Multiple sclerosis (MS) is the most common cause for sustained disability in
      young adults, yet treatment options remain very limited. Although numerous
      therapeutic approaches have been effective in rodent models of experimental
      autoimmune encephalomyelitis (EAE), only few proved to be beneficial in patients
      with MS. Hence, there is a strong need for more predictive animal models. Within
      the past decade, EAE in the common marmoset evolved as a potent, alternative
      model for MS, with immunological and pathological features resembling more
      closely the human disease. However, an often very rapid and severe disease course
      hampers its implementation for systematic testing of new treatment strategies. We
      here developed a new focal model of EAE in the common marmoset, induced by myelin
      oligodendrocyte glycoprotein (MOG) immunization and stereotactic injections of
      proinflammatory cytokines. At the injection site of cytokines, confluent
      inflammatory demyelinating lesions developed that strongly resembled human MS
      lesions. In a proof-of-principle treatment study with the immunomodulatory
      compound laquinimod, we demonstrate that targeted EAE in marmosets provides a
      promising and valid tool for preclinical experimental treatment trials in MS
      research.

PMID- 26207849
TI  - Age-related factor IX correction in symptomatic female carriers with haemophilia
      B Leyden.

PMID- 26207850
TI  - Diminishing Returns or Compounding Benefits of Air Pollution Control? The Case of
      NOx and Ozone.
AB  - A common measure used in air quality benefit-cost assessment is marginal benefit
      (MB), or the monetized societal benefit of reducing 1 ton of emissions.
      Traditional depictions of MB for criteria air pollutants are such that each
      additional ton of emission reduction incurs less benefit than the previous ton.
      Using adjoint sensitivity analysis in a state-of-the-art air quality model, we
      estimate MBs for NOx emitted from mobile and point sources, characterized based
      on the estimated ozone-related premature mortality in the U.S. POPULATION: Our
      findings indicate that nation-wide emission reductions in the U.S. significantly
      increase NOx MBs for all sources, without exception. We estimate that MBs for NOx
      emitted from mobile sources increase by 1.5 and 2.5 times, on average, for 40%
      and 80% reductions in anthropogenic emissions across the U.S. Our results
      indicate a strictly concave damage function and compounding benefits of
      progressively lower levels of NOx emissions, providing economic incentive for
      higher levels of abatement than were previously advisible. These findings suggest
      that the traditional perception of a convex damage function and decreasing MB
      with abatement may not hold true for secondary pollutants such as O3.

PMID- 26207851
TI  - Innovations in the systematic review of text and opinion.
AB  - BACKGROUND: Evidence-based healthcare focuses on the need to use interventions
      that are supported by the best available and most up-to-date evidence or
      knowledge. Many clinical questions cannot be fully answered by evidence derived
      from quantitative or qualitative research designs alone, since many areas in
      healthcare are supported by clinicians' tacit knowledge derived from their
      clinical experiences. In this situation, evidence generated from a systematic
      review of text and opinion may be required as the best available evidence. The
      aim of this study is to highlight the importance and role of expert opinion
      synthesis in healthcare, and present results of an international methodological
      group review. METHODS: A methodological group was formed to review this approach,
      and update the guidance and processes for undertaking a systematic review of text
      and opinion. RESULTS: The methodology of systematic reviews of text and opinion
      had already been developed by the Joanna Briggs Institute. We reviewed and
      updated several steps in the process, such as inclusion criteria, search
      strategy, critical appraisal and data extraction. CONCLUSIONS: The Joanna Briggs
      Institute methodology for the systematic review of text and opinion is unique,
      and continuously evolving and being further developed. Systematic reviews of text
      and opinion may be considered as legitimate sources of evidence, especially when
      there is an absence of other research designs.

PMID- 26207853
TI  - Endorsement of the CONSORT Principles in Reporting Alcohol Clinical Trials in
      ACER.

PMID- 26207852
TI  - Inhibition of Advanced Glycation Endproduct Formation by Lotus Seedpod Oligomeric
      Procyanidins through RAGE-MAPK Signaling and NF-kappaB Activation in High-Fat
      Diet Rats.
AB  - This study investigated the protective properties of lotus seedpod oligomeric
      procyanidins (LSOPC) against nonalcoholic fatty liver disease (NAFLD) and its
      underlying mechanism. Sprague-Dawley (SD) male rats were fed a basic diet, a high
      fat diet (HFD), or HFD plus 0.2 or 0.5% (w/w) LSOPC for 12 weeks. Administration
      of LSOPC markedly reduced serum and hepatic biochemical parameters and protein
      expression of advanced glycation endproducts (AGEs). Additionally, 0.5% (w/w)
      LSOPC treatment remarkably reversed the increasing tendency of receptor of
      advanced glycation endproduct (RAGE) to normal level. Furthermore, dietary LSOPC
      significantly decreased the protein levels of mitogen-activated protein kinases
      (MAPK) and nuclear factor-kappa B (NF-kappaB) and down-regulated genes involved
      in pro-inflammatory cytokines and adhesion molecules. Taken together, these
      findings demonstrate that LSOPC may protect obese rats with long-term HFD-induced
      NAFLD against RAGE-MAPK-NF-kappaB signaling suppression. 

PMID- 26207854
TI  - Neurotoxicity of common peripheral nerve block adjuvants.
AB  - PURPOSE OF REVIEW: This review outlines the analgesic role of perineural
      adjuvants for local anesthetic nerve block injections, and evaluates current
      knowledge regarding whether adjuvants modulate the neurocytologic properties of
      local anesthetics. RECENT FINDINGS: Perineural adjuvant medications such as
      dexmedetomidine, clonidine, buprenorphine, dexamethasone, and midazolam play
      unique analgesic roles. The dosing of these medications to prevent neurotoxicity
      is characterized in various cellular and in-vivo models. Much of this mitigation
      may be via reducing the dose of local anesthetic used while achieving equal or
      superior analgesia. Dose-concentration animal models have shown no evidence of
      deleterious effects. Clinical observations regarding blocks with combined
      bupivacaine-clonidine-buprenorphine-dexamethasone have shown beneficial effects
      on block duration and rebound pain without long-term evidence of neurotoxicity.
      In-vitro and in-vivo studies of perineural clonidine and dexmedetomidine show
      attenuation of perineural inflammatory responses generated by local anesthetics.
      SUMMARY: Dexmedetomidine added as a peripheral nerve blockade adjuvant improves
      block duration without neurotoxic properties. The combined adjuvants clonidine,
      buprenorphine, and dexamethasone do not appear to alter local anesthetic
      neurotoxicity. Midazolam significantly increases local anesthetic neurotoxicity
      in vitro, but when combined with clonidine-buprenorphine-dexamethasone (sans
      local anesthetic) produces no in-vitro or in-vivo neurotoxicity. Further larger
      species animal testing and human trials will be required to reinforce the
      clinical applicability of these findings.

PMID- 26207855
TI  - Anti-inflammatory effects of grape seed procyanidin B2 on a diabetic pancreas.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) has increased considerably in
      recent years, highlighting the importance of developing new therapeutic
      strategies. Insulin-resistance and gradual dysfunction of pancreatic islets are
      the mainstay in the progression of T2DM. Therefore, preserving the function of
      the pancreas may lead to new prospective approaches. Our previous studies
      suggested that grape seed procyanidin B2 (GSPB2), a natural polyphenol product,
      exhibited protective effects on diabetic vasculopathy. However, effects of GSPB2
      on a diabetic pancreas remain unknown. In this study, we provided strong evidence
      that GSPB2 exerted protective effects on a diabetic pancreas. GSPB2 attenuated
      the elevated body weights, food intake and advanced glycation end-product (AGE)
      levels in db/db mice (p < 0.05), though it had no significant effect on glucose
      levels. The increased islet sizes, insulin levels, as well as HOMA-IR were also
      improved by GSPB2 treatment in db/db mice (p < 0.05). Milk fat globule epidermal
      growth factor-8 (MFG-E8), an estimated target of GSPB2 in our previous studies,
      was up-regulated in pancreatic tissues whereas GSPB2 treatment down-regulated the
      protein level (p < 0.05). Since MFG-E8 is highly involved in inflammation, we
      further investigate pro-inflammatory cytokines interleukin-1beta (IL-1beta) and
      NLRP3 levels. We found that levels of IL-1beta and NLRP3 increased in a diabetic
      pancreas while GSPB2 treatment notably attenuated these alterations (p < 0.05).
      In conclusion, our results suggest that inflammation is involved in the damage of
      a diabetic pancreas and GSPB2 provides protective effects at least in part
      through anti-inflammation. 

PMID- 26207857
TI  - Palladium-catalyzed cross-coupling of aryl fluorides with N-tosylhydrazones via C
      F bond activation.
AB  - A palladium-catalyzed cross-coupling reaction of electron-deficient aryl
      fluorides with aryl N-tosylhydrazones has been reported. Mechanistically, this
      approach involves C-F bond activation and migratory insertion of palladium
      carbene as the two key steps. 

PMID- 26207856
TI  - A Longitudinal Examination of the Associations Between Shyness, Drinking Motives,
      Alcohol Use, and Alcohol-Related Problems.
AB  - BACKGROUND: The current study evaluated the roles of drinking motives and shyness
      in predicting problem alcohol use over 2 years. METHODS: First-year college
      student drinkers (n = 818) completed assessments of alcohol use and related
      problems, shyness, and drinking motives every 6 months over a 2-year period.
      RESULTS: Generalized linear mixed models indicated that shyness was associated
      with less drinking, but more alcohol-related problems. Further, shyness was
      associated with coping, conformity, and enhancement drinking motives, but was not
      associated with social drinking motives. However, when examining coping motives,
      moderation analyses revealed that social drinking motives were more strongly
      associated with coping motives among individuals higher in shyness. In addition,
      coping, conformity, and enhancement motives, but not social motives, mediated
      associations between shyness and alcohol-related problems over time. Finally,
      coping motives mediated the association between the interaction of shyness and
      social motives and alcohol-related problems. CONCLUSIONS: Together, the results
      suggest that shy individuals may drink to reduce negative affect, increase
      positive affect, and fit in with others in social situations, which may then
      contribute to greater risk for subsequent alcohol-related problems.

PMID- 26207858
TI  - A selective decoy-doxorubicin complex for targeted co-delivery, STAT3 probing and
      synergistic anti-cancer effect.
AB  - A novel selective decoy oligodeoxynucleotide (dODN)-doxorubicin (DOX) complex is
      reported for cancer theranostics. It eliminates the use of a ligand or carrier
      for targeted delivery and disassembles into therapeutic dODN and DOX upon
      encountering over-activated STAT3 in cancer cells. Hence, in situ STAT3 probing
      and synergistic anti-cancer effect are attained at the same time. 

PMID- 26207859
TI  - Membrane fluidity in the center of fever-enhanced immunity.

PMID- 26207860
TI  - Response to Comment on "Appalachian Mountaintop Mining Particulate Matter Induces
      Neoplastic Transformation of Human Bronchial Epithelial Cells and Promotes Tumor
      Formation".

PMID- 26207861
TI  - Discovering Hannelore Wass.
AB  - As a strong proponent of death education, Dr. Hannelore Wass was a respected
      pioneer in the field of thanatology. She had a philosophy that, in order to
      effectively work with grieving children and adolescents, one must be like and
      think like a child; indeed, to see things through the eyes of a child. This
      article demonstrates the far-reaching effects of Wass's work beyond her students
      to another generation of educators. 

PMID- 26207862
TI  - High-Performance Olivine NaFePO4 Microsphere Cathode Synthesized by Aqueous
      Electrochemical Displacement Method for Sodium Ion Batteries.
AB  - Olivine NaFePO4/C microsphere cathode is prepared by a facile aqueous
      electrochemical displacement method from LiFePO4/C precursor. The NaFePO4/C
      cathode shows a high discharge capacity of 111 mAh g(-1), excellent cycling
      stability with 90% capacity retention over 240 cycles at 0.1 C, and high rate
      capacity (46 mAh g(-1) at 2 C). The excellent electrochemical performance
      demonstrates that the aqueous electrochemical displacement method is an effective
      and promising way to prepare NaFePO4/C material for Na-based energy storage
      applications. Moreover, the Na2/3FePO4 intermediate is observed for the first
      time during the Na intercalation process through conventional electrochemical
      techniques, corroborating an identical two-step phase transition reaction both
      upon Na intercalation and deintercalation processes. The clarification of the
      electrochemical reaction mechanism of olivine NaFePO4 could inspire more
      attention on the investigation of this material for Na ion batteries. 

PMID- 26207864
TI  - ?

PMID- 26207863
TI  - ?

PMID- 26207865
TI  - ?

PMID- 26207866
TI  - ?

PMID- 26207867
TI  - TNF-alpha Production by Peripheral Blood Monocytes in Multiple Sclerosis Patients
      and Healthy Controls.
AB  - BACKGROUND: Aberrant immune responses are evident in the pathogenesis of multiple
      sclerosis (MS) and it has been proposed that the spectrum of cytokines influence
      disease outcomes. Leptin and lipopolysaccharide (LPS) of Gram-negative bacteria
      are both potent cellular stimulators for production of pro-inflammatory cytokines
      such as tumor necrosis factor-alpha (TNF-alpha). The aim of this study was to
      compare the TNF-alpha production by peripheral blood monocytes from MS patients
      with healthy controls. METHODS: Peripheral blood samples were stimulated with LPS
      or leptin. After blocking the Golgi apparatus, intracellular cytokine production
      was assessed using a monoclonal antibody against human TNF-alpha by the flow
      cytometry technique. Moreover, plasma level measurement of cytokines was
      performed using enzyme-linked immunosorbent assay (ELISA). RESULTS: Intracellular
      levels of TNF-alpha were 16.80 +/- 8.21 and 16.52 +/- 8.23in MS patients and
      healthy controls which showed no statistically significant difference between
      them (p = 0.850). Leptin-stimulated and LPS-stimulated TNF-alpha production
      showed no significant difference between MS patients and the control group (p =
      0.263 and p = 0.191, respectively). However, after treatment with leptin, a weak
      significant difference was shown between cases and control group (p = 0.049).
      There were significant differences between cases and controls regarding serum
      levels of IL-6 and Toll-like receptor-4 (TLR-4) before and after stimulation with
      leptin and LPS, separately (p < 0.05). CONCLUSION: Taken together, we cannot
      definitely conclude that TNF-alpha does not play an important role in
      pathogenesis of MS. However, other characteristics of monocyte activation such as
      IL-6 or TLRs can elucidate implication of peripheral blood monocytes in MS
      pathogenesis.

PMID- 26207868
TI  - Psychological factors are associated with subjective cognitive complaints 2
      months post-stroke.
AB  - The aim of this study was to investigate which psychological factors are related
      to post-stroke subjective cognitive complaints, taking into account the influence
      of demographic and stroke-related characteristics, cognitive deficits and
      emotional problems. In this cross-sectional study, 350 patients were assessed at
      2 months post-stroke, using the Checklist for Cognitive and Emotional
      consequences following stroke (CLCE-24) to identify cognitive complaints.
      Psychological factors were: proactive coping, passive coping, self-efficacy,
      optimism, pessimism, extraversion, and neuroticism. Associations between CLCE-24
      cognition score and psychological factors, emotional problems (depressive
      symptoms and anxiety), cognitive deficits, and demographic and stroke
      characteristics were examined using Spearman correlations and multiple regression
      analyses. Results showed that 2 months post-stroke, 270 patients (68.4%) reported
      at least one cognitive complaint. Age, sex, presence of recurrent stroke(s),
      comorbidity, cognitive deficits, depressive symptoms, anxiety, and all
      psychological factors were significantly associated with the CLCE-24 cognition
      score in bivariate analyses. Multiple regression analysis showed that
      psychological factors explained 34.7% of the variance of cognitive complaints
      independently, and 8.5% (p < .001) after taking all other factors into account.
      Of all psychological factors, proactive coping was independently associated with
      cognitive complaints (p < .001), showing that more proactive coping related to
      less cognitive complaints. Because cognitive complaints are common after stroke
      and are associated with psychological factors, it is important to focus on these
      factors in rehabilitation programmes.

PMID- 26207869
TI  - Decolorization and biodegradation of the Congo red by Acinetobacter baumannii
      YNWH 226 and its polymer production's flocculation and dewatering potential.
AB  - The strain Acinetobacter baumannii YNWH 226 was utilized to degrade Congo red
      (CR) under aerobic conditions. CR was employed as the sole carbon source to
      produce extracellular polymeric substances (EPS) used as potent bioflocculants in
      this strain. A total of 98.62% CR was removed during the 48-h decoloration
      experiments using CR (100 mg/L). A total of 83% bioadsorption and 65%
      biodegradation were responsible for the decoloration and degradation of CR
      through the strain. The bioflocculant showed high flocculation activity and
      dewaterability on textile dyeing sludge. A maximum flocculation of 78.62% with a
      minimum SBF of 3.07*10(9) s(2)/g and a CST of 58.4 s were achieved. We
      investigated the internal relationship between the decolorization efficiency of
      YNWH 226 and the flocculation activity and dewatering capacity of its EPS. The
      components and structure of the EPS highly influenced the decolorization
      efficiency of CR and the flocculation activity and dewatering capacity on sludge.

PMID- 26207870
TI  - Effects of substrate concentration on methane potential and degradation kinetics
      in batch anaerobic digestion.
AB  - In this study, two experiments were conducted to evaluate the impact of substrate
      concentrations on methane potential and degradation kinetics of substrate. The
      biochemical methane potential (BMP) tests in Experiment I were performed at a
      constant inoculum to substrate ratio (ISR), whereas, different ISRs were applied
      in Experiment II. Results obtained from Experiment I revealed that methane
      potential of substrate increased at a saturating trend with higher substrate
      concentrations, and could differ by up to 30% between the lowest and highest
      investigated concentrations. The results of Experiment II verified the results of
      Experiment I, and further showed that this trend also occurs when the substrate
      concentration is regulated with ISRs. In contrast, substrate concentration had no
      significant impact on the degradation kinetics. It was concluded that dilutions
      should be avoided when the substrate concentration is lower than 10 g VS/L in
      order to avoid underestimations of methane potential from BMP test.

PMID- 26207871
TI  - Degradation of corn stover by fungal cellulase cocktail for production of
      polyhydroxyalkanoates by moderate halophile Paracoccus sp. LL1.
AB  - Bioprocessing of lignocellulose as a renewable resource for fuels, chemicals or
      value added products is a necessity to fulfil demands of petroleum products. This
      study aims to convert corn stover to polyhydroxyalkanoates (PHA). Corn stover was
      hydrolyzed to crude sugars by an on-site prepared cellulase cocktail from co
      culture of Trichoderma reesei and Aspergillus niger. The potent PHA producer,
      Paracoccus sp. LL1, was isolated from Lonar Lake, India and could accumulate PHA
      up to 72.4% of its dry cell weight. PHA production reached 9.71 g/L from corn
      stover hydrolysate containing 40 g/L sugar mixture. The PHA synthase gene (phaC)
      sequence of the isolate showed 79% identity with the phaC gene of Paracoccus
      seriniphilus (E71) strain from the NCBI database. The nature/type of PHA was
      found to be poly(3-hydroxybutyrate) by Fourier transform infrared spectroscopy.

PMID- 26207872
TI  - Persistence of the benefit of an antioxidant therapy in children and teenagers
      with Down syndrome.
AB  - This study examined the effect of an antioxidant intervention in biomarkers of
      inflammation and oxidative stress (OS) in the blood of Down syndrome (DS)
      children and teenagers during four different stages. A control group was composed
      by healthy children (n=18), assessed once, and a Down group composed by DS
      patients (n=21) assessed at the basal period (t0), as well as after 6 months of
      antioxidant supplementation (t1), after 12 months (after interruption of the
      antioxidant intervention for 6 months) (t2), and again after further 6 months of
      antioxidant supplementation (t3). Biomarkers of inflammation (myeloperoxidase
      activity - MPO and levels of IL-1beta and TNF-alpha) and OS (thiobarbituric acid
      reactive substances - TBARS, protein carbonyls - PC), reduced glutathione (GSH),
      uric acid (UA) and vitamin E levels, as well as antioxidant enzymes such as
      superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GPx),
      glutathione reductase (GR), glutathione-S-transferase (GST) and gamma
      glutamyltransferase (GGT) activities, were measured after each period. After the
      antioxidant supplementation, the activities of SOD, CAT, GPx, GR, GGT and MPO
      were downregulated, while TBARS contents were strongly decreased, the contents of
      GSH and vitamin E were significantly increased, and no changes in G6PD and GST
      activity as well as in UA and PC levels were detected. After the interruption of
      the antioxidant therapy for 6 months, DS patients showed elevated GPx and GGT
      activities and also elevated UA and TBARS levels. No changes in SOD, CAT, GR,
      GST, G6PD and MPO activities as well as in GSH, vitamin E, PC, TNF-alpha and IL
      1beta levels were detected. The results showed that the antioxidant intervention
      persistently attenuated the systemic oxidative damage in DS patients even after a
      relatively long period of cessation of the antioxidant intervention. 

PMID- 26207874
TI  - Lipidomic differentiation between human kidney tumors and surrounding normal
      tissues using HILIC-HPLC/ESI-MS and multivariate data analysis.
AB  - The characterization of differences among polar lipid classes in tumors and
      surrounding normal tissues of 20 kidney cancer patients is performed by
      hydrophilic interaction liquid chromatography (HILIC) coupled to electrospray
      ionization mass spectrometry (ESI-MS). The detailed analysis of identified lipid
      classes using relative abundances of characteristic ions in negative- and
      positive-ion modes is used for the determination of more than 120 individual
      lipid species containing attached fatty acyls of different chain length and
      double bond number. Lipid species are described using relative abundances,
      providing a better visualization of lipidomic differences between tumor and
      normal tissues. The multivariate data analysis methods using unsupervised
      principal component analysis (PCA) and supervised orthogonal partial least square
      (OPLS) are used for the characterization of statistically significant differences
      in identified lipid species. Ten most significant up- and down-regulated lipids
      in OPLS score plots are also displayed by box plots. A notable increase of
      relative abundances of lipids containing four and more double bonds is detected
      in tumor compared to normal tissues. 

PMID- 26207873
TI  - The activity of propolis in the scavenging of vitamin B2-photogenerated ROS.
AB  - OBJECTIVES: The study was focused on the activity of propolis from Amaicha del
      Valle, Argentina (ProAV) as a promoter and scavenger of Riboflavin (Rf)-
      photogenerated reactive oxygen species (ROS). METHODS: Through a kinetic and
      mechanistic study, employing stationary and time-resolved photochemical and
      electrochemical techniques, the protecting activity of ProAV was investigated.
      RESULTS: In the absence of light and Rf, ProAV exerted a relatively efficient
      inhibitory effect on 1,1-diphenyl-2-picrylhydrazyl radicals and acts as a
      protector of artificially promoted linoleic acid oxidation. Under aerobic visible
      light-irradiation conditions, in the presence of Rf as the only light-absorber
      species, a complex picture of competitive processes takes place, starting with
      the quenching of singlet and triplet electronically excited states of Rf by
      ProAV. The species O2(1 g), O2(*-), H2O2, and OH(*) are generated and interact
      with ProAV. DISCUSSION: ProAV behaves as an efficient ROS scavenger. It is
      scarcely photo-oxidized by interaction with the mentioned ROS. Quantitative
      results indicate that ProAV is even more resistant to photo-oxidation than the
      recognized antioxidant trolox. Two dihydroxychalcones, mostly present in the
      ProAV composition, are responsible for the protecting activity of the propolis.

PMID- 26207875
TI  - Ventral simultanagnosia and prosopagnosia for unfamiliar faces due to a right
      posterior superior temporal sulcus and angular gyrus lesion.
AB  - We report a patient with ventral simultanagnosia, prosopagnosia for "unfamiliar
      faces" (dorsal prosopagnosia), spatial agraphia, and constructional disorder,
      particularly on the left spatial side, due to a lesion in the right posterior
      superior and middle temporal gyri and angular gyrus. The patient showed
      impairment of fundamental visual and visuospatial recognition, such as in object
      size, configuration, and horizontal point location, which probably underlay the
      mechanism of simultanagnosia and prosopagnosia. This case also suggests that the
      coexistence of simultanagnosia and prosopagnosia results from a right hemispheric
      insult, and damage to the temporoparietal area interrupts the incorporation of
      spatial information into object recognition. This disconnection of information
      flow, together with impaired object recognition per se, may impair the parallel
      processing of multiple objects, leading to object-by-object or part-by-part
      recognition. 

PMID- 26207876
TI  - Evaluation of the potential of p-nitrophenol degradation in dredged sediment by
      pulsed discharge plasma.
AB  - Hazardous pollutants in dredged sediment pose great threats to ecological
      environment and human health. A novel approach, named pulsed discharge plasma
      (PDP), was employed for the degradation of p-nitrophenol (PNP) in dredged
      sediment. Experimental results showed that 92.9% of PNP in sediment was smoothly
      removed in 60 min, and the degradation process fitted the first-order kinetic
      model. Roles of some active species in PNP degradation in sediment were studied
      by various gas plasmas, OH radical scavenger, hydrated electron scavenger and
      O2(.-) scavenger; and the results presented that O3, OH radical, eaq(-) and O2(.
      ) all played significant roles in PNP removal, and eaq(-) and O2(.-) mainly
      participated in other oxidising active species formation. FTIR analysis showed
      that PNP molecular structure was destroyed after PDP treatment. The main
      degradation intermediates were identified as hydroquinone, benzoquinone, phenol,
      acetic acid, NO2(-) and NO3(-). PNP degradation pathway in dredged sediment was
      proposed. It is expected to contribute to an alternative for sediment remediation
      by pulse discharge plasma. 

PMID- 26207877
TI  - The legacy of pesticide pollution: An overlooked factor in current risk
      assessments of freshwater systems.
AB  - We revealed a history of legacy pesticides in water and sediment samples from 19
      small streams across an agricultural landscape. Dominant legacy compounds
      included organochlorine pesticides, such as DDT and lindane, the organophosphate
      chlorpyrifos and triazine herbicides such as terbutylazine and simazine which
      have long been banned in the EU. The highest concentrations of legacy pesticides
      were found in streams draining catchments with a large proportion of arable
      farmland suggesting that they originated from past agricultural applications. The
      sum of toxic units (SumTUD.magna) based on storm water samples from
      agriculturally impacted streams was significantly higher when legacy pesticides
      were included compared to when they were omitted. Legacy pesticides did not
      significantly change the predicted toxicity of water samples to algae or fish.
      However, pesticide concentrations in bed sediment and suspended sediment samples
      exceeded safety thresholds in 50% of the samples and the average contribution of
      legacy pesticides to the SumTUC.riparius was >90%. Our results suggest that
      legacy pesticides can be highly significant contributors to the current toxic
      exposure of stream biota, especially macroinvertebrate communities, and that
      those communities were primarily exposed to legacy pesticides via the sediment.
      Additionally, our results suggest that neglecting legacy pesticides in the risk
      assessment of pesticides in streams may severely underestimate the risk of
      ecological effects. 

PMID- 26207878
TI  - Assessing the ecological long-term impact of wastewater irrigation on soil and
      water based on bioassays and chemical analyses.
AB  - The reuse of treated wastewater for irrigation and groundwater recharge can
      counteract water scarcity and reduce pollution of surface waters, but assessing
      its environmental risk should likewise consider effects associated to the soil.
      The present study therefore aimed at determining the impact of wastewater
      irrigation on the habitat quality of water after soil passage and of soil after
      percolation by applying bioassays and chemical analysis. Lab-scale columns of
      four different soils encompassing standard European soil and three field soils of
      varying characteristics and pre-contamination were continuously percolated with
      treated wastewater to simulate long-term irrigation. Wastewater and its
      percolates were tested for immobilization of Daphnia magna and growth inhibition
      of green algae (Pseudokirchneriella subcapitata) and water lentils (Lemna minor).
      The observed phytotoxicity of the treated wastewater was mostly reduced by soil
      passage, but in some percolates also increased for green algae. Chemical analysis
      covering an extensive set of wastewater-born organic pollutants demonstrated that
      many of them were considerably reduced by soil passage, particularly through
      peaty soils. Taken together, these results indicated that wastewater-born
      phytotoxic substances may be removed by soil passage, while existing soil
      pollutants (e.g. metals) may leach and impair percolate quality. Soils with and
      without wastewater irrigation were tested for growth of plants (Avena sativa,
      Brassica napus) and soil bacteria (Arthrobacter globiformis) and reproduction of
      collembolans (Folsomia candida) and oligochaetes (Enchytraeus crypticus, Eisenia
      fetida). The habitat quality of the standard and two field soils appeared to be
      deteriorated by wastewater percolation for at least one organism (enchytraeids,
      plants or bacteria), while for two pre-contaminated field soils it also was
      improved (for plants and/or enchytraeids). Wastewater percolation did not seem to
      raise soil concentrations of classical organic pollutants and priority
      substances, while a significant retention was found for zinc and several organic
      micropollutants, particularly in the peaty soils, thus matching these soils'
      observed higher removal efficiency. Overall, our results demonstrate that
      benefits of wastewater irrigation can come with the cost of deteriorating soil
      habitat quality and depend on the respective soil and considered test organism.
      The approach employed here represents a feasible tool to assess these integrated
      effects at lab-scale while being predictive for scenarios at field-scale. 

PMID- 26207879
TI  - Growth performance and oxidative damage in kidney induced by oral administration
      of Cr(III) in chicken.
AB  - This study aimed to evaluate the effects of adding chromic chloride (CrCl3) in
      the drinking water of chickens. Hyland brown male chickens were randomly divided
      into four groups. Three groups orally received 1/2 LD50, 1/4 LD50, and 1/8 LD50
      CrCl3mgkg(-1) body weight daily for 42d. The fourth group was treated with water.
      The chickens were sacrificed at 14, 28, and 42d post-treatment. The renal injury
      was examined through histological analysis, and kidney mass was determined. The
      effects on growth performance were assessed by measuring the weight of the body,
      chest muscles, and leg muscles. Oxidative damage was evaluated by determining the
      antioxidant defense levels in kidney homogenates. The body weight and the weight
      of tissues gained time-dependently, but significantly decreased compared with
      those in the control group (P<0.05) at the same exposure time. Administering
      Cr(3+) significantly increased the levels of malondialdehyde, glutathione, and
      hydrogen peroxide in the kidney compared with those in the control groups.
      Whereas, administering Cr(3+) reduced the activities of superoxide dismutase,
      catalase, glutathione peroxidase, and total an-tioxidant capacity compared with
      those in the control group (P<0.05) in a dose- and time-dependent manner. In
      conclusion, oral administration of CrCl3 decreases the growth performance of
      chickens, leads to the pathological lesions and affects nephritic antioxidant
      capacity in the kidney dose- and time-dependently.

PMID- 26207880
TI  - Medication-taking behavior in hypertensive patients with a single-tablet, fixed
      dose combination in Japan.
AB  - Non-persistence rate (defined as not remaining on treatment) in patients taking a
      renin angiotensin system inhibitor plus calcium channel blocker was studied in
      three integrated 12-weeks surveys by matching separate drug combination therapy
      (CT) and fixed-dose combination (FDC). We also investigated medication adherence
      measured by proportion of days covered by using a claims database. The non
      persistence rate was significantly lower in FDC than CT (p = 0.0074). In the
      database study, the medication adherence was higher in FDC than CT for 3, 6, and
      12 months (all p < 0.001). In conclusion, use of single-tablet FDC
      antihypertensive therapy was associated with better medication-taking behavior. 

PMID- 26207881
TI  - Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial
      degeneration in streptozotocin-induced diabetic cardiomyopathy.
AB  - Diabetic cardiomyopathy plays a major role in morbidity and mortality among
      cardiovascular disorder-related complications. This study was designed to explore
      long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin.
      Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25
      mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were
      randomly divided into 10 groups and treatments were started after 2 weeks of STZ
      administration. A gradual but severe hyperglycemia ((SSS)p < 0.001) was observed
      in all STZ-treated groups except those received insulin (2  U/day). LEVO alone
      and in combination with Ramipril and Insulin normalized (**p < 0.01) mean
      arterial pressure and heart rate, restored catalase, superoxide dismutase,
      malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised
      serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis
      factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered
      after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and
      vacuolization occurred after STZ treatment, were also reversed by LEVO in
      combination with Ramipril and Insulin. The combination of LEVO with Ramipril and
      Insulin improved hemodynamic functions, maintained cardiac enzymes and
      ameliorated myofibril damage in diabetic cardiomyopathy. 

PMID- 26207882
TI  - Association between essential hypertension and three vasoactive peptides,
      urotensin II, endothelin and adrenomedullin.
AB  - AIM: The aim of the study is to measure the vasoactive peptides, urotensin II
      (UII), endothelin (ET) and adrenomedullin (ADM) in a well-characterized
      population of normal controls and patients with essential hypertension, and to
      study their association with this disease. METHODS: The contents of plasma UII,
      ET and ADM were measured by radioimmunoassay in 40 normal controls and 120
      patients with essential hypertension. Echocardiographic examinations were
      performed using an ultrasonic system, and the left ventricular end diastolic
      diameter (LVEDd) along with the left ventricular posterior wall thickness (LVPWT)
      and interventricular septal thickness (IST) were determined. The left ventricular
      mass index (LVMI) was calculated according to the method reported by Devereux et
      al. RESULTS: Plasma UII, ET and ADM contents were increased in patients than
      healthy controls (3.28 +/- 1.257 pmol/L vs. 1.80 +/- 0.639 pmol/L, p < 0.01), and
      correlated with the severity of hypertension in patients. Besides, all the three
      vasoactive peptides in plasma had significant correlations with SBP, IST, LVPWT,
      LVMI (p <= 0.05), while they showed insignificant associations with LVEDd (p >
      0.05). UII was remarkably associated with ADM content, while the association of
      UII level with LVEDd and ET content were not significant. CONCLUSION: The
      vasoactive peptides UII, ET and ADM may be involved in the pathophysiologic
      process of essential hypertension, and function as the indicators for severity of
      this disease.

PMID- 26207883
TI  - Effect of treatment with the antioxidant alpha-lipoic (thioctic) acid on heart
      and kidney microvasculature in spontaneously hypertensive rats.
AB  - Endothelial cells represent an important vascular site of signaling and
      development of damage during ischemia, inflammation and other pathological
      conditions. Excessive reactive oxygen species production causes pathological
      activation of endothelium including exposure of cell to adhesion molecules.
      Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are members
      of the immunoglobulin super-family which are present on the surface of
      endothelial cells. These molecules represent important markers of endothelial
      inflammation. The present study was designed to investigate, with immunochemical
      and immunohistochemical techniques, the effect of treatment with (+/-)-alpha
      lipoic (thioctic) acid and its enantiomers on heart and kidney endothelium in
      spontaneously hypertensive rats (SHR). Arterial hypertension is accompanied by an
      increased oxidative stress status in the heart characterized by thiobarbituric
      acid reactive substances (TBARS) and nucleic acid oxidation increase. The higher
      oxidative stress also modifies adhesion molecules expression. In the heart VCAM
      1, which was higher than ICAM-1 and PECAM-1, was increased in SHR. ICAM-1, VCAM-1
      and PECAM-1 expression was significantly greater in the renal endothelium of SHR.
      (+/-)-Alpha lipoic acid and (+)-alpha lipoic acid treatment significantly
      decreased TBARS levels, the nucleic acid oxidation and prevented adhesion
      molecules expression in cardiac and renal vascular endothelium. These data
      suggest that endothelial molecules may be used for studying the mechanisms of
      vascular injury on target organs of hypertension. The effects observed after
      treatment with (+)-alpha lipoic acid could open new perspectives for countering
      heart and kidney microvascular injury which represent a common feature in
      hypertensive end-organs damage. 

PMID- 26207884
TI  - Targeting inflammation in metabolic syndrome.
AB  - The metabolic syndrome (MetS) is comprised of a cluster of closely related risk
      factors, including visceral adiposity, insulin resistance, hypertension, high
      triglyceride, and low high-density lipoprotein cholesterol; all of which increase
      the risk for the development of type 2 diabetes and cardiovascular disease. A
      chronic state of inflammation appears to be a central mechanism underlying the
      pathophysiology of insulin resistance and MetS. In this review, we summarize
      recent research which has provided insight into the mechanisms by which
      inflammation underlies the pathophysiology of the individual components of MetS
      including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia,
      and hypertension. On the basis of these mechanisms, we summarize therapeutic
      modalities to target inflammation in the MetS and its individual components.
      Current therapeutic modalities can modulate the individual components of MetS and
      have a direct anti-inflammatory effect. Lifestyle modifications including
      exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains,
      and low-fat dairy and low in saturated fat and glucose are recommended as a first
      line therapy. The Mediterranean and dietary approaches to stop hypertension diets
      are especially beneficial and have been shown to prevent development of MetS.
      Moreover, the Mediterranean diet has been associated with reductions in total and
      cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator
      activated receptor alpha agonists lower high levels of triglyceride; their role
      in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors,
      angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic
      therapies for hypertension but also target other aspects of MetS including
      inflammation. Statin drugs target many of the underlying inflammatory pathways
      involved in MetS.

PMID- 26207885
TI  - Helminth therapy for organic diseases?
AB  - Autoimmune and chronic inflammatory organic diseases represent a "postindustrial
      revolution epidemics," and their frequency has increased dramatically in the last
      century. Today, it is assumed that the increase in hygiene standards reduced the
      interactions with helminth parasites that coevolved with the immune system and
      are crucial for its proper functioning. Several helminths have been proposed and
      tested in the search of the ideal therapeutic. In this review, the authors
      summarize the translational and clinical studies and review the caveats and
      possible solutions for the optimization of helminth therapies. 

PMID- 26207886
TI  - Interferon regulatory factor 5 in human autoimmunity and murine models of
      autoimmune disease.
AB  - Interferon regulatory factor 5 (IRF5) has been demonstrated as a key
      transcription factor of the immune system, playing important roles in modulating
      inflammatory immune responses in numerous cell types including dendritic cells,
      macrophages, and B cells. As well as driving the expression of type I interferon
      in antiviral responses, IRF5 is also crucial for driving macrophages toward a
      proinflammatory phenotype by regulating cytokine and chemokine expression and
      modulating B-cell maturity and antibody production. This review highlights the
      functional importance of IRF5 in a disease setting, by discussing polymorphic
      mutations at the human Irf5 locus that lead to susceptibility to systemic lupus
      erythematosus, rheumatoid arthritis, and inflammatory bowel disease. In
      concordance with this, we also discuss lessons in IRF5 functionality learned from
      murine in vivo models of autoimmune disease and inflammation and hypothesize that
      modulation of IRF5 activity and expression could provide potential therapeutic
      benefits in the clinic.

PMID- 26207887
TI  - Antioxidant enzyme systems and the ascorbate-glutathione cycle as contributing
      factors to cadmium accumulation and tolerance in two oilseed rape cultivars
      (Brassica napus L.) under moderate cadmium stress.
AB  - Oilseed rape (Brassica napus L.) with high tolerance to cadmium (Cd) may be used
      in the phytoremediation of Cd-contaminated fields. However, the mechanisms
      responsible for Cd accumulation and tolerance in oilseed rape are still poorly
      understood. Here, we investigated the physiological and molecular processes
      involved in Cd tolerance of two oilseed rape cultivars with different Cd
      accumulation abilities. The total Cd accumulation in cultivar L351 was higher
      than cultivar L338, particularly with increasing concentrations of Cd exposure.
      L338 was a more pronounced Cd-sensitive cultivar than L351, while higher
      activities of antioxidant enzymes (CAT, APX, GR, DHAR) as well as higher contents
      of GSH and AsA were all observed in L351 under Cd treatments, especially at high
      levels. No differences were found in SOD activities between the two cultivars
      under the same Cd treatments, suggesting that SOD was not the key factor in
      relation to the differences of Cd tolerance and accumulation between them. Gene
      expression levels of BnFe-SOD, BnCAT, BnAPX, BcGR and BoDHAR in roots of L351
      were relatively higher than that in L338 under Cd exposure as well as BnCAT and
      BcGR in leaves. It is concluded that antioxidant enzymes and the ascorbate
      glutathione cycle play important roles in oilseed rape Cd accumulation and
      tolerance. 

PMID- 26207888
TI  - A historical overview of protein kinases and their targeted small molecule
      inhibitors.
AB  - Protein kinases play a predominant regulatory role in nearly every aspect of cell
      biology and they can modify the function of a protein in almost every conceivable
      way. Protein phosphorylation can increase or decrease enzyme activity and it can
      alter other biological activities such as transcription and translation.
      Moreover, some phosphorylation sites on a given protein are stimulatory while
      others are inhibitory. The human protein kinase gene family consists of 518
      members along with 106 pseudogenes. Furthermore, about 50 of the 518 gene
      products lack important catalytic residues and are called protein pseudokinases.
      The non-catalytic allosteric interaction of protein kinases and pseudokinases
      with other proteins has added an important regulatory feature to the biochemistry
      and cell biology of the protein kinase superfamily. With rare exceptions, a
      divalent cation such as Mg2+ is required for the reaction. All protein kinases
      exist in a basal state and are activated only as necessary by divergent
      regulatory stimuli. The mechanisms for switching between dormant and active
      protein kinases can be intricate. Phosphorylase kinase was the first protein
      kinase to be characterized biochemically and the mechanism of its regulation led
      to the discovery of cAMP-dependent protein kinase (protein kinase A, or PKA),
      which catalyzes the phosphorylation and activation of phosphorylase kinase. This
      was the first protein kinase cascade or signaling module to be elucidated. The
      epidermal growth factor receptor-Ras-Raf-MEK-ERK signaling module contains
      protein-tyrosine, protein-serine/threonine, and dual specificity protein kinases.
      PKA has served as a prototype of this enzyme family and more is known about this
      enzyme than any other protein kinase. The inactive PKA holoenzyme consists of two
      regulatory and two catalytic subunits. After binding four molecules of cAMP, the
      holoenzyme dissociates into a regulatory subunit dimer (each monomer binds two
      cAMP) and two free and active catalytic subunits. PKA and all other protein
      kinase domains have a small amino-terminal lobe and large carboxyterminal lobe as
      determined by X-ray crystallography. The N-lobe and C-lobe form a cleft that
      serves as a docking site for MgATP. Nearly all active protein kinases contain a
      K/E/D/D signature sequence that plays important structural and catalytic roles.
      Protein kinases contain hydrophobic catalytic and regulatory spines and
      collateral shell residues that are required to assemble the active enzyme. There
      are two general kinds of conformational changes associated with most protein
      kinases. The first conformational change involves the formation of an intact
      regulatory spine to form an active enzyme. The second conformational change
      occurs in active kinases as they toggle between open and closed conformations
      during their catalytic cycles. Because mutations and dysregulation of protein
      kinases play causal roles in human disease, this family of enzymes has become one
      of the most important drug targets over the past two decades. Imatinib was
      approved by the United States FDA for the treatment of chronic myelogenous
      leukemia in 2001; this small molecule inhibits the BCR-Abl protein kinase
      oncoprotein that results from the formation of the Philadelphia chromosome. More
      than two dozen other orally effective mechanism-based small molecule protein
      kinase inhibitors have been subsequently approved by the FDA. These drugs bind to
      the ATP-binding site of their target enzymes and extend into nearby hydrophobic
      pockets. Most of these protein kinase inhibitors prolong survival in cancer
      patients only weeks or months longer than standard cytotoxic therapies. In
      contrast, the clinical effectiveness of imatinib against chronic myelogenous
      leukemia is vastly superior to that of any other targeted protein kinase
      inhibitor with overall survival lasting a decade or more. However, the near
      universal and expected development of drug resistance in the treatment of
      neoplastic disorders requires new approaches to solve this therapeutic challenge.
      Cancer is the predominant indication for these drugs, but disease targets are
      increasing. For example, we can expect the approval of new drugs inhibiting other
      protein kinases in the treatment of illnesses such as hypertension, Parkinson's
      disease, and autoimmune diseases.

PMID- 26207890
TI  - Dangers associated with civil nuclear power programmes: weaponization and nuclear
      waste.
AB  - The number of nuclear power plants in the world rose exponentially to 420 by 1990
      and peaked at 438 in 2002; but by 2014, as closed plants were not replaced, there
      were just 388. In spite of using more renewable energy, the world still relies on
      fossil fuels, but some countries plan to develop new nuclear programmes. Spent
      nuclear fuel, one of the most dangerous and toxic materials known, can be
      reprocessed into fresh fuel or into weapons-grade materials, and generates large
      amounts of highly active waste. This article reviews available literature on
      government and industry websites and from independent analysts on world energy
      production, the aspirations of the 'new nuclear build' programmes in China and
      the UK, and the difficulties in keeping the environment safe over an immense
      timescale while minimizing adverse health impacts and production of greenhouse
      gases, and preventing weaponization by non-nuclear-weapons states acquiring civil
      nuclear technology.

PMID- 26207889
TI  - Curcumin Inhibits Neuronal Loss in the Retina and Elevates Ca2+/Calmodulin
      Dependent Protein Kinase II Activity in Diabetic Rats.
AB  - PURPOSE: To determine whether curcumin offers neuroprotection to minimize the
      apoptosis of neural cells in the retina of diabetic rats. METHODS: Streptozotocin
      (STZ)-induced diabetic rats and control rats were used in this study. A subgroup
      of STZ-induced diabetic rats were treated with curcumin for 12 weeks. Retinal
      histology, apoptosis of neural cells in the retina, electroretinograms, and
      retinal glutamate content were evaluated after 12 weeks. Retinal levels of
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), phospho-CaMKII (p
      CaMKII), and cleaved caspase-3 were determined by Western blot analysis. RESULTS:
      The amplitudes a-wave, b-wave, and oscillatory potential were reduced by
      diabetes, but curcumin treatment suppressed this reduction of amplitudes.
      Curcumin also prevented cell loss from the outer nuclear, inner nuclear, and
      ganglion cell layers. Apoptosis of retinal neurons was detected in diabetic rats.
      The concentration of glutamate in the retina was higher in diabetic rats, but was
      significantly reduced in the curcumin-treated group. Furthermore, p-CaMKII and
      cleaved caspase-3 expression were upregulated in the diabetic retina, but reduced
      in curcumin-treated rats. CONCLUSIONS: Curcumin attenuated diabetes-induced
      apoptosis in retinal neurons by reducing the glutamate level and downregulating
      CaMKII. Thus, curcumin might be used to prevent neuronal damage in the retina of
      patients with diabetes mellitus.

PMID- 26207891
TI  - Probing the Molecular Origin of Native-State Flexibility in Repeat Proteins.
AB  - In contrast to globular proteins, the structure of repeat proteins is dominated
      by a regular set of short-range interactions. This property may confer on the
      native state of such proteins significant elasticity. We probe the molecular
      origin of the spring-like behavior of repeat proteins using a designed
      tetratricopeptide repeat protein with three repeat units (CTPR3). Single-molecule
      fluorescence studies of variants of the protein with FRET pairs at different
      positions show a continuous expansion of the folded state of CTPR3 at low
      concentrations of a chemical denaturant, preceding the all-or-none transition to
      the unfolded state. This remarkable native-state expansion can be explained
      quantitatively by a reduction in the spring constant of the structure. Circular
      dichroism and tryptophan fluorescence spectroscopy further show that the
      expansion does not involve either unwinding of CTPR3 helices or unraveling of
      interactions within repeats. These findings point to hydrophobic inter-repeat
      contacts as the source of the elasticity of repeat proteins. 

PMID- 26207892
TI  - Eltoprazine prevents levodopa-induced dyskinesias by reducing striatal glutamate
      and direct pathway activity.
AB  - BACKGROUND: Preclinical and clinical evidence that the serotonergic system plays
      a major role in levodopa-induced dyskinesias has been provided. Selective
      serotonin (5-hydroxytryptamine; 5-HT) 5-HT1A or 5-HT1B receptor agonists, and,
      very recently, the mixed 5-HT1A /5-HT1B receptor agonist, eltoprazine, proved
      effective in inhibiting L-dopa-induced dyskinesias in experimental animals and
      parkinsonian patients. Here, we investigate the mechanisms underlying this
      effect. METHODS: Microdialysis was employed in 6-hydroxydopamine-hemilesioned
      rats chronically treated with L-dopa alone or in combination with eltoprazine.
      Gamma-aminobutyric acid (GABA) and glutamate levels were monitored on L-dopa in
      the dopamine-depleted striatum and ipsilateral SNr. Motor activity on the rotarod
      was assessed, both off and on L-dopa. Western blot was used to quantify ex vivo
      striatal levels of phosphorylated extracellular signal-regulated kinase 1 and 2.
      Striatal and nigral amino acid levels, as well as striatal dopamine levels, were
      also monitored in L-dopa-primed dyskinetic rats acutely challenged with L-dopa
      and eltoprazine. RESULTS: Eltoprazine attenuated the development and expression
      of dyskinesias, preserving motor coordination on the rotarod. Eltoprazine
      prevented the rise of nigral amino acids and striatal glutamate levels, as well
      as the increase in striatal phosphorylated extracellular signal-regulated kinase
      1 and 2, associated with dyskinesias. However, eltoprazine did not affect the L
      dopa-induced increase in striatal dopamine. CONCLUSIONS: Eltoprazine inhibits the
      sensitization of striatonigral medium-sized GABA spiny neurons (the direct
      pathway) to L-dopa and their overactivation associated with dyskinesias
      appearance. Activation of 5-HT1A and 5-HT1B receptors regulating striatal
      glutamate transmission, but not striatal ectopic dopamine release, might underlie
      the symptomatic effect of eltoprazine.

PMID- 26207893
TI  - A Biophysical Model for the Staircase Geometry of Stereocilia.
AB  - Cochlear hair cell bundles, made up of 10s to 100s of individual stereocilia, are
      essential for hearing, and even relatively minor structural changes, due to
      mutations or injuries, can result in total deafness. Consistent with its
      specialized role, the staircase geometry (SCG) of hair cell bundles presents one
      of the most striking, intricate, and precise organizations of actin-based
      cellular shapes. Composed of rows of actin-filled stereocilia with increasing
      lengths, the hair cell's staircase-shaped bundle is formed from a progenitor
      field of smaller, thinner, and uniformly spaced microvilli with relatively
      invariant lengths. While recent genetic studies have provided a significant
      increase in information on the multitude of stereocilia protein components, there
      is currently no model that integrates the basic physical forces and biochemical
      processes necessary to explain the emergence of the SCG. We propose such a model
      derived from the biophysical and biochemical characteristics of actin-based
      protrusions. We demonstrate that polarization of the cell's apical surface, due
      to the lateral polarization of the entire epithelial layer, plays a key role in
      promoting SCG formation. Furthermore, our model explains many distinct features
      of the manifestations of SCG in different species and in the presence of various
      deafness-associated mutations. 

PMID- 26207894
TI  - Effect of climate change, CO2 trends, nitrogen addition, and land-cover and
      management intensity changes on the carbon balance of European grasslands.
AB  - Several lines of evidence point to European managed grassland ecosystems being a
      sink of carbon. In this study, we apply ORCHIDEE-GM a process-based carbon cycle
      model that describes specific management practices of pastures and the dynamics
      of carbon cycling in response to changes in climatic and biogeochemical drivers.
      The model is used to simulate changes in the carbon balance [i.e., net biome
      production (NBP)] of European grasslands over 1991-2010 on a 25 km * 25 km grid.
      The modeled average trend in NBP is 1.8-2.0 g C m(-2)  yr(-2) during the past two
      decades. Attribution of this trend suggests management intensity as the dominant
      driver explaining NBP trends in the model (36-43% of the trend due to all
      drivers). A major change in grassland management intensity has occurred across
      Europe resulting from reduced livestock numbers. This change has 'inadvertently'
      enhanced soil C sequestration and reduced N2 O and CH4 emissions by 1.2-1.5 Gt
      CO2 -equivalent, offsetting more than 7% of greenhouse gas emissions in the whole
      European agricultural sector during the period 1991-2010. Land-cover change,
      climate change and rising CO2 also make positive and moderate contributions to
      the NBP trend (between 24% and 31% of the trend due to all drivers). Changes in
      nitrogen addition (including fertilization and atmospheric deposition) are found
      to have only marginal net effect on NBP trends. However, this may not reflect
      reality because our model has only a very simple parameterization of nitrogen
      effects on photosynthesis. The sum of NBP trends from each driver is larger than
      the trend obtained when all drivers are varied together, leaving a residual -
      nonattributed - term (22-26% of the trend due to all drivers) indicating negative
      interactions between drivers. 

PMID- 26207895
TI  - HPV Infection and Cervical Screening in Socially Isolated Indigenous Women
      Inhabitants of the Amazonian Rainforest.
AB  - OBJECTIVE: Indigenous women from the Amazon regions have some of the highest
      rates of cervical cancer in the world. This study evaluated cervical cytology and
      human papillomavirus (HPV) in native women that differ by lifestyle and
      interaction with western society. Yanomami women are isolated deep in the Amazon
      with a hunter/gatherer lifestyle. Macuxi and Wapishana women live in proximity to
      western society. METHODS: To select a representative group of women from each
      district, random cluster sampling was used, considering each registered village
      as a cluster. Cervical samples were collected for cytology and HPV detection and
      typing by PCR amplification and next generation sequencing. The study was
      approved by the National IRB and by tribal leaders. RESULTS: 664 native women
      were enrolled from 13 indigenous villages (76% participation rate). Yanomami
      women had higher rates of abnormal cytology (5.1% vs. 1.8%, p = 0.04) and
      prevalent HR-HPV (34.1% vs. 19.2%, p<0.001). Yanomami women >35 y of age were
      significantly more likely to have HR-HPV, whereas women <= 35 y did not
      significantly differ between groups. Prevalence of HPV was significantly
      different amongst geographically clustered Yanomami women (p<0.004). The most
      prevalent HPV types in the entire group were HPV31 (8.7%), HPV16 (5.9%) and HPV18
      (4.4%). CONCLUSION: Isolated endogenous Yanomami women were more likely to be
      HPV+ and rates increased with age. Study of HPV in isolated hunter-gather peoples
      suggests that long-term persistence is a characteristic of prehistoric humans and
      patterns reflecting decreased prevalence with age in western society represents
      recent change. These studies have implications for cervical cancer prevention and
      viral-host relationships.

PMID- 26207896
TI  - Characterization by Small RNA Sequencing of Taro Bacilliform CH Virus (TaBCHV), a
      Novel Badnavirus.
AB  - RNA silencing is an antiviral immunity that regulates gene expression through the
      production of small RNAs (sRNAs). In this study, deep sequencing of small RNAs
      was used to identify viruses infecting two taro plants. Blast searching
      identified five and nine contigs assembled from small RNAs of samples T1 and T2
      matched onto the genome sequences of badnaviruses in the family Caulimoviridae.
      Complete genome sequences of two isolates of the badnavirus determined by
      sequence specific amplification comprised of 7,641 nucleotides and shared overall
      nucleotide similarities of 44.1%-55.8% with other badnaviruses. Six open reading
      frames (ORFs) were identified on the plus strand, showed amino acid similarities
      ranging from 59.8% (ORF3) to 10.2% (ORF6) to the corresponding proteins encoded
      by other badnaviruses. Phylogenetic analysis also supports that the virus is a
      new member in the genus Badnavirus. The virus is tentatively named as Taro
      bacilliform CH virus (TaBCHV), and it is the second badnavirus infecting taro
      plants, following Taro bacilliform virus (TaBV). In addition, analyzes of viral
      derived small RNAs (vsRNAs) from TaBCHV showed that almost equivalent number of
      vsRNAs were generated from both strands and the most abundant vsRNAs were 21 nt,
      with uracil bias at 5' terminal. Furthermore, TaBCHV vsRNAs were asymmetrically
      distributed on its entire circular genome at both orientations with the hotspots
      mainly generated in the ORF5 region. 

PMID- 26207897
TI  - Structural Plasticity of Dendritic Spines Requires GSK3alpha and GSK3beta.
AB  - Although memories appear to be elusive phenomena, they are stored in the network
      of physical connections between neurons. Dendritic spines, which are actin-rich
      dendritic protrusions, serve as the contact points between networked neurons. The
      spines' shape contributes to the strength of signal transmission. To acquire and
      store information, dendritic spines must remain plastic, i.e., able to respond to
      signals, by changing their shape. We asked whether glycogen synthase kinase (GSK)
      3alpha and GSK3beta, which are implicated in diseases with neuropsychiatric
      symptoms, such as Alzheimer's disease, bipolar disease and schizophrenia, play a
      role in a spine structural plasticity. We used Latrunculin B, an actin
      polymerization inhibitor, and chemically induced Long-Term Depression to trigger
      fast spine shape remodeling in cultured hippocampal neurons. Spine shrinkage
      induced by either stimulus required GSK3alpha activity. GSK3beta activity was
      only important for spine structural changes after treatment with Latrunculin B.
      Our results indicate that GSK3alpha is an essential component for short-term
      spine structural plasticity. This specific function should be considered in
      future studies of neurodegenerative diseases and neuropsychiatric conditions that
      originate from suboptimal levels of GSK3alpha/beta activity.

PMID- 26207898
TI  - Serum Levels of Human MIC-1/GDF15 Vary in a Diurnal Pattern, Do Not Display a
      Profile Suggestive of a Satiety Factor and Are Related to BMI.
AB  - The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy
      humans. Its levels rise substantially in cancer and other diseases and this may
      sometimes lead to development of an anorexia/cachexia syndrome. This is mediated
      by a direct action of MIC-1/GDF15 on feeding centres in the hypothalamus and
      brainstem. More recent studies in germline gene deleted mice also suggest that
      this cytokine may play a role in physiological regulation of energy homeostasis.
      To further characterize the role of MIC-1/GDF15 in physiological regulation of
      energy homeostasis in man, we have examined diurnal and food associated variation
      in serum levels and whether variation in circulating levels relate to BMI in
      human monozygotic twin pairs. We found that the within twin pair differences in
      serum MIC-1/GDF15 levels were significantly correlated with within twin pair
      differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy
      balance in man. MIC-1/GDF15 serum levels altered slightly in response to a meal,
      but comparison with variation its serum levels over a 24 hour period suggested
      that these changes are likely to be due to bimodal diurnal variation which can
      alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The
      lack of a rapid and substantial postprandial increase in MIC-1/GDF15 serum levels
      suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together,
      our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy
      homeostasis in man, most probably due to actions on long-term regulation of
      energy homeostasis.

PMID- 26207899
TI  - Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti
      Tumorigenic and Anti-Angiogenic Activity.
AB  - Numerous studies have shown a paradoxical positive correlation between elevated
      levels of plasminogen activator inhibitior-1 (PAI-1) in tumors and blood of
      cancer patients with poor clinical outcome, suggesting that PAI-1 could be a
      therapeutic target. Here we tested two orally bioavailable small molecule
      inhibitors of PAI-1 (TM5275 and TM5441) for their efficacy in pre-clinical models
      of cancer. We demonstrated that these inhibitors decreased cell viability in
      several human cancer cell lines with an IC50 in the 9.7 to 60.3 MUM range and
      induced intrinsic apoptosis at concentrations of 50 MUM. In vivo, oral
      administration of TM5441 (20 mg/kg daily) to HT1080 and HCT116 xenotransplanted
      mice increased tumor cell apoptosis and had a significant disruptive effect on
      the tumor vasculature that was associated with a decrease in tumor growth and an
      increase in survival that, however, were not statistically significant.
      Pharmacokinetics studies indicated an average peak plasma concentration of 11.4
      MUM one hour after oral administration and undetectable levels 23 hours after
      administration. The effect on tumor vasculature in vivo was further examined in
      endothelial cells (EC) in vitro and this analysis indicated that both TM5275 and
      TM5441 inhibited EC branching in a 3D Matrigel assay at concentrations where they
      had little effect on EC apoptosis. These studies bring novel insight on the
      activity of PAI-1 inhibitors and provide important information for the future
      design of inhibitors targeting PAI-1 as therapeutic agents in cancer. 

PMID- 26207900
TI  - Self-Compassion, Emotion Regulation and Stress among Australian Psychologists:
      Testing an Emotion Regulation Model of Self-Compassion Using Structural Equation
      Modeling.
AB  - Psychologists tend to report high levels of occupational stress, with serious
      implications for themselves, their clients, and the discipline as a whole. Recent
      research suggests that self-compassion is a promising construct for psychologists
      in terms of its ability to promote psychological wellbeing and resilience to
      stress; however, the potential benefits of self-compassion are yet to be
      thoroughly explored amongst this occupational group. Additionally, while a
      growing body of research supports self-compassion as a key predictor of
      psychopathology, understanding of the processes by which self-compassion exerts
      effects on mental health outcomes is limited. Structural equation modelling (SEM)
      was used to test an emotion regulation model of self-compassion and stress among
      psychologists, including postgraduate trainees undertaking clinical work (n =
      198). Self-compassion significantly negatively predicted emotion regulation
      difficulties and stress symptoms. Support was also found for our preliminary
      explanatory model of self-compassion, which demonstrates the mediating role of
      emotion regulation difficulties in the self-compassion-stress relationship. The
      final self-compassion model accounted for 26.2% of variance in stress symptoms.
      Implications of the findings and limitations of the study are discussed. 

PMID- 26207901
TI  - Theoretical Study on the Solvation of C60 Fullerene by Ionic Liquids II: DFT
      Analysis of the Interaction Mechanism.
AB  - As a continuation of our previous work (J. Phys. Chem. B, 2014, 118, 11330) on
      the solvation of C60 by ionic liquids (ILs) using Molecular Dynamic simulations,
      this paper reports a systematic density functional theory (DFT) analysis on the
      interaction mechanism between C60 and 24 different ionic liquids (belonging to
      the imidazolium, piperazinium, and cholinium groups). Properties such as binding
      energies, charge distributions, intermolecular interactions, or electronic
      structure were analyzed as a function of the selected ILs. The stronger IL-C60
      interactions would be related with pi-pi stacking between the C60 surface and
      anions such as salycilate ([SA]). Likewise, the electronic structure analysis
      pointed to a well-defined relationship between the energetics of IL-C60 systems
      and IL features. Therefore, ILs with deep HOMO energies as well as weak
      interaction between both ions would be a priori good candidates for C60
      solvation. Although only short-range interactions are studied in the framework of
      DFT, this work provides useful information for the rational design of ILs that
      could exhibit suitable features as C60 solvents. 

PMID- 26207902
TI  - Impact of TG4010 Vaccine on Health-Related Quality of Life in Advanced Non-Small
      Cell Lung Cancer: Results of a Phase IIB Clinical Trial.
AB  - BACKGROUND: This study describes the effect of TG4010 vaccine on Health related
      Quality of Life (HRQOL) in patients with stage IIIb and IV non-small-cell lung
      cancer (NSCLC). METHODS: 148 patients with advanced NSCLC expressing MUC1 were
      randomly assigned to receive TG4010 plus chemotherapy or chemotherapy alone.
      HRQOL was assessed with the Functional Assessment of Cancer Therapy-Lung (FACT-L)
      at baseline and every 6 weeks until disease progression. Time until definitive
      deterioration (TUDD) of the four well-being dimensions of the FACT-L physical
      (PWB), functional (FWB), emotional (EWB) and social well-being (SWB) and the Lung
      Cancer Subscale (LCS) domains were analyzed for a 5-point minimal clinically
      important difference. RESULTS: No difference of TUDD of HRQOL has been found
      between treatment arms. No prognostic factors have been found to have a
      significant impact on the TUDD of PWB, SWB and LCS domains. The gender, the
      performance status and the smoking habits seemed to be associated with a shorter
      TUDD of EWB domain. The smokers and the former smokers seemed to present a
      shorter TUDD of FWB domain. CONCLUSION: This study suggests that adding
      therapeutic vaccination with TG4010 to standard chemotherapy in patients with
      advanced NSCLC is associated with a similar evolution in HRQOL compared to
      chemotherapy alone.

PMID- 26207903
TI  - The Hidden Diversity of Zanclea Associated with Scleractinians Revealed by
      Molecular Data.
AB  - Scleractinian reef corals have recently been acknowledged as the most numerous
      host group found in association with hydroids belonging to the Zanclea genus.
      However, knowledge of the molecular phylogenetic relationships among Zanclea
      species associated with scleractinians is just beginning. This study, using the
      nuclear 28S rDNA region and the fast-evolving mitochondrial 16S rRNA and COI
      genes, provides the most comprehensive phylogenetic reconstruction of the genus
      Zanclea with a particular focus on the genetic diversity among Zanclea specimens
      associated with 13 scleractinian genera. The monophyly of Zanclea associated with
      scleractinians was strongly supported in all nuclear and mitochondrial
      phylogenetic reconstructions. Furthermore, a combined mitochondrial 16S and COI
      phylogenetic tree revealed a multitude of hidden molecular lineages within this
      group (Clades I, II, III, V, VI, VII, and VIII), suggesting the existence of both
      host-generalist and genus-specific lineages of Zanclea associated with
      scleractinians. In addition to Z. gallii living in association with the genus
      Acropora, we discovered four well-supported lineages (Clades I, II, III, and
      VII), each one forming a strict association with a single scleractinian genus,
      including sequences of Zanclea associated with Montipora from two geographically
      separated areas (Maldives and Taiwan). Two host-generalist Zanclea lineages were
      also observed, and one of them was formed by Zanclea specimens symbiotic with
      seven scleractinian genera (Clade VIII). We also found that the COI gene allows
      the recognition of separated hidden lineages in agreement with the commonly
      recommended mitochondrial 16S as a DNA barcoding gene for Hydrozoa and shows
      reasonable potential for phylogenetic and evolutionary analyses in the genus
      Zanclea. Finally, as no DNA sequences are available for the majority of the
      nominal Zanclea species known, we note that they will be necessary to elucidate
      the diversity of the Zanclea-scleractinian association. 

PMID- 26207904
TI  - Exploring the phenomenon of spiritual care between hospital chaplains and
      hospital based healthcare providers.
AB  - Hospital chaplaincy and spiritual care services are important to patients'
      medical care and well-being; however, little is known about healthcare providers'
      experiences receiving spiritual support. A phenomenological study examined the
      shared experience of spiritual care between hospital chaplains and hospital-based
      healthcare providers (HBHPs). Six distinct themes emerged from the in-depth
      interviews: Awareness of chaplain availability, chaplains focus on building
      relationships with providers and staff, chaplains are integrated in varying
      degrees on certain hospital units, chaplains meet providers' personal and
      professional needs, providers appreciate chaplains, and barriers to expanding
      hospital chaplains' services. While HBHPs appreciated the care received and were
      able to provide better patient care as a result, participants reported that
      administrators may not recognize the true value of the care provided.
      Implications from this study are applied to hospital chaplaincy clinical,
      research, and training opportunities. 

PMID- 26207905
TI  - The Affordable Care Act and hospital chaplaincy: re-visioning spiritual care, re
      valuing institutional wholeness.
AB  - This article focuses on the institutional dimensions of spiritual care within
      hospital settings in the context of the Patient Protection and Affordable Care
      Act of 2010 (ACA), applying policy information and systems theory to re-imagine
      the value and function of chaplaincy to hospital communities. This article argues
      that chaplaincy research and practice must look beyond only individual
      interventions and embrace chaplain competencies of presence, ritual, and
      communication as foundational tools for institutional spiritual care. 

PMID- 26207906
TI  - Measures of variability in chaplaincy, health care, and related research.
AB  - This article discusses statistical measures of variability in relation to
      measures of central tendency and levels of measurement. Three measures of
      variability used in healthcare research (the range, the interquartile range, and
      the standard deviation) are described and compared, including their uses and
      limitations. The article describes how each of the three measures is calculated,
      and it provides a step-by-step example of calculating the sums of squares,
      variance, and standard deviation. Graphs of frequency and percentage
      distributions are used to show how the interquartile range and the standard
      deviation represent the variability observed within distributions. The article
      discusses the properties of the normal curve regarding the distribution of scores
      around the mean in relation to the standard deviation, and illustrates
      differences in the shapes of normal curves with the same mean but different
      standard deviations. 

PMID- 26207908
TI  - Do Small Canopy Gaps Created by Japanese Black Bears Facilitate Fruiting of
      Fleshy-Fruited Plants?
AB  - Japanese black bears often break branches when climbing trees and feeding on
      fruit in canopies, thereby creating small canopy gaps. However, the role of black
      bear-created canopy gaps has not been evaluated in the context of multiple forest
      dynamics. Our hypothesis was that small canopy gaps created by black bears
      improve light conditions, which facilitates fruiting of adult fleshy-fruited
      plants located beneath the gaps, and also that this chain interaction depends on
      interactions among the size of gaps, improved light conditions, forest layers,
      and life form of plants. The rPPFD, size of black bear-created canopy gaps, and
      fruiting/non-fruiting of fleshy-fruited plants were investigated in five forest
      layers beneath black-bear-created canopy gaps and closed canopies of Mongolian
      oak (Quercus crispula). We found that light conditions improved beneath black
      bear-disturbed trees with canopy gaps of large size, and the effect of
      improvement of light conditions was reduced with descending forest layers.
      Fruiting of fleshy-fruited plants, especially woody lianas and trees, was
      facilitated by the improvement of light conditions accompanied by an increase in
      the size of black-bear-created gaps. Data from this study revealed that canopy
      disturbance by black bears was key for improving light conditions and
      accelerating fruiting of fleshy-fruited trees and woody lianas in the canopy
      layers in particular. Therefore, our hypothesis was mostly supported. Our results
      provide evidence that Japanese black bears have high potential as ecosystem
      engineers that increase the availability of resources (light and fruit in this
      study) to other species by causing physical state changes in biotic materials
      (branches of Q. crispula in this study). 

PMID- 26207907
TI  - Simvastatin Increases Fibulin-2 Expression in Human Coronary Artery Smooth Muscle
      Cells via RhoA/Rho-Kinase Signaling Pathway Inhibition.
AB  - The composition and structure of the extracellular matrix (ECM) in the vascular
      wall and in the atherosclerotic plaque are important factors that determine
      plaque stability. Statins can stabilize atherosclerotic plaques by modulating ECM
      protein expression. Fibulins are important components of the ECM. We evaluated
      the in vitro effect of simvastatin on the expression of fibulin-1, -2, -4 and -5
      in human coronary artery smooth muscle cells (SMCs) and the mechanisms involved.
      Cells were incubated with simvastatin (0.05-1 MUM), mevalonate (100 and 200 MUM),
      geranylgeranyl pyrophosphate (GGPP) (15 MUM), farnesyl pyrophosphate (FPP) (15
      MUM), the Rho kinase (ROCK) inhibitor Y-27632 (15 and 20 MUM), the Rac-1
      inhibitor (another member of Rho family) NSC23766 (100 MUM), arachidonic acid (a
      RhoA/ROCK activator, 25-100 MUM) and other fatty acids that are not activators of
      RhoA/ROCK (25-100 MUM). Gene expression was analyzed by quantitative real-time
      PCR, and fibulin protein levels were analyzed by western blotting and ELISA.
      Simvastatin induced a significant increase in mRNA and protein levels of fibulin
      2 at 24 hours of incubation (p<0.05), but it did not affect fibulin-1, -4, and -5
      expression. Mevalonate and GGPP were able to reverse simvastatin's effect, while
      FPP did not. In addition, Y-27632, but not NSC23766, significantly increased
      fibulin-2 expression. Furthermore, activation of the RhoA/ROCK pathway with
      arachidonic acid decreased fibulin-2 mRNA. Simvastatin increased mRNA levels and
      protein expression of the ECM protein fibulin-2 through a RhoA and Rho-Kinase
      mediated pathway. This increase could affect the composition and structure of the
      ECM. 

PMID- 26207909
TI  - Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters
      for Different Molecular Subtypes of Breast Cancer.
AB  - BACKGROUND & AIMS: The utility of measuring carcinoembryonic antigen(CEA) and
      cancer antigen 15-3 (CA15-3) levels in patients with breast cancer remains
      controversial. The present study aims to investigate the prognostic value of
      preoperative serum CEA and CA15-3 levels in breast cancer patients. METHODS:
      Serum preoperative CEA and CA 15-3 concentration levels were measured in a total
      of 432 breast cancer patients. The association of tumor markers levels with
      clinicopathological parameters and outcomes were analyzed. RESULTS: Elevated
      serum levels of CEA and CA15-3 were identified in 47 (10.9%) and 60(13.9%)
      patients, respectively. Larger tumor size, advanced axillary lymph nodal and TNM
      stage exhibited higher proportion of elevated CEA and CA15-3 levels. The
      elevation of CEA levels was significantly greater in patients with HER2 positive
      tumors, and the elevation of CA15-3 levels was significantly greater in ER
      negative breast patients. Univariate and multivariate Cox's regression analysis
      revealed that elevated preoperative CEA and CA 15-3 levels were independent
      prognostic factors for DFS and OS. When considering the combination of both
      markers levels, patients with both elevated markers presented the worst survival.
      Independent prognostic significance of elevated preoperative serum CEA and CA15-3
      levels were reconfirmed in Luminal B breast cancer. CONCLUSIONS: Preoperative
      serum levels of CEA and CA15-3 are independent prognostic parameters for breast
      cancer.

PMID- 26207910
TI  - The garlic compound ajoene targets protein folding in the endoplasmic reticulum
      of cancer cells.
AB  - Ajoene is a natural allylsulfur compound found in crushed garlic that arrests
      growth and induces apoptosis in cancer cells. To gain mechanistic insights into
      the cytotoxicity of ajoene in cancer cells, two fluorescently labelled ajoene
      analogs with dansyl- (DP) and fluorescein- (FOX) tags were synthesized. The
      tagged ajoenes were found to retain their activity at inhibiting proliferation
      and inducing apoptosis in MDA-MB-231 human breast-cancer and WHCO1 human
      esophageal-cancer cells. Both tagged ajoenes localized to the endoplasmic
      reticulum (ER) in MDA-MB-231 cells as observed by live cell confocal laser
      scanning microscopy (CLSM) and confirmed by generating an MDA-MB-231 cell line
      expressing yellow fluorescent protein (YFP) in the ER. DP appears to S-thiolate
      multiple protein targets in MDA-MB-231 cells as observed by immunoblotting under
      non-reducing conditions only; and a competition assay demonstrated that DP and Z
      ajoene in fact share the same target. Ajoene S-thiolation interfered with protein
      folding and led to an accumulation of misfolded protein aggregates and activated
      the unfolded protein response (UPR). Consistent with this mechanism, increased
      levels of GRP78 and total ubiquitinated proteins were observed; and an ER-folded
      protein, type-1 collagen, was tracked to the proteasome following ajoene
      treatment. The intracellular protein aggregates were observed by CLSM and
      transmission electron microscopy (TEM). This is the first time that ajoene has
      been shown to target protein folding in the ER of cancer cells. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26207911
TI  - Zic1 Promoter Hypermethylation in Plasma DNA Is a Potential Biomarker for Gastric
      Cancer and Intraepithelial Neoplasia.
AB  - Gastric cancer (GC) remains one of the most common digestive cancers worldwide;
      however, most patients present at an advanced stage at initial diagnosis. Zic1 is
      a novel candidate tumor suppressor gene that is epigenetically silenced in GC. In
      this study, we investigated Zic1 promoter methylation in plasma DNA as a novel
      molecular marker for the early diagnosis and monitoring of GC. Methylation
      specific polymerase chain reaction (MSP) assay was performed to detect Zic1
      promoter methylation in plasma DNA from 20 healthy subjects, 50 gastric
      intraepithelial neoplasia patients, and 104 GC patients. The Zic1 promoter
      methylation rate in the plasma samples from the healthy control group was 0%, but
      it reached 54.0% in the intraepithelial neoplasia group and 60.6% in the GC
      group. The latter two values were significantly higher than that found in the
      healthy control group (p < 0.05), with a 100% specificity for intraepithelial
      neoplasia and GC diagnosis. The positive predictive value of plasma Zic1 promoter
      methylation for the diagnosis of intraepithelial neoplasia and GC was 100%.
      Methylation status in the GC group was not significantly associated with tumor
      size, tumor differentiation, lymph node metastasis, TNM staging, or tumor
      invasion (p > 0.05). Assessment of the significance of detection of the carcino
      embryonic antigen (CEA) level and Zic1 promoter methylation rate for GC diagnosis
      revealed that the sensitivity of Zic1 promoter methylation was significantly
      higher than that of the CEA level as a marker and that the combined measurement
      of these two indices (parallel testing) improved sensitivity. Taken together, our
      results suggest that the Zic1 promoter methylation rate in plasma-derived DNA is
      of great significance for the early screening of GC and monitoring of
      tumorigenesis. Zic1 promoter methylation may serve as a novel non-invasive plasma
      biomarker for the early detection of GC and for risk assessment in high-risk
      populations. The combined measurement of the Zic1 promoter methylation rate and
      CEA level (parallel testing) may enhance the current guidelines for the early
      diagnosis of GC. 

PMID- 26207912
TI  - Estimation of Life-Year Loss and Lifetime Costs for Different Stages of Colon
      Adenocarcinoma in Taiwan.
AB  - BACKGROUNDS AND AIMS: Life-expectancy of colon cancer patients cannot be
      accurately answered due to the lack of both large datasets and long-term follow
      ups, which impedes accurate estimation of lifetime cost to treat colon cancer
      patients. In this study, we applied a method to estimate life-expectancy of colon
      cancer patients in Taiwan and calculate the lifetime costs by different stages
      and age groups. METHODS: A total of 17,526 cases with pathologically verified
      colon adenocarcinoma between 2002 and 2009 were extracted from Taiwan Cancer
      Registry database for analysis. All patients were followed-up until the end of
      2011. Life-expectancy, expected-years-of-life-lost and lifetime costs were
      estimated, using a semi-parametric survival extrapolation method and borrowing
      information from life tables of vital statistics. RESULTS: Patients with more
      advanced stages of colon cancer were generally younger and less co-morbid with
      major chronic diseases than those with stages I and II. The LE of stage I was not
      significantly different from that of the age- and sex-matched general population,
      whereas those of stages II, III, and IV colon cancer patients after diagnosis
      were 16.57 +/- 0.07, 13.35 +/- 0.07, and 4.05 +/- 0.05 years, respectively; the
      corresponding expected-years-of-life-lost were 1.28 +/- 0.07, 5.93 +/- 0.07 and
      16.42 +/- 0.06 years, significantly shorter than the general population after
      accounting for lead time bias. Besides, the lifetime cost of managing stage II
      colon cancer patients would be US $8,416 +/- 1939, 14,334 +/- 1,755, and 21,837
      +/- 1,698, respectively, indicating a big saving for early diagnosis and
      treatment after stratification for age and sex. CONCLUSIONS: Treating colon
      cancer at younger age and earlier stage saves more life-years and healthcare
      costs. Future studies are indicated to apply these quantitative results into the
      cost-effectiveness evaluation of screening program for colon cancers.

PMID- 26207913
TI  - Correction: The Health Equity and Effectiveness of Policy Options to Reduce
      Dietary Salt Intake in England: Policy Forecast.

PMID- 26207914
TI  - Modeled Sea Level Rise Impacts on Coastal Ecosystems at Six Major Estuaries on
      Florida's Gulf Coast: Implications for Adaptation Planning.
AB  - The Sea Level Affecting Marshes Model (SLAMM) was applied at six major estuaries
      along Florida's Gulf Coast (Pensacola Bay, St. Andrews/Choctawhatchee Bays,
      Apalachicola Bay, Southern Big Bend, Tampa Bay and Charlotte Harbor) to provide
      quantitative and spatial information on how coastal ecosystems may change with
      sea level rise (SLR) and to identify how this information can be used to inform
      adaption planning. High resolution LiDAR-derived elevation data was utilized
      under three SLR scenarios: 0.7 m, 1 m and 2 m through the year 2100 and
      uncertainty analyses were conducted on selected input parameters at three sites.
      Results indicate that the extent, spatial orientation and relative composition of
      coastal ecosystems at the study areas may substantially change with SLR. Under
      the 1 m SLR scenario, total predicted impacts for all study areas indicate that
      coastal forest (-69,308 ha; -18%), undeveloped dry land (-28,444 ha; -2%) and
      tidal flat (-25,556 ha; -47%) will likely face the greatest loss in cover by the
      year 2100. The largest potential gains in cover were predicted for saltmarsh
      (+32,922 ha; +88%), transitional saltmarsh (+23,645 ha; na) and mangrove forest
      (+12,583 ha; +40%). The Charlotte Harbor and Tampa Bay study areas were predicted
      to experience the greatest net loss in coastal wetlands The uncertainty analyses
      revealed low to moderate changes in results when some numerical SLAMM input
      parameters were varied highlighting the value of collecting long-term
      sedimentation, accretion and erosion data to improve SLAMM precision. The changes
      predicted by SLAMM will affect exposure of adjacent human communities to coastal
      hazards and ecosystem functions potentially resulting in impacts to property
      values, infrastructure investment and insurance rates. The results and process
      presented here can be used as a guide for communities vulnerable to SLR to
      identify and prioritize adaptation strategies that slow and/or accommodate the
      changes underway. 

PMID- 26207915
TI  - Contextual Congruency Effect in Natural Scene Categorization: Different
      Strategies in Humans and Monkeys (Macaca mulatta).
AB  - Rapid visual categorization is a crucial ability for survival of many animal
      species, including monkeys and humans. In real conditions, objects (either
      animate or inanimate) are never isolated but embedded in a complex background
      made of multiple elements. It has been shown in humans and monkeys that the
      contextual background can either enhance or impair object categorization,
      depending on context/object congruency (for example, an animal in a natural vs.
      man-made environment). Moreover, a scene is not only a collection of objects; it
      also has global physical features (i.e phase and amplitude of Fourier spatial
      frequencies) which help define its gist. In our experiment, we aimed to explore
      and compare the contribution of the amplitude spectrum of scenes in the context
      object congruency effect in monkeys and humans. We designed a rapid visual
      categorization task, Animal versus Non-Animal, using as contexts both real scenes
      photographs and noisy backgrounds built from the amplitude spectrum of real
      scenes but with randomized phase spectrum. We showed that even if the contextual
      congruency effect was comparable in both species when the context was a real
      scene, it differed when the foreground object was surrounded by a noisy
      background: in monkeys we found a similar congruency effect in both conditions,
      but in humans the congruency effect was absent (or even reversed) when the
      context was a noisy background. 

PMID- 26207916
TI  - A Novel Role of E-Cadherin-Based Adherens Junctions in Neoplastic Cell
      Dissemination.
AB  - Using confocal microscopy, we analyzed the behavior of IAR-6-1, IAR1170, and
      IAR1162 transformed epithelial cells seeded onto the confluent monolayer of
      normal IAR-2 epithelial cells. Live-cell imaging of neoplastic cells stably
      expressing EGFP and of normal epithelial cells stably expressing mKate2 showed
      that transformed cells retaining expression of E-cadherin were able to migrate
      over the IAR-2 epithelial monolayer and invade the monolayer. Transformed IAR
      cells invaded the IAR-2 monolayer at the boundaries between normal cells.
      Studying interactions of IAR-6-1 transformed cells stably expressing GFP-E
      cadherin with the IAR-2 epithelial monolayer, we found that IAR-6-1 cells
      established E-cadherin-based adhesions with normal epithelial cells: dot-like
      dynamic E-cadherin-based adhesions in protrusions and large adherens junctions at
      the cell sides and rear. A comparative study of a panel of transformed IAR cells
      that differ by their ability to form E-cadherin-based AJs, either through loss of
      E-cadherin expression or through expression of a dominant negative E-cadherin
      mutant, demonstrated that E-cadherin-based AJs are key mediators of the
      interactions between neoplastic and normal epithelial cells. IAR-6-1DNE cells
      expressing a dominant-negative mutant form of E-cadherin with the mutation in the
      first extracellular domain practically lost the ability to adhere to IAR-2 cells
      and invade the IAR-2 epithelial monolayer. The ability of cancer cells to form E
      cadherin-based AJs with the surrounding normal epithelial cells may play an
      important role in driving cancer cell dissemination in the body. 

PMID- 26207917
TI  - Glioma Association and Balancing Selection of ZFPM2.
AB  - ZFPM2, encoding a zinc finger protein and abundantly expressed in the brain,
      uterus and smooth muscles, plays important roles in cardiac and gonadal
      development. Abnormal expression of ZFPM2 in ovarian tumors and neuroblastoma has
      been reported but hitherto its genetic association with cancer and effects on
      gliomas have not been studied. In the present study, the hexamer insertion
      deletion polymorphism rs71305152, located within a large haplotype block spanning
      intron 1 to intron 3 of ZFPM2, was genotyped in Chinese cohorts of glioma (n =
      350), non-glioma cancer (n = 354) and healthy control (n = 463) by direct
      sequencing and length polymorphism in gel electrophoresis, and ZFPM2 expression
      in glioma tissues (n = 69) of different grades was quantified by real-time RT
      PCR. Moreover, potential natural selection pressure acting on the gene was
      investigated. Disease-association analysis showed that the overall genotype of
      rs71305152 was significantly associated with gliomas (P = 0.016), and the
      heterozygous genotype compared to the combined homozygous genotypes was less
      frequent in gliomas than in controls (P = 0.005) or non-glioma cancers (P =
      0.020). ZFPM2 mRNA expression was negatively correlated with the grades of
      gliomas (P = 0.002), with higher expression levels in the low-grade gliomas. In
      the astrocytoma subtype, higher ZFPM2 expression was also correlated with the
      rs71305152 heterozygous genotype (P = 0.028). In addition, summary statistics
      tests gave highly positive values, demonstrating that the gene is under the
      influence of balancing selection. These findings suggest that ZFPM2 is a glioma
      susceptibility gene, its genotype and expression showing associations with
      incidence and severity, respectively. Moreover, the balancing selection acting on
      ZFPM2 may be related to the important roles it has to play in multiple organ
      development or associated disease etiology. 

PMID- 26207918
TI  - Using Standardized Interpretation of Chest Radiographs to Identify Adults with
      Bacterial Pneumonia--Guatemala, 2007-2012.
AB  - BACKGROUND: Bacterial pneumonia is a leading cause of illness and death
      worldwide, but quantifying its burden is difficult due to insensitive
      diagnostics. Although World Health Organization (WHO) protocol standardizes
      pediatric chest radiograph (CXR) interpretation for epidemiologic studies of
      bacterial pneumonia, its validity in adults is unknown. METHODS: Patients (age >=
      15 years) admitted with respiratory infections to two Guatemalan hospitals
      between November 2007 and March 2012 had urine and nasopharyngeal/oropharyngeal
      (NP/OP) swabs collected; blood cultures and CXR were also performed at physician
      clinical discretion. 'Any bacterial infection' was defined as a positive urine
      pneumococcal antigen test, isolation of a bacterial pneumonia pathogen from blood
      culture, or detection of an atypical bacterial pathogen by polymerase chain
      reaction (PCR) of nasopharyngeal/oropharyngeal (NP/OP) specimens. 'Viral
      infection' was defined as detection of viral pathogens by PCR of NP/OP specimens.
      CXRs were interpreted according to the WHO protocol as having 'endpoint
      consolidation', 'other infiltrate', or 'normal' findings. We examined
      associations between bacterial and viral infections and endpoint consolidation.
      FINDINGS: Urine antigen and/or blood culture results were available for 721
      patients with CXR interpretations; of these, 385 (53%) had endpoint consolidation
      and 253 (35%) had other infiltrate. Any bacterial infection was detected in 119
      (17%) patients, including 106 (89%) pneumococcal infections. Any bacterial
      infection (Diagnostic Odds Ratio [DOR] = 2.9; 95% confidence Interval (CI): 1.3
      7.9) and pneumococcal infection (DOR = 3.4; 95% CI: 1.5-10.0) were associated
      with 'endpoint consolidation', but not 'other infiltrate' (DOR = 1.7; 95% CI: 0.7
      4.9, and 1.7; 95% CI: 0.7-4.9 respectively). Viral infection was not
      significantly associated with 'endpoint consolidation', 'other infiltrate,' or
      'normal' findings. INTERPRETATION: 'Endpoint consolidation' was associated with
      'any bacterial infection,' specifically pneumococcal infection. Therefore,
      endpoint consolidation may be a useful surrogate for studies measuring the impact
      of interventions, such as conjugate vaccines, against bacterial pneumonia.

PMID- 26207919
TI  - Subpathway Analysis based on Signaling-Pathway Impact Analysis of Signaling
      Pathway.
AB  - Pathway analysis is a common approach to gain insight from biological
      experiments. Signaling-pathway impact analysis (SPIA) is one such method and
      combines both the classical enrichment analysis and the actual perturbation on a
      given pathway. Because this method focuses on a single pathway, its resolution
      generally is not very high because the differentially expressed genes may be
      enriched in a local region of the pathway. In the present work, to identify
      cancer-related pathways, we incorporated a recent subpathway analysis method into
      the SPIA method to form the "sub-SPIA method." The original subpathway analysis
      uses the k-clique structure to define a subpathway. However, it is not
      sufficiently flexible to capture subpathways with complex structure and usually
      results in many overlapping subpathways. We therefore propose using the minimal
      spanning-tree structure to find a subpathway. We apply this approach to
      colorectal cancer and lung cancer datasets, and our results show that sub-SPIA
      can identify many significant pathways associated with each specific cancer that
      other methods miss. Based on the entire pathway network in the Kyoto Encyclopedia
      of Genes and Genomes, we find that the pathways identified by sub-SPIA not only
      have the largest average degree, but also are more closely connected than those
      identified by other methods. This result suggests that the abnormality signal
      propagating through them might be responsible for the specific cancer or disease.

PMID- 26207920
TI  - A new lanostane-type triterpene and sesquiterpene lactones from Vernonia
      leopoldii and their in vitro cytotoxicity.
AB  - Investigation of the aerial parts of Vernonia leopoldii (Sch. Bip.) Vatke
      afforded a new lanostane-type triterpene along with known hirsutinolide-type
      sesquiterpene lactones and flavonoid glycosides, all are identified for the first
      time in this species. The new compound was identified as lanost-3beta, 23S
      dihydroxy-22(31)-ene. The structures of the isolated compounds were elucidated
      based on spectroscopic evidence. The hirsutinolides and the triterpene were
      evaluated for their cytotoxicity against four human cancer cell lines using MTT
      assay. 

PMID- 26207922
TI  - Predictive modeling and threshold scores for care seeking among women with
      urinary incontinence: The short forms of the Pelvic Floor Distress Inventory and
      Urogenital Distress Inventory.
AB  - AIMS: To further the interpretability of the Pelvic Floor Distress Inventory
      (PFDI-20) and Urogenital Distress Inventory (UDI-6) by (i) evaluating the ability
      of these measures to distinguish between women with urinary incontinence who do
      and do not seek care, (ii) defining PFDI-20 and UDI-6 threshold scores above
      which women with urinary incontinence seek care, and (iii) developing a
      predictive model for incontinence care seeking. METHODS: An observational study
      was conducted with two groups of women with urinary incontinence: 256 who had not
      sought care and 90 seeking initial care at a tertiary center. Sample sizes were
      based upon the prevalence of care seeking for urinary incontinence and the number
      of potential predictors for care seeking. Wilcoxon rank-sum tests, receiver
      operating characteristics, and multivariable logistic regression were use to
      achieve the study aims. RESULTS: Women with urinary incontinence who sought care
      had higher median PFDI-20 and UDI-6 scores compared to non-care seekers (73.96
      vs. 16.67, P < 0.0001, and 41.67 vs. 8.33, P < 0.0001). A PFDI-20 score of 33.33
      (83.33% sensitivity and 79.30% specificity) had very good discriminatory accuracy
      in distinguishing care and non-care seekers (AUC 0.886 +/- 0.019 [95%CI 0.8518,
      0.9254] P < 0.0001). A UDI-6 score of 25.00 (83.33% sensitivity and 83.59%
      specificity) had excellent discriminatory accuracy in distinguishing care and non
      care seekers (AUC 0.9025 +/- 0.0190 [95%CI 0.8653, 0.9398] P < 0.0001). A
      multivariable predictive model accurately identified 82.4% of care and non-care
      seekers. CONCLUSIONS: A PFDI-20 score of 33.33 and UDI-6 score of 25.00 provide
      meaningful benchmarks for care seeking among women with urinary incontinence.
      Neurourol. Urodynam. 35:949-954, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26207923
TI  - Correction: Non-Invasive Delivery of dsRNA into De-Waxed Tick Eggs by
      Electroporation.

PMID- 26207921
TI  - MicroRNA-124 and -137 cooperativity controls caspase-3 activity through BCL2L13
      in hippocampal neural stem cells.
AB  - Adult neurogenesis continuously contributes new neurons to hippocampal circuits
      and the programmed death of a subset of immature cells provides a primary
      mechanism controlling this contribution. Epileptic seizures induce strong
      structural changes in the hippocampus, including the induction of adult
      neurogenesis, changes in gene expression and mitochondrial dysfunction, which may
      all contribute to epileptogenesis. However, a possible interplay between this
      factors remains largely unexplored. Here, we investigated gene expression changes
      in the hippocampal dentate gyrus shortly after prolonged seizures induced by
      kainic acid, focusing on mitochondrial functions. Using comparative proteomics,
      we identified networks of proteins differentially expressed shortly after seizure
      induction, including members of the BCL2 family and other mitochondrial proteins.
      Within these networks, we report for the first time that the atypical BCL2
      protein BCL2L13 controls caspase-3 activity and cytochrome C release in neural
      stem/progenitor cells. Furthermore, we identify BCL2L13 as a novel target of the
      cooperative action of microRNA-124 and microRNA-137, both upregulated shortly
      after seizure induction. This cooperative microRNA-mediated fine-tuning of
      BCL2L13 expression controls casp3 activity, favoring non-apoptotic caspase-3
      functions in NSPC exposed to KA and thereby may contribute to the early
      neurogenic response to epileptic seizures in the dentate gyrus. 

PMID- 26207924
TI  - Challenges and Opportunities in the Discovery of New Therapeutics Targeting the
      Kynurenine Pathway.
AB  - The kynurenine pathway is responsible for the metabolism of more than 95% of
      dietary tryptophan (TRP) and produces numerous bioactive metabolites. Recent
      studies have focused on three enzymes in this pathway: indoleamine dioxygenase
      (IDO1), kynurenine monooxygenase (KMO), and kynurenine aminotransferase II (KAT
      II). IDO1 inhibitors are currently in clinical trials for the treatment of
      cancer, and these agents may also have therapeutic utility in neurological
      disorders, including multiple sclerosis. KMO inhibitors are being investigated as
      potential treatments for neurodegenerative diseases, such as Huntington's and
      Alzheimer's diseases. KAT II inhibitors have been proposed in new therapeutic
      approaches toward psychiatric and cognitive disorders, including cognitive
      impairment associated with schizophrenia. Numerous medicinal chemistry studies
      are currently aimed at the design of novel, potent, and selective inhibitors for
      each of these enzymes. The emerging opportunities and significant challenges
      associated with pharmacological modulation of these enzymes will be explored in
      this review. 

PMID- 26207925
TI  - An instrument-free, screen-printed paper microfluidic device that enables bio and
      chemical sensing.
AB  - This paper describes a simple and instrument-free screen-printing method to
      fabricate hydrophilic channels by patterning polydimethylsiloxane (PDMS) onto
      chromatography paper. Clearly recognizable border lines were formed between
      hydrophilic and hydrophobic areas. The minimum width of the printed channel to
      deliver an aqueous sample was 600 MUm, as obtained by this method. Fabricated
      microfluidic paper-based analytical devices (MUPADs) were tested for several
      colorimetric assays of pH, glucose, and protein in both buffer and artificial
      urine samples and results were obtained in less than 30 min. The limits of
      detection (LODs) for glucose and bovine serum albumin (BSA) were 5 mM and 8 MUM,
      respectively. Furthermore, the pH values of different solutions were visually
      recognised with the naked eye by using a sensitive ink. Ultimately, it is
      expected that this PDMS-screen-printing (PSP) methodology for MUPADs can be
      readily translated to other colorimetric detection and hydrophilic channels
      surrounded by a hydrophobic polymer can be formed to transport fluids toward
      target zones. 

PMID- 26207926
TI  - Systematic Enumeration of sp(3) Nanothreads.
AB  - Slow decompression of crystalline benzene in large-volume high-pressure cells has
      recently achieved synthesis of a novel one-dimensional allotrope of sp(3) carbon
      in which stacked columns of benzene molecules rehybridize into an ordered crystal
      of nanothreads. The progenitor benzene molecules function as six-valent one
      dimensional superatoms with multiple binding sites. Here we enumerate their
      hexavalent bonding geometries, recognizing that the repeat unit of interatomic
      connectivity ("topological unit cell") need not coincide with the
      crystallographic unit cell, and identify the most energetically favorable cases.
      A topological unit cell of one or two benzene rings with at least two bonds
      interconnecting each adjacent pair of rings, accommodates 50 topologically
      distinct nanothreads, 15 of which are within 80 meV/carbon atom of the most
      stable member. Optimization of aperiodic helicity reveals the most stable
      structures to be chiral. We generalize Euler's rules for ring counting to cover
      this new form of very thin one-dimensional carbon, calculated their physical
      properties, and propose a naming convention that can be generalized to handle
      nanothreads formed from other progenitor molecules. 

PMID- 26207928
TI  - Contrast Media for X-ray and Magnetic Resonance Imaging: Development, Current
      Status and Future Perspectives.
AB  - Over the last 120 years, the extensive advances in medical imaging allowed
      enhanced diagnosis and therapy of many diseases and thereby improved the quality
      of life of many patient generations. From the beginning, all technical solutions
      and imaging procedures were combined with dedicated pharmaceutical developments
      of contrast media, to further enhance the visualization of morphology and
      physiology. This symbiosis of imaging hardware and contrast media development was
      of high importance for the development of modern clinical radiology. Today, all
      available clinically approved contrast media fulfill the highest requirements for
      clinical safety and efficacy. All new concepts to increase the efficacy of
      contrast media have also to consider the high clinical safety standards and cost
      of goods of current marketed contrast media. Nevertheless, diagnostic imaging
      will contribute significantly to the progresses in medicine, and new contrast
      media developments are mandatory to address the medical needs of the future. 

PMID- 26207927
TI  - The Role of Adjunctive Therapies in the Management of Invasive Sino-Orbital
      Infection.
AB  - OBJECTIVE: Invasive sino-orbital fungal infections are life-threatening
      complications of immunonosupression that are difficult to treat. Currently there
      are no standard treatment guidelines. The most widely accepted therapy includes
      parenteral anti-fungal therapy and surgical debridement of sinuses with orbital
      exenteration, a procedure that is not only disfiguring, but may increase
      morbidity. Injection of retrobulbar Liposomal Amphotericin B (L-AMB) is an
      alternative approach that provides local administration to infected tissues. The
      adjunct use of anti-fungal retrobulbar injections not been extensively reviewed
      in treating sino-orbital infection. We are reporting the multimodal approach of
      using L-AMB retrobulbar injections in combination with sinus debridement,
      intravenous (IV) anti-fungal therapy, and hyperbaric oxygen (HBO) for the
      management of sino-orbital infection. METHOD & RESULTS: Review of literature of
      12 cases and retrospective evaluation of one patient with sino-orbital
      Aspergillus flavus infection on chemotherapy for T-cell acute lymphocytic
      leukemia treated with retrobulbar Amphotericin B, IV anti-fungal agents, and
      hyperbaric oxygen therapy. Clinical characteristics, radiographic features,
      management techniques, and clinical outcomes are described. CONCLUSION:
      Retrobulbar Amphotericin B injection may be an effective adjunct to hyperbaric
      oxygen and parenteral anti-fungals in the control of sino-orbital fungal
      infections.

PMID- 26207929
TI  - Exopolysaccharides Produced by Leuconostoc mesenteroides Strain NTM048 as an
      Immunostimulant To Enhance the Mucosal Barrier and Influence the Systemic Immune
      Response.
AB  - Leuconostoc mesenteroides strain NTM048 has been shown to have intestinal IgA
      inducing ability. In this study, we investigated the immunostimulant potency of
      an exopolysaccharide secreted from strain NTM048 (NTM048 EPS) in vitro and in
      vivo in a murine model. NTM048 EPS ranges in size from 10 to 40 kDa and is
      speculated to be mainly composed of glucose and fructose. The in vitro study
      revealed that NTM048 EPS induced total and antigen-specific IgA production by
      Peyer's patch cells and influenced Th1 and Th2 cell-mediated response in
      splenocytes. Oral administration of NTM048 EPS dose-dependently induced fecal IgA
      production accompanied by the up-regulation of retinoic acid synthase and
      transforming growth factor-beta receptor genes in Peyer's patch cells. Flow
      cytometric analysis of the splenocytes revealed an increase of the CD3+ T-cell
      population and the ratio of CD4+ T-cells/CD8+ T-cells. These results indicate
      that NTM048 EPS could enhance the mucosal barrier and influence the systemic
      immune response. 

PMID- 26207930
TI  - Tunable Luminescence and Application in Dye-Sensitized Solar Cells of
      Zn(II)/Hg(II) Complexes: Methyl Substitution-Induced Supramolecular Structures
      Based on (E)-N-(6-Methoxypyridin-2-ylmethylene)arylamine Derivatives.
AB  - Using Schiff-base ligands (E)-N-(6-methoxypyridin-2-yl)(CH?NAr) (where Ar = C6H5,
      L1; 2-MeC6H4, L2; 2,4,6-Me3C6H2, L3), six Zn(II)/Hg(II) complexes, namely,
      [ZnL1Cl2] (Zn1), [HgL1Cl2] (Hg1), [ZnL2Cl2] (Zn2), [HgL2Cl2] (Hg2), [ZnL3Cl2]
      (Zn3), and [HgL3Cl2] (Hg3) have been synthesized under solvothermal conditions.
      The structures of six complexes have been established by X-ray single-crystal
      analysis and further physically characterized by EA, FT-IR, (1)H NMR, and ESI-MS.
      The crystal structures of these complexes indicate that noncovalent interactions,
      such as hydrogen bonds, C-H...Cl, and pi...pi stacking, play essential roles in
      constructing the resulting supramolecular structures (1D for Hg3; 2D for Zn2,
      Hg2; 3D for Zn1, Hg1, and Zn3). Upon irradiation with UV light, the emission of
      complexes Zn1-Zn3 and Hg1-Hg3 could be finely tuned from green (480-540 nm) in
      the solid state to blue (402-425 nm) in acetonitrile solution. It showed that the
      ligand and metal cation can influence the structures and luminescence properties
      of complexes such as emission intensities and maximum wavelengths. Since these
      ligands and complexes could compensate for the absorption of N719 in the low
      wavelength region of the visible spectrum and reduce charge recombination of the
      injected electron, the ligands L1-L3 and complexes Zn3/Hg3 were employed to
      prepare cosensitized dye-sensitized solar cells devices for investigating the
      influences of the electron-donating group and coordination on the DSSCs
      performance. Compared to DSSCs only being sensitized by N719, these prepared
      ligands and complexes chosen to cosensitize N719 in solar cell do enhanced its
      performance by 11-41%. In particular, a DSSC using L3 as cosensitizer displays
      better photovoltaic performance with a short circuit current density of 18.18 mA
      cm(-2), corresponding to a conversion efficiency of 7.25%. It is much higher than
      that for DSSCs only sensitized by N719 (5.14%). 

PMID- 26207932
TI  - Differential regulation of pericyte function by the CXC receptor 3.
AB  - Pericytes are mural cell that have been found to play important roles in
      promoting blood vessel development and regulating blood flow. The signals that
      attract pericytes to maturing vessels during the resolution phase of wound
      healing are unknown. In this study, we examine the role of the chemokine receptor
      CXC receptor 3 (CXCR3) ligands, as they are produced by maturing endothelial
      cells. Pericytes isolated from muscle and retina were found to by and large only
      express the B-isoform of CXCR3 (CXCR3B), with expression being independent of the
      mitotic state of the cells. Pericyte stimulation with the CXCR3 ligands Mig
      (CXCL9), IP-9/I-TAC (CXCL11), or IP-10 (CXCL10) resulted in the activation of ERK
      but not AKT. Treatment with Mig or IP-9, but not IP-10, enhanced p38(MAPK)
      phosphorylation. Interestingly, while cyclic adenosine monophosphate is generated
      downstream of CXCR3B in other cells, protein kinase A activation was not observed
      in these pericytes when treated with these three CXCR3 ligands. The increase in
      ERK activity resulted in a slight increase in cell transmigration, with the
      inhibition of ERK leading to a decrease in CXCR3B mediated migration and
      inhibition of p38(MAPK) reducing transmigration through small pores. These
      ligands did not affect proliferation. These data are the first to characterize
      CXCR3B as the predominant isoform expressed on pericytes, and was found on these
      diverse cells isolated from both muscle and eye. We also show that CXCR3B
      signaling stimulates transmigration of barrier pores in pericytes as opposed to
      its inhibitory affects on endothelial cells and fibroblasts. These findings
      characterize a novel role for the CXCR3B in regulating cellular function. Taken
      together these data show a role for CXCR3B in regulating pericyte function. 

PMID- 26207934
TI  - Waterborne Colloidal Polymer/Silica Hybrid Dispersions and Their Assembly into
      Mesoporous Poly(melamine-formaldehyde) Xerogels.
AB  - The acid-catalyzed polycondensation of oligo(melamine-formaldehyde) in aqueous
      phase and in the presence of silica nanoparticles leads to a stable dispersion of
      coexisting silica and polymer nanoparticles. The dispersion can be processed into
      mesoporous xerogels (SBET ~ 200 m(2) g(-1)), whose porosity can be enhanced by
      etching of silica up to specific surface areas of >400 m(2) g(-1). The formation
      mechanism and the characteristics of the hybrid dispersion are crucial to the
      materials derived from it and analyzed in detail using a variety of experimental
      techniques (electron and force microscopy, light and X-ray scattering,
      ultracentrifugation, and spectroscopy). The transformation of the dispersion into
      xerogels by electrostatic destabilization is described. Furthermore, the obtained
      materials are characterized with regard to their porosity and morphology using
      microscopy and porosimetry. The impact of selected synthesis parameters on the
      obtained properties is discussed, and it was found (most interestingly) that
      stable porosity was only observed if silica nanoparticles were present within the
      dispersion. 

PMID- 26207933
TI  - Practical aspects of DDAVP use in patients with von Willebrand Disease undergoing
      invasive procedures: a European survey.
AB  - INTRODUCTION: Desamino D-arginine vasopressin (DDAVP or desmopressin) is a useful
      and effective haemostatic treatment for patients with von Willebrand Disease
      (VWD). However, there are still issues regarding in which subtypes of VWD DDAVP
      is appropriate and little consensus on its use in different surgical settings. We
      also lack information concerning the appropriate laboratory parameters that
      should be monitored. AIM: The European Haemophilia Therapy Strategy Board (EHTSB)
      wished to investigate published information and clinical use of DDAVP in VWD
      patients. METHODS: We conducted a literature survey on management of VWD during
      surgical interventions and undertook a survey of specialist haematologist centres
      across Europe to assess current management of VWD patients. RESULTS: DDAVP is
      ineffective in type 3 VWD and its use in type 2B remains controversial due to the
      possibility of thrombocytopenia. It can, however, be used effectively to cover
      minor surgery and dental procedures in most other VWD patients. For major surgery
      there is wider use of factor concentrate in preference to DDAVP depending on the
      subtype of VWD. We give consensus recommendations on the use of DDAVP for
      surgical interventions in VWD including laboratory parameters that denote an
      adequate response and contraindications to its use. CONCLUSIONS: DDAVP can be
      recommended to cover invasive procedure in selected patients with VWD, however,
      we need more information and systematic recording of adverse events associated
      with DDAVP use in VWD. A companion paper will be published covering the use of
      factor concentrates in VWD patients.

PMID- 26207935
TI  - Noninvasive tracking of gene transcript and neuroprotection after gene therapy.
AB  - Gene therapy holds exceptional potential for translational medicine by improving
      the products of defective genes in diseases and/or providing necessary biologics
      from endogenous sources during recovery processes. However, validating methods
      for the delivery, distribution and expression of the exogenous genes from such
      therapy can generally not be applicable to monitor effects over the long term
      because they are invasive. We report here that human granulocyte colony
      stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self
      complementary adeno-associated virus-type 2 adeno-associated virus, as delivered
      through eye drops at multiple time points after cerebral ischemia using bilateral
      carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality
      rates, cerebral atrophy and neurological deficits in C57black6 mice. Most
      importantly, we validated hG-CSF cDNA expression using translatable magnetic
      resonance imaging (MRI) in living brains. This noninvasive approach for
      monitoring exogenous gene expression in the brains has potential for great impact
      in the area of experimental gene therapy in animal models of heart attack,
      stroke, Alzheimer's dementia, Parkinson's disorder and amyotrophic lateral
      sclerosis, and the translation of such techniques to emergency medicine. 

PMID- 26207936
TI  - Pancreatic cystic lesions with atypical steroid response should be carefully
      managed in cases of autoimmune pancreatitis.
AB  - BACKGROUND AND AIM: Pancreatic cysts have been reported in cases with autoimmune
      pancreatitis (AIP) and are often treated by corticosteroid; however, their
      response to steroid has not been determined fully. We aimed to see the incidence
      and steroid response of pancreatic cysts and the features of cysts without proper
      response in cases with AIP. METHODS: Fifty-eight AIP cases were analyzed for the
      incidence and associated factors of pancreatic cystic lesions (>= 10 mm). Of
      these, 47 cases, determined for steroid response, were retrospectively
      investigated for the factors associated with cyst change by corticosteroid
      therapy. RESULTS: At initial diagnosis, 17 pancreatic cystic lesions were
      recognized in 13 cases (22.4%) of AIP, with an average size of 30 mm (range: 11
      130 mm), associated with higher incidence of elevated serum amylase (38.5% vs
      11.1%, P = 0.02). Of these 13 cases, nine cases with 10 cystic lesions underwent
      steroid therapy in our hospital. All of seven unilocular cysts were dramatically
      shrunken or vanished in a few months; meanwhile, three cases with multilocular
      cysts showed scarcely any steroid response (P = 0.008). Of these three cases, two
      cases were revealed to accompany pancreatic ductal carcinoma, in contrast to null
      of seven unilocular cysts (P = 0.07). CONCLUSIONS: Pancreatic cystic lesions are
      sometimes recognized in cases with AIP, and most unilocular cysts can be
      minimized by corticosteroids. However, clinicians must be alert for atypical
      pancreatic cysts, such as multilocular cysts or cysts without obvious steroid
      response.

PMID- 26207937
TI  - The structural and mutational analyses of O-ureido-L-serine synthase necessary
      for D-cycloserine biosynthesis.
AB  - We have recently been successful in cloning a gene cluster necessary for the
      biosynthesis of D-cycloserine (D-CS) from D-CS-producing Streptomyces lavendulae
      ATCC11924. Although dcsD, one of the ORFs located on the gene cluster, encodes a
      protein homologous to O-acetylserine sulfhydrylase that synthesizes L-cysteine
      using O-acetyl-L-serine together with sulfide, it functions to form O-ureido-L
      serine as a D-CS biosynthetic intermediate, using O-acetyl-L-serine together with
      hydroxyurea (HU). In the present study, using crystallographic and mutational
      studies, three amino acid residues in DcsD that are important for the substrate
      preference toward HU were determined. We showed that two of the three residues
      are important for the binding of HU into the substrate-binding pocket. The other
      residue contributes to the formation of a loose hydrogen-bond network during the
      catalytic reaction. Information regarding the amino acid residues will be very
      useful in the design of a new catalyst for synthesizing the beta-substituted-L
      alanine derivatives. DATABASE: The atomic coordinates and structure factors of
      wild-type DcsD and l-OUS-bound K43A mutant of DcsD have been deposited in the
      Protein Data Bank under accession codes 3X43 and 3X44, respectively.

PMID- 26207938
TI  - Comment on "Appalachian Mountaintop Mining Particulate Matter Induces Neoplastic
      Transformation of Human Bronchial Epithelial Cells and Promotes Tumor Formation".

PMID- 26207939
TI  - Whole-genome shotgun sequence assembly enables rapid gene characterization in the
      tropical fish barramundi, Lates calcarifer.

PMID- 26207940
TI  - Corrigendum.

PMID- 26207941
TI  - Erratum.

PMID- 26207942
TI  - ?

PMID- 26207944
TI  - A BODIPY-based 'turn-on' fluorescent probe for hypoxic cell imaging.
AB  - A boron-dipyrromethene (BODIPY) dye containing a styryl substituent with a
      hydroxyl and nitro group, 1a, exhibits a 'turn-on' fluorescence response for
      hypoxic cells. The presence of the electron-withdrawing nitro group results in a
      highly efficient nonradiative decay of the S1 state, and hence a recovery of
      fluorescence intensity when nitro reduction occurs under hypoxic conditions. 

PMID- 26207945
TI  - 1,3-Diiodobenzene on Cu(111)--an exceptional case of on-surface Ullmann coupling.
AB  - Ullmann coupling of 1,3-diiodobenzene is studied on Cu(111) surfaces in ultra
      high vacuum (UHV). In situ Scanning Tunneling Microscopy (STM) at room
      temperature revealed an unexpected ordered arrangement of highly uniform reaction
      products adsorbed atop a closed iodine monolayer. 

PMID- 26207946
TI  - The effect of anatomical factors on mortality rates after endovascular aneurysm
      repair.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of
      anatomical characteristics on mortality rates after endovascular aneurysm repair
      (EVAR). METHODS: We investigated 56 EVAR procedures for infrarenal aortic
      aneurysms performed between January 2010 and December 2013, and the data were
      supplemented with a prospective review. The patients were divided into two groups
      according to the diameter of the aneurysm. Group I (n = 30): patients with
      aneurysm diameters less than 6 cm, group II (n = 26): patients with aneurysm
      diameters larger than 6 cm. The pre-operative anatomical data of the aneurysms
      were noted and the groups were compared with regard to postoperative results.
      RESULTS: There were no correlations between diameter of aneurysm (p > 0.05),
      aneurysm neck angle (p > 0.05) and mortality rate. The long-term mortality rate
      was found to be high in patients in whom an endoleak occurred. CONCLUSION: We
      found that aneurysm diameter did not have an effect on postoperative mortality
      rates. An increased EuroSCORE value and the development of endoleaks had an
      effect on long-term mortality rates.

PMID- 26207947
TI  - Population size is weakly related to quantitative genetic variation and trait
      differentiation in a stream fish.
AB  - How population size influences quantitative genetic variation and differentiation
      among natural, fragmented populations remains unresolved. Small, isolated
      populations might occupy poor quality habitats and lose genetic variation more
      rapidly due to genetic drift than large populations. Genetic drift might
      furthermore overcome selection as population size decreases. Collectively, this
      might result in directional changes in additive genetic variation (VA ) and trait
      differentiation (QST ) from small to large population size. Alternatively, small
      populations might exhibit larger variation in VA and QST if habitat fragmentation
      increases variability in habitat types. We explored these alternatives by
      investigating VA and QST using nine fragmented populations of brook trout varying
      50-fold in census size N (179-8416) and 10-fold in effective number of breeders,
      Nb (18-135). Across 15 traits, no evidence was found for consistent differences
      in VA and QST with population size and almost no evidence for increased
      variability of VA or QST estimates at small population size. This suggests that
      (i) small populations of some species may retain adaptive potential according to
      commonly adopted quantitative genetic measures and (ii) populations of varying
      sizes experience a variety of environmental conditions in nature, however
      extremely large studies are likely required before any firm conclusions can be
      made. 

PMID- 26207948
TI  - Risky Drinking, Alcohol Use Disorders, and Health Services Utilization in the
      U.S. General Population: Data from the 2005 and 2010 National Alcohol Surveys.
AB  - BACKGROUND: While alcohol-related problems have been found to be overrepresented
      in clinical samples of patients, less is known about health services utilization
      in the general population. METHODS: To explore the association of risky drinking
      and alcohol use disorders (AUD) with inpatient and outpatient services
      utilization, data are analyzed from a merged sample of 13,165 respondents in the
      2005 and 2010 U.S. National Alcohol Surveys. Propensity score weighting was used
      to minimize potential bias associated with the heterogeneity in individual-level
      characteristics across respondents which might influence these relationships.
      RESULTS: No significant differences were found between risky and nonrisky
      drinkers on any of the utilization variables in the last year, with 11% reporting
      an emergency room (ER) visit, a third reporting a primary care visit, and 6.2 to
      7.6% reporting hospitalization. Those with an AUD were significantly more likely
      than those without to report an ER visit in the last year (18.2% vs. 11.6%; p =
      0.003) as well as a greater number of such visits (p = 0.007), and to report more
      primary care visits (p = 0.05) and any hospitalization (11.2% vs. 6.7%; p =
      0.019). CONCLUSIONS: The data suggest a significant and potentially costly
      increase in health services utilization due to AUD. ERs and primary care settings
      would benefit from devoting increased resources to addressing AUD, which could
      result in clinical benefits of improvement in overall health status as well as
      economic benefits in lowering healthcare costs for both patients and society as a
      whole.

PMID- 26207950
TI  - Pulse height tests of a large diameter fast LaBr3:Ce scintillation detector.
AB  - The pulse height response of a large diameter fast 100 mm * 100 mm LaBr3:Ce
      detector was measured for 0.1-10 MeV gamma-rays. The detector has a claimed time
      resolution of 608 ps for 511 keV gamma rays, but has relatively poor energy
      resolution due to the characteristics of its fast photomultiplier. The detector
      pulse height response was measured for gamma rays from cobalt, cesium, and
      bismuth radioisotope sources as well as prompt gamma rays from thermal neutron
      capture in water samples contaminated with mercury (3.1 wt%), boron (2.5 wt%),
      cadmium (0.25 wt%), chromium (52 wt%), and nickel (22 wt%) compounds. The energy
      resolution of the detector was determined from full width at half maximum (FWHM)
      of element-characteristic gamma ray peaks in the pulse height spectrum associated
      with the element present in the contaminated water sample. The measured energy
      resolution of the 100 mm * 100 mm detector varies from 12.7+/-0.2% to 1.9+/-0.1%
      for 0.1 to 10 MeV gamma rays, respectively. The graph showing the energy
      resolution DeltaE/E(%) versus 1/?Egamma was fitted with a linear function to
      study the detector light collection from the slope of the curve. The slope of the
      present 100 mm * 100 mm detector is almost twice as large as the slope of a
      similar curve of previously published data for a 89 mm * 203 mm LaBr3:Ce
      detector. This indicates almost two times poorer light collection in the 100 mm *
      100 mm detector as compared to the other detector.

PMID- 26207949
TI  - Histone lysine demethylases in Drosophila melanogaster.
AB  - Epigenetic regulation of chromatin structure is a fundamental process for
      eukaryotes. Regulators include DNA methylation, microRNAs and chromatin
      modifications. Within the chromatin modifiers, one class of enzymes that can
      functionally bind and modify chromatin, through the removal of methyl marks, is
      the histone lysine demethylases. Here, we summarize the current findings of the
      13 known histone lysine demethylases in Drosophila melanogaster, and discuss the
      critical role of these histone-modifying enzymes in the maintenance of genomic
      functions. Additionally, as histone demethylase dysregulation has been identified
      in cancer, we discuss the advantages for using Drosophila as a model system to
      study tumorigenesis. 

PMID- 26207951
TI  - Aquaporins and Fetal Membranes From Diabetic Parturient Women: Expression
      Abnormalities and Regulation by Insulin.
AB  - CONTEXT: During pregnancy, aquaporins (AQPs) expressed in fetal membranes are
      essential for controlling the homeostasis of the amniotic volume, but their
      regulation by insulin was never explored in diabetic women. OBJECTIVE: The aim of
      our study was to investigate the involvement of AQPs 1, 3, 8, and 9 expressed in
      fetal membranes in diabetic parturient women and the control of their expression
      by insulin. DESIGN AND PARTICIPANTS: From 129 fetal membranes in four populations
      (controls, type 1, type 2 [T2D], and gestational diabetes [GD]), we established
      an expression AQP profile. In a second step, the amnion was used to study the
      control of the expression and functions of AQPs 3 and 9 by insulin. MAIN OUTCOMES
      AND MEASURES: The expression of transcripts and proteins of AQPs was studied by
      quantitative RT-PCR and ELISA. We analyzed the regulation by insulin of the
      expression of AQPs 3 and 9 in the amnion. A tritiated glycerol test enabled us to
      measure the impact of insulin on the functional characteristics. Using an
      inhibitor of phosphatidylinositol 3-kinase, we analyzed the insulin intracellular
      signaling pathway. RESULTS: The expression of AQP3 protein was significantly
      weaker in groups T2D and GD. In nondiabetic fetal membranes, we showed for the
      amnion (but not for the chorion) a significant repression by insulin of the
      transcriptional expression of AQPs 3 and 9, which was blocked by a
      phosphatidylinositol 3-kinase inhibitor. CONCLUSION: In fetal membranes, the
      repression of AQP3 protein expression and functions observed in vivo is allowed
      by the hyperinsulinism described in pregnant women with T2D or GD.

PMID- 26207952
TI  - Expanding the Spectrum of Founder Mutations Causing Isolated Gonadotropin
      Releasing Hormone Deficiency.
AB  - CONTEXT: Loss of function (LoF) mutations in more than 20 genes are now known to
      cause isolated GnRH deficiency (IGD) in humans. Most causal IGD mutations are
      typically private, ie, limited to a single individual/pedigree. However, somewhat
      paradoxically, four IGD genes (GNRH1, TAC3, PROKR2, and GNRHR) have been shown to
      harbor LoF founder mutations that are shared by multiple unrelated individuals.
      It is not known whether similar founder mutations occur in other IGD genes.
      OBJECTIVE: The objective of the study was to determine whether shared deleterious
      mutations in IGD-associated genes represent founder alleles. SETTING: This study
      was an international collaboration among academic medical centers. METHODS: IGD
      patients with shared mutations, defined as those documented in three or more
      unrelated probands in 14 IGD-associated genes, were identified from various
      academic institutions, the Human Gene Mutation Database, and literature reports
      by other international investigators. Haplotypes of single-nucleotide
      polymorphisms and short tandem repeats surrounding the mutations were constructed
      to assess genetic ancestry. RESULTS: A total of eight founder mutations in five
      genes, GNRHR (Q106R, R262Q, R139H), TACR3 (W275X), PROKR2 (R85H), FGFR1 (R250Q,
      G687R), and HS6ST1 (R382W) were identified. Most founder alleles were present at
      low frequency in the general population. The estimated age of these mutant
      alleles ranged from 1925 to 5600 years and corresponded to the time of rapid
      human population expansion. CONCLUSIONS: We have expanded the spectrum of founder
      alleles associated with IGD to a total of eight founder mutations. In contrast to
      the approximately 9000-year-old PROKR2 founder allele that may confer a
      heterozygote advantage, the rest of the founder alleles are relatively more
      recent in origin, in keeping with the timing of recent human population expansion
      and any selective heterozygote advantage of these alleles requires further
      evaluation.

PMID- 26207953
TI  - MAFA and T3 Drive Maturation of Both Fetal Human Islets and Insulin-Producing
      Cells Differentiated From hESC.
AB  - CONTEXT: Human embryonic stem cells (hESCs) differentiated toward beta-cells and
      fetal human pancreatic islet cells resemble each other transcriptionally and are
      characterized by immaturity with a lack of glucose responsiveness, low levels of
      insulin content, and impaired proinsulin-to-insulin processing. However, their
      response to stimuli that promote functionality have not been compared. OBJECTIVE:
      The objective of the study was to evaluate the effects of our previous strategies
      for functional maturation developed in rodents in these two human models of beta
      cell immaturity and compare their responses. Design, Settings, Participants, and
      Interventions: In proof-of-principle experiments using either adenoviral-mediated
      overexpression of V-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog A
      (MAFA) or the physiologically driven path via thyroid hormone (T3) and human
      fetal islet-like cluster (ICC) functional maturity was evaluated. Then the
      effects of T3 were evaluated upon the functional maturation of hESCs
      differentiated toward beta-cells. MAIN OUTCOME MEASURES: Functional maturation
      was evaluated by the following parameters: glucose responsiveness, insulin
      content, expression of the mature beta-cell transcription factor MAFA, and
      proinsulin-to-insulin processing. RESULTS: ICCs responded positively to MAFA
      overexpression and T3 treatment as assessed by two different maturation
      parameters: increased insulin secretion at 16.8 mM glucose and increased
      proinsulin-to-insulin processing. In hESCs differentiated toward beta-cells, T3
      enhanced MAFA expression, increased insulin content (probably mediated by the
      increased MAFA), and increased insulin secretion at 16.8 mM glucose. CONCLUSION:
      T3 is a useful in vitro stimulus to promote human beta-cell maturation as shown
      in both human fetal ICCs and differentiated hESCs. The degree of maturation
      induced varied in the two models, possibly due to the different developmental
      status at the beginning of the study.

PMID- 26207954
TI  - Hydrophilic Carboxyl Cotton Chelator for Titanium(IV) Immobilization and Its
      Application as Novel Fibrous Sorbent for Rapid Enrichment of Phosphopeptides.
AB  - Sample preparation methods with high selectivity, efficiency, and matrix
      resistance are essential for phosphoproteomic analysis. In this study, carboxyl
      cotton chelator-titanium(IV) (CCC-Ti4+) fibers, a novel CCC-based fibrous sorbent
      with excellent biocompatibility, were successfully synthesized on the basis of
      the coordination effect between double carboxyl groups on CCC and Ti4+. The
      synthesis of CCC-Ti4+ fibers was easy, and the incorporated titanium content was
      high. On the basis of immobilized metal ion affinity chromatography (IMAC), CCC
      Ti4+ fibers were used for specific capture of phosphopeptides using a lab-in
      syringe solid-phase extraction (SPE) from multiple biological samples, including
      standard protein digests, nonfat milk digests, human serum, and animal tissue.
      The proposed sorbent exhibited high selectivity (beta-casein/BSA=1:1000) and good
      sensitivity (10 fmol) in phosphopeptides analysis. Meanwhile, the lab-in-syringe
      SPE greatly simplified the entire process of enrichment. Thanks to the good
      biocompatibility of CCC-based material, CCC-Ti4+ fibers showed excellent
      performance in phosphopeptide enrichment from protein-rich human serum. Finally,
      CCC-Ti4+ fibers were applied for selective capture of phosphopeptides from
      tryptic digests of rat brain lysate followed by LC-MS/MS analysis. Using the
      proposed method, we identified 3950 unique phosphosites from 1 mg of rat brain in
      a single experiment, which is much better than previously reported IMAC-based
      strategies. Taken together, this efficient method will find broad application in
      large-scale phosphoproteomics analysis because of the rapid (3 min) convenient
      procedure and excellent performance.

PMID- 26207955
TI  - Negation in context: Evidence from the visual world paradigm.
AB  - Literature assumes that negation is more difficult to understand than
      affirmation, but this might depend on the pragmatic context. The goal of this
      paper is to show that pragmatic knowledge modulates the unfolding processing of
      negation due to the previous activation of the negated situation. To test this,
      we used the visual world paradigm. In this task, we presented affirmative (e.g.,
      her dad was rich) and negative sentences (e.g., her dad was not poor) while
      viewing two images of the affirmed and denied entities. The critical sentence in
      each item was preceded by one of three types of contexts: an inconsistent context
      (e.g., She supposed that her dad had little savings) that activates the negated
      situation (a poor man), a consistent context (e.g., She supposed that her dad had
      enough savings) that activates the actual situation (a rich man), or a neutral
      context (e.g., her dad lived on the other side of town) that activates neither of
      the two models previously suggested. The results corroborated our hypothesis.
      Pragmatics is implicated in the unfolding processing of negation. We found an
      increase in fixations on the target compared to the baseline for negative
      sentences at 800 ms in the neutral context, 600 ms in the inconsistent context,
      and 1450 ms in the consistent context. Thus, when the negated situation has been
      previously introduced via an inconsistent context, negation is facilitated.

PMID- 26207956
TI  - Does training with 3D videos improve decision-making in team invasion sports?
AB  - We examined the effectiveness of video-based decision training in national youth
      handball teams. Extending previous research, we tested in Study 1 whether a three
      dimensional (3D) video training group would outperform a two-dimensional (2D)
      group. In Study 2, a 3D training group was compared to a control group and a
      group trained with a traditional tactic board. In both studies, training duration
      was 6 weeks. Performance was measured in a pre- to post-retention design. The
      tests consisted of a decision-making task measuring quality of decisions (first
      and best option) and decision time (time for first and best option). The results
      of Study 1 showed learning effects and revealed that the 3D video group made
      faster first-option choices than the 2D group, but differences in the quality of
      options were not pronounced. The results of Study 2 revealed learning effects for
      both training groups compared to the control group, and faster choices in the 3D
      group compared to both other groups. Together, the results show that 3D video
      training is the most useful tool for improving choices in handball, but only in
      reference to decision time and not decision quality. We discuss the usefulness of
      a 3D video tool for training of decision-making skills outside the laboratory or
      gym. 

PMID- 26207957
TI  - Epigallocatechin-3-gallate enhances clearance of phosphorylated tau in primary
      neurons.
AB  - OBJECTIVES: Alzheimer's disease (AD) is a neurodegenerative disorder
      characterized by intracellular accumulations of phosphorylated forms of the
      microtubule binding protein tau. This study aimed to explore a novel mechanism
      for enhancing the clearance of these pathological tau species using the green tea
      flavonoid epigallocatechin-3-gallate (EGCG). EGCG is a potent antioxidant and an
      activator of the Nrf2 transcriptional pathway. Nrf2 activators including EGCG
      have shown promise in mitigating amyloid pathology in vitro and in vivo. This
      study assessed whether EGCG could also alter tau clearance. METHODS: Rat primary
      cortical neuron cultures were treated on day in vitro 8 with EGCG and analyzed
      for changes in gene and protein expression using luciferase assay, q-PCR, and
      western blotting. RESULTS: EGCG treatment led to a significant decrease in the
      protein levels of three AD-relevant phospho-tau epitopes. Unexpectedly, EGCG does
      not appear to be facilitating this effect through the Nrf2 pathway or by
      increasing autophagy in general. However, EGCG did significantly increase mRNA
      expression of the key autophagy adaptor proteins NDP52 and p62. DISCUSSION: In
      this study, we show that EGCG enhances the clearance of AD-relevant
      phosphorylated tau species in primary neurons. Interestingly, this result appears
      to be independent of both Nrf2 activation and enhanced autophagy - two previously
      reported mechanisms of phytochemical-induced tau clearance. EGCG did
      significantly increase expression of two autophagy adaptor proteins. Taken
      together, these results demonstrate that EGCG has the ability to increase the
      clearance of phosphorylated tau species in a highly specific manner, likely
      through increasing adaptor protein expression.

PMID- 26207958
TI  - Pregnancy outcomes in women with chronic endometritis and recurrent pregnancy
      loss.
AB  - OBJECTIVE: To evaluate the prevalence of chronic endometritis (CE) in women with
      recurrent pregnancy loss (RPL) and compare pregnancy outcomes in women with and
      without CE. DESIGN: Case-control observational study. SETTING: Academic fertility
      practice. PATIENT(S): Women with two or more pregnancy losses. INTERVENTION(S):
      Hematoxylin and eosin (H & E) staining was performed on all endometrial biopsies
      and plasma cells were identified by morphology. Immunohistochemical (IHC)
      staining for CD138 was later applied to all tissue samples. Charts were reviewed
      to evaluate the outcome of the next clinical intrauterine pregnancy. MAIN OUTCOME
      MEASURE(S): Miscarriage rate and live birth rate. RESULT(S): A total of 107 women
      met inclusion criteria. The use of CD138 IHC staining resulted in a significantly
      higher prevalence of CE compared with the use of H & E staining and morphological
      assessment alone (56% [60/107] vs. 13% [14/107]). The 51 women with untreated CE
      were compared with the 45 women without CE by CD138 staining. Among those women
      with a subsequent pregnancy, the live birth rate in the next clinical
      intrauterine pregnancy after endometrial evaluation was 67.6% (23/34) in women
      with untreated CE and 87.1% (27/31) in women without CE. Age, body mass index
      (BMI), results of RPL evaluation, and number of prior losses were not
      significantly different between the two groups. CONCLUSION(S): CD138 IHC staining
      of endometrial biopsies in women with RPL provides increased sensitivity when
      screening for CE compared with H & E staining and morphological assessment alone.
      Untreated CE may contribute to poor pregnancy outcomes and deserves further
      investigation in a larger cohort.

PMID- 26207959
TI  - MicroRNA: a step beyond bulk seminal parameters?

PMID- 26207960
TI  - Live delivery outcome after tubal sterilization reversal: a population-based
      study.
AB  - OBJECTIVE: To determine the cumulative incidence of live delivery in women who
      underwent reversal of tubal sterilization. DESIGN: Population-based retrospective
      cohort study. SETTING: Hospitals in Western Australia. PATIENT(S): All women aged
      20-44 years, with a history of hospital admission for tubal sterilization, who
      subsequently underwent reversal of sterilization during the period 1985 to 2009
      in Western Australia (n = 1,898). INTERVENTION(S): Data regarding reversal of
      sterilization and prior tubal sterilization were extracted from routinely
      collected administrative hospital separation records, until commencement of IVF
      treatment. MAIN OUTCOME MEASURE(S): First live-delivery rates. RESULT(S): There
      were 969 first live deliveries observed during the study period. The overall
      cumulative live-delivery rate was 20% (95% confidence interval [CI] 18-23) within
      the first year after reversal, 40% (95% CI 38-42) at 2 years, 51% (95% CI 48-53)
      at 5 years, and 52% (95% CI 50-55) at 10 years. The 5-year cumulative live
      delivery rate was significantly lower in women who were aged 40-44 years (26%)
      compared with younger women (aged 20-29, 30-34, and 35-39 years) (50%, 56%, and
      51%, respectively). CONCLUSION(S): Women undergoing reversal of sterilization
      before they reach age 40 years have at least a 50% chance of delivering a live
      baby within the next 5 years. Up to that age, there is no significant difference
      in live deliveries. The live-delivery rate halves after the age of 40 years.

PMID- 26207961
TI  - The time to prevent mendelian genetic diseases from donated or own gametes has
      come.

PMID- 26207962
TI  - Single human sperm cryopreservation method using hollow-core agarose capsules.
AB  - OBJECTIVE: To develop an efficient cryopreservation method using a single sperm.
      DESIGN: Experimental study. SETTING: Laboratory of a private institute.
      PATIENT(S): A fertile donor. INTERVENTION(S): We produced hollow-core capsules
      with agarose walls. A single human sperm was injected into each capsule as per
      the conventional intracytoplasmic sperm injection (ICSI) method. The capsules
      that contained the spermatozoa were cryopreserved on polycarbonate or nylon mesh
      sheets using nitrogen vapor. Before their use, the capsules were thawed and
      recovered. The motile spermatozoa in the capsules were counted. MAIN OUTCOME
      MEASURE(S): The recovery rates of the agarose capsules and the spermatozoa in
      these capsules after thawing and the mortality and survival rates of the
      spermatozoa. RESULT(S): The recovery rates of the capsules were 91.5% (75/82)
      using polycarbonate sheets (PS) and 98.3% (59/60) using mesh sheets (MS) after
      thawing. The recovered capsules were not at all damaged. The recovery rates of
      the spermatozoa were 91.5% (75/82) using PS and 96.7% (58/60) using MS. Sperm
      motility rates were 85.3% (64/75) and 82.8% (48/58), whereas the survival rates
      of the immotile spermatozoa by the hypoosmotic swelling test were 81.8% (9/11)
      and 50.0% (5/10); furthermore, the total survival rates of the spermatozoa were
      97.3% (73/75) and 91.4% (53/58) using PS and MS, respectively. There was no
      significant difference between the results obtained using PS and MS.
      CONCLUSION(S): A cryopreservation method for a single sperm using an agarose
      capsule has been developed. The method is expected to be useful in ICSI treatment
      in patients with few spermatozoa.

PMID- 26207964
TI  - Noninvasive assessment of intracranial pressure in dogs by use of biomechanical
      response behavior, diagnostic imaging, and finite element analysis.
AB  - OBJECTIVE :To develop a novel method for use of diagnostic imaging, finite
      element analysis (FEA), and simulated biomechanical response behavior of brain
      tissue in noninvasive assessment and estimation of intracranial pressure (ICP) of
      dogs. SAMPLE: MRI data for 5 dogs. PROCEDURES: MRI data for 5 dogs (1 with a
      geometrically normal brain that had no detectable signs of injury or disease and
      4 with various degrees of geometric abnormalities) were obtained from a digital
      imaging archiving and communication system database. Patient-specific 3-D models
      composed of exact brain geometries were constructed from MRI images. Finite
      element analysis was used to simulate and observe patterns of nonlinear biphasic
      biomechanical response behavior of geometrically normal and abnormal canine
      brains at various levels of decreasing cerebral perfusion pressure and increasing
      ICP. RESULTS: Changes in biomechanical response behavior were detected with FEA
      for decreasing cerebral perfusion pressure and increasing ICP. Abnormalities in
      brain geometry led to observable changes in deformation and biomechanical
      response behavior for increased ICP, compared with results for geometrically
      normal brains. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, patient
      specific critical ICP was identified, which could be useful as a method to
      predict the onset of brain herniation. Results indicated that it was feasible to
      apply FEA to brain geometry obtained from MRI data of clinical patients and to
      use biomechanical response behavior resulting from increased ICP as a diagnostic
      and prognostic method to noninvasively assess or classify levels of brain injury
      in clinical veterinary settings.

PMID- 26207965
TI  - Relationship between serum biomarkers of cartilage and bone metabolism and joint
      injury in young Thoroughbred racehorses in training.
AB  - OBJECTIVE: To compare serum concentrations of biomarkers of cartilage and bone
      metabolism between racehorses with a carpal or metacarpophalangeal or
      metatarsophalangeal (ie, fetlock) joint injury and matched uninjured control
      horses, determine changes in biomarker concentrations following joint injury, and
      establish the biomarkers' diagnostic test performance. ANIMALS: 50 Thoroughbred
      racehorses with a carpal or fetlock joint injury and 50 matched uninjured horses
      (control horses). PROCEDURES: Serum concentrations of 2 cartilage synthesis
      biomarkers (carboxy-terminal propeptide of type II collagen [CPII] and
      chondroitin sulfate epitope 846 [CS846]), 2 cartilage degradation biomarkers
      (neoepitope generated by collagenase cleavage of type II collagen [C2C] and cross
      linked carboxy-terminal telopeptide fragments of type II collagen [CTX-II]), and
      serum activity of a bone formation marker (bone-specific alkaline phosphatase
      [BAP]) were measured around the time of injury diagnosis and monthly thereafter
      for as long as possible. RESULTS: Injured horses as a group and horses
      specifically with fetlock joint injuries had significantly lower serum CPII
      concentrations and significantly higher serum BAP activities than matched control
      horses. Concentrations of CTX-II were decreased between 2 and 4 months following
      joint injury. Measurement of CPII concentration at baseline could distinguish
      between injured horses and control horses with a sensitivity of 82% and
      specificity of 50%. CONCLUSIONS AND CLINICAL RELEVANCE: Although significant
      differences in specific biomarker concentrations between horses with carpal and
      fetlock joint injuries and matched control horses were identified, there was no
      convincing evidence of the suitability of these biomarkers as diagnostic or
      prognostic tools in a clinical setting.

PMID- 26207966
TI  - Electrocardiogram reference intervals for clinically normal wild-born chimpanzees
      (Pan troglodytes).
AB  - OBJECTIVE: To generate reference intervals for ECG variables in clinically normal
      chimpanzees (Pan troglodytes). ANIMALS: 100 clinically normal (51 young [< 10
      years old] and 49 adult [>= 10 years old]) wild-born chimpanzees. PROCEDURES:
      Electrocardiograms collected between 2009 and 2013 at the Tchimpounga Chimpanzee
      Rehabilitation Centre were assessed to determine heart rate, PR interval, QRS
      duration, QT interval, QRS axis, P axis, and T axis. Electrocardiographic
      characteristics for left ventricular hypertrophy (LVH) and morphology of the ST
      segment, T wave, and QRS complex were identified. Reference intervals for young
      and old animals were calculated as mean +/- 1.96*SD for normally distributed data
      and as 5th to 95th percentiles for data not normally distributed. Differences
      between age groups were assessed by use of unpaired Student t tests. RESULTS
      Reference intervals were generated for young and adult wild-born chimpanzees.
      Most animals had sinus rhythm with small or normal P wave morphology; 24 of 51
      (47%) young chimpanzees and 30 of 49 (61%) adult chimpanzees had evidence of LVH
      as determined on the basis of criteria for humans. CONCLUSIONS AND CLINICAL
      RELEVANCE: Cardiac disease has been implicated as the major cause of death in
      captive chimpanzees. Species-specific ECG reference intervals for chimpanzees may
      aid in the diagnosis and treatment of animals with, or at risk of developing,
      heart disease. Chimpanzees with ECG characteristics outside of these intervals
      should be considered for follow-up assessment and regular cardiac monitoring.

PMID- 26207967
TI  - Dynamic computed tomographic determination of scan delay for use in performing
      cardiac angiography in clinically normal dogs.
AB  - OBJECTIVE: To determine the scan delay for use in performing cardiac CT
      angiography in dogs. ANIMALS: 4 clinically normal adult Beagles. PROCEDURES: In a
      crossover study, 12 formulations of iohexol solutions differing in iodine dose
      (300, 400, and 800 mg/kg) and concentration (undiluted and diluted 1:1, 1:2, and
      1:3 with saline [0.9% NaCl] solution) were administered IV to each dog. Dynamic
      CT angiography was performed to evaluate enhancement characteristics of each
      formulation, with the region of interest set over the aorta. Time-attenuation
      curves (TACs) were obtained and analyzed. RESULTS: Peak arc-type TACs were
      obtained after administration of all undiluted formulations. Curve shape changed
      from peak arc type to plateau type as the total volume of the contrast solution
      (ie, dilution) increased. Prolonged peaks characteristic of plateau-type TACs
      suggested that a sufficient period of homogeneous attenuation could be achieved
      for CT scanning with administration of higher iohexol dilutions (1:2 or 1:3)
      containing higher iodine doses (400 or 800 mg/kg). In particular, attenuation
      values for plateau-type TACs remained between 200 and 300 Hounsfield units for >
      16 seconds after the plateau endpoint was reached for 1:2 and 1:3 dilutions
      containing an iodine dose of 800 mg/kg. Scan delays of 13 to 17 seconds were
      computed for those 2 formulations. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that for clinically normal dogs, a scan delay of 13 to 17 seconds could
      be used to perform cardiac CT angiography with iohexol solutions containing an
      iodine dose of 800 mg/kg at dilutions of 1:2 or 1:3.

PMID- 26207968
TI  - Effects of various cardiovascular drugs on indices obtained with two-dimensional
      speckle tracking echocardiography of the left atrium and time-left atrial area
      curve analysis in healthy dogs.
AB  - OBJECTIVE: To evaluate the effects of dobutamine, esmolol, milrinone, and
      phenylephrine on left atrial phasic function of healthy dogs. ANIMALS: 9 healthy
      Beagles. PROCEDURES: Following sedation with propofol on each of 4 experimental
      days, dogs were administered a constant rate infusion of dobutamine (5
      MUg/kg/min), esmolol (500 MUg/kg/min), milrinone (25 MUg/kg, IV bolus, followed
      by 0.5 MUg/kg/min), or phenylephrine (2 MUg/kg/min). There was at least a 14-day
      interval between experimental days. Each drug was administered to 6 dogs.
      Conventional and 2-D speckle tracking echocardiography were performed before
      (baseline) and after administration of the cardiovascular drug, and time-left
      atrial area curves were derived to calculate indices for left atrial reservoir,
      conduit, and booster pump functions (left atrial phasic function) and left
      ventricular contractility and lusitropy. RESULTS: Compared with baseline values,
      indices for left atrial reservoir and booster pump functions and left ventricular
      contractility and lusitropy were significantly increased following dobutamine
      administration; indices for left atrial phasic function and left ventricular
      lusitropy were changed insignificantly, and indices for left ventricular
      contractility were significantly impaired following esmolol administration;
      indices for left atrial phasic function and left ventricular relaxation were
      changed insignificantly, and indices for left ventricular systolic function were
      significantly augmented following milrinone administration; and indices for left
      atrial phasic function and left ventricular lusitropy were changed
      insignificantly, and indices of ventricular contractility were significantly
      impaired following phenylephrine administration. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results indicated that, following administration of dobutamine,
      esmolol, milrinone, or phenylephrine to healthy dogs, left atrial phasic function
      indices were fairly stable and did not parallel changes in left ventricular
      function indices.

PMID- 26207969
TI  - Effect of dietary nonphytate phosphorus content on ileal lymphocyte
      subpopulations and cytokine expression in the cecal tonsils and spleen of laying
      hens that were or were not orally inoculated with Salmonella Typhimurium.
AB  - OBJECTIVE: To evaluate the effects of dietary nonphytate phosphorus (NPP) content
      on ileal lymphocyte subpopulations and cytokine expression in the cecal tonsils
      and spleen of hens that were or were not inoculated with Salmonella Typhimurium.
      ANIMALS: 64 Salmonella-free hens. PROCEDURES: Hens were fed a diet with 0.22%
      (control; n = 32) or 0.42% (high-P; 32) NPP for 6 weeks and then orally
      inoculated with S Typhimurium (5 * 10(7) CFUs) or PBSS. Tissues were obtained
      from 8 S Typhimurium-inoculated and 8 PBSS-inoculated hens from each group at 2
      and 7 days postinoculation (DPI). Percentages of ileal CD4+ and CD8+ lymphocytes
      were determined by flow cytometry. Cytokine mRNA expression was determined by
      quantitative real-time PCR assays. RESULTS: For S Typhimurium-inoculated hens,
      plasma parathyroid hormone concentration was significantly increased and 1,25
      dihydroxyvitamin D3 concentration was decreased in hens fed the high-P diet,
      compared with values in hens fed the control diet. Salmonella Typhimurium
      inoculation caused an increase in the percentage of ileal CD8+ lymphocytes and
      the expression of interleukin (IL)-1beta, IL-6, IL-8, interferon-gamma, IL-12,
      and IL-18 in the cecal tonsils and spleen and a decrease in the expression of IL
      4 and IL-10 in the cecal tonsils. Hens fed the high-P diet had significantly
      increased splenic expression of interferon-gamma at 2 DPI and IL-1beta, IL-6, IL
      12, and IL-18 at 7 DPI, compared with hens fed the control diet. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested there was a T-helper 1 cytokine reaction in
      the cecal tonsils and spleen of S Typhimurium-inoculated hens, and dietary NPP
      content altered calcium regulation hormone concentrations and affected splenic
      cytokine expression.

PMID- 26207970
TI  - Pharmacokinetic evaluation of immediate- and extended-release formulations of
      levetiracetam in dogs.
AB  - OBJECTIVE: To compare the pharmacokinetics of various formulations of
      levetiracetam after oral administration of a single dose to healthy dogs.
      ANIMALS: 6 neurologically normal mixed-breed dogs. PROCEDURES: A crossover study
      design was used. Blood samples for serum harvest were collected from each dog
      before and at various points after oral administration of one 500-mg tablet of
      each of 2 generic extended-release (ER) formulations, 1 brand-name ER
      formulation, or 1 brand-name immediate-release (IR) formulation of levetiracetam.
      Serum samples were analyzed to determine pharmacokinetic properties of each
      formulation by means of ultra-high-performance liquid chromatography with tandem
      mass spectrometry. RESULTS: No dogs had clinically important adverse effects for
      any formulation of levetiracetam. All ER formulations had a significantly lower
      maximum serum drug concentration and longer time to achieve that concentration
      than did the IR formulation. Half-lives and elimination rate constants did not
      differ significantly among formulations. Values for area under the drug
      concentration-versus-time curve did not differ significantly between ER
      formulations and the IR formulation; however, 1 generic ER formulation had a
      significantly lower area under the curve than did other ER formulations.
      CONCLUSIONS AND CLINICAL RELEVANCE: All ER formulations of levetiracetam had
      similar pharmacokinetic properties in healthy dogs, with some exceptions. Studies
      will be needed to evaluate the clinical efficacy of the various formulations;
      however, findings suggested that twice-daily administration of ER formulations
      may be efficacious in the treatment of seizures in dogs.

PMID- 26207971
TI  - Relationship between intracranial pressure as measured by an epidural
      intracranial pressure monitoring system and optic nerve sheath diameter in
      healthy dogs.
AB  - OBJECTIVE: To evaluate the association between ultrasonographically measured
      optic nerve sheath diameter (ONSD) and acute increases in intracranial pressure
      (ICP) as measured by an epidural intracranial pressure monitoring system (EICPMS)
      in healthy dogs. ANIMALS: 6 young healthy dogs. PROCEDURES: An EICPMS connected
      to a pressure monitor was used to generate a continuous pressure waveform in each
      anesthetized dog. A 22-gauge IV catheter was inserted into the brain parenchyma
      through the contralateral parietal bone, and 0.5 to 2.0 mL of anticoagulated
      autologous blood was injected at predetermined intervals. At baseline
      (immediately after EICPMS placement) and following each injection, the ICP as
      indicated by EICPMS was recorded, and 3 ultrasonographic images of the optic
      nerve sheath of each eye were obtained. The ONSD was measured at maximum diameter
      and at 5 mm caudal to the optic disk. RESULTS: In linear models, the maximum ONSD
      was positively associated with increasing ICP. Specifically, the rate of maximum
      ONSD increase was greater for pressures <= 20 mm Hg above baseline (0.0534 mm/1
      mm Hg ICP increase) than for pressures > 40 mm Hg above baseline (0.0087 mm/1 mm
      Hg ICP increase). The relationship of ICP to maximum ONSD was slightly nonlinear
      and best explained by comparison of fractional polynomial regression models.
      CONCLUSIONS AND CLINICAL RELEVANCE: ICP was positively and nonlinearly associated
      with increasing maximum ONSD, especially when ICP was <= 20 mm Hg above baseline,
      supporting the conclusion that ultrasonographic measurement of maximum ONSD may
      provide a noninvasive monitoring tool for evaluation of ICP in dogs. Further
      research is needed to assess the utility of these measurements in clinical
      patients.

PMID- 26207972
TI  - Pharmacokinetics and pharmacodynamics of the factor Xa inhibitor apixaban after
      oral and intravenous administration to cats.
AB  - OBJECTIVE: To determine pharmacokinetic and pharmacodynamic properties of the
      novel factor Xa inhibitor apixaban in clinically normal cats. ANIMALS: 5 purpose
      bred domestic shorthair cats. PROCEDURES: A single dose of apixaban (0.2 mg/kg,
      PO) was administered to each cat (time 0), and blood samples were obtained at 0,
      15, 30, 45, 60, 120, 240, 360, 480, and 1,440 minutes. After a 1-week washout
      period, another dose of apixaban (0.2 mg/kg, IV) was administered to each cat,
      and blood samples were obtained at 0, 5, 10, 15, 30, 45, 60, 120, 240, 360, 480,
      and 1,440 minutes. Apixaban concentrations in plasma were measured via liquid
      chromatography-tandem mass spectrometry. Pharmacodynamic effects of apixaban were
      determined with a commercial assay for factor * activity, which measures
      endogenous factor Xa activity chromogenically. RESULTS: Factor Xa was inhibited
      as a function of time after a single dose of apixaban administered orally or IV,
      and a direct inverse correlation with the plasma apixaban concentration was
      detected. Pharmacokinetic analysis revealed moderate clearance, short half-life,
      and high bioavailability for apixaban. A 2-compartment model was fit to the IV
      pharmacokinetic data; compartmental modeling could not be used to adequately
      describe the oral data because of substantial interindividual variability.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results inticated that apixaban was an
      effective inhibitor of factor Xa in cats. Further studies will be needed to
      determine pharmacokinetics and pharmacodynamics after multidose administration,
      effects of cardiac disease on pharmacokinetics and pharmacodynamics, dosing
      recommendations, and efficacy of apixaban for use in the treatment and prevention
      of thromboembolic disease in cats.

PMID- 26207973
TI  - Discrimination of healthy versus sick steers by means of continuous remote
      monitoring of animal activity.
AB  - OBJECTIVE: To test a unique electronic ear tag designed to collect movement data
      to determine whether physical activity of sick steers differed from that of
      healthy steers. ANIMALS: 206 steers. PROCEDURES: Physical activity in 2 groups of
      steers during November and December of 2010 (101 steers; the tag of 1 steer
      failed, and thus that steer was removed from the study, which resulted in data
      for 100 steers) and 2011 (105 steers) was monitored with an electronic ear tag
      device with an on-board triple-axis accelerometer. The accelerometer recorded
      motion in all 3 axes in the form of counts per minute. A radio-frequency
      transmitter on the ear tag delivered serial packets of motion data to a local
      server. An algorithm was developed to analyze the activity data to determine
      whether this technique could be used to assess health status with high accuracy.
      RESULTS: Steers that became sick had significantly fewer activity counts (approx
      25% fewer), compared with the activity counts of steers that remained healthy the
      entire time. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, automated
      detection of health status in growing cattle was feasible through remote
      monitoring of animal activity. Early identification of sick animals should lead
      to improved health outcomes, increased marketability, and improved animal well
      being and help to minimize the use of antimicrobials that could contribute to
      resistant bacteria.

PMID- 26207974
TI  - Two new lignans from twigs of Aglaia odorata.
AB  - HPLC-guided separation of twigs of Aglaia odorata led to the isolation of eight
      lignans, including two new ones, 3'-methoxy-N-demethylrocaglamide (1) and 4'-O
      demethyl-deacetylaglaxiflorin A (2). Compound 1 showed excellent cytotoxicity
      against three human cancer cell lines, HeLa, SGC-7901 gastric cancer, and A-549
      lung cancer with the values of 0.32, 0.12, and 0.25 MUM, respectively. 

PMID- 26207975
TI  - Effects of Weight-Bearing Biofeedback Training on Functional Movement Patterns
      Following Total Knee Arthroplasty: A Randomized Controlled Trial.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To examine the effects of
      weight-bearing biofeedback training on weight-bearing symmetry and functional
      joint moments following unilateral total knee arthroplasty. BACKGROUND:
      Individuals after unilateral total knee arthroplasty place more weight on the
      nonsurgical limb compared to the surgical limb during function. It is unknown
      whether targeted intervention can improve function in the surgical limb and
      resolve altered movement patterns. METHODS: Twenty-six patients were randomly
      assigned to 2 groups (reload or control). The reload group had a standard-of-care
      rehabilitation augmented with weight-bearing biofeedback training, and the
      control group had a dose-matched standard-of-care rehabilitation. Lower-limb
      weight-bearing ratios were measured preoperatively and 6 and 26 weeks after total
      knee arthroplasty during a 5-time sit-to-stand test (FTSST) and walking.
      Secondary outcomes were FTSST time, walking speed, and lower-limb joint moments
      during the FTSST and walking. RESULTS: No between-group differences were found in
      weight-bearing ratios. Five-time sit-to-stand test time improved in the reload
      group compared to the control group at 6 (P = .021) and 26 weeks (P = .021).
      There were no between-group differences in knee extension moment during the
      FTSST. Surgical-limb knee extension moments during walking increased from
      baseline to 26 weeks in the reload group and decreased in the control group (P =
      .008). CONCLUSION: Weight-bearing biofeedback training had no effect on
      functional weight-bearing symmetry or knee extension moments during the FTSST.
      However, the biofeedback training resulted in increases of knee extension moments
      during gait and improved FTSST times. Trial registered at ClinicalTrials.gov
      (NCT01333189). Level of Evidence Therapy, level 2b.

PMID- 26207976
TI  - Synthesis and characterization of biomatrixed-gold nanoparticles by the mushroom
      Flammulina velutipes and its heterogeneous catalytic potential.
AB  - Sustainable and greener synthesis of intracellular gold nanoparticles using
      mushroom Flammulina velutipes is reported. Incubation of a mushroom in
      chloroaurate solution resulted in the synthesis and immobilization of stable gold
      nanoparticles inside the mushroom mycelia. Transmission electron microscopic
      (TEM) analysis revealed the presence of gold nanoparticles (?20nm) inside the
      mycelia, primarily on the inner surface of the cell membrane. Inductively coupled
      plasma-optical emission spectrometry (ICP-OES) revealed that the accumulated gold
      concentration ranged from 64.4 to 330.5mgkg(-1) dry weight (DW) in the mushroom
      mycelia. The reduction of Au(3+) ions to Au(0) and stabilization of gold
      nanoparticles occurred within 1h, and the formation of fcc crystalline gold
      nanoparticles was confirmed by X-ray diffraction (XRD) analysis. This facile
      intracellular synthesis of gold nanoparticles by a mushroom without using any
      toxic chemicals or technologically expensive processes is used as a heterogeneous
      catalyst in the reduction of organic pollutants methylene blue (MB) and 4
      nitrophenol (4NP). The reduction reaction follows pseudo-first order kinetics
      with a reaction rate constant of 0.0529min(-1) and 0.1236min(-1) for MB and 4NP,
      respectively. This biological process of biomatrixing of metal nanoparticles for
      heterogeneous catalytic reactions is simple, nontoxic, environmentally benign,
      and economically viable compared to the chemical synthetic routes. 

PMID- 26207977
TI  - Transport Properties of Multivalent Cations in Nafion-117 Membrane with Mixed
      Ionic Composition.
AB  - The transport characteristics of multivalent cations like Ba(2+) and Eu(3+) have
      been studied in bi-ionic form of the Nafion-117 membrane. The membranes have been
      prepared by loading different proportions of H(+)-Ba(2+)/Mg(2+)-Ba(2+)/Ba(2+)
      Eu(3+)/H(+)-Eu(3+)/Na(+)-Eu(3+). The cationic compositions of the membranes have
      been determined from the measured ion exchange isotherms. Results show that the
      self-diffusion coefficient of Ba(2+) (D(Ba)) in H-Ba/Mg-Ba systems as well as the
      self-diffusion coefficient of Eu(3+) (D(Eu)) in H-Eu/Na-Eu systems are strongly
      dependent on the membrane ionic compositions and decreased continuously with
      increasing concentration of the highly hydrated ions (H(+)/Na(+)/Mg(2+)) in the
      membrane. Increase in the proportion of H(+)/Na(+)/Mg(2+) ions in the membrane
      increases the effective charge on the membrane matrix. This causes stronger
      electrostatic interaction of the less hydrated multivalent ions (Ba(2+)/Eu(3+))
      with the membrane matrix charges, which ultimately results in their slower self
      diffusion coefficients. The higher the valence, the stronger the electrostatic
      interaction is with the fixed ionic charges; hence, in general, D(Eu) is affected
      more as compared to D(Ba). On the basis of the free-volume theory for polymers,
      the effective interaction potential (Phi) of the Ba(2+) with the fixed ionic
      sites in the membrane has been calculated and found to be on the order of
      approximately millivolts. The higher the proportion of hydrated ion in the
      membrane, the higher the Phi is and the stronger the ion pair formation is with
      the fixed ionic sites in the membrane. However, in the Ba-Eu system, as the
      electrostatic interactions of the two ions with the membrane matrix are close,
      D(Ba) and D(Eu) are independent of the membrane ionic composition. The ionic
      composition dependence of D(Ba) in the H-Ba system is reflected in the transport
      rate of Ba(2+), showing the importance of such measurements in understanding the
      transport characteristics of the membrane.

PMID- 26207978
TI  - Loss of Dopamine Transporter Binding and Clinical Symptoms in Dementia With Lewy
      Bodies.
AB  - BACKGROUND: Little is known about the underlying mechanisms of clinical symptoms
      in dementia with Lewy bodies. The aim of this study was to explore the
      association between loss of striatal dopamine transporter binding and symptoms in
      dementia with Lewy bodies. METHODS: Thirty-five patients with dementia with Lewy
      bodies underwent single-photon emission computerized tomography brain imaging
      with N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane
      ([(123) I]FP-CIT). Associations between striatal binding ratios and motor
      (UPDRS), psychiatric (Neuropsychiatric Inventory; [NPI]), and cognitive (Mini
      Mental State Examination [MMSE] and neuropsychological tests) symptoms were
      assessed by linear regression analysis. RESULTS: The explorative analysis showed
      that the motor UPDRS was negatively associated with putamen dopamine transporter
      binding, whereas no association with striatal dopamine transporter binding was
      found for total NPI, hallucinations, apathy, depression, anxiety, and MMSE
      scores. However, in post-hoc analysis, executive impairment was positively
      associated with dopamine transporter loss after adjustment of age and gender.
      CONCLUSIONS: Dopamine deficiency in patients with dementia with Lewy bodies was
      associated with severity of motor symptoms, but did not correlate significantly
      with ratings of neurobehavioral disturbances or overall cognition.

PMID- 26207979
TI  - Vibrational Imaging of Glucose Uptake Activity in Live Cells and Tissues by
      Stimulated Raman Scattering.
AB  - Glucose is a ubiquitous energy source for most living organisms. Its uptake
      activity closely reflects cellular metabolic demand in various physiopathological
      conditions. Extensive efforts have been made to specifically image glucose
      uptake, such as with positron emission tomography, magnetic resonance imaging,
      and fluorescence microscopy, but all have limitations. A new platform to
      visualize glucose uptake activity in live cells and tissues is presented that
      involves performing stimulated Raman scattering on a novel glucose analogue
      labeled with a small alkyne moiety. Cancer cells with differing metabolic
      activities can be distinguished. Heterogeneous uptake patterns are observed with
      clear cell-cell variations in tumor xenograft tissues, neuronal culture, and
      mouse brain tissues. By offering the distinct advantage of optical resolution but
      without the undesirable influence of fluorophores, this method will facilitate
      the study of energy demands of living systems with subcellular resolution. 

PMID- 26207980
TI  - Fetal growth restriction and intra-uterine growth restriction: guidelines for
      clinical practice from the French College of Gynaecologists and Obstetricians.
AB  - Small for gestational age (SGA) is defined by weight (in utero estimated fetal
      weight or birth weight) below the 10th percentile (professional consensus).
      Severe SGA is SGA below the third percentile (professional consensus). Fetal
      growth restriction (FGR) or intra-uterine growth restriction (IUGR) usually
      correspond with SGA associated with evidence indicating abnormal growth (with or
      without abnormal uterine and/or umbilical Doppler): arrest of growth or a shift
      in its rate measured longitudinally (at least two measurements, 3 weeks apart)
      (professional consensus). More rarely, they may correspond with inadequate
      growth, with weight near the 10th percentile without being SGA (LE2). Birthweight
      curves are not appropriate for the identification of SGA at early gestational
      ages because of the disorders associated with preterm delivery. In utero curves
      represent physiological growth more reliably (LE2). In diagnostic (or reference)
      ultrasound, the use of growth curves adjusted for maternal height and weight,
      parity and fetal sex is recommended (professional consensus). In screening, the
      use of adjusted curves must be assessed in pilot regions to determine the
      schedule for their subsequent introduction at national level. This choice is
      based on evidence of feasibility and the absence of any proven benefits for
      individualized curves for perinatal health in the general population
      (professional consensus). Children born with FGR or SGA have a higher risk of
      minor cognitive deficits, school problems and metabolic syndrome in adulthood.
      The role of preterm delivery in these complications is linked. The measurement of
      fundal height remains relevant to screening after 22 weeks of gestation (Grade
      C). The biometric ultrasound indicators recommended are: head circumference (HC),
      abdominal circumference (AC) and femur length (FL) (professional consensus). They
      allow calculation of estimated fetal weight (EFW), which, with AC, is the most
      relevant indicator for screening. Hadlock's EFW formula with three indicators
      (HC, AC and FL) should ideally be used (Grade B). The ultrasound report must
      specify the percentile of the EFW (Grade C). Verification of the date of
      conception is essential. It is based on the crown-rump length between 11 and 14
      weeks of gestation (Grade A). The HC, AC and FL measurements must be related to
      the appropriate reference curves (professional consensus); those modelled from
      College Francais d'Echographie Fetale data are recommended because they are
      multicentere French curves (professional consensus). Whether or not a work-up
      should be performed and its content depend on the context (gestational age,
      severity of biometric abnormalities, other ultrasound data, parents' wishes,
      etc.) (professional consensus). Such a work-up only makes sense if it might
      modify pregnancy management and, in particular, if it has the potential to reduce
      perinatal and long-term morbidity and mortality (professional consensus). The use
      of umbilical artery Doppler velocimetry is associated with better newborn health
      status in populations at risk, especially in those with FGR (Grade A). This
      Doppler examination must be the first-line tool for surveillance of fetuses with
      SGA and FGR (professional consensus). A course of corticosteroids is recommended
      for women with an FGR fetus, and for whom delivery before 34 weeks of gestation
      is envisaged (Grade C). Magnesium sulphate should be prescribed for preterm
      deliveries before 32-33 weeks of gestation (Grade A). The same management should
      apply for preterm FGR deliveries (Grade C). In cases of FGR, fetal growth must be
      monitored at intervals of no less than 2 weeks, and ideally 3 weeks (professional
      consensus). Referral to a Level IIb or III maternity ward must be proposed in
      cases of EFW <1500g, potential birth before 32-34 weeks of gestation (absent or
      reversed umbilical end-diastolic flow, abnormal venous Doppler) or a fetal
      disease associated with any of these (professional consensus). Systematic
      caesarean deliveries for FGR are not recommended (Grade C). In cases of vaginal
      delivery, fetal heart rate must be monitored continuously during labour, and any
      delay before intervention must be faster than in low-risk situations
      (professional consensus). Regional anaesthesia is preferred in trials of vaginal
      delivery, as in planned caesareans. Morbidity and mortality are higher in SGA
      newborns than in normal-weight newborns of the same gestational age (LE3). The
      risk of neonatal mortality is two to four times higher in SGA newborns than in
      non-SGA preterm and full-term infants (LE2). Initial management of an SGA newborn
      includes combatting hypothermia by maintaining the heat chain (survival blanket),
      ventilation with a pressure-controlled insufflator, if necessary, and close
      monitoring of capillary blood glucose (professional consensus). Testing for
      antiphospholipids (anticardiolipin, circulating anticoagulant, anti-beta2-GP1) is
      recommended in women with previous severe FGR (below third percentile) that led
      to birth before 34 weeks of gestation (professional consensus). It is recommended
      that aspirin should be prescribed to women with a history of pre-eclampsia before
      34 weeks of gestation, and/or FGR below the fifth percentile with a probable
      vascular origin (professional consensus). Aspirin must be taken in the evening or
      at least 8h after awakening (Grade B), before 16 weeks of gestation, at a dose of
      100-160mg/day (Grade A). 

PMID- 26207982
TI  - Two-Dimensional Porous Carbon: Synthesis and Ion-Transport Properties.
AB  - Their chemical stability, high specific surface area, and electric conductivity
      enable porous carbon materials to be the most commonly used electrode materials
      for electrochemical capacitors (also known as supercapacitors). To further
      increase the energy and power density, engineering of the pore structures with a
      higher electrochemical accessible surface area, faster ion-transport path and a
      more-robust interface with the electrolyte is widely investigated. Compared with
      traditional porous carbons, two-dimensional (2D) porous carbon sheets with an
      interlinked hierarchical porous structure are a good candidate for
      supercapacitors due to their advantages in high aspect ratio for electrode
      packing and electron transport, hierarchical pore structures for ion transport,
      and short ion-transport length. Recent progress on the synthesis of 2D porous
      carbons is reported here, along with the improved electrochemical behavior due to
      enhanced ion transport. Challenges for the controlled preparation of 2D porous
      carbons with desired properties are also discussed; these require precise tuning
      of the hierarchical structure and a clarification of the formation mechanisms. 

PMID- 26207981
TI  - Differential Contribution of TRPA1, TRPV4 and TRPM8 to Colonic Nociception in
      Mice.
AB  - BACKGROUND: Various transient receptor potential (TRP) channels in sensory
      neurons contribute to the transduction of mechanical stimuli in the colon.
      Recently, even the cold-sensing menthol receptor TRPM(melastatin)8 was suggested
      to be involved in murine colonic mechano-nociception. METHODS: To analyze the
      roles of TRPM8, TRPA1 and TRPV4 in distension-induced colonic nociception and
      pain, TRP-deficient mice and selective pharmacological blockers in wild-type mice
      (WT) were used. Visceromotor responses (VMR) to colorectal distension (CRD) in
      vivo were recorded and distension/pressure-induced CGRP release from the isolated
      murine colon ex vivo was measured by EIA. RESULTS: Distension-induced colonic
      CGRP release was markedly reduced in TRPA1-/- and TRPV4-/- mice at 90/150 mmHg
      compared to WT. In TRPM8-deficient mice the reduction was only distinct at 150
      mmHg. Exposure to selective pharmacological antagonists (HC030031, 100 MUM;
      RN1734, 10 MUM; AMTB, 10 MUM) showed corresponding effects. The unselective TRP
      blocker ruthenium red (RR, 10 MUM) was as efficient in inhibiting distension
      induced CGRP release as the unselective antagonists of mechanogated DEG/ENaC
      (amiloride, 100 MUM) and stretch-activated channels (gadolinium, 50 MUM). VMR to
      CRD revealed prominent deficits over the whole pressure range (up to 90 mmHg) in
      TRPA1-/- and TRPV4-/- but not TRPM8-/- mice; the drug effects of the TRP
      antagonists were again highly consistent with the results from mice lacking the
      respective TRP receptor gene. CONCLUSIONS: TRPA1 and TRPV4 mediate colonic
      distension pain and CGRP release and appear to govern a wide and congruent
      dynamic range of distensions. The role of TRPM8 seems to be confined to signaling
      extreme noxious distension, at least in the healthy colon.

PMID- 26207983
TI  - Red Color and Risk-Taking Behavior in Online Environments.
AB  - In many situations red is associated with hazard and danger. As a consequence, it
      was expected that task-irrelevant color cues in online environments would affect
      risk-taking behaviors. This assumption was tested in two web-based experiments.
      The first study (N = 383) demonstrated that in risky choice dilemmas respondents
      preferred the less risky option when the displayed university logo was in red
      (versus gray); but only when both choice alternatives were at least moderately
      risky. The second study (N = 144) replicated these results with a behavioral
      outcome: Respondents showed more cautious behavior in a web-based game when the
      focal stimuli were colored red (versus blue). Together, these findings
      demonstrate that variations in the color design of a computerized environment
      affect risk taking: Red color leads to more conservative choices and behaviors. 

PMID- 26207984
TI  - Anthropogenic Factors Are the Major Cause of Hospital Admission of a Threatened
      Species, the Grey-Headed Flying Fox (Pteropus poliocephalus), in Victoria,
      Australia.
AB  - To determine the reasons for presentation and outcomes of hospitalised grey
      headed flying foxes (Pteropus poliocephalus) in Victoria, Australia, a
      retrospective analysis was performed on 532 records from two wildlife hospitals.
      Cases were categorised based on presenting signs and outcomes determined.
      Anthropogenic factors (63.7%) were a major cause of flying fox admissions with
      entanglement in fruit netting the most significant risk for bats (36.8%). Overall
      the mortality rate for flying fox admissions was 59.3%. This study highlights the
      effects of urbanisation on wild animal populations and a need for continued
      public education in order to reduce morbidity and mortality of wildlife,
      especially threatened species. 

PMID- 26207985
TI  - Reducing Individual Variation for fMRI Studies in Children by Minimizing Template
      Related Errors.
AB  - Spatial normalization is an essential process for group comparisons in functional
      MRI studies. In practice, there is a risk of normalization errors particularly in
      studies involving children, seniors or diseased populations and in regions with
      high individual variation. One way to minimize normalization errors is to create
      a study-specific template based on a large sample size. However, studies with a
      large sample size are not always feasible, particularly for children studies. The
      performance of templates with a small sample size has not been evaluated in fMRI
      studies in children. In the current study, this issue was encountered in a
      working memory task with 29 children in two groups. We compared the performance
      of different templates: a study-specific template created by the experimental
      population, a Chinese children template and the widely used adult MNI template.
      We observed distinct differences in the right orbitofrontal region among the
      three templates in between-group comparisons. The study-specific template and the
      Chinese children template were more sensitive for the detection of between-group
      differences in the orbitofrontal cortex than the MNI template. Proper templates
      could effectively reduce individual variation. Further analysis revealed a
      correlation between the BOLD contrast size and the norm index of the affine
      transformation matrix, i.e., the SFN, which characterizes the difference between
      a template and a native image and differs significantly across subjects. Thereby,
      we proposed and tested another method to reduce individual variation that
      included the SFN as a covariate in group-wise statistics. This correction
      exhibits outstanding performance in enhancing detection power in group-level
      tests. A training effect of abacus-based mental calculation was also
      demonstrated, with significantly elevated activation in the right orbitofrontal
      region that correlated with behavioral response time across subjects in the
      trained group. 

PMID- 26207986
TI  - Improving the Quality of Voluntary Medical Male Circumcision through Use of the
      Continuous Quality Improvement Approach: A Pilot in 30 PEPFAR-Supported Sites in
      Uganda.
AB  - BACKGROUND: Uganda adopted voluntary medical male circumcision (VMMC) (also
      called Safe Male Circumcision in Uganda), as part of its HIV prevention strategy
      in 2010. Since then, the Ministry of Health (MOH) has implemented VMMC mostly
      with support from the United States President's Emergency Plan for AIDS Relief
      (PEPFAR) through its partners. In 2012, two PEPFAR-led external quality
      assessments evaluated compliance of service delivery sites with minimum quality
      standards. Quality gaps were identified, including lack of standardized forms or
      registers, lack of documentation of client consent, poor preparedness for
      emergencies and use of untrained service providers. In response, PEPFAR, through
      a USAID-supported technical assistance project, provided support in quality
      improvement to the MOH and implementing partners to improve quality and safety in
      VMMC services and build capacity of MOH staff to continuously improve VMMC
      service quality. METHODS AND FINDINGS: Sites were supported to identify barriers
      in achieving national standards, identify possible solutions to overcome the
      barriers and carry out improvement plans to test these changes, while collecting
      performance data to objectively measure whether they had bridged gaps. A 53
      indicator quality assessment tool was used by teams as a management tool to
      measure progress; teams also measured client-level indicators through self
      assessment of client records. At baseline (February-March 2013), less than 20
      percent of sites scored in the "good" range (>80%) for supplies and equipment,
      patient counseling and surgical procedure; by November 2013, the proportion of
      sites scoring "good" rose to 67 percent, 93 percent and 90 percent, respectively.
      Significant improvement was noted in post-operative follow-up at 48 hours,
      sexually transmitted infection assessment, informed consent and use of local
      anesthesia but not rate of adverse events. CONCLUSION: Public sector providers
      can be engaged to address the quality of VMMC using a continuous quality
      improvement approach.

PMID- 26207987
TI  - The Biosynthesis of UDP-D-QuiNAc in Bacillus cereus ATCC 14579.
AB  - N-acetylquinovosamine (2-acetamido-2,6-di-deoxy-D-glucose, QuiNAc) is a
      relatively rare amino sugar residue found in glycans of few pathogenic gram
      negative bacteria where it can play a role in infection. However, little is known
      about QuiNAc-related polysaccharides in gram-positive bacteria. In a routine
      screen for bacillus glycan grown at defined medium, it was surprising to identify
      a QuiNAc residue in polysaccharides isolated from this gram-positive bacterium.
      To gain insight into the biosynthesis of these glycans, we report the
      identification of an operon in Bacillus cereus ATCC 14579 that contains two genes
      encoding activities not previously described in gram-positive bacteria. One gene
      encodes a UDP-N-acetylglucosamine C4,6-dehydratase, (abbreviated Pdeg) that
      converts UDP-GlcNAc to UDP-4-keto-4,6-D-deoxy-GlcNAc (UDP-2-acetamido-2,6-dideoxy
      alpha-D-xylo-4-hexulose); and the second encodes a UDP-4-reductase (abbr. Preq)
      that converts UDP-4-keto-4,6-D-deoxy-GlcNAc to UDP-N-acetyl-quinovosamine in the
      presence of NADPH. Biochemical studies established that the sequential Pdeg and
      Preq reaction product is UDP-D-QuiNAc as determined by mass spectrometry and one-
      and two-dimensional NMR experiments. Also, unambiguous evidence for the
      conversions of the dehydratase product, UDP-alpha-D-4-keto-4,6-deoxy-GlcNAc, to
      UDP-alpha-D-QuiNAc was obtained using real-time 1H-NMR spectroscopy and mass
      spectrometry. The two genes overlap by 4 nucleotides and similar operon
      organization and identical gene sequences were also identified in a few other
      Bacillus species suggesting they may have similar roles in the lifecycle of this
      class of bacteria important to human health. Our results provide new information
      about the ability of Bacilli to form UDP-QuiNAc and will provide insight to
      evaluate their role in the biology of Bacillus.

PMID- 26207989
TI  - Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin
      Resistant Ovarian Cancer.
AB  - DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than
      those of normal tissues. TOP1 inhibitors are widely used in treating conventional
      therapy-resistant ovarian cancers. However, patients may develop resistance to
      TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the
      mechanisms associated with the development of camptothecin (CPT) resistance in
      ovarian cancers and identified evodiamine (EVO), a natural product with TOP1
      inhibiting activity that overcomes the resistance. The correlations among TOP1
      levels, cancer staging, and overall survival (OS) were analyzed. The effect of
      EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was
      associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced
      apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased
      significantly in the EVO treatment group compared with the control group (p <
      0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis
      and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be
      developed as an antiproliferative agent for overcoming CPT resistance in ovarian
      cancers. 

PMID- 26207988
TI  - Assessment of mTOR-Dependent Translational Regulation of Interferon Stimulated
      Genes.
AB  - Type-I interferon (IFN)-induced activation of the mammalian target of rapamycin
      (mTOR) signaling pathway has been implicated in translational control of mRNAs
      encoding interferon-stimulated genes (ISGs). However, mTOR-sensitive translatomes
      commonly include mRNAs with a 5' terminal oligopyrimidine tract (TOP), such as
      those encoding ribosomal proteins, but not ISGs. Because these translatomes were
      obtained under conditions when ISG expression is not induced, we examined the
      mTOR-sensitive translatome in human WISH cells stimulated with IFN beta. The mTOR
      inhibitor Torin1 resulted in a repression of global protein synthesis, including
      that of ISG products, and translation of all but 3 ISG mRNAs (TLR3, NT5C3A, and
      RNF19B) was not selectively more sensitive to mTOR inhibition. Detailed studies
      of NT5C3A revealed an IFN-induced change in transcription start site resulting in
      a switch from a non-TOP to a TOP-like transcript variant and mTOR sensitive
      translation. Thus, we show that, in the cell model used, translation of the vast
      majority of ISG mRNAs is not selectively sensitive to mTOR activity and describe
      an uncharacterized mechanism wherein the 5'-UTR of an mRNA is altered in response
      to a cytokine, resulting in a shift from mTOR-insensitive to mTOR-sensitive
      translation. 

PMID- 26207990
TI  - Automated Defect and Correlation Length Analysis of Block Copolymer Thin Film
      Nanopatterns.
AB  - Line patterns produced by lamellae- and cylinder-forming block copolymer (BCP)
      thin films are of widespread interest for their potential to enable nanoscale
      patterning over large areas. In order for such patterning methods to effectively
      integrate with current technologies, the resulting patterns need to have low
      defect densities, and be produced in a short timescale. To understand whether a
      given polymer or annealing method might potentially meet such challenges, it is
      necessary to examine the evolution of defects. Unfortunately, few tools are
      readily available to researchers, particularly those engaged in the synthesis and
      design of new polymeric systems with the potential for patterning, to measure
      defects in such line patterns. To this end, we present an image analysis tool,
      which we have developed and made available, to measure the characteristics of
      such patterns in an automated fashion. Additionally we apply the tool to six
      cylinder-forming polystyrene-block-poly(2-vinylpyridine) polymers thermally
      annealed to explore the relationship between the size of each polymer and
      measured characteristics including line period, line-width, defect density, line
      edge roughness (LER), line-width roughness (LWR), and correlation length.
      Finally, we explore the line-edge roughness, line-width roughness, defect
      density, and correlation length as a function of the image area sampled to
      determine each in a more rigorous fashion. 

PMID- 26207991
TI  - A Sparse Reconstruction Approach for Identifying Gene Regulatory Networks Using
      Steady-State Experiment Data.
AB  - MOTIVATION: Identifying gene regulatory networks (GRNs) which consist of a large
      number of interacting units has become a problem of paramount importance in
      systems biology. Situations exist extensively in which causal interacting
      relationships among these units are required to be reconstructed from measured
      expression data and other a priori information. Though numerous classical methods
      have been developed to unravel the interactions of GRNs, these methods either
      have higher computing complexities or have lower estimation accuracies. Note that
      great similarities exist between identification of genes that directly regulate a
      specific gene and a sparse vector reconstruction, which often relates to the
      determination of the number, location and magnitude of nonzero entries of an
      unknown vector by solving an underdetermined system of linear equations y = Phix.
      Based on these similarities, we propose a novel framework of sparse
      reconstruction to identify the structure of a GRN, so as to increase accuracy of
      causal regulation estimations, as well as to reduce their computational
      complexity. RESULTS: In this paper, a sparse reconstruction framework is proposed
      on basis of steady-state experiment data to identify GRN structure. Different
      from traditional methods, this approach is adopted which is well suitable for a
      large-scale underdetermined problem in inferring a sparse vector. We investigate
      how to combine the noisy steady-state experiment data and a sparse reconstruction
      algorithm to identify causal relationships. Efficiency of this method is tested
      by an artificial linear network, a mitogen-activated protein kinase (MAPK)
      pathway network and the in silico networks of the DREAM challenges. The
      performance of the suggested approach is compared with two state-of-the-art
      algorithms, the widely adopted total least-squares (TLS) method and those
      available results on the DREAM project. Actual results show that, with a lower
      computational cost, the proposed method can significantly enhance estimation
      accuracy and greatly reduce false positive and negative errors. Furthermore,
      numerical calculations demonstrate that the proposed algorithm may have faster
      convergence speed and smaller fluctuation than other methods when either estimate
      error or estimate bias is considered.

PMID- 26207992
TI  - Iridoids and phenylethanoid from Pedicularis kerneri Dalla Torre growing in
      Dolomites, Italy.
AB  - In this study, we report the first phytochemical analysis of polar fraction of
      Pedicularis kerneri Dalla Torre growing in Dolomites, Italy. Several iridoid
      glucosides were isolated, namely aucubin (1), monomelittoside (2),
      plantarenaloside (3), euphroside (4), mussaenosidic acid (5) and 8-epiloganic
      acid (6), showing a composition in accordance with previous study on this genus.
      The studied samples, collected from Dolomites, presented a chemotype already
      recognised in species from North America, characterised by euphroside (4) and
      aucubin (1) as main components, but the main character was the presence of
      monomelittoside (2) never reported in this genus. The identification of
      verbascoside (7), leucosceptoside A (9) and echinacoside (10) complete the
      systematic framing of this species since is ascertained the co-occurrence of
      phenylethanoid glycosides with iridoids in Lamiales species. 

PMID- 26207994
TI  - High definition urethral pressure profilometry: Evaluating a novel microtip
      catheter.
AB  - INTRODUCTION: Urethral pressure profilometry (UPP) is used in the diagnosis of
      stress urinary incontinence (SUI). SUI is a significant medical, social, and
      economic problem, affecting about 12.5% of the population. A novel microtip
      catheter was developed for UPP featuring an inclination sensor and higher angular
      resolution compared to systems in clinical use today. Therewith, the location of
      each measured pressure sample can be determined and the spatial pressure
      distribution inside the urethra reconstructed. In order to assess the performance
      and plausibility of data from the microtip catheter, we compare it to data from a
      double balloon air charged system. MATERIALS AND METHODS: Both catheters are used
      on sedated female minipigs. Data from the microtip catheter are processed through
      a signal reconstruction algorithm, plotted and compared against data from the air
      charged catheter. RESULTS: The microtip catheter delivers results in agreement
      with previous comparisons of microtip and air-charged systems. It additionally
      provides a new level of detail in the reconstructed UPPs which may lead to new
      insights into the sphincter mechanism of minipigs. CONCLUSIONS: The ability of
      air-charged catheters to measure pressure circumferentially is widely considered
      a main advantage over microtip catheters. However, directional pressure readings
      can provide additional information on angular fluctuations in the urethral
      pressure distribution. It is shown that the novel microtip catheter in
      combination with a signal reconstruction algorithm delivers plausible data. It
      offers the opportunity to evaluate urethral structures, especially the sphincter,
      in context of the correct location within the anatomical location of the pelvic
      floor. Neurourol. Urodynam. 35:888-894, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26207993
TI  - Stomatal closure is induced by hydraulic signals and maintained by ABA in drought
      stressed grapevine.
AB  - Water saving under drought stress is assured by stomatal closure driven by active
      (ABA-mediated) and/or passive (hydraulic-mediated) mechanisms. There is currently
      no comprehensive model nor any general consensus about the actual contribution
      and relative importance of each of the above factors in modulating stomatal
      closure in planta. In the present study, we assessed the contribution of passive
      (hydraulic) vs active (ABA mediated) mechanisms of stomatal closure in V.
      vinifera plants facing drought stress. Leaf gas exchange decreased progressively
      to zero during drought, and embolism-induced loss of hydraulic conductance in
      petioles peaked to ~50% in correspondence with strong daily limitation of
      stomatal conductance. Foliar ABA significantly increased only after complete
      stomatal closure had already occurred. Rewatering plants after complete stomatal
      closure and after foliar ABA reached maximum values did not induced stomatal re
      opening, despite embolism recovery and water potential rise. Our data suggest
      that in grapevine stomatal conductance is primarily regulated by passive
      hydraulic mechanisms. Foliar ABA apparently limits leaf gas exchange over long
      term, also preventing recovery of stomatal aperture upon rewatering, suggesting
      the occurrence of a mechanism of long-term down-regulation of transpiration to
      favor embolism repair and preserve water under conditions of fluctuating water
      availability and repeated drought events. 

PMID- 26207995
TI  - Generation and Characterization of Novel Magnetic Field-Responsive Biomaterials.
AB  - We report the preparation of novel magnetic field-responsive tissue substitutes
      based on biocompatible multi-domain magnetic particles dispersed in a fibrin
      agarose biopolymer scaffold. We characterized our biomaterials with several
      experimental techniques. First we analyzed their microstructure and found that it
      was strongly affected by the presence of magnetic particles, especially when a
      magnetic field was applied at the start of polymer gelation. In these samples we
      observed parallel stripes consisting of closely packed fibers, separated by more
      isotropic net-like spaces. We then studied the viability of oral mucosa
      fibroblasts in the magnetic scaffolds and found no significant differences
      compared to positive control samples. Finally, we analyzed the magnetic and
      mechanical properties of the tissue substitutes. Differences in microstructural
      patterns of the tissue substitutes correlated with their macroscopic mechanical
      properties. We also found that the mechanical properties of our magnetic tissue
      substitutes could be reversibly tuned by noncontact magnetic forces. This unique
      advantage with respect to other biomaterials could be used to match the
      mechanical properties of the tissue substitutes to those of potential target
      tissues in tissue engineering applications. 

PMID- 26207997
TI  - Evaluation of Spatial Pattern of Altered Flow Regimes on a River Network Using a
      Distributed Hydrological Model.
AB  - Alteration of the spatial variability of natural flow regimes has been less
      studied than that of the temporal variability, despite its ecological importance
      for river ecosystems. Here, we aimed to quantify the spatial patterns of flow
      regime alterations along a river network in the Sagami River, Japan, by
      estimating river discharge under natural and altered flow conditions. We used a
      distributed hydrological model, which simulates hydrological processes
      spatiotemporally, to estimate 20-year daily river discharge along the river
      network. Then, 33 hydrologic indices (i.e., Indicators of Hydrologic Alteration)
      were calculated from the simulated discharge to estimate the spatial patterns of
      their alterations. Some hydrologic indices were relatively well estimated such as
      the magnitude and timing of maximum flows, monthly median flows, and the
      frequency of low and high flow pulses. The accuracy was evaluated with
      correlation analysis (r > 0.4) and the Kolmogorov-Smirnov test (alpha = 0.05) by
      comparing these indices calculated from both observed and simulated discharge.
      The spatial patterns of the flow regime alterations varied depending on the
      hydrologic indices. For example, both the median flow in August and the frequency
      of high flow pulses were reduced by the maximum of approximately 70%, but these
      strongest alterations were detected at different locations (i.e., on the
      mainstream and the tributary, respectively). These results are likely caused by
      different operational purposes of multiple water control facilities. The results
      imply that the evaluation only at discharge gauges is insufficient to capture the
      alteration of the flow regime. Our findings clearly emphasize the importance of
      evaluating the spatial pattern of flow regime alteration on a river network where
      its discharge is affected by multiple water control facilities. 

PMID- 26207998
TI  - Cellular discrimination using in vitro Raman micro spectroscopy: the role of the
      nucleolus.
AB  - Raman micro spectroscopy has attracted considerable attention over the last few
      years to explore its possible clinical applications as a non-invasive powerful
      label-free in vitro screening tool in cancer diagnosis and monitoring,
      subcellular analysis of biochemical processes, drug uptake, mode of action and
      mechanisms of interaction as well as toxicity of, for example, chemotherapeutic
      agents. However, in order to evaluate accurately the potential of Raman micro
      spectroscopy for such applications it is essential to optimise measurement and
      data processing protocols associated with subcellular analysis. To this end, in
      vitro differentiation of cell lines is a basic proof of concept for the potential
      of the technique, and although many studies have indicated successful
      differentiation based on Raman micro spectroscopy, it is important, as the
      measurement and processing techniques are improved, to establish the biochemical
      and subcellular basis of that discrimination. In this study, Raman micro
      spectroscopy is used to compare and differentiate normal and cancer cells from
      human lung origin, A549 adenocarcinoma cell line, Calu-1 epidermoid non-small
      cell and BEAS-2B normal immortalized bronchial epithelium cell line. Spectra were
      taken from the three subcellular compartments, cytoplasm, nucleus and nucleolus
      and Principal Components Analysis was used to compare the spectral profiles
      between the cell lines and, coupled to Linear Discriminant Analysis, to explore
      the optimum sensitivity and specificity of discrimination. To support the
      analysis, Raman micro spectroscopy was coupled with Flow Cytometry, Confocal
      Laser Scanning Microscopy and Atomic Force Microscopy. While all subcellular
      regions can be employed to differentiate the normal and cancer cell lines,
      optimum discrimination sensitivity and specificity is achieved using the spectra
      from the nucleolar region alone. Notably, only the nucleolar spectral profiles
      differentiate the two cancer cell lines. The results point to the importance of
      the nucleolar regions in diagnostic applications of Raman microscopy as well as
      further applications in subcellular analysis of cytological processes. 

PMID- 26207996
TI  - LC-MS/MS Method for Serum Creatinine: Comparison with Enzymatic Method and Jaffe
      Method.
AB  - Accurate quantification of creatinine (Cre) is important to estimate glomerular
      filtration rate (GFR). Differences among various methods of Cre quantification
      were previously noted. This study aims to develop a liquid chromatography tandem
      mass spectrometry (LC-MS/MS) method for serum Cre and compare this method with
      clinical routine methods. LC-MS/MS analysis was performed on API 4000 triple
      quadrupole mass spectrometer coupled with an Agilent 1200 liquid chromatography
      system. After adding isotope-labeled Cre-d3 as internal standard, serum samples
      were prepared via a one-step protein precipitation with methanol. The LC-MS/MS
      method was compared with frequently used enzymatic method and Jaffe method. This
      developed method, with a total run time of 3 min, had a lower limit of
      quantification of 4.4 MUmol/L, a total imprecision of 1.15%-3.84%, and an average
      bias of 1.06%. No significant matrix effect, carryover, and interference were
      observed for the LC-MS/MS method. The reference intervals of serum Cre measured
      by LC-MS/MS assay were 41-79 MUmol/L for adult women, and 46-101 MUmol/L for
      adult men. Using LC-MS/MS as a reference, the enzymatic method showed an average
      bias of -2.1% and the Jaffe method showed a substantial average bias of 11.7%.
      Compared with the LC-MS/MS method, significant negative bias was observed for the
      enzymatic and Jaffe methods in hemolytic and lipimic samples. We developed a
      simple, specific, and accurate LC-MS/MS method to analyze serum Cre. Discordance
      existed among different methods. 

PMID- 26207999
TI  - Discovery and Synthesis of Boletopsins 13 and 14, Brominated Fungal Metabolites
      of Terrestrial Origin.
AB  - Here we report the discovery and synthesis of complex polybrominated p-terphenyl
      ethers isolated from a mushroom (Boletopsis sp.) used as a traditional medicine
      by the Kiovi people in the highlands of Papua New Guinea. Boletopsins 13 and 14
      represent the first report of polybrominated fungal metabolites to be produced by
      a terrestrial fungus. The synthetic method employs 2,4,4,6-tetrabromo-2,5
      cyclohexadienone to achieve selective polybromination of the extended aromatic
      system in a selective and sequential manner. 

PMID- 26208000
TI  - Synthesis of Diarylheptanoid Scaffolds Inspired by Calyxins I and J.
AB  - gamma,delta-Unsaturated alcohols are prepared efficiently in two steps from o
      hydroxycinnamaldehyde. The TMSOTf-mediated reaction of the gamma,delta
      unsaturated alcohols with aldehydes creates two oxygen heterocycles and three new
      stereocenters in a single pot. The approach is versatile, and by varying the
      boronic acid, Grignard reagent, and aldehyde, different substituents may be
      introduced, while use of a chiral base in the conjugate addition gives
      enantioenriched products. 

PMID- 26208002
TI  - Correction: Acid Hydrolysis and Molecular Density of Phytoglycogen and Liver
      Glycogen Helps Understand the Bonding in Glycogen alpha (Composite) Particles.

PMID- 26208001
TI  - A Simple and Rapid Identification Method for Mycobacterium bovis BCG with Loop
      Mediated Isothermal Amplification.
AB  - Bacillus Calmette-Guerin (BCG) is widely used as a live attenuated vaccine
      against Mycobacterium tuberculosis and is an agent for standard prophylaxis
      against the recurrence of bladder cancer. Unfortunately, it can cause severe
      infectious diseases, especially in immunocompromised patients, and the ability to
      immediately distinguish BCG from other M. tuberculosis complexes is therefore
      important. In this study, we developed a simple and easy-to-perform
      identification procedure using loop-mediated amplification (LAMP) to detect
      deletions within the region of difference, which is deleted specifically in all
      M. bovis BCG strains. Reactions were performed at 64  degrees C for 30 min and
      successful targeted gene amplifications were detected by real-time turbidity
      using a turbidimeter and visual inspection of color change. The assay had an
      equivalent detection limit of 1.0 pg of genomic DNA using a turbidimeter whereas
      it was 10 pg with visual inspection, and it showed specificity against 49 strains
      of 44 pathogens, including M. tuberculosis complex. The expected LAMP products
      were confirmed through identical melting curves in real-time LAMP procedures. We
      employed the Procedure for Ultra Rapid Extraction (PURE) kit to isolate
      mycobacterial DNA and found that the highest sensitivity limit with a minimum
      total cell count of mycobacterium (including DNA purification with PURE) was up
      to 1 * 10(3) cells/reaction, based on color changes under natural light with FDA
      reagents. The detection limit of this procedure when applied to artificial serum,
      urine, cerebrospinal fluid, and bronchoalveolar lavage fluid samples was also
      about 1 * 10(3) cells/reaction. Therefore, this substitute method using
      conventional culture or clinical specimens followed by LAMP combined with PURE
      could be a powerful tool to enable the rapid identification of M. bovis BCG as
      point-of-care testing. It is suitable for practical use not only in resource
      limited situations, but also in any clinical situation involving
      immunocompromised patients because of its convenience, rapidity, and cost
      effectiveness.

PMID- 26208004
TI  - Characterization of N-Glycan Structures on the Surface of Mature Dengue 2 Virus
      Derived from Insect Cells.
AB  - DENV envelope glycoprotein (E) is responsible for interacting with host cell
      receptors and is the main target for the development of a dengue vaccine based on
      an induction of neutralizing antibodies. It is well known that DENV E
      glycoprotein has two potential N-linked glycosylation sites at Asn67 and Asn153.
      The N-glycans of E glycoprotein have been shown to influence the proper folding
      of the protein, its cellular localization, its interactions with receptors and
      its immunogenicity. However, the precise structures of the N-glycans that are
      attached to E glycoprotein remain elusive, although the crystal structure of DENV
      E has been determined. This study characterized the structures of envelope
      protein N-linked glycans on mature DENV-2 particles derived from insect cells via
      an integrated method that used both lectin microarray and MALDI-TOF-MS. By
      combining these methods, a high heterogeneity of DENV N-glycans was found. Five
      types of N-glycan were identified on DENV-2, including mannose, GalNAc, GlcNAc,
      fucose and sialic acid; high mannose-type N-linked oligosaccharides and the
      galactosylation of N-glycans were the major structures that were found.
      Furthermore, a complex between a glycan on DENV and the carbohydrate recognition
      domain (CRD) of DC-SIGN was mimicked with computational docking experiments. For
      the first time, this study provides a comprehensive understanding of the N-linked
      glycan profile of whole DENV-2 particles derived from insect cells. 

PMID- 26208003
TI  - Demethylzeylasteral (T-96) Treatment Ameliorates Mice Lupus Nephritis Accompanied
      by Inhibiting Activation of NF-kappaB Pathway.
AB  - BACKGROUND: Inflammation plays a vital role in the pathogenesis in lupus
      nephritis (LN), which is largely attributable to the activation of nuclear factor
      kappa B (NF-kappaB) signal pathway. NF-kappaB up-regulates pro-inflammatory
      mediators, such as TNF-alpha, cyclo-oxygenase-2 (COX-2) and ICAM-1, and promotes
      macrophage infiltration into renal tissue, further inducing the progression of
      LN. Over the past 30 years, research has demonstrated that Tripterygium wilfordii
      Hook F (TWHF) possesses potent anti-inflammatory and immunosuppressive
      activities, and that demethylzeylasteral (T-96), an extract of TWHF, may be one
      of the responsible compounds. Here, we investigate the pharmacodynamic role and
      therapeutic mechanism by which T-96 suppresses inflammation and reduces renal
      pathology in the lupus-prone MRL/lpr mice. METHODS: Forty-eight MRL/lpr mice were
      equally randomly divided into 6 groups (1.2, 0.6 or 0.3 mg/10 g T-96, 0.022
      pills/10 g kang lang chuang san (one of Traditional Chinese herb as positive
      control), 0.125 mg/10 g prednisone and 0.1 ml/10 g normal saline as the LN
      disease control group). Also, eight WT C57BL/6 mice were used as normal control.
      After treatment by gavage with 0.10 ml/10 g/day volumes for 8 weeks, all mice
      were sacrificed and renal tissues were collected. The amount of 24 h proteinuria
      and the levels of anti-dsDNA antibody in serum were assessed respectively at
      weeks 0, 4 and 8. Inflammation, cytokines and NF-kappaB levels were assessed by
      histological examinations, immunohistochemical analyses and Western blot
      analyses. RESULTS: In comparison with untreated MRL/lpr mice, mice treated with
      1.2 and 0.6 mg/10 g of T-96 showed a significant improvement in 24 h proteinuria
      and the levels of anti-dsDNA antibody in serum. In addition, T-96 reduced the
      secretion of pro-inflammatory mediators such as TNF-alpha, COX-2 and ICAM-1, and
      the infiltration of macrophages in renal tissue. Moreover, T-96 significantly
      suppressed phosphorylations of cytoplasmic IKK and nuclear p65. CONCLUSION: This
      study suggests that T-96 exhibits reno-protective effects in LN accompanied by
      inhibiting the activation of NF-kappaB, reducing the downstream pro-inflammatory
      mediators and thus restricting macrophage infiltration. Because of these potent
      properties, T-96 should be considered as a promising therapeutic drug for LN.

PMID- 26208005
TI  - Herbivory and Competition of Tibetan Steppe Vegetation in Winter Pasture: Effects
      of Livestock Exclosure and Plateau Pika Reduction.
AB  - Rangeland degradation has been identified as a serious concern in alpine regions
      of western China on the Qinghai-Tibetan plateau (QTP). Numerous government
      sponsored programs have been initiated, including many that feature long-term
      grazing prohibitions and some that call for eliminating pastoralism altogether.
      As well, government programs have long favored eliminating plateau pikas
      (Ochotona curzoniae), assumed to contribute to degraded conditions. However,
      vegetation on the QTP evolved in the presence of herbivory, suggesting that
      deleterious effects from grazing are, to some extent, compensated for by reduced
      plant-plant competition. We examined the dynamics of common steppe ecosystem
      species as well as physical indicators of rangeland stress by excluding livestock
      and reducing pika abundance on experimental plots, and following responses for 4
      years. We established 12 fenced livestock exclosures within pastures grazed
      during winter by local pastoralists, and removed pikas on half of these. We
      established paired, permanent vegetation plots within and outside exclosures and
      measured indices of erosion and biomass of common plant species. We observed
      modest restoration of physical site conditions (reduced bare soil, erosion,
      greater vegetation cover) with both livestock exclusion and pika reduction. As
      expected in areas protected from grazing, we observed a reduction in annual
      productivity of plant species avoided by livestock and assumed to compete poorly
      when protected from grazing. Contrary to expectation, we observed similar
      reductions in annual productivity among palatable, perennial graminoids under
      livestock exclusion. The dominant grass, Stipa purpurea, displayed evidence of
      density-dependent growth, suggesting that intra-specific competition exerted a
      regulatory effect on annual production in the absence of grazing. Complete
      grazing bans on winter pastures in steppe habitats on the QTP may assist in the
      recovery of highly eroded pastures, but may not increase annual vegetative
      production. 

PMID- 26208006
TI  - Screening for Rheumatic Heart Disease among Peruvian Children: A Two-Stage
      Sampling Observational Study.
AB  - BACKGROUND: The objective of the study was to evaluate the implications of
      different classifications of rheumatic heart disease on estimated prevalence, and
      to systematically assess the importance of incidental findings from
      echocardiographic screening among schoolchildren in Peru. METHODS: We performed a
      cluster randomized observational survey using portable echocardiography among
      schoolchildren aged 5 to 16 years from randomly selected public and private
      schools in Arequipa, Peru. Rheumatic heart disease was defined according to the
      modified World Health Organization (WHO) criteria and the World Heart Federation
      (WHF) criteria. FINDINGS: Among 1395 eligible students from 40 classes and 20
      schools, 1023 (73%) participated in the present survey. The median age of the
      children was 11 years (interquartile range [IQR] 8-13 years) and 50% were girls.
      Prevalence of possible, probable and definite rheumatic heart disease according
      to the modified WHO criteria amounted to 19.7/1000 children and ranged from
      10.2/1000 among children 5 to 8 years of age to 39.8/1000 among children 13 to 16
      years of age; the prevalence of borderline/definite rheumatic heart disease
      according to the WHF criteria was 3.9/1000 children. 21 children (2.1%) were
      found to have congenital heart disease, 8 of which were referred for percutaneous
      or surgical intervention. CONCLUSIONS: Prevalence of RHD in Peru was considerably
      lower compared to endemic regions in sub-Saharan Africa, southeast Asia, and
      Oceania; and paralleled by a comparable number of undetected congenital heart
      disease. Strategies to address collateral findings from echocardiographic
      screening are necessary in the setup of active surveillance programs for RHD.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02353663.

PMID- 26208008
TI  - Prolonged QT: A rare cause of cardiac arrest.
AB  - A prolonged QT interval can be caused by medications, electrolyte abnormalities,
      or long QT syndrome, a genetic mutation that prolongs the action potential.
      Torsades de pointes is a potentially fatal polymorphic VT most often associated
      with prolonged QT interval. This article focuses on recognizing and treating drug
      induced torsades de pointes. 

PMID- 26208007
TI  - Medical Specialty Choice and Related Factors of Brazilian Medical Students and
      Recent Doctors.
AB  - BACKGROUND: Choosing a medical specialty is an important, complex, and not fully
      understood process. The present study investigated the factors that are related
      to choosing and rejecting medical specialties in a group of students and recent
      medical doctors. METHODOLOGY AND FINDINGS: A cross-sectional survey of 1,223
      medical students and doctors was performed in Brazil in 2012. A standardized
      literature-based questionnaire was applied that gathered preferable or rejected
      specialties, and asked questions about extracurricular experiences and the
      influence of 14 factors on a Likert-type scale from 0 to 4. Specialties were
      grouped according to lifestyle categories: controllable and uncontrollable, which
      were subdivided into primary care, internal medicine, and surgical specialties.
      Notably, the time period of rejection was usually earlier than the time period of
      intended choice (p < 0.0001, chi(2) = 107.2). The choice mainly occurred during
      the internship period in medical school (n = 466; 38.7%). An overall large
      frequency of participation in extracurricular activities was observed (n = 1,184;
      95.8%), which were highly associated with the respective medical area. Orthopedic
      surgery had the highest correlation with participation in specialty-specific
      organized groups (OR = 59.9, 95% CI = 21.6-166.3) and psychiatry was correlated
      with participation in research groups (OR = 18.0, 95% CI = 9.0-36.2). With regard
      to influential factors in controllable lifestyle specialties, "financial reason"
      (mean score +/- standard deviation: 2.8 +/- 1.0; median = 3) and "personal time"
      (3.1 +/- 1.3; median = 4) were important factors. In primary care, these factors
      were less important (1.7 +/- 1.3 and 1.7 +/- 1.5, respectively; median = 2 for
      both), and higher scores were observed for "curricular internship" (3.2 +/- 1.1,
      median = 4) and "social commitment" (2.6 +/- 1.3, median = 3). CONCLUSION: The
      present findings provide important insights into developing strategies to
      stimulate interest in specialties based on the needs of the Brazilian healthcare
      system.

PMID- 26208009
TI  - Navigating the gluten-free boom.
AB  - Gluten-free diets have gained popularity with the public at a rate greater than
      would be expected based on the prevalence of gluten-related disorders such celiac
      disease, nonceliac gluten sensitivity, and wheat allergy. This article reviews
      gluten-related disorders, indications for gluten-free diets, and the possible
      health benefits of gluten. Despite the health claims for gluten-free eating, no
      published experimental evidence supports weight-loss with a gluten-free diet or
      suggests that the general population would benefit from avoiding gluten. 

PMID- 26208010
TI  - Time for grief.

PMID- 26208011
TI  - The true cost of online PA education.

PMID- 26208013
TI  - My patient wants to try e-cigarettes to quit smoking. What should I say?
AB  - Electronic cigarettes are popular alternatives to actual cigarettes and are often
      used for smoking cessation. However, concerns about their efficacy and safety
      have resulted in calls for tighter regulation of their use. 

PMID- 26208014
TI  - An unusual cause of ventriculoperitoneal shunt infection.
AB  - Infection associated with ventriculoperitoneal (VP) shunt implantation can be a
      significant problem. VP shunt infection with Serratia marcescens, a gram-negative
      anaerobic rod, usually is related to underlying abdominal disease. This article
      describes treatment of two patients suffering from a VP shunt infection with S.
      marcescens without underlying abdominal disease. 

PMID- 26208015
TI  - Acute mitral valve regurgitation after acute coronary syndrome.
AB  - This article describes acute mitral valve regurgitation as a complication of
      myocardial infarction in a 66-year-old man presenting to the ED. 

PMID- 26208016
TI  - Fighting childhood obesity one game at a time.
AB  - Traditional video games contribute to a sedentary lifestyle. Active video games
      that include physical activity may help reduce childhood obesity and have found
      an unconventional niche in medical treatment and training. This article offers
      providers practical information on how to evaluate popular active video games and
      how to encourage patients to make them part of a more healthful lifestyle. 

PMID- 26208017
TI  - Exploring physician assistant data sources.
AB  - OBJECTIVES: To assess four physician assistant (PA) proprietary datasets and
      inform researchers about data quality for addressing healthcare policy and
      workforce questions. METHODS: The quality of datasets was assessed by experienced
      researchers. Descriptive analysis included overview, collection methodology,
      variables, and availability. Assessment included each dataset's strengths and
      limitations. RESULTS: Datasets from the American Academy of Physician Assistants,
      National Commission on Certification of Physician Assistants, Physician Assistant
      Education Association, and Optum Provider360 Database include overlap in
      variables reflecting organizational mission and/or design. Attributes include
      variables for validation; limitations were lack of public use files, requirements
      for specific data requests or data purchase. The datasets do not have unique
      identifiers and cannot easily be linked. CONCLUSIONS: The PA datasets contain
      variables of interest but are limited in scope. Better data collection and shared
      platforms could further the understanding of PA workforce characteristics and
      contributions to American healthcare. Researchers await more comprehensive,
      longitudinal, linked, and publicly available datasets.

PMID- 26208018
TI  - Hyperthyroidism.

PMID- 26208019
TI  - An unexpected finding in a woman who underwent laparoscopy.

PMID- 26208021
TI  - What is causing this patient's acute abdomen?

PMID- 26208022
TI  - Tightrope.

PMID- 26208023
TI  - Brace Yourself.

PMID- 26208024
TI  - Identifying Absolute Preferred Retinal Locations during Binocular Viewing.
AB  - PURPOSE: We present a new method for identifying the absolute location (i.e.,
      relative to the optic disc) of the preferred retinal location (PRL)
      simultaneously for the two eyes of patients with central vision loss. For this,
      we used a binocular eye-tracking system that determines the pupillary axes of
      both eyes without a user calibration routine. METHODS: During monocular viewing,
      we measured the pupillary axis and the angle between it and the visual axis
      (angle Kappa) for 10 eyes with normal vision. We also determined their fovea
      location relative to the middle of the optic disc with the MP-1 microperimeter.
      Then, we created a transformation between the eye-tracking and microperimeter
      measurements. We used this transformation to predict the absolute location of the
      monocular and binocular PRLs of nine patients with central vision loss. The
      accuracy of the monocular prediction was evaluated with the microperimeter. The
      binocular PRLs were checked for retinal correspondence and functionality by
      placing them on fundus photographs. RESULTS: The transformation yielded an
      average error for the monocular measures of 0.2 (95% confidence interval, 1.0 to 
      0.6 degrees) horizontally and 0.5 (95% confidence interval, 1.1 to -0.1 degrees)
      vertically. The predicted binocular measures showed that the PRLs were generally
      in corresponding locations in the two eyes. One patient whose PRLs were not in
      corresponding positions complained about diplopia. For all patients, at least one
      PRL fell onto functional retina during binocular viewing. CONCLUSIONS: This study
      shows that measurements of the location of the binocular PRLs relative to the
      pupillary axes can be transformed into absolute locations.

PMID- 26208028
TI  - Visual Illusions and the Brain.

PMID- 26208029
TI  - De Novo Assembly of the Donkey White Blood Cell Transcriptome and a Comparative
      Analysis of Phenotype-Associated Genes between Donkeys and Horses.
AB  - Prior to the mechanization of agriculture and labor-intensive tasks, humans used
      donkeys (Equus africanus asinus) for farm work and packing. However, as
      mechanization increased, donkeys have been increasingly raised for meat, milk,
      and fur in China. To maintain the development of the donkey industry, breeding
      programs should focus on traits related to these new uses. Compared to
      conventional marker-assisted breeding plans, genome- and transcriptome-based
      selection methods are more efficient and effective. To analyze the coding genes
      of the donkey genome, we assembled the transcriptome of donkey white blood cells
      de novo. Using transcriptomic deep-sequencing data, we identified 264,714
      distinct donkey unigenes and predicted 38,949 protein fragments. We annotated the
      donkey unigenes by BLAST searches against the non-redundant (NR) protein
      database. We also compared the donkey protein sequences with those of the horse
      (E. caballus) and wild horse (E. przewalskii), and linked the donkey protein
      fragments with mammalian phenotypes. As the outer ear size of donkeys and horses
      are obviously different, we compared the outer ear size-associated proteins in
      donkeys and horses. We identified three ear size-associated proteins, HIC1,
      PRKRA, and KMT2A, with sequence differences among the donkey, horse, and wild
      horse loci. Since the donkey genome sequence has not been released, the de novo
      assembled donkey transcriptome is helpful for preliminary investigations of
      donkey cultivars and for genetic improvement. 

PMID- 26208030
TI  - Treatment Frequency and Dosing Interval of Ranibizumab and Aflibercept for
      Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in the
      USA.
AB  - PURPOSE: To compare treatment patterns of intravitreal ranibizumab and
      aflibercept for the management of neovascular age-related macular degeneration
      (nAMD) in a real-world setting over the first 12 months of treatment. METHODS: A
      proprietary clinical database was used to identify treatment-naive patients with
      nAMD in the USA with claims for ranibizumab or aflibercept between November 1,
      2011 and November 30, 2013 and with follow-up of at least 12 months. Patients
      were considered treatment-naive if they had no anti-VEGF treatment code for 6
      months before the index date. Mean numbers of injections and of non-injection
      visits to a treating physician were compared between the two treatment cohorts
      (ranibizumab or aflibercept). In addition, the mean interval between doses was
      also investigated. RESULTS: Patient characteristics were similar for those
      receiving either ranibizumab (n = 5421) or aflibercept (n = 3506) at the index
      date. The mean (+/- standard deviation) numbers of injections received by
      patients treated with ranibizumab (4.9 +/- 3.3) or aflibercept (5.2 +/- 2.9) were
      not clinically different. The mean number of non-injection visits was 2.8 +/- 2.8
      and 2.1 +/- 2.5 for ranibizumab and aflibercept, respectively. Mean dosing
      interval was 51.0 days (+/- 41.8 days) in patients receiving ranibizumab and 54.1
      days (+/- 36.0 days) in those receiving aflibercept. Results were robust to
      sensitivity analyses for definition of treatment-naive, length of follow-up and
      treatment in the index eye only. CONCLUSIONS: Limited data exist regarding real
      world treatment patterns of aflibercept for the management of nAMD. Our results
      suggest that, in routine clinical practice, patients receive a comparable number
      of injections in the first year of treatment with ranibizumab or aflibercept.

PMID- 26208031
TI  - Synthesis of Nanocrystals and Particle Size Effects Studies on the Thermally
      Induced Spin Transition of the Model Spin Crossover Compound [Fe(phen)2(NCS)2].
AB  - Surfactant-free nanocrystals of the model spin-crossover compound
      [Fe(phen)2(NCS)2] (phen: 1,10-phenanthroline) have been synthesized applying the
      reverse micelle technique. The morphology of the nanocrystals, characterized by
      scanning electronic microscopy, corresponds to rhombohedric platelets with
      dimensions ranging from 203 * 203 * 106 nm to 142 * 142 * 74 nm. Variation of the
      concentration of the Fe(BF4)2.6H2O salt in the synthesis has been found to have
      little influence on the crystallite size. In contrast, the solvent-surfactant
      ratio (omega) is critical for a good particle growth. The spin transition of the
      nanocrystals has been characterized by magnetic susceptibility measurements and
      Mossbauer spectroscopy. The nanocrystals undergo an abrupt and more cooperative
      spin transition in comparison with the bulk compound. The spin transition is
      centered in the interval of temperature of 175-185 K and is accompanied by 8 K of
      thermal hysteresis width. The crystallite quality more than the crystallite size
      is responsible for the higher cooperativity. The magnetic properties of the
      nanocrystals embedded in organic polymers such as polyethylene glycol, nujol,
      glycerol, and triton have been studied as well. The spin transition in the
      nanocrystals is affected by the polymer coating. The abrupt and first-order spin
      transition transforms into a more continuous spin transition as a result of the
      chemical pressure asserted by the organic polymers on the Fe(II) centers. 

PMID- 26208032
TI  - Development and Characterization of a Human Reporter Cell Line for the Assessment
      of Thyroid Receptor Transcriptional Activity: A Case of Organotin Endocrine
      Disruptors.
AB  - We developed and characterized the human luciferase reporter cell line PZ-TR for
      the assessment of thyroid receptor (TR) transcriptional activity.
      Triiodothyronine (T3) induced luciferase activity in a dose-dependent manner, and
      the sensitivity of assay allowed for the detection of nanomolar T3
      concentrations. The luciferase activity was induced by a maximum of (2.42 +/-
      0.14)-(2.73 +/- 0.23)-fold after 24 h of exposure to 10 nM T3. We did not observe
      a nonspecific induction of luciferase activity by other steroid hormones and VDR
      ligands, with the exception of partial activation by retinoic acids.
      Cryopreservation of PZ-TR cells did not influence their functionality,
      responsivity to T3, or cell morphology, even after long-term cultivation. PZ-TR
      cells were used to evaluate the effects of organic tin compounds on TR. We found
      that the tributyltin and triphenyltin derivatives induced luciferase activity and
      that application of organotins in combination with T3 enhanced the effect of T3.
      These findings indicate that organic tin compounds have potential to interfere
      with TR-mediated regulation of gene expression and influence the physiological
      activity of thyroid hormones. 

PMID- 26208034
TI  - Mesenchymal stem cell treatment in hyperoxia-induced lung injury in newborn rats.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of tracheally
      delivered mesenchymal stem cells (MSC) on lung pathology in a hyperoxia-induced
      lung injury (HILI) model in neonatal rats. METHODS: For the HILI model, rat pups
      were exposed to 85-95% oxygen during the first 10 days of life. Rats were divided
      into six groups: room-air normoxia (n = 11); room air, sham (n = 11); hyperoxia
      exposed with normal saline as placebo (n = 9); hyperoxia exposed with culture
      medium of MSC (n = 10); hyperoxia exposed with medium remaining after harvesting
      of MSC (n = 8); and hyperoxia exposed with MSC (n = 17). Pathologic changes,
      number and diameter of alveoli, alpha-smooth muscle actin (alpha-SMA) expression
      and localization of MSC in the lungs were assessed. RESULTS: Number of alveoli
      increased and alveolar diameter decreased in the mesenchymal stem cell group so
      that there were no differences when compared with the normoxia group (P = 0.126
      and P = 0.715, respectively). Expression of alpha-SMA decreased significantly in
      the mesenchymal stem cell group compared with the placebo group (P < 0001). Green
      fluorescent protein-positive cells were found in lung tissue from all rats given
      MSC. Some green fluorescent protein-positive MSC also expressed surfactant
      protein-C. CONCLUSION: Mesenchymal stem cells became localized in damaged lung
      tissue, and recovery approximated the room air control.

PMID- 26208035
TI  - Liquid Chromatographic Analysis of the Interaction between Amino Acids and
      Aromatic Surfaces Using Single-Wall Carbon Nanotubes.
AB  - Proteins have nonspecific adsorption capacities for solid surfaces. Although the
      nonspecific adsorption capacities are generally understood to be related to the
      hydrophobicity or charge density of the surfaces, little is known at the amino
      acid level about the interaction between proteins and polyaromatic surfaces such
      as carbon nanotubes, which have recently been used for biotechnology
      applications. In this study, we investigated the interaction between
      proteinogenic amino acids and carbon nanotubes using high-performance liquid
      chromatography on silica matrices coated by single-wall carbon nanotubes
      (SWCNTs). Among the amino acids used in this study, tryptophan, tyrosine, and
      phenylalanine showed exceptional affinity for the matrices. The characteristic
      affinities of these amino acids were ascribed to their unique interactions with
      the large polyaromatic surfaces of the SWCNTs. These results are useful for
      understanding and controlling protein adsorption onto aromatic surfaces. 

PMID- 26208036
TI  - FVIII inhibitor development according to concentrate: data from the EUHASS
      registry excluding overlap with other studies.

PMID- 26208038
TI  - Evaluation of zirconia-porcelain interface using X-ray diffraction.
AB  - The aim of this study was to determine if accelerated aging of porcelain
      veneering had an effect on the surface properties specific to a tetragonal-to
      monoclinic transformation (TMT) of zirconia restorations. Thirty-six zirconia
      samples were milled and sintered to simulate core fabrication followed by
      exposure to various combinations of surface treatments including as-received
      (control), hydrofluoric acid (HF), application of liner plus firings, application
      of porcelain by manual layering and pressing with firing, plus accelerated aging.
      The quantity of transformed tetragonal to monoclinic phases was analyzed utilized
      an X-ray diffractometer and one-way analysis of variance was used to analyze
      data. The control samples as provided from the dental laboratory after milling
      and sintering process had no TMT (Xm = 0). There was an effect on zirconia
      samples of HF application with TMT (Xm = 0.8%) and liner plus HF application with
      TMT (Xm = 8.7%). There was an effect of aging on zirconia samples (no veneering)
      with significant TMT (Xm = 70.25%). Both manual and pressing techniques of
      porcelain applications reduced the TMT (manual, Xm = 4.41%, pressing, Xm =
      11.57%), although there was no statistical difference between them. It can be
      concluded that simulated applications of porcelain demonstrated the ability to
      protect zirconia from TMT after aging with no effect of a liner between different
      porcelain applications. The HF treatment also caused TMT.

PMID- 26208040
TI  - BCR-ABL1 b3a2 and b2a2 transcripts in chronic myeloid leukemia: does it matter?

PMID- 26208039
TI  - PiggyBac transposon-mediated gene delivery efficiently generates stable
      transfectants derived from cultured primary human deciduous tooth dental pulp
      cells (HDDPCs) and HDDPC-derived iPS cells.
AB  - The ability of human deciduous tooth dental pulp cells (HDDPCs) to differentiate
      into odontoblasts that generate mineralized tissue holds immense potential for
      therapeutic use in the field of tooth regenerative medicine. Realization of this
      potential depends on efficient and optimized protocols for the genetic
      manipulation of HDDPCs. In this study, we demonstrate the use of a PiggyBac (PB)
      based gene transfer system as a method for introducing nonviral transposon DNA
      into HDDPCs and HDDPC-derived inducible pluripotent stem cells. The transfection
      efficiency of the PB-based system was significantly greater than previously
      reported for electroporation-based transfection of plasmid DNA. Using the
      neomycin resistance gene as a selection marker, HDDPCs were stably transfected at
      a rate nearly 40-fold higher than that achieved using conventional methods. Using
      this system, it was also possible to introduce two constructs simultaneously into
      a single cell. The resulting stable transfectants, expressing tdTomato and
      enhanced green fluorescent protein, exhibited both red and green fluorescence.
      The established cell line did not lose the acquired phenotype over three months
      of culture. Based on our results, we concluded that PB is superior to currently
      available methods for introducing plasmid DNA into HDDPCs. There may be
      significant challenges in the direct clinical application of this method for
      human dental tissue engineering due to safety risks and ethical concerns.
      However, the high level of transfection achieved with PB may have significant
      advantages in basic scientific research for dental tissue engineering
      applications, such as functional studies of genes and proteins. Furthermore, it
      is a useful tool for the isolation of genetically engineered HDDPC-derived stem
      cells for studies in tooth regenerative medicine.

PMID- 26208043
TI  - Ultra-thin Cu2S nanosheets: effective cocatalysts for photocatalytic hydrogen
      production.
AB  - Herein, we achieved successful synthesis of 2D Cu2S nanosheets (NS) with a
      thickness of 1.2 nm by a novel strategy. The key to obtain ultra-thin Cu2S NS was
      the use of a unique sulfur precursor which not only supplied sulfur in a
      controlled manner, but also directed the formation of a 2D structure. The as
      prepared Cu2S NS were proved to be effective cocatalysts for photocatalytic
      hydrogen production. The H2 production rate of Cu2S NS/TiO2 reached 1430.4 MUmol
      g(-1) h(-1), which was 4.9 times higher than that of TiO2. 

PMID- 26208037
TI  - The role of microRNAs in bone remodeling.
AB  - Bone remodeling is balanced by bone formation and bone resorption as well as by
      alterations in the quantities and functions of seed cells, leading to either the
      maintenance or deterioration of bone status. The existing evidence indicates that
      microRNAs (miRNAs), known as a family of short non-coding RNAs, are the key post
      transcriptional repressors of gene expression, and growing numbers of novel
      miRNAs have been verified to play vital roles in the regulation of osteogenesis,
      osteoclastogenesis, and adipogenesis, revealing how they interact with signaling
      molecules to control these processes. This review summarizes the current
      knowledge of the roles of miRNAs in regulating bone remodeling as well as novel
      applications for miRNAs in biomaterials for therapeutic purposes.

PMID- 26208041
TI  - Localized movement and morphology of UBF1-positive nucleolar regions are changed
      by gamma-irradiation in G2 phase of the cell cycle.
AB  - The nucleolus is a well-organized site of ribosomal gene transcription. Moreover,
      many DNA repair pathway proteins, including ATM, ATR kinases, MRE11, PARP1 and
      Ku70/80, localize to the nucleolus (Moore et al., 2011 ). We analyzed the
      consequences of DNA damage in nucleoli following ultraviolet A (UVA), C (UVC), or
      gamma-irradiation in order to test whether and how radiation-mediated genome
      injury affects local motion and morphology of nucleoli. Because exposure to
      radiation sources can induce changes in the pattern of UBF1-positive nucleolar
      regions, we visualized nucleoli in living cells by GFP-UBF1 expression for
      subsequent morphological analyses and local motion studies. UVA radiation, but
      not 5 Gy of gamma-rays, induced apoptosis as analyzed by an advanced
      computational method. In non-apoptotic cells, we observed that gamma-radiation
      caused nucleolar re-positioning over time and changed several morphological
      parameters, including the size of the nucleolus and the area of individual UBF1
      positive foci. Radiation-induced nucleoli re-arrangement was observed
      particularly in G2 phase of the cell cycle, indicating repair of ribosomal genes
      in G2 phase and implying that nucleoli are less stable, thus sensitive to
      radiation, in G2 phase. 

PMID- 26208044
TI  - Towards efficient chemical synthesis via engineering enzyme catalysis in
      biomimetic nanoreactors.
AB  - Biocatalysis with immobilized enzymes as catalysts holds enormous promise in
      developing more efficient and sustainable processes for the synthesis of fine
      chemicals, chiral pharmaceuticals and biomass feedstocks. Despite the appealing
      potentials, nowadays the industrial-scale application of biocatalysts is still
      quite modest in comparison with that of traditional chemical catalysts. A
      critical issue is that the catalytic performance of enzymes, the sophisticated
      and vulnerable catalytic machineries, strongly depends on their intracellular
      working environment; however the working circumstances provided by the support
      matrix are radically different from those in cells. This often leads to various
      adverse consequences on enzyme conformation and dynamic properties, consequently
      decreasing the overall performance of immobilized enzymes with regard to their
      activity, selectivity and stability. Engineering enzyme catalysis in support
      nanopores by mimicking the physiological milieu of enzymes in vivo and
      investigating how the interior microenvironment of nanopores imposes an influence
      on enzyme behaviors in vitro are of paramount significance to modify and improve
      the catalytic functions of immobilized enzymes. In this feature article, we have
      summarized the recent advances in mimicking the working environment and working
      patterns of intracellular enzymes in nanopores of mesoporous silica-based
      supports. Especially, we have demonstrated that incorporation of polymers into
      silica nanopores could be a valuable approach to create the biomimetic
      microenvironment for enzymes in the immobilized state. 

PMID- 26208045
TI  - Quality of life and menstruation in adolescents.
AB  - PURPOSE OF REVIEW: Menstrual problems are known to be common amongst teenagers,
      but adequate recognition of the impact this may have on the adolescent and
      appropriate interventions that are focussed on the needs of the adolescents are
      limited. RECENT FINDINGS: To date, the impact of menstrually related problems on
      the quality of life of adolescents has been poorly studied. Although some studies
      report on the impact of, in particular, dysmenorrhoea on school absenteeism, less
      is known about the impact on psychosocial functioning. For other menstrual
      problems, even less is known. It is increasingly recognized that understanding
      the impact on quality of life is an important measure to better understand the
      impact of the health problem and also to ensure the optimal delivery of patient
      centred healthcare. This review will explore the current tools available for
      assessment of quality of life in adolescents and then focus on the specific
      menstrual problems (dysmenorrhoea, heavy menses, oligo/amenorrhoea) and what is
      known about their impact on the general well being of young women. SUMMARY:
      Cultural differences in the presentation and impact of menstrual problems appear
      to be present with a greater impact on psychosocial functioning found with
      particularly oligo/amenorrhoea. There is clearly room for further study to
      explore and then optimize care.

PMID- 26208046
TI  - Parentification, Stress, and Problem Behavior of Adolescents who have a Parent
      with Mental Health Problems.
AB  - When adolescents live with a parent with mental illness, they often partly take
      over the parental role. Little is known about the consequences of this so-called
      parentification on the adolescents' internalizing and externalizing problems.
      This survey study examined this effect cross-sectionally and longitudinally in a
      sample of 118 adolescents living with a parent suffering from mental health
      problems. In addition, the study examined a possible indirect effect via
      perceived stress. Path analyses were used to examine the direct associations
      between parentification and problem behavior as well as the indirect relations
      via perceived stress. The results showed that parentification was associated with
      both internalizing and externalizing problems cross-sectionally, but it predicted
      only internalizing problems 1 year later. An indirect effect of parentification
      on adolescent internalizing and externalizing problems via perceived stress was
      found, albeit only cross-sectionally. These findings imply that parentification
      can be stressful for adolescents who live with a parent with mental health
      problems, and that a greater awareness of parentification is needed to prevent
      adolescents from developing internalizing problems.

PMID- 26208048
TI  - Poorer Drinking Outcomes with Citalopram Treatment for Alcohol Dependence: A
      Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - BACKGROUND: Previous research on the use of selective serotonin reuptake
      inhibitors (SSRIs) as a treatment for alcohol dependence has yielded mixed
      results. Depression has been shown to be a predictor of relapse and poor outcome
      following treatment, and it has been hypothesized that SSRIs would be beneficial
      in reducing drinking in depressed alcohol-dependent individuals. This randomized,
      double-blind, placebo-controlled trial was designed to test the effects of
      citalopram on treatment outcomes among alcohol-dependent individuals with and
      without depression. METHODS: Two hundred and sixty-five patients meeting criteria
      for a DSM-IV diagnosis of alcohol abuse or dependence were randomly assigned to
      receive placebo or citalopram 20 mg per day for the first week, followed by 40 mg
      per day from weeks 2 through 12. All patients received a standard course of
      treatment consisting of weekly individual and group psychotherapy. Participants
      were reassessed at 12 weeks, including dropouts from both treatment groups to
      determine rates of abstinence, changes in alcohol use, addiction severity,
      depressive symptoms, and psychiatric status. RESULTS: Citalopram provided no
      advantage over placebo in terms of treatment outcomes, and for some measures,
      citalopram produced poorer outcomes. Patients in the citalopram group had a
      higher number of heavy drinking days throughout the trial, and smaller changes in
      frequency and amount of alcohol consumption at 12 weeks. There was no influence
      of depression severity on outcomes in either medication group. Survival analyses
      also indicated no differences between depressed and nondepressed patients in the
      citalopram group for time to first slip or relapse. A diagnosis of personality
      disorder was associated with poorer treatment responses overall, regardless of
      treatment condition. CONCLUSIONS: This trial does not support the use of
      citalopram in the treatment of alcohol dependence. The results suggest that the
      use of SSRIs among depressed and nondepressed alcohol-dependent individuals early
      in recovery, prior to the onset of abstinence, may be contraindicated.

PMID- 26208049
TI  - ?

PMID- 26208047
TI  - An EG-VEGF-Dependent Decrease in Homeobox Gene NKX3.1 Contributes to
      Cytotrophoblast Dysfunction: A Possible Mechanism in Human Fetal Growth
      Restriction.
AB  - Idiopathic fetal growth restriction (FGR) is frequently associated with placental
      insufficiency. Previous reports have provided evidence that endocrine gland
      derived vascular endothelial growth factor (EG-VEGF), a placental secreted
      protein, is expressed during the first trimester of pregnancy, controls both
      trophoblast proliferation and invasion, and its increased expression is
      associated with human FGR. In this study, we hypothesize that EG-VEGF-dependent
      changes in placental homeobox gene expressions contribute to trophoblast
      dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene
      expressions were determined using a homeobox gene cDNA array on placental
      explants of 8-12 wks gestation after stimulation with EG-VEGF in vitro for 24 h.
      The homeobox gene array identified a greater-than-five-fold increase in HOXA9,
      HOXC8, HOXC10, HOXD1, HOXD8, HOXD9 and HOXD11, while NKX 3.1 showed a greater
      than-two-fold decrease in mRNA expression compared with untreated controls.
      Homeobox gene NKX3.1 was selected as a candidate because it is a downstream
      target of EG-VEGF and its expression and functional roles are largely unknown in
      control and idiopathic FGR-affected placentae. Real-time PCR and immunoblotting
      showed a significant decrease in NKX3.1 mRNA and protein levels, respectively, in
      placentae from FGR compared with control pregnancies. Gene inactivation in vitro
      using short-interference RNA specific for NKX3.1 demonstrated an increase in BeWo
      cell differentiation and a decrease in HTR-8/SVneo proliferation. We conclude
      that the decreased expression of homeobox gene NKX3.1 downstream of EG-VEGF may
      contribute to the trophoblast dysfunction associated with idiopathic FGR
      pregnancies.

PMID- 26208050
TI  - ?

PMID- 26208052
TI  - ?

PMID- 26208051
TI  - ?

PMID- 26208053
TI  - ?

PMID- 26208054
TI  - ?

PMID- 26208055
TI  - ?

PMID- 26208056
TI  - ?

PMID- 26208058
TI  - ?

PMID- 26208057
TI  - ?

PMID- 26208059
TI  - ?

PMID- 26208060
TI  - A Simple Microplate Method with Improved Low Iodine Concentration Sensitivity in
      Urinary Iodine Measurement.

PMID- 26208061
TI  - Evidence-based Update of Pediatric Dental Restorative Procedures: Preventive
      Strategies.
AB  - BACKGROUND: There has been significant advances in the understanding of
      preventive restorative procedures regarding the advantages and disadvantages for
      restorative procedures; the evidence for conservative techniques for deep carious
      lesions; the effectiveness of pit and fissure sealants; and the evidence for use
      of resin infiltration techniques. AIM: The intent of this review is to help
      practitioners use evidence to make decisions regarding preventive restorative
      dentistry in children and young adolescents. STUDY DESIGN: This evidence-based
      review appraises the literature, primarily between the years 1995-2013, on
      preventive restorative strategies. The evidence was graded as to strong evidence,
      evidence in favor, or expert opinion by consensus of authors Results: The
      preventive strategy for dental caries includes individualized assessment of
      disease progression and management with appropriate preventive and restorative
      therapy. There is strong evidence that restoration of teeth with incomplete
      caries excavation results in fewer signs and symptoms of pulpal disease than
      complete excavation. There is strong evidence that sealants should be placed on
      pit and fissure surfaces judged to be at risk for dental caries, and surfaces
      that already exhibit incipient, non-cavitated carious lesions. There is evidence
      in favor for resin infiltration to improve the clinical appearance of white spot
      lesions. CONCLUSIONS: Substantial evidence exists in the literature regarding the
      value of preventive dental restorative procedures.

PMID- 26208062
TI  - Meta-Analysis of Observational Studies on the Most Commonly Missing Permanent
      Dentition (Excluding the Third Molars) in Non-Syndromic Dental Patients or
      Randomly-Selected Subjects, and the Factors Affecting the Observed Rates.
AB  - PURPOSE: The aim of this study was to summarize the literature on the most
      frequently missing permanent teeth excluding the third molars. STUDY DESIGN: A
      search was conducted to find all the available literature (in various scientific
      and general databases) regarding the most commonly missing teeth with respect to
      ethnicity and time, as well as factors biasing this outcome. Quality assessment
      was done to exclude studies with inconsistent information, poor designs, or data
      pertaining to syndromic cases or the third molars. The role of biasing factors
      was as well quantitatively assessed using statistical analyses [Q-test, Egger
      regression, Spearman correlation coefficient, multiple linear regression, Welch t
      test] (alpha=0.05). RESULTS: A total of 81 reports was included. The meta-sample
      was heterogeneous (P=0.000, Q-test). No significant publication bias was detected
      (P>0.1, Egger regression). The mandibular second premolar was reported as the
      most commonly missing tooth in most studies, followed by the maxillary lateral
      (the most commonly missing in the rest). In terms of the missing share of each
      tooth percent of all missing teeth, the mandibular second premolar and incisors
      are more likely to be absent, followed by the maxillary second premolar and
      lateral. The absence of different teeth can be affected by the ethnicity, sample
      types (epidemiological or dental patients), sample sizes (only in the case of
      bimaxillary second premolars), and the minimum ages of pooled subjects (only in
      the case of the maxillary lateral and the mandibular second premolar).
      CONCLUSIONS: Since enrolling younger patients can bias the results, older
      patients should be sampled.

PMID- 26208063
TI  - Comparison between Clinical Aspects and Salivary Microbial Profile of Children
      with and without Early Childhood Caries: A Preliminary Study.
AB  - PURPOSE: To compare the clinical aspects and microbial profile of children with
      and without early childhood caries (ECC). STUDY DESIGN: 14 patients (7 without
      caries and 7 with ECC) were submitted to anamnesis, clinical exam and saliva
      collection for microbiological analyses. Counts of Streptococcus mutans,
      Lactobacillus spp. Candida spp., and total microorganisms were performed by
      culture methods. Microbial diversity was characterized by PCR-DGGE.
      Demographic/clinical data and salivary microbial counts were compared between
      groups. RESULTS: Habits of hygiene and breastfeeding presented no association
      with ECC. Use of pacifiers was associated with absence of caries (p=0.035).
      Counts of total microorganisms and Candida spp. did not differ between the
      groups. The ECC group presented larger quantity of S. mutans (p=0.026) and
      Lactobacillus spp. (p=0.002). There was no correlation between microorganisms and
      breastfeeding and pacifier use. The dmf-t of ECC Group was 10.5 +/- 1.9 and the
      modified dmf-t was 11.3 +/- 3.6. The DGGE demonstrated difference in the pattern
      of bands between the groups. CONCLUSION: Pacifiers usage was associated with the
      absence of ECC and microorganism number was higher in the caries group. The PCR
      DGGE revealed a characteristic microbial diversity in the ECC Group, being an
      excellent tool for observing the dynamics of the salivary microbial community in
      these patients.

PMID- 26208064
TI  - Intrusive Luxation in Primary Teeth: A Case Report.
AB  - BACKGROUND: Intrusive luxation, also called central dislocation, is often the
      result of an axial impact in the apical direction, moving the tooth within the
      alveolar bone. This is possibly one of the most traumatic injuries, since the
      displacement of a tooth within its socket implies extensive and acute involvement
      of the periodontal ligament, bone damage and rupture of the neurovascular bundle.
      The close relationship between the apexes of the primary teeth and the developing
      permanent successor in turn can lead to multiple complications, which are greater
      when the permanent tooth is affected in the early stages of development. METHODS:
      The present paper describes a case of intrusion in primary teeth and its
      evolution following initial diagnosis as avulsion at the time of trauma. RESULTS:
      The upper right central incisor, initially diagnosed as avulsed, was lodged in
      the floor of the right nostril, and was surgically extracted through the nose.
      CONCLUSIONS: In cases of intrusion of primary teeth, it is essential to diagnose
      the direction of the displaced tooth to rule out injury to the successor and thus
      prevent the occurrence of sequelae in the permanent dentition.

PMID- 26208065
TI  - Distribution of Molar Incisor Hypomineralization in Malaysian Children Attending
      University Dental Clinic.
AB  - OBJECTIVES: Molar-Incisor Hypomineralization (MIH) is a condition of
      hypomineralized enamel of systemic origin affecting first permanent molars and
      frequently permanent incisors. It is considered a global problem and data from
      South-East Asian countries, including Malaysia are lacking. Hence the aim of this
      study were to investigate the distribution and severity of MIH in a group of
      children aged 7-12 year olds attending pediatric dental clinic at Faculty of
      Dentistry, Universiti Teknologi MARA (UiTM), Malaysia. STUDY DESIGN: Hundred and
      fifty four children age 7-12 year-old with mean age of 9.14 +/-1.682 had their
      first permanent molars and permanent incisors were examined at Faculty of
      Dentistry, UiTM using European Academy of Paediatric Dentistry 2003 (EAPD)
      criteria for diagnosis of MIH. Children at least one first permanent molar
      affected were considered as having MIH. Data were recorded and statistically
      analysed using descriptive analysis and Chi square test. RESULTS: Twenty six of
      the total examined children (n=154) had MIH (16.9%). There was no statistical
      difference between males and females in the prevalence of MIH. However, a
      statistical significant difference was found by age groups. The first permanent
      molars were more frequently affected (58%) as compared to permanent incisors.
      Mandibular molars were to have the highest rate of MIH (15.5%). The right and
      left sides were equally affected. Mild defects were the most frequent lesion type
      (96.6%). CONCLUSIONS: This study revealed that MIH is a common condition (16.9%).
      Molars were more frequently affected than incisors with mild defects were the
      most common lesion status. Further studies on this defect amongst Malaysian
      children are worthwhile.

PMID- 26208066
TI  - Effect of Smear Layers Created by Different Burs on Durability of Self-Etching
      Adhesive Bond to Dentin of Primary Teeth.
AB  - AIM: The aim of this study was to evaluate the effects of a smear layer generated
      by a high-speed diamond or carbide bur on the durability of microtensile bond
      strength (MUTBS) of a self-etching adhesive to primary dentin. STUDY DESIGN: Flat
      occlusal dentin surfaces of 105 human primary molars were exposed using 600 grit
      silicon carbide paper before being divided into 2 groups for further grinding
      with either a highspeed diamond or carbide bur. Ten prepared dentin surfaces
      treated by each bur were evaluated for the characteristics of the smear layer
      using a scanning electron microscope (SEM). Seventy-five specimens from each bur
      prepared group were applied with a 2-step self-etching adhesive (Clearfil SE
      Bond((r))) then built up with a resin composite. Each bonded specimen was
      sectioned into a 1-mm thick slab and trimmed to a dumbbell shape with a cross
      sectional area of approximately 1 mm(2). All slabs were divided into 3 groups
      (n=25) according to 3 storage times of 24 hrs, 3 months, and 6 months, in
      distilled water at 37 degrees C. After storage, the MUTBS was determined using a
      universal testing machine. All fracture specimens were prepared for observation
      of failure modes. Ten bonded specimens of each bur group were prepared for
      observation of the resin-dentin interface using an SEM. Smear-layer thickness,
      MUTBS, and failure mode distributions were statistically analyzed. RESULTS: The
      high speed carbide bur created a significantly thinner smear layer than the
      diamond bur (p < 0.05). Dentin surfaces treated with a high-speed carbide bur
      generally obtained significantly higher MUTBS than the diamond bur group (p <
      0.05). The MUTBS gradually decreased over time such that specimens stored for 6
      months had significantly lower bond strength than those stored for 24 hrs (p <
      0.05). Self-etching adhesive created a hybrid layer of the same thickness when
      prepared with either a carbide bur or diamond bur, but the carbide bur group had
      longer and more resin tags. CONCLUSION: Highspeed carbide bur groups had a higher
      MUTBS than diamond bur groups for all storage times, and bond strengths decreased
      over time in both substrate groups. The use of a carbide bur produced a thinner
      smear layer and therefore is recommended when using this 2-step self-etching
      adhesive to bond the resin composite to primary dentin.

PMID- 26208067
TI  - A New Classification System for Unilateral Cleft Lip and Palate Infants to assist
      Presurgical Infant Orthopedics.
AB  - The proposed advantages of pre-surgical naso-alveolar moulding (PNAM) are easy
      primary lip repair which heals under minimum tension reducing the scar formation
      and improving the aesthetic results in addition to reshaping of alar cartilage
      and improvement of nasal symmetry.However, the anatomy and alveolar morphology
      varies for each cleft child; the procedure for PNAM differs accordingly. In an
      attempt to categorize unilateral cleft lip and palate cases as per anatomical
      variations, a new classification system has been proposed. This classification
      aims to give an insight in unilateral cleft morphology based on which
      modification in PNAM procedure could be done. 

PMID- 26208068
TI  - Cytotoxicity of Fast-set Conventional and Resin-modified Glass Ionomer Cement
      Polymerized at Different Times on SHED.
AB  - OBJECTIVES: To compare the cytotoxicity of conventional GIC and Resin Modified
      GIC (RMGIC) polymerized at 2 different times on stem cells from human exfoliated
      deciduous teeth (SHED). STUDY DESIGN: The conventional GIC (Fuji IX GP Extra) and
      RMGIC (Fuji II LC) were mixed and incubated in a prepared Dublecco's Modified
      Eagle Medium (DMEM) for seven days. After seeding the characterized SHED for 24
      hrs, six replicates of seven serially diluted extracts of each group were added
      and incubated for 72 hrs. MTT test was used for cytotoxicity evaluation and the
      data were analysed using Kruskal-Wallis followed by Mann-Whitney test, with the
      statistical significance set at P<0.05. RESULTS: The half maximal inhibitory
      concentration (IC50) was found at 45.0 mg/ml, 45.0 mg/ml and 31.25 mg/ml for Fuji
      IX, Fuji II LC (40s) and Fuji II LC (20s), respectively. Significantly different
      cytotoxic effects were found between Fuji II LC polymerized at 20 secs and 40
      secs, and between Fuji IX and Fuji II LC (20s) (P<0.05), and these were observed
      in all concentrations except for 50 mg/ml. CONCLUSIONS: RMGIC polymerized at 20
      secs exhibited the least favorable cell viability among all groups. Nevertheless,
      the cell viability was comparable to conventional GICs when the manufacturer's
      recommended time was doubled (40 secs).

PMID- 26208069
TI  - Flexural and Microtensile Bond Strength of Bulk Fill Materials.
AB  - AIM: The aim of this study was to evaluate the flexural and MUTBS of bulk-fill
      materials. STUDY DESIGN: Bulk-fill materials SDR, X-trabase (XTR) and
      TetricEvoCeramBulkFill (EVO) were used in this study. To test flexural strength,
      25x2x2mm samples were prepared and tested with three point bending test. To test
      the microtensile bond strength (MUTBS), two blocks (4x4x4mm) were prepared for
      each material. In Group A+B, acid-etching was applied to the surface of one of
      these blocks and no acid-etching was applied in Group B. After applying bonding
      agent, two blocks were placed into the mold and composite resin (COMP; Tetric N
      Ceram) was applied with incremental layering. To evaluate the MUTBS of primary
      dentin, the bulk-fill materials were applied to flat dentin up to 4mm. The new
      blocks and the teeth were sectioned to obtain sticks and the sticks were loaded
      in tension until failure. Flexural and microtensile bond strength was calculated
      based on failure load. RESULTS: The ranking of materials with regards to flexural
      strength values were SDR>XTR>EVO>COMP,respectively. In GroupA+B, the MUTBS values
      were XTR>SDR>EVO and were XTR>EVO>SDR in GroupB (p>0.05). The MUTBS values of
      these materials to dentin were XTR>EVO>SDR (p>0.05). CONCLUSION: Within the
      limitations of this study, the use of a bonding agent without acid-etching showed
      positive interactions between base materials and composite resin and there were
      no significant differences in MUTBS of these materials to dentin.

PMID- 26208070
TI  - Antibacterial Efficacy of Pastes Against E Faecalis in Primary Root Dentin: A
      Confocal Microscope Study.
AB  - OBJECTIVES: Management of abscessed primary teeth often present endodontic
      failure owing to questioned efficiency of dressings or obturating pastes to
      eliminate Enterococcus faecalis, a resistant bacterium, residing in depth of
      dentinal tubules. The present study evaluates the antimicrobial efficacy of two
      antibacterial and two obturating pastes in dentinal tubules of primary teeth
      infected with Enterococcus faecalis using viability stain and confocal laser
      scanning microscope (CLSM). STUDY DESIGN: Total 28 samples were prepared.Four
      groups with 6 samples each were made according to antibacterial pastes i.e. 1% or
      2%Chlorhexidine (CHX) + calcium hydroxide (CH), CH + iodoform (Metapex) and Zinc
      Oxide Eugenol (ZOE). Dentinal tubules from the root canal side were infected with
      E. faecalis by centrifugation of the bacterial suspension. Two specimens from
      each group were subjected to 1, 7 and 15 days antibacterial pastes exposure.
      Viability staining followed by CLSM were used to quantitatively analyze the dead
      cell count directly inside dentin. RESULT: Univariate analysis showed that all
      medicaments were significantly effective (p<.05). Kruskal wallis ANOVA test did
      not show significant difference among four medicaments at day 1 while it was
      significantly different at day 7 & 15. Paired sample student's t-test revealed
      significant difference in efficacy between 1& 15 days for 1%CHX+CH; between
      1&15,and 7&15 days; between all days for ZOE. Ranking of antimicrobial efficacy
      of tested medicament was (most effective to the least): 1%CHX+CH(15)> ZOE(15)>
      Metapex(15)> 2%CHX+CH(15)> 2%CHX+CH(7)> 2%CHX+CH(1)> 1%CHX+CH(7)> 2%CHX+CH(15)>
      Metapex(1)> ZOE(1)> ZOE(7). CONCLUSIONS: All medicaments were effective against
      E. faecalis in dentine of primary teeth and their efficacy increased with longer
      contact with 1%CHX+CH being most effective at day 15. Inclusion of 1% CHX in
      dressings or obturating pastes might minimize the endodontic relapse and maximize
      the tooth retention in functional state in pediatric dentistry.

PMID- 26208071
TI  - Effect of Human Milk and its Components on Streptococcus Mutans Biofilm
      Formation.
AB  - OBJECTIVE: This study investigated the effects of human breast milk and its
      components on the nutritional aspect of the caries process due to Streptococcus
      mutans UA159 biofilm formation. STUDY DESIGN: Human breast milk was collected
      from 11 mothers during 3-9 months postpartum. To test for the effect on biofilm
      formation, a 16-hour culture of S. mutans was treated with dilutions of human
      breast milk and several major components of human breast milk, lactose,
      lactoferrin, IgA, and bovine casein in sterile 96-well flat bottom microtiter
      plates for 24 hours. The biofilms were fixed, washed, stained with crystal
      violet, and extracted. Absorbance was measured to evaluate biofilm growth mass.
      RESULTS: Dilutions 1:10-1:2,560 of the human breast milk samples increased
      biofilm formation by 1.5-3.8 fold compared to the control. Lactoferrin decreased
      biofilm formation significantly in all dilutions (average milk concentration of 3
      mg/ml). Lactose had no effect at average breast milk concentrations (60 mg/ml)
      except at its lowest concentration (15 mg/ml) where it was increased. IgA
      significantly decreased biofilm formation at its highest concentration of 2,400
      MUg/ml (average milk concentration 600 MUg/ml). Casein caused significantly
      increased biofilm formation at all concentrations tested above the average milk
      content (2.3 mg/ml). CONCLUSIONS: The results of this study demonstrate an
      increase in S. mutans biofilm formation by human breast milk 3-9 months post
      partum. Among its major components, only casein significantly increased biofilm
      formation among the concentrations analyzed. Lactose had no effect except at 15
      mg/ml. Lactoferrin and IgA significantly decreased S. mutans biofilm formation at
      their highest concentrations. This information expands the current knowledge
      regarding the nutritional influence of breastfeeding and validates the necessity
      to begin an oral hygiene regimen once the first tooth erupts.

PMID- 26208072
TI  - Maturogenesis of an Early Erupted Immature Permanent Tooth: A Case Report With 7
      Year Follow-Up.
AB  - The main objective of treatment of an undeveloped tooth (immature) is to provide
      vital pulp therapy to allow continued development of root dentin. A case report
      is presented that demonstrates the use of calcium hydroxide (CaOH2) as an
      indirect pulp-copping material for the purpose of continued maturogenesis of an
      early-erupted permanent tooth with severe mobility and almost-begun root
      formation. Seven-year radiographic and clinical follow-up demonstrated a vital
      pulp and physiologic root development without any endodontic failure clinically
      or radiographicaly.

PMID- 26208073
TI  - Large Doses of Propranolol for the Treatment of Infantile Cephalic and Facial
      Hemangiomas: A Clinical Report of 38 Cases.
AB  - OBJECTIVE: Infantile cephalic and facial hemangiomas (IHs) are common and
      histologically benign vascular lesions in infants. This study investigates the
      clinical effect of using large doses of Propranolol for the treatment of IHs.
      STUDY DESIGN: This study contains 38 patients with IHs. All patients received
      general screening before the treatment. The dosage of Propranolol was increased
      over the course of treatment, which initiated three days. 1mg/kg on the first
      day, then increased by 0.5 mg/kg each day. The daily dose was divided into two
      smaller doses, administered every 12 hours, half an hour after feeding. Patients
      were hospitalized for six days. In the absence of side effects, treatment was
      continued at home and patients were reevaluated every month. Generally, one
      course of treatment lasted six months. RESULTS: With the treatment, the entire
      group had significant improvement. 6 of them had excellent results. 22 had a good
      response with considerable lesion reduction. Side effects were limited during or
      after the treatment. CONCLUSIONS: Large doses of oral Propranolol to treat severe
      IHs patients had great clinical results. The treatment can shorten the natural
      course of IHs, making it a possible first choice for treatment.

PMID- 26208074
TI  - Oral Health Survey of 6-14-Year-Old Children with Disabilities Attending Special
      Schools Yemen.
AB  - OBJECTIVES: The purpose of this study was to assess the oral health status and
      treatment needs of children with disabilities attending special schools in
      Sana'a, Yemen. STUDY DESIGN: This cross-sectional study involved 401 children
      with different disabilities aged between 6 and 14 years. Dental caries was
      evaluated using DMFT/dmft indices in accordance with WHO criteria. The plaque
      index (PI) and the gingival index (GI) were used to assess oral hygiene and
      gingival health, respectively. RESULTS: The mean dmft and DMFT scores of the
      total population were 4.27 and 1.90 respectively, with no significant differences
      across gender (p>0.05). According to the type of disability, the physically
      disabled had the highest mean dmft of 4.68 (SD 3.30) and subjects with compound
      disabilities had the highest mean DMFT of 2.85 (SD 1.98). Among the disability
      groups, the blind had the highest PI and GI scores, and the deaf had the lowest.
      Majority of the children were on need for specific type of dental treatment.
      CONCLUSION: This study suggests that children with disabilities have a high
      prevalence of dental caries and poor oral hygiene.

PMID- 26208075
TI  - Oral Health Education Program on Dental Caries Incidence for School Children.
AB  - OBJECTIVE: This 3-year retrospective controlled clinical trial assessed the
      effect of a school-based oral health education program on caries incidence in
      children. STUDY DESIGN: A total of 240 students, aged 5 to 7 years, from two
      public schools in Monte Siao, Brazil, were included in this study. A school-based
      oral health education program was developed in one of the schools (experimental
      group), including 120 students, while the 120 students from the other school did
      not participate in the program (control group). All children were initially
      examined for dental caries (dmf-t), and after 3 years, 98 children from the
      experimental group and 96 from the control group were again examined and answered
      a questionnaire on oral health issues. The between-groups difference in caries
      incidence on permanent teeth was calculated using Poisson regression analyses.
      Logistic regression was used to observe the association between caries incidence
      and other variables. RESULTS: More students from the experimental group stated
      knowing what was dental caries and declared that they use dental floss daily, but
      no significant differences in caries incidence was observed between the
      experimental and control groups. CONCLUSION: The school-based oral health
      education program is not adequately efficient to decrease caries incidence after
      three years, but some issues about oral health knowledge could be slightly
      improved.

PMID- 26208076
TI  - Pediatric Dental Sedation Research: Where Do We Stand Today?
AB  - Despite the voluminous literature addressing the safety and efficacy of various
      sedative agents in the pediatric dental setting, the quality literature to form
      evidence based pediatric dental sedation practice is not available. Our search
      through PUBMED showed that during 1985-2012, a total of 184 original research
      papers on pediatric dental sedation were reported, and midazolam clearly
      dominated with 88 trials on this agent. Despite these large numbers of papers,
      Cochrane Review was able to pool a weak evidence in favor of midazolam. Data
      pooling from five heterogeneous high risk of bias trials showed that oral
      midazolam is associated with more cooperative behavior when compared to a
      placebo. Further, a very weak evidence regarding efficacy of nitrous oxide was
      collected from two trials, which could not be pooled. These findings draw
      attention to the need to address the shortcomings in the current state of
      pediatric dental sedation research. The present article has been focused on the
      current status of pediatric dental sedation research, and the limitations in the
      current research methodology. This paper also suggests recommendations for future
      research in the field of pediatric dental sedation. 

PMID- 26208077
TI  - Management Guidelines for Traumatically Injured Teeth during Orthodontic
      Treatment.
AB  - This article presents a summary of incident management guidelines for
      traumatically injured teeth during orthodontic treatment. In addition, treatment
      of a 17-year-old patient with traumatic extrusion and palatal displacement of the
      permanent maxillary incisors while undergoing active orthodontic treatment is
      reported. 

PMID- 26208078
TI  - Brief report: Executive functions in adolescent offspring of mothers with a
      history of depression.
AB  - Deficits in executive functions (EFs) have been documented among individuals with
      unipolar depression, but controversy exists as to whether such deficits are state
      dependent or are trait markers that precede disorder onset. The present study
      examined whether maternal history of unipolar depression was associated with
      deficits in EFs in early adolescent offspring, a finding that would support a
      trait marker conceptualization of EF deficits. Participants were a diverse sample
      (N = 493) of adolescents and their mothers recruited through local schools.
      Measures included semi-structured diagnostic interviews of mother and adolescent,
      mother-report forms assessing demographic information, and tests of executive
      function. Hierarchical linear regression analyses were conducted to examine the
      association between maternal depression diagnosis and adolescent offspring
      performance on tests of EF. Maternal lifetime history of depression was not
      associated with offspring EF task performance. Findings are not consistent with
      the conceptualization of impaired executive functions as trait markers of
      unipolar depression. 

PMID- 26208079
TI  - Parental attachment and Chinese adolescents' delinquency: The mediating role of
      moral disengagement.
AB  - There is substantial literature documenting the negative association between
      secure parental attachment and lower adolescent delinquency, but little is known
      about the mediating mechanisms (i.e., how does parental attachment relate to
      delinquency?) underlying this relation. The present study examined whether secure
      parental attachment would be indirectly related to lower adolescent delinquency
      through lower adolescent moral disengagement. A total of 1766 adolescents (44%
      male; mean age = 14.25 years, SD = 1.54) living in an urban area of southern
      China completed anonymous questionnaires regarding parental attachment, moral
      disengagement and delinquency. After controlling for gender, age, socioeconomic
      status, and school variable, it was found that secure parental attachment was
      negatively associated with adolescent delinquency and this negative association
      was fully mediated by the extent of adolescent moral disengagement. These
      findings contribute to an understanding of the mechanisms underlying the
      development of adolescent delinquency and have important implications for
      intervention. 

PMID- 26208080
TI  - In Situ Formation of a Biocatalytic Alginate Membrane by Enhanced Concentration
      Polarization.
AB  - A thin alginate layer induced on the surface of a commercial polysulfone membrane
      was used as a matrix for noncovalent immobilization of enzymes. Despite the
      expected decrease of flux across the membrane resulting from the coating, the
      initial hypothesis was that such a system should allow high immobilized enzyme
      loadings, which would benefit from the decreased flux in terms of increased
      enzyme/substrate contact time. The study was performed in a sequential fashion:
      first, the most suitable types of alginate able to induce a very thin,
      sustainable gel layer by pressure-driven membrane filtration were selected and
      evaluated. Then, an efficient method to make the gel layer adhere to the surface
      of the membrane was developed. Finally, and after confirming that the enzyme
      loading could remarkably be enhanced by using this method, several strategies to
      increase the permeate flux were evaluated. Alcohol dehydrogenase (EC 1.1.1.1),
      able to catalyze the conversion of formaldehyde into methanol, was selected as
      the model enzyme. An enzyme loading of 71.4% (44.8 MUg/cm(2)) was attained under
      the optimal immobilization conditions, which resulted in a 40% conversion to
      methanol as compared to the control setup (without alginate) where only 10.8%
      (6.9 MUg/cm(2)) enzyme was loaded, with less than 5% conversion. Such conversion
      increased to 60% when polyethylene glycol (PEG) was added during the construction
      of the gel layer, as a strategy to increase flux. No enzyme leakage was observed
      for both cases (with/without PEG addition). Modeling results showed that the
      dominant fouling mechanism during gel layer induction (involving enzyme
      entrapment) was cake layer formation in the initial and intermediate phases,
      while pore blocking was the dominant mechanism in the final phase. Such
      mechanisms had a direct consequence on the type of immobilization promoted in
      each phase. The results suggested that the strategy proposed could be efficiently
      used to enhance the enzyme loading on polymer membranes. 

PMID- 26208081
TI  - Understanding the connection between self-esteem and aggression: The mediating
      role of emotion dysregulation.
AB  - The purpose of the present study was to extend previous knowledge concerning the
      link between self-esteem and aggression by examining the mediating role of
      emotion dysregulation among offenders and community participants. A sample of 153
      incarcerated violent offenders and a community sample of 197 individuals
      completed self-report measures of self-esteem level, emotion dysregulation, and
      trait aggression. Offenders reported lower levels of self-esteem than community
      participants, as well as greater levels of emotional nonacceptance and hostility.
      Bootstrapping analyses were performed to test whether emotion dysregulation
      mediated the association between self-esteem level and aggression. In the
      offender sample, mediation models were significant for three of the four aspects
      of trait aggression that were considered. Emotion dysregulation fully mediated
      the links that low self-esteem had with physical aggression, anger, and
      hostility. The same pattern (with the addition of full mediation for verbal
      aggression) was confirmed in the community sample. Our findings suggest that
      emotion dysregulation may play an important role in the connection between low
      self-esteem and aggression. Alternative models of the associations among these
      variables were tested and discussed. As a whole, the present results are
      consistent with those of other studies and suggest that it may be beneficial to
      include emotion regulation modules as part of prevention and treatment programs
      for violent offenders.

PMID- 26208082
TI  - NK cell interplay with cytomegaloviruses.
AB  - NK cells play an important role in the control of viral infections.
      Cytomegaloviruses have played a big part in the accumulation of current knowledge
      describing how NK cells recognize and eliminate infected cells. The interference
      with these functions at multiple levels may not only play a role in the control
      of primary infections or reactivations but can also impact other arms of the
      immune system and leave a long-lasting stable imprint on the NK cell population.
      These imprints may, in turn, modify how we respond to other infections.
      Understanding these processes will allow us to design better diagnostic
      approaches and new treatment options through manipulation of our immune responses
      and the viruses themselves. 

PMID- 26208083
TI  - Visual perspective in remembering and episodic future thought.
AB  - According to the constructive episodic simulation hypothesis, remembering and
      episodic future thinking are supported by a common set of constructive processes.
      In the present study, we directly addressed this assertion in the context of
      third-person perspectives that arise during remembering and episodic future
      thought. Specifically, we examined the frequency with which participants
      remembered past events or imagined future events from third-person perspectives.
      We also examined the different viewpoints from which third-person perspective
      events were remembered or imagined. Although future events were somewhat more
      likely to be imagined from a third-person perspective, the spatial viewpoint
      distributions of third-person perspectives characterizing remembered and imagined
      events were highly similar. These results suggest that a similar constructive
      mechanism may be at work when people remember events from a perspective that
      could not have been experienced in the past and when they imagine events from a
      perspective that could not be experienced in the future. The findings are
      discussed in terms of their consistency with--and as extensions of--the
      constructive episodic simulation hypothesis.

PMID- 26208084
TI  - Stance limb kinetics of older male athletes endurance running performance.
AB  - The aim of this study was to examine the age-based, lower limb kinetics of
      running performances of endurance athletes. Six running trials were performed by
      24 male athletes, who were distinguished by three age groupings (S35: 26-32
      years, M50: 50-54 years, M60+: 60-68 years). Lower limb coordinate and ground
      reaction force data were collected using a nine camera infra-red system
      synchronised with a force plate. A slower anteroposterior (M +/- SD S35 = 4.13 +/
      0.54 m/s: M60+ = 3.34 +/- 0.40 m/s, p < 0.05) running velocity was associated
      with significant (p < 0.05) decreases in step length and discrete vertical ground
      contact force between M60+and S35 athletes. The M60+athletes simultaneously
      generated a 32% and 42% reduction (p < 0.05) in ankle joint moment when compared
      to the M50 and S35 athletes and 72% (p < 0.05) reduction in knee joint stiffness
      when compared to S35 athletes. Age-based declines in running performance were
      associated with reduced stance phase force tolerance and generation that may be
      accounted for due to an inhibited force-velocity muscular function of the lower
      limb. Joint-specific coaching strategies customised to athlete age are warranted
      to maintain/enhance athletes' dynamic performance.

PMID- 26208085
TI  - Positive affective tone and team performance: The moderating role of collective
      emotional skills.
AB  - Research on affect as a group-level phenomenon has shown that over time,
      individual members within a group become highly similar in their affect (i.e.,
      members experience and display similar emotions and moods), and often become
      similar enough that the aggregation of individuals' affect can meaningfully
      represent the "affective tone" of the group. It is generally assumed that a more
      positive affective tone will lead to better team performance. We challenge the
      conclusion that positive affective tone is always good for team performance,
      suggesting that the relationship between positive affective tone and team
      performance is subject to moderating influences. Across two studies, we
      demonstrate that the self-reported collective emotional skills of team members
      play a crucial role in determining whether positive affective tone is beneficial
      or detrimental to team performance. Implications for theory and practice are
      discussed. 

PMID- 26208090
TI  - Why and How Limb Muscle Mass and Function Should Be Measured in Patients with
      Chronic Obstructive Pulmonary Disease.
AB  - Impaired limb muscle function is a common occurrence in patients with chronic
      obstructive pulmonary disease (COPD), and it negatively influences exercise
      tolerance, quality of life, and even survival. Assessment of limb muscle mass and
      function in COPD is highly encouraged; it should include the quadriceps muscle,
      but other lower and upper limb muscles may also be evaluated to provide valuable
      information. Quantification of muscle mass as well as assessment of muscle
      strength and endurance are suggested. Bioelectrical impedance and dual-energy X
      ray absorption can be realistically used in the clinical environment to monitor
      body composition. Although sophisticated computerized dynamometers provide the
      most accurate assessment, simple exercise and testing equipment are valid
      alternatives and they should help in implementing limb muscle function assessment
      in clinical settings. Isometric measurements, using strain-gauges or hand-held
      dynamometers, should be favored for their simplicity, availability, and quality
      of information provided. This perspective provides a rationale for the evaluation
      of limb muscle mass and function in COPD in routine clinical practice. In
      addition, measurement techniques used to assess limb muscle mass, strength,
      endurance, and fatigue in various clinical settings are discussed. 

PMID- 26208091
TI  - A new bisabolane-type sesquiterpenoid from the fermentation broth of fungus
      Antrodiella gypsea.
AB  - Studies of the fermentation broth of fungus Antrodiella gypsea led to the
      isolation of a new bisabolane-type sesquiterpenoid that was named gypseatriol
      (1), together with the known compound 2,10-dodecadiene-1,6,7-triol (2). The
      structure of this new metabolite was assigned by analysis of 2D NMR and HR-EI-MS.
      Absolute configuration was assigned by single crystal X-ray diffraction analysis.
      Compound 1 was evaluated for its antifungal activity on Candida albicans. 

PMID- 26208092
TI  - Correlation of In Vivo and Ex Vivo ADC and T2 of In Situ and Invasive Murine
      Mammary Cancers.
AB  - Ex vivo MRI may aid in the evaluation of surgical specimens, and provide valuable
      information regarding the micro-anatomy of mammary/breast cancer. The use of ex
      vivo MRI to study mouse mammary cancer would be enhanced if there is a strong
      correlation between parameters derived from in vivo and ex vivo scans. Here, we
      report the correlation between apparent diffusion coefficient (ADC) and T2 values
      measured in vivo and ex vivo in mouse mammary glands with in situ cancers
      (mammary intraepithelial neoplasia (MIN)) and invasive cancers (those which
      spread outside the ducts into surrounding tissue). MRI experiments were performed
      on the Polyoma middle T oncoprotein breast cancer mouse model (n = 15) in a 9.4T
      scanner. For in vivo experiments, T2-weighted (T2W) images were acquired to
      identify abnormal regions, then ADC and T2 values were measured for nine selected
      slices. For ex vivo experiments, a midline incision was made along the spine, and
      then skin, glands, and tumors were gently peeled from the body. Tissue was fixed
      in formalin, placed around a mouse-sized sponge, and sutured together mimicking
      the geometry of the gland when attached to the mouse. The same pulse sequences
      used for in vivo experiments were repeated for ex vivo scans at room temperature.
      Regions of interest were manually traced on T2W images defining features that
      could be identified on in vivo and ex vivo images. The results demonstrate a
      strong positive correlations between in vivo and ex vivo invasive cancers for ADC
      (r = 0.89, p <0.0001) and T2 (r = 0.89, p <0.0001) values; and weak to moderate
      positive correlations between in vivo and ex vivo in situ cancers for ADC (r =
      0.61, p <0.0001) and T2 (r = 0.79, p <0.0001) values. The average ex vivo ADC
      value was about 54% of the in vivo value; and the average ex vivo T2 was similar
      to the in vivo value for cancers. Although motion, fixation, and temperature
      differences affect ADC and T2, these results show a reliable relationship between
      ADC and T2 in vivo and ex vivo. As a result ex vivo images can provide valuable
      information with clinical and research applications. 

PMID- 26208094
TI  - Correction: Is the Relationship between Common Mental Disorder and Adiposity
      Bidirectional? Prospective Analyses of a UK General Population-Based Study.

PMID- 26208093
TI  - GREAM: A Web Server to Short-List Potentially Important Genomic Repeat Elements
      Based on Over-/Under-Representation in Specific Chromosomal Locations, Such as
      the Gene Neighborhoods, within or across 17 Mammalian Species.
AB  - BACKGROUND: Genome-wide repeat sequences, such as LINEs, SINEs and LTRs share a
      considerable part of the mammalian nuclear genomes. These repeat elements seem to
      be important for multiple functions including the regulation of transcription
      initiation, alternative splicing and DNA methylation. But it is not possible to
      study all repeats and, hence, it would help to short-list before exploring their
      potential functional significance via experimental studies and/or detailed in
      silico analyses. RESULT: We developed the 'Genomic Repeat Element Analyzer for
      Mammals' (GREAM) for analysis, screening and selection of potentially important
      mammalian genomic repeats. This web-server offers many novel utilities. For
      example, this is the only tool that can reveal a categorized list of specific
      types of transposons, retro-transposons and other genome-wide repetitive elements
      that are statistically over-/under-represented in regions around a set of genes,
      such as those expressed differentially in a disease condition. The output
      displays the position and frequency of identified elements within the specified
      regions. In addition, GREAM offers two other types of analyses of genomic repeat
      sequences: a) enrichment within chromosomal region(s) of interest, and b)
      comparative distribution across the neighborhood of orthologous genes. GREAM
      successfully short-listed a repeat element (MER20) known to contain functional
      motifs. In other case studies, we could use GREAM to short-list repetitive
      elements in the azoospermia factor a (AZFa) region of the human Y chromosome and
      those around the genes associated with rat liver injury. GREAM could also
      identify five over-represented repeats around some of the human and mouse
      transcription factor coding genes that had conserved expression patterns across
      the two species. CONCLUSION: GREAM has been developed to provide an impetus to
      research on the role of repetitive sequences in mammalian genomes by offering
      easy selection of more interesting repeats in various contexts/regions. GREAM is
      freely available at http://resource.ibab.ac.in/GREAM/.

PMID- 26208096
TI  - Usefulness of pulsed-field gel electrophoresis profiles for the determination of
      Salmonella serovars.
AB  - We created a database consisting of a large number of Salmonella pulsed-field gel
      electrophoresis (PFGE) profiles covering a wide range of different serovars. This
      database was used for the prediction of the serovars based on the PFGE profiles
      for isolates from Taiwan and Denmark. The PFGE profiles proved very useful in the
      determination of a serovar although serovar prediction was more efficient for
      local isolates than those from a distant geographic area. To use a highly
      stringent band matching tolerance in the BioNumerics software is also important
      for the grouping of serovars. 

PMID- 26208095
TI  - PPARgamma Ligands Attenuate Hypoxia-Induced Proliferation in Human Pulmonary
      Artery Smooth Muscle Cells through Modulation of MicroRNA-21.
AB  - Pulmonary hypertension (PH) is a progressive and often fatal disorder whose
      pathogenesis involves pulmonary artery smooth muscle cell (PASMC) proliferation.
      Although modern PH therapies have significantly improved survival, continued
      progress rests on the discovery of novel therapies and molecular targets.
      MicroRNA (miR)-21 has emerged as an important non-coding RNA that contributes to
      PH pathogenesis by enhancing vascular cell proliferation, however little is known
      about available therapies that modulate its expression. We previously
      demonstrated that peroxisome proliferator-activated receptor gamma (PPARgamma)
      agonists attenuated hypoxia-induced HPASMC proliferation, vascular remodeling and
      PH through pleiotropic actions on multiple targets, including transforming growth
      factor (TGF)-beta1 and phosphatase and tensin homolog deleted on chromosome 10
      (PTEN). PTEN is a validated target of miR-21. We therefore hypothesized that
      antiproliferative effects conferred by PPARgamma activation are mediated through
      inhibition of hypoxia-induced miR-21 expression. Human PASMC monolayers were
      exposed to hypoxia then treated with the PPARgamma agonist, rosiglitazone (RSG,10
      MUM), or in parallel, C57Bl/6J mice were exposed to hypoxia then treated with
      RSG. RSG attenuated hypoxic increases in miR-21 expression in vitro and in vivo
      and abrogated reductions in PTEN and PASMC proliferation. Antiproliferative
      effects of RSG were lost following siRNA-mediated PTEN depletion. Furthermore,
      miR-21 mimic decreased PTEN and stimulated PASMC proliferation, whereas miR-21
      inhibition increased PTEN and attenuated hypoxia-induced HPASMC proliferation.
      Collectively, these results demonstrate that PPARgamma ligands regulate
      proliferative responses to hypoxia by preventing hypoxic increases in miR-21 and
      reductions in PTEN. These findings further clarify molecular mechanisms that
      support targeting PPARgamma to attenuate pathogenic derangements in PH. 

PMID- 26208097
TI  - Effect of Local Basic Fibroblast Growth Factor and Vascular Endothelial Growth
      Factor on Subcutaneously Allotransplanted Ovarian Tissue in Ovariectomized Mice.
AB  - OBJECTIVE: One of the major obstacles to ovarian tissue preservation is delayed
      angiogenesis that leads follicles lost after transplantation. The aim of the
      present study was to investigate the effects of bFGF and VEGF on heterotopic
      transplanted ovarian tissue using a mouse model. METHODS: Female mice underwent
      bilateral ovariectomy. Ovarian tissues encapsulated by fibrin hydrogels were
      transplanted subcutaneously into recipient mice, in which ovarian hormonal
      cyclicity was absent. The fibrinogen solution was mixed with bFGF, VEGF, or a
      mixture of bFGF and VEGF. The grafts were recovered 21 days after
      transplantation. Follicle morphology and follicle numbers were observed by H&E
      staining. Blood vessels were observed in transplanted intra-ovarian tissue by
      CD31 antibody IHC staining. Daily vaginal cytology was performed to determine
      estrous cycle and functional restoration of transplanted ovarian tissue. Blood
      was collected weekly and serum FSH levels were measured with a radioimmunoassay
      kit. Apoptosis analysis was performed by anti-AC-3 staining and survivin mRNA
      expression. RESULTS: The number of primordial follicles and secondary follicles
      in the bFGF+VEGF group was significantly higher than in the control group. The
      vascular density in the bFGF+VEGF groups were significantly higher than in the
      bFGF and the VEGF groups; there was no significant difference between the bFGF
      and VEGF groups. Estrous cycle was earlier in the bFGF+VEGF group compared with
      the control group; all mice in this group restored ovarian function. Serum FSH
      levels in the bFGF+VEGF group were significantly lower than in the control group
      by day 14 post-transplantation. The AC-3-positive in control group was
      significantly higher compared with bFGF group and VEGF group, and in bFGF+VEGF
      group was significantly lower than bFGF group and VEGF group. Survivin mRNA
      expression in bFGF+VEGF group was significantly higher than control group.
      CONCLUSION: The combination of bFGF and VEGF has beneficial effects on follicle
      survival, angiogenesis, and resumption of estrous cycles.

PMID- 26208098
TI  - Seasonally-Dynamic Presence-Only Species Distribution Models for a Cryptic
      Migratory Bat Impacted by Wind Energy Development.
AB  - Understanding seasonal distribution and movement patterns of animals that migrate
      long distances is an essential part of monitoring and conserving their
      populations. Compared to migratory birds and other more conspicuous migrants, we
      know very little about the movement patterns of many migratory bats. Hoary bats
      (Lasiurus cinereus), a cryptic, wide-ranging, long-distance migrant, comprise a
      substantial proportion of the tens to hundreds of thousands of bat fatalities
      estimated to occur each year at wind turbines in North America. We created
      seasonally-dynamic species distribution models (SDMs) from 2,753 museum
      occurrence records collected over five decades in North America to better
      understand the seasonal geographic distributions of hoary bats. We used 5 SDM
      approaches: logistic regression, multivariate adaptive regression splines,
      boosted regression trees, random forest, and maximum entropy and consolidated
      outputs to generate ensemble maps. These maps represent the first formal
      hypotheses for sex- and season-specific hoary bat distributions. Our results
      suggest that North American hoary bats winter in regions with relatively long
      growing seasons where temperatures are moderated by proximity to oceans, and then
      move to the continental interior for the summer. SDMs suggested that hoary bats
      are most broadly distributed in autumn-the season when they are most susceptible
      to mortality from wind turbines; this season contains the greatest overlap
      between potentially suitable habitat and wind energy facilities. Comparing wind
      turbine fatality data to model outputs could test many predictions, such as 'risk
      from turbines is highest in habitats between hoary bat summering and wintering
      grounds'. Although future field studies are needed to validate the SDMs, this
      study generated well-justified and testable hypotheses of hoary bat migration
      patterns and seasonal distribution. 

PMID- 26208099
TI  - Involvement of a Case Manager in Palliative Care Reduces Hospitalisations at the
      End of Life in Cancer Patients; A Mortality Follow-Back Study in Primary Care.
AB  - BACKGROUND: Case managers have been introduced in primary palliative care in the
      Netherlands; these are nurses with expertise in palliative care who offer support
      to patients and informal carers in addition to the care provided by the general
      practitioner (GP) and home-care nurse. OBJECTIVES: To compare cancer patients
      with and without additional support from a case manager on: 1) the patients'
      general characteristics, 2) characteristics of care and support given by the GP,
      3) palliative care outcomes. METHODS: This article is based on questionnaire data
      provided by GPs participating in two different studies: the Sentimelc study (280
      cancer patients) and the Capalca study (167 cancer patients). The Sentimelc study
      is a mortality follow-back study amongst a representative sample of GPs that
      monitors the care provided via GPs to a general population of end-of-life
      patients. Data from 2011 and 2012 were analysed. The Capalca study is a
      prospective study investigating the implementation and outcome of the support
      provided by case managers in primary palliative care. Data were gathered between
      March 2011 and December 2013. RESULTS: The GP is more likely to know the
      preferred place of death (OR 7.06; CI 3.47-14.36), the place of death is more
      likely to be at the home (OR 2.16; CI 1.33-3.51) and less likely to be the
      hospital (OR 0.26; CI 0.13-0.52), and there are fewer hospitalisations in the
      last 30 days of life (none: OR 1.99; CI 1.12-3.56 and one: OR 0.54; CI 0.30
      0.96), when cancer patients receive additional support from a case manager
      compared with patients receiving the standard GP care. CONCLUSIONS: Involvement
      of a case manager has added value in addition to palliative care provided by the
      GP, even though the role of the case manager is 'only' advisory and he or she
      does not provide hands-on care or prescribe medication.

PMID- 26208100
TI  - Detection of Nonverbal Synchronization through Phase Difference in Human
      Communication.
AB  - Nonverbal communication is an important factor in human communication, and body
      movement synchronization in particular is an important part of nonverbal
      communication. Some researchers have analyzed body movement synchronization by
      focusing on changes in the amplitude of body movements. However, the definition
      of "body movement synchronization" is still unclear. From a theoretical
      viewpoint, phase difference is the most important factor in synchronization
      analysis. Therefore, there is a need to measure the synchronization of body
      movements using phase difference. The purpose of this study was to provide a
      quantitative definition of the phase difference distribution for detecting body
      movement synchronization in human communication. The phase difference
      distribution was characterized using four statistical measurements: density, mean
      phase difference, standard deviation (SD) and kurtosis. To confirm the
      effectiveness of our definition, we applied it to human communication in which
      the roles of speaker and listener were defined. Specifically, we examined the
      difference in the phase difference distribution between two different
      communication situations: face-to-face communication with visual interaction and
      remote communication with unidirectional visual perception. Participant pairs
      performed a task supposing lecture in the face-to-face communication condition
      and in the remote communication condition via television. Throughout the lecture
      task, we extracted a set of phase differences from the time-series data of the
      acceleration norm of head nodding motions between two participants. Statistical
      analyses of the phase difference distribution revealed the characteristics of
      head nodding synchronization. Although the mean phase differences in synchronized
      head nods did not differ significantly between the conditions, there were
      significant differences in the densities, the SDs and the kurtoses of the phase
      difference distributions of synchronized head nods. These results show the
      difference in nonverbal synchronization between different communication types.
      Our study indicates that the phase difference distribution is useful in detecting
      nonverbal synchronization in various human communication situations. 

PMID- 26208101
TI  - Suramin Inhibits Chikungunya Virus Entry and Transmission.
AB  - The mosquito-borne Chikungunya virus (CHIKV) is a profound global threat due to
      its high rate of contagion and the lack of vaccine or effective treatment.
      Suramin is a symmetric polyanionic naphthylurea that is widely used in the
      clinical treatment of parasite infections. Numerous studies have reported the
      broad antiviral activities of suramin; however, inhibition effects against CHIKV
      have not yet been demonstrated. The aim of this study was thus to investigate the
      antiviral effect of suramin on CHIKV infection and to elucidate the molecular
      mechanism underlying inhibition using plaque reduction assay, RT-qPCR, western
      blot analysis, and plaque assay. Microneutralization assay was used to determine
      the EC50 of suramin in the CHIKV-S27 strain as well as in three other clinical
      strains (0611aTw, 0810bTw and 0706aTw). Time-of-addition was used to reveal the
      anti-CHIKV mechanism of suramin. We also evaluated anti-CHIKV activity with
      regard to viral entry, virus release, and cell-to-cell transmission. Cytopathic
      effect, viral RNA, viral protein, and the virus yield of CHIKV infection were
      shown to diminish in the presence of suramin in a dose-dependent manner. Suramin
      was also shown the inhibitory activities of the three clinical isolates. Suramin
      inhibited the early progression of CHIKV infection, due perhaps to interference
      with virus fusion and binding, which subsequently prevented viral entry. Results
      of a molecular docking simulation indicate that suramin may embed within the
      cavity of the E1/E2 heterodimer to interfere with their function. Suramin was
      also shown to reduce viral release and cell-to-cell transmission of CHIKV. In
      conclusion, Suramin shows considerable potential as a novel anti-CHIKV agent
      targeting viral entry, extracellular transmission, and cell-to-cell transmission.

PMID- 26208102
TI  - Deficiency in Aryl Hydrocarbon Receptor (AHR) Expression throughout Aging Alters
      Gene Expression Profiles in Murine Long-Term Hematopoietic Stem Cells.
AB  - Dysregulation of hematopoietic stem cell (HSC) signaling can contribute to the
      development of diseases of the blood system. Lack of aryl hydrocarbon receptor
      (AhR) has been associated with alterations in gene expression related to HSC
      function and the subsequent development of a myeloproliferative disorder in aging
      female mice. We sorted the most primitive population of HSCs with the highest
      stem cell potential (Long-term, or LT-HSCs) from 18-month-old AhR-null-allele
      (AhR-KO) and WT mice and analyzed gene expression using microarray to determine
      alterations in gene expression and cell signaling networks in HSCs that could
      potentially contribute to the aging phenotype of AhR-KO mice. Comparisons with
      previous array data from 8-week old mice indicated that aging alone is sufficient
      to alter gene expression. In addition, a significant number of gene expression
      differences were observed in aged LT-HSCs that are dependent on both aging and
      lack of AhR. Pathway analysis of these genes revealed networks related to
      hematopoietic stem cell activity or function. qPCR was used to confirm the
      differential expression of a subset of these genes, focusing on genes that may
      represent novel AhR targets due to the presence of a putative AhR binding site in
      their upstream regulatory region. We verified differential expression of PDGF-D,
      Smo, Wdfy1, Zbtb37 and Zfp382. Pathway analysis of this subset of genes revealed
      overlap between cellular functions of the novel AhR targets and AhR itself.
      Lentiviral-mediated knockdown of AhR in lineage-negative hematopoietic cells was
      sufficient to induce changes in all five of the candidate AhR targets identified.
      Taken together, these data suggest a role for AhR in HSC functional regulation,
      and identify novel HSC AhR target genes that may contribute to the phenotypes
      observed in AhR-KO mice. 

PMID- 26208103
TI  - Serum Uric Acid and Renal Transplantation Outcomes: At Least 3-Year Post
      transplant Retrospective Multivariate Analysis.
AB  - Since the association of serum uric acid and kidney transplant graft outcome
      remains disputable, we sought to evaluate the predictive value of uric acid level
      for graft survival/function and the factors could affect uric acid as time
      varies. A consecutive cohort of five hundred and seventy three recipients
      transplanted during January 2008 to December 2011 were recruited. Data and
      laboratory values of our interest were collected at 1, 3, 6, 12, 24 and 36 months
      post-transplant for analysis. Cox proportional hazard model, and multiple
      regression equation were built to adjust for the possible confounding variables
      and meet our goals as appropriate. The current cohort study lasts for 41.86 +/-
      15.49 months. Uric acid level is proven to be negatively associated with eGFR at
      different time point after adjustment for age, body mass index and male gender
      (standardized beta ranges from -0.15 to -0.30 with all P<0.001).Males with low
      eGFR but high level of TG were on CSA, diuretics and RAS inhibitors and
      experienced at least one episode of acute rejection and diabetic issue were
      associated with a higher mean uric acid level. Hyperuricemia was significantly an
      independent predictor of pure graft failure (hazard ratio=4.01, 95% CI: 1.25
      12.91, P=0.02) after adjustment. But it was no longer an independent risk factor
      for graft loss after adjustment. Interestingly, higher triglyceride level can
      make incidence of graft loss (hazard ratio=1.442, for each unit increase
      millimoles per liter 95% CI: 1.008-2.061, P=0.045) and death (hazard ratio=1.717,
      95% CI: 1.105-2.665, P=0.016) more likely. The results of our study suggest that
      post-transplant elevated serum uric acid level is an independent predictor of
      long-term graft survival and graft function. Together with the high TG level
      impact on poor outcomes, further investigations for therapeutic effect are
      needed. 

PMID- 26208104
TI  - Comparison of Bile Acids and Acetaminophen Protein Adducts in Children and
      Adolescents with Acetaminophen Toxicity.
AB  - Metabolomics approaches have enabled the study of new mechanisms of liver injury
      in experimental models of drug toxicity. Disruption of bile acid homeostasis is a
      known mechanism of drug induced liver injury. The relationship of individual bile
      acids to indicators of oxidative drug metabolism (acetaminophen protein adducts)
      and liver injury was examined in children with acetaminophen overdose,
      hospitalized children with low dose exposure to acetaminophen, and children with
      no recent exposure to acetaminophen. Nine bile acids were quantified through
      targeted metabolomic analysis in the serum samples of the three groups. Bile
      acids were compared to serum levels of acetaminophen protein adducts and alanine
      aminotransferase. Glycodeoxycholic acid, taurodeoxycholic acid, and
      glycochenodeoxycholic acid were significantly increased in children with
      acetaminophen overdose compared to healthy controls. Among patients with
      acetaminophen overdose, bile acids were higher in subjects with acetaminophen
      protein adduct values > 1.0 nmol/mL and modest correlations were noted for three
      bile acids and acetaminophen protein adducts as follows: taurodeoxycholic acid
      (R=0.604; p<0.001), glycodeoxycholic acid (R=0.581; p<0.001), and
      glycochenodeoxycholic acid (R=0.571; p<0.001). Variability in bile acids was
      greater among hospitalized children receiving low doses of acetaminophen than in
      healthy children with no recent acetaminophen exposure. Compared to bile acids,
      acetaminophen protein adducts more accurately discriminated among children with
      acetaminophen overdose, children with low dose exposure to acetaminophen, and
      healthy control subjects. In children with acetaminophen overdose, elevations of
      conjugated bile acids were associated with specific indicators of acetaminophen
      metabolism and non-specific indicators of liver injury. 

PMID- 26208106
TI  - Cross-sectional structural variation relative to midshaft along hominine
      diaphyses. I. The forelimb.
AB  - OBJECTIVES: Analyses of hominine forelimb diaphyseal structure typically employ
      sections located at midshaft. This study addresses three questions. First, how
      accurately must midshaft be defined to yield comparable data? Second, does
      variation in midshaft location due to alternative definitions fall within error
      ranges such that data gathered using different length measurements are
      comparable? Third, do error ranges and length metric effects differ between
      elements or taxa such that certain bones or species are more prone to issues of
      comparability? MATERIALS AND METHODS: Humeri, radii, and ulnae of Homo, Pan, and
      Gorilla were CT-scanned at full length and error ranges for three structural
      parameters (CSA, J, Imax /Imin ) were calculated around midshafts. RESULTS:
      Distances proximally and distally from midshaft where structural values become
      significantly different from midshaft values vary between elements, taxa, and
      structural parameters. Error ranges are largest for the humerus and smallest for
      the ulna. Among taxa, error ranges for gorillas are largest and those for humans
      are smallest. Among structural parameters, error ranges depend on element and
      taxon such that no parameter consistently exhibits larger or smaller error ranges
      across all bones or species. Variation in midshaft locations originating from
      different length definitions is small and falls within error ranges defined by
      maximum length across all elements and taxa. DISCUSSION: Including fragmentary
      specimens for which midshaft location is uncertain in comparisons of forelimb
      diaphyseal structure requires evaluation on a case-by-case basis, with
      consideration to element, taxon, and structural traits of interest. However,
      midshaft data for all three structural parameters considered here that are
      recorded using different length measurements can be reasonably compared.

PMID- 26208105
TI  - Is Availability of Mammography Services at Federally Qualified Health Centers
      Associated with Breast Cancer Mortality-to-Incidence Ratios? An Ecological
      Analysis.
AB  - OBJECTIVE: Mammography is the most effective method to detect breast cancer in
      its earliest stages, reducing the risk of breast cancer death. We investigated
      the relationship between accessibility of mammography services at Federally
      Qualified Health Centers (FQHCs) and mortality-to-incidence ratio (MIR) of breast
      cancer in each county in the United States. METHODS: County-level breast cancer
      mortality and incidence rates in 2006-2010 were used to estimate MIRs. We
      compared breast cancer MIRs based on the density and availability of FQHC
      delivery sites with or without mammography services both in the county and in the
      neighboring counties. RESULTS: The relationship between breast cancer MIRs and
      access to mammography services at FQHCs differed by race and county of residence.
      Breast cancer MIRs were lower in counties with mammography facilities or FQHC
      delivery sites than in counties without a mammography facility or FQHC delivery
      site. This trend was stronger in urban counties (p=0.01) and among whites
      (p=0.008). Counties with a high density of mammography facilities had lower
      breast cancer MIRs than other counties, specifically in urban counties (p=0.01)
      and among whites (p=0.01). Breast cancer MIR for blacks was the lowest in
      counties having mammography facilities; and was highest in counties without a
      mammography facility within the county or the neighboring counties (p=0.03).
      CONCLUSIONS: Mammography services provided at FQHCs may have a positive impact on
      breast cancer MIRs. Expansion of services provided at the FQHCs and placement of
      FQHCs in additional underserved areas might help to reduce cancer disparities in
      the United States.

PMID- 26208107
TI  - Correction: Segmentation and Classification of Bone Marrow Cells Images Using
      Contextual Information for Medical Diagnosis of Acute Leukemias.

PMID- 26208108
TI  - Probable RBD and association with neurodegenerative disease markers: A population
      based study.
AB  - BACKGROUND: The prevalence of rapid eye movement sleep behavior disorder (RBD)
      and its association with markers of neurodegeneration in the general population
      are poorly defined. METHODS: We assessed the prevalence of probable RBD defined
      by two validated questionnaires, the RBD Screening Questionnaire (RBDSQ) and the
      Innsbruck RBD-Inventory (RBD-I), and studied its associations with clinical and
      imaging markers for neurodegeneration in the Bruneck Study cohort aged 60 y or
      older. RESULTS: Of the 456 participants without Parkinson's disease, 4.6% (RBDSQ;
      95%CI, 3.0%-7.0%) and 7.7% (RBD-I; 95%CI, 5.6%-10.5%) had probable RBD. Probable
      RBD diagnosed with either of the questionnaires was associated with hyposmia
      (trend; P < 0.1), anxiety (P < 0.05), depression (P < 0.05), antidepressant use
      (P < 0.05), and self-reported non-motor symptoms (P < 0.01), specifically,
      dribbling saliva, memory problems, apathy, concentration problems, and anxiety.
      CONCLUSIONS: Our findings may provide a basis for future studies intending to
      identify cohorts at risk for Lewy body diseases through screening of the general
      elderly population for RBD.

PMID- 26208110
TI  - Influence of cathode on the electro-generation of peroxydisulfuric acid oxidant
      and its application for effective removal of SO2 by room temperature electro
      scrubbing process.
AB  - Peroxydisulfuric acid oxidant (H2S2O8) was electro-generated using boron doped
      diamond (BDD) anode in an undivided electrolytic cell under the optimized
      conditions and used for the oxidative removal of gaseous SO2. The influence of
      the nature of cathode material on the formation yield of H2S2O8 was investigated
      with Ti, Pt, Zr and DSA electrodes in a flow type electrolytic cell under batch
      recirculation mode. Among the various cathodes employed Ti exhibited a good
      performance and the formation yield was nearly doubled (0.19 M) compared to the
      reported value of 0.07 M. The optimization of electrode area ratio between the
      anode and cathode brought out the fact that for nearly 8 times smaller Ti cathode
      (8.75:1) the achieved yield was ~65% higher than the 1:1 ratio of anode and
      cathode. The highest concentration of 6.8% (0.48 M) H2S2O8 was seen for 35 cm(2)
      BDD anode with 4 cm(2) Ti at 20  degrees C with the measured redox potential
      value of +1200 mV. The oxidative removal of SO2 in an electro-scrubbing column
      attached to the online production of peroxydisulfuric acid under the optimized
      conditions of cell parameters shows that SO2 removal efficiency was nearly 100%
      for 25 and 50 ppm inlet concentrations and 96% for 100 ppm at the room
      temperature of 25  degrees C.

PMID- 26208111
TI  - Algorithm for the Time-Propagation of the Radial Diffusion Equation Based on a
      Gaussian Quadrature.
AB  - The numerical integration of the time-dependent spherically-symmetric radial
      diffusion equation from a point source is considered. The flux through the source
      can vary in time, possibly stochastically based on the concentration produced by
      the source itself. Fick's one-dimensional diffusion equation is integrated over a
      time interval by considering a source term and a propagation term. The source
      term adds new particles during the time interval, while the propagation term
      diffuses the concentration profile of the previous time step. The integral in the
      propagation term is evaluated numerically using a combination of a new diffusion
      specific Gaussian quadrature and interpolation on a diffusion-specific grid. This
      attempts to balance accuracy with the least number of points for both integration
      and interpolation. The theory can also be extended to include a simple reaction
      diffusion equation in the limit of high buffer concentrations. The method is
      unconditionally stable. In fact, not only does it converge for any time step
      Deltat, the method offers one advantage over other methods because Deltat can be
      arbitrarily large; it is solely defined by the timescale on which the flux source
      turns on and off. 

PMID- 26208109
TI  - Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis
      Associated Immune Reconstitution Inflammatory Syndrome.
AB  - BACKGROUND: Tuberculosis-associated immune reconstitution inflammatory syndrome
      (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients
      receiving antiretroviral therapy (ART). The role of disturbed T cell
      reconstitution in TB-IRIS is not well understood. We investigated T cell
      activation and maturation profiles in patients who developed TB-IRIS at different
      intervals during ART. METHODS: Twenty-two HIV-TB patients who developed early
      onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex
      and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS.
      Flow cytometry analysis was performed on fresh blood, drawn before and after ART
      initiation and during TB-IRIS events. T cell activation and maturation was
      measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27
      antibodies. RESULTS: CD8+ T cell activation before ART was decreased in both
      early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB
      IRIS patients compared to non-IRIS controls. After ART initiation, the observed
      differences in T cell activation disappeared. During late-onset, but not early
      onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and
      CD8+ T cell populations (p<=0.028). CONCLUSION: Our data provide evidence of
      reduced CD8+ T cell activation before ART as a common predisposing factor of
      early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by
      an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was
      characterized by a more terminally differentiated T cell phenotype.

PMID- 26208112
TI  - Multimorbidity Patterns in Hospitalized Older Patients: Associations among
      Chronic Diseases and Geriatric Syndromes.
AB  - BACKGROUND/OBJECTIVES: The clinical status of older individuals with
      multimorbidity can be further complicated by concomitant geriatric syndromes.
      This study explores multimorbidity patterns, encompassing both chronic diseases
      and geriatric syndromes, in geriatric patients attended in an acute hospital
      setting. DESIGN: Retrospective observational study. SETTING: Unit of Social and
      Clinical Assessment (UVSS), Miguel Servet University Hospital (HUMS), Zaragoza
      (Spain). Year, 2011. PARTICIPANTS: A total of 924 hospitalized patients aged 65
      years or older. MEASUREMENTS: Data on patients' clinical, functional, cognitive
      and social statuses were gathered through comprehensive geriatric assessments. To
      identify diseases and/or geriatric syndromes that cluster into patterns, an
      exploratory factor analysis was applied, stratifying by sex. The factors can be
      interpreted as multimorbidity patterns, i.e., diseases non-randomly associated
      with each other within the study population. The resulting patterns were
      clinically assessed by several physicians. RESULTS: The mean age of the study
      population was 82.1 years (SD 7.2). Multimorbidity burden was lower in men under
      80 years, but increased in those over 80. Immobility, urinary incontinence,
      hypertension, falls, dementia, cognitive decline, diabetes and arrhythmia were
      among the 10 most frequent health problems in both sexes, with prevalence rates
      above 20%. Four multimorbidity patterns were identified that were present in both
      sexes: Cardiovascular, Induced Dependency, Falls and Osteoarticular. The number
      of conditions comprising these patterns was similar in men and women. CONCLUSION:
      The existence of specific multimorbidity patterns in geriatric patients, such as
      the Induced Dependency and Falls patterns, may facilitate the early detection of
      vulnerability to stressors, thus helping to avoid negative health outcomes such
      as functional disability.

PMID- 26208113
TI  - The Association of Geographic Coordinates with Mortality in People with Lower and
      Higher Education and with Mortality Inequalities in Spain.
AB  - OBJECTIVE: Geographic patterns in total mortality and in mortality by cause of
      death are widely known to exist in many countries. However, the geographic
      pattern of inequalities in mortality within these countries is unknown. This
      study shows mathematically and graphically the geographic pattern of mortality
      inequalities by education in Spain. METHODS: Data are from a nation-wide
      prospective study covering all persons living in Spain's 50 provinces in 2001.
      Individuals were classified in a cohort of subjects with low education and in
      another cohort of subjects with high education. Age- and sex-adjusted mortality
      rate from all causes and from leading causes of death in each cohort and
      mortality rate ratios in the low versus high education cohort were estimated by
      geographic coordinates and province. RESULTS: Latitude but not longitude was
      related to mortality. In subjects with low education, latitude had a U-shaped
      relation to mortality. In those with high education, mortality from all causes,
      and from cardiovascular, respiratory and digestive diseases decreased with
      increasing latitude, whereas cancer mortality increased. The mortality-rate ratio
      for all-cause death was 1.27 in the southern latitudes, 1.14 in the intermediate
      latitudes, and 1.20 in the northern latitudes. The mortality rate ratios for the
      leading causes of death were also higher in the lower and upper latitudes than in
      the intermediate latitudes. The geographic pattern of the mortality rate ratios
      is similar to that of the mortality rate in the low-education cohort: the highest
      magnitude is observed in the southern provinces, intermediate magnitudes in the
      provinces of the north and those of the Mediterranean east coast, and the lowest
      magnitude in the central provinces and those in the south of the Western
      Pyrenees. CONCLUSION: Mortality inequalities by education in Spain are higher in
      the south and north of the country and lower in the large region making up the
      central plateau. This geographic pattern is similar to that observed in mortality
      in the low-education cohort.

PMID- 26208114
TI  - Inferring Phytoplankton, Terrestrial Plant and Bacteria Bulk delta13C Values from
      Compound Specific Analyses of Lipids and Fatty Acids.
AB  - Stable isotope mixing models in aquatic ecology require delta13C values for food
      web end members such as phytoplankton and bacteria, however it is rarely possible
      to measure these directly. Hence there is a critical need for improved methods
      for estimating the delta13C ratios of phytoplankton, bacteria and terrestrial
      detritus from within mixed seston. We determined the delta13C values of lipids,
      phospholipids and biomarker fatty acids and used these to calculate isotopic
      differences compared to the whole-cell delta13C values for eight phytoplankton
      classes, five bacterial taxa, and three types of terrestrial organic matter (two
      trees and one grass). The lipid content was higher amongst the phytoplankton
      (9.5+/-4.0%) than bacteria (7.3+/-0.8%) or terrestrial matter (3.9+/-1.7%). Our
      measurements revealed that the delta13C values of lipids followed phylogenetic
      classification among phytoplankton (78.2% of variance was explained by class),
      bacteria and terrestrial matter, and there was a strong correlation between the
      delta13C values of total lipids, phospholipids and individual fatty acids.
      Amongst the phytoplankton, the isotopic difference between biomarker fatty acids
      and bulk biomass averaged -10.7+/-1.10/00 for Chlorophyceae and Cyanophyceae, and
      -6.1+/-1.70/00 for Cryptophyceae, Chrysophyceae and Diatomophyceae. For
      heterotrophic bacteria and for type I and type II methane-oxidizing bacteria our
      results showed a -1.3+/-1.30/00, -8.0+/-4.40/00, and -3.4+/-1.40/00 delta13C
      difference, respectively, between biomarker fatty acids and bulk biomass. For
      terrestrial matter the isotopic difference averaged -6.6+/-1.20/00. Based on
      these results, the delta13C values of total lipids and biomarker fatty acids can
      be used to determine the delta13C values of bulk phytoplankton, bacteria or
      terrestrial matter with +/- 1.40/00 uncertainty (i.e., the pooled SD of the
      isotopic difference for all samples). We conclude that when compound-specific
      stable isotope analyses become more widely available, the determination of
      delta13C values for selected biomarker fatty acids coupled with established
      isotopic differences, offers a promising way to determine taxa-specific bulk
      delta13C values for the phytoplankton, bacteria, and terrestrial detritus
      embedded within mixed seston. 

PMID- 26208115
TI  - Melittin Aggregation in Aqueous Solutions: Insight from Molecular Dynamics
      Simulations.
AB  - Melittin is a natural peptide that aggregates in aqueous solutions with
      paradigmatic monomer-to-tetramer and coil-to-helix transitions. Since little is
      known about the molecular mechanisms of melittin aggregation in solution, we
      simulated its self-aggregation process under various conditions. After confirming
      the stability of a melittin tetramer in solution, we observed-for the first time
      in atomistic detail-that four separated melittin monomers aggregate into a
      tetramer. Our simulated dependence of melittin aggregation on peptide
      concentration, temperature, and ionic strength is in good agreement with prior
      experiments. We propose that melittin mainly self-aggregates via a mechanism
      involving the sequential addition of monomers, which is supported by both
      qualitative and quantitative evidence obtained from unbiased and metadynamics
      simulations. Moreover, by combining computer simulations and a theory of the
      electrical double layer, we provide evidence to suggest why melittin aggregation
      in solution likely stops at the tetramer, rather than forming higher-order
      oligomers. Overall, our study not only explains prior experimental results at the
      molecular level but also provides quantitative mechanistic information that may
      guide the engineering of melittin for higher efficacy and safety.

PMID- 26208116
TI  - Clinical Outcomes of In Vitro Fertilization among Chinese Infertile Couples
      Treated for Syphilis Infection.
AB  - To compare the clinical outcomes of infertile patients with and without syphilis
      after in vitro fertilization and embryo transfer (IVF-ET), in this case-control
      study, 320 infertile couples were enrolled and divided into syphilis (n = 160)
      and control groups (n = 160). The primary IVF outcomes were the clinical
      pregnancy rate and the birth of a healthy baby. All syphilis patients received
      the standard anti-syphilis treatment before undergoing IVF/ICSI. Our results
      showed that the endometrial thickness of the syphilis group was greater than that
      of the control group following hCG injection (16.9+/-5.4 vs. 13.0+/-4.7 mm,
      P<0.001). The numbers of normally fertilized eggs and normally cleaved fertilized
      eggs and the implantation rate were 6.8+/-4.8, 6.3+/-4.7 and 24.2%, respectively,
      for the syphilis group and 8.3+/-4.6, 8.1+/-4.6 and 34.4%, respectively, for the
      control group, and these values were significantly different between the groups.
      The clinical pregnancy rate was lower in the syphilis group compared with that in
      the control group (43.8% vs. 55.6%, P = 0.03). Lower offspring birth weight was
      observed in the infected male group compared with those in the infected female
      (2.7+/-0.4 vs. 3.0+/-0.4 kg, P = 0.01) and infected couple groups (2.7+/-0.4 vs.
      3.1+/-0.5 kg, P = 0.007). Therefore, syphilis infection reduces the clinical
      pregnancy rate after IVF/ICSI. 

PMID- 26208117
TI  - Type 2 Diabetes Research Yield, 1951-2012: Bibliometrics Analysis and Density
      Equalizing Mapping.
AB  - The objective of this paper is to provide a detailed evaluation of type 2
      diabetes mellitus research output from 1951-2012, using large-scale data
      analysis, bibliometric indicators and density-equalizing mapping. Data were
      retrieved from the Science Citation Index Expanded database, one of the seven
      curated databases within Web of Science. Using Boolean operators "OR", "AND" and
      "NOT", a search strategy was developed to estimate the total number of published
      items. Only studies with an English abstract were eligible. Type 1 diabetes and
      gestational diabetes items were excluded. Specific software developed for the
      database analysed the data. Information including titles, authors' affiliations
      and publication years were extracted from all files and exported to excel.
      Density-equalizing mapping was conducted as described by Groenberg-Kloft et al,
      2008. A total of 24,783 items were published and cited 476,002 times. The
      greatest number of outputs were published in 2010 (n=2,139). The United States
      contributed 28.8% to the overall output, followed by the United Kingdom (8.2%)
      and Japan (7.7%). Bilateral cooperation was most common between the United States
      and United Kingdom (n=237). Harvard University produced 2% of all publications,
      followed by the University of California (1.1%). The leading journals were
      Diabetes, Diabetologia and Diabetes Care and they contributed 9.3%, 7.3% and 4.0%
      of the research yield, respectively. In conclusion, the volume of research is
      rising in parallel with the increasing global burden of disease due to type 2
      diabetes mellitus. Bibliometrics analysis provides useful information to
      scientists and funding agencies involved in the development and implementation of
      research strategies to address global health issues. 

PMID- 26208118
TI  - Correction of Inverted Nipple Using Subcutaneous Turn-Over Flaps to Create a Tent
      Suspension-Like Effect.
AB  - BACKGROUND: Many techniques have been reported for the correction of inverted
      nipples. However, the conventional methods may be insufficient, especially for
      moderate to severe inversions. We propose a modification of Elsahy's method and
      report satisfactory results. METHODS: A single-institutional retrospective review
      was performed for all patients who received the modified operation. Patient
      charts were reviewed for demographic data, pertinent preoperative factors such as
      Han and Hong classification, and clinical outcomes including postoperative nipple
      height and sensation. Surgical details are described within the main text.
      RESULTS: The review identified 26 female patients amongst whom 47 inverted
      nipples were corrected using the modified method. The mean nipple height was 9 mm
      with an average follow-up period of 14 months. Brush stimulation elicited nipple
      contraction in all patients. There was no recurrence of nipple inversion, nor
      were there any surgical complications to report. CONCLUSION: The suspension
      technique is a simple, reliable method for correcting grade II and III nipple
      inversions.

PMID- 26208119
TI  - Systematic Abeta Analysis in Drosophila Reveals High Toxicity for the 1-42, 3-42
      and 11-42 Peptides, and Emphasizes N- and C-Terminal Residues.
AB  - Brain amyloid plaques are a hallmark of Alzheimer's disease (AD), and primarily
      consist of aggregated Abeta peptides. While Abeta 1-40 and Abeta 1-42 are the
      most abundant, a number of other Abeta peptides have also been identified.
      Studies have indicated differential toxicity for these various Abeta peptides,
      but in vivo toxicity has not been systematically tested. To address this issue,
      we generated improved transgenic Drosophila UAS strains expressing 11 pertinent
      Abeta peptides. UAS transgenic flies were generated by identical chromosomal
      insertion, hence removing any transgenic position effects, and crossed to a novel
      and robust Gal4 driver line. Using this improved Gal4/UAS set-up, survival and
      activity assays revealed that Abeta 1-42 severely shortens lifespan and reduces
      activity. N-terminal truncated peptides were quite toxic, with 3-42 similar to 1
      42, while 11-42 showed a pronounced but less severe phenotype. N-terminal
      mutations in 3-42 (E3A) or 11-42 (E11A) resulted in reduced toxicity for 11-42,
      and reduced aggregation for both variants. Strikingly, C-terminal truncation of
      Abeta (1-41, -40, -39, -38, -37) were non-toxic. In contrast, C-terminal
      extension to 1-43 resulted in reduced lifespan and activity, but not to the same
      extent as 1-42. Mutating residue 42 in 1-42 (A42D, A42R and A42W) greatly reduced
      Abeta accumulation and toxicity. Histological and biochemical analysis revealed
      strong correlation between in vivo toxicity and brain Abeta aggregate load, as
      well as amount of insoluble Abeta. This systematic Drosophila in vivo and in
      vitro analysis reveals crucial N- and C-terminal specificity for Abeta
      neurotoxicity and aggregation, and underscores the importance of residues 1-10
      and E11, as well as a pivotal role of A42. 

PMID- 26208120
TI  - Group cognitive remediation for schizophrenia: Exploring the role of therapist
      support and metacognition.
AB  - OBJECTIVES: Cognitive remediation (CR) is a therapy targeting cognitive
      difficulties in psychiatric disorders. We recently develop a novel CR program for
      people with psychosis with a focus on metacognitive skills individually supported
      by a therapist. This study aims to assess the acceptability and feasibility of
      implementing CR in small groups where therapist support is shared amongst service
      users. DESIGN: Control group design with non-randomized group allocation. METHOD:
      Twenty-five service users with a diagnosis of schizophrenia participated. Ten
      received group CR and 15 individual CR (i.e., one therapist for each service
      user). Both therapy formats were supported by one therapist. Participants were
      assessed before and after therapy with neuropsychological tests assessing
      different cognitive domains, self-assessed cognitive complaints, and psychotic
      symptoms. Treatment satisfaction questionnaires and therapist's session ratings
      were also collected for group CR. RESULTS: Dropout rate was 20% for both methods.
      Session attendance was 74% for group CR and 86% for individual CR. Service users
      evaluated positively group CR and considered it helpful; therapists rated this
      delivery format feasible. Exploratory analysis suggested that the two methods
      have similar effects on cognition. After therapy, service users showed
      improvements in recall memory, reduced negative symptoms, and reported fewer
      cognitive complains. CONCLUSIONS: It is feasible and acceptable for people with
      schizophrenia to take part in small CR therapy groups. The reduced therapist
      contact compared to individual therapy was well tolerated and may help sustain
      independent work. The small group format allows therapists to spend sufficient
      time to support the use of metacognitive strategies. PRACTITIONER POINTS: CR
      small groups are feasible and acceptable for service users and therapists.
      Therapist support can be shared. Metacognitive-based CR can improve cognition and
      may benefit awareness and negative symptoms.

PMID- 26208121
TI  - Two-Dimensional, Ordered, Double Transition Metals Carbides (MXenes).
AB  - The higher the chemical diversity and structural complexity of two-dimensional
      (2D) materials, the higher the likelihood they possess unique and useful
      properties. Herein, density functional theory (DFT) is used to predict the
      existence of two new families of 2D ordered, carbides (MXenes), M'2M"C2 and
      M'2M"2C3, where M' and M" are two different early transition metals. In these
      solids, M' layers sandwich M" carbide layers. By synthesizing Mo2TiC2Tx,
      Mo2Ti2C3Tx, and Cr2TiC2Tx (where T is a surface termination), we validated the
      DFT predictions. Since the Mo and Cr atoms are on the outside, they control the
      2D flakes' chemical and electrochemical properties. The latter was proven by
      showing quite different electrochemical behavior of Mo2TiC2Tx and Ti3C2Tx. This
      work further expands the family of 2D materials, offering additional choices of
      structures, chemistries, and ultimately useful properties. 

PMID- 26208122
TI  - Tinnitus treatment with precise and optimal electric stimulation: opportunities
      and challenges.
AB  - PURPOSE OF REVIEW: Electric stimulation is a potent means of neuromodulation that
      has been used to restore hearing and minimize tremor, but its application on
      tinnitus symptoms has been limited. We examine recent evidence to identify the
      knowledge gaps in the use of electric stimulation for tinnitus treatment. RECENT
      FINDINGS: Recent studies using electric stimulation to suppress tinnitus in
      humans are categorized according to their points of attacks. First, noninvasive,
      direct current stimulation uses an active electrode in the ear canal, tympanic
      membrane, or temporal scalp. Second, inner ear stimulation uses charge-balanced
      biphasic stimulation by placing an active electrode on the promontory or round
      window, or a cochlear implant array in the cochlea. Third, intraneural implants
      can provide targeted stimulation of specific sites along the auditory pathway.
      Although these studies demonstrated some success in tinnitus suppression, none
      established a link between tinnitus suppression efficacy and tinnitus-generating
      mechanisms. SUMMARY: Electric stimulation provides a unique opportunity to
      suppress tinnitus. Challenges include matching electric stimulation sites and
      patterns to tinnitus locus and type, meeting the oftentimes-contradictory demands
      between tinnitus suppression and other indications, such as speech understanding,
      and justifying the costs and risks of electric stimulation for tinnitus symptoms.

PMID- 26208124
TI  - Red light-controlled polymerase chain reaction.
AB  - A 23-mer DNA "caged" at its 3'-terminus with a 9-anthracenyl moiety was prepared.
      It can be uncaged in the presence of photosensitizer (In(pyropheophorbide
      a)chloride)-containing DNAs (9-12 mers) and upon irradiation with red light. This
      mixture of DNAs was used to design red-light controlled polymerase chain
      reaction. 

PMID- 26208123
TI  - Controlled Assembly of Biocompatible Metallic Nanoaggregates Using a Small
      Molecule Crosslinker.
AB  - By introducing a capping step and controlling the reaction parameters, assembly
      of metallic nanoparticle aggregates can be achieved using a small-molecule
      crosslinker. Aggregates can be assembled from particles of varied size and
      composition and the size of the aggregates can be systematically adjusted.
      Following cell uptake of 60 nm aggregates, the aggregates are stable and nontoxic
      to macrophage cells up to 55 * 10(-3) m Au. 

PMID- 26208125
TI  - Histopathologic Findings of an Aberrant Internal Carotid Artery in the Temporal
      Bone With Fatal Complication.

PMID- 26208126
TI  - Refractory Positional Vertigo With Apogeotropic Horizontal Nystagmus After
      Labyrinthitis: Surgical Treatment and Identification of Dysmorphic Ampullae.
AB  - OBJECTIVES: To describe the rationale, intraoperative details, and
      histopathologic findings discovered when treating an unusual case of apogeotropic
      horizontal canal positional vertigo with a transmastoid labyrinthectomy. PATIENT:
      A single case report. INTERVENTION: Therapeutic. MAIN OUTCOME MEASURES:
      Resolution of apogeotropic nystagmus and improvement of positional vertigo.
      RESULTS: The apogeotropic variant of horizontal canal positional vertigo can be a
      difficult entity to treat. This report describes a patient who developed profound
      sensorineural hearing loss and vertigo after an acute left labyrinthitis. Ten
      months later, she developed vertigo with apogeotropic positional nystagmus
      involving the left horizontal semicircular canal. Particle repositioning
      maneuvers and vestibular physical therapy were unsuccessful. In addition, she
      developed intermittent positional vertigo affecting the ipsilateral vertical
      semicircular canals. Given the persistence of her vertigo, multiple canal
      involvement, and patient preference for definitive treatment, a transmastoid
      labyrinthectomy was performed. Intraoperatively, the ampulla of the horizontal
      canal as well as that of the other canals was grossly abnormal as later confirmed
      on histology. After surgery, her apogeotropic nystagmus and vertigo resolved, and
      her balance ability gradually improved to a highly functional level. CONCLUSION:
      This case illustrates a unique form of positional vertigo that developed and
      persisted after acute labyrinthitis. Conservative measures were unsuccessful and
      a transmastoid labyrinthectomy documented dense inflammatory tissue involving all
      three ampullae. We postulate that the post-labyrinthitic inflammatory changes
      resulted in mass loading of the membranous ampullae, causing abnormal nystagmus
      patterns and positional vertigo, which resolved after the labyrinthectomy.

PMID- 26208127
TI  - Cervical Spine Dysfunctions in Patients with Chronic Subjective Tinnitus.

PMID- 26208128
TI  - Prevention of Postoperative Cerebrospinal Fluid Leaks After Translabyrinthine
      Tumor Resection With Resorbable Mesh Cranioplasty.
AB  - OBJECTIVES: To evaluate the effectiveness of resorbable mesh cranioplasty at
      reducing postoperative cerebrospinal fluid (CSF) leak and pseudomeningocele
      formation after translabyrinthine tumor resection. STUDY DESIGN: Case series with
      chart review. SETTING: Tertiary academic referral center. PATIENTS: Fifty-three
      consecutive cases using a resorbable mesh cranioplasty after translabyrinthine
      tumor resection were reviewed. INTERVENTION: Temporal bone defects were repaired
      with a dural substitute, layered fat graft, and a resorbable mesh plate secured
      with screws. MAIN OUTCOME MEASURES: Primary outcome measures included the
      incidence of postoperative CSF wound leak or rhinorrhea, pseudomeningocele
      formation, and surgical site infection. RESULTS: Fifty-three cases (average age,
      54.0 yr; range, 19.3-75.1 yr) were analyzed. The average body mass index was 30.8
      kg/m2 (range, 17.9-48.3 kg/m2), and the average tumor size was 18.8 mm (range, 8
      38 mm). One patient (1.9%) experienced CSF rhinorrhea on postoperative Day 16,
      which resolved after transmastoid middle ear and eustachian tube packing. One
      patient (1.9%) experienced a surgical site infection requiring surgical
      debridement and mesh removal 4 months after surgery. Compared with 1,441 prior
      translabyrinthine surgeries analyzed from our institution using a traditional fat
      graft closure without mesh, the rate of postoperative CSF leak was significantly
      less using the resorbable mesh cranioplasty technique (p = 0.0483). CONCLUSION:
      Resorbable mesh cranioplasty is a safe and effective method to reduce
      postoperative CSF leak and pseudomeningocele formation after translabyrinthine
      craniotomy for tumor excision.

PMID- 26208129
TI  - Pulmonary Embolism and Infarct After Bilateral Cochlear Implantation in a Patient
      with Newly Diagnosed Sickle/beta+ Thalassemia.
AB  - OBJECTIVE: To heighten awareness of increased postoperative thromboembolic
      complications in patients with beta-hemoglobinopathies. PATIENT: A 42-year-old
      African American woman with previously undiagnosed beta-hemoglobinopathies
      suffers from sensorineural hearing loss caused by bacterial meningitis and
      undergoes bilateral cochlear implantation. INTERVENTION(S): Diagnostic:
      hemoglobin electrophoresis. Therapeutic: cochlear implantation, anticoagulation.
      MAIN OUTCOME MEASURE(S): Risk of thromboembolic event. RESULTS: Five days after
      surgery, the patient developed pulmonary embolism and infarct in the right lower
      lobe, which was treated with a 4-month course of anticoagulation. Hemoglobin
      electrophoresis showed that the patient had a previously undiagnosed rare beta
      hemoglobinopathy known as sickle/beta+ thalassemia. CONCLUSION: beta
      Hemoglobinopathies are associated with a higher incidence of thromboembolism;
      thus, they should be managed aggressively to prevent or treat perioperative
      thrombosis.

PMID- 26208130
TI  - Unresectable Recurrent Squamous Cell Carcinoma of the Temporal Bone Treated by
      Induction Chemotherapy Followed by Concurrent Chemo-Reirradiation: A Case Report
      and Review of the Literature.
AB  - OBJECTIVE: To report a rare case of recurrent temporal bone carcinoma encasing
      the carotid artery. PATIENT: A 54-year-old man underwent mastoidectomy combined
      with adjuvant chemoradiotherapy of squamous cell carcinoma of the temporal bone.
      He developed metastatic disease and received parotidectomy and lymph node
      dissection. Three months later, the magnetic resonance imaging scan showed that
      the tumor had relapsed and invaded the carotid artery. INTERVENTION: The patient
      completed TPF-C induction chemotherapy (docetaxel, cisplatin, 5-fluorouracil,
      cetuximab), followed by concurrent chemotherapy with reirradiation. RESULTS:
      Magnetic resonance imaging revealed a complete response of tumor 1 month after
      treatment. The patient had no detectable recurrence after 53 months of follow-up.
      CONCLUSION: Concurrent chemotherapy with reirradiation is a potential curative
      treatment option for patients who have unresectable recurrent squamous cell
      carcinoma of the temporal bone.

PMID- 26208131
TI  - Hydrodistension with or without fulguration of hunner lesions for interstitial
      cystitis: Long-term outcomes and prognostic predictors.
AB  - AIMS: Hydrodistension of the bladder, with optional fulguration of Hunner
      lesions, is one of the recommended therapies for interstitial cystitis (IC). The
      aims of this study are to evaluate long-term outcomes of hydrodistension and
      identify outcome predictors. METHODS: The study cohort was 191 newly diagnosed IC
      patients (155 women and 36 men) who underwent hydrodistension with fulguration of
      Hunner lesions if detected between 2007 and 2013 at our institution. The primary
      outcome was therapeutic failure, which was defined as repeat hydrodistension,
      bladder instillation therapy, or narcotic use for pain control. Clinical
      features, including comorbidities and endoscopic findings, were analyzed along
      with the outcome. RESULTS: The cohort comprised 126 patients of Hunner type IC
      and 65 patients of non-Hunner type IC. The mean time to therapeutic failure was
      28.5 months in Hunner type IC and 25.2 months in non-Hunner type IC. The
      therapeutic failure rate was higher in non-Hunner type IC at 17.3 months;
      however, the long-term outcomes reversed thereafter. The mean time to therapeutic
      failure was shorter in patients with lumbar spinal stenosis (LSS) or irritable
      bowel syndrome (IBS). Multivariate analysis identified LSS as a predictor for
      failure in Hunner type IC and non-Hunner type IC (HR = 18.8, P = 0.001; HR = 3.8,
      P = 0.028, respectively) and IBS in non-Hunner type IC (HR = 18.0, P = 0.008).
      CONCLUSIONS: Bladder hydrodistension, with fulguration of the Hunner lesions,
      improved IC symptoms. The outcome was worse in non-Hunner type IC shortly after
      hydrodistension but eventually comparable across the two types. Concomitant LSS
      and IBS were predictors for poor outcome. Neurourol. Urodynam. 35:965-969, 2016.
      (c) 2015 Wiley Periodicals, Inc.

PMID- 26208132
TI  - Isolation and structural elucidation of a novel homogenous polysaccharide from
      Tricholoma matsutake.
AB  - A crude polysaccharide possessing antitumour, radiation-resistant and anti-ageing
      attributes was extracted from Tricholoma matsutake by water extraction and
      alcohol precipitation. From this crude polysaccharide, a homogeneous
      polysaccharide, TMP-5II, was successfully purified by Sephacryl S-300 column
      chromatography. The average molecular weight (Mw) of TMP-5II was 15.76 kDa.
      Monosaccharide analysis indicated that the homogeneous polysaccharide contained
      four different residues: d-glucose, d-galactose, d-mannose and d-fucose.
      Attenuated total reflectance infrared spectroscopy revealed characteristics
      typical of carbohydrate polymers and a peak typical of a beta-type glycosidic
      bond. TMP-5II was selected for structural characterisation by nuclear magnetic
      resonance (NMR) analysis. According to (1)H NMR, (13)C NMR and two-dimensional
      NMR analysis, TMP-5II contains two kinds of linkages, beta and alpha, at a ratio
      of 4:1. Preliminary results indicated that the polysaccharide had (1-4)-beta
      pyran glucose as the main chain, and a branched chain in the O-6 location with
      fucose (1-2) mannose (1-3)-alpha-pyran galactose. 

PMID- 26208133
TI  - Targeted delivery of doxorubicin and vincristine to lymph cancer: evaluation of
      novel nanostructured lipid carriers in vitro and in vivo.
AB  - PURPOSE: Lymph cancers are heterogeneous malignancies of the hematopoietic and
      lymphoid tissues. Doxorubicin (DOX) and vincristine (VCR) are commonly used anti
      cancer chemotherapeutic drugs, but their clinical uses are associated with dose
      limiting systemic toxicity. METHODS: In the present study, DOX and VCR were
      encapsulated into nanostructured lipid carriers (NLCs) and used them to treat B
      cell lymphoma cells through the targeted delivery of DOX and VCR to lymph cancer
      animal model. RESULTS: DOX and VCR encapsulated NLCs (DOX/VCR NLCs) demonstrated
      controlled drug release under physiological conditions. In addition, DOX/VCR NLCs
      exhibited the highest cytotoxicity and synergistic effect of two drugs in B-cell
      lymphoma cells and the best anti-tumor effect in vivo. CONCLUSION: DOX/VCR NLCs
      were proved to be more efficacious than the equivalent dose of free DOX and
      single drug (DOX or VCR) formulation in vitro and in vivo, and significantly
      reduced the drug-associated systemic toxicity.

PMID- 26208134
TI  - Within-Gender Changes in HIV Prevalence among Adults between 2005/6 and 2010/11
      in Zimbabwe.
AB  - INTRODUCTION: Zimbabwe has reported significant declines in HIV prevalence
      between 2005/06 and 2010/11 Demography and Health Surveys; a within-gender
      analysis to identify the magnitude and factors associated with this change, which
      can be masked, is critical for targeting interventions. METHODS: We analyzed
      change in HIV prevalence for 6,947 women and 5,848 men in the 2005/06 survey and
      7,313 women and 6,250 men in 2010/11 surveys using 2005/06 as referent. The data
      was analyzed taking into consideration the survey design and therefore the svy,
      mean command in Stata was used in both linear and logistic regression. RESULTS:
      There were similar proportional declines in prevalence at national level for
      males (15% p=0.011) and females (16%,p=0.008). However, there were variations in
      decline by provincial setting, demographic variables of age, educational level
      and some sexual risk behaviours. In logistic regression analysis, statistically
      significant declines were observed among men in Manicaland, Mashonaland East and
      Harare (p<0.01) and for women in Manicaland, Mashonaland Central and Harare
      (p<0.01). Although not statistically significant, numerical increases were
      observed among men in Matebeleland North, Matebeleland South, Midlands and for
      both men and women in Bulawayo. Young women in the age range 15-34 experienced a
      decline in prevalence (p<0.01) while older men 30-44 had a statistically
      significant decline (p<0.01). Having a secondary and above education, regardless
      of employment status for both men and women recorded a significant decline. For
      sexual risk behaviours, currently in union for men and women and not in union for
      women there was a significant decline in prevalence. CONCLUSION: Zimbabwe has
      reported a significant decline among both men and women but there are important
      differentials across provinces, demographic characteristics and sexual risk
      behaviours that suggest that the epidemic in Zimbabwe is heterogeneous and
      therefore interventions must be targeted in order to achieve epidemic control.

PMID- 26208135
TI  - Technical and Energy Performance of an Advanced, Aqueous Ammonia-Based CO2
      Capture Technology for a 500 MW Coal-Fired Power Station.
AB  - Using a rate-based model, we assessed the technical feasibility and energy
      performance of an advanced aqueous-ammonia-based postcombustion capture process
      integrated with a coal-fired power station. The capture process consists of three
      identical process trains in parallel, each containing a CO2 capture unit, an NH3
      recycling unit, a water separation unit, and a CO2 compressor. A sensitivity
      study of important parameters, such as NH3 concentration, lean CO2 loading, and
      stripper pressure, was performed to minimize the energy consumption involved in
      the CO2 capture process. Process modifications of the rich-split process and the
      interheating process were investigated to further reduce the solvent regeneration
      energy. The integrated capture system was then evaluated in terms of the mass
      balance and the energy consumption of each unit. The results show that our
      advanced ammonia process is technically feasible and energy-competitive, with a
      low net power-plant efficiency penalty of 7.7%.

PMID- 26208136
TI  - Precore/Core Region Mutations in Hepatitis B Virus DNA Predict Postoperative
      Survival in Hepatocellular Carcinoma.
AB  - Hepatitis B virus (HBV) DNA is prone to mutations because of the proofreading
      deficiencies of HBV polymerase. We have identified hepatocellular carcinoma (HCC)
      survival-associated HBV mutations in the X protein region of HBV DNA. In the
      present study, we extend our research to assess HCC survival-associated HBV
      mutations in the HBV precore/core (PreC/C) region. The PreC/C region was
      amplified and sequenced and the HBV mutations were identified according to the
      NCBI database (http://www.ncbi.nlm.nih.gov/genome/5536). The relationships
      between the mutations in the PreC/C region and HCC survival were analyzed.
      Survival curves were generated using the Kaplan-Meier method, and comparisons
      between the curves were made using the log-rank test. Multivariate survival
      analysis was performed using a Cox proportional hazards model. After adjusting
      for clinical characteristics, the 1915, 2134, 2221, 2245 and 2288 mutational
      sites were identified as statistically significant independent predictors of HCC
      survival by multivariate survival analysis using a Cox proportional hazards
      model. In addition, the mutational site of 1896 was identified for its
      association with survival at a borderline significance level. A total of five
      mutations in the precore/core region were identified as independent predictors of
      postoperative survival in HCC patients. The analysis of HBV DNA mutations may
      help identify patient subgroups with poor prognosis and may help refine
      therapeutic decisions regarding HCC patients. 

PMID- 26208137
TI  - Cationic Pd(II)-Catalyzed Cyclization of N-Tosyl-aniline Tethered Allenyl
      Aldehydes with Arylboronic Acids: Diastereo- and Enantioselective Synthesis of
      Tetrahydroquinoline Derivatives.
AB  - An efficient cyclization of N-tosyl-aniline tethered allenyl aldehydes and
      arylboronic acids catalyzed by cationic palladium complex is developed. This
      annulation reaction provides a convenient process for the synthesis of 3,4-cis
      1,2,3,4-tetrahydroquinoline derivatives in high yields with excellent
      diastereoselectivity and enantioselectivity. 

PMID- 26208138
TI  - Feeding Solanum glaucophyllum to preparturient multiparous cows prevents
      postparturient hypocalcemia.
AB  - Solanum glaucophyllum (SG) contains 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)
      glycosides. We investigated the effect of SG on hypocalcemia in cows. Serum
      levels of 1,25-(OH)2D3, total calcium and phosphorus dose-relatedly increased
      after feeding with SG, while serum magnesium and chloride levels fell (P < 0.05).
      We also performed an ethylenediaminetetraacetic acid (EDTA) infusion to induce
      artificial hypocalcemia. Cows that had been fed 4.0 mg/kg body weight of SG daily
      for 2 weeks had a higher serum concentration of total calcium at the end of EDTA
      infusion than those not fed SG (P < 0.05). In a field trial, multiparous cows
      were assigned to one of four groups: (1) no SG, (2) 1.3 g or (3) 2.6 g of SG
      daily from 14 days before the estimated calving day until 3 days after calving,
      or (4) a single feed of 35.75 g SG at 3 days before the estimated calving day.
      The concentrations of serum total calcium after the calving in each treatment
      group were (1) 7.4, (2) 7.9, (3) 8.0 and (4) 8.9 mg/dL and higher for (4) than
      for (1) (P < 0.05). The data suggests that feeding a high dose of SG before the
      calving may maintain higher concentrations of serum calcium after the calving.

PMID- 26208140
TI  - Pb3[C6(CH3)3(CO2)3H6]2[DMF]3: first layered Pb-Kemp's triacid complex.
AB  - An unprecedented layered Pb-Kemp's triacid compound,
      Pb3[C6(CH3)3(CO2)3H6]2[DMF]3, has been synthesized. The material exhibits a
      selective CO2 adsorption, a reversible DMF coordination, and an intercalative
      hexanal addition reaction. A competing crystallization reaction under
      solvothermal conditions using Pb(2+) and Cd(2+) with Kemp's triacid reveals
      higher selectivity of Cd(2+) over Pb(2+). 

PMID- 26208139
TI  - Co-occurring Synechococcus ecotypes occupy four major oceanic regimes defined by
      temperature, macronutrients and iron.
AB  - Marine picocyanobacteria, comprised of the genera Synechococcus and
      Prochlorococcus, are the most abundant and widespread primary producers in the
      ocean. More than 20 genetically distinct clades of marine Synechococcus have been
      identified, but their physiology and biogeography are not as thoroughly
      characterized as those of Prochlorococcus. Using clade-specific qPCR primers, we
      measured the abundance of 10 Synechococcus clades at 92 locations in surface
      waters of the Atlantic and Pacific Oceans. We found that Synechococcus partition
      the ocean into four distinct regimes distinguished by temperature, macronutrients
      and iron availability. Clades I and IV were prevalent in colder, mesotrophic
      waters; clades II, III and X dominated in the warm, oligotrophic open ocean;
      clades CRD1 and CRD2 were restricted to sites with low iron availability; and
      clades XV and XVI were only found in transitional waters at the edges of the
      other biomes. Overall, clade II was the most ubiquitous clade investigated and
      was the dominant clade in the largest biome, the oligotrophic open ocean. Co
      occurring clades that occupy the same regime belong to distinct evolutionary
      lineages within Synechococcus, indicating that multiple ecotypes have evolved
      independently to occupy similar niches and represent examples of parallel
      evolution. We speculate that parallel evolution of ecotypes may be a common
      feature of diverse marine microbial communities that contributes to functional
      redundancy and the potential for resiliency. 

PMID- 26208141
TI  - TLR2 and TLR4 Expression and Inflammatory Cytokines are Altered in the Airway
      Epithelium of Those with Alcohol Use Disorders.
AB  - BACKGROUND: The lung has a highly regulated system of innate immunity to protect
      itself from inhaled microbes and toxins. The first line of defense is mucociliary
      clearance, but if invaders overcome this, inflammatory pathways are activated.
      Toll-like receptors (TLRs) are expressed on the airway epithelium. Their
      signaling initiates the inflammatory cascade and leads to production of
      inflammatory cytokines such as interleukin (IL)-6 and IL-8. We hypothesized that
      airway epithelial insults, including heavy alcohol intake or smoking, would alter
      the expression of TLRs on the airway epithelium. METHODS: Bronchoscopy with
      bronchoalveolar lavage and brushings of the airway epithelium was performed in
      otherwise healthy subjects who had normal chest radiographs and spirometry. A
      history of alcohol use disorders (AUDs) was ascertained using the Alcohol Use
      Disorders Identification Test (AUDIT), and a history of cigarette smoking was
      also obtained. Age, gender, and nutritional status in all groups were similar. We
      used real-time polymerase chain reaction (PCR) to quantitate TLR1 to 9 and enzyme
      linked immune assay to measure tumor necrosis factor-alpha, IL-6, and IL-8.
      RESULTS: Airway brushings were obtained from 26 nonsmoking/non-AUD subjects, 28
      smoking/non-AUD subjects, 36 smoking/AUD subjects, and 17 nonsmoking/AUD
      subjects. We found that TLR2 is up-regulated in AUD subjects, compared to
      nonsmoking/non-AUD subjects, and correlated with their AUDIT scores. We also
      measured a decrease in TLR4 expression in AUD subjects that correlated with AUDIT
      score. IL-6 and IL-8 were also increased in bronchial washings from AUD subjects.
      CONCLUSIONS: We have previously demonstrated in normal human bronchial epithelial
      cells that in vitro alcohol exposure up-regulates TLR2 through a NO/cGMP/PKG
      dependent pathway, resulting in up-regulation of inflammatory cytokine production
      after Gram-positive bacterial product stimulation. Our current translational
      study confirms that TLR2 is also up-regulated in humans with AUDs.

PMID- 26208143
TI  - Condensation Enhancement by Surface Porosity: Three-Stage Mechanism.
AB  - Surface defects, such as pores, cracks, and scratches, are naturally occurring
      and commonly found on solid surfaces. However, the mechanism by which such
      imperfections promote condensation has not been fully explored. In the current
      paper we thermodynamically analyze the ability of surface porosity to enhance
      condensation on a hydrophilic solid. We show that the presence of a surface
      embedded pore brings about three distinct stages of condensation. The first is
      capillary condensation inside the pore until it is full. This provides an ideal
      hydrophilic surface for continuing the condensation. As a result, spontaneous
      condensation and wetting can be achieved at lower vapor pressure than on a smooth
      surface. 

PMID- 26208142
TI  - A Novel Interaction between FLICE-Associated Huge Protein (FLASH) and E2A
      Regulates Cell Proliferation and Cellular Senescence via Tumor Necrosis Factor
      (TNF)-Alpha-p21WAF1/CIP1 Axis.
AB  - Dysregulation of the cell proliferation has been implicated in the
      pathophysiology of a number of diseases. Cellular senescence limits proliferation
      of cancer cells, preventing tumorigenesis and restricting tissue damage. However,
      the role of cellular senescence in proliferative nephritis has not been
      determined. The proliferative peak in experimental rat nephritis coincided with a
      peak in E2A expression in the glomeruli. Meanwhile, E12 (an E2A-encoded
      transcription factor) did not promote proliferation of Mesangial cells (MCs) by
      itself. We identified caspase-8-binding protein FLICE-associated huge protein
      (FLASH) as a novel E2A-binding partner by using a yeast two-hybrid screening.
      Knockdown of FLASH suppressed proliferation of MCs. This inhibitory effect was
      partially reversed by the knockdown of E2A. In addition, the knockdown of FLASH
      induced cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) expression, but did
      not affect p53 expression. Furthermore, overexpression of E12 and E47 induced
      p21, but not p53 in MCs, in the absence of FLASH. We also demonstrated that E2A
      and p21 expression at the peak of proliferation was followed by significant
      induction of FLASH in mesangial areas in rat proliferative glomerulonephritis.
      Moreover, we revealed that FLASH negatively regulates cellular senescence via the
      interaction with E12. We also demonstrated that FLASH is involved in the TNF
      alpha-induced p21 expressions. These results suggest that the functional
      interaction of E2A and FLASH play an important role in cell proliferation and
      cellular senescence via regulation of p21 expression in experimental
      glomerulonephritis. 

PMID- 26208144
TI  - Low-cost flexible supercapacitors with high-energy density based on
      nanostructured MnO2 and Fe2O3 thin films directly fabricated onto stainless
      steel.
AB  - The facile and economical electrochemical and successive ionic layer adsorption
      and reaction (SILAR) methods have been employed in order to prepare manganese
      oxide (MnO2) and iron oxide (Fe2O3) thin films, respectively with the fine
      optimized nanostructures on highly flexible stainless steel sheet. The symmetric
      and asymmetric flexible-solid-state supercapacitors (FSS-SCs) of nanostructured
      (nanosheets for MnO2 and nanoparticles for Fe2O3) electrodes with
      Na2SO4/Carboxymethyl cellulose (CMC) gel as a separator and electrolyte were
      assembled. MnO2 as positive and negative electrodes were used to fabricate
      symmetric SC, while the asymmetric SC was assembled by employing MnO2 as positive
      and Fe2O3 as negative electrode. Furthermore, the electrochemical features of
      symmetric and asymmetric SCs are systematically investigated. The results verify
      that the fabricated symmetric and asymmetric FSS-SCs present excellent
      reversibility (within the voltage window of 0-1 V and 0-2 V, respectively) and
      good cycling stability (83 and 91%, respectively for 3000 of CV cycles).
      Additionally, the asymmetric SC shows maximum specific capacitance of 92 Fg(-1),
      about 2-fold of higher energy density (41.8 Wh kg(-1)) than symmetric SC and
      excellent mechanical flexibility. Furthermore, the "real-life" demonstration of
      fabricated SCs to the panel of SUK confirms that asymmetric SC has 2-fold higher
      energy density compare to symmetric SC.

PMID- 26208145
TI  - Effect of Antibiotics and Antibiofilm Agents in the Ultrastructure and
      Development of Biofilms Developed by Nonpigmented Rapidly Growing Mycobacteria.
AB  - We analyze the effect of amikacin, ciprofloxacin, and clarithromycin, alone and
      associated with N-acetylcysteine (NAC) and Tween 80, at different times and
      concentrations in nonpigmented rapidly growing mycobacteria (NPRGM) biofilms. For
      this purpose, confocal laser scanning microscopy and image analysis were used to
      study the development and behavior of intrinsic autofluorescence, covered area,
      thickness, and cell viability in NPRGM biofilms after adding antibiotics alone
      and associated with antibiofilm agents. In this study, ciprofloxacin is the most
      active antibiotic against this type of biofilm and thickness is the most affected
      parameter. NAC and Tween 80 combined with antibiotics exert a synergistic effect
      in increasing the percentage of dead bacteria and also reducing the percentage of
      covered surface and thickness of NPRGM biofilms. Tween 80 seems to be an
      antibiofilm agent more effective than NAC due to its higher reduction in the
      percentage of cover surface and thickness. In conclusion, the results obtained in
      this work show that phenotypic parameters (thickness, percentage of covered
      surface, autofluorescence, percentage of live/dead bacteria) are affected by
      combining antibiotics and antibiofilm agents, ciprofloxacin and Tween 80 being
      the most active agents against NPRGM biofilms. 

PMID- 26208146
TI  - Dynamic facial expressions are processed holistically, but not more holistically
      than static facial expressions.
AB  - There is evidence that facial expressions are perceived holistically and
      featurally. The composite task is a direct measure of holistic processing
      (although the absence of a composite effect implies the use of other types of
      processing). Most composite task studies have used static images, despite the
      fact that movement is an important aspect of facial expressions and there is some
      evidence that movement may facilitate recognition. We created static and dynamic
      composites, in which emotions were reliably identified from each half of the
      face. The magnitude of the composite effect was similar for static and dynamic
      expressions identified from the top half (anger, sadness and surprise) but was
      reduced in dynamic as compared to static expressions identified from the bottom
      half (fear, disgust and joy). Thus, any advantage in recognising dynamic over
      static expressions is not likely to stem from enhanced holistic processing,
      rather motion may emphasise or disambiguate diagnostic featural information. 

PMID- 26208147
TI  - The credibility of exposure therapy: Does the theoretical rationale matter?
AB  - OBJECTIVE: Little is understood about how the public perceives exposure-based
      therapy (ET) for treating anxiety and trauma-related disorders or how ET
      rationales affect treatment credibility. Distinct approaches to framing ET are
      practiced, including those emphasized in traditional cognitive behavioral
      therapy, acceptance and commitment therapy, and the more recent inhibitory
      learning model. However, their relative effect on ET's credibility remains
      unknown. METHOD: A final sample of 964 U.S. adults provided baseline views of ET.
      Participants rated ET treatment credibility following a simple ET definition (pre
      rationale) and following randomization to rationale modules addressing ET goals,
      fear, and cognitive strategies from distinct theoretical perspectives (post
      rationale). Baseline ET views, symptoms, and sociodemographic characteristics
      were examined as putative moderators and predictors. RESULTS: At baseline, the
      majority had never heard of ET. From pre- to post-rationale, ET treatment
      credibility significantly increased but the rationales' theoretical perspective
      had little impact. More negative baseline ET views, specific ethnic/racial
      minority group status, and lower education moderated or predicted greater
      increases in treatment credibility following the rationale. CONCLUSIONS: ET
      remains relatively unknown as a treatment for anxiety or trauma, supporting the
      need for direct-to-consumer marketing. Diverse theory-driven rationales similarly
      increased ET credibility, particularly among those less likely to use ET.

PMID- 26208148
TI  - iTRAQ-Based Quantitative Proteomic Analysis of the Antimicrobial Mechanism of
      Peptide F1 against Escherichia coli.
AB  - Antimicrobial peptides have received increasing attention in the agricultural and
      food industries due to their potential to control pathogens. However, to
      facilitate the development of novel peptide-based antimicrobial agents, details
      regarding the molecular mechanisms of these peptides need to be elucidated. The
      aim of this study was to investigate the antimicrobial mechanism of peptide F1, a
      bacteriocin found in Tibetan kefir, against Escherichia coli at protein levels
      using iTRAQ-based quantitative proteomic analysis. In response to treatment with
      peptide F1, 31 of the 280 identified proteins in E. coli showed alterations in
      their expression, including 10 down-regulated proteins and 21 up-regulated
      proteins. These 31 proteins all possess different molecular functions and are
      involved in different molecular pathways, as is evident in referencing the Kyoto
      Encyclopedia of Genes and Genomes pathways. Specifically, pathways that were
      significantly altered in E. coli in response to peptide F1 treatment include the
      tricarboxylic acid cycle, oxidative phosphorylation, glycerophospholipid
      metabolism, and the cell cycle-caulobacter pathways, which was also associated
      with inhibition of the cell growth, induction of morphological changes, and cell
      death. The results provide novel insights into the molecular mechanisms of
      antimicrobial peptides. 

PMID- 26208149
TI  - An entomological and seroepidemiological study of the vectorial-transmission risk
      of Chagas disease in the coast of northern Chile.
AB  - Four species of triatomines are known from Chile: Triatoma infestans Klug,
      Mepraia spinolai Porter, M. gajardoi Frias, Henry & Gonzalez, and M. parapatrica
      Frias (Hemiptera: Reduviidae), the last three are endemic. The geographical
      distribution of M. gajardoi includes the coastal areas in the north of Chile
      between 18 degrees  and 21 degrees S, an area with both a resident workforce and
      summer-season visitors. A study was developed to assess the risk of vectorial
      transmission of Chagas disease by M. gajardoi in hut settlements on the coast of
      the Tarapaca Region, in particular in Caleta San Marcos and Caleta Rio Seco. The
      study comprised fingerstick sampling of 95 persons, venous samples from 29
      domestic dogs and capture of 52 triatomines, from both fishing coves. The samples
      were analysed by enzyme-linked immunosorbent assay (ELISA) and polymerase chain
      reaction (PCR) techniques. The results show that, of the total number of persons
      studied, 100% were negative for Trypanosoma cruzi Chagas (Trypanosomatida:
      Trypanosomatidae) antibodies, 10.34% of canids were positive for the antibody and
      5.8% of M. gajardoi were infected to the PCR technique. The presence of this
      species in areas close to human settlements constitutes a risk to human
      populations established on the coast of northern Chile. 

PMID- 26208150
TI  - Short versus Long Gonadotropin-Releasing Hormone Analogue Suppression Protocols
      in IVF/ICSI Cycles in Patients of Various Age Ranges.
AB  - OBJECTIVE: To compare the two GnRH-a protocols (long GnRH-a protocol and short
      GnRH-a protocol) for ovarian stimulation in IVF/ICSI cycles in patients of
      various age ranges. METHODS: A total of 5662 IVF-ET/ICSI cycles from 2010 to 2013
      were retrospectively identified. The cycles were divided into two groups: a long
      protocol group and short protocol group. In each group, the patients were divided
      into four age ranges: <31 years, 31 to 35 years, 36 to 40 years, and >40 years.
      The duration of stimulation, total dose of Gn, implantation rate and pregnancy
      rate were compared. RESULTS: The total dose of Gn was significantly higher, and
      the duration of stimulation was significantly longer, in the long protocol group
      than in the short protocol group for all age ranges (P<0.05). If the patients
      were of the same age range, the number of oocytes retrieved, MII oocytes, and
      high-quality embryos in the long protocol group were all significantly greater
      than those in the short protocol group (P<0.05). In the long protocol group, the
      clinical pregnancy rates of the four age ranges were 52.76%, 44.33%, 36.15% and
      13.33%, respectively, which were significantly higher than those in the short
      protocol group (33.33%, 24.58%, 22.49% and 8.72%, respectively; P<0.05). The same
      trend was also found in the implantation rates of the four age ranges. As the age
      increased, the clinical pregnancy and implantation rates, as well as the number
      of oocytes retrieved, MII oocytes, and high-quality embryos, of the long protocol
      group significantly decreased (P<0.05). CONCLUSIONS: Our study demonstrated that
      regardless of patient age, the long protocol was superior to the short protocol
      in terms of the number of retrieved oocytes, as well as the implantation and
      pregnancy rates.

PMID- 26208151
TI  - Vpx-Independent Lentiviral Transduction and shRNA-Mediated Protein Knock-Down in
      Monocyte-Derived Dendritic Cells.
AB  - The function of dendritic cells (DCs) in the immune system is based on their
      ability to sense and present foreign antigens. Powerful tools to research DC
      function and to apply in cell-based immunotherapy are either silencing or
      overexpression of genes achieved by lentiviral transduction. To date, efficient
      lentiviral transduction of DCs or their monocyte derived counterparts (MDDCs)
      required high multiplicity of infection (MOI) or the exposure to the HIV-2/SIV
      protein Vpx to degrade viral restriction factor SAM domain and HD domain
      containing protein 1 (SAMHD1). Here we present a Vpx-independent method for
      efficient (>95%) transduction of MDDCs at lower MOI. The protocol can be used
      both for ectopic gene expression and knock-down. Introducing shRNA targeting
      viral entry receptor CD4 and restriction factor SAMHD1 into MDDCs resulted in
      down-regulation of targeted proteins and, consequently, expected impact on HIV
      infection. This protocol for MDDCs transduction is robust and free of the
      potential risk arising from the use of Vpx which creates a virus infection-prone
      environment, potentially dangerous in clinical setting. 

PMID- 26208152
TI  - Correction: Alcohol-Preferring Rats Show Goal Oriented Behaviour to Food
      Incentives but Are Neither Sign-Trackers Nor Impulsive.

PMID- 26208153
TI  - A virtual geometric morphometric approach to the quantification of long bone
      bilateral asymmetry and cross-sectional shape.
AB  - OBJECTIVE: The widespread use of three-dimensional digitization means that models
      of whole bone geometry are routinely captured for many applications in virtual
      anthropology. In this article, we test whether a geometric morphometric (GMM)
      approach can be used to accurately quantify directional bilateral asymmetry in
      cross-sectional shape using virtual bone models. METHODS: We introduce a method
      to (1) orient virtual long bone models and extract cross sections and (2) collect
      GMM landmarks to analyze cross-sectional shape. Landmark data, captured using
      polar radii, were analyzed for an example study set of paired humeri from Andaman
      Islanders sampled at 35%, 50%, and 65% locations. RESULTS: The GMM method can (1)
      detect significant differences in left and right cross-sectional shape and (2)
      allow the directionality of shape change (distribution of bone from centroid) to
      be evaluated in the context of whole outline shape and in relation to the axis of
      maximum bending rigidity. The protocol may be used with models created from laser
      (surface) scan or computed tomography (CT) scan data, and applied to cross
      sectional images that were collected using periosteal molding techniques.
      CONCLUSIONS: The results demonstrate directional bilateral asymmetry in shape,
      but do not recover the same signal for size measurements. Our method offers a
      pathway to quantify both the pattern of variation in shape and the relationship
      between size and shape variation, opening new questions about how those patterns
      manifest over ontogeny, change temporally or differ in relation to the nature and
      intensity of the activity, and bone loading conditions.

PMID- 26208156
TI  - ?

PMID- 26208157
TI  - ?

PMID- 26208158
TI  - ?

PMID- 26208159
TI  - ?

PMID- 26208161
TI  - ?

PMID- 26208160
TI  - ?

PMID- 26208162
TI  - ?

PMID- 26208163
TI  - Cutaneous cryosurgery in the United States.
AB  - BACKGROUND: Cryosurgery is a common treatment modality for many dermatological
      conditions; however, the extent to which it is used and by which medical
      specialties is not well characterized. OBJECTIVE: To determine the rates of
      cryosurgery use over time, the top dermatoses treated by cryosurgery, patient
      demographics and the rate at which practitioners used cryosurgery. METHODS: We
      used the National Ambulatory Medical Care Survey (NAMCS) from 1993 to 2010 in
      order to quantify the use of cryosurgery in outpatient offices. For visits where
      cryosurgery was utilized, the leading diagnoses, treating physician specialties,
      and patient ages were tabulated. RESULTS: Cryosurgery was most commonly used for
      treating actinic keratoses (48% of visits), seborrheic keratoses (25% of visits)
      and verrucae (21% of visits). Dermatologists performed 82% of all cryosurgeries,
      followed by family/internal medicine physicians (13.6%) and pediatricians (2.8%).
      The use of cryosurgery for these dermatoses has increased over time (p < 0.0001),
      especially in patients over the age of 65 years. Physicians in offices with
      health maintenance organization-based practices were more likely to utilize
      cryosurgery. LIMITATIONS: Since NAMCS data are cross-sectional, we are unable to
      determine whether patients tried and failed other treatments. CONCLUSIONS: As the
      baby boomer generation ages, the demand for cryosurgery will likely further
      increase.

PMID- 26208164
TI  - Dissociation of Axonal Neurofilament Content from Its Transport Rate.
AB  - The axonal cytoskeleton of neurofilament (NF) is a long-lived network of fibrous
      elements believed to be a stationary structure maintained by a small pool of
      transported cytoskeletal precursors. Accordingly, it may be predicted that NF
      content in axons can vary independently from the transport rate of NF. In the
      present report, we confirm this prediction by showing that human NFH transgenic
      mice and transgenic mice expressing human NFL Ser55 (Asp) develop nearly
      identical abnormal patterns of NF accumulation and distribution in association
      with opposite changes in NF slow transport rates. We also show that the rate of
      NF transport in wild-type mice remains constant along a length of the optic axon
      where NF content varies 3-fold. Moreover, knockout mice lacking NFH develop even
      more extreme (6-fold) proximal to distal variation in NF number, which is
      associated with a normal wild-type rate of NF transport. The independence of
      regional NF content and NF transport is consistent with previous evidence
      suggesting that the rate of incorporation of transported NF precursors into a
      metabolically stable stationary cytoskeletal network is the major determinant of
      axonal NF content, enabling the generation of the striking local variations in NF
      number seen along axons. 

PMID- 26208165
TI  - In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of
      Intrauterine Growth Restriction (IUGR).
AB  - BACKGROUND: Intrauterine growth restriction (IUGR) is a risk factor for abnormal
      neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging
      (MRI) and spectroscopy (MRS), to assess in vivo brain structural and metabolic
      consequences, and identify potential metabolic biomarkers for clinical
      translation. METHODS: IUGR was induced in 3 pregnant rabbits at gestational day
      25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn
      was used as control. Fetuses were delivered at day 30 and weighted. A total of 6
      controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the
      first 8 hours of life, at 7T. Changes in brain tissue volumes and respective
      contributions to each MRS voxel were estimated by semi-automated registration of
      MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i)
      absolute metabolite quantifications, using linear fitting; (ii) local temperature
      estimations, based on the water chemical shift; and (iii) classification, using
      spectral pattern analysis. RESULTS: Lower birth weight was associated with (i)
      smaller brain sizes, (ii) slightly lower brain temperatures, and (iii)
      differential metabolite profile changes in specific regions of the brain
      parenchyma. Specifically, we found estimated lower levels of aspartate and N
      acetylaspartate (NAA) in the cerebral cortex and hippocampus (suggesting neuronal
      impairment), and higher glycine levels in the striatum (possible marker of brain
      injury). Our results also suggest that the metabolic changes in cortical regions
      are more prevalent than those detected in hippocampus and striatum. CONCLUSIONS:
      IUGR was associated with brain metabolic changes in vivo, which correlate well
      with the neurostructural changes and neurodevelopment problems described in IUGR.
      Metabolic parameters could constitute non invasive biomarkers for the diagnosis
      and abnormal neurodevelopment of perinatal origin.

PMID- 26208166
TI  - Surveillance and Care of the Gynecologic Cancer Survivor.
AB  - BACKGROUND: Care of the gynecologic cancer survivor extends beyond cancer
      treatment to encompass promotion of sexual, cardiovascular, bone, and brain
      health; management of fertility, contraception, and vasomotor symptoms; and
      genetic counseling. METHODS: This is a narrative review of the data and
      guidelines regarding care and surveillance of the gynecologic cancer survivor. We
      searched databases including PubMed, Cochrane, and Scopus using the search terms
      gynecologic cancer, cancer surveillance, and cancer survivor and reached a
      consensus for articles chosen for inclusion in the review based on availability
      in the English language and publication since 2001, as well as key older
      articles, consensus statements, and practice guidelines from professional
      societies. However, we did not undertake an extensive systematic search of the
      literature to identify all potentially relevant studies, nor did we utilize
      statistical methods to summarize data. We offer clinical recommendations for the
      management of gynecologic cancer survivors based on review of evidence and our
      collective clinical experience. RESULTS: Key messages include the limitations of
      laboratory studies, including CA-125, and imaging in the setting of gynecologic
      cancer surveillance, hormonal and non-hormonal management of treatment-related
      vasomotor symptoms and genitourinary syndrome of menopause, as well as
      recommendations for general health screening, fertility preservation, and
      contraception. CONCLUSIONS: A holistic approach to care extending beyond cancer
      treatment alone benefits gynecologic cancer survivors. In addition to
      surveillance for cancer recurrence and late treatment side effects, survivors
      benefit from guidance on hormonal, contraceptive, and fertility management and
      promotion of cardiovascular, bone, brain, and sexual health.

PMID- 26208167
TI  - Coaxial Electrospray of Curcumin-Loaded Microparticles for Sustained Drug
      Release.
AB  - Curcumin exhibits superior anti-inflammatory, antiseptic and analgesic activities
      without significant side effects. However, clinical dissemination of this natural
      medicine is limited by its low solubility and poor bio-availability. To overcome
      this limitation, we propose to encapsulate curcumin in poly(lactic-co-glycolic
      acid) (PLGA) microparticles (MPs) by an improved coaxial electrospray (CES)
      process. This process is able to generate a stable cone-jet mode in a wide range
      of operation parameters in order to produce curcumin-loaded PLGA MPs with a clear
      core-shell structure and a designated size of several micrometers. In order to
      optimize the process outcome, the effects of primary operation parameters such as
      the applied electric voltages and the liquid flow rates are studied systemically.
      In vitro drug release experiments are also carried out for the CES-produced MPs
      in comparison with those by a single axial electrospray process. Our experimental
      results show that the CES process can be effectively controlled to encapsulate
      drugs of low aqueous solubility for high encapsulation efficiency and optimal
      drug release profiles. 

PMID- 26208168
TI  - Impact of Anesthesia Protocols on In Vivo Bioluminescent Bacteria Imaging
      Results.
AB  - Infectious murine models greatly benefit from optical imaging using
      bioluminescent bacteria to non-invasively and repeatedly follow in vivo bacterial
      infection. In this context, one of the most critical parameters is the
      bioluminescence sensitivity to reliably detect the smallest number of bacteria.
      Another critical point is the anesthetic approaches that have been demonstrated
      to impact the bioluminescence flux emission in studies with luciferase
      transfected tumor cells. However, this impact has never been assessed on bacteria
      bioluminescent models. To this end, we investigated the effects of four
      anesthesia protocols on the bioluminescence flux in a central venous catheter
      murine model (SKH1-hr(hr) mice) infected by a bioluminescent S. aureus Xen36
      strain. Bioluminescence imaging was performed on mice anesthetized by either
      ketamine/xylazine (with or without oxygen supplementation), or isoflurane carried
      with air or oxygen. Total flux emission was determined in vivo daily for 3 days
      and ex vivo at the end of the study together with a CFU counting of the biofilm
      in the catheter. Bioluminescence flux differences appear between the different
      anesthetic protocols. Using a ketamine/xylazine anesthesia (with air), bacteria
      detection was impossible since the bioluminescence signal remains in the
      background signal. Mice anesthetized with isoflurane and oxygen led to a signal
      significantly higher to the background all along the kinetics. The use of
      isoflurane in air presents a bioluminescence signal similar to the use of
      ketamine/xylazine with oxygen. These data highlight the importance of oxygen to
      improve bioluminescence flux by bacteria with isoflurane as well as with
      ketamine/xylazine anesthetics. As a conclusion, we recommend the use of
      isoflurane anesthetic with oxygen to increase the bioluminescence sensitivity in
      this kind of study.

PMID- 26208169
TI  - Epidemiology and Risk Factors of Functional Constipation in Pregnant Women.
AB  - AIM: To understand the prevalence of functional constipation in pregnant women
      and to analyze the impact of its risk factors. METHODS: We searched hospital
      databases for women who were 37-41 weeks pregnant (1698 cases) from July 2012 to
      January 2014 in four hospitals in Shanghai. We reviewed factors including general
      data, living and eating habits, psychological history, past history of defecation
      in the 6 months before pregnancy and defecation after pregnancy. Data were
      analyzed using SPSS software. RESULTS: Pregnant women who were more than 35 years
      old, with a pre-pregnancy body mass index >24, who were highly educated and
      employed in a sedentary occupation, showed a higher prevalence of functional
      constipation. Multivariate logistic regression analysis indicated that the
      prevalence of functional constipation among pregnant women was related to age,
      pre-pregnancy body mass index, diet, exercise, occupation, psychological factors,
      threatened abortion in early pregnancy and constipation history. CONCLUSION: The
      prevalence rate of functional constipation in pregnant women was significantly
      higher than in the general population.

PMID- 26208171
TI  - High catalytic activity of palladium nanoparticle clusters supported on a
      spherical polymer network.
AB  - In this communication we report the synthesis of Pd nanoparticle clusters
      achieved via the assembly of Pd nanoparticles on the surface of a spherical
      polymer network. The network exhibits flexibility and adapts to the cluster
      formation. The nanoclusters display high catalytic activity toward p-nitrophenol
      reduction and the Suzuki-Miyaura coupling reaction. 

PMID- 26208170
TI  - Temporal Lobe and Frontal-Subcortical Dissociations in Non-Demented Parkinson's
      Disease with Verbal Memory Impairment.
AB  - OBJECTIVE: The current investigation examined verbal memory in idiopathic non
      dementia Parkinson's disease and the significance of the left entorhinal cortex
      and left entorhinal-retrosplenial region connections (via temporal cingulum) on
      memory impairment in Parkinson's disease. METHODS: Forty non-demented Parkinson's
      disease patients and forty non-Parkinson's disease controls completed two verbal
      memory tests--a wordlist measure (Philadelphia repeatable Verbal Memory Test) and
      a story measure (Logical Memory). All participants received T1-weighted and
      diffusion magnetic resonance imaging (3T; Siemens) sequences. Left entorhinal
      volume and left entorhinal-retrosplenial connectivity (temporal cingulum edge
      weight) were the primary imaging variables of interest with frontal lobe
      thickness and subcortical structure volumes as dissociating variables. RESULTS:
      Individuals with Parkinson's disease showed worse verbal memory, smaller
      entorhinal volumes, but did not differ in entorhinal-retrosplenial connectivity.
      For Parkinson's disease entorhinal-retrosplenial edge weight had the strongest
      associations with verbal memory. A subset of Parkinson's disease patients (23%)
      had deficits (z-scores < -1.5) across both memory measures. Relative to non
      impaired Parkinson's peers, this memory-impaired group had smaller entorhinal
      volumes. DISCUSSION: Although entorhinal cortex volume was significantly reduced
      in Parkinson's disease patients relative to non-Parkinson's peers, only white
      matter connections associated with the entorhinal cortex were significantly
      associated with verbal memory performance in our sample. There was also no
      suggestion of contribution from frontal-subcortical gray or frontal white matter
      regions. These findings argue for additional investigation into medial temporal
      lobe gray and white matter connectivity for understanding memory in Parkinson's
      disease.

PMID- 26208172
TI  - Simple and sensitive detection of aflatoxin B1 within five minute using a non
      conventional competitive immunosensing mode.
AB  - A novel competitive-type immunosensing strategy based on target-induced
      displacement reaction with antibody-functionalized mesoporous carbon (MSC)
      nanoparticles was designed for sensitive and rapid electrochemical detection of
      aflatoxin B1 (AFB1, used as a model) on the Nafion-functionalized sensing
      interface. Electroactive thionine molecules were initially decorated to the
      mesoporous carbon, and polyclonal anti-AFB1 antibody was then covalently
      conjugated to the nanostructures. The immunosensor was simply prepared via the
      electrostatic interaction between negatively charged Nafion film and positively
      charged anti-AFB1 antibody accompanying the nanostructures. The electrochemical
      signal originated from the carried thionine to mesoporous carbon. Upon target
      AFB1 introduction, the analyte reacted with the labeled anti-AFB1 antibody on the
      MSC based on specific antigen-antibody reaction and induced the dissociation of
      thionine-MSN nanostructures from the sensing interface, thus decreasing the
      cathodic current of the carried thionine molecules. Under optimal conditions, the
      immunosensor exhibited good electrochemical responses for determination of target
      AFB1 at a concentration as low as 3.0 pg mL(-1) (3.0 ppt). Importantly, the non
      conventional sensing system provides a promising immunosensing strategy for rapid
      screening of small molecules because of its simplicity, low cost and sensitivity
      without the needs of sample separation and washing step.

PMID- 26208173
TI  - Enhanced electrochemical recognition of double-stranded DNA by using
      hybridization chain reaction and positively charged gold nanoparticles.
AB  - Enhanced sequence-specific recognition of double-stranded DNA (dsDNA) was
      realized by using hybridization chain reaction (HCR) and positively charged gold
      nanoparticles ((+)AuNPs) dual signal amplification. To construct such a sensor,
      capture probe was initially assembled onto gold electrode surface. Upon addition
      of dsDNA, sandwiched DNA complex was formed between the capture probe and the
      detection probe, then another exposed part of the detection probe opened two
      alternating DNA hairpins (H1 and H2) in turn and initiated HCR to form a double
      helix. Meantime, (+)AuNPs were electrostatically adsorbed onto such double-helix
      to amplify the electrochemical signal. Upon optimal conditions, the electronic
      signals of ferrocene (Fc) that modified on H1 and H2 increased linearly with
      increasing dsDNA concentration over the range from 15 pM to 1.0 nM, with a
      detection limit of 2.6 pM. Moreover, the proposed method showed good sequence
      specificity for dsDNA recognition.

PMID- 26208174
TI  - A novel electrochemical aptasensor for ultrasensitive detection of kanamycin
      based on MWCNTs-HMIMPF6 and nanoporous PtTi alloy.
AB  - A novel aptasensor based on a novel composite film consisting of multi-walled
      carbon nanotubes (MWCNTs), ionic liquid (IL) of 1-hexyl-3-methylimidazolium
      hexafluorophosphate (HMIMPF6), and nanoporous PtTi (NP-PtTi) alloy was
      constructed for ultrasensitive detection of kanamycin. The NP-PtTi alloy was
      successfully fabricated by a simple dealloying of PtTiAl source alloy in HCl
      solution. The NP-PtTi alloy has uniform interconnected network structure with
      specific surface area and was used to immobilize aptamer. After modified with the
      composite material, current signal was amplified obviously, which attributed to
      the larger specific surface area and excellent electrical conductivity of NP-PtTi
      and MWCNTs. A number of factors affecting the activity of the aptasensor have
      been discussed and optimized. Under the optimized conditions, the proposed
      aptasensor provided a linear range of 0.05-100 ng mL(-1) with a low detection
      limit of 3.7 pg mL(-1). This aptasensor displayed high sensitivity, stability and
      reproducibility. In addition, the as-prepared aptasensor was successfully used
      for the determination of kanamycin in a real sample.

PMID- 26208175
TI  - Physical and Electrochemical Properties of PEDOT:PSS as a Tool for Controlling
      Cell Growth.
AB  - Conducting polymers are promising materials for tissue engineering applications,
      since they can both provide a biocompatible scaffold for physical support of
      living cells, and transmit electrical and mechanical stimuli thanks to their
      electrical conductivity and reversible doping. In this work, thin films of one of
      the most promising materials for bioelectronics applications, poly(3,4
      ethylenedioxythiophene) poly(styrenesulfonate) ( PEDOT: PSS), are prepared using
      two different techniques, spin coating and electrochemical polymerization, and
      their oxidation state is subsequently changed electrochemically with the
      application of an external bias. The electrochemical properties of these
      different types of PEDOT: PSS are studied through cyclic voltammetry and
      spectrophotometry to assess the effectiveness of the oxidation process and its
      stability over time. Their surface physical properties and their dependence on
      the redox state of PEDOT: PSS are investigated using atomic force microscopy
      (AFM), water contact angle goniometry and sheet resistance measurements. Finally,
      human glioblastoma multiforme cells (T98G) and primary human dermal fibroblasts
      (hDF) are cultured on PEDOT: PSS films with different oxidation states, finding
      that the effect of the substrate on the cell growth rate is strongly cell
      dependent: T98G growth is enhanced by the reduced samples, while hDF growth is
      more effective only on the oxidized substrates that show a strong chemical
      interaction with the cell culture medium.

PMID- 26208176
TI  - The contribution of temporary storage and executive processes to category
      learning.
AB  - Three distinctly different working memory processes, temporary storage, mental
      shifting and inhibition, were proposed to account for individual differences in
      category learning. A sample of 213 participants completed a classic category
      learning task and two working memory tasks that were experimentally manipulated
      for tapping specific working memory processes. Fixed-links models were used to
      decompose data of the category learning task into two independent components
      representing basic performance and improvement in performance in category
      learning. Processes of working memory were also represented by fixed-links
      models. In a next step the three working memory processes were linked to
      components of category learning. Results from modeling analyses indicated that
      temporary storage had a significant effect on basic performance and shifting had
      a moderate effect on improvement in performance. In contrast, inhibition showed
      no effect on any component of the category learning task. These results suggest
      that temporary storage and the shifting process play different roles in the
      course of acquiring new categories. 

PMID- 26208178
TI  - Point of care ultrasonography in haemophilia care: recommendations for training
      and competency evaluation.

PMID- 26208177
TI  - Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells
      for treating spinal cord injury: A human trial.
AB  - CONTEXT: Spinal cord injury (SCI) can cause irreversible damage to neural
      tissues. However, there is currently no effective treatment for SCI. The
      therapeutic potential of adipose-derived mesenchymal stem cells (ADMSCs) has been
      emerged. OBJECTIVE: We evaluated the effects and safety of the intrathecal
      transplantation of autologous ADMSCs in patients with SCI.
      Participants/Interventions: Fourteen patients with SCI were enrolled (12 for ASIA
      A, 1 for B, and 1 for D; duration of impairments 3-28 months). Six patients were
      injured at cervical, 1 at cervico-thoracic, 6 at thoracic, and 1 at lumbar level.
      Autologous ADMSCs were isolated from lipoaspirates of patients' subcutaneous fat
      tissue and 9 * 107 ADMSCs per patient were administered intrathecally through
      lumbar tapping. MRI, hematological parameters, electrophysiology studies, and
      ASIA motor/sensory scores were assessed before and after transplantation.
      RESULTS: ASIA motor scores were improved in 5 patients at 8 months follow-up (1-2
      grades at some myotomes). Voluntary anal contraction improvement was seen in 2
      patients. ASIA sensory score recovery was seen in 10, although degeneration was
      seen in 1. In somatosensory evoked potential test, one patient showed median
      nerve improvement. There was no interval change of MRI between baseline and 8
      months post-transplantation. Four adverse events were observed in three patients:
      urinary tract infection, headache, nausea, and vomiting. CONCLUSIONS: Over the 8
      months of follow-up, intrathecal transplantation of autologous ADMSCs for SCI was
      free of serious adverse events, and several patients showed mild improvements in
      neurological function. Patient selection, dosage, and delivery method of ADMSCs
      should be investigated further.

PMID- 26208179
TI  - Correction: The Crystal Structure and Small-Angle X-Ray Analysis of CsdL/TcdA
      Reveal a New tRNA Binding Motif in the MoeB/E1 Superfamily.

PMID- 26208182
TI  - Field study comparing the effect of hydraulic mixing on septic tank performance
      and sludge accumulation.
AB  - This study investigates the effect of hydraulic mixing on anaerobic digestion and
      sludge accumulation in a septic tank. The performance of a septic tank equipped
      with a hydraulic mixer was compared with that of a similar standard septic tank
      over a period of 10 months. The study was conducted in two phases: Phase-I--from
      May to November 2013 (6 months); Phase-II--from January to May 2014 (4 months).
      Hydraulic mixing effectively reduced the effluent biological oxygen demand (BOD)
      and total suspended solids, and reduced the sludge accumulation rate in the
      septic tank. The BOD removal efficiencies during Phase-II were 65% and 75% in the
      standard septic tank and a septic tank equipped with hydraulic mixer (Smart
      DigesterTM), respectively. The effect of hydraulic mixing reduced the rate of
      sludge accumulation from 0.64 cm/day to 0.27 cm/day, and increased the pump-out
      interval by a factor of 3.

PMID- 26208181
TI  - DNA Microarray Characterization of Pathogens Associated with Sexually Transmitted
      Diseases.
AB  - This study established a multiplex PCR-based microarray to detect simultaneously
      a diverse panel of 17 sexually transmitted diseases (STDs)-associated pathogens
      including Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium,
      Mycoplasma hominis, Ureaplasma, Herpes simplex virus (HSV) types 1 and 2, and
      Human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 35, 39, 54 and 58. The
      target genes are 16S rRNA gene for N. gonorrhoeae, M. genitalium, M. hominism,
      and Ureaplasma, the major outer membrane protein gene (ompA) for C. trachomatis,
      the glycoprotein B gene (gB) for HSV; and the L1 gene for HPV. A total of 34
      probes were selected for the microarray including 31 specific probes, one as
      positive control, one as negative control, and one as positional control probe
      for printing reference. The microarray is specific as the commensal and
      pathogenic microbes (and closely related organisms) in the genitourinary tract
      did not cross-react with the microarray probes. The microarray is 10 times more
      sensitive than that of the multiplex PCR. Among the 158 suspected HPV specimens
      examined, the microarray showed that 49 samples contained HPV, 21 samples
      contained Ureaplasma, 15 contained M. hominis, four contained C. trachomatis, and
      one contained N. gonorrhoeae. This work reports the development of the first high
      through-put detection system that identifies common pathogens associated with
      STDs from clinical samples, and paves the way for establishing a time-saving,
      accurate and high-throughput diagnostic tool for STDs. 

PMID- 26208183
TI  - Unstructured hexahedral mesh generation of complex vascular trees using a multi
      block grid-based approach.
AB  - The trend towards realistic numerical models of (pathologic) patient-specific
      vascular structures brings along larger computational domains and more complex
      geometries, increasing both the computation time and the operator time.
      Hexahedral grids effectively lower the computational run time and the required
      computational infrastructure, but at high cost in terms of operator time and
      minimal cell quality, especially when the computational analyses are targeting
      complex geometries such as aneurysm necks, severe stenoses and bifurcations.
      Moreover, such grids generally do not allow local refinements. As an attempt to
      overcome these limitations, a novel approach to hexahedral meshing is proposed in
      this paper, which combines the automated generation of multi-block structures
      with a grid-based method. The robustness of the novel approach is tested on
      common complex geometries, such as tree-like structures (including
      trifurcations), stenoses, and aneurysms. Additionally, the performance of the
      generated grid is assessed using two numerical examples. In the first example, a
      grid sensitivity analysis is performed for blood flow simulated in an abdominal
      mouse aorta and compared to tetrahedral grids with a prismatic boundary layer. In
      the second example, the fluid-structure interaction in a model of an aorta with
      aortic coarctation is simulated and the effect of local grid refinement is
      analyzed. 

PMID- 26208184
TI  - A new agenda for women's health in the Americas.

PMID- 26208185
TI  - Women's health in the Region of the Americas.

PMID- 26208186
TI  - Obstetric transition in the World Health Organization Multicountry Survey on
      Maternal and Newborn Health: exploring pathways for maternal mortality reduction.
AB  - OBJECTIVE: To test whether the proposed features of the Obstetric Transition
      Model-a theoretical framework that may explain gradual changes that countries
      experience as they eliminate avoidable maternal mortality-are observed in a
      large, multicountry, maternal and perinatal health database; and to discuss the
      dynamic process of maternal mortality reduction using this model as a theoretical
      framework. METHODS: This was a secondary analysis of a cross-sectional study by
      the World Health Organization that collected information on more than 300 000
      women who delivered in 359 health facilities in 29 countries in Africa, Asia,
      Latin America, and the Middle East, during a 2-4-month period in 2010-2011. The
      ratios of Potentially Life-Threatening Conditions, Severe Maternal Outcomes,
      Maternal Near Miss, and Maternal Death were estimated and stratified by stages of
      obstetric transition. The characteristics of each stage are defined. RESULTS:
      Data from 314 623 women showed that female fertility, indirectly estimated by
      parity, was higher in countries at a lower obstetric transition stage, ranging
      from a mean of 3 children in Stage II to 1.8 children in Stage IV. Medicalization
      increased with obstetric transition stage. In Stage IV, women had 2.4 times the
      cesarean deliveries (15.3% in Stage II and 36.7% in Stage IV) and 2.6 times the
      labor inductions (7.1% in Stage II and 18.8% in Stage IV) as women in Stage II.
      The mean age of primiparous women also increased with stage. The occurrence of
      uterine rupture had a decreasing trend, dropping by 5.2 times, from 178 to 34
      cases per 100 000 live births, as a country transitioned from Stage II to IV.
      CONCLUSIONS: This analysis supports the concept of obstetric transition using
      multicountry data. The Obstetric Transition Model could provide justification for
      customizing strategies for reducing maternal mortality according to a country's
      stage in the obstetric transition.

PMID- 26208187
TI  - [Alcohol consumption before and during pregnancy in Argentina: prevalence and
      risk factors].
AB  - OBJECTIVE: Describe alcohol consumption by Argentine women before and during
      pregnancy and identify the factors associated with consumption- and pregnancy
      related changes. METHODS: Cross-sectional observational study. Women were
      interviewed after giving birth and receiving care at two perinatal health care
      centers in Santa Fe, Argentina. Sociodemographic information, data on their
      alcohol use, and other information were obtained from the participants. A
      descriptive analysis of consumption prevalence rates was made and the factors
      associated with patterns of alcohol use were identified by means of repeated
      measure analysis. RESULTS: Of the 614 participants, 75.2% had had at least one
      alcoholic drink (standard unit) during pregnancy and 83.3% had done so in the
      previous year; 15.1% admitted having at least one episode of binge drinking (five
      or more drinks) during pregnancy and 27.6% in the year prior to pregnancy. Only
      30.6% of the women said they had made any change in consumption during the
      previous year; of those, 55.6% reduced their consumption and 41.8% stopped
      drinking. Women who consumed the most alcohol before and during pregnancy
      reported higher consumption by their partners, smoked, and had more permissive
      attitudes about alcohol use during pregnancy. CONCLUSIONS: A specific prevention
      plan is required in Argentina to reduce alcohol use in pregnant women, adjusted
      to local patterns of use, with interventions that include couples, and focused on
      the youngest women, those who use tobacco, and those who have more permissive
      attitudes about alcohol use.

PMID- 26208188
TI  - [Maternal deaths in Belo Horizonte, Brazil: perceptions of quality of care and
      preventability].
AB  - OBJECTIVE: To analyze maternal deaths in Belo Horizonte from 2003 to 2010 based
      on the perception of family members of women who died from pregnancy-related
      causes. METHODS: Maternal deaths were researched at the City of Belo Horizonte
      Department of Health's Maternal, Fetal, and Infant Death Prevention Committee.
      Family members of deceased women were recruited by telephone or personally.
      Sample size was not pre-defined; rather, a saturation criterion was employed.
      Nevertheless, an attempt was made to include families of women who received both
      public and private health care. The interviews focused on health history prior to
      the pregnancy; clinical history in the period from the start of pre-natal care
      until death; care received by the deceased women before, during and after
      delivery. After transcription and analysis of all interviews, the NVivo 9
      qualitative analysis software was used to categorize and code the interviews.
      RESULTS: The family members of 11 women were interviewed. The victims were
      between 16 and 40 years old, died of various causes, and had various occupations.
      Most were in their first or second pregnancy, and most relied on public health
      care. Seven women had between 8 and 11 years of schooling, and seven were single.
      Ten women were white or brown. All the family members interviewed were female,
      with age ranging from 18 to 66 years. Most were the mothers of the deceased
      women, had little schooling, were married and worked in the home. The
      interviewees reported difficulties with the care received during the pregnancy,
      with little attention paid to the clinical status of the pregnant women. Nine
      deaths occurred after the delivery. CONCLUSIONS: According to the reports of
      family members, the maternal deaths recorded in Belo Horizonte between 2003 and
      2010 were associated with issues that were possibly preventable, relating to the
      reproductive rights of women, to pregnancy, delivery, and perinatal care.

PMID- 26208189
TI  - [Trend in mortality from external causes in pregnant and postpartum women and its
      relationship to socioeconomic factors in Colombia, 1998-2010].
AB  - OBJECTIVE: Determine the trend in mortality from external causes in pregnant and
      postpartum women and its relationship to socioeconomic factors. METHODS:
      Descriptive study, based on the official registries of deaths reported by the
      National Statistics Agency, 1998-2010. The trend was analyzed using Poisson
      regressions. Bivariate correlations and multiple linear regression models were
      constructed to explore the relationship between mortality and socioeconomic
      factors: human development index, Gini index, gross domestic product, unsatisfied
      basic needs, unemployment rate, poverty, extreme poverty, quality of life index,
      illiteracy rate, and percentage of affiliation to the Social Security System.
      RESULTS: A total of 2 223 female deaths from external causes were recorded, of
      which 1 429 occurred during pregnancy and 794 in the postpartum period. The gross
      mortality rate dropped from 30.7 per 100 000 live births plus fetal deaths in
      1998 to 16.7 in 2010. A downward curve with no significant inflection points was
      shown in the risk of dying from this cause. The multiple linear regression model
      showed a correlation between mortality and extreme poverty and the illiteracy
      rate, suggesting that these indicators could explain 89.4% of the change in
      mortality from external causes in pregnant and postpartum women each year in
      Colombia. CONCLUSIONS: Mortality from external causes in pregnant and postpartum
      women showed a significant downward trend that may be explained by important
      socioeconomic changes in the country, including a decrease in extreme poverty and
      in the illiteracy rate.

PMID- 26208190
TI  - Maternal near miss among women using the public health system in the Amazon and
      Northeast regions of Brazil.
AB  - OBJECTIVE: To assess the prevalence of pregnancy complications identified as
      maternal near miss (MNM) and associated factors among women using the public
      health care system in the Amazon and Northeast regions of Brazil. METHODS: A
      secondary analysis of a population-based survey conducted in 2010 was performed
      focusing on women self-reporting maternal complications. The main outcome was
      MNM, pragmatically defined as intensive care unit admission, eclampsia,
      hysterectomy, or blood transfusion. In addition, the risk of MNM was estimated
      for certain sociodemographics and characteristics of care received. Poisson
      regression was performed, generating adjusted prevalence ratios (PRadj) with 95%
      confidence intervals (95%CI). RESULTS: A total of 13 044 women (77%) who had
      given birth during the prior year using the public health system were
      interviewed. At least one complication was reported by 37.5%, with hemorrhage
      (28.4%) and infection (8.3%) being the most frequent. The overall MNM ratio was
      31.5 per 1 000 live births, higher for the Amazon region than for the Northeast.
      Factors with a higher risk for developing MNM were: indigenous ethnicity (PRadj
      2.77; 95% CI: 1.50-5.14), more than one hour to reach the hospital (PRadj 1.55;
      95%CI: 1.06-2.25), being refused by a full hospital and having to find another
      one (PRadj 1.49; 95%CI: 1.03-2.16), cesarean section (PRadj 2.56; 95%CI: 1.90
      3.44), and public prenatal care (PRadj 1.95; 95%CI: 1.06-3.61). CONCLUSIONS:
      Users of public health system in the Amazon and Northeast regions of Brazil have
      high MNM rates. Some characteristics of the women and of the care they received
      represent inequalities associated with higher risk for MNM. Specific actions are
      required to improve maternal health programs in these expansive areas of the
      country.

PMID- 26208191
TI  - [Inequalities and sociodemographic characteristics of maternal mortality in La
      Guajira, Colombia, 2010-2012].
AB  - OBJECTIVE: Identify the inequalities and sociodemographic characteristics that
      negatively affect maternal mortality in the department of La Guajira, Colombia.
      METHODS: A descriptive study was conducted in which cases of maternal deaths in
      the department of La Guajira between 2010 and 2012 were analyzed, based on data
      from secondary sources. The difference in rates, rate ratio, population
      attributable risk percent, and Gini and concentration coefficients were
      calculated. RESULTS: 54 maternal deaths were recorded, 61.1% of which were
      indigenous and 16.7% Afro-Colombians; the majority did not have any schooling
      (33.3%) or only primary schooling (29.6%). Inequalities in the difference of
      rates, rate ratio, and population attributable risk percent were calculated for
      La Guajira and other departments in the Caribbean region and in Colombia;
      however, the differences were not reflected in the Gini and concentration
      coefficients. CONCLUSIONS: Maternal mortality was significantly higher in
      indigenous women than in non-indigenous women. Sexual and reproductive health
      programs should be strengthened and maternal health policies improved through a
      multicultural approach to eliminate or reduce inequalities related to maternal
      mortality in this population.

PMID- 26208192
TI  - "Siempre me critican": barriers to reproductive health in Ocotal, Nicaragua.
AB  - OBJECTIVE: To identify perceived barriers to accessing reproductive health care
      according to the women of Ocotal, Nicaragua; describe their understanding of
      their reproductive rights; and document their opinions about Nicaragua's total
      ban on abortion. METHODS: From May to June 2014, three focus group discussions
      were held in Spanish with 17 women from two different neighborhoods (barrios) in
      the city of Ocotal, Nicaragua. A semi-structured discussion guide with open-ended
      questions was employed to elucidate local perspectives regarding the focus group
      discussions themes. RESULTS: Serious obstacles including 1) violence against
      women, 2) machismo, 3) criticism from others, and 4) lack of communication and
      education limit women's ability to make their own reproductive health decisions.
      Women had a pervasive lack of knowledge about reproductive rights and the
      international human rights documents that define them. In addition, due to
      religious and cultural ideologies, most women supported the country's total ban
      on abortion in most circumstances, with the possible exception of rape.
      CONCLUSIONS: Both men and women in Ocotal should be encouraged to participate in
      community-level programs designed to reduce the impact of the following obstacles
      to receiving reproductive health care: 1) violence against women and machismo; 2)
      insufficient, non-standardized sexual education and information about
      reproductive rights; and 3) poor communication within families and the community
      at large. Any future public health campaigns to address women's reproductive
      health needs in Ocotal should implement these types of programs, at the
      neighborhood level, to reduce stigma surrounding sexual health and activity.

PMID- 26208193
TI  - [Corrected estimates of femicides in Brazil, 2009 to 2011].
AB  - OBJECTIVE: To estimate the corrected femicide rates and to describe the
      characteristics of these deaths in Brazil during the 2009-2011 triennium.
      METHODS: A descriptive study was performed with data from the Brazilian Mortality
      Information System. Femicides were defined as all female deaths classified in the
      Assault chapter of ICD-10 (X85-Y09). These data underwent two correction
      procedures: proportional redistribution of events of undetermined intent (Y10
      Y34) and application of correction factors for mortality rates previously
      described in the literature. RESULTS: During the period analyzed, 13 071
      femicides were recorded in the Mortality Information System. After the first
      correction procedure, 17 167 femicides were estimated, corresponding to a death
      rate of 5.86 per 100 000 women. Higher femicide rates were recorded in the
      Northeast, Midwest and North regions of Brazil (6.93, 6.88 and 6.43 deaths per
      100 000 women respectively) vs. 5.07 and 5.09 per 100 000 women in the South and
      Southeast respectively. Of the victims, 29.7% were between 20 and 29 years of age
      and 60.9% were black. Among women aged 15 years or older, 48% had schooling of
      not more than 8 years. Fire guns were used in 50.2% of deaths; 27.6% of deaths
      took place in the household; and 35.1% took place on weekends. CONCLUSIONS:
      Femicide death rates were high and support the need for correction to reduce
      underestimation. The victims were women of all age groups, ethnicities, and
      schooling levels. However, most victims were young, black, with low schooling,
      living in the Northeast, Midwest, and North of Brazil.

PMID- 26208194
TI  - [Under the shadow of maternity: pregnancy, suicidal ideation, and intimate
      partner violence].
AB  - OBJECTIVE: To investigate the association between intimate partner violence and
      indicators of suicidal ideation during the current pregnancy. METHODS: This is a
      cross-sectional observational study developed with 358 pregnant women selected by
      systematic random sampling in Ribeirao Preto, southeastern Brazil. The Back
      Suicidal Ideation Scale and an adapted version of the instrument used in the
      World Health Organization Multi-country Study on Women's Health and Domestic
      Violence were used to identify indicators of suicidal ideation and psychological,
      physical, and sexual acts of intimate partner violence during the current
      pregnancy. Multiple logistic regression was used to obtain adjusted prevalence
      odds ratios with a 95% confidence interval. RESULTS: The prevalence of indicators
      of suicidal ideation was 7.8%. Of the participants, 17.6% reported some type of
      intimate partner violence during the current pregnancy. Among these, 95.2%
      reported having suffered psychological violence, 36.5% physical violence, and
      1.6% sexual violence. Multiple logistic regression analysis showed that women
      exposed to violence were 6.29 times more likely to have indicators of suicidal
      ideation. CONCLUSIONS: Policy makers and health care providers must be made aware
      of the impact of intimate partner violence, including in terms of suicidal
      ideation, especially during pregnancy. The adoption of simple measures, such as
      the scales used in the present study, may provide information regarding the
      extent of intimate partner violence and suicidal ideation in health care
      services.

PMID- 26208195
TI  - [Domestic violence as a threat to maternal and child well-being in an urban
      migrant community in Peru].
AB  - OBJECTIVE: To examine the impact that domestic violence (DV) has on hindering the
      success of urban migrants in Peru and any association with maternal depression,
      impaired parenting, social capital, and child development. METHODS: This was a
      cross-sectional study consisting of structured interviews with 97 mothers and
      their school-aged children in El Porvenir, a predominantly migrant area of the
      city of Trujillo, Peru. Data collection occurred in February-June 2011. Proven
      tools previously validated for use in Spanish were used to assess the following
      variables: maternal depression, social capital, domestic violence, parenting
      behaviors, child socioemotional development, and child cognitive development.
      Correlational, multiple regression, tests of interaction, and indirect/mediator
      models were used for analysis. RESULTS: Sixty-five percent of women reported
      currently experiencing DV. DV strongly predicted depression (P < 0.001). Women
      who reported DV were less likely to be employed (P < 0.05), had lower cognitive
      social capital (P < 0.01), engaged in fewer caregiving activities (P < 0.05), had
      less maternal energy (P < 0.05), and were less warm (P < 0.05). DV was associated
      with internalizing behaviors in children (P < 0.01), with impaired parenting
      partially mediating this relationship. CONCLUSIONS: DV compromises women's mental
      health and parenting ability. High rates of DV among urban migrants affect the
      whole community by hindering employment potential and reducing trust among
      community members. Interventions targeting DV-related variables (e.g., substance
      abuse and limited job opportunities for men) could reduce the deleterious effects
      of DV on urban migrant communities across Latin America.

PMID- 26208196
TI  - [Sexual violence: narratives of women with mental disorders in Brazil].
AB  - OBJECTIVES: To understand the impact of sexual violence suffered by women with
      mental disorders based on self-reports of these experiences. METHODS: The reports
      emerged from open interviews with women receiving care at public mental health
      services in the states of Minas Gerais and Rio de Janeiro, Brazil. These
      interviews were part of a larger research project that had the overall objective
      of investigating how this population group lives and thinks sexuality, in order
      to contribute to actions to promote sexual health. Data collection took place in
      2008. RESULTS: Seventeen women with age between 18 and 68 years were interviewed.
      Fourteen reported having had stable relationships, but only three were still in
      these relationships. Most of the stable relationships had not been formalized
      into marriage. Two participants were widows and 13 had children. All the
      participants reported difficulties in living with their partners and children and
      having few friends and little family support. The instability of relationships
      was attributed to situations of aggression, infidelity, and use of drugs and
      alcohol. Seven women reported having been victims of physical violence within the
      family, mostly from partners. Two participants reported never having had sexual
      relations. CONCLUSIONS: Health care professionals must be trained to encourage
      the report of sexual violence by women and adequately handle the situation.
      Intersectoral actions to deal with this issue are also essential.

PMID- 26208197
TI  - [Trends in mortality by assault in women in selected countries of Latin America,
      2001-2011].
AB  - OBJECTIVE: Describe the trend in deaths by assault in women in Argentina, Brazil,
      Chile, Colombia, and Mexico between 2001 and 2011. METHODS: Descriptive study.
      Mortality from assaults and undetermined intentional acts was calculated,
      adjusted for age, using the direct method and the World Health Organization's
      standard population. Joinpoint regression models were used to identify
      statistically significant changes. The male:female mortality ratio was compared
      and trends in the rates were calculated and adjusted for each of the two causes
      of death and the specific rates of mortality by assault in women by age group.
      RESULTS: The highest rates of assault of women were reported in Brazil, followed
      by Colombia, Mexico, Argentina, and Chile. Between 2001 and 2011, decreases were
      reported from Argentina and Colombia; in Brazil and Mexico the rates increased;
      and in Chile they remained stable. The highest specific rates were found in young
      women (15-29 years) and adults (30-44 and 45-59 years). In Colombia the rates
      declined in all groups, while in Mexico they increased in women aged 15 to 59
      years. Only Colombia showed a decrease in mortality from undetermined intentional
      acts; in Argentina and Mexico there was a decrease at the beginning of the period
      with a later increase; in Brazil no variations were observed. CONCLUSIONS:
      Mortality from assaults on women in Brazil, Colombia, and Mexico between 2001 and
      2011 was higher than the world average and the Latin American average; rates were
      lower in Argentina and Chile, with minor differences between the sexes. Progress
      must be made in terms of understanding the power relationships that underlie
      femicide, which should be included in national criminal legislation.

PMID- 26208198
TI  - [HIV and violence against women: study in a municipality with high prevalence of
      Aids in the South of Brazil].
AB  - OBJECTIVE: To investigate the prevalence and factors associated with violence
      against women with HIV in a mid-sized city in the South of Brazil. METHODS: This
      cross-sectional study included 161 users of an HIV Specialized Care Service in a
      city with high prevalence of Aids in the state of Rio Grande do Sul. To determine
      the prevalence and forms of violence, 13 questions of the World Health
      Organization Violence Against Women (WHO VAW) instrument, adapted and validated
      for Brazilian Portuguese, were used. The presence of lifetime psychological,
      physical, and sexual violence perpetrated by intimate partners or former
      partners, family members, acquaintances, friends, neighbors, colleagues, or
      strangers was investigated. Statistical analysis employed the chi-square test and
      Poisson multiple regression. RESULTS: Psychological violence was reported by 117
      women (72.7%), physical violence by 88 women (54.6%), and sexual violence by 41
      women (25.4%). The adjusted prevalence of violence was 11.5 times higher in women
      living with HIV for more than 5 years as compared to those living with HIV for <
      5 years; 9.5 times higher in those with more than three children vs. three or
      fewer children; and 7.2 times higher in those who had sex before before the age
      of 15 years vs. at 15 years of age or older (P < 0.01). CONCLUSIONS: The
      frequency of all types of violence was high in this group of women with HIV.
      Health care professionals should understand and address issues relating to
      prejudice and provide comprehensive care, asking about the presence of violence
      in the life of women.

PMID- 26208199
TI  - [The gender gap in domestic violence in older adults in Latin America: the IMIAS
      Study].
AB  - OBJECTIVE: Describe the prevalence of domestic violence in older men and women in
      Natal, Brazil, and Manizales, Colombia and explore whether the differences by
      gender are due to lifetime differences in social and financial status. METHODS:
      Cross-sectional study with a random sampling of 802 men and women in the IMIAS
      Study (International Mobility in Aging Study) (65-74 years old) conducted in
      Natal (Brazil) and Manizales (Colombia). Incidents that occurred in the last six
      months and any time during their lives were evaluated using the HITS scale.
      Poisson regression was used to estimate the reasons for the prevalence of
      violence against women by men. RESULTS: Experience of physical violence occurring
      any time in life ranged from 2.2% to 18.3%, depending on the city and the sex.
      Psychological violence was higher in women: violence perpetrated by partners
      affected 25.7% of women in Natal and 19.4% in Manizales; and by the family, 18.3%
      in Manizales and 10% in Natal. Almost half of the participants reported suffering
      psychological violence at some time during their life. Experience of current
      violence or at some time during life was most frequent in women, even after
      adjustment for co-variables, with prevalence ratios of 1.60 to 2.14. CONCLUSIONS:
      The rates of prevalence of domestic violence in older adults show that women are
      more affected, which means that they should be considered a priority in the
      prevention policies on Latin America's health agenda.

PMID- 26208200
TI  - [Psychosocial risk factors and work satisfaction in female seasonal workers in
      Chile].
AB  - OBJECTIVE: Characterize the relationship between psychosocial risk factors and
      work satisfaction in female seasonal agricultural workers in central Chile.
      METHODS: Cross-sectional study in a non-probability sample of 106 female workers
      for a fruit trading and export company in the region of Maule, Chile. The
      interviews were conducted in September and October 2013. The SUSESO ISTA-21
      questionnaire was used to evaluate five areas of psychosocial risk in the
      workplace (psychological requirements, active work and opportunities for
      development, social support in the company and quality of leadership,
      compensation, and "double presence"). Questionnaire S10/12 was used to measure
      labor satisfaction in three areas (satisfaction with benefits received,
      satisfaction with the company's physical environment, and satisfaction with
      supervision) and satisfaction in general. RESULTS: The level of psychosocial risk
      was high in two areas (double presence, and active work and possibilities of
      development) and medium in the other areas; the level of satisfaction was high in
      all three areas. The perception of psychosocial risk factors was negatively
      associated with work satisfaction in three areas: active work and opportunities
      for development, social support in the company and quality of leadership, and
      compensation (compensation was negatively associated except for satisfaction with
      the company's physical environment). CONCLUSIONS: Risks associated with seasonal
      work and the main issues that workers consider to affect their satisfaction with
      work and, by extension, their general well-being, are concentrated mainly in the
      three areas identified.

PMID- 26208201
TI  - Childhood trauma is associated with depressive symptoms in Mexico City women.
AB  - OBJECTIVE: To describe childhood trauma and depressive symptoms in Mexican women
      and to explore the relationships between number and type of childhood traumatic
      events and depressive symptoms. METHODS: A community-based sample of 100 women
      was interviewed using a demographic questionnaire, the Life Stressor Checklist
      Revised (LSC-R), and the Center for Epidemiologic Studies Depression Scale (CES
      D). Childhood trauma (trauma at or before 16 years of age) and depressive
      symptoms were described, and logistic and linear regressions were used to analyze
      the relationship between childhood traumatic events and current depressive
      symptoms. RESULTS: Participants reported a mean of 9.46 (standard deviation (SD):
      4.18) lifetime traumas and 2.76 (SD: 2.34) childhood traumas. The mean CES-D
      score was 18.9 (SD: 12.0) and 36.0% of participants had clinically significant
      depression (CES-D > 24). Depression scores were correlated with lifetime trauma,
      childhood trauma, education level, employment status, and number of self-reported
      current medical conditions. Depression scores were not significantly correlated
      with age, marital status, number of children, or socioeconomic status. For every
      additional childhood trauma experienced, the odds of clinically significant
      depressive symptoms (CES-D > 24) increased by 50.0% (adjusted odds ratio (OR):
      1.50; 95% confidence interval: 1.14-1.96), after controlling for number of
      children, age, education level, employment status, and number of self-reported
      medical conditions. CONCLUSIONS: The results indicated that the number of
      childhood trauma exposures is associated with current depression among urban
      Mexican women, suggesting a need for trauma-informed care in this setting.

PMID- 26208202
TI  - Soccer and sexual health education: a promising approach for reducing adolescent
      births in Haiti.
AB  - OBJECTIVE: To explore the effect of an innovative, integrative program in female
      sexual reproductive health (SRH) and soccer (or futbol, in Haitian Creole) in
      rural Haiti by measuring the rate of births among program participants 15-19
      years old and their nonparticipant peers. METHODS: A retrospective cohort study
      using 2006-2009 data from the computerized data-tracking system of the Haitian
      Health Foundation (HHF), a U.S.-based nongovernmental organization serving urban
      and rural populations in Haiti, was used to assess births among girls 15-19 years
      old who participated in HHF's GenNext program, a combination education-soccer
      program for youth, based on SRH classes HHF nurses and community workers had been
      conducting in Haiti for mothers, fathers, and youth; girl-centered health
      screenings; and an all-female summer soccer league, during 2006-2009 (n = 4 251).
      Bivariate and multiple logistic regression analyses were carried out to assess
      differences in the rate of births among program participants according to their
      level of participation (SRH component only ("EDU") versus both the SRH and soccer
      components ("SO") compared to their village peers who did not participate. Hazard
      ratios (HRs) of birth rates were estimated using Cox regression analysis of
      childbearing data for the three different groups. RESULTS: In the multiple
      logistic regression analysis, only the girls in the "EDU" group had significantly
      fewer births than the nonparticipants after adjusting for confounders (odds ratio
      = 0.535; 95% confidence interval (CI) = 0.304, 0.940). The Cox regression
      analysis demonstrated that those in the EDU group (HR = 0.893; 95% CI = 0.802,
      0.994) and to a greater degree those in the SO group (HR = 0.631; 95% CI = 0.558,
      0.714) were significantly protected against childbearing between the ages of 15
      and 19 years. CONCLUSIONS: HHF's GenNext program demonstrates the effectiveness
      of utilizing nurse educators, community mobilization, and youth participation in
      sports, education, and structured youth groups to promote and sustain health for
      adolescent girls and young women.

PMID- 26208203
TI  - [HIV infection in female adolescents: a qualitative study].
AB  - OBJECTIVE: To investigate the vulnerabilities that favor HIV infection by female
      adolescents and young adults and to determine the difficulties faced by this
      population following diagnosis. METHODS: For this qualitative study we
      interviewed HIV-seropositive young or adolescent women diagnosed as adolescents
      and receiving treatment at the time of the interviews. The interviews were audio
      recorded and entirely transcribed. The data obtained were analyzed through
      intensive reading, classification of themes, and hermeneutic dialectic analysis
      in dialogue with the literature. RESULTS: Twenty-three women diagnosed between 11
      and 19 years of age were interviewed. Twenty-one participants had acquired Aids
      via sexual transmission and one from blood. Transmission mode was unknown in one
      case. The interviews revealed the following vulnerability situations: disbelief
      in the possibility of contamination, young age at sexual initiation (below the
      Brazilian national average), not using a condom, having promiscuous partners or
      partners who used injectable drugs, and submitting to violence. The main problems
      faced after the diagnosis were prejudice, discrimination, need to take medication
      daily, and concerns associated with the desire of becoming a mother. CONCLUSIONS:
      Reducing the feminization of Aids entails enhancing the debate regarding
      sexuality and the dilemmas faced by adolescents to establish an open and
      unprejudiced dialogue that is not biased by norms, in addition to providing
      guidance about sexually transmitted diseases, with free and uncomplicated
      distribution of condoms.

PMID- 26208204
TI  - [Trends in mortality from breast cancer in Cordoba, Argentina, 1986-2011: some
      socio-historical interpretations].
AB  - OBJECTIVE: Analyze and interpret trends in mortality from breast cancer in recent
      decades in the province of Cordoba, Argentina, relative to demographic changes
      and the sociopolitical context. METHODS: Raw, standardized (direct method), and
      age-specific mortality from breast cancer was calculated for 1986-2011 in
      Cordoba. Using RiskDiff(r) software, variations in the 1986 to 2011 raw rates
      were analyzed. Joinpoint regression models were adjusted to standardized and
      specific rates by age group. Secondary data sources (laws, decrees, health
      programs) were consulted for information on the sociopolitical context of the
      period. RESULTS: Raw mortality due to breast cancer increased 24.97% from 1986 to
      2011, an increase that can be attributed to the increase in the risk of dying
      (5.22%), to structural changes (19.75%), and to population size (39.66%).
      Standardized mortality from breast cancer shows a rising trend up to 1996 (annual
      percentage change [APC] = 1.62%; P <0.05), and then begins to decline (APC = 
      2.1%; P <0.05), slowing around the year 2001. For socio-historical
      interpretations, the analysis focused on demographic, epidemiological, and health
      related changes, as well as the socioeconomic and political events of the period
      studied. CONCLUSIONS: The behavior of mortality from breast cancer in this period
      is associated with contextual factors (demographic, historical, economic, and
      political). The results of this study will help define actions and policies in
      breast cancer and women's health care.

PMID- 26208205
TI  - [Obesity in Brazilian women: association with parity and socioeconomic status].
AB  - OBJECTIVE: To determine the influence of reproductive history on the prevalence
      of obesity in Brazilian women and the possible modifying effect of socioeconomic
      variables on the association between parity and excess weight. METHODS: A
      retrospective analysis of complex sample data collected as part of the 2006
      Brazilian National Survey on Demography and Health, which included a group
      representative of women of childbearing age in Brazil was conducted. The study
      included 11 961 women aged 20 to 49 years. The association between the study
      factor (parity) and the outcome of interest (obesity) was tested using logistic
      regression analysis. The adjusted effect of parity on obesity was assessed in a
      multiple regression model containing control variables: age, family purchasing
      power, as defined by the Brazilian Association of Research Enterprises (ABEP),
      schooling, and health care. Significance level was set at below 0.05. RESULTS:
      The prevalence of obesity in the study population was 18.6%. The effect of parity
      on obesity was significant (P for trend < 0.001). Unadjusted analysis showed a
      positive association of obesity with parity and age. Family purchase power had a
      significant odds ratio for obesity only in the unadjusted analysis. In the
      adjusted model, this variable did not explain obesity. CONCLUSIONS: The present
      findings suggest that parity has an influence on obesity in Brazilian women of
      childbearing age, with higher prevalence in women vs. without children.

PMID- 26208206
TI  - Assessment of provider competence and quality of maternal/newborn care in
      selected Latin American and Caribbean countries.
AB  - OBJECTIVE: To obtain a snapshot of the maternal and newborn care provided by
      different types of maternal and child health providers in Latin America and the
      Caribbean (LAC) to 1) better inform advocacy and programmatic strategies and
      interventions to improve the quality of those services in the region, and 2)
      determine the need for more rigorous study of the issues. METHODS: A rapid
      assessment of 83 health workers providing antepartum, intrapartum, and immediate
      postpartum and newborn care (within two hours of birth) in eight LAC countries
      was conducted in November and December of 2011. Health workers were observed by
      two-person expert maternal/newborn clinician teams using pretested forms based on
      international quality-of-care standards. A total of 105 care encounters were
      observed, primarily in urban, public, referral-level settings. Providers of care
      included obstetricians, midwives, generalist physicians, medical residents,
      registered nurses, auxiliary nurses, and students of medicine, midwifery, and
      nursing. RESULTS: Hand washing, as an indicator of quality of antepartum care,
      was observed in only 41% of the observed encounters. Labor management often
      lacked certain elements of respectful maternity care across all provider groups.
      Several clinical tasks of high importance in the identification and prevention of
      common complications of antepartum, intrapartum, and immediate postpartum/newborn
      care were not documented as performed during the observation periods. Providers
      self-reported limited competence (ability to perform to a defined level of
      proficiency) in manual removal of the placenta, bimanual compression of the
      uterus, and newborn resuscitation. CONCLUSIONS: The findings suggest that 1) the
      quality of maternal and newborn care and 2) the competence of maternal and child
      health providers in the diverse selection of LAC countries that were studied
      require substantial attention.

PMID- 26208207
TI  - [Model for a comprehensive approach to maternal mortality and severe maternal
      morbidity].
AB  - Maternal mortality is an important public health and human rights problem and
      reflects the effects of social determinants on women's health. Understanding the
      extent and causes of maternal death has been insufficient to achieve the
      Millennium Development Goals. This article proposes a model for a comprehensive
      approach to maternal mortality, covering seven areas: prioritization and
      definition of the problem, contextual description, methodological scope,
      knowledge management, innovation, implementation, and a monitoring and evaluation
      system. This model helps address problems associated with maternal mortality and
      severe maternal morbidity through early monitoring of potentially fatal
      complications in the reproductive process. Knowledge management is important for
      the reorientation of policies, programs, and health care. Interaction and
      synergies among people, communities, and actors in the health system should be
      strengthened in order to improve the results of health programs. More validated
      scientific information is needed on how actions should be implemented in
      different environments. It is essential to strengthen communication among
      research centers, cooperation agencies, and government organizations and to
      include them in programs and in the definition of a new women's health agenda in
      the Region of the Americas. 

PMID- 26208208
TI  - [Enforceability of the right to health protection in obstetric services in
      Mexico].
AB  - The inclusion of the framework of human rights in maternal health is mentioned
      more and more frequently as a feasible proposal to improve the care that women
      receive in obstetric health care services. Despite the fact Mexico has a solid
      regulatory framework for obstetric care, mechanisms of enforceability are
      essential to ensure that health-related human rights are upheld. In addition to
      being in place, enforceability mechanisms should be effective and accessible to
      people, particularly in obstetric care, where repeated human rights violations
      occur that endanger women's health and lives. The objective of this article is to
      specify the regulatory, legal, and extralegal elements that need to be considered
      in order to include maternal health in a set of enforceable human rights. 

PMID- 26208209
TI  - [Inclusion of traditional birth attendants in the public health care system in
      Brazil: reflecting on challenges].
AB  - The present article describes an experience with traditional birth attendants
      carried out in the state of Tocantins, Brazil, between 2010 and 2014. The
      experience was part of a diagnostic project to survey home deliveries in the
      state of Tocantins and set up a registry of traditional birth attendants for the
      Health Ministry's Working with Traditional Birth Attendants Program (PTPT). The
      project aimed to articulate the home deliveries performed by traditional birth
      attendants to the local health care systems (SUS). Sixty-seven active traditional
      birth attendants were identified in the state of Tocantins, and 41 (39
      indigenous) participated in workshops. During these workshops, they discussed
      their realities, difficulties, and solutions in the context of daily adversities.
      Birth attendants were also trained in the use of biomedical tools and neonatal
      resuscitation. Based on these experiences, the question came up regarding the
      true effectiveness of the strategy to include traditional birth attendants in the
      SUS. The present article discusses this theme with support from the relevant
      literature. The dearth of systematic studies focusing on the impact of PTPT
      actions on the routine of traditional birth attendants, including perinatal
      outcomes and remodeling of health practices in rural, riverfront, former slave,
      forest, and indigenous communities, translates into a major gap in terms of the
      knowledge regarding the effectiveness of such initiatives. 

PMID- 26208210
TI  - Disease-modifying strategies for Parkinson's disease.
AB  - Parkinson's disease (PD) is an increasingly prevalent and progressively disabling
      neurodegenerative disease. The impact of PD on patients and their families as
      well as its burden on health care systems could be substantially reduced by
      disease-modifying therapies that slow the rate of neurodegeneration or stop the
      disease process. Multiple agents have been studied in clinical trials designed to
      assess disease modification in PD, but all have failed. Over the last 3 years,
      clinical trials investigating the potential of adeno-associated virus serotype 2
      (AAV)-neuturin, coenzyme Q10, creatine, pramipexole, and pioglitazone reported
      negative findings or futility. Despite these disappointments, progress has been
      made by expanding our understanding of molecular pathways involved in PD to
      reveal new targets, and by developing novel animal models of PD for preclinical
      studies. Currently, at least eight ongoing clinical trials are testing the
      promise of isradipine, caffeine, nicotine, glutathione, AAV2-glial cell-line
      derived neurotrophic factor (GDNF), as well as active and passive immunization
      against alpha-synuclein (alpha-Syn). In this review, we summarize the clinical
      trials of disease-modifying therapies for PD that were published since 2013 as
      well as clinical trials currently in progress. We also discuss promising
      approaches and ongoing challenges in this area of PD research.

PMID- 26208211
TI  - Whole-exome sequencing as a diagnostic tool for distal renal tubular acidosis.
AB  - OBJECTIVE: Distal renal tubular acidosis (dRTA) is characterized by metabolic
      acidosis due to impaired renal acid excretion. The aim of this study was to
      demonstrate the genetic diagnosis of four children with dRTA through use of whole
      exome sequencing. METHODS: Two unrelated families were selected; a total of four
      children with dRTA and their parents, in order to perform whole-exome sequencing.
      Hearing was preserved in both children from the first family, but not in the
      second, wherein a twin pair had severe deafness. Whole-exome sequencing was
      performed in two pooled samples and findings were confirmed with Sanger
      sequencing method. RESULTS: Two mutations were identified in the ATP6V0A4 and
      ATP6V1B1 genes. In the first family, a novel mutation in the exon 13 of the
      ATP6V0A4 gene with a single nucleotide change GAC -> TAC (c.1232G>T) was found,
      which caused a substitution of aspartic acid to tyrosine in position 411. In the
      second family, a homozygous recurrent mutation with one base-pair insertion
      (c.1149_1155insC) in exon 12 of the ATP6V1B1 gene was detected. CONCLUSION: These
      results confirm the value of whole-exome sequencing for the study of rare and
      complex genetic nephropathies, allowing the identification of novel and recurrent
      mutations. Furthermore, for the first time the application of this molecular
      method in renal tubular diseases has been clearly demonstrated.

PMID- 26208212
TI  - Co-Infection Burden of Hepatitis C Virus and Human Immunodeficiency Virus among
      Injecting Heroin Users at the Kenyan Coast.
AB  - BACKGROUND: Injection drug use is steadily rising in Kenya. We assessed the
      prevalence of both human immunodeficiency virus type 1 (HIV-1) and hepatitis C
      virus (HCV) infections among injecting heroin users (IHUs) at the Kenyan Coast.
      METHODS: A total of 186 IHUs (mean age, 33 years) from the Omari rehabilitation
      center program in Malindi were consented and screened for HIV-1 and HCV by
      serology and PCR and their CD4 T-cells enumerated by FACS. RESULTS: Prevalence of
      HIV-1 was 87.5%, that of HCV was 16.4%, co-infection was 17.9% and 18/152 (11.8%)
      were uninfected. Only 5.26% of the HIV-1 negative injectors were HCV positive. Co
      infection was higher among injectors aged 30 to 40 years (20.7%) and among males
      (22.1%) than comparable groups. About 35% of the injectors were receiving
      antiretroviral treatment (ART). Co-infection was highest among injectors
      receiving D4T (75%) compared to those receiving AZT (21.6%) or TDF (10.5%) or
      those not on ART (10.5%). Mean CD4 T-cells were 404 (95% CI, 365 - 443) cells/mm3
      overall, significantly lower for co-infected (mean, 146; 95% CI 114 - 179
      cells/mm3) than HIV mono infected (mean, 437, 95% CI 386 - 487 cells/mm3,
      p<0.001) or uninfected (mean, 618, 95% CI 549 - 687 cells/mm3, p<0.001) injectors
      and lower for HIV mono-infected than uninfected injectors (p=0.002). By treatment
      arm, CD4 T-cells were lower for injectors receiving D4T (mean, 78; 95% CI, 0.4 -
      156 cells/mm3) than TDF (mean 607, 95% CI, 196 - 1018 cells/mm3, p=0.005) or AZT
      (mean 474, 95% CI -377 - 571 cells/mm3, p=0.004). CONCLUSION: Mono and dual
      infections with HIV-1 and HCV is high among IHUs in Malindi, but ART coverage is
      low. The co-infected IHUs have elevated risk of immunodeficiency due to
      significantly depressed CD4 T-cell numbers. Coinfection screening, treatment-as
      prevention for both HIV and HCV and harm reduction should be scaled up to
      alleviate infection burden.

PMID- 26208213
TI  - Quantitative Trait Loci Associated with the Tocochromanol (Vitamin E) Pathway in
      Barley.
AB  - The Genome-Wide Association Studies approach was used to detect Quantitative
      Trait Loci associated with tocochromanol concentrations using a panel of 1,466
      barley accessions. All major tocochromanol types- alpha-, beta-, delta-, gamma
      tocopherol and tocotrienol- were assayed. We found 13 single nucleotide
      polymorphisms associated with the concentration of one or more of these
      tocochromanol forms in barley, seven of which were within 2 cM of sequences
      homologous to cloned genes associated with tocochromanol production in barley
      and/or other plants. These associations confirmed a prior report based on bi
      parental QTL mapping. This knowledge will aid future efforts to better understand
      the role of tocochromanols in barley, with specific reference to abiotic stress
      resistance. It will also be useful in developing barley varieties with higher
      tocochromanol concentrations, although at current recommended daily consumption
      amounts, barley would not be an effective sole source of vitamin E. However, it
      could be an important contributor in the context of whole grains in a balanced
      diet. 

PMID- 26208214
TI  - The gray matter alterations in major depressive disorder and panic disorder:
      Putative differences in the pathogenesis.
AB  - OBJECTIVE: This is a comprehensive study to establish a diagnosis-specific gray
      matter deficit model for major depressive disorder (MDD) and panic disorder (PD).
      METHOD: We enrolled 53 patients with first-episode medication-naive PD, 54
      healthy controls and 53 patients with first-episode medication-naive MDD in this
      study. They were age, handedness and gender matched. All participating subjects
      all received baseline structural scanning by the 3-Tesla magnetic resonance
      scanner. The optimized voxel-based morphometry was performed on the 3 groups of
      subjects and the ANOVA analysis was used to estimate the inter-group gray matter
      differences between each group. RESULTS: The PD group had higher gray matter
      volume than MDD group in the right medial frontal cortex and right temporal
      gyrus. The PD group had gray matter reductions in the right inferior frontal
      gyrus and right insula. The MDD group had gray matter reductions in bilateral
      medial frontal cortex, right superior frontal gyrus, right superior temporal
      gyrus and bilateral cerebellums. CONCLUSION: The gray matter alterations of
      fronto-insula and fronto-temporo-cerebellum regions probably would be specific
      for PD and MDD respectively. In addition, the differences of gray matter volume
      in the fronto-temporal regions would be helpful to differentiate MDD from PD.

PMID- 26208215
TI  - Immediate Genetic and Epigenetic Changes in F1 Hybrids Parented by Species with
      Divergent Genomes in the Rice Genus (Oryza).
AB  - BACKGROUND: Inter-specific hybridization occurs frequently in higher plants, and
      represents a driving force of evolution and speciation. Inter-specific
      hybridization often induces genetic and epigenetic instabilities in the resultant
      homoploid hybrids or allopolyploids, a phenomenon known as genome shock. Although
      genetic and epigenetic consequences of hybridizations between rice subspecies
      (e.g., japonica and indica) and closely related species sharing the same AA
      genome have been extensively investigated, those of inter-specific hybridizations
      between more remote species with different genomes in the rice genus, Oryza,
      remain largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the
      immediate chromosomal and molecular genetic/epigenetic instability of three
      triploid F1 hybrids produced by inter-specific crossing between species with
      divergent genomes of Oryza by genomic in situ hybridization (GISH) and molecular
      marker analysis. Transcriptional and transpositional activity of several
      transposable elements (TEs) and methylation stability of their flanking regions
      were also assessed. We made the following principle findings: (i) all three
      triploid hybrids are stable in both chromosome number and gross structure; (ii)
      stochastic changes in both DNA sequence and methylation occurred in individual
      plants of all three triploid hybrids, but in general methylation changes occurred
      at lower frequencies than genetic changes; (iii) alteration in DNA methylation
      occurred to a greater extent in genomic loci flanking potentially active TEs than
      in randomly sampled loci; (iv) transcriptional activation of several TEs commonly
      occurred in all three hybrids but transpositional events were detected in a
      genetic context-dependent manner. CONCLUSIONS/SIGNIFICANCE: Artificially
      constructed inter-specific hybrids of remotely related species with divergent
      genomes in genus Oryza are chromosomally stable but show immediate and highly
      stochastic genetic and epigenetic instabilities at the molecular level. These
      novel hybrids might provide a rich resource of genetic and epigenetic diversities
      for potential utilization in rice genetic improvements.

PMID- 26208216
TI  - Investigation of a Measles Outbreak in China to Identify Gaps in Vaccination
      Coverage, Routes of Transmission, and Interventions.
AB  - BACKGROUND: A measles outbreak occurred in a western county of China in 2013, the
      year after China's historic nadir of measles. We conducted a field investigation
      to identify gaps in measles vaccination coverage and immunization program
      weaknesses, and to provide recommendations for measles outbreak response and
      immunization program improvement. METHODS: We analyzed surveillance data from
      2008 to 2013 to describe the measles epidemiology of the county. Measles
      containing vaccine coverage was estimated using two methods: previously-reported
      administrative coverage and an estimation of coverage by clinic-kept vaccination
      records (n = 542). We conducted a rapid field coverage assessment in a migrant
      population village to evaluate coverage after emergency vaccination. We conducted
      a review of hospital records of measles cases to address the role hospital
      transmission played during the early stage of this outbreak. RESULTS: There were
      153 cases in the outbreak, primarily among children too young to vaccinate,
      unvaccinated children less than 3 years old, and adults. Measles-containing
      vaccine coverage by the field assessment showed that 20% of children aged 8-17
      months had zero doses, and 9% of >=2 years old children had fewer than two doses.
      The vaccination statuses of all adult cases were either zero doses or unknown. At
      least 61% of cases had been hospitalized. The proportion of cases who had been
      hospital-exposed 7 to 21 days prior to rash onset decreased from 52% to 22% after
      hospitals strengthen their isolation measures. CONCLUSIONS: This outbreak was a
      result of measles vaccination coverage gaps among young children and adults, and
      insufficient hospital isolation of cases. The lower coverage seen in the field
      estimation compared with reported coverage showed that reported coverage could
      have been overestimated. Hospitals were sites of transmission in the early stage
      of the outbreak. A strict hospital isolation policy could decrease spread of
      measles. Emergency vaccination was associated with stopping measles transmission
      in low coverage areas.

PMID- 26208218
TI  - Risk Factors Associated with Stenotrophomonas maltophilia Bacteremia: A Matched
      Case-Control Study.
AB  - Stenotrophomonas maltophilia is an important nosocomial bacterial pathogen, as is
      Pseudomonas aeruginosa. Differentiation of these bacteria as bacteremic agents is
      critical in the clinical setting and to define a therapeutic strategy; however,
      the associated factors and prognosis for S. maltophilia bacteremia have not been
      fully evaluated to adequately characterize these factors. We first conducted a
      matched case-control study to clarify these questions. A total of 30 case
      patients with S. maltophilia bacteremia were compared with 30 control patients
      with P. aeruginosa bacteremia between January 2005 and August 2014, according to
      matching criteria based on underlying disease, age, and gender. The 30-day
      mortality rate for the case patients (53.3%) was significantly higher than that
      of the control group (30.0%) (P = 0.047, using the log-rank test). Conditional
      logistic regression analysis showed that the predisposing factors specific for
      the detection of S. maltophilia bacteremia were indwelling artificial products
      other than a central venous catheter, ICU stay, and previous use of anti-MRSA
      drugs. The high severity of illness was associated with mortality in both case
      and control patients. Interestingly, inappropriate antimicrobial treatment was an
      additional independent risk factor for mortality in only the case patients with
      S. maltophilia bacteremia (odds ratio = 13.64, P = 0.048). Monotherapy with
      fluoroquinolones inactive against the S. maltophilia isolates was mainly
      responsible for the inappropriate treatment. These results suggest that more
      precise prediction and more appropriate treatment might improve the prognosis of
      patients with S. maltophilia bacteremia. 

PMID- 26208217
TI  - Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring
      Neurodevelopment at 6 and 18 Months of Age--A Follow Up from the PREOBE Cohort.
AB  - BACKGROUND: Brain development in fetal life and early infancy is critical to
      determine lifelong performance in various neuropsychological domains. Metabolic
      pathologies such as overweight, obesity, and gestational diabetes in pregnant
      women are prevalent and increasing risk factors that may adversely affect long
      term brain development in their offspring. OBJECTIVE: The objective of this
      research was to investigate the influence of maternal metabolic pathologies on
      the neurodevelopment of the offspring at 6 and 18 months of life. DESIGN: This
      was a prospective case-control study of 331 mother- and child pairs from Granada,
      Spain. The mothers were included during pregnancy into four groups according to
      their pre-gestational body mass index and their gestational diabetes status;
      overweight (n:56), obese (n:64), gestational diabetic (n:79), and healthy normal
      weight controls (n:132). At 6 months and 18 months we assessed the children with
      the Bayley III scales of neurodevelopment. RESULTS: At 6 months (n=215), we found
      significant group differences in cognition composite language, and expressive
      language. Post hoc test revealed unexpectedly higher scores in the obese group
      compared to the normal weight group and a similar trend in overweight and
      diabetic group. The effects on language remained significant after adjusting for
      confounders with an adjusted odds ratio for a value above median in composite
      language score of 3.3 (95% CI: 1.1, 10.0; p=0.035) for children of obese mothers.
      At 18 month (n=197), the offspring born to obese mothers had lost five points in
      language composite scores and the previous differences in language and cognition
      was replaced by a suggestive trend of lower gross motor scores in the overweight,
      obese, and diabetic groups. CONCLUSIONS: Infants of obese mothers had a temporary
      accelerated development of cognition and language, followed by a rapid
      deceleration until 18 months of age, particularly of language scores. This novel
      observation prompts further confirmative studies to explore possible placental
      and neurodevelopmental mechanisms involved.

PMID- 26208219
TI  - Harnessing Nanoscale Confinement to Design Sterically Stable Vesicles of Specific
      Shapes via Self-Assembly.
AB  - We design sterically stable biocompatible vehicles with tunable shapes through
      the self-assembly of a binary mixture composed of amphiphilic molecular species,
      such as PEGylated lipids, and phospholipids under volumetric confinement. We use
      a molecular dynamics-based mesoscopic simulation technique called dissipative
      particle dynamics to resolve the aggregation dynamics, structure, and morphology
      of the hybrid aggregate. We examine the effect of confinement on the growth
      dynamics and shape of the hybrid aggregate, and demonstrate the formation of
      different morphologies, such as oblate and prolate shaped vesicles and bicelles.
      We perform these investigations by varying the degree of nanoscale confinement,
      for different relative concentrations of the species and the length of the
      functional groups. Results from our investigations can be used for the design and
      prediction of novel hybrid soft materials for applications requiring the
      encapsulation of therapeutic agents in micro- or nanofluidic channels. 

PMID- 26208220
TI  - Long-Term Trends in Esophageal Candidiasis Prevalence and Associated Risk Factors
      with or without HIV Infection: Lessons from an Endoscopic Study of 80,219
      Patients.
AB  - BACKGROUND: The prevalence of candida esophagitis (CE) might be changing in an
      era of highly active antiretroviral therapy (HAART) among HIV-infected patients
      or today's rapidly aging society among non-HIV-infected patients. However, few
      studies have investigated long-term CE trends, and CE risk factors have not been
      studied in a large sample, case-control study. This study aimed to determine long
      term trends in CE prevalence and associated risk factors for patients with or
      without HIV infection. METHODS: Trends in CE prevalence were explored in a cohort
      of 80,219 patients who underwent endoscopy between 2002 and 2014. Risks for CE
      were examined among a subcohort of 6,011 patients. In risk analysis, we assessed
      lifestyles, infections, co-morbidities, immunosuppressants, and proton-pump
      inhibitors (PPIs). All patients were tested for HIV, hepatitis B or C virus, and
      syphilis infection. For HIV-infected patients, sexual behavior, CD4 cell count,
      history of HAART were also assessed. RESULTS: CE prevalence was 1.7%
      (1,375/80,219) in all patients, 9.8% (156/1,595) in HIV-infected patients, and
      1.6% (1,219/78,624) in non-HIV-infected patients. CE prevalence from 2002-2003 to
      2012-2014 tended to increase in non-HIV-infected patients (0.6% to 2.5%; P<0.01)
      and decrease in HIV-infected patients (13.6% to 9.0%; P=0.097). Multivariate
      analysis revealed increasing age (odds ratio [OR], 1.02; p=0.007), HIV infection
      (OR, 4.92; p<0.001), and corticosteroid use (OR, 5.90; p<0.001) were
      significantly associated with CE, and smoking (OR, 1.32; p=0.085) and
      acetaminophen use (OR, 1.70; p=0.097) were marginally associated. No significant
      association was found with alcohol consumption, hepatitis B or C virus, syphilis,
      diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic
      kidney disease, liver cirrhosis, anticancer, or PPIs use. In HIV-infected
      patients, CD4 cell count <100/MUL (OR, 4.83; p<0.001) and prior HAART (OR, 0.35;
      p=0.006) were independently associated with CE, but sexual behavior was not.
      Among corticosteroid users, CE was significantly associated with higher
      prednisone-equivalent dose (p=0.043 for trend test). CONCLUSIONS: This large,
      endoscopy-based study demonstrated that CE prevalence increased in non-HIV
      infected patients but decreased in HIV-infected patients over 13 years. Risk
      analysis revealed that increasing age, HIV infection, and corticosteroids use,
      particularly at higher doses, were independently associated with CE, but alcohol,
      other infections, diabetes, anticancer drugs, and PPIs use were not.

PMID- 26208221
TI  - Vertical TiO2 Nanorods as a Medium for Stable and High-Efficiency Perovskite
      Solar Modules.
AB  - Perovskite solar cells employing CH3NH3PbI3-xClx active layers show power
      conversion efficiency (PCE) as high as 20% in single cells and 13% in large area
      modules. However, their operational stability has often been limited due to
      degradation of the CH3NH3PbI3-xClx active layer. Here, we report a perovskite
      solar module (PSM, best and av. PCE 10.5 and 8.1%), employing solution-grown TiO2
      nanorods (NRs) as the electron transport layer, which showed an increase in
      performance (~5%) even after shelf-life investigation for 2500 h. A crucial issue
      on the module fabrication was the patterning of the TiO2 NRs, which was solved by
      interfacial engineering during the growth process and using an optimized laser
      pulse for patterning. A shelf-life comparison with PSMs built on TiO2
      nanoparticles (NPs, best and av. PCE 7.9 and 5.5%) of similar thickness and on a
      compact TiO2 layer (CL, best and av. PCE 5.8 and 4.9%) shows, in contrast to that
      observed for NR PSMs, that PCE in NPs and CL PSMs dropped by ~50 and ~90%,
      respectively. This is due to the fact that the CH3NH3PbI3-xClx active layer shows
      superior phase stability when incorporated in devices with TiO2 NR scaffolds. 

PMID- 26208223
TI  - Palladium-catalyzed arylation of (di)azinyl aldoxime ethers by aryl iodides:
      stereoselective synthesis of unsymmetrical (E)-(di)azinylaryl ketoxime ethers.
AB  - The first example of direct arylation of (di)azinyl aldoxime ethers by aryl
      iodides is reported. The reaction produces, in a single step, a variety of
      geometrically pure unsymmetrical (E)-(di)azinylaryl ketoxime ethers, a class of
      nitrogenated motifs that have found wide applications in medicinal and organic
      chemistry but are difficult to access using conventional procedure. The utility
      of the method is further illustrated in a formal synthesis of the Merck melanin
      concentrating hormone 1 receptor antagonist. 

PMID- 26208224
TI  - Interest of Laparoscopy for "En Bloc" Resection of Primary Malignant Sacral
      Tumors by Combined Approach: Comparative Study With Open Median Laparotomy.
AB  - STUDY DESIGN: Retrospective case-control study. OBJECTIVE: To compare laparoscopy
      with open median laparotomy for anterior approach in "en bloc" resection of
      primary malignant sacral tumors (PMST) in combined approach strategy. SUMMARY OF
      BACKGROUND DATA: Wide margin surgical resection is the "gold standard" treatment
      of PMST. METHODS: Two groups of patients suffering from PMST and operated for "en
      bloc" resection by combined approach (anterior and posterior) only differencing
      for the anterior approach were constituted: "laparoscopy" group (n = 11) and
      "laparotomy" group (n = 22). Intraoperative morbidity (blood loss, red blood cell
      transfusion (RBC transfusion), surgical procedure duration) and postoperative
      morbidity (surgical-site infection (SSI), perineal dysfunctions, local
      recurrence) were analyzed. Surgical margins were studied. Data of both groups
      were compared using nonparametric Mann-Whitney test for continuous data and
      Fisher test for categorical data. Overall survival (OS) and Disease-free survival
      (DFS) were analyzed by Kaplan-Meier method. RESULTS: Blood loss during anterior
      approach was less important in "laparoscopy" group 71.9 mL (range 0-400 mL) as
      compared with 2140 mL (range 0-9000 mL) for "laparotomy" group (P = 0.019). Blood
      loss during posterior approach was not different between the 2 groups. Total
      blood loss including anterior and posterior approach was inferior in
      "laparoscopy" group 2208 mL (range 230-4800 mL) versus 5385.7 mL (range 1400
      11500 mL) for "laparotomy" group (P = 0.026). We reported significant difference
      on blood transfusion (3.7 RBC transfusions (range 0-8) for "laparoscopy group"
      versus 10.1 RBC transfusions (range 0-35) for "laparotomy" group (P = 0.025)).
      Surgical duration, quality of surgical margins, perineal dysfunctions and SSI
      were equivalent for both groups. At a follow-up of 36.6 months for "laparoscopy"
      group and 115.3 months for "laparotomy" group, OS and DFS were equivalent.
      CONCLUSION: Use of laparoscopy for anterior approach decreases intraoperative
      blood loss and intraoperative RBC transfusion without increasing surgical
      duration, without altering the quality of surgical margins and without impairing
      long-term outcomes. LEVEL OF EVIDENCE: 4.

PMID- 26208222
TI  - c-Myb Binding Sites in Haematopoietic Chromatin Landscapes.
AB  - Strict control of tissue-specific gene expression plays a pivotal role during
      lineage commitment. The transcription factor c-Myb has an essential role in adult
      haematopoiesis and functions as an oncogene when rearranged in human cancers.
      Here we have exploited digital genomic footprinting analysis to obtain a global
      picture of c-Myb occupancy in the genome of six different haematopoietic cell
      types. We have biologically validated several c-Myb footprints using c-Myb
      knockdown data, reporter assays and DamID analysis. We show that our predicted
      conserved c-Myb footprints are highly dependent on the haematopoietic cell type,
      but that there is a group of gene targets common to all cell-types analysed.
      Furthermore, we find that c-Myb footprints co-localise with active histone mark
      H3K4me3 and are significantly enriched at exons. We analysed co-localisation of c
      Myb footprints with 104 chromatin regulatory factors in K562 cells, and
      identified nine proteins that are enriched together with c-Myb footprints on
      genes positively regulated by c-Myb and one protein enriched on negatively
      regulated genes. Our data suggest that c-Myb is a transcription factor with
      multifaceted target regulation depending on cell type. 

PMID- 26208225
TI  - Usefulness of 3-dimensional Measurement of Ossification of the Posterior
      Longitudinal Ligament (OPLL) in Patients With OPLL-induced Myelopathy.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate the usefulness of 3
      dimensional (3D) measurement of ossification of the posterior longitudinal
      ligament (OPLL), and identify the reliability of a novel 3D method of
      measurement. SUMMARY OF BACKGROUND DATA: OPLL is not a 2-dimensional (2D)
      disease, but rather a 3D disease. Therefore, conventional measurement of
      parameters using radiography may not be suitable for evaluating OPLL. However,
      there is no study that investigated the correlation between 3D parameters of OPLL
      and clinical outcomes. METHODS: 50 patients (40 males and 10 females; mean age
      57.2 yr) with symptomatic OPLL were enrolled. Neurological and clinical outcome
      scales were measured using the Japanese Orthopedic Association (JOA) score,
      visual analogue scale, short-form health survey (SF-36) and neck disability
      index. A 3D model was reconstructed with digital imaging and communications in
      medicine files from axial computed tomographic images using software (MIMICS;
      Materialise, Leuven, Belgium) to obtain the following parameters: 3D volume of
      OPLL, 3D volume of the spinal canal (confined to the vertebral level involving
      OPLL), spinal canal diameter, thickness of OPLL, and length of OPLL. All patients
      were divided into 2 different groups, the mild myelopathy group (JOA score >=18,
      n = 11) and the severe myelopathy group (JOA score <=17, n = 23). RESULTS: The 3D
      OPLL volume did not correlate with clinical outcomes (r =-0.275, P = 0.116). 3D
      OPLL ratio and OPLL thickness had a significant negative relationship with JOA
      score (r =-0.502, P < 0.005 and r =-0.437, P < 0.05, respectively). In
      particular, 3D OPLL ratio was an independent risk factor for increased severity
      of myelopathy (B =-29.71, P < 0.05). The mild myelopathy group showed lower 3D
      OPLL ratio than the severe myelopathy group (0.092 vs. 0.148, P < 0.05).
      CONCLUSION: 3D method of measurement is superior to the conventional method in
      terms of evaluating the clinical state of symptomatic patients with OPLL. Higher
      3D OPLL ratio has an adverse effect on the spinal cord. LEVEL OF EVIDENCE: 3.

PMID- 26208226
TI  - Obstructive Hydrocephalus Due to Intraventricular Hemorrhage After Incidental
      Durotomy During Lumbar Spine Surgery.
AB  - STUDY DESIGN: Case report and review of literature. OBJECTIVE: To present an
      exceedingly rare occurrence of obstructive hydrocephalus secondary to
      intraventricular hemorrhage after incidental durotomy during lumbar spine
      surgery. SUMMARY OF BACKGROUND DATA: Incidental durotomies are uncommon but well
      recognized complications associated with spine surgery. Whereas mostly considered
      benign with no untoward clinical sequele, it can be symptomatic and present with
      spinal headaches, pseudomeningoceles, wound infection, meningitis and rarely
      intracerebral hemorrhage. METHODS: A 76-year-old woman underwent L3-S1
      laminectomies and fusion for lumbar spondylosis and stenosis. Intraoperatively, a
      small incidental durotomy was encountered and primarily repaired. RESULTS: The
      patient developed altered mental status on postoperative day 2. Computed
      tomography of the brain revealed obstructive hydrocephalus and intraventricular
      hemorrhage. The patient was immediately transferred to the neurosurgery intensive
      care unit and an external ventricular drain was placed emergently with high
      opening pressure. Her mental status improved immediately after cerebral spinal
      fluid diversion. The external ventricular drain was successfully removed after 8
      days. The patient made a full recovery and was discharged in stable condition.
      CONCLUSION: Obstructive hydrocephalus after intraventricular hemorrhage is an
      exceptionally rare but potentially life-threatening complication of incidental
      durotomies. Spine surgeons should be aware of this rare but serious complication.
      LEVEL OF EVIDENCE: 4.

PMID- 26208227
TI  - In Vivo Magnetic Resonance Imaging Evaluation of Porous Tantalum Interbody Fusion
      Devices in a Porcine Spinal Arthrodesis Model.
AB  - STUDY DESIGN: Animal experimental study. OBJECTIVE: To investigate the use of
      magnetic resonance (MR) imaging in the assessment of lumbar interbody fusion
      using porous tantalum implants in a porcine spinal fusion model. SUMMARY OF
      BACKGROUND DATA: Porous tantalum has been used successfully as a spinal interbody
      fusion device. However, to our knowledge, there has been no consensus on the
      optimal technique for evaluating spinal fusion when using porous tantalum
      implants. METHODS: Twelve 12-week-old female Danish Landrace pigs underwent 3
      levels of anterior lumbar interbody fusion at L2-3, L4-5 and L6-7. One level was
      fused using a solid porous tantalum cage with pedicle screw fixation. The other 2
      levels were fused using a hollow porous tantalum ring packed with autograft and
      stabilized anteriorly with staples. Six months postoperatively, T1-weighted, T2
      weighted, and gadolinium-DTPA contrast-enhanced MRI were obtained on a GE 1.5-T
      unit. After sacrifice, conventional radiograph and histological examination were
      carried out. RESULTS: Eleven pigs went through the experiment without
      complications. On all the MR sequences, there were significant higher signal
      intensity bands at the vertebrae-implant interface of nonfused segments compared
      with that of fused segments and the vertebral bone and implants themselves (P <
      0.001). There was an agreement between histological findings of fibrous tissues
      surrounding the implants and the high signal intensity band on T1- and T2
      weighted MR images respectively (sensitivity 69.6% and 56.5%, specificity 90.7%
      and 95.3%), both of which were superior to conventional radiograph images
      (sensitivity 52.2%, specificity 97.7%), especially the T1-weighted MR images.
      CONCLUSION: MR imaging could be an effective and noninvasive way to determine the
      fusion status of tantalum metal implants. Compared with T2-weighted MR imaging
      and conventional radiograph, T1-weighted spin-echo MR imaging is more sensitive
      and specific in detecting nonunion via the lucency between the vertebral body and
      tantalum metal device. LEVEL OF EVIDENCE: N/A.

PMID- 26208228
TI  - Subsequent Vertebral Fractures Post Cement Augmentation of the Thoracolumbar
      Spine: Does it Correlate With Level-specific Bone Mineral Density Scores?
AB  - STUDY DESIGN: A case-control study. OBJECTIVE: In this study, we investigated the
      correlation between level-specific preoperative bone mineral density and
      subsequent vertebral fractures. We also identified factors associated with
      subsequent vertebral fractures. SUMMARY OF BACKGROUND DATA: Complications of
      cement augmentation of the spine include subsequent vertebral fractures, leading
      to unnecessary morbidity and more treatment. Ability to predict at-risk vertebra
      will help guide management. METHODS: We studied all patients with osteoporotic
      compression fractures who underwent cement augmentation in a single institution
      from November 2001 to December 2010 by a single surgeon. Association between
      level-specific bone mineral density T-scores and subsequent fractures was
      assessed. Multivariable analysis was performed to identify significant factors
      associated with subsequent vertebral fractures. RESULTS: 93 patients followed up
      for a mean duration of 25.1 months (12-96) had a mean age of 76.8 years (47-99).
      Vertebroplasty was performed in 58 patients (62.4%) on 68 levels and kyphoplasty
      in 35 patients (37.6%) on 44 levels. Refracture was seen in 16 patients (17.2%).
      The time to subsequent fracture post cement augmentation was 20.5 months (2-90).
      For refracture cases, 43.8% (7/16) fractured in the adjacent vertebrae.
      Subsequently fractured vertebra had a mean T-score of -2.860 (95% confidence
      interval -3.268 to -2.452) and nonfractured vertebra had a mean T-score of -2.180
      (95% confidence interval -2.373 to -1.986). A T-score of -2.2 or lower is
      predictive of refracture at that vertebra (P = 0.047). Odds ratio increases with
      decreasing T-scores from -2.2 or lower to -2.6 or lower. A T-score of -2.6 or
      lower gives no additional predictive advantage. After multivariable analysis, age
      (P = 0.049) and loss of preoperative anterior vertebral height (P = 0.017) are
      associated with refracture. CONCLUSION: Level-specific T-scores are predictive of
      subsequent fractures and the odds ratio increases with lower T-scores from -2.2
      or less to -2.6 or less. They have a low positive predictive value, but a high
      negative predictive value for subsequent fractures. Other significant
      associations with subsequent refractures include age and anterior vertebral
      height. LEVEL OF EVIDENCE: 4.

PMID- 26208229
TI  - The Influence of Age and Sex on Cervical Spinal Alignment Among Volunteers Aged
      Over 50.
AB  - STUDY DESIGN: Large cohort study of volunteers aged over 50. OBJECTIVE: To
      investigate influence of age and sex on cervical sagittal alignment among
      volunteers aged over 50. SUMMARY OF BACKGROUND DATA: Few large-scale studies have
      described normative values in cervical spine alignment regarding age and sex
      among volunteers aged over 50. METHODS: The study cohort included 656 volunteers
      aged 50 to 89 years. Pelvic tilt, sacral slope, pelvic incidence, lumbar
      lordosis, pelvic incidence-lumbar lordosis, thoracic kyphosis, T1 slope (T1S),
      cervical lordosis (CL), C7 sagittal vertical axis (C7 SVA), C2-C7 SVA, and T1S-CL
      were measured using whole spine and pelvic radiographs taken in the standing
      position. Health-related quality of life was assessed using the EuroQOL (EQ-5D)
      standardized instrument for measurement of health outcome and Oswestry Disability
      Index. RESULTS: There were 36 subjects aged 50 to 59 years, 174 aged 60 to 69
      years, 311 aged 70 to 79 years, and 135 aged 80 to 89 years. Average T1S for each
      decade was 32 degrees , 31 degrees , 33 degrees , and 36 degrees  for males, and
      28 degrees , 29 degrees , 32 degrees , and 37 degrees  for females, respectively.
      Average C2-C7 SVA was 25, 28, 34, and 35 mm for males, and 20, 21, 22, and 28 mm
      for females, respectively. C2-C7 SVA 40 mm or more, T1S 40 degrees  or more, and
      T1S-CL 20 degrees  or more pertaining to EQ-5D were significantly worse in other
      cases. CONCLUSION: C2-C7 SVA was significantly greater in males among all age
      groups, particularly among those with C2-C7 SVA of 40 mm or more [males, 69%
      (82/118) vs. females, 33% (36/118)]. Sagittal parameters of cervical spine were
      significantly worse in males than females. C2-C7 SVA, T1S, and T1S-CL negatively
      influenced EQ-5D. These results help to explain the greater prevalence of
      cervical spondylotic myelopathy among elderly males. LEVEL OF EVIDENCE: 3.

PMID- 26208230
TI  - Two Doses of Tranexamic Acid Reduce Blood Transfusion in Complex Spine Surgery: A
      Prospective Randomized Study.
AB  - STUDY DESIGN: Prospective, double-blinded, randomized controlled study.
      OBJECTIVE: To determine whether the use of 2 doses of tranexamic acid (TXA) can
      reduce perioperative blood loss and blood transfusions in low-risk adult patients
      undergoing complex laminectomy. SUMMARY OF BACKGROUND DATA: Complex laminectomy
      (multilevel laminectomy or laminectomy and instrumentation) is a procedure with a
      medium risk of blood loss, which may require allogeneic blood transfusion.
      Previous studies of TXA showed its inconsistent effectiveness in reducing blood
      loss during spine surgery. The negative results may stem from ineffective use of
      a single dose of TXA during long and complex operations. METHODS: 80 adult (18-65
      yr old) patients in Siriraj Hospital, Mahidol University, Thailand were enrolled
      and allocated into 2 groups (40 patients in each group) by computer-generated
      randomization. Patients with history of thromboembolic diseases were excluded.
      Anesthesiologists in charge and patients were blinded. Group I received 0.9% NaCl
      (NSS) or placebo and group II received 2 doses (15 mg/kg) of TXA. The first dose
      was administered before anesthesia induction and the second dose, after 3 hours.
      The assessed outcomes were the amount of perioperative blood loss and the
      incidence of blood transfusions. RESULTS: 78 patients were analyzed (1 patient in
      each group was excluded) with 39 patients randomized to each group. There were no
      differences in patient demographics and pre and postoperative hematocrit levels.
      The total blood loss in the control group (NSS) was higher [900 (160, 4150) mL]
      than in the TXA group [600 (200, 4750) mL]. Patients in the control group
      received more crystalloid, colloid, and packed red blood cell transfusions.
      Within 24 hours, we observed a 64.6% reduction of blood transfusions (43.5%
      vs.15.4%, P = 0.006). No serious thromboembolic complications occurred.
      CONCLUSION: 2 effective doses (15 mg/kg) of TXA can reduce blood loss and
      transfusions in low-risk adults undergoing complex spine surgery. LEVEL OF
      EVIDENCE: 1.

PMID- 26208231
TI  - L5 Radiculopathy due to Foraminal Stenosis Accompanied With Vacuum Phenomena of
      the L5/S Disc on Radiography Images in Extension Position.
AB  - STUDY DESIGN: Retrospective study for L5 radiculopathy due to foraminal stenosis
      with vacuum phenomena (VP) at the L5/S disc. OBJECTIVE: To investigate the
      influence of the L5/S VP on L5 radiculopathy, due to L5/S foraminal stenosis.
      SUMMARY OF BACKGROUND DATA: Foraminal stenosis has often been detected via
      images. However, although this condition is well known, it is occasionally
      overlooked during diagnosis, because spinal nerve compression is not always
      visible on stationary images. METHODS: Patients who underwent lumbar spine
      surgery were examined to determine the presence of foraminal stenosis (n = 194).
      The presence of VP and the range of motion of the L5/S disc were assessed on
      radiography with the lumbar spine in the extended and flexed positions. The
      shapes of the L5/S foramina were confirmed using sagittal magnetic resonance
      imaging. Patients who showed VP were divided into 2 groups: patients with (group
      A) and without (group B) symptomatic foraminal stenosis. The relationship between
      the VP and symptomatic foraminal stenosis was examined. RESULTS: In total, 35
      cases of VP at the L5/S disc were noted on lateral radiography. L5 radiculopathy
      due to L5/S foraminal stenosis was identified in 14 of these 35 cases. The ranges
      of L5/S angles were 10 degrees  +/- 4 degrees  and 5 degrees  +/- 3 degrees  in
      groups A and B, respectively, and these values were significantly different (P <
      0.01). 11 (48%) of 23 L5/S foramina that showed VP of the L5/S disc and were
      completely occupied by a disc below the caudal edge of the vertebra had
      symptomatic foraminal stenosis. CONCLUSION: Our results indicated that VP, which
      showed a large range of motion angle between flexion and extension, triggered
      symptoms of foraminal stenosis at the L5/S disc. The dynamic motion of the VP
      should thus be considered for the diagnosis of L5/S foraminal stenosis. LEVEL OF
      EVIDENCE: 3.

PMID- 26208232
TI  - 2015 Updated Method Guideline for Systematic Reviews in the Cochrane Back and
      Neck Group.
AB  - STUDY DESIGN: Method guideline for systematic reviews of trials of interventions
      for neck and back pain, and related spinal disorders. OBJECTIVE: To help authors
      design, conduct, and report systematic reviews of trials in this field. SUMMARY
      OF BACKGROUND DATA: In 1997, the Cochrane Back Review Group editorial board
      published the Method Guideline for Systematic Reviews, which was updated in 2003
      and in 2009. Since then, new methodological evidence has emerged and standards
      have changed, therefore it was clear that revisions were needed to the 2009
      guideline. In May 2015 the group changed its name to Cochrane Back and Neck.
      METHODS: The editorial board met in September 2014 to review the relevant new
      methodological evidence and determine how it should be incorporated. Members of
      the advisory board were consulted. Based on the feedback received, an updated
      method guideline was prepared and approved by the editorial board. RESULTS: We
      have updated recommendations in 7 categories: objectives, literature search,
      selection criteria, risk of bias assessment, data extraction, data analysis, and
      reporting of results and conclusions. Each category is classified into minimum
      criteria (mandatory) and further guidance (optional). This update also includes
      some new guidance for preparation of summary of finding tables and for conducting
      nonintervention reviews. CONCLUSION: Citations of previous versions of the method
      guideline in published scientific articles (1193 in total) suggest that others
      may find this guideline useful to plan, conduct, or evaluate systematic reviews
      in the field of back and neck pain, and spinal disorders. LEVEL OF EVIDENCE: N/A.

PMID- 26208233
TI  - Esophageal infections: an update.
AB  - PURPOSE OF REVIEW: Infectious esophagitis generally occurs in patients with
      impaired immunity. Although methods to suppress the immune system evolve, the
      potential infectious consequences are poorly understood. The purpose of this
      article is to review the risk factors, diagnosis, and treatment of infectious
      esophagitis. RECENT FINDINGS: Minimal pediatric data, including a few case
      reports and series, involve infectious esophagitis. Esophageal infections are
      usually caused by the following microbes, in order starting with the most common:
      Candida albicans, herpes simplex virus, and cytomegalovirus. Uncommon risk
      factors in these and other reports include epidural triamcinolone and oral
      budesonide in addition to more common risk factors such as HIV infection,
      chemotherapeutic agents, and transplant immunosuppressive medications. Rare
      reports involve immunocompetent patients and treatment of these patients is
      controversial. SUMMARY: Understanding of infectious esophagitis is growing, and
      risk factors, diagnosis, and treatments are evolving.

PMID- 26208234
TI  - Current concepts in functional gastrointestinal disorders.
AB  - PURPOSE OF REVIEW: Functional gastrointestinal disorders (FGIDs) are some of the
      most common and challenging disorders in pediatrics. Recurrent abdominal pain is
      the central feature of pain-associated FGIDs such as irritable bowel syndrome. A
      thorough understanding of current pathophysiological concepts is essential to
      successful management. RECENT FINDINGS: The brain-gut axis, role of microbiota
      and the biopsychosocial model are emerging concepts in FGIDs. The biopsychosocial
      model focuses on the interplay between genes, environment, and physical and
      psychosocial factors. Interactions between microbiota and the central, enteric
      and autonomic nervous systems form the link between gut functions and conscious
      perceptions. Irritable bowel syndrome is the most extensively studied and
      prototypical pain-associated FGIDs. An aberrant processing of pain or physiologic
      signals originating from the gut causes a state of visceral hypersensitivity - a
      central mechanism of functional pain. Psychosocial and autonomic influences also
      play large roles. Therapy is tailored to the individual patient and comorbid
      symptoms. SUMMARY: This review highlights the complex mechanisms and the aberrant
      brain-gut neural connections forming the basis of FGIDs. Successful management of
      FGIDs requires knowledge of the underlying pathophysiology coupled with a
      multidisciplinary treatment approach. Management should focus on cognitive
      behavioral therapy, dietary factors along with gastrointestinal motility and
      psychotropic drug therapy.

PMID- 26208235
TI  - Colonic polyps and polyposis syndromes in pediatric patients.
AB  - PURPOSE OF REVIEW: Gastrointestinal polyps are commonly encountered during
      childhood and are one of the most common causes of rectal bleeding in this age
      group. Most polyps are benign and located in the colon, with the most frequent
      type being juvenile polyps. However, in older pediatric patients, if multiple
      polyps are present, in patients who have a positive family history, or if polyps
      are located outside of the colon, either adenomatous polyps or polyps associated
      with genetic abnormalities are more common. RECENT FINDINGS: Imaging techniques
      such as ultrasound and computed tomographic colonoscopy have recently been
      utilized to identify simple juvenile colonic polyps in children with rectal
      bleeding in whom there is a high index of suspicion. Colonoscopy with polypectomy
      is still required for histologic evaluation and resection of the polyp. There
      have been significant advances in genetic testing and management of hereditary
      gastrointestinal cancer syndromes with onset in childhood or adolescence that may
      ultimately reduce long-term morbidity and mortality. In addition to enhanced
      gastrointestinal and extraintestinal malignancy screening for affected
      individuals, specific gene mutations within a given condition such as adenomatous
      polyposis coli may predict clinical course and timing of specific interventions
      such as colectomy. In other conditions such as phosphatase and tensin homolog
      hamartoma tumor syndrome, phenotype may not be predicted by genotype. SUMMARY:
      Pediatricians, pediatric gastroenterologists, and adult gastroenterologists
      caring for children should understand how to differentiate benign polyps in the
      pediatric age group from those associated with a higher risk of complications
      including recurrence risk and risk of development of intestinal or
      extraintestinal malignancy. Recent advances in genetic testing, as well as
      development of consensus guidelines, are key in the identification, screening,
      and follow-up of children and adolescents with polyposis syndromes.

PMID- 26208236
TI  - Quality improvement through collaboration: the National Pediatric Quality
      improvement Collaborative initiative.
AB  - PURPOSE OF REVIEW: The National Pediatric Quality Improvement Collaborative
      (NPCQIC) was established to improve outcomes and quality of life in children with
      hypoplastic left heart syndrome and other single ventricle lesions requiring a
      Norwood operation. The NPCQIC consists of a network of providers and families
      collecting longitudinal data, conducting research, and using quality improvement
      science to decrease variations in care, develop and spread best practices, and
      decrease mortality. RECENT FINDINGS: Initial descriptive investigation of the
      collaborative data found interstage care process variations, different surgical
      strategies, diverse feeding practices, and variable ICU approaches between
      centers and within sites. Analysis and evaluation of these practice variations
      have allowed centers to learn from each other and implement change to improve
      processes. There has been an improvement in performance measures and most
      importantly, a 39.7% reduction in mortality. SUMMARY: The NPCQIC has shown, in a
      rare disease such as hypoplastic left heart syndrome that a network based on
      multicenter collaboration, patient (parent) engagement, and quality improvement
      science can facilitate change in practices and improvement in outcomes.

PMID- 26208237
TI  - Drug-induced liver injury in children.
AB  - PURPOSE OF REVIEW: Drug-induced liver injury (DILI) is an underrecognized cause
      of pediatric liver disease, accounts for almost 20% of pediatric acute liver
      failure cases, and is a major reason for liver transplantation in the USA. This
      article reviews the pathogenesis of DILI, approach to diagnosis and management,
      and highlights recent pediatric DILI case series. RECENT FINDINGS: Select
      individuals have an increased propensity to develop DILI. Known genetic
      polymorphisms of enzymes and host factors play an important role in medication
      management and influence the clinical outcome in 20-25% of all drug therapies.
      Children are more likely to have mitochondrial dysfunction from drugs, increasing
      their susceptibility to severe liver injury or acute liver failure. Antibiotics
      and central nervous system agents account for the majority of pediatric DILI in
      the West, although herbals are becoming more common. SUMMARY: Clinical features
      of DILI vary and overlap so exclusion of other conditions, identification of
      latency period and risk factors, and use of a searchable database can aid
      evaluation. Treatment consists of cessation of the offending agent and supportive
      care. Areas needing further research include elucidating mechanisms, identifying
      at risk individuals, and therapeutic interventions.

PMID- 26208238
TI  - Ultrasensitive label-free immunoassay for optical determination of amitriptyline
      and related tricyclic antidepressants in human serum.
AB  - The present work focuses on the development of a label-free and ultrasensitive
      immunoassay for the detection of the drug amitriptyline in human serum.
      Reflectometric interference spectroscopy is used as the detection method,
      providing a simple, but highly sensitive optical setup. Amitriptyline is a common
      antidepressant; however, it has a small therapeutic window and can cause severe
      side effects in case of wrong dosage. Therefore, it is highly recommended for
      therapeutic drug monitoring to control the drug level. The limit of detection for
      this optical immunosensor was determined in buffer (0.3 MUg/L) and in human serum
      (0.5 MUg/L). It has become evident that this assay can compete with HPLC
      measurements. For drug concentrations at a normal level or above, the sample can
      be diluted up to 1:100. Especially for limited sample volumes, this is a great
      advantage. The sensor surface shows very high stability, and together with the
      regeneration solution 80 measurement cycles can be performed on each transducer
      chip. Cross-reactivity experiments indicate that a sum determination of several
      tricyclic antidepressants is possible. 

PMID- 26208239
TI  - Extradural implantation of sacral anterior root stimulator in spinal cord injury
      patients.
AB  - AIMS: To evaluate the efficacy and complications of extradural sacral anterior
      root stimulation (SARS) implantation in patients with neurogenic detrusor
      overactivity (NDO) resulting from spinal cord injury (SCI). MATERIALS AND
      METHODS: A retrospective study was conducted between 2009 and 2013, on
      consecutive patients with NDO associated with SCI that underwent SARS
      implantation. We evaluated those factors related to clinical symptoms such as
      urinary infection rate, erections, and episodes of autonomic dysreflexia. Data
      from cystometric bladder capacity (CBC) and post-void residual (PVR) volume were
      also analyzed. RESULTS: Of the 104 patients included in the study, 95 (91%)
      patients were men with a mean (standard deviation) (SD) age of 38 (10) years.
      Mean (SD) time between the onset of SCI and the SARS was 78.2 (59.0) months. At
      baseline, 95 (91%) patients had urinary infections as compared with 16 (15%)
      after treatment, P < 0.001. The percentage of patients that had urinary
      incontinence was significantly higher at baseline than that observed after SARS,
      100% versus 14%, respectively, P < 0.001. Similar results were obtained regarding
      dysreflexia, P < 0.001. After SARS, the mean (SD) bladder capacity was 362 (108)
      ml and 98 (94%) patients had a bladder capacity greater than 400 ml. As regard to
      the adverse effects, six patients (6%) required a suburethral mesh implant and
      two (2%) patients had an infection, 4 and 5 months after SARS, respectively.
      CONCLUSIONS: Extradural implantation of SARS seems to be an effective and safe
      procedure in patients with spinal cord injury and neurogenic detrusor
      overactivity. Neurourol. Urodynam. 35:970-974, 2016. (c) 2015 Wiley Periodicals,
      Inc.

PMID- 26208240
TI  - Editor-in-Chief Commentary.

PMID- 26208242
TI  - Reliably estimating ambulatory activity in youth with arthrogryposis.
AB  - PURPOSE: Quantification of the physical activity levels using pedometers and
      accelerometers in children and adolescents with mobility limitations has recently
      allowed researchers and practitioners to track real-life outcomes of new
      interventions in this particular population. Questions remain concerning the
      reliability of ambulatory activity monitoring in functionally challenged youth.
      The purpose of the analysis, therefore, was to document the minimal number of
      days required to reliably estimate ambulatory activity levels in children with
      arthrogryposis. METHODS: Thirteen boys and girls with arthrogryposis (average age
      10.9 years) completed stepping activity monitoring using a two-dimensional
      accelerometer over a period of up to 15 consecutive days. Generalizability theory
      was applied to identify sources of variance in daily step counts
      (generalizability study, G study) and to determine the number of days necessary
      to obtain a reliable coefficient of >=0.80 (decision study, D study). RESULTS: G
      study results showed that intra-individual variability was larger (58.4% of total
      variance) than inter-individual variability (28.7% of total variance). D study
      indicated that 9 days of monitoring was required to reach a stable measure of
      ambulatory activity. CONCLUSIONS: Due to relatively greater variability in step
      counts across days of the week, a longer monitoring period was required for youth
      with arthrogryposis. Implication for Rehabilitation Large proportion of variance
      in daily step counts was attributable to unidentifiable sources of variance,
      suggesting further exploration of factors that influence on the walking activity
      in youth with arthrogryposis. Step activity monitoring of youth with
      arthrogryposis should occur over a 9-day period to reliably capture their
      habitual level of ambulation. Rehabilitation programs aimed to promote increased
      stepping in youth with arthrogryposis which can utilize the findings of the
      present study to appropriately track their effectiveness.

PMID- 26208243
TI  - Optimizing social participation in community-dwelling older adults through the
      use of behavioral coping strategies.
AB  - PURPOSE: This study aimed to (1) determine the categories of behavioral coping
      strategies most strongly correlated with optimal seniors' social participation in
      different activity and role domains and (2) identify the demographic, health and
      environmental factors associated with the use of these coping strategies
      optimizing social participation. METHOD: The sample consisted of 350 randomly
      recruited community-dwelling older adults (>=65 years). Coping strategies and
      social participation were measured, respectively, using the Inventory of Coping
      Strategies Used by the Elderly and Assessment of Life Habits questionnaires.
      Information about demographic, health and environmental factors was also
      collected during the interview. RESULTS: Regression analyses showed a strong
      relationship between the use of cooking- and transportation-related coping
      strategies and optimal participation in the domains of nutrition and community
      life, respectively. Older age and living alone were associated with increased use
      of cooking-related strategies, while good self-rated health and not living in a
      seniors' residence were correlated with greater use of transportation-related
      strategies. CONCLUSIONS: Our study helped to identify useful behavioral coping
      strategies that should be incorporated in disability prevention programs designed
      to promote community-dwelling seniors' social participation. However, the
      appropriateness of these strategies depends on whether they are used in relevant
      contexts and tailored to specific needs. IMPLICATIONS FOR REHABILITATION: Our
      results support the relevance of including behavioral coping strategies related
      to cooking and transportation in disability prevention programs designed to
      promote community-dwelling seniors' social participation in the domains of
      nutrition and community life, respectively. Older age and living alone were
      associated with increased use of cooking-related strategies, while good self
      rated health and not living in a seniors' residence were correlated with greater
      use of transportation-related strategies. These factors should be considered in
      order to optimize implementation of these useful strategies in disability
      prevention programs. The appropriateness of these selected strategies depends on
      whether they are used in relevant contexts and tailored to specific needs.

PMID- 26208244
TI  - Optimising leisure participation: a pilot intervention study for adolescents with
      physical impairments.
AB  - PURPOSE: To assess the feasibility of an intervention to improve participation in
      leisure activities of adolescents with physical impairments by changing aspects
      of the activity or environment. METHODS: A pre-test/post-test pilot study of a
      multi-strategy intervention was used to explore the effectiveness of the
      strategies and to determine whether the intervention was practical to apply in a
      community setting. The intervention involved establishing adolescent and family
      focused goals, measuring and addressing environmental barriers and building
      activity performance skills. The Goal Attainment Scale (GAS) and the Canadian
      Occupational Performance Measure measured outcomes. RESULTS: Eight participants
      (aged 12-19 years; five males) with physical disabilities set participation goals
      using a structured approach. Analysis of personal and environmental barriers and
      facilitators for participation guided the choice of intervention strategies to
      support goal attainment. The natural environment, government policies and
      availability of transport were identified as the most frequent barriers to
      participation in leisure. Support to secure appropriate devices to enable
      participation was commonly required. As a group, attainment of 12 of 17 GAS
      goals, and progress on four more goals, was demonstrated. CONCLUSIONS: The
      intervention model was applicable and practical to use in a community therapy
      setting and the majority of the participation goals set were achieved.
      IMPLICATIONS FOR REHABILITATION: This ICF-based intervention model was applicable
      and practical to use in a community therapy setting. The majority of the
      adolescent's leisure participation goals were achieved following engagement in
      the multi-strategy intervention. Adolescents with sufficient communication skills
      (CFCS Levels I-III) benefited from a group-based intervention in addition to
      individualised support.

PMID- 26208245
TI  - Feasibility and results of a case study of yoga to improve physical functioning
      in people with chronic traumatic brain injury.
AB  - PURPOSE: The purpose of this mixed-methods case study was to investigate whether
      an 8-week 1:1 yoga program was feasible and beneficial to people with traumatic
      brain injury (TBI). METHOD: This was a mixed-methods case study of one-to-one
      yoga for people with TBI included three people. We completed assessments before
      and after the 8-week yoga intervention and included measures of balance, balance
      confidence, pain, range of motion, strength and mobility. Qualitative interviews
      were included at the post-assessment. We include a percent change calculation and
      salient quotes that represent the perceived impact of the yoga intervention.
      RESULTS: All participants completed the yoga intervention and all demonstrated
      improvements in physical outcome measures. For the group, balance increased by
      36%, balance confidence by 39%, lower extremity strength by 100% and endurance by
      105%. Qualitative data support the use of yoga to improve multiple aspects of
      physical functioning, one participant stated: "I mean it's rocked my world. It's
      changed my life. I mean all the different aspects. I mean physically,
      emotionally, mentally, it's given me you know my life back...". CONCLUSIONS:
      Yoga, delivered in a one-to-one setting, appears to be feasible and beneficial to
      people with chronic TBI. IMPLICATIONS FOR REHABILITATION: Chronic traumatic brain
      injury (TBI) leads to many aspects of physical functioning impairment. Yoga
      delivered in a one-to-one setting may be feasible and beneficial for people with
      chronic TBI.

PMID- 26208246
TI  - Use of targeted next-generation sequencing for molecular diagnosis of
      craniosynostosis: Identification of a novel de novo mutation of EFNB1.
AB  - Craniofrontonasal syndrome (CFNS; MIM#304110) is characterized by asymmetric
      facial features with hypertelorism and a broad bifid nose due to synostosis of
      the coronal suture. CFNS shows a unique X-linked inheritance pattern (most
      affected patients are female and obligate male carriers exhibit a mild
      manifestation or no typical features at all) associated with the ephrin-B1 gene
      (EFNB1) located in the Xq13.1 region. In this study, we performed targeted,
      massively parallel sequencing using a next-generation sequencer, and identified a
      novel EFNB1 mutation, c.270_271delCA, in a Japanese female patient with
      craniosynostosis. Because subsequent Sanger sequencing identified no mutation in
      either parent, this mutation was determined to be de novo in origin. After
      obtaining molecular diagnosis, a retrospective clinical evaluation confirmed the
      clinical diagnosis of CFNS in this patient. Comprehensive molecular diagnosis
      using a next-generation sequencer would be beneficial for early diagnosis of the
      patients with undiagnosed craniosynostosis. 

PMID- 26208247
TI  - Synthesis and Solvatochromism of Substituted 4-(Nitrostyryl)phenolate Dyes.
AB  - 4-(Nitrostyryl)phenols 2a-9a were synthesized, and by deprotonation in solution,
      the solvatochromic phenolates 2b-9b were formed. Their absorption bands in the
      vis region of the spectra are due to pi-pi* electronic transitions, of an
      intramolecular charge-transfer nature, from the electron-donor phenolate toward
      the electron-acceptor nitroarene moiety. The frontier molecular orbitals and
      natural bond orbitals were analyzed for the protonated and deprotonated forms.
      The calculated geometries are in agreement with X-ray structures observed for 4a,
      6a, and 8a. The HOMO-LUMO energy gaps suggest that, after their deprotonation, an
      increase in the electron delocalization is observed. In the protonated compounds,
      the HOMO is primarily localized over the phenol ring and the C?C bridge. After
      deprotonation, it extends toward the entire molecule, including the NO2 groups.
      The solvatochromism of each dye was studied in 28 organic solvents, and it was
      found that all compounds exhibit a reversal in solvatochromism, which is
      interpreted in terms of the ability of the media to stabilize their electronic
      ground and excited states to different extents. The Catalan multiparameter
      equation is used in the interpretation of the solvatochromic data, revealing that
      the most important contribution to the solute/solvent interaction is the hydrogen
      bond donor acidity of the solvent. 

PMID- 26208248
TI  - Rh(III)-Catalyzed [4 + 1] Annulations of 2-Hydroxy- and 2-Aminobenzaldehydes with
      Allenes: A Simple Method toward 3-Coumaranones and 3-Indolinones.
AB  - A novel method for the regio- and stereoselective synthesis of substituted 3
      coumaranones from salicylaldehydes and allenes using a rhodium(III) catalyst has
      been developed. This procedure gives access to new 2-vinyl-substituted 3
      coumaranone compounds. The method involves a Rh(III)-catalyzed aldehyde C-H
      activation and annulation reactions. Moreover, this Rh(III)-catalyzed [4 + 1]
      annulation reaction has been applied to 2-aminobenzaldehydes to afford 2,2
      disubstituted 3-indolinones. 

PMID- 26208249
TI  - Physico-chemical characteristics of Longissimus lumborum muscle in goats
      subjected to halal slaughter and anesthesia (halothane) pre-slaughter.
AB  - This study assessed the effect of halal slaughter and anesthesia pre-slaughter
      followed by bleeding on meat quality characteristics of goats. Eleven male Boer
      cross goats were divided into two groups and subjected to either halal slaughter
      (HS) or anesthesia with halothane and propofol pre-slaughter (AS). At pre-rigor,
      HS had significantly lower (P < 0.05) muscle pH and glycogen than AS. However, no
      significant difference was observed in the pH and glycogen content between the
      treatments on 1, 3 and 7 days post mortem. The drip loss of HS was significantly
      lower (P < 0.05) than that of AS at all aging periods. Treatment had no effect on
      sarcomere length, myofibrillar fragmentation index and shear force values, loss
      of thiol groups and degradation of major myofibrillar proteins. It can be
      concluded that HS did not have deleterious effect on meat quality traits of goat
      when compared to AS. 

PMID- 26208250
TI  - Evaluation of (95)Mo Nuclear Shielding and Chemical Shift of [Mo6X14](2-)
      Clusters in the Liquid Phase.
AB  - [Mo6X14](2-) octahedral molybdenum clusters are the main building blocks of a
      large range of materials. Although (95)Mo nuclear magnetic resonance was proposed
      to be a powerful tool to characterize their structural and dynamical properties
      in solution, these measurements have never been complemented by theoretical
      studies which can limit their interpretation for complex systems. In this
      Article, we use quantum chemical calculations to evaluate the (95)Mo chemical
      shift of three clusters: [Mo6Cl14](2-), [Mo6Br14](2-), and [Mo6I14](2-). In
      particular, we test various computational parameters influencing the quality of
      the results: size of the basis set, treatment of relativistic and solvent
      effects. Furthermore, to provide quantum chemical calculations that are directly
      comparable with experimental data, we evaluate for the first time the (95)Mo
      nuclear magnetic shielding of the experimental reference, namely, MoO4(2-) in
      aqueous solution. This is achieved by combining ab initio molecular dynamics
      simulations with a periodic approach to evaluate the (95)Mo nuclear shieldings.
      The results demonstrate that, despite the difficulty to obtain accurate (95)Mo
      chemical shifts, relative values for a cluster series can be fairly well
      reproduced by DFT calculations. We also show that performing an explicit solvent
      treatment for the reference compound improves by ~50 ppm the agreement between
      theory and experiment. Finally, the standard deviation of ~70 ppm that we
      calculate for the (95)Mo nuclear shielding of the reference provides an
      estimation of the accuracy we can achieve for the calculation of the (95)Mo
      chemical shifts using a static approach. These results demonstrate the growing
      ability of quantum chemical calculations to complement and interpret complex
      experimental measurements. 

PMID- 26208251
TI  - Nonlinear effects in infrared action spectroscopy of silicon and vanadium oxide
      clusters: experiment and kinetic modeling.
AB  - For structural assignment of gas phase compounds, infrared action spectra are
      usually compared to computed linear absorption spectra. However, action
      spectroscopy is highly nonlinear owing to the necessary transfer of the
      excitation energy and its subsequent redistribution leading to statistical
      ionization or dissociation. Here, we examine by joint experiment and dedicated
      modeling how such nonlinear effects affect the spectroscopic features in the case
      of selected inorganic clusters. Vibrational spectra of neutral silicon clusters
      are recorded by tunable IR-UV two-color ionization while IR spectra for cationic
      vanadium oxide clusters are obtained by IR multiphoton absorption followed by
      dissociation of the bare cluster or of its complex with Xe. Our kinetic modeling
      accounts for vibrational anharmonicities, for the laser interaction through
      photon absorption and stimulated emission rates, as well as for the relevant
      ionization or dissociation rates, all based on input parameters from quantum
      chemical calculations. Comparison of the measured and calculated spectra
      indicates an overall agreement as far as trends are concerned, except for the
      photodissociation of the V3O7(+)-Xe messenger complex, for which anharmonicities
      are too large and poorly captured by the perturbative anharmonic model. In all
      systems studied, nonlinear effects are essentially manifested by variations in
      the intensities as well as spectral broadenings. Differences in some band
      positions originate from inaccuracies of the quantum chemical data rather than
      specific nonlinear effects. The simulations further yield information on the
      average number of photons absorbed, which is otherwise unaccessible information:
      several to several tens of photons need to be absorbed to observe a band through
      dissociation, while three to five photons can be sufficient for detection of a
      band via IR-UV ionization. 

PMID- 26208252
TI  - Adolescent Drinking Risks Associated with Specific Drinking Contexts.
AB  - BACKGROUND: To identify drinking contexts toward which prevention efforts should
      be directed, associations of context-specific alcohol use (past-year frequency of
      drinking and heavier drinking in the context) with a range of alcohol-related
      problems were examined in a population sample of adolescents. METHODS: A sample
      of youths (ages 15 to 18) residing in 50 medium-to-large California cities (n =
      473 drinkers) was obtained. Respondents provided information about 7 past-year
      alcohol-related problems in 3 domains (physiological consequences, alcohol
      related violence, and conflict/trouble) and the number of times in the past year
      they used 6 distinct drinking contexts (parties, restaurants/bars, parking
      lots/street corners, beaches/parks, respondent's home without parents, and
      someone else's home without parents). Context-specific dose-response model was
      estimated for each context using censored Tobit models with heteroskedasticity
      corrections. RESULTS: Physiological problems were associated with more frequent
      drinking in 5 of 6 contexts. Heavier drinking in restaurants/bars/nightclubs (b =
      0.22, SE = 0.10) and someone else's home without parents (b = 0.14, SE = 0.06)
      was associated with greater risk of violence. Conflict/trouble was associated
      with more frequent drinking in parking lots/street corners, declining at higher
      levels of drinking. CONCLUSIONS: Certain drinking contexts are related to
      problems among youths, some because they are associated with frequent alcohol
      consumption and others because they are associated with heavier drinking.
      Identifying which drinking contexts are related to specific alcohol-related
      problems and why is an essential component of developing effective preventive
      interventions.

PMID- 26208253
TI  - Altered Gravity Simulated by Parabolic Flight and Water Immersion Leads to
      Decreased Trunk Motion.
AB  - Gravity is one of the important environmental factors that influence the
      physiologies and behaviors of animals and humans, and changes in gravity elicit a
      variety of physiological and behavioral alterations that include impaired
      movement coordination, vertigo, spatial disorientation, and perceptual illusions.
      To elucidate the effects of gravity on human physiology and behavior, we examined
      changes in wrist and trunk activities and heart rate during parabolic flight and
      the activity of wrist and trunk in water immersion experiments. Data from 195
      person-time parabolas performed by eight subjects revealed that the trunk motion
      counts decreased by approximately half during ascending legs (hypergravity),
      relative to the data acquired before the parabolic flights. In contrast, the
      wrist activity remained unchanged. The results from the water immersion
      experiments demonstrated that in the underwater condition, both the wrist and
      trunk activities were significantly decreased but the latter decreased to a much
      lower level. Together, these data suggest that gravitational alterations can
      result in differential influences on the motions of the wrist and the trunk.
      These findings might be important for understanding the degeneration of skeleton
      and muscular system and performance of astronauts in microgravity. 

PMID- 26208255
TI  - Interfacial Activity and Contact Angle of Homogeneous, Functionalized, and Janus
      Nanoparticles at the Water/Decane Interface.
AB  - Surface heterogeneity affects the behavior of nanoparticles at liquid interfaces.
      To gain a deeper understanding on the details of these phenomena, we have
      measured the interfacial activity and contact angle at water/decane interfaces
      for three different types of nanoparticles: homogeneous poly(methyl methacrylate)
      (PMMA), silica functionalized with a capping ligand containing a methacrylate
      terminal group, and Ag-based Janus colloids with two capping ligands of different
      hydrophobicity. The interfacial activity was analyzed by pendant drop
      tensiometry, and the contact angle was measured directly by freeze-fracture
      shadow-casting cryo-scanning electron microscopy. The silver Janus nanoparticles
      presented the highest interfacial activity, compared to the silica nanoparticles
      and the homogeneous PMMA nanoparticles. Additionally, increasing the bulk
      concentration of the PMMA and silica nanoparticles up to 100-fold compared to the
      Janus nanoparticles led to silica particles forming fractal-like structures at
      the interface, contrary to the PMMA particles that did not show any spontaneous
      adsorption. 

PMID- 26208254
TI  - Dependence of DCE-MRI biomarker values on analysis algorithm.
AB  - BACKGROUND: Dynamic contrast-enhanced MRI (DCE-MRI) biomarkers have proven
      utility in tumors in evaluating microvascular perfusion and permeability, but it
      is unclear whether measurements made in different centers are comparable due to
      methodological differences. PURPOSE: To evaluate how commonly utilized analytical
      methods for DCE-MRI biomarkers affect both the absolute parameter values and
      repeatability. MATERIALS AND METHODS: DCE-MRI was performed on three consecutive
      days in twelve rats bearing C6 xenografts. Endothelial transfer constant
      (Ktrans), extracellular extravascular space volume fraction (ve), and contrast
      agent reflux rate constant (kep) measures were computed using: 2-parameter
      ("Tofts" or "standard Kety") vs. 3-parameter ("General Kinetic" or "extended
      Kety") compartmental models (including blood plasma volume fraction (vp) with 3
      parameter models); individual- vs. population-based vascular input functions
      (VIFs); and pixel-by-pixel vs. whole tumor-ROI. Variability was evaluated by
      within-subject coefficient of variation (wCV) and variance components analyses.
      RESULTS: DCE-MRI absolute parameter values and wCVs varied widely by analytical
      method. Absolute parameter values ranged, as follows, median Ktrans, 0.09-0.18
      min-1; kep, 0.51-0.92 min-1; ve, 0.17-0.23; and vp, 0.02-0.04. wCVs also varied
      widely by analytical method, as follows: mean Ktrans, 32.9-61.9%; kep, 11.6
      41.9%; ve, 16.1-54.9%; and vp, 53.9-77.2%. Ktrans and kep values were lower with
      3- than 2-parameter modeling (p<0.0001); kep and vp were lower with pixel- than
      whole-ROI analyses (p<0.0006). wCVs were significantly smaller for ve, and larger
      for kep, with individual- than population-based VIFs. CONCLUSIONS: DCE-MRI
      parameter values and repeatability can vary widely by analytical methodology.
      Absolute values of DCE-MRI biomarkers are unlikely to be comparable between
      different studies unless analyses are carefully standardized.

PMID- 26208256
TI  - 2D map projections for visualization and quantitative analysis of 3D fluorescence
      micrographs.
AB  - We introduce Map3-2D, a freely available software to accurately project up to
      five-dimensional (5D) fluorescence microscopy image data onto full-content 2D
      maps. Similar to the Earth's projection onto cartographic maps, Map3-2D unfolds
      surface information from a stack of images onto a single, structurally connected
      map. We demonstrate its applicability for visualization and quantitative analyses
      of spherical and uneven surfaces in fixed and dynamic live samples by using
      mammalian and yeast cells, and giant unilamellar vesicles. Map3-2D software is
      available at http://www.zmbh.uni
      heidelberg.de//Central_Services/Imaging_Facility/Map3-2D.html. 

PMID- 26208257
TI  - Potential Use of a Weak Ethylene Receptor Mutant, Sletr1-2, as Breeding Material
      To Extend Fruit Shelf Life of Tomato.
AB  - Mutations in the ethylene receptor gene (SlETR1), Sletr1-1 and Sletr1-2, are
      effective in reducing ethylene sensitivity and improving fruit shelf life. In
      this study the effect of Sletr1-1 and Sletr1-2 mutations was investigated in F1
      hybrid lines. These two mutants and control were crossed with four commercial
      pure-line tomatoes. The Sletr1-1 mutation showed undesirable pleiotropic effects
      in the F1 hybrid lines. The Sletr1-2 mutation was effective in improving fruit
      shelf life of F1 hybrid lines for 4-5 days longer. It was also effective in
      improving fruit firmness without change in fruit size, ethylene production,
      respiration rate, and total soluble solids or a great reduction in fruit color,
      lycopene, and beta-carotene, although the titratable acidity was increased by
      Sletr1-2 mutation. These results indicate that the Sletr1-2 mutant allele has the
      potential to improve fruit shelf life via incorporation in tomato breeding
      programs. 

PMID- 26208258
TI  - Patient Specific Hardware-in-the-Loop Testing of Cerebrospinal Fluid Shunt
      Systems.
AB  - GOAL: The development of increasingly sophisticated cerebrospinal fluid (CSF)
      shunts calls for test beds that can reproduce an ever larger range of physiologic
      and pathophysiologic behaviors. In particular, upcoming smart and active devices
      will require extensive testing under complex dynamic conditions. Herein, we
      describe a test bed that allows for fast, cost effective, and realistic in vitro
      testing of active and passive, gravitational and nongravitational CSF shunts
      based on the hardware-in-the-loop principle. METHODS: The shunt to be tested is
      placed in a dynamic in vitro setup that interfaces with a mathematical model of
      the patient's relevant physiology, which is evaluated numerically in real time.
      The model parameters can be identified using standard clinical tests. The test
      bed accounts for posture-dependent behavior and viscoelastic effects. RESULTS:
      Simulations of infusion tests, of intracranial pressure modulation by
      cardiovascular action, and of the effects of postural changes show good agreement
      with published results. Evaluation of valves without and with gravitational units
      show in modeled sitting patients the expected behavior of overdrainage and
      avoidance thereof, respectively. Finally, a 24-h test cycle based on recorded
      patient data elucidates the interaction between patient and shunt system
      expressed by drainage rate and intracranial pressure during typical daily
      activities. CONCLUSION: We envision this test bed as a tool to quantify a shunt's
      performance within a realistic yet reproducible testing environment.
      SIGNIFICANCE: The test bed can improve our understanding of the complex
      interaction between patient and shunt system and may catalyze the development of
      active shunts, while reducing the number of necessary in vivo experiments.

PMID- 26208260
TI  - A Wireless Fully Passive Neural Recording Device for Unobtrusive Neuropotential
      Monitoring.
AB  - GOAL: We propose a novel wireless fully passive neural recording device for
      unobtrusive neuropotential monitoring. Previous work demonstrated the feasibility
      of monitoring emulated brain signals in a wireless fully passive manner. In this
      paper, we propose a novel realistic recorder that is significantly smaller and
      much more sensitive. METHODS: The proposed recorder utilizes a highly efficient
      microwave backscattering method and operates without any formal power supply or
      regulating elements. Also, no intracranial wires or cables are required. In-vitro
      testing is performed inside a four-layer head phantom (skin, bone, gray matter,
      and white matter). RESULTS: Compared to our former implementation, the neural
      recorder proposed in this study has the following improved features: 1) 59%
      smaller footprint, 2) up to 20-dB improvement in neuropotential detection
      sensitivity, and 3) encapsulation in biocompatible polymer. CONCLUSION: For the
      first time, temporal emulated neuropotentials as low as 63 MUVpp can be detected
      in a wireless fully passive manner. Remarkably, the high-sensitivity achieved in
      this study implies reading of most neural signals generated by the human brain.
      SIGNIFICANCE: The proposed recorder brings forward transformational possibilities
      in wireless fully passive neural detection for a very wide range of applications
      (e.g., epilepsy, Alzheimer's, mental disorders, etc.).

PMID- 26208259
TI  - Theoretical Optimization of Stimulation Strategies for a Directionally Segmented
      Deep Brain Stimulation Electrode Array.
AB  - Programming deep brain stimulation (DBS) systems currently involves a clinician
      manually sweeping through a range of stimulus parameter settings to identify the
      setting that delivers the most robust therapy for a patient. With the advent of
      DBS arrays with a higher number and density of electrodes, this trial and error
      process becomes unmanageable in a clinical setting. This study developed a
      computationally efficient, model-based algorithm to estimate an electrode
      configuration that will most strongly activate tissue within a volume of
      interest. The cerebellar-receiving area of motor thalamus, the target for
      treating essential tremor with DBS, was rendered from imaging data and
      discretized into grid points aligned in approximate afferent and efferent axonal
      pathway orientations. A finite-element model (FEM) was constructed to simulate
      the volumetric tissue voltage during DBS. We leveraged the principle of voltage
      superposition to formulate a convex optimization-based approach to maximize
      activating function (AF) values at each grid point (via three different
      criteria), hence increasing the overall probability of action potential
      initiation and neuronal entrainment within the target volume. For both efferent
      and afferent pathways, this approach achieved global optima within several
      seconds. The optimal electrode configuration and resulting AF values differed
      across each optimization criteria and between axonal orientations. This approach
      only required a set of FEM simulations equal to the number of DBS array
      electrodes, and could readily accommodate anisotropic-inhomogeneous tissue
      conductances or other axonal orientations. The algorithm provides an efficient,
      flexible determination of optimal electrode configurations for programming DBS
      arrays. 

PMID- 26208261
TI  - Investigation of the Capture of Magnetic Particles From High-Viscosity Fluids
      Using Permanent Magnets.
AB  - GOAL: This paper investigates the practicality of using a small, permanent magnet
      to capture magnetic particles out of high-viscosity biological fluids, such as
      synovial fluid. METHODS: Numerical simulations are used to predict the trajectory
      of magnetic particles toward the permanent magnet. The simulations are used to
      determine a "collection volume" with a time-dependent size and shape, which
      determines the number of particles that can be captured from the fluid in a given
      amount of time. RESULTS: The viscosity of the fluid strongly influences the
      velocity of the magnetic particles toward the magnet, hence, the collection
      volume after a given time. In regards to the design of the magnet, the overall
      size is shown to most strongly influence the collection volume in comparison to
      the magnet shape or aspect ratio. CONCLUSION: Numerical results showed good
      agreement with in vitro experimental magnetic collection results. SIGNIFICANCE:
      In the long term, this paper aims to facilitate optimization of the collection of
      magnetic particle-biomarker conjugates from high-viscosity biological fluids
      without the need to remove the fluid from a patient.

PMID- 26208262
TI  - Infrared Saliva Analysis of Psoriatic and Diabetic Patients: Similarities in
      Protein Components.
AB  - GOAL: Psoriasis is a chronic skin disease which is very common in the population
      and requires frequent clinical and pharmacological treatment. In the following, a
      study based on Fourier transform infrared spectroscopy analyzing saliva proteomic
      components in psoriatic patients against diabetic patients and a control group is
      presented. Clinical analysis showed a prominent amide II band, at around 1545 cm(
      1), and the composition of the amide I band, at around 1647 cm(-1), allowing us
      to distinguish the infrared salivary signature of psoriatic and diabetic patients
      from the control group and even from patients with different kinds of psoriasis.
      Moreover, results highlighted existing differences in the secondary structure
      composition of proteins between psoriatic and diabetic patients as compared to
      the control group. In fact, the saliva spectra of the control group and that of
      the palmoplantar psoriatic patients differ from plaque psoriasis and diabetic
      patient spectra because of the absence of the amide II band and the presence of
      different secondary protein-structure conformations.

PMID- 26208263
TI  - A Grouped Up-and-Down Method Used for Efficacy Comparison Between Two Different
      Defibrillation Waveforms.
AB  - Electrical defibrillation, which consists of delivering a therapeutic dose of the
      electrical current to the fibrillating heart with the aid of a defibrillator, is
      still the only effective way to treat life-threatening ventricular fibrillation
      (VF). However, the efficacy of electrical therapy for terminating VF is highly
      dependent on the waveform applied. When new defibrillation waveforms or
      techniques are developed, their efficacy needs to be accurately evaluated and
      compared to those in use. A common method for the comparison of defibrillation
      efficacy is to estimate and compare the individual defibrillation threshold (DFT)
      by constructing dose response curves or using an up-and-down method. Since DFT is
      calculated by repetitive and sequential shocks, there will be variability for
      each measurement and for each individual. This creates a considerable uncertainty
      for paired comparison. In this paper, a novel grouped up-and-down method is
      developed for the comparison of defibrillation efficacy between two different
      defibrillation waveforms or techniques. The efficacy of two commonly used
      biphasic defibrillation waveforms was compared in a porcine model of cardiac
      arrest using the developed method. Experimental results demonstrate that the
      proposed method is more sensitive for efficacy comparison and requires less
      defibrillation attempts compared with traditional DFT methods. 

PMID- 26208264
TI  - An Ear-Worn Vital Signs Monitor.
AB  - This paper presents a wearable vital signs monitor at the ear. The monitor
      measures the electrocardiogram (ECG), ballistocardiogram (BCG), and
      photoplethysmogram (PPG) to obtain pre-ejection period (PEP), stroke volume (SV),
      cardiac output (CO), and pulse transit time (PTT). The ear is demonstrated as a
      natural anchoring point for the integrated sensing of physiological signals. All
      three signals measured can be used to obtain heart rate (HR). Combining the ECG
      and BCG allows for the estimation of the PEP, while combining the BCG and PPG
      allows for the measurement of PTT. Additionally, the J-wave amplitude of the BCG
      is correlated with the SV and, when combined with HR, yields CO. Results from a
      clinical human study on 13 subjects demonstrate this proof-of-concept device. 

PMID- 26208265
TI  - Questionnaires Designed to Assess Knowledge of Heart Failure Patients: A
      Systematic Review.
AB  - BACKGROUND: The objectives of this systematic review were (1) to describe the
      psychometric properties of questionnaires designed to assess knowledge of heart
      failure (HF) patients and (2) to identify the most applicable questionnaire to
      assess knowledge of HF patients. METHODS: A literature search of electronic
      databases was conducted from database inception to March 2014. Eligible articles
      included studies describing the development and psychometric testing of
      questionnaires designed to assess HF patients' knowledge. Outcomes were based on
      the quality criteria for measurement properties of health status questionnaires.
      Articles were considered for inclusion by 2 authors independently. RESULTS:
      Overall, 12 articles were included, of which 4 (33.33%) were considered "good"
      quality. Twelve original English-language instruments were identified. Content
      validity was described in 10 studies and presented positive ratings in all of
      them (83.33%); internal consistency in 10 studies and positive ratings in 5
      (41.66%); construct validity in 5 and positive ratings in 4 (33.33%);
      responsiveness in 3 and positive ratings in 2 (16.66%); and reproducibility and
      floor effects in 1 with positive ratings. Based on our criteria, the Atlanta HF
      Knowledge Test was identified as the most applicable questionnaire to assess
      knowledge of HF patients. CONCLUSION: Psychometric properties of questionnaires
      assessing HF patients' knowledge are poorly described in the literature. Although
      we identified the Atlanta HF Knowledge Test as the most promising instrument, it
      has methodological limitations. We recommend the researchers to use the
      questionnaire that best serves their research question and context.

PMID- 26208266
TI  - Incidence of adrenal crisis in patients with adrenal insufficiency.
AB  - BACKGROUND: An adrenal crisis (AC) is a potential life-threatening event in
      patients with adrenal insufficiency (AI). This study aims to determine the
      incidence, causes, and risk factors of AC in AI. METHODS: Patients with AI
      diagnosed and treated at the University Medical Center Utrecht for the past 30
      years were identified, and all medical records were assessed by two independent
      investigators. The observed frequency of AC was determined as incidence rate,
      calculated as the number of AC divided by person-years (PY). In addition,
      precipitating factors and risk factors were assessed. RESULTS: We observed an
      incidence rate of 5.2 AC (95% CI 4.3-6.3) per 100 PY in primary adrenal
      insufficiency (PAI, a total of 111 patients), and 3.6 AC (95% CI 3.1-4.1) per 100
      PY in secondary adrenal insufficiency (SAI a total of 319 patients). Patients
      with an established diagnosis of tertiary (glucocorticoid-induced) adrenal
      insufficiency (a total of 28 patients) had 15.1 AC (95% CI 11.0-19.9) per 100 PY.
      The most important risk factor was the existence of comorbidity. Gastro-enteritis
      and other infections were the most common precipitating factors for AC.
      CONCLUSION: AC still occurs relatively frequent in patients with AI, mostly
      precipitated by infections and particularly in patients with high comorbidity.
      This should be taken into account in the education and follow-up of patients with
      AI.

PMID- 26208268
TI  - Fingerprints of polycyclic aromatic hydrocarbons (PAHs) in infrared absorption
      spectroscopy.
AB  - We have analyzed a set of 51 PAHs whose structures have been hypothesized from
      mass spectrometry data collected on samples extracted from carbon particles of
      combustion origin. We have obtained relationships between infrared absorption
      signals in the fingerprint region (mid-IR) and the chemical structures of PAHs,
      thus proving the potential of IR spectroscopy for the characterization of the
      molecular structure of aromatic combustion products. The results obtained here
      for the spectroscopic characterization of PAHs can be also of interest in
      Materials Science and Astrophysics.

PMID- 26208267
TI  - Role of TRPV1 in the Differentiation of Mouse Embryonic Stem Cells into
      Cardiomyocytes.
AB  - Cytosolic Ca2+ ([Ca2+]i) is an important signal that regulates cardiomyocyte
      differentiation during cardiogenesis. TRPV1 is a Ca2+-permeable channel that is
      expressed in cardiomyocytes. In the present study, we utilized mouse embryonic
      stem cell-derived cardiomyocytes (mESC-CMs) as a model to investigate the
      functional role of TRPV1 in cardiomyocyte differentiation. Induction of embryonic
      stem cells into cardiomyocytes was achieved using embryoid body (EB)-based
      differentiation method. Quantitative PCRs showed an increased TRPV1 expression
      during the differentiation process. In [Ca2+]i measurement study, application of
      TRPV1 agonists, capsaicin and camphor, elicited a [Ca2+]i rise in mESC-CMs, the
      effect of which was abolished by TRPV1-shRNA. In functional study, treatment of
      EBs with TRPV1 antagonists (capsazepine and SB366791) and TRPV1-shRNA reduced the
      size of the EBs and decreased the percentage of spontaneously beating EBs. TRPV1
      antagonists and TRPV1-shRNA also suppressed the expression of cardiomyocyte
      marker genes, including cardiac actin, c-TnT, c-TnI, and alpha-MHC. Taken
      together, this study demonstrated an important functional role of TRPV1 channels
      in the differentiation of mESCs into cardiomyocytes. 

PMID- 26208269
TI  - Solvent scales used to study the intermolecular interactions in binary solutions
      of two p-aryl-pyridazinium methylids.
AB  - The visible electronic absorption band with intramolecular charge transfer of two
      pyridazinium ylids having common carbanion and different heterocycles is recorded
      in solutions and its position is correlated to parameters of some empirical
      scales of solvents. The nature of the intermolecular interactions in pyridazinium
      ylid solutions is discussed and the supply of each type of interaction is
      established based on solvatochromic study.

PMID- 26208270
TI  - In-situ synthesis of high stable CdS quantum dots and their application for
      photocatalytic degradation of dyes.
AB  - Photocatalysis based on semiconductor quantum dots, which utilize the solar
      energy can be used for elimination of pollutants from aqueous media and applied
      for water purification. In this paper, high stable CdS quantum dots (QDs) with
      good optical properties were successfully synthesized in a facile in-situ method,
      using Na2S2O3 as precursor and thioglycolic acid (TGA) as a catalyst, as well as
      capping agent in aqueous media. The synthesis process was optimized with a 2IV(7
      3) fractional factorial design method. Then, we studied the degradation of some
      industrial dyes including: alizarin, acid violet, mordant red and thymol blue as
      a tool to check the photocatalytic activity of synthesized CdS QDs. Results
      specified that the synthesized CdS QDs are capable for degradation of organic
      dyes under visible light irradiation with good recycling stability during
      photocatalytic experiments. Structural and spectroscopic properties of the
      synthesized CdS QDs were studied by TEM, XRD and absorption and fluorescence
      spectroscopy techniques. The synthesized TGA-capped CdS QDs have sizes in the
      range of 2.65-2.93nm with cubic crystalline structures.

PMID- 26208271
TI  - Synthesis of a novel 4H-pyran analog as minor groove binder to DNA using ethidium
      bromide as fluorescence probe.
AB  - In the present work, isopropyl-6-amino-4-(3,5-bis(trifluoromethyl)phenyl)-5-cyano
      2-methyl-4H-pyran-3-carboxylate (4H-pyran analog) has been synthesized by a three
      component reaction catalyzed by CsOH/gamma-Al2O3 and characterized. The
      interaction of 4H-pyran analog with herring sperm DNA (hs DNA) under
      physiological conditions (phosphate buffer of pH 7.2) was investigated by UV
      absorption, FT-IR, fluorescence, (31)P NMR and circular dichroism (CD)
      spectroscopy. Fluorescence quenching results reveal that static quenching
      mechanism is involved in binding between 4H-pyran analog and hs DNA. The
      calculated thermodynamic parameters (DeltaH degrees  and DeltaS degrees )
      indicate that hydrogen bonding plays a major role in binding between them. UV
      absorption and fluorescence shows the binding mode of 4H-pyran analog with hs DNA
      as non-intercalative. According to the IR spectroscopy, 4H-pyran analog binds to
      guanine, thymine, adenine bases of hs DNA but not to phosphate backbone of hs DNA
      which is also in good agreement with (31)P NMR results. CD and competitive
      binding experiment results confirms the minor groove binding of 4H-pyran analog
      to hs DNA.

PMID- 26208272
TI  - Up/down conversion luminescence and charge compensation investigation of Ca0.5Y1
      x(WO4)2:xLn(3+) (Ln=Pr, Sm, Eu, Tb, Dy, Yb/Er) phosphors.
AB  - Microstructures of Ca0.5Y(1-x)(WO4)2:xLn(3+) (Ln=Pr, Sm, Eu, Tb, Dy, Yb/Er)
      phosphors were prepared via the solid-state reaction method. X-ray diffraction,
      scanning electron microscopy and photoluminescence were used to characterize the
      prepared phosphor samples. The results reveal that the phosphor samples have
      single phase scheelite structures with tetragonal symmetry of I41/a. The down/up
      conversion photoluminescence of the Ca0.5Y(1-x)(WO4)2:xLn(3+) (Ln=Pr, Sm, Eu, Tb,
      Dy, Yb/Er) phosphors properties reveal characteristic visible emissions. The
      energy transfer process, fluorescence lifetime and color coordinates are
      discussed in detail. Furthermore, the phosphor Ca0.5Y(1-x)(WO4)2:xPr(3+) co-doped
      with alkali chlorides shows the enhancement of luminescence, which was found in
      the sodium chloride co-doped powder phosphor. The photometric characteristics
      indicate the suitability of the inorganic powder phosphors for solid-state
      lighting and display applications.

PMID- 26208274
TI  - Distribution of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
      Mutations in a Cohort of Patients Residing in Palestine.
AB  - Cystic fibrosis (CF) is an autosomal recessive inherited life-threatening
      disorder that causes severe damage to the lungs and the digestive system. In
      Palestine, mutations in the Cystic Fibrosis Transmembrane Conductance Regulator
      gene (CFTR) that contributes to the clinical presentation of CF are ill defined.
      A cohort of thirty three clinically diagnosed CF patients from twenty one
      different Palestinian families residing in the central and southern part of
      Palestine were incorporated in this study. Sweat chloride testing was performed
      using the Sweat Chek Conductivity Analyzer (ELITECH Group, France) to confirm the
      clinical diagnosis of CF. In addition, nucleic acid from the patients' blood
      samples was extracted and the CFTR mutation profiles were assessed by direct
      sequencing of the CFTR 27 exons and the intron-exon boundaries. For patient's DNA
      samples where no homozygous or two heterozygous CFTR mutations were identified by
      exon sequencing, DNA samples were tested for deletions or duplications using
      SALSA MLPA probemix P091-D1 CFTR assay. Sweat chloride testing confirmed the
      clinical diagnosis of CF in those patients. All patients had NaCl conductivity
      >60 mmol/l. In addition, nine different CFTR mutations were identified in all 21
      different families evaluated. These mutations were c.1393-1G>A, F508del, W1282X,
      G85E, c.313delA, N1303K, deletion exons 17a-17b-18, deletion exons 17a-17b and
      Q1100P. c.1393-1G>A was shown to be the most frequent occurring mutation among
      tested families. We have profiled the underling mutations in the CFTR gene of a
      cohort of 21 different families affected by CF. Unlike other studies from the
      Arab countries where F508del was reported to be the most common mutation, in
      southern/central Palestine, the c.1393-1G>A appeared to be the most common.
      Further studies are needed per sample size and geographic distribution to account
      for other possible CFTR genetic alterations and their frequencies.
      Genotype/phenotype assessments are also recommended and finally carrier frequency
      should be ascertained.

PMID- 26208276
TI  - Correction: Regulation of Adipogenesis and Key Adipogenic Gene Expression by 1,
      25-Dihydroxyvitamin D in 3T3-L1 Cells.

PMID- 26208275
TI  - Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to
      Adult Correlate Inversely with Cellular Proliferation.
AB  - Tardigrades are highly tolerant to desiccation and ionizing radiation but the
      mechanisms of this tolerance are not well understood. In this paper, we report
      studies on dose responses of adults and eggs of the tardigrade Hypsibius
      dujardini exposed to gamma radiation. In adults the LD50/48h for survival was
      estimated at ~ 4200 Gy, and doses higher than 100 Gy reduced both fertility and
      hatchability of laid eggs drastically. We also evaluated the effect of radiation
      (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of
      development, and observed a reduced hatchability in the early stage, while no
      effect was found in the late stage of development. Survival of juveniles from
      irradiated eggs was highly affected by a 500 Gy dose, both in the early and the
      late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed
      into adults and produced offspring, but their fertility was reduced compared to
      the controls. Finally we measured the effect of low temperature during
      irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed
      a slight delay in the expressed mortality when tardigrades were irradiated on
      ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to
      desiccation compared to limno-terrestrial tardigrades, the high radiation
      tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and
      seems to challenge the idea that desiccation and radiation tolerance rely on the
      same molecular mechanisms. We suggest that the higher radiation tolerance in
      adults and late stage embryos of H. dujardini (and in other studied tardigrades)
      compared to early stage embryos may partly be due to limited mitotic activity,
      since tardigrades have a low degree of somatic cell division (eutely), and
      dividing cells are known to be more sensitive to radiation. 

PMID- 26208277
TI  - Investigation into the Antigenic Properties and Contributions to Growth in Blood
      of the Meningococcal Haemoglobin Receptors, HpuAB and HmbR.
AB  - Acquisition of iron from host complexes is mediated by four surface-located
      receptors of Neisseria meningitidis. The HmbR protein and heterodimeric HpuAB
      complex bind to haemoglobin whilst TbpBA and LbpBA bind iron-loaded transferrin
      and lactoferrin complexes, respectively. The haemoglobin receptors are unevenly
      distributed; disease-causing meningococcal isolates encode HmbR or both receptors
      while strains with only HpuAB are rarely-associated with disease. Both these
      receptors are subject to phase variation and 70-90% of disease isolates have one
      or both of these receptors in an ON expression state. The surface-expression,
      ubiquity and association with disease indicate that these receptors could be
      potential virulence factors and vaccine targets. To test for a requirement during
      disease, an hmbR deletion mutant was constructed in a strain (MC58) lacking HpuAB
      and in both a wild-type and TbpBA deletion background. The hmbR mutant exhibited
      an identical growth pattern to wild-type in whole blood from healthy human donors
      whereas growth of the tbpBA mutant was impaired. These results suggest that
      transferrin is the major source of iron for N. meningitidis during replication in
      healthy human blood. To examine immune responses, polyclonal antisera were raised
      against His-tagged purified-recombinant variants of HmbR, HpuA and HpuB in mice
      using monolipopolysaccharide as an adjuvant. Additionally, monoclonal antibodies
      were raised against outer membrane loops of HmbR presented on the surface of
      EspA, an E. coli fimbrial protein. All antisera exhibited specific reactivity in
      Western blots but HmbR and HpuA polyclonal sera were reactive against intact
      meningococcal cells. None of the sera exhibited bactericidal activity against
      iron-induced wild-type meningococci. These findings suggest that the HmbR protein
      is not required during the early stages of disease and that immune responses
      against these receptors may not be protective. 

PMID- 26208278
TI  - A Novel TGR5 Activator WB403 Promotes GLP-1 Secretion and Preserves Pancreatic
      beta-Cells in Type 2 Diabetic Mice.
AB  - The G protein-coupled receptor TGR5 is a membrane receptor for bile acids. Its
      agonism increases energy expenditure and controls blood glucose through secretion
      of glucagon-like peptide-1 in enteroendocrine cells. In this study, we explored
      the therapeutic potential of WB403, a small compound activating TGR5 which was
      identified by combining TGR5 targeted luciferase assay and active GLP-1 assay, in
      treating type 2 diabetes. After confirmation of TGR5 and GLP-1 stimulating
      activities in various cell systems, WB403 was examined in oral glucose tolerance
      test, and tested on different mouse models of type 2 diabetes for glycemic
      control and pancreatic beta-cell protection effect. As a result, WB403 exhibited
      a moderate TGR5 activation effect while promoting GLP-1 secretion efficiently.
      Interestingly, gallbladder filling effect, which was reported for some known TGR5
      agonists, was not detected in this novel compound. In vivo results showed that
      WB403 significantly improved glucose tolerance and decreased fasting blood
      glucose, postprandial blood glucose and HbA1c in type 2 diabetic mice. Further
      analysis revealed that WB403 increased pancreatic beta-cells and restored the
      normal distribution pattern of alpha-cell and beta-cell in islets. These findings
      demonstrated that TGR5 activator WB403 effectively promoted GLP-1 release,
      improved hyperglycemia and preserved the mass and function of pancreatic beta
      cells, whereas it did not show a significant side effect on gallbladder. It may
      represent a promising approach for future type 2 diabetes mellitus drug
      development. 

PMID- 26208279
TI  - Immunohistochemistry and Fluorescence In Situ Hybridization Can Inform the
      Differential Diagnosis of Low-Grade Noninvasive Urothelial Carcinoma with an
      Inverted Growth Pattern and Inverted Urothelial Papilloma.
AB  - Urothelial carcinoma (UC) comprises a heterogeneous group of epithelial neoplasms
      with diverse biological behaviors and variable clinical outcomes. Distinguishing
      UC histological subtypes has become increasingly important because prognoses and
      therapy can dramatically differ among subtypes. In clinical work, overlapping
      morphological findings between low-grade noninvasive UC (LGNUC), which exhibits
      an inverted growth pattern, and inverted urothelial papilloma (IUP) can make
      subclassification difficult. We propose a combination of immunohistochemistry
      (IHC) and molecular cytogenetics for subtyping these clinical entities. In our
      study, tissue microarray immunohistochemical profiles of Ki-67, p53, cytokeratin
      20 (CK20) and cyclinD1 were assessed. Molecular genetic alterations such as the
      gain of chromosomes 3, 7 or 17 or the homozygous loss of 9p21 were also assessed
      for their usefulness in differentiating these conditions. Based on our analysis,
      Ki-67 and CK20 may be useful for the differential diagnosis of these two tumor
      types. Fluorescence in situ hybridization (FISH) can also provide important data
      in cases in which the malignant nature of an inverted urothelial neoplasm is
      unclear. LGNUC with an inverted growth pattern that is negative for both Ki-67
      and CK20 can be positively detected using FISH. 

PMID- 26208280
TI  - Depletion of enteroendocrine and mucus-secreting cells is associated with
      colorectal carcinogenesis severity and impaired intestinal motility in rats.
AB  - This study investigated the relationship between enteroendocrine and mucus
      secreting cells distribution, the severity of colonic mucosal injury and
      intestinal motility in experimental colorectal carcinogenesis. Using a
      standardized murine model of colorectal carcinogenesis, eight-weeks-old female
      Wistar rats weighting 147.30 +/- 29.15g were randomized into two groups receiving
      a subcutaneous injection of 0.9% saline (control) or the chemical carcinogen 1,2
      dimethylhydrazine (DMH) at 20 mg/kg per week during 10 weeks. Aberrant crypt foci
      (ACF) were more frequent in DMH group compared to control group (P < 0.001). The
      number of enteroendocrine and mucus-secreting cells, and intestinal motility was
      reduced in DMH animals (P < 0.05). The distribution of enteric neurons was
      similar in both groups. In DMH animals there was a direct correlation between
      colonic motility and distribution of enteroendocrine (R(2)  = 0.68, P < 0.05) and
      mucus-secreting cells (R(2)  = 0.77, P < 0.05). Inverse correlation between the
      number of ACF, mucus-secreting cells (R(2)  = -0.57, P < 0.05), and
      enteroendocrine cells (R(2)  = -0.74, P < 0.05) was also observed. There was
      inverse correlation between the severity of the mucosal lesion, the number of
      mucus-secreting cells (R(2)  = -0.83, P < 0.05) and enteroendocrine cells (R(2) 
      = -0.96, P < 0.05). There was a direct correlation between nucleolar organizer
      regions (AgNOR) and ACF number (R(2)  = 0.62; P < 0.01). Inverse correlation was
      also found between AgNOR, the number of mucus-secreting cells (R(2)  = -0.76; P <
      0.001), and enteroendocrine cells (R(2)  = -0.86; P < 0.001). Taken together, the
      results indicated that colonic malignant transformation is related to depletion
      of mucus-secreting and enteroendocrine cells, which was a useful indicator of the
      evolutionary status of intestinal neoplasm, partially explaining the intestinal
      motility disorders in the early stages of colorectal carcinogenesis.

PMID- 26208281
TI  - The Genomic Contributions of Avian H1N1 Influenza A Viruses to the Evolution of
      Mammalian Strains.
AB  - Among the influenza A viruses (IAVs) in wild aquatic birds, only H1, H2, and H3
      subtypes have caused epidemics in humans. H1N1 viruses of avian origin have also
      caused 3 of 5 pandemics. To understand the reappearance of H1N1 in the context of
      pandemic emergence, we investigated whether avian H1N1 IAVs have contributed to
      the evolution of human, swine, and 2009 pandemic H1N1 IAVs. On the basis of
      phylogenetic analysis, we concluded that the polymerase gene segments (especially
      PB2 and PA) circulating in North American avian H1N1 IAVs have been reintroduced
      to swine multiple times, resulting in different lineages that led to the
      emergence of the 2009 pandemic H1N1 IAVs. Moreover, the similar topologies of
      hemagglutinin and nucleoprotein and neuraminidase and matrix gene segments
      suggest that each surface glycoprotein coevolved with an internal gene segment
      within the H1N1 subtype. The genotype of avian H1N1 IAVs of Charadriiformes
      origin isolated in 2009 differs from that of avian H1N1 IAVs of Anseriformes
      origin. When the antigenic sites in the hemagglutinin of all 31 North American
      avian H1N1 IAVs were considered, 60%-80% of the amino acids at the antigenic
      sites were identical to those in 1918 and/or 2009 pandemic H1N1 viruses. Thus,
      although the pathogenicity of avian H1N1 IAVs could not be inferred from the
      phylogeny due to the small dataset, the evolutionary process within the H1N1 IAV
      subtype suggests that the circulation of H1N1 IAVs in wild birds poses a
      continuous threat for future influenza pandemics in humans. 

PMID- 26208282
TI  - Influence of Environmental Governance on Deforestation in Municipalities of the
      Brazilian Amazon.
AB  - It has been argued that measuring governance at scales smaller than global could
      be an important management tool. However, current studies are conducted on a
      global scale and use expensive methods. In the present study, we assess whether
      the reported governance of Amazonian municipalities is related to reductions in
      deforestation. Economic activity (EA) affected general governance (G) positively
      (G = 0.81 +1.19 * EA, F1, 98 = 77.36, p < 0.001). Environmental governance (EG)
      was not affected significantly (p = 0.43) by deforestation before 2000 (PD), but
      increased significantly (p < 0.001) with general governance (G) (EG = -0.29 +
      0.04 PD+0.98*OG, F2,97 = 42.6, p <0.001). Deforestation was not significantly
      related to environmental governance (p = 0.82). The only indirect effect of
      significant magnitude was the effect of the density of forest reserves on recent
      deforestation through deforestation before 2000, which was strongly negative (
      0.49). It is possible to assess reported actions to promote municipal governance
      through official data. However, it is not enough to assume that general
      governance or environmental governance at the municipal level, as reflected in
      the official statistics, benefits environmental conservation. In fact, even at
      the level of nation states, at which most quantification of governance has been
      undertaken, it seems that the relationship between governance and environmental
      preservation is only an assumption, because we are aware of no study that
      supports that hypothesis quantitatively. 

PMID- 26208284
TI  - Correction: Hyperspectral Imaging for Mapping of Total Nitrogen Spatial
      Distribution in Pepper Plant.

PMID- 26208283
TI  - Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and
      Vascular Destabilization.
AB  - AIMS: Branch retinal vein occlusion (BRVO) leads to extensive vascular remodeling
      and is important cause of visual impairment. Although the vascular morphological
      changes following experimental vein occlusion have been described in a variety of
      models using angiography, the underlying cellular events are ill defined. METHODS
      AND RESULTS: We here show that laser-induced experimental BRVO in mice leads to a
      wave of TUNEL-positive endothelial cell (EC) apoptosis in the upstream vascular
      network associated with a transient edema and hemorrhages. Subsequently, we
      observe an induction of EC proliferation within the dilated vein and capillaries,
      detected by EdU incorporation, and the edema resolves. However, the pericytes of
      the upstream capillaries are severely reduced, which was associated with
      continuing EC apoptosis and proliferation. The vascular remodeling was associated
      with increased expression of TGFbeta, TSP-1, but also FGF2 expression. Exposure
      of the experimental animals to hypoxia, when pericyte (PC) dropout had occurred,
      led to a dramatic increase in endothelial cell proliferation, confirming the
      vascular instability induced by the experimental BRVO. CONCLUSION: Experimental
      BRVO leads to acute endothelial cells apoptosis and increased permeability.
      Subsequently the upstream vascular network remains destabilized, characterized by
      pericyte dropout, un-physiologically high endothelial cells turnover and
      sensitivity to hypoxia. These early changes might pave the way for capillary loss
      and subsequent chronic ischemia and edema that characterize the late stage
      disease.

PMID- 26208285
TI  - Global histone modifications in Fumonisin B1 exposure in rat kidney epithelial
      cells.
AB  - Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in maize-based
      food and feed. Although the effects of FB1 on sphingolipid metabolism are clear,
      little is known about early molecular changes associated with FB1
      carcinogenicity. It has been shown that FB1 disrupts DNA methylation and
      chromatin modifications in HepG2 cells. We investigated dose- and time-dependent
      effects of FB1 in global histone modifications such as histone H3 lysine 9 di-,
      trimethylation (H3K9me2/me3), histone H3 lysine 4 trimethylation (H3K4me3),
      histone H4 lysine 20 trimethylation (H4K20me3), histone H3 lysine 9 acetylation
      (H3K9ac) and the enzymes involved in these mechanisms in rat kidney epithelial
      cells (NRK-52E). The increased levels of global H3K9me2/me3 were observed in FB1
      treated cells, while the global levels of H4K20me3 and H3K9ac were decreased. FB1
      caused some changes on the activities of H3K9 histone methyltransferase (HMT) and
      histone acetyltransferase (HAT) at high concentrations in NRK-52E cells. Further,
      the effects of trichostatin A (TSA), a histone deacetylase inhibitor, were
      investigated in NRK-52E cells. TSA was found to cause an increase on H3K9ac
      levels as expected. In this study we suggest that FB1 may disrupt epigenetic
      events by altering global histone modifications, introducing a novel aspect on
      the potential mechanism of FB1 carcinogenesis. 

PMID- 26208286
TI  - A novel micronucleus in vitro assay utilizing human hematopoietic stem cells.
AB  - The induction of micronucleated reticulocytes in the bone marrow is a sensitive
      indicator of chromosomal damage. Therefore, the micronucleus assay in rodents is
      widely used in genotoxicity and carcinogenicity testing. A test system based on
      cultured human primary cells could potentially provide better prediction compared
      to animal tests, increasing patient safety while also implementing the 3Rs
      principle, i.e. replace, reduce and refine. Hereby, we describe the development
      of an in vitro micronucleus assay based on animal-free ex vivo culture of human
      red blood cells from hematopoietic stem cells. To validate the method, five
      clastogens with direct action, three clastogens requiring metabolic activation,
      four aneugenic and three non-genotoxic compounds have been tested. Also,
      different metabolic systems have been applied. Flow cytometry was used for
      detection and enumeration of micronuclei. Altogether, the results were in
      agreement with the published data and indicated that a sensitive and cost
      effective in vitro assay to assess genotoxicity with a potential to high
      throughput screening has been developed. 

PMID- 26208287
TI  - Intraamniotic Inflammation in Women with Preterm Prelabor Rupture of Membranes.
AB  - OBJECTIVE: To characterize subgroups of preterm prelabor rupture of membranes
      (PPROM) and short-term neonatal outcomes based on the presence and absence of
      intraamniotic inflammation (IAI) and/or microbial invasion of the amniotic cavity
      (MIAC). METHODS: One hundred and sixty-six Caucasian women with singleton
      pregnancies were included in this study. Amniotic fluid samples were obtained by
      transabdominal amniocentesis (n=166) and were assayed for interleukin-6 levels by
      a lateral flow immunoassay. The presence of Ureaplasma species, Mycoplasma
      hominis, Chlamydia trachomatis, and 16S rRNA was evaluated in the amniotic fluid.
      IAI was defined as amniotic fluid IL-6 values, measured by a point of care test,
      higher than 745 pg/mL. RESULTS: Microbial-associated IAI (IAI with MIAC) and
      sterile intraamniotic inflammation (IAI alone) were found in 21% and 4%,
      respectively, of women with PPROM. Women with microbial-associated IAI had higher
      microbial loads of Ureaplasma species in the amniotic fluid than women with MIAC
      alone. No differences in the short-term neonatal morbidity with respect to the
      presence of microbial-associated IAI, sterile IAI and MIAC alone were found after
      adjusting for the gestational age at delivery in women with PPROM. CONCLUSIONS:
      Microbial-associated but not sterile intraamniotic inflammation is common in
      Caucasian women with PPROM. The gestational age at delivery but not the presence
      of inflammation affects the short-term neonatal morbidity of newborns from PPROM
      pregnancies.

PMID- 26208288
TI  - Rh-catalyzed sequential oxidative C-H activation/annulation with geminal
      substituted vinyl acetates to access isoquinolines.
AB  - The concise synthesis of 3-substituted or non-C3-substituted isoquinolines
      through Rh-catalyzed sequential oxidative C-H activation/annulation with geminal
      substituted vinyl acetates was developed with good functional group tolerance.
      The protocol was successfully applied to the total synthesis of the natural
      product papaverine. 

PMID- 26208290
TI  - Risk-based strategy for outpatient pharmacy practice: Focus on opioids.
AB  - OBJECTIVES: To highlight the limitations of community pharmacy practice and to
      propose a system change by implementing a risk-assessment method and management
      strategy for opioids in this arena. DATA SOURCES: Selected by the author.
      SUMMARY: Numerous studies show that the U.S. health care system is subject to a
      high rate of drug misadventures involving primarily low therapeutic index drugs,
      especially opioids. Currently proposed approaches to managing opioids focus on
      access control, but without a broader consideration of patient-use problems that
      lead to morbidity and mortality. While pharmacists are well-trained health
      professionals, their primary focus has been on drug distribution rather than
      proper use. This article highlights the limitations in contemporary community
      pharmacy practice that likely contribute to the problem of opioid misuse and
      resultant morbidity. CONCLUSION: A new model of practice is proposed whereby the
      most dangerous agents such as opioids are preidentified for a more formalized
      risk-based strategy focused upon optimal patient education and required follow
      up.

PMID- 26208289
TI  - Reliability and Validity of the Beijing Version of the Montreal Cognitive
      Assessment in the Evaluation of Cognitive Function of Adult Patients with OSAHS.
AB  - BACKGROUND: The patients with obstructive sleep apnea hypopnea syndrome (OSAHS)
      tend to develop cognitive deficits, which usually go unrecognized, and can affect
      their daily life. The Beijing version of the Montreal cognitive assessment (MoCA
      BJ), a Chinese version of MoCA, has been used for the assessment of cognitive
      functions of OSAHS patients in clinical practice. So far, its reliability and
      validity have not been tested. This study examined the reliability and validity
      of MoCA-BJ in a cohort of adult OSAHS patients. METHODS: 152 OSAHS patients,
      ranging from mild, moderate to severe, 49 primary snoring subjects and 40 normal
      controls were evaluated for cognitive functions by employing both MoCA-BJ and the
      Mini Mental State Examination (MMSE). Forty of them were re-tested by MoCA-BJ 14
      days after the first test. Internal consistency, test-retest reliability,
      discriminate and concurrent validity of MoCA-BJ were analyzed. RESULTS: Internal
      consistency reliability by Cronbach's alpha was adequate (0.73). Intra-class
      correlation coefficient (ICC), an measure of test-retest reliability, was 0.87
      (P<0.001). The total MoCA-BJ scores were significant higher in normal controls
      than in OSAHS groups (p<0.05). The performances of visuospatial ability in severe
      OSAHS group were significantly weaker than in normal controls and primary snoring
      group. The performances of executive ability in severe OSAHS patients were weaker
      than in normal controls. An optimal cut-off between normal controls and non
      normal subjects was at 26 points (total MoCA score). Moreover, cut-off between
      non-severe and severe OSAHS was at 2 points on visuospatial subscale. Analysis of
      the correlation between MoCA total scores and MMSE total scores revealed a
      statistically significant, though relatively weak, correlation (r=0.41, P<0.05).
      CONCLUSION: In conclusion, our study showed that the Beijing version of the MoCA
      was reliable and stable. The MoCA-BJ was capable of detecting cognitive
      dysfunction by visuospatial and total MoCA-BJ score.

PMID- 26208291
TI  - The orientation of the transition dipole moments of a polyene antibiotic
      Amphotericin B under UV-VIS studies.
AB  - Amphotericin B (AmB) belongs to naturally occurring fluorescent antibiotics,
      commonly used in the treatment of life-threatening fungal infections. Open
      question regarding mechanism of action of this molecule calls for its orientation
      and organization studies in biomembranes. Here, we present studies on linear
      dichroism and fluorescence polarization of AmB embedded in isotropic and oriented
      poly(vinyl) alcohol films to characterize their transition dipole moments to low
      energy excited electronic transitions S1 (2 Ag(-)) and S2 (1 Bu(+)). The dichroic
      ratio and fluorescence anisotropy data were analyzed for stretched PVA films
      doped AmB. The results show that the transition moment for absorption makes an
      angle phi = 27 degrees  +/- 2 degrees  with the molecular axis of AmB defined by
      the film stretching direction. The angles between the absorption and emission
      transition moments have been found for both the low excited electronic states, S2
      (beta = 4 degrees  +/- 5 degrees ) and S1 (beta = 6 degrees  +/- 5 degrees ). The
      fluorescence anisotropy analysis from the S2 state reveals additional component
      assigned to antiparallel AmB dimeric structure.

PMID- 26208292
TI  - White matter hyperintensity burden in elderly cohort studies: The Sunnybrook
      Dementia Study, Alzheimer's Disease Neuroimaging Initiative, and Three-City
      Study.
AB  - Given the recent acknowledgement of the complex mixed pathologies that contribute
      to the clinical expression of dementia, various cohort studies have aimed to
      examine Alzheimer's disease and cerebrovascular disease as comorbid pathologies,
      with neuroimaging playing a central role in these studies. Using white matter
      hyperintensities (WMH) as a biomarker of cerebrovascular disease, we compared WMH
      burden between the Sunnybrook Dementia Study, the Alzheimer's Disease
      Neuroimaging Initiative (ADNI-1), the Three-City Study, and various other studies
      around the world. Based on our findings, it was evident that ADNI-1 had minimal
      WMH burden relative to other large studies that examine aging and dementia. This
      low WMH burden in ADNI-1 may be considered as both an advantage, representing a
      relatively "pure" sample with little confounding vasculopathy, and a
      disadvantage, as it limits generalizability to "real-world" patient populations
      with mixed pathologies and to nondemented groups with baseline vascular disease.
      We explore possible reasons for this distinction, including management of
      vascular risk factors, gaps in diagnostic criteria, and future directions for
      clinical research. 

PMID- 26208293
TI  - A caffeic acid mediated facile synthesis of silver nanoparticles with powerful
      anti-cancer activity.
AB  - Green synthesis, especially in biological processes, has gained more attention
      with increasing application of silver nanoparticles (AgNPs) in biomedical fields.
      However, the biologically synthesized AgNPs have been to be anomalous in size and
      shape in most cases, as well as exhibiting certain difficulties when used in
      therapy. We used caffeic acid, a naturally plant polyphenol, to prepare the AgNPs
      in the current study and also evaluated their anti-cancer activity against the
      human hepatoma HepG2 cells. Results showed that the AgNPs could rapidly and
      simply be synthesized using caffeic acid as both a reducing agent and stabilizer.
      The synthesized AgNPs possessed characteristics of having small size, narrow
      distribution and high surface negative charge, as well as being stable in aqueous
      solution. Furthermore, the AgNPs could enter cells and effectively inhibit
      viability of tumor cells via induction of apoptosis. In conclusion, a caffeic
      acid mediated facile method was successfully developed to prepare the AgNPs as a
      potential alternative agent for human hepatoma therapy. 

PMID- 26208294
TI  - Folate-polydiacetylene-liposome for tumor targeted drug delivery and fluorescent
      tracing.
AB  - A novel folate-polydiacetylene-liposome (FP-PL) with both targeted drug delivery
      and fluorescence tracing was prepared by thin film rehydration method. The
      simulated drug delivery was performed in Bcap-37 breast cancer cells and Hs578Bst
      normal cells in vitro. The internalization and distribution of FP-PLs in the
      cells were presented by fluorescence cell imaging. The results show that the FP
      PLs possess low cytotoxicity, good biocompatibility and better targeting
      efficiency in comparison to polydiacetylene-liposomes (P-PLs). 

PMID- 26208295
TI  - Oscillational motion properties of bacteria and polystyrene particles on a
      positively polarized substrate surface.
AB  - The oscillational motion of bacteria and non-biological particles on a positively
      polarized substrate surface were investigated in this study using several
      bacterial species (Staphylococcus epidermidis ATCC12228 and Pseudomonas
      aeruginosa PA14) and polystyrene particles (modified with sulfate or carboxylate)
      that have different cell/particle size, surface potential, surface ionizable
      functional group, and surface appendage with respect to the mean square
      displacement (MSD) and motion trajectory. The attractive/repulsive interactions
      between the bacteria/particle and a positively polarized substrate surface are
      further discussed with the results of the motion analysis based on the extended
      Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. As our major findings, all the
      bacterial species and particles showed oscillational motion, a kind of sub
      diffusive motion that is more limited than the Brownian motion of the suspended
      bacteria/particles, on a positively polarized substrate surface. However, the
      motion properties among the bacteria/particles were found to differ in motion
      radius and MSD. As the size and negative surface potential of the
      bacteria/particle got smaller, the oscillational motion became more active, which
      may result from a decrease in attractive interactions such as van der Waals
      interaction and electrostatic attractive interaction. In the case in which some
      surface functional group (e.g., sulfate group) contributed to the formation of a
      strong Lewis acid-base interaction, the oscillational motion was significantly
      reduced regardless of the surface potential of the particle. The bacterial
      surface appendages were found to have no influence in explaining motion
      differences between the bacteria and non-biological particle. 

PMID- 26208296
TI  - Bio-inspired multifunctional catecholic assembly for photo-programmable
      biointerface.
AB  - This article reports a novel multifunctional mussel-inspired zwitterionic
      catecholic assembly to form a photoresponsive biointerface. The assembly is the
      combination of the antifouling sulfobetaine and photocleavable o-nitrophenyl
      moieties into a molecule, becoming sulfobetaine nitrodopamine (SB-nDA). We
      demonstrated the formation of a compact thin SB-nDA film on TiO2 by using the pH
      transition approach. The film thickness, surface wettability and elemental
      composition were characterized using ellipsometry, contact angle goniometer,
      atomic force microscopy and X-ray photoelectron spectroscopy, respectively. The
      SB-nDA thin films can effectively resist adhesion of both Gram-positive
      Staphylococcus epidermidis and Gram-negative Pseudomonas aeruginosa by more than
      95% relative to bare TiO2. Quartz crystal microbalance with dissipation (QCM-D)
      sensor was employed for protein fouling tests, showing the comparable antifouling
      property of SB-nDA with thiol- or silane-based surface ligands. More importantly,
      the spatiotemporal control over the bioinertness by UV irradiation has been
      studied with bacterial and protein adsorption. Therefore, the catecholic
      chemistry can be used for programmable tailoring of interfacial properties,
      permitting potential application in light-guided targeting for nanomedicine.

PMID- 26208297
TI  - An undeniable need for recognition: What do you call a man who has undergone
      foreskin restoration? "Uncircumcised"? "Restored"? How about just BRAVE? A
      response to Hill (2015).

PMID- 26208298
TI  - Comparison of Depletion Strategies for the Enrichment of Low-Abundance Proteins
      in Urine.
AB  - Proteome analysis of complex biological samples for biomarker identification
      remains challenging, among others due to the extended range of protein
      concentrations. High-abundance proteins like albumin or IgG of plasma and urine,
      may interfere with the detection of potential disease biomarkers. Currently,
      several options are available for the depletion of abundant proteins in plasma.
      However, the applicability of these methods in urine has not been thoroughly
      investigated. In this study, we compared different, commercially available
      immunodepletion and ion-exchange based approaches on urine samples from both
      healthy subjects and CKD patients, for their reproducibility and efficiency in
      protein depletion. A starting urine volume of 500 MUL was used to simulate
      conditions of a multi-institutional biomarker discovery study. All depletion
      approaches showed satisfactory reproducibility (n=5) in protein identification as
      well as protein abundance. Comparison of the depletion efficiency between the
      unfractionated and fractionated samples and the different depletion strategies,
      showed efficient depletion in all cases, with the exception of the ion-exchange
      kit. The depletion efficiency was found slightly higher in normal than in CKD
      samples and normal samples yielded more protein identifications than CKD samples
      when using both initial as well as corresponding depleted fractions. Along these
      lines, decrease in the amount of albumin and other targets as applicable,
      following depletion, was observed. Nevertheless, these depletion strategies did
      not yield a higher number of identifications in neither the urine from normal nor
      CKD patients. Collectively, when analyzing urine in the context of CKD biomarker
      identification, no added value of depletion strategies can be observed and
      analysis of unfractionated starting urine appears to be preferable. 

PMID- 26208299
TI  - Optimal Route for Mesenchymal Stem Cells Transplantation after Severe
      Intraventricular Hemorrhage in Newborn Rats.
AB  - Recently, we showed that intracerebroventricular (IC) transplantation of human
      umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) significantly
      attenuates posthemorrhagic hydrocephalus (PHH) and brain damage after severe IVH
      in newborn rats. This study was performed to determine the optimal route for
      transplanting MSCs for severe IVH by comparing IC transplantation, intravenous
      (IV) transplantation, and IV transplantation plus mannitol infusion. Severe IVH
      was induced by injecting 100 uL of blood into each ventricle of Sprague-Dawley
      rats on postnatal day 4 (P4). After confirming severe IVH with brain magnetic
      resonance imaging (MRI) at P5, human UCB-derived MSCs were transplanted at P6 by
      an IC route (1*105), an IV route (5*105), or an IV route with mannitol infused.
      Follow-up brain MRIs and rotarod tests were performed. At P32, brain tissue
      samples were obtained for biochemical and histological analyses. Although more
      MSCs localized to the brain after IC than after IV delivery, both methods were
      equally effective in preventing PHH; attenuating impaired rotarod test;
      increasing the number of TUNEL-positive cells, inflammatory cytokines, and
      astrogliosis; and reducing corpus callosal thickness and myelin basic protein
      expression after severe IVH regardless of mannitol co-infusion. Despite the
      superior delivery efficacy with IC than with the IV route, both IC and IV
      transplantation of MSCs had equal therapeutic efficacy in protecting against
      severe IVH. These findings suggest that the less invasive IV route might be a
      good alternative for clinically unstable, very preterm infants that cannot
      tolerate a more invasive IC delivery of MSCs. 

PMID- 26208300
TI  - Departures from the Energy-Biodiversity Relationship in South African Passerines:
      Are the Legacies of Past Climates Mediated by Behavioral Constraints on
      Dispersal?
AB  - Legacies of paleoclimates in contemporary biodiversity patterns have mostly been
      investigated with global datasets, or with weakly dispersive organisms, and as a
      consequence been interpreted in terms of geographical or physical constraints. If
      paleoclimatic legacies also occurred at the regional scale in the distributions
      of vagile organisms within biomes, they would rather suggest behavioral
      constraints on dispersal, i.e., philopatric syndromes. We examined 1) the
      residuals of the regression between contemporary energy and passerine species
      richness in South African biomes and 2) phylogenetic dispersion of passerine
      assemblages, using occupancy models and quarter-degree resolution citizen science
      data. We found a northeast to southwest gradient within mesic biomes congruent
      with the location of Quaternary mesic refugia, overall suggesting that as
      distance from refugia increased, more clades were lacking from local assemblages.
      A similar but weaker pattern was detected in the arid Karoo Biomes. In mobile
      organisms such as birds, behavioral constraints on dispersal appear strong enough
      to influence species distributions thousands of years after historical range
      contractions. 

PMID- 26208301
TI  - A Structural Model of the Human alpha7 Nicotinic Receptor in an Open
      Conformation.
AB  - Nicotinic acetylcholine receptors (nAchRs) are ligand-gated ion channels that
      regulate chemical transmission at the neuromuscular junction. Structural
      information is available at low resolution from open and closed forms of an
      eukaryotic receptor, and at high resolution from other members of the same
      structural family, two prokaryotic orthologs and an eukaryotic GluCl channel.
      Structures of human channels however are still lacking. Homology modeling and
      Molecular Dynamics simulations are valuable tools to predict structures of
      unknown proteins, however, for the case of human nAchRs, they have been
      unsuccessful in providing a stable open structure so far. This is due to
      different problems with the template structures: on one side the homology with
      prokaryotic species is too low, while on the other the open eukaryotic GluCl
      proved itself unstable in several MD studies and collapsed to a dehydrated, non
      conductive conformation, even when bound to an agonist. Aim of this work is to
      obtain, by a mixing of state-of-the-art homology and simulation techniques, a
      plausible prediction of the structure (still unknown) of the open state of human
      alpha7 nAChR complexed with epibatidine, from which it is possible to start
      structural and functional test studies. To prevent channel closure we employ a
      restraint that keeps the transmembrane pore open, and obtain in this way a
      stable, hydrated conformation. To further validate this conformation, we run four
      long, unbiased simulations starting from configurations chosen at random along
      the restrained trajectory. The channel remains stable and hydrated over the whole
      runs. This allows to assess the stability of the putative open conformation over
      a cumulative time of 1 MUs, 800 ns of which are of unbiased simulation. Mostly
      based on the analysis of pore hydration and size, we suggest that the obtained
      structure has reasonable chances to be (at least one of the possible) structures
      of the channel in the open conformation. 

PMID- 26208303
TI  - Anticancer Activity of Apaziquone in Oral Cancer Cells and Xenograft Model:
      Implications for Oral Cancer Therapy.
AB  - Oral squamous cell carcinoma (OSCC) patients diagnosed in late stages have
      limited chemotherapeutic options underscoring the great need for development of
      new anticancer agents for more effective disease management. We aimed to
      investigate the anticancer potential of Apaziquone, [EOquin, USAN, E09, 3-hydroxy
      5- aziridinyl-1-methyl-2(1H-indole-4,7-dione)-prop-beta-en-alpha-ol], a pro-drug
      belonging to a class of anti-cancer agents called bioreductive alkylating agents,
      for OSCC. Apaziquone treatment inhibited cell proliferation and induced apoptosis
      in OSCC cells in vitro. Apaziquone treated OSCC cells showed increased activation
      of Caspase 9 and Caspase 3, and Poly (ADP ribose) polymerase (PARP) cleavage
      suggesting induction of apoptosis by apaziquone in oral cancer cells.
      Importantly, apaziquone treatment significantly reduced oral tumor xenograft
      volume in immunocompromised NOD/SCID/Crl mice without causing apparent toxicity
      to normal tissues. In conclusion, our in vitro and in vivo studies identified and
      demonstrated the pre-clinical efficacy of Apaziquone, as a potential novel anti
      cancer therapeutic candidate for oral cancer management. 

PMID- 26208302
TI  - The quest for restoring hearing: Understanding ear development more completely.
AB  - Neurosensory hearing loss is a growing problem of super-aged societies. Cochlear
      implants can restore some hearing, but rebuilding a lost hearing organ would be
      superior. Research has discovered many cellular and molecular steps to develop a
      hearing organ but translating those insights into hearing organ restoration
      remains unclear. For example, we cannot make various hair cell types and arrange
      them into their specific patterns surrounded by the right type of supporting
      cells in the right numbers. Our overview of the topologically highly organized
      and functionally diversified cellular mosaic of the mammalian hearing organ
      highlights what is known and unknown about its development. Following this
      analysis, we suggest critical steps to guide future attempts toward restoration
      of a functional organ of Corti. We argue that generating mutant mouse lines that
      mimic human pathology to fine-tune attempts toward long-term functional
      restoration are needed to go beyond the hope generated by restoring single hair
      cells in postnatal sensory epithelia. 

PMID- 26208304
TI  - Dual-polarity GRAPPA for simultaneous reconstruction and ghost correction of echo
      planar imaging data.
AB  - PURPOSE: The purpose of this study was to seek improved image quality from
      accelerated echo planar imaging (EPI) data, particularly at ultrahigh fields.
      Certain artifacts in EPI reconstructions can be attributed to nonlinear phase
      differences between data acquired using frequency-encoding gradients of
      alternating polarity. These errors appear near regions of local susceptibility
      gradients and typically cannot be corrected with conventional Nyquist ghost
      correction (NGC) methods. METHODS: We propose a new reconstruction method that
      integrates ghost correction into the parallel imaging data recovery process. This
      is achieved through a pair of generalized autocalibrating partially parallel
      acquisitions (GRAPPA) kernels that operate directly on the measured EPI data. The
      proposed dual-polarity GRAPPA (DPG) method estimates missing k-space data while
      simultaneously correcting inherent EPI phase errors. RESULTS: Simulation results
      showed that standard NGC is incapable of correcting higher-order phase errors,
      whereas the DPG kernel approach successfully removed these errors. The presence
      of higher-order phase errors near regions of local susceptibility gradients was
      demonstrated with in vivo data. DPG reconstructions of in vivo 3T and 7T EPI data
      acquired near these regions showed a marked improvement over conventional
      methods. CONCLUSION: This new parallel imaging method for reconstructing
      accelerated EPI data shows better resilience to inherent EPI phase errors,
      resulting in higher image quality in regions where higher-order EPI phase errors
      commonly occur. Magn Reson Med 76:32-44, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26208306
TI  - A Cross-Modality Learning Approach for Vessel Segmentation in Retinal Images.
AB  - This paper presents a new supervised method for vessel segmentation in retinal
      images. This method remolds the task of segmentation as a problem of cross
      modality data transformation from retinal image to vessel map. A wide and deep
      neural network with strong induction ability is proposed to model the
      transformation, and an efficient training strategy is presented. Instead of a
      single label of the center pixel, the network can output the label map of all
      pixels for a given image patch. Our approach outperforms reported state-of-the
      art methods in terms of sensitivity, specificity and accuracy. The result of
      cross-training evaluation indicates its robustness to the training set. The
      approach needs no artificially designed feature and no preprocessing step,
      reducing the impact of subjective factors. The proposed method has the potential
      for application in image diagnosis of ophthalmologic diseases, and it may provide
      a new, general, high-performance computing framework for image segmentation. 

PMID- 26208305
TI  - Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of
      Treatment Outcome and Predictors of Response.
AB  - BACKGROUND: Deep brain stimulation (DBS) has been proposed as an alternative to
      ablative neurosurgery for severe treatment-resistant Obsessive-Compulsive
      Disorder (OCD), although with partially discrepant results probably related to
      differences in anatomical targetting and stimulation conditions. We sought to
      determine the efficacy and tolerability of DBS in OCD and the existence of
      clinical predictors of response using meta-analysis. METHODS: We searched the
      literature on DBS for OCD from 1999 through January 2014 using PubMed/MEDLINE and
      PsycINFO. We performed fixed and random-effect meta-analysis with score changes
      (pre-post DBS) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as the
      primary-outcome measure, and the number of responders to treatment, quality of
      life and acceptability as secondary measures. FINDINGS: Thirty-one studies
      involving 116 subjects were identified. Eighty-three subjects were implanted in
      striatal areas--anterior limb of the internal capsule, ventral capsule and
      ventral striatum, nucleus accumbens and ventral caudate--27 in the subthalamic
      nucleus and six in the inferior thalamic peduncle. Global percentage of Y-BOCS
      reduction was estimated at 45.1% and global percentage of responders at 60.0%.
      Better response was associated with older age at OCD onset and presence of
      sexual/religious obsessions and compulsions. No significant differences were
      detected in efficacy between targets. Five patients dropped out, but adverse
      effects were generally reported as mild, transient and reversible. CONCLUSIONS:
      Our analysis confirms that DBS constitutes a valid alternative to lesional
      surgery for severe, therapy-refractory OCD patients. Well-controlled, randomized
      studies with larger samples are needed to establish the optimal targeting and
      stimulation conditions and to extend the analysis of clinical predictors of
      outcome.

PMID- 26208308
TI  - Digital Tomosynthesis System Geometry Analysis Using Convolution-Based Blur-and
      Add (BAA) Model.
AB  - Digital tomosynthesis is a three-dimensional imaging technique with a lower
      radiation dose than computed tomography (CT). Due to the missing data in
      tomosynthesis systems, out-of-plane structures in the depth direction cannot be
      completely removed by the reconstruction algorithms. In this work, we analyzed
      the impulse responses of common tomosynthesis systems on a plane-to-plane basis
      and proposed a fast and accurate convolution-based blur-and-add (BAA) model to
      simulate the backprojected images. In addition, the analysis formalism describing
      the impulse response of out-of-plane structures can be generalized to both
      rotating and parallel gantries. We implemented a ray tracing forward projection
      and backprojection (ray-based model) algorithm and the convolution-based BAA
      model to simulate the shift-and-add (backproject) tomosynthesis reconstructions.
      The convolution-based BAA model with proper geometry distortion correction
      provides reasonably accurate estimates of the tomosynthesis reconstruction. A
      numerical comparison indicates that the simulated images using the two models
      differ by less than 6% in terms of the root-mean-squared error. This convolution
      based BAA model can be used in efficient system geometry analysis, reconstruction
      algorithm design, out-of-plane artifacts suppression, and CT-tomosynthesis
      registration. 

PMID- 26208307
TI  - Stacked Sparse Autoencoder (SSAE) for Nuclei Detection on Breast Cancer
      Histopathology Images.
AB  - Automated nuclear detection is a critical step for a number of computer assisted
      pathology related image analysis algorithms such as for automated grading of
      breast cancer tissue specimens. The Nottingham Histologic Score system is highly
      correlated with the shape and appearance of breast cancer nuclei in
      histopathological images. However, automated nucleus detection is complicated by
      1) the large number of nuclei and the size of high resolution digitized pathology
      images, and 2) the variability in size, shape, appearance, and texture of the
      individual nuclei. Recently there has been interest in the application of "Deep
      Learning" strategies for classification and analysis of big image data.
      Histopathology, given its size and complexity, represents an excellent use case
      for application of deep learning strategies. In this paper, a Stacked Sparse
      Autoencoder (SSAE), an instance of a deep learning strategy, is presented for
      efficient nuclei detection on high-resolution histopathological images of breast
      cancer. The SSAE learns high-level features from just pixel intensities alone in
      order to identify distinguishing features of nuclei. A sliding window operation
      is applied to each image in order to represent image patches via high-level
      features obtained via the auto-encoder, which are then subsequently fed to a
      classifier which categorizes each image patch as nuclear or non-nuclear. Across a
      cohort of 500 histopathological images (2200 * 2200) and approximately 3500
      manually segmented individual nuclei serving as the groundtruth, SSAE was shown
      to have an improved F-measure 84.49% and an average area under Precision-Recall
      curve (AveP) 78.83%. The SSAE approach also out-performed nine other state of the
      art nuclear detection strategies. 

PMID- 26208309
TI  - Robustness-Driven Feature Selection in Classification of Fibrotic Interstitial
      Lung Disease Patterns in Computed Tomography Using 3D Texture Features.
AB  - Lack of classifier robustness is a barrier to widespread adoption of computer
      aided diagnosis systems for computed tomography (CT). We propose a novel
      Robustness-Driven Feature Selection (RDFS) algorithm that preferentially selects
      features robust to variations in CT technical factors. We evaluated RDFS in CT
      classification of fibrotic interstitial lung disease using 3D texture features.
      CTs were collected for 99 adult subjects separated into three datasets: training,
      multi-reconstruction, testing. Two thoracic radiologists provided cubic volumes
      of interest corresponding to six classes: pulmonary fibrosis, ground-glass
      opacity, honeycombing, normal lung parenchyma, airway, vessel. The multi
      reconstruction dataset consisted of CT raw sinogram data reconstructed by
      systematically varying slice thickness, reconstruction kernel, and tube current
      (using a synthetic reduced-tube-current algorithm). Two support vector machine
      classifiers were created, one using RDFS ("with-RDFS") and one not ("without
      RDFS"). Classifier robustness was compared on the multi-reconstruction dataset,
      using Cohen's kappa to assess classification agreement against a reference
      reconstruction. Classifier performance was compared on the testing dataset using
      the extended g-mean (EGM) measure. With-RDFS exhibited superior robustness (kappa
      0.899-0.989) compared to without-RDFS (kappa 0.827-0.968). Both classifiers
      demonstrated similar performance on the testing dataset (EGM 0.778 for with-RDFS;
      0.785 for without-RDFS), indicating that RDFS does not compromise classifier
      performance when discarding nonrobust features. RDFS is highly effective at
      improving classifier robustness against slice thickness, reconstruction kernel,
      and tube current without sacrificing performance, a result that has implications
      for multicenter clinical trials that rely on accurate and reproducible
      quantitative analysis of CT images collected under varied conditions across
      multiple sites, scanners, and timepoints. 

PMID- 26208310
TI  - Augmented Likelihood Image Reconstruction.
AB  - The presence of high-density objects remains an open problem in medical CT
      imaging. Data of projections passing through objects of high density, such as
      metal implants, are dominated by noise and are highly affected by beam hardening
      and scatter. Reconstructed images become less diagnostically conclusive because
      of pronounced artifacts that manifest as dark and bright streaks. A new
      reconstruction algorithm is proposed with the aim to reduce these artifacts by
      incorporating information about shape and known attenuation coefficients of a
      metal implant. Image reconstruction is considered as a variational optimization
      problem. The afore-mentioned prior knowledge is introduced in terms of equality
      constraints. An augmented Lagrangian approach is adapted in order to minimize the
      associated log-likelihood function for transmission CT. During iterations,
      temporally appearing artifacts are reduced with a bilateral filter and new
      projection values are calculated, which are used later on for the reconstruction.
      A detailed evaluation in cooperation with radiologists is performed on software
      and hardware phantoms, as well as on clinically relevant patient data of subjects
      with various metal implants. Results show that the proposed reconstruction
      algorithm is able to outperform contemporary metal artifact reduction methods
      such as normalized metal artifact reduction. 

PMID- 26208312
TI  - Reduced graphene oxide anchored Cu(OH)2 as a high performance electrochemical
      supercapacitor.
AB  - Developing new materials for electrochemical supercapacitors with higher energy
      density has recently gained tremendous impetus in the context of effective
      utilization of renewable energy. Herein, we report a simple one-pot synthesis of
      bundled nanorods of Cu(OH)2 embedded in a matrix of reduced graphene oxide
      (Cu(OH)2@RGO) under mild hydrothermal conditions of 80  degrees C for 1 h. The
      synthesized material shows a high BET surface area of 78.7 m(2) g(-1) and a
      mesoporous nature with a broad pore-size distribution consisting of structural
      pores as well as inter-particle pores. Raman spectroscopy suggests an intimate
      interaction between Cu(OH)2 and reduced graphene oxide (RGO) creating more
      defects by destruction of sp(2) domains which would help the defect-assisted
      charge transport during electrochemical processes. When investigated as an
      electrochemical supercapacitor, Cu(OH)2@RGO shows a high capacitance of 602 F g(
      1) at 0.2 A g(-1) in 1 M KOH in a three-electrode cell configuration. Detailed
      electrochemical studies indicate that the Faradic processes are diffusion
      controlled and follow a quasi-reversible kinetics. Further, a two-electrode
      symmetric cell shows good energy density and power density (84.5 Wh kg(-1) at
      0.55 kW kg(-1) and 20.5 Wh kg(-1) at 5.5 kW kg(-1)) characteristics demonstrating
      superior application potential of this common low-cost transition metal hydroxide
      for high performance energy storage devices. 

PMID- 26208311
TI  - High Total Cholesterol in Peripheral Blood Correlates with Poorer Hearing
      Recovery in Idiopathic Sudden Sensorineural Hearing Loss.
AB  - Idiopathic sudden sensorineural hearing loss (ISSHL) is a common otologic
      emergency whose cause is still unclear. The importance of blood lipids in the
      pathogenesis of ISSHL is widely reported in literature. In fact elevated levels
      of low density lipoprotein cholesterol (LDL), total cholesterol (TC) and
      apolipoprotein B (Apo-B) have been proposed as risk factors for this pathology.
      No correlation has been described between serum lipid parameters and the
      prognosis of ISSHL. Aim of the present study was to identify prognostic factors
      associated with hearing recovery in a group of patients affected by ISSHL. Ninety
      four patients with the diagnosis of ISSHL hospitalized between March 2013 and
      October 2014 were included in this study. Patients' blood sampling and hearing
      assessments were carried out. Patients were divided into two groups as
      "recovered" and "unrecovered", according to their response to the treatment. We
      found a statistically significant higher level of total cholesterol in the
      unrecovered group compared to the recovered one (p = 0.03). None of the other
      routine laboratory parameters have shown a statistically significant difference
      between the patients successfully treated and patients with poor outcomes. Total
      cholesterol concentrations may be a prognostic factor for recovery in ISSHL and
      should be assessed together with routine tests in patients with this condition.
      The other routine laboratory parameters seem to have no effect on the development
      and prognosis of this pathology. 

PMID- 26208313
TI  - Genome-wide high-throughput SNP discovery and genotyping for understanding
      natural (functional) allelic diversity and domestication patterns in wild
      chickpea.
AB  - We identified 82489 high-quality genome-wide SNPs from 93 wild and cultivated
      Cicer accessions through integrated reference genome- and de novo-based GBS
      assays. High intra- and inter-specific polymorphic potential (66-85%) and broader
      natural allelic diversity (6-64%) detected by genome-wide SNPs among accessions
      signify their efficacy for monitoring introgression and transferring target trait
      regulating genomic (gene) regions/allelic variants from wild to cultivated Cicer
      gene pools for genetic improvement. The population-specific assignment of wild
      Cicer accessions pertaining to the primary gene pool are more influenced by
      geographical origin/phenotypic characteristics than species/gene-pools of
      origination. The functional significance of allelic variants (non-synonymous and
      regulatory SNPs) scanned from transcription factors and stress-responsive genes
      in differentiating wild accessions (with potential known sources of yield
      contributing and stress tolerance traits) from cultivated desi and kabuli
      accessions, fine-mapping/map-based cloning of QTLs and determination of LD
      patterns across wild and cultivated gene-pools are suitably elucidated. The
      correlation between phenotypic (agromorphological traits) and molecular diversity
      based admixed domestication patterns within six structured populations of wild
      and cultivated accessions via genome-wide SNPs was apparent. This suggests
      utility of whole genome SNPs as a potential resource for identifying naturally
      selected trait-regulating genomic targets/functional allelic variants adaptive to
      diverse agroclimatic regions for genetic enhancement of cultivated gene-pools. 

PMID- 26208314
TI  - Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers
      of Peritoneal Metastasis in Gastric Cancer.
AB  - Peritoneal metastasis is the most frequent type of recurrence in patients with
      gastric cancer (GC) and is associated with poor prognosis. Peritoneal lavage
      cytology, used to evaluate the risk of peritoneal metastasis, has low
      sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA
      profiles in peritoneal fluid for the prediction of peritoneal dissemination in
      GC. Total RNA was extracted from exosomes isolated from six gastric malignant
      ascites (MA) samples, 24 peritoneal lavage fluid (PLF) samples, and culture
      supernatants (CM) of two human gastric carcinoma cell lines that differ in their
      potential for peritoneal metastasis. Expression of exosomal miRNAs was evaluated
      with Agilent Human miRNA microarrays and quantitative reverse transcription
      polymerase chain reaction (qRT-PCR). The microarray analysis indicated a low
      variability in the number and signal intensity of miRNAs detected among the
      samples. In the six MA fluids, miR-21 showed the highest signal intensity. We
      identified five miRNAs (miR-1225-5p, miR-320c, miR-1202, miR-1207-5p, and miR
      4270) with high expression in MA samples, the PLF of serosa-invasive GC, and the
      CM of a highly metastatic GC cell line; these candidate miRNA species appear to
      be related to peritoneal dissemination. Differential expression of miR-21, miR
      320c, and miR-1225-5p was validated in the PLF of serosa-invasive and non
      invasive GC by qRT-PCR and miR-21 and miR-1225-5p were confirmed to be associated
      with serosal invasion in GC. PLF can be used to profile the expression of
      exosomal miRNAs. Our findings suggest that miR-21 and miR-1225-5p may serve as
      biomarkers of peritoneal recurrence after curative GC resection, thus providing a
      novel approach to early diagnosis of peritoneal dissemination of GC. 

PMID- 26208315
TI  - Application of Individualized Speed Thresholds to Interpret Position Specific
      Running Demands in Elite Professional Rugby Union: A GPS Study.
AB  - A number of studies have used GPS technology to categorise rugby union locomotive
      demands. However, the utility of the results of these studies is confounded by
      small sample sizes, sub-elite player status and the global application of
      absolute speed thresholds to all player positions. Furthermore, many of these
      studies have used GPS units with low sampling frequencies. The aim of the present
      study was to compare and contrast the high speed running (HSR) demands of
      professional rugby union when utilizing micro-technology units sampling at 10 Hz
      and applying relative or individualised speed zones. The results of this study
      indicate that application of individualised speed zones results in a significant
      shift in the interpretation of the HSR demands of both forwards and backs and
      positional sub-categories therein. When considering the use of an absolute in
      comparison to an individualised HSR threshold, there was a significant
      underestimation for forwards of HSR distance (HSRD) (absolute = 269 +/- 172.02,
      individualised = 354.72 +/- 99.22, p < 0.001), HSR% (absolute = 5.15 +/- 3.18,
      individualised = 7.06 +/- 2.48, p < 0.001) and HSR efforts (HSRE) (absolute =
      18.81 +/- 12.25; individualised = 24.78 +/- 8.30, p < 0.001). In contrast, there
      was a significant overestimation of the same HSR metrics for backs with the use
      of an absolute threshold (HSRD absolute = 697.79 +/- 198.11, individualised =
      570.02 +/- 171.14, p < 0.001; HSR% absolute = 10.85 +/- 2.82, individualised =
      8.95 +/- 2.76, p < 0.001; HSRE absolute = 41.55 +/- 11.25; individualised = 34.54
      +/- 9.24, p < 0.001). This under- or overestimation associated with an absolute
      speed zone applies to varying degrees across the ten positional sub-categories
      analyzed and also to individuals within the same positional sub-category. The
      results of the present study indicated that although use of an individulised HSR
      threshold improves the interpretation of the HSR demands on a positional basis,
      inter-individual variability in maximum velocity within positional sub-categories
      means that players need to be considered on an individual basis to accurately
      gauge the HSR demands of rugby union. 

PMID- 26208316
TI  - Combining plasma measurements and mechanistic modeling to explore the effect of
      POPs on type 2 diabetes mellitus in Norwegian women.
AB  - The number of studies on persistent organic pollutants (POPs) and type 2 diabetes
      mellitus (T2DM) is growing steadily. Although concentrations of many POPs in
      humans have decreased substantially, only some studies consider temporal and
      inter-individual changes in POP concentrations when assessing exposure. Here we
      combined plasma measurements with mechanistic modeling to generate complementary
      exposure measures to our single blood draw after disease diagnosis. Blood was
      collected between 2003-2006 from 106 subjects with T2DM and 106 age-matched
      controls, and POP concentrations were compared after adjustment for relevant risk
      factors and multiple testing. Area under the curve (AUC) of PCB-153 from birth
      until age 18, representing early-life exposure, and AUC from birth until time of
      diagnosis were generated as well as examples of life-time exposure trajectories
      using a mechanistic exposure model. The rank sum of polychlorinated biphenyls
      (PCBs) and organochlorine pesticides (OCPs, OR=16.9 (95% CI: 3.05-93.6)) as well
      as beta-hexachlorocyclohexane (beta-HCH, OR=203.8 (95% CI: 11.5-3620)) and 1, 1
      dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE, OR=11.3 (95% CI: 2.55-49.9))
      were associated with T2DM. Neither of the AUCs reflecting early life exposure and
      total life-time exposure at the time of diagnosis were associated with the
      disease. The predicted life course trajectories display clear differences within
      and between individuals in the past and suggest that a single blood draw provide
      limited information on POP exposure earlier in life. The predicted AUCs for PCB
      153 did not support the positive association between T2DM and measured blood
      concentration of certain POPs. This may suggest that the model is either too
      simplistic and/or that strength of the association may vary through life and with
      time to/past diagnosis. 

PMID- 26208317
TI  - Enhanced growth suppression of TERT-positive tumor cells by oncolytic adenovirus
      armed with CCL20 and CD40L.
AB  - Conditionally replicating adenoviruses (CRAds) selectively replicate in cancer
      cells and induce cell lysis, which represents a potential platform for cancer
      immunotherapy. The chemokine CCL20 exerts antitumor activity via chemoattraction
      of immature dendritic cells (DCs) and lymphocytes. However, the activation and
      maturation status of DCs is a limiting factor in the DCs -based immunity
      response. CD40L induces the phenotypic maturation of DCs, mediates DCs cytokine
      secretion, and increases the expression of FasL, which mediates apoptosis. We
      constructed a CCL20/CD40L co-expression CRAds (Ad-CCL20-CD40L) based on the
      AdEasy system. Ad-CCL20-CD40L was constructed from three plasmids, pGTE-CD40L,
      pShuttle-CMV-CCL20 and AdEasy-1, and was homologously recombined and propagated
      in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293,
      respectively. Ad-CCL20-CD40L selectively replicates in TERT-positive tumor cells
      because the pGTE-CD40L plasmid contains the telomerase reverse transcriptase
      promoter (TERTp). Our results showed that Ad-CCL20-CD40L induced oncolytic
      effects and tumor-specific cytotoxicity of cytotoxic T lymphocytes (CTLs) in
      vitro. This study suggests that Ad-CCL20-CD40L can induce the antitumor immune
      response and that this platform can be modified to generate novel CRAds with
      other transgenes. 

PMID- 26208318
TI  - Cancer death rates in US congressional districts.
AB  - Knowledge of the cancer burden is important for informing and advocating cancer
      prevention and control. Mortality data are readily available for states and
      counties, but not for congressional districts, from which representatives are
      elected and which may be more influential in compelling legislation and policy.
      The authors calculated average annual cancer death rates during 2002 to 2011 for
      each of the 435 congressional districts using mortality data from the National
      Center for Health Statistics and population estimates from the US Census Bureau.
      Age-standardized death rates were mapped for all sites combined and separately
      for cancers of the lung and bronchus, colorectum, breast, and prostate by
      race/ethnicity and sex. Overall cancer death rates vary by almost 2-fold and are
      generally lowest in Mountain states and highest in Appalachia and areas of the
      South. The distribution is similar for lung and colorectal cancers, with the
      lowest rates consistently noted in districts in Utah. However, for breast and
      prostate cancers, while the highest rates are again scattered throughout the
      South, the geographic pattern is less clear and the lowest rates are in Hawaii
      and southern Texas and Florida. Within-state heterogeneity is limited,
      particularly for men, with the exceptions of Texas, Georgia, and Florida.
      Patterns also vary by race/ethnicity. For example, the highest prostate cancer
      death rates are in the West and north central United States among non-Hispanic
      whites, but in the deep South among African Americans. Hispanics have the lowest
      rates except for colorectal cancer in Wyoming, eastern Colorado, and northern New
      Mexico. These data can facilitate cancer control and stimulate conversation about
      the relationship between cancer and policies that influence access to health care
      and the prevalence of behavioral and environmental risk factors.

PMID- 26208320
TI  - In vivo second-harmonic generation and ex vivo coherent anti-stokes raman
      scattering microscopy to study the effect of obesity to fibroblast cell function
      using an Yb-fiber laser-based CARS extension unit.
AB  - Nonlinear microscopy techniques are being increasingly used to perform in vivo
      studies in dermatology. These methods enable us to investigate the morphology and
      monitor the physiological process in the skin by the use of femtosecond lasers
      operating in the red, near-infrared spectral range (680-1,300 nm). In this work
      we used two different techniques that require no labeling: second harmonic
      generation (SHG) for collagen detection and coherent anti-Stokes Raman scattering
      (CARS) to assess lipid distribution in genetically obese murine skin. Obesity is
      one of the most serious public health problems due to its high and increasing
      prevalence and the associated risk of type 2 diabetes and cardiovascular
      diseases. Other than these diseases, nearly half of patients with diabetes
      mellitus suffer from dermatological complications such as delayed wound healing,
      foot ulcers and several other skin changes. In our experiment we investigated and
      followed the effects of obesity on dermal collagen alterations and adipocyte
      enlargement using a technique not reported in the literature so far. Our results
      indicate that the in vivo SHG and ex vivo CARS imaging technique might be an
      important tool for diagnosis of diabetes-related skin disorders in the near
      future.

PMID- 26208321
TI  - Problems in the fingerprints based polycyclic aromatic hydrocarbons source
      apportionment analysis and a practical solution.
AB  - This work intended to explain the challenges of the fingerprints based source
      apportionment method for polycyclic aromatic hydrocarbons (PAH) in the aquatic
      environment, and to illustrate a practical and robust solution. The PAH data
      detected in the sediment cores from the Illinois River provide the basis of this
      study. Principal component analysis (PCA) separates PAH compounds into two groups
      reflecting their possible airborne transport patterns; but it is not able to
      suggest specific sources. Not all positive matrix factorization (PMF) determined
      sources are distinguishable due to the variability of source fingerprints.
      However, they constitute useful suggestions for inputs for a Bayesian chemical
      mass balance (CMB) analysis. The Bayesian CMB analysis takes into account the
      measurement errors as well as the variations of source fingerprints, and provides
      a credible source apportionment. Major PAH sources for Illinois River sediments
      are traffic (35%), coke oven (24%), coal combustion (18%), and wood combustion
      (14%). 

PMID- 26208319
TI  - The C. elegans Chp/Wrch Ortholog CHW-1 Contributes to LIN-18/Ryk and LIN
      17/Frizzled Signaling in Cell Polarity.
AB  - Wnt signaling controls various aspects of developmental and cell biology, as well
      as contributing to certain cancers. Expression of the human Rho family small
      GTPase Wrch/RhoU is regulated by Wnt signaling, and Wrch and its paralog Chp/RhoV
      are both implicated in oncogenic transformation and regulation of cytoskeletal
      dynamics. We performed developmental genetic analysis of the single
      Caenorhabditis elegans ortholog of Chp and Wrch, CHW-1. Using a transgenic assay
      of the distal tip cell migration, we found that wild-type CHW-1 is likely to be
      partially constitutively active and that we can alter ectopic CHW-1-dependent
      migration phenotypes with mutations predicted to increase or decrease intrinsic
      GTP hydrolysis rate. The vulval P7.p polarity decision balances multiple
      antagonistic Wnt signals, and also uses different types of Wnt signaling.
      Previously described cooperative Wnt receptors LIN-17/Frizzled and LIN-18/Ryk
      orient P7.p posteriorly, with LIN-17/Fz contributing approximately two-thirds of
      polarizing activity. CHW-1 deletion appears to equalize the contributions of
      these two receptors. We hypothesize that CHW-1 increases LIN-17/Fz activity at
      the expense of LIN-18/Ryk, thus making the contribution of these signals unequal.
      For P7.p to polarize correctly and form a proper vulva, LIN-17/Fz and LIN-18/Ryk
      antagonize other Wnt transmembrane systems VANG-1/VanGogh and CAM-1/Ror. Our
      genetic data suggest that LIN-17/Fz represses both VANG-1/VanGogh and CAM-1/Ror,
      while LIN-18/Ryk represses only VANG-1. These data expand our knowledge of a
      sophisticated signaling network to control P7.p polarity, and suggests that CHW-1
      can alter ligand gradients or receptor priorities in the system. 

PMID- 26208322
TI  - Has the Reform of the Japanese Healthcare Provision System Improved the Value in
      Healthcare? A Cost-Consequence Analysis of Organized Care for Hip Fracture
      Patients.
AB  - OBJECTIVES: To assess the value of organized care by comparing the clinical
      outcomes and healthcare expenditure between the conventional Japanese "integrated
      care across specialties within one hospital" mode of providing healthcare and the
      prospective approach of "organized care across separate facilities within a
      community". DESIGN: Retrospective cohort study. SETTING: Two groups of hospitals
      were categorized according to healthcare delivery approach: the first group
      included 3 hospitals autonomously providing integrated care across specialties,
      and the second group included 4 acute care hospitals and 7 rehabilitative care
      hospitals providing organized care across separate facilities. PARTICIPANTS:
      Patients aged 65 years and above who had undergone hip fracture surgery.
      MEASUREMENTS: Regression models adjusting for patient characteristics and
      clinical variables were used to investigate the impact of organized care on the
      improvements to the mobility capability of patients before and after
      hospitalization and the differences in healthcare resource utilization. RESULTS:
      The sample for analysis included 837 hip fracture surgery cases. The proportion
      of patients with either unchanged or improved mobility capability was not
      statistically associated with the healthcare delivery approaches. Total adjusted
      mean healthcare expenditure for integrated care and organized care were US$28,360
      (95% confidence interval: 27,787-28,972) and US$21,951 (21,511-22,420),
      respectively, indicating an average increase of US$6,409 in organized care.
      CONCLUSION: Our cost-consequence analysis underscores the need to further
      investigate the actual contribution of organized care to the provision of
      efficient and high-quality healthcare.

PMID- 26208323
TI  - Improved Methods to Generate Spheroid Cultures from Tumor Cells, Tumor Cells &
      Fibroblasts or Tumor-Fragments: Microenvironment, Microvesicles and MiRNA.
AB  - Diagnostic and prognostic indicators are key components to achieve the goal of
      personalized cancer therapy. Two distinct approaches to this goal include
      predicting response by genetic analysis and direct testing of possible therapies
      using cultures derived from biopsy specimens. Optimally, the latter method
      requires a rapid assessment, but growing xenograft tumors or developing patient
      derived cell lines can involve a great deal of time and expense. Furthermore,
      tumor cells have much different responses when grown in 2D versus 3D tissue
      environments. Using a modification of existing methods, we show that it is
      possible to make tumor-fragment (TF) spheroids in only 2-3 days. TF spheroids
      appear to closely model characteristics of the original tumor and may be used to
      assess critical therapy-modulating features of the microenvironment such as
      hypoxia. A similar method allows the reproducible development of spheroids from
      mixed tumor cells and fibroblasts (mixed-cell spheroids). Prior literature
      reports have shown highly variable development and properties of mixed-cell
      spheroids and this has hampered the detailed study of how individual tumor-cell
      components interact. In this study, we illustrate this approach and describe
      similarities and differences using two tumor models (U87 glioma and SQ20B
      squamous-cell carcinoma) with supporting data from additional cell lines. We show
      that U87 and SQ20B spheroids predict a key microenvironmental factor in tumors
      (hypoxia) and that SQ20B cells and spheroids generate similar numbers of
      microvesicles. We also present pilot data for miRNA expression under conditions
      of cells, tumors, and TF spheroids. 

PMID- 26208324
TI  - Correction: Genetic Affinity of the Bhil, Kol and Gond Mentioned in Epic
      Ramayana.

PMID- 26208325
TI  - Comprehensive Molecular Analysis of NSCLC; Clinicopathological Associations.
AB  - BACKGROUND: Selection of NSCLC patients for targeted therapy is currently based
      upon the presence of sensitizing mutations in EGFR and EML4/ALK translocations.
      The heterogeneity of molecular alterations in lung cancer has led to the ongoing
      discovery of potential biomarkers and targets in order to improve survival. AIM:
      This study aimed to detect alterations in EGFR, KRAS, BRAF, PIK3CA, MET-gene copy
      number and ALK rearrangements in a large cohort of 956 NSCLC patients of Hellenic
      origin using highly sensitive techniques and correlations with
      clinicopathological characteristics. RESULTS: Mutations were detected in EGFR
      10.6% (101 out of 956 samples), KRAS 26.5% (191 out of 720 samples), BRAF 2.5%
      (12 out of 471 samples), PIK3CA 3.8% (7 out of 184 samples), MET gene
      amplification was detected in 18% (31 out of 170) and ALK rearrangements in 3.7%
      (4 out of 107 samples). EGFR mutations were detected in exon 19 (61.4% of mutant
      cases), exon 21 p.Leu858Arg (19.8%), exon 20 (15.8%), exon 18 (2.9%) and were
      correlated with gender histology, smoking status and TTF1 staining. p.Thr790Met
      mutant cases (3.9%) displayed concurrent mutations in exons 19 or 21. Negative
      TTF-1 staining showed strong negative predictive value for the presence of EGFR
      mutations. KRAS mutations were associated with histology, the most common
      mutation being p.Gly12Cys (38%). DISCUSSION: In conclusion, only 89 patients were
      eligible for EGFR -TKIs and ALK inhibitors therapy, whereas 257 patients showed
      other alterations, highlighting the necessity for a detailed molecular profiling
      potentially leading to more efficient individualized therapies for NSCLC
      patients.

PMID- 26208326
TI  - N-Terminal Coiled-Coil Structure of ATPase Subunits of 26S Proteasome Is Crucial
      for Proteasome Function.
AB  - The proteasome is an essential proteolytic machine in eukaryotic cells, where it
      removes damaged proteins and regulates many cellular activities by degrading
      ubiquitinated proteins. Its heterohexameric AAA+ ATPase Rpt subunits play a
      central role in proteasome activity by the engagement of substrate unfolding and
      translocation for degradation; however, its detailed mechanism remains poorly
      understood. In contrast to AAA+ ATPase domains, their N-terminal regions of Rpt
      subunits substantially differ from each other. Here, to investigate the
      requirements and roles of the N-terminal regions of six Rpt subunits derived from
      Saccharomyces cerevisiae, we performed systematic mutational analysis using
      conditional knockdown yeast strains for each Rpt subunit and bacterial
      heterologous expression system of the base subcomplex. We showed that the
      formation of the coiled-coil structure was the most important for the N-terminal
      region of Rpt subunits. The primary role of coiled-coil structure would be the
      maintenance of the ring structure with the defined order. However, the coiled
      coil region would be also be involved in substrate recognition and an interaction
      between lid and base subcomplexes. 

PMID- 26208327
TI  - Evaluation of Cross-Protocol Stability of a Fully Automated Brain Multi-Atlas
      Parcellation Tool.
AB  - Brain parcellation tools based on multiple-atlas algorithms have recently emerged
      as a promising method with which to accurately define brain structures. When
      dealing with data from various sources, it is crucial that these tools are robust
      for many different imaging protocols. In this study, we tested the robustness of
      a multiple-atlas, likelihood fusion algorithm using Alzheimer's Disease
      Neuroimaging Initiative (ADNI) data with six different protocols, comprising
      three manufacturers and two magnetic field strengths. The entire brain was
      parceled into five different levels of granularity. In each level, which defines
      a set of brain structures, ranging from eight to 286 regions, we evaluated the
      variability of brain volumes related to the protocol, age, and diagnosis (healthy
      or Alzheimer's disease). Our results indicated that, with proper pre-processing
      steps, the impact of different protocols is minor compared to biological effects,
      such as age and pathology. A precise knowledge of the sources of data variation
      enables sufficient statistical power and ensures the reliability of an anatomical
      analysis when using this automated brain parcellation tool on datasets from
      various imaging protocols, such as clinical databases. 

PMID- 26208328
TI  - Broad-Band Visually Evoked Potentials: Re(con)volution in Brain-Computer
      Interfacing.
AB  - Brain-Computer Interfaces (BCIs) allow users to control devices and communicate
      by using brain activity only. BCIs based on broad-band visual stimulation can
      outperform BCIs using other stimulation paradigms. Visual stimulation with pseudo
      random bit-sequences evokes specific Broad-Band Visually Evoked Potentials
      (BBVEPs) that can be reliably used in BCI for high-speed communication in speller
      applications. In this study, we report a novel paradigm for a BBVEP-based BCI
      that utilizes a generative framework to predict responses to broad-band
      stimulation sequences. In this study we designed a BBVEP-based BCI using
      modulated Gold codes to mark cells in a visual speller BCI. We defined a linear
      generative model that decomposes full responses into overlapping single-flash
      responses. These single-flash responses are used to predict responses to novel
      stimulation sequences, which in turn serve as templates for classification. The
      linear generative model explains on average 50% and up to 66% of the variance of
      responses to both seen and unseen sequences. In an online experiment, 12
      participants tested a 6 * 6 matrix speller BCI. On average, an online accuracy of
      86% was reached with trial lengths of 3.21 seconds. This corresponds to an
      Information Transfer Rate of 48 bits per minute (approximately 9 symbols per
      minute). This study indicates the potential to model and predict responses to
      broad-band stimulation. These predicted responses are proven to be well-suited as
      templates for a BBVEP-based BCI, thereby enabling communication and control by
      brain activity only. 

PMID- 26208329
TI  - ICD Shock, Not Ventricular Fibrillation, Causes Elevation of High Sensitive
      Troponin T after Defibrillation Threshold Testing--The Prospective, Randomized,
      Multicentre TropShock-Trial.
AB  - BACKGROUND: The placement of an implantable cardioverter defibrillator (ICD) has
      become routine practice to protect high risk patients from sudden cardiac death.
      However, implantation-related myocardial micro-damage and its relation to
      different implantation strategies are poorly characterized. METHODS: A total of
      194 ICD recipients (64+/-12 years, 83% male, 95% primary prevention of sudden
      cardiac death, 35% cardiac resynchronization therapy) were randomly assigned to
      one of three implantation strategies: (1) ICD implantation without any
      defibrillation threshold (DFT) testing, (2) estimation of the DFT without
      arrhythmia induction (modified "upper limit of vulnerability (ULV) testing") or
      (3) traditional safety margin testing including ventricular arrhythmia induction.
      High-sensitive Troponin T (hsTnT) levels were determined prior to the
      implantation and 6 hours after. RESULTS: All three groups showed a postoperative
      increase of hsTnT. The mean delta was 0.031+/-0.032 ng/ml for patients without
      DFT testing, 0.080+/-0.067 ng/ml for the modified ULV-testing and 0.064+/-0.056
      ng/ml for patients with traditional safety margin testing. Delta hsTnT was
      significantly larger in both of the groups with intraoperative ICD testing
      compared to the non-testing strategy (p<=0.001 each). There was no statistical
      difference in delta hsTnT between the two groups with intraoperative ICD testing
      (p = 0.179). CONCLUSION: High-sensitive Troponin T release during ICD
      implantation is significantly higher in patients with intraoperative ICD testing
      using shock applications compared to those without testing. Shock applications,
      with or without arrhythmia induction, did not result in a significantly different
      delta hsTnT. Hence, the ICD shock itself and not ventricular fibrillation seems
      to cause myocardial micro-damage. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01230086.

PMID- 26208330
TI  - DNA-mediated supercharged fluorescent protein/graphene oxide interaction for
      label-free fluorescence assay of base excision repair enzyme activity.
AB  - The interaction between supercharged green fluorescent protein (ScGFP) and
      graphene oxide (GO) as well as the resulting quenching effect of GO on ScGFP were
      investigated. Based on this unique quenching effect and the DNA-mediated ScGFP/GO
      interaction, a label-free fluorescence method has been established for
      homogeneously assaying the activity and inhibition of base excision repair
      enzyme. 

PMID- 26208332
TI  - Correction: Political Attitudes Develop Independently of Personality Traits.

PMID- 26208331
TI  - Association between the Adherence to the International Guidelines for Cancer
      Prevention and Mammographic Density.
AB  - INTRODUCTION: Mammographic density (MD) is considered a strong predictor of
      Breast Cancer (BC). The objective of the present study is to explore the
      association between MD and the compliance with the World Cancer Research Fund and
      the American Institute for Cancer Research (WCRF/AICR) recommendations for cancer
      prevention. METHODS: Data of 3584 women attending screening from a population
      based multicenter cross-sectional study (DDM-Spain) collected from October 7,
      2007 through July 14, 2008, was used to calculate a score that measures the level
      of compliance with the WCRF/AICR recommendations: R1)Maintain adequate body
      weight; R2)Be physically active; 3R)Limit the intake of high density foods;
      R4)Eat mostly plant foods; R5)Limit the intake of animal foods; R6)Limit alcohol
      intake; R7)Limit salt and salt preserved food intake; R8)Meet nutritional needs
      through diet. The association between the score and MD (assessed by a single
      radiologist using a semi-quantitative scale) was evaluated using ordinal logistic
      models with random center-specific intercepts adjusted for the main determinants
      of MD. Stratified analyses by menopausal status and smoking status were also
      carried out. RESULTS: A higher compliance with the WCRF/AICR recommendations was
      associated with lower MD (OR1-unit increase = 0.93 95%CI:0.86;0.99). The
      association was stronger in postmenopausal women (OR = 0.91 95%CI:0.84;0.99) and
      nonsmokers (OR = 0.87;95%CI:0.80;0.96 for nonsmokers, OR = 1.01 95%CI:0.91;1.12
      for smokers, P-interaction = 0.042). Among nonsmokers, maintaining adequate body
      weight (OR = 0.81 95%CI:0.65;1.01), practicing physical activity (OR = 0.68
      95%CI:0.48;0.96) and moderating the intake of high-density foods (OR = 0.58
      95%CI:0.40;0.86) and alcoholic beverages (OR = 0.76 95%CI:0.55;1.05) were the
      recommendations showing the strongest associations with MD. CONCLUSIONS:
      postmenopausal women and non-smokers with greater compliance with the WCRF/AICR
      guidelines have lower MD. These results may provide guidance to design specific
      recommendations for screening attendants with high MD and therefore at higher
      risk of developing BC.

PMID- 26208333
TI  - LPS-Stimulated Whole Blood Cytokine Production Is Not Related to Disease Behavior
      in Patients with Quiescent Crohn's Disease.
AB  - INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory disease in which
      cytokines play a pivotal role in the induction and maintenance of inflammation.
      Innate cytokine production is genetically determined and varies largely between
      individuals; this might impact the severity of inflammation. We aimed to assess
      whether ex-vivo endotoxin-stimulated levels of cytokines could be associated with
      disease phenotype. METHODS: Patients with quiescent CD (Harvey-Bradshaw Index <=
      4 and negative inflammation markers) who were not using immunomodulating drugs or
      biologicals were eligible. Historical disease characteristics (localization,
      behavior, number of bowel resections, drug history, extra-intestinal symptoms)
      were extracted from medical records. We measured cytokine levels (tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10) in supernatants of
      lipopolysaccharide (LPS) -stimulated whole blood cultures and correlated these
      with disease characteristics and age- and sex-matched healthy controls. In
      addition, we analyzed whether single nucleotide polymorphisms (SNPs) in the
      promoter region of the TNF-alpha gene were related to TNF-alpha levels. RESULTS:
      We included 75 patients with CD and 24 healthy controls. Six patients were
      excluded because of increased inflammation markers resulting in a total of 69
      patients. The mean age (SD) of patients with CD was 51.2 (12.3) years with a mean
      (SD) disease duration of 24.1 (11.5) years. Disease localization, peri-anal
      involvement and behavior were not related to LPS-stimulated TNF-alpha, IL-1beta,
      IL-6 or IL-10 levels. In addition, combination of localization with behavior to
      differentiate mild from severe disease type showed no significant differences.
      TNF-alpha levels were higher in patients with CD (428 pg/ml IQR [267-468])
      compared to healthy controls (459 pg/ml IQR [364-570], p=0.02). We found no
      associations between SNPs in the promoter region and TNF-alpha levels.
      CONCLUSION: In this study, innate cytokine production of TNF-alpha, IL-1beta, IL
      6 and IL-10 was not related to historical disease characteristics or disease
      severity in patients with quiescent CD. These findings suggest that genetically
      determined levels of these cytokines obtained from LPS-stimulated whole blood
      cultures are not linked with disease behavior or severity.

PMID- 26208334
TI  - Evaluation of a pharmacist-run antiarrhythmic clinic in an ambulatory practice.
AB  - OBJECTIVE: To describe the impact of a pharmacist-run antiarrhythmic clinic in an
      outpatient practice. SETTING: Blanchard Valley Medical Associates (BVMA) in
      Findlay, OH. PRACTICE DESCRIPTION: BVMA is a 15-physician private practice with
      five pharmacists on staff who run several disease management clinics. PRACTICE
      INNOVATION: Patients receiving amiodarone or sotalol are referred to a pharmacist
      run antiarrhythmic clinic within an outpatient physicians' office. The pharmacist
      is responsible for coordinating, monitoring, and reviewing results with patients.
      EVALUATION: A retrospective chart review was conducted to compare adherence to
      monitoring protocols between patients referred to the pharmacist-run clinic and
      patients managed solely by physicians, and to evaluate the type and frequency of
      pharmacist-initiated interventions. Patients had received antiarrhythmic
      treatment for at least 6 months before the beginning of the retrospective review.
      RESULTS: A total of 130 patient charts were reviewed. Adherence for each
      recommended testing parameter for patients on amiodarone and sotalol was
      significantly higher among patients managed by a pharmacist, compared with usual
      care. A total of 62 adverse events were detected, and 39 interventions were made
      by the pharmacist group. CONCLUSION: Patients with pharmacist monitoring of
      outpatient antiarrhythmic medications had greater adherence to recommended
      testing protocols compared with usual care.

PMID- 26208335
TI  - Finite element analysis for normal pressure hydrocephalus: The effects of the
      integration of sulci.
AB  - Finite element analysis (FEA) is increasingly used to investigate the brain under
      various pathological changes. Although FEA has been used to study hydrocephalus
      for decades, previous studies have primarily focused on ventriculomegaly. The
      present study aimed to investigate the pathologic changes regarding sulcal
      deformation in normal pressure hydrocephalus (NPH). Two finite element (FE)
      models-an anatomical brain geometric (ABG) model and the conventional simplified
      brain geometric (SBG) model-of NPH were constructed. The models were constructed
      with identical boundary conditions but with different geometries. The ABG model
      contained details of the sulci geometry, whereas these details were omitted from
      the SBG model. The resulting pathologic changes were assessed via four
      biomechanical parameters: pore pressure, von Mises stress, pressure, and void
      ratio. NPH was induced by increasing the transmantle pressure gradient (TPG) from
      0 to a maximum of 2.0 mmHg. Both models successfully simulated the major features
      of NPH (i.e., ventriculomegaly and periventricular lucency). The changes in the
      biomechanical parameters with increasing TPG were similar between the models.
      However, the SBG model underestimated the degree of stress across the cerebral
      mantle by 150% compared with the ABG model. The SBG model also overestimates the
      degree of ventriculomegaly (increases of 194.5% and 154.1% at TPG = 2.0 mmHg for
      the SBG and ABG models, respectively). Including the sulci geometry in a FEA for
      NPH clearly affects the overall results. The conventional SBG model is inferior
      to the ABG model, which accurately simulated sulcal deformation and the
      consequent effects on cortical or subcortical structures. The inclusion of sulci
      in future FEA for the brain is strongly advised, especially for models used to
      investigate space-occupying lesions.

PMID- 26208337
TI  - Spontaneous neurotransmission signals through store-driven Ca(2+) transients to
      maintain synaptic homeostasis.
AB  - Spontaneous glutamate release-driven NMDA receptor activity exerts a strong
      influence on synaptic homeostasis. However, the properties of Ca(2+) signals that
      mediate this effect remain unclear. Here, using hippocampal neurons labeled with
      the fluorescent Ca(2+) probes Fluo-4 or GCAMP5, we visualized action potential
      independent Ca(2+) transients in dendritic regions adjacent to fluorescently
      labeled presynaptic boutons in physiological levels of extracellular Mg(2+).
      These Ca(2+) transients required NMDA receptor activity, and their propensity
      correlated with acute or genetically induced changes in spontaneous
      neurotransmitter release. In contrast, they were insensitive to blockers of AMPA
      receptors, L-type voltage-gated Ca(2+) channels, or group I mGluRs. However,
      inhibition of Ca(2+)-induced Ca(2+) release suppressed these transients and
      elicited synaptic scaling, a process which required protein translation and
      eukaryotic elongation factor-2 kinase activity. These results support a critical
      role for Ca(2+)-induced Ca(2+) release in amplifying NMDA receptor-driven Ca(2+)
      signals at rest for the maintenance of synaptic homeostasis. 

PMID- 26208336
TI  - Tubulin cofactors and Arl2 are cage-like chaperones that regulate the soluble
      alphabeta-tubulin pool for microtubule dynamics.
AB  - Microtubule dynamics and polarity stem from the polymerization of alphabeta
      tubulin heterodimers. Five conserved tubulin cofactors/chaperones and the Arl2
      GTPase regulate alpha- and beta-tubulin assembly into heterodimers and maintain
      the soluble tubulin pool in the cytoplasm, but their physical mechanisms are
      unknown. Here, we reconstitute a core tubulin chaperone consisting of tubulin
      cofactors TBCD, TBCE, and Arl2, and reveal a cage-like structure for regulating
      alphabeta-tubulin. Biochemical assays and electron microscopy structures of
      multiple intermediates show the sequential binding of alphabeta-tubulin dimer
      followed by tubulin cofactor TBCC onto this chaperone, forming a ternary complex
      in which Arl2 GTP hydrolysis is activated to alter alphabeta-tubulin
      conformation. A GTP-state locked Arl2 mutant inhibits ternary complex
      dissociation in vitro and causes severe defects in microtubule dynamics in vivo.
      Our studies suggest a revised paradigm for tubulin cofactors and Arl2 functions
      as a catalytic chaperone that regulates soluble alphabeta-tubulin assembly and
      maintenance to support microtubule dynamics. 

PMID- 26208338
TI  - Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes
      dopamine neuron excitation.
AB  - One reported mechanism for morphine activation of dopamine (DA) neurons of the
      ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons.
      Morphine inhibits GABA inhibitory neurons, which shifts the balance between
      inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then
      leads to VTA-DA neuron excitation. However, it is not known whether morphine has
      an additional strengthening effect on excitatory input. Our results suggest that
      glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via
      GABAB receptors and that morphine promotes presynaptic glutamate release by
      removing this inhibition. We also studied the contribution of the morphine
      induced disinhibitory effect on the presynaptic glutamate release to the overall
      excitatory effect of morphine on VTA-DA neurons and related behavior. Our results
      suggest that the disinhibitory action of morphine on presynaptic glutamate
      release might be the main mechanism for morphine-induced increase in VTA-DA
      neuron firing and related behaviors. 

PMID- 26208340
TI  - Beyond victimhood. The struggle of Munich anatomist Titus von Lanz during
      National Socialism.
AB  - The article analyzes the life and career of the anatomist Titus von Lanz (1897
      1967) of Munich focusing on the period of National Socialism (NS). Von Lanz lost
      his position as an associate professor at the Anatomical Institute of Munich
      University because of his marriage to a "half-Jewish" woman in 1938. In contrast
      to most of his colleagues affected by National Socialist measures, von Lanz had
      opportunities to save his career and made extensive use of them. His story is
      that of a complicated struggle for the continuation of his work, involving a wide
      range of supporters from prestigious physicians to high-ranking National
      Socialist officials as well as the alienation of his colleagues at the Munich
      department of anatomy. The article tries to clarify these developments through
      the presentation of his social background, his supporters, his enemies, the
      research he conducted during NS and von Lanz' own remembrance of these
      developments from the post-war period. It aims at laying out a critical
      appreciation of his motives and actions, thereby contributing to the
      understanding of individual behavior of anatomists under NS. 

PMID- 26208339
TI  - Starvation promotes concerted modulation of appetitive olfactory behavior via
      parallel neuromodulatory circuits.
AB  - The internal state of an organism influences its perception of attractive or
      aversive stimuli and thus promotes adaptive behaviors that increase its
      likelihood of survival. The mechanisms underlying these perceptual shifts are
      critical to our understanding of how neural circuits support animal cognition and
      behavior. Starved flies exhibit enhanced sensitivity to attractive odors and
      reduced sensitivity to aversive odors. Here, we show that a functional remodeling
      of the olfactory map is mediated by two parallel neuromodulatory systems that act
      in opposing directions on olfactory attraction and aversion at the level of the
      first synapse. Short neuropeptide F sensitizes an antennal lobe glomerulus wired
      for attraction, while tachykinin (DTK) suppresses activity of a glomerulus wired
      for aversion. Thus we show parallel neuromodulatory systems functionally
      reconfigure early olfactory processing to optimize detection of nutrients at the
      risk of ignoring potentially toxic food resources. 

PMID- 26208342
TI  - Tracking Virus Particles in Fluorescence Microscopy Images Using Multi-Scale
      Detection and Multi-Frame Association.
AB  - Automatic fluorescent particle tracking is an essential task to study the
      dynamics of a large number of biological structures at a sub-cellular level. We
      have developed a probabilistic particle tracking approach based on multi-scale
      detection and two-step multi-frame association. The multi-scale detection scheme
      allows coping with particles in close proximity. For finding associations, we
      have developed a two-step multi-frame algorithm, which is based on a temporally
      semiglobal formulation as well as spatially local and global optimization. In the
      first step, reliable associations are determined for each particle individually
      in local neighborhoods. In the second step, the global spatial information over
      multiple frames is exploited jointly to determine optimal associations. The multi
      scale detection scheme and the multi-frame association finding algorithm have
      been combined with a probabilistic tracking approach based on the Kalman filter.
      We have successfully applied our probabilistic tracking approach to synthetic as
      well as real microscopy image sequences of virus particles and quantified the
      performance. We found that the proposed approach outperforms previous approaches.

PMID- 26208343
TI  - Color Sparse Representations for Image Processing: Review, Models, and Prospects.
AB  - Sparse representations have been extended to deal with color images composed of
      three channels. A review of dictionary-learning-based sparse representations for
      color images is made here, detailing the differences between the models, and
      comparing their results on the real and simulated data. These models are
      considered in a unifying framework that is based on the degrees of freedom of the
      linear filtering/transformation of the color channels. Moreover, this allows it
      to be shown that the scalar quaternionic linear model is equivalent to
      constrained matrix-based color filtering, which highlights the filtering
      implicitly applied through this model. Based on this reformulation, the new color
      filtering model is introduced, using unconstrained filters. In this model,
      spatial morphologies of color images are encoded by atoms, and colors are encoded
      by color filters. Color variability is no longer captured in increasing the
      dictionary size, but with color filters, this gives an efficient color
      representation. 

PMID- 26208344
TI  - A Random Algorithm for Low-Rank Decomposition of Large-Scale Matrices With
      Missing Entries.
AB  - A random submatrix method (RSM) is proposed to calculate the low-rank
      decomposition U(m*r)V(n*r)(T) (r < m, n) of the matrix Y?R(m*n) (assuming m > n
      generally) with known entry percentage 0 < rho <= 1. RSM is very fast as only
      O(mr(2)rho(r)) or O(n(3)rho(3r)) floating-point operations (flops) are required,
      compared favorably with O(mnr+r(2)(m+n)) flops required by the state-of-the-art
      algorithms. Meanwhile, RSM has the advantage of a small memory requirement as
      only max(n(2),mr+nr) real values need to be saved. With the assumption that known
      entries are uniformly distributed in Y, submatrices formed by known entries are
      randomly selected from Y with statistical size k*nrho(k) or mrho(l)*l , where k
      or l takes r+1 usually. We propose and prove a theorem, under random noises the
      probability that the subspace associated with a smaller singular value will turn
      into the space associated to anyone of the r largest singular values is smaller.
      Based on the theorem, the nrho(k)-k null vectors or the l-r right singular
      vectors associated with the minor singular values are calculated for each
      submatrix. The vectors ought to be the null vectors of the submatrix formed by
      the chosen nrho(k) or l columns of the ground truth of V(T). If enough
      submatrices are randomly chosen, V and U can be estimated accordingly. The
      experimental results on random synthetic matrices with sizes such as 13 1072
      *10(24) and on real data sets such as dinosaur indicate that RSM is 4.30 ~ 197.95
      times faster than the state-of-the-art algorithms. It, meanwhile, has
      considerable high precision achieving or approximating to the best.

PMID- 26208341
TI  - Maraviroc Intensification of cART in Patients with Suboptimal Immunological
      Recovery: A 48-Week, Placebo-Controlled Randomized Trial.
AB  - OBJECTIVE: The immunomodulatory effects of the CCR5-antagonist maraviroc might be
      beneficial in patients with a suboptimal immunological response, but results of
      different cART (combination antiretroviral therapy) intensification studies are
      conflicting. Therefore, we performed a 48-week placebo-controlled trial to
      determine the effect of maraviroc intensification on CD4+ T-cell counts and
      immune activation in these patients. DESIGN: Double-blind, placebo-controlled,
      randomized trial. METHODS: Major inclusion criteria were 1. CD4+ T-cell count
      <350 cells/MUL while at least two years on cART or CD4+ T-cell count <200
      cells/MUL while at least one year on cART, and 2. viral suppression for at least
      the previous 6 months. HIV-infected patients were randomized to add maraviroc (41
      patients) or placebo (44 patients) to their cART regimen for 48 weeks. Changes in
      CD4+ T-cell counts (primary endpoint) and other immunological parameters were
      modeled using linear mixed effects models. RESULTS: No significant differences
      for the modelled increase in CD4+ T-cell count (placebo 15.3 CD4+ T cells/MUL
      (95% confidence interval (CI) [1.0, 29.5] versus maraviroc arm 22.9 CD4+ T
      cells/MUL (95% CI [7.4, 38.5] p = 0.51) or alterations in the expression of
      markers for T-cell activation, proliferation and microbial translocation were
      found between the arms. However, maraviroc intensification did increase the
      percentage of CCR5 expressing CD4+ and CD8+ T-cells, and the plasma levels of the
      CCR5 ligand MIP-1beta. In contrast, the percentage of ex-vivo apoptotic CD8+ and
      CD4+ T-cells decreased in the maraviroc arm. CONCLUSIONS: Maraviroc
      intensification of cART did not increase CD4+ T-cell restoration or decrease
      immune activation as compared to placebo. However, ex-vivo T-cell apoptosis was
      decreased in the maraviroc arm. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00875368.

PMID- 26208345
TI  - Fast Fusion of Multi-Band Images Based on Solving a Sylvester Equation.
AB  - This paper proposes a fast multi-band image fusion algorithm, which combines a
      high-spatial low-spectral resolution image and a low-spatial high-spectral
      resolution image. The well admitted forward model is explored to form the
      likelihoods of the observations. Maximizing the likelihoods leads to solving a
      Sylvester equation. By exploiting the properties of the circulant and
      downsampling matrices associated with the fusion problem, a closed-form solution
      for the corresponding Sylvester equation is obtained explicitly, getting rid of
      any iterative update step. Coupled with the alternating direction method of
      multipliers and the block coordinate descent method, the proposed algorithm can
      be easily generalized to incorporate prior information for the fusion problem,
      allowing a Bayesian estimator. Simulation results show that the proposed
      algorithm achieves the same performance as the existing algorithms with the
      advantage of significantly decreasing the computational complexity of these
      algorithms. 

PMID- 26208346
TI  - Texture Synthesis Using the Structure Tensor.
AB  - This paper proposes a two-stage texture synthesis algorithm. At the first stage,
      a structure tensor map carrying information about the local orientation is
      synthesized from the exemplar's data and used at the second stage to constrain
      the synthesis of the texture. Keeping in mind that the algorithm should be able
      to reproduce as faithfully as possible the visual aspect, statistics, and
      morphology of the input sample, the method is tested on various textures and
      compared objectively with existing methods, highlighting its strength in
      successfully synthesizing the output texture in many situations where traditional
      algorithms fail to reproduce the exemplar's patterns. The promising results pave
      the way towards the synthesis of accurately large and multi-scale patterns as it
      is the case for carbon material samples showing laminar structures, for example. 

PMID- 26208347
TI  - A Douglas-Rachford Splitting Approach to Compressed Sensing Image Recovery Using
      Low-Rank Regularization.
AB  - In this paper, we study the compressed sensing (CS) image recovery problem. The
      traditional method divides the image into blocks and treats each block as an
      independent sub-CS recovery task. This often results in losing global structure
      of an image. In order to improve the CS recovery result, we propose a nonlocal
      (NL) estimation step after the initial CS recovery for denoising purpose. The NL
      estimation is based on the well-known NL means filtering that takes an advantage
      of self-similarity in images. We formulate the NL estimation as the low-rank
      matrix approximation problem, where the low-rank matrix is formed by the NL
      similarity patches. An efficient algorithm, nonlocal Douglas-Rachford (NLDR),
      based on Douglas-Rachford splitting is developed to solve this low-rank
      optimization problem constrained by the CS measurements. Experimental results
      demonstrate that the proposed NLDR algorithm achieves significant performance
      improvements over the state-of-the-art in CS image recovery. 

PMID- 26208348
TI  - Consistent Video Saliency Using Local Gradient Flow Optimization and Global
      Refinement.
AB  - We present a novel spatiotemporal saliency detection method to estimate salient
      regions in videos based on the gradient flow field and energy optimization. The
      proposed gradient flow field incorporates two distinctive features: 1) intra
      frame boundary information and 2) inter-frame motion information together for
      indicating the salient regions. Based on the effective utilization of both intra
      frame and inter-frame information in the gradient flow field, our algorithm is
      robust enough to estimate the object and background in complex scenes with
      various motion patterns and appearances. Then, we introduce local as well as
      global contrast saliency measures using the foreground and background information
      estimated from the gradient flow field. These enhanced contrast saliency cues
      uniformly highlight an entire object. We further propose a new energy function to
      encourage the spatiotemporal consistency of the output saliency maps, which is
      seldom explored in previous video saliency methods. The experimental results show
      that the proposed algorithm outperforms state-of-the-art video saliency detection
      methods. 

PMID- 26208349
TI  - Objective Quality Assessment for Color-to-Gray Image Conversion.
AB  - Color-to-gray (C2G) image conversion is the process of transforming a color image
      into a grayscale one. Despite its wide usage in real-world applications, little
      work has been dedicated to compare the performance of C2G conversion algorithms.
      Subjective evaluation is reliable but is also inconvenient and time consuming.
      Here, we make one of the first attempts to develop an objective quality model
      that automatically predicts the perceived quality of C2G converted images.
      Inspired by the philosophy of the structural similarity index, we propose a C2G
      structural similarity (C2G-SSIM) index, which evaluates the luminance, contrast,
      and structure similarities between the reference color image and the C2G
      converted image. The three components are then combined depending on image type
      to yield an overall quality measure. Experimental results show that the proposed
      C2G-SSIM index has close agreement with subjective rankings and significantly
      outperforms existing objective quality metrics for C2G conversion. To explore the
      potentials of C2G-SSIM, we further demonstrate its use in two applications: 1)
      automatic parameter tuning for C2G conversion algorithms and 2) adaptive fusion
      of C2G converted images. 

PMID- 26208350
TI  - Genetic Variants of SNCA Are Associated with Susceptibility to Parkinson's
      Disease but Not Amyotrophic Lateral Sclerosis or Multiple System Atrophy in a
      Chinese Population.
AB  - BACKGROUND: The polymorphisms of alpha-synuclein (SNCA), rs3775444, rs3822086 and
      rs11931074 that are strongly associated with Parkinson's disease (PD) in
      Caucasian populations, were examined in this study to elucidate the role of
      polymorphisms in different ethnic backgrounds. The possible associations of these
      three polymorphisms were also investigated in PD, amyotrophic lateral sclerosis
      (ALS), and multiple system atrophy (MSA) in a Chinese population based on the
      overlapping of clinical manifestations and pathological characteristics of these
      three neurodegenerative diseases. METHODS: A total of 1276 PD, 885 sporadic ALS
      (SALS), 364 MSA patients, and 846 healthy controls (HCs) were included. All
      subjects were genotyped for the three polymorphisms using Sequenom iPLEX Assay
      technology. RESULTS: Significant differences in the genotype distributions (p =
      5.99E-06 and p = 4.98E-06, respectively) and the minor allele frequency (MAF) (p
      = 2.16E-06 and p = 2.15E-06, respectively) of SNCA rs3822086 (C) and rs11931074
      (G) were observed between PD and HCs. However, no differences were found in the
      genotype distributions and MAF of SNCA rs3775444 (T) between PD and HCs.
      Haplotype that incorporated the three SNPs further strengthened the association
      with PD (best haplotype, p = 9.62E-005). No significant differences in the
      genotype distributions and MAF of the SNPs were found between SALS and HCs, MSA
      and HCs, and subgroups of PD and SALS. However, the MAF of SNCA rs3775444 (T) was
      significantly higher in MSA patients with frontal lobe dysfunction than MSA
      patients without dysfunction (p = 0.0002, OR 2.53, 95%CI: 1.55-4.15). CONCLUSION:
      Our results suggest that the rs3822086 (C) allele and rs11931074 (G) allele in
      SNCA decrease the risk for PD, and SNCA rs11931074 may affect frontal lobe
      dysfunction of MSA in the Chinese population. However, these SNCA polymorphisms
      are not likely a common cause of SALS or MSA.

PMID- 26208352
TI  - Gender Differences in the Symptoms, Signs, Disease History, Lesion Position and
      Pathophysiology in Patients with Pulmonary Embolism.
AB  - Advances in research relating to pulmonary embolisms (PE) can assist physicians
      in selecting the best management strategies for PE patients. However, the
      symptoms, signs, disease history, lesion position and pathophysiology linked to
      different genders in patients with PE have rarely been evaluated. One hundred and
      forty-nine PE patients (73 males and 76 females) were sequentially recruited to
      this study over the last five years whilst attending our Emergency Department.
      Data relating to the symptoms, signs, disease history, biochemical testing,
      cardiac electrophysiology, imaging detection, treatment and outcome were
      collected and the gender differences were analyzed. We found that embolisms
      occurred significantly more frequently in the right lung (89.7%) than in the left
      lung (42.6%). The presence of dyspnea, the number of patients presenting with
      tumors, the number of patients with chronic pulmonary disease, those with emboli
      in the right pulmonary artery and emboli in the right lung, as well as the
      average systolic and diastolic blood pressure were: 78.1%, 15.1%, 31.5%, 32.9%,
      94.5%, 129.9+20.0 and 75.0+11.2 in the male patients and 59.2%, 1.3%, 14.5%,
      17.1%, 69.7%, 125.1+14.6 and 69.3+11.0 in the female patients. These indicators
      were found to be significantly higher in male patients. In contrast, the rate of
      V1-V4 T-wave inversion and level of D-dimer in the blood were significantly lower
      in males than in females. No significant difference was observed in the remaining
      observational indicators. Gender differences regarding the symptoms, signs,
      disease history, lesion position and pathophysiology exist in patients with PE
      and should be considered in clinical practice. 

PMID- 26208351
TI  - Divide and Conquer May Not Be the Optimal Approach to Retain the Desirable
      Estrogenic Attributes of the Cyclopia Nutraceutical Extract, SM6Met.
AB  - The genus Cyclopia, an indigenous South African fynbos plant used to prepare
      honeybush tea, contains phytoestrogenic compounds. An extract from C. subternata,
      SM6Met, displays three desirable estrogenic attributes for future development of
      a phytoestrogenic nutraceutical, namely, ERalpha antagonism, ERbeta agonism, and
      also antagonism of E2-induced breast cancer cell proliferation. Activity-guided
      fractionation of SM6Met was used in an attempt to isolate and identify compounds
      conferring the desirable estrogenic profile to SM6Met. Initial liquid-liquid
      fractionation of SM6Met yielded a polar fraction (PF) and a non-polar fraction
      (NPF), with the desirable estrogenic attributes retained in the NPF. Subsequent
      high performance counter-current chromatography (HPCCC) fractionation of the NPF
      yielded three fractions (F1-F3). Interestingly, the fractions revealed separation
      of the previously demonstrated positive estrogenic attributes of the NPF into
      separate fractions, with F1 and F2 acting as ERalpha antagonists, only F2
      inducing antagonism of E2-induced breast cancer cell proliferation and only F3
      retaining robust ERbeta agonist activity. In terms of major polyphenols,
      quantitative HPLC and liquid chromatography tandem mass spectrometry (LC-MS/MS)
      indicated that HPCCC fractionation resulted in a divergence of polyphenolic
      classes, with F1 emerging as the dihydrochalcone-rich fraction and F2 as the
      flavanone- and benzophenone-rich fraction, while the xanthones, flavones and
      phenolic acids were retained in F3. F3 was re-engineered into F3R by reassembling
      the major polyphenols identified in the fraction. F3R could, however, not
      replicate the effect of F3. In conclusion, although activity-guided fractionation
      results suggest that retention of all the desirable estrogenic attributes of the
      original SM6Met in one fraction is not an attainable goal, fractionation is a
      useful tool to enhance specific desirable estrogenic attributes. 

PMID- 26208353
TI  - Fractionated Radiation Exposure of Rat Spinal Cords Leads to Latent Neuro
      Inflammation in Brain, Cognitive Deficits, and Alterations in Apurinic
      Endonuclease 1.
AB  - Ionizing radiation causes degeneration of myelin, the insulating sheaths of
      neuronal axons, leading to neurological impairment. As radiation research on the
      central nervous system has predominantly focused on neurons, with few studies
      addressing the role of glial cells, we have focused our present research on
      identifying the latent effects of single/ fractionated -low dose of low/ high
      energy radiation on the role of base excision repair protein Apurinic
      Endonuclease-1, in the rat spinal cords oligodendrocyte progenitor cells'
      differentiation. Apurinic endonuclease-1 is predominantly upregulated in response
      to oxidative stress by low- energy radiation, and previous studies show
      significant induction of Apurinic Endonuclease-1 in neurons and astrocytes. Our
      studies show for the first time, that fractionation of protons cause latent
      damage to spinal cord architecture while fractionation of HZE (28Si) induce
      increase in APE1 with single dose, which then decreased with fractionation. The
      oligodendrocyte progenitor cells differentiation was skewed with increase in
      immature oligodendrocytes and astrocytes, which likely cause the observed
      decrease in white matter, increased neuro-inflammation, together leading to the
      observed significant cognitive defects. 

PMID- 26208354
TI  - Implementation of genome-wide complex trait analysis to quantify the heritability
      in multiple myeloma.
AB  - A sizeable fraction of multiple myeloma (MM) is expected to be explained by
      heritable factors. Genome-wide association studies (GWAS) have successfully
      identified a number of common single-nucleotide polymorphisms (SNPs) influencing
      MM risk. While these SNPs only explain a small proportion of the genetic risk it
      is unclear how much is left to be detected by other, yet to be identified, common
      SNPs. Therefore, we applied Genome-Wide Complex Trait Analysis (GCTA) to 2,282
      cases and 5,197 controls individuals to estimate the heritability of MM. We
      estimated that the heritability explained by known common MM risk SNPs identified
      in GWAS was 2.9% (+/- 2.4%), whereas the heritability explained by all common
      SNPs was 15.2% (+/- 2.8%). Comparing the heritability explained by the common
      variants with that from family studies, a fraction of the heritability may be
      explained by other genetic variants, such as rare variants. In summary, our
      results suggest that known MM SNPs only explain a small proportion of the
      heritability and more common SNPs remain to be identified.

PMID- 26208355
TI  - Spatiotemporal Clustering Analysis and Risk Assessments of Human Cutaneous
      Anthrax in China, 2005-2012.
AB  - OBJECTIVE: To investigate the epidemic characteristics of human cutaneous anthrax
      (CA) in China, detect the spatiotemporal clusters at the county level for
      preemptive public health interventions, and evaluate the differences in the
      epidemiological characteristics within and outside clusters. METHODS: CA cases
      reported during 2005-2012 from the national surveillance system were evaluated at
      the county level using space-time scan statistic. Comparative analysis of the
      epidemic characteristics within and outside identified clusters was performed
      using using the chi2 test or Kruskal-Wallis test. RESULTS: The group of 30-39
      years had the highest incidence of CA, and the fatality rate increased with age,
      with persons >=70 years showing a fatality rate of 4.04%. Seasonality analysis
      showed that most of CA cases occurred between May/June and September/October of
      each year. The primary spatiotemporal cluster contained 19 counties from June
      2006 to May 2010, and it was mainly located straddling the borders of Sichuan,
      Gansu, and Qinghai provinces. In these high-risk areas, CA cases were
      predominantly found among younger, local, males, shepherds, who were living on
      agriculture and stockbreeding and characterized with high morbidity, low
      mortality and a shorter period from illness onset to diagnosis. CONCLUSION: CA
      was geographically and persistently clustered in the Southwestern China during
      2005-2012, with notable differences in the epidemic characteristics within and
      outside spatiotemporal clusters; this demonstrates the necessity for CA
      interventions such as enhanced surveillance, health education, mandatory and
      standard decontamination or disinfection procedures to be geographically targeted
      to the areas identified in this study.

PMID- 26208358
TI  - Phase Synchronization Between Motor Cortices During Gait Movement in Patients
      With Spinal Cord Injury.
AB  - Spinal cord injury (SCI) frequently leads to generalized locomotor disability and
      gait disturbances which cause serious discomfort among patients. Human gait is a
      complex process in the central nervous system that results from the integration
      of various mechanisms which remain unclear. Therefore, it is of great theoretical
      and practical significance to investigate the cortical activity patterns during
      gait movement in SCI. In this study, brain activity was recorded by
      electroencephalogram (EEG) during two kinds of gait-like movements. Phase
      synchronization between motor cortices was investigated through source analysis
      and phase locking. Results revealed that diverse neural networks with different
      resonance-like frequencies exist in the brain. Further, we found that the
      premotor cortex played an important role in the control of passive gait-like
      movement. In attempted/active movement, spatial function and multimodal
      integration with somatosensory information are crucial aspects of posterior
      parietal cortex function which need to be considered separately in different EEG
      bands. Our results further confirmed that neural system control patterns in
      passive gait-like movement differ from those in attempted or active gait-like
      movement. Novel insights into human gait will provide a basis for improvements in
      future neurorehabilitation applications. 

PMID- 26208357
TI  - Digital Gene Expression Analysis to Screen Disease Resistance-Relevant Genes from
      Leaves of Herbaceous Peony (Paeonia lactiflora Pall.) Infected by Botrytis
      cinerea.
AB  - Herbaceous peony (Paeonia lactiflora Pall.) is a well-known traditional flower in
      China and is widely used for landscaping and garden greening due to its high
      ornamental value. However, disease spots usually appear after the flowering of
      the plant and may result in the withering of the plant in severe cases. This
      study examined the disease incidence in an herbaceous peony field in the Yangzhou
      region, Jiangsu Province. Based on morphological characteristics and molecular
      data, the disease in this area was identified as a gray mold caused by Botrytis
      cinerea. Based on previously obtained transcriptome data, eight libraries
      generated from two herbaceous peony cultivars 'Zifengyu' and 'Dafugui' with
      different susceptibilities to the disease were then analyzed using digital gene
      expression profiling (DGE). Thousands of differentially expressed genes (DEGs)
      were screened by comparing the eight samples, and these genes were annotated
      using the Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG)
      database. The pathways related to plant-pathogen interaction, secondary
      metabolism synthesis and antioxidant system were concentrated, and 51, 76, and 13
      disease resistance-relevant candidate genes were identified, respectively. The
      expression patterns of these candidate genes differed between the two cultivars:
      their expression of the disease-resistant cultivar 'Zifengyu' sharply increased
      during the early stages of infection, while it was relatively subdued in the
      disease-sensitive cultivar 'Dafugui'. A selection of ten candidate genes was
      evaluated by quantitative real-time PCR (qRT-PCR) to validate the DGE data. These
      results revealed the transcriptional changes that took place during the
      interaction of herbaceous peony with B. cinerea, providing insight into the
      molecular mechanisms of host resistance to gray mold. 

PMID- 26208356
TI  - A Chimeric HIV-1 gp120 Fused with Vaccinia Virus 14K (A27) Protein as an HIV
      Immunogen.
AB  - In the HIV vaccine field, there is a need to produce highly immunogenic forms of
      the Env protein with the capacity to trigger broad B and T-cell responses. Here,
      we report the generation and characterization of a chimeric HIV-1 gp120 protein
      (termed gp120-14K) by fusing gp120 from clade B with the vaccinia virus (VACV)
      14K oligomeric protein (derived from A27L gene). Stable CHO cell lines expressing
      HIV-1 gp120-14K protein were generated and the protein purified was characterized
      by size exclusion chromatography, electron microscopy and binding to anti-Env
      antibodies. These approaches indicate that gp120-14K protein is oligomeric and
      reacts with a wide spectrum of HIV-1 neutralizing antibodies. Furthermore, in
      human monocyte-derived dendritic cells (moDCs), gp120-14K protein upregulates the
      levels of several proinflammatory cytokines and chemokines associated with Th1
      innate immune responses (IL-1beta, IFN-gamma, IL-6, IL-8, IL-12, RANTES).
      Moreover, we showed in a murine model, that a heterologous prime/boost
      immunization protocol consisting of a DNA prime with a plasmid expressing gp120
      14K protein followed by a boost with MVA-B [a recombinant modified vaccinia virus
      Ankara (MVA) expressing HIV-1 gp120, Gag, Pol and Nef antigens from clade B],
      generates stronger, more polyfunctional, and greater effector memory HIV-1
      specific CD4+ and CD8+ T-cell immune responses, than immunization with DNA
      gp120/MVA-B. The DNA/MVA protocol was superior to immunization with the
      combination of protein/MVA and the latter was superior to a prime/boost of
      MVA/MVA or protein/protein. In addition, these immunization protocols enhanced
      antibody responses against gp120 of the class IgG2a and IgG3, together favoring a
      Th1 humoral immune response. These results demonstrate that fusing HIV-1 gp120
      with VACV 14K forms an oligomeric protein which is highly antigenic as it
      activates a Th1 innate immune response in human moDCs, and in vaccinated mice
      triggers polyfunctional HIV-1-specific adaptive and memory T-cell immune
      responses, as well as humoral responses. This novel HIV-1 gp120-14K immunogen
      might be considered as an HIV vaccine candidate for broad T and B-cell immune
      responses. 

PMID- 26208359
TI  - Coordination of Reach-to-Grasp Kinematics in Individuals With Childhood-Onset
      Dystonia Due to Hemiplegic Cerebral Palsy.
AB  - Functional reaching is impaired in dystonia. Here, we analyze upper extremity
      kinematics to quantify timing and coordination abnormalities during unimanual
      reach-to-grasp movements in individuals with childhood-onset unilateral wrist
      dystonia. Kinematics were measured during movements of both upper limbs in a
      patient group ( n = 11, age = 17.5 +/-5 years), and a typically developing
      control group ( n = 9, age = 16.6 +/-5 years). Hand aperture was computed to
      study the coordination of reach and grasp. Time-varying joint synergies within
      one upper limb were calculated using a novel technique based on principal
      component analysis to study intra-limb coordination. In the non-dominant arm,
      results indicate reduced coordination between reach and grasp in patients who
      could not lift the grasped object compared to those who could lift it. Lifters
      exhibit incoordination in distal upper extremity joints later in the movement and
      non-lifters lacked coordination throughout the movement and in the whole upper
      limb. The amount of atypical coordination correlates with dystonia severity in
      patients. Reduced coordination during movement may reflect deficits in the
      execution of simultaneous movements, motor planning, or muscle activation.
      Rehabilitation efforts can focus on particular time points when kinematic
      patterns deviate abnormally to improve functional reaching in individuals with
      childhood-onset dystonia.

PMID- 26208360
TI  - Epileptic Seizure Prediction by Exploiting Spatiotemporal Relationship of EEG
      Signals Using Phase Correlation.
AB  - Automated seizure prediction has a potential in epilepsy monitoring, diagnosis,
      and rehabilitation. Electroencephalogram (EEG) is widely used for seizure
      detection and prediction. This paper proposes a new seizure prediction approach
      based on spatiotemporal relationship of EEG signals using phase correlation. This
      measures the relative change between current and reference vectors of EEG signals
      which can be used to identify preictal/ictal (before the actual seizure onset/
      actual seizure period) and interictal (period between adjacent seizures) EEG
      signals to predict the seizure. The experiments show that the proposed method is
      less sensitive to artifacts and provides higher prediction accuracy (i.e.,
      91.95%) and lower number of false alarms compared to the state-of-the-art methods
      using intracranial EEG signals in different brain locations of 21 patients from a
      benchmark data set. 

PMID- 26208361
TI  - Influence of Metallic Nanoparticles on Blood Flow Through Arteries Having Both
      Stenosis and Aneurysm.
AB  - The main objective of the present paper is to discuss the blood flow analysis
      through inclined arteries by treating its nature as viscous fluid. The effects of
      both dilatation and constriction are considered to investigate the behavior of
      the both abnormal wall segments with variable nanofluid viscosity. The nonlinear
      momentum equation for proposed model is simplified by considering the
      nondimensionless parameters to find the exact solutions of the formulated
      problem. The main hemodynamic effects of stenosis and aneurysm are discussed for
      different values of the interest by plotting the graphs of wall shear stress and
      resistance impedance to flow and opposite behavior is observed for both cases.
      The results also reveal that the nanoparticles with high concentration are
      important to reduce the resistance impedance to blood flow. The graphs of stream
      lines show the formation of bolus appears in the aneurysm segment but no
      formation is observed or seen in the stenotic segment. 

PMID- 26208362
TI  - Advancing the Accuracy of Protein Fold Recognition by Utilizing Profiles From
      Hidden Markov Models.
AB  - Protein fold recognition is an important step towards solving protein function
      and tertiary structure prediction problems. Among a wide range of approaches
      proposed to solve this problem, pattern recognition based techniques have
      achieved the best results. The most effective pattern recognition-based
      techniques for solving this problem have been based on extracting evolutionary
      based features. Most studies have relied on the Position Specific Scoring Matrix
      (PSSM) to extract these features. However it is known that profile-profile
      sequence alignment techniques can identify more remote homologs than sequence
      profile approaches like PSIBLAST. In this study we use a profile-profile sequence
      alignment technique, namely HHblits, to extract HMM profiles. We will show that
      unlike previous studies, using the HMM profile to extract evolutionary
      information can significantly enhance the protein fold prediction accuracy. We
      develop a new pattern recognition based system called HMMFold which extracts HMM
      based evolutionary information and captures remote homology information better
      than previous studies. Using HMMFold we achieve up to 93.8% and 86.0% prediction
      accuracies when the sequential similarity rates are less than 40% and 25%,
      respectively. These results are up to 10% better than previously reported results
      for this task. Our results show significant enhancement especially for benchmarks
      with sequential similarity as low as 25% which highlights the effectiveness of
      HMMFold to address this problem and its superiority over previously proposed
      approaches found in the literature. The HMMFold is available online at:
      http://sparks-lab.org/pmwiki/download/index.php?Download =HMMFold.tar.bz2. 

PMID- 26208363
TI  - Rendered and Characterized Closed-Loop Accuracy of Impedance-Type Haptic
      Displays.
AB  - Impedance-type kinesthetic haptic displays aim to render arbitrary desired
      dynamics to a human operator using force feedback. To render realistic virtual
      environments, the difference between desired and rendered dynamics must be small.
      In this paper, we analyze the closed-loop dynamics of haptic displays for three
      common virtual environments: a spring, a damper, and a spring-damper, including
      the effects of time delay and low-pass filtering. Using a linear model, we
      identify important parameters for the rendered dynamics in terms of effective
      impedances, a conceptual tool that decomposes the displays closed-loop impedance
      into components with physical analogs. Our results establish bandwidth limits for
      rendering effective stiffness and damping. The effective stiffness bandwidth is
      limited by the virtual stiffness and device mass, and the effective damping
      bandwidth is limited by the cut-off frequency of the low-pass filter which
      filters the device velocity estimate. We show that a general system impedance can
      be characterized by a mass, damper, and spring optimally by the solution to a
      convex optimization problem, and we present a quantitative metric, the Average
      Distortion Error (ADE), to describe the fidelity of this model. Time delay has no
      significant effect on characterized stiffness, and reduces characterized damping
      by the product of virtual stiffness and total time delay. Reducing the low-pass
      filter cut-off frequency reduces the characterized damping. Experimental data
      gathered with a Phantom Premium 1.5 validates the theoretical analysis. We also
      conducted human user experiments to investigate the effects of time delay and low
      pass filtering on perceived stiffness and damping. Similar to the characterized
      dynamics results, we observed no significant effect of time delay on perceived
      stiffness, and increasing time delay resulted in reduced perceived damping. Lower
      filter cut-off frequencies resulted in lower perceived damping. This work informs
      haptic display design by presenting how closed-loop behavior changes with key
      parameters.

PMID- 26208365
TI  - Compound Rank- k Projections for Bilinear Analysis.
AB  - In many real-world applications, data are represented by matrices or high-order
      tensors. Despite the promising performance, the existing 2-D discriminant
      analysis algorithms employ a single projection model to exploit the discriminant
      information for projection, making the model less flexible. In this paper, we
      propose a novel compound rank- k projection (CRP) algorithm for bilinear
      analysis. The CRP deals with matrices directly without transforming them into
      vectors, and it, therefore, preserves the correlations within the matrix and
      decreases the computation complexity. Different from the existing 2-D
      discriminant analysis algorithms, objective function values of CRP increase
      monotonically. In addition, the CRP utilizes multiple rank- k projection models
      to enable a larger search space in which the optimal solution can be found. In
      this way, the discriminant ability is enhanced. We have tested our approach on
      five data sets, including UUIm, CVL, Pointing'04, USPS, and Coil20. Experimental
      results show that the performance of our proposed CRP performs better than other
      algorithms in terms of classification accuracy.

PMID- 26208364
TI  - Enhancing the Performance of Passive Teleoperation Systems via Cutaneous
      Feedback.
AB  - We introduce a novel method to improve the performance of passive teleoperation
      systems with force reflection. It consists of integrating kinesthetic haptic
      feedback provided by common grounded haptic interfaces with cutaneous haptic
      feedback. The proposed approach can be used on top of any time-domain control
      technique that ensures a stable interaction by scaling down kinesthetic feedback
      when this is required to satisfy stability conditions (e.g., passivity) at the
      expense of transparency. Performance is recovered by providing a suitable amount
      of cutaneous force through custom wearable cutaneous devices. The viability of
      the proposed approach is demonstrated through an experiment of perceived
      stiffness and an experiment of teleoperated needle insertion in soft tissue.

PMID- 26208366
TI  - Stability Analysis for Delayed Neural Networks Considering Both Conservativeness
      and Complexity.
AB  - This paper investigates delay-dependent stability for continuous neural networks
      with a time-varying delay. This paper aims at deriving a new stability criterion,
      considering tradeoff between conservativeness and calculation complexity. A new
      Lyapunov-Krasovskii functional with simple augmented terms and delay-dependent
      terms is constructed, and its derivative is estimated by several techniques,
      including free-weighting matrix and inequality estimation methods. Then, the
      influence of the techniques used on the conservativeness and the complexity is
      analyzed one by one. Moreover, useful guidelines for improving criterion and
      future work are briefly discussed. Finally, the advantages of the proposed
      criterion compared with the existing ones are verified based on three numerical
      examples.

PMID- 26208367
TI  - Use of Semisupervised Clustering and Feature-Selection Techniques for
      Identification of Co-expressed Genes.
AB  - Studying the patterns hidden in gene-expression data helps to understand the
      functionality of genes. In general, clustering techniques are widely used for the
      identification of natural partitionings from the gene expression data. In order
      to put constraints on dimensionality, feature selection is the key issue because
      not all features are important from clustering point of view. Moreover some
      limited amount of supervised information can help to fine tune the obtained
      clustering solution. In this paper, the problem of simultaneous feature selection
      and semisupervised clustering is formulated as a multiobjective optimization
      (MOO) task. A modern simulated annealing-based MOO technique namely AMOSA is
      utilized as the background optimization methodology. Here, features and cluster
      centers are represented in the form of a string and the assignment of genes to
      different clusters is done using a point symmetry-based distance. Six
      optimization criteria based on several internal and external cluster validity
      indices are utilized. In order to generate the supervised information, a popular
      clustering technique, Fuzzy C-mean, is utilized. Appropriate subset of features,
      proper number of clusters and the proper partitioning are determined using the
      search capability of AMOSA. The effectiveness of this proposed semisupervised
      clustering technique, Semi-FeaClustMOO, is demonstrated on five publicly
      available benchmark gene-expression datasets. Comparison results with the
      existing techniques for gene-expression data clustering again reveal the
      superiority of the proposed technique. Statistical and biological significance
      tests have also been carried out.

PMID- 26208368
TI  - Human Activity Recognition by Combining a Small Number of Classifiers.
AB  - We consider the problem of daily human activity recognition (HAR) using multiple
      wireless inertial sensors, and specifically, HAR systems with a very low number
      of sensors, each one providing an estimation of the performed activities. We
      propose new Bayesian models to combine the output of the sensors. The models are
      based on a soft outputs combination of individual classifiers to deal with the
      small number of sensors. We also incorporate the dynamic nature of human
      activities as a first-order homogeneous Markov chain. We develop both inductive
      and transductive inference methods for each model to be employed in supervised
      and semisupervised situations, respectively. Using different real HAR databases,
      we compare our classifiers combination models against a single classifier that
      employs all the signals from the sensors. Our models exhibit consistently a
      reduction of the error rate and an increase of robustness against sensor
      failures. Our models also outperform other classifiers combination models that do
      not consider soft outputs and an Markovian structure of the human activities.

PMID- 26208369
TI  - BioWatch: A Noninvasive Wrist-Based Blood Pressure Monitor That Incorporates
      Training Techniques for Posture and Subject Variability.
AB  - Noninvasive continuous blood pressure (BP) monitoring is not yet practically
      available for daily use. Challenges include making the system easily wearable,
      reducing noise level and improving accuracy. Variations in each person's physical
      characteristics, as well as the possibility of different postures, increase the
      complexity of continuous BP monitoring, especially outside the hospital. This
      study attempts to provide an easily wearable solution and proposes training to
      specific posture and individual for further improving accuracy. The wrist watch
      based system we developed can measure electrocardiogram and photoplethysmogram.
      From these two signals, we measure pulse transit time through which we can obtain
      systolic and diastolic blood pressure through regression techniques. In this
      study, we investigate various functions to perform the training to obtain blood
      pressure. We validate measurements on different postures and subjects, and show
      the value of training the device to each posture and each subject. We observed
      that the average RMSE between the measured actual systolic BP and calculated
      systolic BP is between 7.83 to 9.37 mmHg across 11 subjects. The corresponding
      range of error for diastolic BP is 5.77 to 6.90 mmHg. The system can also
      automatically detect the arm position of the user using an accelerometer with an
      average accuracy of 98%, to make sure that the sensor is kept at the proper
      height. This system, called BioWatch, can potentially be a unified solution for
      heart rate, SPO2 and continuous BP monitoring.

PMID- 26208370
TI  - Statistical Metamodeling and Sequential Design of Computer Experiments to Model
      Glyco-Altered Gating of Sodium Channels in Cardiac Myocytes.
AB  - Glycan structures account for up to 35% of the mass of cardiac sodium ( Nav )
      channels. To question whether and how reduced sialylation affects Nav activity
      and cardiac electrical signaling, we conducted a series of in vitro experiments
      on ventricular apex myocytes under two different glycosylation conditions,
      reduced protein sialylation (ST3Gal4(-/-)) and full glycosylation (control).
      Although aberrant electrical signaling is observed in reduced sialylation,
      realizing a better understanding of mechanistic details of pathological
      variations in INa and AP is difficult without performing in silico studies.
      However, computer model of Nav channels and cardiac myocytes involves greater
      levels of complexity, e.g., high-dimensional parameter space, nonlinear and
      nonconvex equations. Traditional linear and nonlinear optimization methods have
      encountered many difficulties for model calibration. This paper presents a new
      statistical metamodeling approach for efficient computer experiments and
      optimization of Nav models. First, we utilize a fractional factorial design to
      identify control variables from the large set of model parameters, thereby
      reducing the dimensionality of parametric space. Further, we develop the Gaussian
      process model as a surrogate of expensive and time-consuming computer models and
      then identify the next best design point that yields the maximal probability of
      improvement. This process iterates until convergence, and the performance is
      evaluated and validated with real-world experimental data. Experimental results
      show the proposed algorithm achieves superior performance in modeling the
      kinetics of Nav channels under a variety of glycosylation conditions. As a
      result, in silico models provide a better understanding of glyco-altered
      mechanistic details in state transitions and distributions of Nav channels.
      Notably, ST3Gal4(-/-) myocytes are shown to have higher probabilities accumulated
      in intermediate inactivation during the repolarization and yield a shorter
      refractory period than WTs. The proposed statistical design of computer
      experiments is generally extensible to many other disciplines that involve large
      scale and computationally expensive models.

PMID- 26208371
TI  - Respiration Disorders Classification With Informative Features for m-Health
      Applications.
AB  - Respiratory disorder is a highly prevalent condition associated with many adverse
      health problems. As the current means of diagnosis are obtrusive and ill-suited
      for real-time m-health applications, we explore a convenient and low-cost
      automatic approach that uses wearable microelectromechanical system sensor
      technology. The proposed system introduces the use of motion sensors to detect
      the changes in the anterior-posterior diameter of the chest wall during breathing
      function as well as extracting the informative respiratory features to be used
      for breathing disorders classification. Extensive evaluations are provided on six
      well-known classifiers with novel feature extraction techniques to distinguish
      among eight different pathological breathing patterns. The effects of the number
      of sensors, sensor placement, as well as feature selection on the classification
      performance are discussed. The experimental results conducted with ten subjects
      show the best accuracy rates of 97.50% by support vector machine and 97.37% with
      decision tree bagging (DTB) with all features and after feature selection,
      correspondingly. Furthermore, a binary classification is proposed for
      distinguishing between healthy people and patients with breath problems. The
      different assessments of classification parameters are provided by measuring the
      accuracy, sensitivity, specificity, F1-score and Mathew correlation coefficient.
      The accuracy rates above 98% suggest superior performance of DTB in binary
      recognition supported by the suggested new features.

PMID- 26208372
TI  - Examining Accumulated Emotional Traits in Suicide Blogs With an Emotion Topic
      Model.
AB  - Suicide has been a major cause of death throughout the world. Recent studies have
      proved a reliable connection between the emotional traits and suicide. However,
      detection and prevention of suicide are mostly carried out in the clinical
      centers, which limit the effective treatments to a restricted group of people. To
      assist detecting suicide risks among the public, we propose a novel method by
      exploring the accumulated emotional information from people's daily writings
      (i.e., Blogs), and examining these emotional traits that are predictive of
      suicidal behaviors. A complex emotion topic model is employed to detect the
      underlying emotions and emotion-related topics in the Blog streams, based on
      eight basic emotion categories and five levels of emotion intensities. Since
      suicide is caused through an accumulative process, we propose three accumulative
      emotional traits, i.e., accumulation, covariance, and transition of the
      consecutive Blog emotions, and employ a generalized linear regression algorithm
      to examine the relationship between emotional traits and suicide risk. Our
      experiment results suggest that the emotion transition trait turns to be more
      discriminative of the suicide risk, and that the combination of three traits in
      linear regression would generate even more discriminative predictions. A
      classification of the suicide and nonsuicide Blog articles in our additional
      experiment verifies this result. Finally, we conduct a case study of the most
      commonly mentioned emotion-related topics in the suicidal Blogs, to further
      understand the association between emotions and thoughts for these authors.

PMID- 26208373
TI  - On the Influence of Confounding Factors in Multisite Brain Morphometry Studies of
      Developmental Pathologies: Application to Autism Spectrum Disorder.
AB  - Pooling data acquired on different MR scanners is a commonly used practice to
      increase the statistical power of studies based on MRI-derived measurements. Such
      studies are very appealing since they should make it possible to detect more
      subtle effects related to pathologies. However, the influence of confounds
      introduced by scanner-related variations remains unclear. When studying brain
      morphometry descriptors, it is crucial to investigate whether scanner-induced
      errors can exceed the effect of the disease itself. More specifically, in the
      context of developmental pathologies such as autism spectrum disorders (ASD), it
      is essential to evaluate the influence of the scanner on age-related effects. In
      this paper, we studied a dataset composed of 159 anatomical MR images pooled from
      three different scanners, including 75 ASD patients and 84 healthy controls. We
      quantitatively assessed the effects of the age, pathology, and scanner factors on
      cortical thickness measurements. Our results indicate that scan pooling from
      different sites would be less fruitful in some cortical regions than in others.
      Although the effect of age is consistent across scanners, the interaction between
      the age and scanner factors is important and significant in some specific
      cortical areas.

PMID- 26208374
TI  - Spectral Multimodal Hashing and Its Application to Multimedia Retrieval.
AB  - In recent years, multimedia retrieval has sparked much research interest in the
      multimedia, pattern recognition, and data mining communities. Although some
      attempts have been made along this direction, performing fast multimodal search
      at very large scale still remains a major challenge in the area. While hashing
      based methods have recently achieved promising successes in speeding-up large
      scale similarity search, most existing methods are only designed for uni-modal
      data, making them unsuitable for multimodal multimedia retrieval. In this paper,
      we propose a new hashing-based method for fast multimodal multimedia retrieval.
      The method is based on spectral analysis of the correlation matrix of different
      modalities. We also develop an efficient algorithm that learns some parameters
      from the data distribution for obtaining the binary codes. We empirically compare
      our method with some state-of-the-art methods on two real-world multimedia data
      sets. 

PMID- 26208375
TI  - Adaptive Norm Selection for Regularized Image Restoration and Super-Resolution.
AB  - In the commonly employed regularization models of image restoration and super
      resolution (SR), the norm determination is often challenging. This paper proposes
      a method to adaptively determine the optimal norms for both fidelity term and
      regularization term in the (SR) restoration model. Inspired by a generalized
      likelihood ratio test, a piecewise function is proposed to solve the norm of the
      fidelity term. This function can find the stable norm value in a certain number
      of iterations, regardless of whether the noise type is Gaussian, impulse, or
      mixed. For the regularization norm, the main advantage of the proposed method is
      that it is locally adaptive. Specifically, it assigns different norms for
      different pixel locations, according to the local activity measured by a
      structure tensor metric. The proposed method was tested using different types of
      images. The experimental results and error analyses verify the efficacy of the
      method.

PMID- 26208376
TI  - Fuzzy Adaptive Control Design and Discretization for a Class of Nonlinear
      Uncertain Systems.
AB  - In this paper, tracking control problems are investigated for a class of
      uncertain nonlinear systems in lower triangular form. First, a state-feedback
      controller is designed by using adaptive backstepping technique and the universal
      approximation ability of fuzzy logic systems. During the design procedure, a
      developed method with less computation is proposed by constructing one maximum
      adaptive parameter. Furthermore, adaptive controllers with nonsymmetric dead-zone
      are also designed for the systems. Then, a sampled-data control scheme is
      presented to discretize the obtained continuous-time controller by using the
      forward Euler method. It is shown that both proposed continuous and discrete
      controllers can ensure that the system output tracks the target signal with a
      small bounded error and the other closed-loop signals remain bounded. Two
      simulation examples are presented to verify the effectiveness and applicability
      of the proposed new design techniques.

PMID- 26208377
TI  - High-Order Energies for Stereo Segmentation.
AB  - In this paper, we propose a novel segmentation approach for stereo images using
      the high-order energy optimization, which utilizes the disparity maps and
      statistical information of stereo images to enrich the high-order potential
      functions. To the best of our knowledge, our approach is the first one to
      formulate the problem of stereo segmentation as a high-order energy optimization
      problem, which simultaneously segments the foreground objects in left and right
      images using the proposed high-order potential function. A new method for
      designing the penalty function in our high-order term is proposed by the
      corresponding pixels and their neighboring pixels between left and right images.
      The relationships of stereo correspondence by disparity maps are further employed
      to enhance the connections between the left and right stereo images. Experimental
      results demonstrate that the proposed approach can effectively improve the
      performance of two kinds of stereo segmentation, including the automatic saliency
      aware stereocut and the interactive stereo segmentation with user scribbles.

PMID- 26208378
TI  - Effect of Prior Aspirin Treatment on Patients With Acute Coronary Syndromes:
      Insights From the PROSPECT Study.
AB  - BACKGROUND: Prior aspirin treatment is considered a risk factor for adverse
      outcomes in acute coronary syndrome (ACS) patients. The relationships between
      aspirin pretreatment and findings on quantitative coronary angiography (QCA) and
      intravascular ultrasound (IVUS), as well as clinical outcomes, are not well
      understood. METHODS: In the PROSPECT trial, QCA and triple-vessel IVUS imaging
      were performed after successful percutaneous coronary intervention (PCI) of the
      culprit lesion(s) in ACS patients. We compared patients receiving aspirin within
      7 days of enrollment to those naive to aspirin. Propensity score matching was
      performed to adjust for differences in baseline characteristics. RESULTS: Aspirin
      pretreated patients (n = 236; 35%) were older and more likely to have known
      coronary disease than those without pretreatment (P<=.01 for all). Pretreated
      patients had more untreated non-culprit lesions with angiographic and IVUS
      characteristics predictive of future events (53.1% vs 38.6%; P<.001). There were
      no significant differences in overall major adverse cardiac event (MACE) rates at
      3 years between the aspirin and no-aspirin groups (23.6% vs 18.8%, respectively;
      P=.17) in unadjusted or propensity-adjusted analyses. Prior aspirin use was not
      an independent predictor of MACE at 3 years (hazard ratio, 1.21; 95% confidence
      interval, 0.73-2.01; P=.45). CONCLUSION: In the PROSPECT trial, aspirin
      pretreatment identifies an older population with more advanced coronary disease.
      Aspirin pretreatment was not an independent predictor of MACE in ACS patients
      treated with an early invasive strategy. The extent to which aspirin pretreatment
      is a risk factor for adverse events after PCI in ACS should be revisited.

PMID- 26208379
TI  - Lack of Survival Benefit Found With Use of Intraaortic Balloon Pump in
      Extracorporeal Membrane Oxygenation: A Pooled Experience of 1517 Patients.
AB  - OBJECTIVE: Intraaortic balloon pumps (IABPs) are frequently used as an adjunctive
      device to extracorporeal membrane oxygenation (ECMO) and are routinely placed at
      the initiation of ECMO at many institutions. Evidence for the additive benefit of
      IABP therapy is limited and conflicting in part due to small sample sizes. In the
      absence of large randomized trials, a meta-analysis would best elucidate
      potential benefit. METHODS: A systematic PubMed/Medline search was performed.
      Studies reporting on survival to hospital discharge for cardiogenic shock and
      cardiac arrest requiring ECMO with an IABP subgroup were included. Concomitant
      IABP was compared with patients on ECMO alone. Secondary analyses included acute
      myocardial infarction (AMI) and postcardiotomy cardiogenic shock (PCS) subgroups,
      as well as timing of IABP insertion. RESULTS: Sixteen studies were included in
      the main analysis, encompassing 1517 patients. The cumulative survival rate for
      patients on ECMO was 256/683 (37.5%) compared with 294/834 (35.3%) for patients
      with adjunctive IABP. Concomitant IABP was not associated with improved survival
      (risk ratio [RR], 1.143; 95% confidence interval [CI], 0.973-1.343; P=.10). IABP
      was not associated with improved survival in AMI patients (RR, 1.120; 95% CI,
      0.772-1.624; P=.55), PCS (RR, 1.121; 95% CI, 0.826-1.520; P=.46) when placed
      prior to ECMO initiation (RR, 0.948; 95% CI, 0.718-1.252; P=.71), or when
      routinely inserted (RR, 1.102; 95% CI, 0.806-1.506; P=.54). CONCLUSION: Based on
      this observational analysis, the concomitant use of IABP with ECMO did not appear
      associated with a dramatic change in survival outcomes. The routine insertion of
      concomitant IABP with ECMO is not supported by our findings.

PMID- 26208380
TI  - Efficacy and Safety of Transcatheter Aortic Valve Implantation in Aortic Stenosis
      Patients With Extreme Age.
AB  - OBJECTIVES: To investigate the in-hospital and long-term outcomes of patients at
      extreme age with severe symptomatic aortic stenosis (AS) who underwent
      transcatheter aortic valve implantation (TAVI). METHODS: A total of 276
      consecutive patients with a mean age of 82.2 +/- 5.0 years with severe
      symptomatic AS underwent TAVI at our institute. We evaluated periprocedural, in
      hospital, and long-term outcomes in all patients aged >=87 years (the highest
      20th percentile of age distribution) and compared them with the less elderly
      patients. RESULTS: The extremely aged group included 58 patients (21%) >=87 years
      (mean age, 89.0 +/- 1.9 years; 67.2% women). Baseline EuroSCOREs and STS scores
      were 19.6 +/- 11.2% and 9.4 +/- 5.0%, respectively. Nineteen patients (34.5%)
      were considered frail. Following TAVI, all patients regained New York Heart
      Association class 1-2 functional capacity. The main periprocedural and in
      hospital complications were minor vascular complications, bleeding requiring
      blood transfusions, and the need for permanent pacemaker. None of the patients
      suffered from clinical stroke. In comparison to the less elderly patients, there
      were no significant differences in the rates of periprocedural, in-hospital
      complications or long-term survival (log rank, 0.87). CONCLUSIONS: Meticulously
      selected patients at extreme age benefit from TAVI with a reasonable overall
      risk, which does not impact the overall survival or functional status.

PMID- 26208381
TI  - Neonatal diabetes in Ukraine: incidence, genetics, clinical phenotype and
      treatment.
AB  - BACKGROUND: Neonatal diabetes has not been previously studied in Ukraine. We
      investigated the genetic etiology in patients with onset of diabetes during the
      first 9 months of life. METHODS: We established a Pediatric Diabetes Register to
      identify patients diagnosed with diabetes before 9 months of age. Genetic testing
      was undertaken for 42 patients with permanent or transient diabetes diagnosed
      within the first 6 months of life (n=22) or permanent diabetes diagnosed between
      6 and 9 months (n=20). RESULTS: We determined the genetic etiology in 23 of 42
      (55%) patients; 86% of the patients diagnosed before 6 months and 20% diagnosed
      between 6 and 9 months. The incidence of neonatal diabetes in Ukraine was
      calculated to be 1 in 126,397 live births. CONCLUSIONS: Genetic testing for
      patients identified through the Ukrainian Pediatric Diabetes Register identified
      KCNJ11 and ABCC8 mutations as the most common cause (52%) of neonatal diabetes.
      Transfer to sulfonylureas improved glycemic control in all 11 patients.

PMID- 26208382
TI  - Mechanical Strain Affects Some Microrna Profiles in Pre-Oeteoblasts.
AB  - MicroRNAs (miRNAs) are important regulators of cell proliferation,
      differentiation and function. Mechanical strain is an essential factor for
      osteoblast proliferation and differentiation. A previous study revealed that a
      physiological mechanical tensile strain of 2500 microstrain (MUepsilon) at 0.5 Hz
      applied once a day for 1 h over 3 consecutive days promoted osteoblast
      differentiation. However, the mechanoresponsive miRNAs of these osteoblasts were
      not identified. In this study, we applied the same mechanical tensile strain to
      in vitro cultivated mouse MC3T3-E1 pre-osteoblasts and identified the
      mechanoresponsive miRNAs. Using miRNA microarray and qRT-PCR assays, the
      expression patterns of miRNAs were evaluated and 5 of them were found to be
      significantly different between the mechanical loading group and the control
      group: miR-3077-5p, 3090-5p and 3103-5p were significantly upregulated and miR
      466i-3p and 466h-3p were downregulated. Bioinformatics analysis revealed possible
      target genes for these differentially expressed miRNAs. Some target genes
      correlated with osteoblast differentiation. These findings indicated that the
      mechanical strain changed the expression levels of these miRNAs. This might be a
      potential regulator of osteoblast differentiation and responses to mechanical
      strain. 

PMID- 26208383
TI  - Sphingosine-1-Phosphate Induces the Migration and Angiogenesis of Epcs Through
      the Akt Signaling Pathway via Sphingosine-1-Phosphate Receptor 3/Platelet-Derived
      Growth Factor Receptor-beta.
AB  - Endothelial progenitor cells (EPCs) play a fundamental role in neoangiogenesis
      and tumor angiogenesis. Through the sphingosine-1-phosphate receptor 3 (S1PR3),
      sphingosine-1-phosphate (S1P) can stimulate the functional capacity of EPCs.
      Platelet-derived growth factor receptor-beta (PDGFR-beta) contributes to the
      migration and angiogenesis of EPCs. This study aimed to investigate whether S1P
      induces the migration and angiogenesis of EPCs through the S1PR3/PDGFR-beta/Akt
      signaling pathway. We used the Transwell system and the Chemicon In Vitro
      Angiogenesis Assay Kit with CAY10444 (an S1PR3 antagonist), AG1295 (a PDGFR
      kinase inhibitor) and sc-221226 (an Akt inhibitor) to examine the role of the
      S1PR3/PDGFR-beta/Akt pathway in the S1Pinduced migration and angiogenesis of
      EPCs. 

PMID- 26208384
TI  - Bioinformatics-Based Molecular Classification of Arthrobacter Plasmids.
AB  - The omnipresence of Arthrobacter species in polluted and toxic soils indicates
      their great potential in environmental biotechnologies, but practical
      applications of these bacteria are scarce mainly due to the availability of
      useful genetic engineering tools. Although many fully sequenced Arthrobacter
      genomes have been deposited in GenBank, little is known about the biology of
      their plasmids, especially the core functions: replication and partition. In this
      study the available Arthrobacter plasmid sequences were analyzed in order to
      identify their putative replication origin. At least the oris from the cryptic
      plasmids pXZ10142, pCG1, and pBL1 appear to work in this genus. Based on ParA
      homolog sequences, the Arthrobacter specific plasmids were classified into 4
      clades. Iteron-like sequences were identified on most of the plasmids, indicating
      the position of the putative Arthrobacter specific oris. Although attempts were
      made to identify the core gene set required for plasmid replication in this
      genus, it was not possible. The plasmid proteomes showed a rather low similarity.

PMID- 26208385
TI  - Transcriptional profiling of bovine muscle-derived satellite cells during
      differentiation in vitro by high throughput RNA sequencing.
AB  - In this study, we utilized high throughput RNA sequencing to obtain a
      comprehensive gene expression profile of muscle-derived satellite cells (MDSCs)
      upon induction of differentiation. MDSCs were cultured in vitro and RNA was
      extracted for sequencing prior to differentiation (MDSC-P), and again during the
      early and late differentiation (MDSC-D1, and MDSC-D3, respectively) stages.
      Sequence tags were assembled and analyzed by digital gene expression profile to
      screen for differentially expressed genes, Gene Ontology annotation, and pathway
      enrichment analysis. Quantitative real-time PCR was used to confirm the results
      of RNA sequencing. Our results indicate that certain of genes were changed during
      skeletal muscle cell development, cell cycle progression, and cell metabolism
      during differentiation of bovine MDSCs. Furthermore, we identified certain genes
      that could be used as novel candidates for future research of muscle development.
      Additionally, the sequencing results indicated that lipid metabolism might be the
      predominant cellular process that occurs during MDSC differentiation. 

PMID- 26208386
TI  - Inhibition of CEA release from epithelial cells by lipid A of Gram-negative
      bacteria.
AB  - A number of bacterial species, both pathogenic and non-pathogenic, use the human
      CEACAM family members as receptors for internalization into epithelial cells. The
      GPI-linked CEA and CEACAM6 might play a role in the innate immune defense,
      protecting the colon from microbial invasion. Previous studies showed that CEA is
      released from epithelial cells by an endogenous GPI-PLD enzyme. GPI-PLD activity
      was reported to be inhibited by several synthetic and natural forms of lipid A.
      We hypothesized that CEA engagement by Gram-negative bacteria might attenuate CEA
      release from epithelial cells and that this might facilitate bacterial
      colonization. We tested the hypothesis by examining the effect of Escherichia
      coli on CEA release from colorectal cancer cells in a co-culture experiment. A
      subconfluent monolayer culture of colorectal cancer cells (LS-180, Caco-2 and
      HT29/219) was incubated with E. coli. While there was a significant reduction in
      CEA secretion from LS-180 and HT29/219 cells, we found only a small reduction of
      CEA shedding from Caco-2 cells compared to the level from the untreated control
      cells. Furthermore, lipid A treatment of LS-180 cells inhibited CEA release from
      the cells in a dosedependent manner. Western blot analysis of total lysates
      showed that CEA expression levels in cells co-cultured with bacteria did not
      differ from those in untreated control cells. These results suggest that lipid A
      of Gram-negative bacteria might play a role in preventing the release of CEA from
      mucosal surfaces and promote mucosal colonization by bacteria.

PMID- 26208387
TI  - Neurotrophine-3 may contribute to neuronal differentiation of mesenchymal stem
      cells through the activation of the bone morphogenetic protein pathway.
AB  - We investigated whether neurotrophin-3 (NT-3) can promote differentiation of
      mouse bone mesenchymal stem cells (MSCs) into neurons via the bone morphogenetic
      protein pathway. MSCs were prepared from rat bone marrow and either transfected
      with pIRES2-EGFP or pIRES2-EGFP-NT-3 or treated with bone morphogenetic protein
      4. The pIRES2-EGFP-NT-3-transfected MSCs further underwent noggin treatment or
      siRNA-mediated knockout of the TrkC gene or were left untreated.
      Immunofluorescence staining, real-time PCR and Western blot analyses were
      performed to evaluate the transcription and expression of neural-specific genes
      and BMP-Smad signaling. MSCs were efficiently transduced by the NT-3 gene via
      pIRES2-EGFP vectors. pIRES2- EGFP-NT-3 could initiate the transcription and
      expression of neural-specific genes, including nestin, NSE and MAP-2, and
      stimulate BMP-Smad signaling. The transcription and expression of neural-specific
      genes and BMP-Smad signaling were significantly suppressed by siRNA-mediated
      knockdown of the TrkC gene of MSCs. These findings suggest that the BMP signaling
      pathway may be a key regulatory point in NT-3-transfected neuronal
      differentiation of MSCs. The BMP and neurotrophin pathways contribute to a
      tightly regulated signaling network that directs the precise connections between
      neuronal differentiation of MSCs and their targets.

PMID- 26208388
TI  - In vitro and in vivo analysis of human fibroblast reprogramming and multipotency.
AB  - Multipotent stem cells have potential therapeutic roles in the treatment of
      Duchenne muscular dystrophy (DMD). However, the limited access to stem cell
      sources restricts their clinical application. To address this issue, we
      established a simple in vitro epigenetic reprogramming technique in which skin
      fibroblasts are induced to dedifferentiate into multipotent cells. In this study,
      human fibroblasts were isolated from circumcised adult foreskin and were
      reprogrammed by co-culture for 72 h with fish oocyte extract (FOE) in serum-free
      medium. The cells were then observed and analyzed by immunofluorescence staining,
      flow cytometry and in vitro differentiation assays. Then FOE-treated human
      fibroblasts were transplanted by tail vein injection into irradiated mdx mice, an
      animal model of DMD. Two months after injection, the therapeutic effects of FOE
      treated fibroblasts on mdx skeletal muscle were evaluated by serum creatine
      kinase (CK) activity measurements and by immunostaining and RT-PCR of human
      dystrophin expression. The results indicated that the reprogrammed fibroblasts
      expressed higher levels of the pluripotent antigen markers SSEA-4, Nanog and Oct
      4, and were able to differentiate in vitro into adipogenic cells, osteoblastic
      cells, and myotube-like cells. Tail vein injection of FOE-treated fibroblasts
      into irradiated mdx mice slightly reduced serum CK activity and the percentage of
      centrally nucleated myofibers two months after cell transplantation. Furthermore,
      we confirmed human dystrophin protein and mRNA expression in mdx mouse skeletal
      muscle. These data demonstrated that FOE-treated fibroblasts were multipotent and
      could integrate into mdx mouse myofibers through the vasculature. 

PMID- 26208389
TI  - The pharmacological features of bilirubin: the question of the century.
AB  - This review looks at the toxicity and metabolism of bilirubin in terms of its
      pharmacological potential. Its role has gained importance as more research has
      revealed the functional significance and interrelationship between the
      gasotransmitters nitric oxide and carbon monoxide. The biological actions of
      bilirubin have mostly been characterized in the high micromolar range where toxic
      effects occur. However, it could also prove to be an important cytoprotector for
      brain tissue, which is inherently less equipped for antioxidant defense. Plasma
      bilirubin levels negatively correlate to a number of disease states. Higher
      levels of bilirubin that are still within the normal range provide a protective
      effect to the body. The effects on various disorders could be tested using
      controlled pharmacological upregulation of the molecule with animal models. At
      nanomolar concentrations, considerable benefits have been obtained when the
      molecule was delivered pharmacologically under in vitro or in vivo test
      conditions, particularly in neurodegenerative disorders and after tissue or organ
      transplantation. The induction of heme oxygenase-1 (HMOX-1) via the activation of
      nuclear factor erythroid 2-related factor or the use of bile pigments in the
      harvesting of diseased tissue are novel applications, and like every new therapy,
      should be used with caution. HMOX-1 is tissue specific, and in exceptional
      states, such as schizophrenia and specific types of renal disorder, the same
      therapy may have disastrous effects. 

PMID- 26208390
TI  - Evaluation of the expressions pattern of miR-10b, 21, 200c, 373 and 520c to find
      the correlation between epithelial-to-mesenchymal transition and melanoma stem
      cell potential in isolated cancer stem cells.
AB  - Small non-coding RNAs named microRNAs (miRNAs) modulate some functions and
      signaling pathways in skin epithelial cells and melanocytes. They also function
      as oncogenes or tumor suppressors in malignancies and tumor metastasis. We
      investigated the expression patterns of miRNAs, including miR-10b, 21, 200c, 373
      and 520c, which regulate epithelial-to-mesenchymal transition (EMT) and
      metastasis in isolated cancer stem cells (CSCs) and non- CSCs. Six melanoma cell
      lines were tested for the expressions of stem cell markers. Melanoma stem cells
      were enriched via fluorescence-activated cell sorting (FACS) using the CD133 cell
      surface marker or spheroid culture. They were then characterized based on colony
      and sphere formation, and the expressions of stemness and EMT regulator genes and
      their invasion potential were assessed using real-time qRT-PCR and invasion
      assay. Our results indicate that cells enriched via sphere formation expressed
      all the stemness-related genes and had an enhanced number of colonies, spheres
      and invaded cells compared to cells enriched using the CD133 cell surface marker.
      Moreover, miRNAs controlling metastasis increased in the melanospheres. This may
      be related to the involvement of CSCs in the metastatic process. However, this
      must be further confirmed through the application of knockdown experiments. The
      results show that sphere formation is a useful method for enriching melanoma stem
      cells. Melanospheres were found to upregulate miR-10b, 21, 200c, 373 and 520c, so
      we suggest that they may control both metastasis and stemness potential.

PMID- 26208391
TI  - Effects of neuritin on the migration, senescence and proliferation of human bone
      marrow mesenchymal stem cells.
AB  - Neuritin is a neurotrophic factor associated with neuroplasticity. Most studies
      on neuritin focus on the nervous system; however, there has been no comprehensive
      evaluation of neuritin in non-neuronal cells. In this study, we screened 11 cell
      lines and found that neuritin was not expressed in bone marrowderived mesenchymal
      stem cells (BMSCs). Neuritin-expressing BMSCs were obtained by transfection. In
      the neuritin-expressing BMSC model, we observed significantly greater cell
      migration and improved anti-senescence protection, in addition to reduced
      proliferation and viability. In conclusion, neuritin not only plays an important
      role in the nervous system but also has an effect on the migration, senescence,
      proliferation, and viability of stem cells. This study provides a theoretical
      basis for understanding the function of neuritin.

PMID- 26208392
TI  - Lipoxin A4 methyl ester alleviates vascular cognition impairment by regulating
      the expression of proteins related to autophagy and ER stress in the rat
      hippocampus.
AB  - Since autophagy and endoplasmic reticulum stress mechanisms are involved in some
      neurodegenerative and cerebral vascular diseases, we suspected that similar
      mechanisms might participate in vascular cognitive impairments induced by chronic
      cerebral hypoperfusion. Lipoxin A4 methyl ester (LXA4 ME) is an inflammation
      inhibitor that exhibits potent protective effects in experimental stroke models.
      In an earlier study, we found that LXA4 ME improved cognitive deficit in a rat
      model of vascular cognitive impairment created using bilateral common carotid
      artery ligation (BCCAL) and two-vessel occlusion (2VO). In this study, LXA4 ME
      treatment of 2VO rats improved brain morphological defects. We found that LXA4 ME
      reduced the expression of some autophagy- and ERS-related factors in the
      hippocampus of 2VO rats, namely C/EBP homologous protein, beclin1 and the ratio
      of microtubule-associated protein light chain 3 II (LC3-II) to LC3-I. By
      contrast, LXA4 ME upregulated the protein expression of phospho-mTOR, total-mTOR,
      glucose-regulated protein 78 and spliced and unspliced X-box binding protein-1
      mRNA. Differential protein regulation by LXA4 ME might underlie its ability to
      protect cognition after chronic cerebral hypoperfusion. 

PMID- 26208393
TI  - Biomedical and agricultural applications of energy dispersive X-ray spectroscopy
      in electron microscopy.
AB  - Energy dispersive X-ray spectroscopy (EDS) in electron microscopy has been widely
      used in many research areas since it provides precise information on the chemical
      composition of subcellular structures that may be correlated with their high
      resolution images. In EDS the characteristic X-rays typical of each element are
      analyzed and the new detectors - an example of which we describe - allow for
      setting precisely the area of measurements and acquiring signals as a point
      analysis, as a linescan or in the image format of the desired area. Mapping of
      the elements requires stringent methods of sample preparation to prevent
      redistribution/loss of the elements as well as elimination of the risk of
      overlapping spectra. Both qualitative and quantitative analyses may be performed
      at a low probe current suitable for thin biological samples. Descriptions of
      preparation techniques, drawbacks and precautions necessary to obtain reliable
      results are provided, including data on standards, effects of specimen roughness
      and quantification. Data on EPMA application in different fields of biomedical
      and agricultural studies are reviewed. In this review we refer to recent EDS/EPMA
      applications in medical diagnostics, studies on air pollution and agrochemicals
      as well as on plant models used to monitor the environment. 

PMID- 26208394
TI  - Testicular fine-needle aspiration for the assessment of intratesticular hormone
      concentrations.
AB  - Measurement of intratesticular sex steroid concentrations in men informs both the
      development of male hormonal contraceptives and the understanding of male
      infertility. Given the challenges of using invasive techniques to measure
      testicular hormone physiology, our group has used a minimally-invasive fine
      needle aspiration technique to measure intratesticular hormones in normal healthy
      men. Herein, we present a post-hoc analysis of the safety and efficacy of
      testicular fine-needle aspiration (FNA) completed as part of six clinical trials.
      From 2001 through 2011, a total of 404 procedures were conducted among 163
      research volunteers, 85.9% of which were successful in obtaining sufficient fluid
      for the measurement of intratesticular steroid concentrations. Pain was the most
      common side effect, with 36.8% of procedures associated with moderate procedural
      pain and 4.7% with severe procedural pain. Postprocedural pain was uncommon and
      abated within a few days. Mild local bruising occurred with 14.9% of procedures.
      Two serious adverse events (0.5%) required surgical intervention. The risk of an
      adverse event was not associated with age, body mass index, testicular size, or
      the volume of fluid aspirated. Testicular FNA to obtain fluid for measurement of
      intratesticular steroid concentrations frequently causes mild to moderate
      procedural pain, but serious adverse events occur rarely. Testicular FNA has been
      instrumental for defining human intratesticular hormone physiology and is a
      minimally-invasive, safe, effective method for obtaining fluid for research on
      testicular physiology and pathology. 

PMID- 26208396
TI  - Autophagy: a stumbling block of androgen inhibition to treat benign prostatic
      hyperplasia or prostate cancer.

PMID- 26208395
TI  - Active immunization with GnRH-tandem-dimer peptide in young male rats reduces
      serum reproductive hormone concentrations, testicular development and
      spermatogenesis.
AB  - GnRH sterilization vaccines have been developed for various practical and
      clinical reasons. However, conjugation of GnRH peptide to carrier protein has
      many drawbacks, hampering the further commercialization of GnRH vaccines. In this
      study, a new nonconjugated GnRH vaccine, D-Lys6-GnRH-tandem-dimer peptide (TDK),
      emulsified in Specol adjuvant was investigated for its immunocastration efficacy
      in young male rats. Prepubertal male rats were randomly allocated into three
      groups (n = 12): control (no treatment), surgically castrated or immunized
      against 100 MUg TDK in Specol adjuvant at 6 weeks of age (with a booster 8 weeks
      later). Blood samples (for antibody titers and hormone concentrations) were
      collected at 2-week intervals until rats were killed (18 weeks of age). Compared
      to intact controls, active immunization against TDK reduced (P < 0.05) serum
      concentrations of testosterone, inhibin B, LH and FSH, prevented the onset of
      spermatogenesis at puberty. Furthermore, mRNA expressions of GnRH receptor, LH
      beta and FSH-beta in the pituitary, LH receptor, FSH receptor, inhibin alpha,
      betaA and betaB subunit in the testes were decreased in immunocastrated rats
      compared to intact controls (P < 0.05). These results demonstrate for the first
      time that GnRH-tandem-dimer peptide emulsified in Specol is a promising
      veterinary sterilization medicine. 

PMID- 26208397
TI  - Interaction between basigin and monocarboxylate transporter 2 in the mouse testes
      and spermatozoa.
AB  - Basigin is a member of the immunoglobulin superfamily and plays various important
      roles in biological events including spermatogenesis. To examine the basigin
      molecular variants during spermatogenesis and sperm maturation in the mouse,
      immunoprecipitated basigin samples from testis and epididymal spermatozoa were
      analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).
      The results demonstrated that basigin molecules from the testis and spermatozoa
      were separable into two major bands and that the differences in the molecular
      sizes were possibly because of an endoproteolytic cleavage. Since basigin is
      known to be a chaperone for the monocarboxylate transporter 1 (MCT1), the
      localization of basigin, MCT1 and MCT2 was examined during postnatal testicular
      development. Immunohistochemical studies showed different expression patterns of
      MCT1 and MCT2. MCT1 was localized on the surface of spermatogonia, spermatocytes,
      and spermatids. In contrast, MCT2 appeared on the principal piece of spermatozoa
      in the testis, where basigin was also observed. In mature epididymal spermatozoa,
      MCT2 was located on the midpiece, where basigin co-localized with MCT2 but not
      with MCT1. Furthermore, MCT2 was immunoprecipitated with basigin in mouse testes
      and sperm. These results suggest that basigin has a functional role as a binding
      partner with MCT2 in testicular and epididymal spermatozoa. 

PMID- 26208398
TI  - Epididymal research one generation on.

PMID- 26208399
TI  - Looking both ways: new research on old theories.

PMID- 26208400
TI  - Interacting partners of macrophage-secreted cathepsin B contribute to HIV-induced
      neuronal apoptosis.
AB  - OBJECTIVE: HIV-1 infection of macrophages increases cathepsin B secretion and
      induces neuronal apoptosis, but the molecular mechanism remains unclear. DESIGN:
      We identified macrophage-secreted cathepsin B protein interactions
      extracellularly and their contribution to neuronal death in vitro. METHODS:
      Cathepsin B was immunoprecipitated from monocyte-derived macrophage supernatants
      after 12 days postinfection. The cathepsin B interactome was identified by label
      free tandem mass spectrometry and compared with uninfected supernatants. Proteins
      identified were validated by western blot. Neurons were exposed to macrophage
      conditioned media in presence or absence of antibodies against cathepsin B and
      interacting proteins. Apoptosis was measured using TUNEL labeling.
      Immunohistochemistry of postmortem brain tissue samples from healthy, HIV
      infected and Alzheimer's disease patients was performed to observe the ex-vivo
      expression of the proteins identified. RESULTS: Nine proteins co
      immunoprecipitated differentially with cathepsin B between uninfected and HIV
      infected macrophages. Serum amyloid P component (SAPC)-cathepsin B interaction
      increased in HIV-infected macrophage supernatants, while matrix metalloprotease 9
      (MMP-9)-cathepsin B interaction decreased. Pre-treatment of HIV-infected
      macrophage-conditioned media with antibodies against cathepsin B and SAPC
      decreased neuronal apoptosis. The addition of MMP-9 antibodies was not neuro
      protective SAPC was overexpressed in postmortem brain tissue from HIV-positive
      neurocognitive impaired patients compared with HIV positive with normal cognition
      and healthy controls, although MMP-9 expression was similar in all tissues.
      CONCLUSION: Inhibiting SAPC-cathepsin B interaction protects against HIV-induced
      neuronal death and may help to find alternative treatments for HIV-associated
      neurocognitive disorders.

PMID- 26208402
TI  - Victimization in childhood: General and specific associations with physical
      health problems in young adulthood.
AB  - OBJECTIVE: The goal of the current study was to examine the direct relationship
      between diverse types of childhood victimization and physical health problems in
      early adulthood, controlling for other common factors that contribute to physical
      health problems, including psychopathology and health risk behaviors. The
      associations between types of victimization (e.g., physical assault) and specific
      health problems (e.g., pain) were also examined. METHODS: 2500 Swedish young
      adults reported on their exposure to victimization in childhood and their current
      mental and physical health as adults. RESULTS: Using multiple regression, results
      indicated that the amount of childhood victimization was a significant predictor
      of health problems in adulthood, controlling for the significant negative effects
      of health risk behaviors and mental health problems on physical health. Logistic
      regressions indicated that physical assaults and sexual abuse were associated
      with all types of health problems assessed. Sleep problems were associated with
      almost all types of victimization history. CONCLUSIONS: The long-term effects of
      childhood victimization on physical health in adulthood are serious and warrant
      significant attention. Primary care providers should include assessments of past
      victimization as one way of screening for health risk. Health providers should
      also consider multiple points of intervention that may help to reduce physical
      illness. For example, providing a mental health intervention or social service
      support related to victimization experiences may not only address these
      difficulties, but also more broadly impact physical health as well.

PMID- 26208401
TI  - Sparing bilateral neck level IB in oropharyngeal carcinoma and xerostomia
      outcomes.
AB  - OBJECTIVES: To assess whether sparing neck-level IB in target delineation of node
      positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes
      without compromising locoregional control (LRC). METHODS: A total of 125 N+ OPC
      patients with a median age of 57 years underwent chemoradiation between May 2010
      and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16%
      N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other.
      Patients were divided into those who had target delineation sparing of bilateral
      level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of
      contralateral high-level II nodes was also performed more consistently in the
      spared cohort. A prospective xerostomia questionnaire (patient reported) was
      given at each patient follow-up visit to this cohort of patients to assess late
      xerostomia. Clinical assessment (observer rated) at each patient follow-up visit
      was also recorded. RESULTS: The 2-year LRC for the spared and treated cohorts was
      97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional
      failures occurred outside of treatment fields. The spared cohort experienced
      significant benefits in patient-reported xerostomia summary scores (P=0.021) and
      observer-rated xerostomia scores (P=0.006). In addition, there were significant
      reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5
      Gy; P<0.001), contralateral submandibular gland (45.0 vs. 56.2 Gy; P<0.001), oral
      cavity (35.9 vs. 45.2 Gy; P<0.001), and contralateral parotid gland (20.0 vs.
      24.4 Gy; P<0.001). CONCLUSIONS: Target delineation sparing of bilateral level IB
      nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC.
      Patients with reduced target volumes had better patient-reported xerostomia
      outcomes.

PMID- 26208403
TI  - Anxiety, depression and timing of insulin treatment among people with type 2
      diabetes: Nine-year follow-up of the Nord-Trondelag Health Study, Norway.
AB  - BACKGROUND: Depression and anxiety have been found to be predictors of poor
      health outcomes in diabetes, but mechanisms are still unclear. AIMS: To examine
      whether symptoms of anxiety and depression were associated with timing of
      initiating insulin therapy. METHODS: A cohort study of insulin-naive particpants
      with type 2 dabetes completed the Hospital Anxiey and Depression Scale, HADS-A (n
      = 731) and/or the HADS-D (n = 768) in the communy-based Nord-Trondelag Health
      Study (1995-1997). Information on insulin initiation was retrieved from the
      Norwegian Prescription Database from January 1, 2004 to November 21, 2012. Cox
      regression analyses were used to estimate the association between symptoms of
      anxiety, depression and time to insulin initiation. RESULTS: At baseline, 19%
      reported anxiety symptoms (score>=8) and 18% depressive symptoms (score>=8).
      After a mean follow-up of 4.4 (SD 3.6) years, 337 (40%) participants had started
      insulin therapy. After adjustment for sociodemographic and clinical variables,
      anxiety symptoms were associated with later initiation of insulin therapy (HR
      0.70, 95% CI 0.49-0.99), while depressive symptoms were not. Considering groups
      simultaneously, having both elevated depressive and elevated anxiety symptoms was
      associated with later time to insulin initiation (HR 0.62, 95% CI 0.39-0.99),
      while having only anxiety symptoms (without depressive) HR 0.81, 95% CI 0.50
      1.32) or only depressive symptoms (without anxiety) (HR 1.08, 95% CI 0.68-1.72)
      were not. CONCLUSIONS: Anxiety was associated with a later initiation of insulin,
      while depressive symptoms were not. Persons with both elevated levels of anxiety
      and depression were also less likely to start insulin therapy. These results need
      further testing in other prospective studies.

PMID- 26208405
TI  - Improving Patient Care Through Inspiring Happiness.

PMID- 26208404
TI  - Retrospective cues based on object features improve visual working memory
      performance in older adults.
AB  - Research with younger adults has shown that retrospective cues can be used to
      orient top-down attention toward relevant items in working memory. We examined
      whether older adults could take advantage of these cues to improve memory
      performance. Younger and older adults were presented with visual arrays of five
      colored shapes; during maintenance, participants were presented either with an
      informative cue based on an object feature (here, object shape or color) that
      would be probed, or with an uninformative, neutral cue. Although older adults
      were less accurate overall, both age groups benefited from the presentation of an
      informative, feature-based cue relative to a neutral cue. Surprisingly, we also
      observed differences in the effectiveness of shape versus color cues and their
      effects upon post-cue memory load. These results suggest that older adults can
      use top-down attention to remove irrelevant items from visual working memory,
      provided that task-relevant features function as cues. 

PMID- 26208406
TI  - Radiologist Productivity Increases With Real-Time Monitoring: The Hawthorne
      Effect.

PMID- 26208407
TI  - Perspectives of a Young Emergency Radiology Attending.

PMID- 26208408
TI  - A First for Molepolole, Botswana: A Radiology Presence.

PMID- 26208409
TI  - Health markers in obese adolescents improved by a 12-week recreational soccer
      program: a randomised controlled trial.
AB  - The effects of a recreational soccer program (RSP) upon body composition, heart
      rate variability (HRV), biochemical markers, cardio-respiratory fitness, and
      endothelial function in obese adolescents were investigated. A randomised
      controlled clinical trial was conducted with 30 adolescents aged 12-17 years and
      body mass index (BMI) >2 standard deviations of WHO reference values, which were
      assigned to RSP (n = 10, 2 girls) and obese control (n = 10, 4 girls) groups. The
      12-week RSP included 60-min sessions performed 3 times/week. BMI, waist
      circumference, blood pressure, blood glucose, lipid profile, insulin, C-reactive
      protein, HRV, and maximal oxygen consumption (VO2peak) were evaluated following
      standardised procedures. Body composition was determined by dual-energy X-ray
      absorptiometry and endothelial function by venous occlusion plethysmography.
      After intervention, RSP exhibited significant reductions in BMI (-0.7 +/- 0.2 kg
      . m(-2)), waist circumference (-8.2 +/- 1.4 cm), %body fat (-2.2 +/- 0.4%),
      systolic blood pressure (-5.0 +/- 2.3 mmHg), total cholesterol (-16.2 +/- 5.8 mg
      . dL(-1)), triglycerides (-20.5 +/- 12.9 mg . dL(-1)), C-reactive protein (-0.06
      +/- 0.01 mg . dL(-1)), insulin resistance (HOMA-IR, -1.4 +/- 0.6), and
      sympathetic activity (LF, -13.9 +/- 6.6 un) vs. controls (P < 0.05). Significant
      increase was observed in parasympathetic activity (HF, 13.9 +/- 6.6 un), VO2peak
      (7.9 +/- 2.8 ml . kg(-1) . min(-1)), and high-density lipoprotein cholesterol
      (11.0 +/- 6.3 mg . dL(-1)) (P < 0.05). Vascular conductance (19.5 +/- 8.1 ml .
      min(-1) . 100 ml, P = 0.005) increased and vascular resistance (-5.9 +/- 2.4 ml .
      min(-1) . 100 ml, P = 0.041) decreased in RSP, but not in controls. A 12-week
      recreational soccer intervention was effective to improve biochemical,
      cardiovascular, and fitness health markers in obese adolescents.

PMID- 26208410
TI  - Management of Type 2 Late Sleeve Leak by Laparoscopic Suturing and Conversion to
      Roux-en-Y Gastric Bypass: Video Report.
AB  - BACKGROUND: Laparoscopic sleeve forming gastrectomy (SFG) is a commonly performed
      bariatric procedure for the surgical management of morbid obesity. Staple line
      gastric leaks occur infrequently but are the most feared complication causing
      prolonged morbidity (Burgos et al., Obes Surg 19(12):1672-7, 2009; Marquez et
      al., Obes Surg 20(9):1306-11, 2010). Roux-en-Y diversion is an accepted
      management (Baltasar et al., Surg Obes Relat Dis 4(6):759-63, 2008). The aim of
      this video was to demonstrate the operative management of a late sleeve leak by
      laparoscopic suturing & conversion to a RYGB. METHODS: We present the case of an
      18-year-old woman with a BMI of 44.68 kg/m(2) with hypothyroidism and polycystic
      ovarian disease who underwent laparoscopic sleeve gastrectomy and presented with
      a leak on postoperative day 13. She was diagnosed to have a type 2, late leak
      just beyond the esophagogastric junction (Csendes et al., Hepatogastroenterology
      37 Suppl 2:174-7, 1990) RESULTS: In this multimedia high-definition video, we
      present step-by-step the operative management of a late sleeve leak by
      laparoscopic suturing and conversion to a RYGB. Procedure included mobilization
      of the gastric sleeve, identification and suturing of the fistulous opening,
      creation of a gastric pouch, creation of an ante-colic Roux limb, gastrojejunal
      anastomosis and jejuno-jejunal anastomosis. Drainage of fistula gradually
      decreased with absence of a leak on imaging in 12 days. This patient was
      diagnosed with a gastric sleeve leak on the 13th postoperative day, and the time
      to fistula closure from diagnosis was 1 month. CONCLUSIONS: Sleeve leak fistula
      repair with conversion to a RYGB aids healing by providing surgical decompression
      and better drainage. It may be considered as an alternative management technique
      in sleeve leaks.

PMID- 26208411
TI  - Adherence to Psychiatric Follow-up Predicts 1-Year BMI Loss in Gastric Bypass
      Surgery Patients.
AB  - OBJECTIVE: The objective of this study was to investigate the effects of
      adherence to postoperative recommended psychiatric follow-up on weight loss in
      morbid obesity patients with psychiatric disorders 1 year after gastric bypass.
      METHODS: Three hundred eighteen morbidly obese patients were retrospectively
      reviewed. They were divided into four groups according to preoperative
      psychiatric evaluations and adherence to psychiatric follow-up 1 year after their
      bypass surgery. The first group included patients who did not meet the referral
      criteria (NMRC). The second group consisted of patients who did not meet the
      psychiatric diagnostic criteria (NMDC). The third group was patients who met
      criteria for a psychiatric disorder and were nonadherent (NA) to psychiatric
      follow-up. The fourth group consisted of patients who met criteria for a
      psychiatric disorder and were adherent (A) to psychiatric follow-up. RESULTS: The
      A group exhibited higher % change in BMI than the NA and NMRC groups at 1 year
      after bypass surgery. Regression analyses to examine the effects of the grouping
      variable on % change in BMI were performed by controlling the effects of age,
      gender, educational level, and preoperative BMI. The regression coefficient for
      the grouping variable was 0.175 (p = .003) at the 6-month and 0.133 (p = .027) at
      the 1-year % change in BMI. CONCLUSION: Our preliminary data suggest that
      adherence to postoperative psychiatric follow-up is associated with greater
      postoperative weight loss. However, evidence from studies with a longer follow-up
      is required to justify this therapeutic approach.

PMID- 26208412
TI  - Tailored prolapse surgery for the treatment of hemorrhoids with a new dedicated
      device: TST Starr plus.
AB  - PURPOSE: The aim of the study was to assess the results of the stapled transanal
      procedure in the treatment of hemorrhoidal prolapse in terms of postoperative
      complications and recurrence rate using a new dedicated device, TST Starr plus.
      METHODS: Patients affected by III-IV degree hemorrhoidal prolapsed that underwent
      stapled transanal resection with the TST Starr plus were included in the present
      study. Results of the procedure with perioperative complications, postoperative
      complications, and recurrence rate were reported. RESULTS: From November 2012 to
      October 2014, 52 patients (19 females) were enrolled in the study. The main
      symptoms were prolapse (100 %) and bleeding (28.8 %). Transanal rectal resection
      was performed with parachute technique in 24 patients (46.2 %) and purse string
      technique in 23 patients (53.8 %). A mild hematoma at the suture line occurred in
      one patient (1.9 %). Postoperative bleeding was reported in three patients (5.7
      %), in one of which, reoperation was necessary (1.9 %). Tenesmus occurred in one
      patient (1.9 %), and it was resolved with medical therapy. Urgency was reported
      in nine patients (17.1 %) at 7 days after surgery. Of these, three patients (5.7
      %) complained urgency at the median follow-up of 14.5 months. Reoperation was
      performed in one patient (1.9 %) for chronic anal pain for rigid suture fixed on
      the deep plans. Occasional bleeding was reported in four patients (7.7 %). No
      recurrence of prolapse was reported at a median of 14.5 months after surgery,
      even if one patient (1.9 %) had a partial recurrent prolapse of a downstaged
      single pile. CONCLUSIONS: TST Starr plus seems to be safe and effective for a
      tailored transanal stapled surgery for the treatment of III-IV degree
      hemorrhoidal prolapse. The new conformation and innovative technology of the
      stapler seems to reduce some postoperative complications and recurrence rate.

PMID- 26208413
TI  - Diagnostic Ophthalmic Ultrasound for Radiologists.
AB  - Ophthalmic ultrasound is an invaluable tool that provides quick and noninvasive
      evaluation of the eye and the orbit. It not only allows the clinicians to view
      structures that may not be visible with routine ophthalmic equipment or
      neuroimaging techniques but also provides unique diagnostic information in
      various ophthalmic conditions. In this article, the basic principles of
      ophthalmic ultrasound and examination techniques are discussed. Its clinical
      application is illustrated through a variety of ocular pathologic abnormalities
      (eg, narrow angles, ciliary body tumor, detached retina, choroidal melanoma, and
      papilledema). 

PMID- 26208414
TI  - Optical Coherence Tomography for the Radiologist.
AB  - Optical coherence tomography is an imaging technique using low coherence light
      sources to produce high-resolution cross-sectional images. This article reviews
      pertinent anatomy and various pathologies causing optic atrophy (eg, compressive,
      infiltrating, demyelinating) versus optic nerve swelling (from increased
      intracranial pressure known as papilledema or other optic nerve intrinsic
      pathologies). On optical coherence tomography, optic atrophy is often associated
      with reduced average retinal nerve fiber layer thickness, whereas optic nerve
      swelling is usually associated with increased average retinal nerve fiber layer
      thickness. 

PMID- 26208415
TI  - Advanced MR Imaging of the Visual Pathway.
AB  - Vision is one of our most vital senses, deriving from the eyes as well as
      structures deep within the intracranial compartment. MR imaging, through its wide
      selection of sequences, offers an array of structural and functional imaging
      tools to interrogate this intricate system. This review describes several
      advanced MR imaging sequences and explores their potential clinical applications
      as well as areas for further development. 

PMID- 26208416
TI  - Imaging of Optic Neuropathy and Chiasmal Syndromes.
AB  - Optic neuropathy involves loss of visual acuity, color vision, and visual field
      defect with a swollen, pale, anomalous, or normal optic disc seen on fundoscopy.
      Chiasmal disorders classically present with gradual onset of vision loss,
      bitemporal hemianopsia, and occasionally, endocrinopathy if the pituitary gland
      and/or hypothalamus are the causes or are involved. Advance in neuroimaging,
      especially magnetic resonance (MR) imaging, can reveal pathologic conditions
      previously detected only clinically. Some entities have imaging characteristics,
      leading to appropriate treatment without requiring tissue biopsies. Imaging also
      provides disease surveillance and posttreatment assessment, with computed
      tomography and MR imaging being complementary to each other. 

PMID- 26208417
TI  - Imaging of Retrochiasmal and Higher Cortical Visual Disorders.
AB  - Retrochiasmal visual pathways include optic tracts, lateral geniculate nuclei,
      optic radiations, and striate cortex (V1). Homonymous hemianopsia and field
      defect variants with relatively normal visual acuity suggest that the lesions
      involve retrochiasmal pathways. From V1, visual input is projected to higher
      visual association areas that are responsible for perception of objects, faces,
      colors, and orientation. Visual association areas are classified into ventral and
      dorsal pathways. Damage to the ventral stream results in visual object agnosia,
      prosopagnosia, and achromatopsia. Balint syndrome, visual inattention, and pure
      alexia are examples of dorsal stream disorders. Posterior cortical atrophy can
      involve ventral and dorsal streams, often preceding dementia. 

PMID- 26208418
TI  - Imaging of Ocular Motor Pathway.
AB  - Eye movement is controlled by ocular motor pathways that encompass supranuclear,
      nuclear, and infranuclear levels. Lesions affecting certain locations may produce
      localizing signs that help radiologists focus on specific anatomic regions. Some
      pathologic conditions, such as aneurysms and meningiomas, have unique imaging
      characteristics that may preclude unnecessary tissue biopsies. Some conditions
      are life threatening and require urgent or emergent imaging. MR imaging is the
      imaging of choice in evaluation of ocular motor palsy, with magnetic resonance
      angiography or computed tomography angiography indicated in cases of suspected
      aneurysms or neurovascular conflicts. 

PMID- 26208419
TI  - Imaging of Orbital Trauma and Emergent Non-traumatic Conditions.
AB  - Diagnostic imaging has become critical in the care of patients suffering from
      traumatic or nontraumatic emergent orbital conditions. Multidetector computed
      tomography (MDCT) has become the standard imaging modality for assessing orbital
      trauma because of its accurate assessment of orbital skeletal and soft tissues
      injuries. Contrast-enhanced MR imaging is the first-line examination in the
      assessment of nontraumatic orbital conditions given its excellent evaluation of
      the orbital soft tissues. Conventional angiography is necessary in some vascular
      orbital complications and allows for endovascular treatment. This article
      discusses the spectrum of orbital pathology encountered in the imaging of orbital
      trauma and nontraumatic orbital emergencies. 

PMID- 26208420
TI  - Imaging of the Postoperative Orbit.
AB  - Imaging evaluation of the postoperative orbit remains challenging even for the
      expert neuroradiologist. This article provides a simplified framework for
      understanding the complex postoperative appearances of the orbit, in an attempt
      to enhance the diagnostic accuracy of postoperative computed tomography and MR
      imaging of the orbit. Readers are familiarized with the normal appearances of
      common eye procedures and orbit reconstructions to help avoid interpretative
      pitfalls. Also reviewed are imaging features of common surgical complications,
      and evaluation of residual/recurrent neoplasm in the setting of oncologic imaging
      surveillance. 

PMID- 26208421
TI  - Imaging of Pediatric Orbital Diseases.
AB  - This article reviews a variety of congenital and developmental disorders of the
      pediatric orbit with particular emphasis on ocular lesions, followed by a
      description of developmental and neoplastic orbital and ocular masses. The
      relationship of these diseases to various syndromes and/or known genetic
      mutations is also highlighted. 

PMID- 26208423
TI  - Orbit and Neuro-ophthalmic Imaging.

PMID- 26208424
TI  - Improving emergency department throughput: An outcomes evaluation of two
      additional models of care.
AB  - OBJECTIVE: The aim of this study was to explore the impact of incorporating a
      physician at triage (PAT) and the implementation of a medical assessment unit
      (MAU) on emergency department (ED) patient throughput. METHODS: A retrospective
      comparative analysis of two additional models of care (standard care, T1; PAT, T2
      and PATplusMAU, T3) was undertaken. Patient presentations to a large public
      teaching hospital in South-East Queensland between 10th January 2013 and 25th
      February 2013, and the same time period in 2012, were included. The impact of
      these care models on ED length of stay and other outcomes (time to be seen by a
      clinician, time from bed request to ward transfer, meeting 4 hour transit
      targets, admission rates and the proportion of patients who did not wait) were
      compared. RESULTS: Compared to standard care, ED length of stay appeared to
      decrease with the introduction of both models, but was only significantly
      decreased after PATplusMAU was implemented (2013; T1, 186 min; T2, 181 min; T3,
      175 min: T1 vs T3, P < 0.001). Outcomes that improved included: time to be seen
      by a clinician, proportion of patients who did not wait; increase in meeting 4
      hour length of stay target for both admitted and not-admitted patients.
      CONCLUSION: Placing a physician at triage and implementing a medical assessment
      unit were viable models of care that promoted patient flow and helped meet
      several time-sensitive health service targets.

PMID- 26208425
TI  - Nanocarriers with tunable surface properties to unblock bottlenecks in systemic
      drug and gene delivery.
AB  - Nanocarrier-mediated drug and gene delivery systems hold great promise for
      providing more refined delivery (especially in cancer treatments) to maximize
      therapeutic efficacy while minimizing unfavorable side effects. Despite their
      promise, the highly effective transport of therapeutics in vivo remains a
      challenge. Over the last 20years, there has been a large amount of research
      directed toward the development of a multitude of nanocarriers for drug and gene
      delivery, but only a very small part has progressed into clinical trials. This
      suggests that the properties of current nanocarriers are not yet ideal for
      effective drug and gene delivery in vivo. Nanocarrier-mediated drug and gene
      delivery is a multi-step process, and inefficient delivery at any stage would
      ultimately result in an unsuccessful delivery. Unfortunately, existing
      nanocarriers with fixed surface properties, such as a PEGylated, cationized and
      bioconjugated surface, are not versatile enough to overcome the extracellular and
      intracellular barriers which require different surface properties. Consequently,
      their delivery efficacy is not optimal, leading to doubts and debates on the
      value of nanocarrier-based product development. To resolve the "fixed surface
      dilemma", the switchable surfaces of nanocarriers, which can surmount both
      extracellular and intracellular barriers, open up the possibility of highly
      efficient delivery in vivo. Here, we review and highlight the recent developments
      in the design of nanocarrier delivery systems with tunable surface properties in
      response to microenvironment triggers. Strategies including zwitterionic
      nanocarriers, polymer brushes, layer-by-layer nanocarriers and cleavable
      conjugated nanocarriers are presented. These representative examples and their
      respective outcomes elaborate the benefits and efficiencies of these nanocarriers
      at the individual stages of drug and gene delivery. 

PMID- 26208426
TI  - Ultraviolet light-mediated drug delivery: Principles, applications, and
      challenges.
AB  - UV light has been extensively employed in drug delivery because of its
      versatility, ease of manipulation, and ability to induce chemical changes on the
      therapeutic carrier. Here we review the mechanisms by which UV light affects drug
      delivery systems. We will present the challenges facing UV-induced drug delivery
      and some of the proposed solutions. 

PMID- 26208427
TI  - Reduced-Item Food Audits Based on the Nutrition Environment Measures Surveys.
AB  - INTRODUCTION: The community food environment may contribute to obesity by
      influencing food choice. Store and restaurant audits are increasingly common
      methods for assessing food environments, but are time consuming and costly. A
      valid, reliable brief measurement tool is needed. The purpose of this study was
      to develop and validate reduced-item food environment audit tools for stores and
      restaurants. METHODS: Nutrition Environment Measures Surveys for stores (NEMS-S)
      and restaurants (NEMS-R) were completed in 820 stores and 1,795 restaurants in
      West Virginia, San Diego, and Seattle. Data mining techniques (correlation-based
      feature selection and linear regression) were used to identify survey items
      highly correlated to total survey scores and produce reduced-item audit tools
      that were subsequently validated against full NEMS surveys. Regression
      coefficients were used as weights that were applied to reduced-item tool items to
      generate comparable scores to full NEMS surveys. Data were collected and analyzed
      in 2008-2013. RESULTS: The reduced-item tools included eight items for grocery,
      ten for convenience, seven for variety, and five for other stores; and 16 items
      for sit-down, 14 for fast casual, 19 for fast food, and 13 for specialty
      restaurants-10% of the full NEMS-S and 25% of the full NEMS-R. There were no
      significant differences in median scores for varying types of retail food outlets
      when compared to the full survey scores. Median in-store audit time was reduced
      25%-50%. CONCLUSIONS: Reduced-item audit tools can reduce the burden and
      complexity of large-scale or repeated assessments of the retail food environment
      without compromising measurement quality.

PMID- 26208428
TI  - Can self-report instruments of shoulder function capture functional differences
      in older adults with and without a rotator cuff tear?
AB  - Rotator cuff tears (RCT) are prevalent in older individuals and may compound age
      associated functional declines. Our purpose was to determine whether self-report
      measures of perceived functional ability are valid for older patients with RCT.
      Twenty five subjects participated (12M/13F; age=63.9+/-3.0years); 13 with RCT and
      12 controls (CON). Participants completed self-report measures of shoulder
      function (SST, ASES, WORC) and health-related quality of life (SF-36). Isometric
      joint moment and range of motion (ROM) were measured at the shoulder.
      Relationships among functional self-reports, and between these measures and joint
      moment and ROM were assessed; group differences for total and subcategory scores
      were evaluated. There were significant correlations among self-reports (rs=0.62
      0.71, p?0.02). For RCT subjects, ASES was associated with all joint moments
      except adduction (p?0.02); SST, ASES, and WORC were associated with abduction and
      external rotation ROM (p?0.04). For RCT subjects, SST and WORC were associated
      with SF-36 physical function subcategory scores (p?0.05). The RCT group scored
      worse than CON on all functional self-reports (p<0.01) and WORC and ASES
      subcategories (p<0.01). In conclusion, SST, ASES, and WORC demonstrate utility
      and discriminant validity for older individuals by distinguishing those with RCT,
      but this work suggests prioritizing ASES given its stronger association with
      functional group strength. 

PMID- 26208429
TI  - Adaptations to isolated shoulder fatigue during simulated repetitive work. Part
      I: Fatigue.
AB  - Upper extremity muscle fatigue is challenging to identify during industrial tasks
      and places changing demands on the shoulder complex that are not fully
      understood. The purpose of this investigation was to examine adaptation
      strategies in response to isolated anterior deltoid muscle fatigue while
      performing simulated repetitive work. Participants completed two blocks of
      simulated repetitive work separated by an anterior deltoid fatigue protocol; the
      first block had 20 work cycles and the post-fatigue block had 60 cycles. Each
      work cycle was 60s in duration and included 4 tasks: handle pull, cap rotation,
      drill press and handle push. Surface EMG of 14 muscles and upper body kinematics
      were recorded. Immediately following fatigue, glenohumeral flexion strength was
      reduced, rating of perceived exertion scores increased and signs of muscle
      fatigue (increased EMG amplitude, decreased EMG frequency) were present in
      anterior and posterior deltoids, latissimus dorsi and serratus anterior. Along
      with other kinematic and muscle activity changes, scapular reorientation occurred
      in all of the simulated tasks and generally served to increase the width of the
      subacromial space. These findings suggest that immediately following fatigue
      people adapt by repositioning joints to maintain task performance and may also
      prioritize maintaining subacromial space width. 

PMID- 26208430
TI  - Comparison of the bending performance of solid and cannulated spinal pedicle
      screws using finite element analyses and biomechanical tests.
AB  - Spinal pedicle screw fixations have been used extensively to treat fracture,
      tumor, infection, or degeneration of the spine. Cannulated spinal pedicle screws
      with bone cement augmentation might be a useful method to ameliorate screw
      loosening. However, cannulated spinal pedicle screws might also increase the risk
      of screw breakage. Thus, the purpose of this study was to investigate the bending
      performance of different spinal pedicle screws with either solid design or
      cannulated design. Three-dimensional finite element models, which consisted of
      the spinal pedicle screw and the screw's hosting material, were first
      constructed. Next, monotonic and cyclic cantilever bending tests were both
      applied to validate the results of the finite element analyses. Finally, both the
      numerical and experimental approaches were evaluated and compared. The results
      indicated that the cylindrical spinal pedicle screws with a cannulated design had
      significantly poorer bending performance. In addition, conical spinal pedicle
      screws maintained the original bending performance, whether they were solid or of
      cannulated design. This study may provide useful recommendations to orthopedic
      surgeons before surgery, and it may also provide design rationales to
      biomechanical engineers during the development of spinal pedicle screws. 

PMID- 26208431
TI  - Temozolomide competes for P-glycoprotein and contributes to chemoresistance in
      glioblastoma cells.
AB  - Chemotherapeutic resistance can occur by P-glycoprotein (P-gp), a 12
      transmembrane ATP-dependent drug efflux pump. Glioblastoma (GBM) has poor
      survival rate and uniformly acquired chemoresistance to its frontline agent,
      Temozolomide (TMZ). Despite much effort, overcoming TMZ resistance remains a
      challenge. We reported on autonomous induction of TMZ resistance by increased
      transcription MDR1, the gene for P-gp. This study investigated how P-gp and TMZ
      interact to gain resistance. Using an experimental model of Adriamycin-resistant
      DC3F cells (DC3F/Adx), we showed that increased P-gp caused TMZ resistance.
      Increasing concentrations of TMZ competed with Calcein for P-gp, resulting in
      reduced efflux in the DC3F/Adx cells. Three different inhibitors of P-gp reversed
      the resistance to TMZ in two different GBM cell lines, by increasing active
      Caspase 3. Molecular modeling predicted the binding sites to be the intracellular
      region of P-gp and also identified specific amino acids and kinetics of energy
      for the efflux of TMZ. Taken together, we confirmed P-gp targeting of TMZ, a
      crucial regulator of TMZ resistance in GBM. This study provides insights on the
      effectiveness by which TMZ competes with other P-gp substrates, thereby opening
      the door for combined targeted therapies. 

PMID- 26208432
TI  - mTOR inhibitors counteract tamoxifen-induced activation of breast cancer stem
      cells.
AB  - Breast cancer cells with stem cell characteristics (CSC) are a distinct cell
      population with phenotypic similarities to mammary stem cells. CSCs are important
      drivers of tumorigenesis and the metastatic process. Tamoxifen is the most widely
      used hormonal therapy for estrogen receptor (ER) positive cancers. In our study,
      tamoxifen was effective in reducing proliferation of ER + adherent cancer cells,
      but not their CSC population. We isolated, expanded and incubated CSC from seven
      breast cancers with or without tamoxifen. By genome-wide transcriptional analysis
      we identified tamoxifen-induced transcriptional pathways associated with
      ribosomal biogenesis and mRNA translation, both regulated by the mTOR-pathway. We
      observed induction of the key mTOR downstream targets S6K1, S6RP and 4E-BP1 in
      patient derived CSCs by tamoxifen on protein level. Using the mTOR inhibitors
      rapamycin, everolimus and PF-04691502 (a dual PI3K/mTOR inhibitor) and in
      combination with tamoxifen, significant reduction in mammosphere formation was
      observed. Hence, we suggest that the CSC population play a significant role
      during endocrine resistance through activity of the mTOR pathway. In addition,
      tamoxifen further stimulates the mTOR-pathway but can be antagonized using mTOR
      inhibitors. 

PMID- 26208434
TI  - Commentary on 'thirty day outcomes and costs of fenestrated and branched stent
      grafts versus open repair for complex aortic aneurysms': an innovative but
      expensive tool requiring further evaluation.

PMID- 26208433
TI  - Simultaneous suppression of the MAP kinase and NF-kappaB pathways provides a
      robust therapeutic potential for thyroid cancer.
AB  - The MAP kinase and NF-kappaB signaling pathways play an important role in thyroid
      cancer tumorigenesis. We aimed to examine the therapeutic potential of dually
      targeting the two pathways using AZD6244 and Bortezomib in combination. We
      evaluated their effects on cell proliferation, cell-cycle progression, apoptosis,
      cell migration assay, and the activation of the MAPK pathway in vitro and the in
      vivo using tumor size and immunohistochemical changes of Ki67 and ppRB. We found
      inhibition of cell growth rate by 10%, 20%, and 56% (p <0.05), migration to 55%,
      61%, and 29% (p <0.05), and induction of apoptosis to 10%, 15%, and 38% (p <0.05)
      with AZD6244, Bortezomib, or combination, respectively. Induction of cell cycle
      arrest occurred only with drug combination. Dual drug treatment in the xenograft
      model caused a 94% reduction in tumor size (p <0.05) versus 15% with AZD6244 and
      34% with Bortezomib (p < 0.05) and also reduced proliferative marker Ki67, and
      increased pRb dephosphorylation. Our results demonstrate a robust therapeutic
      potential of combining AZD6244 and Bortezomib as an effective strategy to
      overcome drug resistance encountered in monotherapy in the treatment of thyroid
      cancer, strongly supporting clinical trials to further test this strategy. 

PMID- 26208435
TI  - Association of inhibin-alpha gene polymorphisms with follicular cysts in large
      white sows.
AB  - Ovarian follicular cysts are anovulatory follicular structures that have been
      identified in sows and are known to cause infertility. The pathogenesis of
      follicular cysts remains poorly understood. Hormones play key roles in the
      formation and persistence of cysts. The hormone inhibin is a member of the TGF
      beta superfamily and is named for its negative regulation of FSH, another hormone
      that controls follicular recruitment and growth. In the present study, 48 sows
      with follicular cysts and 60 normal sows with no cysts were screened for
      mutations in the inhibin-alpha gene to examine the association of inhibin-alpha
      gene polymorphisms with the presence of follicular cysts. The results show that
      the c.-42G>A and c.3222G>A polymorphisms are significantly associated with
      follicular cysts and that sows with c.-42GG and c.3222GG genotypes have lower
      risk of developing cysts. Our findings may provide novel biological biomarkers
      and promising gene therapy candidates for follicular cyst formation in sows,
      which would greatly benefit pig breeding programs. 

PMID- 26208436
TI  - Motility and fertility of rabbit sperm cryopreserved using soybean lecithin as an
      alternative to egg yolk.
AB  - This study was conducted to investigate whether soy lecithin can be used as an
      alternative cryoprotectant to establish a procedure that does not require the use
      of egg yolk to cryopreserve rabbit strains. Semen from Japanese White rabbits was
      frozen with HEPES extender containing 20% egg yolk (EYH), 0.5% (Lec-0.5), 1.5%
      (Lec-1.5), 2.5% (Lec-2.5), or 3.5% (Lec-3.5; wt/vol) lecithin (type IV-S, >=30%),
      and the motility of thawed sperm was analyzed. The sperm motility in the Lec-1.5
      group was significantly higher than that in the Lec-2.5 and 3.5 groups and
      equivalent to the EYH group. From 17 rounds of artificial insemination with
      frozen-thawed sperm in the EYH and Lec-1.5 groups, 12 rabbits in both groups were
      pregnant (70.6%) and delivered offspring. The litter size was 3.3 in the EYH
      group and 5.1 in the Lec-1.5 group. These results indicate that soy lecithin can
      be used as a substitute for egg yolk as a cryoprotectant on the basis of motility
      and fertility of the frozen-thawed rabbit sperm and that 1.5% lecithin (type IV
      S, >=30%) in the semen extender was the optimum concentration for rabbit sperm
      cryopreservation.

PMID- 26208437
TI  - Prevalence and Incidence of Exudative Age-Related Macular Degeneration in South
      Korea: A Nationwide Population-Based Study.
AB  - PURPOSE: To determine the prevalence and incidence of exudative age-related
      macular degeneration (AMD) in South Korea. DESIGN: Nationwide population-based
      retrospective study using data from the Korean national health claims database
      from 2008 through 2012. PARTICIPANTS: Entire South Korean population 40 years of
      age or older (n = 22,376,510). METHODS: We accessed the national health claims
      database to identify exudative AMD patients using the registration program
      database for rare intractable diseases, which included ophthalmologist-confirmed
      exudative AMD, for copayment reduction. MAIN OUTCOME MEASURES: Prevalence and
      incidence rates of exudative AMD. RESULTS: During the 5-year study period, 81 513
      patients had exudative AMD (48.2% men) and were included in the prevalence
      estimates. The prevalence in the general population 40 years of age or older was
      36.43 (95% confidence interval [CI], 36.18-36.68) per 10,000 people, that in men
      was 37.01 (95% CI, 36.65-37.38) per 10,000 people, and that in women was 35.90
      (95% CI, 35.56-36.24) per 10,000 people. After excluding prevalent cases during
      the initial 2-year washout period, 20,196 cases were identified with incident
      exudative AMD during the final 3-year study period (2010-2012). The incidence in
      the general population 40 years of age or older was 3.02 (95% CI, 2.98-3.06) per
      10,000 person-years, that in men was 3.76 (95% CI, 3.69-3.83) per 10,000 person
      years, and that in women was 2.34 (95% CI, 2.29-2.39) per 10,000 person-years.
      The prevalence and incidence increased with advancing age and peaked at
      approximately 80 years of age. Both the prevalence and incidence were higher in
      men than in women in all age groups. CONCLUSIONS: These detailed estimates of the
      nationwide, population-based prevalence and incidence of exudative AMD in an
      Asian population may help to understand the disease pathophysiology and to plan
      accordingly within the healthcare system.

PMID- 26208438
TI  - Small-Scale Assays for Studying Dissolution of Pharmaceutical Cocrystals for Oral
      Administration.
AB  - The purpose of this study was to better understand the dissolution properties and
      precipitation behavior of pharmaceutical cocrystals of poorly soluble drugs for
      the potential for oral administration based on a small-scale dissolution assay.
      Carbamazepine and indomethacin cocrystals with saccharin and nicotinamide as
      coformers were prepared with the sonic slurry method. Dissolution of the poorly
      soluble drugs indomethacin and carbamazepine and their cocrystals was studied
      with a small-scale dissolution assay installed on a SiriusT3 instrument. Two
      methodologies were used: (i) surface dissolution of pressed tablet (3 mm) in 20
      mL running for fixed times at four pH stages (pH 1.8, pH 3.9, pH 5.4, pH 7.3) and
      (ii) powder dissolution (2.6 mg) in 2 mL at a constant pH (pH 2). Improved
      dissolution and useful insights into precipitation kinetics of poorly soluble
      compounds from the cocrystal form can be revealed by the small-scale dissolution
      assay. A clear difference in dissolution/precipitation behaviour can be observed
      based on the characteristics of the coformer used.

PMID- 26208439
TI  - Nanostructured Cubosomes in a Thermoresponsive Depot System: An Alternative
      Approach for the Controlled Delivery of Docetaxel.
AB  - The aim of the present study was to develop and evaluate a thermoresponsive depot
      system comprising of docetaxel-loaded cubosomes. The cubosomes were dispersed
      within a thermoreversible gelling system for controlled drug delivery. The
      cubosome dispersion was prepared by dilution method, followed by homogenization
      using glyceryl monooleate, ethanol and Pluronic(r) F127 in distilled water. The
      cubosome dispersion was then incorporated into a gelling system prepared with
      Pluronic(r) F127 and Pluronic(r) F68 in various ratios to formulate a
      thermoresponsive depot system. The thermoresponsive depot formulations undergo a
      thermoreversible gelation process i.e., they exists as free flowing liquids at
      room temperature, and transforms into gels at higher temperatures e.g., body
      temperature, to form a stable depot in aqueous environment. The mean particle
      size of the cubosomes in the dispersion prepared with Pluronic(r) F127, with and
      without the drug was found to be 170 and 280 nm, respectively. The prepared
      thermoresponsive depot system was evaluated by assessing various parameters like
      time for gelation, injectability, gel erosion, and in-vitro drug release. The
      drug-release studies of the cubosome dispersion before incorporation into the
      gelling system revealed that a majority (~97%) of the drug was released within 12
      h. This formulation also showed a short lag time (~3 min). However, when
      incorporated into a thermoresponsive depot system, the formulation exhibited an
      initial burst release of ~21%, and released only ~39% drug over a period of 12 h,
      thus indicating its potential as a controlled drug delivery system.

PMID- 26208440
TI  - Damage threshold in adult rabbit eyes after scleral cross-linking by
      riboflavin/blue light application.
AB  - Several scleral cross-linking (SXL) methods were suggested to increase the
      biomechanical stiffness of scleral tissue and therefore, to inhibit axial eye
      elongation in progressive myopia. In addition to scleral cross-linking and
      biomechanical effects caused by riboflavin and light irradiation such a treatment
      might induce tissue damage, dependent on the light intensity used. Therefore, we
      characterized the damage threshold and mechanical stiffening effect in rabbit
      eyes after application of riboflavin combined with various blue light
      intensities. Adult pigmented and albino rabbits were treated with riboflavin (0.5
      %) and varying blue light (450 +/- 50 nm) dosages from 18 to 780 J/cm(2) (15 to
      650 mW/cm(2) for 20 min). Scleral, choroidal and retinal tissue alterations were
      detected by means of light microscopy, electron microscopy and
      immunohistochemistry. Biomechanical changes were measured by shear rheology. Blue
      light dosages of 480 J/cm(2) (400 mW/cm(2)) and beyond induced pathological
      changes in ocular tissues; the damage threshold was defined by the light
      intensities which induced cellular degeneration and/or massive collagen structure
      changes. At such high dosages, we observed alterations of the collagen structure
      in scleral tissue, as well as pigment aggregation, internal hemorrhages, and
      collapsed blood vessels. Additionally, photoreceptor degenerations associated
      with microglia activation and macroglia cell reactivity in the retina were
      detected. These pathological alterations were locally restricted to the treated
      areas. Pigmentation of rabbit eyes did not change the damage threshold after a
      treatment with riboflavin and blue light but seems to influence the vulnerability
      for blue light irradiations. Increased biomechanical stiffness of scleral tissue
      could be achieved with blue light intensities below the characterized damage
      threshold. We conclude that riboflavin and blue light application increased the
      biomechanical stiffness of scleral tissue at blue light energy levels below the
      damage threshold. Therefore, applied blue light intensities below the
      characterized damage threshold might define a therapeutic blue light tolerance
      range. 

PMID- 26208441
TI  - Functional Comparison of 45 Naturally Occurring Isoforms of the Plasmodium
      falciparum Chloroquine Resistance Transporter (PfCRT).
AB  - At least 53 distinct isoforms of Plasmodium falciparum chloroquine resistance
      transporter (PfCRT) protein are expressed in strains or isolates of P. falciparum
      malarial parasites from around the globe. These parasites exhibit a range of
      sensitivities to chloroquine (CQ) and other drugs. Mutant PfCRT is believed to
      confer cytostatic CQ resistance (CQR(CS)) by transporting CQ away from its DV
      target (free heme released upon hemoglobin digestion). One theory is that
      variable CQ transport catalyzed by these different PfCRT isoforms is responsible
      for the range of CQ sensitivities now found for P. falciparum. Alternatively,
      additional mutations in drug-selected parasites, or additional functions of
      PfCRT, might complement PfCRT-mediated CQ transport in conferring the range of
      observed resistance phenotypes. To distinguish between these possibilities, we
      recently optimized a convenient method for measuring PfCRT-mediated CQ transport,
      involving heterologous expression in Saccharomyces cerevisiae. Here, we use this
      method to quantify drug transport activity for 45 of 53 of the naturally
      occurring PfCRT isoforms. Data show that variable levels of CQR likely depend
      upon either additional PfCRT functions or additional genetic events, including
      perhaps changes that influence DV membrane potential. The data also suggest that
      the common K76T PfCRT mutation that is often used to distinguish a P. falciparum
      CQR phenotype is not, in and of itself, a fully reliable indicator of CQR status.

PMID- 26208442
TI  - Rheumatoid arthritis in Latin America: the importance of an early diagnosis.
AB  - The generalization of the early rheumatoid arthritis (ERA) concept and the
      existence of a window of therapeutic opportunity-a time span in which the
      institution of a proper therapeutic method for the disease would determine
      clinical improvement-have set the notion that early diagnosis and treatment may
      modify the course of the disease. Although in several regions of the world,
      especially in North America and Europe, since the year 2000, a significant
      reduction in diagnostic delay was observed in cohorts of patients with rheumatoid
      arthritis (RA), probably reflecting a stronger awareness of the importance of
      early diagnosis, this is not a reality in Latin America (LA). LA is a region of
      great economic inequality, with disparities in access to the public healthcare
      system and limited access to private medicine, being widely difficult to obtain a
      specialized medical evaluation in both scenarios. This paper aims to briefly
      review the main difficulties in the management of ERA in LA, based on the review
      of the literature, on the evaluation of a survey conducted among 214
      rheumatologists of LA, members of Pan-American League of Associations for
      Rheumatology (PANLAR) and the experience of the authors. The paper also aims to
      propose solutions to the difficulties in managing ERA in LA.

PMID- 26208443
TI  - From the model of integral attention to the creation of centers of excellence in
      rheumatoid arthritis.
AB  - For the Pan American Health Organization (PAHO), the care of patients with
      chronic diseases currently experiences fragmentation in attention, generating
      poor performance of health services. Thus, comprehensive health care strategies
      arise to mitigate these problems; one of them are Centers of Excellence (CoEs),
      which aim to obtain high quality results in health from the adequate and minimum
      use of resources. The objective of this study was to describe the history and
      current context of the CoE in comprehensive care in patients with rheumatoid
      arthritis (RA). A systematic search of the literature terms (MeSH) was performed.
      The bases used were PubMed, Ebsco Host, Lilacs, Science Direct, Ovid, and Google
      (gray literature). The source of the information was evaluated to determine its
      quality. International standards focus the CoEs starting from comprehensive
      management of patients with RA and patient volume, continuous improvement, and
      quality of health care, constituting an interdisciplinary team. The REAL-PANLAR
      group suggested that the inclusion of the strategy "Treat to Target", and patient
      education improves patient conditions and understanding of the disease. RA is a
      prevalent and costly disease. The creation of comprehensive care centers of the
      CoE type is an initiative that improves the prognosis of RA. This document aims
      to encourage rheumatologists and scientific societies to structure CoE in an
      interdisciplinary endeavor.

PMID- 26208444
TI  - Idiopathic retroperitoneal fibrosis: clinicopathologic features and outcome
      analysis.
AB  - To describe clinical features and outcomes of 26 patients with idiopathic
      retroperitoneal fibrosis from a single center, we reviewed medical records of
      consecutive patients with idiopathic retroperitoneal fibrosis evaluated at our
      facility from January 1, 1998 to December 31, 2013 for clinical features,
      laboratory and radiographic findings, management, and outcomes. Twenty-six
      patients met criteria for idiopathic retroperitoneal fibrosis and were included
      in the study. Median age at diagnosis was 58 years; male-female ratio was
      3.3:1.0. Median duration of symptoms was 7 weeks. Abdominal, flank, and/or low
      back pain were the most common presenting symptoms. Four patients (15 %) had
      associated autoimmune or fibrosing disorders. Baseline erythrocyte sedimentation
      rate was elevated in 17 (77 %) of 22 patients tested and C-reactive protein was
      elevated in 10 (56 %) of 18 patients tested. Hydronephrosis was present in 17 (68
      %) patients; 8 (47 %) of 17 had bilateral hydronephrosis. Retroperitoneal mass
      biopsy was performed in 18 (69 %) patients. Two patients had idiopathic
      retroperitoneal fibrosis classifiable as IgG4-related disease. Therapy consisted
      of medications alone in 7 cases, surgical interventions alone in 7 cases, and a
      combination in 11 cases. One patient achieved remission with no treatment. Most
      patients treated medically received initial corticosteroids. Methotrexate (1
      case), azathioprine (1 case), mycophenolate mofetil (1 case), and tamoxifen (5
      cases) were used. No relapses occurred after a median 5-year follow-up. Two (8 %)
      patients died; five (19 %) developed cancer after diagnosis. In this series, we
      emphasize the importance of early diagnosis and therapy for overall favorable
      prognosis of idiopathic retroperitoneal fibrosis.

PMID- 26208445
TI  - The Effectiveness of Tyrosine Kinase Inhibitors and Molecular Monitoring Patterns
      in Newly Diagnosed Patients With Chronic Myeloid Leukemia in the Community
      Setting.
AB  - BACKGROUND: Clinical outcomes of patients with chronic myeloid leukemia (CML)
      treated in clinical trials, including response to therapy, may not be
      representative of those treated in a community setting. Thus, we sought to
      determine the real-world effectiveness of first-line tyrosine kinase inhibitors
      in CML by evaluating response rates, all-cause discontinuation, and adherence.
      Response monitoring patterns were also analyzed. PATIENTS AND METHODS: This
      retrospective observational study, using the McKesson Specialty Health/US
      Oncology Network (MSH/USON) iKnowMed electronic health record database and
      medical charts, identified newly diagnosed CML patients who received first-line
      imatinib, dasatinib, or nilotinib from July 2007 to March 2011, and were then
      followed for >= 18 months. RESULTS: Three hundred patients met study criteria
      (222 imatinib-treated, 34 dasatinib-treated, and 44 nilotinib-treated in the
      first-line). Molecular and cytogenetic response assessments were conducted less
      frequently than recommended (40% never had cytogenetic or molecular monitoring at
      any time). Patients treated with either dasatinib or nilotinib experienced higher
      response rates by 6, 12, and 18 months, faster time to major molecular response,
      and a significantly lower rate of all-cause treatment discontinuation within 18
      months relative to imatinib-treated patients. Approximately 56% of all patients
      were adherent to tyrosine kinase inhibitor therapy. CONCLUSION: Dasatinib and
      nilotinib were more effective than imatinib as first-line therapy for CML in a
      community setting, as observed in descriptive and univariate analyses. The
      frequency of cytogenetic and molecular monitoring was lower than that recommended
      by current guidelines, including patients with no molecular or cytogenetic
      assessments during the 18-month follow-up. Therefore, MSH/USON is working toward
      improving compliance with response monitoring guidelines.

PMID- 26208446
TI  - Cushing's syndrome is associated with sleep alterations detected by wrist
      actigraphy.
AB  - BACKGROUND: The association between the hypothalamic-pituitary-adrenal (HPA) axis
      and sleep is well described. It is also known that HPA axis disturbances have an
      effect on sleep. In fact, patients affected by Cushing's syndrome (CS) often
      complain about poor sleep quality. Our aim was to evaluate objective sleep
      quality and duration in patients with Cushing's syndrome in active phase, using
      wrist actigraphy. PATIENTS AND METHODS: In 12 patients with active CS without
      ongoing specific therapy (11 F, 1 M; age 40.0 +/- 10.9 years; BMI 28.4 +/- 6.7
      kg/m(2)) and 12 healthy control subjects (HS) (11 F, 1 M; age 44.0 +/- 11.0
      years; BMI 23.9 +/- 4.2 kg/m(2)) an actigraphic evaluation was performed on 3
      consecutive days under free living conditions. Objective measurement of sleep
      duration and quality was estimated by an actiwatch, which is a wristwatch-like
      device used to detect motor activity. RESULTS: In CS patients, wrist actigraphy
      showed higher fragmented sleep (fragmentation index CS 16.2 +/- 4.2, HS 13.0 +/-
      3.6; p = 0.034) and increased nocturnal motor activity (total activity score CS
      8318 +/- 4308, HS 4971 +/- 2372; p = 0.020; mean activity score CS 8.7 +/- 4.2,
      HS 5.4 +/- 2.2; p = 0.030; mean score in active time CS 104.8 +/- 39.2, HS 74.8
      +/- 23.1; p = 0.030). On the contrary, actual sleep time resulted similar in CS
      and HS. No correlation was found between sleep alterations and urinary free
      cortisol in patients. CONCLUSIONS: The impaired actigraphic parameters described
      in our study suggest that hypercortisolism is associated with sleep alterations,
      which could contribute to the worsening of life quality and metabolic
      comorbidities associated with CS. These results have to be confirmed in a larger
      cohort of patients, using more accurate instruments for sleep assessment.

PMID- 26208447
TI  - Reproductive desires of men and women living with HIV: implications for family
      planning counselling.
AB  - The reproductive desires of people living with HIV/AIDS (PLHIV) of low
      socioeconomic standing attending public health facilities in South Africa were
      studied. HIV-positive men, pregnant and non-pregnant women were recruited from
      two clinics at a large public hospital in Tshwane, South Africa. Individual
      interviews were used to explore the reproductive desires of HIV-positive
      participants. HIV counsellors' perceptions of their clients' reproductive desires
      were explored during focus group discussions. Parenthood proved to be an
      important factor to all participants in continuation of the family and
      establishing their gender identities, despite the possible risk of HIV
      transmission and community stigmatization. Different cultural procreation rules
      for men and women and stigmatizing attitudes towards PLHIV affected their
      reproductive decision making. Women had the dilemma of choosing which community
      expectations they wanted to fulfil. Community stigmatization towards PLHIV was
      visible in the negative attitudes of some HIV counsellors regarding HIV and
      procreation. Because the reproductive desires of PLHIV are currently not given
      high priority in HIV prevention and family planning in the public health sector
      in South Africa, the prevention of HIV transmission may be jeopardized. These
      results necessitate the integration of HIV and sexual and reproductive health
      counselling on a primary health care level. 

PMID- 26208448
TI  - Investigating the effect of ethnicity on IVF outcome.
AB  - Success rates for IVF among women from different ethnic groups have been
      inconclusive. In this study, the relationship between ethnicity and IVF outcome
      was investigated. Results of a cohort study analysing 13,473 first cycles were
      compared with the results of meta-analysed data from 16 published studies.
      Adjustment was made for age, body-mass index, cause of infertility, duration of
      infertility, previous live birth, previous spontaneous abortion and number of
      embryos transferred. Black and South Asian women were found to have lower live
      birth rates compared with White women: Black versus White (OR 0.42 [0.25 to
      0.70]; P = 0.001); South Asian versus White (OR 0.80 [0.65t o 0.99]; P = 0.04).
      Black women had significantly lower clinical pregnancy rates compared with White
      women (OR 0.41 [0.25 to 9 0.67]; P < 0.001). The meta-analysed results also
      showed that Black and South Asian women had statistically significant reduced
      odds of live birth (OR 0.62 [0.55 to 0.71); P < 0.001 and OR 0.66 [0.52 to 0.85);
      P = 0.001, respectively). Black and South Asian women seem to have the poorest
      outcome, which is not explained by the commonly known confounders. Future
      research needs to investigate the possible explanations for this difference and
      improve IVF outcome for all women. 

PMID- 26208450
TI  - Characterization of two MODY2 mutations with different susceptibility to
      activation.
AB  - Glucokinase plays a key role in glucose sensing in pancreatic beta cells and in
      liver metabolism. Heterozygous inactivating glucokinase mutations cause the
      autosomal dominantly inherited MODY2 subtype of maturity-onset diabetes of the
      young. The goal of this study was to elucidate the pathogenicity of the recently
      described glucokinase mutants L304P and L315H, located in an alpha-helix and
      connecting region, respectively, at the outer region of the large domain of
      glucokinase. Both mutants showed wild-type-like cytosolic localization, but
      faster protein degradation in insulin-secreting MIN6 cells. However, strongly
      reduced nuclear/cytoplasmic localization of the mutants was observed in primary
      hepatocytes suggesting reduced interaction with the liver specific glucokinase
      regulatory protein. Both mutants displayed a significantly lowered glucokinase
      activity compared to the wild-type protein. Even though the L315H protein showed
      the lowest enzymatic activity, this mutant was very sensitive to allosteric
      activation. The endogenous activator fructose-2,6-bisphosphatase evoked an
      increase in glucokinase activity for both mutants, but much stronger for L315H
      compared to L304P. The synthetic activator RO281675 was ineffective against the
      L304P mutant. Expression of the mutant proteins evoked loss of glucose-induced
      insulin secretion in MIN6 cells. Administration of RO281675 increased insulin
      secretion, however, only for the L315H mutant. Thus, a glucokinase activator drug
      therapy may help MODY2 patients not in general, but seems to be a useful strategy
      for carriers of the L315H glucokinase mutation. 

PMID- 26208451
TI  - B-cell-activating factor deficiency attenuates high-fat diet-induced glucose
      intolerance by potentiating adipose tissue function.
AB  - B-cell-activating factor (BAFF) has recently been demonstrated to be expressed in
      adipocytes and up-regulated by high-fat diet feeding, indicating a possible role
      in metabolic regulation. Here we show that glucose tolerance was significantly
      improved in high-fat diet-fed BAFF knockout (BAFF(-/-)) mice. BAFF(-/-) mice
      revealed higher levels of glucose transporter expression and insulin-stimulated
      Akt phosphorylation in brown adipose tissue compared to wild type controls.
      Expression levels of mitochondrial ND5 and genes involved in lipid metabolism
      were significantly elevated in brown adipose tissue of BAFF(-/-) mice, and this
      enhancement was found to be mediated by FGF21 and leptin. It was also observed
      that expression of IL-10 and foxp3 was increased in adipose tissues, as well as
      PPARgamma activity in white adipose tissue. Our findings suggest that suppression
      of BAFF could have a therapeutic potential for prevention of type 2 diabetes. 

PMID- 26208452
TI  - p62 prevents carbonyl cyanide m-chlorophenyl hydrazine (CCCP)-induced apoptotic
      cell death by activating Nrf2.
AB  - Carbonyl cyanide m-chlorophenyl hydrazone (CCCP) is a mitochondrial depolarizing
      agent that induces reactive oxygen species (ROS)-mediated cell death. The Nrf2
      Keap1 pathway is crucial for the elimination of ROS in stressed cells. However,
      the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in
      CCCP-induced cell death is unknown. In this study, we demonstrated that CCCP
      promotes Keap1 degradation, and thereby activates Nrf2. This CCCP-mediated Keap1
      degradation is partly dependent on autophagy. Moreover, CCCP-induced Keap1
      degradation is mainly reliant on p62, which functions as an adaptor protein
      during selective autophagy. Lack of p62 blocked CCCP-induced Keap1 degradation
      and inhibited Nrf2 activation, and thereby increased the accumulation of ROS.
      Ablation of p62 increased the susceptibility of cells to oxidative stress. These
      results indicate that p62 plays an important role in protecting cells against
      oxidative stress through Keap1 degradation-mediated Nrf2 activation. 

PMID- 26208453
TI  - Efficient endodermal induction of human adipose stem cells using various
      concentrations of Activin A for hepatic differentiation.
AB  - Activin A, which is a signaling molecule similar to Nodal, rapidly promotes
      endoderm induction of both embryonic stem (ES) cells and MSCs. Protocols for
      hepatic induction exhibit differences in efficiency and reproducibility depending
      on the specific methods or sources of MSCs. We characterized the effects of
      Activin A concentration on induction efficiency during hepatic differentiation of
      MSCs. Human MSCs (hMSCs) were differentiated into a hepatic lineage via a three
      step protocol. Cells were first cultured in fetal bovine serum-free MSCs
      conditioned medium supplemented with Activin A (20, 50, or 100 ng/mL) for 3 days
      followed by treatment with additional agents. RT-PCR analysis,
      immunocytochemistry assays, periodic acid and Schiff's solution staining, and
      ELISAs were performed to confirm hepatic induction of hMSCs. Expression of genes
      related to the primitive foregut endoderm was observed in cells treated with
      higher concentration of Activin A. Gene expression related to functional
      primitive hepatocytes was observed in the early phases of hepatic
      differentiation. During the early period of the differentiation protocol, greater
      albumin secretion was observed when cells were treated with higher concentrations
      of Activin A. CONCLUSION: Thus, Activin A concentration affects the rate of
      endoderm induction of hMSCs, and at higher concentrations in vitro.

PMID- 26208454
TI  - SIRT1 regulates autophagy and diploidization in parthenogenetic haploid embryonic
      stem cells.
AB  - Recent studies have demonstrated that parthenogenetic haploid embryonic stem
      cells (designated as ph ESCs) was difficult to maintain the haploid status or
      cell viability over time during differentiation or high passages, as undergoing
      readily self-diploidize spontaneously. Here, we found that age-related oxidative
      stress and autophagic cell death in ph ESCs at high passage were close to 1 mM
      H2O2 treatment. Exogenous H2O2 tended to promote SIRT1 expression and induce more
      autophagy through mTOR pathway in control ph ESCs, by contrast more apoptosis via
      activation of p53 and caspase-3 in SIRT1-knockdown ph ESCs. Furthermore, we also
      evaluated that SIRT1 directly decreased p53 expression via increasing H3K9 di-
      and tri-methylation in both nucleus and cytoplasm of ph ESCs, whereas indirectly
      inhibited DNA demethylation and replication through H3K9me2 blocking TET3. In
      summary, the results revealed that the diploidization of ph ESCs at high passage
      might correlate with SIRT1 as an important role in regulating autophagy and TET3
      expression. 

PMID- 26208455
TI  - One-day high-fat diet induces inflammation in the nodose ganglion and
      hypothalamus of mice.
AB  - A high-fat diet (HFD) induces inflammation in systemic organs including the
      hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the
      visceral organs and central nervous system, and the gastric-derived orexigenic
      peptide ghrelin transmits its starvation signals to the hypothalamus via the
      vagal afferent nerve. Here we investigated the inflammatory response in vagal
      afferent neurons and the hypothalamus in mice following one day of HFD feeding.
      This treatment increased the number of macrophages/microglia in the nodose
      ganglion and hypothalamus. Furthermore, one-day HFD induced expression of Toll
      like receptor 4 in the goblet cells of the colon and upregulated mRNA expressions
      of the proinflammatory biomarkers Emr1, Iba1, Il6, and Tnfalpha in the nodose
      ganglion and hypothalamus. Both subcutaneous administration of ghrelin and celiac
      vagotomy reduced HFD-induced inflammation in these tissues. HFD intake triggered
      inflammatory responses in the gut, nodose ganglion, and subsequently in the
      hypothalamus within 24 h. These findings suggest that the vagal afferent nerve
      may transfer gut-derived inflammatory signals to the hypothalamus via the nodose
      ganglion, and that ghrelin may protect against HFD-induced inflammation. 

PMID- 26208456
TI  - Over-expression of TRIM37 promotes cell migration and metastasis in
      hepatocellular carcinoma by activating Wnt/beta-catenin signaling.
AB  - Hepatocellular carcinoma (HCC) is the most common cancer in the world especially
      in East Asia and Africa. Advanced stage, metastasis and frequent relapse are
      responsible for the poor prognosis of HCC. However, the precise mechanisms
      underlying HCC remained unclear. So it is urgent to identify the pathological
      processes and relevant molecules of HCC. TRIM37 is an E3 ligase and has been
      observed deregulated expression in various tumors. Recent studies of TRIM37 have
      implicated that TRIM37 played critical roles in cell proliferation and other
      processes. In the present study, we demonstrated that TRIM37 expression was
      notably up-regulated in HCC samples and was associated with advanced stage and
      tumor volume, which all indicating the poor outcomes. We also found that TRIM37
      could serve as an independent prognostic factor of HCC. During the course of in
      vitro and in vivo work, we showed that TRIM37 promoted HCC cells migration and
      metastasis by inducing EMT. Furthermore, we revealed that the effect of TRIM37
      mediated EMT in HCC cells was achieved by the activation of Wnt/beta-catenin
      signaling. These finding may provide insight into the understanding of TRIM37 as
      a novel critical factor of HCC and a candidate target for HCC treatment. 

PMID- 26208457
TI  - Selective inhibition of TNFR1 reduces osteoclast numbers and is differentiated
      from anti-TNF in a LPS-driven model of inflammatory bone loss.
AB  - The treatment of autoimmune disorders has been revolutionised by the introduction
      of biologics such as anti-tumour necrosis factor (anti-TNF). Although in
      rheumatoid arthritis patients a bone sparing effect of anti-TNF has been shown,
      the mechanism is not fully understood. Anti-TNF molecules block tumour necrosis
      factor (TNF) and prevent signalling via both TNF receptor 1 (TNFR1; p55) and TNF
      receptor 2 (TNFR2; p75). However, signalling via TNFR2 is reported to have
      protective effects in a number of cell and organ systems. Hence we set out to
      investigate if pharmacological inhibition of TNFR1 had differential effects
      compared to pan-TNF inhibition in both an in vitro cell-based model of human
      osteoclast activity and an in vivo mouse model of lipopolysaccharide (LPS)
      induced osteolysis. For the in vitro experiments the anti-human TNFR1 domain
      antibody (dAb) DMS5541 was used, whereas for the in vivo mouse experiments the
      anti-mouse TNFR1 dAb DMS5540 was used. We show that selective blocking of TNFR1
      signalling reduced osteoclast formation in the presence of TNF. Subcutaneous LPS
      injection over the calvaria leads to the development of osteolytic lesions within
      days due to inflammation driven osteoclast formation. In this model, murine TNFR2
      genetically fused with mouse IgG1 Fc domain (mTNFR2.Fc), an anti-TNF, did not
      protect from bone loss in contrast to anti-TNFR1, which significantly reduced
      lesion development, inflammatory infiltrate, and osteoclast number and size.
      These results support further exploring the use of TNFR1-selective inhibition in
      inflammatory bone loss disorders such as osteomyelitis and peri-prosthetic
      aseptic loosening. 

PMID- 26208458
TI  - Low expression of ferroxidases is implicated in the iron retention in human
      atherosclerotic plaques.
AB  - The effect of iron on the progress of atherosclerosis is still controversial. To
      explore the relationship between atherosclerotic plaques and iron metabolism and
      how iron is accumulated in plaque macrophages, we performed Oil red O staining to
      detect the lipid of the atherosclerotic plaques, enzyme-linked immunosorbent
      assay to detect the intracellular lipids (total cholesterol, free cholesterol)
      and serum hepcidin, Western-blot to examine the iron-related proteins,
      immunohistochemical and immunofluorescence assays to localize ferroportin 1 in
      macrophages. The contents of serum iron and transferrin saturation were measured.
      The results confrimed that atherosclerotic plaques were all lipid-rich. Compared
      to normal vessel wall, atherosclerotic plaques had significantly higher levels of
      ferritin and ferroportin 1. Strikingly, we found the much lower levels of
      ferroxidases ceruloplasmin and hephaestin in plaque tissue than the normal
      vessel, while the content of serum hepcidin, iron and transferrin saturation were
      similar in these two groups. The novel finding suggests that the inability of
      ferrous iron to be oxidized into ferric iron might be a potential mechanism for
      iron retention in plaques. 

PMID- 26208459
TI  - Antioxidant activity evaluation by physiologically relevant assays based on
      haemoglobin peroxidase activity and cytochrome c-induced oxidation of liposomes.
AB  - Two new protocols for exploring antioxidant-related chemical composition and
      reactivity are described: one based on a chronometric variation of a haemoglobin
      ascorbate peroxidase assay and one based on cytochrome c-induced oxidation of
      lecithin liposomes. Detailed accounts are given on their design, application,
      critical correlations with established methods and mechanisms. These assays are
      proposed to be physiologically relevant and bring new information regarding a
      real sample, both qualitative and quantitative. The well-known assays used for
      evaluation of antioxidant (re)activity are revisited and compared with these new
      methods. Extracts of the Hedera helix L. are examined as test case, with focus on
      seasonal variation and on leaf, fruit and flower with respect to chromatographic,
      spectroscopic and reactivity properties. According to the set of assays
      performed, winter are the most antioxidant, followed by summer leaves, and then
      by flowers and fruits. 

PMID- 26208460
TI  - Screening for GFAP rearrangements in a cohort of Alexander disease and
      undetermined leukoencephalopathy patients.
AB  - Alexander disease (AxD), a fatal degenerative leukoencephalopathy, is caused by
      de novo heterozygous missense mutations in the Glial Fibrillary Acidic Protein
      (GFAP) gene. The pathological hallmark of the disease is the presence of
      Rosenthal fibers, cytoplasmic inclusions in astrocytes, composed mainly of GFAP,
      alphaB-crystallin and HSP27. To date, several patients with a typical
      presentation of the disease or displaying characteristic Rosenthal fibers in
      brain material have been reported with no GFAP mutation. Recently, several
      studies have demonstrated a correlation between Rosenthal fiber formation and
      wild-type GFAP overexpression, despite the absence of mutations. We tested the
      hypothesis that a GFAP gene rearrangement could modulate AxD severity or promote
      GFAP overexpression and aggregation, resulting in leukoencephalopathy. A QMPSF
      assay was validated for 11 exonic fragments: 3 in control genes (CFTR, DSCR1, F9)
      and 8 corresponding to GFAP exons. A total of 97 patients suspected of AxD were
      analyzed: 28 with a GFAP mutation; 69 with clinical and magnetic resonance
      imaging criteria compatible with the disease. Neither duplications nor deletions
      of GFAP were found, suggesting that GFAP coding-region rearrangements may not be
      involved in AxD or Alexander-related leukoencephalopathies. In addition, 80
      patients with undetermined leukodystrophies, and negative for PLP1, GJA12, Sox10
      and MCT8 mutations and PLP1 and Lamin B1 rearrangements, were tested. These
      patients were also negative for GFAP rearrangements. Other hypotheses should be
      investigated for a molecular diagnosis in patients with undetermined
      leukoencephalopathy: mutations in GFAP isoforms, splicing sites or regulatory
      regions, or defaults in genes encoding molecular partners of GFAP. 

PMID- 26208461
TI  - Unmet needs and depression among carers of people newly diagnosed with cancer.
AB  - AIMS: The aims of this analysis were to examine levels of unmet needs and
      depression among carers of people newly diagnosed with cancer and to identify
      groups who may be at higher risk, by examining relationships with demographic
      characteristics. METHODS: One hundred and fifty dyads of people newly diagnosed
      with cancer and their carers, aged 18 years and older, were recruited from four
      Australian hospitals. People with cancer receiving adjuvant cancer treatment with
      curative intent, were eligible to participate. Carers completed the Supportive
      Care Needs Survey-Partners & Caregivers (SCNS-P&C45), and both carers and
      patients completed the Centre of Epidemiologic-Depression Scale (CES-D). RESULTS:
      Overall, 57% of carers reported at least one, 37% at least three, 31% at least
      five, and 15% at least 10 unmet needs; the most commonly endorsed unmet needs
      were in the domains of information and health care service needs. Thirty percent
      of carers and 36% of patients were at risk of clinical depression. A weak to
      moderate positive relationship was observed between unmet needs and carer
      depression (r=0.30, p<0.001). Carer levels of unmet needs were significantly
      associated with carer age, hospital type, treatment type, cancer type, living
      situation, relationship status (in both uni- and multi-factor analysis); person
      with cancer age and carer level of education (in unifactor analysis only); but
      not with carer gender or patient gender (in both uni- and multi-factor analyses).
      CONCLUSION: Findings highlight the importance of developing tailored programmes
      to systematically assist carers who are supporting patients through the early
      stages of cancer treatment.

PMID- 26208462
TI  - Prior long response to androgen deprivation predicts response to next-generation
      androgen receptor axis targeted drugs in castration resistant prostate cancer.
AB  - BACKGROUND: There is an urgent need for qualified predictive biomarkers of
      sensitivity for the treatments used in patients with castration-resistant
      prostate cancer (CRPC). We attempted to identify ready-to-use clinical predictors
      of improved outcome in metastatic CRPC (mCRPC) patients treated with next
      generation androgen receptor (AR) axis targeted drugs. PATIENTS AND METHODS: We
      reviewed a cohort of patients who received AR axis targeted drugs for CRPC at two
      major French cancer centres. The predictive role of several clinical, biological
      and radiological parameters on progression-free survival (PFS) was studied.
      RESULTS: The study cohort consisted of 173 patients. Median duration of response
      to initial androgen deprivation therapy (ADT) (time to castration resistance,
      TTCRPC) was 17.8 months. The 50% prostate-specific antigen (PSA) response rate to
      AR axis targeted drugs was 16% (95% confidence interval (CI): 6-27) and 41% (95%
      CI: 30-47) in patients with TTCRPC of under and over 12 months respectively
      (p=0.005). Median PFS was 2.8 months (95% CI: 2.1-3.9) and 5.8 (95% CI: 4.6-7.8;
      HR: 0.58, p=0.002). In patients treated with post-docetaxel enzalutamide (n=57),
      median PFS was 2.8 months and 8.6 months, (Hazard ratio (HR)=3.1; 95% CI: 1.6
      5.8, p=0.0016) according to TTCRPC, whereas no difference was observed in placebo
      treated patients (n=27). The 50% PSA response rate to enzalutamide was 8% (95%
      CI: 0-38) and 58% (95% CI: 42-73) in patients with a TTCRPC of under and over 12
      months respectively (p<0.001). CONCLUSION: The previous duration of response to
      ADT is a predictor of sensitivity to next generation AR axis targeted drugs in
      patients with mCRPC.

PMID- 26208463
TI  - [Below 26 gestational week prematurity: What support?].
AB  - Management and decision whether to begin intensive care for very preterm infants
      below 26 WG and at borderline viability remains controversial, and survival rates
      for these children vary greatly and justify discussion with regards to literature
      data and according to the experience of others countries. If active management is
      more difficult with very preterm infants 24-25 WG, mortality is increased
      comparing with newborns of more than 26 WG. This is partly explained by
      limitations of active neonatal intensive care. Nevertheless, neurocomportemental
      and cognitive results are not so unfavorable. This justifies a human, medical,
      and ethical multidiciplinary discussion including the parents' wishes for an
      active resuscitation or a palliative management. Using the only criteria of
      gestational age is not a reliable tool to predict survival and neurodevelopmental
      outcome of preterm infants. It is very important to identify other prenatal
      factors such prenatal corticosteroid administration, gender, fetal estimated
      weight, amniotic fluid and absent/reverse end diastolic flow umbilical doppler.
      Implication and listening the parents' preferences are essential after individual
      information, objective and a honest counseling including mortality, morbidity and
      risks of neurocomportmental impairments. Birth and counseling should be done in
      reference maternofetal center with obstetricians and neonatalogist specialized in
      this topic. A real difficulty is to consider the route of delivery and the
      possibility that caesarean section could improve survival rates. Induction of
      labour is very often a high risk of failure and route of delivery remains
      controversial and this is a real question in order to improve survival rates.
      Literature is poor and conflicting without randomized trials. Caesarean section
      presents maternal risks such as pathologic placentation, haemorrhage delivery and
      increasing risks for the subsequent gestation. So, if it is not a good idea to
      recommend a systematic caesarean delivery, it is not ethical to refuse this route
      of delivery only because of the gestational age even in extremely premature
      birth.

PMID- 26208464
TI  - Efficacy of anthelmintic treatment in captive-reared black stilts (Himantopus
      novaezelandiae) released to the wild.
AB  - AIMS: To assess the efficacy of praziquantel (PZQ) administered to control
      helminths in captive-reared critically endangered black stilts (Himantopus
      novaezelandiae) before their release into the wild and determine the effect on
      their survival shortly after release. METHODS: Of 77 captive black stilts, 37
      were treated with PZQ prior to release into the wild in South Canterbury, New
      Zealand, in August and September 2007. Faecal helminth egg counts (FEC) were
      measured before and after anthelmintic treatment, and before and after release to
      the wild using modified faecal flotation and sedimentation methods. In addition,
      total helminth counts were determined in 11 of the birds that died following
      release, as well as four captive and 11 other wild stilts. RESULTS: The efficacy
      of PZQ against trematodes was 92% and against Capillaria spp. was 34%. No
      trematode or Capillaria spp. eggs were detected in treated birds 1 day after
      treatment, but FEC increased 3-5 days after treatment. There were no differences
      in the total helminth counts for trematodes, cestodes or Capillaria spp. in
      control or treated birds (p>0.2). Survival did not differ between treatment
      groups in the August or September releases (p>0.4). Of control and treated birds,
      11/17 (65%) and 8/14 (57%) survived to 31 days, respectively, in the August
      release, and 16/20 (80%) and 10/15 (67%) survived to 84 days, respectively, in
      the September release. CONCLUSION: Overall, the results suggest that PZQ
      treatment may be an unnecessary cost and the risks of producing anthelmintic
      resistance, injuring the birds during processing or producing an unnecessary
      stress response at the time of release could exceed any likely benefits. CLINICAL
      RELEVANCE: It is recommended that pre-release anthelmintic treatment of black
      stilts should be used only if indicated by health screening. Any treatment should
      incorporate annual efficacy testing to monitor the emergence of anthelmintic
      resistance.

PMID- 26208465
TI  - Salvage liver transplantation after laparoscopic resection for hepatocellular
      carcinoma: a multicenter experience.
AB  - Liver transplantation is the ideal treatment for patients affected by early stage
      hepatocellular carcinoma and chronic liver disease. Considering organs shortage,
      alternative treatments have to be adopted to minimize the waitlist drop-out, and
      in case of recurrence within the accepted criteria, salvage transplantation can
      be considered. Surgical resection is one of the most effective treatments, with
      the possibility of oncological radicality and pathological analysis of the
      specimen. Although these theoretical advantages, surgical strategy cannot be
      applied to all patients because of the impaired liver function as well as the
      amount of parenchyma to be resected does not allow a sufficient future liver
      remnant. Furthermore, resection by laparotomy may lead to strong intra-abdominal
      adhesions in a contest of portal hypertension and, as potential consequence,
      increase transplantation difficulty raising morbidity. Laparoscopic liver
      resection is now performed as a routine procedure in tertiary referral centers,
      with increasing evidence of long-term results comparable to traditional surgery
      together with the advantages of a minimally invasive approach. In addition, with
      a salvage transplantation strategy that has been shown to be comparable to
      primary transplantation, the patient can live with his native liver avoiding an
      invasive procedure and long-term immunosuppression, allowing the use of liver
      grafts for the community. We present the results of an Italian multicenter
      experience of salvage liver transplantation following the recurrence of HCC
      initially treated by laparoscopic resection in 31 patients, performed by four
      referral centers. Mean operative transplantation time was 450 min, morbidity was
      41.9%, 90-days mortality was 3.2%, and median post-operative length of stay was
      17.9 days. Salvage liver transplantation after laparoscopic liver resection for
      HCC is comparable to open surgery in terms of operative time, oncologic
      radicality, morbidity and mortality, with the advantages of laparoscopic surgery.

PMID- 26208466
TI  - The crystal structure of Erwinia amylovora levansucrase provides a snapshot of
      the products of sucrose hydrolysis trapped into the active site.
AB  - Levansucrases are members of the glycoside hydrolase family and catalyse both the
      hydrolysis of the substrate sucrose and the transfer of fructosyl units to
      acceptor molecules. In the presence of sufficient sucrose, this may either lead
      to the production of fructooligosaccharides or fructose polymers. Aim of this
      study is to rationalise the differences in the polymerisation properties of
      bacterial levansucrases and in particular to identify structural features that
      determine different product spectrum in the levansucrase of the Gram-negative
      bacterium Erwinia amylovora (Ea Lsc, EC 2.4.1.10) as compared to Gram-positive
      bacteria such as Bacillus subtilis levansucrase. Ea is an enterobacterial
      pathogen responsible for the Fire Blight disease in rosaceous plants (e.g., apple
      and pear) with considerable interest for the agricultural industry. The crystal
      structure of Ea Lsc was solved at 2.77 A resolution and compared to those of
      other fructosyltransferases from Gram-positive and Gram-negative bacteria. We
      propose the structural features, determining the different reaction products, to
      reside in just a few loops at the rim of the active site funnel. Moreover we
      propose that loop 8 may have a role in product length determination in
      Gluconacetobacter diazotrophicus LsdA and Microbacterium saccharophilum FFase.
      The Ea Lsc structure shows for the first time the products of sucrose hydrolysis
      still bound in the active site.

PMID- 26208467
TI  - The proteomics of wool fibre morphogenesis.
AB  - Gel and gel-free proteomic techniques have been used for the first time to
      directly study the proteins present in whole wool follicles and dissected
      portions of follicles that correlated with morphological changes in the
      developing fibre as determined by transmission electron microscopy. Individual
      wool follicles were dissected into four portions designated as the bulb,
      elongation, keratogenous and keratinisation portions. Gel-free proteomic analysis
      of dissected portions from 30 follicles showed that the first keratins to appear
      were K31, K35 and K85, in the bulb portion. The first epithelial KAP,
      trichohyalin, was detected in the bulb portion and the first cortical KAP,
      KAP11.1 was found in the elongation portion. Other major trichocyte keratins and
      cortical KAPs began to appear further up the follicle in the keratogenous and
      keratinisation zones. These results were consistent with what has been observed
      from gene expression studies and correlated well with the morphological changes
      observed in the follicle. Other proteins detected by this approach included the
      keratin anchor protein desmoplakin, as well as vimentin and epithelial keratins,
      histones, ribosomal proteins and collagens. Two-dimensional electrophoretic (2DE)
      analysis of dissected portions of 50 follicles revealed substantial changes in
      the position, number and intensity of the spots of the trichocyte keratins as
      they progressed through the follicle zones, suggesting that they are subject to
      modification as a result of the keratinisation process. Also present in the 2DE
      maps were a number of epithelial keratins, presumably from the inner and outer
      root sheaths, and the dermal components. 

PMID- 26208468
TI  - The Ku-Mar zinc finger: A segment-swapped zinc ribbon in MarR-like transcription
      regulators related to the Ku bridge.
AB  - Two putative oxidative-stress sensor proteins from Pseudomonas aeruginosa, PA1607
      and PA1374, belong to the MarR family of transcription regulators and possess a
      unique mode of dimerization. In these proteins, in addition to the alpha-helices
      involved in dimerization, inter-subunit contacts are strengthened by additional C
      terminal beta-strands. Using sequence and structure analysis we show that these
      beta-strands constitute a novel segment-swapped zinc ribbon domain. We detect the
      presence of the zinc ribbon domain in MarR proteins from many bacterial homologs.
      While the metal-chelating residues of the zinc ribbons are absent in most members
      of this family, we could however identify several species of Proteobacteria,
      Actinobacteria and Firmicutes that possess intact zinc-chelating sites.
      Conservation pattern of metal-chelating residues together with the extensive
      structural resemblance to zinc ribbons, in particular to the bridge-region of the
      dsDNA break repair protein Ku, suggests that the C-terminal beta-rich region of
      these proteins is a zinc ribbon. Sequence analysis also supports a distant
      evolutionary connection between the zinc ribbons of the MarR and Ku families.
      However, unlike Ku where the segment-swapped zinc ribbons play a role in DNA
      binding and obligate dimerization, their primary role in MarR appears to be in
      dimerization and strengthening of inter-subunit contacts. 

PMID- 26208469
TI  - Population pharmacokinetics and dosing simulations of cefepime in septic shock
      patients receiving continuous renal replacement therapy.
AB  - The aim of this study was to describe the population pharmacokinetics of cefepime
      in septic shock patients requiring continuous renal replacement therapy and to
      determine whether current or alternative dosing regimens can achieve PK/PD
      targets. In this observational PK study, 62 samples from 13 patients were
      analysed using non-linear mixed-effects modelling. Different dosing regimens were
      evaluated using Monte Carlo simulations with ultrafiltration flow rates (UFRs) of
      1000, 1500 and 2000 mL/h. The probability of target attainment was calculated
      against a conservative (60% T(>MIC)) and a higher PK/PD target (100% T(>MIC))
      against an MIC of 8 mg/L, the clinical susceptibility breakpoint for Pseudomonas
      aeruginosa. A one-compartment model with between-subject variability (BSV) on
      clearance and volume of distribution (V(d)) described the data adequately. UFR
      was supported as a covariate on both parameters. Typical values for clearance and
      V(d) were 4.4L/h (BSV 37%) and 40.9L (BSV 20%), respectively. Dosing simulations
      showed failure to achieve both a conservative and a higher PK/PD target using a
      dose of 1g q12h for patients treated with a high UFR (>=1500 mL/h). The dose of
      2g q8h or 1g q6h leads to optimal target attainment for high UFR. One gram q8h is
      optimal for low UFR (<=1000 mL/h). We found important variability in PK
      parameters. Dosing simulations show that a dose of 2g q8h or 1g q6h is needed to
      ensure rapid achievement of adequate levels if the UFR is >=1500 mL/h and 1g q8h
      for low UFR (<=1000 mL/h).

PMID- 26208471
TI  - Genetics of Cushing's disease: an update.
AB  - INTRODUCTION: Cushing's disease (CD) results from uncontrolled hypercortisolism
      induced by ACTH-secreting corticotroph adenomas; accordingly, patients diagnosed
      with CD usually present several comorbidities and an increased risk of mortality.
      Hypothesis-driven screenings have led to identification of rare alterations in a
      low number of patients, although the genetic basis underlying CD has remained
      unclear until recently. Using whole-exome sequencing, recurrent mutations have
      been reported in the gene coding for the ubiquitin-specific protease 8 (USP8), a
      protein with deubiquitinase (DUB) activity that modulates the lysosomal turnover
      of the EGF receptor (EGFR) and other membrane proteins. METHODS: In this review,
      we summarize the recent genetic findings and discuss the clinical and
      pathological implications of USP8 deregulation in corticotroph adenomas.
      CONCLUSIONS: Mutations in USP8 have been identified in 35-62 % of functional
      sporadic corticotroph adenomas causing Cushing's disease, but not in any other
      type of pituitary tumor. These mutations are found mostly in adult female
      patients and lead to an aberrant DUB activation by impairing the regulation of
      USP8 by members of the 14-3-3 family of proteins. The consequence of this
      hyperactivation is a longer retention of EGFR at the plasma membrane which
      promotes an enhanced production of ACTH.

PMID- 26208472
TI  - A novel AVP gene mutation in a Turkish family with neurohypophyseal diabetes
      insipidus.
AB  - PURPOSE: Familial neurohypophyseal diabetes insipidus (FNDI) is a rare, autosomal
      dominant, inherited disorder which is characterized by severe polydipsia and
      polyuria generally presenting in early childhood. In the present study, we aimed
      to analyze the AVP gene in a Turkish family with FNDI. METHODS: Four patients
      with neurohypophyseal diabetes insipidus and ten healthy members of the family
      were studied. Diabetes insipidus was diagnosed by the water deprivation test in
      affected family members. Mutation analysis was performed by sequencing the whole
      coding region of AVP-NPII gene using DNA isolated from peripheral blood samples.
      RESULTS: Urine osmolality was low (<300 mOsm/kg) during water deprivation test,
      and an increase more than 50 % in urine osmolality and recovery of the symptoms
      were observed by the administration of desmopressin in all patients. Plasma
      copeptin levels were lower than expected according to plasma osmolality.
      Pituitary MRI revealed partial empty sella with a bright spot in index patient
      and a normal neurohypophysis in the other affected subjects. Genetic screening
      revealed a novel, heterozygous mutation designated as c.-3A>C in all patients.
      CONCLUSION: c.-3A>C mutation in 5'UTR of AVP gene in this family might lead to
      the truncation of signal peptide, aggregation of AVP in the cytoplasm instead of
      targeting in the endoplasmic reticulum, thereby could disrupt AVP secretion
      without causing neuronal cytotoxicity, which might explain the presence of bright
      spot. The predicted effect of this mutation should be investigated by further in
      vitro molecular studies.

PMID- 26208470
TI  - Regulation of the perilymphatic-endolymphatic water shunt in the cochlea by
      membrane translocation of aquaporin-5.
AB  - Volume homeostasis of the cochlear endolymph depends on radial and longitudinal
      endolymph movements (LEMs). LEMs measured in vivo have been exclusively
      recognized under physiologically challenging conditions, such as experimentally
      induced alterations of perilymph osmolarity or endolymph volume. The regulatory
      mechanisms that adjust LEMs to the physiological requirements of endolymph volume
      homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)
      based "water shunt" during the postnatal development of the mouse cochlea and its
      regulation by different triggers. The final complementary expression pattern of
      AQP5 (apical membrane) and AQP4 (basolateral membrane) in outer sulcus cells
      (OSCs) of the cochlear apex is acquired at the onset of hearing function
      (postnatal day (p)8-p12). In vitro, hyperosmolar perfusion of the perilymphatic
      fluid spaces or the administration of the muscarinic agonist pilocarpine in
      cochlear explants (p14) induced the translocation of AQP5 channel proteins into
      the apical membranes of OSCs. AQP5 membrane translocation was blocked by the
      muscarinic antagonist atropine. The muscarinic M3 acetylcholine (ACh) receptor
      (M3R) was identified in murine OSCs via mRNA expression, immunolabeling, and in
      vitro binding studies using an M3R-specific fluorescent ligand. Finally, the
      water shunt elements AQP4, AQP5, and M3R were also demonstrated in OSCs of the
      human cochlea. The regulation of the AQP4/AQP5 water shunt in OSCs of the
      cochlear apex provides a molecular basis for regulated endolymphatic volume
      homeostasis. Moreover, its dysregulation or disruption may have pathophysiologic
      implications for clinical conditions related to endolymphatic hydrops, such as
      Meniere's disease. 

PMID- 26208473
TI  - Role of nonlinear localized Ca(2+) pulses along microtubules in tuning the
      mechano-sensitivity of hair cells.
AB  - This paper aims to provide an overview of the polyelectrolyte model and the
      current understanding of the creation and propagation of localized pulses of
      positive ions flowing along cellular microtubules. In that context, Ca(2+) ions
      may move freely on the surface of microtubule along the protofilament axis, thus
      leading to signal transport. Special emphasis in this paper is placed on the
      possible role of this mechanism in the function of microtubule based kinocilium,
      a component of vestibular hair cells of the inner ear. We discuss how localized
      pulses of Ca(2+) ions play a crucial role in tuning the activity of dynein
      motors, which are involved in mechano-sensitivity of the kinocilium. A prevailing
      notion holds that the concentration of Ca(2+) ions around the microtubules within
      the kinocilium represents the control parameter for Hopf bifurcation. Therefore,
      a key feature of this mechanism is that the velocities of these Ca(2+) pulses be
      sufficiently high to exert control at acoustic frequencies. 

PMID- 26208474
TI  - Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1
      polarization of macrophages.
AB  - Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but
      the underlying mechanism is unknown. Here, we demonstrated that, in mouse with
      DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1
      macrophages, while Tim-3 downregulation or blockade resulted in an increased M1
      response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis
      and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by
      decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing
      macrophages with intestinal lymphocytes decreased the pro-inflammatory response.
      Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim
      3 blockade failed to exacerbate colitis or increase M1 macrophage response in the
      TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR
      4 downstream transcriptional factor regulating macrophage polarization. A better
      understanding of this pathway may shed new light on colitis pathogenesis and
      result in a new therapeutic strategy. 

PMID- 26208475
TI  - Impact of HER2 codon 655 polymorphism and expression of HER2 and HER3 in non
      small cell lung cancer patients.
AB  - The aim of the study was to assess the expression and significance of HER2 and
      HER3, and Ile/Val single nucleotide polymorphism (SNP) of HER2 in lung cancer
      patients. Thirty seven cases of lung cancer were investigated
      immunohistochemically for HER2 and HER3 expression. PCR followed by restriction
      fragment length polymorphism (RFLP) was used to analyze the presence of HER-2 SNP
      at codon 655 in 20 samples. The results were compared with clinical and
      pathological parameters of investigated patients.We found that 100% of the cases
      were negative for HER2, 29.7% were with moderate or strong HER3 expression and
      70.3% of the tumors-without or with low expression for HER3. Lymph node
      metastasis were found in 40% of HER3 positive cases (chi(2) = 4.752; p = 0.029).
      Moderately-differentiated tumors do not express neither of investigated markers
      (chi(2) = 6.719; p = 0.035). HER2 RFLP-PCR analysis showed genotype AG in five
      patients (25%) and the rest of 15 cases (75%) had AA (Ile/Ile) genotype. Patients
      with metastasis had genotype AA (Ile/Ile) in 80% and genotype AG (Ile/Val) in 20%
      (chi(2) = 2.857; p = 0.091).Our results indicate that SNP in HER2 codon 655 and
      investigation of HER2 and HER3 expression could be helpful to outline the
      prognosis for patients with lung adenocarcinoma.

PMID- 26208476
TI  - Classification of osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is an extremely heterogeneous group of heritable
      connective tissue disorders. Most of the affected patients carry autosomal
      dominant mutations in the genes encoding for collagen type I, the most abundant
      protein of the bone extracellular matrix. The resulting phenotypes are extremely
      broad and have been classified by Sillence and colleagues into four groups
      according to clinical, radiological and genetic criteria.More recently, proteins
      have been described that interact directly or indirectly with collagen
      biosynthesis and their deficiency result in rare forms of mostly autosomal
      recessive OI sharing phenotypic features of 'classical' types but lacking primary
      defects in type I collagen. Consequently the Sillence classification has been
      gradually expanded to include novel forms based on the underlying mutations. The
      goal of this article is to revisit the actual OI classification and to outline
      current approaches in categorizing the disorder. 

PMID- 26208477
TI  - Bone mass and mineralization in osteogenesis imperfecta.
AB  - The main clinical features of osteogenesis imperfecta (OI) are low bone mass and
      high bone fragility. While the decrease in bone mass is generally regarded as an
      indicator of disease severity, bone fragility appears as the hallmark of the
      disorder. Bone has a multiscale hierarchical structural organization and is
      optimized to resist to fractures. In OI, modifications at the molecular level
      affect the total mechanical integrity of the bone. A specific characteristic in
      OI is that the bone matrix is abnormally high mineralized independently of the
      underlying mutation or clinical severity. The increased matrix mineralization
      affects bone material quality, leading to increased stiffness and brittleness and
      making bone prone to fractures. The purpose of this review is to give further
      insights on bone matrix mineralization in OI and to discuss advantages and
      pitfalls of invasive and noninvasive imaging techniques. 

PMID- 26208478
TI  - Combination of antibodies directed against different ErbB3 surface epitopes
      prevents the establishment of resistance to BRAF/MEK inhibitors in melanoma.
AB  - Patients with metastatic melanoma bearing V600 mutations in BRAF oncogene
      clinically benefit from the treatment with BRAF inhibitors alone or in
      combination with MEK inhibitors. However, a limitation to such treatment is the
      occurrence of resistance. Tackling the adaptive changes helping cells survive
      from drug treatment may offer new therapeutic opportunities. Very recently the
      ErbB3 receptor has been shown to act as a central node promoting survival of BRAF
      mutated melanoma. In this paper we first demonstrate that ErbB3/AKT
      hyperphosphorylation occurs in BRAF mutated melanoma cell lines following
      exposure to BRAF and/or MEK inhibitors. This strongly correlates with increased
      transcriptional activation of its ligand neuregulin. Anti-ErbB3 antibodies impair
      the establishment of de novo cell resistance to BRAF inhibition in vitro. In
      order to more potently ablate ErbB3 activity we used a combination of two anti
      ErbB3 antibodies directed against distinct epitopes of its extracellular domain.
      These two antibodies in combo with BRAF/MEK inhibitors potently inhibit in vitro
      cell growth and tumor regrowth after drug withdrawal in an in vivo xenograft
      model. Importantly, residual tumor masses from mice treated by the antibodies and
      BRAF/ERK inhibitors combo are characterized almost exclusively by large necrotic
      areas with limited residual areas of tumor growth. Taken together, our findings
      support the concept that triple therapy directed against BRAF/MEK/ErbB3 may be
      able to provide durable control of BRAF mutated metastatic melanoma. 

PMID- 26208479
TI  - Intracellular lactate-mediated induction of estrogen receptor beta (ERbeta) in
      biphasic malignant pleural mesothelioma cells.
AB  - Biphasic malignant pleural mesothelioma (MPM) is the second most common histotype
      of MPM. It is histologically characterized by the concomitant presence of
      epithelioid and sarcomatoid features, the latter associated with worse prognosis.
      In this report we describe that silencing of AKT1 in spindle-shaped biphasic MPM
      cells promotes the shift toward an epithelioid phenotype. Furthermore, AKT1
      silencing resulted in decreased expression of the lactate/H+ symporter MCT4 and
      its chaperone CD147/Basigin, and in the induction of estrogen receptor beta
      (ERbeta) expression. We provide evidence that ERbeta expression is induced by
      increased intracellular lactate concentration. Spheroid culturing and tumor
      growth of ERbeta negative biphasic MPM in nude mice resulted in the induction of
      ERbeta expression and response to the selective agonist KB9520. In both models,
      the treatment with the ERbeta agonist results in reduced cell proliferation,
      decreased expression of MCT4 and CD147/Basigin and increased acetylation and
      inactivation of AKT1. Collectively, in response to metabolic changes, ERbeta
      expression is induced and exerts an anti-tumor effect through selective agonist
      activation. The possibility to reverse the more aggressive biphasic mesothelioma
      histotype by targeting ERbeta with a selective agonist could represent a new
      effective treatment strategy. 

PMID- 26208480
TI  - A meta-analysis including dose-response relationship between night shift work and
      the risk of colorectal cancer.
AB  - A meta-analysis was conducted to quantitatively evaluate the correlation between
      night shift work and the risk of colorectal cancer. We searched for publications
      up to March 2015 using PubMed, Web of Science, Cochrane Library, EMBASE and the
      Chinese National Knowledge Infrastructure databases, and the references of the
      retrieved articles and relevant reviews were also checked. OR and 95% CI were
      used to assess the degree of the correlation between night shift work and risk of
      colorectal cancer via fixed- or random-effect models. A dose-response meta
      analysis was performed as well. The pooled OR estimates of the included studies
      illustrated that night shift work was correlated with an increased risk of
      colorectal cancer (OR = 1.318, 95% CI 1.121-1.551). No evidence of publication
      bias was detected. In the dose-response analysis, the rate of colorectal cancer
      increased by 11% for every 5 years increased in night shift work (OR = 1.11, 95%
      CI 1.03-1.20). In conclusion, this meta-analysis indicated that night shift work
      was associated with an increased risk of colorectal cancer. Further researches
      should be conducted to confirm our findings and clarify the potential biological
      mechanisms. 

PMID- 26208481
TI  - MDA5 complements TLR3 in suppression of neuroblastoma.
AB  - Toll-like receptor3 (TLR3) has been confirmed to be differentially expressed in
      neuroblastoma (NB), and predicts a favorable prognosis with a high expression in
      tumor tissues. Treatment with TLR3 agonist--polyinosinic-polycytidylic acid
      [poly(I:C)] could induce significant but limited apoptosis in TLR3-expressing NB
      cells, suggesting that other viral RNA sensors, including melanoma
      differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG
      I) in the cytosolic compartment might also be implicated in poly(I:C)-induced NB
      cell death. MDA5 and RIG-I were induced by poly(I:C) to express in two of six NB
      cell lines, SK-N-AS (AS) and SK-N-FI, which were associated with up-regulation of
      caspase9 and active caspase3. While knockdown of either MDA5 or RIG-I alone is
      ineffective to decrease caspase9 and active caspase3, simultaneously targeting
      MDA5 and TLR3 showed the best effect to rescue poly(I:C) induced up-regulation of
      mitochondrial antiviral signaling protein (MAVS), caspase9, active caspase3, and
      apoptosis in AS cells. Over-expression of MDA5 in FaDu cells resulted in
      significantly less colony formation and more poly(I:C)-induced cell death.
      Further studies in human NB tissue samples revealed that MDA5 expression in NB
      tissues predicted a favorable prognosis synergistically with TLR3. Our findings
      indicate that MDA5 may serve as a complementary role in the TLR3 activated
      suppression of NB.

PMID- 26208483
TI  - Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.
AB  - In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov
      identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor
      RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption."
      The purpose of the current study was to assess in the full patient cohort the
      relationship between mid-treatment tumor RNA disruption and both pCR post
      treatment and, subsequently, disease-free survival (DFS) up to 108 months post
      treatment. To meet these objectives, we developed the RNA disruption assay (RDA)
      to quantify RNA disruption and stratify it into 3 response zones of clinical
      importance. Zone 1 is a level of RNA disruption inadequate for pathologic
      complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high
      RNA disruption. The same RNA disruption cut points developed for pCR response
      were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non
      responders than did clinical response by calipers. pCR responders were clustered
      in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for
      patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival
      curves corroborated these findings that high tumor RNA disruption was associated
      with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR
      were similar to that of pCR recipients across tumor subtypes, including patients
      with hormone receptor positive tumors that seldom achieve a pCR. RDA appears
      superior to pCR as a chemotherapy response biomarker, supporting the prospect of
      its use in response-guided chemotherapy.

PMID- 26208482
TI  - Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR,
      and MGMT-dependent DNA repair mechanisms.
AB  - Alkylating agents are frequently used as first-line chemotherapeutics for various
      newly diagnosed cancers. Disruption of genome integrity by such agents can lead
      to cell lethality if DNA lesions are not removed. Several DNA repair mechanisms
      participate in the recovery of mono- or bi-functional DNA alkylation. Thus, DNA
      repair capacity is correlated with the therapeutic response. Here, we assessed
      the function of novel water-soluble N-mustard BO-1055 (ureidomustin) in DNA
      damage response and repair mechanisms. As expected, BO-1055 induces ATM and ATR
      mediated DNA damage response cascades, including downstream Chk1/Chk2
      phosphorylation, S/G2 cell-cycle arrest, and cell death. Further investigation
      revealed that cell survival sensitivity to BO-1055 is comparable to that of
      mitomycin C. Both compounds require nucleotide excision repair and homologous
      recombination, but not non-homologous end-joining, to repair conventional cross
      linking DNA damage. Interestingly and unlike mitomycin C and melphalan, MGMT
      activity was also observed in BO-1055 damage repair systems, which reflects the
      occurrence of O-alkyl DNA lesions. Combined treatment with ATM/ATR kinase
      inhibitors significantly increases BO-1055 sensitivity. Our study pinpoints that
      BO-1055 can be used for treating tumors that with deficient NER, HR, and MGMT DNA
      repair genes, or for synergistic therapy in tumors that DNA damage response have
      been suppressed. 

PMID- 26208484
TI  - Poly (I: C) modulates the immunosuppressive activity of myeloid-derived
      suppressor cells in a murine model of breast cancer.
AB  - Polyinosinic-polycytidylic acid [Poly (I: C)], a ligand for Toll-like receptor
      (TLR-3), is used as an adjuvant to enhance anti-tumor immunity because of its
      prominent effects on CD8 T cells and NK cells. Myeloid-derived suppressor cells
      (MDSCs) are one of the main immunosuppressive factors in cancer, and their
      abnormal accumulation is correlated with the clinical stage of breast cancer and
      is an important mechanism of tumor immune evasion. Although Poly (I: C) is
      thought to have direct anti-tumor activity in different cell lines, its effect on
      immunosuppressive MDSCs in tumor-bearing animals has not been studied. 4T1-Luc, a
      metastatic breast cancer mouse cell line, was injected into the left flank of
      female BALB/c mice. Tumor-bearing mice were treated with i.p. injection of Poly
      (I: C) or PBS beginning on day 7 after tumor inoculation. WBCs and MDSCs were
      counted using coulter counter and stained for flow cytometry, respectively.
      Bioluminescent imaging was used to monitor tumor burden at multiple time points
      during the course of tumor growth. Poly (I: C) treatment led to a decrease in
      MDSC frequencies in BM, blood, and tumor compared to saline-treated control mice.
      Poly (I: C) treatment also abrogated the immunosuppressive function of MDSCs,
      concomitant with an increase in local T cell response of the immune system in a
      murine model of breast cancer. Poly (I: C) treatment decreases MDSC frequency and
      immunosuppressive function in 4T1-tumor-bearing hosts and effectively augments
      the activity of breast cancer immunotherapy. 

PMID- 26208485
TI  - Association of tamoxifen use and ovarian function in patients with invasive or
      pre-invasive breast cancer.
AB  - The impact of long-term tamoxifen therapy on ovarian function is not known.
      Understanding these effects will help reproductive-aged patients who desire
      future pregnancy make more informed decisions regarding their treatment. This is
      a retrospective cohort study in patients identified through the UCSF Cancer
      Registry and SPORE database. We enrolled women with a history of ductal carcinoma
      in situ (DCIS) or early stage invasive breast cancer who were premenopausal at
      diagnosis and did not receive chemotherapy. Menstrual histories were obtained
      through electronic and paper surveys. We compared the age of menopause onset and
      menstrual pattern changes between women who received tamoxifen (TAM) and those
      who did not receive tamoxifen (control). Neither group received chemotherapy. 250
      subjects were included in this study (125 TAM, 125 control). Mean age of
      menopause onset was 51.0 for both the groups and was not associated with duration
      of tamoxifen use or the age at tamoxifen initiation. Menstrual pattern changes,
      including amenorrhea, were more frequent in the TAM group than control group (any
      change: 48% TAM vs. 15 % control, p < 0.001; amenorrhea: 22% TAM vs. 3% control,
      p < 0.001). Older age was associated with an increased risk of developing
      amenorrhea within 6 months of starting tamoxifen (HR 1.32, p < 0.001). Menstrual
      pattern changes are common in premenopausal women taking tamoxifen. Tamoxifen use
      in the absence of chemotherapy is not associated with an earlier age onset of
      menopause in patients with DCIS or invasive breast cancer and is unlikely to
      significantly accelerate ovarian aging.

PMID- 26208486
TI  - Chronic oxidative stress causes estrogen-independent aggressive phenotype, and
      epigenetic inactivation of estrogen receptor alpha in MCF-7 breast cancer cells.
AB  - The role of chronic oxidative stress in the development and aggressive growth of
      estrogen receptor (ER)-positive breast cancer is well known; however, the
      mechanistic understanding is not clear. Estrogen-independent growth is one of the
      features of aggressive subtype of breast cancer. Therefore, the objective of this
      study was to evaluate the effect of oxidative stress on estrogen sensitivity and
      expression of nuclear estrogen receptors in ER-positive breast cancer cells. MCF
      7 cells chronically exposed to hydrogen peroxide were used as a cell model in
      this study, and their growth in response to 17-beta estradiol was evaluated by
      cell viability, cell cycle, and cell migration analysis. Results were further
      confirmed at molecular level by analysis of gene expressions at transcript and
      protein levels. Histone H3 modifications, expression of epigenetic regulatory
      genes, and the effect of DNA demethylation were also analyzed. Loss of growth in
      response to estrogen with a decrease in ERalpha expression was observed in MCF-7
      cells adapted to chronic oxidative stress. Increases in mtTFA and NRF1 in these
      cells further suggested the role of mitochondria-dependent redox-sensitive growth
      signaling as an alternative pathway to estrogen-dependent growth. Changes in
      expression of epigenetic regulatory genes, levels of histone H3 modifications as
      well as significant restorations of both ERalpha expression and estrogen response
      by 5-Aza-2'-deoxycytidine further confirmed the epigenetic basis for estrogen
      independent growth in these cells. In conclusion, results of this study suggest
      that chronic oxidative stress can convert estrogen-dependent nonaggressive breast
      cancer cells into estrogen-independent aggressive form potentially by epigenetic
      mechanism. 

PMID- 26208487
TI  - Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with
      activation of AKT and tamoxifen resistance in breast cancer.
AB  - Breast cancer is a heterogeneous disease and new clinical markers are needed to
      individualise disease management and therapy further. Alterations in the PI3K/AKT
      pathway, mainly PIK3CA mutations, have been shown frequently especially in the
      luminal breast cancer subtypes, suggesting a cross-talk between ER and PI3K/AKT.
      Aberrant PI3K/AKT signalling has been connected to poor response to anti
      oestrogen therapies. In vitro studies have shown protein tyrosine phosphatase,
      non-receptor type 2 (PTPN2) as a previously unknown negative regulator of the
      PI3K/AKT pathway. Here, we evaluate possible genomic alterations in the PTPN2
      gene and its potential as a new prognostic and treatment predictive marker for
      endocrine therapy benefit in breast cancer. PTPN2 gene copy number was assessed
      by real-time PCR in 215 tumour samples from a treatment randomised study
      consisting of postmenopausal patients diagnosed with stage II breast cancer 1976
      1990. Corresponding mRNA expression levels of PTPN2 were evaluated in 86
      available samples by the same methodology. Gene copy loss of PTPN2 was detected
      in 16% (34/215) of the tumours and this was significantly correlated with lower
      levels of PTPN2 mRNA. PTPN2 gene loss and lower mRNA levels were associated with
      activation of AKT and a poor prognosis. Furthermore, PTPN2 gene loss was a
      significant predictive marker of poor benefit from tamoxifen treatment. In
      conclusion, genomic loss of PTPN2 may be a previously unknown mechanism of
      PI3K/AKT upregulation in breast cancer. PTPN2 status is a potential new clinical
      marker of endocrine treatment benefit which could guide further individualised
      therapies in breast cancer.

PMID- 26208488
TI  - Localized experimental bone metastasis drives osteolysis and sensory
      hypersensitivity at distant non-tumor-bearing sites.
AB  - Patients with breast cancer metastasis to bone suffer from inadequate pain
      relief. Animal models provide increased understanding of cancer-induced bone and
      sensory alterations. The objective of this study was to investigate the measures
      of pain at distant non-tumor-bearing sites in animals with localized bone
      metastasis. Immunocompetent BALB/c mice are injected intra-tibially with murine
      mammary carcinoma cells (4T1) or saline, and the sensitivity to mechanical and
      thermal stimuli in the contralateral paw was examined. In addition to previously
      demonstrated development of osteolysis and hypersensitivity to mechanical and
      thermal stimuli in the cancer-injected tibia, these animals exhibited an increase
      in sensory hypersensitivity in the contralateral limb. No bone lesions were
      evident on radiographs of the contralateral limbs. Histomorphometry detected
      decreased bone volume per tissue volume and increased osteoclast number in the
      contralateral tibia and vertebral bones of cancer-bearing animals.
      Neuroplasticity was examined by immunofluorescence for calcitonin gene-related
      peptide (CGRP) in sensory neurons and glial fibrillary acidic protein (GFAP) in
      lumbar spinal cords. CGRP-immunoreactivity and GFAP-immunoreactivity were
      significantly elevated both ipsilateral and contralateral in tumor-bearing
      animals. The anti-inflammatory and osteolysis-targeting drug rapamycin reduced
      hypersensitivity to mechanical and cold stimuli, attenuated GFAP over-expression,
      and lowered osteoclast number. The osteoclast-targeting drug pamidronate reduced
      sensitivity to cold and protected against bone loss. Localized bone cancer drives
      hypersensitivity, bone remodeling, and sensory neuron plasticity at sites distant
      from the primary tumor area. Drugs targeting these mechanisms may be useful in
      the treatment of pain distant from the primary tumor site. 

PMID- 26208489
TI  - Treatment of Mild Cognitive Impairment.
AB  - OPINION STATEMENT: It is increasingly evident that early identification of
      cognitive impairment in older adults presents opportunities for interventions
      that aim to mitigate the impact of cognitive symptoms on daily function and that
      attempt to delay (or ultimately prevent) progression from mild cognitive
      impairment (MCI) to dementia. To date, no intervention has proven protective in
      ultimately preventing conversion to dementia. However, several lifestyle,
      dietary, and pharmacologic interventions have suggested symptomatic benefit for
      those having MCI. A number of diet and lifestyle recommendations have been
      associated with decreased risk of dementia both in cognitively intact older
      adults and in those having mild cognitive impairment. Thus, these recommendations
      may be appropriate for both people presenting with subjective cognitive concerns
      and for those having objective evidence of memory problems. It remains less
      certain whether adopting these lifestyle habits in later life confers the
      benefits seen in epidemiological cohorts (where people have likely practiced them
      for many years). Discussion of starting on a cholinesterase inhibitor is
      appropriate for those having MCI, particularly those in whom the MCI is thought
      to have a vascular etiology or to represent the prodromal stage of a
      neurodegenerative disease. Recent meta-analyses exploring the use of
      cholinesterase inhibitors in patients having MCI have concluded that there is no
      evidence to support this practice. Although meta-analytic techniques seemingly
      strengthen the confidence in a recommendation via the incorporation of a large
      number of subjects analyzed, the technique is not capable of overcoming any
      inherent weaknesses of the individual studies included in the analysis. It is
      arguable whether studies in MCI may have employed endpoints poorly adapted to
      investigating effect of cholinesterase inhibitors. Most studies have used
      cognitive screening examinations, all of which stretch their detection ability to
      identify subjects with MCI, let alone discriminate subtle differences between
      them. Some have used conversion from MCI to dementia as an endpoint, which may
      not be the best measure for a symptomatic treatment. Further, once conversion to
      dementia has occurred, a cholinesterase inhibitor would be started in most (if
      not all) clinical settings, a reality not well reflected in most study designs.
      Additionally, several large studies have not permitted subject stratification by
      APOE carrier status, another important defect in assessing outcome. In clinical
      practice, our center typically does recommend cholinesterase inhibitors for
      patients having MCI. Despite the modest effect size, many patients do wish to
      start on treatment. It appears that this is a generally accepted practice and
      experience, as most clinical trials for prodromal Alzheimer's disease specify
      that participants should be taking a cholinesterase inhibitor.

PMID- 26208490
TI  - Rare diploid females coexist with rare males: a novel finding in triploid
      parthenogenetic populations in the psyllid Cacopsylla myrtilli (W. Wagner, 1947)
      (Hemiptera, Psylloidea) in northern Europe.
AB  - Using a cytological approach, diploid females were found coexisting with rare
      males in triploid apomictic parthenogenetic populations of the psyllid Cacopsylla
      myrtilli (W. Wagner, 1947) in Norway, Sweden, Finland and northwest Russia.
      Diploid females were easily distinguished from triploid apomictic females by the
      presence of 13 chiasmate bivalents instead of 39 univalent chromosomes at
      metaphase I. Abundance equaled that of males, but the proportion of males and
      diploid females was significantly greater in high altitude compared with low
      altitude populations. Males mated with females but showed no mating preference
      for diploid females. Lack of genuine bisexual reproduction owing to either
      asynaptic meiosis in males, or rarity of males with normal meiosis, suggests that
      diploids are produced in every generation by parthenogenetic females as reversals
      from triploidy, with their production being enhanced by environmental factor(s)
      associated with high altitude. This is further supported by the observation that
      within a population the COI haplotype found in rare males was the same as that in
      parthenogenetic triploid females. Thus, in northern Europe parthenogenesis in C.
      myrtilli is obligate, geographic parthenogenesis. Bisexual populations of C.
      myrtilli should be looked for in Central and Southern Europe. From the
      evolutionary point of view, the presence of males and diploid females with normal
      meiosis in parthenogenetic populations could be significant as they exhibit the
      potential to re-evolve either a new sexual species of parthenogenetic ancestry or
      a new parthenogenetic species by contagious parthenogenesis.

PMID- 26208491
TI  - Degradation of ciprofloxacin in water by advanced oxidation process: kinetics
      study, influencing parameters and degradation pathways.
AB  - Gamma-radiation-induced degradation of ciprofloxacin (CIP) in aqueous solution
      and the factors affecting the degradation process have been investigated. The
      results showed that CIP (4.6 mg/L) was almost completely degraded at an absorbed
      dose of 870 Gy. The kinetic studies of aqueous solutions containing 4.6, 10, 15
      and 17.9 mg/L indicated that the decomposition of CIP by gamma irradiation
      followed pseudo-first-order kinetics and the decay constant (k) decreased from
      5.9  *  10(-3) to 1.6  *  10(-3) Gy(-1) with an increase in CIP initial
      concentration from 4.6 to 17.9 mg/L. The effect of saturation of CIP solution
      with N2, N2O or air on radiation-induced degradation of CIP was also
      investigated. The effects of radical scavengers, such as t-BuOH and i-PrOH,
      showed the role of reactive radicals towards degradation of CIP in the order of
      OH > e(aq)- . H. The apparent second-order rate constant of [Formula: see text]
      with CIP was calculated to be 2.64 * 10(9) M(-1) s(-1). The effects of solution
      pH as well as natural water contaminants, such as [HCO3-, CO3(2-), and NO2-, on
      CIP degradation by gamma-irradiation were also investigated. Major degradation
      products, including organic acids, were identified using UPLC-MS/MS and IC, and
      degradation pathways have been proposed.

PMID- 26208492
TI  - Is there association between Glutathione S Transferases polymorphisms and
      cataract risk: a meta-analysis?
AB  - BACKGROUND: Glutathione S transferase (GST) polymorphisms have been considered as
      risk factors for age-related cataracts, but the results remain controversial. In
      this study, we have performed a meta-analysis to evaluate the association between
      polymorphisms of GSTM1 and GSTT1 and cataract risk. METHODS: Published literature
      from PubMed and other databases were retrieved. The case-control studies
      regarding the association between GSTM1 or GSTT1 polymorphism and cataract risk
      were included. Pooled odds ratio (OR) and 95 % confidence interval (CI) were
      calculated using random- or fixed-effects model. RESULTS: Fifteen studies on
      GSTM1 (3,065 patients and 2,105 controls), and nine studies on GSTT1 (2,374
      patients and 1,544 controls) were included. By pooling all the studies, GSTM1
      null polymorphism was not associated with cataract risk, and this negative
      association maintained in subgroup analyses. However, GSTT1 null polymorphism was
      significantly associated with increased risk of posterior subcapsular (OR, 1.42;
      95 % CI, 1.04-1.94) but not other subtypes of cataract. Stratified analyses
      demonstrated an association of GSTT1 null genotype with increased risk of
      cataract in Asian (OR, 1.44; 95 % CI, 1.14-1.83) but not Caucasian populations.
      In addition, seven pooled studies showed no association of cataract risk with the
      combined GSTM1 and GSTT1 null genotypes. CONCLUSIONS: This meta-analysis suggests
      that GSTT1 null polymorphism is associated with increased risk of posterior
      subcapsular cataract. Given the limited sample size, the association between
      GSTT1 null polymorphism and cataract risk in Asian awaits further investigation.

PMID- 26208493
TI  - Excellent long-term outcome of renal transplantation in cystinosis patients.
AB  - BACKGROUND: Cystinosis is a rare lysosomal disorder leading to end stage renal
      disease in more than 90 % of patients before 20 years of age. Data about safety
      and efficiency of renal transplantation in patients with cystinosis is scarce. We
      evaluated long-term outcomes of renal transplantation in adult patients with
      cystinosis. METHODS: Data of renal transplantation (n = 31) in 30 adult patients
      with cystinosis in 5 French university transplant centers between 1980 and 2013
      were retrospectively analyzed. A control cohort of 93 patients was matched for
      age, graft date, living/deceased donor status and transplant center. RESULTS:
      Median age at transplantation was 20.4 years (7-36.5). At transplantation, all
      patients with cystinosis had corneal cystine deposits, 3 had diabetes and 7 had
      hypothyroidism. Graft survival was better in patients with cystinosis than in
      control patients (p = 0.013). Multivariate analysis confirmed that cystinosis was
      an independent protective factor for graft survival (Hazard Ratio (HR) 0.11; CI95
      [0.02-0.61]). Specific complications of cystinosis occurred during follow up:
      diabetes mellitus (n = 4), hypothyroidism (n = 1), liver involvement (n = 1),
      neurologic involvement (n = 2). Proportion of post-transplant diabetes mellitus
      (PTDM) was not statistically different in cystinosis group compared to control
      group: 4 (13.0 %) compared to 5 (5.0 %), respectively (p = 0.25), with no
      differences regarding calcineurin inhibitors and steroids treatments during
      follow-up. CONCLUSIONS: Renal transplantation appears to be safe with excellent
      long-term outcomes in patients with cystinosis. These patients may receive
      standard immunosuppressive regimens with steroids and calcineurin inhibitors.

PMID- 26208494
TI  - Risk factors for febrile respiratory illness and mono-viral infections in a semi
      closed military environment: a case-control study.
AB  - BACKGROUND: Febrile respiratory illness (FRI) results in substantial burden in
      semi-closed environments. Tackling risk factors may reduce transmission and
      infection. However, risk factors involved in one setting may not be generalizable
      in all settings due to differences in climate, residential environment,
      population genetic and cultural backgrounds. This study aims to identify risk
      factors of FRI and mono-viral infections in a tropical military environment.
      METHODS: From year 2009 to 2012, military personnel with temperature >=37.5 
      degrees C, cough and/or sore throat, and personnel with no fever or no
      respiratory symptoms were recruited as cases and controls, respectively. Subjects
      provided nasal wash specimens and answered a standardized questionnaire. Resplex
      assays were used to determine the viral etiologies. Descriptive, univariate and
      multivariate analyses of the variables were performed using appropriate
      descriptive tests and logistic regression modelling, respectively, with R
      program. RESULTS: A total of 7,743 FRI cases and 1,247 non-FRI study controls
      were recruited. Increasing age [adjusted odds ratio (AOR) = 1.03; 95 % confidence
      interval (CI) = 1.01-1.05], recruit camp (AOR = 4.67; 95 % CI = 3.99-5.46) and
      smoker (AOR = 1.31; 95 % CI = 1.13-1.52) were independent risk factors of FRI.
      Malay ethnicity was positively associated with influenza A(H1N1)pdm09 (AOR =
      1.50; 95 % CI = 1.04-2.15) and coxsackie/echovirus (AOR = 1.67; 95 % CI = 1.19
      2.36) mono-infection. Significant contact risk factors were stay-out personnel
      with ill household member (AOR = 4.96; 95 % CI = 3.39-7.24), and stay-in
      personnel with ill bunkmate and household member (AOR = 3.55; 95 % CI = 2.57
      4.91). Staying in camp with none ill in bunk and at home was a protective factor
      against FRI (AOR = 0.80; 95 % CI = 0.64-0.99). These contact risk factors were
      similarly observed for the five most common viruses detected, namely adenovirus,
      rhinoviruses, influenza A and B, and coxsackie/echovirus. CONCLUSION: Increasing
      age, smoker, recruit-camp, stay-out personnel with ill household members and stay
      in personnel with ill bunkmates were independent risk factors of FRI in a semi
      closed military environment. Early identification and isolation of ill personnel
      from their bunk may be effective to prevent and reduce transmission and disease
      burden.

PMID- 26208495
TI  - Comparing caries risk profiles between 5- and 10- year-old children with cleft
      lip and/or palate and non-cleft controls.
AB  - BACKGROUND: Previous studies have suggested that children with oral clefts may
      have higher caries prevalence in comparison with non-cleft controls but the
      relative importance of the potential risk factors is not clear. The aim of this
      study was to compare the caries risk profiles in a group of cleft lip and/or
      palate (CL(P)) children with non-cleft controls in the same age using a
      computerized caries risk assessment model. METHODS: The study group consisted of
      133 children with CL(P) (77 subjects aged 5 years and 56 aged 10 years) and 297
      non-cleft controls (133 aged 5 years and 164 aged 10 years). A questionnaire was
      used to collect data concerning the child's oral hygiene routines, dietary habits
      and fluoride exposure. Oral hygiene was assessed using Quigley-Hein plaque Index
      and the caries prevalence and frequency was scored according to the International
      Caries Detection and Assessment System. Whole saliva samples were analyzed for
      mutans streptococci, lactobacilli, buffering capacity and secretion rate. The
      risk factors and risk profiles were compared between the groups with aid of
      Cariogram and the estimated risk for future caries was categorized as "high" or
      "low". RESULTS: Children with CL(P) (the entire study group) had significantly
      higher counts of salivary lactobacilli (p < 0.05) and displayed less good oral
      hygiene (p < 0.05). More 10-year-old children in the CL(P) group had low
      secretion rate but this difference was not significant. The average chance to
      avoid caries ranged from 59 to 67% but there were no significant differences
      between the groups. The odds of being categorized with high caries risk in the
      CL(P) group was significantly elevated (OR = 1.89; 95% CI = 1.25-2.86). In both
      groups, children in the high risk category had a higher caries experience than
      those with low risk. CONCLUSION: Children with CL(P) displayed increased odds of
      being categorized at high caries risk with impaired oral hygiene and elevated
      salivary lactobacilli counts as most influential factors. The results suggest
      that a caries risk assessment model should be applied in the routine CL(P) care
      as a basis for the clinical decision-making and implementation of primary and
      secondary caries prevention.

PMID- 26208496
TI  - Massive interstitial copy-neutral loss-of-heterozygosity as evidence for cancer
      being a disease of the DNA-damage response.
AB  - BACKGROUND: The presence of loss-of-heterozygosity (LOH) mutations in cancer cell
      genomes is commonly encountered. Moreover, the occurrences of LOHs in tumor
      suppressor genes play important roles in oncogenesis. However, because the
      causative mechanisms underlying LOH mutations in cancer cells yet remain to be
      elucidated, enquiry into the nature of these mechanisms based on a comprehensive
      examination of the characteristics of LOHs in multiple types of cancers has
      become a necessity. METHODS: We performed next-generation sequencing on inter-Alu
      sequences of five different types of solid tumors and acute myeloid leukemias,
      employing the AluScan platform which entailed amplification of such sequences
      using multiple PCR primers based on the consensus sequences of Alu elements; as
      well as the whole genome sequences of a lung-to-liver metastatic cancer and a
      primary liver cancer. Paired-end sequencing reads were aligned to the reference
      human genome to identify major and minor alleles so that the partition of LOH
      products between homozygous-major vs. homozygous-minor alleles could be
      determined at single-base resolution. Strict filtering conditions were employed
      to avoid false positives. Measurements of LOH occurrences in copy number
      variation (CNV)-neutral regions were obtained through removal of CNV-associated
      LOHs. RESULTS: We found: (a) average occurrence of copy-neutral LOHs amounting to
      6.9% of heterologous loci in the various cancers; (b) the mainly interstitial
      nature of the LOHs; and (c) preference for formation of homozygous-major over
      homozygous-minor, and transitional over transversional, LOHs. CONCLUSIONS: The
      characteristics of the cancer LOHs, observed in both AluScan and whole genome
      sequencings, point to the formation of LOHs through repair of double-strand
      breaks by interhomolog recombination, or gene conversion, as the consequence of a
      defective DNA-damage response, leading to a unified mechanism for generating the
      mutations required for oncogenesis as well as the progression of cancer cells.

PMID- 26208497
TI  - Robotic versus laparoscopic gastrectomy for gastric cancer: comparison of short
      term surgical outcomes.
AB  - BACKGROUND: Robot-assisted gastrectomy (RAG) is a new minimally invasive surgical
      technique for gastric cancer. This study was designed to compare RAG with
      laparoscopy-assisted gastrectomy (LAG) in short-term surgical outcomes. METHODS:
      Between October 2011 and August 2014, 423 patients underwent robotic or
      laparoscopic gastrectomy for gastric cancer: 93 RAG and 330 LAG. We performed a
      comparative analysis between RAG group and LAG group for clinicopathological
      characteristics and short-term surgical outcomes. RESULTS: RAG was associated
      with a longer operative time (P < 0.001), lower blood loss (P = 0.001), and more
      harvested lymph nodes (P = 0.047). Only three patients in LAG group had positive
      margins, and R0 resection rate for RAG and LAG was similar (P = 0.823). The RAG
      group had postoperative complications of 9.8 %, comparable with those of the LAG
      group (P = 0.927). Proximal margin, distal margin, hospital stay, days of first
      flatus, and days of eating liquid diet for RAG and LAG were similar. In the
      subgroup of serosa-negative patients, RAG had a longer operation time (P =
      0.003), less intraoperative blood loss (P = 0.005), and more harvested lymph
      nodes (P = 0.04). However, in the subgroup of serosa-positive patients, RAG had a
      longer operation time (P = 0.001), but no less intraoperative blood loss (P =
      0.139) and no more harvested lymph nodes (P = 0.139). Similarly, in the subgroup
      of total gastrectomy patients, RAG had a longer operation time (P = 0.018), but
      no less intraoperative blood loss (P = 0.173). CONCLUSIONS: The comparative study
      demonstrates that RAG is as acceptable as LAG in terms of surgical and oncologic
      outcomes. With lower estimated blood loss, acceptable complications, and radical
      resection, RAG is a promising approach for the treatment of gastric cancer.
      However, the indication of patients for RAG is critical.

PMID- 26208498
TI  - Multicenter prospective evaluation of a new articulating 5-mm endoscopic linear
      stapler.
AB  - BACKGROUND: The objective of this study was to evaluate the safety and efficacy
      of a novel 5-mm laparoscopic linear stapler in clinical gastrointestinal surgical
      applications. METHODS: A prospective, single-arm study with an open enrollment of
      subjects requiring stapling of the gastrointestinal (GI) tract was performed. The
      study endpoints were the number of complications and technical failures
      associated with the use of a novel stapler when compared to similar events with
      conventional staplers as described in the medical literature. RESULTS: Seven
      centers enrolled 160 subjects, 150 of which were followed up to at least 30 days
      postoperatively. Intraoperative success: In 423 deployments, there were two
      staple line leaks and five staple line bleeds, all of which were intraoperatively
      resolved. In addition, incomplete staple lines were noted as a result of user
      error (n = 15) or device-related issues (n = 22), all of which were immediately
      resolved and none of which resulted in a complication or a change of the surgical
      procedure. Late outcomes: A total of 13 surgical complications in 160 patients
      were related to a GI transection or anastomosis, 12 of which related to a hand
      sewn anastomosis or use of other commercially available staplers. One event
      (1/153, 0.065 %) on POD 1, involving bleeding of the staple line, was felt to be
      related to the use of the new stapler. CONCLUSION: The study confirmed that the
      new device was user-friendly (9 % incidence of problems firing the device),
      reliable (3 % device failures) and safe (<1 % complication rate related to the
      stapler). Based on these results, it would seem that this new 5-mm stapler is a
      safe and effective alternative to standard 12-mm staplers.

PMID- 26208499
TI  - Evaluation of laparoscopic total gastrectomy for advanced gastric cancer: results
      of a comparison with laparoscopic distal gastrectomy.
AB  - OBJECTIVE: To validate the efficacy and safety of laparoscopic total gastrectomy
      (LTG) for advanced gastric cancer (AGC). BACKGROUND: Laparoscopic distal
      gastrectomy (LDG) in the treatment of patients with local AGC is becoming
      increasingly popular, and there have been several multicenter randomized
      controlled trials focused on this treatment. However, few reports on the
      procedure of LTG for AGC exist. METHODS: The data of 976 patients who underwent
      LTG for AGC were retrieved from a prospectively constructed database of 2170
      patients who underwent laparoscopic gastrectomy between 2007 and 2013. Surgical
      outcomes of LTG were investigated and compared with those of patients who
      underwent LDG. RESULTS: LTG was associated with significantly longer operation
      time, number of dissected lymph nodes, and time of resume soft diet compared with
      the LDG group. According to Clavien-Dindo classification, the morbidity and
      mortality rates of the LTG group were comparable to those of the LDG group.
      Multivariate analyses revealed that elderly patients, more comorbidities, and
      longer operation time were the significant independent risk factors for
      determining postoperative complications. The difference in overall survival rates
      between the two groups was statistically significant. However, a comparative
      analysis of overall survival showed no statistical significance for any of the
      stages of cancer between the LTG and LDG groups. CONCLUSIONS: The study findings
      suggest that LTG is an oncologically safe procedure for AGC yields comparable
      surgical outcomes. A well-designed phase III trial can be carried out to provide
      valuable evidence for the oncologic safety of LTG for the treatment of AGC.

PMID- 26208500
TI  - Communities of practice for supporting health systems change: a missed
      opportunity.
AB  - BACKGROUND: Communities of practice (CoPs) have been used in the health sector to
      support professional practice change. However, little is known about how CoPs
      might be used to influence a system that requires change at and across various
      levels (i.e. front line care, organizational, governmental). In this paper we
      examine the experience of a CoP in the Canadian province of Ontario as it engages
      in improving the care of seniors. Our aim is to shed light on using CoPs to
      facilitate systems change. METHODS: This paper draws on year one findings of a
      larger multiple case study that is aiming to increase understanding of knowledge
      translation processes mobilized through CoPs. In this paper we strategically
      report on one case to illustrate a critical example of a CoP trying to effect
      systems change. Primary data included semi-structured interviews with CoP members
      (n = 8), field notes from five planning meetings, and relevant background
      documents. Data analysis included deductive coding (i.e. pre-determined codes
      aligned with the larger project) and inductive coding which allowed codes and
      themes to emerge. A thorough description of the case was prepared using all the
      coded data. RESULTS: The CoP recognized a need to support health professionals
      (nurses, dentists) and related paraprofessionals with knowledge, experience, and
      resources to appropriately address their clients' oral health care needs.
      Accordingly, the CoP led a knowledge-to-action initiative that involved a seven
      part webinar series meant to transfer step-by-step, skill-based knowledge through
      live and archived webinars. Although the core planning team functioned
      effectively to develop the webinars, the CoP was challenged by organizational and
      long-term care sector cultures, as well as governmental structures within the
      broader health context. CONCLUSION: The provincial CoP functioned as an incubator
      that brought together best practices, research, experiences, a reflective
      learning cycle, and passionate champions. Nevertheless, the CoP's efforts to
      stimulate practice changes were met with broader resistance. Research about how
      to use CoPs to influence health systems change is needed given that CoPs are
      being tasked with this goal.

PMID- 26208501
TI  - Folate deficiency in an unselected population in Calgary, Alberta and its
      relationship with red blood cell macrocytosis.
AB  - BACKGROUND: Folate deficiency is rare in western countries and therefore blood
      tests for folate level have limited indications. One such indication is red cell
      macrocytosis, however it is unclear if the association of macrocytosis with
      folate deficiency is robust enough to serve as a risk marker. Our objective is to
      determine whether macrocytosis is a useful marker for folate deficiency.
      FINDINGS: Paired data from the Calgary Laboratory Services Information System was
      analyzed using receiver operating characteristic (ROC) curves to determine
      strength of association between mean corpuscular volume and serum folate.
      Strength of association was analyzed for serum folate cut-off values of 12, 10,
      8, and 6 nmol/L. Overall, 0.2% of individuals were folate deficient (<6 nmol/L
      serum folate). Based on ROC curves, at each cut-off level, mean corpuscular
      volume was a poor predictive marker for serum folate level. CONCLUSIONS: Folate
      deficiency is rare in Calgary, Alberta. Macrocytosis is not a strong predictor
      for folate deficiency.

PMID- 26208503
TI  - Fracturing the Ring of Small Mitroflow Bioprostheses by High-Pressure Balloon
      Predilatation in Transcatheter Aortic Valve-in-Valve Implantation.

PMID- 26208502
TI  - ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry.
AB  - Intermediate-length CAG expansions (encoding 27-33 glutamines, polyQ) of the
      Ataxin2 (ATXN2) gene represent a risk factor for amyotrophic lateral sclerosis
      (ALS). Recently, it has been proposed that >=31 CAG expansions may influence ALS
      phenotype. We assessed whether ATXN2 intermediate-length polyQ expansions
      influence ALS phenotype in a series of 375 patients of Sardinian ancestry.
      Controls were 247 neurologically healthy subjects, resident in the study area,
      age- and gender-matched to cases. The frequency of >=31 polyQ ATNX2 repeats was
      significantly more common in ALS cases (4 patients vs. no control, p = 0.0001).
      All patients with >=31 polyQ repeats had a spinal onset versus 73.3% of patients
      with <31 polyQ repeats. Patients with an increased number of polyQ repeats have a
      shorter survival than those with <31 repeats (1.2 vs. 4.2 years, p = 0.035). In
      this large series of ALS patients of Sardinian ancestry, we have found that >=31
      polyQ repeats of the ATXN2 gene influenced patients' phenotype, being associated
      to a spinal onset and a significantly shorter survival.

PMID- 26208504
TI  - Integrated systems approach identifies risk regulatory pathways and key
      regulators in coronary artery disease.
AB  - Coronary artery disease (CAD) is the most common type of heart disease. However,
      the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to
      play crucial roles in many pathogenic processes. Thus, inferring risk regulatory
      pathways is an important step toward elucidating the mechanisms underlying CAD.
      With advances in high-throughput data, we developed an integrated systems
      approach to identify CAD risk regulatory pathways and key regulators. Firstly, a
      CAD-related core subnetwork was identified from a curated transcription factor
      (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm.
      Secondly, candidate risk regulatory pathways were extracted from the subnetwork
      by applying a breadth-first search (BFS) algorithm. Then, risk regulatory
      pathways were prioritized based on multiple CAD-associated data sources. Finally,
      we also proposed a new measure to prioritize upstream regulators. We inferred
      that phosphatase and tensin homolog (PTEN) may be a key regulator in the
      dysregulation of risk regulatory pathways. This study takes a closer step than
      the identification of disease subnetworks or modules. From the risk regulatory
      pathways, we could understand the flow of regulatory information in the
      initiation and progression of the disease. Our approach helps to uncover its
      potential etiology. KEY MESSAGES: We developed an integrated systems approach to
      identify risk regulatory pathways. We proposed a new measure to prioritize the
      key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk
      regulatory pathways.

PMID- 26208505
TI  - Does the antenatal care visit represent a missed opportunity for increasing
      contraceptive use in Pakistan? An analysis of household survey data from Sindh
      province.
AB  - During the last two decades, the use of maternal health services has increased
      dramatically in Pakistan, with nearly 80% of Pakistani women making an antenatal
      care (ANC) visit during their pregnancy. Yet, this increase in use of modern
      health services has not translated into significant increases in the adoption of
      contraception. Even though Pakistan has had a national family planning programme
      and policies since the 1950s, contraceptive use has increased slowly to reach
      only 35% in 2012-13. No evidence is currently available to demonstrate whether
      the utilization of maternal health services is associated with contraceptive
      adoption in Pakistan. This study uses data from a large-scale survey conducted in
      Sindh province in 2013 to examine whether ANC utilization is a significant
      predictor of subsequent contraceptive use among women. In an analysis which
      controls for a range of variables known to be important for family planning
      adoption, the findings show that ANC is the strongest predictor of subsequent
      family planning use among women in Sindh. The antenatal visit represents an
      enormous opportunity to promote the adoption of family planning in Pakistan. The
      family planning programme should ensure that high-quality family planning
      counselling is provided to women during their ANC visits. This approach has the
      potential for contributing to substantial increases in contraceptive use in
      Pakistan. 

PMID- 26208506
TI  - Measuring costs of data collection at village clinics by village doctors for a
      syndromic surveillance system-a cross sectional survey from China.
AB  - BACKGROUND: Studies into the costs of syndromic surveillance systems are rare,
      especially for estimating the direct costs involved in implementing and
      maintaining these systems. An Integrated Surveillance System in rural China (ISSC
      project), with the aim of providing an early warning system for outbreaks, was
      implemented; village clinics were the main surveillance units. Village doctors
      expressed their willingness to join in the surveillance if a proper subsidy was
      provided. This study aims to measure the costs of data collection by village
      clinics to provide a reference regarding the subsidy level required for village
      clinics to participate in data collection. METHODS: We conducted a cross
      sectional survey with a village clinic questionnaire and a staff questionnaire
      using a purposive sampling strategy. We tracked reported events using the ISSC
      internal database. Cost data included staff time, and the annual depreciation and
      opportunity costs of computers. We measured the village doctors' time costs for
      data collection by multiplying the number of full time employment equivalents
      devoted to the surveillance by the village doctors' annual salaries and benefits,
      which equaled their net incomes. We estimated the depreciation and opportunity
      costs of computers by calculating the equivalent annual computer cost and then
      allocating this to the surveillance based on the percentage usage. RESULTS: The
      estimated total annual cost of collecting data was 1,423 Chinese Renminbi (RMB)
      in 2012 (P25 = 857, P75 = 3284), including 1,250 RMB (P25 = 656, P75 = 3000)
      staff time costs and 134 RMB (P25 = 101, P75 = 335) depreciation and opportunity
      costs of computers. CONCLUSIONS: The total costs of collecting data from the
      village clinics for the syndromic surveillance system was calculated to be low
      compared with the individual net income in County A.

PMID- 26208507
TI  - Cardiac rehabilitation in low- and middle-income countries: a review on cost and
      cost-effectiveness.
AB  - BACKGROUND: By 2030, more than 80% of cardiovascular disease-related deaths and
      disability-adjusted life years will occur in the 139 low- and middle-income
      (LMIC) countries. Cardiac rehabilitation (CR) has been demonstrated to be
      effective and cost-effective mainly based on data from high-income countries. The
      purpose of this paper was to review the literature for cost and cost
      effectiveness data on CR in LMICs. METHODS: MEDLINE (Ovid) and EMBASE (Ovid)
      electronic databases were searched for CR 'cost' and 'cost-effectiveness' data in
      LMICs. RESULTS: Five CR publications with cost and cost-effectiveness data from
      middle-income countries were identified with none from low-income countries.
      Studies from Brazil demonstrated mean monthly savings of US$190 for CR, with a
      US$48 increase in a control group with mean costs of US$503 for a 3-month CR
      program. Mean costs to the public health care system of US$360 and US$540 when
      paid out-of-pocket were reported for a 3-month CR program in seven Latin American
      middle-income countries. Cardiac rehabilitation is reported to be cost-effective
      in both Brazil and Colombia. CONCLUSIONS: Cardiac rehabilitation for patients
      with heart failure in Brazil and Colombia was estimated to be cost-effective.
      However, given the limited health care budgets in many LMICs, affordable CR
      models will need to be developed for LMICs, particularly for low-income
      countries.

PMID- 26208508
TI  - Neuroendocrine Carcinoma of Gall Bladder: A Series of 19 Cases with Review of
      Literature.
AB  - BACKGROUND: Neuroendocrine neoplasms of the gall bladder (GB) are rare tumors
      classified as grade 1 and 2 neuroendocrine tumor (NET), neuroendocrine carcinoma
      (large cell or small cell type), and mixed adeno-neuroendocrine carcinoma
      (MANEC). Primary neuroendocrine carcinomas (NEC) of GB are rare with grave
      prognosis not withstanding radical surgical treatment. Chemotherapy forms the
      primary management due to the advanced stage at presentation, as complete
      surgical resection is generally not possible. The overall median survival is 4-6
      months despite aggressive management. Only 73 cases of small cell carcinoma (SCC)
      and 10 cases of large cell neuroendocrine carcinoma (LCNEC) have been reported in
      English literature till now. We present a series of 19 cases of NEC of GB with
      their pathological and clinical features and response to treatment. OBJECTIVE:
      The objective of this study was to evaluate NECs of the GB for their clinical
      behavior, prognosis, and treatment outcome in terms of survival and to segregate
      NECs into further subcategories, that is 20-50 % and >50 %, based on MIB-1 index.
      METHODS: We retrospectively searched the clinical and pathological database over
      2.5 years (January 2012 to June 2014) through existing electronic hospital
      medical records to collect cases of NEC arising in GB. A total of 447 cases of
      gall bladder pathologies were analyzed, of which 19 cases were diagnosed as NEC.
      All relevant investigations were documented and response to treatment/therapy was
      evaluated clinically and radiologically. Tumor specimen was obtained by fine
      needle aspiration cytology and/or biopsy and classified using the latest World
      Health Organisation (WHO) classification (2010) via cytopathologic,
      histopathologic, and immunohistochemical visage. RESULTS: Nineteen patients
      diagnosed as NEC of GB were evaluated in the study, with 16 having SCC, 2 having
      LCNEC, and 1 with MANEC. All patients presented in advanced clinical stage III or
      IV, along with distant metastasis and showed progressive disease during therapy.
      Ki67 index was between 20 and 50 % in 5 cases and >50 % in 8 cases. Follow-up was
      available in 14 cases with a median survival of 3 months, and 2 of these patients
      capitulated to their illness, before commencement of treatment. The remaining 5
      cases were lost to follow-up. Out of these, 2 had deranged liver function test
      and no chemotherapy could be administered, and the other 3 refused treatment.
      CONCLUSIONS: NECs are aggressive with generally poor prognosis, characterized by
      insidious onset and advanced clinical stage of presentation. A radical approach
      to treatment with chemotherapy is the best form of palliation. Role of
      radiotherapy remains undefined due to paucity of data.

PMID- 26208509
TI  - Effect of Lateral Soft Tissue Release on Sesamoid Position in Hallux Valgus
      Surgery.
AB  - BACKGROUND: The effect of lateral soft tissue release (LSTR) regarding the
      position of the sesamoid is not clear. The purpose of this study was to evaluate
      the effect of LSTR by comparing the radiologic and clinical outcomes of operative
      treatment for hallux valgus with or without LSTR. METHODS: This study included a
      consecutive series of chevron osteotomy of 119 feet of 90 patients with
      symptomatic hallux valgus with incongruent first metatarsophalangeal (MTP)
      joints. Fifty-one feet underwent an operation with the LSTR procedure (LSTR
      group), and the remaining 68 feet underwent treatment without LSTR (control non
      LSTR group). We evaluated the differences regarding the distance of the fibular
      sesamoid from the second metatarsal bone between these 2 groups to evaluate the
      effect of LSTR on sesamoid position. The tibial sesamoid position was also
      investigated to evaluate the degree of reduction of the metatarsal head to the
      sesamoids. The hallux valgus angle, intermetatarsal angle, and distal metatarsal
      articulation angle were analyzed as radiologic outcomes. Additionally, the
      preoperative and final follow-up American Orthopaedic Foot & Ankle Society hallux
      MTP-IP scores and complications were evaluated as clinical assessments. The mean
      follow-up period was 43.3 weeks (range = 12-144). RESULTS: There were no
      significant differences in the amount and direction of movement of the fibular
      sesamoid between the LSTR group and non-LSTR group (1.9 mm and 1.6 mm,
      respectively) (P = .23). The direction was close to the second metatarsal bone in
      both groups. The complication rate in the LSTR group was 7.8% (n = 4) and 2.9% (n
      = 2) in the non-LSTR group (P = .40). CONCLUSIONS: Although there were
      significantly improved clinical and radiologic outcomes after surgery, the LSTR
      procedure did not result in medial shift or reduction of the sesamoid position.
      LEVEL OF EVIDENCE: Level III, retrospective case control study.

PMID- 26208510
TI  - From the Editor-in-Chief.

PMID- 26208511
TI  - Geographical/Ecological Differentials in Insecticide-Treated Net Use among Under
      Five Children in Somolu Local Government Area, Lagos State.
AB  - Malaria control efforts currently lay emphasis on reducing transmission by
      limiting human-vector contact. More studies have been carried out on mosquito
      avoidance practices in the rural areas, leaving the urban areas understudied.
      This study was conducted to identify knowledge of malaria transmission and to
      investigate geographical/ecological differentials in the use of insecticide
      treated nets (ITNs) among caregivers of under-fives in Somolu Local Government
      Area, Lagos State. A household survey was conducted by interviewing 394 female
      caregivers of under-fives selected using the WHO Lot Quality Technique from
      communities stratified based on level of planning and drainage. The mean age of
      the respondents was 33.6 +/- 7.7 years. Malaria transmission was attributed
      mostly to mosquito bites in all strata: S1 (58.3%), S2 (56.1%) and S3 (61.4%).
      Mosquito net was mentioned as a preventive measure by: 59.3% (S1), 80.7% (S2) and
      64.3% (S3). Ownership of long-lasting insecticidal nets was: 76.0% (S1), 75.4%
      (S2) and 68.6% (S3), and of these, 73.1% (S1), 70.7% (S2) and 72.4% (S3) reported
      that their child slept under the net the night before the survey. There is a need
      to reinforce education on transmission and ownership of ITNs especially among
      caregivers in unplanned, poorly drained communities. 

PMID- 26208512
TI  - Socioeconomic Determinants of Adult Mortality in Namibia Using an Event History
      Analysis.
AB  - Adult mortality remains a neglected public health issue in sub-Saharan Africa,
      with most policy instruments concentrated on child and maternal health. In
      developed countries, adult mortality is negatively associated with socioeconomic
      factors. A similar pattern is expected in developing countries, but has not been
      extensively demonstrated, because of dearth of data. Understanding the hazard and
      factors associated with adult mortality is crucial for informing policies and for
      implementation of interventions aimed at improving adult survival. This paper
      applied a geo-additive survival model to elucidate effects of socioeconomic
      factors on adult mortality in Namibia, controlling for spatial frailties. Results
      show a clear disadvantage for adults in rural areas, for those not married and
      from poor households or in female-headed households. The hazard of adult
      mortality was highly variable with a 1.5-fold difference between areas, with
      highest hazard recorded in north eastern, central west and southern west parts of
      the country. The analysis emphasizes that, for Namibia to achieve its national
      development goals, targeted interventions should be aimed at poor-resourced
      adults, particularly in high-risk areas. 

PMID- 26208513
TI  - Social Conditions and Disability Related to the Mortality of Older People in
      Rural South Africa.
AB  - BACKGROUND: South Africa is experiencing a health and social transition including
      an ageing population and an HIV epidemic. We report mortality experience of an
      older rural South African population. METHODS: Individual survey data and longer
      term demographic data were used to describe factors associated with mortality.
      Individuals aged 50 years and over (n = 4085) answered a health and quality of
      life questionnaire in 2006 and were followed for 3 years thereafter. Additional
      vital events and socio-demographic data were extracted from the Agincourt Health
      and Demographic Surveillance System from 1993 to 2010, to provide longer-term
      trends in mortality. Cox regression analysis was used to determine factors
      related to survival. RESULTS: In 10 967 person-years of follow-up between August
      2006 and August 2009, 377 deaths occurred. Women had lower mortality {hazard
      ratio [HR] 0.35 [95% confidence interval (CI) 0.28-0.45]}. Higher mortality was
      associated with being single [HR 1.48 (95% CI 1.16-1.88)], having lower household
      assets score [HR 1.79 (95% CI 1.28-2.51)], reporting greater disability [HR 2.40
      (95% CI 1.68-3.42)] and poorer quality of life [HR 1.59 (95% CI 1.09-2.31)].
      There was higher mortality in those aged under 69 as compared with those 70 to 79
      years old. Census data and cause specific regression models confirmed that this
      was due to deaths from HIV/TB in the younger age group. CONCLUSIONS: Mortality
      due to HIV/TB is increasing in men, and to some extent women, aged over 50.
      Policy makers and practitioners should consider the needs of this growing and
      often overlooked group.

PMID- 26208514
TI  - Management of developmental speech and language disorders: Part 1.
AB  - The identification of developmental problems in a child's acquisition of speech,
      language and/or communication is a core activity in child surveillance. These are
      common difficulties with up to 15% of toddlers being 'late talkers' and 7% of
      children entering school with persisting impairments of their language
      development. These delays can confer disadvantages in the long term, adversely
      affecting language, cognition, academic attainment, behaviour and mental health.
      All children presenting with significant speech and language delay should be
      investigated with a comprehensive hearing assessment and be considered for speech
      and language therapy assessment. Socioeconomic adversity correlates with delayed
      language development. Clinical assessment should confirm that the presentation is
      definitely not acquired (see part 2) and will also guide whether the difficulty
      is primary, in which there are often familial patterns, or secondary, from a very
      wide range of aetiologies. Symptoms may be salient, such as the regression of
      communication in <3-year-olds which 'flags up' autism spectrum disorder. Further
      investigation will be informed from this clinical assessment, for example,
      genetic investigation for sex aneuploidies in enduring primary difficulties.
      Management of the speech and language difficulty itself is the realm of the
      speech and language therapist, who has an ever-increasing evidence-based choice
      of interventions. This should take place within a multidisciplinary team,
      particularly for children with more severe conditions who may benefit from
      individualised parental and educational supports.

PMID- 26208515
TI  - Constitution and in vivo test of micro-porous tubular scaffold for esophageal
      tissue engineering.
AB  - Current clinical techniques in treating long-gap esophageal defects often lead to
      complications and high morbidity. Aiming at long-gap synthetic esophageal
      substitute, we had synthesized a biodegradable copolymer, poly(L-lactide-co
      caprolactone) (PLLC), with low glass transition temperature. In this work, we
      developed a tubular PLLC porous scaffold using a self-designed tubular mold and
      thermal induced phase separation (TIPS) method. In order to enhance the
      interaction between tissue and scaffold, fibrin, a natural fibrous protein
      derived from blood fibrinogen, was coated on the scaffold circumferential
      surface. The fibrin density was measured to be 1.23 +/- 0.04 mg/cm(2). Primary
      epithelial cell culture demonstrated the improved in vitro biocompatibility. In
      animal study with partial scaffold implantation, in situ mucosa regeneration was
      observed along the degradation of the scaffold. These indicate that fibrin
      incorporated PLLC scaffold can greatly improve epithelial regeneration in
      esophagus repair, therefore serve as a good candidate for long-term evaluation of
      post-implantation at excision site.

PMID- 26208516
TI  - Detection of aneurysmal subarachnoid hemorrhage 3 months after initial bleeding:
      evaluation of T2* and FLAIR MR sequences at 3 T in comparison with initial non
      enhanced CT as a gold standard.
AB  - OBJECTIVE: To investigate the ability of T2* and fluid-attenuated inversion
      recovery (FLAIR) MR sequences to detect hemosiderin deposition 3 months after
      aneurysmal subarachnoid hemorrhage (SAH) in comparison with early non-enhanced CT
      (NECT) as a gold standard. MATERIALS AND METHODS: From September 2008 through May
      2013, patients with aneurysmal SAH were included if a NECT less than 24 h after
      the onset of symptoms showed a SAH, and MRI, including T2* and FLAIR sequences,
      was performed 3 months later. All aneurysms were treated endovascularly. NECT and
      MR sequences were blindly analyzed for the presence of SAH (NECT) or hemosiderin
      deposition (MRI). When positive, details of the spatial distribution of SAH or
      hemosiderin deposits were noted. Sensitivities were calculated for each patient.
      Sensitivities, specificities, and positive predictive values (PPVs) were
      calculated for each location. RESULTS: Forty-nine patients (mean age 52.9 years)
      were included. Bleeding-related patterns were identified in 43 patients (87.8%)
      on T2* and 10 patients (20.4%) on FLAIR. T2* was highly predictive of the
      location of the initial hemorrhage, especially in the Sylvian cisterns (PPVs 95%
      and 100%) and the anterior interhemispheric fissure (PPV 90%). CONCLUSIONS: The
      T2* sequence can detect and localize a previous SAH a few months after aneurysmal
      bleeding.

PMID- 26208517
TI  - How to read a forest plot in a meta-analysis.

PMID- 26208518
TI  - Use of carbonated water in reduction of adjacent gastric activity in 456
      consecutive technetium-99m myocardial perfusion imaging studies.
AB  - BACKGROUND: Small, observational trials have suggested a reduction in adjacent
      gastric activity with ingestion of soda water in myocardial perfusion imaging
      (MPI). We report our findings prior to and after implementation of soda water in
      467 consecutive MPI studies. METHODS: Consecutive MPI studies performed at a high
      volume facility referred for vasodilator (VD) or exercise treadmill testing (ETT)
      were retrospectively reviewed before and after implementation of the soda water
      protocol. Patients undergoing the soda water protocol received 100 ml of soda
      water administered 30 min prior to image acquisition and after stress. Studies
      were performed using a same day rest/stress protocol. Incidence of adjacent
      gastric activity, diaphragmatic attenuation, stress and rest perfusion defects,
      and major adverse cardiovascular events (MACE) outcomes defined as death,
      myocardial infarction, stroke, reevaluation for chest pain, and late
      revascularization (>90 days from MPI) were abstracted using International
      Classification of Diseases, Ninth Revision (ICD-9) search. RESULTS: Two hundred
      and eighteen studies were performed prior to implementation of the soda water
      protocol and 249 studies were performed with the use of soda water. Baseline
      demographic data were equal between the groups with the exception of more
      patients undergoing VD stress receiving soda water (p < 0.001). Soda water was
      not associated with a decreased incidence of adjacent gastric activity with
      stress (54.7% versus 61.9% with no soda water, p = 0.129) or rest (68.6% versus
      69.5% with no soda water, p = 0.919) imaging. Less adjacent gastric activity was
      observed with patients undergoing ETT who received soda water (42.5% versus 56.9%
      with no soda water, p = 0.031), but no difference was observed between the groups
      with VD stress (69.0% versus 68.1% with no soda water, p = 1.000). CONCLUSION:
      The use of soda water prior to technetium-99m MPI was associated with lower rates
      of adjacent gastric activity only in patients undergoing ETT stress but not rest
      or VD stress. This differs from previously published data.

PMID- 26208519
TI  - Monitoring brain development of chick embryos in vivo using 3.0 T MRI:
      subdivision volume change and preliminary structural quantification using DTI.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has many advantages in the research
      of in vivo embryonic brain development, specifically its noninvasive aspects and
      ability to avoid skeletal interference. However, few studies have focused on
      brain development in chick, which is a traditional animal model in developmental
      biology. We aimed to serially monitor chick embryo brain development in vivo
      using 3.0 T MRI. METHODS: Ten fertile Hy-line white eggs were incubated and seven
      chick embryo brains were monitored in vivo and analyzed serially from 5 to 20
      days during incubation using 3.0 T MRI. A fast positioning sequence was pre
      scanned to obtain sagittal and coronal brain planes corresponding to the
      established atlas. T2-weighted imaging (T2WI) was performed for volume estimation
      of the whole brain and subdivision (telencephalon, cerebellum, brainstem, and
      lateral ventricle [LV]); diffusion tensor imaging (DTI) was used to reflect the
      evolution of neural bundle structures. RESULTS: The chick embryos' whole brain
      and subdivision grew non-linearly over time; the DTI fractional anisotropy (FA)
      value within the telencephalon increased non-linearly as well. All seven scanned
      eggs hatched successfully. CONCLUSIONS: MRI avoids embryonic sacrifice in a way
      that allows serial monitoring of longitudinal developmental processes of a single
      embryo. Feasibility for analyzing subdivision of the brain during development,
      and adding structural information related to neural bundles, makes MRI a powerful
      tool for exploring brain development.

PMID- 26208520
TI  - Nucleosome repeat lengths and columnar chromatin structure.
AB  - Thorough quantitative study of nucleosome repeat length (NRL) distributions,
      conducted in 1992 by J. Widom, resulted in a striking observation that the linker
      lengths between the nucleosomes are quantized. Comparison of the NRL average
      values with the MNase cut distances predicted from the hypothetical columnar
      structure of chromatin (this work) shows a close correspondence between the two.
      This strongly suggests that the NRL distribution, actually, reflects the dominant
      role of columnar chromatin structure common for all eukaryotes. 

PMID- 26208521
TI  - Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian
      perspective.
AB  - This review tackles the issues related to disease burden caused by cervical
      cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given
      to new technologies with potential to interfere with the development of CC by
      reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain
      a major public health burden in all developing countries where organized
      screening programs do not exist. Globally, 85% of all incident CC and 50% of CC
      deaths occur in the developing countries. Unfortunately, most regions of Brazil
      still demonstrate high mortality rates, ranking CC as the second most common
      cancer among Brazilian women. Recently, CC screening programs have been tailored
      in the country to enable early detection of CC precursor lesions and thereby
      reduce cancer mortality. A combination of HPV testing with liquid-based cytology
      (LBC) seems to be a promising new approach in CC screening, with high expectation
      to offer an adequate control of CC burden in this country.

PMID- 26208522
TI  - PKCiota depletion initiates mitotic slippage-induced senescence in glioblastoma.
AB  - Cellular senescence is a tumor suppressor mechanism where cells enter a permanent
      growth arrest following cellular stress. Oncogene-induced senescence (OIS) is
      induced in non-malignant cells following the expression of an oncogene or
      inactivation of a tumor suppressor. Previously, we have shown that protein kinase
      C iota (PKCiota) depletion induces cellular senescence in glioblastoma cells in
      the absence of a detectable DNA damage response. Here we demonstrate that
      senescent glioblastoma cells exhibit an aberrant centrosome morphology. This was
      observed in basal levels of senescence, in p21-induced senescence, and in PKCiota
      depletion-induced senescence. In addition, senescent glioblastoma cells are
      polyploid, Ki-67 negative and arrest at the G1/S checkpoint, as determined by
      expression of cell cycle regulatory proteins. These markers are all consistent
      with cells that have undergone mitotic slippage. Failure of the spindle assembly
      checkpoint to function properly can lead to mitotic slippage, resulting in the
      premature exit of mitotic cells into the G1 phase of the cell cycle. Although in
      G1, these cells have the replicated DNA and centrosomal phenotype of a cell that
      has entered mitosis and failed to divide. Overall, we demonstrate that PKCiota
      depletion initiates mitotic slippage-induced senescence in glioblastoma cells. To
      our knowledge, this is the first evidence of markers of mitotic slippage directly
      in senescent cells by co-staining for senescence-associated beta-galactosidase
      and immunofluorescence markers in the same cell population. We suggest that
      markers of mitotic slippage be assessed in future studies of senescence to
      determine the extent of mitotic slippage in the induction of cellular senescence.

PMID- 26208523
TI  - The 1,2-Diaminocyclohexane Carrier Ligand in Oxaliplatin Induces p53-Dependent
      Transcriptional Repression of Factors Involved in Thymidylate Biosynthesis.
AB  - Platinum-based chemotherapeutic drugs are widely used as components of
      combination chemotherapy in the treatment of cancer. One such drug, oxaliplatin,
      exerts a synergistic effect against advanced colorectal cancer in combination
      with 5-fluorouracil (5-FU) and leucovorin. In the p53-proficient colorectal
      cancer cell line HCT116, oxaliplatin represses the expression of deoxyuridine
      triphosphatase (dUTPase), a ubiquitous pyrophosphatase that catalyzes the
      hydrolysis of dUTP to dUMP and inhibits dUTP-mediated cytotoxicity. However, the
      underlying mechanism of this activity has not been completely elucidated, and it
      remains unclear whether factors other than downregulation of dUTPase contribute
      to the synergistic effect of 5-FU and oxaliplatin. In this study, we found that
      oxaliplatin and dachplatin, platinum-based drugs containing the 1,2
      diaminocyclohexane (DACH) carrier ligand, repressed the expression of nuclear
      isoform of dUTPase (DUT-N), whereas cisplatin and carboplatin did not.
      Oxaliplatin induced early p53 accumulation, upregulation of primary miR-34a
      transcript expression, and subsequent downregulation of E2F3 and E2F1. Nutlin-3a,
      which activates p53 nongenotoxically, had similar effects. Introduction of miR
      34a mimic also repressed E2F1 and DUT-N expression, indicating that this miRNA
      plays a causative role. In addition to DUT-N, oxaliplatin repressed, in a p53
      dependent manner, the expression of genes encoding enzymes involved in
      thymidylate biosynthesis. Consequently, oxaliplatin significantly decreased the
      level of dTTP in the dNTP pool in a p53-dependent manner. These data indicate
      that the DACH carrier ligand in oxaliplatin triggers signaling via the p53-miR
      34a-E2F axis, leading to transcriptional regulation that ultimately results in
      accumulation of dUTP and reduced dTTP biosynthesis, potentially enhancing 5-FU
      cytotoxicity.

PMID- 26208524
TI  - BGB-283, a Novel RAF Kinase and EGFR Inhibitor, Displays Potent Antitumor
      Activity in BRAF-Mutated Colorectal Cancers.
AB  - Oncogenic BRAF, which drives cell transformation and proliferation, has been
      detected in approximately 50% of human malignant melanomas and 5% to 15% of
      colorectal cancers. Despite the remarkable clinical activities achieved by
      vemurafenib and dabrafenib in treating BRAF(V600E) metastatic melanoma, their
      clinical efficacy in BRAF(V600E) colorectal cancer is far less impressive. Prior
      studies suggested that feedback activation of EGFR and MAPK signaling upon BRAF
      inhibition might contribute to the relative unresponsiveness of colorectal cancer
      to the first-generation BRAF inhibitors. Here, we report characterization of a
      dual RAF kinase/EGFR inhibitor, BGB-283, which is currently under clinical
      investigation. In vitro, BGB-283 potently inhibits BRAF(V600E)-activated ERK
      phosphorylation and cell proliferation. It demonstrates selective cytotoxicity
      and preferentially inhibits proliferation of cancer cells harboring BRAF(V600E)
      and EGFR mutation/amplification. In BRAF(V600E) colorectal cancer cell lines, BGB
      283 effectively inhibits the reactivation of EGFR and EGFR-mediated cell
      proliferation. In vivo, BGB-283 treatment leads to dose-dependent tumor growth
      inhibition accompanied by partial and complete tumor regressions in both cell
      line-derived and primary human colorectal tumor xenografts bearing BRAF(V600E)
      mutation. These findings support BGB-283 as a potent antitumor drug candidate
      with clinical potential for treating colorectal cancer harboring BRAF(V600E)
      mutation.

PMID- 26208526
TI  - Hannelore Wass as a Teacher.
AB  - As an educator, Hannelore Wass had a major influence on young professionals who
      were teaching in the field of thanatology. She influenced new professors by
      mentoring and providing an exceptional example of a compassionate, competent
      professional in the fields of thanatology and educational methodology. As a
      strong advocate for death education for all ages, Hannelore was a supporter of
      death educators. Her books provided a solid knowledge base in dying, death, and
      bereavement and thereby helped professionals learn the body of information in
      thanatology. 

PMID- 26208525
TI  - Antitumor Activity and Acquired Resistance Mechanism of Dovitinib (TKI258) in RET
      Rearranged Lung Adenocarcinoma.
AB  - RET rearrangement is a newly identified oncogenic mutation in lung adenocarcinoma
      (LADC). Activity of dovitinib (TKI258), a potent inhibitor of FGFR, VEGFR, and
      PDGFR, in RET-rearranged LADC has not been reported. The aims of the study are to
      explore antitumor effects and mechanisms of acquired resistance of dovitinib in
      RET-rearranged LADC. Using structural modeling and in vitro analysis, we
      demonstrated that dovitinib induced cell-cycle arrest at G0-G1 phase and
      apoptosis by selective inhibition of RET kinase activity and ERK1/2 signaling in
      RET-rearranged LC-2/ad cells. Strong antitumor effect of dovitinib was observed
      in an LC-2/ad tumor xenograft model. To identify the acquired resistance
      mechanisms to dovitinib, LC-2/ad cells were exposed to increasing concentrations
      of dovitinib to generate LC-2/ad DR cells. Gene-set enrichment analysis of gene
      expression and phosphor-kinase revealed that Src, a central gene in focal
      adhesion, was activated in LC-2/ad DR cells. Saracatinib, an src kinase
      inhibitor, suppressed ERK1/2 phosphorylation and growth of LC-2/ad DR cells.
      Taken together, these findings suggest that dovitinib can be a potential
      therapeutic option for RET-rearranged LADC, in which acquired resistance to
      dovitinib can be overcome by targeting Src.

PMID- 26208527
TI  - Potassium sensitivity differs among strains of the harmful cyanobacterium
      Microcystis and correlates with the presence of salt tolerance genes.
AB  - Microcystis aeruginosa is a ubiquitous harmful cyanobacterium that causes
      problems in eutrophic lakes. Potassium ion (K(+)) addition is one of the
      suggested methods to combat harmful cyanobacterial blooms. To investigate the
      effectiveness of this method, we compared the potassium ion sensitivity of four
      Microcystis strains. Microcystis strains PCC 7005 and NIES-843 were very
      susceptible to potassium ion concentrations of ~ 12 mmol L(-1), whereas strain
      PCC 7806 and its non-toxic mutant PCC 7806 DeltamcyB were not affected by added
      potassium ions. The origin of the strain appears to be of importance. Strain PCC
      7806 originates from brackish water and possesses genes for the synthesis of the
      compatible solute sucrose, the water channel protein gene aqpZ and the sodium
      influx gene nhaS2, whereas strains PCC 7005 and NIES-843 have a freshwater origin
      and lack these genes. We conclude that potassium ion addition will not be a
      successful mitigation strategy in brackish waters, but may temporarily suppress
      Microcystis blooms in freshwater lakes. However, in the long run other
      Microcystis strains or other cyanobacteria with a higher salt tolerance will
      likely take over. In addition, our results also have implications for the
      potassium ion concentrations of mineral media used in laboratory studies with
      cyanobacteria.

PMID- 26208528
TI  - The relationship between biofilm and outer membrane vesicles: a novel therapy
      overview.
AB  - Microorganisms have the ability of inhabiting nearly every environment through
      their sophisticated mechanisms of survival such as biofilm formation and release
      of outer membrane vesicles (OMVs). The biofilm matrix offers microorganism
      protection and contributes significantly to several clinical challenges,
      including symptomatic inflammation, antibiotic resistance, recurrence and the
      spread of infectious emboli. Moreover, bacteria also have another protective
      mechanism of vesicle production which is used as a means of disseminating toxins
      to harm their host. A clear understanding of gene expression switch of bacterium
      from planktonic to biofilm mode offers clinical potentials in treating bacterial
      infections. In this respect, the treatment of bacterial infections may be
      achieved through (1) application of RNA interference technology to silence the
      expression of proteins involved in the process of biofilm formation, (2)
      utilization of vesicles in delivering antibiotics and (3) use of natural occurred
      compounds. In this review, we discuss the relationship between biofilm formation
      and OMV production with respect to tackling biofilm-related clinical challenges.
      Some prospective considerations in biofilm-associated infections treatment are
      also discussed. 

PMID- 26208529
TI  - Biofilm formation by Borrelia burgdorferi sensu lato.
AB  - Bacterial biofilms are microbial communities held together by an extracellular
      polymeric substance matrix predominantly composed of polysaccharides, proteins
      and nucleic acids. We had previously shown that Borrelia burgdorferi sensu
      stricto, the causative organism of Lyme disease in the United States is capable
      of forming biofilms in vitro. Here, we investigated biofilm formation by B.
      afzelii and B. garinii, which cause Lyme disease in Europe. Using various
      histochemistry and microscopy techniques, we show that B. afzelii and B. garinii
      form biofilms, which resemble biofilms formed by B. burgdorferi sensu stricto.
      High-resolution atomic force microscopy revealed similarities in the
      ultrastructural organization of the biofilms form by three Borrelia species.
      Histochemical experiments revealed a heterogeneous organization of
      exopolysaccharides among the three Borrelia species. These results suggest that
      biofilm formation might be a common trait of Borrelia genera physiology. 

PMID- 26208530
TI  - Prebiotics and gut microbiota in chickens.
AB  - Prebiotics are non-digestible feed ingredients that are metabolized by specific
      members of intestinal microbiota and provide health benefits for the host.
      Fermentable oligosaccharides are best known prebiotics that have received
      increasing attention in poultry production. They act through diverse mechanisms,
      such as providing nutrients, preventing pathogen adhesion to host cells,
      interacting with host immune systems and affecting gut morphological structure,
      all presumably through modulation of intestinal microbiota. Currently,
      fructooligosaccharides, inulin and mannanoligosaccharides have shown promising
      results while other prebiotic candidates such as xylooligosaccharides are still
      at an early development stage. Despite a growing body of evidence reporting
      health benefits of prebiotics in chickens, very limited studies have been
      conducted to directly link health improvements to prebiotic-dependent changes in
      the gut microbiota. This article visits the current knowledge of the chicken
      gastrointestinal microbiota and reviews most recent publications related to the
      roles played by prebiotics in modulation of the gut microbiota and immune
      functions. Progress in this field will help us better understand how the gut
      microbiota contributes to poultry health and productivity, and support the
      development of new prebiotic products as an alternative to in-feed antibiotics. 

PMID- 26208531
TI  - Synthesis of cryptocrystalline magnesite/bentonite clay composite and its
      application for removal of phosphate from municipal wastewaters.
AB  - In the present study, nanocomposite of cryptocrystalline magnesite-bentonite clay
      was used as a novel technology for removal of phosphates from municipal
      effluents. Vibratory ball miller was used for fabrication of the composite.
      Removal of phosphate from an aqueous solution was achieved using batch
      experimental procedures. The parameters optimized include time, dosage,
      concentration and pH. An optimization experiment revealed that 30 mins of shaking
      time, 1 g of composite, 100 mg L(-1) of phosphate, 1: 100 S/L ratios, 250 rpm, pH
      10 and room temperature are the optimum conditions for removal of phosphate.
      Adsorption data fitted well to the Langmuir adsorption isotherm than Freundlich
      adsorption isotherms, thus confirming monolayer adsorption. Adsorption kinetics
      data fitted well to pseudo second-order kinetics than first-order kinetics, thus
      suggesting chemisorption. This comparative study showed better adsorption of the
      composite as compared to conventional methods of phosphate removal. The results
      suggest that the fabricated composite has the potential for remediation of
      phosphate-contaminated waters. 

PMID- 26208532
TI  - Multimodality imaging of bilateral pheochromocytoma. A case report.
AB  - INTRODUCTION: Bilateral pheochromocytomas ( PHEO ) are rare, often hereditary and
      linked to a germline mutation of RET, VHL or SDHx. They also occur sporadically.
      PRESENTATION OF CASE: We report a case of a 76 year old female hospitalized for
      biological investigations following symptoms of abdominal discomfort with
      recurrent hypertensive episodes. The hormonal work up results favoured a
      diagnosis of a PHEO (urinary and plasma metanephrines > 10 times normal).
      Radiological investigations (CT-MRI): identified bilateral adrenal masses (47 mm
      in the right adrenal, 26 mm in the left adrenal). Functional imaging with 123 I
      MIBG scintigraphy showed intense uptake in the right adrenal mass with limited
      uptake in the left, probably related to a fixation of the normal adrenal medulla.
      Due to the strong suspicion of bilateral PHEO, further imaging with an 18F-FDOPA
      PET was performed. This revealed intense hypermetabolism of the right mass but
      the left mass had similar metabolism to the liver, thought to be unsuspicious for
      a PHEO. It was decided to proceed with a laparoscopic right adrenalectomy.
      Hormonal investigations performed post-operatively revealed persistently elevated
      metanephrines. An 18FFDG PET was performed, revealing an intense hypermetabolic
      focus in the left adrenal gland. A laparoscopic partial left adrenalectomy was
      subsequently performed 6 weeks after the initial right adrenalectomy. DISCUSSION
      AND CONCLUSIONS: This case highlights the possibility of false negative results
      using specific functional imaging. In these situations, 18F-FDG PET may be
      useful. The MRI signal has an indisputable value. Until today, no germline
      mutation was found in this patient.

PMID- 26208533
TI  - Effect of different number of players and training regimes on physiological and
      technical demands of ball-drills in basketball.
AB  - This study aimed to analyse the effects of two factors (number of players and
      training regimes) on players' physiological and technical demands in basketball
      ball-drills. Twenty-one young basketball players performed four different ball
      drills (two levels for each factor). The number of players involved was 2vs2 and
      4vs4, while ball-drill regimes were continuous and intermittent. Physiological
      demand was assessed using the percentage of maximal heart rate (%HRmax), Edwards'
      training load and rating of perceived exertion (RPE). Furthermore, the following
      technical actions were collected: dribbles, steals, rebounds, turnovers, passes
      (total, correct, wrong and % of correct pass) and shots (total, scored, missed
      and % of made shot). A 2 * 2 (number of players * regime) two-way ANOVA with
      repeated measures was applied for physiological parameters and technical actions.
      The 2vs2 condition showed higher %HRmax (P < 0.001), Edwards' training load (P <
      0.001), RPE (P < 0.001), number of dribbles (P < 0.001), rebounds (P < 0.001),
      passes [total (P = 0.005) and correct (P = 0.005)] and shots [total (P < 0.001)
      scored (P < 0.001) and missed (P < 0.001)] than 4vs4. Moreover, the continuous
      regime revealed higher %HRmax (P < 0.001), Edwards' training load (P < 0.001),
      RPE (P = 0.006) and dribbles (P < 0.001) than the intermittent regime. This study
      showed that both number of players and regime are useful variables able to modify
      basketball ball-drills workload. 

PMID- 26208534
TI  - Trait worry is associated with difficulties in working memory updating.
AB  - The current study investigated the effects of trait worry, a subcomponent of
      trait anxiety, on the process of updating information in working memory (WM). A
      leading theory on anxiety and executive functions, attentional control theory
      (ACT), states that anxiety is not related to WM updating in emotionally neutral
      situations. Previous research, however, has focused almost exclusively on WM span
      tasks that primarily emphasised storage, rather than the updating of WM
      representations. Moreover, few studies have directly examined the effects of
      trait worry. In this study, 116 subjects performed a WM updating task that
      required the memorisation of short lists of words and the within-trial removal of
      some of these items from WM. Results indicated that levels of trait worry were
      not related to word-span performance, but were related to performance on trials
      that required subjects to effectively update WM. Moreover, these effects were
      observed only for trait worry, not for levels of anxious arousal or comorbid
      levels of dysphoria. These results support the hypothesis that trait worry is
      related to WM updating performance and thereby extend ACT in new directions.

PMID- 26208535
TI  - Psychometric properties of the AHRQ Community Pharmacy Survey on Patient Safety
      Culture: a factor analysis.
AB  - BACKGROUND: The U.S. Agency for Healthcare Research and Quality (AHRQ) developed
      a hospital patient safety culture survey in 2004 and has adapted this survey to
      other healthcare settings, such as nursing homes and medical offices, and most
      recently, community pharmacies. However, it is unknown whether safety culture
      dimensions developed for hospitals can be transferred to community pharmacies.
      The aim of this study was to assess the psychometric properties of the Community
      Pharmacy Survey on Patient Safety Culture. METHOD: The survey was administered to
      543 community pharmacists in Wisconsin, USA. Confirmatory factor analysis was
      used to assess the fit of our data with the proposed AHRQ model. Exploratory
      factor analysis was used to determine the underlying factor structure. Internal
      consistency reliabilities were calculated. RESULTS: A total of 433 usable surveys
      were returned (response rate 80%). Results from the confirmatory factor analysis
      showed inadequate model fit for the original 36 item, 11-factor structure.
      Exploratory factor analysis showed that a modified 27-item, four-factor structure
      better reflected the underlying safety culture dimensions in community
      pharmacies. The communication openness factor, with three items, dropped in its
      entirety while six items dropped from multiple factors. The remaining 27 items
      redistributed to form the four-factor structure: safety-related communication,
      staff training and work environment, organisational response to safety events,
      and staffing, work pressure and pace. Cronbach's alpha of 0.95 suggested good
      internal consistency. CONCLUSIONS: Our findings suggest that validation studies
      need to be conducted before applying safety dimensions from other healthcare
      settings into community pharmacies.

PMID- 26208536
TI  - Safety culture in long-term care: a cross-sectional analysis of the Safety
      Attitudes Questionnaire in nursing and residential homes in the Netherlands.
AB  - OBJECTIVE: The first objective was to investigate if the Safety Attitudes
      Questionnaire (SAQ) is appropriate to measure the safety attitude of caregivers
      in nursing and residential homes, and second, to compare safety attitude of these
      caregivers with available data of caregivers in other settings (ie, inpatients,
      intensive care unit (ICU) and ambulatory care). METHODS: Using a cross-sectional
      survey methodology, we obtained completed SAQ surveys from 521 caregivers
      (response rate of 53%) working in nine units in nine different nursing and
      residential homes in The Netherlands. Exploratory factor and Cronbach's alpha
      measures were used to analyse the psychometric properties of the SAQ. A
      correlation matrix was performed to study the relationship among the SAQ
      dimensions. A t test was performed to test significant differences between our
      sample and the benchmark settings. RESULTS: The factor analyses and calculated
      Cronbach's alphas (alpha=0.56-0.80) for this sample confirmed the robustness of
      the SAQ scales. There was a high positive correlation between teamwork climate,
      job satisfaction, perceptions of management, safety climate and working
      conditions (r=0.31 to 63), but stress recognition had a negative correlation with
      each of the other dimensions (r=-0.13 to -0.18). Overall, the scores from the
      nursing and residential homes differed significantly from the benchmark settings.
      CONCLUSIONS: The findings in this study confirmed that the SAQ could also be used
      in the nursing and residential homes setting. However, stress recognition in
      nursing and residential homes setting does not seem to be one of the dimensions
      of the safety attitude construct. Furthermore, Dutch nursing and residential
      homes have significantly higher scores on most dimensions of the SAQ compared
      with US inpatient units and comparable scores to ICUs (Dutch and US) and
      ambulatory services.

PMID- 26208537
TI  - Implementation of HIV treatment as prevention strategy in 17 Canadian sites:
      immediate and sustained outcomes from a 35-month Quality Improvement
      Collaborative.
AB  - BACKGROUND: Rapid scale-up of effective antiretroviral therapy (ART) is required
      to meet global targets to eliminate new HIV infections and AIDS-related deaths.
      Yet, gaps persist in all nations striving for these targets. In the intervention
      setting of British Columbia (BC), Canada, where ART is publicly funded, 73% of
      HIV-diagnosed were on ART in 2011, and only 49% were achieving viral suppression.
      METHODS: An observational case descriptive study of HIV care sites in BC
      recruited to participate in a 35-month Breakthrough Series Quality Improvement
      Collaborative and sustainability network. Sites collected four quality
      indicators, qualitative change descriptions and implemented the chronic care
      model (CCM) and HIV care and treatment guidelines. Two reviewers assigned monthly
      implementation scores to evaluate site progress (January 2011-2012). All quality
      indicators were pooled and analysed using probability-based run chart rules.
      RESULTS: Seventeen teams with a pooled median population of 2296 HIV patients
      joined the initiative. Comprehensive CCM implementation and evidence of
      improvement was achieved by 29% of sites (implementation score of 4.0 or higher
      on 5.0 scale). Evidence of sustained improvement was observed for patient
      engagement (88.8-90.4%), ART uptake among patients unequivocally in need (92.9
      94.8%), and ART uptake (>=6 months) and achieving viral suppression (57.3-78.4%)
      (all p<0.05). CONCLUSIONS: This study shows evidence of sustained improvements in
      HIV care processes and treatment outcomes for an estimated population of 2296 HIV
      patients in 17 BC sites. Overall success points to opportunities for other high
      income countries seeking to improve HIV health outcomes.

PMID- 26208538
TI  - What do patients say about emergency departments in online reviews? A qualitative
      study.
AB  - BACKGROUND: Patients have adopted web-based tools to report on the quality of
      their healthcare experiences. We seek to examine online reviews for US emergency
      departments (EDs) posted on Yelp, a popular consumer ratings website. METHODS: We
      conducted a qualitative analysis of unstructured, publicly accessible reviews for
      hospitals available on http://www.yelp.com. We collected all reviews describing
      experiences of ED care for a stratified random sample of 100 US hospitals. We
      analysed the content of the reviews using themes derived from the Hospital
      Consumer Assessment of Healthcare Providers and Systems (HCAHPS) inpatient care
      survey. We also used modified grounded theory to iteratively code the text of the
      reviews, identifying additional themes specific to emergency care. The data were
      double-coded, and discrepancies were evaluated to ensure consensus. RESULTS: Of
      the 1736 total reviews, 573 (33%) described patient experiences involving the ED.
      The reviews contained several themes assessed by the HCAHPS survey, including
      communication with nurses, communication with doctors, and pain control. The
      reviews also contained key themes specific to emergency care: waiting and
      efficiency; decisions to seek care in the ED; and events following discharge,
      including administrative difficulties. CONCLUSIONS: These exploratory findings
      suggest that online reviews for EDs contain similar themes to survey-based
      assessments of inpatient hospital care as well as themes specific to emergency
      care. Consumer rating websites allow patients to provide rapid and public
      feedback on their experience of medical care. Web-based platforms may offer a
      novel strategy for assessing patient-centred quality in emergency care.

PMID- 26208539
TI  - Reducing hospital noise with sound acoustic panels and diffusion: a controlled
      study.

PMID- 26208540
TI  - Investigation of flap flexibility of beta-secretase using molecular dynamic
      simulations.
AB  - Flap motif and its dynamics were extensively reported in aspartate proteases,
      e.g. HIV proteases and plasmepsins. Herein, we report the first account of flap
      dynamics amongst different conformations of beta-secretase using molecular
      dynamics simulation. Various parameters were proposed and a selected few were
      picked which could appropriately describe the flap motion. Three systems were
      studied, namely Free (BACEFree) and two ligand-bound conformations, which
      belonged to space groups P6122 (BACEBound1) and C2221 (BACEBound2), respectively
      and four parameters (distance between the flaps tip residue, Thr72 and Ser325,
      d1; dihedral angle, phi (Thr72-Asp32-Asp228-Ser325); TriCalpha angles, theta1
      (Thr72-Asp32-Ser325), and theta2 (Thr72-Asp228-Ser325)) were proposed to
      understand the change in dynamics of flap domain and the extent of flap opening
      and closing. Analysis of, theta2, d1, theta1 and phi confirmed that the BACEFree
      adopted semi-open, open and closed conformations with slight twisting during flap
      opening. However, BACEBound1 (P6122) showed an adaptation to open conformation
      due to lack of hydrogen bond interaction between the ligand and flap tip residue.
      A slight flap twisting, phi (lateral twisting) was observed for BACEBound1 during
      flap opening which correlates with the opening of BACEFree. Contradictory to the
      BACEBound1, the BACEBound2 locked the flap in a closed conformation throughout
      the simulation due to formation of a stable hydrogen bond interaction between the
      flap tip residue and ligand. Analyses of all three systems highlight that d1,
      theta2 and phi can be precisely used to describe the extent of flap opening and
      closing concurrently with snapshots along the molecular dynamics trajectory
      across several conformations of beta-secretase. 

PMID- 26208541
TI  - The EDTA Amendment in Phytoextraction of (134)Cs From Soil by Indian Mustard
      (Brassica juncea).
AB  - Soil contamination with radiocaesium is a significant problem at any countries
      when a nuclear accident occurred. Recently, phytoextraction technique is
      developed to remediate the contaminated environment. However, the application is
      limited by the availability of the contaminant for root uptake. Therefore, a
      green house trial experiment of soil amendment with ethylene diamine tetraacetic
      acid (EDTA) has been conducted to examine (134)Cs availability for root uptake.
      Two groups of Indian mustard (Brassica juncea) were cultivated in (134)Cs
      contaminated soil. The soil in the first group was treated with EDTA amendment,
      while the other was not. Plant growth was observed gravimetrically and the
      (134)Cs concentration in soil as well as plants were determined using gamma
      spectrometry. The plant uptake capacity was determined as transfer factor (Fv),
      and the Fv values of 0.22 +/- 0.0786 and 0.12 +/- 0.039 were obtained for the
      soil treated with and without EDTA amendment, respectively. The phytoextraction
      efficiency of the plant cultivated in (134)Cs contaminated soil both with and
      without EDTA amendment was low. The EDTA amendment to the soil seems to enhance
      the (134)Cs availability for root uptake of Indian mustard and can still be
      considered to assist the field phytoremediation of contaminated soil.

PMID- 26208542
TI  - Biosorption Behavior of Ciprofloxacin onto Enteromorpha prolifera: Isotherm and
      Kinetic Studies.
AB  - The studies aimed at the feasibility of using Enteromorpha prolifera for the
      removal of ciprofloxacin from aqueous solutions. Batch experiments were carried
      out for the biosorption of ciprofloxacin onto Enteromorpha prolifera. The factors
      affecting the biosorption process such as the initial concentration, dosage, pH
      and the contact time were studied. Enteromorpha prolifera exhibited a maximum
      biosorption capacity of 21.7 mg/g. The pseudo-second-order kinetic model
      described the ciprofloxacin biosorption process with a good fitting. The optimum
      pH of ciprofloxacin adsorbed by Enteromorpha prolifera was 10. Biosorption
      equilibrium studies demonstrated that the biosorption followed Freundlich
      isotherm model, which implied a heterogeneous biosorption phenomenon.

PMID- 26208543
TI  - Local Community Perceptions of Mine Site Restoration Using Phytoremediation in
      Abitibi-Temiscamingue (Quebec).
AB  - This work explores factors supporting people perception about mine site
      restoration and phytoremediation. Phytoremediation is one of the most eco
      friendly restoration strategy emerged since the last two decades but studies on
      local people perception on this restoration strategy are scarce. To fill in this
      gap, data were collected from mining stakeholders using a structured
      questionnaire administered through snowball sampling method. We used Multiple
      Correspondence Analysis as implemented in the software XLSTAT to visualize
      relationship between participants' characteristics, their view on mine site
      restoration and phytoremediation. Results clearly show out that people perception
      on mine site restoration is influenced by mining activities effects on health and
      region attractiveness. Phytoremediation (65.21%) was rated positively with regard
      to its environment potential, aesthetic and consideration for future generation
      followed by fillings and excavating. Restoration strategy costs have no effect on
      people choice and participants prefer use of shrubs as vegetation component of
      phytoremediation to reach their restoration objective.

PMID- 26208544
TI  - Rhizobacteria of Populus euphratica Promoting Plant Growth Against Heavy Metals.
AB  - The heavy metal-resistant bacteria from rhizospheric soils of wild Populus
      euphratica forest growing in arid and saline area of northwestern China were
      investigated by cultivation-dependent methods. After screening on medium sparked
      with zinc, copper, nickel and lead, 146 bacteria strains with different
      morphology were isolated and most of them were found to be resistant to at least
      two kinds of heavy metals. Significant increase in fresh weight and leaf surface
      area of Arabidopsis thaliana seedlings under metal stress were noticed after
      inoculated with strains especially those having multiple-resistance to heavy
      metals such as Phyllobacterium sp. strain C65. Investigation on relationship
      between auxin production and exogenous zinc concentration revealed that
      Phyllobacterium sp. strain C65 produced auxin, and production decreased as the
      concentration of zinc in medium increased. For wheat seedlings treated with zinc
      of 2 mM, zinc contents in roots of inoculated plants decreased by 27% (P < 0.05)
      compared to the uninoculated control. Meanwhile, zinc accumulation in the above
      ground tissues increased by 22% (P < 0.05). The translocation of zinc from root
      to above-ground tissues induced by Phyllobacterium sp. strain C65 helped host
      plants extract zinc from contaminated environments more efficiently thus
      alleviated the growth inhibition caused by heavy metals.

PMID- 26208545
TI  - [People in view, brain in focus].

PMID- 26208546
TI  - Disaster Planning and Impending Healthcare Challenges During Natural Disasters in
      Pakistan.

PMID- 26208547
TI  - Quality of Colonoscopy and Spectrum of Lower Gastrointestinal Disease as
      Determined by Colonoscopy.
AB  - OBJECTIVE: To document the quality of colonoscopy practice and the pattern of
      colonic disease including polyp detection rate at Shifa International Hospital,
      Islamabad, Pakistan. STUDY DESIGN: An observational study. PLACE AND DURATION OF
      STUDY: Shifa International Hospital, Islamabad, Pakistan, from May 2013 to June
      2014. METHODOLOGY: This retrospective study recorded demographics of patients,
      indications and quality indices of 505 colonoscopies performed during the study
      period. Preparation was done with low residue diet and polyethylene glycol.
      Conscious sedation was generally used. Quality indices studied were compared with
      guideline standard. RESULTS: Out of 505 colonoscopy patients, 305 were males and
      200 were females. The indications for colonoscopic examination were lower
      gastrointestinal bleeding (26.5%, n=134), screening for colorectal cancer (14.1%,
      n=71), chronic diarrhea (12.9%, n=65), abdominal pain (10.9%, n=55), anemia
      (9.1%, n=46), constipation (7.3%, n=37), hematochezia and diarrhea (6.3%, n=32),
      altered bowel habits (5.1%, n=26), weight loss (3.6%, n=18), colonic thickening
      on CT scan (3.0%, n=15) and others (1.2%, n=6). Bowel preparation was adequate
      (in 92%, n=465) cases. Cecal intubation rate was 88.71% (n=448). Endoscopic
      diagnoses were hemorrhoids (36.2%, n=183), normal (22%, n=111), polyps (11.3%,
      n=57), ulcerative colitis (8.7%, n=44), cancer (4%, n=20), diverticulosis (3.4%,
      n=17), infective colitis (2.6%, n=13), intestinal TB (2.6%, n=13), non-specific
      colitis (2.2%, n=11), proctitis (1.8%, n=9) and others (5.3%, n=27). CONCLUSION:
      There is room for improvement in quality of colonoscopy, cecal intubation rate is
      slightly below the recommended standard and polyp detection rate is quite low
      however, it is not clear if the low rate of polyp detection is due to missed
      lesions or low population incidence. Time to reach caecum and withdrawal time
      should clearly be documented in the notes which can help to evaluate quality of
      the procedure in a better way.

PMID- 26208548
TI  - Polymorphisms of the ABCB1 Gene in the Pakistani Population.
AB  - OBJECTIVE: To investigate the frequency of the single nucleotide polymorphism
      C1236T in exon 12 of the ABCB1 gene in Pakistani population and to compare it
      with published data on Asian and Caucasian populations. STUDY DESIGN: Across
      sectional observational study. PLACE AND DURATION OF STUDY: Combined Military
      Hospital, Rawalpindi and Institute of Biomedical and Genetic Engineering (IBGE),
      Islamabad, from August 2012 to May 2013. METHODOLOGY: C1236T polymorphism was
      investigated in 426 Pakistani subjects. The frequency was compared with the
      published data on other Asian and Caucasian populations. RESULTS: The frequencies
      of ABCB1 C1236T were 16.4% for CC, 44.1% for CT and 39.4% for TT. Pakistanis
      differed significantly from all the European populations compared in the
      distribution of the TT genotype of C1236TABCB1 (p < 0.05). The Pakistani
      population also differed significantly from some of the European populations in
      the distribution of CC and CT genotype (p < 0.05). CONCLUSION: There was
      significant difference in the genotype frequency of the ABCB1 gene compared to
      other populations. This study has provided a framework for future pharmacogenetic
      and pharmacokinetic studies on this polymorphic variant of ABCB1 gene in the
      Pakistani population.

PMID- 26208549
TI  - Association of Anti-Emetic Efficacy of Ondansetron with G2677T Polymorphism in a
      Drug Transporter Gene ABCB1 in Pakistani Population.
AB  - OBJECTIVE: To determine the association of ABCB1 polymorphism G2677T with anti
      emetic efficacy in patients treated with ondansetron for preventing postoperative
      nausea and vomiting. STUDY DESIGN: A clinical trial. PLACE AND DURATION OF STUDY:
      Combined Military Hospital, Rawalpindi and Institute of Biomedical and Genetic
      Engineering, Islamabad, from 2012 to 2013. METHODOLOGY: Four mg ondansetron was
      administered intravenously 30 minutes before the end of surgery. A total of 246
      patients with the complaints of nausea and vomiting and 244 patients without
      nausea and vomiting were analyzed for G2677T polymorphism using PCR-RFLP method.
      Results were described as frequency percentages and chi-square test with
      significance at p < 0.05. RESULTS: The patients with TT genotype had
      significantly lower incidence of postoperative nausea and vomiting during the
      first 2 hours (p < 0.001) and between 2 - 24 hours after surgery as compared to
      other genotypes (p < 0.001). The patients with GG genotypes had significantly
      higher incidence of this complaint (p=0.014). CONCLUSION: Polymorphism of ABCB1
      has an association with responsiveness for ondansetron. There is a role for
      genetics in the management of PONV.

PMID- 26208550
TI  - Prophylactic Nasogastric Decompression for Routine Gastrectomy.
AB  - OBJECTIVE: To determine the necessity of using nasogastric tubes for patients
      with gastrectomy. STUDY DESIGN: A non-randomized controlled trial with two arms.
      PLACE AND DURATION OF STUDY: Sichuan Provincial Peoples' Hospital, China, from
      February 2012 to January 2014. METHODOLOGY: One hundred and twenty one patients
      undergoing gastrectomy were assigned into intubation group and control group
      based on patient's own will. The intubation group was intubated with a
      nasogastric tube before operation and extubated at the earliest evidence of
      passed flatus. Clinical outcomes, such as operation time, bleeding volume, time
      to passage of flatus, postoperative complications, and length of stay were
      recorded and compared between the two groups along with patient characteristics.
      RESULTS: The two groups did not differ in patient characteristics with similar
      distribution of gender, age, diagnosis, tumor location and operation type.
      Nasogastric intubation before surgery was not associated with statistically
      significant difference in total surgery duration, bleeding volume of operation or
      postoperative complications. In addition, patients without nasogastric tubes
      resumed oral diet earlier (52.5 +/- 14.1 vs.18.4 +/- 2.0 hours, p < 0.05) and had
      shorter time to first passage of flatus (43.8 +/- 11.2 vs. 49.0 +/- 13.3 hours,
      p=0.02). CONCLUSION: It is safe to give up nasogastric intubation for patients
      undergoing elective gastrectomy and may even result in a better patient outcome.

PMID- 26208551
TI  - Zuckerkandl Tubercle: An Important Landmark in Thyroid Surgery.
AB  - OBJECTIVE: To find out the frequency of Zuckerkandl Tubercle (ZT) and the
      position of recurrent laryngeal nerve with reference to ZK. STUDY DESIGN: Cross
      sectional observational study. PLACE AND DURATION OF STUDY: Surgical Ward-3,
      Jinnah Postgraduate Medical Centre (JPMC), Karachi, from June 2010 to August
      2011. METHODOLOGY: Patients having goiter, aged between 12 - 60 years were
      admitted through OPD and operated after informed written consent. After
      admission, they underwent surgery. ZT and recurrent laryngeal nerve position i.e.
      whether medial, lateral or posterior to ZT was identified during surgery. Data
      was collected on pre-designed proforma and analysed on SPSS version 15 for
      descriptive statistics. RESULTS: Out of the 84 patients ZT was found in 52
      (61.90%) patients. Nineteen patients had grade-I (less than 0.5 cm), 22 (42.3%)
      had grade-II (0.5 - 1 cm) and 11 (21.1%) had grade-III (more than 1 cm) ZT.
      During surgery, 33 (63.4%) patients had recurrent laryngeal nerve medial to ZT,
      15 (28.8%) patients had lateral and in 4 (7.6%) patients recurrent laryngeal
      nerve was engraved posteriorly. CONCLUSION: Zuckerkandl tubercle was found in
      about 62% cases; recurrent laryngeal nerve was located pre-dominantly medial to
      ZT.

PMID- 26208553
TI  - E-Log System in Monitoring of Residency Program: Trainees' Perspective.
AB  - OBJECTIVE: To record residents' perspective about the utility of newly introduced
      E-Log system at the College of Physicians and Surgeons Pakistan (CPSP). STUDY
      DESIGN: Sequential mixed method design using survey questionnaire and in-depth
      interviews. PLACE AND DURATION OF STUDY: CPSP, Regional Center, Lahore, from
      March to June 2014. METHODOLOGY: Data was collected from registered trainees
      through a web-based survey questionnaire on a scale of 1 to 7 about the utility
      of E-log system. In-depth interviews were conducted with 7 students using non
      probability purposive sampling. The interviews were tape recorded and
      subsequently transcribed. Quantitative data was analyzed using SPSS version 20
      and qualitative data was analyzed using content analysis by identifying themes
      and patterns. RESULTS: Atotal of 4399 responses were received. Motivation was
      4.61 +/- 1.98; 4.33 +/- 2.00 remained acknowledgment of control of one's training
      by the new system. Ease of use got a mean score of 4.56 +/- 2.15. CONCLUSION: The
      overall acceptance of the students regarding E-Log system was high. Scheduling IT
      workshop at the start of training will add to the student satisfaction regarding
      utility of E-Log system.

PMID- 26208552
TI  - Effect of Previous Exposure to HBV on Liver Histology and Treatment Response in
      CHC Patients.
AB  - OBJECTIVE: To analyze the influence of previous exposure to HBV on liver
      histology and treatment outcomes in chronic hepatitis C (CHC) patients. STUDY
      DESIGN: Case control study. PLACE AND DURATION OF STUDY: Rawalian Liver Clinic,
      Department of Medicine, Holy Family Hospital, Rawalpindi, from January 2011 to
      December 2012. METHODOLOGY: Medical records of CHC patients attending the
      Rawalian Liver Clinic were retrospectively analyzed. Virological and treatment
      responses along with histological changes were compared between cases (anti-HBc
      positive) and controls (anti-HBc negative). Significance was determined through
      chi-square test at p < 0.05. RESULTS: Among the 592 CHC patients, 254 (42.9%) had
      serological evidence of a positive anti-HBc (cases) and 338 (57.1%), patients had
      negative anti-HBc (controls). No significant difference was found between ETR,
      SVR and treatment responses (n=220) between the two groups. Out of 65 patients
      whose liver biopsy data was available, cases were more likely to respond in the
      absence of fibrosis [63.2%, (n=24) vs. 36.8%, (n=14), p=0.001]. The controls
      responded more in the presence of fibrosis [100% (n=9) vs. 0, p=0.001]. There was
      no significant effect of anti-HBc positivity on grades of inflammation and
      consequent treatment response (p=0.14). CONCLUSION: There are a significant
      number of CHC patients with markers of previous HBV infection in Pakistani
      population. Previous HBV (anti-HBc positive) does not seem to have an adverse
      effect on liver histology and treatment responses in HBV infection.

PMID- 26208554
TI  - Transient Corneal Edema After Phacoemulsification.
AB  - OBJECTIVE: To determine the association between pre-operative and intra-operative
      factors leading to transient corneal edema after phacoemulsification. STUDY
      DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Department of Ophthalmology,
      Shifa Foundation Community Health Centre, Islamabad, from October 2011 to
      September 2012. METHODOLOGY: Patients undergoing phacoemulsification and
      Intraocular Lens (IOL) implantation were enrolled in the study using consecutive
      non-probability sampling. Pre-operative risk factors including peripheral corneal
      degenerations, the type and density of cataract were documented. Surgical risk
      factors included the incision site, the type of intraocular lens, the
      phacotechnique and the phacopower time. Postoperatively the patients were
      assessed for corneal clarity and the degree of striate keratopathy. Statistical
      analysis was done using SPSS version 17. RESULTS: There were 43% male and 57%
      female patients (n = 182). Mean age was 58.92 +/- 13.00 years (median and mode-60
      years). Factors which increased the risk of transient corneal edema after
      phacoemulsification included hypertension (p = 0.022), dense nuclear cataracts
      (p=0.006), divide and conquer technique (p = 0.008), duration of phacopower use
      (p < 0.001) and peripheral corneal degenerations (p < 0.001). CONCLUSION:
      Patients with peripheral corneal degenerations and dense nuclear cataracts had
      significantly higher rates of postoperative corneal edema. Use of phaco-chop
      technique and less phaco-power time helps in decreasing corneal edema.

PMID- 26208555
TI  - Radiation Dose-rate Reduction Pattern in Well-differentiated Thyroid Cancer
      Treated with I-131.
AB  - OBJECTIVE: To determine the patterns of dose rate reduction in single and
      multiple radioiodine (I-131) therapies in cases of well differentiated thyroid
      cancer patients. STUDY DESIGN: Analytical series. PLACE AND DURATION OF STUDY:
      Department of Nuclear Medicine and Radiation Physics, Multan Institute of Nuclear
      Medicine and Radiotherapy (MINAR), Multan, Pakistan, from December 2006 to
      December 2013. METHODOLOGY: Ninety three patients (167 therapies) with well
      differentiated thyroid cancer treated with different doses of I-131 as an in
      patient were inducted. Fifty four patients were given only single I-131 therapy
      dose ranging from 70 mCi (2590 MBq) to 150 mCi (5550 MBq). Thirty nine patients
      were treated with multiple I-131 radioisotope therapy doses ranging from 80 mCi
      (2960 MBq) to 250 mCi (9250 MBq). T-test was applied on the sample data showed
      statistically significant difference between the two groups with p-value (p <
      0.01) less than 0.05 taken as significant. RESULTS: There were 68 females and 25
      males with an age range of 15 to 80 years. Mean age of the patients were 36
      years. Among the 93 cases of first time Radio Active Iodine (RAI) therapy, 59
      cases (63%) were discharged after 48 hours. Among 39 patients who received RAI
      therapy second time or more, most were discharged earlier after achieving
      acceptable discharge dose rate i.e 25 uSv/hour; 2 out of 39 (5%) were discharged
      after 48 hours. In 58% patients, given single I-131 therapy dose, majority of
      these were discharged after 48 hours without any major complications. CONCLUSION:
      For well differentiated thyroid cancer patients, rapid dose rate reduction is
      seen in patients receiving second or subsequent radioiodine (RAI) therapy, as
      compared to first time receiving RAI therapy.

PMID- 26208556
TI  - Comparison of Opinion Referendum of Medical and Dental Postgraduates Towards
      Plagiarism in Bhopal - Central India.
AB  - OBJECTIVE: To evaluate awareness and attitude towards plagiarism of postgraduates
      of health fraternity in Bhopal, Central India. STUDY DESIGN: Across-sectional
      survey. PLACE AND DURATION OF STUDY: People's University, Bhopal, Madhya Pradesh,
      India, from January to March 2014. METHODOLOGY: A total of 164 postgraduates,
      medical (n = 80) and dental postgraduates (n = 84) were included in the study. A
      standard pre-tested self-administered questionnaire assessing positive, negative
      and subjective norms towards plagiarism was the assessing tool. Data was captured
      through distribution of the instrument and collected as scheduled from the study
      participants. The distribution of scores based on the responses to the individual
      questions in each dimension between the groups were compared using Mann-Whitney U
      test. RESULTS: Among dental and medical postgraduates the median values for the
      questions under positive attitude was 34.0 and 32.0, negative attitude was 21.5
      and 19, subjective norms was 29.0 and 27.5 respectively. The difference in the
      opinion regarding positive attitude was found to be statistically significant in
      between the groups (p < 0.05). CONCLUSION: Overall plagiarism was favored more by
      dental students as compared to medical students. Moreover, inadequate level of
      knowledge and awareness was observed in both the streams. Efforts should be
      undertaken to motivate health professionals to instill honest behavior in order
      to preserve the intellectual property right.

PMID- 26208557
TI  - The Defence of Artificial Life by Synthetic Biology From Ethical and Social
      Aspects.
AB  - Synthetic biology opens up exciting new opportunities for research and industry.
      Although the work of synthetic biologists presents many beneficial applications,
      it also raises potentially serious ethical concerns. Therefore, clear ideas must
      be formed regarding its ethical and social implications, e.g., public perception,
      safety, security, intellectual property rights and so on. In this review, the
      authors identified four issues relevant to synthetic biology and discussed
      associated ethical and practical implications. By weighing these perspectives of
      all sides, this paper clarifies the point that synthetic biology, as an emerging
      discipline with many anticipated benefits and positive impacts on society, can
      acquire moral support and ethical defence. Therefore, synthetic biologists should
      not be shackled with heavy ethical chains, but we must ensure that research is
      conducted under strict control and effective supervisory methods. 

PMID- 26208558
TI  - Sweet's Syndrome: An Evidence-Based Report.
AB  - Sweet's syndrome encompasses a variety of neutrophilic dermatosis characterized
      by acute onset of erythematous, edematous, painful papules, plaques and nodules
      associated with systemic symptoms, peripheral blood leukocytosis and histological
      findings of dense neutrophilic infiltrate. Ten patients were diagnosed during a
      period of one year. The patient population consisted of 7 females and 3 males
      with mean age of 47.6 years ranging from 32 to 60 years. An associated disorder
      was observed in 6 patients which were diabetes, hypothyroidism, hypertension and
      inflammatory bowel disease. Two cases of pregnancy associated disease were
      observed. Cutaneous lesions consisted of erythematous plaques or nodules. Lesions
      were located mainly on the face, neck and upper extremities. All biopsy specimens
      demonstrated a dermal infiltrate composed predominantly of neutrophils. Seven
      patients were treated by oral corticosteroids and three by oral dapsone, all for
      a period of 6 weeks. 

PMID- 26208559
TI  - Competencies Required in a Specialist Doctor in Pakistani Context.

PMID- 26208560
TI  - Orthopaedic Surgeons as Clinical Leaders in the National Health Service, United
      Kingdom (NHS UK): Can the World Learn From Us?
AB  - This article outlines some of the key concepts in leadership (both styles and
      theories) to provide a platform for further learning and to help the modern day
      orthopaedic surgeons to apply these concepts to their current practice. It is
      focused on two major aspects: management of medical organizations and effective
      twenty-first century care by surgeons through proper leadership guide and aimed
      in improving patient care outcomes. Practicing proper leadership skills based on
      evidence resulted in effective management of organization. Thus achieving
      patient's satisfaction. 

PMID- 26208561
TI  - Resection of Posterior Mediastinal Tumors by Video Assisted Thoracic Surgery.
AB  - This case report illustrates successful Video Assisted Thoracic Surgery (VATS)
      performed on a 45-year-old woman and 52-year-old man presenting with a mass in
      left and right paravertebral space on the CT scan respectively. VATS has many
      benefits over traditional open operation (thoracotomy), resulting in less pain
      and shorten recovery time. However, VATS has higher equipment cost but when an
      experienced surgeon performs the surgery, better outcomes are achieved. VATS is
      not common in Pakistan's surgical setup as it is an expensive method of
      eradicating mediastinal pathologies and not every patient undergoes VATS. The
      primary objective of presenting these cases is to promote the use of VATS
      specifically for removal of posterior mediastinal tumors and improve the surgical
      outcomes.

PMID- 26208562
TI  - Idiopathic Spontaneous Intraperitoneal Haemorrhage.
AB  - Idiopathic spontaneous intraperitoneal haemorrhage is a rare and potentially
      fatal condition. Pre-operative diagnosis is difficult or rarely possible. Urgent
      surgical exploration is the treatment of choice. We report a case of spontaneous
      intraperitoneal haemorrhage that was observed undergoing sudden deterioration of
      her condition while in a hospital ward. She was attending to her child admitted
      in the ward. She developed lower abdominal pain and extreme weakness. Hospital
      staff recognized her to be gradually undergoing a state of shock. She was
      resuscitated and urgent ultrasound abdomen revealed free fluid in the abdomen and
      pelvis. Immediate laparotomy confirmed the diagnosis of spontaneous
      intraperitoneal bleeding, however, no significant cause of bleeding was found
      except for a very small area of breached peritoneum in the pouch of Douglas.
      Haemostasis was secured by two stitches of vicryl. Postoperative CT scan of
      abdomen and pelvis did not reveal any abnormal finding. Patient was followed-up
      in the OPD for 6 months and she was symptom-free and in a healthy state.

PMID- 26208563
TI  - Acute Disseminated Encephalomyelitis in a Child Following Plasmodium vivax
      Malaria.
AB  - Acute Disseminated Encephalomyelitis (ADEM) is a multifocal, monophasic, acute
      demyelinating disease of the brain and spinal cord, which is commonly preceded by
      viral infections and occasionally bacterial infections or immunizations. Its
      occurrence following malarial infection, especially Plasmodium vivax Malaria is
      very uncommon. We report an 11-year girl who presented with clinical features of
      encephalopathy and generalized convulsions, 10 days following complete recovery
      from the Plasmodium vivax Malaria. Diagnosis of ADEM as a complication of
      Plasmodium vivax Malaria was made based on acute onset of neurological events,
      characteristic findings on Magnetic Resonance Imaging (MRI) of brain and prompt
      response to corticosteroid therapy. Follow-up MRI, 6 months after discharge,
      showed complete resolution of change found on the initial MRI. To the best of our
      knowledge, only two such cases have been reported in the English literature till
      date.

PMID- 26208564
TI  - Pulmonary Alveolar Proteinosis: A Rare Cause of Respiratory Failure.
AB  - Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome in the paediatric age
      group and characterized by intra-alveolar accumulation of proteinaceous
      phospholipid-laden material called surfactant. The diagnosis is made by High
      Resolution Computed Tomography (HRCT) chest which shows characteristic crazy
      paving appearance and diagnosis confirmed by Bronchoalveolar Lavage (BAL). We
      report two cases. First was a 9-month old infant who presented with respiratory
      distress and peripheral cyanosis since birth. He was diagnosed on High Resolution
      Computed Tomography (HRCT) chest as a case of pulmonary alveolar proteinosis and
      broncho-alveolar lavage confirmed his diagnosis. Second case was a 10-year old
      female child who had a history of repeated chest infections for 5 years and now
      presented with cough and respiratory distress for 45 days. She was also diagnosed
      on HRCT chest but unfortunately she died before bronchoalveolar lavage.

PMID- 26208565
TI  - Trends in Quinolone Resistance Among Common Urinary Tract Isolates Over Three
      Years.
AB  - Quinolones are one of the most frequently prescribed antimicrobials for the
      treatment of urinary tract infections. The aim of the study was to determine the
      rate and pattern of Quinolone resistance among common urinary tract isolates from
      January 2011 to December 2013 in patients with Urinary Tract Infection (UTI). A
      total of 5891 of all clinical isolates were included in the study. The most
      prevalent urinary isolate was Escherichia coli, responsible for 70% UTIs in
      outpatients and 63% in indoor patients. The resistance was 85%, 64% and 62% and
      89%, 76%, and 73% to Nalidixic acid, Norfloxacin and Ciprofloxacin among the out
      patients and for Indoor patients respectively. Resistance was also remarkably
      high among other urinary tract isolates. This high rate of Quinolone resistance
      among all urinary tract isolates makes it a questionable first line empirical
      treatment for UTI.

PMID- 26208566
TI  - Association of Physical Exercise on Anxiety and Depression Amongst Adults.
AB  - This study was done to determine the frequency of anxiety, depression among those
      who exercise regularly and those who do not. Across-sectional study was conducted
      at different gymnasiums of Karachi in July-August 2013. A total 269 individual's
      ages were 18 - 45 years completed a self-administered questionnaire to assess the
      data using simple descriptive statistics. One hundred and thirty four individuals
      were those who did not perform exercise which included females (55.0%) being more
      frequently anxious than male (46.4%). Females (39.9%) were more frequently
      depressed as compared to males (26.4%) less depressed. Chi-square test showed
      association between anxiety levels and exercise was significantly increased in
      non-exercisers compared to regular exercisers found to be significant (p=0.015).
      Individuals who performed regular exercise had a lower frequency of depression
      (28.9%) than non-exercisers (41.8%). Physical exercise was significantly
      associated with lower anxiety and depression frequency amongst the studied adult
      population.

PMID- 26208567
TI  - Severe Gingival Recession: Gingival Veneer a Method of Camouflage.

PMID- 26208568
TI  - Multi-Detector Computed Tomography for Superior Mesenteric Artery Aneurysm.

PMID- 26208569
TI  - Iron Chelation in Patients with Transfusion Dependent Thalassemia: An Insight on
      Response to Deferasirox.

PMID- 26208570
TI  - Aspergillus fumigatus Spinal Abscess in an Immunocompetent Child.

PMID- 26208571
TI  - TGFbeta modulates inflammatory cytokines and growth factors to create
      premetastatic microenvironment and stimulate lung metastasis.
AB  - The formation of tumor-promoting premetastatic microenvironment plays a pivotal
      role on metastatic progression. Understanding how the primary tumor can promote
      the formation of premetastatic microenvironment in the lung will aid discovery of
      a final cure for metastatic breast cancer. The murine 4T1 mammary carcinoma cells
      were injected into the mammary fat pads of the BALB/c mice. Days 0-14 were
      considered the premetastatic phase. Lung tissues were examined using hematoxylin
      eosin staining and transmission electron microscopy. After intravenous injection
      of TGFbeta1 pretreated 4T1 cells, the relative pulmonary vascular permeability
      was quantified, the extravasation, survival, and proliferation of tumor cells in
      premetastatic lungs were evaluated, and the levels of S100A8, S100A9, VEGF, and
      Angpt2 were detected in tumor-bearing mice. The results showed that during the
      premetastatic phase, an inflammatory response and inflammation-induced vascular
      hyperpermeability were established, leading to an abnormal pulmonary
      microenvironment, which facilitated extravasation of circulating tumor cells, and
      subsequent survival and proliferation of metastatic tumor cells in a TGFbeta
      dependent manner. Moreover, the expressions of S100A8, S100A9, VEGF, and Angpt2
      were increased, and an induction of these genes by TGFbeta was further observed
      in premetastatic lungs. Thus, this study demonstrated that TGFbeta promoted the
      creation of premetastatic microenvironment by modulating certain crucial
      inflammatory cytokines and growth factors, and finally enhanced the ability of
      circulating cells to seed the lung. 

PMID- 26208572
TI  - Evidence for the presence of clofazimine and its distribution in the healthy
      mouse brain.
AB  - This is the first report of clofazimine (CFZ) penetration and distribution in
      normal mouse brain. Mice were administered 25 mg/kg CFZ or 100 mg/kg CFZ orally,
      daily for 2 weeks. Animals were sacrificed and blood and brain tissues were
      harvested. Liquid chromatography tandem mass spectrometry showed high
      concentrations of CFZ in homogenized brain, with 100 mg/kg dose having
      significantly higher concentration than 25 mg/kg. Matrix-assisted laser
      desorption/ionization spectrometric imaging of brain sections showed widespread
      tissue distribution of CFZ. Our results show dose dependent localization in
      brain.

PMID- 26208573
TI  - Responsible Reporting: Neuroimaging News in the Age of Responsible Research and
      Innovation.
AB  - Besides offering opportunities in both clinical and non-clinical domains, the
      application of novel neuroimaging technologies raises pressing dilemmas.
      'Responsible Research and Innovation' (RRI) aims to stimulate research and
      innovation activities that take ethical and social considerations into account
      from the outset. We previously identified that Dutch neuroscientists interpret
      "responsible innovation" as educating the public on neuroimaging technologies via
      the popular press. Their aim is to mitigate (neuro)hype, an aim shared with the
      wider emerging RRI community. Here, we present results of a media-analysis
      undertaken to establish whether the body of articles in the Dutch popular press
      presents balanced conversations on neuroimaging research to the public. We found
      that reporting was mostly positive and framed in terms of (healthcare) progress.
      There was rarely a balance between technology opportunities and limitations, and
      even fewer articles addressed societal or ethical aspects of neuroimaging
      research. Furthermore, neuroimaging metaphors seem to favour oversimplification.
      Current reporting is therefore more likely to enable hype than to mitigate it.
      How can neuroscientists, given their self-ascribed social responsibility, address
      this conundrum? We make a case for a collective and shared responsibility among
      neuroscientists, journalists and other stakeholders, including funders, committed
      to responsible reporting on neuroimaging research.

PMID- 26208574
TI  - Contested Technologies and Design for Values: The Case of Shale Gas.
AB  - The introduction of new energy technologies may lead to public resistance and
      contestation. It is often argued that this phenomenon is caused by an inadequate
      inclusion of relevant public values in the design of technology. In this paper we
      examine the applicability of the value sensitive design (VSD) approach. While VSD
      was primarily introduced for incorporating values in technological design, our
      focus in this paper is expanded towards the design of the institutions
      surrounding these technologies, as well as the design of stakeholder
      participation. One important methodological challenge of VSD is to identify the
      relevant values related to new technological developments. In this paper, we
      argue that the public debate can form a rich source from which to retrieve the
      values at stake. To demonstrate this, we have examined the arguments used in the
      public debate regarding the exploration and exploitation of shale gas in the
      Netherlands. We identified two important sets of the underlying values, namely
      substantive and procedural values. This paper concludes with two key findings.
      Firstly, contrary to what is often suggested in the literature, both proponents
      and opponents seem to endorse the same values. Secondly, contestation seems to
      arise in the precise operationalization of these values among the different
      stakeholders. In other words, contestation in the Dutch shale gas debate does not
      arise from inter-value conflict but rather from intra-value conflicts. This multi
      interpretability should be incorporated in VSD processes.

PMID- 26208577
TI  - Multiple Vantage Points Regarding HIV/AIDS.

PMID- 26208575
TI  - [Stress and optimal ageing].
AB  - Stress is a stimulus or incident which has an exogenic or endogenic influence on
      an organism and leads to a biological and/or psychological adaptation from the
      organism by adaptation. Stressors can be differentiated by the temporal impact
      (e.g. acute, chronic or acute on chronic), strength and quality. The consequences
      of stress exposure and adaptation can be measured at the cellular level and as
      (sub) clinical manifestations, where this process can be biologically seen as a
      continuum. Over the course of life there is an accumulation of stress incidents
      resulting in a diminution of the capability for adaptation and repair mechanisms.
      By means of various interventions it is possible to improve the individual
      capability for adaptation but it is not currently definitively possible to
      disentangle alterations due to ageing and the development of diseases. As a
      consequence the term "healthy ageing" should be replaced by the concept of
      "optimal ageing". 

PMID- 26208576
TI  - Psychological vulnerability to daily stressors in old age: Results of short-term
      longitudinal studies.
AB  - A growing numbers of intensive longitudinal studies examine the short-term
      variability of behavior in response to daily stressors. Collectively, these
      studies address the vulnerability for stress-related emotional burden as assessed
      in terms of the intraindividual association between daily stressors and negative
      affect (NA). This article provides a brief overview of the relevant research on
      so-called affective reactivity to daily stressors and focuses on findings on
      development of age-related stressor reactivity across the adult lifespan. Two
      theoretical propositions have been put forward. Firstly, it has been postulated
      that aging should be associated with increased affective reactivity, i.e. it has
      been assumed that the vulnerability in terms of physiological stress reactivity
      increases across the adult life span and, thus, a higher stress-induced emotional
      reactivity should result with increasing age. Secondly, it has been argued that
      due to the continued development of emotional self-regulation skills, there
      should be an age-related decrease in stress reactivity and, hence, an increased
      resilience. Findings on age differences in NA reactivity to daily stressors,
      however, have been inconsistent. A possible explanation for the inconsistent
      findings may lie in the fact that the postulated dynamics of increased
      vulnerability or resilience imply different time-related reactions to stressors.
      In particular, the activation and effectiveness of emotional self-regulation
      strategies increase with increasing time intervals from the stressors. This leads
      to the conclusion that with increasing age the resilience for longer periods of
      stress and accumulated stress should increase. Results from our own research
      support this hypothesis, where older adults reacted to multiple stressors in a
      more adaptive way than younger adults. 

PMID- 26208578
TI  - News From the International Council on Women's Health Issues: Moving Towards
      Sustainability in Combating HIV/AIDS.

PMID- 26208579
TI  - Oncoplastic Breast-Conserving Surgery Reduces Mastectomy and Postoperative Re
      excision Rates.
AB  - BACKGROUND: Oncoplastic breast-conserving surgery (BCS) integrates partial
      mastectomy with plastic surgery techniques to facilitate breast cancer resection
      with clear surgical margins and preservation of breast cosmesis. In 2011,
      oncoplastic BCS was adopted as standard surgical treatment for breast cancer
      patients at Virginia Mason Medical Center, Seattle, WA. METHODS: This single
      institution retrospective review evaluates the mastectomy and postoperative re
      excision rates before and after adoption of oncoplastic BCS. All patients
      undergoing surgical treatment of breast cancer were identified from institutional
      databases for the periods January 2009 through December 2010 [standard surgery
      group (SS)] and January 2013 through September 2014 [oncoplastic surgery group
      (OS)]. RESULTS: A total of 812 patients were evaluated; 425 patients were treated
      in the SS group compared with 387 patients in the OS group. The mastectomy rate
      in the SS group was 34% compared with 15% in the OS group (p < 0.001), and the
      average tumor size for patients undergoing BCS was 12.7 mm in the SS group
      compared with 15.4 mm in the OS group (p = 0.04). Despite the larger average
      tumor size, the postoperative re-excision rate for patients undergoing BCS in the
      SS group was 32% as opposed to 18% in the OS group (p < 0.001). CONCLUSIONS:
      Oncoplastic BCS significantly reduced the rates of mastectomy and postoperative
      re-excision in breast cancer patients while treating larger cancers. This study
      suggests that use of OS techniques can effectively treat larger cancers while
      maximizing breast cosmesis and minimizing the need to resort to mastectomy.

PMID- 26208580
TI  - Reoperation for Complications after Lumpectomy and Mastectomy for Breast Cancer
      from the 2012 National Surgical Quality Improvement Program (ACS-NSQIP).
AB  - BACKGROUND: Hospital readmissions and reoperations are quality indicators of
      patient care. In 2012, the National Surgical Quality Improvement Program (ACS
      NSQIP) began reporting details regarding unplanned reoperations within 30 days of
      initial procedure. The main objective of this study was to identify reoperation
      rates as a result of complications and evaluate complications by type of breast
      surgery. METHODS: Patients who underwent surgery for breast cancer were
      identified from the 2012 ACS-NSQIP Participant User File. Breast procedures were
      categorized as mastectomy or lumpectomy, each with or without immediate breast
      reconstruction (IBR). All reoperations and complication-related reoperations were
      categorized on the basis of procedure and diagnosis codes, and rates were
      compared by breast procedure by Chi square tests. RESULTS: Of 18,500 patients,
      781 (4 %) required an unplanned reoperation within 30 days (single reoperation in
      747, 2+ reoperations in 34). Mean time to first reoperation was 13.4 days and
      varied by procedure. A majority (73 %) of ACS-NSQIP coded unplanned reoperations
      were due to complications. Rates of reoperation due to complication were highest
      in mastectomy with IBR (7 %). Most common complications requiring reoperation
      were bleeding, followed by infection and wound-related problems. CONCLUSIONS:
      Unplanned reoperations after breast cancer surgery are more frequent after
      mastectomy with IBR than other breast operations. Bleeding is the most common
      complication requiring reoperation.

PMID- 26208582
TI  - Proceedings of the RAMI Section of Healthcare Informatics Students Meeting,
      Wednesday 20th May 2015, Setanta House, Dublin.

PMID- 26208581
TI  - Long-Term Psychosocial Functioning in Women with Bilateral Prophylactic
      Mastectomy: Does Preservation of the Nipple-Areolar Complex Make a Difference?
AB  - INTRODUCTION: Nipple-sparing prophylactic mastectomy (PM) is an option for women
      at high-risk for breast cancer, and may offer better cosmetic results than a skin
      sparing PM where the nipple-areolar complex (NAC) is removed. However, there may
      be residual breast cancer risk due to the maintained NAC. It is unclear if
      sparing the NAC with PM impacts on psychosocial functioning, including cancer
      related distress and body image after PM. METHODS: This was a cross-sectional
      survey study of women who had undergone bilateral PM (no previous breast cancer)
      recruited through surgical or cancer genetics clinics. All women completed
      standardized questionnaires assessing cancer-related distress, anxiety,
      depression, satisfaction with decision, decision regret, and health-related
      quality of life related to breast surgery. Outcomes were compared between women
      with nipple-areola-sparing PM (NAC-PM) and skin-sparing PM (SS-PM). RESULTS:
      Overall, 137 women completed the study; 53 (39%) had NAC-PM and 84 (61%) had SS
      PM. The mean age of the study population was 41.5 years [standard deviation (SD)
      8.8] and the mean time between PM and questionnaire completion was 50 months (SD
      31). On the BREAST-Q, we found that women with NAC-PM had significantly higher
      levels of satisfaction with breasts (p = 0.01), satisfaction with outcome (p =
      0.02), and sexual well-being (p < 0.001) compared with SS-PM. No statistically
      significant differences in total cancer-related distress (p = 0.89), anxiety (p =
      0.86), or depression (p = 0.93) were observed between the two groups.
      CONCLUSIONS: Overall, women with NAC-PM had better body image and sexual
      functioning compared with women with SS-PM, while both groups had comparable
      levels of cancer-related distress and perception of breast cancer risk.

PMID- 26208583
TI  - Investigation of cardiovascular disease risk in women with uterine leiomyomas.
AB  - OBJECTIVE: The aim of this study was to investigate the cardiovascular disease
      risk of patients with uterine leiomyoma using carotid intima-media thickness
      (CIMT), insulin resistance and lipid profile. METHODS: A total of 84 reproductive
      aged women (20-45 years) were divided into two groups as the study group (n = 42)
      of women with leiomyoma and the control group (n = 42) of healthy women without
      leiomyoma. The risk factors for cardiovascular disease such as age, body mass
      index (BMI), low-density lipoprotein (LDL), triglycerides (Tg), high-density
      lipoprotein (HDL), total cholesterol and lipoprotein a levels, systemic
      disorders, cigarette smoking and CIMT were all recorded and compared between
      groups. RESULTS: The mean age, gravida, parity, BMI, total cholesterol level and
      CIMT were significantly different between the groups (p < 0.05). CIMT after
      adjusted for the age and age, BMI was significantly lower in study groups
      (<0.001). Insulin resistance, serum LDL, Tg, HDL, lipoprotein a, and endometrial
      thickness were comparable between groups (p > 0.05). The number of leiomyoma was
      significantly correlated with Tg (r = 0. 322, p = 0.037) and LDL (r = 0. 431, p =
      0.006). The size of leiomyoma was significantly correlated with HOMA-IR values (r
      = -0.370, p = 0.016). CONCLUSION: Uterine leiomyoma was associated with lipid
      profile, insulin resistance and CIMT in reproductive-aged women.

PMID- 26208585
TI  - Monoclonal antibodies indicate low-abundance links between heteroxylan and other
      glycans of plant cell walls.
AB  - MAIN CONCLUSION: The derivation of two sensitive monoclonal antibodies directed
      to heteroxylan cell wall polysaccharide preparations has allowed the
      identification of potential inter-linkages between xylan and pectin in potato
      tuber cell walls and also between xylan and arabinogalactan-proteins in oat grain
      cell walls. Plant cell walls are complex composites of structurally distinct
      glycans that are poorly understood in terms of both in muro inter-linkages and
      developmental functions. Monoclonal antibodies (MAbs) are versatile tools that
      can detect cell wall glycans with high sensitivity through the specific
      recognition of oligosaccharide structures. The isolation of two novel MAbs, LM27
      and LM28, directed to heteroxylan, subsequent to immunisation with a potato cell
      wall fraction enriched in rhamnogalacturonan-I (RG-I) oligosaccharides, is
      described. LM27 binds strongly to heteroxylan preparations from grass cell walls
      and LM28 binds to a glucuronosyl-containing epitope widely present in
      heteroxylans. Evidence is presented suggesting that in potato tuber cell walls,
      some glucuronoxylan may be linked to pectic macromolecules. Evidence is also
      presented that suggests in oat spelt xylan both the LM27 and LM28 epitopes are
      linked to arabinogalactan-proteins as tracked by the LM2 arabinogalactan-protein
      epitope. This work extends knowledge of the potential occurrence of inter-glycan
      links within plant cell walls and describes molecular tools for the further
      analysis of such links.

PMID- 26208584
TI  - Tubular atrophy in the pathogenesis of chronic kidney disease progression.
AB  - The longstanding focus in chronic kidney disease (CKD) research has been on the
      glomerulus, which is sensible because this is where glomerular filtration occurs,
      and a large proportion of progressive CKD is associated with significant
      glomerular pathology. However, it has been known for decades that tubular atrophy
      is also a hallmark of CKD and that it is superior to glomerular pathology as a
      predictor of glomerular filtration rate decline in CKD. Nevertheless, there are
      vastly fewer studies that investigate the causes of tubular atrophy, and fewer
      still that identify potential therapeutic targets. The purpose of this review is
      to discuss plausible mechanisms of tubular atrophy, including tubular epithelial
      cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream
      tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal
      transition, interstitial inflammation, lipotoxicity and Na(+)/H(+) exchanger-1
      inactivation. Once a a better understanding of tubular atrophy (and interstitial
      fibrosis) pathophysiology has been obtained, it might then be possible to
      consider tandem glomerular and tubular therapeutic strategies, in a manner
      similar to cancer chemotherapy regimens, which employ multiple drugs to
      simultaneously target different mechanistic pathways. 

PMID- 26208587
TI  - Erratum to: Rats demonstrate helping behavior toward a soaked conspecific.
AB  - Erratum to: Anim CognDOI 10.1007/s10071-015-0872-2. The authors would like to
      correct the word "less" to "more" in the sentence under the heading "Results and
      discussion". The correct sentence should read as: This indicates that the soaked
      rats spent more time in the pool area than did the helper rats.

PMID- 26208586
TI  - Associations of Polymorphisms in mir-196a2, mir-146a and mir-149 with Colorectal
      Cancer Risk: A Meta-Analysis.
AB  - MicroRNAs (miRNAs) are non-coding RNAs which act as tumor suppressors or
      oncogenes. And single nucleotide polymorphism (SNP) in miRNA regions is one type
      of genetic variations in human genome. Various studies have investigated the
      associations of miRNAs SNP and kinds of cancers. In this article, we searched
      eligible studies to explore the relationships between mir-196a2 /mir-146a /mir
      149 polymorphisms and colorectal cancer (CRC). A literature search of PubMed, Web
      of Science and ScienceDirect was conducted to identify all relevant studies.
      Three genetic models with pooled ratio and 95% confidence interval were used to
      evaluate the associations. We found that mir-196a2 polymorphism was significantly
      associated with CRC in Asian group (additive model: OR = 1.197, 95%CI 1.084 ~
      1.32, P < 0.001; dominant model: OR = 1.247, 95%CI 1.065 ~ 1.46, P = 0.006;
      recessive model: OR = 1.298, 95%CI 1.101 ~ 1.531, P = 0.002). And no associations
      were observed between SNPs of mir-146a, mir-149 and CRC in three genetic models.
      We also found CRC risk was not associated with mir-146a and mir-149 polymorphisms
      in population subgroup analysis. The current meta-analysis suggests that mir
      196a2 polymorphism is associated with CRC, especially in Asian group. While, no
      associations have been found between mir-146a /mir-149 polymorphisms and CRC.

PMID- 26208588
TI  - Ergonomic design and evaluation of the handle for an endoscopic dissector.
AB  - The purpose of this study was to design an endoscopic dissector handle and
      objectively assess its usability. The handles were designed with increased
      contact area between the fingers and thumb and the eye rings, and the eye rings
      were modified to have a more perpendicular insertion angle to the finger midline.
      Four different handle models were compared, including a conventional product.
      Subjects performed dissection, exclusion, grasping, precision manipulation and
      precision handling tasks. Electromyography and subjective evaluations were
      measured. Compared to conventional handles, the designated handle reduced the
      muscle load in the extensor and flexor muscles of the forearm and increased
      subjective stability. The activity of the first dorsal interosseous muscle was
      sometimes influenced by the shape of the other parts. The ergonomically designed
      endoscopic dissector handle used in this study achieved high usability. Medical
      instrument designs based on ergonomic concepts should be assessed with objective
      indices. Practitioner Summary: The endoscopic dissector handles were designed
      with increased contact area and more suitable insertion angle between the fingers
      and thumb and the eye rings. Compared to conventional handles, the designated
      handle reduced the muscle load in the extensor and flexor muscles of the forearm
      and increased subjective stability. 

PMID- 26208589
TI  - Subtalar dislocation: management and prognosis for an uncommon orthopaedic
      condition.
AB  - Subtalar dislocations were first described in 1811 as the simultaneous
      dislocation of the talo-calcaneal and talo-navicular joints without any tibio
      talar or talar neck associated fractures. They were classified in 1853 as:
      medial, lateral, posterior and anterior based on the displacement of the foot in
      relationship to the talus. These are uncommon injuries, representing
      approximately 1 % of all traumatic injuries of the foot and 1-2 % of all
      dislocations, being associated with high energy trauma.Closed reduction of these
      dislocations should be performed as early as possible to avoid further damage to
      the skin and neurovascular structures. If this is not possible, then open
      reduction without further delay is recommended. Irreducible injuries have been
      reported in 0 to 47 % of cases. Open dislocations represent between 46 and 83 %
      of all cases, and have been associated with poor prognosis. Associated fractures
      have a high incidence, the most frequent ones are the posterior process of the
      talus, talar head, external malleolus, medial malleolus and the tubercle of the
      fifth metatarsal.These types of injuries are not faced by orthopaedic surgeons on
      a daily basis and having a source of information on how to manage and what to
      expect is important. We present an up-to-date literature review on the
      epidemiology, clinical presentation, radiologic assessment, treatment options and
      prognostic factors of these uncommon injuries.

PMID- 26208590
TI  - A case-control study of breast cancer risk in nurses from Northeastern Ontario,
      Canada.
AB  - PURPOSE: Previously published findings have documented increased breast cancer
      risks associated with the nursing profession. The aim of the present study was to
      assess whether an increased risk of breast cancer was associated with nursing in
      a population-based case-control breast cancer study of women in Northeastern
      Ontario, Canada. METHODS: A total of 1519 women (1380 never-nurses: 716 controls
      and 664 cases; 139 ever-nurses: 59 controls and 80 cases) were included in the
      present study. Study participants filled out a detailed questionnaire which
      included a history of smoking, general health information, breast cancer risk
      factors, and a detailed occupational history. RESULTS: Ever-nurses were at
      higher, but nonsignificant risk of breast cancer compared to never-nurses
      (adjusted OR 1.39, 95 % CI 0.93-2.07). Ever-nurses who worked for longer than 10
      years were at a significantly increased risk of breast cancer compared to never
      nurses (adjusted OR 1.70, 95 % CI 1.04-2.79). A nonsignificant, but increased
      risk of breast cancer was observed in ever-nurses who worked full-time compared
      to never-nurses (OR 1.52, 95 % CI 0.92-2.52), while nurses who worked part-time,
      or both part-time and full-time were not at increased risk. Ever-nurses who
      worked in a hospital setting had a significantly increased risk of breast cancer
      (OR 1.65, 95 % CI 1.04-2.62) compared to never-nurses. CONCLUSIONS: The results
      indicate that the nurses in the present study population are at increased risk of
      breast cancer. A prolonged duration of nursing years and prolonged intensity
      (being a full-time nurse) are factors associated with this increased risk.

PMID- 26208591
TI  - Perspectives of cancer and cancer screening among homeless adults of New York
      City shelter-based clinics: a qualitative approach.
AB  - PURPOSE: Millions of homeless Americans have lower cancer screening and higher
      cancer mortality rates. We explored perspectives and perceptions regarding cancer
      and cancer screening among homeless. METHODS: Using random and criteria sampling,
      we conducted in-depth semi-structured interviews with 50 homeless adults from New
      York City's (NYC) shelters and shelter-based clinics. RESULTS: Mean age was 51.66
      years with average 2.03 years of homelessness; 33/50 were older than 50. Only a
      small number of participants had their recommended cancer screening. Contrary to
      general assumptions and despite significant barriers, the homeless were concerned
      about cancer, believed their risk of cancer is higher compared to the general
      population, and generally considered screening a high priority during
      homelessness. While they acknowledged several individual- and systems-level
      barriers, they welcomed targeted measures to address their multi-level barriers.
      Suggested strategies included active counseling by providers, health education or
      reminders via mHealth strategies or face-to-face in shelters, addressing
      potential providers' prejudice and biases regarding their priorities, incentives,
      and patient navigators or coach to help navigating the complex cancer screening
      process. CONCLUSIONS: There are gaps in effective cancer screening despite
      adequate attitude and perceptions among homeless. The health system needs to
      shift from addressing only basic care to a more equitable approach with
      accessible and acceptable opportunities for preventive cancer care for the
      homeless.

PMID- 26208592
TI  - Dietary inflammatory index and risk of esophageal squamous cell cancer in a case
      control study from Italy.
AB  - PURPOSE: Diet and inflammation have been suggested to be important risk factors
      for esophageal squamous cell cancer (ESCC). In this study, we examined the
      association between the dietary inflammatory index (DII) and ESCC in a case
      control study conducted between 1992 and 1997 in Italy. METHODS: This study
      included 304 ESCC cases and 743 controls hospitalized for acute non-neoplastic
      diseases. The DII was computed based on dietary intake assessed by a reproducible
      and valid 78-item food frequency questionnaire. Logistic regression models were
      used to estimate odds ratios (ORs) conditioned on age, sex, year of interview,
      and area of residence and adjusted for education, smoking, alcohol drinking, BMI,
      physical activity, and aspirin use. Energy adjustment was performed using the
      residual method. RESULTS: Subjects with higher DII scores (i.e., with a more pro
      inflammatory diet) had a higher risk of ESCC, with the DII being used as both a
      continuous variable (ORcontinuous 1.39, 95 % confidence interval, CI, 1.25-1.54;
      one-unit increase corresponding to ~12 % of its range in the current study) and a
      categorical variable (ORquintile5vs1 2.46, 95 % CI 1.40-4.36; p trend < 0.001).
      CONCLUSION: These results indicate that a pro-inflammatory diet is associated
      with a higher risk of ESCC, even after controlling for alcohol and tobacco
      exposure.

PMID- 26208593
TI  - Personalized Orthodontic Accurate Tooth Arrangement System with Complete Teeth
      Model.
AB  - The accuracy, validity and lack of relation information between dental root and
      jaw in tooth arrangement are key problems in tooth arrangement technology. This
      paper aims to describe a newly developed virtual, personalized and accurate tooth
      arrangement system based on complete information about dental root and skull.
      Firstly, a feature constraint database of a 3D teeth model is established.
      Secondly, for computed simulation of tooth movement, the reference planes and
      lines are defined by the anatomical reference points. The matching mathematical
      model of teeth pattern and the principle of the specific pose transformation of
      rigid body are fully utilized. The relation of position between dental root and
      alveolar bone is considered during the design process. Finally, the relative pose
      relationships among various teeth are optimized using the object mover, and a
      personalized therapeutic schedule is formulated. Experimental results show that
      the virtual tooth arrangement system can arrange abnormal teeth very well and is
      sufficiently flexible. The relation of position between root and jaw is
      favorable. This newly developed system is characterized by high-speed processing
      and quantitative evaluation of the amount of 3D movement of an individual tooth. 

PMID- 26208594
TI  - Spleen Segmentation and Assessment in CT Images for Traumatic Abdominal Injuries.
AB  - Spleen segmentation is especially challenging as the majority of solid organs in
      the abdomen region have similar gray level range. Physician analysis of computed
      tomography (CT) images to assess abdominal trauma could be very time consuming
      and hence, automating this process can reduce time to treatment. The proposed
      method presented in this paper is a fully automated and knowledge based technique
      that employs anatomical information to accurately segment the spleen in CT
      images. The spleen detection procedure is proposed to locate the spleen in both
      healthy and injured cases. In the presence of hemorrhage and laceration, the edge
      merging technique is used. The accuracy of the method is measured by some
      criteria such as mis-segmented area, accuracy, specificity and sensitivity. The
      results show that the proposed spleen segmentation method performs well and
      outperforms other methods. 

PMID- 26208595
TI  - Development and User Research of a Smart Bedside Station System toward Patient
      Centered Healthcare System.
AB  - User experience design that reflects real-world application and aims to support
      suitable service solutions has arisen as one of the current issues in the medical
      informatics research domain. The Smart Bedside Station (SBS) is a screen that is
      installed on the bedside for the personal use and provides a variety of
      convenient services for the patients. Recently, bedside terminal systems have
      been increasingly adopted in hospitals due to the rapid growth of advanced
      technology in healthcare at the point of care. We designed user experience (UX)
      research to derive users' unmet needs and major functions that are frequently
      used in the field. To develop the SBS service, a service design methodology, the
      Double Diamond Design Process Model, was undertaken. The problems or directions
      of the complex clinical workflow of the hospital, the requirements of
      stakeholders, and environmental factors were identified through the study. The
      SBS system services provided to patients were linked to the hospital's main
      services or to related electronic medical record (EMR) data. Seven key services
      were derived from the results of the study. The primary services were as follows:
      Bedside Check In and Out, Bedside Room Service, Bedside Scheduler, Ready for
      Rounds, My Medical Chart, Featured Healthcare Content, and Bedside Community.
      This research developed a patient-centered SBS system with improved UX using
      service design methodology applied to complex and technical medical services,
      providing insights to improve the current healthcare system. 

PMID- 26208596
TI  - Do Geographical Locations Affect in Hospitals Performance? A Multi-group Data
      Envelopment Analysis.
AB  - Hospitals are the main and the last component of the health care systems.
      Therefore, evaluating the performance of hospitals is vital. Several studies are
      done in hospitals evaluation, but almost none of them consider the geographical
      features. This paper proposes a new approach for evaluating hospitals. In the
      proposed approach, hospitals are classified into various groups and each group is
      equivalent to a province. It causes hospitals in each category (province) must be
      evaluated in homogenous environment. For this purpose, the conventional data
      envelopment analysis (DEA) model has been developed to this structure. The main
      feature of the proposed model is that it takes into consideration the
      geographical location. In other words, we propose a multi-group DEA model. The
      data on 288 Iranian hospitals grouped under 31 provinces are used to demonstrate
      the model. The results show that the efficiency scores are greatly changed when
      hospitals are evaluated in own groups. 

PMID- 26208598
TI  - Effect of the racket mass and the rate of strokes on kinematics and kinetics in
      the table tennis topspin backhand.
AB  - The purpose of this study was to investigate the effect of the racket mass and
      the rate of strokes on the kinematics and kinetics of the trunk and the racket
      arm in the table tennis topspin backhand. Eight male Division I collegiate table
      tennis players hit topspin backhands against topspin balls projected at 75 balls
      . min(-1) and 35 balls . min(-1) using three rackets varying in mass of 153.5,
      176 and 201.5 g. A motion capture system was used to obtain trunk and racket arm
      motion data. The joint torques of the racket arm were determined using inverse
      dynamics. The racket mass did not significantly affect all the trunk and racket
      arm kinematics and kinetics examined except for the wrist dorsiflexion torque,
      which was significantly larger for the large mass racket than for the small mass
      racket. The racket speed at impact was significantly lower for the high ball
      frequency than for the low ball frequency. This was probably because pelvis and
      upper trunk axial rotations tended to be more restricted for the high ball
      frequency. The result highlights one of the advantages of playing close to the
      table and making the rally speed fast. 

PMID- 26208599
TI  - On the context dependence of emotion displays: Perceptions of gold medalists'
      expressions of pride.
AB  - In spite of various claims for cross-cultural differences in the experience of
      pride, studies on the expression of pride have revealed few cross-cultural
      differences. Five studies using archival data from Olympic and national
      championships do show cross-cultural differences in the expression of pride and
      other positive emotions in pride-eliciting contexts, contingent on the social
      context of the expression, notably the in-group or out-group status of the
      audience. Chinese gold medalists were perceived to express less pride than
      American medalists when outperforming in-group competitors; when outperforming
      out-group members, however, no or smaller cross-cultural differences were
      observed. These findings are important because they indicate that cultural norms
      about emotion expression may be activated only in situations in which they serve
      a function in coordinating people's behaviour.

PMID- 26208597
TI  - Geldanamycin Reduces Abeta-Associated Anxiety and Depression, Concurrent with
      Autophagy Provocation.
AB  - Neurodegenerative disorders are generally characterized by abnormal aggregation
      and deposition of specific proteins. Amyloid beta (Abeta)-associated
      neurodegenerative disorder is characterized by an oxidative damage that, in turn,
      leads to some behavioral changes before the establishment of dementia such as
      depression and anxiety. In the current study, we investigated the effect of heat
      shock protein 90 inhibitor geldanamycin (GA) administration 24 h before Abeta
      injection. In our experiment, 7 days after Abeta injection, elevated plus maze
      and forced swimming test were conducted to assess anxiety and depression-like
      behaviors. Levels of autophagy markers and malondialdehyde (MDA) and also
      activity of catalase in the hippocampus of rats were evaluated. Our behavioral
      analyses demonstrated that GA pretreatment can significantly decrease anxiety-
      and depression-like behaviors in Abeta-injected rats. Also, levels of autophagy
      markers including Atg12, Atg7, and LC3-II increased, while MDA level decreased
      and the activity of catalase increased in rats pretreated with GA compared to
      Abeta-injected rats. Thus, we assumed that GA, at least in part, ameliorated
      Abeta-mediated anxiety and depression by inducing autophagy and improving
      antioxidant defense system.

PMID- 26208600
TI  - Human microtubule affinity-regulating kinase 4 is stable at extremes of pH.
AB  - MAP/microtubule affinity-regulating kinase 4 (MARK4) is a member of adenosine
      monophosphate-activated protein kinases, directly associated with cancer and
      neurodegenerative diseases. Here, we have cloned, expressed, and purified two
      variants of MARK4 [the kinase domain (MARK4-F2), and kinase domain along with 59
      N-terminal residues (MARK4-F1)] and compared their stability at varying pH range.
      Structural and functional changes were observed by incubating both forms of MARK4
      in buffers of different pH. We measured the secondary structure of MARK4 using
      circular dichroism and tertiary structure by measuring intrinsic fluorescence and
      absorbance properties along with the size of proteins by dynamic light
      scattering. We observed that at extremes of pH (below pH 3.5 and above pH 9.0),
      MARK4 is quite stable. However, a remarkable aggregate formation was observed at
      intermediate pH (between pH 3.5 and 9.0). To further validate this result, we
      have modeled both forms of MARK4 and performed molecular dynamics simulation for
      15 ns. The spectroscopic observations are in excellent agreement with the
      findings of molecular dynamics simulation. We also performed ATPase activity at
      varying pH and found a significant correlation of structure of MARK4 with its
      enzyme activity. It is interesting to note that both forms of MARK4 are showing a
      similar pattern of structure changes with reference to pH. 

PMID- 26208602
TI  - HIV-positive African-American women's perspectives on engaging communities in the
      response to HIV/AIDS in Washington, D.C.
AB  - The number of African-American women infected with HIV in Washington, D.C. is
      growing at an alarming rate. However, the perspectives of these women on engaging
      communities in the response to HIV/AIDS have been lacking in the literature. To
      fill this gap, in-depth interviews with 18 HIV-positive African-American women
      living in D.C. were conducted and analyzed using thematic network analysis. Three
      key themes emerged from these interviews: (1) the importance of the church in
      building HIV/AIDS community competence; (2) women's interest in HIV/AIDS
      advocacy; and (3) the negative effects of stigma and limited social bonds on
      community engagement. We conclude by suggesting that more research is needed on
      the role of African-American women in community capacity building, as well as
      greater involvement of churches in HIV/AIDS responses. 

PMID- 26208601
TI  - Domain-Swapping Switch Point in Ste20 Protein Kinase SPAK.
AB  - The related protein kinases SPAK and OSR1 regulate ion homeostasis in part by
      phosphorylating cation cotransporter family members. The structure of the kinase
      domain of OSR1 was determined in the unphosphorylated inactive form and, like
      some other Ste20 kinases, exhibited a domain-swapped activation loop. To further
      probe the role of domain swapping in SPAK and OSR1, we have determined the
      crystal structures of SPAK 63-403 at 3.1 A and SPAK 63-390 T243D at 2.5 A
      resolution. These structures encompass the kinase domain and different portions
      of the C-terminal tail, the longer without and the shorter with an activating
      T243D point mutation. The structure of the T243D protein reveals significant
      conformational differences relative to unphosphorylated SPAK and OSR1 but also
      has some features of an inactive kinase. Both structures are domain-swapped
      dimers. Sequences involved in domain swapping were identified and mutated to
      create a SPAK monomeric mutant with kinase activity, indicating that monomeric
      forms are active. The monomeric mutant is activated by WNK1 but has reduced
      activity toward its substrate NKCC2, suggesting regulatory roles for domain
      swapping. The structure of partially active SPAK T243D is consistent with a
      multistage activation process in which phosphorylation induces a SPAK
      conformation that requires further remodeling to build the active structure. 

PMID- 26208603
TI  - Low birthweight is associated with an increased risk of LADA and type 2 diabetes:
      results from a Swedish case-control study.
AB  - AIMS/HYPOTHESIS: Our aim was to investigate the association between birthweight
      and latent autoimmune diabetes in adults (LADA), a common diabetes form with
      features of both type 1 and type 2 diabetes. METHODS: We used data from the
      Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes (ESTRID), a
      Swedish population-based study. Eligible for the analysis were 134 incident LADA
      cases (glutamic acid decarboxylase antibody [GADA] positive), 350 incident type 2
      diabetes cases (GADA negative) and 603 randomly selected controls. We present ORs
      and 95% CIs for LADA and type 2 diabetes in relation to birthweight, adjusted for
      sex, age, BMI and family history of diabetes. RESULTS: Low birthweight increased
      the risk of LADA as well as the risk of type 2 diabetes; OR per kg reduction was
      estimated as 1.52 (95% CI 1.12, 2.08) and 1.58 (1.23, 2.04), respectively. The OR
      for participants weighing <3 kg compared with >=4 kg at birth was estimated as
      2.38 (1.23, 4.60) for LADA and 2.37 (1.37, 4.10) for type 2 diabetes. A
      combination of low birthweight (<3 kg) and current overweight (BMI >= 25) further
      augmented the risk: LADA, OR 3.26 (1.69, 6.29); and type 2 diabetes, OR 39.93
      (19.27, 82.71). Family history of diabetes had little impact on these estimates.
      CONCLUSIONS/INTERPRETATION: Our results suggest that low birthweight may be a
      risk factor for LADA of the same strength as for type 2 diabetes. These findings
      support LADA, despite its autoimmune component, having an aetiology that includes
      factors related to type 2 diabetes.

PMID- 26208604
TI  - A Potential Role for Acrolein in Neutrophil-Mediated Chronic Inflammation.
AB  - Neutrophils (PMNs) are key mediators of inflammatory processes throughout the
      body. In this study, we investigated the role of acrolein, a highly reactive
      aldehyde that is ubiquitously present in the environment and produced
      endogenously at sites of inflammation, in mediating PMN-mediated degradation of
      collagen facilitating proline-glycine-proline (PGP) production. We treated
      peripheral blood neutrophils with acrolein and analyzed cell supernatants and
      lysates for matrix metalloproteinase-9 (MMP-9) and prolyl endopeptidase (PE),
      assessed their ability to break down collagen and release PGP, and assayed for
      the presence of leukotriene A4 hydrolase (LTA4H) and its ability to degrade PGP.
      Acrolein treatment induced elevated production and functionality of collagen
      degrading enzymes and generation of PGP fragments. Meanwhile, LTA4H levels and
      triaminopeptidase activity declined with increasing concentrations of acrolein
      thereby sparing PGP from enzymatic destruction. These findings suggest that
      acrolein exacerbates the acute inflammatory response mediated by neutrophils and
      sets the stage for chronic pulmonary and systemic inflammation. 

PMID- 26208605
TI  - MicroRNA-26a Promotes Regulatory T cells and Suppresses Autoimmune Diabetes in
      Mice.
AB  - Type-1 diabetes (TID) is an autoimmune disease in which the body's own immune
      cells attack islet beta cells, the cells in the pancreas that produce and release
      the hormone insulin. Mir-26a has been reported to play functions in cellular
      differentiation, cell growth, cell apoptosis, and metastasis. However, the role
      of microRNA-26a (Mir-26a) in autoimmune TID has never been investigated. In our
      current study, we found that pre-Mir-26a (LV-26a)-treated mice had significantly
      longer normoglycemic time and lower frequency of autoreactive IFN-gamma-producing
      CD4(+) cells compared with an empty lentiviral vector (LV-Con)-treated non-obese
      diabetic (NOD) mice. Mir-26a suppresses autoreactive T cells and expands Tregs in
      vivo and in vitro. Furthermore, in our adoptive transfer study, the groups
      receiving whole splenocytes and CD25-depleted splenocytes from LV-Con-treated
      diabetic NOD mice develop diabetes at 3 to 4 weeks of age. In comparison, mice
      injected with undepleted splenocytes obtained from LV-26a-treated reversal NOD
      mice develop diabetes after 6-8 weeks. And depletion of CD25(+) cells in the
      splenocytes of reversed mice abrogates the delay in diabetes onset. In
      conclusion, Mir-26a suppresses autoimmune diabetes in NOD mice in part through
      promoted regulatory T cells (Tregs) expression. 

PMID- 26208606
TI  - Does Exercise Influence Pediatric Bone? A Systematic Review.
AB  - BACKGROUND: Periods of growth are thought to be the best time to increase bone
      mineral content, bone area, and areal bone mineral density (aBMD) through
      increased loading owing to high rates of bone modeling and remodeling. However,
      questions remain regarding whether a benefit of exercise is seen at all bone
      sites, is dependent on pubertal status or sex of the child, or whether other
      factors such as diet modify the response to exercise. QUESTIONS/PURPOSES: We
      asked: (1) Does bone-loading exercise in childhood consistently increase bone
      mineral content, bone area, or aBMD? (2) Do effects of exercise differ depending
      on pubertal status or sex? (3) Does calcium intake modify the bone response to
      exercise? METHODS: A literature search identified 22 unique trials for inclusion
      in this meta-analysis of the effect of exercise on bone changes by bone site,
      pubertal status, and sex. Sample sizes ranged from 16 to 410 subjects 3 to 18
      years old with length of intervention ranging from 3 to 36 months. Fifteen of 22
      trials were randomized (child randomized in nine, classroom/school randomized in
      six) and seven were observational trials. Ten trials were Level 2 and 11 were
      Level 3 based on the Oxford Centre for Evidence-Based Medicine criteria. Random
      effects models tested the difference (intervention mean effect-control mean
      effect) in percent change in bone mineral content, bone area, and aBMD. Meta
      regression was used to identify sources of heterogeneity and funnel plots were
      used to assess publication bias. RESULTS: Children assigned to exercise had
      greater mean percent changes in bone mineral content and aBMD than children
      assigned to the control groups. Mean differences (95% CI) in bone mineral content
      percent change between intervention and control groups at total body (0.8; 95%
      CI, 0.3-1.3; p = 0.003), femoral neck (1.5; 95% CI, 0.5-2.5; p = 0.003), and
      spine (1.7; 95% CI, 0.4-3.1; p = 0.01) were significant with no differences in
      bone area (all p > 0.05). There were greater percent changes in aBMD in
      intervention than control groups at the femoral neck (0.6; 95% CI, 0.2-1.1; p =
      0.006) and spine (1.2; 95% CI, 0.6-1.8; p < 0.001). Benefit of exercise was
      limited to children who were prepubertal (bone mineral content: total body [0.9;
      95% CI, 0.2-1.7; p = 0.01], femoral neck [1.8; 95% CI, 0.0-3.5; p = 0.047], spine
      [3.7; 95% CI, 0.8-6.6; p = 0.01], and aBMD: femoral neck [0.6; 95% CI, -0.1-1.2;
      p = 0.07], spine [1.5; 95% CI, 0.7-2.3; p < 0.001]), with no differences among
      children who were pubertal (all p > 0.05). Changes in aBMD did not differ by sex
      (all p > 0.05), although the number of studies providing male-specific results
      was small (six of 22 eligible studies included boys). There was significant
      heterogeneity in bone mineral content and bone area for which a source could not
      be identified. Heterogeneity in spine aBMD was reduced by including calcium
      intake and intervention length as covariates. Three trials designed to determine
      whether calcium intake modified the bone response to exercise all reported a
      greater effect of exercise on leg bone mineral content in children randomized to
      receive supplemental calcium than those receiving placebo. CONCLUSIONS: Exercise
      interventions during childhood led to 0.6% to 1.7% greater annual increase in
      bone accrual, with effects predominantly among children who were prepubertal. If
      this effect were to persist into adulthood, it would have substantial
      implications for osteoporosis prevention. It is important to identify sources of
      heterogeneity among studies to determine factors that might influence the bone
      response to increased exercise during growth. LEVEL OF EVIDENCE: Level II,
      therapeutic study.

PMID- 26208607
TI  - Otto Aufranc Award: Large Heads Do Not Increase Damage at the Head-neck Taper of
      Metal-on-polyethylene Total Hip Arthroplasties.
AB  - BACKGROUND: Fretting and corrosion at head-neck junctions of total hip
      arthroplasties (THAs) have been associated with adverse local tissue reactions in
      patients with both metal-on-polyethylene (MoP) and metal-on-metal (MoM)
      prostheses. Femoral head size contributes to the severity of fretting and
      corrosion in large-diameter MoM THAs, but its impact on such damage in MoP THAs
      remains unknown. QUESTIONS/PURPOSES: (1) Is femoral head size associated with
      increased fretting or corrosion at the head-neck junction in MoP total hips? (2)
      Is duration of implantation associated with increased fretting or corrosion?
      METHODS: The severity of fretting/corrosion on surfaces of head tapers and stem
      trunnions was visually examined in 154 MoP THAs retrieved as part of 3282
      revision surgeries performed at our institution between January 1, 2007, and
      December 31, 2013. Fretting and corrosion damage were subjectively graded by two
      independent observers on a 1 to 4 scale, and their relations to head size, alloy
      combinations, taper/trunnion design, length of implantation (LOI), and location
      were investigated. Differences in scores never exceeded one grade, and this
      occurred in only 17% of examined implants. With the available implants, the study
      provided 88% power to detect differences of 0.5 in fretting or corrosion scores
      in these analyses. RESULTS: Fretting and corrosion of the tapers and the
      trunnions were not affected by head size (p = 0.247, p = 0.471, p = 0.837, and p
      = 0.868, respectively), although taper/trunnion design affected taper fretting (p
      = 0.005) and corrosion (p = 0.0031) and trunnion fretting (p = 0.0028). Head
      taper fretting (observed in 73% of heads) increased with LOI, but head taper
      corrosion (noted in 93% of heads) was not affected. Trunnion fretting (observed
      in 86% of stems) was more severe in mixed-alloy combinations and with increased
      LOI and was more severe proximally. Trunnion corrosion (noted in 72% of stems)
      was also location-dependent with greater corrosion distally. CONCLUSIONS:
      Fretting and corrosion are regular occurrences in MoP THAs, but neither damage
      type was related to femoral head size. Conversely, taper design, LOI, and alloy
      combination affected the severity of both fretting and corrosion. CLINICAL
      RELEVANCE: Although it has been suggested that trunnion corrosion seen in MoP
      bearings is a function of larger diameter heads, our data suggest that larger
      femoral heads may be used for increased damage at the modular junction of MoP
      THAs.

PMID- 26208609
TI  - Education Compensation, Heroes, or "Apps"? Increasing the Supply of Organs for
      Transplant. A Symposium Introduction and Overview.

PMID- 26208608
TI  - Which Fixation Device is Preferred for Surgical Treatment of Intertrochanteric
      Hip Fractures in the United States? A Survey of Orthopaedic Surgeons.
AB  - BACKGROUND: The best treatment for intertrochanteric hip fractures is
      controversial. The use of cephalomedullary nails has increased, whereas use of
      sliding hip screws has decreased despite the lack of evidence that
      cephalomedullary nails are more effective. As current orthopaedic trainees
      receive less exposure to sliding hip screws, this may continue to perpetuate the
      preferential use of cephalomedullary nails, with important implications for
      resident education, evidence-based best practices, and healthcare cost.
      QUESTIONS/PURPOSES: We asked: (1) What are the current practice patterns in
      surgical treatment of intertrochanteric fractures among orthopaedic surgeons? (2)
      Do surgical practice patterns differ based on surgeon characteristics, practice
      setting, and other factors? (3) What is the rationale behind these surgical
      practice patterns? (4) What postoperative approaches do surgeons use for
      intertrochanteric fractures? METHODS: A web-based survey containing 20 questions
      was distributed to active members of the American Academy of Orthopaedic
      Surgeons. Three thousand seven-hundred eighty-six of 10,321 invited surgeons
      participated in the survey (37%), with a 97% completion rate (3687 of 3784
      responded to all questions in the survey). The survey elicited information
      regarding surgeon demographics, preferred management strategies, and decision
      making rationale for intertrochanteric fractures. RESULTS: Surgeons use
      cephalomedullary nails most frequently for treatment of intertrochanteric hip
      fractures. Sixty-eight percent primarily use cephalomedullary nails, whereas only
      19% primarily use sliding hip screws, and the remaining 13% use cephalomedullary
      nails and sliding hip screws with equal frequency. The cephalomedullary nail was
      the dominant approach regardless of experience level or practice setting.
      Surgeons who practiced in a nonacademic setting (71% versus 58%; p < 0.001), did
      not supervise residents (71% versus 61%; p < 0.001), or treated more than five
      intertrochanteric fractures a month (78% versus 67%; p < 0.001) were more likely
      to use primarily cephalomedullary nails. Of the surgeons who used only
      cephalomedullary nails, ease of surgical technique (58%) was cited as the primary
      reason, whereas surgeons who used only sliding hip screws cite familiarity (44%)
      and improved outcomes (37%) as their primary reasons. Of those who use only short
      cephalomedullary nails, ease of technique (59%) was most frequently cited.
      Postoperatively, 67% allow the patient to bear weight as tolerated. Nearly all
      respondents (99.5%) use postoperative chemical thromboprophylaxis. CONCLUSIONS:
      Despite that either sliding hip screw or cephalomedullary nail fixation are
      associated with equivalent outcomes for most intertrochanteric femur fractures,
      the cephalomedullary nail has emerged as the preferred construct, with the
      majority of surgeons believing that a cephalomedullary nail is easier to use,
      associated with improved outcomes, or is biomechanically superior to a sliding
      hip screw. The difference between what is evidence-based and what is done in
      clinical practice may be attributed to several factors, including financial
      considerations, educational experience, or inability of our current outcomes
      measures to reflect the experiences of surgeons. The educators, researchers, and
      policymakers among us must work harder to better define the roles of sliding hip
      screws and cephalomedullary nails and ensure that the increasing population with
      hip fractures receives high-quality and economically responsible care. LEVEL OF
      EVIDENCE: Level V, therapeutic study.

PMID- 26208610
TI  - Organ Donation in the United States--2014.

PMID- 26208611
TI  - Realistic Compensation Systems.

PMID- 26208612
TI  - Social Media and Organ Donation: The Facebook Effect.

PMID- 26208613
TI  - Medical Repatriation: The Intersection of Mandated Emergency Care, Immigration
      Consequences, and International Obligations.

PMID- 26208614
TI  - Veterans Imprisoned by the Violent Shadows of Military War Time: The Expansion of
      the Insanity Defense to Include Post-Traumatic Stress Disorder.

PMID- 26208615
TI  - Differences between automatically detected and steady-state fractional flow
      reserve.
AB  - BACKGROUND: Measurement of fractional flow reserve (FFR) has become a standard
      diagnostic tool in the catheterization laboratory. FFR evaluation studies were
      based on pressure recordings during steady-state maximum hyperemia. Commercially
      available computer systems detect the lowest Pd/Pa ratio automatically, which
      might not always be measured during steady-state hyperemia. We sought to compare
      the automatically detected FFR and true steady-state FFR. METHODS AND RESULTS:
      Pressure measurement traces of 105 coronary lesions from 77 patients with
      intermediate coronary lesions or multivessel disease were reviewed. In all
      patients, hyperemia had been achieved by intravenous adenosine administration
      using a dosage of 140 ug/kg/min. In 42 lesions (40%) automatically detected FFR
      was lower than true steady-state FFR. Mean bias was 0.009 (standard deviation
      0.015, limits of agreement -0.02, 0.037). In 4 lesions (3.8%) both methods lead
      to different treatment recommendations, in all 4 cases instantaneous wave-free
      ratio confirmed steady-state FFR. CONCLUSIONS: Automatically detected FFR was
      slightly lower than steady-state FFR in more than one-third of cases.
      Consequently, interpretation of automatically detected FFR values closely below
      the cutoff value requires special attention.

PMID- 26208616
TI  - An Experimental and Computational Investigation of Bone Formation in Mechanically
      Loaded Trabecular Bone Explants.
AB  - Understanding how bone marrow multipotent stromal cells (MSCs) contribute to new
      bone formation and remodeling in vivo is of principal importance for informing
      the development of effective bone tissue engineering strategies in vitro.
      However, the precise in situ stimuli that MSCs experience have not been fully
      established. The shear stress generated within the bone marrow of physiologically
      loaded samples has never been determined, but could be playing an important role
      in the generation of sufficient stimulus for MSCs to undergo osteogenic
      differentiation. In this study fluid structure interaction (FSI) computational
      models were used in conjunction with a bioreactor which physiologically
      compresses explanted trabecular bone samples to determine whether MSCs can be
      directly stimulated by mechanical cues within the bone marrow. Experimentally
      loaded samples were found to have greater osteogenic activity, as verified by
      bone histomorphometry, compared to control static samples. FSI models
      demonstrated a linear relationship between increasing shear stress and decreasing
      bone volume. The FSI models demonstrated that bone strain, not marrow shear
      stress, was likely the overall driving mechanical signal for new bone formation
      during compression. However, the shear stress generated in the models is within
      the range of values which has been shown previously to generate an osteogenic
      response in MSCs. 

PMID- 26208617
TI  - Age Effects on Upper Limb Kinematics Assessed by the REAplan Robot in Healthy
      Subjects Aged 3 to 93 Years.
AB  - Kinematics is recommended for the quantitative assessment of upper limb
      movements. The aims of this study were to determine the age effects on upper limb
      kinematics and establish normative values in healthy subjects. Three hundred and
      seventy healthy subjects, aged 3-93 years, participated in the study. They
      performed two unidirectional and two geometrical tasks ten consecutive times with
      the REAplan, a distal effector robotic device that allows upper limb
      displacements in the horizontal plane. Twenty-six kinematic indices were computed
      for the four tasks. For the four tasks, nineteen of the computed kinematic
      indices showed an age effect. Seventeen indices (the accuracy, speed and
      smoothness indices and the reproducibility of the accuracy, speed and smoothness)
      improved in young subjects aged 3-30 years, showed stabilization in adults aged
      30-60 years and declined in elderly subjects aged 60-93 years. Additionally, for
      both geometrical tasks, the speed index exhibited a decrease throughout life.
      Finally, a principal component analysis provided the relations between the
      kinematic indices, tasks and subjects' age. This study is the first to assess age
      effects on upper limb kinematics and establish normative values in subjects aged
      3-93 years.

PMID- 26208619
TI  - Is there any point in making co-crystals?
AB  - Many aspects of co-crystals, including their synthesis, characterization and
      possible applications, are receiving considerable attention from academia and
      industry alike. The question is, can this interdisciplinary activity be
      translated into new fundamental insight and new solid forms of high-value
      materials with improved performances. 

PMID- 26208618
TI  - Bariatric and Metabolic Surgery in Adolescents: a Path to Decrease Adult
      Cardiovascular Mortality.
AB  - Obesity is a major health problem across all age groups and has escalated to
      pandemic proportions. The proportion of children with overweight or obesity has
      risen rapidly over recent decades, and it is recognized that most obese children
      become obese adults. Furthermore, BMI is the strongest CV risk factor to track
      from childhood into adulthood. As well as BMI, multiple CV risk factors begin in
      childhood and strong associations between these factors and BMI are evident.
      Clear evidence exists for the CV benefits of reversing obesity in adults, much of
      which examines the effects of bariatric surgery. The capacity of bariatric
      surgery to reliably achieve safe and lasting improvement in BMI is unparalleled,
      and the emerging evidence base in adolescent bariatric surgery has so far
      concurred. In the absence of effective alternatives, it appears that the increase
      in use of bariatric surgery in adolescents will continue.

PMID- 26208620
TI  - Charge density and optical properties of multicomponent crystals containing
      active pharmaceutical ingredients or their analogues.
AB  - Active pharmaceutical ingredients (APIs), through their favourable donor/acceptor
      spatial distribution and synthon formation flexibility, are attractive building
      blocks in modern materials crystallography. The optical properties of a crystal
      strongly depend on two factors, i.e. the spatial distribution of molecules in the
      crystal structure and the electronic properties of molecular building blocks
      (dipole moments, polarizabilities, hyperpolarizabilities). Although the latter
      are easy to predict through ab initio calculations, the former are not. Only a
      combination of experimental and theoretical charge density studies together with
      prediction and measurement of optical properties enable full analysis of the
      obtained functional material in terms of its usefulness in practical
      applications. This article presents design strategies of optical materials based
      on selected pharmaceutical molecules. Factors that contribute to molecular
      recognition in the four selected polar/chiral crystal phases (derived through
      charge density and Hirshfeld surfaces analysis) have been determined.
      Theoretically predicted optical properties of the molecular/ionic building blocks
      as well as bulk effects have been confirmed experimentally. This research is a
      first step in the design of novel optical materials based on push-pull molecules
      and APIs. 

PMID- 26208621
TI  - Structural and energy insights on solid-state complexes with trimethoprim: a
      combined theoretical and experimental investigation.
AB  - We present here a new structure of a 1:1 salt of trimethoprim with hemifumarate,
      highlighted by single-crystal X-ray diffraction and computational conformational
      studies. This salt was formed during cocrystallization assays conducted to
      combine trimethoprim and other APIs whose combination exhibits interesting
      properties. Theoretical in vacuo investigations have been performed on the
      organic salt through a DFT two-dimensional conformational scan of torsion angles
      between the two aromatic moieties of trimethoprim. The evaluation of relative
      energies for hydrogen-bond interactions in the structure has also been performed.
      Comparison with conformational data from structures implying trimethoprim
      retrieved from the Cambridge Structural Database (CSD) shows good agreement with
      theoretical results, proving the validity of vacuum ab initio calculations in
      describing the energetic landscape of the molecule and thereby gain initial
      insight into the prediction process for possible new conformations and therefore
      potential new polymorphs. 

PMID- 26208622
TI  - Non-centrosymmetric crystals of new N-benzylideneaniline derivatives as potential
      materials for non-linear optics.
AB  - Three new N-benzylideneaniline derivatives [p-nitrobenzylidene-p
      phenylamineaniline (I), 2,4-dinitrobenzylidene-p-phenylamineaniline (II) and p
      dinitrobenzylidene-p-diethylamineaniline (III)] containing electron-push-pull
      groups have been prepared. They present a planar N-benzylideneaniline core and
      neighbouring functional atoms, which are related through an efficient
      intramolecular charge transfer (CT). Two of the derivatives crystallize in non
      centrosymmetric space groups, a necessary condition for non-linear optical (NLO)
      responses. The NLO properties were calculated for the molecular conformations
      determined by single-crystal X-ray diffraction as well as for the four molecules
      packed into each corresponding unit cell, using a quantum-chemical method at the
      cam-B3LYP/NLO-V level of theory. As expected from antiparallel face-to-face
      stacking through centrosymmetry, the main NLO descriptors - namely, the first
      hyperpolarizability (betatot) and its projection on the dipole moment direction
      (betavec) - are almost zero for the tetramer of derivative III. Interestingly,
      the calculated first hyperpolarizability decreases in the non-centrosymmetric
      unit-cell content of derivative II when compared to its single molecule, which
      may be related to its molecular pillaring, similar to that observed in derivative
      III. On the other hand, a desirable magnification of the NLO properties was found
      for packed units of derivative I, which may be a consequence of its parallel face
      to-tail stacking with the CT vectors of all molecules pointing in the same
      direction. Moreover, the CT vector of compound I makes an angle of theta = 33.6
      degrees  with its crystal polar axis, resulting in a higher-order parameter
      (cos(3)theta = 0.6) compared with the other derivatives. This is in line with the
      higher macroscopic second-order NLO response predicted for derivative I, betatot
      = 120.4 * 10(-30) e.s.u. 

PMID- 26208623
TI  - Intermolecular interactions of proton transfer compounds: synthesis, crystal
      structure and Hirshfeld surface analysis.
AB  - Three new proton transfer compounds, [2-ammonio-5-methylcarboxybenzene
      perchlorate (1), (C8H10NO2(+).ClO4(-)), 4-(ammoniomethyl)carboxybenzene nitrate
      (2), (C8H10NO2(+).NO3(-)), and 4-(ammoniomethyl)carboxybenzene perchlorate (3),
      (C8H10NO2(+).ClO4(-))], have been synthesized, their IR modes of vibrations have
      been assigned and their crystal structures studied by means of single-crystal X
      ray diffraction. Their asymmetric units consist of one cation and one anion for
      both compounds (1) and (2). However, the crystal structure of compound (3) is
      based on a pair of cations and a pair of anions in its asymmetric unit. The three
      dimensional Hirshfeld surface analysis and the two-dimensional fingerprint maps
      revealed that the three structures are dominated by H...O/O...H and H...H
      contacts. The strongest hydrogen-bonding interactions are associated with O-H...O
      and N-H...O constituting the highest fraction of approximately 50%, followed by
      those of the H...H type contributing 20%. Other close contacts are also present,
      including weak C...H/H...C contacts (with about 10%). 

PMID- 26208624
TI  - From a binary salt to salt co-crystals of antibacterial agent lomefloxacin with
      improved solubility and bioavailability.
AB  - The cocrystallization of lomefloxacin (Lf) with barbituric acid (HBA) and/or
      isophthalic acid (H2ip) leads to novel binary and ternary salts via hydrogen
      bonding recognition. X-ray single-crystal diffraction analyses show that
      zwitterionic lomefloxacin can adjust itself to fulfill a different supramolecular
      array in either binary salts or ternary salt co-crystals, formulated as
      [HLf].[Hip].H2O (1), [HLf].[BA].[HBA].H2O (2) and [HLf].[BA].[H2ip].CH3OH.H2O
      (3). These pharmaceutical agents present uniform charge-assisted hydrogen-bonding
      networks between HLf cations and acidic coformers with the lattice capturing
      water molecules. Structural comparison of (2) and (3) indicated that a delicate
      balance of geometries and hydrogen-bonding partners is required for stacking to
      favor the formation of ternary salt co-crystals. Cocrystallization was able to
      overcome the water insolubility of lomefloxacin. Both the salt co-crystals
      display enhanced solubility and better pharmaceutical applicability. 

PMID- 26208625
TI  - How does binding of imidazole-based inhibitors to heme oxygenase-1 influence
      their conformation? Insights combining crystal structures and molecular
      modelling.
AB  - Heme oxygenase-1 (HO-1) inhibition is associated with antitumor activity.
      Imidazole-based analogues show effective and selective inhibitory potency of HO
      1. In this work, five single-crystal structures of four imidazole-based compounds
      are presented, with an in-depth structural analysis. In order to study the
      influence of the conformation of the ligands on binding to protein,
      conformational data from crystallography are compared with quantum mechanics
      analysis and molecular docking studies. Molecular docking of imidazole-based
      analogues in the active site of HO-1 is in good agreement with the experimental
      structures. Inhibitors interact with the heme cofactor and a hydrophobic pocket
      (Met34, Phe37, Val50, Leu147 and Phe214) in the HO-1 binding site. An alternate
      binding mode can be hypothesized for some inhibitors in the series. 

PMID- 26208626
TI  - Anomalous X-ray diffraction study of Pr-substituted BaCeO3 - delta.
AB  - The effect of Pr doping on the crystal structure and site occupancy was studied
      for the nominally synthesized BaCe1 - xPrxO3 - delta (x = 0, 0.2, 0.4, 0.6 and
      0.8) perovskites using anomalous X-ray powder diffraction (AXRD) data and
      Rietveld analysis. Crystal structure parameters were accurately determined using
      10,000 eV photons, and the Pr occupancy was refined using data collected with
      5962 eV photons, close to the Pr LIII absorption edge. BaCe1 - xPrxO3 - delta
      crystallizes in the Pnma (No. 62) space group for all x values. Pr cations are
      mainly located at the Ce sites (perovskites B site), but a small fraction of them
      increasingly substitute some of the Ba ions at the A site as Pr content
      increases. The Pr doping introduces electronic defects (Pr(+3)/Pr(+4)) and oxygen
      vacancies needed for H2O incorporation and H-ionic conductivity. A decrease in
      the orthorhombic distortion would produce the opposite effects on the electronic
      and ionic mobility. The electronic mobility should increase due to an improvement
      in the overlap of the (Ce/Pr)4f-O2p orbital, while the proton mobility should
      decrease as a consequence of a larger hopping distance.

PMID- 26208627
TI  - A novel characterization of organic molecular crystal structures for the purpose
      of crystal engineering.
AB  - A novel analytical approach is proposed for the characterization of organic
      molecular crystal structures where close packing is an important factor. It
      requires the identification of a unique reference axis within the crystal, along
      which three-dimensional space is divided into close-packed blocks (CPB) and
      junction zones (JZ). The degree of close packing along the reference axis is
      quantified by a two-dimensional packing function, phi2D, of symmetry determined
      by the space group. Values of phi2D reflect the degree of area-filling in planes
      perpendicular to this axis. The requirement of close packing within CPB allows
      the planar structures perpendicular to the reference axis to be analysed as
      tessellations of area-filling molecular-based cells (MBC), which are generally
      hexagonal. The form of these cells reflects the molecular shape in the cross
      section, since their vertices are given by the centres of the voids between
      molecules. There are two basic types of MBC, Type 1, of glide or pseudo-glide
      symmetry, and Type 2, which is formed by lattice translations alone and generally
      requires a short unit-cell axis. MBC at layers of special symmetry are used to
      characterize the structures in terms of equivalent ellipses with parameters aell,
      bell and chiell. The ratio aell/bell allows the established alpha, beta, gamma
      classification to be integrated into the current framework. The values of
      parameters aell and bell arising from all the structures considered, polynuclear
      aromatic hydrocarbons (PAH), substituted anthracenes and anthraquinones (SAA) and
      2-benzyl-5-benzylidene (BBCP) are mapped onto a universal curve. The division of
      three-dimensional space into CPB and JZ is fundamentally useful for crystal
      engineering, since the structural perturbations brought about by substitution at
      hydrogen positions located within JZ are minimal. A contribution is also made to
      ongoing debate concerning the adoption of polar space groups, isomorphism and
      polymorphism. 

PMID- 26208628
TI  - Crystal structure and phase transition in (NH4)3WO2F5: from dynamic to static
      orientational disorder.
AB  - Single crystals of tungsten double salt (NH4)3WO2F5 = (NH4)3[WO2F4]F have been
      synthesized by solid-state reaction or from fluoride solution and its crystal
      structures at 296 and 193 K were determined by X-ray diffraction. At room
      temperature, the crystal structure of the compound is dynamically disordered with
      the ligand atoms statistically distributed on two positions (6e and 24m) of the
      Pm3m unit cell [a = 6.0298 (1) A], and the tungsten atom dynamically disordered
      on 12 orientations forming a spatial cuboctahedron [W12] that enables the real
      geometry of cis-WO2F4 octahedron to be determined with two short W-O distances.
      On cooling, the compound undergoes a first-order phase transition with the
      symmetry change Pm3m -> Pa3 and a doubling of the unit-cell parameter [a =
      11.9635 (7) A]. The ligand F(O) atoms statistically occupy two general 24d sites
      and form W1X6 and W2X6 octahedra, in which the O and F atoms are not
      crystallographically different that means a static orientational disorder of
      (NH4)3WO2F5. 

PMID- 26208629
TI  - An alternative empirical model for the relationship between the bond valence and
      the thermal expansion rate of chemical bonds.
AB  - The relationship between the bond valence s and the thermal expansion rate of
      chemical bonds (dr/dT) has been closely approximated by using the alternative
      three-parameter empirical model (dr/dT) = (u + vs)(-1/w), where u, v and w are
      the refinable parameters. Unlike the s-(dr/dT) model developed by Brown et al.
      [(1997), Acta Cryst. B53, 750-761], this alternative model can be optimized for
      particular s-(dr/dT) datasets in the least-squares refinement procedure. For
      routine calculations of the thermal expansion rates of chemical bonds, the
      alternative model with the parameters u = -63.9, v = 2581.0 and w = 0.647 can be
      recommended. 

PMID- 26208630
TI  - Paediatric HIV treatment failure: a silent epidemic.
AB  - Paediatric antiretroviral treatment (ART) failure is an under-recognized issue
      that receives inadequate attention in the field of paediatrics and within HIV
      treatment programmes. With paediatric ART failure rates ranging from 19.3% to
      over 32% in resource limited settings, a comprehensive evaluation of the causes
      of failure along with approaches to address barriers to treatment adherence are
      urgently needed. In partnership with the local Department of Health, a pilot
      programme has been established by Medecins Sans Frontieres (MSF) in Khayelitsha,
      South Africa, to identify and support paediatric HIV patients with high viral
      loads and potential treatment failure. Through detailed clinical and psychosocial
      evaluations and adherence support with an innovative counselling model, treatment
      barriers are identified and addressed. Demographic and clinical characteristics
      from the cohort show a delayed median start date for ART, prolonged viraemia
      including a large number of patients who have never achieved viral load (VL)
      suppression, a low rate of regimen changes despite failure, and a high percentage
      of pre-adolescent and adolescent patients who have not gone through the
      disclosure process. Stemming this epidemic of paediatric treatment failure
      requires programmatic responses to high viral loads in children, starting with
      improved "case finding" of previously undiagnosed HIV-infected children and
      adolescents. Viral load testing needs to be prioritized over CD4 count
      monitoring, and flagging systems to identify high VL results should be developed
      in clinics. Clinicians must understand that successful treatment begins with good
      adherence, and that simple adherence support strategies can often dramatically
      improve adherence. Moreover, appropriate adherence counselling should begin not
      when the child fails to respond to treatment. Establishing good adherence from
      the beginning of treatment, and supporting ongoing adherence during the
      milestones in these children's lives is key to sustaining treatment success in
      this vulnerable HIV-infected patient population. 

PMID- 26208631
TI  - Investigating the effectiveness of working memory training in the context of
      Personality Systems Interaction theory.
AB  - Previous research has shown mixed results for the ability of working memory
      training to improve fluid intelligence. The aims of this study were first to
      replicate these improvements, and then to explore the moderating role of
      Personality Systems Interaction (PSI) personality factors. By using three
      different training methods and an active-contact control group, we examined the
      effects of 25 days of cognitive training on 142 participants. After examining our
      results in context of PSI theory, we found that different training methods
      yielded different IQ gains in participants, depending on their personality
      styles. In addition, these correlations suggested a meaningful pattern,
      indicating that PSI theory may be able to account for the different outcomes of
      cognitive training studies. Our findings may facilitate tailor-made cognitive
      training interventions in the future, and can contribute to explaining the
      mechanisms underlying the far transfer of working memory training to fluid
      intelligence. 

PMID- 26208632
TI  - Differences in cognitive ability and apparent sex differences in corpus callosum
      size.
AB  - Gender differences in brain structure and function have long been an interest to
      neuroscientists. One region where these differences have been reported is in the
      band of white matter that connects the two cerebral hemisphere, the corpus
      callosum. The current study explores the possibility that differences in
      cognitive ability contribute to the observed gender effects. The focus here is on
      visuo-spatial processing as measured by mental rotation which has also been found
      to have significant gender differences. The results reported show that two
      segments of the corpus callosum revealed gender differences, the rostrum and the
      anterior midbody. Both segments connect cortical regions that have been
      implicated in mental rotation. Additionally, the gender effect found in the
      rostrum appears to be due to visuo-spatial processing while the anterior midbody
      appears to be affected by both visuo-spatial processing and gender. These results
      suggest that because neural structure and cognition are intimately intertwined,
      cognition should be accounted for when making group comparisons of neural
      structure. 

PMID- 26208633
TI  - The pro-inflammatory cytokine 14-3-3epsilon is a ligand of CD13 in cartilage.
AB  - Osteoarthritis is a whole-joint disease characterized by the progressive
      destruction of articular cartilage involving abnormal communication between
      subchondral bone and cartilage. Our team previously identified 14-3-3epsilon
      protein as a subchondral bone soluble mediator altering cartilage homeostasis.
      The aim of this study was to investigate the involvement of CD13 (also known as
      aminopeptidase N, APN) in the chondrocyte response to 14-3-3epsilon. After
      identifying CD13 in chondrocytes, we knocked down CD13 with small interfering RNA
      (siRNA) and blocking antibodies in articular chondrocytes. 14-3-3epsilon-induced
      MMP-3 and MMP-13 was significantly reduced with CD13 knockdown, which suggests
      that it has a crucial role in 14-3-3epsilon signal transduction. Aminopeptidase N
      activity was identified in chondrocytes, but the activity was unchanged after
      stimulation with 14-3-3epsilon. Direct interaction between CD13 and 14-3-3epsilon
      was then demonstrated by surface plasmon resonance. Using labeled 14-3-3epsilon,
      we also found that 14-3-3epsilon binds to the surface of chondrocytes in a manner
      that is dependent on CD13. Taken together, these results suggest that 14-3
      3epsilon might directly bind to CD13, which transmits its signal in chondrocytes
      to induce a catabolic phenotype similar to that observed in osteoarthritis. The
      14-3-3epsilon-CD13 interaction could be a new therapeutic target in
      osteoarthritis. 

PMID- 26208634
TI  - STX13 regulates cargo delivery from recycling endosomes during melanosome
      biogenesis.
AB  - Melanosomes are a class of lysosome-related organelles produced by melanocytes.
      Biogenesis of melanosomes requires the transport of melanin-synthesizing enzymes
      from tubular recycling endosomes to maturing melanosomes. The SNARE proteins
      involved in these transport or fusion steps have been poorly studied. We found
      that depletion of syntaxin 13 (STX13, also known as STX12), a recycling endosomal
      Qa-SNARE, inhibits pigment granule maturation in melanocytes by rerouting the
      melanosomal proteins such as TYR and TYRP1 to lysosomes. Furthermore, live-cell
      imaging and electron microscopy studies showed that STX13 co-distributed with
      melanosomal cargo in the tubular-vesicular endosomes that are closely associated
      with the maturing melanosomes. STX family proteins contain an N-terminal
      regulatory domain, and deletion of this domain in STX13 increases both the SNARE
      activity in vivo and melanosome cargo transport and pigmentation, suggesting that
      STX13 acts as a fusion SNARE in melanosomal trafficking pathways. In addition,
      STX13-dependent cargo transport requires the melanosomal R-SNARE VAMP7, and its
      silencing blocks the melanosome maturation, reflecting a defect in endosome
      melanosome fusion. Moreover, we show mutual dependency between STX13 and VAMP7 in
      regulating their localization for efficient cargo delivery to melanosomes. 

PMID- 26208635
TI  - The Drosophila retinoblastoma protein, Rbf1, induces a Debcl- and Drp1-dependent
      mitochondrial apoptosis.
AB  - In accordance with its tumor suppressor role, the retinoblastoma protein pRb can
      ensure pro-apoptotic functions. Rbf1, the Drosophila homolog of Rb, also displays
      a pro-apoptotic activity in proliferative cells. We have previously shown that
      the Rbf1 pro-apoptotic activity depends on its ability to decrease the level of
      anti-apoptotic proteins such as the Bcl-2 family protein Buffy. Buffy often acts
      in an opposite manner to Debcl, the other Drosophila Bcl-2-family protein. Both
      proteins can localize at the mitochondrion, but the way they control apoptosis
      still remains unclear. Here, we demonstrate that Debcl and the pro-fission gene
      Drp1 are necessary downstream of Buffy to trigger a mitochondrial fragmentation
      during Rbf1-induced apoptosis. Interestingly, Rbf1-induced apoptosis leads to a
      Debcl- and Drp1-dependent reactive oxygen species production, which in turn
      activates the Jun Kinase pathway to trigger cell death. Moreover, we show that
      Debcl and Drp1 can interact and that Buffy inhibits this interaction. Notably,
      Debcl modulates Drp1 mitochondrial localization during apoptosis. These results
      provide a mechanism by which Drosophila Bcl-2 family proteins can control
      apoptosis, and shed light on a link between Rbf1 and mitochondrial dynamics in
      vivo. 

PMID- 26208636
TI  - The homeobox gene DLX4 regulates erythro-megakaryocytic differentiation by
      stimulating IL-1beta and NF-kappaB signaling.
AB  - Megakaryocyte and erythroid development are tightly controlled by a repertoire of
      cytokines, but it is not clear how cytokine-activated signaling pathways are
      controlled during development of these two lineages. Here, we identify that
      expression of DLX4, a transcription factor encoded by a homeobox gene, increases
      during megakaryopoiesis but decreases during erythropoiesis. Enforced expression
      of DLX4 in CD34(+) stem and progenitor cells and in bipotent K562 cells induced
      lineage markers and morphologic features of megakaryocytes and repressed
      erythroid marker expression and hemoglobin levels. Converse results were obtained
      when DLX4 was knocked down. Gene Ontology and Gene Set Enrichment Analyses of
      genome-wide changes in gene expression revealed that DLX4 induces a
      megakaryocytic transcriptional program and inhibits an erythroid transcriptional
      program. DLX4 also induced gene signatures that are associated with nuclear
      factor kappaB (NF-kappaB) signaling. The ability of DLX4 to promote megakaryocyte
      development at the expense of erythroid generation was diminished by blocking NF
      kappaB activity or by repressing IL1B, a transcriptional target of DLX4.
      Collectively, our findings indicate that DLX4 exerts opposing effects on the
      megakaryocytic and erythroid lineages in part by inducing IL-1beta and NF-kappaB
      signaling. 

PMID- 26208637
TI  - Dictyostelium Nramp1, which is structurally and functionally similar to mammalian
      DMT1 transporter, mediates phagosomal iron efflux.
AB  - The Nramp (Slc11) protein family is widespread in bacteria and eukaryotes, and
      mediates transport of divalent metals across cellular membranes. The social
      amoeba Dictyostelium discoideum has two Nramp proteins. Nramp1, like its
      mammalian ortholog (SLC11A1), is recruited to phagosomal and macropinosomal
      membranes, and confers resistance to pathogenic bacteria. Nramp2 is located
      exclusively in the contractile vacuole membrane and controls, synergistically
      with Nramp1, iron homeostasis. It has long been debated whether mammalian Nramp1
      mediates iron import or export from phagosomes. By selectively loading the iron
      chelating fluorochrome calcein in macropinosomes, we show that Dictyostelium
      Nramp1 mediates iron efflux from macropinosomes in vivo. To gain insight in ion
      selectivity and the transport mechanism, the proteins were expressed in Xenopus
      oocytes. Using a novel assay with calcein, and electrophysiological and
      radiochemical assays, we show that Nramp1, similar to rat DMT1 (also known as
      SLC11A2), transports Fe(2+) and manganese, not Fe(3+) or copper. Metal ion
      transport is electrogenic and proton dependent. By contrast, Nramp2 transports
      only Fe(2+) in a non-electrogenic and proton-independent way. These differences
      reflect evolutionary divergence of the prototypical Nramp2 protein sequence
      compared to the archetypical Nramp1 and DMT1 proteins. 

PMID- 26208638
TI  - KCNK1 inhibits osteoclastogenesis by blocking the Ca2+ oscillation and JNK-NFATc1
      signaling axis.
AB  - KCNK1 (K(+) channel, subfamily K, member 1) is a member of the inwardly
      rectifying K(+) channel family, which drives the membrane potential towards the
      K(+) balance potential. Here, we investigated its functional relevance during
      osteoclast differentiation. KCNK1 was significantly induced during osteoclast
      differentiation, but its functional overexpression significantly inhibited
      osteoclast differentiation induced by RANKL (also known as TNFSF11), which was
      accompanied by the attenuation of the RANKL-induced Ca(2+) oscillation, JNK
      activation and NFATc1 expression. In contrast, KCNK1 knockdown enhanced the RANKL
      induced osteoclast differentiation, JNK activation and NFATc1 expression. In
      conclusion, we suggest that KCNK1 is a negative regulator of osteoclast
      differentiation; the increase of K(+) influx by its functional blockade might
      inhibit osteoclast differentiation by inhibiting Ca(2+) oscillation and the JNK
      NFATc1 signaling axis. Together with the increased attention on the
      pharmacological possibilities of using channel inhibition in the treatment of
      osteoclast-related disorders, further understanding of the functional roles and
      mechanisms of K(+) channels underlying osteoclast-related diseases could be
      helpful in developing relevant therapeutic strategies. 

PMID- 26208640
TI  - Follow-up C-reactive protein level is more strongly associated with outcome in
      stroke patients than admission levels.
AB  - The value of C-reactive protein (CRP) as a prognostic tool in stroke patients is
      unclear. The aim of this study is to explore the prognostic impact of CRP levels
      assessed at different time points on functional outcome in a large cohort of
      thrombolysed acute stroke patients. All thrombolysed stroke patients admitted to
      our department were entered in an open, prospective database. Clinical and
      demographic data were recorded. CRP was measured upon admission, within 24 h, and
      in the following days. Functional outcome was assessed using the modified Rankin
      Scale (mRS) at 3 months. Among 1242 thrombolysed patients, we found a
      statistically significant difference in median CRP values upon admission, within
      24 h, and follow-up with respect to outcome parameters (p < 0.001) including
      symptomatic intracerebral hemorrhage (sICH; p < 0.001). In regression models,
      follow-up CRP showed better predictive properties for outcome parameters compared
      to CRP assessed upon admission or within 24 h. The ROC analysis showed a good
      predictive value of follow-up CRP concerning dependent outcome [c-statistic 0.71
      (95 % CI 0.67-0.75) p < 0.001] and mortality [c-statistic 0.70 (95 % CI 0.66
      0.75) p < 0.001]. After adjustment for risk factors, follow-up CRP, but not
      admission CRP, was independently associated with dependent outcome (OR 2.67, 95 %
      CI 1.76-4.06; p < 0.001), mortality (OR 2.53, 95 % CI 1.50-4.25; p < 0.001), and
      sICH (OR 3.03, 95 % CI 1.51-6.06; p = 0.002). Follow-up CRP is strongly
      associated with functional outcome, sICH, and mortality after 90 days in
      thrombolysed stroke patients.

PMID- 26208639
TI  - Centrosomal AKAP350 and CIP4 act in concert to define the polarized localization
      of the centrosome and Golgi in migratory cells.
AB  - The acquisition of a migratory phenotype is central in processes as diverse as
      embryo differentiation and tumor metastasis. An early event in this phenomenon is
      the generation of a nucleus-centrosome-Golgi back-to-front axis. AKAP350 (also
      known as AKAP9) is a Golgi and centrosome scaffold protein that is involved in
      microtubule nucleation. AKAP350 interacts with CIP4 (also known as TRIP10), a
      cdc42 effector that regulates actin dynamics. The present study aimed to
      characterize the participation of centrosomal AKAP350 in the acquisition of
      migratory polarity, and the involvement of CIP4 in the pathway. The decrease in
      total or in centrosomal AKAP350 led to decreased formation of the nucleus
      centrosome-Golgi axis and defective cell migration. CIP4 localized at the
      centrosome, which was enhanced in migratory cells, but inhibited in cells with
      decreased centrosomal AKAP350. A decrease in the CIP4 expression or inhibition of
      the CIP4-AKAP350 interaction also led to defective cell polarization. Centrosome
      positioning, but not nuclear movement, was affected by loss of CIP4 or AKAP350
      function. Our results support a model in which AKAP350 recruits CIP4 to the
      centrosome, providing a centrosomal scaffold to integrate microtubule and actin
      dynamics, thus enabling centrosome polarization and ensuring cell migration
      directionality. 

PMID- 26208641
TI  - Role of computer-aided drug design in modern drug discovery.
AB  - Drug discovery utilizes chemical biology and computational drug design approaches
      for the efficient identification and optimization of lead compounds. Chemical
      biology is mostly involved in the elucidation of the biological function of a
      target and the mechanism of action of a chemical modulator. On the other hand,
      computer-aided drug design makes use of the structural knowledge of either the
      target (structure-based) or known ligands with bioactivity (ligand-based) to
      facilitate the determination of promising candidate drugs. Various virtual
      screening techniques are now being used by both pharmaceutical companies and
      academic research groups to reduce the cost and time required for the discovery
      of a potent drug. Despite the rapid advances in these methods, continuous
      improvements are critical for future drug discovery tools. Advantages presented
      by structure-based and ligand-based drug design suggest that their complementary
      use, as well as their integration with experimental routines, has a powerful
      impact on rational drug design. In this article, we give an overview of the
      current computational drug design and their application in integrated rational
      drug development to aid in the progress of drug discovery research. 

PMID- 26208643
TI  - The Aux/IAA gene rum1 involved in seminal and lateral root formation controls
      vascular patterning in maize (Zea mays L.) primary roots.

PMID- 26208642
TI  - High night temperature strongly impacts TCA cycle, amino acid and polyamine
      biosynthetic pathways in rice in a sensitivity-dependent manner.
AB  - Global climate change combined with asymmetric warming can have detrimental
      effects on the yield of crop plants such as rice (Oryza sativa L.). Little is
      known about metabolic responses of rice to high night temperature (HNT)
      conditions. Twelve cultivars with different HNT sensitivity were used to
      investigate metabolic changes in the vegetative stage under HNT compared to
      control conditions. Central metabolism, especially TCA cycle and amino acid
      biosynthesis, were strongly affected particularly in sensitive cultivars. Levels
      of several metabolites were correlated with HNT sensitivity. Furthermore, pool
      sizes of some metabolites negatively correlated with HNT sensitivity under
      control conditions, indicating metabolic pre-adaptation in tolerant cultivars.
      The polyamines putrescine, spermidine and spermine showed increased abundance in
      sensitive cultivars under HNT conditions. Correlations between the content of
      polyamines and 75 other metabolites indicated metabolic shifts from correlations
      with sugar-phosphates and 1-kestose under control to correlations with sugars and
      amino and organic acids under HNT conditions. Increased expression levels of ADC2
      and ODC1, genes encoding enzymes catalysing the first committed steps of
      putrescine biosynthesis, were restricted to sensitive cultivars under HNT.
      Additionally, transcript levels of eight polyamine biosynthesis genes were
      correlated with HNT sensitivity. Responses to HNT in the vegetative stage result
      in distinct differences between differently responding cultivars with a
      dysregulation of central metabolism and an increase of polyamine biosynthesis
      restricted to sensitive cultivars under HNT conditions and a pre-adaptation of
      tolerant cultivars already under control conditions with higher levels of
      potentially protective compatible solutes. 

PMID- 26208644
TI  - Multispectral airborne imagery in the field reveals genetic determinisms of
      morphological and transpiration traits of an apple tree hybrid population in
      response to water deficit.
AB  - Genetic studies of response to water deficit in adult trees are limited by low
      throughput of the usual phenotyping methods in the field. Here, we aimed at
      overcoming this bottleneck, applying a new methodology using airborne
      multispectral imagery and in planta measurements to compare a high number of
      individuals.An apple tree population, grafted on the same rootstock, was
      submitted to contrasting summer water regimes over two years. Aerial images
      acquired in visible, near- and thermal-infrared at three dates each year allowed
      calculation of vegetation and water stress indices. Tree vigour and fruit
      production were also assessed. Linear mixed models were built accounting for date
      and year effects on several variables and including the differential response of
      genotypes between control and drought conditions.Broad-sense heritability of most
      variables was high and 18 quantitative trait loci (QTLs) independent of the dates
      were detected on nine linkage groups of the consensus apple genetic map. For
      vegetation and stress indices, QTLs were related to the means, the intra-crown
      heterogeneity, and differences induced by water regimes. Most QTLs explained 15
      20% of variance.Airborne multispectral imaging proved relevant to acquire
      simultaneous information on a whole tree population and to decipher genetic
      determinisms involved in response to water deficit. 

PMID- 26208645
TI  - Hydrogen sulphide improves adaptation of Zea mays seedlings to iron deficiency.
AB  - Hydrogen sulphide (H2S) is emerging as a potential molecule involved in
      physiological regulation in plants. However, whether H2S regulates iron-shortage
      responses in plants is largely unknown. Here, the role of H2S in modulating iron
      availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient
      culture solution is reported. The main results are as follows: Firstly, NaHS, a
      donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings
      grown in iron-deficient culture solution. Secondly, electron micrographs of
      mesophyll cells from iron-deficient maize seedlings revealed plastids with few
      photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll
      chloroplasts appeared completely developed in H2S-treated maize seedlings.
      Thirdly, H2S treatment increased iron accumulation in maize seedlings by changing
      the expression levels of iron homeostasis- and sulphur metabolism-related genes.
      Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S
      treatment in seedlings grown in iron-deficient solution. Indeed, the gene
      expression of ferric-phytosiderophore transporter (ZmYS1) was specifically
      induced by iron deficiency in maize leaves and roots, whereas their abundance was
      decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis
      through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase
      large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the
      expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS),
      D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution.
      These results indicate that H2S is closely related to iron uptake, transport, and
      accumulation, and consequently increases chlorophyll biosynthesis, chloroplast
      development, and photosynthesis in plants. 

PMID- 26208646
TI  - Methylation mediated by an anthocyanin, O-methyltransferase, is involved in
      purple flower coloration in Paeonia.
AB  - Anthocyanins are major pigments in plants. Methylation plays a role in the
      diversity and stability of anthocyanins. However, the contribution of anthocyanin
      methylation to flower coloration is still unclear. We identified two homologous
      anthocyanin O-methyltransferase (AOMT) genes from purple-flowered (PsAOMT) and
      red-flowered (PtAOMT) Paeonia plants, and we performed functional analyses of the
      two genes in vitro and in vivo. The critical amino acids for AOMT catalytic
      activity were studied by site-directed mutagenesis. We showed that the
      recombinant proteins, PsAOMT and PtAOMT, had identical substrate preferences
      towards anthocyanins. The methylation activity of PsAOMT was 60 times higher than
      that of PtAOMT in vitro. Interestingly, this vast difference in catalytic
      activity appeared to result from a single amino acid residue substitution at
      position 87 (arginine to leucine). There were significant differences between the
      35S::PsAOMT transgenic tobacco and control flowers in relation to their chromatic
      parameters, which further confirmed the function of PsAOMT in vivo. The
      expression levels of the two homologous AOMT genes were consistent with
      anthocyanin accumulation in petals. We conclude that AOMTs are responsible for
      the methylation of cyanidin glycosides in Paeonia plants and play an important
      role in purple coloration in Paeonia spp. 

PMID- 26208647
TI  - Spatial distribution of centromeres and telomeres at interphase varies among
      Brachypodium species.
AB  - In this study the 3-D distribution of centromeres and telomeres was analysed in
      the interphase nuclei of three Brachypodium species, i.e. B. distachyon (2n=10),
      B. stacei (2n=20) and B. hybridum (2n=30), which is presumably a hybrid between
      the first two species. Using fluorescence in situ hybridization (FISH) with
      centromeric and telomeric DNA probes, it was observed that the majority of B.
      distachyon nuclei in the root tip cells displayed the Rabl configuration while
      both B. stacei and B. hybridum mostly lacked the centromere-telomere
      polarization. In addition, differentiated leaf cells of B. distachyon did not
      display the Rabl pattern. In order to analyse the possible connection between the
      occurrence of the Rabl pattern and the phase of cell cycle or DNA content, FISH
      was combined with digital image cytometry. The results revealed that the
      frequency of nuclei with the Rabl configuration in the root tip nuclei was
      positively correlated with an increase in DNA content, which resulted from DNA
      replication. Also, the analysis of the influence of the nuclear shape on the
      nuclear architecture indicated that an increasing elongation of the nuclei
      negatively affected the occurrence of the Rabl pattern. Some possible
      explanations of these phenomena are discussed. 

PMID- 26208649
TI  - Fabrication of photomasks consisting microlenses for the production of polymeric
      microneedle array.
AB  - A photomask consisting plano-convex microlenses for the production of polymeric
      microneedles was fabricated from a microinjection array. The microinjection array
      was first fabricated using photolithographical approach and subsequently
      assembled onto a polydimethylsiloxane (PDMS) stamp. Poly (ethylene glycol)
      diacrylate (PEGDA) solution was loaded into the microinjection stamp. The
      microinjection stamp was then applied onto a coverslip to dispense the polymer
      solution, producing liquid microdroplets. They were then irradiated to form plano
      convex microlenses. These microlenses were evaluated for their geometric
      properties and were fabricated into photomasks. The photomask consisting
      microlenses was used to fabricate polymeric microneedles that were evaluated and
      tested for skin penetration efficiency. 

PMID- 26208648
TI  - The Qb-SNARE Memb11 interacts specifically with Arf1 in the Golgi apparatus of
      Arabidopsis thaliana.
AB  - The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)
      proteins are critical for the function of the secretory pathway. The SNARE Memb11
      is involved in membrane trafficking at the ER-Golgi interface. The aim of the
      work was to decipher molecular mechanisms acting in Memb11-mediated ER-Golgi
      traffic. In mammalian cells, the orthologue of Memb11 (membrin) is potentially
      involved in the recruitment of the GTPase Arf1 at the Golgi membrane. However
      molecular mechanisms associated to Memb11 remain unknown in plants. Memb11 was
      detected mainly at the cis-Golgi and co-immunoprecipitated with Arf1, suggesting
      that Arf1 may interact with Memb11. This interaction of Memb11 with Arf1 at the
      Golgi was confirmed by in vivo BiFC (Bimolecular Fluorescence Complementation)
      experiments. This interaction was found to be specific to Memb11 as compared to
      either Memb12 or Sec22. Using a structural bioinformatic approach, several
      sequences in the N-ter part of Memb11 were hypothesized to be critical for this
      interaction and were tested by BiFC on corresponding mutants. Finally, by using
      both in vitro and in vivo approaches, we determined that only the GDP-bound form
      of Arf1 interacts with Memb11. Together, our results indicate that Memb11
      interacts with the GDP-bound form of Arf1 in the Golgi apparatus. 

PMID- 26208650
TI  - How far can we go with surgery in metastatic osteosarcoma patients?

PMID- 26208652
TI  - Self management for a man with asthma.

PMID- 26208653
TI  - Clarification of scope for Human Reproduction and Molecular Human Reproduction?.

PMID- 26208651
TI  - Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2
      Diabetes Mellitus.
AB  - RATIONALE: Accelerated arterial stiffening is a major complication of diabetes
      mellitus with no specific therapy available to date. OBJECTIVE: The present study
      investigates the role of the osteogenic transcription factor runt-related
      transcription factor 2 (Runx2) as a potential mediator and therapeutic target of
      aortic fibrosis and aortic stiffening in diabetes mellitus. METHODS AND RESULTS:
      Using a murine model of type 2 diabetes mellitus (db/db mice), we identify
      progressive structural aortic stiffening that precedes the onset of arterial
      hypertension. At the same time, Runx2 is aberrantly upregulated in the medial
      layer of db/db aortae, as well as in thoracic aortic samples from patients with
      type 2 diabetes mellitus. Vascular smooth muscle cell-specific overexpression of
      Runx2 in transgenic mice increases expression of its target genes, Col1a1 and
      Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly,
      increased Runx2 expression per se is not sufficient to induce aortic
      calcification. Using in vivo and in vitro approaches, we further demonstrate that
      expression of Runx2 in diabetes mellitus is regulated via a redox-sensitive
      pathway that involves a direct interaction of NF-kappaB with the Runx2 promoter.
      CONCLUSIONS: In conclusion, this study highlights Runx2 as a previously
      unrecognized inducer of vascular fibrosis in the setting of diabetes mellitus,
      promoting arterial stiffness irrespective of calcification.

PMID- 26208654
TI  - Strengthening sense of coherence: opportunities for theory building in health
      promotion.
AB  - Sense of coherence (SOC) reflects a coping capacity of people to deal with
      everyday life stressors and consists of three elements: comprehensibility,
      manageability and meaningfulness. SOC is often considered to be a stable entity
      that is developed in young adulthood and stabilizes around the age of 30. Recent
      studies have questioned this stability of SOC and some studies report on
      interventions that have been successful in strengthening SOC in adult
      populations. Currently, however, there is no clear understanding of the
      mechanisms underlying SOC. As a consequence, it is a challenge to determine what
      is needed in health promotion activities to strengthen SOC. This article aims to
      explore the mechanisms underlying SOC as these insights may underpin future
      health promotion efforts. An exploration of the salutogenic model suggests two
      important mechanisms: the behavioural and the perceptual. The behavioural
      mechanism highlights the possibility to empower people to use their resources in
      stressful situations. The perceptual mechanism suggests that, in order for people
      to deal with life stressors, it is essential that they are able to reflect on
      their understanding of the stressful situation and the resources that are
      available. Based on these mechanisms, we suggest that both empowerment and
      reflection processes, which are interdependent, may be relevant for health
      promotion activities that aim to strengthen SOC. The successful application of
      resources to deal with stressors is not only likely to have a positive influence
      on health, but also creates consistent and meaningful life experiences that can
      positively reinforce SOC levels.

PMID- 26208655
TI  - Seroprevalence studies of pertussis: what have we learned from different
      immunized populations.
AB  - Bordetella pertussis is a pathogen-causing whooping cough (pertussis) in humans.
      Although vaccination against the disease is effective, the bacterium is still
      circulating among population and can even cause death. Especially young infants,
      who lack protection, are vulnerable. The laboratory diagnostic methods to detect
      B. pertussis are culture, PCR and ELISA serology. Reported cases of the disease
      vary among countries but usually the incidence rates are low, <1 to 10/100 000.
      However, pertussis often goes unrecognized among patients as it presents itself
      like the common cold, especially in adults and elders who are often the source of
      the infection. This makes pertussis difficult to monitor and control. Serological
      surveillance is an easy manner to estimate the real burden of the disease among
      population. Furthermore, to have reliable results, anti-PT IgG antibodies should
      be measured, as PT is the only specific antigen to B. pertussis. This review aims
      to evaluate available pertussis seroprevalence studies throughout the world, and
      to compare the findings from countries with different vaccination histories and
      strategies. Estimation of the real burden of pertussis is compared to reported
      numbers. In addition, future aspects in seroprevalence studies are considered. 

PMID- 26208656
TI  - Power-Assisted Liposuction Mammaplasty (PALM): A New Technique for Breast
      Reduction.
AB  - BACKGROUND: Resection and reshaping of the parenchyma are common procedures to
      produce a natural breast shape in reduction mammaplasty and mastopexy. The
      challenges of these practices include maintaining sensitivity of the nipple
      areola complex (NAC), achieving upper-pole fullness, and preserving an adequate
      blood supply for patients with massive breast ptosis. OBJECTIVES: The authors
      describe their experience with power-assisted liposuction mammaplasty (PALM), a
      novel technique for breast reduction. METHODS: One hundred fifty consecutive
      women (300 breasts) who underwent PALM were evaluated in a prospective study.
      Minimizing skin undermining and glandular resection ensured maximal blood supply
      to the breast. A lateral pedicle was created to preserve NAC sensitivity. The
      transposed gland was contained within a large pocket made in the upper-inner
      quadrant. Glandular suspension sutures from the dermis to the chest wall
      stabilized the breast and recreated the inframammary fold. RESULTS: The mean
      distance from the nipple to the sternal notch was 36 cm, the mean NAC elevation
      was 16 cm, the mean lipoaspirate volume per breast was 650 cc, and the mean
      glandular resection mass per breast was 240 g. Complications included wound
      infection (6 of 300 breasts, 2%), wound dehiscence (3 breasts, 1%), and seroma (9
      breasts, 3%). Partial areolar necrosis occurred in 2 of 150 patients (1.3%), and
      9 patients (6%) underwent revisional surgery. CONCLUSIONS: PALM is a safe and
      reliable option for breast reduction and is indicated for patients with massive
      breast ptosis. LEVEL OF EVIDENCE 4: Therapeutic.

PMID- 26208658
TI  - A novel application of concentrated solar thermal energy in foundries.
AB  - Scrap preheating in foundries is a technology that saves melting energy, leading
      to economic and environmental benefits. The proposed method in this paper
      utilizes solar thermal energy for preheating scrap, effected through a parabolic
      trough concentrator that focuses sunlight onto a receiver which carries the
      metallic scrap. Scraps of various thicknesses were placed on the receiver to
      study the heat absorption by them. Experimental results revealed the pattern with
      which heat is gained by the scrap, the efficiency of the process and how it is
      affected as the scrap gains heat. The inferences from them gave practical
      guidelines on handling scraps for best possible energy savings. Based on the
      experiments conducted, preheat of up to 160  degrees C and a maximum efficiency
      of 70 % and a minimum efficiency of 40 % could be achieved across the time
      elapsed and heat gained by the scrap. Calculations show that this technology has
      the potential to save around 8 % of the energy consumption in foundries.
      Cumulative benefits are very encouraging: 180.45 million kWh of energy savings
      and 203,905 t of carbon emissions cut per year across the globe. This research
      reveals immense scope for this technology to be adopted by foundries throughout
      the world. 

PMID- 26208657
TI  - Histopathological Evidence of Adventitial or Medial Injury Is a Strong Predictor
      of Restenosis During Directional Atherectomy for Peripheral Artery Disease.
AB  - PURPOSE: To investigate the impact on restenosis rates of deep injury to the
      adventitial layer during directional atherectomy. METHODS: Between 2007 and 2010,
      116 consecutive patients (mean age 69.6 years; 56 men) with symptomatic
      femoropopliteal stenoses were treated with directional atherectomy at a single
      center. All patients had claudication and TASC A/B lesions in the superficial
      femoral or popliteal arteries. Histopathology analysis of atherectomy specimens
      was performed to identify adventitial injury. Clinical follow-up included
      physical examination and duplex ultrasound scans at 3, 6, and 12 months in all
      patients. The primary endpoint was the duplex-documented 1-year rate of
      restenosis, which was determined by a peak systolic velocity ratio <2.4. Patients
      were dichotomized by the presence or absence of adventitial or medial cuts as
      evaluated by histopathology. RESULTS: Adventitial injury were identified in 62
      (53%) of patients. There were no differences in baseline demographic and clinical
      features (p>0.05), lesion length (58.7+/-12.8 vs 56.2+/-13.6 mm, p=0.40), or
      vessel runoff (1.9+/-0.6 vs 2.0+/-0.6, p=0.37) between patients with and without
      adventitial injury, respectively. The overall 1-year incidence of restenosis was
      57%, but the rate was significantly higher (p<0.0001) in patients with
      adventitial or medial injury (97%, 60/62) as compared with those without (11%,
      6/54). CONCLUSION: Lack of adventitial injury after atherectomy for
      femoropopliteal stenosis is strongly related to patency at 1 year.

PMID- 26208659
TI  - An artificially constructed Syngonium podophyllum-Aspergillus niger combinate
      system for removal of uranium from wastewater.
AB  - Aspergillus niger was inoculated to the roots of five plants, and the Syngonium
      podophyllum-A. niger combinate system (SPANCS) was found to be the most effective
      in removing uranium from hydroponic liquid with initial uranium concentration of
      5 mg L(-1). Furthermore, the hydroponic experiments on the removal of uranium
      from the hydroponic liquids with initial uranium concentrations of 0.5, 1.0, and
      3.0 mg L(-1) by the SPANCS were conducted, the inhibitory effect of A. niger on
      the growth of S. podophyllum in the SPANCS was studied, the accumulation
      characteristics of uranium by S. podophyllum in the SPANCS were analyzed, and the
      Fourier transform infrared (FT-IR) and extended X-ray absorption fine structure
      (EXAFS) spectra were measured. The results show that the removal of uranium by
      the SPANCS from the hydroponic liquids with initial uranium concentrations of
      0.5, 1.0, and 3.0 mg L(-1) reached 98.20, 97.90, and 98.50%, respectively, after
      37 days of accumulation of uranium; that the uranium concentrations in the
      hydroponic liquids decreased to 0.009, 0.021, and 0.045 mg L(-1), respectively,
      which are lower than the stipulated concentration for discharge of 0.050 mg L(-1)
      by the People's Republic of China; that A. niger helped to generate more groups
      in the root of S. podophyllum which can improve the complexing capability of S.
      podophyllum for uranium; and that the uranium accumulated in the root of S.
      podophyllum was in the form of phosphate uranyl and carboxylic uranyl.

PMID- 26208660
TI  - Determination of 2,8-dichlorodibenzo-p-dioxin in toothpaste and mouthwash
      consumer products using GC-MS.
AB  - A gas chromatography-mass spectrometry (GC-MS) method was developed for the
      identification and quantification of 2,8-dichlorodibenzo-p-dioxin (2,8-DCDD) in
      toothpaste and mouthwash consumer products. Liquid-liquid extraction and solid
      phase extraction were used in the sample preparation. The limit of detection was
      0.96 ng/g in toothpaste and 0.83 ng/g in mouthwash. The accuracy represented by
      relative errors was less than 12.5%. The intra-day and inter-day precision, which
      are represented by the relative standard deviation values, were within 11.2 and
      10.6%, respectively. The method was successfully applied to analyze 2,8-DCDD in
      toothpaste and mouthwash products, as well as that from the photo-degradation of
      triclosan spiked in both sample matrix.

PMID- 26208661
TI  - Distribution behavior and risk assessment of metals in bio-oils produced by
      liquefaction/pyrolysis of sewage sludge.
AB  - The distribution behaviors of metals in bio-oils derived from sewage sludge (SS)
      by liquefaction with different solvents (ethanol, methanol, or acetone) and by
      pyrolysis at different temperatures (550-850  degrees C) were investigated. The
      concentrations of crust metals (K, Na, Ca, Mg, Fe, and Al) in bio-oils were much
      higher than those of the anthropogenic metals (Cu, Zn, Pb, Cd, Cr, Ni, V, Mn, Ba,
      Co, Ti, Sn, As, and Hg), but the anthropogenic metals were more inclined to
      distribute in bio-oil phase compared with crust metals. The anthropogenic metals
      in bio-oils can be divided in three groups in terms of the distribution
      similarities according to Cluster analysis: (A) Cu, Co, Ni, V, and Sn; (B) Cr,
      Ti, Mn, and Ba; (C) Pb, Cd, As, Hg, and Zn. Cu, Cr, Hg, Cd, V, Co, and Sn
      distributed in the liquefaction/pyrolysis bio-oils accounted for as high as 5-20%
      of the metals in SS and were evaluated "moderate enrichment" by the enrichment
      factors method. According to the potential ecological risk index (PERI) method,
      Hg presented very high risk, Cu presented moderate risk, and Cd presented low to
      moderate risk; and the overall risk levels of these bio-oils were very high risk
      (except P550, presented considerable risk).

PMID- 26208662
TI  - Synchrotron micro-scale study of trace metal transport and distribution in
      Spartina alterniflora root system in Yangtze River intertidal zone.
AB  - This study is focused on micro-scale measurement of metal (Ca, Cl, Fe, K, Mn, Cu,
      Pb, and Zn) distributions in Spartina alterniflora root system. The root samples
      were collected in the Yangtze River intertidal zone in July 2013. Synchrotron X
      ray fluorescence (XRF), computed microtomography (CMT), and X-ray absorption near
      edge structure (XANES) techniques, which provide micro-meter scale analytical
      resolution, were applied to this study. Although it was found that the metals of
      interest were distributed in both epidermis and vascular tissue with the varying
      concentrations, the results showed that Fe plaque was mainly distributed in the
      root epidermis. Other metals (e.g., Cu, Mn, Pb, and Zn) were correlated with Fe
      in the epidermis possibly due to scavenge by Fe plaque. Relatively high metal
      concentrations were observed in the root hair tip. This micro-scale investigation
      provides insights of understanding the metal uptake and spatial distribution as
      well as the function of Fe plaque governing metal transport in the root system. 

PMID- 26208663
TI  - Toxicological effects, mechanisms, and implied toxicity thresholds in the roots
      of Vicia faba L. seedlings grown in copper-contaminated soil.
AB  - Copper (Cu) contamination has become a global concern because of industrial,
      agricultural, and other anthropogenic activities. In the present experiments, the
      toxicological effects, mechanisms, and potential toxicity thresholds were
      investigated in the roots of Vicia faba L. seedlings that were cultivated in Cu
      amended soils (0, 6.25, 12.5, 25, 50, 100, 200, 400, and 600 mg kg(-1)) for 20
      days, based on an analysis of the soil physicochemical properties, native Cu,
      available Cu, and root-enriched Cu contents. The superoxide dismutase (SOD),
      ascorbate peroxidase (APX), and guaiacol peroxidase (POD) isozymes and
      activities, as well as glutathione (GSH) and heat shock protein 70 (HSP70),
      changed like biphasic dose-response curves, cooperating to control the redox
      homeostasis. The APX and POD enzymes exhibited enhanced activities and became
      H2O2 scavengers primarily when the catalase (CAT) activities tended to decrease.
      Endoprotease (EP) isozymes and activities might be enhanced to degrade
      carbonylated proteins and alleviate metabolic disturbance in the roots.
      Additionally, HSP70 may not be suitable as a biomarker for relatively higher soil
      Cu concentrations and relatively longer exposure times for the roots. As a
      result, the isozymes and activities of SOD, CAT, and EP, as well as GSH, can be
      adopted as the most sensitive biomarkers. The toxicity threshold is estimated as
      0.76-1.21 mg kg(-1) of available Cu in the soils or 25.04-36.65 MUg Cu g(-1) dry
      weights (DW) in the roots. 

PMID- 26208664
TI  - Survey of 11 mycotoxins in wheat flour in Hebei province, China.
AB  - A survey of 11 mycotoxins in 348 wheat flour samples marketed in Hebei province
      of China were analysed by liquid chromatography-tandem mass spectrometry, was
      carried out. The selected mycotoxins consisted of four aflatoxins (AFs: AFB1,
      AFB2, AFG1 and AFG2) and seven Fusarium toxins, i.e. deoxynivalenol (DON),
      nivalenol, 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol, zearalenone,
      Fusarenon-X and deoxynivalenol-3-glucoside. Results indicated that most of the
      wheat samples analysed were contaminated with mycotoxins. Wheat was most
      susceptible to DON (91.4% contamination), with a mean level of 240 MUg kg(-1). On
      average the probable daily intake (PDI, expressed as ug kg(-1) body weight day(
      1)) of mycotoxins was within the provisional maximum tolerable daily intake
      (PMTDI, 2.0 ug kg(-1) of body weight day(-1)) as set by the Joint FAO/WHO Expert
      Committee on Food Additives. Nevertheless, exposure assessment revealed that the
      maximum PDI of mycotoxins was 4.06 ug kg(-1) body weight day(-1), which was twice
      the PMTDI value. Thus, consistent monitoring is recommended, as to keep the
      contamination level under control. 

PMID- 26208666
TI  - Myelodysplastic syndromes in Chernobyl clean-up workers.
AB  - The studies of the recent decades posed the question of the association between
      radiation exposure and myelodysplastic syndromes (MDS). This association has been
      proved in secondary MDS originating upon exposure to chemotherapeutics and/or
      radiation therapy. The long-term study in Japanese atomic (A)-bomb survivors
      demonstrated the significant linear dose-response for MDS confirming the link
      between radiation exposure and this form of hematopoietic malignancies. All these
      findings provide the strong basis for studying MDS in the persons exposed to
      radiation following the Chernobyl disaster, especially those in the cohort of
      Chernobyl clean-up workers of 1986-1987. The data on MDS among Chernobyl clean-up
      workers (1986-1987) diagnosed in 1996-2012 at the reference laboratory of RE
      Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology are
      summarized. MDS cases were diagnosed in 23 persons (21 males and 2 females)
      having been exposed to radiation as clean-up workers of 1986-1987. Refractory
      anemia (RA) has been detected in 13, refractory anemia with ring sideroblasts
      (RARS)-in 2, and refractory anemia with excess blasts (RAEB)-in 8 patients. The
      median age of those MDS patients was 62.0 years. In addition, 5 cases of chronic
      myelomonocytic leukemia (CMML) were recorded in the group of Chernobyl clean-up
      workers with the median time of 14.8 years from 1986-1987 to diagnosis. The
      association between radiation exposure and MDS is discussed. The suggested life
      long risk for myelodysplastic syndromes among A-bomb survivors in Japan
      highlights the importance of the continuing follow-up studies in the affected
      populations in the post-Chernobyl period. 

PMID- 26208665
TI  - Recent Advances in Fungal Hydrophobin Towards Using in Industry.
AB  - Fungal hydrophobin is a family of low molecular weight proteins consisting of
      four disulfide bridges and an extraordinary hydrophobic patch. The hydrophobic
      patch of hydrophobins and the molecules of gaseous CO2 may interact together and
      form the stable CO2-nanobubbles covered by an elastic membrane in carbonated
      beverages. The nanobubbles provide the required energy to provoke primary
      gushing. Due to the hydrophobicity of hydrophobin, this protein is used as a
      biosurfactant, foaming agent or encapsulating agent in food products and medicine
      formulations. Increasing demands for using of hydrophobins led to a challenge
      regarding production and purification of this product. However, the main issue to
      use hydrophobin in the industry is the regulatory affairs: yet there is no
      approved legislation for using hydrophobin in food and beverages. To comply with
      the legislation, establishing a consistent method for obtaining pure hydrophobins
      is necessary. Currently, few research teams in Europe are focusing on different
      aspects of hydrophobins. In this paper, an up-to-date collection of highlights
      from those special groups about the bio-chemical and physicochemical
      characteristics of hydrophobins have been studied. The recent advances of those
      groups concerning the production and purification, positive applications and
      negative function of hydrophobin are also summarised. 

PMID- 26208667
TI  - Evaluation of soluble interleukin-2 receptor and serum lactate dehydrogenase in
      malignant lymphoma.

PMID- 26208668
TI  - Relationship Between Prehypertension/Hypertension and Periodontal Disease: A
      Prospective Cohort Study.
AB  - BACKGROUND: Most cross-sectional studies have found a significant positive
      relationship between periodontal disease and prehypertension/hypertension.
      However, these studies had limitations and there are few prospective cohort
      studies in young adults. The purpose of this prospective cohort study was to
      investigate whether periodontal disease was related to
      prehypertension/hypertension in Japanese university students. METHODS: Students
      (n = 2,588), who underwent health examinations before entering university and
      before graduation, were included in the analysis. The association between
      periodontal disease such as the percentage of bleeding on probing (BOP) and
      community periodontal index (CPI) scores, and change in blood pressure status was
      determined. RESULTS: At the reexamination, the numbers of participants with
      prehypertension (systolic blood pressure 120-139mm Hg or diastolic blood pressure
      80-89mm Hg) and hypertension (>=140/90mm Hg) were 882 (34.1%) and 109 (4.2%),
      respectively. In a logistic regression model, the risk of hypertension was
      significantly associated with male (odds ratio (OR): 6.31; 95% confidence
      interval (CI): 2.63-15.13; P < 0.001), no habitual physical activity at baseline
      (OR: 2.90; 95% CI: 1.56-5.38; P < 0.01) and periodontal disease defined as the
      presence of both probing pocket depth (PPD) >= 4mm and BOP >= 30% at baseline
      (OR: 2.74; 95% CI: 1.19-6.29; P = 0.02) in participants with prehypertension at
      baseline. On the other hand, the risk of prehypertension was not associated with
      presence of periodontal disease (OR: 0.93; 95% CI: 0.51-1.70; P = 0.82).
      CONCLUSION: In the short-term prospective cohort study, a significant association
      between presence of periodontal disease and hypertension was observed in Japanese
      university students.

PMID- 26208669
TI  - Response to "Circadian Arterial Blood Pressure Variation and Glaucoma
      Progression: More Questions Than Answers?

PMID- 26208670
TI  - Nocturnal Intermittent Hypoxia Is Associated With Left Ventricular Hypertrophy in
      Middle-Aged Men With Hypertension and Obstructive Sleep Apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) and left ventricular (LV) hypertrophy
      are considered to be closely associated. However, the relationship has not yet
      been fully demonstrated and is hence still controversial. The purpose of this
      study was to assess in hypertensive male patients the relationship between OSA
      and cardiac structure using a new index, namely, integrated area of desaturation
      (IAD), in addition to the apnea-hypopnea index (AHI) that is currently the most
      frequently used index of sleep-disordered breathing. METHODS: In our cross
      sectional study, 223 hypertensive men younger than 65 years with sleep apnea and
      normal cardiac function were enrolled. All subjects were evaluated by fully
      attended polysomnography. Cardiac structure and function were evaluated by
      echocardiography. RESULTS: LV mass index significantly correlated with IAD (r =
      0.203, P < 0.05), but not with AHI. Multivariate linear regression analyses
      showed that IAD, brain natriuretic peptide (BNP), and age are independent
      variables affecting the LV mass index (beta = 0.262, 0.237, and 0.173,
      respectively, P < 0.05). IAD was the one and only determinant among the indices
      of sleep-disordered breathing. CONCLUSIONS: Nocturnal intermittent hypoxia
      defined by IAD may be associated with LV hypertrophy in men with well-controlled
      hypertension and obstructive sleep apnea.

PMID- 26208671
TI  - High Prevalence of Hypertension in a Danish Population Telemedical Home
      Measurement of Blood Pressure in Citizens Aged 55-64 Years in Holstebro County.
AB  - BACKGROUND: Home blood pressure (HBP) is prognostically superior to office BP
      (OBP) and similar to ambulatory BP measurements. We determined the prevalence of
      hypertension using HBP with telemedical data transmission in the municipality of
      Holstebro, Denmark (57,000 citizens). METHODS: Using the Civil Registration
      System, we invited citizens aged 55-64 years to have their OBP and HBP measured
      using telemedical data transmission. Elevated OBP was defined as >=140/90mm Hg.
      HBP was measured 3 times daily on 3 consecutive days with 3 measurements on each
      occasion. HBP was the mean of all measurements on day 1 and 3, and hypertension
      was defined as >=135/85mm Hg. RESULTS: We included 3,102 citizens who had
      performed at least 12 HBP measurements during day 2 and 3. Group 1: (n = 1,464,
      47%) had both normal OBP and HBP. Group 2: (n = 838, 27%) had both elevated OBP
      and HBP indicating persistent hypertension. Group 3: (n = 560, 18%) had elevated
      OBP and normal HBP indicating white coat hypertension (WCH). Group 4: (n = 240,
      8%) had normal OBP and elevated HBP indicating masked hypertension (MH). Thus,
      1,078 (35%, groups 2 and 4) were untreated or insufficiently treated. Awareness
      of hypertension was registered in 950 patients (31%) and of these 49% had a
      normal HBP. CONCLUSIONS: This is the first large-scale study to eliminate
      completely reporting bias by using telemedical transmission of BP data. One third
      of citizens in the age group 55-64 years had an abnormally high HBP, and one
      fourth either had WCH or MH. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov
      identification number: NCT02355392.

PMID- 26208672
TI  - Association of Nocturnal Hypertension With Disease Activity in Rheumatoid
      Arthritis.
AB  - OBJECTIVES: Both nocturnal hypertension (HT) and systemic inflammation underlying
      rheumatoid arthritis (RA) have been shown to be independent predictors of
      cardiovascular disease (CVD), although little is known on the relationship
      between nocturnal blood pressure (BP) and disease activity in RA patients.
      METHODS: We performed 24-hour ambulatory BP monitoring (ABPM) in 71 RA patients
      to examine the relationship of nocturnal fall in BP and RA disease activity based
      on a disease activity score of 28 joint counts with C-reactive protein (CRP, 28
      joint disease activity score (DAS28)-CRP). Among them, 25 RA patients whose
      consent obtained were reexamined by ABPM to assess the improvement of nocturnal
      fall in BP after RA therapeutic intervention. RESULTS: The mean DAS28-CRP level
      was 4.8+/-1.6 in 71 RA patients. The mean nocturnal fall in BP was 5.6+/-8.9%.
      DAS28-CRP was associated significantly and independently in a negative manner
      with the nocturnal fall in BP (beta = -0.388, P = 0.004). In 25 RA patients,
      DAS28-CRP improved from 5.4+/-1.1 to 3.5+/-0.8 (P < 0.0001) and the nocturnal
      fall in BP increased significantly from 4.5+/-9.2% to 10.6+/-5.8% (P = 0.002)
      with the significant decrease of nighttime systolic BP (SBP) from 121.2+/-22.5mm
      Hg to 112.5+/-18.8mm Hg (P = 0.02) in spite of no change in daytime BP after 4
      weeks of RA treatment. CONCLUSIONS: The present study observed that higher RA
      activity was associated with lower nocturnal fall in BP, but not daytime BP, in
      RA patients.

PMID- 26208673
TI  - Reduction of Central Blood Pressure in Response to Oral Glucose Loading Is
      Blunted in Patients With Diabetes Mellitus.
AB  - BACKGROUND: Recent studies have shown that arterial stiffness is reduced after
      meal intake. We evaluated the acute response of central hemodynamics to glucose
      loading and the variation in their responses among normal glucose tolerance
      (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM). METHODS: The
      study enrolled 85 patients with known or suspected coronary artery disease who
      underwent a 75-g oral glucose tolerance test. Central hemodynamic measurements
      were assessed using radial applanation tonometry at fasting, 60, and 120 minutes
      after glucose loading. RESULTS: Glucose loading decreased the augmentation index
      normalized to a heart rate of 75 bpm (AIx@75) (81.6+/-13.9 to 74.5+/-14.1%, P <
      0.01) and central systolic blood pressure (SBP) (115+/-22 to 109+/-21mm Hg, P <
      0.01) at 120 minutes without a significant change in brachial SBP (126+/-25 to
      125+/-25mm Hg, P = 0.93). Glucose loading decreased central SBP in NGT and IGT
      groups but did not affect the DM group. Change in AIx@75 at 120 minutes after
      glucose loading was blunted in IGT and DM groups compared with the NGT group (
      5.7+/-4.4 vs. -3.6+/-4.1 vs. -9.3+/-6.2%, P < 0.01). Multivariate logistic
      regression analysis identified DM as an independent factor associated with the
      presence of blunted response of AIx to glucose loading. CONCLUSIONS: Oral glucose
      loading decreased central SBP and AIx@75 without a significant change in brachial
      SBP, and these central hemodynamic responses were blunted in patients with DM.

PMID- 26208674
TI  - Change in Systolic Blood Pressure During Stroke, Functional Status, and Long-Term
      Mortality in an Elderly Population.
AB  - BACKGROUND: Elevated systolic blood pressure (SBP) recorded by 24-hour blood
      pressure monitoring (24H BPM) on the first day of acute stroke is associated in
      elderly patients, with an unfavorable outcome. Herein, we assessed, by 24H BPM,
      the impact of the change in SBP levels during the first week of stroke on short
      term functional status and long-term mortality in elderly patients. METHODS: One
      hundred and fifty acute stroke patients (69 males), mean age at admission 83.6+/
      5.5 years, 82% with ischemic stroke, were investigated. 24H BPM was recorded
      within 24 hours of admission and 1 week later. After 7 days, patients were
      assessed for functional status according to the modified Rankin scale (mRS) and
      were subsequently followed for mortality up to 7.5 years (mean 3.16+/-2.29).
      RESULTS: After 7 days, SBP decreased from 147+/-21 to 140+/-20 mm Hg (P < 0.001).
      Functional status improved and mRS decreased from 4.2 to 3.7. During follow-up,
      58 patients (17 males and 41 females) had died. Mortality rate was higher in
      females (69% vs. 45%; P < 0.01) and in patients with a history of congestive
      heart failure. The average admission SBP predicted short-term functional status
      and long-term mortality. However, the change in SBP corrected for admission
      levels, gender, age and other variables was not associated with short-term
      functional status and long-term mortality. CONCLUSION: There is no evidence of
      association between change in SBP during the first week of stroke and short-term
      functional status and long-term mortality in this group of stroke patients.

PMID- 26208675
TI  - Towards a person-centered approach to the developmental psychopathology of
      trauma.

PMID- 26208676
TI  - Monomerization alters the dynamics of the lid region in Campylobacter jejuni
      CstII: an MD simulation study.
AB  - CstII, a bifunctional (alpha2,3/8) sialyltransferase from Campylobacter jejuni,
      is a homotetramer. It has been reported that mutation of the interface residues
      Phe121 (F121D) or Tyr125 (Y125Q) leads to monomerization and partial loss of
      enzyme activity, without any change in the secondary or tertiary structures. MD
      simulations of both tetramer and monomer, with and without bound donor substrate,
      were performed for the two mutants and WT to understand the reasons for partial
      loss of activity due to monomerization since the active site is located within
      each monomer. RMSF values were found to correlate with the crystallographic B
      factor values indicating that the simulations are able to capture the flexibility
      of the molecule effectively. There were no gross changes in either the secondary
      or tertiary structure of the proteins during MD simulations. However, interface
      is destabilized by the mutations, and more importantly the flexibility of the lid
      region (Gly152-Lys190) is affected. The lid region accesses three major
      conformations named as open, intermediate, and closed conformations. In both
      Y121Q and F121D mutants, the closed conformation is accessed predominantly. In
      this conformation, the catalytic base His188 is also displaced. Normal mode
      analysis also revealed differences in the lid movement in tetramer and monomer.
      This provides a possible explanation for the partial loss of enzyme activity in
      both interface mutants. The lid region controls the traffic of substrates and
      products in and out of the active site, and the dynamics of this region is
      regulated by tetramerization. Thus, this study provides valuable insights into
      the role of loop dynamics in enzyme activity of CstII. 

PMID- 26208677
TI  - When everyday life becomes a storm on the horizon: families' experiences of good
      mental health while hiking in nature.
AB  - Hiking in nature is often presented as a yearning for lost harmony premised on an
      alleged divide between nature as authentically healthy and society as polluted.
      This paper's aim is to question this strict divide and the strong belief in
      nature as having an innate health-providing effect, the biophilia hypothesis, by
      examining what Norwegian families with young children experience when walking in
      the forest. Twenty-four conversations with families during a hiking trip in the
      forest were recorded, and the data were analysed with Giorgi's descriptive
      phenomenological research method. The paper introduces the general descriptive
      meaning structure of the phenomenon 'family-hiking with young children'. It shows
      that a hiking trip clears space for the family in their everyday lives which is
      largely dominated by relations with non-family members at both work and leisure.
      The families experience that they actively generate a different existence with a
      sense of here-and-now presences that can strengthen core family relations and
      also provide the opportunity to pass down experiences that can be recollected and
      realized by future generations. This experience is complex and constituted by
      social practices, which indicate that the biophilia hypothesis seems to be an
      insufficient explanation of why families go hiking in nature. Nature rather
      represents a peaceful background that allows for the perpetuation of the family
      as a social institution and the recreation of cohesion in everyday life. 

PMID- 26208679
TI  - Visualization of Nanofibrillar Cellulose in Biological Tissues Using a
      Biotinylated Carbohydrate Binding Module of beta-1,4-Glycanase.
AB  - Nanofibrillar cellulose is a very promising innovation with diverse potential
      applications including high quality paper, coatings, and drug delivery carriers.
      The production of nanofibrillar cellulose on an industrial scale may lead to
      increased exposure to nanofibrillar cellulose both in the working environment and
      the general environment. Assessment of the potential health effects following
      exposure to nanofibrillar cellulose is therefore required. However, as
      nanofibrillar cellulose primarily consists of glucose moieties, detection of
      nanofibrillar cellulose in biological tissues is difficult. We have developed a
      simple and robust method for specific and sensitive detection of cellulose
      fibers, including nanofibrillar cellulose, in biological tissue, using a
      biotinylated carbohydrate binding module (CBM) of beta-1,4-glycanase (EXG:CBM)
      from the bacterium Cellulomonas fimi. EXG:CBM was expressed in Eschericia coli,
      purified, and biotinylated. EXG:CBM was shown to bind quantitatively to five
      different cellulose fibers including four different nanofibrillar celluloses.
      Biotinylated EXG:CBM was used to visualize cellulose fibers by either
      fluorescence- or horse radish peroxidase (HRP)-tagged avidin labeling. The HRP
      EXG:CBM complex was used to visualize cellulose fibers in both cryopreserved and
      paraffin embedded lung tissue from mice dosed by pharyngeal aspiration with 10
      200 MUg/mouse. Detection was shown to be highly specific, and the assay appeared
      very robust. The present method represents a novel concept for the design of
      simple, robust, and highly specific detection methods for the detection of
      nanomaterials, which are otherwise difficult to visualize. 

PMID- 26208678
TI  - Hepatitis B and A vaccination in HIV-infected adults: A review.
AB  - Hepatitis B and A account for considerable morbidity and mortality worldwide.
      Immunization is the most effective means of preventing hepatitis B and A.
      However, the immune response to both hepatitis vaccines seems to be reduced in
      HIV-infected subjects. The aim of this review was to analyze the immunogenicity,
      safety, long-term protection and current recommendations of hepatitis B and A
      vaccination among HIV-infected adults. The factors most frequently associated
      with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those
      related to immunosuppression (CD4 level and HIV RNA viral load) and to the
      frequency of administration and/or the amount of antigenic load per dose. The
      duration of the response to both HBV and HAV vaccines is associated with
      suppression of the viral load at vaccination and, in the case of HBV vaccination,
      with a higher level of antibodies after vaccination. In terms of safety, there is
      no evidence of more, or different, adverse effects compared with HIV-free
      individuals. Despite literature-based advice on the administration of alternative
      schedules, revaccination after the failure of primary vaccination, and the need
      for periodic re-evaluation of antibody levels, few firm recommendations are found
      in the leading guidelines. 

PMID- 26208680
TI  - Are our cornea waiting lists dynamic enough?
AB  - The purpose of this study was to evaluate the dynamic reality of the corneal
      transplant (CT) waiting list and if the CT candidates are really eager to
      operation. We evaluated the response of consecutive 96 CT candidates to call for
      operation. The age, functional visual acuity, CT indication, waiting period, and
      the excuse of refusal for candidates that postponed the operation were also
      evaluated. The patients were classified into two groups according to the
      availability (Group 1, available; Group 2, unavailable). To find an available
      candidate for transplantation of 48 consecutive corneal tissues, 96 patients had
      to be called. The mean age of the patients was 57.49 +/- 18.75. The mean age of
      Group 1 and Group 2 was 54.28 +/- 18.12 (13-80) and 60.44 +/- 19.01 (9-88) years,
      respectively (p = 0.108). It was found that the call refusal was higher in
      patients elder than age 70 (p = 0.04). The mean time between being added to the
      list and the call was 22.96 +/- 7.80 (9-39) months for Group 1, 27.02 +/- 8.25 (9
      53) months for Group 2 (p = 0.015). The estimation point for waiting period was
      22 months (p = 0.044). The most common reasons of excuse were inconvenience of
      timing, giving up operation, and secondary health problems, whereas anticoagulant
      use was the most common reason for postponement. As the waiting period gets
      longer and CT candidates get older, they tend to give up operation. The secondary
      health problems and use of systemic anticoagulants are important problems that
      might cause postponing the CT surgery and ruin the dynamicity of the waiting
      lists. 

PMID- 26208681
TI  - Structure of yeast Ape1 and its role in autophagic vesicle formation.
AB  - In Saccharomyces cerevisiae, a constitutive biosynthetic transport pathway,
      termed the cytoplasm-to-vacuole targeting (Cvt) pathway, sequesters precursor
      aminopeptidase I (prApe1) dodecamers in the form of a large complex into a Cvt
      vesicle using autophagic machinery, targeting it into the vacuole (the yeast
      lysosome) where it is proteolytically processed into its mature form, Ape1, by
      removal of an amino-terminal 45-amino acid propeptide. prApe1 is thought to serve
      as a scaffolding cargo critical for the assembly of the Cvt vesicle by presenting
      the propeptide to mediate higher-ordered complex formation and autophagic
      receptor recognition. Here we report the X-ray crystal structure of Ape1 at 2.5 A
      resolution and reveal its dodecameric architecture consisting of dimeric and
      trimeric units, which associate to form a large tetrahedron. The propeptide of
      prApe1 exhibits concentration-dependent oligomerization and forms a stable
      tetramer. Structure-based mutagenesis demonstrates that disruption of the inter
      subunit interface prevents dodecameric assembly and vacuolar targeting in vivo
      despite the presence of the propeptide. Furthermore, by examining the vacuolar
      import of propeptide-fused exogenous protein assemblies with different quaternary
      structures, we found that 3-dimensional spatial distribution of propeptides
      presented by a scaffolding cargo is essential for the assembly of the Cvt vesicle
      for vacuolar delivery. This study describes a molecular framework for
      understanding the mechanism of Cvt or autophagosomal biogenesis in selective
      macroautophagy. 

PMID- 26208682
TI  - Quantification of tricuspid regurgitation using two-dimensional velocity encoding
      cine: optimal plane and reproducibility.
AB  - To determine the optimal plane of two-dimensional velocity-encoding cine (VENC)
      magnetic resonance (MR) imaging at the tricuspid annulus for quantification of
      tricuspid regurgitation (TR) and to assess the reproducibility of VENC tricuspid
      flow measurements. We conducted a retrospective review of MR images of 25
      consecutive patients (M:F = 8:17; mean age, 58.5 +/- 10.5 years) with TR. VENC
      was performed twice orthogonal to the tricuspid annulus plane during the end
      diastolic (ED) and end-systolic (ES) phases. The TR fraction was quantified at
      each plane as retrograde flow/antegrade flow and additionally as retrograde flow
      of the ED plane/antegrade flow of the ES plane (combined plane method). The
      conventional method to determine the TR amount [right ventricular stroke volume
      (RVSV)-pulmonary antegrade flow] and TR fraction (TR amount/RVSV) was used as the
      reference standard. There were no differences between TR amount and retrograde
      flow of the ED plane (65.3 +/- 43.4 vs. 70.5 +/- 36.1 ml, P = 0.361) between the
      RVSV and the antegrade flow of the ES phase (124.2 +/- 46.1 vs. 128.0 +/- 45.0
      ml, P = 0.612) or in TR fraction between the conventional and combined plane
      methods (48.8 +/- 19.2 vs. 56.3 +/- 24.3 %, P = 0.08). The retrograde flow of the
      ED phase was best correlated with TR amount [intraclass correlation coefficient
      (ICC) = 0.859] and antegrade flow of ES with RVSV (ICC = 0.808). The TR fraction
      of the combined plane method was best correlated with the conventional method
      (ICC = 0.694). Interobserver agreement of VENC flow measurements was excellent
      (ICC, 0.939-0.993). The optimal method for quantification of TR using tricuspid
      annular VENC was the combined plane method, which divides the retrograde flow of
      the ED plane by the antegrade flow of the ES plane. Tricuspid flow measurements
      using VENC showed excellent reproducibility. 

PMID- 26208683
TI  - Angiographic result of index PCI determines the presence of right ventricular
      infarction in patients with acute inferior myocardial infarction.
AB  - It is still a matter of debate which patients with acute inferior myocardial
      infarction are at increased risk of developing right ventricular (RV) myocardial
      infarction (RVMI). Cardiac magnetic resonance imaging (CMRI) with late
      enchancement (LE) is regarded as the gold standard for RVMI assessment. We aimed
      to determine the impact of initial angiographic status and salutary effect of
      primary percutaneous coronary intervention (PCI) on the presence of RVMI. In 114
      patients undergoing emergency angiography and primary PCI of right coronary
      artery, 3-5 days after index PCI, LE CMRI was performed for assessing the RVMI.
      Forty-eight patients (42%) demonstrated RVMI. Multivariate regression analysis
      identified TIMI flow <2 in at least one RV branch after PCI as an independent
      angiographic predictor of RVMI [odds ratio (OR) 143.00, 95% confidence interval
      (CI) 18.10-1130.05, p < 0.001]. ST-segment elevation >= 1 mm in V4R was present
      in 83 (73%). TIMI flow <3 in at least one RV branch before PCI (OR 4.07, 95% CI
      1.24-13.33, p = 0.02) was independent angiographic predictor of ST-segment
      elevation >= 1 mm in V4R. The only predictor of RVMI was TIMI flow <2 in at least
      one RV branch after PCI. ST-segment elevation >= 1 mm in V4R is caused by TIMI <3
      flow in at least one RV branch before index PCI.

PMID- 26208684
TI  - Preoperative evaluation for coronary atherosclerosis with computed tomography
      angiography in intravenous drug users: an emerging indication in the face of a
      growing threat.
AB  - The purpose of this study was to describe the application of coronary computed
      tomography angiography (CCTA) in evaluation of patients with history of
      intravenous drug use (IDU). An IRB approved retrospective review was performed of
      all patients who had a prior history of IDU and presenting with endocarditis who
      had undergone CCTA. Demographic characteristics and cardiovascular risk factors
      were collected. In addition, we reviewed CCTA reports for dosimetric parameters,
      calcium score, and atherosclerotic burden. There were 32 patients (25 males)
      included in this study with a mean age of 38 +/- 10.8 years. The average BMI for
      the study group was 26.5 +/- 4.9. 44 % of patients had evidence of
      atherosclerotic disease on coronary CTA. Mean calcium score was 175 +/- 487.
      Median total exam effective dose was 4.8 mSv (range: 3.3-7.3 mSv). In spite of
      their relatively young age and BMI at the upper limits of normal, patients with
      history of IDU have atherosclerosis and coronary CTA can be utilized to screen
      these patients and may be helpful for risk stratification prior to noncoronary
      surgical procedures. Given the recent rise in IDU, this may become a growing
      indication for CCTA.

PMID- 26208685
TI  - Comparison of long-term in-stent vascular response between abluminal groove
      filled biodegradable polymer sirolimus-eluting stent and durable polymer
      everolimus-eluting stent: 3-year OCT follow-up from the TARGET I trial.
AB  - The study sought to compare long-term optical coherence tomography (OCT)-based in
      stent vascular response between the abluminal groove-filled biodegradable polymer
      sirolimus-eluting stent (SES) and the durable polymer everolimus-eluting stent
      (EES) in the TARGET I trial. The TARGET I trial was a prospective, multicenter,
      randomized clinical trial which enrolled 458 patients with single de novo lesions
      treated by abluminal groove-filled biodegradable polymer SES and EES. A subset of
      43 patients underwent angiography and OCT examinations at 3 years. All OCT images
      were analyzed at 0.4 mm intervals. A similar increase in angiographic late lumen
      loss was observed in SES and EES (from 0.05 +/- 0.05 vs. 0.05 +/- 0.05 mm [p =
      0.84] at 9 months to 0.25 +/- 0.37 vs. 0.26 +/- 0.19 mm [p = 0.99] at 3 years,
      respectively), without significant differences at 3 years in mean neointimal
      thickness of stent struts (SES: 0.13 +/- 0.02 mm vs. EES: 0.13 +/- 0.02 mm, p =
      0.80); mean percentage of covered struts (SES: 99.2 % vs. EES: 99.3 %, p = 0.53),
      or malapposed strut rates (SES: 0.08 % vs. EES: 0.06 %, p = 0.15). The OCT-based
      in-stent vascular response evaluation found similar vascular healing for the two
      studied devices, indicating that the luminal loss in EES from 9 months to 3 years
      cannot be imputed on its coated biocompatible polymer.

PMID- 26208686
TI  - Experimental colitis and malnutrition differentially affect the metabolism of
      glutathione and related sulfhydryl metabolites in different tissues.
AB  - PURPOSE: Inflammatory bowel diseases (IBD) are characterized by severe
      inflammation within the gastrointestinal (GI) tract. This inflammation is known
      to drive the catabolism of protein in the affected tissue and modulate systemic
      protein metabolism. Yet despite the established increase in oxidative stress and
      changes in protein catabolism, little is known as to the effects of IBD on
      metabolism of glutathione (GSH) and related metabolites. The aim of this study
      was to conduct a comprehensive analysis of the response of GSH and related
      sulfhydryl metabolites to malnutrition and GI inflammation. We hypothesized that
      the inflammatory stress of colitis would decrease the concentration and the
      synthesis of GSH in various tissues of well-nourished piglets. Additionally, the
      superimposition of malnutrition on colitis would further decrease glutathione
      status. METHODS: Healthy, well-nourished piglets were compared to those receiving
      dextran sulphate sodium-induced, a macronutrient-restricted diet or both. The
      synthesis of GSH was determined by primed constant infusion of
      [(15)N,(13)C2]glycine and tandem mass spectrometry analysis. Additionally, the
      concentrations of GSH and related sulfhydryl metabolites were also determined by
      UHPLC-tandem mass spectrometry-a novel analytic technique. RESULTS: In healthy
      piglets, GSH synthesis was highest in the liver, along with the concentrations of
      both cysteine and gamma-glutamylcysteine. Piglets with colitis had decreased
      synthesis of GSH and decreased concentrations of GSH, cysteine and gamma
      glutamylcysteine in the distal colon compared to healthy controls. Additionally,
      there was no change with superimposition of malnutrition on colitis in the distal
      colon. CONCLUSION: Synthesis and metabolism of GSH are uniquely regulated in each
      tissue. Colitis, independent of nutrition, compromises GSH status and the
      concentration of cysteine in the distal colon of piglets with GI inflammation.
      The techniques developed in this study have translational applications and can be
      scaled for use in clinical investigation of GI inflammation.

PMID- 26208688
TI  - A Single-Step Purification of Cauliflower Lysozyme and Its Dual Role Against
      Bacterial and Fungal Plant Pathogens.
AB  - A novel lysozyme from cauliflower was purified in a single step, for the first
      time, using Sephadex G100 column chromatography. The purified lysozyme exhibited
      a homogenized single band in sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE), and its molecular mass was calculated to be 22.0 kDa.
      The purified lysozyme showed activity between 30 to 60  degrees C with 40 
      degrees C as the optimum temperature for its maximal activity. Although the
      purified lysozyme was functional at pH ranges between 3.0 and 9.0, the optimum pH
      for the enzyme activity was 8.0. By Michaelis-Menten equation, the threshold
      substrate concentration for the optimal enzyme activity was calculated to be
      133.0 MUg. The purified lysozyme showed extraordinary activity against plant
      pathogenic bacteria and fungi. At 10-MUg concentrations, it inhibited the growth
      of plant pathogenic bacteria such as Pseudomonas syringae, Xanthomonas
      campestris, and Erwinia carotovora exhibiting 4.28, 5.90, and 3.88-fold
      inhibition, respectively. Further, it also completely inhibited the conidial
      germination of Archemonium obclavatum and, to a very large extent, other fungal
      species such as Fusarium solani (79.3 %), Leptosphaeria maculans (88.6 %),
      Botrytis cinera (73.3 %), Curvularia lunata (68 %), Rhizoctonia solani (79.6 %),
      and Alternaria alternata (83.6 %).

PMID- 26208687
TI  - Maternal zinc supplementation improves hepatitis B antibody responses in infants
      but decreases plasma zinc level.
AB  - PURPOSE: The World Health Report identifies zinc deficiency as one of the major
      causes of disease in developing countries, and infants are at particular risk. We
      aimed to investigate the effect of maternal zinc supplementation on the infant's
      immune function in a population at risk of deficiency. METHODS: In a randomized,
      double-blind placebo-controlled trial, mothers were supplemented either with 20
      mg/day of elemental zinc (n = 20) or placebo (n = 19) at the beginning of second
      trimester, which continued until 6 months postpartum. Indicators of the infants'
      immune function measured included interleukin (IL)-7, thymic size and response to
      hepatitis B vaccination. RESULTS: Infants born from mothers receiving zinc
      supplements during pregnancy and postpartum had significantly lower plasma zinc
      (p < 0.05) but marginally higher IL-7 and antibody responses to hepatitis B
      vaccination (p < 0.10) than infants born from mothers not receiving zinc.
      Maternal zinc supplementation showed no negative impact on copper status of
      mothers or their infants. Maternal zinc supplementation did not influence infant
      thymic size, but cord blood IL-7 was found positively associated with thymus size
      at 1 month of age (r = 0.392) and with hepatitis B vaccine response at 6 months
      of age (r = 0.386). CONCLUSION: Prenatal and postnatal zinc supplementation
      marginally improved T cell-dependent antibody responses in infants along with IL
      7, a cytokine involved in human T cell development and maintaining homeostasis.

PMID- 26208689
TI  - Somatic Embryogenesis and Plant Regeneration in Sapindus mukorossi Gaertn. from
      Leaf-Derived Callus Induced with 6-Benzylaminopurine.
AB  - A somatic embryogenesis system was developed for Sapindus mukorossi Gaertn. from
      leaf explants obtained from fresh flushes of a mature tree. Callus was induced
      from the midrib region of leaf explants on Murashige and Skoog (MS) medium
      containing different concentrations of 2,4-dichlorophenoxyacetic acid or 6
      benzylaminopurine. Callus induction and somatic embryogenesis was significantly
      influenced by the size, physiological age, and orientation of leaf explants on
      the culture medium and plant growth regulators. Adaxial-side-up orientation of
      leaf explants significantly promoted embryogenesis in comparison with abaxial
      side-up orientation. Maximum number of somatic embryos was induced on MS medium
      supplemented with 8.88 MUM 6-benzylaminopurine. Scanning electron microscopy of
      embryogenic callus revealed somatic embryo origin and the development of globular
      , heart-, and cotyledonary-stage somatic embryos. The frequency of maturation as
      well as germination of somatic embryos was higher on MS medium containing 8.88
      MUM 6-benzylaminopurine than on medium without 6-benzylaminopurine. Plantlets
      which developed from somatic embryos were acclimatized successfully with 90 %
      survival.

PMID- 26208690
TI  - Investigation of Nalidixic Acid Resistance Mechanism in Salmonella enterica Using
      Molecular Simulation Techniques.
AB  - The emergence of nalidixic acid-resistant strains of Salmonella typhimurium
      remains to be a major public health problem. In particular, the substitution of
      Asn in place of Asp at the 87 loci in the GyrA of S. typhimurium was
      experimentally stated for nalidixic acid resistance. However, the data on the
      possible mechanism of nalidixic acid resistance are limited. In this study, I
      Mutant2.0 and DUET program were employed to explore the impact of mutation on the
      stability of GyrA protein. Subsequently, molecular simulation techniques were
      employed to provide detailed information on the nalidixic acid-resistant
      associates with the D87N mutation in the GyrA of S. typhimurium. The binding free
      energy data depicts that nalidixic acid forms stable complex only with native
      type GyrA than mutant (D87N) type GyrA protein. Moreover, our results
      theoretically suggest that hydrogen bonding formed by the Arg91 is certainly
      responsible for the GyrA of S. typhimurium drug selectivity. It is hoped that
      these evidences are immensely important for the development of new antibiotic and
      to overcome the nalidixic acid resistance in the near future.

PMID- 26208691
TI  - Caspases and Thrombin Activity Regulation by Specific Serpin Inhibitors in Bovine
      Skeletal Muscle.
AB  - In living cells, after activation, protein inhibitors constitute the last step of
      proteases activity regulation. This review intends to provide original
      information about a group of bovine muscle serine proteases inhibitors belonging
      to the Serpin superfamily and characterized at the gene and protein level. This
      report is the only one and the first to provide much information on this group of
      proteases inhibitors of the serpin type and their potential biological functions.
      Amongst the eight genes identified in bovine, three serpins were purified from
      the muscle tissue and characterized. These are two members of the bovSERPINA3
      family, i.e., bovSERPINA3-1 and A3-3, and the last one is antithrombin III (AT
      III or BovSERPINC1). BovSERPINA3 family comprises at least eight protein members
      encoded by different genes mapped on chromosome 7q23-q26 cluster. BovSERPINA3-1
      and A3-3 were shown to locate within muscle cells and are cross-class inhibitors
      strongly active against trypsin as well as against human initiator and effector
      caspases 8 and 3. They constitute a key apoptosis control in mammals. They were
      thus expressed in proliferating and confluent myoblasts phases where cells must
      be alive but not in myotubes. Antithrombin III inhibits trypsin and, in a heparin
      dependent manner, thrombin. AT-III and its mRNA were expressed in muscle cells
      and in differentiating primary myoblasts in culture. 

PMID- 26208692
TI  - Regulating Pyruvate Carboxylase in the Living Culture of Aspergillus Terreus Nrrl
      1960 by L-Aspartate for Enhanced Itaconic Acid Production.
AB  - Aspergillus terreus was reported as the promising fungal strain for itaconic
      acid; however, the commercial production suffers from the low yield. Low
      production yield was claimed as the result of completing the tricarboxylic acid
      (TCA) cycle towards biomass synthesis while under limiting phosphate and
      nitrogen; TCA cycle was somewhat shunted and consequently, the metabolite fluxes
      move towards itaconic acid production route. By regulating enzymes in TCA cycle,
      it is believed that itaconic acid production can be improved. One of the key
      responsible enzymes involved in itaconic acid production was triggered in this
      study. Pyruvate carboxylase was allosterically inhibited by L-aspartate. The
      presence of 10 mM L-aspartate in the production medium directly repressed PC
      expression in the living A. terreus while the limited malate flux regulated the
      malate/citrate antiporters resulting in the increasing cis-aconitate
      decarboxylase activity to simultaneously convert cis-aconitate, citrate isomer,
      into itaconic acid. The transport of cis-aconitate via the antiporters induced
      citrate synthase and 6-phosphofructo-1-kinase activities in response to balance
      the fluxes of TCA intermediates. Successively, itaconic acid production yield and
      final concentration could be improved by 8.33 and 60.32 %, respectively, compared
      to those obtained from the control fermentation with the shortened lag time to
      produce itaconic acid during the production phase.

PMID- 26208693
TI  - Integrating the Electronic Health Record into Behavioral Health Encounters:
      Strategies, Barriers, and Implications for Practice.
AB  - Despite increasing rates of electronic health record (EHR) adoption, the impact
      of these systems on the delivery of behavioral health treatment remains poorly
      understood. This qualitative study examined the experiences of 37 behavioral
      health providers using EHRs during face-to-face visits. Providers described
      environmental, relational and system related strategies that were used to
      meaningfully integrate EHRs into treatment and enhance the patient-centeredness
      of clinical encounters. Barriers to deploying these techniques were also
      identified. Results contribute to limited research exploring EHR use in
      behavioral health care, and provide important insight into how systems can be
      optimized within this context.

PMID- 26208696
TI  - Nursing futility, managing medicine: Nurses' perspectives on the transition from
      life-prolonging to palliative care.
AB  - The shift from life-prolonging and palliative care can be fraught with
      interpersonal complexities as patients face dilemmas around mortality and the
      dying process. Nurses can play a central role in managing these moments, often
      with a focus on promoting and enhancing communication around: the meaning of
      palliative care, the nature of futility and the dying process more broadly. These
      sites of nurse-patient communication can be highly charged and pose unique
      challenges to nurses including how to balance nursing perspectives versus those
      of other stakeholders including doctors. Here, drawing on interviews with nurses,
      we explore their accounts of communication about futility and the process of
      transitioning to palliative care. The interviews reveal nurses' perspectives on
      the following: the art of conversing around futility and managing patient
      resistance, the influence of guilt and individual biographies in shaping
      communication, the importance of non-verbal and the informal in communication,
      the impact of conflicting organisational expectations on nurses and the process
      of learning to effectively communicate. We argue that these transitional moments
      articulate important, and at times problematic, aspects of contemporary nursing
      and nurse-medical relations.

PMID- 26208694
TI  - Listening to Our Gut: Contribution of Gut Microbiota and Cardiovascular Risk in
      Diabetes Pathogenesis.
AB  - What we understand about diabetes from decades of genetics research is now being
      supplemented with exciting new evidence based on a better understanding of how
      one of the biggest "environmental" factors the body is exposed to is influencing
      the pathogenesis of disease. The recent discovery that certain dietary nutrients
      possessing a trimethylamine (TMA) moiety (namely choline/phosphatidylcholine and
      L-carnitine) participate in the development of atherosclerotic heart disease has
      renewed attention towards the contributions of gut microbiota in the development
      of cardiovascular diseases. Collectively, animal and human studies reveal that
      conversion of these nutrient precursors to trimethylamine N-oxide (TMAO) depends
      on both microbial composition and host factors, and can be induced by dietary
      exposures. In addition, circulating TMAO levels are strongly linked to
      cardiovascular disease risks and various adverse cardio-renal consequences. Our
      group and others have further demonstrated that circulating TMAO levels are
      elevated in patients with type 2 diabetes mellitus compared to healthy controls
      and gut microbiota-dependent phosphatidylcholine metabolism has been implicated
      in metabolic dysregulation and insulin resistance in animal models. Therefore,
      preventive strategies to minimize adverse consequences associated with TMAO
      generation in the diabetic population are warranted. 

PMID- 26208695
TI  - Emergence of hepatitis C virus NS5A L31V plus Y93H variant upon treatment failure
      of daclatasvir and asunaprevir is relatively resistant to ledipasvir and NS5B
      polymerase nucleotide inhibitor GS-558093 in human hepatocyte chimeric mice.
AB  - BACKGROUND: Resistance-associated variants (RAVs) emerge at multiple positions
      spanning hepatitis C virus (HCV) NS3/4A and NS5A regions upon failure of
      asunaprevir/daclatasvir combination therapy. It has not been determined whether
      the emergence of such RAVs have an impact on re-treatment by a combination of
      ledipasvir and sofosbuvir, a potent regimen for HCV genotype 1 infection.
      METHODS: TK-NOG human hepatocyte chimeric mice were inoculated with sera from a
      patient with treatment failure of asunaprevir/daclatasvir therapy. RESULTS: They
      developed persistent HCV infection with triple variants of NS3/4A D168V, NS5A
      L31V plus Y93H. Administration of ledipasvir/GS-558093 (a NS5B nucleotide analog)
      in these mice failed to achieve end-of-treatment response or sustained virologic
      response, which was in sharp contrast to the results in mice with wild-type virus
      infection. The administration of telaprevir/GS-558093 successfully achieved it in
      those mice. CONCLUSIONS: Treatment failure with asunaprevir/daclatasvir may limit
      further treatment options. This population may represent a growing unmet medical
      need.

PMID- 26208697
TI  - Resignifying the sickle cell gene: Narratives of genetic risk, impairment and
      repair.
AB  - Connecting theoretical discussion with empirical qualitative work, this article
      examines how sickle cell became a site of public health intervention in terms of
      'racialised' risks. Historically, sickle cell became socio-politically allied to
      ideas of repair, in terms of the state improving the health of a neglected ethnic
      minority population. Yet, we elucidate how partial improvements in care and
      education arose alongside preventative public health screening efforts. Using
      qualitative research based in the United Kingdom, we show how a focus on
      collective efforts of repair can lie in tension with how services and individuals
      understand and negotiate antenatal screening. We illustrate how screening for
      sickle cell disorder calls into question narrative identity, undoing paradigms in
      which ethnicity, disablement and genetic impairment become framed. Research
      participants noted that rather than 'choices', it is 'risks' and their
      negotiation that are a part of discourses of modernity and the new genetics.
      Furthermore, while biomedical paradigms are rationally and ethically
      (de)constructed by participants, this was never fully engaged with by
      professionals, contributing to overall perception of antenatal screening as
      disempowering and leading to disengagement.

PMID- 26208698
TI  - Withania somnifera Suppresses Tumor Growth of Intracranial Allograft of Glioma
      Cells.
AB  - Gliomas are the most frequent type of primary brain tumor in adults. Their highly
      proliferative nature, complex cellular composition, and ability to escape
      therapies have confronted investigators for years, hindering the advancement
      toward an effective treatment. Agents that are safe and can be administered as
      dietary supplements have always remained priority to be most feasible for cancer
      therapy. Withania somnifera (ashwagandha) is an essential ingredient of Ayurvedic
      preparations and is known to eliminate cancer cells derived from a variety of
      peripheral tissues. Although our previous studies have addressed the in vitro
      anti-proliferative and differentiation-inducing properties of ashwagandha on
      neuronal cell lines, in vivo studies validating the same are lacking. While
      exploring the mechanism of its action in vitro, we observed that the ashwagandha
      water extract (ASH-WEX) induced the G2/M phase blockade and caused the activation
      of multiple pro-apoptotic pathways, leading to suppression of cyclin D1, bcl-xl,
      and p-Akt, and reduced the expression of polysialylated form of neural cell
      adhesion molecule (PSA-NCAM) as well as the activity of matrix
      metalloproteinases. ASH-WEX reduced the intracranial tumor volumes in vivo and
      suppressed the tumor-promoting proteins p-nuclear factor kappa B (NF-kappaB), p
      Akt, vascular endothelial growth factor (VEGF), heat shock protein 70 (HSP70),
      PSA-NCAM, and cyclin D1 in the rat model of orthotopic glioma allograft.
      Reduction in glial fibrillary acidic protein (GFAP) and upregulation of mortalin
      and neural cell adhesion molecule (NCAM) expression specifically in tumor-bearing
      tissue further indicated the anti-glioma efficacy of ASH-WEX in vivo. Combining
      this enhanced understanding of the molecular mechanisms of ASH-WEX in glioma with
      in vivo model system offers new opportunities to develop therapeutic strategy for
      safe, specific, and effective formulations for treating brain tumors.

PMID- 26208699
TI  - Hydrogen Sulfide Prevents Synaptic Plasticity from VD-Induced Damage via Akt/GSK
      3beta Pathway and Notch Signaling Pathway in Rats.
AB  - Our previous study has demonstrated that hydrogen sulfide (H2S) attenuates
      neuronal injury induced by vascular dementia (VD) in rats, but the mechanism is
      still poorly understood. In this study, we aimed to investigate whether the
      neuroprotection of H2S was associated with synaptic plasticity and try to
      interpret the potential underlying mechanisms. Adult male Wistar rats were
      suffered the ligation of bilateral common carotid arteries. At 24 h after
      surgery, rats were administered intraperitoneally with sodium hydrosulfide (NaHS,
      5.6 mg.kg(-1).day(-1)), a H2S donor, for 3 weeks in the VD+NaHS group and treated
      intraperitoneally with saline in the VD group respectively. Our results
      demonstrated that NaHS significantly decreased the level of glutamate. It
      obviously ameliorated cognitive flexibility as well as the spatial learning and
      memory abilities by Morris water maze. Moreover, NaHS significantly improved the
      long-term depression (LTD), and was able to elevate the expression of N-methyl-D
      aspartate receptor subunit 2A, which plays a pivotal role in synaptic plasticity.
      Interestingly, NaHS decreased the phosphorylation of Akt, and it could maintain
      the activity of glycogen synthase kinase-3beta (GSK-3beta). Surprisingly, NaHS
      triggered the canonical Notch pathway by increasing expressions of Jagged-1 and
      Hes-1. These findings suggest that NaHS prevents synaptic plasticity from VD
      induced damage partly via Akt/GSK-3beta pathway and Notch signaling
      pathway.Hydrogen sulfide modulated the ratio of NMDAR 2A/2B and improved the
      synaptic plasticity via Akt/GSK-3beta pathway and Notch signaling pathway in VD
      rats.

PMID- 26208700
TI  - Nuclear Factor-kappaB-Dependent Sestrin2 Induction Mediates the Antioxidant
      Effects of BDNF Against Mitochondrial Inhibition in Rat Cortical Neurons.
AB  - Brain-derived neurotrophic factor (BDNF), in addition to its neurotrophic action,
      also possesses antioxidant activities. However, the underlying mechanisms remain
      to be fully defined. Sestrin2 is a stress-responsive gene implicated in the
      cellular defense against oxidative stress. Currently, the potential functions of
      sestrin2 in nervous system, in particular its correlation with neurotrophic
      factors, have not been well established. In this study, we hypothesized that BDNF
      may enhance sestrin2 expression to confer neuronal resistance against oxidative
      stress induced by 3-nitropropionic acid (3-NP), an irreversible mitochondrial
      complex II inhibitor, and characterized the molecular mechanisms underlying BDNF
      induction of sestrin2 in primary rat cortical cultures. We found that BDNF
      mediated sestrin2 expression in cortical neurons required formation of nitric
      oxide (NO) with subsequent production of 3',5'-cyclic guanosine monophosphate
      (cGMP) and activation of cGMP-dependent protein kinase (PKG). BDNF induced
      localization of nuclear factor-kappaB (NF-kappaB) subunits p65 and p50 into
      neuronal nuclei that required PKG activities. Interestingly, BDNF exposure led to
      formation of a protein complex containing at least PKG-1 and p65/p50, which bound
      to sestrin2 promoter with resultant upregulation of its protein products.
      Finally, BDNF preconditioning mitigated production of reactive oxygen species
      (ROS) as a result of 3-NP exposure; this antioxidative effect of BDNF was
      dependent upon PKG activity, NF-kappaB, and sestrin2. Taken together, our results
      indicated that BDNF enhances sestrin2 expression to confer neuronal resistance
      against oxidative stress induced by 3-NP through attenuation of ROS formation;
      furthermore, BDNF induction of sestrin2 requires activation of a pathway
      involving NO/PKG/NF-kappaB.

PMID- 26208701
TI  - Astrocytic CCAAT/Enhancer Binding Protein delta Regulates Neuronal Viability and
      Spatial Learning Ability via miR-135a.
AB  - The progression of Alzheimer's disease (AD) has been associated with astrocytes
      induced neuroinflammation. However, the detailed mechanism of astrocytes
      associated with learning impairments and neuronal loss in AD is poorly defined.
      Here, we provide novel evidences that astrocytic miR-135a is critical for
      neuronal viability and spatial learning ability in vivo. The AppTg/Cebpd (-/-)
      mice showed a spatial learning improvement compared with the APPswe/PS1/E9
      bigenic (AppTg) mice. miR-135a was found to be a CCAAT/enhancer binding protein
      delta (CEBPD) responsive miRNA and can repress the transcription of
      thrombospondin 1 (THBS1) / Thbs1 (mouse) via its 3'-untranslated region (3'UTR).
      We used different experimental approaches to attenuate the expression of
      CEBPD/Cebpd (mouse) or miR-135a in astrocytes and found the following results:
      increase in THBS1/Thbs1 expression, decrease in neuronal apoptosis, and increase
      in growth of neurites. Importantly, injection of miR-135a antagonist (AM135a)
      into the brain of AppTg mice was found to prevent neuronal apoptosis and improved
      the spatial learning ability. Together, our findings demonstrate a critical
      function for the astrocytic CEBPD, and point to miR-135a antagonist as an
      attractive therapeutic target for the treatment of Alzheimer's disease.

PMID- 26208702
TI  - Role of nitric oxide in immune responses against viruses: beyond microbicidal
      activity.
AB  - INTRODUCTION: Nitric oxide (NO) is a free radical produced during L-arginine
      metabolism. In addition to its physiological activities in vascular and neuronal
      functions, its role in the immune system as a microbicide and tumor-killing
      mediator has been well described, as well as its release by activated
      macrophages. Furthermore, NO is produced by a variety of immune and non-immune
      cells and is involved in the regulation of several immune functions, such as T
      cell polarization and suppression. RESULTS: Viral infections generally promote NO
      production; however, according to its concentration, NO can trigger different
      effector mechanisms in immune responses. NO can activate the second messenger
      cyclic guanosine monophosphate (cGMP), can increase the cytoplasmic p53 tumor
      suppressor molecule, and can modify host and viral molecules by nitrosylation.
      Because of its microbicide function, NO has frequently been considered a
      protective mediator in viral infections; however, in some cases NO could be
      deleterious, potentiating inflammation or contributing to virus latency.
      CONCLUSIONS: Thus, advances in the knowledge of the role of NO in
      immunomodulation and in the pathogenesis of viral diseases could contribute not
      only to the development of vaccines and therapeutic strategies but also to the
      use of its metabolites (nitrate/nitrite) and the enzyme responsible for its
      production (iNOS) as prognostic markers of some of these viral infections.

PMID- 26208703
TI  - Processing of Positive and Negative Feedback in Patients with Cerebellar Lesions.
AB  - It is well accepted that the cerebellum plays a crucial role in the prediction of
      the sensory consequences of movements. Recent findings of altered error
      processing in patients with selective cerebellar lesions led to the hypothesis
      that feedback processing and feedback-based learning might be affected by
      cerebellar damage as well. Thus, the present study investigated learning from and
      processing of positive and negative feedback in 12 patients with selective
      cerebellar lesions and healthy control subjects. Participants performed a
      monetary feedback learning task. The processing of positive and negative feedback
      was assessed by means of event-related potentials (ERPs) during the learning task
      and during a separate task in which the frequencies of positive and negative
      feedback were balanced. Patients did not show a general learning deficit compared
      to controls. Relative to the control group, however, patients with cerebellar
      lesions showed significantly higher ERP difference wave amplitudes (rewards
      losses) in a time window between 250 and 450 ms after feedback presentation,
      possibly indicating impaired outcome prediction. The analysis of the original
      waveforms suggested that patients and controls primarily differed in their
      pattern of feedback-related negativity and P300 amplitudes. Our results add to
      recent findings on altered performance monitoring associated with cerebellar
      damage and demonstrate, for the first time, alterations of feedback processing in
      patients with cerebellar damage. Unaffected learning performance appears to
      suggest that chronic cerebellar lesions can be compensated in behaviour. 

PMID- 26208704
TI  - Dysplastic Cerebellar Epilepsy: Complete Seizure Control Following Resection of a
      Ganglioglioma.
AB  - Subcortical epilepsy has been a controversial issue, partially settled by
      evidence showing seizure generation in hypothalamic hamartomas and also by
      reports of seizures caused by cerebellar lesions. We report 4-year-old girl with
      right hemifacial seizures and autonomic phenomena, in whom MRI showed an
      irregular mass in the right cerebellar peduncle. Despite several unremarkable
      video-EEG recordings, seizure origin in the lesion was hypothesized. Complete
      resection was feasible, histopathology showed a ganglioglioma, and she has been
      seizure free for 3 years. A fine line separates these developmental tumors from
      focal cortical dysplasia, and the homogeneous presentation of this entity led us
      to propose the terminology dysplastic cerebellar epilepsy. 

PMID- 26208705
TI  - Contribution of the Cerebellum in Cue-Dependent Force Changes During an Isometric
      Precision Grip Task.
AB  - The "raspberry task" represents a precision grip task that requires continuous
      adjustment of grip forces and pull forces. During this task, subjects use a
      specialised grip rod and have to increase the pull force linearly while the rod
      is locked. The positions of the fingers are unrestrained and freely selectable.
      From the finger positions and the geometry of the grip rod, a physical lever was
      derived which is a comprehensive measurement of the subject's grip behaviour. In
      this study, the involvement of the cerebellum in establishing cued force changes
      (CFC) was examined. The auditory stimulus was associated with a motor behaviour
      that has to be readjusted during an ongoing movement that already started.
      Moreover, cerebellar involvement on grip behaviour was examined. The results show
      that patients presenting with degenerating cerebellar disease (CBL) were able to
      elicit CFC and were additionally able to optimise grip behaviour by minimising
      the lever. Comparison of the results of CBL with a control group of healthy
      subjects showed, however, that the CFC incidence was significantly lower and the
      reduction of the lever was less in CBL. Hence, the cerebellum is involved not
      only in the classical conditioning of reflexes but also in the association of
      sensory stimuli with complex changes in motor behaviour. Furthermore, the
      cerebellum is involved in the optimisation of grip behaviour during ongoing
      movements. Recent studies lead to the assumption that the cerebello-reticulo
      spinal pathway might be important for the reduced optimisation of grip behaviour
      in CBL. 

PMID- 26208707
TI  - Tools to investigate how interprofessional education activities link to
      competencies.
AB  - Integrating interprofessional education (IPE) activities and curricular
      components in health professions education has been emphasized recently by the
      inclusion of accreditation standards across disciplines. The Interprofessional
      Education Collaborative (IPEC) established IPE competencies in 2009, but
      evaluating how activities link to competencies has not been investigated in
      depth. The purpose of this project is to investigate how well two IPE activities
      align with IPEC competencies. To evaluate how our IPE activities met IPEC
      competencies, we developed a checklist and an observation instrument. A brief
      description of each is included as well as the outcomes. We analyzed Disaster
      Day, a simulation exercise that includes participants from Nursing, Medicine, and
      Pharmacy, and Interprofessional Healthcare Ethics (IPHCE), a course that
      introduced medical, nursing, and pharmacy students to ethical issues using
      didactic sessions and case discussions. While both activities appeared to
      facilitate the development of IPE competencies, Disaster Day aligned more with
      IPEC competencies than the IPHCE course and appears to be a more comprehensive
      way of addressing IPEC competencies. However, offering one IPE activity or
      curricular element is not sufficient. Having several IPE options available,
      utilizing the tools we developed to map the IPE curriculum and evaluating
      competency coverage is recommended. 

PMID- 26208706
TI  - Stress and burnout among critical care fellows: preliminary evaluation of an
      educational intervention.
AB  - BACKGROUND: Despite a demanding work environment, information on stress and
      burnout of critical care fellows is limited. OBJECTIVES: To assess 1) levels of
      burnout, perceived stress, and quality of life in critical care fellows, and 2)
      the impact of a brief stress management training on these outcomes. METHODS: In a
      tertiary care academic medical center, 58 critical care fellows of varying
      subspecialties and training levels were surveyed to assess baseline levels of
      stress and burnout. Twenty-one of the 58 critical care fellows who were in the
      first year of training at the time of this initial survey participated in a pre
      test and 1-year post-test to determine the effects of a brief, 90-min stress
      management intervention. RESULTS: Based on responses (n=58) to the abbreviated
      Maslach Burnout Inventory, reported burnout was significantly lower in Asian
      fellows (p=0.04) and substantially higher among graduating fellows (versus new
      and transitioning fellows) (p=0.02). Among the intervention cohort, burnout did
      not significantly improve--though two-thirds of fellows reported using the
      interventional techniques to deal with stressful situations. Fellows who
      participated in the intervention rated the effectiveness of the course as 4
      (IQR=3.75-5) using the 5-point Likert scale. CONCLUSIONS: In comparison with the
      new and transitioning trainees, burnout was highest among graduating critical
      care fellows. Although no significant improvements were found in first-year
      fellows' burnout scores following the single, 90-min training intervention,
      participants felt the training did provide them with tools to apply during
      stressful situations.

PMID- 26208708
TI  - Longitudinal evaluation of aflatoxin exposure in two cohorts in south-western
      Uganda.
AB  - Aflatoxins (AF) are a group of mycotoxins. AF exposure causes acute and chronic
      adverse health effects such as aflatoxicosis and hepatocellular carcinoma in
      human populations, especially in the developing world. In this study, AF exposure
      was evaluated using archived serum samples from human immunodeficiency virus
      (HIV)-seronegative participants from two cohort studies in south-western Uganda.
      AFB1-lysine (AFB-Lys) adduct levels were determined via HPLC fluorescence in a
      total of 713 serum samples from the General Population Cohort (GPC), covering
      eight time periods between 1989 and 2010. Overall, 90% (642/713) of the samples
      were positive for AFB-Lys and the median level was 1.58 pg mg(-1) albumin (range
      = 0.40-168 pg mg(-1) albumin). AFB-Lys adduct levels were also measured in a
      total of 374 serum samples from the Rakai Community Cohort Study (RCCS), across
      four time periods between 1999 and 2003. The averaged detection rate was 92.5%
      (346/374) and the median level was 1.18 pg mg(-1) albumin (range = 0.40-122.5 pg
      mg(-1) albumin). In the GPC study there were no statistically significant
      differences between demographic parameters, such as age, sex and level of
      education, and levels of serum AFB-Lys adduct. In the RCCS study, longitudinal
      analysis using generalised estimating equations revealed significant differences
      between the adduct levels and residential areas (p = 0.05) and occupations (p =
      0.02). This study indicates that AF exposure in people in two populations in
      south-western Uganda is persistent and has not significantly changed over time.
      Data from one study, but not the other, indicated that agriculture workers and
      rural area residents had more AF exposure than those non-agricultural workers and
      non-rural area residents. These results suggest the need for further study of AF
      induced human adverse health effects, especially the predominant diseases in the
      region. 

PMID- 26208710
TI  - Margaret McCartney: The "breakthrough" drug that's not been shown to help in
      Alzheimer's disease.

PMID- 26208709
TI  - Movement sequencing in normal aging: speech, oro-facial, and finger movements.
AB  - The manner and extent to which normal aging affects the ability to speak are not
      fully understood. While age-related changes in voice fundamental frequency and
      intensity have been documented, changes affecting the planning and articulation
      of speech are less well understood. In the present study, 76 healthy, cognitively
      normal participants aged between 18 and 93 years old were asked to produce
      auditorily and visually triggered sequences of finely controlled movements
      (speech, oro-facial, and manual movement). These sequences of movements were
      either (1) simple, in which at least two of the three movements were the same, or
      (2) complex, in which three different movements were produced. For each of the
      resulting experimental condition, accuracy was calculated. The results show that,
      for speech and oro-facial movements, accuracy declined as a function of age and
      complexity. For these movements, the negative effect of complexity on performance
      accuracy increased with age. No aging or complexity effects were found for the
      manual movements on accuracy, but a significant slowing of movement was found,
      particularly for the complex sequences. These results demonstrate that there is a
      significant deterioration of fine motor control in normal aging across different
      response modalities.

PMID- 26208711
TI  - Housing and sexual health among street-involved youth.
AB  - Street-involved youth (SIY) carry a disproportionate burden of sexually
      transmitted diseases (STD). Studies among adults suggest that improving housing
      stability may be an effective primary prevention strategy for improving sexual
      health. Housing options available to SIY offer varying degrees of stability and
      adult supervision. This study investigated whether housing options offering more
      stability and adult supervision are associated with fewer STD and related risk
      behaviors among SIY. A cross-sectional study was performed using public health
      survey and laboratory data collected from Toronto SIY in 2010. Three exposure
      categories were defined a priori based on housing situation: (1) stable and
      supervised housing, (2) stable and unsupervised housing, and (3) unstable and
      unsupervised housing. Multivariate logistic regression was used to test the
      association between housing category and current or recent STD. Secondary
      analyses were performed using the following secondary outcomes: blood-borne
      infection, recent binge-drinking, and recent high-risk sexual behavior. The final
      analysis included 184 SIY. Of these, 28.8 % had a current or recent STD. Housing
      situation was stable and supervised for 12.5 %, stable and unsupervised for 46.2
      %, and unstable and unsupervised for 41.3 %. Compared to stable and supervised
      housing, there was no significant association between current or recent STD among
      stable and unsupervised housing or unstable and unsupervised housing. There was
      no significant association between housing category and risk of blood-borne
      infection, binge-drinking, or high-risk sexual behavior. Although we did not
      demonstrate a significant association between stable and supervised housing and
      lower STD risk, our incorporation of both housing stability and adult supervision
      into a priori defined exposure groups may inform future studies of housing
      related prevention strategies among SIY. Multi-modal interventions beyond housing
      alone may also be required to prevent sexual morbidity among these vulnerable
      youth. 

PMID- 26208713
TI  - Relevance, valence, and the self-attention network.
AB  - Consistent with the authors' suggestions for research on extensions beyond the
      self (e.g., to joint attention and group-related processes), we offer the
      hypothesis that the Self-Attention Network may facilitate attention to any person
      who is construed as similar to the self along key dimensions. On the basis of
      existing literature and our recent findings, we focus on the dimensions of
      personal relevance and valence. Further research on how these dimensions mediate
      attention to self and others has the potential to unify separate lines of
      research on the neural representation of self and others (i.e., social
      cognition). 

PMID- 26208712
TI  - L- and D-lactate enhance DNA repair and modulate the resistance of cervical
      carcinoma cells to anticancer drugs via histone deacetylase inhibition and
      hydroxycarboxylic acid receptor 1 activation.
AB  - BACKGROUND: The consideration of lactate as an active metabolite is a newly
      emerging and attractive concept. Recently, lactate has been reported to regulate
      gene transcription via the inhibition of histone deacetylases (HDACs) and
      survival of cancer cells via hydroxycarboxylic acid receptor 1 (HCAR1). This
      study examined the role of L- and D-lactate in the DNA damage response in
      cervical cancer cells. METHODS: Three cervical cancer cell lines were examined:
      HeLa, Ca Ski and C33A. The inhibitory activity of lactate on HDACs was analysed
      using Western blot and biochemical methods. The lactate-mediated stimulation of
      DNA repair and cellular resistance to neocarzinostatin, doxorubicin and cisplatin
      were studied using gamma-H2AX, comet and clonogenic assays. HCAR1 and DNA repair
      gene expression was quantified by real-time PCR. DNA-PKcs activity and HCAR1
      protein expression were evaluated via immunocytochemistry and Western blot,
      respectively. HCAR1 activation was investigated by measuring intracellular cAMP
      accumulation and Erk phosphorylation. HCAR1 expression was silenced using shRNA.
      RESULTS: L- and D-lactate inhibited HDACs, induced histone H3 and H4
      hyperacetylation, and decreased chromatin compactness in HeLa cells. Treating
      cells with lactate increased LIG4, NBS1, and APTX expression by nearly 2-fold and
      enhanced DNA-PKcs activity. Based on gamma-H2AX and comet assays, incubation of
      cells in lactate-containing medium increased the DNA repair rate. Furthermore,
      clonogenic assays demonstrated that lactate mediates cellular resistance to
      clinically used chemotherapeutics. Western blot and immunocytochemistry showed
      that all studied cell lines express HCAR1 on the cellular surface. Inhibiting
      HCAR1 function via pertussis toxin pretreatment partially abolished the effects
      of lactate on DNA repair. Down-regulating HCAR1 decreased the efficiency of DNA
      repair, abolished the cellular response to L-lactate and decreased the effect of
      D-lactate. Moreover, HCAR1 shRNA-expressing cells produced significantly lower
      mRNA levels of monocarboxylate transporter 4. Finally, the enhancement of DNA
      repair and cell survival by lactate was suppressed by pharmacologically
      inhibiting monocarboxylate transporters using the inhibitor alpha-cyano-4
      hydroxycinnamic acid (alpha-CHCA). CONCLUSIONS: Our data indicate that L- and D
      lactate present in the uterine cervix may participate in the modulation of
      cellular DNA damage repair processes and in the resistance of cervical carcinoma
      cells to anticancer therapy.

PMID- 26208714
TI  - Erosive esophageal reflux vs. non erosive esophageal reflux: oral findings in 71
      patients.
AB  - BACKGROUND: The purpose of this clinical study was to assess the prevalence of
      acidic oral mucosal lesions and periodontal conditions in patients suffering from
      erosive esophageal reflux disease (ERD) compared with non erosive esophageal
      reflux disease (NERD) patients, both treated with long term proton pump
      inhibitors (PPI). METHODS: Seventy-one patients with diagnosed GERD were studied:
      i.e. 29 ERD and 42 NERD patients. Thorough visual examination of the oral mucosa
      and a periodontal evaluation was performed. The primary outcome was defined as a
      statistically significant difference, between the two groups, in the presence of
      acidic lesions of the oral mucosa and specific periodontal parameters. RESULTS:
      This study failed to demonstrate statistically significant differences between
      ERD and NERD patients with respect to the prevalence of oral mucosal lesions.
      However, significantly more ERD patients suffered from severe periodontitis (CAL
      >= 5 mm) as compared to NERD patients. Accordingly, it may be assumed that PPI
      use had no adverse effects on the prevalence of acidic oral mucosal lesions and
      on periodontal destruction. CONCLUSIONS: Within the limitations of this study it
      may be concluded that ERD and NERD patients need separate evaluation with respect
      to periodontal destruction. Moreover, long term PPI medication had no adverse
      clinical impact on acidic oral mucosal lesions and periodontal destruction.
      Further studies are necessary to elucidate the role of reflux in the periodontal
      destruction of ERD individuals.

PMID- 26208715
TI  - Favorable outcome of haploidentical hematopoietic stem cell transplantation in
      Philadelphia chromosome-positive acute lymphoblastic leukemia: a multicenter
      study in Southwest China.
AB  - BACKGROUND: Since the introduction of tyrosine kinase inhibitors (TKIs) into
      combination chemotherapy regimens, the majority of newly diagnosed Philadelphia
      chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients have achieved
      complete remission (CR). However, without allogeneic hematopoietic stem cell
      transplantation (HSCT), long-term outcomes in adults remain unsatisfactory.
      Indeed, haploidentical HSCT has become a common treatment for adult patients who
      lack an HLA-matched donor, though limited data are available on the efficacy of
      haploidentical HSCT in Ph+ ALL patients. METHODS: We analyzed the clinical
      outcomes of 82 Ph+ ALL patients who underwent haploidentical HSCT (n = 47) or HLA
      matched HSCT (n = 35). Real-time quantitative reverse transcription polymerase
      chain reaction (qRT-PCR) was performed to assess BCR-ABL expression. All of the
      patients were treated with an imatinib-based regimen before undergoing HSCT.
      Imatinib treatment was resumed in the patients' posttransplantation following
      detection of BCR-ABL transcripts. RESULTS: All of the patients achieved
      neutrophil and platelet engraftment, with the exception of five patients who died
      prior to engraftment. Haploidentical HSCT was associated with higher incidences
      of acute graft-versus-host disease (GVHD) (51.1 vs. 25.7%, p < 0.05) and chronic
      GVHD (48.9 vs. 25.7%, p < 0.05) compared with HLA-matched HSCT, but there was no
      difference in the incidence of either grades III-IV acute GVHD or extensive
      chronic GVHD. The incidence of cytomegalovirus (CMV) infection was significantly
      higher in the patients treated with haploidentical HSCT than in those treated
      with HLA-matched HSCT (38.3 vs. 14.3%, p < 0.05). Haploidentical HSCT was
      associated with a significantly lower relapse rate compared with HLA-matched HSCT
      (44.8 vs. 19.1%, p < 0.05). There were no differences in non-relapse mortality
      (NRM), leukemia-free survival (LFS), or overall survival (OS) between the
      patients who received HLA-matched HSCT and those who underwent haploidentical
      HSCT. CONCLUSIONS: Our data indicate that the incidence of NRM after HSCT is
      similar between the patients who receive HLA-matched donor cells and those who
      receive haploidentical donor cells and that haploidentical HSCT reduces the
      relapse rate. Haploidentical HSCT represents an encouraging treatment option for
      Ph+ ALL patients who lack a suitable HLA-matched donor.

PMID- 26208716
TI  - A novel epidemiological model to better understand and predict the observed
      seasonal spread of Pestivirus in Pyrenean chamois populations.
AB  - Seasonal variations in individual contacts give rise to a complex interplay
      between host demography and pathogen transmission. This is particularly true for
      wild populations, which highly depend on their natural habitat. These seasonal
      cycles induce variations in pathogen transmission. The seasonality of these
      biological processes should therefore be considered to better represent and
      predict pathogen spread. In this study, we sought to better understand how the
      seasonality of both the demography and social contacts of a mountain ungulate
      population impacts the spread of a pestivirus within, and the dynamics of, this
      population. We propose a mathematical model to represent this complex biological
      system. The pestivirus can be transmitted both horizontally through direct
      contact and vertically in utero. Vertical transmission leads to abortion or to
      the birth of persistently infected animals with a short life expectancy.
      Horizontal transmission involves a complex dynamics because of seasonal
      variations in contact among sexes and age classes. We performed a sensitivity
      analysis that identified transmission rates and disease-related mortality as key
      parameters. We then used data from a long-term demographic and epidemiological
      survey of the studied population to estimate these mostly unknown epidemiological
      parameters. Our model adequately represents the system dynamics, observations and
      model predictions showing similar seasonal patterns. We show that the virus has a
      significant impact on population dynamics, and that persistently infected animals
      play a major role in the epidemic dynamics. Modeling the seasonal dynamics
      allowed us to obtain realistic prediction and to identify key parameters of
      transmission.

PMID- 26208717
TI  - Non-contrast coronary artery wall and plaque imaging using inversion-recovery
      prepared steady-state free precession.
AB  - BACKGROUND: The objective of this study was to investigate whether three
      dimensional (3D) single inversion-recovery prepared steady-state free precession
      (IR-SSFP) could characterize the coronary artery wall. METHODS: IR-SSFP was
      scanned on a 1.5-T MR scanner with a five element cardiac coil. One hundred and
      twenty-one subjects with known or suspected coronary artery disease who had
      undergone X-ray coronary angiography (XCA) underwent coronary artery wall imaging
      using IR-SSFP sequences. In each coronary segment, the detection of the coronary
      wall was categorized, and contrast (signal of plaque minus signal of blood in the
      aorta divided by the signal of plaque plus signal of blood in the aorta) was
      calculated. RESULTS: 422 of 517 segments (82%) were successfully visualized, and
      the detection scores tended to be higher at the proximal coronary artery when
      compared with other segments of the coronary artery. High contrast
      (contrast>=0.75) areas were observed in 62 of 218 segments with >=50% coronary
      artery stenosis by XCA but also in 25 of 299 segments without >=50% coronary
      stenosis. CONCLUSIONS: IR-SSFP provided good visualization of the coronary wall.
      This approach represents a promising noninvasive strategy for the assessment of
      the coronary artery wall.

PMID- 26208719
TI  - Case report: successful closure of a large macular hole secondary to uveitis
      using the inverted internal limiting membrane flap technique.
AB  - BACKGROUND: Macular holes (MHs) are one of the complications of posterior uveitis
      that can significantly disturb vision. Conventional MH surgery (vitrectomy,
      internal limiting membrane (ILM) peeling, and gas tamponade) has been reported to
      show lower closure rates in patients with MHs secondary to uveitis than in
      patients with idiopathic MHs. Recently, the inverted ILM flap technique has been
      reported to be effective for treating refractory MHs. Here, we describe the
      application of this technique in a patient with a large MH secondary to uveitis,
      and its successful closure. CASE PRESENTATION: An 80-year-old woman presented
      with a chronic, large MH secondary to uveitis. The minimum aperture diameter of
      the MH was 569 MUm and extensive post-inflammatory chorioretinal atrophy was
      present, which included the juxtafoveal region. Vitrectomy with the inverted ILM
      flap technique assisted by low molecular weight hyaluronic acid was performed.
      Three days after surgery, the MH was closed successfully, without excessive
      gliosis. CONCLUSION: The inverted ILM flap technique may be the preferred
      surgical procedure for the treatment of large MHs secondary to uveitis.

PMID- 26208718
TI  - The pattern of congenital heart defects arising from reduced Tbx5 expression is
      altered in a Down syndrome mouse model.
AB  - BACKGROUND: Nearly half of all individuals with Down Syndrome (DS) have some type
      of congenital heart defect (CHD), suggesting that DS sensitizes to CHD but does
      not cause it. We used a common mouse model of DS, the Ts65Dn mouse, to study the
      contribution of Tbx5, a known modifier of CHD, to heart defects on a trisomic
      backgroun. Mice that were heterozygous for a Tbx5 null allele were crossed with
      Ts65Dn mice. Thoraxes of progeny were fixed in 10% formalin, embedded in
      paraffin, and sectioned for analysis of CHD. Gene expression in embryonic hearts
      was examined by quantitative PCR and in situ hybridization. A TBX5 DNA binding
      site was verified by luciferase assays. METHODS: Mice that were heterozygous for
      a Tbx5 null allele were crossed with Ts65Dn mice. Thoraxes of progeny were fixed
      in 10% formalin, embedded in paraffin, and sectioned for analysis of CHD. Gene
      expression in embryonic hearts was examined by quantitative PCR and in situ
      hybridization. A TBX5 DNA binding site was verified by luciferase assays.
      RESULTS: We crossed mice that were heterozygous for a Tbx5 null allele with
      Ts65Dn mice. Mice that were trisomic and carried the Tbx5 mutation (Ts65Dn;Tbx5
      (+/-) ) had a significantly increased incidence of overriding aorta compared to
      their euploid littermates. Ts65Dn;Tbx5 (+/-) mice also showed reduced expression
      of Pitx2, a molecular marker for the left atrium. Transcript levels of the
      trisomic Adamts1 gene were decreased in Tbx5 (+/-) mice compared to their euploid
      littermates. Evidence of a valid binding site for TBX5 upstream of the trisomic
      Adamts1 locus was also shown. CONCLUSION: Haploinsufficiency of Tbx5 and trisomy
      affects alignment of the aorta and this effect may stem from deviations from
      normal left-right patterning in the heart. We have unveiled a previously unknown
      interaction between the Tbx5 gene and trisomy, suggesting a connection between
      Tbx5 and trisomic genes important during heart development.

PMID- 26208720
TI  - Moral distress in Turkish intensive care nurses.
AB  - BACKGROUND: Moral distress is a common problem among professionals working in the
      field of healthcare. Moral distress is the distress experienced by a professional
      when he or she cannot fulfill the correct action due to several obstacles,
      although he or she is aware of what it is. The level of moral distress
      experienced by nurses working in intensive care units varies from one
      country/culture/institution to another. However, in Turkey, there is neither a
      measurement tool used to assess moral distress suffered by nurses nor a study
      conducted on the issue. AIM/OBJECTIVE: The study aims to (a) validate the Turkish
      version of the Moral Distress Scale-Revised to be used in intensive care units
      and to examine the validity and reliability of the Turkish version of the scale,
      and (b) explore Turkish intensive care nurses' moral distress level. METHOD: The
      sample of this methodological, descriptive, and cross-sectional design study
      comprises 200 nurses working in the intensive care units of internal medicine and
      surgical departments of four hospitals in three cities in Turkey. The data were
      collected with the Socio-Demographic Characteristics Form and The Turkish Version
      of Moral Distress Scale-Revised. Ethical considerations: The study proposal was
      approved by the ethics committee of the Faculty of Medicine, Cumhuriyet
      University. All participating nurses provided informed consent and were assured
      of data confidentiality. RESULTS: In parallel with the original scale, Turkish
      version of Moral Distress Scale-Revised consists of 21 items, and shows a one
      factor structure. It was determined that the moral distress total and item mean
      scores of the nurses participating in the study were 70.81 +/- 48.23 and 3.36 +/-
      4.50, respectively. CONCLUSION: Turkish version of Moral Distress Scale-Revised
      can be used as a reliable and valid measurement tool for the evaluation of moral
      distress experienced by nurses working in intensive care units in Turkey. In line
      with our findings, it can be said that nurses suffered low level of moral
      distress. However, factors which caused the nurses in our study to experience
      higher levels of moral distress are inadequate communication within the team,
      working with professionals they considered as incompetent, and futile care.

PMID- 26208721
TI  - Using video in childbirth research.
AB  - BACKGROUND: Conducting video-research in birth settings raises challenges for
      ethics review boards to view birthing women and research-midwives as capable,
      autonomous decision-makers. AIM: This study aimed to gain an understanding of how
      the ethical approval process was experienced and to chronicle the perceived risks
      and benefits. RESEARCH DESIGN: The Birth Unit Design project was a 2012
      Australian ethnographic study that used video recording to investigate the
      physical design features in the hospital birthing space that might influence both
      verbal and non-verbal communication and the experiences of childbearing women,
      midwives and supporters. Participants and research context: Six women, 11
      midwives and 11 childbirth supporters were filmed during the women's labours in
      hospital birth units and interviewed 6 weeks later. Ethical considerations: The
      study was approved by an Australian Health Research Ethics Committee after a
      protracted process of negotiation. FINDINGS: The ethics committee was influenced
      by a traditional view of research as based on scientific experiments resulting in
      a poor understanding of video-ethnographic research, a paradigmatic view of the
      politics and practicalities of modern childbirth processes, a desire to protect
      institutions from litigation, and what we perceived as a paternalistic approach
      towards protecting participants, one that was at odds with our aim to facilitate
      situations in which women could make flexible, autonomous decisions about how
      they might engage with the research process. DISCUSSION: The perceived need for
      protection was overly burdensome and against the wishes of the participants
      themselves; ultimately, this limited the capacity of the study to improve care
      for women and babies. CONCLUSION: Recommendations are offered for those involved
      in ethical approval processes for qualitative research in childbirth settings.
      The complexity of issues within childbirth settings, as in most modern healthcare
      settings, should be analysed using a variety of research approaches, beyond
      efficacy-style randomised controlled trials, to expand and improve practice-based
      results.

PMID- 26208722
TI  - Technologies in older people's care.
AB  - BACKGROUND: The tension between care-based and technology-based rationalities
      motivates studies concerning how technology can be used in the care sector to
      support the relational foundation of care. OBJECTIVES: This study interprets
      values related to care and technologies connected to the practice of good care.
      RESEARCH DESIGN: This research study was part of a development project aimed at
      developing innovative work practices through information and communication
      technology. Participants and research context: All staff (n = 18) working at two
      wards in a care facility for older people were asked to participate in
      interviews, and 12 accepted. We analysed the data using latent content analysis
      in combination with normative analysis. Ethical considerations: The caregivers
      were informed that participation was voluntary and that they could drop out at
      any time without providing any explanation. FINDINGS: Four values were
      identified: 'presence', 'appreciation', 'competence' and 'trust'. Caregivers
      wanted to focus on care receivers as unique persons, a view that they thought was
      compromised by time-consuming and beeping electronic devices. Appraising from
      next-of-kin and been seen as someone who can contribute together with knowledge
      to handle different situations were other desires. The caregivers also desired
      positive feedback from next-of-kin, as they wanted to be seen as professionals
      who have the knowledge and skills to handle difficult situations. In addition,
      the caregivers wanted their employer to trust them, and they wanted to work in a
      calm environment. DISCUSSION: Caregivers' desire for disturbance-free
      interactions, being valued for their skills and working in a trustful working
      environment were interpreted as their base for providing good care. The
      caregivers' arguments are based on caring rationality, and sometimes they felt
      the technological rationality interfered with their main mission, providing
      quality care. CONCLUSION: Introducing new technology in caring should support the
      caring relationship. Although society's overall technology-based approach may
      have gained popularity as a problem solver, technology-based rationality may
      compromise a care-based rationality. A shift in attitudes towards care as a
      concept on all societal levels is needed.

PMID- 26208724
TI  - Epithelioid Rhabdomyosarcoma; a case report with immunohistochemical and
      molecular study.
AB  - Recently, we encountered a biopsy of epithelioid rabdomyosarcoma with lymph node
      metastasis. A computed tomography (CT) scan showed number of swollen lymph nodes
      in the left neck and a huge abdominal mass occupying the right kidney. In the
      lymph node biopsy, tumor cells showed diffuse sheet-like growth reminiscent of
      carcinoma and melanoma cells with extensive distribution of coagulation necrosis.
      Tumor cells had abundant amphophilic cytoplasm and clear large nuclei. Most tumor
      cells showed severe cytologic atypia manifested in prominent nucleoli and
      pleomorphic nuclei. Tumor cells were focally positive for desmin. Most tumor
      cells showed expressons for vimentin, BAF47 (INI-1), and myogenin. On reverse
      transcriptase polymerase chain reaction (RT-PCR) analysis, tumor cells lacked Myo
      D1 and PAX3/7-FKHR transcripts and showed myogenin transcripts. On cytogenetic
      (karyotypic) analysis, tumor cells showed highly complex karyotypes. The patient
      received various regimens of chemotherapy, but 6 months after the biopsy she died
      with progression of the tumor. Since consent was not obtained, an autopsy was not
      performed. 

PMID- 26208725
TI  - Detection of defect parameters using nonlinear air-coupled emission by ultrasonic
      guided waves at contact acoustic nonlinearities.
AB  - Interaction of ultrasonic guided waves with kissing bonds (closed delaminations
      and incipient surface breaking cracks) gives rise to nonlinear features at the
      defect location. This causes higher harmonic frequency ultrasonic radiation into
      the ambient air, often referred to as Nonlinear Air-Coupled Emission (NACE),
      which may serve as a nonlinear tag to detect the defects. This paper summarizes
      the results of a numerical implementation and simulation study of NACE. The
      developed model combines a 3D time domain model for the nonlinear Lamb wave
      propagation in delaminated samples with a spectral solution for the nonlinear air
      coupled emission. A parametric study is conducted to illustrate the potential of
      detecting defect location, size and shape by studying the NACE acoustic radiation
      patterns in different orientation planes. The simulation results prove that there
      is a good determination potential for the defect parameters, especially when the
      radiated frequency matches one of the resonance frequencies of the delaminated
      layer, leading to a Local Defect Resonance (LDR). 

PMID- 26208726
TI  - Acetate: friend or foe? Efficient production of a sweet protein in Escherichia
      coli BL21 using acetate as a carbon source.
AB  - BACKGROUND: Escherichia coli is, to date, the most used microorganism for the
      production of recombinant proteins and biotechnologically relevant metabolites.
      High density cell cultures allow efficient biomass and protein yields. However,
      their main limitation is the accumulation of acetate as a by-product of
      unbalanced carbon metabolism. Increased concentrations of acetate can inhibit
      cellular growth and recombinant protein production, and many efforts have been
      made to overcome this problem. On the other hand, it is known that E. coli is
      able to grow on acetate as the sole carbon source, although this mechanism has
      never been employed for the production of recombinant proteins. RESULTS: By
      optimization of the fermentation parameters, we have been able to develop a new
      acetate containing medium for the production of a recombinant protein in E. coli
      BL21(DE3). The medium is based on a buffering phosphate system supplemented with
      0.5% yeast extract for essential nutrients and sodium acetate as additional
      carbon source, and it is compatible with lactose induction. We tested these
      culture conditions for the production of MNEI, a single chain derivative of the
      sweet plant protein monellin, with potential for food and beverage industries. We
      noticed that careful oxygenation and pH control were needed for efficient protein
      production. The expression method was also coupled to a faster and more efficient
      purification technique, which allowed us to obtain MNEI with a purity higher than
      99%. CONCLUSIONS: The method introduced represents a new strategy for the
      production of MNEI in E. coli BL21(DE3) with a simple and convenient process, and
      offers a new perspective on the capabilities of this microorganism as a
      biotechnological tool. The conditions employed are potentially scalable to
      industrial processes and require only low-priced reagents, thus dramatically
      lowering production costs on both laboratory and industrial scale. The yield of
      recombinant MNEI in these conditions was the highest to date from E. coli
      cultures, reaching on average ~180 mg/L of culture, versus typical LB/IPTG yields
      of about 30 mg/L.

PMID- 26208727
TI  - Images in emergency medicine. Female with leg lesion. Pyoderma gangrenosum.

PMID- 26208728
TI  - Pyoderma Gangrenosum: An Inside Job.

PMID- 26208723
TI  - LncRNA HOTAIR: A master regulator of chromatin dynamics and cancer.
AB  - Non-coding RNAs (ncRNAs) are emerging classes of regulatory RNA that play key
      roles in various cellular and physiological processes such as in gene regulation,
      chromatin dynamics, cell differentiation, and development. NcRNAs are
      dysregulated in a variety of human disorders including cancers, neurological
      disorders, and immunological disorders. The mechanisms through which ncRNAs
      regulate various biological processes and human diseases still remain elusive.
      HOX antisense intergenic RNA (HOTAIR) is a recently discovered long non-coding
      RNA (lncRNA) that plays critical role in gene regulation and chromatin dynamics,
      appears to be misregulated in a variety of cancers. HOTAIR interacts with key
      epigenetic regulators such as histone methyltransferase PRC2 and histone
      demethylase LSD1 and regulates gene silencing. Here, we have reviewed recent
      advancements in understanding the functions and regulation of HOTAIR and its
      association with cancer and other diseases. 

PMID- 26208729
TI  - The Tipping Point.

PMID- 26208730
TI  - Commentary: Road Traffic Injury: We've Come a Long Way, But Not Far Enough.

PMID- 26208731
TI  - Change of shift. A Note to Self: From an Emergency Department Boarder to a Future
      Emergency Physician.

PMID- 26208732
TI  - Annals Of Emergency Medicine Journal Club. Taking the "Goal-Directed" Out of
      Early Goal-Directed Therapy for Sepsis?: Answers to the March 2015 Journal Club
      Questions.

PMID- 26208733
TI  - Images in emergency medicine. Abdominal pain in an adolescent female. Bilateral
      parovarian cysts with left ovarian torsion and right cyst hemorrhage.

PMID- 26208734
TI  - Interoperable Application Programming Interfaces Can Enable Health Information
      Technology Innovation.

PMID- 26208735
TI  - In reply.

PMID- 26208736
TI  - Prolonged QT Risk Assessment in Antipsychotic Overdose Using the QT Nomogram.

PMID- 26208737
TI  - Time to Abandon the Term "3 in 1" Block.

PMID- 26208738
TI  - In reply.

PMID- 26208739
TI  - Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of
      thymidylate synthase in human colon carcinoma cells.
AB  - PURPOSE: 5-Fluorouracil (5-FU) is the basic chemotherapeutic agent used to treat
      colon cancer. However, the sensitivity of colon cancer cells to 5-FU is limited.
      Gossypol is a polyphenolic extract of cottonseeds. The purpose of this study was
      to investigate the activities and related mechanism of gossypol alone or in
      combination with 5-FU against human colon carcinoma cells. METHODS: The IC50 of
      gossypol or/and 5-FU in vitro was tested by 3-(4,5-dimethyl thiazol-2-yl)-2,5
      diphenyl tetrazolium bromide (MTT) assay, and the drug interaction was analyzed
      using the CalcuSyn method. Cell apoptosis was determined using presidium iodide
      staining and flow cytometric analysis. Western blotting was used to determine the
      expression of proteins. Transient transfection method was used to silence
      protein. RESULTS: The IC50 at 48 h of gossypol in colon cancer cells was 26.11 +/
      1.04 MUmol/L in HT-29 cells, 14.11 +/- 1.08 MUmol/L in HCT116 cells, and 21.83
      +/- 1.05 MUmol/L in RKO cells. When gossypol was combined with 5-FU, a
      synergistic cytotoxic effect was observed in HT-29 cells, HCT116 cells, and RKO
      cells compared with treatment with gossypol or 5-FU alone. The Western blotting
      results indicated that gossypol down-regulated thymidylate synthase (TS) rather
      than thymidine phosphorylase protein expression. Furthermore, the mTOR/p70S6K1
      signaling pathway was inhibited in gossypol-treated colon cancer cells, and
      consequently, cyclin D1 expression was decreased, suggesting an additional
      mechanism of the observed antiproliferative synergistic interactions. All the
      observation was confirmed by silencing TS and inactivating the mTOR/p70S6K1
      signaling pathway by rapamycin, both of which increased the chemo-sensitizing
      efficacy of 5-FU. CONCLUSIONS: These findings suggest that gossypol-mediated down
      regulation of TS, cyclin D1, and the mTOR/p70S6K1 signaling pathways enhances the
      anti-tumor effect of 5-FU. Ultimately, our data exposed a new action for gossypol
      as an enhancer of 5-FU-induced cell growth suppression.

PMID- 26208741
TI  - Fairy Chemicals, 2-Azahypoxanthine and 2-Aza-8-oxohypoxanthine, Regulate
      Carotenoid Accumulation in Citrus Juice Sacs in Vitro.
AB  - "Fairy chemicals", 2-azahypoxanthine (AHX) and 2-aza-8-oxohypoxanthine (AOH), are
      two novel plant-growth regulating compounds isolated from a fairy ring forming
      fungus, Lepista sordida. In the present study, the effects of AHX and AOH on the
      accumulation of carotenoids and expression of genes related to carotenoid
      metabolism were investigated in the juice sacs of Satsuma mandarin (Citrus unshiu
      Marc.) in vitro. The results showed that AHX and AOH regulated carotenoid
      metabolism in the citrus juice sacs. Carotenoid accumulation was induced by AHX
      in the second week and by AOH in the fourth week. In the meanwhile, the
      modification of carotenoid accumulation by the AHX and AOH treatments was highly
      regulated at the transcriptional level. The results presented herein provide new
      information on the functions of AHX and AOH in plants and contribute to
      elucidating the mechanisms by which AHX and AOH stimulate plant growth. 

PMID- 26208740
TI  - Malaria eradication and elimination: views on how to translate a vision into
      reality.
AB  - Although global efforts in the past decade have halved the number of deaths due
      to malaria, there are still an estimated 219 million cases of malaria a year,
      causing more than half a million deaths. In this forum article, we asked experts
      working in malaria research and control to discuss the ways in which malaria
      might eventually be eradicated. Their collective views highlight the challenges
      and opportunities, and explain how multi-factorial and integrated processes could
      eventually make malaria eradication a reality. 

PMID- 26208742
TI  - Percutaneous Cecostomy in Adult Patients: Safety and Quality-of-Life Results.
AB  - PURPOSE: To assess the safety and quality of life in adult patients undergoing
      cecostomy tube placement. MATERIALS AND METHODS: Percutaneous cecostomy was
      performed in 23 adults (10 men and 13 women) with neurogenic bowel for whom
      noninvasive therapeutic approaches for chronic refractory constipation or fecal
      incontinence had failed. Mean patient age was 41 years (range, 19-74 y). A
      retrospective, standardized questionnaire evaluated satisfaction and quality of
      life before and after cecostomy. RESULTS: All 23 cecostomy procedures were
      technically successful with no intraprocedural complications. At a mean follow-up
      of 42 months (range, 1-160 mo), there was one (5%) major complication, a
      pericecal abscess. One or more minor complications in 11 of 23 (48%) patients
      included leaking around the tube (5 of 23; 22%) and partial or complete
      dislodgment of the tube (3 of 23; 13%). In all cases, the cecostomy tube was
      exchanged successfully. Satisfaction scores improved from a mean of 2.2 points
      (range, 0-6 points; median, 1.5) to 7.6 points (range, 4-10 points; median, 8).
      The percentage of patients using laxative softeners decreased from 74% to 40%,
      and patients requiring assistance decreased from 52% to 35% after cecostomy
      placement. CONCLUSIONS: Percutaneous cecostomy is a safe procedure for the
      management of adult patients. Patients are able to achieve greater independence
      in their activities of daily living and are highly satisfied with the outcomes.

PMID- 26208743
TI  - Prehabilitation with Whey Protein Supplementation on Perioperative Functional
      Exercise Capacity in Patients Undergoing Colorectal Resection for Cancer: A Pilot
      Double-Blinded Randomized Placebo-Controlled Trial.
AB  - BACKGROUND: A previous comprehensive prehabilitation program, providing nutrition
      counseling with whey protein supplementation, exercise, and psychological care,
      initiated 4 weeks before colorectal surgery for cancer, improved functional
      capacity before surgery and accelerated functional recovery. Those receiving
      standard of care deteriorated. The specific role of nutritional prehabilitation
      alone on functional recovery is unknown. OBJECTIVE: This study was undertaken to
      estimate the impact of nutrition counseling with whey protein on preoperative
      functional walking capacity and recovery in patients undergoing colorectal
      resection for cancer. DESIGN: We conducted a double-blinded randomized controlled
      trial at a single university-affiliated tertiary center located in Montreal,
      Quebec, Canada. Colon cancer patients (n=48) awaiting elective surgery for
      nonmetastatic disease were randomized to receive either individualized nutrition
      counseling with whey protein supplementation to meet protein needs or
      individualized nutrition counseling with a nonnutritive placebo. Counseling and
      supplementation began 4 weeks before surgery and continued for 4 weeks after
      surgery. MAIN OUTCOME MEASURE: The primary outcome was change in functional
      walking capacity as measured with the 6-minute walk test. The distance was
      recorded at baseline, the day of surgery, and 4 weeks after surgery. A change of
      20 m was considered clinically meaningful. RESULTS: The whey group experienced a
      mean improvement in functional walking capacity before surgery of +20.8 m, with a
      standard deviation of 42.6 m, and the placebo group improved by +1.2 (65.5) m
      (P=0.27). Four weeks after surgery, recovery rates were similar between groups
      (P=0.81). CONCLUSION: Clinically meaningful improvements in functional walking
      capacity were achieved before surgery with whey protein supplementation. These
      pilot results are encouraging and justify larger-scale trials to define the
      specific role of nutrition prehabilitation on functional recovery after surgery.

PMID- 26208744
TI  - Oxytocin in General Anxiety and Social Fear: A Translational Approach.
AB  - The neuropeptide oxytocin (OXT) has been revealed as a profound anxiolytic and
      antistress factor of the brain, besides its many prosocial and reproductive
      effects. Therefore, there is substantial scientific and medical interest in its
      potential therapeutic use for the treatment of psychopathologies associated with
      anxiety, fear, and social dysfunctions, such as generalized anxiety disorder,
      posttraumatic stress disorder, and social anxiety disorder, as well as autism and
      schizophrenia, among others. Focusing on preclinical studies, we review the
      existing evidence for the regulatory capacity of OXT to fine-tune general and
      social anxiety-related behaviors, as well as cued and social fear conditioning
      from a translational perspective. The available evidence from animal and human
      studies substantiates the hypothesis of an imbalance of the endogenous brain OXT
      system in the etiology of anxiety disorders, particularly those with a social
      component such as social anxiety disorder. In addition, such an imbalance of the
      OXT system is also likely to be the consequence of chronic OXT treatment
      resulting in a dose-dependent reduction in OXT receptor availability and
      increased anxiety. 

PMID- 26208745
TI  - Effect of a social defeat experience on prefrontal activity in schizophrenia.
AB  - The social defeat (SD) hypothesis of schizophrenia posits that repeated
      experiences of SD may lead to sensitization of the mesolimbic dopaminergic system
      and to precipitation of psychosis. Based on previous definitions adapted to a
      human experimental paradigm, we prepared a computer simulation of SD to mimic
      this subjective experience. We measured prefrontal cortex (PFC) activity in
      subjects with schizophrenia and healthy controls during exposure to a single SD
      experience with functional near infrared spectroscopy. PFC activity declined in
      both groups. Compared with the control condition, SD exposure was associated with
      a broader decline in left ventromedial, right medial and right lateral PFC
      activity in healthy controls (n=25), and a sharper decline in right ventrolateral
      PFC activity in subjects with schizophrenia (n=25). The activity in the right
      ventrolateral PFC, was significantly lower in patients compared with controls.
      This may be due to a deficiency in emotion regulation or self-control, or it may
      be related to impaired empathy in schizophrenia. Different patterns of brain
      activity during the SD experience in subjects with schizophrenia versus healthy
      controls may provide indirect evidence regarding the SD hypothesis of
      schizophrenia. 

PMID- 26208747
TI  - Female but not male young heavy drinkers display altered performance monitoring.
AB  - Difficulties in monitoring ongoing behaviour may be linked to real-life
      problematic drinking behaviours. Prior research suggests female heavy drinkers in
      particular display greater cognitive control deficits. Here, we examine trial-to
      trial behavioural adaptations in a conflict monitoring task, relative to drinking
      behaviour and sex. Heavy drinkers (n=31, 16 male) and controls (n=35, 18 male)
      completed an Eriksen flanker task while brain electrical activity was recorded.
      For reaction time, error rates, and N2 and P3 amplitude of the event-related
      potential, trial-to-trial conflict adaptation was evidenced by a differential
      response to the current (congruent vs. incongruent) trials dependent on the
      identity of the previous trial. For the proportion of errors, heavy drinkers
      showed increased conflict adaptation compared to controls. Conflict adaptation
      for N2 (indexing monitoring) was larger for female heavy drinkers than controls,
      and the opposite was observed for males. There were no interactions involving
      group or sex for the P3 (indexing inhibition). The results suggest a compensatory
      response, such that heavy drinkers are required to increase performance
      monitoring in order to achieve the same behavioural outcome as controls. We also
      confirm the importance of sex as a factor in the relationship between behavioural
      control and heavy alcohol use. 

PMID- 26208748
TI  - EEG utilization in the medical/surgical ICU: a single centre prospective
      observational study.

PMID- 26208746
TI  - Altered threat and safety neural processing linked to persecutory delusions in
      schizophrenia: a two-task fMRI study.
AB  - Persecutory delusions are a clinically important symptom in schizophrenia
      associated with social avoidance and increased violence. Few studies have
      investigated the neurobiology of persecutory delusions, which is a prerequisite
      for developing novel treatments. The aim of this two-paradigm functional magnetic
      resonance imaging (fMRI) study is to characterize social "real world" and
      linguistic threat brain activations linked to persecutory delusions in
      schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms.
      Instructed-fear/safety activations correlated to persecutory delusion severity
      demonstrated significant increased lateral orbitofrontal cortex and visual
      association cortex activations for the instructed-fear vs. safety and instructed
      fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral
      occipital-temporal cortex activations were observed for the instructed-safety
      stimuli vs. baseline contrast. The salience network also showed divergent fear
      and safety cued activations correlated to persecutory delusions. Emotional word
      paradigm analyses showed positive correlations between persecutory delusion
      severity and left-lateralized linguistic and hippocampal-parahippocampal
      activations for the threat vs. neutral word contrast. Visual word form area
      activations correlated positively with persecutory delusions for both threat and
      neutral word vs. baseline contrasts. This study links persecutory delusions to
      enhanced neural processing of threatening stimuli and decreased processing of
      safety cues, and helps elucidate systems-level activations associated with
      persecutory delusions in schizophrenia. 

PMID- 26208749
TI  - Incidence and impact outcome of hyperglycaemia in severe scorpion envenomed
      children requiring intensive care admission.

PMID- 26208750
TI  - Length-dependent innate antiviral effects of double-stranded RNA in the rainbow
      trout (Oncorhynchus mykiss) cell line, RTG-2.
AB  - Effectively all viruses produce long dsRNA during their replicative cycle. In
      mammals long dsRNA molecules induce a robust response through the production of
      type 1 interferon, interferon-stimulated genes (ISGs) and an antiviral state.
      This response is less well understood in fish. We investigated the ability of a
      rainbow trout cell line, RTG-2, to respond to two different lengths of in vitro
      transcribed dsRNA (200 bp and 1264 bp) based on the viral hemorrhagic septicemia
      virus genomic sequence, and high and low molecular weight poly I:C (synthetic
      dsRNA). To explore the innate immune response we used qRT-PCR to measure immune
      gene transcript levels, an ISG-promoter reporter assay, and an antiviral
      protection assay. We saw a significantly greater immune response in all assays in
      response to the longer dsRNA molecule compared to their shorter counterpart. We
      saw significantly more interferon and ISG transcripts, stronger induction of a
      protective antiviral state, and more robust activation of the ISG-promoter. This
      response was not found to be due to a better uptake of the longer dsRNA molecules
      as a cellular uptake assay showed no differences between lengths. These data
      suggest that dsRNA-mediated innate immune responses are length-dependent and
      longer molecules induce a more robust response. There were also some differences
      in the cells response to in vitro transcribed dsRNA compared to poly I:C. This
      provides important information for potential dsRNA-based antiviral therapies and
      vaccine adjuvants.

PMID- 26208751
TI  - Cytokine effects and cellular signaling pathways of grass carp HSP70 in head
      kidney leukocytes.
AB  - In mammals, the cytokine effects of heat shock protein 70 (HSP70) have been well
      documented. However, the precise role and molecular mechanism of fish HSP70 in
      cytokine production are poorly understood. In the present study, recombinant
      grass carp HSP70 (rgcHSP70) was prepared by using the E. coli expression system
      and its effect on interleukin (IL)-1beta (gcil1beta) and tumor necrosis factor
      (TNF)-alpha (gctnfalpha) mRNA expression was examined in grass carp head kidney
      leukocytes (HKLs). Compared with its heated-inactivated protein, rgcHSP70
      enhanced the mRNA levels of these two cytokines in a dose- and time-dependent
      manner. More importantly, the results of enzyme-linked immunoabsorbent assay
      (ELISA) showed that rgcHSP70 markedly stimulated gcIL-1beta and gcTNF-alpha
      secretion from the HKLs, for the first time indicating the ability of HSP70 to
      regulate cytokine release in fish. Moreover, rgcHSP70 displayed more potential to
      increase the cytokines' release instead of their transcription in the same cell
      model. Subsequently, the signaling mechanisms governing the cytokine effect of
      rgcHSP70 were investigated, showing that rgcHSP70-induced gcil1beta mRNA
      expression was suppressed by inhibiting p38 MAPK and NF-kappaB pathways, while
      the stimulation of rgcHSP70 on gctnfalpha mRNA expression were blocked by
      inhibiting JNK MAPK and NF-kappaB pathways. In parallel, rgcHSP70 was also shown
      to activate NF-kappaB pathway through regulating grass carp IkappaBalpha protein
      levels in a time-dependent oscillation. These findings provide further
      understanding of cytokine effect and regulatory mechanism of HSP70 in fish and
      new insights into the roles of HSP70 in teleost immunity.

PMID- 26208752
TI  - Sequestration of RNA by grass carp Ctenopharyngodon idella TIA1 is associated
      with its positive role in facilitating grass carp reovirus infection.
AB  - Previous report demonstrated that grass carp reovirus (GCRV) infection resulted
      in unlinking cellular stress granule formation from aggregation of grass carp
      Ctenopharyngodon idella TIA1 (CiTIA1). Here, we provided evidence to show that
      CiTIA1 bound to synthesized ssRNA and dsRNA in vitro. Both GST-pull down assay
      and RNA immunoprecipitation analysis confirmed the association between GCRV
      specific RNA and GST-tagged CiTIA1 in C. idella kidney (CIK) cells. Furthermore,
      CiTIA1 was shown to protect dsRNA of virus-origin from degradation in CIK cells
      through Northern blot analysis. Finally, transient overexpression of CiTIA1
      enhanced the replication efficiency of GCRV in CIK cells. Taken together, our
      results suggested that cellular CiTIA1 might facilitate GCRV replication through
      sequestrating and protecting viral RNA from degradation.

PMID- 26208753
TI  - Characterization and expression analysis of BCA2 gene in large yellow croaker,
      Larimichthys crocea.
AB  - BCA2, as an E3 ubiquitin ligase, is an important anti-virus immune factor in
      mammals. Up to date, there are not any related reports on BCA2 protein in fishes
      yet. In the present investigation, BCA2 in large yellow croaker Larimichthys
      crocea (named as LcBCA2) was identified and characterized. The full-length cDNA
      of LcBCA2 was 1571 bp, including an ORF of 888 bp encoding a polypeptide of 295
      amino acids. The putative LcBCA2 protein contained a RING-H2 motif at C terminal.
      The LcBCA2 transcripts were broadly distributed in all detected tissues, with
      high expression in muscle, moderate in blood, skin, heart, liver and spleen, weak
      in other tissue as indicated by qPCR analysis. Significant increases were
      observed in skin, gill and spleen after infection of Cryptocaryon irritans, and
      in spleen and head-kidney after inactivated Vibrio. parahaemolyticus, LPS and
      Poly I:C stimulations. Tissue localization by in-situ hybridization showed that
      LcBCA2 mainly expressed in the spleen of the fish in the test group. Our findings
      showed that LcBCA2 inclined to sharply increase in immune organs, especially in
      head-kidney after bacterial and viral stimulations, while in locations (skin and
      gill) of parasites infections, suggesting that BCA2 may play an important role in
      fish defense against bacteria, virus and parasites infections, but the immune
      mechanisms is are different.

PMID- 26208754
TI  - IFNa of black carp is an antiviral cytokine modified with N-linked glycosylation.
AB  - Type I interferons (IFNs) play an important role in the antiviral immune response
      in teleost fish. In this study, one type I interferon (bcIFNa) of black carp
      (Mylopharyngodon piceus) has been cloned and characterized. The full-length cDNA
      of bcIFNa gene consists of 783 nucleotides and the predicted bcIFNa protein
      contains 185 amino acids. Semi-quantitative RT-PCR analysis demonstrated that
      bcIFNa mRNA transcription level in all the selected tissues of black carp was
      greatly increased at 33 h post spring viremia of carp virus (SVCV) infection. The
      protein of bcIFNa could be detected in both the whole cell lysate and the
      supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa
      through immunoblot assay. EPC cells showed greatly increased antiviral ability
      when the cells were treated with the bcIFNa-containing conditioned media for 24 h
      before SVCV infection. Mass spectrum assay and glycosidase digestion analysis
      determined that bcIFNa is modified with N-linked glycosylation, which occurs on
      the Asn (N) of 38 site of this cytokine. The un-glycosylated mutant bcIFNa-N38Q
      could be secreted out of the cell and showed the similar antiviral ability
      against SVCV as that of wild type bcIFNa, which suggested that N-linked
      glycosylation does not contribute directly to the antiviral property of this fish
      cytokine.

PMID- 26208755
TI  - Isolation and characterization of two novel C-type lectins from the oriental
      river prawn, Macrobrachium nipponense.
AB  - C-type lectins are a family of calcium-dependent carbohydrate-binding proteins
      which are believed to play important roles in the innate immunity of
      invertebrates. This study identified two novel C-type lectins, designated as
      MnCTLDcp2 and MnCTLDcp3, from the oriental river prawn Macrobrachium nipponense.
      The full-length cDNA of MnCTLDcp2 was of 1582 bp with an open reading frame (ORF)
      of 972 bp encoding a polypeptide of 323 amino acids. The complete nucleotide
      sequence of MnCTLDcp3 cDNA was 583 bp, containing a 555 bp ORF encoding a
      putative protein of 184 deduced amino acids. The deduced MnCTLDcp2 and MnCTLDcp3
      proteins both contained a single C-type lectin-like domain (CTLD). Besides,
      MnCTLDcp2 contains a signal peptide and an low-density lipoprotein receptor class
      A (LDLa) domain. Reverse transcription PCR showed that MnCTLDcp2 was expressed in
      the heart, gill, nerve hepatopancreas and intestine; MnCTLDcp3 was expressed in
      the hepatopancreas, heart, nerve, gill and muscle. Their expression in the heart
      tissue was regulated following challenge with bacteria. The microbial
      agglutination assay showed that both MnCTLDcp2 and MnCTLDcp3 could agglutinated
      bacteria in the presence of calcium. All these results suggested that MnCTLDcp2
      and MnCTLDcp3 functioned as pattern recognition receptors in the immune system of
      M. nipponense.

PMID- 26208756
TI  - Diffusion-driven proton exchange membrane fuel cell for converting fermenting
      biomass to electricity.
AB  - A membrane-integrated proton exchange membrane fuel cell that enables in situ
      fermentation of sugar to ethanol, diffusion-driven separation of ethanol, and its
      catalytic oxidation in a single continuous process is reported. The fuel cell
      consists of a fermentation chamber coupled to a direct ethanol fuel cell. The
      anode and fermentation chambers are separated by a reverse osmosis (RO) membrane.
      Ethanol generated from fermented biomass in the fermentation chamber diffuses
      through the RO membrane into a glucose solution contained in the DEFC anode
      chamber. The glucose solution is osmotically neutral to the biomass solution in
      the fermentation chamber preventing the anode chamber from drying out. The fuel
      cell sustains >1.3 mW cm(-2) at 47 degrees C with high discharge capacity. No
      separate purification or dilution is necessary, resulting in an efficient and
      portable system for direct conversion of fermenting biomass to electricity.

PMID- 26208757
TI  - Asthma-associated comorbidities in children with and without secondhand smoke
      exposure.
AB  - BACKGROUND: Secondhand smoke (SHS) exposure is known to trigger asthma, but
      asthma disease severity and comorbidities in children exposed to SHS are not very
      well quantified. OBJECTIVE: To identify comorbidities and understand health care
      usage in children with asthma exposed to SHS (cases) compared with children with
      asthma but without SHS exposure (controls). METHODS: A retrospective nested
      matched case-and-control study was conducted with children 5 to 18 years old who
      were enrolled in the Pediatric Asthma Management Program. Pulmonary function
      testing (spirometry, methacholine challenges, and exhaled nitric oxide) and body
      mass index were reviewed. Influenza vaccination rates, oral steroid usage,
      emergency department visits, and hospitalizations were assessed. Network analysis
      of the 2 groups also was conducted to evaluate for any associations between the
      variables. RESULTS: Cases had significantly higher body mass index percentiles
      (>75%, odds ratio [OR] 1.64, 95% confidence interval [CI] 1.22-2.2, P = .001).
      Cases were less likely to have had a methacholine challenge (OR 0.49, 95% CI 0.36
      0.68, P < .001) and an exhaled nitric oxide (OR 0.6, 95% CI 0.37-0.97, P = .04)
      performed than controls. The ratio of forced expiration volume in 1 second to
      forced vital capacity and forced expiration volume in 1 second were lower in
      cases than in controls (P < .05). Cases were less likely to have received an
      influenza vaccination (OR 0.61, 95% CI 0.45-0.82, P = .001) than controls.
      Unsupervised multivariable network analysis suggested a lack of discrete and
      unique subgroups between cases and controls. CONCLUSION: Children with asthma
      exposed to SHS are more likely to have comorbid conditions such as obesity, more
      severe asthma, and less health care usage than those not exposed to SHS. Smoking
      cessation interventions and addressing health disparities could be crucial in
      this vulnerable population.

PMID- 26208759
TI  - Association between specific IgE to Staphylococcus aureus enterotoxins A and B
      and asthma control.
AB  - BACKGROUND: Recent studies have found that serum levels of Staphylococcus aureus
      enterotoxin (SE)-IgE are higher in patients with severe asthma compared with
      patients with nonsevere asthma. However, the association between SE-IgE and
      asthma control is not fully understood. Furthermore, SEA and SEB were the first
      reported SEs and subdivided into different groups. The influences of SEA-IgE and
      SEB-IgE on asthma control have not been elucidated. OBJECTIVE: To determine the
      relevance of SEA- and SEB-IgE in patients with adult asthma and to investigate
      the association of SEA-IgE, SEB-IgE, and asthma control, respectively. METHODS:
      The serum concentrations of SEA- and SEB-IgE in 172 adults with asthma were
      measured with a fluorescent enzyme immunoassay. RESULTS: The prevalence of SEA-
      and SEB-IgE was 16.2% and 22.1%, respectively. Total IgE levels and the
      prevalence of atopic dermatitis were higher in SEA-IgE- and SEB-IgE-positive
      patients than in SEA-IgE- and SEB-IgE-negative patients, respectively; more SEA
      IgE- and SEB-IgE-positive patients owned pets. Sensitization to SEA was
      associated with a younger mean age and a younger mean age at asthma onset.
      Multiple regression analysis indicated an association between total IgE levels
      and SEB-IgE. The prevalence of poorly uncontrolled asthma was significantly
      higher in SEA-IgE-positive patients than in SEA-IgE-negative patients. In
      addition, fractional exhaled nitric oxide levels were higher in SEA-IgE-positive
      patients than in SEA-IgE-negative patients. Logistic regression analysis also
      identified an association between SEA-IgE and poor asthma control. CONCLUSION:
      Our findings indicate that sensitization to SE, in particular SEA rather than
      SEB, is associated with poor asthma control in adults with asthma.

PMID- 26208761
TI  - Moving Toward Conscious Pain Processing Detection in Chronic Disorders of
      Consciousness: Anterior Cingulate Cortex Neuromodulation.
AB  - It has been assumed that patients with chronic disorders of consciousness (DOC)
      do not feel pain, but it is possible that some of them just cannot report it.
      Modulation of gamma-band oscillatory activity (gammaBO) in centroparietal areas
      (considered as a marker of either subjective pain perception processes or pain
      related motor behavior preparation) by part of the anterior cingulate cortex
      (ACC) has been proposed to be suggestive of conscious pain perception and could
      therefore be used to assess the maintenance of some level of conscious pain
      perception in patients with DOC. Hence, we used a repetitive transcranial
      magnetic stimulation (rTMS) approach in an attempt to trigger frontoparietal
      output. We enrolled 10 healthy participants (HC), 10 patients in a minimally
      conscious state (MCS), and 10 with unresponsive wakefulness syndrome (UWS), who
      underwent a 1-Hz rTMS protocol over ACC. Before and after the neurostimulation
      paradigm, we measured the pain-rating assessment (pVAS), gammaBO, latency, and
      the amplitude of cortical nociceptive potentials evoked by transcutaneous
      electric sinusoidal stimuli (EEP). In all the HC and MCS and in 2 of the UWS
      subjects, rTMS increased gammaBO and reduced the EEP amplitude, whereas pVAS
      scoring improved in the HC. Our findings provide some evidence about conscious
      pain processing even in patients with severe DOC and show that rTMS over ACC may
      be a useful approach to better investigate the level of conscious impairment.
      PERSPECTIVE: Patients with DOC may not be able to respond to pain stimuli,
      although they may feel it. The possibility of detecting residual pain perceptions
      by means of a noninvasive neuromodulation paradigm, studying the correlation
      between the ACC and centroparietal gammaBO, may help clinicians to better assess
      pain in such individuals.

PMID- 26208758
TI  - Significant predictors of poor quality of life in older asthmatics.
AB  - BACKGROUND: Morbidity and mortality from asthma are high in older adults and
      quality of life (QOL) might be lower, although standardized measurements of QOL
      have not been validated in this population. OBJECTIVE: To determine predictors of
      asthma-related QOL in older adults. METHODS: Allergy and pulmonary outpatients (n
      = 164) at least 65 years old with an objective diagnosis of asthma completed the
      Mini-Asthma Quality of Life Questionnaire (mAQLQ). Demographics, medical history,
      and mean value for daily elemental carbon attributable to traffic, a surrogate
      for diesel exposure, were obtained. Regression analysis was used to determine
      predictors of mAQLQ scores. RESULTS: Total mAQLQ (mean +/- SD 5.4 +/- 1.1) and
      symptom, emotional, and activity domain scores were similar to those of younger
      populations, whereas environmental domain scores (4.4 +/- 1.7) appeared lower.
      Poorer mAQLQ scores were significantly associated with emergency department
      visits (adjusted beta [abeta] = -1.3, where beta values indicate the strength and
      direction of association, P < .0001) and with poorer scores on the Asthma Control
      Questionnaire (abeta = -0.7, P < .0001). Greater ECAT exposure (abeta = -1.6, P <
      .02), female sex (abeta = -0.4, P < .006), body mass index of at least 30 kg/m(2)
      (abeta = -0.4, P < .01), gastroesophageal reflux (abeta = -0.4, P < .01),
      nonatopic status (abeta = -0.5, P < .002), and asthma onset before 40 years of
      age (abeta = -0.5, P < .004) were significantly associated with poorer mAQLQ
      scores. CONCLUSION: The mAQLQ scores in older adults with stable asthma were
      similar to those in younger populations and were predictive of other measurements
      of asthma control, verifying that the mAQLQ is an appropriate tool in older
      adults with asthma. Traffic pollution exposure was the strongest predictor of
      poorer asthma-related QOL in older adults with asthma.

PMID- 26208760
TI  - Probability curves for predicting symptom severity during oral food challenge
      with milk.

PMID- 26208762
TI  - Validation of the Hospital Anxiety and Depression Scale in Patients With Acute
      Low Back Pain.
AB  - The Hospital Anxiety and Depression Scale (HADS) is a self-report instrument used
      to evaluate depression and anxiety in clinical research. The HADS has advantages
      over other assessments of anxiety and depression; it is efficient in assessing
      both anxiety and depression with a total of 14 items, and it was originally
      developed on a general medical rather than psychiatric sample. However, the HADS
      has not been evaluated specifically for use in clinical trials of acute pain.
      Validation analyses were conducted on data from a randomized, double-blind,
      parallel-group study of tapentadol immediate release vs oxycodone immediate
      release for acute low back pain (N = 666). Analyses of psychometric properties,
      internal consistency, convergent validity, assessments of bias, and confirmatory
      factor analysis were conducted on pretreatment data. Additional analyses were
      performed to test the responsiveness and predictive validity of the HADS. Both
      the Anxiety and Depression subscales (1) showed good psychometric properties, (2)
      had high internal consistency, (3) displayed good convergent validity, (4) had no
      unexpected biases, (5) fit the a priori factor structure, and (6) were highly
      sensitive to changes as a result of analgesic treatment. We conclude that the
      HADS is a valid instrument for efficient, low-burden assessment of anxiety and
      depression in clinical trials with an acute low back pain population.
      PERSPECTIVE: Considered together with the results of other recent studies, the
      data suggest that the HADS can provide a valid, responsive, and efficient
      assessment of anxiety and depression in acute low back pain for clinical trials
      and other clinical research examining acute pain populations.

PMID- 26208763
TI  - [Necrotizing pneumonia with a fatal outcome].

PMID- 26208764
TI  - Influence of meteorological conditions on hospital admission in patients with
      acute coronary syndrome with and without ST-segment elevation: Results of the
      AIRACOS study.
AB  - OBJECTIVE: Evaluate whether the meterological parameters affecting revenues in
      patients with ST-segment and non-ST-segment elevation ACS. DESIGN: A prospective
      cohort study was carried out. SETTING: Coronary Care Unit of Hospital
      Universitario de Canarias PATIENTS: We studies a total of 307 consecutive
      patients with a diagnosis of ST-segment and non-ST-segment elevation ACS. We
      analyze the average concentrations of particulate smaller than 10 and 2.5MUm
      diameter, particulate black carbon, the concentrations of gaseous pollutants and
      meteorological parameters (wind speed, temperature, relative humidity and
      atmospheric pressure) that were exposed patients from one day up to 7 days prior
      to admission. INTERVENTIONS: None. VARIABLES OF INTEREST: Demographic, clinical,
      atmospheric particles, concentrations of gaseous pollutants and meterological
      parameters. RESULTS: A total of 138 (45%) patients were classified as ST-segment
      and 169 (55%) as non-ST-segment elevation ACS. No statistically significant
      differences in exposure to atmospheric particles in both groups. Regarding
      meteorological data, we did not find statistically significant differences,
      except for higher atmospheric pressure in ST-segment elevation ACS (999.6+/-2.6
      vs. 998.8+/-2.5 mbar, P=.008). Multivariate analysis showed that atmospheric
      pressure was significant predictor of ST-segment elevation ACS presentation (OR:
      1.14, 95% CI: 1.04-1.24, P=.004). CONCLUSIONS: In the patients who suffer ACS,
      the presence of higher number of atmospheric pressure during the week before the
      event increase the risk that the ST-segment elevation ACS.

PMID- 26208765
TI  - [Ivabradine poisoning with suicide intention].

PMID- 26208766
TI  - Systematic Review and Meta-Analysis in Facial Plastic Surgery.
AB  - Systematic reviews and meta-analyses hold a unique position in the pyramid of
      evidence. They can provide transparent and rigorous summaries to answer many
      clinical questions in facial plastic surgery. They can also identify areas of
      research deficiency, create new knowledge, and support guidelines or policies. A
      well-conducted systematic review follows a structured process to minimize bias
      and ensure reproducibility. When appropriate, a meta-analysis is incorporated to
      provide a statistical synthesis that combines the results of individual studies.
      This powerful quantitative method is becoming more prevalent in facial plastic
      surgery. This article provides a practical framework to understand and conduct
      this valuable type of research. 

PMID- 26208767
TI  - Skin Care.
AB  - Aging skin is among the most common patient concerns in a facial plastic surgery
      practice. Ultraviolet (UV)-induced damage expedites the pace of intrinsic aging,
      resulting in many of the visible signs of aging, such as rough skin texture,
      pigmentation irregularities, fine and deep wrinkling, and inelasticity. Primary
      prevention of UV and environmental damage with proper skin care and the use of
      sunscreen are critical. There is great interest in topically applied products to
      reverse or delay the visible signs of photoaging. We discuss the most common
      topically applied agents for photoaging, reviewing their mechanisms and
      supporting evidence. 

PMID- 26208768
TI  - Evidence-Based Medicine in Laser Medicine for Facial Plastic Surgery.
AB  - In the setting of rapidly changing technology tone must make a decision on
      whether he or she places a premium on being an "early adopter" of technology or
      delay purchasing decisions until there is adequate proof that a particular
      technology is useful. Laser devices are a significant capital expenditure, and
      therefore members of the second group who base their purchasing decisions on
      evidence-based medicine may be able to avoid deploying capitol into a purchase
      that becomes obsolete as quickly as it appeared. 

PMID- 26208769
TI  - Evidence-Based Medicine: Rhinoplasty.
AB  - Evidence-based medicine has become increasingly prominent in the climate of
      modern day healthcare. The practice of evidence-based medicine involves the
      integration of the best available evidence with clinical experience and expertise
      to help guide clinical decision-making. The essential tenets of evidence-based
      medicine can be applied to both functional and aesthetic rhinoplasty. Current
      outcome measures in functional and aesthetic rhinoplasty, including objective,
      subjective, and clinician-reported measures, is summarized and the current data
      is reviewed. 

PMID- 26208770
TI  - An Evidence-Based Approach to Facial Reanimation.
AB  - This article provides an overview of the current state of the art of facial
      reanimation using the best available evidence. Medical, surgical, and physical
      therapy options in acute and long-standing facial palsy are discussed. 

PMID- 26208771
TI  - Evidence-Based Facial Fracture Management.
AB  - With demands for an evidence-based approach to patient care, the management of
      facial fractures will come under increasing scrutiny because there is an overall
      deficiency in higher level clinical evidence. This article reviews the management
      of facial fractures, focusing on an evidence-based approach. It focuses on select
      areas of facial trauma in which there is controversy and presents randomized
      studies and meta-analysis to help define best practice. The article notes the
      many areas where the evidenced-based literature is weak and looks at the future
      of evidence-based facial trauma care. 

PMID- 26208772
TI  - Microvascular Reconstruction: Evidence-Based Procedures.
AB  - Microvascular free tissue transfer is the best modality of replacing composite
      tissue defects with composite vascularized tissue. Wound healing, functional
      reconstruction, rehabilitation, and cosmesis are best accomplished when the
      tissue defect is replaced by free tissue. The reconstructive tissue can be
      tailored to the defect and is harvested from outside the often radiated
      pretreated reconstructive field. Evidence to support the use of free tissue
      transfer in head and neck defects is not of the highest level. This article
      reviews the postoperative monitoring of free tissue transfer, lateral mandibular
      reconstruction (fibula vs radial forearm), and functional outcomes with free
      tissue transfers. 

PMID- 26208773
TI  - Cleft Lip and Palate: An Evidence-Based Review.
AB  - The current article reviews the pertinent literature on the management of cleft
      lip and palate. We review the commonly used surgical techniques for repair,
      adjunctive options for treatment, clinical outcomes, complications, and concerns
      to consider. Throughout the discussion, we state the level of evidence where
      applicable and identify areas for future study. 

PMID- 26208774
TI  - Evidence-Based Medicine in the Treatment of Infantile Hemangiomas.
AB  - Over the past decade, the treatment of infantile hemangiomas has undergone
      dramatic breakthroughs. This review critically evaluates the latest literature
      that supports the myriad treatment options for infantile hemangiomas. It
      chronicles the fading role of steroid therapy and evolution of propranolol use as
      the major treatment modality. Although propranolol is helping this disease become
      more of a medical disease and less of a surgical dilemma, the report also reveals
      a continued search to find nonsystemic treatment options. In summary, this is an
      evidence-based medicine review for the treatment of infantile hemangiomas. 

PMID- 26208775
TI  - Early Practice Focus: Evidence-Based Practice in Facial Plastic Surgery.
AB  - The practice of evidence-based medicine combines physician experience, knowledge
      of current literature, and patient preferences. Different grading systems are
      used to evaluate current levels of evidence and recommendations. A variety of
      common instruments are used to measure outcomes in facial plastic surgery. These
      instruments are used for expert data collection, including assessment of
      pathology and response to treatment, or for patient-reported outcome measures,
      including quality of life, disability, and daily function. Integration of data
      collection requires storage and protection of health information. We provide an
      outline to what is involved in understanding evidence-based medicine and
      incorporating it into daily practice. 

PMID- 26208776
TI  - Evidence-Based Procedures in Facial Plastic and Reconstructive Surgery.

PMID- 26208777
TI  - Statin and the risk of hepatocellular carcinoma and death in a hospital-based
      hepatitis B-infected population: A propensity score landmark analysis.
AB  - BACKGROUND & AIMS: The use of statin in hepatocellular carcinoma (HCC) and death
      prevention is still uncertain among hepatitis B infected (HBV) patients. This
      study aimed to examine the effect of statin on HCC and death in a HBV population.
      METHODS: We conducted a hospital-based population study of HBV patients, using
      the Hospital Authority database in Hong Kong. We defined statin use by landmark
      analysis to abrogate "immortal time bias" and propensity score (PS) weighting to
      minimize baseline confounders and "indication bias". Multiple imputations for
      missing data were performed. The weighted Cox regression analyses was performed
      for the risk of HCC (adjusting for competing mortality) and death. RESULTS: A
      total of 73,499 patients with a crude HCC incidence of 1.75 per 100 patient-years
      were entered into the 2-year landmark analysis. After landmark analysis and PS
      weighting of baseline covariates, statin users had a 32% risk reduction in HCC
      (weighted sub-hazard ratio (SHR) 0.68; 95% CI 0.48-0.97) compared to non-users.
      There was no decreased risk of death in statin users (weighted HR 0.92; 0.76
      1.11, p=0.386). In subgroup analysis, concurrent statin and nucleos(t)ide
      analogue (NA) use was associated with 59% risk reduction in HCC (weighted SHR
      0.41; 0.19-0.89, p=0.023) compared to NA use alone. CONCLUSION: In this HBV
      cohort adjusted for confounders and biases, statin use is associated with reduced
      HCC risk by 32%. Additive HCC chemopreventive effect was seen with the
      concomitant use of NA and statin. Further prospective studies are warranted to
      investigate the potential use of statin in NA users.

PMID- 26208778
TI  - Long-term live imaging reveals cytosolic immune responses of host hepatocytes
      against Plasmodium infection and parasite escape mechanisms.
AB  - Plasmodium parasites are transmitted by Anopheles mosquitoes to the mammalian
      host and actively infect hepatocytes after passive transport in the bloodstream
      to the liver. In their target host hepatocyte, parasites reside within a
      parasitophorous vacuole (PV). In the present study it was shown that the
      parasitophorous vacuole membrane (PVM) can be targeted by autophagy marker
      proteins LC3, ubiquitin, and SQSTM1/p62 as well as by lysosomes in a process
      resembling selective autophagy. The dynamics of autophagy marker proteins in
      individual Plasmodium berghei-infected hepatocytes were followed by live imaging
      throughout the entire development of the parasite in the liver. Although the host
      cell very efficiently recognized the invading parasite in its vacuole, the
      majority of parasites survived this initial attack. Successful parasite
      development correlated with the gradual loss of all analyzed autophagy marker
      proteins and associated lysosomes from the PVM. However, other autophagic events
      like nonselective canonical autophagy in the host cell continued. This was
      indicated as LC3, although not labeling the PVM anymore, still localized to
      autophagosomes in the infected host cell. It appears that growing parasites even
      benefit from this form of nonselective host cell autophagy as an additional
      source of nutrients, as in host cells deficient for autophagy, parasite growth
      was retarded and could partly be rescued by the supply of additional amino acid
      in the medium. Importantly, mouse infections with P. berghei sporozoites
      confirmed LC3 dynamics, the positive effect of autophagy activation on parasite
      growth, and negative effects upon autophagy inhibition. 

PMID- 26208779
TI  - SOD2 targeted gene editing by CRISPR/Cas9 yields Human cells devoid of MnSOD.
AB  - To date no models exist to study MnSOD deficiency in human cells. To address this
      deficiency, we created a SOD2-null human cell line that is completely devoid of
      detectable MnSOD protein expression and enzyme activity. We utilized the
      CRISPR/Cas9 system to generate biallelic SOD2 disruption in HEK293T cells. These
      SOD2-null cells exhibit impaired clonogenic activity, which was rescued by either
      treatment with GC4419, a pharmacological small-molecule mimic of SOD, or growth
      in hypoxia. The phenotype of these cells is primarily characterized by impaired
      mitochondrial bioenergetics. The SOD2-null cells displayed perturbations in their
      mitochondrial ultrastructure and preferred glycolysis as opposed to oxidative
      phosphorylation to generate ATP. The activities of mitochondrial complex I and II
      were both significantly impaired by the absence of MnSOD activity, presumably
      from disruption of the Fe/S centers in NADH dehydrogenase and succinate
      dehydrogenase subunit B by the aberrant redox state in the mitochondrial matrix
      of SOD2-null cells. By creating this model we provide a novel tool with which to
      study the consequences of lack of MnSOD activity in human cells. 

PMID- 26208780
TI  - IFN-gamma-induced macrophage antileishmanial mechanisms in mice: A role for
      immunity-related GTPases, Irgm1 and Irgm3, in Leishmania donovani infection in
      the liver.
AB  - In C57BL/6 mice, Leishmania donovani infection in the liver provoked IFN-gamma
      induced expression of the immunity-related GTPases (IRG), Irgm1 and Irgm3. To
      gauge the antileishmanial effects of these macrophage factors in the liver,
      intracellular infection was analyzed in IRG-deficient mice. In early- (but not
      late-) stage infection, Irgm3(-/-) mice failed to properly control parasite
      replication, generated little tissue inflammation and were hyporesponsive to
      pentavalent antimony (Sb) chemotherapy. Observations limited to early-stage
      infection in Irgm1(-/-) mice demonstrated increased susceptibility and virtually
      no inflammatory cell recruitment to heavily-parasitized parenchymal foci but an
      intact response to chemotherapy. In L. donovani infection in the liver, the
      absence of either Irgm1 or Irgm3 impairs early inflammation and initial
      resistance; the absence of Irgm3, but not Irgm1, also appears to impair the
      intracellular efficacy of Sb chemotherapy. 

PMID- 26208781
TI  - Duddingtonia flagrans in the control of gastrointestinal nematodes of horses.
AB  - Horses can harbor a large amount of parasites that may cause serious clinical
      signs even death. The aim of this study was to evaluate the predatory activity of
      the fungus Duddingtonia flagrans against infective larvae (L3) of
      gastrointestinal nematodes of horses in fecal culture. The experimental design
      was completely randomized with three treated groups (G1, G2 and G3) and one
      control (CG), using eight animals/group. The treated animals received G1: 1.5 *
      10(5); G2: 3 * 10(5) and G3: 6 * 10(5) chlamydospores of D. flagrans/kg body
      weight during 21 days. The fungi preparation was given at every other three-day
      interval. Faecal samples were collected during 30 days, on the same interval, to
      perform the fecal egg counts (EPG) and fecal culture for each horse. All groups
      demonstrated similar results for the EPG (P > 0.05) counts. D. flagrans
      significantly reduced (P < 0.05) the number of infective larvae after 72 h
      interval between treatments. The G2 and G3 promoted higher results (P < 0.05) of
      L3 reduction compared to the CG. The biological control with the predacious fungi
      D. flagrans is still a promising free-living parasite regulator alternative to be
      use in livestock. 

PMID- 26208782
TI  - Idioms of Distress Among Depressed White-Non-Mexican and Mexican-Origin Older
      Men.
AB  - Older men are less likely than older women to receive depression treatment.
      Latino older men in particular have been found to have significantly lower rates
      of depression treatment than their white-non-Mexican (WNM) counterparts. Prior
      research has shown that men are less likely than women to express overt affect
      and/or report depression symptoms that may prompt primary care physicians'
      inquiry about depression. Previous studies have overlooked the idioms of distress
      common among older men. This study investigates: a) the range of idioms of
      distress that emerge in the narratives of depressed older men, and b) the use of
      these idioms among depressed WNM and Mexican-origin older men. The present report
      is based on qualitative data collected through the Men's Health and Aging Study
      (MeHAS), a mixed-method study of clinically depressed WNM and Mexican-origin
      older (65 and above) men recruited in primary care settings. Qualitative analysis
      of 77 interviews led to identification of idioms of distress and informed idiom
      categories. Study findings show that: a) both groups of men utilized a range of
      idioms of distress that met current DSM criteria for depression, b) both groups
      were also likely to utilize idioms that feel outside clinical depression
      criteria, and c) there were similarities as well as differences between WNM and
      Mexican-origin men. This study provides a larger vocabulary that clinicians might
      consider in recognizing depression and initiating depression care for older men
      from diverse ethnic backgrounds. This is important to improve depression care
      among older men in general and those of Mexican-origin in particular. 

PMID- 26208783
TI  - Cholinergic modulation of dopamine pathways through nicotinic acetylcholine
      receptors.
AB  - Nicotine addiction is highly prevalent in current society and is often comorbid
      with other diseases. In the central nervous system, nicotine acts as an agonist
      for nicotinic acetylcholine receptors (nAChRs) and its effects depend on location
      and receptor composition. Although nicotinic receptors are found in most brain
      regions, many studies on addiction have focused on the mesolimbic system and its
      reported behavioral correlates such as reward processing and reinforcement
      learning. Profound modulatory cholinergic input from the pedunculopontine and
      laterodorsal tegmentum to dopaminergic midbrain nuclei as well as local
      cholinergic interneuron projections to dopamine neuron axons in the striatum may
      play a major role in the effects of nicotine. Moreover, an indirect
      mesocorticolimbic feedback loop involving the medial prefrontal cortex may be
      involved in behavioral characteristics of nicotine addiction. Therefore, this
      review will highlight current understanding of the effects of nicotine on the
      function of mesolimbic and mesocortical dopamine projections in the
      mesocorticolimbic circuit. 

PMID- 26208784
TI  - Guidelines for manuscript submission in the peer-reviewed pharmacological
      literature.
AB  - Recent reports have highlighted studies in biomedical research that cannot be
      reproduced, tending to undermine the credibility, relevance and sustainability of
      the research process. To address this issue, a number of factors can be monitored
      to improve the overall probability of reproducibility. These include: (i)
      shortcomings in experimental design and execution that involve hypothesis
      conceptualization, statistical analysis, and data reporting; (ii) investigator
      bias and error; (iii) validation of reagents including cells and antibodies; and
      (iv) fraud. Historically, research data that have undergone peer review and are
      subsequently published are then subject to independent replication via the
      process of self-correction. This often leads to refutation of the original
      findings and retraction of the paper by which time considerable resources have
      been wasted in follow-on studies. New NIH guidelines focused on experimental
      conduct and manuscript submission are being widely adopted in the peer-reviewed
      literature. These, in their various iterations, are intended to improve the
      transparency and accuracy of data reporting via the use of checklists that are
      often accompanied by "best practice" guidelines that aid in validating the
      methodologies and reagents used in data generation. The present Editorial
      provides background and context to a newly developed checklist for submissions to
      Biochemical Pharmacology that is intended to be clear, logical, useful and
      unambiguous in assisting authors in preparing manuscripts and in facilitating the
      peer review process. While currently optional, development of this checklist
      based on user feedback will result in it being mandatory within the next 12
      months. 

PMID- 26208785
TI  - Low-dose copper infusion into the coronary circulation induces acute heart
      failure in diabetic rats: New mechanism of heart disease.
AB  - Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu
      excretion in patients with established cardiovascular disease; it also causes
      cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis
      in rats. However, the mechanisms that link impaired Cu regulation to cardiac
      dysfunction in diabetes are incompletely understood. Chronic treatment with
      triethylenetetramine (TETA), a Cu2+-selective chelator, improves cardiac function
      in diabetic patients, and in rats with heart disease; the latter displayed ~3
      fold elevations in free Cu2+ in the coronary effluent when TETA was infused into
      their coronary arteries. To further study the nature of defective cardiac Cu
      regulation in diabetes, we employed an isolated-perfused, working-heart model in
      which we infused micromolar doses of Cu2+ into the coronary arteries and measured
      acute effects on cardiac function in diabetic and non-diabetic-control rats.
      Infusion of CuCl2 solutions caused acute dose-dependent cardiac dysfunction in
      normal hearts. Several measures of baseline cardiac function were impaired in
      diabetic hearts, and these defects were exacerbated by low-micromolar Cu2+
      infusion. The response to infused Cu2+ was augmented in diabetic hearts, which
      became defective at lower infusion levels and underwent complete pump failure
      (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only
      moderately impaired function of control hearts. To our knowledge, this is the
      first report describing the acute effects on cardiac function of
      pathophysiological elevations in coronary Cu2+. The effects of Cu2+ infusion
      occur within minutes in both control and diabetic hearts, which suggests that
      they are not due to remodelling. Heightened sensitivity to the acute effects of
      small elevations in Cu2+ could contribute substantively to impaired cardiac
      function in patients with diabetes and is thus identified as a new mechanism of
      heart disease.

PMID- 26208786
TI  - Whole blood and apheresis donors in Quebec, Canada: Demographic differences and
      motivations to donate.
AB  - This study sought to compare demographics and donation motivations among
      plasma/platelet donors (PPDs) and whole blood donors (WBDs), in a voluntary and
      non-remunerated context. Motives to donate blood and demographic characteristics
      were collected through questionnaires completed by 795 WBDs and 473 PPDs.
      Comparison of WBDs and PPDs under chi-square tests showed that 17 out of 23
      motivators were statistically different according to various demographic
      variables. These results demonstrate the existence of specific donor profiles
      both for WBDs and PPDs. Agencies should develop new recruitment strategies
      tailored to these donors, especially if they wish to convince WBDs to convert to
      apheresis donation. 

PMID- 26208787
TI  - Leukapheresis for autologous stem cell transplantation: Comparative study of two
      different thawing methods WSCFD((r)) Stem Cell Fast Thawer KW versus 37  degrees
      C thermostatic bath.
AB  - BACKGROUND: Leukapheresis for autologous stem cell transplantation represents an
      efficient technique for the reconstitution of haematopoietic system in patients
      subjected to a high-dose chemotherapy for the treatment of haematological
      malignancies. The current regulations emphasise first steps of leukapheresis
      procedure but do not recommend methods for thawing, only suggesting that it must
      be performed as soon as possible in a 37  degrees C thermostatic bath. AIM OF THE
      STUDY: We compared the classic method of thawing with an innovative and fully
      traceable method that uses WSCFD((r)) Stem Cell Fast Thawer KW. MATERIALS AND
      METHODS: The first part of the study was focused on the thermodynamic process of
      the two methods, thawing 6 "simulated" leukapheresis (buffy coats of healthy
      donors cryopreserved with saline solution, 5% HSA and 5% DMSO) and analysing the
      thawing curve obtained, by using an inside probe. In the second part, we focused
      on the recovery of viable CD34+ cells and leukocytes, thawing 20 real
      leukapheresis from paediatric patients. In this phase we also analyse final core
      bag temperature, time of procedure, cellular recovery with ISHAGE single platform
      flow cytometry assay and clonogenic potential performing a CFU assay. RESULTS: We
      found no significant differences between the two methods, both for thermodynamic
      aspect and cellular recovery. Thawing curves were similar and the paired
      Student's-t test used for statistical analysis showed a CD34+ cells recovery of
      92.2% +/- 11.4 using WSCFD((r)) versus 90% +/- 11.1 of thermostatic bath. Data
      were similar even for leukocytes recovery (80.8% +/- 9.5 with WSCFD((r)) and
      79.2% +/- 14.4 with thermostatic bath). All thawed products never exceeded the
      core temperature of 30  degrees C and no differences were found about the post
      thaw clonogenic potential (614 * 10(4) +/- 98.3 total CFU using WSCFD((r)) versus
      592 * 10(4) +/- 78.5 using thermostatic bath). The only difference observed was
      about the thawing time: WSCFD method requires a slightly longer time but, on the
      other hand, it correlates with reduced mean increase in temperature per minute,
      as a result of a more linear thawing curve. CONCLUSIONS: WSCFD((r)) can replace
      the 37  degrees C thermostatic bath thawing procedure for leukapheresis,
      providing more security and fully traceable process data.

PMID- 26208789
TI  - Depression among unaccompanied minor refugees: the relative contribution of
      general and acculturation-specific daily hassles.
AB  - OBJECTIVES: This study is designed to provide an empirical conceptualization of
      daily hassles among unaccompanied refugees, and whether they might affect mental
      health of young refugees after resettlement. First, we examined the underlying
      structure of daily hassles conceptualized as measuring general and acculturation
      specific hassles. Second, we examined whether these two distinct categories of
      daily hassles significantly contribute to depression above and beyond the impact
      of premigration trauma. DESIGN: The study was based on self-report questionnaire
      data collected from 895 unaccompanied refugees who had been granted residence in
      Norway. RESULTS: Using structural equation modeling, the results confirmed the
      grouping of hassles in two general categories, which explained 43% of the
      variance in depression. CONCLUSION: The findings underscore the importance of
      current life conditions for unaccompanied refugees' mental health.

PMID- 26208790
TI  - Molecular insight into amyloid oligomer destabilizing mechanism of flavonoid
      derivative 2-(4' benzyloxyphenyl)-3-hydroxy-chromen-4-one through docking and
      molecular dynamics simulations.
AB  - Aggregation of amyloid peptide (Abeta) has been shown to be directly related to
      progression of Alzheimer's disease (AD). Abeta is neurotoxic and its deposition
      and aggregation ultimately lead to cell death. In our previous work, we reported
      flavonoid derivative (compound 1) showing promising result in transgenic AD model
      of Drosophila. Compound 1 showed prevention of Abeta-induced neurotoxicity and
      neuroprotective efficacy in Drosophila system. However, mechanism of action of
      compound 1 and its effect on the amyloid is not known. We therefore performed
      molecular docking and atomistic, explicit-solvent molecular dynamics simulations
      to investigate the process of Abeta interaction, inhibition, and destabilizing
      mechanism. Results showed different preferred binding sites of compound 1 and
      good affinity toward the target. Through the course of 35 ns molecular dynamics
      simulation, conformations_5 of compound 1 intercalates into the hydrophobic core
      near the salt bridge and showed major structural changes as compared to other
      conformations. Compound 1 showed interference with the salt bridge and thus
      reducing the inter strand hydrogen bound network. This minimizes the side chain
      interaction between the chains A-B leading to disorder in oligomer. Contact map
      analysis of amino acid residues between chains A and B also showed lesser
      interaction with adjacent amino acids in the presence of compound 1
      (conformations_5). The study provides an insight into how compound 1 interferes
      and disorders the Abeta peptide. These findings will further help to design
      better inhibitors for aggregation of the amyloid oligomer. 

PMID- 26208791
TI  - Examination of a recommended algorithm for eliminating nonsystematic delay
      discounting response sets.
AB  - PURPOSE: To examine (1) whether use of a recommended algorithm (Johnson and
      Bickel, 2008) improves upon conventional statistical model fit (R(2)) for
      identifying nonsystematic response sets in delay discounting (DD) data, (2)
      whether removing such data meaningfully effects research outcomes, and (3) to
      identify participant characteristics associated with nonsystematic response sets.
      METHODS: Discounting of hypothetical monetary rewards was assessed among 349
      pregnant women (231 smokers and 118 recent quitters) via a computerized task
      comparing $1000 at seven future time points with smaller values available
      immediately. Nonsystematic response sets were identified using the algorithm and
      conventional statistical model fit (R(2)). The association between DD and
      quitting was analyzed with and without nonsystematic response sets to examine
      whether the inclusion or exclusion impacts this relationship. Logistic regression
      was used to examine whether participant sociodemographics were associated with
      nonsystematic response sets. RESULTS: The algorithm excluded fewer cases than the
      R(2) method (14% vs. 16%), and was not correlated with logk as is R(2). The
      relationship between logk and the clinical outcome (spontaneous quitting) was
      unaffected by exclusion methods; however, other variables in the model were
      affected. Lower educational attainment and younger age were associated with
      nonsystematic response sets. CONCLUSIONS: The algorithm eliminated data that were
      inconsistent with the nature of discounting and retained data that were orderly.
      Neither method impacted the smoking/DD relationship in this data set.
      Nonsystematic response sets are more likely among younger and less educated
      participants, who may need extra training or support in DD studies.

PMID- 26208792
TI  - Individual and neighborhood predictors of mortality among HIV-positive Latinos
      with history of injection drug use, Florida, 2000-2011.
AB  - BACKGROUND: The objectives are to examine disparities in all-cause mortality risk
      among HIV-positive Latinos with injection drug use (IDU) history, and to identify
      individual- and neighborhood-level predictors. METHODS: Florida surveillance data
      for persons diagnosed with HIV 2000-2008 were merged with 2007-2011
      administrative data from the American Community Survey. Hazard ratios (HR) were
      calculated using multi-level weighted Cox regression adjusting for individual and
      neighborhood (ZCTA-level) factors. RESULTS: Of 10,989 HIV-positive Latinos, 10.3%
      had IDU history. Latinos with IDU history were at increased mortality risk
      compared with Latinos without IDU history after controlling for individual and
      neighborhood factors (adjusted HR [aHR] 1.61, 95% confidence interval [CI] 1.43
      1.80). Factors associated with mortality for those with IDU history included:
      being 40-59 (aHR 6.48, 95% CI 1.41-121.05) and >=60 years (aHR 18.75, 95% CI 3.83
      356.45) compared with 13-19 years of age; being diagnosed with AIDS within 3
      months of HIV (aHR 2.31, 95% CI 1.87-2.86); residing in an area with >=50%
      Latinos compared with <25% Latinos (aHR 1.56, 95% CI 1.19-2.04); and residing in
      a rural compared with an urban area at the time of diagnosis (aHR 1.73, 95% CI
      1.06-2.70). Race and neighborhood poverty were not predictors among those with
      IDU, but were among those without. CONCLUSION: HIV-positive Latinos with IDU
      history are at increased mortality risk and have unique contributing factors.
      Tertiary prevention strategies should target those who are older, diagnosed at
      later stages, and those who live in predominantly Latino and rural areas.

PMID- 26208793
TI  - Risk factors for concurrent use of benzodiazepines and opioids among individuals
      under community corrections supervision.
AB  - BACKGROUND: The use of heroin and prescription opioids has increased over the
      past decade. The concurrent use of opioids with other depressants such as
      benzodiazepines increases the risk of overdose death compared with use of either
      drug alone. This study examined factors associated with concurrent use of opioids
      and benzodiazepines in a criminal justice sample in the state of Alabama.
      METHODS: The Addiction Severity Index (ASI) and urine drug screen results from
      28,570 individuals who were under community corrections supervision from 2002
      2012 were examined for independent or concurrent opioid and benzodiazepine use.
      Multinomial logistic regression analyses were conducted to determine associations
      between socio-demographic characteristics and drug use. RESULTS: Concurrent use
      was detected in 11.5% of the sample. Concurrent use of opioids and
      benzodiazepines or use of either drug alone was associated with being White,
      female, married, prescribed psychiatric medications, having seen a physician in
      the past two years, cannabis use, and having a drug-related offense. Concurrent
      users were more likely to be unemployed or disabled and have received counseling,
      and less likely to have completed college, live with relatives or friends, have a
      history of hallucinations, or have an offense against a person relative to
      nonusers. DISCUSSION: While significant overlap of risk factors exists between
      individuals with concurrent use versus sole use of opioids or benzodiazepines,
      individuals with concurrent use generally have more social dysfunction than
      individuals who tested for either substance alone. Concurrent users may need more
      psychosocial resources and intensive treatments to promote recovery.

PMID- 26208794
TI  - Extensive mapping of an innate immune network with CRISPR.
AB  - The application of the CRISPR-Cas9 system marks a major breakthrough for genetic
      screens, particularly in mammalian cells where high-throughput targeted gene
      editing has been lacking. Parnas et al (2015) apply this screening technology to
      mouse bone marrow-derived dendritic cells in order to study the regulation of the
      immune response triggered by PAMPs. Through integrated analysis of gene knockouts
      in conjunction with changes in protein and mRNA expression, CRISPR screens are
      facilitating dissection of immune regulatory networks at unprecedented
      resolution.

PMID- 26208795
TI  - Impact of a cholesterol membrane transporter's inhibition on vitamin D
      absorption: A double-blind randomized placebo-controlled study.
AB  - Oral supplements are important to prevent and treat vitamin D deficiency. Despite
      the growing number of prescriptions, vitamin D's absorptive mechanisms are not
      clearly elucidated. By evaluating the effect of ezetimibe on vitamin D
      absorption, we aim to determine if the cholesterol transporter Niemann-Pick C1
      Like 1 transporter contributes to it. This randomized, double-blind, placebo
      controlled trial (ClinicalTrials.govNCT02234544) was developed in a South
      Brazilian University Hospital. Fifty-one medical students were randomized to
      ezetimibe 10mg/day or placebo for 5 days. On the fifth and 19th days, blood
      samples for 25-hydroxycholecalciferol (25OHD), parathyroid hormone (PTH),
      calcium, and albumin were collected. After the first blood sample collection, all
      participants received a single oral 50,000 IU cholecalciferol dose during a 15 g
      fat meal. Serum 25OHD levels were measured by the immunoassay Diasorin
      Liaison(r). Measurements were compared in a general linear model adjusted for
      multiple comparisons by the Bonferroni test. Before cholecalciferol
      administration, 25OHD was <30 ng/mL and <20 ng/mL, respectively, in all and in
      82.3% of the participants. Fourteen days after a single 50,000 IU oral dose of
      cholecalciferol, mean (SD) changes in serum 25OHD were similar in both groups,
      after adjustment to BMI and 25OHD levels before cholecalciferol administration
      (p=0.26): 8.7 (3.7) ng/mL in the ezetimibe group, versus 10.0 (3.8) ng/mL in the
      placebo group. Mean serum 25OHD, PTH, calcium and albumin levels remained similar
      in both groups. We conclude that ezetimibe had no effect on the mean change in
      serum 25OHD after a single oral dose of cholecalciferol, in these healthy and
      young adults.

PMID- 26208796
TI  - Decursin inhibits osteoclastogenesis by downregulating NFATc1 and blocking fusion
      of pre-osteoclasts.
AB  - Bone sustains its structure through dynamic interaction between osteoblastic
      cells and osteoclastic cells. But imbalance may lead to osteoporosis caused by
      overactivated osteoclast cells that have bone-resorbing function. Recently, herbs
      have been researched as major sources of medicines in many countries. In vitro
      and in vivo anti-osteoclastogenic activity of Angelica gigas NAKAI have been
      reported, but the biological activity of decursin, its major component in
      osteoclast differentiation is still unknown. Therefore, in this study, we
      explored whether decursin could affect RANKL-mediated osteoclastogenesis. The
      results showed that decursin efficiently inhibited RANKL-activated osteoclast
      differentiation by inhibiting transcriptional and translational expression of
      NFATc1, a major factor in RANKL-mediated osteoclastogenesis. Furthermore,
      decursin decreased fusion and migration of pre-osteoclasts by downregulating mRNA
      expression levels of DC-STAMP and beta3 integrin, respectively. In addition,
      decursin prevents lipopolysaccharide (LPS)-induced bone erosion in vivo. In
      summary, decursin could prevent osteoclastogenesis and inflammatory bone loss via
      blockage of NFATc1 activity and fusion and migration of pre-osteoclasts, and it
      could be developed as a potent phytochemical candidate for treating pathologies
      of bone diseases. 

PMID- 26208797
TI  - Mechanisms of enhanced osteoclastogenesis in girls and young women with Turner's
      Syndrome.
AB  - Subjects with hypergonadotropic hypogonadism due to Turner's syndrome show low
      cortical mineral density, osteoporosis and risk of fractures. It is not clear if
      this bone fragility derives from chromosomal abnormalities or is the result of
      inadequate bone formation due to estrogen deficiency. The aim of this study was
      to investigate the cellular mechanisms underlying bone fragility in subjects with
      Turner's syndrome before induction of puberty and after hormonal replacement
      therapy (HRT). For this purpose, we have evaluated the osteoclastogenic potential
      of non-fractioned and T-cell depleted cultures of peripheral blood mononuclear
      cells (PBMCs) belonging to girls with Turner's syndrome who had not been treated
      with HRT yet, girls and young women who were on HRT and age-matched controls.
      Untreated subjects showed high FSH serum levels, whereas the other subjects
      displayed normal FSH serum levels. T-cell immunophenotype was analyzed through
      flow cytometry. Biochemical and DXA analyses were performed. Spontaneous
      osteoclastogenesis in non-fractioned and T-cell depleted cultures of PBMC
      belonging to girls with high FSH levels was more evident than in cultures of
      subjects with normal FSH levels. In the former, osteoclastogenesis was sustained
      by monocytes expressing high levels of c-fms, TNF-alpha and RANK, and T-cells
      producing high RANKL and TNF-alpha; in the latter it was supported by T-cells
      expressing high RANKL levels. CD4(+)CD25(high) T-cells were reduced in all
      subjects, whereas CD3(+)/CD16(+)/CD56(+) NKT-cells were increased in those with
      high FSH levels. High RANKL and CTX levels were detected in the sera. Bone
      impairment was already detectable by DXA in subjects aged under 10, although it
      became more evident with aging. In conclusion, our results demonstrated that bone
      fragility in subjects with Turner's syndrome is associated to enhanced
      osteoclastogenesis. This process seems to be due to high FSH serum levels before
      HRT, whereas it is caused by high RANKL during HRT. 

PMID- 26208798
TI  - Mutational spectrum of the SPAST and ATL1 genes in Korean patients with
      hereditary spastic paraplegia.
AB  - Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of
      diseases characterized by insidiously progressive lower-extremity weakness and
      spasticity. Spastic paraplegia 4 (SPAST) is the most common type of uncomplicated
      autosomal dominant HSP (40% of such cases), and spastic paraplegia 3A (ATL1) is
      the second most common. Here, we conducted mutational analysis of the SPAST
      and/or ATL1 genes in 206 unrelated patients with HSP. DNA sequencing and
      multiplex ligation-dependent probe amplification was used to analyze SPAST or
      ATL1 pathogenic variants. To confirm splice-site pathogenic variants, mRNA
      transcripts were analyzed by reverse transcription-polymerase chain reactions and
      sequencing. Among the 52 patients with medical records and SPAST or ATL1 gene
      pathogenic variants or novel unclassified variants, 50 showed spasticity or
      weakness in their lower extremities. We identified 16 known and 18 novel SPAST
      pathogenic variants and 2 known and a novel splicing pathogenic variants in ATL1.
      We also identified 4 unclassified SPAST variants in 5 patients and an
      unclassified ATL1 variant in 1 patient. Further, a novel leaky-splicing variant
      (c.1537-11A>G) was found in SPAST, which caused skipping of exon 13 or exons 13
      14. Among the 206 unrelated patients with HSP, SPAST or ATL1 pathogenic variants
      and potentially pathogenic variants were identified in 52 patients, a low
      pathogenic variant rate compared to previous results. Results from our study
      suggest that other genes may be involved in HSP in the Korean population.

PMID- 26208799
TI  - High Angiopoietin-1 levels predict a good functional outcome within 72 h of an
      aneurysmal subarachnoid hemorrhage: A prospective study from a single center.
AB  - BACKGROUND: The consequences of aneurysmal subarachnoid hemorrhage (aSAH) are
      lifelong and fatal. Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) play an
      important role in the regulation of vascular structure and function. Our study
      examined the association between angiopoietin levels and functional outcomes
      among aSAH patients. METHODS: We enrolled 37 aSAH patients and 39 controls
      (matched on age and sex) at the Department of Neurosurgery in Tianjin Medical
      University General Hospital. Serum Ang-1, Ang-2, and Tie-2 levels were collected
      at 8, 24, and 72 hours post-hemorrhage. After a 3-month follow-up period, patient
      outcomes were evaluated using the Glasgow Outcome Score (GOS). Logistic
      regression examined the association between angiopoietin levels and outcomes
      (good [GOS: 4-5] vs. poor [GOS: 1-3]). RESULTS: aSAH patients had higher levels
      of Ang-1 at 8 hours post-hemorrhage compared to controls. Among aSAH patients,
      Ang-1 levels at 8, 24, and 72 hours post-hemorrhage were higher among patients
      with a good outcome. Compared to patients with low Ang-1 levels, high Ang-1
      levels at 72 hours post-hemorrhage were associated with a good outcome.
      CONCLUSIONS: High Ang-1 levels were associated with a good functional outcome
      after aSAH. Abnormal angiopoietin levels may disrupt the blood-brain barrier and
      contribute to functional outcomes in aSAH patients.

PMID- 26208800
TI  - (123)I-MIBG myocardial scintigraphy and neurocirculatory abnormalities in
      patients with dementia with Lewy bodies and Alzheimer's disease.
AB  - BACKGROUND: Although adoption of new clinical criteria for dementia with Lewy
      bodies (DLB) leads to an increase in the proportion of patients diagnosed with
      probable DLB, the sensitivity of clinical diagnostic criteria of DLB is low, and
      there are no generally accepted clinical or imaging biomarkers to distinguish DLB
      from other types of dementia. In this study, we investigated whether
      neurocirculatory abnormalities and cardiac sympathetic denervation differed in
      controls and patients with subjective memory impairment (SMI), mild cognitive
      impairment (MCI), Alzheimer's disease (AD), and DLB. We also assessed whether
      spontaneous features of Parkinsonism might be related to the neurocirculatory
      abnormalities and cardiac sympathetic denervation found in DLB. METHODS: Twenty
      two consecutive patients with probable DLB were enrolled in this study; 25 age
      matched controls, 14 SMI, 24 MCI, and 37 AD patients were also evaluated.
      Metaiodobenzylguanidine (MIBG) uptake was assessed using the ratio of the heart
      to the upper mediastinum (H/M ratio), and orthostatic vital signs and ambulatory
      24-hour blood pressure monitoring values were recorded. RESULTS: The mean H/M
      ratio was significantly lower and the proportion of orthostatic hypotension was
      higher in patients with DLB than in controls, SMI, MCI and AD patients. In
      patients with DLB, spontaneous Parkinsonism was not related to the degree of
      cardiac sympathetic denervation nor did it influence neurocirculatory
      abnormalities. CONCLUSION: Our results suggest that MIBG scintigraphy and
      autonomic function tests may be useful for distinguishing between DLB and AD in
      clinical practice. Myocardial postganglionic sympathetic denervation and
      autonomic dysfunctions are present in patients with DLB regardless of spontaneous
      Parkinsonism.

PMID- 26208801
TI  - Predictors associated with stroke after coronary artery bypass grafting: a
      systematic review.
AB  - BACKGROUND: Stroke is a major cause of morbidity and mortality after coronary
      artery bypass grafting (CABG). The purpose of this systematic review was to
      evaluate the predictors of perioperative stroke after CABG. METHODS: We reviewed
      the published literature on prognostic factors for perioperative stroke after
      CABG in articles using multivariate regression models. The statistical validity
      of prognostic models and a qualitative synthesis were performed. RESULTS: We
      identified 14 studies. The methodological quality of study reporting was
      variable. Overall, the incidence of stroke after CABG was 1.1-5.7%. About 37-59%
      of strokes occurred early (intraoperatively). No validated stroke outcome scale
      was used to assess morbidity and mortality in any of the included studies.
      Advanced age, prior (before CABG) cerebrovascular disease/stroke, prior carotid
      artery stenosis, prior peripheral vascular disease, prior unstable angina, and
      prolonged cardiopulmonary bypass time were found to be the most consistent
      independent predictors of perioperative stroke after CABG. Postoperative atrial
      fibrillations were found to be the most consistent independent variables
      associated with postoperative stroke after CABG. No association was found with
      hypercholesterolemia, prior myocardial infarct, and smoking. Other risk factors,
      such as gender, prior hypertension, diabetes mellitus, congestive heart failure,
      and chronic renal failure, showed inconsistent results. CONCLUSIONS: Seven
      variables (advanced age, prior cerebrovascular disease/stroke, prior carotid
      artery stenosis, prior peripheral vascular disease, prior unstable angina,
      prolonged cardiopulmonary bypass time, and postoperative atrial fibrillation),
      representing and high atherosclerotic burden, were found to be associated with
      more perioperative stroke events. Stroke assessment scales should be included to
      enable a detailed description of stroke morbidity post CABG. Lessons learned from
      the present study should also help to improve the quality and relevance of future
      studies on prognostic factors in stroke after CABG.

PMID- 26208802
TI  - Multidirectional Instability of the Shoulder: A Systematic Review.
AB  - PURPOSE: To analyze outcomes of surgical and conservative treatment options for
      multidirectional instability (MDI). METHODS: A systematic review of the
      literature according to the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) guidelines was performed. A comprehensive search of the
      PubMed, MEDLINE, CINAHL, Cochrane, EMBASE, and Google Scholar databases using
      various combinations of the keywords "shoulder," "multidirectional instability,"
      "dislocation," "inferior instability," "capsulorrhaphy," "capsular plication,"
      "capsular shift," "glenoid," "humeral head," "surgery," and "glenohumeral," over
      the years 1966 to 2014 was performed. RESULTS: Twenty-four articles describing
      patients with open capsular shift, arthroscopic treatment, and conservative or
      combined management in the setting of atraumatic MDI of the shoulder were
      included. A total of 861 shoulders in 790 patients was included. The median age
      was 24.3 years, ranging from 9 to 56 years. The dominant side was involved in 269
      (58%) of 468 shoulders, whereas the nondominant side was involved in 199 (42%)
      shoulders. Patients were assessed at a median follow-up period of 4.2 years
      (ranging from 9 months to 16 years). Fifty-two of 253 (21%) patients undergoing
      physiotherapy required surgical intervention for MDI management, whereas the
      overall occurrence of redislocation was seen in 61 of 608 (10%) shoulders
      undergoing surgical procedures. The redislocation event occurred in 17 of 226
      (7.5%) shoulders with open capsular shift management, in 21 of 268 (7.8%)
      shoulders with arthroscopic plication management, in 12 of 49 (24.5%) shoulders
      undergoing arthroscopic thermal shrinkage, and in 11 of 55 (22%) shoulders
      undergoing arthroscopic laser-assisted capsulorrhaphy. CONCLUSIONS: Arthroscopic
      capsular plication and open capsular shift are the best surgical procedures for
      treatment of MDI after failure of rehabilitative management. Arthroscopic
      capsular plication shows results comparable to open capsular shift. LEVEL OF
      EVIDENCE: Level IV, systematic review of Level I to IV studies.

PMID- 26208803
TI  - Genetic interactions between the Golgi Ca2+/H+ exchanger Gdt1 and the plasma
      membrane calcium channel Cch1/Mid1 in the regulation of calcium homeostasis,
      stress response and virulence in Candida albicans.
AB  - The Golgi-localized Saccharomyces cerevisiae ScGdt1 is a member of the
      cation/Ca(2+) exchanger superfamily. We show here that Candida albicans CaGdt1 is
      the functional homolog of ScGdt1 in calcium sensitivity, and shows genetic
      interactions with CaCch1 or CaMid1 in response to ER stresses. In addition,
      similar to ScCCH1 and ScMID1, deletion of either CaCCH1 or CaMID1 leads to a
      growth sensitivity of cells to cold stress, which can be suppressed by deletion
      of CaGDT1. Furthermore, deletion of CaCCH1 leads to a severe delay in
      filamentation of C. albicans cells, and this defect is abolished by deletion of
      CaGDT1. In contrast, CaGDT1 does not show genetic interaction with CaMID1 in
      filamentation. Interestingly, C. albicans cells lacking both CaMID1 and CaGDT1
      exhibit an intermediate virulence between C. albicans cells lacking CaCCH1 (non
      virulent) and C. albicans cells lacking CaGDT1 (partially virulent), while C.
      albicans cells lacking both CaCCH1 and CaGDT1 are not virulent in a mouse model
      of systemic candidiasis. Therefore, CaGdt1 genetically interacts with the plasma
      membrane calcium channel, CaCch1/CaMid1, in the response of C. albicans cells to
      cold and ER stresses and antifungal drug challenge as well as in filamentation
      and virulence. 

PMID- 26208804
TI  - The Co-chaperone BAG2 Mediates Cold-Induced Accumulation of Phosphorylated Tau in
      SH-SY5Y Cells.
AB  - Inclusions of phosphorylated tau (p-tau) are a hallmark of many neurodegenerative
      disorders classified as "tauopathy," of which Alzheimer's disease is the most
      prevalent form. Dysregulation of tau phosphorylation disrupts neuron structure
      and function, and hyperphosphorylated tau aggregates to form neurotoxic
      inclusions. The abundance of ubiquitin in tau inclusions suggests a defect in
      ubiquitin-mediated tau protein degradation by the proteasome. Under the
      temperature of 37  degrees C, the co-chaperone BAG2 protein targets
      phosphorylated tau for degradation via by a more-efficient, ubiquitin-independent
      pathway. In both in vivo and in vitro studies, cold exposure induces the
      accumulation of phosphorylated tau protein. The SH-SY5Y cell line differentiates
      into neuron-like cells on treatment with retinoic acid and is an established
      model for research on the effects of cold on tau phosphorylation. The aim of the
      present study was to investigate whether BAG2 mediates the cold-induced
      accumulation of phosphorylated tau protein. Our findings show that cold exposure
      causes a decrease in BAG2 expression in undifferentiated cells. Conversely, BAG2
      expression is increased in differentiated cells exposed to cold. Further,
      undifferentiated cells exposed to cold had an increased proportion of p-tau to
      total tau, suggesting an accumulation of p-tau that is consistent with decreased
      levels of BAG2. Overexpression of BAG2 in cold-exposed undifferentiated cells
      restored levels of p-tau to those of 37  degrees C undifferentiated control.
      Interestingly, although BAG2 expression increased in differentiated cells, this
      increase was not accompanied by a decrease in the proportion of p-tau to total
      tau. Further, overexpression of BAG2 in cold exposed differentiated cells showed
      no significant difference in p-tau levels compared to 37  degrees C controls.
      Taken together, these data show that expression of BAG2 is differently regulated
      in a differentiation-dependent context. Our results suggest that repression of
      BAG2 expression or BAG2 activity by cold-sensitive pathways, as modeled in
      undifferentiated and differentiated cells, respectively, may be a causal factor
      in the accumulation of cytotoxic hyperphosphorylated tau protein via restriction
      of BAG2-mediated clearance of cellular p-tau. 

PMID- 26208805
TI  - Serotonin Depletion Does not Modify the Short-Term Brain Hypometabolism and
      Hippocampal Neurodegeneration Induced by the Lithium-Pilocarpine Model of Status
      Epilepticus in Rats.
AB  - It has been reported that fluoxetine, a selective serotonin (5-hydroxytryptamine;
      5-HT) reuptake inhibitor, has neuroprotective properties in the lithium
      pilocarpine model of status epilepticus (SE) in rats. The aim of the present
      study was to investigate the effect of 5-HT depletion by short-term
      administration of p-chlorophenylalanine (PCPA), a specific tryptophan hydroxylase
      inhibitor, on the brain hypometabolism and neurodegeneration induced in the acute
      phase of this SE model. Our results show that 5-HT depletion did modify neither
      the brain basal metabolic activity nor the lithium-pilocarpine-induced
      hypometabolism when evaluated 3 days after the insult. In addition, hippocampal
      neurodegeneration and astrogliosis triggered by lithium-pilocarpine were not
      exacerbated by PCPA treatment. These findings point out that in the early latent
      phase of epileptogenesis, non-5-HT-mediated actions may contribute, at least in
      some extent, to the neuroprotective effects of fluoxetine in this model of SE. 

PMID- 26208806
TI  - Improving a Urine Culture Callback Follow-up System in a Pediatric Emergency
      Department.
AB  - INTRODUCTION: Delays in appropriate treatment and unnecessary antibiotic use for
      urinary tract infections (UTIs) increase the risk for serious adverse events and
      the potential for antibiotic resistance. The purposes of this quality improvement
      project were to decrease emergency department laboratory result follow-up time
      and increase the number of patients who are notified to stop taking an empiric
      antibiotic. METHOD: Nine months of Plan-Do-Study-Act (PDSA) cycles were
      implemented in a pediatric emergency department and network of care sites. Three
      months of baseline data were compared with 3 months of postinvention data using t
      tests and odds ratios. RESULTS: Time to patient/family laboratory follow-up was
      reduced from 20.1 hours to 7.1 hours, demonstrating a 64.7% reduction in time to
      follow-up (p < .01). The percentage of patients who received follow-up
      notification of negative urine cultures and were told to discontinue antibiotic
      therapy increased from 8.8% to 74.4% (p < .001). DISCUSSION: Implementation of a
      culture callback system, staffed by advanced practice providers, led to a
      significant reduction in the amount of time to follow-up and increased the number
      of follow-up calls to discontinue antibiotics when urine cultures were negative.

PMID- 26208807
TI  - Sex-age-specific association of body mass index with all-cause mortality among
      12.8 million Korean adults: a prospective cohort study.
AB  - BACKGROUND: Despite differences in body shape and adiposity characteristics
      according to sex and age, a single range of healthy weight [body mass index (BMI,
      kg/m(2)) of 18.5-24.9) regardless of sex and age has been recommended. The aim of
      the study is to examine whether the association between BMI and all-cause
      mortality varies by sex and age, and, if relevant, to estimate sex-age-specific
      optimal BMIs associated with a minimal risk of death. METHODS: A total of
      12,832,637 Korean adults aged 18-99 years who participated in health examinations
      during 2001-04 were followed up until 2013. Hazard ratios of death in sex-age
      groups were calculated using Cox regression models after adjustment for age,
      smoking status and known pre-existing illness. RESULTS: During follow-up, 456,175
      men and 241,208 women died. Among men, the age-specific optimal BMI was 23.0-25.9
      (kg/m(2)) at 18-34 years, 24.0-27.9 at 45-54 year, and 25.0-28.9 at 65-74 years.
      Among women, it was 15.5-24.9 at 18-34 years, 21.0-26.9 at 45-54 years and 24.0
      28.9 at 65-74 years. Patterns of sex-age-specific association generally did not
      differ between never-smokers with no known illness and all participants.
      Progressively increased risks above and below sex-age-specific optimums were
      observed (reverse J-curve). Smoking had a limited impact on the observed
      associations. CONCLUSIONS: Women had a lower optimal BMI than men, especially at
      younger ages. The optimal BMI increased with age. Change in optimal BMI with age,
      however, was more profound in women than in men. Sex-age-specific optimums were
      generally higher than the current normal weight (BMI of 18.5-24.9), except in
      women below 50 years. Sex-age-specific guidelines related to body weight may be
      needed to guide people for better health.

PMID- 26208808
TI  - [Successful ablation of an atrioventricular nodal reentrant tachycardia ablation
      2 years after orthotopic heart transplantation].
AB  - We report the case of a 48-year-old woman with an orthotopic heart
      transplantation. Two years after transplantation, the patient reported
      intermittent palpitations and dyspnea. The results of the 12-lead electrogram
      provided suspicion of AV nodal reentrant tachycardia (AVNRT), which was confirmed
      in the electrophysiological examination. The AVNRT was successfully eliminated
      without complications by radiofrequency catheter ablation of the slow pathway.
      The case shows that an AVNRT, even with existing sinus rhythm of the original
      heart, can also occur on the transplanted heart and ablation is safe and
      feasible. 

PMID- 26208809
TI  - Effects of topography on soil and litter mites (Acari: Oribatida, Mesostigmata)
      in a tropical monsoon forest in Southern Vietnam.
AB  - The effects of topographic variables (elevation above sea level, slope position,
      topographic (wetness) index, and global solar radiation) on mite abundances and
      on quantitative composition of Oribatida communities in soil and litter have been
      studied in six sites along a hill slope in a tropical lowland forest in the Bu
      Gia Map National Park, Southern Vietnam. A positive relationship existed between
      abundance and species richness of Oribatida in soil cores, and global solar
      radiation (W h m(-2)) which quantifies the total sun energy available to the
      local ecosystem. There was no significant relationship between abundance of
      Mesostigmata and topographic variables. The Oribatida community composition in
      soil and in litter was significantly different, with a large number of species
      unique to either litter or soil. The canonical correspondence analysis (CCA)
      showed that the topographic variables together explained 75% (in litter) and 83%
      (in soil) of the variation in Oribatida community structure. The species
      topography relationship was globally significant in the litter, weaker in the
      soil; the eigenvalue of the CCA axis 1 (related to elevation and global solar
      radiation) was significant in both substrates. CCA ordinations identified groups
      of species associated with high landscape positions (hill crest, high elevation,
      high global solar radiation) versus species associated with low-lying landscape
      positions, where moisture tends to accumulate (hill footslope, low elevation, low
      solar radiation, high topographic index values). The importance of relief and
      geographical position for soil Oribatida is discussed.

PMID- 26208810
TI  - Low Magnesium Levels in Adults with Metabolic Syndrome: a Meta-Analysis.
AB  - There is conflicting evidence regarding the relationship between magnesium
      deficiency and metabolic syndrome, and a systematic assessment of the literature
      has not been performed. Our objective was to clarify the association between
      magnesium levels and metabolic syndrome by performing a meta-analysis. Based on
      13 eligible studies involving 14 analyses and 5496 enrolled participants,
      magnesium levels were significantly lower in adults with metabolic syndrome than
      in controls (standardized mean difference [SMD] = -0.98, 95 % confidence interval
      [CI] = -1.44 to -0.52). There was marked heterogeneity when all comparisons were
      considered (I (2) = 98 %, p < 0.001). In the subgroup meta-analysis and meta
      regression model, a significant difference in magnesium levels was noted by
      geographic location and study quality. Magnesium levels were lower in the
      experimental cases than in the controls in West Asia (SMD = -3.80, 95 % CI = 
      5.36, -2.23) and Latin America (SMD = -1.38, 95 % CI = -1.88, -0.87), but not in
      East Asia (SMD = -0.01, 95 % CI = -0.30, 0.29) or Europe/Oceania (SMD = -0.25, 95
      % CI = -0.53, 0.03). Moreover, the inverse association was greater in high
      quality studies (SMD = -2.52, 95 % CI = -3.72, -1.32) than in low-quality studies
      (SMD = -0.33, 95 % CI = -0.57, -0.08). In conclusion, although there was a high
      level of heterogeneity, this meta-analysis provided convincing evidence of
      reduced magnesium levels in adults with metabolic syndrome based on the findings
      of observational studies. However, the present findings should be validated by
      additional prospective studies or trans-regional multicenter randomized
      controlled trials, which generally yield higher-level evidence than case-control
      studies and cross-sectional studies. CLINICAL TRIAL REGISTRATION NUMBER:
      NCT02151227 ( ClinicalTrials.gov Protocol Registration System); CRD42015017946 (
      www.crd.york.ac.uk/PROSPERO ).

PMID- 26208811
TI  - Mitochondrial oxidative stress-induced hepatocyte apoptosis reflects increased
      molybdenum intake in caprine.
AB  - Molybdenum (Mo) is an essential trace element for animals and humans. However,
      the high dietary intake of Mo leads to disease conditions in heavy metal
      pollution areas. To the best of our knowledge, the effect of high levels of Mo on
      the apoptosis of hepatocyte in goats has not been investigated. Therefore, the
      aim of the present in vivo study was to investigate the impact of Mo on
      mitochondrial oxidative stress and apoptosis genes in the liver using real-time
      quantitative polymerase chain reaction (RT-qPCR) and transmission electron
      microscopy, respectively. Thirty-six healthy goats were randomly divided into
      three groups: two groups treated with ammonium molybdate [(NH4)6.Mo7O24.H2O] at
      15 and 45 mg Mo kg(-1) BW, respectively, and a control group without treatment.
      Liver samples were collected from individual goats at different time intervals.
      The levels of oxidative stress in the mitochondrial membrane and expression of
      liver-related apoptosis genes, including Bcl-2, Cyt c, caspase-3, and Smac, were
      examined. The results demonstrated that the levels of superoxide dismutase (SOD)
      and catalase (CAT) expression were significantly down-regulated in liver cells,
      whereas malondialdehyde (MDA), nitric oxide (NO), and total nitric oxide synthase
      (T-NOS) expression was up-regulated (P < 0.01). The expression of Smac, Cyt c,
      and caspase-3 was significantly up-regulated, whereas Bcl-2 expression was down
      regulated in liver cells (P < 0.01). In addition, histopathological examination
      revealed varying degrees of vacuolization, irregularity, nuclear fission, and
      mitochondrial swelling and high-density electrons in the cytoplasm of hepatocytes
      in groups treated with 15 and 45 mg Mo kg(-1) BW. Thus, these results suggested
      that high molybdenum induced hepatocyte apoptosis and might involve a
      mitochondrial pathway. 

PMID- 26208813
TI  - A generalized item response tree model for psychological assessments.
AB  - A new item response theory (IRT) model with a tree structure has been introduced
      for modeling item response processes with a tree structure. In this paper, we
      present a generalized item response tree model with a flexible parametric form,
      dimensionality, and choice of covariates. The utilities of the model are
      demonstrated with two applications in psychological assessments for investigating
      Likert scale item responses and for modeling omitted item responses. The proposed
      model is estimated with the freely available R package flirt (Jeon et al.,
      2014b).

PMID- 26208814
TI  - Efficacy of methods for ovulation estimation and their effect on the statistical
      detection of ovulation-linked behavioral fluctuations.
AB  - Contention of the ovulatory shift hypothesis is principally supported by failures
      to replicate previous findings; e.g., recent meta-analytic work suggests that the
      effects endorsing the hypothesis may not be robust. Some possible limitations in
      this and other ovulatory-effects research-that may contribute to such controversy
      arising-are: (a) use of error-prone methods for assessing target periods of
      fertility that are thought to be associated with behavioral shifts, and (b) use
      of between-subjects-as opposed to within-subjects-methods. In the current study
      we present both simulated and empirical research: (a) comparing the ability of
      between- and within-subject t-tests to detect cyclical shifts; (b) evaluating the
      efficacy of correlating estimated fertility overlays with potential behavioral
      shifts; and (c) testing the accuracy of counting methods for identifying windows
      of cycle fertility. While this study cannot assess whether the ovulatory shift
      hypothesis or other ovulatory-based hypotheses are tenable, it demonstrates how
      low power resulting from typical methods employed in the extant literature may be
      associated with perceived inconsistencies in findings. We conclude that to fully
      address this issue greater use of within-subjects methodology is needed.

PMID- 26208812
TI  - Extrahepatic manifestations of hepatitis C infection: navigating CHASM.
AB  - This article describes the importance of extrahepatic systemic manifestations of
      chronic hepatitis C virus (HCV) infection. While most HCV literature focuses on
      liver injury and fibrosis progression, a spectrum of systemic disease processes,
      collectively called C hepatitis-associated systemic manifestations (CHASMs), are
      present in a high proportion of infected persons. These include thyroid disease
      (Hashimoto's thyroiditis, Graves disease, and thyroid cancer), cardiovascular
      disease (atherosclerosis, carotid artery disease, and coronary artery disease),
      renal disease (MPGN and glomerulosclerosis), eye disease (Mooren's ulcers and
      sicca syndrome), skin disease (PCT, vasculitis, and lichen planus), lymphomas
      (NHL and splenic T-cell), and diabetes. Mechanistic understanding of how HCV
      leads to CHASM processes could lead to development of new interventions. The role
      of early HCV treatment and cure may result in preventive strategies for a variety
      of complex disease states. Key Points * Systemic extrahepatic complications of
      HCV comprise a spectrum of disease states in many organs and systems.* Effective
      treatment of HCV may reduce or eliminate some but not all of these systemic
      complications.* Further research into early treatment intervention as a
      prevention strategy for systemic disease is warranted. 

PMID- 26208815
TI  - The ectomycorrhizal community of conifer stands on peat soils 12 years after
      fertilization with wood ash.
AB  - We studied long-term effects of fertilization with wood ash on biomass, vitality
      and mycorrhizal colonization of fine roots in three conifer forest stands growing
      in Vacciniosa turf. mel. (V), Myrtillosa turf. mel. (M) and Myrtillosa turf.
      mel./Caricoso-phragmitosa (MC) forest types on peat soils. Fertilization trials
      amounting 5 kg/m(2) of wood ash were established 12 years prior to this study. A
      total of 63 soil samples with roots were collected and analysed. Ectomycorrhizal
      (ECM) fungi in roots were identified by morphotyping and sequencing of the fungal
      internal transcribed spacer (ITS) region. In all forest types, fine root biomass
      was higher in fertilized plots than in control plots. In M forest type,
      proportion of living fine roots was greater in fertilized plots than in control
      plots, while in V and MC, the result was opposite. Fifty ECM species were
      identified, of which eight were common to both fertilized and control plots.
      Species richness and Shannon diversity index were generally higher in fertilized
      plots than in control plots. The most common species in fertilized plots were
      Amphinema byssoides (17.8%) and Tuber cf. anniae (12.2%), while in control plots,
      it was Tylospora asterophora (18.5%) and Lactarius tabidus (20.3%). Our results
      showed that forest fertilization with wood ash has long-lasting effect on
      diversity and composition of ECM fungal communities.

PMID- 26208816
TI  - Mycorrhization between Cistus ladanifer L. and Boletus edulis Bull is enhanced by
      the mycorrhiza helper bacteria Pseudomonas fluorescens Migula.
AB  - Boletus edulis Bull. is one of the most economically and gastronomically valuable
      fungi worldwide. Sporocarp production normally occurs when symbiotically
      associated with a number of tree species in stands over 40 years old, but it has
      also been reported in 3-year-old Cistus ladanifer L. shrubs. Efforts toward the
      domestication of B. edulis have thus focused on successfully generating C.
      ladanifer seedlings associated with B. edulis under controlled conditions.
      Microorganisms have an important role mediating mycorrhizal symbiosis, such as
      some bacteria species which enhance mycorrhiza formation (mycorrhiza helper
      bacteria). Thus, in this study, we explored the effect that mycorrhiza helper
      bacteria have on the efficiency and intensity of the ectomycorrhizal symbiosis
      between C. ladanifer and B. edulis. The aim of this work was to optimize an in
      vitro protocol for the mycorrhizal synthesis of B. edulis with C. ladanifer by
      testing the effects of fungal culture time and coinoculation with the helper
      bacteria Pseudomonas fluorescens Migula. The results confirmed successful
      mycorrhizal synthesis between C. ladanifer and B. edulis. Coinoculation of B.
      edulis with P. fluorescens doubled within-plant mycorrhization levels although it
      did not result in an increased number of seedlings colonized with B. edulis
      mycorrhizae. B. edulis mycelium culture time also increased mycorrhization levels
      but not the presence of mycorrhizae. These findings bring us closer to controlled
      B. edulis sporocarp production in plantations. 

PMID- 26208817
TI  - Comparing RECIST with EORTC criteria in metastatic bladder cancer.
AB  - OBJECTIVES: To compare RECIST and EORTC criteria in an evaluation of response to
      therapy in metastatic bladder cancer and to assess their influence on decisions
      to administer additional therapy. MATERIALS AND METHODS: A total of 42 untreated
      patients (38 male, 4 female) with metastatic bladder cancer were included in the
      study, which took place between July 2007 and April 2013. The mean age was 66.1
      +/- 9.93 years (range 41-84 years). A total of 144 metastatic foci were evaluated
      using multislice CT and (18)FDG-PET/CT before and after first-line chemotherapy.
      The locations, sizes, numbers and SUV(max) of the metastatic foci before and
      after chemotherapy were recorded, and the response to therapy was evaluated
      separately using RECIST and EORTC criteria, after which a statistical comparison
      was made. RESULTS: According to the RECIST and EORTC criteria, the rate of
      complete remission (CR) was 9.5 and 16.6 %, the rate of partial remission (PR)
      was 28.6 and 40.5 %, the rate of stable disease (SD) was 23.8 and 14.3 %, and the
      rate of progressive disease (PD) was 31.0 and 28.6 %, respectively. The overall
      response rate (ORR) was 38.1 versus 57.1 %, respectively, and there were no
      differences between the two criteria in terms of their detection of progressive
      disease. The rate of SD was higher with RECIST criteria; however, the difference
      between the two criteria was not significant in terms of PR and CR. CONCLUSION: A
      group of patients that had been determined as having a SD according to RECIST
      criteria were grouped as PR and/or CR according to EORTC criteria. Additional
      chemotherapy protocols can be used in second-line chemotherapy and/or cisplatin
      resistant patients, according to RECIST criteria. In evaluating the response to
      first-line chemotherapy for metastatic bladder cancer, EORTC criteria, using
      (18)FDG-PET/CT scans, can be considered as a more applicable and accurate
      diagnostic tool. The anatomical findings obtained through imaging methods and
      from functional/metabolic data obtained by PET/CT can be useful in the planning
      of second- or third-line chemotherapy, and a high accuracy in re-staging can
      spare patients from second-line or even third-line chemotherapy.

PMID- 26208818
TI  - Pediatric trauma care with computed tomography--criteria for CT scanning.
AB  - Trauma centers, trauma management concepts, as well as integration of whole-body
      computed tomography (CT) reduced mortality significantly. The accuracy of a
      trauma care algorithm with emergency CT in children was evaluated. Data of 71
      children with emergency CT were recorded retrospectively. In addition to
      epidemiological data admission date, kind of CT scan, mechanism of injury, missed
      diagnoses, injury severity score (ISS), admission to and time on intensive care
      unit (ICU), and time of hospitalization were observed. The algorithm for CT
      scanning was based on mechanism of injury, pattern of injury, and altered vital
      signs. Sixty-nine percent of the children reached the ER during on-call service
      hours. A percentage of 32.4 received a whole-body scan and 67.6 % a cranial scan.
      The mean ER ISS was 9.9 points (1-57). Children have different trauma mechanisms
      compared to adults. A percentage of 33.8 of the children had relevant trauma
      related findings in the CT scan. In 2 children, (2.8 %) 3 diagnoses (2.2 %) were
      initially missed. After reevaluation of the CT data, all diagnoses were
      identified. Thus, the accuracy of our algorithm in children was 100 %. In
      children, our algorithm detected all injuries, but only one third of the children
      had relevant trauma related findings in the CT scan. In order to reduce radiation
      exposure but preserve the advantages of CT, a new algorithm was developed with
      more flexibility taking the child's age and mental status more into account as
      well as clinical findings. The mechanism of injury itself is not anymore an
      indication for CT scanning.

PMID- 26208821
TI  - The 12th World Congress on Inflammation : 8-12 August, 2015 Seaport Hotel and
      World Trade Center, Boston, USA.

PMID- 26208819
TI  - Aligning to the sample-specific reference sequence to optimize the accuracy of
      next-generation sequencing analysis for hepatitis B virus.
AB  - BACKGROUND: Hepatitis B virus (HBV) quasispecies are crucial in the pathogenesis
      of chronic liver disease. Next-generation sequencing (NGS) is powerful for
      identifying viral quasispecies. To improve mapping quality and single nucleotide
      variant (SNV) calling accuracy in the NGS analysis of HBV, we compared different
      mapping references, including the sample-specific reference sequence, same
      genotype sequences and different genotype sequences, according to the sample.
      METHODS: Real Illumina HBV datasets from 86 patients, and simulated datasets from
      158 HBV strains in the GenBank database, were used to assess mapping quality. SNV
      calling accuracy was evaluated using different mapping references to align Real
      Illumina datasets from a single HBV clone. RESULTS: Using the sample-specific
      reference sequence as a mapping reference produced the largest number of mappable
      reads and coverages. With a different genotype mapping reference, the consensus
      sequence derived from the Real Illumina datasets of the single HBV clone showed
      21 false SNV callings in polymerase and surface genes, the regions most divergent
      between the mapping reference and this HBV clone. A ~6 % coverage of most of
      these false SNVs was yielded even with a same genotype mapping reference, but
      none with the sample-specific reference sequence. CONCLUSIONS: Using sample
      specific reference sequences as a mapping reference in NGS analysis optimized
      mapping quality and the SNV calling accuracy for HBV quasispecies.

PMID- 26208820
TI  - Association of the Laennec staging system with degree of cirrhosis, clinical
      stage and liver function.
AB  - OBJECTIVES: The aim of this study was to investigate the association of the
      Laennec staging system with degree of cirrhosis, clinical stage and liver
      function. METHODS: Liver biopsy was performed for 30 patients with hepatitis B
      cirrhosis to test the content of hydroxyproline in hepatic tissue, judge the
      degree of cirrhosis and determine the Laennec staging system. The association of
      the Laennec staging system with the degree of cirrhosis, clinical stage and liver
      function was compared. RESULTS: The Laennec staging system had a close
      association with clinical stage, model for end-stage liver disease score and
      degree of cirrhosis (r = 0.58, p < 0.01; r = 0.60, p < 0.01; r = 0.53, p < 0.01).
      CONCLUSIONS: The Laennec histological grading system can to some extent reflect
      the degree of cirrhosis, clinical stage and liver function, and is expected to
      predict the incidence of patient complications in a useful way.

PMID- 26208822
TI  - Odontoblast beta-catenin signaling regulates fenestration of mouse Hertwig's
      epithelial root sheath.
AB  - The interaction between Hertwig's epithelial root sheath (HERS) and the adjacent
      mesenchyme is vitally important in mouse tooth root development. We previously
      generated odontoblast-specific Ctnnb1 (encoding beta-catenin) deletion mice, and
      demonstrated that odontoblast beta-catenin signaling regulates odontoblast
      proliferation and differentiation. However, the role of odontoblast beta-catenin
      signaling in regulation of HERS behavior has not been fully investigated. Here,
      using the same odontoblast- specific Ctnnb1 deletion mice, we found that ablation
      of beta-catenin signaling in odontoblasts led to aberrant HERS formation.
      Mechanistically, odontoblast-specific Ctnnb1 deletion resulted in elevated bone
      morphogenetic protein 7 (Bmp7) expression and reduced expression of noggin and
      follistatin, both of which encode extracellular inhibitors of BMPs. Furthermore,
      the levels of phosphorylated Smad1/5/8 were increased in HERS cells. In vitro
      tissue culture confirmed that BMP7 treatment disrupted the HERS structure. Taken
      together, we demonstrated that odontoblast beta-catenin signaling may act through
      regulation of BMP signaling to maintain the integrity of HERS cells. 

PMID- 26208824
TI  - Insights into the function of tegument proteins from the varicella zoster virus.
AB  - Chickenpox (varicella) is caused by primary infection with varicella zoster virus
      (VZV), which can establish long-term latency in the host ganglion. Once
      reactivated, the virus can cause shingles (zoster) in the host. VZV has a typical
      herpesvirus virion structure consisting of an inner DNA core, a capsid, a
      tegument, and an outer envelope. The tegument is an amorphous layer enclosed
      between the nucleocapsid and the envelope, which contains a variety of proteins.
      However, the types and functions of VZV tegument proteins have not yet been
      completely determined. In this review, we describe the current knowledge on the
      multiple roles played by VZV tegument proteins during viral infection. Moreover,
      we discuss the VZV tegument protein-protein interactions and their impact on
      viral tissue tropism in SCID-hu mice. This will help us develop a better
      understanding of how the tegument proteins aid viral DNA replication, evasion of
      host immune response, and pathogenesis. 

PMID- 26208823
TI  - New insights into autocrine cytokines produced by ischemic cardiomyocytes and
      ventricular remodeling.

PMID- 26208825
TI  - Tea consumption reduces the incidence of gallbladder cancer based on a meta
      analysis of epidemiologic studies.

PMID- 26208826
TI  - Growth phase dependent changes in the structure and protein composition of
      nucleoid in Escherichia coli.
AB  - The genomic DNA of bacteria is highly compacted in a single or a few bodies known
      as nucleoids. Here, we have isolated Escherichia coli nucleoid by sucrose density
      gradient centrifugation. The sedimentation rates, structures as well as protein/
      DNA composition of isolated nucleoids were then compared under various growth
      phases. The nucleoid structures were found to undergo changes during the cell
      growth; i. e., the nucleoid structure in the stationary phase was more tightly
      compacted than that in the exponential phase. In addition to factor for inversion
      stimulation (Fis), histone-like nucleoid structuring protein (H-NS), heat
      unstable nucleoid protein (HU) and integration host factor (IHF) here we have
      identified, three new candidates of E. coli nucleoid, namely DNA-binding protein
      from starved cells (Dps), host factor for phage Qbeta (Hfq) and suppressor of td(
      ) phenotype A (StpA). Our results reveal that the major components of exponential
      phase nucleoid are Fis, HU, H-NS, StpA and Hfq, while Dps occupies more than half
      of the stationary phase nucleoid. It has been known for a while that Dps is the
      main nucleoid-associated protein at stationary phase. From these results and the
      prevailing information, we propose a model for growth phase dependent changes in
      the structure and protein composition of nucleoid in E. coli.

PMID- 26208827
TI  - SIRT5, functions in cellular metabolism with a multiple enzymatic activities.

PMID- 26208828
TI  - Primary leiomyosarcoma of the colon.
AB  - Primary leiomyosarcomas of the gastrointestinal (GI) tract are extremely rare and
      highly aggressive neoplasms, and only a small number of true cases have been
      reported since the concept of GI stromal tumors was established. Here, we report
      a case of a primary leiomyosarcoma of the transverse colon. A 46-year-old
      Japanese male with a large mass in the right upper abdomen was admitted to our
      hospital. Computed tomography and magnetic resonance imaging revealed long
      segments of wall thickening of the transverse colon with large consecutive tumors
      measuring 12 cm in diameter. A projecting irregular mass with marked mucosal
      necrosis was found on colonoscopy. Pathological examination revealed a spindle
      cell tumor growing circumferentially and transmurally to replace the muscularis
      propria in the transverse colon. The spindle cells were positive for smooth
      muscle actin, and negative for KIT, CD34, DOG-1, and S-100 protein. The patient
      has shown repeat recurrence in spite of sufficient surgical excision being
      promptly performed. 

PMID- 26208829
TI  - Lower Psychological Well-Being and Excessive Sexual Interest Predict Symptoms of
      Compulsive Use of Sexually Explicit Internet Material Among Adolescent Boys.
AB  - Although a growing body of literature addresses the effects of young people's use
      of sexually explicit Internet material, research on the compulsive use of this
      type of online content among adolescents and its associated factors is largely
      lacking. This study investigated whether factors from three distinct psychosocial
      domains (i.e., psychological well-being, sexual interests/behaviors, and
      impulsive-psychopathic personality) predicted symptoms of compulsive use of
      sexually explicit Internet material among adolescent boys. Links between
      psychosocial factors and boys' compulsive use symptoms were analyzed both cross
      sectionally and longitudinally with compulsive use symptoms measured 6 months
      later (T2). Data were used from 331 Dutch boys (M age = 15.16 years, range 11-17)
      who indicated that they used sexually explicit Internet material. The results
      from negative binomial regression analyses indicated that lower levels of global
      self-esteem and higher levels of excessive sexual interest concurrently predicted
      boys' symptoms of compulsive use of sexually explicit Internet material.
      Longitudinally, higher levels of depressive feelings and, again, excessive sexual
      interest predicted relative increases in compulsive use symptoms 6 months later.
      Impulsive and psychopathic personality traits were not uniquely related to boys'
      symptoms of compulsive use of sexually explicit Internet material. Our findings,
      while preliminary, suggest that both psychological well-being factors and sexual
      interests/behaviors are involved in the development of compulsive use of sexually
      explicit Internet material among adolescent boys. Such knowledge is important for
      prevention and intervention efforts that target the needs of specific problematic
      users of sexually explicit Internet material.

PMID- 26208830
TI  - Why Can't I Be More Like My Brother? The Role and Correlates of Sibling Social
      Comparison Orientation.
AB  - Siblings play an important role in relational and individual development
      throughout adolescence and beyond through several mechanisms. Central to this
      role and the mechanisms of sibling influence is the notion that siblings provide
      a constant and meaningful frame of reference for social comparison. This study
      examined the role of sibling social comparison orientation, or the tendency of
      siblings to compare themselves to one another, on youths' depressive symptoms and
      family relationships, both directly and by moderating links with parental
      differential treatment. Participants included 338 youth (M age = 18.34, SD =
      1.03; 52 % female). Using hierarchical ordinary least squares regression, we
      found that a higher sibling social comparison orientation was linked with more
      depressive symptoms, warmer sibling relationships, and more sibling conflict.
      Additionally, sibling social comparison orientation moderated links of parental
      differential treatment with depressive symptoms and prosocial behavior toward
      family members such that effects were more salient for those with a high
      comparison orientation. The discussion focuses on the role of sibling comparison
      in the ways that siblings influence one another's development. 

PMID- 26208831
TI  - From Family Violence to Dating Violence: Testing a Dual Pathway Model.
AB  - Risk factors for adolescent perpetration of or victimization by dating violence
      stem from different levels of adolescents' social ecologies, including the
      family, individual, and peer domains. However, these multiple risk factors have
      not been fully integrated into a single comprehensive model of dating violence
      development. The present study examined prospective links between exposure to
      family violence in pre-adolescence; pro-violent beliefs, aggression, deviant peer
      affiliation, and aggression toward opposite-sex peers in early adolescence and
      dating violence in late adolescence. Using a longitudinal study of 461 youth (51
      % female; 80 % African American, 19 % Caucasian, 1 % other ethnicities), path
      modeling evaluated a theoretically developed dual pathway model involving a
      general violence pathway and an early romantic aggression pathway. Each pathway
      links exposure to family violence in pre-adolescence with early adolescent pro
      violent beliefs and/or aggressive behavior. In both pathways, pro-violent beliefs
      may reinforce aggressive behaviors between same-sex and opposite-sex peers, as
      well as strengthen bonds with deviant peers. In the last part of both pathways,
      aggressive behavior and peer deviance in early adolescence may contribute
      directly to late adolescent dating violence perpetration and victimization. The
      findings provided support for both pathways, as well as sex differences in the
      model. 

PMID- 26208833
TI  - Evaluating automatic attentional capture by self-relevant information.
AB  - Our everyday decisions and memories are inadvertently influenced by self-relevant
      information. For example, we are faster and more accurate at making perceptual
      judgments about stimuli associated with ourselves, such as our own face or name,
      as compared with familiar non-self-relevant stimuli. Humphreys and Sui propose a
      "self-attention network" to account for these effects, wherein self-relevant
      stimuli automatically capture our attention and subsequently enhance the
      perceptual processing of self-relevant information. We propose that the masked
      priming paradigm and continuous flash suppression represent two ways to
      experimentally examine these controversial claims. 

PMID- 26208832
TI  - Parental Knowledge is a Contextual Amplifier of Associations of Pubertal
      Maturation and Substance Use.
AB  - Earlier pubertal development and less parental knowledge have been linked to more
      substance use during adolescence. The present study examines interactions between
      pubertal timing and tempo and parental knowledge (children's disclosure, parental
      control, and parental solicitation) for adolescent substance initiation. Data are
      from a northeastern US-based cohort-sequential study examining 1023 youth (52 %
      female) semiannually for up to 6 assessments (ages 10.5-19 years). The findings
      supported the hypothesis that lower knowledge is a contextual amplifier of early
      timing-substance use associations in girls and later timing/slower tempo
      substance use associations in boys, though results varied based on source of
      knowledge. The findings suggest that prevention efforts may have the greatest
      impact when targeting families of early developing girls, and later developing
      boys, and that incorporating a focus on specific sources of knowledge depending
      on the pubertal maturation profile of the adolescent may prove valuable in
      prevention/intervention efforts. 

PMID- 26208834
TI  - The social mysteries of the superior temporal sulcus.
AB  - The superior temporal sulcus (STS) is implicated in a variety of social
      processes, ranging from language perception to simulating the mental processes of
      others (theory of mind). In a new study, Deen and colleagues use functional
      magnetic resonance imaging (fMRI) to show a regular anterior-posterior
      organization in the STS for different social tasks. 

PMID- 26208835
TI  - CyberKnife Stereotactic Ablative Radiotherapy as an Option of Treatment for
      Patients With Prostate Cancer Having Oligometastatic Lymph Nodes: Single-Center
      Study Outcome Evaluation.
AB  - The aim of this study was to evaluate the effectiveness of CyberKnife-based
      stereotactic ablative radiotherapy on prostate cancer lymph node metastases. Our
      material consisted of 18 patients with 31 metastatic lymph nodes irradiated
      between 2011 and 2014 using CyberKnife-based stereotactic ablative radiotherapy.
      Patients were irradiated using fraction dose varied from 6 to 15 Gy (median 10),
      to the total dose of 24 to 45 Gy (median 30). Irradiated lymph node size varied
      from 0.4 to 4.0 cm. In all, 9 patients had single lymph node metastasis and 9
      patients had metastases of 2 to 4 lymph nodes. Prostate-specific antigen
      concentration before radiotherapy varied from 0.01 to 15.58 (mean 6.97; median
      4.66). All patients at the time of radiotherapy and follow-up received androgen
      deprivation therapy. Mann-Whitney U, Kaplan-Meier method, and log-rank tests were
      used in statistical analysis. We obtained the following results: after CyberKnife
      stereotactic ablative radiotherapy, prostate-specific antigen concentration
      dropped in majority of cases and during the last control varied from 0.00 to
      258.00 (median 2.5), and was lower in patients without dissemination to other
      organs (P = .01). Complete regression was found in 12 lesions, stable disease in
      13, and progression in 4. In 7 patients, the dissemination to other organs
      occurred. Our results allow us to conclude that CyberKnife stereotactic ablative
      radiotherapy of prostate cancer lymph node oligometastases gives good local
      control and relatively good prostate-specific antigen response.

PMID- 26208836
TI  - Spectral Imaging Technology-Based Evaluation of Radiation Treatment Planning to
      Remove Contrast Agent Artifacts.
AB  - OBJECTIVE: This study employs dual-source computed tomography single-spectrum
      imaging to evaluate the effects of contrast agent artifact removal and the
      computational accuracy of radiotherapy treatment planning improvement. METHOD:
      The phantom, including the contrast agent, was used in all experiments. The
      amounts of iodine in the contrast agent were 30, 15, 7.5, and 0.75 g/100 mL. Two
      images with different energy values were scanned and captured using dual-source
      computed tomography (80 and 140 kV). To obtain a fused image, 2 groups of images
      were processed using single-energy spectrum imaging technology. The Pinnacle
      planning system was used to measure the computed tomography values of the
      contrast agent and the surrounding phantom tissue. The difference between
      radiotherapy treatment planning based on 80 kV, 140 kV, and energy spectrum image
      was analyzed. RESULTS: For the image with high iodine concentration, the quality
      of the energy spectrum-fused image was the highest, followed by that of the 140
      kV image. That of the 80-kV image was the worst. The difference in the
      radiotherapy treatment results among the 3 models was significant. When the
      concentration of iodine was 30 g/100 mL and the distance from the contrast agent
      at the dose measurement point was 1 cm, the deviation values (P) were 5.95% and
      2.20% when image treatment planning was based on 80 and 140 kV, respectively.
      When the concentration of iodine was 15 g/100 mL, deviation values (P) were 
      2.64% and -1.69%. CONCLUSION: Dual-source computed tomography single-energy
      spectral imaging technology can remove contrast agent artifacts to improve the
      calculated dose accuracy in radiotherapy treatment planning.

PMID- 26208837
TI  - Fractionated Lung IMPT Treatments: Sensitivity to Setup Uncertainties and Motion
      Effects Based on Single-Field Homogeneity.
AB  - Treatment uncertainties in radiotherapy are either systematic or random. This
      study evaluates the sensitivity of fractionated intensity-modulated proton
      therapy (IMPT) lung treatments to systematic and random setup uncertainties.
      Treatments in which single-field homogeneity was restricted to within +/-20%
      (IMPT20%) were compared to full IMPT (IMPTfull) for 10 patients with lung cancer.
      Four-dimensional Monte Carlo calculations were performed using patient computed
      tomography geometries with +/-5 mm systematic or random setup uncertainties
      applied over a 35 * 2.5Gy(RBE) treatment course. Fifty fractionated courses were
      simulated for each patient using both IMPT delivery methods with random setup
      uncertainties applied each fraction and for 3 energy-dependent spot sizes (big
      spots, sigma~18-9 mm; intermediate spots, sigma~11-5 mm; and small spots, sigma~4
      2 mm). These results were compared to Monte Carlo recalculations of the original
      treatment plan assuming zero setup uncertainty. Results are presented as the
      difference in equivalent uniform dose (DeltaEUD), V95 (DeltaV95), and target dose
      homogeneity (DeltaD1-D99). Over the whole patient cohort, the DeltaEUD was 2.0 +/
      0.5 (big spots), 1.9 +/- 0.7 (intermediate spots), and 1.3 +/- 0.4 (small spots)
      times more sensitive to +/-5 mm systematic setup uncertainties in IMPTfull
      compared to IMPT20% IMPTfull is 1.9 +/- 0.9 (big spots), 2.1 +/- 1.1
      (intermediate spots), and 1.5 +/- 0.6 (small spots) times more sensitive to
      random setup uncertainties than IMPT20% over a fractionated treatment course. The
      DeltaV95 is at least 1.4 times more sensitive to systematic and random setup
      uncertainties for IMPTfull for all spot sizes considered. The DeltaD1-D99 values
      coincided within uncertainty limits for both IMPT delivery methods for the 3 spot
      sizes considered, with higher mean values always observed for IMPTfull The paired
      t-test indicated that variations observed between IMPTfull and IMPT20% were
      significantly different for the majority of scenarios. Significantly larger
      variations were observed in DeltaEUD and DeltaV95 in IMPTfull lung treatments in
      addition to higher mean DeltaD1-D99 The steep intra-target dose gradients in
      IMPTfull make it more susceptible to systematic and random setup uncertainties.

PMID- 26208838
TI  - When distance matters: Perceptual bias and behavioral response for approaching
      sounds in peripersonal and extrapersonal space.
AB  - Studies on sound perception show a tendency to overestimate the distance of an
      approaching sound source, leading to a faster reaction time compared to a
      receding sound source. Nevertheless, it is unclear whether motor preparation and
      execution change according to the perceived sound direction and distance,
      particularly when the sound falls inside the individual's peripersonal space. In
      this study we developed several auditory stimuli by means of two speakers,
      generating sounds moving toward the perceiver but stopping at different distances
      from her/him. Participants were asked to raise their arms as soon as the sound
      stopped, and their premotor and motor movement components were recorded by means
      of electromyography (EMG). Error in locating the perceived sound distance was
      also measured by asking participants to walk to the point in space where they
      believed the sound had stopped. Results showed that action initiation was
      anticipated as a function of sound distance: the closer the sound, the earlier
      the movement onset, when the sound entered the subject's peripersonal space. Less
      error for distance estimation was present when the sound was inside the
      peripersonal space with a modulation in the order of a few centimeters. Overall,
      our results reveal a link between perceptual bias in sound distance evaluation
      and peripersonal space, suggesting the presence of motor plan specificity. 

PMID- 26208840
TI  - The auditory space in the motor system.
AB  - Sensory events in the space around us trigger specific motor patterns directed
      toward or away from the spatial location of the sensory source. Spatially-defined
      sensorimotor associations are well-known in the visual domain but less so for the
      auditory modality. In particular no spatially-directed audio-motor association
      has been described for the upper limb. We tested the instantaneous directional
      tuning of the corticospinal system by means of single-pulse transcranial magnetic
      stimulation (TMS) over the left motor cortex in 16 healthy volunteers while at
      rest. We recorded the lateral accelerations of the TMS-evoked movement by means
      of an accelerometer placed on the forearm. Acoustic stimuli (pure tone
      frequency=1000Hz, duration=50ms) coming from 25 different directions lying in the
      axial anterior half-plane at the height of the participant's ears were played on
      earphones. The entire set of sound directions covered a span of 160 degrees  (+/
      80 degrees  where 0 degrees  is the frontal direction) at a fixed azimuth angle.
      Six different intervals between sound onset and TMS (0, 25, 50, 100, 150 and
      200ms) were tested for each sound direction. Significant correlations were found
      between sound origin and TMS-evoked arm accelerations only when TMS was delivered
      50ms prior to sound onset. We show the presence in the upper limb motor system of
      auditory spatial tuning. Sound information accesses the motor system at very
      short latency, potentially compatible with both a subcortical and a cortical
      origin of the response. The use of TMS-evoked accelerations allowed us to
      disclose a strict directional tuning in audio-motor associations. 

PMID- 26208839
TI  - Differential cerebellar GABAA receptor expression in mice with mutations in
      CaV2.1 (P/Q-type) calcium channels.
AB  - Ataxia is the predominant clinical manifestation of cerebellar dysfunction.
      Mutations in the human CACNA1A gene, encoding the pore-forming alpha1 subunit of
      CaV2.1 (P/Q-type) calcium channels, underlie several neurological disorders,
      including Episodic Ataxia type 2 and Familial Hemiplegic Migraine type 1 (FHM1).
      Several mouse mutants exist that harbor mutations in the orthologous Cacna1a
      gene. The spontaneous Cacna1a mutants Rolling Nagoya (tg(rol)), Tottering (tg)
      and Leaner (tg(ln)) mice exhibit behavioral motor phenotypes, including ataxia.
      Transgenic knock-in (KI) mouse strains with the human FHM1 R192Q and S218L
      missense mutations have been generated. R192Q KI mice are non-ataxic, whereas
      S218L KI mice display a complex behavioral phenotype that includes cerebellar
      ataxia. Given the dependence of gamma-aminobutyric acid type A (GABAA) receptor
      subunit functioning on localized calcium currents, and the functional link
      between GABAergic inhibition and ataxia, we hypothesized that cerebellar GABAA
      receptor expression is differentially affected in Cacna1a mutants and contributes
      to the ataxic phenotype. Herein we quantified functional GABAA receptors and
      pharmacologically dissociated cerebellar GABAA receptors in several Cacna1a
      mutants. We did not identify differences in the expression of GABAA receptor
      subunits or in the number of functional GABAA receptors in the non-ataxic R192Q
      KI strain. In contrast, tg(rol) mice had a ~15% decrease in the number of
      functional GABAA receptors, whereas S218L KI mice showed a ~29% increase. Our
      data suggest that differential changes in cerebellar GABAA receptor expression
      profile may contribute to the neurological phenotype of cerebellar ataxia and
      that targeting GABAA receptors might represent a feasible complementary strategy
      to treat cerebellar ataxia. 

PMID- 26208841
TI  - Compensatory projections of primary sensory fibers in lumbar spinal cord after
      neonatal thoracic spinal transection in rats.
AB  - Complete spinal transection in adult rats results in poor recovery of hind limb
      function, whereas significant spontaneous recovery can occur following spinal
      cord transection in rat neonates. The mechanisms underlying the recovery,
      however, are poorly understood. Recent studies in rodents suggested that the
      recovery is not due to axonal regeneration, but rather due to reorganization of
      the neural circuits in the spinal cord below the injury site, including central
      pattern generators. Few studies have reported histological evidence for changes
      in the primary sensory fibers or terminals. Thus, in the present study, we
      transected spinal cords of rats at thoracic level 8 at postnatal day 5. Four
      weeks after the injury, biotinylated-dextran amine (BDA), an anterograde tracer,
      was injected into the dorsal root ganglion of the lumbar spinal cord to examine
      the localization of sensory fibers and their terminal buttons in the spinal cord.
      BDA-positive axons in the rat spinal cord following neonatal spinal transection
      (neo ST) were longer than those in sham-operated or normal rats. The number of
      terminal buttons was also higher in spinal cords of neo ST rats compared with
      sham-operated or normal rats. These findings suggest that sensory fibers project
      more strongly and make more synapses following neo ST to compensate for the lack
      of supraspinal projections. 

PMID- 26208842
TI  - Functional differences in face processing between the amygdala and ventrolateral
      prefrontal cortex in monkeys.
AB  - The ability to categorize social information is essential to survive in a
      primate's social group. In the monkey brain, there are neural systems to
      categorize social information. Among these, the relationship between the amygdala
      and the ventrolateral prefrontal cortex (vlPFC) has recently gained focus with
      regard to emotion regulation. However, the processing of facial information and
      the functional differences in these two areas remain unclear. Thus, in this
      study, we examined the response properties of single neurons in the amygdala and
      vlPFC while presenting video clips of three types of facial emotions (aggressive
      threat, coo, and scream) in Macaca mulatta. Neurons in the amygdala were
      preferentially activated upon presentation of a scream facial expression, which
      is strongly negative, whereas the neurons in the vlPFC were activated upon
      presentation of coo, a facial expression with multiple meanings depending on the
      social context. Information analyses revealed that the amount of information
      conveyed by the amygdala neurons about the type of emotion transiently increased
      immediately after stimulus presentation. In contrast, the information conveyed by
      the vlPFC neurons showed sustained elevation during stimulus presentation.
      Therefore, our results suggest that the amygdala processes strong emotion roughly
      but rapidly, whereas the vlPFC spends a great deal of time processing ambiguous
      facial information in communication, and make an accurate decision from multiple
      possibilities based on memory. 

PMID- 26208843
TI  - Inter- and intra-subject variability of motor cortex plasticity following
      continuous theta-burst stimulation.
AB  - BACKGROUND: The potential of non-invasive brain stimulation (NIBS) for studying,
      and inducing, functionally relevant neuroplasticity is dependent on protocols
      that can induce lasting, robust and reliable effects. A current limiting factor
      is the large inter- and intra-subject variability in NIBS-induced neuroplastic
      responses. There has been some study of inter-subject response variability and
      factors that contribute to it; however, intra-subject response variability has,
      so far, received little investigation. OBJECTIVES: By testing participants on
      multiple occasions we aimed to (1) compare inter- and intra-subject variability
      of neuroplastic responses induced by continuous theta-burst stimulation (cTBS);
      (2) determine whether the transcranial magnetic stimulation (TMS) intensity used
      to measure cTBS-induced neuroplastic responses contributes to response
      variability; (3) determine whether assessment of factors known to influence
      response variability can be used to explain some of the variability in cTBS
      induced neuroplastic responses across experimental sessions. METHODS: In three
      separate experimental sessions, motor-evoked potential (MEP) input-output (IO)
      curves were obtained before and after cTBS, and questionnaire-based assessments
      of physical activity and perceived stress were obtained. RESULTS: cTBS-induced
      MEP suppression was greatest at the upper end of the IO curve (150-180% resting
      motor threshold; RMT) and most consistent across subjects and across experimental
      sessions when assessed with a TMS intensity of 150% RMT. The magnitude of cTBS
      induced MEP suppression evoked at 150% RMT correlated with self-reported
      perceived stress, but not with self-reported physical activity. CONCLUSIONS: The
      most reliable TMS intensity to probe cTBS-induced long-term depression (LTD)-like
      neuroplastic responses is 150% RMT. This is unlikely to simply be a ceiling
      effect and, we suggest, may be due to changes in the descending volley evoked at
      higher stimulus intensities. The perceived stress scale appears to be
      sufficiently sensitive to measure the influence of subject stress on LTD-like
      neuroplastic responses.

PMID- 26208844
TI  - Uric acid, indoxyl sulfate, and methylguanidine activate bulbospinal neurons in
      the RVLM via their specific transporters and by producing oxidative stress.
AB  - Patients with chronic renal failure often have hypertension, but the cause of
      hypertension, other than an excess of body fluid, is not well known. We
      hypothesized that the bulbospinal neurons in the rostral ventrolateral medulla
      (RVLM) are stimulated by uremic toxins in patients with chronic renal failure. To
      investigate whether RVLM neurons are sensitive to uremic toxins, such as uric
      acid, indoxyl sulfate, or methylguanidine, we examined changes in the membrane
      potentials (MPs) of bulbospinal RVLM neurons of Wister rats using the whole-cell
      patch-clamp technique during superfusion with these toxins. A brainstem-spinal
      cord preparation that preserved the sympathetic nervous system was used for the
      experiments. During uric acid, indoxyl sulfate, or methylguanidine superfusion,
      almost all the RVLM neurons were depolarized. To examine the transporters for
      these toxins on RVLM neurons, histological examinations were performed. The uric
      acid-, indoxyl sulfate-, and methylguanidine-depolarized RVLM neurons showed the
      presence of urate transporter 1 (URAT 1), organic anion transporter (OAT)1 or
      OAT3, and organic cation transporter (OCT)3, respectively. Furthermore, the toxin
      induced activities of the RVLM neurons were suppressed by the addition of an anti
      oxidation drug (VAS2870, an NAD(P)H oxidase inhibitor), and a histological
      examination revealed the presence of NAD(P)H oxidase (nox)2 and nox4 in these
      RVLM neurons. The present results show that uric acid, indoxyl sulfate, and
      methylguanidine directly stimulate bulbospinal RVLM neurons via specific
      transporters on these neurons and by producing oxidative stress. These uremic
      toxins may cause hypertension by activating RVLM neurons. 

PMID- 26208845
TI  - MicroRNAs as biomarkers of resilience or vulnerability to stress.
AB  - Identifying novel biomarkers of resilience or vulnerability to stress could
      provide valuable information for the prevention and treatment of stress-related
      psychiatric disorders. To investigate the utility of blood microRNAs as
      biomarkers of resilience or vulnerability to stress, microRNAs were assessed
      before and after 7days of chronic social defeat in rats. Additionally, microRNA
      profiles of two important stress-regulatory brain regions, the medial prefrontal
      cortex (mPFC) and basolateral amygdala (BLA), were assessed. Rats that displayed
      vulnerability to subsequent chronic stress exhibited reductions in circulating
      miR-24-2-5p, miR-27a-3p, miR-30e-5p, miR-3590-3p, miR-362-3p, and miR-532-5p
      levels. In contrast, rats that became resilient to stress displayed reduced
      levels of miR-139-5p, miR-28-3p, miR-326-3p, and miR-99b-5p compared to controls.
      In the mPFC, miR-126a-3p and miR-708-5p levels were higher in vulnerability
      compared to resilient rats. In the BLA, 77 microRNAs were significantly altered
      by stress but none were significantly different between resilient and vulnerable
      animals. These results provide proof-of-principle that assessment of circulating
      microRNAs is useful in identifying individuals who are vulnerable to the effects
      of future stress or individuals who have become resilient to the effects of
      stress. Furthermore, these data suggest that microRNAs in the mPFC but not in the
      BLA are regulators of resilience/vulnerability to stress. 

PMID- 26208846
TI  - Immunohistochemical and molecular profiling of histologically defined apocrine
      carcinomas of the breast.
AB  - Despite the marked improvement in the understanding of molecular mechanisms and
      classification of apocrine carcinoma, little is known about its specific
      molecular genetic alterations and potentially targetable biomarkers. In this
      study, we explored immunohistochemical and molecular genetic characteristics of
      37 invasive apocrine carcinomas using immunohistochemistry (IHC), fluorescent in
      situ hybridization (FISH), multiplex ligation-dependent probe amplification
      (MLPA), and next-generation sequencing (NGS) assays. IHC revealed frequent E
      cadherin expression (89%), moderate (16%) proliferation activity [Ki-67,
      phosphohistone H3], infrequent (~10%) expression of basal cell markers [CK5/6,
      CK14, p63, caveolin-1], loss of PTEN (83%), and overexpression of HER2 (32%),
      EGFR (41%), cyclin D1 (50%), and MUC-1 (88%). MLPA assay revealed gene copy gains
      of MYC, CCND1, ZNF703, CDH1, and TRAF4 in 50% or greater of the apocrine
      carcinomas, whereas gene copy losses frequently affected BRCA2 (75%), ADAM9
      (54%), and BRCA1 (46%). HER2 gain, detected by MLPA in 38% of the cases, was in
      excellent concordance with HER2 results obtained by IHC/FISH (kappa = 0.915, P <
      .001). TOP2A gain was observed in one case, while five cases (21%) exhibited
      TOP2A loss. Unsupervised hierarchical cluster analysis revealed two distinct
      clusters: HER2-positive and HER2-negative (P = .03 and .04, respectively). NGS
      assay revealed mutations of the TP53 (2 of 7, 29%), BRAF/KRAS (2 of 7, 29%), and
      PI3KCA/PTEN genes (7 of 7, 100%). We conclude that morphologically defined
      apocrine carcinomas exhibit complex molecular genetic alterations that are
      consistent with the "luminal-complex" phenotype. Some of the identified molecular
      targets are promising biomarkers; however, functional studies are needed to prove
      these observations. 

PMID- 26208847
TI  - Expression of adhesion molecules and epithelial-mesenchymal transition factors in
      medullary carcinoma of the colorectum.
AB  - Medullary carcinoma (MC) of the colorectum is known as a rare variant with
      favorable prognosis despite its poorly differentiated morphology. The mechanism
      of its favorable behavior has been unclear. Here, we compared the expressions of
      adhesion molecules and epithelial-mesenchymal transition (EMT)-related proteins
      in the central portion and invasive front between 43 MCs and 30 poorly
      differentiated adenocarcinomas (PDAs). The expressions of membranous E-cadherin
      (P < .0001), beta-catenin (P < .0001) and claudin 1 (P = .0036) were
      significantly preserved in the invasive front of the MCs compared to those in the
      invasive front of the PDAs. E-cadherin membranous expression was also
      significantly preserved in the central portion of the MCs (P = .0178). Nuclear
      beta-catenin expression in both the central portion (P = .0463) and invasive
      front (P = .0346) of the MCs was significantly less frequent compared to that in
      the PDAs. Snail (P = .0035) and Twist1 (P = .0463) expressions in the invasive
      front of the MCs were significantly less frequent compared to the PDAs,
      suggesting that the EMT phenomenon may occur rarely in colorectal MC. Reduced
      membranous E-cadherin expression in the MC central portion was significantly
      correlated with poor clinical outcome (P = .0086). Our immunohistochemical
      results indicate that preserved adhesion molecule protein and less frequent
      expression of EMT-related transcription factors in the invasive front contribute
      to the favorable prognosis of colorectal MCs. We suggest that a reduced
      expression of E-cadherin in the central portion might be a good biomarker for an
      unfavorable prognosis in cases of MC. 

PMID- 26208848
TI  - US oncologists call for government regulation to curb drug price rises.

PMID- 26208849
TI  - Expert views on the factors enabling good end of life care for people with
      dementia: a qualitative study.
AB  - BACKGROUND: Dementia, of all long term illnesses, accounts for the greatest
      chronic disease burden, and the number of people with age-related diseases like
      dementia is predicted to double by 2040. People with advanced dementia experience
      similar symptoms to those dying with cancer yet professional carers find
      prognostication difficult and struggle to meet palliative care needs, with
      physical symptoms undetected and untreated. While elements of good practice in
      this area have been identified in theory, the factors which enable such good
      practice to be implemented in real world practice need to be better understood.
      The aim of this study was to determine expert views on the key factors
      influencing good practice in end of life care for people with dementia. METHODS:
      Semi-structured telephone and face-to-face interviews with topic guide, verbatim
      transcription and thematic analysis. Interviews were conducted with experts in
      dementia care and/or palliative care in England (n = 30). RESULTS: Four key
      factors influencing good practice in end of life care for people with dementia
      were identified from the expert interviews: leadership and management of care,
      integrating clinical expertise, continuity of care, and use of guidelines.
      CONCLUSIONS: The relationships between the four key factors are important.
      Leadership and management of care have implications for the successful
      implementation of guidelines, while the appropriate and timely use of clinical
      expertise could prevent hospitalisation and ensure continuity of care. A lack of
      integration across health and social care can undermine continuity of care.
      Further work is needed to understand how existing guidelines and tools contribute
      to good practice. DISCLAIMER: This article presents independent research funded
      by the National Institute for Health Research (NIHR) under its Programme Grants
      for Applied Research programme (Grant Reference Number RP-PG-0611-20005). The
      views expressed are those of the author(s) and not necessarily those of the NHS,
      the NIHR or the Department of Health.

PMID- 26208850
TI  - Evaluation of an association between plasma total homocysteine and schizophrenia
      by a Mendelian randomization analysis.
AB  - BACKGROUND: The results of meta-analyses conducted by previous association
      studies between total homocysteine and schizophrenia suggest that an elevated
      total homocysteine level is a risk factor for schizophrenia. However,
      observational studies have potential limitations, such as confounding and reverse
      causation. In the present study, we evaluated a causal relationship between
      plasma total homocysteine and schizophrenia by conducting a Mendelian
      randomization analysis. METHODS: We used the MTHFR C677T polymorphism as an
      instrumental variable, which affects the plasma total homocysteine levels. To
      calculate the risk estimate for the association of this single nucleotide
      polymorphism (SNP) with schizophrenia, we conducted a meta-analysis of case
      control studies that comprise a total of 11,042 patients with schizophrenia and
      14,557 control subjects. We obtained an estimate for the association of this SNP
      with the plasma total homocysteine levels from a meta-analysis of genome-wide
      association studies comprising 44,147 individuals. RESULTS: By combining these
      two estimates, we demonstrated a significant effect of the plasma total
      homocysteine on schizophrenia risk, representing an OR of 2.15 (95 % CI = 1.39
      3.32; p = 5.3 x 10(-4)) for schizophrenia per 1-SD increase in the natural log
      transformed plasma total homocysteine levels. CONCLUSIONS: We provided evidence
      of a causal relationship between the plasma total homocysteine and schizophrenia,
      and this result will add insight into the pathology and treatment of
      schizophrenia.

PMID- 26208851
TI  - What variables are important in predicting bovine viral diarrhea virus? A random
      forest approach.
AB  - Bovine viral diarrhea virus (BVDV) causes one of the most economically important
      diseases in cattle, and the virus is found worldwide. A better understanding of
      the disease associated factors is a crucial step towards the definition of
      strategies for control and eradication. In this study we trained a random forest
      (RF) prediction model and performed variable importance analysis to identify
      factors associated with BVDV occurrence. In addition, we assessed the influence
      of features selection on RF performance and evaluated its predictive power
      relative to other popular classifiers and to logistic regression. We found that
      RF classification model resulted in an average error rate of 32.03% for the
      negative class (negative for BVDV) and 36.78% for the positive class (positive
      for BVDV).The RF model presented area under the ROC curve equal to 0.702.
      Variable importance analysis revealed that important predictors of BVDV
      occurrence were: a) who inseminates the animals, b) number of neighboring farms
      that have cattle and c) rectal palpation performed routinely. Our results suggest
      that the use of machine learning algorithms, especially RF, is a promising
      methodology for the analysis of cross-sectional studies, presenting a
      satisfactory predictive power and the ability to identify predictors that
      represent potential risk factors for BVDV investigation. We examined classical
      predictors and found some new and hard to control practices that may lead to the
      spread of this disease within and among farms, mainly regarding poor or neglected
      reproduction management, which should be considered for disease control and
      eradication.

PMID- 26208852
TI  - JAK kinase inhibitors for the treatment of acute lymphoblastic leukemia.
AB  - Recent studies of acute lymphoblastic leukemia have identified activating
      mutations in components of the interleukin-7 receptor complex (IL7R, JAK1, and
      JAK3). It will be of interest to investigate both JAK1 and JAK3 kinase inhibitors
      as targeted agents for these leukemias. 

PMID- 26208853
TI  - Common and specific downstream signaling targets controlled by Tlr2 and Tlr5
      innate immune signaling in zebrafish.
AB  - BACKGROUND: Although the responses to many pathogen associated molecular patterns
      (PAMPs) in cell cultures and extracted organs are well characterized, there is
      little known of transcriptome responses to PAMPs in whole organisms. To
      characterize this in detail, we have performed RNAseq analysis of responses of
      zebrafish embryos to injection of PAMPs in the caudal vein at one hour after
      exposure. We have compared two ligands that in mammals have been shown to
      specifically activate the TLR2 and TLR5 receptors: Pam3CSK4 and flagellin,
      respectively. RESULTS: We identified a group of 80 common genes that respond with
      high stringency selection to stimulations with both PAMPs, which included several
      well-known immune marker genes such as il1b and tnfa. Surprisingly, we also
      identified sets of 48 and 42 genes that specifically respond to either Pam3CSK4
      or flagellin, respectively, after a comparative filtering approach. Remarkably,
      in the Pam3CSK4 specific set, there was a set of transcription factors with more
      than 2 fold-change, as confirmed by qPCR analyses, including cebpb, fosb, nr4a1
      and egr3. We also showed that the regulation of the Pam3CSK4 and flagellin
      specifically responding sets is inhibited by knockdown of tlr2 or tlr5,
      respectively. CONCLUSIONS: Our studies show that Pam3CSK4 and flagellin can
      stimulate the Tlr2 and Tlr5 signaling pathways leading to common and specific
      responses in the zebrafish embryo system.

PMID- 26208855
TI  - Sequence structure of Lowary/Widom clones forming strong nucleosomes.
AB  - Lowary and Widom selected from random sequences those which form exceptionally
      stable nucleosomes, including clone 601, the current champion of strong
      nucleosome (SN) sequences. This unique sequence database (LW sequences) carries
      sequence elements which confer stability on the nucleosomes formed on the
      sequences, and, thus, may serve as source of information on the structure of
      "ideal" or close to ideal nucleosome DNA sequence. An important clue is also
      provided by crystallographic study of Vasudevan and coauthors on clone 601
      nucleosomes. It demonstrated that YR.YR dinucleotide stacks (primarily TA.TA)
      follow one another at distances 10 or 11 bases or multiples thereof, such that
      they all are located on the interface between DNA and histone octamer. Combining
      this important information with alignment of the YR-containing 10-mers and 11
      mers from LW sequences, the bendability matrices of the stable nucleosome DNA are
      derived. The matrices suggest that the periodically repeated TA (YR), RR, and YY
      dinucleotides are the main sequence features of the SNs. This consensus coincides
      with the one for recently discovered SNs with visibly periodic DNA sequences.
      Thus, the experimentally observed stable LW nucleosomes and SNs derived
      computationally appear to represent the same entity - exceptionally stable SNs. 

PMID- 26208854
TI  - An evaluation of evidence-based paediatric injury prevention policies across
      Canada.
AB  - BACKGROUND: Policies to reduce injury among Canadians can be controversial and
      there is variability in the enactment of injury prevention laws across the
      country. In general, laws are most effective when they are based on good research
      evidence, supported by widespread public awareness and education, and maintained
      by consistent enforcement strategies. The purpose of this study was to document
      and compare key informants' perceptions of the quality, awareness, and
      enforcement of three evidence-based paediatric injury prevention policies
      (bicycle helmet legislation, child booster seat legislation, graduated driver
      licensing) among Canadian provinces and territories. METHODS: We identified best
      practices related to each policy, then developed an online survey to ascertain
      the extent to which each jurisdiction's policy aligned with best practices,
      whether experts believed that the public was aware of the policy and whether it
      was enforced. The survey was distributed using a snowball sampling strategy to
      key informants across Canada. RESULTS: Thirty-eight key informants responded to
      the bicycle helmet survey, with 73 and 35 key informants for the booster seat and
      graduated driver licensing surveys, respectively. Respondent's perceptions of the
      policies varied substantially. Key informants indicated that residents are not
      always aware of legislation, and legislation is not consistently enforced. These
      results suggest that child health policy is not always guided by evidence.
      CONCLUSIONS: There was variation between evidence and the policies related to
      paediatric injury prevention among Canadian provinces and territories. Experts
      generally rate their policies more highly when they align with evidence and best
      practice. There is room for improvement and harmonization of injury prevention
      policies.

PMID- 26208856
TI  - Cdc7 overexpression is an independent prognostic marker and a potential
      therapeutic target in colorectal cancer.
AB  - BACKGROUND: Cdc7 is a widely expressed protein kinase implicated in cell
      division, cell cycle checkpoint mechanisms and cancer progression. Recently, it
      has been suggested as a target for anti-cancer therapy. METHODS: To determine the
      relationship of Cdc7 protein expression with tumor phenotype, molecular features
      and prognosis, 1800 colorectal carcinomas were analyzed by immunohistochemistry
      on a tissue microarray. RESULTS: Cdc7 expression was considered negative in
      33.6%, weak in 57.2% and strong in 9.2% of 1711 interpretable CRCs. Loss of Cdc7
      expression was significantly associated with high tumor stage (p < 0.0001) and
      high tumor grade (p = 0.0077), but was unrelated to the nodal status (p =
      0.5957). Moreover, a link between Cdc7 expression and the tubular histological
      tumor type was seen (p < 0.0001). p53 and Cdc7 expression were significantly
      linked to each other (p = 0.0013). In a multivariate survival analysis, strong
      Cdc7 expression of CRC was an independent marker of improved patient survival (p
      = 0.0031). CONCLUSION: Our data show that Cdc7 is highly expressed in CRC and a
      potential therapeutic target in a subset of cancers with high p53 expression.
      Moreover, our findings strongly argue for a clinical utility of Cdc7
      immunostaining as an independent prognostic biomarker in colorectal cancer
      enabling to select patients for adjuvant treatment.

PMID- 26208857
TI  - Red cabbage anthocyanins as inhibitors of lipopolysaccharide-induced oxidative
      stress in blood platelets.
AB  - LPS is a Gram-negative bacteria endotoxin, which is an important pro-inflammatory
      agent. Blood platelets take part both in inflammatory processes and in
      pathogenesis of septic shock following accumulation of LPS. As a platelet agonist
      LPS causes the intraplatelet overproduction of ROS/RNS that are responsible for
      adverse modifications in the structure of platelet compounds being associated
      with a development of platelet-dependent diseases. Existing evidence suggests
      that anthocyanins (ATH) are able to protect the circulatory system. The
      antioxidative properties of ATH are believed to be mainly responsible for their
      positive health effects. The main goal of the present in vitro study was to
      investigate the potential protective properties of red cabbage ATH against
      oxidative damage induced by LPS in blood platelets. Exposure of platelets to LPS
      resulted in carbonyl group increase, 3-nitrotyrosine formation, lipid
      peroxidation and O2(*-) generation. We have shown that ATH extract effectively
      decreased oxidative stress induced by LPSs. The in silico analysis demonstrated
      that both cyanin and LPS were located at the same region of human TLR4-MD-2
      complex. Our findings suggest that there could be two-way ATH platelet protection
      mechanism, by their antioxidant properties and directly by binding with TLRs.

PMID- 26208858
TI  - Digestive alkaline proteases from thornback ray (Raja clavata): Characteristics
      and applications.
AB  - This study describes the characterization of a crude protease extract from
      thornback ray (Raja clavata) and its evaluation in liquid detergent and in
      deproteinizattion of shrimp waste. At least five clear caseinolytic proteases
      bands were observed in a zymogram. The crude protease showed optimum activity at
      pH 8.0 and 50  degrees C, and it was highly stable over pH range from 8.0 to
      11.0. Proteolytic enzymes were very stable in non-ionic surfactants and in the
      presence of oxidizing agents, maintaining 70% of their activity after incubation
      for 1 h at 30  degrees C in the presence of 1% sodium perborate. In addition,
      they showed high stability and compatibility with various liquid laundry
      detergents available in the Tunisian market. The crude extract retained 100% of
      its activity after preincubation for 60 min at 30  degrees C in the presence of
      Nadhif Perfect, Textil and Carrefour laundry detergents. Further, proteases from
      R. clavata viscera were used for shrimp waste deproteinization in the process of
      chitin preparation. The percent of protein removal after 3 h hydrolysis at 45 
      degrees C with an enzyme/substrate ratio of 30 U/mg of proteins was 74%. These
      results suggest that enzymatic deproteinization of shrimp wastes by fish
      endogenous alkaline proteases could be applicable to the chitin production
      process.

PMID- 26208859
TI  - Thoracic and abdominal aortic diameters in a general population: MRI-based
      reference values and association with age and cardiovascular risk factors.
AB  - OBJECTIVES: To generate reference values for thoracic and abdominal aortic
      diameters determined by magnetic resonance imaging (MRI) and analyse their
      association with cardiovascular risk factors in the general population. METHODS:
      Data from participants (n = 1759) of the Study of Health in Pomerania were used
      for analysis in this study. MRI measurement of thoracic and abdominal aortic
      diameters was performed. Parameters for calculation of reference values according
      to age and sex analysis were provided. Multivariable linear regression models
      were used for determination of aortic diameter-related risk factors, including
      smoking, blood pressure (BP), high-density lipoprotein cholesterol (HDL-C).
      RESULTS: For the ascending aorta (beta = -0.049, p < 0.001), the aortic arch
      (beta = -0.061, p < 0.001) and the subphrenic aorta (beta = -0.018, p = 0.004),
      the body surface area (BSA)-adjusted diameters were lower in men. Multivariable
      adjusted models revealed significant increases in BSA-adjusted diameters with age
      for all six aortic segments (p < 0.001). Consistent results for all segments were
      observed for the positive associations of diastolic BP (beta = 0.001; 0.004) and
      HDL (beta = 0.035; 0.087) with BSA-adjusted aortic diameters and for an inverse
      association of systolic BP (beta = -0.001). CONCLUSIONS: Some BSA-adjusted median
      aortic diameters are smaller in men than in women. All diameters increase with
      age, diastolic blood pressure and HDL-C and decrease as systolic BP increases.
      KEY POINTS: * Median aortic diameter increases with age and diastolic blood
      pressure. * Median aortic diameter is larger in men than in women. * Some BSA
      adjusted median aortic diameters are smaller in men than in women.

PMID- 26208860
TI  - Building a Terminal: Mechanisms of Presynaptic Development in the CNS.
AB  - To create a presynaptic terminal, molecular signaling events must be orchestrated
      across a number of subcellular compartments. In the soma, presynaptic proteins
      need to be synthesized, packaged together, and attached to microtubule motors for
      shipment through the axon. Within the axon, transport of presynaptic packages is
      regulated to ensure that developing synapses receive an adequate supply of
      components. At individual axonal sites, extracellular interactions must be
      translated into intracellular signals that can incorporate mobile transport
      vesicles into the nascent presynaptic terminal. Even once the initial recruitment
      process is complete, the components and subsequent functionality of presynaptic
      terminals need to constantly be remodeled. Perhaps most remarkably, all of these
      processes need to be coordinated in space and time. In this review, we discuss
      how these dynamic cellular processes occur in neurons of the central nervous
      system in order to generate presynaptic terminals in the brain.

PMID- 26208861
TI  - Plasmodium transmission blocking activities of Vernonia amygdalina extracts and
      isolated compounds.
AB  - BACKGROUND: Medicinal plants are a validated source for discovery of new leads
      and standardized herbal medicines. The aim of this study was to assess the
      activity of Vernonia amygdalina leaf extracts and isolated compounds against
      gametocytes and sporogonic stages of Plasmodium berghei and to validate the
      findings on field isolates of Plasmodium falciparum. METHODS: Aqueous (Ver-H2O)
      and ethanolic (Ver-EtOH) leaf extracts were tested in vivo for activity against
      sexual and asexual blood stage P. berghei parasites. In vivo transmission
      blocking effects of Ver-EtOH and Ver-H2O were estimated by assessing P. berghei
      oocyst prevalence and density in Anopheles stephensi mosquitoes. Activity
      targeting early sporogonic stages (ESS), namely gametes, zygotes and ookinetes
      was assessed in vitro using P. berghei CTRPp.GFP strain. Bioassay guided
      fractionation was performed to characterize V. amygdalina fractions and molecules
      for anti-ESS activity. Fractions active against ESS of the murine parasite were
      tested for ex vivo transmission blocking activity on P. falciparum field
      isolates. Cytotoxic effects of extracts and isolated compounds vernolide and
      vernodalol were evaluated on the human cell lines HCT116 and EA.hy926. RESULTS:
      Ver-H2O reduced the P. berghei macrogametocyte density in mice by about 50% and
      Ver-EtOH reduced P. berghei oocyst prevalence and density by 27 and 90%,
      respectively, in An. stephensi mosquitoes. Ver-EtOH inhibited almost completely
      (>90%) ESS development in vitro at 50 MUg/mL. At this concentration, four
      fractions obtained from the ethylacetate phase of the methanol extract displayed
      inhibitory activity >90% against ESS. Three tested fractions were also found
      active against field isolates of the human parasite P. falciparum, reducing
      oocyst prevalence in Anopheles coluzzii mosquitoes to one-half and oocyst density
      to one-fourth of controls. The molecules and fractions displayed considerable
      cytotoxicity on the two tested cell-lines. CONCLUSIONS: Vernonia amygdalina
      leaves contain molecules affecting multiple stages of Plasmodium, evidencing its
      potential for drug discovery. Chemical modification of the identified hit
      molecules, in particular vernodalol, could generate a library of druggable
      sesquiterpene lactones. The development of a multistage phytomedicine designed as
      preventive treatment to complement existing malaria control tools appears a
      challenging but feasible goal.

PMID- 26208862
TI  - Mental Illness Drives Hospitalizations for Detained California Youth.
AB  - PURPOSE: The purpose of the study was to describe inpatient hospitalization
      patterns among detained and nondetained youth in a large, total population of
      hospitalized adolescents in California. METHODS: We examined the unmasked
      California Office of Statewide Health Planning and Development Patient Discharge
      Dataset from 1997 to 2011. We considered hospitalized youth aged 11-18 years
      "detained" if admitted to California hospitals from detention, transferred from
      hospital to detention, or both. We compared discharge diagnoses and length of
      stay between detained youth and their nondetained counterparts in the general
      population. RESULTS: There were 11,367 hospitalizations for detained youth.
      Hospitalizations differed for detained versus nondetained youth: 63% of all
      detained youth had a primary diagnosis of mental health disorder (compared with
      19.8% of nondetained youth). Detained girls were disproportionately affected,
      with 74% hospitalized for a primary mental health diagnosis. Detained youth
      hospitalized for mental health disorder had an increased median length of stay
      compared with nondetained inpatient youth with mental illness (>= 6 days vs. 5
      days, respectively). This group difference was heightened in the presence of
      minority status, public insurance, and concurrent substance abuse. Hospitalized
      detained youth discharged to chemical dependency treatment facilities had the
      longest hospital stays (>= 43 days). CONCLUSIONS: Detained juvenile offenders are
      hospitalized for very different reasons than the general adolescent population.
      Mental illness, often with comorbid substance abuse, requiring long inpatient
      stays, represents the major cause for hospitalization. These findings underscore
      the urgent need for effective, well-coordinated mental health services for youth
      before, during, and after detention.

PMID- 26208863
TI  - Baseline Physiologic and Psychosocial Characteristics of Transgender Youth
      Seeking Care for Gender Dysphoria.
AB  - PURPOSE: The purpose of this study was to describe baseline characteristics of
      participants in a prospective observational study of transgender youth (aged 12
      24 years) seeking care for gender dysphoria at a large, urban transgender youth
      clinic. METHODS: Eligible participants presented consecutively for care at
      between February 2011 and June 2013 and completed a computer-assisted survey at
      their initial study visit. Physiologic data were abstracted from medical charts.
      Data were analyzed by descriptive statistics, with limited comparisons between
      transmasculine and transfeminine participants. RESULTS: A total of 101 youth were
      evaluated for physiologic parameters, 96 completed surveys assessing psychosocial
      parameters. About half (50.5%) of the youth were assigned a male sex at birth.
      Baseline physiologic values were within normal ranges for assigned sex at birth.
      Youth recognized gender incongruence at a mean age of 8.3 years (standard
      deviation = 4.5), yet disclosed to their family much later (mean = 17.1; standard
      deviation = 4.2). Gender dysphoria was high among all participants. Thirty-five
      percent of the participants reported depression symptoms in the clinical range.
      More than half of the youth reported having thought about suicide at least once
      in their lifetime, and nearly a third had made at least one attempt. CONCLUSIONS:
      Baseline physiologic parameters were within normal ranges for assigned sex at
      birth. Transgender youth are aware of the incongruence between their internal
      gender identity and their assigned sex at early ages. Prevalence of depression
      and suicidality demonstrates that youth may benefit from timely and appropriate
      intervention. Evaluation of these youth over time will help determine the impact
      of medical intervention and mental health therapy.

PMID- 26208864
TI  - Recurrent and non-recurrent feline injection-site sarcoma: computed tomographic
      and ultrasonographic findings.
AB  - OBJECTIVES: This study describes the sonographic and computed tomographic (CT)
      characteristics of primary and recurrent feline injection-site sarcomas (FISSs).
      METHODS: Between 2005 and 2013, 32 cats were selected for prospective and
      retrospective studies. Tumor shape and margins, presence of thickening of the
      adipose tissue, muscular and bone involvement, pre- and postcontrast attenuation,
      blurring of fat planes, calcification and liquefactive necrosis, intratumoral
      areas and skip metastasis were analyzed in CT scans. Echogenicity, echotexture,
      tumor margins and peritumoral tissue characteristics were analyzed by ultrasound
      (US). RESULTS: Irregular shape (62.5%) with digitiform projections (100.0%),
      mixed (peripheral and intratumoral) contrast enhancement (67.7%), blurring of fat
      planes (68.8%) and signs of liquefactive intratumoral necrosis (68.8%) were the
      prevailing CT findings. Ultrasonography revealed irregular tumor margins,
      peripheral hyperechoic capsule-like rim, heterogeneous echotexture, and
      hyperechoic tissue contiguous with the formations and thickening of adjacent
      subcutaneous tissues in all cases. Mixed echogenicity with areas suggestive of
      tumor liquefactive necrosis was documented in 83.3% of cases. Skip metastases
      were highly correlated with tumor recurrence (P = 0.001). The incidence of
      muscular involvement tended to be higher (P = 0.003) in tumors presenting with
      thickening of adjacent adipose tissue. CONCLUSIONS AND RELEVANCE: CT and US
      features common to FISS lesions were highlighted in this study. The imaging
      modalities employed allowed assessment of peritumoral inflammation, particularly
      adipose tissue inflammation. Imaging data may contribute to FISS diagnosis,
      therapeutic planning and patient follow-up.

PMID- 26208865
TI  - Prevalence of intestinal parasites in breeding cattery cats in Japan.
AB  - OBJECTIVES: To address the lack of up-to-date published data, the present study
      assessed the prevalence of intestinal parasites in breeding catteries in Japan.
      METHODS: Fresh faecal samples were randomly collected from 342 cats (aged 1 month
      to 12 years) in seven breeding catteries in Japan, located in prefectures of
      Nagano (n = 2), Saitama (n = 1), Aichi (n = 2), Gifu (n = 1) and Miyagi (n = 1),
      on a single occasion. The samples were tested for the presence of Giardia species
      copro-antigen using a commercially available enzyme-linked immunosorbent assay
      kit. Other intestinal parasites were identified microscopically using the
      formalin-ethyl acetate sedimentation technique. RESULTS: The total prevalence of
      intestinal parasites was 20.8%; only two genera of protozoa (Giardia species:
      18.7% and Cystoisospora species: 5.0%) were detected. Coinfections of both
      protozoans were recorded in 2.9% of cats. In contrast, no helminths were
      detected. The presence of total infection, Giardia species, Cystoisospora species
      and multiple infections in cats <1 year old were significantly more prevalent
      than in cats ?1 year old. There were no significant differences among faecal
      conditions with or without intestinal parasites. Giardia species infection was
      present in samples from all breeding catteries, except for one facility.
      Cystoisospora species and coinfections were shown in four and two breeding
      catteries, respectively. The prevalence of intestinal parasites was markedly
      variable among the breeding catteries. CONCLUSIONS AND RELEVANCE: The present
      study demonstrates the significance of Giardia species and Cystoisospora species
      infections in breeding cattery cats. Additionally, it is suggested that
      environmental contamination is the most important factor influencing the
      prevalence of protozoal infections in breeding catteries.

PMID- 26208866
TI  - Comparison of non-contact infrared thermometry and rectal thermometry in cats.
AB  - OBJECTIVES: Body temperature is commonly used for assessing health and
      identifying infectious diseases in cats. Rectal thermometry, the most commonly
      used method, is stressful, invasive and time consuming. Non-contact infrared
      thermometry (NIRT) has been used with mixed success to measure temperature in
      humans and other species. The purpose of this study was to determine if NIRT
      measurements were comparable to rectal temperature measurements or, if not highly
      correlated, could at least identify cats in the hypothermic or hyperthermic range
      in need of further evaluation. METHODS: From a total of six NIRT devices and 15
      anatomic sites, three devices and three sites (pinna, gingiva and perineum) with
      the highest correlation to rectal temperature were selected for further study.
      Measurements were made in 188 adult cats housed indoors at animal shelters,
      veterinary clinics and private homes across a wide range of body temperatures and
      compared with rectal temperatures. RESULTS: Bland-Altman analysis revealed poor
      agreement between NIRT and rectal thermometry. The mean NIRT measurements ranged
      from 0.7-1.3 degrees C below the mean rectal measurements, but the effect was not
      consistent; NIRT measurements tended to exceed rectal measurements in hypothermic
      cats and fall below rectal measurements in normothermic and hyperthermic cats.
      CONCLUSIONS AND RELEVANCE: The accuracy of temperature measurements using NIRT
      devices is not reliable for clinical use in cats.

PMID- 26208867
TI  - A meta-analysis of the performance of the PimaTM CD4 for point of care testing.
AB  - BACKGROUND: The Alere point-of-care (POC) PimaTM CD4 analyzer allows for
      decentralized testing and expansion to testing antiretroviral therapy (ART)
      eligibility. A consortium conducted a pooled multi-data technical performance
      analysis of the Pima CD4. METHODS: Primary data (11,803 paired observations)
      comprised 22 independent studies between 2009-2012 from the Caribbean, Asia, Sub
      Saharan Africa, USA and Europe, using 6 laboratory-based reference technologies.
      Data were analyzed as categorical (including binary) and numerical (absolute)
      observations using a bivariate and/or univariate random effects model when
      appropriate. RESULTS: At a median reference CD4 of 383 cells/MUl the mean Pima
      CD4 bias is -23 cells/MUl (average bias across all CD4 ranges is 10 % for venous
      and 15% for capillary testing). Sensitivity of the Pima CD4 is 93% (95%
      confidence interval [CI] 91.4% - 94.9%) at 350 cells/MUl and 96% (CI 95.2% -
      96.9%) at 500 cells/MUl, with no significant difference between venous and
      capillary testing. Sensitivity reduced to 86% (CI 82% - 89%) at 100 cells/MUl
      (for Cryptococcal antigen (CrAg) screening), with a significant difference
      between venous (88%, CI: 85% - 91%) and capillary (79%, CI: 73% - 84%) testing.
      Total CD4 misclassification is 2.3% cases at 100 cells/MUl, 11.0% at 350
      cells/MUl and 9.5 % at 500 cells/MUl, due to higher false positive rates which
      resulted in more patients identified for treatment. This increased by 1.2%, 2.8%
      and 1.8%, respectively, for capillary testing. There was no difference in Pima
      CD4 misclassification between the meta-analysis data and a population subset of
      HIV+ ART naive individuals, nor in misclassification among operator cadres. The
      Pima CD4 was most similar to Beckman Coulter PanLeucogated CD4, Becton Dickinson
      FACSCalibur and FACSCount, and less similar to Partec CyFlow reference
      technologies. CONCLUSIONS: The Pima CD4 may be recommended using venous-derived
      specimens for screening (100 cells/MUl) for reflex CrAg screening and for HIV ART
      eligibility at 350 cells/MUl and 500 cells/MUl thresholds using both capillary
      and venous derived specimens. These meta-analysis findings add to the knowledge
      of acceptance criteria of the Pima CD4 and future POC tests, but implementation
      and impact will require full costing analysis.

PMID- 26208868
TI  - Barriers and facilitators of suicide risk assessment in emergency departments: a
      qualitative study of provider perspectives.
AB  - OBJECTIVE: To understand emergency department (ED) providers' perspectives
      regarding the barriers and facilitators of suicide risk assessment and to use
      these perspectives to inform recommendations for best practices in ED suicide
      risk assessment. METHODS: Ninety-two ED providers from two hospital systems in a
      Midwestern state responded to open-ended questions via an online survey that
      assessed their perspectives on the barriers and facilitators to assess suicide
      risk as well as their preferred assessment methods. Responses were analyzed using
      an inductive thematic analysis approach. RESULTS: Qualitative analysis yielded
      six themes that impact suicide risk assessment. Time, privacy, collaboration and
      consultation with other professionals and integration of a standard screening
      protocol in routine care exemplified environmental and systemic themes. Patient
      engagement/participation in assessment and providers' approach to communicating
      with patients and other providers also impacted the effectiveness of suicide risk
      assessment efforts. CONCLUSION: The findings inform feasible suicide risk
      assessment practices in EDs. Appropriately utilizing a collaborative,
      multidisciplinary approach to assess suicide-related concerns appears to be a
      promising approach to ameliorate the burden placed on ED providers and facilitate
      optimal patient care. Recommendations for clinical care, education, quality
      improvement and research are offered.

PMID- 26208869
TI  - Haematologic alterations caused by Ipomoea carnea in experimental poisoning of
      guinea pig.
AB  - Ipomoea carnea subsp. fistulosa (Convolvulaceae) causes poisoning of goats, sheep
      and cattle in many tropical and subtropical countries. The pathophysiology of
      this poisoning mainly involves an abnormal glycoprotein metabolism. The aim of
      this study was to describe the potential toxicity of I. carnea in a guinea pig
      model through its effect on hematopoiesis in a time course study of 40 days.
      Experimental poisoning was achieved by feeding animals with "small balls"
      prepared with milled leaves of I. carnea mixed with commercial crushed pellets
      for rodents. Hematologic and biochemical parameters, bone marrow and
      spleencellularities, histopathologic evaluations and lectin-histochemistrywere
      performed during the scheduled time of the study.The treatment with "small balls"
      caused significant changes in the weight of spleen, a notable decrease in
      peripheral red blood cells, and concomitantwith morphological and
      histopathologicalalterationsin hematopoietic tissues. Overall, the present study
      suggested that 20 days ofthis treatmentcouldbe enough to develop bone marrow
      hypoplasia and vacuolation of white cells of spleen, blood and lymph nodes with a
      transient erythropoietic contribution of the splenic niche.Moreover, this work
      provides a cheap and simple method for detecting preclinical cases of
      intoxication by I. carnea in livestock. 

PMID- 26208870
TI  - Rat malignant fibrous histiocytoma (MFH)-derived cloned cell lines (MT-8 and MT
      9) show different differentiation in mesenchymal stem cell lineage.
AB  - Malignant fibrous histiocytomas (MFHs) show a storiform growth pattern consisting
      of fibroblastic, histiocytic and undifferentiated mesenchymal cells with possible
      multipotency. Because MFH-like tumors are induced experimentally by some
      chemicals and materials, it is important to know the histogenesis of MFHs. We
      analyzed in vitro and in vivo characteristics of two cloned cell lines (MT-8 and
      MT-9) established from a spontaneous MFH found in an aged F344 rat. MT-8 and MT-9
      cultured cells and their tumors induced in syngeneic rats by injection were
      investigated morphologically, and their tumors were evaluated by
      immunohistochemistry. Gene expression profiles of their cultures and induced
      tumors were analyzed by the comprehensive gene analysis. MT-8 cells had less
      developed organelles and the induced tumors represented histological
      characteristics of undifferentiated sarcoma (sarcoma not otherwise specified
      (NOS)), whereas MT-9 cells had relatively well-developed intracytoplasmic
      organelles such as endoplasmic reticulum, mitochondria and lysosomes and the
      tumors showed a storiform growth pattern typical of MFHs. MT-8 and MT-9 tumors
      were immuno-positive for vimentin, and the reactivity for stem cell markers
      (nestin, CD90, CD34, and A3) appeared to be greater in MT-9 tumor cells, and
      their tumor cells did not react to markers for well-differentiated cells of
      epithelial, myogenic and neurogenic tissues except for faint reaction for S-100
      protein in MT-9 tumors. The gene analyses revealed that genes relating to "cell
      differentiation" were more activated in MT-9 than MT-8 tumors, whereas those
      involved in "cell cycle" were greater in MT-8 than MT-9 tumors. In MT-8 and MT-9,
      additionally, genes involved in "cell differentiation" were much greater in their
      tumors than in their cultures. These findings indicate that MT-8 cells are poorly
      differentiated mesenchymal stem cells which induce sarcomas NOS, whereas MT-9
      cells, which can develop typical MFHs, have more differentiated stem cell nature
      with greater multipotential differentiation. In MFHs, collectively, MT-8 and MT-9
      cells are regarded as "tumor stem cells" and "tumor precursors" in the stem cell
      lineage, respectively, according to the concept of "cancer stem cell theory". 

PMID- 26208871
TI  - Significant feed-forward connectivity revealed by high frequency components of
      BOLD fMRI signals.
AB  - Granger causality analysis has been suggested as a method of estimating causal
      modulation without specifying the direction of information flow a priori. Using
      BOLD-contrast functional MRI (fMRI) data, such analysis has been typically
      implemented in the time domain. In this study, we used magnetic resonance inverse
      imaging, a method of fast fMRI enabled by massively parallel detection allowing
      up to 10 Hz sampling rate, to investigate the causal modulation at different
      frequencies up to 5 Hz. Using a visuomotor two-choice reaction-time task, both
      the spectral decomposition of Granger causality and isolated effective coherence
      revealed that the BOLD signal at frequency up to 3 Hz can still be used to
      estimate significant dominant directions of information flow consistent with
      results from the time-domain Granger causality analysis. We showed the
      specificity of estimated dominant directions of information flow at high
      frequencies by contrasting causality estimates using data collected during the
      visuomotor task and resting state. Our data suggest that hemodynamic responses
      carry physiological information related to inter-regional modulation at frequency
      higher than what has been commonly considered.

PMID- 26208872
TI  - Partial covariance based functional connectivity computation using Ledoit-Wolf
      covariance regularization.
AB  - Functional connectivity refers to shared signals among brain regions and is
      typically assessed in a task free state. Functional connectivity commonly is
      quantified between signal pairs using Pearson correlation. However, resting-state
      fMRI is a multivariate process exhibiting a complicated covariance structure.
      Partial covariance assesses the unique variance shared between two brain regions
      excluding any widely shared variance, hence is appropriate for the analysis of
      multivariate fMRI datasets. However, calculation of partial covariance requires
      inversion of the covariance matrix, which, in most functional connectivity
      studies, is not invertible owing to rank deficiency. Here we apply Ledoit-Wolf
      shrinkage (L2 regularization) to invert the high dimensional BOLD covariance
      matrix. We investigate the network organization and brain-state dependence of
      partial covariance-based functional connectivity. Although RSNs are
      conventionally defined in terms of shared variance, removal of widely shared
      variance, surprisingly, improved the separation of RSNs in a spring embedded
      graphical model. This result suggests that pair-wise unique shared variance plays
      a heretofore unrecognized role in RSN covariance organization. In addition,
      application of partial correlation to fMRI data acquired in the eyes open vs.
      eyes closed states revealed focal changes in uniquely shared variance between the
      thalamus and visual cortices. This result suggests that partial correlation of
      resting state BOLD time series reflect functional processes in addition to
      structural connectivity. 

PMID- 26208873
TI  - MRI compatible optrodes for simultaneous LFP and optogenetic fMRI investigation
      of seizure-like afterdischarges.
AB  - In preclinical studies, implanted electrodes can cause severe degradation of MRI
      images and hence are seldom used for chronic studies employing functional
      magnetic resonance imaging. In this study, we developed carbon fiber optrodes
      (optical fiber and electrode hybrid devices), which can be utilised in chronic
      longitudinal studies aiming to take advantage of emerging optogenetic
      technologies, and compared them with the more widely used tungsten optrodes. We
      find that optrodes constructed using small diameter (~130 MUm) carbon fiber
      electrodes cause significantly reduced artifact on functional MRI images compared
      to those made with 50 MUm diameter tungsten wire and at the same time the carbon
      electrodes have lower impedance, which leads to higher quality LFP recordings. In
      order to validate this approach, we use these devices to study optogenetically
      induced seizure-like afterdischarges in rats sedated with dexmedetomidine and
      compare these to sub (seizure) threshold stimulations in the same animals. The
      results indicate that seizure-like afterdischarges involve several
      extrahippocampal brain regions that are not recruited by subthreshold optogenetic
      stimulation of the hippocampus at 20 Hz. Subthreshold stimulation led to
      activation of the entire ipsilateral hippocampus and septum, whereas
      afterdischarges additionally produced activations in the contralateral
      hippocampal formation, neocortex, cerebellum, nucleus accumbens, and thalamus.
      Although we demonstrate just one application, given the ease of fabrication, we
      anticipate that carbon fiber optrodes could be utilised in a variety of studies
      that could benefit from longitudinal optogenetic functional magnetic resonance
      imaging. 

PMID- 26208874
TI  - Recovery of dopamine transporters with methamphetamine detoxification is not
      linked to changes in dopamine release.
AB  - Methamphetamine's widepread abuse and concerns that it might increase Parkinson's
      disease led us to assess if the reported loss of dopamine transporters (DAT) in
      methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with
      [(11)C]cocaine to measure DAT, and with [(11)C]raclopride to measure dopamine
      release (assessed as changes in specific binding of [(11)C]raclopride between
      placebo and methylphenidate), which was used as a marker of dopamine neuronal
      function, we show that MA (n=16), tested during early detoxification, had lower
      DAT (20-30%) but overall normal DA release in striatum (except for a small
      decrease in left putamen), when compared to controls (n=15). In controls, DAT
      were positively correlated with DA release (higher DAT associated with larger DA
      increases), consistent with DAT serving as markers of DA terminals. In contrast,
      MA showed a trend for a negative correlation (p=0.07) (higher DAT associated with
      lower DA increases), consistent with reduced DA re-uptake following DAT
      downregulation. MA who remained abstinent nine-months later (n=9) showed
      significant increases in DAT (20%) but methylphenidate-induced dopamine increases
      did not change. In contrast, in controls, DAT did not change when retested 9
      months later but methylphenidate-induced dopamine increases in ventral striatum
      were reduced (p=0.05). Baseline D2/D3 receptors in caudate were lower in MA than
      in controls and did not change with detoxification, nor did they change in the
      controls upon retest. The loss of DAT in the MA, which was not associated with a
      concomitant reduction in dopamine release as would have been expected if DAT loss
      reflected DA terminal degneration; as well as the recovery of DAT after
      protracted detoxification, which was not associated with increased dopamine
      release as would have been expected if DAT increases reflected terminal
      regeneration, indicate that the loss of DAT in these MA does not reflect
      degeneration of dopamine terminals.

PMID- 26208875
TI  - Foreword: "The PI3-kinase/Akt pathway: From signaling to diseases".

PMID- 26208876
TI  - Synthesis and Insecticidal Activity of Novel Nitropyridyl-Based Dichloropropene
      Ethers.
AB  - Dihalopropene ether insecticides are known for good features such as no cross
      resistance to other insecticide classes and safety for mammals. Pyridalyl is the
      only currently commercialized dichloropropene ether insecticide; however, it
      contains a trifluoromethyl group, the synthesis of which requires harsh reagents
      and reaction conditions. To search for novel dihalopropene ethers with unique
      biological activities but without trifluoromethyl groups, a series of
      nitropyridyl-based dichloropropene ether analogues were synthesized by reacting
      nitro-based halopyridine with 2,6-dichloro-4-(3,3-dichloroallyloxy)phenol or 2,6
      dichloro-4-(3,3-dichloroallyloxy)phenyl 3-hydroxypropyl ether. Bioassay showed
      that the compounds exhibited potent insecticidal activities against various
      lepidopteran pests. Particularly, 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3
      (5-nitro-2-pyridyloxy)propyl ether (8e) was active against major agricultural
      pests, and its insecticidal potency was comparable to that of Pyridalyl. Besides
      the trifluoromethyl group in Pyridalyl, a nitro group on the 5-position of the
      pyridyl ring is also viable for the development of optimal insecticidal activity.

PMID- 26208878
TI  - Distal fusion level selection in Lenke 1A curves according to axial plane
      analyses.
AB  - BACKGROUND CONTEXT: In adolescent idiopathic scoliosis (AIS), identification of
      curve patterns and determination of fusion levels are most important for
      correcting deformity, improving trunk balance, and saving motion segments. Lenke
      1A scoliosis is the most common type of AIS, accounting for around 16% of all
      AIS; however, how to determine the lower instrumented vertebrae in this common
      curve type is unclear. PURPOSE: The aim was to classify Lenke 1A curves according
      to lumbar axial plane analyses to determine optimal distal fusion level
      selection. STUDY DESIGN: This was a retrospective study. PATIENT SAMPLE: This
      study included 69 consecutive patients with AIS (13 males and 56 females) of
      Lenke Type 1A curve who underwent posterior correction and fusion of the thoracic
      spine between 2001 and 2013 in a single center. OUTCOME MEASURES: Coronal,
      sagittal, and axial parameters were measured from plain radiographs that were
      obtained at initial medical examination of the patients. METHODS: Coronal and
      sagittal plane and whole spine segmental vertebra rotations from thoracic 1 to
      lumbar 5 were evaluated by using Drerup method. As a result of analysis of axial
      plane, all patients with Lenke 1A curves were divided into three groups depending
      on lumbar vertebral rotation. In Group I, the rotation of lumbar vertebral
      rotation was accepted as neutral. In Group II, the direction of lumbar vertebral
      rotation was same with other vertebrae in the main curve. In Group III, the
      rotation of lumbar vertebral rotation had opposite direction with vertebrae in
      the main curve. RESULTS: In Group I curves, the mean position of lower end
      vertebrae (LEVs) was more frequently at T11, neutral vertebra (NV)-last touched
      vertebra (LTV) at T12, and stable vertebra (SV) at L2. In Group II curves, the
      mean position of LEV was more frequent at L1, LTV at L2, NV at L3, and SV at L4,
      whereas in Group III curves, the median position of LEV-NV-LTV was frequently at
      T12 and that of SV at L1. Then, Group I to III curves between Group II curves
      showed the gap differences of NV-LEV, SV-LEV to be significantly different.
      Similarly, the SV was not more than two segments distal from LEV in Group I and
      Group III but more than two to three segments from LEV in Group II. CONCLUSIONS:
      Our analysis suggested that not all Lenke 1A curves yield satisfactory outcome
      with the same fusion extend although a high percentage of the patients with Lenke
      1A curves have shown satisfactory outcome with NV fusion. Thus, it seems that
      some Lenke 1A curves may require fusion to SV.

PMID- 26208877
TI  - Cross-cancer profiling of molecular alterations within the human autophagy
      interaction network.
AB  - Aberrant activation or disruption of autophagy promotes tumorigenesis in various
      preclinical models of cancer, but whether the autophagy pathway is a target for
      recurrent molecular alteration in human cancer patient samples is unknown. To
      address this outstanding question, we surveyed 211 human autophagy-associated
      genes for tumor-related alterations to DNA sequence and RNA expression levels and
      examined their association with patient survival outcomes in multiple cancer
      types with sequence data from The Cancer Genome Atlas consortium. We found 3
      (RB1CC1/FIP200, ULK4, WDR45/WIPI4) and one (ATG7) core autophagy genes to be
      under positive selection for somatic mutations in endometrial carcinoma and clear
      cell renal carcinoma, respectively, while 29 autophagy regulators and pathway
      interactors, including previously identified KEAP1, NFE2L2, and MTOR, were
      significantly mutated in 6 of the 11 cancer types examined. Gene expression
      analyses revealed that GABARAPL1 and MAP1LC3C/LC3C transcripts were less abundant
      in breast cancer and non-small cell lung cancers than in matched normal tissue
      controls; ATG4D transcripts were increased in lung squamous cell carcinoma, as
      were ATG16L2 transcripts in kidney cancer. Unsupervised clustering of autophagy
      associated mRNA levels in tumors stratified patient overall survival in 3 of 9
      cancer types (acute myeloid leukemia, clear cell renal carcinoma, and head and
      neck cancer). These analyses provide the first comprehensive resource of
      recurrently altered autophagy-associated genes in human tumors, and highlight
      cancer types and subtypes where perturbed autophagy may be relevant to patient
      overall survival. 

PMID- 26208879
TI  - The impact of coronal alignment of device on radiographic degeneration in the
      case of total disc replacement.
AB  - BACKGROUND CONTEXT: Numerous studies have been conducted on the importance of
      radiographic parameters after a total disc replacement (TDR). Most of them have
      focused on sagittal alignment. There has been no research on what influence the
      coronal alignment or tilting of device has on radiographic parameters. PURPOSE:
      The aim was to investigate the influences of coronal tilting of device on
      radiographic parameters and degeneration. STUDY DESIGN/SETTING: This was a
      prospective comparative study. PATIENT SAMPLE: A total of 180 patients with
      single-level cervical disc disease who underwent TDR were included. OUTCOME
      MEASURES: Overall and functional spinal unit (FSU) sagittal range of motion
      (ROM), coronal alignment (or tilting) of device, and postoperative radiographic
      degeneration (RD) were analyzed. METHODS: Static anteroposterior, lateral X-rays,
      and dynamic lateral radiographs were assessed preoperatively, postoperatively, at
      1.5, 3, 6, 9, 12, 18, 24 months, and every 6 months thereafter until final follow
      up. A correlation with various parameters that could result in RD was
      investigated, For this, the patients were divided into two groups (Group I, RD;
      Group II, no RD) and subdivided into Group I-A (<5 degrees ; low coronal tilt)
      and Group I-B (>=5 degrees ; high coronal tilt) to analyze whether coronal
      tilting of device was correlated with RD. RESULTS: No statistical differences
      were found in preoperative overall and FSU ROM, postoperative overall and FSU ROM
      between Groups I and II. However, there was significant difference in coronal
      tilting of device between Groups I (4.50+/-2.83 degrees ) and II (2.04+/-1.15
      degrees ; p=.001). There were no significant differences in preoperative overall
      and FSU ROM, postoperative overall and FSU ROM between Group I-A and I-B. But, RD
      incidence rate at surgical segment in Group I-A was 23.1%, whereas that in Group
      I-B was 75.0% (p=.001). The influence level of a difference in the incidence rate
      was found to be 10.0 of the odds ratio. Radiographic degeneration incidence rate
      at adjacent levels in Group I-A was 8.33%, whereas that in Group I-B was 25.0%
      (p=.013). The influence level of a difference in the incidence rate was found to
      be 3.67 of the odds ratio. CONCLUSIONS: It is considered that maintaining
      appropriate coronal alignment of device is important in long-term success after a
      cervical TDR.

PMID- 26208880
TI  - C5 palsy after cervical laminectomy and fusion: does width of laminectomy matter?
AB  - BACKGROUND CONTEXT: A common complication of cervical laminectomy and fusion with
      instrumentation (CLFI) is development of postoperative C5 nerve palsy. A proposed
      etiology is excess nerve tension from posterior drift of the spinal cord after
      decompression. We hypothesize that laminectomy width will be significantly
      increased in patients with C5 palsy and will correlate with palsy severity.
      PURPOSE: The purposes of this study were to evaluate laminectomy width as a risk
      factor for C5 palsy and to assess correlation with palsy severity. STUDY
      DESIGN/SETTING: This is a retrospective, single-institution clinical study.
      PATIENT SAMPLE: Patient population included all patients with cervical
      spondylotic myelopathy who underwent CLFI between 2007 and 2014 by a single
      surgeon. Patients who underwent CLFI for trauma, infection, or tumor or had
      previous or circumferential cervical surgery were excluded. All patients with a
      new C5 palsy received a postoperative magnetic resonance imaging. An additional
      computed tomography (CT) scan was ordered to assess hardware. All control
      patients received a CT scan at 6 months postoperatively to evaluate fusion.
      OUTCOME MEASURES: The association between width of laminectomy and development of
      postopeative C5 palsy was measured. METHODS: Patient comorbidities including
      obesity, smoking history, and diabetes were recorded in addition to preopertaive
      and postoperative deltoid and biceps motor strength. Sagittal alignment was
      measured with C2-C7 Cobb angle preopertaive and postoperative radiographs. The
      width of laminectomy was measured in a blinded fashion on the postoperative CT
      scan by two observers. RESULTS: Seventeen patients with C5 nerve palsy and 12
      controls were identified. There were no baseline differences in age, sex,
      diabetes, smoking history, number of surgical levels, or sagittal alignment. Body
      mass index was significantly higher in the control cohort. There was no
      significant increase in the C3-C7 laminectomy width in patients with
      postoperative C5 palsy. The width of laminectomy measurments were highly similar
      between the two observers. There was no correlation between laminectomy width and
      palsy severity. CONCLUSIONS: This is the largest series of C5 palsies after
      laminectomy documented with CT imaging. Laminectomy width was not associated with
      an increased risk of postoperative C5 palsy at any level. Reduction in
      laminectomy width may not reduce rate of postoperative nerve palsy.

PMID- 26208882
TI  - The loss of NDRG2 expression improves depressive behavior through increased
      phosphorylation of GSK3beta.
AB  - N-myc downstream-regulated gene 2 (NDRG2) is one of the important stress
      inducible genes and plays a critical role in negatively regulating PI3K/AKT
      signaling during hypoxia and inflammation. Through recruitment of PP2A
      phosphatase, NDRG2 maintains the dephosphorylated status of PTEN to suppress
      excessive PI3K/AKT signaling, and loss of NDRG2 expression is frequently seen in
      various types of cancer with enhanced activation of PI3K/AKT signaling. Because
      NDRG2 is highly expressed in the nervous system, we investigated whether NDRG2
      plays a functional role in the nervous system using Ndrg2-deficient mice. Ndrg2
      deficient mice do not display any gross abnormalities in the nervous system, but
      they have a diminished behavioral response associated with anxiety. Ndrg2
      deficient mice exhibited decreased immobility and increased head-dipping and
      rearing behavior in two behavioral models, indicating an improvement of emotional
      anxiety-like behavior. Moreover, treatment of wild-type mice with the
      antidepressant drug imipramine reduced the expression of Ndrg2 in the frontal
      cortex, which was due to the degradation of HIF-1alpha through reduced expression
      of HSP90 protein. Furthermore, we found that the down-regulation of Ndrg2 in
      Ndrg2-deficient mice and imipramine treatment improved mood behavior with
      enhanced phosphorylation of GSK3beta through activation of PI3K/AKT signaling,
      suggesting that the expression level of NDRG2 has a causal influence on mood
      related phenotypes. Collectively, these results suggest that NDRG2 may be a
      potential target for mood disorders such as depression and anxiety. 

PMID- 26208883
TI  - Differentiation and apoptosis induction by lovastatin and gamma-tocotrienol in HL
      60 cells via Ras/ERK/NF-kappaB and Ras/Akt/NF-kappaB signaling dependent down
      regulation of glyoxalase 1 and HMG-CoA reductase.
AB  - Glyoxalase 1 (GLO1) and HMG-CoA reductase (HMGCR) are highly expressed in most
      tumor cells and little in normal cells. In this study, treatment of HL-60 cells
      with lovastatin induced characteristic apoptosis in a dose-dependent manner. We
      demonstrated that lovastatin treatment inhibited Ras and Raf protein
      translocation to cell membrane and eliminated the phosphorylation of the
      downstream effectors Akt and ERK, and the subsequent NF-kappaB translocation into
      nucleus. Specific inhibitors and gamma-tocotrienol confirmed the Ras/Raf/ERK/NF
      kappaB/GLO1 and Ras/Akt/NF-kappaB/GLO1 pathways. Data revealed that lovastatin
      induced HL-60 cell death was attenuated by mevalonate treatment. We demonstrated
      also that gamma-tocotrienol showed its apoptotic effect on the HL-60 cell through
      the same pathway. gamma-Tocotrienol enhanced the apoptotic effect of lovastatin
      through the down-regulation of GLO1 and HMGCR resulting in an increase of
      methylglyoxal and a decrease of cholesterol and led to the apoptosis of HL-60
      cells. Data also revealed that both lovastatin and gamma-tocotrienol induced
      significant HL-60 cell differentiation. These results suggest that both
      lovastatin and gamma-tocotrienol could induce differentiation and followed by
      apoptosis. 

PMID- 26208881
TI  - Mechanisms of Evolutionary Innovation Point to Genetic Control Logic as the Key
      Difference Between Prokaryotes and Eukaryotes.
AB  - The evolution of life from the simplest, original form to complex, intelligent
      animal life occurred through a number of key innovations. Here we present a new
      tool to analyze these key innovations by proposing that the process of
      evolutionary innovation may follow one of three underlying processes, namely a
      Random Walk, a Critical Path, or a Many Paths process, and in some instances may
      also constitute a "Pull-up the Ladder" event. Our analysis is based on the
      occurrence of function in modern biology, rather than specific structure or
      mechanism. A function in modern biology may be classified in this way either on
      the basis of its evolution or the basis of its modern mechanism. Characterizing
      key innovations in this way helps identify the likelihood that an innovation
      could arise. In this paper, we describe the classification, and methods to
      classify functional features of modern organisms into these three classes based
      on the analysis of how a function is implemented in modern biology. We present
      the application of our categorization to the evolution of eukaryotic gene
      control. We use this approach to support the argument that there are few, and
      possibly no basic chemical differences between the functional constituents of the
      machinery of gene control between eukaryotes, bacteria and archaea. This suggests
      that the difference between eukaryotes and prokaryotes that allows the former to
      develop the complex genetic architecture seen in animals and plants is something
      other than their chemistry. We tentatively identify the difference as a
      difference in control logic, that prokaryotic genes are by default 'on' and
      eukaryotic genes are by default 'off.' The Many Paths evolutionary process
      suggests that, from a 'default off' starting point, the evolution of the genetic
      complexity of higher eukaryotes is a high probability event. 

PMID- 26208885
TI  - Non-classical testosterone signaling in spermatogenic GC-2 cells is mediated
      through ZIP9 interacting with Gnalpha11.
AB  - Although classical and non-classical signaling of testosterone has been
      documented in several investigations, the nature of the receptor involved in the
      non-classical pathway remains a source of controversy. While some investigators
      favor the exclusive participation of the cytosolic/nuclear androgen receptor (AR)
      in both pathways, others propose a membrane-bound receptor as the mediator of the
      non-classical testosterone signaling. Evidence is provided here that in the
      spermatogenic cell line GC-2 the non-classical signaling pathway of testosterone,
      characterized through the activation of Erk1/2 and transcription factors like
      CREB or ATF-1, is not mediated through the classical nuclear androgen receptor
      (AR) but rather by a membrane-associated receptor. This receptor is ZIP9, a
      Zn(2+) transporter from the family of the ZRT, IRT-like proteins (ZRT=zinc
      regulated transporter; IRT=iron-regulated transporter), which directly interacts
      with the G-protein Gnalpha11. siRNA-induced abrogation of the expression of
      either of these two proteins, whose close contacts are demonstrated by an in situ
      proximity assay, completely prevents all non-classical signaling effects of
      testosterone addressed. In contrast, silencing of AR expression does not
      influence the same signaling events. The identification of ZIP9/Gnalpha11
      interactions as the mediators of the non-classical testosterone signaling cascade
      in spermatogenic GC-2 cells might help to supplement our knowledge concerning the
      role of testosterone in male fertility and reproduction. 

PMID- 26208884
TI  - MEK1 dependent and independent ERK activation regulates IL-10 and IL-12
      production in bone marrow derived macrophages.
AB  - The mitogen activated protein kinases ERK1/2 play an important role in response
      to toll like receptor (TLR) activation and cytokine production, including IL-10
      and IL-12. Here, we examined the role of MEK1 in ERK1/2 activation in response to
      TLR4 agonist by using bone marrow-derived macrophages (BMDMs) from wild type (WT)
      and Mek1(d/d)Sox2(Cre) mice. Our data demonstrates that MEK1 is essential for
      ERK1/2 activation in response to LPS. Furthermore, stimulation of the TLR4
      receptor of BMDMs derived from Mek1(d/d)Sox2(Cre) mice showed enhanced STAT4
      phosphorylation and increased IL-12 secretion, but exhibited a significantly
      lower IL-10 production as compared to WT macrophages. Most interestingly, TLR
      ligation in the presence of recombinant IL-10 (rIL-10) or retinoic acid (RA) led
      to ERK1/2 activation independent of MEK1 in BMDMs derived from Mek1(d/d)Sox2(Cre)
      mice and led to inhibition of STAT4 and decreased IL-12 levels. Collectively,
      these data suggest that MEK1 is required for TLR4 mediated ERK activation and in
      turn regulates the production of IL-10 and IL-12. It also indicates that ERK1/2
      can be activated independent of MEK1 in the presence of IL-10 and RA and this
      activation negatively regulates IL-12, but positively regulates IL-10 production.
      These findings may have significant implications for the development of drugs
      that modulate MEK1 activity in the treatment of inflammatory, autoimmune and
      proliferative diseases such as cancer. 

PMID- 26208886
TI  - Arterioportal fistula, a rare cause of presinusoidal portal hypertension.

PMID- 26208888
TI  - Assessing clinical assessment tools for older adults.

PMID- 26208887
TI  - Discovery and optimization of a highly efficacious class of 5-aryl-2
      aminopyridines as FMS-like tyrosine kinase 3 (FLT3) inhibitors.
AB  - Based on a putative binding mode of quizartinib (AC220, 1), a potent FMS-like
      tyrosine kinase 3 (FLT3) inhibitor in Phase III clinical development, we have
      designed de novo a simpler aminopyridine-based hinge binding motif. Further
      optimization focusing on maximizing in vivo efficacy and minimizing CYP3A4 time
      dependent inhibition resulted in a highly efficacious compound (6s) in tumor
      xenograft model for further preclinical development. 

PMID- 26208889
TI  - Methyl jasmonate and its potential in cancer therapy.
AB  - Methyl jasmonate (MeJa) is a naturally occurring hydrophobic oxylipin
      phytohormone. Early findings obtained from cancer cell lines suggest that MeJa is
      endowed with anticancer capabilities. It has been recently proposed that MeJa
      represents a novel agent that exhibits direct and selective actions against tumor
      cells without affecting normal human cells. In a previous study, I reported that
      MeJa itself is enough to result in the dysfunction of mitochondria and
      chloroplasts, as well as to activate cell death program (apoptosis), in the
      normal protoplasts of Arabidopsis thaliana. Indeed, this also holds true for
      other living plant systems in which senescence, hypersensitive response and
      oxidative stress have been found under MeJa action. Therefore, in this addendum
      to my previous article, I would like to stress that much more attention should be
      paid to the potential effect(s) of MeJa, or its derivatives, on healthy cells and
      tissues before it is used for clinical anticancer drugs, whether being used alone
      or in combination with other agents. 

PMID- 26208890
TI  - Influence of diabetes on survival in patients with cystic fibrosis before and
      after lung transplantation.
AB  - BACKGROUND: The influence of diabetes mellitus (DM) on survival in patients with
      cystic fibrosis (CF) before and after lung transplantation is not well studied.
      METHODS: To determine the influence of DM in patients with CF, the United Network
      for Organ Sharing database (2005-2013) was queried for 2 cohorts: first-time lung
      transplant candidates who were not transplanted and first-time transplant
      recipients. RESULTS: A total of 679 patients with CF had data on DM status at
      listing and did not undergo transplantation. In this cohort, DM was associated
      with significant increase in mortality hazard as shown by an adjusted
      multivariate Cox model fitted to the whole cohort (hazard ratio [HR], 1.4; 95%
      confidence interval [CI], 1.1-1.8; P = .012) and by a Cox model stratified on
      pairs of DM and non-DM patients matched on the propensity of having DM at listing
      (HR, 1.9; 95% CI, 1.2-2.9; P = .003). In comparison, a total of 1464 patients
      with CF had data on DM status at listing and received a transplant, but DM at
      listing was not associated with posttransplant survival. The lack of association
      between DM and mortality hazard was evident in a multivariate Cox regression
      model fitted to the whole sample (HR, 1.0; 95% CI, 0.82-1.2; P = .98) and a Cox
      regression model stratified on matched pairs of DM and non-DM patients (HR, 1.1;
      95% CI, 0.82-1.5; P = .56). CONCLUSIONS: The presence of DM is associated with
      significantly increased risk for death in patients with CF on the wait list
      before lung transplantation, but does not influence survival after
      transplantation.

PMID- 26208891
TI  - What is the best second conduit for coronary artery bypass grafting? With no
      silver bullet study we should not ignore good regular bullets when we get them!

PMID- 26208892
TI  - High-speed visualization of disturbed pathlines in axial flow ventricular assist
      device under pulsatile conditions.
AB  - OBJECTIVE: To investigate potentially prothrombotic flow patterns within an axial
      flow ventricular assist device under clinically relevant pulsatile hemodynamic
      conditions. METHODS: A transparent replica of the HeartMate-II left ventricular
      assist device (Thoratec, Pleasanton, Calif) was visualized using a high speed
      camera at both low and high frame rates (125 and 3000 fps). Three steady-state
      conditions were studied: nominal (4.5 lpm), low flow (3.0 lpm), and high flow
      (6.0 lpm). Time-varying conditions were introduced with an external pulsatile
      pump that modulated the flow rate by approximately +/- 50% of the mean,
      corresponding to a pulsatility index of 1.0. RESULTS: At nominal and high flow
      rates, the path lines within the upstream region were generally stable, well
      attached, and streamlined. As the flow rate was reduced below 3.8 lpm, a rapid
      transition to a chaotic velocity field occurred, exhibiting a large toroidal
      vortex adjacent to the upstream bearing. The pathlines in the downstream stator
      section were consistently chaotic for all hemodynamic conditions investigated. It
      was common to observe tracer particles trapped within recirculation bubbles and
      drawn retrograde, causing repeated contact with the bearing surfaces. The
      addition of pulsatility caused the flow field to become periodically chaotic
      during the diastolic portion of the cardiac cycle depending on the instantaneous
      flow rate and acceleration. CONCLUSIONS: The contribution of pulsatility by the
      native heart may induce a periodic disturbance to an otherwise stable flow field
      within an axial flow ventricular assist device, particularly during the diastolic
      and decelerating portion of the cardiac cycle. Potentially prothrombotic flow
      features were found to occur periodically in the region of the upstream bearing.

PMID- 26208893
TI  - Investigating the feasibility and acceptability of health psychology-informed
      obesity training for medical students.
AB  - Health psychologists have succeeded in identifying theory-congruent behaviour
      change techniques (BCTs) to prevent and reduce lifestyle-related illnesses, such
      as cardiovascular disease, cancers and diabetes. Obesity management discussions
      between doctors and patients can be challenging and are often avoided. Despite a
      clear training need, it is unknown how best to tailor BCT research findings to
      inform obesity-management training for future healthcare professionals. The
      primary objective of this descriptive study was to gather information on the
      feasibility and acceptability of delivering and evaluating health psychology
      informed obesity training to UK medical students. Medical students (n = 41)
      attended an obesity management session delivered by GP tutors. Sessions were
      audio-recorded to enable fidelity checks. Acceptability of training was explored
      qualitatively. Tutors consistently delivered training according to the
      intervention protocol; and students and tutors found the training highly
      acceptable. This psychology-informed training can be delivered successfully by GP
      tutors and further research is warranted to explore its efficacy. 

PMID- 26208894
TI  - Serologic assay for diagnosis of celiac disease based on a patient-derived
      monoclonal antigliadin antibody.
AB  - BACKGROUND & AIMS: Patients with celiac disease can be identified based on the
      detection of serum antibodies to deamidated gliadin peptides (DGPs). Recombinant
      human monoclonal antibodies (hmAb) against gliadin are produced by cloning
      antibody genes from single IgA-producing plasma cells isolated from lesions of
      patients with celiac disease. We developed an assay to identify patients with
      celiac disease based on the ability of antibodies from their serum to inhibit the
      binding of a gliadin-specific hmAb (1002-1E03) to a specific peptide antigen
      (inhibition assay). METHODS: We selected 2 peptides (a 34-mer and a 26-mer) found
      in omega-gliadins and low-molecular-weight glutenins that had been identified as
      specific targets of the hmAb 1002-1E03 from a digest of gliadin treated by
      transglutaminase 2. These peptides contained repeat sequence motifs; their
      interaction with hmAb 1002-1E03 was assessed in an amplified luminescent
      proximity homogeneous inhibition assay. We also tested peptides we created that
      included 3 repeated sequence motifs. Serum samples from untreated patients
      diagnosed with celiac disease (n = 106) and 2 control groups (198 blood donors,
      151 patients with Crohn's disease) were analyzed using the assay, as well as in
      conventional commercial assays that measure IgA against transglutaminase 2 (TG2)
      or IgG against DGP. RESULTS: In our inhibition assays, the 34-mer peptide showed
      the best results, and identified patients with celiac disease with 86.8%
      sensitivity and 98.6% specificity. Its diagnostic accuracy was comparable with
      that of commercial anti-DGP IgG (sensitivity, 87.9%; specificity, 98.0) and anti
      TG2 IgA (sensitivity, 81.1%; specificity, 98.9) assays, and it detected most of
      the patients with anti-TG2 IgA-negative celiac disease without a significant
      decrease in specificity. Combined use of the anti-omega34 and the anti-TG2 assays
      produced specificity and sensitivity values of 95.3% and 98.0%, respectively.
      CONCLUSIONS: We developed an antigliadin inhibition assay that identifies
      patients with celiac disease with high levels of specificity and sensitivity. It
      may prove useful as an adjunct to the current assay for anti-TG2 IgA.

PMID- 26208896
TI  - Statin use reduces risk of esophageal adenocarcinoma in US veterans with
      Barrett's esophagus: a nested case-control study.
AB  - BACKGROUND & AIMS: Statins have been reported to protect against esophageal
      adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). However, there
      are few data from adequately powered cohort studies of subjects with BE. METHODS:
      We conducted a nested case-control study of a cohort of BE patients identified
      from national Veteran Affairs (VA) outpatient files, diagnosed with BE from 2004
      through 2009. New cases of EAC recorded after BE diagnosis were identified during
      a follow-up period that ended in 2011 and verified using electronic medical
      records. We selected patients with BE without EAC (controls) using incidence
      density sampling; 3 controls were matched to each case based on birth year and
      date of BE diagnosis. Our analysis included only male patients with at least 1 VA
      visit per year of follow up. We identified prescriptions for statins and non
      statin lipid lowering medications filled after BE diagnosis and up to 90 days
      before EAC diagnosis for cases and controls (during the corresponding time
      period); we examined the association between statin use and EAC in conditional
      logistic regression models. RESULTS: We compared 311 EAC cases to 856 controls.
      Cases were less likely to use any statins than controls (40.2% vs 54.0%; P <
      .01). Significantly lower proportions of cases used statins for 6-18 months
      (10.0% cases vs 17.1% controls) and >18 months (19.3% vs 24.0%, respectively; P <
      .01). Simvastatin was the most commonly prescribed statin (accounting for 86.9%
      of statin use); the defined daily dose of simvastatin was lower in cases than in
      controls (21-40 mg/day, 9.3% vs 14.5%, respectively; and >40 mg/day, 8.4% vs
      12.6%, respectively; P < .01). In multivariate analysis, statin use was inversely
      associated with development of EAC (adjusted odds ratio [OR], 0.65; 95%
      confidence interval [CI], 0.47-0.91). This protective association was strongest
      for patients with advanced-stage EAC: in a stratified analysis, comparison of 189
      cases with stage 0-1 EAC to 520 controls produced an adjusted OR of 0.85 (95% CI,
      0.54-1.33). Among patients with late-stage EAC (stages 2-4, n = 106) and 291
      controls, the adjusted OR was 0.44 (95% CI, 0.25-0.79). We found no association
      between EAC and non-statin lipid-lowering medications. CONCLUSIONS: In a case
      control study of US veterans, statin use among those with BE appeared to decrease
      the risk of EAC. This protective effect was strongest against advanced-stage EAC,
      and increased with statin dose.

PMID- 26208895
TI  - Genetic Insights in Barrett's Esophagus and Esophageal Adenocarcinoma.
AB  - Beginning in the 1980s, an alarming rise in the incidence of esophageal
      adenocarcinoma (EA) led to screening of patients with reflux to detect Barrett's
      esophagus (BE) and surveillance of BE to detect early EA. This strategy, based on
      linear progression disease models, resulted in selective detection of BE that
      does not progress to EA over a lifetime (overdiagnosis) and missed BE that
      rapidly progresses to EA (underdiagnosis). Here we review the historical thought
      processes that resulted in this undesired outcome and the transformation in our
      understanding of genetic and evolutionary principles governing neoplastic
      progression that has come from application of modern genomic technologies to
      cancers and their precursors. This new synthesis provides improved strategies for
      prevention and early detection of EA by addressing the environmental and
      mutational processes that can determine "windows of opportunity" in time to
      detect rapidly progressing BE and distinguish it from slowly or nonprogressing
      BE. 

PMID- 26208898
TI  - Effect of sparteine on status epilepticus induced in rats by pentylenetetrazole,
      pilocarpine and kainic acid.
AB  - The long-term effects of status epilepticus (SE) include severe clinical
      conditions that result in disorders of various organs and systems as well as
      neurological damage that could lead to death. Sparteine is a quinolizidine
      alkaloid synthesized from most Lupine species, and its anticonvulsive effect was
      evaluated in the pentylenetetrazole model of SE. However, efforts to clearly
      determine the anticonvulsive effect of sparteine have not been made previously.
      For this reason, we consider it important to study the anticonvulsant effects of
      sparteine at the level of behavior and EEG activity in three different SE models.
      The animals of the control groups, which received intraperitoneal
      pentylenetetrazole (90 mg/kg), kainic acid (9 mg/kg) or pilocarpine (370 mg/kg),
      exhibited convulsive behavior and epileptiform activity. After sparteine
      pretreatment (13 mg/kg, administered 30 min before the convulsive drug), the
      animals administered pentylenetetrazole and pilocarpine exhibited reduced
      mortality rates compared with the corresponding control groups, while the animals
      administered kainic acid exhibited a delayed onset of convulsive behavior and
      decreased seizure duration compared with the corresponding control group. In the
      three models of SE, a significant reduction in the amplitude and frequency of
      discharge trains was observed. These results support the anticonvulsant effect of
      low doses of sparteine and allow us to direct our efforts to other new
      anticonvulsant strategies for seizure treatment. However, it is necessary to
      perform more experiments to determine the precise mechanism through which
      sparteine produces an anticonvulsant effect at this concentration.

PMID- 26208897
TI  - Depletion of macrophages in CD11b diphtheria toxin receptor mice induces brain
      inflammation and enhances inflammatory signaling during traumatic brain injury.
AB  - Immune cells have important roles during disease and are known to contribute to
      secondary, inflammation-induced injury after traumatic brain injury. To delineate
      the functional role of macrophages during traumatic brain injury, we depleted
      macrophages using transgenic CD11b-DTR mice and subjected them to controlled
      cortical impact. We found that macrophage depletion had no effect on lesion size
      assessed by T2-weighted MRI scans 28 days after injury. Macrophage depletion
      resulted in a robust increase in proinflammatory gene expression in both the
      ipsilateral and contralateral hemispheres after controlled cortical impact.
      Interestingly, this sizeable increase in inflammation did not affect lesion
      development. We also showed that macrophage depletion resulted in increased
      proinflammatory gene expression in the brain and kidney in the absence of injury.
      These data demonstrate that depletion of macrophages in CD11b-DTR mice can
      significantly modulate the inflammatory response during brain injury without
      affecting lesion formation. These data also reveal a potentially confounding
      inflammatory effect in CD11b-DTR mice that must be considered when interpreting
      the effects of macrophage depletion in disease models.

PMID- 26208899
TI  - Training Vegetable Parenting Practices Through a Mobile Game: Iterative
      Qualitative Alpha Test.
AB  - BACKGROUND: Vegetable consumption protects against chronic diseases, but many
      young children do not eat vegetables. One quest within the mobile application
      Mommio was developed to train mothers of preschoolers in effective vegetable
      parenting practices, or ways to approach getting their child to eat and enjoy
      vegetables. A much earlier version of the game, then called Kiddio, was alpha
      tested previously, but the game has since evolved in key ways. OBJECTIVE: The
      purpose of this research was to alpha test the first quest, substantiate earlier
      findings and obtain feedback on new game features to develop an effective,
      compelling parenting game. METHODS: Mothers of preschool children (n=20) played a
      single quest of Mommio 2 to 4 times, immediately after which a semi-structured
      interview about their experience was completed. Interviews were transcribed and
      double coded using thematic analysis methods. RESULTS: Mothers generally liked
      the game, finding it realistic and engaging. Some participants had difficulties
      with mechanics for moving around the 3-D environment. Tips and hints were well
      received, and further expansion and customization were desired. CONCLUSIONS:
      Earlier findings were supported, though Mommio players reported more enjoyment
      than Kiddio players. Continued development will include more user-friendly
      mechanics, customization, opportunities for environment interaction, and food
      parenting scenarios.

PMID- 26208900
TI  - Institutional Bereavement Care for Fictive Kin: Staff Grief in CCRCs.
AB  - PURPOSE: The purpose of this study was to explore approaches used by
      administrators to respond to grief and bereavement among staff after the death of
      a resident. METHODS: Continuing care retirement community (CCRC) facilities (n =
      10) were randomly selected from a larger study of 31 facilities. Open-ended
      interviews were conducted using a structured interview protocol. Qualitative
      methods, specifically thematic analysis, were used to analyze the interview data.
      FINDINGS: Emergent themes suggest that LTC facilities have freedom in how to
      provide support for staff members, family members, and other residents after the
      death of a loved one. However, results show variations in methods for notifying
      staff of a resident's death, inclusion of direct care staff in caring for the
      deceased, providing memorial services, and offering grief/bereavement support.
      When speaking of the loss of a resident and ways to provide grief/bereavement
      support, only 3 of the 10 administrators discussed the importance of extending
      such services to the staff. IMPLICATIONS: Causes of staff burnout in the CCRC
      workplace is an unresolved issue. Research has shown that inadequate grief and
      bereavement support for staff contributes to factors associated with staff
      burnout and retention. Although administrators hold formal services after a
      resident has died, there are differences among facilities. It may be that
      organizations could improve bereavement services for staff.

PMID- 26208901
TI  - A Threshold Level of Intratumor CD8+ T-cell PD1 Expression Dictates Therapeutic
      Response to Anti-PD1.
AB  - Despite successes, thus far, a significant proportion of the patients treated
      with anti-PD1 antibodies have failed to respond. We use mouse tumor models of
      anti-PD1 sensitivity and resistance and flow cytometry to assess tumor
      infiltrating immune cells immediately after therapy. We demonstrate that the
      expression levels of T-cell PD1 (PD1(lo)), myeloid, and T-cell PDL1 (PDL1(hi)) in
      the tumor microenvironment inversely correlate and dictate the efficacy of anti
      PD1 mAb and function of intratumor CD8(+) T cells. In sensitive tumors, we reveal
      a threshold for PD1 downregulation on tumor-infiltrating CD8(+) T cells below
      which the release of adaptive immune resistance is achieved. In contrast, PD1(hi)
      T cells in resistant tumors fail to be rescued by anti-PD1 therapy and remain
      dysfunctional unless intratumor PDL1(lo) immune cells are targeted. Intratumor
      Tregs are partly responsible for the development of anti-PD1-resistant tumors and
      PD1(hi) CD8(+) T cells. Our analyses provide a framework to interrogate
      intratumor CD8(+) T-cell PD1 and immune PDL1 levels and response in human cancer.

PMID- 26208902
TI  - IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells
      and Eliciting Tumorigenic Neutrophils Recruitment.
AB  - The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated
      with increased IL17 levels. Studying the role of IL17 in invasive breast tumor
      pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes
      produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor
      growth and prevented the migration of neutrophils and tumor cells to secondary
      disease sites. Tumorigenic neutrophils promote disease progression, producing
      CXCL1, MMP9, VEGF, and TNFalpha, and their depletion suppressed tumor growth.
      IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring
      the recruitment and differentiation of Th17. In addition, IL17A changed the gene
      expression profile and the behavior of nonmetastatic tumor cells, causing tumor
      growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17
      expression was associated with lower disease-free survival and worse prognosis in
      IDC patients. Thus, IL17 blockade represents an attractive approach for the
      control of invasive breast tumors.

PMID- 26208903
TI  - Maspin Expression in Prostate Tumor Cells Averts Stemness and Stratifies Drug
      Sensitivity.
AB  - Future curative cancer chemotherapies have to overcome tumor cell heterogeneity
      and plasticity. To test the hypothesis that the tumor suppressor maspin may
      reduce microenvironment-dependent prostate tumor cell plasticity and thereby
      modulate drug sensitivity, we established a new schematic combination of two
      dimensional (2D), three-dimensional (3D), and suspension cultures to enrich
      prostate cancer cell subpopulations with distinct differentiation potentials. We
      report here that depending on the level of maspin expression, tumor cells in
      suspension and 3D collagen I manifest the phenotypes of stem-like and dormant
      tumor cell populations, respectively. In suspension, the surviving maspin
      expressing tumor cells lost the self-renewal capacity, underwent senescence, lost
      the ability to dedifferentiate in vitro, and failed to generate tumors in vivo.
      Maspin-nonexpressing tumor cells that survived the suspension culture in compact
      tumorspheres displayed a higher level of stem cell marker expression, maintained
      the self-renewal capacity, formed tumorspheres in 3D matrices in vitro, and were
      tumorigenic in vivo. The drug sensitivities of the distinct cell subpopulations
      depend on the drug target and the differentiation state of the cells. In 2D,
      docetaxel, MS275, and salinomycin were all cytotoxic. In suspension, while MS275
      and salinomycin were toxic, docetaxel showed no effect. Interestingly, cells
      adapted to 3D collagen I were only responsive to salinomycin. Maspin expression
      correlated with higher sensitivity to MS275 in both 2D and suspension and to
      salinomycin in 2D and 3D collagen I. Our data suggest that maspin reduces
      prostate tumor cell plasticity and enhances tumor sensitivity to salinomycin,
      which may hold promise in overcoming tumor cell heterogeneity and plasticity.

PMID- 26208904
TI  - KAT6B Is a Tumor Suppressor Histone H3 Lysine 23 Acetyltransferase Undergoing
      Genomic Loss in Small Cell Lung Cancer.
AB  - Recent efforts to sequence human cancer genomes have highlighted that point
      mutations in genes involved in the epigenetic setting occur in tumor cells. Small
      cell lung cancer (SCLC) is an aggressive tumor with poor prognosis, where little
      is known about the genetic events related to its development. Herein, we have
      identified the presence of homozygous deletions of the candidate histone
      acetyltransferase KAT6B, and the loss of the corresponding transcript, in SCLC
      cell lines and primary tumors. Furthermore, we show, in vitro and in vivo, that
      the depletion of KAT6B expression enhances cancer growth, while its restoration
      induces tumor suppressor-like features. Most importantly, we demonstrate that
      KAT6B exerts its tumor-inhibitory role through a newly defined type of histone H3
      Lys23 acetyltransferase activity.

PMID- 26208905
TI  - Metastatic Competence Can Emerge with Selection of Preexisting Oncogenic Alleles
      without a Need of New Mutations.
AB  - Several experimental models faithfully recapitulate many important facets of
      human metastatic disease. Here, we have performed whole-exome sequencing in five
      widely used experimental metastasis models that were independently derived
      through in vivo selection from heterogeneous human cancer cell lines. In addition
      to providing an important characterization of these model systems, our study
      examines the genetic evolution of metastatic phenotypes. We found that in vivo
      selected highly metastatic cell populations showed little genetic divergence from
      the corresponding parental population. However, selection of genetic variations
      that preexisted in parental populations, including the well-established oncogenic
      mutations KRAS(G13D) and BRAF(G464V), was associated with increased metastatic
      capability. Conversely, expression of the wild-type BRAF allele in metastatic
      cells inhibited metastatic outgrowth as well as tumor initiation in mice. Our
      findings establish that metastatic competence can arise from heterogeneous cancer
      cell populations without the need for acquisition of additional mutations and
      that such competence can benefit from further selection of tumor-initiating
      mutations that seed primary tumorigenesis.

PMID- 26208906
TI  - TANRIC: An Interactive Open Platform to Explore the Function of lncRNAs in
      Cancer.
AB  - Long noncoding RNAs (lncRNA) have emerged as essential players in cancer biology.
      Using recent large-scale RNA-seq datasets, especially those from The Cancer
      Genome Atlas (TCGA), we have developed "The Atlas of Noncoding RNAs in Cancer"
      (TANRIC; http://bioinformatics.mdanderson.org/main/TANRIC:Overview), a user
      friendly, open-access web resource for interactive exploration of lncRNAs in
      cancer. It characterizes the expression profiles of lncRNAs in large patient
      cohorts of 20 cancer types, including TCGA and independent datasets (>8,000
      samples overall). TANRIC enables researchers to rapidly and intuitively analyze
      lncRNAs of interest (annotated lncRNAs or any user-defined ones) in the context
      of clinical and other molecular data, both within and across tumor types. Using
      TANRIC, we have identified a large number of lncRNAs with potential biomedical
      significance, many of which show strong correlations with established therapeutic
      targets and biomarkers across tumor types or with drug sensitivity across cell
      lines. TANRIC represents a valuable tool for investigating the function and
      clinical relevance of lncRNAs in cancer, greatly facilitating lncRNA-related
      biologic discoveries and clinical applications.

PMID- 26208907
TI  - STAT3 Inhibition Enhances the Therapeutic Efficacy of Immunogenic Chemotherapy by
      Stimulating Type 1 Interferon Production by Cancer Cells.
AB  - STAT3 is an oncogenic transcription factor with potent immunosuppressive
      functions. We found that pharmacologic inhibition of STAT3 or its selective
      knockout in cancer cells improved the tumor growth-inhibitory efficacy of
      anthracycline-based chemotherapies. This combined effect of STAT3
      inhibition/depletion and anthracyclines was only found in tumors growing on
      immunocompetent (not in immunodeficient) mice. As compared with Stat3-sufficient
      control tumors, Stat3(-/-) cancer cells exhibited an increased infiltration by
      dendritic cells and cytotoxic T lymphocytes after chemotherapy. Anthracyclines
      are known to induce several stress pathways that enhance the immunogenicity of
      dying and dead cancer cells, thereby stimulating a dendritic cell-dependent and T
      lymphocyte-mediated anticancer immune response. Among these therapy-relevant
      stress pathways, Stat3(-/-) cancer cells manifested one significant improvement,
      namely an increase in the expression of multiple type-1 interferon-responsive
      genes, including that of the chemokines Cxcl9 and Cxcl10. This enhanced type-1
      interferon response could be suppressed by reintroducing wild-type Stat3 (but not
      a transactivation-deficient mutant Stat3(Y705F)) into the tumor cells. This
      maneuver also abolished the improved chemotherapeutic response of Stat3(-/-)
      cancers. Finally, the neutralization of the common type-1 interferon receptor or
      that of the chemokine receptor CXCR3 (which binds CXCL9 and CXCL10) abolished the
      difference in the chemotherapeutic response between Stat3(-/-) and control
      tumors. Altogether, these results suggest that STAT3 inhibitors may improve the
      outcome of chemotherapy by enhancing the type-1 interferon response of cancer
      cells.

PMID- 26208908
TI  - Smell differential reactivity, but not taste differential reactivity, is related
      to food neophobia in toddlers.
AB  - Previous research has identified relationships between chemosensory reactivity
      and food neophobia in children. However, most studies have investigated this
      relationship using declarative data and without separately analysing smell and
      taste reactivity. Our first objective was to assess the relationships between
      smell and taste differential reactivity in toddlers (i.e. reactivity towards
      several stimuli), using experimental behavioural measurements. The second
      objective was to determine the relationships between smell (or taste)
      differential reactivity and food neophobia in toddlers, with the hypothesis that
      the more responsive a toddler was across food odours or tastes, the more
      neophobic s/he would be. An additional objective was to determine whether the
      potential relationships between smell (or taste) differential reactivity and food
      neophobia differ according to gender. One hundred and twenty-three toddlers aged
      from 20 to 22 months from the Opaline birth cohort (Observatory of Food
      Preferences in Infants and Children) were involved. A questionnaire was used to
      assess child's food neophobia. Toddlers' differential reactivity for smell (and
      for taste) was defined as the variability of behavioural responses over 8
      odorants, and over the five basic tastes. Smell and taste differential
      reactivities were not correlated. Food neophobia scores were modestly but
      significantly positively correlated with smell differential reactivity but not
      with taste differential reactivity. When gender was considered, smell reactivity
      and neophobia were correlated only among boys. This indicates the need to study
      smell and taste reactivity separately to determine their associations with eating
      behaviours. This suggests that the rejection of novel foods in neophobic boys
      could be partly due to food odour. This finding is new and clearly requires
      further investigation. 

PMID- 26208909
TI  - [In time: how and when should we clamp the umbilical cord: does it really
      matter?].

PMID- 26208910
TI  - Reproduction, aging and mortality rate in social subterranean mole voles
      (Ellobius talpinus Pall.).
AB  - Eusocial subterranean rodents of the Bathyergidae family have enormous longevity.
      The long lifespan of these species is associated with negligible senescence, that
      is, an absence of the signs of age-related deterioration in physical condition.
      The question arises as to whether these features are unique to eusocial
      Bathyergids or typical of other social subterranean rodents as well. In the
      present study, we analysed data from observations of a social subterranean
      Microtinae rodent, the northern mole vole (Ellobius talpinus Pall.), which, like
      mole-rats, has reproductive skew. Among the individuals captured in the wild and
      maintained in captivity, females that reproduced lived significantly longer than
      non-breeding females. We did not find any changes in muscle strength with age in
      any of the demographic groups studied. Faecal glucocorticoid concentrations
      before death were significantly higher in non-breeding females than in breeding
      females and males. Increased adrenocortical activity may be one mechanism
      responsible for the decreased lifespan of non-reproducing individuals of social
      subterranean rodents. We conclude that the patterns of aging, although different
      in some respects, are generally common for social subterranean rodents of
      different taxonomic groups. 

PMID- 26208911
TI  - [From FRANCE 2 to FRANCE TAVI: are indications, technique and results of
      transcatheter aortic valve replacement the same?].
AB  - Transcatheter aortic valve implantation (TAVI) is indicated in patients with
      severe symptomatic aortic stenosis who are not suitable for surgery or should be
      considered when there is a high surgical risk as assessed by a heart team. There
      is a decrease in mean logistic EuroSCORE since January 2010, which translates a
      gradual evolution in patients' selection. Expertise of geriatricians to further
      assess frailty is a key step in the risk stratification process of this elderly
      population (mean age: 83.4+/-7.3 years). Femoral access is used in 80% of cases
      with a procedural success rate higher than 95%. In-hospital mortality rate is
      5.9%. The main complications of the procedure are aortic annulus rupture (0.9% in
      FRANCE TAVI), tamponade (2.3%), stroke (2.2%), severe paravalvular leak (1.3%)
      and permanent pacemaker implantation (15%). The awaited results of PARTNER II and
      SURTAVI may lead to expand the indications to lower-risk patients if it is shown
      that TAVI is non-inferior to surgery in this population which has been suggested
      by the recent randomized NOTION Trial while the CoreValve Pivotal Trial even
      points in the direction of a possible superiority of the percutaneous technique
      over surgery.

PMID- 26208912
TI  - Trauma Ultrasound.
AB  - Ultrasound plays a pivotal role in the evaluation of acute trauma patients
      through the use of multi-site scanning encompassing abdominal, cardiothoracic,
      vascular and skeletal scans. In a high-speed polytrauma setting, because
      exsanguinations are the primary cause of trauma morbidity and mortality,
      ultrasound is used for quick and accurate detection of hemorrhages in the
      pericardial, pleural, and peritoneal cavities during the primary Advanced Trauma
      Life Support (ATLS) survey. Volume status can be assessed non-invasively with
      ultrasound of the inferior vena cava (IVC), which is a useful tool in the initial
      phase and follow-up evaluations. Pneumothorax can also be quickly detected with
      ultrasound. During the secondary survey and in patients sustaining low-speed or
      localized trauma, ultrasound can be used to help detect abdominal organ injuries.
      This is particularly helpful in patients in whom hemoperitoneum is not identified
      on an initial scan because findings of organ injuries will expedite the next
      test, often computed tomography (CT). Moreover, ultrasound can assist in
      detection of fractures easily obscured on radiography, such as rib and sternal
      fractures. 

PMID- 26208913
TI  - Expression of histamine receptors in the human endolymphatic sac: the molecular
      rationale for betahistine use in Menieres disease.
AB  - The human endolymphatic sac (ES) is situated in a duplicature of the dura in the
      posterior cranial fossa and constitutes a part of the inner ear. The sac
      possesses immunological capacities and is responsible for a major part of the
      trans-epithelial ion transport occurring within the inner ear, via molecular
      mechanisms similar to that of the kidney collecting duct epithelia. Dysfunction
      of the trans-epithelial ion transport has been hypothesized as the reason for the
      endolymphatic hydrops occurring in Menieres diseases. Thus, candidate drug
      selection for medical treatment of Menieres disease has been based on a potential
      capability of improving trans-epithelial ion transport. However, recent human
      studies seems to rule out diuretic therapy and The Committee for Medicinal
      Products for Human Use redrew the recommendation for trimetazidine (Vastarel)
      treatment in the management of Meniere disease in 2012. This leaves betahistine
      (Betaserc) as the only drug for potential prevention of the incapacitating
      attacks of dizziness, tinnitus and hearing loss. However, the histamine receptors
      targeted by betahistine have never been demonstrated in the human ES.
      Accordingly, this study aims to investigate the expression of histamine receptors
      of the human ES epithelium and sub-epithelial stroma. Following sampling of human
      endolymphatic sac tissue during translabyrinthine surgery, the expression of
      histamine receptor genes was determined by cDNA microarray analysis. Results were
      subsequently verified by immuno-histochemistry. The combined results of
      microarrays and immuno-histochemistry showed expression of the histamine receptor
      HRH1 in the epithelial lining of the ES, whereas HRH3 was expressed exclusively
      in the sub-epithelial capillary network. Receptors HRH2 and -4 were not
      expressed. The present data provide the first direct evidence of a molecular
      rationale for betahistine treatment in Menieres disease. A potential betahistine
      effect in Menieres disease may primarily be through the H3-receptor antagonism,
      leading to inhibition of vestibular neuro-transmission and central vaso-dilation.
      The H1-receptor localization in the ES epithelium suggests an immuno-regulatory
      effect. 

PMID- 26208915
TI  - The effect of cell passage number on osteogenic and adipogenic characteristics of
      D1 cells.
AB  - Cell line passage number is an important consideration when designing an
      experiment. At higher passages, it is generally understood that cell health
      begins to decline and, when this occurs, the result can be variable data.
      However, there are no specific guidelines regarding optimal passage range, and
      this information is dependent on cell type. To explore these variabilities, low
      passage D1 cells were thawed (passage 3) and passaged serially until a much
      higher number (passage 34). Samples were taken every five passages and analyzed
      for alkaline phosphatase and triglyceride; also, the gene expression of both
      adipogenic and osteogenic markers was tested. The results indicate that the
      growth rate of these cells did slow down after passage 30. However, expression of
      the osteogenic characteristics seemed to cycle, with the highest levels seen at
      passage 4 and 24. The adipocyte expression levels remained the same throughout
      the study. 

PMID- 26208914
TI  - Astrocyte Transcriptome from the Mecp2(308)-Truncated Mouse Model of Rett
      Syndrome.
AB  - Mutations in the gene encoding the transcriptional modulator methyl-CpG binding
      protein 2 (MeCP2) are responsible for the neurodevelopmental disorder Rett
      syndrome which is one of the most frequent sources of intellectual disability in
      women. Recent studies showed that loss of Mecp2 in astrocytes contributes to Rett
      like symptoms and restoration of Mecp2 can rescue some of these defects. The goal
      of this work is to compare gene expression profiles of wild-type and mutant
      astrocytes from Mecp2(308/y) mice (B6.129S-MeCP2<tm1Heto>/J) by using Affymetrix
      mouse 2.0 microarrays. Results were confirmed by quantitative real-time RT-PCR
      and by Western blot analysis. Gene set enrichment analysis utilizing Ingenuity
      Pathways was employed to identify pathways disrupted by Mecp2 deficiency. A total
      of 2152 genes were statistically differentially expressed between wild-type and
      mutated samples, including 1784 coding transcripts. However, only 257 showed fold
      changes >1.2. We confirmed our data by replicative studies in independent primary
      cultures of cortical astrocytes from Mecp2-deficient mice. Interestingly, two
      genes known to encode secreted proteins, chromogranin B and lipocalin-2, showed
      significant dysregulation. These proteins secreted from Mecp2-deficient glia may
      exert negative non-cell autonomous effects on neuronal properties, including
      dendritic morphology. Moreover, transcriptional profiling revealed altered Nr2f2
      expression which may explain down- and upregulation of several target genes in
      astrocytes such as Ccl2, Lcn2 and Chgb. Unraveling Nr2f2 involvement in Mecp2
      deficient astrocytes could pave the way for a better understanding of Rett
      syndrome pathophysiology and offers new therapeutic perspectives.

PMID- 26208916
TI  - MutAIT: an online genetic toxicology data portal and analysis tools.
AB  - Assessment of genetic toxicity and/or carcinogenic activity is an essential
      element of chemical screening programs employed to protect human health. Dose
      response and gene mutation data are frequently analysed by industry, academia and
      governmental agencies for regulatory evaluations and decision making. Over the
      years, a number of efforts at different institutions have led to the creation and
      curation of databases to house genetic toxicology data, largely, with the aim of
      providing public access to facilitate research and regulatory assessments. This
      article provides a brief introduction to a new genetic toxicology portal called
      Mutation Analysis Informatics Tools (MutAIT) (www.mutait.org) that provides easy
      access to two of the largest genetic toxicology databases, the Mammalian Gene
      Mutation Database (MGMD) and TransgenicDB. TransgenicDB is a comprehensive
      collection of transgenic rodent mutation data initially compiled and collated by
      Health Canada. The updated MGMD contains approximately 50 000 individual mutation
      spectral records from the published literature. The portal not only gives access
      to an enormous quantity of genetic toxicology data, but also provides statistical
      tools for dose-response analysis and calculation of benchmark dose. Two important
      R packages for dose-response analysis are provided as web-distributed
      applications with user-friendly graphical interfaces. The 'drsmooth' package
      performs dose-response shape analysis and determines various points of departure
      (PoD) metrics and the 'PROAST' package provides algorithms for dose-response
      modelling. The MutAIT statistical tools, which are currently being enhanced,
      provide users with an efficient and comprehensive platform to conduct
      quantitative dose-response analyses and determine PoD values that can then be
      used to calculate human exposure limits or margins of exposure.

PMID- 26208917
TI  - Electrical carotid sinus stimulation: chances and challenges in the management of
      treatment resistant arterial hypertension.
AB  - Treatment resistant arterial hypertension is associated with excess
      cardiovascular morbidity and mortality. Electrical carotid sinus stimulators
      engaging baroreflex afferent activity have been developed for such patients.
      Indeed, baroreflex mechanisms contribute to long-term blood pressure control by
      governing efferent sympathetic and parasympathetic activity. The first-generation
      carotid sinus stimulator applying bilateral bipolar stimulation reduced blood
      pressure in a controlled clinical trial but nevertheless failed to meet the
      primary efficacy endpoint. The second-generation device utilizes smaller
      unilateral unipolar electrodes, thus decreasing invasiveness of the implantation
      while saving battery. An uncontrolled clinical study suggested improvement in
      blood pressure with the second-generation device. We hope that these findings as
      well as preliminary observations suggesting cardiovascular and renal organ
      protection with electrical carotid sinus stimulation will be confirmed in
      properly controlled clinical trials. Meanwhile, we should find ways to better
      identify patients who are most likely to benefit from electrical carotid sinus
      stimulation. 

PMID- 26208918
TI  - Economic impact of HIV/AIDS: a systematic review in five European countries.
AB  - The HIV/AIDS disease represent a priority for all health authorities in all
      countries and it also represents serious added socioeconomic problems for
      societies over the world. The aim of this paper is to analize the economic impact
      associated to the HIV/AIDS in an European context. We conducted a systematic
      literature review for five different countries (France, Germany, Italy, Spain and
      United Kingdom) and searched five databases. Three types of analyses were
      undertaken: descriptive statistics; quantitative analysis to calculate mean
      costs; and comparison across countries. 26 papers were included in this study
      containing seventy-six cost estimates. Most of the studies analyzed the health
      care cost of treatment of HIV/AIDS. Only 50% of the cost estimates provided mean
      lymphocyte count describing the patients' disease stage. Approximately thirty
      percent of cost estimates did not indicate the developmental stage of the illness
      in the patients included. There is a high degree of variability in the estimated
      annual cost per patient of the treatments across countries. There is also a great
      disparity in total healh care costs for patients with lymphocyte counts between
      200CD4+/mm3 and 500 CD4/mm3, although the reason of variation is unclear. In
      spite of the potential economic impact in terms of productivity losses and cost
      of formal and informal care, few studies have set out to estimate the non-medical
      costs of HIV/AIDS in the countries selected. Another important result is that,
      despite the low HIV/AIDS prevalence, its economic burden is very relevant in
      terms of the total health care costs in this five countries. This study also
      shows that there are relatively few studies of HIV costs in European countries
      compared to other diseases. Finally, we conclude that the methodology used in
      many of the studies carried out leaves ample room for improvement and that there
      is a need for these studies to reflect the economic impact of HIV/AIDS beyond
      health care including other components of social burden. 

PMID- 26208919
TI  - Reservation wage of female volunteer community health workers in Dhaka urban
      slums: a bidding game approach.
AB  - BACKGROUND: BRAC, a large Bangladeshi NGO, recently has been using female
      volunteer community health workers (CHWs) in Dhaka urban slums to provide
      maternal and child health services. Due to erratic performance-based income and
      higher opportunity cost the urban CHWs lose motivation which contributes to high
      dropout and poor performance. This results challenges for the cost effectiveness
      and sustainability of the urban health program. CHWs also consider their
      performance-based income very low compare to their work load. So, CHWs raise
      their voice for a fixed income. In order to understand this problem we explored
      fixed income for CHWs and the correlates that influence it. We surveyed a sample
      of 542 current CHWs. We used bidding game approach to derive the equilibrium
      reservation wage for CHWs for providing full-time services. Then, we performed
      ordered logit models with bootstrap simulation to identify the determinants of
      reservation wage. RESULTS: The average reservation wage of CHWs to continue their
      work as full-time CHWs rather than volunteer CHWs was US$24.11 which was three
      times higher than their current performance-based average income of US$ 8.03.
      Those CHWs received additional health training outside BRAC were 72% and those
      who joined with an expectation of income were 62% more likely to ask for higher
      reservation wage. On the contrary, CHWs who were burdened with household loan
      were 65% and CHWs who had alternative income generating scope were 47% less
      likely to ask for higher reservation wage. Other important factors we identified
      were BRAC village organization membership, competition with other health services
      providers, performance as a CHW, and current and past monthly CHW income.
      CONCLUSIONS: The findings of this study are relevant to certain developing
      countries such as Bangladesh and Tanzania which commonly use volunteer CHWs, and
      where poor retention and performance is a common issue due to erratic and
      performance-based income. So, the study has implications in improving retention
      of health workers as well as their level of performance. The study also suggests
      that the financial incentives provided to CHWs should be clearly based on their
      qualifications and opportunity cost to ensure a high performing and motivated
      health workforce.

PMID- 26208920
TI  - Long-term cost effectiveness of ticagrelor in patients with acute coronary
      syndromes in Thailand.
AB  - OBJECTIVES: To evaluate the long-term cost-effectiveness of ticagrelor and ASA
      versus generic and branded clopidogrel and ASA in patients with ACS based on a
      Thai cost database. METHODS: A one-year decision tree and a long-term Markov
      model were constructed to estimate lifetime costs and quality-adjusted life years
      (QALYs). For the first year, data from PLATO (NCT00391872) were used to estimate
      the rate of cardiovascular events, resource use, and QALYs. For year 2 onwards,
      clinical effectiveness was estimated conditional on individual health states that
      occurred during the first year. RESULTS: In the base-case analysis, the
      incremental cost-effectiveness ratio (ICER) with ticagrelor was 292,504 ($9,476)
      and 60,055 ($1,946) THB($)/QALY compared with generic and branded clopidogrel,
      respectively. The probability of ticagrelor being cost-effective was above 99% at
      a threshold of 160,000 THB/QALY compared with branded clopidogrel. CONCLUSIONS:
      This health economic analysis provides cost effectiveness data for ticagrelor
      compared with both generic and branded clopidogrel in Thailand. Based on this
      analysis, it appears that ticagrelor is an economically valuable treatment for
      ACS compared with branded clopidogrel within the Thai context.

PMID- 26208922
TI  - Effect of health insurance coverage on labor allocation: evidence from US farm
      households.
AB  - In the past three decades, farm families have relied on government payments and
      off-farm income to reduce income risk and increase total household income. Many
      studies have analyzed the role of government payments; however, little is known
      about the impact of health insurance coverage on labor allocation. This study
      builds on previous literature by using copulas to test for dependence in the
      labor allocation, addressing the importance of fringe benefits to the farm
      household, and determining how these considerations affect our knowledge of the
      impact of fringe benefits on off-farm labor. The results indicate that the off
      farm hours worked by the operator and spouse are jointly determined; health
      insurance coverage is an endogenous variable. Using the predicted probability of
      insurance coverage and joint estimation techniques, we find a positive and highly
      significant relationship with the hours worked off-farm. Further, we find that
      both coupled and decoupled payments are negatively correlated with the hours
      worked off-farm. 

PMID- 26208921
TI  - Modeling rheumatoid arthritis using different techniques - a review of model
      construction and results.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory disease with
      severe effects on the functional ability of patients. Due to the prevalence of
      0.5 to 1.0 percent in western countries, new treatment options are a major
      concern for decision makers with regard to their budget impact. In this context,
      cost-effectiveness analyses are a helpful tool to evaluate new treatment options
      for reimbursement schemes. OBJECTIVES: To analyze and compare decision analytic
      modeling techniques and to explore their use in RA with regard to their
      advantages and shortcomings. METHODS: A systematic literature review was
      conducted in PubMED and 58 studies reporting health economics decision models
      were analyzed with regard to the modeling technique used. RESULTS: From the 58
      reviewed publications, we found 13 reporting decision tree-analysis, 25 (cohort)
      Markov models, 13 publications on individual sampling methods (ISM) and seven
      discrete event simulations (DES). Thereby 26 studies were identified as
      presenting independently developed models and 32 models as adoptions. The
      modeling techniques used were found to differ in their complexity and in the
      number of treatment options compared. Methodological features are presented in
      the article and a comprehensive overview of the cost-effectiveness estimates is
      given in Additional files 1 and 2. DISCUSSION: When compared to the other
      modeling techniques, ISM and DES have advantages in the coverage of patient
      heterogeneity and, additionally, DES is capable to model more complex treatment
      sequences and competing risks in RA-patients. Nevertheless, the availability of
      sufficient data is necessary to avoid assumptions in ISM and DES exercises,
      thereby enabling biased results. Due to the different settings, time frames and
      interventions in the reviewed publications, no direct comparison of modeling
      techniques was applicable. The results from other indications suggest that
      incremental cost-effective ratios (ICERs) do not differ significantly between
      Markov and DES models, but DES is able to report more outcome parameters.
      CONCLUSIONS: Given a sufficient data supply, DES is the modeling technique of
      choice when modeling cost-effectiveness in RA. Otherwise transparency on the data
      inputs is crucial for valid results and to inform decision makers about possible
      biases. With regard to ICERs, Markov models might provide similar estimates as
      more advanced modeling techniques.

PMID- 26208923
TI  - Parents' willingness to pay for the prevention of childhood overweight and
      obesity.
AB  - OBJECTIVE: To determine parental willingness-to-pay (WTP) for childhood obesity
      prevention. METHODS: Cross-sectional data from the follow-up measurements (2011)
      of a health promotion programme in German primary schools. Data collection
      included anthropometric measurements of children and self-administered
      questionnaires for parents, including WTP assessment. Mann-Whitney U-Test was
      used for differences between groups, and regression analysis to identify factors
      associated with general WTP and amount of WTP. RESULTS: From 1 534 parents, 97.8%
      considered overweight/obesity to be serious public health problems. A general WTP
      to reduce the incidence of childhood overweight/obesity by half, was declared by
      48.8%. Parents of overweight/obese children showed with 61.4%, significantly more
      frequently, their general WTP than the others with 47.2% (p = 0.001). Mean WTP
      was <euro>23.04 (99% confidence interval (CI) [22.45; 23.75]) per month. Parents
      of centrally obese children showed significantly higher WTP than parents of the
      other children (p = 0.001). General WTP and the amount of WTP were associated
      with the central obesity of the child, migration status and household income.
      Additionally, general WTP was associated with maternal obesity. CONCLUSIONS:
      Nearly half of the parents were willing to invest in prevention of obesity. The
      general WTP significantly occurs more often and with higher amount in affected
      parents.

PMID- 26208924
TI  - Pharmaceutical regulation in Europe and its impact on corporate R&D.
AB  - OBJECTIVES: Many European countries regulate the markets for prescription drugs
      in order to cope with rising health expenditures. On the other hand, regulation
      distorts incentives to invest in pharmaceutical R&D. This study aims at
      empirically assessing the impact of regulation on pharmaceutical R&D
      expenditures. METHODS: We analyze a sample of 20 leading pharmaceutical companies
      between 2000 and 2008. The share of sales in Europe serves as a proxy for the
      degree of pharmaceutical regulation. We control for other firm specific
      determinants of R&D such as cash flow, company size, leverage ratio, growth rate,
      and Tobin's q. RESULTS: Our results suggest a nonlinear relationship between
      European sales ratio and R&D intensity. Beyond a threshold of 33% of sales
      generated in Europe, a higher presence in Europe is associated with lower R&D
      investments. CONCLUSION: The results can be interpreted as further evidence of
      the deteriorating effect of regulation on firm's incentives to invest in R&D.

PMID- 26208925
TI  - Costing of diabetes mellitus type II in Cambodia.
AB  - BACKGROUND: Diabetes Mellitus Type II (T2DM) is a major and growing medical,
      social and economic burden in the East-Asian country of Cambodia. However, no
      economic modelling has been done to predict the number of cases and the budget
      impact. OBJECTIVE: This paper forecasts the epidemiological and economic
      consequences of T2DM in Cambodia. The Ministry of Health and related donor
      agencies are supported to select the most cost-effective interventions against
      the disease. At the same time this paper demonstrates the relevance and potential
      of health economic modelling for least developed countries. METHODS: We developed
      a Markov-Model for the specific situation of Cambodia. Data was taken from the
      scientific literature, grey literature in Cambodia and key-informant interviews.
      RESULTS: The number of people living with T2DM is steadily increasing from
      145,000 in the year 2008 to 264,000 in the year 2028 (+82 %). In the year 2008
      the diagnosed T2DM patients would incur costs of some 2 million US$ to cover all
      of diabetes treatment. 57 % of this amount would have to be spent for OAD
      therapy, the rest for insulin therapy. In the year 2028 this amount will have
      grown to some 4 million US$. If all patients (incl. non-diagnosed) had to be paid
      for the respective figure would be 5.5 million and 11 million US$. Screening for
      T2DM is only cost-effective if the sensitivity of the test is high while the unit
      price is low. The results of this simulation call for targeting the high-risk
      groups. However, an increased availability of Oral Anti-Diabetic and Insulin
      Therapy is highly cost-effective. DISCUSSION: Type 2 Diabetes Mellitus is a major
      public health challenge in Cambodia. The simulations clearly indicate that
      prevention and treatment of this disease is highly cost-effective. However, not
      everything that is cost-effective might be affordable in Cambodia. This country
      will require external support to ease the growing burden of T2DM.

PMID- 26208926
TI  - Evaluating the administration costs of biologic drugs: development of a cost
      algorithm.
AB  - Biologic drugs, as with all other medical technologies, are subject to a number
      of regulatory, marketing, reimbursement (financing) and other demand-restricting
      hurdles applied by healthcare payers. One example is the routine use of cost
      effectiveness analyses or health technology assessments to determine which
      medical technologies offer value-for-money. The manner in which these assessments
      are conducted suggests that, holding all else equal, the economic value of
      biologic drugs may be determined by how much is spent on administering these
      drugs or trade-offs between drug acquisition and administration costs. Yet, on
      the supply-side, it seems very little attention is given to how manufacturing and
      formulation choices affect healthcare delivery costs. This paper evaluates
      variations in the administration costs of biologic drugs, taking care to ensure
      consistent inclusion of all relevant cost resources. From this, it develops a
      regression-based algorithm with which manufacturers could possibly predict,
      during process development, how their manufacturing and formulation choices may
      impact on the healthcare delivery costs of their products. 

PMID- 26208927
TI  - Early health economic evaluation of the future potential of next generation
      artificial vision systems for treating blindness in Germany.
AB  - The next generation of artificial vision devices (AVDs), which is currently
      developed in pre-clinical settings, has the potential to improve the vision of
      blind patients with retinitis pigmentosa (RP) in a manner that they will be
      categorized as visual impaired but no more as blind. This unprecedented vision
      improvement will result in a mentionable quality of life gain which poses the
      question at which costs the next generation AVDs are to be regarded as cost
      effective, from a German healthcare payer perspective. In order to answer this
      research question a Markov model was developed to simulate and to compare the
      costs and effects of next generation AVDs versus best supportive care (BSC).
      Applying the base case settings resulted in incremental costs of <euro>107,925,
      in 2.03 incremental quality-adjusted life years (QALYs) and in a cost
      effectiveness ratio of <euro>53,165 per QALY gained. Probabilistic and
      deterministic sensitivity analyses as well as scenario analyses for the effect
      size and the AVD costs were performed in order to investigate the robustness of
      results. In these scenario analyses a strong variation of the cost-effectiveness
      results was obtained ranging from <euro>23,512 (best case) to <euro>176,958
      (worst case) per QALY gained by AVD therapy. This early health economic
      evaluation has to handle with three main uncertainty factors: the effect size of
      next generation AVDs, the costs of next generation AVDs and the WTP threshold
      that might be applied in RP patients, which reflect the main limitations of the
      presented assessment. In conclusion the presented early cost-effectiveness
      evaluation has obtained that next generation AVDs have the potential to be a cost
      effective therapy option in patients with RP in Germany. The innovative nature,
      the high unmet medical need and the expected unprecedented efficacy of next
      generation AVDs will highly likely lead to the case that even relatively high
      incremental cost-effectiveness ratios, that have been obtained when simulating
      various effect and pricing scenarios, will be regarded as acceptable from a
      German healthcare payer perspective. 

PMID- 26208928
TI  - Defining hospital markets - an application to the German hospital sector.
AB  - The correct definition of the product market and of the geographic market is a
      prerequisite for assessing market structures in antitrust cases. For hospital
      markets, both dimensions are controversially discussed in the literature. Using
      data for the German hospital market we aim at elaborating the need for
      differentiating the product market and at investigating the effects of different
      thresholds for the delineation of the geographic market based on patient flows.
      Thereby we contribute to the scarce empirical evidence on the structure of the
      German hospital market. We find that the German hospital sector is highly
      concentrated, confirming the results of a singular prior study. Furthermore,
      using a very general product market definition such as "acute in-patient care"
      averages out severe discrepancies that become visible when concentration is
      considered on the level of individual diagnoses. In contrast, varying thresholds
      for the definition of the geographic market has only impact on the level of
      concentration, while the correlation remains high. Our results underline the need
      for more empirical research concerning the definition of the product market for
      hospital services. 

PMID- 26208929
TI  - Results from an exploratory study to test the performance of EQ-5D-3L valuation
      subsets based on orthogonal designs, and an investigation into some modeling and
      transformation alternatives for the utility function.
AB  - BACKGROUND: EQ-5D-3L valuation studies continue to employ the MVH protocol or
      variants of MVH. One issue that has received attention is the selection of the
      states for direct valuation by respondents. Changes in the valuation subset have
      been found to change the coefficients of the utility function. The purpose of
      this study was to test the performance of valuation subsets based on orthogonal
      experiment designs. The design of the study also allowed a comparison of models
      based on raw or untransformed VAS values with values transformed at the level of
      the respondent and at the aggregate level. METHODS: Two different valuation
      subsets were developed based on orthogonal arrays. A VAS elicitation was
      undertaken with two groups of similar respondents and the resulting utility
      functions based on the valuations of the two different valuation subsets were
      compared using mean absolute errors between model and observed values, and by
      correlation with values in and out of sample. The impact of using untransformed
      versus VAS values transformed at the level of the individual and at aggregate
      level and the inclusion of a constant term in the utility functions were also
      investigated. RESULTS: The utility functions obtained from the two valuation
      subsets were very similar. The models that included a constant and based on raw
      VAS values from the two valuation studies returned rank correlation coefficients
      of 0.994 and 0.995 when compared with respective observed values. MAEs of model
      values with observed values were 2.4% or lower for all models that included a
      constant term. Several models were developed and evaluated for the combined data
      (from both valuation subsets). The model that included the N3 term performed
      best. CONCLUSIONS: The finding that two very different valuation subsets can
      produce strikingly similar utility functions suggests that orthogonal designs
      should be given some attention in further studies. The impact of rescaling VAS
      values at the level of the individual versus at aggregate level had minimal
      impact on the performance of the models when compared to models based on the raw
      VAS values.

PMID- 26208930
TI  - Commercial plasma donation and individual health in impoverished rural China.
AB  - BACKGROUND: Blood collection following nonstandard operations largely increases
      the risks of infectious diseases through cross-contamination. Commercial plasma
      donation and the resulting HIV/AIDS and hepatitis C epidemics in central China in
      the 1990s killed more than one million people. Many blood banks have since moved
      to more remote southwest provinces, which have become new suppliers of blood
      plasma. METHODS: Utilizing a primary longitudinal survey, this paper documents
      commercial plasma donation and estimates its negative health impacts in
      impoverished rural China using individual fixed effect models. Both the linear
      regression model and generalized linear models are utilized. RESULTS: Attracted
      by the financial compensation, a majority of plasma donors are poor, and bear
      grave consequences of malnutrition and worse health status as a result of
      unhygienic and frequent donations. Donating plasma is associated with a .83
      standard deviation (SD) decline in self-rated health, a .54 SD lower self-rated
      health relative to peers in their age group, a .74 SD higher chance of being
      infected with hepatitis, lacking of strength to conduct farm work, and
      experiencing appetite loss, fatigue, nausea, and vomiting. DISCUSSION: Results
      indicate an urgent need of more comprehensive and effective interventions on
      hepatitis screening, diagnosis, and treatment among plasma donors in less
      developed contexts to eliminate cross-infection of infectious diseases and
      possible widespread epidemic in the future. Besides, we should encourage
      voluntary plasma donation to gradually crowd out paid donation.

PMID- 26208931
TI  - Relevance of indirect comparisons in the German early benefit assessment and in
      comparison to HTA processes in England, France and Scotland.
AB  - Early benefit assessment in Germany under the legislative framework of AMNOG
      (Arzneimittelmarktneuordnungsgesetz) requires direct comparisons of the new drug
      with appropriate comparators determined by the Federal Joint Committee (G-BA). In
      case no head-to-head studies are available for direct comparisons, the submission
      of indirect comparisons is permitted to assess the additional benefit of the new
      drug. However, the Institute for Quality and Efficiency in Health Care (IQWiG)
      states a clear preference for head-to-head trials and defines strict requirements
      for indirect comparisons to be considered in the benefit assessment. Similar
      requirements also exist in other countries with mandatory health technology
      assessments (HTA), like France, England and Scotland. Our evaluation shows that a
      comparison of the different HTA regarding indirect comparisons is difficult.
      Overall, external preconditions and methodological requirements are demanding and
      hardly to fulfill by pharmaceutical companies for implementation of indirect
      comparisons in early benefit assessment. The determination of the appropriate
      comparators, outcomes, patient subgroups and study choice are the main target
      within indirect comparisons for the future. To compare and assess submitted
      indirect comparisons it would be desirable that a transparent process was
      established, including the mandatory publication of HTA-reports within Europe and
      international guidelines, accepted by a large number of HTA-agencies. 

PMID- 26208932
TI  - Biologic TNF inhibiting agents for treatment of rheumatoid arthritis: persistence
      and dosing patterns in Germany.
AB  - OBJECTIVE: To obtain detailed real-world data on persistence and dosing patterns
      in the utilisation of the TNF inhibitors adalimumab, etanercept, and infliximab
      in rheumatoid arthritis (RA) patients treated in Germany. METHODS: In this
      retrospective observational study claims data of a major German health insurance
      fund between 2005 and 2008 were analysed. Patients receiving at least one
      prescription of adalimumab, etanercept or infliximab were identified and
      categorised as "TNF inhibitor naive" or "TNF inhibitor continuing". For the
      calculation of TNF inhibitor persistence a survival analysis with the Kaplan
      Meier estimator was used. A Cox regression was used to analyse, if any relevant
      factors were influencing persistence. Dosage increase rates were analysed for
      adalimumab, etanercept and infliximab. Sensitivity analyses based on variations
      in gap length were conducted. RESULTS: A total of 2,201 RA patients were
      identified. 1,468 of these patients were TNF inhibitor naive patients and 733
      were defined as TNF inhibitor continuing patients. There were no significant
      differences in the treatment persistence rates between adalimumab, etanercept and
      infliximab for TNF inhibitor naive and continuing patients. The persistence rate
      after three years was 22.47% for adalimumab, 24.27% for etanercept and 21.49% for
      infliximab naive patients. For continuing patients, the persistence rate after
      three years was 32.88% for adalimumab, 30.95% for etanercept, and 33.90% for
      infliximab, respectively. Gender, medication and Charlson Comorbidities Index did
      not influence the persistence significantly. Dosage increase occurred in 7.3%
      adalimumab, 1.4% etanercept, and 17.2% infliximab naive patients and 5.8%, 1.1%
      and 11.9% respectively in the continuing patients. CONCLUSIONS: In this study,
      there were no significant differences in persistence among adalimumab, etanercept
      and infliximab treated patients. Consistent with previous research, there was a
      higher dose escalation for infliximab than for the two subcutaneous treatments,
      adalimumab or etanercept.

PMID- 26208933
TI  - A multilevel analysis of prenatal care and birth weight in Kenya.
AB  - The paper investigates the effect of adequate use of prenatal care on birth
      weight in Kenya using data from the Kenya Demographic and Health Survey of 2008
      2009 together with additional administrative data. Both a single-level model and
      a multi-level model are estimated. The estimation strategy controls for potential
      sample selection bias, potential endogeneity of prenatal care, and potential
      unobserved heterogeneity. The results indicate that adequate use of prenatal care
      increases birth weight, holding other factors constant. We further observe that
      the single-level model overstates the effect of prenatal care on birth weight.
      The results imply that infant health can be improved by using prenatal care
      adequately. The study calls for the pursuit of policies that encourage adequate
      use of prenatal care by expectant mothers such as ensuring availability of
      skilled health care providers such as doctors and nurses at prenatal care
      clinics, reducing the average distances mothers have to cover when seeking
      prenatal care services, intensifying education of females as a way of empowering
      them to be able to make the right choices regarding when to seek prenatal care
      and from whom, and increasing income opportunities for households. 

PMID- 26208934
TI  - Willingness to pay for informal care in France: the value of funding support
      interventions for caregivers.
AB  - OBJECTIVES: This article aims to assess the relationship between the monetary
      value of informal care - approximated with the caregiver's willingness to pay to
      reduce caregiving time - and the caregiver's need of three types of support
      services: care training, respite care and support group. Developing such services
      may be the only way to provide sustainable informal care in the future, along
      with efficient allocation. DATA & METHODS: Data used stemmed from two
      representative national surveys conducted by French National Institute of
      Statistics and Economic Studies and the French Head Office of Research, Studies,
      Evaluation and Statistics of the Social Affairs Ministry in 2008. The contingent
      valuation method was used to approximate the monetary value of informal care. The
      model was run on 223 informal caregivers of people with Alzheimer's Disease.
      Statistical analyses were performed using Heckman's two-step estimation strategy,
      which is known to correct selection bias. RESULTS: On average, one hour of
      informal care was estimated at <euro>12.1. Monetary value of informal care was
      influenced by the caregiver's need of care training (p<0.01). No similar
      association was found for respite care or support group. DISCUSSION: Since
      informal caring value increases with caregivers' need of care training, improving
      caring skills and capabilities through training support is likely to improve its
      benefits.

PMID- 26208935
TI  - The possibilities of day surgery system development within the health policy in
      Slovakia.
AB  - BACKGROUND: In the day surgery system are intertwined elements of state health
      policy, health care payers' interests, employers of health care system, as well
      as the interests and wishes of patients. A problem in the health policy is to
      find a way to regulate ambulatory and short-term surgical procedures, which are
      hardly distinguishable, and still fulfil the requirements of transparent
      financing, quality and security. The objective of this paper is to highlight the
      reasons for the long-term stagnation in Slovakia day surgery and the
      possibilities of eliminating the structural drivers causing this negative
      phenomenon. METHODS: Due to the nature of the analyzed data and desired outcomes,
      we selected application of correspondence analysis. Results of correspondence
      analysis provide valuable information necessary for the projection of
      specialization of one day surgery clinics for that type of procedure, as well as
      for the support of the new clinics creation (also with the potential state
      support), the pricing policy, systemic reduction of beds what is connected with
      reduction of underutilized departments in hospitals, in order to optimize
      management processes in the healthcare system. RESULTS: Contribution reveals
      negative aspects which causing a low level of day surgery in Slovakia. Moreover,
      it reveals the approaches of the different subjects of day surgery. Presented
      options for setting optimal strategy supporting its development are based on the
      results of the analysis. Correspondence analysis provided valuable information of
      present structure of the day surgery system. The determined similarity of the
      regions and association of specialized fields indicate specific settings of the
      day surgery system and its components that are inevitable to analyze in the
      subsequent analytical process. CONCLUSIONS: Results of the analysis are very
      important in order to set up the system measures in the process of its further
      development, which should be part of the strategic plan of each health system. On
      conceptual and methodological issues related with reporting of day surgery
      performances are highlighting international organizations such as the OECD,WHO.
      JEL CLASSIFICATION: I13, I18, H51.

PMID- 26208936
TI  - Forgone care and financial burden due to out-of-pocket payments within the German
      health care system.
AB  - BACKGROUND: The amount of out-of-pocket (OOP) payments within the German health
      care system has risen steadily within the last years. OOP payments aim to
      strengthen patients' cost awareness and try to restrict the demand on medical
      necessary treatments. However, besides the intended decline of non-induced health
      care services there's a risk that people also forgo necessary treatments because
      the utilization of health care services depends not only on need-factors but also
      on the ability to pay for it. Therefore, this paper aims to analyze the
      determinants of the total amount of OOP payments, the financial burden caused by
      OOP payments and the relinquishment of health care services due to OOP payments.
      DATA AND METHODS: The empirical analysis is based on cross-sectional data of the
      German subsample (n = 2851) of the Survey of Health, Ageing and Retirement in
      Europe (SHARE). SHARE is a representative panel study among private households
      with persons above the age of 50 years and covers a wide range of topics, e.g.
      health behavior, health status and information about the socio-economic status.
      The analysis of the independent variables "total amount of OOP payments",
      "financial burden due to OOP payments" and "forgone care" is carried out by the
      means of descriptive as well as multivariate regression methods. RESULTS:
      Individuals with low income as well as people suffering from chronic illnesses
      face a higher financial burden and forgo health care services more frequently at
      the same time. E.g. the financial burden of people who belong to the lowest
      income quintile is about eight times higher compared to individuals who belong to
      the highest quintile. The probability of forgone care for this group is about 5.6
      percentage points higher [95% CI: 5.2 - 6.0]. CONCLUSION: Especially for the
      group of people with chronic illnesses and low-income earners it cannot be ruled
      out that they also forgo necessary medical treatments due to the relatively high
      financial burden they face. Hence, it is required to facilitate the access to
      necessary care for these groups.

PMID- 26208937
TI  - Expert's comment concerning Grand Rounds case entitled "Surgical challenges in
      the management of cervical kyphotic deformity in patients with severe
      osteoporosis: an illustrative case of a patient with Hajdu-Cheney syndrome" (T.
      A. Mattei, A. A. Rehman, A. Issawi, D. R. Fassett).

PMID- 26208938
TI  - Patient-reported outcome measures unbiased by loss of follow-up. Single-center
      study based on DaneSpine, the Danish spine surgery registry.
AB  - PURPOSE: The purpose of this study is to determine if there are any demographic
      and reporting differences between patients who respond and those who refuse to
      respond to postal questionnaires from the Danish national spine database,
      DaneSpine. METHODS: DaneSpine collects patient-reported data, completed before
      surgery and at 3 months, and at 1, 2, 5, and 10 years postoperatively. The
      database was launched at the Center for Spine Surgery and Research at Lillebaelt
      Hospital on June 1st, 2010. We performed a 1-year follow-up on non-responders
      during a 6-month period between the 1st of August 2013 until the 31st of January
      2014 using a structured phone interview to collect patient-reported outcomes,
      some health information and reasons for non-response. RESULTS: Of the 506
      patients who were 1-year post-operative, three did not have baseline data and six
      had died before the 1-year follow-up. Twenty-four patients had a second spine
      surgery and were re-enrolled in the database. These cases had not reached the 1
      year follow-up period for the second spine surgery and were excluded from the
      analysis. Thus, 473 patients had reached 1-year follow-up. Of these, 57 (12 %)
      did not respond to postal questionnaires. A structured phone interview was
      performed on these 57 non-responders. Non-responders were in general, a decade
      younger than responders, a greater proportion were males and smokers. Apart from
      EQ-5D, there was no difference in patient satisfaction, improvement in back pain
      or leg pain between the responders and non-responders. CONCLUSIONS: Missing data
      from 12 % of patients do not seem to bias conclusions that can be drawn from the
      DaneSpine database at the Center for Spine Surgery and Research at Lillebaelt
      Hospital.

PMID- 26208940
TI  - Index: EUROSPINE 2015 Copenhagen, Denmark, September 2-4.

PMID- 26208939
TI  - Feasibility and trajectory study of anterior transarticular crossing screw
      placement for atlantoaxial joint instability: a cadaveric study and description
      of a novel technique.
AB  - PURPOSE: In unique clinical situations where C1-C2 anterior transarticular screw
      (ATS) fixation is not available or has failed, an anterior transarticular
      crossing screw (ATCS) with transcorporal pathway of the screws inside the
      contralateral promontory of C2 may enhance the stabilization and achieve
      atlantoaxial arthrodesis. The present study was to describe a novel technique of
      ATCS fixation for atlantoaxial joint instability and its applied anatomy, and
      compared it with ATS fixation method. METHODS: Direct measurements using digital
      calipers and a goniometer were conducted on 30 pairs of dried human C1 and C2
      vertebrae. The ATS and ATCS with screws (Phi 4.0 mm) were performed on 11 fresh
      cervical spine specimens. The screw lengths in the C1 and C2, and screw entry
      angles of the ATS and ATCS were measured, respectively. Cadaver specimens were
      dissected to observe the incidence of violation to the important structures
      surrounding the ATS and ATCS fixation technique. RESULTS: There was enough
      osseous space for ATCS placement. The lateral and incline angle of the ATCS was
      36.2 degrees  and 28.7 degrees , respectively. Screw purchase in C2 of the ATCS
      (25.6 mm) was greater than that of the ATS (11.4 mm). The ATCS C1 purchase (14.8
      mm) was similar to the ATS C1 purchase (14.9 mm). No violation to the vertebral
      artery groove, the spinal canal or the atlanto-occipital joint was observed after
      the ATCS placement. CONCLUSION: Anterior transarticular crossing screw is a
      feasible and viable option for atlantoaxial fixation in selected cases. This
      technique achieved remarkable longer screw purchase and could enhance the
      atlantoaxial stability.

PMID- 26208941
TI  - Normal values of cervical spinal cord diffusion tensor in young and middle-aged
      healthy Chinese.
AB  - PURPOSE: Lack of normal reference value of diffusion tensor imaging parameters
      hinders its application in clinical practice. In this study, we aim to establish
      a comprehensive normal DTI database of Chinese subjects. METHODS: Sixty-five
      healthy subjects aged 21-61 years were recruited and underwent 3T DTI scan of
      cervical spine. DTI parameters were measured in whole cord, ventral, lateral and
      dorsal column from C2 to C7 segments. Regions, segments, gender and age-related
      changes of DTI parameters were analyzed. RESULTS: No significant difference was
      found between genders (p > 0.05). DTI parameters significantly differed among
      different cord levels (p < 0.05). FA value in whole cord, grey matter, dorsal and
      ventral column showed significant but weak correlation with age (p < 0.05).
      CONCLUSION: A comprehensive normal database of DTI parameters of cervical spinal
      cord was established. The effect of gender and age-related changes is negligible
      in DTI analysis of cervical spinal cord disorders.

PMID- 26208942
TI  - The association between a lifetime history of work-related low back injury and
      future low back pain: a population-based cohort study.
AB  - PURPOSE: This population-based cohort study investigated the association between
      a lifetime history of a work-related low back injury, in those who had recovered
      to have no or mild low back pain, and the development of troublesome low back
      pain (LBP). A secondary analysis explored the possible effects of
      misclassification of the exposure by examining the association between a lifetime
      history of having taken time off work or performed light duties at work because
      of a work-related low back injury. Current evidence from cross-sectional studies
      suggests that individuals with a history of a work-related low back injury are
      more likely to experience future LBP. However, there is a need to examine this
      association prospectively in a large population-based cohort with adequate
      control of known confounders. METHODS: We formed a cohort of 810 randomly sampled
      Saskatchewan adults with no or mild LBP in September 1995. At baseline,
      participants were asked if they had ever injured their low back at work. The
      secondary analysis asked if they had ever had to take time off work or perform
      light duties at work because of a work-related low back injury. Prospective
      follow-up 6 and 12 months later, asked about the presence of troublesome LBP
      (grade II-IV) on the Chronic Pain Grade Questionnaire. Multivariable Cox
      proportional hazards regression analysis was used to estimate these associations
      while controlling for known confounders. RESULTS: The proportion followed up at 6
      and 12 months was 76 and 65%, respectively. We found an association between a
      history of work-related low back injury and the onset of troublesome LBP after
      controlling for gender (adjusted HRR = 2.24; 95% CI 1.41-3.56). When covariates
      that may also be mediators of the association were added to the model, the effect
      estimate was attenuated (adjusted HRR = 1.37; 95% CI 1.41-3.56). We found a
      similar association between a lifetime history of having taken time off work or
      had to work light duties at work because of a work-related low back injury,
      adjusted for gender (adjusted HRR = 2.31; 95% CI 1.39-3.85) which was also
      diluted by the further adjustment for covariates that may also be mediators of
      the association (adjusted HRR = 1.80; 95% CI 1.08-3.01). CONCLUSION: Our study
      suggests that a history of work-related low back injury or taking time off work
      or having to perform light duties at work due to a work-related low back injury
      may be a risk factor for the development of troublesome LBP. Residual confounding
      may account for some of the observed associations, but this was less in the group
      who took time off work or had to work light duties due to a work-related low back
      injury.

PMID- 26208943
TI  - The first detection of Echinococcus multilocularis DNA in environmental fruit,
      vegetable, and mushroom samples using nested PCR.
AB  - The aim of this study was to estimate the presence of Echinococcus multilocularis
      DNA in fruits, vegetables, and mushrooms in rural areas of Varmia-Masuria
      Province, Poland, which is the region with the highest number of human alveolar
      echinococcosis (AE) cases in this country. Recovery tests showed that E.
      multilocularis DNA is detectable in samples contaminated with at least 100 eggs
      of this tapeworm. In total, 103 environmental fruit, vegetable, and mushroom
      samples collected in forests, plantations, and kitchen gardens were analyzed
      using nested PCR assay based on the mitochondrial 12S ribosomal RNA (rRNA) gene.
      The parasite DNA was detected in 23.3% of the samples. Sequencing confirmed that
      the obtained PCR products represented E. multilocularis. This study is the first
      environmental survey of the presence of E. multilocularis DNA in fruits,
      vegetables, and mushrooms intended for consumption. The results clearly
      demonstrate that it may be a direct source of human infections and shows the need
      to educate the public about the threat, especially people living in at-risk
      areas.

PMID- 26208944
TI  - Glioblastoma multiforme in the very elderly.
AB  - Glioblastoma is the most malignant and most common primary brain tumour and is
      treated with resection followed by post-operative radiotherapy and chemotherapy.
      However, a significant amount of patients are older than 80 years, and such an
      approach may not be appropriate. Data on patients aged 80 or older with
      glioblastoma from two hospitals was collected using the CNS Tumour Database on
      the Australian Comprehensive Cancer Outcomes and Research Database (ACCORD)
      system operated by BioGrid. Between 2008 and July 2011, 40 patients aged 80 years
      or older were diagnosed with glioblastoma. The median ECOG PS was 2 and the ASA
      score was 3. All 40 patients underwent surgery and 33% had a gross total
      resection. Only six patients (15%) had either post-operative radiotherapy or
      chemotherapy. The overall median survival was 4 months (range 0-18 months) and
      28% of patients lived between 6 and 24 months. This is the largest reported
      cohort of very elderly patients with glioblastoma. Patients tolerated surgery but
      few went on to receive post-operative radiotherapy or chemotherapy. This patient
      population requires special attention and in particular would benefit from
      participation in suitable clinical trials to determine the best care regime.

PMID- 26208945
TI  - Object-based representation and analysis of light and electron microscopic volume
      data using Blender.
AB  - BACKGROUND: Rapid improvements in light and electron microscopy imaging
      techniques and the development of 3D anatomical atlases necessitate new
      approaches for the visualization and analysis of image data. Pixel-based
      representations of raw light microscopy data suffer from limitations in the
      number of channels that can be visualized simultaneously. Complex electron
      microscopic reconstructions from large tissue volumes are also challenging to
      visualize and analyze. RESULTS: Here we exploit the advanced visualization
      capabilities and flexibility of the open-source platform Blender to visualize and
      analyze anatomical atlases. We use light-microscopy-based gene expression atlases
      and electron microscopy connectome volume data from larval stages of the marine
      annelid Platynereis dumerilii. We build object-based larval gene expression
      atlases in Blender and develop tools for annotation and coexpression analysis. We
      also represent and analyze connectome data including neuronal reconstructions and
      underlying synaptic connectivity. CONCLUSIONS: We demonstrate the power and
      flexibility of Blender for visualizing and exploring complex anatomical atlases.
      The resources we have developed for Platynereis will facilitate data sharing and
      the standardization of anatomical atlases for this species. The flexibility of
      Blender, particularly its embedded Python application programming interface,
      means that our methods can be easily extended to other organisms.

PMID- 26208947
TI  - Come together, right now....
AB  - Editing the genome using approaches like TALEN and siRNA are already well tested.
      The new kid on the block is CRISPR-Cas9. CRISPR-Cas9 is rapidly evolving with
      impressive refinements for specificity, eliminating off-target effects, and
      versatility. One can adjust constructs and conditions to produce opposite effects
      on the genome and for a specific purpose. The nuances of the system, the means to
      significantly reduce off-targeting, and numerous applications are now emerging
      rapidly. This B&B commentary looks forward into how the CRISPR-Cas9 tool might
      serve the CCN field. 

PMID- 26208946
TI  - Vemurafenib pharmacokinetics and its correlation with efficacy and safety in
      outpatients with advanced BRAF-mutated melanoma.
AB  - Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of
      metastatic BRAF (V600) -mutant melanoma. However, data on the
      pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this
      prospective, multicenter study was to explore the PK/PD relationship for
      vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine
      patients treated with single-agent vemurafenib were prospectively analyzed.
      Vemurafenib plasma concentration (n = 159) was measured at days 15, 30, 60, and
      90 after treatment initiation. Clinical and biological determinants (including
      plasma vemurafenib concentration) for efficacy and safety were assessed using
      Cox's model and multivariate stepwise logistic regression. Median progression
      free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 %
      CI] 2.0-6.0) and 11.0 (95% CI 7.0-16.0) months, respectively. Twenty-nine
      patients (49 %) experienced any grade >=3 toxicity and the most frequent grade
      >=2 toxicity was skin rash (37 %). Severe toxicities led to definitive
      discontinuation in seven patients (12 %). Grade >=2 skin rash was not
      statistically associated with better objective response at day 60 (p = 0.06) and
      longer PFS (hazard ratio 0.47; 95 % CI 0.21-1.08; p = 0.075). Grade >=2 skin rash
      was statistically increased in patients with ECOG  >= 1 (odds ratio 4.67; 95 % CI
      1.39-15.70; p = 0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was
      significantly associated with a shorter PFS (1.5 [0.5-5.5] vs. 4.5 [2
      undetermined] months, p = 0.029). Finally, vemurafenib concentration was
      significantly greater in patients developing grade >=2 rash (61.7 +/- 25.0 vs.
      36.3 +/- 17.9 mg/L, p < 0.0001). These results suggest that early plasma drug
      monitoring may help identify outpatients at high risk of non-response or grade >=
      2 skin rash.

PMID- 26208948
TI  - Thermal Inactivation of Feline Calicivirus in Pet Food Processing.
AB  - Extrusion is the most common manufacturing process used to produce heat-treated
      dry dog and cat food (pet food) for domestic use and international trade. Due to
      reoccurring outbreaks of notifiable terrestrial animal diseases and their impact
      on international trade, experiments were undertaken to demonstrate the
      effectiveness of heat-treated extruded pet food on virus inactivation. The impact
      of extrusion processing in a pet food matrix on virus inactivation has not been
      previously reported and very few inactivation studies have examined the thermal
      inactivation of viruses in complex food matrices. The feline calicivirus vaccine
      strain FCV F-9 was used as a surrogate model RNA virus pathogen. Small-scale heat
      inactivation experiments using animal-derived pet food raw materials showed that
      a > 4 log10 reduction (log10 R) in infectivity occurred at 70  degrees C prior to
      reaching the minimum extrusion manufacturing operating temperature of 100 
      degrees C. As anticipated, small-scale pressure studies at extrusion pressure
      (1.6 MPa) showed no apparent effect on FCV F-9 inactivation. Additionally, FCV F
      9 was shown not to survive the acidic conditions used to produce pet food
      palatants of animal origin that are typically used as a coating after the
      extrusion process.

PMID- 26208949
TI  - Hospitalized Pregnant Women Who Leave Against Medical Advice: Attributes and
      Reasons.
AB  - OBJECTIVES: To identify the contributing factors for discharge against medical
      advice (DAMA) among pregnant women in Sistan and Balouchestan Province,
      southeastern Iran. METHODS: This hospital-based case-control study included a
      total of 168 DAMA pregnant women and 191 pregnant women who left hospital with
      medical approval. The participants were recruited between August 2012 and August
      2013. Logistic regression models were used for data analysis. RESULTS: Factors
      that increased the chance of DAMA in pregnant women included older age, younger
      spouse age, low level of education, low income level and having a health
      insurance. History of DAMA in previous hospitalizations, referral from other
      clinics, emergency admission and admission advice from non-physician individuals
      for hospitalization, and giving birth at home during previous pregnancies, were
      associated with an increase in the risk of DAMA. The most common hospital-related
      reason for DAMA was the teaching environment of the hospital (26.2%) followed by
      hospital staff misconduct (23.8%) and overcrowding in the hospital wards (23.2%).
      The most frequent patient-related factors for DAMA were willingness of the
      patients to continue treatment at home (58.9%) and feeling relative improvement
      (58.3%). CONCLUSIONS FOR PRACTICE: We found that both hospital and patient
      related factors contribute to DAMA among pregnant women. Early identification of
      women at risk of DAMA and improvement of medical staff communication skills may
      decrease the occurrence of DAMA and improve health outcomes of pregnant women.

PMID- 26208950
TI  - Lab-on-a-chip-based PCR-RFLP assay for the confirmed detection of short-length
      feline DNA in food.
AB  - Wider availability but lack of legal market trades has given feline meat a high
      potential for use as an adulterant in common meat and meat products. However,
      mixing of feline meat or its derivatives in food is a sensitive issue, since it
      is a taboo in most countries and prohibited in certain religions such as Islam
      and Judaism. Cat meat also has potential for contamination with of severe acute
      respiratory syndrome, anthrax and hepatitis, and its consumption might lead to an
      allergic reaction. We developed a very short-amplicon-length (69 bp) PCR assay,
      authenticated the amplified PCR products by AluI-restriction digestion followed
      by its separation and detection on a lab-on-a-chip-based automated
      electrophoretic system, and proved its superiority over the existing long
      amplicon-based assays. Although it has been assumed that longer DNA targets are
      susceptible to breakdown under compromised states, scientific evidence for this
      hypothesis has been rarely documented. Strong evidence showed that shorter
      targets are more stable than the longer ones. We confirmed feline-specificity by
      cross-challenging the primers against 10 different species of terrestrial,
      aquatic and plant origins in the presence of a 141-bp site of an 18S rRNA gene as
      a universal eukaryotic control. RFLP analysis separated 43- and 26-bp fragments
      of AluI-digest in both the gel-image and electropherograms, confirming the
      original products. The tested detection limit was 0.01% (w/w) feline meat in
      binary and ternary admixed as well as meatball matrices. Shorter target, better
      stability and higher sensitivity mean such an assay would be valid for feline
      identification even in degraded specimens. 

PMID- 26208951
TI  - Endocrine Effects of Circadian Disruption.
AB  - Disruption of circadian rhythms, provoked by artificial lighting at night,
      inconsistent sleep-wake schedules, and transmeridian air travel, is increasingly
      prevalent in modern society. Desynchrony of biological rhythms from environmental
      light cycles has dramatic consequences for human health. In particular,
      disrupting homeostatic oscillations in endocrine tissues and the hormones that
      these tissues regulate can have cascading effects on physiology and behavior.
      Accumulating evidence suggests that chronic disruption of circadian organization
      of endocrine function may lead to metabolic, reproductive, sleep, and mood
      disorders. This review discusses circadian control of endocrine systems and the
      consequences of distorting rhythmicity of these systems. 

PMID- 26208953
TI  - Measurements from preterm infants to guide face mask size.

PMID- 26208952
TI  - Contact lens care solution killing efficacy against Acanthamoeba castellanii by
      in vitro testing and live-imaging.
AB  - In the past decade there has been an increased incidence of Acanthamoeba
      keratitis, particularly in contact lens wearers. The aim of this study was to
      utilize in vitro killing assays and to establish a novel, time-lapse, live-cell
      imaging methodology to demonstrate the efficacy of contact lens care solutions in
      eradicating Acanthamoeba castellanii (A. castellanii) trophozoites and cysts.
      Standard qualitative and quantitative in vitro assays were performed along with
      novel time-lapse imaging coupled with fluorescent dye staining that signals cell
      death. Quantitative data obtained demonstrated that 3% non-ophthalmic hydrogen
      peroxide demonstrated the highest percent killing at 87.4% corresponding to a 4.4
      log kill. The other contact lens care solutions which showed a 72.9 to 29.2%
      killing which was consistent with 4.3-2.8 log reduction in trophozoite viability.
      Both analytical approaches revealed that polyquaternium/PHMB-based was the least
      efficacious in terms of trophicidal activity. The cysticidal activity of the
      solutions was much less than activity against trophozoites and frequently was not
      detected. Live-imaging provided a novel visual endpoint for characterizing the
      trophocidal activity of the care solutions. All solutions caused rapid rounding
      or pseudocyst formation of the trophozoites, reduced motility and the appearance
      of different morphotypes. Polyquaternium/alexidine-based and peroxide-based lens
      care system induced the most visible damage indicated by significant accumulation
      of debris from ruptured cells. Polyquaternium/PHMB-based was the least effective
      showing rounding of the cells but minimal death. These observations are in
      keeping with care solution biocides having prominent activity at the plasma
      membrane of Acanthamoeba.

PMID- 26208955
TI  - Antibacterial constituents of Neohyptis paniculata.
AB  - A new alpha-pyrone, 6R-[5R,6S-diacetyloxy-1Z,3E-heptadienyl]-5,6-dihydro-2H-pyran
      2one (1), along with six known compounds including an alpha-pyrone, flavones and
      terpenes was isolated from the aerial parts of Neohyptis paniculata. The
      structure of 1 was established unambiguously by MS and a series of 1D and 2D-NMR
      spectroscopic analyses. The antibacterial activity of the compounds (1-7) was
      investigated against five strains of multi-drug resistant (MDR) and methicillin
      resistant Staphylococcus aureus and minimum inhibitory concentrations (MICs) of
      these compounds were found to be in the range of 64-256 MUg/mL.

PMID- 26208954
TI  - Potential for a paradigm change in the detection of retinopathy of prematurity
      requiring treatment.

PMID- 26208956
TI  - Bovid ecomorphology and hominin paleoenvironments of the Shungura Formation,
      lower Omo River Valley, Ethiopia.
AB  - The Shungura Formation in the lower Omo River Valley, southern Ethiopia, has
      yielded an important paleontological and archeological record from the Pliocene
      and Pleistocene of eastern Africa. Fossils are common throughout the sequence and
      provide evidence of paleoenvironments and environmental change through time. This
      study developed discriminant function ecomorphology models that linked astragalus
      morphology to broadly defined habitat categories (open, light cover, heavy cover,
      forest, and wetlands) using modern bovids of known ecology. These models used
      seven variables suitable for use on fragmentary fossils and had overall
      classification success rates of >82%. Four hundred and one fossils were analyzed
      from Shungura Formation members B through G (3.4-1.9 million years ago). Analysis
      by member documented the full range of ecomorph categories, demonstrating that a
      wide range of habitats existed along the axis of the paleo-Omo River. Heavy cover
      ecomorphs, reflecting habitats such as woodland and heavy bushland, were the most
      common in the fossil sample. The trend of increasing open cover habitats from
      Members C through F suggested by other paleoenvironmental proxies was documented
      by the increase in open habitat ecomorphs during this interval. However, finer
      grained analysis demonstrated considerable variability in ecomorph frequencies
      over time, suggesting that substantial short-term variability is masked when
      grouping samples by member. The hominin genera Australopithecus, Homo, and
      Paranthropus are associated with a range of ecomorphs, indicating that all three
      genera were living in temporally variable and heterogeneous landscapes.
      Australopithecus finds were predominantly associated with lower frequencies of
      open habitat ecomorphs, and high frequencies of heavy cover ecomorphs, perhaps
      indicating a more woodland focus for this genus. 

PMID- 26208958
TI  - Comment: Yet another "disconnect" between amyloid and Alzheimer disease?

PMID- 26208957
TI  - Rapid progression of familial amyloidotic polyneuropathy: a multinational natural
      history study.
AB  - OBJECTIVES: To assess the association between severity of neuropathy and disease
      stage, and estimate the rate of neuropathy progression in a retrospective cross
      sectional analysis of a multinational population of patients with familial
      amyloidotic polyneuropathy (FAP). METHODS: We characterize neuropathy severity
      and rate of progression in available patients with FAP in France, the United
      States, Portugal, and Italy. Neuropathy Impairment Scores (NIS), time from
      symptom onset to NIS measurement, polyneuropathy disability (PND) scores, FAP
      disease stage, and manual grip strength data were collected. We estimated
      neuropathy progression using Loess Fit and Gompertz Fit models. RESULTS: For the
      283 patients studied (mean age, 56.4 years), intercountry genotypic variation in
      the transthyretin (TTR) mutation was observed, with the majority of patients in
      Portugal (92%) having early-onset Val30Met-FAP. There was also marked
      intercountry variation in PND score, FAP stage, and TTR stabilizer use. NIS was
      associated with PND score (NIS 10 and 99 for scores I and IV, respectively; p <
      0.0001) and FAP stage (NIS 14 and 99 for stages 1 and 3, respectively; p <
      0.0001). In addition, there was an association between NIS and TTR genotype. The
      estimated rate of NIS progression for a population with a median NIS of 32 was
      14.3 points/year; the corresponding estimated rate for the modified NIS+7 is 17.8
      points/year. CONCLUSIONS: In a multinational population of patients with FAP,
      rapid neuropathic progression is observed and the severity of neuropathy is
      associated with functional scales of locomotion.

PMID- 26208960
TI  - Multisystem proteinopathy: intersecting genetics in muscle, bone, and brain
      degeneration.

PMID- 26208961
TI  - SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles.
AB  - OBJECTIVE: To identify the genetic etiology and characterize the
      clinicopathologic features of a novel distal myopathy. METHODS: We performed
      whole-exome sequencing on a family with an autosomal dominant distal myopathy and
      targeted exome sequencing in 1 patient with sporadic distal myopathy, both with
      rimmed vacuolar pathology. We also evaluated the pathogenicity of identified
      mutations using immunohistochemistry, Western blot analysis, and expression
      studies. RESULTS: Sequencing identified a likely pathogenic c.1165+1 G>A splice
      donor variant in SQSTM1 in the affected members of 1 family and in an unrelated
      patient with sporadic distal myopathy. Affected patients had late-onset distal
      lower extremity weakness, myopathic features on EMG, and muscle pathology
      demonstrating rimmed vacuoles with both TAR DNA-binding protein 43 and SQSTM1
      inclusions. The c.1165+1 G>A SQSTM1 variant results in the expression of 2
      alternatively spliced SQSTM1 proteins: 1 lacking the C-terminal PEST2 domain and
      another lacking the C-terminal ubiquitin-associated (UBA) domain, both of which
      have distinct patterns of cellular and skeletal muscle localization. CONCLUSIONS:
      SQSTM1 is an autophagic adaptor that shuttles aggregated and ubiquitinated
      proteins to the autophagosome for degradation via its C-terminal UBA domain.
      Similar to mutations in VCP, dominantly inherited mutations in SQSTM1 are now
      associated with rimmed vacuolar myopathy, Paget disease of bone, amyotrophic
      lateral sclerosis, and frontotemporal dementia. Our data further suggest a
      pathogenic connection between the disparate phenotypes.

PMID- 26208963
TI  - Comment: Chemoradiotherapy for glioblastoma patients--the double-edged sword.

PMID- 26208962
TI  - Poor early relapse recovery affects onset of progressive disease course in
      multiple sclerosis.
AB  - OBJECTIVE: To evaluate the relationship between early relapse recovery and onset
      of progressive multiple sclerosis (MS). METHODS: We studied a population-based
      cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive
      MS) and a clinic-based cohort (415 patients with bout-onset progressive MS),
      excluding patients with primary progressive MS. Bout-onset progressive MS
      includes patients with single-attack progressive and secondary progressive MS.
      "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit
      of the relapse improved completely or almost completely (patient-reported and
      examination-confirmed outcome measured >=6 months post relapse). Impact of
      initial relapse recovery and first 5-year average relapse recovery on cumulative
      incidence of progressive MS was studied accounting for patients yet to develop
      progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of
      initial relapse recovery on time to progressive MS onset was also studied in the
      clinic-based cohort with already-established progressive MS (t test). RESULTS: In
      the population-based cohort, 153 patients (80.1%) had on average good recovery
      from first 5-year relapses, whereas 30 patients (15.7%) had on average poor
      recovery. Half of the good recoverers developed progressive MS by 30.2 years
      after MS onset, whereas half of the poor recoverers developed progressive MS by
      8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery
      from the first relapse alone was also associated with a delay in progressive
      disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p =
      0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery
      from the initial relapse. CONCLUSIONS: Patients with MS with poor recovery from
      early relapses will develop progressive disease course earlier than those with
      good recovery.

PMID- 26208965
TI  - Patient mobility in the context of austerity and an enlarged EU: The European
      Court of Justice's ruling in the Petru Case.
AB  - Since 1998, the European Court of Justice (EUCJ) has established a set of
      principles concerning patient mobility across Member States. At present, these
      principles are challenged against a new background, i.e., an enlarged EU and
      austerity-driven measures in the field of healthcare. This is even more relevant
      in view of the significant differences between countries and between services on
      healthcare access. In the Petru case, a Romanian woman sought healthcare in
      Germany due to an alleged lack of basic infrastructure in her local Romanian
      hospital. A crucial question arises in this context of whether the patient's
      interests (i.e., right to cross-border healthcare) or the Member State's
      interests (i.e., financial stability of the healthcare system) prevail. We
      analyse this case and its implications for future patient mobility. From the
      point of view of patients, the EUCJ's decision implies that also a lack of
      medication and basic medical supplies can be claimed as "undue delay", however
      for Member States it is sufficient to provide quality treatments in at least one
      hospital. Although the Court has provided a solution for the Petru case, we argue
      that major challenges remain, such as the definition of the international state
      of-the-art or other limitations to reductions of the health basket. 

PMID- 26208964
TI  - Standard chemoradiation for glioblastoma results in progressive brain volume
      loss.
AB  - OBJECTIVE: To investigate the effects of chemotherapy and cranial irradiation on
      normal brain tissue using in vivo neuroimaging in patients with glioblastoma.
      METHODS: We used longitudinal MRI to monitor structural brain changes during
      standard treatment in patients newly diagnosed with glioblastoma. We assessed
      volumetric and diffusion tensor imaging measures in 14 patients receiving 6 weeks
      of chemoradiation, followed by up to 6 months of temozolomide chemotherapy alone.
      We examined changes in whole brain, gray matter (GM), white matter (WM), anterior
      lateral ventricle, and hippocampal volumes. Normal-appearing GM, WM, and
      hippocampal analyses were conducted within the hemisphere of lowest/absent tumor
      burden. We examined diffusion tensor imaging measures within the subventricular
      zone. RESULTS: Whole brain (F = 2.41; p = 0.016) and GM (F = 2.13; p = 0.036)
      volume decreased during treatment, without significant WM volume change. Anterior
      lateral ventricle volume increased significantly (F = 65.51; p < 0.001). In
      participants analyzed beyond 23 weeks, mean ventricular volume increased by 42.2%
      (SE: 8.8%; t = 4.94; p < 0.005). Apparent diffusion coefficient increased within
      the subventricular zone (F = 7.028; p < 0.001). No significant changes were
      identified in hippocampal volume. CONCLUSIONS: We present evidence of significant
      and progressive treatment-associated structural brain changes in patients with
      glioblastoma treated with standard chemoradiation. Future studies using
      longitudinal neuropsychological evaluation are needed to characterize the
      functional consequences of these structural changes.

PMID- 26208966
TI  - Effect of guanidine hydrochloride and urea on the interaction of 6-thioguanine
      with human serum albumin: a spectroscopic and molecular dynamics based study.
AB  - 6-thioguanine (6-TG) is an antineoplastic, nucleobase guanine, purine analog drug
      belongs to thiopurine drug-family of antimetabolites. In the present study, we
      report an experimental approach towards interaction mechanism of 6-TG with human
      serum albumin (HSA) and examine the chemical stability of HSA in the presence of
      denaturants such as guanidine hydrochloride (GdnHCl) and urea. Interaction of 6
      TG with HSA has been studied by various spectroscopic and spectropolarimeteric
      methods to investigate what short of binding occurs at physiological conditions.
      6-TG binds in the hydrophobic cavity of subdomain IIA of HSA by static quenching
      mechanism which induces conformation alteration in the protein structure. That
      helpful for further study of denaturation process where change in secondary
      structures causes unfolding of protein that also responsible for severance of
      domain III from rest of the protein part. We have also performed molecular
      simulation and molecular docking study in the presence of denaturating agents to
      determine the binding property of 6-TG and the effect of denaturating agents on
      the structural activity of HSA. We had found that GdnHCl is more effective
      denaturating agent when compared to urea. Hence, this study provides straight
      evidence of the binding mechanism of 6-TG with HSA and the formation of
      intermediate or unfolding transition that causes unfolding of HSA. 

PMID- 26208968
TI  - Scientific and Regulatory Policy Committee Review: Review of the Organisation for
      Economic Co-operation and Development (OECD) Guidance on the GLP Requirements for
      Peer Review of Histopathology.
AB  - In 2014, the Organisation for Economic Co-operation and Development (OECD) issued
      guidance no. 16, Guidance on the GLP Requirements for Peer Review of
      Histopathology. The stated purpose of the guidance document is "to provide
      guidance to pathologists, test facility management, study directors and quality
      assurance personnel on how the peer review of histopathology should be planned,
      managed, documented, and reported in order to meet Good Laboratory Practice (GLP)
      expectations and requirements." On behalf of and in collaboration with the global
      societies of toxicologic pathology, the Society of Toxicologic Pathology
      initiated a review of OECD guidance no. 16. The objectives of this review are to
      provide a unified interpretation of the guidance, to recommend compliant
      processes for organizations to implement, and to avoid inconsistent process
      adaptations across the industry. This review of the guidance document is the
      product of a global collaboration with other societies of toxicologic pathology
      and provides a section-by-section international consensus view and interpretation
      of the OECD guidance on peer review. 

PMID- 26208969
TI  - MHC in a monogamous lizard--Characterization of class I MHC genes in the
      Australian skink Tiliqua rugosa.
AB  - The major histocompatibility complex (MHC) is a highly variable region of
      vertebrate genomes that encodes cellular proteins involved in the immune
      response. In addition to the benefits of MHC research in understanding the
      genetic basis of host resistance to disease, the MHC is an ideal candidate for
      studying genetic diversity under strong natural selection. However, the MHC of
      many non-model vertebrate taxa are poorly characterized, hindering an
      understanding of disease resistance and its application to conservation genetics
      in these groups. Squamates (lizards and snakes) remain particularly
      underrepresented despite their being the most diverse order of non-avian
      sauropsids. We characterized MHC class I sequence diversity from an Australian
      skink, the sleepy lizard (Tiliqua rugosa), using both cDNA and genomic sequence
      data and also present genomic class I sequences from the related skinks Tiliqua
      adelaidensis and Egernia stokesii. Phylogenetic analysis of Tiliqua and other
      published sqamate MHC class I sequences suggest that MHC diverged very early in
      Tiliqua compared with the other studied squamates. We identified at least 4
      classical MHC class I loci in T. rugosa and also shared polymorphism among T.
      rugosa, T. adelaidensis and E. stokesii in the sequences encoding peptide-binding
      alpha1 and alpha2 domains.

PMID- 26208967
TI  - Taurine: the appeal of a safe amino acid for skeletal muscle disorders.
AB  - Taurine is a natural amino acid present as free form in many mammalian tissues
      and in particular in skeletal muscle. Taurine exerts many physiological
      functions, including membrane stabilization, osmoregulation and cytoprotective
      effects, antioxidant and anti-inflammatory actions as well as modulation of
      intracellular calcium concentration and ion channel function. In addition taurine
      may control muscle metabolism and gene expression, through yet unclear
      mechanisms. This review summarizes the effects of taurine on specific muscle
      targets and pathways as well as its therapeutic potential to restore skeletal
      muscle function and performance in various pathological conditions. Evidences
      support the link between alteration of intracellular taurine level in skeletal
      muscle and different pathophysiological conditions, such as disuse-induced muscle
      atrophy, muscular dystrophy and/or senescence, reinforcing the interest towards
      its exogenous supplementation. In addition, taurine treatment can be beneficial
      to reduce sarcolemmal hyper-excitability in myotonia-related syndromes. Although
      further studies are necessary to fill the gaps between animals and humans, the
      benefit of the amino acid appears to be due to its multiple actions on cellular
      functions while toxicity seems relatively low. Human clinical trials using
      taurine in various pathologies such as diabetes, cardiovascular and neurological
      disorders have been performed and may represent a guide-line for designing
      specific studies in patients of neuromuscular diseases. 

PMID- 26208970
TI  - 'From activating towards caring': shifts in care approaches at the end of life of
      people with intellectual disabilities; a qualitative study of the perspectives of
      relatives, care-staff and physicians.
AB  - BACKGROUND: Professionals and relatives increasingly have to deal with people
      with intellectual disabilities (ID) who are in need of end-of-life care. This is
      a specific type of care that may require a different approach to the focus on
      participation that currently characterizes the care for people with ID. This
      paper describes the shifts in care approaches and attitudes that relatives and
      professionals perceive as the death of a person with ID approaches, as well as
      the values underlying these shifts. METHODS: A qualitative design was used to
      reconstruct the cases of twelve recently deceased people with ID. Relatives and
      professionals who were closest to the person at the end of their life were
      interviewed. Interviews were transcribed verbatim and data were analyzed
      inductively, using elements of thematic analysis. RESULTS: Five shifts were
      found: 1) adapting to a new strategy of comforting care, taking over tasks and
      symptom relief, 2) interweaving of emotional and professional involvement, 3)
      stronger reliance on the joint interpretation of signals expressing distress and
      pain, 4) magnified feeling of responsibility in medical decisions, 5) intensified
      caring relationship between 'two families': relatives and care staff. Six
      relational values were behind these shifts: 'being there' for the person with ID,
      'being responsive' to the person's needs, 'reflection' on their own emotions and
      caring relationships, 'attentiveness' to the ID person's wishes and expressions
      of distress, 'responsibility' for taking joint decisions in the best interests of
      the person, and 'openness to cooperation and sharing' the care with others.
      CONCLUSIONS: End-of-life care for people with ID involves curtailing expectations
      of participation and skill acquirement, and an increase in teamwork featuring
      intensified comforting care, symptom management and medical decision making.
      Three caring relationships need to be fostered: the relationship with the person
      with ID, relationships among professionals and the relationship between relatives
      and professionals. ID care services should invest particularly in the emotional
      support and expertise level of care staff, and in the collaboration between
      relatives and professionals.

PMID- 26208971
TI  - A novel compound heterozygous mutation in a Chinese boy with L-2-hydroxyglutaric
      aciduria: a case study.
AB  - BACKGROUND: L-2-hydroxyglutaric aciduria is a rare autosomal recessive
      encephalopathy caused by mutations in the L-2-hydroxyglutarate dehydrogenase
      gene. We describe some novel clinical and molecular characteristics found in a
      boy with L-2-hydroxyglutaric aciduria. CASE PRESENTATION: We report an 8-year-old
      Chinese boy, who had characteristic developmental delay, ataxia and acrocephaly
      as the main symptoms. He also complained of paroxysmal headache and palpitation.
      Brain image revealed a symmetrical, extensive subcortical white matter lesion.
      Urine test for organic acids showed a significantly increased level of 2
      hydroxyglutaric acid (106.74 mmol/mol cre, normal range 0.6 ~ 5.9 mmol/mol cre),
      leading to the diagnosis of L-2-hydroxyglutaric aciduria. Genetic testing
      uncovered two heterozygous missense mutations in L-2-hydroxyglutarate
      dehydrogenase gene: c.169G > A in exon 2 and c.542G > T in exon 5, not hitherto
      been described. CONCLUSION: Novel gene mutation and associated clinical symptoms
      can contribute for the understanding and identification of this rare disease.
      Possible genotype-phenotype correlation waits for further study.

PMID- 26208972
TI  - Mouse anatomy ontologies: enhancements and tools for exploring and integrating
      biomedical data.
AB  - Mouse anatomy ontologies provide standard nomenclature for describing normal and
      mutant mouse anatomy, and are essential for the description and integration of
      data directly related to anatomy such as gene expression patterns. Building on
      our previous work on anatomical ontologies for the embryonic and adult mouse, we
      have recently developed a new and substantially revised anatomical ontology
      covering all life stages of the mouse. Anatomical terms are organized in complex
      hierarchies enabling multiple relationships between terms. Tissue classification
      as well as partonomic, developmental, and other types of relationships can be
      represented. Hierarchies for specific developmental stages can also be derived.
      The ontology forms the core of the eMouse Atlas Project (EMAP) and is used
      extensively for annotating and integrating gene expression patterns and other
      data by the Gene Expression Database (GXD), the eMouse Atlas of Gene Expression
      (EMAGE) and other database resources. Here we illustrate the evolution of the
      developmental and adult mouse anatomical ontologies toward one combined system.
      We report on recent ontology enhancements, describe the current status, and
      discuss future plans for mouse anatomy ontology development and application in
      integrating data resources.

PMID- 26208974
TI  - Where the latest US dietary guidelines are heading.

PMID- 26208973
TI  - Principles and application of LIMS in mouse clinics.
AB  - Large-scale systemic mouse phenotyping, as performed by mouse clinics for more
      than a decade, requires thousands of mice from a multitude of different mutant
      lines to be bred, individually tracked and subjected to phenotyping procedures
      according to a standardised schedule. All these efforts are typically organised
      in overlapping projects, running in parallel. In terms of logistics, data
      capture, data analysis, result visualisation and reporting, new challenges have
      emerged from such projects. These challenges could hardly be met with traditional
      methods such as pen & paper colony management, spreadsheet-based data management
      and manual data analysis. Hence, different Laboratory Information Management
      Systems (LIMS) have been developed in mouse clinics to facilitate or even enable
      mouse and data management in the described order of magnitude. This review shows
      that general principles of LIMS can be empirically deduced from LIMS used by
      different mouse clinics, although these have evolved differently. Supported by
      LIMS descriptions and lessons learned from seven mouse clinics, this review also
      shows that the unique LIMS environment in a particular facility strongly
      influences strategic LIMS decisions and LIMS development. As a major conclusion,
      this review states that there is no universal LIMS for the mouse research domain
      that fits all requirements. Still, empirically deduced general LIMS principles
      can serve as a master decision support template, which is provided as a hands-on
      tool for mouse research facilities looking for a LIMS. 

PMID- 26208976
TI  - Management of full-thickness rotator cuff tears: appropriate use criteria.
AB  - BACKGROUND: The appropriate use criteria (AUC) were developed for full-thickness
      rotator cuff tears to determine when it is reasonable to recommend nonoperative
      care, partial repair/debridement, repair, reconstruction, or arthroplasty. The
      goal of this report was to interpret and summarize the results of the AUC process
      into clinically relevant terms. METHODS: Using the results of the AUC
      methodology, we systematically interpreted the clinical importance attributed to
      the various patient and pathologic variables. We then assessed the combination of
      considerations that would justify the various treatment options using "preference
      tables." RESULTS: A nonoperative program was appropriate if the patient had a
      positive response to conservative care. However, a repair could be maybe
      appropriate was also accepted. Rotator cuff repair was appropriate when
      conservative treatment failed in symptomatic patients. Reconstructive measures
      were recognized primarily in those with chronic massive tears. Most found
      arthroplasty maybe appropriate only in healthy patients, pseudoparalysis, and
      chronic massive tears. Surprisingly, neither factors that decreased healing nor
      adversely affected outcome had a strong influence on the panel's treatment
      recommendations. CONCLUSIONS: The AUC process accounts for clinical experience
      and considers individual patient and pathologic characteristics of the condition.
      Overall, the outcome of this exercise does support the current practice for the
      management of rotator cuff tears (ie, repair of symptomatic tears). However, the
      minimal importance given to patient and pathologic considerations, well
      documented to influence outcome, prompts an ongoing effort to refine this
      important and clinically relevant process.

PMID- 26208975
TI  - Targeting IL13Ralpha2 activates STAT6-TP63 pathway to suppress breast cancer lung
      metastasis.
AB  - INTRODUCTION: Basal-like breast cancer (BLBC) is an aggressive subtype often
      characterized by distant metastasis, poor patient prognosis, and limited
      treatment options. Therefore, the discovery of alternative targets to restrain
      its metastatic potential is urgently needed. In this study, we aimed to identify
      novel genes that drive metastasis of BLBC and to elucidate the underlying
      mechanisms of action. METHODS: An unbiased approach using gene expression
      profiling of a BLBC progression model and in silico leveraging of pre-existing
      tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral
      mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with
      whole-body in vivo bioluminescence imaging was performed to assess its role in
      regulating breast cancer tumor growth and lung metastasis. Gene expression
      microarray analysis was followed by in vitro validation and cell migration assays
      to elucidate the downstream molecular pathways involved in this process. RESULTS:
      We found that overexpression of the decoy receptor IL13Ralpha2 is significantly
      enriched in basal compared with luminal primary breast tumors as well as in a
      subset of metastatic basal-B breast cancer cells. Importantly, breast cancer
      patients with high-grade tumors and increased IL13Ralpha2 levels had
      significantly worse prognosis for metastasis-free survival compared with patients
      with low expression. Depletion of IL13Ralpha2 in metastatic breast cancer cells
      modestly delayed primary tumor growth but dramatically suppressed lung metastasis
      in vivo. Furthermore, IL13Ralpha2 silencing was associated with enhanced IL-13
      mediated phosphorylation of signal transducer and activator of transcription 6
      (STAT6) and impaired migratory ability of metastatic breast cancer cells.
      Interestingly, genome-wide transcriptional analysis revealed that IL13Ralpha2
      knockdown and IL-13 treatment cooperatively upregulated the metastasis suppressor
      tumor protein 63 (TP63) in a STAT6-dependent manner. These observations are
      consistent with increased metastasis-free survival of breast cancer patients with
      high levels of TP63 and STAT6 expression and suggest that the STAT6-TP63 pathway
      could be involved in impairing metastatic dissemination of breast cancer cells to
      the lungs. CONCLUSION: Our findings indicate that IL13Ralpha2 could be used as a
      promising biomarker to predict patient outcome and provide a rationale for
      assessing the efficacy of anti-IL13Ralpha2 therapies in a subset of highly
      aggressive basal-like breast tumors as a strategy to prevent metastatic disease.

PMID- 26208977
TI  - Experimental validation of methods for differential gene expression analysis and
      sample pooling in RNA-seq.
AB  - BACKGROUND: Massively parallel cDNA sequencing (RNA-seq) experiments are
      gradually superseding microarrays in quantitative gene expression profiling.
      However, many biologists are uncertain about the choice of differentially
      expressed gene (DEG) analysis methods and the validity of cost-saving sample
      pooling strategies for their RNA-seq experiments. Hence, we performed
      experimental validation of DEGs identified by Cuffdiff2, edgeR, DESeq2 and Two
      stage Poisson Model (TSPM) in a RNA-seq experiment involving mice amygdalae micro
      punches, using high-throughput qPCR on independent biological replicate samples.
      Moreover, we sequenced RNA-pools and compared their results with sequencing
      corresponding individual RNA samples. RESULTS: False-positivity rate of Cuffdiff2
      and false-negativity rates of DESeq2 and TSPM were high. Among the four
      investigated DEG analysis methods, sensitivity and specificity of edgeR was
      relatively high. We documented the pooling bias and that the DEGs identified in
      pooled samples suffered low positive predictive values. CONCLUSIONS: Our results
      highlighted the need for combined use of more sensitive DEG analysis methods and
      high-throughput validation of identified DEGs in future RNA-seq experiments. They
      indicated limited utility of sample pooling strategies for RNA-seq in similar
      setups and supported increasing the number of biological replicate samples.

PMID- 26208978
TI  - Ecological correlation between diabetes hospitalizations and fine particulate
      matter in Italian provinces.
AB  - BACKGROUND: Exposure to particulate matter has been associated with increased
      risk of cardiovascular and respiratory diseases. We evaluated the ecological
      correlation between standardized hospital discharges with diabetes in Italian
      provinces and fine particulate matter (PM2.5) adjusting for common risk factors,
      socioeconomic factors and differences in hospitalization appropriateness.
      METHODS: We used cross sectional data aggregated at the province level and
      available from official institutional databases for years 2008-2010. Covariates
      included prevalence of adult overweight, obese, smokers, physically inactive,
      education and income (as average gross domestic product per person, GDP). We
      reduced the number of covariates to a smaller number of factors for the
      subsequent statistical model by extracting meaningful components using principal
      component analysis (PCA). Log-linear multiple regression analysis was used to
      model diabetes hospital discharges with PCA components and PM2.5 levels and
      hospitalization appropriateness for men and women. RESULTS: The first PCA
      components for both men and women were characterized by larger loadings of risk
      factors (obesity, overweight, physical inactivity, cigarette smoking) and lower
      socioeconomic factors (educational level and mean GDP). Diabetes hospitalization
      increases with the first PCA component and decreases with the index of
      hospitalization appropriateness. In fully adjusted models, diabetes
      hospitalizations increase with increasing annual PM2.5 concentrations, with a
      rise of 3.5 % (1.3 %-5.6 %) for men and of 4.0 % (1.5 %-6.4 %) for women per unit
      of PM2.5 increase. CONCLUSIONS: We found a significant ecological relationship
      between sex and age standardised hospital discharge with diabetes as principle
      diagnosis and mean annual PM2.5 concentrations in Italian provinces, once that
      covariates have been accounted for. The relationship was robust to different
      means of estimating PM2.5 exposure. A large portion of the variance of diabetes
      hospitalizations was linked to differences of hospital care appropriateness
      between Italian regions and this variable should routinely be included in
      ecological analyses of hospitalizations.

PMID- 26208979
TI  - Lowered cutoff of lymph node fine-needle aspiration thyroglobulin in thyroid
      cancer patients with serum anti-thyroglobulin antibody.
AB  - OBJECTIVE: Fine needle aspiration cytology (FNAC) and measurement of
      thyroglobulin (Tg) in needle washout (FNA-Tg) are recommended for the diagnosis
      of metastatic or recurrent lymph nodes (LNs) in differentiated thyroid cancer
      (DTC). However, the effect of serum Tg antibody (TgAb) on FNA-Tg levels still
      remains unclear in the preoperative setting. We analyze the interference of serum
      TgAb on FNA-Tg levels as proof of concept in the diagnostic advantage of serum
      TgAb combined with FNA-Tg. SUBJECTS AND METHODS: A total of 370 suspicious
      cervical LNs from 273 patients with DTC were included. The primary tumor was
      confirmed as DTC on preoperative pathology in all patients. We performed FNA-Tg
      measurement and FNAC on suspicious LNs and evaluated the diagnostic performance
      of FNAC and FNA-Tg according to TgAb status. Final diagnoses were confirmed by
      histological examination of excised specimens or by follow-up ultrasonography for
      at least 6 months. RESULTS: Data from 273 subjects with suspicious 370 LNs were
      evaluated. Fifty-five LNs (14.9%) were from TgAb+ positive serum TgAb (TgAb+)
      patients. Serum Tg and FNA-Tg levels were significantly lower in patients with
      TgAb+ than in those with TgAb-negative (TgAb-). Final pathology confirmed 109 LNs
      (29.5%) as malignant. Diagnostic performance of FNA-Tg at the same cutoff level
      was lower in the TgAb+ than TgAb- group. FNA-Tg cutoff levels determined by ROC
      curve were lower in the TgAb+ group. CONCLUSION: The results suggested that the
      cutoff value of FNA-Tg should be lowered in suspicious LN before thyroidectomy in
      thyroid cancer patients with TgAb.

PMID- 26208980
TI  - Parental separation in childhood, social capital, and suicide thoughts and
      suicide attempts: A population-based study.
AB  - Studies of the association between parental separation in childhood and suicide
      thoughts and attempts are scarce. The aim of this study is to investigate
      associations between parental separation/divorce during childhood, and ever
      having had suicide thoughts and ever having made suicide attempt, adjusting for
      social capital and other covariates. In 2012 a cross-sectional public health
      survey was conducted in Scania, southern Sweden, with a postal questionnaire with
      28,029 participants aged 18-80. Associations between parental separation/divorce
      during childhood and ever having considered suicide or having made suicide
      attempt were analysed by logistic regression. Overall, 12.1% of the men and 15.5%
      of the women had experienced suicide thoughts, and 3.2% of the men and 5.3% of
      the women had ever tried committing suicide. Among men, 20.4% had experienced
      parental separation during childhood until age 18, and among women 22.3%.
      Parental separation/divorce in childhood was with few exceptions significantly
      associated with ever having had suicide thoughts with the highest odds ratios for
      those who had experienced parental separation during ages 0-4 years. Parental
      separation/divorce in childhood was significantly associated with suicide
      attempts among men who had experienced parental separation/divorce at ages 0-4
      and 15-18, and among women at any age 0-18. 

PMID- 26208981
TI  - The functional exercise capacity in patients with bipolar disorder versus healthy
      controls: A pilot study.
AB  - The aim of the current study was to compare the functional exercise capacity of
      patients with bipolar disorder with age-, gender- and body mass index (BMI)
      matched healthy controls. Thirty patients (16 ?, 40.8+/-11.6 years) and healthy
      controls (16 ?, 40.5+/-10.8 years) were included. All participants performed a 6
      min walk test to assess the functional exercise capacity and completed the
      International Physical Activity Questionnaire. Patients were screened for
      psychiatric symptoms using the Quick Inventory of Depressive Symptomatology and
      Hypomania Checklist-32. Results demonstrated that patients with bipolar disorder
      demonstrated a significantly poorer functional exercise capacity (590.8+/-112.6
      versus 704.2+/-94.3m). A backward stepwise regression analyses showed that the
      level of depression and existing foot or ankle static problems and back pain
      before the test explained 70.9% of the variance in the distance achieved on the 6
      min walk test (functional exercise capacity). The current study demonstrates that
      foot and back pain appear to be important negative predictors of functional
      exercise capacity in patients with bipolar disorder. Physical activity
      interventions delivered by physical therapists may help ameliorate pain symptoms
      and improve functional exercise capacity. 

PMID- 26208982
TI  - Association between haemorrhages and treatment with selective and non-selective
      serotonergic antidepressants: Possible implications of quantitative signal
      detection.
AB  - Inhibition of serotonin uptake in platelets seems to be the crucial mechanism
      underlying SSRI-associated haemorrhages. This effect is also present in
      antidepressants featuring non-selective serotonin reuptake inhibition (non-SSRI).
      Impact of selectivity of serotonin reuptake and/or affinity to the serotonin
      reuptake transporter on the bleeding risk have not yet been studied sufficiently.
      We retrieved country- and SSRI-/non-SSRI-specific data from the Uppsala
      Monitoring Centre and used a case/non-case approach to calculate substance
      specific reporting odds ratios (ROR) to evaluate the statistical association of
      treatment with SSRI/non-SSRI and haemorrhages. Country-specific analysis revealed
      no clear trends towards an increased risk of bleeding related to particular
      agents of group SSRI/non-SSRI (sporadically ROR>1 for citalopram, duloxetine,
      escitalopram, fluvoxamine, paroxetine, sertraline, St. John's wort). There was a
      clear trend in the total dataset towards a "reduced protective effect" (suggested
      by ROR<1) on the development of haemorrhages with agents featuring comparatively
      high affinity to the 5-HTT and/or selective serotonin reuptake inhibition (as
      with escitalopram, citalopram, duloxetine or venlafaxine) in comparison to agents
      with lower affinity or non-selective serotonin reuptake inhibition (as with
      mirtazapine or doxepin). Comparison of group-specific aggregated data (SSRI vs.
      non-SSRI) revealed significant differences regarding the "protective effect" on
      the development of haemorrhages between groups SSRI vs. non-SSRI in favour of non
      SSRI in nearly all countries as well as in the total dataset. Our findings
      provide preliminary evidence that agents with increased affinity to the 5-HTT
      and/or selective serotonin reuptake inhibition may be associated with an
      increased risk of bleeding. 

PMID- 26208959
TI  - Amyloid-beta 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3
      AD trials.
AB  - OBJECTIVE: To evaluate the effects of bapineuzumab on brain beta-amyloid (Abeta)
      burden using (11)C-Pittsburgh compound B ((11)C-PiB)-PET. METHODS: Two phase 3
      clinical trials, 1 each in apolipoprotein APOE epsilon4 carriers and noncarriers,
      were conducted in patients with mild to moderate Alzheimer disease dementia.
      Bapineuzumab, an anti-Abeta monoclonal antibody, or placebo, was administered by
      IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain
      fibrillar Abeta over 71 weeks using an (11)C-PiB-PET standardized uptake value
      ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5
      cortical regions of interest with cerebellar gray matter as the reference region.
      RESULTS: A total of 115 carriers and 39 noncarriers were analyzed. The difference
      (delta) in mean baseline to 71 week change in (11)C-PiB-PET GCA between
      bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo delta
      = -0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5
      mg/kg vs placebo delta = -0.068; p = 0.027; 1.0 mg/kg vs placebo delta = -0.133;
      p = 0.028) but not in the noncarrier trial separately. Analyses by individual
      region of interest and in mild disease yielded findings similar to the main trial
      results. CONCLUSIONS: The (11)C-PiB-PET imaging results demonstrated reduction of
      fibrillar Abeta accumulation in patients with Alzheimer disease treated with
      bapineuzumab; however, as no clinical benefit was observed, the findings are
      consistent with the hypotheses that bapineuzumab may not have been initiated
      early enough in the disease course, the doses were insufficient, or the most
      critical Abeta species were inadequately targeted.

PMID- 26208983
TI  - Clinical profiles of stigma experiences, self-esteem and social relationships
      among people with schizophrenia, depressive, and bipolar disorders.
AB  - Some mental illnesses and certain mental health care environments can be severely
      stigmatizing, which seems to be related to decreased self-esteem and a
      deterioration of the quality of social relationships for people with mental
      illness. This study aims to identify clinical profiles characterized by clinical
      diagnoses more strongly associated with the treatment settings and related to
      internalized stigma, self-esteem and satisfaction with social relationships. It
      also aimed to analyze associations between clinical profiles and socio
      demographic indicators. Multiple correspondence analysis and cluster analysis
      were performed on a sample of 261 individuals with schizophrenia and mood
      disorders, from hospital-based and community-based facilities. MCA showed four
      distinct clinical profiles allowing a differentiation among levels of:
      internalized stigma, social relationship satisfaction and self-esteem. Overall,
      results revealed that internalized stigma remains a pervasive problem for some
      people with schizophrenia and mood disorders. Particularly, internalized stigma
      and social relationships dissatisfaction and associated socio-demographic
      indicators appear to be a risk factor for social isolation for individuals with
      schizophrenia, which may worsen the course of the disorder. Our findings
      highlight the importance to develop structured interventions aimed to reduce
      internalized stigma, and exclusion of those who suffer the loss of their social
      roles and networks. 

PMID- 26208984
TI  - Dietary patterns derived by reduced rank regression (RRR) and depressive symptoms
      in Japanese employees: The Furukawa nutrition and health study.
AB  - Depression has been linked to the overall diet using both exploratory and pre
      defined methods. However, neither of these methods incorporates specific
      knowledge on nutrient-disease associations. The aim of the present study was to
      empirically identify dietary patterns using reduced rank regression and to
      examine their relations to depressive symptoms. Participants were 2006 Japanese
      employees aged 19-69 years. Depressive symptoms were assessed using the Center
      for Epidemiologic Studies Depression Scale. Diet was assessed using a validated,
      self-administered diet history questionnaire. Dietary patterns were extracted by
      reduced rank regression with 6 depression-related nutrients as response
      variables. Logistic regression was used to estimate odds ratios of depressive
      symptoms adjusted for potential confounders. A dietary pattern characterized by a
      high intake of vegetables, mushrooms, seaweeds, soybean products, green tea,
      potatoes, fruits, and small fish with bones and a low intake of rice was
      associated with fewer depressive symptoms. The multivariable-adjusted odds ratios
      of having depressive symptoms were 0.62 (95% confidence interval, 0.48-0.81) in
      the highest versus lowest tertiles of dietary score. Results suggest that
      adherence to a diet rich in vegetables, fruits, and typical Japanese foods,
      including mushrooms, seaweeds, soybean products, and green tea, is associated
      with a lower probability of having depressive symptoms. 

PMID- 26208985
TI  - A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive
      treatment to risperidone: Effects on aberrant behavior in children with autism.
AB  - To assess the safety and efficacy of pioglitazone added to risperidone in the
      treatment of irritability in autistic disorder (AD), we conducted this study. In
      a 10-week, randomized, double-blind, parallel-group, placebo-controlled clinical
      trial, 44 outpatients of both genders aged 4-12 years with a diagnosis of AD and
      a score of >=12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability
      subscale were included. Mean change of ABC-C irritability subscale score as
      primary outcome, change in other ABC-C subscale scores and partial and complete
      responses were compared between two groups. Twenty patients completed the trial
      in each group. Level of reduction and effect of time*treatment interaction in the
      treatment group were significant for irritability (P=0.03), lethargy/social
      withdrawal (P=0.04) and hyperactivity/non-compliance (P=0.03) but not for
      stereotypic behavior and inappropriate speech subscales compared with the placebo
      group. Vomiting and headache were the most frequent reported side-effects.
      Results of this preliminary study indicate positive effects of pioglitazone
      compared with placebo in improving the behavioral symptoms of AD. 

PMID- 26208986
TI  - Increased IL-3 serum levels in chronic patients with schizophrenia: Associated
      with psychopathology.
AB  - Schizophrenia is associated with the inflammation-related pathways, including
      aberrant cytokines levels. In this study, we examined the association of serum IL
      3 levels with psychopahological symtoms in chronic schizophrenia. Serum IL-3
      levels were assessed in 42 patients diagnosed with schizophrenia and compared to
      43 healthy control subjects matched for age and gender. Schizophrenia
      symptomatology was assessed with the Positive and Negative Syndrome Scale
      (PANSS), and serum IL-3 levels were measured by sandwich enzyme-linked
      immunosorbent assay (ELISA). Our results showed that IL-3 levels were
      significantly increased in patients with chronic schizophrenia compared to
      healthy control subjects. Correlation analysis revealed a significant positive
      correlation between the IL-3 levels and the PANSS general subscore. Moreover, IL
      3 levels were significantly positively correlated with depressive subscore. Our
      results suggested that IL-3 related pathway is associated with psychopathology of
      schizophrenia patients. 

PMID- 26208987
TI  - Firearm ownership in veterans entering residential PTSD treatment: Associations
      with suicide ideation, attempts, and combat exposure.
AB  - This study aimed to describe the frequency of firearm ownership in veterans
      entering residential treatment for posttraumatic stress disorder (PTSD) and
      examine the association of firearm ownership with suicide ideation and suicide
      attempt history, combat exposure, and PTSD symptom severity. Two samples of
      veterans entering residential PTSD treatment were assessed at intake using self
      report measures. Approximately one third of participants endorsed firearm
      ownership across the two samples. Analyses with a sample predominantly comprised
      of Vietnam Veterans found that those who endorsed both suicide ideation and prior
      suicide attempts were less likely to own a firearm compared to suicide ideators
      and non-suicidal participants. In addition, more frequent combat exposure, but
      not PTSD symptom severity, was associated with firearm ownership in both samples
      and most participants endorsed using safe storage practices. These lower rates of
      firearm ownership generally, and in those with suicide ideation and prior
      attempts in particular, may reflect an increased focused on means restriction in
      treatment for combat-related PTSD. Means restriction counseling among PTSD
      treatment seeking veterans should target those with combat exposure. 

PMID- 26208988
TI  - Cascading and combined effects of cognitive deficits and residual symptoms on
      functional outcome in schizophrenia - A path-analytical approach.
AB  - Understanding the complex relationship among determinants of real-world
      functioning in schizophrenia patients in remission is important in planning
      recovery-oriented interventions. We explored two path-analytical models of
      functioning in schizophrenia. 170 Schizophrenia patients remitted from positive
      symptoms underwent fairly comprehensive assessments of cognition - neurocognition
      (NC) and social cognition (SC), residual symptoms - insight, motivation and other
      negative symptoms, and socio-occupational functioning. We explored (a) a
      cascading model, where NC predicted functional outcome through its effects on
      other determinants and (b) a combined model, incorporating additional direct
      paths from each of the determinants. The combined model, and not the cascading
      model demonstrated a good fit. Post-hoc trimming of the combined model by
      elimination of non-significant paths maintained the goodness-of-fit and was
      retained as the final model. In addition to the direct paths, this final model
      demonstrated that (a) NC influenced functioning through SC and insight and (b) SC
      influenced functioning through motivation and negative symptoms. This suggests
      that NC and SC may influence functional outcome directly, as well as indirectly,
      via specific impact on insight, and motivation and negative symptoms
      respectively. 

PMID- 26208989
TI  - Patients' subjective rating of mental health improvement in a randomised
      controlled trial.
AB  - We used UK CUtLASS RCT data to establish that patients' rating of mental health
      improvement (baseline to week 12) correlated significantly with percentage
      symptom improvement (PANSS). In a regression analysis predictors of the patient's
      week 12 mental health rating were percentage change in positive symptoms (PANSS),
      DAI score and the patient's rating of side effects. Patients in an RCT were able
      to subjectively rate their mental health status, validated by objective
      improvement on the PANSS. 

PMID- 26208990
TI  - Gene-expression analysis of a colorectal cancer-specific discriminatory
      transcript set on formalin-fixed, paraffin-embedded (FFPE) tissue samples.
AB  - BACKGROUND: A recently published transcript set is suitable for gene expression
      based discrimination of normal colonic and colorectal cancer (CRC) biopsy
      samples. Our aim was to test the discriminatory power of the CRC-specific
      transcript set on independent biopsies and on formalin-fixed, paraffin-embedded
      (FFPE) tissue samples. METHODS: Total RNA isolations were performed with the
      automated MagNA Pure 96 Cellular RNA Large Volume Kit (Roche) from fresh frozen
      biopsies stored in RNALater (CRC (n = 15) and healthy colonic (n = 15)),
      furthermore from FFPE specimens including CRC (n = 15) and normal adjacent tissue
      (NAT) (n = 15) specimens next to the tumor. After quality and quantity
      measurements, gene expression analysis of a colorectal cancer-specific marker set
      with 11 genes (CA7, COL12A1, CXCL1, CXCL2, CHI3L1, GREM1, IL1B, IL1RN, IL8, MMP3,
      SLC5A7) was performed with array real-time PCR using Transcriptor First Strand
      cDNA Synthesis Kit (Roche) and RealTime ready assays on LightCycler480 System
      (Roche). In situ hybridization for two selected transcripts (CA7, CXCL1) was
      performed on NAT (n = 3), adenoma (n = 3) and CRC (n = 3) FFPE samples. RESULTS:
      Although analytical parameters of automatically isolated RNA samples showed
      differences between fresh frozen biopsy and FFPE samples, both quantity and the
      quality enabled their application in gene expression analyses. CRC and normal
      fresh frozen biopsy samples could be distinguished with 93.3% sensitivity and
      86.7% specificity and FFPE samples with 96.7 and 70.0%, respectively. In situ
      hybridization could confirm the upregulation of CXCL1 and downregulation of CA7
      in colorectal adenomas and tumors compared to healthy controls. CONCLUSION:
      According to our results, gene expression analysis of the analyzed colorectal
      cancer-specific marker set can also be performed from FFPE tissue material. With
      the addition of an automated workflow, this marker set may enhance the objective
      classification of colorectal neoplasias in the routine procedure in the future.

PMID- 26208991
TI  - Comparison of clinically suspected injuries with injuries detected at whole-body
      CT in suspected multi-trauma victims.
AB  - AIM: To assess the accuracy of the trauma team leader's clinical suspicion of
      injury in patients who have undergone whole-body computed tomography (WBCT) for
      suspected polytrauma, and to assess the frequency of unsuspected injuries and
      specific patterns of injury at WBCT. MATERIALS AND METHODS: Requests for patients
      who underwent WBCT for suspected polytrauma from April 2011 to March 2014 were
      reviewed and each body area that was clinically suspected to be injured was
      recorded. Body areas were divided into the following groups based on anatomical
      regions covered in each segment of the WBCT examination: head (including facial
      bones); neck (including cervical spine); chest (including thoracic spine); and
      abdomen/pelvis (including lumbar spine). The formal radiology report for each
      study was reviewed and injuries found at CT were grouped into the same body
      areas. For each patient, the number of clinically suspected injured areas was
      compared to the number of confirmed injured areas at WBCT. RESULTS: Five hundred
      and eighty-eight patients were included in the study. Thirty-two percent
      (186/588) had a normal scan. Ninety-three percent (546/588) had fewer injured
      body areas at WBCT than suspected. Four percent (27/588) had the equivalent
      number of injured areas at WBCT as suspected. Three percent (15/588) had more
      injured areas at WBCT than suspected. Fifty percent (263/527) with clinically
      suspected chest injuries were confirmed to have chest injuries at WBCT. This was
      lower for other areas: abdomen/pelvis 31% (165/535); head 29% (155/533); neck 13%
      (66/513). Four percent of (24/588) patients had unsuspected injuries found at
      WBCT. Seventy-five percent (18/24) of unsuspected injuries were considered as
      serious, where failure to treat would have the potential for significant
      morbidity. Most of these patients had severe injuries to other body areas that
      were correctly suspected. Of the 165 with abdominal/pelvic region injuries, there
      were associated injuries in the thoracic region in 62% (103/165) cases. Of the
      278 thoracic injuries, there were abdominal/pelvic region injuries in 37%
      (103/278) and injuries to the neck in 19% (52/278) cases. Of the 158 head
      injuries, there were neck injuries in 22% (34/158) cases. CONCLUSION: Clinical
      suspicion of injury correlates poorly with findings at WBCT, with a high
      proportion of uninjured body areas. The number of unsuspected injuries found at
      WBCT was low, but the majority of these were serious injuries, possibly masked by
      distracting injury to other body areas. The use of a WBCT protocol is recommended
      for suspected polytrauma, but regular monitoring of WBCT findings and regular
      feedback of the results to emergency physicians is suggested to help inform their
      selection of patients for trauma WBCT.

PMID- 26208992
TI  - Whole-body diffusion-weighted MRI and (18)F-FDG PET/CT can discriminate between
      different lymphoma subtypes.
AB  - AIM: To determine whether combined 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG)
      positron-emission tomography (PET)/computed tomography (CT) and diffusion
      weighted imaging (DWI) can be used for characterisation of different lymphoma
      subtypes, i.e., indolent versus aggressive lymphoma, and also to assess the
      prognostic value of different quantitative parameters of whole-body (WB) DWI and
      (18)F-FDG PET/CT. MATERIALS AND METHODS: Pre-therapeutic WB magnetic resonance
      imaging (MRI) including DWI and (18)F-FDG PET/CT were performed in lymphoma
      patients. Different quantitative DWI and (18)F-FDG PET/CT parameters were
      evaluated for characterisation of different lymphoma subtypes. These parameters
      were also correlated, both separately and in combination, against overall
      survival (OS) and progression-free survival (PFS). A lesion-by-lesion analysis
      was performed for correlation analysis between maximum standardised uptake value
      (SUVmax), mean standardised uptake value (SUVmean) and mean apparent diffusion
      coefficient (ADC). RESULTS: Fifty patients were included in the study and divided
      into three groups: Hodgkin's lymphoma (HL), n=12; aggressive non-Hodgkin's
      lymphoma (NHL), n=29 (including 20 patients with diffuse large B-cell lymphoma,
      DLBCL); and indolent NHL, n=9. Indolent NHL showed significantly lower mean ADC
      values than the other two lymphoma groups (p=0.013). Aggressive NHL had a higher
      SUVmax than HL. The OS analysis of all patients showed a relationship (p=0.006)
      between increased mean ADC and longer OS. A model with both SUVmean and mean ADC,
      strengthened the possibility to predict PFS; however, a separate analysis of the
      DLBCL patients showed that none of the quantitative parameters could predict OS
      or PFS. CONCLUSION: ADC can discriminate between indolent and aggressive NHL.
      This finding can be useful in assessing possible transformation from indolent to
      aggressive NHL. ADC, ADC/SUV, and SUV cannot predict OS/PFS independent of
      lymphoma subtype.

PMID- 26208993
TI  - Cardiovascular disease in patients with COPD.

PMID- 26208995
TI  - Social network analysis of Pseudomonas aeruginosa in cystic fibrosis.

PMID- 26208994
TI  - The social network of cystic fibrosis centre care and shared Pseudomonas
      aeruginosa strain infection: a cross-sectional analysis.
AB  - BACKGROUND: Person-to-person transmission is a potential pathway of Pseudomonas
      aeruginosa acquisition in cystic fibrosis. Reports of cross-infection of shared
      cystic-fibrosis-specific P. aeruginosa strains across large geographical
      distances are concerning. Therefore, we aimed to assess the extent to which
      patient movement between cystic fibrosis centres contributes to dissemination.
      METHODS: We did a cross-sectional study to assess movement of patients with
      cystic fibrosis who were infected with P. aeruginosa between Sept 3, 2007, and
      June 16, 2010, at 18 Australian cystic fibrosis centres. We applied social
      network analysis to patient movement data from P. aeruginosa-infected patients to
      assess the role of patient mobility in P. aeruginosa genotype prevalence. We
      generated networks linking treatment centres based on the movement of patients
      attending adult and paediatric cystic fibrosis centres, and compared these with
      the movement of patients infected with all P. aeruginosa strains, unique strains,
      and predominant Australian shared strains (AUST-01 and AUST-02). We summarised
      connectivity using degree centrality, in-degree centrality, out-degree
      centrality, and k-core estimates. Infection control and surveillance practices
      were also assessed by use of a questionnaire. FINDINGS: 983 patients (mean age 25
      years [SD 10]; 551 [56%] male) provided 2887 P. aeruginosa isolates for ERIC-PCR
      genotyping, which yielded 531 distinct genotypes: 493 unique strains in 373
      patients and 38 shared strains in 610 patients. AUST-01 infections were
      associated with higher in-degree centrality (p=0.004) and k-core (p=0.005)
      estimates and AUST-02 infections with higher degree centrality (p=0.002), out
      degree centrality (p=0.002), and k-core (p=0.007) estimates for the previous
      health-care facilities; associations for the present cystic fibrosis centre were
      not significant. These findings were significant for adult patients (AUST-01 in
      degree centrality p=0.004 and k-core p=0.005; AUST-02 degree centrality p=0.004,
      out-degree centrality p=0.003, and k-core p=0.007), but not for paediatric
      patients. By contrast, infections with unique strains were associated with a
      lower k-core estimate for the present cystic fibrosis centre overall (p<0.0001);
      this finding was significant in adults (p<0.0001), but not in paediatric
      patients. INTERPRETATION: Our results show that the connectivity of cystic
      fibrosis centres, as measured by the movement of patients, seems to be an
      important risk factor for the acquisition of shared P. aeruginosa strain
      infections. These results show the importance of prioritising infection control
      interventions (eg, prospective molecular surveillance for shared P. aeruginosa
      strains, strict universal infection control precautions, and hospital design and
      ventilation) to limit P. aeruginosa cross-infection between patients with cystic
      fibrosis. FUNDING: Australian National Health and Medical Research Council;
      Children's Health Foundation Queensland; Office of Health and Medical Research,
      Queensland Health; European Respiratory Society-European Union; Australian Cystic
      Fibrosis Research Trust; Prince Charles Hospital Foundation; and Rotary
      Australia.

PMID- 26208996
TI  - Burden of tuberculosis in intensive care units in Cape Town, South Africa, and
      assessment of the accuracy and effect on patient outcomes of the Xpert MTB/RIF
      test on tracheal aspirate samples for diagnosis of pulmonary tuberculosis: a
      prospective burden of disease study with a nested randomised controlled trial.
AB  - BACKGROUND: There are few prospective data about the incidence and mortality
      associated with pulmonary tuberculosis in intensive care units (ICUs), and none
      on the accuracy and clinical effect of the Xpert-MTB/RIF assay in this setting.
      We aimed to measure the frequency of culture-positive tuberculosis in ICUs in
      Cape Town, South Africa and to assess the performance and effect on patient
      outcomes of Xpert MTB/RIF versus smear microscopy for diagnosis of tuberculosis.
      METHODS: We did a prospective burden of disease study with a randomised
      controlled substudy at the ICUs of four hospitals in Cape Town. Mechanically
      ventilated adults (>=18 years) with suspected pulmonary tuberculosis admitted
      between Aug 1, 2010, and July 31, 2013 (irrespective of the reason for
      admission), were prospectively investigated by culture, and by Xpert-MTB/RIF
      testing or smear microscopy, of tracheal aspirate samples. In the substudy,
      patients were randomly assigned (1:1), via a computer-generated allocation list,
      to smear microscopy or Xpert MTB/RIF. Participants, caregivers, and outcome
      assessors were not masked to group assignment. Only the laboratory staff were
      blinded to the clinical details of the participants. In November, 2012, Xpert
      MTB/RIF was adopted as the initial diagnostic test for respiratory samples in
      Western Cape province. Thereafter, patients received Xpert MTB/MIF and culture as
      standard of care. For the whole study cohort, the primary outcome was the
      frequency of bacteriologically confirmed tuberculosis. The primary endpoint of
      the randomised substudy was the proportion of culture-positive patients on
      treatment at 48 h after enrolment. The randomised substudy is registered with
      ClinicalTrials.gov, number NCT01530568. FINDINGS: We investigated 341 patients
      for suspected pulmonary tuberculosis out of a total of 2309 ICU admissions. 46
      (15%) of 317 patients included in the final analysis had a positive test for
      tuberculosis (Xpert MTB/RIF or culture). Culture-positive patients who failed to
      initiate treatment (adjusted HR 4.49, 95% CI 1.45-13.89) or who received
      inotropes (4.33, 1.49-12.60) were more likely to die. However, tuberculosis
      status was not associated with 28-day or 90-day mortality. In the substudy, we
      randomly assigned 115 patients to smear microscopy and 111 to Xpert MTB/RIF.
      Smear microscopy detected six (43%) of 14 culture-positive patients, and Xpert
      MTB/RIF detected 11 (100%) of 11 culture-positive patients (p=0.002). The
      proportion of culture-positive patients on treatment at 48 h was higher in the
      Xpert MTB/RIF group than in the smear microscopy group (11 [92%] of 12 vs nine
      [53%] of 17; p=0.043), although use of Xpert MTB/RIF had no effect on mortality
      or other patient outcomes. INTERPRETATION: Tuberculosis is fairly common in ICUs
      in high-burden settings, and clinicians should screen and test patients for
      tuberculosis with Xpert MTB/RIF where available. This test improves diagnostic
      yield and rates of treatment initiation, and reduces unnecessary treatment, but
      might not increase the total number of patients on treatment when empirical
      treatment is widely used. A suspected diagnosis of pulmonary tuberculosis should
      not exclude patients from ICU care in resource-limited settings because mortality
      is unaffected by the presence of this disease. FUNDING: European and Developing
      Countries Clinical Trials Partnership, South African Medical Research Council,
      and the Discovery Foundation.

PMID- 26208997
TI  - Should countries implement Xpert MTB/RIF when empirical treatment precludes a
      clinical effect?

PMID- 26208998
TI  - Risk of cardiovascular comorbidity in patients with chronic obstructive pulmonary
      disease: a systematic review and meta-analysis.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a systemic
      inflammatory disorder associated with increased comorbid prevalence of
      cardiovascular diseases. We aimed to quantify the magnitudes of association
      between overall and specific types of cardiovascular disease, major
      cardiovascular risk factors, and COPD. METHODS: We searched Cochrane, Medline,
      and Embase databases for studies published between Jan 1, 1980, and April 30,
      2015, on the prevalence of cardiovascular disease and its risk factors in
      patients with COPD versus matched controls or random samples from the general
      public. We assessed associations with random-effects meta-analyses. We studied
      heterogeneity and biases with random-effects meta-regressions, jackknife
      sensitivity analyses, assessment of funnel plots, and Egger tests. FINDINGS: We
      identified 18,176 unique references and included 29 datasets in the meta
      analyses. Compared with the non-COPD population, patients with COPD were more
      likely to be diagnosed with cardiovascular disease (odds ratio [OR] 2.46; 95% CI
      2.02-3.00; p<0.0001), including a two to five times higher risk of ischaemic
      heart disease, cardiac dysrhythmia, heart failure, diseases of the pulmonary
      circulation, and diseases of the arteries. Additionally, patients with COPD
      reported hypertension more often (OR 1.33, 95% CI 1.13-1.56; p=0.0007), diabetes
      (1.36, 1.21-1.53; p<0.0001], and ever smoking (4.25, 3.23-5.60; p<0.0001). The
      associations between COPD and these cardiovascular disease types and
      cardiovascular disease risk factors were consistent and valid across studies.
      Enrolment period, age, quality of data, and COPD diagnosis partly explained the
      heterogeneity. INTERPRETATION: The coexistence of COPD, cardiovascular disease,
      and major risk factors for cardiovascular disease highlights the crucial need for
      the development of strategies to screen for and reduce cardiovascular risks
      associated with COPD. FUNDING: Canadian Institutes of Health Research.

PMID- 26208999
TI  - A new phase of CFTR treatment for cystic fibrosis?

PMID- 26209000
TI  - Angiotensin receptor neprilysin inhibition in heart failure: mechanistic action
      and clinical impact.
AB  - Heart failure (HF) is an increasingly common syndrome associated with high
      mortality and economic burden, and there has been a paucity over the past decade
      of new pharmacotherapies that improve outcomes. However, recent data from a large
      randomized controlled trial compared the novel agent LCZ696, a dual-acting
      angiotensin receptor blocker and neprilysin inhibitor (ARNi), with the well
      established angiotensin-converting enzyme (ACE) inhibitor enalapril and found
      significant reduction in mortality among the chronic reduced ejection fraction HF
      population. Preclinical and clinical data suggest that neprilysin inhibition
      provides beneficial outcomes in HF patients by preventing the degradation of
      natriuretic peptides and thereby promoting natriuresis and vasodilatation and
      counteracting the negative cardiorenal effects of the up-regulated renin
      angiotensin-aldosterone system. Agents such as omapatrilat combined neprilysin
      and ACE inhibition but had increased rates of angioedema. Goals of an improved
      safety profile provided the rationale for the development of the ARNi LCZ696.
      Along with significant reductions in mortality and hospitalizations, clinical
      trials suggest that LCZ696 may improve surrogate markers of HF severity. In this
      paper, we review the preclinical and clinical data that led to the development of
      LCZ696, the understanding of the underlying mechanistic action, and the robust
      clinical impact that LCZ696 may have in the near future. 

PMID- 26209001
TI  - Triheptanoin Alleviates Ventricular Hypertrophy and Improves Myocardial Glucose
      Oxidation in Rats With Pressure Overload.
AB  - OBJECTIVE: Cardiac hypertrophy is characterized by changes in substrate
      utilization and activity of the Krebs cycle. We assessed the effects of
      triheptanoin, an odd-chain fat that might support the Krebs cycle, on cardiac
      metabolism and function in a model of cardiac hypertrophy. METHODS AND RESULTS:
      Rats were subjected to aortic banding (AoB) to induce pressure overload (PO).
      Starting at 1 week after AoB, rats were blindly fed a control diet or a special
      diet containing triheptanoin at 7% (T7 group) or 30% (T30 group) of total energy
      value. Six weeks after AoB, echocardiography revealed attenuated hypertrophy and
      improved diastolic function of the left ventricle. Isolated working heart
      perfusion showed similar cardiac power, fatty acid oxidation, substrate
      preference, and insulin response among groups. However, cardiac glucose oxidation
      (GO) was increased in the T30 group compared with the T7 and control groups.
      Blood levels of the odd-chain ketone body beta-hydroxypentanoate confirmed
      adequate bioavailability of triheptanoin. Importantly, they were directly
      proportional to cardiac GO. CONCLUSIONS: Treatment with triheptanoin-enriched
      diet reduces ventricular hypertrophy and improves diastolic function in rats with
      PO, which is associated with enhanced cardiac GO. The results suggest targeting
      supplementation of the Krebs cycle to approach ventricular and metabolic
      remodeling in cardiac hypertrophy.

PMID- 26209002
TI  - Validation of the Readmission Risk Score in Heart Failure Patients at a Tertiary
      Hospital.
AB  - BACKGROUND: The Readmission Risk score (RR score) is a software application
      developed to identify patients at increased risk for readmission. This score was
      developed to improve on the methodology for 30-day risk-standardized all-cause
      readmission rates (RSRRs) used by the Centers for Medicare and Medicaid Services
      for its quality reporting system. However, the utility of the RR score in
      clinical practice has not been independently validated. METHODS AND RESULTS: We
      included patients admitted with the primary discharge diagnosis of congestive
      heart failure (CHF) from September 2011 to August 2013. Data on individual
      components of the RR score were obtained by means of detailed chart review. We
      calculated the RR score of all admissions and examined its ability to predict 30
      day all-cause readmission. We repeated the analysis by randomly selecting 1
      admission per patient and also by including only those >= 65 years old. A total
      of 1,046 admissions met the inclusion criteria. Of these, 369 (35.28%) were
      readmitted within 30 days of discharge. The performance of the RR score was poor,
      with an area under the receiver operating characteristic curve (AUC) of 0.61 (95%
      confidence interval [CI] 0.57-0.64) for all age groups and 0.59 (95% CI 0.53
      0.64) for patients aged >= 65 years. The AUC for the RR score was 0.58 (95% CI
      0.50-0.65) in a randomly selected patient-level model. However, patients in the
      highest quartile of RR score were twice as likely to be readmitted as those in
      the lowest quartile (47.24% vs 24.69%; P < .001). The sensitivity and specificity
      of the RR score in predicting all cause readmissions were poor. CONCLUSION: Based
      on our single-institution data, patients with CHF readmitted within 30 days had a
      higher RR score than those not readmitted. The ability of the RR score to predict
      future all-cause readmission was modest at best.

PMID- 26209003
TI  - Diuretic Response: Clinical and Hemodynamic Predictors and Relation to Clinical
      Outcome.
AB  - OBJECTIVE: The aims of this work were to investigate the clinical and hemodynamic
      profile underlying the response to loop diuretics in acute decompensated heart
      failure (ADHF), and to compare the relative usefulness of measures of diuretic
      resistance for predicting mortality. METHODS AND RESULTS: We studied 475 patients
      with ADHF, of whom 241 underwent right heart catheterization. Linear regression
      models were used to identify factors that affected urine output. Loop diuretics
      response was estimated as (1) net fluid loss per 40 mg furosemide equivalents and
      (2) urine output produced per 40 mg furosemide equivalents. In a multivariable
      regression model, key independent predictors of urine output included diuretic
      dose (partial r = 0.44), baseline renal function (partial r = 0.38), systolic
      blood pressure (partial r = 0.26), and fluid intake (partial r = 0.31; all P <
      .0001). Among hemodynamic variables, elevated right atrial pressure was
      associated with greater urine output (partial r = 0.19; P = .002). The partial
      correlation attributable to diuretic dose (partial R2 = 0.19) accounted for
      approximately one-half of the variance in urine output explained by the model
      (model R2 = 0.40).Cox regression models demonstrated inverse relationships
      between quartiles of net fluid loss (P = .004) and quartiles of urine output (P =
      .04) per 40 mg furosemide and 6-month mortality. When comparing nested models,
      the model based on net fluid loss was better than the model based on urine output
      for the prediction of mortality (chi2 = 8.1; 3 df; P = .04). CONCLUSIONS: In
      patients with ADHF, beyond diuretic dose, other parameters including renal
      function, hemodynamic status, the degree of volume overload, and fluids intake
      also affect urine output. Measures of loop diuretic response are associated with
      short-term mortality.

PMID- 26209004
TI  - Intensification of Medication Therapy for Cardiorenal Syndrome in Acute
      Decompensated Heart Failure.
AB  - BACKGROUND: Worsening renal function in heart failure may be related to increased
      venous congestion, decreased cardiac output, or both. Diuretics are universally
      used in acute decompensated heart failure, but they may be ineffective and may
      lead to azotemia. We aimed to compare the decongestive properties of a urine
      output-guided diuretic adjustment and standard therapy for the management of
      cardiorenal syndrome in acute decompensated heart failure. METHODS AND RESULTS:
      Data were pooled from subjects randomized to the stepwise pharmacologic care
      algorithm (SPCA) in the CARRESS-HF trial and those who developed cardiorenal
      syndrome (rise in creatinine >0.3 mg/dL) in the DOSE-AHF and ROSE-AHF trials.
      Patients treated with SPCA (n = 94) were compared with patients treated with
      standard decongestive therapy (SDT) that included intravenous loop diuretic use
      (DOSE-AHF and ROSE-AHF; n = 107) at the time of cardiorenal syndrome and followed
      for net fluid balance, weight loss, and changing renal function. The SPCA group
      had higher degrees of jugular venous pressure (P < .0001) at the time of
      cardiorenal syndrome. The group that received SPCA had more weight change (-3.4
      +/- 5.2 lb) and more net fluid loss (1.705 +/- 1.417 L) after 24 hours than the
      SDT group (-0.8 +/- 3.4 lb and 0.892 +/- 1.395 L, respectively; P < .001 for
      both) with a slight improvement in renal function (creatinine change -0.1 +/- 0.3
      vs 0.0 +/- 0.3 mg/dL, respectively; P = .03). CONCLUSIONS: Compared with SDT,
      patients who received an intensification of medication therapy for treating
      persisting congestion had greater net fluid and weight loss without being
      associated with renal compromise.

PMID- 26209005
TI  - Determinations for Pesticides on Black, Green, Oolong, and White Teas by Gas
      Chromatography Triple-Quadrupole Mass Spectrometry.
AB  - Black, green, white, and Oolong teas, all derived from leaves of Camellia
      sinensis, are widely consumed throughout the world and represent a significant
      part of the beverages consumed by Americans. A gas chromatography-triple
      quadrupole-based method, previously validated for pesticides on dried botanical
      dietary supplements, including green tea, was used to measure pesticides
      fortified into black and green teas at 10, 25, 100, and 500 MUg/kg. Teas from 18
      vendors of tea products were then surveyed for pesticides. Of 62 black, green,
      white, and Oolong tea products, 31 (50%) had residues of pesticides for which no
      United States Environmental Protection Agency tolerances are established for tea.
      The following pesticides were identified on tea leaves, with concentrations
      between 1 and 3200 MUg/kg: anthraquinone, azoxystrobin, bifenthrin, buprofesin,
      chlorpyrifos, cyhalothrin, cypermethrin, DDE-p,p', DDT-o,p, DDT-p,p',
      deltamethrin, endosulfan, fenvalerate, heptachlor, hexachlorocyclohexanes
      (alpha,beta,gamma,delta), phenylphenol, pyridaben, tebuconazole, tebufenpyrad,
      and triazophos. DDT-p,p' was found at much higher concentrations than DDE-p,p' or
      DDT-o,p' in 9 of 10 teas with DDTs. A comparison between three commercially
      available solid-phase extraction (SPE) column brands of the same type revealed
      that two brands of SPE columns could be interchanged without modification of the
      tea method. 

PMID- 26209006
TI  - Associations of lipid levels susceptibility loci with coronary artery disease in
      Chinese population.
AB  - BACKGROUND: Recent genome-wide association studies (GWAS) have identified several
      single nucleotide polymorphisms (SNPs) that were associated with blood lipid
      levels in Caucasians. This study investigated whether these loci influenced lipid
      levels and whether they were associated with the risk of coronary artery disease
      (CAD) and its angiographic severity in Chinese population. METHODS: Six SNPs were
      genotyped in 1100 CAD cases and 1069 controls using the high-resolution melting
      (HRM) method. Coronary atherosclerosis severity was assessed by the vessel scores
      and the Gensini scoring system. RESULTS: Among the 6 SNPs and the genetic risks
      scores (GRS), the minor alleles of HNF1A rs1169288 (odd ratio (OR) = 1.18, 95%
      confidence interval (CI) 1.05-1.33, P = 0.006) and MADD-FOLH1 rs7395662 (OR =
      1.20, 95% CI 1.07-1.36, P = 0.002) as well as the GRS (P = 1.06 * 10(-5)) were
      significantly associated with increased risk of CAD after false discovery rate
      (FDR) correction. The vessel (P = 0.013) and Gensini scores (beta = 0.113, P =
      0.002) differed among CAD patients with different SNP rs1169288 C > T genotypes.
      The multiple linear regression analyses using an additive model revealed that the
      minor allele C of SNP rs1169288 (beta = 0.060, P = 0.001) and the GRS (beta =
      0.033, P = 3.59 * 10(-4)) were significantly associated with increased total
      cholesterol (TC) levels, the minor allele A of SNP rs7395662 (beta = -0.024, P =
      0.007) and the GRS (beta = -0.013, P = 0.004) were significantly associated with
      decreased high-density lipoprotein cholesterol (HDL-c) levels. CONCLUSIONS: The
      present study demonstrated that SNPs rs1169288, rs7395662 and the GRS were
      significantly associated with lipid levels and the risk of CAD in Chinese
      population. Furthermore, the allele C of SNP rs1169288 increased the odds of
      coronary atherosclerosis severity.

PMID- 26209007
TI  - Agile text mining for the 2014 i2b2/UTHealth Cardiac risk factors challenge.
AB  - This paper describes the use of an agile text mining platform (Linguamatics'
      Interactive Information Extraction Platform, I2E) to extract document-level
      cardiac risk factors in patient records as defined in the i2b2/UTHealth 2014
      challenge. The approach uses a data-driven rule-based methodology with the
      addition of a simple supervised classifier. We demonstrate that agile text mining
      allows for rapid optimization of extraction strategies, while post-processing can
      leverage annotation guidelines, corpus statistics and logic inferred from the
      gold standard data. We also show how data imbalance in a training set affects
      performance. Evaluation of this approach on the test data gave an F-Score of
      91.7%, one percent behind the top performing system. 

PMID- 26209008
TI  - The optimal minimally invasive percutaneous nephrolithotomy strategy for the
      treatment of staghorn stones in a solitary kidney.
AB  - The objective of the study was to analyze the treatment outcomes for staghorn
      stones in patients with solitary kidney using either the single-tract or the
      multi-tract minimally invasive percutaneous nephrolithotomy (MPCNL). We
      retrospectively reviewed 105 patients who underwent MPCNL for staghorn calculi in
      solitary kidney from 2012 to 2014. The patients who underwent the single-tract
      approach (71 patients) were assigned to Group 1. The 34 patients who underwent
      the multi-tract approach (34 patients) were assigned to Group 2. We recorded and
      compared the patient's demographics, intraoperative parameters, and post
      operative outcomes. We also analyzed any complications as a result of the
      particular procedure, as well as any resulting stone-free rates (SFRs). The mean
      number of access tracts was 2.38 +/- 0.70 (range 2-4) for Group 2. The mean
      operative time was longer for Group 2, p = 0.01. The initial SFR was 52.1% for
      Group 1 and 47.1% for Group 2 after the one-session procedure, p = 0.63.The final
      SFR improved to 83.1 and 79.4% for both groups following auxiliary treatment, p =
      0.65. The mean hemoglobin drop was higher in Group 2 as compared to Group 1, p <
      0.01. There was no significant difference in the change of mean serum creatinine
      in either group. There were fewer overall complications in Group 1 than in Group
      2 (23.9 vs. 44.1%). Almost half of the patients who underwent multi-tract MPCNL
      required an additional procedure to achieve satisfactory stone clearance. The
      results showed that single-tract MPCNL might be a better treatment option for
      staghorn stones in a solitary kidney with the same therapeutic outcome, but with
      less complications.

PMID- 26209009
TI  - Shared decision making: why do patients choose ureteroscopy?
AB  - To evaluate patient's characteristics that affects their decision on the
      management of asymptomatic renal calculi, and to determine the impact of
      anesthetic on the selection of shockwave lithotripsy (SWL). A survey was
      distributed to 100 patients in our multi-disciplinary stone clinic. The patients
      were given a hypothetical scenario of an asymptomatic 8 mm lower pole stone and
      descriptions for managements options including active surveillance (annual
      radiography, 40% chance of growth >10 mm within 4 years, 20% chance of passage),
      SWL under conscious sedation (65% success rate), and URS (90% success rate, with
      stent placement for 1 week). Patients were asked what was the most important
      variable impacting the choice of treatment. Patients preferred SWL (45%) over URS
      (32%) and active surveillance (23%). Patients with a previous experience with URS
      were more likely to choose it again (p = 0.0433). Decisions were driven primarily
      by success rate (52%), followed by risk of complications (29%), postoperative
      pain (7%) and others (12%). Patients choosing URS had the highest magnitude of
      history of pain (p = 0.03) and were more likely to prioritize success (78%) and
      less likely to prioritize surgical risk (13%) or anticipated pain after surgery
      (0%) (p = 0.01). Most (85%) of the patients would rely on the physician's
      recommendation for the treatment modality. Patients place differing value on risk
      versus success. As they rely heavily on the physician's recommendation, it is
      important that their urologist determine whether risk or success is of highest
      priority for them to facilitate a shared medical decision.

PMID- 26209010
TI  - Micro-percutaneous nephrolithotomy in infants: a single-center experience.
AB  - This study aimed to investigate the effectiveness and reliability of micro
      percutaneous nephrolithotomy (micro-PNL) for the management of kidney stones in
      pediatric patients. This retrospective study included 24 infants that underwent
      micro-PNL for renal stones between March 2012 and April 2015. The inclusion
      criteria included: age younger than 2 years, stone size <20 mm, absence of
      urinary tract malformations and active infection, and no coagulopathy. Stone-free
      rates were assessed one month postoperatively by ultrasonography (USG) and
      kidneys, ureters, bladder (KUB) radiography. Complications were classified
      according to the Clavien classification system. The mean age of the patients was
      15.8 +/- 7.8 months (range, 8-23) and the mean stone size was 13.5 +/- 3.84 mm.
      Intra-renal access was achieved using USG in 11 patients and KUB fluoroscopy in
      13 patients. The operation time and fluoroscopic screening time were 53.7 +/-
      10.35 and 1.4 +/- 0.9 min, respectively. The mean hospital stay was 2.5 +/- 0.8
      days, and the mean drop in the hemoglobin level was 0.51 +/- 0.34 g/dL. Bleeding
      requiring blood transfusion was not observed. A ureteral J stent was implanted
      perioperatively in four patients because of stone burden. Four patients
      complained of postoperative renal colic (Clavien grade 1) and postoperative fever
      was observed in two patients. Definitive success rates were as follows: the stone
      free rate was 83.3% (n = 20) and residual fragments were observed in four
      patients.

PMID- 26209011
TI  - Post-transcriptional regulation of cardiac sodium channel gene SCN5A expression
      and function by miR-192-5p.
AB  - The SCN5A gene encodes cardiac sodium channel Nav1.5 and causes lethal
      ventricular arrhythmias/sudden death and atrial fibrillation (AF) when mutated.
      MicroRNAs (miRNAs) are important post-transcriptional regulators of gene
      expression, and involved in the pathogenesis of many diseases. However, little is
      known about the regulation of SCN5A by miRNAs. Here we reveal a novel post
      transcriptional regulatory mechanism for expression and function of SCN5A/Nav1.5
      via miR-192-5p. Bioinformatic analysis revealed that the 3'-UTR of human and
      rhesus SCN5A, but not elephant, pig, rabbit, mouse, and rat SCN5A, contained a
      target binding site for miR-192-5p and dual luciferase reporter assays showed
      that the site was critical for down-regulation of human SCN5A. With Western blot
      assays and electrophysiological studies, we demonstrated that miR-192-5p
      significantly reduced expression of SCN5A and Nav1.5 as well as peak sodium
      current density INa generated by Nav1.5. Notably, in situ hybridization,
      immunohistochemistry and real-time qPCR analyses showed that miR-192-5p was up
      regulated in tissue samples from AF patients, which was associated with down
      regulation of SCN5A/Nav1.5. These results demonstrate an important post
      transcriptional role of miR-192-5p in post-transcriptional regulation of Nav1.5,
      reveal a novel role of miR-192-5p in cardiac physiology and disease, and provide
      a new target for novel miRNA-based antiarrhythmic therapy for diseases with
      reduced INa. 

PMID- 26209012
TI  - Decrease in APP and CP mRNA expression supports impairment of iron export in
      Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder of still unknown
      etiology and the leading cause of dementia worldwide. Besides its main
      neuropathological hallmarks, a dysfunctional homeostasis of transition metals has
      been reported to play a pivotal role in the pathogenesis of this disease.
      Dysregulation of iron (Fe) metabolism in AD has been suggested, particularly at
      the level of cellular iron efflux. Herein, we intended to further clarify the
      molecular mechanisms underlying Fe homeostasis in AD. In order to achieve this
      goal, the expression of specific Fe metabolism-related genes directly involved in
      Fe regulation and export was assessed in peripheral blood mononuclear cells
      (PBMCs) from 73AD patients and 74 controls by quantitative PCR. The results
      obtained showed a significant decrease in the expression of aconitase 1 (ACO1;
      P=0.007); ceruloplasmin (CP; P<0.001) and amyloid-beta precursor protein (APP;
      P=0.006) genes in AD patients compared with healthy volunteers. These
      observations point out to a significant downregulation in the expression of genes
      associated with ferroportin-mediated cellular Fe export in PBMCs from AD
      patients, when compared to controls. Taken together, these findings support
      previous studies suggesting impairment of Fe homeostasis in AD, which may lead to
      cellular Fe retention and oxidative stress, a typical feature of this disease. 

PMID- 26209013
TI  - Cardiomyocyte-fibroblast interaction contributes to diabetic cardiomyopathy in
      mice: Role of HMGB1/TLR4/IL-33 axis.
AB  - Diabetic cardiomyopathy (DiCM) is characterized by myocardial fibrosis and
      dysfunction. In rodent models of diabetes myocardial HMGB1 increases while IL-33
      decreases. The major cardiac cell type expressing HMGB1 is the myocyte while the
      primary IL-33 expressing cell is the fibroblast. The aim of this study was to
      delineate the extracellular communication pathway(s) between cardiomyocytes and
      fibroblasts that contributes to murine DiCM. The streptozotocin (STZ)-induced
      murine model of diabetes and a cardiomyocyte/fibroblast co-culture challenged
      with high glucose were used. In STZ mice, myocardial HMGB1 expression was
      increased while IL-33 expression decreased (immunofluorescence and Western blot).
      In addition, STZ mice had an increased myocardial collagen deposition and
      myocardial dysfunction (pressure-volume loop analysis). An HMGB1 inhibitor (A
      box) or exogenous IL-33 prevented the myocardial collagen deposition and
      dysfunction. In the cardiomyocyte/fibroblast co-culture model, HG increased
      cardiomyocyte HMGB1 secretion, decreased fibroblast IL-33 expression, and
      increased fibroblast collagen I production. Further, using A-box and HMGB1 shRNA
      transfected myocytes, we found that cardiomyocyte-derived HMGB1 dramatically
      potentiated the HG-induced down-regulation of IL-33 and the increase in collagen
      I expression in the fibroblasts. The potentiating effects of the cardiomyocytes
      was diminished when toll-like receptor 4 deficient (TLR4(-/-)) fibroblasts were
      co-cultured with wild-type myocytes. Finally, TLR4(-/-) mice with diabetes had
      increased myocardial expression of HMGB1, but failed to down-regulate IL-33. The
      diabetes-induced myocardial collagen deposition and cardiac dysfunction were
      significantly attenuated in TLR4(-/-) mice. In conclusion, our findings support a
      role for "cardiomyocyte HMGB1-fibroblast TLR4/IL-33 axis" in the development of
      myocardial fibrosis and dysfunction in a murine model of diabetes. 

PMID- 26209014
TI  - [Evaluation of Nurse Demand Management in Primary Care].
AB  - OBJECTIVE: to evaluate the health outcomes of nurse demand management on
      unscheduled patients in a Primary Care Centre, following a clinical guide
      designed by the whole primary care team. DESIGN: Cross-sectional study. SETTING:
      A primary care team from Castelldefels. Barcelona, Spain. PARTICIPANTS: A random
      sample of 558 patients requesting a consultation for the same day in a Primary
      Care setting, attended between May 1st, 2011 and January 31st, 2012.
      INTERVENTION: The guide includes 23 health problems that can be dealt by a nurse
      autonomously, 18 of them possibly requiring an emergency intervention, and shared
      decision with the physician. Each health problem is divided into three sections:
      a) a brief definition of the problem; b) an intervention algorithm; and c)
      nursing diagnoses of North American Nursing Diagnosis Association for each health
      problem and a description of the possible nursing interventions. RESULTS: We
      studied 558 patients with a mean age of 42.5 years old (SD 17.7). The most
      commonly consulted problems were upper respiratory tract symptoms (19.4%),
      followed by nausea/vomiting (16.5%), and burns/wounds (12.5%). 73.3% of the
      problems were resolved autonomously by a nurse. 65,8% of the patients attended
      received health advice. DISCUSSION: Nurse demand management has shown to be
      highly effective at handling the conditions attended, while it provides a high
      percentage of health advice and education during consultations.

PMID- 26209016
TI  - Strategies for weaning from mechanical ventilation: a state of the art review.
AB  - Identification and adoption of strategies to promote timely and successful
      weaning from mechanical ventilation remain a research and quality improvement
      priority. The most important steps in the weaning process to prevent unnecessary
      prolongation of mechanical ventilation are timely recognition of both readiness
      to wean and readiness to extubate. Strategies shown to be effective in promoting
      timely weaning include weaning protocols and use of spontaneous breathing trials.
      This review explores various other strategies that also may promote timely and
      successful weaning including bundling of spontaneous breathing trials with
      sedation and delirium monitoring/management as well as early mobility, the use of
      automated weaning systems and modes that improve patient-ventilator interaction,
      mechanical insufflation-exsufflation as a weaning adjunct, early extubation to
      non-invasive ventilation and high flow humidified oxygen. As most critically ill
      patients requiring mechanical ventilation will tolerate extubation with minimal
      weaning, identification of strategies to improve management of those patients
      experiencing difficult and prolonged weaning should be a priority for clinical
      practice, quality improvement initiatives and weaning research.

PMID- 26209015
TI  - Acute phase proteins as local biomarkers of respiratory infection in calves.
AB  - BACKGROUND: Cumulating reports suggest that acute phase proteins (APPs) do not
      only play a role as systemic inflammatory mediators, but are also expressed in
      different tissues as local reaction to inflammatory stimuli. The present study
      aimed to evaluate presence and changes in luminal lung concentrations of the APPs
      haptoglobin (Hp), lipopolysaccharide binding protein (LBP), C-reactive protein
      (CRP), and lactoferrin (Lf) in calves with an acute respiratory disease
      experimentally induced by Chlamydia (C.) psittaci. RESULTS: Intra-bronchial
      inoculation of the pathogen resulted in a consistent respiratory illness. In
      venous blood of the infected calves (n = 13), concentrations of plasma proteins
      and serum LBP were assessed (i) before exposure and (ii) 8 times within 14 days
      after inoculation (dpi). Increasing clinical illness correlated significantly
      with increasing LBP-and decreasing albumin concentrations in blood, both
      verifying a systemic acute phase response. Broncho-alveolar lavage fluid (BALF)
      was obtained from all 13 calves experimentally infected with C. psittaci at 4, 9
      and 14 dpi, and from 6 uninfected healthy calves. Concentrations of bovine serum
      albumin (BSA), Hp, LBP, CRP and Lf in BALF were determined by ELISA. In infected
      animals, absolute concentrations of LBP and Hp in BALF correlated significantly
      with the respiratory score. The quotient [LBP]/[BSA] in BALF peaked significantly
      in acutely infected animals (4 dpi), showed a time-dependent decrease during the
      recovery phase (9-14 dpi), and was significantly higher compared to healthy
      controls. Concentrations of Hp and Lf in BALF as well as [Hp]/[BSA]--and
      [Lf]/[BSA]-quotients decreased during the study in infected animals, but were
      never higher than in healthy controls. CRP concentrations and [CRP]/[BSA]
      quotient did not express significant differences between infected and healthy
      animals or during the course of infection. CONCLUSION: In conclusion, absolute
      concentrations of LBP in blood and BALF as well as the quotient [LBP]/[BSA] in
      BALF perfectly paralleled the clinical course of respiratory illness after
      infection. Beside LBP, the suitability of Hp and Lf as local biomarkers of
      respiratory infections in cattle and their role in the local response to
      pathogens is worth further investigation, while CRP does not seem to play a role
      in local defense mechanisms of the bovine lung.

PMID- 26209017
TI  - Comparison of the Lunar Prodigy and iDXA Dual-Energy X-ray Absorptiometers for
      Assessing Total and Regional Body Composition.
AB  - The objective of the study was to assess the agreement of the Lunar Prodigy with
      the newer Lunar iDXA dual-energy X-ray absorptiometer for determining total body
      and regional (arms, legs, trunk) bone mineral density (BMD), bone mineral content
      (BMC), fat mass (FM), lean tissue mass (LTM), total body mass, and percent fat.
      Ninety-two healthy adult males (n = 36) and females (n = 56) were scanned
      consecutively on the iDXA and the Prodigy dual-energy X-ray absorptiometers. For
      iDXA, relative to Prodigy, paired t tests indicated significantly lower estimates
      for total body and regional BMD and BMC (p < 0.001). Measures of total body and
      trunk FM, LTM, and percent fat did not differ between the instruments. In
      regional analyses, estimates of FM and percent fat were greater, and that of LTM
      was lower, in the arms (p < 0.001). In contrast, iDXA estimates of LTM were
      higher in the legs (p < 0.001). All body composition measures were significantly
      correlated (p < 0.001). Bland-Altman analyses indicated that significant bias
      existed between iDXA and Prodigy for total body and regional BMD estimates (p <
      0.001) such that iDXA underestimated BMD to a greater extent in persons with
      higher values. In addition, iDXA overestimation bias existed for FM in total
      body, arms, and legs, and the overestimation was primarily observed in
      participants with greater body fat (p < 0.001). When combining or comparing data
      from iDXA with those from Prodigy, investigators should be aware that certain
      total body and regional estimates are significantly different. The greatest
      percent differences were observed for arm BMD, FM, and percent fat.

PMID- 26209018
TI  - Dropping the Ball and Falling Off the Care Wagon. Factors Correlating With
      Nonadherence to Secondary Fracture Prevention Programs.
AB  - Health care systems and hospitals in several countries have implemented Fracture
      Liaison Services (FLSs). Success rates of FLSs with regard to osteoporosis
      assessment and treatment, fracture reduction, and adherence to osteoporosis
      medications have been reported by several groups including ours. A significant
      drop-out rate among patients in these programs may occur. This has not been
      evaluated before. We explored the factors correlating with nonadherence among a
      multiethnic population of patients in the FLS at our institution, the largest
      tertiary teaching hospital in South East Asia. Our secondary objective was to
      explore whether patients who defaulted follow-up visits continued to be compliant
      with medications. A retrospective analysis of our FLS's computerized database was
      performed. Of 938 patients followed up more than 2 years, 237 defaulted at
      various time points. A significant percentage of patients who dropped out of the
      program opined that it was because the follow-up visits were too time consuming.
      Non-Chinese patients were more likely than Chinese (adjusted hazard ratio [aHR] =
      1.98, 1.33-2.94), patients with primary school education and below were more
      likely than those with secondary school and above education (aHR = 1.65, 1.11
      2.45) and those with nonvertebral and/or multiple fractures were more likely than
      those with spine fractures (aHR = 1.38, 1.06-1.81) to be nonadherent. A fraction
      of patients who defaulted continued to fill osteoporosis medication
      prescriptions. Median medication possession ratio among the patients who
      defaulted was 12.3% (interquartile range: 4.1%-36.7%) at 2 years. Persistence
      ranged from 15.1% to 20.8% and from 1.9% to 7.5% at 1 and 2 years, respectively
      after defaulting from the program. Our study, which to the best of our knowledge
      is the first of its kind, provides insight into the factors correlating with
      nonadherence to FLSs. Knowledge of the challenges faced by patients may be of
      help to health care providers interested in developing FLSs. 

PMID- 26209019
TI  - Microbial diseases of the genital system of rams or bucks.
AB  - Objective of the present paper is to review microbial diseases of the genital
      system of male small ruminants. The paper reviews the infections and the diseases
      by taking an organ approach within the genital system, whilst relevant health
      management actions are also discussed. Diseases of the genital organs of male
      small ruminants include orchitis, of bacterial or viral aetiology, epididymitis,
      primarily caused by Brucella ovis, by other bacteria as well (e.g.,
      Actinobacillus seminis, Haemophilus somni), infections of the accessory glands,
      orf, other infections of the penis or prepuce and infections of the scrotum. The
      health management of rams/bucks include the appropriate diagnostic
      investigations, the relevant therapeutic approaches and, finally, the preventive
      measures. 

PMID- 26209020
TI  - Novel pharmaceuticals in the management of postoperative pain.
AB  - Novel pharmaceutical advances in postoperative pain management include both non
      opioid adjuvants as well as opioid analgesics. Optimizing postoperative
      analgesics includes improving onset of action, matching duration of analgesia to
      the setting of use, and minimizing adverse events. To improve on the current
      standard of care, the physicochemical properties of new analgesics and route of
      administration must be taken into consideration in order to achieve these three
      goals. Appropriately, patient satisfaction with postoperative pain is a key
      emphasis in hospital-focused patient satisfaction surveys, thereby focusing much
      needed attention on improvement of care in the postoperative setting from both an
      analgesic efficacy and safety standpoint. 

PMID- 26209021
TI  - Evolutionary dynamics of a polymorphic self-replicator population with a finite
      population size and hyper mutation rate.
AB  - Self-replicating biomolecules, subject to experimental evolution, exhibit hyper
      mutation rates where the genotypes of most offspring have at least a one point
      mutation. Thus, we formulated the evolutionary dynamics of an asexual self
      replicator population with a finite population size and hyper mutation rate,
      based on the probability density of fitnesses (fitness distribution) for the
      evolving population. As a case study, we used a Kauffman's "NK fitness
      landscape". We deduced recurrence relations for the first three cumulants of the
      fitness distribution and compared them with the results of computer simulations.
      We found that the evolutionary dynamics is classified in terms of two modes of
      selection: the "radical mode" and the "gentle mode". In the radical mode, only a
      small number of genotypes with the highest or near highest fitness values can
      leave offspring. In the gentle mode, genotypes with moderate fitness values can
      leave offspring. We clarified how the evolutionary equilibrium and climbing rate
      depend on given parameters such as gradient and ruggedness of the landscape,
      mutation rate and population size, in terms of the two modes of selection.
      Roughly, the radical mode conducts the fast climbing but attains to the
      stationary states with low fitness, while the gentle mode conducts the slow
      climbing but attains to the stationary states with high fitness.

PMID- 26209022
TI  - SFM: A novel sequence-based fusion method for disease genes identification and
      prioritization.
AB  - The identification of disease genes from human genome is of great importance to
      improve diagnosis and treatment of disease. Several machine learning methods have
      been introduced to identify disease genes. However, these methods mostly differ
      in the prior knowledge used to construct the feature vector for each instance
      (gene), the ways of selecting negative data (non-disease genes) where there is no
      investigational approach to find them and the classification methods used to make
      the final decision. In this work, a novel Sequence-based fusion method (SFM) is
      proposed to identify disease genes. In this regard, unlike existing methods,
      instead of using a noisy and incomplete prior-knowledge, the amino acid sequence
      of the proteins which is universal data has been carried out to present the genes
      (proteins) into four different feature vectors. To select more likely negative
      data from candidate genes, the intersection set of four negative sets which are
      generated using distance approach is considered. Then, Decision Tree (C4.5) has
      been applied as a fusion method to combine the results of four independent state
      of the-art predictors based on support vector machine (SVM) algorithm, and to
      make the final decision. The experimental results of the proposed method have
      been evaluated by some standard measures. The results indicate the precision,
      recall and F-measure of 82.6%, 85.6% and 84, respectively. These results confirm
      the efficiency and validity of the proposed method. 

PMID- 26209023
TI  - CYP21A2 genetics: When genotype does not fit phenotype.

PMID- 26209024
TI  - Thoracic epidural blood patch with high volume blood for cerebrospinal fluid
      leakage of cervical spine (C2-3) complicated with spontaneous intracranial
      hypotension.
AB  - Acute and chronic subdural hemorrhage in a 33 year old woman with severe headache
      from occipital to frontal regions and dull neck pain was diagnosed on magnetic
      resonance image, which revealed cerebrospinal fluid leakage at C2-3 with
      spontaneous intracranial hypotension. Successful treatment was performed by
      epidural blood patch from the level of T7-T8 with injection of 20 mL of
      autologous blood. 

PMID- 26209026
TI  - Invasive Pleomorphic Lobular Carcinoma of the Breast: Pathologic, Clinical, and
      Therapeutic Considerations.
AB  - Pleomorphic lobular carcinoma is an uncommon form of breast cancer and a subtype
      of invasive lobular carcinoma. It has unique histopathologic features that
      translate to a more aggressive phenotype with an associated poor prognosis.
      Unlike classical invasive lobular carcinoma, it can lose estrogen and
      progesterone receptor expression and demonstrate HER-2/neu amplification. It
      remains to be determined, however, whether the pleomorphic histology
      independently predicts a worse outcome or whether other known associated negative
      prognostic factors such as larger tumor size, increased metastatic disease, and
      associated worse molecular subtypes commonly present in pleomorphic carcinoma
      account for the poor prognosis. Here we present an updated review of the unique
      pathologic and clinical features of pleomorphic lobular carcinoma needed to guide
      management for women with this subtype of cancer. 

PMID- 26209025
TI  - It's LiFe! Mobile and Web-Based Monitoring and Feedback Tool Embedded in Primary
      Care Increases Physical Activity: A Cluster Randomized Controlled Trial.
AB  - BACKGROUND: Physical inactivity is a major public health problem. The It's LiFe!
      monitoring and feedback tool embedded in the Self-Management Support Program
      (SSP) is an attempt to stimulate physical activity in people with chronic
      obstructive pulmonary disease or type 2 diabetes treated in primary care.
      OBJECTIVE: Our aim was to evaluate whether the SSP combined with the use of the
      monitoring and feedback tool leads to more physical activity compared to usual
      care and to evaluate the additional effect of using this tool on top of the SSP.
      METHODS: This was a three-armed cluster randomised controlled trial. Twenty four
      family practices were randomly assigned to one of three groups in which
      participants received the tool + SSP (group 1), the SSP (group 2), or care as
      usual (group 3). The primary outcome measure was minutes of physical activity per
      day. The secondary outcomes were general and exercise self-efficacy and quality
      of life. Outcomes were measured at baseline after the intervention (4-6 months),
      and 3 months thereafter. RESULTS: The group that received the entire intervention
      (tool + SSP) showed more physical activity directly after the intervention than
      Group 3 (mean difference 11.73, 95% CI 6.21-17.25; P<.001), and Group 2 (mean
      difference 7.86, 95% CI 2.18-13.54; P=.003). Three months after the intervention,
      this effect was still present and significant (compared to Group 3: mean
      difference 10.59, 95% CI 4.94-16.25; P<.001; compared to Group 2: mean difference
      9.41, 95% CI 3.70-15.11; P<.001). There was no significant difference in effect
      between Groups 2 and 3 on both time points. There was no interaction effect for
      disease type. CONCLUSIONS: The combination of counseling with the tool proved an
      effective way to stimulate physical activity. Counseling without the tool was not
      effective. Future research about the cost-effectiveness and application under
      more tailored conditions and in other target groups is recommended. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01867970,
      https://clinicaltrials.gov/ct2/show/NCT01867970 (archived by WebCite at
      http://www.webcitation.org/6a2qR5BSr).

PMID- 26209027
TI  - Solution structure of the PhoP DNA-binding domain from Mycobacterium
      tuberculosis.

PMID- 26209028
TI  - Neuropeptide W modulation of gastric vagal afferent mechanosensitivity: Impact of
      age and sex.
AB  - AIM: Gastric vagal afferents are activated in response to mechanical stimulation,
      an effect attenuated by neuropeptide W (NPW) in 20-week-old female mice. In this
      study we aimed to determine whether there were age and sex dependent effects of
      NPW on gastric vagal afferent mechanosensitivity. METHODS: An in vitro gastro
      oesophageal preparation was used to determine the effect of NPW on gastric vagal
      afferent mechanosensitivity from 8 and 20-week-old male and female C57BL/6 mice.
      Retrograde tracing and laser capture microdissection were used to selectively
      collect gastric vagal afferent cell bodies. Expression of NPW in the gastric
      mucosa and its receptor, GPR7, in gastric vagal afferent cell bodies was
      determined using quantitative RT-PCR. RESULTS: NPW inhibited gastric tension
      sensitive vagal afferents from 20-week-old male and female mice, but not 8-week
      old mice. In contrast, NPW inhibited the mechanosensitivity of gastric mucosal
      vagal afferents in 8-week-old male and female mice, but not 20-week-old mice. NPW
      mRNA expression in the gastric mucosa was higher in 20-week-old male mice
      compared to 8-week-old male mice. GPR7 mRNA expression in vagal afferent neurons
      innervating the gastric muscular layers was higher in 20-week-old mice compared
      to 8-week-old mice in both sexes. CONCLUSION: The inhibitory effect of NPW on
      gastric tension sensitive and mucosal vagal afferents is age but not sex
      dependent. These findings suggest that the physiological role of NPW varies
      depending on the age of the mice.

PMID- 26209029
TI  - Laparoscopic peritoneal lavage for perforated diverticulitis: in search of
      evidence.

PMID- 26209030
TI  - Laparoscopic peritoneal lavage or sigmoidectomy for perforated diverticulitis
      with purulent peritonitis: a multicentre, parallel-group, randomised, open-label
      trial.
AB  - BACKGROUND: Case series suggest that laparoscopic peritoneal lavage might be a
      promising alternative to sigmoidectomy in patients with perforated
      diverticulitis. We aimed to assess the superiority of laparoscopic lavage
      compared with sigmoidectomy in patients with purulent perforated diverticulitis,
      with respect to overall long-term morbidity and mortality. METHODS: We did a
      multicentre, parallel-group, randomised, open-label trial in 34 teaching
      hospitals and eight academic hospitals in Belgium, Italy, and the Netherlands
      (the Ladies trial). The Ladies trial is split into two groups: the LOLA group
      comparing laparoscopic lavage with sigmoidectomy and the DIVA group comparing
      Hartmann's procedure with sigmoidectomy plus primary anastomosis. The DIVA
      section of this trial is still underway but here we report the results of the
      LOLA section. Patients with purulent perforated diverticulitis were enrolled for
      LOLA, excluding patients with faecal peritonitis, aged older than 85 years, with
      high-dose steroid use (>=20 mg daily), and haemodynamic instability. Patients
      were randomly assigned (2:1:1; stratified by age [<60 years vs >=60 years]) using
      secure online computer randomisation to laparoscopic lavage, Hartmann's
      procedure, or primary anastomosis in a parallel design after diagnostic
      laparoscopy. Patients were analysed according to a modified intention-to-treat
      principle and were followed up after the index operation at least once in the
      outpatient setting and after sigmoidoscopy and stoma reversal, according to local
      protocols. The primary endpoint was a composite endpoint of major morbidity and
      mortality within 12 months. This trial is registered with ClinicalTrials.gov,
      number NCT01317485. FINDINGS: Between July 1, 2010, and Feb 22, 2013, 90 patients
      were randomly assigned in the LOLA section of the Ladies trial when the study was
      terminated by the data and safety monitoring board because of an increased event
      rate in the lavage group. Two patients were excluded for protocol violations. The
      primary endpoint occurred in 30 (67%) of 45 patients in the lavage group and 25
      (60%) of 42 patients in the sigmoidectomy group (odds ratio 1.28, 95% CI 0.54
      3.03, p=0.58). By 12 months, four patients had died after lavage and six patients
      had died after sigmoidectomy (p=0.43). INTERPRETATION: Laparoscopic lavage is not
      superior to sigmoidectomy for the treatment of purulent perforated
      diverticulitis. FUNDING: Netherlands Organisation for Health Research and
      Development.

PMID- 26209031
TI  - An acid-stable bacterial laccase identified from the endophyte Pantoea ananatis
      Sd-1 genome exhibiting lignin degradation and dye decolorization abilities.
AB  - OBJECTIVES: Isolation and identification of a novel laccase (namely Lac4) with
      various industrial applications potentials from an endophytical bacterium.
      RESULTS: Endophyte Sd-1 cultured in rice straw showed intra- and extra-cellular
      laccase activities. Genomic analysis of Sd-1 identified four putative laccases,
      Lac1 to Lac4. However, only Lac4 contains the complete signature sequence of
      laccase and shares at most 64 % sequence identity with other characterized
      bacterial multi-copper oxidases. Recombinant Lac4 can oxidize non-phenolic and
      phenolic compounds under acidic conditions and at 30-50  degrees C; Km values of
      Lac4 for ABTS at pH 2.5 and for guaiacol at pH 4.5 were 1 +/- 0.15 and 6.1 +/-
      1.7 mM, respectively. The activity of Lac4 was stimulated by 0.8 mM Cu(2+) and 5
      mM Fe(2+). In addition, Lac4 could decolorize various synthetic dyes and exhibit
      the degradation rate of 38 % for lignin. CONCLUSIONS: The data suggest that Lac4
      possesses promising biotechnological potentials.

PMID- 26209032
TI  - Isolation and characterization of an interactive culture of two Paenibacillus
      species with moderately thermophilic desulfurization ability.
AB  - OBJECTIVE: To isolate and characterize novel thermophilic bacteria capable of
      biodesulfurization of petroleum. RESULTS: A culture containing two Paenibacillus
      spp. (denoted "32O-W" and "32O-Y") was isolated by repeated passage of a soil
      sample at up to 55  degrees C in medium containing dibenzothiophene (DBT) as
      sulfur source. Only 32O-Y metabolized DBT, apparently via the 4S pathway; maximum
      activity occurred from 40 to 45  degrees C, with some activity up to at least 50 
      degrees C. 32O-W enhanced DBT metabolism by 32O-Y (by 22-74 % at 40-50  degrees
      C). With sulfate as sulfur source, 32O-Y and 32O-W grew well up to 58 and 63 
      degrees C, respectively. Selection of a mixed culture of 32O-Y and 32O-W at 54 
      degrees C increased DBT metabolism 36-42 % from 40 to 45  degrees C. Genome
      sequencing identified desulfurization gene homologs in the strains consistent
      with their desulfurization properties. CONCLUSION: The 32O-Y/32O-W culture may be
      a useful starting point for development of an improved thermophilic petroleum
      biodesulfurization process.

PMID- 26209033
TI  - Rapid and environmentally-friendly extraction of carotenoids from Blakeslea
      trispora.
AB  - OBJECTIVE: A rapid and environmentally-friendly method of carotenoid extraction
      from Blakeslea trispora was performed using low-pressure steam explosion for cell
      disruption and ethyl lactate for the extraction. RESULTS: Response surface
      methodology determined the optimal extraction conditions to obtain the maximum
      carotenoid yield. These optimal conditions consisted of low-pressure steam
      explosion at 0.2 MPa for 4.4 min, followed by extraction with ethyl lactate at a
      ratio of 1:25 at 39  degrees C for 45 min. Optimal technology was used, and the
      total carotenoid yield reached 95.6 %. CONCLUSION: In contrast to previously
      methods, the time-consuming drying process was eliminated and the extraction time
      was significantly decreased. Ethyl lactate is an environmentally-friendly solvent
      with low toxicity in this method.

PMID- 26209034
TI  - [Graft-versus-host disease, a rare complication of lung transplantation].
AB  - Graft-versus-host disease (GVHD) is a classic and frequent multisystemic
      complication of bone marrow allografts. It has also been reported after the
      transplantation of solid organs such as the liver or gut. Recent cases of GVHD
      have been reported after lung and heart-lung transplant. Skin, liver,
      gastrointestinal tract and bone marrow are the organ preferentially affected by
      GVHD. Corticosteroid is the first line treatment of GVHD. The prognosis reported
      in solid organ transplants is poor with infectious complications favoured by
      immunosuppressive therapy. In this article, we report a case of a patient with
      cystic fibrosis who presented a probable GVHD 18 months after a lung transplant
      and a literature review of similar cases. 

PMID- 26209035
TI  - Device Malfunction with the da Vinci S Surgical System and Impact on Surgical
      Procedures: Could Device Aging be Responsible?

PMID- 26209036
TI  - Predicting Response to Intravesical Bacillus Calmette-Guerin Immunotherapy: Are
      We Moving Forward?

PMID- 26209037
TI  - Superior Vena Cava Lipoma in an Asymptomatic Man.
AB  - A 58-year-old asymptomatic male smoker, underwent computed tomography of the
      chest for lung cancer screening. Unenhanced CT showed a hypodense elongated
      lesion with fat density within the superior vena cava (SVC). Magnetic resonance
      imaging was performed and confirmed the fatty nature of the lesion. Surgical
      resection of the lesion was performed and histopathological evaluation confirmed
      the diagnosis of SVC lipoma. 

PMID- 26209038
TI  - Sitagliptin, a dipeptidyl peptidase-4 inhibitor, increases the number of
      circulating CD34+CXCR4+ cells in patients with type 2 diabetes.
AB  - We investigated the effects of sitagliptin, a dipeptidyl peptidase (DPP)-4
      inhibitor, on the number of circulating CD34(+)CXCR4(+)cells, a candidate for
      endothelial progenitor cells (EPCs), plasma levels of stromal cell-derived factor
      (SDF)-1alpha, a ligand for CXCR4 receptor and a substrate for DPP-4, and plasma
      levels of interferon-inducible protein (IP)-10, for a substrate for DPP-4, in
      patients with type 2 diabetes. We studied 30 consecutive patients with type 2
      diabetes who had poor glycemic control despite treatment with metformin and/or
      sulfonylurea. Thirty diabetic patients were randomized in a 2:1 ratio into a
      sitagliptin (50 mg/day) treatment group or an active placebo group (glimepiride 1
      mg/day) for 12 weeks. Both groups showed similar improvements in glycemic
      control. The number of circulating CD34(+)CXCR4(+) cells was increased from 30.5
      (20.0, 47.0)/10(6) cells at baseline to 55.5 (31.5, 80.5)/10(6) cells at 12 weeks
      of treatment with 50 mg/day sitagliptin (P = 0.0014), while showing no
      significant changes in patients treated with glimepiride. Plasma levels of SDF
      1alpha and IP-10, both physiological substrates of endogenous DPP-4 and
      chemokines, were significantly decreased at 12 weeks of sitagliptin treatment. In
      conclusion, treatment with sitagliptin increased the number of circulating
      CD34(+)CXCR4(+) cells by approximately 2-fold in patients with type 2 diabetes.

PMID- 26209039
TI  - Flavor perception test: evaluation in patients with Kallmann syndrome.
AB  - In Kallmann syndrome (KS), congenital hypogonadism is associated with olfactory
      impairment. To evaluate flavor perception-related disability in KS patients, 30
      patients with KS, 12 with normosmic hypogonadism (nIHH), 24 with acquired anosmia
      (AA), and 58 healthy controls entered the study. All participants completed
      questionnaires concerning dietary habits, olfaction-related quality of life
      (QoL), and self-determined olfactory, flavor, and taste abilities prior to
      undergoing standardized olfactometry and gustometry. Each subject underwent
      flavor testing, using orally administered aqueous aromatic solutions, identifying
      21 different compounds by choosing each out of 5 alternative items. Flavor score
      (FS) was calculated as the sum of correct answers (range 0-21). Flavor perception
      by self-assessment was similar between KS, nIHH, and controls, and was mostly
      reduced only in AA. FS was similar between KS (5.4 +/- 1.4) and AA (6.4 +/- 1.9),
      and lower than in nIHH (16.2 +/- 2.4, p < 0.001) and controls (16.8 +/- 1.7, p <
      0.0001). FS showed strong reproducibility, and correlated with olfactory scores
      in the overall population. KS and AA patients identified aromatics eliciting
      trigeminal stimulation better than pure odorants. Olfaction-related QoL was more
      impaired in AA than in KS. We report significant flavor impairment in KS. This
      contrasts with routine clinic evidence; KS patients, in contrast with AA, do not
      complain of flavor perception impairment, perhaps owing to the congenital nature
      of the dysfunction. Flavor perception impairment should be considered a specific
      KS disability, because of important detrimental effects on physical and mental
      health and on QoL. KS patients should also be advised of this impairment in order
      to prevent accidental and life-threatening events.

PMID- 26209040
TI  - A Comparison of Initial and Subsequent Follow-Up Strobovideolaryngoscopic
      Examinations in Singers.
AB  - OBJECTIVES: Previous studies have identified abnormal findings in up to 86.1% of
      singers on initial screening strobovideolaryngoscopy (SVL) examinations. No
      studies have compared the prevalence of abnormalities in singers on their
      subsequent follow-up SVL. Our study evaluates the frequency of these findings in
      both the initial and subsequent examinations. METHODS: Retrospective charts and
      SVL reports were reviewed on students from an opera conservatory from 1993 to
      2014. All students had initial screening SVL, but only students who later
      returned with acute voice complaints were included in the study (n = 51, 137
      follow-up visits). Normal SVL was defined as an examination without structural or
      functional abnormalities and reflux finding score <=7. Data were analyzed using
      the chi-square test. RESULTS: For initial examinations, 90.2% (including reflux)
      and 88.2% (excluding reflux) were abnormal. In follow-up examinations, 94.9%
      (including reflux) and 94.2% (excluding reflux) had abnormal findings, which
      included muscle tension dysphonia (40.1%), vocal fold (VF) masses (unilateral
      48.9%, bilateral 30.7%), vascular abnormalities (unilateral 27.0%, bilateral
      5.8%), sulcus (unilateral 17.5%, bilateral 5.1%), VF hypomobility (unilateral
      36.3%, bilateral 5.9%), phase (30.6%) and amplitude (44.8%) asymmetries, and
      glottic insufficiency (49.3%). Follow-up examinations revealed a significant
      increase in laryngopharyngeal reflux (chi(2) = 7.043; P < 0.05). CONCLUSIONS: We
      found a higher prevalence of abnormal findings compared with previous studies,
      which we attributed to a more inclusive definition of abnormal pathologies,
      improvements in SVL technology, and possibly increased experience with SVL
      interpretation. This high prevalence of abnormal findings in asymptomatic singers
      further supports the importance of baseline examinations.

PMID- 26209041
TI  - Behavior Assessment Battery: A Pilot Study of the Affective, Behavioral, and
      Cognitive Correlates Surrounding Spasmodic Dysphonia.
AB  - OBJECTIVE/HYPOTHESIS: This study investigates if adults with adductor spasmodic
      dysphonia (ADSD) report to experience anxiety and voice problems in particular
      situations, indicate the presence of negative speech-associated attitude, and/or
      the use of coping behaviors, by means of the Behavior Assessment Battery (BAB)
      modified for voice. METHODS: Thirty-two participants with ADSD and 32 adults
      without a voice disorder participated in this study. Each person completed four
      different BAB-Voice subtests. These standardized self-report tests are
      adaptations of the original BAB for people who stutter and explore an
      individual's speech-related belief, negative emotional reaction to and speech
      problems in particular speech situations, and the use of concomitant behaviors.
      RESULTS: Individuals with spasmodic dysphonia (SD) scored statistically
      significantly higher compared to typical speakers on all BAB subtests, indicating
      that individuals with SD report being significantly more anxious and experiencing
      significantly more voice problems in particular speech circumstances. They also
      reported a significant amount of negative speech-associated attitude and the use
      of a significant number of coping behaviors. Internal reliability was good for
      three of the four BAB subtests. CONCLUSIONS: The BAB is capable of reflecting the
      dimensions that surround the disorder of SD. The self-report measures have the
      potential to augment the observations made by the clinician and may lead to a
      more diverse and all-encompassing therapy for the person suffering from SD.
      Future research with a revised version of the BAB-Voice will continue to explore
      the validity, reliability, and replicability of the initial data.

PMID- 26209042
TI  - Intraductal Radiofrequency Ablation (RFA) for Pancreatic Cancer: Getting in Under
      the Wire?

PMID- 26209044
TI  - Delayed leg weakness due to peri-lesional neural degeneration in a patient with
      intracerebral haemorrhage: case report.

PMID- 26209046
TI  - Recent progresses on functional genomics in plant defense.

PMID- 26209045
TI  - Xenopus LAP2beta protein knockdown affects location of lamin B and nucleoporins
      and has effect on assembly of cell nucleus and cell viability.
AB  - Xenopus LAP2beta protein is the single isoform expressed in XTC cells. The
      protein localizes on heterochromatin clusters both at the nuclear envelope and
      inside a cell nucleus. The majority of XLAP2beta fraction neither colocalizes
      with TPX2 protein during interphase nor can be immunoprecipitated with XLAP2beta
      antibody. Knockdown of the XLAP2beta protein expression in XTC cells by synthetic
      siRNA and plasmid encoded siRNA resulted in nuclear abnormalities including
      changes in shape of nuclei, abnormal chromatin structure, loss of nuclear
      envelope, mislocalization of integral membrane proteins of INM such as lamin B2,
      mislocalization of nucleoporins, and cell death. Based on timing of cell death,
      we suggest mechanism associated with nucleus reassembly or with entry into
      mitosis. This confirms that Xenopus LAP2 protein is essential for the maintenance
      of cell nucleus integrity and the process of its reassembly after mitosis. 

PMID- 26209043
TI  - Adjuvant Endocrine Therapy and Bone Health in Breast Cancer.
AB  - Breast cancer is one of the most common malignancies of women. The majority of
      breast cancers express estrogen and/or progesterone receptors, permitting
      anticancer targeting strategies to reduce estrogen signaling in the cancer cells
      and thereby lowering the risk of breast cancer recurrence. The development of the
      selective estrogen receptor modulator (SERM) tamoxifen marked a significant
      milestone in breast cancer care that transcended older estrogen ablative
      strategies such as oophorectomy and ovarian irradiation. An unintended benefit of
      tamoxifen in postmenopausal women was bone density preservation. The third
      generation of aromatase inhibitors (AIs) have demonstrated superior efficacy to
      tamoxifen in improving disease-free survival in postmenopausal women. However,
      the AIs significantly increase bone resorption, reduce bone mineral density, and
      increase the risk of fracture above that of tamoxifen. As a consequence of this,
      clinical oncologists have assumed a larger role in the screening and treatment of
      the skeletal complications of breast cancer therapies. The key features of
      managing bone health in women with early stage breast cancer receiving adjuvant
      endocrine therapy are reviewed here.

PMID- 26209047
TI  - Native and non-native ruderals experience similar plant-soil feedbacks and
      neighbor effects in a system where they coexist.
AB  - Recent applications of coexistence theory to plant invasions posit that non
      natives establish in resident communities through either niche differences or
      traits conferring them with fitness advantages, the former being associated with
      coexistence and the latter with dominance and competitive exclusion. Plant-soil
      feedback is a mechanism that is known to explain both coexistence and dominance.
      In a system where natives and non-natives appear to coexist, we explored how
      plant-soil feedbacks affect the performance of nine native and nine non-native
      ruderal species-the prevalent life-history strategy among non-natives-when grown
      alone and with a phytometer. We also conducted field samplings to estimate the
      abundance of the 18 species, and related feedbacks to abundances. We found that
      groups of native and non-native ruderals displayed similar frequencies of
      negative, positive, and neutral feedbacks, resulting in no detectable differences
      between natives and non-natives. Likewise, the phytometer exerted comparable
      negative impacts on native and non-native plants, which were unchanged by plant
      soil feedbacks. Finally, feedbacks explained plant abundances only after removing
      one influential species which exhibited strong positive feedbacks but low
      abundance. Importantly, however, four out of five species with negative feedbacks
      were rare in the field. These findings suggest that soil feedbacks and plant
      plant interactions do not confer an advantage to non-native over native species,
      but do contribute to the observed coexistence of these groups in the system. By
      comparing natives and non-natives with overlapping abundances and strategies, our
      work broadens understanding of the consequences of plant-soil feedbacks in plant
      invasion and, more generally, coexistence within plant communities. 

PMID- 26209048
TI  - Laparoscopic pelvic sidewall dissection with combined resection of internal iliac
      vessels for local recurrence of rectal cancer.

PMID- 26209049
TI  - Quantitative differentiation of benign and malignant mammographic circumscribed
      masses using intensity histograms.
AB  - PURPOSE: To investigate the usefulness of density gradient of mammographic masses
      for differentiating benign from malignant lesions, particularly circumscribed
      masses, which are difficult to diagnose by shape. MATERIALS AND METHODS: Phantom
      experiments were performed and diagnostic mammography examinations were reviewed.
      Mammograms of three acrylic resin globes differing in hardness were acquired
      with/without applied pressure, and density gradients were examined on intensity
      histograms with standard deviation (SD) as a hardness index. Similar analyses
      were performed using clinical mammographic examinations of circumscribed mass
      lesions. The usefulness of SD for differentiating between benign and malignant
      lesions was investigated by ROC curve analysis and minimum/maximum values of
      malignant and benign lesions, respectively. RESULTS: For circumscribed masses (n
      = 196, benign, n = 176; malignant, n = 20), ROC analysis showed AUC = 0.786, with
      sensitivity = 70.0 %, specificity = 70.5 %, accuracy = 70.4 %, positive
      predictive value = 21.1 %, and negative predictive value = 95.4 % at SD = 64.46.
      Minimum and maximum SD of malignant and benign masses were 39.1 and 241.7,
      respectively. CONCLUSION: On mammography, circumscribed masses can be diagnosed
      with moderate accuracy using the intensity histogram SD. Masses with SD below the
      minimum of breast cancer can be roughly diagnosed as clinically benign.

PMID- 26209050
TI  - Potential impact of (rs 4645878) BAX promoter -248G>A and (rs 1042522) TP53
      72Arg>pro polymorphisms on epithelial ovarian cancer patients.
AB  - BACKGROUND: In India, Epithelial ovarian cancer has emerged as one of the most
      common malignancies affecting women. Tumor protein 53 (TP53) induces expression
      of the B cell lymphoma 2-associated X protein (BAX) gene by directly binding to
      the TP53-binding element in the BAX promoter. Therefore, we hypothesized that
      single-nucleotide polymorphism of BAX promoter -248G>A and TP53 72Arg>Pro gene
      may jointly contribute to ovarian cancer risk. OBJECTIVES: This study aimed at
      exploring the association of BAX promoter -248G>A and TP53 72Arg>Pro gene
      polymorphism with risk of developing EOC and its clinicopathological features and
      to evaluate gene-gene interaction of these two polymorphisms with risk of
      developing EOC. MATERIALS: The study was conducted on 70 Epithelial ovarian
      cancer patients and 70 healthy controls. Genotyping of p53 codon 72 and BAX
      promoter gene was examined by ASO-PCR and PICA-PCR, respectively. Odds ratios and
      95 % confidence intervals were calculated. RESULTS: We found an increased cancer
      risk associated with the BAX AA (ORs = 4.1, 95 %, CI = 1.23-13.97) genotype. An
      increased risk was also associated with the TP53 Pro/Pro (OR = 4.4, 95 % CI =
      1.40-13.99) and Arg/Pro genotype (OR = 2.3, 95 % CI = 1.13-4.86). The gene-gene
      interaction of these polymorphisms increased EOC risk in a more than additive
      manner (ORs for the presence of both BAX AA and TP53 Arg/Pro genotypes = 8.7, 95
      % CI = 1.66-45.48). BAX GG genotype was associated with adverse staging of cancer
      (P = 0.01). CONCLUSIONS: The findings suggest that polymorphism of BAX and TP53
      genes may be potential genetic modifiers for developing ovarian cancer.

PMID- 26209051
TI  - XIAP inhibitor Embelin inhibits bladder cancer survival and invasion in vitro.
AB  - BACKGROUND: Bladder cancer is the second most common urological malignancy around
      the world and is by far the most frequent urological malignancy in China. Embelin
      is an active compound identified as a novel X-chromosome-linked IAP (XIAP)
      inhibitor from the Embelia ribes that exhibits various medicinal effects
      including anti-inflammatory and anti-cancer activities. However, therapeutic
      effect of Embelin to human bladder cancer is not yet determined. METHODS: We
      evaluated the sensitizing potential of Embelin on inhibiting cell growth and
      migration of bladder cancer cell line by CCK8, Transwell, and Western Blot, and
      explored its related mechanism. We performed IHC staining of XIAP in 35 bladder
      cancer tissues and corresponding adjacent non-neoplastic tissues. RESULTS: XIAP
      was significantly upregulated in bladder cancer cases. When the concentration of
      Embelin was used respectively at 5, 10, 20, 25, and 35 umol/l, the survival of
      both T24 and 5637 cells decreased in a dose-/time-dependent manner. Our study
      confirmed that with the increase of concentration of Embelin, the expression
      levels of PI3K and p-Akt decreased significantly which further confirmed that
      Embelin inhibits cell growth by inducing apoptosis via PI3K/Akt pathway.
      CONCLUSIONS: Embelin may be developed into a novel and potential chemotherapeutic
      drug for bladder cancer.

PMID- 26209052
TI  - A vasoconstrictor response to COX-1-mediated prostacyclin synthesis in young rat
      renal arteries that increases in prehypertensive conditions.
AB  - This study aimed to determine whether prostacyclin (PGI2) functions as an
      endothelium-derived contracting factor (EDCF) in young rat renal arteries, and,
      if so, we wanted to examine the underlying mechanism(s) and how it changes in
      prehypertensive conditions. Vessels from Wistar-Kyoto (WKY) and prehypertensive
      spontaneously hypertensive rats (SHRs) of 25-28 days of age were isolated for
      functional and biochemical analyses. Result showed that following NO synthase
      (NOS) inhibition PGI2 and the thromboxane-prostanoid (TP) receptor agonist U
      46619 evoked contractions in young WKY renal arteries that were similar to those
      in prehypertensive SHRs. Meanwhile, the endothelial muscarinic receptor agonist
      ACh evoked an endothelium-dependent contraction under NOS-inhibited conditions
      and a production of the PGI2 metabolite 6-keto-PGF1alpha; both were sensitive to
      cyclooxygenase (COX) and/or COX-1 inhibition but higher in prehypertensive SHRs
      than in young WKYs. Interestingly, in WKY renal arteries PGI2 did not evoke
      relaxation even after TP receptor antagonism that diminished the contraction
      evoked by the agonist. Indeed, PGI2 (IP) receptors were not detected in the
      vessel with Western blot. Moreover, we noted that treatment with the nonselective
      COX inhibitor indomethacin, which was started at the prehypertensive stage,
      blunted the elevation of systolic blood pressure and reduced the heart-to-body
      ratio in SHR within 2 mo of treatment. These results demonstrate that due to
      scarcity of IP receptors, PGI2, which is derived mainly from COX-1-mediated
      metabolism, acts as an EDCF in young WKY renal arteries, and it increases in
      prehypertensive conditions. Also, our data revealed that COX inhibition starting
      from the prehypertensive stage has an antihypertensive effect in young SHRs. 

PMID- 26209053
TI  - The role of frataxin in doxorubicin-mediated cardiac hypertrophy.
AB  - Doxorubicin (DOX) is a highly effective anti-neoplastic agent; however, its
      cumulative dosing schedules are clinically limited by the development of
      cardiotoxicity. Previous studies have attributed the cause of DOX-mediated
      cardiotoxicity to mitochondrial iron accumulation and the ensuing reactive oxygen
      species (ROS) formation. The present study investigates the role of frataxin
      (FXN), a mitochondrial iron-sulfur biogenesis protein, and its role in
      development of DOX-mediated mitochondrial dysfunction. Athymic mice treated with
      DOX (5 mg/kg, 1 dose/wk with treatments, followed by 2-wk recovery) displayed
      left ventricular hypertrophy, as observed by impaired cardiac hemodynamic
      performance parameters. Furthermore, we also observed significant reduction in
      FXN expression in DOX-treated animals and H9C2 cardiomyoblast cell lines,
      resulting in increased mitochondrial iron accumulation and the ensuing ROS
      formation. This observation was paralleled in DOX-treated H9C2 cells by a
      significant reduction in the mitochondrial bioenergetics, as observed by the
      reduction of myocardial energy regulation. Surprisingly, similar results were
      observed in our FXN knockdown stable cell lines constructed by lentiviral
      technology using short hairpin RNA. To better understand the cardioprotective
      role of FXN against DOX, we constructed FXN overexpressing cardiomyoblasts, which
      displayed cardioprotection against mitochondrial iron accumulation, ROS
      formation, and reduction of mitochondrial bioenergetics. Lastly, our FXN
      overexpressing cardiomyoblasts were protected from DOX-mediated cardiac
      hypertrophy. Together, our findings reveal novel insights into the development of
      DOX-mediated cardiomyopathy. 

PMID- 26209055
TI  - Serum uric acid is associated with cardiac diastolic dysfunction among women with
      preserved ejection fraction.
AB  - Serum uric acid (SUA) is associated with the severity and prognosis of systolic
      heart failure. We investigated the potential association between SUA and cardiac
      diastolic dysfunction among total of 744 cardiac patients (202 women and 542 men)
      who had preserved left ventricular ejection fraction. Presence of diastolic
      dysfunction was assessed by echocardiographic data, plasma B-type natriuretic
      peptide concentration, and left ventricular hypertrophy. Univariate analysis
      showed that the prevalence of diastolic dysfunction increased with increasing SUA
      value in women, but not in men. When sex-nonspecific SUA quartiles were used,
      multivariate logistic regression analysis, among female patients who were not
      taking uric acid lowering medication, showed that the third (SUA, 5.7-6.4 mg) and
      the fourth (SUA, >=6.5 mg/dl) SUA quartiles were associated with diastolic
      dysfunction with an odds ratio of 3.25 (P < 0.05) and 8.06 (P < 0.001),
      respectively, when compared with the first SUA quartile (<=4.7 mg/dl). When sex
      specific SUA quartiles were used among these population, multivariate logistic
      regression analysis showed that the fourth SUA quartile (>=5.7 mg/dl) was
      associated with diastolic dysfunction with an odds ratio of 5.34 (P < 0.05) when
      compared with the first SUA quartile (<=4.1 mg/dl). By contrast, the relationship
      between SUA and diastolic dysfunction was not significant in men, irrespective of
      which of the sex-nonspecific or sex-specific SUA quartiles were used. These data
      indicated that among cardiac patients with preserved ejection fraction, SUA was
      significantly associated with diastolic dysfunction in women but not in men. 

PMID- 26209054
TI  - Attenuated sarcomere lengthening of the aged murine left ventricle observed using
      two-photon fluorescence microscopy.
AB  - The Frank-Starling mechanism, whereby increased diastolic filling leads to
      increased cardiac output, depends on increasing the sarcomere length (Ls) of
      cardiomyocytes. Ventricular stiffness increases with advancing age, yet it
      remains unclear how such changes in compliance impact sarcomere dynamics in the
      intact heart. We developed an isolated murine heart preparation to monitor Ls as
      a function of left ventricular pressure and tested the hypothesis that sarcomere
      lengthening in response to ventricular filling is impaired with advanced age.
      Mouse hearts isolated from young (3-6 mo) and aged (24-28 mo) C57BL/6 mice were
      perfused via the aorta under Ca(2+)-free conditions with the left ventricle
      cannulated to control filling pressure. Two-photon imaging of 4-{2-[6
      (dioctylamino)-2-naphthalenyl]ethenyl}1-(3-sulfopropyl)-pyridinium fluorescence
      was used to monitor t-tubule striations and obtain passive Ls between pressures
      of 0 and 40 mmHg. Ls values (in MUm, aged vs. young, respectively) were 2.02 +/-
      0.04 versus 2.01 +/- 0.02 at 0 mmHg, 2.13 +/- 0.04 versus 2.23 +/- 0.02 at 5
      mmHg, 2.21 +/- 0.03 versus 2.27 +/- 0.03 at 10 mmHg, and 2.28 +/- 0.02 versus
      2.36 +/- 0.01 at 40 mmHg, indicative of impaired sarcomere lengthening in aged
      hearts. Atomic force microscopy nanoindentation revealed that intact
      cardiomyocytes enzymatically isolated from aged hearts had increased stiffness
      compared with those of young hearts (elastic modulus: aged, 41.9 +/- 5.8 kPa vs.
      young, 18.6 +/- 3.3 kPa; P = 0.006). Impaired sarcomere lengthening during left
      ventricular filling may contribute to cardiac dysfunction with advancing age by
      attenuating the Frank-Starling mechanism and reducing stroke volume. 

PMID- 26209056
TI  - Value and determinants of the mean systemic filling pressure in critically ill
      patients.
AB  - Mean systemic filling pressure (Pmsf) is a major determinant of venous return.
      Its value is unknown in critically ill patients (ICU). Our objectives were to
      report Pmsf in critically ill patients and to look for its clinical determinants,
      if any. We performed a prospective study in 202 patients who died in the ICU with
      a central venous and/or arterial catheter. One minute after the heart stopped
      beating, intravascular pressures were recorded in the supine position after
      ventilator disconnection. Parameters at admission, during the ICU stay, and at
      the time of death were prospectively collected. One-minute Pmsf was 12.8 +/- 5.6
      mmHg. It did not differ according to gender, severity score, diagnosis at
      admission, fluid balance, need for and duration of mechanical ventilation, or
      length of stay. Nor was there any difference according to suspected cause of
      death, classified as shock (cardiogenic, septic, and hemorrhagic) and nonshock,
      although a large variability of values was observed. The presence of
      norepinephrine at the time of death (102 patients) was associated with a higher 1
      min Pmsf (14 +/- 6 vs. 11.4 +/- 4.5 mmHg), whereas the decision to forgo life
      sustaining therapy (34 patients) was associated with a lower 1-min Pmsf (10.9 +/-
      3.8 vs. 13.1 +/- 5.3 mmHg). In a multiple-regression analysis, norepinephrine
      (beta = 2.67, P = 0.0004) and age (beta = -0.061, P = 0.022) were associated with
      1-min Pmsf. One-minute Pmsf appeared highly variable without any difference
      according to the kind of shock and fluid balance, but was higher with
      norepinephrine. 

PMID- 26209058
TI  - ANG II-independent prorenin/(pro)renin receptor signaling pathways in the central
      nervous system.

PMID- 26209057
TI  - Arterial alpha2-Na+ pump expression influences blood pressure: lessons from
      novel, genetically engineered smooth muscle-specific alpha2 mice.
AB  - Arterial myocytes express alpha1-catalytic subunit isoform Na(+) pumps (75-80% of
      total), which are ouabain resistant in rodents, and high ouabain affinity alpha2
      Na(+) pumps. Mice with globally reduced alpha2-pumps (but not alpha1-pumps), mice
      with mutant ouabain-resistant alpha2-pumps, and mice with a smooth muscle (SM)
      specific alpha2-transgene (alpha2 (SM-Tg)) that induces overexpression all have
      altered blood pressure (BP) phenotypes. We generated alpha2 (SM-DN) mice with SM
      specific alpha2 (not alpha1) reduction (>50%) using nonfunctional dominant
      negative (DN) alpha2. We compared alpha2 (SM-DN) and alpha2 (SM-Tg) mice to
      controls to determine how arterial SM alpha2-pumps affect vasoconstriction and
      BP. alpha2 (SM-DN) mice had elevated basal mean BP (mean BP by telemetry: 117 +/-
      4 vs. 106 +/- 1 mmHg, n = 7/7, P < 0.01) and enhanced BP responses to chronic ANG
      II infusion (240 ng.kg(-1).min(-1)) and high (6%) NaCl. Several arterial Ca(2+)
      transporters, including Na(+)/Ca(2+) exchanger 1 (NCX1) and sarcoplasmic
      reticulum and plasma membrane Ca(2+) pumps [sarco(endo)plasmic reticulum Ca(2+)
      ATPase 2 (SERCA2) and plasma membrane Ca(2+)-ATPase 1 (PMCA1)], were also reduced
      (>50%). alpha2 (SM-DN) mouse isolated small arteries had reduced myogenic
      reactivity, perhaps because of reduced Ca(2+) transporter expression. In
      contrast, alpha2 (SM-Tg) mouse aortas overexpressed alpha2 (>2-fold), NCX1,
      SERCA2, and PMCA1 (43). alpha2 (SM-Tg) mice had reduced basal mean BP (104 +/- 1
      vs. 109 +/- 2 mmHg, n = 15/9, P < 0.02) and attenuated BP responses to chronic
      ANG II (300-400 ng.kg(-1).min(-1)) with or without 2% NaCl but normal myogenic
      reactivity. NCX1 expression was inversely related to basal BP in SM-alpha2
      engineered mice but was directly related in SM-NCX1 engineered mice. NCX1, which
      usually mediates arterial Ca(2+) entry, and alpha2-Na(+) pumps colocalize at
      plasma membrane-sarcoplasmic reticulum junctions and functionally couple via the
      local Na(+) gradient to help regulate cell Ca(2+). Altered Ca(2+) transporter
      expression in SM-alpha2 engineered mice apparently compensates to minimize Ca(2+)
      overload (alpha2 (SM-DN)) or depletion (alpha2 (SM-Tg)) and attenuate BP changes.
      In contrast, Ca(2+) transporter upregulation, observed in many rodent
      hypertension models, should enhance Ca(2+) entry and signaling and contribute
      significantly to BP elevation. 

PMID- 26209059
TI  - Mitigation of myocardial ischemia-reperfusion injury via HIF-1alpha-frataxin
      signaling.

PMID- 26209060
TI  - Left ventricular thrombus accompanied by intra-ventricular obstruction in a
      patient with acute cerebral embolism and hypereosinophilic syndrome.

PMID- 26209061
TI  - miR-25 promotes glioblastoma cell proliferation and invasion by directly
      targeting NEFL.
AB  - Glioblastoma multiforme (GBM) is the most malignant and common brain tumor; it is
      aggressive growth pattern means that GBM patients face a poor prognosis even when
      receiving the best available treatment modalities. In recent years, an increasing
      number of reports suggest that the discovery of microRNAs (miRNAs) might provide
      a novel therapeutic target for human cancers, including GBM. One miRNA in
      particular, microRNA-25 (miR-25), is overexpressed in several cancers, wherein
      accumulating evidence indicates that it functions as an oncogene. However, the
      function of miR-25 in GBM has not been totally elucidated. In this study, we
      demonstrated that miR-25 was significantly up-regulated in astrocytoma tissues
      and glioblastoma cell lines. In vitro studies further demonstrated that
      overexpressed miR-25 was able to promote, while its antisense oligos inhibited
      cell proliferation and invasion in U251 cells. Moreover, we identified
      neurofilament light polypeptide (NEFL) as a novel target molecule of miR-25. Also
      of note was the fact that NEFL was down-regulated with increased levels of miR-25
      expression in human astrocytoma clinical specimens. In addition, via the mTOR
      signaling pathway, NEFL-siRNA could significantly attenuate the inhibitory
      effects of knockdown miR-25 on the proliferation and invasion of U251 cells.
      Overall, our results showed an important role for miR-25 in regulating NEFL
      expression in GBM, and suggest that miR-25 could be a potential target for GBM
      treatment. 

PMID- 26209063
TI  - Migration of selected hydrocarbon contaminants into dry semolina and egg pasta
      packed in direct contact with virgin paperboard and polypropylene film.
AB  - Migration of mineral oil saturated hydrocarbons (MOSH), polyolefin oligomeric
      saturated hydrocarbons (POSH), and polyalphaolefins (PAO from hot melts) into dry
      semolina and egg pasta packed in direct contact with virgin paperboard or
      polypropylene (PP) flexible film was studied. Migration was monitored during
      shelf life (up to 24 months), through storage in a real supermarket (packs kept
      on shelves), conditions preventing exchange with the surrounding environment
      (packs wrapped in aluminium foil), and storage in a warehouse (packs inside of
      the transport box of corrugated board). Semolina pasta packed in virgin
      paperboard (without hot melts) had a MOSH content lower than 1.0 mg kg(-1). An
      increasing contamination with PAO belonging to the adhesives used to close the
      boxes was detected in egg pasta, wrapped in aluminium (1.5 and 5 mg kg(-1) after
      3 and 24 months, respectively). An environmental contribution to total
      hydrocarbon contamination was observed in egg pasta kept on shelves that, after 3
      and 24 months, showed levels of PAO/MOSH < C25 around 3 and 10 mg kg(-1),
      respectively. The migration of POSH from PP film into egg pasta wrapped in
      aluminium was around 0.6 mg kg(-1) after 3 months of contact and reached 1.7 mg
      kg(-1) after 24 months of contact. After 9 months of contact, semolina pasta
      packed in PP film and stored in the transport box showed that some MOSH migrated
      into the pasta from the board of the transport box (through the plastic film).

PMID- 26209064
TI  - Vaccine procurement during an influenza pandemic and the role of Advance Purchase
      Agreements: Lessons from 2009-H1N1.
AB  - Vaccines are hugely important tools in minimising the effect pandemic influenza
      could have on a population. The reforms introduced by the Pandemic Influenza
      Preparedness Framework are ill-suited to providing sufficient levels of access to
      vaccines to meet the needs of developing states, and as such developing states
      will continue to be reliant upon the traditional methods of vaccine procurement
      to procure the majority of the vaccines they required. Using procurement during
      2009-H1N1 as a case study, this paper examines the methods of procurement
      utilised by states in order to determine if the procurement tools available to
      developing states are sufficient to procure adequate levels of pandemic influenza
      vaccines. Particular focus is given to the role Advance Purchase Agreements
      (APAs) play in the procurement process. By exploring this case study it is
      possible to argue that these procurement methods are ineffective for developing
      states, and when the next influenza pandemic occurs, demand will once again
      outstrip supply globally, due to supply of vaccines being dominated by the
      developed states with APAs in place.

PMID- 26209062
TI  - Dual properties of hispidulin: antiproliferative effects on HepG2 cancer cells
      and selective inhibition of ABCG2 transport activity.
AB  - Hepatocellular carcinoma is the third most common cause of cancer-related deaths
      worldwide. Furthermore, the existing pharmacological-based treatments are
      insufficiently effective and generate many side effects. Hispidulin (6-methoxy
      5,7,4'-trihydroxyflavone) is a flavonoid found in various medicinal herbs that
      present antineoplastic properties. Here we evaluated how modulation of reactive
      oxygen species (ROS) and alterations of antioxidant defenses could be associated
      to the antiproliferative effects of hispidulin in HepG2 cells. In addition, we
      studied the inhibitory activity of hispidulin on the efflux of drugs mediated by
      ABC transporters involved in multidrug resistance. In order to understand the
      increase of intracellular ROS promoted by hispidulin, we investigated the mRNA
      expression levels and activities of antioxidant enzymes, and the GSH/GSSG ratio.
      We showed that hispidulin significantly down-regulated the transcription levels
      of catalase, leading to reduction of enzyme activity and decrease of the GSH
      content. We also observed that, in the presence of N-acetylcysteine or exogenous
      catalase, the proliferation was lowered back to the control levels. These data
      clearly indicate a strong involvement of intracellular ROS levels for triggering
      the antiproliferative effects. We also demonstrated that the inhibition produced
      by hispidulin on drug efflux was specific for ABCG2, since no effects were
      observed with ABCB1 and ABCC1. Furthermore, HepG2 cells were more sensitive to
      hispidulin-mediated cell death than immortalized L929 fibroblasts, suggesting a
      differential toxicity of this compound between tumor and non-tumor cell lines.
      Our results suggest that hispidulin constitutes a promising candidate to
      sensitize chemoresistant cancer cells overexpressing ABCG2. 

PMID- 26209065
TI  - Effect of taxanes-based induction chemotherapy in locoregionally advanced
      nasopharyngeal carcinoma: A large scale propensity-matched study.
AB  - OBJECTIVES: The effect of taxanes-based induction chemotherapy (IC) in
      locoregionally advanced nasopharyngeal carcinoma (LA-NPC) was quite contradictory
      in two phase II randomized controlled trials with small sample size. We aimed to
      investigate it in this large scale propensity-matched study. MATERIALS AND
      METHODS: Totally, 779 LA-NPC patients who underwent intensity-modulated
      radiotherapy (IMRT) plus concurrent chemotherapy with or without taxanes-based IC
      were included. Patients in both treatment arms were matched using propensity
      score matching method at the ratio of 1:1. Failure-free survival (FFS), overall
      survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse
      free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and
      Cox regression analysis. RESULTS: After matching, 534 patients were identified
      for analysis. In univariate analysis, both treatment arms resulted in parallel
      survival (4-years FFS 78.0% vs 74.1%, P = 0.304; OS 87.5% vs 87.3%, P = 0.595;
      DMFS 88.2% vs 84.4%, P = 0.154; and LRFS 91.2% vs 90.1%, P = 0.960). In
      multivariate analysis, taxanes-based IC did not improve any survival (P ? 0.139).
      And this association remained unchanged in subgroup analysis by age, sex and
      histology, and among patients with stage III and T4N0M0. But among patients with
      T4N1-2M0 and stage IVb, taxanes-based IC significantly prolonged the 4-year DMFS
      by 11.2% (86.1% vs 74.9%, P = 0.034), and marginally improved FFS (P = 0.133) and
      OS (P = 0.215) in both univariate and multivariate analysis. CONCLUSIONS: In this
      large scale propensity-matched study, LA-NPC patients could not benefit from
      taxanes-based IC on the whole. But the risk of distant metastasis significantly
      decreased by above 10% for patients with T4N1-2M0 and stage IVb.

PMID- 26209066
TI  - A systematic review of quality of life in head and neck cancer treated with
      surgery with or without adjuvant treatment.
AB  - Quality of life (QoL) is an important consideration in the management of head and
      neck cancers (HNC). We systematically reviewed the literature to assess the
      impact of curative surgical resection (+/- adjuvant therapy) of HNC on QoL.
      Eligible studies (participants>age 18 years, reported fully in English, and
      prospectively assessed QoL) were filtered using quality criteria, and classified
      according to the added value, using a published taxonomy. MEDLINE and EMBASE
      searching yielded 302 distinct reports, 49 met eligibility, and 26 met quality
      criteria. Among the eligible studies, achievement of certain quality criteria was
      poor: a priori hypothesis (8%), statistical accounting of missing data (8%),
      reporting of assessment interval (35%) and rationale for chosen measure (53%).
      The most frequent ways QoL added value were: understanding of treatment benefit
      and risk (100%), comparing treatments for QoL effect (92%) and advancing QoL
      research methodology (50%). QoL (physical/social functioning and various symptom
      domains) deteriorated with treatment, gradually recovering to baseline (cancer
      diagnosis) level. Swallowing, chewing, saliva, taste, eating disruption, and
      aesthetic deficits may persist. Advanced tumors, extensive surgical resection,
      need for flap reconstruction, neck dissection, and postoperative radiation are
      associated with worse QoL outcomes. Knowledge of these trends can be applied in
      shared decision making, identification of commonly faced QoL issues, and to
      develop and provide survivorship resources. Future research should focus on
      routinely incorporating QoL in randomized studies, reporting the result according
      to guidelines, and following knowledge translation principles to maximize the
      clinician's and patient's ability to use QoL data.

PMID- 26209067
TI  - A biological tool to assess flow connectivity in reference temporary streams from
      the Mediterranean Basin.
AB  - Many streams in the Mediterranean Basin have temporary flow regimes. While timing
      for seasonal drought is predictable, they undergo strong inter-annual variability
      in flow intensity. This high hydrological variability and associated ecological
      responses challenge the ecological status assessment of temporary streams,
      particularly when setting reference conditions. This study examined the effects
      of flow connectivity in aquatic macroinvertebrates from seven reference temporary
      streams across the Mediterranean Basin where hydrological variability and flow
      conditions are well studied. We tested for the effect of flow cessation on two
      streamflow indices and on community composition, and, by performing random forest
      and classification tree analyses we identified important biological predictors
      for classifying the aquatic state either as flowing or disconnected pools. Flow
      cessation was critical for one of the streamflow indices studied and for
      community composition. Macroinvertebrate families found to be important for
      classifying the aquatic state were Hydrophilidae, Simuliidae, Hydropsychidae,
      Planorbiidae, Heptageniidae and Gerridae. For biological traits, trait categories
      associated to feeding habits, food, locomotion and substrate relation were the
      most important and provided more accurate predictions compared to taxonomy. A
      combination of selected metrics and associated thresholds based on the most
      important biological predictors (i.e. Bio-AS Tool) were proposed in order to
      assess the aquatic state in reference temporary streams, especially in the
      absence of hydrological data. Although further development is needed, the tool
      can be of particular interest for monitoring, restoration, and conservation
      purposes, representing an important step towards an adequate management of
      temporary rivers not only in the Mediterranean Basin but also in other regions
      vulnerable to the effects of climate change. 

PMID- 26209068
TI  - Sealer: a scalable gap-closing application for finishing draft genomes.
AB  - BACKGROUND: While next-generation sequencing technologies have made sequencing
      genomes faster and more affordable, deciphering the complete genome sequence of
      an organism remains a significant bioinformatics challenge, especially for large
      genomes. Low sequence coverage, repetitive elements and short read length make de
      novo genome assembly difficult, often resulting in sequence and/or fragment
      "gaps" - uncharacterized nucleotide (N) stretches of unknown or estimated
      lengths. Some of these gaps can be closed by re-processing latent information in
      the raw reads. Even though there are several tools for closing gaps, they do not
      easily scale up to processing billion base pair genomes. RESULTS: Here we
      describe Sealer, a tool designed to close gaps within assembly scaffolds by
      navigating de Bruijn graphs represented by space-efficient Bloom filter data
      structures. We demonstrate how it scales to successfully close 50.8% and 13.8% of
      gaps in human (3 Gbp) and white spruce (20 Gbp) draft assemblies in under 30 and
      27 h, respectively - a feat that is not possible with other leading tools with
      the breadth of data used in our study. CONCLUSION: Sealer is an automated
      finishing application that uses the succinct Bloom filter representation of a de
      Bruijn graph to close gaps in draft assemblies, including that of very large
      genomes. We expect Sealer to have broad utility for finishing genomes across the
      tree of life, from bacterial genomes to large plant genomes and beyond. Sealer is
      available for download at https://github.com/bcgsc/abyss/tree/sealer-release.

PMID- 26209069
TI  - Sustained release of TGF-beta1 from biodegradable microparticles prepared by a
      new green process in CO2 medium.
AB  - The aim of this work was to encapsulate transforming growth factor beta1 (TGF
      beta1) into PLGA microparticles for regenerative medicine applications. TGF-beta1
      was firstly precipitated to ensure its stability during subsequent encapsulation
      within microparticles. A novel emulsification/extraction process in CO2 medium
      under mild conditions of pressure and temperature was used to encapsulate the
      protein. Interestingly, non-volatile injectable solvents, isosorbide dimethyl
      ether (DMI) and glycofurol (GF), were employed to precipitate the protein and to
      dissolve the polymer. Good encapsulation efficiency was obtained with preserved
      bioactivity of the protein. The microparticles were characterized in terms of
      size and zeta potential. In addition, the morphology and surface properties were
      determined using scanning electron microscopy (SEM) and atomic force microscopy
      (AFM) respectively. In vitro release study of the protein from microparticles was
      presented to assess the capacity of these systems to control the protein release.
      Moreover, cytotoxicity study was performed and showed an excellent
      cytocompatibility of the obtained microparticles. Thus, we described an effective
      and original process for TGF-beta1 encapsulation into PLGA microparticles. The
      obtained polymeric carriers could be used in many biomedical applications and
      were more specifically developed for cartilage regeneration. 

PMID- 26209070
TI  - Parenteral nanoemulsions as promising carriers for brain delivery of risperidone:
      Design, characterization and in vivo pharmacokinetic evaluation.
AB  - This paper describes design and evaluation of parenteral lecithin-based
      nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble
      psychopharmacological drug. The nanoemulsions were prepared through cold/hot high
      pressure homogenization and characterized regarding droplet size, polydispersity,
      surface charge, morphology, drug-vehicle interactions, and physical stability. To
      estimate the simultaneous influence of nanoemulsion formulation and preparation
      parameters--co-emulsifier type, aqueous phase type, homogenization temperature-
      on the critical quality attributes of developed nanoemulsions, a general
      factorial experimental design was applied. From the established design space and
      stability data, promising risperidone-loaded nanoemulsions (mean size about 160
      nm, size distribution <0.15, zeta potential around -50 mV), containing sodium
      oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol((r))
      HS15 as co-emulsifier, were produced by hot homogenization and their ability to
      improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic
      study demonstrated erratic brain profiles of risperidone following
      intraperitoneal administration in selected nanoemulsions, most probably due to
      their different droplet surface properties (different composition of the
      stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed
      increased (1.4-7.4-fold higher) risperidone brain availability compared to other
      nanoemulsions and drug solution, suggesting this nanoemulsion as a promising
      carrier worth exploring further for brain targeting.

PMID- 26209072
TI  - Development and validation of X-ray diffraction method for quantitative
      determination of crystallinity in warfarin sodium products.
AB  - The objective of this study was to develop and validate XRPD analytical method
      for the estimation of percent crystalline warfarin sodium present in drug
      products. Warfarin sodium (WS) is a clathrate containing Isopropyl alcohol
      entrapped in the crystalline structure. Four types of WS-excipient mixtures were
      prepared and used to make four formulations: M1 containing lactose monohydrate
      (WS: excipient 1:9), M2 containing anhydrous lactose (WS: excipient 1:9), M3
      containing lactose monohydrate (WS: excipient 1:21.5), M4 containing lactose
      anhydrous (WS: excipient 1:21.5). Thoroughly mixed powders were packed in the XRD
      sample holders and diffractogram were collected. Diffractogram in the 7-9 2theta
      were found to be distinctive as the peak intensity grows with increasing percent
      crystalline WS. This peak region was, therefore, used to validate the XRPD
      method. Validation parameters were evaluated for accuracy, precision, linearity,
      limit of detection (LOD), and limit of quantitation (LOQ). LOD and LOQ for M1,
      M2, M3, and M4 were 3.04, 3.17, 4.17, 4.49% and 9.21, 9.62, 12.65, 13.30%,
      respectively. The method was found to be linear with R(2)>0.99. With changing
      scan speed, X-ray power output, and type of sample holder, the method was found
      to be robust. Prediction of the % crystalline content of the WS sample with known
      crystallinity showed close agreement between actual and predicted value. In
      summary, XRPD method was validated, which can be used as a quantitative method
      for the estimation of % crystalline WS present in a drug product. 

PMID- 26209071
TI  - A novel glyceryl monoolein-bearing cubosomes for gambogenic acid: Preparation,
      cytotoxicity and intracellular uptake.
AB  - Lyotropic cubic liquid crystalline nanoparticles, also known as 'cubosomes', have
      been tested as effective carriers for a variety of drugs due to their ability to
      enhance delivery efficiency and reduced drug side effects. Cubosomes are
      colloidal carriers composed of biodegradable Glyceryl monooleate and F127. Being
      composed of well tolerable and physiological materials, these carriers are well
      tolerated, compatible and non-toxic. In this study, therefore, we developed a
      novel, water-soluble, glyceryl monooleate and F127 based multiblock copolymer for
      Gambogenic acid (GNA) by emulsion-evaporation and low temperature-solidification
      technique. Physicochemical properties, in vitro cytotoxicity, cellular uptake and
      in vivo pharmacokinetic of GNA-loaded cubosomes (GNA-Cubs) were investigated. The
      results revealed that GNA-Cubs were spherical or ellipsoidal monocellular by
      dynamic light scattering, meanwhile, 150-250nm in mean size with narrow
      polydispersity indexas determined by transmission electron microscopy. Small
      angle X-ray scattering indicated that GNA-Cubs retain the Pn3m cubic symmetry.
      Compared with GNA solution, GNA-Cubs exhibited markedly prolonged inhibitory
      activity in SMMC-7721 cells, as well as time-dependent increases in intra
      cellular uptake. Furthermore, in vivo pharmacokinetic study showed that the Cmax
      values and the AUC of GNA-Cubs were higher than GNA solution approximately 1.2
      fold and 9.1-fold, respectively. In conclusion, the results showed that the cubic
      liquid crystalline nanoparticles could be a potentially nanocarrier in the
      delivery of GNA for cancer therapy. 

PMID- 26209073
TI  - A calorimetric investigation of doxorubicin-polymer bead interactions.
AB  - Isothermal titration calorimetry (ITC) was utilised to investigate suitability of
      the technique to determine the stoichiometry and thermodynamics of the
      interactions that occur between a commonly used chemotherapeutic drug, namely
      doxorubicin, and a polymer bead-based drug delivery embolisation system (DC
      BeadTM). Six temperatures were selected for drug-polymer titrations (293-313 K)
      and in all cases an initially exothermic signal reverted to an endothermic
      response upon the saturation of the beads with drug. From these experiments, and
      subsequent calculations, the molar ratio of drug to SO3(-) (polymer) was found to
      be 0.4:1 at all temperatures studied. Enthalpic data was calculated from the raw
      ITC data with an average enthalpy of drug-polymer binding of - 14.8 kJ mol(-1) at
      293 K through to - 19.4 kJ mol(-1) at 313 K implying the process is enthalpically
      driven yet only affected by an increase in experimental temperature to a limited
      extent whereby an increase in experimental temperature results in a small
      increase in the negativity in change in enthalpy recorded. The application of ITC
      in this study (with its unique ability to monitor real-time interactions and
      facilitate stoichiometric calculations) resolves the lack of knowledge regarding
      the thermodynamics of this specific drug-polymer interaction. This study confirms
      that ITC is not only useful for this specific system, but also highlights the
      potential use of ITC for more general studies in this area.

PMID- 26209075
TI  - Comparative Effectiveness of the Different Treatment Modalities for Snoring.
AB  - OBJECTIVE: To evaluate what effects treatments of sleep-disordered breathing have
      on snoring and sleepiness: snoring surgery including osteotomies, mandibular
      advancement device (MAD), and continuous positive airway pressure (CPAP). STUDY
      DESIGN: Single-institution prospective comparative effectiveness trial. SETTING:
      University-affiliated secondary care teaching hospital. SUBJECTS AND METHODS: We
      prospectively studied 224 patients presenting with snoring at our department. All
      patients underwent detailed evaluation, including symptom questionnaires,
      clinical examination, polysomnography, and drug-induced sleep endoscopy. Based on
      these results, a treatment was proposed after multidisciplinary consultation.
      Treatment was evaluated through 4 questionnaires before treatment and 6 weeks and
      6 months after. Treatment success was defined as a global snoring visual analog
      scale score <=3 at 6 months. RESULTS: A total of 195 patients complied with full
      workup and were proposed treatment. The mean age was 46 +/- 11 years; the mean
      body mass index, 27 +/- 4; and the median apnea-hypopnea index, 10.0
      (interquartile range, 4.7-20.1). After discussion, 116 (59.5%) patients agreed to
      start treatment (46%, surgery; 26% MAD; 28% CPAP). All symptom scores, including
      Epworth Sleepiness Scale, decreased significantly for all treatments at 6 weeks
      and 6 months. Treatment was successful in 67% of the surgery patients, 67% of the
      MAD group, and 76% of the CPAP group. Only 6.7% reported an unchanged snoring
      score in the surgery group, compared with 13.6% in the MAD group and 9.6 % in the
      CPAP group. CONCLUSION: Multidisciplinary agreed-on treatment of snoring is
      effective across the proposed treatments.

PMID- 26209074
TI  - Human Structural Variation: Mechanisms of Chromosome Rearrangements.
AB  - Chromosome structural variation (SV) is a normal part of variation in the human
      genome, but some classes of SV can cause neurodevelopmental disorders. Analysis
      of the DNA sequence at SV breakpoints can reveal mutational mechanisms and risk
      factors for chromosome rearrangement. Large-scale SV breakpoint studies have
      become possible recently owing to advances in next-generation sequencing (NGS)
      including whole-genome sequencing (WGS). These findings have shed light on
      complex forms of SV such as triplications, inverted duplications, insertional
      translocations, and chromothripsis. Sequence-level breakpoint data resolve SV
      structure and determine how genes are disrupted, fused, and/or misregulated by
      breakpoints. Recent improvements in breakpoint sequencing have also revealed non
      allelic homologous recombination (NAHR) between paralogous long interspersed
      nuclear element (LINE) or human endogenous retrovirus (HERV) repeats as a cause
      of deletions, duplications, and translocations. This review covers the genomic
      organization of simple and complex constitutional SVs, as well as the molecular
      mechanisms of their formation. 

PMID- 26209076
TI  - Referral Patterns and Positive Airway Pressure Adherence upon Diagnosis of
      Obstructive Sleep Apnea.
AB  - OBJECTIVE: Obstructive sleep apnea (OSA) is a serious medical condition that adds
      to patient morbidity and mortality. Treatment with positive airway pressure (PAP)
      is the standard of care, but many patients refuse or do not tolerate PAP. Little
      is known about the subsequent management of these patients. We sought to
      understand what types of treatment, if any, adult patients with OSA receive who
      either fail or refuse PAP therapy within our institution. STUDY DESIGN:
      Retrospective chart review. SETTING: Academic hospital. SUBJECTS: All adult
      patients undergoing polysomnogram during the months of March and April 2010 (n =
      1174) who were diagnosed with OSA. METHODS: The electronic medical record was
      reviewed to determine the subsequent management of patients with a diagnosis of
      OSA, including tolerance or failure of PAP and referral to specialists upon
      intolerance. RESULTS: Of 1174 patients, 616 met inclusion criteria. Ultimately,
      260 (42%) had documented adherence to PAP. Of 241 untreated patients, 84 patients
      (35%) were referred for further attempts at management of diagnosed OSA. Nearly
      half of patients with diagnosed OSA did not have continued treatment or referral.
      CONCLUSION: To our knowledge, this is the first study to define the subsequent
      management of patients who have failed or refused PAP. Despite the known sequelae
      of OSA, clinicians are not treating a significant percentage of patients with
      diagnosed OSA. Those who fail to tolerate PAP therapy are unlikely to be referred
      for additional treatment. Therapies other than PAP may be warranted in this
      population.

PMID- 26209077
TI  - Comparison of Intraoperative versus Postoperative Parathyroid Hormone Levels to
      Predict Hypocalcemia Earlier after Total Thyroidectomy.
AB  - OBJECTIVE: To determine differences in the mean parathyroid hormone (PTH) levels
      for normocalcemic and hypocalcemic total thyroidectomy patients who were tested
      for PTH during the intraoperative or early postoperative period. DATA SOURCES:
      MEDLINE, the Cochrane Database, and other databases from 1960 to 2014 in the
      English language and specific to humans for relevant articles. REVIEW METHODS:
      Studies were included if PTH was obtained within 24 hours of thyroidectomy.
      Studies were excluded (1) if only a hemithyroidectomy was performed, (2) if means
      of studied PTH values were not reported in the article, or (3) if the time of the
      PTH draw fell outside of defined "intraoperative" or "early postoperative"
      windows. PTH values were divided into 3 groups: preoperative (control group),
      intraoperative (ie, discharge decisions were based on PTH values drawn in the
      operating room), and early postoperative (ie, PTH values at 1 to 4 hours after
      surgery were used as a guide). RESULTS: The reported means of perioperative PTH
      levels and percentage of patients who developed hypocalcemia were collected from
      14 studies. PTH evaluated at both the intraoperative and early postoperative
      periods was significantly lower in patients who became hypocalcemic versus
      patients who remained normocalcemic. There was no significant difference when PTH
      was measured intraoperatively or early postoperatively. CONCLUSION:
      Intraoperative PTH has no significant disadvantage versus early postoperative PTH
      when used as a clinical guide for discharge after thyroidectomy.

PMID- 26209078
TI  - Incidence and Risk Factors of Velopharyngeal Insufficiency
      Postadenotonsillectomy.
AB  - OBJECTIVES: To evaluate the incidence and risk factors of velopharyngeal
      insufficiency (VPI) postadenoidectomy, posttonsillectomy, and
      postadenotonsillectomy. STUDY DESIGN: Retrospective chart review. SETTING:
      Academic tertiary care center (2007-2014). SUBJECTS AND METHODS: Retrospective
      review of patients who underwent adenoidectomies, tonsillectomies, or
      adenotonsillectomies by 1 pediatric otolaryngologist. Patient's age, sex, type of
      surgery, indication for surgery, medical syndromes, tonsil grade, adenoid size,
      and pre- and postoperative nasal air emissions were obtained. RESULTS: The VPI
      risk at 3 weeks postoperatively was 13.6% (95% CI: 9.0%, 18.2%) for
      adenotonsillectomies, 3.2% (95% CI: 1.2%, 7.6%) for adenoidectomies, and 2.2%
      (95% CI: 2.1%, 6.5%) for tonsillectomies. There was a significantly higher risk
      of VPI with combined procedures in comparison with adenoidectomies (P = .02) or
      tonsillectomies alone (P = .03). There was no significant difference in risk of
      VPI between adenoidectomies and tonsillectomies (P = .78); between surgical
      indication groups (sleep-disordered breathing vs other; P = .15); or in terms of
      sex (P = .80), age (P = .11), tonsil grade (P = .96), or adenoid size (P = .15).
      There was no qualitative difference in postoperative nasal air emissions between
      patients with and without medical syndromes. CONCLUSION: Our data are consistent
      with the literature that most VPI after adenotonsillectomy is temporary in nature
      and resolves by 5 months postoperatively. Combined procedures were shown to have
      a significantly higher risk of VPI. Our rates of VPI were much higher than that
      previously cited and may be indicative of subclinical cases of VPI, which were
      accounted for due to this study's unique methodology.

PMID- 26209079
TI  - Diminished quality of life in non-cardiac chest pain: A cause as much as an
      effect.

PMID- 26209080
TI  - Mining for novel tumor suppressor genes using a shortest path approach.
AB  - Cancer, being among the most serious diseases, causes many deaths every year.
      Many investigators have devoted themselves to designing effective treatments for
      this disease. Cancer always involves abnormal cell growth with the potential to
      invade or spread to other parts of the body. In contrast, tumor suppressor genes
      (TSGs) act as guardians to prevent a disordered cell cycle and genomic
      instability in normal cells. Studies on TSGs can assist in the design of
      effective treatments against cancer. In this study, we propose a computational
      method to discover potential TSGs. Based on the known TSGs, a number of candidate
      genes were selected by applying the shortest path approach in a weighted graph
      that was constructed using protein-protein interaction network. The analysis of
      selected genes shows that some of them are new TSGs recently reported in the
      literature, while others may be novel TSGs. 

PMID- 26209081
TI  - Wnt3a Mediates the Inhibitory Effect of Hyperoxia on the Transdifferentiation of
      AECIIs to AECIs.
AB  - The aim of this study is to investigate the effect of Wnt3a in the
      transdifferentiation of type II alveolar epithelial cells (AECIIs) to type I
      alveolar epithelial cells (AECIs) under hyperoxia condition. In the in vivo
      study, preterm rats were exposed in hyperoxia for 21 days. In the in vitro study,
      primary rat AECIIs were subjected to a hyperoxia and normoxia exposure
      alternatively every 24 hr for 7 days. siRNA-mediated knockout of Wnt3a and
      exogenous Wnt3a were used to investigate the effect of Wnt3a on
      transdifferentiation of AECIIs to AECIs. Wnt5a-overexpressed AECIIs were also
      used to investigate whether Wnt3a could counteract the effect of Wnt5a. The
      results showed that hyperoxia induced alveolar damage in the lung of preterm born
      rats, as well as an increased expression of Wnt3a and nuclear accumulation of
      beta-catenin. In addition, Wnt3a/beta-catenin signaling was activated in isolated
      AECIIs after hyperoxia exposure. Wnt3a knockout blocked the inhibition of the
      transdifferentiation induced by hyperoxia, and Wnt3a addition exacerbated this
      inhibition. Furthermore, Wnt3a addition blocked the transdifferentiation
      promoting effect of Wnt5a in hyperoxia-exposed Wnt5a-overexpressed AECIIs. In
      conclusion, our results demonstrate that the activated Wnt3a/beta-catenin signal
      may be involved in the hyperoxia-induced inhibition of AECIIs'
      transdifferentiation to AECIs.

PMID- 26209082
TI  - Epitope recognition in the human-pig comparison model on fixed and embedded
      material.
AB  - The conditions and the specificity by which an antibody binds to its target
      protein in routinely fixed and embedded tissues are unknown. Direct methods, such
      as staining in a knock-out animal or in vitro peptide scanning of the epitope,
      are costly and impractical. We aimed to elucidate antibody specificity and
      binding conditions using tissue staining and public genomic and immunological
      databases by comparing human and pig-the farmed mammal evolutionarily closest to
      humans besides apes. We used a database of 146 anti-human antibodies and found
      that antibodies tolerate partially conserved amino acid substitutions but not
      changes in target accessibility, as defined by epitope prediction algorithms.
      Some epitopes are sensitive to fixation and embedding in a species-specific
      fashion. We also find that half of the antibodies stain porcine tissue epitopes
      that have 60% to 100% similarity to human tissue at the amino acid sequence
      level. The reason why the remaining antibodies fail to stain the tissues remains
      elusive. Because of its similarity with the human, pig tissue offers a convenient
      tissue for quality control in immunohistochemistry, within and across
      laboratories, and an interesting model to investigate antibody specificity.

PMID- 26209083
TI  - Review of matrix-assisted laser desorption ionization-imaging mass spectrometry
      for lipid biochemical histopathology.
AB  - Matrix-Assisted Laser Desorption Ionization-Imaging Mass Spectrometry (MALDI-IMS)
      is a rapidly evolving method used for the in situ visualization and localization
      of molecules such as drugs, lipids, peptides, and proteins in tissue sections.
      Therefore, molecules such as lipids, for which antibodies and other convenient
      detection reagents do not exist, can be detected, quantified, and correlated with
      histopathology and disease mechanisms. Furthermore, MALDI-IMS has the potential
      to enhance our understanding of disease pathogenesis through the use of
      "biochemical histopathology". Herein, we review the underlying concepts, basic
      methods, and practical applications of MALDI-IMS, including post-processing steps
      such as data analysis and identification of molecules. The potential utility of
      MALDI-IMS as a companion diagnostic aid for lipid-related pathological states is
      discussed.

PMID- 26209085
TI  - Biomechanical behavior of valgus foot in children with cerebral palsy: A
      comparative study.
AB  - Valgus foot (VF) is the most common foot deformity in children with cerebral
      palsy (CP), which seriously affects the foot balance in standing and posture
      control in walking. Little information about the locus and stress of internal
      bones was available. To accurately describe the biomechanical behavior of the
      internal bones of VF in CP, we compared the locus and stress of internal bones
      between the normal foot (NF) and VF by finite element models. Compared with the
      NF, displacement of the talus and navicular drop in VF increased by 109% and 171%
      in vertical direction respectively, and the locus of talus had a tendency to
      clockwise rotation and downward movement in coronal plane. In addition, the
      abduction angle of forefoot in VF increased up to 10.3 degrees , which was twice
      more than that in the NF. Moreover, the lateral metatarsophalangeal joints were
      upward tilted 6.3 degrees  comparing with touchdown posture of NF, and peak von
      Mises stress of the internal bones in VF model concentrated on the fourth
      metatarsal. The simulation showed that locus of the forefoot, downward rotation
      of talus head and navicular drop were meaningful to quantify the collapse of
      medial longitudinal arch. It would provide some suggestions to the rehabilitation
      treatments of the CP children's VF.

PMID- 26209084
TI  - The region-dependent biomechanical and biochemical properties of bovine
      cartilaginous endplate.
AB  - Regional biomechanical and biochemical properties of bovine cartilaginous
      endplate (CEP) and its role in disc mechanics and nutrition were determined. The
      equilibrium aggregate modulus and hydraulic permeability between the central and
      lateral regions were examined by confined compression testing. Biochemical assays
      were conducted to quantify the amount of water, collagen, and glycosaminoglycan
      (GAG). The equilibrium aggregate modulus of the CEP in the central region (0.23
      +/- 0.15 MPa) was significantly lower than for the lateral region (0.83 +/- 0. 26
      MPa). No significant regional difference was found for the permeability of the
      CEP (central region: 0.13 +/- 0.07*10(-15)m(4)/Ns and lateral region: 0.09 +/-
      0.03 * 10(-15)m(4)/Ns). CEPs were an average of 75.6% water by wet weight, 41.1%
      collagen, and 20.4% GAG by dry weight in the central region, as well as an
      average of 70.2% water by wet weight, 73.8% collagen, and 11.7% GAG by dry weight
      in the lateral region. Regional differences observed for the equilibrium
      aggregate modulus were likely due to the regional variation in biochemical
      composition. The lateral bovine endplate is much stiffer and may share a greater
      portion of the load. Compared with the nucleus pulposus (NP) and annulus fibrosus
      (AF), a smaller hydraulic permeability was found for the CEP in both the central
      and lateral regions, which could be due to its lower water content and higher
      collagen content. Our results suggest that the CEP may block rapid fluid exchange
      and solute convection, allow pressurization of the interstitial fluid, and play a
      significant role in nutrient supply in response to loading.

PMID- 26209086
TI  - Role of arm motion in feet-in-place balance recovery.
AB  - Although considerable arm movements have been observed at loss of balance,
      research on standing balance focused primarily on the ankle and hip strategies.
      This study aimed to investigate the effect of arm motion on feet-in-place balance
      recovery. Participants stood on a single force plate and leaned forward with a
      straight body posture. They were then released from three forward-lean angles and
      regained balance without moving their forefeet under arm-swing (AS) and arm
      constrained (AC) conditions. Higher success rates and shorter recovery times were
      found with arm motion under moderate balance perturbations. Recovery time was
      significantly correlated with peak linear momentum of the arms. Circumduction arm
      motion caused initial shoulder extension (backward arm movement) to generate
      reaction forces to pull the body forward, but later forward linear momentum of
      the arms helped move the whole body backward to avoid forward falling. However,
      greater lean angles increased difficulty in balance recovery, making the
      influences of the arms less significant. Since arm motions were observed in all
      participants with significantly enhanced performance under moderate balance
      perturbation, it was concluded that moving the arms should also be considered
      (together with the ankles and hips) as an effective strategy for balance
      recovery. 

PMID- 26209087
TI  - An inertial sensor-based system for spatio-temporal analysis in classic cross
      country skiing diagonal technique.
AB  - The present study proposes a method based on ski fixed inertial sensors to
      automatically compute spatio-temporal parameters (phase durations, cycle speed
      and cycle length) for the diagonal stride in classical cross-country skiing. The
      proposed system was validated against a marker-based motion capture system during
      indoor treadmill skiing. Skiing movement of 10 junior to world-cup athletes was
      measured for four different conditions. The accuracy (i.e. median error) and
      precision (i.e. interquartile range of error) of the system was below 6 ms for
      cycle duration and ski thrust duration and below 35 ms for pole push duration.
      Cycle speed precision (accuracy) was below 0.1m/s (0.00 5m/s) and cycle length
      precision (accuracy) was below 0.15m (0.005 m). The system was sensitive to
      changes of conditions and was accurate enough to detect significant differences
      reported in previous studies. Since capture volume is not limited and setup is
      simple, the system would be well suited for outdoor measurements on snow.

PMID- 26209088
TI  - The problem of multimodal concurrent serial order in behavior.
AB  - The "problem of serial order in behavior," as formulated and discussed by Lashley
      (1951), is arguably more pervasive and more profound both than originally stated
      and than currently appreciated. We spell out two complementary aspects of what we
      term the generalized problem of behavior: (i) multimodality, stemming from the
      disparate nature of the sensorimotor variables and processes that underlie
      behavior, and (ii) concurrency, which reflects the parallel unfolding in time of
      these processes and of their asynchronous interactions. We illustrate these on a
      number of examples, with a special focus on language, briefly survey the
      computational approaches to multimodal concurrency, offer some hypotheses
      regarding the manner in which brains address it, and discuss some of the broader
      implications of these as yet unresolved issues for cognitive science. 

PMID- 26209089
TI  - Role of pelvic floor in lower urinary tract function.
AB  - The pelvic floor plays an integral part in lower urinary tract storage and
      evacuation. Normal urine storage necessitates that continence be maintained with
      normal urethral closure and urethral support. The endopelvic fascia of the
      anterior vaginal wall, its connections to the arcus tendineous fascia pelvis
      (ATFP), and the medial portion of the levator ani muscles must remain intact to
      provide normal urethral support. Thus, normal pelvic floor function is required
      for urine storage. Normal urine evacuation involves a series of coordinated
      events, the first of which involves complete relaxation of the external urethral
      sphincter and levator ani muscles. Acquired dysfunction of these muscles will
      initially result in sensory urgency and detrusor overactivity; however, with time
      the acquired voiding dysfunction can result in intermittent urine flow and
      incomplete bladder emptying, progressing to urinary retention in severe cases.
      This review will start with a discussion of normal pelvic floor anatomy and
      function. Next various injuries to the pelvic floor will be reviewed. The
      dysfunctional pelvic floor will be covered subsequently, with a focus on levator
      ani spasticity and stress urinary incontinence (SUI). Finally, future research
      directions of the interaction between the pelvic floor and lower urinary tract
      function will be discussed.

PMID- 26209092
TI  - 60 YEARS OF NEUROENDOCRINOLOGY: Celebrating the brain's other output-input system
      and the monograph that defined neuroendocrinology.
AB  - The brain's unimaginably complex operations are expressed in just two types of
      output: muscle activity and hormone release. These are the means by which the
      brain acts beyond its bony casing. Muscle-mediated actions (such as speaking,
      writing, pupillary reflexes) send signals to the outside world that may convey
      thoughts, emotions or evidence of neurological disorder. The outputs of the brain
      as a hormone secreting gland are usually less evident. Their discovery required
      several paradigm shifts in our understanding of anatomy. The first occurred in
      1655. Exactly 300 years later, Geoffrey Harris' monograph Neural control of the
      pituitary gland launched the scientific discipline that is now known as
      neuroendocrinology. His hypotheses have stood the test of time to a remarkable
      degree. A key part of his vision concerned the two-way 'interplay between the
      central nervous system and endocrine glands'. Over the past 60 years, the
      importance of this reciprocity and the degree to which cerebral functions are
      influenced by the endocrine environment have become increasingly clear. 

PMID- 26209090
TI  - Vitamin D and prostate cancer prognosis: a Mendelian randomization study.
AB  - PURPOSE: Decreased vitamin D levels have been associated with prostate cancer,
      but it is unclear whether this association is causal. A functional single
      nucleotide polymorphism (SNP) in the group-specific component (GC) gene (T > G,
      rs2282679) has been associated with 25-hydroxy (25-OH) vitamin D and 1.25
      dihydroxy (1.25-OH2) vitamin D levels. METHODS: To examine the hypothesized
      inverse relationship between vitamin D status and prostate cancer, we studied the
      association between this SNP and prostate cancer outcome in the prospective
      PROCAGENE study comprising 702 prostate cancer patients with a median follow-up
      of 82 months. RESULTS: GC rs2282679 genotypes were not associated with
      biochemical recurrence [hazard ratios (HR) 0.91, 95 % confidence interval (CI)
      0.73-1.12; p = 0.36], development of metastases (HR 1.20, 95 % CI 0.88-1.63; p =
      0.25) or overall survival (HR 1.10; 95 % CI 0.84-1.43; p = 0.50). CONCLUSIONS: A
      causal role of vitamin D status, as reflected by GC rs2282679 genotype, in
      disease progression and mortality in prostate cancer patients is unlikely.

PMID- 26209093
TI  - 60 YEARS OF NEUROENDOCRINOLOGY: MEMOIR: working in the 'Huts' with the professor:
      the first Maudsley years.

PMID- 26209091
TI  - Epidermal growth factor receptor pathway mutation and expression profiles in
      cervical squamous cell carcinoma: therapeutic implications.
AB  - BACKGROUND: Cervical squamous cell carcinoma (CSCC) is a major cause of female
      mortality worldwide. This study has examined epidermal growth factor receptor
      (EGFR) pathway markers that represent actionable pharmacological targets.
      METHODS: HPV16 positive CSCCs (n = 105 patients) from Madhya Pradesh, India were
      screened for KRAS and PIK3CA mutations by PNA-clamp real-time PCR.
      Immunohistochemistry (IHC) was performed for EGFR, PIK3CA, PTEN, phospho-AKT,
      phospho-mTOR and phospho-44/42 MAPK (ERK1/2). RESULTS: KRAS mutations were
      detected in 0/91 (0%) and PIK3CA mutations in 19/95 (20.0%) informative
      specimens: exon 9, E542 (n = 3) and E545 (n = 15); exon 20, H1047R (n = 1).
      PIK3CA mutation detection was associated with older mean patient age [48.2 vs.
      56.6 years (P = 0.007)] and with post-menopausal age: 5/45 (11.1%) patients <50
      years vs. 14/50 (28.0%) patients >=50 years (P = 0.045; OR = 3.11). EGFR
      expression was present in 60/101 (59.4%) CSCCs and was associated with PIK3CA
      mutation detection (P < 0.05) but not age (P > 0.05). EGFR and phospho-AKT
      staining showed associations with tumor grade and/or lymph node status (P <
      0.05). Significant associations were not found for the other study markers (P >
      0.05). CONCLUSION: These data show that PIK3CA mutation acquisition is related to
      patient age and EGFR expression. The absence of KRAS mutations supports the
      potential of anti-EGFR therapies for CSCC treatment. The relatively high PIK3CA
      mutation rates indicate that PI3K may be a therapeutic target for a significant
      subset of CSCC patients. Qualitatively distinct IHC staining profiles for the
      marker panel were noted patient to patient; however, across patients, consistent
      linear relationships between up- and downstream pathway markers were not
      observed. Evaluation of the expression status of potential cancer pathway targets
      may be of value in addition to molecular profiling for choosing among therapeutic
      options.

PMID- 26209095
TI  - Baby Factories in Nigeria: Starting the Discussion Toward a National Prevention
      Policy.
AB  - Baby factories and baby harvesting are relatively new terms that involve
      breeding, trafficking, and abuse of infants and their biological mothers. Since
      it was first described in a United Nations Educational, Scientific and Cultural
      Organization report in Nigeria in 2006, several more baby factories have been
      discovered over the years. Infertile women are noted to be major patrons of these
      baby factories due to the stigmatization of childless couples in Southern Nigeria
      and issues around cultural acceptability of surrogacy and adoption. These
      practices have contributed to the growth in the industry which results in
      physical, psychological, and sexual violence to the victims. Tackling baby
      factories will involve a multifaceted approach that includes advocacy and
      enacting of legislation barring baby factories and infant trafficking and harsh
      consequences for their patrons. Also, programs to educate young girls on
      preventing unwanted pregnancies are needed. Methods of improving awareness and
      acceptability of adoption and surrogacy and reducing the administrative and legal
      bottlenecks associated with these options for infertile couples should be
      explored to diminish the importance of baby factories.

PMID- 26209094
TI  - Comparison of terminally ill cancer- vs. non-cancer patients in specialized
      palliative home care in Germany - a single service analysis.
AB  - BACKGROUND: Palliative care (PC) is no longer offered with preference to cancer
      patients (CA), but also to patients with non-malignant, progressive diseases.
      Taking current death statistics into account, PC in Europe will face a growing
      number of patients dying from non-cancer diseases (NCA). More insights into
      specialized palliative home care (SPHC) in NCAs are needed. METHODS:
      Retrospective analysis and group comparisons between CAs and NCAs of anonymous
      data of all patients cared for between December 2009 and June 2012 by one SPHC
      team in Germany. Patient-, disease- and care-related data are documented in
      clinical routine by specialized PC physicians and nurses in the Information
      System Palliative Care 3.0 (r) (ISPC(r)). RESULTS: Overall, 502 patients were
      cared for by the SPHC team; from 387 patients comprehensive data sets were
      documented. These 387 data sets (CA: N = 300, 77.5 % and NCA: N = 87, 22.5 %) are
      used for further analysis here. NCAs were significantly older (81 vs. 73 years; p
      < .001), than CAs and most often suffered from diseases of the nervous system (40
      %). They needed significantly more assistance with defecation (87 vs. 74 %; p <
      .001) and urination (47 vs. 29 %; p < .001) and were more often affected from
      impaired vigilance (30 vs. 11 %; p < .001) than CAs. A by trend higher proportion
      of NCAs died within one day after admission to palliative home care (12 vs. 5 %;
      p < .05) and a smaller proportion was re-admitted to hospital during home care (6
      vs. 20 %; p < .001). NCAs died predominantly in nursing homes (50 vs. 20 %; p <
      .001). CONCLUSIONS: Although the proportion of NCAs was relatively high in this
      study, the access to PC services seems to takes place late in the disease
      trajectory, as demonstrated by the lower survival rate for NCAs. Nevertheless,
      the results show, that NCAs PC needs are as complex and intense as in CAs.

PMID- 26209096
TI  - Morphometric variability of neuroimaging features in children with agenesis of
      the corpus callosum.
AB  - BACKGROUND: Agenesis of the corpus callosum (ACC) is a developmental brain
      malformation associated with a wide spectrum of structural brain abnormalities
      and genetic loci. To characterize the diverse callosal morphologies and
      malformations of brain development associated with ACC, we report on the
      neuroimaging findings of 201 individuals diagnosed with corpus callosal
      abnormalities. METHODS: We searched through medical records of individuals seen
      at New York Presbyterian Hospital between 2002 and 2013 and thought to have ACC.
      We confirmed 201 individuals meeting criteria and used magnetic resonance imaging
      to characterize morphological variants of the corpus callosum and associated
      brain malformations. RESULTS: The majority of individuals displayed hypoplasia or
      dysplasia of the corpus callosum (N = 160, 80 %). Forty-one (20 %) displayed
      complete agenesis of the corpus callosum with other abnormalities, while only 18
      (9 %) displayed complete agenesis without associated brain abnormalities. White
      matter abnormalities were more frequent in hypoplasia or dysplasia group than
      complete agenesis (28.2 % vs 9.8 %, p < 0.05). In contrast, hippocampal
      abnormalities, colpocephaly, and Probst bundles were significantly more frequent
      in complete agenesis compared to hypoplasia or dysplasia group. CONCLUSIONS:
      Collectively, our results underscore the broad diversity of morphological
      variants of the corpus callosum and associated brain abnormalities in individuals
      with ACC.

PMID- 26209097
TI  - Impairment reduction in older dizzy people in primary care: study protocol for a
      cluster randomised controlled trial.
AB  - BACKGROUND: The management of dizziness in older patients is primarily diagnosis
      oriented. However, in 40% of older patients with dizziness, GPs are not able to
      identify an underlying cause, and a number of common underlying causes of
      dizziness cannot (or hardly) be treated. In this study we will investigate the
      effectiveness of a prognosis-oriented approach in the management of dizziness in
      older patients. This prognosis-oriented approach comprises identification of
      patients at risk for chronic dizziness with persistent impairment by identifying
      risk factors for an unfavourable course of dizziness. Patients at risk for
      chronic dizziness with persistent impairment will be offered treatment addressing
      the identified modifiable risk factors. METHODS/DESIGN: This study will be
      performed in primary care. An intervention study and a validation study will be
      conducted in a three-arm cluster randomised design. In the intervention study we
      will investigate a risk factor guided multi-component intervention. The risk
      factor guided intervention includes: (1) medication adjustment in case of three
      or more prescribed fall-risk-increasing drugs, (2) stepped care in case of
      anxiety disorder and/or depression, and (3) exercise therapy in case of impaired
      functional mobility. The primary outcome measure is dizziness-related impairment,
      which will be assessed with the Dizziness Handicap Inventory. Secondary outcome
      measures are quality of life, anxiety disorder and depression, use of fall-risk
      increasing drugs, dizziness frequency, fall frequency, and healthcare
      utilization. DISCUSSION: This study is, to date, the first study that will
      investigate the effectiveness of a prognosis-oriented approach for reducing
      dizziness-related impairment in older people in primary care. Offering treatment
      that addresses identified modifiable risk factors to patients at high risk for
      chronic dizziness is unique. The pragmatic design of this study will enable
      evaluation of the outcomes in real-life routine practice conditions. An effective
      intervention will not only reduce dizziness-related impairment, but may also
      decrease healthcare utilization and healthcare costs. The previously developed
      risk score that will be validated alongside the intervention study will enable
      GPs to identify patients at high risk for chronic dizziness with persistent
      impairment. TRIAL REGISTRATION: Netherlands Trial Register (identifier: NTR4346),
      registration date 15 December 2013.

PMID- 26209098
TI  - Change in the association of body mass index and systolic blood pressure in
      Germany - national cross-sectional surveys 1998 and 2008-2011.
AB  - BACKGROUND: A recent weakening and even decoupling of the association of body
      mass index (BMI) and systolic blood pressure (SBP) in population data was
      reported, i. a. for Western Europe. METHODS: The association of BMI and SBP in
      recent cross-sectional population data from Germany was investigated in
      participants aged 18-79 years with BMI 17.5-40 kg/m(2) from national health
      examination surveys 1998 (n = 6,931) and 2008-2011 (n = 6,861) in Germany. The
      association was analyzed both in the overall samples and in participants without
      antihypertensive medication. RESULTS: From 1998 to 2008-11, age- and sex
      standardized mean SBP decreased from 129.0 (CI 128.2-129.7) to 124.1 (123.5
      124.6) mmHg in all participants and from 126.0 (125.4-126.7) to 122.3 (121.7
      122.8) mmHg among persons not on antihypertensive medication. The proportion of
      persons treated with antihypertensives augmented from 19.2 % (17.7-20.8) to 25.3
      % (24.0-26.6). Mean BMI remained constant at around 27 kg/m(2) with a slight
      increase in obesity prevalence. BMI was positively associated with SBP both in
      1998 and 2008-11, yet the association tended to level out with increasing BMI
      suggesting a non-linear association. The strength of the BMI-SBP-association
      decreased over time in all and untreated men. In women, the association weakened
      in the overall sample, but remained similarly strong in untreated women. The
      unadjusted linear regression models were used to estimate the increase in SBP
      within 5-unit BMI increases. E. g. for men in 1998, SBP was higher by 7.0 mmHg
      for a BMI increase from 20 to 25 kg/m(2) and by 3.6 mmHg for BMI 30 to 35
      kg/m(2). The corresponding values for 2008-11 were 3.8 mmHg and 1.7 mmHg.
      CONCLUSIONS: The cross-sectional association of BMI and SBP decreased between
      1998 and 2008-11 in Germany, however it did not disappear and it is in part
      explained by improvements in the diagnosis and treatment of high blood pressure.

PMID- 26209099
TI  - Prevalence, antimicrobial susceptibility and virulotyping of Listeria species and
      Listeria monocytogenes isolated from open-air fish markets.
AB  - BACKGROUND: The aim of this study was to investigate the prevalence and
      characterization of Listeria species and Listeria monocytogenes isolated from raw
      fish and open-air fish market environments. Eight hundred and sixty two samples
      including raw fish and fish market environments (samples from workers' hands,
      workers' knives, containers and work surface) were collected from the open-air
      fish markets in the Northern region of Iran. RESULTS: Listeria spp. was isolated
      from 104/488 (21.3%) raw fish and 29/374 (7.8%) of samples from open-air fish
      market environment. The isolates of Listeria spp. included L. innocua (35.3%), L.
      monocytogenes (32.3%), L. seeligeri (18%), and L. ivanovii (14.3%). Of the 43 L.
      monocytogenes isolates, 31 (72.1%), 10 (23.3%) and 2 (4.7%) belonged to serovars
      1/2a, 4b, and 1/2b, respectively. The inlA, inlB, inlC, inlJ, actA, hlyA, iap,
      plcA, and prfA virulence-associated genes were detected in almost all of the L.
      monocytogenes isolates. The Listeria spp. isolates showed high resistance against
      tetracycline (23.3%), penicillin G, and cephalothin (each 16.5%). Besides, we
      observed significant resistance level to tetracycline (27.9%), ampicillin
      (20.9%), cephalothin, penicillin G, and streptomycin (each 16.3%) in the L.
      monocytogenes isolates. All of the isolates were susceptible to cefotaxime,
      gentamicin, kanamycin, and pefloxacin. We found that tetM (25.6%), tetA (23.3%),
      ampC (14%), and penA (11.6%) were the most prevalent antibiotic resistance genes
      in the L. monocytogenes isolates. CONCLUSIONS: Recovery of potentially pathogenic
      L. monocytogenes from raw fish and environment of open-air fish market samples in
      this study is a convincing evidence for the zoonotic potential of listeriosis.

PMID- 26209100
TI  - The microRNA-1246 promotes metastasis in non-small cell lung cancer by targeting
      cytoplasmic polyadenylation element-binding protein 4.
AB  - BACKGROUND: The microRNAs present a class of non-coding RNAs which are usually
      implicated in tumor biology. Recent report has unraveled that a novel member of
      microRNA family called miR-1246. However, the functional role and molecular
      mechanisms of miR-1246 in non-small cell lung cancer (NSCLC) is still elusive.
      METHODS: Using RT-PCR, luciferase reporter, mRNA microarrays, invasion and
      migration assays, we investigated the potential role of miR-1246 in the
      pathogenesis of NSCLC. RESULTS: In this study, we showed that miR-1246 markedly
      promoted NSCLC cell migration and invasion. Meanwhile, we found that cytoplasmic
      polyadenylation element binding protein 4 (CPEB4) might be involved and serve as
      a direct target of miR-1246 in NSCLC. CPEB4 knockdown substantially enhanced
      NSCLC migration and invasion resembling the effect of miR-1246 in NSCLC. CPEB4 is
      also frequently downregulated in NSCLC and decreased CPEB4 expression correlated
      with poor survival. CONCLUSIONS: These results suggested that the miR-1246 may
      promote cell metastasis by targeting CPEB4. Meanwhile, the level of CPEB4 could
      be used as a potential marker in NSCLC patients. Our findings unraveled novel
      functions of miR-1246 in lung cancer cells and shed light on NSCLC prognosis.

PMID- 26209102
TI  - Assessment of dipyridamole stress echocardiography for risk stratification of
      diabetic patients.
AB  - BACKGROUND: Despite advances in medical therapy, cardiovascular disease, mainly
      coronary artery disease (CAD), remains the leading cause of mortality among
      patients with diabetes mellitus (DM). The objective of the present study was to
      assess the effectiveness of dipyridamole stress echocardiography in identify
      diabetic patients at high risk for cardiovascular events. METHODS: Dipyridamole
      stress echocardiography was administered to 483 diabetic patients (294 women;
      mean age 63.41 +/- 11.28 years) between July 2006 and December 2012. RESULTS:
      Follow-up data were available for 264 patients (163 women; mean age 64.3 +/- 10.5
      years): 250 with a negative stress echocardiography and 14 with a positive stress
      echo. During a mean follow-up time of 18 +/- 14 months, a cardiovascular event
      occurred in 18 (6.8%) patients, 12 (4.8%) in patients with a negative stress echo
      (n = 250) during a mean follow-up period of 20 +/- 16 months and 6 (42%) in
      patients with positive stress echo (n = 14) during a mean follow-up of 13 +/- 13
      months. The positive and negative predictive values of stress echocardiography
      were 42% and 96% respectively. The accuracy value was 92%. A Cox regression model
      showed that CAD (hazard ratio [HR] 5.4, 95% confidence interval [CI] 1.9-15.4; p
      = 0.002) and positive stress echocardiography (HR 7.1, 95% CI 2.5-20.5; p <
      0.001) were significant predictors of cardiovascular events. CONCLUSIONS: For
      patients with diabetes, a negative dipyridamole stress echocardiogram predicts
      favorable outcome during the first year of follow-up. A new stress imaging test
      should be done after 12 months in diabetic patients.

PMID- 26209103
TI  - Early biting of the Anopheles gambiae s.s. and its challenges to vector control
      using insecticide treated nets in western Kenya highlands.
AB  - Long term use of insecticides in malaria vector control has been shown to alter
      the behavior of vectors. Such behavioral shifts have the potential of undermining
      the effectiveness of insecticide-based control interventions. The effects of
      insecticide treated nets (ITNs) use on the composition, biting/feeding and
      sporozoite rates of Anopheles gambiae s.l. mosquitoes in Musilongo village,
      Vihiga County of western Kenya highlands were investigated. Adult mosquitoes were
      collected in selected sleeping spaces inside six randomly selected houses using
      miniature Centre for Disease Control and Prevention (CDC) light traps. Mosquito
      sampling in each house was conducted twice every week for 16 consecutive months
      (May 2010-August 2012). At each sampling a single trap was set in the selected
      space inside each house such that it collected mosquitoes alternatively from
      18:00 to 21:00h and 21:00 to 06:00h every week. All collected mosquitoes were
      morphologically identified. Female Anopheles mosquitoes were classified according
      to their physiological status as unfed, fed, partially gravid and gravid, sorted
      and counted. Members of the A. gambiae complex were identified using a Polymerase
      chain reaction (PCR) method. Enzyme-linked-immunosorbent assay (ELISA) was used
      to determine blood meal sources and Plasmodium infection rates in A. gambiae s.l.
      mosquitoes. Blood meal tests were conducted on DNA extracted from gut contents of
      blood fed A. gambiae s.l. The head and thorax section of dried samples of A.
      gambiae s.l. were used in testing for the presence of Plasmodium falciparum (Pf)
      sporozoites. Overall, 735 adult female Anopheles comprising 708 [96.3%] A.
      gambiae s.l. and 27 [3.7%] Anopheles funestus mosquitoes were collected. A.
      gambiae s.l. population collected comprised, 615 [86.9%] unfed and 38 [5.4%] fed
      adult mosquitoes. The rest were either partially or fully gravid. The proportion
      of A. gambiae s.l. biting indoors within 18:00-21:00h was 15.8% (103/653) at a
      rate of 3.2bites per person per hour compared to 84.2% biting from 21:00-06:00h
      at a rate of 3.8 bites/per/h. An estimated 97.7% A. gambiae ss and 2.3% A.
      arabiensis constituted the indoor biting A. gambiae s.l. The population of An.
      gambiae s.l. biting from 18:00 to 21:00h had a Plasmodium faciparum (pf)
      sporozoite rate of 3.8% compared to 3.5% observed in populations biting within
      21:00-06:00h. Human blood constituted 89% of An. gambiae s.l. blood meal sources.
      The risk of malaria transmission from 21:00 to 06:00h was approximately 5 fold
      the risk within 18:00-21:00h. Majority of the infective female A. gambiae s.l.
      adults were biting deep into the night than in the early hours of the night.
      Humans remain the preferred source of blood meal for A. gambiae s.s. the dominant
      malaria vector in the highlands. ITNs remain a fundamental control intervention
      against malaria transmission since female blood seekers were more during bed time
      than pre-bed time. Advocacy on enhanced net availability, integrity and usage in
      Kenyan highlands can reduce Pf transmission. Additional complementary
      interventions are required to control the biting and parasite transmission
      encountered before bed-time.

PMID- 26209101
TI  - Development and multi-centre evaluation of a method for assessing the severity of
      potential harm of medication reconciliation errors at hospital admission in
      elderly.
AB  - BACKGROUND: Medication reconciliation is a powerful process to correct medication
      errors (ME) resulting from miscommunicated information at transitions of care.
      This study aims to develop and evaluate a scoring method for assessing the
      severity of potential harm of ME intercepted by medication reconciliation at
      hospital admission in elderly. METHODS: The development of the scoring method was
      based on a literature search and the creation of a list of high-risk drugs used
      in outpatient care. The evaluation of the method was carried out in 7 French
      hospitals and was based on two criteria: the inter-rater reliability and
      acceptability. The assessment of the inter-rater reliability was based on intra
      class correlation coefficient (ICC) calculations. Each hospital prospectively
      enrolled the 10 first patients aged 65 or older presenting with at least one ME.
      Seven blocks of 10 patients were formed. After randomization, each block was
      rated by practitioners from 3 hospitals. The assessment of the acceptability was
      based on a satisfaction questionnaire. RESULTS: A clinical algorithm was
      developed. The inter-rater reliability of the method was validated by the overall
      agreement of the 7 hospitals ratings. The agreement was at least substantial
      (ICC>0.60) and in most of cases almost perfect (ICC>0.80). The acceptability of
      the method was judged as satisfactory. CONCLUSION: This multi-centre project has
      validated an instrument for assessing the severity of potential harm of ME
      intercepted by medication reconciliation. This will allow studies to be conducted
      with large cohorts of patients in order to develop epidemiological databases of
      ME of potential clinical significance.

PMID- 26209104
TI  - A new species of Simulium (Chirostilbia) (Diptera: Simuliidae) from Mantiqueira
      mountain range, southeastern Brazil.
AB  - Simulium (Chirostilbia) vitribasi n. sp. from the Mantiqueira mountain range, in
      Sao Paulo and Minas Gerais states, southeastern Brazil, is described and
      illustrated based on male, female, pupal and larval morphologies. The pupae of
      the new species is similar to the one of Simulium pertinax Kollar, one of the
      most voracious black fly species in the South and Southeast regions of Brazil and
      a target of control programs in these regions. But the pupa of the new species
      has a large basal fenestra in the gills that distinguishes it from all other S.
      (Chirostilibia) species. The other life stages of the new species also have
      morphological characters that distinguish it from the other species in the
      subgenus: male has scutum black, with patches of thick, golden hairs; female has
      scutum similar to that of the male, without banding or other markers, abdominal
      tergites I and II whitish and sternite VIII dark, heavily sclerotized; anal lobe
      almost as wide as long, with thin, long hairs on its outer margin; larva body
      cuticle has wide scale-like setae, with lobulated distal margins. Females were
      not observed biting humans during the fieldwork.

PMID- 26209105
TI  - Epidemiological characteristics of a new focus of cutaneous leishmaniasis caused
      by Leishmania tropica in Settat, Morocco.
AB  - A new emerging focus of human cutaneous leishmaniasis (HCL) caused by Leishmania
      tropica was identified within the province of Settat. This study was performed in
      order to analyze the reasons of the extension of CL in this area, and to describe
      the clinico-epidemiological characteristic of this emerging focus during 2007
      2012. A total of 553 suspected cases of CL were diagnosed in laboratory of
      Settat, controlled and confirmed in reference national laboratory of
      leishmaniasis in Rabat. Leishmania parasite is found in 356 cases. Most of them
      (33.89%) were recorded in localities of Ouled Ghalem (110 cases) and Laamarcha
      (102 cases) of El Borouj sector. The lesions were typically small, dry and mostly
      located on the face and extremities. Majority of infection (25%) was recorded
      among children under 11 years old, and female (72%). Strains of L. tropica were
      identified by PCR ITS1 from positive slides and zymodeme MON-102 was typed using
      isoenzyme technique on starch gel electrophoresis.

PMID- 26209106
TI  - Multiple dengue virus types harbored by individual mosquitoes.
AB  - The existing knowledge on pathogenesis and aetiology of DHF establishes that
      Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) are caused by two
      subsequent infections of two different serotypes of dengue affecting a common
      human population with a time gap. Present studies have been undertaken on 212
      laboratory reared infected individual mosquitoes from larvae collected from 31
      dengue endemic towns of Rajasthan, India. Type specific DEN viruses were detected
      from individual mosquitoes employing RT-PCR. In 78.7% of 212 infected individual
      mosquitoes studied, vertically transmitted multiple DENV types were observed. We
      report for the first time that single mosquitoes contain multiple dengue virus
      types.

PMID- 26209107
TI  - First detection of Leishmania spp. DNA in Brazilian bats captured strictly in
      urban areas.
AB  - Leishmania spp. is a protozoan that maintains its life cycle in domestic and wild
      animals and it may include bats, a population that has increased in urban
      environments. This study aimed to investigate the presence of Leishmania spp. in
      bats captured strictly in urban areas that are endemic for visceral
      leishmaniasis. The spleen and skin samples of 488 bats from 21 endemic cities in
      northwestern Sao Paulo State, Brazil, were tested for the presence of Leishmania
      kDNA using real-time PCR. Differentiation from Trypanosoma spp. was achieved by
      amplifying a DNA fragment of the ribosomal RNA gene. The presence of Leishmania
      spp. kDNA was verified in 23.9% of bats and Trypanosoma spp. DNA was identified
      in 3.9%. Leishmania species differentiation revealed the presence of Leishmania
      amazonensis in 78.3% of the bats; L. infantum in 17.4%, and 1 sample (4.3%)
      showed a mix pattern of L. infantum and L. amazonensis. We also detected, for the
      first time, L. infantum and L. amazonensis DNA in Desmodus rotundus, the
      hematophagous bat. The presence of Leishmania spp. DNA in bats strictly from
      urban areas endemic for visceral leishmaniasis in the State of Sao Paulo, Brazil
      indicates that these wild and abundant animals are capable of harboring
      Leishmania spp. in this new scenario. Due to their longevity, high dispersion
      capacity and adaptability to synanthropic environments, they may play a role in
      the maintenance of the life cycle of Leishmania parasites.

PMID- 26209108
TI  - Response of a clinical Escherichia coli strain to repeated cefquinome exposure in
      a piglet tissue-cage model.
AB  - BACKGROUND: In order to provide some basis for effective dosage regimens that
      optimize efficacy with respect to bacteriological and clinical cures, the in vivo
      activity of cefquinome against a clinical Escherichia coli (E.coli) strain (the
      minimum inhibitory concentration value for this strain equals to the MIC90 value
      of 0.25 MUg/ml for 210 E.coli strains isolated from pigs) was investigated by
      using a piglet tissue-cage infection model. The aim was to elucidate the
      pharmacokinetic/pharmacodynamics (PK/PD) index associated with cefquinome
      efficacy, and then to identify the magnitude of the PK/PD parameter required for
      different degree of efficacy in clinical treatment. RESULTS: Tissue-cage
      infection model was established in piglets, and then the animals received
      intramuscular injection of cefquinome twice a day for 3 days to create a range of
      different drug exposures. The tissue-cage fluid was collected at 1, 3, 6, 9 and
      12 h after every drug administration for drug concentrationdetermination and
      bacteria counting. Different cefquinome regimens produced different percentages
      of time during that drug concentrations exceeded the MIC (%T > MIC), ranging from
      0% to 100%. Cefquinome administration at 0.2, 0.4, 0.6, 0.8, 1, 2 and 4 mg/kg
      reduced the bacterial count (log10 CFU/mL) in tissue-cage fluid by -1.00 +/-
      0.32, -1.83 +/- 0.08, -2.33 +/- 0.04, -2.96 +/- 0.16, -2.99 +/- 0.16, -2.93 +/-
      0.11, -3.43 +/- 0.18, respectively. The correlation coefficient of the PK/PD
      index with antibacterial effect of the drug was 0.90 for %T > MIC, 0.62 for AUC0
      12/MIC, and 0.61 for Cmax/MIC, suggesting the most important PK/PD parameter was
      %T > MIC. A inhibitory form of sigmoid maximum effect (Emax) model was used to
      estimate %T > MIC, and the respective values required for continuous 1/6-log
      drop, 1/3-log drop and 1/2-log drop of the clinical E.coli count during each 12 h
      treatment period were 3.97%, 17.08% and 52.68%. CONCLUSIONS: The data derived
      from this study showed that cefquinome exhibited time-dependent killing profile.
      And from the results of the present study, it can be assumed that when %T > MIC
      reached 52.68%, cefquinome could be expected to be effective against a clinical
      E.coli strain for which the MIC value is below 0.128 MUg/ml (3-log drop of
      bacteria count can be achieved after six successive administrations for 3 days).

PMID- 26209109
TI  - Low Quality of Free Coaching Apps With Respect to the American College of Sports
      Medicine Guidelines: A Review of Current Mobile Apps.
AB  - BACKGROUND: Low physical activity level is a significant contributor to chronic
      disease, weight dysregulation, and mortality. Nearly 70% of the American
      population is overweight, and 35% is obese. Obesity costs an estimated US$ 147
      billion annually in health care, and as many as 95 million years of life.
      Although poor nutritional habits remain the major culprit, lack of physical
      activity significantly contributes to the obesity epidemic and related lifestyle
      diseases. OBJECTIVE: Over the past 10 years, mobile devices have become
      ubiquitous, and there is an ever-increasing number of mobile apps that are being
      developed to facilitate physical activity, particularly for active people.
      However, no systematic assessment has been performed about their quality with
      respect to following the parameters of sound fitness principles and scientific
      evidence, or suitability for a variety of fitness levels. The aim of this paper
      is to fill this gap and assess the quality of mobile coaching apps on iOS mobile
      devices. METHODS: A set of 30 popular mobile apps pertaining to physical activity
      programming was identified and reviewed on an iPhone device. These apps met the
      inclusion criteria and provided specific prescriptive fitness and exercise
      programming content. The content of these apps was compared against the current
      guidelines and fitness principles established by the American College of Sports
      Medicine (ACSM). A weighted scoring method based on the recommendations of the
      ACSM was developed to generate subscores for quality of programming content for
      aerobic (0-6 scale), resistance (0-6 scale), and flexibility (0-2 scale)
      components using the frequency, intensity, time, and type (FITT) principle. An
      overall score (0-14 scale) was generated from the subscores to represent the
      overall quality of a fitness coaching app. RESULTS: Only 3 apps scored above 50%
      on the aerobic component (mean 0.7514, SD 1.2150, maximum 4.1636), 4 scored above
      50% on the resistance/strength component (mean 1.4525, SD 1.2101, maximum
      4.1094), and no app scored above 50% on the flexibility component (mean 0.1118,
      SD 0.2679, maximum 0.9816). Finally, only 1 app had an overall score (64.3%)
      above 50% (mean 2.3158, SD 1.911, maximum 9.0072). CONCLUSIONS: There are over
      100,000 health-related apps. When looking at popular free apps related to
      physical activity, we observe that very few of them are evidence based, and
      respect the guidelines for aerobic activity, strength/resistance training, and
      flexibility, set forth by the ACSM. Users should exercise caution when adopting a
      new app for physical activity purposes. This study also clearly identifies a gap
      in evidence-based apps that can be used safely and effectively to start a
      physical routine program, develop fitness, and lose weight. App developers have
      an exciting opportunity to improve mobile coaching app quality by addressing
      these gaps.

PMID- 26209110
TI  - beta-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic
      phenotype in breast cancer cells.
AB  - A greater understanding of the molecular basis of breast cancer metastasis will
      lead to identification of novel therapeutic targets and better treatments. Rap1B
      is a small GTPase that suppresses the metastasis of breast cancer cells by
      increasing cell-cell adhesion. In breast cancer, a decrease in Rap1B prenylation
      and subsequent loss of Rap1B at the plasma membrane decreases cell-cell adhesion
      and increases cell scattering, which promotes the metastatic phenotype. Protein
      kinase A (PKA) was recently found to phosphorylate Rap1B and inhibit its
      prenylation. PKA is activated by G protein-coupled receptors (GPCR) that
      stimulate Galphas. In this study, we investigated whether the general Galphas
      activator, cholera toxin, and agonists of the beta-adrenergic receptor (betaAR),
      which is a Galphas-coupled GPCR, promote Rap1B phosphorylation and inhibit its
      prenylation. We show here that cholera toxin and betaAR activation phosphorylate
      Rap1B and inhibit its prenylation and membrane localization, reducing cell-cell
      adhesion and promoting cell scattering. Furthermore, we report that breast cancer
      cell migration is decreased by the FDA-approved beta-blocker, propranolol.
      Pharmacological targeting of GPCRs, especially those such as the betaAR that are
      regulated by FDA-approved drugs, to increase cell adhesion and decrease cell
      scattering could provide a promising therapeutic approach to reduce breast cancer
      metastasis. 

PMID- 26209111
TI  - Wavelet analysis of cardiac optical mapping data.
AB  - BACKGROUND: Optical mapping technology is an important tool to study cardiac
      electrophysiology. Transmembrane fluorescence signals from voltage-dependent dyes
      need to be preprocessed before analysis to improve the signal-to-noise ratio.
      Fourier analysis, based on spectral properties of stationary signals, cannot
      directly provide information on the spectrum changes with respect to time.
      Fourier filtering has the disadvantage of causing degradation of abrupt waveform
      changes such as those in action potential signals. Wavelet analysis has the
      ability to offer simultaneous localization in time and frequency domains,
      suitable for the analysis and reconstruction of irregular, non-stationary signals
      like the fast action-potential upstroke, and better than conventional filters for
      denoising. METHODS: We applied discrete wavelet transformation for temporal
      processing of optical mapping signals and wavelet packet analysis approaches to
      process activation maps from simulated and experimental optical mapping data from
      canine right atrium. We compared the results obtained with the wavelet approach
      to a variety of other methods (Fast Fourier Transformation (FFT) with finite or
      infinite response filtering, and Gaussian filters). RESULTS: Temporal wavelet
      analysis improved signal-to-noise ratio (SNR) better than FFT filtering for 5
      10dB SNR, and caused less distortion of the action potential waveform over the
      full range of simulated noise (5-20dB). Spatial wavelet filtering produced more
      efficient denoising and/or more accurate conduction velocity estimates than
      Gaussian filtering. Propagation patterns were also best revealed by wavelet
      filtering. CONCLUSIONS: Wavelet analysis is a promising tool, facilitating
      accurate action potential characterization, activation map formation, and
      conduction velocity estimation.

PMID- 26209112
TI  - Neurosubstrates and mechanisms underlying the extinction of associative motor
      memory.
AB  - Eyeblink conditioning is one of the most commonly used model systems to
      investigate the neural mechanisms underlying associative motor learning. It is
      well established that the acquisition and retention of conditioned eyeblink
      responses (CRs) involve neural plasticity in both the cerebellar cortex and deep
      cerebellar nuclei (DCN). Nevertheless, how learned CRs are extinguished remains
      relatively unclear. It has been suggested that extinguished CRs can recur
      spontaneously, can reappear by exposure to certain stimuli, and can be reacquired
      in fewer training trials than originally needed, indicating that associative
      motor memory is not merely erased by extinction training. Instead, the motor
      memory is preserved to some degree. Herein, we reviewed recent experimental
      findings demonstrating that the cerebellum subserves the preservation of learned
      CRs. In addition, several lines of evidence have suggested that forebrain
      structures (i.e., the medial prefrontal cortex and hippocampus) are involved in
      the CR extinction. We proposed possible mechanisms related to how preserved motor
      memory in the cerebellum is inhibited by the forebrain structures via the
      amygdalar complex. 

PMID- 26209113
TI  - Usefulness of Cardiac Troponins as Markers of Early Treatment Response in Cardiac
      Sarcoidosis.
AB  - Evaluation and treatment of cardiac sarcoidosis (CS) suffer from lack of
      sensitive and easily repeatable markers of disease activity. We studied
      measurements of high-sensitivity cardiac troponin T or troponin I (hs-cTnT/I)
      taken at presentation and during treatment in 62 patients with new-onset CS (48
      women, mean age 49 years). Hs-cTnT was measured in 50 patients and was elevated
      (>13 ng/L) at presentation in 26 of them (52%). Hs-cTnI was measured in the
      remaining 12 patients and was elevated (>0.04 ng/mL) in 7 of them (58%). Left
      ventricular ejection fraction averaged 43 +/- 14% in association with elevated hs
      cTnT/I (n = 33) versus 53 +/- 10% with normal hs-cTnT/I (n = 29; p = 0.001). Hs
      cTnT/I was remeasured after 4 weeks of steroid therapy in 38 patients and was
      normalized in 16 of the 24 (67%) with an elevated pretreatment concentration and
      remained normal in the rest of the 14 patients (p <0.001). During follow-up
      (median, 17 months), cardiac death (n = 2), aborted sudden death (n = 5),
      sustained ventricular tachycardia (n = 8), or new complete atrioventricular block
      (n = 1) was recorded in 11 of 33 patients with elevated hs-cTnT/I versus in 5 of
      29 with normal hs-cTnT/I (log-rank p = 0.068). Two-year event-free Kaplan-Meier
      cardiac survival estimate (95% confidence interval) was 67% (48% to 81%) with
      elevated hs-cTnT/I versus 93% (76% to 99%) with normal hs-cTnT/I. In CS,
      circulating hs-cTnT/I may help clinicians evaluate disease activity and treatment
      response. Their prognostic value remains tentative pending more follow-up data.

PMID- 26209115
TI  - Electrocardiographic Total 12-Lead QRS Voltage in Patients Having Operative
      Resection of Syphilitic Aortic Aneurysm.
AB  - Electrocardiographic voltage has been used to determine the presence of left
      ventricular hypertrophy for about 70 years. Varying electrocardiographic criteria
      have been applied. We have found total 12-lead QRS voltage to be most useful in
      this regard. We measured total 12-lead QRS voltage in 24 patients in whom an
      ascending aortic aneurysm was resected and histologic study of its wall was
      classic of syphilitic aortitis. In these 24 patients total 12-lead QRS voltage
      ranged from 57 to 161 mm, averaging 120 +/- 32 in the 11 men and 106 +/- 24 mm in
      the 13 women. If normal 12-lead QRS voltage in adults is considered to be >175 mm
      not a single one of the 24 patients had normal voltage. Indeed, most were in the
      low normal area. Thus, this study provides some evidence via this indirect means
      that the heart itself is infrequently involved by syphilitic aortitis which
      produces an ascending aortic aneurysm of sufficient size to warrant resection.

PMID- 26209114
TI  - Clinical Characteristics and Outcome of Alcohol Septal Ablation With Confirmation
      by Nitroglycerin Test for Drug-Refractory Hypertrophic Obstructive Cardiomyopathy
      With Labile Left Ventricular Outflow Obstruction.
AB  - Careful evaluation, including provocation tests, is needed to specify an
      indication for septal reduction therapy in patients with drug-refractory
      hypertrophic obstructive cardiomyopathy. This study aimed to evaluate the outcome
      of alcohol septal ablation (ASA) using an intravenous nitroglycerin test (IV
      NTG). Of consecutive 156 patients, after excluding cases of severe valvular
      disease and repeat septal reduction therapy, we investigated the clinical
      characteristics of patients with labile obstruction (n = 32) and the outcomes
      after ASA using the IV-NTG test; comparisons were made with those exhibiting
      basal obstruction (a resting gradient of >=30 mm Hg). The patients with labile
      obstruction had less left ventricular mass (141 +/- 47 vs 182 +/- 59 g, p =
      0.003) and less brain natriuretic peptide values (414 +/- 576 vs 744 +/- 625
      pg/ml, p <0.001) than those with basal obstruction. Immediately after ASA, the
      gradients improved from 15 +/- 7 to 5 +/- 5 mm Hg and the IV-NTG-provoked
      gradients improved from 74 +/- 25 to 13 +/- 9 mm Hg, respectively. At 1-year
      follow-up, the New York Heart Association functional class had improved from 2.7
      +/- 0.5 to 1.3 +/- 0.5. There was no sudden cardiac death during the follow-up
      period (5.1 +/- 3.0 years), and 8-year survival free from cardiovascular death
      was 94%. In conclusion, patients with labile obstruction had less-severe left
      ventricular hypertrophy but exhibited symptoms comparable to those with basal
      obstruction. The IV-NTG test is a useful method for rapidly confirming acute
      reduction of the latent gradient after the ASA procedure, and the outcome of ASA
      for labile obstruction was favorable.

PMID- 26209116
TI  - Innate and adaptive immunity against Porcine Reproductive and Respiratory
      Syndrome Virus.
AB  - Many highly effective vaccines have been produced against viruses whose virulent
      infection elicits strong and durable protective immunity. In these cases,
      characterization of immune effector mechanisms and identification of protective
      epitopes/immunogens has been informative for the development of successful
      vaccine programs. Diseases in which the immune system does not rapidly clear the
      acute infection and/or convalescent immunity does not provide highly effective
      protection against secondary challenge pose a major hurdle for clinicians and
      scientists. Porcine reproductive and respiratory syndrome virus (PRRSV) falls
      primarily into this category, though not entirely. PRRSV causes a prolonged
      infection, though the host eventually clears the virus. Neutralizing antibodies
      can provide passive protection when present prior to challenge, though infection
      can be controlled in the absence of detectable neutralizing antibodies. In
      addition, primed pigs (through natural exposure or vaccination with a modified
      live vaccine) show some protection against secondary challenge. While peripheral
      PRRSV-specific T cell responses have been examined, their direct contribution to
      antibody-mediated immunity and viral clearance have not been fully elucidated.
      The innate immune response following PRRSV infection, particularly the antiviral
      type I interferon response, is meager, but when provided exogenously, IFN-alpha
      enhances PRRSV immunity and viral control. Overall, the quality of immunity
      induced by natural PRRSV infection is not ideal for informing vaccine development
      programs. The epitopes necessary for protection may be identified through natural
      exposure or modified-live vaccines and subsequently applied to vaccine delivery
      platforms to accelerate induction of protective immunity following vaccination.
      Collectively, further work to identify protective B and T cell epitopes and
      mechanisms by which PRRSV eludes innate immunity will enhance our ability to
      develop more effective methods to control and eliminate PRRS disease. 

PMID- 26209117
TI  - Congenital portosystemic shunts with and without gastrointestinal bleeding - case
      series.
AB  - BACKGROUND: The clinical presentation of congenital portosystemic shunt is
      variable and gastrointestinal bleeding is an uncommon presentation. OBJECTIVE: To
      describe the imaging features of congenital portosystemic shunt as it presented
      in 11 children with (n = 6) and without gastrointestinal bleeding (n = 5).
      MATERIALS AND METHODS: We performed a retrospective study on a clinical and
      imaging dataset of 11 children diagnosed with congenital portosystemic shunt.
      RESULTS: A total of 11 children with congenital portosystemic shunt were included
      in this study, 7 with extrahepatic portosystemic shunts and 4 with intrahepatic
      portosystemic shunts. Six patients with gastrointestinal bleeding had an
      extrahepatic portosystemic shunt, and the imaging results showed that the shunts
      originated from the splenomesenteric junction (n = 5) or splenic vein (n = 1) and
      connected to the internal iliac vein. Among the five cases of congenital
      portosystemic shunt without gastrointestinal bleeding, one case was an
      extrahepatic portosystemic shunt and the other four were intrahepatic
      portosystemic shunts. CONCLUSION: Most congenital portosystemic shunt patients
      with gastrointestinal bleeding had a shunt that drained portal blood into the
      iliac vein via an inferior mesenteric vein. This type of shunt was uncommon, but
      the concomitant rate of gastrointestinal bleeding with this type of shunt was
      high.

PMID- 26209118
TI  - Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell
      disease -- can it differentiate bone infarcts from acute osteomyelitis?
AB  - BACKGROUND: Children with sickle cell disease (SCD) are at risk of bone infarcts
      and acute osteomyelitis. The clinical differentiation between a bone infarct and
      acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR
      images have been proposed as a potential tool to differentiate bone infarcts from
      osteomyelitis. OBJECTIVE: To evaluate the reliability of unenhanced T1-W fat
      saturated MRI for differentiation between bone infarcts and acute osteomyelitis
      in children with SCD. MATERIALS AND METHODS: We retrospectively reviewed the
      records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9
      years) with SCD and acute bone pain who underwent MR imaging including unenhanced
      T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were
      reviewed by a pediatric hematologist with training in infectious diseases to
      determine a clinical standard to define the presence or absence of osteomyelitis.
      A pediatric radiologist reviewed all MR imaging and was blinded to clinical
      information. Based on the signal intensity in T1-W fat-saturated images, the
      children were further classified as positive for osteomyelitis (low bone marrow
      signal intensity) or positive for bone infarct (high bone marrow signal
      intensity). RESULTS: Based on the clinical standard, 5 children were classified
      as positive for osteomyelitis and 26 children as positive for bone infarct
      (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat
      saturated imaging was not significant for the differentiation between bone
      infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging
      parameters on unenhanced MRI proved reliable in differentiating these diagnoses.
      CONCLUSION: The bone marrow signal intensity on unenhanced T1-W fat-saturated MR
      images is not a reliable criterion to differentiate bone infarcts from
      osteomyelitis in children.

PMID- 26209119
TI  - Variation in cervical and breast cancer screening coverage in England: a cross
      sectional analysis to characterise districts with atypical behaviour.
AB  - OBJECTIVES: Reducing cancer screening inequalities in England is a major focus of
      the 2011 Department of Health cancer outcome strategy. Screening coverage
      requires regular monitoring in order to implement targeted interventions where
      coverage is low. This study aimed to characterise districts with atypical
      coverage levels for cervical or breast screening. DESIGN: Observational study of
      district-level coverage in the English Cervical and Breast screening programmes
      in 2012. SETTING: England, UK. PARTICIPANTS: All English women invited to
      participate in the cervical (age group 25-49 and 50-64) and breast (age group 50
      64) screening programmes. OUTCOMES: Risk adjustment models for coverage were
      developed based on district-level characteristics. Funnel plots of adjusted
      coverage were constructed, and atypical districts examined by correlation
      analysis. RESULTS: Variability in coverage was primarily explained by population
      factors, whereas general practice characteristics had little independent effect.
      Deprivation and ethnicity other than white, Asian, black or mixed were
      independently associated with poorer coverage in both screening programmes, with
      ethnicity having the strongest effect; by comparison, the influence of Asian,
      black or mixed ethnic minority was limited. Deprivation, ethnicity and
      urbanisation largely accounted for the lower cervical screening coverage in
      London. However, for breast screening, being located in London remained a strong
      negative predictor. A subset of districts was identified as having atypical
      coverage across programmes. Correlates of deprivation in districts with
      relatively low adjusted coverage were substantially different from overall
      correlates of deprivation. DISCUSSION: These results inform the continuing drive
      to reduce avoidable cancer deaths in England, and encourage implementation of
      targeted interventions in communities residing in districts identified as having
      atypically low coverage. Sequential implementation to monitor the impact of local
      interventions would help accrue evidence on 'what works'.

PMID- 26209120
TI  - A questionnaire survey exploring healthcare professionals' attitudes towards
      teamwork and safety in acute care areas in South Korea.
AB  - OBJECTIVES: Although human factors are important in terms of patient safety,
      there have been very few reports on the attitudes of healthcare professionals
      working in acute care settings in South Korea. In the present study, we
      investigated the attitudes of such professionals, their cultures and their
      management systems. DESIGN: A questionnaire survey with 65 items covering nine
      themes affecting patient safety. Nine themes were compared via a three-or-more
      way analysis of variance, with interaction, followed by multiple comparisons
      among several groups. SETTING: Intensive care units, emergency departments and
      surgical units of nine urban hospitals. PARTICIPANTS: 592 nurses and 160
      physicians. INTERVENTION: None. OUTCOME MEASURES: Mean scores using a five-point
      scale and combined response scores for each of the nine themes. RESULTS: The mean
      score for information-sharing was the highest (3.78+/-0.49) and that for
      confidence/assertion was the lowest (2.97+/-0.34). The mean scores for teamwork,
      error management, work value, organisational climate, leadership, stress and
      fatigue level, and error/procedural compliance were intermediate. Physicians
      showed lower scores in leadership and higher scores in information-sharing than
      nurses. Respondents with 24 months or less of a clinical career showed higher
      scores in leadership, stress and fatigue, and error scores and lower scores in
      work value than more experienced respondents. CONCLUSIONS: Our results suggest
      that medical personnel in Korea are relatively reluctant to disclose error or
      assert their different opinions with others. Many did not adequately recognise
      the negative effects of fatigue and stress, attributed errors to personal
      incompetence, and error-management systems were inadequate. Discrepancies in
      leadership and information-sharing were evident between professional groups, and
      leadership, stress, fatigue level, work value and error scores varied with the
      length of work experience. These can be used as baseline data to establish
      training programmes for patient safety in Korea.

PMID- 26209122
TI  - Implementation and validation of a new fixation system for stereotactic radiation
      therapy: An analysis of patient immobilization.
AB  - PURPOSE: Stereotactic radiation therapy is an established treatment technique for
      intracranial malignancies. We evaluated a new intracranial immobilization system
      with an emphasis on determining the intrafraction motion and the correlation of
      this motion with treatment time. METHODS AND MATERIALS: Patients were immobilized
      using the trUpoint ARCH fixation system (CIVCO Medical Solutions). We collected
      data from 85 lesions in 73 patients treated between November 2011 and December
      2013. Sixty-nine of 73 patients (95%) used the complete mask system; for the
      remaining 4 patients, the system had to be adapted. Patients were treated using
      volumetric modulated arc therapy stereotactic radiation therapy on a TrueBeam
      linear accelerator (Varian Medical Systems, Palo Alto, CA). Fraction doses of 2-8
      Gy were applied in 4-30 fractions. Daily cone beam computed tomography imaging
      was performed before the treatment and was matched to the reference computed
      tomography using a 6-degrees-of-freedom automatching procedure. Additionally,
      posttreatment cone beam computed tomography scans were performed to assess
      intrafraction motion for 67 patients (375 fractions). RESULTS: The average 3
      dimensional setup error was 2.1 +/- 2.9 mm. The mean pitch and roll was -0.1 +/-
      0.7 degrees  and 0.2 +/- 0.7 degrees . A total of 98.0% of the pitch values and
      98.9% of the roll values were <1.5 degrees . Mean intrafractional motion was 0.51
      mm (+/-0.27) and mean treatment time was 10.1 minutes (+/-1.4). The maximum
      intrafractional motion was 2.0 mm in the longitudinal direction; 95% of the total
      shifts were <1.4 mm. The linear regression showed a weak but significant
      influence (R(2) = 0.26, P = .01) of the treatment time on the total
      intrafractional shift. CONCLUSIONS: The new intracranial immobilization system
      appears to be robust in terms of setup accuracy, intrafraction motion, and
      repositioning of the mask system.

PMID- 26209121
TI  - 'Seizure First Aid Training' for people with epilepsy who attend emergency
      departments, and their family and friends: study protocol for intervention
      development and a pilot randomised controlled trial.
AB  - INTRODUCTION: People with chronic epilepsy (PWE) often make costly but clinically
      unnecessary emergency department (ED) visits. Offering them and their carers a
      self-management intervention that improves confidence and ability to manage
      seizures may lead to fewer visits. As no such intervention currently exists, we
      describe a project to develop and pilot one. METHODS AND ANALYSIS: To develop the
      intervention, an existing group-based seizure management course that has been
      offered by the Epilepsy Society within the voluntary sector to a broader audience
      will be adapted. Feedback from PWE, carers and representatives from the main
      groups caring for PWE will help refine the course so that it addresses the needs
      of ED attendees. Its behaviour change potential will also be optimised. A pilot
      randomised controlled trial will then be completed. 80 PWE aged >=16 who have
      visited the ED in the prior 12 months on >=2 occasions, along with one of their
      family members or friends, will be recruited from three NHS EDs. Dyads will be
      randomised to receive the intervention or treatment as usual alone. The proposed
      primary outcome is ED use in the 12 months following randomisation. For the
      pilot, this will be measured using routine hospital data. Secondary outcomes will
      be measured by patients and carers completing questionnaires 3, 6 and 12 months
      postrandomisation. Rates of recruitment, retention and unblinding will be
      calculated, along with the ED event rate in the control group and an estimate of
      the intervention's effect on the outcome measures. ETHICS AND DISSEMINATION:
      Ethical approval: NRES Committee North West-Liverpool East (Reference number
      15/NW/0225). The project's findings will provide robust evidence on the
      acceptability of seizure management training and on the optimal design of a
      future definitive trial. The findings will be published in peer-reviewed journals
      and presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN13 871 327.

PMID- 26209123
TI  - Controlled delivery of a new broad spectrum antibacterial agent against colitis:
      In vitro and in vivo performance.
AB  - Coated pellets and mini-tablets were prepared containing a new broad spectrum
      antibacterial agent: CIN-102, a well-defined, synergistic blend of trans
      cinnamaldehyde, trans-2-methoxycinnamaldehyde, cinnamyl acetate, linalool, beta
      caryophyllene, cineol and benzyl benzoate. The aim was to provide a new treatment
      method for colitis, especially for Inflammatory Bowel Disease (IBD) patients.
      Since the simple oral gavage of CIN-102 was not able to reduce the pathogenic
      bacteria involved in colitis (rat model), the drug was incorporated into
      multiparticulates. The idea was to minimize undesired drug release in the upper
      gastrointestinal tract and to control CIN-102 release in the colon, in order to
      optimize the resulting antibiotic concentration at the site of action. A
      particular challenge was the fact that CIN-102 is a volatile hydrophobic liquid.
      Pellet cores were prepared by extrusion-spheronization and coated with polymer
      blends, which are sensitive to colonic bacterial enzymes. Mini-tablets were
      prepared by direct compression. The release of the main compound of CIN-102
      (cinnamaldehyde, 86.7% w/w) was monitored in vitro. Optimized coated pellets and
      mini-tablets were also tested in vivo: in seven-week-old, male mice suffering
      from dextran sodium sulfate induced colitis. Importantly, both types of
      multiparticulates were able: (i) to significantly reduce the number of luminal
      and mucosal enterobacteria in the mice (the levels of which are increased in the
      disease state), and (ii) to improve the clinical course of the intestinal
      inflammation (decrease in the percentages of mice with bloody stools and
      diarrhea). Thus, the proposed coated pellets and matrix mini-tablets allowing for
      controlled CIN-102 release show a promising potential for new treatment methods
      of colitis. 

PMID- 26209124
TI  - Implementation of transmission NIR as a PAT tool for monitoring drug
      transformation during HME processing.
AB  - The aim of the work reported herein was to implement process analytical
      technology (PAT) tools during hot melt extrusion (HME) in order to obtain a
      better understanding of the relationship between HME processing parameters and
      the extruded formulations. For the first time two in-line NIR probes
      (transmission and reflectance) have been coupled with HME to monitor the
      extrusion of the water insoluble drug indomethacin (IND) in the presence of
      Soluplus (SOL) or Kollidon VA64 hydrophilic polymers. In-line extrusion
      monitoring of sheets, produced via a specially designed die, was conducted at
      various drug/polymer ratios and processing parameters. Characterisation of the
      extruded transparent sheets was also undertaken by using DSC, XRPD and Raman
      mapping. Analysis of the experimental findings revealed the production of
      molecular solutions where IND is homogeneously blended (ascertained by Raman
      mapping) in the polymer matrices, as it acts as a plasticizer for both
      hydrophilic polymers. PCA analysis of the recorded NIR signals showed that the
      screw speed used in HME affects the recorded spectra but not the homogeneity of
      the embedded drug in the polymer sheets. The IND/VA64 and IND/SOL extruded sheets
      displayed rapid dissolution rates with 80% and 30% of the IND being released,
      respectively within the first 20min. 

PMID- 26209125
TI  - Heterocyclic amine-modified polyethylenimine as gene carriers for transfection of
      mammalian cells.
AB  - Branched polyethylenimine (PEI) is extensively used as a polycationic non-viral
      vector for gene delivery. Polyplexes formed with PEI are believed to be released
      from endocytotic vesicles by the osmotic burst mechanism in the rate-limiting
      step in transfection. Increasing the buffering capacity of PEI derivatives in the
      endosomal pH range of 4.5-7.5 should enhance transfection efficiency. In this
      study, PEI was derivatized by covalently attaching heterocyclic amine moieties
      (piperazine, pyridine and imidazole rings with pKa values from 5.23 to 6.04)
      through amide bonds. PEI derivatives with 50% of the primary amines on PEI
      exhibited increased buffering capacity, increased transfection activity and
      decreased cytotoxicity in murine neuroblastoma (Neuro-2a) cells. The relative
      effectiveness in enhancing transfection efficiency was
      piperazine>pyridine>histidine, but each type of amine was the most effective
      under a particular set of conditions. Modified vectors could significantly
      improve transfection efficiency in murine mesenchymal stem cells. PEI25
      derivatized at 50% with histidine administered as polyplexes in the tail veins of
      mice resulted in remarkably enhanced luciferase gene expression in the expected
      organ distribution and much lower toxicity than underivatized PEI25. 

PMID- 26209126
TI  - Histopathology and contaminant concentrations in fish from Kuwait's marine
      environment.
AB  - Kuwait has witnessed major socioeconomic and industrial development in recent
      decades. Consequently, a variety of contaminants related to these activities have
      been discharged directly into the marine environment. This paper describes the
      application of a histopathology baseline survey in two potential sentinel
      species, the Giant sea catfish (Arius thalassinus) and the Fourlined terapon
      (Pelates quadrilineatus) to assess the health of biota inhabiting Kuwait's marine
      environment. Histological analysis revealed several lesion types in both species,
      although the prevalence was generally considered low with no discernible
      differences between sampling locations. The analysis of contaminant burdens
      (metals, PCBs, PBDEs, HBCDD) in A. thalassinus, along with the analysis of bile
      for PAH metabolites in both species, indicated that levels of contaminant
      exposure was low. Overall the data show that both species appear to be
      susceptible to pathologies associated with environmental contaminants and
      therefore suitable for further investigation as sentinel organisms for biological
      effects monitoring. 

PMID- 26209127
TI  - Bioaccumulation and biomagnification of halogenated organic pollutants in
      mangrove biota from the Pearl River Estuary, South China.
AB  - Four biota species were collected from mangrove ecosystems of the Pearl River
      Estuary to investigate the bioaccumulation and biomagnification of
      polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT),
      polybrominated diphenyl ethers (PBDEs), dechlorane plus (DP), and
      decabromodiphenyl ethane (DBDPE). Concentrations of SigmaPCBs, SigmaDDTs,
      SigmaPBDEs, DP, DBDPE and anti-Cl11-DP (the dechlorination product of anti-DP) in
      mangrove biota ranged from 32.1-466, 153-3819, 3.88-59.8, 0.18-6.88, not detected
      (nd)-30.6 and nd-2.65 ng/g lipid weight, respectively. Daggertooth pike conger
      (Muraenesox cinereus) had higher concentrations of contaminants than the other
      three biota species. Significant positive relationship between anti-Cl11-DP and
      anti-DP levels was observed in mangrove biota. DDTs were the predominant HOPs in
      all biota species, followed by PCBs and PBDEs. All the target compounds exhibited
      biomagnification, with biomagnification factors greater than 1 in the studied
      feeding relationships. Food web magnification was found for SigmaPCBs, SigmaDDTs,
      SigmaPBDEs and DP, with trophic magnification factors of 2.76, 2.61, 2.20 and
      2.31, respectively.

PMID- 26209128
TI  - Distributions, sources and ecological risk assessment of arsenic and mercury in
      the surface sediments of the southwestern coastal Laizhou Bay, Bohai Sea.
AB  - The spatial distributions of As and Hg in riverine and marine surface sediments
      of the coastal southwestern Laizhou Bay were obtained, and multiple indices and
      guidelines were applied to assess their contamination and ecological risks. The
      As concentrations in riverine sediments were close to those in marine sediments,
      and on the whole the dominant proportion of As was identified to be from natural
      sources. The Hg concentrations in riverine sediments were much higher than those
      in marine sediments, so river transportation was likely the main way of Hg into
      the southwestern Laizhou Bay. In respect of As, the sediment quality was fine
      according to the risk assessment methods used; in contrast, Hg presented an
      extremely contaminated status with a very high ecological risk in some riverine
      sediments, while most of the marine sediments were relatively much less polluted
      by Hg and under a lower ecological risk from it. 

PMID- 26209129
TI  - Extraction and analysis of the width, gray scale and radian in Chinese signature
      handwriting.
AB  - Forensic handwriting examination is a relevant identification process in forensic
      science. This research obtained ideas from the process of features detection and
      analysis in forensic handwriting examination. A Chinese signature database was
      developed and comprised original signatures, freehand imitation forgeries, random
      forgeries and tracing imitation forgeries. The features of width, gray scale and
      radian combined with stroke orders were automatically extracted after image
      processing. A correlation coefficient was used to precisely characterize and
      express the similarities between signatures. To validate the differences between
      writers, a multivariate analysis of the variance was employed. The canonical
      discriminant analysis was performed between the original and non-original
      signatures; the cross-validation estimated the discriminating power of the width,
      gray scale and radian data. It is suggested that the extraction and analysis of
      these properties in Chinese signatures is reasonable. Meanwhile, forensic
      handwriting examination using the quantitative feature extraction and statistical
      analysis methods in this research could be performed with a satisfactory result
      in the discriminant analysis. 

PMID- 26209130
TI  - Altered expression and editing of miRNA-100 regulates iTreg differentiation.
AB  - RNA editing of miRNAs, especially in the seed region, adds another layer to miRNA
      mediated gene regulation which can modify its targets, altering cellular
      signaling involved in important processes such as differentiation. In this study,
      we have explored the role of miRNA editing in CD4(+) T cell differentiation.
      CD4(+) T cells are an integral component of the adaptive immune system. Naive
      CD4(+) T cells, on encountering an antigen, get differentiated either into
      inflammatory subtypes like Th1, Th2 or Th17, or into immunosuppressive subtype
      Treg, depending on the cytokine milieu. We found C-to-U editing at fifth position
      of mature miR-100, specifically in Treg. The C-to-U editing of miR-100 is
      functionally associated with at least one biologically relevant target change,
      from MTOR to SMAD2. Treg cell polarization by TGFbeta1 was reduced by both edited
      and unedited miR-100 mimics, but percentage of Treg in PBMCs was only reduced by
      edited miR-100 mimics, suggesting a model in which de-repression of MTOR due to
      loss of unedited mir-100, promotes tolerogenic signaling, while gain of edited
      miR-100 represses SMAD2, thereby limiting the Treg. Such delicately
      counterbalanced systems are a hallmark of immune plasticity and we propose that
      miR-100 editing is a novel mechanism toward this end. 

PMID- 26209131
TI  - Blocking of targeted microRNAs from next-generation sequencing libraries.
AB  - Highly abundant microRNAs (miRNAs) in small RNA sequencing libraries make it
      difficult to obtain efficient measurements of more lowly expressed species. We
      present a new method that allows for the selective blocking of specific, abundant
      miRNAs during preparation of sequencing libraries. This technique is specific
      with little off-target effects and has no impact on the reproducibility of the
      measurement of non-targeted species. In human plasma samples, we demonstrate that
      blocking of highly abundant hsa-miR-16-5p leads to improved detection of lowly
      expressed miRNAs and more precise measurement of differential expression overall.
      Furthermore, we establish the ability to target a second abundant miRNA and to
      multiplex the blocking of two miRNAs simultaneously. For small RNA sequencing,
      this technique could fill a similar role as do ribosomal or globin removal
      technologies in messenger RNA sequencing. 

PMID- 26209132
TI  - Processing by MRE11 is involved in the sensitivity of subtelomeric regions to DNA
      double-strand breaks.
AB  - The caps on the ends of chromosomes, called telomeres, keep the ends of
      chromosomes from appearing as DNA double-strand breaks (DSBs) and prevent
      chromosome fusion. However, subtelomeric regions are sensitive to DSBs, which in
      normal cells is responsible for ionizing radiation-induced cell senescence and
      protection against oncogene-induced replication stress, but promotes chromosome
      instability in cancer cells that lack cell cycle checkpoints. We have previously
      reported that I-SceI endonuclease-induced DSBs near telomeres in a human cancer
      cell line are much more likely to generate large deletions and gross chromosome
      rearrangements (GCRs) than interstitial DSBs, but found no difference in the
      frequency of I-SceI-induced small deletions at interstitial and subtelomeric
      DSBs. We now show that inhibition of MRE11 3'-5' exonuclease activity with Mirin
      reduces the frequency of large deletions and GCRs at both interstitial and
      subtelomeric DSBs, but has little effect on the frequency of small deletions. We
      conclude that large deletions and GCRs are due to excessive processing of DSBs,
      while most small deletions occur during classical nonhomologous end joining (C
      NHEJ). The sensitivity of subtelomeric regions to DSBs is therefore because they
      are prone to undergo excessive processing, and not because of a deficiency in C
      NHEJ in subtelomeric regions. 

PMID- 26209133
TI  - Transcription yield of fully 2'-modified RNA can be increased by the addition of
      thermostabilizing mutations to T7 RNA polymerase mutants.
AB  - On average, mutations are deleterious to proteins. Mutations conferring new
      function to a protein often come at the expense of protein folding or stability,
      reducing overall activity. Over the years, a panel of T7 RNA polymerases have
      been designed or evolved to accept nucleotides with modified ribose moieties.
      These modified RNAs have proven useful, especially in vivo, but the
      transcriptional yields tend to be quite low. Here we show that mutations
      previously shown to increase the thermal tolerance of T7 RNA polymerase can
      increase the activity of mutants with expanded substrate range. The resulting
      polymerase mutants can be used to generate 2'-O-methyl modified RNA with yields
      much higher than enzymes currently employed.

PMID- 26209134
TI  - The master regulator of IncA/C plasmids is recognized by the Salmonella Genomic
      island SGI1 as a signal for excision and conjugal transfer.
AB  - The genomic island SGI1 and its variants, the important vehicles of multi
      resistance in Salmonella strains, are integrative elements mobilized exclusively
      by the conjugative IncA/C plasmids. Integration and excision of the island are
      carried out by the SGI1-encoded site-specific recombinase Int and the
      recombination directionality factor Xis. Chromosomal integration ensures the
      stable maintenance and vertical transmission of SGI1, while excision is the
      initial step of horizontal transfer, followed by conjugation and integration into
      the recipient. We report here that SGI1 not only exploits the conjugal apparatus
      of the IncA/C plasmids but also utilizes the regulatory mechanisms of the
      conjugation system for the exact timing and activation of excision to ensure
      efficient horizontal transfer. This study demonstrates that the FlhDC-family
      activator AcaCD, which regulates the conjugation machinery of the IncA/C
      plasmids, serves as a signal of helper entry through binding to SGI1 xis promoter
      and activating SGI1 excision. Promoters of int and xis genes have been identified
      and the binding site of the activator has been located by footprinting and
      deletion analyses. We prove that expression of xis is activator-dependent while
      int is constitutively expressed, and this regulatory mechanism is presumably
      responsible for the efficient transfer and stable maintenance of SGI1. 

PMID- 26209136
TI  - Self-Assembly of Ovalbumin Amyloid Pores: Effects on Membrane Permeabilization,
      Dipole Potential, and Bilayer Fluidity.
AB  - Amyloid assembly is inherently a stochastic and a hierarchical process comprising
      the genesis of heterogeneous, transiently populated prefibrillar aggregates that
      are characterized to be non-native oligomeric conformers. These oligomers could
      be either off-pathway or on-pathway species en route to amyloid fibrils that are
      associated with a variety of neurodegenerative disorders, namely, Alzheimer's
      disease, Parkinson's disease, and prion disease, as well as in localized and
      systemic amyloidoses (type II diabetes and dialysis related, respectively).
      Morphological characterizations of these prefibrillar aggregates indicated that
      apparently the doughnut or annular structure is commonly shared among various
      prefibrillar species irrespective of the diverse native structures and
      aggregation mechanisms. In this work, we have elucidated the self-assembly
      mechanism of amyloid pore formation from ovalbumin using a range of biophysical
      techniques that shed light on the time-dependent protein structural changes as
      aggregation progressed. Additionally, on the basis of several pieces of evidence
      suggesting amyloid pore-mediated cytotoxicity, we have investigated the annular
      amyloid-membrane interaction using a comprehensive biophysical approach. The
      influences of annular pores on the intramembrane dipole potential and bilayer
      fluidity, as a consequence of membrane permeabilization, were examined in a
      protein concentration- and time-dependent manner that provided important insights
      into the pore-membrane interactions. Instantaneous membrane permeabilization
      kinetics suggested that plausibly a detergent-like carpet mechanism during
      membrane disruption was effective. Moreover, it was inferred that a loss of
      membrane integrity resulted in the generation of both disordered lipid and
      disoriented water dipoles that reside in the immediate vicinity of the membrane
      bilayer. These key findings may have implications in amyloid-pore-induced
      deleterious effects during amyloid-membrane interactions. 

PMID- 26209137
TI  - Study on viability and chondrogenic differentiation of cryopreserved adipose
      tissue-derived mesenchymal stromal cells for future use in regenerative medicine.
AB  - Adipose-derived mesenchymal stromal cells are promising as a regenerative therapy
      tool for defective tissues in mesenchymal lineage, including fat, bone,
      cartilage, and blood vessels. In potential future clinical applications, adipose
      derived stem cell cryopreservation is an essential fundamental technology. The
      aim of this study is to define an adequate protocol for the cryopreservation of
      adipose-derived mesenchymal stromal cells, by comparing various protocols so as
      to determine the effects of cryopreservation on viability and chondrogenic
      differentiation potential of adipose-derived stem cells upon freeze-thawing of AT
      MSCs colonies cryopreserved with standard and modified protocols, using flow
      cytometry and confocal microscopy. The study concludes that adipose-derived
      mesenchymal stromal cells could be long-term cryopreserved without any loss of
      their proliferative or differentiation potential. 

PMID- 26209138
TI  - Daucosterol inhibits cancer cell proliferation by inducing autophagy through
      reactive oxygen species-dependent manner.
AB  - AIMS: This study aims to evaluate the anti-cancer effect of daucosterol and
      explore its possible mechanism. MAIN METHODS: MTT and colony formation assay were
      performed to determine the effect of daucosterol on cancer cell proliferation in
      vitro. H22 allograft model was used for the assessment of its anti-cancer
      activity in vivo. Intracellular generation of reactive oxygen species (ROS) was
      measured using DCFH-DA probe with flow cytometry system and a laser scanning
      confocal microscope. LC3 (microtubule-associated protein 1 light chain 3)-II
      conversion was monitored with immunofluorescence and immunoblotting to
      demonstrate daucosterol-induced autophagy. KEY FINDINGS: We found that
      daucosterol inhibits the proliferation of human breast cancer cell line MCF-7 and
      gastric cancer cell lines MGC803, BGC823 and AGS in a dose-dependent manner.
      Furthermore, daucosterol inhibits murine hepatoma H22 cell growth in ICR mice.
      Daucosterol treatment induces intracellular ROS generation and autophagy, but not
      apoptotic cell death. Treatment with ROS scavenger GSH (reduced glutathione), NAC
      (N-acetyl-l-cysteine) or autophagy inhibitor 3-Methyladenine (3-MA) counteracted
      daucosterol-induced autophagy and growth inhibition in BGC823 and MCF-7 cancer
      cells. SIGNIFICANCE: Daucosterol inhibits cancer cell proliferation by inducing
      autophagy through ROS-dependent manner and could be potentially developed as an
      anti-cancer agent.

PMID- 26209135
TI  - Post-transcriptional gene silencing triggered by sense transgenes involves
      uncapped antisense RNA and differs from silencing intentionally triggered by
      antisense transgenes.
AB  - Although post-transcriptional gene silencing (PTGS) has been studied for more
      than a decade, there is still a gap in our understanding of how de novo silencing
      is initiated against genetic elements that are not supposed to produce double
      stranded (ds)RNA. Given the pervasive transcription occurring throughout
      eukaryote genomes, we tested the hypothesis that unintended transcription could
      produce antisense (as)RNA molecules that participate to the initiation of PTGS
      triggered by sense transgenes (S-PTGS). Our results reveal a higher level of
      asRNA in Arabidopsis thaliana lines that spontaneously trigger S-PTGS than in
      lines that do not. However, PTGS triggered by antisense transgenes (AS-PTGS)
      differs from S-PTGS. In particular, a hypomorphic ago1 mutation that suppresses S
      PTGS prevents the degradation of asRNA but not sense RNA during AS-PTGS,
      suggesting a different treatment of coding and non-coding RNA by AGO1, likely
      because of AGO1 association to polysomes. Moreover, the intended asRNA produced
      during AS-PTGS is capped whereas the asRNA produced during S-PTGS derives from 3'
      maturation of a read-through transcript and is uncapped. Thus, we propose that
      uncapped asRNA corresponds to the aberrant RNA molecule that is converted to
      dsRNA by RNA-DEPENDENT RNA POLYMERASE 6 in siRNA-bodies to initiate S-PTGS,
      whereas capped asRNA must anneal with sense RNA to produce dsRNA that initiate AS
      PTGS. 

PMID- 26209139
TI  - Selective loss of dopaminergic neurons in the substantia nigra pars compacta
      after systemic administration of MPTP facilitates extinction learning.
AB  - AIMS: Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars
      compacta (SNpc). In PD, thinking and retrieval deficits often arise from
      cognitive impairments. However, the mechanism of cognitive disorders in PD
      remains unknown. Therefore, we investigated cognitive function in PD model mice
      produced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), which specifically destroys the DAergic neurons in the
      SNpc. MAIN METHODS: We evaluated the cognitive function of MPTP-treated mice (PD
      mice) using the contextual fear conditioning test. In the test, each experiment
      consists of three phases: training, re-exposure, and testing. Mice were trained
      with a foot shock (a weak unconditioned stimulus: 1mA/2s duration, once, or an
      intense unconditioned stimulus: 2mA/2s duration, twice), and 24h later, mice were
      re-exposed to the training context for 3min to determine reconsolidation or 30min
      to determine extinction. The percentage of time spent freezing was measured
      during the test session as indexes of memory consolidation, reconsolidation, and
      extinction. KEY FINDINGS: Reconsolidation of PD mice occurred normally but memory
      extinction was facilitated in PD mice compared to control mice. Moreover, memory
      retention in PD mice was attenuated earlier than in controls following repeated
      conditioned stimuli every day. SIGNIFICANCE: PD mice with selective loss of
      DAergic neurons in the SNpc showed attenuated memory retention, probably via
      facilitated extinction learning.

PMID- 26209140
TI  - The potential of asiaticoside for TGF-beta1/Smad signaling inhibition in
      prevention and progression of hypoxia-induced pulmonary hypertension.
AB  - AIMS: Asiaticoside (AS) is a saponin monomer extracted from the medicinal plant
      Centella asiatica, which has a variety of biological effects. We intended to
      investigate the effects of asiaticoside on a hypoxia-induced pulmonary
      hypertension (HPH) rat model and examine the possible effects of asiaticoside on
      TGF-beta1/Smad signaling in vivo and in vitro. MAIN METHODS: The rat HPH model
      was established by hypoxic exposure and asiaticoside was administered for four
      weeks. Parameters including the mean pulmonary artery pressure (mPAP), the right
      ventricular hypertrophy (RVH) and the percentage of medial wall thickness were
      used to evaluate the development of HPH. TGF-beta1, TGF-beta receptor, Smad2/3
      and phospho-Smad2/3 expressions were detected and the proliferation, migration
      and apoptosis of pulmonary arterial smooth muscle cells (PASMCs) adjusted by
      asiaticoside under the hypoxic condition were evaluated. KEY FINDINGS: Our data
      indicate that asiaticoside attenuated pulmonary hypertension, pulmonary vascular
      remodeling and RV hypertrophy in HPH rats, which was probably mediated by
      restraining the hypoxia-induced overactive TGF-beta1/Smad2/3 signaling and
      inhibiting the proliferation by inducing apoptosis of the PASMCs. SIGNIFICANCE:
      Given the preventative potential in animal models and in vitro, we propose
      asiaticoside as a promising protective treatment in HPH.

PMID- 26209141
TI  - Quercetin intraperitoneal administration ameliorates lipopolysaccharide-induced
      systemic inflammation in mice.
AB  - AIMS: The purpose of this study was to unravel pharmacological effects of
      quercetin (Q) on systemic inflammation in septic mice, and compare it to
      quercetin-3-glucuronide (Q3G), a major metabolite of Q. MAIN METHODS: A suitable
      sepsis mouse model was first established using lipopolysaccharide (LPS) injected
      intraperitoneally (i.p.). Q or Q3G was administered i.p. to septic mice in a
      prophylactic or therapeutic manner. Pro-inflammatory (TNF-alpha, IL-1beta and IL
      6) and anti-inflammatory (IL-10) cytokine secretion profiles by peritoneal
      macrophages of the mice were measured using ELISA. KEY FINDINGS: Mice which
      received 8mg/kg BW LPS i.p. for 12h resulted in intermediate systemic
      inflammation, suggesting a useful mild septic mouse model. At non-toxic doses, Q
      or Q3G (0.06 or 0.15MUmol/mouse) i.p. injected in a prophylactic manner
      significantly (P<0.05) increased anti-inflammatory IL-10 secretions by peritoneal
      macrophages of the LPS-induced septic mice. Q, but not Q3G, i.p. injected in a
      therapeutic manner significantly (P<0.05) increased IL-10 secretions by
      peritoneal macrophages of the septic mice. SIGNIFICANCE: Our data suggest that Q,
      but not Q3G, has pharmacological effects to ameliorate systemic inflammation.
      These results are the first to show that Q has potent potential against sepsis in
      both prophylactic and therapeutic manners in vivo.

PMID- 26209142
TI  - The difference in learning culture and learning performance between a traditional
      clinical placement, a dedicated education unit and work-based learning.
AB  - BACKGROUND: An experiment was carried out on the bachelor's degree course in
      nursing with two new clinical placement concepts: workplace learning and the
      dedicated education centre. The aim was to establish a learning culture that
      creates a sufficiently high learning performance for students. OBJECTIVES: The
      objectives of this study are threefold: (1) to look for a difference in the
      "learning culture" and "learning performance" in traditional clinical placement
      departments and the new clinical placement concepts, the "dedicated education
      centre" and "workplace learning"; (2) to assess factors influencing the learning
      culture and learning performance; and (3) to investigate whether there is a link
      between the learning culture and the learning performance. METHOD: A non
      randomised control study was carried out. The experimental group consisted of 33
      final-year nursing undergraduates who were following clinical placements at
      dedicated education centres and 70 nursing undergraduates who undertook workplace
      learning. The control group consisted of 106 students who followed a traditional
      clinical placement. The "learning culture" outcome was measured using the
      Clinical Learning Environment, Supervision and Nurse Teacher scale. The "learning
      performance" outcome consisting of three competencies was measured using the
      Nursing Competence Questionnaire. RESULTS: The traditional clinical placement
      concept achieved the highest score for learning culture (p<0.001). The new
      concepts scored higher for learning performance of which the dedicated education
      centres achieved the highest scores. The 3 clinical placement concepts showed
      marked differences in learning performance for the "assessment" competency
      (p<0.05) and for the "interventions" competency (p<0.05). CONCLUSIONS:
      Traditional clinical placement, a dedicated education centre and workplace
      learning can be seen as complementary clinical placement concepts. The
      organisation of clinical placements under the dedicated education centre concept
      and workplace learning is recommended for final-year undergraduate nursing
      students.

PMID- 26209143
TI  - The Basics of the Sunshine Act: How It Pertains to the Practicing Orthopaedic
      Surgeon.
AB  - The Physician Payments Sunshine Act is a disclosure law requiring all drug,
      medical device, and biologics companies to report transfers of value to
      physicians and teaching hospitals. It was passed into law in 2010 as part of the
      Affordable Care Act. The first set of data was released via an online public
      database on September 30, 2014, with subsequent annual reports to come. Three
      categories of payments are recorded: general payments, ownership interests, and
      research payments. With few exceptions, any transfer of value greater than $10 is
      reported. The first dataset of 4.4 million payments totaling more than $3.5
      billion was released amidst controversy and technical problems. Identified data
      constituted $1.3 billion in transfer payments; de-identified data constituted
      $2.2 billion in payments. Data regarding an additional $1.1 billion in payments
      were not published, in part because of unresolved disputes. The largest amount of
      funding went to research payments. The highest proportion of general payments
      went to licensing and royalty payments. Orthopaedic surgeons comprised 3.5% of
      the physicians represented, and they were responsible for more than 20% of total
      payments. The full impact of the Sunshine Act will not be clear until several
      years after its implementation. 

PMID- 26209144
TI  - Ray Resections of the Fingers: Indications, Techniques, and Outcomes.
AB  - Ray resection, which was pioneered by Bunnell in the 1920s, was initially
      performed as a salvage procedure for dysfunction of the proximal interphalangeal
      joint. Successful ray resection with or without an adjacent ray transfer can be
      useful for treating vascular insufficiency, tumors, infection, trauma, recurrent
      Dupuytren contracture, and congenital abnormalities of the hand. Indications,
      techniques, and outcomes vary based on the digit and the number of digits
      resected. Compared with amputation at the proximal phalangeal level, a single ray
      resection has better cosmesis and similar function, resulting in improved patient
      satisfaction. However, a 15% to 30% loss in grip and pinch strength has been
      reported. Today, ray resection results in good cosmetic and functional outcomes
      when preservation of a functional digit is unattainable or when the presence of
      an abnormal, unreconstructable digit interferes with the overall hand function. 

PMID- 26209145
TI  - Psychological Aspects of Recovery Following Anterior Cruciate Ligament
      Reconstruction.
AB  - Recovery following anterior cruciate ligament reconstruction is an arduous
      process that requires a significant mental and physical commitment to
      rehabilitation. Orthopaedic research in recent years has focused on optimizing
      anterior cruciate ligament surgical techniques; however, despite stable anterior
      cruciate ligament reconstructions, many athletes still never achieve their
      preinjury ability or even return to sport. Psychological factors associated with
      patient perceptions and functional outcomes following anterior cruciate ligament
      reconstruction are important to acknowledge and understand. Issues related to
      emotional disturbance, motivation, self-esteem, locus of control, and self
      efficacy can have profound effects on patients' compliance, athletic identity,
      and readiness to return to sport. The psychological aspects of recovery play a
      critical role in functional outcomes, and a better understanding of these
      concepts is essential to optimize the treatment of patients undergoing anterior
      cruciate ligament reconstruction, particularly those who plan to return to sport.
      Identifying at-risk patients, encouraging a multidisciplinary approach to patient
      care, and providing early referral to a sports psychologist may improve patient
      outcomes and increase return-to-play rates among athletes. 

PMID- 26209146
TI  - Technical Considerations in the Treatment of Syndesmotic Injuries Associated With
      Ankle Fractures.
AB  - Malleolar ankle fractures associated with syndesmotic injuries are common.
      Diagnosis of the syndesmotic injury can be difficult and often requires
      intraoperative fluoroscopic stress testing. Accurate reduction and stable
      fixation of the syndesmosis are critical to maximize patient outcomes. Recent
      literature has demonstrated that the unstable syndesmosis is particularly prone
      to iatrogenic malreduction. Multiple types of malreduction can occur, including
      translational, rotational, and overcompression. Knowledge of the technical
      details regarding intraoperative reduction methods and reduction assessment can
      minimize the risk of syndesmotic malreduction and improve patient outcomes. 

PMID- 26209147
TI  - The AAOS Resident Assembly.

PMID- 26209148
TI  - Principles of Antibiotic Prophylaxis in Total Joint Arthroplasty: Current
      Concepts.
AB  - Infection is a rare, serious complication following total joint arthroplasty and
      constitutes a considerable emotional and financial burden for patients, surgeons,
      and healthcare systems. Prevention of surgical site and periprosthetic joint
      infections is crucial. This requires knowledge of the microorganisms that
      commonly cause these infections, including Staphylococcus species. Selection of
      the appropriate antibiotic regimen to treat infection remains controversial, but
      cefazolin and cefuroxime are the most commonly recommended antibiotics for
      prophylaxis. Appropriate timing of administration before surgery, with redosing
      performed as needed, can help to ensure optimal antibiotic concentration during
      surgery. Given the increasing evidence that S aureus colonization is a risk
      factor for periprosthetic joint infection, an exploration of the potential
      benefits of preoperative S aureus carrier screening and decolonization protocols
      is warranted. The use of antibiotic-loaded bone cement in primary total joint
      arthroplasty and antibiotic powder at wound closure are other controversial
      topics that require additional research. 

PMID- 26209149
TI  - External Beam Radiation Therapy for Orthopaedic Pathology.

PMID- 26209150
TI  - Slow Microbial Life in the Seabed.
AB  - Global microbial cell numbers in the seabed exceed those in the overlying water
      column, yet these organisms receive less than 1% of the energy fixed as organic
      matter in the ocean. The microorganisms of this marine deep biosphere subsist as
      stable and diverse communities with extremely low energy availability. Growth is
      exceedingly slow, possibly regulated by virus-induced mortality, and the mean
      generation times are tens to thousands of years. Intermediate substrates such as
      acetate are maintained at low micromolar concentrations, yet their turnover time
      may be several hundred years. Owing to slow growth, a cell community may go
      through only 10,000 generations from the time it is buried beneath the mixed
      surface layer until it reaches a depth of tens of meters several million years
      later. We discuss the efficiency of the energy-conserving machinery of subsurface
      microorganisms and how they may minimize energy consumption through necessary
      maintenance, repair, and growth. 

PMID- 26209151
TI  - A comparative adsorption study: 17beta-estradiol onto aerobic granular sludge and
      activated sludge.
AB  - Adsorption plays a significant role in removing hydrophobic 17beta-estradiol (E2)
      from wastewater. Batch experiments were conducted to compare the adsorption of E2
      onto activated aerobic granular sludge (AGS) and activated sludge (AS), and
      features evaluated included the adsorption kinetics, thermodynamics, and
      influence of other environmental factors. By using a non-chemical wet-heat
      technique, both AGS and AS were treated to inactivated status. Then, after
      loading E2, the adsorption equilibrium capacity of the AGS was found to be
      greater than that of the AS at the same initial concentration of E2. Moreover,
      both the adsorption processes corresponded to a pseudo-second-order kinetic
      model; the adsorption rate constant of AGS was found to be higher and the half
      adsorption time was shorter than that of AS. Next, evaluations of adsorption
      isotherms and thermodynamics indicated that the adsorption process was mainly a
      physical process. Lower temperatures facilitated a higher equilibrium adsorption
      capacity. However, the adsorption binding sites of AGS were distributed more
      uniformly at higher temperature, in contrast to the distribution found for AS.
      Finally, acidic conditions and an appropriate ionic strength (0.4 mol/L) were
      found to be particularly conducive to the adsorption process. Overall, the
      results showed that AGS has the potential to adsorb E2 with significant
      efficiency, thereby offering a new and more efficient means of treating E2 and
      trace oestrogens in wastewater. 

PMID- 26209152
TI  - Rapidly activated epidermal growth factor receptor mediates lipopolysaccharide
      triggered migration of microglia.
AB  - Previous reports have suggested that epidermal growth factor receptor (EGFR) is
      involved in microglia activation characterized by cell morphology changes,
      cytokine production and cell migration; and the biochemical regulation of the
      microglia migration is a potential therapeutic target following CNS inflammatory
      damages. However, the role of EGFR in microglia motility after inflammatory
      stimulation remains unknown. In the present study, lipopolysaccharide (LPS) was
      found to trigger rapid EGFR phosphorylation within 10 min, which was sustained
      during long-term stimulation in both primary microglial cells and the cultured
      BV2 microglial cells, furthermore, blocking EGFR phosphorylation by AG1478
      significantly attenuated the LPS-induced chemotactic and chemokinetic migration
      of microglia. In addition, LPS could initiate calcium oscillation in microglia
      during live-cell recording, however, an intracellular calcium chelator and a
      selective inhibitor of calcium/calmodulin-dependent protein kinase II, but not an
      extracellular calcium chelator, remarkably suppressed the LPS-induced EGFR
      phosphorylation in BV2 microglia cells. As EGFR is not a traditional receptor for
      LPS, these findings suggest that the rapid phosphorylation of EGFR is attributed
      to the LPS-triggered intracellular calcium mobilization. By examining the
      downstream signals of EGFR, we further proved that extracellular signal-regulated
      kinase (ERK) is essential for EGFR-mediated microglia migration, because ERK
      inhibition attenuated the chemotactic and chemokinetic migration of microglia
      that had been induced by either LPS or EGF. Collectively, these results suggest
      that LPS could trigger the rapid phosphorylation of EGFR and subsequent ERK
      activation through mobilizing calcium activity, which underlies the microglia
      migration in an inflammatory condition. 

PMID- 26209153
TI  - Crocin protects PC12 cells against MPP(+)-induced injury through inhibition of
      mitochondrial dysfunction and ER stress.
AB  - The molecular machinery that mediates neuronal injury in neurodegenerative
      conditions such as Parkinson's disease (PD) remains to be fully deciphered, which
      will hopefully provide novel therapeutic targets for these disorders. Crocin, one
      of the water-soluble carotenoids isolated from the Crocus sativus L (saffron)
      stigma, has been reported to exert therapeutic potential in many disease models.
      Here, we establish an in vitro PD model using 1-methyl-4-phenylpyridinium
      (MPP(+))-injured PC12 cells to investigate the protective effects of crocin.
      Crocin treatment significantly attenuated MPP(+)-induced cell injury and
      apoptosis with little toxicity, and these protective effects were still observed
      even if crocin treatment was delayed to 6 h after injury. Crocin also inhibited
      MPP(+)-induced mitochondrial dysfunction, as evidenced by preservation of
      mitochondrial membrane potential (MMP) and ATP synthesis, which correlates with
      suppressed endoplasmic reticulum (ER) stress through inhibiting ER chaperone and
      ER related apoptotic factors. In addition, ER calcium release and morphological
      changes in ER lumen after MPP(+) exposure were all partially prevented by crocin.
      By using specific targeted small interfering RNA (siRNA) to knockdown the
      expression of the C/EBP homologous protein (CHOP), we found that crocin-induced
      protection and inhibition of ER stress was mediated by inverting MPP(+)-induced
      decrease of Wnt through the CHOP pathway. Our study demonstrates a pivotal role
      of ER stress in mediating PD related neuronal injury via the regulation of CHOP
      Wnt pathway, and suggests the therapeutic values of crocin against ER stress
      associated cytotoxicity. 

PMID- 26209154
TI  - Caffeine prevents d-galactose-induced cognitive deficits, oxidative stress,
      neuroinflammation and neurodegeneration in the adult rat brain.
AB  - d-galactose has been considered a senescent model for age-related
      neurodegenerative disease. It induces oxidative stress which triggers memory
      impairment, neuroinflammation and neurodegeneration. Caffeine act as anti-oxidant
      and has been used in various model of neurodegenerative disease. Nevertheless,
      the effect of caffeine against d-galactose aging murine model of age-related
      neurodegenerative disease elucidated. Here, we investigated the neuroprotective
      effect of caffeine against d-galactose. We observed that chronic treatment of
      caffeine (3 mg/kg/day intraperitoneally (i.p) for 60 days) improved memory
      impairment and synaptic markers (Synaptophysin and PSD95) in the d-galactose
      treated rats. Chronic caffeine treatment reduced the oxidative stress via the
      reduction of 8-oxoguanine through immunofluorescence in the d-galactose-treated
      rats. Consequently caffeine treatment suppressed stress kinases p-JNK.
      Additionally, caffeine treatment significantly reduced the d-galactose-induced
      neuroinflammation through alleviation of COX-2, NOS-2, TNFalpha and IL-1beta.
      Furthermore we also analyzed that caffeine reduced cytochrome C, Bax/Bcl2 ratio,
      caspase-9, caspase-3 and PARP-1 level. Moreover by evaluating the
      immunohistochemical results of Nissl and Fluro-Jade B staining showed that
      caffeine prevented the neurodegeneration in the d-galactose-treated rats. Our
      results showed that caffeine prevents the d-galactose-induced oxidative stress
      and consequently alleviated neuroinflammation and neurodegeneration; and synaptic
      dysfunction and memory impairment. Therefore, we could suggest that caffeine
      might be a dietary anti-oxidant agent and a good candidate for the age-related
      neurodegenerative disorders. 

PMID- 26209155
TI  - Advanced Parameters of Cardiac Mechanics in Children with CKD: The 4C Study.
AB  - BACKGROUND AND OBJECTIVES: Newer parameters of cardiac mechanics provide
      additional insights on cardiac dysfunction in adult patients with CKD. The aim of
      this study was to identify prevalence of subclinical abnormalities in cardiac
      function through the analysis of novel indices of cardiac mechanics in a large
      population of children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Between 2009 and 2011, the prospective observational Cardiovascular Comorbidity
      in Children with CKD Study enrolled patients with CKD ages 6-17 years old with
      eGFR=10-45 ml/min per 1.73 m(2) in 14 European countries. Cardiac morphology and
      function were assessed through echocardiography. The analysis presented
      encompasses global radial, longitudinal, and circumferential strains as well as
      time to peak analysis. Data were compared with 61 healthy children with
      comparable age and sex. RESULTS: Data on 272 patients with CKD with complete
      echocardiographic assessment are reported (age =12.8+/-3.5 years old; 65% boys).
      Patients with CKD showed mildly higher office BP values and higher prevalence of
      left ventricular hypertrophy, but no differences were observed among groups in
      left ventricular ejection fraction. Strain analysis showed significantly lower
      global radial strain (29.6%+/-13.3% versus 35.5%+/-8.9%) and circumferential
      strain components (-21.8%+/-4.8% versus -28.2%+/-5.0%; both P<0.05) in patients
      with CKD without significant differences observed in longitudinal strain (
      15.9%+/-3.4% versus -16.2%+/-3.7%). Lower values of global radial strain were
      associated with lower circumferential endocardial-to-epicardial gradient (r=0.51;
      P<0.01). This association remained significant after adjusting for BP, eGFR, and
      presence of left ventricular hypertrophy. Eventually, patients with CKD also
      showed higher delay in time to peak cardiac contraction (58+/-28 versus 37+/-18
      milliseconds; P<0.05). CONCLUSIONS: A significant proportion of children with CKD
      show impaired systolic mechanics. Impaired systolic function is characterized by
      lower radial strain, transmural circumferential gradient, and mild cardiac
      dyssynchrony. This study suggests that analysis of cardiac strain is feasible in
      a large multicenter study in children with CKD and provides additional
      information on cardiac pathophysiology of this high-risk population.

PMID- 26209156
TI  - The Golden Hours of AKI: Is Oxygen Delivery the Key?

PMID- 26209157
TI  - Low Systemic Oxygen Delivery and BP and Risk of Progression of Early AKI.
AB  - BACKGROUND AND OBJECTIVES: The optimal hemodynamic management of patients with
      early AKI is unknown. This study aimed to investigate the association between
      hemodynamic parameters in early AKI and progression to severe AKI and hospital
      mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study
      retrospectively analyzed the data of all patients admitted to the adult intensive
      care unit in a tertiary care center between July 2007 and June 2009 and
      identified those with stage 1 AKI (AKI I) per the AKI Network classification. In
      patients in whom hemodynamic monitoring was performed within 12 hours of AKI I,
      hemodynamic parameters in the first 12 hours of AKI I and on the day of AKI III
      (if AKI III developed) or 72 hours after AKI I (if AKI III did not develop) were
      recorded. Risk factors for AKI III and mortality were identified using univariate
      and multivariate logistic regression analyses. RESULTS: Among 790 patients with
      AKI I, 210 (median age 70 years; 138 men) had hemodynamic monitoring within 12
      hours of AKI I; 85 patients (41.5%) progressed to AKI III and 91 (43%) died in
      the hospital. AKI progressors had a significantly higher Sequential Organ Failure
      Assessment score (8.0 versus 9.6; P<0.001), lower indexed systemic oxygen
      delivery (DO2I) (median 325 versus 405 ml/min per m(2); P<0.001), higher central
      venous pressure (16 versus 13; P=0.02), and lower mean arterial blood pressure
      (MAP) (median 71 versus 74 mmHg; P=0.01) in the first 12 hours of AKI I compared
      with nonprogressors. Multivariate analysis confirmed that raised lactate, central
      venous pressure, and Sequential Organ Failure Assessment score as well as
      mechanical ventilation were independently associated with progression to AKI III;
      higher DO2I and MAP were independently associated with a lower risk of AKI III
      but not survival. The associations were independent of sepsis, heart disease,
      recent cardiac surgery, or chronic hypertension. CONCLUSIONS: Higher DO2I and MAP
      in early AKI were independently associated with a lower risk of progression.

PMID- 26209158
TI  - Risk of Stroke in Patients with ESRD.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to determine absolute and excess
      stroke risks in people with ESRD compared with the general population. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This cohort study used data linkage
      between the Australia and New Zealand Dialysis and Transplant Registry and
      hospital and death records for 10,745 people with ESRD in New South Wales from
      2000 to 2010. For the general population, Australian Institute of Health and
      Welfare hospital usage records and Australian Bureau of Statistics census data
      were used. Rates and standardized incidence rate ratios of hospitalization with a
      stroke were calculated. RESULTS: People with ESRD had 640 hospitalizations with
      stroke in 49,472 person-years of follow-up (1294 per 100,000 person-years), and
      people in the general population had 338,392 hospitalizations with stroke (212
      per 100,000 person-years), an incidence rate ratio of 3.32 (95% confidence
      interval, 3.31 to 3.33). Excess risk was greater for women (incidence rate ratio,
      5.14; 95% confidence interval, 5.11 to 5.18) than men (incidence rate ratio,
      2.52; 95% confidence interval, 2.51 to 2.54; P for interaction <0.001) and
      decreased with age. People ages 35-39 years old with ESRD had an 11 times
      increased risk of stroke (incidence rate ratio, 11.08; 95% confidence interval,
      9.41 to 13.05), and risk in people ages >=85 years old increased 2-fold
      (incidence rate ratio, 2.04; 95% confidence interval, 1.87 to 2.23; P for
      interaction <0.001). Excess risk was greater for intracerebral hemorrhage
      (incidence rate ratio, 4.18; 95% confidence interval, 4.11 to 4.26) than ischemic
      stroke (incidence rate ratio, 3.43; 95% confidence interval, 3.40 to 3.45; P for
      interaction <0.01). CONCLUSIONS: People with ESRD have a substantially higher
      risk of stroke, particularly women and young people, and hemorrhagic stroke.
      Future work could investigate effective and safe interventions for primary and
      secondary prevention of stroke in people with ESRD.

PMID- 26209159
TI  - A Novel Naphthalene-Immobilized Nanoporous SBA-15 as a Highly Selective Optical
      Sensor for Detection of Fe(3+) in Water.
AB  - A novel organic-inorganic hybrid optical sensor (SBA-NCO) was designed and
      synthesized through immobilization of isocyanatopropyl-triethoxysilane and 1
      amino-naphthalene onto the surface of SBA-15 by post-grafting method. The
      characterization of materials using XRD, TEM, N2 adsorption-desorption, and FT-IR
      techniques confirmed the successful attachment of organic moieties and preserving
      original structure of SBA-15 after modification step. Fluorescence experiments
      demonstrated that SBA-NCO was a highly selective optical sensor for the detection
      of Fe(3+) directly in water over a wide range of metal cations including Na(+),
      Mg(2+), Al(3+), K(+), Ca(2+), Cr(3+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+),
      Zn(2+), Cd(2+), Hg(2+), and Pb(2+) in a wide pH values. 

PMID- 26209160
TI  - The effects of lanthanum chloride on proliferation and apoptosis of cervical
      cancer cells: involvement of let-7a and miR-34a microRNAs.
AB  - Lanthanide elements have been documented to possess various biologic effects, and
      their compounds have been studied intensely for their anti-cancer potential.
      However, the underlying mechanisms remain largely unknown. In the present study,
      we propose that the levels of proliferation and apoptosis related microRNAs
      (miRNAs), let-7a and miR-34a, which mediate the apoptosis of cervical cancer
      cells, can be affected by the lanthanum ion. Our data showed that LaCl3 inhibited
      the proliferation and induced the apoptosis of cervical cancer cells both in vivo
      and in vitro by regulating let-7a, miR-34a and their downstream genes. This study
      provides novel evidence demonstrating that the anticancer mechanism of lanthanum
      chloride is partially attributed to miRNAs regulation and establishes an
      experimental basis for the clinical application of lanthanum chloride as an anti
      cancer drug. 

PMID- 26209161
TI  - Effect of wrist and interphalangeal thumb movement on zone T2 flexor pollicis
      longus tendon tension in a human cadaver model.
AB  - INTRODUCTION: Therapy after flexor pollicis longus (FPL) repair typically mimics
      finger flexor management, but this ignores anatomic and biomechanical features
      unique to the FPL. PURPOSE OF THE STUDY: We measured FPL tendon tension in zone
      T2 to identify biomechanically appropriate exercises for mobilizing the FPL.
      METHODS: Eight human cadaver hands were studied to identify motions that
      generated enough force to achieve FPL movement without exceeding hypothetical
      suture strength. RESULTS: With the carpometacarpal and metacarpophalangeal joints
      blocked, appropriate forces were produced for both passive interphalangeal (IP)
      motion with 30 degrees  wrist extension and simulated active IP flexion from 0
      degrees  to 35 degrees  with the wrist in the neutral position. DISCUSSION: This
      work provides a biomechanical basis for safely and effectively mobilizing the
      zone T2 FPL tendon. CONCLUSION: Our cadaver study suggests that it is safe and
      effective to perform early passive and active exercise to an isolated IP joint.
      LEVEL OF EVIDENCE: NA.

PMID- 26209162
TI  - Responsiveness of three Patient Report Outcome (PRO) measures in patients with
      hand fractures: A preliminary cohort study.
AB  - STUDY DESIGN: Clinical measurement. INTRODUCTION: Few studies describe the
      responsiveness of functional outcomes measures in patients sustaining hand
      fractures. PURPOSE: 1--To explore the responsiveness of three function-oriented
      Patient Report Outcome (PRO) measures with a cohort of hand fracture patients. 2-
      To examine patients' PRO preference. METHODS: 60 participants with 74 hand
      fractures at an outpatient hospital-based hand therapy clinic consented to
      participate in this study. They completed the Disabilities of the Arm, Shoulder,
      and Hand Questionnaire (DASH), Michigan Hand Outcomes Questionnaire (MHQ), and
      Patient-Rated Wrist/Hand Evaluation (PRWHE) at three trials: T1 (evaluation), T2
      (one month later), and T3 (two months later). Participants also identified which
      PRO they felt best reflected their hand use and which was easiest to complete.
      Descriptive statistics, analyses of variance (ANOVA), effect size, and
      standardized response mean (SRM) were employed to describe participants,
      determine functional change between trials, and examine and compare PRO
      responsiveness. Questionnaire preference at T1 was reported. RESULTS:
      Participants demonstrated functional improvement, as measured by the DASH, PRWHE,
      and MHQ. T1 scores: DASH = 41.85 (SD +/- 22.78), MHQ = 50.13 (SD +/- 18.36), and
      PRWHE = 48.18 (SD +/- 22.07). T2 scores: DASH = 22.11 (SD +/- 18.18), MHQ = 69.89
      (SD +/- 15.93), and PRWHE = 22.62 (SD +/- 18.15). T3 scores: DASH = 17.56 (SD +/-
      18.01), MHQ = 75.37 (SD +/- 19.19), and PRWHE = 22.40 (SD +/- 19.04). Each PRO
      demonstrated significant test score differences between trials (p < .001). Large
      responsiveness (>=.80) was noted between T1 and T2: (effect size: .98-1.23; SRM:
      1.31-1.49) and T1 and T3 (effect size: 1.21-1.54; SRM 1.49-1.84). Smaller
      responsiveness effects were noted between T2 and T3 (effect size: .35-.64, SRM:
      .38-.81). No significant differences between questionnaire responsiveness were
      found. Patients reported PRWHE easiest to complete and MHQ best reflecting their
      hand use. CONCLUSIONS: DASH, MHQ, and PRWHE were each able to describe functional
      limitations in this cohort of patients with hand fractures. In capturing
      improvement over time they demonstrated comparable responsiveness in assessing
      change in patients with hand fractures. LEVEL OF EVIDENCE: 2c.

PMID- 26209163
TI  - Multiplanar wrist joint proprioception: The effect of anesthetic blockade of the
      posterior interosseous nerve or skin envelope surrounding the joint.
AB  - STUDY DESIGN: Randomized clinical trial. PURPOSE: Contribution of the posterior
      interosseous nerve (PIN) and surrounding skin envelope to wrist proprioception is
      a topic of debate and the primary focus of this research. METHODS: We performed a
      double-blinded, placebo control study in which subjects underwent baseline
      multiplanar testing of wrist proprioception. They were randomized to receive
      either anesthetic blockade of the PIN within the fourth dorsal compartment, or
      circumferential topical anesthetic blockade of skin surrounding the wrist.
      Corresponding opposite wrists underwent placebo intervention with saline
      injection or inert ultrasound gel. Subjects repeated proprioceptive testing.
      RESULTS: Eighty subjects, 45 male and 35 female, mean age 33 years (range, 19-64
      years), completed testing. The percentage of measurements falling outside a +/-18
      degrees  range did not differ between pre-treatment and post-treatment PIN
      blockade or for circumferential skin anesthesia. CONCLUSIONS: Wrist
      proprioception appears to be a multifactorial phenomenon. Surgeons may sacrifice
      the PIN without concern for effect on joint proprioception. LEVEL OF EVIDENCE:
      Level I.

PMID- 26209164
TI  - Stenosing flexor tenosynovitis: Validity of standard assessment tools of daily
      functioning and quality of life.
AB  - STUDY DESIGN: Cross-sectional. INTRODUCTION: Stenosing flexor tenosynovitis (SFT)
      is a common hand disease, yet there is a lack of valid standard assessments for
      this population. PURPOSE OF THE STUDY: Validation of assessment for the
      evaluation of disability and quality of life related to SFT clinical severity.
      METHODS: Sixty five participants with SFT were matched to 71 controls.
      Participant's symptoms were graded using the Quinnell classification. Disability
      and quality of life were evaluated using the DASH and WHOQOL-BREF questionnaires.
      RESULTS: Small to moderate correlations were found between SFT grade and the DASH
      and WHOQOL-BREF. Both questionnaires differentiated between the first and third
      clinical grades and between SFT and healthy groups. DISCUSSION: Both
      questionnaires are useful tools to distinguish between participants with SFT and
      controls and between mild and severe clinical grades. CONCLUSION: The DASH and
      WHOQOL-BREF may be implemented in the clinical management and research of SFT.
      LEVEL OF EVIDENCE: Diagnostic III.

PMID- 26209165
TI  - First dorsal interosseous muscle contraction results in radiographic reduction of
      healthy thumb carpometacarpal joint.
AB  - INTRODUCTION: Hand therapists selectively strengthen the first dorsal interosseus
      (FDI) to stabilize arthritic joints yet the role of the FDI has not yet been
      radiographically validated. PURPOSE: To determine if FDI contraction reduces
      radial subluxation (RS) of the thumb metacarpal (MC). METHODS: Fluoroscopy was
      used to obtain true anterior-posterior radiographs of non-arthritic CMC joints:
      1) at rest, 2) while stressed and 3) while stressed with maximal FDI contraction.
      Maximal FDI strength during CMC stress and thumb MC RS and trapezial articular
      width were measured. The ratio of RS to the articular width was calculated.
      RESULTS: Seventeen participants (5 male, 12 female) participated. Subluxation of
      a stressed CMC significantly reduced and the subluxation to articular width ratio
      significantly improved after FDI activation. CONCLUSIONS: Contraction of the FDI
      appears to radiographically reduce subluxation of the healthy thumb CMC joint.
      Further exploration on the FDI's reducibility and its carry-over effects in
      arthritic thumbs is needed. LEVEL OF EVIDENCE: 4.

PMID- 26209166
TI  - Eldecalcitol improves muscle strength and dynamic balance in postmenopausal women
      with osteoporosis: an open-label randomized controlled study.
AB  - The antifracture efficacy of vitamin D in osteoporosis is due to its direct
      action on bones and indirect extraskeletal effects to prevent falls. Eldecalcitol
      is an analog of active vitamin D3 that improves bone mineral density and reduces
      the risk of osteoporotic fractures. However, the effects of eldecalcitol on
      muscle strength and static and dynamic postural balance are unclear. In this open
      label randomized controlled study, we assessed the effects of eldecalcitol on
      muscle strength and static and dynamic postural balance in 50 postmenopausal
      women (mean age 74 years) with osteoporosis treated with bisphosphonate.
      Participants were randomly divided into a bisphosphonate group (alendronate at 35
      mg/week; n = 25) or an eldecalcitol group (eldecalcitol at 0.75 MUg/day and
      alendronate at 35 mg/week; n = 25) and were followed up for 6 months. Trunk
      muscle strength, including back extensor strength and iliopsoas muscle strength,
      was measured. Static standing balance was evaluated and the one leg standing test
      was performed to assess static postural balance. Dynamic sitting balance was
      evaluated and the 10-m walk test, functional reach test, and timed up and go test
      were performed to assess dynamic postural balance. At 6 months, there were no
      significant changes in any measure of muscle strength or balance in the
      bisphosphonate group, whereas eldecalcitol significantly increased back extensor
      strength (p = 0.012) and iliopsoas muscle strength (p = 0.035). Eldecalcitol also
      significantly improved findings on the timed up and go test (p = 0.001) and
      dynamic sitting balance (p = 0.015) at 6 months. These results with eldecalcitol
      may have an impact on prevention of falls. 

PMID- 26209167
TI  - Esomeprazole use is independently associated with significant reduction of BMD: 1
      year prospective comparative safety study of four proton pump inhibitors.
AB  - Because of the efficacy of proton pump inhibitors (PPIs), their the use is
      increasing dramatically. The risk of adverse effects of short-term PPI therapy is
      low, but there are important safety concerns for potential adverse effects of
      prolonged PPI therapy. Findings from studies assessing the association between
      PPI use and bone mineral density (BMD) and/or fracture risk are contradictory.
      The aim of this study was to prospectively assess potential association of PPI
      treatment with the 12-month change in BMD of the lumbar spine, femur neck, and
      total hip. The study was performed in 200 PPI users and 50 PPI nonusers. Lumbar
      spine (L1-L4), femur neck, and total hip BMD were measured by dual-energy X-ray
      absorptiometry at the baseline and at 12 months. A total of 209 subjects
      completed the entire 12 months of the study and were included in the final
      analysis. A Wilcoxon signed-rank test showed that at 12 months PPI use was
      associated with statistically significant reductions in femur neck and total hip
      T scores (Z = -2.764, p = 0.005 and Z = -3.281, p = 0.001, respectively). A
      multiple linear regression analysis showed that only esomeprazole added
      significantly to the prediction of total lumbar spine and femur neck T scores (p
      = 0.048 and p = 0.037, respectively). Compared with the baseline, 12 months of
      PPI treatment resulted in lower femur neck and total hip BMD T scores. Among the
      four PPIs studied, esomeprazole was independently associated with significant
      reduction of BMD, whereas omeprazole had no effects on BMD. Considering the
      widespread use of PPIs, BMD screening should be considered in the case of
      prolonged PPI use. 

PMID- 26209168
TI  - Particulate accumulations in the vital organs of wild Brevoortia patronus from
      the northern Gulf of Mexico after the Deepwater Horizon oil spill.
AB  - Histopathologic lesions were observed in the commercially important filter
      feeding fish, Brevoortia patronus (Gulf menhaden), along the Louisiana Gulf
      Coast. Menhaden collected from Louisiana waters in 2011 and 2012, 1 and 2 years
      following the Deepwater Horizon oil spill, showed varying severities of gill
      lesions as well as an unusual accumulation of black particulates visible at
      necropsy in the heart and stomach vasculature. The PAH derived particulates were
      typically 1-4 um in diameter, but larger aggregates were observed in the coronary
      vessels on the ventricle surfaces and their location and size was confirmed by
      light microscopy. Composited particulate composition was consistent with
      weathered petrogenic polycyclic aromatic hydrocarbon (PAH) mixtures based on GC
      MS analysis. Particulates were present in 63 and 80% of fish hearts and 70 and
      89% of stomach muscularis collected in 2011 and 2012, respectively. Tissue
      embedded particulates can lead to localized cellular damage from bioavailable
      compounds, as well as chronic effects from occlusion of sensitive tissues' blood
      flow. The PAH derived particulates appeared to act as emboli in small
      capillaries, and could associated with localized inflammation, focal necrosis and
      inappropriate collagen and fibroblast tissue repair. We believe large volume
      filter feeding teleosts, such as menhaden (up to 3 million gallons per year/fish)
      with high lipid content, have a higher exposure risk and greater potential for
      toxicity from toxic particulates than other higher trophic level finfish.
      Suspended PAH derived particulates following an oil spill therefore, should be
      considered when assessing long-term ecological impacts and not be limited to
      physical contact (coating) or water soluble fractions for assessing toxicity
      (gill and neurologic).

PMID- 26209169
TI  - Biochemical and growth performance of the aquatic macrophyte Azolla filiculoides
      to sub-chronic exposure to cylindrospermopsin.
AB  - Physiological and biochemical effects of cylindrospermopsin (CYN), a
      cyanobacterial toxin that inhibits protein synthesis and released during a
      harmful cyanobacterial bloom, has been overlooked in plants. Therefore, at the
      present research, the toxic effects (physiological and biochemical) of a crude
      extract containing CYN were assessed in the aquatic fern Azolla filiculoides
      exposed to three concentrations (0.05, 0.5 and 5 MUg CYN mL(-1)). At 5 MUg CYN
      mL(-1), fern growth rate has showed a drastic decrease (0.001 g g(-1) day(-1))
      corresponding to a 99.8% inhibition, but at the concentrations of 0.05 and 0.5
      MUg CYN mL(-1) the growth rate was similar to the control plants. Growth rate
      also indicated a IC50 of 2.9 MUg CYN mL(-1). Those data point to the presence of
      other compounds in the crude extract may stimulate the fern growth and/or the
      fern is tolerant to CYN. Chlorophyll (a and b), carotenoids and protein content
      as well as the activities of glutathione reductase (GR) and glutathione-S
      transferase (GST) has increased at 5 MUg CYN mL(-1) which may indicate that
      photosynthesis and protein synthesis are not affected by CYN and the probable
      activation of defense and detoxifying mechanisms to overcome the effects induced
      by the presence of CYN. Low uptake of cylindrospermopsin (1.314 MUg CYN g(-1) FW)
      and low bioconcentration factor (0.401) point towards to a safe use of A.
      filiculoides as biofertilizer and as food source, but also indicate that the fern
      is not suitable for CYN phytoremediation.

PMID- 26209171
TI  - Effectiveness of medical interventions.
AB  - To be effective, a medical intervention must improve one's health by targeting a
      disease. The concept of disease, though, is controversial. Among the leading
      accounts of disease-naturalism, normativism, hybridism, and eliminativism-I
      defend a version of hybridism. A hybrid account of disease holds that for a state
      to be a disease that state must both (i) have a constitutive causal basis and
      (ii) cause harm. The dual requirement of hybridism entails that a medical
      intervention, to be deemed effective, must target either the constitutive causal
      basis of a disease or the harms caused by the disease (or ideally both). This
      provides a theoretical underpinning to the two principle aims of medical
      treatment: care and cure. 

PMID- 26209170
TI  - Psychological Interventions for the Management of Chronic Pain: a Review of
      Current Evidence.
AB  - Chronic pain is a complex disorder to which medical and psychological factors
      both contribute and react. While there are numerous chronic pain conditions, they
      share certain experiences. This review examines some of the psychological factors
      that are common to the pain experience and some of the psychologically-based
      treatments that have been utilized in conduction with medical treatments for
      pain. In light of the fact that there is not yet a "gold standard" in this
      regard, it ends with the challenge to develop coherent and effective multi-model
      treatments that draw upon the successes that have been demonstrated so far. 

PMID- 26209172
TI  - Transition From Child to Adult Care--'It's Not a One-Off Event': Development of
      Benchmarks to Improve the Experience.
AB  - The transition from child to adult services is a crucial time in the health of
      young people who may potentially fall into a poorly managed 'care gap'. A multi
      site, multi-staged study was undertaken to identify the key aspects of a
      transitional programme of care for young people. Through a process of mapping,
      which involved drawing on primary and secondary data, a clinical practice
      benchmark tool was developed. Benchmarks are a health care quality performance
      measurement 'tool'. They provide clinical teams with standards that services can
      measure themselves against to see how they are doing. They are used in a
      comparing and sharing activity, using a structured and systematic approach, to
      share best practice. They offer a mechanism to look at processes, and provide an
      opportunity to analyse skills and attitudes, which may be the hidden narrative in
      benchmarking. This paper describes steps in the development of benchmarks for
      transition to adult care, often associated with low patient and family
      satisfaction. Qualitative data were collected through focus groups, workshops and
      interviews from 13 young people with long-term health conditions, 11 parents, 36
      professionals and 21 experts leading on transition within the United Kingdom.
      Transcripts were analysed using qualitative content analysis. For young people
      and their parents/carers to experience timely and effective transition, eight
      factors and their associated indicators of best practice were developed from the
      primary and secondary data and refined through an iterative process. We recommend
      their use to clinical teams to inform system level strategies as well as
      evaluation programmes. 

PMID- 26209174
TI  - McCune-Albright Syndrome: An Overview of Clinical Features.

PMID- 26209173
TI  - Integrating an EMR-based Transition Planning Tool for CYSHCN at a Children's
      Hospital: A Quality Improvement Project to Increase Provider Use and
      Satisfaction.
AB  - An electronic medical record (EMR)-based transition planning tool (TPT) designed
      to facilitate transition from pediatric to adult-based health care for youth (16
      25 years) with special health care needs was introduced at a large children's
      hospital. Activities to increase provider use were implemented in five plan-do
      study-act cycles. Overall, 22 of 25 (88%) consenting providers in four pediatric
      subspecialty services used the TPT during 303 patient encounters, with nurses and
      case-managers the top users and physicians the least likely users. Use was
      highest with intensive technical assistance and following the introduction of an
      upgraded tool. Provider satisfaction with the TPT and self-reported transition
      planning activities notably increased across the PDSA cycles.

PMID- 26209175
TI  - A microscale approach for simple and rapid monitoring of cell growth and lipid
      accumulation in Neochloris oleoabundans.
AB  - Due to the increasing environmental problems caused by the use of fossil fuels,
      microalgae have been spotlighted as renewable resources to produce biomass and
      biofuels. Therefore, the investigation of the optimum culture conditions of
      microalgae in a short time is one of the important factors for improving growth
      and lipid productivity. Herein, we developed a PDMS-based high-throughput
      screening system to rapidly and easily determine the optimum conditions for high
      density culture and lipid accumulation of Neochloris oleoabundans. Using the
      microreactor, we were able to find the optimal culture conditions of N.
      oleoabundans within 5 days by rapid and parallel monitoring growth and lipid
      induction under diverse conditions of light intensity, pH, CO2 and nitrate
      concentration. We found that the maximum growth rate (u max = 2.13 day(-1))
      achieved in the microreactor was 1.58-fold higher than that in a flask (u max =
      1.34 day(-1)) at the light intensity of 40 umol photons m(-2) s(-1), 5 % CO2
      (v/v), pH 7.5 and 7 mM nitrate. In addition, we observed that the accumulation of
      lipid in the microreactor was 1.5-fold faster than in a flask under optimum
      culture condition. These results show that the microscale approach has the great
      potential for improving growth and lipid productivity by high-throughput
      screening of diverse optimum conditions. 

PMID- 26209176
TI  - Mapping side chain interactions at protein helix termini.
AB  - BACKGROUND: Interactions that involve one or more amino acid side chains near the
      ends of protein helices stabilize helix termini and shape the geometry of the
      adjacent loops, making a substantial contribution to overall protein structure.
      Previous work has identified key helix-terminal motifs, such as Asx/ST N-caps,
      the capping box, and hydrophobic and electrostatic interactions, but important
      questions remain, including: 1) What loop backbone geometries are favoured by
      each motif? 2) To what extent are multi-amino acid motifs likely to represent
      genuine cooperative interactions? 3) Can new motifs be identified in a large,
      recent dataset using the latest bioinformatics tools? RESULTS: Three analytical
      tools are applied here to answer these questions. First, helix-terminal
      structures are partitioned by loop backbone geometry using a new 3D clustering
      algorithm. Next, Cascade Detection, a motif detection algorithm recently
      published by the author, is applied to each cluster to determine which sequence
      motifs are overrepresented in each geometry. Finally, the results for each motif
      are presented in a CapMap, a 3D conformational heatmap that displays the
      distribution of the motif's overrepresentation across loop geometries, enabling
      the rapid isolation and characterization of the associated side chain
      interaction. This work identifies a library of geometry-specific side chain
      interactions that provides a new, detailed picture of loop structure near the
      helix terminus. Highlights include determinations of the favoured loop geometries
      for the Asx/ST N-cap motifs, capping boxes, "big" boxes, and other hydrophobic,
      electrostatic, H-bond, and pi stacking interactions, many of which have not been
      described before. CONCLUSIONS: This work demonstrates that the combination of
      structural clustering and motif detection in the sequence space can efficiently
      identify side chain motifs and map them to the loop geometries which they
      support. Protein designers should find this study useful, because it identifies
      side chain interactions which are good candidates for inclusion in synthetic
      helix-terminal loops with specific desired geometries, since they are used in
      nature to support these geometries. The techniques described here can also be
      applied to map side chain interactions associated with other structural
      components of proteins such as beta and gamma turns.

PMID- 26209177
TI  - Activities of genes controlling sphingolipid metabolism in human fibroblasts
      treated with flavonoids.
AB  - Natural flavonoids such as genistein, kaempferol and daidzein were previously
      found to be able to reduce efficiency of glycosaminoglycan synthesis in cells of
      patients suffering from mucopolysaccharidoses, inherited metabolic diseases with
      often brain disease symptoms. This feature was employed to test these compounds
      as potential drugs for treatment other neuronopathic lysosomal storage disorders,
      in which errors in sphingolipid metabolism occur. In this report, on the basis of
      DNA microarray analyses and quantitative real time PCR experiments, we present
      evidence that these compounds modify expression of genes coding for enzymes
      required for metabolism of sphingolipids in human dermal fibroblasts (HDFa).
      Expression of several genes involved in sphingolipid synthesis was impaired by
      tested flavonoids. Therefore, it is tempting to speculate that they may be
      considered as potential drugs in treatment of LSD, in which accumulation of
      sphingolipids, especially glycosphingolipids, occurs. Nevertheless, further
      studies on more advances models are required to test this hypothesis and to
      assess a therapeutic potential for flavonoids in this group of metabolic brain
      diseases. 

PMID- 26209178
TI  - ?Doctor, habla espanol? Increasing the Supply and Quality of Language-Concordant
      Physicians for Spanish-Speaking Patients.

PMID- 26209180
TI  - Use of Interpreters by Physicians.

PMID- 26209179
TI  - Treatment with Dalteparin is Associated with a Lower Risk of Bleeding Compared to
      Treatment with Unfractionated Heparin in Patients with Renal Insufficiency.
AB  - BACKGROUND: Low molecular weight heparins (LMWHs) have been cautiously used in
      patients with chronic kidney disease (CKD) due to fear of accumulation.
      Dalteparin, however, has shown minimal tendency to accumulate in patients with
      CKD and may be safe to use in this patient population. OBJECTIVE: We compared the
      incidence of clinically significant bleeding in patients with CKD receiving
      therapeutic doses of dalteparin to that of patients with CKD receiving
      therapeutic doses of UFH. DESIGN: This was a retrospective cohort study.
      SUBJECTS: Inpatients with CKD (GFR < 60 ml/min) who were treated with therapeutic
      dalteparin or UFH were included in the study MAIN MEASURES: Primary outcome was
      major bleeding within 10 days of anticoagulation, identified by ICD-9 code and
      confirmed by chart review. Demographic characteristics, laboratory values,
      comorbidities, prior bleeding history and inpatient medications were extracted
      for each admission from the electronic medical record. Logistic regression models
      were created to examine the association between choice of anticoagulant and
      bleeding rates, after adjustment for demographic and clinical characteristics.
      KEY RESULTS: Dalteparin-treated patients were significantly less likely to
      experience a major bleed than patients treated with UFH (1.14 % vs. 3.49 %, p <
      0.001). The reduced likelihood of bleeding associated with dalteparin treatment
      remained significant after adjustment for patient characteristics (HR 0.39, 95 %
      CI: 0.21-0.70, p < 0.0001). A stratified analysis for subgroups with GFR< 30
      mL/min and with GFR between 30 and 60 mL/min showed that dalteparin was still
      associated with lower odds of bleeding compared to treatment with unfractionated
      heparin, but the difference was nonsignificant for GFR< 30 (HR 0.35, 95 % CI:
      0.11-1.15), even after adjustment (OR 0.37, 95 % CI: 0.11-1.22). CONCLUSION: In
      patients with CKD, treatment with therapeutic dose dalteparin was associated with
      lower rates of bleeding than treatment with unfractionated heparin. For patients
      with severe CKD (GFR< 30), dalteparin was shown to be at least as safe as
      unfractionated heparin.

PMID- 26209181
TI  - Perceptions of Risk of Developing Skin Cancer for Diverse Audiences: Enhancing
      Relevance of Sun Protection to Reduce the Risk.
AB  - Sixty-five percent of kidney transplant recipients (KTRs) develop squamous cell
      carcinoma (SCC). Perceptions of risk of developing skin cancer, amelioration of
      this risk with sun protection, and having choices among sun protection strategies
      may enhance sun protection use by KTRS, who are at greater risk than the general
      population. Thirty KTRs stratified among non-Hispanic Whites, non-Hispanic
      Blacks, and Hispanic/Latinos evaluated three versions of the interactive, web
      based, electronic sun protection program and suggested refinements. The sequence
      of content presentation prepared the participant to accept the credibility,
      accuracy, and relevance of the message. Beginning with informing participants
      that using sun protection reduces the chance of developing skin cancer made the
      information credible to KTRs. Showing skin cancer on all skin types and patient
      testimonials enhanced participants' awareness of their susceptibility to develop
      skin cancer and primed patients to receive their personal risk of developing skin
      cancer. Coupling presentation of knowledge about the benefits of sun protection
      in reducing the risk of developing skin cancer with the personal risk of getting
      the disease was essential to KTRs believing that they could influence their
      health outcome. 

PMID- 26209183
TI  - Molecular dynamics simulation studies of GSK-3beta ATP competitive inhibitors:
      understanding the factors contributing to selectivity.
AB  - Glycogen synthase kinase-3 is a constitutively acting, multifunctional serine
      threonine kinase, the role of which has been implicated in several physiological
      pathways and has emerged as a promising target for the treatment of type-II
      diabetes and Alzheimer's disease. In order to provide a detailed understanding of
      the origin of selectivity determinants of ATP competitive inhibitors, molecular
      dynamics simulations in combination with MM-PBSA binding energy calculations were
      performed using crystal structures of GSK-3beta and CDK-2 in complex with 12 ATP
      competitive inhibitors. Analysis of energy contributions indicate that
      electrostatic interaction energy dictates the selectivity of ATP competitive
      inhibitors against CDK-2. Key interactions as well as residues that potentially
      make a major contribution to the binding free energy were identified at the ATP
      binding site. This analysis stresses the need for the inhibitors to interact with
      Lys85, Thr138, and Arg141 in the binding site of GSK-3beta to show selectivity.
      The residue-wise energy decomposition analysis further suggested the additional
      role of Gln185 in determining the selectivity of maleimides. The results obtained
      in this study can be utilized to design new selective GSK-3 ATP competitive
      inhibitors. 

PMID- 26209182
TI  - Histopathological Evidence of Lymph Node Metastasis in Papillary Thyroid
      Carcinoma.
AB  - Prophylactic lymph node dissection is still controversial due to the potentially
      surgery-related morbidity in management of papillary thyroid carcinomas. So, some
      histopathological predictors for lymph node metastasis in thyroidectomy specimens
      may reveal importance. The objective of this study was to define
      histomorphological indicators of lymph node metastasis in the patients who had
      been performed thyroidectomy without lymph node dissection. Clinicopathological
      features of patients archived in Department of Pathology at Trakya University
      Medical Faculty were reviewed. A total of 211 patients who had been diagnosed as
      papillary carcinoma and had been performed total thyroidectomy/lobectomy with
      central/cervical lymph node dissection were included in the study. Clinical
      features (age, gender, preoperative/postoperative clinical, and laboratory
      findings) and histopathological features (histological variant, tumor size,
      focality, extrathyroidal extension, tumor border, lateral tubular growth,
      intraglandular dissemination, stromal and lymphocytic tumor response, lymphocytic
      thyroiditis, lymphovascular invasion, lymph node metastasis, number of metastatic
      lymph nodes, extranodal extension, size of the metastatic foci) were evaluated.
      Male gender, conventional variant, tumor size greater than 10 mm, multifocality,
      extrathyroidal extension, lateral tubular growth, intraglandular dissemination,
      lymphocytic and stromal tumor response, and absence of lymphocytic thyroiditis
      were predictive, and older age (>=45 years) and follicular variant PTC were
      protective for lymph node metastasis. In order to optimize the management of
      papillary thyroid carcinomas, pathologists should search for the clues of lymph
      node metastasis particularly intraglandular dissemination, lateral tubular
      growth, tumor border and lymphocytic/stromal tumor response, multifocality,
      concomitant lymphocytic thyroiditis besides the actual prognostic criteria
      especially in younger aged male patients. 

PMID- 26209184
TI  - Effect of antioxidants and light stabilisers on silver migration from nanosilver
      polyethylene composite packaging films into food simulants.
AB  - The effect of exposure time, temperature and food simulants, especially
      additives, on the release of silver from nanosilver-polyethylene composite films
      to food simulants was studied. Two different type of nanosilver-polyethylene
      composite films (with or without additives) were chosen to conduct the experiment
      with the aim of exploring the behaviour of silver migration. It was shown that
      the migration of silver into 50% ethanol at 40 and 70 degrees C was much less
      than that into 3% acetic acid. With the increase of exposure time and
      temperature, the release of silver increased. The migration even continued after
      a long exposure time (14 days at 20 degrees C, 10 days at 40 degrees C, and 6
      days at 70 degrees C respectively). Only about 0.150/00 of silver migrated from
      composite films with the additives into 3% acetic acid after 6 days of exposure
      at 70 degrees C, while about 1.3% of silver migrated from composite films that
      did not contain additives under the same conditions. This could be because the
      addition of the antioxidants and light stabilisers prevents silver from being
      oxidised, which is an important way for the release of silver.

PMID- 26209185
TI  - Insertion trauma and recovery of function after cochlear implantation: Evidence
      from objective functional measures.
AB  - Partial loss and subsequent recovery of cochlear implant function in the first
      few weeks following cochlear implant surgery has been observed in previous
      studies using psychophysical detection thresholds. In the current study, we
      explored this putative manifestation of insertion trauma using objective
      functional measures: electrically-evoked compound action potential (ECAP)
      amplitude-growth functions (ECAP amplitude as a function of stimulus level). In
      guinea pigs implanted in a hearing ear with good post-implant hearing and good
      spiral ganglion neuron (SGN) survival, consistent patterns of ECAP functions were
      observed. The slopes of ECAP growth functions were moderately steep on the day of
      implant insertion, decreased to low levels over the first few days after
      implantation and then increased slowly over several weeks to reach a relatively
      stable level. In parallel, ECAP thresholds increased over time after implantation
      and then recovered, although more quickly, to a relatively stable low level as
      did thresholds for eliciting a facial twitch. Similar results were obtained in
      animals deafened but treated with an adenovirus with a neurotrophin gene insert
      that resulted in good SGN preservation. In contrast, in animals implanted in deaf
      ears that had relatively poor SGN survival, ECAP slopes reached low levels within
      a few days after implantation and remained low. These results are consistent with
      the idea that steep ECAP growth functions require a healthy population of
      auditory nerve fibers and that cochlear implant insertion trauma can temporarily
      impair the function of a healthy SGN population.

PMID- 26209186
TI  - Contribution of the incudo-malleolar joint to middle-ear sound transmission.
AB  - The malleus and incus in the human middle ear are linked by the incudo-malleolar
      joint (IMJ). The mobility of the human IMJ under physiologically relevant
      acoustic stimulation and its functional role in middle-ear sound transmission are
      still debated. In this study, spatial stapes motions were measured during
      acoustic stimulation (0.25-8 kHz) in six fresh human temporal bones for two
      conditions of the IMJ: (1) normal IMJ and (2) IMJ with experimentally-reduced
      mobility. Stapes velocity was measured at multiple points on the footplate using
      a scanning laser Doppler vibrometry (SLDV) system, and the 3D motion components
      were calculated under both conditions of the IMJ. The artificial reduction of the
      IMJ mobility was confirmed by measuring the relative motion between the malleus
      and the incus. The magnitudes of the piston-like motion of the stapes increased
      with the reduced IMJ mobility above 2 kHz. The increase was frequency dependent
      and was prominent from 2 to 4 kHz and at 5.5 kHz. The magnitude ratios of the
      rocking-like motions to the piston-like motion were similar for both IMJ
      conditions. The frequency-dependent change of the piston-like motion after the
      reduction of the IMJ mobility suggests that the IMJ is mobile under
      physiologically relevant levels of acoustic stimulation, especially at
      frequencies above 2 kHz. 

PMID- 26209187
TI  - Effects of extracellular pH and hypoxia on the function and development of
      antigen-specific cytotoxic T lymphocytes.
AB  - The major effector cells for cellular adaptive immunity are CD8(+) cytotoxic T
      lymphocytes (CTLs), which can recognize and kill virus-infected cells and tumor
      cells. Although CTLs exhibit strong cytolytic activity against target cells in
      vitro, a number of studies have demonstrated that their function is often
      impaired within tumors. Nevertheless, CTLs can regain their cytotoxic ability
      after escaping from the tumor environment, suggesting that the milieu created by
      tumors may affect the function of CTLs. As for the tumor environment, the patho
      physiological situation present in vivo has been shown to differ from in vitro
      experimental conditions. In particular, low pH and hypoxia are the most important
      microenvironmental factors within growing tumors. In the present study, to
      determine the effect of these factors on CTL function in vivo, we examined the
      cytolytic activity of CTLs against their targets using murine CTL lines and the
      induction of these cells from memory cells under low pH or hypoxic conditions
      using antigen-primed spleen cells. The results indicated that both cytotoxic
      activity and the induction of functional CTLs were markedly inhibited under low
      pH. In contrast, in hypoxic conditions, although cytotoxic activity was almost
      unchanged, the induction of CTLs in vitro showed a slight enhancement, which was
      completely abrogated in low pH conditions. Therefore, antigen-specific CTL
      functions may be more vulnerable to low pH than to the oxygen concentration in
      vivo. The findings shown here provide new therapeutic approaches for controlling
      tumor growth by retaining CTL cytotoxicity through the maintenance of higher pH
      conditions. 

PMID- 26209188
TI  - The effectiveness and safety of modest exercise in Japanese patients with chronic
      kidney disease: a single-armed interventional study.
AB  - BACKGROUND: Poor physical ability and skeletal muscle wasting are common in
      chronic kidney disease (CKD) patients, who may experience a decline in daily
      activity and, in turn, increased mortality. The purpose of this study was to
      evaluate the effectiveness and safety of modest exercise in patients with stable
      CKD. METHODS: Forty-seven CKD patients were enrolled in a 6-month group program
      for aerobic and resistance exercise by self-training. Parameters of physical
      function and clinical laboratory markers, including renal function, were
      measured. RESULTS: The International Physical Activity Questionnaire score
      improved from a baseline of 36.6 +/- 13.8 to 40.1 +/- 14.8 after the exercise
      program (P < 0.001). The number of daily steps increased from 6141 +/- 2620 to
      7679 +/- 3026 (P < 0.001). We detected significant changes in the 30-s chair
      stand test (from 20.7 +/- 5.3 to 26.0 +/- 5.9 repetitions; P < 0.001), single
      foot standing test (from 53.0 +/- 44.3 to 68.4 +/- 43.0 s; P = 0.001) and 6-min
      walk (from 501.6 +/- 63.8 to 528.7 +/- 71.8 m; P = 0.02). Moreover, body weight,
      waist circumference, and blood pressure were significantly reduced. No
      significant deterioration was observed in the estimated glomerular filtration
      rate. Proteinuria significantly decreased in 21 patients. CONCLUSION: Our modest
      exercise program improved the physical performance of CKD patients without
      deterioration of renal function. These results suggest that exercise rather than
      excess rest should be recommended for CKD patients to avoid muscle wasting.

PMID- 26209189
TI  - An efficient and target-oriented sample enrichment method for preparative
      separation of minor alkaloids by pH-zone-refining counter-current chromatography.
AB  - An efficient and target-oriented sample enrichment method was established to
      increase the content of the minor alkaloids in crude extract by using the
      corresponding two-phase solvent system applied in pH-zone-refining counter
      current chromatography. The enrichment and separation of seven minor indole
      alkaloids from Uncaria rhynchophylla (Miq.) Miq. ex Havil(UR) were selected as an
      example to show the advantage of this method. An optimized two-phase solvent
      system composed of n-hexane-ethyl acetate-methanol-water (3:7:1:9, v/v) was used
      in this study, where triethylamine (TEA) as the retainer and hydrochloric acid
      (HCl) as the eluter were added at the equimolar of 10mM. Crude alkaloids of UR
      dissolved in the corresponding upper phase (containing 10mM TEA) were extracted
      twice with lower phase (containing 10mM TEA) and lower phase (containing 10mM
      HCl), respectively, the second lower phase extract was subjected to pH-zone
      refining CCC separation after alkalization and desalination. Finally, from 10g of
      crude alkaloids, 4g of refined alkaloids was obtained and the total content of
      seven target indole alkaloids was increased from 4.64% to 15.78%. Seven indole
      alkaloids, including 54mg isocorynoxeine, 21mg corynoxeine, 46mg
      isorhynchophylline, 35mg rhynchophylline, 65mg hirsutine, 51mg hirsuteine and
      27mg geissoschizine methylether were all simultaneously separated from 2.5g of
      refined alkaloids, with the purity of 86.4%, 97.5%, 90.3%, 92.1%, 98.5%, 92.3%,
      and 92.8%, respectively. The total content and purities of the seven minor indole
      alkaloids were tested by HPLC and their chemical structures were elucidated by
      ESI-HRMS and (1)H NMR. 

PMID- 26209190
TI  - Optimization of headspace solid phase microextraction for the analysis of
      microbial volatile organic compounds emitted by fungi: Application to historical
      objects.
AB  - The main goal of this work was to optimize the SPME sampling method for measuring
      microbial volatile organic compounds (MVOCs) emitted by active molds that may
      deteriorate historical objects. A series of artificially aged model materials
      that resemble those found in historical objects was prepared and evaluated after
      exposure to four different types of fungi. The investigated pairs consisted of:
      Alternaria alternata on silk, Aspergillus niger on parchment, Chaetomium globosum
      on paper and wool, and Cladosporium herbarum on paper. First of all, a selection
      of the most efficient SPME fibers was carried out as there are six different
      types of fibers commercially available. It was important to find a fiber that
      absorbs the biggest number and the highest amount of MVOCs. The results allowed
      establishing and selecting the DVB/CAR/PDMS fiber as the most effective SPME
      fiber for this kind of an analysis. Another task was to optimize the time of
      MVOCs extraction on the fiber. It was recognized that a time between 12 and 24h
      is adequate for absorbing a high enough amount of MVOCs. In the last step the
      temperature of MVOCs desorption in the GC injection port was optimized. It was
      found that desorption at a temperature of 250 degrees C allowed obtaining
      chromatograms with the highest abundances of compounds. To the best of our
      knowledge this work constitutes the first attempt of the SPME method optimization
      for sampling MVOCs emitted by molds growing on historical objects. 

PMID- 26209191
TI  - Improved separation and analysis of glycolipids by Iatroscan thin-layer
      chromatography-flame ionization detection.
AB  - We demonstrate improved power of Iatroscan thin layer chromatography/flame
      ionization detection (TLC-FID) technique for analysis of complex marine lipid
      mixture by developing protocol for the separation and analysis of glycolipids
      including sulfoquinovosyldiacylglycerols (SQDG), monogalactosyldiacylglycerols
      (MGDG) and digalactosyldiacylglycerols (DGDG). We have modified the common
      protocol used so far for the analysis of lipid classes by replacing the elution
      step which uses pure acetone for the elution of acetone mobile polar lipids, with
      the elution step containing chloroform-acetone (72:28, v:v) for separation of
      MGDG and DGDG. To separate SQDG from the complex lipid matrix we introduced
      solvent mixture acetone-chloroform-methanol-formic acid (33:33:33:0.6, v:v:v:v).
      Quantification of glycolipid classes was performed after calibration with
      glycolipid standards for the masses between 0.2 and 2.7-5.0MUg. With this new
      protocol we have successfully separated three glycolipids from the complex
      particulate lipid mixture of the seawater samples. Such an approach extends the
      power of existing protocol for the analysis of lipids which altogether ensure
      detection and quantification of 18 lipid classes what was demonstrated on
      seawater samples. This enables to gain a very broad system overview of the
      particularly complex environments as are seas, oceans and freshwaters. 

PMID- 26209192
TI  - Decoding glycome of Astragalus membranaceus based on pressurized liquid
      extraction, microwave-assisted hydrolysis and chromatographic analysis.
AB  - Carbohydrates in herbs are a relatively untapped source of new drugs and health
      beneficial ingredients. Their analysis has been developed as a novel aspect in
      quality control and herbal glycomics. In this study, glycome of Astragalus
      membranaceus was decoded based on optimized pressurized liquid extraction (PLE),
      microwave-assisted acidic hydrolysis (MAAH) and comprehensive chromatographic
      approaches. Twelve saccharides including sucrose, galacturonic acid, mannitol,
      fructose, rhamnose, ribose, arabinose, fucose, xylose, mannose, glucose and
      galactose were quantitatively analyzed by GC-MS and HPLC-CAD (charged aerosol
      detectors). Different columns, including Prevail Carbohydrate ES, XBridge Amide
      and CARBOSep CHO-820 CA for HPLC-CAD analysis, were compared for evaluation of
      oligosaccharides. The polysaccharides in water extract of Astragalus membranaceus
      were characterized by high performance size exclusive chromatography (HPSEC)
      combined with multiple angle light scattering detection (MALSD) and refractive
      index detection (RID). The results showed that A. membranaceus contained more
      than 108.5mgg(-1) free sucrose and small amounts of glucose 9.6-26.0mgg(-1) and
      fructose 8.7-22.9mgg(-1). While its polymeric carbohydrates were composed of
      glucose 71.0-162.3mgg(-1), galacturonic acid 52.0-113.4mgg(-1), arabinose 22.8
      54.4mgg(-1) and small amounts of galactose, rhamnose, xylose and mannose.
      CARBOSep CHO-820 CA showed its potential in simultaneously analyzing
      oligosaccharides and uronic acid, especially only the environment-friendly water
      mobile phase was used. HPSEC-MALSD-RID showed that there were three different
      molecular weight distributions of polysaccharides in A. membranaceus and the
      average molecular weight were 21901.1, 2038.5, and 353.4kDa. Hierarchical
      clustering analysis and principal component analysis demonstrated that A.
      membranaceus from different regions showed variations both in free and polymeric
      carbohydrates, which indicated that carbohydrates should be evaluated for the
      proper quality control of A. membranaceus. Rha, Ara, Xyl, Man and Gal were found
      to be the main elements for quality evaluation of polymeric carbohydrates in A.
      membranaceus by factor analysis. The strategy for decoding the glycome based on
      chromatographic approaches including GC-MS, HPLC-CAD and HPSEC-MALSD-RID after
      pressurized liquid extraction and microwave-assisted hydrolysis could be applied
      for carbohydrates profiling in herbs and beneficial for their quality control. 

PMID- 26209193
TI  - A novel approach to the simultaneous extraction and non-targeted analysis of the
      small molecules metabolome and lipidome using 96-well solid phase extraction
      plates with column-switching technology.
AB  - This study combines solid phase extraction (SPE) using 96-well plates with column
      switching technology to construct a rapid and high-throughput method for the
      simultaneous extraction and non-targeted analysis of small molecules metabolome
      and lipidome based on ultra-performance liquid chromatography quadrupole time-of
      flight mass spectrometry. This study first investigated the columns and
      analytical conditions for small molecules metabolome and lipidome, separated by
      an HSS T3 and BEH C18 columns, respectively. Next, the loading capacity and
      actuation duration of SPE were further optimized. Subsequently, SPE and column
      switching were used together to rapidly and comprehensively analyze the
      biological samples. The experimental results showed that the new analytical
      procedure had good precision and maintained sample stability (RSD<15%). The
      method was then satisfactorily applied to more widely analyze the small molecules
      metabolome and lipidome to test the throughput. The resulting method represents a
      new analytical approach for biological samples, and a highly useful tool for
      researches in metabolomics and lipidomics. 

PMID- 26209194
TI  - Ultramicro chitosan-assisted in-syringe dispersive micro-solid-phase extraction
      for flavonols from healthcare tea by ultra-high performance liquid
      chromatography.
AB  - A novel dispersive micro-solid-phase extraction (DMSPE) method using ultramicro
      chitosan as an adsorbent was proposed for the analysis of flavonols in Flos
      Sophorae tea, with detection by ultra-high performance liquid chromatography.
      Various parameters affecting the extraction recovery, including the concentration
      and viscosity of chitosan, extraction time and the pH of the sample solution were
      investigated and optimized. The optimized conditions were found to be 0.4MUg/mL
      of sorbent, pH of 7, an extraction time of 1.0min and 100MUL of methanol as the
      elution solvent. The DMSPE method showed excellent linearity (r(2)>0.99) with pre
      concentration factor values ranging from 23 to 77-fold. The limits of detection
      and quantification were 0.22-0.36ng/mL and 0.72-1.21ng/mL, respectively. This
      method was successfully applied to the analysis of flavonols in Flos Sophorae tea
      samples, and their recoveries were in the range of 95.2-102.4%. 

PMID- 26209195
TI  - A model free method for estimation of complicated adsorption isotherms in liquid
      chromatography.
AB  - Here we show that even extremely small variations in the adsorption isotherm can
      have a tremendous effect on the shape of the overloaded elution profiles and that
      the earlier in the adsorption isotherms the variation take place, the larger its
      impact on the shape of the elution profile. These variations are so small that
      they can be "hidden" by the discretization and in the general experimental noise
      when using traditional experimental methods, such as frontal analysis, to measure
      adsorption isotherms. But as the effects of these variations are more clearly
      visible in the elution profiles, the Inverse Method (IM) of adsorption isotherm
      estimation is an option. However, IM usually requires that one selects an
      adsorption isotherm model prior to the estimation process. Here we show that even
      complicated models might not be able to estimate the adsorption isotherms with
      multiple inflection points that small variations might give rise to. We therefore
      developed a modified IM that, instead of fixed adsorption isotherm models, uses
      monotone piecewise interpolation. We first validated the method with synthetic
      data and showed that it can be used to estimate an adsorption isotherm, which
      accurately predicts an extremely "strange" elution profile. For this case it was
      impossible to estimate the adsorption isotherm using IM with a fixed adsorption
      model. Finally, we will give an example of a real chromatographic system where
      adsorption isotherm with inflection points is estimated by the modified IM. 

PMID- 26209196
TI  - Two-dimensional ion chromatography for the separation of ionic organophosphates
      generated in thermally decomposed lithium hexafluorophosphate-based lithium ion
      battery electrolytes.
AB  - A two-dimensional ion chromatography (IC/IC) technique with heart-cutting mode
      for the separation of ionic organophosphates was developed. These analytes are
      generated during thermal degradation of three different commercially available
      SelectilyteTM lithium ion battery electrolytes. The composition of the
      investigated electrolytes is based on 1M lithium hexafluorophosphate (LiPF6)
      dissolved in ethylene carbonate/dimethyl carbonate (50:50wt%, LP30), ethylene
      carbonate/diethyl carbonate (50:50wt%, LP40) and ethylene carbonate/ethyl methyl
      carbonate (50:50wt%, LP50). The organophosphates were pre-separated from PF6(-)
      anion on the low capacity A Supp 4 column, which was eluted with a gradient step
      containing acetonitrile. The fraction containing analytes was retarded on a pre
      concentration column and after that transferred to the high capacity columns,
      where the separation was performed isocratically. Different stationary phases and
      eluents were applied on the 2nd dimension for the investigation of retention
      times, whereas the highly promising results were obtained with a high capacitive
      A Supp 10 column. The organophosphates generated in LP30 and LP40 electrolytes
      could be separated by application of an aqueous NaOH eluent providing fast
      analysis time within 35min. For the separation of the organophosphates of LP50
      electrolyte due to its complexity a NaOH eluent containing a mixture of
      methanol/H2O was necessary. In addition, the developed two dimensional IC method
      was hyphenated to an inductively coupled plasma mass spectrometer (ICP-MS) using
      aqueous NaOH without organic modifiers. This proof of principle measurement was
      carried out for future quantitative investigation regarding the concentration of
      the ionic organophosphates. Furthermore, the chemical stability of several ionic
      organophosphates in water and acetonitrile at room temperature over a period of
      10h was investigated. In both solvents no decomposition of the investigated
      analytes was observed and therefore water as solvent for dilution of samples was
      proved as suitable. 

PMID- 26209197
TI  - Azacitidine improves the T-cell repertoire in patients with myelodysplastic
      syndromes and acute myeloid leukemia with multilineage dysplasia.
AB  - Patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)
      with multilineage dysplasia show several immunological abnormalities. In this
      clinical setting, by combining flow cytometry and CDR3 spectratyping we monitored
      the kinetic of the T-cell repertoire during Azacitidine treatment, in order to
      explore its potential ability to reverse the immune derangement typical of these
      disorders. We firstly demonstrated by flow cytometry an increase in both CD4+ and
      CD8+ T-cell frequencies after starting treatment. Moreover, when monitored by
      spectratyping our patients showed significant changes in their T-cell receptor
      (TCR) CDR3 profiles, which were much more evident in helper T-cells. In fact, the
      frequency of BV (beta variable) subfamilies showing a skewed CDR3 profile
      significantly decreased from baseline to the following evaluations in CD4+ T
      cells (81% vs. 70%). This pattern was even more pronounced in patients responding
      to Azacitidine (90% vs. 61%). Our data show that the overall derangement of the T
      cell repertoire detectable in patients with MDS and AML with multilineage
      dysplasia gradually improves during Azacitidine treatment. These findings
      therefore suggest that Azacitidine could be potentially able, not only to restore
      the hematopoietic function, but also to reverse the immune derangement typical of
      these hematologic disorders. 

PMID- 26209198
TI  - The theory of planned behaviour is alive and well, and not ready to retire: a
      commentary on Sniehotta, Presseau, and Araujo-Soares.

PMID- 26209199
TI  - Some retirees remain active: a commentary on Sniehotta, Presseau and Araujo
      Soares.

PMID- 26209200
TI  - Extending not retiring the theory of planned behaviour: a commentary on
      Sniehotta, Presseau and Araujo-Soares.

PMID- 26209201
TI  - From studying the determinants of action to analysing its regulation: a
      commentary on Sniehotta, Presseau and Araujo-Soares.

PMID- 26209202
TI  - Time to retire the theory of planned behaviour? A commentary on Sniehotta,
      Presseau and Araujo-Soares.

PMID- 26209203
TI  - Will the new theories (and theoreticians!) please stand up? A commentary on
      Sniehotta, Presseau and Araujo-Soares.

PMID- 26209204
TI  - Mapping modifiable mechanisms in health promotion research: a commentary on
      Sniehotta, Presseau, and Araujo-Soares.

PMID- 26209205
TI  - Time to retire the theory of planned behaviour?: one of us will have to go! A
      commentary on Sniehotta, Presseau and Araujo-Soares.

PMID- 26209206
TI  - On retiring the TRA/TPB without retiring the lessons learned: a commentary on
      Sniehotta, Presseau and Araujo-Soares.

PMID- 26209207
TI  - Re-establishing momentum in theory development: a commentary on Sniehotta,
      Presseau and Araujo-Soares.

PMID- 26209208
TI  - A meta-analysis of the effects of measuring theory of planned behaviour
      constructs on behaviour within prospective studies.
AB  - Measurement reactivity effects, such as the mere measurement effect, have been
      proposed as a reason for behavioural changes in a number of theory of planned
      behaviour intervention studies. However, it is unclear whether such changes are
      the result of the mere measurement effect or of other artefacts of intervention
      study design. The aim of this study is to determine the size and direction of
      changes in health behaviours from baseline to follow-up in prospective studies
      using the theory of planned behaviour. Electronic databases were searched for the
      theory of planned behaviour studies which measured health behaviours at two or
      more time points. Change in behaviour was calculated for all studies. Sixty-six
      studies were included. Mean effect sizes across all studies were small and
      negative (d = -.03). Effect size was moderated by behaviour, behaviour type and
      follow-up length. Subgroup analyses showed significant decreases in socially
      undesirable behaviour (d = -.28), binge drinking (d = -.17), risk driving (d = 
      .20), sugar snack consumption (d = -.43) and sun-protective behaviour (d = -.18).
      Measurement of intention at baseline resulted in significant decreases in
      undesirable behaviour. Changes in undesirable behaviours reported in other
      studies may be the result of the mere measurement effect. 

PMID- 26209209
TI  - The effectiveness of motivational interviewing for health behaviour change in
      primary care settings: a systematic review.
AB  - Motivational interviewing (MI) is a patient-centred approach to behaviour change
      that was originally developed in the addiction field but has increasingly been
      applied to public health settings with a focus on health promotion. The purpose
      of this review was to examine the evidence base for MI interventions in primary
      care settings with non-clinical populations to achieve behaviour change for
      physical activity, dietary behaviours and/or alcohol intake. We also sought to
      explore the specific behaviour change techniques included in MI interventions
      within primary care. Electronic databases were searched for relevant articles and
      33 papers met inclusion criteria and were included. Approximately 50% of the
      included studies (n = 18) demonstrated positive effects in relation to health
      behaviour change. The efficacy of MI approaches is unclear given the
      inconsistency of MI descriptions and intervention components. Furthermore,
      research designs that do not isolate the effects of MI make it difficult to
      determine the effectiveness of such approaches. We offer a number of
      recommendations for researchers and practitioners seeking to include MI within
      behaviour change interventions to help improve the quality of the research and
      the effectiveness of MI-based interventions within primary care settings. 

PMID- 26209210
TI  - Mindfulness-based stress reduction for people living with HIV/AIDS: preliminary
      review of intervention trial methodologies and findings.
AB  - In the context of successful antiretroviral therapy (ART) for the management of
      HIV infection, the harmful effects of stress remain a significant threat. Stress
      may increase viral replication, suppress immune response, and impede adherence to
      ART. Stressful living conditions of poverty, facing a chronic life-threatening
      illness and stigma all exacerbate chronic stress in HIV-affected populations.
      Stress-reduction interventions are urgently needed for the comprehensive care of
      people living with HIV. Mindfulness-based stress reduction (MBSR) is one approach
      that has shown promise as an intervention for patients facing other medical
      conditions for reducing disease progression, psychological distress and
      maladaptive behaviours. In this systematic review, we identified 11 studies that
      have examined MBSR as an intervention for HIV-positive populations. Of the
      studies, six were randomised designs, one was a quasi-experimental design, and
      the remaining four were pre- and post-test designs. The preliminary outcomes
      support MBSR to decrease emotional distress with mixed evidence for impact on
      disease progression. Effect sizes were generally small to moderate in magnitude.
      The early findings from this emerging literature must be considered preliminary
      and support moving forward with more rigorous controlled trials, evaluated with
      objective assessments in longer-term follow-ups to determine the efficacy of MBSR
      for people living with HIV. 

PMID- 26209211
TI  - Efficacy of physical activity interventions in post-natal populations: systematic
      review, meta-analysis and content coding of behaviour change techniques.
AB  - This systematic review and meta-analysis reports the efficacy of post-natal
      physical activity change interventions with content coding of behaviour change
      techniques (BCTs). Electronic databases (MEDLINE, CINAHL and PsychINFO) were
      searched for interventions published from January 1980 to July 2013. Inclusion
      criteria were: (i) interventions including >=1 BCT designed to change physical
      activity behaviour, (ii) studies reporting >=1 physical activity outcome, (iii)
      interventions commencing later than four weeks after childbirth and (iv) studies
      including participants who had given birth within the last year. Controlled
      trials were included in the meta-analysis. Interventions were coded using the 40
      item Coventry, Aberdeen & London - Refined (CALO-RE) taxonomy of BCTs and study
      quality assessment was conducted using Cochrane criteria. Twenty studies were
      included in the review (meta-analysis: n = 14). Seven were interventions
      conducted with healthy inactive post-natal women. Nine were post-natal weight
      management studies. Two studies included women with post-natal depression. Two
      studies focused on improving general well-being. Studies in healthy populations
      but not for weight management successfully changed physical activity.
      Interventions increased frequency but not volume of physical activity or walking
      behaviour. Efficacious interventions always included the BCTs 'goal setting
      (behaviour)' and 'prompt self-monitoring of behaviour'. 

PMID- 26209212
TI  - A systematic review of the factors associated with delays in medical and
      psychological help-seeking among men.
AB  - Despite a growing literature on the factors associated with men's low rates of
      medical and psychological help-seeking, a systematic review of these is missing.
      Such an overview can help to inform health psychologists of the barriers to the
      performance of adaptive health behaviours, such as prompt help-seeking, and could
      inform theoretical advancements and the development of targeted interventions to
      facilitate prompt help-seeking among men. We systematically reviewed quantitative
      and qualitative empirical papers on factors associated with delays in men's
      medical and psychological help-seeking. The Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and we
      used the databases PsycINFO, Medline, Embase and PsycARTICLES (with keywords:
      men/male*/gender*, help*/seek* and health*/service*/utili*[sation]) for papers in
      English. 41 citations (amounting to 21,787 participants aged 15-80 + ) met the
      inclusion criteria. Approximately half of these used qualitative methodologies
      (i.e., semi-structured interviews and focus groups), while half used quantitative
      methodologies (i.e., questionnaires). We identify a number of recurring
      cognitive, emotional, health-service related and socio-demographic help-seeking
      factors/predictors from the 41 papers. Of these, the most prominent barriers to
      help-seeking were disinclination to express emotions/concerns about health,
      embarrassment, anxiety and fear, and poor communication with health-care
      professionals. 

PMID- 26209213
TI  - Development of a multimorbidity index: Impact on quality of life using a
      rheumatoid arthritis cohort.
AB  - OBJECTIVE: To develop a multimorbidity index (MMI) based on health-related
      quality of life (HRQol). METHODS: The index was developed in an observational RA
      cohort. In all, 40 morbidities recommended as core were identified using ICD-9
      codes. MMIs of two types were calculated: one by enumerating morbidities
      (MMI.count) and the other by weighting morbidities based on their association
      with HRQol as assessed by EQ-5D in multiple linear regression analysis (using
      beta-coefficients; MMI.weight). MMIs were compared to the Charlson comorbidity
      index (CCI) and externally validated in an international RA cohort (COMORA
      Study). RESULTS: In all, 544 out of 876 patients were multimorbid. MMI.count was
      in the range 1-16 (median = 2) and MMI.weight in the range 0-38 (median = 1).
      Both indices were more strongly associated with EQ-5D than CCI (Spearman:
      MMI.count = -0.20, MMI.weight = -0.26, and CCI = -0.10; p < 0.01). R(2) obtained
      by linear regression using EQ-5D as a dependent variable and various indices as
      independent variables, adjusted for age and gender, was the highest for MMI
      (R(2): MMI.count = 0.05, MMI.weight = 0.11, and CCI = 0.02). When accounting for
      clinical disease activity index (CDAI) R(2) increased: MMI.count = 0.18,
      MMI.weight = 0.22, and CCI = 0.17, still showing higher values of MMI compared
      with CCI. External validation in different RA cohorts (COMORA, n = 3864) showed
      good performance of both indices (linear regression including age, gender, and
      disease activity R(2) = 0.30 for both MMIs). CONCLUSION: In our cohort, MMI based
      on EQ-5D performed better than did CCI. Findings were reproducible in another
      large RA cohort. Not much improvement was gained by weighting; therefore a simple
      counted index could be useful to control for the effect of multimorbidity on
      patient's overall well-being.

PMID- 26209216
TI  - Echocardiography of a young man with dyspnoea. Subaortic membrane.

PMID- 26209217
TI  - [Not Available].

PMID- 26209218
TI  - Postoperative pyoderma gangrenosum (PG): the Mayo Clinic experience of 20 years
      from 1994 through 2014.
AB  - BACKGROUND: Postoperative pyoderma gangrenosum (PG) is a neutrophilic dermatosis
      characterized by the development of PG-type lesions within surgical sites.
      OBJECTIVE: We sought to characterize postoperative PG as a distinct subtype of PG
      for earlier recognition and prevention of improper therapy. METHODS: We conducted
      a retrospective chart review of patients with nonperistomal postoperative PG at
      Mayo Clinic from 1994 to 2014.x RESULTS: Eighteen patients had postoperative PG
      with an average age of 58 years. Fifteen (83%) were female. Among patients with
      postoperative PG, 4 (22%) had an associated systemic disease traditionally
      associated with PG. Sites of postoperative PG included 7 breast (38%), 7 abdomen
      (38%), 1 back, 1 shoulder, 1 ankle, and 1 scrotum, witxxh breast reconstruction
      being the most common surgery. The average time to symptoms was 11 days. No
      patients had a fever. Eight (44%) had documented anemia and 5 (27%) had
      leukocytosis. Antibiotics and systemic corticosteroids were initiated in 10 (56%)
      and 14 (83%), respectively. Debridement was done in 11 (61%) patients.
      LIMITATIONS: Small sample size and retrospective study are limitations.
      CONCLUSION: Postoperative PG is a rare surgical complication with predilection
      for the breast and abdomen of females and has less association with systemic
      disease than idiopathic PG. Early recognition may prevent unnecessary
      debridements and morbidity.

PMID- 26209219
TI  - Combined cutaneous tumors with a melanoma component: A clinical, histologic, and
      molecular study.
AB  - BACKGROUND: The histogenesis and clinical behavior of combined cutaneous tumors
      (CCTs) in which the mesenchymal component consists of melanoma remain unclear.
      OBJECTIVE: We sought to characterize the clinical, histologic, and molecular
      findings in CCTs with an epithelial and a melanoma component. METHODS: We
      retrospectively reviewed the records from 2 institutions for CCTs. Fluorescence
      in situ hybridization was performed to assess chromosomal copy number alterations
      in both components. RESULTS: Sixteen CCTs were included. The most common subtype
      was the squamomelanocytic tumor (11), followed by the basomelanocytic tumor (3)
      and the trichoblastomelanoma (2). CCTs were more common in men (87%), on the head
      and neck (57%), and had extensive solar elastosis (81%). The median follow-up was
      25 months (range, 8-167 months). One case had an adverse outcome. Fluorescence in
      situ hybridization revealed chromosomal alterations in approximately 55% of the
      cases. Five cases showed chromosomal gains only in the melanocytic component. One
      case showed 11q13 gains in both the epithelial and melanocytic components.
      LIMITATIONS: Our study is retrospective and the sample is small. CONCLUSIONS: The
      low incidence of adverse outcomes suggests that CCT may be more indolent than
      noncombined tumors. 11q13 amplification in both components supports the theory of
      dual differentiation from a common progenitor cell.

PMID- 26209220
TI  - Immunosuppression is an independent prognostic factor associated with aggressive
      tumor behavior in cutaneous melanoma.
AB  - BACKGROUND: A number of factors other than those identified by the American Joint
      Committee on Cancer (AJCC) may have prognostic significance in the evaluation of
      melanoma. OBJECTIVE: We sought to evaluate commonly recorded clinical features
      potentially associated with aggressive melanoma. METHODS: We conducted a
      retrospective case-control study. We included patients given a diagnosis of
      cutaneous melanoma with at least 5 years of follow-up or documented metastases.
      Patients were divided into nonaggressive and aggressive groups. Univariate and
      multivariate statistical analyses were performed to evaluate the association of
      multiple clinical and histologic parameters and metastases. RESULTS: We included
      141 patients. Significant prognostic factors in univariate analysis associated
      with nonaggressive disease included history of dysplastic nevus syndrome and
      ABCDE criteria. Significant factors in univariate analysis associated with
      aggressive disease included age and immunosuppression. Only age and
      immunosuppression remained significant in multivariate analysis when controlled
      across statistically significant histologic variables from AJCC. LIMITATIONS: The
      study is retrospective and has a small sample size. CONCLUSION: Older patients
      and those with a history of immunosuppression may be at higher risk for
      aggressive disease and should be closely monitored after an initial diagnosis of
      melanoma.

PMID- 26209221
TI  - Medical Nutrition Therapy for Patients With Advanced Systemic Sclerosis (MNT
      PASS): A Pilot Intervention Study.
AB  - BACKGROUND: The objective of this study was to demonstrate the feasibility and
      associations with short-term outcomes of a medical nutrition therapy (MNT)
      intervention in patients with systemic scleroderma (SSc). MATERIALS AND METHODS:
      Eighteen patients with SSc, gastrointestinal (GI) involvement, and unintentional
      weight loss were consented and recruited for a 6-week MNT intervention, in
      addition to their usual medical management. MNT emphasized increased calorie and
      protein intake, modified textures, and lifestyle modifications. Symptoms,
      anthropometrics, diet (24-hour recall), and body composition (dual-energy x-ray
      absorptiometry) were assessed pre- and postintervention. Sarcopenia was defined
      as appendicular lean height (ALH) for women <5.45 kg/m2 and for men <7.26 kg/m2.
      Descriptive, parametric, and nonparametric statistics were conducted. RESULTS:
      Participants (n = 18) were predominantly white (78%), female (89%), malnourished
      (83%), and 51.3 +/- 11.0 years of age with a body mass index of 22.6 +/- 6.7
      kg/m2. Significant decreases in nutrition symptom scores (12.8 vs 7.6, P < .05)
      and improvements in ALH (5.6 +/- 0.8 vs 5.8 +/- 0.8 kg/m2, respectively; P = .05)
      occurred pre- vs postintervention, respectively (n = 14). Sarcopenia was observed
      in 54% of participants at baseline and 39% at follow-up ( P = .02). Caloric
      intake (1400 vs 1577 kcal/d, P = .12) and macronutrient distribution (ie, % fat,
      protein, carbohydrate) did not change significantly pre- vs postintervention,
      respectively. CONCLUSIONS: Individually tailored MNT can improve symptom burden
      and potentially ALH in patients with SSc involving the GI tract. This study
      underscores the clinical potential of multidisciplinary patient management and
      the need for larger nutrition intervention trials of longer duration in these
      patients.

PMID- 26209222
TI  - Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of
      Dementia.
AB  - OBJECTIVE: To identify clusters of patients with incident mild cognitive
      impairment (MCI) based on their neuropsychiatric symptoms (NPS) and to examine
      the risk of progression to dementia based on these clusters. METHODS: In this
      cohort study with a median of 2 years of follow-up from the National Alzheimer's
      Coordinating Center, 540 patients with MCI at least 60 years old with complete
      data and follow-up were studied. Latent class analysis was used to identify
      clusters of patients based on their NPS, and Cox proportional hazards models were
      used to examine risk of progression to dementia based on clusters. Incident MCI
      was defined as a participant having MCI at a current visit but having been
      cognitively normal at his or her previous (yearly) visit. The Neuropsychiatric
      Inventory Questionnaire assessed the presence of 12 neuropsychiatric behavioral
      domains. RESULTS: Three clusters were identified: a severe cluster (agitation,
      anxiety, apathy, nighttime behaviors, inhibition), an affective cluster
      (depression, anxiety, irritability, nighttime behaviors), and an asymptomatic
      cluster. The prevalence of each class was 56% for the asymptomatic class followed
      by the affective class (37%) and finally the severe class (7%). Compared with the
      asymptomatic class, the severe class had more than twice the hazard of
      progression to dementia (2.69; 95% CI: 1.12-2.70) and the affective class had
      over 1.5 times the hazard of progression to dementia (1.79; 95% CI: 1.12-2.70).
      CONCLUSION: Among persons with incident MCI, patterns of NPS may increase the
      likelihood of progression to dementia. Implications for early detection and
      treatment are discussed.

PMID- 26209223
TI  - Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample
      of Women at Risk for Alzheimer Disease.
AB  - OBJECTIVE: Use of estrogen-based hormone therapy (HT) as a protection from
      cognitive decline and Alzheimer disease (AD) is controversial, although
      cumulative data support HT use when initiated close to menopause onset with
      estrogen formulations containing 17beta-estradiol preferable to conjugated equine
      estrogen formulations. Little is known regarding specific populations of women
      who may derive benefit from HT. METHODS: Women with heightened risk for AD (aged
      49-69), all of whom were taking HT for at least 1 year and most of whom initiated
      HT close to menopause onset, underwent cognitive assessment followed by
      randomization to continue or discontinue HT. Assessments were repeated at 2 years
      after randomization. RESULTS: Women who continued HT performed better on
      cognitive domains composed of measures of verbal memory and combined attention,
      working memory, and processing speed measures. Women who used 17beta-estradiol
      versus conjugated equine estrogen, whether randomized to continue or discontinue
      HT, showed better verbal memory performance at the 2-year follow-up assessment.
      An interaction was also found with HT randomization and family history of AD in a
      first-degree relative. All female offspring of patients with AD declined in
      verbal memory; however, women who continued HT declined less than women who
      discontinued HT. Women without a first-degree relative with AD showed verbal
      memory improvement (likely because of practice effects) with continuance and
      declined with discontinuance of HT. CONCLUSION: Continuation of HT use appears to
      protect cognition in women with heightened risk for AD when initiated close to
      menopause onset.

PMID- 26209224
TI  - Role of Executive Dysfunction and Dysexecutive Behavior in Late-Life Depression
      and Disability.
AB  - OBJECTIVE: Both executive dysfunction (ED), measured by performance-based tasks,
      and dysexecutive behavior (DB), measured by behavioral rating scales, contribute
      to late-life depression and comorbid disability. There is a modest positive
      association of ED and DB, but less is known about their relative contributions to
      core aspects of neuropsychiatric conditions and whether they provide unique or
      redundant information. METHODS: Latent variable analyses were applied to ED, DB,
      depression, and disability data from 220 older patients with major depression and
      ED who had been enrolled in a psychosocial treatment study of depression. ED
      measures included the Trail Making Test, part B, Stroop Color Word Interference
      Test, and Hopkins Verbal Learning Test-Trail 1. The ED scale from the Frontal
      Systems Behavior Scale, self and other-rated, served as the ratings-based measure
      of DB. RESULTS: The measurement model, with all four latent variables related to
      one another, demonstrated good fit (RMSEA=0.06). In the structural models, DB was
      associated with both depression (beta=0.61) and disability (beta=0.42), whereas
      ED was associated with depression (beta=0.43) but not disability (beta=0.16).
      Social problem-solving accounted for 49% of the influence of DB on late-life
      depression, whereas ED was not related to social problem-solving. CONCLUSION: ED
      and the lesser studied DB measures offer unique and complementary information. DB
      was robustly associated with late-life depression and disability. Patients with
      depression and ED may be more likely to develop disability when they exhibit DB
      and social problem-solving difficulties.

PMID- 26209225
TI  - A refined QSAR model for prediction of chemical asthma hazard.
AB  - BACKGROUND: A previously developed quantitative structure-activity relationship
      (QSAR) model has been extern ally validated as a good predictor of chemical
      asthma hazard (sensitivity: 79-86%, specificity: 93-99%). AIMS: To develop and
      validate a second version of this model. METHODS: Learning dataset asthmagenic
      chemicals with molecular weight (MW) <1 kDa were identified from reports
      published in the peer-reviewed literature before the end of 2012. Control
      chemicals for which no reported case(s) of occupational asthma had been
      identified were selected at random from UK and US occupational exposure limit
      tables. MW banding was used in an attempt to categorically match the control
      group for MW distribution of the asthmagens. About 10% of chemicals in each MW
      category were excluded for use as an external validation set. An independent
      researcher utilized a logistic regression approach to compare the molecular
      descriptors present in asthmagens and controls. The resulting equation generated
      a hazard index (HI), with a value between zero and one, as an estimate of the
      probability that the chemical had asthmagenic potential. The HI was determined
      for each compound in the external validation set. RESULTS: The model development
      sets comprised 99 chemical asthmagens and 204 controls. The external validation
      showed that using a cut-point HI of 0.39, 9/10 asthmagenic (sensitivity: 90%) and
      23/24 non-asthmagenic (specificity: 96%) compounds were correctly predicted. The
      new QSAR model showed a better receiver operating characteristic plot than the
      original. CONCLUSIONS: QSAR refinement by iteration has resulted in an improved
      model for the prediction of chemical asthma hazard.

PMID- 26209227
TI  - Risk factors for postoperative pneumonia after lung cancer surgery and impact of
      pneumonia on survival.
AB  - OBJECTIVE: Little is known about risk factors and prognosis for postoperative
      pneumonia (POP) in patients undergoing therapeutic lung cancer (LC) surgery.
      METHODS: We followed a nationwide population-based cohort of 7479 patients with
      LC surgery in Denmark 1995-2011. We used logistic regression analysis to examine
      risk factors for POP within 30 days after surgery. Subsequent survival in
      patients with POP was analyzed with Cox regression. RESULTS: We identified 268
      (3.6%) patients with POP. Important risk factors included advanced age (age >=80
      years: (adjusted odds ratio [aOR] = 3.64; 95% CI: 2.17-6.12) as compared to
      patients aged 50-59 years), previous pneumonia (aOR = 2.68; 95% CI: 2.02-3.56),
      obesity (aOR = 1.91; 95% CI: 0.99-3.69), chronic pulmonary disease (aOR = 1.90;
      95% CI: 1.40-2.57), alcoholism (aOR = 1.56; 95% CI: 0.81-3.01), and atrial
      fibrillation (aOR = 1.42; 95% CI: 0.82-2.45). Overall thoracoscopic surgery
      halved the risk of POP and the highest risk of POP was seen in pneumonectomy
      performed in open thoracotomy. Among patients surviving the 30-day postoperative
      period, 31-365 day mortality was 21.6% in POP patients vs. 16.8% in non-POP
      patients, and 1-5-year mortality was 62.2% vs. 53.0%. Adjusted 31-365 day hazard
      ratio (HR) of death with POP was 1.31 (95% CI: 1.00-1.73), and 1-5 year HR was
      1.22 (95% CI 0.98-1.53). CONCLUSION: Major risk factors for POP following LC
      surgery are advanced age, previous pneumonia, obesity, chronic pulmonary disease,
      alcoholism, and atrial fibrillation. POP is a clinical marker for decreased LC
      survival.

PMID- 26209226
TI  - GTSE1 expression represses apoptotic signaling and confers cisplatin resistance
      in gastric cancer cells.
AB  - BACKGROUND: Platinum based therapy is commonly used in the treatment of advanced
      gastric cancer. However, resistance to chemotherapy is a major challenge that
      causes marked variation in individual response rate and survival rate. In this
      study, we aimed to identify the expression of GTSE1 and its correlation with
      cisplatin resistance in gastric cancer cells. METHODS: Methylation profiling was
      carried out in tissue samples from gastric cancer patients before undergoing
      neoadjuvent therapy using docetaxel, cisplatin and 5FU (DCX) and in gastric
      cancer cell lines. The correlation between GTSE1 expression and methylation in
      gastric cancer cells was determined by RT-PCR and MSP respectively. GTSE1
      expression was knocked-down using shRNA's and its effects on cisplatin
      cytotoxicity and cell survival were detected by MTS, proliferation and clonogenic
      survival assays. Additionally, the effect of GTSE1 knock down in drug induced
      apoptosis was determined by western blotting and apoptosis assays. RESULTS: GTSE1
      exhibited a differential methylation index in gastric cancer patients and in cell
      lines that correlated with DCX treatment response and cisplatin sensitivity,
      respectively. In-vitro, GTSE1 expression showed a direct correlation with
      hypomethylation. Interestingly, Cisplatin treatment induced a dose dependent up
      regulation as well as nuclear translocation of GTSE1 expression in gastric cancer
      cells. Knock down of GTSE1 enhanced cisplatin cytotoxity and led to a significant
      reduction in cell proliferation and clonogenic survival. Also, loss of GTSE1
      expression caused a significant increase in P53 mediated apoptosis in cisplatin
      treated cells. CONCLUSION: Our study identifies GTSE1 as a biomarker for
      cisplatin resistance in gastric cancer cells. This study also suggests the
      repressive role of GTSE1 in cisplatin induced apoptosis and signifies its
      potential utility as a therapeutic target for better clinical management of
      gastric cancer patients.

PMID- 26209228
TI  - Cissampelos sympodialis Eichl. (Menispermaceae), a medicinal plant, presents
      antimotility and antidiarrheal activity in vivo.
AB  - BACKGROUND: Cissampelos sympodialis (Menispermaceae), known as "Milona" has a
      specific verified medicinal use for the treatment of diarrhea and respiratory
      tract diseases. This work aims to evaluate the antimotility and antidiarrheal
      activity of crude ethanolic extract (EtOHE-Cs), and the total alkaloid fraction
      (TAF-Cs) obtained from aerial parts of C. sympodialis. METHODS: Normal intestinal
      transit and gastric emptying were used to evaluate antimotility activity. Castor
      oil-induced diarrhea and castor oil-induced enteropooling were used to evaluate
      antidiarrheal activity. RESULTS: The results indicated that EtOHE-Cs has no
      antimotility activity, but did demonstrate antidiarrheal activity (at 500 mg/kg),
      and this activity is related to reduction of intestinal fluid accumulation. The
      TAF-Cs (at 250 and 500 mg/kg) showed antidiarrheal activity by reducing
      gastrointestinal motility (gastric emptying and normal intestinal transit).
      CONCLUSIONS: The antidiarrheal activity of C. sympodialis can be attributed to
      the chemical compounds already isolated and quantified in this species, mainly
      alkaloids.

PMID- 26209229
TI  - Two COWP-like cysteine rich proteins from Eimeria nieschulzi (coccidia,
      apicomplexa) are expressed during sporulation and involved in the sporocyst wall
      formation.
AB  - BACKGROUND: The family of cysteine rich proteins of the oocyst wall (COWPs)
      originally described in Cryptosporidium can also be found in Toxoplasma gondii
      (TgOWPs) localised to the oocyst wall as well. Genome sequence analysis of
      Eimeria suggests that these proteins may also exist in this genus and led us to
      the assumption that these proteins may also play a role in oocyst wall formation.
      METHODS: In this study, COWP-like encoding sequences had been identified in
      Eimeria nieschulzi. The predicted gene sequences were subsequently utilized in
      reporter gene assays to observe time of expression and localisation of the
      reporter protein in vivo. RESULTS: Both investigated proteins, EnOWP2 and EnOWP6,
      were expressed during sporulation. The EnOWP2-promoter driven mCherry was found
      in the cytoplasm and the EnOWP2, respectively EnOWP6, fused to mCherry was
      initially observed in the extracytoplasmatic space between sporoblast and oocyst
      wall. This, so far unnamed compartment was designated as circumplasm. Later, the
      mCherry reporter co-localised with the sporocyst wall of the sporulated oocysts.
      This observation had been confirmed by confocal microscopy, excystation
      experiments and IFA. Transcript analysis revealed the intron-exon structure of
      these genes and confirmed the expression of EnOWP2 and EnOWP6 during sporogony.
      CONCLUSIONS: Our results allow us to assume a role, of both investigated EnOWP
      proteins, in the sporocyst wall formation of E. nieschulzi. Data mining and
      sequence comparisons to T. gondii and other Eimeria species allow us to
      hypothesise a conserved process within the coccidia. A role in oocyst wall
      formation had not been observed in E. nieschulzi.

PMID- 26209230
TI  - Early Vitrectomy for Spontaneous, Fundus-Obscuring Vitreous Hemorrhage.
AB  - PURPOSE: To examine the visual outcomes of early intervention in the setting of
      fundus-obscuring vitreous hemorrhage (VH) presumed to be due to posterior
      vitreous detachment. DESIGN: Retrospective comparative case series. METHODS: All
      eyes that presented with a fundus-obscuring VH, defined as vision of 20/400 or
      worse and requiring a B-scan at presentation from 2003 to 2013, were evaluated.
      Eyes with any history of retinopathy, macular degeneration, recent trauma,
      presentation greater than 2 weeks after onset of symptoms, or follow-up of less
      than 2 months were excluded. The main outcome measure studied was final best
      corrected visual acuity (BCVA) as dependent on the time to surgery. RESULTS:
      Ninety-two eyes met inclusion criteria with a mean follow-up of 490 days. Initial
      BCVA was logMAR 2.218 (Snellen equivalent 20/3000-20/4000, range 20/400-light
      perception); final BCVA was 0.318 (Snellen equivalent of 20/40-20/50, range 20/20
      light perception, P < .001). Fifty-six patients (60.8%) had either a retinal tear
      or a retinal detachment. Patients who underwent surgery within 1 week had no
      significant improvement over all others; however, a significant improvement was
      found when comparing early vs delayed surgery groups (P < .05). There was a
      significantly increased risk of developing a macula-off retinal detachment in
      patients who did not undergo surgery within 1 week of presentation. CONCLUSIONS:
      Early surgical intervention results in similar visual outcomes compared to a
      conservative approach. However, early intervention significantly reduces the
      incidence of severe vision loss related to macula-involving retinal detachment.
      This study highlights the importance of close follow-up given the high risk of
      retinal detachment in fundus-obscuring vitreous hemorrhage.

PMID- 26209231
TI  - Lacquer Cracks and Perforating Scleral Vessels in Pathologic Myopia: A Possible
      Causal Relationship.
AB  - PURPOSE: To describe a possible causal association between the position of
      perforating scleral vessels and the position of lacquer cracks in eyes with
      pathologic myopia. DESIGN: Retrospective case series. METHODS: Medical records
      and multimodal imaging results, including confocal scanning laser ophthalmoscopy
      and spectral-domain optical coherence tomography, were reviewed from patients
      with lacquer cracks secondary to pathologic myopia who presented between 2010 and
      2014 to 2 institutions. Main outcome measures were the prevalence of perforating
      scleral vessels at the site of the lacquer crack, the position of the lacquer
      crack within the macula, and the relationships between perforating scleral
      vessels and retinal-choroidal structures. RESULTS: A total of 35 eyes of 30
      patients with lacquer cracks were included. The average number of lacquer cracks
      was 1.2 +/- 0.5/eye and in 37 out of 45 lacquer cracks (82%) retrobulbar vessels
      were found to perforate the sclera at the site of the lacquer crack. Lacquer
      cracks were more prevalent in the central macula (51%) than in the nasal (19%),
      temporal (14%), inferior (11%), and superior macula (5%) (P = .001). Transverse
      en face images through the area of lacquer cracks were available for 8 cases and
      clearly depicted the perforating vessel's course through the sclera and its
      termination in the choroid, directly beneath the lacquer cracks. CONCLUSIONS:
      Perforating scleral vessels are often present beneath the site at which lacquer
      cracks form in pathologic myopia. We hypothesize that scleral expansion at the
      location of these perforating vessels may play a role in the formation of lacquer
      cracks.

PMID- 26209232
TI  - Clinical Outcomes Following Implantation of Diffractive Multifocal Intraocular
      Lenses With Varying Add Powers.
AB  - PURPOSE: To compare clinical outcomes after implantation of TECNIS diffractive
      multifocal intraocular lenses (IOLs) with different add powers. DESIGN:
      Prospective, comparative, interventional case series. METHODS: Subjects underwent
      cataract extraction and diffractive multifocal IOL implant. Subjects had an
      additional add power of +2.75 diopters (D) (Group 1, 23 eyes), +3.25 D (Group 2,
      21 eyes), or +4.00 D (Group 3, 21 eyes). Evaluations were performed 1 and 3
      months following cataract surgery, including measurement of monocular uncorrected
      distance visual acuity (UDVA), refractive error (manifest refraction [MR]), and
      monocular uncorrected near visual acuity (UNVA) at 33, 40, and 50 cm. At 3
      months, internal aberrations and contrast sensitivity were evaluated and subjects
      completed a questionnaire on outcomes satisfaction, visual symptoms, and
      spectacle use. RESULTS: Sixty-five eyes (43 subjects) were included. After
      surgery, no significant differences between groups were observed in UDVA and MR
      values. UNVA at 33 cm was best in Group 3 (1 month: P = .032; 3 months: P =
      .031). Three months after surgery, UNVA was best in Group 1 at 50 cm (P = .017).
      No significant differences in internal aberration and contrast sensitivity were
      observed between groups and surgical satisfaction was worst in Group 3 (P =
      .001). A total of 87.0%, 85.7%, and 76.9% had spectacle independence in Groups 1,
      2, and 3, respectively (P = .080). CONCLUSIONS: TECNIS diffractive multifocal
      IOLs with lower add powers provide good vision over longer working distances and
      excellent distant vision. Subjects with lower add power had greater satisfaction,
      more spectacle independence, and fewer visual symptoms than those with +4.00 D
      add.

PMID- 26209233
TI  - 23 Gauge Vitrectomy, Endolaser, and Gas Tamponade Versus Vitrectomy Alone for
      Serous Macular Detachment Associated With Optic Disc Pit.
AB  - PURPOSE: To evaluate the clinical outcomes of 23 gauge vitrectomy, endolaser, and
      gas tamponade vs vitrectomy alone for the management of serous macular detachment
      associated with optic disc pits. DESIGN: Retrospective, comparative case series.
      METHODS: Seventeen eyes of 16 patients who underwent 23 gauge transconjunctival
      sutureless pars plana vitrectomy (PPV) for serous macular detachment associated
      with optic disc pits were evaluated in this study. Complete ophthalmologic
      examinations including optical coherence tomography (OCT) and fundus
      autofluorescence were evaluated at the baseline and during the postoperative
      follow-up period. Ten eyes of 9 cases that underwent 23 gauge PPV, endolaser, and
      gas tamponade were allocated to Group 1, and 7 eyes of 7 cases that underwent 23
      gauge PPV alone were allocated to Group 2. RESULTS: There were 6 male and 3
      female patients in Group 1, and the average age of patients was 24.7 years. There
      were 5 male and 2 female patients in Group 2 and the average age of patients was
      22.1 years. There was no difference in the postoperative visual acuity (P = .7)
      and postoperative central foveal thickness (P = .5) between the 2 groups. The
      mean time of the subretinal fluid resolution was significantly shorter in Group 1
      than in Group 2. OCT showed the inner layer separation improved before than
      serous retinal detachment. Preoperative features of the inner/outer segment
      junction correlate well with improvement of postoperative visual acuity.
      CONCLUSIONS: Vitrectomy alone without gas tamponade and laser photocoagulation is
      a safe and effective method for management of serous macular detachment resulting
      from optic disc pits as well as combined surgery.

PMID- 26209234
TI  - Pain-free treadmill exercise for patients with intermittent claudication: Are
      there gender differences?
AB  - Intermittent claudication, a common symptom of peripheral arterial disease,
      results in insufficient blood flow and oxygen supply to lower extremity muscles.
      Compared to men, women with peripheral arterial disease have a higher rate of
      mobility loss with peripheral arterial disease due to poorer lower extremity
      functioning. This study evaluates the effect of supervised pain-free treadmill
      exercise on improving performance in women with intermittent claudication due to
      peripheral arterial disease in comparison to men. A total of 26 participants
      (women, n = 9, 34.62%; mean age = 67.58 +/- 5.59 years; averaging 23.46 +/- 3.91
      visits and 10.46 +/- 0.99 weeks in the program) diagnosed with peripheral
      arterial disease, with symptoms of intermittent claudication, partook in a 45 min
      treadmill walk, twice per week, below the participant's minimal pain threshold.
      Female participants' change scores showed 752%, 278% and 115% improvement in mean
      walking distance, duration and rate, respectively. Men improved 334%, 149% and
      80%, respectively. Significant differences (p < 0.05) in pre and post
      measurements within each group support positive outcomes. No significant
      differences between groups were observed (Cohen's d effect size > 0.80). Our
      results suggest that women reap similar benefits from this low-intensity
      treadmill program in comparison to men. 

PMID- 26209236
TI  - Pharmacological In Vivo Inhibition of S-Nitrosoglutathione Reductase Attenuates
      Bleomycin-Induced Inflammation and Fibrosis.
AB  - Interstitial lung disease (ILD) characterized by pulmonary fibrosis and
      inflammation poses a substantial biomedical challenge due to often negative
      disease outcomes combined with the need to develop better, more effective
      therapies. We assessed the in vivo effect of administration of a pharmacological
      inhibitor of S-nitrosoglutathione reductase, SPL-334 (4-{[2-[(2-cyanobenzyl)thio]
      4-oxothieno[3,2-d]pyrimidin-3(4H)-yl]methyl}benzoic acid), in a mouse model of
      ILD induced by intratracheal instillation of bleomycin (BLM). Daily i.p.
      administration of SPL-334 alone at 0.3, 1.0, or 3.0 mg/kg had no effect on animal
      body weight, appearance, behavior, total and differential bronchoalveolar lavage
      (BAL) cell counts, or collagen accumulation in the lungs, showing no toxicity of
      our investigational compound. Similar administration of SPL-334 for 7 days before
      and for an additional 14 days after BLM instillation resulted in a preventive
      protective effect on the BLM challenge-induced decline in total body weight and
      changes in total and differential BAL cellularity. In the therapeutic treatment
      regimen, SPL-334 was administered at days 7-21 after BLM challenge. Such
      treatment attenuated the BLM challenge-induced decline in total body weight,
      changes in total and differential BAL cellularity, and magnitudes of histologic
      changes and collagen accumulation in the lungs. These changes were accompanied by
      an attenuation of BLM-induced elevations in pulmonary levels of profibrotic
      cytokines interleukin-6, monocyte chemoattractant protein-1, and transforming
      growth factor-beta (TGF-beta). Experiments in cell cultures of primary normal
      human lung fibroblast have demonstrated attenuation of TGF-beta-induced
      upregulation in collagen by SPL-334. It was concluded that SPL-334 is a potential
      therapeutic agent for ILD. 

PMID- 26209235
TI  - Uncovering metabolism in rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is a myogenic tumor classified as the most frequent soft
      tissue sarcoma affecting children and adolescents. The histopathological
      classification includes 5 different histotypes, with 2 most predominant referred
      as to embryonal and alveolar, the latter being characterized by adverse outcome.
      The current molecular classification identifies 2 major subsets, those harboring
      the fused Pax3-Foxo1 transcription factor generating from a recurrent specific
      translocation (fusion-positive RMS), and those lacking this signature but
      harboring mutations in the RAS/PI3K/AKT signaling axis (fusion-negative RMS).
      Since little attention has been devoted to RMS metabolism until now, in this
      review we summarize the "state of art" of metabolism and discuss how some of the
      molecular signatures found in this cancer, as observed in other more common
      tumors, can predict important metabolic challenges underlying continuous cell
      growth, oxidative stress resistance and metastasis, which could be the subject of
      future targeted therapies. 

PMID- 26209237
TI  - Effects of karanjin on cell cycle arrest and apoptosis in human A549, HepG2 and
      HL-60 cancer cells.
AB  - BACKGROUND: We have investigated the potential anticancer effects of karanjin, a
      principal furanoflavonol constituent of the Chinese medicine Fordia cauliflora,
      using cytotoxic assay, cell cycle arrest, and induction of apoptosis in three
      human cancer cell lines (A549, HepG2 and HL-60 cells). RESULTS: MTT cytotoxic
      assay showed that karanjin could inhibit the proliferation and viability of all
      three cancer cells. The induction of cell cycle arrest was observed via a PI
      (propidium iodide)/RNase Staining Buffer detection kit and analyzed by flow
      cytometry: karanjin could dose-dependently induce cell cycle arrest at G2/M phase
      in the three cell lines. Cell apoptosis was assessed by Annexin V-FITC/PI
      staining: all three cancer cells treated with karanjin exhibited significantly
      increased apoptotic rates, especially in the percentage of late apoptosis cells.
      CONCLUSION: Karanjin can induce cancer cell death through cell cycle arrest and
      enhance apoptosis. This compound may be effective clinically for cancer
      pharmacotherapy.

PMID- 26209238
TI  - Factors that lead to the use of crack cocaine in combination with marijuana in
      Brazil: a qualitative study.
AB  - BACKGROUND: In Brazil, crack cocaine use remains a healthcare challenge due to
      the rapid onset of its pleasurable effects, its ability to induce craving and
      addiction, and the fact that it is easily accessible. Delayed action on the part
      of the Brazilian Government in addressing the drug problem has led users to
      develop their own strategies for surviving the effects of crack cocaine use,
      particularly the drug craving and psychosis. In this context, users have sought
      the benefits of combining crack cocaine with marijuana. Our aim was to identify
      the reasons why users combine crack cocaine with marijuana and the health
      implications of doing so. METHODS: The present study is a qualitative study,
      using in-depth interviews and criteria-based sampling, following 27 crack cocaine
      users who combined its use with marijuana. Participants were recruited using the
      snowball sampling technique, and the point of theoretical saturation was used to
      define the sample size. Data were analyzed using the content analysis technique.
      RESULTS: The interviewees reported that the combination of crack cocaine use with
      marijuana provided "protection" (reduced undesirable effects, improved sleep and
      appetite, reduced craving for crack cocaine, and allowed the patients to recover
      some quality of life). CONCLUSIONS: Combined use of cannabis as a strategy to
      reduce the effects of crack exhibited several significant advantages,
      particularly an improved quality of life, which "protected" users from the
      violence typical of the crack culture. Crack use is considered a serious public
      health problem in Brazil, and there are few solution strategies. Within that
      limited context, the combination of cannabis and crack deserves more thorough
      clinical investigation to assess its potential use as a strategy to reduce the
      damage associated with crack use.

PMID- 26209239
TI  - Commentary on Bajada et al., (2015).

PMID- 26209240
TI  - A ferritin-like protein with antioxidant activity in Ureaplasma urealyticum.
AB  - BACKGROUND: Ureaplasma urealyticum is a major pathogen associated with many
      diseases. The ability of U. urealyticum to protect itself from oxidative stress
      is likely to be important for its pathogenesis and survival, but its oxidative
      stress tolerance mechanisms remain unclear. This study investigates the
      antioxidant activity of a ferritin-like protein from U. urealyticum. RESULTS: The
      uuferritin gene, which was up regulated when U. urealyticum was subjected to
      oxidative stress, was cloned from U. urealyticum and the corresponding
      recombinant protein uuferritin was purified. Uuferritin protein reduced the
      levels of hydroxyl radicals generated by the Fenton reaction as a consequence of
      its ferroxidase activity, and thus the protein protected DNA from oxidative
      damage. Furthermore, oxidation-sensitive Escherichia coli mutants transformed
      with pTrc99a-uuferritin showed significantly improved tolerance to oxidative
      stress compared to E. coli mutants transformed with an empty pTrc99a vector.
      CONCLUSIONS: The present work shows that uuferritin protein confers resistance to
      oxidative stress in vitro and in E. coli. The protective role of uuferritin
      provides a foundation for understanding the mechanisms of oxidative stress
      tolerance in U. urealyticum.

PMID- 26209241
TI  - Aspirin provocation increases 8-iso-PGE2 in exhaled breath condensate of aspirin
      hypersensitive asthmatics.
AB  - BACKGROUND: Isoprostanes are bioactive compounds formed by non-enzymatic
      oxidation of polyunsaturated fatty acids, mostly arachidonic, and markers of free
      radical generation during inflammation. In aspirin exacerbated respiratory
      disease (AERD), asthmatic symptoms are precipitated by ingestion of non-steroid
      anti-inflammatory drugs capable for pharmacologic inhibition of cyclooxygenase-1
      isoenzyme. We investigated whether aspirin-provoked bronchoconstriction is
      accompanied by changes of isoprostanes in exhaled breath condensate (EBC).
      METHODS: EBC was collected from 28 AERD subjects and 25 aspirin-tolerant
      asthmatics before and after inhalatory aspirin challenge. Concentrations of 8-iso
      PGF2alpha, 8-iso-PGE2, and prostaglandin E2 were measured using gas
      chromatography/mass spectrometry. Leukotriene E4 was measured by immunoassay in
      urine samples collected before and after the challenge. RESULTS: Before the
      challenge, exhaled 8-iso-PGF2alpha, 8-iso-PGE2, and PGE2 levels did not differ
      between the study groups. 8-iso-PGE2 level increased in AERD group only (p=0.014)
      as a result of the aspirin challenge. Urinary LTE4 was elevated in AERD, both in
      baseline and post-challenge samples. Post-challenge airways 8-iso-PGE2 correlated
      positively with urinary LTE4 level (p=0.046), whereas it correlated negatively
      with the provocative dose of aspirin (p=0.027). CONCLUSION: A significant
      increase of exhaled 8-iso-PGE2 after inhalatory challenge with aspirin was
      selective and not present for the other isoprostane measured. This is a novel
      finding in AERD, suggesting that inhibition of cyclooxygenase may elicit 8-iso
      PGE2 production in a specific mechanism, contributing to bronchoconstriction and
      systemic overproduction of cysteinyl leukotrienes.

PMID- 26209242
TI  - Effects of platelet-rich fibrin and piezosurgery on impacted mandibular third
      molar surgery outcomes.
AB  - INTRODUCTION: The aim of this study was the comparision of postoperative outcomes
      in impacted mandibular third molars that were treated using either platelet-rich
      fibrin (PRF), a combination of PRF and piezosurgery, or conventional rotatory
      osteotomy. PATIENT AND METHODS: The study included 20 patients; 40 extractions of
      impacted mandibular third molars were performed. Patients were divided into two
      main groups. In group A (n = 20), traditional surgery was performed on one side
      (Group 1, n = 10); traditional surgery was performed, and PRF was administered to
      the extracted socket on the other side of same patient (Group 2, n = 10). In
      group B (n = 20), on one side, piezosurgery was used for osteotomy, and PRF was
      administered (Group 3, n = 10); on the other side of same patient, traditional
      surgery was performed (Group 4, n = 10). Parameters assessed at baseline for each
      patient included pain, the number of analgesics taken, trismus, and cheek
      swelling. These variables were also assessed on postoperative days 1, 2, 3, and
      7. RESULTS: Statistical analysis revealed a significant reduction in
      postoperative pain (sum of 1(st), 2(nd), 3(rd) and 7(th) days) and trismus (on
      postoperative day 1) in group 2 (traditional surgery + PRF group), and in
      postoperative pain, the number of analgesics taken (sum of 1(st), 2(nd),3(rd) and
      7(th) days) and trismus (on postoperative day 1) in group 3 (piezosurgery + PRF
      group) compared to groups 1 and 4 (traditional surgery groups), (p <= 0.05).
      However, swelling on postoperative days 1, 3, and 7 did not differ among the
      groups (p > 0.05). Only difference was on second day between groups 1-4 and 2-4
      (p <= 0.05). CONCLUSIONS: The results of our study have shown that the use of PRF
      with traditional surgery and PRF combined with piezosurgery significantly reduced
      pain during the postoperative period. In addition, PRF in combination with
      piezosurgery significantly decreased the number of analgesics taken. Both
      operations also significantly decreased trismus 24 h after the surgery. As a
      result of this study, PRF and combination use of PRF and piezosurgery have
      positive effects in reducing postoperative outcomes after impacted third molar
      surgery.

PMID- 26209243
TI  - Anti-Mullerian hormone: a potentially useful biomarker for the diagnosis of
      canine Sertoli cell tumours.
AB  - BACKGROUND: Testicular tumours are common in dogs and in many cases do not give
      rise to clinical signs. In other cases, signs of feminization, hyperpigmentation
      or alopecia may be observed, most commonly associated with Sertoli cell tumours
      (SCT). Although these signs are often associated with elevated concentrations of
      oestradiol, analysis of oestradiol may give inconclusive results due to large
      variations among individuals. Other biomarkers are therefore needed. Anti
      Mullerian hormone (AMH) is expressed by the Sertoli cell. In humans, AMH has been
      shown to be a specific marker of Sertoli cell origin in gonadal tumours. Using
      immunohistochemistry, AMH has been shown to be a useful marker of immature and
      neoplastic Sertoli cells in dogs. The aim of the present study was to evaluate
      the clinical relevance of AMH analysis in peripheral blood in the diagnostic
      workup of dogs with suspected testicular tumours. RESULTS: Blood was collected
      from 20 dogs with a palpable testicular mass and from 27 healthy controls. Serum
      was analysed for oestradiol-17beta using a RIA and for AMH using an ELISA. The
      Mann-Whitney U test was used to compare hormone concentrations between different
      groups. All control dogs had AMH concentrations <= 10 ng/mL, except one outlier
      that had a concentration of 43 ng/mL. Six dogs with SCT or mixed tumours
      containing SCT had AMH concentrations higher than 22 ng/mL, significantly higher
      than AMH concentrations in control dogs (P = 0.0004). Concentrations between 10
      and 22 ng/mL were found in about half of the dogs with non-neoplastic testicular
      pathologies or with testicular tumours other than SCTs. Age did not significantly
      affect concentrations of AMH in the control dogs. CONCLUSION: AMH was shown to be
      a promising biomarker for the diagnosis of Sertoli cell tumours in dogs.

PMID- 26209244
TI  - Comparison of carotid plaque tissue characteristics in patients with acute
      coronary syndrome or stable angina pectoris: assessment by iPlaque,
      transcutaneous carotid ultrasonography with integrated backscatter analysis.
AB  - BACKGROUND: The association of the tissue characteristics of carotid plaques with
      coronary artery disease has attracted interest. The present study compared the
      tissue characteristics of carotid plaques in patients with acute coronary
      syndrome (ACS) with those in patients with stable angina pectoris (SAP) using the
      iPlaque system, which is based on ultrasound integrated backscatter. METHODS AND
      RESULTS: Carotid ultrasound examinations were performed in 26 patients with ACS,
      and 38 age- and gender-matched patients with SAP. Neither plaque area nor maximal
      intima-media thickness differed significantly between the two groups. However,
      the average integrated backscatter value within the plaque was greater in the ACS
      patients than in the SAP patients. iPlaque analysis revealed that the percentage
      blue area (lipid pool) was greater in the ACS patients than in the SAP patients
      (43.4 +/- 11.2 vs 18.3 +/- 10.3%, p < 0.0001), and that the percentage green area
      (fibrosis) was lower in the ACS than in the SAP patients (7.5 +/- 7.5% vs 20.7 +/
      11.7%, p < 0.0001). CONCLUSIONS: The lipid component of carotid plaques is
      greater in ACS patients than in SAP patients. Our iPlaque system provides a
      useful and feasible method for the tissue characterization of carotid plaques in
      the clinical setting.

PMID- 26209245
TI  - Beyond 2/3 and 1/3: The Complex Signatures of Sex-Biased Admixture on the X
      Chromosome.
AB  - Sex-biased demography, in which parameters governing migration and population
      size differ between females and males, has been studied through comparisons of X
      chromosomes, which are inherited sex-specifically, and autosomes, which are not.
      A common form of sex bias in humans is sex-biased admixture, in which at least
      one of the source populations differs in its proportions of females and males
      contributing to an admixed population. Studies of sex-biased admixture often
      examine the mean ancestry for markers on the X chromosome in relation to the
      autosomes. A simple framework noting that in a population with equally many
      females and males, two-thirds of X chromosomes appear in females, suggests that
      the mean X-chromosomal admixture fraction is a linear combination of female and
      male admixture parameters, with coefficients 2/3 and 1/3, respectively. Extending
      a mechanistic admixture model to accommodate the X chromosome, we demonstrate
      that this prediction is not generally true in admixture models, although it holds
      in the limit for an admixture process occurring as a single event. For a model
      with constant ongoing admixture, we determine the mean X-chromosomal admixture,
      comparing admixture on female and male X chromosomes to corresponding autosomal
      values. Surprisingly, in reanalyzing African-American genetic data to estimate
      sex-specific contributions from African and European sources, we find that the
      range of contributions compatible with the excess African ancestry on the X
      chromosome compared to autosomes has a wide spread, permitting scenarios either
      without male-biased contributions from Europe or without female-biased
      contributions from Africa. 

PMID- 26209247
TI  - Latent Structure of the Behavior Rating Inventory of Executive Function-Adult
      Version (BRIEF-A) After Mild Traumatic Brain Injury.
AB  - One hundred persons with mild traumatic brain injury (TBI) and their informants
      completed the Behavior Rating Inventory of Executive Function-Adult Version
      (BRIEF-A) within 1-12 months after injury. Exploratory maximum-likelihood factor
      analysis with oblique rotation revealed that although a traditional 2-factor
      model fit the informant-report data well, a 3-factor solution fit the self-report
      data relatively best. These factors were labeled Metacognition, Behavioral
      Regulation, and Emotional Regulation. The presence of a premorbid history of
      outpatient psychiatric treatment was strongly predictive of higher scores
      (reflecting more perceived problems) on each of these 3 factors. Lower
      educational attainment was associated with higher scores on the Behavioral
      Regulation factor, whereas absence of intracranial findings on neuroimaging was
      associated with higher scores on the Emotional Regulation factor. It is concluded
      that, after mild TBI, self-report data on the BRIEF-A can be interpreted along a
      3-factorial model and that high elevations on this instrument are strongly
      affected by premorbid complications. 

PMID- 26209248
TI  - Potentiality of a ceramic membrane reactor for the laccase-catalyzed removal of
      bisphenol A from secondary effluents.
AB  - In this study, the removal of bisphenol A (BPA) by laccase in a continuous
      enzymatic membrane reactor (EMR) was investigated. The effects of key parameters,
      namely, type of laccase, pH, and enzyme activity, were initially evaluated. Once
      optimal conditions were determined, the continuous removal of the pollutant in an
      EMR was assessed in synthetic and real biologically treated wastewaters. The
      reactor configuration consisted of a stirred tank reactor coupled to a ceramic
      membrane, which prevented the sorption of the pollutant and allowed the recovery
      and recycling of laccase. Nearly complete removal of BPA was attained under both
      operation regimes with removal yields above 94.5 %. In experiments with real
      wastewater, the removal of BPA remained high while the presence of colloids and
      certain ions and the formation of precipitates on the membrane potentially
      affected enzyme stability and made necessary the periodic addition of laccase.
      Polymerization and degradation were observed as probable mechanisms of BPA
      transformation by laccase.

PMID- 26209249
TI  - Poor Anticoagulation Control in Atrial Fibrillation: How Much Longer?

PMID- 26209246
TI  - Mitochondrial metabolism in hematopoietic stem cells requires functional FOXO3.
AB  - Hematopoietic stem cells (HSC) are primarily dormant but have the potential to
      become highly active on demand to reconstitute blood. This requires a swift
      metabolic switch from glycolysis to mitochondrial oxidative phosphorylation.
      Maintenance of low levels of reactive oxygen species (ROS), a by-product of
      mitochondrial metabolism, is also necessary for sustaining HSC dormancy. Little
      is known about mechanisms that integrate energy metabolism with hematopoietic
      stem cell homeostasis. Here, we identify the transcription factor FOXO3 as a new
      regulator of metabolic adaptation of HSC. ROS are elevated in Foxo3(-/-) HSC that
      are defective in their activity. We show that Foxo3(-/-) HSC are impaired in
      mitochondrial metabolism independent of ROS levels. These defects are associated
      with altered expression of mitochondrial/metabolic genes in Foxo3(-/-)
      hematopoietic stem and progenitor cells (HSPC). We further show that defects of
      Foxo3(-/-) HSC long-term repopulation activity are independent of ROS or mTOR
      signaling. Our results point to FOXO3 as a potential node that couples
      mitochondrial metabolism with HSC homeostasis. These findings have critical
      implications for mechanisms that promote malignant transformation and aging of
      blood stem and progenitor cells. 

PMID- 26209250
TI  - Netrin-1 as a novel therapeutic target in cardiovascular disease: to activate or
      inhibit?
AB  - Netrins are a family of laminin-like proteins, which were initially identified
      for their role in embryonic axonal guidance. Over recent years, it has become
      apparent that netrin-1 may additionally be involved in the underlying pathology
      of several multisystem diseases, making it an attractive potential therapeutic
      target. It is involved in postnatal angiogenesis, particularly in the context of
      an ischaemic insult, although there are conflicting reports as to whether netrin
      1 acts in a pro- or anti-angiogenic capacity. In atherosclerosis, opposing
      effects have similarly been reported on plaque progression, due to the ability of
      netrin-1 to inhibit both macrophage egress from and monocyte ingress into
      lesions. Netrin-1 has also been shown to exert a cardioprotective action in the
      context of ischaemia-reperfusion injury following myocardial infarction.
      Moreover, urinary netrin-1 levels rise in response to acute kidney injury and at
      a faster rate than traditional markers of renal impairment, highlighting a
      potential clinical role for netrin-1 as a biomarker of renal function. The
      increased urinary excretion of netrin-1 during kidney disease is paralleled by a
      down-regulation of its plasma levels, with potential implications at a systemic
      level. In summary, the role of netrin-1 in cardiovascular disease is an emerging
      area of research requiring further in-depth study to elucidate its mechanism of
      action and potential as a therapeutic target, especially in view of its seemingly
      contradictory actions in certain physiological pathways which serve to highlight
      its manifold and often opposite effects in numerous physiological and
      pathophysiological processes. 

PMID- 26209251
TI  - Transmural APD gradient synchronizes repolarization in the human left ventricular
      wall.
AB  - AIMS: The duration and morphology of the T wave predict risk for ventricular
      fibrillation. A transmural gradient in action potential duration (APD) in the
      ventricular wall has been suggested to underlie the T wave in humans. We
      hypothesize that the transmural gradient in APD compensates for the normal
      endocardium-to-epicardium activation sequence and synchronizes repolarization in
      the human ventricular wall. METHODS AND RESULTS: We made left ventricular wedge
      preparations from 10 human donor hearts and measured transmural activation and
      repolarization patterns by optical mapping, while simultaneously recording a
      pseudo-ECG. We also studied the relation between local timings of repolarization
      with the T wave in silico. During endocardial pacing (1 Hz), APD was longer at
      the subendocardium than at the subepicardium (360 +/- 17 vs. 317 +/- 20 ms, P <
      0.05). The transmural activation time was 32 +/- 4 ms and resulted in final
      repolarization of the subepicardium at 349 +/- 18 ms. The overall transmural
      dispersion in repolarization time was smaller than that of APD. During epicardial
      pacing, the dispersion in repolarization time increased, whereas that of APD
      remained similar. The morphology of the T wave did not differ between endocardial
      and epicardial stimulation. Simulations explained the constant T wave morphology
      without transmural APD gradients. CONCLUSION: The intrinsic transmural difference
      in APD compensates for the normal cardiac activation sequence, resulting in more
      homogeneous repolarization of the left ventricular wall. Our data suggest that
      the transmural repolarization differences do not fully explain the genesis of the
      T wave.

PMID- 26209252
TI  - Cardiac mechano-electric coupling: a role in regulating normal function of the
      heart?

PMID- 26209253
TI  - [Choroid plexus tumours in childhood: Experience in Sant Joan de Deu hospital].
AB  - Choroid plexus tumours are rare, with a peak incidence in the first two years of
      life. The most common location is the lateral ventricle in children, while in
      adults it is the fourth ventricle. The most common clinical manifestation is the
      signs and symptoms of intracranial hypertension. They are histologically
      classified as plexus papilloma, atypical plexus papilloma, and plexus carcinoma.
      A review is presented on choroid plexus tumours treated in the Hospital Sant Joan
      de Deu between 1980 and 2014. A total of 18 patients have been treated. An
      analysis was made of the demographic, clinical, histological data, treatment, and
      recurrences. The treatment of choice is complete resection, accompanied by
      adjuvant therapy in carcinomas. In atypical papillomas, the use of adjuvant
      therapies is controversial, reserving radiation therapy for recurrences.
      Papillomas have a good outcome, whereas atypical papillomas and carcinomas
      outcome is poor. 

PMID- 26209254
TI  - Aromatase overexpression in dysfunctional adipose tissue links obesity to
      postmenopausal breast cancer.
AB  - The number of breast cancer cases has increased in the last a few decades and
      this is believed to be associated with the increased prevalence of obesity
      worldwide. The risk of breast cancer increases with age beyond menopause and the
      relationship between obesity and the risk of breast cancer in postmenopausal
      women is well established. The majority of postmenopausal breast cancers are
      estrogen receptor (ER) positive and estrogens produced in the adipose tissue
      promotes tumor formation. Obesity results in the secretion of inflammatory
      factors that stimulate the expression of the aromatase enzyme, which converts
      androgens into estrogens in the adipose tissue. Evidence demonstrating a link
      between obesity and breast cancer has led to the investigation of metabolic
      pathways as novel regulators of estrogen production, including pathways that can
      be targeted to inhibit aromatase specifically within the breast. This review aims
      to present some of the key findings in this regard. 

PMID- 26209255
TI  - Feasibility and results of pull-percutaneous endoscopic gastrostomy for enteral
      nutrition in adults with severe cerebral palsy.
AB  - BACKGROUND & AIMS: Eating and swallowing impairments often get worse as patients
      with severe cerebral palsy (CP) get older, creating increased demand for
      percutaneous endoscopic gastrostomy (PEG) tube placement. Here we investigated
      the feasibility, safety, adverse events (AEs) and outcomes of PEG in adult CP.
      METHODS: We performed a retrospective study of 26 consecutive severe adult (age:
      28 [19-48] yrs) CP patients who underwent pull-PEG tube placement under general
      anesthesia between 2005 and 2012 (median follow-up: 23 [6-64] months) at the same
      tertiary hospital centre. RESULTS: The procedure was a technical success for 19
      patients (BMI: 13.8 [10.7-21.4]) with (n = 11) or without (n = 8) previous
      respiratory disorder. Indications were mainly swallowing disorders (n = 14) and
      inadequate oral intake (n = 8). Early AEs were 7 transient oxygen needs, 3 local
      wound infections and 2 transient ileus. Long-term AEs were 9 non-severe
      gastrostomy incidents. There was no significant improvement in neurological
      status but respiratory function was improved in 6 patients and enteral nutrition
      enabled a significant median weight gain of 4.2 [1-8.8] kg (P < 0.01). Quality-of
      life assessed by relatives and the healthcare team was improved in 13/16 and
      13/15 cases respectively. AEs and outcomes did not differ significantly with
      previous respiratory disorder or nutritional status. CONCLUSIONS: PEG tube
      placement is feasible in adult CP, although the risk of failure is increased by
      anatomical specificities. Previous respiratory disorders and undernourishment did
      not increase AE rates or modify outcomes. There were positive changes over time
      for nutritional status and perceived quality-of-life, but no neurological
      improvement.

PMID- 26209256
TI  - Effects of beta-carotene fortified synbiotic food on metabolic control of
      patients with type 2 diabetes mellitus: A double-blind randomized cross-over
      controlled clinical trial.
AB  - BACKGROUND & AIMS: The aim of the present study was to determine the beneficial
      effects of beta-carotene fortified synbiotic food intake on metabolic status in
      patients with type 2 diabetes mellitus (T2DM). METHODS: This randomized double
      blinded placebo-controlled crossover clinical trial was conducted among 51
      patients with T2DM. Individuals were randomly assigned to take either a beta
      carotene fortified synbiotic (n = 51) or control food (n = 51) for 6 weeks. The
      beta-carotene fortified synbiotic was containing Lactobacillus sporogenes (1 *
      10(7) CFU), 0.1 g inulin and 0.05 g beta-carotene. Control food (the same
      substance without probiotic, inulin and beta-carotene) was packed in identical 9
      g packages. Patients were requested to use the beta-carotene fortified synbiotic
      and control foods three times a day. RESULTS: Beta-carotene fortified synbiotic
      food consumption resulted in a significant decrease in insulin (-1.00 +/- 7.90
      vs. +3.68 +/- 6.91 MUIU/mL, P = 0.002), HOMA-IR (-0.73 +/- 3.96 vs. +1.82 +/-
      vbnm4.09, P = 0.002), HOMA-B (-0.52 +/- 19.75 vs. +8.71 +/- 17.15, P = 0.01),
      triglycerides (-2.86 +/- 49.53 vs. +20.14 +/- 50.10 mg/dL, P = 0.02), VLDL
      cholesterol levels (-0.57 +/- 9.90 vs. +4.03 +/- 10.02 mg/dL, P = 0.02) and total
      /HDL-cholesterol ratio (-0.01 +/- 1.08 vs. +0.64 +/- 0.81, P = 0.001) compared to
      the control food. In addition, beta-carotene fortified synbiotic food consumption
      led to elevated plasma nitric oxide (NO) (+6.83 +/- 16.14 vs. -3.76 +/- 16.47
      MUmol/L, P = 0.001) and glutathione (GSH) (+36.58 +/- 296.71 vs. -92.04 +/-
      243.05 MUmol/L, P = 0.01). CONCLUSIONS: Beta-carotene fortified synbiotic food
      intake in patients with T2DM for 6 weeks had favorable effects on insulin, HOMA
      IR, HOMA-B, triglycerides, VLDL-cholesterol, total-/HDL-cholesterol ratio, NO and
      GSH levels.

PMID- 26209257
TI  - Involvement of p38 MAPK activation mediated through AT1 receptors on spinal
      astrocytes and neurons in angiotensin II- and III-induced nociceptive behavior in
      mice.
AB  - We have previously demonstrated the possibility that angiotensin (Ang) II and its
      N-terminal metabolite Ang (1-7) act as neurotransmitters and/or neuromodulators
      in the spinal transmission of nociceptive information. Ang III, which is a C
      terminal metabolite of Ang II, can also act on AT1 receptors, but its role in
      spinal nociceptive transmission remains unclear. Therefore, we examined the role
      of Ang III on the spinal nociceptive system in comparison with that of Ang II.
      Intrathecal (i.t.) administration of Ang III into mice produced a nociceptive
      behavior, which was dose-dependently inhibited by the co-administration of the
      AT1 receptor antagonist losartan and the p38 MAPK inhibitor SB203580, but not by
      the AT2 receptor antagonist PD123319, MEK1/2 inhibitor U0126 and JNK inhibitor
      SP600125. In addition, Ang III increased the phosphorylation of p38 MAPK in the
      dorsal lumbar spinal cord, which was inhibited by losartan. These effects were
      similar to those of observed with Ang II. The nociceptive behavior produced by
      Ang II or III was also attenuated by the administration of the astrocytic
      inhibitor L-alpha-aminoadipic acid, but not by the microglial inhibitor
      minocycline. Double immunohistochemical staining showed that spinal AT1 receptors
      were expressed on neurons and astrocytes, and that i.t. administration of either
      Ang II or III phosphorylated p38 MAPK in both spinal astrocytes and neurons.
      These results indicate that Ang III produces nociceptive behavior similar to Ang
      II, and suggest that the phosphorylation of p38 MAPK mediated through AT1
      receptors on spinal astrocytes and neurons contributes to Ang II- and III-induced
      nociceptive behavior.

PMID- 26209258
TI  - Coordination between Drosophila Arc1 and a specific population of brain neurons
      regulates organismal fat.
AB  - The brain plays a critical yet incompletely understood role in regulating
      organismal fat. We performed a neuronal silencing screen in Drosophila larvae to
      identify brain regions required to maintain proper levels of organismal fat. When
      used to modulate synaptic activity in specific brain regions, the enhancer-trap
      driver line E347 elevated fat upon neuronal silencing, and decreased fat upon
      neuronal activation. Unbiased sequencing revealed that Arc1 mRNA levels increase
      upon E347 activation. We had previously identified Arc1 mutations in a high-fat
      screen. Here we reveal metabolic changes in Arc1 mutants consistent with a high
      fat phenotype and an overall shift toward energy storage. We find that Arc1
      expressing cells neighbor E347 neurons, and manipulating E347 synaptic activity
      alters Arc1 expression patterns. Elevating Arc1 expression in these cells
      decreased fat, a phenocopy of E347 activation. Finally, loss of Arc1 prevented
      the lean phenotype caused by E347 activation, suggesting that Arc1 activity is
      required for E347 control of body fat. Importantly, neither E347 nor Arc1
      manipulation altered energy-related behaviors. Our results support a model
      wherein E347 neurons induce Arc1 in specific neighboring cells to prevent excess
      fat accumulation. 

PMID- 26209259
TI  - Auditory nerve disease and auditory neuropathy spectrum disorders.
AB  - In 1996, a new type of bilateral hearing disorder was discerned and published
      almost simultaneously by Kaga et al. [1] and Starr et al. [2]. Although the
      pathophysiology of this disorder as reported by each author was essentially
      identical, Kaga used the term "auditory nerve disease" and Starr used the term
      "auditory neuropathy". Auditory neuropathy (AN) in adults is an acquired disorder
      characterized by mild-to-moderate pure-tone hearing loss, poor speech
      discrimination, and absence of the auditory brainstem response (ABR) all in the
      presence of normal cochlear outer hair cell function as indicated by normal
      distortion product otoacoustic emissions (DPOAEs) and evoked summating potentials
      (SPs) by electrocochleography (ECoG). A variety of processes and etiologies are
      thought to be involved in its pathophysiology including mutations of the OTOF
      and/or OPA1 genes. Most of the subsequent reports in the literature discuss the
      various auditory profiles of patients with AN [3,4] and in this report we present
      the profiles of an additional 17 cases of adult AN. Cochlear implants are useful
      for the reacquisition of hearing in adult AN although hearing aids are
      ineffective. In 2008, the new term of Auditory Neuropathy Spectrum Disorders
      (ANSD) was proposed by the Colorado Children's Hospital group following a
      comprehensive study of newborn hearing test results. When ABRs were absent and
      DPOAEs were present in particular cases during newborn screening they were
      classified as ANSD. In 2013, our group in the Tokyo Medical Center classified
      ANSD into three types by following changes in ABRs and DPOAEs over time with
      development. In Type I, there is normalization of hearing over time, Type II
      shows a change into profound hearing loss and Type III is true auditory
      neuropathy (AN). We emphasize that, in adults, ANSD is not the same as AN. 

PMID- 26209260
TI  - Association of serum 25-hydroxyvitamin D with serum IgE levels in Korean adults.
AB  - OBJECTIVE: Studies about the association between vitamin D and allergic disease
      and the immune-modulatory function of vitamin D have increased in the recent
      years. However, not enough studies have been conducted for concrete conclusion
      about the association vitamin D and allergy. We investigate the association
      between serum immunoglobulin E (IgE) and serum 25-hydroxyvitamin D (25(OH)D)
      levels in Korean adults. METHODS: We used data of 1969 subjects from the 2010
      Korean National Health and Nutrition Examination Survey. Total IgE,
      Dermatophagoides farinae (Df)-specific IgE, and serum 25(OH)D levels were
      analyzed. Other variables included sex, age, body mass index, smoking history,
      and economic status. Adjusted regression analysis was used to examine the
      independent association of 25(OH)D with serum IgE levels. RESULTS: When we
      divided all subjects into four groups according to the serum 25(OH)D level: Q1
      (lowest), Q2, Q3, and Q4 (highest), the median TIgE level increased with higher
      quartiles in the Kruskal-Wallis test (p<0.001). Also, the prevalence of Df
      sensitization was highest in Q4. Serum vitamin D was positively associated with
      logarithmic transformed total IgE with base of 10 (LogTIgE) (coefficient (B),
      0.011; 95% confidence interval, 0.001-0.021). Furthermore, a positive association
      between 25(OH)D and LogTIgE was found only in men with Df sensitization, but not
      in men without Df sensitization and women with/without Df sensitization. However,
      the mean serum 25(OH)D level was significantly lower in participants who were
      clinically diagnosed with asthma or atopic dermatitis than participants without a
      history of asthma or atopic dermatitis, respectively. CONCLUSION: Serum 25(OH)D
      levels were positively associated with total IgE levels. Furthermore, the
      association between serum 25(OH)D and total IgE levels could vary depending on
      sex or allergic sensitization. But, the mean serum 25(OH)D level was lower in
      participants with asthma or atopic dermatitis history than participants without
      history of asthma or atopic dermatitis. Prospective further studies will be
      required to verify this discrepancy.

PMID- 26209261
TI  - Temperature-Triggered Protein Adsorption on Polymer-Coated Nanoparticles in
      Serum.
AB  - The protein corona, which forms on the nanoparticle's surface in most biological
      media, determines the nanoparticle's physicochemical characteristics. The
      formation of the protein corona has a significant impact on the biodistribution
      and clearance of nanoparticles in vivo. Therefore, the ability to influence the
      formation of the protein corona is essential to most biomedical applications,
      including drug delivery and imaging. In this study, we investigate the protein
      adsorption on nanoparticles with a hydrodynamic radius of 30 nm and a coating of
      thermoresponsive poly(2-isopropyl-2-oxazoline) in serum. Using multiangle dynamic
      light scattering (DLS) we demonstrate that heating of the nanoparticles above
      their phase separation temperature induces the formation of agglomerates, with a
      hydrodynamic radius of 1 MUm. In serum, noticeably stronger agglomeration occurs
      at lower temperatures compared to serum-free conditions. Cryogenic transmission
      electron microscopy (cryo-TEM) revealed a high packing density of agglomerates
      when serum was not present. In contrast, in the presence of serum, agglomerated
      nanoparticles were loosely packed, indicating that proteins are intercalated
      between them. Moreover, an increase in protein content is observed upon heating,
      confirming that protein adsorption is induced by the alteration of the surface
      during phase separation. After cooling and switching the surface back, most of
      the agglomerates were dissolved and the main fraction returned to the original
      size of approximately 30 nm as shown by asymmetrical flow-field flow
      fractionation (AF-FFF) and DLS. Furthermore, the amounts of adsorbed proteins are
      similar before and after heating the nanoparticles to above their phase
      separation temperature. Overall, our results demonstrate that the
      thermoresponsivity of the polymer coating enables turning the corona formation on
      nanoparticles on and off in situ. As the local heating of body areas can be
      easily done in vivo, the thermoresponsive coating could potentially be used to
      induce the agglomeration of nanoparticles and proteins and the accumulation of
      nanoparticles in a targeted body region. 

PMID- 26209262
TI  - Phytochemical analysis with the antioxidant and aldose reductase inhibitory
      capacities of Tephrosia humilis aerial parts' extracts.
AB  - The aerial parts of Tephrosia humilis were tested about their antioxidant
      potential, their ability to inhibit the aldose/aldehyde reductase enzymes and
      their phenolic content. The plant material was exhaustively extracted with
      petroleum ether, dichloromethane and methanol, consecutively. The concentrated
      methanol extract was re-extracted, successively, with diethyl ether, ethyl
      acetate and n-butanol. All extracts showed significant antioxidant capacity, but
      the most effective was the ethyl acetate extract. As about the aldose reductase
      inhibition, all fractions, except the aqueous, were strong inhibitors of the
      enzyme, with the n-butanolic and ethyl acetate fractions to inhibit the enzyme
      above 75%. These findings provide support to the ethnopharmacological usage of
      the plant as antioxidant and validate its potential to act against the long-term
      diabetic complications. The phytochemical analysis showed the presence of 1,4
      dihydroxy-3,4-(epoxyethano)-5-cyclohexene(1), cleroindicin E(2), lupeol(3),
      methyl p-coumarate(4), methyl 4-hydroxybenzoate(5), prunin(6), 5,7,2',5'
      tetrahydroxyflavanone 7-rutinoside(7), protocatechuic acid(8), luteolin 7
      glucoside(9), apigenin(10), naringin(11), rhoifolin(12) and luteolin 7
      glucuronate(13). 

PMID- 26209263
TI  - Increased Tpeak-Tend interval is highly and independently related to arrhythmic
      events in Brugada syndrome.
AB  - BACKGROUND: Risk stratification in Brugada syndrome (BS) remains controversial.
      The time interval between the peak and the end of the T wave (Tpe interval), a
      marker of transmural dispersion of repolarization, has been linked to malignant
      ventricular arrhythmias in various settings but leads to discordant results in
      BS. OBJECTIVE: We study the correlation of the Tpe interval with arrhythmic
      events in a large cohort of patients with BS. METHODS: A total of 325 consecutive
      patients with BS (mean age 47+/-13 years, 259 men-80%) with spontaneous (n=143,
      44%) or drug-induced (n=182, 56%) type 1 electrocardiogram were retrospectively
      included. 235 were asymptomatic (70%), 80 presented with unexplained syncope
      (22%), and 10 presented with sudden death (SD) or appropriate implantable
      cardioverter-defibrillator therapy (AT) (8%) at diagnosis or over a mean follow
      up of 48 +/- 34 months. The Tpe interval was calculated as the difference between
      the QT interval and the QT peak interval as measured in each of the precordial
      leads. RESULTS: The Tpe interval from lead V1 to lead V4, maximum value of the
      Tpe interval (max Tpe), and Tpe dispersion in all precordial leads were
      significantly higher in patients with SD/AT or in patients with syncope than in
      asymptomatic patients (P < .001). A max Tpe of >=100 ms was present in 47 of 226
      asymptomatic patients (21%), in 48 of 73 patients with syncope (66%), and in 22
      of 26 patients with SD/AT (85%) (P < .0001). In multivariate analysis, a max Tpe
      of >=100 ms was independently related to arrhythmic events (odds ratio 9.61; 95%
      confidence interval 3.13-29.41; P < .0001). CONCLUSION: The Tpe interval in the
      precordial leads is highly related to malignant ventricular arrhythmias in this
      large cohort of patients with BS. This simple electrocardiographic parameter
      could be used to refine risk stratification.

PMID- 26209264
TI  - CRISPR-Cas: New Tools for Genetic Manipulations from Bacterial Immunity Systems.
AB  - Prokaryotic CRISPR-Cas loci encode proteins that function as an adaptive immune
      system against infectious viruses and plasmids. Immunity is mediated by Cas
      nucleases and small RNA guides, which specify a cleavage site within the genome
      of the invader. In type II CRISPR-Cas systems, the RNA-guided Cas9 nuclease
      cleaves the DNA. Cas9 can be reprogrammed to create double-strand DNA breaks in
      the genomes of a variety of organisms, from bacteria to human cells. Repair of
      Cas9 lesions by homologous recombination or nonhomologous end joining mechanisms
      can lead to the introduction of specific nucleotide substitutions or indel
      mutations, respectively. Furthermore, a nuclease-null Cas9 has been developed to
      regulate endogenous gene expression and to label genomic loci in living cells.
      Targeted genome editing and gene regulation mediated by Cas9 are easy to program,
      scale, and multiplex, allowing researchers to decipher the causal link between
      genetic and phenotypic variation. In this review, we describe the most notable
      applications of Cas9 in basic biology, translational medicine, synthetic biology,
      biotechnology, and other fields. 

PMID- 26209265
TI  - Synthesis and optical properties of chlorin monomer, dimer and trimer on an amino
      nitrogen atom.
AB  - Naturally occurring chlorophyll-a was chemically modified to methyl 3-aminomethyl
      pyropheophorbides-a including primary, secondary, and tertiary amines. Reductive
      amination of methyl pyropheophorbide-d possessing the 3-formyl group with ammonia
      efficiently gave a chlorin dimer covalently linked with CH2NHCH2 at the 3
      position, which was transformed into a trimer through the substitution at the
      amino group. Conformational analyses by (1)H NMR spectroscopic observation and
      molecular modeling estimation indicated that the dimer and trimer were apt to
      form closely packed structures. Chlorin chromophores in the dimer and trimer were
      weakly interacted in dichloromethane to shift their Qy absorption bands to longer
      wavelengths by 4-6nm than the maxima of the corresponding monomer. In the red
      shifted Qy region, the trimer gave an S-shaped circular dichroism band by exciton
      coupling of composite chlorin units. All the semi-synthetic chlorophyll
      derivatives were highly fluorescent and no intramolecular quenching was observed
      even in the trimer. The behaviors would be ascribable to the formation of compact
      conformers and suppression of intramolecular motion, which are important to
      construct light-harvesting antenna complexes in phototrophs and their model
      systems. 

PMID- 26209266
TI  - Synthesis and antifungal evaluation of head-to-head and head-to-tail bisamidine
      compounds.
AB  - Herein, we describe the antifungal evaluation of 43 bisamidine compounds, of
      which 26 are new, having the scaffold [Am]-[HetAr]-[linker]-[HetAr]-[Am], in
      which [Am] is a cyclic or acyclic amidine group, [linker] is a benzene, pyridine,
      pyrimidine, pyrazine ring, or an aliphatic chain of two to four carbon, and
      [HetAr] is a 5,6-bicyclic heterocycle such as indole, benzimidazole,
      imidazopyridine, benzofuran, or benzothiophene. In the head-to-head series the
      two [HetAr] units are oriented such that the 5-membered rings are connected
      through the linker, and in the head-to-tail series, one of the [HetAr] systems is
      connected through the 6-membered ring; additionally, in some of the head-to-tail
      compounds, the [linker] is omitted. Many of these compounds exhibited significant
      antifungal activity against Candida albicans, Candida krusei, Candida glabrata,
      Candida parapsilosis, and Cryptococcus neoformans (MIC ? 4 MUg/ml). The most
      potent compounds, for example, P10, P19 and P34, are comparable in antifungal
      activities to amphotericin B (MIC 0.125 MUg/ml). They exhibited rapid fungicidal
      activity (>3 log10 decrease in cfu/ml in 4h) at concentrations equivalent to 4*
      the MIC in time kill experiments. The bisamidines strongly inhibited DNA, RNA and
      cell wall biosynthesis in C. albicans in macromolecular synthesis assays.
      However, the half-maximal inhibitory concentration for DNA synthesis was
      approximately 30-fold lower than those for RNA and cell wall biosynthesis.
      Fluorescence microscopy of intact cells of C. albicans treated with a bisamidine
      exhibited enhanced fluorescence in the presence of DNA, demonstrating that the
      bisamidine was localized to the nucleus. The results of this study show that
      bisamidines are potent antifungal agents with rapid fungicidal activity, which is
      likely to be the result of their DNA-binding activity. Although it was difficult
      to obtain a broad-spectrum antifungal compound with low cytotoxicity, some of the
      compounds (e.g., P9, P14 and P43) exhibited favorable CC50 values against HeLa
      cells and maintained considerable antifungal activity.

PMID- 26209267
TI  - Role of polyol moiety of amphotericin B in ion channel formation and sterol
      selectivity in bilayer membrane.
AB  - Amphotericin B (AmB) is a polyene macrolide antibiotic widely used to treat
      mycotic infections. In this paper, we focus on the role of the polyol moiety of
      AmB in sterol selectivity using 7-oxo-AmB, 7alpha-OH-AmB, and 7beta-OH-AmB. The 7
      OH analogs were prepared from 7-oxo-AmB. Their K(+) flux activity in liposomes
      showed that introduction of an additional ketone or hydroxy group on the polyol
      moiety reduces the original activity. Conformational analyses of these
      derivatives indicated that intramolecular hydrogen-bonding network possibly
      influenced the conformational rigidity of the macrolactone ring, and stabilized
      the active conformation in the membrane. Additionally, the flexible polyol leads
      to destabilization of the whole macrolactone ring conformation, resulting in a
      loss of sterol selectivity. 

PMID- 26209268
TI  - Operation and performance evaluation of high-speed filter using porous non-woven
      filamentous fibre for the treatment of turbid water.
AB  - This study was carried out to identify the filter performance of fibre filter
      module treating high-turbidity water at extremely high filtration rates (1000
      2500 m/day). The effects of filter aid chemical (polyaluminium chloride (PAC)),
      filtration rate and particles size on filter performance were investigated. It
      was found that PAC was a crucial factor influencing the separation process. Even
      though the optimum PAC dose for the raw water with turbidity of 50 nephelometric
      turbidity units (NTU) was 0.5 mg/L, the turbidity removal efficiencies were
      similar as the raw water turbidity was no more than 50 NTU. As expected, the
      filter performance was negatively affected by the increased filtration rate.
      However, the turbidity removal efficiency at an extremely high filtration rate
      still was amazing and attractive (~80% at 2500 m/day). Moreover, the D50 and
      uniformity coefficient of the particles in raw water were not the factors greatly
      affecting the filter performance. The empirical model for the filter processes of
      granular filters did not work; therefore, an empirical model towards fibre
      filters at a high flow rate was suggested, which can be used to predict the
      treatment performance. 

PMID- 26209269
TI  - The dynamics of DNA methylation and hydroxymethylation during amelogenesis.
AB  - Amelogenesis is a multistep process that relies on specific temporal and spatial
      signaling networks between the dental epithelium and mesenchymal tissues.
      Epigenetic modifications of key developmental genes in this process may be
      closely linked to a network of molecular events. However, the role of epigenetic
      regulation in amelogenesis remains unclear. Here, we have uncovered the spatial
      distributions of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) to
      determine epigenetic events in the mandibular incisors of mice.
      Immunohistochemistry and dot blotting showed that 5-hmC in ameloblasts increased
      from the secretory stage to the later maturation stage. We also demonstrated the
      distribution of 5-mC-positive ameloblasts with punctate nuclear labeling from
      sometime after the initiation of the secretory stage to the later maturation
      stage; however, dot blotting failed to detect this change. No obvious alteration
      of 5-mC/5-hmC staining in odontoblasts and dental pulp cells was observed.
      Concomitant with quantitative expression data, immunohistochemistry showed that
      maintenance DNA methyltransferase DNMT1 was highly expressed in immature dental
      epithelial cells and subsequently decreased at later stages of development.
      Meanwhile, de novo DNA methyltransferase Dnmt3a and Dnmt3b and DNA demethylase
      Tet family genes were universally expressed, except Tet1 that was highly
      expressed in immature dental epithelial cells. Thus, DNMT1 may sustain the
      undifferentiated status of dental epithelial cells through the maintenance of DNA
      methylation, while the hydroxylation of 5-mC may occur through the whole
      differentiation process by TET activity. Taken together, these data indicate that
      the dynamic changes of 5-mC and 5-hmC may be critical for the regulation of
      amelogenesis. 

PMID- 26209270
TI  - Acute and sub-chronic toxicity study of diaveridine in Wistar rats.
AB  - Diaveridine, a developed dihydrofolate reductase inhibitor, has been widely used
      as anticoccidial drug and antibacterial synergist. However, few studies have been
      performed to investigate its toxicity. To provide detailed toxicity with a wide
      spectrum of doses for diaveridine, acute and sub-chronic toxicity studies were
      conducted. Calculated LD50 was 2330 mg/kg b.w. in females and 3100 mg/kg b.w. in
      males, and chromodacryorrhea was noted in some females before their death. In the
      sub-chronic study, diaveridine was fed to Wistar rats during 90 days at dietary
      levels of 0, 23, 230, 1150 and 2000 mg/kg, which were about 0, 2.0-2.3, 21.0
      23.5, 115.2-126.9 and 212.4-217.9 mg/kg b.w., respectively. Significant decrease
      in body weights in both genders at 1150 and 2000 mg/kg groups and significant
      increases in relative weights of brain in both genders, liver in females, kidneys
      and testis in males, alkaline phosphatase and potassium in both genders at 2000
      mg/kg diet were noted. Significant decrease in absolute weights of several
      organs, hemoglobin and red blood cell count in both genders, albumin and total
      protein in females were observed at 2000 mg/kg diet. Fibroblasts in the kidneys,
      cell swelling of the glomerular zone in the adrenals and inflammation in the
      liver were found at 2000 mg/kg group. The no-observed-adverse-effect level of
      diaveridine was 230 mg/kg diet (21.0-23.5 mg/kg b.w./day).

PMID- 26209271
TI  - Racial and Ethnic Differences in Problem Gambling among College Students.
AB  - The college years are a formative period where the risk for development of
      problematic gambling is high. Research examining racial and ethnic differences in
      gambling behaviors has been limited and inconsistent. The aims of this study were
      to examine racial and ethnic differences in problem gambling among a large sample
      of college students. Undergraduates (N = 3058) from a large southern university
      completed an online screening questionnaire which included demographics, gambling
      frequency, gambling expenditure (i.e. money lost) in the previous 6 months, and
      the South Oaks Gambling Screen (SOGS). Negative binomial regression results
      indicated that Asian participants gambled less frequently than participants who
      were Caucasian or Hispanic/Latino(a), but spent more money than participants who
      were African-American (AA)/Black or Hispanic/Latino(a). A significantly larger
      proportion of Asian students met probable pathological gambling criteria (SOGS
      5+; 7.8 %) and at-risk gambling criteria (SOGS 3+; 16.3 %)) than Caucasian (5.2;
      10.1 %), AA/Black (3.9; 10.2 %), or Hispanic/Latino(a) (3.6; 9.4 %) students.
      Additionally, a significantly larger proportion of Asian students endorsed
      problematic gambling indicators such as lying about losses, feeling guilty about
      gambling, feeling like they had a gambling problem, being criticized for their
      gambling, feeling like they couldn't stop gambling, losing time from school or
      work due to gambling, having a family history of problem gambling, and arguing
      with close others about their gambling than Caucasian, AA/Black or
      Hispanic/Latino(a) students. Results suggest that Asian students may be a high
      risk sub-group of college gamblers, and that there is a critical need for
      targeted interventions for this population. 

PMID- 26209272
TI  - Child and family experiences with inborn errors of metabolism: a qualitative
      interview study with representatives of patient groups.
AB  - BACKGROUND: Patient-centered health care for children with inborn errors of
      metabolism (IEM) and their families is important and requires an understanding of
      patient experiences, needs, and priorities. IEM-specific patient groups have
      emerged as important voices within these rare disease communities and are
      uniquely positioned to contribute to this understanding. We conducted qualitative
      interviews with IEM patient group representatives to increase understanding of
      patient and family experiences, needs, and priorities and inform patient-centered
      research and care. METHODS: We developed a sampling frame of patient groups
      representing IEM disease communities from Canada, the United States, and United
      Kingdom. With consent, we interviewed participants to explore their views on
      experiences, needs, and outcomes that are most important to children with IEM and
      their families. We analyzed the data using a qualitative descriptive approach to
      identify key themes and sub-themes. RESULTS: We interviewed 18 organizational
      representatives between February 28 and September 17, 2014, representing 16 IEMs
      and/or disease categories. Twelve participants voluntarily self-identified as
      parents and/or were themselves patients. Three key themes emerged from the coded
      data: managing the uncertainty associated with raising and caring for a child
      with a rare disease; challenges associated with the affected child's life
      transitions, and; the collective struggle for improved outcomes and interventions
      that rare disease communities navigate. CONCLUSION: Health care providers can
      support children with IEM and their families by acknowledging and reducing
      uncertainty, supporting families through children's life transitions, and
      contributing to rare disease communities' progress toward improved interventions,
      experiences, and outcomes.

PMID- 26209273
TI  - Cigarette smoke-induced disruption of pulmonary barrier and bacterial
      translocation drive tumor-associated inflammation and growth.
AB  - Microorganisms have an important role in tumorgenesis by the induction of
      inflammation and by a direct impact on tumor cells. Chronic obstructive pulmonary
      disease (COPD) is associated with an increased risk for lung cancer and microbial
      colonization. We asked whether bacterial pathogens act as tumor promoters during
      CS-induced pulmonary inflammation. In a metastatic lung cancer (LC) model, Lewis
      lung carcinoma (LLC) cells were injected in mice to initiate the growth of tumors
      in the lung. Exposure to the combination of cigarette smoke (CS) and nontypeable
      Haemophilus influenzae (NTHi) synergistically increased metastatic growth. Lung
      levels of albumin and LDH, translocation of bacterial factors into tumor tissue,
      tumor inflammation, and tumor proliferation were significantly increased in mice
      exposed to CS in combination with NTHi. Bacterial pathogens increased the
      proliferation of cultured LLC cells and human cancer cell lines. Metastatic
      growth induced by the exposure to CS in combination with NTHi was reduced in mice
      deficient for IL-17. Our data provide evidence that CS-induced loss of pulmonary
      barrier integrity allows bacterial factors to translocate into tumor tissue and
      to regulate tumor-associated inflammation and tumor proliferation. Translocation
      of bacterial factors in tumor tissue links CS-induced inflammation with tumor
      proliferation. 

PMID- 26209274
TI  - NAD(P)H oxidase subunit p47phox is elevated, and p47phox knockout prevents
      diaphragm contractile dysfunction in heart failure.
AB  - Patients with chronic heart failure (CHF) have dyspnea and exercise intolerance,
      which are caused in part by diaphragm abnormalities. Oxidants impair diaphragm
      contractile function, and CHF increases diaphragm oxidants. However, the specific
      source of oxidants and its relevance to diaphragm abnormalities in CHF is
      unclear. The p47(phox)-dependent Nox2 isoform of NAD(P)H oxidase is a putative
      source of diaphragm oxidants. Thus, we conducted our study with the goal of
      determining the effects of CHF on the diaphragm levels of Nox2 complex subunits
      and test the hypothesis that p47(phox) knockout prevents diaphragm contractile
      dysfunction elicited by CHF. CHF caused a two- to sixfold increase (P < 0.05) in
      diaphragm mRNA and protein levels of several Nox2 subunits, with p47(phox) being
      upregulated and hyperphosphorylated. CHF increased diaphragm extracellular
      oxidant emission in wild-type but not p47(phox) knockout mice. Diaphragm
      isometric force, shortening velocity, and peak power were decreased by 20-50% in
      CHF wild-type mice (P < 0.05), whereas p47(phox) knockout mice were protected
      from impairments in diaphragm contractile function elicited by CHF. Our
      experiments show that p47(phox) is upregulated and involved in the increased
      oxidants and contractile dysfunction in CHF diaphragm. These findings suggest
      that a p47(phox)-dependent NAD(P)H oxidase mediates the increase in diaphragm
      oxidants and contractile dysfunction in CHF. 

PMID- 26209275
TI  - Murine and human CFTR exhibit different sensitivities to CFTR potentiators.
AB  - Development of therapeutic molecules with clinical efficacy as modulators of
      defective CFTR includes efforts to identify potentiators that can overcome or
      repair the gating defect in mutant CFTR channels. This has taken a great leap
      forward with the identification of the potentiator VX-770, now available to
      patients as "Kalydeco." Other small molecules with different chemical structure
      also are capable of potentiating the activity of either wild-type or mutant CFTR,
      suggesting that there are features of the protein that may be targeted to achieve
      stimulation of channel activity by structurally diverse compounds. However,
      neither the mechanisms by which these compounds potentiate mutant CFTR nor the
      site(s) where these compounds bind have been identified. This knowledge gap
      partly reflects the lack of appropriate experimental models to provide clues
      toward the identification of binding sites. Here, we have compared the channel
      behavior and response to novel and known potentiators of human CFTR (hCFTR) and
      murine (mCFTR) expressed in Xenopus oocytes. Both hCFTR and mCFTR were blocked by
      GlyH-101 from the extracellular side, but mCFTR activity was increased with GlyH
      101 applied directly to the cytoplasmic side. Similarly, glibenclamide only
      exhibited a blocking effect on hCFTR but both blocked and potentiated mCFTR in
      excised membrane patches and in intact oocytes. The clinically used CFTR
      potentiator VX-770 transiently increased hCFTR by ~13% but potentiated mCFTR
      significantly more strongly. Our results suggest that mCFTR pharmacological
      sensitivities differ from hCFTR, which will provide a useful tool for identifying
      the binding sites and mechanism for these potentiators. 

PMID- 26209276
TI  - Regulation of allergic lung inflammation by endothelial cell transglutaminase 2.
AB  - Tissue transglutaminase 2 (TG2) is an enzyme with multiple functions, including
      catalysis of serotonin conjugation to proteins (serotonylation). Previous
      research indicates that TG2 expression is upregulated in human asthma and in the
      lung endothelium of ovalbumin (OVA)-challenged mice. It is not known whether
      endothelial cell TG2 is required for allergic inflammation. Therefore, to
      determine whether endothelial cell TG2 regulates allergic inflammation, mice with
      an endothelial cell-specific deletion of TG2 were generated, and these mice were
      sensitized and challenged in the airways with OVA. Deletion of TG2 in endothelial
      cells blocked OVA-induced serotonylation in lung endothelial cells, but not lung
      epithelial cells. Interestingly, deletion of endothelial TG2 reduced allergen
      induced increases in respiratory system resistance, number of eosinophils in the
      bronchoalveolar lavage, and number of eosinophils in the lung tissue. Endothelial
      cell deletion of TG2 did not alter expression of adhesion molecules, cytokines,
      or chemokines that regulate leukocyte recruitment, consistent with other studies,
      demonstrating that deletion of endothelial cell signals does not alter lung
      cytokines and chemokines during allergic inflammation. Taken together, the data
      indicate that endothelial cell TG2 is required for allergic inflammation by
      regulating the recruitment of eosinophils into OVA-challenged lungs. In summary,
      TG2 functions as a critical signal for allergic lung responses. These data
      identify potential novel targets for intervention in allergy/asthma. 

PMID- 26209278
TI  - Correlation between midline gait function performance and verbal fluency in
      patients with Parkinson's disease.
AB  - BACKGROUND: Verbal fluency impairments are among the earliest and most common
      cognitive deficits in Parkinson's disease (PD), yet more than one study has shown
      that as a group, verbal fluency performance is not always different between
      patients with PD and age-matched controls. Here we examined whether PD-related
      deficits in speech and language capabilities are detectable in patients who
      exhibit poor midline motor function, such as control of gait. We postulated that
      if phonemic verbal fluency (PVF) performance in PD is dissociable from other
      factors such as age in this patient subgroup, a low PVF will likely reflect a
      general cognitive-motor deficit attributable to Parkinsonian pathology. METHODS:
      Thirty-one PD and thirteen controls were evaluated on PVF and the Metronome-Paced
      Square Step Test (MPSST), a complex sensorimotor task that challenges axial and
      midline function. The MPSST requires a patient to initiate and maintain a
      consecutive series of diagonal and midline cross-over steps during the test.
      RESULTS: We found that despite similar PVF performance between groups, the vast
      majority of controls but not patients completed the MPSST without any errors, and
      the odds of completing the MPSST without any errors was 15 times greater among
      control. More importantly, a significant amount of PVF variability was explained
      by MPSST performance in PD but not controls even after controlling for age and
      disease duration. CONCLUSION: Together, these results provide evidence that PVF
      performance in PD likely reflects a PD-specific process and suggests that the
      MPSST may be a more sensitive test of PD-specific pathology than PVF.

PMID- 26209277
TI  - Protocadherin-1 binds to SMAD3 and suppresses TGF-beta1-induced gene
      transcription.
AB  - Genetic studies have identified Protocadherin-1 (PCDH1) and Mothers against
      decapentaplegic homolog-3 (SMAD3) as susceptibility genes for asthma. PCDH1 is
      expressed in bronchial epithelial cells and has been found to interact with SMAD3
      in yeast two-hybrid (Y2H) overexpression assays. Here, we test whether PCDH1 and
      SMAD3 interact at endogenous protein levels in bronchial epithelial cells and
      evaluate the consequences thereof for transforming growth factor-beta1 (TGF
      beta1)-induced gene transcription. We performed Y2H screens and
      coimmunoprecipitation (co-IP) experiments of PCDH1 and SMAD3 in HEK293T and
      16HBE14o(-) (16HBE) cell lines. Activity of a SMAD3-driven luciferase reporter
      gene in response to TGF-beta1 was measured in BEAS-2B cells transfected with
      PCDH1 and in 16HBE cells transfected with PCDH1-small-interfering RNA (siRNA).
      TGF-beta1-induced gene expression was quantified in BEAS-2B clones overexpressing
      PCDH1 and in human primary bronchial epithelial cells (PBECs) transfected with
      PCDH1-siRNA. We confirm PCDH1 and SMAD3 interactions by Y2H and by co-IP in
      HEK293T cells overexpressing both proteins, and at endogenous protein levels in
      16HBE cells. TGF-beta-induced activation of a SMAD3-driven reporter was reduced
      by exogenous PCDH1 in BEAS2B cells, whereas it was increased by siRNA-mediated
      knockdown of endogenous PCDH1 in 16HBE cells. Overexpression of PCDH1 suppressed
      expression of TGF-beta target genes in BEAS-2B cells, whereas knockdown of PCDH1
      in human PBECs increased TGF-beta-induced gene expression. In conclusion, we
      demonstrate that PCDH1 binds to SMAD3 and regulates its activation by TGF-beta
      signaling in bronchial epithelial cells. We propose that PCDH1 and SMAD3 act in a
      single pathway in asthma susceptibility that affects sensitivity of the airway
      epithelium to TGF-beta. 

PMID- 26209279
TI  - Neck fracture of femoral stems with a sharp slot at the neck: biomechanical
      analysis.
AB  - BACKGROUND: Fracture of the femoral stem in total hip arthroplasty (THA) is a
      rare complication. We have encountered 2 cases of neck fractures of the femoral
      stem occurring 9 and 12 years after THA. Morphological and biomechanical analysis
      were performed to investigate the mechanism of these fractures. METHOD: A
      titanium alloy femoral stem having a slot with sharp corners (R = 0.2 mm) at the
      neck had been implanted in both cases. Fracture surfaces were examined by use of
      scanning electron microscopy (SEM). Stress concentration was simulated by using a
      finite element method (FEM) to compare slots with sharp (R = 0.2 mm) and smooth
      (R = 2 mm) corners. RESULTS: Study of the retrieved stems revealed that neck
      fractures had occurred at the distal end of the slot in both cases. SEM revealed
      numerous fine fissures extending from the anterolateral edge, striations on the
      middle of the fracture surface, and dimples on the posteromedial surface,
      suggesting that the fractures had occurred from the anterolateral aspect toward
      the posteromedial aspect because of metallic fatigue. FEM analysis showed that
      mechanical stress was concentrated at the distal and anterolateral corners of the
      slot. Under 3500-N loading force, the stress at the sharp corner was 556 MPa,
      which was approximately twofold that at the smooth corner and exceeded the
      fatigue strength of titanium alloy. CONCLUSION: These findings showed that the
      sharp corner of slot increased stress concentrations at the anterolateral aspect
      and led to the neck fractures.

PMID- 26209280
TI  - Mandatory Intensivist Management Decreases Length of Stay, Facilitates an
      Increase in Admissions and Minimizes Closure of a Neurocritical Care Unit.
AB  - BACKGROUND: The primary objectives of this study were to identify patient and
      community benefits of mandatory intensivist management in a neurocritical care
      (NCC) unit. Our hospital recently mandated intensivist management for patients
      admitted to the NCC unit. As one of the only comprehensive stroke centers in
      Orlando, an unacceptably high number of patients were being denied admission
      because of overcapacity. We compared length of stay (LOS), complications,
      outcomes, total admissions, and emergency transfer center closure rates before
      and after implementation of mandatory intensivist management. METHODS: A
      retrospective review comparing 1551 patients admitted to a 20 bed NCC unit from
      November 1, 2009 to October 31, 2010 (prior to mandatory intensivist management)
      with 1702 patients admitted from January 1, 2011 to December 31, 2011 (after the
      requirement) was performed. This included examining LOS, Acute Physiology and
      Chronic Health Evaluation III (APACHE) scores, service line closure rates, and
      mortality during both time periods. RESULTS: Analysis revealed that despite
      comparable APACHE scores, implementation of mandatory intensivist management
      reduced overall NCC LOS, 4.6 versus 3.7 days, (p < 0.01) and increased the number
      of monthly admissions, 129 versus 142, (p = 0.02). The percentage of patients
      declined admission because of a closed service line was reduced from 12.36 to
      5.66 %, (p = 0.02). Mortality and infection rates remained unchanged.
      CONCLUSIONS: Implementation of mandatory intensivist management in the NCC unit
      decreased LOS, increased admissions, and decreased service line closure rates,
      while maintaining patient care.

PMID- 26209281
TI  - Accuracy of Daily Lung Ultrasound for the Detection of Pulmonary Edema Following
      Subarachnoid Hemorrhage.
AB  - BACKGROUND: Early detection of pulmonary edema is vital to appropriate fluid
      management following subarachnoid hemorrhage (SAH). Lung ultrasound (LUS) has
      been shown to accurately identify pulmonary edema in patients with acute
      respiratory failure (ARF). Our objective was to determine the accuracy of daily
      screening LUS for the detection of pulmonary edema following SAH. METHODS:
      Screening LUS was performed in conjunction with daily transcranial doppler for
      SAH patients within the delayed cerebral ischemia (DCI) risk period in our
      neuroICU. We reviewed records of SAH patients admitted 7/2012-5/2014 who
      underwent bilateral LUS on at least 5 consecutive days. Ultrasound videos were
      reviewed by an investigator blinded to the final diagnosis. "B+ lines" were
      defined as >=3 B-lines on LUS. Two other investigators blinded to ultrasound
      results determined whether pulmonary edema with ARF (PE-ARF) was present during
      the period of evaluation on the basis of independent chart review, with a fourth
      investigator performing adjudication in the event of disagreement. The diagnostic
      accuracy of B+ lines for the detection of PE-ARF and RPE was determined. RESULTS:
      Of 59 patients meeting criteria for inclusion, 21 (36%) had PE-ARF and 26 (44%)
      had B+ lines. Kappa for inter-rater agreement was 0.821 (p < 0.0001) for clinical
      diagnosis of PE-ARF between the two investigators. B+ lines demonstrated
      sensitivity 90% (95% CI 70-99%) and specificity 82% (66-92%), for PE-ARF. Median
      days from B+ lines onset to PE-ARF was 1 (IQR 0-1). CONCLUSION: Screening LUS was
      a sensitive test for the detection of symptomatic pulmonary edema following SAH
      and may assist with fluid titration during the risk period for DCI.

PMID- 26209282
TI  - Assessment of arsenic (As) occurrence in arable soil and its related health risk
      in China.
AB  - Arsenic (As) is a major global environmental pollutant due to its high toxicity
      on human and animal health. This study collected 427 relevant papers to study As
      concentrations in Chinese arable soil and evaluate the health risk of exposure to
      As for humans. Results showed that the average of As concentration was 9.46 mg/kg
      in Chinese arable soil. Soil As concentrations in Hunan Province and Guangxi
      Zhuang Autonomous Region posed high carcinogenic and non-cancer risks on human
      health through diet, Yunnan, Guizhou, Guangdong, and Xinjiang provinces had
      relative high health risks, while As concentrations in the other provinces posed
      low health risks on humans. The physical factors controlled the spatial pattern
      of health risk on a provincial scale, but the As-related human activities
      introduced high health risk on people, particularly the agricultural activities
      such as sewage irrigation and fertilizer application should be given more
      attention due to its large area. 

PMID- 26209284
TI  - Erratum to: Cutaneous Phaeohyphomycosis Caused by Exophiala attenuata in a
      Domestic Cat.

PMID- 26209283
TI  - Tactile event-related potentials in amyotrophic lateral sclerosis (ALS):
      Implications for brain-computer interface.
AB  - OBJECTIVE: We investigated neurophysiological brain responses elicited by a
      tactile event-related potential paradigm in a sample of ALS patients. Underlying
      cognitive processes and neurophysiological signatures for brain-computer
      interface (BCI) are addressed. METHODS: We stimulated the palm of the hand in a
      group of fourteen ALS patients and a control group of ten healthy participants
      and recorded electroencephalographic signals in eyes-closed condition. Target and
      non-target brain responses were analyzed and classified offline. Classification
      errors served as the basis for neurophysiological brain response sub-grouping.
      RESULTS: A combined behavioral and quantitative neurophysiological analysis of
      sub-grouped data showed neither significant between-group differences, nor
      significant correlations between classification performance and the ALS patients'
      clinical state. Taking sequential effects of stimuli presentation into account,
      analyses revealed mean classification errors of 19.4% and 24.3% in healthy
      participants and ALS patients respectively. CONCLUSIONS: Neurophysiological
      correlates of tactile stimuli presentation are not altered by ALS. Tactile event
      related potentials can be used to monitor attention level and task performance in
      ALS and may constitute a viable basis for future BCIs. SIGNIFICANCE: Implications
      for brain-computer interface implementation of the proposed method for patients
      in critical conditions, such as the late stage of ALS and the (completely) locked
      in state, are discussed.

PMID- 26209285
TI  - Hypersialorrhea in Wilson's Disease.
AB  - Hypersialorrhea, corresponding to excessive salivation is a symptom frequently
      reported in Wilson's disease, especially in its neurological form. The prevalence
      of this frequent complaint has not been often evaluated. During a 7-month period,
      87 consecutive Wilson's disease patients answered to the simple question "do you
      have the sensation of excess saliva in your mouth?" to evaluate the frequency of
      this symptom. A sub-sample of 10 consecutive Wilson's disease patients with
      drooling was recruited to undergo quantitative and qualitative measures to
      evaluate the mechanism of hypersialorrhea. Excessive drooling or excess saliva
      was found in 46 % of patients followed at the French Reference Centre. Ninety
      eight percent of them presented neurological symptoms and drooling was found in
      only one patient without neurological symptoms. Our study showed that patients
      with a complaint of excessive saliva produced significantly higher quantities of
      saliva at rest than controls. Endoscopic examination was abnormal in six
      patients. A significant decrease of swallowing frequency, longer swallow
      latencies, and poor swallowing capacities may partly explain the salivary stasis.
      Oropharyngeal sensitivity disorders were present in 50 % of our patients. The
      decrease of the swallowing frequency observed in all patients could be related to
      cognitive and behavioral abnormalities with initiation difficulties objectified
      by longer latencies triggered by all the ingested volumes. This study confirmed
      the hypothesis of a multifactorial origin of hypersialorrhea in patients who have
      been diagnosed in Wilson's disease. It was essential to evaluate drooling with a
      multidisciplinary consultation to better identify the underlying mechanisms and
      to implement strategies for speech therapy and therapeutic adaptation.

PMID- 26209286
TI  - Identifying Patterns of FEES-Derived Swallowing Trajectories Using Group-Based
      Trajectory Model.
AB  - The present study delineates and visualizes swallowing trajectories along seven
      swallow trials in dysphagic patients using group-based trajectory modeling
      (GBTM). This model facilitates the recognition of swallowing functional
      categories, estimates their frequency of occurrence, and enhances the
      understanding of swallowing dynamics. Two hundred and five dysphagic patients
      underwent a standardized FEES examination protocol. Five ordinal variables were
      blindly assessed for each swallow by two observers independently. GBTM analysis
      was conducted to find and characterize trajectories of FEES responses. For most
      FEES outcome variables, trajectories were qualitatively distinct in degree and
      kind (level of impairment and how this changed over the seven swallow trials).
      Two FEES outcome variables-delayed initiation of the pharyngeal reflex and
      postswallow pyriform sinus pooling-showed the highest prevalence of severe
      swallowing impairment. Highly impaired categories were more stable throughout the
      different swallow trials. Intermediate trajectories, by contrast, were erratic,
      responding more sensitively to shifts in bolus consistency. GBTM can identify
      distinct developmental trajectories of measured FEES variables in patients with
      oropharyngeal dysphagia. In clinical practice, classification into distinct
      groups would help to identify the subgroup of dysphagic patients who may need
      specific medical attention.

PMID- 26209287
TI  - Direct, Cementless, Metaphyseal Fixation in Knee Revision Arthroplasty With
      Sleeves-Short-Term Results.
AB  - Different options for implant fixation in revision TKA exist. Small series have
      been published on direct cementless fixation with sleeves. The objective of this
      study was to analyze the short- and mid-term results of sleeve-fixation in a
      large revision TKA series. In this prospective study 121 patients with 193
      sleeves (119 tibial and 74 femoral) were included. Mean follow-up was 3.6 years
      (2-6.1 years). Analysis included clinical and radiographic assessment. ROM, KSS
      and Functional Score improved significantly. Fourteen patients (11.4%) underwent
      operative re-revision during the follow-up period. Direct cementless fixation in
      the metaphysis by sleeves is a promising option for implant fixation in revision
      TKA, both on the tibial and femoral side.

PMID- 26209288
TI  - In reply.

PMID- 26209289
TI  - The Other Path-Think Radial.

PMID- 26209290
TI  - Physiologically Based Pharmacokinetic Predictions of Tramadol Exposure Throughout
      Pediatric Life: an Analysis of the Different Clearance Contributors with Emphasis
      on CYP2D6 Maturation.
AB  - This paper focuses on the retrospective evaluation of physiologically based
      pharmacokinetic (PBPK) techniques used to mechanistically predict clearance
      throughout pediatric life. An intravenous tramadol retrograde PBPK model was set
      up in Simcyp(r) using adult clearance values, qualified for CYP2D6, CYP3A4,
      CYP2B6, and renal contributions. Subsequently, the model was evaluated for
      mechanistic prediction of total, CYP2D6-related, and renal clearance predictions
      in very early life. In two in vitro pediatric human liver microsomal (HLM)
      batches (1 and 3 months), O-desmethyltramadol and N-desmethyltramadol formation
      rates were compared with CYP2D6 and CYP3A4 activity, respectively. O
      desmethyltramadol formation was mediated only by CYP2D6, while N
      desmethyltramadol was mediated in part by CYP3A4. Additionally, the clearance
      maturation of the PBPK model predictions was compared to two in vivo maturation
      models (Hill and exponential) based on plasma concentration data, and to
      clearance estimations from a WinNonlin(r) fit of plasma concentration and urinary
      excretion data. Maturation of renal and CYP2D6 clearance is captured well in the
      PBPK model predictions, but total tramadol clearance is underpredicted. The most
      pronounced underprediction of total and CYP2D6-mediated clearance was observed in
      the age range of 2-13 years. In conclusion, the PBPK technique showed to be a
      powerful mechanistic tool capable of predicting maturation of CYP2D6 and renal
      tramadol clearance in early infancy, although some underprediction occurs between
      2 and 13 years for total and CYP2D6-mediated tramadol clearance. 

PMID- 26209292
TI  - Peripheral proinflammatory markers associated with ketamine response in a
      preclinical model of antidepressant-resistance.
AB  - Ketamine, N-methyl-d-aspartate (NMDA) receptor antagonist and anti-inflammatory
      agent, has rapid therapeutic effects in a subset of patients with more
      intractable forms of depression. Irregular proinflammatory cytokine and acute
      reactive protein levels have been reported in clinical and preclinical depression
      research. We explored the association between the rapid antidepressant-like
      effects of ketamine and peripheral proinflammatory profile in a model of
      antidepressant-resistance. Male Wistar rats were pre-treated with ACTH-(1-24)
      100MUg/d or saline (0.9%) for 14d. Antidepressant-like effects were assessed with
      the forced swim test (FST). Ketamine (10mg/kg) significantly reduced immobility
      duration in saline-pretreated control animals. In contrast, a divergent response
      was observed in ACTH-pretreated antidepressant resistant animals, with 50%
      responders and 50% non-responders. Plasma samples were analyzed via enzyme-linked
      immunosorbent assay (ELISA) for interleukin 6 (IL-6), tumour necrosis factor
      alpha (TNFalpha) and C-reactive protein (CRP). Levels of CRP and TNFalpha
      differentiated ketamine responders and non-responders. 

PMID- 26209291
TI  - Contribution of the IL-17 Pathway to Psoriasis and Psoriatic Arthritis.
AB  - Investigators have accrued compelling evidence that the IL-17 pathway is central
      to the pathogenesis of psoriasis and psoriatic arthritis. The evidence comprises
      genome-wide association studies (GWAS), data from experimental murine models and
      findings from in vitro studies on patients' cells or tissue biopsies. More
      recently, the success of drugs blocking the IL-17 pathway in treating both
      psoriasis (PsO) and psoriatic arthritis (PsA) confirms that IL-17 is a clinically
      relevant therapeutic target. However, there remain many unanswered questions: is
      PsA simply an extension of PsO from the skin to the synovial tissue or are there
      differences in the underlying pathogenesis of these diseases? Which cell type
      represents the primary source of IL-17 in PsO and PsA? And how are these cells
      regulated? This review outlines the IL-17 pathway, summarises the evidence
      supporting its role in PsO and PsA and discusses recent data that may help to
      address these yet unresolved questions.

PMID- 26209293
TI  - The time-dependent and persistent effects of amphetamine treatment upon recovery
      from hemispatial neglect in rats.
AB  - Neglect is a neuropsychological disorder characterized by the failure to report
      or respond to stimuli presented to the side of the body opposite a brain lesion
      and occurs in approximately 40% of right hemisphere strokes. The need for
      effective therapies to treat neglect in humans has led to the development of a
      rodent model. Unilateral destruction of medial agranular cortex (AGm), which is
      part of a cortical network for directed attention, produces severe multimodal
      neglect with deficits similar to those seen in humans. Amphetamines have
      previously been investigated for inducing plasticity and recovery of function
      following brain damage. Amphetamine treatment has been shown to produce recovery
      from visual, frontal, and sensorimotor cortex damage in animals and this recovery
      may be the result of axonal growth originating from the opposite, unlesioned
      hemisphere. The purpose of this study was to investigate whether amphetamine
      treatment would induce recovery from neglect produced by unilateral AGm
      destruction, the time frame in which amphetamine must be administered in order to
      be effective, and the permanence of recovery following treatment. The results
      indicated that subjects injected with 2mg/kg of d-amphetamine on days 0, 2, and 5
      recovered in significantly fewer days than saline-treated controls, even when
      administration was delayed by 2 and 7 days. Additionally, these studies indicated
      that recovery persisted for at least 60 days suggesting that recovery is likely
      to be long term. 

PMID- 26209295
TI  - Fluorouracil induces autophagy-related gastric carcinoma cell death through
      Beclin-1 upregulation by miR-30 suppression.
AB  - The molecular mechanisms underlying the anti-cancer effects of chemotherapy drugs
      are not completely understood. Here, we studied the effects of fluorouracil (5
      FU) on gastric carcinoma (GC) cells. We found that 5-FU dose-dependently
      inhibited the growth of GC cells, in either a cell counting kit-8 (CCK-8) assay
      or a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
      Moreover, autophagy-associated protein 6 (ATG6) or Beclin-1 was dose-dependently
      activated by 5-FU in GC cells. Further, microRNA (miR)-30 was found to be
      regulated by 5-FU, and bioinformatics analysis showed that miR-30 targeted the 3'
      UTR of Beclin-1 to inhibit its translation. Together, these data suggest that 5
      FU may suppress miR-30 to upregulate Beclin-1 to induce autophagic cell death and
      cell proliferation arrest in GC cells.

PMID- 26209294
TI  - Salinomycin radiosensitizes human nasopharyngeal carcinoma cell line CNE-2 to
      radiation.
AB  - Nasopharyngeal carcinoma (NPC) is primarily treated by chemoradiation. However,
      how to promote radiation sensitivity in NPC remains a challenge. Salinomycin is
      potentially useful for the treatment of cancer. This study aimed to explore the
      radiosensitivity of salinomycin on human nasopharyngeal carcinoma cell line CNE
      2. CNE-2 were treated with salinomycin or irradiation, alone or in combination.
      The cytotoxicity effects of salinomycin were measured using CCK-8 assay.
      Clonogenic survival assay was used to evaluate the effects of salinomycin on the
      radiosensitivity of CNE-2. The changes of cell cycle distribution and apoptosis
      were assayed using flow cytometry. The expression of Caspase3/Bax/Bal-2 was
      detected by Western blotting. DNA damage was detected via gamma-H2AX foci
      counting. The results showed that salinomycin induced apoptosis and G2/M arrest,
      increased Bax and cleaved Caspase3, decreased Bcl-2 expression, and increased the
      formation of gamma-H2AX nuclear foci. These data suggest that salinomycin may be
      a radiosensitizer for NPC radiotherapy. 

PMID- 26209296
TI  - RETRACTED ARTICLE: Profiles of tissue microRNAs; miR-148b and miR-25 serve as
      potential prognostic biomarkers for hepatocellular carcinoma.

PMID- 26209297
TI  - Ethnomedicinal uses of Edible Wild Fruits (EWFs) in Swat Valley, Northern
      Pakistan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This study documents the ethno-pharmacological
      importance of Edible Wild Fruits (EWFs) resource in the wild floral emporium of
      Swat, Khyber Pakhtunkhwa Northern Pakistan. This is imitated in the great
      diversity of plants used for medicinal purposes as well as in their wide range of
      therapeutic applications. METHODS: Ethnomedicinal data was collected through semi
      structured and open ended interviews, questionnaires, field surveys and local
      gatherings. Use value (UV), Relative importance (RI), Relative frequency of
      citation (RFC), Informant consensus factor (ICF) and Family importance value
      (FIV) was calculated to elaborate the EWFs, their families, disease treated and
      significant fruit species based on use reports by informants. RESULTS: A total of
      47 species of EWFs belonging to 32 genera and 23 families were reported to be
      used in traditional medicines. Family Rosaceae dominated with 26% species
      followed by Moraceae (12%) and Rhamnaceae (10%), with mostly tree type of growth
      form (55%). The most consumed part of plants was fruit (72%) followed by leaves
      (21%). Decoction (26%) and unprocessed fruit (24%) were the major modes of crude
      drug preparation. The Informant consensus factor (ICF) of Joint/body aches was
      the highest followed by digestive disorders. Use value index of Vitis vinifera
      (3.8), being the highest, followed by Malus pumila (2) and Vitis parvifolia (2).
      CONCLUSION: The tradition of using EWFs in treating ailments is a common practice
      among the tribal communities, depending on the socio-economic conditions of the
      people. The multiple uses of these EWFs suggest further investigation regarding
      phytochemical analysis and pharmaceutical applications.

PMID- 26209298
TI  - Improving Electrical Conductivity, Thermal Stability, and Solubility of
      Polyaniline-Polypyrrole Nanocomposite by Doping with Anionic Spherical
      Polyelectrolyte Brushes.
AB  - The extent to which anionic spherical polyelectrolyte brushes (ASPB) as dopant
      improved the performance of polyaniline-polypyrrole (PANI-PPy) nanocomposite was
      investigated. Different characterization and analytical methods including Fourier
      transform infrared spectroscopy (FTIR), thermo-gravimetric analysis (TGA),
      scanning electron microscopy (SEM), and X-ray diffraction (XRD) confirmed that
      ASPB serving as dopant could improve the comprehensive properties of PANI-PPy
      nanocomposite. It was different from dopants such as SiO2, poly(sodium-p
      styrenesulfonate) (PSS), and canonic spherical polyelectrolyte brushes (CSPB)
      which only enhanced the performance of PANI-PPy nanocomposite on one or two
      sides. The electrical conductivity of (PANI-PPy)/ASPB nanocomposite at room
      temperature was 8.3 S/cm, which was higher than that of PANI-PPy (2.1 S/cm),
      (PANI-PPy)/PSS (6.8 S/cm), (PANI-PPy)/SiO2 (7.2 S/cm), and (PANI-PPy)/CSPB (2.2
      S/cm). Meanwhile, (PANI-PPy)/ASPB nanocomposite possessed enhanced thermal
      stability and good solubility. In addition, the effects of polymerization
      temperature, the molecular weight of grafted polyelectrolyte brushes, and storage
      time on electrical conductivity were discussed. 

PMID- 26209299
TI  - Statistical analysis of land surface temperature-vegetation indexes relationship
      through thermal remote sensing.
AB  - Vegetation coverage has a significant influence on the land surface temperature
      (LST) distribution. In the field of urban heat islands (UHIs) based on remote
      sensing, vegetation indexes are widely used to estimate the LST-vegetation
      relationship. This paper devises two objectives. The first analyzes the
      correlation between vegetation parameters/indicators and LST. The subsequent
      computes the occurrence of vegetation parameter, which defines the distribution
      of LST (for quantitative analysis of urban heat island) in Kalaburagi (formerly
      Gulbarga) City. However, estimation work has been done on the valuation of the
      relationship between different vegetation indexes and LST. In addition to the
      correlation between LST and the normalized difference vegetation index (NDVI),
      the normalized difference build-up index (NDBI) is attempted to explore the
      impacts of the green land to the build-up land on the urban heat island by
      calculating the evaluation index of sub-urban areas. The results indicated that
      the effect of urban heat island in Kalaburagi city is mainly located in the sub
      urban areas or Rurban area especially in the South-Eastern and North-Western part
      of the city. The correlation between LST and NDVI, indicates the negative
      correlation. The NDVI suggests that the green land can weaken the effect on urban
      heat island, while we perceived the positive correlation between LST and NDBI,
      which infers that the built-up land can strengthen the effect of urban heat
      island in our case study. Although satellite data (e.g., Landsat TM thermal bands
      data) has been applied to test the distribution of urban heat islands, but the
      method still needs to be refined with in situ measurements of LST in future
      studies. 

PMID- 26209300
TI  - Assessment of electrocardiographic parameters in patients with electrocution
      injury.
AB  - BACKGROUND: Electrocution injury (EI) is a major problem in developing countries.
      The aim of this study is to investigate the effect of EI on electrocardiographic
      (ECG) parameters. METHODS: A total of 43 patients hospitalized with diagnosis of
      EI were prospectively enrolled. Admission ECGs were compared with follow-up ECGs
      obtained one month after the event. RESULTS: Maximum P wave duration (Pmax),
      minimum P wave duration (Pmin), P wave dispersion (PWD), PR interval, QRS complex
      duration, corrected QT duration (QTc), QT dispersion (QTD), T peak to T end (Tp
      e) interval were longer and Tp-e interval/QT and Tp-e interval/QTc ratios were
      higher on admission ECGs compared to follow-up ECGs. Frontal QRS-T angle and
      frequency of patients with fragmented QRS were also higher on admission ECGs.
      CONCLUSION: Our study revealed that EI causes significant deterioration of
      admission ECG parameters. The clinical use of these parameters in prediction of
      arrhythmias after EI warrants further studies.

PMID- 26209301
TI  - Virtual collaboration: effect of spatial configuration on spatial statements
      production.
AB  - When guiding a remote collaborator in a virtual environment, people often take an
      addressee-perspective, which may have a high cognitive cost. In order to improve
      collaborative virtual environments, a better understanding of how operators share
      spatial information is needed. This work aimed to study the cognitive workload
      linked to spatial statements production in situations in which the relative
      positions of speaker, addressee and target were varied. Twenty-two participants
      were asked to give--in one go--instructions to a virtual collaborator on how to
      find a target in a 3D environment. The scene showed an avatar in the center of
      eight tables. Sixty-four configurations of avatar orientation (eight
      possibilities) and target location (on the eight tables) were tested. We measured
      the delay in starting the instruction once the target appeared, the instruction
      duration and the subjective evaluation of mental demand. Each instruction was
      classified according to the spatial reference frame used. The delay was
      influenced by the processing of spatial information in ego-centered and addressee
      centered reference frames. All subsequent measures were determined by mental
      transformations in addressee-centered coordinates. One condition in particular,
      when the target was situated diagonally behind the addressee, gave rise to a
      higher mental demand for the speaker, which points to the investment made by the
      speaker in achieving the least collaborative effort. Further work should seek to
      develop efficient tools to facilitate spatial communication in situations that
      induce the most mental workload.

PMID- 26209302
TI  - Combined effects of expectations and visual uncertainty upon detection and
      identification of a target in the fog.
AB  - Detecting a pedestrian while driving in the fog is one situation where the prior
      expectation about the target presence is integrated with the noisy visual input.
      We focus on how these sources of information influence the oculomotor behavior
      and are integrated within an underlying decision-making process. The participants
      had to judge whether high-/low-density fog scenes displayed on a computer screen
      contained a pedestrian or a deer by executing a mouse movement toward the
      response button (mouse-tracking). A variable road sign was added on the scene to
      manipulate expectations about target identity. We then analyzed the timing and
      amplitude of the deviation of mouse trajectories toward the incorrect response
      and, using an eye tracker, the detection time (before fixating the target) and
      the identification time (fixations on the target). Results revealed that
      expectation of the correct target results in earlier decisions with less
      deviation toward the alternative response, this effect being partially explained
      by the facilitation of target identification.

PMID- 26209303
TI  - Reply.

PMID- 26209304
TI  - Research With Children Exposed to Partner Violence: Perspectives of Service
      Mandated, CPS- and Court-Involved Survivors on Research With Their Children.
AB  - Rapidly growing numbers of female survivors of intimate partner violence (IPV)
      who are the primary caregivers for their children are being mandated to services
      by child protective services (CPS) and/or the court system. Research is needed to
      better understand the experiences of these children; however, such research is
      hindered by the dearth of empirical evidence to guide researchers in how best to
      recruit and collect data about and from IPV-exposed children whose families are
      mandated to services. From a qualitative study with 21 CPS- and/or court-involved
      mothers, this article reports findings about participants' perspectives regarding
      research with their IPV-exposed children. Our analyses determined three key
      findings: (a) mothers' reasons or motivations for allowing their children to
      participate in research, (b) mothers' reasons for refusing consent for their
      children to participate, and (c) strategies for increasing research participation
      among this population. Based on these findings, we offer recommendations for
      enhancing research participation among IPV-exposed children from CPS- and/or
      court-involved families mandated to services, including specific recruitment and
      data collection strategies. These recommendations and strategies also hold value
      for research with other vulnerable families and children struggling with
      violence.

PMID- 26209305
TI  - The Impact of Polyvictimization on Delinquency Among Latino Adolescents: A
      General Strain Theory Perspective.
AB  - Although criminological research has provided support for general strain theory
      (GST), there is still little known about the relationship between victimization
      and delinquency among Latino adolescents. This study seeks to fill the gap in the
      literature by examining the association between a broader measure of
      victimization (i.e., polyvictimization) and delinquent behavior using data from
      the Dating Violence Among Latino Adolescents (DAVILA) Study, a national sample of
      Latino youth. Logistic regression analyses were conducted to examine two issues:
      (a) whether polyvictimization is associated with self-reported delinquent
      behavior and (b) whether anger mediates the relationship between
      polyvictimization and delinquency. Our findings provided partial support for GST
      among Latino youth. Specifically, the effect of polyvictimization on delinquency
      was explained in part by its effect on anger. Contrary to the theory's
      hypothesis, the effect of polyvictimization was not conditional on the effect of
      social support. Overall, findings suggested that GST is a promising framework for
      understanding the relationship between polyvictimization and delinquency among
      Latino youth.

PMID- 26209306
TI  - Socioemotional Problems in Children Exposed to Intimate Partner Violence:
      Mediating Effects of Attachment and Family Supports.
AB  - Given the high likelihood of women remaining with their partner when intimate
      partner violence (IPV) is present, it is important to work with existing family
      strengths and social supports to minimize emotional harm to the children of these
      couples. The current study involved interviews with mothers of young children in
      the child welfare system across a state in the northeast ( n = 336). Roughly one
      third of these women reported IPV in the past year. The relationship between IPV
      and child socioemotional problems was explored, along with supports that might
      mediate this relationship. Study results showed that child exposure to IPV was
      directly related to socioemotional problems. This was mediated by three family
      and social factors: strength of mother-child attachment, overall family
      functioning, and level of mothers' emotional support. Findings revealed the
      heterogeneity among families with IPV and highlight the need for interventions
      focused on the ecological context in which women are parenting.

PMID- 26209307
TI  - What Is the Attraction? Pornography Use Motives in Relation to Bystander
      Intervention.
AB  - Use of pornography is common among adolescents and young adults, with most men
      and a growing number of women viewing regularly. A vast body of research suggests
      pornography use is associated with multiple attitudinal and behavioral variables.
      One of those associations, for both men and women, is higher pornography use is
      correlated with a lower likelihood of intervening to prevent sexual assault. The
      present study explored how motives for viewing pornography related to male ( n =
      139) and female ( n = 290) college students' willingness and efficacy to
      intervene to help prevent a sexual assault from occurring. We found that several
      motivations to view pornography were associated with suppression of willingness
      to intervene as a bystander, even after controlling for frequency of pornography
      use. This study joins others in suggesting an association between pornography use
      and callousness toward sexual violence.

PMID- 26209308
TI  - Domestic and Marital Violence Among Three Ethnic Groups in Nigeria.
AB  - There is evidence that between half and two thirds of Nigerian women have
      experienced domestic violence, and that this is higher in some ethnic groups than
      others. Yet, studies that examine the ethnic dimensions of domestic and marital
      violence are conspicuously missing in the literature. We fill this void using
      data from the Nigeria Demographic and Health Survey. Results indicate significant
      ethnic differences with Igbo women more likely to have experienced sexual and
      emotional violence compared with Yoruba women. Hausa women were however
      significantly less likely to experience physical and sexual violence but not
      emotional violence, compared with Yoruba women. Women with domineering husbands
      were significantly more likely to experience physical, sexual, and emotional
      violence. Similarly, those who thought wife-beating was justified were more
      likely to experience all three types of violence. The independent effects of
      ethnicity on domestic violence suggests that specific interventions may be needed
      for women belonging to different ethnic groups if the problem of domestic
      violence is to be dealt with effectively in Nigeria.

PMID- 26209309
TI  - Human metabolic atlas: an online resource for human metabolism.
AB  - Human tissue-specific genome-scale metabolic models (GEMs) provide comprehensive
      understanding of human metabolism, which is of great value to the biomedical
      research community. To make this kind of data easily accessible to the public, we
      have designed and deployed the human metabolic atlas (HMA) website
      (http://www.metabolicatlas.org). This online resource provides comprehensive
      information about human metabolism, including the results of metabolic network
      analyses. We hope that it can also serve as an information exchange interface for
      human metabolism knowledge within the research community. The HMA consists of
      three major components: Repository, Hreed (Human REaction Entities Database) and
      Atlas. Repository is a collection of GEMs for specific human cell types and human
      related microorganisms in SBML (System Biology Markup Language) format. The
      current release consists of several types of GEMs: a generic human GEM, 82 GEMs
      for normal cell types, 16 GEMs for different cancer cell types, 2 curated GEMs
      and 5 GEMs for human gut bacteria. Hreed contains detailed information about
      biochemical reactions. A web interface for Hreed facilitates an access to the
      Hreed reaction data, which can be easily retrieved by using specific keywords or
      names of related genes, proteins, compounds and cross-references. Atlas web
      interface can be used for visualization of the GEMs collection overlaid on KEGG
      metabolic pathway maps with a zoom/pan user interface. The HMA is a unique tool
      for studying human metabolism, ranging in scope from an individual cell, to a
      specific organ, to the overall human body. This resource is freely available
      under a Creative Commons Attribution-NonCommercial 4.0 International License.

PMID- 26209310
TI  - SHIELD: an integrative gene expression database for inner ear research.
AB  - The inner ear is a highly specialized mechanosensitive organ responsible for
      hearing and balance. Its small size and difficulty in harvesting sufficient
      tissue has hindered the progress of molecular studies. The protein components of
      mechanotransduction, the molecular biology of inner ear development and the
      genetic causes of many hereditary hearing and balance disorders remain largely
      unknown. Inner-ear gene expression data will help illuminate each of these areas.
      For over a decade, our laboratories and others have generated extensive sets of
      gene expression data for different cell types in the inner ear using various
      sample preparation methods and high-throughput genome-wide approaches. To
      facilitate the study of genes in the inner ear by efficient presentation of the
      accumulated data and to foster collaboration among investigators, we have
      developed the Shared Harvard Inner Ear Laboratory Database (SHIELD), an
      integrated resource that seeks to compile, organize and analyse the genomic,
      transcriptomic and proteomic knowledge of the inner ear. Five datasets are
      currently available. These datasets are combined in a relational database that
      integrates experimental data and annotations relevant to the inner ear. The
      SHIELD has a searchable web interface with two data retrieval options: viewing
      the gene pages online or downloading individual datasets as data tables. Each
      retrieved gene page shows the gene expression data and detailed gene information
      with hyperlinks to other online databases with up-to-date annotations.
      Downloadable data tables, for more convenient offline data analysis, are derived
      from publications and are current as of the time of publication. The SHIELD has
      made published and some unpublished data freely available to the public with the
      hope and expectation of accelerating discovery in the molecular biology of
      balance, hearing and deafness.

PMID- 26209311
TI  - In vitro pharmacodynamics of fosfomycin against clinical isolates of Pseudomonas
      aeruginosa.
AB  - BACKGROUND: The use of fosfomycin for treatment of systemic infections due to MDR
      Pseudomonas aeruginosa is increasing. However, pharmacodynamic data for
      fosfomycin are limited. METHODS: Sixty-four clinical isolates of P. aeruginosa
      (MDR and non-MDR) from two Australian hospitals were collected; 59 isolates were
      from patients with cystic fibrosis and 5 isolates were from critically ill
      patients. The in vitro pharmacodynamic properties of fosfomycin (disodium) were
      investigated via MICs (all isolates) and, for selected isolates, via time-kill
      kinetics (static and dynamic models; concentration range, 1-1024 mg/L),
      population analysis profiles (PAPs) and post-antibiotic effect (PAE). Two inocula
      (~10(6) and ~10(8) cfu/mL) were included in static time-kill studies to examine
      the effect of inocula on bacterial killing. RESULTS: MICs ranged from 1 to >512
      mg/L, with 61% of isolates considered fosfomycin susceptible (MIC <=64 mg/L). The
      MIC distributions for MDR and non-MDR isolates were similar. Baseline PAPs
      indicated heteroresistance in all isolates tested. Time-kill studies showed
      moderate (maximum killing ~3 log10 cfu/mL), time-dependent killing at the low
      inoculum with regrowth at 24 h. Most concentrations resulted in complete
      replacement of fosfomycin-susceptible colonies by fosfomycin-resistant colonies.
      Bacterial killing was virtually eliminated at the high inoculum. The PAE ranged
      from 0.3 to 5.5 h. CONCLUSIONS: These data suggest monotherapy with fosfomycin
      may be problematic for the treatment of infections caused by P. aeruginosa.
      Further investigation of fosfomycin combination therapy is warranted.

PMID- 26209312
TI  - Mortality burden related to infection with carbapenem-resistant Gram-negative
      bacteria among haematological cancer patients: a retrospective cohort study.
AB  - OBJECTIVES: Carbapenem-resistant Gram-negative bacteria (CRGNB) pose a clinical
      challenge. We attempted to estimate the mortality burden of CRGNB among
      haematological cancer patients. METHODS: This was a retrospective cohort study.
      We included adult patients hospitalized in the haemato-oncological/bone marrow
      transplantation departments for chemotherapy, between 2008 and 2014, with Gram
      negative aerobic bacteraemia. We compared patients with CRGNB and carbapenem
      susceptible Gram-negative bacteraemia (CSGNB). The primary outcome was 14 day all
      cause mortality. In addition, we assessed 1 year survival. Multivariable
      logistics regression analysis and adjusted Cox regression analysis were
      conducted. Analyses were adjusted to the propensity for CRGNB bacteraemia.
      RESULTS: The cohort included mostly young patients (mean age 50.1 years) with
      acute leukaemia (264/423, 62.4%) and the median absolute neutrophil count at
      bacteraemia onset was 0 * 10(9)/L. The unadjusted 14 day mortality rate was
      higher for patients with CRGNB compared with CSGNB [45.6% (47/103) versus 15%
      (48/320), respectively (P < 0.001)]. Adjusting to baseline prognostic factors,
      infection characteristics and the propensity score retained a significant
      association between CRGNB and 14 day mortality (OR 5.14, 95% CI 2.32-11.38).
      Including only the first bacteraemic episode per patient, 1 year mortality was
      74.7% (68/91) for patients with CRGNB versus 49.8% (119/239) for patients with
      CSGNB (P < 0.001). Adjusting for risk factors associated with 1 year mortality,
      the HR for mortality with CRGNB was 1.48 (95% CI 1-2.2). CRGNB bacteraemia was
      associated with several risk factors for mortality, including inappropriate
      empirical antibiotic treatment and less effective definitive antibiotics.
      CONCLUSIONS: This study demonstrated a significant adjusted association between
      CRGNB and mortality up to 1 year among haemato-oncological patients receiving
      chemotherapy.

PMID- 26209313
TI  - Sequencing of plasmids pAMBL1 and pAMBL2 from Pseudomonas aeruginosa reveals a
      blaVIM-1 amplification causing high-level carbapenem resistance.
AB  - BACKGROUND: Carbapenemases are a major concern for the treatment of infectious
      diseases caused by Gram-negative bacteria. Although plasmids are responsible for
      the spread of resistance genes among these pathogens, there is limited
      information on the nature of the mobile genetic elements carrying carbapenemases
      in Pseudomonas aeruginosa. METHODS: We combined data from two different next
      generation sequencing platforms, Illumina HiSeq2000 and PacBio RSII, to obtain
      the complete nucleotide sequences of two blaVIM-1-carrying plasmids (pAMBL1 and
      pAMBL2) isolated from P. aeruginosa clinical isolates. RESULTS: Plasmid pAMBL1
      has 26 440 bp and carries a RepA_C family replication protein. pAMBL1 is similar
      to plasmids pNOR-2000 and pKLC102 from P. aeruginosa and pAX22 from Achromobacter
      xylosoxidans, which also carry VIM-type carbapenemases. pAMBL2 is a 24 133 bp
      plasmid with a replication protein that belongs to the Rep_3 family. It shows a
      high degree of homology with a fragment of the blaVIM-1-bearing plasmid pPC9 from
      Pseudomonas putida. Plasmid pAMBL2 carries three copies of the blaVIM-1 cassette
      in an In70 class 1 integron conferring, unlike pAMBL1, high-level resistance to
      carbapenems. CONCLUSIONS: We present two new plasmids coding for VIM-1
      carbapenemase from P. aeruginosa and report that the presence of three copies of
      blaVIM-1 in pAMBL2 produces high-level resistance to carbapenems.

PMID- 26209314
TI  - Clinical correlates of raphe serotonergic dysfunction in early Parkinson's
      disease.
AB  - Post-mortem and neuroimaging studies suggest that the serotonergic system, which
      originates from the brainstem raphe nuclei, is disrupted in Parkinson's disease.
      This could contribute to the occurrence of non-motor symptoms and tremor, which
      are only partially explained by dopamine loss. However, the level of involvement
      of the serotonergic raphe nuclei in early Parkinson's disease is still debated.
      (123)I-FP-CIT single photon emission computed tomography is a marker of dopamine
      and serotonin transporter availability. While (123)I-FP-CIT binds primarily to
      dopamine transporters in the striatum, its binding in the brainstem raphe nuclei
      reflects serotonin transporter availability. We interrogated baseline single
      photon emission computed tomography scans of subjects recruited by the
      Parkinson's Progression Markers Initiative to determine: (i) the integrity of the
      brainstem raphe nuclei in early Parkinson's disease; and (ii) whether raphe
      serotonin transporter levels correlate with severity of tremor and symptoms of
      fatigue, depression, and sleep disturbance. Three hundred and forty-five patients
      with early drug-naive Parkinson's disease, 185 healthy controls, and 56 subjects
      with possible Parkinson's disease without evidence of dopaminergic deficit were
      included. In the Parkinson's disease cohort, 37 patients had a tremulous, 106
      patients had a pure akinetic-rigid, and 202 had a mixed phenotype. Patients with
      Parkinson's disease had significantly lower serotonin transporter availability in
      the brainstem raphe nuclei compared to controls (P < 0.01) and subjects without
      evidence of dopaminergic deficit (P < 0.05). However, only 13% of patients with
      Parkinson's disease individually had reduced signals. Raphe serotonin transporter
      availability over the entire Parkinson's disease cohort were associated with rest
      tremor amplitude (beta = -0.106, P < 0.05), rest tremor constancy (beta = -0.109,
      P < 0.05), and index of rest tremor severity (beta = -0.104, P < 0.05). The
      tremulous Parkinson's disease subgroup had significantly lower raphe serotonin
      transporter availability but less severe striatal dopaminergic deficits compared
      to akinetic-rigid patients with no resting tremor (P < 0.05). In tremulous
      patients, raphe serotonin transporter availability was also associated with rest
      tremor constancy (beta = -0.380, P < 0.05) and index of rest tremor severity
      (beta = -0.322, P < 0.05). There was no association between raphe serotonin
      transporter availability and fatigue, depression, excessive daytime sleepiness,
      or rapid eye movement sleep behaviour disorder in early Parkinson's disease. We
      conclude that the raphe nuclei are affected in a subgroup of early drug-naive
      Parkinson's disease patients and that reduced raphe serotonin transporter
      availability is associated with the severity of resting tremor but not non-motor
      symptoms. 

PMID- 26209315
TI  - Mitochondrial DNA copy number differentiates the Leber's hereditary optic
      neuropathy affected individuals from the unaffected mutation carriers.

PMID- 26209316
TI  - Reply: Mitochondrial DNA copy number differentiates the Leber's hereditary optic
      neuropathy affected individuals from the unaffected mutation carriers.

PMID- 26209317
TI  - Antioxidant activity and hepatoprotective potential of Cedrelopsis grevei on
      cypermethrin induced oxidative stress and liver damage in male mice.
AB  - BACKGROUND: The liver is the most sensitive and main target organ of pesticide
      toxicity and damage, they play an essential role in metabolism and detoxification
      of pesticides. Due to these functions, hepatotoxicity continues to be among the
      main threats to public health, and they remain problems throughout the world.
      Therefore, the present study was designed to evaluate the antioxidant and
      hepatoprotective effects of Cedrelopsis grevei leaves against cypermethrin (Cyp)
      induced oxidative stress and liver damage in male mice. METHODS: The extracts
      were subjected to different analyses (phenolics, tannin, flavonoids, antioxidant
      activity and reducing power assays). For hepatoprotective evaluation, male mice
      were daily exposed to Cyp and/or C. grevei by gavages for 28 days.
      Hepatoprotective effects were demonstrated by significant alterations in serum
      liver dysfunction biomarker enzymes, liver lipid peroxidation and antioxidant
      enzymes. RESULTS: The antioxidant activity of C. grevei methanolic extract was
      the highest with an IC50<225 MUg/ml by DPPH assay. The high dose of methanolic
      extract (300 mg/kg. b.wt.) was effective to attenuate the perturbations in the
      tested enzymes. Histopathological examination in the liver tissue of those mice,
      demonstrated that a co-administration of methanolic extract (150 & 300 mg/kg/day)
      showed marked improvement in its histological structure in comparison to Cyp
      treated group alone and represented by nil to moderate degree in inflammatory
      cells. CONCLUSIONS: In view of the data of the present study, it can deduce that
      cypermethrin caused oxidative damage and liver dysfunction in male mice. C.
      grevei extract has protective effects on cypermethrin-induced lipid peroxidation,
      oxidative stress and liver damage. Results indicated that administration of C.
      grevei is useful, easy, and economical to protect humans against pesticide
      toxicity. The results presented here can be considered as the first information
      on the hepatoprotective and antioxidant properties of C. grevei extracts. In a
      future study, we will identify and investigate the components responsible for the
      hepatoprotective and antioxidant activities of C. grevei.

PMID- 26209318
TI  - Occupational health of home care aides: results of the safe home care survey.
AB  - OBJECTIVES: In countries with ageing populations, home care (HC) aides are among
      the fastest growing jobs. There are few quantitative studies of HC occupational
      safety and health (OSH) conditions. The objectives of this study were to: (1)
      assess quantitatively the OSH hazards and benefits for a wide range of HC working
      conditions, and (2) compare OSH experiences of HC aides who are employed via
      different medical and social services systems in Massachusetts, USA. METHODS: HC
      aides were recruited for a survey via agencies that employ aides and schedule
      their visits with clients, and through a labour union of aides employed directly
      by clients or their families. The questionnaire included detailed questions about
      the most recent HC visits, as well as about individual aides' OSH experiences.
      RESULTS: The study population included 1249 HC aides (634 agency-employed, 615
      client-employed) contributing information on 3484 HC visits. Hazards occurring
      most frequently related to musculoskeletal strain, exposure to potentially
      infectious agents and cleaning chemicals for infection prevention and experience
      of violence. Client-hired and agency-hired aides had similar OSH experiences with
      a few exceptions, including use of sharps and experience of verbal violence.
      CONCLUSIONS: The OSH experience of HC aides is similar to that of aides in
      institutional healthcare settings. Despite OSH challenges, HC aides enjoy caring
      for others and the benefits of HC work should be enhanced. Quantification of HC
      hazards and benefits is useful to prioritise resources for the development of
      preventive interventions and to provide an evidence base for policy-setting.

PMID- 26209319
TI  - Development of patent Litomosoides sigmodontis infections in semi-susceptible
      C57BL/6 mice in the absence of adaptive immune responses.
AB  - BACKGROUND: One of the most advantageous research aspects of the murine model of
      filariasis, Litomosoides sigmodontis, is the availability of mouse strains with
      varying susceptibility to the nematode infection. In C57BL/6 mice, L. sigmodontis
      worms are largely eliminated in this strain by day 40 post-infection and never
      produce their offspring, microfilariae (Mf). This provides a unique opportunity
      to decipher potential immune pathways that are required by filariae to achieve a
      successful infection. In this study we tracked worm development and patency, the
      production of microfilariae and thus the transmission life-stage, in Rag2IL
      2Rgamma(-/-) mice which are deficient in T, B and NK cell populations. FINDINGS:
      Although worm burden was comparable between wildtype (WT) and Rag2IL-2Rgamma(-/-)
      mice on d30, by day 72 post-infection, parasites in Rag2IL-2Rgamma(-/-) mice were
      still in abundance, freely motile and all mice presented high quantities of Mf
      both at the site of infection, the thoracic cavity (TC), and in peripheral blood.
      Levels of cytokine (IL-4, IL-6, TNFalpha) and chemokine (MIP-2, RANTES, Eotaxin)
      parameters were generally low in the TC of infected Rag2IL-2Rgamma(-/-)mice at
      both time-points. The frequency of neutrophils however was higher in Rag2IL
      2Rgamma(-/-)mice whereas eosinophils and macrophage populations, including
      alternatively activated macrophages, were elevated in WT controls. CONCLUSION:
      Our data highlight that adaptive immune responses prevent the development of
      patent L. sigmodontis infections in semi-susceptible C57BL/6 mice and suggest
      that induction of such responses may offer a strategy to prevent transmission of
      human filariasis.

PMID- 26209320
TI  - Personality disorders and the DSM-5: Scientific and extra-scientific factors in
      the maintenance of the status quo.
AB  - OBJECTIVE: The aim of this study was to review and discuss the evidence for
      dimensional classification of personality disorders and the historical and
      sociological bases of psychiatric nosology and research. METHOD: Categorical and
      dimensional conceptualisations of personality disorder are reviewed, with a focus
      on the Diagnostic and Statistical Manual of Mental Disorders-system's
      categorisation and the Five-Factor Model of personality. This frames the events
      leading up to the Diagnostic and Statistical Manual of Mental Disorders, 5th
      Edition, personality disorder debacle, where the implementation of a hybrid model
      was blocked in a last-minute intervention by the American Psychiatric Association
      Board of Trustees. Explanations for these events are discussed, including the
      existence of invisible colleges of researchers and the fear of risking a
      'scientific revolution' in psychiatry. RESULTS: A failure to recognise extra
      scientific factors at work in classification of mental illness can have a
      profound and long-lasting influence on psychiatric nosology. In the end it was
      not scientific factors that led to the failure of the hybrid model of personality
      disorders, but opposing forces within the mental health community in general and
      the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Task
      Force in particular. CONCLUSION: Substantial evidence has accrued over the past
      decades in support of a dimensional model of personality disorders. The events
      surrounding the Diagnostic and Statistical Manual of Mental Disorders, 5th
      Edition, Personality and Personality Disorders Work Group show the difficulties
      in reconciling two different worldviews with a hybrid model. They also indicate
      the future of a psychiatric nosology that will be increasingly concerned with
      dimensional classification of mental illness. As such, the road is paved for more
      substantial changes to personality disorder classification in the International
      Classification of Diseases, 11th Revision, in 2017.

PMID- 26209321
TI  - Resolution of a manic episode treated with activated charcoal: Evidence for a
      brain-gut axis in bipolar disorder.

PMID- 26209322
TI  - The Neuropsychiatric Effects of CNS Structural Abnormalities (NECSA)
      classification: An aid to differential diagnosis.

PMID- 26209323
TI  - Capacity in mental health law: We are heading in the right direction.

PMID- 26209324
TI  - Suicide prevention: The role of the psychiatrist.

PMID- 26209325
TI  - Common familial risk factors for schizophrenia and diabetes mellitus.
AB  - OBJECTIVE: The co-occurrence of type 2 diabetes and psychosis is an important
      form of medical comorbidity within individuals, but no large-scale study has
      evaluated comorbidity within families. The aim of this study was to determine
      whether there is evidence for familial comorbidity between type 2 diabetes and
      psychosis. METHOD: Data were analysed from an observational study of a nationally
      representative sample of 1642 people with psychosis who were in contact with
      psychiatric services at the time of survey (The 2010 Australian National Survey
      of Psychosis). Participants were aged 18-64 years and met World Health
      Organization's International Classification of Diseases, 10th Revision diagnostic
      criteria for a psychotic disorder (857 with schizophrenia, 319 with bipolar
      disorder with psychotic features, 293 with schizoaffective disorder, 81 with
      depressive psychosis and 92 with delusional disorder or other non-organic
      psychoses). Logistic regression was used to estimate the association between a
      family history of diabetes and a family history of schizophrenia. RESULTS: A
      positive family history of diabetes was associated with a positive family history
      of schizophrenia in those with a psychotic disorder (odds ratio = 1.35, p = 0.01,
      adjusted for age and gender). The association was different in those with an
      affective versus non-affective psychosis (odds ratio = 0.613, p = 0.019, adjusted
      for age and gender) and was significant only in those with a non-affective
      psychosis, specifically schizophrenia (odds ratio = 1.58, p = 0.005, adjusted for
      age and sex). Adjustment for demographic factors in those with schizophrenia
      slightly strengthened the association (odds ratio = 1.74, p = 0.001, adjusted for
      age, gender, diagnosis, ethnicity, education, employment, income and marital
      status). CONCLUSION: Elevated risk for type 2 diabetes in people with
      schizophrenia is not simply a consequence of antipsychotic medication; type 2
      diabetes and schizophrenia share familial risk factors.

PMID- 26209326
TI  - Capacity in mental health law: Are we heading in the right direction?

PMID- 26209327
TI  - CD147 expression predicts biochemical recurrence after prostatectomy independent
      of histologic and pathologic features.
AB  - BACKGROUND: CD147 is an MMP-inducing protein often implicated in cancer
      progression. The purpose of this study was to investigate the expression of CD147
      in prostate cancer (PCa) progression and the prognostic ability of CD147 in
      predicting biochemical recurrence after prostatectomy. METHODS: Plasma membrane
      localized CD147 protein expression was quantified in patient samples using
      immunohistochemistry and multispectral imaging, and expression was compared to
      clinico-pathological features (pathologic stage, Gleason score, tumor volume,
      preoperative PSA, lymph node status, surgical margins, biochemical recurrence
      status). CD147 specificity and expression were confirmed with immunoblotting of
      prostate cell lines, and CD147 mRNA expression was evaluated in public expression
      microarray datasets of patient prostate tumors. RESULTS: Expression of CD147
      protein was significantly decreased in localized tumors (pT2; p = 0.02) and
      aggressive PCa (>=pT3; p = 0.004), and metastases (p = 0.001) compared to benign
      prostatic tissue. Decreased CD147 was associated with advanced pathologic stage
      (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted
      biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of
      clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa,
      representing non-glycosylated and glycosylated forms of CD147 protein, and CD147
      expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p
      = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason
      score and pathologic stage in patient tumors but is not associated with
      recurrence status. CONCLUSIONS: Membrane-associated CD147 expression is
      significantly decreased in PCa compared to non-malignant prostate tissue and is
      associated with tumor progression, and low CD147 expression predicts biochemical
      recurrence after prostatectomy independent of pathologic stage, Gleason score,
      lymph node status, surgical margins, and tumor volume in multivariable analysis.

PMID- 26209328
TI  - Impact of obstructive sleep apnea on lung volumes and mechanical properties of
      the respiratory system in overweight and obese individuals.
AB  - BACKGROUND: Even through narrowing of the upper-airway plays an important role in
      the generation of obstructive sleep apnea (OSA), the peripheral airways is
      implicated in pre-obese and obese OSA patients, as a result of decreased lung
      volume and increased lung elastic recoil pressure, which, in turn, may aggravate
      upper-airway collapsibility. METHODS: A total of 263 male (n = 193) and female (n
      = 70) subjects who were obese to various degrees without a history of lung
      diseases and an expiratory flow limitation, but troubled with snoring or
      suspicion of OSA were included in this cross-sectional study. According to
      nocturnal-polysomnography the subjects were distributed into OSA and non-OSA
      groups, and were further sub-grouped by gender because of differences between
      males and females, in term of, lung volume size, airway resistance, and the
      prevalence of OSA among genders. Lung volume and respiratory mechanical
      properties at different-frequencies were evaluated by plethysmograph and an
      impulse oscillation system, respectively. RESULTS: Functional residual capacity
      (FRC) and expiratory reserve volume were significantly decreased in the OSA group
      compared to the non-OSA group among males and females. As weight and BMI in males
      in the OSA group were greater than in the non-OSA group (90 +/- 14.8 kg vs. 82 +/
      10.4 kg, p < 0.001; 30.5 +/- 4.2 kg/m(2) vs. 28.0 +/- 3.0 kg/m(2), p < 0.001),
      multiple regression analysis was required to adjust for BMI or weight and
      demonstrated that these lung volumes decreases were independent from BMI and
      associated with the severity of OSA. This result was further confirmed by the
      female cohort. Significant increases in total respiratory resistance and
      decreases in respiratory conductance (Grs) were observed with increasing severity
      of OSA, as defined by the apnea-hypopnea index (AHI) in both genders. The
      specific Grs (sGrs) stayed relatively constant between the two groups in woman,
      and there was only a weak association between AHI and sGrs among man. Multiple
      stepwise-regression showed that reactance at 5 Hz was highly correlated with AHI
      in males and females or hypopnea index in females, independently-highly
      correlated with peripheral-airway resistance and significantly associated with
      decreasing FRC. CONCLUSIONS: Total respiratory resistance and peripheral airway
      resistance significantly increase, and its inverse Grs decrease, in obese
      patients with OSA in comparison with those without OSA, and are independently
      associated with OSA severity. These results might be attributed to the abnormally
      increased lung elasticity recoil pressure on exhalation, due to increase in lung
      elasticity and decreased lung volume in obese OSA.

PMID- 26209329
TI  - Sortin2 enhances endocytic trafficking towards the vacuole in Saccharomyces
      cerevisiae.
AB  - BACKGROUND: A highly regulated trafficking of cargo vesicles in eukaryotes
      performs protein delivery to a variety of cellular compartments of endomembrane
      system. The two main routes, the secretory and the endocytic pathways have
      pivotal functions in uni- and multi-cellular organisms. Protein delivery and
      targeting includes cargo recognition, vesicle formation and fusion. Developing
      new tools to modulate protein trafficking allows better understanding the
      endomembrane system mechanisms and their regulation. The compound Sortin2 has
      been described as a protein trafficking modulator affecting targeting of the
      vacuolar protein carboxypeptidase Y (CPY), triggering its secretion in
      Saccharomyces cerevisiae. RESULTS: A reverse chemical-genetics approach was used
      to identify key proteins for Sortin2 bioactivity. A genome-wide Sortin2
      resistance screen revealed six yeast deletion mutants that do not secrete CPY
      when grown at Sortin2 condition where the parental strain does: met18, sla1,
      clc1, dfg10, dpl1 and yjl175w. Integrating mutant phenotype and gene ontology
      annotation of the corresponding genes and their interactome pointed towards a
      high representation of genes involved in the endocytic process. In wild type
      yeast endocytosis towards the vacuole was faster in presence of Sortin2, which
      further validates the data of the genome-wide screen. This effect of Sortin2
      depends on structural features of the molecule, suggesting compound specificity.
      Sortin2 did not affect endocytic trafficking in Sortin2-resistant mutants,
      strongly suggesting that the Sortin2 effects on the secretory and endocytic
      pathways are linked. CONCLUSIONS: Overall, the results reveal that Sortin2
      enhances the endocytic transport pathway in Saccharomyces cerevisiae. This
      cellular effect is most likely at the level where secretory and endocytic
      pathways are merged. Them Sortin2 specificity over the endomembrane system places
      it as a powerful biological modulator for cell biology.

PMID- 26209331
TI  - Strategies for the prevention and management of methotrexate-related nausea and
      vomiting in juvenile idiopathic arthritis: results of a UK Paediatric
      Rheumatology prescriber survey.

PMID- 26209330
TI  - Treating rheumatological diseases and co-morbidities with interleukin-1 blocking
      therapies.
AB  - The inflammatory cytokines IL-1alpha and IL-1beta orchestrate local and systemic
      inflammatory responses underlying a broad spectrum of diseases. Three agents for
      reducing IL-1 activities are currently available. Anakinra is a recombinant form
      of the naturally occurring IL-1 receptor antagonist. Anakinra binds to the IL-1
      receptor and prevents the activity of IL-1alpha and IL-1beta. The soluble decoy
      receptor rilonacept and the neutralizing mAb canakinumab block IL-1beta. A mAb
      directed against the IL-1 receptor and a neutralizing anti-human IL-1alpha are in
      clinical trials. The availability of therapies specifically targeting IL-1
      unveiled the pathological role of IL-1-mediated inflammation in a broadening list
      of diseases. Conditions effectively treated with agents blocking IL-1 range from
      classic rheumatic diseases, such as RA and gout, to autoinflammatory syndromes,
      such as systemic JIA and FMF. However, IL-1 antagonism is also effective against
      highly prevalent inflammatory diseases, namely cardiovascular diseases and type 2
      diabetes, conditions that are frequently encountered as co-morbidities in
      patients with rheumatic diseases. Thereby, IL-1 inhibition has the potential to
      lift the burden of disease for patients with rheumatic conditions, but also to
      provide clinical benefits beyond the efficacy on osteoarticular manifestations.

PMID- 26209332
TI  - Impact of cytokine release on ventricular function after hepatic reperfusion: a
      prospective observational echocardiographic study with tissue Doppler imaging.
AB  - BACKGROUND: Postreperfusion syndrome and haemodynamic instability are predictors
      for poor outcome after liver transplantation. Cytokine release has been claimed
      to be responsible for postreperfusion syndrome. However, the underlying
      pathophysiologic mechanism is not clarified. The aim of this prospective
      observational study was to correlate cardiac performance (measured by
      transoesophageal echocardiography (TEE), Doppler and Tissue Doppler Imaging
      (TDI)) to plasmatic cytokines: IL-6, IL-8, CXCL1, TGF-beta and CD40L at 5
      different time points during liver transplantation. METHODS: Seventeen
      consecutive patients scheduled for orthotopic liver transplantation, age 18 to 75
      years without contraindication for transoesophageal echocardiography were
      included. Patients were monitored with TEE and TDI. Systolic and diastolic
      cardiac function, MAP, MPAP, CVP, PCWP, CO and blood samples for cytokine assays
      were recorded or collected after induction, 15 min after vena cava inferior
      clamping, 2 to 5 min after reperfusion, 60 min after reperfusion and at the end
      of surgery. RESULTS: Mean arterial pressure and catecholamine requirements
      remained unchanged, MPAP, CVP and CO increased, SVR decreased after unclamping.
      Postreperfusion syndrome did not develop. The haemodynamic parameters and the
      variations of TEE parameters were consistent with the volume load changes during
      clamping and declamping and did not reveal systolic or diastolic cardiac
      dysfunction. All cytokines, except TGF-beta, increased. CONCLUSION: These
      findings suggest, that significant cytokine release during liver transplantation
      is not necessarily coincident with haemodynamic instability and impaired cardiac
      function. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00547924.

PMID- 26209333
TI  - Cardiac MRI in a young man with suspected arrhythmogenic right ventricular
      cardiomyopathy (ARVC).

PMID- 26209334
TI  - Outcomes with prolonged clopidogrel therapy after coronary stenting in patients
      with chronic kidney disease.
AB  - OBJECTIVES: Patients with chronic kidney disease (CKD) are at high risk of death
      or myocardial infarction (MI) after percutaneous coronary interventions (PCI). We
      assessed whether prolonged dual antiplatelet therapy beyond the recommended 12
      months may prevent adverse outcomes in patients with CKD receiving drug-eluting
      stents (DES) or bare-metal stents (BMS). METHODS: We studied all Veterans
      receiving PCI with BMS or first-generation DES in the Veterans Affairs (VA)
      Healthcare System between 2002 and 2006, classified by CKD (estimated glomerular
      filtration rate <60 mL/min) or normal renal function. We used landmark analyses
      from 12 months after PCI with Cox proportional hazards multivariable and
      propensity-adjusted models to assess the effect of prolonged clopidogrel (more
      than 12  months) versus 12 months or less after PCI on clinical outcomes from 1
      year to 4 years after PCI. RESULTS: Of 23 042 eligible subjects receiving PCI,
      4880 (21%) had CKD. Compared with normal renal function, patients with CKD had
      higher risks of death or MI 1-4 years after DES (21% vs 12%, HR=1.75; 95% CI 1.51
      to 2.04) or BMS (28% vs 15%, HR=2.10; 95% CI 1.90 to 2.32). In patients with CKD
      receiving DES, clopidogrel use of more than 12 months after PCI was associated
      with lower risks of death or MI (18% vs 24%, HR=0.74; 95% CI 0.58 to 0.95), and
      death (15% vs 23%, HR=0.61; 95% CI 0.47 to 0.80), but had no effect on repeat
      revascularisation 1-4 years after PCI. CONCLUSIONS: In patients with CKD,
      prolonging clopidogrel beyond 12 months after PCI may decrease the risk of death
      or MI only in patients receiving first-generation DES. These results support a
      patient-tailored approach to prolonging clopidogrel after PCI.

PMID- 26209335
TI  - Ectopic cerebellar tissue of the posterior cranial fossa: diffusion tensor
      tractography and MR spectroscopy findings.
AB  - PURPOSE: Well-differentiated ectopic cerebellar tissue is extremely rare, with
      only 12 cases in the literature. Here, we describe a unique case of
      radiologically proven ectopic cerebellar tissue, using diffusion tensor
      tractography (DTT) and MR spectroscopy (MRS) findings, in a 6-day-old newborn.
      CASE: A 6-day-old newborn who had previously a fetal MRI referred to our
      department with the suspicion of an arachnoid cyst of the posterior fossa.
      Including the central nervous system, all of his physical examination tests were
      normal. Postnatal transcranial ultrasound (US) imaging and brain MRI also
      revealed a large posterior fossa cyst and a solid mass nearby the cerebellar
      tissue. The tissue showed a small connection and isointense signal with the
      cerebellum. Upon DTT, both the cerebellum and nearby solid tissue represented the
      same FA values. Tractographic studies showed a connection with fibers extending
      along the left cerebellar hemisphere from this tissue. The single voxel MRS of
      this solid tissue also revealed high choline (Cho) and a smaller N
      acetylaspartate (NAA) concentration similar to that of the normal newborn
      cerebellum. CONCLUSION: Ectopic cerebellar tissue can be characterized by
      advanced neuroimaging tools, like DTT and MRS, which provide information about
      brain metabolite concentrations and the microstructural integrity. In this way,
      unnecessary surgery can be avoided in order to obtain a histopathological
      diagnosis.

PMID- 26209336
TI  - The use of a process challenge device in dental office gravity displacement
      tabletop sterilizers.
AB  - There is evidence that dental office sterilizers often fail to pass the challenge
      of a biological indicator test. The use of a class 5 integrating indicator in
      each load could reduce the risk of instruments being released when all parameters
      for sterilization have not been met. 

PMID- 26209337
TI  - Health Care-Associated Infections Studies Project Case #2: a 2015 American
      Journal of Infection Control and National Healthcare Safety Network data quality
      collaboration.

PMID- 26209338
TI  - Health Care-Associated Infections Studies Project Case #1: A 2015 American
      Journal of Infection Control and National Healthcare Safety Network data quality
      collaboration.

PMID- 26209339
TI  - Accuracy evaluation of CAD/CAM generated splints in orthognathic surgery: a
      cadaveric study.
AB  - INTRODUCTION: To evaluate the accuracy of CAD/CAM generated splints in
      orthognathic surgery by comparing planned versus actual post-operative 3D images.
      METHODS: Specific planning software (SimPlant((r)) OMS Standalone 14.0) was used
      to perform a 3D virtual Le Fort I osteotomy in 10 fresh human cadaver heads.
      Stereolithographic splints were then generated and used during the surgical
      procedure to reposition the maxilla according to the planned position. Pre
      operative planned and postoperative 3D CT scan images were fused and imported to
      dedicated software (MATLAB((r))) 7.11.) for calculating the translational and
      rotational (pitch, roll and yaw) differences between the two 3D images.
      Geometrical accuracy was estimated using the Root Mean Square Deviations (RMSD)
      and lower and upper limits of accuracy were computed using the Bland & Altman
      method, with 95 % confidence intervals around the limits. The accuracy cutoff was
      set at +/- 2 mm for translational and <= 4 degrees  for rotational measurements.
      RESULTS: Overall accuracy between the two 3D images was within the accuracy
      cutoff for all values except for the antero-posterior positioning of the maxilla
      (2.17 mm). The translational and rotational differences due to the splint were
      all within the accuracy cutoff. However, the width of the limits of agreement
      (range between lower and upper limits) showed that rotational differences could
      be particularly large. CONCLUSION: This study demonstrated that maxillary
      repositioning can be accurately approximated and thus predicted by specific
      computational planning and CAD/CAM generated splints in orthognathic surgery.
      Further study should focus on the risk factors for inaccurate prediction.

PMID- 26209340
TI  - Macrolide-lincosamide-streptogramin resistance phenotypes and genotypes of
      coagulase-positive Staphylococcus aureus and coagulase-negative staphylococcal
      isolates from bovine mastitis.
AB  - BACKGROUND: There are limited data available on macrolide-lincosamide
      streptogramin (MLS) resistance of Staphylococcus aureus (S. aureus) and coagulase
      negative staphylococci (CoNS) from bovine milk in China. To address this
      knowledge gap, MLS resistance was determined in 121 S. aureus and 97 CoNS
      isolates. Minimum inhibitory concentrations (MICs) of MLS antibiotics were
      determined by an agar dilution method, while differentiation of MLS phenotypes
      was performed by a double-disc diffusion test. MLS resistance genotypes were
      determined by PCR for corresponding resistance genes. RESULTS: Forty (33.1%) S.
      aureus and 65 (67.0%) CoNS were resistant to erythromycin, whereas all 218
      isolates were susceptible to quinupristin/dalfopristin. Among 40 erythromycin
      resistant (ER-R) S. aureus and 65 ER-R CoNS isolates, 38 S. aureus and 40 CoNS
      isolates exhibited the inducible MLS (iMLS) resistance phenotype and 2 S. aureus
      and 20 CoNS isolates expressed the constitutive MLS resistance (cMLS) phenotype.
      At the same time, 5 CoNS isolates exhibited resistance to erythromycin but
      susceptibility to clindamycin (the MS phenotype). An inactivating enzyme gene
      lnu(A), methylase genes erm(C) and erm(B), efflux genes msr(A)/msr(B), a
      phosphotransferase gene mph(C), an esterase gene ere(A) and the streptogramin
      resistance determinant vga(A) were detected individually or in combinations.
      Among them, genes lnu(A), erm(C) and mph(C) predominated. The ereA gene was
      detected for the first time in staphylococci of bovine milk origin. Resistance
      genes also existed in erythromycin-susceptible isolates. CONCLUSIONS: Our study
      demonstrated a high level of resistance to MLS antibiotics in staphylococci from
      bovine mastitic milk, especially with a high rate of the iMLS phenotype in S.
      aureus isolates. These data suggest that MLS antibiotics should be used
      judiciously to treat or prevent bovine mastitis caused by staphylococci.

PMID- 26209341
TI  - Water reduction by constructed wetlands treating waste landfill leachate in a
      tropical region.
AB  - One of the key challenges in landfill leachate management is the prevention of
      environmental pollution by the overflow of untreated leachate. To evaluate the
      feasibility of constructed wetlands (CWs) for the treatment of waste landfill
      leachate in tropical regions, water reduction and pollutant removal by a CW
      subjected to different flow patterns (i.e., horizontal subsurface flow (HSSF) and
      free water surface (FWS)) were examined in both rainy and dry seasons in
      Thailand. A pilot-scale CW planted with cattail was installed at a landfill site
      in Thailand. With HSSF, the CW substantially removed pollutants from the landfill
      leachate without the need to harvest plants, whereas with FWS, it only slightly
      removed pollutants. Under both flow patterns, the CW significantly reduced the
      leachate volume to a greater extent than surface evaporation, which is regarded
      as an effect of the storage pond. Additionally, water reduction occurred
      regardless of season and precipitation, within the range 0-9 mm d(-1). In the
      case of low feeding frequency, water reduction by the CW with HSSF was lower than
      that with FWS. However, high feeding frequency improved water reduction by the CW
      with HSSF and resulted in a similar reduction to that observed with FWS, which
      exhibited maximum evapotranspiration. In terms of water reduction, with both HSSF
      in conjunction with high frequency feeding and FWS, the CW provided a high degree
      of evapotranspiration. However, pollutant removal efficiencies with HSSF were
      higher than for FWS. The present study suggested that CWs with HSSF and high
      frequency feeding could be useful for the prevention of uncontrollable dispersion
      of polluted leachate in the tropical climate zone.

PMID- 26209342
TI  - Potential SRF generation from a closed landfill in northern Italy.
AB  - The aim of this work is to assess the possibility of producing solid recovered
      fuel (SRF) and "combustible SRF" from a landfill located in the north of Italy,
      where the waste is placed in cylindrical wrapped bales. Since the use of
      landfills for the disposal of municipal solid waste has many technical
      limitations and is subject to strict regulations and given that landfill post
      closure care is very expensive, an interesting solution is to recover the bales
      that are stored in the landfill. The contents of the bales can then be used for
      energy recovery after specific treatments. Currently the landfill is closed and
      the local municipal council together with an environmental agency are considering
      constructing a mechanical biological treatment (MBT) plant for SRF production.
      The municipal solid waste that is stored in the landfill, the bio-dried material
      produced by the hypothetically treated waste in a plant for bio-drying, and the
      SRF obtained after the post-extraction of inert materials, metals and glass from
      the bio-dried material were characterized according to the quality and
      classification criteria of regulations in Italy. The analysis highlighted the
      need to treat the excavated waste in a bio-drying plant and later to remove the
      inert waste, metals and glass. Thus in compliance with Italian law, the material
      has a high enough LHV to be considered as "combustible SRF", (i.e. an SRF with
      enhanced characteristics). 

PMID- 26209343
TI  - Thermal and mechanical stabilization process of the organic fraction of the
      municipal solid waste.
AB  - In the present study a thermo-mechanical treatment for the disposal of the
      Organic Fraction of Municipal Solid Waste (OFMSW) at apartment or condominium
      scale is proposed. The process presents several advantages allowing to perform a
      significant volume and moisture reduction of the produced waste at domestic scale
      thus producing a material with an increased storability and improved
      characteristics (e.g. calorific value) that make it available for further
      alternative uses. The assessment of the applicability of the proposed waste
      pretreatment in a new scheme of waste management system requires several research
      steps involving different competences and application scales. In this context, a
      preliminary study is needed targeting to the evaluation and minimization of the
      energy consumption associated to the process. To this aim, in the present paper,
      two configurations of a domestic appliance prototype have been presented and the
      effect of some operating variables has been investigated in order to select the
      proper configuration and the best set of operating conditions capable to minimize
      the duration and the energy consumption of the process. The performances of the
      prototype have been also tested on three model mixtures representing a possible
      daily domestic waste and compared with an existing commercially available
      appliance. The results obtained show that a daily application of the process is
      feasible given the short treatment time required and the energy consumption
      comparable to the one of the common domestic appliances. Finally, the evaluation
      of the energy recovered in the final product per unit weight of raw material
      shows that in most cases it is comparable to the energy required from the
      treatment. 

PMID- 26209344
TI  - Modelling informally collected quantities of bulky waste and reusable items in
      Austria.
AB  - Disparities in earnings between Western and Eastern European countries are the
      reason for a well-established informal sector actively involved in collection and
      transboundary shipment activities from Austria to Hungary. The preferred objects
      are reusable items and wastes within the categories bulky waste, WEEE and metals,
      intended to be sold on flea markets. Despite leading to a loss of recyclable
      resources for Austrian waste management, these informal activities may contribute
      to the extension of the lifetime of certain goods when they are reused in
      Hungary; nevertheless they are discussed rather controversially. The aim of this
      paper is to provide objective data on the quantities informally collected and
      transhipped. The unique activities of informal collectors required the
      development and implementation of a new set of methodologies. The concept of
      triangulation was used to verify results obtained by field visits, interviews and
      a traffic counting campaign. Both approaches lead to an estimation of approx.
      100,000 t per year of reusable items informally collected in Austria. This means
      that in addition to the approx. 72 kg/cap/yr formally collected bulky waste,
      bulky waste wood, household scrap (excluding packaging) and WEEE, up to a further
      12 kg/cap/yr might, in the case that informal collection is abandoned, end up as
      waste or in the second-hand sector.

PMID- 26209345
TI  - Fractionation and fluxes of metals and radionuclides during the recycling process
      of phosphogypsum wastes applied to mineral CO2 sequestration.
AB  - The industry of phosphoric acid produces a calcium-rich by-product known as
      phosphogypsum, which is usually stored in large stacks of millions of tons. Up to
      now, no commercial application has been widely implemented for its reuse because
      of the significant presence of potentially toxic contaminants. This work
      confirmed that up to 96% of the calcium of phosphogypsum could be recycled for
      CO2 mineral sequestration by a simple two-step process: alkaline dissolution and
      aqueous carbonation, under ambient pressure and temperature. This CO2
      sequestration process based on recycling phosphogypsum wastes would help to
      mitigate greenhouse gasses emissions. Yet this work goes beyond the validation of
      the sequestration procedure; it tracks the contaminants, such as trace metals or
      radionuclides, during the recycling process in the phosphogypsum. Thus, most of
      the contaminants were transferred from raw phosphogypsum to portlandite, obtained
      by dissolution of the phosphogypsum in soda, and from portlandite to calcite
      during aqueous carbonation. These findings provide valuable information for
      managing phosphogypsum wastes and designing potential technological applications
      of the by-products of this environmentally-friendly proposal. 

PMID- 26209346
TI  - Proliferative vitreoretinopathy: A new concept of disease pathogenesis and
      practical consequences.
AB  - During the last four decades, proliferative vitreoretinopathy (PVR) has defied
      the efforts of many researchers to prevent its occurrence or development. Thus,
      PVR is still the major complication following retinal detachment (RD) surgery and
      a bottle-neck for advances in cell therapy that require intraocular surgery. In
      this review we tried to combine basic and clinical knowledge, as an example of
      translational research, providing new and practical information for clinicians.
      PVR was defined as the proliferation of cells after RD. This idea was used for
      classifying PVR and also for designing experimental models used for testing many
      drugs, none of which were successful in humans. We summarize current information
      regarding the pathogenic events that follow any RD because this information may
      be the key for understanding and treating the earliest stages of PVR. A major
      focus is made on the intraretinal changes derived mainly from retinal glial cell
      reactivity. These responses can lead to intraretinal PVR, an entity that has not
      been clearly recognized. Inflammation is one of the major components of PVR, and
      we describe new genetic biomarkers that have the potential to predict its
      development. New treatment approaches are analyzed, especially those directed
      towards neuroprotection, which can also be useful for preventing visual loss
      after any RD. We also summarize the results of different surgical techniques and
      clinical information that is oriented toward the identification of high risk
      patients. Finally, we provide some recommendations for future classification of
      PVR and for designing comparable protocols for testing new drugs or techniques. 

PMID- 26209347
TI  - Direct N-terminal sequencing of polypeptides using a thermostable bacterial
      aminopeptidase and MALDI-TOF mass spectrometry.
AB  - Mass spectrometry-based amino acid sequencing is currently based almost entirely
      on collision-induced peptide fragmentation and analyses. Here, we describe a
      single-stage MS-based technique for amino acid sequencing involving partial,
      heterogenous digestion of a peptide by a processive, non-specific, heat-loving
      Bacillus subtilis-derived aminopeptidase (BsuAP), which acts optimally at 70 
      degrees C and allows 'single-shot' sequencing to be carried out through
      simultaneous accumulation, and detection of sub-populations of peptides of
      progressively reducing length. 

PMID- 26209348
TI  - Visualization of acetaminophen-induced liver injury by time-of-flight secondary
      ion mass spectrometry.
AB  - Time-of-flight secondary ion mass spectrometry (MS) provides secondary ion images
      that reflect distributions of substances with sub-micrometer spatial resolution.
      To evaluate the use of time-of-flight secondary ion MS to capture subcellular
      chemical changes in a tissue specimen, we visualized cellular damage showing a
      three-zone distribution in mouse liver tissue injured by acetaminophen overdose.
      First, we selected two types of ion peaks related to the hepatocyte nucleus and
      cytoplasm using control mouse liver. Acetaminophen-overdosed mouse liver was then
      classified into three areas using the time-of-flight secondary ion MS image of
      the two types of peaks, which roughly corresponded to established
      histopathological features. The ion peaks related to the cytoplasm decreased as
      the injury became more severe, and their origin was assumed to be mostly glycogen
      based on comparison with periodic acid-Schiff staining images and reference
      compound spectra. This indicated that the time-of-flight secondary ion MS image
      of the acetaminophen-overdosed mouse liver represented the chemical changes
      mainly corresponding to glycogen depletion on a subcellular scale. In addition,
      this technique also provided information on lipid species related to the injury.
      These results suggest that time-of-flight secondary ion MS has potential utility
      in histopathological applications. 

PMID- 26209349
TI  - Differential regulation of metabolic parameters by energy deficit and hunger.
AB  - AIMS: Hypocaloric diet decreases both energy expenditure (EE) and respiratory
      exchange rate (RER), affecting the efficacy of dieting inversely. Energy deficit
      and hunger may be modulated separately both in human and animal studies by drug
      treatment or food restriction. Thus it is important to separate the effects of
      energy deficit and hunger on EE and RER. METHODS: Three parallel and analogous
      experiments were performed using three pharmacologically distinct anorectic
      drugs: rimonabant, sibutramine and tramadol. Metabolic parameters of vehicle- and
      drug-treated and pair-fed diet-induced obese mice from the three experiments
      underwent common statistical analysis to identify effects independent of the
      mechanisms of action. Diet-induced obesity (DIO) test of tramadol was also
      performed to examine its anti-obesity efficacy. RESULTS: RER was decreased
      similarly by drug treatments and paired feeding throughout the experiment
      irrespective of the cause of reduced food intake. Contrarily, during the passive
      phase, EE was decreased more by paired feeding than by both vehicle and drug
      treatment irrespective of the drug used. In the active phase, EE was influenced
      by the pharmacological mechanisms of action. Tramadol decreased body weight in
      the DIO test. CONCLUSIONS: Our results suggest that RER is mainly affected by the
      actual state of energy balance; conversely, EE is rather influenced by hunger.
      Therefore, pharmacological medications that decrease hunger may enhance the
      efficacy of a hypocaloric diet by maintaining metabolic rate. Furthermore, our
      results yield the proposal that effects of anorectic drugs on EE and RER should
      be determined compared to vehicle and pair-fed groups, respectively, in animal
      models.

PMID- 26209350
TI  - Bilateral duplication of the internal auditory canal: a case with successful
      cochlear implantation.
AB  - We report a case of bilateral duplication of the internal auditory canal (IAC).
      An 11-month-old girl with congenital profound hearing loss was referred to our
      hospital. Imaging evaluations revealed bilateral IAC duplication, which contained
      the facial and cochleovestibular nerves in one canal, but no nerves in the other.
      She underwent cochlear implantation. At 5 months after surgery her hearing
      thresholds with the cochlear implant are 40 and 45dB at 2000 and 4000Hz,
      respectively. Bilateral duplicated IAC is extremely rare, with seven cases
      reported in the literature. This case represents a previously unreported type of
      IAC duplication, and is the first case in which cochlear implantation was
      successfully performed.

PMID- 26209351
TI  - Rigid bronchoscopy and balloon dilation for removal of aspirated thumbtacks: case
      series and literature review.
AB  - OBJECTIVE: Aspirated thumbtacks can pose unique challenges during removal due to
      their shape. In particular, the flanges of the thumbtack can readily become
      trapped by the bronchial mucosa during extrication. We describe our experience of
      three children from whom aspirated thumbtacks were removed using rigid
      bronchoscopy following balloon dilation of the airway to reduce bronchial mucosa
      entrapment. METHODS: This is a retrospective review of three pediatric
      otolaryngology cases. RESULTS: In all three cases, the thumbtack was successfully
      removed from various sites within the lower respiratory tract. There were no
      iatrogenic complications, in particular bronchial wall injury leading to
      pneumothorax. CONCLUSION: In cases of complicated airway foreign bodies, such as
      thumbtacks, airway dilation is a useful and safe maneuver that may help
      facilitate removal.

PMID- 26209352
TI  - The nature of articulation errors in Egyptian Arabic-speaking children with
      velopharyngeal insufficiency due to cleft palate.
AB  - Even with early surgical repair, the majority of cleft palate children
      demonstrate articulation errors and have typical cleft palate speech. OBJECTIVE:
      Was to determine the nature of articulation errors of Arabic consonants in
      Egyptian Arabic-speaking children with velopharyngeal insufficiency (VPI).
      SUBJECTS AND METHODS: Thirty Egyptian Arabic-speaking children with VPI due to
      cleft palate (whether primary repaired or secondary repaired) were studied.
      Auditory perceptual assessment (APA) of children speech was conducted.
      Nasopharyngoscopy was done to assess the velopharyngeal port (VPP) movements
      while the child was repeating speech tasks. Mansoura Arabic Articulation test
      (MAAT) was performed to analyze the consonants articulation of these children.
      RESULTS AND CONCLUSION: The most frequent type of articulatory errors observed
      was substitution, more specifically, backing. Pharyngealization of anterior
      fricatives was the most frequent substitution, especially for the /s/ sound. The
      most frequent substituting sounds for other sounds were /?/ followed by /k/ and
      /n/ sounds. Significant correlations were found between the degrees of the open
      nasality and VPP closure and the articulation errors. On the other hand, the
      sounds (/?/,/h/,/?/,/n/,/w/,/j/) were normally articulated in all studied group.
      The determination of articulation errors in VPI children could guide the
      therapists for designing appropriate speech therapy programs for these cases.

PMID- 26209353
TI  - [Tropical and imported infectious diseases. A challenge for primary care].

PMID- 26209354
TI  - Pre-treatment of allogeneic bone marrow recipients with the CXCR4 antagonist
      AMD3100 transiently enhances hematopoietic chimerism without promoting donor
      specific skin allograft tolerance.
AB  - Hematopoietic chimerism established by allogeneic bone marrow transplantation is
      known to promote donor-specific organ allograft tolerance; however, clinical
      application is limited by the need for toxic host conditioning and "megadoses" of
      donor bone marrow cells. A potential solution to this problem has been suggested
      by the observation that recipient bone marrow mobilization by the CXCR4
      antagonist AMD3100 promotes chimerism in congenic bone marrow transplantation
      experiments in mice. Here we report that a single subcutaneous dose of 10 mg/kg
      AMD3100 in recipient C57BL/6 mice was able to enhance hematopoietic chimerism
      when complete MHC-mismatched BALB/c donor bone marrow cells were transplanted 1h
      after drug dosing. However, levels of chimerism measured 30 days post
      transplantation were not sustained when mice were reexamined on day 90 post
      transplantation. Moreover, transient chimerism induced by this protocol did not
      support robust donor-specific skin allograft tolerance. Using the same transient
      immunosuppression protocol, we confirmed that "megadoses" of donor bone marrow
      cells could induce durable chimerism associated with donor-specific skin
      allograft tolerance without AMD3100 pre-treatment. We conclude that in this
      protocol AMD3100 pretreatment may empty bone marrow niches that become reoccupied
      by allogeneic donor hematopoietic progenitor cells but not by true long-lived
      donor hematopoietic stem cells, resulting in short-lived chimerism and failure to
      support durable donor-specific allograft tolerance.

PMID- 26209355
TI  - Monocytic MDSCs regulate macrophage-mediated xenogenic cytotoxicity.
AB  - BACKGROUND: Xenotransplantation is considered to be one of the most attractive
      strategies for overcoming the worldwide shortage of organs. However, many
      obstructions need to be overcome before it will achieve clinical use in patients.
      One such obstacle is the development of an effective immunosuppressive strategy.
      We previously reported that myeloid-derived suppressor cells (MDSCs), a
      heterogeneous population of progenitor and immature myeloid cells, suppress
      xenogenic CTL-mediated cytotoxicity. Because of their heterogeneous nature, MDSC
      can function via several suppressive mechanisms that disrupt both innate and
      adaptive immunity. Since macrophages play a pivotal role in the rejection of a
      xenograft, in this study, we evaluated the suppressive effects of MDSC against
      macrophage-mediated xenogenic rejection. MATERIALS AND METHODS: To evaluate the
      effect of monocyte-derived MDSCs on xenogenic immune reactions, a
      CFSE(carboxyfluorescein diacetate, succinimidyl ester)assay was employed to
      assess cytotoxicity. RESULTS: While, in the absence of activation, primed MDSCs
      had no detectable effect on macrophage-induced cytotoxicity against SEC cells,
      LPS-activated MDSCs were found to significantly suppress xenogenic cytotoxicity.
      A CFSE cytotoxicity assay revealed that MDSCs significantly suppressed macrophage
      induced cytotoxicity. Furthermore, an indoleamine 2,3 dioxygenase (IDO)
      inhibitor, 1-methyl tryptophan (1-MT), abolished the MDSC-induced suppression of
      macrophage-mediated xeno-rejection, indicating that MDSCs may suppress macrophage
      mediated cytotoxicity in an IDO-dependent manner. CONCLUSION: These findings
      indicate that MDSCs have great potential for immunosuppressing macrophage
      mediated xeno-rejection.

PMID- 26209356
TI  - A matter of attention: Crossmodal congruence enhances and impairs performance in
      a novel trimodal matching paradigm.
AB  - A novel crossmodal matching paradigm including vision, audition, and
      somatosensation was developed in order to investigate the interaction between
      attention and crossmodal congruence in multisensory integration. To that end, all
      three modalities were stimulated concurrently while a bimodal focus was defined
      blockwise. Congruence between stimulus intensity changes in the attended
      modalities had to be evaluated. We found that crossmodal congruence improved
      performance if both, the attended modalities and the task-irrelevant distractor
      were congruent. If the attended modalities were incongruent, the distractor
      impaired performance due to its congruence relation to one of the attended
      modalities. Between attentional conditions, magnitudes of crossmodal enhancement
      or impairment differed. Largest crossmodal effects were seen in visual-tactile
      matching, intermediate effects for audio-visual and smallest effects for audio
      tactile matching. We conclude that differences in crossmodal matching likely
      reflect characteristics of multisensory neural network architecture. We discuss
      our results with respect to the timing of perceptual processing and state
      hypotheses for future physiological studies. Finally, etiological questions are
      addressed.

PMID- 26209357
TI  - Age-related differences in the use of automatic and controlled processes in a
      situation of sustained attention.
AB  - Previous studies examining sustained attention ability in older adults have
      yielded inconsistent results: age-related decline in studies using traditionally
      formatted tasks (TFT), in which subjects have to respond to rare targets, and
      preservation in studies using Go/No-Go tasks, in which subjects have to withhold
      response to rare targets. The purpose of this study was to examine whether these
      discrepancies could be explained by a differential use of automatic and
      controlled processes according to age. To that end, we used two versions of the
      same task differing in response mode (TFT, Go/No-Go), and the event-related
      potential (ERP) technique. The within-task comparison first revealed that older
      adults exhibited a vigilance decrement in the TFT SART, while their performance
      actually improved in the Go/No-Go SART. Secondly, in both tasks, ERP results
      notably evidenced increased P2s and non-target P3s in older adults, components
      related to the allocation of attentional resources. Altogether, our results
      suggest that in both tasks older adults adopted a controlled processing mode,
      which resulted in opposite effects on performance according to the nature of the
      task. 

PMID- 26209358
TI  - Which visual functions depend on intermediate visual regions? Insights from a
      case of developmental visual form agnosia.
AB  - A key question in visual neuroscience is the causal link between specific brain
      areas and perceptual functions; which regions are necessary for which visual
      functions? While the contribution of primary visual cortex and high-level visual
      regions to visual perception has been extensively investigated, the contribution
      of intermediate visual areas (e.g. V2/V3) to visual processes remains unclear.
      Here I review more than 20 visual functions (early, mid, and high-level) of LG, a
      developmental visual agnosic and prosopagnosic young adult, whose intermediate
      visual regions function in a significantly abnormal fashion as revealed through
      extensive fMRI and ERP investigations. While expectedly, some of LG's visual
      functions are significantly impaired, some of his visual functions are
      surprisingly normal (e.g. stereopsis, color, reading, biological motion). During
      the period of eight-year testing described here, LG trained on a perceptual
      learning paradigm that was successful in improving some but not all of his visual
      functions. Following LG's visual performance and taking into account additional
      findings in the field, I propose a framework for how different visual areas
      contribute to different visual functions, with an emphasis on intermediate visual
      regions. Thus, although rewiring and plasticity in the brain can occur during
      development to overcome and compensate for hindering developmental factors, LG's
      case seems to indicate that some visual functions are much less dependent on
      strict hierarchical flow than others, and can develop normally in spite of
      abnormal mid-level visual areas, thereby probably less dependent on intermediate
      visual regions. 

PMID- 26209359
TI  - Discriminating somatic and germline mutations in tumor DNA samples without
      matching normals.
AB  - Tumor analyses commonly employ a correction with a matched normal (MN), a sample
      from healthy tissue of the same individual, in order to distinguish germline
      mutations from somatic mutations. Since the majority of variants found in an
      individual are thought to be common within the population, we constructed a set
      of 931 samples from healthy, unrelated individuals, originating from two
      different sequencing platforms, to serve as a virtual normal (VN) in the absence
      of such an associated normal sample. Our approach removed (1) >96% of the
      germline variants also removed by the MN sample and (2) a large number (2%-8%) of
      additional variants not corrected for by the associated normal. The combination
      of the VN with the MN improved the correction for polymorphisms significantly,
      with up to ~30% compared with MN and ~15% compared with VN only. We determined
      the number of unrelated genomes needed in order to correct at least as
      efficiently as the MN is about 200 for structural variations (SVs) and about 400
      for single-nucleotide variants (SNVs) and indels. In addition, we propose that
      the removal of common variants with purely position-based methods is inaccurate
      and incurs additional false-positive somatic variants, and more sophisticated
      algorithms, which are capable of leveraging information about the area
      surrounding variants, are needed for optimal accuracy. Our VN correction method
      can be used to analyze any list of variants, regardless of sequencing platform of
      origin. This VN methodology is available for use on our public Galaxy server. 

PMID- 26209360
TI  - Inhibition of cytochrome P450 2J2 by tanshinone IIA induces apoptotic cell death
      in hepatocellular carcinoma HepG2 cells.
AB  - Cytochrome P450 2J2 (CYP2J2) is highly expressed in human tumors and carcinoma
      cell lines, and has been implicated in the pathogenesis of human cancers. The aim
      of this study was to identify a compound that could inhibit the activity of
      CYP2J2, and to examine its anticancer activity. To identify CYP2J2 inhibitors, 10
      terpenoids obtained from plants were screened using astemizole as a CYP2J2 probe
      substrate in human liver microsomes (HLMs). Of these, tanshinone IIA dose
      dependently and non-competitively inhibited CYP2J2-mediated astemizole O
      demethylation activity. Tanshinone IIA significantly decreased viability of human
      hepatoma HepG2 cells and SiHa cervical cancer cells; however, it was not
      cytotoxic against mouse hepatocytes. Furthermore, treatment of cells with
      tanshinone IIA significantly increased apoptotic cell death rate, as shown by the
      increase in Annexin V-stained cell populations, Bcl-2 associated X protein
      (Bax)/B-cell lymphoma 2 (Bcl-2) ratio, and poly (ADP-ribose) polymerase 1 (PARP
      1) cleavage in HepG2 cells. Furthermore, the results of this study showed that
      tanshinone IIA significantly decreased HepG2 cell-based tumor growth in nude mice
      in a dose-dependent manner. On the other hand, the tanshinone IIA-induced
      apoptotic cell death rate was significantly attenuated by enhanced up-regulation
      of CYP2J2 expression. Thus, our data strongly suggest that tanshinone IIA exerts
      its anticancer effect by inhibiting CYP2J2 activity. 

PMID- 26209361
TI  - SIRT2 regulates microtubule stabilization in diabetic cardiomyopathy.
AB  - Stable microtubules (MTs) is involved the mechanism of diabetic cardiomyopathy
      (DCM), which is induced by acetylation of alpha-tubulin. The present study
      investigated whether SIRT2, a deacetylase, regulates MT stability through alpha
      tubulin deacetylation in DCM and whether the receptor of advanced glycation end
      products (AGEs) signaling pathway is involved in this effect. Type 1 diabetic
      mellitus (T1DM) rats model was established by a single intraperitoneal injection
      of streptozotocin (STZ, 65 mg/kg), and neonatal rat cardiomyocytes were also
      cultured. Heart function was detected by Doppler. MT stability was elevated by
      beta-tubulin expression density. The protein expression of SIRT2, acetylated
      alpha-tubulin and AGEs receptor were detected by immunohistochemistry or Western
      blots. The interaction of SIRT2 and acetylated alpha-tubulin was detected by Co
      immunoprecipitation. In an animal model of T1DM, Western blots and
      immunohistochemistry revealed downregulation of SIRT2 but upregulation of the
      acetylated alpha-tubulin protein. These effects were reduced by treatment of
      aminoguanidine, an inhibitor of AGEs production. HDAC6 expression did not
      regulated in heart. In primary cultures of neonatal rat cardiomyocytes, the AGEs
      treatment impaired the SIRT2/acetylated alpha-tubulin signaling pathway, and
      SIRT2-overexpression reversed the function of AGEs on cardiomyocytes. In
      addition, gene silencing of AGEs receptor alleviated the impairment effect of
      AGEs on cardiomyocytes. In conclusion, these data demonstrate that AGEs/AGEs
      receptor promote MT stabilization via the suppression of the SIRT2/acetylated
      alpha-tubulin signaling pathway in DCM development.

PMID- 26209362
TI  - A natural xanthone increases catalase activity but decreases NF-kappa B and lipid
      peroxidation in U-937 and HepG2 cell lines.
AB  - Mangiferin, a C-glycosyl xanthone, has shown anti-inflammatory, antioxidant, and
      anti-tumorigenic activities. In the present study, we investigated the molecular
      mechanism for the antioxidant property of mangiferin. Considering the role of
      nuclear transcription factor kappa B (NF-kappaB) in inflammation and
      tumorigenesis, we hypothesized that modulating its activity will be a viable
      therapeutic target in regulating the redox-sensitive ailments. Our results show
      that mangiferin blocks several inducers, such as tumor necrosis factor (TNF),
      lypopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA) or hydrogen
      peroxide (H2O2) mediated NF-kappaB activation via inhibition of reactive oxygen
      species generation. In silico docking studies predicted strong binding energy of
      mangiferin to the active site of catalase (-9.13 kcal/mol), but not with other
      oxidases such as myeloperoxidase, glutathione peroxidase, or inducible nitric
      oxide synthase. Mangiferin increased activity of catalase by 44%, but had no
      effect on myeloperoxidase activity in vitro. Fluorescence spectroscopy further
      revealed the binding of mangiferin to catalase at the single site with binding
      constant and binding affinity of 3.1*10(-7) M(-1) and 1.046 respectively.
      Mangiferin also inhibits TNF-induced lipid peroxidation and thereby protects
      apoptosis. Hence, mangiferin with its ability to inhibit NF-kappaB and increase
      the catalase activity may prove to be a potent therapeutic.

PMID- 26209363
TI  - Reducing Abeta load and tau phosphorylation: Emerging perspective for treating
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex, progressive neurological disorder
      affecting elderly population of above 65 years of age, characterized by failure
      of memory, loss of acquired skills leading to apraxia, agnosia, aphasia and
      frequent disturbances in emotion with interpersonal and social deterioration. The
      extracellular senile plaques and intracellular neurofibrillary tangles composed
      of amyloid beta protein and highly phosphorylated tau protein, the key components
      involved in pathogenesis of AD are considered as the pathological hallmark of
      this disease. This has led to immense development in the field of treatment for
      AD. Recent evidences suggest that removal of protein deposits from AD brains are
      the newer attempts for treating AD. The major developments in this direction are
      the amyloid and tau based therapeutics, which could hold the key to treatment of
      AD in the near future. Several putative drugs have been thoroughly investigated
      in preclinical studies, but many of them have failed to produce results in the
      clinical scenario. Therefore, failures from the past can be treated as lessons
      for the development of efficacious drugs. In addition to this, various non-
      pharmacological interventions and miscellaneous drugs are also being used now for
      combating the AD like disease progression. Thus, present review discusses about
      the disease modifying therapies together with the various non-pharmacological
      interventions and miscellaneous drugs for treating AD. 

PMID- 26209365
TI  - Phosphodiesterase inhibitor, pentoxifylline enhances anticancer activity of
      histone deacetylase inhibitor, MS-275 in human breast cancer in vitro and in
      vivo.
AB  - MS-275, a histone deacetylase inhibitor (HDACi), is undergoing clinical trials
      for treatment of various cancers. Pentoxifylline, a nonselective
      phosphodiesterase (PDE) inhibitor, has been shown to increase the effectiveness
      of antitumor chemotherapy. In the present study, the potential anti-cancer
      activity of MS-275 in combination with pentoxifylline in panel of cell lines and
      human breast cancer xenograft model were examined. A Panel of cancer cell lines
      were treated with MS-275 and pentoxifylline to determine their impact on cellular
      proliferation, cell cycle regulation, apoptosis, anti-angiogenesis. The in vivo
      activities of MS-275 and pentoxifylline were assessed in a Matrigel plug
      angiogenesis model and human breast cancer (MDA-MB-231) xenograft model.
      Combination of MS-275 with pentoxifylline showed enhanced anti-proliferative
      activity in a panel of cancer cell lines (HCT 116, MCF-7, PC3 and MDA-MB-231).
      Apoptotic studies performed using, Hoechst staining and cell cycle analysis
      reveal that this combination at the lower concentrations induces apoptosis
      downstream of the HDAC inhibition and PDE regulation. Further, combination showed
      enhanced antiangiogenic activity in Matrigel tube formation assay using HUVECs
      and in Matrigel plug assay in vivo. A significant inhibition (P<0.001) of tumor
      growth was observed in mice bearing MDA-MB-231 breast cancer xenograft treated
      with the combination of MS-275 (5mg/kg p.o.) and pentoxifylline (60 mg/kg i.p.)
      than treatments alone, without much signs of toxicity. Taken together, our study
      demonstrated enhanced anticancer activity of MS-275 and pentoxifylline
      combination both in vitro and in vivo with reduced toxicity. However, further
      studies are required to understand the mechanism for this combination effect.

PMID- 26209366
TI  - Investigation of optimal orthodontic force at the cellular level through three
      dimensionally cultured periodontal ligament cells.
AB  - OBJECTIVES: Optimal orthodontic force (OOF), important as it is, has generally
      been addressed at the level of tissue response. This study, for the first time,
      aimed to investigate its underlying mechanisms at the cellular level. METHODS:
      Human periodontal ligament tissue cells (PDLCs) were three-dimensionally (3D)
      cultured in a thin sheet of poly-lactic-co-glycolic acid (PLGA) scaffold. The 3D
      cultured PDLCs were treated with static compressive force of 0, 5, 15, and
      25g/cm(2) for 6, 24, and 72 hours, respectively. After that, methylthiazolyl
      tetracolium assay was done to evaluate the cell proliferation. The target gene
      expression in PDLCs was investigated through real-time PCR analysis. The
      conditioned media was collected for enzyme-linked immunosorbent assay (ELISA)
      assay, and also used for the coculture of osteoblasts and osteoclast precursors.
      Tartrate-resistant acid phosphatase (TRAP) staining was employed to examine
      osteoclasts. RESULTS: Compressive force inhibited proliferation of PDLCs in a
      magnitude-dependent manner. Heavier force upregulated expression of the
      osteoclastogenesis inducers, including RANKL, COX-2, PTHrP, and IL-11, more
      rapidly; however in the long run, no significant difference was found among
      different force magnitudes, either in the expression of osteoclastogenesis
      inducers by PDLCs, or in the osteoclast formation detected by TRAP staining.
      LIMITATIONS: The results regarding specific force magnitude as OOF should be
      confined to the present specific model, but not be extrapolated, without caution,
      to different in vitro models, nor even to in vivo studies or clinical
      application. CONCLUSIONS: Compared with heavier force, lighter force has similar
      pro-osteoclastogenic whilst less anti-proliferative effects on PDLCs, which
      provides a novel interpretation for OOF.

PMID- 26209364
TI  - Psychostimulants affect dopamine transmission through both dopamine transporter
      dependent and independent mechanisms.
AB  - The precise mechanisms by which cocaine and amphetamine-like psychostimulants
      exert their reinforcing effects are not yet fully defined. It is widely believed,
      however, that these drugs produce their effects by enhancing dopamine
      neurotransmission in the brain, especially in limbic areas such as the nucleus
      accumbens, by inducing dopamine transporter-mediated reverse transport and/or
      blocking dopamine reuptake though the dopamine transporter. Here, we present the
      evidence that aside from dopamine transporter, non-dopamine transporter-mediated
      mechanisms also participate in psychostimulant-induced dopamine release and
      contribute to the behavioral effects of these drugs, such as locomotor activation
      and reward. Accordingly, psychostimulants could increase norepinephrine release
      in the prefrontal cortex, the latter then alters the firing pattern of dopamine
      neurons resulting in changes in action potential-dependent dopamine release.
      These alterations would further affect the temporal pattern of dopamine release
      in the nucleus accumbens, thereby modifying information processing in that area.
      Hence, a synaptic input to a nucleus accumbens neuron may be enhanced or
      inhibited by dopamine depending on its temporal relationship to dopamine release.
      Specific temporal patterns of dopamine release may also be required for certain
      forms of synaptic plasticity in the nucleus accumbens. Together, these effects
      induced by psychostimulants, mediated through a non-dopamine transporter-mediated
      mechanism involving norepinephrine and the prefrontal cortex, may also contribute
      importantly to the reinforcing properties of these drugs. 

PMID- 26209367
TI  - Human respiratory syncytial virus in children with lower respiratory tract
      infections or influenza-like illness and its co-infection characteristics with
      viruses and atypical bacteria in Hangzhou, China.
AB  - BACKGROUND: Human respiratory syncytial virus (RSV) is the most important viral
      pathogen in children. However, its epidemic patterns and co-infection
      characteristics are not fully understood. OBJECTIVES: We attempted to determine
      the level of genetic variation of RSV, and describe the prevalence and co
      infection characteristics of RSV in Hangzhou during two epidemic seasons. STUDY
      DESIGN: Single respiratory samples from 1820 pediatric patients were screened for
      RSV and genotyped by RT-PCR and sequencing. In all RSV positive specimens, we
      screened for viruses and atypical bacteria. Demographic and clinical information
      was recorded and analyzed. RESULTS: A total of 34.5% and 3.8% of samples from
      acute lower respiratory tract infections (ALRI) and influenza-like illness (ILI)
      were positive for RSV, respectively. Phylogenetic analysis revealed that 61.1% of
      the selected 167 RSV strains were NA1, 31.1% were BA, 3.6% were ON1, 2.4% were
      CB1, and 1.8% were NA3. A new genotype, BA11 was identified, which comprised
      98.1% of BA strains in this study, while the rest were BA10. A total of 36.4% and
      9.1% of RSV-positive children with ALRI and ILI respectively were found to be co
      infected. Rhinovirus was the most common additional respiratory virus, followed
      by human metapneumovirus. Except for fever, no significant differences in other
      clinical presentation between the RSV mono-infection and co-infection groups were
      observed. CONCLUSIONS: The circulating RSV strains had high genetic variability
      with RSV-B showing a more local pattern. In ALRI cases, co-infection of RSV with
      other viruses or atypical bacteria has no significant effect on the clinical
      presentation except fever.

PMID- 26209368
TI  - Echovirus 30 meningitis epidemic followed by an outbreak-specific RT-qPCR.
AB  - BACKGROUND: An outbreak of enteroviral aseptic meningitis emerged in Southwestern
      Finland in August 2009. The same enterovirus reappeared with increasing incidence
      of meningitis in other parts of Finland in 2010. OBJECTIVES: To identify the
      incidence and molecular epidemiology of enteroviral meningitis outbreak. STUDY
      DESIGN: The causative agent was identified as echovirus 30 (E-30) by sequencing
      partial viral protein 1 capsid genome, and a virus type-specific RT-qPCR was set
      up for sensitive detection of the virus in cerebrospinal fluid specimens.
      Enterovirus positive CSF specimens were subjected to the E-30-specific assay to
      investigate this unusual occurrence of aseptic meningitis and facilitate case
      confirmation during the outbreaks between August 2009 and September 2010.
      RESULTS: E-30 was detected in 106 (72%) enterovirus positive cerebrospinal fluid
      specimens. All the meningitis cases in 2009 and most of them in 2010 were among
      adolescents and several were members of sport teams. CONCLUSIONS: Between August
      2009 and September 2010, E-30 caused an extensive outbreak with two peaks in
      Finland. Type-specific RT-PCR allowed rapid diagnostic follow-up of the epidemic.

PMID- 26209369
TI  - An outbreak of hepatitis A virus associated with a multi-national inner-city
      nursery in Glasgow, Scotland.
AB  - This report describes an outbreak of hepatitis A virus linked to a nursery which
      affected a total of 10 individuals. Active case finding, using oral fluid
      testing, helped identify asymptomatic cases. Nucleotide sequencing showed that
      all cases were caused by the same virus, which was most similar to HAV strains
      circulating Zimbabwe. Interestingly, an asymptomatic child had recently returned
      from visiting family in that country. Standard infection control procedures and
      vaccination of contacts successfully contained the outbreak. Only one patient
      developed hepatitis A despite having been vaccinated a week before symptoms
      began. This hepatitis A outbreak scenario may become more common as the numbers
      of international travellers and immigrants increase in the UK. It highlights the
      importance of recommending HAV vaccination to foreign nationals and their
      families who are travelling to countries endemic for hepatitis A. 

PMID- 26209370
TI  - Diagnostics-in-a-Suitcase: Development of a portable and rapid assay for the
      detection of the emerging avian influenza A (H7N9) virus.
AB  - BACKGROUND: In developing countries, equipment necessary for diagnosis is only
      available in few central laboratories, which are less accessible and of limited
      capacity to test large numbers of incoming samples. Moreover, the transport
      conditions of samples are inadequate, therefore leading to unreliable results.
      OBJECTIVES: The development of a rapid, inexpensive, and simple test would allow
      mobile detection of viruses. STUDY DESIGN: A suitcase laboratory "Diagnostics-in
      a-Suitcase" (56cm*45.5cm*26.5cm) containing all reagents and devices necessary
      for performing a reverse transcription recombinase polymerase amplification (RT
      RPA) assay was developed. As an example, two RT-RPA assays were established for
      the detection of hemagglutinin (H) and neuraminidase (N) genes of the novel avian
      influenza (H7N9) virus. RESULTS: The sensitivities of the H7 and the N9 RT-RPA
      assays were 10 and 100 RNA molecules, respectively. The assays were performed at
      a single temperature (42 degrees C). The results were obtained within 2-7min. The
      H7N9 RT-RPA assays did not show a cross-detection either of any other respiratory
      viruses affecting humans and/or birds or of the human or chicken genomes. All
      reagents were used, stored, and transported at ambient temperature, that is, cold
      chain independent. In addition, the Diagnostics-in-a-Suitcase was operated by a
      solar-powered battery. CONCLUSIONS: The developed assay protocol and mobile setup
      performed well. Moreover, it can be easily implemented to perform diagnoses at
      airports, quarantine stations, or farms for rapid on-site viral nucleic acid
      detection.

PMID- 26209371
TI  - Paediatric liver transplanted patients and prevalence of hepatitis E virus.
AB  - BACKGROUND: Hepatitis E is an emerging disease in developed countries and is
      usually asymptomatic, particularly in children. Chronic infection is possible in
      immunocompromised individuals. In the context of a liver transplant, it can
      simulate a rejection. In this case, antiviral therapy may be considered, thus
      highlighting the need to diagnose hepatitis E virus (HEV) infection in this
      population. OBJECTIVES: Given the lack of data in France, we have studied the the
      prevalence of antibodies to HEV in the paediatric liver transplant population.
      STUDY DESIGN: This was a retrospective study, carried out in Lyon between 1st
      January 2010 and 31 May 2013. HEV serology (anti-HEV IgM &IgG) and HEV PCR were
      studied in 96 children who had undergone liver transplants (84 isolated liver and
      12 combined liver and kidney transplants). RESULTS: Eight patients (8.3%; 62.5%
      girls; mean age:12.3 years) were HEV seropositive. The mean period since their
      transplantation was 10 years (range:2-21.8 years). Biliary atresia was the
      principal indication for transplantation. Seven of these eight children had
      received liver transplants. There were no differences between the epidemiological
      and clinical data concerning these patients and the remainder of the study
      population, particularly with respect to immunosuppression(7/8 tacrolimus; 50%
      dual immunosuppression). No cases of chronic hepatitis E were found, but 1/8 had
      chronic cytolysis(EBV&adenovirus infection). In all the patients tested(4/8),
      seroconversion had occurred after the transplant. There was no significant
      differences between the age groups in this study. CONCLUSIONS: This study showed
      that in France, the prevalence of antibodies to HEV in paediatric liver and
      combined liver and kidney transplant patients is 8.3%, as has been found by other
      European authors.

PMID- 26209372
TI  - Fatal cases of Chikungunya virus infection in Colombia: Diagnostic and treatment
      challenges.
AB  - Although Chikungunya infection is emerging as an important public health problem
      in many countries, it is not regarded as a life-threatening disease. Information
      dealing with fatal cases is scarce. We herein describe three patients with
      Chickungunya infection who presented with multiple organ failure and died within
      24h of admission. Two cases had positive anti-dengue IgM, but dengue coinfection
      was rejected based on the clinical features and results of real-time reverse
      transcription polymerase chain reaction. These cases illustrate the challenges of
      the diagnosis and management of severe Chikungunya infection. 

PMID- 26209373
TI  - Extra-pulmonary viral shedding in H7N9 Avian Influenza patients.
AB  - BACKGROUND: The clinical features of avian-origin influenza virus A (H7N9) virus
      infection have been extensively characterized, but viral RNA detection in extra
      pulmonary samples has seldom been studied. OBJECTIVES: To study shedding of viral
      RNA in extra pulmonary samples in patients with avian influenza H7N9 infections.
      STUDY DESIGN: A retrospective study of throat swabs, urine, fecal samples and
      sera collected sequentially from 18 hospitalized patients with H7N9 infections in
      Shanghai, China, between April and July in 2013 was conducted. RESULTS: Viral RNA
      could be detected in urine samples from 17 patients, in fecal samples from 15 and
      in sera from 14 with a real-time reverse transcription polymerase chain reaction.
      The median duration of shedding of viral RNA was 19.7 days in throat swabs, 22
      days in feces, 21.1 days in urines and 16.2 days in sera, indicating prolonged
      shedding of viral RNA in feces and urine compared with that in throat swabs.
      Prolonged duration of viral RNA detection in throat swabs and urine samples was
      observed in more severe patients. Moreover, in previously reported oseltamivir
      resistant patients, the NA gene with a 292K mutation could also be detected in
      their extra-pulmonary as well as in their respiratory samples. CONCLUSION: Our
      data indicated a high frequency of viral RNA detection in feces, urine and sera
      in H7N9-infected patients and pointed out the potential risk of transmission.

PMID- 26209374
TI  - Performance of HBsAg point-of-care tests for detection of diagnostic escape
      variants in clinical samples.
AB  - BACKGROUND: Hepatitis B viruses (HBV) harboring mutations in the a-determinant of
      the Hepatitis B surface antigen (HBsAg) are associated with reduced reactivity of
      HBsAg assays. OBJECTIVES: To evaluate the sensitivity and specificity of three
      HBsAg point-of-care tests for the detection of HBsAg of viruses harboring HBsAg
      mutations. STUDY DESIGN: A selection of 50 clinical plasma samples containing HBV
      with HBsAg mutations was used to evaluate the performance of three HBsAg point-of
      care tests (Vikia((r)), bioMerieux, Marcy-L'Etoile, France. Alere Determine
      HBsAgTM, Iverness Biomedical Innovations, Koln, Germany. Quick ProfileTM,
      LumiQuick Diagnostics, California, USA) and compared to the ARCHITECT HBsAg
      Qualitative((r)) assay (Abbott Laboratories, Sligo, Ireland). RESULTS: The
      sensitivity of the point-of-care tests ranged from 98% to 100%. The only false
      negative result occurred using the Quick ProfileTM assay with a virus harboring a
      D144A mutation. CONCLUSIONS: The evaluated point-of-care tests revealed an
      excellent sensitivity in detecting HBV samples harboring HBsAg mutations.

PMID- 26209375
TI  - Antibodies to VP1 of swine pasivirus in humans without evidence of transmission
      from a pig source.
AB  - BACKGROUND: Swine pasivirus (SPaV1) is a recently described enteric virus close
      to human parechoviruses and highly prevalent in pigs. Antibodies to Escherichia
      coli-expressed VP1 of SpaV1 have been found in a majority of humans in China.
      OBJECTIVES: The objectives were to estimate the antibody prevalence in a European
      country, to test if exposure to the virus was linked to pig products and if this
      exposure was a risk factor for the development of diabetes type 1. STUDY DESIGN:
      An ELISA test was developed and used to screen 842 healthy subjects with known
      exposure to pig products, 39 patients with diabetes type 1 and 20 controls.
      RESULTS: We identified a high seroprevalence (15.6%) reacting to VP1 of SPaV1
      among healthy human subjects. Analysis of risk factors argues against cross
      species transmission from pigs as the source of infection. Data also indicate
      that the presence of SPaV1 VP1-binding antibodies is not associated with diabetes
      type 1 in humans. CONCLUSION: Our results suggest that the seroreactivity
      frequently found in humans against SpaV1 is due to cross-reactivity with related
      antigen, perhaps a picornavirus, and that SpaV1 is not a zoonotic virus.

PMID- 26209376
TI  - HSV-2 meningoencephalitis in an immunocompetent young man: what is the
      pathogenesis and what is the treatment?
AB  - Herpes simplex encephalitis is rarely caused by herpes simplex virus type 2 (HSV
      2) after the neonatal period. The pathogenesis of HSV-2 encephalitis is not known
      and its treatment has not been discussed. We report a case of mild
      meningoencephalitis secondary to HSV-2 primary infection after sexual risk
      behaviour in a healthy young man. The diagnosis was established upon clinical,
      biological and electroencephalographic criteria. Aciclovir treatment led to rapid
      clinical improvement. This case highlights HSV-2 as a rare cause of
      meningoencephalitis, and questions the management of this rare manifestation of
      HSV-2 infection. 

PMID- 26209377
TI  - Acute human bocavirus infection in MDS patient, Cologne, Germany.

PMID- 26209378
TI  - Persistent viremia and urine shedding of tick-borne encephalitis virus in an
      infected immunosuppressed patient from a new epidemic cluster in North-Eastern
      Italy.
AB  - A persistent tick-borne encephalitis virus infection in an immune-suppressed
      patient is presented. Such an unusual clinical case offers the unique chance of
      detecting persistent viremia associated to the erythrocyte fraction and shedding
      of the virus in the urine for more than six weeks. The infection occurred in a
      new area of the Friuli Venezia-Giulia region (North Eastern Italy) where two
      additional cases are also being reported. 

PMID- 26209379
TI  - The reliability of high-risk human papillomavirus detection by Aptima HPV assay
      in women with ASC-US cytology.
AB  - BACKGROUND: The Aptima HPV assay (AHPV) for high-risk human papillomavirus
      (hrHPV), and the Aptima HPV 16 18/45 Genotype assay (AHPV GT) for HPV16 and for
      HPV18 and/or HPV45 (HPV18/45) genotypes are approved for cervical cancer
      screening by the U.S. Food and Drug Administration. There are limited data on the
      reliability of these tests for detection of hrHPV, HPV16, and HPV18/45.
      OBJECTIVES: To assess the reliability of AHPV and AHPV GT on paired specimens
      from women with atypical squamous cells of undetermined significance (ASC-US)
      cytology. STUDY DESIGN: In a population of women with ASC-US cytology (n=988),
      cervical specimens were collected at a routine screening baseline visit and at
      the colposcopy visit that occurred a median of 29 days later. Specimens were
      tested by AHPV and if positive, by AHPV GT. RESULTS: There was no significant
      difference in the percent AHPV positive between the colposcopy and baseline
      specimens (41.9% vs. 43.0%, respectively, p=0.3). The percent agreement, percent
      positive agreement, and the kappa value were 88.6%, 76.3%, and 0.766,
      respectively. There were no significant differences between AHPV testing of the
      colposcopy and baseline specimen in the sensitivity (95.2% vs. 92.9%,
      respectively, p=1) and specificity (60.5% vs. 59.2%, respectively, p=0.3) for
      CIN3+. Comparing the hierarchical AHPV and AHPV GT results on the two specimens,
      the percent exact agreement was 86.2%, the percent positive agreement was 68.4%,
      and the kappa value was 0.746. CONCLUSIONS: AHPV and AHPV GT demonstrated good
      reliability for hrHPV detection and risk stratification.

PMID- 26209380
TI  - Comparative performance of the new Aptima HIV-1 Quant Dx assay with three
      commercial PCR-based HIV-1 RNA quantitation assays.
AB  - BACKGROUND: Quantitative measurement of HIV-1 RNA levels in plasma ('viral load')
      plays a central role in clinical management. The choice of assay platform can
      influence results and treatment decisions. OBJECTIVE: To compare the analytical
      performance of the new TMA-based Hologic Aptima((r)) HIV-1 Quant Dx assay with
      that of three PCR-based assays: Abbott RealTime HIV-1, Qiagen Artus((r)) HI Virus
      1 QS-RGQ, and Roche CAP/CTM HIV-1 Test v2. STUDY DESIGN: Assay performance was
      evaluated using Acrometrix HIV-1 RNA Standard panels; the 3rd WHO HIV-1 RNA
      International Standard (12-500 copies/ml; 6 dilutions; 9 replicates); and plasma
      samples from 191 HIV-positive patients. RESULTS: Aptima showed high (>0.99)
      precision, accuracy and concordance with the Acrometrix Standards across a wide
      dynamic range (2.0-6.7 log10copies/ml). Variance caused up to 2.1 (Aptima), 1.7
      (RealTime), 7.5 (Artus), and 1.9 (CAP/CTM) fold changes in the International
      Standard quantifications at 50-500 copies/ml. HIV-1 RNA detection rates in plasma
      samples were 141/191 (74%), 119/191 (62%), 108/191 (57%), and 145/191 (76%) for
      Aptima, RealTime, Artus and CAP/CTM, respectively. For categorising samples
      either side of 50 copies/ml, Aptima had excellent agreement with RealTime (kappa
      0.92; 95% CI 0.87-0.98); lowest agreement was with Artus (kappa 0.79; 95%CI 0.70
      0.88). Aptima quantifications were mean 0.12 and 0.06 log10copies/ml higher
      compared with RealTime and CAP/CTM, respectively, and 0.05 log10copies/ml lower
      compared with Artus. Limits of agreement were narrowest when comparing Aptima to
      RealTime. CONCLUSIONS: The new Aptima HIV assay is sensitive, precise, and
      accurate. HIV assays exhibit discordance at low HIV-1 RNA copy numbers.

PMID- 26209381
TI  - Antibody avidity following secondary dengue virus type 2 infection across a range
      of disease severity.
AB  - BACKGROUND: The four dengue virus serotypes (DENV1-4) are responsible for the
      most prevalent mosquito-borne viral illness in humans. DENV causes a spectrum of
      disease from self-limiting dengue fever (DF) to severe, life-threatening dengue
      hemorrhagic fever/dengue shock syndrome (DHF/DSS). Antibodies from one infection
      can contribute to either protection or increased disease severity in a subsequent
      infection with a distinct DENV serotype. The effectiveness of the antibody
      response is modulated by both the affinity and avidity of the antibody/antigen
      interaction. OBJECTIVES: We investigated how antibody avidity developed over time
      following secondary DENV2 infection across different disease severities. STUDY
      DESIGN: We analyzed sera from 42 secondary DENV2-infected subjects (DF, n=15;
      DHF, n=16; DSS, n=11) from a pediatric hospital-based dengue study in Nicaragua.
      IgG avidity against DENV2 virions was measured in samples collected during acute
      and convalescent phases as well as 3, 6, and 18 months post-illness using a urea
      enzyme-linked immunosorbent assay. RESULTS: The data show a significant increase
      in avidity from acute to convalescent phase followed by a decrease from
      convalescent phase to 3 months post-symptom onset, then a plateau. Linear
      regression analysis comparing antibody avidity between disease severity groups
      over time indicate that individuals with more severe disease (DHF/DSS)
      experienced greater decay in antibody avidity over time compared to less severe
      disease (DF), and ROC curve analysis showed that at 18 months post-illness, lower
      avidity was associated with previously having experienced more severe disease.
      CONCLUSIONS: These data suggest that increased dengue disease severity is
      associated with lower antibody avidity at later time-points post-illness.

PMID- 26209382
TI  - The clinical significance of HCV core antigen detection during Telaprevir/Peg
      Interferon/Ribavirin therapy in patients with HCV 1 genotype infection.
AB  - BACKGROUND: Direct-acting antiviral drugs (DAA) regimen improve the SVR rate.
      However, adverse effects often lead to therapy interruption. This underlines the
      importance to find some predictive parameters of response in order to consider
      the possibility of a shorter time of antiviral treatment in the appearance of
      adverse effects without affecting the success of the therapy. OBJECTIVES: We
      aimed to examine the HCVAg kinetics in the early phase of treatment and its
      predictive value of SVR in patients undergoing TPV/Peg-IFN/RBV treatment. STUDY
      DESIGN: Twenty-three patients infected by HCV genotype 1 (1a n=11; 1b n=12) were
      included in this prospective study. RESULTS: At baseline the median Log of HCVAg
      concentration in RVR and EVR patients were 3.15 fmol/L and 3.45 fmol/L,
      respectively with no significant differences. The baseline median HCV-RNA to
      HCVAg ratio was 233.77, this ratio was significantly lower when measured on day 1
      (27.52) and on day 6 (24.84) (p<0.001). The two-tailed Fisher's exact test
      indicated that the SVR response is statistically significantly different in
      patients with detected HCVAg at week1 compared to patients with no detectable
      HCVAg (p=0.05). The sensitivity, specificity, and negative and positive
      predictive values (NPV, PPV) were 53.8, 87.5, 53.8 and 87.5%, respectively. The
      area under the ROC curve was 0.71 at day T6, the best cut-off of 3 fmol/L when
      evaluated with the HCVAg plasma concentration at day T6. CONCLUSION: Undetectable
      HCVAg in the early phase of TPV/Peg-IFN/RBV treatment could represent an
      important parameter for predicting SVR.

PMID- 26209383
TI  - Sofosbuvir-based therapy cures hepatitis C virus infection after prior treatment
      failures in a patient with concurrent lymphoma.
AB  - We report on the first well-tolerated and successful use of sofosbuvir-based
      therapy in a patient in whom chronic infection with hepatitis C had preceded the
      development of B-cell non-Hodgkin's lymphoma. The patient had previously failed
      numerous attempts to clear the hepatitis C virus with traditional antiviral
      schedules. We demonstrate that sofosbuvir-based therapy resulted in cure of
      hepatitis C in a patient who had relapsed during combination therapy with an NS5A
      inhibitor, an NS3 protease inhibitor and ribavirin, as well as treatment failures
      to multiple courses of interferon-based therapy. This report also suggests that
      eradication of hepatitis C virus may result in the short-term prevention of B
      cell non-Hodgkin's lymphoma relapse. The findings from our case require further
      validation in future cohorts of patients. 

PMID- 26209384
TI  - Absence of neutralizing antibodies against influenza A/H5N1 virus among children
      in Kamphaeng Phet, Thailand.
AB  - BACKGROUND: Influenza A/H5N1 actively circulated in Kamphaeng Phet (KPP),
      Thailand from 2004 to 2006. A prospective longitudinal cohort study of influenza
      virus infection in 800 adults conducted during 2008-2010 in KPP suggested that
      subclinical or mild H5N1 infections had occurred among this adult cohort.
      However, this study was conducted after the peak of H5N1 activity in KPP.
      Coincidentally, banked serum samples were available from a prospective
      longitudinal cohort study of primary school children who had undergone active
      surveillance for febrile illnesses from 2004 to 2007 and lived in the same
      district of KPP as the adult cohort. OBJECTIVES: We sought to investigate whether
      subclinical or mild H5N1 infections had occurred among KPP residents during the
      peak of H5N1 activity from 2004 to 2006. STUDY DESIGN: H5N1 microneutralization
      (MN) assay was performed on banked serum samples from a prospective longitudinal
      cohort study of primary school children who had undergone active surveillance for
      febrile illnesses in KPP. Annual blood samples collected from 2004 to 2006 from
      251 children were selected based on the criteria that they lived in villages with
      documented H5N1 infection. RESULT: No H5N1 neutralizing antibodies were detected
      in 753 annual blood samples from 251 children. CONCLUSION: During 2004-2006, very
      few subclinical or mild H5N1 infections occurred in KPP. Elevated H5N1 MN titers
      found in the adult cohort in 2008 were likely due to cross-reactivity from other
      influenza virus subtypes highlighting the complexities in interpreting influenza
      serological data.

PMID- 26209385
TI  - First international external quality assessment of molecular diagnostics for Mers
      CoV.
AB  - BACKGROUND: Since the discovery of Middle East respiratory syndrome coronavirus
      (MERS-CoV) in 2012, diagnostic protocols were quickly published and deployed
      globally. OBJECTIVES: We set out to assess the quality of MERS-CoV molecular
      diagnostics worldwide. STUDY DESIGN: Both sensitivity and specificity were
      assessed using 12 samples containing different viral loads of MERS-CoV or common
      coronaviruses (OC43, 229E, NL63, HKU1). RESULTS: The panel was sent to more than
      106 participants, of which 99 laboratories from 6 continents returned 189 panel
      results.Scores ranged from 100% (84 laboratories) to 33% (1 laboratory). 15% of
      respondents reported quantitative results, 61% semi-quantitative (Ct-values or
      time to positivity) and 24% reported qualitative results. The major specific
      technique used was real-time RT-PCR using the WHO recommended targets upE, ORF1a
      and ORF1b. The evaluation confirmed that RT-PCRs targeting the ORF1b are less
      sensitive, and therefore not advised for primary diagnostics. CONCLUSIONS: The
      first external quality assessment MERS-CoV panel gives a good insight in
      molecular diagnostic techniques and their performances for sensitive and specific
      detection of MERS-CoV RNA globally. Overall, all laboratories were capable of
      detecting MERS-CoV with some differences in sensitivity. The observation that 8%
      of laboratories reported false MERS-CoV positive single assay results shows room
      for improvement, and the importance of using confirmatory targets.

PMID- 26209386
TI  - Cytomegalovirus implicated in a case of progressive outer retinal necrosis
      (PORN).
AB  - Progressive outer retinal necrosis, also known as PORN, has been described as a
      variant of necrotizing herpetic retinopathy, occurring particularly in patients
      with acquired immune deficiency syndrome (AIDS). Although the etiologic organism
      has been reported to be Varicella-zoster virus, cytomegalovirus (CMV) can be an
      etiologic agent. Our case illustrates the occurrence of two opportunistic
      infections: PORN associated with CMV and Mycobacterium avium intracellulare
      duodenitis in a patient with uncontrolled HIV infection. 

PMID- 26209387
TI  - Dengue infection associated hemophagocytic syndrome: Therapeutic interventions
      and outcome.
AB  - Infection associated hemophagocytic syndrome is increasingly recognized as a
      potentially fatal complication of dengue fever. It should be suspected with
      prolonged fever beyond seven days associated with hepatosplenomegaly,
      hyperferritinemia, worsening cytopenias and development of multiorgan
      dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue
      associated hemophagocytic syndrome and multiorgan dysfunction may indicate they
      are part of related inflammatory spectrum. A proportion of patients recovered
      with supportive therapy, however most required interventions with
      corticosteroids, intravenous immunoglobulin or chemotherapy. We report three
      cases of dengue associated IAHS with good outcome following early recognition and
      treatment with dexamethasone and intravenous immunoglobulin. 

PMID- 26209388
TI  - The use of next generation sequencing in the diagnosis and typing of respiratory
      infections.
AB  - BACKGROUND: Molecular assays are the gold standard methods used to diagnose viral
      respiratory pathogens. Pitfalls associated with this technique include limits to
      the number of targeted pathogens, the requirement for continuous monitoring to
      ensure sensitivity/specificity is maintained and the need to evolve to include
      emerging pathogens. Introducing target independent next generation sequencing
      (NGS) could resolve these issues and revolutionise respiratory viral diagnostics.
      OBJECTIVES: To compare the sensitivity and specificity of target independent NGS
      against the current standard diagnostic test. STUDY DESIGN: Diagnostic RT-PCR of
      clinical samples was carried out in parallel with target independent NGS. NGS
      sequences were analyzed to determine the proportion with viral origin and
      consensus sequences were used to establish viral genotypes and serotypes where
      applicable. RESULTS: 89 nasopharyngeal swabs were tested. A viral pathogen was
      detected in 43% of samples by NGS and 54% by RT-PCR. All NGS viral detections
      were confirmed by RT-PCR. CONCLUSIONS: Target independent NGS can detect viral
      pathogens in clinical samples. Where viruses were detected by RT-PCR alone the Ct
      value was higher than those detected by both assays, suggesting an NGS detection
      cut-off - Ct=32. The sensitivity and specificity of NGS compared with RT-PCR was
      78% and 80% respectively. This is lower than current diagnostic assays but NGS
      provided full genome sequences in some cases, allowing determination of viral
      subtype and serotype. Sequencing technology is improving rapidly and it is likely
      that within a short period of time sequencing depth will increase in-turn
      improving test sensitivity.

PMID- 26209389
TI  - Persistent viral DNA detection in blood after primary herpes simplex 1 infection
      revealed by hepatitis with hemophagocytic syndrome.
AB  - We here report the case of a 52-year old man who presented hepatitis with
      hemophagocytic syndrome triggered by herpes simplex 1 (HSV-1) primary infection.
      A high-level viremia was observed, and HSV-1 DNA remained detectable in blood for
      a long time after patient's recovery. 

PMID- 26209390
TI  - Genomic characterization of a persistent rubella virus from a case of Fuch'
      uveitis syndrome in a 73 year old man.
AB  - BACKGROUND: Many cases of Fuchs' uveitis have been associated with persistent
      rubella virus infection. A 73-year-old male patient with typical Fuchs' Uveitis
      Syndrome (FUS) first experienced heterochromia of the left eye at the age
      fourteen, when rubella was endemic in the US. OBJECTIVES: The purposes of this
      report are to describe the patient's FUS clinical presentations and to
      characterize the virus detected in the vitreous fluid. STUDY DESIGN: The patient
      underwent a therapeutic pars plana vitrectomy in May 2013. A real-time RT-PCR
      assay for rubella virus was performed on the vitreous fluid by Focus Diagnostics.
      Additional real-time RT-PCR assays for rubella virus detection and RT-PCR assays
      for generation of templates for sequencing were performed at the Centers for
      Disease Control and Prevention (CDC). RESULTS: The results from Focus Diagnostics
      were positive for rubella virus RNA. Real-time RT-PCR assays at CDC were also
      positive for rubella virus. A rubella virus sequence of 739 nucleotides was
      determined and phylogenetic analysis showed that the virus was the sole member of
      a new phylogenetic group when compared to reference virus sequences. CONCLUSIONS:
      While FUS remains a clinical diagnosis, findings in this case support the
      association between rubella virus and the disease. Phylogenetic analysis provided
      evidence that this rubella virus was likely a previously undetected genotype
      which is no longer circulating. Since the patient had rubella prior to 1955, this
      sequence is from the earliest rubella virus yet characterized.

PMID- 26209391
TI  - T-lymphocyte subsets in lung transplant recipients: association between nadir CD4
      T-cell count and viral infections after transplantation.
AB  - BACKGROUND: Little is known about the kinetics of T-cell subsets in lung
      transplant recipients (LTR) and their association with the occurrence of
      opportunistic infections (OI). OBJECTIVES: To analyze the kinetics of T
      lymphocyte subsets in LTR and the association between nadir CD4 T-cell count and
      viral infections after transplantation. STUDY DESIGN: Serial measurements of
      peripheral blood CD4 and CD8 T-cell counts obtained during the first year post
      transplantation from 83 consecutive LTR and their correlation with both viral OI
      and community-acquired infections post-transplantation were retrospectively
      analyzed. RESULTS: LTR with a nadir CD4 T-cell count <200 cells/MUl had
      consistently lower CD4 and CD8 T-cell counts than LTR with a nadir CD4 T-cell
      count >200 cells/MUl (p<0.001). In LTR with a nadir CD4 T-cell count <200
      cells/MUl, the cumulative incidence of viral infections detected in peripheral
      blood and in bronchoalveolar lavage (BAL) samples was higher than in LTR with a
      nadir CD4 T-cell count >200 cells/MUl (p=0.0012 and p=0.0058, respectively). A
      nadir CD4 T-cell count <200 cells/MUl within the first three months post
      transplantation predicted a higher frequency of viral infectious episodes in BAL
      samples within the subsequent six month period (p=0.0066). CONCLUSIONS:
      Stratification of patients according to nadir CD4 T-cell count may represent a
      new and simple approach for early identification of patients at risk for
      subsequent virus infections.

PMID- 26209392
TI  - Enterovirus D68 disease and molecular epidemiology in Australia.
AB  - BACKGROUND: Enterovirus D68 (EV-D68) has received considerable recent attention
      as a cause of widespread respiratory illness. Neurological syndromes such as
      acute flaccid paralysis following EV-D68 infection have also been reported in a
      small number of cases. OBJECTIVES: To summarize the clinical and epidemiological
      characteristics of laboratory confirmed EV-D68 cases in Australia. STUDY DESIGN:
      We combined EV-D68 data acquired through laboratory surveillance in Western
      Australia with cases from national enterovirus surveillance and regional acute
      flaccid paralysis (AFP) surveillance. Clinical data was obtained for EV-D68 cases
      and capsid protein sequences were used for phylogenetic analysis. RESULTS:
      Sporadic cases of EV-D68 were recorded in Australia since 2008, with peaks in
      activity during 2011 and 2013. EV-D68 was primarily associated with respiratory
      disease, but was also detected in cerebrospinal fluid of one patient and faeces
      of two patients presenting with AFP. CONCLUSIONS: EV-D68 has been circulating in
      Western Australia and is likely to have also been present in the wider region for
      a number of years, causing primarily respiratory disease. Detection of EV-D68 in
      cerebrospinal fluid of one patient and in faeces of two AFP cases reinforces the
      association between EV-D68 and neurological disease.

PMID- 26209393
TI  - Purpuric herpes zoster in patients in therapy with clopidogrel.
AB  - Clopidogrel is an adenosine diphosphate receptor antagonist used for the
      prevention of vascular events in patients with atherothrombotic diseases
      manifested by recent myocardial infarction, ischemic stroke or peripheral
      arterial disease. Diarrhoea, rash and pruritus are rather common side effects of
      clopidogrel. Other side effects include epistaxis, nausea, abdominal pain,
      vomiting, gastritis, gastric and duodenal ulcer. Thrombocytopenia is the most
      common laboratory abnormality. Leucopenia and neutropenia are rare. We report
      three cases of purpuric herpes zoster in patients in therapy with clopidogrel. To
      our knowledge, only one case of haemorrhagic herpes zoster has been published in
      a patient in therapy with this drug. 

PMID- 26209394
TI  - Human metapneumovirus-associated severe acute respiratory illness hospitalisation
      in HIV-infected and HIV-uninfected South African children and adults.
AB  - BACKGROUND: Data on human metapneumovirus (HMPV)-associated severe acute
      respiratory illness (SARI) are limited in settings with high human
      immunodeficiency virus (HIV) infection prevalence. OBJECTIVES: To describe
      clinical characteristics and seasonality (all sites), and incidence (Soweto only)
      of HMPV-associated SARI among children and adults. STUDY DESIGN: Active,
      prospective, hospital-based, sentinel surveillance for patients hospitalised with
      SARI was conducted at four sites in South Africa from February 2009-December
      2013. Upper respiratory tract samples were tested by multiplex real-time
      polymerase chain reaction assays for HMPV and other respiratory viruses.
      Incidence of hospitalisation, stratified by age and HIV-infection status, was
      calculated for one hospital with population denominators. RESULTS: HMPV was
      identified in 4.1% of patients enrolled, including 5.6% (593/10503) in children
      and 1.7% in adults (>=18 years; 119/6934). The majority of adults (84.0%) had an
      underlying medical condition, including HIV infection in 87/110 (79.1%). HMPV
      detection occurred perennially with periods of increased detection, which varied
      from year to year. The incidence of HMPV-associated hospitalisation in Soweto was
      highest in infants (653.3 per 100,000 person years; 95% confidence interval (CI)
      602.2-707.6). The incidence was higher in HIV-infected persons compared to HIV
      uninfected persons in age-groups 5-17 years (RR 6.0; 1.1-20.4), 18-44 years (RR
      67.6; 38.0-132.6) and 45-64 years (RR 5.3; 3.4-8.3), while not differing in other
      age-groups. CONCLUSIONS: The burden of HMPV-associated SARI hospitalisation among
      adults occurred predominantly in HIV-infected persons. Among children, infants
      were at highest risk, with similar burden of hospitalisation in HIV-infected and
      HIV-uninfected children.

PMID- 26209395
TI  - Low serum levels of CCL5 are associated with longer duration of viral shedding in
      norovirus infection.
AB  - BACKGROUND: The mechanisms that determine the duration of fecal shedding of
      norovirus in humans have not been described in detail. OBJECTIVES: We
      investigated serum inflammatory mediator levels in relation to the duration of
      viral shedding in norovirus infection. STUDY DESIGN: A prospective cohort study
      of patients hospitalized with acute norovirus genogroup II infection. Rectal swab
      samples were obtained at inclusion and day 7, 14, 21 and 28. Serum levels of 42
      inflammatory mediators were determined with a Luminex-based cytokine assay. Sera
      from 20 healthy blood donors served as controls. RESULTS: Altogether, 28 patients
      (54% women, median age 83 years, median duration of symptoms 3 days) were
      included. Twelve subjects cleared the virus within 14 days and 16 were norovirus
      RNA positive for >21 days, constituting the two study groups ("rapid" vs. "slow"
      clearance). Individuals with norovirus infection had higher levels of IL-18,
      CXCL9, CXCL10, soluble IL-2 receptor and macrophage migration inhibitory factor
      (MIF), compared to controls (p<0.05), with the highest median concentrations in
      the slow clearance group. In contrast, CCL5 levels were lower in the slow
      compared to the rapid clearance group (median 54 vs. 134 ng/mL, p<0.05), and
      lower in norovirus-infected patients than in controls. CONCLUSION: Low levels of
      CCL5 were associated with longer duration of viral shedding, suggesting that CCL5
      may influence the clearance of norovirus.

PMID- 26209396
TI  - Restricted infection of murine cytomegalovirus (MCMV) in neonatal mice with MCMV
      induced sensorineural hearing loss.
AB  - BACKGROUND: Congenital infection with human Cytomegalovirus (HCMV) is known to be
      a causative agent of sensorineural hearing loss (SNHL). OBJECTIVES: To clarify
      the nongenetic etiology of SNHL by identifying the Cytomegalovirus (CMV)-infected
      region in the cochleae. STUDY DESIGN: We established an animal model of SNHL by
      injecting neonatal Balb/c mice with intracerebral murine Cytomegalovirus (MCMV)
      within 24h after delivery. RESULTS: At 3 weeks of age, unilateral and bilateral
      SNHL were observed in 24% (5/21) and 29% (6/21) of the mice, respectively. SNHL
      thereafter progressed, with 79% of mice developing bilateral SNHL by 6 weeks of
      age. MCMV antigens and DNA were detected in the spiral ganglion, and cells
      surrounding the meninges and scala tympani at 1 week of age. However, both MCMV
      antigens and DNA had completely disappeared by 2 weeks of age. It is possible
      that the MCMV reached the spiral ganglion via cerebrospinal fluid as the result
      of meningitis, as the stria vascularis was found to be MCMV antigen negative.
      Myosin VI expression in the outer hair cells was lost at 3 weeks of age. MCMV and
      myosin VI expression disappeared before and during SNHL progression,
      respectively. CONCLUSIONS: There was a definite lag time between the period in
      which MCMV antigens/DNA-positive cells were observed and that in which SNHL
      developed and myosin VI-negative hair cells were observed. Further study is
      needed to explore the role of MCMV in the loss of myosin VI expression in the
      outer hair cells.

PMID- 26209397
TI  - Expansion of the CRF19_cpx Variant in Spain.
AB  - BACKGROUND: HIV-1 CRF19_cpx, is a recombinant variant found almost exclusively in
      Cuba and recently associated to a faster AIDS onset. Infection with this variant
      leads to higher viral loads and levels of RANTES and CXCR4 co-receptor use.
      OBJECTIVES: The goal of this study was to assess the presence of CRF19_cpx in the
      Spanish province of Valencia, given its high pathogenicity. STUDY DESIGN: 1294
      HIV-1 protease-reverse transcriptase (PR/RT) sequences were obtained in Valencia
      (Spain), between 2005 and 2014. After subtyping, the detected CRF19_cpx sequences
      were aligned with 201 CRF19_cpx and 66 subtype D sequences retrieved from LANL,
      and subjected to maximum-likelihood phylogenetic analyses and Bayesian coalescent
      reconstructions. The presence of resistance mutations in the PR/RT region of
      these sequences was also analyzed. RESULTS: Among the 9 CRF19_cpx sequences from
      different patients found (prevalence <0.1%), 7 grouped in two well-supported
      clades (groups A, n=4, and B, n=3), suggesting the existence of at least two
      independent introductions which subsequently started to expand in the studied
      Spanish region. Unprotected sex between men was the only known transmission
      route. Coalescent analyses suggested that the introductions in Valencia occurred
      between 2008 and 2010. Resistance mutations in the RT region were found in all
      sequences from group A (V139D) and in two sequences from group B (E138A).
      CONCLUSIONS: This study reports for the first time the recent expansion of
      CRF19_cpx outside Cuba. Our results suggest that CRF19_cpx might become an
      emerging HIV variant in Spain, affecting Spanish native MSM and not only Cuban
      migrants.

PMID- 26209398
TI  - Identification of newly detected, drug-related HCMV UL97- and UL54-mutations
      using a modified plaque reduction assay.
AB  - BACKGROUND: Drug-resistant cytomegalovirus causes major problems in
      immunocompromised patients and is due to mutations in the UL97-gene
      (phosphotransferase) and/or the UL54-gene (polymerase). OBJECTIVE: Three
      previously unknown UL97-mutations (E596D/Y and I610T), one UL54 single point
      mutation (D515E) and a UL54 triple mutation (D515E+L516M+I521T) were
      characterized for drug-resistance by marker transfer analysis using BAC
      technology. STUDY DESIGN: Mutations were introduced into the bacterial artificial
      chromosome TB40-BACKL7-UL32EGFP. In addition, mutations M460V (UL97) and I521T
      (UL54) served as drug-resistant control. Phenotypic resistance testing was
      performed by a modified plaque reduction assay using a mixture of infected
      fibroblasts and uninfected ARPE-19 cells which improved formation of clearly
      definable plaques considerably. RESULTS: Resistance testing showed ganciclovir
      (GCV)-resistance for UL97-mutations I610T and E596Y while mutation E596D was drug
      sensitive. UL54-mutation D515E was resistant to GCV. The virus strain containing
      the UL54 triple mutation conferred cross-resistance to GCV and cidofovir (CDV).
      None of the mutations interfered with normal growth kinetics of the virus.
      CONCLUSIONS: New mutations in the UL97- and UL54-gene of HCMV are still detected
      continuously. Furthermore, several mutations occurring in the same codon often
      show divergent phenotypes and the accumulation of multiple mutations in one virus
      strain may lead to increased or decreased drug-resistance. Therefore,
      characterization of newly detected mutations by marker transfer analysis is
      essential to confirm that genotypically detected mutations can produce phenotypic
      resistance. These results allow reliable interpretation of fast genotypic methods
      generally used in diagnostics.

PMID- 26209399
TI  - Hepatitis E and neuralgic amyotrophy: Five cases and review of literature.
AB  - Hepatitis E virus infection - mainly genotype 3 - is increasingly common in
      industrialized countries. Infection is usually asymptomatic, but cases of central
      or peripheral neurological symptoms with hepatitis E have been described. The
      most frequent is Guillain-Barre but somes cases of neuralgic amyotrophy have been
      described. In our center, since 2010, we have identified five cases of neuralgic
      amyotrophy associated with acute hepatitis E in immunocompetent patients. For all
      these patients, neuralgic amyotrophy was diagnosed with electromyogram and
      positive IgM for hepatitis E, and detectable HEV RNA in 4 of the cases. Including
      our patients, we count 26 cases in literature. The mean age of the patients was
      44 years old, with a large predominance of males (88%). The disorder is bilateral
      and asymmetric in 69% of cases. Peripheral nerves other than the brachial plexus
      were affected in 6 patients (23%). In industrialized countries, any neuralgic
      amyotrophy, particularly if there is bilateral, asymmetric associated with
      involvement of nerves outside the brachial plexus, should lead physicians to
      consider a diagnosis of acute hepatitis E. 

PMID- 26209400
TI  - Application of bioinformatics in probe design enables detection of enteroviruses
      on different taxonomic levels by advanced in situ hybridization technology.
AB  - BACKGROUND: Enteroviral infections are common, affecting humans across all age
      groups. RT-PCR is widely used to detect these viruses in clinical samples.
      However, there is a need for sensitive and specific in situ detection methods for
      formalin-fixed tissues, allowing for the anatomical localization of the virus and
      identification of its serotype. OBJECTIVES: The aim was to design novel
      enterovirus probes, assess the impact of probe design for the detection and
      optimize the new single molecule in situ hybridization technology for the
      detection of enteroviruses in formalin-fixed paraffin-embedded samples. STUDY
      DESIGN: Four enterovirus RNA-targeted oligonucleotide RNA probes - two probes for
      wide range enterovirus detection and two for serotype-targeted detection of
      Coxsackievirus B1 (CVB1) - were designed and validated for the commercially
      available QuantiGene ViewRNA in situ hybridization method. The probe
      specificities were tested using a panel of cell lines infected with different
      enterovirus serotypes and CVB infected mouse pancreata. RESULTS: The two widely
      reactive probe sets recognized 19 and 20 of the 20 enterovirus serotypes tested,
      as well as 27 and 31 of the 31 CVB1 strains tested. The two CVB1 specific probe
      sets detected 30 and 14 of the 31 CVB1 strains, with only minor cross-reactivity
      to other serotypes. Similar results were observed in stained tissues from CVB 
      infected mice. CONCLUSIONS: These novel in-house designed probe sets enable the
      detection of enteroviruses from formalin-fixed tissue samples. Optimization of
      probe sequences makes it possible to tailor the assay for the detection of
      enteroviruses on the serotype or species level.

PMID- 26209401
TI  - Neutralization of Enterovirus D68 isolated from the 2014 US outbreak by
      commercial intravenous immune globulin products.
AB  - BACKGROUND: In 2014, an outbreak of Enterovirus D68 (EV-D68) was recorded as the
      largest in the US with cases confirmed in 49 states. Intravenous immune globulin
      (IVIG) has been used to treat enterovirus infections in neonates and is an
      accepted replacement therapy for immunodeficient patients. OBJECTIVES: This study
      aimed to detect the presence of neutralizing antibodies to EV-D68 viruses from
      the 2014 outbreak in commercially available IVIG products. STUDY DESIGN:
      Commercially available lots of IVIG preparations were obtained from five
      different manufacturers (2-10 preparations per manufacturer) and tested for
      neutralizing antibodies against the prototype EV-D68 virus and three EV-D68
      isolates representing strains circulating during the 2014 outbreak. RESULTS: All
      lots of IVIG tested were positive for EV-D68 neutralizing antibodies, with high
      titers ranging from 9.5log2 to 17.5log2, and with comparable median titers to all
      four EV-D68 viruses. CONCLUSIONS AND DISCUSSION: Amino acid sequence differences
      in the regions of the predicted antigenic sites on the viral capsid may explain
      some of the differences in neutralization among the different strains. The
      neutralization titers suggests that the 2014 outbreak EV-D68 viruses share some
      antigenic sites with the prototype virus and also present some unique antigenic
      sites distinct from the prototype. However, the commercial IVIG lots tested all
      contained high levels of neutralizing antibodies against EV-D68.

PMID- 26209402
TI  - Ganciclovir-resistant HHV-6 encephalitis that progressed rapidly after bone
      marrow transplantation.

PMID- 26209403
TI  - Cytomegalovirus load at treatment initiation is predictive of time to resolution
      of viremia and duration of therapy in hematopoietic cell transplant recipients.
AB  - BACKGROUND: Preemptive antiviral therapy relies on viral load measurements and is
      the mainstay of cytomegalovirus (CMV) prevention in hematopoietic cell transplant
      (HCT) recipients. However, optimal CMV levels for the initiation of preemptive
      therapy have not been defined. OBJECTIVES: The objectives of our work were to
      evaluate the relationship between plasma CMV DNA levels at initiation of
      preemptive therapy with time to resolution of viremia and duration of treatment.
      STUDY DESIGN: Retrospective analysis of HCT recipients undergoing serial CMV PCR
      testing between June 2011 and June 2014 was performed. RESULTS: 221 HCT
      recipients underwent preemptive therapy for 305 episodes of CMV viremia. Median
      time to resolution was shorter when treatment was initiated at lower CMV levels
      (15 days at 135-440 international units (IU)/mL, 18 days at 441-1000 IU/mL, and
      21 days at >1000 IU/mL, P<.001). Prolonged viremia lasting >30 days occurred less
      frequently when treatment was initiated at 135-440 IU/mL compared to 441-1000
      IU/mL and >1000 IU/mL (1%, 15%, 24%, P<.001). Median treatment duration was also
      shorter in the lower viral load groups (28, 34, 37 days, P<.001). CONCLUSION:
      Initiation of preemptive therapy at low CMV levels was associated with shorter
      episodes of viremia and courses of antiviral therapy. These data support the
      utility of initiating preemptive CMV therapy at viral loads as low as 135 IU/mL
      in HCT recipients.

PMID- 26209404
TI  - Roles of ITPA and IL28B genotypes in chronic Hepatitis C patients treated with
      peginterferon plus ribavirin in Tunisian population.
AB  - BACKGROUND: Despite considerable progress in the treatment of chronic hepatitis
      C, many countries do not have access to these new treatments. OBJECTIVES:
      Predictive markers of response to treatment are therefore necessary before
      initiating with historical combination therapy (PEG-IFN+ribavirin) for these
      populations. STUDY DESIGN: We therefore evaluated the influence of IL28B
      polymorphisms on treatment response and Inosine Triphosphate (ITPA) polymorphisms
      on the incidence of anaemia in a population of 120 Tunisian patients infected
      with HCV genotype 1b and treated. RESULTS: The frequencies of favourable IL28B
      genotypes were 47% (CC for rs12979860) and 63% (TT for rs8099117). Patients in
      whom favourable IL28B alleles were identified had a higher chance of successful
      therapy: 82% for CC (rs12979860) and 75% for TT (rs8099117). Viral load decline
      during the first twelve weeks of treatment was more pronounced in patients with a
      favourable genotype (p<0.0001). For patients with an unfavourable genotype, the
      second phase of viral decline was more pronounced in patients with SVR. A viral
      load decline cut-off of 2.68logIU/mL at week 12 was best suited to discriminate
      responders from non-responders with an odds ratio of 40 (95% CI:11.53-170.3).
      Analysis of ITPA polymorphisms revealed that 16% of Tunisian patients presented
      ITPase deficiency. None of these patients experienced a decline of ribavirin
      doses during treatment versus 67% for patients without ITPase deficiency
      (p<0.001). CONCLUSION: These data obtained in a Tunisian population should
      optimize before and during treatment the chances of success for treatments
      currently available in Tunisia for chronic HCV infection.

PMID- 26209405
TI  - Pathogen transcriptional profile in nasopharyngeal aspirates of children with
      acute respiratory tract infection.
AB  - BACKGROUND: Acute respiratory tract infections (ARI) present a significant
      morbidity and pose a global health burden. Patients are frequently treated with
      antibiotics although ARI are most commonly caused by virus, strengthening the
      need for improved diagnostic methods. OBJECTIVES: Detect viral and bacterial RNA
      in nasopharyngeal aspirates (NPA) from children aged 6-23 months with ARI using
      nCounter. STUDY DESIGN: A custom-designed nCounter probeset containing viral and
      bacterial targets was tested in NPA of ARI patients. RESULTS: Initially, spiked
      control viral RNAs were detectable in >=6.25 ng input RNA, indicating absence of
      inhibitors in NPA. nCounter applied to a larger NPA sample (n=61) enabled the
      multiplex detection of different pathogens: RNA viruses Parainfluenza virus (PIV
      1-3) and RSV A-B in 21%, Human metapneumovirus (hMPV) in 5%, Bocavirus (BoV),
      CoV, Influenza virus (IV) A in 3% and, Rhinovirus (RV) in 2% of samples,
      respectively. RSV A-B was confirmed by Real Time PCR (86.2-96.9% agreement). DNA
      virus (AV) was detected at RNA level, reflecting viral replication, in 10% of
      samples. Bacterial transcripts from Staphylococcus aureus, Haemophilus
      influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Mycoplasma
      pneumoniae and Chlamydophila pneumoniae were detected in 77, 69, 26, 8, 3 and 2%
      of samples, respectively. CONCLUSION: nCounter is robust and sensitive for the
      simultaneous detection of viral (both RNA and DNA) and bacterial transcripts in
      NPA with low RNA input (<10 ng). This medium-throughput technique will increase
      our understanding of ARI pathogenesis and may provide an evidence-based approach
      for the targeted and rational use of antibiotics in pediatric ARI.

PMID- 26209406
TI  - An unusual case of dengue infection presenting with hypokalemic paralysis with
      hypomagnesemia.
AB  - Neurological manifestations are unusual in dengue fever and can be due to
      neurotropic effect, systemic complications of dengue infection, or immune
      mediated. Acute hypokalemic paralysis is a rare systemic complication of dengue
      infection; however, hypokalemia along with hypomagnesemia has not been reported
      earlier. We herein report an extremely unusual and probably the first case of
      dengue infection in a 30-year-old male who presented to us with hypokalemic
      paralysis along with hypomagnesemia. This case report highlights that
      hypomagnesemia may be a significant complication in dengue infection. Correction
      of hypomagnesemia is of paramount importance to avoid refractory hypokalemia
      leading to severe consequences. 

PMID- 26209407
TI  - The virologist and the flu.
AB  - We report a case of a virologist - who is in age-appropriate medical condition
      with no relevant chronic diseases - who shed influenza A H3N2 virus RNA for 70
      days while infectious virus could be detected by cell culture only up to 5 days
      after onset of symptoms despite a 5-day course of oseltamivir. The case might
      have implications for infection control in hospital settings and the weighting of
      the predictive value of PCR results. 

PMID- 26209408
TI  - Identification of a duplicated V3 domain in NS5A associated with cirrhosis and
      hepatocellular carcinoma in HCV-1b patients.
AB  - BACKGROUND: The NS5A protein of the hepatitis C virus has been shown to be
      involved in the development of hepatocellular carcinoma. OBJECTIVES: In a French
      multicenter study, we investigated the clinical and epidemiological features of a
      new HCV genotype 1b strain bearing a wide insertion into the V3 domain. STUDY
      DESIGN: We studied NS5A gene sequences in 821 French patients infected with
      genotype 1b HCV. RESULTS: We identified an uncharacterized V3 insertion without
      ORF disruption in 3.05% of the HCV sequences. The insertion comprised 31 amino
      acids for the majority of patients; 3 patients had 27 amino-acids insertions and
      1 had a 12 amino-acids insertion. Sequence identity between the 31 amino-acids
      insertions and the V3 domain ranged from 48 to 96% with E-values above 4e(-5),
      thus illustrating sequence homology and a partial gene duplication event that to
      our knowledge has never been reported in HCV. Moreover we showed the presence of
      the duplication at the time of infection and its persistence at least during 12
      years in the entire quasispecies. No association was found with extrahepatic
      diseases. Conversely, patients with cirrhosis were two times more likely to have
      HCV with this genetic characteristic (p=0.04). Moreover, its prevalence increased
      with liver disease severity (from 3.0% in patients without cirrhosis to 9.4% in
      patients with both cirrhosis and HCC, p for trend=0.045). CONCLUSIONS: We
      identified a duplicated V3 domain in the HCV-1b NS5A protein for the first time.
      The duplication may be associated with unfavorable evolution of liver disease
      including a possible involvement in liver carcinogenesis.

PMID- 26209409
TI  - A pilot study to compare dry cervical sample collection with standard practice of
      wet cervical samples for human papillomavirus testing.
AB  - BACKGROUND: For human papillomavirus (HPV) DNA detection, specimen collection and
      transportation using a dry swab without transport medium has advantages, in
      various situations, over liquid media. OBJECTIVE: In this pilot study we
      evaluated whether a dry cervical sample taken with a flocked swab (dry sample) is
      a valid alternative for HPV DNA testing compared with the standard practice of a
      wet sample taken with a cyto-broom placed directly into liquid media (wet
      sample). STUDY DESIGN: Women attending the dysplasia clinic at the Royal Women's
      Hospital, Melbourne Australia between November 2013 and February 2014 were
      enrolled. During colposcopic examination, a practitioner collected wet and dry
      cervical samples, with the order of collection randomised. In the laboratory both
      samples were left for a week before being tested for 14 high-risk HPV types using
      the Roche Cobas 4800 test. RESULTS: Overall, 209 had valid HPV results from both
      samples. The observed agreement for HPV detection between wet and dry samples was
      92.8% and kappa was 0.85 (95% confidence interval (95% CI): 0.78-0.92). There was
      no statistical difference in the percent HPV positive for each sample (p = 0.30).
      HPV testing of the dry sample had an 88.5% (95% CI: 79.9-94.3%) sensitivity for
      HPV detected using the wet specimen. For the HPV results categorized
      hierarchically, there was 92.8% overall agreement and a kappa of 0.87 (95% CI =
      0.80-0.93) for the paired results. CONCLUSION: Using dry flocked swabs to collect
      cervical cells is a valid alternative to collecting wet samples for HPV DNA
      testing using a PCR based test.

PMID- 26209410
TI  - Immune status of health care workers to measles virus: evaluation of protective
      titers in four measles IgG EIAs.
AB  - BACKGROUND: Following the recognition of a measles case in a hospital in The
      Netherlands, health care workers (HCW) from the premises were screened by a
      commercial enzyme immunoassay (EIA) for measles IgG to identify persons at risk
      for measles. At least 10% of the HCW were tested measles IgG-negative. As this
      was considered an unusually high proportion, we hypothesized suboptimal
      sensitivity of EIAs, especially in medical personnel that had vaccine-induced
      immunity rather than antibodies resulting from natural infection. OBJECTIVES: To
      determine (vaccine-induced) measles immunity in HCW, using different EIAs
      compared to the plaque reduction neutralization (PRN) test, the best surrogate
      marker for vaccine efficacy and immune protection. STUDY DESIGN: Sera from HCW
      were tested for measles IgG antibodies in three commercial EIAs, in a bead-based
      multiplex immunoassay (MIA) and in the PRN test, and evaluated against age and
      vaccination history of the HCW. RESULTS: Of the 154 HCW, born between 1960 and
      1995, 153 (99.4%) had protective levels of measles antibodies (PRN> 120mIU/ml).
      The three EIAs failed to detect any measles IgG antibodies in approximately 10%
      of the HCW, while this percentage was approximately 3% for the MIA. Negative IgG
      results rose to 19% for individuals born between 1975 and 1985, pointing to an
      age group largely representing vaccinated persons from the first measles
      vaccination period in The Netherlands. CONCLUSION: The results show limitations
      in the usefulness of current EIA assays for determining protective measles
      antibodies in persons with a vaccination history.

PMID- 26209411
TI  - Molecular characterization of Anaplasma marginale in ticks naturally feeding on
      buffaloes.
AB  - Anaplasma marginale is the most prevalent pathogen transmitted by ticks in cattle
      in tropical and subtropical regions of the world. However, the tick species
      involved in the transmission of A. marginale in buffaloes in Brazil have not been
      identified. The objective of the present study was to determine the presence of
      A. marginale in ticks parasitizing water buffaloes. A total of 200 samples of
      Rhipicephalus microplus, Dermacentor nitens, Amblyomma cajennense, and Amblyomma
      maculatum were collected and tested by conventional and quantitative PCR for the
      presence of the msp1a and msp5 genes. In the present study, 35 ticks (17.5%) were
      positive for A. marginale DNA by qPCR analysis. The positive ticks belonged to
      four different species: R. microplus (22.2%), A. cajennense (13.8%), A. maculatum
      (16.0%), and D. nitens (10.0%). Individuals of the three developmental stages
      (larvae, nymphs, and adults) of R. microplus and A. cajennense were found to be
      positive for A. marginale, only nymphs and adults of A. maculatum were found to
      be positive, and finally, only adults of D. nitens were positive for A.
      marginale. Our results suggest that R. microplus, A. cajennense, A. maculatum,
      and D. nitens ticks may be involved in the transmission of A. marginale in
      buffaloes. However, while A. marginale PCR positive ticks were recorded, this
      does not indicate vector competence; only that the ticks may contain a blood meal
      from an infected host. Additionally, the results show that the strains of A.
      marginale from buffaloes and cattle are phylogenetically related. 

PMID- 26209412
TI  - Leydig cell hyperplasia in the setting of Klinefelter syndrome.
AB  - A man in his 20's with Klinefelter syndrome presented to the urology clinic with
      a recent history of left-sided orchalgia. Ultrasound evaluation demonstrated
      multiple small hypoechoic lesions bilaterally, with the largest lesion measured
      at 5 mm * 6 mm * 8 mm. Testis cancer tumour markers, chest radiographs and
      abdominal CT imaging were negative. A partial orchiectomy was performed on the
      largest lesion, demonstrating the presence of Leydig cell hyperplasia.

PMID- 26209413
TI  - PoMo: An Allele Frequency-Based Approach for Species Tree Estimation.
AB  - Incomplete lineage sorting can cause incongruencies of the overall species-level
      phylogenetic tree with the phylogenetic trees for individual genes or genomic
      segments. If these incongruencies are not accounted for, it is possible to incur
      several biases in species tree estimation. Here, we present a simple maximum
      likelihood approach that accounts for ancestral variation and incomplete lineage
      sorting. We use a POlymorphisms-aware phylogenetic MOdel (PoMo) that we have
      recently shown to efficiently estimate mutation rates and fixation biases from
      within and between-species variation data. We extend this model to perform
      efficient estimation of species trees. We test the performance of PoMo in several
      different scenarios of incomplete lineage sorting using simulations and compare
      it with existing methods both in accuracy and computational speed. In contrast to
      other approaches, our model does not use coalescent theory but is allele
      frequency based. We show that PoMo is well suited for genome-wide species tree
      estimation and that on such data it is more accurate than previous approaches. 

PMID- 26209414
TI  - Effects of condylar head surface changes on mandibular position in patients with
      temporomandibular joint osteoarthritis.
AB  - PURPOSE: This study evaluated condylar surface changes in patients after
      temporomandibular (TMJ) osteoarthritis (OA) treatment, and used cone beam
      computed tomography (CBCT) to investigate the relationship between condylar
      surface and mandibular position changes. MATERIAL AND METHODS: Thirty-six
      patients diagnosed with TMJ OA and receiving non-surgical treatments for TMJ OA
      were enrolled in this study. Patients were assigned to study groups according to
      the affected side. Those in the unilateral osteoarthritis (OAU) group (n = 20; 8
      males and 12 females; aged 22.0 +/- 11.5 years) had a unilateral condyle with TMJ
      OA, and those in the OAB group had bilateral TMJ OA (n = 16; 1 male and 15
      females; aged 25.7 +/- 6.4 years). Condylar surface and mandibular position
      changes were investigated by the superimposition of three-dimensional
      reconstructed images and CBCT data, respectively. RESULTS: For condylar surface
      changes, the average absolute deviation was 0.32 +/- 0.08 mm for the OA side and
      0.18 +/- 0.03 mm for the non-OA side, a significant difference between sides (p <
      0.05). In the bilateral osteoarthritis (OAB) group, the average absolute
      deviation was 0.35 +/- 0.08 mm for the left side and 0.33 +/- 0.09 mm for the
      right side. For mandibular position changes, measurement points that moved more
      than 2 mm were Pog, Me, and Mental foramen in both groups. CONCLUSION: The study
      results show that the mandible with both condyles affected moved backward and
      downward after TMJ OA treatment. In the patient ngroup with unilateral TMJ OA,
      there was deviation on the affected side and downward movement (p < 0.05).

PMID- 26209415
TI  - Assessing cardiac arrest beyond hospital discharge--We are only as "Good" as the
      outcomes we measure.

PMID- 26209416
TI  - Impedance threshold device (ITD) during cardiac arrest--Does it work or not?

PMID- 26209417
TI  - Kids save lives--Training school children in cardiopulmonary resuscitation
      worldwide is now endorsed by the World Health Organization (WHO).

PMID- 26209418
TI  - We need to move more: Neurobiological hypotheses of physical exercise as a
      treatment for Parkinson's disease.
AB  - Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases
      in the world. The degeneration of dopaminergic neurons in the substantia nigra
      and chronic inflammation impair specific brain areas, which in turn result in
      lesser motor control, behavioral changes and cognitive decline. Nowadays, drug
      treatments are the foremost approaches in treating PD. However, exercise has been
      shown to have powerful effects on PD, based on several neurobiological
      mechanisms. These effects may decrease the risk of developing PD by 33%. However,
      these mechanisms are unclear and little explored. Among several mechanisms, we
      propose two specific hypotheses: 1. Physical exercise reduces chronic oxidative
      stress and stimulates mitochondria biogenesis and up-regulation of authophagy in
      PD patients. Moreover, antioxidant enzymes (e.g. superoxide dismutase) become
      more active and effective in response to physical exercise. 2. Exercise
      stimulates neurotransmitter (e.g. dopamine) and trophic factors (BDNF, GDNF, FGF
      2, IGF-1, among others) synthesis. These neurochemical phenomena promote
      neuroplasticity, which, in turn, decreases neural apoptosis and may delay the
      neurodegeneration process, preventing or decreasing PD development and symptoms,
      respectively. 

PMID- 26209419
TI  - Double sentinel lymph node mapping with indocyanine green and 99m-technetium-tin
      colloid in oral squamous cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) frequently metastasizes to cervical lymph
      nodes, which is the most known prognostic factor. Screening methods to identify
      sentinel lymph nodes (SLNs) are therefore of great interest for the management of
      potential neck metastasis. The purpose of this study was to evaluate the clinical
      benefit of double SLN mapping with indocyanine green (ICG) and 99m-technetium-tin
      colloid ((99m)Tc-tin colloid) for sentinel node navigation surgery (SNNS).
      Between 2007 and 2010, 16 patients diagnosed with OSCC were investigated by SLN
      biopsy using the double mapping method. (99m)Tc-tin colloid was injected into the
      peri-tumoural region on the preoperative day, and ICG was administered
      intraoperatively in the same position to assist in detecting nodes during
      surgery. Based on the gamma-ray signal and near-infrared (NIR) fluorescence of
      ICG, SLNs were identified and thereafter assessed pathologically and genetically
      for cancer involvement. Radio-guided detection was successful for all patients.
      ICG mapping identified a relatively larger number of nodes, suggesting that
      several non-SLNs were potentially involved. The double mapping method assisted
      surgeons to explore SLNs. Since the ICG fluorescence was shielded by the
      subcutaneous fatty tissue and the muscle layer including platysma and
      sternocleidomastoid, it was necessary to retract the tissue away from nodes.

PMID- 26209420
TI  - Metal biouptake by actively growing cells of metal-tolerant bacterial strains.
AB  - Metal uptake potentials of Pseudomonas aeruginosa CA207Ni, Burkholderia cepacia
      CA96Co, Rhodococcus sp. AL03Ni, and Corynebacterium kutscheri FL108Hg were
      studied to determine their competence in detoxification of toxic metals during
      growth. Metabolism-dependent metal biouptake of the bacteria revealed appreciable
      uptake of the metals (57-61, 10-30, 23-60, and 10-16 mg g dw(-1) of Ni(2+),
      Cr(6+), Co(2+), and Cd(2+), respectively) from medium, after initial drop in pH,
      without lag phase. The bacteria exhibited 95-100% removal efficiency for the
      metals from aqueous medium as 21 (+/-0.8)-84 (+/-2.0) concentration factors of
      the metals were transported into the bacterial systems. Passive adsorption onto
      the cell surfaces occurred within 2-h contact, and afterwards, there was
      continuous accumulation for 12 days. Biosorption data of the bacteria were only
      fitted into Langmuir isotherm model when strains AL96Co, CA207Ni, and AL03Ni
      interacted with Ni(2+), achieving maximum uptake of 9.87, 2.72, and 2.69 mg g dw(
      1), respectively. This study established that the actively growing bacterial
      strains displayed, at least, 97.0% (+/-1.5) continuous active removals of metals
      upon adsorption. The bacteria would be good candidates for designing bioreactor
      useful in the detoxification campaign of heavy metal-polluted systems.

PMID- 26209421
TI  - Alcohol and Chronic Disease: Doubt Remains About Evidence But Not About
      Prevention.

PMID- 26209422
TI  - The effect of trunk extension on physiological cost index in spinal cord injury
      patients when using the advanced reciprocating gait orthosis: A pilot study.
AB  - BACKGROUND: People with spinal cord injury walk with a flexed trunk when using
      reciprocating gait orthoses for walking. Reduction in trunk flexion during
      ambulation has been shown to improve gait parameters for reciprocating gait
      orthosis users. OBJECTIVE: The aim of this study was to investigate the effect on
      energy expenditure when spinal cord injury patients ambulate with an advanced
      reciprocating gait orthosis while wearing a thoracolumbosacral orthosis to
      provide trunk extension. STUDY DESIGN: Quasi experimental study. METHODS: Four
      patients with spinal cord injury were fitted with an advanced reciprocating gait
      orthosis after completing a specific gait training program. Patients walked along
      a flat walkway using the advanced reciprocating gait orthosis as a control
      condition and also while additionally wearing a thoracolumbosacral orthosis at
      their self-selected walking speed. A stopwatch and a polar heart rate monitor
      were used to measure walking speed and heart rate. RESULTS: Walking speed, the
      distance walked, and the physiological cost index all improved when walking with
      the advanced reciprocating gait orthosis/thoracolumbosacral orthosis test
      condition compared to walking with no thoracolumbosacral orthosis in situ.
      CONCLUSION: Spinal cord injury patients can improve their walking speed, walking
      distance, and physiological cost index when wearing a thoracolumbosacral orthosis
      in conjunction with an advanced reciprocating gait orthosis, which may be
      attributed to the trunk extension provided by the thoracolumbosacral orthosis.
      CLINICAL RELEVANCE: It is concluded that wearing thoracolumbosacral orthosis in
      association with an advanced reciprocating gait orthosis could be an effective
      alternative in rehabilitation for thoracic level of paraplegic patients to
      promote their health and well-being.

PMID- 26209423
TI  - The effects of a concurrent task on walking in persons with transfemoral
      amputation compared to persons without limb loss.
AB  - BACKGROUND: Many people with lower limb loss report the need to concentrate on
      walking. This may indicate increased reliance on cognitive resources when walking
      compared to individuals without limb loss. OBJECTIVE: This study quantified
      changes in walking associated with addition of a concurrent cognitive task in
      persons with transfemoral amputation using microprocessor knees compared to age-
      and sex-matched controls. STUDY DESIGN: Observational, cross-sectional study.
      METHODS: Quantitative motion analysis was used to assess walking under both
      single-task (walking alone) and dual-task (walking while performing a cognitive
      task) conditions. Primary outcomes were walking speed, step width, step time
      asymmetry, and cognitive task response latency and accuracy. Repeated-measures
      analysis of variance was used to examine the effects of task (single-task and
      dual-task) and group (transfemoral amputation and control) for each outcome.
      RESULTS: No significant interactions between task and group were observed (all p
      > 0.11) indicating that a cognitive task did not differentially affect walking
      between groups. However, walking was slower with wider steps and more asymmetry
      in people with transfemoral amputation compared to controls under both
      conditions. CONCLUSION: Although there were significant differences in walking
      between people with transfemoral amputation and matched controls, the effects of
      a concurrent cognitive task on walking were similar between groups. CLINICAL
      RELEVANCE: The addition of a concurrent task did not differentially affect
      walking outcomes in people with and without transfemoral amputation. However,
      compared to people without limb loss, people with transfemoral amputation adopted
      a conservative walking strategy. This strategy may reduce the need to concentrate
      on walking but also contributed to notable gait deviations.

PMID- 26209424
TI  - Passive-dynamic ankle-foot orthosis replicates soleus but not gastrocnemius
      muscle function during stance in gait: Insights for orthosis prescription.
AB  - BACKGROUND: Passive-dynamic ankle-foot orthosis characteristics, including
      bending stiffness, should be customized for individuals. However, while
      conventions for customizing passive-dynamic ankle-foot orthosis characteristics
      are often described and implemented in clinical practice, there is little
      evidence to explain their biomechanical rationale. OBJECTIVES: To develop and
      combine a model of a customized passive-dynamic ankle-foot orthosis with a
      healthy musculoskeletal model and use simulation tools to explore the influence
      of passive-dynamic ankle-foot orthosis bending stiffness on plantar flexor
      function during gait. STUDY DESIGN: Dual case study. METHODS: The customized
      passive-dynamic ankle-foot orthosis characteristics were integrated into a
      healthy musculoskeletal model available in OpenSim. Quasi-static forward dynamic
      simulations tracked experimental gait data under several passive-dynamic ankle
      foot orthosis conditions. Predicted muscle activations were calculated through a
      computed muscle control optimization scheme. RESULTS: Simulations predicted that
      the passive-dynamic ankle-foot orthoses substituted for soleus but not
      gastrocnemius function. Induced acceleration analyses revealed the passive
      dynamic ankle-foot orthosis acts like a uniarticular plantar flexor by inducing
      knee extension accelerations, which are counterproductive to natural knee
      kinematics in early midstance. CONCLUSION: These passive-dynamic ankle-foot
      orthoses can provide plantar flexion moments during mid and late stance to
      supplement insufficient plantar flexor strength. However, the passive-dynamic
      ankle-foot orthoses negatively influenced knee kinematics in early midstance.
      CLINICAL RELEVANCE: Identifying the role of passive-dynamic ankle-foot orthosis
      stiffness during gait provides biomechanical rationale for how to customize
      passive-dynamic ankle-foot orthoses for patients. Furthermore, these findings can
      be used in the future as the basis for developing objective prescription models
      to help drive the customization of passive-dynamic ankle-foot orthosis
      characteristics.

PMID- 26209425
TI  - Foot deformities within the diabetic foot and their influence on biomechanics: A
      review of the literature.
AB  - BACKGROUND: Diabetes mellitus causes a multitude of complications. Foot
      ulceration is one complication with serious consequences, amputation. Foot
      deformities contribute to ulcer development. It would be advantageous to
      ascertain whether foot deformities are preventable as their presence increases
      amputation risk. OBJECTIVES: The objectives were to understand the development of
      foot deformities in diabetes and explore their biomechanical effects. STUDY
      DESIGN: Literature review. METHODS: In February 2014 CINAHL, Embase, Ovid and
      Medline were searched. Studies in English of adults with Diabetes that reported
      neuropathy, foot deformities or associated gait abnormalities were included for
      review. All study designs were considered. The articles' quality was considered
      high overall, assessed using SIGN and CARS. RESULTS: In total, 17 studies were
      reviewed. The main themes identified in relation to foot deformities were nerve
      function, intrinsic foot muscles, muscle weakness and limited joint mobility.
      Nerve function and intrinsic foot muscle atrophy did not display definitive
      associations with foot deformities. However, muscle weakness and limited joint
      mobility were associated with foot deformities, although the relationship is
      still unclear. CONCLUSION: The development of common foot deformities in diabetes
      is not well understood. The literature did not support the common belief that
      motor neuropathy, atrophy and muscle imbalance cause foot deformities. CLINICAL
      RELEVANCE: An understanding of the aetiology of foot deformities in diabetes
      mellitus may allow for pro-active management of the foot in anticipation of the
      development of foot deformities and ulceration. If the aetiology of deformity was
      established preventative treatment may reduce the incidence of foot deformities
      and resultant ulcerations and amputations.

PMID- 26209426
TI  - Can the natural turf pitch be viewed as a risk factor for injury within
      Association Football?
AB  - OBJECTIVES: A review of the current literature is used to propose a 'conceptual
      model for relative pitch hardness' and how this may affect incidence of injury
      within Association Football. Based upon the injury risk and causation model of
      Meeuwisse et al. (Clin J Sport Med 2007; 17(3):215), it may provide researchers a
      necessary framework to guide future research investigations. DESIGN: A literature
      review. METHODS: A comprehensive search of electronic databases available until
      October 2014, and supplemental hand searching was conducted to identify relevant
      studies. Studies were deemed relevant if they met the following criteria:
      published in English, presented or referenced in an epidemiological study or
      provided data directly and/or related to the surface of the football pitch, ball
      or boot to surface interaction and injury. Further information was sourced on
      surface hardness, players' movement patterns and physiological demands within
      football. RESULTS: Papers varied in methodological quality, with comparative
      studies examining injury rates on artificial versus natural turf pitches being
      most prevalent. No prospective studies were found that objectively measured the
      relationship between hardness of natural turf and injury risk within football.
      CONCLUSIONS: The literature review into natural turf pitches and injury within
      football has largely been unable to confirm that pitch hardness can be viewed as
      a significant extrinsic risk factor. Methodological concerns, including
      objectivity in pitch assessment and uniformity in defining injuries undermine the
      efficacy of available work. Future studies are needed utilising objective
      assessment tools to draw more definitive conclusions regarding pitch hardness as
      an extrinsic factor for injury within football.

PMID- 26209427
TI  - Monitoring athletic training status using the maximal rate of heart rate
      increase.
AB  - OBJECTIVES: Reductions in maximal rate of heart rate increase (rHRI) correlate
      with performance reductions when training load is increased. This study evaluated
      whether rHRI tracked performance changes across a range of training states.
      DESIGN: Prospective intervention. METHODS: rHRI was assessed during five min of
      cycling at 100W (rHRIcyc) and running at 8km/h (rHRIrun) in 13 male triathletes
      following two weeks of light-training (LT), two weeks of heavy-training (HT) and
      a two-day recovery period (RP). A five min cycling time-trial assessed
      performance and peak oxygen consumption (VO2peak). RESULTS: Performance likely
      decreased following HT (Effect size+/-90% confidence interval=-0.18+/-0.09), then
      very likely increased following RP (0.32+/-0.14). rHRIcyc very likely decreased (
      0.48+/-0.24), and rHRIrun possibly decreased (-0.33+/-0.48), following HT.
      Changes in both measures were unclear following RP. Steady-state HR was almost
      certainly lower (-0.81+/-0.31) during rHRIcyc than rHRIrun. A large correlation
      was found between reductions in performance and rHRIrun (r+/-90%; CI=0.65+/-0.34)
      from LT to HT, but was unclear for rHRIcyc. Trivial within-subject correlations
      were found between rHRI and performance, but the strength of relationship between
      rHRIrun and performance was largely associated with VO2peak following LT (r=
      0.58+/-0.38). CONCLUSIONS: Performance reductions were most sensitively tracked
      by rHRIrun following HT. This may be due to rHRIrun being assessed at a higher
      intensity than rHRIcyc, inferred from a higher steady-state HR and supported by a
      stronger within-subject relationship between rHRIrun and performance in
      individuals with a lower VO2peak, in whom the same exercise intensity would
      represent a greater physiological stress. rHRI assessed at relatively high
      exercise intensities may better track performance changes.

PMID- 26209428
TI  - Patterns of treatment and correction of hyponatremia in intensive care unit
      patients.
AB  - PURPOSE: The goal of this study was to examine the real-world patterns of care
      and interventions among intensive care unit (ICU) patients with hypervolemic and
      euvolemic hyponatremia using a large clinical database. MATERIALS AND METHODS:
      The Phillips eICU Research Institute database was used to investigate
      hyponatremia treatment patterns and trends, mortality, and ICU and hospital
      length of stay. Demographics, clinical characteristics, and outcome variables
      were compared in patients corrected for hyponatremia using both a more strict and
      a less strict definition. RESULTS: At admission, 35%, 55%, and 10% of patients
      had mild, moderate, and severe hyponatremia, respectively. At the end of an ICU
      stay, the percentage of patients who did not have corrected serum sodium
      concentration was 48% (using a more strict definition) and 24% (using a less
      strict definition). Using either definition of correction, patients with serum
      sodium correction had lower mortality and longer survival than did patients
      without corrected serum sodium concentration. CONCLUSIONS: A significant
      proportion of hyponatremia is not corrected during an ICU stay. Critically ill
      patients with hyponatremia who have their serum sodium corrected have lower
      mortality and longer survival, highlighting the need for more attention to
      hyponatremia and its correction in critically ill patients.

PMID- 26209429
TI  - Alternative preprocessing of RNA-Sequencing data in The Cancer Genome Atlas leads
      to improved analysis results.
AB  - MOTIVATION: The Cancer Genome Atlas (TCGA) RNA-Sequencing data are used widely
      for research. TCGA provides 'Level 3' data, which have been processed using a
      pipeline specific to that resource. However, we have found using experimentally
      derived data that this pipeline produces gene-expression values that vary
      considerably across biological replicates. In addition, some RNA-Sequencing
      analysis tools require integer-based read counts, which are not provided with the
      Level 3 data. As an alternative, we have reprocessed the data for 9264 tumor and
      741 normal samples across 24 cancer types using the Rsubread package. We have
      also collated corresponding clinical data for these samples. We provide these
      data as a community resource. RESULTS: We compared TCGA samples processed using
      either pipeline and found that the Rsubread pipeline produced fewer zero
      expression genes and more consistent expression levels across replicate samples
      than the TCGA pipeline. Additionally, we used a genomic-signature approach to
      estimate HER2 (ERBB2) activation status for 662 breast-tumor samples and found
      that the Rsubread data resulted in stronger predictions of HER2 pathway activity.
      Finally, we used data from both pipelines to classify 575 lung cancer samples
      based on histological type. This analysis identified various non-coding RNA that
      may influence lung-cancer histology. AVAILABILITY AND IMPLEMENTATION: The RNA
      Sequencing and clinical data can be downloaded from Gene Expression Omnibus
      (accession number GSE62944). Scripts and code that were used to process and
      analyze the data are available from
      https://github.com/srp33/TCGA_RNASeq_Clinical. CONTACT: stephen_piccolo@byu.edu
      or andreab@genetics.utah.edu SUPPLEMENTARY INFORMATION: Supplementary material is
      available at Bioinformatics online.

PMID- 26209430
TI  - CRISPR-ERA: a comprehensive design tool for CRISPR-mediated gene editing,
      repression and activation.
AB  - The CRISPR/Cas9 system was recently developed as a powerful and flexible
      technology for targeted genome engineering, including genome editing (altering
      the genetic sequence) and gene regulation (without altering the genetic
      sequence). These applications require the design of single guide RNAs (sgRNAs)
      that are efficient and specific. However, this remains challenging, as it
      requires the consideration of many criteria. Several sgRNA design tools have been
      developed for gene editing, but currently there is no tool for the design of
      sgRNAs for gene regulation. With accumulating experimental data on the use of
      CRISPR/Cas9 for gene editing and regulation, we implement a comprehensive
      computational tool based on a set of sgRNA design rules summarized from these
      published reports. We report a genome-wide sgRNA design tool and provide an
      online website for predicting sgRNAs that are efficient and specific. We name the
      tool CRISPR-ERA, for clustered regularly interspaced short palindromic repeat
      mediated editing, repression, and activation (ERA). AVAILABILITY AND
      IMPLEMENTATION: http://CRISPR-ERA.stanford.edu. CONTACT: stanley.qi@stanford.edu
      or xwwang@tsinghua.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 26209431
TI  - dendextend: an R package for visualizing, adjusting and comparing trees of
      hierarchical clustering.
AB  - dendextend is an R package for creating and comparing visually appealing tree
      diagrams. dendextend provides utility functions for manipulating dendrogram
      objects (their color, shape and content) as well as several advanced methods for
      comparing trees to one another (both statistically and visually). As such,
      dendextend offers a flexible framework for enhancing R's rich ecosystem of
      packages for performing hierarchical clustering of items. AVAILABILITY AND
      IMPLEMENTATION: The dendextend R package (including detailed introductory
      vignettes) is available under the GPL-2 Open Source license and is freely
      available to download from CRAN at: (http://cran.r
      project.org/package=dendextend) CONTACT: Tal.Galili@math.tau.ac.il.

PMID- 26209432
TI  - A mutation profile for top-k patient search exploiting Gene-Ontology and
      orthogonal non-negative matrix factorization.
AB  - MOTIVATION: As the quantity of genomic mutation data increases, the likelihood of
      finding patients with similar genomic profiles, for various disease inferences,
      increases. However, so does the difficulty in identifying them. Similarity search
      based on patient mutation profiles can solve various translational bioinformatics
      tasks, including prognostics and treatment efficacy predictions for better
      clinical decision making through large volume of data. However, this is a
      challenging problem due to heterogeneous and sparse characteristics of the
      mutation data as well as their high dimensionality. RESULTS: To solve this
      problem we introduce a compact representation and search strategy based on Gene
      Ontology and orthogonal non-negative matrix factorization. Statistical
      significance between the identified cancer subtypes and their clinical features
      are computed for validation; results show that our method can identify and
      characterize clinically meaningful tumor subtypes comparable or better in most
      datasets than the recently introduced Network-Based Stratification method while
      enabling real-time search. To the best of our knowledge, this is the first
      attempt to simultaneously characterize and represent somatic mutational data for
      efficient search purposes. AVAILABILITY: The implementations are available at:
      https://sites.google.com/site/postechdm/research/implementation/orgos. CONTACT:
      sael@cs.stonybrook.edu or hwanjoyu@postech.ac.kr SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 26209434
TI  - Startle responding in the context of visceral pain.
AB  - This study aimed to investigate affective modulation of eye blink startle by
      aversive visceral stimulation. Startle blink EMG responses were measured in 31
      healthy participants receiving painful, intermittent balloon distentions in the
      distal esophagus during 4 blocks (positive, negative, neutral or no pictures),
      and compared with startles during 3 'safe' blocks without esophageal stimulations
      (positive, negative or neutral emotional pictures). Women showed enhanced startle
      during blocks with distentions (as compared with 'safe' blocks), both when the
      balloon was in inflated and deflated states, suggesting that fear and/or
      expectations may have played a role. Men's startle did not differ between
      distention and non-distention blocks. In this particular study context affective
      picture viewing did not further impose any effect on startle eye blink responses.
      The current results may contribute to a better understanding of emotional
      reactions to aversive interoceptive stimulation. 

PMID- 26209433
TI  - GeneVetter: a web tool for quantitative monogenic assessment of rare diseases.
AB  - When performing DNA sequencing to diagnose affected individuals with monogenic
      forms of rare diseases, accurate attribution of causality to detected variants is
      imperative but imperfect. Even if a gene has variants already known to cause a
      disease, rare disruptive variants predicted to be causal are not always so,
      mainly due to imperfect ability to predict the pathogenicity of variants.
      Existing population-scale sequence resources such as 1000 Genomes are useful to
      quantify the 'background prevalence' of an unaffected individual being falsely
      predicted to carry causal variants. We developed GeneVetter to allow users to
      quantify the 'background prevalence' of subjects with predicted causal variants
      within specific genes under user-specified filtering parameters. GeneVetter helps
      quantify uncertainty in monogenic diagnosis and design genetic studies with
      support for power and sample size calculations for specific genes with specific
      filtering criteria. GeneVetter also allows users to analyze their own sequence
      data without sending genotype information over the Internet. Overall, GeneVetter
      is an interactive web tool that facilitates quantifying and accounting for the
      background prevalence of predicted pathogenic variants in a population.
      AVAILABILITY AND IMPLEMENTATION: GeneVetter is available at
      http://genevetter.org/ CONTACT: mgsamps@med.umich.edu or hmkang@umich.edu
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 26209435
TI  - Evaluating the engagement of universities in capacity building for sustainable
      development in local communities.
AB  - Universities have the potential to play a leading role in enabling communities to
      develop more sustainable ways of living and working however, sustainable
      communities may only emerge with facilitation, community learning and continual
      efforts to build their capacities. Elements of programme planning and evaluation
      on the one hand, and capacity building on the other, are needed. The latter
      entails approaches and processes that may contribute to community empowerment;
      universities may either lead such approaches, or be key partners in an endeavour
      to empower communities to address the challenges posed by the need for
      sustainable development. Although capacity building and the promotion of
      sustainable development locally, are on the agenda for universities who take
      seriously regional engagement, very little is published that illustrates or
      describes the various forms of activities that take place. Further, there is a
      paucity of studies that have evaluated the work performed by universities in
      building capacity for sustainable development at the local level. This paper is
      an attempt to address this need, and entails an empirical study based on a sample
      of universities in the United Kingdom, Germany, Portugal and Brazil. The paper
      examines the extent to which capacity building for sustainable development is
      being undertaken, suggests the forms that this might take and evaluates some of
      the benefits for local communities. The paper concludes by reinforcing that
      universities have a critical role to play in community development; that role has
      to prioritise the sustainability agenda. 

PMID- 26209436
TI  - Use of data mining at the Food and Drug Administration.
AB  - OBJECTIVES: This article summarizes past and current data mining activities at
      the United States Food and Drug Administration (FDA). TARGET AUDIENCE: We address
      data miners in all sectors, anyone interested in the safety of products regulated
      by the FDA (predominantly medical products, food, veterinary products and
      nutrition, and tobacco products), and those interested in FDA activities. SCOPE:
      Topics include routine and developmental data mining activities, short
      descriptions of mined FDA data, advantages and challenges of data mining at the
      FDA, and future directions of data mining at the FDA.

PMID- 26209437
TI  - Hepatoprotective effect of mulberry (Morus nigra) leaves extract against
      methotrexate induced hepatotoxicity in male albino rat.
AB  - BACKGROUND: Drug-induced liver injury is a major health problem that challenges
      not only health care professionals but also the pharmaceutical industry and drug
      regulatory agencies. The possible hepatoprotective effect of the administration
      of mulberry ethanolic extract (MUL) leaves against hepatotoxic effect of the anti
      rheumatic drug, methotrexate (MTX) was evaluated in this study both vivo (using
      animal models) and in vitro (human hepatoma HepG2 cells). METHODS: In the in-vivo
      study, 20 male albino rats were equally assigned into four groups; control group
      received distilled water orally; MUL treated-group received 500 mg/kg/day of MUL
      extract; MTX treated-group was injected with a single dose of 20 mg/kg MTX
      intraperitoneally on the 4th day; MUL-MTX treated-group received the previously
      mentioned doses of MUL and MTX (both control and MUL treated groups were
      administered a single dose of a physiological saline i.p.). At the end of the
      experimental period (14 days) activities of alanine transaminase (ALT), aspartate
      transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) as
      well as total serum protein (TP) and albumin (ALB) levels were evaluated to
      assess liver function. RESULTS: A marked reduction in the viability of HepG2
      cells was observed after 48 h with IC50 equal to 14.5 MUg/mL of MUL
      administration. Treating the animals with MUL in combination with MTX mitigated
      liver injury, causing a significant reduction in activities of AST, ALT, ALP and
      LDH as compared to the MTX-group. The liver architecture revealed more or less
      normal appearance with the combined treatment when compared with MTX treatment
      alone. CONCLUSIONS: This study recommends that the co-administration of MUL with
      MTX that may have therapeutic benefits against MTX-hepato-cytotoxicity.

PMID- 26209438
TI  - Elevated C1orf63 expression is correlated with CDK10 and predicts better outcome
      for advanced breast cancers: a retrospective study.
AB  - BACKGROUND: Chromosome 1 open reading frame 63 (C1orf63) is located on the distal
      short arm of chromosome 1, whose allelic loss has been observed in several human
      cancers. C1orf63 has been reported to be up-regulated in IL-2-starved T
      lymphocytes, which suggests it might be involved in cell cycle control, a common
      mechanism for carcinogenesis. Here we investigated the expression and clinical
      implication of C1orf63 in breast cancer. METHODS: Paraffin-embedded specimens,
      clinicopathological features and follow-up data of the breast cancer patients
      were collected. Publicly available microarray and RNA-seq datasets used in this
      study were downloaded from ArrayExpress of EBI and GEO of NCBI. KM plotter tool
      was also adopted. The expression of C1orf63 and CDK10, one known cell cycle
      dependent tumor suppressor in breast cancer, was assessed by
      immunohistochemistry. Western blotting was performed to detect C1orf63 protein in
      human breast cancer cell lines, purchased from the Culture Collection of the
      Chinese Academy of Sciences, Shanghai. RESULTS: In a group of 12 human breast
      tumors and their matched adjacent non-cancerous tissues, C1orf63 expression was
      observed in 7 of the 12 breast tumors, but not in the 12 adjacent non-cancerous
      tissues (P < 0.001). Similar results were observed of C1orf63 mRNA expression
      both in breast cancer and several other cancers, including lung cancer, prostate
      cancer and hepatocellular carcinoma. In another group of 182 breast cancer
      patients, C1orf63 expression in tumors was not correlated with any
      clinicopathological features collected in this study. Survival analyses showed
      that there was no significant difference of overall survival (OS) rates between
      the C1orf63 (+) group and the C1orf63 (-) group (P = 0.145). However, the
      analyses of KM plotter displayed a valid relationship between C1orf63 and RFS
      (relapse free survival)/OS (P < 0.001; P = 0.007). Notablely, in breast cancers
      with advanced TNM stages (III ~ IV) among these 182 patients, C1orf63 expression
      was an independent prognostic factor predicting better clinical outcome (HR:
      0.41; 95 % CI: 0.17 ~ 0.97; P = 0.042). Additionally, we found that CDK10 mRNA
      expression was positively correlated with C1orf63, which was consistent with the
      relationship of protein expression between C1orf63 and CDK10 (r s = 0.391; P <
      0.001). CONCLUSIONS: Compared to adjacent non-cancerous tissues, C1orf63
      expression was elevated in tumor tissues. However, C1orf63 predicts better
      prognosis for breast cancers with advanced TNM stage, and the underlying
      mechanism is unknown. In addition, C1orf63 is correlated with the cell cycle
      related gene, CDK10.

PMID- 26209439
TI  - Change in motor function and adverse health outcomes in older African-Americans.
AB  - OBJECTIVE: We tested whether declining motor function accelerates with age in
      older African-Americans. METHODS: Eleven motor performances were assessed
      annually in 513 older African-Americans. RESULTS: During follow-up of 5 years,
      linear mixed-effect models showed that motor function declined by about 0.03
      units/year (Estimate, -0.026, p<0.001); about 4% more rapidly for each additional
      year of age at baseline. A proportional hazard model showed that both baseline
      motor function level and its rate of change were independent predictors of death
      and incident disability (all p's<0.001). These models showed that the additional
      annual amount of motor decline in 85 year old persons at baseline versus 65 year
      old persons was associated with a 1.5-fold higher rate of death and a 3-fold
      higher rate of developing Katz disability. CONCLUSIONS: The rate of declining
      motor function accelerates with increasing age and its rate of decline predicts
      adverse health outcomes in older African-Americans.

PMID- 26209440
TI  - Comparison of clinical course and outcome of acute pancreatitis according to the
      two main etiologies: alcohol and gallstone.
AB  - BACKGROUND: Studies concerning clinical course and outcome of acute pancreatitis
      (AP) according to etiologies were rare, especially after year 2000. This study
      was designed to investigate the difference between the clinical course of
      alcoholic and biliary AP. METHODS: Of the 153 patients diagnosed as AP with a
      first attack between January 2011 and January 2013, extensive clinical data of 50
      patients with AP caused by alcohol and 76 patients with AP caused by gallstone
      were analyzed retrospectively. We compared the severity of AP defined by revised
      Atlanta classification in 2012, local complications, severity scores, and
      computed tomography severity index (CTSI) between alcoholic and biliary AP. We
      also evaluated the length of hospital stay, duration of NPO, and in-hospital
      mortality in each group. RESULTS: Hemoglobin, hematocrit, and serum C-reactive
      protein level measured after admission for 24 h were significantly higher in the
      alcohol group than in the biliary group. Incidence of pseudocyst formation was
      significantly higher in the alcohol group than in the biliary group (20.0 % vs.
      6.6 %, P = 0.023). Among prognostic scoring systems, only CTSI showed significant
      difference (P < 0.001) with a mean score of 3.0 +/- 0.9 in the alcohol group and
      1.7 +/- 1.2 in the biliary group. Severe AP with organ failure persisting beyond
      48 h was observed in 12 patients (24.0 %) in the alcohol group and one patient
      (1.3 %) in the biliary group (P < 0.001). There were 4 mortalities in the alcohol
      group only (P = 0.012). CONCLUSION: More severe forms of AP and local
      complication, such as pseudocyst formation, are associated with alcoholic AP
      compared with biliary AP.

PMID- 26209441
TI  - Complete genome sequence of Ostreid herpesvirus-1 associated with mortalities of
      Scapharca broughtonii broodstocks.
AB  - BACKGROUND: Ostreid herpesvirus-1 (OsHV-1) is the major bivalve pathogen
      associated with severe mortality events in a wide host range. In the early summer
      of 2012 and 2013, mass mortalities of blood clam (Scapharca broughtonii)
      broodstocks associated with a newly described variant of OsHV-1 (OsHV-1-SB) were
      reported. METHODS: In this study, the complete genome sequence of the newly
      described variant was determined through the primer walking approach, and
      compared with those of the other two OsHV-1 variants. RESULTS: OsHV-1-SB genome
      was found to contain 199, 354 bp nucleotides with 38.5% G/C content, which is
      highly similar to those of acute viral necrosis virus (AVNV) and OsHV-1 reference
      type. A total of 123 open reading frames (ORFs) putatively encoding functional
      proteins were identified; eight of which were duplicated in the major repeat
      elements of the genome. The genomic organization of OsHV-1-SB could be
      represented as TRL-UL-IRL-IRS-US-TRS, which is different from that of OsHV-1
      reference type and AVNV due to the deletion of a unique region (X, 1.5Kb) between
      IRL and IRS. The DNA sequence of OsHV-1-SB is 95.2% and 97.3% identical to that
      of OsHV-1 reference type and AVNV respectively. On the basis of nucleotide
      sequences of 32 ORFs in OsHV-1-SB and the other nine OsHV-1 variants, results
      from phylogenetic analysis also demonstrated that OsHV-1-SB is most closely
      related to AVNV. CONCLUSIONS: The determination of the genome of OsHV-1 with
      distinguished epidemiological features will aid in our better understanding of
      OsHV-1 diversity, and facilitate further research on the origin, evolution, and
      epidemiology of the virus.

PMID- 26209443
TI  - Ability of esCCO to track changes in cardiac output.
AB  - BACKGROUND: We investigated whether cardiac output measured with pulse wave
      transit time (esCCO, Nihon Kohden, Tokyo, Japan) is able to track changes in
      cardiac output induced by an increase in preload (volume expansion/passive leg
      raising) or by changes in vasomotor tone (variation in norepinephrine dosage) in
      critically ill patients. METHODS: Eighty patients for whom the decision to give
      fluid (500 mL of saline over 15 min) (n=20), to perform passive leg-raising
      (n=20), and to increase (n=20) or to decrease (n=20) norepinephrine were included
      by the physician. Cardiac output was measured with pulse wave transit time (CO
      esCCO) and transthoracic echocardiography (CO-TTE) before and after therapeutic
      intervention. RESULTS: Comparison between CO-TTE and CO-esCCO showed a bias of 
      0.7 l min(-1) and limits of agreement of -4.4 to 2.9 l min(-1), before
      therapeutic intervention and a bias of -0.5 l min(-1) and limits of agreement of 
      4.2 to 3.2 l min(-1) after therapeutic intervention. Bias was correlated with
      systemic vascular resistance (r(2)=0.60, P<0.0001). Percentage error was 61%
      before and 59% after therapeutic intervention. Considering the overall data
      (n=80), the concordance rate was 84%, polar plot analysis revealed an angular
      bias (sd) of -11 degrees (35 degrees ) and radial limits of agreement of (sd 50
      degrees ). With regard to passive leg-raising and volume expansion groups (n=40),
      the concordance rate was 83%, the angular bias (sd) was -20 degrees (36 degrees )
      and radial limits of agreement ( 50 degrees ). Considering variations in
      norepinephrine dosage groups (n=40), the concordance rate was 86%, the angular
      bias (sd) was -1.8 degrees (33 degrees ) and radial limits of agreement (40
      degrees ). CONCLUSIONS: esCCO was not able to track changes in cardiac output,
      induced by an increase in preload or by variations in vasomotor tone. Therefore,
      esCCO cannot guide haemodynamic interventions in critically ill patients.

PMID- 26209442
TI  - Autoregulatory function of interleukin-10-producing pre-naive B cells is
      defective in systemic lupus erythematosus.
AB  - INTRODUCTION: Pre-naive B cells represent an intermediate stage in human B-cell
      development with some functions of mature cells, but their involvement in immune
      responses is unknown. The aim of this study was to determine the functional role
      of normal pre-naive B cells during immune responses and possible abnormalities in
      systemic lupus erythematosus (SLE) that might contribute to disease pathogenesis.
      METHODS: Pre-naive, naive, and memory B cells from healthy individuals and SLE
      patients were stimulated through CD40 and were analyzed for interleukin-10 (IL
      10) production and co-stimulatory molecule expression and their regulation of T
      cell activation. Autoreactivity of antibodies produced by pre-naive B cells was
      tested by measuring immunoglobulin M (IgM) autoantibodies in culture supernatants
      after differentiation. RESULTS: CD40-stimulated pre-naive B cells produce larger
      amounts of IL-10 but did not suppress CD4(+) T-cell cytokine production.
      Activated pre-naive B cells demonstrated IL-10-mediated ineffective promotion of
      CD4(+) T-cell proliferation and induction of CD4(+)FoxP3(+) T cells and IL-10
      independent impairment of co-stimulatory molecule expression and tumor necrosis
      factor-alpha (TNF-alpha) and IL-6 production. IgM antibodies produced by
      differentiated pre-naive B cells were reactive to single-stranded
      deoxyribonucleic acid. SLE pre-naive B cells were defective in producing IL-10,
      and co-stimulatory molecule expression was enhanced, resulting in promotion of
      robust CD4(+) T-cell proliferation. CONCLUSIONS: There is an inherent and IL-10
      mediated mechanism that limits the capacity of normal pre-naive B cells from
      participating in cellular immune response, but these cells can differentiate into
      autoantibody-secreting plasma cells. In SLE, defects in IL-10 secretion permit
      pre-naive B cells to promote CD4(+) T-cell activation and may thereby enhance the
      development of autoimmunity.

PMID- 26209444
TI  - The role of diagnostic ureteroscopy in the era of computed tomography urography.
AB  - BACKGROUND: To examine the contemporary role of ureteroscopy in the diagnosis of
      upper urinary tract urothelial carcinoma. METHODS: We retrospectively evaluated
      116 diagnostic ureteroscopies, performed in our institution to rule out primary
      UTUC. Demographics, cytological findings and interpretation of preoperative
      imaging were obtained. Ureteroscopic diagnosis and histological results were
      recorded and the predictive values of diagnostic studies were determined. Follow
      up data was reviewed to evaluate the oncological outcomes in patients treated
      endoscopically. RESULTS: The pre-ureteroscopic evaluation included CTU in 91
      (78%) patients. Positive and Negative predictive values of CTU were 76 and 80%,
      respectively. Typical filling defect on CTU was demonstrated in 38 of 89
      patients. UTUC has been ruled out in 9 patients (24%) with suspicious filling
      defect on CTU. Endoscopic approach was implemented in 7 patients (18%). During a
      median follow up period of 17 months (IQR, 9-25) none of the followed patients
      experienced disease progression. CONCLUSIONS: Nephroureterectomy was spared from
      42% of patients who underwent diagnostic ureteroscopy for suspected UTUC,
      demonstrated on CTU. In about half of those patients tumor has been ruled out and
      the others were managed endoscopically. Therefore, diagnostic ureteroscopy is
      advised as a crucial step in confirming UTUC and treatment planning.

PMID- 26209445
TI  - Therapeutic effect of polysaccharide fraction of Atractylodis macrocephalae
      Koidz. in bovine subclinical mastitis.
AB  - BACKGROUND: Mastitis is considered the most significant and persistent disease in
      dairy cows, bringing about large economic losses. Subclinical mastitis brings
      about major cost implications, for it is difficult to detect due to absence of
      any visible indications and can persist in the mammary tissue throughout
      lactation. Immunomodulators have been widely used to reduce intramammary
      infections by modulating bovine mammary gland. Atractylodis macrocephalae Koidz.
      polysaccharides (RAMP), extracted from herbal medicine, has been used widely
      especially for its immunomodulatory function for many years. The objective of
      this study was to estimate an oil emulsified Atractylodis macrocephalae Koidz.
      polysaccharides (RAMP-O) as a potential therapeutic agent to treat subclinical
      mastitis by subcutaneous injection of RAMP-O in the area of supramammary lymph
      node in lactating cows via analysis of SCC, IMIs and NAGase. RESULTS: Injection
      of RAMP-O in the area of supramammary lymph node significantly reduced milk SCC
      and NAGase activity compared with control. The quarters with bacterial infection
      were also progressively reduced in RAMP-O treated cows and only 9 quarters were
      found to have bacterial infection, while no obvious change was found in the
      control group. CONCLUSIONS: Subcutaneous injection of RAMP-O in the area of
      supramammary lymph node had therapeutic value in the treatment of bovine
      subclinical mastitis by reducing SCC, NAGase and IMIs in milk. Considering both
      the therapeutic effect and the cost of RAMP-O, 32 mg per dose was found most
      suitable to reduce milk SCC and NAGase. Therefore, RAMP-O deserves further study
      for its use in treatment of bovine mastitis.

PMID- 26209446
TI  - Determining optimal planning target volume and image guidance policy for post
      prostatectomy intensity modulated radiotherapy.
AB  - BACKGROUND: There is limited information available on the optimal Planning Target
      Volume (PTV) expansions and image guidance for post-prostatectomy intensity
      modulated radiotherapy (PP-IMRT). As the prostate bed does not move in a uniform
      manner, there is a rationale for anisotropic PTV margins with matching to soft
      tissue. The aim of this study is to find the combination of PTV expansion and
      image guidance policy for PP-IMRT that provides the best balance of target
      coverage whilst minimising dose to the organs at risk. METHODS: The Cone Beam CT
      (CBCT) images (n = 377) of 40 patients who received PP-IMRT with daily online
      alignment to bony anatomy (BA) were reviewed. Six different PTV expansions were
      assessed: 3 published PTV expansions (0.5 cm uniform, 1 cm uniform, and 1 + 0.5
      cm posterior) and 3 further anisotropic PTV expansions (Northern Sydney Cancer
      Centre (NSCC), van Herk, and smaller anisotropic). Each was assessed for size,
      bladder and rectum coverage and geographic miss. Each CBCT was rematched using a
      superior soft tissue (SST) and averaged soft tissue (AST) match. Potential
      geographic miss was assessed using all PTV expansions except the van Herk margin.
      RESULTS: The 0.5 cm uniform expansion yielded the smallest PTV (median volume =
      222.3 cc) and the 1 cm uniform expansion yielded the largest (361.7 cc). The Van
      Herk expansion includes the largest amount of bladder (28.0 %) and rectum (36.0
      %) and the 0.5 cm uniform expansion the smallest (17.1 % bladder; 10.2 % rectum).
      The van Herk PTV expansion had the least geographic miss with BA matching (4.2 %)
      and the 0.5 cm uniform margin (28.4 %) the greatest. BA matching resulted in the
      highest geographic miss rate for all PTVs, followed by SST matching and AST
      matching. Changing from BA to an AST match decreases potential geographic miss by
      half to two thirds, depending on the PTV expansion, to <10 % for all PTV
      expansions. When using the smaller anisotropic PTV expansion, AST matching would
      reduce the geographic miss rate from 21.0 % with BA matching down to 5.6 %.
      CONCLUSIONS: Our results suggest the optimal PTV expansion and image guidance
      policy for PP-IMRT is daily average soft tissue matching using CBCT scans with a
      small anisotropic PTV expansion of 0.5 cm in all directions apart from a 1 cm
      expansion in the anterior-posterior direction in the upper prostate bed. Care
      must be taken to ensure adequate training of Radiation Therapists to perform soft
      tissue matching with CBCT scans.

PMID- 26209448
TI  - Reading Efficiency of Deaf and Hearing People in Spanish.
AB  - Different studies have showed poor reading performance in the deaf compared to
      the hearing population. This has overshadowed the fact that a minority of deaf
      children learns to read successfully and reaches levels similar to their hearing
      peers. We analyze whether deaf people deploy the same cognitive and learning
      processes in reading as their hearing peers. For this purpose, we analyzed the
      relation between phonological processing, speechreading, vocabulary, reading
      speed, and accuracy with reading efficiency in a sample of deaf people and two
      control groups respectively matched on chronological age and reading level. The
      results indicate that deaf people's level of reading efficiency is lower than
      hearing people's of the same age, but that deafness status in itself is not a
      good predictor of reading level. The results do not support the idea that deaf
      people's reading is the result of different processes from the hearing
      population. 

PMID- 26209447
TI  - Factors Affecting Psychosocial and Motor Development in 3-Year-Old Children Who
      Are Deaf or Hard of Hearing.
AB  - Previous research has shown an association between children's development of
      psychosocial and motor skills. This study evaluated the development of these
      skills in 301 three-year-old deaf and hard of hearing children (M: 37.8 months)
      and considered a range of possible predictors including gender, birth weight, age
      at first fitting with hearing devices, hearing device used, presence of
      additional disabilities, severity of hearing loss, maternal education, socio
      economic status (SES), language ability, and communication mode. Caregivers
      reported on children's development using the Child Development Inventory (CDI).
      On average, both psychosocial and motor development quotients were within the
      typical range for hearing children, with large individual differences. There was
      a positive correlation between language ability and both social and motor
      development, and also between social and motor development. Age at first fitting
      of hearing aids (as an indicator of age at identification of hearing loss), SES,
      degree of hearing loss, and maternal education were not significant predictors of
      social skill or motor development, whereas presence of additional disabilities
      and birth weight were. Girls performed better than boys on all but the Gross
      Motor subscale of the CDI. Children with hearing aids tended to perform better
      than those with cochlear implants on the Gross Motor subscale. 

PMID- 26209449
TI  - Luteal phase ovarian stimulation following oocyte retrieval: is it helpful for
      poor responders?
AB  - BACKGROUND: Poor ovarian response and retrieval of no oocytes following ovarian
      stimulation for in vitro fertilization (IVF) is a challenging problem for both
      the patient and the clinician. FINDINGS: Recent evidence indicates that
      folliculogenesis occurs in a wave-like fashion indicating that there are multiple
      follicular recruitment waves in the same menstrual cycle. This relatively new
      scientific concept provides new opportunities for the utilization of ovarian
      stimulation in women with poor ovarian response. This communication reports on
      the social and scientific rationale for the use of luteal phase ovarian
      stimulation following oocyte retrieval in the same cycle (also called double
      stimulation). CONCLUSIONS: Data to date showed that double ovarian stimulation in
      poor responders provides shorter time for retrieving mature oocytes with the
      potential formation of good quality embryos, and thus healthy pregnancies.

PMID- 26209450
TI  - Cognition and Health Literacy in Older Adults' Recall of Self-Care Information.
AB  - Purpose of the Study: Health literacy is associated with health outcomes
      presumably because it influences the understanding of information needed for self
      care. However, little is known about the language comprehension mechanisms that
      underpin health literacy. Design and Methods: We explored the relationship
      between a commonly used measure of health literacy (Short Test of Functional
      Health Literacy in Adults [STOFHLA]) and comprehension of health information
      among 145 older adults. Results: Results showed that performance on the STOFHLA
      was associated with recall of health information. Consistent with the Process
      Knowledge Model of Health Literacy, mediation analysis showed that both
      processing capacity and knowledge mediated the association between health
      literacy and recall of health information. In addition, knowledge moderated the
      effects of processing capacity limits, such that processing capacity was less
      likely to be associated with recall for older adults with higher levels of
      knowledge. Implications: These findings suggest that knowledge contributes to
      health literacy and can compensate for deficits in processing capacity to support
      comprehension of health information among older adults. The implications of these
      findings for improving patient education materials for older adults with
      inadequate health literacy are discussed.

PMID- 26209451
TI  - Reply: To PMID 26209452.

PMID- 26209452
TI  - Editorial Comment.

PMID- 26209453
TI  - The Difference a Year Can Make: Academic Productivity of Residents in 5 vs 6-Year
      Urology Programs.
AB  - OBJECTIVE: To evaluate the effect of a dedicated research year on academic
      productivity in a heterogeneous group of urology programs. METHODS: We obtained
      information on publication output for the past 5 years, from 2009 to 2013, of
      urology graduates from all 15 New York Section residency programs (n = 148). We
      recorded resident sex; whether the program has a dedicated year of research;
      number of residents per year; total number of publications per resident noting
      first, second, and third or greater authorship; and whether residents pursued
      fellowship training. RESULTS: Overall, the median number of total publications
      was 3 for residents in 5-year programs compared with 7 in 6-year programs (P =
      .0007). This difference remained significant when evaluating the number of
      publications per year as well as the number of first and third or greater
      authorship. Programs with 3 residents per year had significantly more
      publications than those with 1 or 2, regardless of research time. Graduates of 5
      year programs were less likely than their 6-year counterparts to pursue
      fellowship training. There was a significantly higher publication output for
      those residents who went on to fellowship training. On multivariate analysis, 5-
      or 6-year program, the number of residents per year and pursuit of fellowship
      training remained statistically significant predictors of total publication
      number. CONCLUSION: Urology residents with a dedicated year of research produce
      more than 2 times the number of publications than their counterparts in 5-year
      programs. This dedicated research time and greater publication output were both
      indicative of the pursuit of fellowship training.

PMID- 26209454
TI  - Regional mechanical properties of the long head of the biceps tendon.
AB  - BACKGROUND: Long head of the biceps tenodesis reliably relieves pain, and
      restores strength, stability, and normal appearance of the upper extremity in the
      event of biceps tendinopathies. Regional differences in tendon mechanics may
      provide surgeons with valuable guidance in the placement of the tenodesis repair
      construct. The purpose of this study was to compare the mechanical properties of
      the long head of the biceps tendon in three functional regions of the tendon:
      intra-articular (proximal), suprapectoral (middle), and subpectoral (distal).
      METHODS: Uniaxial tensile tests were performed on the long head of the biceps
      tendon segments to quantify the material and structural properties of the tendon.
      Material properties were obtained using dogbone-shaped specimens while structural
      properties were obtained using intact specimens where the clamp boundary
      conditions simulated the common "gold standard" tenodesis, the interference
      screw. FINDINGS: Elastic modulus for the supra- and subpectoral regions were
      significantly greater than the intra-articular region (P<=0.048). The tensile
      strength of the subpectoral region tended to be lower compared to all other
      functional regions (P=0.051). The failure mechanism for intact specimens was
      similar to that seen for interference screw fixation where tissue failure occurs
      due to tearing at the bone/tendon/screw interface. INTERPRETATION: The higher
      tensile strength of the suprapectoral region compared to the subpectoral region
      may make this a more desirable location for tenodesis placement based on tissue
      strength. Similar elastic moduli and structural stiffness between the supra- and
      subpectoral regions indicate that the construct type may play a bigger role in
      functional outcomes in relation to construct deformation.

PMID- 26209455
TI  - Effect of pond water depth on snail populations and fish-borne zoonotic trematode
      transmission in juvenile giant gourami (Osphronemus goramy) aquaculture
      nurseries.
AB  - Infection with fish-borne zoonotic trematodes (FZT) is an important public health
      problem in many parts of Southeast Asia. People become infected with FZT when
      eating raw or undercooked fish that contain the infective stage (metacercariae)
      of FZT. The parasites require specific freshwater snails as first intermediate
      host and a variety of fish species, both wild caught and cultured, as second
      intermediate host. Aquaculture production has grown almost exponentially in SE
      Asia and in order to produce fish free from FZT metacercariae, it is important to
      mitigate factors promoting transmission to fish. Here we report results from a
      cross-sectional study to look at the association between pond depth and infection
      with FZT in giant gourami nursery ponds. Density of intermediate host snails was
      positively associated with pond depth (count ratio associated with a 1m increase
      in pond depth was 10.4 (95% C.L.: 1.61-67.1, p<0.5)) and this may partly explain
      the higher prevalence and intensity of FZT infection in juvenile fish. High fry
      stocking density (>200 fry m(-3)) was associated with lower host snail density
      (count ratio=0.15) than low stocking density (<100 fry m(3)). Ponds stocked with
      100-200 fry m(-3) had snail counts 0.76 (95% C.L.: 0.33-1.75, p n.s.) of those in
      ponds stocked with fry density of <100 fry m(-3). Since density of intermediate
      snail hosts was associated with FZT transmission to fish, effort should be taken
      to reduce snail density prior to stocking the fry, but focus should also be on
      habitats surrounding ponds as transmission may occur through cercariae produced
      outside ponds and carried into ponds with water pumped into ponds.

PMID- 26209456
TI  - A new case of zoonotic onchocercosis in northern Kyushu, Japan.
AB  - A case of zoonotic onchocercosis has been found in a resident who lived in Iizuka
      City, Fukuoka Prefecture, Japan for some time. A 24-year-old male developed a
      painful nodule on the middle finger of his right hand. The nodule was surgically
      removed from the vagina fibrosa tendinis of the finger at Beppu Medical Center,
      Beppu City, Oita Prefecture in 2012. The causative agent was identified as a
      female Onchocerca dewittei japonica based on its histopathological
      characteristics. The identity of the filarioid has been confirmed by sequencing
      the cox1 gene. The present study indicates that the zoonotic onchocercosis caused
      by O. dewittei japonica has been concentrated in northeast Kyushu. 

PMID- 26209457
TI  - Vagus Nerve Mediates the Neural Stem Cell Response to Intestinal Injury.
AB  - BACKGROUND: Intestinal ischemia and reperfusion injury results in damage to
      elements critical to maintaining intestinal barrier function, including neurons
      and glia cells, which are part of the enteric nervous system (ENS). To limit
      inflammation, the ENS must be restored or replaced, yet the process by which this
      occurs is poorly understood. Multipotent progenitor cells called enteric nervous
      stem cells (ENSC) can differentiate into neurons or glia when stimulated. The
      ability of this cell population to respond to intestinal injury is unknown. In
      this study, we hypothesized that resolution of intestinal barrier injury would be
      associated with vagus nerve-mediated expansion of ENSCs. STUDY DESIGN: Ischemia
      and reperfusion injury was reproduced in male mice by occluding the superior
      mesenteric artery for 30 minutes. Abdominal vagotomy was performed in a separate
      cohort to study the effects of the vagus nerve. Terminal ileum was harvested at
      various time points after reperfusion and analyzed with histology, flow
      cytometry, and immunohistochemistry. RESULTS: Enteric nervous stem cell expansion
      occurs at 2, 4, and 8 hours after injury compared with sham (4.6% vs 2.1%; p <
      0.001) and correlated with increased glial fibrillary acidic protein on
      immunohistochemistry. Vagotomy prevented both ENSC expansion and increased glial
      fibrillary acidic protein staining after injury. Intestinal permeability was
      restored to baseline by 48 hours after injury, but remained elevated in the
      vagotomy group compared with sham and injury alone at 48 hours (3.25 mg/mL vs
      0.57 mg/mL and 0.26 mg/mL, respectively; p < 0.05). CONCLUSIONS: Vagal-mediated
      expansion of ENSCs occurs after ischemia and reperfusion injury and results in
      improved kinetics of injury resolution.

PMID- 26209458
TI  - Circulating Epithelial Cells in Patients with Pancreatic Lesions: Clinical and
      Pathologic Findings.
AB  - BACKGROUND: Circulating epithelial cell (CEC) isolation has provided diagnostic
      and prognostic information for a variety of cancers, previously supporting their
      identity as circulating tumor cells in the literature. However, we report CEC
      findings in patients with benign, premalignant, and malignant pancreatic lesions
      using a size-selective filtration device. STUDY DESIGN: Peripheral blood samples
      were drawn from patients found to have pancreatic lesions on preoperative imaging
      at a surgical clinic. Blood was filtered using ScreenCell devices, which were
      evaluated microscopically by a pancreatic cytopathologist. Pathologic data and
      clinical outcomes of these patients were obtained from medical records during a 1
      year follow-up period. RESULTS: Nine healthy volunteers formed the control group
      and were found to be negative for CECs. There were 179 patients with pancreatic
      lesions that formed the study cohort. Circulating epithelial cells were
      morphologically similar in patients with a variety of pancreatic lesions.
      Specifically, CECs were identified in 51 of 105 pancreatic ductal adenocarcinomas
      (49%), 7 of 11 neuroendocrine tumors (64%), 13 of 21 intraductal papillary
      mucinous neoplasms (62%), and 6 of 13 patients with chronic pancreatitis. Rates
      of CEC identification were similar in patients with benign, premalignant, and
      malignant lesions (p = 0.41). In addition, CEC findings in pancreatic ductal
      adenocarcinoma patients were not associated with poor prognosis. CONCLUSIONS:
      Although CECs were not identified in healthy volunteers, they were identified in
      patients with benign, premalignant, and malignant pancreatic lesions. The
      presence of CECs in patients presenting with pancreatic lesions is neither
      diagnostic of malignancy nor prognostic for patients with pancreatic ductal
      adenocarcinoma.

PMID- 26209459
TI  - Extracellular volume quantification by dynamic equilibrium cardiac computed
      tomography in cardiac amyloidosis.
AB  - BACKGROUND: Cardiac involvement determines outcome in patients with systemic
      amyloidosis. There is major unmet need for quantification of cardiac amyloid
      burden, which is currently only met in part through semi-quantitative bone
      scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR.
      Other accessible tests are needed. OBJECTIVES: To develop cardiac computed
      tomography to diagnose and quantify cardiac amyloidosis by measuring the
      myocardial Extracellular Volume, ECVCT. METHODS: Twenty-six patients (21 male, 64
      +/- 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8)
      were compared with twenty-seven patients (19 male, 68 +/- 8 years) with severe
      aortic stenosis (AS). All patients had undergone echocardiography, bone
      scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ
      CT) was performed using a prospectively gated cardiac scan prior to and after (5
      and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was
      compared to the reference ECVCMR and conventional amyloid measures: bone
      scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP,
      Troponin, LVEF, LV mass, LA and RA area). RESULTS: ECVCT and ECVCMR results were
      well correlated (r(2) = 0.85 vs r(2) = 0.74 for 5 and 15 minutes post bolus
      respectively). ECVCT was higher in amyloidosis than AS (0.54 +/- 0.11 vs 0.28 +/-
      0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid
      severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone
      scintigraphy amyloid burden (p<0.001). CONCLUSION: Dynamic Equilibrium CT, a 5
      minute contrast-enhanced gated cardiac CT, has potential for non-invasive
      diagnosis and quantification of cardiac amyloidosis.

PMID- 26209460
TI  - Structural and biochemical properties of LuxF from Photobacterium leiognathi.
AB  - The lux-operon of bioluminescent bacteria contains the genes coding for the
      enzymes required for light emission. Some species of Photobacteria feature an
      additional gene, luxF, which shows similarity to luxA and luxB, the genes
      encoding the heterodimeric luciferase. Isolated dimeric LuxF binds four molecules
      of an unusually derivatized flavin, i.e., 6-(3'-(R)-myristyl)-FMN (myrFMN). In
      the present study we have heterologously expressed LuxF in Escherichia coli BL21
      in order to advance our understanding of the protein's binding properties and its
      role in photobacterial bioluminescence. Structure determination by X-ray
      crystallography confirmed that apo-LuxF possesses four preorganized binding
      sites, which are further optimized by adjusting the orientation of amino acid
      side chains. To investigate the binding properties of recombinant LuxF we have
      isolated myrFMN from Photobacterium leiognathi S1. We found that LuxF binds
      myrFMN tightly with a dissociation constant of 80+/-20 nM demonstrating that the
      purified apo-form of LuxF is fully competent in myrFMN binding. In contrast to
      LuxF, binding of myrFMN to luciferase is much weaker (Kd=4.0+/-0.4 MUM) enabling
      LuxF to prevent inhibition of the enzyme by scavenging myrFMN. Moreover, we have
      used apo-LuxF to demonstrate that myrFMN occurs in all Photobacteria tested,
      irrespective of the presence of luxF indicating that LuxF is not required for
      myrFMN biosynthesis.

PMID- 26209461
TI  - The multi-faceted aspects of the complex cardiac Nav1.5 protein in membrane
      function and pathophysiology.
AB  - The aim of this mini-review is to draw together the main concepts and findings
      that have emerged from recent studies of the cardiac channel protein Nav1.5. This
      complex protein is encoded by the SCN5A gene that, in its mutated form, is
      implicated in various diseases, particularly channelopathies, specifically at
      cardiac tissue level. Here we describe the structural, and functional aspects of
      Nav1.5 including post-translational modifications in normal conditions, and the
      main human channelopathies in which this protein may be the cause or trigger.
      Lastly, we also briefly discuss interacting proteins that are relevant for these
      channel functions in normal and disease conditions. 

PMID- 26209462
TI  - Heat stress, dehydration, and kidney function in sugarcane cutters in El Salvador
      -A cross-shift study of workers at risk of Mesoamerican nephropathy.
AB  - BACKGROUND: An epidemic of progressive kidney failure afflicts sugarcane workers
      in Central America. Repeated high-intensity work in hot environments is a
      possible cause. OBJECTIVES: To assess heat stress, dehydration, biomarkers of
      renal function and their possible associations. A secondary aim was to evaluate
      the prevalence of pre-shift renal damage and possible causal factors. METHODS:
      Sugarcane cutters (N=189, aged 18-49 years, 168 of them male) from three regions
      in El Salvador were examined before and after shift. Cross-shift changes in
      markers of dehydration and renal function were examined and associations with
      temperature, work time, region, and fluid intake were assessed. Pre-shift
      glomerular filtration rate was estimated (eGFR) from serum creatinine. RESULTS:
      The mean work-time was 4 (1.4-11) hours. Mean workday temperature was 34-36 
      degrees C before noon, and 39-42  degrees C at noon. The mean liquid intake
      during work was 0.8L per hour. There were statistically significant changes
      across shift. The mean urine specific gravity, urine osmolality and creatinine
      increased, and urinary pH decreased. Serum creatinine, uric acid and urea
      nitrogen increased, while chloride and potassium decreased. Pre-shift serum uric
      acid levels were remarkably high and pre-shift eGFR was reduced (<60 mL/min) in
      23 male workers (14%). CONCLUSIONS: The high prevalence of reduced eGFR, and the
      cross-shift changes are consistent with recurrent dehydration from strenuous work
      in a hot and humid environment as an important causal factor. The pathophysiology
      may include decreased renal blood flow, high demands on tubular reabsorption, and
      increased levels of uric acid.

PMID- 26209463
TI  - Origins of feature selectivities and maps in the mammalian primary visual cortex.
AB  - A common feature of the mammalian striate cortex is the arrangement of
      'orientation domains' containing neurons preferring similar stimulus
      orientations. They are arranged as spokes of a pinwheel that converge at
      singularities known as 'pinwheel centers'. We propose that a cortical network of
      feedforward and intracortical lateral connections elaborates a full set of
      optimum orientations from geniculate inputs that show a bias to stimulus
      orientation and form a set of two or a small number of 'Cartesian' coordinates.
      Because each geniculate afferent carries signals only from one eye and its
      receptive field (RF) is either ON or OFF center, the network constructs also
      ocular dominance columns and a quasi-segregation of ON and OFF responses across
      the horizontal extent of the striate cortex. 

PMID- 26209464
TI  - The cellular and molecular landscape of neuroligins.
AB  - A fundamental physical interaction exists across the synapse. It is mediated by
      synaptic adhesion molecules, and is among the earliest and most indispensable of
      molecular events occurring during synaptogenesis. The regulation of adhesion
      molecules and their interactions with other synaptic proteins likely affect not
      only on synapse formation but also on ongoing synaptic function. We review
      research on one major family of postsynaptic adhesion molecules, neuroligins,
      which bind to their presynaptic partner neurexin across the synaptic cleft. We
      move from a structural overview to the broad cellular and synaptic context of
      neuroligins, intermolecular interactions, and molecular modifications that occur
      within a synapse. Finally, we examine evidence concerning the physiological
      functions of neuroligin in a cell and highlight areas requiring further
      investigation. 

PMID- 26209465
TI  - Aortic graft in hollow viscus.
AB  - Secondary aortoenteric fistulas (AEFs) and aortic graft infection are relatively
      rare but fatal complications of aortic surgery. A 77-year-old man had a 1-week
      history of fever and abdominal pain with right inguinal area swelling. The
      patient's medical history included hypertension, aortobifemoral bypass grafting
      due to right iliac artery, and superficial femoral artery occlusion.
      Abdominopelvic computed tomography revealed the presence of an aortic graft in
      the hollow viscus. Although there have been several reports of secondary AEF,
      there have been few reports of an aortic graft in a hollow viscus. Diagnosis of
      AEF can be delayed in patients with atypical symptoms. Without a high index of
      suspicion, this condition has fatal consequences.

PMID- 26209466
TI  - Novel vagal maneuver technique for termination of supraventricular tachycardias.
AB  - Hemodynamically unstable patients with supraventricular tachycardias (SVTs)
      should be treated with electrical cardioversion. If the patient is stable, acute
      termination of tachycardia can be achieved by vagal maneuvers or medical therapy.
      The Valsalva maneuver, carotid massage, and ice to the face are the most common
      vagal maneuvers. In our experience with patients, we observed that vagal
      stimulation increases with lying backward. Our suggested maneuver is based on
      quickly lying backward, from a seated position. Then, a short and powerful vagal
      stimulation occurs. Thus, SVT episodes can be terminated. Here we present our
      experience of a new maneuver for terminating SVT, with cases.

PMID- 26209467
TI  - The still lung point: new sonographic evidence for pneumomediastinum.

PMID- 26209468
TI  - Naturopathic Oncology Modified Delphi Panel.
AB  - Naturopathic oncology is a relatively new and emerging field capable of providing
      professional integrative or alternative services to cancer patients. Foundational
      research is critical to identify topics in the clinical and research development
      of naturopathic oncology for future growth of the field. STUDY DESIGN: This study
      implements a modified Delphi protocol to develop expert consensus regarding
      ethics, philosophy, and research development in naturopathic oncology. METHODS:
      The modified protocol implements a nomination process to select a panel of 8
      physicians and to assist in question formulation. The protocol includes an in
      person discussion of 6 questions with multiple iterations to maintain the concept
      of the Delphi methodology as well as a postdiscussion consensus survey. RESULTS:
      The protocol identified, ranked, and established consensus for numerous themes
      per question. Underlying key topics include integration with conventional
      medicine, evidence-based medicine, patient education, patient safety, and
      additional training requirements for naturopathic oncologists. CONCLUSIONS: The
      systematic nomination and questioning of a panel of experts provides a
      foundational and educational resource to assist in clarification of clinical
      ethics, philosophy, and research development in the emerging field of
      naturopathic oncology.

PMID- 26209469
TI  - Effectiveness of MIS technique as a treatment modality for open intra-articular
      calcaneal fractures: A prospective evaluation with matched closed fractures
      treated by conventional technique.
AB  - Twenty-five displaced intra-articular calcaneal fractures in 21 patients, aged 15
      55 years were included in this study. Sanders' type I fractures, severe crushing
      or partial amputation, were excluded from the study. Patients were divided into
      group 1 (open fractures treated by MIS), and group 2 (closed fractures treated by
      ORIF). Group 1 had 16 and group 2 had 9 cases. Seven of 25 fractures (28%)
      developed wound related issues postoperatively. One patient (11.1%) in group 2
      had wound margin necrosis, while 6 patients (37.5%) in group 1 developed pin
      tract and/or wound infection. At 1-year follow-up, the mean MFS for group 1 was
      79 and mean MFS for group 2 was 84.4 (66.67% were good). The AOFAS score for
      group 1 was 77.37 and for group 2 was 86.1. The Bohlers' angle was restored in
      81.16% cases in group 1 and 88.8% in group 2, while Gissane angle was restored in
      68.75% of group 1 cases and 77.79% of group 2 cases. This study shows that
      acceptable fracture reduction can be obtained and maintained by MIS technique and
      it can be used as the primary definitive treatment option in open calcaneal
      fractures. 

PMID- 26209470
TI  - Treatment of anterior tarsal tunnel syndrome through an endoscopic or open
      technique.
AB  - Anterior tarsal tunnel syndrome is often underdiagnosed, due to lack of clinical
      awareness and vague clinical presentation. Most often patients complain of pain
      located to the dorsum of the foot. The present study is a consecutive series of
      13 patients treated according to a fixed protocol followed for a minimum of 24
      months. A total of 12/13 cases presented with a bulge in the anterior part of the
      ankle or the dorsal foot and Tinel's sign was positive over it. Only half had
      decreased sensation. Surgical technique was either endoscopic or open. Endoscopy
      is preferable when compression is due to an osteophyte (4/13) or an isolated
      ganglion 2/13). In other cases presenting with synovitis (5/13) or unknown
      etiology (2/13) performing open surgery was deemed as safer. The American
      Orthopedic Foot and Ankle Society (AOFAS) hindfoot scores improved from an
      average of 55 +/- 8 to 83 +/- 11 at 12 months after surgery and 88 +/- 10 at 24
      months after surgery. The anterior tarsal tunnel syndrome accounts for
      approximately 5% of cases complaining of feet numbness, which undergo
      electromyographic and nerve conduction testing. Reports in the scientific
      literature are scarce, perhaps due to underdiagnosis, while it is amenable to
      surgical management. Clinical diagnosis supported by imaging studies demonstrated
      osteophytes, ganglions or localized synovitis. Endoscopic treatment can be
      performed safely provided a clear-cut single compressing element is identified.

PMID- 26209471
TI  - Agreement Between Responses From Community-Dwelling Persons With Stroke and Their
      Proxies on the NIH Neurological Quality of Life (Neuro-QoL) Short Forms.
AB  - OBJECTIVE: To examine agreement between patient and proxy responses on the
      Quality of Life in Neurological Disorders (Neuro-QoL) instruments after stroke.
      DESIGN: Cross-sectional observational substudy of the longitudinal, multisite,
      multicondition Neuro-QoL validation study. SETTING: In-person, interview-guided,
      patient-reported outcomes. PARTICIPANTS: Convenience sample of dyads (N=86) of
      community-dwelling persons with stroke and their proxy respondents.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Dyads concurrently
      completed short forms of 8 or 9 items for the 13 Neuro-QoL adult domains using
      the patient-proxy perspective. Agreement was examined at the scale-level with
      difference scores, intraclass correlation coefficients (ICCs), effect size
      statistics, and Bland-Altman plots, and at the item-level with kappa
      coefficients. RESULTS: We found no mean differences between patients and proxies
      on the Applied Cognition-General Concerns, Depression, Satisfaction With Social
      Roles and Activities, Stigma, and Upper Extremity Function (Fine Motor,
      activities of daily living) short forms. Patients rated themselves more favorably
      on the Applied Cognition-Executive Function, Ability to Participate in Social
      Roles and Activities, Lower Extremity Function (Mobility), Positive Affect and
      Well-Being, Anxiety, Emotional and Behavioral Dyscontrol, and Fatigue short
      forms. The largest mean patient-proxy difference observed was 3 T-score points on
      the Lower Extremity Function (Mobility). ICCs ranged from .34 to .59. However,
      limits of agreement showed dyad differences exceeding +/-20 T-score points, and
      item-level agreement ranged from not significant to weighted kappa=.34.
      CONCLUSIONS: Proxy responses on Neuro-QoL short forms can complement responses of
      moderate- to high-functioning community-dwelling persons with stroke and augment
      group-level analyses, but do not substitute for individual patient ratings.
      Validation is needed for other stroke populations.

PMID- 26209472
TI  - Protein aggregation and neurodegeneration in prototypical neurodegenerative
      diseases: Examples of amyloidopathies, tauopathies and synucleinopathies.
AB  - Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative
      diseases that generate important health-related direct and indirect socio
      economic costs. They are characterized by severe neuronal losses in several
      disease-specific brain regions associated with deposits of aggregated proteins.
      In Alzheimer's disease, beta-amyloid peptide-containing plaques and intraneuronal
      neurofibrillary tangles composed of hyperphosphorylated microtubule-associated
      protein tau are the two main neuropathological lesions, while Parkinson's disease
      is defined by the presence of Lewy Bodies that are intraneuronal proteinaceous
      cytoplasmic inclusions. alpha-Synuclein has been identified as a major protein
      component of Lewy Bodies and heavily implicated in the pathogenesis of
      Parkinson's disease. In the past few years, evidence has emerged to explain how
      these aggregate-prone proteins can undergo spontaneous self-aggregation,
      propagate from cell to cell, and mediate neurotoxicity. Current research now
      indicates that oligomeric forms are probably the toxic species. This article
      discusses recent progress in the understanding of the pathogenesis of these
      diseases, with a focus on the underlying mechanisms of protein aggregation, and
      emphasizes the pathophysiological molecular mechanisms leading to cellular
      toxicity. Finally, we present the putative direct link between beta-amyloid
      peptide and tau in causing toxicity in Alzheimer's disease as well as alpha
      synuclein in Parkinson's disease, along with some of the most promising
      therapeutic strategies currently in development for those incurable
      neurodegenerative disorders.

PMID- 26209474
TI  - A Practical Application of Value of Information and Prospective Payback of
      Research to Prioritize Evaluative Research.
AB  - BACKGROUND AND OBJECTIVES: Efforts to ensure that funded research represents
      "value for money" have led to increasing calls for the use of analytic methods in
      research prioritization. A number of analytic approaches have been proposed to
      assist research funding decisions, the most prominent of which are value of
      information (VOI) and prospective payback of research (PPoR). Despite the
      increasing interest in the topic, there are insufficient VOI and PPoR
      applications on the same case study to contrast their methods and compare their
      outcomes. We undertook VOI and PPoR analyses to determine the value of conducting
      2 proposed research programs. The application served as a vehicle for identifying
      differences and similarities between the methods, provided insight into the
      assumptions and practical requirements of undertaking prospective analyses for
      research prioritization, and highlighted areas for future research. METHODS: VOI
      and PPoR were applied to case studies representing proposals for clinical trials
      in advanced non-small-cell lung cancer and prostate cancer. Decision models were
      built to synthesize the evidence available prior to the funding decision. VOI
      (expected value of perfect and sample information) and PPoR (PATHS model)
      analyses were undertaken using the developed models. RESULTS AND CONCLUSIONS: VOI
      and PPoR results agreed in direction, suggesting that the proposed trials would
      be cost-effective investments. However, results differed in magnitude, largely
      due to the way each method conceptualizes the possible outcomes of further
      research and the implementation of research results in practice. Compared with
      VOI, PPoR is less complex but requires more assumptions. Although the approaches
      are not free from limitations, they can provide useful input for research funding
      decisions.

PMID- 26209473
TI  - Pathophysiology of L-dopa-induced motor and non-motor complications in
      Parkinson's disease.
AB  - Involuntary movements, or dyskinesia, represent a debilitating complication of
      levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia
      (LID) are ultimately experienced by the vast majority of patients. In addition,
      psychiatric conditions often manifested as compulsive behaviours, are emerging as
      a serious problem in the management of L-dopa therapy. The present review
      attempts to provide an overview of our current understanding of dyskinesia and
      other L-dopa-induced dysfunctions, a field that dramatically evolved in the past
      twenty years. In view of the extensive literature on LID, there appeared a
      critical need to re-frame the concepts, to highlight the most suitable models, to
      review the central nervous system (CNS) circuitry that may be involved, and to
      propose a pathophysiological framework was timely and necessary. An updated
      review to clarify our understanding of LID and other L-dopa-related side effects
      was therefore timely and necessary. This review should help in the development of
      novel therapeutic strategies aimed at preventing the generation of dyskinetic
      symptoms. 

PMID- 26209475
TI  - Exclusion Criteria in National Health State Valuation Studies: A Systematic
      Review.
AB  - BACKGROUND: Health state valuation data are often excluded from studies that aim
      to provide a nationally representative set of values for preference-based health
      related quality of life (HRQoL) instruments. The purpose was to provide a
      systematic examination of exclusion criteria used in the derivation of societal
      scoring algorithms for preference-based HRQoL instruments. METHODS: Data sources
      included MEDLINE, official instrument websites, and publication reference lists.
      Analyses that used data from national valuation studies and reported a scoring
      algorithm for a generic preference-based HRQoL instrument were included. Data
      extraction included exclusion criteria and associated justifications, exclusion
      rates, the characteristics of excluded respondents, and analyses that explored
      consequential implications of exclusion criteria on the respective national
      tariff. RESULTS: Seventy-six analyses (from 70 papers) met the inclusion
      criteria. In addition to being excluded for logical inconsistencies, respondents
      were often excluded if they valued fewer than 3 health states or if they gave the
      same value to all health states. Numerous other exclusion criteria were
      identified, with varying degrees of justification, often based on an assumption
      that respondents did not understand the task or as a consequence of the chosen
      statistical modeling techniques. Rates of exclusion ranged from 0% to 65%, with
      excluded respondents more likely to be older, less educated, and less healthy.
      Limitations included that the database search was confined to MEDLINE; study
      selection focused on national valuation studies that used standard gamble, time
      tradeoff, and/or visual analog scale techniques; and only English-language
      studies were included. CONCLUSION: Exclusion criteria used in national valuation
      studies vary considerably. Further consideration is necessary in this important
      and influential area of research, from the design stage to the reporting of
      results.

PMID- 26209476
TI  - Valuation of Child Behavioral Problems from the Perspective of US Adults.
AB  - OBJECTIVE: To assess preferences between child behavioral problems and estimate
      their value on a quality-adjusted life year (QALY) scale. METHODS: Respondents,
      age 18 or older, drawn from a nationally representative panel between August 2012
      and February 2013 completed a series of paired comparisons, each involving a
      choice between 2 different behavioral problems described using the Behavioral
      Problems Index (BPI), a 28-item instrument with 6 domains (Anxious/Depressed,
      Headstrong, Hyperactive, Immature Dependency, Anti-social, and Peer
      Conflict/Social Withdrawal). Each behavioral problem lasted 1 or 2 years for an
      unnamed child, age 7 or 10 years, with no suggested relationship to the
      respondent. Generalized linear model analyses estimated the value of each problem
      on a QALY scale, considering its duration and the child's age. RESULTS: Among
      5207 eligible respondents, 4155 (80%) completed all questions. Across the 6
      domains, problems relating to antisocial behavior were the least preferred,
      particularly the items related to cheating, lying, bullying, and cruelty to
      others. CONCLUSIONS: The findings are the first to produce a preference-based
      summary measure of child behavioral problems on a QALY scale. The results may
      inform both clinical practice and resource allocation decisions by enhancing our
      understanding of difficult tradeoffs in how adults view child behavioral
      problems. Understanding US values also promotes national health surveillance by
      complementing conventional measures of surveillance, survival, and diagnoses.

PMID- 26209477
TI  - Interobserver variations of target volume delineation in multicatheter partial
      breast brachytherapy after open cavity surgery.
AB  - PURPOSE: To investigate interobserver variations of target volume delineations in
      accelerated partial breast irradiation with multicatheter brachytherapy (BT) and
      to assess the impact of guidelines on consistency of contouring. METHODS AND
      MATERIALS: A contouring study with two phases in interstitial accelerated partial
      breast irradiation after open cavity surgery was conducted by the Groupe Europeen
      de Curietherapie-European Society for Radiotherapy and Oncology Breast Cancer
      Working Group. Contours of cavity and planning target volume (PTV) on preimplant
      and postimplant CT images were delineated. In Phase 1, nine radiation oncologists
      defined the target volumes of 5 patients, whereas in Phase 2, four observers draw
      the contours of 4 patients applying guidelines. In Phase 1, experience in breast
      BT after open cavity surgery was assessed. The delineations were compared between
      Phase 1 and Phase 2, the impact of guidelines was assessed, and cavity
      visualization score was related to consistency of delineations. RESULTS:
      Significant interobserver variability in delineations of lumpectomy cavity and
      PTV was observed among the participants. Observers with BT experience after open
      cavity surgery outlined the cavity and PTV more consistently (conformity
      indexgen: 0.52 vs. 0.48 and 0.59 vs. 0.55 for preimplant and postimplant
      cavities). For all volumes, the mean Vmax/Vmin was 2.2 vs. 2.8. Having used
      guidelines all conformity indices increased significantly. For cavity, the
      increase was 14% and 11%, whereas for the PTV, 28% and 17% on the preimplant and
      postimplant CT images, respectively. A strong correlation was found between
      consistency of contours and cavity visualization score. CONCLUSIONS: Simple
      guidelines on defining the lumpectomy cavity significantly increased the
      consistency of contouring. Reliable consistency of target volume definition can
      be expected only for good cavity visibility.

PMID- 26209478
TI  - Personality domains, duration of untreated psychosis, functioning, and symptom
      severity in first-episode psychosis.
AB  - OBJECTIVES: Early-course psychotic disorders have been extensively studied in
      terms of phenomenology, but little is known about the influence of personality
      traits on clinical features of first-episode psychosis. The aim of this study was
      to explore how the "big five" personality domains (neuroticism, extraversion,
      openness, agreeableness, and conscientiousness) are associated with treatment
      delay (duration of untreated psychosis, DUP), functioning, and positive and
      negative symptom severity. METHODS: Data for these analyses were obtained from
      104 participants enrolled from psychiatric inpatient units in Atlanta, Georgia,
      between August 2008 and March 2011. The NEO Five-Factor Inventory (NEO-FFI) was
      used to assess personality domains, and all other variables were measured in a
      standardized and rigorous manner using psychometrically sound instruments.
      Correlational analyses and multiple linear regressions were carried out to
      examine the strength of associations between variables of interest. RESULTS:
      Findings indicated that except for openness, all of the other personality
      variables contributed to some extent to the variance in DUP. Conscientiousness
      was positively correlated with functioning. Agreeableness was independently
      negatively associated with positive symptom severity and extraversion was
      independently negatively correlated with negative symptom severity. CONCLUSIONS:
      We report the first evidence suggesting that DUP is in part driven by personality
      domains. Functioning and symptom severity are also associated with those domains.
      Personality should be taken into account in order to better understand the
      phenomenology of early-course psychotic disorders as well as treatment-seeking
      behaviors.

PMID- 26209479
TI  - Pulmonary-Valve Replacement in Adults: Results With the Medtronic Freestyle
      Valve.
AB  - BACKGROUND: We used the Medtronic Freestyle valve (Medtronic, Minneapolis, MN) as
      an orthotopic conduit in pulmonary valve replacement in repaired tetralogy of
      Fallot and as part of the Ross procedure. Midterm outcomes and hemodynamic status
      of this conduit were analyzed and performances in both subgroups were compared.
      METHODS: From February 2002 to July 2012, 115 Freestyle valves were implanted in
      52 patients with tetralogy of Fallot and 63 patients within the Ross procedure.
      Preoperative and perioperative data were reviewed retrospectively in this
      bicentric study. RESULTS: Mean age at valve surgery was 37 +/- 13 years. Median
      implanted valve size was 27 mm (21 to 29). Early postoperative mortality was
      3.48%. There was 100% follow-up for the survivors at a mean of 4.38 +/- 2.52
      years. There was 1 case of thromboembolism (0.89%), 6 endocarditis (5.4%), and 9
      (7.8%) conduit re-interventions. Echocardiography at discharge and last follow-up
      showed average peak systolic transvalvular gradients of 12.4 +/- 5.1 and 18.7 +/-
      8.8 mm Hg, respectively. Ten patients had significant proximal anastomotic
      gradients of greater than 50 mm Hg and 4 moderate conduit regurgitations.
      Survival was 96.52%. No valve degeneration was seen in 87.82% at 5 years. The
      only risk factor identified for valve re-intervention was conduit implantation
      without infundibular hood (p = 0.01 in multivariate analysis). CONCLUSIONS: Mid
      term data show that Freestyle valves are well suited for pulmonary valve
      replacement in adults in both categories. The surgical technique used in valve
      implantation is important to ensure conduit durability. These results and
      accessibility to the Freestyle valve make this an acceptable alternative to
      homografts.

PMID- 26209480
TI  - Contemporary Outcomes of Repeat Aortic Valve Replacement: A Benchmark for
      Transcatheter Valve-in-Valve Procedures.
AB  - BACKGROUND: Reoperative aortic valve replacement (re-AVR) after previous AVR is a
      complex procedure involving redo sternotomy and removal of a previous prosthesis.
      With increasing use of valve-in-valve transcatheter aortic valve replacement for
      failed aortic bioprostheses, an evaluation of contemporary outcomes of re-AVR in
      patients with bioprostheses is warranted. METHODS: The study included 3,380
      patients from The Society of Thoracic Surgeons Adult Cardiac Surgery Database
      (July 2011 to September 2013) who underwent elective, isolated re-AVR after a
      previous AVR. Outcomes in these patients were compared with those of 54,183
      patients with isolated primary AVR during the same period. A subgroup analysis of
      explanted bioprostheses in re-AVR (previous bioprosthetic valve: n = 2,213) was
      performed. RESULTS: Re-AVR patients were younger (66 vs 70 years, p < 0.001)
      compared with primary AVR patients. Re-AVR was associated with higher operative
      mortality (4.6% vs 2.2%, p < 0.0001), composite operative mortality and major
      morbidity (21.6% vs 11.8%, p < 0.0001), postoperative stroke (1.9% vs 1.4%, p =
      0.02), postoperative aortic insufficiency mild or greater (2.8% vs 1.7%, p <
      0.0001), pacemaker requirement (11.0% vs 4.3%, p < 0.0001), and vascular
      complications (0.06% vs 0.01%, p = 0.04). For the explanted previous
      bioprosthetic valve group, operative mortality was 4.7%, composite outcome was
      21.9%, stroke rate was 1.8%, and pacemaker requirement was 11.5%. CONCLUSIONS: Re
      AVR is now performed with an acceptable operative mortality, which is higher than
      primary AVR. The overall incidence of stroke, vascular complication, and
      postoperative aortic insufficiency was low although higher than primary AVR.
      These results may serve as a benchmark for future analysis of valve-in-valve
      transcatheter aortic valve replacement and may have an effect on future choice of
      transcatheter aortic valve replacement vs re-AVR.

PMID- 26209481
TI  - Radio-Guided Localization and Resection of Small or Ill-Defined Pulmonary
      Lesions.
AB  - BACKGROUND: Screening programs have increased the identification of small or
      indistinct pulmonary lesions that are difficult to localize. We report our
      experience in their preoperative localization by radiotracer and resection.
      METHODS: Patients with pulmonary nodules of subsolid morphology or smaller than 1
      cm, deeper 1 cm below the visceral pleura, or both underwent computed tomography
      (CT)-guided injection of radiotracer technetium 99m macroaggregates in the
      vicinity of the lesion. During the operation, a handheld gamma probe was used to
      detect the hot spot where the radioactive tracer was localized, and this area was
      resected. RESULTS: From November 2007 to May 2013, 112 patients (58 men; median
      age 62 years) underwent preoperative radiotracer injection with a successful
      marking in all patients. Adverse events included 33 (29.4%) pneumothoraces (one
      requiring chest tube placement), 23 (20.5%) parenchymal hemorrhage suffusions,
      and 1 (0.9%) allergic reaction to contrast medium. In all cases except two, the
      gamma probe revealed pulmonary lesions. Overall, 123 pulmonary nodules were
      localized and resected. The mean distance from the pleura was 12 mm (range, 0 to
      39 mm). Pulmonary resection was performed by thoracoscopy in 70 (62.5%) cases,
      thoracotomy in 36 (32.1%), and conversion of thoracoscopy to thoracotomy in 6
      (5.4%). The mean nodule size was 9 mm (range, 3 to 24 mm). Histology showed 14
      (11.4%) benign lesions and 109 (88.6%) malignant lesions (85 primary lung cancers
      and 24 metastases). CONCLUSIONS: Radiotracer localization of pulmonary lesions is
      a simple and feasible procedure with a high rate of success. Optimal candidates
      are patients with suspicious-looking nodules detected by screening or incidental
      CT resulting frm the high rate of nonsolid morphology and small size.

PMID- 26209482
TI  - Surgical Techniques and Long-Term Results of Pulmonary Artery Reconstruction in
      Patients With Lung Cancer.
AB  - BACKGROUND: Pulmonary artery (PA) reconstruction for lung cancer is technically
      feasible with low morbidity and mortality. We assessed our experience with
      partial or circumferential resection of the PA during lung resection. METHODS:
      Between 1998 and 2013, we performed PA angioplasty in 150 patients with lung
      cancer. Partial PA resection was performed in 146 patients. PA reconstruction was
      performed by running suture in 113 patients and by using a pericardial patch in
      33. A circumferential PA resection was performed in 4 patients, and
      reconstruction was made with polytetrafluoroethylene and by a custom-made bovine
      pericardial conduit. Bronchial sleeve resection was associated in 56 patients.
      Stage I disease was present in 32 patients, stage II in 43, stage IIIA in 51, and
      stage IIIB in 17. Seventy-five patients received induction chemotherapy, and 7
      patients had a complete response. RESULTS: Thirty-day mortality was 3.3% (n = 5);
      two of these patients died of a massive hemoptysis. Pulmonary complications
      occurred in 33 patients, cardiac in 28, and air leaks in 17. Overall 5-year and
      10-year survival was 50% and 39%, respectively. Survival at 5 and 10 years for
      stages I and II vs stage III was, respectively, 66% vs 32% and 56% vs 20% (p <
      0.0001). Five-year survival was 61% for N0 and N1 nodal involvement vs 28% for
      N2, and the respective 10-year survival was 45% vs 28% (p = 0.001). Induction
      chemotherapy did not influence survival. Multivariate analysis yielded advanced
      stage, N2 status, and squamous cell carcinoma as negative prognostic factors.
      CONCLUSIONS: PA reconstruction is safe, with excellent long-term survival. Our
      results support this technique as an effective option to pneumonectomy for
      patients with lung cancer.

PMID- 26209483
TI  - Bundled Payments in Cardiac Surgery: Is Risk Adjustment Sufficient to Make It
      Feasible?
AB  - BACKGROUND: Policymakers have proposed risk-adjusted bundled payment as the
      single most promising method of linking reimbursement to value rather than to
      quantity of service. Our objective was to assess the relationship between risk
      and cost to develop a model for forecasting the costs of cardiac operations under
      a bundled payment scheme. METHODS: All patients undergoing adult cardiac
      operations for which there was a Society of Thoracic Surgeons (STS) risk score
      over a 5-year period (2008 to 2013) at a tertiary care, university hospital were
      reviewed. Patients were stratified into five groups based on preoperative risk as
      a basis for negotiating risk-adjusted bundles. A multivariable regression model
      was developed to analyze the relationship between risk and log-transformed costs.
      Monte Carlo simulation was performed to validate the model by comparing predicted
      with actual fiscal year 2013 costs. RESULTS: Among the 2,514 patients analyzed,
      preoperative risk was strongly correlated with costs (p < 0.001) but was able to
      explain only 28% (R(2) = 0.28) of the variation in costs between individual
      patients. The use of bundling to diffuse and adjust for risk improved prediction
      to only 33% (R(2) = 0.33). Actual costs in 2013 were $21.6M compared with
      predicted costs of $19.3M (+/-$350K), which is well outside the forecast's 95%
      confidence interval. CONCLUSIONS: Even among the most routine cardiac operations
      and with use of the most widely validated surgical risk score available, much of
      the variation in costs cannot be explained by preoperative risk or surgeon.
      Consequently, policymakers should reexamine whether individual practices or
      insurers are best suited to manage the residual financial risk.

PMID- 26209484
TI  - Pulmonary Artery Sealing Using the HARMONIC ACE+ Shears for Video-Assisted
      Thoracoscopic Surgery Lobectomy.
AB  - BACKGROUND: The standard technique for pulmonary arterial (PA) branch sealing in
      video-assisted thoracoscopic surgery lobectomy consists of vascular endostaplers.
      We evaluated the immediate efficacy of an ultrasonic energy vessel-sealing device
      for sealing PA branches and compared it with the gold standard (endostapler) in
      an ex vivo model. METHODS: This was a prospective cohort study. Immediately after
      anatomical lung resection, PA vessel sealing was achieved using the HARMONIC ACE+
      Shears (ACE; Ethicon, Cincinnati, OH) sealing device or a vascular endostapler
      (VES) in a 3:1 ratio based on vessel diameter. The vessel was slowly pressurized,
      and the bursting pressure was recorded. RESULTS: A total of 137 PA branches were
      sealed in specimens from 43 patients, of which 90 vessels were sealed with ACE
      and 47 were sealed with VES. The mean PA branch diameter was 6.0 mm (range, 1.7
      mm to 24.0 mm; standard deviation, 3.1 mm Hg). The mean bursting pressure was
      333.0 mm Hg (range, 84.0 mm Hg to 1415.1 mm Hg; standard deviation, 231.4 mm Hg)
      in the ACE group and 114.2 mm Hg (range, 0 mm Hg to 840.0 mm Hg; standard
      deviation, 124.7) in the VES group (p < 0.001). There were no complete sealing
      failures in the ACE group. Electron microscopy of ACE-sealed PA vessels
      demonstrated adventitial sealing with partial preservation of the collagen
      bundles and media with a sealed matrix of melted collagen. CONCLUSIONS: PA
      branches sealed using the HARMONIC ACE+ in a simulated ex vivo model were able to
      sustain high intraluminal pressures. ACE-sealed vessels burst at mean bursting
      pressures equal to or greater than the VES-stapled vessels.

PMID- 26209485
TI  - Safety of Intracoronary Human Cord Blood Stem Cells in a Lamb Model of Infant
      Cardiopulmonary Bypass.
AB  - BACKGROUND: One potential approach for advancing univentricular heart surgical
      palliation outcomes is by stem cell therapy to augment right ventricular function
      and muscle mass. Whether the stem cell-inclusive cord blood mononuclear cells
      (CBMNCs) are safe to perfuse into the coronary vasculature during neonatal
      cardiopulmonary bypass (CPB) is unknown. We evaluated the acute safety,
      functional effects, and fate of human CBMNCs in a novel model of coronary
      vasculature delivery in a lamb model of infant CPB. METHODS: Neonatal lambs were
      randomized in blinded fashion to receive control (n = 5) or human CD45(+) CBMNCs
      (8 * 10(6) cells/kg body weight, n = 7) treatments during CPB. Aortic cross-clamp
      time was 40 minutes, with maintenance blood cardioplegia delivered every 10
      minutes. Pressure-volume indices were used to measure left ventricular function
      before CPB and 60 minutes after CPB. CBMNCs were assessed by flow cytometry and
      immunohistochemistry. RESULTS: CBMNC-treated lambs were hemodynamically stable
      after CPB, with a decline in left ventricular pressure-volume indices similar to
      controls. The coronary vasculature was patent on microscopy, without evidence of
      cell aggregates or clots. Human CD45(+) cells were distributed in high abundance
      within all cardiac regions, predominantly the right atrium and ventricles, and
      trafficked beyond endothelial cell layers and between myocytes. CD45(+) cells
      localized at low incidence in the spleen, liver, lungs, and kidneys, but rarely
      remained in the circulation (<0.1% of infused cells). CONCLUSIONS: Coronary
      delivery of human CBMNCs during blood-cardioplegic arrest in a lamb model of CPB
      results in highly abundant myocardial distribution of cells without acute adverse
      effects on vascular patency and post-CPB cardiac function.

PMID- 26209486
TI  - Margin Distance Does Not Influence Recurrence and Survival After Wedge Resection
      for Lung Cancer.
AB  - BACKGROUND: The relationship between the free margin distance and the recurrence
      rate and overall survival after R0 wedge resection for non-small cell lung cancer
      (NSCLC) is still not clear. We retrospectively evaluated the long-term oncologic
      outcome of patients who had undergone wedge resection for NSCLC to assess the
      prognostic effect of margin distance in this setting. METHODS: Between 2003 and
      2013, 243 consecutive patients with a functional contraindication to major lung
      resection underwent wedge resection with systematic lymph node dissection for
      clinical stage I NSCLC. The study enrolled 182 patients with pathologic stage I
      and R0 resection and divided them into three subgroups according to margin
      distance of less than 1 cm (n = 30), 1 to 2 cm (n = 80), and more than 2 cm (n =
      72). RESULTS: The histologic assessment was adenocarcinoma in 112 patients,
      squamous cell in 30, and other in 40. Postoperative morbidity was 18.7%, and
      postoperative mortality was 1.1%. The median follow-up was 31 months (range, 2 to
      133 months). The locoregional (lung parenchyma, hilum, mediastinum) recurrence
      rate was 26.4% (n = 48). The distant recurrence rate was 11% (n = 20). Overall 5
      year survival was 70.4%. Disease-free 5-year survival was 51.7%. There was no
      statistical difference in locoregional (p = 0.9) and distant (p = 0.3) recurrence
      rate and no difference in overall survival (p = 0.07) when the three groups were
      compared. CONCLUSIONS: Wedge resection is a viable option for the surgical
      treatment of stage I NSCLC when lobectomy is contraindicated. The distance
      between the tumor and the parenchymal suture margin does not influence recurrence
      or the survival rate when an R0 resection is achieved.

PMID- 26209487
TI  - Outcomes of Thoracic Endovascular Aortic Repair in Acute Type B Aortic
      Dissection: Results From the Valiant United States Investigational Device
      Exemption Study.
AB  - BACKGROUND: Acute type B aortic dissection complicated by malperfusion or rupture
      carries a risk of death. We report 30-day and 12-month results of endovascular
      treatment with the Valiant Captivia Thoracic Stent Graft (Medtronic, Santa Rosa,
      CA) in patients with acute, complicated type B aortic dissection. METHODS: The
      Medtronic DISSECTION Trial is a prospective, nonrandomized, United States Food
      and Drug Administration-regulated, pivotal trial that enrolled patients at 16
      United States sites between June 2010 and May 2012. Follow-up examinations were
      at 1, 6, and 12 months, and annually through 5 years. RESULTS: Fifty patients
      were enrolled. Mean age was 57 years (range, 18 to 83 years). Rupture was present
      in 20% and malperfusion in 86%. Mean time from symptom onset to procedure was 4.7
      days (range, 0 to 23 days). Successful deployment and coverage of the primary
      entry tear was achieved in all patients. Two patients (4%) underwent open repair
      5 and 56 days postprocedure for retrograde aortic dissections. Thirty-day
      mortality was 8% (4 of 50) and 12-month mortality was 15% (7 of 48). Spinal
      ischemia was 6%. Serious adverse events occurred in 23 of 49 patients within 12
      months. Four patients underwent secondary endovascular procedures. Through 12
      months, true lumen diameter in the stented region remained stable or increased in
      93.1% (27 of 29) of patients. False lumen diameter remained stable or decreased
      in 22 patients and was partially or completely thrombosed in 91% (30 of 33).
      CONCLUSIONS: The initial results of the Valiant Thoracic Stent Graft in the
      treatment of acute type B aortic dissection are encouraging, but longer-term
      outcomes are needed.

PMID- 26209488
TI  - Increasing Frequency of Left Ventricular Assist Device Exchanges in the United
      States.
AB  - BACKGROUND: Recent reports indicate an increased prevalence and earlier onset of
      pump thrombosis and associated pump exchanges after left ventricular assist
      device (LVAD) implantation. Questions remain regarding the current rate and
      clinical effect of pump exchanges. METHODS: All United States Medicare fee-for
      service patients undergoing LVAD implantations (n = 3,166) between January 2009
      and December 2012 were identified by procedural codes present on carrier claims
      collected by the Centers for Medicare & Medicaid Services. Pump exchange, pump
      removal, heart transplantation, and death were collected from subsequent carrier
      claim and denominator files. Comorbidities present before implantation were
      generated using the Elixhauser comorbidity index. RESULTS: Compared with patients
      who received LVADs before March 1, 2011, LVAD recipients after March 1, 2011,
      were older on average (63.9 vs 62.2 years, p < 0.01), more likely to be male
      (82.3% vs. 79.4%, p = 0.04), and had a higher incidence of common comorbidities.
      The later cohort had higher occurrence of pump exchange by Kaplan-Meier time-to
      event estimates and Fisher exact tests at 3 months (1.8 vs 0.8, p = 0.02), 6
      months (3.3 vs 1.0, p < 0.01), and 12 months (4.9 vs 2.2, p < 0.01). Cox
      regression analysis found time-dependent pump exchange was associated with worse
      survival (hazard ratio, 2.5; 95% confidence interval, 1.8 to 3.62; p < 0.01)
      after adjusting for age, gender, and comorbidities. CONCLUSIONS: Although LVAD
      exchanges remain relatively uncommon, a significant increase in the incidence of
      the procedure has occurred since March 1, 2011. Pump exchanges are highly
      associated with death, and further research is required to understand the cause
      of this disturbing trend and surveillance to determine its trajectory.

PMID- 26209489
TI  - Red Blood Cell Transfusions Impact Pneumonia Rates After Coronary Artery Bypass
      Grafting.
AB  - BACKGROUND: Pneumonia, a known complication of coronary artery bypass grafting
      (CABG), significantly increases a patient's risk of morbidity and mortality.
      Although not well characterized, red blood cell (RBC) transfusions may increase a
      patient's risk of pneumonia. We describe the relationship between RBC transfusion
      and postoperative pneumonia after CABG. METHODS: A total of 16,182 consecutive
      patients underwent isolated CABG between 2011 and 2013 at 1 of 33 hospitals in
      the state of Michigan. We used multivariable logistic regression to estimate the
      relative odds of pneumonia associated with the use or number of RBC units (0, 1,
      2, 3, 4, 5, and >= 6). We adjusted for predicted risk of mortality, preoperative
      hematocrit values, history of pneumonia, cardiopulmonary bypass duration, and
      medical center. We confirmed the strength and direction of these relationships
      among selected clinical subgroups in a secondary analysis. RESULTS: Five hundred
      seventy-six (3.6%) patients had pneumonia and 6,451 (39.9%) received RBC
      transfusions. There was a significant association between any RBC transfusion and
      pneumonia (adjusted odds ratio [ORadj], 3.4; p < 0.001). There was a dose
      response between number of units and odds of pneumonia, with a ptrend less than
      0.001. Patients receiving only 2 units of RBCs had a 2-fold (ORadj, 2.1; p <
      0.001) increased odds of developing pneumonia. These findings were consistent
      across clinical subgroups. CONCLUSIONS: We found a significant volume-dependent
      association between an increasing number of RBCs and the odds of pneumonia, which
      persisted after risk adjustment. Clinical teams should explore opportunities for
      preventing a patient's risk of RBC transfusions, including reducing hemodilution
      or adopting a lower transfusion threshold in a stable patient.

PMID- 26209490
TI  - Contemporary Results of Aortic Coarctation Repair Through Left Thoracotomy.
AB  - BACKGROUND: Although surgical results for repair of coarctation of the aorta
      (CoA) have steadily improved, management of this condition remains controversial.
      The purposes of this study were to analyze the long-term outcomes of patients
      undergoing CoA repair through left thoracotomy and to define risk factors for
      reintervention. METHODS: All patients who were less than 18 years old and who
      underwent initial repair of CoA through left thoracotomy from 1995 to 2013 at
      Texas Children's Hospital (Houston, TX) were included. Patients were classified
      into 3 groups: 143 (42%) neonates (0 to 30 days old), 122 (36%) infants (31 days
      to 1 year old), and 78 (23%) older children (1 to 18 years old). Univariate and
      multivariate analyses were performed. RESULTS: A total of 343 patients (129 [38%]
      girls) with median age of 53 days (interquartile range [IQR],12 days to 9 months)
      and weight of 4.1 kg (IQR, 3.1 to 8.0) underwent repair with extended end-to-end
      anastomosis (291 patients [85%]), end-to-end anastomosis (44 patients [13%]),
      interposition graft (2 patients [0.6%]), or subclavian flap (6 patients [2%]).
      Concomitant diagnoses included genetic abnormalities (48 patients [14%]),
      isolated ventricular septal defects (58 patients [17%]), small left-sided
      structures (53 patients,16%), or other complex congenital heart disease (18
      patients [5%]). Perioperative mortality was 1% (n = 4, all neonates). At a median
      follow-up of 6 years (7 days to 19 years), only 14 (4%) patients required
      reintervention (10 catheter-based procedures, 6 surgical repairs). A
      postoperative peak velocity of 2.5 m/s or greater was an independent risk factor
      for reintervention (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.4 to
      11.6). Within the cohort, 95 (33%) patients were hypertensive or remained on
      cardiac medications a median of 12 years (6 months to 19 years) after the
      surgical procedure. Development of perioperative hypertension was associated with
      higher risk of chronic hypertension or cardiac medication dependency (OR, 1.9;
      95% CI, 1.1 to 3.3). CONCLUSIONS: CoA repair through left thoracotomy is
      associated with low rates of morbidity, mortality, and reintervention. Aortic
      arch obstruction should be completely relieved at the time of surgical
      intervention to minimize the risk of long-term recoarctation.

PMID- 26209491
TI  - Late Operating Room Start Times Impact Mortality and Cost for Nonemergent Cardiac
      Surgery.
AB  - BACKGROUND: There is growing concern over the effect of starting non-emergent
      cardiac surgery later in the day on clinical outcomes and resource utilization.
      Our objective was to determine the differences in patient outcomes for starting
      non-emergent cardiac surgery after 3 pm. METHODS: All non-emergent cardiac
      operations performed at a single institution from July 2008 to 2013 were
      reviewed. Cases were stratified based on "early start" or "late start," defined
      by incision time before or after 3 pm. Rates of observed and risk-adjusted
      mortality, major complications, and costs were compared on a univariate basis for
      all patients and by multivariable linear and logistic regression for patients
      with a valid The Society of Thoracic Surgeons (STS) Predicted Risk of Mortality
      (PROM). RESULTS: A total of 3,395 non-emergent cardiac operations were reviewed,
      including 368 late start cases. Compared with cases starting earlier, mortality
      was significantly higher for patients undergoing late operations (5.2% vs 3.5%, p
      = 0.046) despite similar preoperative risk (STS PROM 3.8% vs 3.3%) and major
      complication rates (18.2% vs 18.3%). Costs were 8% higher with late start cases
      ($51,576 vs $47,641, p < 0.001). After controlling for case type, surgeon, year,
      and risk, late cases resulted in higher mortality (odds ratio 2.04, p = 0.041)
      despite shorter operative duration (16 minutes, p < 0.001). CONCLUSIONS: Starting
      non-emergent cardiac cases later in the day is associated with 2 times higher
      absolute and risk-adjusted mortality. These data should be carefully considered,
      not only by surgeons and patients but also in the context of the operating room
      system when scheduling non-emergent cardiac cases.

PMID- 26209492
TI  - Long-Term Outcome of the Treatment of Zenker's Diverticulum.
AB  - BACKGROUND: Treatment of Zenker's diverticulum can be accomplished by use of a
      transcervical myotomy (TCM) with diverticulopexy/diverticulectomy or by the
      transoral endoscopic stapling (TOS) approach. Our aim was to evaluate the short
      term and long-term outcomes of these two techniques. METHODS: A retrospective
      review was performed to identify all patients who had received either treatment
      for Zenker's diverticulum from July 1998 to August 2013. Telephone interviews
      were attempted of all surviving patients to assess long-term outcome. RESULTS:
      There were 77 patients, with a median age of 71 years (range, 37 to 97 years).
      All patients had dysphagia, and 33 (43%) had regurgitation. TCM was performed in
      68 patients, and TOS was done in nine. The median size of the diverticulum was
      2.5 cm in the TCM group and 4 cm in the TOS group (p = 0.13). The operation was
      primary in 66 patients (86%) and a reoperation in 11 patients. The median
      hospital stay was 1 day for TOS and 3 for TCM (p = 0.0005). The median time to
      oral intake for both groups was 1 day. There were three adverse events in the TCM
      group and none in the TOS group. Early outcome was assessed in all 77 patients at
      a median of 4 months (interquartile range [IQR], 1 to 13.5 months). Symptomatic
      improvement occurred in all patients, with 55 patients (71%) reporting complete
      resolution. Long-term symptoms were assessed at a median of 54 months (IQR, 34 to
      77 months) in 38 of 59 (64%) surviving patients. CONCLUSIONS: Cricopharyngeal
      myotomy with diverticulopexy/diverticulectomy and TOS are both safe and effective
      treatments for Zenker's diverticulum. All patients reported improvement in
      symptoms, with complete resolution in the majority of patients.

PMID- 26209493
TI  - Surgical Outcomes in a Large, Clinical, Low-Dose Computed Tomographic Lung Cancer
      Screening Program.
AB  - BACKGROUND: Lung cancer screening with low-dose computed tomography is proven to
      reduce lung cancer mortality among high-risk patients. However, critics raise
      concern over the potential for unnecessary surgical procedures performed for
      benign disease as a result of screening. We reviewed our outcomes in a large
      clinical lung cancer screening program to assess the number of surgical
      procedures done for benign disease, as we believe this is an important quality
      metric. METHODS: We retrospectively reviewed our surgical outcomes of consecutive
      patients who underwent low-dose computed tomography lung cancer screening from
      January 2012 through June 2014 using a prospectively collected database. All
      patients met the National Comprehensive Cancer Network lung cancer screening
      guidelines high-risk criteria. RESULTS: There were 1,654 screened patients during
      the study interval with clinical follow-up at Lahey Hospital & Medical Center.
      Twenty-five of the 1,654 (1.5%) had surgery. Five of 25 had non-lung cancer
      diagnoses: 2 hamartomas, 2 necrotizing granulomas, and 1 breast cancer
      metastasis. The incidence of surgery for non-lung cancer diagnosis was 0.30% (5
      of 1,654), and the incidence of surgery for benign disease was 0.24% (4 of
      1,654). Twenty of 25 had lung cancer, 18 early stage and 2 late stage. There were
      no surgery-related deaths, and there was 1 major surgical complication (4%) at 30
      days. CONCLUSIONS: The incidence of surgical intervention for non-lung cancer
      diagnosis was low (0.30%) and is comparable to the rate reported in the National
      Lung Screening Trial (0.62%). Surgical intervention for benign disease was rare
      (0.24%) in our experience.

PMID- 26209494
TI  - Aortic Dissection in Patients With Bicuspid Aortic Valve-Associated Aneurysms.
AB  - BACKGROUND: Data regarding the risk of aortic dissection in patients with
      bicuspid aortic valve and large ascending aortic diameter are limited, and
      appropriate timing of prophylactic ascending aortic replacement lacks consensus.
      Thus our objectives were to determine the risk of aortic dissection based on
      initial cross-sectional imaging data and clinical variables and to isolate
      predictors of aortic intervention in those initially prescribed serial
      surveillance imaging. METHODS: From January 1995 to January 2014, 1,181 patients
      with bicuspid aortic valve underwent cross-sectional computed tomography (CT) or
      magnetic resonance imaging (MRI) to ascertain sinus or tubular ascending aortic
      diameter greater than or equal to 4.7 cm. Random Forest classification was used
      to identify risk factors for aortic dissection, and among patients undergoing
      surveillance, time-related analysis was used to identify risk factors for aortic
      intervention. RESULTS: Prevalence of type A dissection that was detected by
      imaging or was found at operation or on follow-up was 5.3% (n = 63). Probability
      of type A dissection increased gradually at a sinus diameter of 5.0 cm--from 4.1%
      to 13% at 7.2 cm--and then increased steeply at an ascending aortic diameter of
      5.3 cm--from 3.8% to 35% at 8.4 cm--corresponding to a cross-sectional area to
      height ratio of 10 cm(2)/m for sinuses of Valsalva and 13 cm(2)/m for the tubular
      ascending aorta. Cross-sectional area to height ratio was the best predictor of
      type A dissection (area under the curve [AUC] = 0.73). CONCLUSIONS: Early
      prophylactic ascending aortic replacement in patients with bicuspid aortic valve
      should be considered at high-volume aortic centers to reduce the high risk of
      preventable type A dissection in those with aortas larger than approximately 5.0
      cm or with a cross-sectional area to height ratio greater than approximately 10
      cm(2)/m.

PMID- 26209495
TI  - Impact of Ultrafiltration on Kidney Injury After Cardiac Surgery: The Michigan
      Experience.
AB  - BACKGROUND: This study examines the relationship between the use and volume of
      conventional ultrafiltration (CUF) and the risk of acute kidney injury (AKI)
      after isolated on-pump coronary artery bypass graft surgery. METHODS: A total of
      6,407 consecutive patients underwent isolated on-pump coronary artery bypass
      graft surgery between 2010 and 2013 at 21 medical centers participating in the
      PERFusion Measures and Outcomes (PERForm) registry. We assessed the effect of CUF
      use on AKI and other postoperative sequelae using a generalized linear mixed
      effect model with a logit link. We also modeled the effect of increasing volume
      of CUF per weight on AKI, and tested for any modification by a patient's
      preoperative kidney function. RESULTS: Patients having CUF were more likely to
      have diabetes, vascular disease, chronic obstructive pulmonary disease,
      congestive heart failure, history of a myocardial infarction, or an intraaortic
      balloon pump (p < 0.05). They had lower preoperative and nadir hematocrits,
      creatinine clearance, and ejection fraction (p < 0.05). Patients exposed to CUF
      had higher adjusted risk of AKI (adjusted odds ratio, 1.36; p = 0.002), although
      similar rates of death, stroke, and reoperation for bleeding (p > 0.05). The risk
      of AKI was modified by a patient's preoperative kidney function (p < 0.0004).
      Among patients with a creatinine clearance of less than 99.6 mL/min (95%
      confidence interval, 67.6 to 137.5), increasing volume of CUF was associated with
      a higher risk of AKI. CONCLUSIONS: Patients exposed to CUF had a higher adjusted
      risk of AKI. Clinical teams should consider lower volumes of CUF among patients
      with low creatinine clearance to minimize the risk of AKI.

PMID- 26209497
TI  - [Complications of BPH surgery: Evaluation of professional practices].

PMID- 26209496
TI  - Effectiveness of Surgical Ablation in Patients With Atrial Fibrillation and
      Aortic Valve Disease.
AB  - BACKGROUND: In patients with atrial fibrillation (AF), the addition of surgical
      ablation to aortic valve replacement (AVR) does not increase procedural morbidity
      or mortality. However, efficacy in this population has not been carefully
      evaluated. This study compared outcomes between patients undergoing stand-alone
      Cox-Maze IV with those undergoing surgical ablation and concomitant AVR. METHODS:
      From January 2002 to May 2014, 188 patients received a stand-alone Cox-Maze IV (n
      = 113) or surgical ablation with concomitant AVR (n = 75). In the concomitant AVR
      group, patients underwent Cox-Maze IV (n = 58), left-sided Cox-Maze IV (n = 3),
      or pulmonary vein isolation (n = 14). Thirty-one perioperative variables were
      compared. Freedoms from AF on and off antiarrhythmic drugs were evaluated at 3,
      6, 12, and 24 months. RESULTS: Follow-up was available in 97% of patients.
      Freedom from AF on and off antiarrhythmic drugs in patients receiving a stand
      alone Cox-Maze IV versus concomitant AVR was not significantly different at any
      time point. The concomitant AVR group had more comorbidities, paroxysmal AF,
      pacemaker implantations (24% vs 5%, p = 0.002), and complications (25% vs 5%, p <
      0.001). Freedoms from AF off antiarrhythmic drugs for patients receiving an AVR
      and pulmonary vein isolation at 1 year was only 50%, which was significantly
      lower than patients receiving an AVR and Cox-Maze IV ( 94%, p = 0.001).
      CONCLUSIONS: A Cox-Maze IV with concomitant AVR is as effective as a stand-alone
      Cox-Maze IV in treating AF, even in an older population with more comorbidities.
      Pulmonary vein isolation was not as effective and is not recommended in this
      population. A Cox-Maze IV should be considered in all patients undergoing AVR
      with a history of AF.

PMID- 26209498
TI  - [The role of chemotherapy in bladder cancer].
AB  - The management of bladder cancer, initially exclusively surgical, was recently
      improved by the development of chemotherapy. Chemotherapy can thus be proposed as
      bladder instillations in order to prevent recurrences of non-muscle-invasive
      cancer (NMIC), and systemically in case of muscle-invasive cancer (MIC).
      Chemotherapy can then be administered prior to surgery (neoadjuvant), as a
      complement to surgery (adjuvant), as an alternative to surgery as part of a
      multimodality treatment, and alone in palliative intent in case of metastatic
      cancer. Renal function and general health status of the patient help the decision
      making and the choice of the chemotherapy regimen, which should be validated
      during a multidisciplinary meeting and presented to the patient during a
      dedicated medical and paramedical appointment. 

PMID- 26209499
TI  - Depressive behavior induced by social isolation of predisposed female rats.
AB  - Depression is a mood disorder that is more prevalent in women and has been
      closely associated with chronic stress. Many models of depression have been
      suggested that consider different forms of stress. In fact, stress is present in
      the life of every human being, but only a few develop depression. Accordingly, it
      seems wrong to consider all stressed animals to be depressed, emphasizing the
      importance of predisposition for this mood disorder. Based on this finding, we
      evaluated a predisposition to depressive behavior of female rats on the forced
      swim test (FST), and the more immobile the animal was during the FST, the more
      predisposed to depression it was considered to be. Then, animals were subjected
      to the stress of social isolation for 21 days and were re-evaluated by the FST.
      The Predisposed/Isolated rats presented higher immobility times. Once all the
      rats had prior experience in the FST, we calculated an Index of Increase by
      Isolation, confirming the previous results. Based on this result, we considered
      the Predisposed/Isolated group as presenting depressive behavior ('Depressed')
      and the Nonpredisposed/Nonisolated group as the control group ('Nondepressed').
      The animals were distributed into 4 new groups: Nondepressed/Vehicle,
      Nondepressed/Amitriptyline, Depressed/Vehicle, Depressed/Amitriptyline. After 21
      days of treatment, only the Depressed/Vehicle group differed from the other 3
      groups, demonstrating the efficacy of amitriptyline in treating the depressive
      behavior of the Depressed animals, validating the model. This study shows that
      conducting an FST prior to any manipulation can predict predisposition to
      depressive behavior in female rats and that the social isolation of predisposed
      animals for 21 days is effective in inducing depressive behavior. This behavior
      can be considered real depressive behavior because it takes into account
      predisposition, chronic mild stress, and the prevalent gender.

PMID- 26209500
TI  - Soluble CD163 is increased in patients with acute pancreatitis independent of
      disease severity.
AB  - Macrophages are crucially involved in the pathophysiology of acute pancreatitis.
      Soluble CD163 (sCD163) is specifically released from macrophages and systemic
      levels are increased in inflammatory diseases. Here, sCD163 was measured in serum
      of 50 patients with acute pancreatitis to find out possible associations with
      disease activity. Admission levels of systemic sCD163 were nearly three-fold
      higher in patients with acute pancreatitis compared to controls. In patients
      sCD163 did not correlate with C-reactive protein and leukocyte count as
      established markers of inflammation. Levels were not associated with disease
      severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age,
      and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis
      score. Soluble CD163 was not related to complications of acute pancreatitis.
      These data show that serum sCD163 is increased in acute pancreatitis indicating
      activation of macrophages but is not associated with disease severity and
      outcome. 

PMID- 26209501
TI  - KPNA2 interacts with P65 to modulate catabolic events in osteoarthritis.
AB  - OBJECTIVE: Karyopherin alpha 2 (KPNA2) is a member of the importin alpha family,
      which acts as an adaptor to deliver P65 to the nucleus by recognizing the classic
      nuclear localization signal (NLS) of the cargo protein, and which has been
      reported as being involved in the pathogenesis of many diseases. This study was
      undertaken to determine the expression and possible functions of KPNA2 in
      osteoarthritis (OA). METHODS: KPNA2 expression in cartilage tissues of OA
      patients and normal controls was detected by RT-PCR and immunohistochemistry.
      SW1353 cells were stimulated with IL-1beta to establish the chondrocyte injury
      model in vitro. The expression of KPNA2 and catabolic genes in IL-1beta-treated
      SW1353 cells were determined by Western blot. The interaction between KPNA2 and
      P65 was analyzed by co-immunoprecipitation, the subcellular distribution and
      transportation of P65 were detected by the subcellular fractionation followed by
      immunoblot analysis and immunofluorescence. Furthermore, we used RNA interference
      to analyze the role of KPNA2 in IL-1beta-induced P65 nuclear importation and
      MMP13, ADAMTS-5 expression in SW1353 cells. RESULTS: Cartilage expression of
      KPNA2 was higher in patients with OA compared with normal controls and mainly
      locating in chondrocytes. In IL-1beta-treated SW1353 cells, up-regulation of
      KPNA2 was accompanied by the elevated expression of the catabolic marker protein
      levels, including MMP13 and ADAMTS-5, and increased NF-kappaB P65 nuclear
      importation. Knock-down of KPNA2 resulted in decreased catabolic marker protein
      levels in IL-1beta-treated SW1353 cells. KPNA2 interacted with p65, and loss of
      KPNA2 caused decreased nuclear translocation of the active p50/p65 NF-kappaB
      complex. CONCLUSIONS: These findings suggested that KPNA2 may promote NF-kappaB
      activation via facilitating P65 nuclear transportation, and thus subsequently
      accelerate the catabolic events of osteoarthritis.

PMID- 26209503
TI  - Transcriptional regulation of the VEGF gene in dependence of individual genomic
      variations.
AB  - Overexpression of the vascular endothelial growth factor (VEGF) gene has been
      associated with advanced stage and poor survival in several cancers. The majority
      of disease-associated VEGF-single nucleotide polymorphisms (SNPs) locate within
      regulatory regions. Therefore, an influence of SNPs located in the promoter/5'
      untranslated region (5'UTR) on transcription factor binding (TFB) and gene
      expression seems feasible. We reviewed the literature investigating a potential
      connection of VEGF-SNPs and transcriptional regulation of the VEGF gene. In
      addition, we employed transcription factor databases to search for VEGF-SNPs
      which have already been associated with diseases. The objective of this review is
      to gain an overview about an association of VEGF-SNPs and the transcription
      factor dependent regulation of the VEGF gene. A decreasing binding specificity of
      the transcription factor MZF1 in presence of the VEGF-SNP +405 C-allele has been
      reported. TF databases indicated a potential HIF binding site for the -2578 C
      allele representing an important potential inducer of VEGF expression.
      Additionally, linkage disequilibrium of the -2578 A-allele and an 18 bp insertion
      increases the number of potential TFB sites. For the VEGF promoter SNP -1154 A/G
      an interaction with the HRE under participation of the SNP +405 C/G was supposed.
      The comprehension of the association of specific SNPs and TFB could be an
      essential part in our understanding of individual differences of VEGF regulation
      and course of diseases.

PMID- 26209504
TI  - The resolution of inflammation: New mechanisms in patho-physiology open
      opportunities for pharmacology.

PMID- 26209502
TI  - A Phase 3 Trial of 2 Years of Androgen Suppression and Radiation Therapy With or
      Without Adjuvant Chemotherapy for High-Risk Prostate Cancer: Final Results of
      Radiation Therapy Oncology Group Phase 3 Randomized Trial NRG Oncology RTOG 9902.
AB  - PURPOSE: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is
      a standard treatment of high-risk, localized prostate cancer (PCa). Radiation
      Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that
      adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral
      etoposide plus LT AS plus RT would improve overall survival (OS). METHODS AND
      MATERIALS: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL
      and Gleason score [GS] >= 7 or clinical stage >= T2 and GS >= 8) were randomized
      to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was given as
      four 21-day cycles, delivered beginning 28 days after 70.2 Gy of RT. AS was given
      as luteinizing hormone-releasing hormone for 24 months, beginning 2 months before
      RT plus an oral antiandrogen for 4 months before and during RT. The study was
      designed based on a 6% improvement in OS from 79% to 85% at 5 years, with 90%
      power and a 2-sided alpha of 0.05. RESULTS: A total of 397 patients (380
      eligible) were randomized. The patients had high-risk PCa, 68% with GS 8 to 10
      and 34% T3 to T4 tumors, and median prostate-specific antigen of 22.6 ng/mL. The
      median follow-up period was 9.2 years. The trial closed early because of excess
      thromboembolic toxicity in the CT arm. The 10-year results for all randomized
      patients revealed no significant difference between the AS + RT and AS + RT + CT
      arms in OS (65% vs 63%; P=.81), biochemical failure (58% vs 54%; P=.82), local
      progression (11% vs 7%; P=.09), distant metastases (16% vs 14%; P=.42), or
      disease-free survival (22% vs 26%; P=.61). CONCLUSIONS: NRG Oncology RTOG 9902
      showed no significant differences in OS, biochemical failure, local progression,
      distant metastases, or disease-free survival with the addition of adjuvant CT to
      LT AS + RT. The trial results provide valuable data regarding the natural history
      of high-risk PCa treated with LT AS + RT and have implications for the
      feasibility of clinical trial accrual and tolerability using CT for PCa.

PMID- 26209505
TI  - NICE guidance on nintedanib for previously treated locally advanced, metastatic,
      or locally recurrent non-small-cell lung cancer.

PMID- 26209506
TI  - [Infantile haemangioma: When investigation is necessary and current therapeutic
      developments].
AB  - Infantile haemangioma (IH) is the most frequent benign tumour seen in children.
      In most cases, diagnosis is made chiefly on clinical grounds, and because the
      condition tends to subside naturally within several years and without any major
      sequelae, therapeutic abstention is the rule. However, a number of additional
      investigations may be necessary: where the clinical picture is atypical or
      potentially confusing, where the condition may affect adjacent or remote
      structures, in screening for associated anomalies in certain syndromal forms
      which practitioners must be able to recognise. Such investigations facilitate
      therapeutic indications for forms of haemangioma likely to lead to complications.
      The most important recent therapeutic development has been the discovery of the
      spectacular efficacy of beta-blockers (propranolol) upon the development kinetics
      of infantile haemangioma, greatly transforming the prognosis for these
      haemangiomas at risk. 

PMID- 26209507
TI  - Complete genome sequence of a keratin-degrading bacterium Chryseobacterium
      gallinarum strain DSM 27622(T) isolated from chicken.
AB  - Chryseobacterium gallinarum strain DSM 27622(T) is a keratin-degrading bacterium
      belonging to the class Flavobacteriia, which was isolated from chicken. Here, we
      report the 4633,632bp complete genome sequence of the strain DSM 27622(T) with
      4161 genes. 

PMID- 26209508
TI  - Has growth in electronic cigarette use by smokers been responsible for the
      decline in use of licensed nicotine products? Findings from repeated cross
      sectional surveys.
AB  - BACKGROUND: The rise in electronic cigarette use by smokers may be responsible
      for the decreased use of licensed nicotine products and/or increased overall use
      of non-tobacco nicotine-containing products. This paper reports findings from the
      Smoking Toolkit Study (STS) tracking use of electronic cigarettes and licensed
      nicotine products to address this issue. METHODS: Data were obtained from monthly
      surveys involving 14 502 cigarette smokers in England between March 2011 and
      November 2014. Smokers were asked about their use of electronic cigarettes and
      licensed nicotine products. RESULTS: Prevalence of electronic cigarette use
      increased rapidly from 2.2% (95% CI 1.4% to 3.2%) in quarter 2 of 2011 to 20.8%
      (95% CI 18.3% to 23.4%) in quarter 3 of 2013, after which there was no change.
      Prevalence of licensed nicotine product use in smokers remained stable from
      quarter 2 of 2011 (17.4%, 95% CI 15.3% to 19.8%) to quarter 3 of 2013 (17.9%, 95%
      CI 15.62% to 20.5%), and thereafter declined steadily to 7.9% (95% CI 6.0% to
      10.4%). Prevalence of use of any product was stable to quarter 1 of 2012, after
      which it increased from 18.5% (95% CI 16.3% to 21.0%) to 33.3% (95% CI 30.4% to
      36.3%) in quarter 3 of 2013, and then decreased to 22.7% (95% CI 19.3% to 26.3%).
      CONCLUSIONS: The shapes of trajectories since 2011 suggest that electronic
      cigarettes are probably not responsible for the decline in use of licensed
      nicotine products. Electronic cigarettes appear to have increased the total
      market for use of non-tobacco nicotine-containing products.

PMID- 26209510
TI  - Apple MdACS6 Regulates Ethylene Biosynthesis During Fruit Development Involving
      Ethylene-Responsive Factor.
AB  - Ethylene biosynthesis in plants involves different 1-aminocyclopropane-1
      carboxylic acid synthase (ACS) genes. The regulation of each ACS gene during
      fruit development is unclear. Here, we characterized another apple
      (Malus*domestica) ACS gene, MdACS6. The transcript of MdACS6 was observed not
      only in fruits but also in other tissues. During fruit development, MdACS6 was
      initiated at a much earlier stage, whereas MdACS3a and MdACS1 began to be
      expressed at 35 d before harvest and immediateley after harvest, respectively.
      Moreover, the enzyme activity of MdACS6 was significantly lower than that of
      MdACS3a and MdACS1, accounting for the low ethylene biosynthesis in young fruits.
      Overexpression of MdACS6 (MdACS6-OE) by transient assay in apple showed enhanced
      ethylene production, and MdACS3a was induced in MdACS6-OE fruits but not in
      control fruits. In MdACS6 apple fruits silenced by the virus-induced gene
      silencing (VIGS) system (MdACS6-AN), neither ethylene production nor MdACS3a
      transcript was detectable. In order to explore the mechanism through which
      MdACS3a was induced in MdACS6-OE fruits, we investigated the expression of apple
      ethylene-responsive factor (ERF) genes. The results showed that the expression of
      MdERF2 was induced in MdACS6-OE fruits and inhibited in MdACS6-AN fruits. Yeast
      one-hybrid assay showed that MdERF2 protein could bind to the promoter of
      MdACS3a. Moreover, down-regulation of MdERF2 in apple flesh callus led to a
      decrease of MdACS3a expression, demonstrating the regulation of MdERF2 on
      MdACS3a. The mechanism through which MdACS6 regulates the action of MdACS3a was
      discussed. 

PMID- 26209511
TI  - The Factor Structure and Construct Validity of the Short Version of the Youth
      Psychopathic Traits Inventory in Two Independent Samples of Nonreferred
      Adolescents.
AB  - To assess the internal consistency, factor structure, and construct validity of
      the Italian translation of the Youth Psychopathic Traits Inventory-Short Version
      (YPI-S), both the YPI-S and its full version, the YPI, as well as self-reports of
      delinquency, aggression, and Big Five domains, were administered to two
      independent samples (N = 868 and N = 881) of Italian community, nonreferred
      adolescents. The internal consistency of the YPI-S was adequate, and confirmatory
      factor analyses showed a good fit of the theoretical three-factor model of the
      YPI-S in both samples. Hierarchical regression models suggested the same pattern
      of associations with self-report measures of delinquency and aggression for the
      YPI-S and YPI, although the YPI was a better predictor of Big Five domains than
      the YPI-S. The findings support the internal consistency, factor validity, and
      construct validity of the YPI-S.

PMID- 26209512
TI  - Rasch Validation and Cross-Validation of the Health of Nation Outcome Scales for
      Monitoring of Psychiatric Disability in Traumatized Refugees in Western
      Psychiatric Care.
AB  - There are no validated measures of psychiatric disability for traumatized
      refugees in Western psychiatric care. This is a serious shortcoming as it
      precludes monitoring of global treatment outcomes in this group, as well as
      appropriate matching of treatment needs to the disability levels. Using Rasch
      analysis, we evaluated the psychometrics of the Health of Nation Outcome Scales
      (HoNOS) in pretreatment data of consecutive refugee patients (N = 448) from a
      Danish psychiatric clinic. Then, we carried out a cross-validation of the
      pretreatment HoNOS model on posttreatment data from the same group. A revised 10
      item HoNOS fit the Rasch model at pretreatment and also showed excellent fit
      within the cross-validation data. Culture, gender, and need for translation did
      not exert serious bias on the measure's performance. The results establish good
      monitoring properties of the 10-item HoNOS as the first validated measure of
      psychiatric disability for traumatized refugees in Western psychiatric care.

PMID- 26209513
TI  - Development of a 12-Item Abbreviated Three-Dimensional Wisdom Scale (3D-WS-12):
      Item Selection and Psychometric Properties.
AB  - Wisdom has been reported to be associated with better mental health and quality
      of life among older adults. Over the past decades, there has been considerable
      growth in empirical research on wisdom, including the development of standardized
      measures. The 39-item Three-Dimensional Wisdom Scale (3D-WS) is a useful
      assessment tool, given its rigorous development and good psychometric properties.
      However, the measure's length can prohibit use. In this article, we used a sample
      of 1,546 community-dwelling adults aged 21 to 100 years (M = 66 years) from the
      Successful AGing Evaluation (SAGE) study to develop an abbreviated 12-item
      version of the 3D-WS: the 3D-WS-12. Balancing concerns for measurement precision,
      internal structure, and content validity, factor analytic methods and expert
      judgment were used to identify a subset of 12-items for the 3D-WS-12. Results
      suggest that the 3D-WS-12 can provide efficient and valid assessments of Wisdom
      within the context of epidemiological surveys.

PMID- 26209514
TI  - Discrepancies in assessing home care workers' working conditions in a Norwegian
      home care service: differing views of stakeholders at three organizational
      levels.
AB  - BACKGROUND: The present study is a follow-up study of factors contributing to an
      undesirable quality of work environment and sick leave rate in the home care
      services in a Norwegian municipality. The underlying assumption is that
      organizational discrepancies in the perceptions and appraisals of significant
      factors and processes in an organization have detrimental effects on the
      management of the organization and on work environment conditions. Thus, the
      study aim is to explore potential organizational discrepancies in the appraisals
      of factors relating to home care workers' working conditions. METHODS: The study,
      using a mixed-methods design, comprised six home care units. It included survey
      responses of home care workers (80 respondents, response rate 54 %) and
      qualitative descriptions of stakeholders' appraisals of organizational issues
      gathered through semi-structured interviews (33 interviews with stakeholders at
      three organizational levels). RESULTS: Employees at different organizational
      levels in the home care services expressed divergent appraisals of factors
      related to the working conditions of home care workers, including impact of
      organizational measures (i.e. time pressure, work tasks, a new work program,
      organizational changes, budget model, budget allocation and coping strategies).
      Survey responses supported interview descriptions by home care workers. Results
      suggest that organizational discrepancy serve as an important barrier to a
      sustainable, well-functioning organization in general and to quality-enhancing
      changes to work procedures in particular. CONCLUSIONS: It is recommended to
      improve communication channels and facilitate the exchange of information across
      levels to ensure a common understanding of matters significant to the
      organization of the home care services and to the work environment of home care
      workers. The prevalence and impact of organizational discrepancy should be
      included in organization research, particularly when exploring explanatory
      factors of an unhealthy organization.

PMID- 26209515
TI  - Effects of sulfamethoxazole-trimethoprim associated to resveratrol on its free
      form and complexed with 2-hydroxypropyl-beta-cyclodextrin on cytokines levels of
      mice infected by Toxoplasma gondii.
AB  - The aim of this study was to investigate the effects of resveratrol on its free
      form and complexed with 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) when
      associated with sulfamethoxazole-trimethoprim (ST) on cytokines levels of mice (n
      = 60) experimentally infected by Toxoplasma gondii. Groups A and E were used as
      controls (untreated): negative and positive, respectively. The onset of treatment
      started 20 days post-infection (PI), and it lasted for 10 consecutive days. ST
      was administered orally in doses of 0.5 mg kg(-1) for groups B and F, while 100
      mg kg(-1) was the dose for resveratrol in its free form (groups C - G), inclusion
      complex (groups D and H), and on free and inclusion complex together (groups I -
      J). On day 31 PI, blood samples were collected in order to evaluate the cytokine
      profile. The mice that received drug combination (I and J) showed a significant
      (P < 0.05) reduction in the number of cysts in the brain compared to other
      infected groups (E - H). The results showed that mice from the Group E had
      increased (P < 0.001) levels of pro-inflammatory cytokines, while IL-10 levels
      were reduced when compared to the Group A. Additionally, there were increased
      levels of IL-4 and IFN-gamma in animals of groups C and D, respectively (P <
      0.05). Animals of the Group B showed reduced levels of IL-1, IL-4, IL-6, TNF
      alpha, and IFN-gamma (P < 0.05). Mice infected and treated (groups F - J) showed
      increased levels of pro-inflammatory cytokines along with a reduction of IL-10.
      Treatment with the combination of drugs (the Group J) led to a protective effect,
      i.e. reduction in pro-inflammatory cytokines. Therefore, resveratrol associated
      with ST was able to modulate seric cytokine profile and moderate the tissue
      inflammatory process caused by T. gondii infection, as well as to reduce parasite
      multiplication.

PMID- 26209516
TI  - Photodynamic therapy versus anti-vascular endothelial growth factor agents for
      polypoidal choroidal vasculopathy: a meta-analysis.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability
      of photodynamic therapy (PDT) compared to intravitreal vascular endothelial
      growth factor (VEGF) inhibitors in the treatment of polypoidal choroidal
      vasculopathy (PCV). METHODS: Relevant studies were selected through an extensive
      search of the PubMed, EMBASE, Web of Science, and Cochrane Library databases.
      Outcomes of interest included visual outcomes, anatomic variables, and adverse
      events. RESULTS: Six studies enrolling a total of 346 patients were included. The
      weighted mean differences (WMDs) of the mean changes in LogMAR VA when comparing
      PDT with anti-VEGF were -0.02 (95 % confidence interval [CI]: -0.12-0.08) at 3
      months, 0.02 (95 % CI: -0.12-0.16) at 6 months, 0.02 (95 % CI: -0.15-0.18) at 12
      months, and -0.17 (95 % CI: -0.90-0.55) at 24 months. There were no significant
      differences between the two groups at any of the time points. PDT was found to be
      associated with greater reduction of central retinal thickness (CRT) at six
      months (WMD: 44.94; 95 % CI: 16.44-73.44; P = 0.002), and it was superior to anti
      VEGF therapy in achieving complete polyp regression (odd ratio, OR: 6.85; 95 %
      CI: 2.15-21.79; P = 0.001).Rates of adverse events did not differ significantly
      between the two treatments. CONCLUSIONS: PDT appeared to result in greater CRT
      reduction at six months and higher polyp regression rate. However, the two
      treatments appear to be comparable in terms of best corrected visual acuity
      change and adverse events.

PMID- 26209509
TI  - Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric
      Network Associated with Serous Ovarian Cancer Risk.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci
      associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that
      some of these loci function through nearby transcription factor (TF) genes and
      that putative target genes of these TFs as identified by coexpression may also be
      enriched for additional EOC risk associations. METHODS: We selected TF genes
      within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual
      information, a form of correlation, was used to build networks of genes strongly
      coexpressed with each selected TF gene in the unified microarray dataset of 489
      serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset
      were subsequently ranked using a gene-level test based on results for germline
      SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). RESULTS:
      Gene set enrichment analysis identified six networks centered on TF genes (HOXB2,
      HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly
      enriched for genes from the risk-associated end of the ranked list (P < 0.05 and
      FDR < 0.05). These results were replicated (P < 0.05) using an independent
      association study (7,035 cases/21,693 controls). Genes underlying enrichment in
      the six networks were pooled into a combined network. CONCLUSION: We identified a
      HOX-centric network associated with serous EOC risk containing several genes with
      known or emerging roles in serous EOC development. IMPACT: Network analysis
      integrating large, context-specific datasets has the potential to offer
      mechanistic insights into cancer susceptibility and prioritize genes for
      experimental characterization.

PMID- 26209517
TI  - Trabecular bone loss in collagen antibody-induced arthritis.
AB  - INTRODUCTION: Postmenopausal women with rheumatoid arthritis (RA) have increased
      risk of developing osteoporosis due to chronic inflammation and estrogen
      deprivation. Collagen antibody-induced arthritis (CAIA), an experimental
      polyarthritis model representing the effector phase of arthritis, is mainly
      mediated by the innate immune system. Compared to the widely used collagen
      induced arthritis model, CAIA is conveniently short and can be used in C57BL/6
      mice, enabling studies with knock-out mice. However, the impact on bone of the
      CAIA model in C57BL/6 mice has not previously been studied. Therefore, the aim of
      this study was to determine if CAIA can be used to study postmenopausal arthritis
      induced osteoporosis. METHODS: CAIA was induced by administration of collagen
      type II antibodies and lipopolysaccharide to ovariectomized female C57BL/6J mice.
      Control mice received lipopolysaccharide, but no antibodies. Nine days later,
      femurs were collected for high-resolution micro-CT and histomorphometry. Serum
      was used to assess cartilage breakdown and levels of complement. Frequencies of
      immune cell subsets from bone marrow and lymph nodes were analyzed by flow
      cytometery. RESULTS: Trabecular bone mass was decreased and associated with
      increased number of osteoclasts per bone surface in the CAIA model. Also, the
      frequency of interleukin-17(+) cells in lymph nodes was increased in CAIA.
      CONCLUSION: The present study show that CAIA, a short reproducible arthritis
      model that is compatible with C57BL/6 mice, is associated with increased number
      of osteoclasts and trabecular bone loss.

PMID- 26209518
TI  - Phylogenetic and recombination analysis of Tobacco bushy top virus in China.
AB  - BACKGROUND: During the past decade, tobacco bushy top disease, which is mainly
      caused by a combination of Tobacco bushy top virus (TBTV) and Tobacco vein
      distorting virus (TVDV), underwent a sudden appearance, extreme virulence and
      degeneration of the epidemic in the Yunnan province of China. In addition to
      integrative control of its aphid vector, it is of interest to examine diversity
      and evolution among different TBTV isolates. METHODS: 5' and 3' RACE, combined
      with one step full-length RT-PCR, were used to clone the full-length genome of
      three new isolates of TBTV that exhibited mild pathogenicity in Chinese fields.
      Nucleotide and amino acid sequences for the TBTV isolates were analyzed by
      DNAMAN. MEGA 5.0 was used to construct phylogenetic trees. RDP4 was used to
      detect recombination events during evolution of these isolates. RESULTS: The
      genomes of three isolates, termed TBTV-JC, TBTV-MD-I and TBTV-MD-II, were 4152 nt
      in length and included one distinctive difference from previously reported TBTV
      isolates: the first nucleotide of the genome was a guanylate instead of an
      adenylate. Diversity and phylogenetic analyses among these three new TBTV
      isolates and five other available isolates suggest that ORFs and 3'UTRs of TBTV
      may have evolved separately. Moreover, the RdRp-coding region was the most
      variable. Recombination analysis detected a total of 29 recombination events in
      the 8 TBTV isolates, in which 24 events are highly likely and 5 events have low
      level likelihood based on their correlation with the phylogenetic trees. The
      three new TBTV isolates have individual recombination patterns with subtle
      divergences in parents and locations. CONCLUSIONS: The genome sizes of TBTV
      isolates were constant while different ORF-coding regions and 3'UTRs may have
      evolved separately. The RdRp-coding region was the most variable. Frequent
      recombination occurred among TBTV isolates. Three new TBTV isolates have
      individual recombination patterns and may have different progenitors.

PMID- 26209519
TI  - Molecular epidemiology and phylogenetic analysis of Hepatitis B virus in a group
      of migrants in Italy.
AB  - BACKGROUND: Hepatitis B virus infection (HBV) is widespread and it is considered
      a major health problem worldwide. The global distribution of HBV varies
      significantly between countries and between regions of the world. Among the many
      factors contributing to the changing epidemiology of viral hepatitis, the
      movement of people within and between countries is a potentially important one.
      In Italy, the number of migrant individuals has been increasing during the past
      25 years. HBV genotype D has been found throughout the world, although its
      highest prevalence is in the Mediterranean area, the Middle East and southern
      Asia. We describe the molecular epidemiology of HBV in a chronically infected
      population of migrants (living in Italy), by using the phylogenetic analysis.
      METHODS: HBV-DNA was amplified and sequenced from 43 HBV chronically infected
      patients. Phylogenetic and evolutionary analysis were performed using both
      maximum Likelihood and Bayesian methods. RESULTS AND CONCLUSION: Of the 43 HBV S
      gene isolates from migrants, 25 (58.1 %) were classified as D genotype. Maximum
      Likelihood analysis showed an intermixing between Moldavian and foreigners
      sequences mostly respect to Italian ones. Italian sequences clustered mostly
      together in a main clade separately from all others. The estimation of the time
      of the tree's root gave a mean value of 17 years ago, suggesting the origin of
      the tree back to 1992 year. The skyline plot showed that the number of infections
      softly increased until the early 2005s, after which reached a plateau. Comparing
      phylogenetic data to the migrants date of arrival in Italy, it should be possible
      that migrants arrived in Italy yet infected from their country of origin. In
      conclusion, this is the first paper where phylogenetic analysis and genetic
      evolution has been used to characterize HBV sub genotypes D1 circulation in a
      selected and homogenous group of migrants coming from a restricted area of
      Balkans and to approximately define the period of infection besides the migration
      date.

PMID- 26209520
TI  - Regulation of ERK-MAPK signaling in human epidermis.
AB  - BACKGROUND: The skin is largely comprised of keratinocytes within the
      interfollicular epidermis. Over approximately two weeks these cells differentiate
      and traverse the thickness of the skin. The stage of differentiation is therefore
      reflected in the positions of cells within the tissue, providing a convenient
      axis along which to study the signaling events that occur in situ during
      keratinocyte terminal differentiation, over this extended two-week timescale. The
      canonical ERK-MAPK signaling cascade (Raf-1, MEK-1/2 and ERK-1/2) has been
      implicated in controlling diverse cellular behaviors, including proliferation and
      differentiation. While the molecular interactions involved in signal transduction
      through this cascade have been well characterized in cell culture experiments,
      our understanding of how this sequence of events unfolds to determine cell fate
      within a homeostatic tissue environment has not been fully characterized.
      METHODS: We measured the abundance of total and phosphorylated ERK-MAPK signaling
      proteins within interfollicular keratinocytes in transverse cross-sections of
      human epidermis using immunofluorescence microscopy. To investigate these data we
      developed a mathematical model of the signaling cascade using a normalized-Hill
      differential equation formalism. RESULTS: These data show coordinated variation
      in the abundance of phosphorylated ERK-MAPK components across the epidermis.
      Statistical analysis of these data shows that associations between phosphorylated
      ERK-MAPK components which correspond to canonical molecular interactions are
      dependent upon spatial position within the epidermis. The model demonstrates that
      the spatial profile of activation for ERK-MAPK signaling components across the
      epidermis may be maintained in a cell-autonomous fashion by an underlying spatial
      gradient in calcium signaling. CONCLUSIONS: Our data demonstrate an extended
      phospho-protein profile of ERK-MAPK signaling cascade components across the
      epidermis in situ, and statistical associations in these data indicate canonical
      ERK-MAPK interactions underlie this spatial profile of ERK-MAPK activation. Using
      mathematical modelling we have demonstrated that spatially varying calcium
      signaling components across the epidermis may be sufficient to maintain the
      spatial profile of ERK-MAPK signaling cascade components in a cell-autonomous
      manner. These findings may have significant implications for the wide range of
      cancer drugs which therapeutically target ERK-MAPK signaling components.

PMID- 26209521
TI  - Low concentrations of serum testosterone predict acute myocardial infarction in
      men with type 2 diabetes mellitus.
AB  - BACKGROUND: The aim of the present study was to investigate the associations
      between endogenous testosterone concentrations and the incidence of acute
      myocardial infarction (AMI) in men and women with and without type 2 diabetes.
      METHODS: The study comprised 1109 subjects >=40 years of age (mean age 62 +/- 12
      years) participating in a baseline survey in Sweden in 1993-94. Information about
      smoking habits and physical activity was obtained using validated questionnaires.
      Serum concentrations of testosterone and sex hormone-binding globulin (SHBG) were
      obtained using radioimmunoassay. Diagnosis of type 2 diabetes was based on WHO's
      1985 criteria. Individual patient information on incident AMI was ascertained by
      record linkage with national inpatient and mortality registers from baseline
      through 2011. RESULTS: The prevalence of type 2 diabetes at baseline was 10.0% in
      men and 7.5% in women. During a mean follow-up of 14.1 years (+/-5.3), there were
      74 events of AMI in men and 58 in women. In age-adjusted Cox models, a
      significant inverse association between concentrations of testosterone and AMI
      morbidity was found in men with type 2 diabetes (HR = 0.86 CI (0.75-0.98)). In a
      final model also including waist-to-hip ratio, systolic blood pressure, total
      cholesterol and active smoking, the association still remained statistically
      significant (HR = 0.754 CI (0.61-0.92)). CONCLUSION: Low concentrations of
      testosterone predicted AMI in men with type 2 diabetes independent of other risk
      factors. Trials with testosterone investigating the effect regarding
      cardiovascular outcome are still lacking. Future trials in this field should take
      into account a modification effect of diabetes.

PMID- 26209522
TI  - Possibility of determining the degree of adhesion of the lymph node to the
      pulmonary artery preoperatively.
AB  - BACKGROUND: To make a preoperative determination of the degree of adhesion of the
      lymph node (LN) to the pulmonary artery (PA) in patients with lung cancer.
      METHODS: We investigated clinical parameters, including sex, age, smoking, stage,
      histology and surgical procedure, and performed an image analysis using CT
      scanning. RESULTS: The data for sex, age, smoking, stage, histology and the
      surgical procedure were identical between the "adhesion" and "no adhesion"
      groups. However, three of the five analyzable cases in the adhesion group clearly
      showed the disappearance of the fat plane on minimum intensity projection (minIP)
      computed tomography (CT). In particular, sites on more than three slices
      demonstrated the disappearance of the fat plane. On the other hand, five of the
      eight analyzable cases in the no adhesion group showed no disappearance of the
      fat plane. Therefore, one central slice adequately reflected the fat plane in the
      cases in the no adhesion group. CONCLUSIONS: These findings suggest that it is
      necessary to obtain a careful diagnosis of the extent of attachment of the LN to
      the PA using modern diagnostic imaging in order to preoperatively assess the
      degree of adhesion of the LN to adjacent structures.

PMID- 26209523
TI  - Weight cycling and cancer incidence in a large prospective US cohort.
AB  - Weight cycling, which consists of repeated cycles of intentional weight loss and
      regain, is common among individuals who try to lose weight. Some evidence
      suggests that weight cycling may affect biological processes that could
      contribute to carcinogenesis, but whether it is associated with cancer risk is
      unclear. Using 62,792 men and 69,520 women enrolled in the Cancer Prevention
      Study II Nutrition Cohort in 1992, we examined the association between weight
      cycling and cancer incidence. Weight cycles were defined by using baseline
      questions that asked the number of times >=10 pounds (4.54 kg) was purposely lost
      and later regained. Multivariable-adjusted hazard ratios and 95% confidence
      intervals for all cancer and 15 individual cancers were estimated by using Cox
      proportional hazards regression. During up to 17 years of follow-up, 15,333 men
      and 9,984 women developed cancer. Weight cycling was not associated with overall
      risk of cancer in men (hazard ratio = 0.96, 95% confidence interval: 0.83, 1.11
      for >=20 cycles vs. no weight cycles) or women (hazard ratio = 0.96, 95%
      confidence interval: 0.86, 1.08) in models that adjusted for body mass index and
      other covariates. Weight cycling was also not associated with any individual
      cancer investigated. These results suggest that weight cycling, independent of
      body weight, is unlikely to influence subsequent cancer risk. 

PMID- 26209524
TI  - Empirically Derived Trajectories to Dementia Over 15 Years of Follow-up
      Identified by Using Mixed Membership Models.
AB  - Alzheimer disease is the most common form of dementia in the elderly, and the
      complex relationships among risk factors produce highly variable natural
      histories from normal cognition through the prodromal stage of mild cognitive
      impairment (MCI) to clinical dementia. We used a novel statistical approach,
      mixed membership trajectory models, to capture the variety of such pathways in
      652 participants in the Cardiovascular Health Study Cognition Study over 22 years
      of follow-up (1992-2014). We identified 3 trajectories: a "healthy" profile with
      a peak probability of MCI between 95 and 100 years of age and only a 50%
      probability of dementia by age 100; an "intermediate" profile with a peak
      probability of MCI between 85 and 90 years of age and progression to dementia
      between 90 and 95 years; and an "unhealthy" profile with a peak probability of
      progressing to MCI between ages 75 and 80 years and to dementia between the ages
      of 80 and 85 years. Hypertension, education, race, and the epsilon4 allele of the
      apolipoprotein E gene all affected the closeness of an individual to 1 or more of
      the canonical trajectories. These results provide new insights into the natural
      history of Alzheimer disease and evidence for a potential difference in the
      pathophysiology of the development of dementia. 

PMID- 26209526
TI  - The Treatment of Juvenile Fibromyalgia with an Intensive Physical and
      Psychosocial Program.
AB  - OBJECTIVE: To assess the short-term and 1-year outcomes of children with
      fibromyalgia treated with intensive physical and occupational therapy (PT/OT) and
      psychotherapy. STUDY DESIGN: Children with fibromyalgia seen at a tertiary care
      hospital were treated with 5-6 hours of intensive PT/OT daily and at least 4
      hours of psychosocial services weekly. All medications used for fibromyalgia were
      discontinued. Children underwent standardized testing, including a visual analog
      scale for pain; the Bruininks-Oseretsky Test of Motor Performance, Second
      Edition; the Bruce treadmill protocol; the Functional Disability Inventory; the
      Pain Stages of Change Questionnaire, adolescent version; and the Pediatric
      Quality of Life Inventory, Teen Report, at 3 time points: at program entry, at
      the end of the intensive program, and 1 year after the end of the program.
      RESULTS: Sixty-four children (median age, 16 years; 95% Caucasian; 94% female;
      median duration of symptoms, 21 months) were studied. The mean pain score
      decreased significantly from program entry to the end of the program (from 66 of
      100 to 25 of 100; P = .001). At the 1-year follow-up, 33% reported no pain. All
      measures of function on the Bruininks-Oseretsky Test of Motor Performance, Second
      Edition improved significantly and remained at that level or continued to improve
      over the subsequent year. The mean Bruce treadmill protocol time first increased
      from 588 seconds to 801 seconds (P < .001) and then dropped to 750 seconds (P =
      .005), which is at the 90th percentile for age and sex. All Pain Stages of Change
      Questionnaire, adolescent version subset scores improved significantly initially
      and were stable or improved at 1 year, as did the Pediatric Quality of Life
      Inventory, Teen Report total score. CONCLUSION: Children with fibromyalgia can be
      successfully treated without medications with a very intensive PT/OT and
      psychotherapy program. They have significantly improved pain and function by
      subject report and objective measures of function.

PMID- 26209525
TI  - Controlled Ovarian Stimulation with recombinant-FSH plus recombinant-LH vs. human
      Menopausal Gonadotropin based on the number of retrieved oocytes: results from a
      routine clinical practice in a real-life population.
AB  - BACKGROUND: The association of recombinant FSH (rFSH) plus recombinant LH (rLH)
      is currently used for Controlled Ovarian Stimulation (COS) in human IVF, but its
      efficacy has, to date, not yet been compared to that of human Menopausal
      Gonadotropin (hMG), the FSH + LH activity-containing urinary drug. METHODS: Eight
      hundred forty-eight (848) IVF patients classified as expected "poor" or "normal"
      responders according to antral follicle count (AFC) and basal (day 3) FSH were
      treated with rFSH + rLH (2:1 ratio, n = 398, Group A) or hMG (n = 450, Group B).
      Data were collected under real-life practice circumstances and the pregnancy rate
      with fresh embryos was calculated by stratifying patients according to the number
      of retrieved oocytes (1-2, 3-4, 5-6, 7-8, >8). RESULTS: Overall, the pregnancy
      rate in both groups progressively improved according to the number of oocytes
      retrieved. When comparing patients within the same subgroup of oocyte yield,
      Group A and B showed a comparable outcome up to the reported highest yield (>8).
      When more than 8 oocytes were available, Group A had a significantly better
      pregnancy rate outcome. Patients' characteristics did not significantly differ
      between the two groups and the better outcome in the best responding patients in
      Group A was confirmed by a multivariable logistic regression analysis, that
      showed that both the use of rFSH + rLH and the total number of retrieved oocytes
      increased the probability of pregnancy with odd ratio (OR) of 1.628 and 1.083,
      respectively. CONCLUSIONS: When comparing patients with the same number of
      retrieved oocytes under real-life circumstances, the association of rFSH + rLH
      results in a significantly higher pregnancy rate than hMG when more than 8
      oocytes are retrieved. The reason(s) for this are unknown, but a more favorable
      effect on oocyte quality and/or endometrial receptivity could be involved.

PMID- 26209527
TI  - Menetrier Mimicker Complicating Ulcerative Colitis: Proton-Pump Inhibitor-Induced
      Hyperplastic Polyps.

PMID- 26209528
TI  - Breast cancer screening and diagnosis in the 21st century within the U.K.
AB  - In the UK, breast cancer represents the most commonly diagnosed cancer in females
      and carries with it a significant morbidity and mortality. An established
      national screening programme is in place to identify those with the disease at an
      early stage in order to optimise treatment and prognosis. This article provides
      an overview for the non-breast specialist clinician whose practice regularly
      deals with women who may be the subject of the screening programme. It outlines
      the diagnostic methods employed in the screening programme, the controversies
      that have surrounded it and the evolving technologies that will improve detection
      and diagnostic accuracy. 

PMID- 26209529
TI  - From Effort to Value: Preschool Children's Alternative to Effort Justification.
AB  - In the current studies, we addressed the development of effort-based object
      valuation. Four- and 6-year-olds invested either great or little effort in order
      to obtain attractive or unattractive rewards. Children were allowed to allocate
      these rewards to an unfamiliar recipient (dictator game). Investing great effort
      to obtain attractive rewards (a consonant situation) led 6-year-olds, but not 4
      year-olds, to enhance the value of the rewards and thus distribute fewer of them
      to others. After investing effort to attain unattractive rewards (a dissonant
      situation), 6-year-olds cognitively reduced the dissonance between effort and
      reward quality by reappraising the value of the rewards and thus distributing
      fewer of them. In contrast, 4-year-olds reduced the dissonance behaviorally by
      discarding the rewards. These findings provide evidence for the emergence of an
      effort-value link and underline possible mechanisms underlying the primacy of
      cognitive versus behavioral solutions to dissonance reduction. 

PMID- 26209530
TI  - Personality in Bonobos.
AB  - To better understand human and chimpanzee personality evolution, we obtained
      trait ratings of personality for 154 captive bonobos (~80% of the U.S. and
      European population). We found factors that we labeled Assertiveness,
      Conscientiousness, Openness, Agreeableness, Attentiveness, and Extraversion. The
      interrater reliabilities and test-retest reliabilities for these factors were
      comparable to those found in humans and other species. Using orthogonal targeted
      Procrustes rotations, we compared the bonobo dimensions with those of three
      samples of captive chimpanzees. Overall congruence coefficients indicated a fair
      degree of similarity; at the factor level, there was good evidence for
      Assertiveness, Conscientiousness, Openness, and Agreeableness in the chimpanzee
      samples; evidence for Attentiveness and Extraversion was poor. These findings
      suggest that, as expected given their close phylogenetic relationship, bonobo
      personality structure resembles chimpanzee personality structure in some
      respects. However, divergent evolution, perhaps as a result of socioecological
      differences between bonobos and chimpanzees, also appears to have shaped
      personality structure in these species.

PMID- 26209531
TI  - Can Faces Prime a Language?
AB  - Bilinguals have two languages that are activated in parallel. During speech
      production, one of these languages must be selected on the basis of some cue. The
      present study investigated whether the face of an interlocutor can serve as such
      a cue. Spanish-Catalan and Dutch-French bilinguals were first familiarized with
      certain faces, each of which was associated with only one language, during
      simulated Skype conversations. Afterward, these participants performed a language
      production task in which they generated words associated with the words produced
      by familiar and unfamiliar faces displayed on-screen. When responding to familiar
      faces, participants produced words faster if the faces were speaking the same
      language as in the previous Skype simulation than if the same faces were speaking
      a different language. Furthermore, this language priming effect disappeared when
      it became clear that the interlocutors were actually bilingual. These findings
      suggest that faces can prime a language, but their cuing effect disappears when
      it turns out that they are unreliable as language cues. 

PMID- 26209532
TI  - Cellular and molecular mechanisms of fungal beta-(1->6)-glucan in macrophages.
AB  - Over the last 40 yr, the majority of research on glucans has focused on beta-(1
      >3)-glucans. Recent studies indicate that beta-(1->6)-glucans may be even more
      potent immune modulators than beta-(1->3)-glucans. Mechanisms by which beta-(1
      >6)-glucans are recognized and modulate immunity are unknown. In this study, we
      examined the interaction of purified water-soluble beta-(1->6)-glucans with
      macrophage cell lines and primary peritoneal macrophages and the cellular and
      molecular consequences of this interaction. Our results indicate the existence of
      a specific beta-(1->6)-glucan receptor that internalizes the glucan ligand via a
      clathrin-dependent mechanism. We show that the known beta-(1->3)-glucans
      receptors are not responsible for beta-(1->6)-glucan recognition and interaction.
      The receptor-ligand uptake/interaction has an apparent dissociation constant (KD)
      of ~ 4 uM, and was associated with phosphorylation of ERK and JNK but not IkappaB
      alpha or p38. Our results indicate that macrophage interaction with beta-(1->6)
      glucans may lead to modulation of genes associated with anti-fungal immunity and
      recruitment/activation of neutrophils. In summary, we show that macrophages
      specifically bind and internalize beta-(1->6)-glucans followed by activation of
      intracellular signaling and modulation of anti-fungal immune response-related
      gene regulation. Thus, we conclude that the interaction between innate immunity
      and beta-(1->6)-glucans may play an important role in shaping the anti-fungal
      immune response.

PMID- 26209533
TI  - Zebrafish adult-derived hypothalamic neurospheres generate gonadotropin-releasing
      hormone (GnRH) neurons.
AB  - Gonadotropin-releasing hormone (GnRH) is a hypothalamic decapeptide essential for
      fertility in vertebrates. Human male patients lacking GnRH and treated with
      hormone therapy can remain fertile after cessation of treatment suggesting that
      new GnRH neurons can be generated during adult life. We used zebrafish to
      investigate the neurogenic potential of the adult hypothalamus. Previously we
      have characterized the development of GnRH cells in the zebrafish linking genetic
      pathways to the differentiation of neuromodulatory and endocrine GnRH cells in
      specific regions of the brain. Here, we developed a new method to obtain neural
      progenitors from the adult hypothalamus in vitro. Using this system, we show that
      neurospheres derived from the adult hypothalamus can be maintained in culture and
      subsequently differentiate glia and neurons. Importantly, the adult derived
      progenitors differentiate into neurons containing GnRH and the number of cells is
      increased through exposure to either testosterone or GnRH, hormones used in
      therapeutic treatment in humans. Finally, we show in vivo that a neurogenic niche
      in the hypothalamus contains GnRH positive neurons. Thus, we demonstrated for the
      first time that neurospheres can be derived from the hypothalamus of the adult
      zebrafish and that these neural progenitors are capable of producing GnRH
      containing neurons. 

PMID- 26209534
TI  - VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation
      and proliferation in skin cancer cells.
AB  - Neuropilin-1 (NRP1) has been identified as a VEGF-A receptor. DJM-1, a human skin
      cancer cell line, expresses endogenous VEGF-A and NRP1. In the present study, the
      RNA interference of VEGF-A or NRP1 suppressed DJM-1 cell proliferation.
      Furthermore, the overexpression of the NRP1 wild type restored shNRP1-treated DJM
      1 cell proliferation, whereas NRP1 cytoplasmic deletion mutants did not. A co
      immunoprecipitation analysis revealed that VEGF-A induced interactions between
      NRP1 and GIPC1, a scaffold protein, and complex formation between GIPC1 and Syx,
      a RhoGEF. The knockdown of GIPC1 or Syx reduced active RhoA and DJM-1 cell
      proliferation without affecting the MAPK or Akt pathway. C3 exoenzyme or Y27632
      inhibited the VEGF-A-induced proliferation of DJM-1 cells. Conversely, the
      overexpression of the constitutively active form of RhoA restored the
      proliferation of siVEGF-A-treated DJM-1 cells. Furthermore, the inhibition of
      VEGF-A/NRP1 signaling upregulated p27, a CDK inhibitor. A cell-penetrating
      oligopeptide that targeted GIPC1/Syx complex formation inhibited the VEGF-A
      induced activation of RhoA and suppressed DJM-1 cell proliferation. In
      conclusion, this new signaling pathway of VEGF-A/NRP1 induced cancer cell
      proliferation by forming a GIPC1/Syx complex that activated RhoA to degrade the
      p27 protein. 

PMID- 26209535
TI  - Daily low-dose hCG stimulation during the luteal phase combined with GnRHa
      triggered IVF cycles without exogenous progesterone: a proof of concept trial.
AB  - STUDY QUESTION: Can the luteal phase support be improved in terms of efficacy,
      hormonal profiles and convenience as compared with today's standard care? SUMMARY
      ANSWER: Daily low-dose rhCG supplementation in GnRHa triggered IVF cycles can
      replace the traditional used luteal phase support with exogenous progesterone.
      WHAT IS KNOWN ALREADY: A bolus of hCG for final maturation of follicles in
      connection with COS may induce the risk of OHSS and the luteal phase progesterone
      levels rise very abruptly in the early luteal phase. STUDY DESIGN, SIZE,
      DURATION: This is a proof-of-concept study conducted as a three arm RCT with a
      total of 93 patients. First patient enrolled in January 2012 and the study
      finished in January 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Normal
      responder women undergoing IVF/ICSI treatment in a university hospital. One arm
      served as control, where women followed a standard antagonist protocol. Two study
      arms were included both having 125 IU hCG daily for luteal phase support without
      exogenous progesterone after using a GnRHa trigger for ovulation induction. In
      both study arms exogenous FSH was stopped on stimulation day 6 and replaced by
      exogenous hCG that was initiated on either stimulation day 2 or day 6. Blood
      samples were obtained on the day of ovulation induction, on the day of oocyte
      pickup (OPU) and day OPU + 7. MAIN RESULTS AND THE ROLE OF CHANCE: The mean serum
      levels of hCG did not exceeded the normal physiological range of LH activity in
      any samples. Mid-luteal progesterone levels were significantly higher in the two
      study groups receiving daily low-dose hCG for luteal phase support as compared
      with the control group (control group: 177 +/- 27 nmol/l; study group 1: 334 +/-
      42 nmol/l; study group 2: 277 +/- 27 nmol/l; (mean +/- SEM). No differences in
      reproductive outcome were seen between groups. LIMITATIONS, REASONS FOR CAUTION:
      The number of patients included is limited and conclusions need to be verified in
      a larger RCT. WIDER IMPLICATIONS OF THE FINDINGS: Endogenous production of
      progesterone may become more attractive as the luteal phase support with levels
      of LH-like activity only in the physiological range and may, from the patients'
      point of view, replace inconvenient exogenous progesterone preparation. Further
      hCG may reduce the cost of stimulation and may collectively be used for
      stimulation of the follicular phase, ovulation induction and for luteal phase
      support. STUDY FUNDING/COMPETING INTERESTS: An unrestricted grant from ARTS
      Biologics made this study possible. None of the authors has any competing
      interests to declare. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov number:
      NCT01504139. TRIAL REGISTRATION DATE: 28 December 2011.

PMID- 26209536
TI  - Clarification of scope for Human Reproduction and Molecular Human Reproduction.

PMID- 26209537
TI  - Rat cytomegalovirus (RCMV) English isolate and a newly identified Berlin isolate
      share similarities with but are separate as an anciently diverged clade from
      Mouse CMV and the Maastricht isolate of RCMV.
AB  - The genome of the rat cytomegalovirus (RCMV) English isolate (MuHV-8) differs
      significantly from the RCMV Maastricht isolate (MuHV-2) and other
      cytomegaloviruses (CMVs) in its size, base composition and genomic content.
      Analysis of the RCMV-Berlin isolate, MuHV-8, revealed that the two MuHV-8
      isolates are highly similar in genome size and content, indicating that the
      smaller genome size (202 946 bp) compared to other known CMVs was not the result
      of an accidental deletion during passage in tissue culture. Surprisingly, the
      proteins encoded in MuHV-8 shared more overall similarity with their orthologues
      from mouse CMV (MuHV-1) compared to their orthologues in rat CMV (MuHV-2).
      Phylogenetic analyses of conserved viral genes showed that the two MuHV-8
      isolates are from the same species and represent a unique clade that is distinct
      from other rodent CMVs. 

PMID- 26209538
TI  - New Compound Targets Warburg Effect.

PMID- 26209539
TI  - Pancreatic Cancer Metastases Harbor Evidence of Polyclonality.
AB  - Studies of the cancer genome have demonstrated that tumors are composed of
      multiple subclones with varied genetic and phenotypic properties. However, little
      is known about how metastases arise and evolve from these subclones. To
      understand the cellular dynamics that drive metastasis, we used multicolor
      lineage-tracing technology in an autochthonous mouse model of pancreatic cancer.
      Here, we report that precursor lesions exhibit significant clonal heterogeneity
      but that this diversity decreases during premalignant progression. Furthermore,
      we present evidence that a significant fraction of metastases are polyclonally
      seeded by distinct tumor subclones. Finally, we show that clonality during
      metastatic growth-leading to either monoclonal or polyclonal expansion-differs
      based on the site of metastatic invasion. These results provide an unprecedented
      window into the cellular dynamics of tumor evolution and suggest that heterotypic
      interactions between tumor subpopulations contribute to metastatic progression in
      native tumors. SIGNIFICANCE: Studies of tumor heterogeneity indicate that
      distinct tumor subclones interact during cancer progression. Here, we demonstrate
      by lineage tracing that metastases often involve seeding by more than one clone
      and that subsequent cellular outgrowth depends on the metastatic site. These
      findings provide insight into clonal diversity and evolution in metastatic
      disease.

PMID- 26209540
TI  - Radiotherapy for the prophylaxis of heterotopic ossification: A single 7-8Gy
      fraction seems optimal.

PMID- 26209541
TI  - Plasma Iohexol Clearance for Assessing Residual Kidney Function in Dialysis
      Patients.

PMID- 26209542
TI  - Aerobic or Resistance Training and Pulse Wave Velocity in Kidney Transplant
      Recipients: A 12-Week Pilot Randomized Controlled Trial (the Exercise in Renal
      Transplant [ExeRT] Trial).
AB  - BACKGROUND: Cardiovascular disease remains the leading cause of death in kidney
      transplant recipients. This pilot study examined the potential effect of aerobic
      training or resistance training on vascular health and indexes of cardiovascular
      risk in kidney transplant recipients. STUDY DESIGN: Single-blind, randomized,
      controlled, parallel trial. SETTING & PARTICIPANTS: 60 participants (mean age, 54
      years; 34 men) were randomly assigned to aerobic training (n=20), resistance
      training (n=20), or usual care (n=20). Participants were included if they had a
      kidney transplant within 12 months prior to baseline assessment. Patients were
      excluded if they had unstable medical conditions or had recently started regular
      exercise. INTERVENTION: Aerobic training and resistance training were delivered 3
      days per week for a 12-week period. The usual-care group received standard care.
      OUTCOMES & MEASUREMENTS: Pulse wave velocity, peak oxygen uptake (Vo2peak), sit
      to-stand 60, isometric quadriceps force, and inflammatory biomarkers were
      assessed at 0 and 12 weeks. RESULTS: The anticipated 60 participants were
      recruited within 12 months. 46 participants completed the study (aerobic
      training, n=13; resistance training, n=13; and usual care, n=20), resulting in a
      23% attrition rate. Analyses of covariance, adjusted for baseline values, age,
      and dialysis vintage pretransplantation, revealed significant mean differences
      between aerobic training and usual care in pulse wave velocity of -2.2+/-0.4 (95%
      CI, -3.1 to -1.3) m/s (P<0.001) and between resistance training and usual care of
      -2.6+/-0.4 (95% CI, -3.4 to -1.7) m/s (P<0.001) at 12 weeks. Secondary analyses
      indicated significant improvements in Vo2peak in the aerobic training group and
      in Vo2peak, sit-to-stand 60, and isometric muscle force in the resistance
      training group compared with usual care at 12 weeks. There were no reported
      adverse events, cardiovascular events, or hospitalizations as a result of the
      intervention. LIMITATIONS: Pilot study, small sample size, no measure of
      endothelial function. CONCLUSIONS: Both aerobic training and resistance training
      interventions appear to be feasible and clinically beneficial in this patient
      population.

PMID- 26209543
TI  - Randomized controlled trial of mycophenolate mofetil in children, adolescents,
      and adults with IgA nephropathy.
AB  - BACKGROUND: Previous randomized controlled trials evaluating the efficacy of
      mycophenolate mofetil (MMF) in patients with immunoglobulin A nephropathy (IgAN)
      have produced varying results. STUDY DESIGN: Double-blind placebo-controlled
      randomized controlled trial. SETTING & PARTICIPANTS: 52 children, adolescents,
      and adults with biopsy-proven IgAN in 30 centers in the United States and Canada.
      Entry criteria: age older than 7 to younger than 70 years; urine protein
      creatinine ratio (UPCR), >=0.6g/g (males) or >=0.8g/g (females); and estimated
      glomerular filtration rate >= 50mL/min/1.73m(2) (>=40mL/min/1.73m(2) if receiving
      angiotensin-converting enzyme inhibitor). Mean age, 32+/-12 (SD) years; 62% men;
      and 73% white. INTERVENTION: Lisinopril (or losartan) plus a highly purified
      omega-3 fatty acid (Omacor [Pronova Biocare]) was given to 94 patients for 3
      months; 52 of the patients with persistent UPCR>=0.6g/g (males) and >=0.8g/g
      (females) were randomly assigned to MMF or placebo (target dose, 25-36mg/kg/d) in
      addition to lisinopril/losartan plus Omacor. OUTCOMES: Change in UPCR after 6 and
      12 months treatment with MMF/placebo and 12 months after the end of treatment.
      MEASUREMENTS: UPCR measured on 24-hour urine samples. Glomerular filtration rate
      estimated with the Schwartz (age < 18 years) or Cockcroft-Gault (age >= 18 years)
      formula. RESULTS: 44 patients completed 6 months of treatment with MMF (n=22) or
      placebo (n=22). The trial was terminated early at the recommendation of the Data
      Monitoring Committee because of the lack of benefit. No patient achieved a
      complete remission (UPCR<0.2g/g). Mean UPCRs at randomization and after 6 months
      were 1.45 (95% CI, 1.16-1.75) and 1.40 (95% CI, 1.09-1.70) for MMF and 1.41 (95%
      CI, 1.17-1.65) and 1.58 (95% CI, 1.13-2.04) for placebo, respectively. The mean
      difference in UPCR change between these groups (MMF minus placebo) was -0.22 (95%
      CI, -0.75 to 0.31; P=0.4). Adverse events were rare apart from nausea (MMF, 8.7%;
      placebo, 3.7%); one of these MMF patients withdrew. LIMITATIONS: Low patient
      enrollment and short follow-up. CONCLUSIONS: MMF did not reduce proteinuria
      significantly in patients with IgAN who had persistent proteinuria after
      lisinopril/losartan plus Omacor.

PMID- 26209545
TI  - Long-Lasting Metabolic Imbalance Related to Obesity Alters Olfactory Tissue
      Homeostasis and Impairs Olfactory-Driven Behaviors.
AB  - Obesity is associated with chronic food intake disorders and binge eating. Food
      intake relies on the interaction between homeostatic regulation and hedonic
      signals among which, olfaction is a major sensory determinant. However, its
      potential modulation at the peripheral level by a chronic energy imbalance
      associated to obese status remains a matter of debate. We further investigated
      the olfactory function in a rodent model relevant to the situation encountered in
      obese humans, where genetic susceptibility is juxtaposed on chronic eating
      disorders. Using several olfactory-driven tests, we compared the behaviors of
      obesity-prone Sprague-Dawley rats (OP) fed with a high-fat/high-sugar diet with
      those of obese-resistant ones fed with normal chow. In OP rats, we reported 1)
      decreased odor threshold, but 2) poor olfactory performances, associated with
      learning/memory deficits, 3) decreased influence of fasting, and 4) impaired
      insulin control on food seeking behavior. Associated with these behavioral
      modifications, we found a modulation of metabolism-related factors implicated in
      1) electrical olfactory signal regulation (insulin receptor), 2) cellular
      dynamics (glucorticoids receptors, pro- and antiapoptotic factors), and 3)
      homeostasis of the olfactory mucosa and bulb (monocarboxylate and glucose
      transporters). Such impairments might participate to the perturbed daily food
      intake pattern that we observed in obese animals. 

PMID- 26209544
TI  - Hyperuricemia and Progression of CKD in Children and Adolescents: The Chronic
      Kidney Disease in Children (CKiD) Cohort Study.
AB  - BACKGROUND: Hyperuricemia is associated with essential hypertension in children.
      No previous studies have evaluated the effect of hyperuricemia on progression of
      chronic kidney disease (CKD) in children. STUDY DESIGN: Prospective observational
      cohort study. SETTING & PARTICIPANTS: Children and adolescents (n=678 cross
      sectional; n=627 longitudinal) with a median age of 12.3 (IQR, 8.6-15.6) years
      enrolled at 52 North American sites of the CKiD (CKD in Children) Study.
      PREDICTOR: Serum uric acid level (<5.5, 5.5-7.5, and >7.5mg/dL). OUTCOMES:
      Composite end point of either >30% decline in glomerular filtration rate (GFR) or
      initiation of renal replacement therapy. MEASUREMENTS: Age, sex, race, blood
      pressure status, GFR, CKD cause, urine protein-creatinine ratio (<0.5, 0.5-<2.0,
      and >=2.0mg/mg), age- and sex-specific body mass index > 95th percentile, use of
      diuretics, and serum uric acid level. RESULTS: Older age, male sex, lower GFR,
      and body mass index > 95th percentile were associated with higher uric acid
      levels. 162, 294, and 171 participants had initial uric acid levels < 5.5, 5.5 to
      7.5, or >7.5 mg/dL, respectively. We observed 225 instances of the composite end
      point over 5 years. In a multivariable parametric time-to-event analysis,
      compared with participants with initial uric acid levels < 5.5mg/dL, those with
      uric acid levels of 5.5 to 7.5 or >7.5mg/dL had 17% shorter (relative time, 0.83;
      95% CI, 0.62-1.11) or 38% shorter (relative time, 0.62; 95% CI, 0.45-0.85) times
      to event, respectively. Hypertension, lower GFR, glomerular CKD cause, and
      elevated urine protein-creatinine ratio were also associated with faster times to
      the composite end point. LIMITATIONS: The study lacked sufficient data to examine
      how use of specific medications might influence serum uric acid levels and CKD
      progression. CONCLUSIONS: Hyperuricemia is a previously undescribed independent
      risk factor for faster progression of CKD in children and adolescents. It is
      possible that treatment of children and adolescents with CKD with urate-lowering
      therapy could slow disease progression.

PMID- 26209546
TI  - Effort-Based Decision-Making Paradigms for Clinical Trials in Schizophrenia: Part
      2-External Validity and Correlates.
AB  - Effort-based decision making has strong conceptual links to the motivational
      disturbances that define a key subdomain of negative symptoms. However, the
      extent to which effort-based decision-making performance relates to negative
      symptoms, and other clinical and functionally important variables has yet to be
      systematically investigated. In 94 clinically stable outpatients with
      schizophrenia, we examined the external validity of 5 effort-based paradigms,
      including the Effort Expenditure for Rewards, Balloon Effort, Grip Strength
      Effort, Deck Choice Effort, and Perceptual Effort tasks. These tasks covered 3
      types of effort: physical, cognitive, and perceptual. Correlations between effort
      related performance and 6 classes of variables were examined, including: (1)
      negative symptoms, (2) clinically rated motivation and community role
      functioning, (3) self-reported motivational traits, (4) neurocognition, (5) other
      psychiatric symptoms and clinical/demographic characteristics, and (6) subjective
      valuation of monetary rewards. Effort paradigms showed small to medium
      relationships to clinical ratings of negative symptoms, motivation, and
      functioning, with the pattern more consistent for some measures than others. They
      also showed small to medium relations with neurocognitive functioning, but were
      generally unrelated to other psychiatric symptoms, self-reported traits,
      antipsychotic medications, side effects, and subjective valuation of money. There
      were relatively strong interrelationships among the effort measures. In
      conjunction with findings from a companion psychometric article, all the
      paradigms warrant further consideration and development, and 2 show the strongest
      potential for clinical trial use at this juncture. 

PMID- 26209547
TI  - Treatments for Delusional Disorder.

PMID- 26209549
TI  - Clarification of scope for Human Reproduction and Molecular Human Reproduction?.

PMID- 26209548
TI  - A Meta-Analysis of Autobiographical Memory Studies in Schizophrenia Spectrum
      Disorder.
AB  - Meta-analyses and reviews on cognitive disorders in schizophrenia have shown that
      the most robust and common cognitive deficits are found in episodic memory and
      executive functions. More complex memory domains, such as autobiographical memory
      (AM), are also impaired in schizophrenia, but such impairments are reported less
      often despite their negative impact on patients' outcome. In contrast to episodic
      memory, assessed in laboratory tasks, memories of past personal events are much
      more complex and directly relate to the self. The meta-analysis included 20
      studies, 571 patients with schizophrenia spectrum disorder, and 503 comparison
      subjects. It found moderate-to-large effect sizes with regard to the 3 parameters
      commonly used to assess AM: memory specificity (g = -0.97), richness of detail (g
      = -1.40), and conscious recollection (g = -0.62). These effect sizes were in the
      same range as those found in other memory domains in schizophrenia; for this
      reason, we propose that defective memories of personal past events should be
      regarded as a major cognitive impairment in this illness. 

PMID- 26209550
TI  - Comparison of hard tissues that are useful for DNA analysis in forensic autopsy.
AB  - Forensic analysis of DNA from hard tissues can be important when investigating a
      variety of cases resulting from mass disaster or criminal cases. This study was
      conducted to evaluate the most suitable tissues, method and sample size for
      processing of hard tissues prior to DNA isolation. We also evaluated the elapsed
      time after death in relation to the quantity of DNA extracted. Samples of hard
      tissues (37 teeth, 42 skull, 42 rib, and 39 nails) from 42 individuals aged
      between 50 and 83 years were used. The samples were taken from remains following
      forensic autopsy (from 2 days to 2 years after death). To evaluate the integrity
      of the nuclear DNA isolated, the percentage of allele calls for short tandem
      repeat profiles were compared between the hard tissues. DNA typing results
      indicated that until 1 month after death, any of the four hard tissue samples
      could be used as an alternative to teeth, allowing analysis of all of the loci.
      However, in terms of the sampling site, collection method and sample size
      adjustment, the rib appeared to be the best choice in view of the ease of
      specimen preparation. Our data suggest that the rib could be an alternative hard
      tissue sample for DNA analysis of human remains.

PMID- 26209552
TI  - Persistence of endoscopic rectal inflammation in UC treated with infliximab is
      not linked to ineffective TNFalpha downregulation.

PMID- 26209551
TI  - Pathogenesis of myeloproliferative neoplasms.
AB  - Major progress has been recently made in understanding the molecular pathogenesis
      of myeloproliferative neoplasms (MPN). Mutations in one of four genes-JAK2, MPL,
      CALR, and CSF3R-can be found in the vast majority of patients with MPN and
      represent driver mutations that can induce the MPN phenotype. Hyperactive
      JAK/STAT signaling appears to be the common denominator of MPN, even in patients
      with CALR mutations and the so-called "triple-negative" MPN, where the driver
      gene mutation is still unknown. Mutations in epigenetic regulators, transcription
      factors, and signaling components modify the course of the disease and can
      contribute to disease initiation and/or progression. The central role of JAK2 in
      MPN allowed development of small molecular inhibitors that are in clinical use
      and are active in almost all patients with MPN. Advances in understanding the
      mechanism of JAK2 activation open new perspectives of developing the next
      generation of inhibitors that will be selective for the mutated forms of JAK2. 

PMID- 26209553
TI  - Differential effects of alpha4beta7 and GPR15 on homing of effector and
      regulatory T cells from patients with UC to the inflamed gut in vivo.
AB  - OBJECTIVE: Gut homing of lymphocytes via adhesion molecules has recently emerged
      as new target for therapy in IBDs. We aimed to analyse the in vivo homing of
      effector (Teff) and regulatory (Treg) T cells to the inflamed gut via alpha4beta7
      and G protein receptor GPR15. DESIGN: We assessed the expression of homing
      receptors on T cells in peripheral blood and inflamed mucosa. We studied the
      migration pattern and homing of Teff and Treg cells to the inflamed gut using
      intravital confocal microscopy and FACS in a humanised mouse model in dextran
      sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. RESULTS:
      Expression of GPR15 and alpha4beta7 was significantly increased on Treg rather
      than Teff cells in peripheral blood of patients with UC as compared with Crohn's
      disease and controls. In vivo analysis in a humanised mouse model showed
      augmented gut homing of UC Treg cells as compared with controls. Moreover,
      suppression of UC (but not control) Teff and Treg cell homing was noted upon
      treatment with the alpha4beta7 antibody vedolizumab. In contrast, siRNA blockade
      of GPR15 had only effects on homing of Teff cells but did not affect Treg homing
      in UC. Clinical vedolizumab treatment was associated with marked expansion of UC
      Treg cells in peripheral blood. CONCLUSIONS: alpha4beta7 rather than GPR15 is
      crucial for increased colonic homing of UC Treg cells in vivo, while both
      receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC
      Treg cells leading to their accumulation in peripheral blood with subsequent
      suppression of systemic Teff cell expansion.

PMID- 26209554
TI  - Novel DICER-LIKE1 siRNAs Bypass the Requirement for DICER-LIKE4 in Maize
      Development.
AB  - Dicer enzymes function at the core of RNA silencing to defend against exogenous
      RNA or to regulate endogenous genes. Plant DICER-LIKE4 (DCL4) performs dual
      functions, acting in antiviral defense and in development via the biogenesis of
      trans-acting short-interfering RNAs (siRNAs) termed tasiR-ARFs. These small RNAs
      play an essential role in the grasses, spatially defining the expression domain
      of AUXIN RESPONSE FACTOR3 (ARF3) transcription factors. However, contrary to
      tasiR-ARFs' essential function in development, DCL4 proteins exhibit strong
      evidence of recurrent adaptation typical of host factors involved in antiviral
      immunity. Here, we address how DCL4 balances its role in development with
      pressures to diversify in response to viral attack. We show that, in contrast to
      other tasiR-ARF biogenesis mutants, dcl4 null alleles have an
      uncharacteristically mild phenotype, correlated with normal expression of select
      arf3 targets. Loss of DCL4 activity yields a class of 22-nucleotide tasiR-ARF
      variants associated with the processing of arf3 transcripts into 22-nucleotide
      secondary siRNAs by DCL1. Our findings reveal a DCL1-dependent siRNA pathway that
      bypasses the otherwise adverse developmental effects of mutations in DCL4. This
      pathway is predicted to have important implications for DCL4's role in antiviral
      defense by reducing the selective constraints on DCL4 and allowing it to
      diversify in response to viral suppressors. 

PMID- 26209555
TI  - Comprehensive Annotation of Physcomitrella patens Small RNA Loci Reveals That the
      Heterochromatic Short Interfering RNA Pathway Is Largely Conserved in Land
      Plants.
AB  - Many plant small RNAs are sequence-specific negative regulators of target mRNAs
      and/or chromatin. In angiosperms, the two most abundant endogenous small RNA
      populations are usually 21-nucleotide microRNAs (miRNAs) and 24-nucleotide
      heterochromatic short interfering RNAs (siRNAs). Heterochromatic siRNAs are
      derived from repetitive regions and reinforce DNA methylation at targeted loci.
      The existence and extent of heterochromatic siRNAs in other land plant lineages
      has been unclear. Using small RNA-sequencing (RNA-seq) of the moss Physcomitrella
      patens, we identified 1090 loci that produce mostly 23- to 24-nucleotide siRNAs.
      These loci are mostly in intergenic regions with dense DNA methylation.
      Accumulation of siRNAs from these loci depends upon P. patens homologs of DICER
      LIKE3 (DCL3), RNA-DEPENDENT RNA POLYMERASE2, and the largest subunit of DNA
      DEPENDENT RNA POLYMERASE IV, with the largest subunit of a Pol V homolog
      contributing to expression at a smaller subset of the loci. A MINIMAL DICER-LIKE
      (mDCL) gene, which lacks the N-terminal helicase domain typical of DCL proteins,
      is specifically required for 23-nucleotide siRNA accumulation. We conclude that
      heterochromatic siRNAs, and their biogenesis pathways, are largely identical
      between angiosperms and P. patens, with the notable exception of the P. patens
      specific use of mDCL to produce 23-nucleotide siRNAs. 

PMID- 26209556
TI  - Expression and characterization of the gD protein of HSV-2 fused to the
      tetramerization domain of the transcription factor p53.
AB  - The highly immunogenic glycoprotein D (gD) of herpes simplex virus type 2 (HSV-2)
      is a very important element for entry of this virus into host cells. These
      characteristics have made this protein a very interesting HSV-2 subunit vaccine
      candidate. Despite efforts to prevent genital herpes using gD-based subunit
      vaccines, to date, clinical trials using this antigen have failed. Therefore,
      using a small animal model, we sought to determine if a tetramerized truncated
      form of gD subunit vaccine, produced by recombinant baculovirus infected insect
      larvae, would elicit better protection against genital herpes than a monomeric gD
      2 subunit vaccine. Three out of 5 mice immunized with the tetramerized antigen
      produced in a baculovirus expression vector system, survived a lethal challenge
      with a wild type HSV-2 strain (for more than 3 weeks after challenge). In
      contrast, all the mice (5) immunized with the truncated protein, produced by the
      same methodology, died within 2 weeks after challenge. These results suggest that
      multimerization (increasing the structural complexity) of the truncated gD
      antigen might be more likely protective than the monomer form. Also the use of an
      alternative cost-efficient eukaryotic expression system is described.

PMID- 26209559
TI  - Endogenous 2-Arachidonoylglycerol Alleviates Cyclooxygenases-2 Elevation-Mediated
      Neuronal Injury From SO2 Inhalation via PPARgamma Pathway.
AB  - Although the health effects of sulfur dioxide (SO2) pollution in the atmospheric
      environment are not new, epidemiological studies and parallel experimental
      investigations indicate that acute SO2 exposure causes glutamate-mediated
      excitotoxicity and even contributes to the outcome of cerebral ischemia.
      Additionally, the free radical-related inflammatory responses are responsible for
      neuronal insults and consequent brain disorders. However, few medications are
      available for preventing the inflammatory responses and relieving the subsequent
      harmful insults from SO2 inhalation. Here, we show that endocannabinoid 2
      arachidonoylglycerol (2-AG) prevents neurotoxicity from SO2 inhalation by
      suppressing cyclooxygenase-2 (COX-2) overexpression, and this action appears to
      be mediated via cannabinoid receptor 1 (CB1)-dependent mitogen-activated protein
      kinase/nuclear factor kappaB (NF-kappaB) signaling pathways. Furthermore, CB1
      dependent peroxisome proliferator activated receptor gamma (PPARgamma) expression
      was an important modulator of the 2-AG-mediated resolution on NF-kappaB-coupled
      COX-2 elevation in response to SO2 neuroinflammation. This finding provides
      evidence of a possible therapeutic effect of endogenous 2-AG regulation for
      protecting against neurological dysfunction from SO2 inhalation in polluted
      areas. 

PMID- 26209557
TI  - Linkage Analysis of Urine Arsenic Species Patterns in the Strong Heart Family
      Study.
AB  - Arsenic toxicokinetics are important for disease risks in exposed populations,
      but genetic determinants are not fully understood. We examined urine arsenic
      species patterns measured by HPLC-ICPMS among 2189 Strong Heart Study
      participants 18 years of age and older with data on ~400 genome-wide
      microsatellite markers spaced ~10 cM and arsenic speciation (683 participants
      from Arizona, 684 from Oklahoma, and 822 from North and South Dakota). We logit
      transformed % arsenic species (% inorganic arsenic, %MMA, and %DMA) and also
      conducted principal component analyses of the logit % arsenic species. We used
      inverse-normalized residuals from multivariable-adjusted polygenic heritability
      analysis for multipoint variance components linkage analysis. We also examined
      the contribution of polymorphisms in the arsenic metabolism gene AS3MT via
      conditional linkage analysis. We localized a quantitative trait locus (QTL) on
      chromosome 10 (LOD 4.12 for %MMA, 4.65 for %DMA, and 4.84 for the first principal
      component of logit % arsenic species). This peak was partially but not fully
      explained by measured AS3MT variants. We also localized a QTL for the second
      principal component of logit % arsenic species on chromosome 5 (LOD 4.21) that
      was not evident from considering % arsenic species individually. Some other loci
      were suggestive or significant for 1 geographical area but not overall across all
      areas, indicating possible locus heterogeneity. This genome-wide linkage scan
      suggests genetic determinants of arsenic toxicokinetics to be identified by
      future fine-mapping, and illustrates the utility of principal component analysis
      as a novel approach that considers % arsenic species jointly.

PMID- 26209558
TI  - Impact of Low-Dose Oral Exposure to Bisphenol A (BPA) on Juvenile and Adult Rat
      Exploratory and Anxiety Behavior: A CLARITY-BPA Consortium Study.
AB  - Bisphenol A (BPA) is a high volume production chemical and has been identified as
      an endocrine disruptor, prompting concern that developmental exposure could
      impact brain development and behavior. Rodent and human studies suggest that
      early life BPA exposure may result in an anxious, hyperactive phenotype but
      results are conflicting and data from studies using multiple doses below the no
      observed-adverse-effect level are limited. To address this, the present studies
      were conducted as part of the CLARITY-BPA (Consortium Linking Academic and
      Regulatory Insights on BPA Toxicity) program. The impact of perinatal BPA
      exposure (2.5, 25, or 2500 ug/kg body weight (bw)/day) on behaviors related to
      anxiety and exploratory activity was assessed in juvenile (prepubertal) and adult
      NCTR Sprague-Dawley rats of both sexes. Ethinyl estradiol (0.5 ug/kg bw/day) was
      used as a reference estrogen. Exposure spanned gestation and lactation with dams
      gavaged from gestational day 6 until birth and then the offspring gavaged
      directly through weaning (n = 12/sex/group). Behavioral assessments included open
      field, elevated plus maze, and zero maze. Anticipated sex differences in behavior
      were statistically identified or suggested in most cases. No consistent effects
      of BPA were observed for any endpoint, in either sex, at either age compared to
      vehicle controls; however, significant differences between BPA-exposed and
      ethinyl estradiol-exposed groups were identified for some endpoints. Limitations
      of this study are discussed and include suboptimal statistical power and low
      concordance across behavioral tasks. These data do not indicate BPA-related
      effects on anxiety or exploratory activity in these developmentally exposed rats.

PMID- 26209560
TI  - Antimicrobial peptide protonectin disturbs the membrane integrity and induces ROS
      production in yeast cells.
AB  - Candidiasis is often observed in immunocompromised patients and is the 4th most
      common cause of bloodstream infections. However, antifungals are limited, so
      novel antifungal agents are urgently needed. Antimicrobial peptides (AMPs) are
      considered as potential alternatives of conventional antibiotics. In the present
      study, antimicrobial peptide protonectin was chemically synthesized and its
      antifungal activity and mode of action were studied. Our results showed that
      protonectin has potent antifungal activity and fungicidal activity against the
      tested fungi cells. Its action mode involved the disruption of the membrane
      integrity and the inducing of the production of cellular ROS. Furthermore,
      protonectin could inhibit the formation of biofilm and kill the adherent fungi
      cells. In conclusion, with the increase of fungal infection, protonectin may
      offer a new strategy and be considered as a potential therapeutic agent against
      fungal disease. 

PMID- 26209561
TI  - Editorial overview: molecular biology of sensation.

PMID- 26209562
TI  - Hand Therapy Modalities Following Extensor Mechanism Surgery.

PMID- 26209563
TI  - Robust inhibitory effects of conjugated linolenic acids on a cyclooxygenase
      related linoleate 10S-dioxygenase: Comparison with COX-1 and COX-2.
AB  - There are many reports of the anti-inflammatory, anti-cancer, and anti
      atherosclerotic activities of conjugated linolenic acids (cLNA). They constitute
      a small percentage of fatty acids in the typical human diet, although up to 80%
      of the fatty acids in certain fruits such as pomegranate. In the course of
      studying a bacterial fatty acid dioxygenase (Nostoc linoleate 10S-DOX, an ancient
      relative of mammalian cyclooxygenases), we detected strong inhibitory activity in
      a commercial sample of linoleic acid. We identified two cLNA isomers, beta
      eleostearic (9E,11E,13E-18:3) and beta-calendic acid (8E,10E,12E-18:3), as
      responsible for that striking inhibition with a Ki of ~49nM and ~125nM,
      respectively, the most potent among eight cLNA tested. We also examined the
      effects of all eight cLNA on the activity of COX-1 and COX-2. Jacaric acid
      (8Z,10E,12Z-18:3) and its 12E isomer, 8Z,10E,12E-18:3, strongly inhibit the
      activity of COX-1 with a Ki of ~1.7 and ~1.1MUM, respectively. By contrast, COX-2
      was <=30% inhibited at 10MUM concentrations of the cLNA. Identifying the
      activities of the naturally occurring fatty acids is of interest in terms of
      understanding their interaction with the enzymes, and for explaining the
      mechanistic basis of their biological effects. The study also highlights the
      potential presence of inhibitory fatty acids in commercial lipids prepared from
      natural sources. Analysis of seven commercial samples of linoleic acid by HPLC
      and UV spectroscopy is illustrated as supplementary data. 

PMID- 26209566
TI  - Intraoperative near-infrared fluorescence visualization of the duodenal
      gastrinoma in a patient with Zollinger-Ellison syndrome.

PMID- 26209567
TI  - Prediction of posthepatectomy liver failure based on liver stiffness measurement
      in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Posthepatectomy liver failure (PHLF) is a potentially fatal
      complication, and the accurate prediction of PHLF is essential. Liver stiffness
      measurement (LSM) has been accepted widely as a noninvasive assessment for liver
      fibrosis. We aimed to evaluate the usefulness of LSM in predicting PHLF. METHODS:
      One hundred seventy-seven patients with hepatocellular carcinoma who underwent
      liver resection between August 2011 and October 2014 were analyzed prospectively.
      LSM was performed by Virtual Touch Tissue Quantification based on acoustic
      radiation force impulse imaging, and its value was expressed as the shear wave
      velocity (Vs) [m/s]. The remnant liver volume rate (Rem) was calculated by
      computed tomography volumetry. PHLF was diagnosed on the basis of the definition
      from the International Study Group of Liver Surgery. RESULTS: PHLF occurred in 38
      patients (21.5%): grade A, 17 patients (9.6%); grade B, 15 patients (8.5%); and
      grade C, 6 patients (3.4%). The area under the receiver operating characteristic
      curve of the Vs for predicting PHLF was 0.67 for grade >=A, 0.78 for grade >=B,
      and 0.74 for grade C, which was greater than any other preoperative factor for
      each grade. Multivariate stepwise selection identified 2 significant factors
      associated with PHLF grade >=B: Vs (odds ratio, 2.66; 95% confidence interval,
      1.69-4.41, P < .01) and Rem (odds ratio, 0.47; 95% confidence interval, 0.27
      0.79, P < .01). The logistic model that included the Vs and Rem resulted in an
      area under the receiver operating characteristic curve of 0.80 for predicting
      PHLF grade >=B. CONCLUSION: LSM was useful for the prediction of PHLF and the
      estimation of the safe Rem range.

PMID- 26209568
TI  - Targeted nuclear factor-kappaB suppression enhances gemcitabine response in human
      pancreatic tumor cell line murine xenografts.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly fatal
      malignancy characterized by resistance to chemotherapy. Currently, gemcitabine is
      the agent used most commonly but demonstrates only a partial response. The
      transcription factor nuclear factor-kappaB (NF-kappaB), known to be involved in
      the inflammatory response, is constitutively activated in PDAC and further
      activated by gemcitabine. Our aim was to examine the effects of targeted NF
      kappaB suppression on gemcitabine resistance using an in vivo tumor growth model.
      METHODS: To suppress the NF-kappaB pathway, the mutant IkappaBalpha super
      repressor protein was stably expressed in PaCa-2 human PDAC cells. Athymic mice
      were injected subcutaneously with IkappaBalpha-super-repressor (SR) or vector
      expressing PaCa-2 cells and randomized to receive phosphate-buffered saline (PBS)
      or 100 mg/kg gemcitabine(gem) for 4 weeks. RESULTS: The mean increase in tumor
      volume was 47 mm(3) (89%) and 196 mm(3) (326%) in gem/SR and gem/vector groups,
      respectively (P = .03). The PBS-treated groups demonstrated greater tumor growth,
      ~340 mm(3) (850%) increase, in both PBS/vector and PBS/SR groups. Intratumoral NF
      kappaB activity was decreased in gem/SR compared with the gem/vector group (P =
      .04). Decreased Ki-67 positivity was noted in gem/SR (49%) versus gem/vector
      tumors (73%) (P = .04), with no difference in apoptosis (apoptag, P = .3) or
      angiogenesis (CD31+, P = .9). CONCLUSION: Stable IkappaBalpha-SR expression in
      vivo potentiated the antitumor effects of gemcitabine, resulting in decreased
      tumor growth in association with decreased cell proliferation. Molecular
      suppression of the NF-kappaB pathway decreases successfully gemcitabine
      resistance in a relatively chemoresistant PDAC line. Thus, NF-kappaB-targeted
      agents may complement gemcitabine-based therapies and decrease chemoresistance in
      patients with PDAC.

PMID- 26209569
TI  - Identification of behaviors and techniques for promoting autonomy in the
      operating room.
AB  - BACKGROUND: To further understand how faculty promote resident autonomy in the
      operating room (OR), we explored their perceptions, and those of senior
      residents, on the behaviors and techniques they employ to foster independence.
      METHODS: Twenty postgraduate year PGY4 and PGY5 residents were asked to list 3
      general surgery faculty who give the most and least autonomy to residents in the
      OR. Two focus groups were conducted with residents to identify behaviors and
      techniques for promoting autonomy from the resident perspective. Individual
      semistructured interviews were conducted with top-rated and low-rated faculty to
      identify behaviors and techniques from the attending perspective. RESULTS:
      Behaviors and techniques faculty exhibit to promote increased autonomy included
      allowing residents time to struggle, letting residents begin case themselves, and
      forcing residents to think about steps of procedure before case. The main
      "triggers" for granting autonomy were increased familiarity and trust with
      resident's capabilities, how well resident comes prepared to OR, and faculty
      confidence that they can "fix anything." Reasons why low-rated faculty seldom
      give autonomy included feeling a deep moral obligation for personally seeing
      patient through the operation, residents not coming fully prepared to perform
      case, and being young in their own maturation process. CONCLUSION: Our results
      suggest that increased autonomy depends greatly on establishing a trusting
      relationship between faculty and resident; a partnership that can only happen
      when time is given for trust to mature. Program directors must work to refine the
      training paradigm in order to build relationships. Residents can also be coached
      to demonstrate increased OR preparedness.

PMID- 26209571
TI  - Regarding 'Opportunity lost: Adjuvant chemotherapy in patients with Stage III
      colon cancer remains underused'.

PMID- 26209570
TI  - Daily propranolol prevents prolonged mobilization of hematopoietic progenitor
      cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress.
AB  - INTRODUCTION: Propranolol has been shown previously to decrease the mobilization
      of hematopoietic progenitor cells (HPCs) after acute injury in rodent models;
      however, this acute injury model does not reflect the prolonged period of
      critical illness after severe trauma. Using our novel lung contusion/hemorrhagic
      shock/chronic restraint stress model, we hypothesize that daily administration of
      propranolol will decrease prolonged mobilization of HPCs without worsening lung
      healing. METHODS: Male Sprague-Dawley rats underwent 6 days of restraint stress
      after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint
      stress consisted of a daily 2-hour period of restraint interrupted every 30
      minutes by alarms and repositioning. Each day after the period of restraint
      stress, the rats received intraperitoneal propranolol (10 mg/kg). On day 7,
      peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF)
      and stromal cell-derived factor 1 via enzyme-linked immunosorbent assay and for
      mobilization of HPCs using c-kit and CD71 flow cytometry. The lungs were examined
      histologically to grade injury. RESULTS: Seven days after lung contusion and lung
      contusion/hemorrhagic shock, the addition of chronic restraint stress
      significantly increased the mobilization of HPC, which was associated with
      persistently increased levels of G-CSF and increased lung injury scores. The
      addition of propranolol to lung contusion/chronic restraint stress and lung
      contusion/hemorrhagic shock/chronic restraint stress models greatly decreased HPC
      mobilization and restored G-CSF levels to that of naive animals without worsening
      lung injury scores. CONCLUSION: The daily administration of propranolol after
      both lung contusion and lung contusion/hemorrhagic shock subjected to chronic
      restraint stress decreased the prolonged mobilization of HPC from the bone marrow
      and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC,
      lung healing did not worsen. Alleviating chronic stress with propranolol may be a
      future therapeutic target to improve healing after severe injury.

PMID- 26209572
TI  - Splenectomy is associated with hypercoagulable thrombelastography values and
      increased risk of thromboembolism.
AB  - BACKGROUND: Previous investigators have demonstrated that postinjury
      thrombocytosis is associated with an increase in thromboembolic (TE) risk.
      Increased rates of thrombocytosis have been found specifically in patients after
      splenectomy for trauma. We hypothesized that patients undergoing splenectomy (1)
      would demonstrate a more hypercoagulable profile during their hospital stay and
      (2) that this hypercoagulable state would be associated with increased TE events.
      METHODS: This was a 14-month, prospective, observational trial evaluating serial
      rapid thrombelastography (rTEG) at 3 American College of Surgeons-verified, level
      1 trauma centers. Inclusion criteria were highest-level trauma activation and
      arrival within 6 hours of injury. Exclusion criteria were <18 years of age,
      incarcerated, and burns>20% total body surface area. Serial rTEG (activated
      clotting time, k-time, alpha-angle, MA, lysis) and traditional coagulation
      testing (prothrombin time, partial thromboplastin time, fibrinogen and platelet
      count) were obtained at admission and then at 3, 6, 12, 24, 48, 72, 96, and 120
      hours. Thromboembolic complications were defined as the development of deep-vein
      thrombosis, pulmonary embolism, acute myocardial infarction, or ischemic stroke
      during hospitalization. Patients were stratified into splenectomy versus
      nonsplenectomy cohorts. Univariate analysis was then conducted followed by
      longitudinal analysis using generalized estimating equations to evaluate the
      effects of time, splenectomy, and group-time interactions on changes in rTEG and
      traditional coagulation testing. We used an adjusted generalized estimating
      equation model to control for age, sex, ISS, admission blood pressure, base
      deficit, and hemoglobin. RESULTS: A total of 1,242 patients were enrolled; 795
      had serial rTEG data. Of these, 605 had serial values >24 hours and made up the
      study population. Splenectomy patients were younger, more hypotensive, and in
      shock on arrival. Although there was no difference in 24-hour or 30-day
      mortality, splenectomy patients were more likely to develop TE events. Using the
      GEE model, we found that alpha-angle and MA in splenectomy patients were lesser
      (more hypocoagulable) within the first 6 hours; however, they became
      substantially greater (more hypercoagulable) at 48, 72, 96, and 120 hours; all P
      < .05. In addition, platelet counts were greater in the splenectomy group
      beginning at 72 hours and continuing through 120 hours; P < .05. CONCLUSION: This
      multicenter, prospective study demonstrates that patients undergoing splenectomy
      have a more hypercoagulable state than other trauma patients. This
      hypercoagulable state (identified by greater alpha-angle and mA values) begins at
      approximately 48 hours after injury and continues through at least day 5.
      Moreover, this hypercoagulable state is associated with increased risk of TE
      complications.

PMID- 26209573
TI  - Implementation of a shared-savings program for surgical supplies decreases
      inventory cost.
AB  - BACKGROUND: Management of operating room inventory has substantial cost-saving
      opportunities if surgeons agree to standardize supplies used to perform
      procedures; however, there is no incentive for surgeons to participate in these
      decisions, because the cost-savings are realized only by the hospital, not the
      practitioner. In an attempt to engage surgeons with the management of the
      operating room supply chain, a shared-savings programs was instituted that
      returned 50% of money saved to the surgery divisions. METHODS: Opportunities for
      savings in the use of biologic mesh, cranial plating systems, and
      neurostimulators was identified. Each item was assigned a physician champion
      responsible for ensuring that there was clinical equipoise between the products
      being used. Any cost-savings realized during the fiscal year were shared 50-50
      between the hospital and the surgery divisions. RESULTS: The total cost-savings
      was $893,865 with $446,932 being shared across 15 surgery divisions.
      Standardization of cranial plating systems ($374,805) generated the greatest
      amounts of savings followed by neurostimulators ($278,404) and biologic mesh
      ($240,655). CONCLUSION: Aligning hospital and surgeon incentives led to dramatic
      cost-savings and standardization of the operative inventory used. Quality of care
      is not compromised by this approach, and no conflicts of interest are created.

PMID- 26209574
TI  - The role of the hospital and health care system characteristics in readmissions
      after major surgery in California.
AB  - BACKGROUND: Hospital readmission after major surgery is a costly problem that has
      been associated with patient characteristics. Because hospitals are incentivized
      to join accountable care organizations, interventions on a hospital or health
      care system level may help reduce readmissions. Our objective was to identify
      hospital- and systems-level characteristics associated with readmissions after
      major operative procedures. METHODS: Retrospective analysis of California
      discharge abstracts with record linkage numbers for adult patients undergoing
      coronary artery bypass graft (CABG), colectomy or total hip/knee arthroplasty
      (TJA) in California acute, nonfederal hospitals in 2011. The record linkage
      number showed where patients were readmitted. Hierarchic logistic regression
      estimated the odds of readmission by hospital characteristics. RESULTS: There
      were 91,205 records analyzed: CABG (6.4%), colectomy (12.0%), and TJA (82.3%).
      There were 120 hospitals that performed CABG surgery; 296 performed colectomy;
      and 298 performed TJA. Readmission rates after CABG was 9.7%, colectomy 7.7%, and
      TJA 3.9%. After adjustment for patient factors, rural location was predictive of
      readmission after colectomy (odds ratio [OR] 2.08, 95% confidence interval [CI]
      1.40-3.08). Low-volume (OR 1.54, 95% CI 1.13-2.10) and minority-serving hospitals
      (OR 1.18, 95% CI 1.05-1.33) were associated with greater odds of readmission
      after TJA. CONCLUSION: Select hospital characteristics are associated with
      readmissions after major operative procedures. Because financial penalties may
      worsen performance in vulnerable or low-resource settings, policies aimed at
      reducing readmissions should be attentive to the potential unintended
      consequences.

PMID- 26209576
TI  - Isolation of Methoxyfuranocoumarins From Ammi majus by Centrifugal Partition
      Chromatography.
AB  - Pure methoxyfuranocoumarins were isolated from Ammi majus L. by use of low
      pressure column chromatography (LPCC) followed by centrifugal partition
      chromatography (CPC). The concentrated petroleum ether extract from fruits of A.
      majus was fractionated on a silica gel column using a gradient of ethyl acetate
      in dichloromethane (0-80%, v/v). Coumarin-rich fractions were analyzed by thin
      layer chromatography (TLC) and high-performance liquid chromatography with diode
      array detection (HPLC/DAD). Xanthotoxin (8-MOP) and isopimpinellin (isoP),
      structurally similar compounds, were isolated in one fraction (FR6). To avoid
      multistep and long-lasting TLC preparation, optimization of CPC conditions has
      been performed. In one run, an effective separation of 8-MOP and isoP was
      achieved. The two-phase solvent system composed of n-hexane-ethyl acetate
      methanol-water (10 : 8 : 10 : 9; v/v) in an ascending mode (the aqueous phase was
      a stationary phase, and the organic phase was a mobile phase), with flow rate 3
      mL/min and rotation speed 1,600 r.p.m., was used. The identification and high
      purities of isolated 8-MOP (98.7%) and isoP (100%) were confirmed by HPLC/DAD
      assay, when compared with standards. The developed CPC method could be applied to
      the effective isolation of 8-MOP and isoP from plant extracts. The high purity of
      obtained compounds makes possible further exploitation of these components in
      biological studies. 

PMID- 26209577
TI  - Examination of near-wall hemodynamic parameters in the renal bridging stent of
      various stent graft configurations for repairing visceral branched aortic
      aneurysms.
AB  - OBJECTIVE: This study examined the flow behavior of four stent graft
      configurations for endovascular repair of complex aneurysms of the descending
      aorta. METHODS: Computational fluid dynamics models with transient boundary
      conditions and rigid wall simplifying assumptions were developed and used with
      four distinct geometries to compare various near-wall hemodynamic parameters.
      RESULTS: Graphic plots for time-averaged wall shear stress, oscillating shear
      index, and relative residence time were presented and compared among the four
      stent graft configurations of interest. CONCLUSIONS: Abrupt 90 degrees  and 180
      degrees  changes in stent geometry (particularly in the side branches) cause a
      high momentum change and thus increased flow separation and mixing, which has
      significant implications in blood flow characteristics near the wall. By
      comparison, longer bridging stents provide more gradual changes in momentum, thus
      allowing blood flow to develop before reaching the target vessel.

PMID- 26209578
TI  - Association between gender and outcomes of lower extremity peripheral vascular
      interventions.
AB  - OBJECTIVE: The purpose of this study was to evaluate the association of gender
      with outcomes of peripheral vascular intervention (PVI) for intermittent
      claudication and critical limb ischemia (CLI). METHODS: We reviewed 3338 patients
      (1316 [39%] women) undergoing PVI for claudication (1892; 57%) or CLI (1446; 43%)
      in the Vascular Study Group of New England from January 2010 to June 2012. Kaplan
      Meier analysis, stratified by indication, was used to assess relationships
      between gender and the main outcome measures of major amputation, reintervention,
      and survival during the first year. RESULTS: Indications for PVI included
      claudication (n = 719 [38%] vs n = 1173 [62%]) and CLI (n = 597 [41%] vs n = 849
      [59%]) in women and men, respectively (P = .0028). Women were older (69 vs 66
      mean years; P < .00001), with less diabetes (43% vs 49%; P = .01), renal
      insufficiency (4.6% vs 7.3%; P = .0029), coronary artery disease (28% vs 35%; P <
      .00001), smoking (76% vs 86%; P = .01), and statin use (60% vs 64%; P = .0058).
      Technical success (95% vs 94%; P = .11), vascular injury (1.3% vs 1.0%; P = .82),
      and distal embolization (1.6% vs 1.3%; P = .46) were similar. Higher rates of
      hematoma (7.1% vs 3.4%; P <= .0001) and access site occlusion (0.91% vs 0.24%; P
      = .0085) were observed in women compared with men. There were no differences in
      major amputation (0.6% vs 0.6%; P = .81) or mortality (2.1% vs 1.5%; P = .20)
      rates at 30 days between women and men. Reinterventions (surgical and
      percutaneous) were similar between genders for claudicants (log-rank test, P =
      .75) and CLI patients (log-rank test, P = .93). Major amputation rates during the
      first year were not different for women and men and with claudication (log-rank
      test, P < .55) or CLI (log-rank test, P < .23). One-year survival was not
      different between women and men with claudication (95% vs 96%; P = .19) or CLI
      (77% vs 79%; P = .35). CONCLUSIONS: Whereas we observed higher rates of access
      site complications including hematoma and occlusion in women, we found no other
      evidence for gender disparity in reinterventions, major amputation, or survival
      rates after PVI for patients with claudication or CLI.

PMID- 26209579
TI  - Concurrent hepatic hemangioma and solitary fibrous tumor: diagnosis and
      management.
AB  - Hepatic solitary fibrous tumor (HSFT) is a very rare benign liver tumor without
      well-defined findings on imaging. Even with multiphase advanced contrast-enhanced
      liver imaging, a definitive preoperative diagnosis is impossible. The diagnostic
      process can be further complicated when there are two concurrent lesions with
      different radiologic appearances. Here, we compare the findings of a commonly
      encountered liver lesion, hepatic hemangioma, with those of an exceedingly rare
      lesion, HSFT. 

PMID- 26209580
TI  - Statistical strategies and stochastic predictive models for the MARK-AGE data.
AB  - MARK-AGE aims at the identification of biomarkers of human aging capable of
      discriminating between the chronological age and the effective functional status
      of the organism. To achieve this, given the structure of the collected data, a
      proper statistical analysis has to be performed, as the structure of the data are
      non trivial and the number of features under study is near to the number of
      subjects used, requiring special care to avoid overfitting. Here we described
      some of the possible strategies suitable for this analysis. We also include a
      description of the main techniques used, to explain and justify the selected
      strategies. Among other possibilities, we suggest to model and analyze the data
      with a three step strategy. 

PMID- 26209581
TI  - The effect of pillow height on muscle activity of the neck and mid-upper back and
      patient perception of comfort.
AB  - OBJECTIVE: The purpose of this study was to evaluate the comfort and the
      electromyographic (EMG) activity of the neck and mid-upper back of asymptomatic
      adults using foam pillows of 3 different heights. METHODS: Twenty-one
      asymptomatic adults used foam pillows of 3 different heights (1: 5 cm, 2: 10 cm,
      and 3: 14 cm). Comfort was assessed using a 100-mm visual analog scale.
      Electromyographic activity was assessed in the lateral position. We calculated
      the root mean square (RMS) in 500-millisecond windows of bilateral EMG activity
      of the sternocleidomastoid and upper and middle trapezius, normalized by maximal
      isometric contraction of each individual. The RMS of the EMG signals was compared
      among pillow heights using repeated-measures analysis of variance (P < .05).
      RESULTS: The middle trapezius muscle of the down-side showed the highest RMS in
      height 1 when compared with heights 2 (P = .0163) and 3 (P = .0313), with no
      statistical significance between pillow heights 2 and 3 for this muscle. There
      were no statistical differences between pillows 2 and 3 in any muscle activity.
      Height 2 was considered the most comfortable (P < .001) compared with heights 1
      and 3, and height 1 the least comfortable (P < .001) compared with the other
      heights. CONCLUSION: For the participants in this study, there was an association
      among pillow height, myoelectric activity, and comfort.

PMID- 26209582
TI  - Test-retest reliability of trunk motor variability measured by large-array
      surface electromyography.
AB  - OBJECTIVE: The objective of this study was to evaluate the test-retest
      reliability of the trunk muscle activity distribution in asymptomatic
      participants during muscle fatigue using large-array surface electromyography
      (EMG). METHODS: Trunk muscle activity distribution was evaluated twice, with 3 to
      4 days between them, in 27 asymptomatic volunteers using large-array surface EMG.
      Motor variability, assessed with 2 different variables (the centroid coordinates
      of the root mean square map and the dispersion variable), was evaluated during a
      low back muscle fatigue task. Test-retest reliability of muscle activity
      distribution was obtained using Pearson correlation coefficients. RESULTS: A
      shift in the distribution of EMG amplitude toward the lateral-caudal region of
      the lumbar erector spinae induced by muscle fatigue was observed. Moderate to
      very strong correlations were found between both sessions in the last 3 phases of
      the fatigue task for both motor variability variables, whereas weak to moderate
      correlations were found in the first phases of the fatigue task only for the
      dispersion variable. CONCLUSION: These findings show that, in asymptomatic
      participants, patterns of EMG activity are less reliable in initial stages of
      muscle fatigue, whereas later stages are characterized by highly reliable
      patterns of EMG activity.

PMID- 26209583
TI  - The use of PermacolTM surgical implant for subxiphoid incisional hernia repair in
      cardiac transplant patients.

PMID- 26209584
TI  - Systemic inflammation in xenograft recipients (SIXR): A new paradigm in pig-to
      primate xenotransplantation?
AB  - Inflammation is a complex response that involves interactions between multiple
      proteins in the human body. The interaction between inflammation and coagulation
      is well-recognized, but its role in the dysregulation of coagulation in xenograft
      recipients is not well-understood. Additionally, inflammation is known to prevent
      the development of T cell tolerance after transplantation. Recent evidence
      indicates that systemic inflammation precedes and may be promoting activation of
      coagulation after pig-to-primate xenotransplantation. Activated recipient innate
      immune cells expressing tissue factor are increased after xenotransplantation,
      irrespective of immunosuppressive therapy. With immunosuppression, C-reactive
      protein (C-RP), fibrinogen, and interleukin-6 levels are significantly increased
      in pig artery patch recipients. In pig organ recipients, increased C-RP levels
      are observed prior to the development of features of consumptive coagulopathy.
      Systemic inflammation in xenograft recipients (Sixr) may be a key factor in the
      development of dysregulation of coagulation, as well as in resistance to
      immunosuppressive therapy. While genetic modification of the donor pigs provides
      protection against humoral responses and the development of thrombotic
      microangiopathy, therapeutic prevention of Sixr may be essential in order to
      prevent systemic dysregulation of coagulation in xenograft recipients without the
      use of intensive immunosuppression. 

PMID- 26209585
TI  - Immune enhancing nutrition in traumatic brain injury - A preliminary study.
AB  - Traumatic brain injury (TBI) is a major cause of death and disability worldwide.
      Certain patients appear to benefit when they receive immune enhancing additives,
      such as glutamine, arginine, and omega-3 fatty acids. We hypothesized that TBI
      patients given enteral feedings containing these supplements may have improved
      nutrition measures and infection rates when compared to standard tube feedings.
      This is a retrospective review of patients from a Level-One trauma center from
      July 2009 to July 2013. A total of 240 TBI patients received either an immune
      enhancing nutrition (IEN) formula (n = 126), or a standard formula (SF) (n = 114)
      based on the attending surgeon's preference. Data collected included demographic
      information, infection information and outcome measures. Patients were similar in
      terms of age, ISS, head AIS, and initial prealbumin level. Patients receiving IEN
      were found to have lower rates of blood stream infections (10.3% vs 19.3%, p <
      0.05), whereas pneumonia and UTI rates were similar between groups. In addition,
      both groups had similar rates of all-cause mortality and hospital length of stay,
      however IEN patients spent longer in the ICU and on ventilators. In TBI patients
      receiving IEN, prealbumin levels were higher at the second, third, and fourth
      week of admission (week 2 - 22.2 vs 17.4, p = 0.006; week 3 - 24.6 vs 20.1, p =
      0.04; week 4 - 26.3 vs 22.1, p = 0.19; week 5 - 25.8 vs 20.3, p = 0.21). This
      study suggests that patients with traumatic brain injury who receive IEN are more
      likely to have increased prealbumin levels perhaps reflecting improved nutrition
      throughout their hospital stay and may show some benefit in rates of infections,
      particularly in bacteremia.

PMID- 26209586
TI  - Optic neuropathy in methylmalonic acidemia and propionic acidemia.
AB  - BACKGROUND: Methylmalonic acidemia (MMA) and propionic acidemia (PA) are rare
      hereditary disorders of protein metabolism, manifesting early in life with
      ketoacidosis and encephalopathy and often resulting in chronic complications.
      Optic neuropathy (ON) has been increasingly recognised in both conditions, mostly
      through isolated case reports or small cases series. We here report the clinical
      features and visual outcomes of a case series of paediatric patients with a
      diagnosis of MMA or PA. METHODS: Retrospective observational case series. A
      database of patients attending the Willink Biochemical Genetics unit in
      Manchester was interrogated. Fifty-three patients had a diagnosis of either
      isolated MMA or PA, of which 12 had been referred for ophthalmic review. RESULTS:
      Seven patients had clinical findings compatible with ON. Visual outcomes in these
      patients were poor, with slow clinical progression or stability over time in five
      cases with follow-up. Presentation was acute in a context of metabolic crisis in
      two of the cases. Four patients with ON had electrodiagnostics showing absent
      pattern evoked potentials, with one showing a preserved flash response. All four
      showed marked attenuation of the dark-adapted electroretinogram with better
      preservation of the light-adapted response. CONCLUSIONS: Our study suggests that
      ON is under-reported in patients with MMA and PA. Clinical presentation can be
      acute or insidious, and episodes of acute metabolic decompensation appear to
      trigger visual loss. Photoreceptor involvement may coexist. Active clinical
      surveillance of affected patients is important as comorbidities and cognitive
      impairment may delay diagnosis.

PMID- 26209587
TI  - Fixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day,
      randomised, controlled study in patients with open-angle glaucoma or ocular
      hypertension.
AB  - BACKGROUND/AIMS: To evaluate the ocular hypotensive efficacy of fixed-dose
      combinations of the Rho kinase inhibitor and norepinephrine transport inhibitor
      AR-13324 (0.01% and 0.02%) and latanoprost (PG324 Ophthalmic Solution) relative
      to the active components AR-13324 0.02% and latanoprost 0.005%, used bilaterally
      at night. METHODS: This was a double-masked, randomised, parallel comparison
      study in patients with open-angle glaucoma or ocular hypertension. After washout,
      patients were randomised to one of four treatment arms and treated for 28 days.
      The primary efficacy variable was mean diurnal intraocular pressure (IOP) at day
      29. RESULTS: We randomised 298 patients, of whom 292 (98%) completed the study.
      Mean unmedicated diurnal IOPs (study eye) was 25.1, 25.1, 26.0 and 25.4 in the
      PG324 0.01%, PG324 0.02%, latanoprost and AR-13324 0.02% groups, respectively. On
      day 29, mean diurnal IOP decreased to 17.3, 16.5, 18.4 and 19.1 mm Hg,
      respectively. For the primary efficacy variable of mean diurnal IOP at day 29,
      PG324 0.02% met the criterion for statistical superiority relative to both
      latanoprost and AR-13324 0.02% (p<0.0001), providing additional IOP lowering of
      1.9 and 2.6 mm Hg, respectively. PG324 0.01% also met the criterion for
      superiority. The most frequently reported adverse event was conjunctival
      hyperaemia with an incidence of 41% (30/73), 40% (29/73), 14% (10/73) and 40%
      (31/78) in the PG324 0.01%, PG324 0.02%, latanoprost and AR-13324 0.02% groups,
      respectively. CONCLUSIONS: In this short-term study, the fixed-dose combination
      of AR-13324 0.02% and latanoprost 0.005% in PG324 Ophthalmic Solution provides
      clinically and statistically superior ocular hypotensive efficacy relative to its
      individual active components at the same concentrations. The only safety finding
      of note was transient asymptomatic conjunctival hyperaemia which was typically of
      mild severity. TRIAL REGISTRATION NUMBER: NCT02057575.

PMID- 26209588
TI  - Differentiating neuromyelitis optica from other causes of longitudinally
      extensive transverse myelitis on spinal magnetic resonance imaging.
AB  - BACKGROUND: Although spinal magnetic resonance imaging (MRI) findings of
      neuromyelitis optica (NMO) have been described, there is limited data available
      that help differentiate NMO from other causes of longitudinally extensive
      transverse myelitis (LETM). OBJECTIVE: To investigate the spinal MRI findings of
      LETM that help differentiate NMO at the acute stage from multiple sclerosis (MS)
      and other causes of LETM. METHODS: We enrolled 94 patients with LETM into our
      study. Bright spotty lesions (BSL), the lesion distribution and location were
      evaluated on axial T2-weighted images. Brainstem extension, cord expansion, T1
      darkness and lesion enhancement were noted. We also reviewed the brain MRI of the
      patients during LETM. RESULTS: Patients with NMO had a greater amount of BSL and
      T1 dark lesions (p < 0.001 and 0.003, respectively). The lesions in NMO patients
      were more likely to involve greater than one-half of the spinal cord's cross
      sectional area; to enhance and be centrally-located, or both centrally- and
      peripherally-located in the cord. Of the 62 available brain MRIs, 14 of the 27
      whom were NMO patients had findings that may be specific to NMO. CONCLUSIONS:
      Certain spinal cord MRI features are more commonly seen in NMO patients and so
      obtaining brain MRI during LETM may support diagnosis.

PMID- 26209589
TI  - Outer retinal changes following acute optic neuritis.
AB  - BACKGROUND: Retinal nerve fiber and ganglion cell+inner plexiform (GCIP) layer
      thinning following multiple sclerosis-related acute optic neuritis (AON) is well
      described. However, whether AON results in changes in the inner nuclear (INL),
      outer plexiform (OPL), outer nuclear (ONL) and/or photoreceptor segment (PS)
      layers remains undetermined. OBJECTIVES: The objective of this paper is to
      determine if INL+OPL and/or ONL+PS changes occur following AON. METHODS: Thirty
      three AON patients underwent serial optical coherence tomography (OCT) and visual
      function testing (mean follow-up: 25 months). Longitudinal changes in retinal
      layer thickness were analyzed using mixed-effects linear regression. RESULTS:
      Four months following AON, the mean decrease in GCIP thickness relative to
      baseline was 11.4% (p < 0.001). At four months, a concomitant 3.4% increase in
      average ONL+PS thickness was observed (p < 0.001). The percentage decrease in
      GCIP thickness and increase in ONL+PS thickness were strongly correlated (r = 
      0.70; p < 0.001). Between months 4 to 12, ONL+PS thickness declined and, at 12
      months, was no longer significantly different from baseline (mean change: 0.5%; p
      = 0.37). Similar, albeit less robust, changes in the INL+OPL were observed.
      CONCLUSIONS: Following AON, dynamic changes occur in the deep retinal layers,
      which are proportional to GCIP thinning. These novel findings help further our
      understanding of the biological and/or anatomical sequelae resulting from AON.

PMID- 26209590
TI  - Are Leber's mitochondial DNA mutations associated with aquaporin-4 autoimmunity?

PMID- 26209591
TI  - Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis at
      7T.
AB  - BACKGROUND: The clinical course of multiple sclerosis (MS) is mainly attributable
      to cervical and upper thoracic spinal cord dysfunction. High-resolution, 7T
      anatomical imaging of the cervical spinal cord is presented. Image contrast
      between gray/white matter and lesions surpasses conventional, clinical T1- and T2
      weighted sequences at lower field strengths. OBJECTIVE: To study the spinal cord
      of healthy controls and patients with MS using magnetic resonance imaging at 7T.
      METHODS: Axial (C2-C5) T1- and T2*-weighted and sagittal T2*-/spin-density
      weighted images were acquired at 7T in 13 healthy volunteers (age 22-40 years),
      and 15 clinically diagnosed MS patients (age 19-53 years, Extended Disability
      Status Scale, (EDSS) 0-3) in addition to clinical 3T scans. In healthy
      volunteers, a high-resolution multi-echo gradient echo scan was obtained over the
      same geometry at 3T. Evaluation included signal and contrast to noise ratios and
      lesion counts for healthy and patient volunteers, respectively.
      RESULTS/CONCLUSION: High-resolution images at 7T exceeded resolutions reported at
      lower field strengths. Gray and white matter were sharply demarcated and MS
      lesions were more readily visualized at 7T compared to clinical acquisitions,
      with lesions apparent at both fields. Nerve roots were clearly visualized. White
      matter lesion counts averaged 4.7 vs 3.1 (52% increase) per patient at 7T vs 3T,
      respectively (p=0.05).

PMID- 26209592
TI  - Antibodies to myelin oligodendrocyte glycoprotein in aquaporin 4 antibody
      seronegative longitudinally extensive transverse myelitis: Clinical and
      prognostic implications.
AB  - OBJECTIVE: We aimed to investigate the frequency and clinical significance of
      antibodies to myelin oligodendrocyte glycoprotein (MOG-abs) in patients who
      presented with a first episode of seronegative aquaporin 4 antibody (AQP4-ab)
      longitudinally extensive transverse myelitis (LETM). METHODS: Epidemiological,
      clinical, and paraclinical data of 56 patients from three European centres were
      analysed. Patients were retrospectively tested for MOG-abs and AQP4-abs, by cell
      based assays. FINDINGS: Thirteen (23.2%) patients were MOG-ab positive. Among the
      56 patients, six (10.7%) converted to neuromyelitis optica (NMO), one (1.8%) to
      multiple sclerosis (MS), nine (16.1%) had recurrent LETM, and 40 (71.4%) remained
      as monophasic LETM. Compared with seronegative patients, those with MOG-abs were
      younger (median: 32.5 vs 44 years; p=0.007), had cerebrospinal fluid pleocytosis
      more frequently (94% vs 45%, p=0.003) and had better outcome (median Expanded
      Disability Status Scale (EDSS) 2.0 vs 3.0, p=0.027). MOG-ab positive patients
      also showed an increase risk of optic neuritis relapse and NMO conversion
      (p=0.010). CONCLUSION: Patients with MOG-abs in AQP4-ab seronegative LETM have
      clinical distinctive features, higher risk of optic neuritis relapses, and better
      outcome than patients seronegative.

PMID- 26209593
TI  - Multi-parametric structural magnetic resonance imaging in relation to cognitive
      dysfunction in long-standing multiple sclerosis.
AB  - BACKGROUND: Cognitive deficits are common in multiple sclerosis. Most previous
      studies investigating the imaging substrate of cognitive deficits in multiple
      sclerosis included patients with relatively short disease durations and were
      limited to one modality/brain region. OBJECTIVE: To identify the strongest
      neuroimaging predictors for cognitive dysfunction in a large cohort of patients
      with long-standing multiple sclerosis. METHODS: Extensive neuropsychological
      testing and multimodal 3.0T MRI was performed in 202 patients with multiple
      sclerosis and 52 controls. Cognitive scores were compared between groups using Z
      scores. Whole-brain, white matter, grey matter, deep grey matter and lesion
      volumes; cortical thickness, (juxta)cortical and cerebellar lesions; and extent
      and severity of diffuse white matter damage were measured. Stepwise linear
      regression was used to identify the strongest predictors for cognitive
      dysfunction. RESULTS: All cognitive domains were affected in patients. Patients
      showed extensive atrophy, focal pathology and damage in up to 75% of the
      investigated white matter. Associations between imaging markers and average
      cognition were two times stronger in cognitively impaired patients than in
      cognitively preserved patients. The final model for average cognition consisted
      of deep grey matter DGMV volume and fractional anisotropy severity (adjusted
      R2=0.490; p<0.001). CONCLUSION: From all imaging markers, deep grey matter
      atrophy and diffuse white matter damage emerged as the strongest predictors for
      cognitive dysfunction in long-standing multiple sclerosis.

PMID- 26209594
TI  - Validation of Computational Studies for Electrical Brain Stimulation With Phantom
      Head Experiments.
AB  - BACKGROUND: Although computational studies of electrical brain stimulation (EBS)
      have received attention as a cost-effective tool, few studies have validated the
      technique, particularly in invasive cortical stimulation. OBJECTIVE: In order to
      validate such studies, we used EBS to compare electric potential distributions
      generated by both numerical simulations and empirical measurements in three
      phantom head models (one-/three-layered spherical heads and MRI-based head).
      METHODS: We constructed spherical phantom heads that consisted of one or three
      layers, and an anatomical, MRI-based phantom that consisted of three layers and
      represented the brain or brain/skull/scalp in order to perform both numerical
      simulations using the finite element method (FEM) and experimental measurements.
      Two stimulation electrodes (cathode and anode) were implanted in the phantoms to
      inject regulated input voltage, and the electric potential distributions induced
      were measured at various points located either on the surface or deep within the
      phantoms. RESULTS: We observed that both the electric potential distributions
      from the numerical simulations and experiments behaved similarly and resulted in
      average relative differences of 5.4% (spherical phantom) and 10.3% (MRI-based
      phantom). CONCLUSIONS: This study demonstrated that numerical simulation is
      reasonably consistent with actual experimental measurements; thus, because of its
      cost-effectiveness, EBS computational studies may be an attractive approach for
      necessary intensive/extensive studies.

PMID- 26209595
TI  - Social Desirability Bias in Self-Reporting of Hearing Protector Use among Farm
      Operators.
AB  - OBJECTIVE: The purposes of this study were (i) to examine the relationship
      between reported hearing protector use and social desirability bias, and (ii) to
      compare results of the Marlowe-Crowne social desirability instrument when
      administered using two different methods (i.e. online and by telephone). METHODS:
      A shortened version of the Marlowe-Crowne social desirability instrument, as well
      as a self-administered instrument measuring use of hearing protectors, was
      administered to 497 participants in a study of hearing protector use. The
      relationship between hearing protector use and social desirability bias was
      examined using regression analysis. The results of two methods of administration
      of the Marlowe-Crowne social desirability instrument were compared using t-tests
      and regression analysis. RESULTS: Reliability (using Cronbach's alpha) for the
      shortened seven-item scale for this sample was 0.58. There was no evidence of a
      relationship between reported hearing protector use and social desirability
      reporting bias, as measured by the shortened Marlowe-Crowne. The difference in
      results by method of administration (i.e. online, telephone) was very small.
      CONCLUSIONS: This is the first published study to measure social desirability
      bias in reporting of hearing protector use among farmers. Findings of this study
      do not support the presence of social desirability bias in farmers' reporting of
      hearing protector use, lending support for the validity of self-report in hearing
      protector use in this population.

PMID- 26209596
TI  - Evaluation of Quantitative Exposure Assessment Method for Nanomaterials in Mixed
      Dust Environments: Application in Tire Manufacturing Facilities.
AB  - Current recommendations for nanomaterial-specific exposure assessment require
      adaptation in order to be applied to complicated manufacturing settings, where a
      variety of particle types may contribute to the potential exposure. The purpose
      of this work was to evaluate a method that would allow for exposure assessment of
      nanostructured materials by chemical composition and size in a mixed dust
      setting, using carbon black (CB) and amorphous silica (AS) from tire
      manufacturing as an example. This method combined air sampling with a low
      pressure cascade impactor with analysis of elemental composition by size to
      quantitatively assess potential exposures in the workplace. This method was first
      pilot-tested in one tire manufacturing facility; air samples were collected with
      a Dekati Low Pressure Impactor (DLPI) during mixing where either CB or AS were
      used as the primary filler. Air samples were analyzed via scanning transmission
      electron microscopy (STEM) coupled with energy dispersive spectroscopy (EDS) to
      identify what fraction of particles were CB, AS, or 'other'. From this pilot
      study, it was determined that ~95% of all nanoscale particles were identified as
      CB or AS. Subsequent samples were collected with the Dekati Electrical Low
      Pressure Impactor (ELPI) at two tire manufacturing facilities and analyzed using
      the same methodology to quantify exposure to these materials. This analysis
      confirmed that CB and AS were the predominant nanoscale particle types in the
      mixing area at both facilities. Air concentrations of CB and AS ranged from ~8900
      to 77600 and 400 to 22200 particles cm(-3), respectively. This method offers the
      potential to provide quantitative estimates of worker exposure to nanoparticles
      of specific materials in a mixed dust environment. With pending development of
      occupational exposure limits for nanomaterials, this methodology will allow
      occupational health and safety practitioners to estimate worker exposures to
      specific materials, even in scenarios where many particle types are present.

PMID- 26209597
TI  - Aerosol Emission Monitoring and Assessment of Potential Exposure to Multi-walled
      Carbon Nanotubes in the Manufacture of Polymer Nanocomposites.
AB  - Recent animal studies have shown that carbon nanotubes (CNTs) may pose a
      significant health risk to those exposed in the workplace. To further understand
      this potential risk, effort must be taken to measure the occupational exposure to
      CNTs. Results from an assessment of potential exposure to multi-walled carbon
      nanotubes (MWCNTs) conducted at an industrial facility where polymer
      nanocomposites were manufactured by an extrusion process are presented. Exposure
      to MWCNTs was quantified by the thermal-optical analysis for elemental carbon
      (EC) of respirable dust collected by personal sampling. All personal respirable
      samples collected (n = 8) had estimated 8-h time weighted average (TWA) EC
      concentrations below the limit of detection for the analysis which was about one
      half of the recommended exposure limit for CNTs, 1 ug EC/m(3) as an 8-h TWA
      respirable mass concentration. Potential exposure sources were identified and
      characterized by direct-reading instruments and area sampling. Area samples
      analyzed for EC yielded quantifiable mass concentrations inside an enclosure
      where unbound MWCNTs were handled and near a pelletizer where nanocomposite was
      cut, while those analyzed by electron microscopy detected the presence of MWCNTs
      at six locations throughout the facility. Through size selective area sampling it
      was identified that the airborne MWCNTs present in the workplace were in the form
      of large agglomerates. This was confirmed by electron microscopy where most of
      the MWCNT structures observed were in the form of micrometer-sized ropey
      agglomerates. However, a small fraction of single, free MWCNTs was also observed.
      It was found that the high number concentrations of nanoparticles, ~200000
      particles/cm(3), present in the manufacturing facility were likely attributable
      to polymer fumes produced in the extrusion process.

PMID- 26209598
TI  - A Comparison of the beta-Substitution Method and a Bayesian Method for Analyzing
      Left-Censored Data.
AB  - Classical statistical methods for analyzing exposure data with values below the
      detection limits are well described in the occupational hygiene literature, but
      an evaluation of a Bayesian approach for handling such data is currently lacking.
      Here, we first describe a Bayesian framework for analyzing censored data. We then
      present the results of a simulation study conducted to compare the beta
      substitution method with a Bayesian method for exposure datasets drawn from
      lognormal distributions and mixed lognormal distributions with varying sample
      sizes, geometric standard deviations (GSDs), and censoring for single and
      multiple limits of detection. For each set of factors, estimates for the
      arithmetic mean (AM), geometric mean, GSD, and the 95th percentile (X0.95) of the
      exposure distribution were obtained. We evaluated the performance of each method
      using relative bias, the root mean squared error (rMSE), and coverage (the
      proportion of the computed 95% uncertainty intervals containing the true value).
      The Bayesian method using non-informative priors and the beta-substitution method
      were generally comparable in bias and rMSE when estimating the AM and GM. For the
      GSD and the 95th percentile, the Bayesian method with non-informative priors was
      more biased and had a higher rMSE than the beta-substitution method, but use of
      more informative priors generally improved the Bayesian method's performance,
      making both the bias and the rMSE more comparable to the beta-substitution
      method. An advantage of the Bayesian method is that it provided estimates of
      uncertainty for these parameters of interest and good coverage, whereas the beta
      substitution method only provided estimates of uncertainty for the AM, and
      coverage was not as consistent. Selection of one or the other method depends on
      the needs of the practitioner, the availability of prior information, and the
      distribution characteristics of the measurement data. We suggest the use of
      Bayesian methods if the practitioner has the computational resources and prior
      information, as the method would generally provide accurate estimates and also
      provides the distributions of all of the parameters, which could be useful for
      making decisions in some applications. 

PMID- 26209599
TI  - Restrictive ring annuloplasty for chronic ischemic mitral regurgitation.

PMID- 26209600
TI  - Restrictive mitral annuloplasty plus posterior leaflet segment P2 plication.

PMID- 26209601
TI  - A rat model of aortic arch aneurysm with excellent survival.

PMID- 26209602
TI  - Fate of allogenic bone graft for sternal support in pectus excavatum repair.
AB  - BACKGROUND: Techniques for pectus excavatum repair are based on sternal support
      using various implants that have been reported to cause complications including
      migration and perforation of adjacent vital organs. Thus the search for an ideal
      sternal support is ongoing. This study aimed to assess the feasibility and fate
      of allogenic bone grafts as a durable sternal support for pectus excavatum
      repair. METHODS: Pectus excavatum deformities in 3 men were corrected by modified
      Ravitch repair using allogeneic bone grafts for sternal support. Postoperatively,
      the patients were followed up for 3 years. Chest computed tomography and bone
      scans were performed to identify radiological features relevant to the stability,
      viability, and fate of the bone grafts. RESULTS: The postoperative course was
      uneventful in all patients. Cosmetic correction was rated as very good with
      patient satisfaction. Bone scans showed progressively increasing activity in the
      graft, indicating an ongoing process of neovascularization. Chest computed
      tomography showed not only bone resorption, new bone formation, and remodeling
      but also incorporation of the graft into the sternum and corresponding ribs
      through newly generated, normally configured sternocostal segments. CONCLUSIONS:
      As seen radiologically, this technique offers a model for sternal support that
      has the potential to incorporate into the host tissue through newly generated,
      normally configured sternocostal segments, without restriction of chest wall
      expansion, features that have not been previously reported.

PMID- 26209603
TI  - Hyperhemolysis in Patients With Hemoglobinopathies: A Single-Center Experience
      and Review of the Literature.
AB  - Hyperhemolysis is a severe and potentially life-threatening complication of
      transfusion described in numerous case reports and gaining recognition since 2009
      via the UK Serious Hazards of Transfusion scheme. Although it is predominantly
      seen in patients with sickle cell disease, there are several reports of this
      complication in patients with other hemoglobinopathies as well as patients with a
      range of other hematologic diagnoses who have blood transfusions as part of their
      management. Our understanding of the underlying pathophysiology of this subtype
      of delayed transfusion reaction has increased over the last few years; however,
      there are still questions, which remain unanswered. In our center alone, we have
      encountered 9 cases in the last 5 years both in the adult and pediatric
      population. Here we discuss our experience in the diagnosis and management of
      this complication, and review other cases reported in the literature and the
      various existing theories behind the pathophysiology of this process. We also
      discuss the role of genotyping and using DNA technology to aid selection of the
      most appropriate blood for this patient group. With an increased awareness of
      hyperhemolysis, it would be advantageous to finally develop international
      registries to determine the true incidence of hyperhemolysis, better understand
      the pathophysiology, identify markers to predict which patients are at risk, and
      inform management guidelines. 

PMID- 26209604
TI  - Information/Education Page. Evaluating Your Pressure Ulcer Prevention Plan: A
      problem-solving worksheet for people with spinal cord injury and their health
      care providers.

PMID- 26209605
TI  - Effects of cilengitide in osteoclast maturation and behavior.
AB  - Bone metastasis is a common burden in many types of cancer and has a severe
      impact on the quality of life in patients. Hence, specific therapeutic strategies
      inhibiting tumor induced osteolysis are urgently needed. In this study, we aimed
      to interfere with integrin adhesion receptors, which are central players of the
      bone resorption process. For this purpose, we used cilengitide, a cyclic RGD
      peptide, which blocks integrin alphaVbeta3 and alphaVbeta5-ligand binding. Our
      results revealed that cilengitide blocked osteoclast maturation in a dose
      dependent manner. In detail, pre-osteoclasts treated with cilengitide exhibited
      reduced cell spreading, cell migration and cell adhesion on RGD-containing matrix
      proteins, which are ligands of integrin alphaV. The activation of the most
      upstream signal transduction molecules of the integrin receptor-initiated
      pathway, FAK and c-Src, were consistently blocked by cilengitide. First evidence
      suggests that cilengitide might interfere with metastatic bone disease in vivo
      and this study describes a potential underlying mechanism of the inhibitory
      effect of cilengitide on alphaV-integrin expressing pre-osteoclasts by blocking
      integrin ligand binding and interfering with osteoclast maturation and cell
      behavior. In conclusion, our findings suggest that cilengitide, which interferes
      with alphaV-integrins on osteoclasts, may represent a novel therapeutic strategy
      in the treatment of malignant bone disease.

PMID- 26209606
TI  - Suppressors of cytokine signaling 3 is essential for FcgammaR-mediated
      inflammatory response via enhancing CCAAT/enhancer-binding protein delta
      transcriptional activity in macrophages.
AB  - Compelling evidence indicates that suppressor of cytokine signaling 3 (SOCS3)
      plays a pivotal regulatory role in inflammation. However, the function of SOCS3
      in inflammatory responses mediated by Fcgamma receptor (FcgammaR) remains largely
      unknown. In the current study, we found that SOCS3 expression was greatly
      enhanced in peritoneal macrophages treated with IgG immune complex (IgG IC). By
      over-expressing SOCS3 in macrophages, we observed that SOCS3 promoted IgG immune
      complex-induced production of inflammatory mediators, including IL-6, TNF-alpha,
      MIP-2, and MIP-1alpha. In contrast, SOCS3-defective peritoneal macrophages
      generated less inflammatory cytokines and chemokines when compared with their
      wild type counterparts during IgG IC-induced inflammatory responses. We further
      demonstrated that CCAAT/enhancer-binding protein (C/EBP) delta transcription
      factor was the major downstream target of SOCS3 in macrophages. These data
      suggested that SOCS3 was an inflammatory enhancer in IgG IC-treated macrophages
      by increasing C/EBPdelta activity. To elucidate the role for myeloid-derived
      SOCS3 in IgG IC-induced inflammation in vivo, LysM-cre SOCS3(fl/fl) mice lacking
      SOCS3 in macrophages and neutrophils were generated. We found that SOCS3
      deficiency greatly alleviated IgG IC-induced generation of pro-inflammatory
      mediators in lungs, consistent with the in vitro data. Our current findings may
      provide a new theoretical basis for designing drugs for treatment of IgG IC
      associated diseases.

PMID- 26209607
TI  - Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of
      epithelial ovarian cancer.
AB  - Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor
      microenvironment. However, whether ADSCs have a hand in ovarian cancer
      progression remains unclear. In this study, we investigated the impact of human
      ADSCs derived from the omentum of normal donors on human epithelial ovarian
      cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models
      including ADSCs and human EOC cell lines were established and the effects of
      ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow
      cytometry. Transwell migration assays and detection of MMPs were performed to
      assess the invasion activity of EOC cells in vitro. Mouse models were established
      by intraperitoneal injection of EOC cells with or without concomitant ADSCs to
      investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs
      significantly promoted proliferation and invasion of EOC cells in both direct and
      indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells
      secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of
      MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro.
      In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and
      metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate
      that omental ADSCs play a promotive role during ovarian cancer progression.

PMID- 26209608
TI  - Quantitative Mass Spectrometry Reveals that Intact Histone H1 Phosphorylations
      are Variant Specific and Exhibit Single Molecule Hierarchical Dependence.
AB  - Breast cancer was the second leading cause of cancer related mortality for
      females in 2014. Recent studies suggest histone H1 phosphorylation may be useful
      as a clinical biomarker of breast and other cancers because of its ability to
      recognize proliferative cell populations. Although monitoring a single
      phosphorylated H1 residue is adequate to stratify high-grade breast tumors,
      expanding our knowledge of how H1 is phosphorylated through the cell cycle is
      paramount to understanding its role in carcinogenesis. H1 analysis by bottom-up
      MS is challenging because of the presence of highly homologous sequence variants
      expressed by most cells. These highly basic proteins are difficult to analyze by
      LC-MS/MS because of the small, hydrophilic nature of peptides produced by tryptic
      digestion. Although bottom-up methods permit identification of several H1
      phosphorylation events, these peptides are not useful for observing the
      combinatorial post-translational modification (PTM) patterns on the protein of
      interest. To complement the information provided by bottom-up MS, we utilized a
      top-down MS/MS workflow to permit identification and quantitation of H1
      proteoforms related to the progression of breast cells through the cell cycle.
      Histones H1.2 and H1.4 were observed in MDA-MB-231 metastatic breast cells,
      whereas an additional histone variant, histone H1.3, was identified only in
      nonneoplastic MCF-10A cells. Progressive phosphorylation of histone H1.4 was
      identified in both cell lines at mitosis (M phase). Phosphorylation occurred
      first at S172 followed successively by S187, T18, T146, and T154. Notably,
      phosphorylation at S173 of histone H1.2 and S172, S187, T18, T146, and T154 of
      H1.4 significantly increases during M phase relative to S phase, suggesting that
      these events are cell cycle-dependent and may serve as markers for proliferation.
      Finally, we report the observation of the H1.2 SNP variant A18V in MCF-10A cells.

PMID- 26209609
TI  - Systematic Determination of Human Cyclin Dependent Kinase (CDK)-9 Interactome
      Identifies Novel Functions in RNA Splicing Mediated by the DEAD Box (DDX)-5/17
      RNA Helicases.
AB  - Inducible transcriptional elongation is a rapid, stereotypic mechanism for
      activating immediate early immune defense genes by the epithelium in response to
      viral pathogens. Here, the recruitment of a multifunctional complex containing
      the cyclin dependent kinase 9 (CDK9) triggers the process of transcriptional
      elongation activating resting RNA polymerase engaged with innate immune response
      (IIR) genes. To identify additional functional activity of the CDK9 complex, we
      conducted immunoprecipitation (IP) enrichment-stable isotope labeling LC-MS/MS of
      the CDK9 complex in unstimulated cells and from cells activated by a synthetic
      dsRNA, polyinosinic/polycytidylic acid [poly (I:C)]. 245 CDK9 interacting
      proteins were identified with high confidence in the basal state and 20 proteins
      in four functional classes were validated by IP-SRM-MS. These data identified
      that CDK9 interacts with DDX 5/17, a family of ATP-dependent RNA helicases,
      important in alternative RNA splicing of NFAT5, and mH2A1 mRNA two proteins
      controlling redox signaling. A direct comparison of the basal versus activated
      state was performed using stable isotope labeling and validated by IP-SRM-MS.
      Recruited into the CDK9 interactome in response to poly(I:C) stimulation are
      HSPB1, DNA dependent kinases, and cytoskeletal myosin proteins that exchange with
      60S ribosomal structural proteins. An integrated human CDK9 interactome map was
      developed containing all known human CDK9- interacting proteins. These data were
      used to develop a probabilistic global map of CDK9-dependent target genes that
      predicted two functional states controlling distinct cellular functions, one
      important in immune and stress responses. The CDK9-DDX5/17 complex was shown to
      be functionally important by shRNA-mediated knockdown, where differential
      accumulation of alternatively spliced NFAT5 and mH2A1 transcripts and alterations
      in downstream redox signaling were seen. The requirement of CDK9 for DDX5
      recruitment to NFAT5 and mH2A1 chromatin target was further demonstrated using
      chromatin immunoprecipitation (ChIP). These data indicate that CDK9 is a dynamic
      multifunctional enzyme complex mediating not only transcriptional elongation, but
      also alternative RNA splicing and potentially translational control. 

PMID- 26209611
TI  - A before and after study of warfarin monitoring in a single region as part of the
      Scottish patient safety programme in primary care.
AB  - INTRODUCTION: Warfarin is an effective drug for patients at risk of
      thromboembolic events, but sub-optimal pharmacological management may cause
      significant harm. As part of the Scottish patient safety programme in primary
      care, one health board region aimed to determine if the international normalised
      ratio control for patients taking warfarin in general practice improved over the
      first 12 months of participation. METHODS: A before and after study of a multi
      intervention improvement strategy was employed that combined financial
      incentivisation, a regional learning collaborative, clinical care bundle
      implementation, audit and feedback and clinical 'safety champions'. The main
      patient outcome measures were: mean time in therapeutic range; proportion with
      good control (time in therapeutic range >60%) and excellent control (time in
      therapeutic range > 75%); and the proportion of very abnormal results
      (international normalised ratio < 1.5 or >5). Chi-square tests were used to
      determine statistical differences. RESULTS: In total, 49 of 55 general practices
      participated (89%) with 33/55 providing usable data (60%) on 1480 patients
      (before) and 1946 patients (after), respectively. Improvements were observed in
      mean time in therapeutic range (P < 0.05) as well as in the proportion of
      patients with good control (time in therapeutic range > 60%, P < 0.01) and
      excellent control (time in therapeutic range > 75%, P = 0.06). A reduction in the
      proportion of very abnormal results (international normalised ratio < 1.5 or >5)
      was also observed (P < 0.01), while the mean number of patient attendances
      reduced (P < 0.05). CONCLUSIONS: The introduction of a complex safety improvement
      intervention via a national patient safety programme has resulted in modest
      improvements in the control of warfarin monitoring in a single region. These
      improvements may potentially reduce the incidence of serious adverse events. The
      study method, interventions and findings should be of interest to primary care
      settings with similar warfarin management arrangements internationally.

PMID- 26209610
TI  - Prediction of Recurrence and Survival for Triple-Negative Breast Cancer (TNBC) by
      a Protein Signature in Tissue Samples.
AB  - To date, there is no available targeted therapy for patients who are diagnosed
      with triple-negative breast cancers (TNBC). The aim of this study was to identify
      a new specific target for specific treatments. Frozen primary tumors were
      collected from 83 adjuvant therapy-naive TNBC patients. These samples were used
      for global proteome profiling by iTRAQ-OFFGEL-LC-MS/MS approach in two series: a
      training cohort (n = 42) and a test set (n = 41). Patients who remains free of
      local or distant metastasis for a minimum of 5 years after surgery were
      classified in the no-relapse group; the others were in the relapse group. OPLS
      and Kaplan-Meier analyses were performed to select candidate markers, which were
      validated by immunohistochemistry. Three proteins were identified in the training
      set and validated in the test set by Kaplan-Meier method and immunohistochemistry
      (IHC): TrpRS as a good prognostic markers and DP and TSP1 as bad prognostic
      markers. We propose the establishment of an IHC test to calculate the score of
      TrpRS, DP, and TSP1 in TNBC tumors to evaluate the degree of aggressiveness of
      the tumors. Finally, we propose that DP and TSP1 could provide therapeutic
      targets for specific treatments. 

PMID- 26209612
TI  - Is estimated intra-operative blood loss a reliable predictor of surgical outcomes
      in laparoscopic colorectal cancer surgery?
AB  - BACKGROUND: Studies have shown that laparoscopic surgery for colorectal cancer is
      often associated with significantly reduced intra-operative blood loss compared
      to the corresponding open procedures. Increased intra-operative blood loss can be
      associated with increased risk of post-operative morbidity and mortality. We
      sought to determine whether estimated intra-operative blood loss was a reliable
      predictor of post-operative surgical outcomes. METHOD: Prospective data were
      collected for patients undergoing elective laparoscopic colorectal cancer
      resections from July 2011 to November 2013. Weighing swabs and measuring blood
      volume in suction devices calculated the estimated intra-operative blood loss.
      The operative outcome data including post-operative 30 day morbidity and
      mortality, length of hospital stay, re-admission and re-operation within 30 days
      were collected. The operative blood loss was grouped into Group 1 (less than 50
      ml, Group 2 (50-150 ml) and Group 3 (over 150 ml). Patients who underwent open
      operations and laparoscopic conversions were excluded. RESULTS: The median age,
      length of hospital stay, male to female ratio and body mass index were similar in
      the three groups. There was no 30-day mortality in any of the groups. The number
      of re-admissions within 30 days was similar in all groups. The re-operation rates
      within 30 days were higher in Groups 2 and 3 at 11% and 8.6%, respectively. The
      post-operative complications were 12.5%, 16.7%, and 26% in groups 1, 2 and 3,
      respectively. There were no anastomotic leaks requiring re-operation noted in
      Group 3. DISCUSSION: This study has shown that intra-operative blood loss was not
      associated with increased median length of stay nor did it increase the 30 day re
      admission rate. However, increased intra-operative blood loss was associated with
      increased incidence of post-operative morbidity and risk of reoperation within 30
      days.

PMID- 26209613
TI  - A survey of morbidity and mortality review meetings in the general surgical units
      of the West of Scotland.
AB  - BACKGROUND AND AIMS: There is little consensus as to the conduct of surgical
      morbidity and mortality review meetings. The aim of this survey was to determine
      how surgical morbidity and mortality meetings in the surgical units in the West
      of Scotland are carried out and to explore possible areas for improvement.
      METHODS AND RESULTS: Forty six surgical trainees distributed between the 15
      general surgery units of the West of Scotland were asked to provide details of
      their surgical morbidity and mortality meetings for the training year 2012-2013.
      Twenty-five of 46 (54%) specialty trainees responded with all units being
      represented. All had designated time for surgical morbidity and mortality review.
      Meeting frequency varied as follows: weekly (3 units), fortnightly (1 unit),
      monthly (10 units), three monthly (1 unit). Fewer than half the units (6)
      included Foundation Trainees, and only one meeting was attended by nursing staff.
      Five units had clear criteria for morbidity, but only three included morbidity
      collected from outpatient follow-up. A standardised proforma was used to present
      the cases in only 2 units. CONCLUSIONS: All 15 surgical units in the West of
      Scotland have a regular surgical morbidity and mortality meeting but significant
      variations were observed as to frequency and participating personnel. A more
      robust system for reporting morbidities should be considered.

PMID- 26209614
TI  - Laparoscopic colorectal surgery: Is it beneficial in the over 80s?
AB  - INTRODUCTION: Advanced age is often associated with higher incidence of co
      morbidities, advanced cancer and post-operative complications. The aim of this
      study was to compare the differences in pre-operative, co-morbidities, cancer
      stage and surgical outcome measures between patients over the age of 80 and those
      below 80 undergoing elective laparoscopic colorectal resection. METHOD: Data were
      analysed from a prospectively maintained database between February 2011 and June
      2012 and patients were subdivided into two groups (over 80 and under 80). All
      patients underwent laparoscopic colorectal surgery. Their length of stay, high
      dependency unit/intensive therapy unit stay, American Society of
      Anaesthesiologists grade, co-morbidities, conversion rates, Dukes' stage and post
      operative complication rates were compared. RESULTS: Of the 67 patients in the
      study, 57 were <80 at the time of surgery. Their American Society of
      Anaesthesiologists grade prior to surgery, as expected, was better than that of
      the >80 group, with 23% having an American Society of Anaesthesiologists grade of
      3 compared to 60% in the >80%. The prognosis of the patients in the two groups
      based on Dukes' stage was similar, with 63% of the <80 s having a good prognosis,
      compared to 80% in the >80 s. (Good prognosis = Dukes' A or B). The conversion
      rates were similar (26% of the <80 s compared to 20% of the > 80 s) Post
      operative length of stay was also similar in both groups (<80 s vs. >80 s: median
      5 vs. 5; p = 0.33). Post-operative complication rates were similar (17% of the
      <80 s vs. 20% of the >80 s). CONCLUSION: The short-term outcomes following
      laparoscopic colorectal surgery in the elderly are similar to that of younger
      patients. Laparoscopic surgery should therefore be offered to all patients
      irrespective of age.

PMID- 26209615
TI  - Transcriptional responses of Norway spruce (Picea abies) inner sapwood against
      Heterobasidion parviporum.
AB  - The white-rot fungus Heterobasidion parviporum Niemela & Korhonen establishes a
      necrotrophic interaction with Norway spruce (Picea abies (L.) H.Karst.) causing
      root and butt rot and growth losses in living trees. The interaction occurs first
      with the bark and the outer sapwood, as the pathogen enters the tree via wounds
      or root-to-root contacts. Later, when the fungus reaches the heartwood, it
      spreads therein creating a decay column, and the interaction mainly occurs in the
      inner sapwood where the tree creates a reaction zone. While bark and outer
      sapwood interactions are well studied, little is known about the nature of the
      transcriptional responses leading to the creation of a reaction zone. In this
      study, we sampled bark and sapwood both proximal and distal to the reaction zone
      in artificially inoculated and naturally infected trees. We quantified gene
      expression levels of candidate genes in secondary metabolite, hormone
      biosynthesis and signalling pathways using quantitative polymerase chain
      reaction. An up-regulation of mainly the phenylpropanoid pathway and jasmonic
      acid biosynthesis was found at the inoculation site, when inoculations were
      compared with wounding. We found that transcriptional responses in inner sapwood
      were similar to those reported upon infection through the bark. Our data suggest
      that the defence mechanism is induced due to direct fungal contact irrespective
      of the tissue type. Understanding the nature of these interactions is important
      when considering tree breeding-based resistance strategies to reduce the spread
      of the pathogen between and within trees. 

PMID- 26209616
TI  - Vegetation-zonation patterns across a temperate mountain cloud forest ecotone are
      not explained by variation in hydraulic functioning or water relations.
AB  - Many studies have demonstrated linkages between the occurrence of fog and
      ecophysiological functioning in cloud forests, but few have investigated
      hydraulic functioning as a determining factor that explains sharp changes in
      vegetation. The objective of this study was to compare the plant water status
      during cloud-immersed and non-immersed conditions and hydraulic vulnerability in
      branches and roots of species across a temperate, mountain fog ecotone. Because
      cloud forests are often dark, cool and very moist, we expected cloud forest
      species to have less drought-tolerant characteristics (i.e., lower Pe and P50-the
      pressures required to induce a 12 and 50% loss in hydraulic conductivity,
      respectively) relative to non-cloud forest species in adjacent (lower elevation)
      forests. Additionally, due to the ability of cloud forest species to absorb cloud
      fog water, we predicted greater improvements in hydraulic functioning during fog
      in cloud forest species relative to non-cloud forest species. Across the cloud
      forest ecotone, most species measured were very resistant to losses in
      conductivity with branch P50 values from -4.5 to -6.0 MPa, hydraulic safety
      margins (Psimin - P50) >1.5 MPa and low calculated hydraulic conductivity losses.
      Roots had greater vulnerabilities, with P50 values ranging from -1.4 to -2.5 MPa,
      leading to greater predicted losses in conductivity (~20%). Calculated values
      suggested strong losses of midday leaf hydraulic conductance in three of the four
      species, supporting the hydraulic segmentation hypothesis. In both cloud forest
      and hardwood species, Psis were greater on foggy days than sunny days,
      demonstrating the importance of fog periods to plant water balance across fog
      regimes. Thus, frequent fog did not result in systemic changes in hydraulic
      functioning or vulnerability to embolism across our temperate cloud forest
      ecotone. Finally, roots functioned with lower hydraulic conductivity than
      branches, suggesting that they may serve as more sensitive indicators of
      hydraulic functioning in these mesic, foggy ecosystems.

PMID- 26209617
TI  - Does reduced precipitation trigger physiological and morphological drought
      adaptations in European beech (Fagus sylvatica L.)? Comparing provenances across
      a precipitation gradient.
AB  - Global warming and associated decreases in summer rainfall may threaten tree
      vitality and forest productivity in many regions of the temperate zone in the
      future. One option for forestry to reduce the risk of failure is to plant
      genotypes which combine high productivity with drought tolerance. Growth
      experiments with provenances from different climates indicate that drought
      exposure can trigger adaptive drought responses in temperate trees, but it is not
      well known whether and to what extent regional precipitation reduction can
      increase the drought resistance of a species. We conducted a common garden growth
      experiment with five European beech (Fagus sylvatica L.) populations from a
      limited region with pronounced precipitation heterogeneity (816-544 mm year(-1)),
      where phylogenetically related provenances grew under small to large water
      deficits. We grew saplings of the five provenances at four soil moisture levels
      (dry to moist) and measured ~30 morphological (leaf and root properties, root :
      shoot ratio), physiological (leaf water status parameters, leaf conductance) and
      growth-related traits (above- and belowground productivity) with the aim to
      examine provenance differences in the drought response of morphological and
      physiological traits and to relate the responsiveness to precipitation at origin.
      Physiological traits were more strongly influenced by provenance (one-third of
      the studied traits), while structural traits were primarily affected by water
      availability in the experiment (two-thirds of the traits). The modulus of leaf
      tissue elasticity epsilon reached much higher values late in summer in plants
      from moist origins resulting in more rapid turgor loss and a higher risk of
      hydraulic failure upon drought. While experimental water shortage affected the
      majority of morphological and productivity-related traits in the five
      provenances, most parameters related to leaf water status were insensitive to
      water shortage. Thus, plant morphology, and root growth in particular, did
      respond to reduced water availability with higher phenotypic plasticity than did
      physiology. We conclude that beech provenances exposed to different precipitation
      regimes have developed some genotypic differences with respect to leaf water
      status regulation, but these adaptations are associated with only minor
      adaptation in plant morphology and they do not affect the growth rate of the
      saplings.

PMID- 26209618
TI  - Coordination of xylem hydraulics and stomatal regulation in keeping the integrity
      of xylem water transport in shoots of two compound-leaved tree species.
AB  - Hydraulic segmentation between proximal and distal organs has been hypothesized
      to be an important protective mechanism for plants to minimize the detrimental
      effects of drought-induced hydraulic failure. Uncertainties still exist regarding
      the degree of segmentation and the role of stomatal regulation in keeping
      hydraulic integrity of organs at different hierarchies. In the present study, we
      measured hydraulic conductivity and vulnerability in stems, compound leaf
      petioles and leaflet laminas of Fraxinus mandshurica Rupr. and Juglans
      mandshurica Maxim. growing in Changbai Mountain of Northeast China to identify
      the main locality where hydraulic segmentation occurs along the shoot water
      transport pathway. Stomatal conductance in response to leaf water potential
      change was also measured to investigate the role of stomatal regulation in
      avoiding extensive transpiration-induced embolism. No major contrasts were found
      between stems and compound leaf petioles in either hydraulic conductivity or
      vulnerability to drought-induced embolism, whereas a large difference in
      hydraulic vulnerability exists between compound leaf petioles and leaflet
      laminas. Furthermore, in contrast to the relatively large safety margins in stems
      (4.13 and 2.04 MPa) and compound leaf petioles (1.33 and 1.93 MPa), leaflet
      lamina hydraulic systems have substantially smaller or even negative safety
      margins (-0.17 and 0.47 MPa) in F. mandshurica and J. mandshurica. Under
      unstressed water conditions, gas exchange may be better optimized by allowing
      leaflet vascular system function with small safety margins. In the meantime,
      hydraulic safety of compound leaf petioles and stems are guaranteed by their
      large safety margins. In facing severe drought stress, larger safety margins in
      stems than in compound leaf petioles would allow plants to minimize the risk of
      catastrophic embolism in stems by sacrificing the whole compound leaves. A strong
      coordination between hydraulic and stomatal regulation appears to play a critical
      role in balancing the competing efficiency and safety requirements for xylem
      water transport and use in plants. 

PMID- 26209619
TI  - High rates of virus-induced gene silencing by tobacco rattle virus in Populus.
AB  - Virus-induced gene silencing (VIGS) has been shown to be an effective tool for
      investigating gene functions in herbaceous plant species, but has rarely been
      tested in trees. The establishment of a fast and reliable transformation system
      is especially important for woody plants, many of which are recalcitrant to
      transformation. In this study, we established a tobacco rattle virus (TRV)-based
      VIGS system for two Populus species, Populus euphratica and P. * canescens. Here,
      TRV constructs carrying a 266 bp or a 558 bp fragment of the phytoene desaturase
      (PDS) gene were Agrobacterium-infiltrated into leaves of the two poplar species.
      Agrobacterium-mediated delivery of the shorter insert, TRV2-PePDS266, into the
      host poplars resulted in expected photobleaching in both tree species, but not
      the longer insert, PePDS558. The efficiency of VIGS was temperature-dependent,
      increasing by raising the temperature from 18 to 28  degrees C. The optimized TRV
      VIGS system at 28  degrees C resulted in a high silencing frequency and
      efficiency up to 65-73 and 83-94%, respectively, in the two tested poplars.
      Moreover, syringe inoculation of Agrobacterium in 100 mM acetosyringone induced a
      more efficient silencing in the two poplar species, compared with other
      agroinfiltration methods, e.g., direct injection, misting and agrodrench. There
      were plant species-related differences in the response to VIGS because the
      photobleaching symptoms were more severe in P. * canescens than in P. euphratica.
      Furthermore, VIGS-treated P. euphratica exhibited a higher recovery rate (50%)
      after several weeks of the virus infection, compared with TRV-infected P. *
      canescens plants (20%). Expression stability of reference genes was screened to
      assess the relative abundance of PePDS mRNA in VIGS-treated P. euphratica and P.
      * canescens. PeACT7 was stably expressed in P. euphratica and UBQ-L was selected
      as the most suitable reference gene for P. * canescens using three different
      statistical approaches, geNorm, NormFinder and BestKeeper. Quantitative real-time
      PCR showed significant reductions in PDS transcripts (55-64%) in the
      photobleached leaves of both VIGS-treated poplar species. Our results demonstrate
      that the TRV-based VIGS provides a practical tool for gene functional analysis in
      Populus sp., especially in those poplar species which are otherwise recalcitrant
      to transformation.

PMID- 26209620
TI  - A Metalloproteinase Mirolysin of Tannerella forsythia Inhibits All Pathways of
      the Complement System.
AB  - Recent reports focusing on virulence factors of periodontal pathogens implicated
      proteinases as major determinants of remarkable pathogenicity of these species,
      with special emphasis on their capacity to modulate complement activity. In
      particular, bacteria-mediated cleavage of C5 and subsequent release of C5a seems
      to be an important phenomenon in the manipulation of the local inflammatory
      response in periodontitis. In this study, we present mirolysin, a novel
      metalloproteinase secreted by Tannerella forsythia, a well-recognized pathogen
      strongly associated with periodontitis. Mirolysin exhibited a strong effect on
      all complement pathways. It inhibited the classical and lectin complement
      pathways due to efficient degradation of mannose-binding lectin, ficolin-2,
      ficolin-3, and C4, whereas inhibition of the alternative pathway was caused by
      degradation of C5. This specificity toward complement largely resembled the
      activity of a previously characterized metalloproteinase of T. forsythia,
      karilysin. Interestingly, mirolysin released the biologically active C5a peptide
      in human plasma and induced migration of neutrophils. Importantly, we
      demonstrated that combination of mirolysin with karilysin, as well as a cysteine
      proteinase of another periodontal pathogen, Prevotella intermedia, resulted in a
      strong synergistic effect on complement. Furthermore, mutant strains of T.
      forsythia, devoid of either mirolysin or karilysin, showed diminished survival in
      human serum, providing further evidence for the synergistic inactivation of
      complement by these metalloproteinases. Taken together, our findings on
      interactions of mirolysin with complement significantly add to the understanding
      of immune evasion strategies of T. forsythia and expand the knowledge on
      molecular mechanisms driving pathogenic events in the infected periodontium.

PMID- 26209621
TI  - Langerhans Cells Suppress CD49a+ NK Cell-Mediated Skin Inflammation.
AB  - Recruitment of innate immune effector cells into sites of infection is a critical
      component of resistance to pathogen infection. Using a model of intradermal
      footpad injection of Candida albicans, we observed that inflammation as measured
      by footpad thickness and neutrophil recruitment occurred independent of adoptive
      immunity but was significantly reduced in MyD88(-/-) and IL-6(-/-) mice.
      Unexpectedly, huLangerin-DTA mice (DeltaLC) that lack Langerhans cells (LC)
      developed increased skin inflammation and expressed higher amounts of IL-6,
      suggesting a suppressive role for LC. Increased inflammation also occurred in
      Rag1(-/-) DeltaLC mice but was reversed by Ab-mediated ablation of NK cells.
      CXCR6(+)CD49a(+) NK cells are a liver-resident subset that can mediate
      inflammatory skin responses. We found that exaggerated skin inflammation was
      absent in DeltaLC * CXCR6(-/-) mice. Moreover, the exaggerated response in
      DeltaLC mice could be adoptively transferred with liver CD49a(+) NK cells.
      Finally, CD49a(+) NK cells in DeltaLC but not control mice were recruited to the
      skin, and inhibition of their recruitment prevented the exaggerated response.
      Thus, in the absence of LC, CD49a(+) liver NK cells display an inappropriately
      proinflammatory phenotype that results in increased local skin inflammation.
      These data reveal a novel function for LC in the regulation of this recently
      described subset of skin tropic NK cells.

PMID- 26209622
TI  - Reshaping of Human Macrophage Polarization through Modulation of Glucose
      Catabolic Pathways.
AB  - Macrophages integrate information from the tissue microenvironment and adjust
      their effector functions according to the prevalent extracellular stimuli.
      Therefore, macrophages can acquire a variety of activation (polarization) states,
      and this functional plasticity allows the adequate initiation, regulation, and
      resolution of inflammatory responses. Modulation of the glucose metabolism
      contributes to the macrophage adaptation to the surrounding cytokine milieu, as
      exemplified by the distinct glucose catabolism of macrophages exposed to LPS/IFN
      gamma or IL-4. To dissect the acquisition of macrophage effector functions in the
      absence of activating cytokines, we assessed the bioenergetic profile of
      macrophages generated in the presence of GM-CSF (GM-MO) or M-CSF (M-MO), which do
      not release pro- or anti-inflammatory cytokines unless subjected to additional
      activating stimuli. Compared to M-MO, GM-MO displayed higher oxygen consumption
      rate and aerobic glycolysis (extracellular acidification rate [ECAR]), as well as
      higher expression of genes encoding glycolytic enzymes. However, M-MO exhibited a
      significantly higher oxygen consumption rate/ECAR ratio. Surprisingly, whereas
      aerobic glycolysis positively regulated IL1B, TNF, and INHBA mRNA expression in
      both macrophage subtypes, mitochondrial respiration negatively affected IL6,
      IL1B, TNF, and CXCL10 mRNA expression in M-MO. The physiological significance of
      these results became evident under low oxygen tensions, as hypoxia enhanced ECAR
      in M-MO via HIF-1alpha and HIF-2alpha, increased expression of glycolytic enzymes
      and GM-MO-specific genes, and diminished expression of M-MO-associated genes.
      Therefore, our data indicate that GM-MO and M-MO display distinct bioenergetic
      profiles, and that hypoxia triggers a transcriptomic switch in macrophages by
      promoting a HIF-1alpha/HIF-2alpha-dependent increase in ECAR.

PMID- 26209623
TI  - Nucleotide-Induced Membrane-Proximal Proteolysis Controls the Substrate
      Specificity of T Cell Ecto-ADP-Ribosyltransferase ARTC2.2.
AB  - ARTC2.2 is a toxin-related, GPI-anchored ADP-ribosyltransferase expressed by
      murine T cells. In response to NAD(+) released from damaged cells during
      inflammation, ARTC2.2 ADP-ribosylates and thereby gates the P2X7 ion channel.
      This induces ectodomain shedding of metalloprotease-sensitive cell surface
      proteins. In this study, we show that ARTC2.2 itself is a target for P2X7
      triggered ectodomain shedding. We identify the metalloprotease cleavage site 3 aa
      upstream of the predicted GPI anchor attachment site of ARTC2.2. Intravenous
      injection of NAD(+) increased the level of enzymatically active ARTC2.2 in serum,
      indicating that this mechanism is operative also under inflammatory conditions in
      vivo. Radio-ADP-ribosylation assays reveal that shedding refocuses the target
      specificity of ARTC2.2 from membrane proteins to secretory proteins. Our results
      uncover nucleotide-induced membrane-proximal proteolysis as a regulatory
      mechanism to control the substrate specificity of ARTC2.2.

PMID- 26209624
TI  - Au-ACRAMTU-PEt3 Alters Redox Balance To Inhibit T Cell Proliferation and
      Function.
AB  - Although T cells play a critical role in protection from viruses, bacteria, and
      tumors, they also cause autoimmune diseases such as systemic lupus erythematosus,
      rheumatoid arthritis, and multiple sclerosis. Unwanted T cell responses during
      organ transplant, graft-versus-host disease, and allergies are also major
      clinical problems. Although drugs are available to suppress unwanted immune
      responses, they have limited efficacy with serious side effects. Thus, new
      therapeutics limiting T cell activation, proliferation, and function can make an
      immediate clinical impact. To identify new suppressors of lymphocyte activation,
      proliferation, and function, we examined the immunosuppressive activity of
      gold(I) analogs of platinum-acridine antitumor agents. We found that the gold
      complex Au-ACRAMTU-PEt3 is a potent suppressor of murine and human T cell
      activation. Preincubation with Au-ACRAMTU-PEt3 suppresses the proliferation of
      CD4(+) and CD8(+) T cells at a similar concentration as pharmaceutical grade
      cyclosporine A. Au-ACRAMTU-PEt3 pretreatment decreases the production of IFN
      gamma, TNF-alpha, IL-2, and IL-17 by human and murine CD4(+) and CD8(+) T cells.
      When mice were treated with Au-ACRAMTU-PEt3 during viral infection, the expansion
      of virus-specific CD8(+) T cells was decreased 10-fold and viral load was
      elevated. Taken together, these results demonstrate that Au-ACRAMTU-PEt3 has
      potent immunosuppressive activity that could be used to suppress immune responses
      during transplantation and autoimmunity.

PMID- 26209625
TI  - Genetic Interaction between Lyn, Ets1, and Btk in the Control of Antibody Levels.
AB  - Tight control of B cell differentiation into plasma cells (PCs) is critical for
      proper immune responses and the prevention of autoimmunity. The Ets1
      transcription factor acts in B cells to prevent PC differentiation. Ets1(-/-)
      mice accumulate PCs and produce autoantibodies. Ets1 expression is downregulated
      upon B cell activation through the BCR and TLRs and is maintained by the
      inhibitory signaling pathway mediated by Lyn, CD22 and SiglecG, and SHP-1. In the
      absence of these inhibitory components, Ets1 levels are reduced in B cells in a
      Btk-dependent manner. This leads to increased PCs, autoantibodies, and an
      autoimmune phenotype similar to that of Ets1(-/-) mice. Defects in inhibitory
      signaling molecules, including Lyn and Ets1, are associated with human lupus,
      although the effects are more subtle than the complete deficiency that occurs in
      knockout mice. In this study, we explore the effect of partial disruption of the
      Lyn/Ets1 pathway on B cell tolerance and find that Lyn(+/-)Ets1(+/-) mice
      demonstrate greater and earlier production of IgM, but not IgG, autoantibodies
      compared with Lyn(+/-) or Ets1(+/-) mice. We also show that Btk-dependent
      downregulation of Ets1 is important for normal PC homeostasis when inhibitory
      signaling is intact. Ets1 deficiency restores the decrease in steady state PCs
      and Ab levels observed in Btk(-/-) mice. Thus, depending on the balance of
      activating and inhibitory signals to Ets1, there is a continuum of effects on
      autoantibody production and PC maintenance. This ranges from full-blown
      autoimmunity with complete loss of Ets1-maintaining signals to reduced PC and Ab
      levels with impaired Ets1 downregulation.

PMID- 26209626
TI  - The TNF Family Molecules LIGHT and Lymphotoxin alphabeta Induce a Distinct
      Steroid-Resistant Inflammatory Phenotype in Human Lung Epithelial Cells.
AB  - Lung epithelial cells are considered important sources of inflammatory molecules
      and extracellular matrix proteins that contribute to diseases such as asthma.
      Understanding the factors that stimulate epithelial cells may lead to new
      insights into controlling lung inflammation. This study sought to investigate the
      responsiveness of human lung epithelial cells to the TNF family molecules LIGHT
      and lymphotoxin alphabeta (LTalphabeta). Bronchial and alveolar epithelial cell
      lines, and primary human bronchial epithelial cells, were stimulated with LIGHT
      and LTalphabeta, and expression of inflammatory cytokines and chemokines and
      markers of epithelial-mesenchymal transition and fibrosis/remodeling was
      measured. LTbeta receptor, the receptor shared by LIGHT and LTalphabeta, was
      constitutively expressed on all epithelial cells. Correspondingly, LIGHT and
      LTalphabeta strongly induced a limited but highly distinct set of inflammatory
      genes in all epithelial cells tested, namely the adhesion molecules ICAM-1 and
      VCAM-1; the chemokines CCL5, CCL20, CXCL1, CXCL3, CXCL5, and CXCL11; the
      cytokines IL-6, activin A and GM-CSF; and metalloproteinases matrix
      metalloproteinase-9 and a disintegrin and metalloproteinase domain-8.
      Importantly, induction of the majority of these inflammatory molecules was
      insensitive to the suppressive effects of the corticosteroid budesonide. LIGHT
      and LTalphabeta also moderately downregulated E-cadherin, a protein associated
      with maintaining epithelial integrity, but did not significantly drive production
      of extracellular matrix proteins or alpha-smooth muscle actin. Thus, LIGHT and
      LTalphabeta induce a distinct steroid-resistant inflammatory signature in airway
      epithelial cells via constitutively expressed LTbeta receptor. These findings
      support our prior murine studies that suggested the receptors for LIGHT and
      LTalphabeta contribute to development of lung inflammation characteristic of
      asthma and idiopathic pulmonary fibrosis.

PMID- 26209627
TI  - The T Cell Repertoire-Diversifying Enzyme TSSP Contributes to Thymic Selection of
      Diabetogenic CD4 T Cell Specificities Reactive to ChgA and IAPP Autoantigens.
AB  - Multiple studies highlighted the overtly self-reactive T cell repertoire in the
      diabetes-prone NOD mouse. This autoreactivity has primarily been linked to
      defects in apoptosis induction during central tolerance. Previous studies
      suggested that thymus-specific serine protease (TSSP), a putative serine protease
      expressed by cortical thymic epithelial cells and thymic dendritic cells, may
      edit the repertoire of self-peptides presented by MHC class II molecules and
      shapes the self-reactive CD4 T cell repertoire. To gain further insight into the
      role of TSSP in the selection of self-reactive CD4 T cells by endogenous self
      Ags, we examined the development of thymocytes expressing distinct diabetogenic
      TCRs sharing common specificity in a thymic environment lacking TSSP. Using mixed
      bone marrow chimeras, we evaluated the effect of TSSP deficiency confined to
      different thymic stromal cells on the differentiation of thymocytes expressing
      the chromogranin A-reactive BDC-2.5 and BDC-10.1 TCRs or the islet amyloid
      polypeptide-reactive TCR BDC-6.9 and BDC-5.2.9. We found that TSSP deficiency
      resulted in deficient positive selection and induced deletion of the BDC-6.9 and
      BDC-10.1 TCRs, but it did not affect the differentiation of the BDC-2.5 and BDC
      5.2.9 TCRs. Hence, TSSP has a subtle role in the generation of self-peptide
      ligands directing diabetogenic CD4 T cell development. These results provide
      additional evidence for TSSP activity as a novel mechanism promoting autoreactive
      CD4 T cell development/accumulation in the NOD mouse.

PMID- 26209628
TI  - Selective Targeting of a Disease-Related Conformational Isoform of Macrophage
      Migration Inhibitory Factor Ameliorates Inflammatory Conditions.
AB  - Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and
      counterregulator of glucocorticoids, is a potential therapeutic target. MIF is
      markedly different from other cytokines because it is constitutively expressed,
      stored in the cytoplasm, and present in the circulation of healthy subjects.
      Thus, the concept of targeting MIF for therapeutic intervention is challenging
      because of the need to neutralize a ubiquitous protein. In this article, we
      report that MIF occurs in two redox-dependent conformational isoforms. We show
      that one of the two isoforms of MIF, that is, oxidized MIF (oxMIF), is
      specifically recognized by three mAbs directed against MIF. Surprisingly, oxMIF
      is selectively expressed in the plasma and on the cell surface of immune cells of
      patients with different inflammatory diseases. In patients with acute infections
      or chronic inflammation, oxMIF expression correlated with inflammatory flare-ups.
      In addition, anti-oxMIF mAbs alleviated disease severity in mouse models of acute
      and chronic enterocolitis and improved, in synergy with glucocorticoids, renal
      function in a rat model of crescentic glomerulonephritis. We conclude that oxMIF
      represents the disease-related isoform of MIF; oxMIF is therefore a new
      diagnostic marker for inflammation and a relevant target for anti-inflammatory
      therapy.

PMID- 26209630
TI  - Laparoscopic Repair of Primary Inguinal Hernia Performed in Public Hospitals or
      Low-Volume Centers Have Increased Risk of Reoperation for Recurrence.
AB  - BACKGROUND: Inguinal hernia repair is traditionally carried out as either open or
      laparoscopic repair. Laparoscopic repair has been shown to be superior in terms
      of pain and discomfort, but has a higher risk of reoperation. Quality of inguinal
      hernia repair is related to factors such as method of repair, characteristics of
      patients, and possibly the annual volume of procedures performed by a center. The
      aim of this study was to test the hypothesis that hospital volume and type of
      hospital (private vs public) could influence the reoperation rate for recurrence
      as a marker of surgical quality of care. METHODS: This study was based on data
      from the Danish Hernia Database covering the period from January 1, 1998, to
      December 31, 2013. Hernia repairs included in this study were laparoscopic repair
      of primary, inguinal hernias in the elective setting, performed on adult male
      patients. RESULTS: A total of 14 532 laparoscopic repairs were included for
      analysis. Centers reporting less than 50 procedures a year had a significantly
      higher cumulative reoperation rate compared with centers reporting more than 50
      procedures a year (9.97% vs 6.06%), P < .0001. Private centers had a lower
      cumulative reoperation rate compared with public centers: 5.36% versus 8.53%, P
      <= .0001. Type of center and center volume were both independent risk factors for
      reoperation in a Cox regression model. CONCLUSION: Hospital volume had an effect
      on the reoperation rate for recurrence after laparoscopic inguinal hernia repair.
      Furthermore, private centers performed better than public centers irrespective of
      volume.

PMID- 26209629
TI  - CXCR3 Polymorphism and Expression Associate with Spontaneous Preterm Birth.
AB  - Spontaneous preterm birth (SPTB) is a major factor associating with deaths and
      with lowered quality of life in humans. Environmental and genetic factors
      influence the susceptibility. Previously, by analyzing families with recurrent
      SPTB in linkage analysis, we identified a linkage peak close to the gene encoding
      CXCR3. Present objectives were to investigate the association of CXCR3 with SPTB
      in Finnish mothers (n = 443) and infants (n = 747), to analyze CXCR3 expression
      levels in human placenta and levels of its ligands in umbilical cord blood, and
      to verify the influence of Cxcr3 on SPTB-associating cytokines in mice. We
      detected an association between an intronic CXCR3 polymorphism, rs2280964, and
      SPTB in infants from families with recurrent preterm births (p = 0.009 versus
      term controls, odds ratio 0.52, 95% confidence interval 0.32-0.86). The minor
      allele was protective and undertransmitted to SPTB infants (p = 0.007). In the
      placenta and fetal membranes, the rs2280964 major allele homozygotes had higher
      expression levels than minor allele homozygotes; decidual trophoblasts showed
      strong CXCR3 immunoreactivity. Expression was higher in SPTB placentas compared
      with those from elective deliveries. Concentration of a CXCR3 ligand, CXCL9, was
      increased in cord blood from SPTB, and the protective rs2280964 allele was
      associated with low CXCL9. In CXCR3-deficient mice (Mus musculus), SPTB
      associating cytokines were not acutely increased in amniotic fluid after preterm
      birth-inducing dose of maternal LPS. Our results indicate that CXCR3 contributes
      to SPTB. Activation of CXCR3 signaling may disturb the maternal-fetal tolerance,
      and this may promote labor.

PMID- 26209631
TI  - Fatal air embolism during endoscopic retrograde cholangiopancreatography (ERCP):
      An 'impossible' diagnosis for the forensic pathologist.
AB  - Fatal air embolism related to endoscopic retrograde cholangiopancreatography is a
      very rare phenomenon. The authors describe the case of a 51-year-old female
      patient who developed this mortal complication; a computed tomography (CT)
      examination was performed in articulo mortis by the physicians. Autopsy was
      unreliable because of bizarre post-mortem changes (reabsorption of intra-cardiac
      gas vs. conservation of intra-cranial gas) and a lack of strong diagnostic value
      of histological findings. The right diagnosis was possible thanks only to the CT
      examination that permitted the assumption of this possible cause of death before
      the autopsy and to prepare the necessary procedures to recognise and probe air
      embolism. This case exemplifies how early post-mortem imaging can be crucial to
      avoid a wrong diagnosis. 

PMID- 26209632
TI  - Estimation of height from the length of the sternum in an adult Indian
      population.
AB  - Stature estimation is one of the essential early steps during forensic
      investigation of human skeletal remains. The aim of the present study was to
      obtain a linear regression formula for estimating stature from sternal length of
      a central Indian population. The study includes 92 male cadavers brought for
      medico-legal autopsies. The linear regression equations were derived from
      manubrium, mesosternum and the total sternal length. The regression model
      provided a 95% confidence interval of +/-14.8 cm and a correlation coefficient of
      0.55. Compared with other studies, regression formulae based on the length of the
      sternum provided considerably larger standard errors than that based on long bone
      lengths. The study indicates that sternal length in relation with body stature
      shows a moderate positive correlation and relatively low reliability in
      estimating stature, and has limited forensic value. 

PMID- 26209633
TI  - Kv4.2 and accessory dipeptidyl peptidase-like protein 10 (DPP10) subunit
      preferentially form a 4:2 (Kv4.2:DPP10) channel complex.
AB  - Kv4 is a member of the voltage-gated K(+) channel family and forms a complex with
      various accessory subunits. Dipeptidyl aminopeptidase-like protein (DPP) is one
      of the auxiliary subunits for the Kv4 channel. Although DPP has been well
      characterized and is known to increase the current amplitude and accelerate the
      inactivation and recovery from inactivation of Kv4 current, it remains to be
      determined how many DPPs bind to one Kv4 channel. To examine whether the
      expression level of DPP changes the biophysical properties of Kv4, we expressed
      Kv4.2 and DPP10 in different ratios in Xenopus oocytes and analyzed the currents
      under two-electrode voltage clamp. The current amplitude and the speed of
      recovery from inactivation of Kv4.2 changed depending on the co-expression level
      of DPP10. This raised the possibility that the stoichiometry of the Kv4.2-DPP10
      complex is variable and affects the biophysical properties of Kv4.2. We next
      determined the stoichiometry of DPP10 alone by subunit counting using single
      molecule imaging. Approximately 70% of the DPP10 formed dimers in the plasma
      membrane, and the rest existed as monomers in the absence of Kv4.2. We next
      determined the stoichiometry of the Kv4.2-DPP10 complex; Kv4.2-mCherry and mEGFP
      DPP10 were co-expressed in different ratios and the stoichiometries of Kv4.2
      DPP10 complexes were evaluated by the subunit counting method. The stoichiometry
      of the Kv4.2-DPP10 complex was variable depending on the relative expression
      level of each subunit, with a preference for 4:2 stoichiometry. This preference
      may come from the bulky dimeric structure of the extracellular domain of DPP10. 

PMID- 26209634
TI  - Small GTPase Rab2B and Its Specific Binding Protein Golgi-associated Rab2B
      Interactor-like 4 (GARI-L4) Regulate Golgi Morphology.
AB  - Rab small GTPases are crucial regulators of the membrane traffic that maintains
      organelle identity and morphology. Several Rab isoforms are present in the Golgi,
      and it has been suggested that they regulate the compacted morphology of the
      Golgi in mammalian cells. However, the functional relationships among the Golgi
      resident Rabs, e.g. whether they are functionally redundant or different, are
      poorly understood. In this study, we used specific siRNAs to perform genome-wide
      screening for human Rabs that are involved in Golgi morphology in HeLa-S3 cells.
      The results showed that knockdown of any one of the six Rab isoforms
      (Rab1A/1B/2A/2B/6B/8A) induced fragmentation of the Golgi in HeLa-S3 cells and
      that its phenotype was rescued by re-expression of their respective siRNA
      resistant construct. We then performed systematic knockdown-rescue experiments in
      relation to each of the six Rabs. Interestingly, with the exception of the Rab8A
      knockdown, the Golgi fragmentation phenotype induced by knockdown of a single Rab
      isoform, e.g. Rab2B, was efficiently rescued by re-expression of its siRNA
      resistant Rab alone, not by any of the other five Rabs, e.g. Rab2A, which is
      highly homologous to Rab2B, indicating that these Rab isoforms non-redundantly
      regulate Golgi morphology possibly through interaction with isoform-specific
      effector molecules. In addition, we identified Golgi-associated Rab2B interactor
      like 4 (GARI-L4) as a novel Golgi-resident Rab2B-specific binding protein whose
      knockdown also induced fragmentation of the Golgi. Our findings suggest that the
      compacted Golgi morphology of mammalian cells is finely tuned by multiple sets of
      Rab (or Rab-effector complexes) that for the most part function independently. 

PMID- 26209635
TI  - NMR studies demonstrate a unique AAB composition and chain register for a
      heterotrimeric type IV collagen model peptide containing a natural interruption
      site.
AB  - All non-fibrillar collagens contain interruptions in the (Gly-X-Y)n repeating
      sequence, such as the more than 20 interruptions found in chains of basement
      membrane type IV collagen. Two selectively doubly labeled peptides are designed
      to model a site in type IV collagen with a GVG interruption in the alpha1(IV) and
      a corresponding GISLK sequence within the alpha2(IV) chain. CD and NMR studies on
      a 2:1 mixture of these two peptides support the formation of a single-component
      heterotrimer that maintains the one-residue staggering in the triple-helix, has a
      unique chain register, and contains hydrogen bonds at the interruption site.
      Formation of hydrogen bonds at interruption sites may provide a driving force for
      self-assembly and chain register in type IV and other non-fibrillar collagens.
      This study illustrates the potential role of interruptions in the structure,
      dynamics, and folding of natural collagen heterotrimers and forms a basis for
      understanding their biological role. 

PMID- 26209636
TI  - Hexapeptides that inhibit processing of branched DNA structures induce a dynamic
      ensemble of Holliday junction conformations.
AB  - Holliday junctions are critical intermediates in DNA recombination, repair, and
      restart of blocked replication. Hexapeptides have been identified that bind to
      junctions and inhibit various junction-processing enzymes, and these peptides
      confer anti-microbial and anti-tumor properties. Earlier studies suggested that
      inhibition results from stabilization of peptide-bound Holliday junctions in the
      square planar conformation. Here, we use single molecule fluorescence resonance
      energy transfer (smFRET) and two model junctions, which are AT- or GC-rich at the
      branch points, to show that binding of the peptide KWWCRW induces a dynamic
      ensemble of junction conformations that differs from both the square planar and
      stacked X conformations. The specific features of the conformational
      distributions differ for the two peptide-bound junctions, but both junctions
      display greatly decreased Mg(2+) dependence and increased conformational
      fluctuations. The smFRET results, complemented by gel mobility shift and small
      angle x-ray scattering analyses, reveal structural effects of peptides and
      highlight the sensitivity of smFRET for analyzing complex mixtures of DNA
      structures. The peptide-induced conformational dynamics suggest multiple stacking
      arrangements of aromatic amino acids with the nucleobases at the junction core.
      This conformational heterogeneity may inhibit DNA processing by increasing the
      population of inactive junction conformations, thereby preventing the binding of
      processing enzymes and/or resulting in their premature dissociation. 

PMID- 26209638
TI  - Structural insights into the affinity of Cel7A carbohydrate-binding module for
      lignin.
AB  - The high cost of hydrolytic enzymes impedes the commercial production of
      lignocellulosic biofuels. High enzyme loadings are required in part due to their
      non-productive adsorption to lignin, a major component of biomass. Despite
      numerous studies documenting cellulase adsorption to lignin, few attempts have
      been made to engineer enzymes to reduce lignin binding. In this work, we used
      alanine-scanning mutagenesis to elucidate the structural basis for the lignin
      affinity of Trichoderma reesei Cel7A carbohydrate binding module (CBM). T. reesei
      Cel7A CBM mutants were produced with a Talaromyces emersonii Cel7A catalytic
      domain and screened for their binding to cellulose and lignin. Mutation of
      aromatic and polar residues on the planar face of the CBM greatly decreased
      binding to both cellulose and lignin, supporting the hypothesis that the
      cellulose-binding face is also responsible for lignin affinity. Cellulose and
      lignin affinity of the 31 mutants were highly correlated, although several
      mutants displayed selective reductions in lignin or cellulose affinity. Four
      mutants with increased cellulose selectivity (Q2A, H4A, V18A, and P30A) did not
      exhibit improved hydrolysis of cellulose in the presence of lignin. Further
      reduction in lignin affinity while maintaining a high level of cellulose affinity
      is thus necessary to generate an enzyme with improved hydrolysis capability. This
      work provides insights into the structural underpinnings of lignin affinity,
      identifies residues amenable to mutation without compromising cellulose affinity,
      and informs engineering strategies for family one CBMs. 

PMID- 26209637
TI  - Hyaluronan and Its Heavy Chain Modification in Asthma Severity and Experimental
      Asthma Exacerbation.
AB  - Hyaluronan (HA) is a large (>1500 kDa) polysaccharide of the extracellular matrix
      that has been linked to severity and inflammation in asthma. During inflammation,
      HA becomes covalently modified with heavy chains (HC-HA) from inter-alpha
      inhibitor (IalphaI), which functions to increase its avidity for leukocytes. Our
      murine model of allergic pulmonary inflammation suggested that HC-HA may
      contribute to inflammation, adversely effecting lower airway remodeling and
      asthma severity. Our objective was to characterize the levels of HA and HC-HA in
      asthmatic subjects and to correlate these levels with asthma severity. We
      determined the levels and distribution of HA and HC-HA (i) from asthmatic and
      control lung tissue, (ii) in bronchoalveolar lavage fluid obtained from non
      severe and severe asthmatics and controls, and (iii) in serum and urine from
      atopic asthmatics after an experimental asthma exacerbation. HC-HA distribution
      was observed (i) in the thickened basement membrane of asthmatic lower airways,
      (ii) around smooth muscle cells of the asthmatic submucosa, and (iii) around
      reserve cells of the asthmatic epithelium. Patients with severe asthma had
      increased HA levels in bronchoalveolar lavage fluid that correlated with
      pulmonary function and nitric oxide levels, whereas HC-HA was only observed in a
      patient with non-severe asthma. After an experimental asthma exacerbation, serum
      HA was increased within 4 h after challenge and remained elevated through 5 days
      after challenge. Urine HA and HC-HA were not significantly different. These data
      implicate HA and HC-HA in the pathogenesis of asthma severity that may occur in
      part due to repetitive asthma exacerbations over the course of the disease. 

PMID- 26209639
TI  - Interleukin-1 Receptor Type 2 Acts with c-Fos to Enhance the Expression of
      Interleukin-6 and Vascular Endothelial Growth Factor A in Colon Cancer Cells and
      Induce Angiogenesis.
AB  - Interleukin-1 receptor type 2 (IL1R2) acts as a decoy receptor of exogenous IL-1;
      however, its intracellular activity is poorly understood. We previously
      demonstrated that IL1R2 intracellularly activates the expression of several
      proinflammatory cytokines and affects cell migration. In this study, we found
      that intracellular IL1R2 expression was increased in human colorectal cancer
      cells (CRCs) compared with normal colon cells. We also observed that the mRNA
      levels of IL1R2 were highly correlated with IL-6 in tumor tissues of CRC
      patients. By modulating its expression in CRC cells, we verified that enhanced
      IL1R2 expression transcriptionally activated the expression of IL-6 and VEGF-A.
      Conditioned medium harvested from IL1R2-overexpressing CRC cells contained higher
      levels of IL-6 and VEGF-A than that from vector control cells and significantly
      enhanced the proliferation, migration, and tube formation of cultured endothelial
      cells. We further demonstrated a positive association of intracellular IL1R2
      levels with tumor growth and microvessel density in xenograft mouse models. These
      results revealed that IL1R2 activates the expression of angiogenic factors.
      Mechanistically, we revealed that IL1R2 complexes with c-Fos and binds to the AP
      1 site at the IL-6 and VEGF-A promoters. Together, these results reveal a novel
      function of intracellular IL1R2 that acts with c-Fos to enhance the transcription
      of IL-6 and VEGF-A, which promotes angiogenesis in CRC. 

PMID- 26209641
TI  - Reply to the letter to the editor 'Journey to a faraway land' by Alkan et al.

PMID- 26209640
TI  - In pursuit of genes of glucose metabolism.

PMID- 26209642
TI  - Value of KRAS as prognostic or predictive marker in NSCLC: results from the
      TAILOR trial.
AB  - BACKGROUND: The prognostic and predictive role of KRAS mutations in advanced
      nonsmall-cell lung cancer (NSCLC) is still unclear. TAILOR prospectively assessed
      the prognostic and predictive value of KRAS mutations in NSCLC patients treated
      with erlotinib or docetaxel in second line. PATIENTS AND METHODS: NSCLC patients
      from 52 Italian hospitals were genotyped for KRAS and EGFR mutational status in
      two independent laboratories. Wild-type EGFR patients (N = 218) received first
      line platinum-based chemotherapy and were randomly allocated at progression to
      erlotinib or docetaxel. Overall survival (OS) according to KRAS mutational status
      was the primary end point. RESULTS: KRAS mutations were present in 23% of TAILOR
      randomized cases. The presence of a KRAS mutation did not adversely affect
      progression-free (PFS) or overall (OS) survival [hazard ratio (HR) PFS = 1.01,
      95% confidence interval (CI) 0.71-1.41, P = 0.977; OS = 1.24, 95% CI 0.87-1.77, P
      = 0.233], nor influenced treatment outcome (test for interaction: OS P = 0.965;
      PFS P = 0.417). Patients randomized to docetaxel treatment experienced longer
      survival independently from the KRAS mutational status of their tumors (HR:
      mutated KRAS 0.81, 95% CI 0.45-1.47; wild-type KRAS 0.79, 95% CI 0.57-1.10).
      CONCLUSION: In TAILOR, KRAS was neither prognostic nor predictive of benefit for
      either docetaxel or erlotinib. Docetaxel remains superior independently from KRAS
      status for second-line treatment in EGFR wild-type advanced NSCLC patients.
      CLINICAL TRIAL REGISTRATION: NCT00637910.

PMID- 26209644
TI  - Control of tissue growth by Yap relies on cell density and F-actin in zebrafish
      fin regeneration.
AB  - Caudal fin regeneration is characterized by a proliferation boost in the
      mesenchymal blastema that is controlled precisely in time and space. This allows
      a gradual and robust restoration of original fin size. However, how this is
      established and regulated is not well understood. Here, we report that Yap, the
      Hippo pathway effector, is a chief player in this process: functionally
      manipulating Yap during regeneration dramatically affects cell proliferation and
      expression of key signaling pathways, impacting regenerative growth. The
      intracellular location of Yap is tightly associated with different cell densities
      along the blastema proximal-distal axis, which correlate with alterations in cell
      morphology, cytoskeleton and cell-cell contacts in a gradient-like manner.
      Importantly, Yap inactivation occurs in high cell density areas, conditional to F
      actin distribution and polymerization. We propose that Yap is essential for fin
      regeneration and that its function is dependent on mechanical tension, conferred
      by a balancing act of cell density and cytoskeleton activity. 

PMID- 26209643
TI  - Neurog1 can partially substitute for Atoh1 function in hair cell differentiation
      and maintenance during organ of Corti development.
AB  - Atoh1, a basic helix-loop-helix (bHLH) transcription factor (TF), is essential
      for the differentiation of hair cells (HCs), mechanotransducers that convert
      sound into auditory signals in the mammalian organ of Corti (OC). Previous work
      demonstrated that replacing mouse Atoh1 with the fly ortholog atonal rescues HC
      differentiation, indicating functional replacement by other bHLH genes. However,
      replacing Atoh1 with Neurog1 resulted in reduced HC differentiation compared with
      transient Atoh1 expression in a 'self-terminating' Atoh1 conditional null mouse
      (Atoh1-Cre; Atoh1(f/f)). We now show that combining Neurog1 in one allele with
      removal of floxed Atoh1 in a self-terminating conditional mutant (Atoh1-Cre;
      Atoh1(f/kiNeurog1)) mouse results in significantly more differentiated inner HCs
      and outer HCs that have a prolonged longevity of 9 months compared with Atoh1
      self-terminating littermates. Stereocilia bundles are partially disorganized,
      disoriented and not HC type specific. Replacement of Atoh1 with Neurog1 maintains
      limited expression of Pou4f3 and Barhl1 and rescues HCs quantitatively, but not
      qualitatively. OC patterning and supporting cell differentiation are also
      partially disrupted. Diffusible factors involved in patterning are reduced (Fgf8)
      and factors involved in cell-cell interactions are affected (Jag1, Hes5). Despite
      the presence of many HCs with stereocilia these mice are deaf, possibly owing to
      HC and OC patterning defects. This study provides a novel approach to disrupt OC
      development through modulating the HC-specific intracellular TF network. The
      resulting disorganized OC indicates that normally differentiated HCs act as 'self
      organizers' for OC development and that Atoh1 plays a crucial role to initiate HC
      stereocilia differentiation independently of HC viability. 

PMID- 26209645
TI  - Fat1 interacts with Fat4 to regulate neural tube closure, neural progenitor
      proliferation and apical constriction during mouse brain development.
AB  - Mammalian brain development requires coordination between neural precursor
      proliferation, differentiation and cellular organization to create the intricate
      neuronal networks of the adult brain. Here, we examined the role of the atypical
      cadherins Fat1 and Fat4 in this process. We show that mutation of Fat1 in mouse
      embryos causes defects in cranial neural tube closure, accompanied by an increase
      in the proliferation of cortical precursors and altered apical junctions, with
      perturbations in apical constriction and actin accumulation. Similarly, knockdown
      of Fat1 in cortical precursors by in utero electroporation leads to
      overproliferation of radial glial precursors. Fat1 interacts genetically with the
      related cadherin Fat4 to regulate these processes. Proteomic analysis reveals
      that Fat1 and Fat4 bind different sets of actin-regulating and junctional
      proteins. In vitro data suggest that Fat1 and Fat4 form cis-heterodimers,
      providing a mechanism for bringing together their diverse interactors. We propose
      a model in which Fat1 and Fat4 binding coordinates distinct pathways at apical
      junctions to regulate neural progenitor proliferation, neural tube closure and
      apical constriction. 

PMID- 26209647
TI  - Transcriptome of human foetal heart compared with cardiomyocytes from pluripotent
      stem cells.
AB  - Differentiated derivatives of human pluripotent stem cells (hPSCs) are often
      considered immature because they resemble foetal cells more than adult, with hPSC
      derived cardiomyocytes (hPSC-CMs) being no exception. Many functional features of
      these cardiomyocytes, such as their cell morphology, electrophysiological
      characteristics, sarcomere organization and contraction force, are underdeveloped
      compared with adult cardiomyocytes. However, relatively little is known about how
      their gene expression profiles compare with the human foetal heart, in part
      because of the paucity of data on the human foetal heart at different stages of
      development. Here, we collected samples of matched ventricles and atria from
      human foetuses during the first and second trimester of development. This
      presented a rare opportunity to perform gene expression analysis on the
      individual chambers of the heart at various stages of development, allowing us to
      identify not only genes involved in the formation of the heart, but also specific
      genes upregulated in each of the four chambers and at different stages of
      development. The data showed that hPSC-CMs had a gene expression profile similar
      to first trimester foetal heart, but after culture in conditions shown previously
      to induce maturation, they cluster closer to the second trimester foetal heart
      samples. In summary, we demonstrate how the gene expression profiles of human
      foetal heart samples can be used for benchmarking hPSC-CMs and also contribute to
      determining their equivalent stage of development. 

PMID- 26209646
TI  - Yap and Taz regulate retinal pigment epithelial cell fate.
AB  - The optic vesicle comprises a pool of bi-potential progenitor cells from which
      the retinal pigment epithelium (RPE) and neural retina fates segregate during
      ocular morphogenesis. Several transcription factors and signaling pathways have
      been shown to be important for RPE maintenance and differentiation, but an
      understanding of the initial fate specification and determination of this ocular
      cell type is lacking. We show that Yap/Taz-Tead activity is necessary and
      sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A
      Tead-responsive transgene is expressed within the domain of the optic cup from
      which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective
      RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma.
      Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant
      alleles such that, when Yap and Taz are both absent, optic vesicle progenitor
      cells completely lose their ability to form RPE. The mechanism of Yap-dependent
      RPE cell type determination is reliant on both nuclear localization of Yap and
      interaction with a Tead co-factor. In contrast to loss of Yap and Taz,
      overexpression of either protein within optic vesicle progenitors leads to
      ectopic pigmentation in a dosage-dependent manner. Overall, this study identifies
      Yap and Taz as key early regulators of RPE genesis and provides a mechanistic
      framework for understanding the congenital ocular defects of Sveinsson's
      chorioretinal atrophy and congenital retinal coloboma. 

PMID- 26209648
TI  - A transgenic quail model that enables dynamic imaging of amniote embryogenesis.
AB  - Embryogenesis is the coordinated assembly of tissues during morphogenesis through
      changes in individual cell behaviors and collective cell movements. Dynamic
      imaging, combined with quantitative analysis, is ideal for investigating
      fundamental questions in developmental biology involving cellular
      differentiation, growth control and morphogenesis. However, a reliable amniote
      model system that is amenable to the rigors of extended, high-resolution imaging
      and cell tracking has been lacking. To address this shortcoming, we produced a
      novel transgenic quail that ubiquitously expresses nuclear localized monomer
      cherry fluorescent protein (chFP). We characterize the expression pattern of chFP
      and provide concrete examples of how Tg(PGK1:H2B-chFP) quail can be used to
      dynamically image and analyze key morphogenetic events during embryonic stages X
      to 11. 

PMID- 26209649
TI  - Multiple cell and population-level interactions with mouse embryonic stem cell
      heterogeneity.
AB  - Much of development and disease concerns the generation of gene expression
      differences between related cells sharing similar niches. However, most analyses
      of gene expression only assess population and time-averaged levels of steady
      state transcription. The mechanisms driving differentiation are buried within
      snapshots of the average cell, lacking dynamic information and the diverse
      regulatory history experienced by individual cells. Here, we use a quantitative
      imaging platform with large time series data sets to determine the regulation of
      developmental gene expression by cell cycle, lineage, motility and environment.
      We apply this technology to the regulation of the pluripotency gene Nanog in
      mouse embryonic stem cells. Our data reveal the diversity of cell and population
      level interactions with Nanog dynamics and heterogeneity, and how this regulation
      responds to triggers of pluripotency. Cell cycles are highly heterogeneous and
      cycle time increases with Nanog reporter expression, with longer, more variable
      cycle times as cells approach ground-state pluripotency. Nanog reporter
      expression is highly stable over multiple cell generations, with fluctuations
      within cycles confined by an attractor state. Modelling reveals an environmental
      component to expression stability, in addition to any cell-autonomous behaviour,
      and we identify interactions of cell density with both cycle behaviour and Nanog.
      Rex1 expression dynamics showed shared and distinct regulatory effects. Overall,
      our observations of multiple partially overlapping dynamic heterogeneities imply
      complex cell and environmental regulation of pluripotent cell behaviour, and
      suggest simple deterministic views of stem cell states are inappropriate. 

PMID- 26209651
TI  - A biological rationale for musical consonance.
AB  - The basis of musical consonance has been debated for centuries without
      resolution. Three interpretations have been considered: (i) that consonance
      derives from the mathematical simplicity of small integer ratios; (ii) that
      consonance derives from the physical absence of interference between harmonic
      spectra; and (iii) that consonance derives from the advantages of recognizing
      biological vocalization and human vocalization in particular. Whereas the
      mathematical and physical explanations are at odds with the evidence that has now
      accumulated, biology provides a plausible explanation for this central issue in
      music and audition. 

PMID- 26209652
TI  - Alexander Dalgarno: From atomic and molecular physics to astronomy and aeronomy.

PMID- 26209650
TI  - Key mediators of somatic ATR signaling localize to unpaired chromosomes in
      spermatocytes.
AB  - Meiotic silencing of unpaired chromatin (MSUC) occurs during the first meiotic
      prophase, as chromosomes that fail to pair are sequestered into a
      transcriptionally repressive nuclear domain. This phenomenon is exemplified by
      the heterologous sex chromosomes of male mammals, where the ATR DNA damage
      response kinase is crucial for this silencing event. However, the mechanisms
      underlying the initiation of MSUC remain unknown. Here, we show that essential
      components of ATR signaling in murine somatic cells are spatially confined to
      unpaired chromosomes in spermatocytes, including the ATR-dependent
      phosphorylation of the single-stranded DNA (ssDNA)-binding complex replication
      protein A (RPA) and the checkpoint kinase CHK1. These observations support a
      model in which ssDNA plays a central role in the recruitment of ATR during MSUC,
      and provide a link to meiotic progression through activation of CHK1. 

PMID- 26209653
TI  - Daniel Steinberg, 1922-2015.

PMID- 26209654
TI  - Local axonal protection by WldS as revealed by conditional regulation of protein
      stability.
AB  - The expression of the mutant Wallerian degeneration slow (WldS) protein
      significantly delays axonal degeneration from various nerve injuries and in
      multiple species; however, the mechanism for its axonal protective property
      remains unclear. Although WldS is localized predominantly in the nucleus, it also
      is present in a smaller axonal pool, leading to conflicting models to account for
      the WldS fraction necessary for axonal protection. To identify where WldS
      activity is required to delay axonal degeneration, we adopted a method to alter
      the temporal expression of WldS protein in neurons by chemically regulating its
      protein stability. We demonstrate that continuous WldS activity in the axonal
      compartment is both necessary and sufficient to delay axonal degeneration.
      Furthermore, by specifically increasing axonal WldS expression postaxotomy, we
      reveal a critical period of 4-5 h postinjury during which the course of Wallerian
      axonal degeneration can be halted. Finally, we show that NAD(+), the metabolite
      of WldS/nicotinamide mononucleotide adenylyltransferase enzymatic activity, is
      sufficient and specific to confer WldS-like axon protection and is a likely
      molecular mediator of WldS axon protection. The results delineate a therapeutic
      window in which the course of Wallerian degeneration can be delayed even after
      injures have occurred and help narrow the molecular targets of WldS activity to
      events within the axonal compartment. 

PMID- 26209655
TI  - Reply to Peters et al.: Proton transfers are plausible initiation and termination
      steps on Cr(III) sites in ethylene polymerization.

PMID- 26209656
TI  - Reexamining the evidence for proton transfers in ethylene polymerization.

PMID- 26209657
TI  - Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase:
      implications for autoimmunity in rheumatoid arthritis.
AB  - BACKGROUND: Periodontitis (PD) is a known risk factor for rheumatoid arthritis
      (RA) and there is increasing evidence that the link between the two diseases is
      due to citrullination by the unique bacterial peptidylarginine deiminase (PAD)
      enzyme expressed by periodontal pathogen Pophyromonas gingivalis (PPAD). However,
      the precise mechanism by which PPAD could generate potentially immunogenic
      peptides has remained controversial due to lack of information about the
      structural and catalytic mechanisms of the enzyme. OBJECTIVES: By solving the 3D
      structure of PPAD we aim to characterise activity and elucidate potential
      mechanisms involved in breach of tolerance to citrullinated proteins in RA.
      METHODS: PPAD and a catalytically inactive mutant PPAD(C351A) were crystallised
      and their 3D structures solved. Key residues identified from 3D structures were
      examined by mutations. Fibrinogen and alpha-enolase were incubated with PPAD and
      P. gingivalis arginine gingipain (RgpB) and citrullinated peptides formed were
      sequenced and quantified by mass spectrometry. RESULTS: Here, we solve the
      crystal structure of a truncated, highly active form of PPAD. We confirm
      catalysis is mediated by the following residues: Asp130, His236, Asp238, Asn297
      and Cys351 and show Arg152 and Arg154 may determine the substrate specificity of
      PPAD for C-terminal arginines. We demonstrate the formation of 37 C-terminally
      citrullinated peptides from fibrinogen and 11 from alpha-enolase following
      incubation with tPPAD and RgpB. CONCLUSIONS: PPAD displays an unequivocal
      specificity for C-terminal arginine residues and readily citrullinates peptides
      from key RA autoantigens. The formation of these novel citrullinated peptides may
      be involved in breach of tolerance to citrullinated proteins in RA.

PMID- 26209659
TI  - Low urinary indoxyl sulfate levels early after transplantation reflect a
      disrupted microbiome and are associated with poor outcome.
AB  - Indole, which is produced from l-tryptophan by commensal bacteria expressing
      tryptophanase, not only is an important intercellular signal in microbial
      communities, but also modulates mucosal barrier function and expression of pro-
      and anti-inflammatory genes by intestinal epithelial cells. Here, we hypothesized
      that decreased urinary excretion of 3-indoxyl sulfate (3-IS), the major conjugate
      of indole found in humans, may be a marker of gut microbiota disruption and
      increased risk of developing gastrointestinal (GI) graft-versus-host-disease.
      Using liquid chromatography/tandem mass spectrometry, 3-IS was determined in
      urine specimens collected weekly within the first 28 days after allogeneic stem
      cell transplantation (ASCT) in 131 patients. Low 3-IS levels within the first 10
      days after ASCT were associated with significantly higher transplant-related
      mortality (P = .017) and worse overall survival (P = .05) 1 year after ASCT.
      Least absolute shrinkage and selection operator regression models trained on log
      normalized counts of 763 operational taxonomic units derived from next-generation
      sequencing of the hypervariable V3 region of the 16S ribosomal RNA gene showed
      members of the families of Lachnospiraceae and Ruminococcaceae of the class of
      Clostridia to be associated with high urinary 3-IS levels, whereas members of the
      class of Bacilli were associated with low 3-IS levels. Risk factors of early
      suppression of 3-IS levels were the type of GI decontamination (P = .01), early
      onset of antibiotic treatment (P = .001), and recipient NOD2/CARD15 genotype (P =
      .04). In conclusion, our findings underscore the relevance of microbiota-derived
      indole and metabolites thereof in mucosal integrity and protection from
      inflammation. 

PMID- 26209658
TI  - Autophagy is induced upon platelet activation and is essential for hemostasis and
      thrombosis.
AB  - Autophagy is important for maintaining cellular homeostasis, and thus its
      deficiency is implicated in a broad spectrum of human diseases. Its role in
      platelet function has only recently been examined. Our biochemical and imaging
      studies demonstrate that the core autophagy machinery exists in platelets, and
      that autophagy is constitutively active in resting platelets. Moreover, autophagy
      is induced upon platelet activation, as indicated by agonist-induced loss of the
      autophagy marker LC3II. Additional experiments, using inhibitors of platelet
      activation, proteases, and lysosomal acidification, as well as platelets from
      knockout mouse strains, show that agonist-induced LC3II loss is a consequence of
      platelet signaling cascades and requires proteases, acidic compartments, and
      membrane fusion. To assess the physiological role of platelet autophagy, we
      generated a mouse strain with a megakaryocyte- and platelet-specific deletion of
      Atg7, an enzyme required for LC3II production. Ex vivo analysis of platelets from
      these mice shows modest defects in aggregation and granule cargo packaging.
      Although these mice have normal platelet numbers and size distributions, they
      exhibit a robust bleeding diathesis in the tail-bleeding assay and a prolonged
      occlusion time in the FeCl3-induced carotid injury model. Our results demonstrate
      that autophagy occurs in platelets and is important for hemostasis and
      thrombosis. 

PMID- 26209660
TI  - Platelet-derived VWF is not essential for normal thrombosis and hemostasis but
      fosters ischemic stroke injury in mice.
AB  - Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both
      endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in
      alpha-granules of platelets and is enriched in hyperactive "ultra-large" VWF
      multimers. To elucidate the specific contribution of platelet VWF in hemostasis
      and thrombosis, we performed crossed bone marrow transplantations between
      C57BL/6J and Vwf(-/-) mice to generate chimeric mice. Chimeric mice specifically
      lacking platelet VWF showed normal tail bleeding and carotid artery thrombosis,
      similar to wild-type mice. Chimeric mice with VWF present only in platelets were
      not able to support normal thrombosis and hemostasis. However, using a mouse
      model of transient middle cerebral artery occlusion, we observed that cerebral
      infarct sizes and fibrin(ogen) deposition in chimeric mice with only platelet VWF
      were significantly increased compared with Vwf(-/-) mice (P < .01). Blocking of
      the platelet VWF-glycoprotein (GP)Ib interaction abrogated this platelet VWF
      mediated injury. These data suggest that whereas platelet-derived VWF does not
      play a crucial role in hemostasis and arterial thrombosis, it aggravates thrombo
      inflammatory diseases such as stroke via a GPIb-dependent mechanism. 

PMID- 26209661
TI  - Suppression of in vitro megakaryopoiesis by maternal sera containing anti-HPA-1a
      antibodies.
AB  - Incompatibility of the human platelet antigen-1 (HPA-1) system is the most common
      cause of fetal/neonatal alloimmune thrombocytopenia (F/NAIT) and is thought to be
      mediated by accelerated clearance of antibody-opsonized fetal platelets. We
      evaluated the effect of maternal sera containing anti-HPA-1a antibodies (F/NAIT
      sera) on in vitro megakaryopoiesis. Compared with control maternal sera, 14 out
      of 17 F/NAIT sera significantly reduced megakaryocyte (MK) number. This finding
      was associated with increased apoptosis and cell death of early MKs/MK
      progenitors, but normal maturation and differentiation of surviving MKs. An
      analysis of platelet counts in infants born to mothers following antenatal
      intravenous immunoglobulin (IVIG) +/- prednisone therapy demonstrated a
      significant and moderately strong correlation between the MK growth in cultures
      and the infants' platelet counts at birth. These findings suggest that maternal
      anti-HPA-1a antibodies can suppress fetal megakaryopoiesis by inducing early cell
      death and that this influences the neonatal platelet count. Thus, the ability of
      maternal antibodies to suppress MK growth is a potential predictive factor for
      the fetal response to maternal IVIG therapy. 

PMID- 26209662
TI  - Novel Glucose-1-Phosphatase with High Phytase Activity and Unusual Metal Ion
      Activation from Soil Bacterium Pantoea sp. Strain 3.5.1.
AB  - Phosphorus is an important macronutrient, but its availability in soil is
      limited. Many soil microorganisms improve the bioavailability of phosphate by
      releasing it from various organic compounds, including phytate. To investigate
      the diversity of phytate-hydrolyzing bacteria in soil, we sampled soils of
      various ecological habitats, including forest, private homesteads, large
      agricultural complexes, and urban landscapes. Bacterial isolate Pantoea sp.
      strain 3.5.1 with the highest level of phytase activity was isolated from forest
      soil and investigated further. The Pantoea sp. 3.5.1 agpP gene encoding a novel
      glucose-1-phosphatase with high phytase activity was identified, and the
      corresponding protein was purified to apparent homogeneity, sequenced by mass
      spectroscopy, and biochemically characterized. The AgpP enzyme exhibits maximum
      activity and stability at pH 4.5 and at 37 degrees C. The enzyme belongs to a
      group of histidine acid phosphatases and has the lowest Km values toward phytate,
      glucose-6-phosphate, and glucose-1-phosphate. Unexpectedly, stimulation of
      enzymatic activity by several divalent metal ions was observed for the AgpP
      enzyme. High-performance liquid chromatography (HPLC) and high-performance ion
      chromatography (HPIC) analyses of phytate hydrolysis products identify dl-myo
      inositol 1,2,4,5,6-pentakisphosphate as the final product of the reaction,
      indicating that the Pantoea sp. AgpP glucose-1-phosphatase can be classified as a
      3-phytase. The identification of the Pantoea sp. AgpP phytase and its unusual
      regulation by metal ions highlight the remarkable diversity of phosphorus
      metabolism regulation in soil bacteria. Furthermore, our data indicate that
      natural forest soils harbor rich reservoirs of novel phytate-hydrolyzing enzymes
      with unique biochemical features. 

PMID- 26209663
TI  - Fine-Tuning of Photoautotrophic Protein Production by Combining Promoters and
      Neutral Sites in the Cyanobacterium Synechocystis sp. Strain PCC 6803.
AB  - Cyanobacteria are photosynthetic cell factories that use solar energy to convert
      CO2 into useful products. Despite this attractive feature, the development of
      tools for engineering cyanobacterial chassis has lagged behind that for
      heterotrophs such as Escherichia coli or Saccharomyces cerevisiae. Heterologous
      genes in cyanobacteria are often integrated at presumptively "neutral"
      chromosomal sites, with unknown effects. We used transcriptome sequencing (RNA
      seq) data for the model cyanobacterium Synechocystis sp. strain PCC 6803 to
      identify neutral sites from which no transcripts are expressed. We characterized
      the two largest such sites on the chromosome, a site on an endogenous plasmid,
      and a shuttle vector by integrating an enhanced yellow fluorescent protein (EYFP)
      expression cassette expressed from either the Pcpc560 or the Ptrc1O promoter into
      each locus. Expression from the endogenous plasmid was as much as 14-fold higher
      than that from the chromosome, with intermediate expression from the shuttle
      vector. The expression characteristics of each locus correlated predictably with
      the promoters used. These findings provide novel, characterized tools for
      synthetic biology and metabolic engineering in cyanobacteria. 

PMID- 26209664
TI  - Transcriptomic Analysis of the Adaptation of Listeria monocytogenes to Growth on
      Vacuum-Packed Cold Smoked Salmon.
AB  - The foodborne pathogen Listeria monocytogenes is able to survive and grow in
      ready-to-eat foods, in which it is likely to experience a number of environmental
      stresses due to refrigerated storage and the physicochemical properties of the
      food. Little is known about the specific molecular mechanisms underlying survival
      and growth of L. monocytogenes under different complex conditions on/in specific
      food matrices. Transcriptome sequencing (RNA-seq) was used to understand the
      transcriptional landscape of L. monocytogenes strain H7858 grown on cold smoked
      salmon (CSS; water phase salt, 4.65%; pH 6.1) relative to that in modified brain
      heart infusion broth (MBHIB; water phase salt, 4.65%; pH 6.1) at 7 degrees C.
      Significant differential transcription of 149 genes was observed (false-discovery
      rate [FDR], <0.05; fold change, >=2.5), and 88 and 61 genes were up- and
      downregulated, respectively, in H7858 grown on CSS relative to the genes in H7858
      grown in MBHIB. In spite of these differences in transcriptomes under these two
      conditions, growth parameters for L. monocytogenes were not significantly
      different between CSS and MBHIB, indicating that the transcriptomic differences
      reflect how L. monocytogenes is able to facilitate growth under these different
      conditions. Differential expression analysis and Gene Ontology enrichment
      analysis indicated that genes encoding proteins involved in cobalamin
      biosynthesis as well as ethanolamine and 1,2-propanediol utilization have
      significantly higher transcript levels in H7858 grown on CSS than in that grown
      in MBHIB. Our data identify specific transcriptional profiles of L. monocytogenes
      growing on vacuum-packaged CSS, which may provide targets for the development of
      novel and improved strategies to control L. monocytogenes growth on this ready-to
      eat food. 

PMID- 26209665
TI  - A Strategy for Generating a Broad-Spectrum Monoclonal Antibody and Soluble Single
      Chain Variable Fragments against Plant Potyviruses.
AB  - Potyviruses are major pathogens that often cause mixed infection in calla lilies.
      To reduce the time and cost of virus indexing, a detection method for the
      simultaneous targeting of multiple potyviruses was developed by generating a
      broad-spectrum monoclonal antibody (MAb) for detecting the greatest possible
      number of potyviruses. The conserved 121-amino-acid core regions of the capsid
      proteins of Dasheen mosaic potyvirus (DsMV), Konjak mosaic potyvirus (KoMV), and
      Zantedeschia mild mosaic potyvirus (ZaMMV) were sequentially concatenated and
      expressed as a recombinant protein for immunization. After hybridoma cell fusion
      and selection, one stable cell line that secreted a group-specific antibody,
      named C4 MAb, was selected. In the reaction spectrum test, the C4 MAb detected at
      least 14 potyviruses by indirect enzyme-linked immunosorbent assay (I-ELISA) and
      Western blot analysis. Furthermore, the variable regions of the heavy (VH) and
      light (VL) chains of the C4 MAb were separately cloned and constructed as single
      chain variable fragments (scFvs) for expression in Escherichia coli. Moreover,
      the pectate lyase E (PelE) signal peptide of Erwinia chrysanthemi S3-1 was added
      to promote the secretion of C4 scFvs into the medium. According to Western blot
      analysis and I-ELISA, the soluble C4 scFv (VL-VH) fragment showed a binding
      specificity similar to that of the C4 MAb. Our results demonstrate that a
      recombinant protein derived from fusion of the conserved regions of viral
      proteins has the potential to produce a broad-spectrum MAb against a large group
      of viruses and that the PelE signal peptide can improve the secretion of scFvs in
      E. coli. 

PMID- 26209666
TI  - A Continuous Culture System for Assessing Microbial Activities in the
      Piezosphere.
AB  - Continuous culture under elevated pressures is an important technique for
      expanding the exploration of microbial growth and survival in extreme
      environments associated with the deep biosphere. Here we present a benchtop
      stirred continuous culture bioreactor capable of withstanding temperatures
      ranging from 25 to 120 degrees C and pressures as high as 69 MPa. The system is
      configured to allow the employment of media enriched in dissolved gases, under
      oxic or anoxic conditions, while permitting periodic sampling of the incubated
      organisms with minimal physical/chemical disturbance inside the reactor. In a
      pilot experiment, the fermentative growth of the thermopiezophilic bacterium
      Marinitoga piezophila was investigated continuously for 382 h at 65 degrees C and
      at pressures ranging from 0.1 to 40 MPa while the medium flow rate was varied
      from 2 to 0.025 ml/min. The enhanced growth observed at 30 and 40 MPa and 0.025
      ml/min supports the pressure preferences of M. piezophila when grown
      fermentatively. This assay successfully demonstrates the capabilities of the
      bioreactor for continuous culturing at a variety of dilution rates, pressures,
      and temperatures. We anticipate that this technology will accelerate our
      understanding of the physiological and metabolic status of microorganisms under
      temperature, pressure, and energy regimes resembling those of the Earth's
      piezosphere. 

PMID- 26209667
TI  - Origin of the Outbreak in France of Pseudomonas syringae pv. actinidiae Biovar 3,
      the Causal Agent of Bacterial Canker of Kiwifruit, Revealed by a Multilocus
      Variable-Number Tandem-Repeat Analysis.
AB  - The first outbreaks of bacterial canker of kiwifruit caused by Pseudomonas
      syringae pv. actinidiae biovar 3 were detected in France in 2010. P. syringae pv.
      actinidiae causes leaf spots, dieback, and canker that sometimes lead to the
      death of the vine. P. syringae pv. actinidifoliorum, which is pathogenic on kiwi
      as well, causes only leaf spots. In order to conduct an epidemiological study to
      track the spread of the epidemics of these two pathogens in France, we developed
      a multilocus variable-number tandem-repeat (VNTR) analysis (MLVA). MLVA was
      conducted on 340 strains of P. syringae pv. actinidiae biovar 3 isolated in
      Chile, China, France, Italy, and New Zealand and on 39 strains of P. syringae pv.
      actinidifoliorum isolated in Australia, France, and New Zealand. Eleven
      polymorphic VNTR loci were identified in the genomes of P. syringae pv.
      actinidiae biovar 3 ICMP 18744 and of P. syringae pv. actinidifoliorum ICMP
      18807. MLVA enabled the structuring of P. syringae pv. actinidiae biovar 3 and P.
      syringae pv. actinidifoliorum strains in 55 and 16 haplotypes, respectively. MLVA
      and discriminant analysis of principal components revealed that strains isolated
      in Chile, China, and New Zealand are genetically distinct from P. syringae pv.
      actinidiae strains isolated in France and in Italy, which appear to be closely
      related at the genetic level. In contrast, no structuring was observed for P.
      syringae pv. actinidifoliorum. We developed an MLVA scheme to explore the
      diversity within P. syringae pv. actinidiae biovar 3 and to trace the dispersal
      routes of epidemic P. syringae pv. actinidiae biovar 3 in Europe. We suggest
      using this MLVA scheme to trace the dispersal routes of P. syringae pv.
      actinidiae at a global level. 

PMID- 26209668
TI  - Distinct SagA from Hospital-Associated Clade A1 Enterococcus faecium Strains
      Contributes to Biofilm Formation.
AB  - Enterococcus faecium is an important nosocomial pathogen causing biofilm-mediated
      infections. Elucidation of E. faecium biofilm pathogenesis is pivotal for the
      development of new strategies to treat these infections. In several bacteria,
      extracellular DNA (eDNA) and proteins act as matrix components contributing to
      biofilm development. In this study, we investigated biofilm formation capacity
      and the roles of eDNA and secreted proteins for 83 E. faecium strains with
      different phylogenetic origins that clustered in clade A1 and clade B. Although
      there was no significant difference in biofilm formation between E. faecium
      strains from these two clades, the addition of DNase I or proteinase K to
      biofilms demonstrated that eDNA is essential for biofilm formation in most E.
      faecium strains, whereas proteolysis impacted primarily biofilms of E. faecium
      clade A1 strains. Secreted antigen A (SagA) was the most abundant protein in
      biofilms from E. faecium clade A1 and B strains, although its localization
      differed between the two groups. sagA was present in all sequenced E. faecium
      strains, with a consistent difference in the repeat region between the clades,
      which correlated with the susceptibility of biofilms to proteinase K. This
      indicates an association between the SagA variable repeat profile and the
      localization and contribution of SagA in E. faecium biofilms. 

PMID- 26209669
TI  - Roles of Thermophiles and Fungi in Bitumen Degradation in Mostly Cold Oil Sands
      Outcrops.
AB  - Oil sands are surface exposed in river valley outcrops in northeastern Alberta,
      where flat slabs (tablets) of weathered, bitumen-saturated sandstone can be
      retrieved from outcrop cliffs or from riverbeds. Although the average yearly
      surface temperature of this region is low (0.7 degrees C), we found that the
      temperatures of the exposed surfaces of outcrop cliffs reached 55 to 60 degrees C
      on sunny summer days, with daily maxima being 27 to 31 degrees C. Analysis of the
      cooccurrence of taxa derived from pyrosequencing of 16S/18S rRNA genes indicated
      that an aerobic microbial network of fungi and hydrocarbon-, methane-, or acetate
      oxidizing heterotrophic bacteria was present in all cliff tablets. Metagenomic
      analyses indicated an elevated presence of fungal cytochrome P450 monooxygenases
      in these samples. This network was distinct from the heterotrophic community
      found in riverbeds, which included fewer fungi. A subset of cliff tablets had a
      network of anaerobic and/or thermophilic taxa, including methanogens, Firmicutes,
      and Thermotogae, in the center. Long-term aerobic incubation of outcrop samples
      at 55 degrees C gave a thermophilic microbial community. Analysis of residual
      bitumen with a Fourier transform ion cyclotron resonance mass spectrometer
      indicated that aerobic degradation proceeded at 55 degrees C but not at 4 degrees
      C. Little anaerobic degradation was observed. These results indicate that bitumen
      degradation on outcrop surfaces is a largely aerobic process with a minor
      anaerobic contribution and is catalyzed by a consortium of bacteria and fungi.
      Bitumen degradation is stimulated by periodic high temperatures on outcrop
      cliffs, which cause significant decreases in bitumen viscosity. 

PMID- 26209670
TI  - Aspergillus glaucus Aquaglyceroporin Gene glpF Confers High Osmosis Tolerance in
      Heterologous Organisms.
AB  - Aquaglyceroporins (GlpFs) that transport glycerol along with water and other
      uncharged solutes are involved in osmoregulation in myriad species. Fungal
      species form a large group of eukaryotic organisms, and their GlpFs may be
      diverse, exhibiting various activities. However, few filamentous fungal GlpFs
      have been biologically investigated. Here, a glpF gene from the halophilic fungus
      Aspergillus glaucus (AgglpF) was verified to be a channel of water or glycerol in
      Xenopus laevis oocytes and was further functionally analyzed in three
      heterologous systems. In Saccharomyces cerevisiae, cells overexpressing AgglpF
      possessed significant tolerance of drought, salt, and certain metal ions. AgglpF
      was then characterized in the filamentous fungus of Neurospora crassa. Based on
      the N. crassa aquaporin gene (NcAQP) disruption mutant (the Deltaaqp mutant), a
      series of complementary strains carrying NcAQP and AgglpF and three asparagine
      proline-alanine-gene (NPA)-deleted AgglpF fragments were created. As revealed by
      salt resistance analysis, the AgglpF complementary strain possessed the highest
      salt resistance among the tested strains. In addition, the intracellular glycerol
      content in the AgglpF complementary strain was markedly higher than that in the
      other strains. The AgGlpF-green fluorescent protein (GFP) fusion protein was
      subcellularly localized in the plasma membrane of onion epidermal cells,
      suggesting that AgglpF functions in plants. Indeed, when AgglpF was expressed in
      Arabidopsis thaliana, transgenic lines survived under conditions of high osmotic
      stress and under conditions of drought stress in particular. Overall, our results
      revealed that AgGlpF as a water/glycerol transporter is required for survival of
      both fungi and plants under conditions of high osmotic stress and may have value
      in applications in genetic engineering for generating high salt and drought
      resistance. 

PMID- 26209671
TI  - The Bacterial Communities of Full-Scale Biologically Active, Granular Activated
      Carbon Filters Are Stable and Diverse and Potentially Contain Novel Ammonia
      Oxidizing Microorganisms.
AB  - The bacterial community composition of the full-scale biologically active,
      granular activated carbon (BAC) filters operated at the St. Paul Regional Water
      Services (SPRWS) was investigated using Illumina MiSeq analysis of PCR-amplified
      16S rRNA gene fragments. These bacterial communities were consistently diverse
      (Shannon index, >4.4; richness estimates, >1,500 unique operational taxonomic
      units [OTUs]) throughout the duration of the 12-month study period. In addition,
      only modest shifts in the quantities of individual bacterial populations were
      observed; of the 15 most prominent OTUs, the most highly variable population (a
      Variovorax sp.) modulated less than 13-fold over time and less than 8-fold from
      filter to filter. The most prominent population in the profiles was a Nitrospira
      sp., representing 13 to 21% of the community. Interestingly, very few of the
      known ammonia-oxidizing bacteria (AOB; <0.07%) and no ammonia-oxidizing Archaea
      were detected in the profiles. Quantitative PCR of amoA genes, however, suggested
      that AOB were prominent in the bacterial communities (amoA/16S rRNA gene ratio, 1
      to 10%). We conclude, therefore, that the BAC filters at the SPRWS potentially
      contained significant numbers of unidentified and novel ammonia-oxidizing
      microorganisms that possess amoA genes similar to those of previously described
      AOB. 

PMID- 26209673
TI  - Effects of Chicken Litter Storage Time and Ammonia Content on Thermal Resistance
      of Desiccation-Adapted Salmonella spp.
AB  - Broiler chicken litter was kept as a stacked heap on a poultry farm, and samples
      were collected up to 9 months of storage. Chicken litter inoculated with
      desiccation-adapted Salmonella cells was heat-treated at 75, 80, 85, and 150
      degrees C. Salmonella populations decreased in all these samples during heat
      treatment, and the inactivation rates became lower in chicken litter when storage
      time was extended from 0 to 6 months. There was no significant difference (P >
      0.05) in thermal resistance of Salmonella in 6- and 9-month litter samples,
      indicating that a threshold for thermal resistance was reached after 6 months.
      Overall, the thermal resistance of Salmonella in chicken litter was affected by
      the storage time of the litter. The changes in some chemical, physical, and
      microbiological properties during storage could possibly contribute to this
      difference. Moisture and ammonia could be two of the most significant factors
      influencing the thermal resistance of Salmonella cells in chicken litter. Our
      results emphasize the importance of adjusting time and temperature conditions for
      heat processing chicken litter when it is removed from the chicken house at
      different time intervals. 

PMID- 26209672
TI  - Exposure of Salmonella enterica Serovar Typhimurium to Three Humectants Used in
      the Food Industry Induces Different Osmoadaptation Systems.
AB  - Common salt (NaCl) is frequently used by the food industry to add flavor and to
      act as a humectant in order to reduce the water content of a food product. The
      improved health awareness of consumers is leading to a demand for food products
      with reduced salt content; thus, manufacturers require alternative water activity
      reducing agents which elicit the same general effects as NaCl. Two examples
      include KCl and glycerol. These agents lower the water activity of a food matrix
      and also contribute to limit the growth of the microbiota, including foodborne
      pathogens. Little is currently known about how foodborne pathogens respond to
      these water activity-lowering agents. Here we examined the response of Salmonella
      enterica serovar Typhimurium 4/74 to NaCl, KCl, and glycerol at three time
      points, using a constant water activity level, compared with the response of a
      control inoculum. All conditions induced the upregulation of gluconate metabolic
      genes after 6 h of exposure. Bacteria exposed to NaCl and KCl demonstrated the
      upregulation of the osmoprotective transporter mechanisms encoded by the proP,
      proU, and osmU (STM1491 to STM1494) genes. Glycerol exposure elicited the
      downregulation of these osmoadaptive mechanisms but stimulated an increase in
      lipopolysaccharide and membrane protein-associated genes after 1 h. The most
      extensive changes in gene expression occurred following exposure to KCl. Because
      many of these genes were of unknown function, further characterization may
      identify KCl-specific adaptive processes that are not stimulated by NaCl. This
      study shows that the response of S. Typhimurium to different humectants does not
      simply reflect reduced water activity and likely involves systems that are linked
      to specific humectants. 

PMID- 26209674
TI  - Seagrass (Zostera marina) Colonization Promotes the Accumulation of Diazotrophic
      Bacteria and Alters the Relative Abundances of Specific Bacterial Lineages
      Involved in Benthic Carbon and Sulfur Cycling.
AB  - Seagrass colonization changes the chemistry and biogeochemical cycles mediated by
      microbes in coastal sediments. In this study, we molecularly characterized the
      diazotrophic assemblages and entire bacterial community in surface sediments of a
      Zostera marina-colonized coastal lagoon in northern China. Higher nitrogenase
      gene (nifH) copy numbers were detected in the sediments from the vegetated region
      than in the sediments from the unvegetated region nearby. The nifH phylotypes
      detected were mostly affiliated with the Geobacteraceae, Desulfobulbus,
      Desulfocapsa, and Pseudomonas. Redundancy analysis based on terminal restriction
      fragment length polymorphism analysis showed that the distribution of nifH
      genotypes was mostly shaped by the ratio of total organic carbon to total organic
      nitrogen, the concentration of cadmium in the sediments, and the pH of the
      overlying water. High-throughput sequencing and phylogenetic analyses of
      bacterial 16S rRNA genes also indicated the presence of Geobacteraceae and
      Desulfobulbaceae phylotypes in these samples. A comparison of these results with
      those of previous studies suggests the prevalence and predominance of iron(III)
      reducing Geobacteraceae and sulfate-reducing Desulfobulbaceae diazotrophs in
      coastal sedimentary environments. Although the entire bacterial community
      structure was not significantly different between these two niches, Desulfococcus
      (Deltaproteobacteria) and Anaerolineae (Chloroflexi) presented with much higher
      proportions in the vegetated sediments, and Flavobacteriaceae (Bacteroidetes)
      occurred more frequently in the bare sediments. These data suggest that the high
      bioavailability of organic matter (indicated by relatively lower carbon-to
      nitrogen ratios) and the less-reducing anaerobic condition in vegetated sediments
      may favor Desulfococcus and Anaerolineae lineages, which are potentially
      important populations in benthic carbon and sulfur cycling in the highly
      productive seagrass ecosystem. 

PMID- 26209675
TI  - Improvement in Thermostability of an Achaetomium sp. Strain Xz8
      Endopolygalacturonase via the Optimization of Charge-Charge Interactions.
AB  - Improving enzyme thermostability is of importance for widening the spectrum of
      application of enzymes. In this study, a structure-based rational design approach
      was used to improve the thermostability of a highly active, wide-pH-range
      adaptable, and stable endopolygalacturonase (PG8fn) from Achaetomium sp. strain
      Xz8 via the optimization of charge-charge interactions. By using the enzyme
      thermal stability system (ETSS), two residues--D244 and D299--were inferred to be
      crucial contributors to thermostability. Single (D244A and D299R) and double
      (D244A/D299R) mutants were then generated and compared with the wild type. All
      mutants showed improved thermal properties, in the order D244A < D299R <
      D244A/D299R. In comparison with PG8fn, D244A/D299R showed the most pronounced
      shifts in temperature of maximum enzymatic activity (Tmax), temperature at which
      50% of the maximal activity of an enzyme is retained (T50), and melting
      temperature (Tm), of about 10, 17, and 10.2 degrees C upward, respectively, with
      the half-life (t1/2) extended by 8.4 h at 50 degrees C and 45 min at 55 degrees
      C. Another distinguishing characteristic of the D244A/D299R mutant was its
      catalytic activity, which was comparable to that of the wild type (23,000 +/- 130
      U/mg versus 28,000 +/- 293 U/mg); on the other hand, it showed more residual
      activity (8,400 +/- 83 U/mg versus 1,400 +/- 57 U/mg) after the feed pelleting
      process (80 degrees C and 30 min). Molecular dynamics (MD) simulation studies
      indicated that mutations at sites D244 and D299 lowered the overall root mean
      square deviation (RMSD) and consequently increased the protein rigidity. This
      study reveals the importance of charge-charge interactions in protein
      conformation and provides a viable strategy for enhancing protein stability.

PMID- 26209676
TI  - Topographical Mapping of the Rainbow Trout (Oncorhynchus mykiss) Microbiome
      Reveals a Diverse Bacterial Community with Antifungal Properties in the Skin.
AB  - The mucosal surfaces of wild and farmed aquatic vertebrates face the threat of
      many aquatic pathogens, including fungi. These surfaces are colonized by diverse
      symbiotic bacterial communities that may contribute to fight infection. Whereas
      the gut microbiome of teleosts has been extensively studied using pyrosequencing,
      this tool has rarely been employed to study the compositions of the bacterial
      communities present on other teleost mucosal surfaces. Here we provide a
      topographical map of the mucosal microbiome of an aquatic vertebrate, the rainbow
      trout (Oncorhynchus mykiss). Using 16S rRNA pyrosequencing, we revealed novel
      bacterial diversity at each of the five body sites sampled and showed that body
      site is a strong predictor of community composition. The skin exhibited the
      highest diversity, followed by the olfactory organ, gills, and gut.
      Flectobacillus was highly represented within skin and gill communities. Principal
      coordinate analysis and plots revealed clustering of external sites apart from
      internal sites. A highly diverse community was present within the epithelium, as
      demonstrated by confocal microscopy and pyrosequencing. Using in vitro assays, we
      demonstrated that two Arthrobacter sp. skin isolates, a Psychrobacter sp. strain,
      and a combined skin aerobic bacterial sample inhibit the growth of Saprolegnia
      australis and Mucor hiemalis, two important aquatic fungal pathogens. These
      results underscore the importance of symbiotic bacterial communities of fish and
      their potential role for the control of aquatic fungal diseases. 

PMID- 26209677
TI  - Characterization of para-Nitrophenol-Degrading Bacterial Communities in River
      Water by Using Functional Markers and Stable Isotope Probing.
AB  - Microbial degradation is a major determinant of the fate of pollutants in the
      environment. para-Nitrophenol (PNP) is an EPA-listed priority pollutant with a
      wide environmental distribution, but little is known about the microorganisms
      that degrade it in the environment. We studied the diversity of active PNP
      degrading bacterial populations in river water using a novel functional marker
      approach coupled with [(13)C6]PNP stable isotope probing (SIP). Culturing
      together with culture-independent terminal restriction fragment length
      polymorphism analysis of 16S rRNA gene amplicons identified Pseudomonas syringae
      to be the major driver of PNP degradation in river water microcosms. This was
      confirmed by SIP-pyrosequencing of amplified 16S rRNA. Similarly, functional gene
      analysis showed that degradation followed the Gram-negative bacterial pathway and
      involved pnpA from Pseudomonas spp. However, analysis of maleylacetate reductase
      (encoded by mar), an enzyme common to late stages of both Gram-negative and Gram
      positive bacterial PNP degradation pathways, identified a diverse assemblage of
      bacteria associated with PNP degradation, suggesting that mar has limited use as
      a specific marker of PNP biodegradation. Both the pnpA and mar genes were
      detected in a PNP-degrading isolate, P. syringae AKHD2, which was isolated from
      river water. Our results suggest that PNP-degrading cultures of Pseudomonas spp.
      are representative of environmental PNP-degrading populations. 

PMID- 26209678
TI  - Genome-Wide Screening Identifies Six Genes That Are Associated with
      Susceptibility to Escherichia coli Microcin PDI.
AB  - The microcin PDI inhibits a diverse group of pathogenic Escherichia coli strains.
      Coculture of a single-gene knockout library (BW25113; n=3,985 mutants) against a
      microcin PDI-producing strain (E. coli 25) identified six mutants that were not
      susceptible (DeltaatpA, DeltaatpF, DeltadsbA, DeltadsbB, DeltaompF, and
      DeltaompR). Complementation of these genes restored susceptibility in all cases,
      and the loss of susceptibility was confirmed through independent gene knockouts
      in E. coli O157:H7 Sakai. Heterologous expression of E. coli ompF conferred
      susceptibility to Salmonella enterica and Yersinia enterocolitica strains that
      are normally unaffected by microcin PDI. The expression of chimeric OmpF and site
      directed mutagenesis revealed that the K47G48N49 region within the first
      extracellular loop of E. coli OmpF is a putative binding site for microcin PDI.
      OmpR is a transcriptional regulator for ompF, and consequently loss of
      susceptibility by the DeltaompR strain most likely is related to this function.
      Deletion of AtpA and AtpF, as well as AtpE and AtpH (missed in the original
      library screen), resulted in the loss of susceptibility to microcin PDI and the
      loss of ATP synthase function. Coculture of a susceptible strain in the presence
      of an ATP synthase inhibitor resulted in a loss of susceptibility, confirming
      that a functional ATP synthase complex is required for microcin PDI activity. In
      trans expression of ompF in the DeltadsbA and DeltadsbB strains did not restore a
      susceptible phenotype, indicating that these proteins are probably involved with
      the formation of disulfide bonds for OmpF or microcin PDI.

PMID- 26209679
TI  - Inhibition of HIV-1 gp41 expression with hammerhead ribozymes.
AB  - Despite great progress in the treatment of AIDS, HIV-1 remains one of the major
      concerns as a human pathogen. One of the therapeutic strategies against viral
      infections is the application of catalytic ribonucleic acids (ribozymes) that can
      significantly reduce expression of a target gene by site-specific hydrolysis of
      its mRNA. In the present paper, we report a study on the activity of several
      variants of hammerhead ribozymes targeting a conserved region within mRNA
      encoding HIV-1 envelope glycoprotein gp41. On the basis of the data from in vitro
      assays and gene silencing in the cultured cells, we propose a new hammerhead
      ribozyme targeting the gp41-encoding sequence that can be potentially used as a
      therapeutic agent in AIDS treatment. Moreover, we demonstrate that the hydrolytic
      activity of the ribozyme in the intracellular environment cannot be inferred
      solely from the results of in vitro experiments. 

PMID- 26209680
TI  - Loss of Interleukin 1 Receptor Antagonist Enhances Susceptibility to Ebola Virus
      Infection.
AB  - The current outbreak of Ebola virus (EBOV) infection in West Africa is
      unprecedented, with nearly 26 000 confirmed cases and >10 000 deaths.
      Comprehensive data on the pathogenesis of EBOV infection are lacking; however,
      recent studies suggested that fatal EBOV infections are characterized by
      dysregulation of the innate immune response and a subsequent cytokine storm.
      Specifically, several studies suggested that hypersecretion of interleukin 1
      receptor antagonist (IL-1Ra) correlates with lethal EBOV infections. To examine
      the significance of IL-1Ra in EBOV infections, we infected mice that lack the
      gene encoding IL-1Ra, Il1rn (IL-1RN-KO), and mice with wild-type Il1rn (IL-1RN
      WT) with a mouse-adapted EBOV (MA-EBOV). Infected IL-1RN-KO mice lost more weight
      and had a lower survival rate than IL-1RN-WT mice infected with MA-EBOV. In
      addition, IL-1RN-KO mice infected with wild-type EBOV, which does not cause
      lethal infection in adult immunocompetent mice, such as C57BL/6 mice, experienced
      greater weight loss than IL-1RN-WT mice infected with wild-type EBOV. Further
      studies revealed that the levels of 6 cytokines in spleens-IL-1alpha, IL-1beta,
      interleukin 12p40, interleukin 17, granulocyte colony-stimulating factor, and
      regulated on activation, normal T-cell expressed and secreted-were significantly
      different between IL-1RN-KO mice and IL-1RN-WT mice infected with MA-EBOV.
      Collectively, our data suggest that IL-1Ra may have a protective effect upon EBOV
      infection, likely by damping an overactive proinflammatory immune response. 

PMID- 26209682
TI  - Experimental Respiratory Infection of Marmosets (Callithrix jacchus) With Ebola
      Virus Kikwit.
AB  - Ebola virus (EBOV) causes a highly infectious and lethal hemorrhagic fever in
      primates with high fatality rates during outbreaks and EBOV may be exploited as a
      potential biothreat pathogen. There is therefore a need to develop and license
      appropriate medical countermeasures against this virus. To determine whether the
      common marmoset (Callithrix jacchus) would be an appropriate model to assess
      vaccines or therapies against EBOV disease (EVD), initial susceptibility,
      lethality and pathogenesis studies were performed. Low doses of EBOV-Kikwit,
      between 4 and 27 times the 50% tissue culture infectious dose, were sufficient to
      cause a lethal, reproducible infection. Animals became febrile between days 5 and
      6, maintaining a high fever before succumbing to EVD between 6 and 8 days after
      challenge. Typical signs of EVD were observed. Pathogenesis studies revealed that
      virus was isolated from the lungs of animals beginning on day 3 after challenge
      and from the liver, spleen and blood beginning on day 5. The most striking
      features were observed in animals that succumbed to infection, including high
      viral titers in all organs, increased levels of liver function enzymes and blood
      clotting times, decreased levels of platelets, multifocal moderate to severe
      hepatitis, and perivascular edema. 

PMID- 26209681
TI  - Multidistrict Outbreak of Marburg Virus Disease-Uganda, 2012.
AB  - In October 2012, a cluster of illnesses and deaths was reported in Uganda and was
      confirmed to be an outbreak of Marburg virus disease (MVD). Patients meeting the
      case criteria were interviewed using a standard investigation form, and blood
      specimens were tested for evidence of acute or recent Marburg virus infection by
      reverse transcription-polymerase chain reaction (RT-PCR) and antibody enzyme
      linked immunosorbent assay. The total count of confirmed and probable MVD cases
      was 26, of which 15 (58%) were fatal. Four of 15 laboratory-confirmed cases (27%)
      were fatal. Case patients were located in 4 different districts in Uganda,
      although all chains of transmission originated in Ibanda District, and the
      earliest case detected had an onset in July 2012. No zoonotic exposures were
      identified. Symptoms significantly associated with being a MVD case included
      hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing.
      Contact with a case patient and attending a funeral were also significantly
      associated with being a case. Average RT-PCR cycle threshold values for fatal
      cases during the acute phase of illness were significantly lower than those for
      nonfatal cases. Following the institution of contact tracing, active case
      surveillance, care of patients with isolation precautions, community
      mobilization, and rapid diagnostic testing, the outbreak was successfully
      contained 14 days after its initial detection. 

PMID- 26209683
TI  - Role of Coccidioides Antigen Testing in the Cerebrospinal Fluid for the Diagnosis
      of Coccidioidal Meningitis.
AB  - BACKGROUND: Coccidioidal meningitis (CM), a common cause of chronic meningitis in
      endemic area, is usually diagnosed by detection of anti-Coccidioides antibodies
      in cerebrospinal fluid (CSF), and findings may be negative in up to one-third of
      cases. CSF cultures and cytology are infrequently positive. Antigen detection has
      been used for the diagnosis of other forms of coccidioidomycosis and meningitis
      caused by other mycoses. The purpose of this study was to assess the diagnostic
      utility of CSF Coccidioides antigen (CAg) detection for the diagnosis of CM.
      METHODS: The medical records of patients with clinically suspected meningitis, in
      whom CSF was tested for Coccidioides antibodies and CAg, were retrospectively
      reviewed, and CSF CAg testing was prospectively conducted in patients with CM.
      All specimens were submitted for CAg testing. RESULTS: Thirty-six patients with
      42 episode of CM were studied. The sensitivity and specificity of CAg were 93%
      and 100%, respectively. Cultures of CSF were positive in 7%, antibodies were
      demonstrated by immunodiffusion in 67% and complement fixation in 70%, and
      immunoglobulin M and G antibodies were demonstrated by enzyme immunoassay in 8%
      and 85%, respectively. CONCLUSIONS: Testing CSF for CAg is a useful addition to
      diagnostic methods in suspected CM and complements testing with CSF antibodies
      and culture.

PMID- 26209684
TI  - Quantiferon-Gold Tuberculosis Test Cannot Detect Latent Tuberculosis in Patients
      With Leprosy.
AB  - Five of 10 paucibacillary leprosy patients were Quantiferon Gold (Q-G) positive
      with negative chest X-rays. Forty multibacillary leprosy patients were negative.
      Reports have shown 100% cross-reactivity of ESAT6 and CFP10 between Mycobacterium
      leprae and Mycobacterium tuberculosis. The Q-G test cannot detect latent
      tuberculosis in patients with leprosy. 

PMID- 26209685
TI  - Reply to Berger.

PMID- 26209686
TI  - Influenza, not Ebola, More Likely the Cause of 430 BCE Athenian Outbreak.

PMID- 26209687
TI  - Gradients of metabolite accumulation and redifferentiation of nutritive cells
      associated with vascular tissues in galls induced by sucking insects.
AB  - Plant cells respond to abiotic and biotic stimuli, which generate adaptive
      phenotypes in plant organs. In the case of plant galls, cell phenotypes are
      adaptive for the gall inducer and assume characteristics mainly linked to its
      protection and nutrition. Herein, the cytological development and histochemical
      profile of Nothotrioza cattleiani galls, a sucking insect, on the leaves of
      Psidium cattleianum are compared with those of other galls, especially N.
      myrtoidis galls, searching for conserved and divergent alterations in cell fates
      and cycles. Leaf cell fates are completely changed within galls, except for
      epidermal cells, but the comparison between Nothotrioza spp. galls shows
      conserved fates. Nevertheless, cytological development of N. cattleiani galls is
      different from the standby-redifferentiation of N. myrtoidis galls. Starch and
      lignins, and reducing sugars form centrifugal and centripetal gradients of
      accumulation, respectively. Proteins, total phenolics, terpenoids,
      proanthocyanidins and reactive oxygen species are detected in bidirectional
      gradients, i.e. weak or undetectable reaction in the median cortical cells that
      is gradually more intense in the cell layers towards the inner and outer surfaces
      of the gall. True nutritive cells associated with vascular tissues, together with
      the bidirectional gradients of metabolite accumulation, are herein reported for
      the first time in insect galls. The globoid galls of N. cattleiani, though macro
      morphologically similar to the galls of N. myrtoidis, are distinct and unique
      among insect galls, as far as the cellular, subcellular and histochemical traits
      are concerned. Thus, the traits of the galls on P. cattleianum studied herein
      represent the extended phenotypes of their inducers. 

PMID- 26209688
TI  - Aromatase inhibitors and bisphosphonates reduce deaths from breast cancer,
      studies show.

PMID- 26209689
TI  - Urinary incontinence a first presentation of central pontine myelinolysis: a case
      report.
AB  - An 84-year-old lady was treated for hyperosmolar hyperglycaemia with IV insulin,
      fluids and catheterisation for fluid balance monitoring. Trial without catheter
      failed as the patient complained of new-onset urinary incontinence and lack of
      awareness of bladder filling. In light of her breast cancer history, we excluded
      cauda equina. Ultrasound KUB showed an enlarged bladder. Whole-body MRI revealed
      a lesion in the pons which was highly suggestive of central pontine myelinolysis
      (CPM). Her electrolytes were normal throughout her admission; thus, the rapid
      fluctuation in osmolality, secondary to her hyperglycaemic state, was the likely
      cause of CPM. CPM has been reported secondary to hyperglycaemia; however, this is
      the first reported case of CPM presenting as urinary incontinence and loss of
      bladder sensation. 

PMID- 26209690
TI  - Beni Solow Award 2014.
AB  - The Beni Solow award for the best article published in the European Journal of
      Orthodontics in 2014 has been won by: Karoline Dreesen, Steven Swinnen, Koenraad
      Devriendt, and Carine Carels from Departments of Orthodontics and Human Genetics,
      Katholieke Universiteit Leuven, Belgium and Department of Orthodontics and
      Craniofacial Biology, Radboud University Nijmegen Medical Centre, the Netherlands
      for their article 'Tooth agenesis patterns and phenotype variation in a cohort of
      Belgian patients with hypodontia and oligodontia clustered in 79 families with
      their pedigrees' Eur J Orthod 2014 36(1), 99-106. This article can be accessed
      free of charge online at: www.ejo.oxfordjournals. org.

PMID- 26209691
TI  - Hopes rise for new Alzheimer's drug after secondary analysis.

PMID- 26209692
TI  - Clinical Utility of Ventricular Repolarization Dispersion for Real-Time Detection
      of Non-ST Elevation Myocardial Infarction in Emergency Departments.
AB  - BACKGROUND: A specific electrocardiographic (ECG) marker of ischemia would
      greatly improve the speed and accuracy of detecting and treating non-ST elevation
      myocardial infarction (NSTEMI). We hypothesize that ischemia induces ventricular
      repolarization dispersion (VRD), altering the T-wave before any ST segment
      deviation. We sought to evaluate the clinical utility of VRD to (1) detect NSTEMI
      cases in the emergency department (ED) and (2) identify NSTEMI cases at high risk
      for in-hospital major adverse cardiac events (MACEs). METHODS AND RESULTS: We
      continuously recorded 12-lead Holter ECGs from chest pain patients upon their
      arrival to the ED. VRD was quantified using principal component analysis of the
      12-lead ECG to compute a T-wave complexity ratio (ie, ratio of second to first
      eigenvectors of repolarization). Clinical outcomes were obtained from hospital
      records. The sample was composed mainly of older males (n=369; ages 63+/-12
      years; 63% males), and 92 (25%) had NSTEMI and 26 (7%) had MACEs. Baseline T-wave
      complexity ratio modestly correlated with peak troponin levels (r=0.41; P<0.001)
      and was a good classifier of NSTEMI events (area under the curve=0.70). An
      increased T-wave complexity ratio on the presenting ECG was strongly associated
      with NSTEMI (odds ratio [OR]=3.8 [2.1 to 5.8]) and in-hospital MACE (OR=8.2 [3.1
      to 21.5]). CONCLUSIONS: A simple measure of global VRD on the presenting 12-lead
      ECG correlates with ischemic myocardial injury and can discriminate NSTEMI cases
      very early during evaluation. Prospective studies should validate these findings
      and test whether VRD can guide therapy.

PMID- 26209693
TI  - Non-ST-Segment Elevation Myocardial Infarction: A Novel and Robust Approach for
      Early Detection of Patients at Risk.

PMID- 26209694
TI  - Transcriptome Analysis of Aspergillus flavus Reveals veA-Dependent Regulation of
      Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster.
AB  - The global regulatory veA gene governs development and secondary metabolism in
      numerous fungal species, including Aspergillus flavus. This is especially
      relevant since A. flavus infects crops of agricultural importance worldwide,
      contaminating them with potent mycotoxins. The most well-known are aflatoxins,
      which are cytotoxic and carcinogenic polyketide compounds. The production of
      aflatoxins and the expression of genes implicated in the production of these
      mycotoxins are veA dependent. The genes responsible for the synthesis of
      aflatoxins are clustered, a signature common for genes involved in fungal
      secondary metabolism. Studies of the A. flavus genome revealed many gene clusters
      possibly connected to the synthesis of secondary metabolites. Many of these
      metabolites are still unknown, or the association between a known metabolite and
      a particular gene cluster has not yet been established. In the present
      transcriptome study, we show that veA is necessary for the expression of a large
      number of genes. Twenty-eight out of the predicted 56 secondary metabolite gene
      clusters include at least one gene that is differentially expressed depending on
      presence or absence of veA. One of the clusters under the influence of veA is
      cluster 39. The absence of veA results in a downregulation of the five genes
      found within this cluster. Interestingly, our results indicate that the cluster
      is expressed mainly in sclerotia. Chemical analysis of sclerotial extracts
      revealed that cluster 39 is responsible for the production of aflavarin. 

PMID- 26209697
TI  - The dynamics of the bacterial diversity in the redox transition and anoxic zones
      of the Cariaco Basin assessed by parallel tag sequencing.
AB  - Massively parallel tag sequencing was applied to describe the bacterial diversity
      in the redox transition and anoxic zones of the Cariaco Basin. In total, 14
      samples from the Cariaco Basin were collected over a period of eight years from
      two stations. A total of 244 357 unique bacterial V6 amplicons were sequenced.
      The total number of operational taxonomic units (OTUs) found in this study was
      4692, with a range of 511-1491 OTUs per sample. Approximately 95% of the OTUs
      found in the redox transition zone and anoxic layers of Cariaco are represented
      by less than 50 amplicons suggesting that only about 5% of the bacterial OTUs are
      responsible for the bulk of the microbial processes in the basin redox transition
      and anoxic zones. The same dominant OTUs were observed across all eight years of
      sampling although periodic fluctuations in their proportion were apparent. No
      distinctive differences were observed between the bacterial communities from the
      redox transition and anoxic layers of the Cariaco Basin water column. The largest
      proportion of amplicons belongs to Gammaproteobacteria represented mostly by
      sulfide oxidizers, followed by Marine Group A (originally described as SAR406;
      Gordon and Giovannoni 1996), a group of uncultured bacteria hypothesized to be
      involved in metal reduction, and sulfate-reducing Deltaproteobacteria.
      Gammaproteobacteria, Deltaproteobacteria and Marine Group A make up 67-90% of all
      V6 amplicons sequenced in this study. This strongly suggests that the basin's
      microbial communities are actively involved in the sulfur-related metabolism and
      coupling of the sulfur and carbon cycles. According to detrended canonical
      correspondence analysis, ecological factors such as chemoautotrophy, nitrate and
      oxidized and reduced sulfur compounds influence the structuring and distribution
      of the Cariaco microbial communities. 

PMID- 26209695
TI  - The Octatricopeptide Repeat Protein Raa8 Is Required for Chloroplast trans
      Splicing.
AB  - The mRNA maturation of the tripartite chloroplast psaA gene from the green alga
      Chlamydomonas reinhardtii depends on various nucleus-encoded factors that
      participate in trans splicing of two group II introns. Recently, a multiprotein
      complex was identified that is involved in processing the psaA precursor mRNA.
      Using coupled tandem affinity purification (TAP) and mass spectrometry analyses
      with the trans-splicing factor Raa4 as a bait protein, we recently identified a
      multisubunit ribonucleoprotein (RNP) complex comprising the previously
      characterized trans-splicing factors Raa1, Raa3, Raa4, and Rat2 plus novel
      components. Raa1 and Rat2 share a structural motif, an octatricopeptide repeat
      (OPR), that presumably functions as an RNA interaction module. Two of the novel
      RNP complex components also exhibit a predicted OPR motif and were therefore
      considered potential trans-splicing factors. In this study, we selected bacterial
      artificial chromosome (BAC) clones encoding these OPR proteins and conducted
      functional complementation assays using previously generated trans-splicing
      mutants. Our assay revealed that the trans-splicing defect of mutant F19 was
      restored by a new factor we named RAA8; molecular characterization of
      complemented strains verified that Raa8 participates in splicing of the first
      psaA group II intron. Three of six OPR motifs are located in the C-terminal end
      of Raa8, which was shown to be essential for restoring psaA mRNA trans splicing.
      Our results support the important role played by OPR proteins in chloroplast RNA
      metabolism and also demonstrate that combining TAP and mass spectrometry with
      functional complementation studies represents a vigorous tool for identifying
      trans-splicing factors. 

PMID- 26209698
TI  - A new hypothesis about increased rates of schizophrenia among migrants.

PMID- 26209696
TI  - Intracellular sphingosine kinase 2-derived sphingosine-1-phosphate mediates
      epidermal growth factor-induced ezrin-radixin-moesin phosphorylation and cancer
      cell invasion.
AB  - The bioactive sphingolipid sphingosine-1-phosphate (S1P) mediates cellular
      proliferation, mitogenesis, inflammation, and angiogenesis. These biologies are
      mediated through S1P binding to specific GPCRs [sphingosine-1-phosphate receptor
      (S1PR)1-5] and some other less well-characterized intracellular targets. Ezrin
      radixin-moesin (ERM) proteins, a family of adaptor molecules linking the cortical
      actin cytoskeleton to the plasma membrane, are emerging as critical regulators of
      cancer invasion via regulation of cell morphology and motility. Recently, we
      identified S1P as an acute ERM activator (via phosphorylation) through its action
      on S1PR2. In this work, we dissect the mechanism of S1P generation downstream of
      epidermal growth factor (EGF) leading to ERM phosphorylation and cancer invasion.
      Using pharmacologic inhibitors, small interfering RNA technologies, and genetic
      approaches, we demonstrate that sphingosine kinase (SK)2, and not SK1, is
      essential and sufficient in EGF-mediated ERM phosphorylation in HeLa cells. In
      fact, knocking down SK2 decreased ERM activation 2.5-fold. Furthermore, we
      provide evidence that SK2 is necessary to mediate EGF-induced invasion. In
      addition, overexpressing SK2 causes a 2-fold increase in HeLa cell invasion.
      Surprisingly, and for the first time, we find that this event, although dependent
      on S1PR2 activation, does not generate and does not require extracellular S1P
      secretion, therefore introducing a potential novel model of autocrine/intracrine
      action of S1P that still involves its GPCRs. These results define new mechanistic
      insights for EGF-mediated invasion and novel actions of SK2, therefore setting
      the stage for novel targets in the treatment of growth factor-driven
      malignancies.

PMID- 26209699
TI  - Micro-identities, adjustment and stigma.

PMID- 26209700
TI  - Vocational rehabilitation improves insight and social functioning of people with
      schizophrenia.

PMID- 26209701
TI  - Nonsuicidal self-injury in Indian adolescents: Nonexistent or unacknowledged?
AB  - Nonsuicidal self-injury (NSSI) has been a neglected entity in low- and middle
      income countries (LMICs). In this correspondence (letter to the editor), authors
      are advocating for greater research in this area in LMICs as it will help to
      compare and contrast prevalence rates of NSSI in these countries with high-income
      countries (HICs), identify context-specific risk and protective factors to better
      understand the pathophysiology of NSSI and devise context-specific interventions
      resulting in improvement in adolescent mental health worldwide. 

PMID- 26209702
TI  - Capability to be healthy--Implications for prevention.

PMID- 26209703
TI  - Corrigendum.

PMID- 26209704
TI  - Can 'migraine' be defined?--Yes and we have to.

PMID- 26209705
TI  - Peripheral nerve field stimulation for trigeminal neuralgia, trigeminal
      neuropathic pain, and persistent idiopathic facial pain.
AB  - OBJECTIVE: Peripheral nerve field stimulation (PNFS) is a promising modality for
      treatment of intractable facial pain. However, evidence is sparse. We are
      therefore presenting our experience with this technique in a small patient
      cohort. METHODS: Records of 10 patients (five men, five women) with intractable
      facial pain who underwent implantation of one or several subcutaneous electrodes
      for trigeminal nerve field stimulation were retrospectively analyzed. Patients'
      data, including pain location, etiology, duration, previous treatments, long-term
      effects and complications, were evaluated. RESULTS: Four patients suffered from
      recurrent classical trigeminal neuralgia, one had classical trigeminal neuralgia
      and was medically unfit for microvascular decompression. Two patients suffered
      from trigeminal neuropathy attributed to multiple sclerosis, one from post
      herpetic neuropathy, one from trigeminal neuropathy following radiation therapy
      and one from persistent idiopathic facial pain. Average patient age was 74.2
      years (range 57-87), and average symptom duration was 10.6 years (range 2-17).
      Eight patients proceeded to implantation after successful trial. Average follow
      up after implantation was 11.3 months (range 5-28). Using the visual analog
      scale, average pain intensity was 9.3 (range 7-10) preoperatively and 0.75 (range
      0-3) postoperatively. Six patients reported absence of pain with stimulation; two
      had only slight constant pain without attacks. CONCLUSION: PNFS may be an
      effective treatment for refractory facial pain and yields high patient
      satisfaction.

PMID- 26209706
TI  - Home Help Service Staffs' Descriptions of Their Role in Promoting Everyday
      Activities Among Older People in Sweden Who Are Dependent on Formal Care.
AB  - The study aimed to explore how home help service staff described their role in
      improving the abilities of older people, in particular, older women with chronic
      pain who are dependent on formal care, to perform everyday activities. Three
      focus group interviews were conducted, and a qualitative inductive thematic
      content analysis was used. The analysis resulted in one theme: struggling to
      improve the care recipients' opportunities for independence but being inhibited
      by complex environmental factors. By encouraging the care recipients to perform
      everyday activities, the staff perceived themselves to both maintain and improve
      their care recipients' independence and quality of life. An important goal for
      society and health care professionals is to improve older people's abilities to
      "age in place" and to enable them to age independently while maintaining their
      quality of life. A key resource is home help service staff, and this resource
      should be utilized in the best possible way.

PMID- 26209707
TI  - Gluteal Augmentation With Liquid Silicone of Unknown Purity Causes Granulomas in
      an Adult Female: Case Report and Review of the Literature.
AB  - BACKGROUND: A 39-year-old woman presented with a history of relapsing painful
      erythema and progressive fibrosis of the lower back. Upon questioning, the
      patient admitted to receiving liquid silicone (LS) injections for gluteal
      augmentation abroad and was diagnosed with silicone migration, granulomatous
      reaction, and fibrosis of the lower back. OBJECTIVE: To review the history of LS
      injections for cosmetic soft tissue augmentation (STA) as well as its
      complications and potential treatments. METHODS: The author reviewed articles
      that involved the use of LS for STA and summarized their findings. RESULTS: The
      author summarizes the various treatments that have been described for
      inflammatory reactions following LS injection. CONCLUSION: The growth of cosmetic
      medical tourism and its inherent lack of after-care as well as patients' ability
      to obtain restricted products at home raise the likelihood of encountering
      granulomatous or fibrotic reactions to fillers during consultations. Physicians
      should have a structured approach to these patients.

PMID- 26209708
TI  - Disciplinary and Legal Actions Against Dermatologists in Canada.
AB  - BACKGROUND: Dermatologists face a litany of professional and legal risks in
      practice. OBJECTIVE: To review cases of disciplinary and legal action against
      dermatologists in Canada. METHODS: The Canadian Medical Protective Association,
      all 10 provincial medical colleges, and the Canadian Legal Information Institute
      were contacted to obtain data on legal or disciplinary action taken against
      dermatologists in their records. A literature review was performed regarding
      litigation against dermatologists in other countries. RESULTS: Six dermatologists
      in Canada faced disciplinary action in the last 5 to 30 years. Seven
      dermatologists and 5 other specialists in Canada faced lawsuits relating to
      dermatology in the last 1 to 144 years. Procedures and therapy are the most
      frequently sources of lawsuits against dermatologists both at home and abroad.
      CONCLUSION: Dermatologists need to remain vigilant to avoid disciplinary action
      and lawsuits from their increasing and varied interactions with patients.

PMID- 26209709
TI  - Validation of a new method for non-invasive assessment of vasomotor function.
AB  - BACKGROUND: Reactive hyperaemia induces a slowing of pulse wave velocity (PWV) in
      conduit arteries of healthy subjects (flow-mediated slowing (FMS)). This could be
      an alternative method for assessing peripheral vasomotor function to the gold
      standard method of flow-mediated dilatation (FMD) a more expensive and
      technically demanding technique. We aimed to assess the reproducibility of FMS in
      healthy participants and to test its ability to detect differences in vasomotor
      function in patients with familial hypercholesterolaemia (FH) and post
      lipoprotein apheresis (LA) treatment. METHODS: Altogether 25 healthy participants
      were studied on two occasions to assess reproducibility of FMS. In a case control
      study of 22 patients with FH and matched healthy controls, FMD and FMS were
      compared. An intervention study in 12 patients with FH looked at the impact of a
      single LA treatment on FMS assessed pre and post treatment. RESULTS: FMS
      demonstrated good reproducibility (coefficient of variation (CoV) 7.3%). Patients
      with FH had reduced FMS in comparison to matched healthy controls (FMS% FH -15.13
      +/- 5.04% vs controls -18.41 +/- 5.15%, p = 0.023), with no difference in FMD%
      between the two groups. A single LA treatment significantly improved FMS (pre 
      18.81 +/- 9.84 vs post -24.09 +/- 7.61%, p = 0.016). CONCLUSIONS: FMS is a
      reproducible technique, which is able to detect differences in vasomotor function
      both in a condition associated with endothelial dysfunction and following an
      acute intervention known to improve endothelial function. This simple technique
      has potential for accessible assessment of vasomotor function in clinical
      studies.

PMID- 26209710
TI  - RE: Androgen Deprivation With or Without Radiation Therapy for Clinically Node
      Positive Prostate Cancer.

PMID- 26209711
TI  - Response.

PMID- 26209713
TI  - Meeting the World's Need for Maintenance Dialysis.

PMID- 26209712
TI  - Maintenance Dialysis throughout the World in Years 1990 and 2010.
AB  - Rapidly rising global rates of chronic diseases portend a consequent rise in
      ESRD. Despite this, kidney disease is not included in the list of noncommunicable
      diseases (NCDs) targeted by the United Nations for 25% reduction by year 2025. In
      an effort to accurately report the trajectory and pattern of global growth of
      maintenance dialysis, we present the change in prevalence and incidence from 1990
      to 2010. Data were extracted from the Global Burden of Disease 2010 epidemiologic
      database. The results are on the basis of an analysis of data from worldwide
      national and regional renal disease registries and detailed systematic literature
      review for years 1980-2010. Incidence and prevalence estimates of provision of
      maintenance dialysis from this database were updated using a negative binomial
      Bayesian meta-regression tool for 187 countries. Results indicate substantial
      growth in utilization of maintenance dialysis in almost all world regions.
      Changes in population structure, changes in aging, and the worldwide increase in
      diabetes mellitus and hypertension explain a significant portion, but not all, of
      the increase because increased dialysis provision also accounts for a portion of
      the rise. These findings argue for the importance of inclusion of kidney disease
      among NCD targets for reducing premature death throughout the world. 

PMID- 26209715
TI  - Leg stereotypy disorder.

PMID- 26209714
TI  - Smaller kidney size at birth in South Asians: findings from the Born in Bradford
      birth cohort study.
AB  - BACKGROUND: Rates of advanced chronic kidney disease and renal replacement
      therapy are higher in South Asian than in white British populations. Low birth
      weight is also more frequent in South Asian populations and has been associated
      with increased risks of kidney disease, perhaps due to a reduced nephron
      endowment. METHODS: Using ultrasound scans at 34 weeks of gestation, we measured
      fetal kidney dimensions (transverse and anteroposterior diameters, length and
      circumference) and derived volume in a random sample of 872 white British and 715
      South Asian participants in the Born in Bradford cohort study. Kidney
      measurements were compared between ethnic groups. RESULTS: Birth weight for
      gestational age at 40 weeks was 200 g less in South Asian babies compared with
      white British babies. The mean kidney volume for gestational age was 16% lower in
      South Asian than in white British babies [8.79 versus 10.45 cm(3), difference
      1.66 cm(3) (95% confidence interval 1.40-1.93, P < 0.001)]. The difference was
      robust after adjustment for maternal age, socio-economic factors, marital status,
      body mass index, smoking and alcohol use in pregnancy, parity, baby's gender and
      birth weight for gestational age [adjusted difference 1.38 cm(3) (0.97-1.84), P <
      0.001]. There were smaller reductions in other fetal measures. CONCLUSION: South
      Asian babies have smaller kidneys compared with white British babies, even after
      adjusting for potential confounders including birth weight. This finding may
      contribute to increased risks of adult kidney disease in South Asian populations.

PMID- 26209716
TI  - Parkinson's disease without nigral degeneration: a pathological correlate of
      scans without evidence of dopaminergic deficit (SWEDD)?
AB  - OBJECTIVE: To describe 5 cases of Parkinson's disease lacking any detectable
      histopathology. BACKGROUND: The diagnosis of Parkinson's disease is supported
      histologically by the findings of alpha-synuclein immunopositive Lewy bodies and
      neurites and severe substantia nigra cell loss. Bradykinesia as defined by
      slowness of initiation of movement and a progressive reduction in speed and
      amplitude on finger tapping is a clinical correlate of pars compacta nigral
      degeneration. There are very few published cases of Parkinson's disease in which
      no pathological abnormality was found, and some of these cases were in hindsight
      thought to have probably been cases of indeterminate senile tremor or dystonic
      tremor. METHODS: Retrospective case notes review of the Queen Square Brain Bank
      archival collection and detailed neuropathological analysis of the selected
      cases. RESULTS: 5 cases considered to have Parkinson's disease by neurologists
      throughout the entirety of their illness that lacked any histopathological
      findings known to be associated with Parkinson's syndromes were identified out of
      a total number of 773 brains with a final clinical diagnosis of Parkinson's
      disease in the Queen Square Brain Bank. Retrospective case note analysis did not
      suggest dystonic tremor or indeterminate tremor in any of them. There was a
      reduction in tyrosine hydroxylase (TH) density in the striatum in these cases
      when compared with healthy controls, but not in the substantia nigra.
      CONCLUSIONS: Striatal dopamine deficiency without nigral cell loss is the most
      likely explanation for the clinical findings; other possible explanations include
      slowness due to comorbidities misinterpreted as bradykinesia, a tardive syndrome
      related to undisclosed previous neuroleptic exposure, or 'soft age-related'
      parkinsonian signs. These cases emphasise the need to regularly review the
      diagnosis in cases of suspected Parkinson's disease and highlight the need for
      precision in the neurological examination particularly of elderly patients. These
      cases may represent a distinct entity of diagnostic exclusion and may be
      considered one explanation for the radiological phenomenon of SWEDD (scans
      without evidence of dopaminergic deficit).

PMID- 26209721
TI  - Correction.

PMID- 26209720
TI  - Ubiquitin-specific protease 28 is overexpressed in human glioblastomas and
      contributes to glioma tumorigenicity by regulating MYC expression.
AB  - The transcription factor MYC, which is dysregulated in the majority of gliomas,
      is difficult to target directly. Deubiquitinase ubiquitin-specific protease 28
      (USP28) stabilizes oncogenic factors, including MYC. However, the contribution of
      USP28 in tumorigenesis, particularly in glioma, is unknown. Here, we determined
      the expression of USP28 and assessed its clinical significance in human glioma.
      We found that USP28 is overexpressed in human glioma but not in normal brain
      tissue. The level of USP28 protein expression in human glioma tissues was
      directly correlated with glioma grade. Meanwhile, the level of USP28 protein
      expression in human glioblastoma tissues was inversely correlated with patient
      survival. Enforced USP28 expression promotes SW1783 glioma cell proliferation.
      Moreover, gliomas that arose from USP28-transfected SW1783 cells displayed
      tumorigenicity in nude mouse model systems. Inhibition of USP28 expression in
      glioblastoma U373 cells suppressed anchorage-independent growth in vitro and
      tumorigenicity in vivo. Furthermore, USP28 regulates the expression of MYC
      protein, which is essential in USP28-induced cell growth in glioma cells. These
      results showed that USP28 is overexpressed in human glioblastomas and it
      contributes to glioma tumorigenicity. Therefore, USP28 could be a new target of
      therapy for human malignant glioma. 

PMID- 26209722
TI  - Correction.

PMID- 26209723
TI  - Safeguarding choice at the end of life.

PMID- 26209728
TI  - The hydrophobic rich N- and C-terminal tails of beta-catenin facilitate nuclear
      import.
AB  - This article was withdrawn by the authors before final publication on May 18,
      2015.

PMID- 26209727
TI  - Late onset neuropathy with spontaneous clinical remission in mice lacking the POZ
      domain of the transcription factor Myc-interacting zinc finger protein 1 (Miz1)
      in Schwann cells.

PMID- 26209729
TI  - Klotho expression in cervical cancer: differential expression in adenocarcinoma
      and squamous cell carcinoma.
AB  - AIMS: Klotho is a trans-membrane protein that serves as a tumour suppressor in a
      wide array of malignancies. Recent data suggest it as an epigenetically silenced
      tumour suppressor in cervical cancer. Yet, the expression pattern of klotho in
      cervical cancer has not been determined. We aimed to study the expression of
      klotho in squamous cell carcinomas (SQCC) and adenocarcinoma (ADC) of the cervix.
      METHODS: Klotho expression was analysed by immunohistochemistry in 44 SQCC
      samples, 38 ADC samples and the adjacent normal tissue. For each sample,
      percentage of positive stained cells, staining intensity and a combined staining
      score were recorded. Staining was validated by measuring klotho mRNA levels,
      using quantitative RT-PCR, in 18 of the samples. RESULTS: Klotho expression was
      high in all endocervical and exocervical normal tissues adjacent to tumour. No
      expression of klotho was noted in 7 out of 38 (18.4%) ADC samples and in 2 out of
      44 (4.5%) SQCC samples. Staining intensity, number of positively stained cells
      and combined intensity score were all lower in tumours compared with normal
      adjacent tissues in ADC and SQCC. Klotho mRNA levels highly correlated with
      immunohistochemical (IHC) staining (p=0.008). CONCLUSIONS: We found reduced
      klotho expression in cervical carcinoma, especially in ADC, compared with normal
      adjacent tissue. Our results support the role of klotho as a potential tumour
      suppressor in cervical cancer. Further studies are required in order to establish
      the therapeutic role of klotho in cervical carcinoma and identify patients who
      may benefit from it.

PMID- 26209730
TI  - Second harmonic generation microscopy is a novel technique for differential
      diagnosis of breast fibroepithelial lesions.
AB  - Breast fibroepithelial lesions, including fibroadenomas and phyllodes tumours,
      are commonly encountered in clinical practice. As histological differences
      between these two related entities may be subtle, resulting in a challenging
      differential diagnosis, pathological techniques to assist the differential
      diagnosis of these two entities are of high interest. An accurate diagnosis at
      biopsy is important given corresponding implications for clinical decision-making
      including surgical extent and monitoring. Second harmonic generation (SHG)
      microscopy is a recently developed optical imaging technique capable of robust,
      powerful and unbiased label-free direct detection of collagen fibril structure in
      tissue without the use of antibodies. We constructed tissue microarrays emulating
      limited materials on biopsy to investigate quantitative collagen signal in
      fibroepithelial lesions using SHG microscopy. Archived formalin-fixed paraffin
      embedded materials of 47 fibroepithelial lesions (14 fibroadenomas and 33
      phyllodes tumours) were evaluated. Higher collagen signal on SHG microscopy was
      observed in fibroadenomas than phyllodes tumours on SHG imaging (p<0.001, area
      under the curve 0.859). At an automated threshold (2.5 million positive pixels),
      the sensitivity and specificity of the SHG microscopy for fibroadenoma
      classification was 71.4% and 84.4%, respectively. To corroborate these findings,
      we performed immunohistochemistry on tissue array sections using collagen I and
      III primary antibodies. Both collagen I and III immunohistochemical expressions
      were also significantly higher in fibroadenomas than in phyllodes tumours
      (p<0.001). In conclusion, label-free collagen quantitation on SHG microscopy is a
      novel imaging approach that can aid the differential diagnosis of fibroepithelial
      lesions. 

PMID- 26209731
TI  - Diagnosis and treatment of early renal disease in patients with type 2 diabetes
      mellitus: what are the clinical needs?
AB  - Renal disease is prevalent in patients with diabetes mellitus type 2. Aggressive
      metabolic control and lowering of systemic and/or intraglomerular blood pressure
      are effective interventions but not without side effects. Thus a better, early
      identification of patients at risk for incidence or progression to end-stage
      renal failure by the use of new, validated biomarkers is highly desirable. In the
      majority of patients, hypertension and hyperglycaemia are pathogenetically
      important pathways for the progression of renal disease. Nonetheless even
      aggressive therapy targeting these factors does not eliminate the risk of end
      stage renal failure and experimental evidence suggests that many other pathways
      (e.g. tubulointerstitial hypoxia or inflammation etc.) also contribute. As their
      individual importance might vary from patient to patient, interventions which
      interfere are likely not to be therapeutically effective in all subjects. In this
      situation, an option to preserve the statistical power of clinical trials is to
      rely on biomarkers that reflect individual pathophysiology. In current clinical
      practice, albuminuria is the biomarker that has been best evaluated to guide
      stratified/personalized therapy but there is a clear need to expand our
      diagnostic abilities. 

PMID- 26209732
TI  - Drugs meeting the molecular basis of diabetic kidney disease: bridging from
      molecular mechanism to personalized medicine.
AB  - Diabetic kidney disease (DKD) is a complex, multifactorial disease and is
      associated with a high risk of renal and cardiovascular morbidity and mortality.
      Clinical practice guidelines for diabetes recommend essentially identical
      treatments for all patients without taking into account how the individual
      responds to the instituted therapy. Yet, individuals vary widely in how they
      respond to medications and therefore optimal therapy differs between individuals.
      Understanding the underlying molecular mechanisms of variability in drug response
      will help tailor optimal therapy. Polymorphisms in genes related to drug
      pharmacokinetics have been used to explore mechanisms of response variability in
      DKD, but with limited success. The complex interaction between genetic make-up
      and environmental factors on the abundance of proteins and metabolites renders
      pharmacogenomics alone insufficient to fully capture response variability. A
      complementary approach is to attribute drug response variability to individual
      variability in underlying molecular mechanisms involved in the progression of
      disease. The interplay of different processes (e.g. inflammation, fibrosis,
      angiogenesis, oxidative stress) appears to drive disease progression, but the
      individual contribution of each process varies. Drugs at the other hand address
      specific targets and thereby interfere in certain disease-associated processes.
      At this level, biomarkers may help to gain insight into which specific
      pathophysiological processes are involved in an individual followed by a rational
      assessment whether a specific drug's mode of action indeed targets the relevant
      process at hand. This article describes the conceptual background and data-driven
      workflow developed by the SysKid consortium aimed at improving characterization
      of the molecular mechanisms underlying DKD at the interference of the molecular
      impact of individual drugs in order to tailor optimal therapy to individual
      patients. 

PMID- 26209733
TI  - Prediction of prevalence of chronic kidney disease in diabetic patients in
      countries of the European Union up to 2025.
AB  - BACKGROUND: Diabetes and chronic kidney disease (CKD) are a growing burden for
      health-care systems. The prevalence of diabetes has increased constantly during
      the last decade, although a slight flattening of end-stage renal disease as a
      result of diabetes has been observed recently in some European countries. In this
      study, we project the prevalence of CKD in patients with diabetes in European
      countries up to the year 2025. METHODS: We analysed the population with diabetes
      and development of nephropathy in 12 European countries, which we computed from
      models published previously and on data from the annual reports of the European
      Renal Association (1998-2011). The prevalence of CKD stage 5 in patients with
      diabetes up to the year 2025 was projected by the Lee-Carter algorithm. Those for
      stage 3 and 4 were then estimated by applying the same ratios of CKD prevalences
      as estimated in the Austrian population with diabetic nephropathy. RESULTS: The
      estimated prevalence of CKD in patients with diabetes is expected to increase in
      all 12 countries up to the year 2025. For CKD stage 3, we estimate for Austria in
      2025 a prevalence of 215 000 per million diabetic population (p.m.p.) (95%
      confidence interval 169 000, 275 000), for CKD4 18 600 p.m.p. (14 500, 23 700)
      and for CKD5 6900 p.m.p. (5400, 8900). The median prevalence in the considered
      countries is 132 900 p.m.p. (IQR: 118 500, 195 800), 11 500 (10 200, 16 900) and
      4300 (3800, 6300) for CKD stages 3, 4 and 5, respectively. Altogether, these data
      predict in the years 2012-25 an annual increase of 3.2% in the prevalence of
      diabetic CKD stage 5. CONCLUSIONS: Due to the increase in prevalence of diabetes
      and CKD5, the costs of renal therapy are expected to rise. We believe that these
      data may help health-care policy makers to make informed decisions.

PMID- 26209734
TI  - Molecular disease presentation in diabetic nephropathy.
AB  - Diabetic nephropathy, as the most prevalent chronic disease of the kidney, has
      also become the primary cause of end-stage renal disease with the incidence of
      kidney disease in type 2 diabetics continuously rising. As with most chronic
      diseases, the pathophysiology is multifactorial with a number of deregulated
      molecular processes contributing to disease manifestation and progression.
      Current therapy mainly involves interfering in the renin-angiotensin-aldosterone
      system using angiotensin-converting enzyme inhibitors or angiotensin-receptor
      blockers. Better understanding of molecular processes deregulated in the early
      stages and progression of disease hold the key for development of novel
      therapeutics addressing this complex disease. With the advent of high-throughput
      omics technologies, researchers set out to systematically study the disease on a
      molecular level. Results of the first omics studies were mainly focused on
      reporting the highest deregulated molecules between diseased and healthy subjects
      with recent attempts to integrate findings of multiple studies on the level of
      molecular pathways and processes. In this review, we will outline key omics
      studies on the genome, transcriptome, proteome and metabolome level in the
      context of DN. We will also provide concepts on how to integrate findings of
      these individual studies (i) on the level of functional processes using the gene
      ontology vocabulary, (ii) on the level of molecular pathways and (iii) on the
      level of phenotype molecular models constructed based on protein-protein
      interaction data. 

PMID- 26209735
TI  - Genome-wide studies to identify risk factors for kidney disease with a focus on
      patients with diabetes.
AB  - Chronic kidney disease (CKD) affects 10-13% of the general population and
      diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD).
      In addition to known demographic, biochemical and lifestyle risk factors,
      genetics is also contributing to CKD risk. In recent years, genome-wide
      association studies (GWAS) have provided a hypothesis-free approach to identify
      common genetic variants that could account for the genetic risk component of
      common diseases such as CKD. The identification of these variants might reveal
      the biological processes underlying renal impairment and could aid in improving
      risk estimates for CKD. This review aims to describe the methods as well as
      strengths and limitations of GWAS in CKD and to summarize the findings of recent
      GWAS in DN. Several loci and SNPs have been found to be associated with distinct
      CKD traits such as eGFR and albuminuria. For diabetic kidney disease, several
      loci were identified in different populations. Subsequent functional studies
      provided insights into the mechanism of action of some of these variants, such as
      UMOD or CERS2. However, overall, the results were ambiguous, and a few of the
      variants were not consistently replicated. In addition, the slow progression from
      albuminuria to ESRD could limit the power of longitudinal studies. The typically
      small effect size associated with genetic variants as well as the small portion
      of the variability of the phenotype explained by these variants limits the
      utility of genetic variants in improving risk prediction. Nevertheless,
      identifying these variants could give a deeper understanding of the molecular
      pathways underlying CKD, which in turn, could potentially lead to the development
      of new diagnostic and therapeutic tools. 

PMID- 26209736
TI  - RNA expression signatures and posttranscriptional regulation in diabetic
      nephropathy.
AB  - In the last decade, the integration of molecular approaches including
      transcriptome and miRNome analyses uncovered pathological mechanisms involved in
      the progression of diabetic nephropathy (DN). Using these techniques, molecular
      marker candidates [both messenger RNA (mRNA) and miRNA] have also been identified
      which may enable the characterization of patients at high risk for progression to
      end-stage renal disease. The results of such studies are urgently needed for a
      molecular definition of DN and for targeted treatment to improve patient care.
      The heterogeneity of kidney tissue and the minute amounts of RNA isolated from
      renal biopsies remain a challenge for omics-studies. Nevertheless, several
      studies have succeeded in the identification of RNA expression signatures in
      patients with diabetes and kidney disease. These studies show a reduced
      expression of growth factors such as VEGF and EGF, and an increased expression of
      matrix components and matrix-modulating enzymes, an activation of specific NF
      kappaB modules, inflammatory pathways and the complement system. microRNAs are
      involved in the fine-tuning of mRNA abundance by binding to the 3' untranslated
      region of a target mRNA, which leads in most cases to translational repression or
      mRNA cleavage and a decrease in protein output. Here, we review the platforms
      used for miRNA expression profiling and ways to predict miRNA targets and
      functions. Several miRNAs have been shown to be involved in the pathogenesis of
      DN (e.g. miR-21, miR-192, miR-215, miR-216a, miR-29, let-7, miR-25, miR-93,
      etc.). Functional studies provide evidence that miRNAs are not only diagnostic
      tools but also represent potential therapeutic targets in DN. 

PMID- 26209737
TI  - Body fluid peptide and protein signatures in diabetic kidney diseases.
AB  - Body fluid protein-based biomarkers carry the hope of improving patient
      management in diabetes by enabling more accurate and earlier detection of
      diabetic kidney disease (DKD), but also of defining the most suitable therapeutic
      targets. We present the data on some of the best studied individual protein
      markers in body fluids and conclude that their potential in clinical application
      for assessing DKD is moderate. Proteome-based approaches aiming at the
      identification of panels of body fluid biomarkers might be a valid alternative.
      We discuss the past (first) clinical proteomics studies in DKD, stressing their
      drawbacks but also the lessons that could be learned from them, as well as the
      more recent studies that have a potential for actual clinical implementation. We
      also highlight relevant issues and current problems associated with clinical
      proteomics from discovery towards application, and give suggestions for solutions
      that may help guiding proteomic studies, thereby removing some of the current
      hurdles for implementation of potentially beneficial results. 

PMID- 26209738
TI  - Key pathways in renal disease progression of experimental diabetes.
AB  - Diabetic nephropathy (DN) is one of the major microvascular complications of
      diabetes mellitus and the leading cause of end-stage kidney disease. Both
      diabetes and chronic kidney disease are risk factors for cardiovascular disease,
      and diabetic patients with renal involvement are three times more likely to
      eventually die of cardiovascular disease than diabetic patients without signs of
      renal failure. In type 2 diabetes, microalbuminuria is a marker of renal
      dysfunction and a crucial predictor of cardiovascular disease. Inhibitors of
      angiotensin II synthesis/activity, while preventing micro- or macroalbuminuria,
      also reduced cardiovascular events in diabetic patients. However, the
      effectiveness of renin angiotensin system blocking agents depends on the time
      when treatment is started, and imperfect renoprotection may occur if therapy
      begins at an advanced disease phase. This raises the need to identify novel
      multidrug approaches that simultaneously inhibit additional pathways other than
      angiotensin II for those diabetic patients who remain at high risk of both poor
      renal and cardiovascular outcomes. Studies in animal models of diabetes have
      contributed to defining relevant cellular mechanisms underlying the pathogenesis
      of DN that could represent possible targets for therapies. The pathogenesis of DN
      is multifactorial, involving a complex series of molecular processes. In this
      review, we report evidence obtained in experimental models of DN on some specific
      processes and pathways implicated in DN that may be crucial for managing this
      disease. 

PMID- 26209740
TI  - New developments concerning the proximal tubule in diabetic nephropathy: in vitro
      models and mechanisms.
AB  - The incidence of Type 2 diabetes is increasing rapidly worldwide, and
      understanding the mechanisms of its complications including diabetic nephropathy
      (DN) is important in the discovery of early biomarkers, understanding the
      causative mechanisms of its complications and identifying therapeutic targets. DN
      is characterized by glomerulosclerosis, tubulointerstitial fibrosis and tubular
      atrophy. The tubular component of the disease is important in progression of
      disease. In vitro models are a valuable alternative to animal studies and an
      effective way to explore mechanisms of human disease. Several proximal tubular
      cell lines have been used in studying mechanisms of DN. Key extracellular
      conditions that contribute to damage to the proximal tubule in DN include
      hyperglycaemia, proteinuria, and hypoxia and inflammation. According to current
      knowledge, these exert their effects through changes in transforming growth
      factor beta signalling, the renin-angiotensin system, dysregulation of pathways
      such as the polyol pathway, hexosamine pathway and protein kinase C pathway and
      through formation of advanced glycation end products. Studies in cell culture
      models have been instrumental in the delineation of these processes. However, all
      of the existing cell culture models have limitations including dedifferentiation.
      To bring research forward along with technological advances, such as major
      advances in 'omics' methodologies, a more suitable model is necessary. The
      RPTEC/TERT1 cell line is a promising alternative to previous proximal tubular
      epithelial cell lines due to features that resemble the cell type in vivo, such
      as its epithelial characteristics, maintenance of functional capabilities,
      glucose handling, expression of the primary cilium and transport activity
      including albumin. This cell line will facilitate identification of mechanisms of
      DN with potential to identify new therapeutic targets. 

PMID- 26209741
TI  - Chances and challenges of using routine data collections for renal health care
      research.
AB  - BACKGROUND: Collections of electronic medical records (EMRs) can provide a rich
      source of information for renal health care research. However, their use in
      statistical analyses requires many preparatory steps, including coding of
      freetext entries and clear definitions of time windows for harvesting prognostic
      factors and outcomes. We analyse a large collection of EMRs to identify
      prognostic factors of adequate health care in diabetic patients at risk for
      chronic kidney disease, and discuss benefits and risks of such re-use of routine
      data. METHODS: In a representative sample of 695 068 patient records collected in
      58 Austrian general practitioners' offices, we could identify 31 374 patients
      with diabetes mellitus. As outcomes, we investigated whether a patient received a
      serum creatinine measurement, and the time elapsing between two consecutive serum
      creatinine measurements. Prognostic factors were defined by extracting previous
      diagnoses, laboratory measurements, drug prescriptions and demographic
      characteristics from the records. RESULTS: Serum creatinine was measured annually
      in 44.4% of diabetic patients with previous signs of reduced kidney function and
      in 20.5% of the patients without such signs. Within 1 year after the first
      measurement, a follow-up measurement was made in 79.4 and 68.4% of the patients,
      respectively. Previous diagnoses, laboratory measurements, drug prescriptions and
      demographic characteristics explained 41% of the observed variance of kidney
      function monitoring. With 24% explained variance, previous referrals to
      laboratories were identified as the most important prognostic factor group.
      CONCLUSIONS: The analysis of large routine data collections poses various
      challenges, among which the need for coding free text into variables and various
      sources of biases are most demanding. However, routine data collections represent
      the daily practice of health care and offer many chances for renal health
      services and outcomes research.

PMID- 26209739
TI  - Methodology used in studies reporting chronic kidney disease prevalence: a
      systematic literature review.
AB  - BACKGROUND: Many publications report the prevalence of chronic kidney disease
      (CKD) in the general population. Comparisons across studies are hampered as CKD
      prevalence estimations are influenced by study population characteristics and
      laboratory methods. METHODS: For this systematic review, two researchers
      independently searched PubMed, MEDLINE and EMBASE to identify all original
      research articles that were published between 1 January 2003 and 1 November 2014
      reporting the prevalence of CKD in the European adult general population. Data on
      study methodology and reporting of CKD prevalence results were independently
      extracted by two researchers. RESULTS: We identified 82 eligible publications and
      included 48 publications of individual studies for the data extraction. There was
      considerable variation in population sample selection. The majority of studies
      did not report the sampling frame used, and the response ranged from 10 to 87%.
      With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas
      13% used the enzymatic assay for creatinine determination. Isotope dilution mass
      spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%)
      equations were most often used to estimate glomerular filtration rate (GFR). CKD
      was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies.
      Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was
      reported by sex and age strata in 54 and 50% of the studies, respectively. In
      publications with a primary objective of reporting CKD prevalence, 39% reported a
      95% confidence interval. CONCLUSIONS: The findings from this systematic review
      showed considerable variation in methods for sampling the general population and
      assessment of kidney function across studies reporting CKD prevalence. These
      results are utilized to provide recommendations to help optimize both the design
      and the reporting of future CKD prevalence studies, which will enhance
      comparability of study results.

PMID- 26209742
TI  - Dietary risk factors for incidence or progression of chronic kidney disease in
      individuals with type 2 diabetes in the European Union.
AB  - BACKGROUND: Although the prevalence of chronic kidney disease (CKD) is ~ 30% in
      the group of people with diabetes, data on interventions in the very early stage
      of the disease are still missing. Furthermore, the effects of modifiable
      lifestyle factors such as nutrition on incidence and progression of CKD in
      patients with diabetes in Europe remain elusive. METHODS: We analyzed whether
      diet quality and adherence to dietary guidelines using the modified Alternate
      Healthy Eating Index (mAHEI) score was associated with CKD incidence or
      progression after 5.5 years in 3088 European participants of the ONgoing
      Telmisartan Alone and in combination with Ramipril Global Endpoint Trial
      (ONTARGET) with type 2 diabetes and baseline normo- or micro-albuminuria. Death
      was considered as a competing risk in the multinomial logit regression models,
      which were adjusted for age, gender, duration of diabetes, ONTARGET
      randomization, baseline albuminuria and glomerular filtration rate (GFR). We also
      estimated the potential impact on population health of improvement in diet
      quality. RESULTS: At study end, 450 (14.6%) participants had died and 926 (30%)
      had experienced the renal endpoint of incidence or progression of CKD, of which
      422 (13.7%) participants had progressed to micro- or macro-albuminuria, 596
      (19.3%) had a GFR-decline of >5% per year and 18 (0.6%) had developed end-stage
      renal disease. Participants in the healthiest tertile of the mAHEI score had a
      decreased risk of incidence or progression of CKD (odds ratio 0.8, 95% confidence
      interval 0.68-0.94) and death (0.65, 0.52-0.81) compared with participants in the
      least healthy tertile. If individuals with a suboptimal dietary quality (e.g.
      mAHEI < 28) were able to improve their diet to an mAHEI of 28, 3.2% of CKD
      incidence or progression and 10.0% of deaths might be avoided in 5.5 years.
      CONCLUSIONS: If the association between diet and these endpoints is causal, then
      optimizing diet quality in individuals with diabetes who have no CKD or very
      early CKD would have substantial population benefits in terms of prevention of
      CKD incidence or progression and mortality in this high-risk population.

PMID- 26209743
TI  - Prognostic clinical and molecular biomarkers of renal disease in type 2 diabetes.
AB  - Diabetic kidney disease occurs in ~ 25-40% of patients with type 2 diabetes.
      Given the high risk of progressive renal function loss and end-stage renal
      disease, early identification of patients with a renal risk is important. Novel
      biomarkers may aid in improving renal risk stratification. In this review, we
      first focus on the classical panel of albuminuria and estimated glomerular
      filtration rate as the primary clinical predictors of renal disease and then move
      our attention to novel biomarkers, primarily concentrating on assay-based
      multiple/panel biomarkers, proteomics biomarkers and metabolomics biomarkers. We
      focus on multiple biomarker panels since the molecular processes of renal disease
      progression in type 2 diabetes are heterogeneous, rendering it unlikely that a
      single biomarker significantly adds to clinical risk prediction. A limited number
      of prospective studies of multiple biomarkers address the predictive performance
      of novel biomarker panels in addition to the classical panel in type 2 diabetes.
      However, the prospective studies conducted so far have small sample sizes, are
      insufficiently powered and lack external validation. Adequately sized validation
      studies of multiple biomarker panels are thus required. There is also a paucity
      of studies that assess the effect of treatments on novel biomarker panels and
      determine whether initial treatment-induced changes in novel biomarkers predict
      changes in long-term renal outcomes. Such studies can not only improve our
      healthcare but also our understanding of the mechanisms of actions of existing
      and novel drugs and may yield biomarkers that can be used to monitor drug
      response. We conclude that this will be an area to focus research on in the
      future.

PMID- 26209744
TI  - Will the future lie in multitude? A critical appraisal of biomarker panel studies
      on prediction of diabetic kidney disease progression.
AB  - Diabetic kidney disease is diagnosed and staged by albuminuria and estimated
      glomerular filtration rate. Although albuminuria has strong predictive power for
      renal function decline, there is still variability in the rate of renal disease
      progression across individuals that are not fully captured by the level of
      albuminuria. Therefore, research focuses on discovering and validating additional
      biomarkers that improve risk stratification for future renal function decline and
      end-stage renal disease in patients with diabetes, on top of established
      biomarkers. Most studies address the value of single biomarkers to predict
      progressive renal disease and aim to understand the mechanisms that underlie
      accelerated renal function decline. Since diabetic kidney disease is a disease
      encompassing several pathophysiological processes, a combination of biomarkers
      may be more likely to improve risk prediction than a single biomarker. In this
      review, we provide an overview of studies on the use of multiple biomarkers and
      biomarker panels, appraise their study design, discuss methodological pitfalls
      and make recommendations for future biomarker panel studies. 

PMID- 26209745
TI  - Foetal programming and cortisol secretion in early childhood: A meta-analysis of
      different programming variables.
AB  - It is widely recognized that different events may take place in the intrauterine
      environment that may influence later developmental outcome. Scholars have long
      postulated that maternal prenatal stress, alcohol or drug use, and cigarette
      smoking may impact foetal formation of the hypothalamus-pituitary-adrenal (HPA)
      axis, which may later influence different aspects of early childhood
      socioemotional and cognitive development. However, results linking each of these
      factors with child cortisol secretion have been mixed. The current meta-analysis
      examined the relation between each of these programming variables and child
      cortisol secretion in studies conducted up to December 31st, 2012. Studies were
      included if they were conducted prior to child age 60 months, and if they
      reported an index of effect size linking either maternal prenatal stress, alcohol
      or drug use, or cigarette smoking with an index of child cortisol secretion. In
      total, 19 studies (N=2260) revealed an average effect size of d=.36 (p<.001).
      Moderator analyses revealed that greater effect sizes could be traced to maternal
      alcohol use, to the use of retrospective research methodology, where mothers are
      questioned after childbirth regarding programming variables, and to the use of
      baseline measures of cortisol secretion, as opposed to recovery measures.
      Discussion focuses on processes that link the environment to foetal development
      and how both are linked to later adaptation. 

PMID- 26209746
TI  - Everyday listeners' impressions of speech produced by individuals with adductor
      spasmodic dysphonia.
AB  - Individuals with adductor spasmodic dysphonia (ADSD) have reported that
      unfamiliar communication partners appear to judge them as sneaky, nervous or not
      intelligent, apparently based on the quality of their speech; however, there is
      minimal research into the actual everyday perspective of listening to ADSD
      speech. The purpose of this study was to investigate the impressions of listeners
      hearing ADSD speech for the first time using a mixed-methods design. Everyday
      listeners were interviewed following sessions in which they made ratings of ADSD
      speech. A semi-structured interview approach was used and data were analyzed
      using thematic content analysis. Three major themes emerged: (1) everyday
      listeners make judgments about speakers with ADSD; (2) ADSD speech does not sound
      normal to everyday listeners; and (3) rating overall severity is difficult for
      everyday listeners. Participants described ADSD speech similarly to existing
      literature; however, some listeners inaccurately extrapolated speaker attributes
      based solely on speech samples. Listeners may draw erroneous conclusions about
      individuals with ADSD and these biases may affect the communicative success of
      these individuals. Results have implications for counseling individuals with
      ADSD, as well as the need for education and awareness about ADSD. 

PMID- 26209748
TI  - Early decline in functional ovarian reserve in young women with low (CGGn < 26)
      FMR1 gene alleles.
AB  - Mouse fmr1 models, and recent cross-sectional human data, suggest that different
      triple CGGn ranges of the fragile X mental retardation 1 (FMR1) gene are
      associated with variations in ovarian aging and infertility treatment outcomes.
      The FMR1 mutation affecting reproductive function most negatively in humans is
      the so-called low mutation, characterized by CGGn < 26. We here present a first
      longitudinal study of selected young women with normal functional ovarian reserve
      (FOR). In a prospective cohort study, we selected among 233 young oocyte donors
      (mean age 24.8 +/- 3.3 years) as study population of 66 who had more than 1 anti
      Mullerian hormone (AMH) level drawn over a 4-year period. AMH curves, as
      reflection of FOR, were then statistically compared between women with and
      without low FMR1 alleles. Biallelic low FMR1 (hom-low/low) donors already at
      initial presentation demonstrated significantly lower FOR than donors with
      biallelic normal (norm) FMR1 (CGGn = 26-34; P = 0.001). Although monoallelic low
      FMR1 at initial presentation was not yet associated with decreased FOR, it over 4
      years did demonstrate significantly enhanced declines in FOR (P = 0.046).
      Including repeat measurements, low/low (P = 0.006) and high/high (CGGn > 34)
      alleles (P < 0.001) demonstrated lower FOR by AMH than norm donors. Even
      monoallelic low FMR1 alleles are, thus, already at young female ages associated
      with accelerated declines in FOR. Low FMR1 alleles, therefore, potentially
      represent a screening tool for women at genetic risk toward premature ovarian
      senescence, representing in all races circa 10% of the female population.

PMID- 26209747
TI  - Significant differences in fecal microbiota are associated with various stages of
      glucose tolerance in African American male veterans.
AB  - The importance of gut microbiota in pathogenesis of diabetes remains unknown.
      This study investigated the relationship between microbiota and metabolic markers
      in African American men (AAM) with prediabetes and hypovitaminosis D. The study
      was ancillary to a randomized trial of vitamin D supplementation with weekly
      ergocalciferol (50,000 IU) conducted in AAM veterans over 12 months (D
      Intervention in Veterans Affairs). Glycemic groups (Gr) were characterized based
      on changes in oral glucose tolerance between baseline and exit. Subjects with
      stable normal glucose tolerance were assigned to Gr-1 and those with stable
      prediabetes (impaired glucose tolerance and impaired fasting glucose) to Gr-2.
      Microbiota composition was analyzed in stool collected at the exit (n = 115) and
      compared between Gr-1 and Gr-2, as well as between the lowest and highest
      quartiles of dietary intake of energy and fat, hemoglobin A1c, and serum 25
      hydroxyvitamin D (25[OH]D) level. Differences between Gr-1 and Gr-2 included the
      Bacteroidetes/Firmicutes and Bacteroidales/Clostridia ratios and differences in
      genera such as Ruminococcus and Dialister. Changes in specific taxa associated
      with the lowest and highest quartiles of 25(OH)D (eg, Ruminococcus, Roseburia,
      Blautia, Dorea) were clearly distinct from those of dietary intake (eg,
      Bacteroides, Bacteroides/Prevotella ratio) or A1c (eg, Faecalibacterium,
      Catenibacterium, Streptococcus). These findings suggest a novel interaction
      between microbiota and vitamin D and a role for microbiota in early stages of
      diabetes development. Although results suggest that specific taxa are associated
      with glycemic stability over time, a causative relationship between microbiota
      makeup and dysglycemia is still to be demonstrated. 

PMID- 26209749
TI  - Tumor-infiltrating lymphocytes, forkhead box P3, programmed death ligand-1, and
      cytotoxic T lymphocyte-associated antigen-4 expressions before and after
      neoadjuvant chemoradiation in rectal cancer.
AB  - Preclinical studies have suggested that cytotoxic agents and radiation may partly
      deliver their antitumor activities by activating antitumor immune response.
      However, the alterations of tumor immune microenvironment including
      immunosuppressive molecules during chemoradiotherapy and their associations with
      clinical features and prognosis in rectal cancer have not been thoroughly
      investigated. Therefore, we investigate the densities of cluster of
      differentiation 8 (CD8) positive tumor-infiltrating lymphocytes (TILs), CD4+TILs,
      natural killer cell (NK)-TILs, myeloid-derived suppressor cells (MDSCs),
      transcription factor forkhead box P3 (FOXP3)+TILs, programmed death ligand-1 (PD
      L1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) before and after
      neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients to determine their
      predictive and prognostic effects. We screen 62 rectal cancer patients who
      underwent nCRT followed by radical surgery. Pretreatment biopsy specimens and
      posttreatment surgically resected specimens of all patients are retrieved to
      perform the immunohistochemistry of CD8, CD4, CD56, FOXP3, CD33, CD11b, PD-L1,
      and CTLA-4. The CD8+TILs and CD4+TILs in post-nCRT resected specimens are
      significantly higher than that in pre-nCRT biopsy specimens (P = 0.004 and 0.005,
      respectively). Expressions of MDSC, FOXP3+TILs, and CTLA-4 are relative stable
      after nCRT. Tumors with high density of CD8+TILs, CD4+TILs, and low MDSC-TILs are
      more sensitive to nCRT (P = 0.022, 0.022 and 0.005, respectively). High
      pretreatment CD8+TILs are associated with better disease-free survival and
      overall survival (P = 0.016 and 0.022, respectively). NK-TILs are detected only
      in 6 of 62 rectal cancer specimens evaluated. Cell surface PD-L1 positive by
      tumor cells (1 of 62) and stroma cells (3 of 62) are very low. We may conclude
      that tumor immunity is activated after nCRT by increased infiltrating CD8+ and
      CD4+ T cells and relative stable numbers MDSC-TILs, FOXP3+TILs, and coinhibitory
      molecules. Pre-nCRT CD8+TILs, CD4+TILs, and MDSC-TILs are sensitive predictive
      marker for response to CRT, and high CD8+TILs are associated with better
      prognosis.

PMID- 26209750
TI  - BDNF Val66Met polymorphism and plasma levels in Chinese Han population with
      obsessive-compulsive disorder and generalized anxiety disorder.
AB  - BACKGROUND: Anxiety disorders are a category of mental disorders characterized by
      feelings of anxiety and fear, which include generalized anxiety disorder (GAD).
      Obsessive-Compulsive Disorder (OCD) used to be categorized as anxiety disorder in
      DSM-IV. However OCD was no longer included in anxiety disorders and came into its
      own category titled as Obsessive-Compulsive and Related Disorders (OCRD) in DSM
      5. It will be interesting to explore is there any different biological
      characteristics between OCD and anxiety disorders. Brain-derived neurotrophic
      factor (BDNF) was a potential candidate gene in both OCD and GAD. The results of
      genetic association studies between BDNF and OCD have been inconsistent. BDNF
      plasma/serum levels in OCD have been found lower than those in healthy controls.
      However the heritable reason of the lowered BDNF levels was not well elucidated.
      The amount of studies about BDNF and GAD were relatively small. The aims of this
      study were to determine whether single nucleotide polymorphism Val66Met of BDNF
      was associated with OCD and GAD, to examine BDNF plasma levels in OCD and GAD,
      and to explore whether Val66Met variation influences BDNF plasma levels. METHODS:
      We genotyped Val66Met variation in 148 OCD patients, 108 GAD patients and 99
      healthy controls. Within the same sample, BDNF plasma levels were determined in
      113 OCD patients, 102 GAD patients and 63 healthy controls. RESULTS: Val66Met
      variation was not associated with OCD or GAD. BDNF plasma levels in OCD and GAD
      patients were significant lower than those in healthy controls. Val66Met
      variation had no influence on BDNF plasma levels. No difference was found between
      OCD and GAD. Results do not change no matter taking OCD and GAD as one group or
      separated two. LIMITATIONS: First, the sample size for genotyping was relatively
      small, which leaded to a low statistical power of the genetic part in this study.
      Second, we genotyped just one SNP in BDNF gene. Third, parts of the participants
      did not be assayed for BDNF plasma levels. CONCLUSIONS: Our findings support the
      hypothesis that BDNF is involved in the pathophysiology of mental disorders, not
      only OCD but also GAD. OCD and GAD patients both show lower BDNF plasma levels
      compared to healthy controls. The BDNF plasma levels are not associated with
      Val66Met variation.

PMID- 26209751
TI  - The histone acetyltransferase PsGcn5 mediates oxidative stress responses and is
      required for full virulence of Phytophthora sojae.
AB  - In eukaryotic organisms, histone acetyltransferase complexes are coactivators
      that are important for transcriptional activation by modifying chromatin. In this
      study, a gene (PsGcn5) from Phytophthora sojae encoding a histone
      acetyltransferase was identified as a homolog of one component of the histone
      acetyltransferase complex from yeasts to mammals. PsGcn5 was constitutively
      expressed in each stage tested, but had a slightly higher expression in
      sporulating hyphae and 3 h after infection. PsGcn5-silenced mutants were
      generated using polyethylene glycol-mediated protoplast stable transformation.
      These mutants had normal development, but compared to wild type strains they had
      higher sensitivity to hydrogen peroxide (H2O2) and significantly reduced
      virulence in soybean. Diaminobenzidine staining revealed an accumulation of H2O2
      around the infection sites of PsGcn5-silenced mutants but not for wild type
      strains. Inhibition of the plant NADPH oxidase by diphenyleneiodonium prevented
      host-derived H2O2 accumulation in soybean cells and restored infectious hyphal
      growth of the mutants. Thus, we concluded that PsGcn5 is important for growth
      under conditions of oxidative stress and contributes to the full virulence of P.
      sojae by suppressing the host-derived reactive oxygen species.

PMID- 26209752
TI  - Volatile squalene from a nonseed plant Selaginella moellendorffii: Emission and
      biosynthesis.
AB  - The triterpene squalene is a key metabolic intermediate for sterols, hopanoids
      and various other triterpenoids. The biosynthesis of squalene is catalyzed by
      squalene synthase (SQS), which converts two molecules of farnesyl diphosphate to
      squalene. In this study, a lycophyte Selaginella moellendorffii was found to emit
      squalene as a volatile compound under a number of conditions that mimic biotic
      stresses. Searching the genome sequence of S. moellendorffii led to the
      identification of a putative squalene synthase gene. It was designated as SmSQS.
      SmSQS is homologous to known squalene synthases from other plants and animals at
      both the amino acid level and structural level. Recombinant SmSQS expressed in
      Escherichia coli catalyzed the formation of squalene using farnesyl diphosphate
      as substrate. The expression of SmSQS was significantly induced by the same set
      of stress factors that induced the emission of volatile squalene from S.
      moellendorffii plants. Taken together, these results support that SmSQS is
      responsible for the biosynthesis of volatile squalene and volatile squalene may
      have a role in the defense of S. moellendorffii plants against biotic stresses. 

PMID- 26209753
TI  - Lamotrigine induced DIHS/DRESS: Manifestations, treatment, and outcome in 57
      patients.
AB  - OBJECTIVE: To evaluate the clinical features, course, response to treatment, and
      outcome of lamotrigine induced drug-induced hypersensitivity syndrome (DIHS) or
      drug reaction with eosinophilia and systemic symptoms (DRESS). METHODS: A
      comprehensive PubMed and Scopus search (covering the period from January 1999
      through April 2014) of the English and non-English literature (with English
      abstract) was conducted to identify published reports of severe cutaneous adverse
      reactions (SCARs) associated with lamotrigine therapy. RESULTS: This study
      population included 57 patients, of whom 38 (66.67%) were female and 19 (33.33%)
      were male. The latency period varied from 9 days to 120 days, with a mean of
      27.58 +/- 20.65 days. Multisystem involvement was present in 97.37% (37/38)
      patients. Systemic corticosteroids were administered to (61.29%) 19/31 patients.
      35/38 (92.11%) patients recovered completely, one patient developed liver failure
      and needed liver transplant, one died from septic shock and one died from
      multiple organ failure. CONCLUSIONS: We found a greater predominance of women
      with LTG-DIHS/DRESS, and 68.42% patients were >18 years of age. The presenting
      symptoms in most of patients were fever, skin rash, liver involvement,
      hypereosinophilia, and lymphadenopathy. Lamotrigine is associated to a rather
      high risk of severe cutaneous adverse reactions and to the risk of dying from
      such reactions, likes many other anticonvulsants. Early recognition and
      withdrawal of the suspected agent may avoid irreversible damage to the organs
      will be life saving.

PMID- 26209754
TI  - Gluten chorea.

PMID- 26209755
TI  - Achalasia with megaesophagus and tracheal compression in a young patient: A case
      report.
AB  - INTRODUCTION: Achalasia is one of the most common causes of dysphagia. Typical
      symptoms include difficulties in controlling the swallowing process,
      regurgitation, weight loss, and chest pain. A megaesophagus rarely causes
      tracheal compression with consecutive acute dyspnea or similar respiratory
      symptoms. PRESENTATION OF CASE: A 23-year-old male patient presented with
      difficulties in swallowing, a consecutive massive weight loss over the past three
      years, and minor respiratory ailments. Further diagnostics revealed a
      megaesophagus caused by achalasia leading to a severe compression of the trachea.
      A laparoscopic Heller myotomy with anterior semi-fundoplication 180 degrees 
      according to Dor was performed. DISCUSSION: Acute dyspnea and similar respiratory
      symptoms are rarely observed in patients with achalasia, especially in young
      patients. Early diagnosis and timely, proper treatment are the hallmarks of
      restoring esophageal and tracheobronchial function and of successful prevention
      of severe long-lasting complications of the disease. When not treated properly,
      the disease may have progressed rapidly, leading to distinct respiratory symptoms
      such as stridor and acute dyspnea CONCLUSION: This report emphasizes that
      physicians should be alert and consider airway obstruction and signs of dyspnea
      as severe and threatening symptoms in extensive cases of achalasia with
      megaesophagus. Early surgical treatment provides a therapeutic option to obviate
      the occurrence of acute respiratory distress and consecutive complications. In
      particular, difficulties in intubation prior to surgery must be considered.

PMID- 26209756
TI  - Papillary fibroelastoma of the anterior leaflet of the mitral valve mimicking
      vegetation.
AB  - INTRODUCTION: The papillary fibroelastoma (PFE) is a rare and benign primary
      cardiac tumor, and the mostly frequently found tumor occurring in cardiac valves.
      CASE PRESENTATION: We describe a 52 year old female presenting a history of 2
      weeks of fever due to wound infection after breast's surgery. A preoperative
      echocardiography demonstrated a mass >1cm(2) originating from the anterior
      leaflet of the mitral valve mimicking vegetation. The patient underwent
      successful surgical removal of the PFE. The histologic evaluation demonstrated a
      PFE. DISCUSSION: With the introduction of echocardiography, the diagnosis of
      these tumors in living patients has been reported sporadically. PFE have been
      found most often on valve leaflets, chordae tendineae, and both ventricles. The
      differential diagnosis of PFE includes other cardiac tumors, thrombus,
      vegetation, and Lambl's excrescences. CONCLUSION: To summarize, we report a PFE
      of the anterior leaflet of the mitral valve. The diagnosis was confirmed by
      histopathological examination after surgical removal. Finally, careful
      echocardiographic analyses during evaluation of valvular masses are strongly
      recommended for differential diagnosis.

PMID- 26209757
TI  - Primary solitary lymphoma of the fourth ventricle.
AB  - INTRODUCTION: Primary central nervous lymphoma(PCNSL) is a rare form of non
      Hodgkin lymphoma confined to the central nervous system. Most of the lesions are
      supratentorial and periventricular, often involving deep structures such as
      corpus callosum and basal ganglion. Isolated intraventricular lymphoma is rare
      and only a few case reports. We report, to the best of our knowledge, the seventh
      case of isolated PCNSL in the fourth ventricle in an immunocompetent patient.
      PRESENTATION OF CASE: A 61-year-old male presenting with 3 months of headache and
      dizziness followed with unsteady gait for days. The MR imaging of brain revealed
      a homogeneously enhancing lesion occupying almost the whole 4th ventricle.The
      tumor was removed subtotally via suboccipital craniotomy. Histopathology revealed
      the lesion be a diffuse large B-cell lymphoma. DISCUSSION: PCNSL is an important
      consideration in the differential diagnosis of intracranial mass lesion. The
      unusual location in surgically accessible fourth ventricle in posterior fossa,
      the isolation of the tumor may present a compelling indication for surgical
      resection. CONCLUSION: We suggest that primary lymphoma should be considered with
      homogenous lesions of the 4th ventricle. Also aggressive surgical resection in
      this surgically accessible location, instead of biopsy only, is rational.

PMID- 26209759
TI  - Mechanisms of fibrinogen adsorption at the silica substrate determined by QCM-D
      measurements.
AB  - Adsorption kinetics of fibrinogen at a silica substrate was thoroughly studied in
      situ using the QCM-D method. Because of low dissipation, the Sauerbrey's equation
      was used for calculating the wet mass per unit area (wet coverage of the
      protein). Measurements were done for various bulk suspension concentrations, flow
      rates and pHs. These experimental data were compared with the theoretical dry
      coverage data derived from the solution of the mass transfer equation. In this
      way, the hydration functions and water factors of fibrinogen monolayers were
      quantitatively evaluated for various pHs. In the case of pH 7.4 and ionic
      strength of 0.15 M, the hydration function changed from 0.75 to 0.6 for the dry
      coverage Gamma(d) equal to 0 and 4 mg m(-2), respectively. Interestingly, for pH
      7.4 and 4.5 (ionic strength of 10(-2) M) a minimum of the hydration function
      appeared at Gamma(d) ca. 2 mg m(-2). Analytical polynomial expressions were
      formulated for the interpolation of the experimental results. By using the
      hydration functions, the fibrinogen adsorption/desorption runs derived from QCM-D
      measurements were converted to the Gamma(d) vs. the time relationships. This
      allowed to precisely determine the maximum coverage that varied between 1.2 mg m(
      2) at pH 3.5 and 4.2 mg m(-2) at pH 7.4 for ionic strength of 0.15 M. These
      results agree with theoretical modeling and previous experimental data derived by
      using ellipsometry, OWLS and TIRF. Various fibrinogen adsorption mechanisms were
      revealed by exploiting the maximum coverage data whose validity was also
      confirmed by the dissipation vs. the dry mass relationships. Beside significance
      to basic science, these results enable to develop a robust technique, based on
      the QCM-D measurements, suitable for precisely determining the dry mass of
      protein monolayers adsorbed under various physicochemical conditions.

PMID- 26209758
TI  - A case of a colocutaneous fistula: A rare complication of mesh migration into the
      sigmoid colon after open tension-free hernia repair.
AB  - INTRODUCTION: The Lichtenstein technique is commonly used in inguinal hernia
      repair and a polypropylene mesh is the most frequently used mesh. Mesh migration
      into the colon has been rarely reported in the literature. Here we report a case
      of a colocutaneous fistula that developed following delayed mesh migration into
      the sigmoid colon. PRESENTATION OF CASE: A 52-year-old man undergone Lichtenstein
      repair for left direct inguinal herniain 2008. Three years later, he presented
      complaining of rectal bleeding and concurrent bloody discharge from the hernia
      repair scar. Colonoscopy identified an internal fistulous orifice with
      intraluminal extrusion of the polypropylene mesh. Furthermore, abdominal
      ultrasound revealed a fistulous tract extending from the sigmoid colon to the
      anterior abdominal wall, and a fistulogram confirmed the findings. Open
      sigmoidectomy and resection of the abdominal wall with the fistula tract was
      performed, and BIO-A((r)) tissue reinforcement meshwas placed. His postoperative
      course was unremarkable and was discharged on postoperative day 3. DISCUSSION:
      Mesh migration after mesh inguinal hernia repair is unpredictable. A previous
      report has presented complications related to prosthetics in hernia repair, such
      as infection, contraction, rejection, and, rarely, mesh migration.Mesh migration
      may occur as an early or late complication after hernioplasty. CONCLUSION: During
      hernia repair, the surgeon should carefully check for a sliding hernia, which may
      contain the sigmoid colon within the sac, because failure to identify this hernia
      may lead to direct contact between the mesh and the colon, which may cause
      pressure necrosis and fistula formation followed by mesh migration.

PMID- 26209760
TI  - Performance evaluation for three pollution detection methods using data from a
      real contamination accident.
AB  - Early warning systems have been widely deployed to safeguard water security. Many
      contamination detection methods have been developed and evaluated in the past
      decades. Although encouraging detection performance has been obtained and
      reported, these evaluations mainly used artificial or laboratory data. The
      evaluation of detection performance with data from real contamination accidents
      has rarely been conducted. Implementation of contamination event methods without
      full assessment using field data might lead to failure of an early warning
      system. In this paper, the detection performance of three contamination detection
      methods, a Pearson correlation Euclidean distance (PE) based detection method, a
      multivariate Euclidean distance (MED) method and a linear prediction filter (LPF)
      method, was evaluated using data from a real contamination accident. Results
      improve understanding of the implementation of detection methods to field
      situations and show that all methods are prone to yielding worse detection
      performance when applied to data from a real contamination accident. They also
      revealed that the Pearson correlation Euclidean distance based method is more
      capable of differentiating between equipment noise and presence of contamination
      and has greater potential to be used in real field situations than the MED and
      LPF methods. 

PMID- 26209761
TI  - Dynamic modeling the composting process of the mixture of poultry manure and
      wheat straw.
AB  - Due to lack of understanding of the complex nature of the composting process,
      there is a need to provide a valuable tool that can help to improve the
      prediction of the process performance but also its optimization. Therefore, the
      main objective of this study is to develop a comprehensive mathematical model of
      the composting process based on microbial kinetics. The model incorporates two
      different microbial populations that metabolize the organic matter in two
      different substrates. The model was validated by comparison of the model and
      experimental data obtained from the composting process of the mixture of poultry
      manure and wheat straw. Comparison of simulation results and experimental data
      for five dynamic state variables (organic matter conversion, oxygen
      concentration, carbon dioxide concentration, substrate temperature and moisture
      content) showed that the model has very good predictions of the process
      performance. According to simulation results, the optimum values for air flow
      rate and ambient air temperature are 0.43 l min(-1) kg(-1)OM and 28  degrees C,
      respectively. On the basis of sensitivity analysis, the maximum organic matter
      conversion is the most sensitive among the three objective functions. Among the
      twelve examined parameters, MUmax,1 is the most influencing parameter and X1 is
      the least influencing parameter. 

PMID- 26209762
TI  - Recovering organic matters and ions from wastewater by genetically engineered
      Bacillus subtilis biomass.
AB  - Water pollution causes substantial damage to the environment and to human health,
      and the current methods to treat pollution suffer from high cost and low
      efficiency, resulting in increased environmental damages. Using genetic
      modification and functional selection, we developed a novel biosorbent from
      Genetically Engineered Bacillus subtilis (GEBS) cells. At a ratio of biosorbent
      to direct blue dye of about 1:1.25 in a water solution, the dye pigments can be
      completely adsorbed in 40 s, decreasing COD to zero. Contrary to other
      biosorbents, ions such as Fe(2+) and Cu(2+) have significant advantages in terms
      of the adsorbing efficiency. The GEBS biomass can therefore capture both organics
      and ions from wastewater simultaneously and achieve co-precipitation in 2-10 min,
      which are features critical for practical applications of wastewater treatment.
      In addition, we used six different eluting solutions to regenerate used biomass,
      all resulting in renewed, highly efficient color and COD elimination capacities,
      with the best elution solution being NaHCO3 and Na2CO3. For practical
      applications, we showed a high COD elimination rate when using the GEBS biomass
      to treat raw water from textile enterprises, paper mill, and petrochemical
      industries. Compared with currently available adsorbing agents, the GEBS cells
      can adsorb organic and ion waste much faster and with much higher efficiency, can
      be regenerated and recycled efficiently, and may have broad applications in
      treating organic water pollution. 

PMID- 26209763
TI  - Tetra-allelic SNPs: Informative forensic markers compiled from public whole
      genome sequence data.
AB  - Multiple-allele single nucleotide polymorphisms (SNPs) are potentially useful for
      forensic DNA analysis as they can provide more discrimination power than normal
      binary SNPs. In addition, the presence in a profile of more than two alleles per
      marker provides a clearer indication of mixed DNA than assessments of imbalanced
      signals in the peak pairs of binary SNPs. Using the 1000 Genomes Phase III human
      variant data release of 2014 as the starting point, this study collated 961 tetra
      allelic SNPs that pass minimum sequence quality thresholds and where four
      separate nucleotide substitution alleles were detected. Although most of these
      loci had three of the four alleles in combined frequencies of 2% or less, 160 had
      high heterozygosities with 50 exceeding those of 'ideal' 0.5:0.5 binary SNPs.
      From this set of most polymorphic tetra-allelic SNPs, we identified markers most
      informative for forensic purposes and explored these loci in detail. Subsets of
      the most polymorphic tetra-allelic SNPs will make useful additions to current
      panels of forensic identification SNPs and ancestry-informative SNPs. The 24 most
      discriminatory tetra-allelic SNPs were estimated to detect more than two alleles
      in at least one marker per profile in 99.9% of mixtures of African contributors.
      In European contributor mixtures 99.4% of profiles would show multiple allele
      patterns, but this drops to 92.6% of East Asian contributor mixtures due to
      reduced levels of polymorphism for the 24 SNPs in this population group. 

PMID- 26209764
TI  - Triggering of myocardial infarction by increased ambient fine particle
      concentration: Effect modification by source direction.
AB  - BACKGROUND: Previously, we reported a 18% increased odds of ST-elevation
      myocardial infarction (STEMI) associated with each 7.1 ug/m(3) increase in PM2.5
      concentration in the hour prior to MI onset. We found no association with non-ST
      elevation myocardial infarction (NSTEMI). We examined if this association was
      modified by PM2.5 source direction. METHODS: We used the NOAA HYbrid Single
      Particle Lagrangian Trajectory (HYSPLIT) model to calculate each hourly air mass
      location for the 24 hours before each case or control time period in our previous
      PM2.5/STEMI case-crossover analysis. Using these data on patients with STEMI
      (n=338), hourly PM2.5 concentrations, and case-crossover methods, we evaluated
      whether our PM2.5/STEMI association was modified by whether the air mass passed
      through each of the 8 cardinal wind direction sectors in the previous 24h.
      RESULTS: When the air mass passed through the West-Southwest direction (WSW) any
      time in the past 24h, the odds of STEMI associated with each 7.1ug/m(3) increase
      in PM2.5 concentration in the previous hour (OR=1.27; 95% CI=1.08, 1.22) was
      statistically significantly (p=0.01) greater than the relative odds of STEMI
      associated with increased PM2.5 concentration when the wind arrived from any
      other direction (OR=0.99; 95% CI=0.80, 1.22). We found no other effect
      modification by any other source direction. Further, relative odds estimates were
      largest when the time spent in the WSW was 8-16 h, compared to <=7 h or 17-24 h,
      suggesting that particles arising from sources in this direction were more potent
      in triggering STEMIs. CONCLUSIONS: Since relative odds estimates were higher when
      the air mass passed through the WSW octant in the past 24h, there may be specific
      components of the ambient aerosol that are more potent in triggering STEMIs. This
      direction is associated with substantial emissions from coal-fired power plants
      and other industrial sources of the Ohio River Valley, many of which are
      undergoing modifications to reduce their emissions.

PMID- 26209765
TI  - Geometric rules of channel gating inferred from computational models of the P2X
      receptor transmembrane domain.
AB  - The P2X receptors are trimeric ATP-gated ion channels and mediate chemical
      communication between eukaryotic cells. Each P2X subunit contains two
      transmembrane helices, M1 and M2, and the M2 helix packs around an ion conduction
      pore. Here, I have reconstructed the three-dimensional models of the zebrafish
      P2X4 transmembrane domain using spatial restraints on helical packing. The models
      are stable in lipid bilayers during molecular dynamics simulation and adopt
      different conformations depending on bilayer hydrophobic thickness. Comparison of
      these conformations shows that the pore-lining residues L340, A344 and A347 each
      have multiple packing sites that define the pore configurations. Shift of L340
      packing between different sites alters the side-chain orientation that occludes
      the pore or removes this occlusion. L340, A344 and A347 also gate the pore by
      expansion-contraction mechanism based on their packing patterns. Finally, pore
      expansions at the L340 and A344 levels are mutually exclusive, so the P2X gating
      may involve sequential pore opening at L340 and A344 levels to allow ion
      conduction. In summary, the current study shows that the computational assembly
      of the helical membrane protein is not only possible, but also necessary to
      provide insights into the mechanisms of channel gating. 

PMID- 26209766
TI  - pi-Stacking effects on the hydrogen bonding capacity of methyl 2-naphthoate.
AB  - pi-stacking effects of fused two-ring system of methyl 2-naphthoate (MNP) with
      benzene derivatives on the CO group, as a hydrogen bond acceptor, has been
      investigated by the quantum mechanical calculations at the M06-2X/6-311++G(d,p)
      level of theory. All substituents enhance the stacking interactions relative to
      the unsubstituted case, where enhancement is higher for electron-withdrawing
      substituents (EWSs). The hydrogen bonding ability of lone pairs of O* atom of
      stacked MNP decreases in the presence of strong electron-withdrawing substituents
      (NO2, NO and CN). The hydrogen bond ability of CO group of MNP is related to the
      sum of local minima of electrostatic potentials (?ESPs) observed between stacked
      rings. The charge transfer (CT) is lower in the presence of EWSs. The study also
      shows that the interaction energies (DeltaE) are linearly dependent on the
      combination of the sum of electron densities calculated at the bond critical
      points (BCPs) between the rings (?rhoBCP) and the sum of electron charge
      densities calculated at the ring critical points (?rhoRCP). There are good
      relationships between the Hammett constant sigmameta and the global minimum of
      electrostatic potential around the O* atom (Vmin), the sum of local minima of the
      electrostatic potentials obtained between stacked rings, and the results of
      natural population analysis (NPA). An excellent correlation was found between the
      DeltaE values and a combination of the electrostatic (sigmameta),
      resonance/induction (sigmapara) and dispersion/polarizibility (molar
      refractivity, MR) substituent constant terms. 

PMID- 26209767
TI  - A quantitative LC-MS/MS method for determining ipragliflozin, a sodium-glucose co
      transporter 2 (SGLT-2) inhibitor, and its application to a pharmacokinetic study
      in rats.
AB  - Ipragliflozin is a highly potent and selective sodium-dependent glucose co
      transporter-2 (SGLT2) inhibitor, a novel class of hypoglycemic agents. The aim of
      the present study was to establish a new highly sensitive and rapid liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative
      analysis of ipragliflozin in rat plasma and apply this method to a
      pharmacokinetic study in rats. Empagliflozin was used as an internal standard
      (I.S.) and liquid-liquid extraction was conducted using tert-butyl methyl ether.
      Chromatographic separation was accomplished on a Quicksorb ODS (2.1mm i.d.*150mm,
      5MUm in size) with acetonitrile/0.1% formic acid (90:10, v/v) at a flow rate of
      0.2mL/min. An API 3200 triple quadrupole mass spectrometer operating in the
      positive electrospray ionization mode with multiple reaction monitoring was used
      to detect ipragliflozin and I.S. transitions: m/z 422.0 [M+NH4](+)->151.0 for
      ipragliflozin and m/z 451.2 [M+H](+)->71.0 for I.S. Inter- and intra-day
      accuracies and precisions were within +/-15%. This validated method was
      successfully applied to a pharmacokinetic study of ipragliflozin in rats. This
      assay method may contribute to assessment of novel SGLT2 inhibitors using the rat
      as an animal model. 

PMID- 26209768
TI  - Challenges and solutions in the bioanalysis of BMS-986094 and its metabolites
      including a highly polar, active nucleoside triphosphate in plasma and tissues
      using LC-MS/MS.
AB  - BMS-986094, a nucleotide polymerase inhibitor of the hepatitis C virus, was
      withdrawn from clinical trials because of a serious safety issue. To investigate
      a potential association between drug/metabolite exposure and toxicity in
      evaluations conducted after the termination of the BMS-986094 development
      program, it was essential to determine the levels of BMS-986094 and its major
      metabolites INX-08032, INX-08144 and INX-09054 in circulation and the active
      nucleoside triphosphate INX-09114 in target and non-target tissues. However,
      there were many challenges in the bioanalysis of these compounds. The
      chromatography challenge for the extremely polar nucleoside triphosphate was
      solved by applying mixed-mode chromatography which combined anion exchange and
      reversed-phase interactions. The LC conditions provided adequate retention and
      good peak shape of the analyte and showed good robustness. A strategy using
      simultaneous extraction but separate LC analysis of the prodrug BMS-986094 and
      its major circulating metabolites was used to overcome a carryover issue of the
      hydrophobic prodrug while still achieving good chromatography of the polar
      metabolites. In addition, the nucleotide analytes were not stable in the presence
      of endogenous enzymes. Low pH and low temperature were required for blood
      collection and plasma sample processing. However, the use of phosphatase
      inhibitor and immediate homogenization and extraction were critical for the
      quantitative analysis of the active triphosphate, INX-09114, in tissue samples.
      To alleviate the bioanalytical complexity caused by multiple analytes, different
      matrices, and various species, a fit-for-purpose approach to assay validation was
      implemented based on the needs of drug safety assessment in non-clinical (GLP or
      non-GLP) studies. The assay for INX-08032 was fully validated in plasma of
      toxicology species. The lower limit of quantification was 1.00ng/mL and the
      linear curve range was 1.00-500.00ng/mL using a weighted (1/x(2)) linear
      regression model. Intra-assay and inter-assay precision (CV, %) ranged from 2.3%
      to 5.5% and accuracy within +/-2.2% from nominal. INX-08032 was found to be
      stable in acidified mouse plasma for at least 24h in wet ice bath, 125 days at 
      70 degrees C and following at least three freeze-thaw cycles. No endogenous
      components in plasma were found to interfere with the measurement. The extraction
      recovery was between 90% and 95%. The assays for BMS-986094, INX-08144, INX-09054
      and INX-09114 were qualified with wider acceptance criteria for accuracy and
      precision. Analyte stability was also evaluated to guide sample collection,
      storage, and processing. These assays were successfully applied to an
      investigative toxicokinetic and tissue metabolite profiling study described in
      the article. 

PMID- 26209769
TI  - An investigation of paper based microfluidic devices for size based separation
      and extraction applications.
AB  - Conventional microfluidic devices are typically complex and expensive. The
      devices require the use of pneumatic control systems or highly precise pumps to
      control the flow in the devices. This work investigates an alternative method
      using paper based microfluidic devices to replace conventional microfluidic
      devices. Size based separation and extraction experiments conducted were able to
      separate free dye from a mixed protein and dye solution. Experimental results
      showed that pure fluorescein isothiocyanate could be separated from a solution of
      mixed fluorescein isothiocyanate and fluorescein isothiocyanate labeled bovine
      serum albumin. The analysis readings obtained from a spectrophotometer clearly
      show that the extracted tartrazine sample did not contain any amount of Blue-BSA,
      because its absorbance value was 0.000 measured at a wavelength of 590nm, which
      correlated to Blue-BSA. These demonstrate that paper based microfluidic devices,
      which are inexpensive and easy to implement, can potentially replace their
      conventional counterparts by the use of simple geometry designs and the capillary
      action. These findings will potentially help in future developments of paper
      based microfluidic devices. 

PMID- 26209770
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      method to determine intact glucosinolates in bee pollen.
AB  - A new method was developed to determine twelve intact-glucosinolates (GLSs)
      (glucoiberin, GIB; glucoraphanin, GRA; glucoerucin GER; gluconapin, GNA;
      glucotropaeolin, GTL; glucobrassicin, GBC; gluconasturtiin, NAS; glucoalyssin,
      ALY; 4-hydroxyglucobrassicin, 4OH; 4-methoxyglucobrassicin, 4ME;
      neoglucobrassicin, NEO; sinigrin, SIN) in bee pollen, by means of liquid
      chromatography tandem mass spectrometry (LC-MS/MS) with electrospray ionization
      (ESI). An efficient extraction procedure was proposed (average analyte recoveries
      were between 85% and 96%); this involved a solid-liquid extraction (SLE) with
      heated water, followed by a solid phase extraction (SPE) with a weak anion
      exchange (NH2) sorbent. Chromatography was performed on a Gemini((r)) C18
      analytical column with a mobile phase of formic acid in water (0.5%,v/v) and
      formic acid in acetonitrile (0.5%,v/v), in gradient elution mode at 1mL/min,
      resulted in baseline-separated peaks and a run time of 30min. The method was
      fully validated in terms of selectivity, limits of detection (LOD) and
      quantification (LOQ), linearity, carry-over effect, reinjection reproducibility,
      precision and accuracy. A good selectivity, low LODs and LOQs, ranging from 1 to
      16MUg/kg, wide linear ranges from LOQ to 1000MUg/kg, and satisfactory reinjection
      reproducibility, precision and accuracy with relative standard deviation and
      relative error values lower than or equal to 9%; meanwhile, results indicates a
      negligible carry-over effect. The proposed method was applied to analyze intact
      GLSs in bee pollen. Nine of the GLSs studied were identified in certain samples
      analyzed over a wide concentration range (LOQ-2226MUg/kg), and significant
      differences in GLS content were observed among the samples. 

PMID- 26209771
TI  - High-throughput screening for new psychoactive substances (NPS) in whole blood by
      DLLME extraction and UHPLC-MS/MS analysis.
AB  - The increasing number of new psychoactive substances (NPS) present in the illicit
      market render their identification in biological fluids/tissues of great concern
      for clinical and forensic toxicology. Analytical methods able to detect the huge
      number of substances that can be used are sought, considering also that many NPS
      are not detected by the standard immunoassays generally used for routine drug
      screening. The aim of this work was to develop a method for the screening of
      different classes of NPS (a total of 78 analytes including cathinones, synthetic
      cannabinoids, phenethylamines, piperazines, ketamine and analogues, benzofurans,
      tryptamines) from blood samples. The simultaneous extraction of analytes was
      performed by Dispersive Liquid/Liquid Microextraction DLLME, a very rapid, cheap
      and efficient extraction technique that employs microliters amounts of organic
      solvents. Analyses were performed by a target Ultrahigh Performance Liquid
      Chromatography tandem Mass Spectrometry (UHPLC-MS/MS) method in multiple reaction
      monitoring (MRM). The method allowed the detection of the studied analytes with
      limits of detection (LODs) ranging from 0.2 to 2ng/mL. The proposed DLLME method
      can be used as an alternative to classical liquid/liquid or solid-phase
      extraction techniques due to its rapidity, necessity to use only microliters
      amounts of organic solvents, cheapness, and to its ability to extract
      simultaneously a huge number of analytes also from different chemical classes.
      The method was then applied to 60 authentic real samples from forensic cases,
      demonstrating its suitability for the screening of a wide number of NPS. 

PMID- 26209772
TI  - The Toddler Language and Motor Questionnaire: A mother-report measure of language
      and motor development.
AB  - This study empirically evaluates the psychometric properties of a new mother
      answered developmental instrument for toddlers, the Toddler Language and Motor
      Questionnaire (TLMQ). Mothers of 1132 15- to 38-month-old children filled out a
      144-item instrument, tapping the toddlers' competences in five language and motor
      subtests. Concurrent validity was investigated in an independent sample by
      administering the McCarthy Scales of Children's Abilities (MSCA) individually to
      47 children and the TLMQ to their mothers. A two-factor solution emerged in
      principal axis factor analyses with a promax rotation, with motor subtests
      loading high on one of the factors and the language subtests on the other.
      Toddlers' genders significantly affected outcome on all of the five subtests.
      Divergent and convergent correlations emerged between the TLMQ's motor composite
      and scales of the MSCA. Partially convergent and divergent correlations emerged
      between the TLMQ's language composite and scales of the MSCA. The findings show
      that young children's motor and language development can be reliably and validly
      assessed by using a psychometrically constructed questionnaire completed by
      mothers. 

PMID- 26209773
TI  - From numeracy to arithmetic: Precursors of arithmetic performance in children
      with cerebral palsy from 6 till 8 years of age.
AB  - Children with cerebral palsy (CP) are generally delayed in arithmetic compared to
      their peers. The development of early numeracy performance in children with CP is
      not yet evident, nor have the factors associated with change over time been
      identified. Therefore, we examined the development of numeracy in children with
      CP over a two year period and studied which cognitive factors were predictive of
      arithmetic performance. A longitudinal study with three measurement waves
      separated by one year was conducted. 56 children participated (37 boys, M=6.0
      years, SD=.58). Standardized tasks were used to assess verbal- and visual-spatial
      working memory, executive functioning, fine motor skills and early numeracy
      performance. In addition, experimental tasks were developed to measure counting
      and arithmetic. The results showed that early numeracy performance of children
      with CP increased between 6 and 8 years of age. Structural equation modelling
      showed that early numeracy was strongly related to arithmetic performance at the
      consecutive year. Working memory, counting and fine motor skills were all
      positively related to early numeracy performance a year later. Furthermore,
      working memory and fine motor skills were precursors of the development of early
      numeracy. Considering the importance of numeracy and arithmetic in daily life and
      in academic and work success, children with CP could substantially benefit from
      intervention programs aimed at increasing working memory and early numeracy
      performance. 

PMID- 26209774
TI  - Identification and quantification of 1,3-dimethylbutylamine (DMBA) from Camellia
      sinensis tea leaves and dietary supplements.
AB  - 1,3-dimethylbutylamine (DMBA), is a CNS stimulant, which has recently been
      identified in multiple dietary supplements and sometimes labeled as a natural
      constituent of Pouchung tea. DMBA is an homologue of 1,3-dimethylamylamine (DMAA)
      which the US Food and Drug Administration has attempted to remove from all
      dietary supplements after DMAA consumption was linked to strokes, heart disease,
      and sudden death. To address questions concerning the natural origin of DMBA,
      three independent analytical methods were developed for analyzing authentic tea
      samples and dietary supplements. A high performance thin layer chromatography
      (HPTLC) method was developed for the fast screening and chemical fingerprint
      analysis. Chiral Gas Chromatography-Mass Spectrometry (GC-MS) was used to
      determine the enantiopurity and a validated Ultra-High Performance Liquid
      Chromatography-Quadrupole Time of Flight Mass Spectrometry (UHPLC-QToF-MS) method
      was developed for the quantification of DMBA. Using these techniques the presence
      of DMBA was confirmed using a reference standard and was not detected in any of
      25 authentic or commercial samples of Camellia sinensis tea leaves (green tea,
      black tea, Oolong tea, and Pouchung tea). Of 13 dietary supplements tested, 11
      contained DMBA in racemic form and ranged from 0.1 to 214mg per daily dose.

PMID- 26209775
TI  - Concurrent delivery of carmustine, irinotecan, and cisplatin to the cerebral
      cavity using biodegradable nanofibers: In vitro and in vivo studies.
AB  - Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor,
      and the prognosis of patients afflicted with GBM has been dismal, exhibiting
      progressive neurologic impairment and imminent death. Even with the most active
      regimens currently available, chemotherapy achieves only modest improvement in
      the overall survival. New chemotherapeutic agents and novel approaches to therapy
      are required for improving clinical outcomes. In this study, we used an
      electrospinning technique and developed biodegradable poly[(d,l)-lactide-co
      glycolide] nanofibrous membranes that facilitated a sustained release of
      carmustine (or bis-chloroethylnitrosourea, BCNU), irinotecan, and cisplatin. An
      elution method and a high-performance liquid chromatography assay were employed
      to characterize the in vitro and in vivo release behaviors of pharmaceuticals
      from the nanofibrous membranes. The experimental results showed that the
      biodegradable, nanofibrous membranes released high concentrations of BCNU,
      irinotecan, and cisplatin for more than 8 weeks in the cerebral cavity of rats. A
      histological examination revealed progressive atrophy of the brain tissues
      without inflammatory reactions. Biodegradable drug-eluting nanofibrous membranes
      may facilitate sustained delivery of various and concurrent chemotherapeutic
      agents in the cerebral cavity, enhancing the therapeutic efficacy of GBM
      treatment and preventing toxic effects resulting from the systemic administration
      of chemotherapeutic agents. 

PMID- 26209776
TI  - Structural effects and nanoparticle size are essential for quantum dots
      metallothionein complex formation.
AB  - Interaction between semiconductor nanocrystals, cadmium telluride quantum dots
      (CdTe QDs) capped with mercaptosuccinic acid (MSA) and metallothionein (MT) was
      investigated. MSA-capped CdTe QDs were synthesized in aqueous solution. Mixture
      of MT and MSA-capped CdTe QDs has been investigated by various analytical methods
      as follows: tris-tricine gel electrophoresis, fluorescence evaluation and
      electrochemical detection of catalysed hydrogen evolution. The obtained results
      demonstrate that MSA-capped CdTe QDs and MT do not create firmly bound stabile
      complex. However, weak electrostatic interactions contribute to the interaction
      of MT with MSA-capped CdTeQDs. It can be concluded that QDs size influences the
      QDs and MT interaction. The smallest QDs had the highest affinity to MT and vice
      versa. 

PMID- 26209777
TI  - Novel pH sensitive ferrogels as new approach in cancer treatment: Effect of the
      magnetic field on swelling and drug delivery.
AB  - Ferrogels (or magnetic hydrogels) are cross-linked polymer networks containing
      magnetic nanoparticles: they are mechanically soft and highly elastic and at the
      same time they exhibit a strong magnetic response. Our work focuses on an
      combinatorial strategy to improve the efficacy of 5-Fluorouracil (5-FU) assisted
      chemotherapy, by developing novel multifunctional pH-sensitive ferrogels. We
      designed gels based on N,N'-dimethylacrylamide monomers polymerized in presence
      of methacrylic acid or 2-aminoethyl methacrylate hydrochloride, containing ferro
      nanoparticles. The influence of polymeric matrix composition and exposition to
      magnetic field (MF) on swelling behavior and drugs release were investigated at
      pH 7.4 and 5. In particular, the magnetic field was obtained by using permanent
      magnetic bar (0.25 T) or electromagnet (0.5 and 1.2 T), with the aim to analyze
      quantitatively the magnetic effects. A strong influence of the magnetic field on
      ferrogels properties have been observed. Swelling analysis indicated a dependence
      on both pH and network composition, reaching a maximum at pH 7.4, for
      formulations containing methacrylic acid, while the application of MF appeared to
      decrease the swelling percentages. Release profiles of 5-FU showed effective
      modulation in release by application of MF: drug release is always higher in the
      presence of a magnetic field and generally increases with its intensity. The
      combining effect of pH sensitive properties and application of MF improved the
      performance of the systems. Results showed that our ferrogels may be
      technologically applicable as devices for delivery of 5-FU in a controllable
      manner.

PMID- 26209778
TI  - Synthesis and characterization of dendro-PLGA nanoconjugate for protein
      stabilization.
AB  - The present investigation was aimed to develop the dendro-PLGA nanoconjugate
      (DPNC) for protection of insulin from degradation as well as its sustained
      release from nano-formulation. DPNC formulation was synthesized by 1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide hydrochloride (EDC) coupling reaction and
      therapeutic efficacy of encapsulated protein (insulin) was measured by Sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Fourier transform
      infrared spectroscopy (FTIR) and circular dichorism (CD) spectroscopy. We have
      also demonstrated the ability of DPNC formulation to prevent the native
      conformation of insulin within the system by comparing the amount of free protein
      with the protein extracted from this system. Stability study further revealed
      that as compared to free protein, DPNC formulation was more efficient to
      stabilize the protein. Additionally, in vivo data of protein loaded system in
      rats showed that DPNC formulation can able to maintain the native structure of
      insulin and hence retain therapeutic efficacy of protein. The novel dendro-PLGA
      nanoconjugate not only stabilize the insulin but also work as sustained release
      reservoir for insulin which reduces the frequency of dosage and side effect
      associate with denatured protein. 

PMID- 26209779
TI  - Gas-generating TPGS-PLGA microspheres loaded with nanoparticles (NIMPS) for co
      delivery of minicircle DNA and anti-tumoral drugs.
AB  - Drug-DNA combination therapies are receiving an ever growing focus due to their
      potential for improving cancer treatment. However, such approaches are still
      limited by the lack of multipurpose delivery systems that encapsulate drugs and
      condense DNA simultaneously. In this study, we describe the successful
      formulation of gas-generating pH-responsive D-alpha-tocopherol PEG succinate
      poly(D,L-lactic-co-glycolic acid) (TPGS-PLGA) hollow microspheres loaded with
      both Doxorubicin (Dox) and minicircle DNA (mcDNA) nanoparticles as a strategy to
      co-deliver these therapeutics. For this study mcDNA vectors were chosen due to
      their increased therapeutic efficiency in comparison to standard plasmid DNA. The
      results demonstrate that TPGS-PLGA microcarriers can encapsulate Dox and chitosan
      nanoparticles completely condense mcDNA. The loading of mcDNA-nanoparticles into
      microspheres was confirmed by 3D confocal microscopy and co-localization
      analysis. The resulting TPGS-PLGA-Dox-mcDNA nanoparticle-in-microsphere hybrid
      carriers exhibit a well-defined spherical shape and neutral surface charge.
      Microcarriers incubation in acidic pH produced a gas-mediated Dox release,
      corroborating the microcarriers stimuli-responsive character. Also, the dual
      loaded TPGS-PLGA particles achieved 5.2-fold higher cellular internalization in
      comparison with non-pegylated microspheres. This increased intracellular
      concentration resulted in a higher cytotoxic effect. Successful transgene
      expression was obtained after nanoparticle-mcDNA co-delivery in the microspheres.
      Overall these findings support the concept of using nanoparticle-microsphere
      multipart systems to achieve efficient co-delivery of various drug-mcDNA
      combinations.

PMID- 26209780
TI  - pH dependence of daunorubicin interactions with model DMPC:Cholesterol membranes.
AB  - Mixed monolayers composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine
      (DMPC):Cholesterol 7:3 prepared by the Langmuir-Blodgett method were used as
      model membranes to investigate the influence of the anticancer drug daunorubicin
      (DNR) on the properties of the lipid membrane. The Langmuir monolayer experiments
      revealed that drug - membrane interactions are pH-dependent. The changes in
      monolayer organization at subphases of pH 7.4 containing daunorubicin visualized
      by Brewster Angle Microscopy showed that in the presence of the drug the typical
      morphology observed for phospholipid layers containing cholesterol was no longer
      seen. It supports the explanation of the mechanism of the drug incorporation into
      the layers in terms of the competition between DNR molecules and cholesterol in
      the layer. Increasing surface pressure with time and increasing value of limiting
      surface pressure with increasing drug concentration in the subphase confirmed
      incorporation of the drug into the membranes. The interactions between the lipid
      monolayer and the drug at pH 5.4 were of electrostatic nature between the
      negative part of the DMPC molecule and positively charged drug, while at pH 7.4
      contribution of interactions of daunorubicin with cholesterol was observed. Large
      differences of the surface-pressure vs. time plots were observed at both pH
      values when the DMPC:Cholesterol monolayer was not well organized yet. The
      voltammograms recorded for DMPC:Cholesterol monolayers transferred from the air
      water interface onto gold electrode confirmed the presence of the drug in the
      lipid layer. Based on the charge of the oxidation-reduction peaks corresponding
      to the redox processes of quinone-hydroquinone group in daunorubicin, the initial
      surface concentration of the drug in the membrane and the drug release profile to
      the solution were evaluated. 

PMID- 26209781
TI  - Potential alternative approaches to xenotransplantation.
AB  - There is an increasing worldwide shortage of organs and cells for transplantation
      in patients with end-stage organ failure or cellular dysfunction. This shortage
      could be resolved by the transplantation of organs or cells from pigs into
      humans. What competing approaches might provide support for the patient with end
      stage organ or cell failure? Four main approaches are receiving increasing
      attention - (i) implantable mechanical devices, although these are currently
      limited almost entirely to devices aimed at supporting or replacing the heart,
      (ii) stem cell technology, at present directed mainly to replace absent or
      failing cells, but which is also fundamental to progress in (iii) tissue
      engineering and regenerative medicine, in which the ultimate aim is to replace an
      entire organ. A final novel potential approach is (iv) blastocyst
      complementation. These potential alternative approaches are briefly reviewed, and
      comments added on their current status and whether they are now (or will soon
      become) realistic alternative therapies to xenotransplantation. 

PMID- 26209782
TI  - Extracorporeal shock wave therapy (ESWT) for the treatment of cellulite--A
      current metaanalysis.
AB  - BACKGROUND: The aim of this metaanalysis was to investigate the effectiveness of
      extracorporeal shock wave therapy (ESWT) in cellulite. METHODS: Electronic
      databases (such as Ovid MEDLINE, Scopus and Ovid) as well as reference lists of
      the available studies were evaluated in June 2015 by two expert examiners.
      Assessment of each study's methodological quality was performed with the help of
      the published quality index tool by Downs and Black. RESULTS: This metanalysis
      included a total of eleven clinical trials on the effects of ESWT on cellulite
      with a total of 297 included females. Among the eleven clinical trials five
      randomized controlled trials on ESWT in cellulite with a total number of 123
      females have been published so far. Both, focused as well as radial ESWT devices
      have been found effective in treating cellulite so far. Typically, one or two
      sessions per week and six to eight sessions overall were studied in the published
      clinical trials. Overall, outcome parameters mainly focused on digital
      standardized photographs, circumference measurements and specific ultrasound
      examinations. Reporting quality showed substantial heterogenity from 22 to 82
      points with a mean of 57 points. DISCUSSION: This metanalysis identified eleven
      published clinical studies on ESWT in cellulite with five randomized-controlled
      trials among them. There is growing evidence that both, radial as well as focused
      ESWT and the combination of both are able to improve the degree of cellulite.
      Typically, six to eight treatments once or twice a week have been studied. Long
      term follow-up data beyond one year are lacking as well as details on potential
      combination therapies in cellulite such as with low level laser therapy (LLLT),
      cryolipolysis and others.

PMID- 26209783
TI  - Post-illumination pupil response after blue light: Reliability of optimized
      melanopsin-based phototransduction assessment.
AB  - Melanopsin-containing retinal ganglion cells have recently been shown highly
      relevant to the non-image forming effects of light, through their direct
      projections on brain circuits that regulate alertness, mood and circadian
      rhythms. A quantitative assessment of functionality of the melanopsin-signaling
      pathway could be highly relevant in order to mechanistically understand
      individual differences in the effects of light on these regulatory systems. We
      here propose and validate a reliable quantification of the melanopsin-dependent
      Post-Illumination Pupil Response (PIPR) after blue light, and evaluated its
      sensitivity to dark adaptation, time of day, body posture, and light exposure
      history. Pupil diameter of the left eye was continuously measured during a series
      of light exposures to the right eye, of which the pupil was dilated using
      tropicamide 0.5%. The light exposure paradigm consisted of the following five
      consecutive blocks of five minutes: baseline dark; monochromatic red light (peak
      wavelength: 630 nm, luminance: 375 cd/m(2)) to maximize the effect of subsequent
      blue light; dark; monochromatic blue light (peak wavelength: 470 nm, luminance:
      375 cd/m(2)); and post-blue dark. PIPR was quantified as the difference between
      baseline dark pupil diameter and post-blue dark pupil diameter (PIPR-mm). In
      addition, a relative PIPR was calculated by dividing PIPR by baseline pupil
      diameter (PIPR-%). In total 54 PIPR assessments were obtained in 25 healthy young
      adults (10 males, mean age +/- SD: 26.9 +/- 4.0 yr). From repeated measurements
      on two consecutive days in 15 of the 25 participants (6 males, mean age +/- SD:
      27.8 +/- 4.3 yrs) test-retest reliability of both PIPR outcome parameters was
      calculated. In the presence of considerable between-subject differences, both
      outcome parameters had very high test-retest reliability: Cronbach's alpha > 0.90
      and Intraclass Correlation Coefficient > 0.85. In 12 of the 25 participants (6
      males, mean age +/- SD: 26.5 +/- 3.6 yr) we examined the potential confounding
      effects of dark adaptation, time of the day (morning vs. afternoon), body posture
      (upright vs. supine position), and 24-h environmental light history on the PIPR
      assessment. Mixed effect regression models were used to analyze these possible
      confounders. A supine position caused larger PIPR-mm (beta = 0.29 mm, SE = 0.10,
      p = 0.01) and PIPR-% (beta = 4.34%, SE = 1.69, p = 0.02), which was due to an
      increase in baseline dark pupil diameter; this finding is of relevance for
      studies requiring a supine posture, as in functional Magnetic Resonance Imaging,
      constant routine protocols, and bed-ridden patients. There were no effects of
      dark adaptation, time of day, and light history. In conclusion, the presented
      method provides a reliable and robust assessment of the PIPR to allow for studies
      on individual differences in melanopsin-based phototransduction and effects of
      interventions. 

PMID- 26209784
TI  - Invasive streptococcal disease: a review for clinicians.
AB  - INTRODUCTION: Streptococci are a genus of Gram-positive bacteria which cause
      diverse human diseases. Many of these species have the potential to cause
      invasive infection resulting from the presence of bacteria in a normally sterile
      site. SOURCES OF DATA: Original articles, reviews and guidelines. AREAS OF
      AGREEMENT: Invasive infection by a streptococcus species usually causes life
      threatening illness. When measured in terms of deaths, disability and cost, these
      infections remain an important threat to health in the UK. Overall they are
      becoming more frequent among the elderly and those with underlying chronic
      illness. New observational evidence has become available to support the use of
      clindamycin and intravenous immunoglobulin in invasive Group A streptococcal
      disease. AREAS OF CONTROVERSY: Few interventions for the treatment and prevention
      of these infections have undergone rigorous evaluation in clinical trials. For
      example, the role of preventative strategies such as screening of pregnant women
      to prevent neonatal invasive Group B streptococcal disease needs to be clarified.
      FUTURE PROSPECTS: Studies of invasive streptococcal disease are challenging to
      undertake, not least because individual hospitals treat relatively few confirmed
      cases. Instead clinicians and scientists must work together to build national and
      international networks with the aim of developing a more complete evidence base
      for the treatment and prevention of these devastating infections.

PMID- 26209785
TI  - Qualitative research in age and ageing: enhancing understanding of ageing, health
      and illness.

PMID- 26209786
TI  - Increase in N-terminal pro-brain natriuretic peptide levels, renal function and
      cardiac disease in the oldest old.
AB  - BACKGROUND: the impact of renal function and its changes and the occurrence of
      cardiovascular events on changes in N-terminal pro-brain natriuretic peptide
      levels (NT-proBNP) is unknown in very old age. OBJECTIVE: to assess whether
      increase in NT-proBNP levels over time is still associated with cardiac disease
      and mortality in very old age, independent of renal function. METHODS: changes in
      NT-proBNP levels between age 85 and 90 years and their associations with incident
      cardiac disease, (cardiovascular) mortality and renal function were assessed in
      252 nonagenarian participants from a population-based sample of the Leiden 85
      plus Study. RESULTS: median NT-proBNP increase over 5 years was 154 pg/ml (inter
      quartile range: 29-549), while in the same period estimated glomerular filtration
      rate (eGFR) decreased by 5.8 ml/min/1.73 m(2) (standard deviation 7.5).
      Participants with increasing NT-proBNP levels more frequently developed heart
      failure and atrial fibrillation (odds ratio 2.79, 95% confidence interval (CI)
      1.11-7.02 and 2.63, 95% CI 1.02-6.79, respectively, adjusted for eGFR at age 85
      and change in eGFR) between age 85 and 90 years. Increasing NT-proBNP levels
      between age 85 and 90 years were associated with an increased cardiovascular
      mortality risk after age 90 years compared with not-increasing NT-proBNP levels
      (hazard ratio 1.62, 95% CI 1.04-2.51, adjusted for eGFR at age 90 years and
      change in eGFR). CONCLUSION: in the oldest old, increase in NT-proBNP is
      associated with incident heart failure and atrial fibrillation and risk for
      cardiovascular mortality, independent of decreasing renal function.

PMID- 26209787
TI  - Pathway analysis supports association of nonsyndromic cryptorchidism with genetic
      loci linked to cytoskeleton-dependent functions.
AB  - STUDY QUESTION: What are the genetic loci that increase susceptibility to
      nonsyndromic cryptorchidism, or undescended testis? SUMMARY ANSWER: A genome-wide
      association study (GWAS) suggests that susceptibility to cryptorchidism is
      heterogeneous, with a subset of suggestive signals linked to cytoskeleton
      dependent functions and syndromic forms of the disease. WHAT IS KNOWN ALREADY:
      Population studies suggest moderate genetic risk of cryptorchidism and possible
      maternal and environmental contributions to risk. Previous candidate gene
      analyses have failed to identify a major associated locus, although variants in
      insulin-like 3 (INSL3), relaxin/insulin-like family peptide receptor 2 (RXFP2)
      and other hormonal pathway genes may increase risk in a small percentage of
      patients. STUDY DESIGN, SIZE, DURATION: This is a case-control GWAS of 844 boys
      with nonsyndromic cryptorchidism and 2718 control subjects without syndromes or
      genital anomalies, all of European ancestry. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: All boys with cryptorchidism were diagnosed and treated by a pediatric
      specialist. In the discovery phase, DNA was extracted from tissue or blood
      samples and genotyping performed using the Illumina HumanHap550 and Human610-Quad
      (Group 1) or OmniExpress (Group 2) platform. We imputed genotypes genome-wide,
      and combined single marker association results in meta-analyses for all cases and
      for secondary subphenotype analyses based on testis position, laterality and age,
      and defined genome-wide significance as P = 7 * 10(-9) to correct for multiple
      testing. Selected markers were genotyped in an independent replication group of
      European cases (n = 298) and controls (n = 324). We used several bioinformatics
      tools to analyze top (P < 10(-5)) and suggestive (P < 10(-3)) signals for
      significant enrichment of signaling pathways, cellular functions and custom gene
      lists after multiple testing correction. MAIN RESULTS AND THE ROLE OF CHANCE: In
      the full analysis, we identified 20 top loci, none reaching genome-wide
      significance, but one passing this threshold in a subphenotype analysis of
      proximal testis position (rs55867206, near SH3PXD2B, odds ratio = 2.2 (95%
      confidence interval 1.7, 2.9), P = 2 * 10(-9)). An additional 127 top loci
      emerged in at least one secondary analysis, particularly of more severe
      phenotypes. Cytoskeleton-dependent molecular and cellular functions were
      prevalent in pathway analysis of suggestive signals, and may implicate loci
      encoding cytoskeletal proteins that participate in androgen receptor signaling.
      Genes linked to human syndromic cryptorchidism, including hypogonadotropic
      hypogonadism, and to hormone-responsive and/or differentially expressed genes in
      normal and cryptorchid rat gubernaculum, were also significantly overrepresented.
      No tested marker showed significant replication in an independent population. The
      results suggest heterogeneous, multilocus and potentially multifactorial
      susceptibility to nonsyndromic cryptorchidism. LIMITATIONS, REASONS FOR CAUTION:
      The present study failed to identify genome-wide significant markers associated
      with cryptorchidism that could be replicated in an independent population, so
      further studies are required to define true positive signals among suggestive
      loci. WIDER IMPLICATIONS OF THE FINDINGS: As the only GWAS to date of
      nonsyndromic cryptorchidism, these data will provide a basis for future efforts
      to understand genetic susceptibility to this common reproductive anomaly and the
      potential for additive risk from environmental exposures. STUDY FUNDING/COMPETING
      INTERESTS: This work was supported by R01HD060769 (the Eunice Kennedy Shriver
      National Institute for Child Health and Human Development (NICHD)), P20RR20173
      (the National Center for Research Resources (NCRR), currently P20GM103464 from
      the National Institute of General Medical Sciences (NIGMS)), an Institute
      Development Fund to the Center for Applied Genomics at The Children's Hospital of
      Philadelphia, and Nemours Biomedical Research. The authors have no competing
      interests to declare.

PMID- 26209789
TI  - Depressive symptoms predict future simple disease activity index scores and
      simple disease activity index remission in a prospective cohort of patients with
      early inflammatory polyarthritis.
AB  - OBJECTIVE: To determine whether depressive symptoms assessed in treated patients
      with early inflammatory polyarthritis (EPA) influence disease activity during
      follow-up. METHODS: Consecutively recruited EPA patients were actively treated to
      remission. Simple disease activity index (SDAI) and Center for Epidemiologic
      Studies Depression Scale (CES-D) scores were calculated at inclusion and up to 42
      months into disease. SDAI scores were log-transformed to compute univariate and
      multivariate linear regressions. Parametric interval-censored Kaplan-Meier and
      survival regressions using Weibull distribution were used to assess time to and
      predictors of SDAI remission. RESULTS: A total of 275 EPA patients were recruited
      at a median of 4 months into disease. In multivariate linear regression models,
      accounting for baseline demographic, clinical, serological and functional
      variables and 12-month inflammation markers, CES-D scores at 12 months into
      disease were correlated (r(2) = 0.14) with subsequent SDAI scores. Patients with
      12-month high CES-D (>=19; suggestive of depression) had a lower proportion of
      SDAI remission (31.3% vs 84.3%; P < 0.001) and reached SDAI remission less
      rapidly [hazard ratio = 0.25 (95% CI 0.12, 0.53); P < 0.001]. CONCLUSION: Each
      follow-up SDAI correlated significantly with 12-month depressive symptoms, a
      median of 7 months after initiation of treatment. CES-D scores suggestive of
      depression at 12 months were strongly correlated with delay and failure to reach
      remission later on. Depressive symptoms in treated EPA patients represent
      important clinical issues with long-term association with disease activity.
      Interventions to alleviate persistent depressive symptoms in treated EPA warrant
      careful evaluation of their potential to improve disease remission rates.

PMID- 26209788
TI  - Urinary bisphenol A concentrations and association with in vitro fertilization
      outcomes among women from a fertility clinic.
AB  - STUDY QUESTION: Are urinary BPA concentrations associated with in vitro
      fertilization (IVF) outcomes among women attending an academic fertility center?
      SUMMARY ANSWER: Urinary BPA concentrations were not associated with adverse
      reproductive and pregnancy outcomes among women from a fertility clinic. WHAT IS
      KNOWN ALREADY: Bisphenol A (BPA), an endocrine disruptor, is detected in the
      urine of most Americans. Although animal studies have demonstrated that BPA
      reduces female fertility through effects on the ovarian follicle and uterus, data
      from human populations are scarce and equivocal. STUDY DESIGN, SIZE AND DURATION:
      This prospective cohort study between 2004 and 2012 at the Massachusetts General
      Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up
      to two urine samples prior to oocyte retrieval (total N = 673).
      PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Study participants were women enrolled
      in the Environment and Reproductive Health (EARTH) Study. Intermediate and
      clinical end-points of IVF treatments were abstracted from electronic medical
      records. We used generalized linear mixed models with random intercepts to
      evaluate the association between urinary BPA concentrations and IVF outcomes
      adjusted by age, race, body mass index, smoking status and infertility diagnosis.
      MAIN RESULTS AND THE ROLE OF CHANCE: The specific gravity-adjusted geometric mean
      of BPA was 1.87 ug/l, which is comparable to that for female participants in the
      National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA
      concentrations were not associated with endometrial wall thickness, peak
      estradiol levels, proportion of high quality embryos or fertilization rates.
      Furthermore, there were no associations between urinary BPA concentrations and
      implantation, clinical pregnancy or live birth rates per initiated cycle or per
      embryo transfer. Although we did not find any associations between urinary BPA
      concentrations and IVF outcomes, the relation between BPA and endometrial wall
      thickness was modified by age. Younger women (<37 years old) had thicker
      endometrial thickness across increasing quartiles of urinary BPA concentrations,
      while older women (>=37 years old) had thinner endometrial thickness across
      increasing quartiles of urinary BPA concentrations. LIMITATIONS, REASONS FOR
      CAUTION: Limitations to this study include a possible misclassification of BPA
      exposure and difficulties in extrapolating the findings to the general
      population. WIDER IMPLICATIONS OF THE FINDINGS: Data on the relation between
      urinary BPA concentrations and reproductive outcomes remain scarce and additional
      research is needed to clarify its role in human reproduction. STUDY
      FUNDING/COMPETING INTERESTS: This work was supported by NIH grants R01ES022955,
      R01ES009718 and R01ES000002 from the National Institute of Environmental Health
      Sciences (NIEHS) and grant T32DK00770316 from the National Institute of Child
      Health and Human Development (NICHD). None of the authors has any conflicts of
      interest to declare. The findings and conclusions in this report are those of the
      authors and do not necessarily represent the official position of the Centers for
      Disease Control and Prevention.

PMID- 26209790
TI  - Cardiorespiratory fitness levels and their association with cardiovascular
      profile in patients with rheumatoid arthritis: a cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to investigate the association of different
      physical fitness levels [assessed by the maximal oxygen uptake (VO2max) test]
      with cardiovascular disease (CVD) risk factors in patients with RA. METHODS: A
      total of 150 RA patients were assessed for cardiorespiratory fitness with a
      VO2max test and, based on this, were split in three groups using the 33rd (18.1
      ml/kg/min) and 66th (22.4 ml/kg/min) centiles. Classical and novel CVD risk
      factors [blood pressure, body fat, insulin resistance, cholesterol,
      triglycerides, high-density lipoprotein (HDL), physical activity, CRP, fibrinogen
      and white cell count], 10-year CVD risk, disease activity (DAS28) and severity
      (HAQ) were assessed in all cases. RESULTS: Mean VO2max for all RA patients was
      20.9 (s.d. 5.7) ml/kg/min. The 10-year CVD risk (P = 0.003), systolic blood
      pressure (P = 0.039), HDL (P = 0.017), insulin resistance and body fat (both at P
      < 0.001), CRP (P = 0.005), white blood cell count (P = 0.015) and fibrinogen (P <
      0.001) were significantly different between the VO2max tertiles favouring the
      group with the higher VO2max levels. In multivariate analyses of variance, VO2max
      was significantly associated with body fat (P < 0.001), HDL (P = 0.007), insulin
      resistance (P < 0.003) and 10-year CVD risk (P < 0.001), even after adjustment
      for DAS28, HAQ and physical activity. CONCLUSION: VO2max levels are alarmingly
      low in RA patients. Higher levels of VO2max are associated with a better
      cardiovascular profile in this population. Future studies need to focus on
      developing effective behavioural interventions to improve cardiorespiratory
      fitness in RA.

PMID- 26209791
TI  - Low-dose Bisphenol A Activates Cyp11a1 Gene Expression and Corticosterone
      Secretion in Adrenal Gland via the JNK Signaling Pathway.
AB  - Certain commonly used compounds that interfere with the functions of the
      endocrine system are classified as endocrine-disrupting chemicals (EDCs).
      Bisphenol A (BPA) is an EDC that is widely used in food containers. BPA levels in
      human sera are commonly observed to be approximately 1-100 nM. Compared with the
      effects of BPA on the gonads, its effects on the adrenal gland are poorly
      understood. To investigate the influence of BPA on steroidogenesis, we examined
      the activity of the steroidogenic gene Cyp11a1 and its regulatory pathways in
      mouse Y1 adrenal cortex cells. Treatment with BPA at < 100 uM did not cause cell
      death. However, increased promoter activity and protein expression of Cyp11a1
      were induced by low doses of BPA (10-1000 nM). Moreover, BPA induced c-Jun
      phosphorylation, and a specific inhibitor of c-Jun N-terminal kinase (JNK)
      significantly suppressed BPA-induced steroidogenesis. Thus, treatment of adrenal
      cells with low doses of BPA activated Cyp11a1 and increased corticosterone
      production through the JNK/c-Jun signaling pathway. Identical results were
      observed in rats after BPA injection. The abnormal induction of hormone synthesis
      by BPA in the adrenal gland might be linked to human metabolic defects and
      neuropsychiatric disorders.

PMID- 26209792
TI  - Health promotion across occupational groups: one size does not fit all.
AB  - BACKGROUND: Although several studies have examined the link between specific
      working conditions and health behaviours, very few have comparatively assessed
      the health behaviours of different occupational groups. AIMS: To compare
      protective and risky health behaviours among police officers, ambulance workers,
      hospital staff (doctors and nurses) and office workers, prompted by the need to
      identify key areas for interventions tailored to the needs of different
      occupational groups. METHODS: A cross-sectional postal survey using the Health
      Behaviours Inventory, assessing health behaviours which are risky (alcohol
      intake, smoking, coffee consumption, fast food meals and painkiller consumption)
      and protective (physical activity, eating breakfast and hours of sleep). RESULTS:
      The sample consisted of 1451 employees. Ambulance workers smoked the most
      cigarettes per day (F (4, 1405) = 8.63, P < 0.01), while doctors consumed twice
      as many fast food meals as any other occupational group (F (4, 1415) = 78.45, P <
      0.01) and had the highest daily caffeine consumption (F (4, 1440) = 11.17, P <
      0.01). Ambulance workers and doctors reported the highest frequency of alcohol
      consumption per week (F (4, 1421) = 10.13, P < 0.01). In regard to protective
      health behaviours, office workers reported the highest number of breakfast meals
      per week (F (4, 1431) = 5.7, P < 0.01) and sleeping hours per night (F (4, 1438)
      = 170.34, P < 0.01), while police officers and ambulance workers exercised more
      frequently (F (4, 1420) = 5.764, P < 0.01). CONCLUSIONS: The results of the study
      highlight key priorities for health promotion for different occupational groups
      which need to be taken into consideration in policy making and developing
      workplace interventions.

PMID- 26209793
TI  - Isocyanate exposure and asthma in the UK vehicle repair industry.
AB  - BACKGROUND: Organic diisocyanates are a common cause of occupational asthma,
      particularly in motor vehicle repair (MVR) workers. The UK Health & Safety
      Laboratory provides screening for urinary hexamethylenediamine (UHDA), a
      biomarker of exposure to 1,6-hexamethylene diisocyanate (HDI). The UK
      Surveillance of Work-related and Occupational Respiratory Disease scheme (SWORD)
      has collected reports of occupational asthma since 1996. AIMS: To compare trends
      in HDI exposure with trends in the incidence of work-related asthma attributed to
      isocyanates or paint spraying in MVR workers reported to SWORD. METHODS: Two
      level regression models were used to estimate trends in UHDA levels and work
      related asthma in MVR workers reported to SWORD. The direction and magnitude of
      the trends were compared descriptively. RESULTS: From 2006 to 2014, there was a
      significant decline in the number of urine samples with detectable levels of UHDA
      (odds ratio = 0.96; 95% confidence intervals 0.94-0.98) and minimal change in
      those over the guidance value (1.03; 1.00-1.06). Over the same period, there was
      a significant decline in all asthma cases attributed to isocyanates or paint
      spraying reported to SWORD (0.90; 0.86-0.94) and a non-significant decline among
      MVR workers (0.94; 0.86-1.02). CONCLUSIONS: The simultaneous decrease in HDI
      exposure and incident cases of asthma reported to SWORD is temporally consistent
      with a reduction in exposure to airborne isocyanate leading to a reduction in
      asthma. Although this is not direct evidence of a causal relationship between the
      two trends, it is suggestive.

PMID- 26209794
TI  - Multiple Chronic Conditions, Resilience, and Workforce Transitions in Later Life:
      A Socio-Ecological Model.
AB  - Purpose of the Study: Despite the growing prevalence of multiple chronic
      conditions (MCC), a problem that disproportionally affects older adults, few
      studies have examined the impact of MCC status on changes in workforce
      participation in later life. Recent research suggests that resilience, the
      ability to recover from adversity, may buffer the negative impact of chronic
      disease. Guided by an adapted socio-ecological risk and resilience conceptual
      model, this study examined the buffering effect of resilience on the relationship
      between individual and contextual risks, including MCC, and workforce transitions
      (i.e., leaving the workforce, working fewer hours, working the same hours, or
      working more hours). Design and Methods: Using the Health and Retirement Study,
      this study pooled a sample of 4,861 older workers aged 51 and older with 2
      consecutive biannual waves of data. Nonnested multinomial logistic regression
      analysis was applied. Results: MCC are related to higher risk of transitioning
      out of the workforce. Resilience buffered the negative effects of MCC on
      workforce engagement and remained independently associated with increased
      probability of working the same or more hours compared with leaving work.
      Implications: MCC are associated with movement out of the paid workforce in later
      life. Despite the challenges MCC impose on older workers, having higher levels of
      resilience may provide the psychological resources needed to sustain work
      engagement in the face of new deficits. These findings suggest that identifying
      ways to bolster resilience may enhance the longevity of productive workforce
      engagement.

PMID- 26209795
TI  - Visitors and Resident Autonomy: Spoken and Unspoken Rules in Assisted Living.
AB  - Purpose of the Study: This article explores resident autonomy in assisted living
      (AL) and the effects that visitors and visiting the AL have on that autonomy. We
      examine formal and informal policies that govern visiting in AL, stakeholders'
      views and enforcement of these policies, and the complex arrangements that
      visiting often entails in everyday life in the setting. Design and Methods: Data
      are drawn from a multiyear ethnographic study of autonomy in AL. Research from
      multiple sites included participant observation, informal and in-depth, open
      ended interviews of various stakeholders, and the writing of field notes.
      Research team biweekly discussions and the Atlas.ti software program facilitated
      coding and analysis of interview transcripts and fieldnotes. Results: Our
      ethnographic data highlight complicated factors related to visitors and visiting
      in AL. We discuss two important aspects of visiting: (a) formal and informal
      policies at each setting; and (b) how resident autonomy is expressed or
      suppressed through rules about visiting in AL. Implications: Our data underscore
      the importance of resident autonomy and quality of care in relation to visitors
      and visiting, especially how this relationship is affected by inconsistent and
      confusing formal and informal visiting policies in AL.

PMID- 26209796
TI  - Chronic Illness and Generativity in Late Life: A Case Study.
AB  - Purpose of the Study: This article presents a narrative-based case study about
      chronic illness and genetic uncertainty and their relationship to generativity
      throughout the life course. Our focus is a woman who experienced vision loss
      early in life and interpreted its impact on her generativity through present-day
      biographical rescripting. Design and Methods: The case we present was chosen from
      the study "Generativity and Lifestyles of Older Women," which explored life
      history, social relations, and forms of generativity in an ethnographic interview
      format with 200 older women. Results: In constructing a present-day identity, the
      informant used shifting and conflicted self-constructions to produce a self-image
      as generative. Three critical themes emerged in understanding her life course:
      (a) retrospective interpretations of autonomy; (b) renegotiating control in the
      present, and (c) generativity across the life course. Implications: This article
      contributes an understanding of childlessness as observed through the lenses of
      chronic illness, autonomy, and generativity. We conclude that a history of
      chronic illness, as it is co-occurring with internal debates about the meaning of
      key life events, may influence older adults' present-day identity. Implications
      for later life care needs are discussed.

PMID- 26209797
TI  - Do Canes or Walkers Make Any Difference? NonUse and Fall Injuries.
AB  - Purpose of the Study: Examine patterns of cane and walker use as related to falls
      and fall injuries. Hypotheses: Among people who fall at home, most do not have an
      assistive device with them when they fall. Nonusers who fall sustain more severe
      injuries. Design and Methods: This was a cross-sectional study using a self
      administered written survey completed by 262 people aged 60 and older who were
      community dwelling, cognitively intact, and current cane/walker users with a
      history of falls. They were recruited through clinical practice sites, churches,
      and senior housing in central Michigan. Outcomes of interest included patterns of
      device use, reasons for nonuse, device use at time of fall, and fall-related
      injuries. Results: Seventy-five percent of respondents who fell were not using
      their device at the time of fall despite stating that canes help prevent falls.
      Reasons for nonuse included believing it was not needed, forgetfulness, the
      device made them feel old, and inaccessibility. Perceived risk was not high
      enough to engage in self-protective behavior. However, nonuse led to a
      significantly higher proportion of falls resulting in surgery than among device
      users. Among respondents requiring surgery, 100% were nonusers. Most respondents
      never received a home safety evaluation (68%) and only 50% received training on
      proper device use. Implications: Providers must place increased emphasis on the
      importance of cane/walker use for injury prevention through patient education to
      promote personal relevance, proper fitting, and training. New strategies are
      needed to improve device acceptability and accessibility.

PMID- 26209798
TI  - Spaced seeds improve k-mer-based metagenomic classification.
AB  - MOTIVATION: Metagenomics is a powerful approach to study genetic content of
      environmental samples, which has been strongly promoted by next-generation
      sequencing technologies. To cope with massive data involved in modern metagenomic
      projects, recent tools rely on the analysis of k-mers shared between the read to
      be classified and sampled reference genomes. RESULTS: Within this general
      framework, we show that spaced seeds provide a significant improvement of
      classification accuracy, as opposed to traditional contiguous k-mers. We support
      this thesis through a series of different computational experiments, including
      simulations of large-scale metagenomic projects.Availability and implementation,
      Supplementary information: Scripts and programs used in this study, as well as
      supplementary material, are available from
      http://github.com/gregorykucherov/spaced-seeds-for-metagenomics. CONTACT:
      gregory.kucherov@univ-mlv.fr.

PMID- 26209799
TI  - Mapping networks of light-dark transition in LOV photoreceptors.
AB  - MOTIVATION: In optogenetics, designing modules of long or short signaling state
      lifetime is necessary for control over precise cellular events. A critical
      parameter for designing artificial or synthetic photoreceptors is the signaling
      state lifetime of photosensor modules. Design and engineering of biologically
      relevant artificial photoreceptors is based on signaling mechanisms
      characteristic of naturally occurring photoreceptors. Therefore identifying
      residues important for light-dark transition is a definite first step towards
      rational design of synthetic photoreceptors. A thorough grasp of detailed
      mechanisms of photo induced signaling process would be immensely helpful in
      understanding the behaviour of organisms. RESULTS: Herein, we introduce the
      technique of differential networks. We identify key biological interactions,
      using light-oxygen-voltage domains of all organisms whose dark and light state
      crystal structures are simultaneously available. Even though structural
      differences between dark and light states are subtle (other than the covalent
      bond formation between flavin chromophore and active site Cysteine), our results
      successfully capture functionally relevant residues and are in complete agreement
      with experimental findings from literature. Additionally, using sequence
      structure alignments, we predict functional significance of interactions found to
      be important from network perspective yet awaiting experimental validation. Our
      approach would not only help in minimizing extensive photo-cycle kinetics
      procedure but is also helpful in providing first-hand information on the
      fundamentals of photo-adaptation and rational design of synthetic photoreceptors
      in optogenetics. CONTACT: devrani.dbs@presiuniv.ac.in or soumen@jcbose.ac.in
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 26209800
TI  - Statistically identifying tumor suppressors and oncogenes from pan-cancer genome
      sequencing data.
AB  - MOTIVATION: Several tools exist to identify cancer driver genes based on somatic
      mutation data. However, these tools do not account for subclasses of cancer
      genes: oncogenes, which undergo gain-of-function events, and tumor suppressor
      genes (TSGs) which undergo loss-of-function. A method which accounts for these
      subclasses could improve performance while also suggesting a mechanism of action
      for new putative cancer genes. RESULTS: We develop a panel of five complementary
      statistical tests and assess their performance against a curated set of 99 HiConf
      cancer genes using a pan-cancer dataset of 1.7 million mutations. We identify
      patient bias as a novel signal for cancer gene discovery, and use it to
      significantly improve detection of oncogenes over existing methods (AUROC =
      0.894). Additionally, our test of truncation event rate separates oncogenes and
      TSGs from one another (AUROC = 0.922). Finally, a random forest integrating the
      five tests further improves performance and identifies new cancer genes,
      including CACNG3, HDAC2, HIST1H1E, NXF1, GPS2 and HLA-DRB1. AVAILABILITY AND
      IMPLEMENTATION: All mutation data, instructions, functions for computing the
      statistics and integrating them, as well as the HiConf gene panel, are available
      at www.github.com/Bose-Lab/Improved-Detection-of-Cancer-Genes. CONTACT:
      rbose@dom.wustl.edu SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 26209801
TI  - The MI bundle: enabling network and structural biology in genome visualization
      tools.
AB  - Prioritization of candidate genes emanating from large-scale screens requires
      integrated analyses at the genomics, molecular, network and structural biology
      levels. We have extended the Integrated Genome Browser (IGB) to facilitate these
      tasks. The graphical user interface greatly simplifies building disease networks
      and zooming in at atomic resolution to identify variations in molecular complexes
      that may affect molecular interactions in the context of genomic data. All
      results are summarized in genome tracks and can be visualized and analyzed at the
      transcript level. AVAILABILITY AND IMPLEMENTATION: The MI Bundle is a plugin for
      the IGB. The plugin, help, video and tutorial are available at
      http://cru.genomics.iit.it/igbmibundle/ and https://github.com/CRUiit/igb-mi
      bundle/wiki. The source code is released under the Apache License, Version 2.
      CONTACT: arnaud.ceol@iit.it SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 26209803
TI  - Parametric imaging and quantitative analysis of the PET amyloid ligand
      [(18)F]flutemetamol.
AB  - OBJECTIVES: The amyloid imaging PET tracer [(18)F]flutemetamol was recently
      approved by regulatory authorities in the US and EU for estimation of beta
      amyloid neuritic plaque density in cognitively impaired patients. While the
      clinical assessment in line with the label is a qualitative visual assessment of
      20 min summation images, the aim of this work was to assess the performance of
      various parametric analysis methods and standardized uptake value ratio (SUVR),
      in comparison with arterial input based compartment modeling. METHODS: The
      cerebellar cortex was used as reference region in the generation of parametric
      images of binding potential (BPND) using multilinear reference tissue methods
      (MRTMo, MRTM, MRTM2), basis function implementations of the simplified reference
      tissue model (here called RPM) and the two-parameter version of SRTM (here called
      RPM2) and reference region based Logan graphical analysis. Regionally averaged
      values of parametric results were compared with the BPND of corresponding regions
      from arterial input compartment modeling. Dynamic PET data were also pre-filtered
      using a 3D Gaussian smoothing of 5mm FWHM and the effect of the filtering on the
      correlation was investigated. In addition, the use of SUVR images was evaluated.
      The accuracy of several kinetic models were also assessed through simulations of
      time-activity curves based on clinical data for low and high binding adding
      different levels of statistical noise representing regions and individual voxels.
      RESULTS: The highest correlation was observed for pre-filtered reference Logan,
      with correction for individual reference region efflux rate constant k2'
      (R(2)=0.98), or using a cohort mean k2' (R(2)=0.97). Pre-processing filtered
      MRTM2, unfiltered SUVR over the scanning window 70-90 min and unfiltered RPM also
      demonstrated high correlations with arterial input compartment modeling (MRTM2
      R(2)=0.97, RPM R(2)=0.96 and SUVR R(2)=0.95) Poorest agreement was seen with MRTM
      without pre-filtering (R(2)=0.68). CONCLUSIONS: Parametric imaging allows for
      quantification without introducing bias due to selection of anatomical regions,
      and thus enables objective statistical voxel-based comparisons of tracer binding.
      Several parametric modeling approaches perform well, especially after Gaussian
      pre-filtering of the dynamic data. However, the semi-quantitative use of SUVR
      between 70 and 90 min has comparable agreement with full kinetic modeling, thus
      supporting its use as a simplified method for quantitative assessment of tracer
      uptake.

PMID- 26209802
TI  - Cortical and subcortical contributions to sequence retrieval: Schematic coding of
      temporal context in the neocortical recollection network.
AB  - Episodic memory entails the ability to remember what happened when. Although the
      available evidence indicates that the hippocampus plays a role in structuring
      serial order information during retrieval of event sequences, information
      processed in the hippocampus must be conveyed to other cortical and subcortical
      areas in order to guide behavior. However, the extent to which other brain
      regions contribute to the temporal organization of episodic memory remains
      unclear. Here, we examined multivoxel activity pattern changes during retrieval
      of learned and random object sequences, focusing on a neocortical "core
      recollection network" that includes the medial prefrontal cortex, retrosplenial
      cortex, and angular gyrus, as well as on striatal areas including the caudate
      nucleus and putamen that have been implicated in processing of sequence
      information. The results demonstrate that regions of the core recollection
      network carry information about temporal positions within object sequences,
      irrespective of object information. This schematic coding of temporal information
      is in contrast to the putamen, which carried information specific to objects in
      learned sequences, and the caudate, which carried information about objects,
      irrespective of sequence context. Our results suggest a role for the cortical
      recollection network in the representation of temporal structure of events during
      episodic retrieval, and highlight the possible mechanisms by which the striatal
      areas may contribute to this process. More broadly, the results indicate that
      temporal sequence retrieval is a useful paradigm for dissecting the contributions
      of specific brain regions to episodic memory. 

PMID- 26209804
TI  - Walk Score and Australian adults' home-based walking for transport.
AB  - The relationships of Walk Score, a publicly-accessible walkability assessment
      tool, with walking for transport to and from home were examined among a large
      representative sample of Australian adults aged 18-64 years (N=16,944). Residents
      in highly and somewhat walkable areas were twice and 1.4 times more likely to
      accumulate 30 min of walking per day compared to those in very car-dependent
      neighborhoods, respectively. Mean duration of walking was also longer for
      participants living in highly and somewhat walkable areas compared to those in
      very car-dependent areas. Walk Score has potential as a widely-applicable tool
      for identifying the walkability of local neighborhoods.

PMID- 26209805
TI  - Cervical lacerations in planned versus labor cerclage removal: a systematic
      review.
AB  - OBJECTIVE: The aim of this study was to evaluate the incidence of cervical
      lacerations with cerclage removal planned before labor compared to after the
      onset of labor by a systematic review of published studies. STUDY DESIGN:
      Searches were performed in electronic databases from inception of each database
      to November 2014. We identified all studies reporting the rate of cervical
      lacerations and the timing of cerclage removal (either before or after the onset
      of labor). The primary outcome was the incidence of spontaneous and clinically
      significant intrapartum cervical lacerations (i.e. lacerations requiring
      suturing). RESULTS: Six studies, which met the inclusion criteria, were included
      in the analysis. The overall incidence of cervical lacerations was 8.9% (32/359).
      There were 23/280 (6.4%) cervical lacerations in the planned removal group, and
      9/79 (11.4%) in the removal after labor group (odds ratio 0.70, 95% confidence
      interval 0.31-1.57). CONCLUSIONS: In summary, planned removal of cerclage before
      labor was not shown to be associated with statistically significant reduction in
      the incidence of cervical lacerations. However, since that our data probably did
      not reach statistical significance because of a type II error, further studies
      are needed.

PMID- 26209806
TI  - Safety modeling of urban arterials in Shanghai, China.
AB  - Traffic safety on urban arterials is influenced by several key variables
      including geometric design features, land use, traffic volume, and travel speeds.
      This paper is an exploratory study of the relationship of these variables to
      safety. It uses a comparatively new method of measuring speeds by extracting GPS
      data from taxis operating on Shanghai's urban network. This GPS derived speed
      data, hereafter called Floating Car Data (FCD) was used to calculate average
      speeds during peak and off-peak hours, and was acquired from samples of 15,000+
      taxis traveling on 176 segments over 18 major arterials in central Shanghai.
      Geometric design features of these arterials and surrounding land use
      characteristics were obtained by field investigation, and crash data was obtained
      from police reports. Bayesian inference using four different models, Poisson
      lognormal (PLN), PLN with Maximum Likelihood priors (PLN-ML), hierarchical PLN
      (HPLN), and HPLN with Maximum Likelihood priors (HPLN-ML), was used to estimate
      crash frequencies. Results showed the HPLN-ML models had the best goodness-of-fit
      and efficiency, and models with ML priors yielded estimates with the lowest
      standard errors. Crash frequencies increased with increases in traffic volume.
      Higher average speeds were associated with higher crash frequencies during peak
      periods, but not during off-peak periods. Several geometric design features
      including average segment length of arterial, number of lanes, presence of non
      motorized lanes, number of access points, and commercial land use, were
      positively related to crash frequencies. 

PMID- 26209808
TI  - Enriched environment decreases microglia and brain macrophages inflammatory
      phenotypes through adiponectin-dependent mechanisms: Relevance to depressive-like
      behavior.
AB  - Regulation of neuroinflammation by glial cells plays a major role in the
      pathophysiology of major depression. While astrocyte involvement has been well
      described, the role of microglia is still elusive. Recently, we have shown that
      Adiponectin (ApN) plays a crucial role in the anxiolytic/antidepressant
      neurogenesis-independent effects of enriched environment (EE) in mice; however
      its mechanisms of action within the brain remain unknown. Here, we show that in a
      murine model of depression induced by chronic corticosterone administration, the
      hippocampus and the hypothalamus display increased levels of inflammatory
      cytokines mRNA, which is reversed by EE housing. By combining flow cytometry,
      cell sorting and q-PCR, we show that microglia from depressive-like mice adopt a
      pro-inflammatory phenotype characterized by higher expression levels of IL-1beta,
      IL-6, TNF-alpha and IkappaB-alpha mRNAs. EE housing blocks pro-inflammatory
      cytokine gene induction and promotes arginase 1 mRNA expression in brain-sorted
      microglia, indicating that EE favors an anti-inflammatory activation state. We
      show that microglia and brain-macrophages from corticosterone-treated mice adopt
      differential expression profiles for CCR2, MHC class II and IL-4recalpha surface
      markers depending on whether the mice are kept in standard environment or EE.
      Interestingly, the effects of EE were abolished when cells are isolated from ApN
      knock-out mouse brains. When injected intra-cerebroventricularly, ApN, whose
      level is specifically increased in cerebrospinal fluid of depressive mice raised
      in EE, rescues microglia phenotype, reduces pro-inflammatory cytokine production
      by microglia and blocks depressive-like behavior in corticosterone-treated mice.
      Our data suggest that EE-induced ApN increase within the brain regulates
      microglia and brain macrophages phenotype and activation state, thus reducing
      neuroinflammation and depressive-like behaviors in mice. 

PMID- 26209807
TI  - Modulation of Sox10, HIF-1alpha, Survivin, and YAP by Minocycline in the
      Treatment of Neurodevelopmental Handicaps following Hypoxic Insult.
AB  - Premature infants are at an increased risk of developing cognitive and motor
      handicaps due to chronic hypoxia. Although the current therapies have reduced the
      incidence of these handicaps, untoward side effects abound. Using a murine model
      of sublethal hypoxia, we demonstrated reduction in several transcription factors
      that modulate expression of genes known to be involved in several neural
      functions. We demonstrate the induction of these genes by minocycline, a
      tetracycline antibiotic with noncanonical functions, in both in vitro and in vivo
      studies. Specifically, there was induction of genes, including Sox10, Hif1a,
      Hif2a, Birc5, Yap1, Epo, Bdnf, Notch1 (cleaved), Pcna, Mag, Mobp, Plp1, synapsin,
      Adgra2, Pecam1, and reduction in activation of caspase 3, all known to affect
      proliferation, apoptosis, synaptic transmission, and nerve transmission.
      Minocycline treatment of mouse pups reared under sublethal hypoxic conditions
      resulted in improvement in open field testing parameters. These studies
      demonstrate beneficial effects of minocycline treatment following hypoxic insult,
      document up-regulation of several genes associated with improved cognitive
      function, and support the possibility of minocycline as a potential therapeutic
      target in the treatment of neurodevelopmental handicaps observed in the very
      premature newborn population. Additionally, these studies may aid in further
      interpretation of the effects of minocycline in the treatment trials and animal
      model studies of fragile X syndrome and multiple sclerosis.

PMID- 26209810
TI  - Dispositional mindfulness is predicted by structural development of the insula
      during late adolescence.
AB  - Adolescence is a critical period of development, in which the increasing social
      and cognitive demands of independence need to be met by enhanced self-regulatory
      abilities. The cultivation of mindfulness has been associated with improved self
      regulation in adult populations, and it is theorized that one neurodevelopmental
      mechanism that supports this capacity is the development of the prefrontal
      cortex. The current study examined the neurodevelopmental mechanisms associated
      with dispositional mindfulness in adolescence. Using a longitudinal within
      persons design, 82 participants underwent structural magnetic resonance imaging
      (MRI) assessments at approximately ages 16 and 19, and also completed self
      reported measurements of mindfulness at age 19. It was hypothesized that
      adolescents who demonstrated greater thinning of frontal cortical regions between
      the age of 16 and 19 would exhibit higher dispositional mindfulness levels at age
      19. Results indicated that, contrary to predictions, adolescents with higher
      levels of mindfulness demonstrated less thinning in the left anterior insula. By
      contrast, higher IQ was associated with greater thinning of the right caudal
      middle frontal and right superior frontal regions. The involvement of insula
      development in mindfulness is consistent with a direct role for this structure in
      managing self-regulation, and in doing so concords with recent models of self
      referential interoceptive awareness. 

PMID- 26209809
TI  - Exogenous testosterone in women enhances and inhibits competitive decision-making
      depending on victory-defeat experience and trait dominance.
AB  - The present experiment tested the causal impact of testosterone on human
      competitive decision-making. According to prevailing theories about
      testosterone's role in social behavior, testosterone should directly boost
      competitive decisions. But recent correlational evidence suggests that
      testosterone's behavioral effects may depend on specific aspects of the context
      and person relevant to social status (win-lose context and trait dominance). We
      tested the causal influence of testosterone on competitive decisions by combining
      hormone administration with measures of trait dominance and a newly developed
      social competition task in which the victory-defeat context was experimentally
      manipulated, in a sample of 54 female participants. Consistent with the
      hypothesis that testosterone has context- and person-dependent effects on
      competitive behavior, testosterone increased competitive decisions after victory
      only among high-dominant individuals but testosterone decreased competitive
      decisions after defeat across all participants. These results suggest that
      testosterone flexibly modulates competitive decision-making depending on prior
      social experience and dominance motivation in the service of enhancing social
      status. 

PMID- 26209811
TI  - Efficient three-component one-pot synthesis of steroidal polysubstituted
      anilines.
AB  - An efficient and practical base-promoted cascade reaction has been developed to
      access steroidal polysubstituted anilines from simple precursors. The protocol
      reported herein achieved the formation of a benzene ring as well as three
      continuous C-C bonds in a single operation. The reaction mechanism was proposed
      on the basis of the key intermediate obtained. Besides, this method could be
      potentially employed for the synthesis of biphenyl compounds. The adjacent amine
      and nitrile groups existed in the final products have the potential for late
      stage functionalization, which would provide efficient access to steroidal
      compound collections with structural diversity and complexity. 

PMID- 26209812
TI  - A bioassay for brassinosteroid activity based on the in vitro fluorimetric
      detection of nitric oxide production.
AB  - Recent studies have shown that low concentrations of brassinolide induce a rapid
      generation of nitric oxide in mesophyll cells of maize leaves, which can be
      easily detected by fluorimetric methods. In this work we describe a series of
      natural and synthetic brassinosteroids that are able to trigger in vitro NO
      production in tomato cells that exhibits dose-response behavior. We propose that
      this effect can be used to develop a new rapid and very sensitive bioassay for
      brassinosteroid activity that offers several advantages when compared to the
      current methodologies. 

PMID- 26209813
TI  - Nitric oxide induces hypoxia ischemic injury in the neonatal brain via the
      disruption of neuronal iron metabolism.
AB  - We have recently shown that increased hydrogen peroxide (H2O2) generation is
      involved in hypoxia-ischemia (HI)-mediated neonatal brain injury. H2O2 can react
      with free iron to form the hydroxyl radical, through Fenton Chemistry. Thus, the
      objective of this study was to determine if there was a role for the hydroxyl
      radical in neonatal HI brain injury and to elucidate the underlying mechanisms.
      Our data demonstrate that HI increases the deposition of free iron and hydroxyl
      radical formation, in both P7 hippocampal slice cultures exposed to oxygen
      glucose deprivation (OGD), and the neonatal rat exposed to HI. Both these
      processes were found to be nitric oxide (NO) dependent. Further analysis
      demonstrated that the NO-dependent increase in iron deposition was mediated
      through increased transferrin receptor expression and a decrease in ferritin
      expression. This was correlated with a reduction in aconitase activity. Both NO
      inhibition and iron scavenging, using deferoxamine administration, reduced
      hydroxyl radical levels and neuronal cell death. In conclusion, our results
      suggest that increased NO generation leads to neuronal cell death during neonatal
      HI, at least in part, by altering iron homeostasis and hydroxyl radical
      generation. 

PMID- 26209814
TI  - Liver fat, statin use, and incident diabetes: The Multi-Ethnic Study of
      Atherosclerosis.
AB  - BACKGROUND AND AIMS: To balance competing cardiovascular benefits and metabolic
      risks of statins, markers of type 2 diabetes (T2D) susceptibility are needed. We
      sought to define a competing risk/benefit of statin therapy on T2D and
      cardiovascular disease (CVD) events using liver attenuation and coronary artery
      calcification (CAC). METHODS AND RESULTS: 3153 individuals from the Multi-Ethnic
      Study of Atherosclerosis (MESA) without CVD, T2D/impaired fasting glucose, or
      baseline statin therapy had CT imaging for CAC and hepatic attenuation (hepatic
      steatosis). Cox models and rates of CVD and T2D were calculated to assess the
      role of liver attenuation in T2D and the relative risks/benefits of statins on
      CVD and T2D. 216 T2D cases were diagnosed at median 9.1 years follow-up. High
      liver fat and statin therapy were associated with diabetes (HR 2.06 [95%CI 1.52
      2.79, P < 0.0001] and 2.01 [95%CI 1.46-2.77, P < 0.0001], respectively), after
      multivariable adjustment. With low liver fat and CAC = 0, the number needed to
      treat (NNT) for statin to prevent one CVD event (NNT 218) was higher than the
      number needed to harm (NNH) with an incident case of T2D (NNH 68). Conversely,
      those with CAC >100 and low liver fat were more likely to benefit from statins
      for CVD reduction (NNT 29) relative to T2D risk (NNH 67). Among those with CAC
      >100 and fatty liver, incremental reduction in CVD with statins (NNT 40) was less
      than incremental risk increase for T2D (NNH 24). CONCLUSIONS: Liver fat is
      associated with incident T2D and stratifies competing metabolic/CVD risks with
      statin therapy. Hepatic fat may inform T2D surveillance and lipid therapeutic
      strategies.

PMID- 26209815
TI  - Inhibiting actin depolymerization enhances osteoblast differentiation and bone
      formation in human stromal stem cells.
AB  - Remodeling of the actin cytoskeleton through actin dynamics is involved in a
      number of biological processes, but its role in human stromal (skeletal) stem
      cells (hMSCs) differentiation is poorly understood. In the present study, we
      demonstrated that stabilizing actin filaments by inhibiting gene expression of
      the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin
      (DSTN) in hMSCs, enhanced cell viability and differentiation into osteoblastic
      cells (OB) in vitro, as well as heterotopic bone formation in vivo. Similarly,
      treating hMSC with Phalloidin, which is known to stabilize polymerized actin
      filaments, increased hMSCs viability and OB differentiation. Conversely,
      Cytocholasin D, an inhibitor of actin polymerization, reduced cell viability and
      inhibited OB differentiation of hMSC. At a molecular level, preventing Cofilin
      phosphorylation through inhibition of LIM domain kinase 1 (LIMK1) decreased cell
      viability and impaired OB differentiation of hMSCs. Moreover, depolymerizing
      actin reduced FAK, p38 and JNK activation during OB differentiation of hMSCs,
      while polymerizing actin enhanced these signaling pathways. Our results
      demonstrate that the actin dynamic reassembly and Cofilin phosphorylation loop is
      involved in the control of hMSC proliferation and osteoblasts differentiation. 

PMID- 26209816
TI  - BMP4 and FGF strongly induce differentiation of mouse ES cells into oral
      ectoderm.
AB  - During embryonic development, oral ectoderm differentiates into the
      adenohypophysis, dental epithelia, salivary glands, and nasal pit. Few reports
      exist concerning the induction of oral ectoderm from embryonic stem (ES) cells.
      Generally, any lot differences in fetal bovine serum (FBS) and serum replacer may
      affect the induction of ES cell-differentiation. Using a previously established
      culture strategy for differentiation, the proportion of cell aggregates
      containing Pitx1+ oral ectoderm varied widely between 9-36% when several
      different lots of FBS or serum replacer were used. We therefore tried to enhance
      the differentiation method. We found that bone morphogenetic protein (BMP) 4 and
      fibroblast growth factor (FGF) treatments improved oral ectoderm induction. Such
      treatment also improved the differentiation of oral ectoderm into the
      adenohypophysis. Furthermore, increased BMP4 treatment induced dental epithelium
      and mesenchyme. Such differentiation suggests that the Pitx1+ layer displays
      similar properties to oral ectoderm, as found in vivo. Differentiation of ES
      cells into oral ectoderm using different lots of FBS and serum replacer increased
      78-90% after treatment with BMP4 and FGF. In summary, we have established a
      robust strategy for the induction of oral ectoderm differentiation from mouse ES
      cells. 

PMID- 26209817
TI  - Novel source of human hematopoietic stem cells from peritoneal dialysis
      effluents.
AB  - Hematopoietic stem cells (HSCs) hold great promise for the treatment of various
      diseases and blood disorders. However, limited availability of these cells has
      hampered their applications in clinical and biological research. Here we have
      identified a new source of autologous human HSCs in peritoneal dialysis (PD)
      effluents from patients with end stage renal diseases (ESRDs). Cells isolated
      from PD effluents contain a Lin-/CD34+/CD38-/CD90+ sub-population and can
      repopulate NOD/SCID/gamma-/- mice in serial transplantation. Differing from cord
      blood HSCs, PD-derived HSCs have high tendencies to repopulate peritoneal cavity
      and spleen with myeloid cells and B lymphocytes. Repopulating HSCs also reside in
      peritoneal cavities in mice. The isolation of HSCs from peritoneal cavities
      provides a novel and promising source of autologous and functional HSCs for stem
      cell research and possible clinical use.

PMID- 26209819
TI  - Mitochondria influence postmortem metabolism and pH in an in vitro model.
AB  - Our objective was to determine the influence of mitochondria on metabolites and
      pH decline using an in vitro model of postmortem muscle metabolism. Mitochondria
      were isolated from porcine longissimus lumborum and added (0, 0.5, or 2.0mg) to
      powdered muscle in reaction media containing either a combination of inhibitors
      for mitochondria complexes (I, IV, and V) or diluent (without inhibitors). In the
      absence of inhibitors, adding mitochondria (0.5 and 2.0mg) reduced ATP loss from
      30 to 120 min, but did not alter glycogen or lactate during this time. In
      reactions with mitochondria, inhibitors decreased ATP levels by 30 min and
      increased glycogen degradation by 60 min. Regardless of mitochondria content,
      inhibitors enhanced lactate accumulation from 15 to 240 min, and decreased pH
      from 15 min to 1440 min. In the in vitro model, mitochondria influence the
      maintenance of ATP, and inhibition of mitochondria enzyme activity contributes to
      accelerated metabolism and pH decline.

PMID- 26209818
TI  - REST-miR-21-SOX2 axis maintains pluripotency in E14Tg2a.4 embryonic stem cells.
AB  - Our previous studies have shown that the regulatory network that maintains
      pluripotency in mouse embryonic stem cells (mESCs) is regulated in a context
      dependent manner and can be modulated, at least in part, by re-calibration of an
      intracellular network of pluripotency factors as well as cues arising from the
      extracellular matrix. The transcriptional repressor REST represses miR-21 and,
      thus, regulates self-renewal in E14Tg2a.4 mESCs cultured in the absence of mouse
      embryonic fibroblast feeder cell effects. However, how miR-21 connects to the
      nuclear regulatory network has not been clear. Here, we show that miR-21, a
      direct target of REST-mediated repression, directly targets Sox2. Exogenously
      added miR-21 to mESCs decreases the expression of Sox2, decreasing mESC self
      renewal, and this effect of miR-21 on mESC self-renewal can be blocked by
      expression of exogenous Sox2. Conversely, destabilization of Sox2 by miR-21 can
      be blocked by anti-miR-21. Thus, the REST-miR-21-Sox2 axis connects REST to the
      core nuclear pluripotency regulators in E14Tg2a.4 mESCs cultured in the absence
      of feeder cells. 

PMID- 26209820
TI  - Asthma and COPD: Interchangeable use of inhalers. A document of Italian Society
      of Allergy, Asthma and Clinical Immmunology (SIAAIC) & Italian Society of
      Respiratory Medicine (SIMeR).
AB  - Prescription cost-containment measures are increasing in many European countries
      and, as more inhaler devices become available, there may be pressure to switch
      patients from reference inhaled medication to cheaper generic inhaled drugs.
      Indeed, in some countries, such a substitution is mandated by current
      regulations, and patients who do not accept the substitution have to pay the
      difference in cost. Generic inhaled drugs are therapeutically equivalent to
      original branded options but may differ in their formulation and inhalation
      device. This new situation raises questions about the potential impact of
      switching from branded to generic inhaled medications in patients with asthma or
      chronic obstructive pulmonary disease (COPD), with or without their consent, in
      countries where this is permitted. Acquisition cost savings from a substitution
      could be offset by costs related to deterioration in asthma control or worsening
      in COPD outcomes if the patient is unable or unwilling to use the inhaler device
      properly. Non-adherence to therapy and incorrect inhaler usage are recognised as
      major factors in uncontrolled asthma and worsening of COPD outcomes. Switching
      patients to a different inhaler device may exacerbate these problems,
      particularly in patients who disagree to switch. Where switching is permitted or
      mandatory, it is crucial that the reason for switching has been properly
      explained to the patient and adequate instruction for operating correctly the
      inhaler have clearly been provided. 

PMID- 26209821
TI  - Assessing and maximizing data quality in macromolecular crystallography.
AB  - The quality of macromolecular crystal structures depends, in part, on the quality
      and quantity of the data used to produce them. Here, we review recent shifts in
      our understanding of how to use data quality indicators to select a high
      resolution cutoff that leads to the best model, and of the potential to greatly
      increase data quality through the merging of multiple measurements from multiple
      passes of single crystals or from multiple crystals. Key factors supporting this
      shift are the introduction of more robust correlation coefficient based
      indicators of the precision of merged data sets as well as the recognition of the
      substantial useful information present in extensive amounts of data once
      considered too weak to be of value. 

PMID- 26209822
TI  - Atypical "vacuum" inside of neoatherosclerosis long term after DES implantation:
      insights from optical coherence tomography.

PMID- 26209823
TI  - Atrial fibrillation is a risk marker for worse in-hospital and long-term outcome
      in patients with peripheral artery disease.
AB  - OBJECTIVES: To investigate the relevance of atrial fibrillation or flutter (AF)
      for outcome of patients who are hospitalized for peripheral artery disease (PAD)
      and/or critical limb ischemia (CLI). METHODS AND RESULTS: We compared baseline
      data, co-morbidities, procedural data as well as in-hospital and long-term
      outcome of 41,882 patients who were hospitalized with PAD or CLI between 2009 and
      2011 according to whether they did or did not have atrial fibrillation/flutter.
      Follow-up was available until December 2012. Of these, 5622 patients (13.4%) had
      AF. AF patients were significantly older (78+/-9 vs. 70+/-11years) and had
      significantly more comorbidities, such as diabetes (40.8 vs. 31.1%), chronic
      kidney disease (40.1 vs. 19.0%), coronary artery disease (38.0 vs. 23.0%) and
      chronic heart failure (26.9 vs. 7.2%, each p<0.001). They had more advanced PAD
      as shown by higher Rutherford classes. In-hospital complications including acute
      renal failure, myocardial infarction, stroke sepsis and death occurred
      significantly more often (each p<0.001). Duration of hospital stay was
      significantly longer and costs were markedly higher in patients with AF (each
      p<0.001). Using multivariate Cox regression analyses regarding long-term
      outcomes, AF was an independent predictor for death (HRR 1.46; 95% CI 1.39-1.52,
      p<0.001), ischemic stroke (HRR 1.63; 95% CI 1.44-1.85) and amputation (HRR 1.14;
      95% CI 1.07-1.21). CONCLUSION: Presence of AF in patients admitted for PAD and
      CLI is associated with worse in-hospital and long-term outcome than in patients
      without AF. This effect was independent of numerous other comorbidities and stage
      of vascular disease.

PMID- 26209824
TI  - Inappropriate shock due to late dislocation of electrode.

PMID- 26209825
TI  - Automated quantification of mitral valve anatomy using anatomical intelligence in
      three-dimensional echocardiography.
AB  - BACKGROUND: Quantitative analysis of mitral valve morphology with three
      dimensional (3D) transesophageal echocardiography (TEE) provides anatomic
      information that can assist clinical decision-making. However, routine use of
      mitral valve quantification has been hindered by tedious workflow and high
      operator-dependence. The purpose of this paper was to evaluate the feasibility,
      accuracy and efficiency of a novel computer-learning algorithm using anatomical
      intelligence in ultrasound (AIUS) to automatically detect and quantitatively
      assess the mitral valve anatomy. METHODS: A novice operator used AIUS to
      quantitatively assess mitral valve anatomy on the 3D TEE images of 55 patients
      (33 with mitral valve prolapse, 11 with functional mitral regurgitation, and 11
      normal valves). The results were compared to that of manual mitral valve
      quantification by an experienced 3D echocardiographer and, in the 24 patients who
      underwent mitral valve repair, the surgical findings. Time consumption and
      reproducibility of AIUS were compared to the manual method. RESULTS: AIUS mitral
      valve quantification was feasible in 52 patients (95%). There were excellent
      agreements between AIUS and expert manual quantification for all mitral valve
      anatomic parameters (r=0.85-0.99, p<0.05). AIUS accurately classified surgically
      defined location of prolapse in 139 of 144 segments analyzed (97%). AIUS improved
      the intra- [intraclass-correlation coefficient (ICC)=0.91-0.99] and inter
      observer (ICC=0.86-0.98) variability of novice users, surpassing the manual
      approach (intra-observer ICC=0.32-0.95; inter-observer ICC=0.45-0.93), yet
      requiring significantly less time (144+/-24s vs. 770+/-89s, p<0.0001).
      CONCLUSION: Anatomic intelligence in 3D TEE image can provide accurate,
      reproducible, and rapid quantification of the mitral valve anatomy.

PMID- 26209826
TI  - Intimal exfoliation following abnormal circular proliferation as a cause for
      acute coronary syndrome in a patient with polycythemia vera.

PMID- 26209827
TI  - Soluble CD146, a new endothelial biomarker of acutely decompensated heart
      failure.
AB  - BACKGROUND: The present study involved both human cohorts and animal experiments
      to explore the performance of soluble CD146 (sCD146), a marker of endothelial
      function, as a diagnostic marker of acutely decompensated heart failure (ADHF),
      to determine the influence of patients' characteristics on that performance and
      to explore the potential application of CD146 in the pathophysiology of ADHF.
      METHODS AND RESULTS: NT-proBNP and sCD146 were measured in three hundred ninety
      one patients admitted to the emergency department for acute dyspnea. ROC curve
      analysis demonstrated that AUCs for ADHF diagnosis in dyspneic patients were 0.86
      (95% CI: 0.82-0.90) for sCD146 and 0.90 (95% CI: 0.86-0.92) for NT-proBNP.
      Subgroup analyses demonstrated that adding sCD146 to NT-proBNP improved the
      diagnostic performance for patients lying in the gray zone of NT-proBNP (p=0.02)
      and could be especially useful for ruling-out ADHF. An experimental model of ADHF
      in rats using thoracic aortic constriction suggests that CD146 is expressed in
      the intima of large arteries and associated with both left ventricular function
      and organ congestion. CONCLUSIONS: sCD146, a marker of endothelial function,
      seems to be as powerful as NT-proBNP is used to detect the cardiac origin of an
      acute dyspnea. The combination of sCD146 and NT-proBNP may have better
      performance than NT-proBNP used alone in particular for patients underlying in
      the "gray" zone and could therefore be an improved option for ruling-out ADHF.
      Both experimental and human data suggest that CD146 is related to systolic left
      ventricular function and to organ congestion.

PMID- 26209828
TI  - Predictors of new onset atrial fibrillation during 10-year follow-up after first
      ever ischemic stroke.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (AF) may be underdiagnosed in ischemic
      stroke patients but may be pivotal for initiation of oral anticoagulation
      therapy. We assessed clinical and ECG predictors of new-onset AF during 10-year
      follow-up (FU) in ischemic stroke patients. METHODS: The study sample comprised
      of 227 first-ever ischemic stroke patients without AF (median age 73,
      interquartile range 25%-75% 63-80years, 92 female) and 1:1 age- and gender
      matched controls without stroke and AF enrolled in the Lund Stroke Register from
      March 2001 to February 2002. New-onset AF during FU was assessed by screening
      through regional ECG database and by record linkage with Swedish National Patient
      Register. The standard 12-lead sinus rhythm ECGs at stroke admission were
      retrieved from electronic database and digitally processed. Clinical baseline
      characteristics were studied using medical records. RESULTS: During FU, AF was
      found in 39 stroke patients and 30 controls, p=0.296. In stroke patients in
      multivariate Cox regression analysis AF was associated with hypertension (HR 3.45
      CI 95% 1.40-3.49, p=0.007) and QRS duration (HR 1.02 CI 95% 1.00-1.03, p=0.049).
      High cardiovascular risk was predictive for AF development: for CHADS2>=4 HR 2.46
      CI 95% 1.45-4.18, p=0.001 and for CHA2DS2-VASc>=5 HR 2.29 CI 95% 1.43-3.68,
      p=0.001. New onset AF was not associated with baseline ischemic stroke: HR 1.46
      95% CI 0.90-2.35, p=0.121. CONCLUSION: High CHADS2 and CHA2DS2-VASc scores, but
      not baseline ischemic stroke, predict new onset AF in FU. QRS duration might be
      considered a potential risk marker for prediction of AF after ischemic stroke.

PMID- 26209829
TI  - Follicular fluid and mural granulosa cells microRNA profiles vary in in vitro
      fertilization patients depending on their age and oocyte maturation stage.
AB  - OBJECTIVE: To determine whether there is any difference in the follicular fluid
      (FF) microRNA (miRNA) profiles from in vitro fertilization (IVF) patients
      according to their age and oocyte maturation stage. DESIGN: Observational
      prospective study. SETTING: IVF clinic/hospital facilities. PATIENTS(S): We
      included 30 women with primary infertility undergoing intracytoplasmic sperm
      injection treatment and excluded patients with polycystic ovarian syndrome,
      endometriosis, severe male factor, and low ovarian reserve. INTERVENTION(S):
      After the collection of FF and granulosa cells from each patient, the samples
      were processed for total RNA extraction. RNA was pooled into different groups
      (three samples per pool) for microarray analysis to evaluate the expression of a
      total of 866 human miRNAs. Individual samples were analyzed to validate the
      pooled microarray results using real-time polymerase chain reaction. MAIN OUTCOME
      MEASURE(S): Evaluation of the expression of a total of 866 human miRNAs in FF and
      granulosa cells. RESULT(S): We identified only one differentially expressed
      miRNA, hsa-miR-424, which is present in higher proportions in FF from patients
      with advanced age. When we compared the FF from metaphase II (MII) versus GV
      (germinal vesicle) oocytes, we found 13 differentially expressed miRNAs (two up-
      and 11 downregulated). When we compared FF from MII versus MI, we found seven
      differentially expressed miRNAs in MII (three up- and four downregulated).
      CONCLUSION(S): We have described the FF miRNA profiles according to IVF patients'
      age and the maturation stage of their oocytes. This descriptive study may aid our
      understanding of the physiology and regulation of oocyte maturation and could
      identify some potential miRNA biomarkers for this process. CLINICAL TRIAL
      REGISTRATION NUMBER: Not applicable.

PMID- 26209830
TI  - Profiling signaling proteins in human spermatozoa: biomarker identification for
      sperm quality evaluation.
AB  - OBJECTIVE: To determine the correlation between semen basic parameters and the
      expression and activity of signaling proteins. DESIGN: In vitro studies with
      human spermatozoa. SETTING: Academic research institute. PATIENT(S): Thirty-seven
      men provided semen samples for routine analysis. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Basic semen parameters tracked included sperm DNA
      fragmentation (SDF), the expression levels of 75 protein kinases, and the
      phosphorylation/cleavage patterns of 18 signaling proteins in human spermatozoa.
      RESULT(S): The results indicated that the phosphorylated levels of several
      proteins (Bad, GSK-3beta, HSP27, JNK/SAPK, mTOR, p38 MAPK, and p53), as well as
      cleavage of PARP (at D214) and Caspase-3 (at D175), were significantly correlated
      with motility parameters. Additionally, the percentage of morphologically normal
      spermatozoa demonstrated a significant positive correlation with the
      phosphorylated levels of p70 S6 kinase and, in turn, head defects and the
      teratozoospermia index (TZI) showed a significant negative correlation with the
      phosphorylated levels of Stat3. There was a significant positive correlation
      between SDF and the teratozoospermia index, as well as the presence of head
      defects. In contrast, SDF negatively correlated with the percentage of
      morphologically normal spermatozoa and the phosphorylation of Akt and p70 S6
      kinase. Subjects with varicocele demonstrated a significant negative correlation
      between head morphological defects and the phosphorylated levels of Akt,
      GSK3beta, p38 MAPK, and Stat1. Additionally, 34 protein kinases were identified
      as expressed in their total protein levels in normozoospermic samples.
      CONCLUSION(S): This study contributed toward establishing a biomarker
      "fingerprint" to assess sperm quality on the basis of molecular parameters.

PMID- 26209831
TI  - Heritability of endometriosis.
AB  - OBJECTIVE: To estimate the relative contribution of genetic influences and
      prevalence on endometriosis. DESIGN: Analysis of self-reported data from a
      nationwide population-based twin registry. SETTING: Not applicable. PATIENT(S): A
      total of 28,370 women, female monozygotic (MZ) or dizygotic (DZ) twins, who
      participated in either of two surveys (1998-2002 or 2005-2006). INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Self-reported endometriosis, validated by medical
      records. RESULT(S): A history of endometriosis was reported by 1,228 female
      twins. The probandwise concordance was 0.21 for MZ and 0.10 for DZ twins. Higher
      within-pair (tetrachoric) correlation was observed among MZ (0.47) compared with
      DZ (0.20) twins. The best-fitting model revealed a contribution of 47% by
      additive genetic factors and the remaining 53% attributed to unique environmental
      effects. CONCLUSION(S): Our findings suggest both genetic and unique (nonshared)
      environmental influences on the complex etiology of endometriosis and support the
      hypothesis that genes have a strong influence on phenotypic manifestations of
      endometriosis.

PMID- 26209832
TI  - Developing a new methodology to characterize in vivo the passive mechanical
      behavior of abdominal wall on an animal model.
AB  - The most common surgical repair of abdominal wall hernia goes through implanting
      a mesh that substitutes the abdominal muscle/fascia while it is healing. To
      reduce the risk of relapse or possible complications, this mesh needs to mimic
      the mechanical behavior of the muscle/fascia, which nowadays is not fully
      determined. The aim of this work is to develop a methodology to characterize in
      vivo the passive mechanical behavior of the abdominal wall. For that, New Zealand
      rabbits were subjected to pneumoperitoneum tests, taking the inner pressure from
      0 mmHg to 12 mmHg, values similar to those used in human laparoscopies. Animals
      treated were divided into two groups: healthy and herniated animals with a
      surgical mesh (polypropylene Surgipro(TM) Covidien) previously implanted. All
      experiments were recorded by a stereo rig composed of two synchronized cameras.
      During the postprocessing of the images, several points over the abdominal
      surface were tracked and their coordinates extracted for different levels of
      internal pressure. Starting from that, a three dimensional model of the abdominal
      wall was reconstructed. Pressure-displacement curves, radii of curvature and
      strain fields were also analysed. During the experiments, animals tissue mostly
      deformed during the first levels of pressure, showing the noticeable hyperelastic
      passive behavior of abdominal muscles. Comparison between healthy and herniated
      specimen displayed a strong stiffening for herniated animals in the zone where
      the high density mesh was situated. Cameras were able to discern this change, so
      this method can be used to measure the possible effect of other meshes.

PMID- 26209833
TI  - N-Alkyl/aryl-4-(3-substituted-3-phenylpropyl)piperazine-1-carbothioamide as dual
      action vaginal microbicides with reverse transcriptase inhibition.
AB  - The growing population and health-care burden (due to STIs and HIV) imposes a
      particular economic crisis over resource-poor countries. Thus a novel approach as
      vaginal microbicides emerges as integrated tool to control both population and
      anti-STIs/HIV. Our continued efforts in this field led to the synthesis of
      fifteen N-alkyl/aryl-4-(3-substituted-3-phenylpropyl) piperazine-1-carbothioamide
      (12-26) derivatives as topical vaginal microbicides which were evaluated for anti
      Trichomonas, spermicidal, antifungal and reverse transcriptase (RT) inhibitory
      activities. All compounds were also tested for preliminary safety through
      cytotoxicity assays against human cervical cell line (HeLa) and the vaginal
      flora, Lactobacillus. Docking studies were performed to gain an insight into the
      binding mode and interactions of the most promising compound 12 [oxo derivative],
      comprising of reverse transcriptase (RT) inhibitory (72.30%), spermicidal (MEC
      0.01%), anti-Trichomonas (MIC 46.72 MUM) and antifungal (MIC 9.34-74.8 MUM)
      activities, along with its hydroxyl (17) and O-alkylated 4-trifluoromethylphenoxy
      (22) derivative, with similar activities. The stability of compound 12 in
      simulated vaginal fluid (SVF) and its preliminary in vivo pharmacokinetics
      performed in female NZ-rabbits signifies its clinical safety in comparison to
      marketed spermicide Nonoxynol-9. 

PMID- 26209834
TI  - Synthesis, pharmacological evaluation and docking studies of pyrrole structure
      based CB2 receptor antagonists.
AB  - During the last years, there has been a continuous interest in the development of
      cannabinoid receptor ligands that may serve as therapeutic agents and/or as
      experimental tools. This prompted us to design and synthesize analogues of the
      CB2 receptor antagonist N-fenchyl-5-(4-chloro-3-methyl-phenyl)-1-(4-methyl
      benzyl)-1H-pyrazole-3-carboxamide (SR144528). The structural modifications
      involved the bioisosteric replacement of the pyrazole ring by a pyrrole ring and
      variations on the amine carbamoyl substituents. Two of these compounds, the
      fenchyl pyrrole analogue 6 and the myrtanyl derivative 10, showed high affinity
      (Ki in the low nM range) and selectivity for the CB2 receptor and both resulted
      to be antagonists/inverse agonists in [(35)S]-GTPgammaS binding analysis and in
      an in vitro CB2 receptor bioassay. Cannabinoid receptor binding data of the
      series allowed identifying steric constraints within the CB2 binding pocket using
      a study of Van der Waals' volume maps. Glide docking studies revealed that all
      docked compounds bind in the same region of the CB2 receptor inactive state
      model. 

PMID- 26209835
TI  - Landscaping the structures of GAVI country vaccine supply chains and testing the
      effects of radical redesign.
AB  - BACKGROUND: Many of the world's vaccine supply chains do not adequately provide
      vaccines, prompting several questions: how are vaccine supply chains currently
      structured, are these structures closely tailored to individual countries, and
      should these supply chains be radically redesigned? METHODS: We segmented the 57
      GAVI-eligible countries' vaccine supply chains based on their
      structure/morphology, analyzed whether these segments correlated with differences
      in country characteristics, and then utilized HERMES to develop a detailed
      simulation model of three sample countries' supply chains and explore the cost
      and impact of various alternative structures. RESULTS: The majority of supply
      chains (34 of 57) consist of four levels, despite serving a wide diversity of
      geographical areas and population sizes. These four-level supply chains loosely
      fall into three clusters [(1) 18 countries relatively more bottom-heavy, i.e.,
      many more storage locations lower in the supply chain, (2) seven with relatively
      more storage locations in both top and lower levels, and (3) nine comparatively
      more top-heavy] which do not correlate closely with any of the country
      characteristics considered. For all three cluster types, our HERMES modeling
      found that simplified systems (a central location shipping directly to
      immunization locations with a limited number of Hubs in between) resulted in
      lower operating costs. CONCLUSION: A standard four-tier design template may have
      been followed for most countries and raises the possibility that simpler and more
      tailored designs may be warranted.

PMID- 26209836
TI  - Demographic characteristics of members of the Vaccine Safety Datalink (VSD): A
      comparison with the United States population.
AB  - BACKGROUND: The Vaccine Safety Datalink (VSD) is a collaboration between CDC and
      nine integrated health care systems that serves as a cornerstone of US post
      licensure vaccine safety monitoring. Given concerns that potential differences
      between the insured VSD population and the US population could limit the
      generalizability of VSD study findings, we performed a comparison of the
      demographic characteristics between the two populations. METHODS: We collected
      data from medical records and administrative files at VSD sites in 2010 to
      compare sex, age, race, ethnicity, income, and educational attainment to the 2010
      US Census population. We also compared data on the 2012 VSD Medicaid population
      to 2012 US Medicaid data. RESULTS: The VSD population included over eight million
      individuals in 2010, which represented 2.6% of the total US population. All major
      demographic groups were represented in the VSD. We found no major differences in
      comparing sex, race, ethnicity, and educational attainment between the VSD and
      the US population. Middle income populations were comparable between the VSD and
      the US. While the percentage of lower income populations was less in the VSD
      compared to the US, the VSD had over two million individuals in this group.
      Additionally, there were over 600,000 Medicaid members in the VSD in 2012, which
      represented 1.1% of the US Medicaid population. CONCLUSIONS: We found that the
      VSD population is representative of the general US population on several key
      demographic and socioeconomic variables. Despite a few specific groups being
      underrepresented in the VSD compared to the US, the absolute number of VSD
      members is large enough to ensure significant representation of these groups in
      vaccine safety studies that use VSD data.

PMID- 26209837
TI  - Surveillance of congenital rubella and rubella infections in pregnancy in EU/EEA
      countries, 2012: Current status and future perspective to monitor elimination.
AB  - INTRODUCTION: Rubella elimination and congenital rubella syndrome (CRS)
      prevention are targets for achievement by 2015 in the WHO-EURO Region. This paper
      describes the existing surveillance systems for CRS and rubella in pregnancy in
      order to critically interpret the findings in relation to the 2012 WHO-EURO
      surveillance guidelines. METHODS: In 2012 we conducted a survey to collect
      information on surveillance of CRS and rubella in pregnancy in 29 EU/EEA
      countries. Questionnaires explored the characteristics of the surveillance
      systems, case definition, epidemiological investigation and follow-up of cases,
      reference laboratories and types of tests performed. RESULTS: Twenty-eight
      countries had surveillance systems for CRS, mostly nationwide, mandatory, passive
      and case-based; 23 collected information on the origin of the infection; 11
      reported asymptomatic infections; 6 required zero-reporting. Case definitions
      varied among countries, although 24 used the EU definition. Laboratories reported
      cases in 18 countries. Twenty countries collected information on pregnancy within
      the rubella surveillance system and 5 had specific surveillance for rubella in
      pregnancy. Two countries did not monitor outcomes of suspected infections in
      pregnancy; infants with CRS were monitored in all the remaining countries;
      asymptomatic infected infants in 15; stillbirths and fetal deaths in 13;
      therapeutic and spontaneous abortions in 8 and 7. Twenty-seven countries had a
      national reference laboratory for CRS and rubella in pregnancy; genotyping was
      performed in 15. DISCUSSION: The current surveillance systems allow adequate CRS
      monitoring in EU. Further efforts are needed to improve their quality, including
      uniform case definitions, collection of information on the origin of infection,
      and promotion of reporting from laboratories. Follow-up of pregnant women with
      suspected infection should be strengthened because it is an entry point for CRS,
      including detection of fetal deaths, stillbirths and abortions. Laboratory
      capacity for confirming congenital rubella infections and infections in pregnancy
      is good in EU, however the use of genotyping should be encouraged.

PMID- 26209838
TI  - Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS).
AB  - The Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug
      Administration (FDA) conduct post-licensure vaccine safety monitoring using the
      Vaccine Adverse Event Reporting System (VAERS), a spontaneous (or passive)
      reporting system. This means that after a vaccine is approved, CDC and FDA
      continue to monitor safety while it is distributed in the marketplace for use by
      collecting and analyzing spontaneous reports of adverse events that occur in
      persons following vaccination. Various methods and statistical techniques are
      used to analyze VAERS data, which CDC and FDA use to guide further safety
      evaluations and inform decisions around vaccine recommendations and regulatory
      action. VAERS data must be interpreted with caution due to the inherent
      limitations of passive surveillance. VAERS is primarily a safety signal detection
      and hypothesis generating system. Generally, VAERS data cannot be used to
      determine if a vaccine caused an adverse event. VAERS data interpreted alone or
      out of context can lead to erroneous conclusions about cause and effect as well
      as the risk of adverse events occurring following vaccination. CDC makes VAERS
      data available to the public and readily accessible online. We describe
      fundamental vaccine safety concepts, provide an overview of VAERS for healthcare
      professionals who provide vaccinations and might want to report or better
      understand a vaccine adverse event, and explain how CDC and FDA analyze VAERS
      data. We also describe strengths and limitations, and address common
      misconceptions about VAERS. Information in this review will be helpful for
      healthcare professionals counseling patients, parents, and others on vaccine
      safety and benefit-risk balance of vaccination. 

PMID- 26209839
TI  - Paresthesia and sensory disturbances associated with 2009 pandemic vaccine
      receipt: Clinical features and risk factors.
AB  - BACKGROUND: Paresthesia was the third-most-common adverse event following
      immunization (AEFI) with 2009 monovalent AS03-adjuvanted A(H1N1)pdm09 vaccine in
      Quebec, Canada and was also frequently reported in Europe. This study assessed
      clinical features and risk factors associated with this unexpected AEFI. METHODS:
      Reports to the passive surveillance system were summarized. A case-control study
      was conducted to assess risk factors and additional investigations were
      undertaken among cases with symptoms persisting >=12 months. RESULTS: There were
      328 reports of paresthesia affecting the vaccinated arm (58%), but also face
      (45%), lower limbs (40%) and back/thorax (23%) with numbness but also muscle
      weakness (61%), motor impairment (61%), generalized myalgia (37%), visual (14%)
      and/or speech effects (15%). Reporting rate was highest in women of reproductive
      age, peaking at 30-39 years-old (28/100,000 doses administered) and exceeding
      that of men of the same age (7/100,000 doses) by 4-fold. Median time to onset was
      2h. Symptoms subsided within one week in 37% but lasted >=6 months in 26%. No
      consistent or objective neurological findings were identified. Risk was increased
      with allergy history, respiratory illness the day of vaccination, depressive
      symptoms and family history of pulmonary disease, but decreased with physical
      activity the day of vaccination, and regular weekly alcohol consumption.
      CONCLUSION: Paresthesia following 2009 pandemic vaccine receipt lasted several
      weeks and included other motor-sensory disturbances in an important subset of
      patients. Although it does not correspond with known neurological disease, and
      causality remains uncertain, further investigation is warranted to understand the
      nature and frequency of paresthesia as a possible AEFI with influenza vaccines.

PMID- 26209840
TI  - Recognition of core-derived epitopes from a novel HBV-targeted immunotherapeutic
      by T-cells from patients infected by different viral genotypes.
AB  - Hepatitis B virus (HBV) infects millions of people worldwide and is a leading
      cause of liver cirrhosis and hepatocellular carcinoma. Current therapies based on
      nucleos(t)ide analogs or pegylated-interferon-alpha lead to control of viral
      replication in most patients but rarely achieve cure. A potential strategy to
      control chronic hepatitis B is to restore or induce functional anti-HBV T-cell
      immune responses using HBV-specific immunotherapeutics. However, viral diversity
      is a challenge to the development of this class of products as HBV genotypes
      display a sequence diversity of up to 8%. We have developed a novel HBV-targeted
      immunotherapeutic, TG1050, based on a non-replicative Adenovirus vector encoding
      a unique and large fusion protein composed of multiple antigenic regions derived
      from a HBV genotype D sequence. Using peripheral blood mononuclear cells from 23
      patients chronically infected by five distinct genotypes (gt A, B, C, D and E)
      and various sets of peptides encompassing conserved versus divergent regions of
      HBV core we have measured ability of TG1050 genotype D core-derived peptides to
      be recognized by T-cells from patients infected by various genotypes. Overall,
      PBMCs from 78% of genotype B or C- and 100% genotype A or E-infected patients
      lead to detection of HBV core-specific T-cells recognizing genotype D antigenic
      domains located both in conserved and variable regions. This proof-of-concept
      study supports the clinical development of TG1050 in large patient populations
      independently of infecting genotypes. 

PMID- 26209841
TI  - Diphtheria, tetanus, poliomyelitis, yellow fever and hepatitis B seroprevalence
      among HIV1-infected migrants. Results from the ANRS VIHVO vaccine sub-study.
AB  - BACKGROUND: Few data are available on the seroprotection status of HIV1-infected
      patients with respect to vaccine-preventable diseases. OBJECTIVE: To describe, in
      a population of HIV1-infected migrants on stable, effective ART therapy, the
      seroprevalence of diphtheria, poliomyelitis, tetanus, yellow fever antibodies and
      serostatus for hepatitis B, and to identify factors associated with
      seroprotection. Vaccine responses against diphtheria, tetanus, poliomyelitis and
      yellow fever were also studied. METHODS: Sub-Saharan African patients
      participating in the ANRS-VIHVO cohort were enrolled prior to travel to their
      countries of origin. Serologic analyses were performed in a central laboratory
      before and after the trip. Univariate and multivariate logistic regression was
      used to identify factors associated with initial seroprotection. RESULTS: 250
      patients (99 men and 151 women) were included in the seroprevalence study. Median
      age was 45 years (IQR 39-52), median CD4 cell count was 440/MUL (IQR 336-571),
      and 237 patients (95%) had undetectable HIV1 viral load. The initial
      seroprevalence rates were 69.0% (95%CI 63.2-74.7) for diphtheria, 70.7% (95%CI
      65.0-76.3) for tetanus, and 85.9% (95%CI 81.6-90.2) for yellow fever. Only 64.4%
      (95%CI 58.5-70.3) of patients had protective antibody titers against all three
      poliomyelitis vaccine strains before travel. No serological markers of hepatitis
      B were found in 18.6% of patients (95%CI 13.7-23.3). Patient declaration of prior
      vaccination was the only factor consistently associated with initial
      seroprotection. CONCLUSIONS: We found a low prevalence of seroprotection against
      diphtheria, poliomyelitis, tetanus and hepatitis B. HIV infected migrants living
      in France and traveling to their native countries need to have their vaccine
      schedule completed.

PMID- 26209843
TI  - Separate Brain Circuits Support Integrative and Semantic Priming in the Human
      Language System.
AB  - Semantic priming is a crucial phenomenon to study the organization of semantic
      memory. A novel type of priming effect, integrative priming, has been identified
      behaviorally, whereby a prime word facilitates recognition of a target word when
      the 2 concepts can be combined to form a unitary representation. We used both
      functional and anatomical imaging approaches to investigate the neural substrates
      supporting such integrative priming, and compare them with those in semantic
      priming. Similar behavioral priming effects for both semantic (Bread-Cake) and
      integrative conditions (Cherry-Cake) were observed when compared with an
      unrelated condition. However, a clearly dissociated brain response was observed
      between these 2 types of priming. The semantic-priming effect was localized to
      the posterior superior temporal and middle temporal gyrus. In contrast, the
      integrative-priming effect localized to the left anterior inferior frontal gyrus
      and left anterior temporal cortices. Furthermore, fiber tractography showed that
      the integrative-priming regions were connected via uncinate fasciculus fiber
      bundle forming an integrative circuit, whereas the semantic-priming regions
      connected to the posterior frontal cortex via separated pathways. The results
      point to dissociable neural pathways underlying the 2 distinct types of priming,
      illuminating the neural circuitry organization of semantic representation and
      integration.

PMID- 26209842
TI  - Proper Level of Cytosolic Disabled-1, Which Is Regulated by Dual Nuclear
      Translocation Pathways, Is Important for Cortical Neuronal Migration.
AB  - Disabled-1 (Dab1) is an essential intracellular protein in the Reelin pathway. It
      has a nuclear localization signal (NLS; hereafter referred to as "NLS1") and 2
      nuclear export signals, and shuttles between the nucleus and the cytoplasm. In
      this study, we found that Dab1 has an additional unidentified NLS, and that the
      Dab1 NLS1 mutant could translocate to the nucleus in an unconventional
      ATP/temperature-dependent and cytoplasmic factor/RanGTP gradient-independent
      manner. Additional mutations in the NLS1 mutant revealed that K(67) and K(69) are
      important for the nuclear transport. Furthermore, an excess of the intracellular
      domain of the Reelin receptors inhibited the nuclear translocation of Dab1. An in
      utero electroporation study showed that a large amount of Dab1 in the cytoplasm
      in migrating neurons inhibited the migration, and that forced transport of Dab1
      into the nucleus attenuated this inhibitory effect. In addition, rescue
      experiments using yotari, an autosomal recessive mutant of dab1, revealed that
      cells expressing Dab1 NLS1 mutant tend to distribute at more superficial
      positions than those expressing wild-type Dab1. Taken together, these findings
      suggest that Dab1 has at least 2 NLSs, and that the regulation of the subcellular
      localization of Dab1 is important for the proper migration of excitatory neurons.

PMID- 26209844
TI  - Early Cerebellar Network Shifting in Spinocerebellar Ataxia Type 6.
AB  - Spinocerebellar ataxia 6 (SCA6), an autosomal dominant degenerative disease, is
      characterized by diplopia, gait ataxia, and incoordination due to severe
      progressive degeneration of Purkinje cells in the vestibulo- and spinocerebellum.
      Ocular motor deficits are common, including difficulty fixating on moving
      objects, nystagmus and disruption of smooth pursuit movements. In presymptomatic
      SCA6, there are alterations in saccades and smooth-pursuit movements. We sought
      to assess functional and structural changes in cerebellar connectivity associated
      with a visual task, hypothesizing that gradual changes would parallel disease
      progression. We acquired functional magnetic resonance imaging and diffusion
      tensor imaging data during a passive smooth-pursuit task in 14 SCA6 patients,
      representing a range of disease duration and severity, and performed a cross
      sectional comparison of cerebellar networks compared with healthy controls. We
      identified a shift in activation from vermis in presymptomatic individuals to
      lateral cerebellum in moderate-to-severe cases. Concomitantly, effective
      connectivity between regions of cerebral cortex and cerebellum was at its highest
      in moderate cases, and disappeared in severe cases. Finally, we noted structural
      differences in the cerebral and cerebellar peduncles. These unique results,
      spanning both functional and structural domains, highlight widespread changes in
      SCA6 and compensatory mechanisms associated with cerebellar physiology that could
      be utilized in developing new therapies.

PMID- 26209845
TI  - Context-Dependent Duration Signals in the Primate Prefrontal Cortex.
AB  - The activity of some prefrontal (PF) cortex neurons distinguishes short from long
      time intervals. Here, we examined whether this property reflected a general
      timing mechanism or one dependent on behavioral context. In one task, monkeys
      discriminated the relative duration of 2 stimuli; in the other, they
      discriminated the relative distance of 2 stimuli from a fixed reference point.
      Both tasks had a pre-cue period (interval 1) and a delay period (interval 2) with
      no discriminant stimulus. Interval 1 elapsed before the presentation of the first
      discriminant stimulus, and interval 2 began after that stimulus. Both intervals
      had durations of either 400 or 800 ms. Most PF neurons distinguished short from
      long durations in one task or interval, but not in the others. When neurons did
      signal something about duration for both intervals, they did so in an
      uncorrelated or weakly correlated manner. These results demonstrate a high degree
      of context dependency in PF time processing. The PF, therefore, does not appear
      to signal durations abstractedly, as would be expected of a general temporal
      encoder, but instead does so in a highly context-dependent manner, both within
      and between tasks.

PMID- 26209846
TI  - Regulation of Cortical Dynamic Range by Background Synaptic Noise and Feedforward
      Inhibition.
AB  - The cortex encodes a broad range of inputs. This breadth of operation requires
      sensitivity to weak inputs yet non-saturating responses to strong inputs. If
      individual pyramidal neurons were to have a narrow dynamic range, as previously
      claimed, then staggered all-or-none recruitment of those neurons would be
      necessary for the population to achieve a broad dynamic range. Contrary to this
      explanation, we show here through dynamic clamp experiments in vitro and computer
      simulations that pyramidal neurons have a broad dynamic range under the noisy
      conditions that exist in the intact brain due to background synaptic input.
      Feedforward inhibition capitalizes on those noise effects to control neuronal
      gain and thereby regulates the population dynamic range. Importantly, noise
      allows neurons to be recruited gradually and occludes the staggered recruitment
      previously attributed to heterogeneous excitation. Feedforward inhibition
      protects spike timing against the disruptive effects of noise, meaning noise can
      enable the gain control required for rate coding without compromising the precise
      spike timing required for temporal coding.

PMID- 26209847
TI  - Default Mode Network Activity Predicts Early Memory Decline in Healthy Young
      Adults Aged 18-31.
AB  - Functional magnetic resonance imaging (fMRI) research conducted in healthy young
      adults is typically done with the assumption that this sample is largely
      homogeneous. However, studies from cognitive psychology suggest that long-term
      memory and attentional control begin to diminish in the third decade of life.
      Here, 100 participants between the ages of 18 and 31 learned Lithuanian
      translations of English words in an individual differences study using fMRI. Long
      term memory ability was operationalized for each participant by deriving a memory
      score from 3 convergent measures. Age of participant predicted memory score in
      this cohort. In addition, degree of deactivation during initial encoding in a set
      of regions occurring largely in the default mode network (DMN) predicted both age
      and memory score. The current study demonstrates that early memory decline may
      partially be accounted for by failure to modulate activity in the DMN.

PMID- 26209848
TI  - Cortical Gray and Adjacent White Matter Demonstrate Synchronous Maturation in
      Very Preterm Infants.
AB  - Spatial and functional gradients of development have been described for the
      maturation of cerebral gray and white matter using histological and radiological
      approaches. We evaluated these patterns in very preterm (VPT) infants using
      diffusion tensor imaging. Data were obtained from 3 groups: 1) 22 VPT infants
      without white matter injury (WMI), of whom all had serial MRI studies during the
      neonatal period, 2) 19 VPT infants with WMI, of whom 3 had serial MRI studies and
      3) 12 healthy, term-born infants. Regions of interest were placed in the cortical
      gray and adjacent white matter in primary motor, primary visual, visual
      association, and prefrontal regions. From the MRI data at term-equivalent
      postmenstrual age, differences in mean diffusivity were found in all areas
      between VPT infants with WMI and the other 2 groups. In contrast, minimal
      differences in fractional anisotropy were found between the 3 groups. These
      findings suggest that cortical maturation is delayed in VPT infants with WMI when
      compared with term control infants and VPT infants without WMI. From the serial
      MRI data from VPT infants, synchronous development between gray and white matter
      was evident in all areas and all groups, with maturation in primary motor and
      sensory regions preceding that of association areas. This finding highlights the
      regionally varying but locally synchronous nature of the development of cortical
      gray matter and its adjacent white matter.

PMID- 26209849
TI  - Timing of Cortico-Muscle Transmission During Active Movement.
AB  - Numerous studies have reported large disparities between short cortico-muscle
      conduction latencies and long recorded delays between cortical firing and evoked
      muscle activity. Using methods such as spike- and stimulus-triggered averaging of
      electromyographic (EMG) activity, previous studies have shown that the time delay
      between corticomotoneuronal (CM) cell firing and onset of facilitation of
      forelimb muscle activity ranges from 6.7 to 9.8 ms, depending on the muscle group
      tested. In contrast, numerous studies have reported delays of 60-122 ms between
      cortical cell firing onset and either EMG or movement onset during motor tasks.
      To further investigate this disparity, we simulated rapid active movement by
      applying frequency-modulated stimulus trains to M1 cortical sites in a rhesus
      macaque performing a movement task. This yielded corresponding EMG modulations,
      the latency of which could be measured relative to the stimulus modulations. The
      overall mean delay from stimulus frequency modulation to EMG modulation was 11.5
      +/- 5.6 ms, matching closely the conduction time through the cortico-muscle
      pathway (12.6 +/- 2.0 ms) derived from poststimulus facilitation peaks computed
      at the same sites. We conclude that, during active movement, the delay between
      modulated M1 cortical output and its impact on muscle activity approaches the
      physical cortico-muscle conduction time.

PMID- 26209850
TI  - Additive Routes to Action Learning: Layering Experience Shapes Engagement of the
      Action Observation Network.
AB  - The way in which we perceive others in action is biased by one's prior experience
      with an observed action. For example, we can have auditory, visual, or motor
      experience with actions we observe others perform. How action experience via 1,
      2, or all 3 of these modalities shapes action perception remains unclear. Here,
      we combine pre- and post-training functional magnetic resonance imaging measures
      with a dance training manipulation to address how building experience (from
      auditory to audiovisual to audiovisual plus motor) with a complex action shapes
      subsequent action perception. Results indicate that layering experience across
      these 3 modalities activates a number of sensorimotor cortical regions associated
      with the action observation network (AON) in such a way that the more modalities
      through which one experiences an action, the greater the response is within these
      AON regions during action perception. Moreover, a correlation between left
      premotor activity and participants' scores for reproducing an action suggests
      that the better an observer can perform an observed action, the stronger the
      neural response is. The findings suggest that the number of modalities through
      which an observer experiences an action impacts AON activity additively, and that
      premotor cortical activity might serve as an index of embodiment during action
      observation. 

PMID- 26209851
TI  - Smoking Through a Topography Device Diminishes Some of the Acute Rewarding
      Effects of Smoking.
AB  - BACKGROUND: Smoking topography (ST) devices are an important methodological tool
      for quantifying puffing behavior (eg, puff volume, puff velocity) as well as
      identifying puffing differences across individuals and situations. Available ST
      devices are designed such that the smoker's mouth and hands have direct contact
      with the device rather than the cigarette itself. Given the importance of the
      sensorimotor aspects of cigarette smoking in smoking reward, it is possible that
      ST devices may interfere with the acute rewarding effects of smoking. Despite the
      methodological importance of this issue, few studies have directly compared
      subjective reactions to smoking through a topography device to naturalistic
      smoking. METHODS: Smokers (N = 58; 38% female) smoked their preferred brand of
      cigarettes one time through a portable topography device and one time
      naturalistically, in counterbalanced order across two laboratory sessions.
      Smoking behavior (eg, number of puffs) and subjective effects (eg, urge
      reduction, affect, smoking satisfaction) were assessed. RESULTS: Negative affect
      reduction was greater in the natural smoking condition relative to the topography
      condition, but differences were not significant on measures of urge, withdrawal,
      or positive affect. Self-reported smoking satisfaction, enjoyment of respiratory
      tract sensations, psychological reward, craving reduction, and other rewarding
      effects of smoking were also significantly greater in the naturalistic smoking
      condition. CONCLUSIONS: The effects of using a ST device on the smoking
      experience should be considered when it is used in research as it may diminish
      some of the rewarding effects of smoking. IMPLICATIONS: When considering the
      inclusion of a smoking topography device in one's research, it is important to
      know if use of that device will alter the smoker's experience. This study
      assessed affective and subjective reactions to smoking through a topography
      device compared to naturalistic smoking. We found that smoking satisfaction,
      psychological reward, enjoyment of respiratory tract sensations and other
      rewarding effects were all diminished when smoking through the topography device.
      The effects of using a smoking topography device on the smoking experience should
      be considered when it is used in future research.

PMID- 26209852
TI  - Smoking in Video Games: A Systematic Review.
AB  - INTRODUCTION: Video games are played by a majority of adolescents, yet little is
      known about whether and how video games are associated with smoking behavior and
      attitudes. This systematic review examines research on the relationship between
      video games and smoking. METHODS: We searched MEDLINE, psycINFO, and Web of
      Science through August 20, 2014. Twenty-four studies met inclusion criteria.
      Studies were synthesized qualitatively in four domains: the prevalence and
      incidence of smoking imagery in video games (n = 6), video game playing and
      smoking behavior (n = 11), video game addiction and tobacco addiction (n = 5) and
      genre-specific game playing and smoking behavior (n = 3). RESULTS: Tobacco
      content was present in a subset of video games. The literature is inconclusive as
      to whether exposure to video games as a single construct is associated with
      smoking behavior. Four of five studies found an association between video game
      addiction and smoking. For genre-specific game playing, studies suggest that the
      type of game played affected association with smoking behavior. CONCLUSIONS:
      Research on how playing video games influences adolescents' perceptions of
      smoking and smoking behaviors is still in its nascence. Further research is
      needed to understand how adolescents respond to viewing and manipulating tobacco
      imagery, and whether engaging in game smoking translates into changes in real
      world attitudes or behavior. Smoking imagery in video games may contribute to
      normalizing adolescent smoking. IMPLICATIONS: A large body of research has shown
      that smoking imagery in a variety of media types contributes to adolescent
      smoking uptake and the normalization of smoking behavior, and almost 90% of
      adolescents play video games, yet there has never been a published systematic
      review of the literature on this important topic. This is the first systematic
      review to examine the research on tobacco and video games.We found that tobacco
      imagery is indeed present in video games, the relationship between video game
      playing and smoking remains unclear, there appears to be a correlation between
      problem gaming and smoking and the genre of games may play a role in adolescent
      smoking behavior.

PMID- 26209853
TI  - Challenges in postdischarge function and recovery: the case of fast-track hip and
      knee arthroplasty.
AB  - This narrative review updates the recent advances in our understanding of the
      multifactorial pathogenesis for reduced postdischarge physical and cognitive
      function after fast-track surgery, using total hip and knee arthroplasty as
      surgical models. Relevant factors discussed include the surgical stress responses
      and potential methods for controlling postsurgical inflammation, pain, and
      cognitive dysfunction. The continuation of moderate to severe pain in up to 30%
      of patients for 2-4 weeks calls for better understanding of the underlying
      mechanisms and development of effective multimodal opioid-sparing analgesic
      regimens. The need for the development of effective physiotherapy programmes on a
      patient-specific basis is discussed, along with the need for optimal assessment
      of postoperative function to guide rehabilitation. Other relevant factors
      discussed include the role of orthostatic intolerance, sleep disturbances, and
      blood management, and specific patient populations at risk for adverse outcomes,
      including psychiatric disorders, to identify and guide future interventions for
      optimizing functional postdischarge outcomes after fast-track surgery. 

PMID- 26209854
TI  - The elusive promise of perioperative hyperoxia.

PMID- 26209855
TI  - Neuraxial block and postoperative epidural analgesia: effects on outcomes in the
      POISE-2 trial?.
AB  - BACKGROUND: We assessed associations between intraoperative neuraxial block and
      postoperative epidural analgesia, and a composite primary outcome of death or non
      fatal myocardial infarction, at 30 days post-randomization in POISE-2 Trial
      subjects. METHODS: 10 010 high-risk noncardiac surgical patients were randomized
      aspirin or placebo and clonidine or placebo. Neuraxial block was defined as
      intraoperative spinal anaesthesia, or thoracic or lumbar epidural anaesthesia.
      Postoperative epidural analgesia was defined as postoperative epidural local
      anaesthetic and/or opioid administration. We used logistic regression with
      weighting using estimated propensity scores. RESULTS: Neuraxial block was not
      associated with the primary outcome [7.5% vs 6.5%; odds ratio (OR), 0.89; 95% CI
      (confidence interval), 0.73-1.08; P=0.24], death (1.0% vs 1.4%; OR, 0.84; 95% CI,
      0.53-1.35; P=0.48), myocardial infarction (6.9% vs 5.5%; OR, 0.91; 95% CI, 0.74
      1.12; P=0.36) or stroke (0.3% vs 0.4%; OR, 1.05; 95% CI, 0.44-2.49; P=0.91).
      Neuraxial block was associated with less clinically important hypotension (39% vs
      46%; OR, 0.90; 95% CI, 0.81-1.00; P=0.04). Postoperative epidural analgesia was
      not associated with the primary outcome (11.8% vs 6.2%; OR, 1.48; 95% CI, 0.89
      2.48; P=0.13), death (1.3% vs 0.8%; OR, 0.84; 95% CI, 0.35-1.99; P=0.68],
      myocardial infarction (11.0% vs 5.7%; OR, 1.53; 95% CI, 0.90-2.61; P=0.11],
      stroke (0.4% vs 0.4%; OR, 0.65; 95% CI, 0.18-2.32; P=0.50] or clinically
      important hypotension (63% vs 36%; OR, 1.40; 95% CI, 0.95-2.09; P=0.09).
      CONCLUSIONS: Neuraxial block and postoperative epidural analgesia were not
      associated with adverse cardiovascular outcomes among POISE-2 subjects.

PMID- 26209856
TI  - Intraoperative hypotension and delirium after on-pump cardiac surgery.
AB  - BACKGROUND: Delirium is a common complication after cardiac surgery and may be as
      a result of inadequate cerebral perfusion. We studied delirium after cardiac
      surgery in relation to intraoperative hypotension (IOH). METHODS: This
      observational single-centre, cohort study was nested in a randomized trial, on a
      single intraoperative dose of dexamethasone vs placebo during cardiac surgery.
      During the first four postoperative days, patients were screened for delirium
      based on the Confusion Assessment Method (CAM) for Intensive Care Unit on the
      intensive care unit, CAM on the ward, and by inspection of medical records. To
      combine depth and duration of IOH, we computed the area under the curve for four
      blood pressure thresholds. Logistic regression analyses were performed to
      investigate the association between IOH and the occurrence of postoperative
      delirium, adjusting for confounding and using a 99% confidence interval to
      correct for multiple testing. RESULTS: Of the 734 included patients, 99 patients
      (13%) developed postoperative delirium. The adjusted Odds Ratio for the Mean
      Arterial Pressure <60 mm Hg threshold was 1.04 (99% confidence interval: 0.99
      1.10) for each 1000 mm Hg(2) min(2) AUC(2) increase. IOH, as defined according to
      the other three definitions, was not associated with postoperative delirium
      either. Deep and prolonged IOH seemed to increase the risk of delirium, but this
      was not statistically significant. CONCLUSIONS: Independent of the applied
      definition, IOH was not associated with the occurrence of delirium after cardiac
      surgery.

PMID- 26209857
TI  - Effects of Varenicline on Neural Correlates of Alcohol Salience in Heavy
      Drinkers.
AB  - BACKGROUND: Preclinical and emerging clinical evidence indicates that
      varenicline, a nicotinic partial agonist approved for smoking cessation,
      attenuates alcohol seeking and consumption. Reductions of alcohol craving have
      been observed under varenicline treatment and suggest effects of the medication
      on alcohol reward processing, but this hypothesis remains untested. METHODS: In
      this double-blind, placebo-controlled randomized experimental medicine study, 29
      heavy drinkers underwent a functional magnetic resonance imaging scan after 2
      weeks of varenicline (2mg/d) or placebo administration. During functional
      magnetic resonance imaging, participants performed the Alcohol-Food Incentive
      Delay task, where they could earn points for snacks or alcohol. At baseline and
      after 3 weeks of medication, participants underwent intravenous alcohol self
      administration sessions in the laboratory. RESULTS: During the functional
      magnetic resonance imaging scan, participants in the varenicline group (N=17)
      reported lower feelings of happiness and excitement on subjective mood scales
      when anticipating alcohol reward compared with the placebo group (N=12). Linear
      mixed effects analysis revealed that anticipation of alcohol reward was
      associated with significant blood oxygen level dependent activation of the
      ventral striatum, amygdala, and posterior insula in the placebo group; this
      activation was attenuated in the varenicline group. The varenicline group showed
      no difference in intravenous alcohol self-administration relative to the placebo
      group for either session. Participants with higher insula activation when
      anticipating alcohol reward showed higher alcohol self-administration behavior
      across groups. CONCLUSIONS: Our findings suggest that varenicline decreases blood
      oxygen level dependent activation in striato-cortico-limbic regions associated
      with motivation and incentive salience of alcohol in heavy drinkers. This
      mechanism may underlie the clinical effectiveness of varenicline in reducing
      alcohol intake and indicates its potential utility as a pharmacotherapy for
      alcohol use disorders.

PMID- 26209858
TI  - Making Sense of Optogenetics.
AB  - This review, one of a series of articles, tries to make sense of optogenetics, a
      recently developed technology that can be used to control the activity of
      genetically-defined neurons with light. Cells are first genetically engineered to
      express a light-sensitive opsin, which is typically an ion channel, pump, or G
      protein-coupled receptor. When engineered cells are then illuminated with light
      of the correct frequency, opsin-bound retinal undergoes a conformational change
      that leads to channel opening or pump activation, cell depolarization or
      hyperpolarization, and neural activation or silencing. Since the advent of
      optogenetics, many different opsin variants have been discovered or engineered,
      and it is now possible to stimulate or inhibit neuronal activity or intracellular
      signaling pathways on fast or slow timescales with a variety of different
      wavelengths of light. Optogenetics has been successfully employed to enhance our
      understanding of the neural circuit dysfunction underlying mood disorders,
      addiction, and Parkinson's disease, and has enabled us to achieve a better
      understanding of the neural circuits mediating normal behavior. It has
      revolutionized the field of neuroscience, and has enabled a new generation of
      experiments that probe the causal roles of specific neural circuit components. 

PMID- 26209859
TI  - The Cognitive Effects of Antidepressants in Major Depressive Disorder: A
      Systematic Review and Meta-Analysis of Randomized Clinical Trials.
AB  - BACKGROUND: Cognitive dysfunction is often present in major depressive disorder
      (MDD). Several clinical trials have noted a pro-cognitive effect of
      antidepressants in MDD. The objective of the current systematic review and meta
      analysis was to assess the pooled efficacy of antidepressants on various domains
      of cognition in MDD. METHODS: Trials published prior to April 15, 2015, were
      identified through searching the Cochrane Central Register of Controlled Trials,
      PubMed, Embase, PsychINFO, Clinicaltrials.gov, and relevant review articles. Data
      from randomized clinical trials assessing the cognitive effects of
      antidepressants were pooled to determine standard mean differences (SMD) using a
      random-effects model. RESULTS: Nine placebo-controlled randomized trials (2 550
      participants) evaluating the cognitive effects of vortioxetine (n = 728),
      duloxetine (n = 714), paroxetine (n = 23), citalopram (n = 84), phenelzine (n =
      28), nortryptiline (n = 32), and sertraline (n = 49) were identified.
      Antidepressants had a positive effect on psychomotor speed (SMD 0.16; 95%
      confidence interval [CI] 0.05-0.27; I(2) = 46%) and delayed recall (SMD 0.24; 95%
      CI 0.15-0.34; I(2) = 0%). The effect on cognitive control and executive function
      did not reach statistical significance. Of note, after removal of vortioxetine
      from the analysis, statistical significance was lost for psychomotor speed. Eight
      head-to-head randomized trials comparing the effects of selective serotonin
      reuptake inhibitors (SSRIs; n = 371), selective serotonin and norepinephrine
      reuptake inhibitors (SNRIs; n = 25), tricyclic antidepressants (TCAs; n = 138),
      and norepinephrine and dopamine reuptake inhibitors (NDRIs; n = 46) were
      identified. No statistically significant difference in cognitive effects was
      found when pooling results from head-to-head trials of SSRIs, SNRIs, TCAs, and
      NDRIs. Significant limitations were the heterogeneity of results, limited number
      of studies, and small sample sizes. CONCLUSIONS: Available evidence suggests that
      antidepressants have a significant positive effect on psychomotor speed and
      delayed recall.

PMID- 26209861
TI  - Confocal Laser Endomicroscopy in Inflammatory Bowel Disease--A Systematic Review.
AB  - BACKGROUND AND AIMS: Confocal laser endomicroscopy is an endoscopic method that
      provides in vivo real-time imaging of the mucosa at a cellular level, elucidating
      mucosal changes that are undetectable by white light endoscopy. This paper
      systematically reviews current indications and perspectives of confocal laser
      endomicroscopy for inflammatory bowel disease. METHODS: Available literature was
      searched systematically for studies applying confocal laser endomicroscopy in
      Crohn's disease or ulcerative colitis. Relevant literature was reviewed and only
      studies reporting original clinical data were included. Next, eligible studies
      were analysed with respect to several parameters, such as technique and clinical
      aim and definitions of outcomes. RESULTS: Confocal laser endomicroscopy has been
      used for a wide range of purposes in inflammatory bowel disease, covering
      assessment of inflammatory severity, prediction of therapeutic response and
      relapse and adenoma surveillance in patients with ulcerative colitis. Methods for
      measurement of the histological changes ranged from subjective grading to
      objective quantification analysed by computer-aided models. The studies derived
      their conclusions from assessment of histological features such as colonic
      crypts, epithelial gaps and epithelial leakiness to fluorescein. CONCLUSIONS:
      Confocal laser endomicroscopy remains an experimental but emerging tool for
      assessment of inflammatory bowel disease. It is the only method that enables in
      vivo functional assessment of intestinal barrier function. There is great
      heterogeneity in the literature and no single approach has been validated and
      reproduced to the level of general acceptance.

PMID- 26209860
TI  - Local and Global Resting State Activity in the Noradrenergic and Dopaminergic
      Pathway Modulated by Reboxetine and Amisulpride in Healthy Subjects.
AB  - BACKGROUND: Various psychiatric populations are currently investigated with
      resting state fMRI, with the aim of individualizing diagnostics and treatment
      options and improving treatment outcomes. Many of these studies are conducted in
      large naturalistic samples, providing rich insights regarding disease-related
      neural alterations, but with the common psychopharmacological medication limiting
      interpretations of the results. We therefore investigated the effects of common
      noradrenergic and anti-dopaminergic medications on local and global resting state
      activity (rs-activity) in healthy volunteers to further the understanding of the
      respective effects independent from disease-related alterations. METHODS: Within
      a randomized, double-blind, placebo-controlled crossover design, we investigated
      19 healthy male subjects by resting state fMRI after the intake of reboxetine (4
      mg/d), amisulpride (200mg/d), and placebo for 7 days each. Treatment-related
      differences in local and global rs-activity were measured by the fractional
      amplitude of low frequency fluctuations (fALFF) and resting state functional
      connectivity (rs-FC). RESULTS: fALFF revealed alterations of local rs-activity
      within regions of the core noradrenergic pathway, including the locus coeruleus
      under reboxetine, correlated with its plasma levels. Moreover, reboxetine led to
      increased rs-FC between regions within this pathway, i.e. the locus coeruleus,
      tectum, thalamus, and amygdala. Amisulpride modulated local rs-activity of
      regions within the dopaminergic pathway, with the altered signal in the putamen
      correlating with amisulpride plasma levels. Correspondingly, amisulpride
      increased rs-FC between regions of the dopaminergic pathway comprising the
      substantia nigra and putamen. CONCLUSION: Our data provide evidence of how
      psychopharmacological agents alter local and global rs-activity within the
      respective neuroanatomical pathways in healthy subjects, which may help with
      interpreting data in psychiatric populations.

PMID- 26209862
TI  - The Millennium Development Goals are Dead; Long Live the Sustainable Development
      Goals.

PMID- 26209863
TI  - Immediate postpartum initiation of etonogestrel-releasing implant: A randomized
      controlled trial on breastfeeding impact.
AB  - BACKGROUND: Breast milk volume has never been evaluated when the etonogestrel
      (ENG) implant was inserted immediately postpartum. Thus, this study evaluated if
      the immediate postpartum insertion of the ENG implant alters breast milk volume.
      STUDY DESIGN: Twenty-four postpartum women and their newborns (NBs) were
      randomized into two groups: Implant group (ENG implant inserted within 48 h after
      delivery) and Control group (absence of contraceptive method). The primary
      outcome was the amount of breast milk intake by the NBs in the first 6 weeks
      after delivery. Five and ten grams of deuterium (D(2)O) were orally administered
      to the postpartum women on the day of randomization (day 0) and on the 29th study
      day, respectively. Saliva samples were collected from the mother-NB pairs prior
      to each D(2)O dose administration and after D(2)O ingestion (periodic
      collection). The amount of breast milk ingested by the NBs was estimated by the
      amount of deuterium (D(2)O) ingested by the NBs through breastfeeding, using mass
      spectrometry in the saliva samples. RESULTS: Twenty-four postpartum women and
      their NB were randomized (12 per group). The median of breast milk intake by NBs
      following the two D(2)O doses were similar between groups {first D(2)O dose
      [Implant: 340 mL/day (240-420 mL/day) vs. CONTROL: 330 mL/day (300-530 mL/day),
      p=.54]; second D(2)O dose [Implant: 845 mL/day (770-980 mL/day) vs. CONTROL: 785
      mL/day (680-980 mL/day), p=.63]}. The exclusive breastfeeding rate and NB weight
      were similar between groups in the first 6 weeks postpartum. CONCLUSION: ENG
      implant insertion immediately postpartum does not alter the volume of breast milk
      intake by NBs. IMPLICATIONS: Considering the benefits of immediate postpartum
      initiation of ENG implant on reducing unintended pregnancy and pregnancy
      recurrence, especially in vulnerable populations, our study adds safety data on
      breastfeeding effect of this practice.

PMID- 26209864
TI  - How do duration, frequency, and intensity of exogenous CORT elevation affect
      immune outcomes of stress?
AB  - Stress is typically characterized as "acute" (lasting from minutes to hours) or
      "chronic" (lasting from days to months). These terms are of limited use as they
      are inconsistently used and only encompass one aspect of the stressor (duration).
      Short and long duration stress are generally thought to produce specific outcomes
      (e.g. acute stress enhances while chronic stress suppresses immune function). We
      propose that aspects of stress other than duration, such as frequency and
      intensity, are important in determining its outcome. We experimentally
      manipulated duration, frequency, and intensity of application of exogenous
      corticosterone, CORT, in Sceloporus undulatus (Eastern fence lizards) and
      measured the immune outcomes. Our findings reveal that immune outcomes of stress
      are not easily predicted from the average amount or duration of CORT elevation,
      but that intensity plays an important role. Although three of our treatments
      received the same average amount of CORT, they produced different effects on
      immune outcomes (hemagglutination). As predicted by the literature, short
      duration exposure to low-dose CORT enhanced hemagglutination; however, short
      duration exposure to high-dose CORT suppressed hemagglutination, suggesting that
      stressor intensity affects immune outcomes of stress. While both are
      traditionally termed "acute" based on duration, these treatments produced
      different immune outcomes. Long-duration ("chronic") exposure to CORT did not
      produce the expected suppression of hemagglutination. Frequency of CORT
      application did not alter immune outcomes at low intensities. These results
      highlight the need to quantify more than just the duration of a stressor if we
      are to understand and manage the ecological consequences of stress. Specifically,
      we should consider stressor frequency and intensity, as well as duration, for a
      more complete characterization and understanding of stress. 

PMID- 26209865
TI  - Cortisol but not testosterone is repeatable and varies with reproductive effort
      in wild red deer stags.
AB  - Although it is known that hormone concentrations vary considerably between
      individuals within a population, how they change across time and how they relate
      to an individual's reproductive effort remains poorly quantified in wild animals.
      Using faecal samples collected from wild red deer stags, we examined sources of
      variation in faecal cortisol and androgen metabolites, and the potential
      relationship that these might have with an index of reproductive effort. We also
      biologically validated an assay for measuring androgen metabolites in red deer
      faeces. We show that variation in hormone concentrations between samples can be
      accounted for by the age of the individual and the season when the sample was
      collected. Faecal cortisol (but not androgen) metabolites also showed significant
      among-individual variation across the 10-year sampling time period, which
      accounted for 20% of the trait's phenotypic variance after correcting for the age
      and season effects. Finally, we show that an index of male reproductive effort
      (cumulative harem size) during the mating season (rut) was positively correlated
      with male cortisol concentrations, both among and within individuals. We suggest
      that the highest ranking males have the largest cumulative harem sizes (i.e.
      invest the greatest reproductive effort), and that this social dominance may have
      associated behaviours such as increased frequency of agonistic interactions which
      are associated with corresponding high levels of faecal cortisol metabolites
      (FCM). 

PMID- 26209866
TI  - Vitamin D Deficiency among Adolescent Females with Polycystic Ovary Syndrome.
AB  - STUDY OBJECTIVE: Studies have suggested that low vitamin D levels may play a role
      in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of our study was
      to compare 25-hydroxyvitamin D [25(OH)D] levels in adolescent females with and
      without PCOS. DESIGN, SETTING, AND PARTICIPANTS: Retrospective chart review at a
      tertiary care medical center for female adolescents aged 12-21 years with serum
      25(OH)D measurements within a 5-year period. Participants were categorized as
      having PCOS or as controls based on National Institutes of Health PCOS diagnostic
      criteria. MAIN OUTCOME MEASURE: Exact logistic regression analysis was done to
      compare normal (>=30 ng/mL) vs low (<30 ng/mL) serum 25(OH)D levels in the PCOS
      and control groups. RESULTS: Two hundred ninety-nine charts were reviewed and 107
      participants were included in the study. Of the included participants, 37 were in
      the PCOS group and 70 were in the control group, with a mean age of 15.2 years.
      In the PCOS group, 97.2% were obese and vitamin D deficiency was noted among
      62.2% females. The mean serum 25(OH)D level was 18.4 and 21.6 ng/mL in PCOS and
      control groups, respectively. The difference in mean 25(OH)D levels between the 2
      groups was not statistically significant (P > .05) when controlled for ethnicity,
      body mass index percentile, and season. CONCLUSION: In our study, there was no
      statistically significant difference in mean 25(OH)D levels between PCOS and
      control groups. The majority of participants in PCOS group were obese. Further
      studies in adolescent females with PCOS and normal body mass index could be
      helpful in delineating the role of vitamin D in the pathogenesis of PCOS.

PMID- 26209867
TI  - Attitudes and Perceptions of the Human Papillomavirus Vaccine in Caribbean and
      African American Adolescent boys and Their Parents.
AB  - STUDY OBJECTIVE: Human papillomavirus (HPV) is the most common sexually
      transmitted infection in the world. The prevalence of HPV in men ranges from 20%
      to 65% and is high at all ages. HPV vaccine has high efficacy in preventing HPV
      infection, cervical cancer, and genital warts. The study objectives were to
      describe attitudes and perceptions toward acceptability of HPV vaccination among
      inner-city Caribbean and African American adolescent boys and their parents and
      to identify and discuss correlates that may be associated with these factors.
      DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional survey, administered in a
      general adolescent medicine clinic. Participants were recruited from a
      convenience sample of adolescent boys aged 13 to 19 years currently under care at
      an adolescent medicine clinic. RESULTS: Responses of 101 adolescent boys and 35
      parents were analyzed. Consistent condom use was associated with less interest in
      HPV vaccination; those reporting consistent condom use had an 88% decreased odds
      of being interested in HPV vaccination compared with those reporting inconsistent
      condom uses. Interest in receiving the HPV vaccine was significantly associated
      with having increased numbers of sexual partners. CONCLUSION: Overall, most
      adolescent males (65%) were interested in receiving the HPV vaccine and a
      majority believed their parents would allow the vaccination (77.2%). Parental
      knowledge that the majority of cervical and rectal cancers are caused by HPV
      increased the odds of parents believing their sons need HPV vaccination; however,
      it is not statistically significant.

PMID- 26209868
TI  - Attitudes to HPV Vaccination among Parents of Children Aged 10 to 13 Years.
AB  - STUDY OBJECTIVE: This study aimed to determine the willingness of parents to
      allow their sons and/or daughters aged 10-13 years to be vaccinated for human
      papillomavirus (HPV). DESIGN, SETTING, AND PARTICIPANTS: This was a descriptive
      study conducted in an elementary school to recruit students' parents into the
      study. The sample consisted of 368 (69.1%) parents of children aged 10-13 years
      who were willing to participate in the study as a couple. INTERVENTIONS:
      Questionnaire-based data were collected from the couples. MAIN OUTCOME MEASURES:
      Prior information regarding HPV and vaccination and the opinions of parents of
      children aged 10-13 about HPV vaccination for their daughter or son. RESULTS:
      Only 26.9% of mothers and 25.0% of fathers claimed to be aware of HPV, and only
      24.5% of mothers and 21.2% of fathers claimed to be aware of its vaccine. If the
      vaccine were available in Turkey, 21.6% of mothers and 22.4% of fathers would be
      willing to vaccinate their sons; although the vaccine for girls is available in
      Turkey, only 14.4% of mothers and 15.5% of fathers were willing to vaccinate
      their daughters. CONCLUSIONS: Few participants reported knowing about the HPV
      vaccine, while far fewer intended to vaccinate their daughters and sons against
      the infection. Both males and females should be informed about HPV and its
      vaccine, and initiatives to increase both awareness and the information of health
      care professionals should be encouraged.

PMID- 26209869
TI  - Endoscopic "rescue" treatment for gastrointestinal perforations, anastomotic
      dehiscence and fistula.
AB  - Luminal perforations and anastomotic leaks of the gastrointestinal tract are life
      threatening events with high morbidity and mortality. Early recognition and
      prompt therapy is essential for a favourable outcome. Surgery has long been
      considered the "gold standard" approach for these conditions; however it is
      associated with high re-intervention morbidity and mortality. The recent
      development of endoscopic techniques and devices to manage perforations, leaks
      and fistulae has made non-surgical treatment an attractive and reasonable
      alternative approach. Although endoscopic therapy is widely accepted, comparative
      data of the different techniques are still lacking. In this review we describe,
      benefits and limitations of the current options in the management of patients
      with perforations and leaks, in order to improve outcomes. 

PMID- 26209870
TI  - Cross stress adaptation: Phenomenon of interactions between homotypic and
      heterotypic stressors.
AB  - Individuals have an inherent capacity to cope with stressors in the form of
      stress adaptation. Apart from stress adaptation there is another well documented
      phenomenon known as cross stress adaptation. In this, there is a reduction in
      stress responsiveness to a novel stressor (in which the adapted organism had
      never encountered previously) in previously exposed organisms with another
      stressor given in either continuous or intermittent. However, regarding the
      existence of cross stress adaptation, there are mixed reports revealing that the
      positive cross stress adaptation exists between altitude and heat stress; swim
      and inescapable shock stress, hypoxia and cold stress, psychosocial stressor and
      exercise. However, there are other reports which reveal the non-existence of
      cross adaptation between forced swim and noise stress and cold and immobilized
      stress. The exact mechanisms responsible for cross stress adaptation are not
      defined and need to be investigated. 

PMID- 26209871
TI  - Temperate forest and open landscapes are distinct alternative states as reflected
      in canopy height and tree cover.

PMID- 26209872
TI  - Systematic Review of the Impact of Transition Interventions for Adolescents With
      Chronic Illness on Transfer From Pediatric to Adult Healthcare.
AB  - Transfer from pediatric to adult care is a critical component of a high-quality
      transition experience for adolescents and young adults (AYA) with chronic
      illness. To examine the current evidence regarding the effect of transition
      interventions on care transfer, we performed a systematic review of studies that
      evaluated the effect of transition interventions on the specific health services
      outcome of transfer. The Medline, CINAHL, and PsycINFO databases were searched
      for studies that evaluated 1) a discrete transition intervention for AYA, 2)
      included a comparison group, and 3) reported on the outcome of transfer from
      pediatric to adult healthcare. References were screened and reviewed separately
      by authors, and relevant study details were abstracted during the review process.
      Five studies from five different countries were included in the final analysis.
      All five studies were conducted in specialty care clinics, with three
      interventions involving a nurse practitioner or systems navigator and two
      interventions involving physicians. Four studies were retrospective observational
      studies, and one was a pilot randomized controlled trial. Three of the five
      studies found that the transition intervention was associated with increased
      rates of transfer while the other two showed no statistically significant
      effects. Overall, evaluation of transfer appears to be hindered by methodological
      challenges. Establishing clearer definitions and metrics of transfer and creating
      the infrastructure needed to monitor the transfer of patients more consistently
      are important goals. 

PMID- 26209873
TI  - Self-Management and Transition Readiness Assessment: Development, Reliability,
      and Factor Structure of the STARx Questionnaire.
AB  - INTRODUCTION: The Self-Management and Transition to Adulthood with Rx=Treatment
      (STARx) Questionnaire was developed to collect information on self-management and
      health care transition (HCT) skills, via self-report, in a broad population of
      adolescents and young adults (AYAs) with chronic conditions. METHODS: Over
      several iterations, the STARx questionnaire was created with AYA, family, and
      health provider input. The development and pilot testing of the STARx
      Questionnaire took place with the assistance of 1219 AYAs with different chronic
      health conditions, in multiple institutions and settings over three phases: item
      development, pilot testing, reliability and factor structuring. RESULTS: The
      three development phases resulted in a final version of the STARx Questionnaire.
      The exploratory factor analysis of the third version of the 18-item STARx
      identified six factors that accounted for about 65% of the variance: Medication
      management, Provider communication, Engagement during appointments, Disease
      knowledge, Adult health responsibilities, and Resource utilization. Reliability
      estimates revealed good internal consistency and temporal stability, with the
      alpha coefficient for the overall scale being .80. The STARx was developmentally
      sensitive, with older patients scoring significantly higher on nearly every
      factor than younger patients. CONCLUSION: The STARx Questionnaire is a reliable,
      self-report tool with adequate internal consistency, temporal stability, and a
      strong, multidimensional factor structure. It provides another assessment
      strategy to measure self-management and transition skills in AYAs with chronic
      conditions.

PMID- 26209874
TI  - Prenatal and postnatal manganese teeth levels and neurodevelopment at 7, 9, and
      10.5 years in the CHAMACOS cohort.
AB  - BACKGROUND: Numerous cross-sectional studies of school-age children have observed
      that exposure to manganese (Mn) adversely affects neurodevelopment. However, few
      prospective studies have looked at the effects of both prenatal and postnatal Mn
      exposure on child neurodevelopment. METHODS: We measured Mn levels in prenatal
      and early postnatal dentine of shed teeth and examined their association with
      behavior, cognition, memory, and motor functioning in 248 children aged 7, 9,
      and/or 10.5 years living near agricultural fields treated with Mn-containing
      fungicides in California. We used generalized linear models and generalized
      additive models to test for linear and nonlinear associations, and generalized
      estimating equation models to assess longitudinal effects. RESULTS: We observed
      that higher prenatal and early postnatal Mn levels in dentine of deciduous teeth
      were adversely associated with behavioral outcomes, namely internalizing,
      externalizing, and hyperactivity problems, in boys and girls at 7 and 10.5 years.
      In contrast, higher Mn levels in prenatal and postnatal dentine were associated
      with better memory abilities at ages 9 and 10.5, and better cognitive and motor
      outcomes at ages 7 and 10.5 years, among boys only. Higher prenatal dentine Mn
      levels were also associated with poorer visuospatial memory outcomes at 9 years
      and worse cognitive scores at 7 and 10.5 years in children with higher prenatal
      lead levels (>=0.8 MUg/dL). All these associations were linear and were
      consistent with findings from longitudinal analyses. CONCLUSIONS: We observed
      that higher prenatal and early postnatal Mn levels measured in dentine of
      deciduous teeth, a novel biomarker that provides reliable information on the
      developmental timing of exposures to Mn, were associated with poorer behavioral
      outcomes in school-age boys and girls and better motor function, memory, and/or
      cognitive abilities in school-age boys. Additional research is needed to
      understand the inconsistencies in the neurodevelopmental findings across studies
      and the degree to which differences may be associated with different Mn exposure
      pathways and biomarkers.

PMID- 26209875
TI  - Muscle force modification strategies are not consistent for gait retraining to
      reduce the knee adduction moment in individuals with knee osteoarthritis.
AB  - While gait retraining paradigms that alter knee loads typically focus on
      modifying kinematics, the underlying muscle force modifications responsible for
      these kinematic changes remain largely unknown. As humans are generally thought
      to select uniform gait muscle patterns such as strategies based on fatigue cost
      functions or energy minimization, we hypothesized that a kinematic gait change
      known to reduce the knee adduction moment (i.e. toe-in gait) would be accompanied
      by a uniform muscle force modification strategy for individuals with symptomatic
      knee osteoarthritis. Ten subjects with self-reported knee pain and radiographic
      evidence of medial compartment knee osteoarthritis performed normal gait and toe
      in gait modification walking trials. Two hundred muscle-actuated dynamic
      simulations (10 steps for normal gait and 10 steps from toe-in gait for each
      subject) were performed to determine muscle forces for each gait. Results showed
      that subjects internally rotated their feet during toe-in gait, which decreased
      the foot progression angle by 7 degrees  (p<0.01) and reduced the first peak knee
      adduction moment by 20% (p<0.01). While significant muscle force modifications
      were evidenced within individuals, there were no consistent muscle force
      modifications across all subjects. It may be that self-selected muscle pattern
      changes are not uniform for gait modification particularly for individuals with
      knee pain. Future studies focused on altering knee loads should not assume
      consistent muscle force modifications for a given kinematic gait change across
      subjects and should consider muscle forces in addition to kinematics in gait
      retraining paradigms. 

PMID- 26209876
TI  - Acceleration capability in elite sprinters and ground impulse: Push more, brake
      less?
AB  - Overground sprint studies have shown the importance of net horizontal ground
      reaction force impulse (IMPH) for acceleration performance, but only investigated
      one or two steps over the acceleration phase, and not in elite sprinters. The
      main aim of this study was to distinguish between propulsive (IMPH+) and braking
      (IMPH-) components of the IMPH and seek whether, for an expected higher IMPH,
      faster elite sprinters produce greater IMPH+, smaller IMPH-, or both. Nine high
      level sprinters (100-m best times range: 9.95-10.60s) performed 7 sprints (2*10
      m, 2*15 m, 20 m, 30 m and 40 m) during which ground reaction force was measured
      by a 6.60 m force platform system. By placing the starting-blocks further from
      the force plates at each trial, and pooling the data, we could assess the
      mechanics of an entire "virtual" 40-m acceleration. IMPH and IMPH+ were
      significantly correlated with 40-m mean speed (r=0.868 and 0.802, respectively;
      P<0.01), whereas vertical impulse and IMPH- were not. Multiple regression
      analyses confirmed the significantly higher importance of IMPH+ for sprint
      acceleration performance. Similar results were obtained when considering these
      mechanical data averaged over the first half of the sprint, but not over the
      second half. In conclusion, faster sprinters were those who produced the highest
      amounts of horizontal net impulse per unit body mass, and those who "pushed more"
      (higher IMPH+), but not necessarily those who also "braked less" (lower IMPH-) in
      the horizontal direction.

PMID- 26209877
TI  - Mass spectrometry based characterization of Hb Beckman variant in a falsely
      elevated HbA(1c) sample.
AB  - Glycated hemoglobin (HbA1c) is a 'gold standard' biomarker for assessing the
      glycemic index of an individual. HbA1c is formed due to nonenzymatic
      glycosylation at N-terminal valine residue of the beta-globin chain. Cation
      exchange based high performance liquid chromatography (CE-HPLC) is mostly used to
      quantify HbA1c in blood sample. A few genetic variants of hemoglobin and post
      translationally modified variants of hemoglobin interfere with CE-HPLC-based
      quantification, resulting in its false positive estimation. Using mass
      spectrometry, we analyzed a blood sample with abnormally high HbA1c (52.1%) in
      the CE-HPLC method. The observed HbA1c did not corroborate the blood glucose
      level of the patient. A mass spectrometry based bottom up proteomics approach,
      intact globin chain mass analysis, and chemical modification of the proteolytic
      peptides identified the presence of Hb Beckman, a genetic variant of hemoglobin,
      in the experimental sample. A similar surface area to charge ratio between HbA1c
      and Hb Beckman might have resulted in the coelution of the variant with HbA1c in
      CE-HPLC. Therefore, in the screening of diabetes mellitus through the estimation
      of HbA1c, it is important to look for genetic variants of hemoglobin in samples
      that show abnormally high glycemic index, and HbA1c must be estimated using an
      alternative method. 

PMID- 26209878
TI  - Adolescents' hypochondriacal fears and beliefs: Relationship with demographic
      features, psychological distress, well-being and health-related behaviors.
AB  - OBJECTIVE: There is little previous literature on hypochondriacal attitudes in
      teens. We examined the relationship between adolescents' hypochondriacal fears
      and beliefs, demographic features, psychological distress and well-being, and
      health-related behaviors. METHODS: Nine hundred and forty-eight students (53.4%
      males), aged 14-19years (mean 15.8+/-1.3years), completed the Illness Attitude
      Scales, the Symptom Questionnaire, and the Psychological Well-Being scales.
      Demographic features and health-related behaviors (smoking, alcohol consumption,
      illicit substance use, and sedentary, eating and sleep habits) were also
      collected. RESULTS: Hypochondriacal concerns were significantly higher among
      females and correlated with increased psychological distress and reduced well
      being. One hundred and forty-nine participants (15.7% of the sample) reached the
      threshold of the "hypochondriacal responses", identified by Kellner as a
      screening method for clinically significant hypochondriacal symptoms. The
      "hypochondriacal responses" were significantly associated with higher levels of
      psychological distress, decreased well-being, and some unhealthy behaviors:
      smoking, use of illicit substances, physical inactivity, and short sleep. Female
      gender, physical inactivity, and higher levels of hostility independently
      predicted the "hypochondriacal responses" pattern. CONCLUSIONS: A substantial
      percentage of adolescents experience significant concerns about health. Excessive
      illness fears are associated with less healthy behaviors. A thorough assessment
      of illness-related concerns may be crucial for the prevention of both the
      development of more structured forms of abnormal illness behavior (e.g., severe
      health anxiety) and the engagement in some unhealthy lifestyles in adolescents.
      However, it may also be that unhealthy behaviors lead to increased preoccupation
      with one's own health through adolescents' implicit knowledge about possible
      consequences of such behaviors.

PMID- 26209879
TI  - QSAR study and conformational analysis of 4-arylthiazolylhydrazones derived from
      1-indanones with anti-Trypanosoma cruzi activity.
AB  - A set of 4-arylthiazolylhydrazones derived from 1-indanones (TZHs) previously
      synthesized and assayed against Trypanosoma cruzi, the causative agent of Chagas
      disease, were explored in terms of conformational analysis. We found that TZHs
      can adopt four minimum energy conformations: cis (A, B and C) and trans. The
      possible bioactive conformation was selected by a 3D-QSAR model. Different
      molecular parameters were calculated to produce QSAR second-generation models.
      These QSAR results are discussed in conjunction with conformational analysis from
      molecular modeling studies. The main factor to determine the activity of the
      compounds was the partial charge at the N(3) atom (qN3). The predictive ability
      of the QSAR equations proposed was experimentally validated. The QSAR models
      developed in this study will be helpful to design novel potent TZHs. 

PMID- 26209880
TI  - Phloridzin derivatives inhibiting pro-inflammatory cytokine expression in human
      cystic fibrosis IB3-1 cells.
AB  - Cystic Fibrosis (CF) is the most diffuse autosomal recessive genetic disease
      affecting Caucasians. A persistent recruitment of neutrophils in the bronchi of
      CF patients contributes to exacerbate the airway tissue damage, suggesting that
      modulation of chemokine expression may be an important target for the patient's
      well being thus the identification of innovative anti-inflammatory drugs is
      considered a longterm goal to prevent progressive tissue deterioration.
      Phloridzin, isolated from Malus domestica by a selective molecular imprinting
      extraction, and its structural analogues, Phloridzin heptapropionate (F1) and
      Phloridzin tetrapropionate (F2), were initially investigated because of their
      ability to reduce IL-6 and IL-8 expression in human CF bronchial epithelial cells
      (IB3-1) stimulated with TNF-alpha. Release of these cytokines by CF cells was
      shown to be controlled by the Transcription Factor (TF) NF-kB. The results of the
      present investigation show that of all the derivatives tested, Phloridzin
      tetrapropionate (F2) is the most interesting and has greatest potential as it
      demonstrates inhibitory effects on the expression and production of different
      cytokines involved in CF inflammation processes, including RANTES, VEGF, GM-CSF,
      IL-12, G-CSF, MIP-1b, IL-17, IL-10 and IP-10, without any correlated anti
      proliferative and pro-apoptotic effects. 

PMID- 26209881
TI  - The development of a fast method for recording Schroeder-phase masking functions.
AB  - Schroeder-phase masking complexes have been used in many psychophysical
      experiments to examine the phase curvature of cochlear filtering at
      characteristic frequencies, and other aspects of cochlear nonlinearity. In a
      normal nonlinear cochlea, changing the "scalar factor" of the Schroeder-phase
      masker from -1 through 0 to +1 results in a marked difference in the measured
      masked thresholds, whereas this difference is reduced in ears with damaged outer
      hair cells. Despite the valuable information it may give, one disadvantage of the
      Schroeder-phase masking procedure is the length of the test - using the
      conventional three-alternative forced-choice technique to measure a masking
      function takes around 45 min for one combination of probe frequency and
      intensity. As an alternative, we have developed a fast method of recording these
      functions which uses a Bekesy tracking procedure. Testing at 500 Hz in normal
      hearing participants, we demonstrate that our fast method: i) shows good
      agreement with the conventional method; ii) shows high test-retest reliability;
      and iii) shortens the testing time to 8 min.

PMID- 26209882
TI  - In vivo overactivation of the Notch signaling pathway in the developing cochlear
      epithelium.
AB  - Notch signaling is thought to play important roles in both prosensory domain
      specification and cell fate determination during inner ear development.
      Inhibition of the Notch signaling pathway in prosensory cells results in
      excessive hair cell formation, while activation of the Notch signaling pathway by
      overexpression of activated Notch1 (Notch1-intercellular domain, NICD) in the
      cochlear epithelium results in ectopic sensory patches where NICD is expressed.
      However, the effect of Notch activation on the prosensory domain is not fully
      understood. To elucidate the precise roles of Notch signaling in cochlear
      prosensory epithelium we examined the effects of Notch overactivation on cochlear
      prosensory cells of transgenic mice with conditional NICD expression. The
      histology of the cochlear epithelium was investigated in these mice. The cochlear
      duct of conditional NICD embryos was wide and short, and the epithelium formed an
      abnormal tubular structure. Hair cell numbers were reduced though some hair cells
      developed where NICD was overexpressed. The decrease in hair cells was not
      accompanied by Hes5-positive and Prox1-positive supporting cell overproduction.
      Ectopic expression of early prosensory markers, such as Jag1 and Hes/Hey genes,
      was observed but no expression of Hes5 was found. Our data shows that NICD
      overexpression disrupts the extension of cochlear epithelium, and reduces the
      total numbers of hair cells and supporting cells in the sensory epithelium. Thus,
      an appropriate level of Notch signaling is needed for the normal extension of the
      cochlear epithelium and for differentiation of both hair cells and supporting
      cells. 

PMID- 26209883
TI  - Gender difference in drug use in hospitalized elderly patients.
AB  - PURPOSE: The aims of this study were to evaluate whether or not there are gender
      differences in drug use at hospital admission and prescription at discharge and
      to evaluate the effect of hospitalization on medication patterns in the elderly.
      METHOD: In-patients aged >65years included in the REPOSI registry during a
      recruitment period of 3years (2008-2010-2012) were analyzed in order to evaluate
      drug use at hospital admission and prescription at discharge according to gender.
      RESULTS: A total of 3473 patients, 52% women and 48% men, were considered.
      Polypharmacy (>5 drugs) is more frequent in men both at hospital admission and
      discharge. At hospital discharge, the number of prescriptions increased in both
      sexes at all age groups. Neuropsychiatric drugs were significantly more
      prescribed in women (p<0.0001). At admission men were more likely to be on
      antiplatelets (41.7% vs 36.7%; p=0.0029), ACE-inhibitors (28.7% vs 24.7%;
      p=0.0072) and statins (22.9% vs 18.3%; p=0.0008). At discharge, antiplatelets
      (43.7% vs 37.3%; p=0.0003) and statins (25,2% vs 19.6%; p<0.0001) continued to be
      prescribed more often in men, while women were given beta-blockers more often
      than men (21.8% vs 18.9%; p=0.0340). Proton pump inhibitors were the most
      prescribed drugs regardless of gender. At discharge, the medication pattern did
      not change according to gender. CONCLUSION: Our study showed a gender difference
      in overall medications pattern in the hospitalized elderly. Hospitalization,
      while increasing the number of prescriptions, did not change drug distribution by
      sex.

PMID- 26209884
TI  - Fathers matter: The role of father parenting in preschoolers' executive function
      development.
AB  - Although previous work has shown that mothers' parenting influences the
      development of child executive function (EF; important self-control skills
      developed during the preschool years), the role of fathers' parenting has not
      been thoroughly investigated. We observed fathers' autonomy support and control
      in dyadic play with their 3-year-old children (N pairs=110) and measured father
      and child EF independently with laboratory tasks. We found that fathers'
      controlling parenting was significantly inversely related to the child EF
      composite, above and beyond family income and child verbal ability. These results
      are consistent with the hypothesis that fathers are important for the development
      of EF in their children and suggest that fathers should be included in both
      research and parenting interventions. 

PMID- 26209885
TI  - Emerging roles for IL-11 signaling in cancer development and progression: Focus
      on breast cancer.
AB  - Interleukin (IL)-11 is a member of the IL-6 family of cytokines that is defined
      by the shared use of the GP130 signal transducing receptor subunit. In addition
      of its long recognized activities as a hemopoietic growth factor, IL-11 has an
      emerging role in epithelial cancer biology. Through the activation of the GP130
      Janus kinase signaling cascade and associated transcription factor STAT3, IL-11
      can confer many of the tumor intrinsic 'hallmark' capabilities to neoplastic
      cells, if they express the ligand-specific IL-11Ralpha receptor subunit.
      Accordingly, IL-11 signaling has recently been identified as a rate-limiting step
      for the growth tumors arising from the mucosa of the gastrointestinal tract.
      However, there is less appreciation for a potential role of IL-11 to support
      breast cancer progression, apart from its well documented capacity to facilitate
      bone metastasis. Here we review evidence that IL-11 expression in breast cancer
      correlates with poor disease outcome and discuss some of the molecular mechanisms
      that are likely to underpin these observations. These include the capacity of IL
      11 to stimulate survival and proliferation of cancer cells alongside angiogenesis
      of the primary tumor and of metastatic progenies at distant organs. We review
      current strategies to interfere with IL-11 signaling and advocate that inhibition
      of IL-11 signaling may represent an emerging therapeutic opportunity for numerous
      cancers. 

PMID- 26209886
TI  - Nicotinic receptor activation negatively modulates pro-inflammatory cytokine
      production in multiple sclerosis patients.
AB  - Acetylcholine (ACh) and its receptors of muscarinic and nicotinic types are
      involved in the modulation of immune and inflammatory responses. In present work
      we have characterized the nicotinic receptors expression in PBMC of RR-MS
      patients and healthy donors (HD) and their ability to modulate pro-inflammatory
      cytokines. Here we report that the IL-1beta e IL-17 levels are significantly
      increased in serum of RR-MS patients in respect to HD and that the PBMC
      stimulation with PHA caused a significant increase in pro-inflammatory cytokine
      levels both in RR-MS and HD subjects, with higher increase of protein release in
      RR-MS patients than in HD. The PBMC treatment with PHA plus nicotine produced a
      significant decrease of IL-1beta e IL-17 both as transcript and as protein,
      confirming that the PBMC of the patients respond to the cholinergic stimulation
      more than PBMC of HD. By real time PCR and western blot analysis we have also
      demonstrated that in particular alpha7 receptor subtype appeared expressed at
      comparable levels both in RR-MS patients and HD. The PHA stimulation results to
      inhibit the alpha7 subunit expression while the nicotine causes a significant
      increase in alpha7 transcripts but only in MS patients. The data obtained
      highlight the role of alpha7 receptor subtype in the modulation of anti
      inflammatory cytokines also in MS. Moreover the ability of nicotine to up
      regulate the expression of alpha7 receptor subtype in RR-MS patients, indicates
      that nicotinic receptor stimulation may contribute to down-modulate the
      inflammation occurred in MS by a positive feedback control of its expression. 

PMID- 26209887
TI  - Cognitive Interviewing to Enhance Comprehension and Accuracy of Responses to a
      Spanish-Language Nutrition Program Evaluation Tool.
AB  - OBJECTIVE: To cognitively test a Spanish translation of a questionnaire
      evaluating parent and child food and activity behaviors and assess accuracy of
      understanding and ease of answering. METHODS: Iterative rounds of cognitive
      interviewing, qualitative analysis, and revision were conducted with 19 low
      income, native Spanish-speaking mothers of children aged 3-11 years, in 5
      communities in New York. Key informant interviews were conducted with 2 Spanish
      speaking nutrition educators experienced with the questionnaire. RESULTS: Based
      on responses, improvements were made to (1) ensure clear and familiar wording,
      (2) clarify time frames for specifying the frequency of behaviors, and (3)
      express constructs not amenable to direct translation or for which meanings
      differed by country of origin. Cognitive interviewing results also informed
      improvements to the English language version. CONCLUSIONS AND IMPLICATIONS: Even
      after translation by native speakers, in-depth cognitive interviewing is needed
      to ensure that questionnaires are understood as intended by low-literacy,
      immigrant populations and to facilitate collection of valid evaluation data.

PMID- 26209888
TI  - Not just "a clever way to detect whether DNA really made RNA": The invention of
      DNA-RNA hybridization and its outcome.
AB  - The invention of DNA-RNA hybridization in 1960 by Ben Hall and Sol Spiegelman had
      a powerful impact on the theory and discourse of molecular biology. Yet, despite
      its importance, the story of this invention has barely been told. Hybridization
      allowed biologists to bridge the theoretical realm and the material world of
      organisms, to correlate a hypothetical concept of biological information transfer
      with a mechanism capable of making an RNA copy of DNA. During the early 1960s,
      Spiegelman and coworkers employed hybridization to investigate the origin of RNAs
      found in cells. They operationally defined messenger RNA and elucidated several
      aspects of genome organization. For Spiegelman, this was the culmination of his
      longstanding interest in the mechanism of enzyme/protein synthesis; for Hall, it
      was the beginning of a successful career in genetics. Other scientists
      immediately recognized the power of the technique and introduced improvements. In
      1965, Gillespie and Spiegelman combined several modifications and described a
      procedure for hybridization that became standard. Since the 1970s, it has become
      an essential tool in biology and in biotechnology, and a core component in
      molecular techniques such as DNA microarrays. Notwithstanding its current
      success, the inventors' names have disappeared from the literature. This
      curiosity is discussed. 

PMID- 26209889
TI  - Reciprocal regulation by hypoxia-inducible factor-2alpha and the NAMPT-NAD(+)
      SIRT axis in articular chondrocytes is involved in osteoarthritis.
AB  - OBJECTIVE: Hypoxia-inducible factor-2alpha (HIF-2alpha) transcriptionally
      upregulates Nampt in articular chondrocytes. NAMPT, which exhibits nicotinamide
      phosphoribosyltransferase activity, in turn causes osteoarthritis (OA) in mice by
      stimulating the expression of matrix-degrading enzymes. Here, we sought to
      elucidate whether HIF-2alpha activates the NAMPT-NAD(+)-SIRT axis in chondrocytes
      and thereby contributes to the pathogenesis of OA. METHODS: Assays of NAD levels,
      SIRT activity, reporter gene activity, mRNA, and protein levels were conducted in
      primary cultured mouse articular chondrocytes. Experimental OA in mice was
      induced by intra-articular (IA) injection of adenovirus expressing HIF-2alpha (Ad
      Epas1) or NAMPT (Ad-Nampt). The functions of SIRT in OA were examined by IA co
      injection of SIRT inhibitors or adenovirus expressing individual SIRT isoforms or
      shRNA targeting specific SIRT isoforms. RESULTS: HIF-2alpha activated the NAMPT
      NAD(+)-SIRT axis in chondrocytes by upregulating NAMPT, which stimulated NAD(+)
      synthesis and thereby activated SIRT family members. The activated NAMPT-SIRT
      pathway, in turn, promoted HIF-2alpha protein stability by negatively regulating
      its hydroxylation and 26S proteasome-mediated degradation, resulting in increased
      HIF-2alpha transcriptional activity. Among SIRT family members (SIRT1-7), SIRT2
      and SIRT4 were positively associated with HIF-2alpha stability and
      transcriptional activity in chondrocytes. This reciprocal regulation was required
      for the expression of catabolic matrix metalloproteinases (MMP3, MMP12, and
      MMP13) and OA cartilage destruction caused by IA injection of Ad-Epas1 Ad-Nampt.
      CONCLUSION: The reciprocal regulation of HIF-2alpha and the NAMPT-NAD(+)-SIRT
      axis in articular chondrocytes is involved in OA cartilage destruction caused by
      HIF-2alpha or NAMPT.

PMID- 26209890
TI  - Neuro-peptide treatment with Cerebrolysin improves the survival of neural stem
      cell grafts in an APP transgenic model of Alzheimer disease.
AB  - Neural stem cells (NSCs) have been considered as potential therapy in Alzheimer's
      disease (AD) but their use is hampered by the poor survival of grafted cells.
      Supply of neurotrophic factors to the grafted cells has been proposed as a way to
      augment survival of the stem cells. In this context, we investigated the utility
      of Cerebrolysin (CBL), a peptidergic mixture with neurotrophic-like properties,
      as an adjunct to stem cell therapy in an APP transgenic (tg) model of AD. We
      grafted murine NSCs into the hippocampus of non-tg and APP tg that were treated
      systemically with CBL and analyzed after 1, 3, 6 and 9months post grafting.
      Compared to vehicle-treated non-tg mice, in the vehicle-treated APP tg mice there
      was considerable reduction in the survival of the grafted NSCs. Whereas, CBL
      treatment enhanced the survival of NSCs in both non-tg and APP tg with the
      majority of the surviving NSCs remaining as neuroblasts. The NSCs of the CBL
      treated mice displayed reduced numbers of caspase-3 and TUNEL positive cells and
      increased brain derived neurotrophic factor (BDNF) and furin immunoreactivity.
      These results suggest that CBL might protect grafted NSCs and as such be a
      potential adjuvant therapy when combined with grafting. 

PMID- 26209891
TI  - Evaluation and Differential Diagnosis of Persistent Marked Eosinophilia.
AB  - Peripheral blood eosinophilia is commonly encountered in clinical practice. The
      causes of peripheral blood eosinophilia are varied, ranging from benign
      eosinophilia to malignancy. A careful history and physical examination along with
      directed clinical evaluation may help determine the cause. When uncontrolled,
      peripheral blood eosinophilia may result in end-organ damage and life-threatening
      complications. This article summarizes the differential diagnosis and evaluation
      of persistent marked eosinophilia. 

PMID- 26209892
TI  - Spectrum of Eosinophilic End-Organ Manifestations.
AB  - Eosinophil-associated disorders can affect practically all tissues and organs in
      the body, either individually or in combination. This article provides an
      overview of end-organ manifestations of eosinophilia and discusses selected organ
      systems, including the upper and lower respiratory, cardiovascular,
      gastrointestinal, nervous, dermatologic, and renal systems. Mechanisms by which
      eosinophilia leads to end-organ damage are also considered. 

PMID- 26209895
TI  - Eosinophilia in Rheumatologic/Vascular Disorders.
AB  - Peripheral and tissue eosinophilia can be a prominent feature of several unique
      rheumatologic and vascular diseases. These diseases span a wide range of clinical
      features, histologic findings, therapeutic approaches, and outcomes. Despite the
      rare nature of these entities--which makes large-scale studies challenging-
      knowledge has continued to grow regarding their epidemiology, pathophysiology,
      and management. This review compares and contrasts 5 rheumatologic and vascular
      conditions in which eosinophilia can be seen: eosinophilic granulomatosis with
      polyangiitis (Churg-Strauss), immunoglobulin G4-related disease, diffuse
      fasciitis with eosinophilia, eosinophilia-myalgia syndrome, and eosinophilic
      myositis.

PMID- 26209894
TI  - Eosinophilia in Hematologic Disorders.
AB  - Eosinophilia in the peripheral blood can be the manifestation various medical
      conditions, including benign or malignant disorders. There are 3 main types of
      eosinophilia-associated myeloid neoplasms (MN-eos): myeloid and lymphoid
      neoplasms, chronic eosinophilic leukemia not otherwise specified, and idiopathic
      hypereosinophilic syndrome (HES). Imatinib mesylate has revolutionized the
      treatment of molecularly defined MN-eos, and novel agents have been successfully
      used to treat HES. The discovery of new, recurrent molecular alterations in
      patients with MN-eos may improve their diagnosis and therapy. This review focuses
      on the hematologist's approach to a patient with eosinophilia and treatment
      options for those with eosinophilic myeloid neoplasms. 

PMID- 26209893
TI  - Eosinophils in Gastrointestinal Disorders: Eosinophilic Gastrointestinal
      Diseases, Celiac Disease, Inflammatory Bowel Diseases, and Parasitic Infections.
AB  - The gastrointestinal (GI) tract provides an intriguing organ for considering the
      eosinophil's role in health and disease. The normal GI tract, except for the
      esophagus, is populated by eosinophils that are present throughout the mucosa,
      raising the possibility that eosinophils participate in innate mechanisms of
      defense. However, data from clinical studies associates increased numbers of
      eosinophils with inflammatory GI diseases, prompting concerns that eosinophils
      may have a deleterious effect on the gut. We present clinical features of 4
      disease processes that have been associated with eosinophilia and suggest areas
      requiring investigation as to their clinical significance and scientific
      relevance. 

PMID- 26209896
TI  - Eosinophilia in Pulmonary Disorders.
AB  - Lung disease associated with marked peripheral blood eosinophilia is unusual and
      nearly always clinically significant. Once recognized, it is generally easy to
      manage, albeit with long-term systemic corticosteroids. A failure to respond to
      oral steroids in the context of good compliance suggests a malignant cause for
      the eosinophilia. An important development is the introduction of antieosinophil
      therapies, particularly those directed against the interleukin 5 pathway, which
      is hoped to provide benefit in the full spectrum of eosinophilic lung disease as
      well as asthma, reducing the burden of side effects and resultant comorbidities. 

PMID- 26209899
TI  - Eosinophilia in Dermatologic Disorders.
AB  - Eosinophil infiltration can be observed in skin disorders, such as
      allergic/immunologic, autoimmune, infectious, and neoplastic diseases. Clinical
      presentations are variable and include eczematous, papular, urticarial, bullous,
      nodular, and fibrotic lesions; pruritus is a common symptom in all. In this
      review, we present representative eosinophilic skin diseases according to their
      clinical pattern, together with histologic findings and diagnostic procedures. We
      also discuss the potential roles of eosinophils in the pathogenesis of
      dermatologic disorder. Current pathogenesis-based diagnostic and therapeutic
      approaches are outlined. 

PMID- 26209898
TI  - Eosinophilia Associated with Disorders of Immune Deficiency or Immune
      Dysregulation.
AB  - Increased serum eosinophil levels have been associated with multiple disorders of
      immune deficiency or immune dysregulation. Although primary immunodeficiency
      diseases are rare, it is important to consider these in the differential
      diagnosis of patients with eosinophilia. In this review, the clinical features,
      laboratory findings, diagnosis, and genetic basis of disease of several disorders
      of immune deficiency or dysregulation are discussed. The article includes
      autosomal dominant hyper IgE syndrome, DOCK8 deficiency, phosphoglucomutase 3
      deficiency, ADA-SCID, Omenn syndrome, Wiskott-Aldrich syndrome, Loeys-Dietz
      syndrome, autoimmune lymphoproliferative syndrome, immunodysregulation,
      polyendocrinopathy, enteropathy, X-linked syndrome, Comel-Netherton syndrome, and
      severe dermatitis, multiple allergies, and metabolic wasting syndrome. 

PMID- 26209900
TI  - Management of Hypereosinophilic Syndromes.
AB  - The symptomatic hypereosinophilic patient must be approached in a stepwise
      manner, with thorough assessment to determine whether the hypereosinophilia
      itself is contributing to damage and disease manifestations (thereby defining a
      hypereosinophilic syndrome), and to identify an eventual cause of
      hypereosinophilia, followed by initiation of treatment directed against the
      underlying condition or deleterious hypereosinophilic state. Situations
      encountered in the clinic are extremely heterogeneous because of the numerous
      potential causes of hypereosinophilia and the variable spectrum of eosinophil
      mediated organ damage. A practical approach to many of these situations is
      presented in this review. 

PMID- 26209897
TI  - Eosinophilia in Infectious Diseases.
AB  - In determining the etiology of eosinophilia, it is necessary to consider the type
      of patient, including previous travel and exposure history, comorbidities, and
      symptoms. In this review, we discuss the approach to the patient with
      eosinophilia from an infectious diseases perspective based on symptom complexes. 

PMID- 26209902
TI  - Eosinophil-Associated Disorders. Preface.

PMID- 26209903
TI  - Characterizing the combined effects of force, repetition and posture on injury
      pathways and micro-structural damage in isolated functional spinal units from sub
      acute-failure magnitudes of cyclic compressive loading.
AB  - BACKGROUND: Previous research suggests that when the magnitude of peak
      compressive force applied during cyclic loading exceeds 30% of a functional
      spinal unit's estimated ultimate compressive tolerance, fatigue failure of the
      cartilaginous endplate or vertebra will occur before intervertebral disc
      herniation. METHODS: Three levels of peak compressive force, three cycle rates
      and two dynamic postural conditions were examined using a full-factorial design.
      Cyclic compressive force was applied using a modified material testing apparatus,
      in accordance with a biofidelic time-varying waveform with synchronous
      flexion/extension rotation for 5000 cycles. Annulus fibrosus tissue from 36
      "survivor" FSUs was excised for histological analysis. RESULTS: 80% of specimens
      survived 5000 cycles of cyclic loading. A marked difference of the magnitude of
      peak compressive force was noted in the Kaplan-Meier survival function of
      experimental conditions that induced fatigue injury. Overall, in the 40% ultimate
      compressive tolerance load condition, the probability of survival was less than
      67%. The micro-structural damage detected in excised samples of annulus fibrosus
      tissue consisted of clefts and fissures within the intra-lamellar matrix, as well
      as delamination within the inter-lamellar matrix. INTERPRETATION: Consistent with
      previous research, our findings support a threshold of peak compressive force of
      30% ultimate compressive tolerance, where cyclic loading above this level will
      likely result in fatigue injury in less than 5000 cycles of in vitro mechanical
      loading. However, findings from our histological analyses demonstrate that
      considerable micro-structural damage occurred in specimens that "survived" the
      cyclic loading exposure.

PMID- 26209901
TI  - Novel Therapies for Eosinophilic Disorders.
AB  - Current therapies for eosinophilic disorders are limited. Most treatment
      approaches remain empirical, are not supported by data from controlled clinical
      trials, involve the off-label use of agents developed for treatment of other
      diseases, and tend to rely heavily on the use of glucocorticoids and other agents
      with significant toxicity. Great progress has been made in the discovery,
      preclinical development, and clinical testing of a variety of biologics and small
      molecules that have the potential to directly or indirectly influence
      eosinophils, eosinophilic inflammation, and the consequences of eosinophil
      activation. 

PMID- 26209904
TI  - Plantarflexor weakness is a determinant of kinetic asymmetry during gait in post
      stroke individuals walking with high levels of effort.
AB  - BACKGROUND: Some studies in post-stroke individuals hypothesized that
      asymmetrical gait might be a strategy to symmetrize the effort in lower limb
      muscles. This study analyzed the asymmetry in the levels of effort, net joint
      moment during gait (walking moment) and maximal potential moment in the
      plantarflexors, hip flexors and extensors during gait. METHODS: Twenty post
      stroke and 10 healthy individuals were assessed when walking at a comfortable
      speed on a treadmill. Their efforts were estimated bilaterally with a
      biomechanical approach (muscular utilization ratio) which is the walking moment
      relative to the muscle's maximal capability (maximal potential moment). Pearson
      correlations were used to assess the relationship between asymmetry in walking
      moment and maximal potential moment. FINDINGS: Healthy individuals presented
      symmetrical values of effort, walking moment and maximal potential moment for all
      muscle groups. Post-stroke individuals had asymmetrical walking moment in
      plantarflexion and hip extension. For the asymmetry in the levels of effort and
      maximal potential moment, they formed two subgroups; the low-effort subgroup
      presented symmetrical effort and their asymmetry in walking moment was not
      related to their asymmetry in maximal potential moment for plantarflexors (R =
      0.44; P > 0.05). The high-effort subgroup presented asymmetrical effort (paretic
      side higher) and their asymmetry in walking moments was significantly associated
      to their asymmetry in maximal potential moment for plantarflexors and hip
      extensors (0.73<=R<=0.82; P<0.05). INTERPRETATION: Asymmetry in muscular strength
      is a determinant of walking moment asymmetry when the level of effort is high.
      These results might guide the type of locomotor training.

PMID- 26209905
TI  - Rituximab in the treatment of patients with systemic sclerosis. Our experience
      and review of the literature.
AB  - BACKGROUND: The treatment of systemic sclerosis (SSc) represents a great clinical
      challenge because of the complex disease pathogenesis including vascular,
      fibrotic, and immune T- and B-lymphocyte-mediated alterations. Therefore, SSc
      should be treated by combined or sequential therapies according to prevalent
      clinico-pathogenetic phenotypes. Some preliminary data suggest that rituximab
      (RTX) may downregulate the B-cell over expression and correlated immunological
      abnormalities. METHODS: Here, we describe a series of 10 SSc patients (4M and 6F,
      mean age 46+/-13.5SD years, mean disease duration 6.3+/-2.7SD years; 5 pts had
      limited and 5 diffuse SSc cutaneous subset) treated with one or more cycles of
      RTX (4 weekly infusions of 375mg/m(2)). The main indications to RTX were
      interstitial lung fibrosis, cutaneous, and/or articular manifestations
      unresponsive to previous therapies; ongoing treatments remained unchanged in all
      cases. The effects of RTX were evaluated after 6months of the first cycle and at
      the end of long-term follow-up period (37+/-21SD months, range 18-72months). An
      updated review of the world literature was also done. RESULTS: RTX significantly
      improved the extent of skin sclerosis in patients with diffuse SSc at 6months
      evaluation (modified Rodnan skin score from 25+/-4.3 to 17.2+/-4.6; p=.022). A
      clinical improvement of other cutaneous manifestations, namely hypermelanosis
      (7/7), pruritus (6/8), and calcinosis (3/6) was observed. Moreover, arthritis
      revealed particularly responsive to RTX showing a clear-cut reduction of swollen
      and tender joints in 7/8 patients; while lung fibrosis detected in 8/10 remained
      stable in 6/8 and worsened in 2/8 at the end of follow-up. Pro-inflammatory
      cytokines, namely IL6, IL15, IL17, and IL23, evaluated in 3 patients with diffuse
      cutaneous SSc, showed a more or less pronounced reduction after the first RTX
      cycle. These observations are in keeping with the majority of previous studies
      including 6 single case reports and 10 SSc series (from 5 to 43 pts), which
      frequently reported the beneficial effects of RTX on some SSc manifestations,
      particularly cutaneous sclerosis, along with the improvement/stabilization of
      lung fibrosis. Possible discrepancies among different clinical studies can be
      related to the etiopathogenetic complexity of SSc and not secondarily to the
      patients' selection and disease duration at the time of the study. CONCLUSION:
      The present study and previous clinical trials suggest a possible therapeutical
      role of RTX in SSc, along with its good safety profile. The specific activity of
      RTX on B-cell-driven autoimmunity might explain its beneficial effects on some
      particular SSc clinical symptoms, namely the improvement of skin and articular
      involvement, and possibly the attenuation of lung fibrosis.

PMID- 26209906
TI  - Emerging role of high mobility group box 1 in ANCA-associated vasculitis.
AB  - High mobility group box 1 (HMGB1) has been suggested to be involved in the
      pathogenesis of many autoimmune diseases. In addition to its nuclear functions,
      extracellular HMGB1 released from activated, injured or dying cells becomes a
      proinflammatory mediator via binding to various receptors on the surface of
      responding cells. HMGB1 interacts with various systems involved in inflammation,
      such as the complement system and the coagulation system. Thus, HMGB1 could
      amplify inflammation and enhance immune responses in pathophysiology of certain
      diseases. In the past years, HMGB1 has been studied in several vasculitides
      including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis,
      Kawasaki disease, Henoch-Schonlein purpura, Takayasu arteritis and giant cell
      arteritis. Several studies showed that circulating HMGB1 levels are higher in
      patients with active disease compared with healthy controls, and levels are
      associated with disease severity. Further studies on pathogenetic mechanisms
      revealed pathogenic roles of HMGB1 in some vasculitides. Here we review clinical
      and experimental studies dealing with the role of HMGB1 in vascular inflammation,
      and its relation to the manifestations and prognosis of specific vasculitides, in
      particular ANCA-associated vasculitis. 

PMID- 26209908
TI  - Perceptions of physiotherapists towards research: a mixed methods study.
AB  - OBJECTIVES: To explore the perceptions of physiotherapists towards the use of and
      participation in research. DESIGN: Concurrent mixed methods research, combining
      in-depth interviews with three questionnaires (demographics, Edmonton Research
      Orientation Survey, visual analogue scales for confidence and motivation to
      participate in research). SETTING: One physiotherapy department in a
      rehabilitation hospital, consisting of seven specialised areas. PARTICIPANTS:
      Twenty-five subjects {four men and 21 women, mean age 38 [standard deviation (SD)
      11] years} who had been registered as a physiotherapist for a mean period of 15
      (SD 10) years participated in this study. They were registered with the New
      Zealand Board of Physiotherapy, held a current practising certificate, and were
      working as a physiotherapist or physiotherapy/allied health manager at the
      hospital. MAIN OUTCOME MEASURE: The primary outcome measure was in-depth
      interviews and the secondary outcome measures were the three questionnaires.
      RESULTS: Physiotherapists were generally positive towards research, but struggled
      with the concept of research, the available literature and the time to commit to
      research. Individual confidence and orientation towards research seemed to
      influence how these barriers were perceived. CONCLUSION: This study showed that
      physiotherapists struggle to implement research in their daily practice and
      become involved in research. Changing physiotherapists' conceptions of research,
      making it more accessible and providing dedicated research time could facilitate
      increased involvement in the physiotherapy profession.

PMID- 26209907
TI  - The role of infectious diseases in the catastrophic antiphospholipid syndrome.
AB  - Catastrophic antiphospholipid syndrome (CAPS), also called "Asherson syndrome",
      is a variant of the antiphospholipid syndrome (APS) that occurs in less than 1%
      of APS cases. The etiology of CAPS is uncertain; however, several triggering
      factors have been recognized. The most common of these are infectious diseases,
      particularly those of the respiratory tract. CAPS pathogenesis is incompletely
      understood, but several theories have been proposed, such as the molecular
      mimicry theory, which describes the production of anti-beta2-glycoprotein I (GP1)
      antibody in response to infection. The process is complex and involves the
      activation of Toll-like receptor 4 (TLR-4), which triggers a cytokine storm,
      followed by endothelial alterations that induce a procoagulant state. 

PMID- 26209909
TI  - Nintendo Wii Fit as an adjunct to physiotherapy following lower limb fractures:
      preliminary feasibility, safety and sample size considerations.
AB  - OBJECTIVE: The Nintendo Wii Fit integrates virtual gaming with body movement, and
      may be suitable as an adjunct to conventional physiotherapy following lower limb
      fractures. This study examined the feasibility and safety of using the Wii Fit as
      an adjunct to outpatient physiotherapy following lower limb fractures, and
      reports sample size considerations for an appropriately powered randomised trial.
      METHODOLOGY: Ambulatory patients receiving physiotherapy following a lower limb
      fracture participated in this study (n=18). All participants received usual care
      (individual physiotherapy). The first nine participants also used the Wii Fit
      under the supervision of their treating clinician as an adjunct to usual care.
      Adverse events, fracture malunion or exacerbation of symptoms were recorded.
      Pain, balance and patient-reported function were assessed at baseline and
      discharge from physiotherapy. RESULTS: No adverse events were attributed to
      either the usual care physiotherapy or Wii Fit intervention for any patient.
      Overall, 15 (83%) participants completed both assessments and interventions as
      scheduled. For 80% power in a clinical trial, the number of complete datasets
      required in each group to detect a small, medium or large effect of the Wii Fit
      at a post-intervention assessment was calculated at 175, 63 and 25, respectively.
      CONCLUSIONS: The Nintendo Wii Fit was safe and feasible as an adjunct to
      ambulatory physiotherapy in this sample. When considering a likely small effect
      size and the 17% dropout rate observed in this study, 211 participants would be
      required in each clinical trial group. A larger effect size or multiple repeated
      measures design would require fewer participants.

PMID- 26209910
TI  - Questioning short-term memory and its measurement: Why digit span measures long
      term associative learning.
AB  - Traditional accounts of verbal short-term memory explain differences in
      performance for different types of verbal material by reference to inherent
      characteristics of the verbal items making up memory sequences. The role of
      previous experience with sequences of different types is ostensibly controlled
      for either by deliberate exclusion or by presenting multiple trials constructed
      from different random permutations. We cast doubt on this general approach in a
      detailed analysis of the basis for the robust finding that short-term memory for
      digit sequences is superior to that for other sequences of verbal material.
      Specifically, we show across four experiments that this advantage is not due to
      inherent characteristics of digits as verbal items, nor are individual digits
      within sequences better remembered than other types of individual verbal items.
      Rather, the advantage for digit sequences stems from the increased frequency,
      compared to other verbal material, with which digits appear in random sequences
      in natural language, and furthermore, relatively frequent digit sequences support
      better short-term serial recall than less frequent ones. We also provide corpus
      based computational support for the argument that performance in a short-term
      memory setting is a function of basic associative learning processes operating on
      the linguistic experience of the rememberer. The experimental and computational
      results raise questions not only about the role played by measurement of digit
      span in cognition generally, but also about the way in which long-term memory
      processes impact on short-term memory functioning. 

PMID- 26209911
TI  - Head-to-Head Comparison of Global Longitudinal Strain Measurements among Nine
      Different Vendors: The EACVI/ASE Inter-Vendor Comparison Study.
AB  - BACKGROUND: This study was planned by the EACVI/ASE/Industry Task Force to
      Standardize Deformation Imaging to (1) test the variability of speckle-tracking
      global longitudinal strain (GLS) measurements among different vendors and (2)
      compare GLS measurement variability with conventional echocardiographic
      parameters. METHODS: Sixty-two volunteers were studied using ultrasound systems
      from seven manufacturers. Each volunteer was examined by the same sonographer on
      all machines. Inter- and intraobserver variability was determined in a true test
      retest setting. Conventional echocardiographic parameters were acquired for
      comparison. Using the software packages of the respective manufacturer and of two
      software-only vendors, endocardial GLS was measured because it was the only GLS
      parameter that could be provided by all manufactures. We compared GLSAV (the
      average from the three apical views) and GLS4CH (measured in the four-chamber
      view) measurements among vendors and with the conventional echocardiographic
      parameters. RESULTS: Absolute values of GLSAV ranged from 18.0% to 21.5%, while
      GLS4CH ranged from 17.9% to 21.4%. The absolute difference between vendors for
      GLSAV was up to 3.7% strain units (P < .001). The interobserver relative mean
      errors were 5.4% to 8.6% for GLSAV and 6.2% to 11.0% for GLS4CH, while the
      intraobserver relative mean errors were 4.9% to 7.3% and 7.2% to 11.3%,
      respectively. These errors were lower than for left ventricular ejection fraction
      and most other conventional echocardiographic parameters. CONCLUSION:
      Reproducibility of GLS measurements was good and in many cases superior to
      conventional echocardiographic measurements. The small but statistically
      significant variation among vendors should be considered in performing serial
      studies and reflects a reference point for ongoing standardization efforts.

PMID- 26209912
TI  - Pitfalls in the Echocardiographic Evaluation of Mitral Annular Size, Shape, and
      Dynamics in Patients with Mitral Annular Calcification.

PMID- 26209913
TI  - Rotator cuff tears in young patients: a different disease than rotator cuff tears
      in elderly patients.
AB  - BACKGROUND: The purpose of this study was to conduct a systematic review of the
      literature to evaluate the characteristics of injury and treatment outcomes of
      rotator cuff tears in young patients. METHODS: A systematic electronic search was
      performed for clinical studies evaluating rotator cuff tears in patients younger
      than 40 years with special emphasis on reporting of injury characteristics and
      treatment outcomes with a minimum 1-year follow-up. RESULTS: Twelve studies
      (involving 336 patients) met inclusion criteria. The mean age of the patients was
      28 years (range, 16-40 years), with a mean follow-up of 39 months. There were 2
      distinct subgroups. The majority of studies (7 of 10) showed that patients
      typically had a full-thickness tear with an acute traumatic etiology. However,
      within the subgroup of elite throwers, 5 of 6 studies demonstrated a majority of
      tears that were partial thickness stemming from chronic overuse. Rotator cuff
      repair improved pain and strength in almost all studies reporting on these
      parameters. Eighty-seven percent of patients reported they were satisfied.
      However, all studies examining elite throwers showed significant difficulty in
      returning to play (25%-97%). CONCLUSIONS: In young patients with rotator cuff
      tears, there are 2 primary groups. (1) A majority group with rotator cuff tears
      of traumatic origin responded well to both arthroscopic and open rotator cuff
      repair in terms of pain relief and self-reported outcomes postoperatively. These
      patients reported high levels of satisfaction and return to preinjury level of
      play. (2) A unique subpopulation composed of elite throwers had improved outcomes
      but suboptimal return to play.

PMID- 26209914
TI  - Has recommended preventive service use increased after elimination of cost
      sharing as part of the Affordable Care Act in the United States?
AB  - BACKGROUND: An early provision of the Affordable Care Act (ACA) eliminated cost
      sharing for a range of recommended preventive services. This provision took
      effect in September 2010, but little is known about its effect on preventive
      service use. METHODS: We evaluated changes in the use of recommended preventive
      services from 2009 (before the implementation of ACA cost-sharing provision) to
      2011/2012 (after the implementation) in the Medical Expenditure Panel Survey, a
      nationally representative household interview survey in the US. Specifically, we
      examined: blood pressure check, cholesterol check, flu vaccination, and cervical,
      breast, and colorectal cancer screening, controlling for demographic
      characteristics and stratifying by insurance type. RESULTS: There were 64,280
      (21,310 before and 42,970 after the implementation of ACA cost-sharing provision)
      adults included in the analyses. Receipt of recent blood pressure check,
      cholesterol check and flu vaccination increased significantly from 2009 to
      2011/2012, primarily in the privately insured population aged 18-64years, with
      adjusted prevalence ratios (95% confidence intervals) 1.03 (1.01-1.05) for blood
      pressure check, 1.13 (1.09-1.18) for cholesterol check and 1.04 (1.00-1.08) for
      flu vaccination (all p-values<0.05). However, few changes were observed for
      cancer screening. We observed little change in the uninsured population.
      CONCLUSIONS: These early observations suggest positive benefits from the ACA
      policy of eliminating cost-sharing for some preventive services. Future research
      is warranted to monitor and evaluate longer term effects of the ACA on access to
      care and health outcomes.

PMID- 26209915
TI  - The stromal cell-surface protease fibroblast activation protein-alpha localizes
      to lipid rafts and is recruited to invadopodia.
AB  - Fibroblast activation protein alpha (FAPalpha) is a cell surface protease
      expressed by cancer-associated fibroblasts in the microenvironment of most solid
      tumors. As there is increasing evidence for proteases having non-catalytic
      functions, we determined the FAPalpha interactome in cancer-associated
      fibroblasts using the quantitative immunoprecipitation combined with knockdown
      (QUICK) method. Complex formation with adenosin deaminase, erlin-2, stomatin,
      prohibitin, Thy-1 membrane glycoprotein, and caveolin-1 was further validated by
      immunoblotting. Co-immunoprecipitation (co-IP) of the known stoichiometric
      FAPalpha binding partner dipeptidyl-peptidase IV (DPPIV) corroborated the
      proteomic strategy. Reverse co-IPs validated the FAPalpha interaction with
      caveolin-1, erlin-2, and stomatin while co-IP upon RNA-interference mediated
      knock-down of DPPIV excluded adenosin deaminase as a direct FAPalpha interaction
      partner. Many newly identified FAPalpha interaction partners localize to lipid
      rafts, including caveolin-1, a widely-used marker for lipid raft localization. We
      hypothesized that this indicates a recruitment of FAPalpha to lipid raft
      structures. In density gradient centrifugation, FAPalpha co-fractionates with
      caveolin-1. Immunofluorescence optical sectioning microscopy of FAPalpha and
      lipid raft markers further corroborates recruitment of FAPalpha to lipid rafts
      and invadopodia. FAPalpha is therefore an integral component of stromal lipid
      rafts in solid tumors. In essence, we provide one of the first interactome
      analyses of a cell surface protease and translate these results into novel
      biological aspects of a marker protein for cancer-associated fibroblasts. 

PMID- 26209916
TI  - Plasma membrane and cytoskeleton dynamics during single-cell wound healing.
AB  - Wounding leads not only to plasma membrane disruption, but also to compromised
      cytoskeleton structures. This results not only in unwarranted exchanges between
      the cytosol and extracellular milieu, but also in loss of tensegrity, which may
      further endanger the cell. Tensegrity can be described as the interplay between
      the tensile forces generated by the apparent membrane tension, actomyosin
      contraction, and the cytoskeletal structures resisting those changes (e.g.,
      microtubules). It is responsible for the structural integrity of the cell and for
      its ability to sense mechanical signals. Recent reviews dealing with single-cell
      healing mostly focused on the molecular machineries controlling the traffic and
      fusion of specific vesicles, or their role in different pathologies. In this
      review, we aim to take a broader view of the different modes of single cell
      repair, while focussing on the different ways the changes in plasmalemma surface
      area and composition, plasmalemma tension, and cytoskeletal dynamics may
      influence and affect single-cell repair. 

PMID- 26209917
TI  - Onyx embolization of a ruptured aneurysm in a patient with moyamoya disease.
AB  - We report a woman who presented with an intraparenchymal hemorrhage. Her cerebral
      angiogram showed a middle cerebral artery (MCA) M1 occlusion with multiple
      collaterals supplying the distal MCA territory, compatible with moyamoya disease.
      Also, an associated 8 mm dysplastic distal aneurysm fed by a left-sided P2
      perforator was seen, collateral from the posterior cerebral artery. The aneurysm
      was successfully occluded with Onyx (ev3 Endovascular, Plymouth, MN, USA)
      embolization. The woman had an uneventful postoperative course. Aneurysm
      formation in patients with moyamoya disease represents a major hemorrhagic risk.
      Several treatment strategies exist including endovascular and surgical
      approaches. Patients with moyamoya disease who present with aneurysmal
      intracerebral hemorrhage should be treated to prevent rebleeding. Onyx
      embolization can be an effective treatment of aneurysms that are associated with
      moyamoya disease and would otherwise be difficult to treat surgically.

PMID- 26209918
TI  - Cervical CT scan-guided epidural blood patches for spontaneous intracranial
      hypotension.
AB  - We describe two patients with spontaneous intracranial hypotension (SIH),
      presenting with postural headache due to C1-C2 cerebrospinal fluid (CSF) leak.
      Both patients were refractory to lumbar epidural blood patching (EBP), and
      subsequently underwent successful CT scan-guided cervical EBP. SIH affects
      approximately 1 in 50,000 patients, with females more frequently affected. Its
      associated features are variable, and as such, misdiagnosis is common. Therefore,
      imaging plays an important role in the diagnostic workup of SIH and can include
      MRI of the brain and spine, CT myelogram, and radionuclide cisternography. In
      patients with an established diagnosis and confirmed CSF leak, symptoms will
      usually resolve with conservative management. However, in a select subgroup of
      patients, the symptoms are refractory to medical management and require more
      invasive therapies. In patients with cervical leaks, EBP in the cervical region
      is an effective management approach, either in close proximity to, or directly
      targeting a dural defect. CT scan-guided cervical EBP is an effective treatment
      approach in refractory SIH, and should be considered in those patients who are
      refractory to conservative management. 

PMID- 26209919
TI  - Predictors of recurrence following resection of intracranial chordomas.
AB  - Management of intracranial chordomas remains challenging, despite improvements in
      microsurgical techniques and radiotherapy. Here, we analyzed the prognostic
      factors associated with improved rates of tumor control in patients with
      intracranial chordomas, who received either gross (GTR) or subtotal resections
      (STR). A retrospective review was performed to identify all patients who were
      undergoing resection of their intracranial chordomas at the Ronald Reagan
      University of California Los Angeles Medical Center from 1990 to 2011. In total,
      57 patients undergoing 81 resections were included. There were 24 females and 33
      males with a mean age of 44.6 years, and the mean tumor diameter was 3.36 cm. The
      extent of resection was not associated with recurrence. For all 81 operations,
      the 1 and 5 year progression free survival (PFS) was 87.5 and 40.4%, and 88.0 and
      33.6% for STR and GTR, respectively (p=0.90). Adjuvant radiotherapy was
      associated with improved rates of PFS (hazard ratio [HR] 0.20; p=0.009).
      Additionally, age >45 years (HR 5.88; p=0.01) and the presence of visual deficits
      (HR 7.59; p=0.03) were associated with worse rates of tumor control. Tumor size,
      sex, tumor histology, and recurrent tumors were not predictors of recurrence.
      Younger age, lack of visual symptoms on presentation and adjuvant radiotherapy
      were associated with improved rates of tumor control following surgery. However,
      GTR and STR produced comparable rates of tumor control. The surgical management
      of intracranial chordomas should take a conservative approach, with the aim of
      maximal but safe cytoreductive resection with adjuvant radiation therapy, and a
      major focus on quality of life.

PMID- 26209920
TI  - Minimally invasive lateral transpsoas approach for spinal discitis and
      osteomyelitis.
AB  - We present a series of patients with discitis and osteomyelitis who were
      surgically treated via a minimally invasive lateral transpsoas approach to the
      lumbar spine. Surgical treatment for spinal discitis and osteomyelitis presents
      challenges because of comorbidities that are common in patients undergoing this
      procedure. A retrospective review found six patients who met strict operative
      criteria including instability, intractable pain, neurological deficit, and
      disease progression. All patients were non-ambulatory before surgery because of
      intractable back pain. The patients underwent standard lateral minimally invasive
      surgery using either the extreme lateral interbody fusion (NuVasive, San Diego,
      CA, USA) or direct lateral interbody fusion (Medtronic Sofamor Danek, Memphis,
      TN, USA) system. The patients underwent debridement with a discectomy and partial
      or complete corpectomy, with polyetheretherketone or titanium cage placement. Two
      patients had additional posterior fixation with percutaneous pedicle screws, and
      none had immediate perioperative complications. The postoperative CT scans
      demonstrated satisfactory debridement and hardware placement. All patients
      experienced significant pain improvement and could ambulate within a few days of
      surgery. So far, the 1 year follow-up data have demonstrated stable hardware with
      solid fusion and continued pain improvements. One patient demonstrated hardware
      failure secondary to refractory infection, 2 months postoperatively, and required
      additional posterior decompression and debridement with pedicle screw fixation.
      The lateral transpsoas approach permits debridement and fixation coupled with
      percutaneous pedicle screw fixation to further stabilize the spine in a minimally
      invasive fashion. Due to the significant comorbidities in this patient
      population, a minimally invasive approach is a suitable surgical technique. A
      close follow-up period is necessary to detect early hardware failure which may
      necessitate more extensive treatment.

PMID- 26209921
TI  - Stereotactic radiosurgery for large brain metastases.
AB  - We evaluated patient outcomes following stereotactic radiosurgery (SRS)-treatment
      of large brain metastasis (?3 cm) at our institution. SRS is an established
      treatment for limited brain metastases. However, large tumors pose a challenge
      for this approach. For this study, 343 patients with 754 total brain metastases
      were treated with SRS, of which 93 had large tumors. The tumor size was 3-3.5,
      3.5-4, and ?4 cm in 29%, 32%, and 39% of these patients. Surgical resection was
      performed prior to SRS in 68% of patients, and 53% achieved a gross total
      resection. The local control of large metastases was inferior compared to smaller
      tumors, with 1 year local control of 68 versus 86%, respectively (p<0.001). Among
      the patients with large metastases, no correlation between local control and
      surgical resection (p=0.747), or extent of surgery (gross total versus subtotal
      resection; p=0.120), was identified. Histology (p=0.939), tumor size (3-4 versus
      >4 cm; p=0.551), and SRS dose (?16 versus >16 Gy; p=0.539) also showed no
      correlation with local failure. The overall survival at 1, 2, and 5 years was
      46%, 29% and 5%, respectively. Prolonged survival was seen in patients with age
      <65 years (p=0.009), primary treatment compared with salvage (p=0.077), and
      controlled primary tumors (p=0.022). Radiation necrosis developed in 10 patients
      (11.8%). For patients with large brain metastases, SRS is well tolerated and can
      achieve local central nervous system disease control in the majority of patients,
      and extended survival in some, though the local control rate is suboptimal.
      Further strategies to improve the outcomes in this subgroup of patients are
      needed.

PMID- 26209922
TI  - Management of flexion distraction injuries to the thoracolumbar spine.
AB  - We present an updated overview of the literature regarding the management of
      flexion distraction injuries (FDI). FDI are unstable fractures of the
      thoracolumbar spine, which require surgical management by long segment open
      fusion or minimally invasive posterior fixation with pedicle screws. While
      associated with concomitant intra-abdominal injuries that may delay operative
      stabilization, FDI frequently involve reversible spinal cord injuries and rapid
      correction is indicated. Modern biomechanical studies have identified valuable
      prognostic indicators that may be elucidated from determining the mechanism of
      injury, including the degree of flexion and presence of compression at the time
      of injury. An improved understanding of FDI will contribute to more appropriate
      diagnoses and treatment of these fractures. 

PMID- 26209923
TI  - Mesenchymal stem cells promote CD206 expression and phagocytic activity of
      macrophages through IL-6 in systemic lupus erythematosus.
AB  - Human umbilical cord-derived mesenchymal stem cells (UCMSCs) show therapeutic
      effects on systemic lupus erythematosus (SLE). Deficiency in functional
      polarization and phagocytosis in macrophages has been suggested in the
      pathogenesis of SLE. We found that macrophages from B6.MRL-Fas(lpr) mice
      exhibited lower level of CD206, the marker for alternatively activated macrophage
      (AAM, also called M2). In addition, the phagocytic activity of B6.MRL-Fas(lpr)
      macrophages was also decreased. UCMSC transplantation improved the proportion of
      CD206(+) macrophages and their phagocytic activity in B6.MRL-Fas(lpr) mice.
      Importantly, macrophages from SLE patients also showed lower expression of CD206
      and reduced phagocytic activity, which were corrected by being co-cultured with
      UCMSCs in vitro and in SLE patients receiving UCMSC transplantation.
      Mechanistically, we demonstrated that IL-6 was required for the up-regulation of
      CD206 expression and phagocytic activity of UCMSC-treated SLE macrophages. Our
      results indicate that UCMSCs alleviate SLE through promoting CD206 expression and
      phagocytic activity of macrophages in an IL-6 dependent manner. 

PMID- 26209924
TI  - Sclerosing epithelioid fibrosarcoma of the thigh: report of two cases with
      synchronous bone metastases.
AB  - We report two cases of sclerosing epithelioid fibrosarcoma occurring in the deep
      soft tissue of the thigh, confirmed by molecular analysis and associated with
      bone metastases in the lumbar vertebrae and the iliac wing at the time of
      diagnosis. Synchronous bone metastases of sclerosing epithelioid fibrosarcoma are
      extremely difficult to diagnose because clinical and radiological features are
      not specific. In addition, the range of differential diagnoses is very wide,
      including metastatic carcinoma and osteosarcoma. At present, all but three
      published cases of sclerosing epithelioid fibrosarcoma with bone metastases
      showed bone metastases during follow-up. We confirm in our two cases that the
      distinct pattern of immunohistochemical staining for MUC4, associated with the
      absence of staining for both SATB2, a marker of osteoblastic differentiation, and
      pan-cytokeratin, allows differentiating between sclerosing epithelioid
      fibrosarcoma and metastatic carcinoma or osteosarcoma. 

PMID- 26209925
TI  - Omega-3 polyunsaturated lipophenols, how and why?
AB  - Polyphenols and n-3 polyunsaturated fatty acids (PUFAs) are two classes of
      natural compounds, which have been highlighted in epidemiological studies for
      their health benefits. The biological activities of those two families of
      metabolites on oxidation, inflammation, cancer, cardiovascular and degenerative
      diseases have been reported in vitro and in vivo. On the other hand, chemical
      bonding between the two structures leading to n-3 lipophenol derivatives (or
      phenolipids) has been studied in numerous works over the last decade, and some
      examples could also be found from natural sources. Interest in lipophilization of
      phenolic structures is various and depends on the domain of interest: in food
      industry, the development of lipidic antioxidants could be performed to protect
      lipidic food matrix from oxidation. Whereas, on pharmaceutical purpose,
      increasing the lipophilicity of polar phenolic drugs could be performed to
      improve their pharmacological profile. Moreover, combining both therapeutic
      aspects of n-3 PUFAs and of polyphenols in a single lipophenolic molecule could
      also be envisaged. An overview of the synthesis and of the natural sources of n-3
      lipophenols is presented here, in addition to their biological activities which
      point out in several cases the benefit of the conjugated derivatives. 

PMID- 26209926
TI  - Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting
      plasma oxytocin and testosterone.
AB  - Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB
      abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We
      measured the effects of GHB on mood, prosocial behavior, social and non-social
      cognition and assessed potential underlying neuroendocrine mechanisms. GHB
      (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled,
      cross-over design. Subjective effects on mood were assessed by visual-analogue
      scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the
      Charity Donation Task, the Social Value Orientation test, and the Reciprocity
      Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood
      plasma levels of GHB, oxytocin, testosterone, progesterone,
      dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic
      hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and
      elicited euphoria, disinhibition, and enhanced vitality. In participants with low
      prosociality, the drug increased donations and prosocial money distributions. In
      contrast, social cognitive abilities such as emotion recognition, empathy, and
      theory-of-mind, and basal cognitive functions were not affected. GHB increased
      plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone,
      DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial
      effects without affecting social hormones such as oxytocin and testosterone.
      These data suggest a potential involvement of GHB-/GABAB-receptors and
      progesterone in mood and prosocial behavior. 

PMID- 26209927
TI  - Clinical outcome and predictive factors of irradiation-associated myasthenia
      gravis exacerbation in thymomatous patients.
AB  - Exacerbations of myasthenia gravis (MG) in patients during radiotherapy for
      thymoma have never been adequately documented. This study aimed to identify
      potential risk factors for the occurrence of MG exacerbation during irradiation
      and to determine whether MG exacerbation during radiotherapy could affect the
      long-term clinical outcome of these patients. A total of 51 thymoma patients with
      MG receiving postoperative radiotherapy from January 2000 to March 2013 were
      retrospectively reviewed. Variables potentially affecting the occurrence of MG
      exacerbation were evaluated using Chi-square test or student's t test. The
      difference in the chance of achieving complete stable remission (CSR),
      pharmacologic remission (PR), and general remission (GR) in the patients with and
      without MG exacerbation was determined by the log-rank test. Fifteen patients
      deteriorated during the irradiation. Univariate analysis showed that the MG
      duration between MG onset and irradiation was significantly longer in patients
      with MG exacerbation than patients without it (p = 0.029). The ratio of patients
      with a history of myasthenic crisis and bulbar symptoms were also higher in
      patients with exacerbation of MG than patients without exacerbation of MG,
      although it did not reach statistic significant. The log-rank test revealed that
      patients without MG exacerbation had higher PR and GR rates (p = 0.017 and p =
      0.009, respectively). The worsening of symptoms appears to be related to the
      longer MG duration and more severe MG before irradiation. Moreover, the patients
      with MG exacerbation had a worse prognosis compared with patients without MG
      exacerbation. Our study highlights the need for preventing the occurrence of MG
      exacerbation in these patients. 

PMID- 26209928
TI  - Intravenous thrombolysis for acute stroke in a patient on treatment with
      rivaroxaban.

PMID- 26209929
TI  - The electrophysiological correlates of the working memory subcomponents: evidence
      from high-density EEG and coherence analysis.
AB  - Synchronization between prefrontal (executive) and posterior (association)
      cortices seems a plausible mechanism for temporary maintenance of information.
      However, while EEG studies reported involvement of (pre)frontal midline
      structures in synchronization, functional neuroimaging elucidated the importance
      of lateral prefrontal cortex (PFC) in working memory (WM). Verbal and spatial WM
      rely on lateralized subsystems (phonological loop and visuospatial sketchpad,
      respectively), yet only trends for hemispheric dissociation of networks
      supporting rehearsal of verbal and spatial information were identified by EEG. As
      oscillatory activity is WM load dependent, we applied an individually tailored
      submaximal load for verbal (V) and spatial (S) task to enhance synchronization in
      the relevant functional networks. To map these networks, we used high-density EEG
      and coherence analysis. Our results imply that the synchronized activity is
      limited to highly specialized areas that correspond well with the areas
      identified by functional neuroimaging. In both V and S task, two independent
      networks of theta synchronization involving dorsolateral PFC of each hemisphere
      were revealed. In V task, left prefrontal and left parietal areas were
      functionally coupled in gamma frequencies. Theta synchronization thus provides
      the necessary interface for storage and manipulation of information, while left
      lateralized gamma synchronization could represent the EEG correlate of the
      phonological loop.

PMID- 26209930
TI  - Repetitive transcranial magnetic stimulation (rTMS) for the treatment of
      depression in Parkinson disease: a meta-analysis of randomized controlled
      clinical trials.
AB  - The objective of this meta-analysis was to evaluate the effects of repetitive
      transcranial magnetic stimulation (rTMS) for the treatment of depression in
      patients with Parkinson disease in order to arrive at qualitative and
      quantitative conclusions about the efficacy of rTMS. We included randomized
      controlled trials examining the effects of rTMS compared with sham-rTMS or
      selective serotonin re-uptake inhibitors (SSRIs). The quality of included studies
      was strictly evaluated. Data analyses were performed using the RevMan5.1
      software. Eight studies including 312 patients met all inclusion criteria. The
      results showed that rTMS could evidently improve the HRSD score compared with
      sham-rTMS (p < 0.00001). However, we found similar antidepressant efficacy
      between rTMS and SSRIs groups in terms of HRSD and BDI score (p = 0.65; p = 0.75,
      respectively). Furthermore, patients who received rTMS could evidently show
      improvement on the unified Parkinson's disease rating scale (UPDRS), ADL score,
      and UPDRS motor score compared with sham-rTMS or SSRIs (p < 0.05, p = 0.05,
      respectively). The subgroup analysis by frequency of rTMS evidenced that the
      efficacy of low-frequency rTMS was superior to sham-rTMS (p < 0.0001) in terms of
      the outcome measure according to HAMD scale. Meanwhile, the high-frequency rTMS
      has the same antidepressant efficacy as SSRIs (p = 0.94). The current meta
      analysis provided evidence that rTMS was superior to sham-rTMS and had similar
      antidepressant efficacy as SSRIs, and may have the additional advantage of some
      improvement in motor function.

PMID- 26209931
TI  - Interferon-beta therapy and risk of thrombocytopenia in multiple sclerosis
      patients.
AB  - Thrombocytopenia is a well-described adverse event of several disease-modifying
      therapies (DMT) in multiple sclerosis (MS). On the other hand, an increased
      prevalence of MS has been reported in patients with immune thrombocytopenia. In
      this retrospective, cross-sectional, case-control study we evaluated in a
      heterogeneous MS cohort: (1) the prevalence of thrombocytopenia in comparison
      with sex- and age-matched controls; (2) the relationship between thrombocytopenia
      and patients' demographic, clinical characteristics; (3) the risk for
      thrombocytopenia in relation to DMT. 187 consecutive MS patients [51 males, mean
      age (+/-SD) 44.5 +/- 10.7 years] and 200 controls (56 males, mean age 45.5 +/- 12
      years) were included. Thrombocytopenia was defined as platelet count lower than
      normal laboratory values (130-400 * 10(9)/L). The prevalence of thrombocytopenia
      was significantly higher in MS patients than in controls (7 vs. 2.5 %, p = 0.04).
      Thrombocytopenia was present only in relapsing-remitting MS cases, and
      significantly associated with lower EDSS (p = 0.002) and with a trend for shorter
      disease duration (p = 0.06). It was more frequent in patients on high-dose
      interferon-beta therapy compared with those on low-dose interferon-beta therapy,
      other therapies or untreated patients (p = 0.02). High-dose interferon-beta
      therapy was associated with more than eightfold increase in the risk for
      thrombocytopenia (odds ratio 8.60, 95 % confidence interval: 1.01-74.48 adjusted
      for EDSS, disease duration and type of disease). The prevalence of
      thrombocytopenia was increased in MS patients treated with DMT. High-dose
      interferon-beta therapy is the variable most strongly associated with
      thrombocytopenia.

PMID- 26209932
TI  - Efficacy of the entomopathogenic fungi Metarhizium anisopliae in the control of
      infestation by stable flies Stomoxys calcitrans (L.), under natural infestation
      conditions.
AB  - The objective of this study was to evaluate the efficacy of an isolate of
      Metarhizium anisopliae applied by aspersion to control of Stomoxys calcitrans
      flies in dairy cattle naturally infested. Was applied by aspersion an aqueous
      formulation of M. anisopliae sensu lato (Ma134), at a concentration of
      1*10(8)conidia/ml, four times with seven day intervals, on a group of eight
      Holstein cows; a control group of eight Holstein cows, received a water solution
      with Tween 80 (0.1%). The average number of flies per animal was estimated one
      day before each application, and then daily counts were done in both groups. The
      effectiveness of the formulation was calculated using the Abbott's formula. At
      the same time, defensive behaviors of stamp/kicks and tail movements were
      evaluated daily, estimating relative frequency per hour. The Ma134 formulation
      had an infestation control efficacy of 73%, taking into consideration the four
      study weeks. The population reduction effect was observed since the first week
      post-application (p<0.05), and the effect increased with the subsequent
      applications. Defensive behaviors were reduced beginning from the first
      application, reaching a reduction of 66% and 70%, respectively, during the four
      weeks of study. These results demonstrated the effectiveness of the formulation
      to control infestation by S. calcitrans, as well as reduce defensive behaviors
      which involves the infestation. 

PMID- 26209933
TI  - Forsythiaside inhibits cigarette smoke-induced lung inflammation by activation of
      Nrf2 and inhibition of NF-kappaB.
AB  - Cigarette smoke has been reported to be the major cause of chronic obstructive
      pulmonary disease (COPD). It causes persistent inflammation by regulating the
      redox-sensitive pathways. Forsythiaside, an active constituent isolated from the
      Chinese medicinal herb Forsythia suspensa, has been reported to have anti
      inflammatory and anti-oxidant effects. Thus, in this study, we investigated the
      protective effects of forsythiaside against cigarette smoke-induced lung
      inflammation in mice. COPD mice model was established by cigarette smoke.
      Forsythiaside was given 2h before cigarette smoke exposure for five consecutive
      days. Bronchoalveolar lavage fluid and lung tissues were collected to assess
      pathological changes, lipid peroxidation, inflammatory cytokine production, Nrf
      2, and NF-kappaB expression. Our results showed that forsythiaside attenuated the
      infiltration of inflammatory cells, NO and inflammatory cytokines TNF-alpha, IL-6
      and IL-1beta production, and reversed the CS-induced decrease of
      glutathione/glutathione disulfide (GSH/GSSG) ratio. Western blot analysis showed
      that forsythiaside inhibited cigarette smoke-induced NF-kappaB activation. In
      addition, forsythiaside dose-dependently up-regulated the expression of Nrf2 and
      HO-1. In conclusion, forsythiaside protected against cigarette smoke-induced lung
      injury through activating Nrf2 and inhibiting NF-kappaB signaling pathway. 

PMID- 26209934
TI  - Renoprotective mechanisms of morin in cisplatin-induced kidney injury.
AB  - In this study, we investigated the renoprotective effects of morin on cisplatin
      induced kidney injury in mice. Serum creatinine and blood urea nitrogen (BUN)
      levels, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) activities
      were determined according to the corresponding kits. The mRNA levels of TNF-alpha
      and IL-1beta in kidney tissues were measured by quantitative real-time PCR (qRT
      PCR). The activities of cytochrome P450 2E1 (CYP2E1), nuclear factor kappa B (NF
      kappaB) p65, P38 mitogen-activated protein kinase (MAPK), Bax, p53 and cleaved
      caspase 3 were evaluated by western blotting. The results showed that the model
      of cisplatin-induced kidney injury was successfully replicated, and morin
      significantly attenuated histopathological changes and decreased the levels of
      TNF-alpha and IL-1beta in the kidneys. In addition, morin attenuated the
      activation of CYP2E1, phospho-NF-kappaB p65, phospho-P38 MAPK, Bax, phospho-p53
      and cleaved caspase 3 in CP-induced kidney injury. In conclusion, these results
      indicated that the renoprotective mechanisms of morin may be attributed to the
      suppression of oxidative stress, inflammation and apoptosis in CP-induced kidney
      injury.

PMID- 26209935
TI  - Generic and eating disorder-specific impairment in binge eating disorder with and
      without overvaluation of weight or shape.
AB  - OBJECTIVE: We sought to elucidate the nature and extent of impairment in quality
      of life among individuals with binge eating disorder (BED) with and without the
      overvaluation of weight or shape ("overvaluation"). METHOD: Subgroups of women -
      probable BED with overvaluation (n = 102), probable BED without overvaluation (n
      = 72), obese individuals reporting no binge eating ("obese control", n = 40), and
      "normal weight" individuals reporting no binge eating ("healthy control," n = 40)
      - were recruited from a community-based sample in which individuals with eating
      disorder symptoms were over-represented. They were compared on measures of eating
      disorder psychopathology and generic and disease-specific measures of quality of
      life. Scores on these measures among individuals with BED receiving specialist
      treatment were also considered. RESULTS: Participants with BED and overvaluation
      had high levels of eating disorder psychopathology and impairment in both generic
      and disease-specific quality of life, comparable to those of BED patients
      receiving specialist treatment, and significantly higher than all other
      subgroups, whereas participants with BED in the absence of overvaluation did not
      differ from obese controls on any of these measures. CONCLUSION: The findings
      provide further evidence for the need to consider reference to overvaluation
      among the diagnostic criteria for BED. The relative merits of the inclusion of
      overvaluation as a diagnostic criterion or as a diagnostic specifier for BED
      warrant greater consideration.

PMID- 26209936
TI  - Cytotoxic diterpenoids from Jatropha curcas cv. nigroviensrugosus CY Yang Roots.
AB  - An investigation of phytochemicals from the roots of Jatropha curcas cv.
      nigroviensrugosus resulted in the isolation of twenty diterpenoids, including
      lathyranlactone, an unusual diterpenoid lactone possessing a 5/13/3 tricyclic
      skeleton, jatrocurcasenones A-E and jatrophodiones B-E, as well as 10 known
      analogues. All isolates were evaluated for cytotoxicity against the HL-60, SMMC
      772, A-549, MCF-7 and SW480 human tumor cell lines using the MTS viability assay.
      Four of the known analogues showed cytotoxic activity in these cell lines, with
      IC50 values ranging from 2.0 to 23.0 MUM. Moreover, the assessment of their
      cytotoxic structure-activity relationships showed the epoxy ring between C-5 and
      C-6 and the hydroxyl group at C-2 were the key functionalities for cytotoxicity.

PMID- 26209937
TI  - Repellency of alpha-pinene against the house fly, Musca domestica.
AB  - Musca domestica L. is a non-biting nuisance fly that is capable of transmitting a
      large variety of pathogens to humans and non-human animals. Natural compounds and
      their derivatives, which are often less toxic than entirely synthetic compounds,
      may be used as repellents against M. domestica as part of comprehensive pest
      control and disease mitigation programs. This work investigates the repellent
      properties of the natural compound alpha-pinene against M. domestica. Adult house
      flies of both sexes avoided the volatile plant-derived terpenes (1S)-(-)-alpha
      pinene 1 and (1R)-(+)-alpha-pinene 2 in constant air flow laboratory conditions,
      with 1 exhibiting a stronger repellent effect. House flies also avoided tarsal
      contact with filter paper saturated with 1. Furthermore, both 1 and 2 are
      electrophysiologically active on in situ female house fly antennal preparations.
      These findings demonstrate that alpha-pinene exhibits natural baseline repellency
      against the house fly, elicits a specific physiological response in this fly, and
      that functional or structural modification of 1 in particular may yield novel fly
      repellents with desirable properties. 

PMID- 26209938
TI  - Variations in Disrupted-in-Schizophrenia 1 gene modulate long-term longitudinal
      differences in cortical thickness in patients with a first-episode of psychosis.
AB  - Schizophrenia patients typically present a widespread bilateral cortical thinning
      from the early stages of the illness. However, there is controversy whether this
      reduction in cortical thickness (CT) is static or progressive over the evolution
      of the disorder. Disrupted-in-Schizophrenia 1 (DISC1) is one of the main
      candidates genes for schizophrenia, as it has been found associated to the
      illness, and to several endophenotypes of the disorder including structural brain
      differences. This gene is known to be involved in neurodevelopment and brain
      maturation processes. We therefore hypothesized that variations in this gene
      modulate different progressions of CT in psychosis. Seventy-nine Caucasian drug
      naive patients experiencing a first episode of non-affective psychosis were
      genotyped for rs6675281 (Leu607Phe) and rs821616 (Ser704Cys) SNPs of the DISC1
      gene. Brain MRIs were carried out at baseline and 3 years after initiating the
      treatment. Other clinical and socio-demographic variables were recorded to rule
      out possible confounding effects. Patients homozygous for the Leu allele of the
      rs6675281 SNP had a significant (p < 0.05) descend in CT over the 3-years period,
      while those carrying the Phe allele presented an increase in CT. When combining
      the two SNPs we found a synergic effect on CT progression, presenting those
      patients homozygous for Leu607 +Ser704 a more pronounced cortical thinning. In
      conclusion, DISC1 gene variations may modulate the longitudinal changes in
      cortical thickness in patients suffering from a first episode of non-affective
      psychosis.

PMID- 26209939
TI  - Incidence of major smoking-related cancers: trends among adults aged 20-44 in
      France from 1982 to 2012.
AB  - BACKGROUND: Tobacco is currently the largest risk factor for cancers of the lung,
      lip/oral cavity/pharynx (LOCP) and esophagus. Variations in tobacco consumption
      over time have led to changes in cancer incidence in the general population. Data
      on the incidence of cancers at these sites in adults aged 20-44 years old are
      scarce. Our objective was to provide estimates of incidence trends for these
      cancers in France among this age group over the last 30 years. METHODS: Observed
      incidence data over the period 1982-2010 for the 20-44 age group were provided
      from six cancer registries (eight for esophagus) covering approximately 6% of the
      French population. Age-period-cohort models were used on the observed period, and
      estimates of cancer incidence for France in 2012 were provided on the basis of
      short-term predictions. RESULTS: In men, a sharp decline was observed over time
      for LOCP and esophageal cancers, while lung cancer saw only a slight decline. In
      women, a large increase was seen in lung cancer incidence, while LOCP cancer
      incidence did not vary significantly. CONCLUSION: Smoking behaviors among adults
      aged 20-44 impact incidence trends in cancers of the lung, LOCP and esophagus,
      although other factors are involved, particularly in LOCP and esophageal cancers.
      Our results highlight the importance of preventative efforts which particularly
      target women aged 20-44. Efforts to curb tobacco smoking in men should also be
      pursued.

PMID- 26209941
TI  - Case of Concurrent MTC and PTC in a Patient with a Germline RET Mutation.

PMID- 26209942
TI  - Depression and anxiety are associated with reduced antiepileptic drug adherence
      in Chinese patients.
AB  - OBJECTIVE: The aim of this study was to investigate the association of depression
      and anxiety with adherence to antiepileptic drugs (AEDs) in Chinese patients with
      epilepsy. METHODS: A total of 184 Chinese patients with epilepsy, and without
      cognitive impairment, underwent psychometric tests: the Beck Depression Inventory
      (BDI) and the Beck Anxiety Inventory (BAI). Adherence to antiepileptic drugs was
      measured by the eight-item Morisky Medication Adherence Scale (MMAS-8). Data on
      patients' demographic characteristics, disease characteristics, and treatment
      characteristics were also collected. RESULTS: The MMAS-8 indicated that 39.7% of
      the patients had low adherence, 34.2% had moderate adherence, and 26.1% had high
      adherence. Demographic, disease, and treatment characteristics were not
      significantly different between the low adherence group and the moderate-to-high
      adherence group. Thirty-six (19.6%) patients had moderate-to-severe depression
      according to the BDI, and 47 (25.5%) patients were considered anxious according
      to the BAI. A significant difference in depression scores was found between the
      low adherence group and the moderate-to-high adherence group (chi(2)=13.625,
      P<0.001). We also found a significant difference in anxiety scores between the
      two groups (chi(2)=8.331, P=0.004). Pearson's correlations indicated that
      depression scores (r=-0.281, P<0.001) and anxiety scores (r=-0.255, P<0.001) were
      negatively correlated with adherence. Negative correlations were found between
      BDI scores and items 2, 7, and 8 of the MMAS-8 (P<0.05); negative correlations
      were also found between BAI scores and items 3 and 6-8 (P<0.05). CONCLUSION:
      Depression and anxiety were associated with reduced antiepileptic drug adherence
      in Chinese patients. Addressing depression and anxiety among patients with
      epilepsy may help improve adherence to AEDs.

PMID- 26209943
TI  - Treatment of refractory generalized status epilepticus in a patient with
      unresponsive wakefulness syndrome: Is neuromodulation the future?

PMID- 26209940
TI  - Nutrition Transition and the Global Diabetes Epidemic.
AB  - Low- and middle-income countries (LMICs) face a rapid change in the nutrition
      transition toward increases in noncommunicable diseases. Underlying this
      transition are shifts in the agricultural system and the subsequent growth of the
      modern retail and food service sectors across all regions and countries, a change
      in technology affecting physical activity and inactivity, mass media access,
      urbanization, and penetration of modern food systems into all societies. The
      resulting major shifts in diet are toward increased refined carbohydrates, added
      sweeteners, edible oils, and animal-source foods and reduced legumes, other
      vegetables, and fruits. Most countries are seeing increases in body mass index
      (BMI), overweight, and waist circumference (WC), and an increased WC-BMI ratio
      appears to be emerging in many regions. The implications of these rapidly
      changing diets and body compositions include the prevalence and severity of
      diabetes in LMICs. 

PMID- 26209944
TI  - Type of preoperative aura may predict postsurgical outcome in patients with
      temporal lobe epilepsy and mesial temporal sclerosis.
AB  - PURPOSE: As the initial symptoms of epileptic seizures, many types of auras have
      significant localizing or lateralizing value. In this study, we hypothesized that
      the type of aura may predict postsurgical outcome in patients with medically
      refractory temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS).
      METHODS: In this retrospective study, all patients with a clinical diagnosis of
      medically refractory TLE due to unilateral mesial temporal sclerosis who
      underwent epilepsy surgery at the Jefferson Comprehensive Epilepsy Center were
      recruited. Patients were prospectively registered in a database from 1986 through
      2014. Postsurgical outcome was classified into two groups: seizure freedom or
      relapse. Outcome was compared between seven groups of patients according to their
      preoperative auras. RESULTS: Two hundred thirty-seven patients were studied. The
      chance of becoming free of seizures after surgery in patients with abdominal aura
      was 65.1%, while in other patients, this was 43.3% (P=0.01). In two-by-two
      comparisons, no other significant differences were observed. CONCLUSION: Patients
      with medically refractory TLE-MTS who reported abdominal auras preceding their
      seizures fared better postoperatively with regard to seizure control compared
      with those who did not report auras, which may indicate bitemporal dysfunction,
      and to patients with other auras, which may indicate a widespread epileptogenic
      zone in the latter group of patients.

PMID- 26209945
TI  - Female sexual dysfunction and epilepsy: It is time for the neurologist to act!

PMID- 26209946
TI  - Behavioral predictors of medication adherence trajectories among youth with newly
      diagnosed epilepsy.
AB  - OBJECTIVE: This study aimed to identify psychosocial predictors of two-year
      antiepileptic drug (AED) adherence trajectories among youth with newly diagnosed
      epilepsy, controlling for known demographic and medical factors. METHOD: This
      study is part of a large, prospective, longitudinal observational study of AED
      adherence and medical outcomes in youth with newly diagnosed epilepsy. Parents
      completed questionnaires of psychosocial and family functioning at one month and
      one year following diagnosis. Chart review and questionnaires were used to
      collect medical variables and seizure outcomes. Previously established two-year
      AED adherence trajectories (Severe Early Nonadherence, Variable Nonadherence,
      Moderate Nonadherence, High Adherence) were used as the outcome variable.
      RESULTS: Participants were 91 parents of youth with epilepsy (7.3+/-2.8years of
      age; 60% male) and their families. Early (one month following diagnosis)
      predictors of two-year adherence trajectories included socioeconomic status,
      epilepsy knowledge, family problem-solving, and family communication. Significant
      predictors one year following diagnosis included socioeconomic status, parent
      fears and concerns, and parent life stress. CONCLUSION: There are modifiable
      parent and family variables that predict two-year adherence trajectories above
      and beyond known medical (e.g., seizures, side effects) factors. Psychosocial
      interventions delivered at key points during the course of epilepsy treatment
      could have a positive impact on adherence outcomes.

PMID- 26209947
TI  - Prevalence and prognostic relevance of cardiac involvement in ANCA-associated
      vasculitis: eosinophilic granulomatosis with polyangiitis and granulomatosis with
      polyangiitis.
AB  - BACKGROUND: To investigate the prevalence and prognostic relevance of cardiac
      involvement in an ANCA-associated vasculitis (AAV) population of eosinophilic
      granulomatosis with polyangiitis (EGPA) and granulomatosis with polyangiitis
      (GPA) patients. METHODS: Prospective cohort study of fifty EGPA and forty-one GPA
      patients in sustained remission without previous in-depth cardiac screening
      attending our clinical immunology outpatient department. Cardiac screening
      included clinical evaluation, ECG, 24-hour Holter registration, echocardiography
      and cardiac magnetic resonance imaging (CMR) with coronary angiography and
      endomyocardial biopsy upon indication. Fifty age-, sex- and cardiovascular risk
      factor-matched control subjects were randomly selected from a population study.
      Long-term outcome was assessed using all-cause and cardiovascular mortality.
      RESULTS: A total of 91 AAV-patients (age 60+/-11, range 63-87years) were compared
      to 50-matched control subjects (age 60+/-9years, range 46-78years). ECG and
      echocardiography demonstrated cardiac abnormalities in 62% EGPA and 46% GPA
      patients vs 20% controls (P<0.001 and P=0.014, respectively). A total of 69 AAV
      patients underwent additional CMR, slightly increasing the prevalence of cardiac
      involvement to 66% in EGPA and 61% in GPA patients. After a mean follow-up of
      53+/-18months, presence of cardiac involvement using ECG and echocardiography in
      AAV-patients showed increased all-cause and cardiovascular mortality (Log-rank
      P=0.015 and Log-rank P=0.021, respectively). CONCLUSION: Cardiac involvement in
      EGPA and GPA patients with sustained remission is high, even if symptoms are
      absent and ECG is normal. Moreover, cardiac involvement is a strong predictor of
      (cardiovascular) mortality. Therefore, risk stratification using cardiac imaging
      is recommended in all AAV-patients, irrespective of symptoms or ECG
      abnormalities.

PMID- 26209948
TI  - Management of concomitant coronary artery disease in patients undergoing
      transcatheter aortic valve implantation: the United Kingdom TAVI Registry.
AB  - BACKGROUND: The management and impact of concomitant coronary artery disease in
      patients referred for TAVI remains contentious. We describe the prevalence,
      clinical impact and management of coronary artery disease (CAD) in patients in
      the United Kingdom TAVI Registry. METHODS: All-inclusive study of patients
      undergoing TAVI in the United Kingdom (excluding Northern Ireland) from January
      2007 to December 2011. Coronary artery disease at the time of TAVI was
      demonstrated on invasive angiography. RESULTS: 2588 consecutive patients were
      entered in the U.K. TAVI Registry. CAD was reported in 1171 pts with left main
      stem involvement in 12.4% of this cohort (n=145). Most patients were free of
      chest pain, but limited by dyspnoea (NYHA Class III & IV 81.9%). Angina was
      however more prevalent in those patients with CAD (p<0.0001). Hybrid PCI was
      uncommon, performed in only 14.7% of the CAD cohort (n=172). Survival at 30days,
      1year, and 4years was 93.7%, 81.4% and 72.0% respectively. Adjusting for
      confounders in a multivariate model the presence and extent of CAD was not
      associated with early (30-days, p=0.36) or late (4years, p=0.10) survival.
      CONCLUSIONS: This contemporary study of coronary artery disease management in an
      "all-comers" patient population undergoing TAVI demonstrates that whilst often an
      indicator of significant underlying comorbidity coronary artery disease is not
      associated with decreased short or long-term survival. The majority of patients
      with aortic stenosis and concomitant CAD can be managed effectively by TAVI
      alone. However, the importance of the Heart Team in making decisions on
      individual patients must not be underestimated.

PMID- 26209949
TI  - Diagnostic accuracy of the Catheter Injection and Aspiration (CINAS)
      classification for assessing the function of totally implantable venous access
      devices.
AB  - PURPOSE: Intravenous catheters are used for the administration of intravenous
      therapy and for blood sampling. These devices are considered as well-functioning
      if both the injection and aspiration are easy. Malfunction is frequently observed
      and usually vaguely described as occlusion. We developed the CINAS, the Catheter
      Injection and Aspiration scheme. The CINAS is a catheter function classification
      tool, which classifies both the injection and the aspiration ability in a uniform
      way. Each CINAS class consists of a combination of an injection (IN) and an
      aspiration (AS) code: e.g. IN1AS1 is the CINAS class for a well-functioning
      catheter. In this series, we aimed to determine the accuracy of the CINAS class
      reported by nurses, after minimal training, versus a trained researcher, acting
      as a reference standard. METHODS: Catheter function was assessed during a
      standard blood sampling procedure through a totally implantable venous access
      device in a convenience sample of 150 oncology patients. One nurse researcher and
      111 oncology nurses both scored the catheter function according to the CINAS
      classification scheme, independently. Concordance between the scores was
      calculated. RESULTS: For the 140 catheters scored as well-functioning (IN1AS1
      score) by the researcher, 139 or 99.3 % (95 % confidence interval (CI) 96.1-99.9
      %) were scored correctly by the nurse participants. Nine out of ten or 90 % (95 %
      CI 55.5-98.3 %) of malfunctioning catheters (researcher scores different from
      IN1AS1) were also identified as malfunctioning by the nurse participants and
      received exactly the same CINAS score in eight cases (80 %, 95 % CI 44.4-97.5 %).
      The overall accuracy of the CINAS scored by the nurse participants versus the
      researcher is (139 + 9)/150 or 98.7 % (95 % CI 95.3-99.8 %). CONCLUSIONS: Nurse
      participants were able to classify the catheter function of totally implantable
      venous access devices with the CINAS accurately after a brief explanation about
      the classification options.

PMID- 26209950
TI  - Inadequate pain management in cancer patients attending an outpatient palliative
      radiotherapy clinic.
AB  - PURPOSE: The aim of this study is to assess the prevalence of undertreated cancer
      pain in an outpatient palliative radiotherapy clinic using the Pain Management
      Index (PMI). METHODS: A retrospective analysis of a prospective database to
      assess pain management was done on patients with cancer pain enrolled from
      January 2009 to March 2015 using recorded pain intensity (0-10) and baseline pain
      medications. The pain intensities were categorized into no pain (0), mild pain
      (1), moderate pain (2), and severe pain (3), and an analgesic score was assigned
      to the most potent pain medication the patient was taking during the time of data
      collection. "0" was assigned to no analgesics, "1" to non-opioids, "2" to weak
      opioids, and "3" for strong opioids based on the WHO guidelines. The PMI was
      calculated for each patient by subtracting the pain score from the analgesic
      score. A negative value indicated undertreatment, and a value of 0 or greater
      corresponded to adequate pain management. RESULTS: Three hundred fifty-four
      patients were included in the study. The incidence of inadequate pain management
      was 33.3 %, similar to that reported in our previous studies. Additionally, 106
      patients were taking strong opioids and reporting severe pain despite being the
      PMI reporting adequately treated. CONCLUSION: The rate of undertreatment is
      similar to that reported in past studies; however, the rates have shown a slight
      increase in our palliative radiotherapy clinic since the last assessment.
      Inadequate management of cancer pain continues to be a problem.

PMID- 26209951
TI  - Vascular entrapment of the sciatic plexus causing catamenial sciatica and urinary
      symptoms.
AB  - AIM OF THE VIDEO / INTRODUCTION: Pelvic congestion syndrome is a well-known cause
      of cyclic pelvic pain (Ganeshan et al., Cardiovasc Intervent Radiol 30(6):1105
      11, 2007). What is much less well known is that dilated or malformed branches of
      the internal or external iliac vessels can entrap the nerves of the sacral plexus
      against the pelvic sidewalls, producing symptoms that are not commonly seen in
      gynecological practice, such as sciatica, or refractory urinary and anorectal
      dysfunction (Possover et al., Fertil Steril 95(2):756-8. 2011). The objective of
      this video is to explain and describe the symptoms suggestive of vascular
      entrapment of the sacral plexus, as well as the technique for the laparoscopic
      decompression of these nerves. METHOD: Two anecdotal cases of intrapelvic
      vascular entrapment are used to review the anatomy of the lumbosacral plexus and
      demonstrate the laparoscopic surgical technique for decompression at two
      different sites, one on the sciatic nerve and one on the sacral nerve roots.
      RESULT: After surgery, the patient with the sciatic entrapment showed full
      recovery of the sciatica and partial recovery of the myofascial pain. The patient
      with sacral nerve root entrapment showed full recovery with resolution of
      symptoms. CONCLUSION: The symptoms suggestive of intrapelvic nerve entrapment
      are: perineal pain or pain irradiating to the lower limbs in the absence of a
      spinal disorder, and lower urinary tract symptoms in the absence of prolapse of a
      bladder lesion. In the presence of such symptoms, the radiologist should provide
      specific MRI sequences of the intrapelvic portion of the sacral plexus and a team
      and equipment to expose and decompress the sacral nerves should be prepared.

PMID- 26209952
TI  - Polyacrylamide hydrogel (Bulkamid(r)) for stress urinary incontinence in women: a
      systematic review of the literature.
AB  - INTRODUCTION AND HYPOTHESIS: Polyacrylamide hydrogel (PAHG, Bulkamid(r)) is one
      of several injectable agents currently used for the treatment of women with
      urinary stress incontinence. Although bulking agents appear to have lower
      efficacy rates compared to other surgical treatments, current evidence based on
      large prospective or comparative studies as well as systematic reviews is
      limited. The purpose of this study was to conduct a systematic review on the
      efficacy of PAHG in the treatment of female patients with stress urinary
      incontinence with regard to reproducibility, feasibility, safety and clinical
      outcome. METHODS: We searched MEDLINE (1966-2015), Scopus (2004-2015), POPLINE
      (1974-2015) and ClinicalTrials.gov (2008-2015) along with reference lists of
      electronically retrieved studies. Observational studies, prospective,
      retrospective and randomized controlled studies were included. Two reviewers
      independently selected studies, assessed the risk of bias and tabulated data to
      structured forms. RESULTS: We included 8 studies, which enrolled a total of 767
      patients who received treatment with PAHG. We found that 186 of 767 women (24.3
      %, range 12-35 %) required reinjection in order to achieve adequate efficacy. The
      most frequent adverse effects were pain at the site of injection (4-14 %) and
      urinary tract infections (3-7 %). Both the number of incontinence episodes/24 h
      and the number of ml/24 h were significantly reduced 1 year following treatment
      and the quality of life of patients was significantly improved. CONCLUSIONS: PAHG
      is a safe intervention for treating women with stress urinary incontinence, but
      repeat injections are often required. Further research is mandated in the field
      in order to compare its efficacy to other bulking agents.

PMID- 26209953
TI  - Reliability and validity of the Turkish King's Health Questionnaire in women with
      urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to translate the King's
      Health Questionnaire (KHQ) into Turkish and to test its reliability and validity
      among Turkish women with urinary incontinence (UI). METHODS: Three hundred and
      thirty-five women with symptoms of UI completed the Turkish versions of the KHQ,
      short forms of the Urogenital Distress Inventory (UDI-6) and Incontinence Impact
      Questionnaire (IIQ-7), and the Incontinence Severity Index (ISI). Psychometric
      analysis of the KHQ included assessments of test-retest reliability, internal
      consistency, construct, and criterion validity. Factor analysis was used to
      explore the underlying structure of the KHQ. RESULTS: The internal consistency
      (Cronbach's alpha >=0.68) and test-retest reliability of the KHQ were found to be
      high (p < 0.001). Interdomain correlation analysis showed good convergent
      validity among Role, Physical, and Social Limitations, with relatively higher
      correlations and divergent validity between Personal Relationships and other
      domains, with relatively lower correlations. Exploratory factor analysis
      identified three factors, namely, Daily Life and Emotions, Personal Relationship,
      and General Health Perception. The KHQ was also significantly correlated with IIQ
      7, UDI-6, and ISI (p < 0.01). CONCLUSIONS: The results suggest that the Turkish
      KHQ is a valid and reliable condition-specific quality of life instrument for
      Turkish women with UI.

PMID- 26209954
TI  - MRI of female urethra and periurethral pathologies.
AB  - INTRODUCTION AND HYPOTHESIS: Accurate diagnosis of a wide spectrum of
      urethral/periurethral pathologies in women remains challenging due to its
      anatomical location and nonspecific clinical presentations. Magnetic resonance
      imaging (MRI) has emerged as the modality of choice for diagnosing female
      urethral and periurethral pathologies due to its multiplanar scanning capability,
      superior soft tissue differentiation, noninvasive nature, and overall excellent
      contrast resolution. METHODS: In this narrative review, we describe the use of
      MRI to visualize the female urethra and periurethral pathologies. RESULTS: MRI
      can confidently characterize lesions into cystic or solid, provide a more
      succinct differential diagnosis, and in some cases provide a specific and
      accurate diagnosis, enabling surgeons to prepare a roadmap before operative
      procedure. Moreover, functional MRI can be useful to assess dynamic disorders
      such as urethral hypermobility. CONCLUSIONS: We provide a comprehensive review of
      normal MR anatomy of the female urethra, as well as the MR features of
      practically important urethral and periurethral lesions.

PMID- 26209955
TI  - Biomarker- versus drug-driven tumor growth inhibition models: an equivalence
      analysis.
AB  - The mathematical modeling of tumor xenograft experiments following the dosing of
      antitumor drugs has received much attention in the last decade. Biomarker data
      can further provide useful insights on the pathological processes and be used for
      translational purposes in the early clinical development. Therefore, it is of
      particular interest the development of integrated pharmacokinetic-pharmacodynamic
      (PK-PD) models encompassing drug, biomarker and tumor-size data. This paper
      investigates the reciprocal consistency of three types of models: drug-to-tumor,
      such as established drug-driven tumor growth inhibition (TGI) models, drug-to
      biomarker, e.g. indirect response models, and biomarker-to-tumor, e.g. the more
      recent biomarker-driven TGI models. In particular, this paper derives a
      mathematical relationship that guarantees the steady-state equivalence of the
      cascade of drug-to-biomarker and biomarker-to-tumor models with a drug-to-tumor
      TGI model. Using the Simeoni TGI model as a reference, conditions for steady
      state equivalence are worked out and used to derive a new biomarker-driven model.
      Simulated and real data are used to show that in realistic cases the steady-state
      equivalence extends also to transient responses. The possibility of predicting
      the drug-to-tumor potency of a new candidate drug based only on biomarker
      response is discussed. 

PMID- 26209956
TI  - A pharmacometric case study regarding the sensitivity of structural model
      parameter estimation to error in patient reported dosing times.
AB  - Although there is a body of literature focused on minimizing the effect of dosing
      inaccuracies on pharmacokinetic (PK) parameter estimation, most of the work
      centers on missing doses. No attempt has been made to specifically characterize
      the effect of error in reported dosing times. Additionally, existing work has
      largely dealt with cases in which the compound of interest is dosed at an
      interval no less than its terminal half-life. This work provides a case study
      investigating how error in patient reported dosing times might affect the
      accuracy of structural model parameter estimation under sparse sampling
      conditions when the dosing interval is less than the terminal half-life of the
      compound, and the underlying kinetics are monoexponential. Additional effects due
      to noncompliance with dosing events are not explored and it is assumed that the
      structural model and reasonable initial estimates of the model parameters are
      known. Under the conditions of our simulations, with structural model CV %
      ranging from ~20 to 60 %, parameter estimation inaccuracy derived from error in
      reported dosing times was largely controlled around 10 % on average. Given that
      no observed dosing was included in the design and sparse sampling was utilized,
      we believe these error results represent a practical ceiling given the
      variability and parameter estimates for the one-compartment model. The findings
      suggest additional investigations may be of interest and are noteworthy given the
      inability of current PK software platforms to accommodate error in dosing times.

PMID- 26209957
TI  - Pediatric ovarian torsion: a pictorial review.
AB  - Imaging is crucial in expediting the diagnosis and guiding definitive therapy in
      children with ovarian torsion. This article reviews the multimodality spectrum of
      imaging findings in pediatric ovarian torsion, focusing primarily on US
      appearances. We describe predisposing conditions that can lead to torsion, the
      pathological basis of the radiologic findings in ovarian torsion, and the common
      diagnostic pitfalls. 

PMID- 26209958
TI  - Comparison of early and late MRI in neonatal hypoxic-ischemic encephalopathy
      using three assessment methods.
AB  - BACKGROUND: There is no consensus on the optimum timing of MRI in neonates with
      hypoxic-ischemic encephalopathy treated with hypothermia. Reliable early imaging
      assessment might help managing treatment. OBJECTIVE: To assess non-random
      differences between early and late MRI that might influence intensive-care
      decisions. MATERIALS AND METHODS: This single-center retrospective study included
      all asphyxiated term neonates eligible for hypothermia treatment November 2009
      July 2012. MRI scans were systematically performed at day 4 (early MRI) and day
      11 of life as part of routine protocol. Two experienced pediatric radiologists
      reviewed both scans according to three assessment methods: a pattern
      classification, a scoring system and a simplified classification. Agreement
      between early and late imaging findings was assessed using Cohen's kappa
      coefficients. RESULTS: Thirty-three neonates were included. Interobserver
      agreement was excellent. Early MRI detected all severe injuries. Agreement
      between early and late MRI was excellent for the simplified classification (kappa
      = 0.82), good for the pattern classification (kappa = 0.64), and good to
      excellent for 3 scores out of 4 in the scoring system (kappa = 0.70-0.89).
      CONCLUSION: Early MRI may provide valuable information about brain injury to help
      parents and neonatologists in intensive-care decisions at the end of hypothermia
      treatment.

PMID- 26209959
TI  - Carpal erosions in children with juvenile idiopathic arthritis: repeatability of
      a newly devised MR-scoring system.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is characterized by synovial
      inflammation, with potential risk of developing progressive joint destruction.
      Personalized state-of-the-art treatment depends on valid markers for disease
      activity to monitor response; however, no such markers exist. OBJECTIVE: To
      evaluate the reliability of scoring of carpal bone erosions on MR in children
      with JIA using two semi-quantitative scoring systems. MATERIALS AND METHODS: A
      total of 1,236 carpal bones (91 MR wrist examinations) were scored twice by two
      independent pediatric musculoskeletal radiologists. Bony erosions were scored
      according to estimated bone volume loss using a 0-4 scale and a 0-10 scale. An
      aggregate erosion score comprising the sum total carpal bone volume loss was
      calculated for each examination. RESULTS: The 0-4 scoring system resulted in good
      intra-reader agreement and moderate to good inter-observer agreement in the
      assessment of individual bones. Fair and moderate agreement were achieved for
      inter-reader and intra-reader agreement, respectively, using the 0-10 scale.
      Intra- and particularly inter-reader aggregate score variability were much less
      favorable, with wide limits of agreement. CONCLUSION: Further analysis of erosive
      disease patterns compared with normal subjects is required, and to facilitate the
      development of an alternative means of quantifying disease.

PMID- 26209960
TI  - De novo radiologic placement of button gastrostomy: a feasibility study in
      children with cancer.
AB  - BACKGROUND: Primary placement of percutaneous radiologic button gastrostomy has
      been successfully performed in adults but research is lacking as to its success
      in children during cancer treatment. OBJECTIVE: To assess the safety and
      effectiveness of such treatment at a single center. MATERIALS AND METHODS: We
      conducted a 3-year retrospective feasibility study reporting on placement
      procedure, feeding plan, acute complications and effectiveness of this technique
      based on the evolution of the weight and weight-to-height during a period of 3
      months. RESULTS: Eleven gastrostomies were performed in 11 children and young
      adults (3-20 years old) during oncological treatment. No major complications
      occurred. Two patients experienced minor side effects -- local leakage and
      granulation tissue formation -- both easily treated. In all cases, enteral
      feeding started within 24 h following the button placement. The patients were
      able to go home within 72 h. After 1 month, 64% (7/11) had gained weight, 18%
      (2/11) had maintained weight and 9% (1/11) had lost weight. After 3 months, 73%
      (8/11) had gained weight and 9% (1/11) had lost weight. CONCLUSION: The procedure
      and devices were well tolerated and mostly effective in our cohort.

PMID- 26209961
TI  - Volvulus of the entire small bowel with normal bowel fixation simulating
      malrotation and midgut volvulus.
AB  - BACKGROUND: Midgut volvulus is a complication of malrotation of bowel and
      mesenteric malfixation. In contrast, primary volvulus of the small bowel is a
      distinctly different and rare entity characterized by torsion of the entire small
      bowel with normal mesenteric fixation. OBJECTIVE: To present the clinical and
      imaging findings in four infants with primary small bowel volvulus and normal
      bowel fixation in order to improve awareness of this entity among clinicians and
      radiologists and to discuss the potential etiologies of this entity to
      distinguish it from other causes of small bowel volvulus. MATERIALS AND METHODS:
      A retrospective review of imaging studies (two ultrasounds and four upper
      gastrointestinal series) in four infants (three full-term and one premature) from
      three institutions with surgically proven volvulus of the entire small bowel and
      normal bowel fixation were reviewed by three board-certified pediatric
      radiologists and correlated with clinical and surgical reports when available.
      RESULTS: The infants presented during the first week to 6 months of life and were
      acutely ill. The upper gastrointestinal series showed complete duodenal
      obstruction with beaking in one and partial duodenal obstruction in three. All
      studies were interpreted as highly suspicious for malrotation and midgut
      volvulus. Emergent laparotomy demonstrated primary small bowel volvulus with
      normal mesenteric fixation in all infants. The base of the small bowel mesentery
      was described by the operating surgeon as smaller than normal in one infant (case
      3). There was no mesenteric defect or other abnormality predisposing to volvulus
      in the other three. In both infants who had abdominal US, a retroperitoneal
      position of the third portion of the duodenum was demonstrated. All infants
      survived. One infant required resection of the necrotic small bowel and currently
      has short gut syndrome, one has malabsorption and two were lost to follow-up.
      CONCLUSION: Primary small bowel volvulus with normal fixation is
      indistinguishable from malrotation with midgut volvulus in the acutely ill infant
      or child. Radiographic diagnosis can be difficult in patients with intermittent
      or incomplete small bowel volvulus without malrotation. In these patients,
      neither an upper gastrointestinal series demonstrating a normal position of the
      duodenojejunal junction nor the sonographic demonstration of a retromesenteric
      third portion of the duodenum excludes the diagnosis. In young infants, the
      clinical and imaging findings may mimic necrotizing enterocolitis. Sonography may
      be useful to evaluate the bowel for signs of bowel wall compromise or a whirlpool
      sign.

PMID- 26209962
TI  - A bipolar II cohort (ABC): The association of functional disability with gender
      and rapid cycling.
AB  - BACKGROUND: Bipolar II disorder (BP II) is a chronic, frequently co-morbid, and
      complex disorder with similar rates of attempted suicide to BP I. However, case
      identification for BP II studies that is based on clinician diagnosis alone is
      prone to error. This paper reports on differences between clinical and research
      diagnoses and then describes the clinical characteristics of a carefully defined
      BP II cohort. METHODS: A cohort of rigorously defined BP II cases were recruited
      from a range of primary and secondary health services in the North of England to
      participate in a programme of cross-sectional and prospective studies. Case
      identification, and rapid cycling, comorbidities and functioning were examined.
      RESULTS: Of 355 probable clinical cases of BP II disorder, 176 (~50%) met
      rigorous diagnostic criteria. The sample mean age was ~44 years, with a mean
      duration of mood disorder of ~18 years. Two thirds of the cohort were female
      (n=116), but only 40% were in paid employment. Current and past year functioning
      was more impaired in females and those with rapid cycling. LIMITATIONS: This
      paper describes only the preliminary assessments of the cohort, so it was not
      possible to examine additional factors that may contribute to the explained
      variance in functioning. CONCLUSIONS: This carefully ascertained cohort of BP II
      cases show few gender differences, except for levels of functional impairment.
      Interestingly, the most common problem identified with using case note diagnoses
      of BP II arose because of failure to record prior episodes of mania, not failure
      to identify hypomania.

PMID- 26209963
TI  - Chitosan coated nanostructured lipid carriers for brain delivery of proteins by
      intranasal administration.
AB  - The remarkable increase in the prevalence of neurodegenerative diseases has
      become a serious public health problem. Considering the lack of effective
      treatments to address these diseases and the difficulties in accessing the brain
      due to the blood-brain barrier (BBB), to attain a successful strategy to improve
      drug delivery to the brain, the administration route becomes a point of interest.
      The intranasal route provides a non-invasive method to bypass the BBB. Moreover,
      the development of new technologies for the protection and delivery of peptides
      is an interesting approach to consider. Thus, in this work, a suitable chitosan
      coated nanostructured lipid carrier (CS-NLC) formulation with the capacity to
      reach the brain after being intranasally administered was successfully developed
      and optimized. The optimal formulation displayed a particle size of 114 nm with a
      positive surface charge of +28 mV. The in vitro assays demonstrated the
      biocompatibility of the nanocarrier and its cellular uptake by 16HBE14o- cells.
      Furthermore, no haemagglutination or haemolysis processes were observed when the
      particles were incubated with erythrocytes, and no toxicity signals appeared in
      the nasal mucosa of mice after the administration of CS-NLCs. Finally, the
      biodistribution study of CS-NLC-DiR demonstrated an efficient brain delivery of
      the particles after intranasal administration. In conclusion, CS-NLC can be
      considered to be a safe and effective nanocarrier for nose-to-brain drug
      delivery; however, to obtain a higher concentration of the drug in the brain
      following intranasal administration, further modifications are warranted in the
      CS-NLC formulation.

PMID- 26209964
TI  - Bioconjugation of gold-polymer core-shell nanoparticles with bovine serum amine
      oxidase for biomedical applications.
AB  - Core-shell gold nanoparticles [AuNPs], stabilized with a hydrophilic polymer,
      poly(3-dimethylammonium-1-propyne hydrochloride) [PDMPAHCl], have been used for
      the immobilization of bovine serum amine oxidase [BSAO]. The functionalized
      surface of the hybrid nanoparticles is pH responsive, due to the presence of
      aminic groups that carry out a double role: on one hand they act as ligands for
      the gold nanoparticle surface, allowing the colloidal stabilization and, on the
      other hand, they give a hydrophilic characteristic to the whole colloidal
      suspension. The core-shell nanoparticles [Au@PDMPAHCl] have been characterized by
      using UV-vis and X-ray photoelectron spectroscopy, DLS, zeta-potential
      measurements and by FE-TEM microscopy. BSAO enzyme can be loaded by non-covalent
      immobilization onto Au@PDMPAHCl nanoparticles up to 70% in weight, depending on
      the pH values of the environmental medium. Activity tests on Au@PDMPAHCl-BSAO
      bioconjugates confirm an enzymatic activity up to 40%, with respect to the free
      enzyme activity. Moreover, our results show that loading and enzymatic activity
      are rather interrelated characteristics and that, under appropriate polymer
      concentration and pH conditions, a satisfactory compromise can be reached. These
      results, as a whole, indicate that Au@PDMPAHCl-BSAO bioconjugate systems are
      promising for future biomedical applications. 

PMID- 26209965
TI  - Pendant small functional groups on poly(epsilon-caprolactone) substrate modulate
      adhesion, proliferation and differentiation of human mesenchymal stem cells.
AB  - Probing stem cell-biomaterial interactions is of great significance in both
      gaining profound understanding of stem cell biology and advancing tissue
      regeneration. In the present work, we developed a series of poly(epsilon
      caprolactone) (PCL) films bearing distinct pendant small functional groups to
      study the effects of biomaterial substrate chemistry on stem cell behaviors. PCL
      films, bearing hydroxyl (OH), methyl (CH3), carboxyl (COOH) and amino (NH2),
      demonstrated varied surface properties, such as wettability, serum protein
      adsorption and surface topographical feature. In comparison with pristine PCL
      film, the adhesion of hMSCs on PCL-COOH, PCL-OH and PCLCO films was significantly
      promoted and cells slightly outgrew on PCL-NH2 and PCL-COOH films. Most
      importantly, the tri-lineage differentiation of hMSCs varied on this series of
      PCL films, with the best osteogenesis achieved on PCL-NH2 film, PCL and PCL-CH3
      films supporting the superior adipogenic differentiation and PCL-CH3 film being
      the most favorable one for chondrogenesis. This study highlights the critical
      roles of surface chemistry in modulating the fates of MSCs and potentially
      provides a practical guidance in developing instructive tissue engineering
      scaffolds.

PMID- 26209966
TI  - Impacts of pH-mediated EPS structure on probiotic bacterial pili-whey proteins
      interactions.
AB  - Probiotic bacteria are routinely incorporated into dairy foods because of the
      health benefits they can provide when consumed. In this work, the marked pH
      dependence of the pili/EPS organization at the outer surface of Lactobacillus
      rhamnosus GG is characterized in detail by Single Cell Force Microscopy and cell
      electrophoretic mobility measurements analyzed according to formalisms for
      nanomechanical contact and soft particle electrokinetics, respectively. At pH
      6.8, LGG pili are easily accessible by AFM tips functionalized with whey proteins
      for specific binding, while at pH 4.8 the collapsed EPS surface layer
      significantly immobilized the LGG pili. This resulted in their reduced
      accessibility to the specific whey-coated AFM tip, and to stronger whey protein
      pili rupture forces. Thus, pili interactions with whey proteins are screened to
      an extent that depends on the pH-mediated embedment of the pili within the EPS
      layer. 

PMID- 26209967
TI  - Bio-inspired mineralization of hydroxyapatite in 3D silk fibroin hydrogel for
      bone tissue engineering.
AB  - To fabricate hard tissue implants with bone-like structure using a biomimetic
      mineralization method is drawing much more attentions in bone tissue engineering.
      The present work focuses in designing 3D silk fibroin hydrogel to modulate the
      nucleation and growth of hydroxyapatite crystals via a simple ion diffusion
      method. The study indicates that Ca(2+) incorporation within the hydrogel
      provides the nucleation sites for hydroxyapatite crystals and subsequently
      regulates their oriented growth. The mineralization process is regulated in a
      Ca(2+) concentration- and minerlization time-dependent way. Further, the
      compressive strength of the mineralized hydrogels is directly proportional with
      the mineral content in hydrogel. The orchestrated organic/inorganic composite
      supports well the viability and proliferation of human osteoblast cells; improved
      cyto-compatibility with increased mineral content. Together, the present
      investigation reports a simple and biomimetic process to fabricate 3D bone-like
      biomaterial with desired efficacy to repair bone defects. 

PMID- 26209968
TI  - Cardiogenic differentiation of mesenchymal stem cells with gold nanoparticle
      loaded functionalized nanofibers.
AB  - Cardiac tissue engineering promises to revolutionize the treatment of patients
      with end-stage heart failure and provide new solutions to the serious problems of
      shortage of heart donors. The influence of extracellular matrix (ECM) plays an
      influential role along with nanostructured components for guided stem cell
      differentiation. Hence, nanoparticle embedded Nanofibrous scaffolds of FDA
      approved polycaprolactone (PCL), Vitamin B12 (Vit B12), Aloe Vera(AV) and Silk
      fibroin(SF) was constructed to differentiate mesenchymal stem cells into cardiac
      lineage. Cardiomyocytes (CM) and Mesenchymal stem cells (MSC) were co-cultured on
      these fabricated nanofibrous scaffolds for the regeneration of infarcted
      myocardium. Results demonstrated that synthesized gold nanoparticles were of the
      size 16 nm and the nanoparticle loaded nanofibrous scaffold has a mechanical
      strength of 2.56 MPa matching that of the native myocardium. The gold
      nanoparticle blended PCL scaffolds were found to be enhancing the MSCs
      proliferation and differentiation into cardiogenesis. Most importantly the
      phenotype and cardiac marker expression in differentiated MSCs were highly
      resonated in gold nanoparticle loaded nanofibrous scaffolds. The appropriate
      mechanical strength provided by the functionalized nanofibrous scaffolds
      profoundly supported MSCs to produce contractile proteins and achieve typical
      cardiac phenotype.

PMID- 26209969
TI  - Cryptic speciation in the Acari: a function of species lifestyles or our ability
      to separate species?
AB  - There are approximately 55,000 described Acari species, accounting for almost
      half of all known Arachnida species, but total estimated Acari diversity is
      reckoned to be far greater. One important source of currently hidden Acari
      diversity is cryptic speciation, which poses challenges to taxonomists
      documenting biodiversity assessment as well as to researchers in medicine and
      agriculture. In this review, we revisit the subject of biodiversity in the Acari
      and investigate what is currently known about cryptic species within this group.
      Based on a thorough literature search, we show that the probability of occurrence
      of cryptic species is mainly related to the number of attempts made to detect
      them. The use of, both, DNA tools and bioassays significantly increased the
      probability of cryptic species detection. We did not confirm the generally
      accepted idea that species lifestyle (i.e. free-living vs. symbiotic) affects the
      number of cryptic species. To increase detection of cryptic lineages and to
      understand the processes leading to cryptic speciation in Acari, integrative
      approaches including multivariate morphometrics, molecular tools, crossing,
      ecological assays, intensive sampling, and experimental evolution are
      recommended. We conclude that there is a demonstrable need for future
      investigations focusing on potentially hidden mite and tick species and
      addressing evolutionary mechanisms behind cryptic speciation within Acari.

PMID- 26209970
TI  - Steroid responsive encephalopathy associated with autoimmune thyroiditis
      following ipilimumab therapy: a case report.
AB  - BACKGROUND: Ipilimumab is a cytotoxic T-lymphocyte-associated protein 4 receptor
      antibody used for immunotherapy in cancer. Several immune-related adverse events
      are known. Steroid responsive encephalopathy associated with autoimmune
      thyroiditis is an autoimmune encephalopathy associated with Hashimoto's Disease
      and elevated serum levels of the related antibodies (anti-thyroid-peroxidase
      antibody or anti-thyroglobulin antibody). Our case implies that steroid
      responsive encephalopathy associated with autoimmune thyroiditis may be another
      previously unreported side effect of ipilimumab therapy. CASE PRESENTATION: We
      report the case of a 64 years old caucasian patient with prostatic cancer who
      received ipilimumab therapy in a clinical trial. He presented with aphasia,
      tremor and ataxia, myocloni, hallucinations, anxiety and agitation in turns with
      somnolence. Cranial nerves, deep tendon reflexes, motor and sensory functions
      were normal. Electroencephalography showed background slowing but no epileptic
      discharges. Brain magnetic resonance imaging was normal and showed no signs of
      hypophysitis. Cerebrospinal fluid findings ruled out infection and neoplastic
      meningitis. Anti-thyroid antibodies (anti-thyroid-peroxidase antibody and anti
      thyroglobulin antibody) were heavily increased. Assuming steroid responsive
      encephalopathy associated with autoimmune thyroiditis the patient was treated
      with 1,000 mg methylprednisolone i.v. for 3 days and continued with 1 mg/kg
      orally. On the 3rd day of treatment the patient's condition started to improve.
      Within the next few days he gradually returned to his previous state, and
      electroencephalography eventually showed only slight slowing. Seven months later
      the patient's condition was stable, and anti-thyroid antibodies were no more
      detectable. CONCLUSION: Steroid responsive encephalopathy associated with
      autoimmune thyroiditis may be a hitherto unrecognized complication of ipililumab
      treatment and should be taken into consideration in patients developing central
      nervous symptoms undergoing this treatment.

PMID- 26209971
TI  - Sequencing of superficial trunk muscle activation during range-of-motion tasks.
AB  - Altered lumbo-pelvic activation sequences have been identified in individuals
      with low back pain. However, an analysis of activation sequences within different
      levels of the trunk musculature has yet to be conducted. This study identified
      the activation sequences characteristic of the trunk musculature during upright
      standing and range-of-motion tasks. Surface electromyography was recorded for
      eight trunk muscles bilaterally during trunk range-of-motion movement tasks in 30
      participants. Cross-correlation was performed on 48 pairings of muscles,
      consisting of one lower- and one mid-level muscle, or one mid-level and one upper
      muscle. Time lags of the maximum cross-correlation coefficient were extracted and
      defined as a top-down or bottom-up activation sequence, or similar activation
      timing. Pairings that demonstrated a specific activation sequence in 50% or more
      of participants were then identified. Similar activation timing was consistently
      identified between muscle pairings for upright standing. Top-down sequences and
      similar timing were identified for abdominal - mid-level pairings in maximum
      flexion and slumped standing, respectively, while both tasks were characterized
      by bottom-up sequences when considering the lumbar and lower-thoracic erector
      spinae. Sequences were more variable across muscle pairings for lateral bend and
      axial twist tasks. These results provide insight into the synergy of the trunk
      musculature for movements in the three planes of motion. These findings can be
      used for comparison to low back pain populations, as altered activation sequences
      in these individuals may contribute to maladaptive loading patterns and
      consequently the development or exacerbation of low back pain. 

PMID- 26209972
TI  - Long-term outcomes of fertility-sparing treatment of atypical polypoid adenomyoma
      with medroxyprogesterone acetate.
AB  - PURPOSE: Our objective was to analyze the long-term oncologic outcomes of
      fertility-preserving hormonal treatment with medroxyprogesterone acetate (MPA) in
      patients with APA. METHODS: In a retrospective chart review, we identified
      patients with APA who were treated with MPA for fertility preservation at our
      hospital between 2001 and 2011. Eighteen patients with histologically diagnosed
      APA were identified. Clinical data including treatment, obstetrical, and
      oncologic outcomes were recorded. RESULTS: The mean observation period was 77.6
      months (median 73.5, range 22-142), and the mean age was 33.6 years. Four
      patients also developed well-differentiated endometrial carcinoma. After the
      treatment, 14 patients (77.8 %) achieved either a complete response or partial
      response. Eight patients experienced recurrence, while four experienced
      persistent disease. Ten patients (55.6 %) eventually underwent hysterectomy. The
      median time to hysterectomy was 40.3 months (range 24-68). Nine patients
      progressed to endometrial cancer, and one experienced persistent APA. Among
      younger patients (<35 years of age), four out of five patients who were married
      could have children. Seven patients (38.9 %) showed no evidence of the disease
      during the observation period (median 60 months, range 22-117 months). No one
      died because of the disease during the observation period. CONCLUSIONS: MPA
      yields a high response rate in APA, and if only younger patients are considered,
      a favorable pregnancy rate can be obtained. However, because recurrence rate is
      high, long-term follow-up under supervision of a trained gynecologic oncologist
      is required. To confirm MPA's utility, multi-center collaboration would be
      warranted.

PMID- 26209973
TI  - Overexpression of the iron transporter NtPIC1 in tobacco mediates tolerance to
      cadmium.
AB  - KEY MESSAGE: Overexpression of the iron transporter NtPIC1 increases iron
      concentration in shoots and reduces Cd uptake/accumulation in plants, mediating
      tolerance to cadmium. Cadmium (Cd) is toxic to plant cells and causes plants to
      display a typical iron (Fe) deficiency phenotype. NtPIC1 (Permease In
      Chloroplast1) is an Fe transporter protein in tobacco, required for Fe
      homeostasis. Based on preliminary results in transformed Saccharomyces cerevisiae
      BY4741 cells, which showed that NtPIC1 expression increased Cd tolerance, this
      study evaluated Cd tolerance in tobacco plants overexpressing NtPIC1 (NtPIC1-OE).
      We show that these plants have longer roots and higher fresh weights than wild
      type (WT) plants after Cd exposure. Under Cd stress, WT plants display more
      chlorosis, stronger growth inhibition, and lower chlorophyll concentrations than
      NtPIC1-OE plants. Importantly, NtPIC1-OE plants had higher Fe concentrations in
      shoots and lower Fe concentrations in roots, and Cd concentrations in NtPIC1-OE
      plants were significantly lower compared to those in WT plants. Moreover, Fe
      transport-related genes (NtPIC1, NtNRAMP1, and NtFER1) were upregulated in NtPIC1
      OE plants, while Fe deficiency-related genes (NtFRO1, NtIRT1, and NtZIP1) that
      mediate Cd uptake were downregulated. We also found that the activities of
      several antioxidative enzymes were significantly higher in NtPIC1-OE plants than
      in WT plants under Cd stress. Overall, our results demonstrate that
      overexpression of NtPIC1 is an efficient way to increase shoot Fe concentrations
      and reduce Cd uptake/accumulation in plants.

PMID- 26209974
TI  - Cotton ACAULIS5 is involved in stem elongation and the plant defense response to
      Verticillium dahliae through thermospermine alteration.
AB  - KEY MESSAGE: Overexpression of GhACL5 , an ACAULIS5 from cotton, in Arabidopsis
      increased plant height and T-Spm level. Silencing of GhACL5 in cotton exhibited a
      dwarf phenotype and reduced resistance to Verticillium dahliae. The Arabidopsis
      thaliana gene ACAULIS5 (ACL5), for which inactivation causes a defect in stem
      elongation, encodes thermospermine (T-Spm) synthase. However, limited information
      is available about improvement in plant height by the overexpression of ACL5
      gene, and the biological functions of ACL5 genes in response to biotic stress.
      Here, this study reports that constitutive expression of the cotton ACL5 gene
      (GhACL5) in Arabidopsis thaliana significantly increased plant height and
      elevated the level of T-Spm. Silencing of that gene in cotton reduced the amount
      of T-Spm and led to a severe dwarf phenotype. Expression of GhACL5 was induced
      upon treatment with the fungal pathogen Verticillium dahliae and plant hormones
      salicylic acid, jasmonic acid, and ethylene in resistant cotton plants, but gene
      silencing in cotton enhanced their susceptibility to V. dahliae infection.
      Furthermore, T-Spm exposure effectively inhibited V. dahliae growth in vitro. In
      summary, GhACL5 expression is related to in planta levels of T-Spm and is
      involved in stem elongation and defense responses against V. dahliae.

PMID- 26209975
TI  - Whither thiotepa (for patients in the USA)?

PMID- 26209976
TI  - Expression Analysis of mir-21 and mir-221 in Cancerous Tissues from Iranian
      Patients with Gastric Cancer.
AB  - BACKGROUND: Early detection is a key to survival for gastric cancer. Molecular
      markers such as miRNA (microRNA) can have great importance in the early diagnosis
      of gastric cancer. Expression of miR-21 and miR-221 are deregulated in many types
      of human cancers. This study aimed to investigate the differences in miRNA
      expression patterns within the Iranian population. METHODS: Total RNA was
      extracted from gastric cancer tissues and adjacent non-cancerous tissues from 32
      patients. Expression levels of miR-21 and miR-221 were detected by Real time RT
      PCR using a specific primer, with 5s rRNA as the internal reference gene.
      RESULTS: Our data showed that the expression levels of miR-21 and miR-221 in
      gastric cancer samples were significantly higher than in paired non-cancerous
      samples (P value less than 0.05). The receiver operating characteristic (ROC)
      analyses yielded the area under the curve (AUC) values of 80.30 for miR-21 and
      93.30 for miR-221, and combined ROC analysis revealed the highest AUC value of
      96.90 in discriminating GC patients from healthy controls. CONCLUSION: It seems
      that miR-21 and miR-221 expression pattern in Iranian patients with gastric
      cancer are similar to any other population. Considering the increased expression
      level of two miRNAs in cancerous tissue compared to normal tissue as well as the
      area under ROC curve, miR-21 and miR-221 can be used for early detection of
      gastric cancer.

PMID- 26209977
TI  - Why is asymptomatic bacteriuria overtreated?: A tertiary care institutional
      survey of resident physicians.
AB  - BACKGROUND: Asymptomatic bacteriuria (ABU) is common and often leads to
      unnecessary antimicrobial use. Reducing antibiotic overuse for ABU is therefore
      an important issue for antimicrobial stewardship. We performed this study to
      investigate the appropriateness of ABU management and to evaluate physicians'
      knowledge and practice regarding ABU. METHODS: We reviewed all urine cultures of
      >=10(5) cfu/mL of bacteria among inpatients in a 900-bed hospital in 2011. Each
      episode of bacteriuria was classified into ABU or urinary tract infection (UTI).
      ABU was defined as a positive urine culture (>=10(5) cfu/mL) without symptoms or
      signs suggesting UTI. In October 2012 a cross-sectional survey of resident
      physicians was undertaken using an anonymous, self-administered questionnaire.
      RESULTS: We identified 219 ABU cases among 1167 positive urine cultures, of which
      70 (32.0 %) were inappropriately treated. Female gender, old age, pyuria,
      hematuria, and positive nitrite on urinalysis were associated with inappropriate
      ABU treatment in a multivariate analysis (P < 0.05). The response rate to the
      survey was 74.2 % (95/128). The mean knowledge score was 37.3 %, and 33.7 % of
      respondents were able to distinguish ABU from UTI, but less than half knew the
      indications for treating ABU. Even after ABU was correctly diagnosed, concerns
      about postoperative infections (38.6 %), UTI (9.1 %), and abnormal urinalysis
      (29.5 %) prevented proper management. About half of the respondents reported to
      prescribing antibiotics for ABU despite knowing they were not indicated.
      CONCLUSIONS: About one third of ABUs were inappropriately managed. Lack of
      knowledge and discrepancies between knowledge and practice, contributed to
      antimicrobial overuse for ABU. Our findings highlight the importance of
      developing interventions, including education, audit and feedback, to tackle the
      problem of inappropriate treatment of ABU.

PMID- 26209978
TI  - Clinical and microbiological features of definite Mycobacterium gordonae
      pulmonary disease: the establishment of diagnostic criteria for low-virulence
      mycobacteria.
AB  - BACKGROUND: Although Mycobacterium gordonae isolation from respiratory samples is
      usually regarded as contamination, M. gordonae can cause definite pulmonary
      disease. The establishment of a standard diagnostic criteria of pulmonary disease
      that is caused by this low virulence mycobacterium is obviously necessary.
      METHODS: We performed clinical research on over 200 cases in which M. gordonae
      was isolated over an 8-year period, focusing on the M. gordonae subtype. Sequence
      analysis of rpoB was performed to identify the genotypes. RESULTS: A total of 287
      respiratory samples (209 cases) were positive for M. gordonae. Twenty-seven cases
      (12.9%) had a positive culture more than twice and 11 of these cases (5.3%) had
      more than three positive cultures. Ultimately, three cases (1.4%) were newly
      diagnosed as M. gordonae pulmonary disease using our own diagnostic criteria. In
      all of the identified M. gordonae cases, the cultures tested positive with a
      Mycobacteria Growth Indicator Tube test at 24 days; however, in patients with
      definitive pulmonary disease, the cultures were positive at 9 days. A subtype
      analysis revealed that all of the definitive disease cases had subtype C.
      CONCLUSION: The time taken to detect a positive culture and subtype of the
      isolates could be used as the diagnostic criteria for definite M. gordonae
      pulmonary disease.

PMID- 26209980
TI  - Accuracy of rapid disposition by emergency clinicians.
AB  - Objectives Rapid disposition protocols are increasingly being considered for
      implementation in emergency departments (EDs). Among patients presenting to an
      adult tertiary referral hospital, this study aimed to compare prediction accuracy
      of a rapid disposition decision at the conclusion of history and examination,
      compared with disposition following standard assessment. Methods Prospective
      observational data were collected for 1 month between October and November 2012.
      Emergency clinicians (including physicians, registrars, hospital medical
      officers, interns and nurse practitioners) filled out a questionnaire within 5min
      of obtaining a history and clinical examination for eligible patients. Predicted
      patient disposition (representing 'rapid disposition') was compared with final
      disposition (determined by 'standard assessment'). Results There were 301 patient
      episodes included in the study. Predicted disposition was correct in 249 (82.7%,
      95% confidence interval (CI) 78.0-86.8) cases. Accuracy of predicting discharge
      to home appeared highest among emergency physicians at 95.8% (95% CI 78.9-99.9).
      Overall accuracy at predicting admission was 79.7% (95% CI 67.2-89.0). The
      remaining 20.3% (95% CI 11.0-32.8) were not admitted following standard
      assessment. Conclusion Rapid disposition by ED clinicians can predict patient
      destination accurately but was associated with a potential increase in admission
      rates. Any model of care using rapid disposition decision making should involve
      establishment of inpatient systems for further assessment, and a culture of
      timely inpatient team transfer of patients to the most appropriate treating team
      for ongoing patient management. What is known about the topic? In response to the
      National Emergency Access Targets, there has been widespread adoption of rapid
      disposition-themed care models across Australia. Although there is emerging data
      that clinicians can predict disposition accurately, this data is currently
      limited. What does this paper add? Results of this study support the previously
      limited evidence that ED practitioners can accurately predict disposition early
      in the patient journey through ED, and that accuracy is similar across clinician
      groups. In addition to overall prediction accuracy, admission, discharge and
      treating team predictions were separately measured. These additional outcomes
      lend insight into safety and performance aspects relating to a rapid disposition
      model of care. What are the implications for practitioners? This study offers
      practical insights that could aid safe and efficient implementation of a rapid
      disposition model of care.

PMID- 26209981
TI  - Management of childhood asthma in general practice.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) are recommended for children with
      moderate or severe persistent asthma. The aims of this paper were to determine
      changes in childhood asthma management rates between 2004-14, and to examine
      current medication use and level of control in children attending general
      practice. METHODS: National BEACH data were used to investigate childhood (<15
      years) asthma management rate. Prevalence, medication use and asthma control
      (Global Initiative for Asthma guidelines) were recorded for a subset of children.
      RESULTS: The management rate did not change over time. Prevalence was 13.7%. ICS
      were taken by 42.8% of children. Asthma was well controlled for 51.8%, partly
      controlled for 30.4% and uncontrolled for 17.9% of children. This study
      highlights the need to monitor appropriate medication use, particularly ICS/long
      acting beta-agonist use, for asthma control in children.

PMID- 26209979
TI  - Complex regulation of Hsf1-Skn7 activities by the catalytic subunits of PKA in
      Saccharomyces cerevisiae: experimental and computational evidences.
AB  - BACKGROUND: The cAMP-dependent protein kinase regulatory network (PKA-RN)
      regulates metabolism, memory, learning, development, and response to stress.
      Previous models of this network considered the catalytic subunits (CS) as a
      single entity, overlooking their functional individualities. Furthermore, PKA-RN
      dynamics are often measured through cAMP levels in nutrient-depleted cells
      shortly after being fed with glucose, dismissing downstream physiological
      processes. RESULTS: Here we show that temperature stress, along with deletion of
      PKA-RN genes, significantly affected HSE-dependent gene expression and the
      dynamics of the PKA-RN in cells growing in exponential phase. Our genetic
      analysis revealed complex regulatory interactions between the CS that influenced
      the inhibition of Hsf1/Skn7 transcription factors. Accordingly, we found new
      roles in growth control and stress response for Hsf1/Skn7 when PKA activity was
      low (cdc25Delta cells). Experimental results were used to propose an interaction
      scheme for the PKA-RN and to build an extension of a classic synchronous discrete
      modeling framework. Our computational model reproduced the experimental data and
      predicted complex interactions between the CS and the existence of a repressor of
      Hsf1/Skn7 that is activated by the CS. Additional genetic analysis identified
      Ssa1 and Ssa2 chaperones as such repressors. Further modeling of the new data
      foresaw a third repressor of Hsf1/Skn7, active only in the absence of Tpk2. By
      averaging the network state over all its attractors, a good quantitative
      agreement between computational and experimental results was obtained, as the
      averages reflected more accurately the population measurements. CONCLUSIONS: The
      assumption of PKA being one molecular entity has hindered the study of a wide
      range of behaviors. Additionally, the dynamics of HSE-dependent gene expression
      cannot be simulated accurately by considering the activity of single PKA-RN
      components (i.e., cAMP, individual CS, Bcy1, etc.). We show that the differential
      roles of the CS are essential to understand the dynamics of the PKA-RN and its
      targets. Our systems level approach, which combined experimental results with
      theoretical modeling, unveils the relevance of the interaction scheme for the CS
      and offers quantitative predictions for several scenarios (WT vs. mutants in PKA
      RN genes and growth at optimal temperature vs. heat shock).

PMID- 26209982
TI  - Sleep apnoea in the child.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) is a condition causing repetitive
      episodes of upper airway obstruction during sleep, leading to hypoxia and/or
      sleep disturbance. OSA affects 1-5% of children and has important implications
      for learning, behaviour and cardiovascular health. OBJECTIVE: The aim of this
      article is to provide a suggested approach to case finding and treatment of OSA
      for general practitioners. DISCUSSION: Snoring or noisy breathing during sleep is
      the cardinal symptom of OSA, and should be specifically sought in children with
      disturbed sleep, nasal obstruction and large tonsils. Multi-channel physiological
      recording in a paediatric sleep laboratory is available to formally define the
      condition. Treatment with adenotonsillectomy usually leads to improvements in key
      domains. Milder disease may respond to intranasal steroids or anti-inflammatory
      agents.

PMID- 26209983
TI  - Managing childhood migraine.
AB  - BACKGROUND: Childhood migraines create a significant health burden and are
      probably under-diagnosed and treated. OBJECTIVES: The aim of this article is to
      offer a systematic approach to the management of migraine. DISCUSSION: A
      systematic approach to the presentation of migraines in children can help to
      alleviate parental and physician anxiety and allow for an accurate diagnosis.
      Treatment is multifactorial but pharmacological intervention should certainly
      play a role along with adjustment of environmental factors and addressing
      possible underlying psychosocial factors. Referral to a general practitioner (GP)
      with specialist interests, paediatrician, adolescent physician or neurologist may
      be appropriate. In extreme circumstances, referral to the emergency department is
      a reasonable option to allow aggressive abortive treatments, but ongoing
      management should be coordinated through the GP.

PMID- 26209984
TI  - The wheezing child: an algorithm.
AB  - BACKGROUND: Wheezing is a common presentation in young children. Diagnosis and
      treatment of these children can be challenging, as arriving at a final diagnosis
      often requires a process of elimination. OBJECTIVE: This article aims to provide
      an algorithm for managing a young child with wheeze in the primary care setting.
      We will aim to address key questions of some controversy that relate to this
      algorithm: 1. Does the child actually have wheeze - how accurate is the parents'
      description? 2. Do antibiotics have a role? The emergence of protracted bacterial
      bronchitis (PBB) 3. Is it asthma or viral wheeze, and which children outgrow this
      phenomenon? DISCUSSION: The exact cause of wheezing can be unclear in children,
      particularly those under pre-school age (<6 years). An algorithmic approach based
      on history and response to treatment often helps to distinguish between the
      differential diagnoses. We present one such algorithmic approach and introduce
      the diagnosis of persistent bacterial bronchitis in line with current thinking
      from the past 10 years.

PMID- 26209985
TI  - The use of fenofibrate in the management of patients with diabetic retinopathy:
      an evidence-based review.
AB  - BACKGROUND: Diabetic retinopathy is a significant cause of vision impairment,
      especially affecting those of working age. There are two large, randomised
      controlled trials examining the effect of fenofibrate on diabetic retinopathy.
      OBJECTIVE: We summarise their findings, and report on the available safety data.
      DISCUSSION: The FIELD study reported that patients treated with fenofibrate had a
      statistically significant relative risk reduction in the need for laser treatment
      for maculopathy and proliferative retinopathy. The ACCORD-Eye study reported a
      statistically significant reduction in diabetic retinopathy progression in
      patients treated with fenofibrate and statin combination therapy compared to
      statin therapy alone. There is firm evidence that fenofibrate slows the
      progression of diabetic retinopathy and the need for more invasive treatment
      modalities in patients with type 2 diabetes, especially those with pre-existing
      retinopathy. In October 2013, Australia became the first country in the world to
      approve the use of this medication for this specific indication.

PMID- 26209986
TI  - Your questions about complementary medicines answered.
AB  - This is the first article in a series providing evidence-based answers to common
      ?questions about complementary medicines from consumers and healthcare
      professionals. 

PMID- 26209987
TI  - Your questions about complementary medicines answered: glucosamine.
AB  - This is the second article in a series providing evidence-based answers to common
      questions about complementary medicines from consumers and healthcare
      professionals. 

PMID- 26209988
TI  - Acute onset of widespread pustular eruption.

PMID- 26209989
TI  - A handyman with hand ulcers.

PMID- 26209990
TI  - Improving cultural respect to improve Aboriginal health in general practice: a
      multi-methods and multi-perspective pragmatic study.
AB  - BACKGROUND: To address the gap in access to healthcare between Aboriginal people
      and other Australians, we developed Ways of Thinking, Ways of Doing (WoTWoD) to
      embed cultural respect into routine clinical practice. WoTWoD includes a
      workshop, toolkit and cultural mentors in a partnership of general practice and
      Aboriginal organisations. The aim of this study was to examine the im-pact of
      WoTWoD on cultural respect, health checks and risk factor management for
      Aboriginal patients in general practice. METHODS: A multi-methods and multi
      perspective pre- and-post-intervention pragmatic study with 10 general practices
      was undertaken, using information from medical records, practice staff, cultural
      mentors and patients. RESULTS: Cultural respect, service and clinical measures
      improved after implementing WoTWoD. Qualitative information confirmed and
      explained improvements. Knowledge of Aboriginal history needed further
      improvement. DISCUSSION: The WoTWoD may improve culturally appropriate care in
      general practice. Further research requires adequately powered randomised
      controlled trials.

PMID- 26209991
TI  - Clinical exposure of interns during a general practice placement.
AB  - BACKGROUND: For more than a decade, junior doctors have undertaken general
      practice rotations; however, little is known about the breadth of medical
      conditions seen. This study aims to determine the breadth of clinical
      presentations encountered by interns during a rotation. METHODS: Data were
      collected on all patients seen by interns at an RA-2 general practice during 2012
      13. Each condition identified was compared with the Australian Curriculum
      Framework for Junior Doctors (ACFJD) and coded according to the International
      Classification of Diseases 10th revision (ICD-10). RESULTS: Interns saw an
      average of 482.2 (SD = 38) patients per rotation (10.7 patients per day), 150.3
      (SD = 15.4) ICD-10 codes per rotation and 49.8 (SD = 4.9; 57.2%) of the listed
      clinical symptoms and conditions in the ACFJD.

PMID- 26209992
TI  - Exploring female GPs' perceptions about medical leadership.
AB  - BACKGROUND: Women are increasingly entering the Australian general practice
      workforce. This study aims to explore female general practitioners' (GPs')
      perceptions of possible barriers to leadership and professional roles in the
      workforce. METHODS: A purposive, convenience sample of 30 female GPs in active
      practice was approached in February, 2012. An anonymous, pa-per-based, semi
      quantitative survey sought to identify participation and leadership confidence
      within general practice in a number of professional roles. RESULTS: The top two
      barriers participants identified for after-hours medical meetings were energy to
      attend and geographical location. For after-hours care, the top two barriers
      identified were energy and self-motivation. Few participants aspired to
      'leadership' activities. 'Medical mentoring' was most likely to attract them into
      leadership. DISCUSSION: It is important female GPs' perspectives are explored in
      general practice. This small survey suggests further studies are needed in the
      importance of energy limitations and lack of self-confidence in restricting
      female GPs' capacity to fully engage in professional roles.

PMID- 26209993
TI  - Current rehabilitation processes do not prevent long-term impairments after
      treatment for breast cancer in Australia.
AB  - BACKGROUND: Our aims were to determine if and how advice regarding physical
      rehabilitation (arm-specific and general exercise) was provided after treatment
      for breast cancer, as well as the prevalence of physical impairments following
      treatment for breast cancer in an Australian population. METHODS: Members of the
      Review and Survey Group of the Breast Cancer Network Australia participated in a
      validated web-based survey. RESULTS: Participants included 186 women who
      underwent axillary node dissection and 201 who underwent sentinel node biopsy for
      breast cancer. Of the respondents, 75% reported receiving arm-specific exercise
      advice following surgery and 44% were advised on the importance of general
      exercise at some point during treatment. Despite this, upper limb impairments
      were commonly reported during treatment and 1 year after surgery, particularly
      for women who had undergone axillary node dissection. DISCUSSION: Although
      rehabilitation advice is commonly offered to women treated for breast cancer in
      Australia, pain and reduced arm function remain common in women more than 1 year
      after surgery.

PMID- 26209994
TI  - BEACH program update.
AB  - BACKGROUND: The Bettering the Evaluation and Care of Health (BEACH) program, a
      continuous national study of general practice clinical activity, is now in its
      18th year. In March 2015 the database included details of almost 1.7 million
      encounters from 16,639 participants, representing about 10,300 individual general
      practitioners (GPs). OBJECTIVES: This paper summarises the BEACH methods, the
      uses to which the data supplied by participating GPs are put and the many
      publications resulting from the program, with an indication of how these can be
      accessed by readers. DISCUSSION: BEACH is the only continuous nationally
      representative study of general practice in the world that provides direct
      linkage of GP management actions to the problem being managed. This paper
      provides the reference point for the coming series of more specific articles
      associated with the theme of each edition of Australian Family Physician.

PMID- 26209995
TI  - E-cigarettes and the law in Australia.
AB  - BACKGROUND: Australian laws covering electronic cigarettes (e-cigarettes) are
      complex and vary between jurisdictions. The supply of nicotine-containing e
      cigarettes in Australia is illegal. Possession or use of nicotine in e-cigarettes
      without approval is also illegal and the sale of non-nicotine e-cigarettes is
      illegal in some states. Despite the current legal barriers, the use of e
      cigarettes by Australian smokers has increased over recent years. OBJECTIVE: This
      article summarises these laws, recent cases involving e-cigarettes and what is
      known about their safety and efficacy as cessation aids. DISCUSSION: Australian
      medical practitioners are likely to be asked about e-cigarettes by patients who
      smoke and may be interested in using them to quit smoking. The efficacy of e
      cigarettes as a cessation aid has not been fully established. The health risk of
      long-term use is also unknown, although it is probably less than that of smoking
      cigarettes. There is an urgent need for research on the health effects of e
      cigarettes and their use in quitting smoking.

PMID- 26209996
TI  - Research ethics and approval process: A guide for new GP researchers.
AB  - BACKGROUND: The underlying moral principles and values, and the virtues held as
      desirable for a researcher, should be reflected upon and embedded in the
      research. The foundation step is to download the National Health and Medical
      Research Council's (NHMRC's) National Statement on Ethical Conduct in Human
      Research and the NHMRC's Guidelines for Ethical Conduct in Aboriginal and Torres
      Strait Islander Health Research to use as references. OBJECTIVE: This paper draws
      on the experience of The Royal Australian College of General Practitioners'
      (RACGP's) National Research and Evaluation Ethics Committee to provide an eight
      step approach to the research ethics process. DISCUSSION: The researcher should
      use the research ethics process as an opportunity to foster and guide the
      development and conduct of ethical research.

PMID- 26209997
TI  - Shaping our own destiny by ?Choosing Wisely.

PMID- 26209998
TI  - Let's listen to patients' and GPs' perspectives on alcohol-screening research.
AB  - Alcohol-screening questionnaires have been found to be effective in the early
      detection of risky drinking but are rarely used by clinicians in primary care. As
      research agenda tend not to seek the perspectives of patients and general
      practitioners (GPs), the best way to address the barriers to implementation is
      unclear. Contemporary research to explore patient beliefs and attitudes towards
      alcohol enquiry by GPs is needed. 

PMID- 26209999
TI  - Benefits of less frequent injections in advanced prostate cancer.
AB  - Leuprorelin is indicated for the palliative treatment of advanced prostate cancer
      (APC) and is available as 1, 3, 4 and 6-monthly injections. There are advantages
      of longer leuprorelin injection intervals in the treatment of APC. Across all
      injection intervals, efficacy is similar and the majority of patients achieve
      testosterone suppression and normalisation of prostate-specific antigent.
      Treatment is well tolerated. Six-monthly leuprorelin injections are less costly
      to the healthcare system than the shorter interval injections. 

PMID- 26210000
TI  - Prevalence and Risk Factors for Low Habitual Walking Speed in Nursing Home
      Residents: An Observational Study.
AB  - OBJECTIVE: To quantify habitual walking speed and estimate the prevalence of low
      habitual walking speed (<0.8m/s and <0.5m/s) in nursing home residents; and
      secondarily to gain some insight into whether demographic, health, and functional
      outcomes could predict the nursing home residents' walking speed. DESIGN: Cross
      sectional study. SETTING: Eleven nursing homes. PARTICIPANTS: Nursing home
      residents (N=102 [37%] of 273 eligible, randomly selected residents from 11
      nursing homes consented to participate in this study). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The primary outcome was habitual walking speed
      assessed over a distance of 2.4m. Secondary outcomes including body composition,
      muscle strength, balance and physical performance as assessed via the Short
      Physical Performance Battery, and historical and current demographic and health
      measures were all assessed as potential predictors of walking speed. RESULTS:
      Mean walking speed was .37+/-.26 m/s, meaning that 97% and 75% of participants
      had walking speeds <0.8m/s and <0.5m/s, respectively. Multivariable linear
      regression identified physical activity status before 50 years of age and daily
      sitting time as independent predictors of walking speed (r(2)=.25, P<.05),
      although this regression only accounted for 25% of the variance in walking speed.
      CONCLUSIONS: Almost all participants in this study had below-normal walking
      speed, a known clinical predictor of physical performance. Because walking speed
      is a clinical marker of many age-related adverse outcomes in older age, efforts
      to increase or at least maintain walking speed in nursing home residents should
      be considered. Some evidence suggests that progressive resistance training may
      offset these declines in walking speed.

PMID- 26210001
TI  - An efficient conditional random field approach for automatic and interactive
      neuron segmentation.
AB  - We present a new graphical-model-based method for automatic and interactive
      segmentation of neuron structures from electron microscopy (EM) images. For
      automated reconstruction, our learning based model selects a collection of nodes
      from a hierarchical merging tree as the proposed segmentation. More specifically,
      this is achieved by training a conditional random field (CRF) whose underlying
      graph is the watershed merging tree. The maximum a posteriori (MAP) prediction of
      the CRF is the output segmentation. Our results are comparable to the results of
      state-of-the-art methods. Furthermore, both the inference and the training are
      very efficient as the graph is tree-structured. The problem of neuron
      segmentation requires extremely high segmentation quality. Therefore,
      proofreading, namely, interactively correcting mistakes of the automatic method,
      is a necessary module in the pipeline. Based on our efficient tree-structured
      inference algorithm, we develop an interactive segmentation framework which only
      selects locations where the model is uncertain for a user to proofread. The
      uncertainty is measured by the marginals of the graphical model. Only giving a
      limited number of choices makes the user interaction very efficient. Based on
      user corrections, our framework modifies the merging tree and thus improves the
      segmentation globally. 

PMID- 26210002
TI  - Editorial Comment.

PMID- 26210003
TI  - Reply: To PMID 26210002.

PMID- 26210004
TI  - The Co-occurring Syndrome-Coexisting Erectile Dysfunction and Benign Prostatic
      Hyperplasia and Their Clinical Correlates in Aging Men: Results From the National
      Health and Nutrition Examination Survey.
AB  - OBJECTIVE: To establish a descriptive profile of men with coexistent erectile
      dysfunction (ED) and/or benign prostatic hyperplasia (BPH), ED only or BPH only
      compared to those with neither condition and to identify the determinants of
      coexisting disease. MATERIALS AND METHODS: Self-report and/or medication use
      measures defining ED and BPH were assessed in men aged >=40 years (N = 2142)
      between 2001 and 2004 using the National Health and Nutrition Examination
      Surveys. Descriptive analyses examined the ED and/or BPH covariate distribution.
      Logistic regressions calculated odds ratios (ORs, 95% confidence interval)
      comparing men with ED and/or BPH, BPH only, or ED only to men with neither
      condition. RESULTS: Of 393 men with BPH, 57.8% had coexistent ED, confirming the
      moderately strong co-occurrence of the conditions (P <.0001). Coexisting ED
      and/or BPH occurred in 10.6% of participants, whereas 24.4% and 7.7% reported ED
      and BPH. After age 60, the odds of reporting ED, BPH, or ED/BPH vs neither almost
      tripled per decade of increasing age, corresponding to prevalence increases. The
      unadjusted odds of ED and/or BPH vs no disease increased 1.3 times per prostate
      specific antigen unit (ng/mL) increase and 1.1 times per C-reactive protein unit
      (mg/dL) increase. Other predisposing factors for ED and/or BPH included higher
      body mass index (OR = 2.5), increased antidiabetic (OR = 2.9) or proton pump
      inhibitor use (OR = 2.3), increased healthcare visits (>=4; OR = 3.5), and more
      frequent urinary voiding difficulties (OR = 9.7). CONCLUSION: Co-occurring ED
      and/or BPH is evident in ~10% of men >=40 years old and is associated with
      significant clinical correlates. Clinicians need to pay greater attention to this
      clinically important syndrome in aging men.

PMID- 26210005
TI  - Management Protocol for Chylous Ascites After Laparoscopic Nephrectomy.
AB  - OBJECTIVE: To devise a management protocol for chylous ascites after laparoscopic
      nephrectomy. PATIENTS AND METHODS: We retrospectively reviewed the data of the
      patients that underwent laparoscopic nephrectomy between January 2010 and January
      2014 in our institution for different indications and were diagnosed with chylous
      ascites. We also analyzed a different management protocol that was used. RESULTS:
      The overall incident rate of chylous ascites was 0.77%. It was more commonly seen
      on left side and with simple nephrectomy rather than radical. Three out of 9
      patients were managed by surgical intervention, rest were successfully managed on
      conservative treatment in the form of dietary modification, total parenteral
      nutrition, or octreotide. CONCLUSION: Chylous ascites is a rare but morbid
      condition following laparoscopic nephrectomy. To manage this complication, we
      propose preventive and treatment strategies based on symptoms and amount of
      chylous ascites using our experience and review of the literature.

PMID- 26210006
TI  - Geographic Variation in the Quality of Secondary Prevention for Nephrolithiasis.
AB  - OBJECTIVE: To examine the variation in the quality of secondary prevention for
      nephrolithiasis across health care markets. METHODS: Using analytical files from
      Litholink Corporation (2003-2012), we identified adults with nephrolithiasis and
      abnormal urine biochemistries on 24-hour urine collection. After assigning all
      patients to a hospital referral region (HRR), we determined the proportion of
      patients in each HRR who underwent on-treatment follow-up testing (our measure of
      quality). We then fitted multivariate hierarchical regression models to quantify
      the amount of variation in this proportion across HRRs. Finally, we examined for
      associations between a patient's odds of on-treatment follow-up testing and the
      supply of primary care and specialist physicians in an HRR. RESULTS: The mean
      rate on-treatment follow-up testing was exceedingly low at only 11.9%. This rate
      has been stable over time. There was fourfold variation in this rate across HRRs
      from as little as 6.6% to as high as 23.4%. Those HRRs with higher on-treatment
      follow-up testing rates tended to have a wealthier and more educated population
      (P = .01). Receipt of on-treatment follow-up testing was not associated with the
      number of specialists per capita. CONCLUSION: Wide geographic variation exists in
      the quality of secondary prevention for patients with nephrolithiasis. Given that
      current guidelines recommend on-treatment follow-up testing, efforts to increase
      its uptake are needed.

PMID- 26210007
TI  - Canalization of freeze tolerance in an alpine grasshopper.
AB  - In the Rock and Pillar Range, New Zealand, the alpine grasshopper, Sigaus
      australis Hutton, survives equilibrium freezing (EF) all-year round. A comparison
      of freeze tolerance (FT) in grasshoppers over four austral seasons for a 1 year
      period finds that: (a) the majority (>70%) of the sample population of
      grasshoppers survive single freeze-stress throughout the year; (b) exposure to
      increased freeze stress (multiple freeze-stress events) does not lead to a loss
      of freeze tolerance; and (c) responses to increased freeze stress reveal seasonal
      tuning of the FT adaptation to environmental temperatures. The Rock and Pillar
      sample population provides a clear example of the canalization of the FT
      adaptation. Seasonal variability in the extent of tolerance of multiple freezing
      events indicates that physiology is modulated to environmental temperatures by
      phenotypic plasticity - i.e. the FT adaptation is permanent and adjustable.

PMID- 26210008
TI  - Validation of microSecure vitrification (MUS-VTF) for the effective
      cryopreservation of human embryos and oocytes.
AB  - A novel, aseptic closed system vitrification (VTF) technique for the
      cryopreservation of embryos and oocytes has been developed and clinically
      validated in this study. It combines the practicality of embryo-containing
      sterile flexipettes stored safely and securely with 0.3 ml CBSTM embryo straws
      possessing weld seals. The cooling and warming rates of this double container
      system were determined using a data logger. Upon direct plunging into LN(2), the
      flexipettes cool at an average rate of 1391 degrees C/min, while warming occurs
      at an average rate of 6233 degrees C/min in a 37 degrees C 0.5 M sucrose bath.
      Direct deposition of the flexipette into a warming bath insured a rapid
      transition between -100 and -60 degrees C to minimize potentially harmful
      recrystalization associated with devitrification. In conclusion, the MUS-VTF
      system has exhibited higher (p<0.05) intact survival, implantation and live birth
      rates than conventional slow freezing methods. The effective embryo transfer of
      vitrified blastocysts proved similar to or better than fresh embryo transfer
      outcomes. The sustained clinical use of MUS-VTF has justified a change in our
      infertility practice. Capsule: The microSecure vitrification (MUS-VTF) procedure
      is a low-cost, non-commercial, aseptic, closed system that offers technical
      simplicity and repeatability, while effectively attaining an estimated 4:1
      warming-to-cooling rate ratio, which supports excellent embryo survival and
      sustained viability.

PMID- 26210009
TI  - Transition to injecting drug use in Iran: A systematic review of qualitative and
      quantitative evidence.
AB  - BACKGROUND: Injection drug use, a behavior associated with significant adverse
      health effects, has been increasing over the past decade in Iran. This study aims
      to systematically review the epidemiological and qualitative evidence on factors
      that facilitate or protect the transition to injection drug use in Iran. METHODS:
      We conducted electronic searches in five international (Medline, Web of Science,
      EMBASE, CINAHL, PsycINFO), one regional (IMEMR) and three Iranian (Iranmedex,
      Iranpsych, IranDoc) databases, as well as contacting experts in the field. Two
      trained researchers screened documents to identify relevant studies and
      independently dual-extracted data following pre-specified protocol. We applied
      principles of thematic analysis for qualitative data and applied a random effect
      meta-analysis model for age of first injection. RESULTS: A total of 38 documents
      from 31 studies met eligibility criteria, from which more than 50% were
      implemented from 2006 to 2008. The weighted mean age of first injection was 25.8
      (95% Confidence Interval: 25.3-26.2). Between 1998 and 2011, the age of first
      injection was relatively stable. Overall, drug users had used drugs for 6-7 years
      before they started injection use. Heroin was the first drug of injection in the
      majority of the cases. We identified factors influencing the initiation of or
      transition to injection use at various levels, including: (1) individual
      (pleasure-seeking behavior, curiosity and development of drug dependency commonly
      reported), (2) social and environmental (role of peer drug users in the first
      injection use, the economic efficiency associated with injections and the wide
      availability of injectable form of drugs in the market). CONCLUSION: Harm
      reduction policies in Iran have almost exclusively focused on drug injectors in
      Iran. However, given the extent of the non-injection drug use epidemic, evidence
      from this study can provide insight on points of interventions for the prevention
      of the transition to injection use.

PMID- 26210010
TI  - Influence of the nanoprecipitation conditions on the supramolecular structure of
      squalenoyled nanoparticles.
AB  - Hydrophobic organic compounds dissolved in a polar solvent can self-assemble into
      nanoparticles (NPs) upon nanoprecipitation into water. In the present study, we
      have investigated the structure of squalenacetyl-adenosine (SQAc-Ad)
      nanoparticles which were previously found to exhibit impressive neuroprotective
      activity. When obtained by nanoprecipitation of a SQAc-Ad ethanolic solution into
      water, two different supramolecular organizations of SQAc-Ad NPs were evidenced,
      depending on the water-to-ethanol volume ratio. It has been shown that a fraction
      of the solvent remained associated with the NPs, despite prolonged evaporation
      under reduced pressure after nanoprecipitation, and that this residual solvent
      dramatically affected their structure. This study points to the importance of
      being in the "Ouzo" region to minimize the amount and effect of residual solvent
      and to control the structure of NPs. 

PMID- 26210011
TI  - Are We Examining Our Patients Properly and Can We Do a Better Job?

PMID- 26210012
TI  - Association of the presence of influenza A virus and porcine reproductive and
      respiratory syndrome virus in sow farms with post-weaning mortality.
AB  - Influenza A virus (IAV) and porcine reproductive and respiratory syndrome virus
      (PRRSV) are among the most important pathogens affecting pigs worldwide. Their
      effect on post-weaning mortality can be substantial and may be potentiated by
      other concomitant factors. Here, the objective was to evaluate the association
      between IAV and PRRSV infection at weaning with post-weaning mortality observed
      in wean-to-finish farms in order to better quantify the full impact of their
      presence in breeding herds. IAV and PRRSV presence was assessed by real time
      reverse transcription (RRT)-PCR on oral fluid samples from suckling piglets in
      nine sow farms. Production data from 177 batches of growing pigs weaned one week
      before/after IAV and PRRSV testing were analyzed to measure the association
      between IAV and/or PRRSV test results and mortality recorded for a given batch
      through the use of Bayesian mixed effects negative binomial multivariable
      regression model. The model accounted for potential confounders such as flow,
      date at weaning, days on feed and batch size. A statistically important
      association between IAV (incidence ratio (IR)=1.18, 95% posterior probability
      interval 1.15-1.21) and PRRSV (IR=1.41, 95% PPI 1.30-1.52) with post-weaning
      mortality was detected, with season and number of days on feed also associated.
      Our results suggest that infection with IAV or PRRSV in the pre-weaning period is
      associated with an increase in post-weaning mortality. This association should be
      taken into consideration when measuring the impact of IAV and PRRSV in breeding
      herds. 

PMID- 26210013
TI  - Tautomeric conversion, vibrational spectra, and density functional studies on
      peripheral sulfur derivatives of benzothiazole and benzothiazoline isomers.
AB  - The room temperature structural (tautomerism, dimerization, conformational
      preference, geometry parameters) and vibrational spectral (IR and Raman) analyses
      have been performed on benzothiazoline (benzothiazoline-2-thione, 3-methyl
      benzothiazoline-2-thione) and benzothiazole [2-mercaptobenzothiazole, 2
      methylthiobenzothiazole, and bis(benzothiazole-2-ylthio)ethane] derivatives at
      the B3LYP/6-311++G(**) level of theory. Although the keto to enol transition
      barriers are too high over the most stable benzothiazoline isomers, vibrational
      spectral analyses reveal some major bands of benzothiazole isomers in the present
      room temperature experimental FT-IR and FT-Raman specta. Therefore, benzothiazole
      isomers exist at rare amounts in the powdered samples that are mainly composed of
      benzothiazoline isomers. The benzothiazole isomers have two stable conformations
      due to the orientation of their SH and SCH3 moieties. The energetic and
      vibrational spectral analyses suggest that the benzothiazoline-2-thione molecules
      can be stabilized further through the NH?S intermolecular hydrogen bonds in solid
      phase. All observed fundamental vibrational bands of the molecules have been
      assigned based on the calculated mode frequencies and IR/Raman intensities. The
      mode assignments have been expressed in terms of internal coordinates and their
      percent potential energy distributions. The effects of substitution at the
      nitrogen and peripheral sulfur atoms have been analyzed for the geometries and
      vibrational bands of the molecules.

PMID- 26210014
TI  - Spectroscopic investigations on the interactions of AgTiO2 nanoparticles with
      lysozyme and its influence on the binding of lysozyme with drug molecule.
AB  - Binding of lysozyme with AgTiO2 nanoparticles was analyzed by using absorption,
      fluorescence, time resolved and synchronous fluorescence measurements. In the
      presence of AgTiO2 nanoparticles, the fluorescence intensity of lysozyme was
      decreased. Static type of binding was confirmed through lifetime and ground state
      absorption measurements. From the fluorescence quenching data, the binding
      constant and the number of binding sites were found to be 1.5*10(4)M(-1) and
      1.03, respectively. From the synchronous fluorescence spectroscopic measurements,
      tryptophan residue in lysozyme was found to have interaction with the
      nanoparticles. Further, the influence of AgTiO2 nanoparticles on the binding
      strength of lysozyme with a drug molecule was analyzed through fluorescence
      quenching methods. The presence of nanoparticles decreases the binding capability
      of drug with protein. Overall, the observed results will provide basic insights
      on the utilization of nanoparticles in drug delivery applications.

PMID- 26210015
TI  - Effect of annealing on the structural, optical and emissive properties of
      SrWO4:Ln(3+) (Dy(3+), Eu(3+) and Sm(3+)) nanoparticles.
AB  - Lanthanide ions, Ln(3+) (Dy(3+), Eu(3+) and Sm(3+)) doped SrWO4 nanoparticles
      were synthesized using ethylene glycol (EG) as a capping agent as well as
      reaction medium. The X-ray diffraction (XRD) study reveals that all the Ln(3+)
      (Dy(3+), Eu(3+) and Sm(3+)) doped samples are well crystalline in nature with a
      tetragonal scheelite structure of SrWO4 phase. TG study reveals that the
      nanophosphors are thermally stable. Fourier transform infrared spectroscopy
      (FTIR) and Raman spectroscopy techniques were used to obtain the information
      about internal and external vibrational modes present in the SrWO4 structure.
      Optical properties were investigated using UV-vis and photoluminescence (PL)
      spectroscopy. The average crystallite size was calculated using Debye-Scherrer's
      for as-prepared and 800 degrees C annealed samples and is found to be in the
      range of ~35-70nm. The luminescence intensity of Eu(3+) doped SrWO4 nanoparticles
      under 364nm excitation wavelength reveals that (5)D0->(7)F2 transition at ~613nm
      (red) is more prominent than that of (5)D0->(7)F1 transition at ~590nm (orange).
      Also upon excitation by UV radiation, the SrWO4:Dy(3+) phosphor shows the yellow
      and blue transition lines appearing at ~572 and 484nm which are the
      characteristic electronic transitions of (4)F9/2-(6)H13/2 and (4)F9/2-(6)H15/2
      emission line of Dy(3+), respectively. Also Sm(3+) doped SrWO4 nanophosphor shows
      its characteristic emission lines in the range of 550-720nm, corresponding to
      (4)G5/2->(6)HJ (J=5/2, 7/2, 9/2 and 11/2) transitions of Sm(3+) ions. The
      predominant orange red color can be attributed to (4)G5/2->(6)H9/2 located at
      ~642nm. This is related to the polarizing effect due to the energy transfer from
      WO4(2-) to the Eu(3+), Dy(3+) and Sm(3+) sites, respectively. Effect of annealing
      on the photoluminescence properties of samples has been studied and it was found
      that luminescence intensity increases up to ~3 times on heating the samples at
      800 degrees C. This may be due to reduction in non-radiative decay channels
      pathways and reduced surface defects associated with the samples. These studies
      show that these Ln(3+) (Dy(3+), Eu(3+) and Sm(3+)) doped SrWO4 nanophosphors may
      be used as potential candidates for the advancement in LEDs.

PMID- 26210016
TI  - Mixed ligand complexes of Cu(II)/Zn(II) ions containing (m-)/(p-) carboxylato
      phenyl azo pentane 2,4-dione and 2,2'-bipyridine/1,10 phenanthroline: Synthesis,
      characterization, DNA binding, nuclease and topoisomerase I inhibitory activity.
AB  - Metal complexes of type [Cu(L1H)2(bpy)] (1), [Zn(L1H)2(bpy)] (2), [Cu(L2H)2(bpy)]
      (3) and [Cu(L2H)2(Phen)] (4) (L1H2=3-[N'-(1-acetyl-2-oxo-propylidene)-hydrazino]
      benzoic acid, L2H2=4-[N'-(1-acetyl-2-oxo-propylidene)-hydrazino]-benzoic acid,
      bpy=2,2'-bipyridine, Phen=1,10 phenanthroline) are synthesized and characterized
      using spectroscopic techniques (FT-IR, (1)H NMR, (13)C NMR, electronic absorption
      and emission) and elemental analysis data. The assembly of the complexes
      involving intramolecular H-bonding is displayed using corresponding crystal
      structure. Binding of the complexes separately with Calf Thymus DNA is monitored
      using UV-vis spectral titrations. The displacement of ethidium bromide (EB) bound
      to DNA by the complexes, in phosphate buffer solution (pH~7.2) is monitored using
      fluorescence spectral titrations. Nuclease activity of the complexes follow the
      order 4>3>1>2. The gel electrophoretic mobility assay measurement in presence of
      minor groove binder 4',6-diamidino-2-phenylindole (DAPI), suggests that complexes
      preferably bind with the minor groove of DNA. Topoisomerase I inhibitory activity
      of the complexes 3 and 4 inhibit topoisomerase I activity with IC50 values of 112
      and 87MUM respectively.

PMID- 26210017
TI  - (1)H NMR based metabolomics approach to study the toxic effects of dichlorvos on
      goldfish (Carassius auratus).
AB  - Dichlorvos (DDVP), one of the most widely used organophosphorus pesticides (OPs),
      has caused serious pollution in environment. In this study, (1)H nuclear magnetic
      resonance (NMR) based metabolomics approach combined with histopathological and
      immunohistochemical examination, and biochemical assays were used to investigate
      toxicities of DDVP on goldfish (Carassius auratus). After 10 days' exposure of
      DDVP at three dosages of 5.18, 2.59 and 1.73 mg/L, goldfish tissues (gill, brain,
      liver and kidney) and serum were collected. Histopathology revealed severe
      impairment of gills, livers and kidneys, and immunohistochemistry disclosed glial
      fibrillary acidic protein (GFAP) positive reactive astrocytes in brains.
      Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS
      DA) of NMR profiles disclosed that DDVP influenced many metabolites (glutamate,
      aspartate, acetylcholine, 4-aminobutyrate, glutathione, AMP and lactate in brain;
      glutathione, glucose, histamine in liver; BCAAs, AMP, aspartate, glutamate,
      riboflavin in kidney) dose-dependently, involved with imbalance of
      neurotransmitters, oxidative stress, and disorders of energy and amino acid
      metabolism. Several self-protection mechanisms concerning glutamate degradation
      and glutathione (GSH) redox system were found in DDVP intoxicated goldfish.

PMID- 26210018
TI  - Measurements of octanol-air partition coefficients, vapor pressures and
      vaporization enthalpies of the (E) and (Z) isomers of the 2-ethylhexyl 4
      methoxycinnamate as parameters of environmental impact assessment.
AB  - 2-Ethylhexyl 4-methoxycinnamate is one of the UVB blocking agents more widely
      used in a variety of industrial fields. There are more than one hundred
      industrial suppliers worldwide. Given the enormous annual consumption of
      octinoxate, problems that arise due to the accumulation of this compound in
      nature should be taken into consideration. The GC-RT was used in this work with
      the aim of determining the vapor pressure, enthalpies of vaporization and octanol
      air partition coefficient, for the BBP, DOP, E- and Z-EHMC esters. The results
      showed that Z-EHMC is almost five times more volatile than E-EHMC. Moreover, BBP,
      Z-EHMC and E-EHMC can be classified as substances with a relatively low mobility
      since they lie within the range of 8<logKOA<10 and -4<log(PL/Pa)<-2, while DOP
      lies in the range of logKOA>10 and log(PL/Pa)<-4, therefore, a low mobility can
      be expected. From these parameters, their particle-bound fraction and gas
      particle partition coefficient were also derived.

PMID- 26210019
TI  - Transport of sewage molecular markers through saturated soil column and effect of
      easily biodegradable primary substrate on their removal.
AB  - Pharmaceutical and personal care products (PPCPs) and artificial sweeteners (ASs)
      are emerging organic contaminants (EOCs) in the aquatic environment. The presence
      of PPCPs and ASs in water bodies has an ecologic potential risk and health
      concern. Therefore, it is needed to detect the pollution sources by understanding
      the transport behavior of sewage molecular markers in a subsurface area. The aim
      of this study was to evaluate transport of nine selected molecular markers
      through saturated soil column experiments. The selected sewage molecular markers
      in this study were six PPCPs including acetaminophen (ACT), carbamazepine (CBZ),
      caffeine (CF), crotamiton (CTMT), diethyltoluamide (DEET), salicylic acid (SA)
      and three ASs including acesulfame (ACF), cyclamate (CYC), and saccharine (SAC).
      Results confirmed that ACF, CBZ, CTMT, CYC and SAC were suitable to be used as
      sewage molecular markers since they were almost stable against sorption and
      biodegradation process during soil column experiments. In contrast, transport of
      ACT, CF and DEET were limited by both sorption and biodegradation processes and
      100% removal efficiency was achieved in the biotic column. Moreover, in this
      study the effect of different acetate concentration (0-100mg/L) as an easily
      biodegradable primary substrate on a removal of PPCPs and ASs was also studied.
      Results showed a negative correlation (r(2)>0.75) between the removal of some
      selected sewage chemical markers including ACF, CF, ACT, CYC, SAC and acetate
      concentration. CTMT also decreased with the addition of acetate, but increasing
      acetate concentration did not affect on its removal. CBZ and DEET removal were
      not dependent on the presence of acetate. 

PMID- 26210020
TI  - Growth, metabolism of Phanerochaete chrysosporium and route of lignin degradation
      in response to cadmium stress in solid-state fermentation.
AB  - This study examines the growth, metabolism of Phanerochaete chrysosporium (P.
      chrysosporium) and route of lignin degradation in response to cadmium (Cd) stress
      in solid-state fermentation of rice straw. Less living fungi biomass was found
      under Cd exposure, suggesting that Cd had strong toxicity to P. chrysosporium.
      The maximum values of lignin peroxidase and manganese peroxidase were 0.34 and
      5.21 U g(-1) at the Cd concentration of 32 mg kg(-1), respectively, lower than
      that in control, which indicated Cd stress would inhibit ligninolytic enzymes.
      The production of reactive oxygen species (ROS) including hydroxyl radicals (OH),
      superoxide anion radical (O2(-)) and hydrogen peroxide (H2O2) increased after Cd
      exposure. Higher concentration of oxalate was detected at high Cd concentrations.
      Cd stress also had influence on the rates of lignocelluloses degradation and the
      route of lignin degradation. Partial Cd could be removed by P. chrysosporium.

PMID- 26210021
TI  - Investigation into the feasibility of black carbon for remediation of nonylphenol
      polluted sediment through desorption kinetics after different order spiking.
AB  - The binding order of sorbent, sediment and organic compounds, as well as binding
      time is important factors determining the potential success of sorbent amendment,
      which should be considered when the practicability of sorbents was assessed. But
      until now, relevant research was rare. In this study, desorption in three
      practical conditions were simulated, by three mixing spiking orders among
      nonylphenol (NP), rice straw black carbon (RC) and sediment (the order of mixing
      spiking is (RC+Sediment)+NP, (Sediment+NP)+RC and (RC+NP)+Sediment, for situation
      I, II and III, respectively), to discuss the feasibility of using RC to remedy NP
      pollution. Results demonstrated that amendment of RC into sediment decreased
      desorption fractions of NP, and increased the resistant desorption fraction (Fr),
      implying strong affinity of NP to RC and efficient sequestration by RC. No
      significant differences were observed for desorption among the three fresh
      situations, meaning NP may be adsorbed on RC exterior surface sites and inter
      phase diffusion is faster than desorption. However, Fr for three aged situations
      was in the order: situation I<II<III, due to NP diffusion into the inter-pores or
      irreversible sorption sites of RC, reducing the releasing risk of NP. Regardless
      of time, Fr of three situations were all>0.5, suggesting RC is an effective
      sorbent for remedying NP pollution in the aquatic environment. Overall, we
      proposed a practical and analytical method for properly assessing the validity of
      a sorbent. 

PMID- 26210022
TI  - Reduced nitrification and abundance of ammonia-oxidizing bacteria in acidic soil
      amended with biochar.
AB  - Adding biochar into soils has potential to manipulate soil nitrification process
      due to its impacts on nitrogen (N) cycling, however, the exact mechanisms
      underlying the alteration of nitrification process in soils are still not clear.
      Nitrification in an acidic orchard soil amended with peanut shell biochar (PBC)
      produced at 400  degrees C was investigated. Nitrification was weakened by PBC
      addition due to the decreased NH4(+)-N content and reduced ammonia-oxidizing
      bacteria (AOB) abundance in PBC-amended soils. Adding phenolic compounds (PHCs)
      free biochar (PBC-P) increased the AOB abundance and the DGGE band number,
      indicating that PHCs remaining in the PBC likely reduced AOB abundance and
      diversity. However, PBC addition stimulated rape growth and increased N
      bioavailability. Overall, adding PBC could suppress the nitrification process and
      improve N bioavailability in the agricultural soils, and thus possibly mitigate
      the environmental negative impacts and improving N use efficiency in the acidic
      soils added with N fertilizer.

PMID- 26210023
TI  - Environmental fates of synthetic musks in animal and plant: An in vivo study.
AB  - As emerging contaminants, synthetic musks (SMs) cause worldwide concern due to
      their bioaccumulation in biota. However, the environmental fates of SMs in biota
      are poorly understood. Here, for the first time, the uptake and elimination
      behaviors, as well as the transferable capacities, of SMs in living edible biota
      (fish and aloe) were revealed. Fish muscle was approximately 100-2000 times more
      efficient in accumulating SMs than was aloe leaf, and nitro musks showed a higher
      bioaccumulation potential than did polycyclic musks in biota. In addition, the
      transferable capabilities of SMs by root uptake in aloe were poor. This
      investigation also showed that both nitro musks and polycyclic musks that
      accumulated in biota exhibited excellent elimination rates in clean water, and
      the elimination rates were greater than 78% and 80% in fish (3 d) and aloe (2 d),
      respectively. Furthermore, the calculated results suggest that SMs might act as
      chemosensitizers and enhance the accumulation of normally excluded toxicants in
      biota in a real aquatic environment.

PMID- 26210024
TI  - PGPR enhanced phytoremediation of petroleum contaminated soil and rhizosphere
      microbial community response.
AB  - The aim of this study was to investigate petroleum phytoremediation enhancement
      by plant growth promoting bacteria (PGPR), specifically the correlation between
      petroleum hydrocarbon fractions and bacterial community structure affected by
      remediation and PGPR inocula. Aged petroleum contaminated soil was remediated by
      tall fescue (Testuca arundinacea L.) inoculated with two PGPR strains.
      Hydrocarbon degradation was measured by GC-MS (Gas-chromatography Mass
      spectrometer) based on carbon fraction numbers (C8-C34). Changes in bacterial
      community structure were analyzed by high-throughput pyrosequencing of 16s rRNA.
      PGPR inoculation increased tall fescue biomass and petroleum hydrocarbons were
      removed in all the treatments. Maximum hydrocarbon removal, particular high
      molecular weight (C21-C34) aliphatic hydrocarbons (AHs) and polycyclic aromatic
      hydrocarbons (PAHs), was observed in tall fescue inoculated with PGPR. The
      relative abundance of phyla gamma-proteobacteria and Bacteroidetes increased
      after different treatments compared with controls. Moreover, a bacterial guild
      mainly comprising the genera Lysobacter, Pseudoxanthomonas, Planctomyces,
      Nocardioides, Hydrogenophaga, Ohtaekwangia was found to be positively correlated
      with C21-C34 petroleum hydrocarbons fractions removal by RDA analysis, implying
      that petroleum degradation was unrelated to bacterial community diversity but
      positively correlated with specific petroleum degraders and biosurfactant
      producers. 

PMID- 26210025
TI  - Estimating the mean and standard deviation of environmental data with below
      detection limit observations: Considering highly skewed data and model
      misspecification.
AB  - In environmental studies, concentration measurements frequently fall below
      detection limits of measuring instruments, resulting in left-censored data. Some
      studies employ parametric methods such as the maximum likelihood estimator (MLE),
      robust regression on order statistic (rROS), and gamma regression on order
      statistic (GROS), while others suggest a non-parametric approach, the Kaplan
      Meier method (KM). Using examples of real data from a soil characterization study
      in Montreal, we highlight the need for additional investigations that aim at
      unifying the existing literature. A number of studies have examined this issue;
      however, those considering data skewness and model misspecification are rare.
      These aspects are investigated in this paper through simulations. Among other
      findings, results show that for low skewed data, the performance of different
      statistical methods is comparable, regardless of the censoring percentage and
      sample size. For highly skewed data, the performance of the MLE method under
      lognormal and Weibull distributions is questionable; particularly, when the
      sample size is small or censoring percentage is high. In such conditions, MLE
      under gamma distribution, rROS, GROS, and KM are less sensitive to skewness.
      Related to model misspecification, MLE based on lognormal and Weibull
      distributions provides poor estimates when the true distribution of data is
      misspecified. However, the methods of rROS, GROS, and MLE under gamma
      distribution are generally robust to model misspecifications regardless of
      skewness, sample size, and censoring percentage. Since the characteristics of
      environmental data (e.g., type of distribution and skewness) are unknown a
      priori, we suggest using MLE based on gamma distribution, rROS and GROS. 

PMID- 26210026
TI  - Leaching of biocides from polymer renders under wet/dry cycles--Rates and
      mechanisms.
AB  - In this study it was tested, which mechanism for the transport of biocides in
      polymeric renders is more relevant: (1) evaporative transports (meaning there is
      a flow of water through the material due to evaporation on the surface), which
      transports also the biocides to the surface, (2) transport through the polymer
      and (3) transport through water filled pores. It turned out that under the
      experimental conditions evaporative transport was not relevant, while transport
      through soaked (constantly wetted) renders was considerably faster than by other
      means. Additionally it turned out that also the equilibria were influenced by the
      water content. Differences in equilibria can be up to factor 10 between
      constantly wetted (soaked) and un-wetted materials. The two tested materials (one
      silicone and one acrylate render) had significantly different leaching behavior
      concerning equilibria and dynamics of mass flows, but for both the pre-wetted
      materials leached most. 

PMID- 26210027
TI  - Topical autologous serum promotes enucleation wound healing in retinoblastoma
      patients.
AB  - Two retinoblastoma patients underwent uneventful enucleations while undergoing
      perioperative chemotherapy. In both cases the postoperative course was
      complicated by poor conjunctival wound healing. Administration of topical
      autologous serum was associated with wound healing and conjunctivalization of
      these wounds. 

PMID- 26210028
TI  - Comparative study on power generation of dual-cathode microbial fuel cell
      according to polarization methods.
AB  - Microbial fuel cells (MFCs) exist in various forms depending on the type of
      pollutant to be removed and the expected performance. Dual-cathode MFCs, with
      their simple structure, are capable of removing both organic matter and nitrogen.
      Moreover, various methods are available for the collection of polarization data,
      which can be used to calculate the maximum power density, an important factor of
      MFCs. Many researchers prefer the method of varying the external resistance in a
      single-cycle due to the short measurement time and high accuracy. This study
      compared power densities of dual-cathode MFCs in a single-cycle with values
      calculated over multi-cycles to determine the optimal polarization method.
      External resistance was varied from high to low and vice versa in the single
      cycle, to calculate power density. External resistance was organized in
      descending order with initial start-up at open circuit voltage (OCV), and then it
      was organized in descending order again after the initial start-up at 1000 Omega.
      As a result, power density was underestimated at the anoxic cathode when the
      external resistance was varied from low to high, and overestimated at the aerobic
      cathode and anoxic cathode when external resistance at OCV was reduced following
      initial start-up. In calculating the power densities of dual-cathode MFCs, this
      paper recommends the method of gradually reducing the external resistance after
      initial start-up with high external resistance. 

PMID- 26210029
TI  - Degradation of (14)C-labeled few layer graphene via Fenton reaction: Reaction
      rates, characterization of reaction products, and potential ecological effects.
AB  - Graphene has attracted considerable commercial interest due to its numerous
      potential applications. It is inevitable that graphene will be released into the
      environment during the production and usage of graphene-enabled consumer
      products, but the potential transformations of graphene in the environment are
      not well understood. In this study, (14)C-labeled few layer graphene (FLG)
      enabled quantitative measurements of FLG degradation rates induced by the
      iron/hydrogen peroxide induced Fenton reaction. Quantification of (14)CO2
      production from (14)C-labeled FLG revealed significant degradation of FLG after 3
      days with high H2O2 (200 mmol L(-1)) and iron (100 MUmol L(-1)) concentrations
      but substantially lower rates under environmentally relevant conditions (0.2-20
      mmol L(-1) H2O2 and 4 MUmol L(-1) Fe(3+)). Importantly, the carbon-14 labeling
      technique allowed for quantification of the FLG degradation rate at
      concentrations nearly four orders of magnitude lower than those typically used in
      other studies. These measurements revealed substantially faster degradation rates
      at lower FLG concentrations and thus studies with higher FLG concentrations may
      underestimate the degradation rates. Analysis of structural changes to FLG using
      multiple orthogonal methods revealed significant FLG oxidation and multiple
      reaction byproducts. Lastly, assessment of accumulation of the degraded FLG and
      intermediates using aquatic organism Daphnia magna revealed substantially
      decreased body burdens, which implied that the changes to FLG caused by the
      Fenton reaction may dramatically impact its potential ecological effects. 

PMID- 26210030
TI  - Integrating organic micropollutant removal into tertiary filtration: Combining
      PAC adsorption with advanced phosphorus removal.
AB  - Direct addition of powdered activated carbon (PAC) to a deep-bed filter was
      investigated at pilot-scale as a single advanced treatment stage for simultaneous
      removal of organic micropollutants (OMPs) and phosphorus from secondary effluent.
      PAC doses of 10-50 mg/L were assessed with regard to their impacts on filter
      performance and removal of 15 selected OMPs over a period of 18 months. The PAC
      was effectively retained by the filter and had no negative effect on filter head
      loss. Filter runtime until particle breakthrough depended mainly on coagulant
      dose and did not decrease significantly due to the additional PAC load. Removal
      of suspended solids and phosphorus by coagulation was effective independent of
      the PAC dose. A PAC dose of 35 mg/L PAC was suitable to remove well-adsorbing
      OMPs (e.g. carbamazepine, diclofenac) by >80% and medium adsorbing OMPs (e.g.
      primidone, sulfamethoxazole) by 50-80%. Median removals were 50-80% for well
      adsorbing and 30-50% for medium adsorbing OMPs with 20 mg/L PAC. Abatement of all
      OMPs was low (<50%) with 10 mg/L PAC, possibly because of the high effluent
      organic matter content (median dissolved organic carbon (DOC) concentrations of
      11.2 mg/L). In addition to adsorptive removal, relevant concentration decreases
      of certain OMPs (e.g. 4-formylaminoantipyrine) were attributed to biological
      transformation in the filter. Adsorption onto accumulating PAC in the top layer
      of the filter bed led to improved OMP adsorption with increasing filter runtime.
      The comparison of OMP removal in the pilot filter with laboratory adsorption
      tests demonstrates that batch test results can be applied to estimate adsorptive
      OMP removal in real applications. 

PMID- 26210031
TI  - Anaerobic ammonium oxidation in traditional municipal wastewater treatment plants
      with low-strength ammonium loading: Widespread but overlooked.
AB  - Occurrence of anaerobic ammonium oxidation (anammox) in marine and freshwater
      systems has greatly changed our understanding of global nitrogen (N) cycle and
      promoted the investigation of the role and ecological features of anammox in
      anthropogenic ecosystems. This study focused on the spatio-temporal abundance,
      activity, and biodiversity of anammox bacteria in full-scale municipal wastewater
      treatment plants (WWTPs) via traditional nitrification/denitrification route with
      low-strength ammonium loading. The anammox bacteria were detected in all the
      treatment units at the five WWTPs tested, even in aerobic zones (dissolved oxygen
      >2 mg L(-1)) with abundance of 10(5)-10(7) hydrazine synthase (hzs) gene copies
      g(-1). The (15)N-isotope tracing technology revealed that the anammox rates in
      WWTPs ranged from 0.08 to 0.36 MUmol N g(-1) h(-1) in winter and 0.12-1.20 MUmol
      N g(-1) h(-1) in summer with contributions of 2.05-6.86% and 1.71-7.26% to N2
      production, respectively. The diversity of anammox bacteria in WWTPs was
      distributed over only two genera, Brocadia and Kuenenia. Additionally, the
      exploration of potential interspecies relationships indicated that ammonia
      oxidation bacteria (AOB) was the major nitrite-substrate producer for anammox
      during nitrification, while Nitrospira, a nitrite oxidation bacteria (NOB), was
      the potential major competitor for nitrite. These results suggested the
      contribution of N-removal by the widespread of anammox has been overlooked in
      traditional municipal WWTPs, and the ecological habitats of anammox bacteria in
      anthropogenic ecosystems are much more abundant than previously assumed. 

PMID- 26210032
TI  - Methamphetamine and ketamine use in major Chinese cities, a nationwide
      reconnaissance through sewage-based epidemiology.
AB  - Sewage-based epidemiology was applied to examine geographic variations in
      methamphetamine (METH) and ketamine (KET) use in China. Influent and effluent
      wastewater samples were collected from 36 sewage treatment plants (STPs) in 18
      major cities that cover all the geographic regions of the country. Mean METH
      loads of the cities ranged from 12.5 +/- 14.9 to 181.2 +/- 6.5 mg/1000 inh/d,
      whereas mean KET loads ranged from <0.2 to 89.6 +/- 27.4 mg/1000 inh/d. No clear
      geographical pattern was observed in METH use, although slightly lower use in
      north and east China relative to other regions can be suggested. In contrast, an
      overall increasing trend from the north to the south was evident for KET loads.
      Apparent METH removal was greater than 80% at most STPs, whereas KET removal was
      less than 50% at most STPs and was even negative (i.e., measured effluent
      concentrations were greater than influent concentrations) at a significant number
      of STPs. Results in Beijing, Shanghai, and Shenzhen indicate that METH use in
      China may have increased substantially since 2012, whereas KET use did not
      significantly change, if not decreased. Comparison between seizures and estimated
      consumptions reveals that seizures in most Chinese provinces are far less than
      consumptions. In several provinces (e.g., Guangdong and Yunan), however, seizures
      were found to exceed consumptions, indicating that a significant fraction of METH
      and KET seized in these provinces is destined for consumption in other places. 

PMID- 26210033
TI  - From consumption to harvest: Environmental fate prediction of excreted ionizable
      trace organic chemicals.
AB  - Excreted trace organic chemicals, e.g., pharmaceuticals and biocides, typically
      undergo incomplete elimination in municipal wastewater treatment plants (WWTPs)
      and are released to surface water via treated effluents and to agricultural soils
      through sludge amendment and/or irrigation with freshwater or reclaimed
      wastewater. Recent research has shown the tendency for these substances to
      accumulate in food crops. In this study, we developed and applied a simulation
      tool to predict the fate of three ionizable trace chemicals (triclosan-TCS,
      furosemide-FUR, ciprofloxacin-CIP) from human consumption/excretion up to the
      accumulation in soil and plant, following field amendment with sewage sludge or
      irrigation with river water (assuming dilution of WWTP effluent). The simulation
      tool combines the SimpleTreat model modified for fate prediction of ionizable
      chemicals in a generic WWTP and a recently developed dynamic soil-plant uptake
      model. The simulation tool was tested using country-specific (e.g.,
      consumption/emission rates, precipitation and temperature) input data. A Monte
      Carlo-based approach was adopted to account for the uncertainty associated to
      physico-chemical and biokinetic model parameters. Results obtained in this study
      suggest significant accumulation of TCS and CIP in sewage sludge (1.4-2.8 mg
      kgDW(-1)) as compared to FUR (0.02-0.11 mg kgDW(-1)). For the latter substance,
      more than half of the influent load (60.1%-72.5%) was estimated to be discharged
      via WWTP effluent. Specific emission rates (g ha(-1) a(-1)) of FUR to soil via
      either sludge application or irrigation were up to 300 times lower than for TCS
      and CIP. Nevertheless, high translocation potential to wheat was predicted for
      FUR, reaching concentrations up to 4.3 MUg kgDW(-1) in grain. Irrigation was
      found to enhance the relative translocation of FUR to plant (45.3%-48.9% of
      emission to soil), as compared to sludge application (21.9%-27.6%). A comparison
      with peer-reviewed literature showed that model predictions were close to
      experimental data for elimination in WWTP, concentrations in sewage and sludge
      and bioconcentration factors (BCFs) in plant tissues, which showed however a
      large variability. The simulation tool presented here can thus be useful for
      priority setting and for the estimation of human exposure to trace chemicals via
      intake of food crops. 

PMID- 26210034
TI  - Numerical study identifying the factors causing the significant underestimation
      of the specific discharge estimated using the modified integral pumping test
      method in a laboratory experiment.
AB  - A three-dimensional finite element model is constructed to simulate the
      experimental conditions presented in a paper published in this journal [Goltz et
      al., 2009. Validation of two innovative methods to measure contaminant mass flux
      in groundwater. Journal of Contaminant Hydrology 106 (2009) 51-61] where the
      modified integral pumping test (MIPT) method was found to significantly
      underestimate the specific discharge in an artificial aquifer. The numerical
      model closely replicates the experimental configuration with explicit
      representation of the pumping well column and skin, allowing for the model to
      simulate the wellbore flow in the pumping well as an integral part of the porous
      media flow in the aquifer using the equivalent hydraulic conductivity approach.
      The equivalent hydraulic conductivity is used to account for head losses due to
      friction within the wellbore of the pumping well. Applying the MIPT method on the
      model simulated piezometric heads resulted in a specific discharge that
      underestimates the true specific discharge in the experimental aquifer by 18.8%,
      compared with the 57% underestimation of mass flux by the experiment reported by
      Goltz et al. (2009). Alternative simulation shows that the numerical model is
      capable of approximately replicating the experiment results when the equivalent
      hydraulic conductivity is reduced by an order of magnitude, suggesting that the
      accuracy of the MIPT estimation could be improved by expanding the physical
      meaning of the equivalent hydraulic conductivity to account for other factors
      such as orifice losses in addition to frictional losses within the wellbore.
      Numerical experiments also show that when applying the MIPT method to estimate
      hydraulic parameters, use of depth-integrated piezometric head instead of the
      head near the pump intake can reduce the estimation error resulting from well
      losses, but not the error associated with the well not being fully screened. 

PMID- 26210035
TI  - Characterization of a thermostable and alkali-stable alpha-amylase from deep-sea
      bacterium Flammeovirga pacifica.
AB  - A thermostable alpha-amylase (designated as Amy16) has been previously identified
      in Flammeovirga pacifica isolated from deep-sea sediments. The DNA sequence of
      Amy16 exhibited no significant similarity with those of any known protein,
      including the glycoside hydrolases. Amino acid sequence analysis revealed that
      Amy16 belonged to GH13 family and possessed a conserved DXEXD motif, which was
      essential for its hydrolysis activities. The recombinant Amy16 purified with
      Ni(+) affinity column after its heterologous expression in Escherichia coli cells
      was most active at 50  degrees C and retained more than 81% of its initial
      activity after incubation at 60  degrees C for 20 min. The optimal pH for Amy16
      was determined to be 6.5, and a good tolerance to alkaline environment was
      observed. Low concentration of Mg(2+), Sr(2+), Na(+) and K(+) slightly increased
      the activity of Amy16. Results of thin layer chromatography experiments revealed
      that Amy16 was able to hydrolyse starch into maltose in a time-dependent manner,
      suggesting that Amy16 is a liquid-type endoenzyme with starch hydrolysis
      activities. Therefore, our study presented thermostable and alkali-stable Amy16,
      which may be suitable for use as an additive in detergents.

PMID- 26210036
TI  - Synthesis of highly substituted carboxymethyl cellulose depending on cellulose
      particle size.
AB  - Corn husk is an abundant agricultural waste. It has great potential for use as a
      cellulose source for the production of carboxymethyl cellulose (CMC). The
      chemical composition of corn husk, such as cellulose, hemicelluloses, lignin,
      fatty and waxy matter, pectic matter and aqueous extract was determined. The
      cellulose extracted from corn husk was carboxymethylated using sodium hydroxide
      (NaOH) and monochloroacetic acid (MCA), in aqueous ethanolic medium, under
      heterogeneous conditions. The carboxymethylation reaction was optimized as to the
      NaOH concentration, MCA concentration, reaction temperature, reaction time and
      cellulose particle size. The degree of substitution (DS) was determined with
      respect to the reaction conditions using chemical methods. The produced CMC was
      identified by FTIR and the crystallinity of the CMC was determined by XRD. The
      CMC product had an optimized DS of 2.41 and the optimal conditions for
      carboxymethylation were NaOH concentration, 7.5 mol/L; MCA concentration, 12
      mol/L; reaction temperature, 55  degrees C; reaction time, 3.5 h and cellulose
      particle size, 74 MUm. These optimization factors allowed to prepare highly
      substituted CMC with higher yield, 2.40 g/g, providing plenty of opportunities
      for its many applications.

PMID- 26210037
TI  - Brain delivery of buspirone hydrochloride chitosan nanoparticles for the
      treatment of general anxiety disorder.
AB  - The present work discusses the preparation, characterization and in vivo
      evaluation of thiolated chitosan nanoparticles (TCS-NPs) of buspirone
      hydrochloride (BUH) for brain delivery through intranasal route. TCS NPs were
      prepared by ionic gelation method and characterized for various parameters. The
      NPs formed were having particle size of 226.7+/-2.52nm with PDI 0.483+/-0.031.
      Drug entrapment efficiency (EE) and loading capacity (LC) were found to be
      81.13+/-2.8 and 49.67+/-5.5%. The cumulative percentage drug permeation through
      nasal mucosa was 76.21%. Bioadhesion study carried out on porcine mucin and
      showed a bioadhesion efficiency of 90.218+/-0.134%. Nose-to-brain delivery of
      placebo NPs was investigated by confocal laser scanning microscopy (CLSM)
      technique using rhodamine-123 as a marker. The brain concentration achieved after
      intranasal administration of TCS-NPs was 797.46+/-35.76ng/ml with tmax 120min
      which was significantly higher than achieved after intravenous administration on
      BUH solution 384.15+/-13.42ng/ml and tmax of 120min and intranasal administration
      of BUH solution 417.77+/-19.24ng/ml and tmax 60min. 

PMID- 26210038
TI  - Kinetic and thermodynamic studies of a novel acid protease from Aspergillus
      foetidus.
AB  - The kinetics of a thermostable extracellular acid protease produced by an
      Aspergillus foetidus strain was investigated at different pH, temperatures and
      substrate concentrations. The enzyme exhibited maximal activity at pH 5.0 and 55
      degrees C, and its irreversible deactivation was well described by first-order
      kinetics. When temperature was raised from 55 to 70 degrees C, the deactivation
      rate constant increased from 0.018 to 5.06h(-1), while the half-life decreased
      from 37.6 to 0.13h. The results of activity collected at different temperatures
      were then used to estimate, the activation energy of the hydrolysis reaction
      (E*=19.03kJ/mol) and the standard enthalpy variation of reversible enzyme
      unfolding (DeltaH degrees U=19.03kJ/mol). The results of residual activity tests
      carried out in the temperature range 55-70 degrees C allowed estimating the
      activation energy (E(*)d=314.12kJ/mol), enthalpy (311.27<=(DeltaH degrees
      d<=311.39kJ/mol), entropy (599.59<=DeltaS(*)d<=610.49kJ/mol K) and Gibbs free
      energy (103.18<=DeltaG(*)d<=113.87kJ/mol) of the enzyme irreversible
      denaturation. These thermodynamic parameters suggest that this new protease is
      highly thermostable and could be important for industrial applications. To the
      best of our knowledge, this is the first report on thermodynamic parameters of an
      acid protease produced by A. foetidus. 

PMID- 26210039
TI  - Protocols to test the activity of antimicrobial peptides against the honey bee
      pathogen Paenibacillus larvae.
AB  - Paenibacillus larvae is the causal agent of the honey bee disease American
      Foulbrood. Two enhanced protocols that allow the activity of antimicrobial
      peptides to be tested against P. larvae are presented. Proof of principle
      experiments demonstrate that the honey bee antimicrobial peptide defensin 1 is
      active in both assays. 

PMID- 26210040
TI  - Simultaneous detection of 33 Streptococcus suis serotypes using the luminex
      xTAG(r) assayTM.
AB  - We report the development and evaluation of a serotype-specific xTAG luminex
      assay (SSA) that allows detection of the 33 serotypes of Streptococcus suis (S.
      suis). This assay is based on wzy gene targets directly involved in the cps
      biosynthesis and can be completed 40 min post-PCR amplification. The assay
      correctly and specifically identified the serotype of all 209 isolates tested, in
      comparison with two serotyping multiplex PCR methods previously developed. The
      sensitivity was higher than that of the previously described methods. The SSA
      system described here provides an easy-to-use, high-throughput system for rapid
      detection of S. suis serotypes.

PMID- 26210041
TI  - Measuring Therapy-Induced Peripheral Neuropathy: Preliminary Development and
      Validation of the Treatment-Induced Neuropathy Assessment Scale.
AB  - Various sensory and motor effects are associated with cancer treatment-induced
      peripheral neuropathy. The current method for capturing the multifaceted nature
      of neuropathy includes a combination of objective tests, clinician evaluation,
      and subjective patient report, an approach that is often not logistically
      feasible, especially for multisite trials. We report the performance of a brief
      yet comprehensive, easily administered measure, the Treatment-Induced Neuropathy
      Assessment Scale (TNAS), for assessing the severity and course of neuropathy
      across various cancer treatments. Data were derived from 4 longitudinal or cross
      sectional patient cohorts (N = 573). Patients with multiple myeloma treated
      primarily with bortezomib and patients with colorectal cancer receiving
      oxaliplatin evaluated candidate items. Cognitive debriefing showed that all items
      were easy to understand, and this preliminary TNAS demonstrated reliability,
      validity, and sensitivity. Numbness/tingling was the most severe item, regardless
      of therapeutic agent. Although numbness and general pain were moderately
      correlated, patients perceived them as distinct. Most TNAS items were more severe
      at follow-up, demonstrating the sensitivity of the instrument to accumulating
      dose. The TNAS will be refined with further patient input, with final
      psychometric evaluation conducted in a new patient sample receiving treatments
      known to be associated with peripheral neuropathy. The nonpainful component of
      neuropathy may be more disabling than the pain component. PERSPECTIVE: Our data
      suggest that the nonpainful components of neuropathy may be more disabling than
      the pain component during cancer treatment. Here we report data on sensory and
      motor symptoms reported by patients receiving neurotoxic cancer therapy, and we
      detail the development of a neuropathy assessment scale that follows regulatory
      guidance for patient-reported outcomes.

PMID- 26210043
TI  - A rational approach to select immunogenic peptides that induce IFN-gamma response
      against Toxoplasma gondii in human leukocytes.
AB  - The ideal vaccine to prevent toxoplasmosis in humans would comprise antigens that
      elicit a protective T cell type 1 response with high IFN-gamma production. Here,
      we report the use of a bioinformatics pipeline to discover peptides based on
      biochemical characteristics that predict strong IFN-gamma response by human
      leukocytes. We selected peptide sequences that previously were reported to induce
      IFN-gamma to identify the biophysical characteristics that will predict HLA-A*02
      high-affinity epitopes. We found that the protein motif pattern FL...L..[VL] was
      common in previously reported highly immunogenic sequences. We have selected new
      peptides with a length of 9 residues with affinities from 2 to 21 nM with peptide
      signal and transmembrane domains and predicted to be cleaved at the proteasome to
      perform ELISPOT assays with human leukocytes. Within 9 peptides with the highest
      scores for IFN-gamma production, four peptides elicited IFN-gamma levels in a
      range from 252 to 1763 SFC/1e6. Our pipeline uncovered Toxoplasma proteins with
      peptides that are processed by MHC class 1 in humans. Our results suggest that
      our rational strategy for the selection of immunogenic epitopes could be used to
      select peptides as candidates for inclusion in epitope-based vaccines.

PMID- 26210042
TI  - Exhaustion-related changes in cardiovascular and cortisol reactivity to acute
      psychosocial stress.
AB  - Prior findings indicate that individuals scoring high on vital exhaustion show a
      dysfunctional stress response (DSR), that is, reduced cortisol reactivity and
      habituation to psychosocial stressors. The main aim of the present study was to
      examine whether a DSR may be a vulnerability factor in exhaustion disorder (ED).
      We examined whether a DSR is present during the early stages of ED, and still is
      present after recovery. Three groups were studied: 1. Former ED patients (n=14);
      2. persons who during the past 6 month had experienced stress at work and had a
      Shirom-Melamed Burnout Questionnaire (SMBQ) score over 3.75, considered to
      indicate a pre-stage of ED (n=17); 3. persons who had not experienced stress at
      work during the past 6 months and had a SMBQ score below 2.75 (n=20). The
      participants were exposed twice to a virtual version of the Trier Social Stress
      Test (V-TSST), during which salivary cortisol samples were collected. In
      addition, high frequency heart rate variability (HF-HRV), heart rate (HR), t-wave
      amplitude (TWA), and alpha-amylase were assessed to examine stress reactivity and
      habituation in the autonomic nervous system (ANS). The initial analyses showed
      clear hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system
      (SNS) activations in both V-TSST sessions, together with habituation of cortisol
      and heart rate in the second session, but without any significant group
      differences. However, the former ED patients showed considerable variation in
      self-reported signs of exhaustion (SMBQ). This led us to assign former ED
      patients with lower ratings into the low SMBQ group (LOWS) and those with higher
      ratings to the high SMBQ group (HIGHS). When repeating the analyses a different
      picture emerged; the HIGHS showed a lower cortisol response to the V-TSST than
      did the LOWS. Both groups' cortisol response habituated to the second V-TSST
      session. The ANS responses did not differ between the two groups. Thus, persons
      in a pre-stage of ED and unrecovered former ED patients showed signs of DSR, in
      contrast to healthy controls and recovered former ED patients. The results may be
      interpreted as indicating that DSR in the HPA axis is present early on in the
      stress process, but subsides after successful recovery.

PMID- 26210044
TI  - Heat killed multi-serotype Shigella immunogens induced humoral immunity and
      protection against heterologous challenge in rabbit model.
AB  - Recently we have shown the homologous protective efficacy of heat killed multi
      serotype Shigella (HKMS) immunogens in a guinea pig colitis model. In our present
      study, we have advanced our research by immunizing rabbits with a reduced number
      of oral doses and evaluating the host's adaptive immune responses. The duration
      of immunogenicity and subsequently protective efficacy was determined against
      wild type heterologous Shigella strains in a rabbit luminal model. After three
      successive oral immunizations with HKMS immunogens, serum and lymphocyte
      supernatant antibody titer against the heterologous shigellae were reciprocally
      increased and remained at an elevated level up to 180 days. Serogroup and
      serotype specific O-antigen of lipopolysaccharide and immunogenic proteins of
      heterologous challenge strains were detected by immunoblot assay. Up-regulation
      of IL-12p35, IFN-gamma and IL-10 mRNA expression was detected in immunized rabbit
      peripheral blood mononuclear cells (PBMC) after stimulation with HKMS in vitro.
      HKMS-specific plasma cell response was confirmed by production of a relatively
      higher level of HKMS-specific IgG in immunized PBMC supernatant compared to
      control group. Furthermore, the immunized groups of rabbits exhibited complete
      protection against wild type heterologous shigellae challenge. Thus HKMS
      immunogens induced humoral and Th1-mediated adaptive immunity and provided
      complete protection in a rabbit model. These immunogens could be a broad spectrum
      non-living vaccine candidate for human use in the near future. 

PMID- 26210045
TI  - Hyaluronan carried by tumor-derived microvesicles induces IL-10 production in
      classical (CD14++CD16-) monocytes via PI3K/Akt/mTOR-dependent signalling pathway.
AB  - Tumor-derived microvesicles (TMV) can mimic effects of tumor cells leading to an
      increased anti-inflammatory cytokine production, such as interleukin 10 (IL-10),
      by tumor-infiltrating monocytes and macrophages. Yet, the mechanism of IL-10
      induction by TMV in monocytes remains unclear. The co-incubation of TMV derived
      from the human pancreas carcinoma cell line (HPC-4) with human monocytes resulted
      in a nearly 30-fold increase in IL-10 protein production. This effect operates at
      the level of transcription since monocytes transduced with an adenovirus
      containing IL-10-promoter luciferase reporter gene showed a 5-fold induction of
      luciferase activity after treatment with TMV. Since tumor cells can express
      hyaluronan (HA), which participates in tumor invasion and metastases, we have
      tested its effect on IL-10 expression. We showed that HA at the concentration of
      100MUg/ml induces IL-10 protein expression and the IL-10 promoter activation in
      monocytes. Moreover, hyaluronidase treatment of TMV reduced IL-10 protein
      production by 50% and promoter activity by 40%. Inhibitors of the PI3K/Akt/mTOR
      pathway reduced both, TMV-induced IL-10 promoter activity and protein production,
      and the same was observed in monocytes when stimulated by HPC-4 cells or HA.
      Inhibition of PI3K activity down-regulated phosphorylation of the Akt and (to a
      lesser extent) mTOR proteins in monocytes following TMV or HA stimulation. When
      comparing monocyte subsets, TMV induced IL-10 protein and mRNA synthesis only in
      classical CD14++CD16- but not in CD16-positive monocytes. Our data show that TMV
      induce IL-10 synthesis in human classical monocytes via HA, which, in turn,
      activates the PI3K/Akt/mTOR pathway.

PMID- 26210046
TI  - Salmonella impairs CD8 T cell response through PD-1: PD-L axis.
AB  - We have shown that Salmonella remains for a long period of time within B cells,
      plasma cells, and bone marrow B cell precursors, which might allow persistence
      and dissemination of infection. Nonetheless, how infected cells evade CD8 T cell
      response has not been characterized. Evidence indicates that some pathogens
      exploit the PD-1: PD-L (PD-L1 and PD-L2) interaction to inhibit CD8 T cells
      response to contribute the chronicity of the infection. To determine whether the
      PD-1: PD-L axis plays a role during Salmonella infection; we evaluated PD-1
      expression in antigen-specific CD8 T cells and PD-1 ligands in Salmonella
      infected cells. Our results show that infected B cells and macrophages express
      continuously co-stimulatory (CD40, CD80, and CD86) and inhibitory molecules (PD
      L1 and PD-L2) in early and late stages of chronic Salmonella infection, while
      antigen-specific CD8 T cells express in a sustained manner PD-1 in the late
      stages of infection. Blocking this axis restores the ability of the CD8 T cells
      to proliferate and eliminate primary infected APCs. Therefore, a continuous PD-1:
      PDL interaction might be a mechanism employed by Salmonella to negatively
      regulate Salmonella-specific CD8 T cell cytotoxic response in order to remain
      within the host for a long period of time. 

PMID- 26210047
TI  - New mode for measuring axial length with an optical low-coherence reflectometer
      in eyes with dense cataract.
AB  - PURPOSE: To evaluate a new algorithm for measuring eyes with dense cataract using
      a biometer based on optical low-coherence reflectometry (OLCR). SETTING: Shammas
      Eye Medical Center, Lynwood, California, USA, and Augenarztpraxis EYEC, Bern,
      Switzerland. DESIGN: Cross-sectional retrospective study. METHODS: Data were
      collected from 2 sites where the new Dense Cataract Measurement mode for the OLCR
      optical biometer (Lenstar LS 900) had been implemented. Related ultrasound (US)
      data for patients whose eyes could not be measured with optical biometry were
      also collected where available. The percentage of eyes that were measurable in
      the new mode that were not measurable in the standard mode was calculated. The
      quality of the measurements by the new mode was evaluated using postoperative
      axial length measurements and/or concurrent US measurements, where available.
      RESULTS: Data for 4791 eyes were available for analysis. Axial length measurement
      was possible using the standard algorithm in 94.4% of cases. The use of the new
      mode allowed for measurement of an additional 4.0% of cases, a statistically
      significant increase (P < .001). Comparisons of AL measurements with concurrent
      US or postoperative optical biometry showed high correlations, with the 95%
      limits of agreement of -0.47 to +0.29 mm, similar to results for standard
      measurements. CONCLUSIONS: The new measurement mode of the OLCR system provided a
      significant increase in the number of eyes that could be measured with optical
      biometry. Axial length measurements using the new mode appeared as reliable as
      those made using the standard measurement mode. FINANCIAL DISCLOSURE: No author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 26210049
TI  - Open ring-shaped guider for circular continuous curvilinear capsulorhexis during
      cataract surgery.
AB  - We describe a new type of open-loop caliper for capsulorhexis during cataract
      surgery. This tool, which is made of poly(methyl methacrylate), can optimize
      capsulorhexis shape, size, and centration. One of the strengths of this tool,
      which derives from the open-loop design, is its ease of insertion and removal via
      a small incision site compared with other calipers used for capsulorhexis. The
      caliper is positioned on the anterior capsule after the anterior chamber is
      filled with an ophthalmic viscosurgical device and removed after creation of the
      continuous curvilinear capsulorhexis. The caliper enables the surgeon to achieve
      an ideal capsulorhexis and promotes long-lasting circularity. FINANCIAL
      DISCLOSURE: Dr. Joo is one of the inventors on the patent filed by the Catholic
      University of Korea covering details in this manuscript. Dr. Lee has no financial
      or proprietary interest in any material or method mentioned.

PMID- 26210048
TI  - Erufosine, a phosphoinositide-3-kinase inhibitor, to mitigate posterior capsule
      opacification in the human capsular bag model.
AB  - PURPOSE: To determine whether erufosine alone or erufosine-loaded intraocular
      lenses (IOLs) can inhibit growth of human lens epithelial cells after a single
      administration in the human capsular bag model. SETTING: Laboratory for Cell
      Biology, Department of Ophthalmology, Ludwig-Maximilians-University, Munich,
      Germany. DESIGN: Experimental study. METHODS: Sixteen human cadaver eyes had sham
      cataract surgery. The capsular bag was transferred into cell culture. The tissue
      was exposed to the half maximum inhibitory concentrations of erufosine alone for
      72 hours; solvent-only tissue served as a control. Erufosine is a potent
      inhibitor of phosphoinositide-3-kinase, a downstream kinase with major
      implications in posterior capsule opacification (PCO) pathogenesis. The IOLs were
      soaked with erufosine and implanted in the capsular bags; unsoaked IOLs served as
      controls. For both settings, the time until confluence of the capsular bag was
      measured. Cell growth was observed and photodocumented. RESULTS: Erufosine as a
      single therapeutic agent increased the time until confluence of the capsular bag,
      but not significantly compared with the control. When IOLs were soaked with
      erufosine, a long-term prophylactic effect was observed in this organ model for
      PCO, which is known to closely reflect the clinical situation. CONCLUSION:
      Erufosine-soaked IOLs effectively inhibited PCO formation as seen in long-term
      organ culture and might become of clinical relevance. FINANCIAL DISCLOSURES: Drs.
      Kampik and Eibl-Lindner are inventors of IOLs treated with alkylphosphocholines
      for pharmacological after-cataract prophylaxis, patent international application
      PCT/EP2010/051490. No other author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 26210050
TI  - Optic capture in complicated laser-assisted cataract surgery.
AB  - An 84-year-old woman had routine laser-assisted cataract surgery with anterior
      laser capsulotomy and lens fragmentation. During hydropolishing of the posterior
      capsule, an unexpected posterior capsule rupture occurred without vitreous loss.
      The haptics of the intraocular lens (IOL) were implanted in the ciliary sulcus,
      and the IOL optic was fixated in the capsular bag by the anterior laser
      capsulotomy. The postoperative visual outcome was excellent, and no further
      complications occurred. In cases of posterior capsule rupture, anterior laser
      capsulotomy of an appropriate size, position, and circularity facilitates secure
      positioning of the IOL. FINANCIAL DISCLOSURE: Dr. Dick is a consultant to Abbott
      Medical Optics, Inc. Dr. Schultz has no financial or proprietary interest in any
      material or method mentioned.

PMID- 26210051
TI  - Adhesion study of cultured human lens capsule cells on hydrophilic intraocular
      lenses coated with polyethylene glycol.
AB  - PURPOSE: To evaluate the adhesion of human lens capsule cells on hydrophilic
      acrylic intraocular lenses (IOLs) coated with polyethylene glycol (PEG). SETTING:
      Department of Ophthalmology, Faculty of Medicine, Universidade Estadual Paulista
      Botucatu, Sao Paulo, Brazil. DESIGN: Experimental study. METHODS: Human anterior
      lens capsules obtained during cataract surgery were cultured and seeded (200
      cells/IOLs) in triplicates on the surface of a copolymer comprising hydroxyethyl
      methacrylate, ethyl methacrylate, and methyl methacrylate IOLs (Loflex) treated
      or not treated with PEG. After 26 hours, the number of viable adherent cells was
      estimated by counting in a hemocytometer. RESULTS: The coating of hydrophilic
      acrylic IOLs with PEG was effective in inhibiting cell adhesion (P < .05). Cells
      showing 2 distinct morphologic patterns-epithelial and dendritic-like-were
      observed during the in vitro establishment of the cultures. A tendency toward
      greater adhesion of dendritic-like cells was observed in untreated IOLs compared
      with treated IOLs (P = .095). CONCLUSION: Coating hydrophilic acrylic IOLs with
      PEG was effective in inhibiting cell adhesion. This treatment might play a role
      in posterior capsule opacification prevention. FINANCIAL DISCLOSURE: No author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 26210052
TI  - Possible risk factors and clinical effects of an opaque bubble layer created with
      femtosecond laser-assisted laser in situ keratomileusis.
AB  - PURPOSE: To report the risk factors and clinical effects of an opaque bubble
      layer (OBL) during creation of a laser in situ keratomileusis (LASIK) flap with
      the Visumax 500 kHz femtosecond laser. SETTING: HanGil Eye Hospital, Incheon,
      South Korea. DESIGN: Retrospective comparative study. METHODS: Visual acuity,
      manifest refraction, intraocular pressure, corneal curvature, corneal thickness,
      and optical quality were evaluated. To prove a previous hypothesis that the
      harder a surgeon applanates during flap creation (hard-docking technique), the
      higher the incidence of OBL, the area of the meniscus on the cornea to which
      pressure was applied by the patient interface was calculated. Eyes were separated
      into 2 groups; that is, OBL-occurrence group and OBL-free group. Clinical
      outcomes in the 2 groups were compared to measure the risk factors and clinical
      effects of an OBL. RESULTS: The study included 827 myopic eyes. The incidence of
      OBL was 5.0% (41 eyes). The mean flat keratometry was steeper and the
      preoperative cornea thicker in the OBL-occurrence group. The OBL-occurrence group
      had harder applanation (ie, a larger area of meniscus) than the OBL-free group.
      The incidence of OBL was higher in the hard-docking technique. Clinical outcomes,
      including refractive error, visual acuity, and optical quality, in the 2 groups
      were not statistically significantly different 1 month after LASIK. CONCLUSIONS:
      The incidence of OBL was 5.0%. A steep, thick cornea and a hard-docking technique
      could be risk factors for an OBL. The OBL did not appear to affect optical
      quality or visual outcomes. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 26210053
TI  - Posterior capsule opacification in pediatric eyes with and without traumatic
      cataract.
AB  - PURPOSE: To compare the rate of visually significant posterior capsule
      opacification (PCO) in pediatric eyes with and without traumatic cataract.
      SETTING: Storm Eye Institute, Charleston, South Carolina, USA. DESIGN:
      Retrospective case control study. METHODS: Eyes operated on for traumatic
      cataract and having in-the-bag single-piece hydrophobic intraocular lens (IOL)
      implantation were identified. The control group of eyes operated on for
      nontraumatic cataract was matched with reference to age, management of the
      posterior capsule, type of IOL, and follow-up duration. RESULTS: Data from 58
      eyes were studied. Age at surgery was comparable between the study group and the
      control group (7.3 versus 7.8 years) (P = .7). The rate of PCO was statistically
      significantly different between the 2 groups (12/29 eyes versus 2/29 eyes) (P =
      .002). This difference was more marked for those with intact posterior capsules
      (9/12 eyes [75%] and 1/12 eyes [8%] (P = .001) compared with eyes with primary
      posterior capsulectomy and vitrectomy (3/17 [18%] and 1/17 [6%] (P = .6). For
      eyes with intact posterior capsules, the duration between cataract surgery and
      intervention for PCO was 4 to 15 months in the traumatic cataract group; 1 eye in
      the nontraumatic cataract group required intervention 20 months after surgery.
      CONCLUSIONS: Eyes with traumatic cataract were more likely to develop PCO than
      eyes without traumatic cataract. The results also suggest that PCO develops
      faster in eyes with traumatic cataract. Primary posterior capsulectomy and
      vitrectomy should be considered for children having traumatic cataract surgery,
      irrespective of age at the time of surgery. FINANCIAL DISCLOSURE: Neither author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 26210054
TI  - Idiopathic stromal keratitis resembling central toxic keratopathy.
AB  - A 28-year-old previously emmetropic woman presented with a 2-day history of
      bilateral photophobia and blurred vision. She had no history of corneal surgery
      or contact lens use. Snellen uncorrected distance visual acuity (UDVA) was 6/12
      bilaterally. Bilateral anterior stromal infiltration of the central cornea was
      seen, with no overlying epithelial defect and intact sensation. There was a
      marked hyperopic shift, central corneal thinning, and associated keratometric
      flattening. The patient was started on topical corticosteroids. Over 12 weeks,
      the UDVA returned to 6/5 with emmetropization of the refractive status and
      thickening of the central cornea. The clinical findings in our patient resemble
      those of central toxic keratopathy (CTK) in post-refractive-surgery cases,
      suggesting a similar mechanism. To our knowledge, this is the first report of a
      patient presenting with a CTK-like syndrome in the absence of previous
      keratorefractive surgery or contact lens use. The pathophysiology of this
      condition remains elusive and requires further investigation. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 26210055
TI  - Publication bias and small-study effects magnified effectiveness of
      antipsychotics but their relative ranking remained invariant.
AB  - OBJECTIVES: Publication bias (PB) may seriously compromise inferences from meta
      analyses. The aim of this article was to assess the potential effect of small
      study effects and PB on the recently estimated relative effectiveness and ranking
      of pharmacological treatments for schizophrenia. STUDY DESIGN AND SETTING: We
      used a recently published network of 167 trials involving 36,871 patients and
      comparing the effectiveness of 15 antipsychotics and placebo. We used novel
      visual and statistical methods to explore if smaller trials are associated with
      larger treatment effects and a selection model to explore if the probability of
      trial publication is associated with the magnitude of effect. We conducted a
      network meta-analysis of the published evidence as our primary analysis and used
      a sensitivity analysis considering low, moderate, and severe selection bias (that
      corresponds to the number of unpublished trials) with an aim to evaluate
      robustness of point estimates and ranking. We explored whether placebo-controlled
      and head-to-head trials are associated with different levels of PB. RESULTS: We
      found that small placebo-controlled trials exaggerated slightly the efficacy of
      antipsychotics, and PB was not unlikely in the evidence based on placebo
      controlled trials; however, ranking of antipsychotics remained robust.
      CONCLUSION: The total evidence comprises many head-to-head trials that do not
      appear to be prone to small-study effects or PB, and indirect evidence appears to
      "wash out" some of the biases in the placebo-controlled trials.

PMID- 26210056
TI  - Arabic cross cultural adaptation and validation of the National Institutes of
      Health Stroke Scale.
AB  - INTRODUCTION: The National Institutes of Health Stroke Scale (NIHSS), the most
      commonly used tool to quantify neurological deficit in acute stroke, was
      initially developed in English. We present our experience in developing and
      validating an Arabic version of the NIHSS (arNIHSS). METHODS:  RESULTS: In
      6months, 137 patients were recruited (mean age+/-standard deviation 62+/-12years;
      48 women). For interrater agreement, weighted kappa value ranged from 0.36 to
      0.66 and intraclass correlation coefficient (ICC) for the whole scale was
      excellent at 0.95 (95% confidence interval [CI] 0.94-0.97). For intrarater
      agreement, weighted kappa ranged from 0.52 to 1.0 and the ICC was 0.94 (95% CI
      0.87-0.98). The construct validity of the arNIHSS is demonstrated by its
      correlation with the DWI-ASPECT and the 3months mRS score (Spearman correlation 
      0.46 and 0.58 respectively; P<0.001 for both). CONCLUSION: We developed and
      validated a culturally adapted Arabic version of the NIHSS. Further validation in
      other Arab countries is recommended.

PMID- 26210057
TI  - Statistical and Methodological Considerations for the Interpretation of
      Intranasal Oxytocin Studies.
AB  - Over the last decade, oxytocin (OT) has received focus in numerous studies
      associating intranasal administration of this peptide with various aspects of
      human social behavior. These studies in humans are inspired by animal research,
      especially in rodents, showing that central manipulations of the OT system affect
      behavioral phenotypes related to social cognition, including parental behavior,
      social bonding, and individual recognition. Taken together, these studies in
      humans appear to provide compelling, but sometimes bewildering, evidence for the
      role of OT in influencing a vast array of complex social cognitive processes in
      humans. In this article, we investigate to what extent the human intranasal OT
      literature lends support to the hypothesis that intranasal OT consistently
      influences a wide spectrum of social behavior in humans. We do this by
      considering statistical features of studies within this field, including factors
      like statistical power, prestudy odds, and bias. Our conclusion is that
      intranasal OT studies are generally underpowered and that there is a high
      probability that most of the published intranasal OT findings do not represent
      true effects. Thus, the remarkable reports that intranasal OT influences a large
      number of human social behaviors should be viewed with healthy skepticism, and we
      make recommendations to improve the reliability of human OT studies in the
      future. 

PMID- 26210058
TI  - Frontal Cortex Stimulation Reduces Vigilance to Threat: Implications for the
      Treatment of Depression and Anxiety.
AB  - BACKGROUND: The difficulty in treating mood disorders has brought about clinical
      interest in alternative treatments, such as transcranial direct current
      stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC). However, the
      optimal parameters for stimulation and underlying mechanisms of action are
      unclear. Psychiatric treatments have acute effects on emotional processing that
      predict later therapeutic action. Such effects have been proposed as cognitive
      biomarkers for screening novel treatments for depression and anxiety. METHODS:
      This study assessed the effect of tDCS on a battery of emotional processing
      measures sensitive to antidepressant action. To refine optimal stimulation
      parameters, DLPFC stimulation using two common electrode montages was compared
      with sham. Sixty healthy volunteers received 20 minutes of active or sham DLPFC
      stimulation before completing computerized emotional processing tasks, including
      a dot-probe measure of vigilance to threat. RESULTS: Relative to sham
      stimulation, participants receiving simultaneous anodal stimulation of left DLPFC
      and cathodal stimulation of right DLPFC (bipolar-balanced montage) showed reduced
      vigilance to threatening stimuli. There was no such significant effect when the
      cathode was placed on the supraorbital ridge (bipolar-unbalanced montage). There
      were no effects of tDCS on other measures of emotional processing. CONCLUSIONS:
      Our findings provide the first experimental evidence that modulating activity in
      the DLPFC reduces vigilance to threatening stimuli. This significant reduction in
      fear vigilance is similar to that seen with anxiolytic treatments in the same
      cognitive paradigm. The finding that DLPFC tDCS acutely alters the processing of
      threatening information suggests a potential cognitive mechanism that could
      underwrite treatment effects in clinical populations.

PMID- 26210059
TI  - Innovative Treatment Based on Historical Roots.

PMID- 26210061
TI  - Affective changes during the postpartum period: Influences of genetic and
      experiential factors.
AB  - This article is part of a Special Issue "Parental Care". The postpartum period
      involves some truly transformational changes in females' socioemotional
      behaviors. For most female laboratory rodents and women, these changes include an
      improvement in their affective state, which has positive consequences for their
      ability to sensitively care for their offspring. There is heterogeneity among
      females in the likelihood of this positive affective change, though, and some
      women experience elevated anxiety or depression (or in rodents anxiety- or
      depression-related behaviors) after giving birth. We aim to contribute to the
      understanding of this heterogeneity in maternal affectivity by reviewing selected
      components of the scientific literatures on laboratory rodents and humans
      examining how mothers' physical contact with her infants, genetics, history of
      anxiety and depression and early-life and recent-life experiences contribute to
      individual differences in postpartum affective states. These studies together
      indicate that multiple biological and environmental factors beyond female
      maternal state shape affective responses during the postpartum period, and
      probably do so in an interactive manner. Furthermore, the similar capacity of
      some of these factors to modulate anxiety and depression in human and rodent
      mothers suggests cross-species conservation of mechanisms regulating postpartum
      affectivity. 

PMID- 26210062
TI  - RU486 facilitates or disrupts the sensitization of sexual behaviors by estradiol
      in the ovariectomized Long-Evans rat: Effect of timecourse.
AB  - An acute injection of estradiol benzoate (EB) to the ovariectomized (OVX) rat
      activates low levels of lordosis, and subsequent progesterone (P) administration
      augments lordosis and recruits a complete pattern of sexual behavior including
      appetitive behaviors (e.g., hops/darts and solicitations). However, repeated
      injections of 5MUg or 10MUg EB (but not 2MUg EB), administered every 4days to
      sexually-experienced OVX rats results in a behavioral sensitization, such that
      lordosis quotients (LQs) and appetitive behaviors progressively increase. We have
      shown that adrenal P does not play a critical role because behavioral
      sensitization to EB is not prevented by adrenalectomy. Here we tested whether P
      receptors play a role by examining the effect of chronic administration of the P
      receptor antagonist RU486 at a dose that reliably inhibits sexual behavior in
      fully primed OVX rats. Females were treated with EB (5 or 10MUg), and 5mg RU486
      dissolved in 0.4mL vehicle (VEH; 80% sesame oil, 15% benzyl benzoate, 5% benzyl
      alcohol) 48h and 5h prior to each of 7 tests, respectively, occurring at 4-day
      intervals in unilevel 4-hole pacing chambers. Control animals were treated with
      2, 5, or 10MUg EB+VEH. As expected, sensitization did not occur in females
      treated with 2MUg EB+VEH, and those females received fewer intromissions and
      ejaculations than all other groups. RU486 did not prevent the sensitization of
      LQ, moderate and high lordosis magnitudes (LM2 and LM3) or appetitive sexual
      behaviors on early tests, and in fact potentiated appetitive behaviors, LQ, LM2
      and LM3, consistent with its facilitative actions in females treated with EB
      alone, as we and others have reported previously. However, despite the initial
      facilitation, blocking P receptors by chronic administration of RU486 inhibited
      the maintenance of behavioral sensitization to EB. 

PMID- 26210060
TI  - The Role of Endocannabinoid Signaling in Cortical Inhibitory Neuron Dysfunction
      in Schizophrenia.
AB  - Cannabis use has been reported to increase the risk of developing schizophrenia
      and to worsen symptoms of the illness. Both of these outcomes might be
      attributable to the disruption by cannabis of the endogenous cannabinoid system's
      spatiotemporal regulation of the inhibitory circuitry in the prefrontal cortex
      that is essential for core cognitive processes, such as working memory, which are
      impaired in schizophrenia. In the healthy brain, the endocannabinoid 2
      arachidonylglycerol 1) is synthesized by diacylglycerol lipase in pyramidal
      neurons; 2) travels retrogradely to nearby inhibitory axon terminals that express
      the primary type 1 cannabinoid receptor (CB1R); 3) binds to CB1R, which inhibits
      gamma-aminobutyric acid release from the cholecystokinin-containing population of
      interneurons; and 4) is metabolized by either monoglyceride lipase, which is
      located in the inhibitory axon terminal, or by alpha-beta-hydrolase domain 6,
      which is co-localized presynaptically with diacylglycerol lipase. Investigations
      of the endogenous cannabinoid system in the prefrontal cortex of subjects with
      schizophrenia have found evidence of higher metabolism of 2-arachidonylglycerol,
      as well as both greater CB1R receptor binding and lower levels of CB1R messenger
      RNA and protein. Current views on the potential pathogenesis of these
      alterations, including disturbances in the development of the endogenous
      cannabinoid system, are discussed. In addition, how interactions between these
      alterations in the endocannabinoid system and those in other inhibitory neurons
      in the prefrontal cortex in subjects with schizophrenia might increase the
      liability to adverse outcomes with cannabis use is considered. 

PMID- 26210064
TI  - Drug-induced status epilepticus.
AB  - Drug-induced status epilepticus (SE) is a relatively uncommon phenomenon,
      probably accounting for less than 5% of all SE cases, although limitations in
      case ascertainment and establishing causation substantially weaken
      epidemiological estimates. Some antiepileptic drugs, particularly those with
      sodium channel or GABA(gamma-aminobutyric acid)-ergic properties, frequently
      exacerbate seizures and may lead to SE if used inadvertently in generalized
      epilepsies or less frequently in other epilepsies. Tiagabine seems to have a
      particular propensity for triggering nonconvulsive SE sometimes in patients with
      no prior history of seizures. In therapeutic practice, SE is most commonly seen
      in association with antibiotics (cephalosporins, quinolones, and some others) and
      immunotherapies/chemotherapies, the latter often in the context of a reversible
      encephalopathy syndrome. Status epilepticus following accidental or intentional
      overdoses, particularly of antidepressants or other psychotropic medications, has
      also featured prominently in the literature: whilst there are sometimes fatal
      consequences, this is more commonly because of cardiorespiratory or metabolic
      complications than as a result of seizure activity. A high index of suspicion is
      required in identifying those at risk and in recognizing potential clues from the
      presentation, but even with a careful analysis of patient and drug factors,
      establishing causation can be difficult. In addition to eliminating the potential
      trigger, management should be as for SE in any other circumstances, with the
      exception that phenobarbitone is recommended as a second-line treatment for
      suspected toxicity-related SE where the risk of cardiovascular complications is
      higher anyways and may be exacerbated by phenytoin. There are also specific
      recommendations/antidotes in some situations. The outcome of drug-induced status
      epilepticus is mostly good when promptly identified and treated, though less so
      in the context of overdoses. This article is part of a Special Issue entitled
      "Status Epilepticus". 

PMID- 26210063
TI  - Clinical outcome of generalized periodic epileptiform discharges on first EEG in
      patients with hypoxic encephalopathy postcardiac arrest.
AB  - INTRODUCTION: The EEG, alongside clinical examination, imaging studies, and
      SSEPs, is used to determine the prognosis following hypoxic encephalopathy
      postcardiac arrest. Generalized periodic epileptiform discharges (GPEDs) are
      recognized as a "malignant" EEG pattern associated with very poor outcome with
      previous studies reporting no or few survivors. We looked at our database of
      cardiac arrest patients who subsequently developed GPEDs to determine clinical
      outcome and profile any survivors. METHODOLOGY: We identified all cardiac arrest
      patients treated at King's College Hospital between 2011-2014 who developed
      hypoxic encephalopathy associated with GPEDs, BiPLEDs (bilateral periodic
      lateralized epileptiform discharges), and periodic discharges on first EEG. We
      collected clinical data including age, gender, downtime, EEG reactivity, presence
      of seizures or myoclonus, and outcome. Survivors were defined as patients who
      were discharged from the hospital to home or a neurorehabilitation unit. RESULTS:
      Thirty-six postcardiac arrest patients with hypoxic encephalopathy were
      identified, 24/36 with GPEDs, and 12/36 with BiPLEDs on first EEG. The mean age
      of patients was 62.8 +/- 14.5 years old, with 27 males (75%) and 9 females (25%).
      Ten of thirty-six patients survived, which is slightly higher than previously
      reported. Statistical tests to compare clinical characteristics between survivors
      and nonsurvivors demonstrated no significant differences except for trend to
      significance for the presence of reactivity on first EEG (p = 0.0794). On
      discharge, one survivor had good functional outcome (and subsequently became
      independent), but all others were dependent for all ADLs (activities of daily
      living). CONCLUSION: Generalized periodic epileptiform discharges carry a grave
      clinical prognosis following cardiac arrest. This study did identify a higher
      number of survivors compared to previous studies, but most were severely disabled
      at hospital discharge. Reactivity of the first EEG might predict better prognosis
      and merit further evaluation. This article is part of a Special Issue entitled
      "Status Epilepticus".

PMID- 26210065
TI  - Ergosterol peroxide from Chaga mushroom (Inonotus obliquus) exhibits anti-cancer
      activity by down-regulation of the beta-catenin pathway in colorectal cancer.
AB  - AIM OF THE STUDY: In this study, we examined the effect of different fractions
      and components of Chaga mushroom (Inonotus Obliquus) on viability and apoptosis
      of colon cancer cells. Among them, one component showed the most effective growth
      inhibition and was identified as ergosterol peroxide by NMR analysis. We
      investigated the anti-proliferative and apoptosis mechanisms of ergosterol
      peroxide associated with its anti-cancer activities in human colorectal cancer
      (CRC) cell lines and tested its anti-tumor effect on colitis-induced CRC
      developed by Azoxymethane (AOM)/Dextran sulfate sodium (DSS) in a mouse model.
      MATERIALS AND METHODS: We used MTT (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide) assays, flow cytometry assays, Western blot
      analysis, colony formation assays, reverse transcription-polymerase chain
      reaction (RT-PCR), immunohistochemistry (IHC), and AOM/DSS mouse models to study
      the molecular mechanism of metastatic activities in CRC cells. RESULTS:
      Ergosterol peroxide inhibited cell proliferation and also suppressed clonogenic
      colony formation in HCT116, HT-29, SW620 and DLD-1 CRC cell lines. The growth
      inhibition observed in these CRC cell lines was the result of apoptosis, which
      was confirmed by FACS analysis and Western blotting. Ergosterol peroxide
      inhibited the nuclear levels of beta-catenin, which ultimately resulted in
      reduced transcription of c-Myc, cyclin D1, and CDK-8. Ergosterol peroxide
      administration showed a tendency to suppress tumor growth in the colon of AOM/DSS
      treated mice, and quantification of the IHC staining showed a dramatic decrease
      in the Ki67-positive staining and an increase in the TUNEL staining of colonic
      epithelial cells in AOM/DSS-treated mice by ergosterol peroxide for both
      prevention and therapy. CONCLUSION: Our data suggest that ergosterol peroxide
      suppresses the proliferation of CRC cell lines and effectively inhibits colitis
      associated colon cancer in AOM/DSS-treated mice. Ergosterol peroxide down
      regulated beta-catenin signaling, which exerted anti-proliferative and pro
      apoptotic activities in CRC cells. These properties of ergosterol peroxide
      advocate its use as a supplement in colon cancer chemoprevention.

PMID- 26210066
TI  - The adrenergic-regulated CRTC1 and CRTC2 phosphorylation and cellular
      distribution is independent of endogenous SIK1 in the male rat pinealocyte.
AB  - Salt inducible kinase 1 (SIK1) has been reported to repress cAMP-response element
      binding protein (CREB)-mediated gene transcription by causing the nuclear export
      of CREB-regulated transcription coactivators (CRTCs) through phosphorylation.
      Although the repressor role of SIK1 in suppressing the expression of
      arylalkylamine N-acetyltransferase, the enzyme that controls the daily rhythm in
      melatonin production in the rat pineal gland, has been established, whether SIK1
      regulates the phosphorylation and localization of CRTC1 and CRTC2 in this tissue
      remains unclear. The present study found that overexpressing SIK1 in NE
      stimulated rat pinealocytes could increase the phosphorylation of CRTC1 and
      CRTC2, reduced selectively the nuclear level of CRTC2 (but not that of CRTC1),
      and elevated the cytosolic levels of both CRTC1 and CRTC2. In contrast, transient
      knockdown of endogenous SIK1 had no effect on the phosphorylation or distribution
      of CRTC1 and CRTC2 in norepinephrine (NE)-stimulated pinealocytes. Our results
      also showed that adrenergic blockade during NE stimulation led to a rapid
      rephosphorylation and decline in the nucleus levels of CRTC1 and CRTC2; however
      SIK1 knockdown had no effect on this rapid rephosphorylation. Moreover, studies
      with kinase inhibitors revealed that kinase(s) sensitive to KT5823 appeared to be
      involved in this rapid rephosphorylation. Together, these results indicate that
      although overexpressing SIK1 can phosphorylate CRTC1 and CRTC2 in the NE
      stimulated pinealocyte, the endogenous SIK1, in spite of its induction by NE,
      does not appear to be the main regulator of the phosphorylation and intracellular
      localization of these two coactivators. 

PMID- 26210067
TI  - Optical coherence tomography in the assessment of oral squamous cell carcinoma
      resection margins.
AB  - BACKGROUND: Incomplete surgical removal of cancer is believed to be the main
      cause of local recurrence and high mortality. This study assessed the use of
      optical technology (namely optical coherence tomography [OCT]) in examining oral
      squamous cell carcinoma (OSCC) resection margins to assess if this modality could
      guide the surgeon during surgical resections. MATERIALS AND METHODS: Twenty-eight
      T1-T2 N0M0 oral squamous cell carcinoma patients participated in this study.
      Nineteen patients were males and nine were females. The majority of lesions were
      in the ventro-lateral tongue, floor of mouth, retromolar trigone and the buccal
      mucosa. Following tumour resection, the specimen resection margins were optically
      scanned in the immediate ex vivo phase. Two independent assessors commented on
      the four resection margins of each specimen. The findings were then compared to
      the corresponding gold standard histopathology. The average epithelial thickness
      for both tumor-free and tumor-involved margins was also calculated. RESULTS: The
      pathology reports of the 112 margins revealed 90 tumor-free margins and 22 tumor
      involved margins. Examining the data from both senior operating surgeons
      (assessors), the overall sensitivity and specificity was found to be 81.5% and
      87%, respectively. Whilst the positive predictive value was 61.5% and the
      negative predictive value was 95%. OCT accuracy for the first assessor was 88%
      and for the second assessor 84%. The assessors' inter-observer agreement was
      "very good" for superior, inferior and medial margins; while agreement on the
      lateral surgical margin status was "good". Using OCT, the mean epithelial
      thickness at the tumor-free resection margins was 360 MUm; while, it was 567 MUm
      for the tumour-involved margins. CONCLUSION: OCT is a valuable tool in the
      assessment of surgical margins. Tumour-involved margins can be identified by
      architectural changes and increase in epithelial layer thickness on the OCT
      image. Further studies are required to assess tumour margins in vivo.

PMID- 26210068
TI  - Measuring comorbidity in patients receiving dialysis: can we do better?

PMID- 26210070
TI  - Prevalence and patterns of multimorbidity in northeastern China: a cross
      sectional study.
AB  - OBJECTIVES: Information on multimorbidity in the general populations of
      developing countries is lacking. We examine the prevalence and patterns of
      multimorbidity in northeastern China. STUDY DESIGN: A cross-sectional study was
      conducted on adult residents in Jilin Province, northeastern China from June 2012
      to August 2012. METHODS: Data were collected from a large cross-sectional study
      (n = 21,435) of adult community residents in Jilin Province in northeastern
      China. Multimorbidity, or co-morbidity, was defined as having two or more of 18
      specified prevalent chronic diseases. A range of demographics, socio-economic
      factors, other risk factors and general mental health were used in describing the
      distribution of multimorbidity and in exploring the associations between them.
      RESULTS: Almost a quarter (24.7%) of the adults were found to be multimorbid for
      chronic diseases. Multimorbidity was more common among older adults, women, rural
      residents and those with low income. Smoking, increasing BMI and psychological
      distress were independently associated with multimorbidity. Multimorbid patients
      were frequent users of primary care. Most dyads of chronic diseases co-occurred
      more frequently than would be expected on the basis of chance. CONCLUSIONS:
      Researchers, clinicians and policy makers need to pay special attention to the
      health care challenges of multimorbidity and develop effective intervention
      strategies and programs to reduce the burden of multimorbidity.

PMID- 26210069
TI  - Patient-Reported Outcome Instruments for Physical Symptoms Among Patients
      Receiving Maintenance Dialysis: A Systematic Review.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) receiving dialysis have
      poor health-related quality of life. Physical symptoms are highly prevalent among
      dialysis-dependent patients and play important roles in health-related quality of
      life. A range of symptom assessment tools have been used in dialysis-dependent
      patients, but there has been no previous systematic assessment of the existing
      symptom measures' content, validity, and reliability. STUDY DESIGN: Systematic
      review of the literature. SETTINGS & POPULATION: Patients with ESRD on
      maintenance dialysis therapy. SELECTION CRITERIA FOR STUDIES: Instruments with 3
      or more physical symptoms previously used in dialysis-dependent patients and
      evidence of validity or reliability testing. INTERVENTION: Patient-reported
      physical symptom assessment instrument. OUTCOMES: Instrument symptom-related
      content, validity, and reliability. RESULTS: From 3,148 screened abstracts, 89
      full-text articles were eligible for review. After article exclusion and further
      article identification by reference reviews, 58 articles on 23 symptom assessment
      instruments with documented reliability or validity testing were identified. Of
      the assessment instruments, 43.5% were generic and 56.5% were ESRD specific.
      Symptoms most frequently assessed were fatigue, shortness of breath, insomnia,
      nausea and vomiting, and appetite. Instruments varied widely in respondent time
      burden, recall period, and symptom attributes. Few instruments considered recall
      periods less than 2 weeks and few assessed a range of symptom attributes.
      Psychometric testing was completed for congruent validity (70%), known-group
      validity (25%), responsiveness (30%), internal consistency (78%), and test-retest
      reliability (65%). Content validity was assessed in dialysis populations in 57%
      of the 23 instruments. LIMITATIONS: Consideration of physical symptoms only and
      exclusion of single symptom-focused instruments. CONCLUSIONS: The number of
      available instruments focused exclusively on physical symptoms in dialysis
      patients is limited. Few symptom-containing instruments have short recall
      periods, assess diverse symptom attributes, and have undergone comprehensive
      psychometric testing. Improved symptom-focused assessment tools are needed to
      improve symptom evaluation and symptom responsiveness to intervention among
      dialysis-dependent patients.

PMID- 26210072
TI  - Governance for health - grasping at the levers of glocal health.

PMID- 26210071
TI  - Pregnancy and internet: sociodemographic and geographic differences in e-health
      practice. Results from an Italian multicenter study.
AB  - OBJECTIVES: Since the new millennium, the number of e-health users has
      significantly increased. Among these, a particular category of people who are
      interested by this phenomenon is the one of pregnant women. The aim of the
      present study is to assess the sociodemographic and geographic differences
      existing in a sample of Italian pregnant women who search for information on the
      web. STUDY DESIGN: Multicenter cross-sectional survey. METHODS: The present study
      has been conducted from November 2011 to September 2012, in seven Italian cities,
      located in the North, in the Centre and in the South of Italy. Data were
      collected through an anonymous questionnaire, administered in waiting rooms of
      outpatient departments by trained medical doctors. Data were analysed through
      multivariate logistic regression models. RESULTS: Overall, 1347 responders were
      interviewed. Eighty-six percent of them declared to surf the internet to retrieve
      pregnancy-related information. The most searched topics were fetal development
      (51.3%), healthy lifestyle during pregnancy (48.7%), physiology of pregnancy
      (39.8%), generic and specific tips/advices during pregnancy (37.2%) and lactation
      (36.8%). Statistically significant differences (P < 0.05) according to geographic
      origin, age and educational level were found with regard to the most frequently
      searched information on the Web, the reasons that pushed pregnant women to
      practice e-health, and the possibility to change lifestyles after e-health.
      CONCLUSIONS: Our findings suggest that the phenomenon of pregnancy e-health is
      widespread and show social and geographic differences, in particular about city
      of residence, age and educational level. It might encourage healthcare
      professionals to be more available and exhaustive during routine visits and to be
      more careful about web content on this topic, also addressing the different needs
      into different geographic contexts.

PMID- 26210073
TI  - Prescribing Patterns of Intravenous Golimumab for Rheumatoid Arthritis.
AB  - PURPOSE: The use of intravenous golimumab (GLM-IV), in combination with
      methotrexate, was approved by the US Food and Drug Administration in July 2013
      for the treatment of moderate to severe, active rheumatoid arthritis (RA). GLM-IV
      is available in 50-mg vials, and the prescribing information specifies a dosing
      regimen of 2 mg/kg at 0 and 4 weeks and then every 8 weeks thereafter. The
      purpose of this study was to examine the patterns of prescribing and
      administration of GLM-IV, including the demographic, clinical, and utilization
      characteristics of patients with RA newly treated with GLM-IV. METHODS:
      Rheumatology practices across the continental United States were solicited for a
      chart-review study. Inclusion criteria were: (1) diagnosis of RA; (2) current
      treatment with GLM-IV; (3) age >=18 years; and (4) lack of pregnancy (in female
      patients). Physicians were offered a monetary incentive for each eligible chart
      provided. An electronic case-report form was developed to aid in the chart data
      extraction and included fields for demographic characteristics, available
      comorbid diagnoses, prior RA treatments, and doses and dates of GLM-IV
      administration. FINDINGS: A total of 117 eligible patient charts from 15
      rheumatologist practices were reviewed. The patient sample was predominantly
      female (81.2%), with a mean (SD) age of 55.4 (14.5) years. A total of 55.6% of
      patients had evidence of biologic treatment before receiving GLM-IV, and 53% had
      at least 1 comorbid condition. In total, 300 individual GLM-IV infusions from
      this sample were reviewed. Due to the relatively recent approval of GLM-IV use by
      the US Food and Drug Administration, the majority of patients in this sample
      (69.2%) had received only between 2 and 4 infusions at the time of the review.
      For infusion records with valid dose data, the mean number of administered vials
      was 3.6 (0.8) (total dose, 180 mg); the majority of patients received a dose
      consistent with the prescribed dose of 2 mg/kg. Combination therapy with
      methotrexate was observed in the charts of a minority of patients (27.4%). The
      mean interval between induction and the first follow-up infusion was 32.9 (11.4)
      days, with a mean maintenance interval of 56.5 (13.3) days. IMPLICATIONS: This
      analysis provides an early glimpse of the patterns of prescribing GLM-IV.
      Overall, patients appeared to have been receiving GLM-IV in accordance with Food
      and Drug Administration labeling; although the rate of prescribing methotrexate
      was low, dosages and administration intervals were within the expected ranges.

PMID- 26210074
TI  - Cost of Bleeding in Trauma and Complex Cardiac Surgery.
AB  - PURPOSE: Trauma and complex cardiac surgery are associated with a high risk of
      bleeding complications. The difference in costs between patients who require
      bleeding control measures and those who do not is poorly understood. Our goal was
      to assess the cost of care and outcomes for patients in these settings. METHODS:
      Patients >18 years of age, who were discharged between January 2010 and December
      2012, were retrospectively identified in the Premier Hospital Database based on
      International Classification of Disease, Ninth Revision codes. These patients
      were categorized as having received blood products ("bleeding patients") or not
      ("nonbleeding patients"). Patients with costs and length of stay (LOS) of zero
      were excluded. Differences in treatment costs and outcomes were assessed using
      univariate analysis and multivariate modeling. FINDINGS: Bleeding trauma patients
      (n = 8800) had a 150% higher total cost of care (P < 0.001; 146% after excluding
      costs of agents used for bleeding control, P < 0.001), an 81.3% longer hospital
      LOS (P < 0.001), and a 65.2% longer intensive care unit (ICU) LOS (P < 0.001)
      than nonbleeding patients (n = 53,727). Bleeding complex cardiac surgery patients
      (n = 82,832) had a 133.2% higher total cost of care (P < 0.001; 128.7% after
      excluding costs of agents used for bleeding control, P < 0.001), a 155.6% longer
      hospital LOS (P < 0.001), and an 89.3% longer ICU LOS (P < 0.001) than
      nonbleeding patients (n = 380,902). IMPLICATIONS: Trauma and cardiac surgery
      patients who experienced bleeding and received allogeneic blood product
      transfusions had significantly worse outcomes, including longer LOS, greater
      inpatient mortality, and higher costs of care (even when excluding costs of
      agents used for bleeding control) than those who did not.

PMID- 26210075
TI  - Persistent human Borna disease virus infection modifies the acetylome of human
      oligodendroglia cells towards higher energy and transporter levels.
AB  - BACKGROUND: Borna disease virus (BDV) is a neurotropic RNA virus persistently
      infecting mammalian hosts including humans. Lysine acetylation (Kac) is a key
      protein post-translational modification (PTM). The unexpectedly broad regulatory
      scope of Kac let us to profile the entire acetylome upon BDV infection. METHODS:
      The acetylome was profiled through stable isotope labeling for cell culture
      (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated
      using bioinformatics. RESULTS: We identified and quantified 791 Kac sites in 473
      Kac proteins in human BDV Hu-H1-infected and non-infected oligodendroglial (OL)
      cells. Bioinformatic analysis revealed that BDV infection alters the acetylation
      of metabolic proteins, membrane-associated proteins and transmembrane transporter
      activity, and affects the acetylation of several lysine acetyltransferases (KAT).
      CONCLUSIONS: Upon BDV persistence the OL acetylome is manipulated towards higher
      energy and transporter levels necessary for shuttling BDV proteins to and from
      nuclear replication sites.

PMID- 26210077
TI  - The conundrum of a unique protein encoded by citrus tristeza virus that is
      dispensable for infection of most hosts yet shows characteristics of a viral
      movement protein.
AB  - Citrus tristeza virus (CTV), one of the most economically important viruses,
      produces a unique protein, p33, which is encoded only in the genomes of isolates
      of CTV. Recently, we demonstrated that membrane association of the p33 protein
      confers virus ability to extend its host range. In this work we show that p33
      shares characteristics of viral movement proteins. Upon expression in a host
      cell, the protein localizes to plasmodesmata and displays the ability to form
      extracellular tubules. Furthermore, p33 appears to traffic via the cellular
      secretory pathway and the actin network to plasmodesmata locations and is likely
      being recycled through the endocytic pathway. Finally, our study reveals that p33
      colocalizes with a putative movement protein of CTV, the p6 protein. These
      results suggest a potential role of p33 as a noncanonical viral movement protein,
      which mediates virus translocation in the specific hosts. 

PMID- 26210076
TI  - Genotype-specific variation in West Nile virus dispersal in California.
AB  - West Nile virus (WNV) is an arbovirus that was first reported in North America in
      New York in 1999 and, by 2003, had spread more than 4000 km to California.
      However, variation in viral genetics associated with spread is not well
      understood. Herein, we report sequences for more than 100 WNV isolates made from
      mosquito pools that were collected from 2003 to 2011 as part of routine
      surveillance by the California Mosquito-borne Virus Surveillance System. We
      performed phylogeographic analyses and demonstrated that 5 independent
      introductions of WNV (1 WN02 genotype strain and 4 SW03 genotype strains)
      occurred in California. The SW03 genotype of WNV was constrained to the
      southwestern U.S. and had a more rapid rate of spread. In addition, geographic
      constraint of WNV strains within a single region for up to 6 years suggest viral
      maintenance has been driven by resident, rather than migratory, birds and
      overwintering in mosquitoes.

PMID- 26210078
TI  - Stroke me for longer this touch feels too short: The effect of pleasant touch on
      temporal perception.
AB  - Negative, painful, somatosensory stimulation lengthens the perceived duration of
      time. However, to date, no research has explored the influence of positive,
      pleasant, somatosensory stimulation on temporal perception. Here we asked whether
      gentle stroking touch influences perceptions of duration. Pleasant (gentle) and
      mildly unpleasant (rough) tactile stimulation was delivered whilst participants
      estimated the duration of a neutral visual stimulus. Pleasant touch resulted in
      shorter estimates of duration than unpleasant touch. There was no difference in
      duration perception in the unpleasant and control conditions. Taken together with
      the results of previous research (Ogden, Moore, Redfern, & McGlone, 2015), the
      results of this study suggest that pleasant and painful somatosensory stimulation
      have opposing effects on temporal perception, and additionally that pleasant
      touch can alter aspects of perceptual and attentional processing outside the
      purely affective domain. 

PMID- 26210079
TI  - Fully Threaded Versus Partially Threaded Screws: Determining Shear in Cancellous
      Bone Fixation.
AB  - Many researchers have studied and compared various forms of intraosseous
      fixation. No studies have examined the effects of shear through stiffness and
      failure strength of a fully threaded versus a partially threaded screw. Our
      hypothesis was that the fully threaded lag screw technique would provide greater
      shear strength and resistance. Thirty-six synthetic sawbone blocks were used to
      test screw fixation. In group 1 (n = 9), 2 blocks were fixed together using a
      fully threaded 4.0-mm stainless steel cancellous bone screw and the lag
      technique. In group 2 (n = 8), 2 blocks were fixed together using the standard
      manufacturer-recommended method for inserting 4.0-mm partially threaded stainless
      steel cancellous bone screws. The constructs were then mechanically tested. Shear
      was applied by compressing each construct at an axial displacement rate of 0.5
      mm/s until failure. The fully threaded screw had a significantly greater (p =
      .026) initial stiffness (106.4 +/- 15.8 N/mm) than the partially threaded screw
      (80.1 +/- 27.5 N/mm). The yield load and displacement for the fully threaded
      group (429.4 +/- 11.7 N and 7.2 +/- 0.35 mm) were 64% and 67% greater than those
      for the partially threaded screw group (261.4 +/- 26.1 N and 4.3 +/- 1.03 mm),
      respectively. The results of the present study have demonstrated the importance
      of a full-thread construct to prevent shear and to decrease strain at the
      fracture. The confirmation of our hypothesis questions the future need and use of
      partially threaded screws for cancellous bone fixation. 

PMID- 26210080
TI  - Minimally Invasive Calcaneal Osteotomy: Does the Shannon Burr Endanger the
      Neurovascular Structures? A Cadaveric Study.
AB  - Calcaneal osteotomies are used to correct hindfoot alignment. Traditional open
      procedures have been plagued with complications. Various minimally invasive
      techniques have been described but are laborious and time-consuming. A
      percutaneous technique using a side cutting "Shannon" burr offers a simple and
      reliable alternative; however, little evidence is available to address the safety
      concerns. The aim of the present study was to quantify the risk posed to the
      medial and lateral neurovascular structures using this technique. The study was
      performed at the anatomy department, University of Sussex, using 13 fresh-frozen,
      below-the-knee cadaveric specimens during a training session held by WG
      Healthcare UK, Ltd. (Letchworth, Herts). The participants were 11 consultant
      orthopedic surgeons, who were inexperienced in minimally invasive surgery, and 2
      demonstrators. Each performed a chevron calcaneal osteotomy using a Shannon burr
      by way of a lateral percutaneous approach under fluoroscopic guidance. The
      authors subsequently dissected the specimens to identify the neurovascular
      structures, describe their anatomic relations and proximity to the burr, and note
      any damage incurred. No evidence was found of significant neurovascular injury.
      Two very small proximal branches of the sural nerve were transected, the nerve
      itself passing safely 9 to 21 mm anterosuperior to the entry point. The medial
      neurovascular bundle crossed the path of the osteotomy in 4 specimens but was
      protected by the medial head of the quadratus plantae muscle. In conclusion, the
      Shannon burr for calcaneal osteotomy has the potential to minimize the surgical
      morbidity and maximize surgical efficiency without compromising safety in all
      patients with normal anatomy of the quadratus plantae muscle. 

PMID- 26210081
TI  - Recreational Sports Activities After Calcaneal Fractures and Subsequent Subtalar
      Joint Arthrodesis.
AB  - Subtalar joint arthrodesis is a common treatment for the management of hindfoot
      pathologic entities. Despite pain reduction, hindfoot stiffness is a common
      concern of active patients, who wish to continue or start exercising for fitness.
      The purpose of the present retrospective observational clinical study was to
      assess the rate and type of recreational sports activities in patients before and
      after subtalar joint arthrodesis and to correlate the clinical outcome and the
      level of sports activities. In 33 patients (22 males, 11 females) treated with
      subtalar joint arthrodesis, the pre- and postoperative participation in sports
      and recreational activities was evaluated. The American Orthopaedic Foot and
      Ankle Society hindfoot scale score, 36-item Short Form Health Survey, and a
      visual analog scale for pain were used as clinical outcome measures. The weekly
      session number, session time, and interval to activity recovery after surgery
      were registered. Patients with a subtalar joint arthrodesis returned to a
      satisfactory level of activity postoperatively. The sports participation almost
      reached levels similar to those preoperatively but with a shift from high- to low
      impact activities. 

PMID- 26210082
TI  - Kids Eat Right: Helping Families from Coast to Coast.

PMID- 26210083
TI  - Bring Nutrition Education to Life in the Classroom with MyPlate.

PMID- 26210084
TI  - The Specific Carbohydrate Diet for Inflammatory Bowel Disease: A Case Series.

PMID- 26210086
TI  - In Brief: Achieving a Transparent, Actionable Framework for Public-Private
      Partnerships for Food and Nutrition Research.

PMID- 26210085
TI  - Implementation of Competitive Food and Beverage Standards in a Sample of
      Massachusetts Schools: The NOURISH Study (Nutrition Opportunities to Understand
      Reforms Involving Student Health).
AB  - BACKGROUND: During 2012, Massachusetts adopted comprehensive school competitive
      food and beverage standards that closely align with Institute of Medicine
      recommendations and Smart Snacks in School national standards. OBJECTIVE: We
      examined the extent to which a sample of Massachusetts middle schools and high
      schools sold foods and beverages that were compliant with the state competitive
      food and beverage standards after the first year of implementation, and complied
      with four additional aspects of the regulations. DESIGN: Observational cohort
      study with data collected before implementation (Spring 2012) and 1 year after
      implementation (Spring 2013). PARTICIPANTS/SETTING: School districts (N=37) with
      at least one middle school and one high school participated. MAIN OUTCOME
      MEASURES: Percent of competitive foods and beverages that were compliant with
      Massachusetts standards and compliance with four additional aspects of the
      regulations. Data were collected via school site visits and a foodservice
      director questionnaire. STATISTICAL ANALYSES PERFORMED: Multilevel models were
      used to examine change in food and beverage compliance over time. RESULTS: More
      products were available in high schools than middle schools at both time points.
      The number of competitive beverages and several categories of competitive food
      products sold in the sample of Massachusetts schools decreased following the
      implementation of the standards. Multilevel models demonstrated a 47-percentage
      point increase in food and 46-percentage-point increase in beverage compliance in
      Massachusetts schools from 2012 to 2013. Overall, total compliance was higher for
      beverages than foods. CONCLUSIONS: This study of a group of Massachusetts schools
      demonstrated the feasibility of schools making substantial changes in response to
      requirements for healthier competitive foods, even in the first year of
      implementation.

PMID- 26210087
TI  - A Framework for Public-Private Partnerships in Food and Nutrition Research:
      Implications for Registered Dietitian Nutritionists and the Academy of Nutrition
      and Dietetics.

PMID- 26210088
TI  - Spotlight on Global Malnutrition: A Continuing Challenge in the 21st Century.
AB  - Malnutrition as undernutrition, overnutrition, or an imbalance of specific
      nutrients, can be found in all countries and in both community and hospital
      settings around the world. The prevalence of malnutrition is unacceptably high in
      all settings and affects children, adolescents, pregnant women, and sick and
      older adults. Malnutrition has multiple underlying issues (food insecurity,
      chronic and acute illnesses, sanitation and safety, and aging in the community),
      which need to be addressed. At the same time, direct nutrition interventions
      (food supplements and micronutrient supplementation) help support immediate
      resolution of malnutrition. Awareness of malnutrition issues in the community and
      in clinical setting must be stimulated in order to provide better care. Different
      countries have implemented a wide range of interventions to prevent and treat
      malnutrition. These include nutrition education, engagement of the community,
      resolution of sanitation problems affecting food and water, routine screening and
      assessment and diagnosis of malnutrition (when feasible), and food supplements
      and micronutrients. Such programs are achieving improved outcomes; however,
      further engagement and training is needed for more community and clinical health
      workers. Many countries lack qualified nutrition and dietetics practitioners or
      have low dietitian-to-patient ratios with suboptimal salaries. Thus, an increase
      in number of and empowerment of nutrition and dietetics practitioners is
      desperately needed to help prevent and treat malnutrition globally.

PMID- 26210089
TI  - Where Can I Find Resources for Medical Record Documentation?

PMID- 26210090
TI  - Pathogenic potential of a Costa Rican strain of 'Candidatus Rickettsia
      amblyommii' in guinea pigs (Cavia porcellus) and protective immunity against
      Rickettsia rickettsii.
AB  - 'Candidatus Rickettsia amblyommii' is a spotted fever group rickettsia that is
      not considered pathogenic, although there is serologic evidence of possible
      infection in animals and humans. The aim of this study was to evaluate the
      pathogenic potential of a Costa Rican strain of 'Candidatus R. amblyommii' in
      guinea pigs and determine its capacity to generate protective immunity against a
      subsequent infection with a local strain of Rickettsia rickettsii isolated from a
      human case. Six guinea pigs were inoculated with 'Candidatus R. amblyommii'
      strain 9-CC-3-1 and two controls with cell culture medium. Health status was
      evaluated, and necropsies were executed at days 2, 4, and 13. Blood and tissues
      were processed by PCR to detect the gltA gene, and end titers of anti-'Candidatus
      R. amblyommii' IgG were determined by indirect immunofluorescence. To evaluate
      protective immunity, another 5 guinea pigs were infected with 'Candidatus R.
      amblyommii' (IGPs). After 4 weeks, these 5 IGPs and 3 controls (CGPs) were
      inoculated with pathogenic R. rickettsii. Clinical signs and titers of anti
      Rickettsia IgG were determined. IgG titers reached 1:512 at day 13 post-infection
      with 'Candidatus R. amblyommii'. On day 2 after inoculation, two guinea pigs had
      enlarged testicles and 'Candidatus R. amblyommii' DNA was detected in testicles.
      Histopathology confirmed piogranulomatous orchitis with perivascular inflammatory
      infiltrate in the epididymis. In the protective immunity assay, anti-Rickettsia
      IgG end titers after R. rickettsii infection were lower in IGPs than in CGPs.
      IGPs exhibited only transient fever, while CGP showed signs of severe disease and
      mortality. R. rickettsii was detected in testicles and blood of CGPs. Results
      show that the strain 9-CC-3-1 of 'Candidatus R. amblyommii' was able to generate
      pathology and an antibody response in guinea pigs. Moreover, its capacity to
      generate protective immunity against R. rickettsii may modulate the epidemiology
      and severity of Rocky Mountain spotted fever in areas where both species
      circulate. 

PMID- 26210091
TI  - A case of Francisella tularensis subspecies holarctica in China.
AB  - We report a highly unusual case of ulceroglandular tularemia in Beijing, China.
      The serological texting, and sequencing of three specific genes by PCR analysis,
      suggested that this case was infected by Francisella tularensis. Next, using 15
      canonical single-nucleotide polymorphisms and insertion-deletion markers (SNPs
      INDELs) and five variable-number tandem repeat loci (VNTRs), this case was
      assigned to a known clade from Russia, and not to the four clades that were
      previously identified, including previous Chinese isolates. The case that is
      reported herein provides evidence of type B tularemia in Beijing, and it
      demonstrates unprecedented levels of diversity of the Chinese variant of F.
      tularensis. 

PMID- 26210092
TI  - Comparison of right and left ventricular function and size in Duchenne muscular
      dystrophy.
AB  - INTRODUCTION: Right ventricular (RV) size and function in Duchenne muscular
      dystrophy (DMD) have not been well described. Using cardiac magnetic resonance
      (CMR) imaging we describe the relationship of RV and left ventricular (LV) size
      and function in a large DMD cohort. METHODS: Latest CMR scans of 272 patients
      consecutively seen at a single tertiary referral center (2011-2014) with skeletal
      muscle biopsy confirmed DMD were included. 1.5 and 3 Tesla CMR scanners were
      used. Biventricular ejection fraction (EF), end-diastolic volume index (EDVI),
      mass and mass index were compared across categories of LVEF. RESULTS: Mean age
      was 13.5 +/- 4.9 years. 71% had normal (>= 55%) LVEF while mild (EF 45-54%),
      moderate (EF 30-44%), and severe LV dysfunction (EF <30%) was present in 20%, 6%
      and 3% respectively. The correlation between RVEF and LVEF was weak. Even in
      patients with severe LV dysfunction, RVEF (49.7% +/- 12.9%) was relatively
      preserved. There were no significant differences in RVEDVI and RV mass index
      across categories of LV function. CONCLUSION: In a large DMD cohort, RVEF was
      relatively preserved and RV size was preserved across categories of LV
      dysfunction.

PMID- 26210093
TI  - Iterative reconstruction in single source dual-energy CT pulmonary angiography:
      Is it sufficient to achieve a radiation dose as low as state-of-the-art single
      energy CTPA?
AB  - OBJECTIVE: Dual-energy (DE) brings numerous significant improvements in pulmonary
      CT angiography (CTPA), but is associated with a 15-50% increase in radiation dose
      that prevents its widespread use. We hypothesize that thanks to iterative
      reconstruction (IR), single source DE-CTPA acquired at the same radiation dose
      that a single-energy examination will maintain an equivalent quantitative and
      qualitative image quality, allowing a more extensive use of the DE technique in
      the clinical routine. MATERIAL AND METHODS: Fifty patients (58% men, mean age
      64.8yo +/- 16.2, mean BMI 25.6 +/- 4.5) were prospectively included and underwent
      single source DE-CTPA with acquisition parameters (275 mA fixed tube current, 50%
      IR) tweaked to target a radiation dose similar to a 100 kV single-energy CTPA (SE
      CTPA), i.e., a DLP of 260 mGy cm. Thirty patients (47% men, 64.4yo +/- 18.6, BMI
      26.2 +/- 4.6) from a previous prospective study on DE-CTPA (375 mA fixed tube
      current, reconstruction with filtered-back projection) were used as the reference
      group. Thirty-five consecutive patients (57% men, 65.8yo +/- 15.5, BMI 25.7 +/-
      4.4) who underwent SE-CTPA on the same scanner (automated tube current
      modulation, 50% IR) served as a comparison. Subjective image quality was scored
      by two radiologists using a 5-level scale and compared with a Kruskal-Wallis
      nonparametric test. Density measurements on the 65 keV monochromatic
      reconstructions were used to calculate signal-to-noise (SNR) and contrast-to
      noise (CNR) ratios that were compared using a Student's t test. Correlations
      between image quality, SNR, CNR and BMI were sought using a Pearson's test.
      p<0.05 was considered significant. RESULTS: All examinations were of diagnostic
      quality (score >= 3). In comparison with the reference DE-CTPA and the SE-CTPA
      protocols, the DE-IR group exhibited a non-inferior image quality (p=0.95 and
      p=0.21, respectively) and a significantly lower mean image noise (p<0.01 and
      p=0.01) thus slightly improving the SNR (p=0.09 and p=0.47) and the CNR (p=0.12
      and p=0.51). There was a strong negative relationship between BMI and SNR/CNR
      (rho=-0.59 and -0.55 respectively), but only a moderate negative relationship
      between BMI and image quality (rho=-0.27). CONCLUSION: With iterative
      reconstruction, objective and subjective image quality of single source DE-CTPA
      are preserved even though the radiation dose is lowered to that of a single
      energy examination, overcoming a major limitation of the DE technique and
      allowing a widespread use in the clinical routine.

PMID- 26210095
TI  - Recurrence-free survival in breast cancer is associated with MRI tumor
      enhancement dynamics quantified using computer algorithms.
AB  - PURPOSE: The purpose of this study is to investigate the association between
      breast cancer recurrence-free survival and breast magnetic resonance imaging
      (MRI) tumor enhancement dynamics which are quantified semi-automatically using
      computer algorithms. METHODS: In this retrospective IRB-approved study, we
      analyzed data from 275 breast cancer patients at a single institution. Recurrence
      free survival data were obtained from the medical record. Routine clinical pre
      operative breast MRIs were performed in all patients. The tumors were marked on
      the MRIs by fellowship-trained breast radiologists. A previously developed
      computer algorithm was applied to the marked tumors to quantify the enhancement
      dynamics relative to the automatically assessed background parenchymal
      enhancement. To establish whether the contrast enhancement feature quantified by
      the algorithm was associated with recurrence-free survival, we constructed a Cox
      proportional hazards regression model with the computer-extracted feature as a
      covariate. We controlled for tumor grade and size (major axis length), patient
      age, patient race/ethnicity, and menopausal status. RESULTS: The analysis showed
      that the semi-automatically obtained feature quantifying MRI tumor enhancement
      dynamics was independently predictive of recurrence-free survival (p=0.024).
      CONCLUSION: Semi-automatically quantified tumor enhancement dynamics on MRI are
      predictive of recurrence-free survival in breast cancer patients.

PMID- 26210094
TI  - Intra-thoracic rheumatoid arthritis: Imaging spectrum of typical findings and
      treatment related complications.
AB  - Non-cardiac thoracic manifestations of rheumatoid arthritis (RA) cause
      significant morbidity and mortality among RA patients. Essentially all anatomic
      compartments in the chest can be affected including the pleura, pulmonary
      parenchyma, airway, and vasculature. In addition, treatment-related complications
      and opportunistic infections are not uncommon. Accurate diagnosis of intra
      thoracic disease in an RA patient can be difficult as the radiologic findings may
      be nonspecific and many of these conditions may coexist. This review article
      serves to highlight the multitude of RA-related intra-thoracic pathological
      processes, emphasize differential diagnosis, diagnostic conundrums and discuss
      how tailoring of CT imaging and image-guided biopsy plays a key role in the
      management of RA-related pulmonary disease. 

PMID- 26210096
TI  - Radiation dose and quickness of needle CT-interventions using a laser navigation
      system (LNS) compared with conventional method.
AB  - PURPOSE: The aim of this study was to analyse the radiation dose and quickness of
      needle interventions using a Laser Navigation System (LNS-group) compared with
      conventional method (control-group). MATERIALS AND METHODS: In this prospective,
      randomized, comparative study 58 patients (19 females, 39 males; mean age, 62.9
      years) were punctured either with LNS (n=29) or with conventional method with a
      skin mark of the puncture site (n=29). In the LNS method the puncture site was
      marked with laser without additional CT. Thoracic and abdominal intervention was
      performed in 30 and 28 patients, respectively. Radiation dose and time of the
      procedures were analysed. Statistical significance was calculated according to
      the Mann-Whitney-U-test. RESULTS: Mean target access path in the patients of the
      LNS group was 6.0 cm (range, 3.0-10.1cm) and in the control group 6.0 cm (range,
      1.0-10.3 cm). Time duration of complete intervention in the LNS group was 20:25
      min (range, 07:00-34:00 min) and in the control group 28:00 min (range, 13:00
      51:00 min). The dose-length-product (DLP) of intervention scan of the LNS group
      was 42.3 mGy cm (range, 10-125 mGy cm), and of the control group 59.7 mGy cm
      (range, 25-176.42 mGy cm). CONCLUSION: Using the LNS for CT-guided interventions
      results in faster intervention time with a lower dose.

PMID- 26210097
TI  - Assessment of dietary intake of polychlorinated dibenzo-p-dioxins and
      dibenzofurans and dioxin-like polychlorinated biphenyls from the Chinese Total
      Diet Study in 2011.
AB  - The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) as well as dioxin-like polychlorinated biphenyls (dl-PCBs) were
      measured in food samples from the fifth Chinese Total Diet Study (TDS) performed
      in 2011. A total of 152 composite samples from various food groups were analyzed
      by high resolution gas chromatography-high resolution mass spectrometer (HRGC
      HRMS). The dietary intakes of PCDD/Fs and dl-PCBs were subsequently estimated for
      the adult from various regions in China. The mean dietary intake of PCDD/Fs and
      dl-PCBs was 20.1 pg TEQ kg(-1) bw month(-1) (WHO-TEF of 1998) within a range of
      4.2 pg TEQ kg(-1) bw month(-1) to 53.7 pg TEQ kg(-1) bw month(-1) which were all
      much lower than the provisional tolerable monthly intake (PTMI) established by
      Joint FAO/WHO Expert Committee on Food Additives (JECFA). By comparing with
      results from previous Chinese TDS, a decline of the average dietary intake was
      observed from 2000 to 2011, but a notable elevation was observed in some regions
      partly stem from increasing contamination levels in certain foods.

PMID- 26210098
TI  - Hydroxide ion-mediated synthesis of monodisperse dopamine-melanin nanospheres.
AB  - Dopamine-melanin nanospheres are promising materials for photoprotection,
      structural coloration, and thermoregulation due to their unusual optical and
      chemical properties. Here, we report the experimental parameters which influence
      size of dopamine-melanin nanospheres and uniformity. Dopamine precursors are
      oxidatively polymerized in basic aqueous medium. Therefore, concentration of
      hydroxide ions significantly influences reaction rate and size of nanospheres. To
      investigate the effect of hydroxide ions, we adjust three different parameters
      which affect pH of medium: concentration of sodium hydroxide and dopamine
      hydrochloride, and reaction temperature. At constant temperature, concentration
      of hydroxide ions is linearly proportional to initial reaction rates which
      determine the number of nuclei for nanosphere growth. Temperature alters not only
      initial reaction rate but also diffusivity of molecules, leading to deviation
      from the relation between the reaction rate and the number of nuclei. The
      diameter of dopamine-melanin nanospheres can be readily controlled in a range of
      80-490nm through adjusting concentration of dopamine precursor, while maintaining
      uniform-size distribution and dispersion stability. The synthesized nanospheres
      are analyzed to confirm the chemical structure, which is composed of
      approximately 6 indole units. Moreover, surface and chemical properties of the
      nanospheres are characterized to provide valuable information for surface
      modification and application. 

PMID- 26210099
TI  - Micro/nanostructured porous Fe-Ni binary oxide and its enhanced arsenic
      adsorption performances.
AB  - A simple method is presented to synthesize micro/nano-structured Fe-Ni binary
      oxides based on co-precipitation and subsequent calcination. It has been found
      that the Fe-Ni binary oxides are composed of the porous microsized aggregates
      built with nanoparticles. When the atomic ratio of Fe to Ni is 2 to 1 the binary
      oxide is the micro-scaled aggregates consisting of the ultrafine NiFe2O4
      nanoparticles with 3-6nm in size, and shows porous structure with pore diameter
      of 3nm and a specific surface area of 245m(2)g(-1). Such material is of abundant
      surface functional groups and has exhibited high adsorption performance to
      As(III) and As(V). The kinetic adsorption can be described by pseudo-second order
      model and the isothermal adsorption is subject to Langmuir model. The maximum
      adsorption capacity on such Fe-Ni porous binary oxide is up to 168.6mgg(-1) and
      90.1mgg(-1) for As(III) and As(V), respectively, which are much higher than the
      arsenic adsorption capacity for most commercial adsorbents. Such enhanced
      adsorption ability for this material is mainly attributed to its porous structure
      and high specific surface area as well as the abundant surface functional groups.
      Further experiments have revealed that the influence of the anions such as
      sulfate, carbonate, and phosphate, which commonly co-exist in water, on the
      arsenic adsorption is insignificant, exhibiting strong adsorption selectivity to
      arsenic. This micro/nano-structured porous Fe-Ni binary oxide is hence of good
      practicability to be used as a highly efficient adsorbent for arsenic removal
      from the real arsenic-contaminated waters. 

PMID- 26210100
TI  - Mechanisms of boron removal from hydraulic fracturing wastewater by aluminum
      electrocoagulation.
AB  - HYPOTHESES: Boron uptake from highly saline hydraulic fracturing wastewater by
      freshly precipitated amorphous Al(OH)3 precipitates is due to ligand exchange and
      complexation with surface hydroxyl groups. Consequently, aluminum
      electrocoagulation can be a feasible approach to remove boron from
      flowback/produced water. EXPERIMENTS: Actual hydraulic fracturing wastewater
      containing ~120mg/L boron from the Eagle Ford shale play was employed.
      Electrocoagulation was performed over a range of aluminum dosages (0-1350mg/L),
      pH 6.4 and 8, and high current densities (20-80mA/cm(2)) using a cylindrical
      aluminum anode encompassed by a porous cylindrical 316-stainless steel cathode.
      Direct measurements of boron uptake along with its chemical state and
      coordination were made using Attenuated Total Reflection-Fourier Transform
      Infrared spectroscopy (ATR-FTIR) and X-Ray Photoelectron Spectroscopy. FINDINGS:
      Boron removal increased monotonically with aluminum dosage and was higher at pH
      8, but remained relatively constant at ?20mA/cm(2). Chloride ions induced anodic
      pitting and super-Faradaic (131% efficiency) aluminum dissolution and their
      electrooxidation produced free chlorine. ATR-FTIR suggested outer-sphere and
      inner-sphere complexation of trigonal B(OH)3 with Al(OH)3, which was confirmed by
      the BO bond shifting toward lower binding energies in XPS. Severe AlO
      interferences precluded evidence for tetrahedral B(OH)4(-) complexation. No
      evidence for co-precipitation was obtained.

PMID- 26210101
TI  - Modification of fluorous substrates with oligo(ethylene glycol) via "click"
      chemistry for long-term resistance of cell adhesion.
AB  - In this work perfluorinated substrates fabricated from SiO2 glass slides are
      modified with oligo(ethylene glycol) (OEG) units for long-term resistance of cell
      adhesion purposes, based on fluorous interactions and click chemistry.
      Specifically, fluorous substrates, prepared by treatment of glass slides with 1H,
      1H, 2H, 2H-perfluorodecyltrimethoxysilane (FAS17), were coated with ethynyl-OEG
      C8F17, followed by covalent attachment of an azido-OEG via copper-catalyzed azide
      alkyne cycloaddition (CuAAC) "click" reaction. We demonstrate that the resultant
      surface avoid fibrinogen adsorption and resisted cell adhesion for over 14days. X
      ray photoemission spectroscopy (XPS) analysis and contact angle goniometry
      measurements confirm the presence of the OEG molecules on the fluorous
      substrates. Bright field optical images show total absence of 3T3 fibroblast
      cells on the OEG modified fluorinated substrate for 1 and 5days, and a remarkably
      decrease of cell adhesion at 14days. 

PMID- 26210102
TI  - Synthesis and characterization of pH-sensitive poly(itaconic acid)-poly(ethylene
      glycol)-folate-poly(l-histidine) micelles for enhancing tumor therapy and tunable
      drug release.
AB  - pH responsive intracellular tumor targeting is increasingly investigated as a
      pathway to trigger the release of anti-tumor drugs once the drug carrier reached
      the unique acidic environment of the solid tumors or after the drug carrier has
      been taken up by cells, resulting in the localization of the micelles in the
      acidic endosomes and lysosomes. Poly(itaconic acid)-poly(ethylene glycol)-folate
      poly(l-histidine) (PIA-PEG-FA-PHIS) was synthesized as a carrier for tumor
      targeted drug delivery. The micelles were internalized by receptor-mediated
      endocytosis, and the combination of active targeting and triggered release
      resulted in apparent cytotoxicity and antitumor activity. The MTT assay showed
      DOX-loaded micelles had higher and obvious cytotoxicity against Hela cells at pH
      5.0 than that at pH 7.4. Cellular uptake experiments revealed that these pH
      responsive PIA-PEG-FA-PHIS micelles were taken up in great amounts by receptor
      mediated endocytosis and delivered to lysosomes, triggering release of DOX into
      the cytoplasm. These indicated that the PIA-PEG-FA-PHIS micelles could be a
      promising drug delivery system with preeminent stability for targeting the
      hydrophobic drugs to cancer cells and releasing DOX in to the cells by sensing
      the acidic environment of the endosomes for cancer therapy. 

PMID- 26210103
TI  - Molecular landscape of prostate cancer: implications for current clinical trials.
AB  - Castration-resistant prostate cancer (CRPC) is a lethal disease, and improvement
      with androgen-deprivation therapy has plateaued. Next-generation sequencing
      studies have led to significant advances in our understanding of genomic
      alterations in prostate cancer. The most common genomic aberrations in this
      malignancy are the transcription factor fusion of TMPRSS2-ETS, and mutations in
      TP53, AR, RB1 and PTEN/PIK3CA. Some of these alterations are actionable by drugs
      available in the clinic. In addition, it was recently shown that aberrations in
      DNA repair genes, such as BRCA2 and ATM, are present in both somatic and germline
      form in a significant minority of prostate cancer; these abnormalities can be
      targeted by drugs such as platinums and PARP inhibitors. In the era of tumour
      profiling, targeting molecular alterations may provide an opportunity for new
      therapeutic approaches. Although there are promising new agents to attack a
      variety of genomic signal abnormalities, biomarker-matched therapy (other than
      for androgens) have been utilised in only 2.0% of clinical trials (September 2011
      through September 2014; https://clinicaltrials.gov) for prostate cancer. Enhanced
      efforts to define subsets of patients with prostate cancer based on their
      molecular anomalies, and match them with cognate therapies, warrant
      investigation. 

PMID- 26210104
TI  - Drosophila immune cell migration and adhesion during embryonic development and
      larval immune responses.
AB  - The majority of immune cells in Drosophila melanogaster are plasmatocytes; they
      carry out similar functions to vertebrate macrophages, influencing development as
      well as protecting against infection and cancer. Plasmatocytes, sometimes
      referred to with the broader term of hemocytes, migrate widely during embryonic
      development and cycle in the larvae between sessile and circulating positions.
      Here we discuss the similarities of plasmatocyte developmental migration and its
      functions to that of vertebrate macrophages, considering the recent controversy
      regarding the functions of Drosophila PDGF/VEGF related ligands. We also examine
      recent findings on the significance of adhesion for plasmatocyte migration in the
      embryo, as well as proliferation, trans-differentiation, and tumor responses in
      the larva. We spotlight parallels throughout to vertebrate immune responses. 

PMID- 26210105
TI  - The CydDC Family of Transporters and Their Roles in Oxidase Assembly and
      Homeostasis.
AB  - The CydDC complex of Escherichia coli is a heterodimeric ATP-binding cassette
      type transporter (ABC transporter) that exports the thiol-containing redox-active
      molecules cysteine and glutathione. These reductants are thought to aid redox
      homeostasis of the periplasm, permitting correct disulphide folding of
      periplasmic and secreted proteins. Loss of CydDC results in the periplasm
      becoming more oxidising and abolishes the assembly of functional bd-type
      respiratory oxidases that couple the oxidation of ubiquinol to the reduction of
      oxygen to water. In addition, CydDC-mediated redox control is important for haem
      ligation during cytochrome c assembly. Given the diverse roles for CydDC in redox
      homeostasis, respiratory metabolism and the maturation of virulence factors, this
      ABC transporter is an intriguing system for researchers interested in both the
      physiology of redox perturbations and the role of low-molecular-weight thiols
      during infection. 

PMID- 26210106
TI  - A Post-Genomic View of the Ecophysiology, Catabolism and Biotechnological
      Relevance of Sulphate-Reducing Prokaryotes.
AB  - Dissimilatory sulphate reduction is the unifying and defining trait of sulphate
      reducing prokaryotes (SRP). In their predominant habitats, sulphate-rich marine
      sediments, SRP have long been recognized to be major players in the carbon and
      sulphur cycles. Other, more recently appreciated, ecophysiological roles include
      activity in the deep biosphere, symbiotic relations, syntrophic associations,
      human microbiome/health and long-distance electron transfer. SRP include a high
      diversity of organisms, with large nutritional versatility and broad metabolic
      capacities, including anaerobic degradation of aromatic compounds and
      hydrocarbons. Elucidation of novel catabolic capacities as well as progress in
      the understanding of metabolic and regulatory networks, energy metabolism,
      evolutionary processes and adaptation to changing environmental conditions has
      greatly benefited from genomics, functional OMICS approaches and advances in
      genetic accessibility and biochemical studies. Important biotechnological roles
      of SRP range from (i) wastewater and off gas treatment, (ii) bioremediation of
      metals and hydrocarbons and (iii) bioelectrochemistry, to undesired impacts such
      as (iv) souring in oil reservoirs and other environments, and (v) corrosion of
      iron and concrete. Here we review recent advances in our understanding of SRPs
      focusing mainly on works published after 2000. The wealth of publications in this
      period, covering many diverse areas, is a testimony to the large environmental,
      biogeochemical and technological relevance of these organisms and how much the
      field has progressed in these years, although many important questions and
      applications remain to be explored. 

PMID- 26210107
TI  - Neisserial Molecular Adaptations to the Nasopharyngeal Niche.
AB  - The exclusive reservoir of the genus Neisseria is the human. Of the broad range
      of species that comprise the Neisseria, only two are frequently pathogenic, and
      only one of those is a resident of the nasopharynx. Although Neisseria
      meningitidis can cause severe disease if it invades the bloodstream, the vast
      majority of interactions between humans and Neisseria are benign, with the
      bacteria inhabiting its mucosal niche as a non-invasive commensal.
      Understandably, with the exception of Neisseria gonorrhoeae, which preferentially
      colonises the urogenital tract, the neisseriae are extremely well adapted to
      survival in the human nasopharynx, their sole biological niche. The purpose of
      this review is to provide an overview of the molecular mechanisms evolved by
      Neisseria to facilitate colonisation and survival within the nasopharynx,
      focussing on N. meningitidis. The organism has adapted to survive in aerosolised
      transmission and to attach to mucosal surfaces. It then has to replicate in a
      nutrition-poor environment and resist immune and competitive pressure within a
      polymicrobial complex. Temperature and relative gas concentrations (nitric oxide
      and oxygen) are likely to be potent initial signals of arrival within the
      nasopharyngeal environment, and this review will focus on how N. meningitidis
      responds to these to increase the likelihood of its survival. 

PMID- 26210108
TI  - Marine Microbial Secondary Metabolites: Pathways, Evolution and Physiological
      Roles.
AB  - Microbes produce a huge array of secondary metabolites endowed with important
      ecological functions. These molecules, which can be catalogued as natural
      products, have long been exploited in medical fields as antibiotics, anticancer
      and anti-infective agents. Recent years have seen considerable advances in
      elucidating natural-product biosynthesis and many drugs used today are natural
      products or natural-product derivatives. The major contribution to recent
      knowledge came from application of genomics to secondary metabolism and was
      facilitated by all relevant genes being organised in a contiguous DNA segment
      known as gene cluster. Clustering of genes regulating biosynthesis in bacteria is
      virtually universal. Modular gene clusters can be mixed and matched during
      evolution to generate structural diversity in natural products. Biosynthesis of
      many natural products requires the participation of complex molecular machines
      known as polyketide synthases and non-ribosomal peptide synthetases. Discovery of
      new evolutionary links between the polyketide synthase and fatty acid synthase
      pathways may help to understand the selective advantages that led to evolution of
      secondary-metabolite biosynthesis within bacteria. Secondary metabolites confer
      selective advantages, either as antibiotics or by providing a chemical language
      that allows communication among species, with other organisms and their
      environment. Herewith, we discuss these aspects focusing on the most clinically
      relevant bioactive molecules, the thiotemplated modular systems that include
      polyketide synthases, non-ribosomal peptide synthetases and fatty acid synthases.
      We begin by describing the evolutionary and physiological role of marine natural
      products, their structural/functional features, mechanisms of action and
      biosynthesis, then turn to genomic and metagenomic approaches, highlighting how
      the growing body of information on microbial natural products can be used to
      address fundamental problems in environmental evolution and biotechnology. 

PMID- 26210109
TI  - Anti-proliferative activity and chemical characterization by comprehensive two
      dimensional liquid chromatography coupled to mass spectrometry of phlorotannins
      from the brown macroalga Sargassum muticum collected on North-Atlantic coasts.
AB  - In the present work, the phlorotannin composition of different Sargassum muticum
      samples collected at different locations along the North Atlantic coasts as well
      as the bioactivities related to these components were investigated. After
      pressurized liquid extraction, the samples collected at the extreme locations of
      a latitudinal gradient from Portugal and Norway, were found to be the richest on
      total phenols and, particularly, on phlorotannins, containing up to 148.97 and
      5.12mg phloroglucinol equivalents g(-1), respectively. The extracts obtained from
      these locations were further purified and chemically characterized using a
      modified HILIC*RP-DAD-MS/MS method. The application of this methodology allowed
      the tentative identification of a great variability of phlorotannins with
      different degrees of polymerization (from 3 to 11) and structures, determined for
      the first time in S. muticum. The most-abundant phlorotannins on these samples
      were fuhalols, hydroxyfuhalols and phlorethols, showing also particularities and
      important differences depending on the geographical location. Afterwards, the
      antiproliferative activity of these extracts against HT-29 adenocarcinoma colon
      cancer cells was studied. Results revealed that the richest S. muticum samples in
      terms of total phlorotannins, i.e., those from Norway, presented the highest
      activity, showing a good cytotoxic potential at concentrations in the medium
      micromolar range. 

PMID- 26210110
TI  - Quantitative evaluation of models for solvent-based, on-column focusing in liquid
      chromatography.
AB  - On-column focusing or preconcentration is a well-known approach to increase
      concentration sensitivity by generating transient conditions during the injection
      that result in high solute retention. Preconcentration results from two
      phenomena: (1) solutes are retained as they enter the column. Their velocities
      are k'-dependent and lower than the mobile phase velocity and (2) zones are
      compressed due to the step-gradient resulting from the higher elution strength
      mobile phase passing through the solute zones. Several workers have derived the
      result that the ratio of the eluted zone width (in time) to the injected time
      width is the ratio k2/k1, where k1 is the retention factor of a solute in the
      sample solvent and k2 is the retention factor in the mobile phase (isocratic).
      Mills et al. proposed a different factor. To date, neither of the models has been
      adequately tested. The goal of this work was to evaluate quantitatively these two
      models. We used n-alkyl esters of p-hydroxybenzoic acid (parabens) as solutes. By
      making large injections to create obvious volume overload, we could measure
      accurately the ratio of widths (eluted/injected) over a range of values of k1 and
      k2. The Mills et al. model does not fit the data. The data are in general
      agreement with the factor k2/k1, but focusing is about 10% better than the
      prediction. We attribute the extra focusing to the fact that the second,
      compression, phenomenon provides a narrower zone than that expected for the
      passage of a step gradient through the zone. 

PMID- 26210111
TI  - A salting out system for improving the efficiency of the headspace solid-phase
      microextraction of short and medium chain free fatty acids.
AB  - Given the importance of short and medium chain free fatty acids (FFAs) in several
      fields, this study sought to improve the extraction efficiency of the solid-phase
      microextraction (SPME) of FFAs by evaluating salting out agents that appear
      promising for this application. The salts ammonium sulfate ((NH4)2SO4) and sodium
      dihydrogen phosphate (NaH2PO4) were tried on their own and in combination
      (3.7/1), in four different total amounts, as salting out agents in the headspace
      SPME-gas chromatographic (HS-SPME-GC) analysis of the FFAs from acetic acid (C2)
      to decanoic acid (C10). Their performance in a model system of an aqueous
      standard mixture of FFAs at a pH of 3.5 was compared to that of the more commonly
      used sodium chloride (NaCl) and sodium sulfate (Na2SO4). All of the salts and
      salt systems evaluated, in proper amount, gave improved results compared to NaCl
      (saturated), which instead gave interesting results only for the least volatile
      FFAs C8 and C10. For C2-C6, the salt system that gave the best results compared
      to NaCl was (NH4)2SO4/NaH2PO4, in the highest of the four amounts evaluated, with
      factor increases between 1.2 and 4.1-fold, and NaH2PO4, between 1.0 and 4.3-fold.
      The SPME extraction efficiency given by the mixture (NH4)2SO4/NaH2PO4 was also
      assessed on biological and food samples, confirming that overall it performed
      better than NaCl. 

PMID- 26210112
TI  - Scale-up in centrifugal partition chromatography: The "free-space between peaks"
      method.
AB  - Centrifugal Partition Chromatography (CPC) is a purification technique using a
      biphasic liquid system. As a preparative separation technique, scale-up is of
      primary concern. Once the separation is optimized on a lab-scale instrument, the
      scale-up transfer is quite straightforward simply using the instrument volume
      ratio as the linear transfer factor, thanks to the absence of solid support. Such
      linear transfer underestimates the performances of large-scale CPC rotors that
      are usually better than that of small rotors. It means that more material than
      predicted by the linear estimation could be purified. A fully practical method
      based on experimental observations is proposed. The first step is to determine
      experimentally the free space volume available between the two peaks of interest
      doing two analytical separations, one with the small analytical CPC instrument,
      giving DeltaV1, and the second with the large preparative one, giving DeltaV2.
      The second step is to determine on the small CPC instrument how much material can
      be loaded to reach the maximum mass load still giving the required purity and
      recovery ratio of the desired compound. Then, an accurate prediction of the
      maximal quantity of sample that the large-scale rotor can purify is simply
      obtained by multiplying the maximum mass load on the analytical CPC instrument by
      the free-space between peaks DeltaV2/DeltaV1 ratio. For demonstration purposes,
      the method is applied to the transfer of the CPC separation of a synthetic three
      GUESS-compound mixture from a 35mL-rotor to a semi-prep 239-mL rotor. The paper
      addresses also the operating condition optimization depending on industrial
      production strategy (maximal load per run or maximal productivity). 

PMID- 26210114
TI  - Compound identification in gas chromatography/mass spectrometry-based
      metabolomics by blind source separation.
AB  - Metabolomics GC-MS samples involve high complexity data that must be effectively
      resolved to produce chemically meaningful results. Multivariate curve resolution
      alternating least squares (MCR-ALS) is the most frequently reported technique for
      that purpose. More recently, independent component analysis (ICA) has been
      reported as an alternative to MCR. Those algorithms attempt to infer a model
      describing the observed data and, therefore, the least squares regression used in
      MCR assumes that the data is a linear combination of that model. However, due to
      the high complexity of real data, the construction of a model to describe
      optimally the observed data is a critical step and these algorithms should
      prevent the influence from outlier data. This study proves independent component
      regression (ICR) as an alternative for GC-MS compound identification. Both ICR
      and MCR though require least squares regression to correctly resolve the
      mixtures. In this paper, a novel orthogonal signal deconvolution (OSD) approach
      is introduced, which uses principal component analysis to determine the compound
      spectra. The study includes a compound identification comparison between the
      results by ICA-OSD, MCR-OSD, ICR and MCR-ALS using pure standards and human serum
      samples. Results shows that ICR may be used as an alternative to multivariate
      curve methods, as ICR efficiency is comparable to MCR-ALS. Also, the study
      demonstrates that the proposed OSD approach achieves greater spectral resolution
      accuracy than the traditional least squares approach when compounds elute under
      undue interference of biological matrices. 

PMID- 26210113
TI  - Pentacyclic triterpene in Olea europaea L: A simultaneous determination by high
      performance liquid chromatography coupled to mass spectrometry.
AB  - Pentacyclic triterpenes are gaining interest due to their beneficial health
      effects, as anti-inflammatory, anti-diabetic and anti-tumoral, among others. In
      this study, an analytical LC-MS method was developed for the simultaneous
      determination of maslinic, oleanolic and ursolic acids along with erythrodiol and
      uvaol, which are the main triterpenic compounds present in the fruits and leaves
      of Olea europaea L. A Zorbax Eclipse PAH column at 30 degrees C with mobile phase
      of water (17%) and methanol (83%) at 0.8mL/min conformed the optimal
      chromatographic conditions that allowed the separation of the compounds of
      interest, two pairs of which are isomers differing only in the position of one
      methyl group (oleanolic-ursolic and erythrodiol-uvaol). The ionization was
      performed in an APCI source at 450 degrees C programmed in negative mode for the
      triterpenic acids, and in positive for the alcohols. An ion trap (LC-IT-MS) and a
      triple quadrupole (LC-QqQ-MS) were assessed for maximal sensitivity that was
      achieved with LC-QqQ-MS. The LODs of triterpenic acids were lower than 1nM,
      whereas for erythrodiol and uvaol were 4.5 and 7.5nM, respectively. The method
      was linear for the five analytes in the range of concentrations from 0.005 to
      15MUM with correlation coefficients exceeding 0.99. The precision and accuracy
      were <=9.90% and <=9.57%, respectively. The applicability of the validated method
      was assessed in the analysis of the pentacyclic triterpenes in Marfil table
      olives, after the optimization of the extraction procedure. The developed method
      constitutes the first step for future studies of triterpenic compounds present in
      foods that would allow establishing their effects on human health. 

PMID- 26210115
TI  - Towards determination of absolute molar mass of cellulose polymer by size
      exclusion chromatography with mulitple angle laser light scattering detection.
AB  - The study focuses on determination of a set of crucial parameters for molar mass
      calculation of cellulose from the results of size exclusion chromatography
      coupled with multiple angle laser light scattering (MALLS) and differential
      refractive index (DRI) detectors. In the present work, cellulose has been
      derivatised to obtain cellulose tricarbanilate (CTC) soluble in tetrahydrofuran
      (THF). The parameters of Rayleigh scattering in the MALLS detector: refractive
      index increment (dn/dc) and second virial coefficient (A2) of CTC in THF were
      determined for laser wavelength 658nm. In order to avoid errors resulting from
      cellulose derivatisation by-products present in the CTC solution, the so called
      "on-line" method of measuring dn/dc and A2 was applied. Based on the A2
      determination, its influence on cellulose molar mass calculations and cellulose
      molecular dimensions were critically assessed. The latter includes evaluation of
      artificially aged cellulose towards conceivable branching by conformation plot
      analysis. 

PMID- 26210116
TI  - Recent Trends in Alcohol Outlet Density, Distances from Educational Institutions
      and Sales Campaigns in Chiang Mai Municipality (Metropolitan), Thailand: Should
      We Be Worried for Our Youths?
AB  - AIMS: Since 2008, alcohol control policies in Thailand have been considered quite
      comprehensive. The study aimed to investigate the subsequent changes in alcohol
      outlet density and patterns of sales promotion, which may be useful for
      monitoring the effectiveness of policies and helpful for planning prevention
      strategies to reduce alcohol-related harms. METHODS: All accessible routes in the
      Chiang Mai Municipality (Metropolitan: CMM) were surveyed in 2009, 2011 and 2014.
      During each round of survey, the geographical coordinates of alcohol outlets and
      educational institutions in the CMM were recorded using the Global Navigation
      Satellite System (GNSS). In addition, alcohol sales campaigns were documented.
      RESULTS: Three main trends emerged by 2014. The first was that alcohol outlet
      density had increased. Second, the average distances between alcohol outlets and
      educational institutions decreased with evidence of clustering near educational
      institutions. Lastly, increased advertising of alcohol promotions and new sales
      campaigns not previously seen in 2009 and 2011 promoted high volume drinking in
      Chiang Mai Municipality (CMM). CONCLUSION: Our study reflects the potential gaps
      between some of the intended consequences of alcohol control policies and the
      actural trends emerging in Chiang Mai, Thailand. Young people in CMM may be at a
      particularly high risk for alcohol-related problems due to high exposure to
      alcohol outlets and sales campaigns near their educational institution.

PMID- 26210117
TI  - [The digital ravine].

PMID- 26210118
TI  - [Dentistry in the Middle Ages in the low lands 4. "Van den tanden die siin
      gegaet"].

PMID- 26210119
TI  - [Immediate front implant placements 2. Objective and subjective aesthetic
      treatment results].
AB  - In this study, the aesthetic outcome of treatment was analysed after immediate
      implant placement in 16 patients. During implant installation the gap between the
      implant and the buccal plate was filled with a bone substitute. Only single tooth
      replacements were included; the final crowns were placed 3-6 months after implant
      installation, all with individual manufactured abutments with an emerging profile
      and platform switching. Postoperative aesthetics were analysed based on clinical
      photographs and satisfactionquestionnaires. The objectively attained White
      Esthetic Score and Pink Esthetic Score with an average value of 8.4 and 11.8
      respectively, scored high, as was also observed for patient's satisfaction on
      both treatment and outcome (an average of 8.7). It may be concluded that flapless
      immediate implant placement together with the application of a bone substitute
      into the buccal gap in combination with a final crown with emerging profile
      results in objective and subjective good aesthetics and high patient
      satisfaction. 

PMID- 26210120
TI  - [Caries prevention strategies for 6-year-olds. A randomized controlled study].
AB  - A randomized controlled study of caries prevention strategies was conducted on
      patients with a mixed socioeconomic status in a large general dental practice in
      the Netherlands. A group of children following a non-operative caries treatment
      programme (NOCTP) was compared to a control group and a group that also received
      2 topical fluoride applications (IPFA) as a supplement to the control programme
      (receiving a dental check-up twice a year with topical fluoride applications and
      routinely sealing of the first permanent molars). A total of 230 6-year-old
      children were randomly assigned to one of these groups. After 3 years, 179
      children were studied again (54 NOCTP, 62 IPFA and 63 controls). Caries-increment
      was lowest in the NOCTP group (0.15 DMFS). In the IPFA group and the control
      group DMFS-increments were 0.34 and 0.47 respectively. Although the results of
      this study are very promising, a follow-up study on a larger scale is required to
      make clear whether the application of NOCTP is more effective than standard
      prevention in general practice. 

PMID- 26210121
TI  - [The impact of frailty on the oral care behaviour and dental service use of
      elderly people].
AB  - In order to explore how the level of frailty and various frailty factors affect
      the dental service use and oral self-care behaviour of frail elderly people, 51
      frail elderly people were interviewed. Additional information on age, gender,
      living situation, prosthetic status, self-reported health and oral health,
      chronic diseases and an index for frailty was collected. A thematic qualitative
      analysis of the collected data reveals that frail elders maintain long
      established oral hygiene routines as long as possible to sustain a sense of self
      worth. When burdened by severe health complaints they discontinue visits to the
      dentist first and oral hygiene routines subsequently. A loss of confidence in the
      results of dental service use, the trivializing of complaints and a diminishing
      sense of the importance of oral health play a role in these developments. Frail
      elderly people also experience psychological and social barriers to oral
      healthcare and dental service use when they are institutionalized. 

PMID- 26210122
TI  - [Monitoring steam sterilisation processes in the dental office].
AB  - In dental offices, steam sterilisation is used to sterilise instruments and in
      that way to prevent the cross-contamination of patients and the dental team. In
      order to ensure that the sterilisation process has been executed successfully,
      every sterilisation process has to be monitored. The monitoring of every load in
      the steam steriliser is necessary and often even required, either directly (by
      legislation) or indirectly (by harmonised standards). The complete monitoring
      protocol consists of controls of the installation, the exposure, the loading, the
      packaging and, finally, the 'track and trace' of the instruments. For examining
      the installation, a steam penetration test, such as the Bowie and Dick test, can
      be carried out. 

PMID- 26210124
TI  - The Pathogenesis of Systemic Sclerosis.
AB  - Systemic sclerosis is a multisystem disorder with a high associated mortality.
      The hallmark abnormalities of the disease are in the immune system, vasculature,
      and connective tissue. Systemic sclerosis occurs in susceptible individuals and
      is stimulated by initiating events that are poorly understood at present. In
      order for the disease phenotype to appear there is dysfunction in the
      homoeostatic mechanisms of immune tolerance, endothelial physiology, and
      extracellular matrix turnover. The progression of disease is not sequential but
      requires simultaneous dysfunction in these normal regulatory mechanisms. Better
      understanding of the interplay of these factors is likely to contribute to
      improved treatment options. 

PMID- 26210125
TI  - New Classification Criteria for Systemic Sclerosis (Scleroderma).
AB  - The American College of Rheumatology (ACR)/European League Against Rheumatism
      (EULAR) criteria for the classification of systemic sclerosis (SSc) were
      developed to classify more patients with SSc for studies and improve on previous
      criteria. The new classification criteria have the following criteria: skin
      thickening of the fingers extending proximal to the metacarpophalangeal joints.
      Seven additive items are each given a numerical weight: skin thickening,
      fingertip lesions, telangiectasia, abnormal nail fold capillaries, lung
      involvement, Raynaud's phenomenon, and SSc-related autoantibodies. The ACR/EULAR
      classification criteria for SSc have good sensitivity and specificity but do not
      substitute for diagnostic criteria. 

PMID- 26210123
TI  - Genetics, Epigenetics, and Genomics of Systemic Sclerosis.
AB  - Systemic sclerosis (SSc) is a complex autoimmune disease that occurs in a
      genetically susceptible host. Genetic studies performed so far reveal that
      multiple genetic loci contribute to disease susceptibility in SSc. The purpose of
      this review is to discuss the current knowledge of genetics in SSc by exploring
      the observational evidence, the different genetic studies, and their modalities
      as well as the most relevant genes discovered by these. The importance of gene
      expression variation and the different mechanisms that govern it, including the
      recently discovered field of epigenetics, are also explored, with an emphasis on
      microRNA. 

PMID- 26210126
TI  - Management of Systemic Sclerosis-Related Skin Disease: A Review of Existing and
      Experimental Therapeutic Approaches.
AB  - The skin is the most common organ system involved in patients with systemic
      sclerosis (SSc). Nearly all patients experience cutaneous symptoms, including
      sclerosis, Raynaud's phenomenon, digital ulcers, telangiectasias, and calcinosis.
      In addition to posing functional challenges, cutaneous symptoms are often a major
      cause of pain, psychological distress, and body image dissatisfaction. The
      present article reviews the main features of SSc-related cutaneous manifestations
      and highlights an evidence-based treatment approach for treating each
      manifestation. This article also describes novel treatment approaches and
      opportunities for further research in managing this important clinical dimension
      of SSc. 

PMID- 26210127
TI  - Management of Raynaud Phenomenon and Digital Ulcers in Scleroderma.
AB  - Raynaud phenomenon (RP) and associated digital ischemia can be among the most
      vexing clinical problems for patients with systemic sclerosis (scleroderma).
      Understanding the treatment approach to RP and associated ischemia and how to
      prevent digital ulcers is important for clinicians caring for these patients.
      This article reviews the management of RP and digital ischemic ulcers. The
      magnitude of the problem and pathophysiology of RP are first discussed, with an
      emphasis on recent advances in understanding of the disease process. Options for
      the practical pharmacologic and nonpharmacologic interventions for RP and digital
      ischemic ulcers are detailed. 

PMID- 26210129
TI  - Systemic Sclerosis: Gastrointestinal Disease and Its Management.
AB  - The gastrointestinal tract, affecting more than 90% of patients, is the internal
      organ most frequently involved in systemic sclerosis. Any part of the
      gastrointestinal tract can be affected, from the mouth to the anus. Patients
      often experience reduced quality of life and impaired social life. Although only
      8% have severe gastrointestinal involvement, mortality is high in those patients.
      Recent studies on the pathophysiology of the disease highlight new mechanisms to
      explain gastrointestinal dysmotility, but treatment remains symptomatic. This
      article reviews the pathophysiology of the gastrointestinal tract and discusses
      the investigation and management of the disease. 

PMID- 26210128
TI  - Management of Systemic-Sclerosis-Associated Interstitial Lung Disease.
AB  - Although scleroderma-associated interstitial lung disease (SSc-ILD) is a
      significant contributor to both morbidity and mortality, its pathogenesis is
      largely unclear. Pulmonary function tests and high-resolution computed
      tomographic scanning continue to be the most effective tools to screen for lung
      involvement and to monitor for disease progression. More research and better
      biomarkers are needed to identify patients most at risk for developing SSc-ILD as
      well as to recognize which of these patients will progress to more severe
      disease. Although immunosuppression remains the mainstay of treatment,
      antifibrotic agents may offer new avenues of treatment for patients with SSc-ILD
      in the future. 

PMID- 26210130
TI  - Scleroderma Renal Crisis.
AB  - Scleroderma renal crisis is a rare complication of systemic sclerosis (SSc) that
      remains severe. Prompt recognition and initiation of therapy with an angiotensin
      converting-enzyme inhibitor offer the best chance to achieve a good outcome. SSc
      prevalence is poorly known, with disparities among countries. 

PMID- 26210131
TI  - Monitoring and Diagnostic Approaches for Pulmonary Arterial Hypertension in
      Patients with Systemic Sclerosis.
AB  - Pulmonary arterial hypertension (PAH) is one of the leading causes of death in
      patients with systemic sclerosis (SSc). Given the high prevalence and poor
      survival of SSc-PAH, and that aggressive management of mild disease may be
      associated with better outcomes, screening is critical. Right heart
      catheterization (RHC) is the gold standard for the definitive diagnosis of PAH,
      and should be performed in those patients in whom this diagnosis is suspected.
      Once a diagnosis of PAH is confirmed by RHC, treatment with PAH-specific
      therapies should be initiated as soon as possible. 

PMID- 26210132
TI  - Musculoskeletal Manifestations of Systemic Sclerosis.
AB  - Systemic sclerosis (SSc; scleroderma) is a chronic autoimmune connective tissue
      disease characterized by microvascular obliteration and sclerosis of the skin and
      internal organs. Although the clinical hallmark of the disease is the appearance
      of taut tethering of the skin, one of the earliest manifestations of SSc is a
      painful symmetrical arthropathy ranging from minimal arthralgia to overt
      polyarthritis. Musculoskeletal (MSK) involvement in SSc occurs more frequently
      than expected. Arthralgia is the most commonly reported manifestation. Some of
      the existing composite and organ-specific indices of disease activity and/or
      disease severity in SSc include MSK manifestations. 

PMID- 26210133
TI  - Psychosocial Aspects of Scleroderma.
AB  - Patients with systemic sclerosis (SSc; also called scleroderma) have to cope with
      not only the physical impacts of the disease but also the emotional and social
      consequences of living with the condition. Because there is no cure for SSc,
      improving quality of life is a primary focus of treatment and an important
      clinical challenge. This article summarizes significant problems faced by
      patients with SSc, including depression, anxiety, fatigue, sleep disruption,
      pain, pruritus, body image dissatisfaction, and sexual dysfunction, and describes
      options to help patients cope with the consequences of the disease. 

PMID- 26210134
TI  - Systemic Sclerosis.

PMID- 26210135
TI  - Systemic Sclerosis.

PMID- 26210136
TI  - Use of a capacity audit tool in a mental health setting.
AB  - OBJECTIVE: This paper reports on a pilot applying the capacity audit tool (CAT)
      in a mental health environment and what the tool reveals regarding mental health
      in-patient capacity issues. METHODS: The CAT was modified to create an electronic
      mental health-relevant tool to audit acute in-patient capacity. This tool was
      then piloted across nine bedded units, within a single Local Health Network,
      covering a total of 153 mental health beds. RESULTS: The application of the
      mental health CAT resulted in 100% compliance in completion. The findings
      revealed that 16% (25 beds) of the 153 beds surveyed were occupied by patients
      who did not need to occupy the bed or the bed was vacant. Of these 25 beds, 10
      had patients awaiting transfer to another facility or service, nine were empty
      and six were occupied by patients ready for discharge but for whom there were
      delays. CONCLUSION: The CAT was successfully applied to the mental health setting
      and identified a set of opportunities to improve processes and practices to
      reduce the identified delays or barriers in order to improve patient flow.

PMID- 26210137
TI  - Improving hydrolysis acidification by limited aeration in the pretreatment of
      petrochemical wastewater.
AB  - Petrochemical wastewater was pretreated by hydrolysis acidification to improve
      the biodegradation and treatability on limited aeration conditions. The results
      showed limited aeration with DO from 0.2 to 0.3mg/L (average ORP was -210 mV) was
      the best condition. The BOD5/COD of influent was 0.23, and it increased to 0.43
      on this condition. Limited aeration can obviously reduce the reduction of SO4(2
      ), reducing the generation of toxic gas H2S, and almost no H2S can be detected in
      the off-gas. The sulfate reducing bacteria (SRB) diversity and abundance on
      limited aeration condition was obviously inhibited. Limited aeration condition
      was benefit for the removal of benzene ring organics, such as benzene, toluene,
      ethylbenzene and xylenes (BTEX), improving the toxicity and treatability of the
      wastewater. Based on the experiment results, an anaerobic hydrolysis
      acidification tank (100,000 m(3)) has been transformed into limited aeration
      hydrolysis acidification tank and it runs well.

PMID- 26210138
TI  - Simultaneous saccharification and fermentation of steam exploded duckweed:
      Improvement of the ethanol yield by increasing yeast titre.
AB  - This study investigated the conversion of Lemna minor biomass to bioethanol. The
      biomass was pre-treated by steam explosion (SE, 210 degrees C, 10 min) and then
      subjected to simultaneous saccharification and fermentation (SSF) using Cellic(r)
      CTec 2 (20 U or 0.87 FPU g(-1) substrate) cellulase plus beta-glucosidase (2 U g(
      1) substrate) and a yeast inoculum of 10% (v/v or 8.0*10(7) cells mL(-1)). At a
      substrate concentration of 1% (w/v) an ethanol yield of 80% (w/w, theoretical)
      was achieved. However at a substrate concentration of 20% (w/v), the ethanol
      yield was lowered to 18.8% (w/w, theoretical). Yields were considerably improved
      by increasing the yeast titre in the inoculum or preconditioning the yeast on
      steam exploded liquor. These approaches enhanced the ethanol yield up to 70%
      (w/w, theoretical) at a substrate concentration of 20% (w/v) by metabolising
      fermentation inhibitors.

PMID- 26210139
TI  - Highly charged cellulose-based nanocrystals as flocculants for harvesting
      Chlorella vulgaris.
AB  - This study presents a novel flocculant for harvesting Chlorella vulgaris as model
      species for freshwater microalgae based on cellulose nanocrystals (CNCs), thus
      synthesized from a renewable and biodegradable resource. Cationic pyridinium
      groups were grafted onto CNCs by two separate one-pot simultaneous esterification
      and nucleophilic substitution reactions. Both types of modified CNCs were
      positively charged in the pH range 4-11. Both reactions yielded CNCs with a high
      degree of substitution (up to 0.38). A maximum flocculation efficiency of 100%
      was achieved at a dosage of 0.1 g g(-1) biomass. In contrast to conventional
      polymer flocculants, cationic CNCs were relatively insensitive to inhibition of
      flocculation by algal organic matter. The present results highlight the potential
      of these new type of nanocellulose-based flocculants for microalgae harvesting.

PMID- 26210140
TI  - Potential biodiesel and biogas production from corncob by anaerobic fermentation
      and black soldier fly.
AB  - Bioenergy has become attractive as alternatives of gradually exhausted fossil
      fuel. Obtaining high grade bioenergy from lignocellulose is attractive that can
      gradually meet the demand. This study reported biogas and biodiesel were produced
      from corncob by a two-step bioprocess, biogas was produced from corncob by
      anaerobic fermentation, then biogas residue was converted by black soldier fly
      larvae, and then biodiesel was produced from larvae grease. 86.70 L biogas was
      obtained from 400 g corncob with the accumulation of biogas yield of 220.71 mL/g
      VS(added) by anaerobic digestion. Besides, 3.17 g of biodiesel was produced from
      grease after inoculating black soldier fly larvae into 400 g biogas residue.
      Meanwhile, the results showed that the addition of black soldier fly larvae could
      be effective for the degradation of lignocellulose and the accumulation of
      grease.

PMID- 26210141
TI  - Semi-continuous anaerobic co-digestion of sugar beet byproduct and pig manure:
      Effect of the organic loading rate (OLR) on process performance.
AB  - Anaerobic co-digestion of dried pellet of exhausted sugar beet cossettes (ESBC
      DP) with pig manure (PM) was investigated in a semi-continuous stirred tank
      reactor (SSTR) under mesophilic conditions. Seven hydraulic retention times (HRT)
      from 20 to 5 days were tested with the aim to evaluate the methane productivities
      and volatile solids (VS) removal. The corresponding organic loading rates (OLR)
      ranged from 4.2 to 12.8 gVS/L(reactor) d. The findings revealed that highest
      system efficiency was achieved at an OLR of 11.2 gVS/L(reactor) d (6 days-HRT)
      with a methane production rate (MPR) and volatile solids (VS) reduction of 2.91
      LCH4/L(reactor) d and 57.5%, respectively. The HRT of 5 days was found critical
      for the studied process, which leads to volatile fatty acids (VFA) accumulation
      and sharp drop in pH. However, the increase of HRT permits the recovery of
      system.

PMID- 26210142
TI  - Thermophilic anaerobic co-digestion of organic fraction of municipal solid waste
      (OFMSW) with food waste (FW): Enhancement of bio-hydrogen production.
AB  - Bio-hydrogen production from dry thermophilic anaerobic co-digestion (55 degrees
      C and 20% total solids) of organic fraction of municipal solid waste (OFMSW) and
      food waste (FW) was studied. OFMSW coming from mechanical-biological treatment
      plants (MBT plants) presents a low organic matter concentration. However, FW has
      a high organic matter content but several problems by accumulation of volatile
      fatty acids (VFAs) and system acidification. Tests were conducted using a mixture
      ratio of 80:20 (OFSMW:FW), to avoid the aforementioned problems. Different solid
      retention times (SRTs) - 6.6, 4.4, 2.4 and 1.9 days - were tested. It was noted
      that addition of food waste enhances the hydrogen production in all the SRTs
      tested. Best results were obtained at 1.9-day SRT. It was observed an increase
      from 0.64 to 2.51 L H2/L(reactor) day in hydrogen productivity when SRTs decrease
      from 6.6 to 1.9 days. However, the hydrogen yield increases slightly from 33.7 to
      38 mL H2/gVS(added).

PMID- 26210143
TI  - Application of anaerobic granular sludge for competitive biosorption of methylene
      blue and Pb(II): Fluorescence and response surface methodology.
AB  - This study assessed the biosorption of anaerobic granular sludge (AGS) and its
      capacity as a biosorbent to remove Pb(II) and methylene blue (MB) from multi
      components aqueous solution. It emerged that the biosorption data fitted well to
      the pseudo-second-order and Langmuir adsorption isotherm models in both single
      and binary systems. In competitive biosorption systems, Pb(II) and MB will
      suppress each other's biosorption capacity. Spectroscopic analysis, including
      Fourier transform infrared spectroscopy (FTIR) and fluorescence spectroscopy were
      integrated to explain this interaction. Hydroxyl and amine groups in AGS were the
      key functional groups for sorption. Three-dimensional excitation-emission matrix
      (3D-EEM) implied that two main protein-like substances were identified and
      quenched when Pb(II) or MB were present. Response surface methodology (RSM)
      confirmed that the removal efficiency of Pb(II) and MB reached its peak when the
      concentration ratios of Pb(II) and MB achieved a constant value of 1. 

PMID- 26210144
TI  - Microstructures and functional groups of Nannochloropsis sp. cells with arsenic
      adsorption and lipid accumulation.
AB  - The pore structures and surface morphological characteristics of Nannochloropsis
      sp. cells with arsenic adsorption were initially investigated by N2-adsorption
      analysis and scanning electronic microscopy. Functional groups of cells were
      analysed by Fourier-transform infrared spectrometry and X-ray photoelectron
      spectroscopy. Total surface area of microalgal cells increased from 0.54 m(2)/g
      to 1.80 m(2)/g upon arsenic adsorption. The external cell surface area increased.
      More wrinkles and measles-like granules formed on the surfaces as a result of
      arsenic toxicity. Arsenic ions blocked cell pores and decreased the average pore
      diameter and total pore volume. Ether cross-linked structures in the algaenan
      layer of cell walls were disrupted as the percentage of C-O functional groups
      decreased. These functional groups underwent complexation reactions with arsenic
      ions. Accumulation of polyunsaturated fatty acids decreased because of oxidative
      stresses induced by arsenic. The increase in generation of short-chain saturated
      fatty acids was favourable for the production of quality biodiesel.

PMID- 26210145
TI  - Pyrolysis and catalytic upgrading of Citrus unshiu peel.
AB  - Ex situ catalytic pyrolysis of Citrus unshiu (C. unshiu) peel was performed using
      a tandem MU-reactor-GC/MS consisting of two sequential furnaces. The pyrolyzates
      of C. unshiu peel, composed mainly of alcohols, ketones and furans produced in
      the 1st furnace of the reactor, were upgraded to aromatics by the use of
      catalysts in the 2nd furnace. Compared to wood powder, C. unshiu peel produced
      larger amounts of aromatics over HZSM-5(23). Among the various catalysts, HZSM
      5(23) and HBETA(25) showed high aromatic yields, 6.78 C% and 9.69 C%,
      respectively. HBETA(25) produced large amounts of undesirable PAHs (3.59 C%).
      During the sequential catalytic upgrading test, the yield of BTEXs (benzene,
      toluene, ethylbenzene, xylenes) over HZSM-5(23) was reduced more slowly than that
      over HBETA(25) because of the slower deactivation of HZSM-5(23), which suggests
      that HZSM-5(23) is a more stable catalyst than the other catalysts used in this
      study during the sequential catalytic upgrading of C. unshiu peel pyrolyzates. 

PMID- 26210146
TI  - Evaluation of biological pretreatments to increase the efficiency of the
      saccharification process using Spartina argentinensis as a biomass resource.
AB  - Second generation bioethanol obtained from native perennial grasses offers a
      promising alternative for biofuel production, avoiding land use competition for
      crops production. Spartina argentinensis is a native perennial C4 grass with high
      photosynthetic rates, well adapted to halo-hydromorphic soils, though its forage
      quality (palatability and digestibility) for livestock is quite low due to its
      high lignin content. Hence, cattle raisers burn these grasslands frequently in
      order to stimulate the emergence of new leaves with higher digestibility for
      cattle feeding. Lignin is the main barrier to overcome in order to efficiently
      hydrolyze the cellulose for bioethanol production. In this work, we evaluate
      different pretreatments (phosphoric acid, ligninolytic enzymes and fungal
      supernatants) aimed to remove lignin and improving cellulose hydrolysis
      efficiency. Results show that pretreatment with Pycnoporus sanguineus supernatant
      improves fermentable carbohydrates availability, compared with a conventional
      chemical pretreatment, and that 56.84% of cellulose can be hydrolyzed using this
      pretreatment. 

PMID- 26210147
TI  - Cultivation of Chlorella sp. GD using piggery wastewater for biomass and lipid
      production.
AB  - The development of a culture system for Chlorella sp. GD to efficiently produce
      biomass and oil for biodiesel production was investigated. Chlorella sp. GD was
      cultivated with 0%, 25%, 50%, 75% and 100% piggery wastewater (diluted by medium)
      at 300 MUmol m(-2) s(-1), a 2% CO2 aeration rate of 0.2 vvm and 26+/-1 degrees C;
      after a 10-day culture in batch cultures, the maximum specific growth rate and
      biomass productivity of the microalga obtained in 100% piggery wastewater were
      0.839 d(-1) and 0.681 g L(-1) d(-1), respectively. The highest lipid content and
      lipid productivity were 29.3% and 0.155 g L(-1) d(-1) at 25% wastewater,
      respectively. In semi-continuous cultures, the biomass and lipid productivities
      with 25-75% wastewater ratios were greater than 0.852 and 0.128 g L(-1) d(-1),
      respectively. These results show that Chlorella sp. GD grows efficiently in
      piggery wastewater, and that a stable growth performance was achieved for long
      term microalgal cultivation in a semi-continuous culture.

PMID- 26210148
TI  - Efficient production of bioactive metabolites from Antrodia camphorata ATCC
      200183 by asexual reproduction-based repeated batch fermentation.
AB  - Large-scale submerged fermentation (SmF) of Antrodia camphorata (A. camphorata)
      usually encounters challenges including tedious preparation of mycelial inoculum,
      long fermentation period (10-14 d), and poor repeatability. Here we developed an
      asexual reproduction-based repeated batch fermentation (RBF) process for
      bioactive metabolites production by A. camphorata ATCC 200183. Compared with
      traditional batch fermentation, production time was shortened to 58 d from 80 d
      (overall time for eight cycles) using the RBF process established in this study,
      and accordingly, the productivities of bioactive metabolites (including
      antrodins) were improved by 40-60%. Kinetic parameters (alpha is 2.1-18.7 times
      as beta) indicated that the cell growth was the major contribution for bioactive
      metabolites production. The RBF shows excellent batch-repeatability (Pearson
      correlation coefficient of 0.998+/-0.001), together with advantages of energy
      efficient, low cost, and labor-saving, RBF process can be implemented to SmF by
      other filamentous fungi.

PMID- 26210149
TI  - A new organic matter fractionation methodology for organic wastes:
      Bioaccessibility and complexity characterization for treatment optimization.
AB  - Organic matter characterization is the starting point to describe organic waste
      treatments mechanisms and to propose their modeling. Two relevant
      characterization methodologies were frequently used in the literature based on
      chemical extractions and fluorescence spectroscopy. However, they could not be
      generalized to all the type of wastes because of the different molecules
      targeted. Consequently, a new fractionation methodology was proposed to unify the
      characterization of a wide range of organic wastes. This new method was built by
      merging the two previously mentioned protocols to simulate bioaccessibility
      combined with 3D fluorescence spectroscopy to highlight the complexity of the
      extracted organic fractions. Sixty samples including representative samples used
      to validate the method were characterized according to their bioaccessibility and
      their complexity. Thanks to a principal component analysis, organic wastes were
      classified according to their nature, their complexity and accessibility. The
      applicability of this method in statistical or dynamic models is very promising. 

PMID- 26210150
TI  - Improvement of gaseous energy recovery from sugarcane bagasse by dark
      fermentation followed by biomethanation process.
AB  - The aim of the present study was to enhance the gaseous energy recovery from
      sugarcane bagasse. The two stage (biohydrogen and biomethanation) batch process
      was considered under mesophilic condition. Alkali pretreatment (ALP) was used to
      remove lignin from sugarcane bagasse. This enhanced the enzymatic digestibility
      of bagasse to a great extent. The maximum lignin removal of 60% w/w was achieved
      at 0.25 N NaOH concentration (50 degrees C, 30 min). The enzymatic hydrolysis
      efficiency was increased to about 2.6-folds with alkali pretreated sugarcane
      bagasse as compared to untreated one. The maximum hydrogen and methane yields
      from the treated sugarcane bagasse by biohydrogen and biomethanation processes
      were 93.4 mL/g-VS and 221.8 mL/g-VS respectively. This process resulted in
      significant increase in energy conversion efficiency (44.8%) as compared to
      single stage hydrogen production process (5.4%).

PMID- 26210151
TI  - Functional analysis of the type II toxin-antitoxin systems of the MazEF and RelBE
      families in Bifidobacterium longum subsp. infantis ATCC 15697.
AB  - Analysis of the Bifidobacterium longum subsp. infantis ATCC 15697 genome sequence
      for the presence of toxin-antitoxin genes revealed two relBE-like operons, three
      relB-mazF-like operons, one relB-vapC-like operon, one solitary gene coding for
      the MazF toxin and one gene coding for the RelB antitoxin. An attempt to clone
      the selected relE and mazF toxin genes from B. longum subsp. infantis ATCC 15697
      revealed their toxic effects on Escherichia coli, which could be neutralized by
      coexpression of these toxins with their cognate antitoxins. The only two toxin
      proteins, RelE and VapC, that were found to be non-toxic to E. coli, were
      overproduced and purified. Electrophoretic assays showed that both RelE and VapC
      possessed direct endoribonuclease activity. The expression levels of toxin genes
      in B. longum subsp. infantis ATCC 15697 increased during the nutrient starvation
      and entry into the late stationary phase. The two relBE bicistronic operons relE2
      relB1 and relE1-relB4 from B. longum subsp. infantis ATCC 15697 were cloned and
      overexpressed in B. longum subsp. longum NCC2705 strain. The strain B. longum
      NCC2705 [pCESH80::relE1-relB4] showed a significantly decreased growth rate with
      later onset of the log phase and decreased cells density in the stationary phase.

PMID- 26210154
TI  - Electrostatics of the photosynthetic bacterial reaction center. Protonation of
      Glu L 212 and Asp L 213 - A new method of calculation.
AB  - Continuum electrostatic calculation of the transfer energies of anions from water
      into aprotic solvents gives the figures erroneous by order of magnitude. This is
      due to the hydrogen bond disruption that suggests the necessity to reconsider the
      traditional approach of the purely electrostatic calculation of the transfer
      energy from water into protein. In this paper, the method combining the
      experimental estimates of the transfer energies from water into aprotic solvent
      and the electrostatic calculation of the transfer energies from aprotic solvent
      into protein is proposed. Hydrogen bonds between aprotic solvent and solute are
      taken into account by introducing an imaginary aprotic medium incapable to form
      hydrogen bonds with the solute. Besides, a new treatment of the heterogeneous
      intraprotein dielectric permittivity based on the microscopic protein structure
      and electrometric measurements is elaborated. The method accounts semi
      quantitatively for the electrostatic effect of diverse charged amino acid
      substitutions in the donor and acceptor parts of the photosynthetic bacterial
      reaction center from Rhodobacter sphaeroides. Analysis of the volatile secondary
      acceptor site QB revealed that in the conformation with a minimal distance
      between quinone QB and Glu L 212 the proton uptake upon the reduction of QB is
      prompted by Glu L 212 in alkaline and by Asp L 213 in slightly acidic regions.
      This agrees with the pH dependences of protonation degrees and the proton uptake.
      The method of pK calculation was applied successfully also for dissociation of
      Asp 26 in bacterial thioredoxin. 

PMID- 26210153
TI  - Regulation of alphaA- and alphaB-crystallins via phosphorylation in cellular
      homeostasis.
AB  - alphaA-Crystallin (alphaA) and alphaB-crystallin (alphaB) are small heat shock
      proteins responsible for the maintenance of transparency in the lens. In non
      lenticular tissues, alphaB is involved in both maintenance of the cytoskeleton
      and suppression of neurodegeneration amongst other roles. Despite their
      importance in maintaining cellular health, modifications and mutations to alphaA
      and alphaB appear to play a role in disease states such as cataract and
      myopathies. The list of modifications that have been reported is extensive and
      include oxidation, disulphide bond formation, C- and N-terminal truncation,
      acetylation, carboxymethylation, carboxyethylation, carbamylation, deamidation,
      phosphorylation and methylation. Such modifications, notably phosphorylation, are
      alleged to cause changes to chaperone activity by inducing substructural changes
      and altering subunit exchange dynamics. Although the effect modification has on
      the activities of alphaA and alphaB is contentious, it has been proposed that
      these changes are responsible for the induction of hyperactivity and are thereby
      indirectly responsible for protein deposition characteristic of many diseases
      associated with alphaA and alphaB. This review compiles all reported sites of
      alphaA and alphaB modifications, and investigates the role phosphorylation, in
      particular, plays in cellular processes.

PMID- 26210152
TI  - Macrophage polarization in pathology.
AB  - Macrophages are cells of the innate immunity constituting the mononuclear
      phagocyte system and endowed with remarkable different roles essential for
      defense mechanisms, development of tissues, and homeostasis. They derive from
      hematopoietic precursors and since the early steps of fetal life populate
      peripheral tissues, a process continuing throughout adult life. Although present
      essentially in every organ/tissue, macrophages are more abundant in the gastro
      intestinal tract, liver, spleen, upper airways, and brain. They have phagocytic
      and bactericidal activity and produce inflammatory cytokines that are important
      to drive adaptive immune responses. Macrophage functions are settled in response
      to microenvironmental signals, which drive the acquisition of polarized programs,
      whose extremes are simplified in the M1 and M2 dichotomy. Functional skewing of
      monocyte/macrophage polarization occurs in physiological conditions (e.g.,
      ontogenesis and pregnancy), as well as in pathology (allergic and chronic
      inflammation, tissue repair, infection, and cancer) and is now considered a key
      determinant of disease development and/or regression. Here, we will review
      evidence supporting a dynamic skewing of macrophage functions in disease, which
      may provide a basis for macrophage-centered therapeutic strategies.

PMID- 26210155
TI  - Are biomarkers evaluated in biopsy specimens predictive of prostate cancer
      aggressiveness?
AB  - PURPOSE: To evaluate biomarkers involved in biological pathways for prostate
      cancer (PCa) progression, measured in biopsy specimens, in order to distinguish
      patients at higher risk for fatal PCa and thus improve the initial management of
      disease. METHODS: Retrospective case-control study. In 129 PCa patients who
      underwent ultrasound-guided needle prostate biopsy and subsequent radical
      prostatectomy from 1987 to 1999 at the University Hospital of Careggi, we
      evaluated: (1) mRNA expression of the serine 2 (TMPRSS2): erythroblastosis virus
      E26 oncogene homolog (ERG); (2) expression of matrix metalloproteinases (MMP)-2
      and 9 (epithelial and stromal); (3) expression of androgen receptor; (4)
      expression of prognostic marker Ki67 (MIB1); (5) presence and typing of human
      papilloma virus; (6) DNA methylation of CpG islands of several genes involved in
      PCa progression. RESULTS: The cohort consists of 38 cases (patients with PCa and
      died of PCa within 10 years from diagnosis) and 91 controls (patients with PCa
      but alive 10 years after diagnosis). Gleason bioptic score, epithelial MMP
      expression and SERPINB5 methylation correlated with statistically significant
      increase in death risk OR. Compared with patients with high level of MMP,
      patients with low level of MMP had OR for specific death 4.78 times higher (p =
      0.0066). After adjustment for age and Gleason score, none of the investigated
      biomarkers showed increased OR for PCa death. CONCLUSIONS: Our preliminary
      results suggest that evaluation, in prostate biopsy specimens, of a panel of
      biomarkers known to be involved in PCa progression is poorly indicative of tumor
      outcome.

PMID- 26210156
TI  - Prevalence and number of circulating tumour cells and microemboli at diagnosis of
      advanced NSCLC.
AB  - PURPOSE: Timing and magnitude of blood release of circulating tumour cells (CTC)
      and circulating tumour microemboli (CTM) from primary solid cancers are
      uncertain. We investigated prevalence and number of CTC and CTM at diagnosis of
      advanced non-small cell lung cancer (NSCLC). METHODS: Twenty-eight consecutive
      patients with suspected stage III-IV lung cancer gave consent to provide 15 mL of
      peripheral blood soon before diagnostic CT-guided fine-needle aspiration biopsy
      (FNAB). CTC and CTM (clusters of >=3 CTC) were isolated by cell size filtration
      (ScreenCell), identified and counted by cytopathologists using morphometric
      criteria and (in 6 cases) immunostained for vimentin. RESULTS: FNAB demonstrated
      NSCLC in 26 cases. At least one CTC/3 mL blood (mean 6.8 +/- 3.7) was detected in
      17 (65 %) and one CTM (mean 4.5 +/- 3.3) in 15 (58 %) of 26 NSCLC cases. No
      correlation between number of CTC or CTM and tumour type or stage was observed.
      Neoplastic cells from both FNA and CTC/CTM were positive for vimentin but
      heterogeneously. CONCLUSIONS: CTC can be detected in two-thirds and CTM in more
      than half of patients with advanced NSCLC at diagnosis. Reasons underlying lack
      of CTC and CTM in some advanced lung cancers deserve further investigations.

PMID- 26210157
TI  - Purely endoscopic trans-nasal management of orbital intraconal cavernous
      haemangiomas: a systematic review of the literature.
AB  - The surgical management of medial and inferior orbital lesions is demanding via
      traditional external approach, since the conic-shaped surgical field is narrow
      and damage to neural, muscular or vascular structures of the orbit can have
      serious consequences. In recent years, the evolution of endoscopic endonasal
      approaches for lesions that goes beyond the nose brought the orbit to the
      attention of rhinosurgeons. If procedures such as transnasal orbital
      decompression and lacrimal pathways surgery have been described some decades ago,
      the last frontier of transnasal orbital surgery, namely intraconal tumor surgery,
      is a new and rapidly expanding field. Papers describing endoscopic endonasal
      approaches to the orbit appeared in the international literature, but most of
      them contain a small number of cases, also because the relatively rarity of
      intraorbital lesions. We herein report the results of a systematic review of the
      literature regarding the endoscopic endonasal approach to intraconal cavernous
      haemangiomas, the most common benign orbital lesion. The endoscopic management of
      intraconal cavernous haemangiomas results feasible and safe. A critical step of
      this kind of surgery is the management of the medial rectus muscle, mandatory to
      expose the intraconal space. 

PMID- 26210158
TI  - Novel fluorine-18 labeled 5-(1-pyrrolidinylsulfonyl)-7-azaisatin derivatives as
      potential PET tracers for in vivo imaging of activated caspases in apoptosis.
AB  - The programmed type I cell death, defined as apoptosis, is induced by complex
      regulated signaling pathways that trigger the intracellular activation of
      executioner caspases-3, -6 and -7. Once activated, these enzymes initiate
      cellular death through cleavage of proteins which are responsible for DNA repair,
      signaling and cell maintenance. Several radiofluorinated inhibitors of caspases-3
      and -7, comprising a moderate lipophilic 5-(1-pyrrolidinylsulfonyl)isatin lead
      structure, are currently being investigated for imaging apoptosis in vivo by us
      and others. The purpose of this study was to increase the intrinsic
      hydrophilicity of the aforementioned lead structure to alter the pharmacokinetic
      behavior of the resulting caspase-3 and -7 targeted radiotracer. Therefore,
      fluorinated and non-fluorinated derivatives of 5-(1-pyrrolidinylsulfonyl)-7
      azaisatin were synthesized and tested for their inhibitory properties against
      recombinant caspases-3 and -7. Fluorine-18 has been introduced by copper(I)
      catalyzed azide-alkyne cycloaddition (CuAAC) of an alkyne precursor with 2
      [(18)F]fluoroethylazide. Using dynamic micro-PET biodistribution studies in vivo
      the kinetic behavior of one promising PET-compatible 5-pyrrolidinylsulfonyl 7
      azaisatin derivative has been compared to a previously described isatin based
      radiotracer. 

PMID- 26210159
TI  - NMR-based conformational analysis of 2',6-disubstituted uridines and antiviral
      evaluation of new phosphoramidate prodrugs.
AB  - Six novel phosphoramidate prodrugs of uridine analogues, with structural
      modifications introduced at the 6- and 2',6-positions, have been prepared and
      evaluated for selective antiviral activity against hepatitis C virus, as well as
      other positive-stranded RNA viruses. An analysis of the conformational properties
      of the parent nucleosides was carried out using two-dimensional NMR spectroscopy
      based experiments, highlighting a 3'-endo (North) sugar puckering preference and
      syn orientation. 

PMID- 26210160
TI  - Identification of 2-[2-(4-tert-butylphenyl)ethyl]-N-(4-fluorophenyl)-1,2,3,4
      tetrahydroisoquinoline-6-sulfonamide (29) as an orally available MGAT2 inhibitor.
AB  - MGAT2 (monoacylglycerol acyltransferase 2) is expected to be an attractive target
      for the drug treatment of obesity, diabetes, and other disease. We describe our
      exploration and structure-activity relationship (SAR) study of 2,3-dihydro-1H
      isoindole-5-sulfonamide derivatives. In this study, we identified 29 as an orally
      available inhibitor of MGAT2 through optimization especially in terms of
      solubility. This compound exhibited moderate potency in the enzyme inhibitory
      assay (IC50 = 1522 nM) and significant suppression of fat absorption (57%
      inhibition) in mice oral lipid tolerance test.

PMID- 26210161
TI  - Modification of N-(6-(2-methoxy-3-(4-fluorophenylsulfonamido)pyridin-5-yl)
      [1,2,4]triazolo[1,5-a]pyridin-2-yl)acetamide as PI3Ks inhibitor by replacement of
      the acetamide group with alkylurea.
AB  - N-(6-(2-Methoxy-3-(4-fluorophenylsulfonamido)pyridin-5-yl)-[1,2,4]triazolo[1,5
      a]pyridin-2-yl)acetamide exhibits remarkable anticancer effects and toxicity when
      orally administrated. In present study, alkylurea moiety replaced the acetamide
      group in the compound and a series of 1-alkyl-3-(6-(2-methoxy-3
      sulfonylaminopyridin-5-yl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl)urea derivatives
      were synthesized. The antiproliferative activities of the synthesized compounds
      in vitro were evaluated against four human cancer cell lines. Several compounds
      with potent antiproliferative activities were tested for their acute oral
      toxicity and their inhibitory activity against PI3Ks and mTOR. The results
      indicate that the compound attached a alkylurea or 2-(dialkylamino)ethylurea
      moiety at the 2-position of [1,2,4]triazolo[1,5-a]pyridine can retain the
      antiproliferative activity and the inhibitory activity against PI3Ks and mTOR. In
      addition, their acute oral toxicity reduced dramatically. Moreover, the results
      also indicate that compound 1e can efficaciously inhibit tumor growth in a mice
      S180 model. These findings suggest that title compounds can serve as potent PI3K
      inhibitors and effective anticancer agents with low toxicity. 

PMID- 26210162
TI  - Assessment of adverse events via a telephone consultation service for cancer
      patients receiving ambulatory chemotherapy.
AB  - BACKGROUND: An increasing number of cancer patients are receiving ambulatory
      chemotherapy to improve their quality of life and reduce medical expenses. During
      outpatient chemotherapy, adverse events (AEs) occurring at home must be carefully
      monitored. We investigated the use of our institution's telephone consultation
      service that is available to patients and their caregivers for advice on and the
      management of AEs and complications arising from cancer treatment. PATIENTS AND
      METHODS: Telephone consultants assessed and graded AEs according to the Common
      Terminology Criteria for Adverse Events (CTCAE). All patient characteristics,
      AEs, and background factors were analyzed using logistic regression analyses.
      RESULTS: Between August 2011 and August 2012, we included 253 patients and 344
      telephone consultations regarding AEs during chemotherapy for analysis in this
      study. Grade 1 AEs were assessed in 223 consultations (65%); grade 2 AEs, in 90
      consultations (26%); and grade 3 AEs, in 31 consultations (9%). A multivariate
      logistic regression analysis revealed an association between a change in patient
      schedules and the occurrence of grade 2 or worse AEs (Hazard ratio = 6.58, P <
      0.001). Changes in planned chemotherapy occurred more often in cases involving
      male patients (Hazard ratio = 2.70, P = 0.02) and in cases of grade 2 or worse
      AEs (Hazard ratio = 6.58, P < 0.001). CONCLUSION: We found that AE assessment
      using CTCAE via a telephone consultation service is useful for both the triage of
      patients and the prediction of severe AEs that may change clinical schedules.

PMID- 26210164
TI  - Proteobacteria: microbial signature of dysbiosis in gut microbiota.
AB  - Recent advances in sequencing techniques, applied to the study of microbial
      communities, have provided compelling evidence that the mammalian intestinal
      tract harbors a complex microbial community whose composition is a critical
      determinant of host health in the context of metabolism and inflammation. Given
      that an imbalanced gut microbiota often arises from a sustained increase in
      abundance of the phylum Proteobacteria, the natural human gut flora normally
      contains only a minor proportion of this phylum. Here, we review studies that
      explored the association between an abnormal expansion of Proteobacteria and a
      compromised ability to maintain a balanced gut microbial community. We also
      propose that an increased prevalence of Proteobacteria is a potential diagnostic
      signature of dysbiosis and risk of disease. 

PMID- 26210163
TI  - Removing reference mapping biases using limited or no genotype data identifies
      allelic differences in protein binding at disease-associated loci.
AB  - BACKGROUND: Genetic variation can alter transcriptional regulatory activity
      contributing to variation in complex traits and risk of disease, but identifying
      individual variants that affect regulatory activity has been challenging.
      Quantitative sequence-based experiments such as ChIP-seq and DNase-seq can detect
      sites of allelic imbalance where alleles contribute disproportionately to the
      overall signal suggesting allelic differences in regulatory activity. METHODS: We
      created an allelic imbalance detection pipeline, AA-ALIGNER, to remove reference
      mapping biases influencing allelic imbalance detection and evaluate accuracy of
      allelic imbalance predictions in the absence of complete genotype data. Using the
      sequence aligner, GSNAP, and varying amounts of genotype information to remove
      mapping biases we investigated the accuracy of allelic imbalance detection
      (binomial test) in CREB1 ChIP-seq reads from the GM12878 cell line. Additionally
      we thoroughly evaluated the influence of experimental and analytical parameters
      on imbalance detection. RESULTS: Compared to imbalances identified using complete
      genotypes, using imputed partial sample genotypes, AA-ALIGNER detected >95 % of
      imbalances with >90 % accuracy. AA-ALIGNER performed nearly as well using common
      variants when genotypes were unknown. In contrast, predicting additional
      heterozygous sites and imbalances using the sequence data led to >50 % false
      positive rates. We evaluated effects of experimental data characteristics and key
      analytical parameter settings on imbalance detection. Overall, total base
      coverage and signal dispersion across the genome most affected our ability to
      detect imbalances, while parameters such as imbalance significance, imputation
      quality thresholds, and alignment mismatches had little effect. To assess the
      biological relevance of imbalance predictions, we used electrophoretic mobility
      shift assays to functionally test for predicted allelic differences in CREB1
      binding in the GM12878 lymphoblast cell line. Six of nine tested variants
      exhibited allelic differences in binding. Two of these variants, rs2382818 and
      rs713875, are located within inflammatory bowel disease-associated loci.
      CONCLUSIONS: AA-ALIGNER accurately detects allelic imbalance in quantitative
      sequence data using partial genotypes or common variants filling a critical
      methodological gap in these analyses, as full genotypes are rarely available.
      Importantly, we demonstrate how experimental and analytical features impact
      imbalance detection providing guidance for similar future studies.

PMID- 26210165
TI  - Concentration of fractional excretion of nitric oxide (FENO): A potential airway
      biomarker of restored CFTR function.
AB  - BACKGROUND: Lower airway biomarkers of restored cystic fibrosis transmembrane
      conductance regulator (CFTR) function are limited. We hypothesized that
      fractional excretion of nitric oxide (FENO), typically low in CF patients, would
      demonstrate reproducibility during CFTR-independent therapies, and increase
      during CFTR-specific intervention (ivacaftor) in patients with CFTR gating
      mutations. METHODS: Repeated FENO and spirometry measurements in children with CF
      (Cohort 1; n=29) were performed during hospital admission for acute pulmonary
      exacerbations and routine outpatient care. FENO measurements before and after one
      month of ivacaftor treatment (150 mg every 12h) were completed in CF patients
      with CFTR gating mutations (Cohort 2; n=5). RESULTS: Cohort 1: Mean forced
      expiratory volume in 1s (FEV1 % predicted) at enrollment was 72.3% (range 25%
      102%). Mean FENO measurements varied minimally over the two inpatient and two
      outpatient measurements (9.8-10.9 ppb). There were no clear changes related to
      treatment of pulmonary exacerbations, gender, genotype or microbiology, and weak
      correlation with inhaled corticosteroid use (P<0.05). Between the two inpatient
      measurements, FEV1 % predicted increased by 7.3% (P<0.03) and FENO did not
      change. In Cohort 2, mean FENO increased from 6.6 ppb (SD=2.19) to 11.8 ppb
      (SD=4.97) during ivacaftor treatment. Mean sweat chloride dropped by 58 mM and
      mean FEV1 % predicted increased by 10.2%. CONCLUSIONS: Repeated FENO measurements
      were stable in CF patients, whereas FENO increased in all patients with CFTR
      gating mutations treated with ivacaftor. Acute changes in FENO may serve as a
      biomarker of restored CFTR function in the CF lower airway during CFTR modulator
      treatment.

PMID- 26210166
TI  - The effects of intravenous fosaprepitant and ondansetron in the prevention of
      postoperative nausea and vomiting in patients who underwent lower limb surgery: a
      prospective, randomized, double-blind study.
AB  - PURPOSE: Postoperative nausea and vomiting (PONV) is the most common complication
      after surgery, and opioid administration increases its incidence. We compared the
      preventive effects of fosaprepitant, a neurokinin-1 (NK1) receptor antagonist,
      with those of ondansetron on PONV in patients who underwent lower limb surgery
      with postoperative epidural opioid administration. METHODS: This prospective,
      double-blind, randomized study included 38 patients who underwent lower limb
      surgery. They were randomly allocated to receive intravenous fosaprepitant 150 mg
      (n = 19; NK1 group) or ondansetron 4 mg (n = 19; ONS group) before general
      anesthesia. All patients received postoperative epidural fentanyl for pain
      control. The incidence of nausea and vomiting, complete response rate (no
      vomiting and no rescue antiemetic use), rescue antiemetic use, nausea score (0
      3), and visual analog scale (VAS 0-10) score for pain were recorded at 2, 24, and
      48 h after surgery. RESULTS: No patient in the NK1 group experienced vomiting
      (0%) during the first 24 and 48 h after surgery, while 5 of 19 (26%) patients in
      the ONS group experienced this complication, indicating a significant difference
      between groups. There were no significant differences in the incidence of PONV,
      complete response rate, rescue antiemetic use, nausea score, and VAS score for
      pain between the NK1 and ONS groups during the study period. CONCLUSIONS:
      Fosaprepitant was more effective than ondansetron in decreasing the incidence of
      vomiting after lower limb surgery with postoperative opioid administration.
      Meanwhile, fosaprepitant was not inferior to ondansetron in decreasing the
      incidence and severity of PONV.

PMID- 26210167
TI  - 'The government cannot do it all alone': realist analysis of the minutes of
      community health committee meetings in Nigeria.
AB  - Since the mid-1980s, the national health policy in Nigeria has sought to inspire
      community engagement in primary health care by bringing communities into
      partnership with service providers through community health committees. Using a
      realist approach to understand how and under what circumstances the committees
      function, we explored 581 meeting minutes from 129 committees across four states
      in Nigeria (Lagos, Benue, Nasarawa and Kaduna). We found that community health
      committees provide opportunities for improving the demand and supply of health
      care in their community. Committees demonstrate five modes of functioning:
      through meetings (as 'village square'), reaching out within their community (as
      'community connectors'), lobbying governments for support (as 'government
      botherers'), inducing and augmenting government support (as 'back-up government')
      and taking control of health care in their community (as 'general overseers'). In
      performing these functions, community health committees operate within and
      through the existing social, cultural and religious structures of their
      community, thereby providing an opportunity for the health facility with which
      they are linked to be responsive to the needs and values of the community. But
      due to power asymmetries, committees have limited capacity to influence health
      facilities for improved performance, and governments for improved health service
      provision. This is perhaps because national guidelines are not clear on their
      accountability functions; they are not aware of the minimum standards of services
      to expect; and they have a limited sense of legitimacy in their relations with
      sub-national governments because they are established as the consequence of a
      national policy. Committees therefore tend to promote collective action for self
      support more than collective action for demanding accountability. To function
      optimally, community health committees require national government or non
      government organization mentoring and support; they need to be enshrined in law
      to bolster their sense of legitimacy; and they also require financial support to
      subsidise their operation costs especially in geographically large communities. 

PMID- 26210169
TI  - Diagnostics of temporomandibular disorder: the good, the bad and the ugly.

PMID- 26210168
TI  - Maxillary pseudotumor as initial manifestation of von Willebrand disease, type 2:
      report of a rare case and literature review.
AB  - OBJECTIVES: Von Willebrand disease (VWD) is a bleeding disorder associated with
      inherited defects of von Willebrand factor (VWF). Type 2 N VWD is characterized
      by impaired FVIII-binding capacity (VWF:FVIIIB). Pseudotumor (PT) represents a
      serious complication of hemophilia. Case reports of oral PTs in VWD remain
      scarce. METHODS: An 11-year-old Caucasian female presented with an expansile
      gingival mass of the posterior maxilla. Surgical excision of the tumor was
      performed. RESULTS: Histopathologically, the tumor was characterized by cystic
      spaces filled with hemorrhagic material and dense fibrous connective tissue.
      Postoperatively, the patient suffered prolonged hemorrhage. Results of blood
      tests showed decreased levels of FVIII function ( FVIII: C) and VWF:FVIIIB.
      Subsequent gene analysis for type 2 N VWD confirmed heterozygosity for the
      missense mutation p.Arg816 Trp. A diagnosis of oral PT was rendered. CONCLUSIONS:
      Here, we report the clinical, radiographic, and microscopic features of a rare
      example of oral PT leading to the diagnosis of type 2 N VWD.

PMID- 26210170
TI  - In vitro study on proliferation kinetics of oral mucosal keratinocytes.
AB  - OBJECTIVE: The limited availability of autogenous oral mucosa in oral and
      maxillofacial surgery for intraoral grafting after trauma or tumor resection can
      be balanced by the use of tissue-engineered oral mucosa. However, the use of
      tissue engineering in autologous grafts is still subject to further research. The
      aim of this study was to evaluate conditions that lead to a rapid proliferation
      of vital and highly proliferative oral keratinocytes, which can be used in tissue
      engineering and consequently help improve surgical management of intraoral
      mucosal defects. MATERIAL AND METHODS: Human oral keratinocytes were obtained
      from oral mucosal specimens and cultivated. According to their affinity to beta1
      integrin, epidermal stem cell populations were isolated by using collagen type IV
      and laminin-coated dishes. Cell proliferation and cell viability were measured by
      using the CASY cell counter, WST-1 assays, and real-time cell analysis
      (xCELLigence). RESULTS: Measurements on cell proliferation (CASY cell counter)
      and cell viability (WST-1 assay) showed the characteristic proliferation stages
      of in vitro-cultivated cells. No statistically significant differences could be
      monitored (P > .05). Real-time cell analysis, as a more direct and precise
      technique, revealed a steeper growth curve of adherent cells and therefore
      generally higher proliferation kinetics compared with cells derived from the
      supernate. CONCLUSION: Data from real-time cell analysis showed an increased
      proliferation of adherent cells compared with those derived from the supernate.
      These results demonstrate the increase of the proliferation capacity by
      cultivation of keratinocytes derived by adhesion to extracellular matrix
      proteins.

PMID- 26210171
TI  - Negative electrospray ionization mode in mass spectrometry: A new perspective via
      modeling.
AB  - Electrospray ionization technique is used for production of gas phase ions
      without fragmentation and is considered as one of the most sensitive analytical
      methods for structural characterization of molecules. Nonetheless, the
      determination of some parameters (physicochemical properties or structural
      features) that may enhance the signal response especially in the negative ion
      mode has not yet been clarified. The present work is an attempt to correlate the
      signal response behavior of 110 compounds used as probes, with their
      characteristics (molecular descriptors, X variables). In order to quantify this
      phenomenon, Partial Least Squares which is a software capable of performing
      linear multivariate analysis was applied. The models derived explore the positive
      or negative effect of 49 X variables on the signal response of each analyte,
      expressed as Y variable. The process of gas phase ions formation was verified by
      both flow injection and column analysis. The models derived are proven reliable
      for the study of such mechanisms, with small number of components and good
      linearity (R(2)>83%, Q(2)>70%). The present study showed that parameters as pKa,
      ionization percentage of the analyte, PSA, HBA, COOH, water solubility and
      surface tension of a solid are affecting ion formation. At the same time, slight
      differentiations of the influence of certain parameters were observed on column
      injection analysis due to the chromatographic delay of some analytes. 

PMID- 26210172
TI  - Vascular endothelial growth factor signaling affects both angiogenesis and
      osteogenesis during the development of scleral ossicles.
AB  - Intramembranous ossification is a complex multi-step process which relies on
      extensive interactions among bone cells and surrounding tissues. The embryonic
      vasculature is essential in regulating endochondral ossification; however, its
      role during intramembranous ossification remains poorly understood, and in vivo
      studies are lacking. Previous research from our lab on the development of the
      intramembranous scleral ossicles has demonstrated an intriguing pattern of
      vascular development in which the areas of future osteogenesis remain avascular
      until after bone induction has occurred. Such avascular zones are located
      directly beneath each of the conjunctival papillae, epithelial structures which
      provide osteogenic signals to the underlying mesenchyme. Here we provide a high
      resolution map of the developing vasculature from the time of ossicle induction
      to mineralization using a novel technique. We show that vegfa is expressed by the
      papillae and nearby mesenchymal tissue throughout HH 34-37, when vascular growth
      is taking place, and is down-regulated thereafter. Localized inhibition of Vegf
      results in expansion of the avascular zone surrounding the implanted papilla and
      mispatterning of the scleral ossicles. These results demonstrate that Vegf
      signaling could provide important insights into the complex relationship between
      bone and vasculature during intramembranous bone development. 

PMID- 26210173
TI  - The double capsules in macro-textured breast implants.
AB  - Breast implants are amongst the most widely used types of permanent implants in
      modern medicine and have both aesthetic and reconstructive applications with
      excellent biocompatibility. The double capsule is a complication associated with
      textured prostheses that leads to implant displacement; however, its etiology has
      yet to be elucidated. In this study, 10 double capsules were sampled from breast
      expander implants for in-depth analysis; histologically, the inner capsular layer
      demonstrated highly organized collagen in sheets with delamination of fibers. At
      the prosthesis interface (PI) where the implant shell contacts the inner capsular
      layer, scanning electron microscopy (SEM) revealed a thin layer which mirrored
      the three-dimensional characteristics of the implant texture; the external
      surface of the inner capsular layer facing the intercapsular space (ICS) was
      flat. SEM examination of the inner capsule layer revealed both a large bacterial
      presence as well as biofilm deposition at the PI; a significantly lower quantity
      of bacteria and biofilm were found at the ICS interface. These findings suggest
      that the double capsule phenomenon's etiopathogenesis is of mechanical origin.
      Delamination of the periprosthetic capsule leads to the creation of the ICS; the
      maintained separation of the 2 layers subsequently alters the biostability of the
      macro-textured breast implant. 

PMID- 26210174
TI  - Synthetic 3D diamond-based electrodes for flexible retinal neuroprostheses:
      Model, production and in vivo biocompatibility.
AB  - Two retinal implants have recently received the CE mark and one has obtained FDA
      approval for the restoration of useful vision in blind patients. Since the
      spatial resolution of current vision prostheses is not sufficient for most
      patients to detect faces or perform activities of daily living, more electrodes
      with less crosstalk are needed to transfer complex images to the retina. In this
      study, we modelled planar and three-dimensional (3D) implants with a distant
      ground or a ground grid, to demonstrate greater spatial resolution with 3D
      structures. Using such flexible 3D implant prototypes, we showed that the
      degenerated retina could mould itself to the inside of the wells, thereby
      isolating bipolar neurons for specific, independent stimulation. To investigate
      the in vivo biocompatibility of diamond as an electrode or an isolating material,
      we developed a procedure for depositing diamond onto flexible 3D retinal
      implants. Taking polyimide 3D implants as a reference, we compared the number of
      neurones integrating the 3D diamond structures and their ratio to the numbers of
      all cells, including glial cells. Bipolar neurones were increased whereas there
      was no increase even a decrease in the total cell number. SEM examinations of
      implants confirmed the stability of the diamond after its implantation in vivo.
      This study further demonstrates the potential of 3D designs for increasing the
      resolution of retinal implants and validates the safety of diamond materials for
      retinal implants and neuroprostheses in general. 

PMID- 26210176
TI  - Textured and hierarchically structured calcium phosphate ceramic blocks through
      hydrothermal treatment.
AB  - Synthetic calcium phosphate bone graft substitutes are widely recognized for
      their biocompatibility and resorption characteristics in the treatment of large
      bone defects. However, due to their inherent brittleness, applications in load
      bearing situations always require reinforcement by additional metallic implants.
      Improved mechanical stability would eliminate the need for non-resorbable
      metallic implants. In this context a new approach to obtain calcium phosphate
      scaffolds with improved mechanical stability by texturing the material in
      specific crystal orientations was evaluated. Texture and reduction of crystal
      size was achieved by recrystallizing alpha-TCP blocks into calcium deficient
      hydroxyapatite (CDHA) under hydrothermal conditions. SEM and XRD analysis
      revealed the formation of fine CDHA needles (diameter ~ 0.1-0.5 MUm), aligned
      over several hundreds of micrometers. The obtained microstructures were
      remarkably similar to the microstructures of the prismatic layer of mollusk
      shells or enamel, also showing organization at 5 hierarchical structure levels.
      Brazilian disc tests were used to determine the diametral tensile strength,
      sigmadts, and the work-of-fracture, WOF, of the textured materials. Hydrothermal
      incubation significantly increased sigmadts and WOF of the ceramic blocks as
      compared to sintered blocks. These improvements were attributed to the fine and
      entangled crystal structure obtained after incubation, which reduces the size of
      strength-determining critical defects and also leads to tortuous crack
      propagation. Rupture surfaces revealed intergranular tortuous crack paths, which
      dissipate much more energy than transgranular cracks as observed in the sintered
      samples. Hence, the refined and textured microstructure achieved through the
      proposed processing route is an effective way to improve the strength and
      particularly the toughness of calcium phosphate-based ceramics. 

PMID- 26210175
TI  - Effect of UV-photofunctionalization on oral bacterial attachment and biofilm
      formation to titanium implant material.
AB  - Bacterial biofilm infections remain prevalent reasons for implant failure. Dental
      implant placement occurs in the oral environment, which harbors a plethora of
      biofilm-forming bacteria. Due to its trans-mucosal placement, part of the implant
      structure is exposed to oral cavity and there is no effective measure to prevent
      bacterial attachment to implant materials. Here, we demonstrated that UV
      treatment of titanium immediately prior to use (photofunctionalization) affects
      the ability of human polymicrobial oral biofilm communities to colonize in the
      presence of salivary and blood components. UV-treatment of machined titanium
      transformed the surface from hydrophobic to superhydrophilic. UV-treated surfaces
      exhibited a significant reduction in bacterial attachment as well as subsequent
      biofilm formation compared to untreated ones, even though overall bacterial
      viability was not affected. The function of reducing bacterial colonization was
      maintained on UV-treated titanium that had been stored in a liquid environment
      before use. Denaturing gradient gel-electrophoresis (DGGE) and DNA sequencing
      analyses revealed that while bacterial community profiles appeared different
      between UV-treated and untreated titanium in the initial attachment phase, this
      difference vanished as biofilm formation progressed. Our findings confirm that UV
      photofunctionalization of titanium has a strong potential to improve outcome of
      implant placement by creating and maintaining antimicrobial surfaces. 

PMID- 26210177
TI  - Effective co-delivery of doxorubicin and dasatinib using a PEG-Fmoc nanocarrier
      for combination cancer chemotherapy.
AB  - A simple PEGylated peptidic nanocarrier, PEG5000-lysyl-(alpha-Fmoc-epsilon-Cbz
      lysine)2 (PLFCL), was developed for effective co-delivery of doxorubicin (DOX)
      and dasatinib (DAS) for combination chemotherapy. Significant synergy of DOX and
      DAS in inhibition of cancer cell proliferation was demonstrated in various types
      of cancer cells, including breast, prostate, and colon cancers. Co-encapsulation
      of the two agents was facilitated by incorporation of 9-Fluorenylmethoxycarbonyl
      (Fmoc) and carboxybenzyl (Cbz) groups into a nanocarrier for effective carrier
      drug interactions. Spherical nanomicelles with a small size of ~30 nm were self
      assembled by PLFCL. Strong carrier/drug intermolecular pi-pi stacking was
      demonstrated in fluorescence quenching and UV absorption. Fluorescence study
      showed more effective accumulation of DOX in nuclei of cancer cells following
      treatment with DOX&DAS/PLFCL in comparison with cells treated with DOX/PLFCL.
      DOX&DAS/PLFCL micelles were also more effective than other treatments in
      inhibiting the proliferation and migration of cultured cancer cells. Finally, a
      superior anti-tumor activity was demonstrated with DOX&DAS/PLFCL. A tumor growth
      inhibition rate of 95% was achieved at a respective dose of 5 mg/kg for DOX and
      DAS in a murine breast cancer model. Our nanocarrier may represent a simple and
      effective system that could facilitate clinical translation of this promising
      multi-agent regimen in combination chemotherapy. 

PMID- 26210178
TI  - Laser fabricated discontinuous anisotropic microconical substrates as a new model
      scaffold to control the directionality of neuronal network outgrowth.
AB  - Patterning of neuronal outgrowth in vitro is important in tissue engineering as
      well as for the development of neuronal interfaces with desirable
      characteristics. To date, this has been achieved with the aid of micro- and
      nanofabrication techniques giving rise to various anisotropic topographies,
      either in the form of continuous or discontinuous structures. In this study we
      propose a currently unexplored geometry of a 3D culture substrate for neuronal
      cell growth comprising discontinuous subcellular microstructures with anisotropic
      geometrical cross-section. Specifically, using laser precision 3D micro/nano
      fabrication techniques, silicon substrates comprising arrays of parallel oriented
      elliptical microcones (MCs) were fabricated to investigate whether a
      discontinuous geometry comprising anisotropic features at the subcellular level
      could influence the alignment of peripheral nervous system cell populations. It
      was shown that both Schwann cells and axons of sympathetic neurons were parallel
      oriented onto the MCs of elliptical shape, while they exhibited a random
      orientation onto the MCs of arbitrary shape. Notably, this topography-induced
      guidance effect was also observed in more complex cell culture systems, such as
      the organotypic culture whole dorsal root ganglia (DRG) explants. Our results
      suggest that a discontinuous topographical pattern could promote Schwann cell and
      axonal alignment, provided that it hosts anisotropic geometrical features, even
      though the sizes of those range at the subcellular lengthscale. The laser
      patterned arrays of MCs presented here could potentially be a useful platform for
      patterning neurons into artificial networks, allowing the study of neuronal cells
      interactions under 3D ex-vivo conditions. 

PMID- 26210179
TI  - Cell shape dependent regulation of nuclear morphology.
AB  - Recent studies suggest that actin filaments are essential in how a cell controls
      its nuclear shape. However, little is known about the relative importance of
      membrane tension in determining nuclear morphology. In this study, we used
      adhesive micropatterned substrates to alter the cellular geometry (aspect ratio,
      size, and shape) that allowed direct membrane tension or without membrane lateral
      contact with the nucleus and investigate nuclear shape remodeling and orientation
      on a series of rectangular shapes. Here we showed that at low cell aspect ratios
      the orientation of the nucleus was regulated by actin filaments while cells with
      high aspect ratios can maintain nuclear shape and orientation even when actin
      polymerization was blocked. A model adenocarcinoma cell showed similar behavior
      in the regulation of nuclear shape in response to changes in cell shape but actin
      filaments were essential in maintaining cell shape. Our results highlight the two
      distinct mechanisms to regulate nuclear shape through cell shape control and the
      difference between fibroblasts and a model cancerous cell in cell adhesion and
      cell shape control. 

PMID- 26210180
TI  - Regulation of vascular smooth muscle cell autophagy by DNA nanotube-conjugated
      mTOR siRNA.
AB  - The efficient delivery of short interfering RNA (siRNA) is an enormous challenge
      in the field of gene therapy. Herein, we report a delivery nanosystem based on
      programmed DNA self-assembly mammalian target of rapamycin (mTOR) siRNA-loaded
      DNA nanotubes (DNA-NTs). We demonstrate that these siRNA-DNA-NTs can be
      effectively transfected into pulmonary arterial smooth muscle cells (PASMCs) via
      endocytosis; and that the loaded mTOR siRNA can induce obvious autophagy and
      inhibit cell growth under both normal and hypoxic conditions. Moreover, we found
      that mTOR siRNA can control the autophagy and proliferation of PASMCs under
      hypoxic condition, suggesting a potential therapeutic application for mTOR siRNA
      in diseases involving abnormal autophagy in PASMCs. 

PMID- 26210181
TI  - Fibrinogen matrix deposited on the surface of biomaterials acts as a natural anti
      adhesive coating.
AB  - Adsorption of fibrinogen on the luminal surface of biomaterials is a critical
      early event during the interaction of blood with implanted vascular graft
      prostheses which determines their thrombogenicity. We have recently identified a
      nanoscale process by which fibrinogen modifies the adhesive properties of various
      surfaces for platelets and leukocytes. In particular, adsorption of fibrinogen at
      low density promotes cell adhesion while its adsorption at high density results
      in the formation of an extensible multilayer matrix, which dramatically reduces
      cell adhesion. It remains unknown whether deposition of fibrinogen on the surface
      of vascular graft materials produces this anti-adhesive effect. Using atomic
      force spectroscopy, single cell force spectroscopy, and standard adhesion assays
      with platelets and leukocytes, we have characterized the adhesive and physical
      properties of the contemporary biomaterials, before and after coating with
      fibrinogen. We found that uncoated PET, PTFE and ePTFE exhibited high adhesion
      forces developed between the AFM tip or cells and the surfaces. Adsorption of
      fibrinogen at the increasing concentrations progressively reduced adhesion
      forces, and at >=2 MUg/ml all surfaces were virtually nonadhesive. Standard
      adhesion assays performed with platelets and leukocytes confirmed this
      dependence. These results provide a better understanding of the molecular events
      underlying thrombogenicity of vascular grafts. 

PMID- 26210182
TI  - Dysfunction in macrophage toll-like receptor signaling caused by an inborn error
      of cationic amino acid transport.
AB  - Amino acids, especially arginine, are vital for the well-being and activity of
      immune cells, and disruption of amino acid balance may weaken immunity and
      predispose to infectious and autoimmune diseases. We present here a model of an
      inborn aminoaciduria, lysinuric protein intolerance (LPI), in which a single
      mutation in y(+)LAT1 cationic amino acid transporter gene SLC7A7 leads to a
      multisystem disease characterized by immunological complications, life
      threatening pulmonary alveolar proteinosis and nephropathy. Macrophages are
      suggested to play a central role in LPI in the development of these severe
      secondary symptoms. We thus studied the effect of the Finnish y(+)LAT1 mutation
      on monocyte-derived macrophages where toll-like receptors (TLRs) act as the key
      molecules in innate immune response against external pathogens. The function of
      LPI patient and control macrophage TLR signaling was examined by stimulating the
      TLR2/1, TLR4 and TLR9 pathways with their associated pathogen-associated
      molecular patterns. Downregulation in expression of TLR9, IRF7, IRF3 and IFNB1
      and in secretion of IFN-alpha was detected, suggesting an impaired response to
      TLR9 stimulation. In addition, secretion of TNF-alpha, IL-12 and IL-1RA by TLR2/1
      stimulation and IL-12 and IL-1RA by TLR4 stimulation was increased in the LPI
      patients. LPI macrophages secreted significantly less nitric oxide than control
      macrophages, whereas plasma concentrations of inflammatory chemokines CXCL8,
      CXCL9 and CXCL10 were elevated in the LPI patients. In conclusion, our results
      strengthen the relevance of macrophages in the pathogenesis of LPI and,
      furthermore, suggest that cationic amino acid transport plays an important role
      in the regulation of innate immune responses. 

PMID- 26210184
TI  - Roles of small RNAs in the immune defense mechanisms of crustaceans.
AB  - Small RNAs, 21-24 nucleotides in length, are non-coding RNAs found in most
      multicellular organisms, as well as in some viruses. There are three main types
      of small RNAs including microRNA (miRNA), small-interfering RNA (siRNA), and piwi
      interacting RNA (piRNA). Small RNAs play key roles in the genetic regulation of
      eukaryotes; at least 50% of all eukaryote genes are the targets of small RNAs. In
      recent years, studies have shown that some unique small RNAs are involved in the
      immune response of crustaceans, leading to lower or higher immune responses to
      infections and diseases. SiRNAs could be used as therapy for virus infection. In
      this review, we provide an overview of the diverse roles of small RNAs in the
      immune defense mechanisms of crustaceans. 

PMID- 26210183
TI  - Identifying the ERAD ubiquitin E3 ligases for viral and cellular targeting of MHC
      class I.
AB  - The human cytomegalovirus (HCMV) US2 and US11 gene products hijack mammalian ER
      associated degradation (ERAD) to induce rapid degradation of major
      histocompatibility class I (MHC-I) molecules. The rate-limiting step in this
      pathway is thought to be the polyubiquitination of MHC-I by distinct host ERAD E3
      ubiquitin ligases. TRC8 was identified as the ligase responsible for US2-mediated
      MHC-I degradation and shown to be required for the cleavage-dependent degradation
      of some tail-anchored proteins. In addition to MHC-I, plasma membrane profiling
      identified further immune receptors, which are also substrates for the US2/TRC8
      complex. These include at least six alpha integrins, the coagulation factor
      thrombomodulin and the NK cell ligand CD112. US2's use of specific HCMV-encoded
      adaptors makes it an adaptable viral degradation hub. US11-mediated degradation
      is MHC-I-specific and genetic screens have identified TMEM129, an uncharacterised
      RING-C2 E3 ligase, as responsible for US11-mediated degradation. In a unique auto
      regulatory loop, US11 readily responds to changes in cellular expression of MHC
      I. Free US11 either rebinds more MHC-I or is itself degraded by the HRD1/SEL1L E3
      ligase complex. While virally encoded US2 and US11 appropriate mammalian ERAD,
      the MHC-I complex also undergoes stringent cellular quality control and misfolded
      MHC-I is degraded by the HRD1/SEL1L complex. We discuss the identification and
      central role of E3 ubiquitin ligases in ER quality control and viral degradation
      of the MHC-I chain. 

PMID- 26210185
TI  - Identifying potential endocrine disruptors among industrial chemicals and their
      metabolites--development and evaluation of in silico tools.
AB  - The aim of this study was to improve the identification of endocrine disrupting
      chemicals (EDCs) by developing and evaluating in silico tools that predict
      interactions at the estrogen (E) and androgen (A) receptors, and binding to
      transthyretin (T). In particular, the study focuses on evaluating the use of the
      EAT models in combination with a metabolism simulator to study the significance
      of bioactivation for endocrine disruption. Balanced accuracies of the EAT models
      ranged from 77-87%, 62-77%, and 65-89% for E-, A-, and T-binding respectively.
      The developed models were applied on a set of more than 6000 commonly used
      industrial chemicals of which 9% were predicted E- and/or A-binders and 1% were
      predicted T-binders. The numbers of E- and T-binders increased 2- and 3-fold,
      respectively, after metabolic transformation, while the number of A-binders
      marginally changed. In-depth validation confirmed that several of the predicted
      bioactivated E- or T-binders demonstrated in vivo estrogenic activity or
      influenced blood levels of thyroxine in vivo. The metabolite simulator was
      evaluated using in vivo data from the literature which showed a 50% accuracy for
      studied chemicals. The study stresses, in summary, the importance of including
      metabolic activation in prioritization activities of potentially emerging
      contaminants.

PMID- 26210186
TI  - Effect of fumigation with 1,3-dichloropropene on soil bacterial communities.
AB  - 1,3-Dichloropropene (1,3-D) is a potential candidate as a soil fumigant because
      of the restriction of methyl bromide (MB) in soil fumigation. So far, little is
      known about the bacteria diversity in 1,3-D fumigated soil. Therefore, the impact
      of 1,3-D on soil bacterial community was determined by the 16S rRNA gene amplicon
      454 sequencing. A total of 230,617 valid reads and 19,366 OTUs were obtained from
      the thirteen samples. 454 sequencing results revealed that Proteobacteria,
      Bacteroidetes, Actinobacteria, Acidobacteria and Firmicutes were predominant
      phylum in soils. Bacterial diversity was affected initially, while recovered in
      the later treatments and soils from 1,3-D treatment plots had a higher bacterial
      diversity. The results of this study demonstrated that 1,3-D had only a short
      term and transitory impact on the indigenous soil microbial community. Our study
      would provide useful information for evaluating ecological safety of 1,3-D in
      China.

PMID- 26210187
TI  - Development of an embryotoxicity test for Enchytraeus crypticus--the effect of
      Cd.
AB  - The existing standard enchytraeid reproduction test (ERT) concerns the assessment
      of effects on survival and reproduction. In the present study we optimized and
      propose an embryotoxicity test using Enchytraeus crypticus. Cadmium (Cd) was used
      as a test substance. Endpoints evaluated were embryo development, number of
      embryonic structures, Calcium (Ca) channels quantification and hatching success
      with macroscopic monitoring, histological and immunohistochemistry analysis.
      Results showed that Cd is embryotoxic for this species, causing a decrease in the
      hatching success (EC50=3.1mg/kg), a delay or disruption in formation of embryonic
      structures depending on concentrations (<5mg Cd/kg or ?16mg Cd/kg). Results from
      immunohistochemistry suggest a competitive binding between Cd and Ca for Ca
      channels, resulting in changes in Ca homeostasis. The use of the E. crypticus
      embryotoxicity test with the combination of histological and immunohistological
      tools provided a good option towards mechanistic information enhancing the
      importance of these tests to evaluate the hazard of chemicals and possible use in
      risk assessment.

PMID- 26210188
TI  - Impact of soil characteristics on relative bioavailability of NDL-PCBs in
      piglets.
AB  - Children may be orally exposed to organic pollutants through involuntary soil
      ingestion. This study was aimed at determining the impact of the characteristics
      (organic carbon (OC), black carbon (BC), clay contents and pH) of ten
      contaminated soils on the bioavailability of non-dioxin-like polychlorobiphenyls
      (NDL-PCBs). Five juvenile male piglets were exposed to increasing amounts of each
      of the soils. These soil-fed groups were compared by a relative bioavailability
      approach (RBA) to a reference group fed with corn oil spiked with increasing
      doses of Aroclor 1254. After 10days of oral exposure, the animals were sacrificed
      and NDL-PCB concentrations were determined by GC-MS in the adipose tissue. The
      relative bioavailability (RBA) factors were calculated for PCB 101, 138, 153 and
      180. Despite high variations in the amount of black carbon (0.50gkg(-1)-6.0gkg(
      1)d.w.) and organic matter (12gkg(-1)-180gkg(-1)d.w.), only 3 soils exhibited a
      significantly lower RBA for all NDL-PCBs, compared to the oil-group. High levels
      of OC (>100gkg(-1)) and BC content (3.0gkg(-1)) were related to a significant
      reduction in RBA. Overall, RBA was higher than 45% independently of the soil and
      the PCB congener.

PMID- 26210189
TI  - Effects of nitrate on metamorphosis, thyroid and iodothyronine deiodinases
      expression in Bufo gargarizans larvae.
AB  - Chinese toad (Bufo gargarizans) tadpoles were exposed to nitrate (10, 50 and
      100mg/L NO3-N) from the beginning of the larval period through metamorphic
      climax. We examined the effects of chronic nitrate exposure on metamorphosis,
      mortality, body size and thyroid gland. In addition, thyroid hormone (TH) levels,
      type II iodothyronine deiodinase (Dio2) and type III iodothyronine deiodinase
      (Dio3) mRNA levels were also measured to assess disruption of TH synthesis.
      Results showed that significant metamorphic delay and mortality increased were
      caused in larvae exposed to 100mg/L NO3-N. The larvae exposed to 100mg/L NO3-N
      clearly exhibited a greater reduction in thyroxine (T4) and 3,5,3'
      triiodothyronine (T3) levels. Moreover, treatment with NO3-N induced down
      regulation of Dio2 mRNA levels and up-regulation of Dio3 mRNA levels, reflecting
      the disruption of thyroid endocrine. It seems that increased mass and body size
      may be correlated with prolonged metamorphosis. Interestingly, we observed an
      exception that exposure to 100mg/L NO3-N did not exhibit remarkable alterations
      of thyroid gland size. Compared with control groups, 100mg/L NO3-N caused partial
      colloid depletion in the thyroid gland follicles. These results suggest that
      nitrate can act as a chemical stressor inducing retardation in development and
      metamorphosis. Therefore, we concluded that the presence of high concentrations
      nitrate can influence the growth, decline the survival, impair TH synthesis and
      induce metamorphosis retardation of B. gargarizans larvae.

PMID- 26210190
TI  - Short- and Long-Term Effects of Abdominal Lipectomy on Weight and Fat Mass in
      Females: a Systematic Review.
AB  - Adipose tissue is considered as an endocrine organ, which is developed in
      specific depots, distinguished either as subcutaneous or visceral. Lipectomy, by
      means of liposuction or abdominoplasty, is a common plastic surgery procedure,
      which can remove substantial amounts of subcutaneous fat. This systematic review
      aims to evaluate the impact of surgical removal of abdominal subcutaneous adipose
      tissue on body weight and fat mass in females in the short- and long-term. A
      systematic review was conducted using a predetermined protocol established
      according to the Cochrane Handbook's recommendations. PubMed, Scopus, CENTRAL,
      and the Cochrane Library were searched from inception to December 2014. Eligible
      studies were prospective studies with >=1 month of follow-up that included female
      only individuals who underwent lipectomy of the abdominal region and reported on
      body weight, body mass index (BMI), or fat mass. Ten studies were included in
      this systematic review with a total of 231 individuals. A significant weight loss
      and BMI improvement were reported in 4 out of 5 studies with a mean follow-up of
      1-2 months, but in none of the 5 studies with a longer follow-up (3-20 months).
      Fat mass showed a similar to weight change. The risk of bias was low for the two
      clinical trials but high for the observational studies included in the review.
      This systematic review revealed only a transient effect of abdominal lipectomy in
      body fat and weight in women, which fades a few months after the operation. These
      results corroborate the evidence from experimental and clinical studies, which
      support fat redistribution and compensatory fat growth, as a result of feedback
      mechanisms, triggered by fat removal. Additional clinical studies, with adequate
      follow-up, may further elucidate the long-term effects of abdominal lipectomy in
      body weight and composition. Systematic review registration PROSPERO
      CRD42015017564 ( www.crd.york.ac.uk/PROSPERO ). 

PMID- 26210191
TI  - Spectrum of Gastric Histopathologies in Severely Obese American Patients
      Undergoing Sleeve Gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a commonly performed weight
      loss procedure, but the pathologic findings in sleeve specimens have not been
      investigated in a US population. METHODS: We performed a retrospective review of
      histopathologic findings in LSG specimens from 310 consecutive bariatric patients
      at the Hershey Medical Center between June 2008 and August 2014. RESULTS:
      Patients were 19 to 75 years old (mean 45 years) with a female-to-male ratio of
      3:1. The histopathologic findings included the following: no pathological
      alteration in 214 patients (69.0 %), chronic inactive gastritis in 41 (13.2 %),
      fundic gland polyp in 17 (5.5 %), proton pump inhibitor therapy effect in 12 (3.9
      %), Helicobacter pylori (H. pylori)-associated chronic active gastritis in 10
      (3.2 %), chronic active gastritis (H. pylori negative) in 5 (1.6 %), chronic
      gastritis with intestinal metaplasia in 4 (1.0 %), gastrointestinal stromal tumor
      (GIST) in 3 (1.0 %), and hyperplastic polyp, granulomatous inflammation,
      xanthogranulomatous inflammation, and mucosal ulceration in 1 patient each (0.3
      %). Prior endoscopy was performed in 8 patients (2.6 %) for unrelated causes, and
      the results did not change the surgical management. Nine patients (2.9 %) had a
      concurrent liver biopsy for visual evidence of significant hepatic fibrosis.
      CONCLUSION: Although most cases showed no pathologic alteration, a minority had
      significant findings, with the incidence of GISTs higher than that reported in
      other series. Despite negative preoperative H. pylori testing, 3.2 % were still
      histologically positive, raising questions about the accuracy of preoperative
      methods used for H. pylori testing and treatment. Preoperative endoscopy may not
      be needed in sleeve patients.

PMID- 26210192
TI  - Laparoscopic Revision of an Omega Loop Gastric Bypass to Treat Afferent Loop
      Syndrome.
AB  - The omega loop gastric bypass (OLGB) has become a very commonly performed
      bariatric procedure because of the advantages it carries over the Roux en Y
      gastric bypass (RYGBP). However, mini gastric bypass is a misnomer, as this
      procedure is more malabsorptive than the RYGBP. Recently, it is called single or
      one anastomosis gastric bypass. The omega loop procedure is associated with a
      risk of afferent loop syndrome, a known complication of the Billroth II
      (Finsterer) operation. This rare complication of the OLGB can be debilitating,
      serious, and deadly. Afferent loop syndrome should be suspected in case of
      malabsorption syndrome with chronic diarrhea, steatorrhea, iron-deficiency
      anemia, edema, emaciation, and osteomalacia and also in case of simple biological
      anomalies such as macrocytosis or megaloblastic anemia. The diagnosis can be
      confirmed by measuring bacterial overgrowth, although this requires a jejunal
      aspirate performed during endoscopy with jejunal intubation. A microbial
      population of more than 106 organisms per milliliter of aspirate is pathological.
      Afferent loop syndrome is encountered less frequently now that the number of
      gastrectomies has dropped. Yet, with the omega loop bypass procedure becoming
      more common, surgeons must again be made aware of this potential complication. 

PMID- 26210193
TI  - Routine Postoperative Monitoring after Bariatric Surgery in Morbidly Obese
      Patients with Severe Obstructive Sleep Apnea: ICU Admission is not Necessary.
AB  - BACKGROUND AND STUDY AIM: Obstructive sleep apnea (OSA) occurs in 70-80% of
      bariatric surgery patients. Patients with severe OSA (apnea/hypopnea index (AHI)
      >30/h) are postoperatively admitted to an intensive care unit (ICU) for
      continuous monitoring, to prevent complications. The aim of this study was to
      assess the necessity of routine postoperative monitoring at an ICU of severe OSA
      patients after bariatric surgery, attempting to prevent and detect
      cardiorespiratory complications. METHODS: Patients undergoing bariatric surgery
      from November 2010 to July 2013 were entered into a database. Minimal follow-up
      was 1 month. Poly(somno)graphy (P(S)G) was routinely performed. Patients with
      severe OSA were admitted to the ICU for the first postoperative night. Oxygen
      saturation was continuously measured. The database was reviewed regarding patient
      characteristics, CPAP use, re-intubations, desaturations (saturation <90% and
      severe <85%), and complications. RESULTS: Severe OSA was present in 151 of the
      794 patients, and all 151 were admitted to the ICU. Thirty who underwent
      revisional surgery were excluded. Forty-seven percent was male, median age was 51
      years (27.0-68.0), and median body mass index (BMI) was 46.6 (kg/m(2)) (34.0
      77.6). No deaths, re-intubations, or cardiopulmonary complications occurred.
      Eighty-two (67.8%) patients used continuous positive airway pressure (CPAP).
      Twenty-one (17.4%) patients experienced desaturations with a median of 2.0 (1-8).
      Six patients (5.0%) had one episode of severe desaturation. CONCLUSION: Patients
      with severe OSA and adequate CPAP use are at low risk of cardiopulmonary
      complications after (laparoscopic) bariatric surgery. Routine admission to an ICU
      might be superfluous. However, continuous digital oximetry remains essential.

PMID- 26210194
TI  - Influence of Insulin Resistance Status on the Development of Gallstones Following
      Roux-En-Y Gastric Bypass: a Prospective Cohort Study.
AB  - BACKGROUND: The occurrence of gallstones following Roux-en-Y gastric bypass
      (RYGB) has been extensively reported. As RYGB promotes improvement in insulin
      resistance (IR), which is one of the factors enrolled in the pathophysiology of
      gallstones, this study aims to determine the influence of IR and its post-RYGB
      course on the development of gallstones. METHODS: This is a prospective cohort
      study that enrolled 108 morbidly obese subjects free of gallstones which
      underwent RYGB and were followed up for 24 months, through clinical, laboratory,
      and ultrasound examinations. IR was assessed through the surrogate marker
      homeostasis model assessment (HOMA). RESULTS: Of the individuals evaluated, 29
      (26.8%) developed gallstones following RYGB. In the univariate analysis,
      postsurgical gallstones were associated with preoperative HOMA (p < 0.0001),
      preoperative fasting glucose (p = 0.0019), preoperative fasting insulin (p =
      0.0001), and preoperative triglycerides (p = 0.0001). Multivariate analysis
      revealed that preoperative HOMA was the only factor independently associated with
      gallstones (p < 0.0001). The incidence of gallstones among individuals with IR
      was 46.8%; in the non-IR subjects, the incidence was 7.4% (p < 0.0001).
      Preoperative IR led to a relative risk of 6.02 (95% CI = 2.1-17.3; p = 0.0009) of
      gallstones. CONCLUSIONS: As gallstones often occur following RYGB, there is
      controversy regarding their management. Some authors propose systematic
      cholecystectomy along with RYGB, while others suggest that the aggregate risk of
      the concomitant approach is significantly higher. As IR was a significant risk
      factor in this study, an individualized approach for this population may be
      proposed. Further research is needed to confirm these findings.

PMID- 26210196
TI  - In developmental science, there is an essential recognition of the complexity of
      human development. Introduction.

PMID- 26210195
TI  - A Systematic Review and Meta-analysis of the Effect of Gastric Bypass Surgery on
      Plasma Lipid Levels.
AB  - BACKGROUND: Obesity-related dyslipidaemia comprises hypercholesterolaemia,
      hypertriglyceridaemia, low HDL-cholesterol and normal to raised LDL-cholesterol
      levels. 40% of morbidly obese surgical patients have dyslipidaemia. Roux-en-Y
      gastric bypass (RYGB) surgery has many beneficial metabolic effects, but the full
      impact on plasma lipids has not been clearly defined. METHODS: A systematic
      review of electronic databases (Ovid; Medline; PubMed; Embase) between 1960 and
      March 2012 was performed using search terms including the following: obesity
      surgery, bariatric surgery, gastric bypass, cholesterol, lipids, triglycerides
      and non-esterified fatty acids. A total of 2442 manuscripts were screened. Papers
      with paired plasma lipid levels around RYGB surgery were included. Exclusions
      included the following: editorials, dual publications, n < 10, resulting in 75
      papers of relevance. A meta-analysis was performed of the effect of RYGB surgery
      upon plasma lipids at different time points up to 4 years following surgery,
      using a random effects model. RESULTS: Paired data were available for 7815
      subjects around RYGB surgery for morbid obesity with a baseline BMI 48 kg/m(2) (n
      = 2331). There was a reduction in plasma total cholesterol and LDL-C from 1 month
      up to 4 years post-RYGB (p < 0.00001, p < 0.00001). Following RYGB, HDL-C
      increased from 1 year onwards (p < 0.00001), and triglyceride levels were reduced
      postoperatively from 3 months up to 4 years (p < 0.00001). NEFA levels were
      increased at 1 month postoperatively (p = 0.003), but from 3 months onwards did
      not differ from preoperative levels (p = 0.07). CONCLUSIONS: RYGB surgery
      reverses the dyslipidaemia of obesity. These findings support the use of RYGB in
      the management of high cardiovascular risk lipid profiles in morbid obesity.

PMID- 26210197
TI  - The Adolescent and Young Adult with Cancer: A Developmental Life Course
      Perspective.
AB  - OBJECTIVES: Using a Life Course Health Development framework, this article
      summarizes what is known about the impact of cancer and its treatment on the
      biopsychosocial world of the adolescent and young adult. DATA SOURCES: Published
      peer reviewed literature, web-based resources, and cancer-related professional
      organizations' resources. CONCLUSION: Adolescents and young adults with cancer,
      between 15 and 29 years of age, have emerged as a distinct group requiring
      specialized care. The demands of cancer and its treatment are often directly
      counter to the developmental needs of this age group and often alter those life
      course experiences that contribute to resilience, thriving, and flourishing.
      IMPLICATIONS FOR NURSING PRACTICE: Providing high-quality care to this age group
      requires a depth of understanding of the complexity of factors that merge to
      influence the developmental life course.

PMID- 26210198
TI  - Inclusion of Adolescents and Young Adults in Cancer Clinical Trials.
AB  - OBJECTIVES: To discuss recent and current initiatives to increase enrollment of
      adolescents and young adult (AYA) cancer patients onto National Cancer Institute
      funded clinical trials to improve outcomes. DATA SOURCES: Peer-reviewed
      publications, websites of professional organizations. CONCLUSION: Despite many
      challenges facing AYAs, recent studies illustrate that AYA-focused cancer
      clinical trials can be successfully developed and conducted. Development of the
      National Cancer Institute National Clinical Trials Network and related AYA
      focused initiatives create new opportunities to expand clinical trials that serve
      AYAs. IMPLICATIONS FOR NURSING PRACTICE: Nurses can influence AYA outcomes by
      leveraging their roles as educators and collaborators to increase participation
      in cancer clinical trials.

PMID- 26210199
TI  - Measures and Methods for Symptom and Symptom Cluster Assessment in Adolescents
      and Young Adults with Cancer.
AB  - OBJECTIVES: To provide an overview of resources for measuring symptoms and
      symptom clusters in adolescents and young adults (AYAs) with cancer and to
      examine methodological strategies for evaluating symptom clusters. DATA SOURCES:
      Published research articles and clinical experience. CONCLUSION: Limited research
      has addressed symptoms and symptom clusters in AYAs with cancer. Reliable, valid,
      and developmentally appropriate measures are needed to advance this area of
      research. IMPLICATIONS FOR NURSING PRACTICE: Use of mobile technology and mixed
      qualitative and quantitative methods to understand AYAs' experience of symptoms
      and symptom clusters could enhance symptom awareness and the evidence base for
      practice.

PMID- 26210200
TI  - Toxicity of Cancer Therapy in Adolescents and Young Adults (AYAs).
AB  - OBJECTIVES: To identify treatment-related toxicities that are either more
      frequent or more severe in the adolescent and young adult (AYA) oncology
      population. To explore differences in drug pharmacology and patient physiology
      that contribute to toxicities in the AYA population and to describe the impact of
      treatment-related toxicities on outcomes for AYA patients. DATA SOURCES: A PubMed
      search was undertaken using the key words Adolescent Young Adult Oncology, AYA,
      toxicity, bone marrow transplant, late effects, and chemotherapy. Additional
      toxicity information was also obtained from recent publications from cancer
      cooperative groups treating AYA patients. CONCLUSION: AYA patients often
      experience more severe toxicities than children when treated with identical
      chemotherapy regimens, which can interfere with successful administration of
      planned treatment, as well as have profound effects on quality of life. AYA
      patients with cancer face the dual challenge of disease biology associated with
      inferior response to treatment, thus necessitating treatment intensification,
      while at the same time suffering higher rates of specific toxicities such as
      vincristine-induced neuropathy, osteonecrosis, and treatment-related mortality
      caused by infection. IMPLICATIONS FOR NURSING PRACTICE: AYA patients are at a
      higher risk for toxicities from regimens that may be tolerated by younger
      patients. Staff should be aware of toxicities facing this population so that
      appropriate supportive care measures can be utilized. Future research on the
      pharmacology of drugs in adolescence, hormonal effects on drug-metabolizing
      enzymes, cumulative exposure to different drugs in combination, and risk and
      severity of specific toxicities will be critical to improving the treatment of
      AYA patients.

PMID- 26210201
TI  - Spirituality and Spiritual Care of Adolescents and Young Adults with Cancer.
AB  - OBJECTIVES: To review research on spiritual perspectives and spiritual care of
      adolescents and young adults (AYA) living with cancer. DATA SOURCES: Peer
      reviewed publications, book chapters, and websites of professional organizations.
      CONCLUSION: There is a paucity of research specifically investigating AYA
      spirituality and lack of AYA-sensitive instruments to measure spirituality.
      Research that applies robust scientific methods to the study of AYA spirituality
      is needed. Research that provides evidence on which to base best practices for
      spiritual care that supports AYA spiritual well-being is likewise necessary.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses can influence AYA health-related
      outcomes and experiences by providing ethical and evidence-based spiritual
      nurture.

PMID- 26210202
TI  - Psychosocial Interventions for Adolescents and Young Adults with Cancer.
AB  - OBJECTIVES: To summarize and evaluate the studies published since 2007 on
      psychosocial interventions designed for adolescents and young adults (AYA) with
      cancer. DATA SOURCES: PubMed, Ovid, and PsycINFO. CONCLUSION: Our review confirms
      that the development and evaluation of psychosocial interventions for AYA is
      still in its infancy. Only five studies were identified and these generally had
      small samples and limited results. IMPLICATIONS FOR NURSING PRACTICE: It is
      important for nurses to assess the needs of AYA. Incorporating creative ways for
      AYA to express their needs and self-reflect seems to be critically important and
      may help AYA cope positively with the cancer experience.

PMID- 26210204
TI  - Susceptibility testing of Mycobacterium abscessus by isothermal microcalorimetry.
AB  - We evaluated a new method for susceptibility testing of a rapidly growing
      mycobacterium using real-time measurement of heat (microcalorimetry). MICs of 2
      clinical Mycobacterium abscessus isolates were determined by microbroth dilution
      and E-test. For microcalorimetry, Middlebrook-7H10 agar+10% oleic acid-albumin
      dextrose-catalase, containing amikacin, clarithromycin, linezolid, and
      ciprofloxacin was inoculated with ~10(5)CFU/mL. Heat production was measured at
      37 degrees C for 72h. Minimal heat inhibition concentration (MHIC) was defined as
      the lowest antibiotic concentration inhibiting growth-related heat production.
      Growth of M. abscessus was detected after a median of 16.5h (range, 8.5-26.9h).
      Heat detection was proportionally delayed with increasing concentration of
      antibiotics. MHICs for the tested strains were 16 to >16mg/L for amikacin, >8mg/L
      for clarithromycin, 4 to >16mg/L for ciprofloxacin, 24 to >32mg/L for linezolid.
      MHICs were in agreement within two 2-fold dilutions with conventional MICs.
      Microcalorimetry may accelerate antimicrobial susceptibility testing in
      mycobacteria and provide additional real-time information on the drug effect. 

PMID- 26210203
TI  - Models of Cancer Survivorship Care for Adolescents and Young Adults.
AB  - OBJECTIVES: To review the literature on adolescent and young adult (AYA)
      oncology, discuss survivorship models of care, and focus on the unique needs of
      AYA patients with transition of care from treatment to survivorship. DATA
      SOURCES: Peer-reviewed literature, workshop summaries, clinical practice
      guidelines. CONCLUSION: Advancements have been made for AYAs with regard to
      identifying risk factors from cancer treatment and the need for ongoing follow-up
      care. Survivors face several unique care transitions. Several models of
      survivorship care are available for AYAs. IMPLICATIONS FOR NURSING PRACTICE: The
      responsibilities of survivorship care for AYA patients fall on clinical
      providers, researchers, the government, advocacy groups as well as the survivors
      and families themselves. Nurses must remain cognizant and educated on AYA
      survivorship issues.

PMID- 26210205
TI  - Autologous antibodies that bind neuroblastoma cells.
AB  - Antibody therapy of neuroblastoma is promising and our goal is to derive
      antibodies from patients with neuroblastoma for developing new therapeutic
      antibodies. The feasibility of using residual bone marrow obtained for clinical
      indications as a source of tumor cells and a source of antibodies was assessed.
      From marrow samples, neuroblastoma cells were recovered, grown in cell culture
      and also implanted into mice to create xenografts. Mononuclear cells from the
      marrow were used as a source to generate phage display antibody libraries and
      also hybridomas. Growth of neuroblastoma patient cells was possible both in vitro
      and as xenografts. Antibodies from the phage libraries and from the monoclonal
      hybridomas bound autologous neuroblastoma cells with some selectivity. It appears
      feasible to recover neuroblastoma cells from residual marrow specimens and to
      generate human antibodies that bind autologous neuroblastoma cells. Expansion of
      this approach is underway to collect more specimens, optimize methods to generate
      antibodies, and to evaluate the bioactivity of neuroblastoma-binding antibodies. 

PMID- 26210206
TI  - Non-invasive or minimally invasive autopsy compared to conventional autopsy of
      suspected natural deaths in adults: a systematic review.
AB  - OBJECTIVES: Autopsies are used for healthcare quality control and improving
      medical knowledge. Because autopsy rates are declining worldwide, various non
      invasive or minimally invasive autopsy methods are now being developed. To
      investigate whether these might replace the invasive autopsies conventionally
      performed in naturally deceased adults, we systematically reviewed original
      prospective validation studies. MATERIALS AND METHODS: We searched six databases.
      Two reviewers independently selected articles and extracted data. Methods and
      patient groups were too heterogeneous for meaningful meta-analysis of outcomes.
      RESULTS: Sixteen of 1538 articles met our inclusion criteria. Eight studies used
      a blinded comparison; ten included less than 30 appropriate cases. Thirteen
      studies used radiological imaging (seven dealt solely with non-invasive
      procedures), two thoracoscopy and laparoscopy, and one sampling without imaging.
      Combining CT and MR was the best non-invasive method (agreement for cause of
      death: 70 %, 95%CI: 62.6; 76.4), but minimally invasive methods surpassed non
      invasive methods. The highest sensitivity for cause of death (90.9 %, 95%CI:
      74.5; 97.6, suspected duplicates excluded) was achieved in recent studies
      combining CT, CT-angiography and biopsies. CONCLUSION: Minimally invasive
      autopsies including biopsies performed best. To establish a feasible alternative
      to conventional autopsy and to increase consent to post-mortem investigations,
      further research in larger study groups is needed. KEY POINTS: * Health care
      quality control benefits from clinical feedback provided by (alternative)
      autopsies. * So far, sixteen studies investigated alternative autopsy methods for
      naturally deceased adults. * Thirteen studies used radiological imaging
      modalities, eight tissue biopsies, and three CT-angiography. * Combined CT, CT
      angiography and biopsies were most sensitive diagnosing cause of death.

PMID- 26210207
TI  - Subtracted Dynamic MR Perfusion Source Images (sMRP-SI) provide Collateral Blood
      Flow Assessment in MCA Occlusions and Predict Tissue Fate.
AB  - OBJECTIVES: Collateral blood flow is accepted as a predictive factor of tissue
      fate in ischemic stroke. Thus, we aimed to evaluate a new method derived from MR
      perfusion source images to assess collateral flow in patients with ICA/MCA
      occlusions. METHODS: A total of 132 patients of the prospective 1000+ study were
      examined. MR perfusion source images were assessed according to Deltaimg_n =
      img_n + 1 - img_n - 1 using the five-grade Higashida collateral flow rating
      system. Higashida scores were correlated to mismatch (MM) volume, mismatch ratio,
      day 6 FLAIR lesion volumes and day 90 mRS. RESULTS: Patients with Higashida
      scores 3 and 4 had significantly lower admission NIHSS, smaller FLAIR day 6
      lesion volumes (p < 0.001) and higher rates of better long-term outcome (mRS 0-2,
      p = 0.002). There was a linear trend for the association of Higashida grade 1 (p
      = 0.002) and 2 (p = 0.001) with unfavourable outcome (day 90 mRS 3-6), but no
      significant association was found for MM volume, MM ratio and day 90 mRS. Inter
      rater agreement was 0.58 (95% CI 0.43-0.73) on day 1, 0.70 (95% CI 0.58-0.81) on
      day 2. CONCLUSION: sMRP-SI Higashida score offers a non-invasive collateral
      vessel and tissue perfusion assessment of ischemic tissue. The predictive value
      of Higashida rating proved superior to MM with regard to day 90 mRS. KEY POINTS:
      * Assessment of collateral flow using subtracted dynamic MR perfusion source
      imaging (sMRP-SI). * sMRP-SI offers additional information about morphological
      characteristics of ischemic brain tissue. * sMRP-SI collateral flow assessment
      proves superior to mismatch volume. * Better collateral flow was significantly
      associated with better outcome (day 90 mRS).

PMID- 26210208
TI  - A Molecular Dynamics Study of Allosteric Transitions in Leishmania mexicana
      Pyruvate Kinase.
AB  - A comparative molecular dynamics analysis of the pyruvate kinase from Leishmania
      mexicana is presented in the absence and presence of the allosteric effector
      fructose 2,6-bisphosphate. Comparisons of the simulations of the large 240 kDa
      apo and holo tetramers show that binding of fructose 2,6-bisphosphate cools the
      enzyme and reduces dynamic movement, particularly of the B-domain. The reduced
      dynamic movement of the holo form traps the pyruvate kinase tetramer in its
      enzymatically active state with the B-domain acting as a lid to cover the active
      site. The simulations are also consistent with a transition of the mobile active
      site alpha6' helix, which would adopt a helical conformation in the active R
      state and a less structured coil conformation in the inactive T-state. Analysis
      of the rigid body motions over the trajectory highlights the concerted
      anticorrelated rigid body rocking motion of the four protomers, which drives the
      T to R transition. The transitions predicted by these simulations are largely
      consistent with the Monod-Wyman-Changeux model for allosteric activation but also
      suggest that rigidification or cooling of the overall structure upon effector
      binding plays an additional role in enzyme activation. 

PMID- 26210209
TI  - Nootropic Effects of Filipendula Vulgaris Moench Water Extract Fractions.
AB  - Nootropic activity of water extract fractions from aerial parts of Filipendula
      vulgaris Moench was demonstrated on the models of hermetic volume hypoxia,
      conditioned passive avoidance response, open field test, and forced swimming with
      a load. The fractions stimulated hypoxic resistance, normalized orientation and
      exploratory behavior, improved conditioned response reproduction during testing
      after hypoxic injury, and increased exercise tolerance. Fractionation of the
      extract led to dissociation of the effect components, which suggests that
      individual constituents have specific characteristics. Ethylacetate fraction
      exhibited most pronounced nootropic activity and was superior to plant extract by
      some characteristics. The detected effects seemed to be caused by modulation of
      the hippocampus activity the under the effects of phenol and triterpene
      compounds.

PMID- 26210210
TI  - Brassinosteroid-BODIPY conjugates: Design, synthesis, and properties.
AB  - Three BS-BODIPY (brassinosteroids-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)
      conjugates were synthesized and their fluorescent and immunological properties
      were investigated. Two of the conjugates, having present all the functional
      groups characteristic of BS, were shown to be potentially useful as biological
      probes to study involvement of BS into physiological processes in living cells. 

PMID- 26210212
TI  - ISCD in 2015: State of the Society.
AB  - This piece offers an opportunity for the International Society for Clinical
      Densitometry's immediate past president to reflect on the past year and provide
      an update on the state of our society as we continue to move forward. 

PMID- 26210211
TI  - Synthesis of antiproliferative 13alpha-d-homoestrones via Lewis acid-promoted one
      pot Prins-Ritter reactions of d-secosteroidal delta-alkenyl-aldehydes.
AB  - A simple one-pot Prins-Ritter route was developed for the synthesis of 16
      acylamino-17a-hydroxy-d-homoestrone 3-benzyl and 3-methyl ethers in the 13alpha
      estrone series. The d-secosteroidal delta-alkenyl-aldehydes were allowed to react
      with different nitriles in the presence of BF3.OEt2 as a Lewis acid catalyst.
      Prins cyclizations afforded 17a-hydroxy-16-carbenium ions, which underwent Ritter
      reactions with nitriles, leading to 16alpha- or 16beta-acylamino derivatives. A
      side-product in which a dihydro-1,3-oxazine was bridged to six-membered ring D at
      positions 16alpha,17aalpha was formed in each reaction. The antiproliferative
      properties of the novel 13alpha-d-homosteroids were determined on a panel of
      human adherent cancer cell lines (HeLa, MCF-7, T47D, MDA-MB-231, MDA-MB-361,
      A2780 and A431) by means of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) assays. Some compounds proved to be more effective
      (with submicromolar IC50 values) than the reference agent cisplatin. One of the
      most potent compounds substantially increased the rate of tubulin polymerization.
      Cell cycle analyses by flow cytometry indicated a concentration-dependent
      accumulation of the G2/M cell population. 

PMID- 26210214
TI  - [X-ray diagnostics in dentistry].

PMID- 26210213
TI  - Sarcopenia, the Next Frontier in Fracture Prevention: Introduction From the Guest
      Editors.
AB  - In this issue of the Journal of Clinical Densitometry, articles consider
      sarcopenia epidemiology, current and future approaches to diagnosis, tools to
      assess muscle mass and/or function, the roles of vitamin D and nutrition in
      general in sarcopenia, and finally the care of patients with this condition. All
      authors have taken a clinical approach to their topic area and provide bulleted
      key messages as the most salient points. 

PMID- 26210216
TI  - [Dentistry in the Middle Ages in the low lands 5. "Van tanden uut te doene metter
      wortele"].

PMID- 26210215
TI  - [Safety of intravenous sedation with midazolam for dental treatment].
AB  - In the December 2014 issue of the Nederlands Tijdschrift voor Tandheelkunde, T.H.
      van den Berg and B. Preckel published an article entitled 'Mild intravenous
      sedation with midazolam by dentists'. Broers et al responded to this article
      arguing that the administration of intravenous sedation with midazolam by
      dentists is unsafe for patients. In the current article the authors, Van den Berg
      and Preckel, address the points of criticism. 

PMID- 26210217
TI  - [Oral and maxillofacial radiology: laws and regulations].
AB  - Since the discovery of X-rays, medical imaging has been one of its most important
      applications. In the course of years, understanding of the potentially harmful
      effects of radiation on tissue has substantially increased as a result of
      experience and scientific studies. This has led to the International Commission
      on Radiological Protection (ICRP), the organisation that is now regarded as the
      most authoritative in the field of information on radiation and radiation
      protection. In most countries the law governing radiation is based on the 3
      principles of the ICRP: justification, ALARA and dosage limits. For the Dutch
      situation, these are the Nuclear Energy Act (Kernenergiewet) and the Radiation
      Protection Decree (Besluit stralingsbescherming). The Practice Guidelines on
      Radiology are available for the practical implementation of the regulations. By
      working according to the Practice Guidelines, the dentist satisfies the legal
      regulations, but, more importantly, he can apply X-ray diagnostics in a manner
      that is safe for him, the dental team, the patients and all other visitors of the
      practice. 

PMID- 26210218
TI  - [The ALARA-principle. Backgrounds and enforcement in dental practices].
AB  - Optimization of radiation protection began soon after the discovery of X-rays.
      The optimization-concept has been refined more and more as a result of increa
      sing knowledge of radiation and its effect on people. Since 1973 the acronym
      ALARA (As Low As Reasonably Achievable) has been used to designate the
      optimization of X-ray doses. For the dentist the ALARA-principle entails the
      obligation to minimize the radiation dose to patient and surroundings to a level
      as low as reasonably achievable. Currently in radiology the acronym ALADA is also
      used: As Low As Diagnostically Acceptable. To establish ALARA goals Diagnostic
      Reference Levels are employed in medical radiology. These Diagnostic Reference
      Levels are also being introduced in dental radiology. Practical measures for
      ALARA/ALADA in dental practice comprise an awareness of the field of view (for
      all types of imaging, including cone beam computed tomography) exposure time, and
      relation to anatomy and diagnostic justification, and shielding. 

PMID- 26210219
TI  - [Indications for and frequency of intraoral radiographs].
AB  - Radiographs are essential in dental practice today. Due to the exposure of
      patients to X-rays every radiograph has to be justified. The advantages and
      disadvantages of risks and diagnostic rewards have to be weighed against one
      another whenever X-ray imaging is considered. An important factor in this respect
      is the usefulness (in terms of sensitivity and specificity) of a radiograph and
      along with that, the monitoring of the quality of the entire process, from
      positioning the photo up to and including the development or scanning of it. Both
      for children and adults the indication for taking radiographs must be made on an
      individual basis. The most important considerations are: caries experience, oral
      hygiene and nutritional habits and exposure to fluorides. Based on these factors
      an individual risk assessment can be made and the possible benefit of bitewing
      radiographs for the dental treatment can be determined. European guidelines give
      advice on the indications and frequency of radiographs in, among other fields,
      periodontology, endodontology and implantology. 

PMID- 26210220
TI  - [The dental radiograph: pitfalls and surprises].
AB  - Guidelines allow retakes of dental radiographs of up to 10%. In the general
      practice the percentage of retakes is considerably higher. In intraoral
      radiography film positioning and faults in directing the collimator are the most
      common reasons for retakes. The use of film holders and correctly aiming the
      collimator decrease the risk of failure. In panoramic radiography the positioning
      of the patient in the x-ray machine and the palatoglossal air space are the main
      causes of failure of radiographs. A systematic approach, a thorough check of the
      radiation area for artefacts and the use of the available laser lines decrease
      the risk of a diagnostically unacceptable radiograph. 

PMID- 26210221
TI  - [Radiobiological aspects of diagnostic X-ray use in dentistry].
AB  - Soon after the discovery of X-rays, it became clear that their use can cause
      detrimental effects. The field of radiobiology deals with these detrimental
      effects. In this article, the theoretical concepts of radiobiology relevant to
      diagnostic X-ray use are presented. The effects of radiation on living tissues,
      the relationship between dose and effect, and a translation of these effects into
      the dental application are discussed. X-rays cannot be considered to be harmless
      even when used at the relatively low doses as in dentistry. If applied with
      justification and optimization, the risk to the patient will, however, be small. 

PMID- 26210222
TI  - Is There a Role for Homeopathy in Cancer Care? Questions and Challenges.
AB  - Patients with cancer commonly use complementary and integrative medicine,
      including homeopathy. Homeopathy has grown in popularity with the public but is
      viewed with skepticism by medical academia and is still excluded from
      conventionally prescribed treatments. In recent years, homeopathy has been used
      in cancer care in Europe and other countries worldwide. This use raised the
      question if there is any benefit in utilizing this type of care with cancer
      patients. The purpose of this manuscript is to explore the evidence related to
      the benefit of homeopathy in cancer care. Limited research has suggested that
      homeopathic remedies appear to cause cellular changes in some cancer cells. In
      animal models, several homeopathic remedies have had an inhibitory effect on
      certain tumor development. Some clinical studies of homeopathic remedies combined
      with conventional care have shown that homeopathic remedies improve quality of
      life, reduce symptom burden, and possibly improve survival in patients with
      cancer. The findings from several lab and clinical studies suggest that
      homeopathy might have some beneficial effect in cancer care; however, further
      large, comprehensive clinical studies are needed to determine these beneficial
      effects. Although additional studies are needed to confirm these findings, given
      the low cost, minimal risks, and the potential magnitude of homeopathy's effects,
      this use might be considered in certain situations as an additional tool to
      integrate into cancer care. 

PMID- 26210223
TI  - The clinical importance of parathyroid atypia: is long-term surveillance
      necessary?
AB  - BACKGROUND: The uncommon diagnosis of atypical parathyroid adenoma (APA) creates
      a clinical conundrum for surveillance. We evaluated a large series of APA to
      determine long-term outcomes. METHODS: Prospectively collected data were
      retrieved for patients with a diagnosis of histologic APA defined by presence of
      >=2 criteria: clinical/intraoperative adherence, fibrotic bands, trabecular
      growth, or mitotic rate of >1/10 per high-power field without indisputable signs
      of malignancy. Follow-up was at 2 weeks, 6 months, and yearly thereafter.
      RESULTS: From 1970 to 2014, 51 patients (1.2%) with primary hyperparathyroidism
      had a diagnosed APA. Mean age was 56 years (range, 19-83), and 61% were women.
      Intraoperatively, 11 of 51 glands (22%) were adherent, requiring concurrent
      thyroid lobectomy. Common microscopic findings were fibrosis (78%), trabecular
      growth (37%), and increased mitotic count (24%); the mean APA weight was 3.14 g
      (range, 167 mg-38 g). Loss of heterozygosity occurred in 25 of 38 tested patients
      (66%) at the p21 locus in 9 cases, at CDC73 and PTEN in 6, and at RB1 in 4 cases,
      with mean fractional allelic loss of 24% (range, 6-79). With mean follow-up of 5
      years (range, 0.5-18), no patient has developed recurrence. CONCLUSION: Over a
      mean follow-up of 5 years, we observed no recurrences after APA resection.
      Molecular features had no discernable impact, indicating that long-term follow-up
      may be unnecessary.

PMID- 26210224
TI  - Military-to-civilian translation of battlefield innovations in operative trauma
      care.
AB  - BACKGROUND: Historic improvements in operative trauma care have been driven by
      war. It is unknown whether recent battlefield innovations stemming from conflicts
      in Iraq/Afghanistan will follow a similar trend. The objective of this study was
      to survey trauma medical directors (TMDs) at level 1-3 trauma centers across the
      United States and gauge the extent to which battlefield innovations have shaped
      civilian practice in 4 key domains of trauma care. METHODS: Domains were
      determined by the use of a modified Delphi method based on multiple consultations
      with an expert physician/surgeon panel: (1) damage control resuscitation (DCR),
      (2) tourniquet use, (3) use of hemostatic agents, and (4) prehospital
      interventions, including intraosseous catheter access and needle thoracostomy. A
      corresponding 47-item electronic anonymous survey was developed/pilot tested
      before dissemination to all identifiable TMD at level 1-3 trauma centers across
      the US. RESULTS: A total of 245 TMDs, representing nearly 40% of trauma centers
      in the United States, completed and returned the survey. More than half (n = 127;
      51.8%) were verified by the American College of Surgeons. TMDs reported high
      civilian use of DCR: 95.1% of trauma centers had implemented massive transfusion
      protocols and the majority (67.7%) tended toward 1:1:1 packed red blood
      cell/fresh-frozen plasma/platelets ratios. For the other 3, mixed adoption
      corresponded to expressed concerns regarding the extent of concomitant civilian
      research to support military research and experience. In centers in which
      policies reflecting battlefield innovations were in use, previous military
      experience frequently was acknowledged. CONCLUSION: This national survey of TMDs
      suggests that military data supporting DCR has altered civilian practice.
      Perceived relevance in other domains was less clear. Civilian academic efforts
      are needed to further research and enhance understandings that foster improved
      trauma surgeon awareness of military-to-civilian translation.

PMID- 26210227
TI  - Investigation of meningomyovertebral structures within the upper cervical
      epidural space: a sheet plastination study with clinical implications.
AB  - BACKGROUND CONTEXT: Over the past two decades, soft-tissue structures
      communicating with the dura mater within the epidural space have become the focus
      of many anatomical and histopathologic studies. The relationship between these
      bridging structures has yet to be evaluated in situ. PURPOSE: This is the first
      study that used E12 sheet plastination to investigate the epidural space of the
      upper cervical spine in situ and its associated bridging structures. Given the
      complexity of this space, this study may prove useful to clinical anatomists and
      surgeons who operate within this region. STUDY DESIGN: Anatomical and microscopic
      analyses of structures that communicate with the dura mater within the upper
      cervical region were carried out. METHODS: Gross dissection in conjunction with
      microscopy was used to evaluate bridging communications of the upper cervical
      spine in 10 cadavers. To evaluate the in situ arrangement of these structures,
      E12 sheet plastination was used on 13 cadavers. RESULTS: In all 23 specimens,
      suboccipital fascia coalesced with the dorsal meningovertebral ligament of the
      atlas, and inserted directly into the posterior surface of the dura as a single
      but separable laminar layer. At the level of the atlantoaxial interspace,
      suboccipital fasciae combined and coalesced with the dorsal meningovertebral
      ligament of the atlas and the axis. These structures inserted into the posterior
      surface of the dura mater as a single but separable layer. Microscopy validated
      these findings and E12 sheet plastination revealed the in situ organization of
      these soft-tissue structures. E12 sheet plastination also provided new
      information on dural arrangement at the craniocervical junction, which was
      observed to be composed of periosteum from the occiput but consisted mainly of
      deep fascia from the rectus capitis posterior minor. CONCLUSIONS: E12 sheet
      plastination has provided in situ visualization of bridging structures within the
      cervical epidural space and offers new insight into these structures, as well as
      the composition and arrangement of the posterior atlantooccipital membrane and
      cerebrospinal dura at the craniocervical junction. This study aims to expand on
      the anatomical understanding of the upper cervical region while defining
      structures that may reduce neurosurgical complications, and aid in the
      understanding of the pathophysiology of certain neurogenic disorders.

PMID- 26210225
TI  - Time trends of clinicopathologic features and surgical treatment for gastric
      cancer: Results from 2 high-volume institutions in southern China.
AB  - BACKGROUND: The objective of this study was to evaluate the time-related trends
      of tumor characteristics and postoperative survival of patients with gastric
      cancer (GC) in 2 high-volume centers in high incidence areas of southern China.
      METHODS: Based on the meticulously collected data from 5,327 patients with GC
      treated with operative intervention at Sun Yat-sen University Cancer Center and
      Fujian Medical University Union Hospital, we analyzed the differences in
      clinicopathologic features and postoperative survival over the following 4
      consecutive periods: 1991-1995 (period 1), 1996-2000 (period 2), 2001-2005
      (period 3), and 2006-2010 (period 4). RESULTS: Tumor size decreased (P = .001),
      but the proportion of poorly differentiated tumors increased (P < .001) over the
      study periods. Early GC was diagnosed more often in later periods, gradually
      increasing from 7 to 15% (P < .001). A surprising improvement was observed in the
      mean number of retrieved lymph nodes, ranging from 10.36 to 26.22 (P < .001). The
      radical resection rate increased from 88 to 93%. The overall 5-year survival rate
      improved steadily over the 4 periods, from 39 to 53% (P < .001). Multivariate
      analysis revealed that age, tumor location, histologic type, tumor size, depth of
      invasion, lymphatic invasion, number of retrieved lymph nodes, radical resection,
      and time periods were independent prognostic factors. CONCLUSION: The
      clinicopathologic features of tumors changed during the observation period in our
      region. The increasingly early detection of patients with GC and more
      standardized regimens for operative management, including routinely performed D2
      lymphadenectomy, most likely resulted in the increase in overall survival.

PMID- 26210228
TI  - Do diethyl phthalate (DEP) and di-2-ethylhexyl phthalate (DEHP) influence the
      metabolic syndrome parameters? Pilot study.
AB  - The study objective was to determine if the healthy participants were exposed to
      diethyl phthalate (DEP) and di (2-ethylhexyl) phthalate (DEHP) and if this
      exposure could be linked to the development of metabolic syndrome. The study
      included 103 healthy volunteers of similar age with normal BMI values, waist
      circumference, total cholesterol, HDL, LDL, and triglycerides. DEP and DEHP were
      measured in the morning urine samples to detect monoethyl phthalate (MEP) and
      mono-2-ethylhexyl phthalate (MEHP). Two phthalate groups and a control group were
      formed. Both MEP group and control group had similar results. The correlations
      between MEP and the measured parameters were insignificant. The correlation
      between the MEHP group and the age was significantly negative, but between the
      MHEP group and the waist circumference the correlation was significantly
      positive. Lipids and lipoproteins were within the reference values and equal in
      both groups. The significant negative correlation was observed only between MEHP
      and HDL. Our population is exposed to DEP and DEHP. There was only a significant
      correlation between DEHP and the observed metabolic syndrome components. Its
      negative impact was higher as the participants were younger. 

PMID- 26210229
TI  - Is Recreational Soccer Effective for Improving VO2max A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: Soccer is the most popular sport worldwide, with a long history and
      currently more than 500 million active participants, of whom 300 million are
      registered football club members. On the basis of scientific findings showing
      positive fitness and health effects of recreational soccer, FIFA (Federation
      Internationale de Football Association) introduced the slogan "Playing football
      for 45 min twice a week-best prevention of non-communicable diseases" in 2010.
      OBJECTIVE: The objective of this paper was to perform a systematic review and
      meta-analysis of the literature to determine the effects of recreational soccer
      on maximal oxygen uptake (VO2max). METHODS: Six electronic databases (MEDLINE,
      PubMed, SPORTDiscus, Web of Science, CINAHL and Google Scholar) were searched for
      original research articles. A manual search was performed to cover the areas of
      recreational soccer, recreational physical activity, recreational small-sided
      games and VO2max using the following key terms, either singly or in combination:
      recreational small-sided games, recreational football, recreational soccer,
      street football, street soccer, effect, maximal oxygen uptake, peak oxygen
      uptake, cardiorespiratory fitness, VO2max. The inclusion criteria were divided
      into four sections: type of study, type of participants, type of interventions
      and type of outcome measures. Probabilistic magnitude-based inferences for meta
      analysed effects were based on standardised thresholds for small, moderate and
      large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject
      standard deviations for baseline fitness. RESULTS: Seventeen studies met the
      inclusion criteria and were included in the systematic review and meta-analysis.
      Mean differences showed that VO2max increased by 3.51 mL/kg/min (95 % CI 3.07
      4.15) over a recreational soccer training programme in comparison with other
      training models. The meta-analysed effects of recreational soccer on VO2max
      compared with the controls of no exercise, continuous running and strength
      training were most likely largely beneficial [effect size (ES) = 1.46; 95 %
      confidence interval (CI) 0.91, 2.01; I (2) = 88.35 %], most likely moderately
      beneficial (ES = 0.68; 95 % CI 0.06, 1.29; I (2) = 69.13 %) and most likely
      moderately beneficial (ES = 1.08; 95 % CI -0.25, 2.42; I (2) = 71.06 %),
      respectively. In men and women, the meta-analysed effect was most likely largely
      beneficial for men (ES = 1.22) and most likely moderately beneficial for women
      (ES = 0.96) compared with the controls. After 12 weeks of recreational soccer
      with an intensity of 78-84 % maximal heart rate (HRmax), healthy untrained men
      improved their VO2max by 8-13 %, while untrained elderly participants improved
      their VO2max by 15-18 %. Soccer training for 12-70 weeks in healthy women
      resulted in an improvement in VO2max of 5-16 %. Significant improvements in
      VO2max have been observed in patients with diabetes mellitus, hypertension and
      prostate cancer. CONCLUSION: Recreational soccer produces large improvements in
      VO2max compared to strength training and no exercise, regardless of the age, sex
      and health status of the participants. Furthermore, recreational soccer is better
      than continuous endurance running, albeit the additional effect is moderate. This
      kind of physical activity has great potential for enhancing aerobic fitness, and
      for preventing and treating non-communicable diseases, and is ideal for
      addressing lack of motivation, a key component in physical (in)activity.

PMID- 26210230
TI  - MRI appearance of the superior transverse scapular ligament.
AB  - OBJECTIVE: The superior transverse scapular ligament (STSL) forms the roof of the
      suprascapular notch, which is the most common location of entrapment of the
      suprascapular nerve, a cause of shoulder pain and weakness. The purpose of this
      study is to determine the frequency of visualization of the STSL on routine
      shoulder MRIs, to identify the sequences and imaging planes on which it is
      visualized most frequently, and to describe its typical MRI appearance, none of
      which have been previously addressed in the radiologic literature. MATERIALS AND
      METHODS: One hundred twenty-one consecutive shoulder MRIs were reviewed for the
      presence or absence of the STSL, including the imaging plane and sequence that
      best depicted the ligament. Dimensions of the ligament were recorded. RESULTS:
      Fifty four of 121 shoulder MRIs were technically adequate for visualization of
      the STSL, and it was identified on 51 of these studies (94%). There was no
      statistically significant difference between 1.5-T and 3-T systems. The best
      individual sequence for visualizing the STSL was the sagittal T1-weighted
      sequence, in which the STSL was visible on 75/80 technically adequate sequences
      (94%). The sagittal plane was the best plane for visualizing the STSL, in which
      it was visible on 65/69 technically adequate studies (94%). The STSL on average
      measured 12.8 +/- 1.5 mm in transverse dimension. CONCLUSIONS: The STSL can be
      visualized on the majority of shoulder MRIs and is best seen on sagittal T1
      weighted images on our imaging protocol. Evaluation of the STSL can potentially
      help in identifying pathologic conditions affecting the suprascapular nerve.

PMID- 26210231
TI  - Genomic risk prediction of complex human disease and its clinical application.
AB  - Recent advances in genome-wide association studies have stimulated interest in
      the genomic prediction of disease risk, potentially enabling individual-level
      risk estimates for early intervention and improved diagnostic procedures. Here,
      we review recent findings and approaches to genomic prediction model construction
      and performance, then contrast the potential benefits of such models in two
      complex human diseases, aiding diagnosis in celiac disease and prospective risk
      prediction for cardiovascular disease. Early indications are that optimal
      application of genomic risk scores will differ substantially for each disease
      depending on underlying genetic architecture as well as current clinical and
      public health practice. As costs decline, genomic profiles become common, and
      popular understanding of risk and its communication improves, genomic risk will
      become increasingly useful for the individual and the clinician. 

PMID- 26210232
TI  - Plasma gasification of refuse derived fuel in a single-stage system using
      different gasifying agents.
AB  - The renewable evolution in the energy industry and the depletion of natural
      resources are putting pressure on the waste industry to shift towards flexible
      treatment technologies with efficient materials and/or energy recovery. In this
      context, a thermochemical conversion method of recent interest is plasma
      gasification, which is capable of producing syngas from a wide variety of waste
      streams. The produced syngas can be valorized for both energetic (heat and/or
      electricity) and chemical (ammonia, hydrogen or liquid hydrocarbons) end
      purposes. This paper evaluates the performance of experiments on a single-stage
      plasma gasification system for the treatment of refuse-derived fuel (RDF) from
      excavated waste. A comparative analysis of the syngas characteristics and process
      yields was done for seven cases with different types of gasifying agents (CO2+O2,
      H2O, CO2+H2O and O2+H2O). The syngas compositions were compared to the
      thermodynamic equilibrium compositions and the performance of the single-stage
      plasma gasification of RDF was compared to that of similar experiments with
      biomass and to the performance of a two-stage plasma gasification process with
      RDF. The temperature range of the experiment was from 1400 to 1600 K and for all
      cases, a medium calorific value syngas was produced with lower heating values up
      to 10.9 MJ/Nm(3), low levels of tar, high levels of CO and H2 and which
      composition was in good agreement to the equilibrium composition. The carbon
      conversion efficiency ranged from 80% to 100% and maximum cold gas efficiency and
      mechanical gasification efficiency of respectively 56% and 95%, were registered.
      Overall, the treatment of RDF proved to be less performant than that of biomass
      in the same system. Compared to a two-stage plasma gasification system, the
      produced syngas from the single-stage reactor showed more favourable
      characteristics, while the recovery of the solid residue as a vitrified slag is
      an advantage of the two-stage set-up.

PMID- 26210233
TI  - Materials flow analysis of neodymium, status of rare earth metal in the Republic
      of Korea.
AB  - Materials flow analysis of neodymium, status of rare earth elements (REEs) in the
      Republic of Korea has been investigated. Information from various resources like
      the Korean Ministry of Environment, Korea international trade association, United
      Nations Commodity Trade Statistics Database and from individual industry were
      collected and analyzed for materials flow analysis of neodymium. Demand of
      neodymium in the Republic of Korea for the year 2010 was 409.5 tons out of which
      the majority of neodymium, i.e., 68.41% was consumed by domestic electronics
      industry followed by medical appliances manufacturing (13.36%). The Republic
      Korea is one of the biggest consumer and leading exporter of these industrial
      products, absolutely depends on import of neodymium, as the country is lacking
      natural resources. The Republic of Korea has imported 325.9 tons of neodymium
      permanent magnet and 79.5 tons of neodymium containing equipment parts mainly for
      electronics, medical appliances, and heavy/light vehicles manufacturing industry.
      Out of which 95.4 tons of neodymium permanent magnet get exported as an
      intermediate product and 140.6 tons of neodymium in the form of consumable
      products get exported. Worldwide the neodymium is at the high end of supply chain
      critical metal because of increasing demand, scarcity and irreplaceable for
      technological application. To bring back the neodymium to supply stream the
      recycling of end of life neodymium-bearing waste can be a feasible option. Out of
      total domestic consumption, only 21.9 tons of neodymium have been collected and
      subsequently recycled. From material flow analysis, the requirement for an
      efficient recycling system and element-wise material flow management for these
      REEs in the Republic of Korea were realized and recommended.

PMID- 26210234
TI  - Does post-mastectomy radiotherapy affect the outcome and prevalence of
      complications in immediate DIEP breast reconstruction? A prospective cohort
      study.
AB  - INTRODUCTION: The decision to perform immediate deep inferior epigastric
      perforator (DIEP) flap reconstruction in patients requiring post-mastectomy
      radiation therapy (PMRT) is controversial, and often influenced by the increased
      potential of complications. We assessed the outcome and complications of
      irradiated immediate DIEP-reconstructed flaps in a two-surgeon series in our
      department. METHODS: Data collected prospectively from all patients undergoing
      immediate DIEP reconstruction under the two senior authors' care over 24 months
      were reviewed. Patients receiving previous radiation were excluded. Included
      patients were divided into two groups - requiring or not requiring PMRT. Primary
      outcome measures were fat necrosis, surgery for removal of fat necrosis, volume
      loss requiring surgery, wound complications and flap survival. All patients with
      a clinical diagnosis of post-radiation fat necrosis had an ultrasound scan.
      RESULTS: The series included 112 patients with a total of 156 flaps (44
      bilateral, 68 unilateral). In 61/156 flaps the patients received PMRT (Group A)
      whilst 95/156 did not (Group B). Demographics in both groups were similar.
      Outcomes in PMRT vs. no PMRT, respectively were: fat necrosis 11.5% vs. 6.35% (p
      = 0.199); surgery for removal of fat necrosis 6.6% vs. 4.2% (p = 0.383); volume
      enhancement surgery 4.9% vs. 5.2% (p = 0.617); minor wound healing delay, 3.2%
      vs. 7% (p = 0.433); major wound healing delay 2.5% vs. 5.7% (p = 0.558). 0/61
      flaps were lost in group A and 2/95 in group B. CONCLUSION: Although studies have
      shown the deleterious effects of post-operative radiotherapy on breast free
      flaps, our department offers immediate breast reconstruction with the acceptance
      of the risk/benefit profile. We found no increase in complication rates in
      patients undergoing immediate DIEP reconstruction receiving PMRT, and the outcome
      was not adversely affected. As part of an ongoing study, we do not feel that post
      mastectomy radiotherapy precludes the decision for immediate free-flap breast
      reconstruction.

PMID- 26210235
TI  - Some properties and possible biological role of peptidase inhibitors from the
      entomopathogenic fungus Tolypocladium cylindrosporum.
AB  - The activities of secreted and mycelial inhibitors of proteolytic enzymes from
      fungi of the order Hypocreales have been investigated. Inhibitors of bromelain,
      papain, and trypsin of low molecular mass (about 1 kDa) and a subtilisin
      proteinaceous inhibitor with molecular mass of 45 kDa were revealed in the
      culture liquid of the fungus Tolypocladium cylindrosporum. The subtilisin
      inhibitor from T. cylindrosporum has antibiotic properties, significantly
      decreased the activity of purified bacterial enzymes, and prevented the growth of
      the bacterium Pseudomonas sp. Data suggesting the existence in fungi of the
      Hypocreales order of two pools of peptidase inhibitors have been obtained. 

PMID- 26210236
TI  - Chryseobacterium formosus sp. nov., a bacterium isolated from an ancient tree
      trunk.
AB  - A Gram-reaction-negative, non-motile and rod-shaped bacterium, designated as THG
      DN3.6(T), was isolated from an ancient tree trunk from Republic of Korea. On the
      basis of 16S rRNA gene sequence analysis, strain THG-DN3.6(T) was shown to belong
      to the genus Chryseobacterium and the highest similarity to Chryseobacterium
      indoltheticum LMG 4025(T) (97.2%) and the closest phylogenetic relatives were
      Chryseobacterium scophthalmum (96.8%), Chryseobacterium piscium (96.7%) and
      Chryseobacterium balustinum KCTC 2903(T) (96.3%). The DNA G + C content of the
      isolate was 33.2 mol%. The predominant isoprenoid quinone was menaquinone-6. The
      major fatty acids were iso-C15:0, summed feature 3 (C16:1 omega7c and/or C16:1
      omega7t and/or iso-C15:0 2-OH), iso-C17:1 omega9c and iso-C17:0 3-OH. The major
      polar lipids of strain THG-DN3.6(T) were phosphatidylethanolamine. The mean DNA
      DNA relatedness of strain THG-DN3.6(T) to C. indoltheticum LMG 4025(T) was 52 +/-
      0.5%. Based on the results of polyphasic characterization, strain THG-DN3.6(T)
      represented a novel species within the genus Chryseobacterium, for which the name
      Chryseobacterium formosus sp. nov. is proposed. The type strain is THG-DN3.6(T)
      (=KCTC 42606 = CCTCC AB 2015118). The NCBI GenBank accession number for the 16S
      rRNA gene sequence of strain THG-DN3.6(T) is KM035938.

PMID- 26210237
TI  - Skin diseases associated with Agent Orange and other organochlorine exposures.
AB  - Organochlorine exposure is an important cause of cutaneous and systemic toxicity.
      Exposure has been associated with industrial accidents, intentional poisoning,
      and the use of defoliants, such as Agent Orange in the Vietnam War. Although long
      term health effects are systematically reviewed by the Institute of Medicine,
      skin diseases are not comprehensively assessed. This represents an important
      practice gap as patients can present with cutaneous findings. This article
      provides a systematic review of the cutaneous manifestations of known mass
      organochlorine exposures in military and industrial settings with the goal of
      providing clinically useful recommendations for dermatologists seeing patients
      inquiring about organochlorine effects. Patients with a new diagnosis of
      chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma),
      and soft-tissue sarcomas including dermatofibrosarcoma protuberans and
      leiomyosarcomas should be screened for a history of Vietnam service or industrial
      exposure. Inconclusive evidence exists for an increased risk of other skin
      diseases in Vietnam veterans exposed to Agent Orange including benign fatty
      tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias,
      disturbance of skin sensation, and rashes not otherwise specified. Affected
      veterans should be informed of the uncertain data in those cases. Referral to
      Department of Veterans Affairs for disability assessment is indicated for
      conditions with established associations. 

PMID- 26210238
TI  - Simultaneous analysis of nuclear and mitochondrial DNA, mRNA and miRNA from
      backspatter from inside parts of firearms generated by shots at "triple contrast"
      doped ballistic models.
AB  - When a firearm projectile hits a biological target a spray of biological material
      (e.g., blood and tissue fragments) can be propelled from the entrance wound back
      towards the firearm. This phenomenon has become known as "backspatter" and if
      caused by contact shots or shots from short distances traces of backspatter may
      reach, consolidate on, and be recovered from, the inside surfaces of the firearm.
      Thus, a comprehensive investigation of firearm-related crimes must not only
      comprise of wound ballistic assessment but also backspatter analysis, and may
      even take into account potential correlations between these emergences. The aim
      of the present study was to evaluate and expand the applicability of the "triple
      contrast" method by probing its compatibility with forensic analysis of nuclear
      and mitochondrial DNA and the simultaneous investigation of co-extracted mRNA and
      miRNA from backspatter collected from internal components of different types of
      firearms after experimental shootings. We demonstrate that "triple contrast"
      stained biological samples collected from the inside surfaces of firearms are
      amenable to forensic co-analysis of DNA and RNA and permit sequence analysis of
      the entire mtDNA displacement-loop, even for "low template" DNA amounts that
      preclude standard short tandem repeat DNA analysis. Our findings underscore the
      "triple contrast" method's usefulness as a research tool in experimental forensic
      ballistics. 

PMID- 26210239
TI  - Mercury embolism of the lung and right ventricle revealed by postmortem computed
      tomography and X-ray analytic microscopy.

PMID- 26210240
TI  - KRAS Status as an Independent Prognostic Factor for Survival after Yttrium-90
      Radioembolization Therapy for Unresectable Colorectal Cancer Liver Metastases.
AB  - PURPOSE: To evaluate Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation
      status as a prognostic factor for survival after yttrium-90 ((90)Y)
      radioembolization for colorectal cancer (CRC) liver metastases. MATERIALS AND
      METHODS: Consecutive patients with unresectable CRC liver metastases and
      documented KRAS mutation status who were treated with (90)Y radioembolization
      during the period 2007-2014 were investigated. Patient demographics, disease
      characteristics, therapy regimens, and overall survival (OS) from first (90)Y
      radioembolization were compared between patients with KRAS wild-type (wt) and
      mutant status. Kaplan-Meier estimation and Cox regression were used for survival
      analysis and to assess independent prognostic factors for OS. RESULTS: Of 186
      patients, 104 underwent KRAS mutation analysis before (90)Y radioembolization,
      with 45 (43.3%) identified as mutant. The wt and mutant groups were similar in
      demographics, liver status, overall performance status, and tumor characteristics
      (all P > .05). Mean time from liver metastasis to (90)Y radioembolization was
      greater in patients with KRAS wt status (P = .033). A greater percentage of wt
      patients received anti-epidermal growth factor receptor therapies before (90)Y
      radioembolization (66.1% vs 8.9%; P < .001). Median OS from first (90)Y
      radioembolization was significantly greater in KRAS wt patients (9.5 mo vs 4.8
      mo; P = .041). Univariate analysis identified Child-Pugh class, carcinoembryonic
      antigen (CEA), chemotherapy after (90)Y radioembolization, KRAS status, and
      treatment-induced toxicity as prognostic factors for OS. Multivariate Cox
      regression analysis demonstrated Child-Pugh class, CEA, and KRAS status to be
      independent prognostic factors for OS, even when correcting for the effect of
      chemotherapy after (90)Y radioembolization. CONCLUSIONS: Patients with CRC and
      KRAS wt may derive greater survival benefit from (90)Y radioembolization therapy
      than patients with KRAS mutant.

PMID- 26210241
TI  - A Spinal Cord Radiofrequency Destruction.

PMID- 26210242
TI  - Comprehension Level-Appropriate Patient Educational Content: An Opportunity for
      Interventional Radiologists to Create and Demonstrate Value.

PMID- 26210243
TI  - JVIR Celebrates 25 Years of Innovation. Part 2: 1995-2000.

PMID- 26210244
TI  - Percutaneous Irreversible Electroporation for Recurrent Thyroid Cancer--A Case
      Report.
AB  - A 74-year-old man presented with a small locoregional, histopathologically
      proven, fluorodeoxyglucose positron emission tomography/computed tomography-avid
      recurrence of follicular thyroid carcinoma in the left subglottic space after
      extensive surgical resection, adjuvant radioactive iodine therapy, and external
      beam radiation therapy. Because all established focal therapies were
      contraindicated, percutaneous irreversible electroporation was performed without
      complications. Follow-up imaging at 7 months showed a small ablation scar without
      signs for residual vital tumor tissue. Irreversible electroporation may be a
      viable treatment option for selected cases of recurring head and neck tumors that
      are unsuitable for other local treatments. 

PMID- 26210245
TI  - Breast Foreign Body Extraction Using the Breast Lesion Excision System.

PMID- 26210246
TI  - Preliminary Results in Unresectable Head and Neck Cancer Treated by
      Radiofrequency and Microwave Ablation: Feasibility, Efficacy, and Safety.
AB  - PURPOSE: To retrospectively determine whether the application of thermal ablation
      to recurrent and advanced head and neck cancer (HNC) could allow for local tumor
      control. MATERIALS AND METHODS: From 2002 to 2014, 22 patients (17 men and 5
      women; mean age, 64 y; age range, 42-88 y) with unresectable HNC lesions treated
      with thermal ablation were evaluated. Patients were followed at 3 and 6 months
      after treatment, every 6 months for 5 years, and yearly thereafter with computed
      tomography and/or magnetic resonance imaging. The mean follow-up period was 32.2
      months (range, 3-51 mo). RESULTS: Three of 22 patients with primary lesions are
      still alive; two of these patients were treated with radiofrequency (RF) ablation
      and one was treated with microwave (MW) ablation. Of the 19 remaining patients,
      four were treated with MW ablation and 15 were treated with RF ablation. Imaging
      revealed partial response in eight patients, and complete response was observed
      in the remaining 14. There were two major complications after ablation treatment.
      The mean survival time was 32.9 months +/- 3.205 (standard error; 95% confidence
      interval [CI], 26.6-39.2 mo). The survival time for MW ablation cases (36 mo +/-
      5.185; 95% CI, 25.8-46.16 mo) was longer than for RF ablation (32.2 mo +/- 3.911;
      95% CI, 24.5-39.8 mo), although the CI overlap between the groups is large.
      CONCLUSIONS: Percutaneous thermal ablation is a promising alternative treatment
      for local control of incurable HNC.

PMID- 26210247
TI  - Magnetic Resonance-Monitored Coaxial Electrochemical Ablation--Preliminary
      Evaluation of Technical Feasibility.
AB  - PURPOSE: To evaluate the technical feasibility of a coaxial electrode
      configuration to rapidly create a mechanically defined electrochemical ablation
      zone monitored by magnetic resonance (MR) imaging in real time. MATERIALS AND
      METHODS: A direct current generator supplied the nitinol cathode cage and central
      platinum anode for coaxial electrochemical ablation. Safety and efficacy were
      evaluated by measuring local pH, temperature, and current scatter in saline
      solutions. Ablation zone diameters of 3-6 cm (n = 72) were created on ex vivo
      bovine liver and verified by gross pathology. Feasibility of MR monitoring was
      evaluated using 8 swine livers to create ablations of 3 cm (n = 12), 4 cm (n =
      4), and 5 cm (n = 4) verified by histology. RESULTS: Local pH was 3.2 at the
      anode and 13.8 at the cathode. Current scatter was negligible. Ablation progress
      increased relative to local ion concentration, and MR signal changes corresponded
      to histologic findings. In the ex vivo model, the times to achieve complete
      ablation were 15 minutes, 20 minutes, 35 minutes, and 40 minutes for diameters of
      3 cm, 4 cm, 5 cm, and 6 cm, respectively. Ablation times for the in situ model
      were 15 minutes, 35 minutes, and 50 minutes for 3 cm, 4 cm, and 5 cm,
      respectively. CONCLUSIONS: The coaxial configuration mechanically defined the
      electrochemical ablation zone with times similar to comparably sized thermal
      ablations. MR compatibility allowed for real-time monitoring of ablation
      progress.

PMID- 26210248
TI  - Percutaneous Cryoablation of Scapular Metastasis Associated with Iatrogenic
      Injury to the Suprascapular, Subscapular, and Axillary Nerves.

PMID- 26210249
TI  - Re: "Comparison of Transarterial Chemoembolization and Hepatic Resection for
      Large Solitary Hepatocellular Carcinoma: A Propensity Score Analysis".

PMID- 26210250
TI  - Drs. Lee et al respond.

PMID- 26210251
TI  - Re: Safety and Efficacy of 70-150 um and 100-300 um Drug-Eluting Bead
      Transarterial Chemoembolization for Hepatocellular Carcinoma.

PMID- 26210252
TI  - Drs. Deipolyi et al respond.

PMID- 26210253
TI  - The Role of Public Health in a Global Surgery Fellowship.

PMID- 26210255
TI  - Swollen nerves slimming: Sequential nerve ultrasound in acute Guillain-Barre
      syndrome.

PMID- 26210254
TI  - FOXF2 suppresses the FOXC2-mediated epithelial-mesenchymal transition and
      multidrug resistance of basal-like breast cancer.
AB  - Forkhead box (FOX) F2 and FOXC2 belong to the FOX transcription factor
      superfamily. FOXC2 is recognized as an inducer of epithelial-mesenchymal
      transition (EMT), and its overexpression promotes basal-like breast cancer (BLBC)
      metastasis. Our previous study demonstrated that FOXF2 functions as an EMT
      suppressor and that FOXF2 deficiency promotes BLBC metastasis. However, the
      relationship between the opposite EMT-related transcription factors FOXF2 and
      FOXC2 remains unknown. Here, we found that FOXF2 directly targets FOXC2 to
      negatively regulate FOXC2 transcription in BLBC cells. Functionally, we observed
      that FOXC2 mediates the FOXF2-regulated EMT phenotype, aggressive behavior, and
      multiple chemotherapy drug resistance of BLBC cells. Additionally, we detected a
      significant negative correlation between the FOXF2 and FOXC2 mRNA levels in
      triple-negative breast cancer (TNBC) tissues. TNBC patients in the
      FOXF2high/FOXC2low and FOXF2low/FOXC2high groups exhibited the best and worst
      disease-free survival (DFS), respectively, whereas the patients in the
      FOXF2high/FOXC2high and FOXF2low/FOXC2low groups exhibited moderate DFS. In
      summary, we found that FOXF2 transcriptionally targets FOXC2 and suppresses EMT
      and multidrug resistance by negatively regulating the transcription of FOXC2 in
      BLBC cells. The combined expression levels of FOXF2 and FOXC2 mRNA might serve as
      an effective prognostic indicator and could guide tailored therapy for TNBC or
      BLBC patients. 

PMID- 26210256
TI  - An apparent anti-Hu sensory neuropathy with normal sensory nerve action
      potentials.

PMID- 26210257
TI  - To dispense or not to dispense? Ethical case decision-making in pharmacy
      practice.
AB  - In daily practice, pharmacists are regularly confronted with moral problems in
      which deciding what to do is not always a straightforward decision. In this
      contribution we show how the use of a specific method for moral deliberation can
      (in retrospect or prospective) aid moral judgements. We use the case of
      dispensing isotretinoin to demonstrate one ethical reflection method, namely the
      Utrecht Method. 

PMID- 26210258
TI  - Pharmacists' performance in a telephone-based simulated patient study after a
      mental health capacity-building program.
AB  - BACKGROUND: The More Than Meds program was developed to enhance community
      pharmacy based services for people with mental illness. OBJECTIVE: To evaluate
      the care of pharmacists who participated in this specific program using a
      telephone-based simulated patient with insomnia. METHODS: A trained actor used a
      simulated patient case scenario and telephoned pharmacists (i.e., intervention
      group pharmacists) and a control group of pharmacists approximately 6 months
      following training. Pharmacists were scored on their assessment of the patient
      and problem, guidance provided on both pharmacological and nonpharmacological
      care, communications, and overall quality. RESULTS: Sixty-three pharmacists (n =
      29 intervention, n = 34 controls) were reached. Call duration was longer with
      intervention versus control group pharmacists [4.93 min (SD 2.3) vs. 4.00 min (SD
      1.8)]. Medication recommendations were made by 76 and 100 % of intervention
      versus control pharmacists (p = 0.002), respectively. Intervention group
      pharmacists scored significantly higher on most components within communication
      and overall quality scores. Scores for assessing the patient, the problem, sleep,
      and medication supply were lower than expected for both groups. CONCLUSION:
      Intervention group pharmacists performed better than controls on several
      components of a telephone-based simulated patient scenario for insomnia following
      More Than Meds training. More research is needed regarding telephone
      consultations in pharmacy practice.

PMID- 26210259
TI  - Cathepsins of lepidopteran insects: Aspects and prospects.
AB  - Molecular understanding of lepidopteran physiology has revealed that proteases
      consist of one of the central regulatory/reacting system for insect growth and
      survival. Among the various proteases, cathepsins are the most crucial cellular
      proteases, which play vital roles during insect development. In the present
      review, we have discussed various aspects of the lepidopteran insect cathepsins,
      emphasizing their roles in processes like development, growth, metamorphosis,
      apoptosis and immunity. Cathepsins are categorized into different types on the
      basis of their sequence diversification, leading to variation in structure and
      catalytic function. Cathepsins exhibit tissue and stage specific expression
      pattern which is fine-tuned by a delicate balance of expression,
      compartmentalization, zymogen activation, inhibition by protein inhibitors and
      degradation. The indispensability of cathepsins as cellular proteases in the
      above mentioned processes proposes them as novel targets for designing effective
      and specific insect controlling strategies. 

PMID- 26210260
TI  - Development of a new pCAMBIA binary vector using Gateway(r) technology.
AB  - pCAMBIA vectors have become popular for their easy handling, stability and the
      existence of a range of selection and reporter genes. However, these vectors have
      yet to integrate the Gateway(r) cloning system, which has enabled site-specific
      recombination without the need for restriction enzymes and ligases. This paper
      sets out to convert the pCambia2300 binary vector into a destination vector with
      the Gateway(r) cassette driven by the CaMV35S promoter. The destination vector,
      pCamway35S, was then evaluated using the uidA reporter gene. Transient and stable
      transformation experiments were successfully assayed, either by particle
      bombardment or by Agrobacterium tumefaciens in Allium cepa and Hevea embryogenic
      calli. After counting the transformation units, the statistical analysis
      performed on the data showed that the pCamway 35S::uidA vector was as efficient
      as pCambia2301, a pCAMBIA2300 containing the uidA reporter gene under the CaMV
      35S promoter. 

PMID- 26210261
TI  - Transcatheter aortic valve implantation in nonagenarians: Looking beyond
      survival.

PMID- 26210262
TI  - A porcine model for aortic valve insufficiency: If pigs could fly, they would
      teach surgeons to treat AI.

PMID- 26210263
TI  - An aggressive, novel approach using a vacuum-assisted system to treat thoracic
      aortic graft infection.

PMID- 26210264
TI  - Not so bad ... but not as good as we would like.

PMID- 26210265
TI  - Sutureless aortic valve replacement in patients who have bicuspid aortic valve.
AB  - OBJECTIVE: Bicuspid aortic valve (BAV) is generally considered to be a
      contraindication to sutureless aortic valve replacement (AVR). The aim of this
      study was to evaluate the feasibility and perioperative outcomes of this
      technique in patients with BAV. METHODS: From June 2011 to January 2014, a total
      of 25 patients who underwent sutureless AVR had documented BAV. Thirteen patients
      (52%) had median sternotomy, and 12 patients (48%) a minimally invasive approach.
      RESULTS: The study population included 17 (68%) men with a median age of 77.8 +/-
      5.4 years. The mean EuroSCORE II was 3.4% +/- 2.6%. Concomitant procedures
      included coronary artery bypass grafting in 8 patients (32%), 2 AVRs (8%), 1
      mitral valve repair (4%), 1 septal myomectomy (4%), and 1 atrial septal defect
      closure (4%). The mean transaortic valve gradient decreased from 49.4 +/- 15.7,
      to 14.5 +/- 5.4 mm Hg postoperatively. The mean aortic valve area increased from
      0.78 +/- 0.18, to 1.75 +/- 0.43 cm(2) postoperatively. Five patients (20%)
      suffered from atrioventricular block that required permanent pacemaker
      implantation. Two patients (8%) suffered a stroke. No major paravalvular leakage
      occurred, and no postoperative valve migration. In-hospital mortality occurred in
      1 patient (4%). The mean intensive care unit length of stay was 3 +/- 2 days
      postoperatively. CONCLUSIONS: This study demonstrates that a sutureless aortic
      valve can be deployed in patients with BAV without increasing the risk of
      paravalvular leakage. BAV should not be considered a contraindication to
      sutureless AVR.

PMID- 26210266
TI  - Treating valvular heart disease has never been one size fits all.

PMID- 26210267
TI  - Heart transplantation in patients who have congenital heart disease and single
      lung physiology.

PMID- 26210268
TI  - Treatment of MDR-Gram negative infections in the 21st century: a never ending
      threat for clinicians.
AB  - The spread of antimicrobial resistance among Gram negative bacteria has
      dramatically reduced the current therapeutic opportunities and hampered the
      perspectives of drug discovery pipeline. Several unmet needs concerning the
      optimal therapeutic approaches to severe infections caused by the leading multi
      drug-resistant GNB are still unresolved, mainly in relationship with the
      difficulty in the design of prospective comparative studies. Therefore a
      perspective of how the main resistance patterns and the related infections can be
      managed in the absence of more definitive data is mandatory. 

PMID- 26210269
TI  - Visible and near-infrared bulk optical properties of raw milk.
AB  - The implementation of optical sensor technology to monitor the milk quality on
      dairy farms and milk processing plants would support the early detection of
      altering production processes. Basic visible and near-infrared spectroscopy is
      already widely used to measure the composition of agricultural and food products.
      However, to obtain maximal performance, the design of such optical sensors should
      be optimized with regard to the optical properties of the samples to be measured.
      Therefore, the aim of this study was to determine the visible and near-infrared
      bulk absorption coefficient, bulk scattering coefficient, and scattering
      anisotropy spectra for a diverse set of raw milk samples originating from
      individual cow milkings, representing the milk variability present on dairy
      farms. Accordingly, this database of bulk optical properties can be used in
      future simulation studies to efficiently optimize and validate the design of an
      optical milk quality sensor. In a next step of the current study, the relation
      between the obtained bulk optical properties and milk quality properties was
      analyzed in detail. The bulk absorption coefficient spectra were found to mainly
      contain information on the water, fat, and casein content, whereas the bulk
      scattering coefficient spectra were found to be primarily influenced by the
      quantity and the size of the fat globules. Moreover, a strong positive
      correlation (r >= 0.975) was found between the fat content in raw milk and the
      measured bulk scattering coefficients in the 1,300 to 1,400 nm wavelength range.
      Relative to the bulk scattering coefficient, the variability on the scattering
      anisotropy factor was found to be limited. This is because the milk scattering
      anisotropy is nearly independent of the fat globule and casein micelle quantity,
      while it is mainly determined by the size of the fat globules. As this study
      shows high correlations between the sample's bulk optical properties and the milk
      composition and fat globule size, a sensor that allows for robust separation
      between the absorption and scattering properties would enable accurate prediction
      of the raw milk quality parameters.

PMID- 26210270
TI  - Randomized clinical trial of intrauterine cephapirin infusion in dairy cows for
      the treatment of purulent vaginal discharge and cytological endometritis.
AB  - The objectives of this study were to quantify the effect of an intrauterine
      infusion of cephapirin on reproductive performance at first service of postpartum
      dairy cows affected by purulent vaginal discharge (PVD) and cytological
      endometritis (ENDO) using different diagnostic strategies, and to determine if
      the presence of prolonged anovulation would influence the magnitude of treatment
      benefit. In total, 2,259 Holstein cows in 28 herds were enrolled in a randomized
      clinical trial. At 35 (+/- 7) days in milk (DIM), cows were diagnosed with PVD
      using the Metricheck device (Simcro, Hamilton, New Zealand), with cytological
      endometritis using endometrial cytology (ENDO-CYTO), and with cytological
      endometritis using leukocyte esterase (ENDO-LE). Regardless of reproductive tract
      disease status, cows were randomly assigned to receive an intrauterine cephapirin
      infusion or to not be treated. Serum progesterone was measured at 35 and 49 (+/-
      7) DIM (14 d apart); cows were considered to have prolonged anovulation if
      progesterone was <1 ng/mL at both times. Reproductive events of cows were
      collected until 200 DIM. Statistical analyses were conducted using multivariable
      mixed logistic regression models. Intrauterine cephapirin treatment was
      associated with an increased first-service pregnancy risk in cows diagnosed with
      PVD (no treatment: 15.4%; treatment: 31.4%), ENDO-CYTO (no treatment: 16.2%,
      treatment: 24.4%), and ENDO-LE (no treatment: 15.8%; treatment: 25.1%), but not
      in cows unaffected by any form of reproductive tract disease (no treatment:
      34.8%; treatment: 32.6%). Cephapirin treatment was also associated with an
      increased first-service reproductive performance in cows affected simultaneously
      by both PVD and ENDO-CYTO (no treatment: 8.7%; treatment: 23.4%). The effect of
      cephapirin treatment in anovular cows (no treatment: 21.0%; treatment: 26.4%) was
      numerically lower than in cyclic cows (no treatment: 22.7%; treatment: 34.1%).
      Overall, an intrauterine infusion of cephapirin improved first-service pregnancy
      risk in cows with postpartum reproductive tract disease and this effect was
      influenced by postpartum anovulation status.

PMID- 26210271
TI  - Effects of prepartum fat supplementation on plasma concentrations of glucagon
      like peptide-1, peptide YY, adropin, insulin, and leptin in periparturient dairy
      cows.
AB  - Dietary fat supplementation during the periparturient period is one strategy to
      increase energy intake and attenuate the degree of negative energy balance during
      early lactation; however, little is known of the underlying hormonal and
      metabolic adaptations. We evaluated the effects of prepartum fat supplementation
      on energy-balance parameters and plasma concentrations of glucagon-like peptide
      1, peptide tyrosine-tyrosine (PYY), adropin, insulin, leptin, glucose,
      nonesterified fatty acid, and beta-hydroxybutyric acid in dairy cows. Twenty-four
      pregnant dairy cows were randomized to diets containing either rolled canola or
      sunflower seed at 8% of dry matter, or no oilseed supplementation, during the
      last 5 wk of gestation and then assigned to a common lactation diet postpartum.
      Blood samples were collected at -2, +2, and +14 h relative to feeding, at 2 wk
      after the initiation of the diets, and at 2 wk postpartum. Dietary canola and
      sunflower supplementation alone did not affect energy balance, body weight, and
      plasma concentrations of glucagon-like peptide-1, PYY, adropin, insulin, leptin,
      nonesterified fatty acid, and beta-hydroxybutyric acid; however, canola decreased
      and sunflower tended to decrease dry matter intake. We also observed that the
      physiological stage had a significant, but divergent, effect on circulating
      hormones and metabolite concentrations. Plasma glucagon-like peptide-1, PYY,
      adropin, nonesterified fatty acid, and beta-hydroxybutyric acid concentrations
      were greater postpartum than prepartum, whereas glucose, insulin, leptin, body
      weight, and energy balance were greater prepartum than postpartum. Furthermore,
      the interaction of treatment and stage was significant for leptin and adropin,
      and tended toward significance for PYY and insulin; only insulin exhibited an
      apparent postprandial increase. Postpartum PYY concentrations exhibited a strong
      negative correlation with body weight, suggesting that PYY may be associated with
      body weight regulation during the transition period. These novel findings
      demonstrate that the transition from pregnancy to lactation is a stronger
      determinant of circulating gut hormone concentrations than dietary lipid in
      transition dairy cows. 

PMID- 26210272
TI  - Feed intake is related to changes in plasma nonesterified fatty acid
      concentration and hepatic acetyl CoA content following feeding in lactating dairy
      cows.
AB  - The relationship between hepatic acetyl CoA (AcCoA) content and dry matter intake
      (DMI) was evaluated using 28 multiparous Holstein cows; 14 were early postpartum
      (PP; 12.6 +/- 3.8 d in milk) and 14 were late-lactation cows (LL; 269 +/- 30 d in
      milk). Cows were fed once daily, and DMI was determined for the first 4h after
      feeding. Liver and blood samples were collected before feeding and 4h after
      feeding. Feed intake over the 4-h period ranged from 3.7 to 9.6 kg of dry matter
      and was similar for the 2 stages of lactation. Before feeding, hepatic AcCoA
      content was greater for PP compared with LL cows (34.4 vs. 12.5 nmol/g), and
      decreased over the 4h after feeding for PP only (28.7 vs. 34.4 nmol/g). The range
      for change in AcCoA over the 4-h period was wide for both PP (-24.3 to 10.4
      nmol/g) and LL (-5.7 to 16.1 nmol/g), and was related negatively to DMI at 4h for
      both PP (R(2) = 0.55) and LL (R(2) = 0.31). The reduction in plasma NEFA
      concentration over the 4-h period was greater for PP than LL cows (-681 vs. -47
      uEq/L), and was related to DMI at 4h for both PP and LL (both R(2) = 0.38).
      Greater DMI among cows over the first 4h after feeding might have been from a
      sharper reduction in supply of AcCoA in the liver for oxidation during meals
      because of the reduction in plasma NEFA concentration. Consistent with this is
      that the change in AcCoA was positively related to the reduction in plasma NEFA
      concentration for PP cows (R(2) = 0.31). However, change in plasma NEFA
      concentration was not related to change in hepatic AcCoA in LL cows, indicating
      that the pool of AcCoA in LL cows is not as dependent on NEFA flux to the liver
      as that of PP cows. Further research is required to determine production and fate
      of AcCoA within the timeframe of meals and the effects of feeding on energy
      charge in hepatic tissue.

PMID- 26210274
TI  - An alternative approach to modeling genetic merit of feed efficiency in dairy
      cattle.
AB  - Genetic improvement of feed efficiency (FE) in dairy cattle requires greater
      attention given increasingly important resource constraint issues. A widely
      accepted yet occasionally contested measure of FE in dairy cattle is residual
      feed intake (RFI). The use of RFI is limiting for several reasons, including
      interpretation, differences in recording frequencies between the various
      component traits that define RFI, and potential differences in genetic versus
      nongenetic relationships between dry matter intake (DMI) and FE component traits.
      Hence, analyses focusing on DMI as the response are often preferred. We propose
      an alternative multiple-trait (MT) modeling strategy that exploits the Cholesky
      decomposition to provide a potentially more robust measure of FE. We demonstrate
      that our proposed FE measure is identical to RFI provided that genetic and
      nongenetic relationships between DMI and component traits of FE are identical. We
      assessed both approaches (MT and RFI) by simulation as well as by application to
      26,383 weekly records from 50 to 200 d in milk on 2,470 cows from a dairy FE
      consortium study involving 7 institutions. Although the proposed MT model fared
      better than the RFI model when simulated genetic and nongenetic associations
      between DMI and FE component traits were substantially different from each other,
      no meaningful differences were found in predictive performance between the 2
      models when applied to the consortium data. 

PMID- 26210273
TI  - Intestinal permeability and incidence of diarrhea in newborn calves.
AB  - Seventy-six newborn Holstein calves (44.4 +/- 6.15 kg of body weight) were
      involved in this study from birth until 21 d of age. Within 2 h after birth,
      calves received 4 L of maternal colostrum via an esophageal tube. The following 3
      meals consisted of 2 L of late colostrum (or transition milk). After that, calves
      were fed 1.5 L of milk replacer (22.9% CP, 20.1% fat) twice daily. Calves were
      considered diarrheic when they showed fecal scores >= 3 for 3 consecutive days.
      Then, data from a random subset of 30 calves (45.9 +/- 5.47 kg of body weight),
      15 that never had diarrhea and 15 that had diarrhea, were used to assess
      potential associations between intestinal permeability and incidence of diarrhea.
      On d 0, 7, 14, and 21 of life, intestinal permeability of calves was measured by
      dosing 2 markers (lactulose and d-mannitol) and assessing their concentration in
      serum by ultra-HPLC-mass spectrometry. Plasma IgG concentration was measured at
      birth and at 6 h, 24 h, and 12 d after first colostrum intake, and efficiency of
      IgG absorption was calculated. Plasma and colostrum IgG contents were determined
      by radial immunodiffusion and bacterial load in colostrum samples by colony
      counting. All diarrhea incidences occurred between 7 to 14 d of life. Overall
      colostrum quality was good, with an IgG content > 100mg/mL, but total bacterial
      load was slightly high (> 100,000 cfu/mL). However, there were no differences in
      these 2 parameters between colostrums consumed by calves that did and those that
      did not incur diarrhea later in life, and efficiency of IgG transfer from
      colostrum to bloodstream was similar for all calves. Diarrheic calves had greater
      serum lactulose concentrations than healthy calves throughout the first 21 d of
      life. Furthermore, diarrheic calves tended to have a greater serum lactulose-to-d
      mannitol ratio from birth until 21 d of life compared with healthy calves. In
      conclusion, calves that incur diarrhea show an altered intestinal permeability
      within the first 2 h of life compared with those that do not suffer scours.

PMID- 26210275
TI  - Tocopherols and tocotrienols in serum and liver of dairy cows receiving
      conjugated linoleic acids or a control fat supplement during early lactation.
AB  - The fat-soluble vitamin E comprises the 8 structurally related compounds
      (congeners) alpha-, beta-, gamma-, and delta-tocopherol (with a saturated side
      chain) and alpha-, beta-, gamma-, and delta-tocotrienol (with a 3-fold
      unsaturated side chain). Little is known regarding the blood and liver
      concentrations of the 8 vitamin E congeners during the transition from pregnancy
      to lactation in dairy cows. We thus quantified tocopherols (T) and tocotrienols
      (T3) in serum and liver and hepatic expression of genes involved in vitamin E
      metabolism in pluriparous German Holstein cows during late gestation and early
      lactation and investigated whether dietary supplementation (from d 1 in milk)
      with conjugated linoleic acids (CLA; 100g/d; each 12% of trans-10,cis-12 and cis
      9,trans-11 CLA; n=11) altered these compared with control-fat supplemented cows
      (CTR; n=10). Blood samples and liver biopsies were collected on d -21, 1, 21, 70,
      and 105 (liver only) relative to calving. In both groups, the serum
      concentrations of alphaT, gammaT, betaT3, and deltaT3 increased from d -21 to d
      21 and remained unchanged between d 21 and 70, but were unaffected by CLA. The
      concentrations of the different congeners of vitamin E in liver did not differ
      between the CTR and the CLA groups. In both groups, the concentrations of the
      vitamin E forms in liver changed during the course of the study. The hepatic mRNA
      abundance of genes controlling vitamin E status did not differ between groups,
      but alpha-tocopherol transfer protein and tocopherol-associated protein mRNA
      increased with time of lactation in both. In conclusion, the concentrations of
      vitamin E congeners and the expression of genes related to vitamin E status
      follow characteristic time-related changes during the transition from late
      gestation to early lactation but are unaffected by CLA supplementation at the
      dosage used. 

PMID- 26210276
TI  - Amaltheys: A fluorescence-based analyzer to assess cheese milk denatured whey
      proteins.
AB  - The cheese industry faces many challenges to optimize cheese yield and quality. A
      very precise standardization of the cheese milk is needed, which is achieved by a
      fine control of the process and milk composition. Thorough analysis of protein
      composition is important to determine the amount of protein that will be retained
      in the curd or lost in the whey. The fluorescence-based Amaltheys analyzer
      (Spectralys Innovation, Romainville, France) was developed to assess pH 4.6
      soluble heat-sensitive whey proteins (sWP*) in 5 min. These proteins are those
      that can be denatured upon heat-treatment and further retained in the curd after
      coagulation. Monitoring of sWP* in milk and subsequent adaptation of the process
      is a reliable solution to achieve stable cheese yield and quality. Performance of
      the method was evaluated by an accredited laboratory on a 0 to 7 g/L range.
      Accuracy compared with the reference Kjeldahl method is also provided with a
      standard error of 0.25 g/L. Finally, a 4-mo industrial trial in a cheese plant is
      described, where Amaltheys was used as a process analytical technology to monitor
      sWP* content in ingredients and final cheese milk. Calibration models over
      quality parameters of final cheese were also built from near-infrared and
      fluorescence spectroscopic data. The Amaltheys analyzer was found to be a rapid,
      compact, and accurate device to help implementation of standardization procedures
      in the dairy industry. 

PMID- 26210277
TI  - Diets rich in starch improve the efficiency of amino acids use by the mammary
      gland in lactating Jersey cows.
AB  - The objective of this study was to test whether the greater milk N yield usually
      observed when feeding diets based on starch versus fiber was the consequence of a
      higher efficiency of AA use across the mammary gland and whether this effect
      depended on dietary crude protein (CP) content. Five midlactation
      multicatheterized Jersey cows were fed 4 isoenergetic diets to provide 2
      different carbohydrate compositions (CHO; rich in starch vs. rich in fiber)
      crossed by 2 different protein levels (12.0 vs. 16.5% CP) and according to a 4 *
      4 Latin square design. Blood samples were collected at the end of each treatment
      period from the mesenteric artery and mammary vein to determine mammary net
      nutrient fluxes. The nature of nutrients taken up by the mammary gland differed
      between starch and fiber diets: mammary net uptake of acetate increased with
      fiber versus starch diets, whereas mammary net uptake and clearance rate of
      glucose increased with starch versus fiber diets but only at a normal CP level.
      In addition, the mammary net uptake of total, essential, and branched-chain AA
      (BCAA) was significantly enhanced (12, 11, and 26% on average, respectively) when
      feeding starch versus fiber diets, in line with a greater milk protein yield (7%
      on average) and regardless of the CP level. The conversion efficiency of plasma
      essential AA into milk protein was improved with starch diets (33.7% on average)
      compared with fiber diets (27.5% on average). This higher mammary efficiency use
      of AA with starch diets was accompanied by a greater fractional extraction and
      clearance rate of AA belonging to group 2 (BCAA, Lys, Thr) by the mammary gland
      in absence of effects of CHO on either the mammary blood flow or the mammary AA
      metabolism. The positive effect of starch diets on mammary clearance rate and
      uptake of BCAA observed in this study was further improved when increasing
      dietary CP from 12.0 to 16.5%. Concerning the individual AA, Leu was the only
      whose mammary uptake accounted for a higher proportion of total essential AA in
      diets based on starch versus fiber and whose mammary uptake to milk output ratio
      was modified (together with Pro). Diets rich in starch versus fiber improved the
      mammary AA utilization; however, some CHO * CP interactions on mammary metabolism
      support the concept of different metabolic pathways by which starch diets improve
      milk protein yield at the 2 studied CP levels. Results from this study suggest
      that mammary Leu and glucose metabolism can be modulated by the supply of
      glucogenic nutrients to the mammary gland.

PMID- 26210278
TI  - Determination of optimal diagnostic criteria for purulent vaginal discharge and
      cytological endometritis in dairy cows.
AB  - The objectives of this observational study were to identify the optimal
      diagnostic criteria for purulent vaginal discharge (PVD) and cytological
      endometritis (ENDO) using vaginal discharge, endometrial cytology, and leukocyte
      esterase (LE) tests, and to quantify their effect on subsequent reproductive
      performance. Data generated from 1,099 untreated Holstein cows (28 herds)
      enrolled in a randomized clinical trial were used in this study. Cows were
      examined at 35 (+/- 7) d in milk for PVD using vaginal discharge scoring and for
      ENDO using endometrial cytology and LE testing. Optimal combinations of
      diagnostic criteria were determined based on the lowest Akaike information
      criterion (AIC) to predict pregnancy status at first service. Once identified,
      these criteria were used to quantify the effect of PVD and ENDO on pregnancy risk
      at first service and on pregnancy hazard until 200 d in milk (survival analysis).
      Predicting ability of these diagnostic criteria was determined using area under
      the curve (AUC) values. The prevalence of PVD and ENDO was calculated as well as
      the agreement between endometrial cytology and LE. The optimal diagnostic
      criteria (lowest AIC) identified in this study were purulent vaginal discharge or
      worse (>= 4), >= 6% polymorphonuclear leukocytes (PMNL) by endometrial cytology,
      and small amounts of leukocytes or worse (>= 1) by LE testing. When using the
      combination of vaginal discharge and PMNL percentage as diagnostic tools (n =
      1,099), the prevalences of PVD and ENDO were 17.1 and 36.2%, respectively. When
      using the combination of vaginal discharge and LE (n = 915), the prevalences of
      PVD and ENDO were 17.1 and 48.4%. The optimal strategies for predicting pregnancy
      status at first service were the use of LE only (AUC = 0.578) and PMNL percentage
      only (AUC = 0.575). Cows affected by PVD and ENDO had 0.36 and 0.32 times the
      odds, respectively, of being pregnant at first service when using PMNL percentage
      compared with that of unaffected cows; odds ratios were 0.33 and 0.69 for PVD and
      ENDO, respectively, when LE was used. Kappa value (agreement) of the pairwise
      comparison for the PMNL percentage and LE was 0.43. Vaginal discharge,
      endometrial cytology, and LE can be used to diagnose PVD and ENDO, and to predict
      pregnancy status at first service. The use of LE could be a good alternative to
      endometrial cytology for on-farm testing.

PMID- 26210279
TI  - Invited review: Inflammation during the transition to lactation: New adventures
      with an old flame.
AB  - For dairy cattle, the first several weeks of lactation represent the highest-risk
      period in their lives after their own neonatal period. Although more than 50% of
      cows during this period are estimated to suffer from at least one subclinical
      disorder, the complicated admixture of normal adaptations to lactation,
      infectious challenges, and metabolic disorders has made it difficult to determine
      which physiological processes are adaptive and which are pathological during this
      time. Subacute inflammation, a condition that has been well documented in
      obesity, has been a subject of great interest among dairy cattle physiologists in
      the past decade. Many studies have now clearly shown that essentially all cows
      experience some degree of systemic inflammation in the several days after
      parturition. The magnitude and likely persistence of the inflammatory state
      varies widely among cows, and several studies have linked the degree of
      postpartum inflammation to increased disease risk and decreased whole-lactation
      milk production. In addition to these associations, enhancing postpartum
      inflammation with repeated subacute administration of cytokines has impaired
      productivity and markers of health, whereas targeted use of nonsteroidal anti
      inflammatory drugs during this window of time has enhanced whole-lactation
      productivity in several studies. Despite these findings, many questions remain
      about postpartum inflammation, including which organs are key initiators of this
      state and what signaling molecules are responsible for systemic and tissue
      specific inflammatory states. Continued in vivo work should help clarify the
      degree to which mild postpartum inflammation is adaptive and whether the targeted
      use of anti-inflammatory drugs or nutrients can improve the health and
      productivity of dairy cows. 

PMID- 26210280
TI  - Effects of replacing wild rye, corn silage, or corn grain with CaO-treated corn
      stover and dried distillers grains with solubles in lactating cow diets on
      performance, digestibility, and profitability.
AB  - The objective of this study was to measure the effects of partially replacing
      wild rye (Leymus chinensis; WR), corn silage (CS), or corn grain (CG) in dairy
      cow diets with CaO-treated corn stover (T-CS) and corn dried distillers grains
      with soluble (DDGS) on performance, digestibility, blood metabolites, and income
      over feed cost. Thirty tonnes of air-dried corn stover was collected, ground, and
      mixed with 5% CaO. Sixty-four Holstein dairy cows were blocked based on days in
      milk, milk yield, and parity and were randomly assigned to 1 of 4 treatments. The
      treatments were (1) a diet containing 50% concentrate, 15% WR, 25% CS, and 10%
      alfalfa hay (CON); (2) 15% WR, 5% CG, and 6% soybean meal were replaced by 15% T
      CS and 12% DDGS (RWR); (3) 12.5% CS, 6% CG, and 5% soybean meal were replaced by
      12.5% T-CS and 12%DDGS (RCS); (4) 13% CG and 6% soybean meal were replaced by 7%
      T-CS and 13% DDGS (RCG). Compared with CON treatment, cows fed RCS and RCG diets
      had similar dry matter intake (CON: 18.2 +/- 0.31 kg, RCS: 18.6 +/- 0.31 kg, and
      RCG: 18.4 +/- 0.40 kg). The RWR treatment tended to have lower dry matter intake
      than other treatments. The inclusion of T-CS and DDGS in treatment diets as a
      substitute for WR, CS, or CG had no effects on lactose percentage (CON: 4.96 +/-
      0.02%, RWR: 4.97 +/- 0.02%, RCS: 4.96 +/- 0.02%, and RCG: 4.94 +/- 0.02%), 4% fat
      corrected milk yield (CON: 22.7 +/- 0.60 kg, RWR: 22.1 +/- 0.60 kg, RCS: 22.7 +/-
      0.60 kg, and RCG: 22.7 +/- 0.60 kg), milk fat yield (CON: 0.90 +/- 0.03 kg, RWR:
      0.86 +/- 0.03 kg, RCS: 0.87 +/- 0.03 kg, and RCG: 0.89 +/- 0.03 kg), and milk
      protein yield (CON: 0.74 +/- 0.02 kg, RWR: 0.72 +/- 0.02 kg, RCS: 0.73 +/- 0.02
      kg, and RCG: 0.71 +/- 0.02 kg). Cows fed the RWR diet had higher apparent dry
      matter digestibility (73.7 +/- 1.30 vs. 70.2 +/- 1.15, 69.9 +/- 1.15, and 69.9 +/
      1.15% for RWR vs. CON, RCS, and RCG, respectively) and lower serum urea N (3.55
      +/- 0.11 vs. 4.03 +/- 0.11, 3.95 +/- 0.11, and 3.99 +/- 0.11 mmol/L for RWR vs.
      CON, RCS, and RCG, respectively) than cows fed other diets. No significant
      differences were noted in apparent neutral detergent fiber digestibility among
      the treatments. Compared with CON treatment, the RWR, RCS, and RCG treatments
      generated an additional $0.77, $0.70, and $0.81 income over feed cost per cow per
      day, respectively. In conclusion, feeding diets containing a portion of T-CS and
      DDGS can improve profitability of the treatment groups without negatively
      affecting the lactation performance of mid- to late-lactation cows.

PMID- 26210281
TI  - Mortality Predictors in Patients Referred for but Not Undergoing Transcatheter
      Aortic Valve Replacement.
AB  - Although transcatheter aortic valve replacement (TAVR) has expanded the
      proportion of patients with aortic stenosis (AS) who are candidates for valve
      replacement, some patients remain untreated, and their outcomes are not clear. We
      evaluated 172 consecutive patients with severe symptomatic AS referred for TAVR
      who declined (n = 55) or were not candidates for (n = 117) intervention. We
      examined clinical and echocardiographic variables associated with mortality.
      There were 77 deaths, and mean follow-up was 17.9 +/- 10.9 months for survivors.
      Mortality rate at 1 and 2 years was 39.2% and 52.6%, respectively. There was a
      significant difference in mortality rate between patients who declined the
      procedure and those who were not candidates (p = 0.001), with 1-year mortality
      rates of 20.6% and 48.4%, respectively. On multivariate analysis, 4 variables
      were independently associated with all-cause mortality: New York Heart
      Association Class IV heart failure (hazard ratio [HR] 2.6, 95% confidence
      interval [CI] 1.6 to 4.2, p <0.001), glomerular filtration rate <48 ml/min (HR
      2.1, 95% CI 1.3 to 3.4, p = 0.002), albumin <3.9 g/dl (HR 1.9, 95% CI 1.2 to 3.1,
      p = 0.007), and ejection fraction <50% (HR 1.9, 95% CI 1.4 to 3.0, p = 0.01). In
      this new era with expanded treatment options, patients with severe symptomatic AS
      who remain untreated after referral for TAVR experience a mortality rate of 39%
      at 1 year. The presence of advanced heart failure, renal dysfunction, low
      albumin, and/or left ventricular dysfunction identifies patients at higher risk
      of mortality.

PMID- 26210282
TI  - BEST-When a Study Falls Short of Its Acronym.

PMID- 26210283
TI  - Blood compatibility of magnesium and its alloys.
AB  - RATIONALE: Blood compatibility analysis in the field of biomaterials is a highly
      controversial topic. Especially for degradable materials like magnesium and its
      alloys no established test methods are available. OBJECTIVE: The purpose of this
      study was to apply advanced test methodology for the analysis of degrading
      materials to get a mechanistic insight into the corrosion process in contact with
      human blood and plasma. METHODS AND RESULTS: Pure magnesium and two magnesium
      alloys were analysed in a modified Chandler-Loop setup. Standard clinical
      parameters were determined, and a thorough analysis of the resulting implant
      surface chemistry was performed. The contact of the materials to blood evoked an
      accelerated inflammatory and cell-induced osteoconductive reaction. Corrosion
      products formed indicate a more realistic, in vivo like situation. CONCLUSIONS:
      The active regulation of corrosion mechanisms of magnesium alloys by different
      cell types should be more in the focus of research to bridge the gap between in
      vitro and in vivo observations and to understand the mechanism of action. This in
      turn could lead to a better acceptance of these materials for implant
      applications. STATEMENT OF SIGNIFICANCE: The presented study deals with the first
      mechanistic insights during whole human blood contact and its influence on a
      degrading magnesium-based biomaterial. The combination of clinical parameters and
      corrosion layer analysis has been performed for the first time. It could be of
      interest due to the intended use of magnesium-based stents and for orthopaedic
      applications for clinical applications. An interest for the readers of Acta
      Biomaterialia may be given, as one of the first clinically approved magnesium
      based devices is a wound-closure device, which is in direct contact with blood.
      Moreover, for orthopaedic applications also blood contact is of high interest.
      Although this is not the focus of the manuscript, it could help to rise awareness
      for potential future applications.

PMID- 26210284
TI  - Efficacy of a novel antimicrobial peptide against periodontal pathogens in both
      planktonic and polymicrobial biofilm states.
AB  - Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis
      represent the early, middle and late colonizers of the bacterial accretion in
      dental plaque biofilms. These sessile communities constitute a protected mode of
      growth that promotes survival in a hostile environment. This study describes a
      novel and unrecognized role for a synthetic cationic antimicrobial peptide, Nal-P
      113, which inhibits and kills periodontal bacteria in planktonic state, inhibits
      the formation of biofilms and eradicates polymicrobial biofilms. Nal-P-113 is
      also stable in saliva, serum and saline solution. At a concentration less than
      320 MUg/mL which is harmless to normal oral cells, Nal-P-113 can kill bacteria in
      planktonic state. At a concentration of antimicrobial peptide Nal-P-113 (1280
      MUg/mL) which only causes slight damages to normal oral cells is needed to kill
      bacteria in biofilm state. It is worth mentioning that this concentration of Nal
      P-113 is harmless to rat oral mucosa compared to chlorhexidine. The mechanism of
      Nal-P-113 inhibiting and killing periodontal bacteria might rely on the abilities
      to permeabilize and/or to form pores within the cytoplasmic membranes, thus
      causes the death of bacteria. Here, we provided a novel and stable antimicrobial
      peptide with very low mammalian cytotoxicity, which can inhibit and kill
      periodontal bacteria in both planktonic and polymicrobial biofilm states.
      STATEMENT OF SIGNIFICANCE: Nal-P-113 is a potent antimicrobial peptide with
      strong antimicrobial ability, improved deficiency compared with other
      antibacterial peptides, and remains stable in phosphate buffered saline, saliva,
      brain-heart infusion medium and bovine calf serum. Nal-P-113 exhibits a broad
      spectrum of bacteriocidal activity with excellent eradicating capability on oral
      pathogens and the respective biofilms. In this study, we used propidium iodide
      staining, scanning electron microscopy and transmission electron microscopy to
      confirm that Nal-P-113 can perforate plasmalemma thereby resulting in the death
      of oral pathogens and disintegrate the respective biofilms. Nal-P-113 also showed
      effective anti-plaque biofilms and cytotoxicity in the rat periodontitis model.
      No adverse effects can be observed on the gingivomucosa tissue. In short, the
      antimicrobial peptide Nal-P-113 presented to be an effective yet have low
      mammalian cytotoxicity agent with potential application in the clinic. This study
      provides a proof of concept in applying antimicrobial peptides in the clinical
      perspective.

PMID- 26210285
TI  - A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical
      properties in bioprinted tissue constructs.
AB  - Advancement of bioprinting technology is limited by the availability of materials
      that both facilitate bioprinting logistics as well as support cell viability and
      function by providing tissue-specific cues. Herein we describe a modular
      hyaluronic acid (HA) and gelatin-based hydrogel toolbox comprised of a 2
      crosslinker, 2-stage polymerization technique, and the capability to provide
      tissue specific biochemically and mechanically accurate signals to cells within
      biofabricated tissue constructs. First, we prepared and characterized several
      tissue-derived decellularized extracellular matrix-based solutions, which contain
      complex combinations of growth factors, collagens, glycosaminoglycans, and
      elastin. These solutions can be incorporated into bioinks to provide the
      important biochemical cues of different tissue types. Second, we employed
      combinations of PEG-based crosslinkers with varying molecular weights, geometries
      (linear, 4-arm, and 8-arm), and functional groups to yield hydrogel bioinks that
      supported extrusion bioprinting and the capability to achieve final construct
      shear stiffness values ranging from approximately 100 Pa to 20 kPa. Lastly, we
      integrated these hydrogel bioinks with a 3-D bioprinting platform, and validated
      their use by bioprinting primary liver spheroids in a liver-specific bioink to
      create in vitro liver constructs with high cell viability and measurable
      functional albumin and urea output. This hydrogel bioink system has the potential
      to be a versatile tool for biofabrication of a wide range of tissue construct
      types. STATEMENT OF SIGNIFICANCE: Biochemical and mechanical factors both have
      important implications in guiding the behavior of cells in vivo, yet both realms
      are rarely considered together in the context of biofabrication in vitro tissue
      construct models. We describe a modular hydrogel system that (1) facilitates
      extrusion bioprinting of cell-laden hydrogels, (2) incorporates tissue-specific
      factors derived from decellularized tissue extracellular matrix, thus mimicking
      biochemical tissue profile, and (3) allows control over mechanical properties to
      mimic the tissue stiffness. We believe that employing this technology to attend
      to both the biochemical and mechanical profiles of tissues, will allow us to more
      accurately recapitulate the in vivo environment of tissues while creating
      functional 3-D in vitro tissue constructs that can be used as disease models,
      personalized medicine, and in vitro drug and toxicology screening systems.

PMID- 26210286
TI  - IDH mutation, 1p19q codeletion and ATRX loss in WHO grade II gliomas.
AB  - BACKGROUND: Epigenetic, genetic, and molecular studies have identified several
      diagnostic and prognostic markers in diffuse gliomas. Their importance for
      evaluating WHO grade II gliomas has yet to be specifically delineated. METHODS:
      We analyzed markers, including IDH mutation(IDHmut), 1p19q
      codeletion(1p19qcodel), ATRX expression loss(ATRX loss) and p53 overexpression,
      and outcomes in 159 patients with WHO grade II oligodendroglioma,
      oligoastrocytoma, and astrocytoma (2003-2012). RESULTS: IDHmut was found in
      141(91%) and ATRX loss in 64(87%) of IDHmut-noncodel tumors (p = 0.003). All
      codeleted tumors (n = 66) were IDHmut. Four subgroups were identified: IDHmut
      codel, 66(43%); IDHmut-noncodel-ATRX loss, 60(39%); IDHmut-noncodel-ATRXwt,
      9(6%); IDHwt, 14(9%). Median survival among 4 groups was significantly different
      (p = 0.038), particularly in IDHmut-codel (median survival 15.6 years) compared
      to the remaining 3 groups (p = 0.025). Survival by histology was not significant.
      Overall (OS), but not progression-free (PFS), survival was significantly longer
      with gross total resection vs. biopsy only (p = 0.042). Outcomes for patients
      with subtotal resection were not significantly different from those with biopsy
      only. Among these uniformly treated patients, OS far exceeds PFS, particularly in
      those with 1p/19q codeletion. CONCLUSIONS: For WHO grade II diffuse glioma,
      molecular classification using 1p/19qcodel, IDHmut, and ATRX loss more accurately
      predicts outcome and should be incorporated in the neuropathologic evaluation.

PMID- 26210288
TI  - The Metacognitions about Online Gaming Scale: Development and psychometric
      properties.
AB  - OBJECTIVES: Recent research has suggested that metacognitions may play a role
      across the spectrum of addictive behaviours. The goal of our studies was to
      develop the first self-report scale of metacognitions about online gaming.
      METHOD: We conducted two studies with samples of online gamers (n=225, n=348) to
      test the structure and psychometric properties of the Metacognitions about Online
      Gaming Scale and examined its capacity to predict weekly online gaming hours and
      Internet addiction. RESULTS: Exploratory and confirmatory factor analyses
      supported a three-factor solution: positive metacognitions about online gaming,
      negative metacognitions about the uncontrollability of online gaming, and
      negative metacognitions about the dangers of online gaming. Internal consistency,
      predictive and divergent validity were acceptable. All the factors of the
      Metacognitions about Online Gaming Scale correlated positively with weekly online
      gaming hours and Internet addiction. Regression analyses showed that negative
      metacognitions about the uncontrollability of online gaming and levels of
      Internet addiction were the only significant predictors of weekly online gaming
      hours, and that positive metacognitions about online gaming and negative
      metacognitions about the uncontrollability of online gaming were the only
      significant predictors of Internet addiction. CONCLUSIONS: The Metacognitions
      about Online Gaming Scale was shown to possess good psychometric properties, as
      well as predictive and divergent validity within the populations that were
      tested.

PMID- 26210289
TI  - Complete genome sequence of Rhodococcus erythropolis BG43 (DSM 46869), a degrader
      of Pseudomonas aeruginosa quorum sensing signal molecules.
AB  - Rhodococcus erythropolis BG43 was isolated from soil and characterized as a
      degrader of the quorum sensing signal molecules 2-heptyl-3-hydroxy-4(1H)
      quinolone (the Pseudomonas quinolone signal, PQS) and 2-heptyl-4(1H)-quinolone,
      produced by Pseudomonas aeruginosa. The complete genome of R. erythropolis BG43
      consists of a circular chromosome and three plasmids, one of them circular and
      two linear ones. In total, 6158 protein-coding regions were identified. With this
      genome sequence, the genetic basis of its quorum-quenching ability and possible
      biotechnological applications can be explored further. 

PMID- 26210287
TI  - Post-treatment plasma EBV-DNA positivity predicts early relapse and poor
      prognosis for patients with extranodal NK/T cell lymphoma in the era of
      asparaginase.
AB  - Circulating Epstein-Barr virus (EBV) DNA is a biomarker of EBV-associated
      malignancies. Its prognostic value in early stage NK/T-cell lymphoma (NKTCL) in
      the era of asparaginase was investigated. 68 patients were treated with a median
      of 4 cycles of asparaginase-based chemotherapy followed by a median of 54.6 Gy
      (range 50-60 Gy) radiation. The amount of EBV-DNA was prospectively measured in
      both pretreatment and post-treatment plasma samples by real-time quantitative
      PCR. At the end of treatment, complete response (CR) rate was 79.4%, and overall
      response rate (ORR) was 88.2%. Patients with negative pretreatment EBV-DNA had a
      higher CR rate (96.0% vs. 69.8%, p = 0.023). The 3-year progression-free survival
      (PFS) rate and overall survival (OS) rate was 71% and 83%, respectively. In
      multivariate survival analysis, post-treatment EBV-DNA positivity and treatment
      response (non-CR) were prognostic factors for both worse PFS and OS (p < 0.05).
      Local tumor invasion was also a prognostic factor for worse OS (p = 0.010). In
      patients with CR, post-treatment EBV-DNA positivity correlated with inferior PFS
      and OS (both p < 0.0001). In patients with positive pretreatment EBV-DNA,
      negative post-treatment EBV-DNA correlated with better PFS and OS (both p <
      0.0001). These findings indicate that post-treatment EBV-DNA positivity can
      predict early relapse and poor prognosis for patients with early stage NKTCL in
      the era of asparaginase, and may be used as an indicator of minimal residual
      disease.

PMID- 26210290
TI  - Complete genome sequence of novel carbon monoxide oxidizing bacteria Citrobacter
      amalonaticus Y19, assembled de novo.
AB  - We report here the complete genome sequence of Citrobacter amalonaticus Y19
      isolated from an anaerobic digester. PacBio single-molecule real-time (SMRT)
      sequencing was employed, resulting in a single scaffold of 5.58Mb. The sequence
      of a mega plasmid of 291Kb size is also presented. 

PMID- 26210291
TI  - Complete genome sequence of a malodorant-producing acetogen, Clostridium
      scatologenes ATCC 25775(T).
AB  - Clostridium scatologenes ATCC 25775(T) is an acetogenic anaerobic bacteria known
      to be capable of synthesizing volatile fatty acids and solvents from CO2 or CO on
      its autotrophic mode and producing 3-methylindole and 4-methylphenol on its
      heterotrophic mode. Here, we report the complete genome sequence of this strain,
      which might provide a lot of valuable information for developing metabolic
      engineering strategies to produce biofuels or chemicals from greenhouse gases. 

PMID- 26210292
TI  - A new reusable suturing device for vaginal sacrospinous fixation: feasibility and
      safety study.
AB  - OBJECTIVE: We sought to evaluate the feasibility and safety of SeraPro((r))
      (Serag-Wiessner, Germany), an innovative reusable suturing device for vaginal
      sacrospinous ligament fixation. STUDY DESIGN: We reviewed the electronic files of
      all women who underwent vaginal sacrospinous ligament fixation with SeraPro((r))
      for apical pelvic floor prolapse, with or without mesh implant, performed between
      April 2013 and September 2013. Preoperative demographic, clinical, operative and
      postoperative data were analyzed. The women were interviewed and examined before
      the procedure, at one month postoperatively and tele-interviewed again after
      three months. RESULTS: Overall, 88 women were included in the study. Fifty-three
      patients (60.2%) had additional anterior mesh placement, 42 (47.7%) had posterior
      mesh, and 16 (18.2%) had both anterior and posterior mesh insertion. Five
      patients (5.7%) had no mesh implant. Sixteen patients (18.2%) had an additional
      mid-urethral sling for the treatment of stress urinary incontinence. No
      significant technical difficulty was recorded at the procedures. None of the
      patients had significant long-term morbidity. The mean 3-month follow-up
      demonstrated significant anatomical and functional improvement. CONCLUSIONS: The
      SeraPro((r)) reusable suturing device is a feasible and safe tool for
      sacrospinous ligament fixation during vaginal pelvic floor reconstruction.

PMID- 26210293
TI  - Barriers to Long-Acting Reversible Contraceptive Uptake Among Homeless Young
      Women.
AB  - STUDY OBJECTIVE: To identify barriers to long-acting reversible contraception
      (LARC) uptake among homeless young women. DESIGN: In this mixed methods study
      surveys and guided interviews were used to explore women's contraceptive and
      reproductive experiences, interactions with the health care system, and their
      histories of homelessness. SETTING: All surveys and interviews were conducted at
      a homeless drop-in center or shelter. PARTICIPANTS: Fifteen women between 18 and
      24 years of age with a past year history of homelessness. INTERVENTIONS: None.
      MAIN OUTCOME MEASURES: Perceived barriers to contraceptive use, including
      knowledge and access barriers and interactions with the health care system around
      reproductive health. RESULTS: Confusion about the possibility of early
      termination of LARC, and the perception that providers deliberately withhold
      selective information about contraceptive options to bias contraceptive decision
      making, were 2 key new findings. Women also reported interest in visual aids
      accompanying verbal contraceptive counseling. Pregnancy attitudes and history of
      reproductive and sexual coercion also influenced contraceptive decision-making
      and reported interest in LARC methods. CONCLUSION: Comprehensive counseling about
      all contraceptive options, including LARC, are important for targeting the
      perceived gaps in contraceptive education and care among homeless young women.

PMID- 26210294
TI  - Prevalence and diversity of enterotoxin genes with genetic background of
      Staphylococcus aureus isolates from different origins in China.
AB  - Staphylococcal enterotoxins (SE) induce toxin-mediated diseases, such as food
      poisoning. In the present study, 568 isolates from different sources were tested
      for the prevalence of 18 SE genes and performed spa typing. In addition, we
      characterized the relationships between the distribution of SE genes and
      molecular clones based on multilocus sequence typing (MLST), spa and
      staphylococcal cassette chromosome mec (SCCmec) typing in selected 250 isolates.
      Approximately 54.40% of the isolates from different sources harbored one or more
      SE genes forming 120 distinct gene profiles. Seven genes, sea, seb, seg, seo,
      sem, seq, and sel were more frequently detected. The distributions of the SE
      genes among the isolates from human, animals, and foodborne origins were highly
      different with isolates from environments (P<0.01). The classic SE genes in both
      foodborne and human origin isolates were significantly higher than that in animal
      origin isolates (P<0.01), whereas the prevalence of genes of egc cluster and the
      other genes was similar in human, animal, and foodborne origin isolates (P>0.05).
      We identified two important gene clusters, sea-sek-seq, which is closely related
      to hospital-acquired (HA) methicillin-resistant Staphylococcus aureus (MRSA)-III,
      and the egc cluster, which accounts for nearly half of all genes. Approximately
      71% isolates could be typed by spa, yielding 103 spa types, of which 18 spa types
      were primary types. In clonal complex (CC) 239, an important Asian HA-MRSA-III
      clone from humans, nearly all isolates harbored complete or partial sea-sek-seq
      cluster; the main spa types were t030 and t037. In CC630, an important new
      community-associated (CA) MRSA-V CC in China, only sporadic SE genes, three main
      spa types, t4549, t2196, and t377 were observed. The egc cluster coexisting with
      other genes was present in isolates of CC5, CC9, CC1281, CC1301, CC30 and
      sequence type (ST) 25, but completely absent in isolates of CC239, CC59, CC7, and
      CC88. The results illustrate the genetic clonal diversity and the identity of S.
      aureus isolates from different sources with respect to SE genes and highlight a
      correlation between SE genes or gene clusters and CCs, spa, and MRSA clones. The
      foodborne and human origin isolates were the main potential causes of classic
      staphylococcal foodborne poisonings, whereas isolates harboring novel genes were
      new potential hazards to food safety. 

PMID- 26210295
TI  - The motivation and actions of Australians concerning brain health and dementia
      risk reduction.
AB  - ISSUE ADDRESSED: Alzheimer's disease and dementia are recognised as critical
      public health priorities. This study investigated intentions and behaviours
      concerning brain health and dementia risk reduction among Australians. METHODS: A
      cross-sectional survey of 1000 persons aged 20-75 years measured knowledge,
      beliefs, intentions and behaviours concerning brain health and dementia. The
      demographic, experiential and cognitive factors associated with intentions and
      actions were examined. RESULTS: Around half of respondents were motivated to
      improve brain health. Behaviours most often reported were mental activity (19%),
      physical activity (9.6%) and dietary action (6.5%). Actions were most likely
      among women (OR 1.59, 95% CI 1.19-2.14), those aged 60 years and over (OR 3.07,
      95% CI 2.01-2.58), with university education (OR 1.67, 95% CI 1.08-2.58) or with
      prior contact with a person with dementia (OR 1.99, 95% CI 1.12-3.56). Both
      intentions and actions were associated with moderate to high knowledge, and
      beliefs and confidence that favoured dementia risk reduction. CONCLUSIONS: A
      lower proportion of Australians reported taking action to improve brain health
      than who expressed intentions in this regard. Strategies are needed to improve
      knowledge about the range of behaviours that contribute to dementia risk
      reduction and to increase confidence that this outcome is personally achievable.
      SO WHAT? The burden of disease due to Alzheimer's disease and dementia is growing
      dramatically. It is essential to promote awareness that dementia is not an
      inevitable result of ageing and to increase understanding that action can be
      taken throughout the life course to promote brain health.

PMID- 26210296
TI  - Erratum to: Nonuse of dental service by schoolchildren in Southern Brazil: impact
      of socioeconomics, behavioral and clinical factors.

PMID- 26210297
TI  - Mobilization of arsenic, lead, and mercury under conditions of sea water
      intrusion and road deicing salt application.
AB  - Water geochemistry data from complexly designed salt-solution injection
      experiments in the laboratory, coastal aquifers of Bangladesh and Italy, taken
      from the literature, and two salted watersheds of New Jersey, US were collected
      and analyzed to study the geochemical mechanisms that mobilize As, Pb, and Hg
      under varied salting conditions. Overall, increased NaCl-concentrations in
      aquifers and soil are found to increase the release of Pb and Hg into the water.
      Reducing environments and possible soil dispersion by hydrated Na(+) are found to
      lead to an increase of As-concentration in water. However, the application of a
      pure NaCl salt solution in the column injection experiment was found to release
      less As, Pb, and Hg initially from the soil and delay their concentration
      increase, when compared to the application of CaCl2 and NaCl mixed salts (at 6:4
      weight ratio). The concentration correlation dendrogram statistical analyses of
      the experimental and field data suggest that the release of As, Hg, and Pb into
      groundwater and the soil solution depends not only on the salt level and content,
      but also on the redox condition, dissolved organic matter contents,
      competitiveness of other ions for exchange sites, and source minerals. With the
      ongoing over-exploration of coastal aquifers from increased pumping, continued
      sea-level rise, and increased winter deicing salt applications in salted
      watersheds of many inland regions, the results of this study will help understand
      the complex relation between the concentrations of As, Pb, and Hg and increased
      salt level in a coastal aquifer and in soils of a salted watershed. 

PMID- 26210299
TI  - Phospholipid-driven differences determine the action of the synthetic
      antimicrobial peptide OP-145 on Gram-positive bacterial and mammalian membrane
      model systems.
AB  - OP-145, a synthetic antimicrobial peptide developed from a screen of the human
      cathelicidin LL-37, displays strong antibacterial activities and is--at
      considerably higher concentrations--lytic to human cells. To obtain more insight
      into its actions, we investigated the interactions between OP-145 and liposomes
      composed of phosphatidylglycerol (PG) and phosphatidylcholine (PC), resembling
      bacterial and mammalian membranes, respectively. Circular dichroism analyses of
      OP-145 demonstrated a predominant alpha-helical conformation in the presence of
      both membrane mimics, indicating that the different membrane-perturbation
      mechanisms are not due to different secondary structures. Membrane thinning and
      formation of quasi-interdigitated lipid-peptide structures was observed in PG
      bilayers, while OP-145 led to disintegration of PC liposomes into disk-like
      micelles and bilayer sheets. Although OP-145 was capable of binding lipoteichoic
      acid and peptidoglycan, the presence of these bacterial cell wall components did
      not retain OP-145 and hence did not interfere with the activity of the peptide
      toward PG membranes. Furthermore, physiological Ca++ concentrations did neither
      influence the membrane activity of OP-145 in model systems nor the killing of
      Staphylococcus aureus. However, addition of OP-145 at physiological Ca++
      concentrations to PG membranes, but not PC membranes, resulted in the formation
      of elongated enrolled structures similar to cochleate-like structures. In
      summary, phospholipid-driven differences in incorporation of OP-145 into the
      lipid bilayers govern the membrane activity of the peptide on bacterial and
      mammalian membrane mimics.

PMID- 26210298
TI  - The crucial role of vitamin C and its transporter (SVCT2) in bone marrow stromal
      cell autophagy and apoptosis.
AB  - Vitamin C is an antioxidant that plays a vital role in various biological
      processes including bone formation. Previously, we reported that vitamin C is
      transported into bone marrow stromal cells (BMSCs) through the sodium dependent
      Vitamin C Transporter 2 (SVCT2) and this transporter plays an important role in
      osteogenic differentiation. Furthermore, this transporter is regulated by
      oxidative stress. To date, however, the exact role of vitamin C and its
      transporter (SVCT2) in ROS regulated autophagy and apoptosis in BMSCs is poorly
      understood. In the present study, we observed that oxidative stress decreased
      survival of BMSCs in a dose-dependent manner and induced growth arrest in the G1
      phase of the cell cycle. These effects were accompanied by the induction of
      autophagy, confirmed by P62 and LC3B protein level and punctate GFP-LC3B
      distribution. The supplementation of vitamin C significantly rescued the BMSCs
      from oxidative stress by regulating autophagy. Knockdown of the SVCT2 transporter
      in BMSCs synergistically decreased cell survival even under low oxidative stress
      conditions. Also, supplementing vitamin C failed to rescue cells from stress. Our
      results reveal that the SVCT2 transporter plays a vital role in the mechanism of
      BMSC survival under stress conditions. Altogether, this study has given new
      insight into the role of the SVCT2 transporter in oxidative stress related
      autophagy and apoptosis in BMSCs. 

PMID- 26210300
TI  - Imaging potassium-flux through individual electropores in droplet interface
      bilayers.
AB  - Using total internal reflection fluorescence microscopy of droplet interface
      bilayers containing the potassium-sensitive fluorophore APG-4, we imaged the
      ionic flux through individual electropores. We are able to monitor up to 30
      individual pores in parallel and show voltage dependent responses in fluorescence
      that corresponds to the measured ionic current. These experiments help quantify
      the scope and current limitations of optical single channel recordings of
      potassium flux. This article is part of a Special Issue entitled: Pore-Forming
      Toxins edited by Mauro Dalla Serra and Franco Gambale. 

PMID- 26210302
TI  - A new detection method for a newly revealed mechanism of pyrethroid resistance
      development in Varroa destructor.
AB  - The Varroa destructor mite has recently displayed an ever increasing resistance
      to new drugs, contributing to CCD proliferation. This work was aimed at
      determining new viable methods for identifying the pyrethroid resistance of V.
      destructor and DNA methylation in resistant and sensitive mites. DNA was
      extracted from Varroa mites. Nucleotide changes in the DNA of pyrethroid
      resistant, pyrethroid-sensitive, and control mites were identified with
      polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in
      the case of five mitochondrial gene fragments. More bands were observed in the
      drug-resistant mites than in the other two groups. Sequencing confirmed these
      observations. Decreased global DNA methylation levels were observed in the
      pyrethroid-resistant mites. There exists a previously undescribed mechanism of
      pyrethroid resistance development in Varroa mites. The PCR-SSCP methods can be
      considered and further developed as useful tools for detecting V. destructor
      resistance. 

PMID- 26210301
TI  - Host-pathogen interactions in malaria: cross-kingdom signaling and mitochondrial
      regulation.
AB  - Malaria parasite-host interactions are complex and have confounded available
      drugs and the development of vaccines. Further, we now appreciate that
      interventions for malaria elimination and eradication must include therapeutics
      with intrinsic transmission blocking activity to treat the patient and prevent
      disease spread. Studies over the past 15 years have revealed significant
      conservation in the response to infection in mosquito and human hosts. More
      recently, we have recognized that conserved cell signaling cascades in mosquitoes
      and humans dictate infection outcome through the regulation of mitochondrial
      function and biogenesis, which feed back to host immunity, basic intermediary
      metabolism, and stress responses. These responses - reflected clearly in the
      primeval insect host - provide fertile ground for innovative strategies for both
      treatment and transmission blocking. 

PMID- 26210303
TI  - Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of
      schizophrenia: a bicentric randomized controlled pilot study.
AB  - Despite many pharmacological and psychosocial treatment options, schizophrenia
      remains a debilitating disorder. Thus, new treatment strategies rooted in the
      pathophysiology of the disorder are needed. Recently, vagus nerve stimulation
      (VNS) has been proposed as a potential treatment option for various
      neuropsychiatric disorders including schizophrenia. The objective of this study
      was to investigate for the first time the feasibility, safety and efficacy of
      transcutaneous VNS in stable schizophrenia. A bicentric randomized, sham
      controlled, double-blind trial was conducted from 2010 to 2012. Twenty
      schizophrenia patients were randomly assigned to one of two treatment groups. The
      first group (active tVNS) received daily active stimulation of the left auricle
      for 26 weeks. The second group (sham tVNS) received daily sham stimulation for 12
      weeks followed by 14 weeks of active stimulation. Primary outcome was defined as
      change in the Positive and Negative Symptom Scale total score between baseline
      and week 12. Various other secondary measures were assessed to investigate safety
      and efficacy. The intervention was well tolerated with no relevant adverse
      effects. We could not observe a statistically significant difference in the
      improvement of schizophrenia psychopathology during the observation period.
      Neither psychopathological and neurocognitive measures nor safety measures showed
      significant differences between study groups. Application of tVNS was well
      tolerated, but did not improve schizophrenia symptoms in our 26-week trial. While
      unsatisfactory compliance questions the feasibility of patient-controlled
      neurostimulation in schizophrenia, the overall pattern of symptom change might
      warrant further investigations in this population.

PMID- 26210304
TI  - Clinical trial analyzing the impact of continuous defocused CO2 laser
      vaporisation on the malignant transformation of erosive oral lichen planus.
AB  - The erosive oral lichen planus (OLP) represents a management challenge to the
      clinician and can have debilitating consequences to patients' quality of life.
      The aims of this work were to determine the incidence of malignant transformation
      to squamous cell carcinoma (SCC) in patients undergoing traditional symptomatic
      treatments (oral salve containing lidocaine hydrochloride or systemic diclofenac)
      compared to patients that were managed with a defocused continuous CO2 laser
      beam. A total of 171 patients with histologically confirmed erosive OLP were
      included into this study. After treatment, patients were assessed until
      completion of wound healing, at least every 3-6 months for the first 2 years, and
      every 6-12 months thereafter. The study included 87 women (50.9%) and 84 men
      (49.1%). A total of 103 patients (60.2%) underwent symptomatic conservative
      treatment, and 68 patients (39.8%) underwent continuous defocused CO2 laser
      treatments. SCC developed in 16 patients (9.4%), 2 patients (2.9%) after
      continuous defocused CO2 laser treatment and 14 patients (13.6%) with symptomatic
      treatment only. This study provides insight into the potential impact of the CO2
      laser in the management of patients with erosive OLP and the influence on the
      recurrence rate of erosive OLP, as well as malignant transformation to oral SCC. 

PMID- 26210305
TI  - Surgical care burden in orbito-temporal neurofibromatosis: Multiple procedures
      and surgical care duration analysis in 47 consecutive adult patients.
AB  - Patients with orbito-temporal neurofibromatosis (OTNF) bear a heavy burden of
      surgical care. We studied 47 consecutive patients with OTNF from the French
      Neurofibromatosis 1 Referral Center cohort (n > 900), over a 15-year period to
      determine the clinical features most likely to predict repeat surgery and longer
      duration of surgical care. Forty-seven patients (5.2% of the NF1 patients'
      cohort) underwent 79 procedures with a 4.8 years average follow-up. Soft-tissue
      surgery had a high revision rate (19/45 patients), skeletal surgery did not (2/13
      patients). Transosseous wire canthopexy and facial aesthetic unit remodeling were
      associated with stable outcome. Ptosis repair carried an unfavorable outcome,
      particularly in the presence of sphenoid dysplasia. Stable skeletal remodeling
      was achieved with polyethylene implants and/or cementoplasty. Multiple procedures
      were undertaken in 70% of patients and were predicted by the NF volume,
      canthopexy, skeletal dysplasia, or a Jackson's classification 2 and/or 3; but not
      by declining visual acuity. A classification based upon predictive risk of
      repeated procedures is proposed: Group 1: Isolated soft tissue infiltration not
      requiring levator palpebrae or canthal surgery; Group 2: Soft tissue involvement
      requiring ptosis repair or canthopexy, or NF great axis over 4.5 cm; Group 3:
      Presence of sphenoid dysplasia with pulsatile proptosis, regardless of visual
      acuity.

PMID- 26210306
TI  - An unusual bowel complication during molecularly-targeted therapy.

PMID- 26210307
TI  - An unusual retroperitoneal tumour mimicking adrenal pheochromocytoma.

PMID- 26210308
TI  - Interest of intra-operative 3D imaging in spine surgery: a prospective randomized
      study.
AB  - PURPOSE: We report a single-center, prospective, randomized study for pedicle
      screw insertion in opened and percutaneous spine surgeries, using a computer
      assisted surgery (CAS) technique with three-dimensional (3D) intra-operative
      images intensifier (without planification on pre-operative CT scan) vs
      conventional surgical procedure. MATERIAL AND METHOD: We included 143 patients:
      Group C (conventional, 72 patients) and Group N (3D Fluoronavigation, 71
      patients). We measured the pedicle screw running time, and surgeon's radiation
      exposure. All pedicle runs were assessed according to Heary by two independent
      radiologists on a post-operative CT scan. RESULTS: 3D Fluoronavigation appeared
      less accurate in percutaneous procedures (24 % of misplaced pedicle screws vs 5 %
      in Group C) (p = 0.007), but more accurate in opened surgeries (5 % of misplaced
      pedicle screws vs 17 % in Group C) (p = 0.025). For one vertebra, the average
      surgical running time reached 8 min in Group C vs 21 min in Group N for
      percutaneous surgeries (p = 3.42 * 10(-9)), 7.33 min in Group C vs 16.33 min in
      Group N (p = 2.88 * 10(-7)) for opened surgeries. The 3D navigation device
      delivered less radiation in percutaneous procedures [0.6 vs 1.62 mSv in Group C
      (p = 2.45 * 10(-9))]. For opened surgeries, it was twice higher in Group N with
      0.21 vs 0.1 mSv in Group C (p = 0.022). CONCLUSION: The rate of misplaced pedicle
      screws with conventional techniques was nearly the same as most papers and a
      little bit higher with CAS. Surgical running time and radiation exposure were
      consistent with many studies. Our work hypothesis is partially confirmed,
      depending on the type of surgery (opened or closed procedure).

PMID- 26210309
TI  - Surgery or physical activity in the management of sciatica: a systematic review
      and meta-analysis.
AB  - PURPOSE: Previous reviews have compared surgical to non-surgical management of
      sciatica, but have overlooked the specific comparison between surgery and
      physical activity-based interventions. METHODS: Systematic review using MEDLINE,
      CINAHL, Embase and PEDro databases was conducted. Randomised controlled trials
      comparing surgery to physical activity, where patients were experiencing the
      three most common causes of sciatica-disc herniation, spondylolisthesis and
      spinal stenosis. Two independent reviewers extracted pain and disability data
      (converted to a common 0-100 scale) and assessed methodological quality using the
      PEDro scale. The size of the effects was estimated for each outcome at three
      different time points, with a random effects model adopted and the GRADE approach
      used in summary conclusions. RESULTS: Twelve trials were included. In the short
      term, surgery provided better outcomes than physical activity for disc
      herniation: disability [WMD -9.00 (95 % CI -13.73, -4.27)], leg pain [WMD -16.01
      (95 % CI -23.00, -9.02)] and back pain [WMD -12.44 (95 % CI -17.76, -7.09)]; for
      spondylolisthesis: disability [WMD -14.60 (95 % CI -17.12, -12.08)], leg pain
      [WMD -35.00 (95 % CI -39.66, -30.34)] and back pain [WMD -20.00 (95 % CI -24.66, 
      15.34)] and spinal stenosis: disability [WMD -11.39 (95 % CI -17.31, -5.46)], leg
      pain [WMD, -27.17 (95 % CI -35.87, -18.46)] and back pain [WMD -20.80 (95 % CI 
      25.15, -16.44)]. Long-term and greater than 2-year post-randomisation results
      favoured surgery for spondylolisthesis and stenosis, although the size of the
      effects reduced with time. For disc herniation, no significant effect was shown
      for leg and back pain comparing surgery to physical activity. CONCLUSION: There
      are indications that surgery is superior to physical activity-based interventions
      in reducing pain and disability for disc herniation at short-term follow-up only;
      but high-quality evidence in this field is lacking (GRADE). For spondylolisthesis
      and spinal stenosis, surgery is superior to physical activity up to greater than
      2 years follow-up. Results should guide clinicians and patients when facing the
      difficult decision of having surgery or engaging in active care interventions.
      PROSPERO registration number : CRD42013005746.

PMID- 26210310
TI  - Percutaneous pars interarticularis screw fixation: a technical note.
AB  - PURPOSE: A conventional midline posterior approach is used for most of the
      described surgical techniques. We describe a technique of percutaneous fixation
      of the pars interarticularis, augmented where necessary by grafting the defect,
      which minimises muscle injury. METHOD: A 4.5 mm partially threaded dynamic
      compression screw is placed over a wire inserted percutaneously across the pars
      interarticularis defect. Compression is achieved across the pars interarticularis
      defect on placement of the screw. The screw is locked in a compressed state.
      RESULTS: The patient is mobilised the same day with a corset for comfort and
      discharged the following day. Aerobic fitness is maintained for 3 months; then,
      focused rehabilitation performed until a CT scan confirms healing at 5-6 months,
      at which stage full (sports) activity is resumed. CONCLUSIONS: The minimal tissue
      injury and small incision used allow for the minimising of complications and for
      a rapid recovery and discharge from hospital. With adolescents, we have the
      opportunity to treat symptomatic pars interarticularis defects with minimal
      disruption to their academic and physical development.

PMID- 26210311
TI  - Combined endoscopic transnasal and transoral approach for extensive upper
      cervical osteoradionecrosis.
AB  - PURPOSE: Osteoradionecrosis (ORN) is a rare yet well-recognized complication
      following radiotherapy to the head and neck. We illustrate the only case of a
      spontaneous extrusion of the sequestered C1 arch through the oral cavity and
      discuss our experience with a combined endoscopic transnasal and transoral
      approach for cervical ORN. METHODS: A 56-year-old female presented with a 3-month
      history of blood-stained nasal discharge. She had been treated with radiotherapy
      for nasopharyngeal carcinoma 25 years earlier. Flexible nasal endoscopy
      demonstrated an exposed bone with an edematous posterior nasopharyngeal mass.
      Computed tomography showed a pre-vertebral mass with destruction of C1 and C2.
      She underwent occipito-cervical fusion followed by a combined transnasal and
      transoral endoscopic debridement of non-viable bone in the same perioperative
      setting. Healing of the raw mucosa was by secondary intention and reconstruction
      was not performed. RESULTS: Histopathological examination reported ulcerated
      inflamed granulation tissue with no evidence of malignancy. During follow-up, she
      remained neurologically intact with no recurrence. CONCLUSION: Using both nasal
      and oral spaces allows placement of the endoscope in the nasal cavity and
      surgical instruments in the oral cavity without splitting the palate. Hence, the
      endoscopic transnasal and transoral approach has vast potential to be effective
      in carefully selected cases of cervical ORN.

PMID- 26210312
TI  - WHO tobacco report focuses on increased taxation.

PMID- 26210313
TI  - Rethinking COPD diagnosis: imaging and GOLD criteria.

PMID- 26210314
TI  - Extended warfarin treatment after pulmonary embolism.

PMID- 26210315
TI  - Postpartum uterine diseases and their impacts on conception and days open in
      dairy herds in Italy.
AB  - The objective of this study was to describe the incidence and the impact of
      postpartum uterine diseases in postpartum cows on future uterine status and
      reproductive performance in large Italian dairy herds. This study provides an
      important quantitative estimate of uterine and postpartum diseases incidence that
      afflict high-producing Italian dairy cows. The total number of cows included in
      the study was 1498 on three farms; all cows were followed from the dry period
      until 300 days postpartum. All farms used high-quality data collection systems
      and standard operating procedures: weekly herd health visits, monthly Dairy Herd
      Improvement Association visits, and, due to cheese-making milk quality
      requirements, a supplementary milk sample collected at 7 +/- 3 days postpartum
      evaluated for milk components. Clinical metritis in primiparous cows did not
      change the time to the first artificial insemination (AI) or days open;
      conversely, clinical metritis in multiparous cows had impact on the time to first
      AI (hazard ratio: 0.66, P < 0.01) and resulted in a lower conception rate at
      first insemination and a increase in days open (odds ratio: 0.64, P < 0.05).
      Clinical endometritis had a strong deleterious effect on first AI conception rate
      (odds ratio: 0.34, P < 0.05) and days open across all lactations (hazard ratio:
      0.68, P < 0.05). Persistent metritis, defined as the presence of both clinical
      metritis and clinical endometritis in the same animal in the same lactation,
      caused low conception rate both in the first-lactation and in older cows and had
      a strong negative effect on the proportion of pregnant cows at 300 days (P <
      0.05). In conclusion, the impact of endometritis on fertility was true across
      lactation groups. A good management and precocious diagnosis of the pathologies
      is not resolutive to restore good fertility parameters, and understanding the
      immune response in first-lactation cows may be of value for developing
      alternative intervention protocols for older-lactation cows.

PMID- 26210316
TI  - Extractions of steady-state auditory evoked fields in normal subjects and
      tinnitus patients using complementary ensemble empirical mode decomposition.
AB  - BACKGROUND: Auditory steady-state response (ASSR) induced by repetitive auditory
      stimulus is commonly used for audiometric testing. ASSR can be measured using
      electro-encephalography (EEG) and magnetoencephalography (MEG), referred to as
      steady-state auditory evoked potential (SSAEP) and steady-state auditory evoked
      field (SSAEF), respectively. However, the signal level of SSAEP and SSAEF are
      weak so that signal processing technique is required to increase its signal-to
      noise ratio. In this study, a complementary ensemble empirical mode decomposition
      (CEEMD)-based approach is proposed in MEG study and the extraction of SSAEF has
      been demonstrated in normal subjects and tinnitus patients. METHODS: The CEEMD
      utilizes noise assisted data analysis (NADA) approach by adding positive and
      negative noise to decompose MEG signals into complementary intrinsic mode
      functions (IMF). Ten subjects (five normal and five tinnitus patients) were
      studied. The auditory stimulus was designed as 1 kHz carrier frequency with 37 Hz
      modulation frequency. Two channels in the vicinities of right and left temporal
      areas were chosen as channel-of-interests (COI) and decomposed into IMFs. The
      spatial distribution of each IMF was correlated with a pair of left- and right
      hemisphere spatial templates, designed from each subject's N100m responses in
      pure-tone auditory stimulation. IMFs with spatial distributions highly correlated
      with spatial templates were identified using K-means and those SSAEF-related IMFs
      were used to reconstruct noise-suppressed SSAEFs. RESULTS: The current strengths
      estimated from CEEMD processed SSAEF showed neural activities greater or
      comparable to those processed by conventional filtering method. Both the normal
      and tinnitus groups showed the phenomenon of right-hemisphere dominance. The mean
      current strengths of auditory-induced neural activities in tinnitus group were
      larger than the normal group. CONCLUSIONS: The present study proposes an
      effective method for SSAEF extraction. The enhanced SSAEF in tinnitus group
      echoes the decreased inhibition in tinnitus's central auditory structures as
      reported in previous studies.

PMID- 26210317
TI  - The antidepressant-like activity of 6-methoxy-2-[4-(2-methoxyphenyl)piperazin-1
      yl]-9H-xanthen-9-one involves serotonergic 5-HT(1A) and 5-HT(2A/C) receptors
      activation.
AB  - Xanthone derivatives have been shown to posses many biological properties. Some
      of them act within the central nervous system and show neuroprotective or
      antidepressant-like properties. Taking this into account we investigated
      antidepressant-like activity in mice and the possible mechanism of action of 6
      methoxy-2-[4-(2-methoxyphenyl)piperazin-1-yl]-9H-xanthen-9-one (HBK-11) - a new
      xanthone derivative. We demonstrated that HBK-11 produced antidepressant-like
      effects in the forced swim test and tail suspension test, comparable to that of
      venlafaxine. The combined treatment with sub-effective doses of HBK-11 and
      fluoxetine (but not reboxetine or bupropion) significantly reduced the immobility
      in the forced swim test. Moreover, the antidepressant-like activity of HBK-11 in
      the aforementioned test was blocked by p-chlorophenylalanine, and significantly
      reduced by serotonergic 5HT1A receptor antagonist - WAY-1006335 and 5HT2A/C
      receptor antagonist - ritanserin. As none of the above treatments influenced the
      spontaneous locomotor activity, it can be concluded that HBK-11 mediates its
      activity through a serotonergic system, and its antidepressant-like effect
      involves 5HT1A and 5HT2A/C receptor activation. Furthermore, at antidepressant
      like doses HBK-11 did not cause the mice to display locomotor deficits in rotarod
      or chimney tests. Considering the pharmacokinetic profile, HBK-11 demonstrated
      rapid absorption after i.p. administration, high clearance value, short terminal
      half-life, very high volume of distribution and incomplete bioavailability. The
      compound studied had good penetration into the brain tissue of mice. Since
      studied xanthone derivative seems to present interesting, untypical mechanism of
      antidepressant-like action i.e. 5HT2A/C receptor activation, it may have a
      potential in the treatment of depressive disorders, and surely requires further
      studies. 

PMID- 26210318
TI  - Case report of nipple shield trauma associated with breastfeeding an infant with
      high intra-oral vacuum.
AB  - BACKGROUND: Nipple pain is associated with early cessation of breastfeeding and
      may be caused by high intra-oral vacuum. However identification of high intra
      oral vacuum is typically restricted to the research setting. This is the first
      reported case of an infant with high intra-oral vacuum that was clinically
      identified through a specific pattern of nipple trauma associated with nipple
      shield use. Knowledge of clinical signs associated with high intra-oral vacuum
      may facilitate early recognition of this unusual breastfeeding challenge. CASE
      PRESENTATION: The mother of an exclusively breastfed 3 month old infant had
      severe bilateral nipple pain with minimal trauma that persisted from birth. The
      nipples were not misshapen immediately after breastfeeding and adjustments to
      infant attachment at the breast did not attenuate the pain. Examination of the
      infant's oral anatomy was unremarkable with no ankyloglossia present.
      Microbiological cultures of nipple swabs and breast milk were negative for
      bacterial and fungal growth, and prescribed antimicrobial treatments did not
      reduce the nipple pain. Mild blanching and erythema of the nipples were
      occasionally observed, and were not consistent with nipple vasospasm. Nipple
      shields were used regularly as they modified the pain, although this resulted in
      blisters that corresponded with the nipple shield holes. Measurement of infant
      intra-oral vacuum during breastfeeding confirmed intra-oral vacuum up to 307 %
      higher than reference values. Breastfeeding gradually became less painful, and
      after 6 months was completely comfortable. CONCLUSIONS: High intra-oral vacuum is
      difficult to assess in the clinical setting and is likely an under-reported cause
      of early weaning that is not well understood. This original case report
      highlights high intra-oral vacuum as at differential diagnosis to be considered
      by health professionals when evaluating mothers experiencing strong nipple pain
      during the initiation of breastfeeding. A clinical screening tool is needed to
      enable prompt identification of these infants.

PMID- 26210319
TI  - Photosynthetic characteristics, antioxidant capacity and biomass yield of wheat
      exposed to intermittent light irradiation with millisecond-scale periods.
AB  - Energy consumption and output are two very important standards for evaluating the
      reliability of electric light sources when plants are grown in a controlled
      environment. As a primary source of energy, light is one of the most important
      environmental factors for wheat growth. The objective of this study was to
      investigate the influences of light/dark cycle operation with millisecond-scale
      period on the growth of wheat, photosynthetic characteristics, antioxidant
      capacity and biomass yield and quality during their life cycle. Four types of
      intermittent lighting with the same intensity were employed: a light/dark
      (0.5/0.5 ms) light (50%), a light/dark (0.7/0.3 ms) light (70%), a light/dark
      (0.8/0.2 ms) light (80%) and a continuous light (100%). The results showed that
      the wheat cultivated in the 80% light was characterized by highest photosynthetic
      rate and lowest lignin in inedible biomass, which was more beneficial to recycle
      substances in the processes of the environment regeneration. The data were
      comparable to those under continuous light condition in terms of chlorophyll
      concentration, antioxidant capacity, harvest index (HI) and thousand kernel
      weight (TKW). Wheat was sensitive to intermittent illumination which
      significantly affected those indices of growth and physiology, especially at
      heading and flowering stages.

PMID- 26210320
TI  - The acquisition of desiccation tolerance in developing Vicia hirsuta seeds
      coincides with an increase in galactinol synthase expression and soluble alpha-D
      galactosides accumulation.
AB  - Galactinol is the galactosyl donor for the biosynthesis of both the raffinose
      family oligosaccharides (RFOs) and galactosyl cyclitols (Gal-C). Its synthesis by
      galactinol synthase (GolS, EC 2.4.1.123) is the first committed step of the
      soluble alpha-D-galactosides biosynthetic pathway in orthodox seeds. The
      deposition of galactosides in seeds is suggested to be associated with
      desiccation tolerance (DT). In this work, for the first time, we cloned and
      characterized two Vicia hirsuta (L.) S.F. Gray galactinol synthase genes
      (VhGolS1, VhGolS2), analyzed galactinol synthase activity and measured the
      accumulation of galactosides of both sucrose and D-pinitol in relation to the
      acquisition of DT in developing seeds of this wild species. A developmentally
      induced increase of VhGolS1 expression preceded the rise of GolS activity in
      crude protein extract from maturing seeds, while the expression of the VhGolS2
      gene remained low. GolS activity peaked just after the beginning of the
      maturation drying phase. The increase of GolS activity was not followed by
      galactinol accumulation, instead the high enzyme activity was related to high
      levels of galactose bound in soluble galactosides of the RFO and galactosyl
      pinitol series. Acquisition of DT coincided with an increase of VhGolS1
      expression, high galactinol synthase activity and the accumulation of
      oligogalactosides in seeds. DT was positively correlated with the high content of
      soluble alpha-D-galactosides of both the RFO and galactosyl pinitol series as
      well as with the amount of galactose bound in these galactosides.

PMID- 26210321
TI  - The crystal structure of heme acquisition system A from Yersinia
      pseudotuberculosis (HasAypt): Roles of the axial ligand Tyr75 and two distal
      arginines in heme binding.
AB  - Some Gram-negative pathogens utilize an extracellular heme-binding protein called
      hemophore to satisfy their needs for iron, a metal element essential for most
      living things. We report here crystal structures of heme acquisition system A
      from Yersinia pseudotuberculosis (HasAypt) and its Y75A mutant. The wild-type
      HasAypt structure revealed that the heme iron is coordinated with Tyr75 and a
      water molecule. The heme-bound water molecule makes extensive hydrogen bond
      network that includes Arg40 and Arg144 on the distal heme pocket. Arg40, highly
      conserved for HasAs from Yersinia species, forms a salt bridge with the
      propionate side chain of heme, and makes pi-pi stacking and hydrophobic
      interactions with porphyrin plane. Interestingly, similar Arg-heme interactions
      are also found for periplasmic heme transporter, PhuT, suggesting that this is an
      example of a convergent evolution and one of the important interactions for
      bacterial heme transportation. Heme titration, heme binding kinetics, and the
      crystal structures of wild-type and Y75A proteins show that, although Tyr75 is
      primarily important for heme capturing, other interactions with Arg40, Arg144,
      and hydrophobic residues also contribute for heme acquisition. We also found that
      HasAypt can form a dimer in solution. The structure of the domain-swapped Y75A
      HasAypt dimer shows the presence of two low-spin heme molecules coordinated with
      His84 and His140, and displacement of the Arg40 loop of dimeric Y75A HasAypt
      results in deformation of the heme-binding pocket. A similar rearrangement of the
      distal heme loop might occur in heme transfer from HasAypt to HasRypt. 

PMID- 26210322
TI  - Phenolic wastewater treatment through extractive recovery coupled with
      biodegradation in a two-phase partitioning membrane bioreactor.
AB  - A two-phase partitioning membrane bioreactor (TPPMB) was designed and operated
      for treatment of high strength phenolic wastewater through extraction/stripping
      and concomitant biodegradation. Tributyl phosphate dissolved in kerosene was used
      as the organic phase, sodium hydroxide as the stripping phase and Pseudomonas
      putida for biodegradation. In a semi-dispersive approach, organic phase dispersed
      in the stripping solution was contacted with wastewater through semi-permeable
      membranes for removal of phenol from wastewater, while the microorganisms were
      inoculated directly into the wastewater for biodegradation. The TPPMB exhibited
      high phenol removal rates, and phenol concentrations of 1000-3000mg/L were
      reduced to undetected amounts within 2-4h. Up to 80% phenol was recovered through
      extraction, while the remaining was metabolized by the microorganisms. Phenol
      recovery in the TPPMB was enhanced by increasing the mass transfer rate of phenol
      through the membranes, and it was also estimated that phenol diffusion through
      the aqueous boundary layer on the tube side was the rate limiting step. The
      flexibility in adjusting inoculation time in the TPPMB prevented microorganisms
      from adverse effects of substrate inhibition, which facilitated complete removal
      of phenol from the wastewater. TPPMB retained the advantages of both solvent
      extraction and biodegradation, and it can be highly promising for the treatment
      of toxic industrial wastewater. 

PMID- 26210323
TI  - Recovery of Cu(II) by chemical reduction using sodium dithionite.
AB  - Wastewaters containing Cu(II) along with ligands are ubiquitous in various
      industrial sectors. Efficacy of treatment processes for copper removal,
      especially precipitation, is greatly debilitated by ligands. Chemical reduction
      being commonly employed for production of metal nanoparticles has also been used
      for removing copper. Addition of ammonia was reported to be essential for
      improving copper reduction efficiency by increasing copper solubility at alkaline
      pH values. In this study, chemical reduction was employed to treat ligand
      containing wastewater, exploiting the fact that ligands and metals are coexisted
      in many wastewaters. Result shows that copper ions were removed by either
      reduction or precipitation mechanisms depending on pH, type of ligands, and
      mixing condition. Complete copper reduction/removal was achieved under optimal
      condition. The lowest removal efficiency observed at pH 9.0 for ammonia system is
      due to formation of nano-sized particles, which are readily to pass through
      0.45MUm filter used for sample pretreatment before copper analysis. Instead of
      producing metallic copper, cuprous and copper oxide are identified in the samples
      collected from ammonia system and EDTA system, respectively. Re-oxidation of
      metallic copper particles by atmospheric oxygen during sample handling or
      incomplete reduction of Cu(II) ions during reduction process might be the cause.
      Finally, reduction process was applied to treat real wastewater, achieving
      complete removal of copper but only 10% of nickel. 

PMID- 26210324
TI  - Supercritical water oxidation of a model fecal sludge without the use of a co
      fuel.
AB  - A continuous supercritical water oxidation reactor was designed and constructed
      to investigate the conversion of a feces simulant without the use of a co-fuel.
      The maximum reactor temperature and waste conversion was determined as a function
      of stoichiometric excess of oxygen in order to determine factor levels for
      subsequent investigation. 48% oxygen excess showed the highest temperature with
      full conversion. Factorial analysis was then used to determine the effects of
      feed concentration, oxygen excess, inlet temperature, and operating pressure on
      the increase in the temperature of the reacting fluid as well as a newly defined
      non-dimensional number, NJa representing heat transfer efficiency. Operating
      pressure and stoichiometric excess oxygen were found to have the most significant
      impacts on NJa. Feed concentration had a significant impact on fluid temperature
      increase showing an average difference of 46.4 degrees C between the factorial
      levels. 

PMID- 26210325
TI  - Decreasing iron-related indexes without anaemia in a patient with genetic
      haemochromatosis.
AB  - Present case report refers to a 48-year-old man with genetic haemochromatosis
      (C282Y mut/mut) diagnosed at the age of 26. After aggressive iron depleting
      regimen carried out up to normalization of iron-related indexes, he received a
      maintenance regimen based on regular phlebotomies for about 20 years. In 2014, a
      marked reduction of both serum ferritin and transferrin saturation percent,
      without concomitant anaemia, was noted on two different occasions at 5-month
      interval. An obscure occult GI bleeding was suspected, but both upper and lower
      GI tract endoscopy were negative for abnormal findings, as also was a detailed
      abdominal US scan. The persistence of low iron-related indexes prompted the
      physicians to perform a videocapsule endoscopy, which showed an ulcerative
      bleeding lesion in the small bowel, not confirmed however by both anterograde and
      retrograde double-balloon enteroscopy. Further MRI and PET allowed the
      identification of a 3.5 cm large lesion, located outside the small bowel wall,
      suspected to be a gastrointestinal stromal tumour (GIST). A further laparoscopic
      procedure allowed the resection of 10 cm of midileum, which included the mass,
      fully consistent with GIST at pathology. 

PMID- 26210326
TI  - Here/In This Issue and There/Abstract Thinking: Neurosciences and (Child)
      Psychiatry.

PMID- 26210327
TI  - Teaching Cultural Formulation.

PMID- 26210328
TI  - Human Induced Pluripotent Stem Cells Re-Engineer the Study of Neurodevelopmental
      Disorders.

PMID- 26210329
TI  - Defining Cortical Structure in Adolescent Attention-Deficit/Hyperactivity
      Disorder.

PMID- 26210330
TI  - The Research Domain Criteria (RDoC) Project and Studies of Risk and Resilience in
      Maltreated Children.
AB  - OBJECTIVE: The Research Domain Criteria (RDoC) project was initiated to develop,
      for research purposes, new ways of classifying mental disorders based on
      dimensions of observable behavior and neurobiological measures. This article
      reviews the rationale behind the RDoC program, its goals, and central tenets;
      discusses application of an RDoC framework to research with maltreated children;
      and highlights some clinical implications of this work. METHOD: Published RDoC
      papers were reviewed, together with relevant preclinical and clinical studies
      that guide our work on risk and resilience in maltreated children. RESULTS: The
      ultimate long-term goal of the RDoC initiative is precision medicine in
      psychiatry. In the interim, the RDoC initiative provides a framework to organize
      research to help develop the database required to derive a new psychiatric
      nomenclature that can appropriately match treatments to patients. The primary
      focus of RDoC is on neural circuitry, with levels of analyses that span from
      molecules to behavior. There has been some concern that the RDoC framework is
      reductionist, with an overemphasis on neural circuits and genetics; however, the
      briefly reviewed, burgeoning literature on neuroplasticity and epigenetics
      highlights that this concern is unwarranted, as one cannot study neural circuits
      and genetics without considering experience. CONCLUSION: The study of maltreated
      children has a number of advantages for the RDoC project, including the
      following: study of a subset of patients who are often not responsive to standard
      interventions; examination of a relatively homogenous sample with onset of
      psychopathology proposed to be associated with stress-related mechanisms; and
      well-established, relevant animal models to facilitate translational research.

PMID- 26210331
TI  - Clinical Implications of a Dimensional Approach: The Normal:Abnormal Spectrum of
      Early Irritability.
AB  - OBJECTIVE: The importance of dimensional approaches is widely recognized, but an
      empirical base for clinical application is lacking. This is particularly true for
      irritability, a dimensional phenotype that cuts across many areas of
      psychopathology and manifests early in life. We examine longitudinal, dimensional
      patterns of irritability and their clinical import in early childhood. METHOD:
      Irritability was assessed longitudinally over an average of 16 months in a
      clinically enriched, diverse community sample of preschoolers (N = 497; mean =
      4.2 years; SD = 0.8). Using the Temper Loss scale of the Multidimensional
      Assessment Profile of Disruptive Behavior (MAP-DB) as a developmentally sensitive
      indicator of early childhood irritability, we examined its convergent/divergent,
      clinical, and incremental predictive validity, and modeled its linear and
      nonlinear associations with clinical risk. RESULTS: The Temper Loss scale
      demonstrated convergent and divergent validity to child and maternal factors. In
      multivariate analyses, Temper Loss predicted mood (separation anxiety disorder
      [SAD], generalized anxiety disorder [GAD], and depression/dysthymia), disruptive
      (oppositional defiant disorder [ODD], attention-deficit/hyperactivity disorder
      [ADHD], and conduct disorder [CD]) symptoms. Preschoolers with even mildly
      elevated Temper Loss scale scores showed substantially increased risk of symptoms
      and disorders. For ODD, GAD, SAD, and depression, increases in Temper Loss scale
      scores at the higher end of the dimension had a greater impact on symptoms
      relative to increases at the lower end. Temper Loss scale scores also showed
      incremental validity over DSM-IV disorders in predicting subsequent impairment.
      Finally, accounting for the substantial heterogeneity in longitudinal patterns of
      Temper Loss significantly improved prediction of mood and disruptive symptoms.
      CONCLUSION: Dimensional, longitudinal characterization of irritability informs
      clinical prediction. A vital next step will be empirically generating parameters
      for the incorporation of dimensional information into clinical decision-making
      with reasonable certainty.

PMID- 26210332
TI  - Normative Irritability in Youth: Developmental Findings From the Great Smoky
      Mountains Study.
AB  - OBJECTIVE: The goal of this study is to examine the developmental epidemiology of
      normative irritability and its tonic and phasic components in a longitudinal
      community sample of youth. METHOD: Eight waves of data from the prospective,
      community Great Smoky Mountains Study (6,674 assessments of 1,420 participants)
      were used, covering children in the community 9 to 16 years of age. Youth and 1
      parent were interviewed using the Child and Adolescent Psychiatric Assessment to
      assess tonic (touchy/easily annoyed, irritable mood, angry or resentful) and
      phasic (temper tantrums or anger outbursts) components of irritability, including
      frequency, duration, onset, and cross-context variability. RESULTS: At any given
      point in childhood/adolescence, 51.4% (standard error [SE] = 1.4) of participants
      reported phasic irritability, 28.3% (SE = 1.2) reported tonic irritability, and
      22.8% (SE = 1.1) reported both. These prevalence levels decreased with age but
      did not vary by sex. The overlap between tonic and phasic irritability was high
      (odds ratio = 5.8, 95% CI = 3.3-10.5, p < .0001), with little evidence of tonic
      occurring without phasic irritability. Both tonic and phasic irritability
      predicted one another over time, supporting both heterotypic and homotypic
      continuity. Low levels of either tonic or phasic irritability increased risk for
      disrupted functioning including service use, school suspensions, parental burden,
      and emotional symptoms both concurrently and at 1-year follow-up. CONCLUSION:
      Irritability is relatively common, decreases with age but does not vary by sex,
      and at almost any level is associated with increased risk of disrupted
      functioning. Its relative components frequently overlap, although irritable
      outbursts are more common than irritable mood. Irritability appears to be a high
      priority transdiagnostic marker for screening children in need of clinical
      attention.

PMID- 26210333
TI  - Child Gain Approach and Loss Avoidance Behavior: Relationships With Depression
      Risk, Negative Mood, and Anhedonia.
AB  - OBJECTIVE: Reduced reward responsiveness and altered response to loss of reward
      are observed in adults with major depressive disorder (MDD) and adolescents at
      increased risk for MDD based on family history. However, it is unclear whether
      altered behavioral responsiveness to reward/loss is a lifelong marker of MDD
      risk, which is evident before the normative adolescent increase in incentive
      responding. METHOD: Healthy 7- to 10-year-old children of mothers with MDD (high
      risk: n = 27) or without MDD (low risk: n = 42) performed 2 signal detection
      tasks assessing response bias toward reward (approach) and away from loss
      (avoidance). Differences in approach/avoidance were related to MDD risk, child
      general depressive symptoms (maternal report), child-reported anhedonic symptoms,
      and child-reported negative mood symptoms via repeated-measures analysis of
      variance. RESULTS: MDD risk did not significantly relate to gain approach or loss
      avoidance. However, within high-risk children, higher numbers of maternal
      depressive episodes predicted blunted loss avoidance. Blunted gain approach was
      related to elevated anhedonic symptoms, whereas enhanced loss avoidance was
      related to elevated negative mood. Elevated negative mood was further related to
      blunted gain approach in high-risk children but related to enhanced gain approach
      in low-risk children. CONCLUSION: In children, individual differences in specific
      depressive symptoms and recurrence of maternal depression significantly predicted
      gain approach/loss avoidance, but the presence/absence of maternal MDD did not.
      Child depressive symptoms characterized by low positive affect (anhedonia) were
      related to blunted gain responsiveness, whereas elevated depressed/negative mood
      was related to enhanced loss responsiveness. Findings suggest that relations
      between gain approach and negative mood may be an important distinction between
      those at high versus low risk for MDD.

PMID- 26210335
TI  - Thinner Medial Temporal Cortex in Adolescents With Attention
      Deficit/Hyperactivity Disorder and the Effects of Stimulants.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) has been associated
      with widespread changes in cortical thickness (CT). Findings have been
      inconsistent, however, possibly due to age differences between samples. Cortical
      changes have also been suggested to be reduced or to disappear with stimulant
      treatment. We investigated differences in CT between adolescents/young adults
      with and without ADHD in the largest ADHD sample to date, the NeuroIMAGE sample.
      Second, we investigated how such differences were related to age and stimulant
      treatment. METHOD: Participants (participants with ADHD = 306; healthy controls =
      184, 61% male, 8-28 years of age, mean age = 17 years) underwent structural
      magnetic resonance imaging. Participants and pharmacies provided detailed
      information regarding lifetime stimulant treatment, including cumulative intake
      and age of treatment initiation and cessation. Vertexwise statistics were
      performed in Freesurfer, modeling the main effect of diagnosis on CT and its
      interaction with age. Effects of stimulant treatment parameters on CT were
      modeled within the sample with ADHD. RESULTS: After correction for multiple
      comparisons, participants with ADHD showed decreased medial temporal CT in both
      left (pCLUSTER = .008) and right (pCLUSTER = .038) hemispheres. These differences
      were present across different ages and were associated with symptoms of
      hyperactivity and prosocial behavior. There were no age-by-diagnosis interaction
      effects. None of the treatment parameters predicted CT within ADHD. CONCLUSION:
      Individuals with ADHD showed thinner bilateral medial temporal cortex throughout
      adolescence and young adulthood compared to healthy controls. We found no
      association between CT and stimulant treatment. The cross-sectional design of the
      current study warrants cautious interpretation of the findings.

PMID- 26210334
TI  - Adolescent Eating Disorders Predict Psychiatric, High-Risk Behaviors and Weight
      Outcomes in Young Adulthood.
AB  - OBJECTIVE: To investigate whether anorexia nervosa (AN), bulimia nervosa (BN),
      binge eating disorder (BED), and other specified feeding and eating disorders
      (OSFED), including purging disorder (PD), subthreshold BN, and BED at ages 14 and
      16 years, are prospectively associated with later depression, anxiety disorders,
      alcohol and substance use, and self-harm. METHOD: Eating disorders were
      ascertained at ages 14 and 16 years in 6,140 youth at age 14 (58% of those
      eligible) and 5,069 at age 16 (52% of those eligible) as part of the prospective
      Avon Longitudinal Study of Parents and Children (ALSPAC). Outcomes (depression,
      anxiety disorders, binge drinking, drug use, deliberate self-harm, weight status)
      were measured using interviews and questionnaires about 2 years after predictors.
      Generalized estimating equation models adjusting for gender, socio-demographic
      variables, and prior outcome were used to examine prospective associations
      between eating disorders and each outcome. RESULTS: All eating disorders were
      predictive of later anxiety disorders. AN, BN, BED, PD, and OSFED were
      prospectively associated with depression (respectively AN: odds ratio [OR] =
      1.39, 95% CI = 1.00-1.94; BN: OR = 3.39, 95% CI = 1.25-9.20; BED: OR = 2.00, 95%
      CI = 1.06-3.75; and PD: OR = 2.56, 95% CI = 1.38-4.74). All eating disorders but
      AN predicted drug use and deliberate self-harm (BN: OR = 5.72, 95% CI = 2.22
      14.72; PD: OR = 4.88, 95% CI = 2.78-8.57; subthreshold BN: OR = 3.97, 95% CI =
      1.44-10.98; and subthreshold BED: OR = 2.32, 95% CI = 1.43-3.75). Although BED
      and BN predicted obesity (respectively OR = 3.58, 95% CI = 1.06-12.14 and OR =
      6.42, 95% CI = 1.69-24.30), AN was prospectively associated with underweight.
      CONCLUSIONS: Adolescent eating disorders, including subthreshold presentations,
      predict negative outcomes, including mental health disorders, substance use,
      deliberate self-harm, and weight outcomes. This study highlights the high public
      health and clinical burden of eating disorders among adolescents.

PMID- 26210336
TI  - Reduced Gyrification Is Related to Reduced Interhemispheric Connectivity in
      Autism Spectrum Disorders.
AB  - OBJECTIVE: Autism spectrum disorders (ASD) have been associated with atypical
      cortical gray and subcortical white matter development. Neurodevelopmental
      theories postulate that a relation between cortical maturation and structural
      brain connectivity may exist. We therefore investigated the development of
      gyrification and white matter connectivity and their relationship in individuals
      with ASD and their typically developing peers. METHOD: T1- and diffusion-weighted
      images were acquired from a representative sample of 30 children and adolescents
      with ASD (aged 8-18 years), and 29 typically developing children matched for age,
      sex, hand preference, and socioeconomic status. The FreeSurfer suite was used to
      calculate cortical volume, surface area, and gyrification index. Measures of
      structural connectivity were estimated using probabilistic tractography and tract
      based spatial statistics (TBSS). RESULTS: Left prefrontal and parietal cortex
      showed a relative, age-dependent decrease in gyrification index in children and
      adolescents with ASD compared to typically developing controls. This result was
      replicated in an age-and IQ-matched sample provided by the Autism Brain Imaging
      Data Exchange (ABIDE) initiative. Furthermore, tractography and TBSS showed a
      complementary pattern in which left prefrontal gyrification was negatively
      related to radial diffusivity in the forceps minor in participants with ASD.
      CONCLUSION: The present study builds on earlier findings of abnormal gyrification
      and structural connectivity in the prefrontal cortex in ASD. It provides a more
      comprehensive neurodevelopmental characterization of ASD, involving
      interdependent changes in microstructural white and cortical gray matter. The
      findings of related abnormal patterns of gyrification and white matter
      connectivity support the notion of the intertwined development of 2 major
      morphometric domains in ASD.

PMID- 26210337
TI  - Gray Matter Volume Decrease Distinguishes Schizophrenia From Bipolar Offspring
      During Childhood and Adolescence.
AB  - OBJECTIVE: There is increasing support toward the notion that schizophrenia and
      bipolar disorder share neurodevelopmental underpinnings, although areas of
      divergence remain. We set out to examine gray matter volume characteristics of
      child and adolescent offspring of patients with schizophrenia or bipolar disorder
      comparatively. METHOD: In this 2-center study, magnetic resonance structural
      neuroimaging data were acquired in 198 children and adolescents (aged 6-17
      years): 38 offspring of patients with schizophrenia, 77 offspring of patients
      with bipolar disorder, and 83 offspring of community controls. Analyses of global
      brain volumes and voxel-based morphometry (using familywise error correction)
      were conducted. RESULTS: There was an effect of group on total cerebral gray
      matter volume (F = 3.26, p = .041), driven by a decrease in offspring of patients
      with schizophrenia relative to offspring of controls (p = .035). At a voxel-based
      level, we observed an effect of group in the left inferior frontal
      cortex/anterior insula (F = 14.7, p < .001), which was driven by gray matter
      volume reduction in offspring of patients with schizophrenia relative to both
      offspring of controls (p = .044) and of patients with bipolar disorder (p <
      .001). No differences were observed between offspring of patients with bipolar
      disorder and offspring of controls in either global or voxel-based gray matter
      volumes. CONCLUSION: This first comparative study between offspring of patients
      with schizophrenia and bipolar disorder suggests that gray matter volume
      reduction in childhood and adolescence may be specific to offspring of patients
      with schizophrenia; this may index a greater neurodevelopmental impact of risk
      for schizophrenia relative to bipolar disorder during youth.

PMID- 26210338
TI  - Measuring the Neural Basis of Reward Anticipation and Reward Receipt in Attention
      Deficit/Hyperactivity Disorder: The Importance of Task Design.

PMID- 26210339
TI  - In Reply.

PMID- 26210341
TI  - Measuring clinical skills in agenda-mapping (EAGL-I).
AB  - OBJECTIVE: To develop and validate the Evaluation of AGenda-mapping skilL
      Instrument (EAGL-I). METHODS: EAGL-I was constructed after a literature review
      and piloting. Simulated consultation recordings were collected in a workshop with
      third-year medical students at three time points: once pre-teaching, twice post
      teaching. Three raters used EAGL-I to assess student agenda-mapping. We examined
      reliability, ability to detect change and predict full expression of patients'
      agendas. RESULTS: EAGL-I scores represented reliable assessment of agenda-mapping
      (Ep(2)=0.832; phi=0.675). Generalizability coefficients across items
      (Ep(2)=0.836) and raters (phi=0.797 two raters) were acceptable. A one-way
      repeated measure ANOVA with post hoc analysis found a statistically significant
      difference between the pre-teaching occasion of measurement and each post
      teaching occasion (p<0.001) and no significant difference between the two post
      teaching occasions (p=0.085). Multilevel logistic regression show scores predict
      expression of scripted hidden agendas irrespective of occasions, or patient
      scenario (n=60, p=0.005). CONCLUSION: Evidence of measure validation is shown.
      Reliability is optimised when two or more raters use EAGL-I and agenda-mapping
      has been taught. EAGL-I appears sensitive to change. Higher scores predict the
      likelihood that a patient will disclose their full agenda in a simulated
      environment. PRACTICE IMPLICATIONS: A validated tool for measuring agenda-mapping
      in teaching and research is now available.

PMID- 26210342
TI  - LEAP: A randomized-controlled trial of a lay-educator inpatient asthma education
      program.
AB  - OBJECTIVE: To evaluate the impact of LEAP, a volunteer-based, inpatient asthma
      education program for families of inner-city children with asthma. METHODS: 711
      children ages 2-17 years admitted with status asthmaticus were randomized to
      receive usual care or usual care plus a supplemental education intervention. Both
      groups completed a baseline interview. Trained volunteer lay educators conducted
      individualized bedside education with the intervention group. Primary outcome was
      attendance at a post-hospitalization follow-up visit 7-10 days after discharge.
      Secondary outcomes included parent-reported asthma management behaviors,
      symptoms, and self-efficacy scores from a one month follow-up interview. RESULTS:
      Post-hospitalization asthma clinic attendance was poor (38%), with no difference
      between groups. Families randomized to the intervention group were more likely to
      report use of a controller (OR 2.4, 95% CI 1.3-4.2, p<0.01) and a valved-holding
      chamber (OR 2.9, 95% CI 1.1-7.4, p=0.03), and were more likely to have an asthma
      action plan at follow up (OR 2.0, 95% CI 1.3-3.0, p<0.01). Asthma self-efficacy
      scores were significantly improved among those who received the intervention
      (p=0.04). CONCLUSIONS: Inpatient asthma education by trained lay volunteers was
      associated with improved asthma management behaviors. PRACTICE IMPLICATIONS: This
      novel volunteer-based program could have widespread implications as a sustainable
      model for asthma education.

PMID- 26210343
TI  - Holmium laser enucleation of the prostate for treatment for large-sized benign
      prostate hyperplasia; is it a realistic endourologic alternative in developing
      country?
AB  - OBJECTIVES: To assess the functional outcome and cumulative health-resource
      related cost of holmium laser enucleation of the prostate (HoLEP) in comparison
      with transvesical open prostatectomy (TVOP) in a developing country. METHODS:
      Matching of 92 HoLEP and 91 TVOP procedures was performed using resected prostate
      tissue weight as a sole matching criterion. Safety, efficacy, and accordingly
      health-related cost-efficiency of both procedures were statistically compared.
      RESULTS: Preoperative criteria and mean prostate size (166.7 +/- 49.7, 161.4 +/-
      35.7 ml) were similar in HoLEP and TVOP, respectively; however, HoLEP treated
      more comorbid patients. Blood transfusion was 2.1 and 26.1 % after HoLEP and
      TVOP, respectively (P = 0.001). Median time to catheter removal and hospital stay
      was 2 days after HoLEP and 5 and 9 days, respectively, after TVOP (P < 0.001). On
      modified Clavien scale, grade per grade, there was no statistically significant
      difference between the two groups apart from local wound complications in TVOP
      group. High-grade complications (>= grade 3) were reported in 3.2 and 6.5 % in
      HoLEP and TVOP, respectively (P = 0.49). Resected prostate tissue weight was
      independently associated with high-grade periprocedure complications (OR[95 %CI]
      1.22[1.02:1.49], P = 0.03). Last follow-up symptom score, peak urine flow rate,
      residual urine, % PSA reduction, and need for reoperation were comparable between
      the two groups. HoLEP costs the hospital in the first 3 months 4111.8EP (575US$)
      versus 4305.4EP (602US$) for TVOP (P = 0.09). CONCLUSION: In high-volume
      hospital, HoLEP procedure seems to be equally safe and effective as TVOP with the
      advantages of minimally invasive procedures. Two years after adopting the
      technique, HoLEP equally costs the hospital as TVOP. Significant hospital cost
      savings are anticipated in subsequent cases.

PMID- 26210344
TI  - Mortality and flexible ureteroscopy: analysis of six cases.
AB  - PURPOSE: Advancements in the endourological equipment have made retrograde
      intrarenal surgery (RIRS) an attractive, widespread technique, capable of
      competing with traditional shock wave lithotripsy and percutaneous
      nephrolithotomy. Since the complication rate is generally low, even less is known
      about dramatic and fatal complications after RIRS. METHODS: We performed a survey
      asking 11 experienced endourologists to review their RIRS series and report the
      cases of mortality to their best knowledge. RESULTS: Six urologists reported on
      six fatal cases. In three cases, a history of urinary tract infections was
      present. Four patients died from urosepsis, one due to an anesthetic and one due
      to hemorrhagic complication. The use of ureteral access sheath was not common.
      CONCLUSION: Even respecting the standards of care, it may happen that physicians
      are occasionally tempted to overdo for their patients, sometimes skipping safety
      rules with an inevitable increase in risks. Despite the fact that RIRS has become
      a viable option for the treatment of the majority of kidney stones, its
      complication rates remain low. Nevertheless, rare fatal events may occur,
      especially in complex cases with a history of urinary tract infections, and
      advanced neurological diseases.

PMID- 26210345
TI  - Rhodnius prolixus smells repellents: Behavioural evidence and test of present and
      potential compounds inducing repellency in Chagas disease vectors.
AB  - Insect repellents are known since many decades ago and constitute a major tool
      for personal protection against the biting of mosquitoes. Despite their wide use,
      the understanding of why and how repellents repel is relatively recent. In
      particular, the question about to what extent insects other than mosquitoes are
      repulsed by repellents remains open. We developed a series of bioassays aimed to
      test the performance of well established as well as potential repellent molecules
      on the Chagas disease vector Rhodnius prolixus. Besides testing their ability to
      prevent biting, we tested the way in which they act, i.e., by obstructing the
      detection of attractive odours or by themselves. By using three different
      experimental protocols (host-biting, open-loop orientation to odours and heat
      triggered proboscis extension response) we show that DEET repels bugs both in the
      presence and in the absence of host-associated odours but only at the highest
      quantities tested. Piperidine was effective with or without a host and icaridine
      only repelled in the absence of a living host. Three other molecules recently
      proposed as potential repellents due to their affinity to the Ir40a(+) receptor
      (which is also activated by DEET) did not evoke significant repellency. Our work
      provides novel experimental tools and sheds light on the mechanism behind
      repellency in haematophagous bugs. 

PMID- 26210346
TI  - Introduction to the Symposium--Chemicals that Organize Ecology: Towards a Greater
      Integration of Chemoreception, Neuroscience, Organismal Biology, and Chemical
      Ecology.

PMID- 26210347
TI  - Coping Responses Among Hospice Family Caregivers: A Confirmatory Factor Analysis.
AB  - CONTEXT: Hospice family caregivers must often cope with significant stressors.
      Research into the ways caregivers attempt to cope with these stressors has been
      challenged by pronounced difficulties conceptualizing, measuring, and
      categorizing caregiver coping. OBJECTIVES: The purpose of this study was to begin
      addressing these challenges by determining the structure of coping among hospice
      family caregivers. METHODS: Hospice family caregivers (n = 223) residing in the
      midsouthern U.S. completed the Ways of Coping Questionnaire as part of a cross
      sectional survey. To examine the validity of various coping response factor
      structures, researchers conducted multiple confirmatory factor analyses. RESULTS:
      Although individual coping behaviors were able to be sorted into broader "ways of
      coping" (i.e., first-order factors), data did not support the further grouping of
      ways of coping into more general "families of coping" (i.e., second-order
      factors). Folkman and Lazarus's proposed structure of coping, which comprises
      eight first-order factors or subscales, better fit the data than the tested
      alternatives. CONCLUSION: Despite its broad appeal, grouping ways of coping
      responses into families of coping based on the presupposed nature of the
      responses (e.g., positive or negative) lacked empirical support for this sample
      of hospice family caregivers, which suggests that relying on families of coping
      may oversimplify complex responses from caregivers. Rather than trying to
      characterize coping responses into broader families, hospice support for
      caregiver coping strategies may be more effective when based on individualized
      assessments of each caregiver's ways of coping and the consequences of those
      coping responses on their quality of life.

PMID- 26210348
TI  - Impact of Smoking Cessation on Subsequent Pain Intensity Among Chronically Ill
      Veterans Enrolled in a Smoking Cessation Trial.
AB  - CONTEXT: Prior cross-sectional studies have reported greater pain intensity among
      persistent smokers compared with nonsmokers or former smokers; yet, few
      prospective studies have examined how smoking abstinence affects pain intensity.
      OBJECTIVES: To determine the impact of smoking cessation on subsequent pain
      intensity in smokers with chronic illness enrolled in a smoking cessation trial.
      METHODS: We recruited veteran smokers with chronic illness (heart disease,
      cancer, chronic obstructive pulmonary disease, diabetes, or hypertension) for a
      randomized controlled smoking cessation trial and prospectively examined pain
      intensity and smoking status. Participants (n = 380) were asked to rate their
      pain in the past week from 0 to 10 at baseline and the five-month follow-up. The
      primary outcome measure was self-reported pain intensity at the five-month follow
      up survey. Self-reported smoking status was categorized as an abstainer if
      patients reported no cigarettes in the seven days before the follow-up survey.
      RESULTS: In unadjusted analyses, abstainers reported significantly lower pain
      levels at the five-month follow-up compared with patients who continued to smoke
      (parameter estimate = -1.07; 95% CI = -1.77, -0.36). In multivariable modeling,
      abstaining from cigarettes was not associated with subsequent pain intensity at
      five-month follow-up (parameter estimate = -0.27; 95% CI = -0.79, 0.25).
      CONCLUSION: Participants who were classified as abstainers did not report
      significantly different levels of pain intensity than patients who continued to
      smoke. Future studies should expand on our findings and monitor pain intensity in
      smoking cessation trials. TRIAL REGISTRATION: ClinicalTrials.govNCT00448344.

PMID- 26210351
TI  - Elaborations for the Validation of Causal Bridging Inferences in Text
      Comprehension.
AB  - The validation model of causal bridging inferences proposed by Singer and
      colleagues (e.g., Singer in Can J Exp Psychol, 47(2):340-359, 1993) claims that
      before a causal bridging inference is accepted, it must be validated by existing
      knowledge. For example, to understand "Dorothy took the aspirins. Her pain went
      away," one first computes a mediating idea RELIEVE [ASPIRIN, PAIN]. Then, the
      truth of it is validated on the basis of existing knowledge. The present study
      examined the hypothesis that a causal inference would be drawn and validated even
      when validating knowledge is not familiar or available because elaborations are
      made to retrieve or construct such knowledge. Experiment 1 showed that people
      tend to judge naturalness of a text based on causal relations and that causality
      was indeed recognized in those texts in which the antecedent sentence and the
      consequence sentence are not linked by familiar knowledge. Experiment 2, which
      measured sentence reading times, showed that while sentence processing times were
      longer for such texts than texts involving familiar knowledge, there was no
      difference between these texts in reading the subsequent sentence describing the
      validating idea. These results provided evidence supporting elaboration as well
      as validation of causal bridging inferences. 

PMID- 26210349
TI  - Effects of amorphous silica coating on cerium oxide nanoparticles induced
      pulmonary responses.
AB  - Recently cerium compounds have been used in a variety of consumer products,
      including diesel fuel additives, to increase fuel combustion efficiency and
      decrease diesel soot emissions. However, cerium oxide (CeO2) nanoparticles have
      been detected in the exhaust, which raises a health concern. Previous studies
      have shown that exposure of rats to nanoscale CeO2 by intratracheal instillation
      (IT) induces sustained pulmonary inflammation and fibrosis. In the present study,
      male Sprague-Dawley rats were exposed to CeO2 or CeO2 coated with a nano layer of
      amorphous SiO2 (aSiO2/CeO2) by a single IT and sacrificed at various times post
      exposure to assess potential protective effects of the aSiO2 coating. The first
      acellular bronchoalveolar lavage (BAL) fluid and BAL cells were collected and
      analyzed from all exposed animals. At the low dose (0.15mg/kg), CeO2 but not
      aSiO2/CeO2 exposure induced inflammation. However, at the higher doses, both
      particles induced a dose-related inflammation, cytotoxicity, inflammatory
      cytokines, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP at 1day
      post-exposure. Morphological analysis of lung showed an increased inflammation,
      surfactant and collagen fibers after CeO2 (high dose at 3.5mg/kg) treatment at
      28days post-exposure. aSiO2 coating significantly reduced CeO2-induced
      inflammatory responses in the airspace and appeared to attenuate phospholipidosis
      and fibrosis. Energy dispersive X-ray spectroscopy analysis showed Ce and
      phosphorous (P) in all particle-exposed lungs, whereas Si was only detected in
      aSiO2/CeO2-exposed lungs up to 3days after exposure, suggesting that aSiO2
      dissolved off the CeO2 core, and some of the CeO2 was transformed to CePO4 with
      time. These results demonstrate that aSiO2 coating reduce CeO2-induced
      inflammation, phospholipidosis and fibrosis. 

PMID- 26210350
TI  - Malignant human cell transformation of Marcellus Shale gas drilling flow back
      water.
AB  - The rapid development of high-volume horizontal hydraulic fracturing for mining
      natural gas from shale has posed potential impacts on human health and
      biodiversity. The produced flow back waters after hydraulic stimulation are known
      to carry high levels of saline and total dissolved solids. To understand the
      toxicity and potential carcinogenic effects of these wastewaters, flow back
      waters from five Marcellus hydraulic fracturing oil and gas wells were analyzed.
      The physicochemical nature of these samples was analyzed by inductively coupled
      plasma mass spectrometry and scanning electron microscopy/energy dispersive X-ray
      spectroscopy. A cytotoxicity study using colony formation as the endpoint was
      carried out to define the LC50 values of test samples using human bronchial
      epithelial cells (BEAS-2B). The BEAS-2B cell transformation assay was employed to
      assess the carcinogenic potential of the samples. Barium and strontium were among
      the most abundant metals in these samples and the same metals were found to be
      elevated in BEAS-2B cells after long-term treatment. BEAS-2B cells treated for
      6weeks with flow back waters produced colony formation in soft agar that was
      concentration dependent. In addition, flow back water-transformed BEAS-2B cells
      show better migration capability when compared to control cells. This study
      provides information needed to assess the potential health impact of post
      hydraulic fracturing flow back waters from Marcellus Shale natural gas mining. 

PMID- 26210352
TI  - What Can an Adoption Study Tell Us About the Effect of Prenatal Environment on a
      Trait?
AB  - Adoption studies provide possibilities for estimating the extent to which
      prenatal environmental events account for individual differences on a trait.
      Correlations with birth mothers but not adoptive mothers suggest the presence of
      genetic or prenatal environmental effects; higher correlations with birth mothers
      than with birth fathers suggest the presence of the latter. Changes over time may
      also be relevant. The concepts involved are illustrated with parent-child IQ
      correlations from the Texas and Colorado Adoption Projects.

PMID- 26210354
TI  - Ecological relevance of current water quality assessment unit designations in
      impaired rivers.
AB  - Managers often nest sections of water bodies together into assessment units (AUs)
      to monitor and assess water quality criteria. Ideally, AUs represent an extent of
      waters with similar ecological, watershed, habitat and land-use conditions and no
      overlapping characteristics with other waters. In the United States, AUs are
      typically based on political or hydrologic boundaries rather than on ecologically
      relevant features, so it can be difficult to detect changes in impairment status.
      Our goals were to evaluate if current AU designation criteria of an impaired
      water body in southeastern Idaho, USA that, like many U.S. waters, has three
      quarters of its mainstem length divided into two AUs. We focused our evaluation
      in southeastern Idaho's Portneuf River, an impaired river and three-quarters of
      the river is divided into two AUs. We described biological and environmental
      conditions at multiple reaches within each AU. We used these data to (1) test if
      variability at the reach-scale is greater within or among AUs and, (2) to
      evaluate alternate AU boundaries based on multivariate analyses of reach-scale
      data. We found that some biological conditions had greater variability within an
      AU than between AUs. Multivariate analyses identified alternative, 2- and 3
      group, AUs that reduced this variability. Our results suggest that the current AU
      designations in the mainstem Portneuf River contain ecologically distinct
      sections of river and that the existing AU boundaries should be reconsidered in
      light of the ecological conditions measured at the reach scale. Variation in
      biological integrity within designated AUs may complicate water quality and
      biological assessments, influence management decisions or affect where monitoring
      or mitigation resources are directed. 

PMID- 26210353
TI  - Biology of the bone marrow microenvironment and myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are characterized by cytopenias resulting from
      ineffective hematopoiesis with a predisposition to transform to acute myeloid
      leukemia (AML). Recent evidence suggests that the hematopoietic stem cell
      microenvironment contributes to the pathogenesis of MDS. Inflammation and hypoxia
      within the bone marrow are key regulators of hematopoietic stem and progenitor
      cells that can lead to several bone marrow failure syndromes, including MDS. In
      this brief review, we provide an overview of the clinical and molecular features
      of MDS, the bone marrow microenvironment, and specific pathways that lead to
      abnormal blood cell development in MDS. Characterization of key steps in the
      pathogenesis of MDS will lead to new approaches to treat patients with this
      disease. 

PMID- 26210356
TI  - Dynamics of ubiquitin-mediated signalling: insights from mathematical modelling
      and experimental studies.
AB  - Post-translational modification of cellular proteins by ubiquitin is a pivotal
      regulatory event that controls not only protein degradation, but also a variety
      of non-proteolytic functions. Ubiquitination is involved in a broad array of
      physiological processes, and its dysregulation has been associated with many
      human diseases, including neuronal disorders and cancers. Ubiquitin-mediated
      signalling has thus come to the forefront of biomedical research. It is
      increasingly apparent that ubiquitination is a highly complex and dynamic
      process, evidenced by a myriad of ways of ubiquitin chain formation, tightly
      regulatory mechanisms involving E3 ligases and deubiquitinating enzymes and
      extensive crosstalk with other post-translational modifications. To unravel the
      complexity of ubiquitination and understand the dynamic properties of ubiquitin
      mediated signalling are challenging, but critical topics in ubiquitin research,
      which will undoubtedly benefit our effort in developing strategies that could
      target ubiquitin signalling for therapeutics. Computational modelling and model
      based approaches are emerging as promising tools that help tackle the complexity
      and provide useful frameworks for quantitative and dynamical analysis of
      ubiquitin signalling. In this article, I will discuss recent advances in our
      understanding of the dynamic behaviour of ubiquitination from both theoretical
      and experimental studies, and aspects of ubiquitin signalling that may have major
      dynamical consequences. It is expected the discussed issues will be of relevant
      interest to both the ubiquitin and systems biology fields.

PMID- 26210355
TI  - Numb Chin Syndrome.
AB  - "Numb chin syndrome" (NCS) refers to new-onset numbness of the lower lip and chin
      within the distribution of the mental or inferior alveolar nerves. While this
      focal numbness may be downplayed or even overlooked by patients and clinicians,
      in the right clinical scenario this may be the presenting symptom of an
      underlying malignancy. In the absence of any obvious, temporally related dental
      cause, there are certain conditions that clinicians should consider including
      orofacial and systemic malignancies as well as several inflammatory disorders.
      Thorough diagnostic evaluation should always be performed when no clear cause is
      evident. This paper will discuss the differential, recommended evaluations, and
      the prognosis, for a patient presenting with NCS. 

PMID- 26210357
TI  - Evaluation of somatic copy number estimation tools for whole-exome sequencing
      data.
AB  - Whole-exome sequencing (WES) has become a standard method for detecting genetic
      variants in human diseases. Although the primary use of WES data has been the
      identification of single nucleotide variations and indels, these data also offer
      a possibility of detecting copy number variations (CNVs) at high resolution.
      However, WES data have uneven read coverage along the genome owing to the target
      capture step, and the development of a robust WES-based CNV tool is challenging.
      Here, we evaluate six WES somatic CNV detection tools: ADTEx, CONTRA, Control
      FREEC, EXCAVATOR, ExomeCNV and Varscan2. Using WES data from 50 kidney
      chromophobe, 50 bladder urothelial carcinoma, and 50 stomach adenocarcinoma
      patients from The Cancer Genome Atlas, we compared the CNV calls from the six
      tools with a reference CNV set that was identified by both single nucleotide
      polymorphism array 6.0 and whole-genome sequencing data. We found that these
      algorithms gave highly variable results: visual inspection reveals significant
      differences between the WES-based segmentation profiles and the reference
      profile, as well as among the WES-based profiles. Using a 50% overlap criterion,
      13-77% of WES CNV calls were covered by CNVs from the reference set, up to 21% of
      the copy gains were called as losses or vice versa, and dramatic differences in
      CNV sizes and CNV numbers were observed. Overall, ADTEx and EXCAVATOR had the
      best performance with relatively high precision and sensitivity. We suggest that
      the current algorithms for somatic CNV detection from WES data are limited in
      their performance and that more robust algorithms are needed. 

PMID- 26210358
TI  - VCF-Miner: GUI-based application for mining variants and annotations stored in
      VCF files.
AB  - Next-generation sequencing platforms are widely used to discover variants
      associated with disease. The processing of sequencing data involves read
      alignment, variant calling, variant annotation and variant filtering. The
      standard file format to hold variant calls is the variant call format (VCF) file.
      According to the format specifications, any arbitrary annotation can be added to
      the VCF file for downstream processing. However, most downstream analysis
      programs disregard annotations already present in the VCF and re-annotate
      variants using the annotation provided by that particular program. This precludes
      investigators who have collected information on variants from literature or other
      sources from including these annotations in the filtering and mining of variants.
      We have developed VCF-Miner, a graphical user interface-based stand-alone tool,
      to mine variants and annotation stored in the VCF. Powered by a MongoDB database
      engine, VCF-Miner enables the stepwise trimming of non-relevant variants. The
      grouping feature implemented in VCF-Miner can be used to identify somatic
      variants by contrasting variants in tumor and in normal samples or to identify
      recessive/dominant variants in family studies. It is not limited to human data,
      but can also be extended to include non-diploid organisms. It also supports copy
      number or any other variant type supported by the VCF specification. VCF-Miner
      can be used on a personal computer or large institutional servers and is freely
      available for download from http://bioinformaticstools.mayo.edu/research/vcf
      miner/. 

PMID- 26210359
TI  - Combining knowledge- and data-driven methods for de-identification of clinical
      narratives.
AB  - A recent promise to access unstructured clinical data from electronic health
      records on large-scale has revitalized the interest in automated de
      identification of clinical notes, which includes the identification of mentions
      of Protected Health Information (PHI). We describe the methods developed and
      evaluated as part of the i2b2/UTHealth 2014 challenge to identify PHI defined by
      25 entity types in longitudinal clinical narratives. Our approach combines
      knowledge-driven (dictionaries and rules) and data-driven (machine learning)
      methods with a large range of features to address de-identification of specific
      named entities. In addition, we have devised a two-pass recognition approach that
      creates a patient-specific run-time dictionary from the PHI entities identified
      in the first step with high confidence, which is then used in the second pass to
      identify mentions that lack specific clues. The proposed method achieved the
      overall micro F1-measures of 91% on strict and 95% on token-level evaluation on
      the test dataset (514 narratives). Whilst most PHI entities can be reliably
      identified, particularly challenging were mentions of Organizations and
      Professions. Still, the overall results suggest that automated text mining
      methods can be used to reliably process clinical notes to identify personal
      information and thus providing a crucial step in large-scale de-identification of
      unstructured data for further clinical and epidemiological studies. 

PMID- 26210360
TI  - Predicting changes in systolic blood pressure using longitudinal patient records.
AB  - OBJECTIVE: This paper introduces a model that predicts future changes in systolic
      blood pressure (SBP) based on structured and unstructured (text-based)
      information from longitudinal clinical records. METHOD: For each patient, the
      clinical records are sorted in chronological order and SBP measurements are
      extracted from them. The model predicts future changes in SBP based on the
      preceding clinical notes. This is accomplished using least median squares
      regression on salient features found using a feature selection algorithm.
      RESULTS: Using the prediction model, a correlation coefficient of 0.47 is
      achieved on unseen test data (p<.0001). This is in contrast to a baseline
      correlation coefficient of 0.39.

PMID- 26210361
TI  - Ease of adoption of clinical natural language processing software: An evaluation
      of five systems.
AB  - OBJECTIVE: In recognition of potential barriers that may inhibit the widespread
      adoption of biomedical software, the 2014 i2b2 Challenge introduced a special
      track, Track 3 - Software Usability Assessment, in order to develop a better
      understanding of the adoption issues that might be associated with the state-of
      the-art clinical NLP systems. This paper reports the ease of adoption assessment
      methods we developed for this track, and the results of evaluating five clinical
      NLP system submissions. MATERIALS AND METHODS: A team of human evaluators
      performed a series of scripted adoptability test tasks with each of the
      participating systems. The evaluation team consisted of four "expert evaluators"
      with training in computer science, and eight "end user evaluators" with mixed
      backgrounds in medicine, nursing, pharmacy, and health informatics. We assessed
      how easy it is to adopt the submitted systems along the following three
      dimensions: communication effectiveness (i.e., how effective a system is in
      communicating its designed objectives to intended audience), effort required to
      install, and effort required to use. We used a formal software usability testing
      tool, TURF, to record the evaluators' interactions with the systems and 'think
      aloud' data revealing their thought processes when installing and using the
      systems and when resolving unexpected issues. RESULTS: Overall, the ease of
      adoption ratings that the five systems received are unsatisfactory. Installation
      of some of the systems proved to be rather difficult, and some systems failed to
      adequately communicate their designed objectives to intended adopters. Further,
      the average ratings provided by the end user evaluators on ease of use and ease
      of interpreting output are -0.35 and -0.53, respectively, indicating that this
      group of users generally deemed the systems extremely difficult to work with.
      While the ratings provided by the expert evaluators are higher, 0.6 and 0.45,
      respectively, these ratings are still low indicating that they also experienced
      considerable struggles. DISCUSSION: The results of the Track 3 evaluation show
      that the adoptability of the five participating clinical NLP systems has a great
      margin for improvement. Remedy strategies suggested by the evaluators included
      (1) more detailed and operation system specific use instructions; (2) provision
      of more pertinent onscreen feedback for easier diagnosis of problems; (3)
      including screen walk-throughs in use instructions so users know what to expect
      and what might have gone wrong; (4) avoiding jargon and acronyms in materials
      intended for end users; and (5) packaging prerequisites required within software
      distributions so that prospective adopters of the software do not have to obtain
      each of the third-party components on their own.

PMID- 26210362
TI  - Identifying risk factors for heart disease over time: Overview of 2014
      i2b2/UTHealth shared task Track 2.
AB  - The second track of the 2014 i2b2/UTHealth natural language processing shared
      task focused on identifying medical risk factors related to Coronary Artery
      Disease (CAD) in the narratives of longitudinal medical records of diabetic
      patients. The risk factors included hypertension, hyperlipidemia, obesity,
      smoking status, and family history, as well as diabetes and CAD, and indicators
      that suggest the presence of those diseases. In addition to identifying the risk
      factors, this track of the 2014 i2b2/UTHealth shared task studied the presence
      and progression of the risk factors in longitudinal medical records. Twenty teams
      participated in this track, and submitted 49 system runs for evaluation. Six of
      the top 10 teams achieved F1 scores over 0.90, and all 10 scored over 0.87. The
      most successful system used a combination of additional annotations, external
      lexicons, hand-written rules and Support Vector Machines. The results of this
      track indicate that identification of risk factors and their progression over
      time is well within the reach of automated systems. 

PMID- 26210363
TI  - Using Linked Data for polarity classification of patients' experiences.
AB  - Polarity classification is the main subtask of sentiment analysis and opinion
      mining, well-known problems in natural language processing that have attracted
      increasing attention in recent years. Existing approaches mainly rely on the
      subjective part of text in which sentiment is expressed explicitly through
      specific words, called sentiment words. These approaches, however, are still far
      from being good in the polarity classification of patients' experiences since
      they are often expressed without any explicit expression of sentiment, but an
      undesirable or desirable effect of the experience implicitly indicates a positive
      or negative sentiment. This paper presents a method for polarity classification
      of patients' experiences of drugs using domain knowledge. We first build a
      knowledge base of polar facts about drugs, called FactNet, using extracted
      patterns from Linked Data sources and relation extraction techniques. Then, we
      extract generalized semantic patterns of polar facts and organize them into a
      hierarchy in order to overcome the missing knowledge issue. Finally, we apply the
      extracted knowledge, i.e., polar fact instances and generalized patterns, for the
      polarity classification task. Different from previous approaches for personal
      experience classification, the proposed method explores the potential benefits of
      polar facts in domain knowledge aiming to improve the polarity classification
      performance, especially in the case of indirect implicit experiences, i.e.,
      experiences which express the effect of one entity on other ones without any
      sentiment words. Using our approach, we have extracted 9703 triplets of polar
      facts at a precision of 92.26 percent. In addition, experiments on drug reviews
      demonstrate that our approach can achieve 79.78 percent precision in polarity
      classification task, and outperforms the state-of-the-art sentiment analysis and
      opinion mining methods. 

PMID- 26210364
TI  - [Completely free].

PMID- 26210365
TI  - [Dentistry in the Middle Ages in the low lands 6. "Van enen ontbonden tant ende
      van die vuyle verve der tanden"].

PMID- 26210366
TI  - [Cow's milk allergy].
AB  - Cow's milk allergy is the most common food allergy among children. Patients with
      cow's milk allergy may present a wide range of complaints. Complaints can occur
      in multiple organ systems. The gold standard to confirm a diagnosis of cow's milk
      allergy is the double-blind placebo-controlled food challenge. The treatment
      consists of the elimination of cow's milk from a child's diet.It is estimated
      that at the age of 1 year, 75% of children with cow's milkallergy have become
      tolerant to cow's milk, and 90% at the age of 4 years. It is recommended to
      expose all infants with cow's milk allergy to cow's milk at the age of 1 year to
      see if they have become tolerant. 

PMID- 26210367
TI  - [Dissertation 25 years after date 39. Oral self-care by dentate elderly].
AB  - In 1989, the dissertation 'Oral self-care for dentate elderly' was published.
      Among other things, the effect of an information leaflet on oral self-care was
      investigated in a randomised, controlled trial. The outcome of the entire
      intervention was positive. Subsequent to this dissertation no comparable research
      has been carried out in the Netherlands or abroad. Nevertheless, concerns remain
      about the oral self-care of dentate older people. To improve the oral (self-)care
      of nursing home residents, carers should be educated theoretically and
      practically, preferably during their professional training. With regard to older
      people living at home, oral healthcare providers should assess whether their oral
      health condition will be stable for the rest of their life, at the latest when
      their general health condition is beginning to deteriorate. Determining factors
      in this regard are a stable dentition that can easily be kept clean, particularly
      when oral implants are present. As soon as older people who are living at home
      become dependent, they will require support. Oral health care providers should,
      then, make sure that their practices physically accessible and should be prepared
      to deliver care at home. 

PMID- 26210368
TI  - [Evidence-based clinical guidelines in dental practice 5. Guidelines:
      professional autonomy and right of self-determination].
AB  - Judges up to and including the Law Lords (Supreme Court) and the Central
      Disciplinary Tribunal for Healthcare in the Netherlands do not consider
      guidelines to be optional. This offers security to patients and dental care
      professionals. But a field of tension can exist between, on the one hand, a
      patient's right of self-determination and the dental care workers professional
      autonomy and, on the other, a guideline. This field of tension can be resolved by
      first limited testing of the acceptability of the goal of care desired by the
      patient, taking into consideration at the same time professional autonomy; and,
      subsequently, by selecting the most effective treatment for achieving this goal
      of care on the basis of 'evidence'. With respect to the current definition of
      guidelines for clinical practice, this means that patients and healthcare workers
      explicitly acknowledge that they have been able to agree on a goal of care that
      deviates from the ideal. In this way, a judicially responsible balance is
      achieved between the right of self-determination and professional autonomy, on
      the one hand, and, on the other, the desire for evidence-based treatment and a
      limitation on unaccountable variation in treatment and transparency of care. 

PMID- 26210369
TI  - [The extra value of training dental students in surgical skills].
AB  - In 2010, the revised 3-year master's programme was introduced in the Netherlands,
      which meant that the full programme of dental education was extended to 6 years.
      In Nijmegen, this was structured to include a set of profile programmes, next to
      the existing curriculum. Three profiles were chosen, one of which was the
      Surgical Profile. The aim of this programme was that the more complex procedures
      and the treatment of medically compromised patients would be carried out by those
      students in the 6-year educational programme who participated in the Surgical
      Profile. The experiences of students following this profile were evaluated by
      means of a questionnaire. In a second questionnaire, distributed 1 year after the
      students had graduated, respondents were asked whether they were still making use
      of the skills that they had been taught. The conclusion was that the training of
      master's students in dental surgery results in a high degree of satisfaction. The
      study revealed moreover that 93% of the students who completed the Surgical
      Profile put the skills they had been taught to use during the first year as
      dentists and even wanted to build on that knowledge by means of relevant post
      graduate courses. 

PMID- 26210370
TI  - The effect of aging on gait parameters in able-bodied older subjects: a
      literature review.
AB  - BACKGROUND: Gait disorders are common in the elderly populations, and their
      prevalence increases with age. Abnormal gait has been associated with greater
      risk for adverse outcomes in older adults, such as immobility and falls, which in
      turn lead to loss of functional independence and death. AIM: The purpose of this
      review was to evaluate all of the original papers that measured gait parameters
      in the healthy elderly subjects. METHOD: The search strategy was based on
      Population Intervention Comparison Outcome method. A search was performed in Pub
      Med, Science Direct, Google scholar, ISI web of knowledge databases by using the
      selected keywords. Forty-two articles were selected for final evaluation. The
      procedure using the PRISMA method was followed. RESULTS: Stride lengths of older
      subjects ranged between 135 and 153 cm, and they preferred to walk with a 41 %
      increase in step width compared to young subjects. Cadence was reported to be
      between 103 and 112 steps/min in older adults. They consumed an average of 20-30
      % more metabolic energy than younger subjects. All except one study demonstrated
      that older people have significantly reduced gait symmetry. CONCLUSION: The
      progression toward shorter steps and slower walking and increased step width and
      prolonged double support in older adult, may therefore emerge as a compensatory
      strategy aimed at increasing stability, avoiding falls, or reducing the energetic
      cost of mobility.

PMID- 26210372
TI  - Left renal vein compression as cause for varicocele: prevalence and associated
      findings on contrast-enhanced CT.
AB  - PURPOSE: The purpose of this study is to determine the prevalence of left renal
      vein compression in patients with varicoceles. METHODS: Abdominal and pelvis
      contrast-enhanced CT images from 100 male patients with varicoceles (mean age
      50.6 years) and 100 matched control patients (mean age 49.8 years) were
      retrospectively reviewed. The diameter of the left renal vein was measured as it
      crosses between the aorta and superior mesenteric artery and was classified as
      compressed if there was greater than 50% narrowing. The diameter of the left
      gonadal vein was measured at the origin. Comparison of the prevalence of left
      renal vein compression was made via a Chi-squared test and the gonadal vein
      diameter via a t test. RESULTS: The distribution of varicoceles was 68 on the
      left, 24 bilateral, and 8 on the right. Compression of the left renal vein was
      significantly more common in the left varicocele (78%, 53/68) than in the
      bilateral varicocele (42%, 10/24, p = 0.002), right varicocele (13%, 1/8, p <
      0.001), or control group (10%, 10/100, p < 0.001). In the subgroup analysis, the
      gonadal vein diameter was significantly greater in the left varicocele (mean 5.6
      mm) than in the bilateral varicocele (mean 4.6 mm, p = 0.018), right varicocele
      (mean 3.2 mm, p < 0.001), and control group (mean 3.1 mm, p < 0.001). CONCLUSION:
      Left renal vein compression by the superior mesenteric artery is a major
      contributor to left-sided varicoceles.

PMID- 26210371
TI  - Back pain-related disability and quality of life in patients affected by
      vertebral fractures: data from baseline characteristics of population enrolled in
      Denosumab In Real Practice (DIRP).
AB  - BACKGROUND: Spine fragility fractures lead to a significant acute and/or chronic
      pain and worsening of quality of life. Denosumab is effective in reducing the
      risk of new vertebral fractures, but its effectiveness on pain relief and
      improvement of the quality of life in patients with spine fractures are not well
      known. AIM: The aim of this paper is to describe the baseline demographic and
      clinical characteristics, back pain-related disability and quality of life of the
      Denosumab In Real Practice (DIRP) study population. METHODS: DIRP is a
      multicenter prospective observational study evaluating the effectiveness of
      denosumab in reducing back pain-related disability and Health-Related Quality of
      Life (HRQoL) of women with postmenopausal osteoporosis who had already
      experienced at least one vertebral fragility fracture. Our evaluation protocol
      includes history of fractures, Spine Pain Index (SPI), HRQoL, bone mineral
      density (BMD) and radiological assessment of vertebral fragility fractures.
      RESULTS: Two hundred and twenty-three post-menopausal women, who received a
      prescription for denosumab, were enrolled. The mean SPI score was 58.6 +/- 21.4
      SD, and 187 (83.86%) women experienced a moderate-severe pain. The mean HRQoL
      health state value was 0.54 +/- 0.27 SD using EQ-5D index, whereas the mean
      Physical and Mental Health Composite Scale scores derived from the SF-12 were
      31.06 +/- 7.77 SD and 39.20 +/- 11.03 SD. DISCUSSION AND CONCLUSIONS: Baseline
      characteristics of DIRP study cohort indicate that patients who received a
      prescription of denosumab in Campania region are affected by severe osteoporosis
      with highly prevalent vertebral fractures, disabling back pain and poor health
      related quality of life. This is in contradiction with what it is expected by a
      front-line drug for osteoporosis.

PMID- 26210373
TI  - Cognitive adaptations induced by a multi-language input in early development.
AB  - Children around the world successfully adapt to the specific requirements of
      their physical and social environment, and they readily acquire any language they
      are exposed to. Still, learning simultaneously two languages has been a
      continuous concern of parents, educators and scientists. While the focus has
      shifted from the possible costs to the possible advantages of bilingualism, the
      worries still linger that early bilingualism may cause delays and confusion. Here
      we adopt a less dichotomist view, by asking what specific adaptations might
      result from simultaneously learning two languages. We will discuss findings that
      point to a surprising plasticity of the cognitive system allowing young infants
      to cope with the bilingual input and reaching linguistic milestones at the same
      time as monolinguals. 

PMID- 26210375
TI  - Differential sensitivity in embryonic stages of the zebrafish (Danio rerio): The
      role of toxicokinetics for stage-specific susceptibility for azinphos-methyl
      lethal effects.
AB  - The occasionally observed differential chemical sensitivity in embryonic life
      stages of fish is still poorly understood and could represent an important issue
      for understanding the time course of toxicity and the toxic modes of action of
      chemicals. In this study we analyzed the toxicity of the acetylcholinesterase
      inhibitor azinphos-methyl (APM) in different life-stages of zebrafish embryos. To
      this end, the LC50 of three 48h-exposure windows were determined (12MUM for 0-48,
      no mortality observed for 24-72 and 72-120hpf up to a concentration of 79MUM). We
      hypothesized that the differential sensitivity of the stage-specific embryos may
      be related to differences in uptake of the compound and/or internal
      concentrations. Therefore, internal concentrations were determined using HPLC.
      Similar levels and time courses of internal concentrations for all three exposure
      windows were observed. Bioconcentration amounted to a factor of about 30. Short
      term exposure windows for a concentration 4-fold above the calculated LC50
      (47MUM) identified the period of 0-4hpf as the most sensitive time window for APM
      toxicity. Our results indicate that the differential sensitivity of APM in the
      embryos is not related to differences in internal concentrations but related to a
      stage specific mechanisms of toxicity. 

PMID- 26210374
TI  - MRI and intraoperative pathology to predict nipple-areola complex (NAC)
      involvement in patients undergoing NAC-sparing mastectomy.
AB  - BACKGROUND: Nipple-areola sparing mastectomy (NSM) with immediate implant
      reconstruction is an option for patients with non-locally advanced breast cancer.
      The prediction of occult tumour involvement of the nipple-areola complex (NAC)
      may help select candidates to NSM. PATIENTS AND METHODS: We prospectively
      recorded clinical and pathological data, magnetic resonance imaging (MRI) results
      and intraoperative pathological assessments of the subareolar (SD) and proximal
      nipple ducts (ND) of 112 consecutive breast cancer patients scheduled for NSM.
      All parameters were correlated with final pathological NAC assessment by
      univariate and multivariate analysis. RESULTS: Thirty-one patients (27.7%) had
      tumour involvement of the NAC. At univariate analysis, age (p=0.001), post
      menopausal status (0.003), tumour central location (p=0.03), tumour-NAC distance
      measured by MRI (p=0.000) and intraoperative pathologic assessment (SD+ND)
      (p=0.000) were significantly correlated with NAC involvement. At multivariate
      analysis, only MRI tumour-NAC distance (p=0.008) and menopausal status (p=0.039)
      among all preoperative variables retained statistical significance. The
      sensitivity and specificity of MRI tumour-NAC distance were 32.2% and 88.6% and
      those of intraoperative pathologic assessment were 46.7% and 100%, respectively.
      Sensitivity, specificity and accuracy of the double assessment (MRI plus
      intraoperative pathology) were 50.0%, 96.2% and 84.1%, respectively. CONCLUSION:
      Intraoperative pathologic assessment and tumour-NAC distance measured by MRI are
      the most important predictors of occult NAC involvement in breast cancer
      patients. A negative pathological assessment and a tumour-NAC distance ? 5 mm
      allow optimal discrimination between NAC positive and NAC negative cases and may
      serve as a guide for the optimal planning of oncological and reconstructive
      surgery.

PMID- 26210376
TI  - Predicting resting energy expenditure in young adults.
AB  - PURPOSE: To develop and validate a REE prediction equation for young adults.
      METHODS: Baseline data from two studies were pooled (N=318; women=52%) and
      randomly divided into development (n=159) and validation samples (n=159). REE was
      measured by indirect calorimetry. Stepwise regression was used to develop an
      equation to predict REE (University of Kansas (KU) equation). The KU equation and
      5 additional REE prediction equations used in clinical practice (Mifflin-St.
      Jeor, Harris-Benedict, Owens, Frankenfield (2 equations)) were evaluated in the
      validation sample. RESULTS: There were no significant differences between
      predicted and measured REE using the KU equation for either men or women. The
      Mifflin-St. Jeor equation showed a non-significant mean bias in men; however,
      mean bias was statistically significant in women. The Harris-Benedict equation
      significantly over-predicted REE in both men and women. The Owens equation showed
      a significant mean bias in both men and women. Frankenfield equations #1 and #2
      both significantly over-predicted REE in non-obese men and women. We found no
      significant differences between measured REE and REE predicted by the
      Frankenfield #2 equations in obese men and women. CONCLUSION: The KU equation,
      which uses easily assessed characteristics (age, sex, weight) may offer better
      estimates of REE in young adults compared with the 5 other equations. The KU
      equation demonstrated adequate prediction accuracy, with approximately equal
      rates of over and under-prediction. However, enthusiasm for recommending any REE
      prediction equations evaluated for use in clinical weight management is damped by
      the highly variable individual prediction error evident with all these equations.

PMID- 26210377
TI  - Blood free fatty acids were not increased in high-fat diet induced obese insulin
      resistant animals.
AB  - OBJECTIVE: The close connection between high blood FFA and insulin resistance
      (IR) in obese individuals is well-known. The purpose of this study was to
      identify whether the blood FFA increased in obese-IR animals. METHODS: Obese-IR
      animal models were established using high-fat diet (HFD) or HFD and streptozocin,
      and treated with drugs. RESULTS: The serum FFA of obese-IR animals was not
      increased, even significantly lower than that of normal animals, and were not
      significantly decreased when insulin sensitivity and obesity-related indices were
      ameliorated after treatment. CONCLUSION: The results suggest that blood FFA are
      unlikely the link between obesity and insulin resistance.

PMID- 26210379
TI  - Cost Savings in Trauma Systems: The Devil's in the Details.

PMID- 26210378
TI  - Differential effects of acute administration of SCH-23390, a D1 receptor
      antagonist, and of ethanol on swimming activity, anxiety-related responses, and
      neurochemistry of zebrafish.
AB  - RATIONALE: The zebrafish has become an increasingly popular animal model for
      investigating ethanol's actions in the brain and its effects on behavior. Acute
      exposure to ethanol in zebrafish has been shown to induce a dose-dependent
      increase of locomotor activity, to reduce fear- and anxiety-related behavioral
      responses, and to increase the levels of dopamine and its metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC). OBJECTIVES: The objective of the present
      study was to investigate the role of dopamine D1 receptors (D1-R) in ethanol
      induced locomotor activity in zebrafish. METHODS: Zebrafish were pre-treated with
      SCH-23390 (0 or 1 mg/L bath concentration), a D1-R antagonist, and subsequently
      exposed to ethanol (0, 0.25, 0.5, 1.0 % v/v). To explore potential underlying
      mechanisms, we quantified levels of dopamine, DOPAC, serotonin, and 5-HIAA from
      whole-brain tissue using high-precision liquid chromatography. RESULTS: We found
      pre-treatment with the D1-R antagonist to attenuate locomotor activity
      independent of ethanol concentration. Furthermore, unlike ethanol, D1-R
      antagonism did not alter behavioral responses associated with fear and anxiety.
      Pre-treatment with SCH-23390 decreased levels of dopamine and DOPAC, but this
      effect was also independent of ethanol concentration. The D1-R antagonist also
      reduced serotonin and 5-hydroxyindole acetic acid (5-HIAA) levels. CONCLUSION:
      These results suggest a multifaceted and at least partially independent role of
      dopamine D1 receptors in ethanol-induced locomotor activity and anxiety-related
      responses as well as in the functioning of the dopaminergic and serotoninergic
      neurotransmitter systems in zebrafish.

PMID- 26210380
TI  - Does Ultrasonographic Guidance Reduce Failure Rates and Adverse Events for
      Subclavian Vein Catheterization Compared With the Landmark Technique?

PMID- 26210381
TI  - Can Vasopressors Safely Be Administered Through Peripheral Intravenous Catheters
      Compared With Central Venous Catheters?

PMID- 26210382
TI  - Do Systemic Corticosteroids Improve Outcomes in Chronic Obstructive Pulmonary
      Disease Exacerbations?

PMID- 26210383
TI  - Does Mannitol Reduce Mortality From Traumatic Brain Injury?

PMID- 26210384
TI  - Is there role of additional chemotherapy after definitive local treatment for
      stage I/II marginal zone lymphoma?: Consortium for Improving Survival of Lymphoma
      (CISL) study.
AB  - Even though local stage (Ann Arbor stage I/II) marginal zone lymphoma (MZL) is
      well controlled with local treatment-based therapy, no data exist on the role of
      additional chemotherapy after local treatment for stage I/II MZL. Patients with
      biopsy-confirmed Ann Arbor stage I/II MZL (n = 210) were included for analysis in
      this study. Of these, 180 patients (85.7 %) were stage I and 30 (14.3 %) were
      stage II. Most patients (n = 182, 86.7 %) were treated with a local modality
      including radiation therapy or surgery and 28 (13.3 %) received additional
      systemic chemotherapy after local treatment. The overall response rate was 98.3 %
      (95 % CI 96-100 %), with 187 complete responses and 20 partial responses. In the
      local treatment group, the mean progression-free survival (PFS) was 147.4 months
      (95 % CI 126.7-168.1 months) and the overall survival (OS) was 188.2 months (95 %
      CI 178.8-197.7 months). In the additional chemotherapy group, the mean PFS was
      103.4 months (95 % CI 84.9-121.9 months) and the OS was 137.3 months (95 % CI
      127.9-146.7 months). There was no difference between the two groups in OS (p =
      0.836) and PFS (p = 0.695). Local stage MZL has a good clinical course and is
      well controlled with a local treatment modality without additional chemotherapy.

PMID- 26210385
TI  - Molecular studies on ancient M. tuberculosis and M. leprae: methods of pathogen
      and host DNA analysis.
AB  - Humans have evolved alongside infectious diseases for millennia. Despite the
      efforts to reduce their incidence, infectious diseases still pose a tremendous
      threat to the world population. Fast development of molecular techniques and
      increasing risk of new epidemics have resulted in several studies that look to
      the past in order to investigate the origin and evolution of infectious diseases.
      Tuberculosis and leprosy have become frequent targets of such studies, owing to
      the persistence of their molecular biomarkers in ancient material and the
      characteristic skeletal lesions each disease may cause. This review examines the
      molecular methods used to screen for the presence of M. tuberculosis and M.
      leprae ancient DNA (aDNA) and their differentiation in ancient human remains.
      Examples of recent studies, mainly from Europe, that employ the newest techniques
      of molecular analysis are also described. Moreover, we present a specific
      approach based on assessing the likely immunological profile of historic
      populations, in order to further elucidate the influence of M. tuberculosis and
      M. leprae on historical human populations. 

PMID- 26210386
TI  - Dramatic decrease of Streptococcus pneumoniae infections in Marseille, 2003-2014.
AB  - We studied the evolution of the prevalence of pneumococcal infections in
      university hospitals in Marseille, France, from January 2003 to December 2014,
      and compared our observations and results to available international data. We
      collected data referring to patients hospitalised for Streptococcus pneumoniae
      infections in the four university hospitals of Marseille from January 2003 to
      December 2014. We then calculated percentages of positiveness to pneumococcal
      strains by dividing the annual number of patients infected by pneumococcal
      strains by the annual number of patients found to be infected by at least one
      bacterial species in the settings of interest throughout the study period.
      Overall, 2442 non-redundant patients were infected by S. pneumoniae strains
      throughout the study period. We observed that the annual percentage of patients
      infected by S. pneumoniae significantly decreased throughout the study period
      (from 1.99% in 2003 to 0.77% in 2014, p-value < 10(-4)). A significant
      correlation was obtained comparing the annual evolution of the percentage of
      patients positive to pneumococcal strains aged under 21 years to that of patients
      aged over 21 years (r = 0.93, p-value < 10(-5)). Our results allowed us to prove
      that national immunisation programmes effectively impact on the pneumococcal
      infection prevalence in young and elderly populations, even on the regional
      scale.

PMID- 26210387
TI  - Clinical and antimicrobial efficacy of a controlled-release device containing
      chlorhexidine in the treatment of chronic periodontitis.
AB  - A controlled-release device (CRD) containing chlorhexidine gluconate, such as
      PerioCol(TM)CG (Eucare Pharmaceuticals Pvt. Ltd,, Chennai, India), for
      subgingival application has little reported data with clinical as well as
      antimicrobial efficacy. This study evaluated clinical and subgingival microbial
      changes on using indigenously developed PerioColTMCG as an adjunct to scaling and
      root planing (SRP) in the treatment of chronic periodontitis. Forty posterior
      first molar sites having probing pocket depth >= 5 mm were selected and divided
      into two groups, with 20 sites in each group, in a split-mouth design. Group A
      (test site) was treated with SRP and PerioCol(TM)CG, while group B (control site)
      was treated with SRP alone. Subgingival microbial samples were collected at
      baseline and 1 month after the initial SRP, while probing depth (PD), clinical
      attachment level (CAL) and gingival index (GI) were recorded at baseline, after 1
      month and after 3 months. Microbial detection of Porphyromonas gingivalis (P.
      gingivalis) and Tannerella forsythia (T. forsythia) was done by means of
      polymerase chain reaction (PCR). A significant improvement was observed in all
      clinical measures in sites treated with PerioCol(TM)CG as compared to the control
      sites during the study period. Also, there was a statistically significant
      reduction in the proportion of occurrence of P. gingivalis and T. forsythia after
      intervention in test sites as compared to control sites. Our data suggest that
      SRP combined with subgingival administration of PerioColTMCG has a significantly
      better and prolonged effect compared to SRP alone on the PD, clinical attachment
      loss and elimination of periodontopathogens.

PMID- 26210388
TI  - Metabolic characteristics of youth with loss of control eating.
AB  - PURPOSE: Preliminary data in adults suggest that binge eating is associated with
      greater prevalence of metabolic syndrome (MetS) components. However, there are
      limited data in youth, and little is known of the role of binge episode size in
      these relationships. METHODS: We examined the relationship between loss of
      control eating and metabolic characteristics in a convenience sample of 329
      treatment-seeking and non-treatment-seeking adolescent boys and girls. The sample
      was enriched by design with adolescents who were overweight or obese and with
      individuals who reported episodes of loss of control over their eating (either
      objectively large binge episodes, OBEs or subjectively large binge episodes,
      SBEs, in the past month), as assessed by clinical interview. MetS components
      (blood pressure, lipids, glucose, and waist circumference) were the primary
      variables of interest. RESULTS: 46% of the cohort reported loss of control
      eating; among those, 53% reported SBEs only and 47% reported OBEs. Youth with
      loss of control eating had higher systolic blood pressure (p=.001) and higher low
      density lipoprotein cholesterol (LDL-c) (p=.002) compared to those without loss
      of control eating, in analyses adjusted for intervention-seeking status, fat mass
      and sociodemographic characteristics. Youth reporting OBEs had higher LDL-c
      (p=.013) compared to those reporting only SBEs. CONCLUSIONS: Adolescents
      reporting loss of control episodes had greater dysfunction in some components of
      the MetS compared to youth without loss of control; episode size may contribute
      to metabolic dysfunction.

PMID- 26210389
TI  - The general radiologist's role in breast cancer risk assessment: breast density
      measurement on chest CT.
AB  - To determine if general radiologists can accurately measure breast density on low
      dose chest computed tomographic (CT) scans, two board-certified radiologists with
      expertise in mammography and CT scan interpretation, and seven general
      radiologists performed retrospective review of 100 women's low-dose chest CT
      scans. CT breast density grade based on Breast Imaging Reporting and Data System
      grades was independently assigned for each case. Kappa statistic was used to
      compare agreement between the expert consensus grading and those of the general
      radiologists. Kappa statistics were 0.61-0.88 for the seven radiologists, showing
      substantial to excellent agreement and leading to the conclusion that general
      radiologists can be trained to determine breast density on chest CT. 

PMID- 26210390
TI  - Alcohol binding in the C1 (C1A+C1B) domain of protein kinase C epsilon.
AB  - BACKGROUND: Alcohol regulates the expression and function of protein kinase C
      epsilon (PKCepsilon). In a previous study we identified an alcohol binding site
      in the C1B, one of the twin C1 subdomains of PKCepsilon (Das et al., Biochem. J.,
      421, 405-13, 2009). METHODS: In this study, we investigated alcohol binding in
      the entire C1 domain (combined C1A and C1B) of PKCepsilon. Fluorescent phorbol
      ester, SAPD and fluorescent diacylglycerol (DAG) analog, dansyl-DAG were used to
      study the effect of ethanol, butanol, and octanol on the ligand binding using
      fluorescence resonance energy transfer (FRET). To identify alcohol binding
      site(s), PKCepsilonC1 was photolabeled with 3-azibutanol and 3-azioctanol, and
      analyzed by mass spectrometry. The effects of alcohols and the azialcohols on
      PKCepsilon were studied in NG108-15 cells. RESULTS: In the presence of alcohol,
      SAPD and dansyl-DAG showed different extent of FRET, indicating differential
      effects of alcohol on the C1A and C1B subdomains. Effects of alcohols and
      azialcohols on PKCepsilon in NG108-15 cells were comparable. Azialcohols labeled
      Tyr-176 of C1A and Tyr-250 of C1B. Inspection of the model structure of
      PKCepsilonC1 reveals that these residues are 40A apart from each other indicating
      that these residues form two different alcohol binding sites. CONCLUSIONS: The
      present results provide evidence for the presence of multiple alcohol-binding
      sites on PKCepsilon and underscore the importance of targeting this PKC isoform
      in developing alcohol antagonists.

PMID- 26210391
TI  - Hypertension in patients with Alzheimer's disease--prevalence, characteristics,
      and impact on clinical outcome. Experience of one neurology center in Poland.
AB  - The aim of the study was to evaluate hypertension (HT) prevalence,
      characteristics, and impact on clinical outcome in patients with Alzheimer's
      disease (AD). We evaluated 701 patients with AD (249 males, 452 females, and mean
      age 74.9 +/- 7.5 years). As a group representing general population matched with
      regard to age, education level, and place of residence, we included 762 subjects
      (438 males, 324 females, and mean age 74.7 +/- 4.4 years) from the Polish
      National Multicenter Health Survey (WOBASZ) studies. The patients with AD were
      characterized by lower systolic blood pressure (BP) and diastolic BP values (134
      +/- 21 vs. 151 +/- 23 mm Hg, P < .001 and 77 +/- 11 vs. 86 +/- 12 mm Hg, P <
      .001, respectively) as well as lower HT prevalence (66% vs. 78.6%, P < .001)
      compared with the WOBASZ group. In long-term follow-up of AD group, HT and BP
      levels were not associated with the decline in cognitive functions nor the
      increased risk of death. Patients with AD were characterized by lower prevalence
      of HT and other vascular risk factors. BP levels and HT had no impact on clinical
      outcome. 

PMID- 26210392
TI  - Do hypnotic drugs cause cancer, like cigarettes?

PMID- 26210393
TI  - The opium poppy as a symbol of sleep in Bertel Thorvaldsen's relief of 1815.
AB  - Danish sculptor Bertel Thorvaldsen (1770-1844) is one of the most remarkable
      representatives of Neoclassicist sculptural art in Europe, which was largely
      inspired by the classical art and culture of Greek and Roman antiquity. A pair of
      marble reliefs, Night and Day, exhibited in the Thorvaldsen Museum (Copenhagen),
      marks the culmination of Thorvaldsen's relief art and is of particular interest
      to the history of sleep medicine. In the first relief, Night, an angel with her
      neck bent and eyes closed has two babies in her embrace and seems to be floating
      down in grief, with an owl hovering behind her. Her hair is also twined with
      opium poppies, the symbol of sleep and death in antiquity. Our findings suggest
      that this relief not only indicates a mythological association between the opium
      poppy and sleep but also has a strong connotation with the poppy's medicinal use
      for inducing sleep throughout the centuries.

PMID- 26210394
TI  - Response to the letter "Potential role for drug induced sleep endoscopy (DISE) in
      pediatric OSA".

PMID- 26210395
TI  - MATPLM1, A MATLAB script for scoring of periodic limb movements: preliminary
      validation with visual scoring.
AB  - BACKGROUND AND PURPOSE: A Matrix Laboratory (MATLAB) script (MATPLM1) was
      developed to rigorously apply World Associations of Sleep Medicine (WASM) scoring
      criteria for periodic limb movements in sleep (PLMS) from bilateral
      electromyographic (EMG) leg recordings. This study compares MATPLM1 with both
      standard technician and expert detailed visual PLMS scoring. METHODS AND
      SUBJECTS: Validation was based on a 'macro' level by agreement for PLMS/h during
      a night recording and on a 'micro' level by agreement for the detection of each
      PLMS from a stratified random sample for each subject. Data available for these
      analyses were from 15 restless leg syndrome (RLS) (age: 61.5 +/- 8.5, 60% female)
      and nine control subjects (age: 61.4 +/- 7.1, 67% female) participating in
      another study. RESULTS: In the 'micro' analysis, MATPLM1 and the visual detection
      of PLMS events agreed 87.7% for technician scoring and 94.4% for expert scoring.
      The technician and MATPLM1 scoring disagreements were checked for 36 randomly
      selected events, 97% involved clear technician-scoring error. In the 'macro'
      analysis, MATPLM1 rates of PMLS/h correlated highly with visual scoring by the
      technician (r(2) = 0.97) and the expert scorer (r(2) = 0.99), but the technician
      scoring was consistently less than MATPLM1: median (quartiles) difference: 10 (5,
      23). There was little disagreement with expert scorer [median (quartile)
      difference: -0.3 (-2.4, 0.3)]. CONCLUSIONS: The MATPLM1 produces reliable scoring
      of PLMS that matches expert scoring. The standard visual scoring without careful
      measuring of events tends to significantly underscore PLMS. These preliminary
      results support the use of MATPLM1 as a preferred method of scoring PLMS for EMG
      recordings that are of a good quality and without significant sleep-disordered
      breathing events.

PMID- 26210396
TI  - Ovarian activity and estrus behavior in early postpartum cows grazing Leucaena
      leucocephala in the tropics.
AB  - The legume Leucaena leucocephala (Leucaena) is widely used to supplement forage
      in silvopastoral livestock systems in Latin America. Little is known about its
      possible effects on the cow reproductive dynamic. The aim was to evaluate the
      effect of Leucaena foliage intake on re-establishment of ovarian activity and
      estrus behavior in early postpartum (7-90 days) cows. Twenty-four multiparous Bos
      taurus * Bos indicus cows were divided into two homogenous groups and assigned to
      one of two treatments: a silvopastoral system (SS, n = 12), consisting of an
      association of Cynodon nlemfuensis grass and L. leucocephala; and a control
      system (CS, n = 12), consisting of C. nlemfuensis alone. Intake of Leucaena in
      the SS ranged from 3.80 to 6.43 kg DM/cow/day. Plasma mimosine concentrations
      ranged from 1270 to 1530 MUg/mL, and those for 2,3-dihydroxypyridine (DHP) from
      147 to 729 MUg/mL. No 3,4-DHP was detected in plasma. No difference (P > 0.05)
      between treatments was observed for the number of cows exhibiting small, medium,
      or dominant follicles, or estrus behavior. The number of cows which re
      established ovarian cyclicity (n = 6) was lower (P < 0.05) in the SS than in the
      CS (n = 9). Corpus luteum lifespan was longer (P < 0.05) in the SS than in the
      CS. Intake of Leucaena affected the number of cows exhibiting ovarian cyclicity
      and extended corpus luteum life, but did not affect follicular development and
      estrus behavior. 

PMID- 26210397
TI  - Taenia hydatigena cysticercosis in slaughtered pigs, goats, and sheep in
      Tanzania.
AB  - Few studies have been carried out in Africa to estimate the prevalence of Taenia
      hydatigena. With the aim to determine the prevalence of T. hydatigena in
      slaughtered pigs and small ruminants (goats and sheep) in Mbeya, Tanzania, two
      cross-sectional surveys were carried out investigating pigs in April to May 2014
      and small ruminants in September 2012. In total, 243 pigs were examined post
      mortem for T. hydatigena cysts which were found in 16 (6.6 %) pigs. The majority
      (80 %) of cysts were found on the omentum and the rest on the liver (20 %), all
      on the visceral surface. Two pigs were also found infected with Taenia solium but
      showed no signs of other infections. A total of 392 goats and 27 sheep were
      examined post-mortem, and the prevalence of T. hydatigena was similar in goats
      and sheep with 45.7 and 51.9 %, respectively. DNA sequencing of the mitochondrial
      cytochrome c oxidase subunit 1 gene (cox1) from a subsample of metacestodes from
      goats and sheep confirmed the T. hydatigena infection. The prevalence found in
      small ruminants was comparable to other studies conducted in Africa, but for
      pigs, it is one of the highest recorded to date. The present study also confirms
      the occurrence of T. hydatigena and T. solium in pigs from Mbeya. Further studies
      are needed to determine the impact of T. hydatigena on production under sub
      Saharan conditions and the financial consequences for smallholder farmers. 

PMID- 26210398
TI  - FRET-based Molecular Tension Microscopy.
AB  - Cells generate and experience mechanical forces that may shape tissues and
      regulate signaling pathways in a variety of physiological or pathological
      situations. How forces propagate and transduce signals at the molecular level is
      poorly understood. The advent of FRET-based Molecular Tension Microscopy now
      allows to achieve mechanical force measurements at a molecular scale with
      molecular specificity in situ, and thereby better understand the mechanical
      architecture of cells and tissues, and mechanotransduction pathways. In this
      review, we will first expose the basic principles of FRET-based MTM and its
      various incarnations. We will describe different ways of measuring FRET, their
      advantages and drawbacks. Then, throughout the range of proteins of interest,
      cells and organisms to which it has been applied, we will review the tests
      developed to validate the approach, how molecular tension was related to cell
      functions, and conclude with possible developments and offshoots. 

PMID- 26210399
TI  - Identification, validation, and characterization of noncanonical miRNAs.
AB  - Many eukaryotes and some viruses encode microRNAs (miRNAs), small RNAs that post
      transcriptionally regulate gene expression. While most miRNAs are generated
      through the activity of RNA Polymerase II (RNAP II) and subsequent processing by
      Drosha and Dicer, some viral miRNAs utilize alternative pathways of biogenesis.
      Some members of the herpesvirus and retrovirus families can direct synthesis of
      miRNAs through RNAP III transcription rather than RNAP II and can utilize
      atypical enzymes to generate miRNAs. Though the advantages of alternative miRNA
      biogenesis remain unclear for herpesviruses, the retroviral miRNA biogenesis
      routes allow the RNAP II transcribed retroviral genome to escape Drosha cleavage
      while still expressing abundant, biologically-active miRNAs. These RNAP III
      derived miRNAs have unique characteristics that allow for their identification
      and characterization. In this article, we describe procedures to predict,
      validate, and characterize RNAP III-transcribed miRNAs and other small RNAs,
      while providing resources that are also useful for canonical miRNAs.

PMID- 26210400
TI  - Construction of an instant structured illumination microscope.
AB  - A challenge in biological imaging is to capture high-resolution images at fast
      frame rates in live cells. The "instant structured illumination microscope"
      (iSIM) is a system designed for this purpose. Similarly to standard structured
      illumination microscopy (SIM), an iSIM provides a twofold improvement over
      widefield microscopy, in x, y and z, but also allows much faster image
      acquisition, with real-time display of super-resolution images. The assembly of
      an iSIM is reasonably complex, involving the combination and alignment of many
      optical components, including three micro-optics arrays (two lenslet arrays and
      an array of pinholes, all with a pitch of 222 MUm) and a double-sided scanning
      mirror. In addition, a number of electronic components must be correctly
      controlled. Construction of the system is therefore not trivial, but is highly
      desirable, particularly for live-cell imaging. We report, and provide
      instructions for, the construction of an iSIM, including minor modifications to a
      previous design in both hardware and software. The final instrument allows us to
      rapidly acquire fluorescence images at rates faster than 100 fps, with
      approximately twofold improvement in resolution in both x-y and z; sub
      diffractive biological features have an apparent size (full width at half
      maximum) of 145 nm (lateral) and 320 nm (axial), using a 1.49 NA objective and
      488 nm excitation.

PMID- 26210401
TI  - Design and construction of conformational biosensors to monitor ion channel
      activation: A prototype FlAsH/BRET-approach to Kir3 channels.
AB  - Ion channels play a vital role in numerous physiological functions and drugs that
      target them are actively pursued for development of novel therapeutic agents.
      Here we report a means for monitoring in real time the conformational changes
      undergone by channel proteins upon exposure to pharmacological stimuli. The
      approach relies on tracking structural rearrangements by monitoring changes in
      bioluminescence energy transfer (BRET). To provide proof of principle we have
      worked with Kir3 neuronal channels producing 10 different constructs which were
      combined into 17 donor-acceptor BRET pairs. Among these combinations, pairs
      bearing the donor Nano-Luc (NLuc) at the C-terminal end of Kir3.2 subunits and
      the FlAsH acceptor at the N-terminal end (NT) or the interfacial helix (N70) of
      Kir3.1 subunits were identified as potential tools. These pairs displayed
      significant changes in energy transfer upon activation with direct channel
      ligands or via stimulation of G protein-coupled receptors. Conformational changes
      associated with channel activation followed similar kinetics as channel currents.
      Dose response curves generated by different agonists in FlAsH-BRET assays
      displayed similar rank order of potency as those obtained with conventional BRET
      readouts of G protein activation and ion flux assays. Conformational biosensors
      as the ones reported herein should prove a valuable complement to other
      methodologies currently used in channel drug discovery. 

PMID- 26210402
TI  - Effect of an osmotic stress on multicellular aggregates.
AB  - There is increasing evidence that multicellular structures respond to mechanical
      cues, such as the confinement and compression exerted by the surrounding
      environment. In order to understand the response of tissues to stress, we
      investigate the effect of an isotropic stress on different biological systems.
      The stress is generated using the osmotic pressure induced by a biocompatible
      polymer. We compare the response of multicellular spheroids, individual cells and
      matrigel to the same osmotic perturbation. Our findings indicate that the osmotic
      pressure occasioned by polymers acts on these systems like an isotropic
      mechanical stress. When submitted to this pressure, the volume of multicellular
      spheroids decreases much more than one could expect from the behavior of
      individual cells. 

PMID- 26210403
TI  - Histone profiles in cancer.
AB  - While DNA abnormalities have long been recognized as the cause of cancer, the
      contribution of chromatin is a relatively recent discovery. Excitement in the
      field of cancer epigenetics is driven by 3 key elements: 1. Chromatin may play an
      active and often critical role in controlling gene expression, DNA stability and
      cell identity. 2. Chromatin modifiers are frequent targets of DNA aberrations, in
      some cancers reaching near 100%. Particularly in cancers with low rates of DNA
      mutations, the key "driver" of malignancy is often a chromatin modifier. 3.
      Cancer-associated aberrant chromatin is amenable to pharmacologic modulation.
      This has sparked the rapidly expanding development of small molecules targeting
      chromatin modifiers or reader domains, several of which have shown promise in
      clinical trials. In parallel, technical advances have greatly enhanced our
      ability to perform comprehensive chromatin/histone profiling. Despite the
      discovery that distinct histone profiles are associated with prognostic
      subgroups, and in some instances may point towards an underlying aberration that
      can be targeted, histone profiling has not entered clinical diagnostics. Even
      eligibility for clinical trials targeting chromatin hinges on traditional
      histologic or DNA-based molecular criteria rather than chromatin profiles. This
      review will give an overview of the philosophical debate around the role of
      histones in controlling or modulating gene expression and discuss the most common
      techniques for histone profiling. In addition, we will provide prominent examples
      of aberrantly expressed or mutated chromatin modifiers that result in either
      globally or locally aberrant histone profiles, and that may be promising
      therapeutic targets. 

PMID- 26210404
TI  - Cell-penetrating peptides transport therapeutics into cells.
AB  - Nearly 30years ago, certain small, relatively nontoxic peptides were discovered
      to be capable of traversing the cell membrane. These cell-penetrating peptides,
      as they are now called, have been shown to not only be capable of crossing the
      cell membrane themselves but can also carry many different therapeutic agents
      into cells, including small molecules, plasmid DNA, siRNA, therapeutic proteins,
      viruses, imaging agents, and other various nanoparticles. Many cell-penetrating
      peptides have been derived from natural proteins, but several other cell
      penetrating peptides have been developed that are either chimeric or completely
      synthetic. How cell-penetrating peptides are internalized into cells has been a
      topic of debate, with some peptides seemingly entering cells through an endocytic
      mechanism and others by directly penetrating the cell membrane. Although the
      entry mechanism is still not entirely understood, it seems to be dependent on the
      peptide type, the peptide concentration, the cargo the peptide transports, and
      the cell type tested. With new intracellular disease targets being discovered,
      cell-penetrating peptides offer an exciting approach for delivering drugs to
      these intracellular targets. There are hundreds of cell-penetrating peptides
      being studied for drug delivery, and ongoing studies are demonstrating their
      success both in vitro and in vivo. 

PMID- 26210405
TI  - Comparison of marine sampling methods for organic contaminants: Passive samplers,
      water extractions, and live oyster deployment.
AB  - Laboratory and field trials evaluated the efficacy of three methods of detecting
      aquatic pesticide concentrations. Currently used pesticides: atrazine,
      metolachlor, and diazinon and legacy pesticide dieldrin were targeted. Pesticides
      were extracted using solid-phase extraction (SPE) of water samples, titanium
      plate passive samplers coated in ethylene vinyl acetate (EVA) and eastern oysters
      (Crassostrea viginica) as biosamplers. A laboratory study assessed the extraction
      efficiencies and precision of each method. Passive samplers yielded the highest
      precision of the three methods (RSD: 3-14% EVA plates; 19-60% oysters; and 25-56%
      water samples). Equilibrium partition coefficients were derived. A significant
      relationship was found between the concentration in oyster tissue and the ambient
      aquatic concentration. In the field (Housatonic River, CT (U.S.)) water sampling
      (n = 5) detected atrazine at 1.61-7.31 MUg L(-1), oyster sampling (n = 2*15)
      detected dieldrin at n.d.-0.096 MUg L(-1) SW and the passive samplers (n = 5*3)
      detected atrazine at 0.97-3.78 MUg L(-1) SW and dieldrin at n.d.-0.68 MUg L(-1)
      SW. 

PMID- 26210406
TI  - Anti-predatory responses of the thick shell mussel Mytilus coruscus exposed to
      seawater acidification and hypoxia.
AB  - Ocean acidification and hypoxia, both caused by anthropogenic activities, have
      showed deleterious impacts on marine animals. However, their combined effect on
      the mussel's defence to its predator has been poorly understood, which hinders us
      to understand the prey-predator interaction in marine environment. The thick
      shell mussel Mytilus coruscus and its predator, the Asian paddle crab Charybdis
      japonica were exposed to three pH levels (7.3, 7.7, 8.1) at two concentrations of
      dissolved oxygen (2.0 mg L(-1), 6.0 mg L(-1)) seawater. The anti-predatory
      responses of mussels, in terms of byssus thread production were analyzed after 72
      h exposure. During the experiment, frequency of shedding stalks (mussels shed
      their byssal stalks to release themselves from attachment and allow locomotion)
      and number of byssus threads increased with time, were significantly reduced by
      hypoxia and low pH levels, and some interactions among time, predator, DO and pH
      were observed. As expected, the presence of the crab induced an anti-predator
      response in M. coruscus (significant increases in most tested parameters except
      the byssus thread length). Acidification and hypoxia significantly reduced byssus
      thread diamter at the end of the experiment, but not the byssus thread length.
      Cumulative byssus thread length and volume were significantly impaired by hypoxia
      and acidification. Our results highlight the significance of anti-predatory
      responses for adult mussel M. coruscus even under a stressful environment in
      which stress occurs through ocean acidification and hypoxia. By decreasing the
      strength of byssus attachment, the chance of being dislodged and consumed by
      crabs is likely increased. Our data suggest that there are changes in byssus
      production induced by hypoxia and acidification, which may affect predation rates
      on M. coruscus in the field. 

PMID- 26210407
TI  - Patterns of seasonal variation in lagoonal macrozoobenthic assemblages (Mellah
      lagoon, Algeria).
AB  - In coastal lagoons, many studies indicated that macrozoobenthic assemblages
      undergo marked temporal fluctuations as related to the strong environmental
      variability of these systems. However, most of these studies have not assessed
      the seasonal patterns of these fluctuations and none of them has investigated the
      consistency of this variation in different areas within the same lagoon system.
      In this study, we assessed patterns of variation at multiple temporal (date,
      season and year) scales in two different areas in the coastal lagoon of Mellah
      (northeast Algeria). These areas (hereafter Shore and Center) are representative
      of two different environments typically found in coastal lagoons. The Shore
      (water depth of about 1.5-2 m) is characterized by relatively higher
      hydrodynamics, sand to silty-sand sediments and the presence of vegetation
      (Ruppia maritima), the Center (water depth of about 3-3.5 m) is characterized by
      mud to sandy-mud, organic-enriched sediments due to fine particle accumulation.
      Results showed two distinct patterns of seasonal variation in Shore and Center
      assemblages for two consecutive years. In Shore, species richness (S), total
      abundance (N) and the abundance of several dominant taxa were highest in summer
      and/or autumn. This pattern can be related to the local environmental conditions
      maintaining relatively well oxidized conditions, while increasing food
      availability, and favoring the recruitment of species and individuals in
      summer/autumn. On the contrary in Center, S was lowest in summer and autumn, and
      N and the abundance of fewer dominant taxa were lowest in summer. In Center, the
      bivalve Loripes lucinalis showed a 10-fold increase from summer to autumn in both
      years, likely related to the lagoon's hydrodynamics favoring larval transport and
      settlement in the central sector of the lagoon. Overall, the seasonal variation
      found in Center followed a regression/recovery pattern typical of opportunistic
      assemblages occurring in confined organic-enriched environments. In conclusion,
      our results provide new insight into the patterns of seasonal variation in lagoon
      soft-sediment benthos and highlight the importance of local environmental
      conditions on this variation. This study provides a valuable tool for adopting
      appropriate monitoring strategies in these systems, with special reference to
      Southern-Eastern Mediterranean lagoons which are expected to suffer from
      increasing coastal development and human pressure in the near future. 

PMID- 26210408
TI  - Evaluation of low copper content antifouling paints containing natural phenolic
      compounds as bioactive additives.
AB  - Cuprous oxide is the most commonly used biocide in antifouling paints. However,
      copper has harmful effects not only on the fouling community but also on non
      target species. In the current study, we investigated the use of thymol, eugenol
      and guaiacol in this role combined with small quantities of copper. Phenolic
      compounds were tested for anti-settlement activity against cyprid larvae of the
      barnacle Balanus amphitrite and for their toxicity to nauplius larvae. Thymol,
      eugenol and guaiacol were active for anti-settlement but guaiacol had the
      disadvantage of being toxic to nauplius larvae. However, all of them showed
      therapeutic ratio>1. Antifouling paints with thymol (low copper content/thymol,
      LCP/T), eugenol (low copper content/eugenol, LCP/E) and guaiacol (low copper
      content/guaiacol, LCP/G) combined with small copper content were formulated for
      field trials. After 12 months exposure in the sea, statistical analysis revealed
      that LCP/T and LCP/E paints were the most effective combinations and had similar
      performances to control paints with high copper content (traditional cuprous
      oxide based paints). In contrast, LCP/G paint was only partially effective in
      preventing and inhibiting biofouling and was colonized by some hard and soft
      foulers. However, this antifouling paint was effective against calcareous
      tubeworm Hydroides elegans. In the light of various potential applications,
      thymol, eugenol and guaiacol have thus to be considered in future antifouling
      formulations. 

PMID- 26210409
TI  - Selvester scoring in patients with strict LBBB using the QUARESS software.
AB  - BACKGROUND: Estimation of the infarct size from body-surface ECGs in post
      myocardial infarction patients has become possible using the Selvester scoring
      method. Automation of this scoring has been proposed in order to speed-up the
      measurement of the score and improving the inter-observer variability in
      computing a score that requires strong expertise in electrocardiography. In this
      work, we evaluated the quality of the QuAReSS software for delivering correct
      Selvester scoring in a set of standard 12-lead ECGs. METHOD: Standard 12-lead
      ECGs were recorded in 105 post-MI patients prescribed implantation of an
      implantable cardiodefibrillator (ICD). Amongst the 105 patients with standard
      clinical left bundle branch block (LBBB) patterns, 67 had a LBBB pattern meeting
      the strict criteria. The QuAReSS software was applied to these 67 tracings by two
      independent groups of cardiologists (from a clinical group and an ECG core
      laboratory) to measure the Selvester score semi-automatically. Using various
      level of agreement metrics, we compared the scores between groups and when
      automatically measured by the software. RESULTS: The average of the absolute
      difference in Selvester scores measured by the two independent groups was 1.4+/
      1.5 score points, whereas the difference between automatic method and the two
      manual adjudications were 1.2+/-1.2 and 1.3+/-1.2 points. Eighty-two percent
      score agreement was observed between the two independent measurements when the
      difference of score was within two point ranges, while 90% and 84% score
      agreements were reached using the automatic method compared to the two manual
      adjudications. CONCLUSION: The study confirms that the QuAReSS software provides
      valid measurements of the Selvester score in patients with strict LBBB with
      minimal correction from cardiologists.

PMID- 26210410
TI  - HL7 Middleware Framework for Laboratory Notifications for Notifiable Diseases.
AB  - LabSurv is an electronic notification system developed to support laboratories to
      directly notify the results of notifiable disease testing to public health
      services in New Zealand. A direct laboratory notification middleware framework
      was developed to manage the information flow between laboratories and public
      health services. The framework uses an HL7 messaging standard to receive the
      laboratory results and windows services to integrate the results with the cases
      of notifiable diseases within a national electronic surveillance system. This
      paper presents the system design and implementation details of direct laboratory
      notification system in LabSurv. It presents the HL7 messages structure
      implemented in the system. Finally, the performance of the system based on
      implemented framework is analysed and presented to evaluate the efficiency of our
      design. 

PMID- 26210411
TI  - A Registry Framework Enabling Patient-Centred Care.
AB  - Clinical decisions rely on expert knowledge that draws on quality patient
      phenotypic and physiological data. In this regard, systems that can support
      patient-centric care are essential. Patient registries are a key component of
      patient-centre care and can come in many forms such as disease-specific,
      recruitment, clinical, contact, post market and surveillance. There are, however,
      a number of significant challenges to overcome in order to maximise the utility
      of these information management systems to facilitate improved patient-centred
      care. Registries need to be harmonised regionally, nationally and
      internationally. However, the majority are implemented as standalone systems
      without consideration for data standards or system interoperability. Hence the
      task of harmonisation can become daunting. Fortunately, there are strategies to
      address this. In this paper, a disease registry framework is outlined that
      enables efficient deployment of national and international registries that can be
      modified dynamically as registry requirements evolve. This framework provides a
      basis for the development and implementation of data standards and enables
      patients to seamlessly belong to multiple registries. Other significant advances
      include the ability for registry curators to create and manage registries
      themselves without the need to contract software developers, and the concept of a
      registry description language for ease of registry template sharing. 

PMID- 26210412
TI  - The HealthierU Portal for Supporting Behaviour Change and Diet Programs.
AB  - The use of online technologies for supporting participants of behaviour change
      and diet program is a timely and important research direction. We present
      HealthierU, adaptive online portal offering a suite of interactive support tools.
      The portal was evaluated in a 24-week study, which shows that regular reminders
      trigger increased interaction with the portal. We also analyse interaction
      patters conducive to weight loss and discuss possible factors of the attrition
      rates observed in the study. 

PMID- 26210413
TI  - Decision Support Systems and Line Performance: Case of Gold Coast University
      Hospital.
AB  - Computer-based decision support information systems have been promoted for their
      potential to improve physician performance and patient outcomes and support
      clinical decision making. The current case study reported design and
      implementation of a high-level decision support system (DSS) which facilitated
      the flow of data from operational level to top managers and leadership level of
      hospitals. The results shows that development of a DSS improve data connectivity,
      timing, and responsiveness issues via centralised sourcing and storing of
      principal health-related information in the hospital. The implementation of the
      system has resulted in significant enhancements in outpatient waiting times
      management. 

PMID- 26210414
TI  - Considering Governance for Patient Access to E-Medical Records.
AB  - People having access to their medical records could have a transformative
      improvement effect on healthcare delivery and use. Our research aimed to explore
      the concerns and attitudes of giving people electronic access to their medical
      records through patient portals. We conducted 28 semi-structured interviews with
      30 people, asking questions about portal design, organisational implications and
      governance. We report the findings of the governance considerations raised during
      the interviews. These revealed that (1) there is uncertainty about the possible
      design and extent of giving people access to their medical records to view/use,
      (2) existing policies about patient authentication, proxy, and privacy require
      modification, and (3) existing governance structures and functions require
      further examination and adjustment. Future research should include more input
      from patients and health informaticians. 

PMID- 26210415
TI  - Designing Technology for Assessments of CALD Patients.
AB  - Interpreters are required to aid communication between clinicians and culturally
      and linguistically diverse (CALD) patients to ensure appropriate and timely care.
      Demand for interpreting services however, often exceeds supply. A mobile app to
      translate clinical assessment questions in 10 common languages using pictorial,
      written and voice-over prompts to assist patient assessments when interpreters
      are unavailable has been developed. This paper reports on the User Needs Analysis
      that informed the app. The analysis consisted of focus groups with allied health
      clinicians to understand pertinent aspects of initial allied health assessments
      and the communication needs to be addressed in the design of an app-based patient
      assessment tool. Outcomes show that of primary importance to clinicians was the
      ability to not only ask the patients questions, but to communicate information to
      increase understanding of, and ensure compliance with, treatments and
      interventions to promote patient function and comfort. 

PMID- 26210416
TI  - StepKinnection: A Fall Prevention Game Mindfully Designed for the Elderly.
AB  - This paper presents the StepKinnection game, a Kinect-driven stepping game for
      the elderly that delivers stepping exercises to train specific cognitive and
      physical abilities associated with falls. This system combines a set of suitable
      age-related features, meaningful exercise routines and an embedded clinical test
      for fall risk assessment. The combination of these three aspects makes the game
      potentially useful in practice as the game is appealing to the elderly cohort,
      trains one of the most important abilities to prevent falls and at the same time
      allows for a continuous assessment of health outcomes; characteristics not
      available in the literature nor in current commercial games. 

PMID- 26210417
TI  - Le Bon Samaritain: A Community-Based Care Model Supported by Technology.
AB  - BACKGROUND: The effective care and well-being of a community is a challenging
      task especially in an emergency situation. Traditional technology-based silos
      between health and emergency services are challenged by the changing needs of the
      community that could benefit from integrated health and safety services. Low-cost
      smart-home automation solutions, wearable devices and Cloud technology make it
      feasible for communities to interact with each other, and with health and
      emergency services in a timely manner. OBJECTIVES: This paper proposes a new
      community-based care model, supported by technology, that aims at reducing
      healthcare and emergency services costs while allowing community to become
      resilient in response to health and emergency situations. METHODS: We looked at
      models of care in different industries and identified the type of technology that
      can support the suggested new model of care. Two prototypes were developed to
      validate the adequacy of the technology. RESULTS: The result is a new community
      based model of care called 'Le Bon Samaritain'. It relies on a network of people
      called 'Bons Samaritains' willing to help and deal with the basic care and safety
      aspects of their community. Their role is to make sure that people in their
      community receive and understand the messages from emergency and health services.
      The new care model is integrated with existing emergency warning, community and
      health services. CONCLUSION: Le Bon Samaritain model is scalable, community-based
      and can help people feel safer, less isolated and more integrated in their
      community. It could be the key to reduce healthcare cost, increase resilience and
      drive the change for a more integrated emergency and care system.

PMID- 26210418
TI  - An Improved Patient-Specific Mortality Risk Prediction in ICU in a Random Forest
      Classification Framework.
AB  - Dynamic and automatic patient specific prediction of the risk associated with ICU
      mortality may facilitate timely and appropriate intervention of health
      professionals in hospitals. In this work, patient information and time series
      measurements of vital signs and laboratory results from the first 48 hours of ICU
      stays of 4000 adult patients from a publicly available dataset are used to design
      and validate a mortality prediction system. An ensemble of decision trees are
      used to simultaneously predict and associate a risk score against each patient in
      a k-fold validation framework. Risk assessment prediction accuracy of 87% is
      achieved with our model and the results show significant improvement over a
      baseline algorithm of SAPS-I that is commonly used for mortality prediction in
      ICU. The performance of our model is further compared to other state-of-the-art
      algorithms evaluated on the same dataset. 

PMID- 26210419
TI  - Human Activity Recognition from Smart-Phone Sensor Data using a Multi-Class
      Ensemble Learning in Home Monitoring.
AB  - Home monitoring of chronically ill or elderly patient can reduce frequent
      hospitalisations and hence provide improved quality of care at a reduced cost to
      the community, therefore reducing the burden on the healthcare system. Activity
      recognition of such patients is of high importance in such a design. In this
      work, a system for automatic human physical activity recognition from smart-phone
      inertial sensors data is proposed. An ensemble of decision trees framework is
      adopted to train and predict the multi-class human activity system. A comparison
      of our proposed method with a multi-class traditional support vector machine
      shows significant improvement in activity recognition accuracies. 

PMID- 26210420
TI  - Health Informatics and E-health Curriculum for Clinical Health Profession
      Degrees.
AB  - The project reported in this paper models a new approach to making health
      informatics and e-health education widely available to students in a range of
      Australian clinical health profession degrees. The development of a Masters level
      subject uses design-based research to apply educational quality assurance
      practices which are consistent with university qualification frameworks, and with
      clinical health profession education standards; at the same time it gives
      recognition to health informatics as a specialised profession in its own right.
      The paper presents details of (a) design with reference to the Australian
      Qualifications Framework and CHIA competencies, (b) peer review within a three
      university teaching team, (c) external review by experts from the professions,
      (d) cross-institutional interprofessional online learning, (e) methods for
      evaluating student learning experiences and outcomes, and (f) mechanisms for
      making the curriculum openly available to interested parties. The project has
      sought and found demand among clinical health professionals for formal health
      informatics and e-health education that is designed for them. It has helped the
      educators and organisations involved to understand the need for nuanced and
      complementary health informatics educational offerings in Australian
      universities. These insights may aid in further efforts to address substantive
      and systemic challenges that clinical informatics faces in Australia. 

PMID- 26210421
TI  - Automatic Detection of Skin and Subcutaneous Tissue Infections from Primary Care
      Electronic Medical Records.
AB  - INTRODUCTION: Skin and subcutaneous tissue infections (SSTI) are common
      conditions that cause avoidable hospitalisation in New Zealand. As part of a
      program to improve the management of SSTI in primary care, electronic medical
      records (EMR) of four Auckland general practices were analysed to identify SSTI
      occurrences in the last three years. METHODS: An ontology for SSTI risks,
      manifestation and treatment was created based on literature and guidelines. An
      SSTI identification algorithm was developed examining EMR data for skin swab
      tests, diagnoses (READ codes) and textual clinical notes. RESULTS: High
      occurrence and recurrence rates in those aged 20 or younger were found. Due to
      low usage of READ coding and laboratory tests, 65% of SSTI occurrences were
      identified by notes. However, 91% of all identified SSTI occurrences were
      appropriately treated with oral/topical antibiotics according to prescription
      records in the EMR. The F1 score of the analysis algorithm is 0.76 using manual
      review as gold standard. DISCUSSION AND CONCLUSION: The SSTI identification
      algorithm shows a reasonable accuracy suggesting the feasibility of automatic
      detecting SSTI occurrences using clinical data that are routinely collected in
      healthcare delivery.

PMID- 26210422
TI  - Incidence Rate of Prediabetes: An Analysis of New Zealand Primary Care Data.
AB  - INTRODUCTION: Diabetes is a common disease affecting 9% of the adult population
      worldwide. People with impaired glucose tolerance ('prediabetes') are at high
      risk of progressing to type 2 diabetes. METHODS: To understand prediabetes
      incidence rate, we analysed the electronic medical records (EMR) from 14 New
      Zealand general practices regarding patients aged >=20 years and enrolled with
      the practices between 2009 and 2012. Prediabetes incidence rate was calculated by
      the number of patients with an initial HbA1c of 41-49 mmol/mol in 2011 among
      those who had not been diagnosed or treated for diabetes. RESULTS: 28,192 adults
      were included in the analysis, 11% of this cohort had diabetes before 2011. 1,276
      new cases of prediabetes were identified in 2011, giving a 5.0% incidence rate.
      The relative risk (RR) for prediabetes was increased for the Maori and Pacific
      groups versus non-Maori/non-Pacific people, with RR of 1.97 in the younger age
      groups (<50 years) and RR of 1.42 in the 50+ group. The RR for having
      uncontrolled HbA1c (highest HbA1c in 2011 >=65 mmol/mol) among the whole adult
      population was also increased for the Maori and Pacific groups versus non
      Maori/non-Pacific people (RR=3.35 among those <50 years, RR=4.35 in the 50+
      group). DISCUSSION AND CONCLUSION: EMR analysis identified an alarming incidence
      rate of prediabetes, especially among Maori and Pacific groups, highlighting the
      need to better prevent and manage the condition.

PMID- 26210423
TI  - Automated Classification of Clinical Incident Types.
AB  - We consider the task of automatic classification of clinical incident reports
      using machine learning methods. Our data consists of 5448 clinical incident
      reports collected from the Incident Information Management System used by 7
      hospitals in the state of New South Wales in Australia. We evaluate the
      performance of four classification algorithms: decision tree, naive Bayes,
      multinomial naive Bayes and support vector machine. We initially consider 13
      classes (incident types) that were then reduced to 12, and show that it is
      possible to build accurate classifiers. The most accurate classifier was the
      multinomial naive Bayes achieving accuracy of 80.44% and AUC of 0.91. We also
      investigate the effect of class labelling by an ordinary clinician and an expert,
      and show that when the data is labelled by an expert the classification
      performance of all classifiers improves. We found that again the best classifier
      was multinomial naive Bayes achieving accuracy of 81.32% and AUC of 0.97. Our
      results show that some classes in the Incident Information Management System such
      as Primary Care are not distinct and their removal can improve performance; some
      other classes such as Aggression Victim are easier to classify than others such
      as Behavior and Human Performance. In summary, we show that the classification
      performance can be improved by expert class labelling of the training data,
      removing classes that are not well defined and selecting appropriate machine
      learning classifiers. 

PMID- 26210424
TI  - Model Selection and Variable Aggregation of Australian Hospital Data.
AB  - BACKGROUND: Hospital administrative data commonly consist of hundreds of
      variables with many consisting of hundreds, if not thousands, of distinct
      categories, especially for disease groups. Conventional approaches to develop
      regression models for prediction either fail completely due to multicollinearity
      or sparsity issues or take too long and consume too many computer resources.
      METHODS: We demonstrate how regularisation and variable aggregation techniques
      such as Elastic Net can overcome some of these problems. Parameter estimates from
      univariate generalised linear models (GLM) and Elastic Net models were used to
      aggregate disease groups into a more manageable number and predict the
      probability of mortality for a given patient. RESULTS: When employed for variable
      aggregation and variable selection, Elastic Net models ran at least four times
      faster than GLMs, though producing a less discriminative model. When applied to
      final models for predicting hospital mortality, though, both Elastic Net and GLM
      models demonstrated similar predictive power and efficiently solved an otherwise
      complex problem. CONCLUSION: Elastic Net regularisation and variable aggregation
      provide an efficient mechanism for solving healthcare modelling problems.

PMID- 26210425
TI  - The Personally Controlled Electronic Health Record (PCEHR) for Adults with Severe
      Communication Impairments: Findings of Pilot Research.
AB  - To date, there is little information in the literature to guide the provision of
      supports for using the Personally Controlled Electronic Health Record (PCEHR) in
      populations with severe communication impairments associated with a range of
      disabilities. In this paper we will (a) outline the rationale for use of PCEHR in
      these populations by providing an overview of relevant research to date, and (b)
      present results of three integrated pilot studies aiming to investigate the
      barriers to and facilitators for PCEHR use by people with severe communication
      impairments and their service providers. Finally, we will present directions for
      future research on use of PCEHR by people with severe communication impairments. 

PMID- 26210426
TI  - Measuring Data Quality Through a Source Data Verification Audit in a Clinical
      Research Setting.
AB  - Health data has long been scrutinised in relation to data quality and integrity
      problems. Currently, no internationally accepted or "gold standard" method exists
      measuring data quality and error rates within datasets. We conducted a source
      data verification (SDV) audit on a prospective clinical trial dataset. An audit
      plan was applied to conduct 100% manual verification checks on a 10% random
      sample of participant files. A quality assurance rule was developed, whereby if
      >5% of data variables were incorrect a second 10% random sample would be
      extracted from the trial data set. Error was coded: correct, incorrect (valid or
      invalid), not recorded or not entered. Audit-1 had a total error of 33% and audit
      2 36%. The physiological section was the only audit section to have <5% error.
      Data not recorded to case report forms had the greatest impact on error
      calculations. A significant association (p=0.00) was found between audit-1 and
      audit-2 and whether or not data was deemed correct or incorrect. Our study
      developed a straightforward method to perform a SDV audit. An audit rule was
      identified and error coding was implemented. Findings demonstrate that monitoring
      data quality by a SDV audit can identify data quality and integrity issues within
      clinical research settings allowing quality improvement to be made. The authors
      suggest this approach be implemented for future research. 

PMID- 26210427
TI  - The Hare and the Hortoise: The Potential Versus the Reality of eTP
      Implementation.
AB  - In a health system increasingly driven by cost constraints, there is a focus on
      improved electronic transfer of information to support healthcare delivery. One
      area of healthcare that has moved more quickly than others to achieve this is
      prescribing in the primary care environment. Whilst the move to electronic
      transfer of prescriptions has reduced transcription errors, the regulatory
      environment persists with handwritten signatures. This constraint, whilst
      addressed slowly with technology solutions, needs support from legislative
      change. The ultimate step is to have a secure mobile model, which would support
      the move to a fully-electronic, paperless transaction model. 

PMID- 26210428
TI  - Use of Smartphones to Estimate Carbohydrates in Foods for Diabetes Management.
AB  - Over 380 million adults worldwide are currently living with diabetes and the
      number has been projected to reach 590 million by 2035. Uncontrolled diabetes
      often lead to complications, disability, and early death. In the management of
      diabetes, dietary intervention to control carbohydrate intake is essential to
      help manage daily blood glucose level within a recommended range. The
      intervention traditionally relies on a self-report to estimate carbohydrate
      intake through a paper based diary. The traditional approach is known to be
      inaccurate, inconvenient, and resource intensive. Additionally, patients often
      require a long term of learning or training to achieve a certain level of
      accuracy and reliability. To address these issues, we propose a design of a
      smartphone application that automatically estimates carbohydrate intake from food
      images. The application uses imaging processing techniques to classify food type,
      estimate food volume, and accordingly calculate the amount of carbohydrates. To
      examine the proof of concept, a small fruit database was created to train a
      classification algorithm implemented in the application. Consequently, a set of
      fruit photos (n=6) from a real smartphone were applied to evaluate the accuracy
      of the carbohydrate estimation. This study demonstrates the potential to use
      smartphones to improve dietary intervention, although further studies are needed
      to improve the accuracy, and extend the capability of the smartphone application
      to analyse broader food contents. 

PMID- 26210429
TI  - Chat-Bots for People with Parkinson's Disease: Science Fiction or Reality?
AB  - People with Parkinson's disease are known to have difficulties in language and
      communication. This paper proposes the use of an artificial conversational agent,
      commonly known as a chat-bot that runs on a smart-phone device and performs two
      way conversation with the user. In this paper, initial work on a Parkinson's
      disease themed chat-bot that interacts with the user relative to their symptoms
      is presented. Potential dialogues are provided to illustrate the various roles
      chat-bots can play in the management of Parkinson's disease. The chat-bot can be
      used for measuring voice and communication outcomes during the daily life of the
      user, and for gaining information about challenges encountered. Moreover, it is
      anticipated that it may also have an educational and support role. The chat-bot
      is now ready for usability testing with a clinical population. 

PMID- 26210430
TI  - The Relationship between Using Electronic Health Records and Meeting
      Accreditation Standards for Client Safety in Residential Aged Care Homes.
AB  - This study aims to identify the benefits of using electronic health records (EHR)
      for client safety in residential aged care (RAC) homes. The aged care
      accreditation reports published between 27 April 2011 and 3 December 2013 were
      downloaded and analysed. It could be seen from these reports that only
      1,031(37.45%) RAC homes in Australia had adopted an EHR system by 2013. 13 RAC
      homes failed one or more accreditation standards. Only one of these was using an
      EHR system and this one met the accreditation standards on information systems.
      Our study provides empirical evidence to suggest that adopting and using EHR can
      be one of the effective organisational mechanisms to meeting accreditation
      standards in RAC homes. 

PMID- 26210431
TI  - A Pilot Study to Improve Access to Eye Care Services for Patients in Rural India
      by Implementing Community Ophthalmology through Innovative Telehealth Technology.
AB  - OBJECTIVE: To inform about a very unique and first of its kind telehealth pilot
      study in India that has provided virtual telehealth consultation to eye care
      patients in low resource at remote villages. BACKGROUND: Provision of Access to
      eye care services in remote population is always challenging due to pragmatic
      reasons. Advances in Telehealth technologies have provided an opportunity to
      improve access to remote population. However, current Telehealth technologies are
      limited to face-to-face video consultation only. We inform about a pilot study
      that illustrates real-time imaging access to ophthalmologists. Our innovative
      software led technology solution allowed screening of patients with varying
      ocular conditions. METHODS: Eye camps were conducted in 2 districts in South
      India over a 12-month period in 2014. Total of 196 eye camps were conducted.
      Total of 19,634 patients attended the eye camps. Innovative software was used to
      conduct consultation with the ophthalmologist located in the city hospital. The
      software enabled virtual visit and allowed instant sharing of fundus camera
      images for assessment and diagnosis. RESULTS: About 71% of the patients were
      found to have Refractive Error problems, 15% of them were found to have cataract,
      7% of the patients were diagnosed to have Retina problems and 7% of the patients
      were found to have other ocular diseases. The patients requiring cataract surgery
      were immediately transferred to city hospital for treatment. Software led
      assessment of fundus camera images assisted in identifying retinal eye diseases.
      CONCLUSION: Our real-time virtual visit software assisted in specialist care
      provision and illustrated a novel tele health solution for low resource
      population.

PMID- 26210432
TI  - Improving Video Based Heart Rate Monitoring.
AB  - Non-contact measurements of cardiac pulse can provide robust measurement of heart
      rate (HR) without the annoyance of attaching electrodes to the body. In this
      paper we explore a novel and reliable method to carry out video-based HR
      estimation and propose various performance improvement over existing approaches.
      The investigated method uses Independent Component Analysis (ICA) to detect the
      underlying HR signal from a mixed source signal present in the RGB channels of
      the image. The original ICA algorithm was implemented and several modifications
      were explored in order to determine which one could be optimal for accurate HR
      estimation. Using statistical analysis, we compared the cardiac pulse rate
      estimation from the different methods under comparison on the extracted videos to
      a commercially available oximeter. We found that some of these methods are quite
      effective and efficient in terms of improving accuracy and latency of the system.
      We have made the code of our algorithms openly available to the scientific
      community so that other researchers can explore how to integrate video-based HR
      monitoring in novel health technology applications. We conclude by noting that
      recent advances in video-based HR monitoring permit computers to be aware of a
      user's psychophysiological status in real time. 

PMID- 26210433
TI  - Impact of Physician Community Structure on Healthcare Outcomes.
AB  - There is a substantial variation in healthcare spending and readmission rate for
      individuals having admissions to different hospitals. This study assessed how the
      community structure of physician collaboration networks that evolve during the
      period of providing healthcare services to hospitalised patients contribute to
      this variation. A physician collaboration network is said to have a community
      structure if the nodes (i.e. physicians) of that network can be easily grouped
      into sets of nodes such that each set of nodes is densely connected internally
      but sparsely connected between groups. This study constructed physician
      collaboration networks based on patient-sharing ties among physicians who
      provided healthcare services to hospitalised patients. An administrative health
      insurance claim dataset was utilised to extract patient-sharing ties among
      physicians. Simple linear regression models were estimated to assess the impact
      of the community structure of physician collaboration networks on the healthcare
      outcome measures (i.e. readmission rate and hospitalisation cost). From these
      models, this study found that the structure of a physician community has
      significant impact on readmission rate and hospitalisation cost. Healthcare
      administrators or managers could consider this finding in developing effective
      and efficient healthcare environments in their respective healthcare
      organisations. 

PMID- 26210434
TI  - Educating the Health Informatics Professional: The Impact of an Academic Program.
AB  - INTRODUCTION: The successful implementation and utilisation of electronic health
      information systems is dependent on a highly knowledgeable and skilled workforce.
      In Australia there is a range of education and training opportunities that seeks
      to meet these workforce needs. This range of programs reflects both the multi
      disciplinary characteristic of health informatics and its wide application within
      the healthcare environment. We need to discuss the role of each program or type
      of program in developing a skilled and knowledgeable workforce, and in expanding
      the knowledge base of the discipline. This paper contributes to such a discussion
      by describing a pilot study that focused specifically on the role/impact of the
      University of Tasmania academic health informatics program. METHODS: The study
      comprised an anonymous on-line survey followed by a small number of interviews.
      The online survey included closed questions which gathered quantitative data
      about Quantitative data were analysed using appropriate numerical methods such as
      response counts and/or percentages. Open-ended questions were analysed using
      thematic analysis. RESULTS: Qualitative data indicated that course graduates
      reside in every state and territory, with the majority being employed by the
      various state health services. The majority of respondents had moved into health
      informatics professions or into senior positions in health informatics. Eighty
      percent attributed this directly to their participation in the course.
      Respondents indicated a strong socio-technical orientation in their approach to
      health informatics. DISCUSSION: The program appears to be having an impact on the
      health informatics workforce, particularly in promoting a strong socio-technical
      focus. CONCLUSION: Evaluation of health informatics programs would enable the
      development of a comprehensive and complementary network of offerings that would
      meet the diverse needs for health informatics professionals in the healthcare and
      academic environment.

PMID- 26210435
TI  - Development and Practice of Store-and-Forward Telehealth Systems in Ophthalmology
      Dental and Emergency.
AB  - Store-and-forward (S&F) telehealth system has been becoming an increasing
      application in remote medical consultations. In this paper, we will introduce
      three novel S&F telehealth systems we developed for ophthalmological, dental and
      emergency applications. We will explain the general system architecture of the
      S&F systems. Then we will focus on the specific features and components in each
      system implemented for meeting their respective clinical requirements. In the
      final section we will present further implementation details and practices and
      provide discussions. 

PMID- 26210438
TI  - Preface. Driving reform: Digital health is everyone's business.

PMID- 26210439
TI  - Inhibition of cisplatin-resistance by RNA interference targeting metallothionein
      using reducible oligo-peptoplex.
AB  - Effective intracellular level of a platinum anti-cancer drug, cisplatin,
      following repeated injections can be decreased either by the active efflux via
      ATP pump or by interactions with glutathione and metallothionein. Cisplatin in
      cytoplasm preferably binds to cysteine-rich proteins such as glutathione and
      metallothionein (MT). Detoxification of cisplatin by intracellular thiol
      containing proteins has been considered to be major hurdles to overcome. The
      short hairpin RNA targeting MT (shMT) was tested to down-regulate MT and recover
      cisplatin resistance. A reducible polymer, poly(oligo-d-arginine) (rPOA), formed
      stable complex with shMT and demonstrated superior transfection efficiency.
      Efficient transfection of shMT/rPOA oligo-peptoplexes was found to significantly
      inhibit MT over-expression, resulting in 45% decrease of cell viability compared
      to the cisplatin alone group. This decrease was mediated by the synergistic
      effect of shMT/rPOA oligo-peptoplex and cisplatin. Co-administration of shMT/rPOA
      oligo-peptoplex and cisplatin in in vivo tumor model showed noticeable tumor
      suppressing effect by inducing reversal of cisplatin resistance following
      effective intracellular delivery of shMT by rPOA. Combination therapy through co
      administration of shMT/rPOA oligo-peptoplex and cisplatin was found to
      effectively reverse cisplatin resistance by RNA interference and consequently
      improve anti-cancer activity of cisplatin. 

PMID- 26210440
TI  - Cell membrane-camouflaged nanoparticles for drug delivery.
AB  - Nanoparticles can preferentially accumulate at sites of action and hold great
      promise to improve the therapeutic index of many drugs. While conventional
      methods of nanocarrier-mediated drug delivery have focused on primarily synthetic
      approaches, engineering strategies that combine synthetic nanoparticles with
      natural biomaterials have recently gained much attention. In particular, cell
      membrane-camouflaged nanoparticles are a new class of biomimetic nanoparticles
      that combine the unique functionalities of cellular membranes and engineering
      versatility of synthetic nanomaterials for effective delivery of therapeutic
      agents. Herein, we report on the recent progress on cell membrane-coated
      nanoparticles for drug delivery. In particular, we highlight three areas: (i)
      prolonging systemic circulation via cell membrane coating, (ii) cell-specific
      targeting via cell membrane coating, and (iii) applications of cell membrane
      coating for drug delivery. The cell membrane-camouflaged nanoparticle platform
      has emerged as a novel delivery strategy with the potential to improve the
      therapeutic efficacy for the treatment of a variety of diseases. 

PMID- 26210441
TI  - A novel in vitro method to model the fate of subcutaneously administered
      biopharmaceuticals and associated formulation components.
AB  - Subcutaneous (SC) injection is becoming a more common route for the
      administration of biopharmaceuticals. Currently, there is no reliable in vitro
      method that can be used to anticipate the in vivo performance of a
      biopharmaceutical formulation intended for SC injection. Nor is there an animal
      model that can predict in vivo outcomes such as bioavailability in humans. We
      address this unmet need by the development of a novel in vitro system, termed
      Scissor (Subcutaneous Injection Site Simulator). The system models environmental
      changes that a biopharmaceutical could experience as it transitions from
      conditions of a drug product formulation to the homeostatic state of the
      hypodermis following SC injection. Scissor uses a dialysis-based injection
      chamber, which can incorporate various concentrations and combinations of
      acellular extracellular matrix (ECM) components that may affect the release of a
      biopharmaceutical from the SC injection site. This chamber is immersed in a
      container of a bicarbonate-based physiological buffer that mimics the SC
      injection site and the infinite sink of the body. Such an arrangement allows for
      real-time monitoring of the biopharmaceutical within the injection chamber, and
      can be used to characterize physicochemical changes of the drug and its
      interactions with ECM components. Movement of a biopharmaceutical from the
      injection chamber to the infinite sink compartment simulates the drug migration
      from the injection site and uptake by the blood and/or lymph capillaries. Here,
      we present an initial evaluation of the Scissor system using the ECM element
      hyaluronic acid and test formulations of insulin and four different monoclonal
      antibodies. Our findings suggest that Scissor can provide a tractable method to
      examine the potential fate of a biopharmaceutical formulation after its SC
      injection in humans and that this approach may provide a reliable and
      representative alternative to animal testing for the initial screening of SC
      formulations. 

PMID- 26210443
TI  - Effect of Irradiation on Incidence of Post-Transplant Lymphoproliferative
      Disorder after Hematopoietic Cell Transplantation in Miniature Swine.
AB  - Post-transplant lymphoproliferative disease (PTLD) is a major complication of
      clinical organ and cell transplantation. Conditioning and immunosuppressive
      regimens that significantly impair T cell immunity, including depleting
      antibodies and calcineurin inhibitors, increase the risk of PTLD after
      transplantation. Swine PTLD has been shown to closely resemble human PTLD in
      morphology, histology, and viral-driven reactivation of B cells. Previously, we
      reported high incidences of PTLD after hematopoietic cell transplantation (HCT)
      in miniature swine recipients conditioned with thymic irradiation (TI) in
      addition to T cell depletion and cyclosporine A monotherapy after
      transplantation. Replacement of TI with 100 cGy of total body irradiation
      resulted in similar numbers of B cells early post-transplantation, greater
      numbers of T cells at day 0, and markedly decreased incidence of PTLD, suggesting
      that a threshold number of T cells may be necessary to prevent subsequent B cell
      proliferation and development of overt PTLD. Results from this large cohort of
      animals provide insight into the important effect of irradiation and T cell
      immunity on the incidence of PTLD after HCT and reinforce the pig model as a
      valuable tool for the study of PTLD and HCT.

PMID- 26210442
TI  - Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous
      Infusion in Allogeneic Transplant Patients.
AB  - Intensive chemotherapy or chemotherapy plus irradiation and allogeneic stem cell
      transplantation can be curative for patients with hematologic diseases. Reduced
      intensity transplants can also achieve cure and result in less treatment-related
      mortality but higher relapse rates. Thus, optimizing the conditioning regimens
      used in allogeneic transplantation remains an important goal. We conducted a
      phase I/II trial to determine the maximum tolerated dose (MTD) and dose-limiting
      toxicities (DLTs) of a continuous infusion of busulfan over 90 hours in
      conjunction with fludarabine followed by allogeneic related or unrelated donor
      transplant. Fifty-four patients with advanced hematologic malignancies were
      enrolled on this study. The MTD was identified as a 24-hour area under the curve
      (AUC) of approximately 7095 MUM/min, which represents a 43% increase over the
      standard total daily AUC dose of 4800 MUM/min given by intermittent schedules.
      DLTs at doses over 8000 MUM/min were identified by a desquamative skin rash and
      mucositis. No dose-related increase in hepatic, pulmonary, or other organ
      toxicities were seen, whereas efficacy appeared to be improved at higher dose
      levels. Continuous-infusion busulfan with intermittent fludarabine provides an
      alternative treatment strategy that is generally well tolerated and permits an
      increase in total busulfan dose with encouraging efficacy. (NCI study no.
      NCT00448357.).

PMID- 26210444
TI  - Attendance patterns and chlamydia and gonorrhoea testing among young people in
      Aboriginal primary health centres in New South Wales, Australia.
AB  - Background To inform a sexual health quality improvement program we examined
      chlamydia and gonorrhoea testing rates among 15-29 year olds attending Aboriginal
      Community Controlled Health Services (ACCHS) in New South Wales, Australia, and
      factors associated with chlamydia and gonorrhoea testing. METHODS: From 2009 to
      2011, consultation and testing data were extracted from four ACCHS. Over the
      study period, we calculated the median number of consultations per person and
      interquartile range (IQR), the proportion attending (overall and annually), the
      proportion tested for chlamydia and gonorrhoea, and those who tested positive. We
      examined factors associated with chlamydia and gonorrhoea testing using logistic
      regression. RESULTS: Overall, 2896 15-29-year-olds attended the ACCHSs, 1223 were
      male and 1673 were female. The median number of consultations was five (IQR 2
      12), four (IQR 1-8) for males and seven (IQR 3-14) for females (P<0.001).
      Nineteen percent of males and 32% of females attended in each year of the study
      (P<0.001). Overall, 17% were tested for chlamydia (10% of males and 22% of
      females, P<0.001), and 7% were tested annually (3% of males and 11% of females,
      P<0.001). Findings were similar for gonorrhoea testing. In the study period, 10%
      tested positive for chlamydia (14% of males and 9% of females, P<0.001) and 0.6%
      for gonorrhoea. Factors independently associated with chlamydia testing were
      being female (adjusted odds ratio (AOR) 2.64, 95% confidence interval (CI) 2.07
      3.36), being 20-24 years old (AOR: 1.58, 95% CI: 1.20-2.08), and having >3
      consultations (AOR: 16.97, 95% CI: 10.32-27.92). CONCLUSIONS: More frequent
      attendance was strongly associated with being tested for chlamydia and
      gonorrhoea. To increase testing, ACCHS could develop testing strategies and
      encourage young people to attend more frequently.

PMID- 26210445
TI  - Redox regulation of metabolic and signaling pathways by thioredoxin and
      glutaredoxin in NOS-3 overexpressing hepatoblastoma cells.
AB  - Nitric oxide (NO) plays relevant roles in signal transduction in physiopathology
      and its effects are dependent on several environmental factors. NO has both pro
      apoptotic and anti-apoptotic functions but the molecular mechanisms responsible
      for these opposite effects are not fully understood. The action of NO occurs
      mainly through redox changes in target proteins, particularly by S-nitrosylation
      of reactive cysteine residues. Thioredoxin (Trx) and glutaredoxin (Grx) systems
      are the main cellular controllers of the thiolic redox state of proteins exerting
      controversial effects on apoptosis with consequences for the resistance to or the
      development of cancer. The aim of this study was to ascertain whether Trx and/or
      Grx systems mediate the antiproliferative effect of NO on hepatoblastoma cells by
      modulating the redox-state of key proteins. Proliferation decreased and apoptosis
      increased in HepG2 cells overexpressing Nitric Oxide Synthase-3 (NOS-3) as a
      result of multilevel cellular responses to the oxidative environment generated by
      NO. Enzyme levels and cysteine redox state at several metabolic checkpoints were
      consistent with prominence of the pentose phosphate pathway to direct the
      metabolic flux toward NADPH for antioxidant defense and lowering of nucleotide
      biosynthesis and hence proliferation. Proteins involved in cell survival
      pathways, proteins of the redoxin systems and phosphorylation of MAPK were all
      significantly increased accompanied by a shift of the thiolic redox state of
      Akt1, Trx1 and Grx1 to more oxidized. Silencing of Trx1 and Grx1 neutralized the
      increases in CD95, Akt1 and pAkt levels induced by NO and produced a marked
      increase in caspase-3 and -8 activities in both control and NOS-3 overexpressing
      cells concomitant with a decrease in the number of cells. These results
      demonstrate that the antiproliferative effect of NO is actually hampered by Trx1
      and Grx1 and support the strategy of weakening the thiolic antioxidant defenses
      when designing new antitumoral therapies. 

PMID- 26210447
TI  - Quantification of Ataxin-3 and Ataxin-7 aggregates formed in vivo in Drosophila
      reveals a threshold of aggregated polyglutamine proteins associated with cellular
      toxicity.
AB  - Polyglutamine diseases are nine dominantly inherited neurodegenerative
      pathologies caused by the expansion of a polyglutamine domain in a protein
      responsible for the disease. This expansion leads to protein aggregation,
      inclusion formation and toxicity. Despite numerous studies focusing on the
      subject, whether soluble polyglutamine proteins are responsible for toxicity or
      not remains debated. To focus on this matter, we evaluated the level of soluble
      and insoluble truncated pathological Ataxin-3 in vivo in Drosophila, in presence
      or absence of two suppressors (i.e. Hsp70 and non-pathological Ataxin-3) and
      along aging. Suppressing truncated Ataxin-3-induced toxicity resulted in a
      lowered level of aggregated polyglutamine protein. Interestingly, aggregates
      accumulated as flies aged and reached a maximum level when cell death was
      detected. Our results were similar with two other pathological polyglutamine
      proteins, namely truncated Ataxin-7 and full-length Ataxin-3. Our data suggest
      that accumulation of insoluble aggregates beyond a critical threshold could be
      responsible for toxicity. 

PMID- 26210448
TI  - MiR-21 promoted proliferation and migration in hepatocellular carcinoma through
      negative regulation of Navigator-3.
AB  - MicroRNA-21 (miR-21) has been well-established and found to be over-expressed in
      various human cancers and has been associated with hepatocellular carcinoma (HCC)
      progression. However, the underlying mechanism of miR-21 involvement in the
      development and progression of HCC remains to be understood. In the present
      study, we firstly identified that the Navigator-3 (NAV-3) gene as a novel direct
      target of miR-21. Knock-down of NAV-3 using shRNA can rescue the effects of anti
      miR-21 inhibitor in HCC cell lines, whereas re-expression of miR-21 using
      transfection with miR-21 mimics phenocopied the NAV-3 knock-down model.
      Additionally, miR-21 levels inversely correlated with NAV-3 both in HCC cells and
      tissues. Knock-down of NAV-3 promoted both the proliferation and migration in HCC
      cells. Together, our findings suggest an important role for miR-21 in the
      progression of HCC, which negatively regulated Navigator-3 in the migration of
      HCC. 

PMID- 26210449
TI  - Clinical potential of miR-3651 as a novel prognostic biomarker for esophageal
      squamous cell cancer.
AB  - Accumulating evidence indicates that dysregulated microRNA-3651(miR-3651) is
      involved in tumorigenesis and cancer progression. In this study, we investigated
      the expression of miR-3651 in esophageal squamous cell cancer(ESCC) and its
      relationship with tumor progression and clinical prognosis. The expression level
      of miR-3651 was examined by quantitative Real-time PCR (qRT-PCR) in fresh ESCC
      tissues and FFPE tissues. The correlation between miR-3651 expression and
      clinical features and prognosis were statistically analyzed. The results showed
      that the miR-3651 expression was significantly down-regulated in tumor tissues
      compared with the paracancerous tissues. Moreover, miR-3651 expression was
      negatively correlated with T stage of ESCC (P = 0.022) and tumor length (P =
      0.015). Kaplan-Meier analysis demonstrated that low miR-3651 expression level was
      associated with poorer overall survival (OS) (P = 0.004) and disease-free
      survival (DFS) (P = 0.001). Multivariate analysis identified miR-3651 expression
      as independent prognostic factor for OS and DFS (P = 0.001 and P = 0.001, resp.).
      Further stratified analysis revealed the significant association between low miR
      3651 expression and worse survival in early patients, but not in the advanced
      patients. Taken together, miR-3651 was down-regulated in cancerous tissues of
      ESCC. It may play an important role in cancer progression and could be used as an
      independent prognostic biomarker for ESCC patients. 

PMID- 26210450
TI  - A novel method to visually determine the intracellular pH of xenografted tumor in
      vivo by utilizing fluorescent protein as an indicator.
AB  - The alkalization of intracellular pH (pHin) advances together with enhancement of
      aerobic glycolysis within tumor cells (the Warburg effect), and that is
      responsible for the progression of tumor malignancy together with hypoxia and
      angiogenesis. But how they correlate each other during tumor growth is poorly
      understood, partly due to the lack of suitable imaging methods. In present study,
      we propose a novel method to visually determine the pHin of tumor xenograft model
      from fluorescent image ratios. We utilized tandemly-linked two fluorescent
      proteins as a pH indicator; yellow fluorescent protein (YFP, pH sensitive) as an
      indicator, and red fluorescent protein (RFP, pH insensitive) as a reference. This
      method can eliminate the influence of optical factors from tissue as well as of
      the diverse expression level of pH indicator in the grafted cells. In addition,
      that can be operated by filter-based fluorescent imagers that are generally used
      in small animal study. The efficacy of the pH indicator, RFP-YFP, was confirmed
      by studies using recombinant protein in vitro and HeLa cells expressing RFP-YFP
      in vivo. Furthermore, we prepared nude mice subcutaneously xenografted HeLa cells
      expressing RFP-YFP cells as tumor model. The image ratios (YFP/RFP) of the tumor
      at the day 5 after surgery clearly showed the heterogeneous distribution of
      diverse pHin cells in the tumor tissue. Concomitantly acquired angiography using
      near-infrared fluorescence (680 nm for emission) also indicated that the relative
      alkaline pHin cells located in the region far from tumor vessels in which tumor
      aerobic glycolysis would be facilitated by progression of hypoxia and nutrient
      starvation. Applying the present method for a multi-wavelength imaging concerning
      pO2 and/or nutrient starvation states in addition to pHin and angiogenesis would
      provide valuable information about complicated alteration of tumoral cell states
      during tumorigenesis. 

PMID- 26210451
TI  - Crystal structure analysis of ornithine transcarbamylase from Thermus
      thermophilus --HB8 provides insights on the plasticity of the active site.
AB  - The enzymatic biosynthesis of L-arginine involves complex, sequential action of
      many enzymes and ornithine transcarbamylase (OTCase) is one of the essential
      enzymes in the pathway. In mammals OTCase is part of the urea cycle. Arginine is
      used in a variety of pharmaceutical and industrial applications and therefore
      engineering arginine biosynthesis pathway for overproduction of arginine has
      gained importance. On the other hand, it was found that detrimental mutations in
      the human OTCase gene resulted clinical hyperammonemia, with subsequent
      neurological damage. Therefore a better understanding of the structure-function
      relationship of this enzyme from various sources could be useful for modifying
      its enzymatic action. Here we report the structure of ornithine transcarbamylase
      of Thermus thermophilus HB8 (aTtOTCase) at 2.0 A resolution. On comparison with
      its homologs, aTtOTCase showed maximum variation at the substrate binding loops
      namely 80s and SMG/240s loops. The active site geometry of aTtOTCase is unique
      among its homologs where the side chain of certain residues (Leu57, Arg58 and
      Arg288) is oriented differently. To study the structural insights of substrate
      binding in aTtOTCase, docking of carbamoyl phosphate (CP) and ornithine (Orn) was
      carried out sequentially. Both substrates were unable to bind in a proper
      orientation in the active site pocket and this could be due to the differently
      oriented side chains. This suggests that the active site geometry should also
      undergo fine tuning besides the large structural changes as the enzyme switches
      from completely open to a substrate bound closed state.

PMID- 26210446
TI  - Genetic disorders coupled to ROS deficiency.
AB  - Maintaining the redox balance between generation and elimination of reactive
      oxygen species (ROS) is critical for health. Disturbances such as continuously
      elevated ROS levels will result in oxidative stress and development of disease,
      but likewise, insufficient ROS production will be detrimental to health. Reduced
      or even complete loss of ROS generation originates mainly from inactivating
      variants in genes encoding for NADPH oxidase complexes. In particular, deficiency
      in phagocyte Nox2 oxidase function due to genetic variants (CYBB, CYBA, NCF1,
      NCF2, NCF4) has been recognized as a direct cause of chronic granulomatous
      disease (CGD), an inherited immune disorder. More recently, additional diseases
      have been linked to functionally altered variants in genes encoding for other
      NADPH oxidases, such as for DUOX2/DUOXA2 in congenital hypothyroidism, or for the
      Nox2 complex, NOX1 and DUOX2 as risk factors for inflammatory bowel disease. A
      comprehensive overview of novel developments in terms of Nox/Duox-deficiency
      disorders is presented, combined with insights gained from structure-function
      studies that will aid in predicting functional defects of clinical variants. 

PMID- 26210452
TI  - Signal transduction and downregulation of C-MET in HGF stimulated low and highly
      metastatic human osteosarcoma cells.
AB  - The poor outcome of osteosarcoma (OS), particularly in patients with metastatic
      disease and a five-year survival rate of only 20%, asks for more effective
      therapeutic strategies targeting malignancy-promoting mechanisms. Dysregulation
      of C-MET, its ligand hepatocyte growth factor (HGF) and the fusion oncogene
      product TPR-MET, first identified in human MNNG-HOS OS cells, have been described
      as cancer-causing factors in human cancers. Here, the expression of these
      molecules at the mRNA and the protein level and of HGF-stimulated signaling and
      downregulation of C-MET was compared in the parental low metastatic HOS and MG63
      cell lines and the respective highly metastatic MNNG-HOS and 143B and the MG63-M6
      and MG63-M8 sublines. Interestingly, expression of TPR-MET was only observed in
      MNNG-HOS cells. HGF stimulated the phosphorylation of Akt and Erk1/2 in all cell
      lines investigated, but phospho-Stat3 remained at basal levels. Downregulation of
      HGF-stimulated Akt and Erk1/2 phosphorylation was much faster in the HGF
      expressing MG63-M8 cells than in HOS cells. Degradation of HGF-activated C-MET
      occurred predominantly through the proteasomal and to a lesser extent the
      lysosomal pathway in the cell lines investigated. Thus, HGF-stimulated Akt and
      Erk1/2 signaling as well as proteasomal degradation of HGF activated C-MET are
      potential therapeutic targets in OS. 

PMID- 26210453
TI  - Downregulation of miRNA-30c and miR-203a is associated with hepatitis C virus
      core protein-induced epithelial-mesenchymal transition in normal hepatocytes and
      hepatocellular carcinoma cells.
AB  - Hepatitis C virus (HCV) Core protein has been demonstrated to induce epithelial
      mesenchymal transition (EMT) and is associated with cancer progression of
      hepatocellular carcinoma (HCC). However, how the Core protein regulates EMT is
      still unclear. In this study, HCV Core protein was overexpressed by an
      adenovirus. The protein levels of EMT markers were measured by Western blot. The
      xenograft animal model was established by inoculation of HepG2 cells. Results
      showed that ectopic expression of HCV core protein induced EMT in L02 hepatocytes
      and HepG2 tumor cells by upregulating vimentin, Sanl1, and Snal2 expression and
      downregulating E-cadherin expression. Moreover, Core protein downregulated miR
      30c and miR-203a levels in L02 and HepG2 cells, but artificial expression of miR
      30c and miR-203a reversed Core protein-induced EMT. Further analysis showed that
      ectopic expression of HCV core protein stimulated cell proliferation, inhibited
      apoptosis, and increased cell migration, whereas artificial expression of miR-30c
      and miR-203a significantly reversed the role of Core protein in these cell
      functions in L02 and HepG2 cells. In the HepG2 xenograft tumor models, artificial
      expression of miR-30c and miR-203a inhibited EMT and tumor growth. Moreover, L02
      cells overexpressing Core protein can form tumors in nude mice. In HCC patients,
      HCV infection significantly shortened patients' survival time, and loss of miR
      30c and miR-203 expression correlated with poor survival. In conclusion, HCV core
      protein downregulates miR-30c and miR-203a expression, which results in
      activation of EMT in normal hepatocytes and HCC tumor cells. The Core protein
      activated-EMT is involved in the carcinogenesis and progression of HCC. Loss of
      miR-30c and miR-203a expression is a marker for the poor prognosis of HCC. 

PMID- 26210454
TI  - HDAC6 maintains mitochondrial connectivity under hypoxic stress by suppressing
      MARCH5/MITOL dependent MFN2 degradation.
AB  - Mitochondria undergo fusion and fission in response to various metabolic
      stresses. Growing evidences have suggested that the morphological change of
      mitochondria by fusion and fission plays a critical role in protecting
      mitochondria from metabolic stresses. Here, we showed that hypoxia treatment
      could induce interaction between HDAC6 and MFN2, thus protecting mitochondrial
      connectivity. Mechanistically, we demonstrated that a mitochondrial ubiquitin
      ligase MARCH5/MITOL was responsible for hypoxia-induced MFN2 degradation in HDAC6
      deficient cells. Notably, genetic abolition of HDAC6 in amyotrophic lateral
      sclerosis model mice showed MFN2 degradation with MARCH5 induction. Our results
      indicate that HDAC6 is a critical regulator of MFN2 degradation by MARCH5, thus
      protecting mitochondrial connectivity from hypoxic stress. 

PMID- 26210455
TI  - Colchicine toxicity: an exaggerated reality?

PMID- 26210456
TI  - The reply.

PMID- 26210457
TI  - Why the physical examination gets no respect.

PMID- 26210458
TI  - The reply.

PMID- 26210459
TI  - Prevalence of comorbidities in patients with Takotsubo syndrome.

PMID- 26210460
TI  - The reply.

PMID- 26210461
TI  - Mostly early invasive management may improve outcomes in patients with myocardial
      infarction and cardiogenic shock.

PMID- 26210462
TI  - The reply.

PMID- 26210463
TI  - The good, the bad, and the...empathic.

PMID- 26210464
TI  - The reply.

PMID- 26210465
TI  - Atrial electrical activity: absent or scarcely evident?

PMID- 26210466
TI  - A microfluidic device for the automated electrical readout of low-density glass
      slide microarrays.
AB  - Microarrays are a powerful platform for rapid and multiplexed analysis in a wide
      range of research fields. Electrical readout systems have emerged as an
      alternative to conventional optical methods for microarray analysis thanks to its
      potential advantages like low-cost, low-power and easy miniaturization of the
      required instrumentation. In this work an automated electrical readout system for
      low-cost glass-slide microarrays is described. The system enables the
      simultaneous conductimetric detection of up to 36 biorecognition events by
      incorporating an array of interdigitated electrode transducers. A
      polydimethylsiloxane microfluidic structure has been designed that creates
      microwells over the transducers and incorporates the microfluidic channels
      required for filling and draining them with readout and cleaning solutions, thus
      making the readout process fully automated. Since the capture biomolecules are
      not immobilized on the transducer surface this readout system is reusable, in
      contrast to previously reported electrochemical microarrays. A low-density
      microarray based on a competitive enzymatic immunoassay for atrazine detection
      was used to test the performance of the readout system. The electrical assay
      shows a detection limit of 0.22+/-0.03 MUg L(-1) similar to that obtained with
      fluorescent detection and allows the direct determination of the pesticide in
      polluted water samples. These results proved that an electrical readout system
      such as the one presented in this work is a reliable and cost-effective
      alternative to fluorescence scanners for the analysis of low-density microarrays.

PMID- 26210467
TI  - Real-time fluorescence ligase chain reaction for sensitive detection of single
      nucleotide polymorphism based on fluorescence resonance energy transfer.
AB  - Most of practical methods for detection of single nucleotide polymorphism (SNP)
      need at least two steps: amplification (usually by PCR) and detection of SNP by
      using the amplification products. Ligase chain reaction (LCR) can integrate the
      amplification and allele discrimination in one step. However, the detection of
      LCR products still remains a great challenge for highly sensitive and
      quantitative SNP detection. Herein, a simple but robust strategy for real-time
      fluorescence LCR has been developed for highly sensitive and quantitative SNP
      detection. A pair of LCR probes are firstly labeled with a fluorophore and a
      quencher, respectively. When the pair of LCR probes are ligated in LCR, the
      fluorophore will be brought close to the quencher, and thus, the fluorescence
      will be specifically quenched by fluorescence resonance energy transfer (FRET).
      The decrease of fluorescence intensity resulted from FRET can be real-time
      monitored in the LCR process. With the proposed real-time fluorescence LCR assay,
      10 aM DNA targets or 100 pg genomic DNA can be accurately determined and as low
      as 0.1% mutant DNA can be detected in the presence of a large excess of wild-type
      DNA, indicating the high sensitivity and specificity. The real-time measuring
      does not require the detection step after LCR and gives a wide dynamic range for
      detection of DNA targets (from 10 aM to 1 pM). As LCR has been widely used for
      detection of SNP, DNA methylation, mRNA and microRNA, the real-time fluorescence
      LCR assay shows great potential for various genetic analysis.

PMID- 26210468
TI  - QCM sensing of melphalan via electropolymerized molecularly imprinted
      polythiophene films.
AB  - A sensor for the determination of melphalan (mel) using 3-thiophene acetic acid
      (3-TAA) as functional monomer was fabricated by electropolymerization on gold
      surface. The polymeric film was formed on the surface of gold electrode as well
      as on gold-coated electrochemical quartz crystal microbalance (EQCM) electrode by
      electropolymerization of 3-TAA in presence of mel template by cyclic voltammetry
      (CV). Various parameters were optimized for controlling the performance of
      molecularly imprinted polymer (MIP) modified sensor such as ratio of monomer and
      template ratio, number of electropolymerization cycles, mass deposited in each
      cycle, pH, etc. The prepared MIP sensor was highly specific towards mel and the
      recognition was analyzed by both differential pulse voltammetry (DPV) and quartz
      crystal microbalance (QCM) to verify the changes in currents. In the optimal
      condition, response of MIP sensor to mel was linearly proportional to its
      concentration with limit of detection (LOD) as 5.40 ng mL(-1). Hence, a highly
      sensitive and selective piezoelectric sensor for mel has been reported here via
      imprinting approach for the first time.

PMID- 26210469
TI  - A "signal-on'' aptasensor for simultaneous detection of chloramphenicol and
      polychlorinated biphenyls using multi-metal ions encoded nanospherical brushes as
      tracers.
AB  - A "signal-on'' aptasensor was developed for simultaneous detection of
      chloramphenicols (CAP) and polychlorinated biphenyl-72 (PCB72) with a novel multi
      metal ions encoded nanospherical brushes as nanotracers. To construct the assay,
      the respective aptamer of CAP and PCB72 labeled magnetic gold nanoparticles as
      capture probes (aptamer-MGPs), and their complementary single strand DNA (s-DNA)
      encoded metal ions (Cd(2+) and Pb(2+)) on nanospherical branched polyethylene
      imine brushes as tracers (s-DNA-MSPEIs), were simultaneously synthesized. After
      that, the capture probe and tracers were connected through a hybridization
      reaction between s-DNA and aptamers. In the presence of CAP and PCB72, the
      analytes could react with the aptamers on capture probes and release the tracers
      into supernatant after magnetic separation. The released tracers with metal ions
      (Cd(2+) and Pb(2+)) could be simultaneously detected through the square wave
      voltammetry (SWV) without acid dissolution, which can switch the signals of the
      biosensor to "on'' state. Under optimal conditions, the assay could detect CAP
      and PCB72 as low as 0.3 pg mL(-1) with the dynamitic range from 0.001 to 100 ng
      mL(-1) and exhibited excellent selectivity. More importantly, the strategy can be
      extended easily to other targets after changing the corresponding aptamers and
      other metal ions tracers, which provides a promising and facile approach in
      multiplex detection of ultra-trace level of pollutants in food safety without
      more complex separation and washing steps.

PMID- 26210470
TI  - On-chip quantitative detection of pathogen genes by autonomous microfluidic PCR
      platform.
AB  - Polymerase chain reaction (PCR)-based genetic testing has become a routine part
      of clinical diagnoses and food testing. In these fields, rapid, easy-to-use, and
      cost-efficient PCR chips are expected to be appeared for providing such testing
      on-site. In this study, a new autonomous disposable plastic microfluidic PCR chip
      was created, and was utilized for quantitative detection of pathogenic
      microorganisms. To control the capillary flow of the following solution in the
      PCR microchannel, a driving microchannel was newly designed behind the PCR
      microchannel. This allowed the effective PCR by simply dropping the PCR solution
      onto the inlet without any external pumps. In order to achieve disposability,
      injection-molded cyclo-olefin polymer (COP) of a cost-competitive plastic was
      used for the PCR chip. We discovered that coating the microchannel walls with non
      ionic surfactant produced a suitable hydrophilic surface for driving the
      capillary flow through the 1250-mm long microchannel. As a result, quantitative
      real-time PCR with the lowest initial concentration of human, Escherichia coli
      (E. coli), and pathogenic E. coli O157 genomic DNA of 4, 0.0019, 0.031 pg/MUl,
      respectively, was successfully achieved in less than 18 min. Our results indicate
      that the platform presented in this study provided a rapid, easy-to-use, and low
      cost real-time PCR system that could be potentially used for on-site gene
      testing.

PMID- 26210471
TI  - Current trends in nanomaterial embedded field effect transistor-based biosensor.
AB  - Recently, as metal-, polymer-, and carbon-based biocompatible nanomaterials have
      been increasingly incorporated into biosensing applications, with various
      nanostructures having been used to increase the efficacy and sensitivity of most
      of the detecting devices, including field effect transistor (FET)-based devices.
      These nanomaterial-based methods also became the ideal for the amalgamation of
      biomolecules, especially for the fabrication of ultrasensitive, low-cost, and
      robust FET-based biosensors; these are categorically very successful at binding
      the target specified entities in the confined gated micro-region for high
      functionality. Furthermore, the contemplation of nanomaterial-based FET
      biosensors to various applications encompasses the desire for detection of many
      targets with high selectivity, and specificity. We assess how such devices have
      empowered the achievement of elevated biosensor performance in terms of high
      sensitivity, selectivity and low detection limits. We review the recent
      literature here to illustrate the diversity of FET-based biosensors, based on
      various kinds of nanomaterials in different applications and sum up that graphene
      or its assisted composite based FET devices are comparatively more efficient and
      sensitive with highest signal to noise ratio. Lastly, the future prospects and
      limitations of the field are also discussed. 

PMID- 26210472
TI  - Reconfigurable hybrid interface for molecular marker diagnostics and in-situ
      reporting.
AB  - Combinations of molecular signals such as transcription factors and microRNAs in
      cells are a reliable indicator of multi-gene disorders. A system capable of
      detecting these conditions in-situ may be used as a tool for diagnosis and
      monitoring of disease. Here, we engineer genetic circuits that sense endogenous
      levels of the androgen receptor (AR), the glucocorticoid receptor (GR), and the
      microRNA hsa-miR-21 (miR-21) in cervical cancer cells (HeLa). Furthermore, using
      the mediator molecule human chorionic gonadotropin (hCG), we interface the
      intracellular information to enzyme-linked immunosorbent assay (ELISA) test
      strips. We demonstrate that this hybrid genetic circuit and test-strip interface
      can accommodate combinatorial, low-cost, and in-situ reporting, a versatile
      profiling tool. 

PMID- 26210473
TI  - Bm59 is an early gene, but is unessential for the propagation and assembly of
      Bombyx mori nucleopolyhedrovirus.
AB  - Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen that specifically
      infects the domestic silkworm and causes serious economic loss to sericulture
      around the world. The function of BmNPV Bm59 gene in the viral life cycle is
      inconclusive. To investigate the role of Bm59 during viral infection, the
      transcription initiation site and temporal expression of Bm59 were analyzed, and
      Bm59-knockout virus was generated through homologous recombination in Escherichia
      coli. The results showed that Bm59 is an early transcription gene with an atypia
      early transcriptional start motif. Budded virion (BV) production and DNA
      replication in the BmN cells transfected with the Bm59-knockout virus bacmid were
      similar to those in the cells transfected with the wild-type virus. Electron
      microscopy revealed that the occlusion-derived virus can be produced in cells
      infected with the Bm59-knockout virus. These results indicated that Bm59 is an
      early gene and is not essential for viral replication or assembly of BmNPV. These
      findings suggested that non-essential gene (Bm59) remained in the viral genome,
      which may interact with other viral/host genes in a certain situation. 

PMID- 26210475
TI  - Sleep Apnea, Depression, and Sleep Problems: Inter-relationship in Patients with
      Severe Obstructive Sleep Apnea.

PMID- 26210474
TI  - Where is Noninvasive Ventilation Actually Delivered for Acute Respiratory
      Failure?
AB  - PURPOSE: Few studies have examined locations of noninvasive ventilation (NIV)
      application for acute respiratory failure (ARF). We aimed to track actual
      locations of NIV delivery and related outcomes. METHODS: Observational cohort
      study based at 8 acute care hospitals in Massachusetts on adult patients admitted
      for ARF requiring ventilatory support during pre-determined time intervals.
      RESULTS: Of 1225 ventilator starts, 499 were NIV; 209 (42%) in intensive care
      units (ICU), 185 (37%) in emergency departments (ED), 91 (18%) on general wards,
      and 14 (3%) in other units. Utilization (% of all ventilator starts) (1), success
      (2) and in-hospital mortality (3) rates for patients initiated on NIV in ICU, ED,
      and general and other wards were (1) 38, 36, 73, and 52%, (2) 60, 77, 68, and 93%
      and (3) 25, 12, 17, and 0%, respectively (p < 0.05 for all). Patients with acute
      on-chronic lung disease (ACLD) and acute pulmonary edema (APE) were begun on NIV
      most often in EDs and patients with 'de novo' ARF and neurologic disorders most
      often in ICU's. Approximately 2/3 of patients begun on NIV outside of ICUs were
      transferred within 72 h to ICUs, wards or other units. CONCLUSIONS: Most NIV
      starts occurred in ICUs and EDs but utilization rate was highest (>50%) on
      general wards where a fifth of NIV starts took place. Actual location depended on
      etiology of ARF as patients with ACLD and APE were started more often in EDs and
      "de novo" ARF in ICU. NIV failure and mortality rates were higher in ICUs related
      to the greater proportion of patients with "de novo" ARF.

PMID- 26210476
TI  - Placental Transmogrification of the Lung.

PMID- 26210477
TI  - Evaluation of CD4(+)CD25(+)FoxP3(+) T cell populations, IL-10 production, and
      their correlation with clinical and biochemical parameters in sickle cell anemia
      patients with leg ulcers.
AB  - Leg ulcers (LUs) are a debilitating complication of sickle cell anemia (SCA),
      with inflammation known to play a crucial role in their pathogenesis. Many
      studies have described the roles of T helper type 1 (Th1) and Th2 pathways in
      SCA; however, defects in anti-inflammatory responses are poorly understood. We
      evaluated interleukin (IL)-10 levels in serum and peripheral blood mononuclear
      cells (PBMCs) in SCA patients with leg ulcers (SCALU) and without leg ulcers
      (SCAWH) in addition to CD4(+) CD25(+)FoxP3(+) T cell populations and their its IL
      10 expression. In stimulated and unstimulated PBMC cultures, SCALU patients
      produced higher levels of IL-10 than those in the SCAWH group. Higher levels of
      IL-10 in SCALU patients correlated with a history of osteonecrosis in stimulated
      and unstimulated cultures when compared with those in SCAWH. Immunophenotyping
      revealed that SCALU patients had a higher proportion of CD4(+)CD25(+)FoxP3(+),
      Tr1 and CD4(+)CD25(+)FoxP3(+)IL-10(+) T cells than other groups. Our findings
      revealed that IL-10 levels were increased in unstimulated cells from the SCALU
      group, and that this group also presented with a predominant CD4(+)
      CD25(+)FoxP3(+) cell population despite many of those cells being IL-10 negative.

PMID- 26210478
TI  - Effect of added autochthonous yeasts on the volatile compounds of dry-cured hams.
AB  - Three yeast strains belonging to Debaryomyces and Hyphopichia spp., isolated from
      dry-cured hams and previously tested for biocontrol activity against toxigenic
      Penicillium nordicum, were investigated for ability in colonising ham surface.
      Hams were twice yeast-inoculated onto the unskinned muscle surface during
      ripening and processed up to full maturation in two manufacturing plants. The
      yeast strains and the manufacturing plants differed (P < 0.05) in surface
      populations, volatile compounds and sensory descriptors of matured hams. Sensory
      scores for each of the yeast-inoculated groups were higher or similar to the non
      inoculated ones (controls). Debaryomyces strains were regarded as those most fit
      to colonise the ham surface under the ecological conditions of dry-curing rooms,
      hence to qualify as biocontrol agents against the growth of undesired mould and
      preserve the typical sensory properties of dry-cured hams.

PMID- 26210479
TI  - Spinal neurenteric cysts: Associated developmental anomalies and rationale of
      surgical approaches.
AB  - BACKGROUND: Neurenteric cysts (NC) occur due to failure of separation of
      neurectoderm from endoderm at the 3rd week of embryogenesis. This study focuses
      on key clinico-radiological features of NCs, with emphasis on surgical nuances
      involved in resecting anteriorly placed NC, especially at the foramen magnum
      (FM). METHOD: Sixteen consecutive patients having a spinal NC were included.
      Their clinico-radiological status, surgical nuances and follow-up status were
      noted. RESULTS: The duration of spasticity/paraparesis/quadriparesis ranged from
      15 days to 48 months. Twelve patients had an intradural extramedullary (IDEM;
      nine anterior and three anterolateral) cyst and four had an intramedullary (IM)
      cyst. Six of them had an anteriorly placed FM lesion (five IDEM and one IM).
      Amongst ten subaxial NCs, four were anterior, two antero-lateral and one postero
      lateral; three were IM. Three patients had the characteristic stigmata of occult
      spinal dysraphism: two, a large mesenteric cyst, and one, a posterior mediastinal
      cyst. Excision was total in 13 patients. Subtotal excision of tumour capsule was
      performed for two recurrent cysts and an IM cyst. A far lateral approach was
      adopted for anteriorly placed FM lesions and posterior laminectomy for subaxial
      lesions. Histopathology revealed eight type A cysts, four type B cysts and four
      type C cysts. At follow-up (range, 8 months to 12 years; median, 60 +/- 45.84
      months), complete neurological recovery occurred in seven patients; six patients
      had persistent spasticity but only minor disability; two patients had difficulty
      in walking; and one patient with an anteriorly placed thoracic recurrent NC had
      sustained neurological deterioration. CONCLUSIONS: Surgical difficulties in
      addressing NCs are related to their anterior or IM location, presence of
      adhesions and inability to dissect the tumour capsule from the spinal cord due to
      fibrous or lipomatous connections. The associated developmental anomalies must be
      specifically sought and addressed.

PMID- 26210480
TI  - Retrospective feasibility analysis of modified posterior partial vertebrectomy
      with 360-degree decompression in destructive thoracic spondylodiscitis.
AB  - BACKGROUND: Advanced states of vertebral osteomyelitis accompanied by spinal
      instability, epidural abscess formation, and neurological deficits require
      surgical decompression, stabilization, and often reconstruction of the anterior
      and posterior columns. The efficacy of a posterolateral approach with resection
      of inflammatory tissue, and interbody (titanium cages) and dorsal fusion was
      investigated and the clinical and radiological parameters (correction of kyphosis
      and fusion rates) were evaluated. METHOD: From 2011 to 2014, ten consecutive
      patients were treated at our institution using the modified technique of a
      transversecomy without costal resection to decompress neural structures and
      resect inflammatory tissue in destructive thoracic vertebral osteomyelitis.
      Flattening of the endplates without complete corpectomy, 360-degree
      stabilization, and correction of kyphosis by posterior shortening instead of
      anterior distraction were performed to avoid an additional ventral approach.
      Clinical and radiological data were retrospectively analyzed. RESULTS: All ten
      patients (six male and four female, mean age, 66 years) suffered from severe and
      destructive osteomyelitis. Surgery was performed successfully in all ten
      patients. Mean surgical time was 308 min. Mean follow-up was 19 months (range, 2
      32 months). Neither approach-related or pulmonary complications nor recurrence of
      osteomyelitis were observed. All patients experienced pain relief after the
      procedure (mean back pain VAS was 8.8 pre-treatment and 3.2 at the final follow
      up). Fusion was observed in all patients on the basis of computerized tomography
      scans. The mean radiological segmental kyphosis was corrected from 20 degrees 
      preoperatively to 7 degrees  after surgery and 9 degrees  at the final follow-up.
      CONCLUSIONS: The modified posterior transversectomy with 360-degree decompression
      and anterior wall reconstruction with titanium cages in combination with
      posterior instrumentation for sagittal alignment correction is a reliable,
      effective, and safe treatment option.

PMID- 26210481
TI  - Hemorrhage in cavum septum pellucidum et vergae: it does exist!

PMID- 26210482
TI  - Rosai-Dorfman disease involving the central nervous system: seven cases from one
      institute.
AB  - BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, idiopathic, non-neoplastic
      histioproliferative disease. Central nervous system (CNS) manifestations are
      extremely rare. Its low incidence and unknown etiology restrict early diagnosis
      and optimal therapy. METHODS: In the 1995-2013 period, seven CNS-RDD patients
      with intracranial and/or spinal lesions were retrospectively analyzed, including
      the clinical data, laboratory and imaging results, treatment applied and outcome.
      All seven case samples were screened for the SLC29A3 gene mutation, and the
      literature was reviewed. RESULTS: Seven RDD patients (6 male/1 female, aged
      between 7 and 68) with CNS manifestations are reported. Five of the seven
      patients (71.4 %) had intracranial lesions (1 with skull erosion and 1 with
      multiple lesions mimicking meningiomas), and two (28.6 %) had spinal subdural
      lesions. The patients' symptoms included headaches, seizures, visual loss,
      epileptoid convulsions in the lower legs, fever, spastic paraparesis and
      paraplegia. An elevated erythrocyte sedimentation rate (ESR) was detected in five
      of the seven cases. The diagnosis was confirmed by immunohistochemical staining
      revealing that the characteristic histiocytes were positive for the S100 protein
      and CD68 and negative for CD1a. All patients were operated on: three recovered
      completely, two were partially rehabilitated, and two died. No SLC29A3 gene
      mutations were found in any of the seven samples. CONCLUSION: This short series
      suggests the following: (1) RDD should be included in the differential diagnosis
      of lesions mimicking intracranial/spinal meningiomas or inflammatory lesions,
      especially in children; (2) the definitive diagnosis is based on histopathology
      and immunocytochemistry; (3) surgical resection seems to be the most effective
      therapy; (4) the exact etiology and adjuvant therapy for relapsing/incompletely
      resected lesions remain to be established.

PMID- 26210483
TI  - Ex Vivo Evaluation of the Accuracy of Electronic Foramen Locators in Root Canals
      with an Obstructed Apical Foramen.
AB  - INTRODUCTION: The objective of the present study was to evaluate the accuracy of
      electronic foramen locators (EFLs), Root ZX II (RZX; J. Morita, Tokyo, Japan),
      Propex II (Dentsply Maillefer, Ballaigues, Switzerland), and Apex ID (AID;
      SybronEndo, Glendora, CA), in root canals with an obstructed apical foramen (OAF)
      and to compare them with those 1.0 mm short of the apical foramen (AF; -1.0) and
      at the AF (0.0). METHODS: Thirty human mandibular molars had their coronal and
      cervical preparations accessed. Then, the AFs were standardized (250 MUm).
      Electronic root canal measurements were performed for the -1.0 and 0.0 working
      lengths, and the canals were obstructed with dentinal debris. The distance to the
      AF displayed by the EFLs was then recorded. The last instrument used was fixed
      with a cyanoacrylate-based adhesive; the apical portions of the roots were
      scraped, allowing for the determination of the distance between the tips of the
      instruments and the AFs. RESULTS: The precision rates at 0.0, -1.0, and the OAF
      were 94.7%, 43.9%, and 1.8% (RZX); 93.0%, 54.4%, and 54.4% (Propex II); and
      93.0%, 68.5%, and 75.4% (AID), respectively (+/-0.5 mm). No significant
      differences were found between the devices at 0.0; however, for the measurements
      at -1.0 and the OAF, the AID offered significantly better results than RZX (P <
      .05). CONCLUSIONS: The absence of foraminal patency caused by dentin debris
      obstruction affects the accuracy of the EFLs differently, suggesting distinctive
      interactions with their operating mechanisms.

PMID- 26210484
TI  - The promises of neurodegenerative disease modeling.
AB  - The rise in the prevalence of neurodegenerative diseases parallels the rapid
      increase in human lifespan. Despite intensive research, the molecular and
      cellular mechanisms underlying the onset and progression of these devastating
      diseases with age are still poorly understood. Many aspects of these diseases
      have been modelled successfully in experimental animals such as the mouse, the
      zebrafish Brachydanio rero, the nematode worm Caenorhaditis elegans and the fruit
      fly Drosophila melanogaster. This review will focus on the advantages offered by
      the genetic tools available in Drosophila for combining powerful strategies in
      order to tackle the causative factors of these complex pathologies and help to
      elaborate efficient drugs to treat them. 

PMID- 26210485
TI  - [A new classification for better care. The promises of the translational
      psychiatric neuroscience].
AB  - This article explores the way neuroscientists call for the "deconstruction" of
      the classifications of mental disorders as we know them, in order to provide
      solutions to the slowdown of therapeutical innovation in psychiatry. It is based
      on the case study of the Research Domain Criteria (RDoC) project of the US
      National Institute of Mental Health (NIMH). My purpose is to show that
      neuroscience interested in mental disorders offers narratives of innovation,
      transformation, and desirable futures that are at the heart of the ambitious
      current research projects and influence them. I approach the versions of the
      futures proposed by the promoters of translational psychiatric neuroscience in
      terms of productivity at the scientific, epistemological and socio-political
      levels. 

PMID- 26210486
TI  - Inhibitory effect of iron withdrawal by chelation on the growth of human and
      murine mammary carcinoma and fibrosarcoma cells.
AB  - Since iron uptake is essential for cell growth, rapidly dividing cancer cells are
      sensitive to iron depletion. To explore the effect of iron withdrawal on cancer
      cell growth, mouse and human mammary carcinoma cells (4T1 and MDA-MB-468,
      respectively) and mouse and human fibrosarcoma cells (L929 and HT1080,
      respectively) were cultured in the absence or presence of DIBI, a novel iron
      chelating polymer containing hydroxypyridinone iron-ligand functionality. Cell
      growth was measured by a colorimetric assay for cell metabolic activity. DIBI
      treated 4T1, MDA-MB-468, L929 and HT1080 cells, as well as their normal
      counterparts, showed a dose- and time-dependent reduction in growth that was
      selective for human cancer cells and mouse fibrosarcoma cells. The inhibitory
      effect of DIBI on fibrosarcoma and mammary carcinoma cell growth was reversed by
      addition of exogenous iron in the form of iron (III) citrate, confirming the iron
      selectivity of DIBI and that its inhibitory activity was iron-related.
      Fibrosarcoma and mammary carcinoma cell growth inhibition by DIBI was associated
      with S-phase cell cycle arrest and low to moderate levels of cell death by
      apoptosis. Consistent with apoptosis induction following DIBI-mediated iron
      withdrawal, fibrosarcoma and mammary carcinoma cells exhibited mitochondrial
      membrane permeabilization. A comparison of DIBI to other iron chelators showed
      that DIBI was superior to deferiprone and similar to or better than deferoxamine
      for inhibition of fibrosarcoma and mammary carcinoma cell growth. These findings
      suggest that iron withdrawal from the tumor microenvironment with a selective and
      potent iron chelator such as DIBI may prevent or inhibit tumor progression. 

PMID- 26210488
TI  - 2014 G.J. Schroepfer Jr. Memorial AOCS Sterol Symposium: Recent Advances in
      Sterol Research.

PMID- 26210487
TI  - Advanced glycation end products accelerate arteriosclerosis after renal
      transplantation through the AGE/RAGE/ILK pathway.
AB  - BACKGROUND: The effects of advanced glycation end products (AGEs) on
      arteriosclerosis (AS) after kidney transplantation and the molecular mechanisms
      involved remain unclear. METHODS: Samples were collected from 30 healthy
      volunteers and 30 renal transplant recipients (RTRs) to determine the levels of
      AGEs and to observe both histological changes and alpha-smooth muscle actin
      (alpha-SMA) and osteopontin (OPN) expression. Furthermore, we analyzed alpha-SMA,
      OPN and integrin-linked kinase (ILK) in rat vascular smooth muscle cells (VSMCs)
      that were treated with AGEs and in ILK plasmid transfected rat VSMCs treated with
      AGEs. Finally, we measured the expression of ILK and the receptor for advanced
      glycation end (RAGE) products in rat VSMCs treated with AGEs and an anti-RAGE
      antibody. RESULTS: Significant differences in the histological changes, serum
      AGEs, and expression of alpha-SMA and OPN in arterial walls were noted between
      healthy volunteers and RTRs. Significant OPN and ILK overexpression and reduced
      alpha-SMA expression were detected in a time-dependent manner in rat VSMCs after
      treatment with AGEs. Similar outcomes were observed regarding the overexpression
      of ILK, and these results could be prevented via RAGE inhibition. CONCLUSIONS:
      AGEs may play a critical role in the formation and progression of AS after renal
      transplantation by inducing VSMCs-to-osteoblast trans-differentiation through the
      AGE/RAGE/ILK pathway.

PMID- 26210490
TI  - Volumetric analysis of the initial index computed tomography scan can predict the
      natural history of acute uncomplicated type B dissections.
AB  - OBJECTIVE: Our objective was to characterize the predictive impact of computed
      tomography (CT) scan volumetric analysis on the natural history of acute
      uncomplicated type B aortic dissections (ADs). METHODS: We conducted a
      retrospective review of patients with acute type B ADs from 2009 to 2014. On an
      iNtuition workstation (TeraRecon, Foster City, Calif), volume measurements were
      obtained using the true lumen volume (TLV), false lumen volume (FLV), and total
      aortic volume from the left subclavian artery to the celiac artery. Growth rate
      was calculated as the change in maximal diameter between first and last available
      CT scans during the time interval. The primary outcome of the study was delayed
      aortic intervention. P < .05 was considered statistically significant. RESULTS:
      During a 5-year period, 164 patients had CT scan evidence of acute type B ADs; 11
      patients were excluded for lack of subsequent follow-up imaging; 36 patients who
      underwent urgent repair (<14 days from presentation) were also excluded. We
      evaluated a total of 117 patients: 85 patients who did not require intervention
      and 32 who underwent delayed (>14 days) thoracic endovascular aneurysm repair
      (29) or open repair (3). Mean age was 66 +/- 12 years. Mean TLV/FLV ratio on
      initial CT scan was significantly higher in patients who did not eventually
      require an operation (1.55 vs 0.82; P = .02). The mean growth rate was higher in
      those eventually requiring operation (2.47 vs 0.42 mm/mo; P = .003). Patients
      were divided into three subgroups on the basis of their initial imaging TLV/FLV
      ratios (<0.8, 0.8-1.6, and >1.6). There was a significant difference in the
      growth rates between these three groups (4.6 vs 2.4 vs 0.8 mm/mo; P < .025). Area
      under the receiver operating characteristic curve analysis revealed that a
      TLV/FLV ratio <0.8 was highly predictive for requiring an intervention (area =
      0.8; sensitivity, 69%; specificity, 84%: positive predictive value, 71%; negative
      predictive value, 81%), with an odds ratio of 12.2 (confidence interval, 5-26; P
      < .001). Conversely, a TLV/FLV ratio of >1.6 was highly predictive for freedom
      from delayed operation (sensitivity, 91%; specificity, 42%; positive predictive
      value, 61%; negative predictive value, 86%). After Kaplan-Meier analysis, 1-year
      and 2-year survival free of aortic interventions was 60% and 42% with a TLV/FLV
      ratio <0.8 and 92% and 82% with a ratio >1.6 (P = .001). CONCLUSIONS: Initial CT
      scan volumetric analysis in patients presenting with uncomplicated acute type B
      ADs is a useful tool to predict growth and need for future intervention.

PMID- 26210489
TI  - Natural Rumen-Derived trans Fatty Acids Are Associated with Metabolic Markers of
      Cardiac Health.
AB  - Evidence suggests that industrial trans fatty acids (iTFA) impair lipid profiles
      while ruminant trans fatty acids (rTFA) may lower insulin resistance and blood
      pressure. The objective of this article was to determine if the plasma
      phospholipid percentage of rTFA is associated with a favorable cardiometabolic
      profile. We collected fasting blood samples from 200 individuals from Quebec city
      (QC, Canada) aged from 18 to 55 years old, including 100 obese (BMI >= 30 kg m(
      2)) and 100 non-obese (BMI < 30 kg m(-2)) men and women. Fatty acid levels in
      plasma phospholipids were determined using gas chromatography. After separating
      the subjects into two groups, according to the median percentage of rTFA in
      plasma phospholipids, participants in the group with higher percentages of rTFA
      (0.86 +/- 0.24 %) had higher adiponectin levels (p = 0.01) and a lower blood
      pressure (systolic, p = 0.005; diastolic, p = 0.04). In contrast, concentrations
      in plasma phospholipids of elaidic acid, a major iTFA, are positively correlated
      with glycemia in non-obese subjects (p = 0.01) and with both triacylglycerol
      (TAG) (p = 0.0007) and total cholesterol (TC) (p = 0.009) in obese subjects.
      These data suggest that rTFA may have beneficial effects on cardiometabolic risk
      factors conversely to their counterpart iTFA. Dietary sources of TFA should be
      taken into account in future cardiometabolic studies.

PMID- 26210491
TI  - The first assessment of operative logs for traditional vascular fellowship track
      versus integrated vascular training programs.
AB  - OBJECTIVE: As vascular surgery training paradigms evolve, one measure of success
      is operative experience. This study assessed the initial operative experience of
      those graduating from new integrated programs (0+5) vs those from the traditional
      programs (5+2). METHODS: National operative case log data supplied by the
      Accreditation Council for Graduate Medical Education was compiled for vascular
      surgical residents graduating between 2010 and 2013. Mean case numbers for the
      0+5 residents were compared with those for the 5+2 residents (experience from
      their general surgery residency plus vascular fellowship) for total vascular
      operations, open vascular operations, endovascular procedures, and total
      operative experience. RESULTS: The 5+2 trainees performed significantly more
      procedures than the 0+5 trainees (mean, 1605 vs 1015); however, they performed
      12% less vascular procedures (mean, 758 vs 851). No significant differences in
      total number of open vascular operations (mean, 404 vs 411) or specific open
      operations for cerebral vascular disease, aneurysm, peripheral obstruction, and
      access were found. The increase in vascular procedures logged by 0+5 trainees was
      realized by a 24% increase in endovascular procedures, mainly involving
      diagnostic arteriography, caval filter placement, and balloon angioplasty. No
      significant differences were seen in endovascular aneurysm repair (mean, 63 vs
      60) and stent placement (mean, 59 vs 60). CONCLUSIONS: This report summarizes the
      first data available for the 0+5 trainee operative experience. Compared with the
      traditional 5+2 trainees, the 0+5 trainees have (1) equivalent open vascular
      training and (2) overall superior endovascular training, although this was
      accounted via an increase in minor procedures. The overall operative experience
      remains greater for the 5+2 trainees secondary to 2 extra years of training.
      Further longitudinal studies will be needed to fully characterize the effect of
      the new 0+5 training paradigm.

PMID- 26210492
TI  - Discussion.

PMID- 26210493
TI  - Pediatric giant cell tumor of the tendon sheath of the craniocervical junction
      involving the occipital condyle.
AB  - INTRODUCTION: Giant cell tumor of the tendon sheath (GCTTS), also called
      pigmented villonodular synovitis, is a common lesion of the synovial membrane of
      the hand joint, but it uncommonly involves the axial skeleton, especially in
      pediatric populations. Furthermore, GCTTS originating from the occipital condyle
      has not been reported previously. CASE REPORT: A 15-year-old girl presented with
      a palpable neck mass for 1 year, and imaging studies revealed a less demarcated
      and heterogeneously enhanced mass in the suboccipital region. The tumor was
      originating from the occipital condyle that eroded the skull and atlas, and it
      was completely resected via a far lateral transcondylar approach followed by
      transarticular screw fixation. After the resection, we performed occipitocervical
      fusion to prevent spinal instability. The patient made an uneventful recovery
      after surgery. Recurrence has not been observed after 5 years of follow-up.
      DISCUSSION: We report this rare case and briefly review the general features and
      unusual locations of GCTTS with recommendations for treatment modalities.

PMID- 26210494
TI  - Cervical intervertebral disc calcification combined with ossification of
      posterior longitudinal ligament in an-11-year old girl: case report and review of
      literature.
AB  - To present the clinical feature, radiographic characteristic, treatment and
      prognosis of an 11 years old girl with cervical intervertebral disc calcification
      combined with ossification of posterior longitudinal ligament(OPLL). BACKGROUND:
      Calcification is the degeneration of intervertebral disc, mostly occurs in the
      cervical segment. The pediatric cervical intervertebral disc calcification
      associated with OPLL is very rare. The etiology and treatment guidelines of this
      complex are poorly known. METHOD: An 11 years old girl experienced neck pain for
      3 months,aggravated for half a month. Neurological examination revealed the
      limitation of cervical spine motion and numbness of the upper left extremity. The
      spine radiograph, computed tomography and magnetic resonance imaging confirmed
      the diagnosis of cervical intervertebral disc calcification accompanied with
      OPLL. Conservative intervention was performed, followed up with an observation
      for 6 months. RESULT: On admission, the spine radiograph and computed tomography
      found the calcified intervertebral disc of C5/6 and ossified posterior
      longitudinal ligament at C5/6,C6 level, leading to spinal canal stenosis and
      spine cord compression. After a two-week in-hospital conservative treatment, the
      patient's neurologic symptoms were relieved. Two months later, the computed
      tomography confirmed the calcification of C5/6 intervertebral disc and ossified
      mass decreased significantly, spinal stenosis subsided. Six months later, the
      patient felt no discomfort, the computed tomography showed the ossified mass
      completely disappeared, only a small calcification remained at C5/6
      intervertebral disc. CONCLUSION: Intervertebral disc calcification associated
      with OPLL is extremely rare in children. In this case, OPLL is a temporary
      condition highly related to the disease process of Intervertebral disc
      calcification. The patient has a satisfactory recovery after non-surgical
      intervention. Conservative treatment is a prospective choice.

PMID- 26210495
TI  - Parasite transmission through suspension feeding.
AB  - Suspension-feeding bivalve molluscs are confronted with a wide range of materials
      in the benthic marine environment. These materials include various sized plankton
      and the organic material derived from it, macroalgae, detritus and a diversity of
      microbial parasites that have adapted life stages to survive in the water column.
      For bivalve parasites to infect hosts though, they must first survive and remain
      infectious in the water column to make initial contact with hosts, and once in
      contact, enter and overcome elaborate pathways for particle sorting and
      selection. Even past these defenses, bivalve parasites are challenged with
      efficient systems of mechanical and chemical digestion and highly evolved systems
      of innate immunity. Here we review how bivalve parasites evade these hurdles to
      complete their life cycles and establish within bivalve hosts. We broadly cover
      significant viral, bacterial, and protozoan parasites of marine bivalve molluscs,
      and illustrate the emergent properties of these host-parasite systems where
      parasite transmission occurs through suspension feeding. 

PMID- 26210496
TI  - Bacterial diseases in marine bivalves.
AB  - Bivalve aquaculture is seriously affected by many bacterial pathogens that cause
      high losses in hatcheries as well as in natural beds. A number of Vibrio species,
      but also members of the genera Nocardia and Roseovarius, are considered important
      pathogens in aquaculture. The present work provides an updated overview of main
      diseases and implicated bacterial species affecting bivalves. This review focuses
      on aetiological agents, their diversity and virulence factors, the diagnostic
      methods available as well as information on the dynamics of the host-parasite
      relationship. 

PMID- 26210497
TI  - Mass mortality in bivalves and the intricate case of the Pacific oyster,
      Crassostrea gigas.
AB  - Massive mortality outbreaks in cultured bivalves have been reported worldwide and
      they have been associated with infection by a range of viral and bacterial
      pathogens. Due to their economic and social impact, these episodes constitute a
      particularly sensitive issue in Pacific oyster (Crassostrea gigas) production.
      Since 2008, mortality outbreaks affecting C. gigas have increased in terms of
      intensity and geographic distribution. Epidemiologic surveys have lead to the
      incrimination of pathogens, specifically OsHV-1 and bacteria of the Vibrio genus,
      in particular Vibrio aestuarianus. Pathogen diversity may partially account for
      the variability in the outcome of infections. Host factors (age, reproductive
      status...) including their genetic background that has an impact on host
      susceptibility toward infection, also play a role herein. Finally, environmental
      factors have significant effects on the pathogens themselves, on the host and on
      the host-pathogen interaction. Further knowledge on pathogen diversity,
      classification, and spread, may contribute toward a better understanding of this
      issue and potential ways to mitigate the impact of these outbreaks.

PMID- 26210498
TI  - Lymphocyte-specific protein tyrosine kinase (Lck) interacts with CR6-interacting
      factor 1 (CRIF1) in mitochondria to repress oxidative phosphorylation.
AB  - BACKGROUND: Many cancer cells exhibit reduced mitochondrial respiration as part
      of metabolic reprogramming to support tumor growth. Mitochondrial localization of
      several protein tyrosine kinases is linked to this characteristic metabolic shift
      in solid tumors, but remains largely unknown in blood cancer. Lymphocyte-specific
      protein tyrosine kinase (Lck) is a key T-cell kinase and widely implicated in
      blood malignancies. The purpose of our study is to determine whether and how Lck
      contributes to metabolic shift in T-cell leukemia through mitochondrial
      localization. METHODS: We compared the human leukemic T-cell line Jurkat with its
      Lck-deficient derivative Jcam cell line. Differences in mitochondrial respiration
      were measured by the levels of mitochondrial membrane potential, oxygen
      consumption, and mitochondrial superoxide. Detailed mitochondrial structure was
      visualized by transmission electron microscopy. Lck localization was evaluated by
      subcellular fractionation and confocal microscopy. Proteomic analysis was
      performed to identify proteins co-precipitated with Lck in leukemic T-cells.
      Protein interaction was validated by biochemical co-precipitation and confocal
      microscopy, followed by in situ proximity ligation assay microscopy to confirm
      close-range (<16 nm) interaction. RESULTS: Jurkat cells have abnormal
      mitochondrial structure and reduced levels of mitochondrial respiration, which is
      associated with the presence of mitochondrial Lck and lower levels of
      mitochondrion-encoded electron transport chain proteins. Proteomics identified
      CR6-interacting factor 1 (CRIF1) as the novel Lck-interacting protein. Lck
      association with CRIF1 in Jurkat mitochondria was confirmed biochemically and by
      microscopy, but did not lead to CRIF1 tyrosine phosphorylation. Consistent with
      the role of CRIF1 in functional mitoribosome, shRNA-mediated silencing of CRIF1
      in Jcam resulted in mitochondrial dysfunction similar to that observed in Jurkat.
      Reduced interaction between CRIF1 and Tid1, another key component of
      intramitochondrial translational machinery, in Jurkat further supports the role
      of mitochondrial Lck as a negative regulator of CRIF1 through competitive
      binding. CONCLUSIONS: This is the first report demonstrating the role of
      mitochondrial Lck in metabolic reprogramming of leukemic cells. Mechanistically,
      it is distinct from other reported mitochondrial protein tyrosine kinases. In a
      kinase-independent manner, mitochondrial Lck interferes with mitochondrial
      translational machinery through competitive binding to CRIF1. These findings may
      reveal novel approaches in cancer therapy by targeting cancer cell metabolism.

PMID- 26210499
TI  - Implementation of improvement strategies in palliative care: an integrative
      review.
AB  - BACKGROUND: The European population is ageing, and as a consequence, an
      increasing number of patients are in need of palliative care, including those
      with dementia. Although a growing number of new insights and best practices in
      palliative care have been published, they are often not implemented in daily
      practice. The aim of this integrative review is to provide an overview of
      implementation strategies that have been used to improve the organisation of
      palliative care. METHODS: Using an integrative literature review, we evaluated
      publications with strategies to improve the organisation of palliative care.
      Qualitative analysis of the included studies involved categorisation of the
      implementation strategies into subgroups, according to the type of implementation
      strategy. RESULTS: From the 2379 publications identified, 68 studies with an
      experimental or quasi-experimental design were included. These studies described
      improvements using educational strategies (n = 14), process mapping (n = 1),
      feedback (n = 1), multidisciplinary meetings (n = 1) and multi-faceted
      implementation strategies (n = 51). Fifty-three studies reported positive
      outcomes, 11 studies reported mixed effects and four studies showed a limited
      effect (two educational and two multi-faceted strategies). CONCLUSIONS: This
      review is one of the first to provide an overview of the available literature in
      relation to strategies used to improve the organisation of palliative care. Since
      most studies reported positive results, further research is needed to identify
      and improve the effects of strategies aiming to improve the organisation of
      palliative care.

PMID- 26210501
TI  - Colonic neoplasms, an exceptional possibility in a coloplasty.

PMID- 26210500
TI  - CD4+ T cells in aged or thymectomized recipients of allogeneic stem cell
      transplantations.
AB  - BACKGROUND: CD4+CD25highFOXP3+ regulatory T (Treg) cells, which include thymus
      derived and peripherally induced cells, play a central role in immune regulation,
      and are therefore crucial to prevent graft-versus-host disease (GVHD). The
      increasing use of allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      for elderly patients with thymus regression, and our case of allo-HSCT shortly
      after total thymectomy, raised questions about the activity of thymus-derived
      Treg cells and peripherally induced Treg cells, which are otherwise
      indistinguishable. RESULTS: We found that despite pre-transplant thymectomy or
      older age, both naive and effector Treg cells, as well as naive and effector
      conventional T cells, proliferated in allo-HSCT recipients. Higher proportions of
      total Treg cells 1 month post allo-HSCT, and naive Treg cells 1 year post allo
      HSCT, appeared in patients achieving complete chimera without developing
      significant chronic GVHD, including our thymectomized patient, compared with
      patients who developed chronic GVHD. CONCLUSIONS: Treg cells that modulate human
      allogeneic immunity may arise peripherally as well as in the thymus of allo-HSCT
      recipients.

PMID- 26210502
TI  - Hepatic and intestine alterations in mice after prolonged exposure to low oral
      doses of Microcystin-LR.
AB  - Oral intake of Microcystin-LR (MC-LR) is the principal route of exposure to this
      toxin, with prolonged exposure leading to liver damage of unspecific
      symptomatology. The aim of the present paper was therefore to investigate the
      liver and intestine damage generated by prolonged oral exposure to low MC-LR
      doses (50 and 100 MUg MC-LR/kg body weight, administrated every 48 h during a
      month) in a murine model. We found alterations in TBARS, SOD activity and
      glutathione content in liver and intestine of mice exposed to both doses of MC
      LR. Furthermore, the presence of MC-LR was detected in both organs. We also found
      hepatic steatosis (3.6 +/- 0.6% and 15.3 +/- 1.6%) and a decrease in
      intraepithelial lymphocytes (28.7 +/- 5.0% and 44.2 +/- 8.7%) in intestine of 50-
      and 100-MUg MC-LR/kg treated animals, respectively. This result could have
      important implications for mucosal immunity, since intraepithelial lymphocytes
      are the principal effectors of this system. Our results indicate that prolonged
      oral exposure at 50 MUg MC-LR/kg every 48 h generates significant damage not only
      in liver but also in intestine. This finding calls for a re-appraisal of the
      currently accepted NOAEL (No Observed Adverse Effect Level), 40 MUg MC-LR/kg body
      weight, used to derive the guideline value for MC-LR in drinking water.

PMID- 26210503
TI  - Roger C. Woledge 1938-2015.

PMID- 26210504
TI  - Autopsy case of undiagnosed gangliocytoma in the medulla oblongata complicated
      with cerebral palsy.
AB  - A Japanese man in his 30s who had congenital cerebral palsy was found
      unresponsive in bed. His death was confirmed after resuscitation attempts. He had
      a history of occasional falling (despite the use of walking sticks and a
      wheelchair) owing to a slowly progressive gait disturbance, and had a medical
      examination without full neurological re-examination. Autopsy revealed
      gangliocytoma in the medulla oblongata, which was diagnosed as the cause of
      death. Although gangliocytoma is a well-differentiated benign tumor, the almost
      total replacement of the medulla oblongata by the tumor cells was assumed to
      result in ataxia via the olivocerebellar tract and secondary cerebellar atrophy,
      followed by central hypoventilation and death of the patient. The symptoms caused
      by gangliocytoma may be overlooked owing to long-standing cerebral palsy. 

PMID- 26210506
TI  - Structure-kinetics relationships of Capadenoson derivatives as adenosine A1
      receptor agonists.
AB  - We report the synthesis and biological evaluation of new derivatives of
      Capadenoson, a former drug candidate that was previously advanced to phase IIa
      clinical trials. 19 of the 20 ligands show an affinity below 100 nM at the human
      adenosine A1 receptor (hA1AR) and display a wide range of residence times at this
      target (from approx. 5 min (compound 10) up to 132 min (compound 5)). Structure
      affinity and structure-kinetics relationships were established, and computational
      studies of a homology model of the hA1AR revealed crucial interactions for both
      the affinity and dissociation kinetics of this family of ligands. These results
      were also combined with global metrics (Ligand Efficiency, cLogP), showing the
      importance of binding kinetics as an additional way to better select a drug
      candidate amongst seemingly similar leads. 

PMID- 26210505
TI  - Melanoma-targeted delivery system (part 1): design, synthesis and evaluation of
      releasable disulfide drug by glutathione.
AB  - Here we describe the design and synthesis of a prodrug developed for pigmented
      melanoma therapy, consisting of a Melanin-Targeting Probe (MTP) conjugated to 5
      iodo-2'-deoxyuridine (IUdR) with a reduction-sensitive pre-determined breaking
      point. Compared with the non-cleavable conjugate (17b), prodrug (17a) bearing a
      self-immolative disulfide linker achieved complete release of IUdR within 20 min
      in the presence of reducing agents such as DTT or glutathione. Analytical results
      also showed that prodrug (17a) was more sensitive than parent non-cleavable
      conjugate (17b) for a concentration range of glutathione similar to that found in
      the intracellular compartment of tumours. 

PMID- 26210507
TI  - Combating highly resistant emerging pathogen Mycobacterium abscessus and
      Mycobacterium tuberculosis with novel salicylanilide esters and carbamates.
AB  - In the Mycobacterium genus over one hundred species are already described and new
      ones are periodically reported. Species that form colonies in a week are
      classified as rapid growers, those requiring longer periods (up to three months)
      are the mostly pathogenic slow growers. More recently, new emerging species have
      been identified to lengthen the list, all rapid growers. Of these, Mycobacterium
      abscessus is also an intracellular pathogen and it is the most chemotherapy
      resistant rapid-growing mycobacterium. In addition, the cases of multidrug
      resistant Mycobacterium tuberculosis infection are also increasing. Therefore
      there is an urgent need to find new active molecules against these threatening
      strains. Based on previous results, a series of salicylanilides, salicylanilide 5
      chloropyrazinoates and carbamates was designed, synthesized and characterised.
      The compounds were evaluated for their in vitro activity on M. abscessus,
      susceptible M. tuberculosis H37Rv, multidrug-resistant (MDR) M. tuberculosis MDR
      A8, M. tuberculosis MDR 9449/2006 and on the extremely-resistant Praha 131 (XDR)
      strains. All derivatives exhibited a significant activity with minimum inhibitory
      concentrations (MICs) in the low micromolar range. Eight salicylanilide
      carbamates and two salicylanilide esters exhibited an excellent in vitro activity
      on M. abscessus with MICs from 0.2 to 2.1 MUM, thus being more effective than
      ciprofloxacin and gentamicin. This finding is potentially promising,
      particularly, as M. abscessus is a threateningly chemotherapy-resistant species.
      M. tuberculosis H37Rv was inhibited with MICs from 0.2 MUM, and eleven compounds
      have lower MICs than isoniazid. Salicylanilide esters and carbamates were found
      that they were effective also on MDR and XDR M. tuberculosis strains with MICs
      >=1.0 MUM. The in vitro cytotoxicity (IC50) was also determined on human MonoMac
      6 cells, and selectivity index (SI) of the compounds was established. In general,
      salicylanilide derivatives substituted by halogens on both salicyl and aniline
      rings showed better activity, than 4-benzoylaniline derivatives. The ester or
      carbamate bond formation of parent salicylanilides mostly retained or improved
      antimycobacterial potency with moderate selectivity. 

PMID- 26210508
TI  - Design, synthesis of benzocoumarin-pyrimidine hybrids as novel class of
      antitubercular agents, their DNA cleavage and X-ray studies.
AB  - A series of 2-(2-(4-fluorobenzyl)-6-(substituted phenyl) pyrimidin-4-yl)-3H
      benzo[f]chromen-3-one derivatives (1a-1o) were selectively prepared in high
      yields under microwave irradiation. The synthesized compounds were characterized
      by elemental and spectroscopic analysis; in addition the structures of compound
      (1a), (1b) and (1j) were elucidated by the X-ray diffraction technique. Compounds
      (1a-1o) were evaluated for their in-vitro antitubercular activity while the most
      active compounds were further subjected for their cytotoxicity and DNA cleavage
      study. Results revealed that most of the tested compounds displayed potent
      antitubercular activity with MIC in the range 0.05-2.81 MUg/mL. Among them,
      compound (1b) possessed excellent activity (MIC 0.05 MUg/mL) against M.tb H37Rv
      strain and exhibited low level of cytotoxicity against Vero cells, which
      suggested compound (1b) is a promising lead for subsequent investigation in
      search of new antitubercular agents. DNA cleavage by gel electrophoresis method
      revealed that compounds (1b, 1g, 1k and 1n) were found to cleave the DNA
      completely. 

PMID- 26210509
TI  - Role of Jo-1 in the Immunopathogenesis of the Anti-synthetase Syndrome.
AB  - Histidyl-tRNA synthetase (HRS = Jo-1) represents a key autoantibody target in the
      anti-synthetase syndrome that is marked by myositis as well as extra-muscular
      organ complications including interstitial lung disease (ILD). Over the last 25
      years, a wealth of clinical, epidemiological, genetic, and experimental data have
      collectively supported a role for Jo-1 in mediating deleterious cell-mediated,
      adaptive immune responses contributing to the disease phenotype of the anti
      synthetase syndrome. Complementing these studies, more recent work suggests that
      unique, non-enzymatic functional properties of Jo-1 also endow this antigen with
      the capacity to activate components of the innate immune system, particularly
      cell surface as well as endosomal Toll-like receptors and their downstream
      signaling pathways. Combining these facets of Jo-1-mediated immunity now supports
      a more integrated model of disease pathogenesis that should lead to improved
      therapeutic targeting in the anti-synthetase syndrome and related subsets of
      idiopathic inflammatory myopathy.

PMID- 26210511
TI  - Overview of multiple testing methodology and recent development in clinical
      trials.
AB  - Multiplicity control is an important statistical issue in clinical trials where
      strong control of the type I error rate is required. Many multiple testing
      methods have been proposed and applied to address multiplicity issues in clinical
      trials. This paper provides an application oriented and comprehensive overview of
      commonly used multiple testing procedures and recent developments in statistical
      methodology in multiple testing in clinical trials. Commonly used multiple
      testing procedures are applied to test non-hierarchical hypotheses and
      gatekeeping procedures can be used to test hierarchically ordered hypotheses
      while controlling the overall type I error rate. The recently developed graphical
      approach has the flexibility to integrate hierarchical and non-hierarchical
      procedures into one framework. A graphical multiple testing procedure with "no
      dead-end" provides an opportunity to fully recycle alpha across hypothesis
      families. Two hypothetical clinical trial examples are used to illustrate
      applications of these procedures. The advantages and disadvantages of the
      different procedures are briefly discussed.

PMID- 26210510
TI  - Lipid and Metabolic Changes in Rheumatoid Arthritis.
AB  - While the most obvious manifestations of rheumatoid arthritis (RA) involve
      inflammation and damage in the synovial joints, the systemic effects of the
      condition are widespread and life-threatening. Of particular interest is the
      'lipid paradox' of RA, where patients with a numerically equivocal starting lipid
      profile have a significantly raised risk of cardiovascular (CV) events and
      response to therapy results in a 'normalization' of lipid levels and reduction in
      events. Changes in lipids can be seen before overt disease manifestations which
      suggest that they are closely linked to the more widespread inflammation-driven
      metabolic changes associated with tumour necrosis factor (TNF). Cachexia involves
      a shift in body mass from muscle to fat, which may or may not directly increase
      the cardiovascular risk. However, since TNF inhibition is associated with
      reduction in cardiovascular events, it does suggest that these widespread
      metabolic changes involving lipids are of importance. Analysis of single lipids
      or metabolites have been used to identify some of the key changes, but more
      recently, metabolomic and lipidomic approaches have been applied to identify a
      broad spectrum of small molecule changes and identify potentially altered
      metabolic pathways. Further work is needed to understand fully the metabolic
      changes in lipid profiles and identify novel ways of targeting desired profile
      changes, but work so far does suggest that a better understanding may allow
      management of patients to downregulate the systemic effects of their disease that
      puts them at risk of cardiovascular complications. 

PMID- 26210512
TI  - Probiotics for Clostridium difficile infection in adults (PICO): Study protocol
      for a double-blind, randomized controlled trial.
AB  - BACKGROUND: Clostridium difficile is a pathogen of rapidly increasing public
      health importance. An estimated quarter of a million Clostridium difficile
      infections (CDI) occur in the United States annually, at a resultant cost of
      14,000 deaths and 1 billion dollars. Clostridium difficile related deaths have
      risen 400% over the last decade, and current standard antibiotic treatments are
      only 75 to 85% successful. Besides increasing the risk of antibiotic resistance
      and side effects, these treatments are very expensive. The most vulnerable
      population for Clostridium difficile is older adults, who make up approximately
      half of the cases, but account for 90% of the related deaths. Probiotics may have
      potential as adjunctive therapeutic agents for CDIs, however, current data is
      limited. METHODS: This pilot study is a single-site, randomized, placebo
      controlled, double-blind, phase two clinical trial. The trial primarily evaluates
      the effect of four weeks of probiotic therapy in addition to standard of care on
      Clostridium difficile diarrhea duration and recurrence. Secondary outcomes
      include effect on fecal cytokines, fecal lactoferrin, and Clostridium difficile
      toxin density in stool, as well as patient functional status. DISCUSSION: This
      pilot study will determine the feasibility and effect size to conduct larger
      randomized controlled trials of probiotic interventions in patients with CDI, to
      determine the impact of probiotics on the symptoms of CDI. ClinicalTrials.gov
      Identifier: NCT01680874.

PMID- 26210513
TI  - An Effective Neurofeedback Intervention to Improve Social Interactions in
      Children with Autism Spectrum Disorder.
AB  - Neurofeedback training (NFT) approaches were investigated to improve behavior,
      cognition and emotion regulation in children with autism spectrum disorder (ASD).
      Thirteen children with ASD completed pre-/post-assessments and 16 NFT-sessions.
      The NFT was based on a game that encouraged social interactions and provided
      feedback based on imitation and emotional responsiveness. Bidirectional training
      of EEG mu suppression and enhancement (8-12 Hz over somatosensory cortex) was
      compared to the standard method of enhancing mu. Children learned to control mu
      rhythm with both methods and showed improvements in (1) electrophysiology:
      increased mu suppression, (2) emotional responsiveness: improved emotion
      recognition and spontaneous imitation, and (3) behavior: significantly better
      behavior in every-day life. Thus, these NFT paradigms improve aspects of behavior
      necessary for successful social interactions. 

PMID- 26210514
TI  - Leisure Activity Enjoyment of Children with Autism Spectrum Disorders.
AB  - Enjoyment is a fundamental component of activity participation. This study
      compared leisure activity enjoyment experienced by typically developing children
      (TD; n = 64) and those with autism spectrum disorders (ASD; n = 67) from age 6 to
      13. The TD children enjoyed formal and physical activities significantly more
      than the children with ASD. Symptom severity was negatively related to enjoyment
      of overall, formal, physical and social activities. Older children with ASD
      enjoyed overall, informal, recreational, and self-improvement activities
      significantly less than younger children, but no differences were seen across TD
      age groups. Children with ASD enjoyed swimming significantly more than TD
      children. Understanding patterns of activity enjoyment is useful for being better
      able to address a child's motivation to participate in various life activities.

PMID- 26210515
TI  - Effectiveness of a Standardized Equine-Assisted Therapy Program for Children with
      Autism Spectrum Disorder.
AB  - In this study the effectiveness of an equine-assisted therapy (EAT) in improving
      adaptive and executive functioning in children with autism spectrum disorder
      (ASD) was examined (children attending EAT, n = 15, control group n = 13;
      inclusion criteria: IQ > 70). Therapeutic sessions consisted in structured
      activities involving horses and included both work on the ground and riding.
      Results indicate an improvement in social functioning in the group attending EAT
      (compared to the control group) and a milder effect on motor abilities. Improved
      executive functioning was also observed (i.e. reduced planning time in a problem
      solving task) at the end of the EAT program. Our findings provide further support
      for the use of animal-assisted intervention programs as complementary
      intervention strategies for children with ASD.

PMID- 26210516
TI  - The Vineland-II in Preschool Children with Autism Spectrum Disorders: An Item
      Content Category Analysis.
AB  - We investigated which item subsets of the Vineland-II can discriminate low
      functioning preschoolers with ASD from matched peers with other
      neurodevelopmental disorders, using a regression analysis derived from a
      normative sample to account for cognitive and linguistic competencies. At
      variance with the typical profile, a pattern with Communication more impaired
      than Socialization was observed. The source of the frequently reported
      Socialization delay in ASD appears to be in Playing and Imitating skills only,
      not in other social adaptive behavior skills. The combination of item subsets
      Playing, Following instructions, Beginning to talk, and Speech skills provided
      the best discrimination between the two clinical groups. Evaluation of the
      Vineland-II score on item content categories is a useful procedure for a more
      efficient clinical description. 

PMID- 26210518
TI  - Preserved Proactive Interference in Autism Spectrum Disorder.
AB  - In this study, we aimed to evaluate further the functioning and structuring of
      the semantic system in autism spectrum disorders (ASD). We analyzed the
      performance of 19 high-functioning young adults with ASD and a group of 20 age-,
      verbal IQ- and education-matched individuals with the Proactive Interference (PI)
      Paradigm to evaluate semantic functioning in ASD (Experiment 1). In Experiment 2,
      we analyzed the performances of both groups in a PI paradigm with manipulation of
      the level of typicality. In both experiments, we observed significant effects of
      trial and group but no trial by group interactions, which we interpreted as
      robust evidence of preserved PI (build up effect) that indicated the preservation
      of semantic mechanisms of encoding and retrieval. 

PMID- 26210517
TI  - Lexical Processing in School-Age Children with Autism Spectrum Disorder and
      Children with Specific Language Impairment: The Role of Semantics.
AB  - Children with autism spectrum disorder (ASD) and specific language impairment
      (SLI) often have immature lexical-semantic knowledge; however, the organization
      of lexical-semantic knowledge is poorly understood. This study examined lexical
      processing in school-age children with ASD, SLI, and typical development, who
      were matched on receptive vocabulary. Children completed a lexical decision task,
      involving words with high and low semantic network sizes and nonwords. Children
      also completed nonverbal updating and shifting tasks. Children responded more
      accurately to words from high than from low semantic networks; however, follow-up
      analyses identified weaker semantic network effects in the SLI group.
      Additionally, updating and shifting abilities predicted lexical processing,
      demonstrating similarity in the mechanisms which underlie semantic processing in
      children with ASD, SLI, and typical development. 

PMID- 26210519
TI  - Boys with Asperger Syndrome Grow Up: Psychiatric and Neurodevelopmental Disorders
      20 Years After Initial Diagnosis.
AB  - We examined comorbid psychiatric and neurodevelopmental disorders in fifty adult
      males (mean age 30 years) with Asperger syndrome (AS) diagnosed in childhood and
      followed up prospectively for almost two decades (13-26 years). Only three of the
      50 men had never met criteria for an additional psychiatric/neurodevelopmental
      diagnosis and more than half had ongoing comorbidity (most commonly either ADHD
      or depression or both). Any psychiatric comorbidity increased the risk of poorer
      outcome. The minority of the AS group who no longer met criteria for a full
      diagnosis of an autism spectrum disorder were usually free of current psychiatric
      comorbidity. The high rate of psychiatric/neurodevelopmental comorbidities
      underscores the need for a full psychiatric/neurodevelopmental assessment at
      follow-up of males with AS.

PMID- 26210520
TI  - The prognostic value of the neoadjuvant response index in triple-negative breast
      cancer: validation and comparison with pathological complete response as outcome
      measure.
AB  - The Neoadjuvant response index (NRI) has been proposed as a simple measure of
      downstaging by neoadjuvant treatment in breast cancer. It was previously found to
      predict recurrence-free survival (RFS) in triple-negative (TN) breast cancer. It
      was at least as accurate as the standard binary system, the absence or presence
      of a pathological complete remission (pCR), which is the commonly employed
      outcome measure. The NRI was evaluated in an independent consecutive series of
      patients to validate the previous findings. Univariable and multivariable
      analyses were done to assess the predictive value of clinical parameters and of
      the NRI for RFS. We combined the original and validation series of patients to
      build a multivariable predictive model for RFS after neoadjuvant chemotherapy in
      TN breast cancer. The validation set (N = 108) confirmed that patients with a
      higher-than-median NRI (>0.7) had excellent RFS (P = 0.002), similar to that of
      patients who had achieved a pCR. Multivariable analysis in 191 patients showed
      that the NRI was a strong independent predictor of RFS (P = 0.0002), with N-stage
      (P = 0.001) and T-stage (P = 0.014) ranking second and third, respectively.
      Importantly, among patients who did not achieve a pCR (NRI values below 1),
      higher NRI values were still associated with better RFS. The NRI is a simple
      method and a practical tool to predict RFS in TN breast cancer patients treated
      with neoadjuvant chemotherapy. It adds prognostic information to the presence or
      absence of pCR and could be useful to compare the efficacies of different
      chemotherapy regimens.

PMID- 26210521
TI  - Breast cancer after prophylactic mastectomy (bilateral or contralateral
      prophylactic mastectomy), a clinical entity: presentation, management, and
      outcomes.
AB  - Contralateral prophylactic mastectomy (CPM) and bilateral prophylactic mastectomy
      (BPM) markedly decrease the possibility of new breast cancer (BC) ipsilateral to
      the prophylactic mastectomy (PM). Given its relative infrequency, little is known
      about the clinical characteristics, presentation, and management of BC after PM.
      Between 1960 and 1993, 1065 women underwent BPM and 1643 women with unilateral BC
      treated with therapeutic mastectomy underwent CPM at our institution. Medical
      records were reviewed, and study-specific questionnaires were sent to all women.
      BC after PM included locoregional invasive BC or ductal carcinoma in situ
      ipsilateral to the PM. BC developed ipsilateral to the PM in 25 patients (13
      after BPM; 12 after therapeutic mastectomy and CPM). Median follow-up after PM
      was 22 years (range 3-34 years). Presentations included clinically isolated local
      disease in 17 patients (68%); disease limited to the axilla without evidence of
      local primary disease in 4 (16%); synchronous local and axillary disease in 1
      (4%); and synchronous local disease and distant metastases in 3 (12%). The 17
      patients presenting with isolated local disease were most commonly managed with
      completion or redo mastectomy (65%) or local excision (29 %), followed by
      consideration of adjuvant therapy. The 5-year disease-free survival estimate was
      69% (95% CI 52-94%) for the 22 patients who had isolated locoregional BC after PM
      and were treated with curative intent. Although rare, BC after PM can occur. The
      most common presentation, disease localized to the mastectomy site, can be
      managed with resection and consideration of adjuvant therapy.

PMID- 26210522
TI  - Epidemiology of new-onset paroxysmal atrial fibrillation in the General Intensive
      Care Unit population and after discharge from ICU. A retrospective
      epidemiological study.
AB  - BACKGROUND: Evidence of various cardiac arrhythmias in septic patients has been
      demonstrated by multiple clinical reports and observations. Most cardiac
      arrhythmias in sepsis are new-onset and may be related to sepsis-induced
      myocardial dysfunction. We propose to investigate and analyze data of new-onset
      paroxysmal atrial fibrillation (AF) in a critically ill septic population.
      METHODS: This is a retrospective epidemiologic study. We collected clinical data
      from two hundred septic patients who developed a new episode of atrial
      fibrillation during their hospitalization in General Intensive Care Unit (GICU)
      between January 2007 and June 2013. RESULTS: Of these 200 septic patients, 81
      septic patients developed a new episode of AF and included in the present study.
      Thirty-seven patients had no past medical history of atrial fibrillation (AF) or
      antiarrhythmic therapy (new episode of atrial fibrillation, Group 1) and 44 had
      previously known episodes of atrial fibrillation and were prescribed
      antiarrhythmic therapy at home (Group 2). Group 2 patients had longer duration of
      recurrent episodes of atrial fibrillation compared to patients in Group 1 (11.07
      +/- 8.7 vs. 7.4 +/- 6.1 days; P = 0.013). The overall ICU and in-hospital
      mortality rate was similar in both study groups. There was no significant
      difference in new stroke and pulmonary embolism (PE) between both study groups (P
      > 0.05). CONCLUSION: In the present study we demonstrated no difference in
      morbidity and mortality rate in-ICU and after discharge between septic patients
      who had previous AF episodes and patients who had no previous past medical
      history of any cardiac arrhythmias.

PMID- 26210523
TI  - Assessment of posterior accessory great saphenous vein of the leg using
      ultrasonography: a preliminary study.
AB  - PURPOSE: To assess the frequency and anatomic distributions of the posterior
      accessory great saphenous vein of the leg (PAGSVL) and its insufficiency rate
      using ultrasonography (US) in patients who presented with clinical, etiologic,
      anatomic, and pathophysiologic (CEAP) scores of 1 and above. METHODS: A
      prospective US study on 200 limbs of 100 consecutive patients with CEAP scores of
      1 and above. RESULTS: Right PAGSVL was seen in 45 % (45 cases), whereas left
      PAGSVL was seen in 54 % (54 cases) of the patients [49.5 % (99 limbs) in total]
      (p < 0.05). PAGSVL insufficiency was present in 6 % (6 cases) of the patients [6
      limbs in total (6.06 %)]. The type of PAGSVL joining to the great saphenous vein
      (GSV) was above the knee level in 4 % (4 limbs), at the knee level in 14 % (14
      limbs), and below the knee level in 74 % of patients (74 limbs). The relationship
      between posterior tibial perforators and PAGSVL was seen in 3.03 % of cases (3
      limbs). There was no statistically significant relationship between PAGSVL
      insufficiency and the presence of posterior tibial perforators (p = 0.55) or
      between the presence of PAGSVL and the GSV insufficiency. CONCLUSION: PAGSVL was
      seen in half of the limbs with CEAP scores of 1 and above. The frequency of
      PAGSVL was more common in the left limbs than the right limbs. There was no
      statistically significant relationship between the presence of PAGSVL, GSV
      insufficiency, and different CEAP scores. The PAGSVL often joined to the GVS
      below the knee, but could also join above the knee.

PMID- 26210524
TI  - Pattern, variability, and hemispheric differences of the subparietal sulcus on
      multiplanar reconstructed MR images.
AB  - PURPOSE: The aim of this study was to analyze variations in the morphological
      features of the subparietal sulcus (SPS) and to investigate interhemispheric and
      gender differences in these variations using multiplanar reconstructed (MPR)
      magnetic resonance (MR) images. METHODS: Two hundred subjects with normal cranial
      MR imaging, including high-resolution T1-weighted volumetric data, were enrolled
      in the study. The sagittal or oblique sagittal MPR images created from high
      resolution T1-weighted data were analyzed for the following morphological
      features: the SPS patterns, the continuity of the SPS with the cingulate sulcus
      and parieto-occipital sulcus (POS), and the presence of upwardly directed SPS
      branches reaching to the hemispheric surface. Interindividual variability of the
      morphologic features, hemispheric asymmetry, and gender differences were
      investigated. RESULTS: Considerable variations were found in the morphological
      features of the SPS. The H-pattern, no connection with the cingulate sulcus or
      the POS, and one upwardly directed branch reaching the hemispheric surface were
      most commonly observed morphologic features of the SPS in 45.2, 41.8, and 48 % of
      the all hemispheres, respectively. Furthermore, the connection of the SPS only
      with the cingulate sulcus and the presence of two upwardly directed branches
      reaching the hemispheric surface showed the significant leftward asymmetry (P <
      0.05). CONCLUSIONS: Our study demonstrated the extensive morphological
      variability of the SPS and the hemispheric asymmetry for some morphological
      features. Knowledge of these variations and their hemispheric asymmetry may be
      helpful for surgical approaches in neurosurgery and structure-function
      correlations in functional neuroimaging studies involving the posteromedial
      hemisphere.

PMID- 26210525
TI  - The effects of changes in utilization and technological advancements of cross
      sectional imaging on radiologist workload.
AB  - RATIONALE AND OBJECTIVES: To examine the effect of changes in utilization and
      advances in cross-sectional imaging on radiologists' workload. MATERIALS AND
      METHODS: All computed tomography (CT) and magnetic resonance imaging (MRI)
      examinations performed at a single institution between 1999 and 2010 were
      identified and associated with the total number of images for each examination.
      Annual trends in institutional numbers of interpreted examinations and images
      were translated to changes in daily workload for the individual radiologist by
      normalizing to the number of dedicated daily CT and MRI work assignments,
      assuming a 255-day/8-hour work day schedule. Temporal changes in institutional
      and individual workload were assessed by Sen's slope analysis (Q = median slope)
      and Mann-Kendall test (Z = Z statistic). RESULTS: From 1999 to 2010, a total of
      1,517,149 cross-sectional imaging studies (CT = 994,471; MRI = 522,678)
      comprising 539,210,581 images (CT = 339,830,947; MRI = 199,379,634) were
      evaluated at our institution. Total annual cross-sectional studies steadily
      increased from 84,409 in 1999 to 147,336 in 2010, representing a twofold increase
      in workload (Q = 6465/year, Z = 4.2, P < .0001). Concomitantly, the number of
      annual departmental cross-sectional images interpreted increased from 9,294,140
      in 1990 to 94,271,551 in 2010, representing a 10-fold increase (Q = 8707876/year,
      Z = 4.5, P < .0001). Adjusting for staffing changes, the number of images
      requiring interpretation per minute of every workday per staff radiologist
      increased from 2.9 in 1999 to 16.1 in 2010 (Q = 1.7/year, Z = 4.3, P < .0001).
      CONCLUSIONS: Imaging volumes have grown at a disproportionate rate to imaging
      utilization increases at our institution. The average radiologist interpreting CT
      or MRI examinations must now interpret one image every 3-4 seconds in an 8-hour
      workday to meet workload demands.

PMID- 26210526
TI  - Changes to Radiology: Simpler is Better.

PMID- 26210527
TI  - Characteristics and kinetic studies of Hydrilla verticillata pyrolysis via
      thermogravimetric analysis.
AB  - The pyrolysis characteristics and kinetic of Hydrilla verticillata (HV) have been
      investigated using non-isothermal thermogravimetric analysis. The results showed
      that the pyrolysis behavior of HV can be divided into two independent stages. The
      kinetics of Stage I was investigated using a distributed activation energy model
      (DAEM) with discrete 99 first-order reactions. Stage II was an independent stage
      which corresponds to the decomposition of calcium oxalate, whose kinetics was
      studied using iso-conversional method together with compensation effect and
      master-plots method. The activation energies ranged from 92.39 to 506.17 and
      190.42 to 222.48 kJ/mol for the first and second stages respectively. Calculated
      data gave very good fit to the experimental data.

PMID- 26210528
TI  - Nitrogen recovery from pig slurry in a two-chambered bioelectrochemical system.
AB  - Abiotic batch experiments showed that ammonia migration from anode to cathode was
      favored by an increase in voltage, from 39.9% to 44.6%, using synthetic media. A
      slight increase in ammonia migration was observed when using pig slurry, reaching
      a maximum of 49.9%. In a continuously MFC fed with pig slurry with a
      stripping/absorption unit coupled to the cathode chamber, the highest nitrogen
      flux (7.2 g N d(-1) m(-2)) was achieved using buffer as catholyte. Nitrogen flux
      increased to 10.3 g N d(-1) m(-2) when shifting to MEC mode. A clear improvement
      in nitrogen flux (25.5 g N d(-1) m(-2)) was observed when using NaCl as
      catholyte. Besides, ammonia stripping was favored, reaching a nitrogen recovery
      of 94.3% in the absorption column, due to the high pH reached in the cathode. The
      microbial community analysis revealed an enrichment of certain taxonomic
      Eubacterial and Archaeal groups when the system shifted from MFC to MEC mode.

PMID- 26210529
TI  - Component analysis and heavy metal adsorption ability of extracellular polymeric
      substances (EPS) from sulfate reducing bacteria.
AB  - Extracellular polymeric substances (EPS) play an important role in the treatment
      of acid mine drainage (AMD) by sulfate-reducing bacteria (SRB). In this paper,
      Desulfovibrio desulfuricans was used as the test strain to explore the effect of
      heavy metals on the components and adsorption ability of EPS. Fourier-transform
      infrared (FTIR) spectroscopy analysis results showed that heavy metals did not
      influence the type of functional groups of EPS. Potentiometric titration results
      indicated that the acidic constants (pKa) of the EPS fell into three ranges of
      3.5-4.0, 5.9-6.7, and 8.9-9.8. The adsorption site concentrations of the surface
      functional groups also increased. Adsorption results suggested that EPS had a
      specific binding affinity for the dosed heavy metal, and that EPS extracted from
      the Zn(2+)-dosed system had a higher binding affinity for all heavy metals.
      Additionally, Zn(2+) decreased the inhibitory effects of Cd(2+) and Cu(2+) on the
      SRB. 

PMID- 26210530
TI  - Hydrogen production from switchgrass via an integrated pyrolysis-microbial
      electrolysis process.
AB  - A new approach to hydrogen production using an integrated pyrolysis-microbial
      electrolysis process is described. The aqueous stream generated during pyrolysis
      of switchgrass was used as a substrate for hydrogen production in a microbial
      electrolysis cell, achieving a maximum hydrogen production rate of 4.3 L H2/L
      anode-day at a loading of 10 g COD/L-anode-day. Hydrogen yields ranged from 50+/
      3.2% to 76+/-0.5% while anode Coulombic efficiency ranged from 54+/-6.5% to 96+/
      0.21%, respectively. Significant conversion of furfural, organic acids and
      phenolic molecules was observed under both batch and continuous conditions. The
      electrical and overall energy efficiency ranged from 149-175% and 48-63%,
      respectively. The results demonstrate the potential of the pyrolysis-microbial
      electrolysis process as a sustainable and efficient route for production of
      renewable hydrogen with significant implications for hydrocarbon production from
      biomass.

PMID- 26210531
TI  - Biopreservative methods to control the growth of foodborne pathogens on fresh-cut
      lettuce.
AB  - Fruits and vegetables can become contaminated by foodborne pathogens such as
      Escherichia coli O157:H7, Salmonella and Listeria monocytogenes, and it has been
      demonstrated that current industrial sanitizing treatments do not eliminate the
      pathogens when present. Chemical control is widely used, but biological control
      appears to be a better solution, mainly using the native microbiota present on
      fresh produce. The first objective of this study was to isolate native microbiota
      from whole and fresh-cut produce and to determine whether these bacteria were
      antagonistic toward foodborne pathogens. A total of 112 putative antagonist
      isolates were screened for their ability to inhibit the growth of Salmonella
      enterica on lettuce disks. Five different genera reduced S. enterica growth more
      than 1-log unit at 20 degrees C at the end of 3 days. When tested against L.
      monocytogenes 230/3, only Pseudomonas sp. strain M309 (M309) was able to reduce
      pathogen counts by more than 1-log unit. Therefore, M309 strain was selected to
      be tested on lettuce disks at 10 degrees C against S. enterica, E. coli O157:H7
      and L. monocytogenes. M309 strain was only able to reduce S. enterica and E. coli
      O157:H7 populations. The second objective was to test different biopreservative
      methods including M309 strain, Pseudomonas graminis CPA-7 (CPA-7), bacteriophages
      (Listex P100 and Salmonelex) and nisin at conditions simulating commercial
      applications against Salmonella and L. monocytogenes on fresh-cut lettuce. The
      addition of the biopreservative agents did not result in a significant reduction
      of Salmonella population. However, CPA-7 strain together with nisin reduced L.
      monocytogenes numbers after 6 days of storage at 10 degrees C. The cocktail of
      Salmonella and L. monocytogenes was not markedly inactivated by their respective
      bacteriophage solutions. This study highlighted the potential of biocontrol, but
      the combination with other technologies may be required to improve their
      application on fresh-cut lettuce.

PMID- 26210532
TI  - Characterization of extended-spectrum beta-lactamase (ESBL) producing non
      typhoidal Salmonella (NTS) from imported food products.
AB  - Food contaminated with extended-spectrum beta-lactamase (ESBL)-producing
      Salmonella enterica has emerged as an important global issue due to the
      international food-product trade. Therefore, the purpose of this study was to
      investigate whether imported food products can serve as a reservoir for non
      typhoidal Salmonella (NTS) that can transmit beta-lactam-resistance to humans
      through ingestion of the contaminated food. NTS isolates (n=110) were collected
      from various imported food products (n=3480) from 2011 to 2013. The NTS isolates
      were analyzed by serotyping, antimicrobial susceptibility tests, and plasmid
      profiling. Salmonella ser. Weltevreden, Salmonella ser. Newport, Salmonella ser.
      Senftenberg, Salmonella ser. Virchow, Salmonella ser. Enteritidis, Salmonella
      ser. Typhimurium, and Salmonella ser. Bareilly were the most prevalent serovars.
      Nine NTS strains were resistant to ampicillin and/or one or more cephalosporins
      (MIC>32 MUg/mL). Polymerase chain reaction (PCR) detection revealed that all nine
      isolates carried the bla(TEM-1) beta-lactamase gene, with or without the bla(CTX
      M-9) or bla(OXA-1) genes. Two isolates, PSS_913 and PSS_988, exhibited decreased
      susceptibility to extended-spectrum cephalosporins and ampicillin. Plasmids
      ranging in size from less than 8 to over 165 kbp, from all of the 9 resistant
      isolates, belonged to the IncHI1, IncI1, IncN, or IncX groups. Conjugation
      experiments and Southern hybridization, using bla(TEM-1), confirmed the plasmid
      mediated transfer of ESBL genes, which resulted in increased MICs of beta-lactams
      for Escherichia coli transconjugants. The contamination of imported food products
      by NTS with conjugative plasmid-borne ESBL genes may contribute to the spread of
      ESBL-producing NTS and compromise the therapeutic activity of extended-spectrum
      beta-lactam antibiotics.

PMID- 26210533
TI  - Application of water-assisted ultraviolet light processing on the inactivation of
      murine norovirus on blueberries.
AB  - In this study, a novel set-up using water-assisted UV processing was developed
      and evaluated for its decontamination efficacy against murine norovirus (MNV-1)
      inoculated on fresh blueberries for both small and large-scale experimental
      setups. Blueberries were skin-inoculated with MNV-1 and treated for 1-5 min with
      UV directly (dry UV) or immersed in agitated water during UV treatment (water
      assisted UV). The effect of the presence of 2% (v/v) blueberry juice or 5%
      crushed blueberries (w/w) in wash water was also evaluated. Results showed that
      water-assisted UV treatment generally showed higher efficacies than dry UV
      treatment. With 12,000 J/m(2) UV treatment in small-scale setup, MNV reductions
      of >4.32- and 2.48-log were achieved by water-assisted UV and dry UV treatments,
      respectively. Water-assisted UV showed similar inactivating efficacy as 10-ppm
      chlorine wash. No virus was detected in wash water after UV treatment or chlorine
      wash. MNV-1 was more easily killed on skin-inoculated blueberries compared with
      calyx-inoculated berries. When clear water was used as wash water in the large
      scale setup, water-assisted UV treatment (UV dose of 12,000 J/m(2)) resulted in
      >3.20 log and 1.81 log MNV-1 reductions for skin- and calyx-inoculated berries,
      respectively. The presence of 2% blueberry juice in wash water decreased the
      decontamination efficacy of water-assisted UV and chlorine washing treatments. To
      improve the inactivation efficacy, the effect of combining water-assisted UV
      treatment with chlorine washing was also evaluated. The combined treatment had
      better or similar inactivation efficacy compared to water-assisted UV treatment
      and chlorine washing alone. Findings of this study suggest that water-assisted UV
      treatment could be used as an alternative to chlorine washing for blueberries and
      potentially for other fresh produce.

PMID- 26210534
TI  - Use of phytic acid and hyper-salting to eliminate Escherichia coli O157:H7 from
      napa cabbage for kimchi production in a commercial plant.
AB  - The aim of this study was to develop a new salting method using natural phytic
      acid (PA) to ensure the microbiological safety and quality of salted napa cabbage
      used for kimchi production. The production of salted napa cabbage involves
      several stages: trimming, hyper-salting (20% NaCl) for up to 1h, salting (10%
      NaCl for 10-18 h), three sequential washes in water (30s for each), and draining
      (2 h). Two separate experiments were performed: one to determine the appropriate
      treatment conditions and a second to validate applicability under commercial
      conditions. In Experiment I, the effects of hyper-salting with PA on Escherichia
      coli O157:H7 numbers were tested in the laboratory. The following variables were
      monitored: 1) PA concentration (1, 2, 3%, w/w); 2) the ratio of the sample weight
      to the total volume of the solution (1:1.5, 1:3, or 1:6); 3) the hyper-salting
      time (30 or 60 min); and 4) the salting time (2, 5, or 8 h). A procedure that
      achieved a >5-log reduction in the E. coli O157:H7 population was then tested in
      an actual kimchi processing plant (Experiment II). The results from Experiment I
      showed that bactericidal efficacy increased as all the measured variables
      increased (p<0.05). Hyper-salting with 2% PA at a sample-to-water ratio (w/v) of
      1:3 and 1:6 for 60 min resulted in a >5-log CFU/g reduction in the E. coli
      O157:H7 population. Further salting for 5h completely eliminated (<1-log CFU/g)
      all bacteria. Thus, hyper-salting with PA 2% at a sample-to-water ratio of 1:3
      for 60 min, followed by salting for 5h, was tested under large-scale production
      conditions. The results revealed that the initial aerobic plate counts (APC),
      total coliform counts (TC), and fecal coliform counts (FC) were 6.6, 3.4, and 2.8
      log CFU/g, respectively. The selected protocol reduced these values by 3.7-, >2.4
      , and >1.8-log CFU/g, respectively. The 5h salting step maintained the TC and FC
      at <1-log CFU/g; however, the APC recovered somewhat. The pH and salinity of the
      treated salted napa cabbages were within the ranges required for kimchi
      production (pH 5.1-5.3 and 1.5-2.0%, respectively). These results suggest that
      this novel method of salting food ensures microbiological safety and reduces the
      production time.

PMID- 26210535
TI  - A selective review of prenatal exercise guidelines since the 1950s until present:
      Written for women, health care professionals, and female athletes.
AB  - BACKGROUND: Traditional society values have long-held the notion that the
      pregnant woman is construed as a risk to her growing fetus and is solely
      responsible for controlling this risk to ensure a healthy pregnancy. It is hard
      to ignore the participation of pregnant women in sport and exercise today,
      especially in high-level sports and popular fitness programs such as CrossFitTM.
      This challenges both traditional and modern prenatal exercise guidelines from
      health care professionals and governing health agencies. The guidelines and
      perceived limitations of prenatal exercise have drastically evolved since the
      1950s. AIM: The goal of this paper is to bring awareness to the idea that much of
      the information regarding exercise safety during pregnancy is hypersensitive and
      dated, and the earlier guidelines had no scientific rigor. Research is needed on
      the upper limits of exercise intensity and exercise frequency, as well as their
      potential risks (if any) on the woman or fetus. DISCUSSION: Pregnant women are
      physically capable of much more than what was once thought. There is still
      disagreement about the types of exercise deemed appropriate, the stage at which
      exercise should begin and cease, the frequency of exercise sessions, as well as
      the optimal level of intensity during prenatal exercise. CONCLUSION: Research is
      needed to determine the upper limits of exercise frequency and intensity for
      pregnant women who are already trained. Healthy women and female athletes can
      usually maintain their regular training regime once they become pregnant.

PMID- 26210537
TI  - [Mouth abnormality: to the general practitioner?].

PMID- 26210536
TI  - Loss of phosphodiesterase 10A expression is associated with progression and
      severity in Parkinson's disease.
AB  - The mechanisms underlying neurodegeneration and loss of dopaminergic signalling
      in Parkinson's disease are still only partially understood. Phosphodiesterase 10A
      (PDE10A) is a basal ganglia expressed dual substrate enzyme, which regulates cAMP
      and cGMP signalling cascades, thus having a key role in the regulation of
      dopaminergic signalling in striatal pathways, and in promoting neuronal survival.
      This study aimed to assess in vivo the availability of PDE10A in patients with
      Parkinson's disease using positron emission tomography molecular imaging with
      (11)C-IMA107, a highly selective PDE10A radioligand. We studied 24 patients with
      levodopa-treated, moderate to advanced Parkinson's disease. Their positron
      emission tomography imaging data were compared to those from a group of 12
      healthy controls. Parametric images of (11)C-IMA107 binding potential relative to
      non-displaceable binding (BPND) were generated from the dynamic (11)C-IMA107
      scans using the simplified reference tissue model with the cerebellum as the
      reference tissue. Corresponding region of interest analysis showed lower mean
      (11)C-IMA107 BPND in the caudate (P < 0.001), putamen (P < 0.001) and globus
      pallidus (P = 0.025) in patients with Parkinson's disease compared to healthy
      controls, which was confirmed with voxel-based analysis. Longer Parkinson's
      duration correlated with lower (11)C-IMA107 BPND in the caudate (r = -0.65; P =
      0.005), putamen (r = -0.51; P = 0.025), and globus pallidus (r = -0.47; P =
      0.030). Higher Unified Parkinson's Disease Rating Scale part-III motor scores
      correlated with lower (11)C-IMA107 BPND in the caudate (r = -0.54; P = 0.011),
      putamen (r = -0.48; P = 0.022), and globus pallidus (r = -0.70; P < 0.001).
      Higher Unified Dyskinesia Rating Scale scores in those Parkinson's disease with
      levodopa-induced dyskinesias (n = 12), correlated with lower (11)C-IMA107 BPND in
      the caudate (r = -0.73; P = 0.031) and putamen (r = -0.74; P = 0.031). Our
      findings demonstrate striatal and pallidal loss of PDE10A expression, which is
      associated with Parkinson's duration and severity of motor symptoms and
      complications. PDE10A is an enzyme that could be targeted with novel
      pharmacotherapy, and this may help improve dopaminergic signalling and striatal
      output, and therefore alleviate symptoms and complications of Parkinson's
      disease. 

PMID- 26210539
TI  - [Dentistry in the middle ages in the low lands 7. "Van den huve ende datter toe
      behoert"].

PMID- 26210540
TI  - [Dissertations 25 years after date 40. Treatment planning in dental practices].
AB  - In dental practices, many variations exist in the processes used in planning
      treatment, in relation not only to questions relating to the anamnesis, but also
      to examinations and treatment plans. The conceptual approach of dentists plays a
      role here. More simple treatment is planned if financial resources are limited.
      Most dentists adopt a wait-and-see approach with new patients. A smaller number
      attempts to push previous treatment policy in a radically different direction.
      Subsequent research has confirmed the variation among dentists and the role of
      conceptual approaches. In the past 25 years, the theme of quality in healthcare
      has emerged. New legislation by the government has played an important role here.
      Work is also being done in dental healthcare towards developing a quality system,
      made up of professional clinical guide-lines and measuring instruments, peer
      review of their use, and guarantees. The idea behind this is to reduce
      unexplained variations among dentists and to increase the transparency of care
      for patients. 

PMID- 26210541
TI  - [Peri-implant health in people aged 75 and over with an implant-retained
      overdenture in the mandibula].
AB  - The number of elderly patients with an implant-retained overdenture in the
      mandibula is increasing. There is, however, insufficient information on how these
      elderly people are functioning with their overdenture and on their peri--implant
      health. Therefore, a study was carried out among a group of people aged 75 and
      over who had been provided with an implant-retained overdenture in a general
      dental office, measuring their ability to manage independently, their general
      health and peri-implant health. The study revealed a high degree of ability to
      manage independently, despite the health problems affecting many over 75. The
      patients rated their prosthetic overdentures with an average grade of 8.9 +/-
      1.1. Plaque around the implant (73%) and bleeding on probing (68%) were
      frequently seen. However, progressive peri-implant bone loss was seldom seen. No
      relationship was evident between plaque-scores and the ability to manage
      independently. Except for oral hygiene instruction and/or professional cleaning
      of peri-implants, no serious interventions were necessary. It was concluded that
      this group of elderly people, provided with an implant-retained mandibular
      overdenture, are functioning well. Plaque around the implant and bleeding on
      probing are often present but progressive peri-implant bone loss is rare. 

PMID- 26210542
TI  - [The cost-effectiveness evaluation of 2 caries prevention strategies compared
      with the standard approach].
AB  - A cost-effectiveness evaluation was conducted with a randomised controlled
      clinical trial of caries prevention measures among 6-year-old children who were
      assigned to either a control group or 1 of 2 experimental groups (IPFA: 2 extra
      professionally-delivered fluoride applications per year, or NOCTP: a non
      operative caries treatment programme, like the one that was previously carried
      out in Nexo, Denmark. In order to determine the cost of the prevention of 1 DMFS
      in comparison with the control practice information on expenses incurred was
      collected for 3 years. The prevention of a single DMFS - depending on whether
      costs of dental treatment only were taken into consideration or also other social
      costs - were, in the IPFA programme, 269 and 1,369 euro respectively and, in the
      NOCTP programme, 30 and 100 euro respectively. On the basis of these results, it
      can be concluded that from both a dental and cost-effective perspective the NOCTP
      programme produces the most favourable results. Following the NOCTP strategy -
      during the 3-year period - just like following the IPFA approach was, however,
      more expensive than the standard approach. 

PMID- 26210543
TI  - [Endodontics in motion: new concepts, materials and techniques 1. Hydraulic
      Calcium Silicate Cements].
AB  - Hydraulic Calcium Silicate Cements (HCSCs) constitute a group of materials that
      have become increasingly popular in endodontics since the introduction of Mineral
      Trioxide Aggregate (MTA) in the 1990s. MTA is Portland cement to which bismuth
      oxide has been added to increase its radiopacity. The most important property of
      MTA is its capacity to set in water or a humid environment. However, MTA also has
      important limitations, for example, it's difficult to work with and can discolour
      teeth. Recently, numerous products based on HCSC chemistry, which can be
      considered as modifications of MTA intended to reduce its limitations, have
      become available on the market. Despite their potential advantages, all of these
      materials have their own specific limitations that are currently insufficiently
      known and investigated. 

PMID- 26210544
TI  - [Experimental evidence on the role of different types unsaturated fats in the
      diet on ageing].
AB  - Nutrition has been largely related to the physiological ageing process. Several
      nutrients, such as certain types of dietary fat and various antioxidants have
      been shown to have positive effects on age-related diseases. The type of dietary
      fat affects mitochondrial structure and function, as well as its susceptibility
      to oxidative stress, all factors involved in ageing. The present review aims to
      summarise the studies conducted by our research group in the past 10 years, using
      virgin olive oil, sunflower oil, or fish oil as a source of unsaturated fat diet
      relative to a rat model of ageing. 

PMID- 26210545
TI  - Effect of minimizing amount of template by addition of macromolecular crowding
      agent on preparation of molecularly imprinted monolith.
AB  - One of the main challenges in the preparation of molecularly imprinted polymers
      (MIPs) is the substantial initial amount of template needed because of the
      requirement of high load capacities for most applications. A new strategy of
      macromolecular crowding was suggested to solve this problem by reducing the
      amount of template in the polymerization recipe. In a ternary porogenic system of
      polystyrene (PS) (crowding agent), tetrahydrofuran, and toluene, an imprinted
      monolithic column with high porosity and good permeability was synthesized using
      a mixture of ellagic acid (template), acrylamide, and ethylene glycol
      dimethacrylate. The effect of polymerization factors, including monomer-template
      molar ratio and the molecular weight and concentration of PS, on the imprinting
      effect of the resulting MIP monoliths was systematically investigated. At a high
      ratio of monomer-template (120:1), the greatest imprinting factor of 32.4 was
      obtained on the MIP monolith with the aid of macromolecular crowding agent. The
      PS-based imprinted monolith had imprinting even at the extremely high ratio of
      functional monomer to template of 1510:1. Furthermore, an off-line solid-phase
      extraction based on the ground MIP was conducted, and the purification recovery
      of ellagic acid from pomegranate-rind extract was up to 80 %. In conclusion, this
      approach based on macromolecular crowding is simple, and is especially valuable
      for those applications of MIP preparation for which a rare template is used. 

PMID- 26210546
TI  - Surface plasmon resonance-based methodology for anti-adalimumab antibody
      identification and kinetic characterization.
AB  - Adalimumab (ADA) is a TNF-alpha blocker drug antibody fully humanized and thus
      indistinguishable in structure and function from natural human IgG1, used in the
      juvenile idiopathic arthritis (JIA) treatment. Immunogenicity against the drug
      has been frequently detected in treated patients, and the presence of anti-ADA
      antibodies is correlated to treatment failure or lower clinical remission.
      Herein, we measured by surface plasmon resonance (SPR) both the binding and the
      affinity of anti-ADA antibodies to the ADA-immobilized biosensor. The binding of
      anti-ADA antibodies was evaluated by testing sera from ADA-treated patients (n =
      30), untreated patients (n = 9), and healthy donors (n = 20) in the SPR
      biosensor. The optimal cut-off point was defined using the receiver operating
      characteristic curve (ROC-curve) analysis with 79 % (60.28 to 92.01 %, 95 % CI)
      sensitivity, 99 % (88.06 to 100.0 %, 95 % CI) specificity, and a positive
      likelihood ratio of 23. The area under the curve was 0.9298 (p < 0.0001). The
      apparent affinity of anti-ADA antibodies from pediatric patients' sera was
      measured, analyzing the interaction of anti-drug antibodies using whole sera,
      enriched IgG fractions, and isolated anti-ADA antibodies. The immobilized drug
      ADA interacted with purified antibodies at low affinities (10(-6) M > K D > 10(
      9) M). Graphical Abstract Adalimumab immobilized on the biosensor chip surface
      detects specific anti-drug antibodies in treated patients' sera. 

PMID- 26210547
TI  - HMME combined with green light-emitting diode irradiation results in efficient
      apoptosis on human tongue squamous cell carcinoma.
AB  - Hematoporphyrin monomethyl ether (HMME) is a novel and promising porphyrin
      related photosensitizer for photodynamic therapy (PDT). This study aimed to
      investigate the efficacy and potential mechanism of HMME-PDT under irradiation of
      green light-emitting diode (LED) with wavelength of 530 +/- 20 nm in treating
      human tongue squamous cell carcinoma Tca8113 cells in vitro. The HMME
      concentrations were 1.25, 2.5, and 5 MUg/ml while the energy densities were 0.6,
      1.2, 1.8, 2.4, and 3.0 J/cm(2). MTT assay demonstrated that HMME-PDT
      significantly inhibited the proliferation of Tca8113 cells, and the cytotoxicity
      was improved with increased HMME concentration and light intensity. The amount of
      cells decreased significantly and the morphology of cells changed drastically
      after HMME-PDT. Flow cytometry analysis revealed that HMME-PDT induced both
      apoptosis and necrosis, but apoptosis was the main form of cell death. Apoptotic
      morphology was confirmed by Hoechst 33342 staining. Laser scanning confocal
      microscopy observation showed that HMME was mainly localized in mitochondria. The
      production of intracellular reactive oxygen species increased remarkably after
      PDT treatment, and both sodium azide (the singlet oxygen quencher) and D-mannitol
      (the hydroxyl radical scavenger) could protect Tca8113 cells from death induced
      by HMME-PDT. Additionally, the activity of caspase-3 also increased markedly in
      treated groups, and the cell death could be rescued by a reversible inhibitor (Ac
      DEVD-CHO) of caspase-3. These results demonstrated that HMME combined with green
      LED significantly induced apoptosis of Tca8113 cells, suggesting that HMME-PDT
      using green LED might be a potential therapeutic strategy for human tongue
      squamous cell carcinoma. 

PMID- 26210548
TI  - The effect of water on the mechanical properties of soluble and insoluble ceramic
      cements.
AB  - Ceramic cements are good candidates for the stabilization of fractured bone due
      to their potential ease of application and biological advantages. New
      formulations of ceramic cements have been tested for their mechanical properties,
      including strength, stiffness, toughness and durability. The changes in the
      mechanical properties of a soluble cement (calcium sulfate) upon water-saturation
      (saturation) was reported in our previous study, highlighting the need to test
      ceramic cements using saturated samples. It is not clear if the changes in the
      mechanical properties of ceramic cements are exclusive to soluble cements.
      Therefore the aim of the present study was to observe the changes in the
      mechanical properties of soluble and insoluble ceramic cements upon saturation. A
      cement with high solubility (calcium sulfate dihydrate, CSD) and a cement with
      low solubility (dicalcium phosphate dihydrate, DCPD) were tested. Three-point
      bending tests were performed on four different groups of: saturated CSD, non
      saturated CSD, saturated DCPD, and non-saturated DCPD samples. X-ray diffraction
      analysis and scanning electron microscopy were also performed on a sample from
      each group. Flexural strength, effective flexural modulus and flexural strain at
      maximum stress, lattice volume, and crystal sizes and shape were compared,
      independently, between saturated and non-saturated groups of CSD and DCPD.
      Although material dissolution did not occur in all cases, all calculated
      mechanical properties decreased significantly in both CSD and DCPD upon
      saturation. The results indicate that the reductions in the mechanical properties
      of saturated ceramic cements are not dependent on the solubility of a ceramic
      cement. The outcome raised the importance of testing any implantable ceramic
      cements in saturated condition to estimate its in vivo mechanical properties. 

PMID- 26210549
TI  - Ti-6Al-4V triply periodic minimal surface structures for bone implants fabricated
      via selective laser melting.
AB  - Triply periodic minimal surface (TPMS) structures have already been shown to be a
      versatile source of biomorphic scaffold designs. Therefore, in this work, Ti-6Al
      4V Gyroid and Diamond TPMS lattices having an interconnected high porosity of 80
      95% and pore sizes in the range of 560-1600 MUm and 480-1450 MUm respectively
      were manufactured by selective laser melting (SLM) for bone implants. The
      manufacturability, microstructure and mechanical properties of the Ti-6Al-4V TPMS
      lattices were evaluated. Comparison between 3D micro-CT reconstructed models and
      original CAD models of the Ti-6Al-4V TPMS lattices shows excellent reproduction
      of the designs. The as-built Ti-6Al-4V struts exhibit the microstructure of
      columnar grains filled with very fine and orthogonally oriented alpha'
      martensitic laths with the width of 100-300 nm and have the microhardness of 4.01
      +/- 0.34 GPa. After heat treatment at 680 degrees C for 4h, the alpha' martensite
      was converted to a mixture of alpha and beta, in which the alpha phase being the
      dominant fraction is present as fine laths with the width of 500-800 nm and
      separated by a small amount of narrow, interphase regions of dark beta phase.
      Also, the microhardness is decreased to 3.71 +/- 0.35 GPa due to the coarsening
      of the microstructure. The 80-95% porosity TPMS lattices exhibit a comparable
      porosity with trabecular bone, and the modulus is in the range of 0.12-1.25 GPa
      and thus can be adjusted to the modulus of trabecular bone. At the same range of
      porosity of 5-10%, the moduli of cortical bone and of the Ti-6Al-4V TPMS lattices
      are in a similar range. Therefore, the modulus and porosity of Ti-6Al-4V TPMS
      lattices can be tailored to the levels of human bones and thus reduce or avoid
      "stress shielding" and increase longevity of implants. Due to the biomorphic
      designs, and high interconnected porosity and stiffness comparable to human
      bones, SLM-made Ti-6Al-4V TPMS lattices can be a promising material for load
      bearing bone implants.

PMID- 26210552
TI  - JoPAN: What's Old and What's New!

PMID- 26210551
TI  - Risk factors for sudden cardiac death among patients with schizophrenia.
AB  - INTRODUCTION: Patients with schizophrenia suffer from excessive premature
      mortality, and sudden cardiac death (SCD) is receiving growing attention as a
      potential cause. AIM: The present study investigated the incidence of SCD and its
      risk factors in a large schizophrenia cohort. METHODS: We enrolled a consecutive
      series of 8264 patients diagnosed with schizophrenia (according to DSM-III-R and
      DSM-IV criteria) who were admitted to a psychiatric center in northern Taiwan
      from January 1, 1985 through December 31, 2008. By linking with national
      mortality database, 64 cases of SCD were identified. The standardized mortality
      ratio (SMR) for SCD was estimated. The cases were matched with controls randomly
      selected using risk-set sampling in a 1:2 ratio. A standardized chart review
      process was used to collect socio-demographic and clinical characteristics and
      the prescribed drugs for each study subject. Multivariate conditional logistic
      regression analysis was used to identify correlates of SCD at the index admission
      and the latest admission. RESULTS: The SMR for SCD was 4.5. For the clinical
      profiles at the index admission, physical disease (adjusted risk ratio
      [aRR]=2.91, P<.01) and aggressive behaviors (aRR=3.99, P<.01) were associated
      with the risk of SCD. Regarding the latest admission, electrocardiographic
      abnormalities (aRR=5.46, P<.05) and administration of first-generation
      antipsychotics (aRR=5.13, P<.01) elevated the risk for SCD. Consistently,
      aggressive behaviors (aRR=3.26, P<.05) were associated with increased risk as
      well. CONCLUSIONS: Apart from cardiovascular profiles and antipsychotics,
      physical aggression is a crucial risk factor that deserves ongoing work for
      clarifying the mechanisms mediating SCD in schizophrenia.

PMID- 26210553
TI  - Twenty-Five Years in the Blink of an Eye: Guest Editorial.

PMID- 26210550
TI  - Decreased synaptic and mitochondrial density in the postmortem anterior cingulate
      cortex in schizophrenia.
AB  - Schizophrenia (SZ) is a mental illness characterized by psychosis, negative
      symptoms, and cognitive deficits. The anterior cingulate cortex (ACC), a
      structurally and functionally diverse region, is one of several brain regions
      that is abnormal in SZ. The present study compared synaptic organization and
      mitochondrial number and morphology in postmortem ACC in SZ versus normal control
      (NC). Total synaptic density in the combined ACC was decreased in SZ, to 72% of
      normal controls (NCs), due to selective decreases in axospinous synapses, both
      asymmetric (excitatory) and symmetric (inhibitory). These changes were present in
      layers 3 and 5/6. The density of mitochondria in all axon terminals combined in
      SZ was decreased to 64% of NC. In layer 3, mitochondrial density was decreased
      only in terminals forming asymmetric synapses with spines, while in layers 5/6
      mitochondrial density was decreased in terminals forming symmetric synapses with
      spines and dendrites. The proportion of terminals making symmetric synapses that
      contained mitochondria was significantly lower in SZ than in NCs, especially for
      symmetric axospinous synapses. The number of mitochondria per neuronal somata was
      decreased in the ACC in SZ compared to NCs; this finding was present in layers 5
      6. The size of mitochondria in neuronal somata and throughout the neuropil was
      similar in SZ and NCs. Our results, though preliminary, are well supported by the
      literature, and support an anatomical substrate for some of the altered executive
      functions found in SZ. 

PMID- 26210554
TI  - Statistical Analysis of PACU Fast-Tracking Bypass.

PMID- 26210555
TI  - Response to Letter to the Editor.

PMID- 26210556
TI  - Is Promethazine 6.25 mg Intravenous Dose Really Ideal to Treat Postoperative
      Nausea and Vomiting?

PMID- 26210557
TI  - Response to Letter to the Editor.

PMID- 26210558
TI  - Postoperative Discomfort After Abdominal Surgery: An Observational Study.
AB  - PURPOSE: Patients who have surgery may experience distress in the following days.
      Although postoperative distress is a common experience, few studies have analyzed
      these patient complaints in-depth. The purpose of the present study was to
      analyze the potential causes of patients' discomfort after abdominal surgery.
      DESIGN: This was a prospective and observational study. METHODS: Patients (N =
      131) were asked to rate their discomfort twice using a list of nine items in the
      first 6 to 8 hours after surgery and at 24 hours after its completion.
      Participants were asked to score intensity from 0 (absent) to 10 (unbearable).
      FINDINGS: The main causes of discomfort at 24 hours were pain (82%), movement
      restriction (79%), and dry mouth (70%). These items also had the highest scores
      (by gender, women scored higher than did men in insomnia, dry mouth, and
      abdominal distension). No significant differences were observed between patients
      who had undergone open or laparoscopic surgery. CONCLUSION: It was concluded that
      pain, movement restriction, and dry mouth were the most disturbing causes of
      discomfort. Therefore, symptoms other than pain should be considered to improve
      the well-being of patients after abdominal surgery.

PMID- 26210559
TI  - Patients' Perceptions of Quality of Care During the Perioperative Procedure.
AB  - PURPOSE: To describe patients' perceptions of quality of care during the
      perioperative period and to identify areas for quality improvement. DESIGN: A
      cross-sectional descriptive survey design was used. METHODS: The data were
      collected (N = 170) using a questionnaire for perioperative care. The methods
      were descriptive statistics, reported as percentages, and a manifest content
      analysis of the free text. FINDING: The areas identified for improvement were
      information and participation. The participants lacked knowledge, preferred to
      hand over decision making to the hospital staff, and indicated that having
      personalized information about the surgery and perioperative period was
      important. However, too detailed information before surgery could cause increased
      anxiety. CONCLUSIONS: This study indicates that participation and information
      needs in perioperative settings seem to be situation specific. In addition, these
      needs seem to be personal and surgery specific. Further studies are required to
      clarify the differences in the satisfaction and quality of care between groups of
      patients in the perioperative context.

PMID- 26210560
TI  - Parental Satisfaction With Pediatric Preoperative Assessment and Education in a
      Presurgical Care Center.
AB  - PURPOSE: The aim of this study was to evaluate parental satisfaction with
      preoperative assessment and education in a pediatric presurgical care center
      (PSCC) as well as parental use of a computer instructional video, EMMI, which is
      a product of Emmi Solutions (Chicago, IL), a health information company for
      patients. DESIGN: A prospective, exploratory, comparative, and correlational
      descriptive design was implemented. METHODS: A 23-item questionnaire was
      completed by 542 parents or legal guardians at the end of their child's PSCC
      visit. FINDINGS: Very high overall satisfaction was seen with the visit. Highest
      overall satisfaction was seen related to nurse practitioner and registered nurse
      behaviors and lowest satisfaction to operational aspects. CONCLUSIONS: This study
      validates parents' perceptions of the high value of nurses' explanations, respect
      shown, and response to questions during preoperative assessment of the child and
      education of the family anticipating surgery. Identification of less satisfying
      aspects of the presurgical experience provides opportunities for improvement.

PMID- 26210561
TI  - Implementation of a Phase I Caregiver Visitation Program for a Specialized
      Pediatric Population.
AB  - Phase I caregiver visitation practice has been endorsed and encouraged by the
      American Society of PeriAnesthesia Nurses, yet implementation has not been
      widespread. Literature has described benefits of visitation for patients and
      their caregivers. This article reports on a Phase I caregiver visitation program
      at a specialty care hospital. The steps of implementation and guidelines for both
      the health care team and the patient's caregivers are outlined. Visitation is
      recognized as promoting patient safety during Phase I recovery. A discussion of
      additional benefits and obstacles is addressed. 

PMID- 26210562
TI  - Lipid Emulsion in Treatment of Local Anesthetic Toxicity.
AB  - Epidural, spinal, regional, local, and intravenous administration of local
      anesthetics (LAs) is a cornerstone of anesthetic practice. LA toxicity is a grave
      consequence that is of great significance to anesthesia providers. Outcomes of LA
      toxicity range from inconvenient symptoms such as tinnitus, twitching, and
      hypotension to seizures; cardiovascular or respiratory collapse; and death. Lipid
      emulsion has emerged as a potential "magic bullet" in treating LA toxicity. This
      literature review provides background information and proposed mechanisms of
      action for LAs and lipid emulsion as well as animal experiments and a case report
      that speak to the effectiveness of lipid emulsion in the face of LA toxicity. 

PMID- 26210563
TI  - Local Anesthesia Toxicity and Lipid Rescue.
AB  - Regional anesthesia as a treatment modality for the control of surgical pain has
      been in practice since the late 1880s with the introduction of cocaine. The use
      of lipid emulsion therapy as an emerging treatment for the rare but life
      threatening development of local anesthesia systemic toxicity (LAST) has been in
      the animal literature for approximately 20 years, and case reports have
      documented successful results with this treatment in humans. The perianesthesia
      nurse has a significant role in the assessment, communication with the anesthesia
      care provider, and the emergent management of the patient experiencing LAST.
      Using a fictitious case study of a patient with LAST, the conduction of sensory
      information will be reviewed. The pharmacologic characteristics of local
      anesthetics will be presented, and the evidence-based practice recommendations
      for the prevention, monitoring, and treatment will be provided. 

PMID- 26210564
TI  - Medical Device-Related Pressure Ulcers and Intensive Care Patients.

PMID- 26210565
TI  - Low-Dose Ketamine Infusions for Postoperative Pain in Opioid-Tolerant Orthopaedic
      Spine Patients.

PMID- 26210566
TI  - The Leadership Relationship. Part II: Essential Elements for a Healthy
      Relationship.

PMID- 26210567
TI  - Alarm Fatigue: Are You Tuning Out?

PMID- 26210568
TI  - The Culture of Accommodation: (Am I Paid for Hire?).

PMID- 26210569
TI  - Pharmacological Management of Perioperative Shivering.

PMID- 26210570
TI  - Documentation Tips.

PMID- 26210571
TI  - What They Don't Know Can Hurt Them: Risky Analgesic Use in Children.

PMID- 26210572
TI  - A Trip Down Memory Lane: From the Recovery Room to PACU: Guest Editorial.

PMID- 26210573
TI  - A Meta-analysis of Transcranial Direct Current Stimulation Studies Examining the
      Reliability of Effects on Language Measures.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is a brain stimulation
      technique used to examine causal relationships between brain regions and
      cognitive functions. The effects from tDCS are complex, and the extent to which
      stimulation reliably affects different cognitive domains is not fully understood
      and continues to be debated. OBJECTIVE/HYPOTHESIS: To conduct a meta-analysis of
      studies examining the effects of single-session anodal tDCS on language. METHODS:
      The meta-analysis examined the behavioral results from eleven experiments of
      single-session anodal tDCS and language processing in healthy adults. The means
      and standard deviations of the outcome measures were extracted from each
      experiment and entered into the meta-analyses. In the first analysis, we examined
      the effects of single-session tDCS across all language studies. Next, a series of
      sub-analyses examined the effects of tDCS on specific tasks and stimulation
      protocols. RESULTS: There was a significant effect from anodal single-session
      tDCS in healthy adults compared to sham (P = 0.001) across all language measures.
      Next, we found significant effects on specific stimulation protocols (e.g.,
      offline measures, P = 0.002), as well as specific tasks and electrode montages
      (e.g., verbal fluency measures and left prefrontal cortex, P = 0.035).
      CONCLUSIONS: The results indicate that single-session tDCS produces significant
      and reliable effects on language measures in healthy adults.

PMID- 26210574
TI  - Alginate micro-encapsulation of mesenchymal stromal cells enhances modulation of
      the neuro-inflammatory response.
AB  - BACKGROUND AIMS: Modulation of inflammation after brain trauma is a key
      therapeutic goal aimed at limiting the consequences of the subsequent injury
      cascade. Mesenchymal stromal cells (MSCs) have been demonstrated to dynamically
      regulate the inflammatory environment in several tissue systems, including the
      central nervous system. There has been limited success, however, with the use of
      direct implantation of cells in the brain caused by low viability and engraftment
      at the injury site. To circumvent this, we encapsulated MSCs in alginate
      microspheres and evaluated the ability of these encapsulated MSCs to attenuate
      inflammation in rat organotypic hippocampal slice cultures (OHSC). METHODS: OHSC
      were administered lipopolysaccharide to induce inflammation and immediately co
      cultured with encapsulated or monolayer human MSCs. After 24 h, culture media was
      assayed for the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha)
      produced by OHSC, as well as MSC-produced trophic mediators. RESULTS:
      Encapsulated MSCs reduced TNF-alpha more effectively than did monolayer MSCs.
      Additionally, there was a strong correlation between increased prostaglandin E2
      (PGE2) and reduction of TNF-alpha. In contrast to monolayer MSCs, inflammatory
      signals were not required to stimulate PGE2 production by encapsulated MSCs.
      Further encapsulation-stimulated changes were revealed in a multiplex panel
      analyzing 27 MSC-produced cytokines and growth factors, from which additional
      mediators with strong correlations to TNF-alpha levels were identified.
      CONCLUSIONS: These results suggest that alginate encapsulation of MSCs may not
      only provide an improved delivery vehicle for transplantation but may also
      enhance MSC therapeutic benefit for treating neuro-inflammation.

PMID- 26210575
TI  - Multidisciplinary Management of Locally Advanced Rectal Cancer--An Evolving
      Landscape?
AB  - For many years, the multidisciplinary approach of neoadjuvant radiotherapy with
      or without concurrent chemotherapy followed by total mesorectal excision and
      adjuvant fluoropyrimidine chemotherapy has remained the accepted standard
      management for locally advanced rectal cancers. Over this time period, many new
      systemic treatment options have become available, including: additional
      chemotherapeutic agents (oxaliplatin) and targeted therapies (vascular
      endothelial growth factor and epidermal growth factor receptor inhibitors), which
      can be added to neoadjuvant and adjuvant regimens or given in combination with
      radiotherapy as radio-sensitizing agents. Here we review the current literature,
      examining emerging data related to the impact of multiple modifications to the
      standard approach, including the role of neoadjuvant chemotherapy, the addition
      of new agents to standard chemoradiation, and postoperative fluoropyrimidine
      based treatment, the optimal timing of surgery, and nonoperative approaches to
      the management of locally advanced rectal cancers. 

PMID- 26210577
TI  - Inhibition of spinal 5-HT3R reverted diabetes-induced mechanical hypersensitivity
      in a GABAAR-mediated neurotransmission-dependent manner.
AB  - Spinal 5-HT3 receptor (5-HT3R) has been implicated in chronic pain development.
      The extent to which 5-HT3R contributes to spinal sensitization and diabetic
      neuropathic pain (DNP) remains elusive and the mechanisms subserving the effects
      of 5-HT3R activation on spinal pain processing during chronic pain are still
      unclear. In this study, we evaluated the contribution of spinal 5-HT3R to pain
      facilitation and spinal sensitization during DNP, exploiting the role of GABAAR
      mediated neurotransmission and glial activation in the effects elicited by
      intrathecal administration of a 5-HT3R antagonist. Mechanical nociception was
      evaluated by paw pressure test in streptozotocin (STZ)-diabetic and control rats
      after intrathecal (i.t.) administration of a 5-HT3R antagonist (Y25130). The
      spinal activation of extracellular signal-regulated kinases (ERKs) pathway and
      the expression of 5-HT3R, glial fibrillary acidic protein (GFAP; marker of
      astroglia activation) and ionized calcium binding adaptor molecule 1 (IBA-1;
      marker of microglia activation) were evaluated at the peak maximum effect of
      Y25130. The involvement of GABAAR-mediated neurotransmission in the behavioral
      pain effect of Y25130, was assessed in STZ-diabetic animals receiving i.t.
      administrations of muscimol (GABAAR agonist). Intrathecal administration of
      Y25130 reverted mechanical hyperalgesia and decreased the activation of ERKs in
      STZ-diabetic rats, while no effects were observed in control animals. The spinal
      activation of GABAAR by i.t. administration of muscimol abolished Y25130-driven
      antinociception. The expression of IBA-1, GFAP and 5-HT3R was unaltered by
      treatment. These findings point to a GABA-mediated pronociceptive role of spinal
      5-HT3R during DNP. 

PMID- 26210576
TI  - A magnetoencephalography study of multi-modal processing of pain anticipation in
      primary sensory cortices.
AB  - Pain anticipation plays a critical role in pain chronification and results in
      disability due to pain avoidance. It is important to understand how different
      sensory modalities (auditory, visual or tactile) may influence pain anticipation
      as different strategies could be applied to mitigate anticipatory phenomena and
      chronification. In this study, using a countdown paradigm, we evaluated with
      magnetoencephalography the neural networks associated with pain anticipation
      elicited by different sensory modalities in normal volunteers. When encountered
      with well-established cues that signaled pain, visual and somatosensory cortices
      engaged the pain neuromatrix areas early during the countdown process, whereas
      the auditory cortex displayed delayed processing. In addition, during pain
      anticipation, the visual cortex displayed independent processing capabilities
      after learning the contextual meaning of cues from associative and limbic areas.
      Interestingly, cross-modal activation was also evident and strong when visual and
      tactile cues signaled upcoming pain. Dorsolateral prefrontal cortex and mid
      cingulate cortex showed significant activity during pain anticipation regardless
      of modality. Our results show pain anticipation is processed with great time
      efficiency by a highly specialized and hierarchical network. The highest degree
      of higher-order processing is modulated by context (pain) rather than content
      (modality) and rests within the associative limbic regions, corroborating their
      intrinsic role in chronification. 

PMID- 26210578
TI  - Altered inhibition in the hippocampal neural networks after spreading depression.
AB  - Prolonged neuronal depression after spreading depression (SD) is followed by a
      late cellular and synaptic hyperexcitability. Intra- and extracellular recordings
      of bioelectrical activities were performed in the rodent hippocampus to
      investigate the role of gamma-aminobutyric acid (GABA)-mediated inhibition in the
      late hyperexcitable state of SD. The effect of KCl-induced negative DC potential
      shifts was investigated on extracellularly recorded paired-pulse depression (PPD)
      and bicuculline-induced afterdischarges as well as intracellularly recorded
      inhibitory post synaptic potentials (IPSPs) in the hippocampal CA1 area. The
      results revealed that SD decreased the degree of PPD, enhanced the number and
      duration of bicuculline-induced afterdischarges, and reduced the amplitude and
      duration of IPSPs. Application of low concentrations of bicuculline before the
      induction of SD enhanced the inhibitory effect of SD on IPSPs. Data indicate the
      contribution of GABA-mediated inhibition to SD-induced delayed hyperexcitability.
      Modulation of GABA function in the late hyperexcitability phase of SD may play a
      role in therapeutic management of SD-related neurological disorders. 

PMID- 26210579
TI  - alpha6-Containing nicotinic acetylcholine receptors in midbrain dopamine neurons
      are poised to govern dopamine-mediated behaviors and synaptic plasticity.
AB  - Acetylcholine (ACh) acts through nicotinic and muscarinic ACh receptors in the
      ventral midbrain and striatal areas to influence dopamine (DA) transmission. This
      cholinergic control of DA transmission is important for processes such as
      attention and motivated behavior, and is manipulated by nicotine in tobacco
      products. Identifying and characterizing the key ACh receptors involved in
      cholinergic control of DA transmission could lead to small molecule therapeutics
      for treating disorders involving attention, addiction, Parkinson's disease, and
      schizophrenia. alpha6-Containing nicotinic acetylcholine receptors (nAChRs) are
      highly and specifically expressed in midbrain DA neurons, making them an
      attractive drug target. Here, we used genetic, pharmacological, behavioral, and
      biophysical approaches to study this nAChR subtype. For many experiments, we used
      mice expressing mutant alpha6 nAChRs ("alpha6L9S" mice) that increase the
      sensitivity of these receptors to agonists such as ACh and nicotine. Taking
      advantage of a simple behavioral phenotype exhibited by alpha6L9S mice, we
      compared the ability of full versus partial alpha6(*) nAChR agonists to activate
      alpha6(*) nAChRs in vivo. Using local infusions of both agonists and antagonists
      into the brain, we demonstrate that neurons and nAChRs in the midbrain are
      sufficient to account for this behavioral response. To complement these
      behavioral studies, we studied the ability of in vivo alpha6(*) nAChR activation
      to support plasticity changes in midbrain DA neurons that are relevant to
      behavioral sensitization and addiction. By coupling local infusion of drugs and
      brain slice patch-clamp electrophysiology, we show that activating alpha6(*)
      nAChRs in midbrain DA areas is sufficient to enhance glutamatergic transmission
      in ventral tegmental area (VTA) DA neurons. Together, these results from in vivo
      studies strongly suggest that alpha6(*) nAChRs expressed by VTA DA neurons are
      positioned to strongly influence both DA-mediated behaviors and the induction of
      synaptic plasticity by nicotine. 

PMID- 26210580
TI  - Vitamin D regulates tyrosine hydroxylase expression: N-cadherin a possible
      mediator.
AB  - Vitamin D is a neuroactive steroid. Its genomic actions are mediated via the
      active form of vitamin D, 1,25(OH)2D3, binding to the vitamin D receptor (VDR).
      The VDR emerges in the rat mesencephalon at embryonic day 12, representing the
      peak period of dopaminergic cell birth. Our prior studies reveal that
      developmental vitamin D (DVD)-deficiency alters the ontogeny of dopaminergic
      neurons in the developing mesencephalon. There is also consistent evidence from
      others that 1,25(OH)2D3 promotes the survival of dopaminergic neurons in models
      of dopaminergic toxicity. In both developmental and toxicological studies it has
      been proposed that 1,25(OH)2D3 may modulate the differentiation and maturation of
      dopaminergic neurons; however, to date there is lack of direct evidence. The aim
      of the current study is to investigate this both in vitro using a human SH-SY5Y
      cell line transfected with rodent VDR and in vivo using a DVD-deficient model.
      Here we show that in VDR-expressing SH-SY5Y cells, 1,25(OH)2D3 significantly
      increased production of tyrosine hydroxylase (TH), the rate-limiting enzyme in
      dopamine synthesis. This effect was dose- and time-dependent, but was not due to
      an increase in TH-positive cell number, nor was it due to the production of
      trophic survival factors for dopamine neurons such as glial-derived neurotrophic
      factor (GDNF). In accordance with 1,25(OH)2D3's anti-proliferative actions in the
      brain, 1,25(OH)2D3 reduced the percentage of dividing cells from approximately 15
      10%. Given the recently reported role of N-cadherin in the direct differentiation
      of dopaminergic neurons, we examined here whether it may be elevated by
      1,25(OH)2D3. We confirmed this in vitro and more importantly, we showed DVD
      deficiency decreases N-cadherin expression in the embryonic mesencephalon. In
      summary, in our in vitro model we have shown 1,25(OH)2D3 increases TH expression,
      decreases proliferation and elevates N-cadherin, a potential factor that mediates
      these processes. Accordingly all of these findings are reversed in the developing
      brain in our DVD-deficiency model. Remarkably our findings in the DVD-deficiency
      model phenocopy those found in a recent model where N-cadherin was regionally
      ablated from the mesencephalon. This study has, for the first time, shown that
      vitamin D directly modulates TH expression and strongly suggests N-cadherin may
      be a plausible mediator of this process both in vitro and in vivo. Our findings
      may help to explain epidemiological data linking DVD deficiency with
      schizophrenia. 

PMID- 26210581
TI  - Application of multiplexing technology to the analysis of the intrathecally
      released immunoglobulins against B. burgdorferi antigens in neuroborreliosis.
AB  - Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused
      by the tick-borne spirochete Borrelia burgdorferi. The presence of B. burgdorferi
      specific antibodies in cerebrospinal fluid (CSF), with evidence of intrathecal
      production, is the traditional diagnostic standard, although has limitations it
      such as low sensitivity in the very early phase. In the current study, 27
      patients with possible neuroborreliosis suffered from clinically defined
      Bannwarth syndrome. The control group (CON) consisted of 6 patients. The analyses
      included function of the blood-CSF barrier (QAlb) as well as intrathecal
      synthesis of total IgG and IgM, (QIgG, and QIgM). Multiplexing analyses of the
      specific antibodies (IgG and IgM) against B.burgdorferi antigens were performed
      with the Microgen assay (Neuried, Germany). The ASI antibodies (Antibody
      Synthesis Index) specific to particular B. burgdorferi antigens (VlsE, OspC,
      etc.) were calculated analogously as QIgG and QIgM for separate antibody. All but
      one patient with NB had pathologic ASI-IgG against B. burgdorferi (median 6.3).
      Out of 27 NB patients, 13 had measurable ASI-IgM, and all these indices were
      pathologic. None of the CON subjects had pathologic ASI in either IgG or IgM
      class. Furthermore, NB patients showed dysfunction of the blood-CSF barrier
      (average QAlb in the NB and CON groups: 13.8 and 5.6, respectively, p<0.01).
      Twenty-one of 27 NB patients had at least one positive (>1.5) IgG-ASI against
      either VlsE, p100, p58, p39, p18, or OspC, and none of these patients showed
      positive OspA-IgG-ASI. Interestingly, the NB patient with negative IgG ASI on
      ELISA had the highest p100 IgG ASI on multiplexing (270.8). Among the 13 NB
      patients with detectable IgM-ASI on ELISA, nine showed measurable IgM-ASI against
      at least one antigen; however, in one of these cases, the OspC ASI was normal
      (0.6). In addition, one subject with non-measurable IgM ASI on ELISA had highly
      pathologic (19.7) index for OspC B. g. on multiplexing. The control subjects with
      measurable ASI-IgG on ELISA (two cases) had measurable, but normal, indices for
      VlsE in the IgG class also on multiplexing. None of the control subjects had
      measurable indices for any of the antigens in the IgM class. The simultaneous
      analysis of a panel of antibodies against different B. burgdorferi antigens makes
      multiplexing technology a very interesting supplement to the classic ELISA by
      providing more specific, antigen-related indices to the general, antigen
      unspecific ASI. Whether this additional information proves to be diagnostically
      relevant will be certainly a matter of further studies. 

PMID- 26210582
TI  - Effect of fringe-artifact correction on sub-tomogram averaging from Zernike phase
      plate cryo-TEM.
AB  - Zernike phase-plate (ZPP) imaging greatly increases contrast in cryo-electron
      microscopy, however fringe artifacts appear in the images. A computational de
      fringing method has been proposed, but it has not been widely employed, perhaps
      because the importance of de-fringing has not been clearly demonstrated. For
      testing purposes, we employed Zernike phase-plate imaging in a cryo-electron
      tomographic study of radial-spoke complexes attached to microtubule doublets. We
      found that the contrast enhancement by ZPP imaging made nonlinear denoising
      insensitive to the filtering parameters, such that simple low-frequency band-pass
      filtering made the same improvement in map quality. We employed sub-tomogram
      averaging, which compensates for the effect of the "missing wedge" and
      considerably improves map quality. We found that fringes (caused by the abrupt
      cut-on of the central hole in the phase plate) can lead to incorrect
      representation of a structure that is well-known from the literature. The
      expected structure was restored by amplitude scaling, as proposed in the
      literature. Our results show that de-fringing is an important part of image
      processing for cryo-electron tomography of macromolecular complexes with ZPP
      imaging. 

PMID- 26210584
TI  - Development of an ATP measurement method suitable for xenobiotic treatment
      activated sludge biomass.
AB  - Activated sludge consumes a large amount of energy to degrade a xenobiotic
      organic compound. By tracking the energy inventory of activated sludge biomass
      during the sludge's degradation of a xenobiotic, any disadvantageous effect on
      the sludge's performance caused by energy deficiency can be observed. The purpose
      of this study was to develop a reliable and accurate method for measuring the ATP
      contents of activated sludge cells that were to degrade a xenobiotic organic.
      Cell disruption and cellular ATP extraction were performed by a protocol with
      which xenobiotic degrading activated sludge biomass was washed with SDS, treated
      by Tris and TCA, and followed by bead blasting. The suspension of disrupted cells
      was filtered before the filtrate was injected into HPLC that was set at optimal
      conditions to measure the ATP concentration therein. This extraction protocol and
      HPLC measurement of ATP was evaluated for its linearity, limits of detection, and
      reproducibility. Evaluation test results reported a R(2) of 0.999 of linear fit
      of ATP concentration versus activated sludge concentration, a LOD=0.00045mg/L, a
      LOQ=0.0015mg/L for HPLC measurement of ATP, a MDL=0.46mg/g SS for ATP extraction
      protocol, and a recovery efficiency of 96.4+/-2%. This method of ATP measurement
      was simple, rapid, reliable, and was unburdened of some limitations other methods
      may have. 

PMID- 26210583
TI  - Molecular mechanism of copper-zinc superoxide dismutase activity change exposed
      to N-acetyl-L-cysteine-capped CdTe quantum dots-induced oxidative damage in mouse
      primary hepatocytes and nephrocytes.
AB  - Quantum dots (QDs) are engineered semiconductor nanocrystals with promising
      application in biomedicine, which have potential toxic effect on
      biomacromolecules by direct interaction and indirect impact in the body. In this
      work, the effect of N-acetyl-L-cysteine-capped CdTe quantum dots with
      fluorescence emission peak at 612 nm (QDs-612) on copper-zinc superoxide
      dismutase (Cu/ZnSOD) at molecular and cellular level was investigated using
      isothermal titration calorimetry, spectroscopic techniques, cell counting kit-8,
      and total SOD assay. The hydrophobic interaction between Cu/ZnSOD and QDs-612
      caused static fluorescence quenching of the protein, which was spontaneous with
      binding constant calculated to be 3.28 * 10(5) L mol(-1). The microenvironment of
      tyrosine residues, skeleton, and secondary structure of Cu/ZnSOD were changed
      with adding QDs-612. The molecular Cu/ZnSOD activity was inhibited at different
      concentrations of QDs-612 as well as the intracellular Cu/ZnSOD activity after 2
      h exposure. Compared with the cell viability of hepatocytes and nephrocytes
      (decreased markedly of the initial level) with higher concentrations of QDs-612
      in the absence of vitamin C, the cell viability of these two primary cells
      increased in the presence of vitamin C, indicating the oxidative damage induced
      by QDs-612. Therefore, the inhibition of Cu/ZnSOD activity in these two primary
      cells may be caused by the oxidative damage of massive ROS or direct interaction
      with QDs-612. This work establishes a new approach to investigate the biological
      toxicity of CdTe QDs to biomacromolecule from both molecular and cellular
      perspectives and obtains experimental evidence to thoroughly study the toxicity
      of CdTe QDs in vivo. 

PMID- 26210585
TI  - A novel fully validated LC-MS/MS method for quantification of pyridoxal-5'
      phosphate concentrations in samples of human whole blood.
AB  - Quantification of pyridoxal-5'-phosphate (PLP) in biological samples is
      challenging due to the presence of endogenous PLP in matrices used for
      preparation of calibrators and quality control samples (QCs). Hence, we have
      developed an LC-MS/MS method for accurate and precise measurement of the
      concentrations of PLP in samples (20MUL) of human whole blood that addresses this
      issue by using a surrogate matrix and minimizing the matrix effect. We used a
      surrogate matrix comprising 2% bovine serum albumin (BSA) in phosphate buffer
      saline (PBS) for making calibrators, QCs and the concentrations were adjusted to
      include the endogenous PLP concentrations in the surrogate matrix according to
      the method of standard addition. PLP was separated from the other components of
      the sample matrix using protein precipitation with trichloroacetic acid 10% w/v.
      After centrifugation, supernatant were injected directly into the LC-MS/MS
      system. Calibration curves were linear and recovery was >92%. QCs were accurate,
      precise, stable for four freeze-thaw cycles, and following storage at room
      temperature for 17h or at -80 degrees C for 3 months. There was no significant
      matrix effect using 9 different individual human blood samples. Our novel LC
      MS/MS method has satisfied all of the criteria specified in the 2012 EMEA
      guideline on bioanalytical method validation. 

PMID- 26210586
TI  - Evaluation of the matrix effect of different sample matrices for 33
      pharmaceuticals by post-column infusion.
AB  - Matrix effects that occur during quantitative measurement by liquid
      chromatography mass spectrometry specifically when using electrospray ionization
      are a widely recognized phenomenon. Sample matrix compounds affect the ionization
      process of the target analytes, lead to a low signal response, and flawed
      analytical results. How these matrix compounds directly influence the ionization
      process has not yet been completely understood. In the present study, we
      determined the matrix effect for 33 pharmaceutical substances in sample extracts
      of urine, plasma and wastewater. Most of the investigated substances were subject
      to a signal suppression effect. Only for a small subset of the compounds we
      detected a signal enhancement effect. We investigated the matrix effect profiles
      in detail to disentangle the influence of different matrices and to correlate the
      impact of specific components and groups of the analyzed extract in suppressing
      or enhancing effects in the profile. Most signal suppression effects were
      detected in the first half of the chromatographic run-time for the matrix
      extracts of urine and wastewater. The observed effects are caused by high mass
      flow of salts and other diverse matrix components that were contained in high
      concentrations in those biological matrices. We also found signal suppression in
      the matrix effect profile of plasma samples over a wide time range during the
      chromatographic separation that were associated with a high content of
      triglycerides of diverse carbohydrate chain lengths. Here, we provide a broader
      picture of how 33 substances were influenced during analysis. Our results imply
      that a high number of the investigated substances had comparable effects of
      matrix compounds, despite differences in their chemical structure. 

PMID- 26210587
TI  - Exposure to Deepwater Horizon weathered crude oil increases routine metabolic
      demand in chub mackerel, Scomber japonicus.
AB  - During the 2010 Deepwater Horizon incident, the continuous release of crude oil
      from the damaged Macondo 252 wellhead on the ocean floor contaminated surface
      water habitats for pelagic fish for more than 12weeks. The spill occurred across
      pelagic, neritic and benthic waters, impacting a variety of ecosystems. Chemical
      components of crude oil are known to disrupt cardiac function in juvenile fish,
      and here we investigate the effects of oil on the routine metabolic rate of chub
      mackerel, Scomber japonicus. Mackerel were exposed to artificially weathered
      Macondo 252 crude oil, prepared as a Water Accommodated Fraction (WAF), for 72 or
      96h. Routine metabolic rates were determined pre- and post-exposure using an
      intermittent-flow, swim tunnel respirometer. Routine energetic demand increased
      in all mackerels in response to crude oil and reached statistical significance
      relative to unexposed controls at 96h. Chemical analyses of bile from exposed
      fish revealed elevated levels of fluorescent metabolites, confirming the
      bioavailability of polycyclic aromatic hydrocarbons (PAHs) in the exposure WAF.
      The observed increase in metabolic demand is likely attributable to the
      bioenergetic costs of contaminant detoxification. These results indicate that
      short-term exposure (i.e. days) to oil has sub-lethal toxicity to mackerel and
      results in physiological stress during the active spill phase of the incident. 

PMID- 26210588
TI  - Magnetic properties of sediments in cores from the Mandovi estuary, western
      India: Inferences on provenance and pollution.
AB  - Magnetic properties of sediments were investigated in 7 gravity cores recovered
      along a transect of the Mandovi estuary, western India to understand their
      provenance and pollution. The maximum magnetic susceptibility of sediments was at
      least 6 times higher in the upper/middle estuary than in lower estuary/bay. The
      chifd% and chiARM/SIRM of sediments indicated coarse, multi-domain and pseudo
      single domain magnetic grains, resembling ore material in the upper/middle
      estuary and coarse stable single domain (SSD) to fine SSD grains in the lower
      estuary/bay. Mineralogy parameters indicated hematite and goethite-dominated
      sediments in the upper/middle estuary and magnetite-dominated sediments in the
      lower estuary/bay. Two sediment types were discernible because of deposition of
      abundant ore material in the upper/middle estuary and detrital sediment in the
      lower estuary/bay. The enrichment factor and Index of geo-accumulation of metals
      indicated significant to strong pollution with respect to Fe and Mn in sediments
      from the upper/middle estuary.

PMID- 26210590
TI  - Identification and quantification of bovine protein lactosylation sites in
      different milk products.
AB  - The microbiological safety of milk is typically guaranteed by thermal treatments,
      such as pasteurization and ultra high temperature (UHT) treatment, whereas infant
      formula (IF) is often produced at even harsher conditions including a drying
      process. Thermal treatments have raised concerns, as they may denature proteins
      and initiate protein modifications. Previous studies identified already many
      lactosylation sites in milk and showed that the lactosylation degree of some
      proteins correlates to thermal treatment conditions. Here, we studied the
      glycation degrees of 124 lactosylation sites in 28 bovine milk proteins in raw
      milk, three brands of pasteurized milk, three brands of UHT milk, and five brands
      of IF. Whereas, the glycation degree of many lactosylation sites increased from
      raw milk, to pasteurized milk, UHT milk, and IF, several modification sites
      showed a different behavior indicating that global measures do not correctly
      reflect the reactivity of distinct sites. Interestingly, the glycation degrees
      varied considerably among the brands of UHT milk and IF indicating that specific
      production processes of a company have to be considered and not only the
      classification of milk as pasteurized or UHT. Thus, proper adjustments of the
      technical processes should allow reducing the lactosylation levels in both UHT
      milk and IF. SIGNIFICANCE: It is well established that thermal treatment of milk
      triggers protein modifications, such as lactosylation of lysine residues in
      several proteins, although the extent of lactosylation has not been
      quantitatively compared for a broad panel of protein lactosylation sites among
      different commercial products. The current study extends previous reports by
      relatively quantifying 124 confirmed lactosylation sites in 28 bovine milk
      proteins including several low abundant proteins. Whereas, glycation is generally
      assumed to be an unspecific chemical reaction with the modification degrees
      depending on the protein and sugar concentrations, we could show that each
      protein and even each lactosylation site in a given protein is differently
      affected by thermal processes indicating that the global lactosylation degrees
      will not allow predicting the influence of a technical process on individual
      proteins and lactosylation sites. Additionally, we could show that brands of each
      milk product differ significantly in their glycation degrees with UHT milk brands
      for example spanning the whole range from the relatively low lactosylation degree
      of pasteurized milk to the rather high lactosylation degree of IF. Similar
      differences were obtained for IF that generally showed the highest glycation
      degree. The targeted quantification approach established and validated here will
      be useful to reveal technical processing steps that trigger individual
      lactosylation sites and thus can help to prevent such unwanted reactions. Even
      slight changes of the technical processes might allow reducing the lactosylation
      degree of milk proteins significantly without challenging the microbiological
      safety or affecting consumer behavior.

PMID- 26210589
TI  - Polycyclic aromatic hydrocarbons in surface sediment from Yangpu Bay, China:
      Distribution, sources and risk assessment.
AB  - The study investigated the occurrence of polycyclic aromatic hydrocarbons (PAHs)
      in the surface sediment from eleven sites in Yangpu Bay, China in December 2013
      (winter) and July 2014 (summer). The 16 US EPA priority PAHs were found in the
      range of 1583.2-5701.7 ng/g dry weights with an average of 3134.7 +/- 1241.3 ng/g
      in winter and ranged from 2161.8 to 4527.2 ng/g with an average of 3016.6 +/-
      748.0 ng/g in summer, respectively. The concentrations of the PAHs tended to be
      relatively high in comparison with other areas from the literatures. The
      identification using molecular indices analysis indicated that the PAHs
      originated mainly from pyrogenic and petrogenic sources in most of the sites.
      According to principle component analysis-multiple linear regression (PCA/MLR)
      for their source apportionment, the main sources of PAHs were vehicle emissions,
      petroleum products and biomass combustion. The risk assessment using
      international sediments quality guidelines and sediments quality criteria
      indicated that several PAHs, such as Nap, Flu, Phe, Ace, Acy and BghiP in most of
      the sites would potentially affect organisms in Yangpu Bay.

PMID- 26210591
TI  - Exploring the membrane proteome of the diazotropic cyanobacterium Anabaena
      PCC7120 through gel-based proteomics and in silico approaches.
AB  - This paper focuses on the gel-based membrane proteomics from diazotrophic
      cyanobacterium Anabaena PCC7120 by modifying the protocol of Hall et al. [1]. The
      bioinformatic analysis revealed that 59 (29 integral, 30 peripheral) of the 67
      proteins identified were membrane proteins. Of the 29 integral proteins, except
      Alr0834, the remaining 28 contained 1-12 transmembrane helices. Sixteen integral
      proteins harboring signal peptides (Sec/TAT/LipoP) suggest that protein targeting
      in Anabaena involves both sec-dependent and sec-independent pathways. While
      majority of photosynthesis and respiration proteins (21 of 24) were confined to
      broad pH gradient the hypothetical and unknown (12 of 13), and cell envelope
      proteins (3 of 3) preferred the narrow pH range. Of the 5 transporters and
      binding proteins, Na(+)/H(+)-exchanging protein and Alr2372 were present in
      broad, pstS1 and cmpD in narrow and cmpA was common to both pH ranges. The
      distribution of proteins across pH gradient, thus clearly indicates the
      functional and structural diversity in membrane proteome of Anabaena. It requires
      mention that protochlorophyllide oxido-reductase, Na(+)/H(+)-exchanging protein,
      All1355, Alr2055, Alr3514, Alr2903 and Alr2751 were new entries to the 2DE
      membrane protein profile of Anabaena. This study demonstrates suitability of the
      modified protocol for the study of membrane protein from filamentous
      cyanobacteria. SIGNIFICANCE: Anabaena sp. PCC7120 is used as a model organism due
      to its agriculture significance as biofertilizer, close resemblance with higher
      plant chloroplast and availability of full genome sequence. Although cytosolic
      proteome has been explored a lot membrane proteins are still understudied as they
      are notoriously difficult to display using 2-D technology. Identification and
      characterization of these proteins is therefore required to elucidate and
      understand cellular mechanisms. The purpose of this study was to develop a
      protocol suitable for membrane protein extraction from Anabaena. Additionally, by
      homology comparison or domain assignment a possible function could be ascribed to
      novel uncharacterized proteins which will serve as a useful reference for further
      detailed studies of membrane system in filamentous cyanobacteria. Resolution of
      membrane proteins ranging from least (single transmembrane helix) to highly
      hydrophobic (several transmembrane helices) one on 2D gels recommends the gel
      based approach for identification of membrane proteomics from filamentous
      cyanobacteria. This article is part of a Special Issue entitled: Proteomics in
      India.

PMID- 26210592
TI  - Label-free electrochemical DNA sensor using "click"-functionalized PEDOT
      electrodes.
AB  - Here we describe a label-free electrochemical DNA sensor based on poly(3,4
      ethylenedioxythiophene)-modified (PEDOT-modified) electrodes. An acetylene
      terminated DNA probe, complementary to a specific "Hepatitis C" virus sequence,
      was immobilized onto azido-derivatized conducting PEDOT electrodes using "click"
      chemistry. DNA hybridization was then detected by differential pulse voltammetry,
      evaluating the changes in the electrochemical properties of the polymer produced
      by the recognition event. A limit of detection of 0.13 nM was achieved using this
      highly selective PEDOT-based genosensor, without the need for labeling techniques
      or microelectrode fabrication processes. These results are promising for the
      development of label-free and reagentless DNA hybridization sensors based on
      conducting polymeric substrates. Biosensors can be easily prepared using any DNA
      sequence containing an alkyne moiety. The data presented here reveal the
      potential of this DNA sensor for diagnostic applications in the screening of
      diseases, such as "Hepatitis C", and genetic mutations.

PMID- 26210593
TI  - Micro-structured peptide surfaces for the detection of high-affinity peptide
      receptor interactions in living cells.
AB  - Peptide ligands have great potential as selective agents for diagnostic imaging
      and therapeutic targeting of human cancers. A number of high-throughput assays
      for screening potential candidate peptides have been developed. Although these
      screening assays are indispensable for the identification of peptide ligands at a
      large scale, it is crucial to validate peptide binding and selectivity for
      targeted receptors in a live-cell context. For testing high-affinity peptide
      receptor interactions in the plasma membrane of living cells, we developed cell
      resistant, micro-structured glass surfaces with high-density and high-contrast
      peptide features. Cell adhesion and recruitment of fluorescent receptors to micro
      patterned peptides in the live-cell membrane were evaluated by reflection
      interference contrast (RIC) and total internal reflection (TIRF) microscopy,
      respectively. To demonstrate both the specificity and modularity of the assay, co
      patterning of fluorescent receptors with three different immobilized micro
      structured ligands was shown: first, interaction of green fluorescent protein
      (GFP)-tagged epidermal growth factor (EGF) receptor expressed in Jurkat cells
      with immobilized EGF was detected and quantified. Second, using Jurkat cells, we
      demonstrated specific interaction of yellow fluorescent protein (YFP)-tagged
      beta3 integrin with c(RGDfK) peptide. Third, we identified indirect recruitment
      of GFP-tagged alpha5 integrin to an 11-mer peptide. In summary, our results show
      that the developed micro-structured surfaces are a useful tool for the validation
      and quantification of peptide-receptor interactions in their natural cellular
      environment. 

PMID- 26210595
TI  - Quantitation of infliximab using clonotypic peptides and selective reaction
      monitoring by LC-MS/MS.
AB  - OBJECTIVES: Although therapeutic concentrations of infliximab (chimeric IgG1
      kappa) are associated with improved clinical prognosis, clinical laboratory
      methods for monitoring are limited. Therefore, we aimed to develop a LC-MS/MS
      method to measure infliximab in serum. METHODS: Infliximab was measured using
      isotope-labeled peptides and horse IgG as a surrogate internal standard. After
      trypsin digestion, peptides were separated by reverse-phase C8 LC and detected by
      MS/MS on an ABSciex API 5000; analyte-to-internal standard peak area ratios were
      used for quantitation. Sera from patients receiving infliximab were collected at
      different time points in treatment and compared with a commercially available
      ECLIA method. RESULTS: The linear dynamic range of the assay was 1-100 MUg/mL
      (R(2)>0.998); both intra- and inter-assay imprecisions were <20%. Patients
      undergoing infliximab therapy had trough concentrations of 8.5 +/- 8.8 MUg/mL
      (mean +/- SD), which substantially increased 48-72 h after infusion (77 +/- 40
      MUg/mL), then fell after 28-32 days (15 +/- 11 MUg/mL). A comparison of LC-MS/MS
      and ECLIA methods demonstrated a slope of 0.967 (95% CI: 0.894-1.034, r=0.970).
      CONCLUSIONS: We have demonstrated the ability to quantify infliximab in patients
      using clonotypic peptides. This approach has the potential to be quickly
      adaptable to other monoclonal antibodies and to expand the availability of
      testing for this class of therapeutics in routine clinical practice.

PMID- 26210594
TI  - Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has
      Niacin Lost its Place?
AB  - Niacin is considered to be a powerful drug for the treatment of lipid and
      lipoprotein abnormalities connected with "residual cardiovascular risk", which
      persist in high-risk patients even when the target goals of LDL-C are achieved
      with statin therapy. Recent large randomized clinical studies - AIM-HIGH
      (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High
      Triglycerides) and HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to
      Reduce the Incidence of Vascular Events) - delivered some disappointing results,
      leading to the conclusion that no further benefit (decreased parameters of
      cardiovascular risk) is achieved by adding niacin to existing statin therapy in
      patients with high cardiovascular risk. Moreover, in these studies, several
      adverse effects of the treatment were observed; therefore, niacin treatment for
      hypolipidemias is not recommended. In this paper, we analyze the mechanisms
      underlying the hypolipidemic and antiatherogenic effects of niacin as well as
      some limitations of the designs of the AIM HIGH and HP2-THRIVE studies. We also
      provide the possibilities of rational usage of niacin for specific types of
      dyslipidemias.

PMID- 26210596
TI  - Ophthalmic Pathology: History, Accomplishments, Challenges, and Goals.

PMID- 26210597
TI  - Intermittent Exotropia and Accommodative Esotropia: Distinct Disorders or Two
      Ends of a Spectrum?

PMID- 26210598
TI  - Re: Chew et al.: No clinically significant association between CFH and ARMS2
      genotypes and response to nutritional supplements: AREDS report number 38
      (Ophthalmology 2014;121:2173-80).

PMID- 26210599
TI  - Author reply: To PMID 24974817.

PMID- 26210600
TI  - Re: Lepore et al.: Intravitreal bevacizumab versus laser treatment in type 1
      retinopathy of prematurity: report on fluorescein angiographic findings
      (Ophthalmology 2014;121:2212-9).

PMID- 26210601
TI  - Author reply: To PMID 25001158.

PMID- 26210602
TI  - Re: Lepore et al.: Intravitreal bevacizumab versus laser treatment in type 1
      retinopathy of prematurity: report on fluorescein angiographic findings
      (Ophthalmology 2014;121:2212-9).

PMID- 26210603
TI  - Author reply: To PMID 25001158.

PMID- 26210604
TI  - Re: Yu et al.: Releasable encircling band for primary rhegmatogenous retinal
      detachment (Ophthalmology 2014;121:2504-5).

PMID- 26210605
TI  - Author Reply.

PMID- 26210606
TI  - The effects of a priming dose of alcohol and drinking environment on snack food
      intake.
AB  - Alcohol consumption is a potential risk factor for being overweight. We aimed to
      investigate the effects of an alcohol priming dose and an alcohol-related
      environment on snacking behaviour. One hundred and fourteen social drinkers
      completed one of four experimental sessions either receiving a priming dose of
      alcohol (.6 g/kg) or soft drink in a bar-lab or a sterile lab. Participants
      provided ratings of appetite, snack urge, and alcohol urge before and after
      consuming their drinks. Participants completed an ad libitum snack taste test of
      savoury and sweet, healthy and unhealthy foods before completing the self-reports
      a final time. Appetite and snack urge increased more following alcohol
      consumption, and decreased to a lesser extent following the taste test relative
      to the soft drink. Total calories (including drink calories) consumed were
      significantly higher in the alcohol groups. There was a marginal effect of
      environment; those in the bar-lab consumed a higher proportion of unhealthy
      foods. These effects were more pronounced in those who were disinhibited. While
      alcohol may not increase food consumption per se, alcohol may acutely disrupt
      appetite signals, perhaps via processes of reward and inhibitory control,
      resulting in overall greater calorie intake. Individuals who are generally
      disinhibited may be more vulnerable to the effects of alcohol and drinking
      environments on eating behaviour.

PMID- 26210607
TI  - Diphyllobothrium sp. in Canis familiaris from the subtropical area of Argentina
      (Puerto Iguazu, Misiones).
AB  - This paper reports the first finding of Diphyllobothrium sp. eggs in Canis
      familiaris (domestic dog) from Puerto Iguazu, a subtropical city of Misiones
      province, Argentina. In 2013, two positive cases of Diphyllobothrium sp. eggs
      were detected during an annual parasitological survey of dogs. Dog feces were
      collected in vials containing 10% formalin and processed using Telemann's
      sedimentation and Sheather's flotation techniques. The two cases were detected in
      rural areas of the municipality. Since Misiones is not a part of the endemic area
      of diphyllobothriasis and given the fact that it is located in the three-border
      area of Argentina, Brazil and Paraguay, we consider this finding of great
      importance to public health. We stress the need for updating the current
      knowledge about the life cycle of these parasites considering the range of
      intermediate and definitive hosts, their zoonotic potential, and the
      epidemiological situation in non-endemic areas. 

PMID- 26210608
TI  - Sources of polycyclic aromatic hydrocarbons in sediments of the Bharalu River, a
      tributary of the River Brahmaputra in Guwahati, India.
AB  - Analysis of riverine sediments offers important information regarding
      anthropogenic activities in the adjacent watershed. In this study, we provide
      polycyclic aromatic hydrocarbon (PAH) levels, their possible sources and
      potential hazards in the Bharalu tributary of the Brahmaputra River flowing
      through Guwahati city in India. The USEPA's 16 priority PAHs were determined in
      river bank sediments during two distinct seasons viz. pre- and post-monsoon. The
      ?PAHs concentrations varied between 338 and 23,100 ng g(-1) during post-monsoon
      and between 609 and 8620 ng g(-1) during pre-monsoon. Mean benzo(a)pyrene (BaP)
      levels were between 17.8 +/- 12 and 21.9 +/- 27 ng g(-1) during post- and pre
      monsoon seasons respectively. Spatial variations were observed. Interestingly,
      bank sediment samples from the sites near the confluence of the Bharalu River
      with the Brahmaputra River were found to have maximum concentrations of PAHs
      during post-monsoon season. The profile of the PAHs was dominated by 3-, 4- and 6
      ring compounds. We estimated hazards of PAHs as RQ?PAHs, which showed seasonal
      variation: 3 times higher during post-monsoon than pre-monsoon. 3-and 4-ring PAHs
      were the major PAHs of concern. The Bharalu River sediment was found to pose
      medium to high hazards to ecosystem. The individual PAHs including Acy, Phen and
      Pyr were observed with RQ(MPCs) value >1 indicating severe hazards during post
      monsoon and pre-monsoon season. A very high percentage of coefficient of
      variation (CV) for PAHs during post-monsoon also revealed great variation in
      hazards and sources in this season. The diagnostic ratios indicated both
      petrogenic and pyrogenic origin of the PAHs. The pyrogenic contributions were
      mainly attributed to emissions from diesel, gasoline and wood combustion which
      are mainly from anthropogenic sources.

PMID- 26210609
TI  - Speciation of metals and their distribution in tropical estuarine mudflat
      sediments, southwest coast of India.
AB  - Two sediment cores collected from a mudflat sedimentary environment of Swarna
      estuary (S3) and Gurpur estuary (MF6), representing the middle estuarine region,
      Karnataka, India, were investigated to understand bioavailability of metals and
      their toxicity. The subsamples were analyzed for sand, silt, clay, organic carbon
      and total metal concentration of Aluminum (Al), Iron (Fe), Manganese (Mn), Nickel
      (Ni), Zinc (Zn), Copper (Cu), Cobalt (Co) and Chromium (Cr) at 2 cm intervals.
      Sediments (average) are relatively coarser in Gurpur estuary whereas silt, clay,
      organic carbon along with the studied metals (except Mn and Cu) is noted to be
      higher in the Swarna estuary. Significant correlations were observed of Al, Fe
      with finer sediments and most of the trace metals in both the cores indicating a
      mainly lithogenic source. Further, metal speciation analysis carried out for Fe,
      Mn, Ni, Zn, Cu, Co and Cr on selected samples of both the cores indicated that Fe
      was largely associated with the residual fraction with 93 +/- 0.5% in Gurpur and
      84 +/- 6% in Swarna estuary. The concentration of studied metals in the residual
      fraction in the sediments of Gurpur estuary was in the order Mn(90 +/- 5%)>Cr(85
      +/- 1%)>Ni(72 +/- 5%)>Zn(69 +/- 3%)>Cu(57 +/- 5%)>Co(55 +/- 2%) and; Cr(80 +/-
      7%)>Mn(77 +/- 10%)>Ni(76 +/- 7%)>Zn(67 +/- 10%)>Cu(67 +/- 10%)>Co(50 +/- 7%) in
      Swarna estuary. When the total (bulk) metals were compared with the Sediment
      Quality Values (SQV) following Screening Quick Reference Table (SQUIRT), Co
      values of both the cores fell above Apparent Effect Threshold (AET) values. When
      the sum of the average bioavailable fractions in sediments was considered, Co
      values exceeded the AET in core S3 (Swarna estuary). When the variations are
      viewed with depth, bioavailability of Mn, Ni, Cu and Co in Gurpur estuary
      indicated anthropogenic addition in recent years whereas in Swarna estuary most
      of the studied metals showed diagenetic remobilization and diffusion to the water
      column from surface sediments. Metal speciation study indicated no harm to the
      aquatic life, except of Co, in Swarna estuary wherein it posed a high risk of
      toxicity to organisms associated with the sediments.

PMID- 26210610
TI  - Transcriptional expression levels and biochemical markers of oxidative stress in
      the earthworm Eisenia andrei after exposure to 2,4-dichlorophenoxyacetic acid
      (2,4-D).
AB  - This study investigated the stress response of earthworms (Eisenia andrei) to
      exposure to a commonly used herbicide, 2,4 dichloro-phenoxy-acetic acid (2,4-D).
      We evaluated both stress biomarkers and the transcriptional expression levels and
      activity of three enzymes involved in oxidative stress responses. Earthworms were
      exposed to three sublethal concentration of 2,4-D (3.5, 7, and 14 mg kg(-1)) for
      7 and 14 days. Exposure to 7 and 14 mg kg(-1) 2,4-D significantly reduced both
      worm body weight and lysosomal membrane stability (LMS); the latter is a
      sensitive stress biomarker in coelomocytes. Exposure to 2,4-D caused a pronounced
      increase in the accumulation of malonedialdehyde (MDA), a marker of oxidative
      stress, and significantly increased the activity of the antioxidant enzymes
      catalase (CAT), superoxide dismutase (SOD),and glutathione-S-transferase (GST).
      Compared to expression in controls, the expression levels of the sod, cat, and
      gst genes increased in worms exposed to all three 2,4-D doses for 7 days.
      However, after 14 days of exposure, only the expression of the gst gene remained
      higher than controls. These data provide new insights into the cytotoxicity of
      2,4-D in the earthworm E. andrei and should be carefully considered in view of
      the biological effects of herbicides in soils organisms.

PMID- 26210611
TI  - Imputation approaches for potential outcomes in causal inference.
AB  - BACKGROUND: The fundamental problem of causal inference is one of missing data,
      and specifically of missing potential outcomes: if potential outcomes were fully
      observed, then causal inference could be made trivially. Though often not
      discussed explicitly in the epidemiological literature, the connections between
      causal inference and missing data can provide additional intuition. METHODS: We
      demonstrate how we can approach causal inference in ways similar to how we
      address all problems of missing data, using multiple imputation and the
      parametric g-formula. RESULTS: We explain and demonstrate the use of these
      methods in example data, and discuss implications for more traditional approaches
      to causal inference. CONCLUSIONS: Though there are advantages and disadvantages
      to both multiple imputation and g-formula approaches, epidemiologists can benefit
      from thinking about their causal inference problems as problems of missing data,
      as such perspectives may lend new and clarifying insights to their analyses.

PMID- 26210612
TI  - Effects of the X:IT smoking intervention: a school-based cluster randomized
      trial.
AB  - BACKGROUND: Uptake of smoking in adolescence is still of major public health
      concern. Evaluations of school-based programmes for smoking prevention show mixed
      results. The aim of this study was to examine the effect of X:IT, a multi
      component school-based programme to prevent adolescent smoking. METHODS: Data
      from a Danish cluster randomized trial included 4041 year-7 students (mean age:
      12.5) from 51 intervention and 43 control schools. Outcome measure 'current
      smoking' was dichotomized into smoking daily, weekly, monthly or more seldom vs
      do not smoke. Analyses were adjusted for baseline covariates: sex, family
      socioeconomic position (SEP), best friend's smoking and parental smoking. We
      performed multilevel, logistic regression analyses of available cases and
      intention-to-treat (ITT) analyses, replacing missing outcome values by multiple
      imputation. RESULTS: At baseline, 4.7% and 6.8% of the students at the
      intervention and the control schools smoked, respectively. After 1 year of the
      intervention, the prevalence was 7.9% and 10.7%, respectively. At follow-up, 553
      students (13.7%) did not answer the question on smoking. Available case analyses:
      crude odds ratios (OR) for smoking at intervention schools compared with control
      schools: 0.65 (0.48-0.88) and adjusted: 0.70 (0.47-1.04). ITT analyses: crude OR
      for smoking at intervention schools compared with control schools: 0.67 (0.50
      0.89) and adjusted: 0.61 (0.45-0.82). CONCLUSIONS: Students at intervention
      schools had a lower risk of smoking after a year of intervention in year 7. This
      multi-component intervention involving educational, parental and context-related
      intervention components seems to be efficient in lowering or postponing smoking
      uptake in Danish adolescents.

PMID- 26210613
TI  - Cohort Profile: The Copenhagen Aging and Midlife Biobank (CAMB).

PMID- 26210614
TI  - [Space medicine: Origins and current status in Mexico].

PMID- 26210615
TI  - Alpha-fetoprotein (AFP) modulates the effect of serum albumin on brain
      development by restraining the neurotrophic effect of oleic acid.
AB  - We have previously shown that serum albumin controls perinatal rat brain
      development through the regulation of oleic acid synthesis by astrocytes. In
      fact, oleic acid synthesized and released by astrocytes promoted neurite growth,
      neuron migration and the arrangement of prospective synapses. In this work we
      show that alpha-fetoprotein (AFP) is also present in the brain during embryonic
      development, its concentrations peaking at E15.5 and at E19.5. However, after
      E19.5 AFP concentrations plummeted concurrently with a sharp increase in serum
      albumin concentrations. At E15.5, AFP is present in caudal regions of the brain,
      particularly in brain areas undergoing differentiation during this period, such
      as the thalamic reticular nucleus of the thalamus, the hypothalamus, the amygdala
      and the hippocampus. Albumin was not detected in the brain at E15.5 but stained
      brain cells substantially on day E19.5, showing a very similar distribution to
      that of AFP under the same circumstances. The concentrations of free oleic acid
      in the brain were inversely correlated with those of AFP, suggesting that the
      signals elicited by AFP and oleic acid can be inversely associated. GAP-43, a
      marker of axonal growth that is highly expressed by the presence of oleic acid,
      was not co-localized with AFP except in the marginal zone and areas delimiting
      the subplate. AFP prevented the increase in GAP-43 expression caused by the
      presence of oleic acid in neurons in primary culture in vitro and in organotypic
      cultures of embryonic rat brain ex vivo, suggesting that AFP may modulate the
      effect of serum albumin on brain development. 

PMID- 26210616
TI  - Preserved dichotomy but highly irregular and burst discharge in the basal ganglia
      in alert dystonic rats at rest.
AB  - Despite its prevalence, the underlying pathophysiology of dystonia remains poorly
      understood. Using our novel tri-component classification algorithm, extracellular
      neuronal activity in the globus pallidus (GP), STN, and the entopeduncular
      nucleus (EP) was characterized in 34 normal and 25 jaundiced dystonic Gunn rats
      with their heads restrained while at rest. In normal rats, neurons in each
      nucleus were similarly characterized by two physiologically distinct types:
      regular tonic with moderate discharge frequencies (mean rates in GP, STN and EP
      ranging from 35-41 spikes/s) or irregular at slower frequencies (17-20 spikes/s),
      with a paucity of burst activity. In dystonic rats, these nuclei were also
      characterized by two distinct principal neuronal patterns. However, in marked
      difference, in the dystonic rats, neurons were primarily slow and highly
      irregular (12-15 spikes/s) or burst predominant (14-17 spikes/s), with maintained
      modest differences between nuclei. In GP and EP, with increasing severity of
      dystonia, burstiness was moderately further increased, irregularity mildly
      further increased, and discharge rates mildly further reduced. In contrast, these
      features did not appreciably change in STN with worsening dystonia. Findings of a
      lack of bursting in GP, STN and EP in normal rats in an alert resting state and
      prominent bursting in dystonic Gunn rats suggest that cortical or other external
      drive is normally required for bursting in these nuclei and that spontaneous
      bursting, as seen in dystonia and Parkinson's disease, is reflective of an
      underlying pathophysiological state. Moreover, the extent of burstiness appears
      to most closely correlate with the severity of the dystonia.

PMID- 26210617
TI  - Astaxanthin reduces matrix metalloproteinase-9 expression and activity in the
      brain after experimental subarachnoid hemorrhage in rats.
AB  - We have previously shown that astaxanthin (ATX) reduces the blood-brain barrier
      (BBB) disruption and neurovascular dysfunction following subarachnoid hemorrhage
      (SAH) insults. However, the underlying mechanisms remain unclear. It is known
      that the matrix metalloproteinases (MMPs), especially matrix metalloproteinase-9
      (MMP-9) plays a crucial role in the pathogenesis of secondary brain injury after
      SAH. And ATX has the ability to regulate MMP-9 in other models. Herein, we
      investigated whether ATX could ameliorate MMP-9 activation and expression in a
      rat model of SAH. A total of 144 rats were randomly divided into the following
      groups: control group (n=36), SAH group (n=36), SAH+vehicle group (n=36), and
      SAH+ATX group (n=36). The SAH model was induced by injection of 0.3 ml autologous
      blood into the prechiasmatic cistern. ATX (20 MUl of 0.1 mmol) or vehicle was
      administered intracerebroventricularly 30 min after SAH induction. Mortality,
      neurological function, brain edema and blood-brain barrier (BBB) permeability
      were measured at 24 and 72 h after SAH. Biochemical and zymographic methods were
      used to analyze MMP-9 expression and activity in brain samples.
      Immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL) staining were also evaluated at 24h. Our data indicated that
      ATX could significantly reduce the expression and activity of MMP-9, leading to
      the amelioration of brain edema, BBB impairment, neurological deficits and TUNEL
      positive cells at 24h but not 72 h after SAH. The ATX-mediated down-regulation of
      MMP-9 was correlated with the decreased levels of IL-1beta, TNF-alpha, oxidative
      stress, activated microglia and infiltrating neutrophils. These results suggest
      that the neurovascular protection of ATX in SAH is partly associated with the
      inhibition of MMP-9 expression and activity.

PMID- 26210618
TI  - Neuroprotective effects of 3-O-demethylswertipunicoside against MPTP-induced
      Parkinson's disease in vivo and its antioxidant properties in vitro.
AB  - 3-O-demethylswertipunicoside (3-ODS) has been reported to protect dopaminergic
      neurons against neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP(+)) in
      PC12 cells. Here, we investigate the neuroprotective effects in vivo and
      antioxidant activities in vitro of 3-ODS. In the 1-methyl-4-phenyl-1,2,3,6-
      tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD), 3-ODS
      dose-dependently improved motor coordination (as shown by rotarod test),
      increased the contents of dopamine (DA) and its metabolites in the striatum, and
      increased the number of tyrosine hydroxylase (TH)-positive neurons in the
      substantia nigra (SN). In addition, 3-ODS also increased the spine density in
      hippocampal CA1 neurons. In antioxidant assays, 3-ODS showed a strong capacity in
      scavenging hydroxyl radical, superoxide anion and 1, 1-diphenyl-2-picrylhydrazyl
      (DPPH) radical in a concentration-dependent manner. Taken together, we conclude
      that 3-ODS attenuates the PD-related motor deficits mainly through its
      neuroprotective effects, growth-promoting effects on spine density, and its
      antioxidant activities.

PMID- 26210619
TI  - Childhood Obesity: Causes, Consequences, and Management.
AB  - One-third of North American children are overweight or obese. Pathologic obesity
      accounts for only a small percentage of these cases. The vast majority are the
      result of a complex interaction of genetic and hormonal, nutritional, physical
      activity, and physical and social environmental factors. Obesity increases the
      risk for various cardiometabolic, pulmonary, and psychosocial complications for
      children, which often continues into adulthood. Multidisciplinary care, focusing
      on family-centered behavior change, is an evidence-based, essential part of the
      treatment, along with pharmacologic and surgical options for more complex cases.
      Prevention and early intervention strategies are key to reversing the obesity
      epidemic. 

PMID- 26210620
TI  - The Child with Multiple Fractures, What Next?
AB  - Fractures are common during childhood; however, they can also be the presenting
      symptom of primary or secondary causes of bone fragility. The challenge is to
      identify those children who warrant further investigation. In children who
      present with multiple fractures that are not commonly associated with mild to
      moderate trauma or whose fracture count is greater than what is typically seen
      for their age, an initial evaluation, including history, physical examination,
      biochemistry, and spinal radiography, should be performed. In children with bone
      pain or evidence of more significant bone fragility, referral for specialist
      evaluation and consideration of pharmacologic treatment may be warranted. 

PMID- 26210621
TI  - Preventing Diabetic Ketoacidosis.
AB  - Diabetic ketoacidosis (DKA) is a major cause of morbidity and mortality in
      children with type 1 diabetes mellitus (T1DM). This article examines the factors
      associated with DKA in children with T1DM, both at first presentation and in
      recurrent cases. The challenge for future research is to find effective ways to
      improve primary care physician and general community awareness of T1DM to reduce
      DKA at presentation and develop practical, cost-effective programs to reduce
      recurrent DKA. 

PMID- 26210622
TI  - The Impact of Technology on Current Diabetes Management.
AB  - Technological innovations have revolutionized the treatment of type 1 diabetes.
      Although technological advances can potentially improve diabetes outcomes,
      maintenance of target glycemic control, at the present time, remains largely
      dependent on patient and family motivation, competence, and adherence to daily
      diabetes care requirements. Trials of closed loop or "artificial pancreas"
      technology show great promise to automate insulin delivery and achieve near
      normal glucose control and reduced hypoglycemia with minimal patient
      intervention. 

PMID- 26210624
TI  - The Impact of Diabetes on Brain Function in Childhood and Adolescence.
AB  - A constant supply of glucose to the brain is critical for normal cerebral
      metabolism. The dysglycemia of type 1 diabetes (T1D) can affect activity,
      survival, and function of neural cells. Clinical studies in T1D have shown
      impairments in brain morphology and function. The most neurotoxic milieu seems to
      be young age and/or diabetic ketoacidosis at onset, severe hypoglycemia under the
      age of 6 years followed by chronic hyperglycemia. Adverse cognitive outcomes seem
      to be associated with poorer mental health outcomes. It is imperative to improve
      outcomes by investigating the mechanisms of injury so that neuroprotective
      strategies independent of glycemia can be identified. 

PMID- 26210625
TI  - Interpreting Minor Variations in Thyroid Function or Echostructure: Treating
      Patients, Not Numbers or Images.
AB  - Overt thyroid dysfunction is documented by serum thyrotropin or T4 concentrations
      are often ordered for nonspecific complaints and will by definition fall outside
      of the 95% reference range 5% of the time. In addition, most laboratories quote
      adult ranges, which are not necessarily applicable to young children, and
      regression toward the mean is common, justifying that the test be repeated before
      embarking on treatment. On the other hand, neck ultrasounds are frequently
      performed for diffuse goiter or non-thyroid conditions. Yet, an ultrasound is not
      required to make a diagnosis of Hashimoto thyroiditis and small cysts and nodules
      discovered incidentally often lead to unjustified concerns about neoplasia. 

PMID- 26210626
TI  - Disorders of Menstruation in Adolescent Girls.
AB  - Abnormal menstruation in adolescent girls can cause psychological and physical
      strain from excess, unpredictable, painful, or even absent bleeding. Care
      providers who understand what is normal and what is concerning can educate and
      often reassure the young woman and her family. When there is an abnormal or
      concerning scenario, they can initiate investigations and/or treatment in an
      expedient fashion to limit psychosocial and/or physical morbidity. This article
      provides pediatricians, family doctors, nurse practitioners, and adult
      gynecologists with the knowledge and understanding of the common complaints,
      differential diagnoses, and treatment strategies. 

PMID- 26210623
TI  - Long-term Outcomes in Youths with Diabetes Mellitus.
AB  - In this article, the author reviews the long-term outcomes and their precursors
      of type 1 diabetes starting in youth. The author also contrasts the changing
      incidence of these long-term complications as we have moved from the pre-Diabetes
      Control and Complications Trial (DCCT) to the post-DCCT standard of care and
      reviews the emerging data related to complications in youths with type 2
      diabetes. Finally, the author reviews the recent understanding related to the
      effects of diabetes on the brain and cognition. 

PMID- 26210627
TI  - Short Stature: Is It a Psychosocial Problem and Does Changing Height Matter?
AB  - Some proponents of recombinant human growth hormone (rhGH) treatment in growth
      hormone-sufficient children cite height, as an isolated physical characteristic,
      as being associated with psychosocial morbidity. Others question the reliability
      of the evidence underpinning the quality-of-life rationale for treatment as well
      as the bioethics of rhGH treatment. The following questions are addressed: (1) Is
      short stature an obstacle to positive psychosocial adjustment? and (2) Does
      increasing height with rhGH treatment make a difference to the person's
      psychosocial adaptation and quality of life? Three clinical case examples are
      used to illustrate the complexities associated with decision-making surrounding
      rhGH use. 

PMID- 26210628
TI  - Approach to the Infant with a Suspected Disorder of Sex Development.
AB  - A newborn with genital ambiguity requires careful diagnostic evaluation to
      identify the underlying etiology in an efficient manner and assign gender without
      lengthy delay. The infant's family needs comprehensive psychosocial support. Such
      infants should be referred to a multidisciplinary team with expertise in
      disorders of sex development. 

PMID- 26210629
TI  - Gender Variance and Dysphoria in Children and Adolescents.
AB  - Gender variant and transgender youth are seeking medical care at younger ages.
      Pediatricians and other primary care physicians are often the first professionals
      who encounter such youth and their families. The goals of this article are to
      provide information on the epidemiology and natural history of gender variant and
      transgender youth, current clinical practice guidelines regarding the use of
      puberty blockers and cross-sex hormones for transgender youth, and limitations
      and challenges to optimal care. 

PMID- 26210630
TI  - Hyperinsulinemic Hypoglycemia.
AB  - In hyperinsulinemic hypoglycemia (HH) there is dysregulation of insulin secretion
      from pancreatic beta-cells. Insulin secretion becomes inappropriate for the level
      of blood glucose leading to severe hypoglycemia. HH is associated with a high
      risk of brain injury because insulin inhibits lipolysis and ketogenesis thus
      preventing the generation of alternative brain substrates (such as ketone
      bodies). Hence HH must be diagnosed as soon as possible and the management
      instituted appropriately to prevent brain damage. This article reviews the
      mechanisms of glucose physiology in the newborn, the mechanisms of insulin
      secretion, the etiologic types of HH, and its management. 

PMID- 26210631
TI  - Genome, Exome, and Targeted Next-Generation Sequencing in Neonatal Diabetes.
AB  - The use of targeted gene panels now allows the analysis of all the genes known to
      cause a disease in a single test. For neonatal diabetes, this has resulted in a
      paradigm shift with patients receiving a genetic diagnosis early and the genetic
      results guiding their clinical management. Exome and genome sequencing are
      powerful tools to identify novel genetic causes of known diseases. For neonatal
      diabetes, the use of these technologies has resulted in the identification of 2
      novel disease genes (GATA6 and STAT3) and a novel regulatory element of PTF1A, in
      which mutations cause pancreatic agenesis. 

PMID- 26210632
TI  - Pediatric Endocrinology and Diabetes.

PMID- 26210633
TI  - Pediatric Diabetes and Endocrinology.

PMID- 26210634
TI  - T (brachyury) is linked to a Mendelian form of neural tube defects in humans.

PMID- 26210635
TI  - Erratum to: Sexual dimorphism in cranial morphology among modern South Africans.

PMID- 26210636
TI  - A potential new metabolite of gamma-hydroxybutyrate: sulfonated gamma
      hydroxybutyric acid.
AB  - Detection of gamma-hydroxybutyric acid (GHB) became crucial in many clinical and
      forensic settings due to its increasing use for recreational purposes and drug
      facilitated sexual assault. Its narrow window of detection of about 3-12 h in
      urine represents a major problem. Analogous to ethyl glucuronide, the recently
      identified GHB-glucuronide exhibits a longer window of detection than the parent
      drug. It appeared reasonable that a sulfonated metabolite of GHB (GHB-SUL) will
      also be formed. Due to the lack of an appropriate standard, GHB was incubated
      with a human liver cytosolic fraction to produce GHB-SUL. Following development
      of a liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay to measure
      GHB and GHB-SUL, authentic urine samples (n = 5) were tested for GHB-SUL. These
      investigations revealed detectable signals of both GHB and GHB-SUL, strongly
      indicating that GHB is not only glucuronidated but also sulfonated. Given that
      sulfonated metabolites generally have longer half-life times than the
      corresponding free drugs, GHB-SUL may serve as a biomarker of GHB misuse along
      with its glucuronide.

PMID- 26210637
TI  - Reduced cellular DNA repair capacity after environmentally relevant arsenic
      exposure. Influence of Ogg1 deficiency.
AB  - Inorganic arsenic (i-As) is a genotoxic and carcinogenic environmental
      contaminant known to affect millions of people worldwide. Our previous work
      demonstrated that chronic sub-toxic i-As concentrations were able to induce
      biologically significant levels of genotoxic and oxidative DNA damage that were
      strongly influenced by the Ogg1 genotype. In order to study the nature of the
      observed levels of damage and the observed differences between MEF Ogg1(+/+) and
      Ogg1(-/-) genetic backgrounds, the genotoxic and oxidative DNA repair kinetics of
      18-weeks exposed MEF cells were evaluated by the comet assay. Results indicate
      that MEF Ogg1(+/+) and Ogg1(-/-) cells chronically exposed to i-As repair the DNA
      damage induced by arsenite, potassium bromide and UVC radiation less efficiently
      than control cells, being that observation clearly more pronounced in MEF Ogg1(-/
      ) cells. Consequently, exposed cells accumulate a higher percentage of unrepaired
      DNA damage at the end of the repair period. As an attempt to eliminate i-As
      associated toxicity, chronically exposed MEF Ogg1(-/-) cells overexpress the
      arsenic metabolizing enzyme As3mt. This adaptive response confers cells a
      significant resistance to i-As-induced cell death, but at expenses of
      accumulating high levels of DNA damage due to their repair impairment. Overall,
      the work presented here evidences that i-As chronic exposure disrupts the normal
      cellular repair function, and that oxidative DNA damage-and Ogg1 deficiency
      exacerbates this phenomenon. The observed cell death resistance under a chronic
      scenario of genotoxic and oxidative stress may in turn contribute to the
      carcinogenic effects of i-As. 

PMID- 26210638
TI  - Continuous composite finite-time convergent guidance laws with autopilot dynamics
      compensation.
AB  - This paper has proposed two continuous composite finite-time convergent guidance
      laws to intercept maneuvering targets in the presence of autopilot lag: one is
      for hit-to-kill and the other is for zeroing the line-of-sight (LOS) angular
      rate. More specifically, the nonlinear disturbance observer (NDOB) is used to
      estimate the lumped uncertainty online while the finite-time control technique is
      used to fulfill the design goal in finite time. The key feature in derivation of
      the proposed guidance law is that two integral-type Lyapunov functions are used
      to avoid analytic differentiation of virtual control law encountered with
      traditional backstepping. The finite-time stability of the closed-loop nonlinear
      observer-controller system is established using finite-time bounded (FTB)
      function and Lyapunov function methods. Numerical simulations with some
      comparisons are carried out to demonstrate the superiority of the proposed
      method. 

PMID- 26210640
TI  - Insidious: Takayasu Arteritis.

PMID- 26210639
TI  - De novo assembly and characterization of global transcriptome of coconut palm
      (Cocos nucifera L.) embryogenic calli using Illumina paired-end sequencing.
AB  - Production and supply of quality planting material is significant to coconut
      cultivation but is one of the major constraints in coconut productivity. Rapid
      multiplication of coconut through in vitro techniques, therefore, is of paramount
      importance. Although somatic embryogenesis in coconut is a promising technique
      that will allow for the mass production of high quality palms, coconut is highly
      recalcitrant to in vitro culture. In order to overcome the bottlenecks in coconut
      somatic embryogenesis and to develop a repeatable protocol, it is imperative to
      understand, identify, and characterize molecular events involved in coconut
      somatic embryogenesis pathway. Transcriptome analysis (RNA-Seq) of coconut
      embryogenic calli, derived from plumular explants of West Coast Tall cultivar,
      was undertaken on an Illumina HiSeq 2000 platform. After de novo transcriptome
      assembly and functional annotation, we have obtained 40,367 transcripts which
      showed significant BLASTx matches with similarity greater than 40 % and E value
      of <=10(-5). Fourteen genes known to be involved in somatic embryogenesis were
      identified. Quantitative real-time PCR (qRT-PCR) analyses of these 14 genes were
      carried in six developmental stages. The result showed that CLV was upregulated
      in the initial stage of callogenesis. Transcripts GLP, GST, PKL, WUS, and WRKY
      were expressed more in somatic embryo stage. The expression of SERK, MAPK, AP2,
      SAUR, ECP, AGP, LEA, and ANT were higher in the embryogenic callus stage compared
      to initial culture and somatic embryo stages. This study provides the first
      insights into the gene expression patterns during somatic embryogenesis in
      coconut.

PMID- 26210641
TI  - Identical Twins, Matching Symptoms: Hypersensitivity Pneumonitis.

PMID- 26210643
TI  - A sense of excitement for a specific Lp(a)-lowering therapy.

PMID- 26210642
TI  - Antisense therapy targeting apolipoprotein(a): a randomised, double-blind,
      placebo-controlled phase 1 study.
AB  - BACKGROUND: Lipoprotein(a) (Lp[a]) is a risk factor for cardiovascular disease
      and calcific aortic valve stenosis. No effective therapies to lower plasma Lp(a)
      concentrations exist. We have assessed the safety, pharmacokinetics, and
      pharmacodynamics of ISIS-APO(a)Rx, a second-generation antisense drug designed to
      reduce the synthesis of apolipoprotein(a) (apo[a]) in the liver. METHODS: In this
      randomised, double-blind, placebo-controlled, phase 1 study at the PAREXEL
      Clinical Pharmacology Research Unit (Harrow, Middlesex, UK), we screened for
      healthy adults aged 18-65 years, with a body-mass index less than 32.0 kg/m(2),
      and Lp(a) concentration of 25 nmol/L (100 mg/L) or more. Via a randomisation
      technique, we randomly assigned participants to receive a single subcutaneous
      injection of ISIS-APO(a)Rx (50 mg, 100 mg, 200 mg, or 400 mg) or placebo (3:1) in
      the single-dose part of the study or to receive six subcutaneous injections of
      ISIS-APO(a)Rx (100 mg, 200 mg, or 300 mg, for a total dose exposure of 600 mg,
      1200 mg, or 1800 mg) or placebo (4:1) during a 4 week period in the multi-dose
      part of the study. Participants, investigators, and study staff were masked to
      the treatment assignment, except for the pharmacist who prepared the ISIS
      APO(a)Rx or placebo. The primary efficacy endpoint was the percentage change from
      baseline in Lp(a) concentration at 30 days in the single-dose cohorts and at 36
      days for the multi-dose cohorts. Safety and tolerability was assessed 1 week
      after last dose and included determination of the incidence, severity, and dose
      relation of adverse events and changes in laboratory variables, including lipid
      panel, routine haematology, blood chemistry, urinalysis, coagulation, and
      complement variables. Other assessments included vital signs, a physical
      examination, and 12-lead electrocardiograph. This trial is registered with
      European Clinical Trials Database, number 2012-004909-27. FINDINGS: Between Feb
      27, 2013, and July 15, 2013, 47 (23%) of 206 screened volunteers were randomly
      assigned to receive ISIS-APO(a)Rx as a single-dose or multi-dose of ascending
      concentrations or placebo. In the single-dose study, we assigned three
      participants to receive 50 mg ISIS-APO(a)Rx, three participants to receive 100 mg
      ISIS-APO(a)Rx, three participants to receive 200 mg ISIS-APO(a)Rx, three
      participants to receive 400 mg ISIS-APO(a)Rx, and four participants to receive
      placebo. All 16 participants completed treatment and follow-up and were included
      in the pharmacodynamics, pharmacokinetics, and safety analyses. For the multi
      dose study, we assigned eight participants to receive six doses of 100 mg ISIS
      APO(a)Rx, nine participants to receive six doses of 200 mg ISIS-APO(a)Rx, eight
      participants to receive six doses of 300 mg ISIS-APO(a)Rx, and six participants
      to receive six doses of placebo. Whereas single doses of ISIS-APO(a)Rx (50-400
      mg) did not decrease Lp(a) concentrations at day 30, six doses of ISIS-APO(a)Rx
      (100-300 mg) resulted in dose-dependent, mean percentage decreases in plasma
      Lp(a) concentration of 39.6% from baseline in the 100 mg group (p=0.005), 59.0%
      in the 200 mg group (p=0.001), and 77.8% in the 300 mg group (p=0.001). Similar
      reductions were observed in the amount of oxidized phospholipids associated with
      apolipoprotein B-100 and apolipoprotein(a). Mild injection site reactions were
      the most common adverse events. INTERPRETATION: ISIS-APO(a)Rx results in potent,
      dose-dependent, selective reductions of plasma Lp(a). The safety and tolerability
      support continued clinical development of ISIS-APO(a)Rx as a potential
      therapeutic drug to reduce the risk of cardiovascular disease and calcific aortic
      valve stenosis in patients with elevated Lp(a) concentration. FUNDING: Isis
      Pharmaceuticals.

PMID- 26210644
TI  - Gesture as a window onto children's number knowledge.
AB  - Before learning the cardinal principle (knowing that the last word reached when
      counting a set represents the size of the whole set), children do not use number
      words accurately to label most set sizes. However, it remains unclear whether
      this difficulty reflects a general inability to conceptualize and communicate
      about number, or a specific problem with number words. We hypothesized that
      children's gestures might reflect knowledge of number concepts that they cannot
      yet express in speech, particularly for numbers they do not use accurately in
      speech (numbers above their knower-level). Number gestures are iconic in the
      sense that they are item-based (i.e., each finger maps onto one item in a set)
      and therefore may be easier to map onto sets of objects than number words, whose
      forms do not map transparently onto the number of items in a set and, in this
      sense, are arbitrary. In addition, learners in transition with respect to a
      concept often produce gestures that convey different information than the
      accompanying speech. We examined the number words and gestures 3- to 5-year-olds
      used to label small set sizes exactly (1-4) and larger set sizes approximately (5
      10). Children who had not yet learned the cardinal principle were more than twice
      as accurate when labeling sets of 2 and 3 items with gestures than with words,
      particularly if the values were above their knower-level. They were also better
      at approximating set sizes 5-10 with gestures than with words. Further, gesture
      was more accurate when it differed from the accompanying speech (i.e., a gesture
      speech mismatch). These results show that children convey numerical information
      in gesture that they cannot yet convey in speech, and raise the possibility that
      number gestures play a functional role in children's development of number
      concepts. 

PMID- 26210645
TI  - Regulatory roles of Alu transcript on gene expression.
AB  - Alu element is the most successful transposon and it maintains a high level of
      content in primate genome. However, despite the fact that the expression level of
      independent Alu element is rather low under common condition, an increasing
      number of the observations for the Alu transcripts in cells and tissues have been
      reported recently. Alu transcripts play key roles in the network of gene
      expression regulation. The main functions of Alu transcript focus on gene
      regulation both at transcriptional and post-transcriptional levels. This review
      summarizes major functions of Alu transcripts on gene expression and highlights
      molecular mechanisms dependent on conserved sequence or secondary structure in
      order to unravel a relative ubiquitous way that Alu transcript uses to affect the
      whole genome. 

PMID- 26210646
TI  - Elastic hydrogel substrate supports robust expansion of murine myoblasts and
      enhances their engraftment.
AB  - The application of satellite cell-derived myoblasts in regenerative medicine has
      been restricted by the rapid loss of stemness during in vitro cell expansion
      using traditional culture systems. However, studies published in the past decade
      have highlighted the influence of substrate elasticity on stem cell fate and
      revealed that culture on a soft hydrogel substrate can promote self-renewal and
      prolong the regenerative potential of muscle stem cells. Whether hydrogel
      substrates have similar effects after long-term robust expansion remains to be
      determined. Herein we prepared an elastic chitosan/beta-glycerophosphate/collagen
      hydrogel mimicking the soft microenvironment of muscle tissues for use as the
      substrate for satellite cell culture and investigated its influence on long-term
      cell expansion. After 20 passages in culture, satellite cell-derived myoblasts
      cultured on our hydrogel substrate exhibited significant improvements in
      proliferation capability, cell viability, colony forming frequency, and potential
      for myogenic differentiation compared to those cultured on a routine rigid
      culture surface. Immunochemical staining and western blot analysis both confirmed
      that myoblasts cultured on the hydrogel substrate expressed higher levels of
      several differentiation-related markers, including Pax7, Pax3, and SSEA-1, and a
      lower level of MyoD compared to myoblasts cultured on rigid culture plates (all
      p<0.05). After transplantation into the tibialis anterior of nude mice, myoblasts
      that had been cultured on the hydrogel substrate demonstrated a significantly
      greater engraftment efficacy than those cultured on the traditional surface.
      Collectively, these results indicate that the elastic hydrogel substrate
      supported robust expansion of murine myoblasts and enhanced their engraftment in
      vivo.

PMID- 26210647
TI  - Facial, vocal and musical emotion recognition is altered in paranoid
      schizophrenic patients.
AB  - Disturbed processing of emotional faces and voices is typically observed in
      schizophrenia. This deficit leads to impaired social cognition and interactions.
      In this study, we investigated whether impaired processing of emotions also
      affects musical stimuli, which are widely present in daily life and known for
      their emotional impact. Thirty schizophrenic patients and 30 matched healthy
      controls evaluated the emotional content of musical, vocal and facial stimuli.
      Schizophrenic patients are less accurate than healthy controls in recognizing
      emotion in music, voices and faces. Our results confirm impaired recognition of
      emotion in voice and face stimuli in schizophrenic patients and extend this
      observation to the recognition of emotion in musical stimuli. 

PMID- 26210648
TI  - Darth Vulcan? In support of Anakin Skywalker suffering from borderline
      personality disorder.

PMID- 26210649
TI  - Does military sexual trauma moderate the impact of critical warzone experiences?
AB  - The present research sought to replicate the finding that military sexual trauma
      (MST) moderates the effect of critical warzone experiences on mental health
      outcomes in a sample of male veterans. One-hundred eighty-one male veterans
      completed measures of MST, critical warzone experiences, and mental health
      symptoms. The hypothesized interaction was not significant, nor was a significant
      main effect observed for MST. In contrast, both critical warzone experiences and
      childhood maltreatment had significant main effects. 

PMID- 26210650
TI  - PTSD and obesity in younger and older veterans: Results from the mind your heart
      study.
AB  - Posttraumatic stress disorder (PTSD) is increasingly recognized as a relatively
      common condition that is associated with poor health, including obesity. With a
      sizable proportion of the population approaching older adulthood, it is important
      to understand PTSD-health associations in the context of age. Participants were
      recruited from two Veterans Administration medical centers and included 380
      patients age 60 and over and 365 under age 60. PTSD diagnosis was determined by
      the Clinician Administered PTSD Scale. BMI was trichotomized into normal/under
      (<=24.9), overweight (25.0-29.9), and obese (>=30.0). Models were run in the
      total sample, as well as stratified by age group, and adjusted for demographics,
      depression, antipsychotic medication use, and physical activity. Current PTSD was
      associated with greater likelihood of overweight and obesity in the total sample,
      and lifetime PTSD was associated with significantly increased odds of obesity. In
      the stratified models, current and lifetime PTSD were associated with increased
      likelihood of overweight and obesity in the older group only. Results suggest
      that PTSD is associated with risk for overweight and obesity, an effect that may
      be particularly strong in older adults. These findings support the importance of
      examining PTSD and potential health correlates across the life course. 

PMID- 26210651
TI  - Clinical variables associated with suicide attempts in schizophrenia before and
      after the first episode.
AB  - The aim of this study was to investigate variables associated with suicide
      attempts in schizophrenia before and after the first episode. We evaluated
      history of past sucide attempts, clinical symptoms, level of functioning and
      cognitive performances of 172 patients with first-episode schizophrenia at first
      admission. Information was collected regarding clinical symptom severity,
      treatment compliance, and suicide attempts during the follow-up. We found that
      16.5% of the patients attempted suicide before admission, and 6.2% of them
      attempted suicide during the follow-up. The patients who had attempted suicide
      before admission were mostly women, and more likely to be hospitalized in first
      year of follow up. BPRS-depression subscale score at admission and
      alcohol/substance use appeared as independent variables that found associated
      with suicide attempts prior to admission in logistic regression analysis. The
      patients who attempted suicide during the follow-up had significantly higher BPRS
      depression subcale scores at sixth months of follow-up. Treatment compliance
      during the first 6 months and duration of remission was lower in this group. Our
      findings suggest that longer duration of first hospital treatment, the presence
      of depressive symptoms, and nonadherence to treatment in early phases of follow
      up after FES are predictors of suicide attempts. On the other hand, keeping
      remission during the follow-up protects against suicide attempts. 

PMID- 26210652
TI  - Mental health problems and resilience in international adoptees: Results from a
      population-based study of Norwegian adolescents aged 16-19 years.
AB  - The aim of the study was to investigate mental health and resilience in
      adolescents who have been internationally adopted and their non-adopted peers and
      examine the potential interaction between adoption status and resilience on
      mental health problems. Data from the population based youth@hordaland-survey,
      conducted in Hordaland County, Norway, in 2012 was used. In all, 10 257
      adolescents aged 16-19 years provided self-reported data on several mental health
      instruments. Of these, 45 adolescents were identified as internationally adopted.
      Adoptees reported more symptoms of depression, attention-deficit/hyperactivity
      disorder (ADHD), obsessive compulsive disorder (OCD) and perfectionism than non
      adopted adolescents, but there were no differences regarding resilience.
      Adolescents with higher resilience scores reported fewer symptoms of mental
      health problems, however, no interaction effects were found for adoption status
      and total resilience score on measures of mental health problems. Our findings
      indicate that knowledge of resilience factors can form the basis for preventive
      interventions. 

PMID- 26210653
TI  - The effect of internal mammary lymph node biopsy on the therapeutic decision and
      survival of patients with breast cancer.
AB  - BACKGROUND: The role of internal mammary lymph node biopsy (IMLNB) is still being
      discussed in breast cancer treatment. The aim of this study was to investigate
      the role of IMLNB on adjuvant therapy and survival of patients with breast
      cancer. PATEINTS AND METHODS: The data of 72 patients with clinically negative
      axilla and IMLNB were evaluated. IMLNB was performed either through a small
      separate intercostal incision or from the same incision for tumor resection or
      mastectomy by using both blue dye and radioisotope. Pathological analysis was
      performed on formalin-fixed paraffin-embedded tissues. RESULTS: Ten of the
      patients (14%) were IMLNB-positive. The axillary sentinel lymph node and IMLN
      were negative in most of the patients (52.8%). In one patient (1.4%), the axilla
      was negative but the IMLNB was positive. IMLNB changed the pathologic stage in
      eight patients (11%). Adjuvant internal mammary radiotherapy was added to the
      treatment protocol for 10 patients due to IMLNB positivity and adjuvant
      chemotherapy was added in for only one patient with negative axilla. The factors
      found to be related with IMLN positivity were SLN positivity (p = 0.033),
      mastectomy (p = 0.022), and the number of resected IMLN >=2 (p = 0.040). The
      median follow-up time was 115.5 months (range, 30-162 months). The ten-year
      overall survival (OS) rate was 86%. Systemic metastasis (p = 0.007), SLNB
      positivity (p < 0.001), and IMLNB positivity (p = 0.005) were statistically
      related to overall survival. CONCLUSION: IMLNB positivity in patients with breast
      cancer changed the pathologic stage and adjuvant treatment modalities of patients
      and also adversely affected the overall survival.

PMID- 26210654
TI  - Prognostic evaluation of mucin-5AC expression in intrahepatic cholangiocarcinoma,
      mass-forming type, following hepatectomy.
AB  - AIM: This study aimed to investigate the clinicopathological predictors of
      survival in patients with intrahepatic cholangiocarcinoma, mass-forming type (ICC
      MF), following curative intent hepatectomy. METHODS: Clinical characteristics and
      outcomes were analyzed in a series of 42 patients who underwent curative
      hepatectomy for ICC-MF between February 1987 and December 2012. The relationship
      between immunohistochemical expression profiles of mucin (MUC) core proteins
      (MUC2, MUC5AC, and MUC6) and surgical outcomes was examined. RESULTS: The overall
      median follow-up period was 2.6 years (0.2-17.9). Bile duct reconstruction (p =
      0.017), lymph node metastasis (p = 0.049), maximal mass diameter >=5.0 cm (p =
      0.002), and MUC5AC expression (p = 0.003) were identified as significant adverse
      predictors of overall survival by univariate analysis. Bile duct reconstruction
      (p = 0.048), maximal mass diameter >=5.0 cm (p = 0.002), and MUC5AC expression (p
      = 0.005) were found to be independent predictors of poor prognosis by
      multivariate analysis. Maximal mass diameter >=5.0 cm (p = 0.011) was found to be
      an independent predictor for the tumor recurrence. There was a strong correlation
      between MUC5AC expression and lymph node metastasis (p = 0.021). MUC6 expression
      was more frequent in patients with concurrent MUC5AC expression (p = 0.019).
      CONCLUSIONS: MUC5AC expression was significantly related to long-term prognosis
      and aggressive tumor development, and may be a useful prognostic marker.

PMID- 26210655
TI  - Medical androgen deprivation therapy and increased non-cancer mortality in non
      metastatic prostate cancer patients aged >=66 years.
AB  - PURPOSE: To examine the potential relationship between androgen deprivation
      therapy and other-cause mortality (OCM) in patients with prostate cancer treated
      with medical primary-androgen deprivation therapy, prostatectomy, or radiation.
      METHODS: A total of 137,524 patients with non-metastatic PCa treated between 1995
      and 2009 within the Surveillance Epidemiology and End Results Medicare-linked
      database were included. Cox-regression analysis tested the association of ADT
      with OCM. A 40-item comorbidity score was used for adjustment. RESULTS: Overall,
      9.3% of patients harbored stage III-IV disease, and 57.7% of patients received
      ADT. The mean duration of ADT exposure was 22.9 months (median: 9.1; IQR: 2.8
      31.5). Mean and median follow-up were 66.9, and 60.4 months, respectively. At 10
      years, overall-OCM rate was 36.5%; it was 30.6% in patients treated without ADT
      vs. 40.1% in patients treated with ADT (p < 0.001). In multivariable-analysis,
      ADT was associated with an increased risk of OCM (Hazard-ratio [HR]: 1.11, 95%
      Confidence-interval [95% CI]: 1.08-1.13). Patients with no comorbidity (10-year
      OCM excess risk: 9%) were more subject to harm from ADT than patients with high
      comorbidity (10-year OCM excess risk: 4.7%). CONCLUSIONS: In patients with PCa,
      treatment with medical ADT may increase the risk of mortality due to causes other
      than PCa. Whether this is a simple association or a cause-effect relationship is
      unknown and warrants further study in prospective studies.

PMID- 26210656
TI  - Investigating consumers' and informal carers' views and preferences for consumer
      directed care: A discrete choice experiment.
AB  - Consumer directed care (CDC) is currently being embraced internationally as a
      means to promote autonomy and choice for consumers (people aged 65 and over)
      receiving community aged care services (CACSs). CDC involves giving CACS clients
      (consumers and informal carers of consumers) control over how CACSs are
      administered. However, CDC models have largely developed in the absence of
      evidence on clients' views and preferences. We explored CACS clients' preferences
      for a variety of CDC attributes and identified factors that may influence these
      preferences and potentially inform improved design of future CDC models. Study
      participants were clients of CACSs delivered by five Australian providers. Using
      a discrete choice experiment (DCE) approach undertaken in a group setting between
      June and December 2013, we investigated the relative importance to CACS consumers
      and informal (family) carers of gradations relating to six salient features of
      CDC (choice of service provider(s), budget management, saving unused/unspent
      funds, choice of support/care worker(s), support-worker flexibility and level of
      contact with service coordinator). The DCE data were analysed using conditional,
      mixed and generalised logit regression models, accounting for preference and
      scale heterogeneity. Mean ages for 117 study participants were 80 years (87
      consumers) and 74 years (30 informal carers). All participants preferred a CDC
      approach that allowed them to: save unused funds from a CACS package for future
      use; have support workers that were flexible in terms of changing activities
      within their CACS care plan and; choose the support workers that provide their
      day-to-day CACSs. The CDC attributes found to be important to both consumers and
      informal carers receiving CACSs will inform the design of future CDC models of
      service delivery. The DCE approach used in this study has the potential for wide
      applicability and facilitates the assessment of preferences for elements of
      potential future aged care service delivery not yet available in policy. 

PMID- 26210657
TI  - Racial residential segregation and risky sexual behavior among non-Hispanic
      blacks, 2006-2010.
AB  - Sexually transmitted infections (STIs) including human immunodeficiency virus
      (HIV) have disproportionately affected the non-Hispanic black population in the
      United States. A person's community can affect his or her STI risk by the
      community's underlying prevalence of STIs, sexual networks, and social influences
      on individual behaviors. Racial residential segregation-the separation of racial
      groups in a residential context across physical environments-is a community
      factor that has been associated with negative health outcomes. The objective of
      this study was to examine if non-Hispanic blacks living in highly segregated
      areas were more likely to have risky sexual behavior. Demographic and sexual risk
      behavior data from non-Hispanic blacks aged 15-44 years participating in the
      National Survey of Family Growth were linked to Core-Based Statistical Area
      segregation data from the U.S. Census Bureau. Five dimensions measured racial
      residential segregation, each covering a different concept of spatial variation.
      Multilevel logistic regressions were performed to test the effect of each
      dimension on sexual risk behavior controlling for demographics and community
      poverty. Of the 3643 participants, 588 (14.5%) reported risky sexual behavior as
      defined as two or more partners in the last 12 months and no consistent condom
      use. Multilevel analysis results show that racial residential segregation was
      associated with risky sexual behavior with the association being stronger for the
      centralization [aOR (95% CI)][2.07 (2.05-2.08)] and concentration [2.05 (2.03
      2.07)] dimensions. This suggests risky sexual behavior is more strongly
      associated with neighborhoods with high concentrations of non-Hispanic blacks and
      an accumulation of non-Hispanic blacks in an urban core. Findings suggest racial
      residential segregation is associated with risky sexual behavior in non-Hispanic
      blacks 15-44 years of age with magnitudes varying by dimension. Incorporating
      additional contextual factors may lead to the development of interventions that
      promote healthier behaviors and lower rates of HIV and other STIs. 

PMID- 26210658
TI  - Paid maternity leave and childhood vaccination uptake: Longitudinal evidence from
      20 low-and-middle-income countries.
AB  - The availability of maternity leave might remove barriers to improved vaccination
      coverage by increasing the likelihood that parents are available to bring a child
      to the clinic for immunizations. Using information from 20 low-and-middle-income
      countries (LMICs) we estimated the effect of paid maternity leave policies on
      childhood vaccination uptake. We used birth history data collected via
      Demographic and Health Surveys (DHS) to assemble a multilevel panel of 258,769
      live births in 20 countries from 2001 to 2008; these data were merged with
      longitudinal information on the number of full-time equivalent (FTE) weeks of
      paid maternity leave guaranteed by each country. We used Logistic regression
      models that included country and year fixed effects to estimate the impact of
      increases in FTE paid maternity leave policies in the prior year on the receipt
      of the following vaccines: Bacillus Calmette-Guerin (BCG) commonly given at
      birth, diphtheria, tetanus, and pertussis (DTP, 3 doses) commonly given in clinic
      visits and Polio (3 doses) given in clinic visits or as part of campaigns. We
      found that extending the duration of paid maternity leave had a positive effect
      on immunization rates for all three doses of the DTP vaccine; each additional FTE
      week of paid maternity leave increased DTP1, 2 and 3 coverage by 1.38 (95% CI =
      1.18, 1.57), 1.62 (CI = 1.34, 1.91) and 2.17 (CI = 1.76, 2.58) percentage points,
      respectively. Estimates were robust to adjustment for birth characteristics,
      household-level covariates, attendance of skilled health personnel at birth and
      time-varying country-level covariates. We found no evidence for an effect of
      maternity leave on the probability of receiving vaccinations for BCG or Polio
      after adjustment for the above-mentioned covariates. Our findings were consistent
      with the hypothesis that more generous paid leave policies have the potential to
      improve DTP immunization coverage. Further work is needed to understand the
      health effects of paid leave policies in LMICs. 

PMID- 26210659
TI  - Are long-term cancer survivors and physicians discussing health promotion and
      healthy behaviors?
AB  - PURPOSE: This study aimed to (1) describe the proportion of survivors reporting
      that a physician discussed strategies to improve health and (2) identify which
      groups are more likely to report these discussions. METHODS: Lung cancer and
      colorectal cancer (CRC) survivors (>5 years from diagnosis) (n = 874) completed
      questionnaires, including questions on whether, in the previous year, a physician
      discussed (1) strategies to improve health, (2) exercise, and (3) diet habits.
      Chi-square tests and logistic regression models were used to examine whether the
      likelihood of these discussions varied by demographic and clinical
      characteristics. RESULTS: Fifty-nine percent reported that a physician discussed
      strategies to improve health and exercise, 44% reported discussions on diet, and
      24% reported no discussions. Compared to their counterparts, survivors with lower
      education were less likely to report discussing all three areas, but survivors
      with diabetes were more likely. Survivors >= 65 years old were less likely to
      report discussing strategies to improve health and diet. Males and CRC survivors
      reported discussing diet more than their female and lung cancer counterparts,
      respectively. CONCLUSION: The frequency of health promotion discussions varied
      across survivor characteristics. Discussions were more frequently reported by
      some groups, e.g., survivors with diabetes, or among individuals less likely to
      engage in healthy behaviors. In contrast, males and older and less educated
      survivors were less likely to have these discussions. IMPLICATIONS FOR CANCER
      SURVIVORS: Decreasing physician barriers and encouraging patients to discuss
      health promotion, especially in the context of clinical care for older survivors
      and those with low education, is essential for promoting the overall well-being
      of cancer survivors.

PMID- 26210660
TI  - Towards the perfect ARM center: the European Union's criteria for centers of
      expertise and their implementation in the member states. A report from the ARM
      Net.
AB  - BACKGROUND: Pediatric surgeons and patient organisations agree that fewer centers
      for anorectal malformations with larger patient numbers are essential to reach
      better treatment. The European Union transacts a political process which aims to
      realize such centers of expertise for a multitude of rare diseases. All the
      centers on a specific rare disease should constitute an ERN on that disease. ARM
      Net members in different countries report on first experiences with the
      implementation of national directives, identifying opportunities and risks of
      this process. METHODS: Relevant details from the official European legislation
      were analyzed. A survey among the pediatric surgeons of the multidisciplinary ARM
      Net consortium about national implementation was conducted. RESULTS: European
      legislation calls for multidisciplinary centers treating children with rare
      diseases, and proposes a multitude of quality criteria. The member states are
      called to allocate sufficient funding and to execute robust governance and
      oversight, applying clear methods for evaluation. Participation of the patient
      organisations is mandatory. The national implementations all over Europe differ a
      lot in respect of extent and timeframe. CONCLUSIONS: Establishing Centers of
      Expertise and a ERN for anorectal malformations offers great opportunities for
      patient care and research. Pediatric surgeons should be actively engaged in this
      process.

PMID- 26210661
TI  - Formation of Tertiary Interactions during rRNA GTPase Center Folding.
AB  - The 60-nt GTPase center (GAC) of 23S rRNA has a phylogenetically conserved
      secondary structure with two hairpin loops and a 3-way junction. It folds into an
      intricate tertiary structure upon addition of Mg(2+) ions, which is stabilized by
      the L11 protein in cocrystal structures. Here, we monitor the kinetics of its
      tertiary folding and Mg(2+)-dependent intermediate states by observing selected
      nucleobases that contribute specific interactions to the GAC tertiary structure
      in the cocrystals. The fluorescent nucleobase 2-aminopurine replaced three
      individual adenines, two of which make long-range stacking interactions and one
      that also forms hydrogen bonds. Each site reveals a unique response to Mg(2+)
      addition and temperature, reflecting its environmental change from secondary to
      tertiary structure. Stopped-flow fluorescence experiments revealed that kinetics
      of tertiary structure formation upon addition of MgCl2 are also site specific,
      with local conformational changes occurring from 5 ms to 4s and with global
      folding from 1 to 5s. Site-specific substitution with (15)N-nucleobases allowed
      observation of stable hydrogen bond formation by NMR experiments. Equilibrium
      titration experiments indicate that a stable folding intermediate is present at
      stoichiometric concentrations of Mg(2+) and suggest that there are two initial
      sites of Mg(2+) ion association.

PMID- 26210662
TI  - Structure/Function Analysis of Protein-Protein Interactions Developed by the
      Yeast Pih1 Platform Protein and Its Partners in Box C/D snoRNP Assembly.
AB  - In eukaryotes, nucleotide post-transcriptional modifications in RNAs play an
      essential role in cell proliferation by contributing to pre-ribosomal RNA
      processing, ribosome assembly and activity. Box C/D small nucleolar
      ribonucleoparticles catalyze site-specific 2'-O-methylation of riboses, one of
      the most prevalent RNA modifications. They contain one guide RNA and four core
      proteins and their in vivo assembly requires numerous factors including
      (HUMAN/Yeast) BCD1/Bcd1p, NUFIP1/Rsa1p, ZNHIT3/Hit1p, the R2TP complex composed
      of protein PIH1D1/Pih1p and RPAP3/Tah1p that bridges the R2TP complex to the
      HSP90/Hsp82 chaperone and two AAA+ ATPases. We show that Tah1p can stabilize
      Pih1p in the absence of Hsp82 activity during the stationary phase of growth and
      consequently that the Tah1p:Pih1p interaction is sufficient for Pih1p stability.
      This prompted us to establish the solution structure of the Tah1p:Pih1p complex
      by NMR. The C-terminal tail S93-S111 of Tah1p snakes along Pih1p264-344 folded in
      a CS domain to form two intermolecular beta-sheets and one covering loop.
      However, a thorough inspection of the NMR and crystal structures revealed
      structural differences that may be of functional importance. In addition, our NMR
      and isothermal titration calorimetry data revealed the formation of direct
      contacts between Pih1p257-344 and the Hsp82MC domain in the presence of Tah1p. By
      co-expression in Escherichia coli, we demonstrate that Pih1p has two other direct
      partners, the Rsa1p assembly factor and the Nop58p core protein, and in vivo and
      in vitro experiments mapped the required binding domains. Our data suggest that
      these two interactions are mutually exclusive. The implication of this finding
      for box C/D small nucleolar ribonucleoparticle assembly is discussed. 

PMID- 26210664
TI  - Stakeholder perspectives on the new sickness certificate in Victoria: results
      from a mixed-methods qualitative study.
AB  - OBJECTIVE; The aim ofthis study was to present the views of four stakeholder
      groups, namely general practitioners (GP), employers (EMP), injured workers (IW)
      and compensation agents (CA), about the content and usability of the draft of the
      new Victorian sickness certificate. METHODS: A cross-sectional mixed-methods
      qualitative study was conducted in GP clinics and community settings in
      Melbourne, Australia. Interviews were conducted with GPs, EMPs and IWs and one
      focus group discussion was completed with CAs (n = 29). Data were collected
      between October and December 2013. Thematic analysis was performed. RESULTS: All
      stakeholders viewed the new draft certificate as an improvement on the old one.
      GPs saw the certificate as a form of communication, whereas EMPs and CAs saw it
      as a therapeutic device. GPs continued to certify based on incapacity and
      provided little information about what IWs could do on return to work. All groups
      said that assessments for mental health needed more clarity and specificity. GPs,
      EMPs and CAs also said that the new certificates must be electronically available
      and integrated into existing medical software to streamline uptake. CONCLUSIONS:
      To ensure appropriate use of the new certificate, stakeholders must share a
      common understanding about its purpose and the certificate must be incorporated
      into existing medical software. Content on mental health assessment, an area of
      continued difficulty, needs additional refinement. The new certificate replaced
      the old certificate in March 2015; after it has been established in clinical
      practice, an impact evaluation should be completed to determine whether GPs are
      certifying capacity and earlier return to work.

PMID- 26210663
TI  - Epigenetic Modulation of Human Podocyte Vitamin D Receptor in HIV Milieu.
AB  - HIV (human immunodeficiency virus) has been reported to induce podocyte injury
      through down regulation of vitamin D receptor (VDR) and activation of renin
      angiotensin system; however, the involved mechanism is not clear. Since HIV has
      been reported to modulate gene expression via epigenetic phenomena, we asked
      whether epigenetic factors contribute to down regulation of VDR. Kidney cells in
      HIV transgenic mice and HIV-infected podocytes (HIV/HPs) displayed enhanced
      expression of SNAIL, a repressor of VDR. To elucidate the mechanism, we studied
      the effect of HIV on expression of molecules involved in SNAIL repressor complex
      formation and demonstrated that HIV enhances expression of the histone
      deacetylase HDAC1 and DNA methyl transferases DNMT3b and DNMT1. 293T cells, when
      stably transfected with SNAIL (SNAIL/293T), displayed suppressed transcription
      and translation of VDR. In SNAIL/293T cells, co-immunoprecipitation studies
      revealed the association of HDAC1, DNMT3b, DNMT1, and mSin3A with SNAIL.
      Chromatin immunoprecipitation experiments confirmed the presence of the SNAIL
      repressor complex at the VDR promoter. Consistent with the enhanced DNA methyl
      transferase expression in HIV/HPs, there was an increased CpG methylation at the
      VDR promoter. Chromatin immunoprecipitation assay confirmed occurrence of H3K4
      trimethylation on SNAIL promoter. Neither a VDR agonist (VDA) nor an HDAC
      inhibitor (HDACI) nor a demethylating agent (DAC) individually could optimally up
      regulate VDR in HIV milieu. However, VDA and HDACI when combined were successful
      in de-repressing VDR expression. Our findings demonstrate that SNAIL recruits
      multiple chromatin enzymes to form a repressor complex in HIV milieu that down
      regulates VDR expression. 

PMID- 26210666
TI  - Large Bladder Clot-An Unusual Presentation of Neonatal Bilateral Renal Vein
      Thrombosis-Case Report and Review of Literature.
AB  - A 1-day-old boy born at 37 weeks gestation presented with hematuria,
      thrombocytopenia, and palpable irregular right flank mass. Renal ultrasound
      demonstrated large clot within the bladder, bilateral kidney masses with loss of
      corticomedullary differentiation, and reversal of diastolic flow. The patient was
      diagnosed with bilateral renal vein thrombosis and was managed conservatively.
      There was complete resolution of the bladder clot with restoration of
      corticomedullary differentiation bilaterally. We report the first case of renal
      vein thrombosis associated with a large bladder clot in a neonate.

PMID- 26210665
TI  - Environmental hexachlorobenzene exposure and human male reproductive function.
AB  - Hexachlorobenzene (HCB) is a persistent environmental fungicide that may disrupt
      androgen regulation. The aim of this study was to investigate associations
      between HCB levels and biomarkers of male reproductive function. 589 Spouses of
      pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and
      2004. The men provided semen and blood samples and were interviewed. HCB was
      measured in serum by gas chromatography. The mean serum concentrations of HCB
      were higher in Ukraine (182.3ng/g lipid) and Greenland (79.0ng/g lipid) compared
      to Poland (14.2ng/g lipid). Sex hormone binding globulin (SHBG) and free androgen
      index (FAI) were associated with HCB in men from Ukraine and Poland. This study
      spanning large differences in environmental HCB exposure levels shows a positive
      association for SHBG and negative association for FAI with high serum levels of
      HCB in fertile men, but without major consequences for semen quality and the
      Inuit study population. 

PMID- 26210667
TI  - Cardiac Dysrhythmias in Children Undergoing Extracorporeal Shock Wave Lithotripsy
      Under General Anesthesia or Propofol Sedation: A Prospective, Observational
      Cohort Study.
AB  - OBJECTIVE: To assess the frequency and severity of cardiac dysrhythmias and
      identify any intraoperative or postoperative complications in children undergoing
      extracorporeal shock wave lithotripsy (ESWL). METHODS: All children coming to our
      institution for ESWL from June 2014 to January 2015 were prospectively enrolled
      in an observational cohort study. Intraoperative cardiac dysrhythmias and
      perioperative and postoperative complications were recorded. RESULTS: In total,
      21 children aged 1-18 years were enrolled receiving a total of 26 treatments.
      Intravenous sedation was used in 19 cases and general anesthesia with an
      inhalational agent in 7 cases. Cardiac dysrhythmias occurred in 58% of children.
      No hemodynamic instability was noted. No therapies were terminated because of
      dysrhythmias, and there were no postoperative cardiac dysrhythmias. CONCLUSION:
      ESWL remains a safe therapy for children with urinary stone disease. Although we
      experienced more dysrhythmias than currently published literature, there were no
      long-term adverse outcomes and children were able to go home the same day.

PMID- 26210668
TI  - Colon Radiological Delineation Technique Prior to Percutaneous Nephrolithotomy in
      Patients With Horseshoe Kidney.
AB  - OBJECTIVE: To develop a technique that helps avoid colonic injury during
      percutaneous nephrolithotomy (PCNL) in these patients. PATIENTS AND METHODS: PCNL
      was prospectively performed in a cohort of adults with renal stones in a
      horseshoe kidney (HSK). PCNLs were done using a standardized technique in prone
      position in all patients. The colon was radiologically delineated by injecting
      air-through a catheter in the anal canal-to help localize its position in
      relation to the pelvicalyceal system (PCS). Patients were observed in hospital
      for 48 hours postoperatively to detect any potential complications related to the
      PCNL or to the colon insufflation modification. RESULTS: Thirteen adult patients
      (11 men and 2 women) with renal stones in a HSK were included in the study. The
      colon was well radiologically delineated with air in all cases. The PCS was
      successfully accessed, subcostally, with a single access at the upper calyx in 11
      cases and multiple accesses in 2 cases. The colon was in the way of the puncture
      in 2 cases in which we used a more medial access and the colon was successfully
      avoided. Stones were completely removed during the PCNL in 11 of the 13 cases
      (84.6%). One case necessitated intraoperative blood transfusion. No other
      complications were reported by any of the patients who were discharged home after
      48 hours. CONCLUSION: Colonic radiological delineation technique is helpful in
      accessing the PCS quickly, saving the colon, and causing no discomfort to
      patients with renal stones in a HSK.

PMID- 26210669
TI  - Copula based flexible modeling of associations between clustered event times.
AB  - Multivariate survival data are characterized by the presence of correlation
      between event times within the same cluster. First, we build multi-dimensional
      copulas with flexible and possibly symmetric dependence structures for such data.
      In particular, clustered right-censored survival data are modeled using mixtures
      of max-infinitely divisible bivariate copulas. Second, these copulas are fit by a
      likelihood approach where the vast amount of copula derivatives present in the
      likelihood is approximated by finite differences. Third, we formulate conditions
      for clustered right-censored survival data under which an information criterion
      for model selection is either weakly consistent or consistent. Several of the
      familiar selection criteria are included. A set of four-dimensional data on time
      to-mastitis is used to demonstrate the developed methodology.

PMID- 26210670
TI  - Integrated likelihoods in parametric survival models for highly clustered
      censored data.
AB  - In studies that involve censored time-to-event data, stratification is frequently
      encountered due to different reasons, such as stratified sampling or model
      adjustment due to violation of model assumptions. Often, the main interest is not
      in the clustering variables, and the cluster-related parameters are treated as
      nuisance. When inference is about a parameter of interest in presence of many
      nuisance parameters, standard likelihood methods often perform very poorly and
      may lead to severe bias. This problem is particularly evident in models for
      clustered data with cluster-specific nuisance parameters, when the number of
      clusters is relatively high with respect to the within-cluster size. However, it
      is still unclear how the presence of censoring would affect this issue. We
      consider clustered failure time data with independent censoring, and propose
      frequentist inference based on an integrated likelihood. We then apply the
      proposed approach to a stratified Weibull model. Simulation studies show that
      appropriately defined integrated likelihoods provide very accurate inferential
      results in all circumstances, such as for highly clustered data or heavy
      censoring, even in extreme settings where standard likelihood procedures lead to
      strongly misleading results. We show that the proposed method performs generally
      as well as the frailty model, but it is superior when the frailty distribution is
      seriously misspecified. An application, which concerns treatments for a frequent
      disease in late-stage HIV-infected people, illustrates the proposed inferential
      method in Weibull regression models, and compares different inferential
      conclusions from alternative methods.

PMID- 26210671
TI  - Nicotine regulates the expression of UDP-glucuronosyltransferase (UGT) in
      humanized UGT1 mouse brain.
AB  - UDP-glucuronosyltransferase (UGT) is a family of enzymes that catalyze the
      glucuronidation of various compounds, and thereby has an important role in
      metabolism and detoxification of a large number of xenobiotic and endogenous
      compounds. UGTs are present highly in the liver and small intestine, while
      several investigations on quantification of UGT mRNA reported that UGTs were also
      expressed in the brain. However, reported expression patterns of UGT isoforms in
      human brain were often incongruous with each other. In the present study,
      therefore, we investigated UGT mRNA expressions in brains of humanized UGT1
      (hUGT1) mice. We found that among the human UGT1 members, UGT1A1, 1A3, and 1A6
      were expressed in the brain. We further observed that nicotine (3 mg/kg) induced
      the expression of UGT1A3 mRNA in the brain, but not liver. While it was not
      statistically significant, the nicotine treatment resulted in an increase in the
      chenodeoxycholic acid glucuronide-formation activity in the brain microsomes.
      UGT1A3 is involved in metabolism of various antidepressants and non-steroidal
      antiinflammatory drugs, which exhibit their pharmacological effects in the brain.
      Therefore, nicotine-treated hUGT1 mice might be useful to investigate the role of
      brain UGT1A3 in the regulation of local levels of these drugs and their response.

PMID- 26210672
TI  - Effects of 8-methoxypsoralen on the metabolism of 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone in mice.
AB  - 8-Methoxypsoralen (8-MOP) is a well established drug in the treatment of various
      skin diseases. Pretreatment of mice with 8-MOP before administration of 4
      (Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) significantly reduced the
      incidence of NNK-induced tumor. The present study was designed to evaluate the in
      vivo effects of 8-MOP on the bioactivation of NNK in mice. Decrease in the alpha
      hydroxylation of NNK in mouse blood and tissues was observed as the most
      pronounced effect of 8-MOP. The catalytic property of cytochrome P450 2A5
      (CYP2A5) enzyme in mice was determined by the coumarin 7-hydroxylation reaction,
      suggesting that 8-MOP produced remarkable inhibition on CYP2A5 in female C57BL/6
      mice. These results implied that 8-MOP could prevent NNK-induced mutagenesis and
      tumorigenesis in mice through the inhibition of NNK alpha-hydroxylation, which
      may be achieved through the effect of 8-MOP on the bioactivities of CYP2A5. 

PMID- 26210674
TI  - Erratum: Thoracoscopic surgery for bronchobiliary fistula: a case report.

PMID- 26210673
TI  - Value of SPECT-CT Imaging for Middle-Aged Patients with Chronic Anterior Knee
      Pain.
AB  - BACKGROUND: Single-photon emission computed tomography-computed tomography (SPECT
      CT) is a highly sensitive tool for detecting bone metabolism. We determined
      whether subchondral bone metabolism, as indicated by SPECT-CT in the
      patellofemoral (PF) joint, predicts response to conservative management in middle
      aged patients with chronic anterior knee pain (AKP), and whether SPECT-CT results
      correlate with arthroscopic assessments of chondral lesions in the PF joint.
      METHODS: The study group comprised 74 middle-aged patients with chronic AKP. All
      of the patients underwent SPECT-CT, and the results were graded along a scale of
      0 to 3 degrees . After 8 weeks of conservative management, they were grouped as
      responders (n = 40) or non-responders (n = 34) according to symptom improvement.
      We compared the median scintigraphic uptake of the PF joint between the two
      groups, and evaluated the positive predictive value (PPV) of uptake for treatment
      response in each patient. In non-responders, cartilage condition was assessed
      during arthroscopy, and the correlation of scintigraphic uptake with severity of
      the chondral lesion was assessed. RESULTS: The median scintigraphic uptake in the
      patella was higher in non-responders than in responders (2 vs. 1). Among patients
      with higher patella uptake (grade 2 or 3), the PPV for non-response to
      conservative therapy was 62-67 %, whereas it was 24-25 % in patients with lower
      uptake (grade 0 or 1). Patella uptake corresponded strongly with arthroscopic
      assessment of patellar chondral lesions; the correlation was less strong for the
      femoral trochlea. CONCLUSIONS: Increased subchondral bone metabolism in the
      patella is associated with responsiveness to conservative therapy. SPECT-CT can
      benefit clinicians by predicting the treatment response from conservative
      management.

PMID- 26210675
TI  - Reconstruction of organochlorine compound inputs in the Tagus Prodelta.
AB  - Twenty century time-resolved variability of riverine deposits of
      polychlorobiphenyls (PCBs), DDTs, hexachlorocyclohexanes (HCHs) and
      hexachlorobenzene (HCB) was studied in three (210)Pb dated sediment cores
      collected in a depositional shelf area adjacent to the Tagus estuary (the Tagus
      Prodelta). The geographic and temporal distribution patterns were consistent with
      discharge of these organochlorine compounds (OCs) in the area associated with the
      Tagus mouth. Their concentrations were not correlated with the sedimentary total
      organic carbon. The PCB down-core profiles were dominated by CB138 and CB153
      (hexa-CBs) congeners followed by CB180 (hepta-CBs). Principal Component Analysis
      of the congener distributions of these compounds did not define temporal down
      core trends. The ratios of DDT metabolites (p,p'-DDE/p,p'-DDT) were consistent
      with recent DDT inputs into the environment and/or earlier applications and long
      term residence in soils/sediments until these were eroded and remobilized. 

PMID- 26210676
TI  - Peripheral vascular endothelial growth factor as a novel depression biomarker: A
      meta-analysis.
AB  - BACKGROUND: The neurotrophic hypothesis of major depressive disorder (MDD)
      postulates that the pathology of this illness incorporates a down-regulation of
      neurotrophin signaling. Brain-derived neurotrophic factor (BDNF) is the most
      studied neurotrophic mediator regarding the neurobiology of MDD. Nevertheless,
      emerging evidence has implicated the multi-competent angiogenic and neurogenic
      molecule - vascular endothelial growth factor (VEGF) - in hippocampal
      neurogenesis and depression pathophysiology. OBJECTIVE: To compare peripheral
      levels of VEGF between individuals with MDD and healthy controls. METHODS: We
      performed a systematic review and meta-analysis of original studies measuring
      peripheral levels of VEGF in participants with MDD compared to healthy controls.
      We searched the Pubmed/MEDLINE, EMBASE and PsycInfo databases for studies
      published in any language through December 16th, 2014. RESULTS: Fourteen studies
      met eligibility criteria (N=1633). VEGF levels were significantly elevated in
      individuals with MDD when compared to healthy controls (Hedges's g=0.343; 95% CI:
      0.146-0.540; P<0.01). Funnel plot inspection and the Egger's test did not provide
      evidence of publication bias. A significant degree of heterogeneity was observed
      (Q=38.355, df=13, P<0.001; I(2)=66.1%), which was explored through meta
      regression and subgroup analyses. Overall methodological quality, sample for
      assay (plasma versus serum), as well as the matching of MDD and control samples
      for age and gender emerged as significant sources of heterogeneity. CONCLUSIONS:
      Taken together, extant data indicate that VEGF shows promise as a biomarker for
      MDD, and supports that this mediator may be involved in neuroplasticity
      mechanisms underlying the pathophysiology of MDD.

PMID- 26210677
TI  - Comprehensive Assessment of the Impact of Laparoscopic Ovarian Cystectomy on
      Ovarian Reserve.
AB  - STUDY OBJECTIVE: To evaluate the effects of laparoscopic cystectomy of
      endometrioma and nonendometrioma ovarian cyst on ovarian reserve. DESIGN:
      Prospective follow-up study of patients after laparoscopic ovarian cystectomy
      (Canadian Task Force II-2). SETTING: Academic hospital. PATIENTS: Seventy
      patients underwent laparoscopic ovarian cystectomy, with bilateral endometrioma
      (n = 21), unilateral endometrioma (n = 29), and unilateral other benign ovarian
      cyst (n = 20) from February 2011 and May 2012. The control group (n = 20)
      comprised patients treated with laparoscopic myomectomy or laparoscopic
      hydrotubation and fimbrioplasty at the same time period. INTERVENTIONS: All
      laparoscopic operations were applied by suture homeostasis. Ovarian reserve was
      assessed by serum levels of anti-Mullerian hormone (AMH) and follicle-stimulating
      hormone (FSH) and by antral follicle count (AFC), ovarian volume, ovarian stromal
      pulsatility index, and resistance index on the third day of menstruation
      preoperatively and in postoperative months 1.6 and 12. MEASUREMENTS AND MAIN
      RESULTS: FSH levels increased significantly but the AMH and AFC levels declined
      significantly in the bilateral endometrioma group at 1 month postoperatively
      compared with preoperative levels (p < .05) but did not differ significantly at 6
      and 12 months postoperatively. The ovarian stromal pulsatility and resistance
      indices in the ipsilateral ovaries decreased significantly in all patients with
      unilateral ovarian cysts at 6 and 12 months postoperatively compared with
      preoperative levels (p < .05), although the mean ipsilateral ovarian volume was
      significant smaller than the unaffected side. CONCLUSION: There was no detectable
      difference on ovarian reserve marker levels between 4 groups and from baseline
      values at 6 and 12 months after laparoscopic ovarian cystectomy of endometrioma,
      although these levels significantly declined in the first month postoperatively.

PMID- 26210678
TI  - Ovarian cortex transplantation: 60 reported live births brings the success and
      worldwide expansion of the technique towards routine clinical practice.
AB  - This paper describes the success and expansion of ovarian tissue cryopreservation
      and transplantation as a fertility restoration procedure, with the largest series
      of 60 live births worldwide reported. By repeating the procedure, ovarian
      activity can be restored for more than 11 years.

PMID- 26210680
TI  - Response to Fornalski et al.

PMID- 26210679
TI  - Impact of pre-diagnosis behavior on risk of death from esophageal cancer: a
      systematic review and meta-analysis.
AB  - PURPOSE: Most people diagnosed with esophageal cancer will die from their
      disease, but it is not known whether survival is influenced by pre-morbid
      behavior. We undertook a systematic review and meta-analysis to investigate the
      impact of pre-diagnosis behavior on risk of death for esophageal cancer. METHODS:
      We performed a systematic review of studies reporting on the relationship between
      pre-diagnosis smoking, alcohol consumption, overweight and obesity, physical
      activity and regular consumption of nonsteroidal anti-inflammatory drugs, and
      risk of death from esophageal squamous cell carcinoma (ESCC) and adenocarcinomas
      (EACs). Study characteristics are presented and aggregate results are compiled
      using meta-analysis. RESULTS: From an initial pool of 644 non-duplicate records,
      13 articles arising from 12 studies met the inclusion criteria. Considerable
      variation was observed between studies in location, measurement categories,
      adjustment for other risks, and results. Pooled estimates suggested that for ESCC
      pre-diagnosis smoking was associated with a 1.19 times [95 % confidence interval
      (CI) 1.04-1.36] increased risk of death and pre-diagnosis alcohol consumption
      with a 1.36 times increased risk of death (95 % CI 1.15-1.61). No significant
      effects were observed for EAC. We observed a lower risk of death for both ESCC
      and EAC associated with high pre-diagnosis body mass index (BMI) >=25 kg/m(2)
      (ESCC hazard ratio 0.80, 95 % CI 0.67-0.95; EAC 0.80, 95 % CI 0.68-0.95),
      although there was significant heterogeneity across studies. CONCLUSIONS: Our
      findings suggest that a number of modifiable pre-diagnosis risk factors have a
      carryover effect on the risk of death from esophageal cancer. These include
      smoking, drinking alcohol, and BMI.

PMID- 26210681
TI  - A phase 1 study of intermittently administered pazopanib in combination with
      continuous daily dosing of lapatinib in patients with solid tumors.
AB  - PURPOSE: Preclinically, pazopanib/lapatinib combination acted synergistically to
      suppress the activity of multiple tyrosine kinases, including VEGFR-1, 2, 3,
      PDGFR and c-kit (pazopanib), HER1/EGFR and HER2 (lapatinib), and several other
      tyrosine kinases including c-Met through, plausibly, network inhibition effects.
      Clinically, continuous dosing of pazopanib/lapatinib combination was associated
      with a higher response rate than with lapatinib monotherapy, with poor tolerance.
      We explored multiple intermittent dose levels of pazopanib combined with
      continuous daily dosing of lapatinib in patients with solid tumors. METHODS: The
      present study used a phase 1, modified 3 + 3, dose-escalation design to evaluate
      the safety and tolerability of the combination of orally received pazopanib once
      every other day with continuous daily dosing of lapatinib for 28 days. In the
      expansion phase, tumor response was evaluated in patients with specific genetic
      alterations (HER2 amplification, HER2 mutation, c-Met amplification, c-Met
      mutation, and EGFR mutation). RESULTS: Twenty-four patients were treated. The
      most common drug-related adverse events were fatigue 7/24 (29%), skin rash 5/21
      (21%), and diarrhea 3/24 (17%), with 4/24 (16%) patients experiencing grade >=3
      drug-related adverse events. Escalation to the FDA-approved dose (800 mg daily
      for pazopanib and 1500 mg every day for lapatinib) was not feasible due to
      toxicities. Pazopanib 200 mg every other day + lapatinib 500 mg daily was
      considered the maximum tolerated dose (MTD). No tumor response was observed,
      including in patients with the specific molecular genetic alterations tested.
      CONCLUSION: Every other day dosing of pazopanib combined with daily lapatinib was
      tolerated at the established MTD, but no complete or partial tumor responses were
      observed at these dose levels.

PMID- 26210682
TI  - Clinical pharmacology characterization of RG7112, an MDM2 antagonist, in patients
      with advanced solid tumors.
AB  - PURPOSE: RG7112, the first selective small-molecule MDM2 antagonist in clinical
      testing, is a non-genotoxic oral p53 activator. To optimize its dose and
      schedule, a number of clinical pharmacology characteristics were explored in this
      multicenter trial in patients with advanced solid tumors. METHOD: In part 1, the
      impact of high-energy/high-fat meal and formulations (crystalline and amorphous)
      on relative bioavailability was examined in single-dose crossover designs. In
      part 2, schedule optimization (4 schedules of drug administration under fasting
      condition and 2 cohorts with liquid supplementation) was investigated in
      parallel, dose escalation designs. Clinical endpoints were pharmacokinetics (PK),
      pharmacodynamics (PD) including MIC-1 elevation and platelet reduction, and
      safety/tolerability. RESULTS: With a single-dose treatment, a high-fat/high
      energy meal and a new formulation under fasting condition, respectively, enhanced
      overall bioavailability of RG7112 slightly over twofold. Following multiple-dose
      administrations, all four schedules yielded the comparable per-cycle (28-d)
      exposure (AUC), as designed; liquid supplements also enhanced bioavailability.
      High-dose treatments of consecutive daily dosing for 5 and 3 days resulted in
      higher on-treatment-day exposure to RG7112 than both weekly and low-dose/long
      duration (20-day) daily schedules. Serum MIC-1 and blood platelet profiles showed
      similar patterns to those of PK when the clinical pharmacology conditions were
      varied, suggesting the relative importance of treatment-day exposure than overall
      per-cycle AUC. CONCLUSION: Food (both high-fat and low-fat meals) and new
      formulation enhanced bioavailability. High-dose consecutive daily treatment for 3
      5 days is superior to weekly and low-dose/long-duration (20-day) daily schedules
      in yielding the sufficiently high drug exposure and PD effects potentially
      required for cancer treatment efficacy.

PMID- 26210684
TI  - Effects of swimming associated with risedronate in osteopenic bones: An
      experimental study with ovariectomized rats.
AB  - Physical activity and risedronate sodium have effects on metabolic bone diseases,
      maintaining the integrity of bone tissue. Our objective was to evaluate the
      effects of swimming associated with risedronate as a prophylactic means in
      osteopenic bone of ovariectomized rats. A total of 24 animals of the Wistar
      strain were used and separated into four groups containing six animals:
      Ovariectomy (OVX), ovariectomy and swimming (OVXS), ovariectomy and risedronate
      (OVXM), ovariectomy, risedronate and swimming (OVXMS). The effectiveness of the
      treatments were evaluated using the tibia by means of biomechanical,
      radiographic, histomorphometric analyzes. Statistical analysis was performed by
      the non-parametric Kruskal-Wallis test (p<0.05). The OVXM and OVXMS groups showed
      higher values compared to OVX in maximum strength and rigidity. Microscopic
      analysis showed increased trabecular bone in the OVXM group in relation to the
      others, and in the OVXMS compared to OVXS. Proximal densitometry in the OVXM and
      OVXMS groups showed higher values than the OVX and OVXS groups. There were no
      significant differences in overall densitometry. In conclusion, when comparing
      the prophylactic means, risedronate was able to preserve bone mass significantly,
      unlike exercise where an improvement of bone tissue was observed, although not
      significant, and when swimming and risedronate are combined the result was even
      better. 

PMID- 26210683
TI  - Contemporary trends in high-dose interleukin-2 use for metastatic renal cell
      carcinoma in the United States.
AB  - BACKGROUND: Targeted therapies (TTs) have revolutionized metastatic renal cell
      carcinoma (mRCC) treatment in the past decade, largely replacing immunotherapy
      including high-dose interleukin-2 (HD IL-2) therapy. We evaluated trends in HD IL
      2 use for mRCC in the TT era. METHODS: Our cohort comprised a weighted estimate
      of all patients undergoing HD IL-2 treatment for mRCC from 2004 to 2012 using the
      Premier Hospital Database. We assessed temporal trends in HD IL-2 use including
      patient, disease, and hospital characteristics stratified by era (pre-TT uptake:
      2004-2006, uptake: 2007-2009, and post-TT uptake: 2010-2012) and fitted
      multivariable regression models to identify predictors of treatment toxicity and
      tolerability. RESULTS: An estimated 2,351 patients received HD IL-2 therapy for
      mRCC in the United States from 2004 to 2012. The use decreased from 2004 to 2008.
      HD IL-2 therapy became increasingly centralized in teaching hospitals (24% of
      treatments in 2004 and 89.5% in 2012). Most patients who received HD IL-2 therapy
      were men, white, younger than 60 years, had lung metastases, and were otherwise
      healthy. Vasopressors, intensive care unit admission, and hemodialysis were
      necessary in 53.4%, 33.0%, and 7.1%, respectively. Factors associated with
      toxicities in multivariable analyses included being unmarried, male sex, and
      multiple metastatic sites. African Americans and patients with single-site
      metastases were less likely to receive multiple treatment cycles. CONCLUSIONS: HD
      IL-2 therapy is used infrequently for mRCC in the United States, and its
      application has diminished with the uptake of TT. Patients are being increasingly
      treated in teaching hospitals, suggesting a centralization of care and possible
      barriers to access. A recent slight increase in HD IL-2 therapy use likely
      reflects recognition of the inability of TT to effect a complete response.

PMID- 26210685
TI  - Targeting breast cancer-associated fibroblasts to improve anti-cancer therapy.
AB  - In recent years, mass spectrometry-based proteomics has undergone significant
      development steps which may be divided into an exploratory phase, a consolidation
      phase and an application phase. We are in a stage now where we are able to apply
      mass spectrometric technologies to answer complex and clinically relevant
      questions. This is demonstrated here with respect to a current hot topic, namely
      the consideration of the cancer-supporting microenvironment as a target of new
      and more efficient anti-cancer therapy. Actually, the relevance of micro
      environmental stromal cells to tumor initiation and promotion has been clearly
      recognized. However, the individual kind and degree of stroma-derived tumor
      promotion can so far hardly be determined in patients, and hardly any therapeutic
      option exists to dismantle the cancer cells of the stroma-derived support. Quite
      remarkably, the response of stromal cells to standard chemotherapeutics is also
      rather unknown. In this Perspective, experimental strategies how to address such
      issues are outlined in detail. Different cell systems are presented as powerful
      models which allow identifying relevant marker molecules. Targeted proteomics is
      presented as method of choice for both, drug screening in vitro as well as
      monitoring drug responses in patients. By this means, a way of classifying
      different functional tumor promoting mechanisms, evaluating how current treatment
      strategies may affect cancer-associated fibroblasts, identifying effective drugs
      targeting these cancer-associated cells and, may be most importantly,
      demonstrating how combined therapeutic strategies may improve the efficiency of
      anti-cancer treatments are indicated.

PMID- 26210686
TI  - Modification of (137)Cs transfer to rape (Brassica napus L.) phytomass under the
      influence of soil microorganisms.
AB  - After nuclear accidents, such as those experienced in Chernobyl and Fukushima,
      microorganisms may help purify contaminated soils by changing the mobility of
      radionuclides and their availability for plants by altering the physical and
      chemical properties of the substrate. Here, using model experiments with quartz
      sand as a substrate we investigate the influence of microorganisms on (137)Cs
      transfer from substrate to plants. The highest transition of (137)Cs from
      substrate to plants (50% increase compared to the control) was observed after
      Brassica napus L. seeds were inoculated by Azotobacter chroococcum. The best
      results for reducing the accumulation of (137)Cs radionuclides (30% less) were
      noted after the inoculation by Burkholderia sp.. Furthermore, Bacillus megaterium
      demonstrated an increased ability to accumulate (137)Cs. This research improves
      our prediction of the behavior of radionuclides in soil and may contribute
      towards new, microbiological countermeasures for soil remediation following
      nuclear accidents. 

PMID- 26210687
TI  - Transcriptomic response to low salinity stress in gills of the Pacific white
      shrimp, Litopenaeus vannamei.
AB  - The Pacific white shrimp, Litopenaeus vannamei (L. vannamei), is one of the most
      farmed species. Salinity is an important environmental factor that affects its
      growth and distribution. However, the molecular mechanism of the shrimp in
      response to salinity stress remains largely unclear. High-throughput sequencing
      is a helpful tool to analyze the molecular response to salinity challenge in
      shrimp. In the present study, the transcriptomic responses of the gills in L.
      vannamei under low salinity stress were detected by Illumina's digital gene
      expression system. A total of 10,725,789 and 10,827,411 reads were generated from
      the non-changed and low salinity changed groups, respectively. 64,590 Unigenes
      with an average length of 764 bp were generated. Compared with the control, 585
      genes were differentially expressed under low salinity. GO functional analysis
      and KEGG pathway analysis indicated some vital genes in response to the
      challenge. Ten genes related to osmoregulation and ambient salinity adaption were
      selected to validate the DGE results by RT-qPCR. This work provides valuable
      information to study the mechanism of salinity adaption in L. vannamei. Genes and
      pathways from the results will be beneficial to reveal the molecular basis of
      osmoregulation. It also gives an insight into the response to the salinity
      challenge in L. vannamei.

PMID- 26210688
TI  - [Peritoneal tumor pathology - case no. 1: pseudomyxoma peritonei].

PMID- 26210689
TI  - [Peritoneal tumor pathology - case no. 3 : peritoneal well-differentiated
      papillary mesothelioma].

PMID- 26210690
TI  - A afferent fibers are involved in the pathology of central changes in the spinal
      dorsal horn associated with myofascial trigger spots in rats.
AB  - A afferent fibers have been reported to participate in the development of the
      central sensitization induced by inflammation and injuries. Current evidence
      suggests that myofascial trigger points (MTrPs) induce central sensitization in
      the related spinal dorsal horn, and clinical studies indicate that A fibers are
      associated with pain behavior. Because most of these clinical studies applied
      behavioral indexes, objective evidence is needed. Additionally, MTrP-related
      neurons in dorsal root ganglia and the spinal ventral horn have been reported to
      be smaller than normal, and these neurons were considered to be related to A
      fibers. To confirm the role of A fibers in MTrP-related central changes in the
      spinal dorsal horn, we studied central sensitization as well as the size of
      neurons associated with myofascial trigger spots (MTrSs, equivalent to MTrPs in
      humans) in the biceps femoris muscle of rats and provided some objective
      morphological evidence. Cholera toxin B subunit-conjugated horseradish peroxidase
      was applied to label the MTrS-related neurons, and tetrodotoxin was used to block
      A fibers specifically. The results showed that in the spinal dorsal horn
      associated with MTrS, the expression of glutamate receptor
      (mGluR1alpha/mGluR5/NMDAR1) increased, while the mean size of MTrS-related
      neurons was smaller than normal. After blocking A fibers, these changes reversed
      to some extent. Therefore, we concluded that A fibers participated in the
      development and maintenance of the central sensitization induced by MTrPs and
      were related to the mean size of neurons associated with MTrPs in the spinal
      dorsal horn. 

PMID- 26210691
TI  - Programmed cell death protein 1 expression is an independent prognostic factor in
      gastric cancer after curative resection.
AB  - BACKGROUND: Programmed cell death protein 1 (PD-1) and its ligand PD-L1
      downregulate T cell activation and are related to immune tolerance. The aim of
      this study was to clarify the significance of PD-1 and PD-L1 expression and to
      analyze the relationships among PD-1, PD-L1, and Foxp3 expression in gastric
      cancer. METHODS: A total of 105 patients who underwent curative gastrectomy for
      stage II/III gastric cancer were included in this study. PD-1, PD-L1, and Foxp3
      expression were examined by immunohistochemistry and related to prognostic
      factors by univariate and multivariate analyses. RESULTS: PD-1 expression was
      correlated with both PD-L1 and Foxp3 expression. Disease-free survival (DFS) was
      significantly poorer in PD-1-positive patients than in PD-1-negative patients (3
      year DFS, 36.1 % vs. 64.7 %, respectively; p < 0.05). Overall survival also
      tended to be poorer in PD-L1-positive patients than in PD-L1-negative patients.
      Univariate analysis identified sex, T factor, lymphatic invasion, and PD-1
      positivity as significant predictors of poor DFS. Multivariate analysis confirmed
      male sex, lymphatic invasion, and positive PD-1 expression as independent
      prognostic indicators. CONCLUSIONS: PD-1 expression is associated with a poor
      prognosis and is correlated with PD-L1 and Foxp3 expression in patients with
      gastric cancer.

PMID- 26210692
TI  - Efficacy of repeated cytology of pancreatic juice obtained by endoscopic
      nasopancreatic drainage tube for early diagnosis of pancreatic cancer: a case
      series including a case of carcinoma in situ.
AB  - Repeated cytology of pancreatic juice obtained by endoscopic nasopancreatic
      drainage (ENPD) tube has been highlighted as an early diagnostic method for small
      pancreatic cancer, including carcinoma in situ. We report two cases of early
      stage pancreatic cancer diagnosed using repeated cytology; both cases underwent
      curative resection. No significant masses were found on conventional imaging in
      either case, with only pancreatic duct strictures being observed. ENPD tubes were
      placed to collect pancreatic juice in both cases. In case 1, two of five
      pancreatic juice samples showed adenocarcinoma. Therefore, distal pancreatectomy
      was performed, and a PanIN3 grade neoplasm (carcinoma in situ) was identified at
      the branch duct near the distal stricture. In case 2, two of seven pancreatic
      juice samples (collected during the second tube placement) showed adenocarcinoma.
      Therefore, distal pancreatectomy was performed, and a PanIN3 neoplasm was
      identified primarily in the pancreatic duct at a narrow section with fibrosis.
      Partial microinvasion (<1 mm) was observed at the branch duct. Repeated cytology
      of pancreatic juice obtained by ENPD tube is effective for early diagnosis of
      pancreatic cancer, especially in cases without mass formation. However, some
      issues, including the appropriate number of samples, should be addressed in large
      prospective studies. 

PMID- 26210693
TI  - Facilitation of emotion regulation with a single dose of escitalopram: A
      randomized fMRI study.
AB  - Acute antidepressant administration modulates neural activity consistent with
      decreases in negative emotion processing bias. However, studies are yet to
      examine whether treatment facilitates neural activity during reappraisal, an
      adaptive emotion regulation strategy associated with behavioral treatment
      response. Here we examine the impact of acute administration on reappraisal of
      negative stimuli using pharmaco-fMRI. Thirty-six healthy female participants
      completed two sessions of fMRI scanning, separated by a one-week washout period.
      A single dose of the selective serotonin reuptake inhibitor, escitalopram (20mg)
      was administered to participants using a double-blind, randomized, placebo
      controlled crossover design. When participants were administered escitalopram
      (relative to a placebo) and asked to reappraise negative emotional stimuli, left
      amygdala activation was decreased and right inferior frontal gyrus (R IFG)
      activation was increased. Also observed was a greater negative left amygdala-R
      IFG functional connectivity when participants were administered escitalopram
      relative to placebo, and this change in connectivity was associated with
      reductions in subjective ratings of valence and arousal of negative stimuli.
      Further analysis revealed connectivity modulation across multiple frontal
      regions. Results suggest that the acute effect of a commonly prescribed
      antidepressant may include facilitating the regulation of negative emotional
      stimuli, providing new important leads for models of antidepressant action. 

PMID- 26210694
TI  - Meta-cognition is associated with cortical thickness in youth at clinical high
      risk of psychosis.
AB  - Meta-cognition is compromised in people with schizophrenia and people at clinical
      high risk (CHR) of psychosis. In the current work in a CHR sample, we
      hypothesized that meta-cognitive functions would correlate with cortical
      thickness in five brain regions implicated in the pathogenesis of psychosis:
      inferior and middle frontal cortices, anterior cingulate cortex, superior
      temporal cortex and insula. Secondly, we hypothesized that similar neural systems
      would underlie different meta-cognitive functions. Narratives were gathered for
      29 youth at CHR of psychosis using a semi-structured interview. Four meta
      cognitive functions within the narratives were measured with the Meta-cognition
      Assessment Scale and regressed on cortical thickness from our a priori regions of
      interest using FreeSurfer. Mapping statistics from our a priori regions of
      interest revealed that meta-cognition functions were associated with cortical
      thickness in inferior and middle frontal gyri, superior temporal cortex and
      insula. The distribution of cortical thickness was partially similar across the
      four MAS items. Results confirm our hypothesis that cortical thickness is
      significantly associated with meta-cognition in brain regions that consistently
      show gray matter reductions across the schizophrenia spectrum. Evidence for
      thickness covariation in a variety of regions suggests partial dependence in the
      neural architecture underlying various meta-cognitive functions in CHR. 

PMID- 26210696
TI  - Diagnostic value of hydrodistention of the ureteral orifice.
AB  - INTRODUCTION/OBJECTIVE: The dynamic hydrodistention (HD) classification is a
      basic and objective way of rating the ureteral orifice opening. This study
      evaluated the value of hydrodistention of the ureteral orifice in the diagnosis
      of vesicoureteral reflux (VUR). MATERIAL AND METHODS: Between January 2012 and
      March 2013 the HD grade in 106 ureters was prospectively assigned. A 9.5-Fr rigid
      cystoscope with a 0-degree lens was used in all procedures. Warm saline was used
      and the irrigation bag was placed approximately 1 m above the bladder level on
      full flow. The grading is as follows: H0 denotes absence of ureteral dilation; H1
      indicates dilation of the ureteral orifice only; H2 allows visualization of the
      intramural ureter; and H3 allows visualization of the extramural ureter.
      Indications for cystoscopy were endoscopic and open surgical treatment of VUR,
      stent removal, and any other diagnostic reasons. Exclusion criteria were patients
      with: infravesical obstruction, neuropathic bladder, severe detrusor over
      activity/dysfunctional voiding, duplex system, paraureteral diverticulum, bladder
      exstrophy and grade-1 VUR. The 51 refluxing ureters (RUs) were compared with 55
      non-refluxing ureters (NRUs). Finally, sensitivity, specificity, positive and
      negative predictive values, and accuracy rate of HD were evaluated. RESULTS: A
      total of 106 ureters in 61 patients with a mean age of 5.3 +/- 3.9 years (range 2
      months-15 years, median 5 years) were prospectively assigned. The mean HD grade
      in the RUs was 2.17 +/- 0.55. The mean HD grades were 2.0 +/- 0.63, 2.07 +/-
      0.53, 2.38 +/- 0.5 and 2.5 +/- 0.57 for VUR grades 2-5, respectively. The mean HD
      grade in the NRUs was 1.60 +/- 0.70. The HD grades were H0 to H3 in 7.3%, 30.9%,
      56.4% and 5.4% of the NRUs, respectively. The RUs group (2.17 +/- 0.55) showed a
      statistically higher HD grade than the NRUs group (1.60 +/- 0.70) (P < 0.005).
      Sensitivity, specificity, positive and negative predictive values, and accuracy
      rate of HD grading in the diagnosis of VUR were 92%, 38%, 58%, 84%, and 64%,
      respectively. The mean HD grade in contralateral ureters of unilateral VUR was
      1.55 +/- 0.72 and HD grades were H0-H3 in 0%, 55.6%, 33.3% and 11.1% of these
      nine ureters, respectively. In these nine non-refluxing contralateral ureters,
      after endoscopic correction of ipsilateral VUR, new contralateral VUR did not
      occur. CONCLUSION: Even though HD grade was high in the VUR group and popularity
      of the HD grading is on the increase, HD grading by itself still has a low
      diagnostic value.

PMID- 26210695
TI  - Assessment of the Radiation Effects of Cardiac CT Angiography Using Protein and
      Genetic Biomarkers.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether radiation exposure
      from cardiac computed tomographic angiography (CTA) is associated with
      deoxyribonucleic acid (DNA) damage and whether damage leads to programmed cell
      death and activation of genes involved in apoptosis and DNA repair. BACKGROUND:
      Exposure to radiation from medical imaging has become a public health concern,
      but whether it causes significant cell damage remains unclear. METHODS: We
      conducted a prospective cohort study in 67 patients undergoing cardiac CTA
      between January 2012 and December 2013 in 2 U.S. medical centers. Median blood
      radiation exposure was estimated using phantom dosimetry. Biomarkers of DNA
      damage and apoptosis were measured by flow cytometry, whole genome sequencing,
      and single cell polymerase chain reaction. RESULTS: The median dose length
      product was 1,535.3 mGy.cm (969.7 to 2,674.0 mGy.cm). The median radiation dose
      to the blood was 29.8 mSv (18.8 to 48.8 mSv). Median DNA damage increased 3.39%
      (1.29% to 8.04%, p < 0.0001) and median apoptosis increased 3.1-fold
      (interquartile range [IQR]: 1.4- to 5.1-fold, p < 0.0001) post-radiation. Whole
      genome sequencing revealed changes in the expression of 39 transcription factors
      involved in the regulation of apoptosis, cell cycle, and DNA repair. Genes
      involved in mediating apoptosis and DNA repair were significantly changed post
      radiation, including DDB2 (1.9-fold [IQR: 1.5- to 3.0-fold], p < 0.001), XRCC4
      (3.0-fold [IQR: 1.1- to 5.4-fold], p = 0.005), and BAX (1.6-fold [IQR: 0.9- to
      2.6-fold], p < 0.001). Exposure to radiation was associated with DNA damage (odds
      ratio [OR]: 1.8 [1.2 to 2.6], p = 0.003). DNA damage was associated with
      apoptosis (OR: 1.9 [1.2 to 5.1], p < 0.0001) and gene activation (OR: 2.8 [1.2 to
      6.2], p = 0.002). CONCLUSIONS: Patients exposed to >7.5 mSv of radiation from
      cardiac CTA had evidence of DNA damage, which was associated with programmed cell
      death and activation of genes involved in apoptosis and DNA repair.

PMID- 26210697
TI  - Traditionally used medicinal plants against uncomplicated urinary tract
      infections: Are unusual, flavan-4-ol- and derhamnosylmaysin derivatives
      responsible for the antiadhesive activity of extracts obtained from stigmata of
      Zea mays L. against uropathogenic E. coli and Benzethonium chloride as frequent
      contaminant faking potential antibacterial activities?
AB  - The dried stigmata from Zea mays L. are used traditionally for the treatment of
      uncomplicated urinary tract infections. A recent screening has indicated that
      hydroalcoholic extract of the herbal material inhibits the adhesion of
      uropathogenic Escherichia coli (UPEC) to T24 bladder cells. For verification of
      these data EtOH-water (1:1) extracts from 4 different batches of Maydis stigmata
      were investigated. Within an in vitro adhesion assay (UPEC strain 2980 and human
      T24 bladder cells) a dose-dependent antiadhesive activity against UPEC was
      verified (IC50 1040MUg/mL). Bioassay guided fractionation of M. stigmata, batch
      S1, by EtOH-water extraction, followed by chromatography on Sephadex LH20
      revealed two active fractions (I and XI). Further purification of fraction I and
      structure elucidation of the isolated compound revealed the presence of
      significant amounts of the biocide benzethonium chloride as contaminant.
      Benzethonium chloride was also identified in subsequent investigations in 2
      different batches of M. stigmata. The presence of such nondeclared and illegal
      contaminants in the herbal raw material market has to be discussed intensively.
      From benzethonium-free raw material (batch S2) as well as from batch S1 fraction
      XI was further fractionated by MPLC and preparative HPLC, leading to a still
      complex subfraction XIG, which was analyzed by UHPLC/+ESI-QTOF-MS analysis.
      Advanced data processing and species-metabolite relationship database revealed
      the tentatively existence of the unusual C-glycosidic flavones derhamnosylmaysin
      (6), 3'-deoxyrhamnosylmaysin (4), 3'-O-methylderhamnosylmaysin (3), apiferol (2)
      and alternanthin (8) which might be related to the antiadhesive activity of this
      subfraction against UPEC. 

PMID- 26210698
TI  - Development of an immunochromatography assay kit for rapid detection of
      ranavirus.
AB  - Ranaviruses are large, double-stranded DNA viruses of the family Iridoviridae and
      are known to be primary pathogens in frogs, fish and other amphibians. These
      viruses have been shown to be highly adaptable and have the ability to cross
      species barriers, making them a potent threat to global biodiversity. There is
      therefore, a need for rapid and efficient diagnostic methods to control the
      spread of these viruses. To address this, monoclonal antibodies (MAbs) were
      developed against ranavirus strain FV-3 (standard frog virus 3) to detect the
      major capsid protein and FV-3gorf19R related hypothetical protein in both the FV
      3 and KRV-1 (Korean ranavirus) strains. The antibodies were then applied on a
      colloidal gold-immunochromatographic assay (GICA) as a kit for the detection of
      ranaviruses. The kit was able to detect low concentrations of the virus
      (10(1)TCID50/ml) and showed analytical specificity when tested against other
      viral pathogens, including those belonging to the same family. It was possible to
      detect ranavirus in experimentally infected frogs within 30 min using the kit.
      The kit described here is expected to be a valuable and informative tool for on
      site detection of ranavirus in frog.

PMID- 26210699
TI  - Increased sensitivity of RT-PCR for Potato virus Y detection using RNA isolated
      by a procedure with differential centrifugation.
AB  - The sensitivity of reverse transcription-polymerase chain reaction (RT-PCR) for
      virus detection is influenced by many factors such as specificity of primers and
      quality of templates. These factors become extremely important for successful
      detection when virus concentration is low. Total RNA isolated from Potato virus Y
      (PVY)-infected potato plants using the sodium sulfite RNA isolation method or
      RNeasy plant mini kit contains a high proportion of host RNA and may also contain
      trace amount of phenolic and polysaccharide residues, which may inhibit RT-PCR.
      The goal of this study was to enhance the sensitivity of PVY detection by
      reducing host RNA in the extract by differential centrifugation followed by
      extraction using an RNeasy mini kit (DCR method). One-step RT-PCR had relatively
      low amplification efficiency for PVY RNA when a high proportion of plant RNA was
      present. SYBR Green-based real time RT-PCR showed that the RNA isolated by the
      DCR method had a higher cycle threshold value (Ct) for the elongation factor 1
      alpha mRNA (Ef1alpha) of potato than the Ct value of the RNA extracted using the
      RNeasy plant mini kit, indicating that the DCR method significantly reduced the
      proportion of potato RNA in the extract. The detectable amount of RNA extracted
      using the DCR method was <0.001ng when plant sap from 10 PVY-infected and PVY
      free potato leaflets in a 1.5:100 fresh weight ratio was extracted, compared with
      0.01 and 0.02ng of RNA using the RNeasy plant mini kit and sodium sulfite RNA
      isolation methods, respectively. 

PMID- 26210700
TI  - How important are glutathione and thiol reductases to oyster hemocyte function?
AB  - Bivalves are animals with worldwide distribution. Although they play key roles in
      economic activities, human feeding and environmental studies, there is a
      considerable lack of knowledge about the relationship between their immune system
      and antioxidant defenses. Here, we performed an in vitro experiment where
      Crassostrea gigas hemocytes were exposed to the electrophilic compound 1-chloro
      2,4-dinitrobenzene (CDNB, 0.1-50 MUM) for one hour. CDNB treatment clearly
      disturbed thiol homeostasis, causing a concentration-dependent decrease in the
      glutathione (GSH) content and a decrease in the activity of two thiol reductases,
      glutathione reductase (GR - 2.5 and 50 MUM CDNB) and thioredoxin reductase (TrxR 
      only 50 MUM CDNB). The MTT reduction assay showed that none of the CDNB
      concentrations tested significantly altered cell viability. However, there was a
      decrease in the hemocyte's ability to uptake the neutral red dye, which indicates
      lysosomal impairment (>=12.5 MUM CDNB). Cellular immunocompetence was further
      investigated and, despite the lower GSH content, GR activity and impairment in
      lysosome integrity, hemocyte functions (adhesion capacity, phagocytosis of latex
      beads and laminarin-induced ROS production) were preserved in the 2.5 and 12.5
      MUM CDNB treatments. These results suggest a minor importance of thiol pools and
      GR activity in C. gigas hemocyte's immunocompetence, in an in vitro acute
      exposure model. The 50 MUM CDNB treatment, however, significantly compromised all
      the measured hemocyte functions. This response was associated with TrxR
      inhibition, increased lysosome impairment, decreased GSH content, and lower GR
      activity. Therefore, it seems that TrxR may be particularly important for the
      hemocyte function, or, alternatively, it is only affected when a deeply
      aggravated scenario in thiol homeostasis is set up. Such findings point out the
      need for further studies towards a better understanding of antioxidant and immune
      defenses interactions in bivalve cellular systems.

PMID- 26210701
TI  - The acute modulation of norepinephrine on immune responses and genes expressions
      via adrenergic receptors in the giant freshwater prawn, Macrobrachium
      rosenbergii.
AB  - Norepinephrine (NE), immunocompetent parameters (total haemocyte count (THC),
      phenoloxidase (PO) activity, respiratory burst (RB), superoxide dismutase (SOD)
      activity, phagocytic activity and clearance efficiency to Lactococcus garvieae),
      and prophenoloxidase (proPO) system-related genes (lipopolysaccharide- and beta
      1,3-glucan-binding protein, LGBP; prophenoloxidase, proPO; peroxinectin, PE;
      alpha2-macroglobulin, alpha2-M) expressions were investigated in Macrobrachium
      rosenbergii received NE through injection at 50 pmol/prawn after 0, 30, 60, and
      120 min. Furthermore, the PO activity, RB, SOD activity, phagocytic activity and
      proPO system-related genes expressions were determined in haemocytes incubated
      with cacodylate buffer (CAC), NE, and NE co-treated with various adrenergic
      receptor (AR) antagonists in vitro. Results showed that NE, THC, granular cells,
      PO activity, SOD activity, proPO system-related genes expressions, and phagocytic
      activity and clearance efficiency to L. garvieae increased; PO activity per
      granulocyte and RB per haemocyte decreased from 30 to 120 min; semigranular cells
      and RB increased in the initial 30 min, and then decreased at 120 min when the
      prawns received NE by injection. In vitro studies, all the determined immune
      parameters and genes expressions were significantly decreased in haemocytes
      incubated with NE after 30 min. The negative effects of NE were prevented on the
      PO activity and phagocytic activity by the beta-AR antagonist of metoprolol
      (Met), on the SOD activity by the beta-AR antagonist of propranolol (Pro), on the
      RB by the beta-AR antagonist of Met and prazosin (Pra), and on the proPO system
      related genes expressions by alpha-AR antagonist of Pra. These results show that
      NE modulates prawn haemocytes proPO system-related genes expressions via alpha1
      AR, PO activity and phagocytosis via beta1-AR, respiratory burst via alpha1-and
      beta1-ARs, and SOD activity via beta2-AR. It is concluded that NE stimulates the
      regulation of immunocompetence parameters and proPO system-related genes
      expressions in an acute response to maintain homeostasis of M. rosenbergii, which
      is primarily mediated through alpha1-, beta1-and beta2-ARs.

PMID- 26210703
TI  - Turning Physicians Into "Heartwood".

PMID- 26210702
TI  - Maneb disturbs expression of superoxide dismutase and glutathione peroxidase,
      increases reactive oxygen species production, and induces genotoxicity in liver
      of adult mice.
AB  - Maneb (MB), a fungicide largely used in agriculture throughout the world
      including Tunisia, protects many vegetables, fruits and field crops against a
      wide spectrum of fungal diseases. However there is a lack of informations
      regarding the risks arising from MB exposure on non target organisms, especially
      mammals. The aim of this study was to investigate the morphological, biochemical
      and molecular aspects of liver injury after exposure of mice to MB. Four doses of
      MB corresponding to 1/8 (group D1), 1/6 (group D2), 1/4 (group D3), and 1/2
      (group D4) of lethal dose (DL50 = 1500 mg/kg body weight) were administered to
      adult mice. Oxidative stress parameters were also objectified by molecular and
      histological endpoints in the liver. Maneb caused hepatotoxicity as characterized
      by the significant increase in the levels of malondialdehyde and protein
      oxidation marker, advanced oxidation protein products (AOPP). The activities of
      catalase, glutathione peroxidase, superoxide dismutase and the levels of
      glutathione decreased significantly in all treated mice, while vitamin C levels
      decreased only in group D4. We also noted a significant decrease in gene
      expression of superoxide dismutase and glutathione peroxidase enzymes. Maneb
      caused nucleic acids degradation testifying its genotoxicity. Yet, biochemical
      markers in plasma showed a decrease in total protein and an increase in
      aspartate, alanine amino transferases and bilirubin levels in all treatment
      groups. Moreover, plasma levels of cholesterol, triglycerides and low density
      lipoprotein-cholesterol significantly increased, while those of high density
      lipoprotein-cholesterol decreased. These biochemical alterations were correlated
      with significantly histological changes. Our data showed, for the first time,
      that intraperitoneal injection of very high non environmentally relevant MB
      concentrations to adult mice resulted in oxidative stress leading to
      hepatotoxicity and the impairment of defense systems, confirming the pro-oxidant
      and genotoxic effects of this fungicide.

PMID- 26210704
TI  - Long Survival and Severe Toxicity Under 5-Fluorouracil-Based Therapy in a Patient
      With Colorectal Cancer Who Harbors a Germline Codon-Stop Mutation in TYMS.
AB  - We report the first clinical description of a patient with cancer with a
      heterozygous germline codon-stop mutation in the TYMS gene. The mutation
      g.657795_657826del, c.53_84del (NM_001071.2), p.Gln18Argfs*42 causes loss of
      function of one of the TYMS alleles, resulting in a truncated protein. This gene
      codifies for the target enzyme of 5-fluorouracil (5-FU), the basic treatment in
      colorectal cancer. The patient, diagnosed with metastatic colorectal cancer, had
      diarrhea and neutropenia grade 4 and mucositis and neurological toxicity grade 3
      under 5-FU-based therapy and exceeded by more than 50% the average survival after
      metastasectomy. On the basis of the patient's characteristics and the key role of
      TYMS in 5-FU activity, we hypothesize that this mutation may contribute to the
      drug response and toxicities suffered by the patient. 

PMID- 26210705
TI  - 5Hz Repetitive transcranial magnetic stimulation to left prefrontal cortex for
      major depression.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) to left
      prefrontal cortex at 10Hz is the most commonly utilized protocol for major
      depressive disorder (MDD). Published data suggests that left sided 5Hz rTMS may
      be efficacious and well tolerated. OBJECTIVE: We analyzed outcomes in a
      naturalistic cohort of MDD patients who could not tolerate 10Hz rTMS and were
      routinely switched to 5Hz. We hypothesized that the efficacy of 5Hz rTMS would be
      equivalent to 10Hz. METHODS: Records were reviewed for patients (n=98) who
      received 15 or more acute rTMS treatments. The sample was split based upon the
      frequency (10 or 5Hz) at which the majority of treatments were delivered. The
      Inventory of Depressive Symptoms (IDS-SR) and 9-Item Patient Health Questionnaire
      (PHQ-9) were used to evaluate outcomes. RESULTS: Baseline IDS-SR was higher in
      the 5Hz (n=27) than in the 10Hz (n=71) group (p<.05), as was frequency of
      comorbid anxiety (p=.002). Depression outcomes did not differ between groups, and
      there were no differences in response or remission rates (all p>.1). Statistical
      power was sufficient to detect small group differences (d=.26). LIMITATIONS: Open
      label data in a naturalistic setting. CONCLUSION: Outcomes associated with 5Hz
      rTMS did not differ from 10Hz, despite higher baseline depressive symptom
      severity and anxiety in 5Hz patients. 5Hz stimulation may be an alternative
      treatment option for patients unable to tolerate 10Hz rTMS.

PMID- 26210706
TI  - Outcomes with and without axillary node dissection for node-positive lumpectomy
      and mastectomy patients.
AB  - BACKGROUND: American College of Surgeons Oncology Group Z0011 trial of select
      node-positive breast cancer patients demonstrated no survival or recurrence
      differences between SLN/axillary lymph node dissection (ALND) vs SLN. Our
      comparable node-positive lumpectomy and mastectomy populations should have
      similar outcomes. METHODS: An Institutional Review Board approved, retrospective
      review of pathologic SLN (N1) cases was performed. Treatment, recurrence, and
      survival were collected. Statistics was analyzed via exact chi-square test with
      Monte Carlo estimation, Kaplan-Meier curves, and log-rank tests. RESULTS: Of 528
      node-positive patients, 318 patients met criteria: 28 (21.7%) lumpectomy, 32
      (16.9%) mastectomy had SLN; 101 (78.2%) lumpectomy, 157 (83.0%) mastectomy had
      SLN + ALND. Median age was 57.5 years for SLN and 53 years for SLN + ALND (P =
      .003). Mean positive nodes were 1.1 for SLN and 1.47 for SLN + ALND (P = .0018).
      Chemotherapy use differed (SLN = 73.5%, SLN + ALND = 89.7%, P = .0032). Stage and
      recurrence were higher for SLN + ALND (P = .0001, P = .007). No difference in
      comorbidities, nodes retrieved, extracapsular extension, radiation, hormone
      therapy, or overall survival was observed. CONCLUSION: In clinically node
      negative breast cancer patients, ALND for N1 disease has no impact on short-term
      recurrence or survival.

PMID- 26210707
TI  - Improving resident performance on standardized assessments of medical knowledge:
      a retrospective analysis of interventions correlated to American Board of Surgery
      In-Service Training Examination performance.
AB  - BACKGROUND: American Board of Surgery In-Service Training Examination (ABSITE)
      scores are used to assess individual progress and predict board pass rates. We
      reviewed strategies to enhance ABSITE performance and their impact within a
      surgery residency. METHODS: Several interventions were introduced from 2010 to
      2014. A retrospective review was undertaken evaluating these and correlating them
      to ABSITE performance. Analyses of variance and linear trends were performed for
      ABSITE, United States Medical Licensing Examination (USMLEs), mock oral, and mock
      ABSITE scores followed by post hoc analyses if significant. Results were
      correlated with core curricular changes. RESULTS: ABSITE mean percentile
      increased 34% in 4 years with significant performance improvement and increasing
      linear trends in postgraduate year (PGY)1 and PGY4 ABSITE scores. Mock ABSITE
      introduction correlated to significant improvement in ABSITE scores for PGY4 and
      PGY5. Mock oral introduction correlated with significant improvement in PGY1 and
      PGY3. CONCLUSIONS: Our study demonstrates an improvement in mean program ABSITE
      percentiles correlating with multiple interventions. Similar strategies may be
      useful for other programs.

PMID- 26210708
TI  - Intradural Extramedullary Primary Ependymoma of the Craniocervical Junction
      Combined with C1 Partial Agenesis: Case Report and Review of the Literature.
AB  - BACKGROUND: Intramedullary ependymomas represent 40%-60% of spinal cord tumors in
      adults and can be located along the entire spinal cord. Intradural extramedullary
      (IDEM) ependymomas are very rare with the exception of tumors located at the
      filum terminale or conus medullaris, with histologic features of myxopapillary
      ependymomas (World Health Organization grade I). CASE DESCRIPTION: We present the
      case of a 42-year-old woman with an IDEM ependymoma of the craniocervical
      junction who experienced neck pain for 5 months. Magnetic resonance imaging of
      the cervical spine and craniocervical junction showed a large IDEM solid-cystic
      lesion with anterolateral junction spinal cord compression. A preoperative
      computed tomography scan did not show any calcified lesion, although a partial
      agenesis of the C1 posterior arch was observed. During surgery, a well
      encapsulated IDEM tumor without dural attachment or medullary infiltration was
      found, and a total en bloc excision was performed. Histologic examination
      revealed a grade II ependymoma. The patient had an excellent clinical recovery,
      with no recurrence after 2 years of follow-up. CONCLUSIONS: To the best of our
      knowledge, no other cases of craniocervical junction ependymomas with vertebral
      bone abnormalities are described in the literature. This association supports the
      hypothesis that these lesions may originate from the extrusion of ependymal cells
      before neural tube closure. Differential diagnosis should include other
      extramedullary tumors that are more frequent in this region, such as meningioma,
      schwannoma, or dermoid tumor.

PMID- 26210710
TI  - Surgical Anatomy for Control of Ethmoidal Arteries During Extended Endoscopic
      Endonasal or Microsurgical Resection of Vascular Anterior Skull Base Meningiomas.

PMID- 26210709
TI  - Endoscopic-Assisted Posterior Intradural Petrous Apicectomy in Petroclival
      Meningiomas: A Clinical Series and Assessment of Perioperative Morbidity.
AB  - OBJECTIVE: To describe the clinical feasibility and outcome of the endoscopic
      assisted posterior intradural petrous apicectomy approach (PIPA) for petroclival
      meningiomas extending into the supratentorial space. METHODS: From 2005-2013, 29
      patients with a petroclival meningioma underwent tumor removal through a PIPA
      approach. The approach consists of a retrosigmoid approach, intradural anterior
      resection of the petrous apex and microsurgical removal of the tumor, followed by
      endoscopic-assisted visualization and removal of tumor parts in the middle fossa
      or anterior to the brainstem. RESULTS: Patients consisted of 7 men and 22 women;
      the mean age of patients was 52.7 years. In 24 patients, surgery was performed
      with the patient in a semisitting position; in 5 patients, surgery was performed
      with the patient in a supine position. A total resection was achieved in 19
      patients (66%). A Karnofsky performance scale score >60% was recorded in 27
      patients (93%), with surgical complications that involved a cerebrospinal fluid
      leak in 3 patients, bleeding in the surgical cavity in 2 patients, and
      pneumocephalus in 1 patient. The most frequent postoperative neurologic deficit
      was facial palsy (34%), which disappeared or improved consistently in all but 1
      patient, who required a cranial nerve VII-cranial nerve XII anastomosis.
      CONCLUSIONS: For petroclival meningiomas extending into the middle fossa, the
      endoscopic-assisted PIPA approach is safe and straightforward. The principal
      advantages of the PIPA approach are familiarity with the retrosigmoid route; the
      absence of temporal lobe retraction; and early control of the cranial nerves,
      vessels, and brainstem. However, careful patient selection regarding tumor
      extension is fundamental to obtaining optimal outcomes.

PMID- 26210711
TI  - Clinical and Radiological Outcomes After Treatment of Unruptured Paraophthalmic
      Internal Carotid Artery Aneurysms: a Comparative and Pooled Analysis of Single
      Center Experiences.
AB  - OBJECTIVE: Unruptured paraophthalmic aneurysms present unique challenges, and the
      ideal management remains unknown. METHODS: We performed a pooled analysis of
      single-center experiences to compare the risks and effectiveness involving
      patients with unruptured paraophthalmic aneurysms treated with clipping, coiling
      alone, stent-assisted coiling, and flow-diversion. The MEDLINE database was
      searched and thirty-three series (including our institutional experience) were
      included. RESULTS: Clipping caused more intracranial hemorrhage (ICH) and
      neurologic complications (NCs) than coiling alone (ICH: odds ratio [OR] = 3.058,
      P = 0.013; NC: OR = 5.809, P < 0.001), stent-assisted coiling (ICH: P = 0.018;
      NC: OR = 7.367, P < 0.001), and flow-diversion (ICH: P = 0.006; NC: OR = 16.954,
      P < 0.001). Clipping also caused more unfavorable visual outcomes than both
      coiling alone (OR = 3.037, P = 0.001) and stent-assisted coiling (OR = 6.055, P =
      0.005). Clipping resulted in a lower reoperation rate than coiling alone in
      large/giant aneurysm group, which approached statistical significance (OR =
      0.133, P = 0.057). Clipping, stent-assisted coiling, and flow-diversion all
      showed higher occlusion rates compared with coiling alone (OR [clipping vs.
      coiling alone] = 2.852, P <= 0.001; OR [coiling alone vs. stent-assisted coiling]
      = 0.302, P = 0.003; OR [coiling alone vs. flow-diversion] = 0.400, P = 0.013).
      Flow-diversion showed comparative complication rate, clinical outcomes, and
      angiographic result compared with stent-assisted coiling. No significant
      differences were found among all 4 treatment modalities on mortality and poor
      outcome. CONCLUSIONS: Endovascular therapies have benefits over surgical clipping
      in terms of fewer intracranial hemorrhage complications, fewer NCs, and lower
      unfavorable visual outcome rate. Flow diversion showed comparative safety and
      effectiveness to stent-assisted coiling, and they both achieved better radiologic
      results than coiling alone. Further validation by randomized cohort studies is
      still needed to provide robust evidence.

PMID- 26210712
TI  - Role of Subdural Interhemispheric Electrodes in Presurgical Evaluation of
      Epilepsy Patients.
AB  - OBJECTIVE: Surgery is a well-established and safe treatment option for focal drug
      resistant epilepsy. However, difficulties are often encountered in diagnosing
      mesial cortical lesions. The aim of this study was to evaluate the usefulness and
      overall complication rate of subdural interhemispheric electrodes (IHEs) as part
      of an invasive presurgical evaluation of epilepsy patients. METHODS: A total of
      100 patients who underwent implantation of subdural IHE were included in the
      study. Data on surgical complications, subdural electrodes and contacts, benefits
      of invasive electroencephalography recording, and final seizure outcome were
      collected and analyzed. RESULTS: A total of 343 subdural strip electrodes with a
      total of 1470 contacts were implanted. There were 6 perioperative/postoperative
      complications, none of them leading to a permanent neurologic deficit. An
      increased number of IHE (P = 0.005) and IHE-contacts (P = 0.03) also increased
      the rate of focus detection, while not significantly changing complication rate
      (P = 0.26). Two benefits of IHE (focus detection of interhemispheric lesions and
      mapping) in extratemporal resections were significantly associated with excellent
      seizure outcome (ILEA1) (P = 0.03, respectively P < 0.001). Other features
      associated with excellent seizure outcome are pure resections (w/o multiple
      subpial transection, P = 0.006), specific histology (P < 0.001), and a visible
      magnetic resonance imaging lesion (P = 0.002). CONCLUSION: Implantation of IHE
      for the preoperative evaluation of epilepsy patients is an established surgical
      procedure with an acceptable complication profile. The benefits delivered from
      IHE can positively influence final seizure outcome in the challenging group of
      extratemporal resections due to interhemispheric lesions. Thus IHEs demonstrate a
      useful diagnostic utility for the presurgical evaluation of selected epilepsy
      patients.

PMID- 26210713
TI  - Combined Transzygomatic and Pterional Approach for Resection of a Dermoid Cyst of
      the Foreman Ovale.
AB  - Dermoid cysts are rare, benign intracranial lesions commonly located in the
      posterior fossa. We describe a uniquely located dermoid cyst in the foreman ovale
      resected via a combined pterional and transzygomatic approach. 

PMID- 26210714
TI  - Recurrent Perimesencephalic Subarachnoid Hemorrhage After 12 Years: Missed
      Diagnosis, Vulnerable Anatomy, or Random Events?
AB  - BACKGROUND: Perimesencephalic subarachnoid hemorrhage (PMSAH) is a well-defined
      subtype of angiogram-negative SAH, characterized by a benign natural history and
      a virtually nonexistent risk of recurrence. Few case reports of recurrent PMSAH
      exist in the literature, all occurring after relatively short time intervals
      ranging from 5 days to 31 months, mostly in patients on antithrombotic therapy.
      We present a unique case of ultra-late PMSAH recurrence after 12 years, in a
      patient not receiving antithrombotic medications. CASE DESCRIPTION: A woman
      presented with 2 similar episodes of sudden-onset severe headache and neck pain,
      without associated neurologic deficits: a first episode at the age of 48 years
      and a second at 60 years. In each instance, the pattern of hemorrhage was
      consistent with PMSAH, platelet count and coagulation tests were normal, and a
      full etiologic work-up, including CTA, catheter angiography, and magnetic
      resonance imaging, failed to reveal an underlying vascular or tumoral etiology.
      The patient had a favorable clinical course each time. CONCLUSIONS: Although
      exceptional, recurrence of PMSAH is not impossible. If the 2 events are assumed
      to be random and independent of each other, binomial statistics yield
      approximately a 79 per billion chance of 2 or more episodes occurring over an 80
      year lifetime. However, other possibilities should be kept in mind, including
      tiny and radiographically occult vascular lesions or particular venous anatomy
      predisposing patients to recurrent bouts of PMSAH. Patients should not be told
      that the risk of recurrence is zero, but that it is close to zero.

PMID- 26210715
TI  - Treatment of AVM-Associated Epilepsy and the Factors Influencing Outcomes.

PMID- 26210716
TI  - Is Alpha-1 Antichymotrypsin Gene Polymorphism a Risk Factor for Primary
      Intracerebral Hemorrhage? A Case-Control Study and Meta-Analysis.
AB  - BACKGROUND: Alpha-1 antichymotrypsin (ACT) signal peptide A/T polymorphism has
      been suggested to play a role in various brain diseases with arterial wall
      pathology. We conducted a case-control study and a meta-analysis to evaluate the
      association between this polymorphism and risk of primary intracerebral
      hemorrhage. MATERIAL AND METHODS: A total of 188 patients and 200 age- and sex
      matched healthy controls were enrolled in our case-control study. The ACT
      polymorphism was genotyped by PCR-LDR. Further meta-analysis was conducted by
      searching literature from PUBMED, EMBASE, and Chinese National Knowledge
      Infrastructure databases until December 2014, then combining data using
      STATA10.0. RESULTS: Similar genotype distribution was detected between PICH
      patients and healthy controls (p=0.523). Further analysis based on hypertension
      and location of hemorrhage did not observe significant association. Multiple
      logistic regression analysis also failed to identify ACT polymorphism as an
      independent risk factor for PICH. With regard to meta-analysis, a total of 6 case
      control studies including 932 PICH patients and 1140 controls were enrolled.
      Pooled ORs failed to detect a significant association of ACT signal peptide A/T
      polymorphism with PICH (dominant model: OR=1.03, 95%CI=0.72-1.46; recessive
      model: OR=1.08, 95%CI=0.88-1.32). Subgroup analysis based on hypertension
      revealed no association in hypertensive PICH or in normotensive PICH.
      CONCLUSIONS: Our case-control study in a Chinese population did not detect a
      significant association between ACT signal peptide A/T polymorphism and PICH.
      Moreover, meta-analysis combining data from relevant studies failed to provide
      evidence for the association. Further well-designed studies with larger sample
      sizes are warranted to verify our findings.

PMID- 26210717
TI  - Feasibility of various carbon sources and plant materials in enhancing the growth
      and biomass productivity of the freshwater microalgae Monoraphidium griffithii
      NS16.
AB  - In order to assess the feasibility of various carbon sources and plant materials
      in increasing the growth rate and biomass productivity of Monoraphidium
      griffithii, ten carbon sources as well as six plant materials were tested in
      mixotrophic cultures with or without aeration. It was found that glucose,
      fructose, maltose, sodium acetate and mannitol were potential carbon sources for
      growth enhancement of M. griffithii. Supplementation of culture medium with these
      carbon sources resulted in approximately 1-4-fold increase in cell density
      compared to control in a small scale culture. In a larger scale mixotrophic
      culture with aeration, 0.05% mannitol and 0.1% fructose resulted in a decent 1
      1.5-fold increase in final cell density, approximately 2-fold increase in growth
      rate and 0.5-1-fold increase in dry biomass weight. Findings from this study
      suggests that glucose, fructose, maltose and mannitol were potential organic
      carbon sources for mixotrophic culture of M. griffithii.

PMID- 26210718
TI  - Duodenal stump leak following a duodenal switch: A case report.
AB  - INTRODUCTION: Duodenal switch (DS) is a superior choice for surgical weight loss
      in the super obese patient population. However, there is an associated risk of
      adverse events following a DS procedure including vitamin deficiencies, bleeding,
      obstruction, stricture, and leakage. PRESENTATION OF CASE: A 37-year-old female
      with body mass index of 67kg/m(2) and multiple comorbidities underwent a Da Vinci
      assisted, laparoscopic, one-stage, single-anastomosis DS procedure. On
      postoperative day 11, the patient developed persistent nausea, fatigue, and
      severe abdominal pain. She underwent diagnostic laparoscopy and was found to have
      hemoperitoneum, which was evacuated, but active bleeding source was not
      identifiable. Three days later, the patient underwent exploratory laparotomy, for
      bleeding with duodenal stump blowout. DISCUSSION: Duodenal stump blowout is the
      result from increased pressure caused by distal obstruction with the back up of
      duodenal contents. Anastomotic leakage/blow-out following surgery when suspected,
      should be individualized and management strategy should be implemented according
      to the size of the leak, extent of the abscess, and status of the patient.
      CONCLUSION: Duodenal stump leaks must be diagnosed as early as possible, and
      treated appropriately with operative intervention. Regardless of the operative
      technique the key to appropriate treatment is stabilize the patient, repair the
      duodenal stump, and adequate drainage.

PMID- 26210719
TI  - Reversibility of cardiopulmonary impairment after laparoscopic repair of large
      hiatal hernia.
AB  - Giant hiatus hernia with or without intrathoracic gastric volvulus often presents
      with symptoms suggestive of both cardiac and pulmonary compression.
      Cardiopulmonary impairment may be reversible in these patients by laparoscopic
      crural repair and fundoplication as shown in this case report. Cardiac magnetic
      resonance and the cardiopulmonary exercise test may help selecting patients for
      surgery. These preliminary findings led us to start a prospective study using
      this multimodality diagnostic approach. 

PMID- 26210720
TI  - Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.
AB  - Astrocytes, the most versatile cells of the central nervous system, play an
      important role in the regulation of neurotransmitter homeostasis, energy
      metabolism, antioxidant defenses and the anti-inflammatory response. Recently,
      our group characterized cortical astrocyte cultures from adult Wistar rats. In
      line with that work, we studied glial function using an experimental in vitro
      model of aging astrocytes (30 days in vitro after reaching confluence) from
      newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic
      parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and
      glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and
      AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1
      expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS
      activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an
      increase in GSH levels, along with an increase in xCT expression. NB, AD and AG
      astrocytes presented similar morphology; however, differences in GFAP levels were
      observed. Taken together, these results improve the knowledge of cerebral
      senescence and represent an innovative tool for brain studies of aging. 

PMID- 26210722
TI  - Periodontal Disease and CKD-Associated Morbidity: Is There Now Enough Evidence to
      Move From Observation to Intervention?

PMID- 26210723
TI  - CKD in the Elderly: Kidney Senescence or Blood Pressure-Related Nephropathy?

PMID- 26210724
TI  - Treated and Untreated Kidney Failure: Quantifying an Outcome.

PMID- 26210725
TI  - Gait Speed in Patients With Kidney Failure Treated With Long-term Dialysis.

PMID- 26210726
TI  - AJKD Atlas of Renal Pathology: Minimal Change Disease.

PMID- 26210727
TI  - A Home Visit, Is It?

PMID- 26210728
TI  - Quiz Page August 2015: Leukemoid Reaction and Acute Kidney Injury Following
      Kidney Transplantation.

PMID- 26210729
TI  - AJKD Atlas of Renal Pathology: Focal Segmental Glomerulosclerosis.

PMID- 26210730
TI  - AJKD Atlas of Renal Pathology: Collapsing Glomerulopathy.

PMID- 26210731
TI  - AJKD Atlas of Renal Pathology: Tip Lesion Variant of Focal Segmental
      Glomerulosclerosis.

PMID- 26210732
TI  - AJKD Atlas of Renal Pathology: Cellular Variant of Focal Segmental
      Glomerulosclerosis.

PMID- 26210733
TI  - AJKD Atlas of Renal Pathology: Hilar Variant of Focal Segmental
      Glomerulosclerosis.

PMID- 26210735
TI  - Independent and combined associations of risky single-occasion drinking and
      drinking volume with alcohol use disorder: Evidence from a sample of young Swiss
      men.
AB  - BACKGROUND: Risky single-occasion drinking (RSOD) is a prevalent and potentially
      harmful alcohol use pattern associated with increased alcohol use disorder (AUD).
      However, RSOD is commonly associated with a higher level of alcohol intake, and
      most studies have not controlled for drinking volume (DV). Thus, it is unclear
      whether the findings provide information about RSOD or DV. This study sought to
      investigate the independent and combined effects of RSOD and DV on AUD. METHODS:
      Data were collected in the longitudinal Cohort Study on Substance Use Risk
      Factors (C-SURF) among 5598 young Swiss male alcohol users in their early
      twenties. Assessment included DV, RSOD, and AUD at two time points. Generalized
      linear models for binomial distributions provided evidence regarding associations
      of DV, RSOD, and their interaction. RESULTS: DV, RSOD, and their interaction were
      significantly related to the number of AUD criteria. The slope of the interaction
      was steeper for non/rare RSOD than for frequent RSOD. CONCLUSIONS: RSOD appears
      to be a harmful pattern of drinking, associated with increased AUD and it
      moderated the relationship between DV and AUD. This study highlighted the
      importance of taking drinking patterns into account, for both research and public
      health planning, since RSO drinkers constitute a vulnerable subgroup for AUD.

PMID- 26210734
TI  - Differences in alcohol use and alcohol-related problems between transgender- and
      nontransgender-identified young adults.
AB  - BACKGROUND: Little is known about differences in alcohol use and alcohol-related
      problems between transgender- and nontransgender-identified populations. Using
      data from a large-scale health survey, we compare the drinking patterns and
      prevalence of alcohol-related problems of transgender-identified individuals to
      nontransgender-identified males and females. For transgender-identified people,
      we examine how various forms of victimization relate to heavy episodic drinking
      (HED). METHODS: Cross-sectional surveys were completed by 75,192 students aged 18
      29 years attending 120 post-secondary educational institutions in the United
      States from 2011 to 2013. Self-reported measures included alcohol use, alcohol
      related problems, victimization, and sociodemographics, including 3 gender
      identity groups: transgender-identified individuals; nontransgender-identified
      males; and nontransgender-identified females. RESULTS: Compared to transgender
      identified individuals, nontransgender-identified males were more likely to
      report HED in the past 2 weeks (relative risk=1.42; p=0.006); however,
      nontransgender-identified males and females reported HED on fewer days than
      transgender-identified people (incidence-rate ratios [IRRs] ranged from 0.28 to
      0.43; p-values<0.001). Compared to transgender-identified people, nontransgender
      identified males and females had lower odds of past-year alcohol-related sexual
      assault and suicidal ideation (odds ratios ranged from 0.24 to 0.45; p
      values<0.05). Among transgender-identified people, individuals who were sexually
      assaulted (IRR=3.21, p=0.011) or verbally threatened (IRR=2.42, p=0.021) in the
      past year had greater HED days than those who did not experience those forms of
      victimization. CONCLUSIONS: Compared to transgender-identified people,
      nontransgender-identified males and females: have fewer HED occasions (despite
      nontransgender-identified males having greater prevalence of HED); and are at
      lower risk for alcohol-related sexual assaults and suicidal ideation. Experiences
      of sexual assault and verbal threats are associated with greater HED occasions
      for transgender-identified people.

PMID- 26210736
TI  - Factors associated with substance use treatment completion in residential
      facilities.
AB  - PURPOSE: Individuals in residential treatment often face many challenges, which
      can include limited education, unstable housing, difficulty participating in the
      workforce, and severe substance use problems. We analyzed factors associated with
      substance use treatment completion. We focused on factors that can be influenced
      by health care system changes resulting from the Affordable Care Act (ACA). DATA
      AND METHODS: We used the 2010 Treatment Episode Data Set - Discharges (TEDS-D),
      which is made available by the Substance Abuse and Mental Health Services
      Administration (SAMHSA). We analyzed factors associated with substance use
      treatment completion using logistic regression. RESULTS: Individuals in
      residential treatment were often unemployed or not in the labor force, had prior
      substance use treatment episodes, used more than one substance, and were
      uninsured. Factors associated with treatment completion included older age,
      greater education, employment, criminal justice referral, not being homeless, and
      private insurance. CONCLUSION: The expansion in private insurance coverage as a
      result of the ACA may result in more treatment completion in residential
      settings. Changes to the Medicaid program resulting from the ACA, including
      coverage of substance use treatment as an essential health benefit and greater
      support for housing, education, and employment, may also contribute to more
      residential discharges ending in treatment completion.

PMID- 26210737
TI  - Individual differences in effects of child care quality: The role of child
      affective self-regulation and gender.
AB  - The current study investigated whether the relation between child care quality
      and children's socio-emotional behavior depended on children's affective self
      regulation skills and gender. Participants were 545 children (Mage=27 months)
      from 60 center-based child care centers in the Netherlands. Multi-level analyses
      showed that children with low affective self-regulation skills or who were male
      demonstrated less teacher-rated social competence when exposed to relatively low
      quality child care. In addition, children with low affective self-regulation
      skills also showed more social competence in the case of relatively high quality
      child care, suggesting mechanisms of differential susceptibility. No main effects
      of child care quality or interactions were found for teacher- and parent-rated
      externalizing behavior. These findings emphasize the importance of considering
      children's affective self-regulation skills and gender in understanding the
      effects of child care quality. High quality child care can be a means to
      strengthen children's social development. 

PMID- 26210738
TI  - Cloning and characterization of microsomal triglyceride transfer protein gene and
      its potential connection with peroxisome proliferator-activated receptor (PPAR)
      in blunt snout bream (Megalobrama amblycephala).
AB  - Microsomal triglyceride transfer protein (MTTP), a major intracellular protein
      capable of transferring neutral lipids, plays a pivotal role in the assembly and
      secretion of apolipoprotein B-containing lipoproteins. In this study, MTTP cDNA
      was firstly cloned from the liver of blunt snout bream (Megalobrama
      amblycephala), the full-length cDNA covered 3457-bp with an open reading frame of
      2661-bp, which encodes 886 amino acids, including a putative signal peptide of 24
      amino acids long. After the feeding trial, a graded tissue-specific expression
      pattern of MTTP was observed and high expression abundance in the liver and
      intestine indicated its major function in lipid transport in this fish species.
      In addition, expression of genes encoding MTTP as well as peroxisome proliferator
      activated receptor (PPAR), which are transcription factors and serve as key
      regulators in lipid homoeostasis, was all affected by dietary lipid and choline
      supplementations. Elevated dietary lipid levels significantly increased the
      liver, intestinal and muscle MTTP mRNA abundance. Additionally, the down
      regulation of MTTP expression in the liver and muscle was observed when fish were
      fed with inadequate choline supplementation in high-fat diet, yet up-regulated as
      supplementing extra choline in diet. Expressions of PPARalpha and PPARbeta in the
      liver and muscle showed similar trend of MTTP expression. The results suggested
      the potential connection of MTTP and PPAR in response to different dietary
      nutritional factors. Furthermore, extra choline supplementations could promote
      lipid transfer and enhance fatty acid oxidation, which indicated a molecular
      mechanism of choline on diminishing fat accumulation in blunt snout bream. 

PMID- 26210740
TI  - Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile
      acids.
AB  - Although epidemiological evidence in humans and bile acid feeding studies in
      rodents implicate bile acids as tumor promoters, the role of endogenous bile
      acids in colon carcinogenesis remains unclear. In this study, we exploited mice
      deficient in the ileal apical sodium-dependent bile acid transporter (ASBT,
      encoded by SLC10A2) in whom fecal bile acid excretion is augmented more than 10
      fold. Wild-type and Asbt-deficient (Slc10a2 (-/-) ) male mice were treated with
      azoxymethane (AOM) alone to examine the development of aberrant crypt foci, the
      earliest histological marker of colon neoplasia and a combination of AOM and
      dextran sulfate sodium to induce colon tumor formation. Asbt-deficient mice
      exhibited a 54% increase in aberrant crypt foci, and 70 and 59% increases in
      colon tumor number and size, respectively. Compared to littermate controls, Asbt
      deficient mice had a striking, 2-fold increase in the number of colon
      adenocarcinomas. Consistent with previous studies demonstrating a role for
      muscarinic and epidermal growth factor receptor signaling in bile acid-induced
      colon neoplasia, increasing bile acid malabsorption was associated with M3
      muscarinic and epidermal growth factor receptor expression, and activation of
      extracellular signal-related kinase, a key post-receptor signaling molecule.

PMID- 26210741
TI  - PIWI-interacting RNA 021285 is involved in breast tumorigenesis possibly by
      remodeling the cancer epigenome.
AB  - Although PIWI-interacting RNAs (piRNAs) account for the largest class of the
      small non-coding RNA superfamily, virtually nothing is known of their function in
      human carcinogenesis. Once thought to be expressed solely in the germ line where
      they safeguard the genome against transposon-induced insertional mutations,
      piRNAs are now believed to play an active role in somatic gene regulation through
      sequence-specific histone modification and DNA methylation. In the current study,
      we investigate the role of piRNA-021285 (piR-021285) in the regulation of the
      breast cancer methylome. Genotypic screening of a panel of single-nucleotide
      polymorphism (SNP)-containing piRNAs revealed a significant association between
      SNP rs1326306 G>T in piR-021285 and increased likelihood for breast cancer in a
      Connecticut-based population (441 cases and 479 controls). Given nascent but
      compelling evidence of piRNA-mediated gene-specific methylation in the soma, a
      genome-wide methylation screen was then carried out using wild type (WT) and
      variant piR-021285 mimic-transfected MCF7 cells to explore whether the observed
      association could be attributed in part to piR-021285-induced methylation at
      cancer-relevant genes. We found significant methylation differences at a number
      of experimentally implicated breast cancer-related genes, including attenuated 5'
      untranslated region (UTR)/first exon methylation at the proinvasive ARHGAP11A
      gene in variant mimic-transfected cells. Follow-up functional analyses revealed
      both concurrent increased ARHGAP11A mRNA expression and enhanced invasiveness in
      variant versus WT piR-021285 mimic-transfected breast cancer cell lines. Taken
      together, our findings demonstrate the first evidence supporting a role of
      piRNAs, a novel group of non-coding RNA, in human tumorigenesis via a piRNA
      mediated epigenetic mechanism, which warrants further confirmation and
      investigation. 

PMID- 26210742
TI  - Kruppel-like factor 9 (KLF9) prevents colorectal cancer through inhibition of
      interferon-related signaling.
AB  - Expression of the transcription factor Kruppel-like factor 9 (KLF9) is frequently
      reduced in colorectal cancers, although a tumor suppressive role has not been
      established. To determine if KLF9 suppresses intestinal adenoma formation, we
      generated mice of distinct Klf9 genotypes in the background of the Apc (Min/+)
      mouse and compared their adenoma burdens at 16 weeks of age. While small
      intestine adenoma burden remained unchanged among Klf9 genotypes, male and female
      Apc(Min/+)/Klf9(-/-) and Apc(Min/+)/Klf9(+/-) mice exhibited significantly more
      colon adenomas than their Apc(Min/+)/Klf9(+/+) counterparts. Microarray analysis
      showed significant increases in the expression of interferon-induced genes in the
      colon mucosa of female Apc (Min/+)/Klf9(+/-) and Apc(Min/+)/Klf9(-/-) compared to
      Apc(Min/+)/Klf9(+/+) mice, prior to overt adenoma occurrence. Gene upregulation
      was confirmed by qPCR of colon mucosa and by siRNA knockdown of KLF9 in human
      HT29 colorectal cancer cells. Increases in expression of these genes were further
      augmented by supplementation with Interferon beta1. Circulating levels of the
      cytokine, interferon-stimulated gene 15 (ISG15) were increased in
      Apc(Min/+)/Klf9(+/-) and Apc(Min/+)/Klf9(-/-) mice relative to
      Apc(Min/+)/Klf9(+/+). Additionally, colon mucosal levels of ISG15 were increased
      in Apc(Min/+)/Klf9(+/-) mice. Chromatin immunoprecipitation demonstrated KLF9
      recruitment to the ISG15 promoter. Lastly, treatment with ISG15 suppressed
      apoptosis in HT29 cells, in the presence and absence of 5-fluorouracil (5FU).
      Results show KLF9 to be a haploinsufficient suppressor of colon tumorigenesis in
      Apc(Min/+) mice in part, by repression of ISG15 and the latter's antiapoptotic
      function. SUMMARY: Kruppel-like factor 9 (KLF9) is a haploinsufficient tumor
      suppressor in the ApcMin/+ mouse colon by suppressing expression of ISG15, an
      apoptosis-inhibiting cytokine.

PMID- 26210743
TI  - Analysis of 32 toxic natural substances in herbal products by liquid
      chromatography quadrupole linear ion trap mass spectrometry.
AB  - In this study, an LC-MS/MS EPI method was developed for simultaneous
      determination of 32 toxic natural substances in herbal products. The analytes
      include aconite alkaloids, lobelia alkaloids, solanaceous alkaloids, digitalis
      steroid glycosides, strychnine, tetrahydropalmatine etc. They werecommonly used
      in herbal products. The target analytes were extracted from the samples using
      theQuEChERS method and analysed using AB SCIEX QTRAP 5500 coupled with Agilent
      HPLC 1260. Thecolumn used was biphenyl reversed phase analytical column. Mobile
      phase A and B were deionizedwater and methanol respectively, both containing 5mM
      ammonium formate and 0.1% formic acid. TheMRM-IDA-EPI method enabled
      quantification and confirmation of the analytes in a single run. The EPIwas used
      for the qualitative analysis while the MRM was used for the quantitative
      analysis. Limits ofdetection were determined to be below 10MUg/kg for the
      majority of the analytes. The recoveries forthose commonly detected natural
      substances were in the acceptable range of 70-120%.

PMID- 26210744
TI  - A UHPLC-TOF/MS method based metabonomic study of total ginsenosides effects on
      Alzheimer disease mouse model.
AB  - A metabonomic method was established to find potential biomarkers and study the
      metabolism disturbance in Alzheimer disease animal model. Total ginsenosides, as
      potential agent in neuroprotection and anti-inflammation, was also studied to
      learn the regulation mechanism to plasma metabolites in model animals. In
      experiment, amyloid beta 1-42 was occupied to form Alzheimer disease animal
      model. After drug administration, animals were evaluated by Morris water maze
      behavior test and sacrificed. Plasma samples were then analyzed using UHPLC
      TOF/MS method to determine the endogenous metabolites. Behavior test results
      revealed that the spatial learning and memory abilities were deficit in model
      mice, and total ginsenosides could improve cognition abilities in dose-dependent
      manners. Principal component analysis showed that model and sham were divided
      into two groups, which means the metabolic network of mice was disturbed after
      modeling. Accordingly, 19 biomarkers were found and identified. In model group,
      the levels of proline, valine, tryptophan, LPC (14:0), LPC (15:0), LPC (15:1),
      LPC (17:0), LPC (18:2), LPC (18:3) and LPC (20:4) were up-regulated, while the
      levels of acetylcarnitine, palmitoylcarnitine, vaccenylcarnitine,
      phytosphingosine, N-eicosanoylethanolamine, hexadecenoic acid, docosahexaenoic
      acid, docosapentaenoic acid and octadecadienoic acid were down-regulated. The
      levels of these metabolites were recovered in different degrees after total
      ginsenosides administration. Combining with behavior study results, total
      ginsenosides could ameliorate both cognition symptoms and metabolic changes in
      model animals. This metabonomic approach provided a feasible way to understand
      the endogenous alterations of AD and to study the pharmacodynamic activity of
      novel agents.

PMID- 26210745
TI  - Phenylalanine hydroxylase deficiency in south Italy: Genotype-phenotype
      correlations, identification of a novel mutant PAH allele and prediction of BH4
      responsiveness.
AB  - We investigated the mutation spectrum of the phenylalanine hydroxylase gene (PAH)
      in a cohort of patients from 33 Italian PKU families. Mutational screening of the
      known coding region, including conventional intron splice sites, was performed by
      direct sequencing of the patients' genomic DNA. Thirty-three different disease
      causing mutations were identified in our patient group, including 19 missense, 6
      splicing, 3 nonsense, 5 deletions, with a detection rate of 100%. The most
      prevalent mutation was the IVS10-11G>A, accounting for 12.1% of PKU alleles
      studied. Other frequent mutations were: p.R261Q (9.1%), p.P281L (7.6%), and
      p.R408W (6.1%). We also identified one novel missense mutation, p.H290Q. A
      spectrum of 31 different genotypes was observed and a genotype based predictions
      of BH4-responsiveness were assessed. Among all genotypes, 13 were predicted to be
      BH4-responsive represented by thirteen PKU families. In addition, genotype
      phenotype correlations were performed. This study reveals the importance of a
      full genotyping of PKU patients and the prediction of BH4-responsiveness, not
      only because of the definitive diagnosis and prediction of the optimal diet, but
      also to point out those patients that could benefit from new therapeutic
      approach. They may potentially benefit from BH4 therapy which, combined with a
      less strict diet, or eventually in special cases as monotherapy, may contribute
      to reduce nutritional deficiencies and minimize neurological and psychological
      dysfunctions. 

PMID- 26210746
TI  - Physiologically-based pharmacokinetic modelling of distribution, bioaccumulation
      and excretion of POPs in Greenland sledge dogs (Canis familiaris).
AB  - We used PBPK (physiologically-based pharmacokinetic) modelling to investigate
      distribution, bioaccumulation and excretion of the seven POPs (persistent organic
      pollutants) CB-99, CB-153, HCB, oxychlordane, p,p'-DDE, BDE-47 and BDE-99 in 4
      adult captive Greenland sledge dog (Canis familiaris) bitches fed minke whale
      (Balaenoptera acuterostrata) blubber for 500-635 days. The PBPK modelled POP
      concentrations in adipose tissue, liver, kidney and plasma were mostly within a
      factor 2 of actual measured tissue levels even for those at the lower
      concentration end. The excretion route for oxychlordane and CB-153 was modelled
      to be via faeces while lung alveolar excretion dominated for BDE-47, BDE-99, HCB,
      p,p'-DDE and CB-99. Furthermore the model suggested the retained mass of POPs
      after 500 and 635 days of exposure, respectively, to be relatively low despite
      these POPs being highly recalcitrant. The retention increased in the following
      order (% of total intake); p,p'-DDE (1%)<BDE-47 (6%)<CB-99 (14%)<HCB (16%)<CB-153
      (18%)<BDE-99 (26%)<oxychlordane (34%). Overall; these results indicate that PBPK
      modelling may be a strong tool in risk assessment of POPs in arctic mammals.

PMID- 26210747
TI  - The parasexual lifestyle of Candida albicans.
AB  - Candida albicans is both a prevalent human commensal and the most commonly
      encountered human fungal pathogen. This lifestyle is dependent on the ability of
      the fungus to undergo rapid genetic and epigenetic changes, often in response to
      specific environmental cues. A parasexual cycle in C. albicans has been defined
      that includes several unique properties when compared to the related model yeast,
      Saccharomyces cerevisiae. Novel features include strict regulation of mating via
      a phenotypic switch, enhanced conjugation within a sexual biofilm, and a program
      of concerted chromosome loss in place of a conventional meiosis. It is expected
      that several of these adaptations co-evolved with the ability of C. albicans to
      colonize the mammalian host. 

PMID- 26210748
TI  - Spatial and temporal variation of an ice-adapted predator's feeding ecology in a
      changing Arctic marine ecosystem.
AB  - Spatial and temporal variation can confound interpretations of relationships
      within and between species in terms of diet composition, niche size, and trophic
      position (TP). The cause of dietary variation within species is commonly an
      ontogenetic niche shift, which is a key dynamic influencing community structure.
      We quantified spatial and temporal variations in ringed seal (Pusa hispida) diet,
      niche size, and TP during ontogeny across the Arctic-a rapidly changing
      ecosystem. Stable carbon and nitrogen isotope analysis was performed on 558 liver
      and 630 muscle samples from ringed seals and on likely prey species from five
      locations ranging from the High to the Low Arctic. A modest ontogenetic diet
      shift occurred, with adult ringed seals consuming more forage fish (approximately
      80 versus 60 %) and having a higher TP than subadults, which generally decreased
      with latitude. However, the degree of shift varied spatially, with adults in the
      High Arctic presenting a more restricted niche size and consuming more Arctic cod
      (Boreogadus saida) than subadults (87 versus 44 %) and adults at the lowest
      latitude (29 %). The TPs of adult and subadult ringed seals generally decreased
      with latitude (4.7-3.3), which was mainly driven by greater complexity in trophic
      structure within the zooplankton communities. Adult isotopic niche size increased
      over time, likely due to the recent circumpolar increases in subarctic forage
      fish distribution and abundance. Given the spatial and temporal variability in
      ringed seal foraging ecology, ringed seals exhibit dietary plasticity as a
      species, suggesting adaptability in terms of their diet to climate change. 

PMID- 26210749
TI  - Sexual dysfunction is associated with postural instability gait difficulty
      subtype of Parkinson's disease.
AB  - The pathophysiology of the postural instability gait difficulty (PIGD) subtype of
      Parkinson's disease (PD) is unclear. Information on the spectrum of non-motor
      symptoms (NMS) in PIGD phenotype is limited. Our objective is to compare the
      spectrum of NMS in PIGD subtype compared to non-PIGD subgroup in PD patients and
      to determine predictive factors that are associated with PIGD phenotype. A total
      of 432 PD patients comprising 158 PIGD and 274 non-PIGD patients were recruited.
      NMS burden (frequency and severity) was assessed using non-motor symptom scale
      (NMSS). In the univariable analysis, NMSS total score (P = 0.0132), NMSS domain 3
      (mood/apathy) score (P = 0.0108), NMSS domain 5 (attention/memory) score (P =
      0.0048) and NMSS domain 8 (sexual function) score (P = 0.0052) were significantly
      higher in the PIGD group than in the non-PIGD group. Using multivariable logistic
      regression, UPDRS tremor score, UPDRS PIGD score, H&Y staging score and NMSS
      domain 8 (sexual function) score were found to be significantly different in the
      PIGD group compared to the non-PIGD group. We disclosed for the first time that
      PIGD patients demonstrated a greater overall NMS burden and sexual dysfunction
      and was an independent predictor of PIGD phenotype. Early intervention of sexual
      dysfunction symptoms in PIGD patients may improve their clinical management. 

PMID- 26210739
TI  - The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)
      Waves 1 and 2: review and summary of findings.
AB  - PURPOSE: The NESARC, a "third-generation" psychiatric epidemiologic survey that
      integrated detailed measures of alcohol and drug use and problems has been the
      data source for over >850 publications. A comprehensive review of NESARC findings
      and their implications is lacking. METHOD: NESARC was a survey of 43,093
      participants that covered alcohol, drug and psychiatric disorders, risk factors,
      and consequences. Wave 1 of the NESARC was conducted in 2001-2002. Three years
      later, Wave 2 follow-up re-interviews were conducted with 34,653 of the original
      participants. Scopus and Pubmed were used to search for NESARC papers, which were
      sorted into topic areas and summarized. RESULT: The most common disorders were
      alcohol and posttraumatic stress disorders, and major depression. Females had
      more internalizing disorders and males had more externalizing disorders, although
      the preponderance of males with alcohol disorders (the "gender gap") was less
      pronounced than it was in previous decades. A race/ethnic "paradox" (lower risk
      among disadvantaged minorities than whites) remains unexplained. Younger
      participants had higher risk for substance and personality disorders, but not
      unipolar depressive or anxiety disorders. Psychiatric comorbidity was extensive
      and often formed latent trans-diagnostic domains. Since 1991-1992, risk for
      marijuana and prescription drug disorders increased, while smoking decreased,
      although smoking decreases were less pronounced among those with comorbidity. A
      nexus of comorbidity, social support, and stress predicted transitions in
      diagnostic status between Waves 1 and 2. Childhood maltreatment predicted
      psychopathology. Alcohol and drug use disorders were seldom treated; attitudinal
      barriers (little perceived need, perceived alcoholism stigma, pessimism about
      efficacy) were more important in predicting non-treatment than financial
      barriers. CONCLUSIONS: Understanding comorbidity and the effects of early
      stressors will require research incorporating biologic components, e.g., genetic
      variants and brain imaging. The lack of treatment for alcohol and drug disorders,
      predicted by attitudinal rather than financial variables, suggests an urgent need
      for public and professional education to reduce the stigma associated with these
      disorders and increase knowledge of treatment options.

PMID- 26210750
TI  - Effects of soluble guanylate cyclase activation on heart transplantation in a rat
      model.
AB  - BACKGROUND: The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic
      guanosine monophosphate (cGMP) pathway is an important key mechanism to protect
      the heart from ischemia/reperfusion injury. However, this pathway is disrupted in
      several cardiovascular diseases as a result of decreased NO bioavailability and
      increased NO-insensitive forms of sGC. Cinaciguat preferentially activates these
      NO-insensitive, oxidized forms of sGC. METHODS: We assessed the hypothesis that
      targeting NO-unresponsive sGC would protect the graft against
      ischemia/reperfusion injury in a rat heart transplantation model. Before
      explantation, donor Lewis rats received methylcellulose (1%) vehicle or
      cinaciguat 10 mg/kg. The hearts were excised, stored in cold preservation
      solution, and heterotopically transplanted. We evaluated in vivo left ventricular
      function of the graft. RESULTS: After transplantation, decreased left ventricular
      systolic pressure (77 +/- 3 mm Hg vs 123 +/- 13 mm Hg, p < 0.05), dP/dt(max)
      (1,703 +/- 162 mm Hg vs 3,350 +/- 444 mm Hg, p < 0.05), and dP/dt(min) (995 +/-
      110 mm Hg vs 1,925 +/- 332 mm Hg, p < 0.05) were significantly increased by
      cinaciguat. Coronary blood flow was significantly higher in the cinaciguat group
      compared with the control group. Additionally, cinaciguat increased adenosine
      triphosphate levels (1.9 +/- 0.4 umol/g vs 6.6 +/- 0.8 umol/g, p < 0.05) and
      improved energy charge potential. After transplantation, increased c-jun
      messenger RNA expression was downregulated, whereas superoxide dismutase-1 and
      cytochrome-c oxidase mRNA levels were upregulated by cinaciguat. Cinaciguat also
      significantly decreased myocardial DNA strand breaks induced by
      ischemia/reperfusion during transplantation and reduced death of cardiomyocytes
      in a cellular model of oxidative stress. CONCLUSIONS: By interacting with NO
      unresponsive sGC, cinaciguat enhances the protective effects of the NO/cGMP
      pathway at different steps of signal transduction after global myocardial
      ischemia/reperfusion. Its clinical use as pre-conditioning agent could be a novel
      approach in cardiac surgery.

PMID- 26210751
TI  - Ventricular assist devices in a contemporary pediatric cohort: Morbidity,
      functional recovery, and survival.
AB  - BACKGROUND: Limited availability of donor organs has led to the use of
      ventricular assist devices (VADs) to treat heart failure in pediatric patients,
      primarily as bridge to transplantation. How effective VAD therapy is in promoting
      functional recovery in children is currently not known. METHODS: We report
      morbidity and mortality as defined by the Interagency Registry for Mechanically
      Assisted Circulatory Support Modified for Pediatrics (PediMACS) and the use of
      the Treatment Intensity Score to assess functional status for 50 VAD patients
      supported at a single pediatric program from 2004 to 2013. RESULTS: In this
      cohort, 30-day survival on VAD was 98%, and 180-day survival was 83%. Stroke
      occurred in 11 patients (22%), with 8 (16%) resulting in persistent neurologic
      deficit or death. The adverse event rate was 2-fold to 3-fold higher in the first
      7 days of support compared with the subsequent support period. Functional status,
      as measured by the Treatment Intensity Score, improved with duration of support.
      Successful bridge to transplantation was associated with fewer adverse events
      during support and greater improvement in the Treatment Intensity Score during
      the period of support. CONCLUSIONS: Overall survival in this cohort is excellent.
      The risk of serious adverse events decreases over the first month of support.
      However, a clinically significant risk of morbidity and mortality persists for
      the duration of pediatric VAD support. Measures of functional status improve with
      duration of support and are associated with survival to transplantation.

PMID- 26210753
TI  - The risk of PTSD and depression after an airplane crash and its potential
      association with physical injury: A longitudinal study.
AB  - In 2009, a commercial airplane crashed near Amsterdam. This longitudinal study
      aims to investigate (1) the proportion of survivors of the airplane crash showing
      a probable posttraumatic stress disorders (PTSD) or depressive disorder, and (2)
      whether symptoms of PTSD and depression were predicted by trauma characteristics.
      Identifying these trauma characteristics is crucial for early detection and
      treatment. Of the 121 adult survivors, 82 participated in this study 2 months
      after the crash and 76 participated 9 months after the crash. Risk for PTSD and
      depression was measured with the self-report instruments Trauma Screening
      Questionnaire and Patient Health Questionnaire-2. Trauma characteristics assessed
      were Injury Severity Score (ISS), hospitalisation, length of hospital stay, and
      seating position in the plane. Two months after the crash, 32 participants (of
      N=70, 46%) were at risk for PTSD and 28 (of N=80, 32%) were at risk for
      depression. Nine months after the crash, 35 participants (of N=75, 47%) were at
      risk for PTSD and 24 (of N=76, 35%) were at risk for depression. There was a
      moderate correlation between length of hospital stay and symptoms of PTSD and
      depression 9 months after the crash (r=.33 and r=.45, respectively). There were
      no differences in seating position between participants at high risk vs.
      participants at low risk for PTSD or depression. Mixed design ANOVAs showed also
      no association between the course of symptoms of PTSD and depression 2 and 9
      months after the crash and ISS or hospitalisation. This suggests that health care
      providers need to be aware that survivors may be at risk for PTSD or depression,
      regardless of the objective severity of their physical injuries. 

PMID- 26210752
TI  - Long-term safety and efficacy of imatinib in pulmonary arterial hypertension.
AB  - BACKGROUND: Imatinib is an oral inhibitor of several protein kinases implicated
      in the pathophysiology of pulmonary hypertension. Treatment with imatinib
      resulted in improved hemodynamics and exercise capacity in a controlled trial
      (Imatinib [QTI571] in Pulmonary Arterial Hypertension, a Randomized Efficacy
      Study [IMPRES]), among pulmonary arterial hypertension (PAH) patients
      inadequately responsive to 2 to 3 PAH-specific therapies. METHODS: The long-term
      (up to 204 weeks) safety and efficacy of imatinib in this open-label extension
      study were reviewed until early study termination on April 16, 2014. Of 202
      IMPRES-enrolled patients, 66 imatinib and 78 placebo recipients entered the
      extension. RESULTS: Overall, 93.8% (135 of 144) of patients discontinued the
      extension study; administrative issues (i.e., sponsor termination; 32.6%) and
      adverse events (31.3%) were the primary reasons for discontinuation. Nine
      patients completed the extension study before it was terminated. Serious and
      unexpected adverse events were frequent. These included 6 subdural hematomas in
      the extension study and 17 deaths during or within 30 days of study end. Although
      the patients who tolerated imatinib and remained in the extension for a longer
      duration did experience an improvement in functional class and walk distance,
      most discontinued the drug and the study. CONCLUSIONS: Severe adverse events,
      significant side effects, and a high discontinuation rate limit the utility of
      imatinib in the treatment of PAH. These risks outweigh any possible improvements
      in hemodynamics and walk distance seen in those patients able to remain on drug.
      The off-label use of this compound in PAH is discouraged.

PMID- 26210754
TI  - The fate of proximal femoral fractures in the 10th decade of life: an analysis of
      117 consecutive patients.
AB  - INTRODUCTION: To date, there is a lack of valid data with larger populations of
      patients in their 10th decade of life in the analyses of proximal femoral
      fractures. MATERIAL AND METHODS: The inclusion criteria focused on all proximal
      femoral fractures in patients 90-99 years of age who underwent surgical treatment
      between 2009 and 2012. After a period of at least 2 years post-surgery, a
      retrospective collection of empiric data, including the survival time and
      surgical revision rate, was performed. Missing data were collected per telephone
      interview. RESULTS: A total of 121 proximal femoral fractures in 117 patients in
      their 10th decade of life were treated. The mean age was 92.3 years. 61 fractures
      of the femoral neck received hemi- or total hip arthroplasty, while 60
      pertrochanteric or subtrochanteric fractures were treated by osteosynthesis using
      proximal femoral nail (PFN) or dynamic hip screw (DHS). At the time of follow-up,
      83/117 patients (71%) were already deceased. The mortality after 30 days, 6
      months, 1 year and 2 years was 16%, 37%, and 43%, and 55%, respectively. A total
      of 22 surgical revisions (19%) were performed: 10 due to early infections, 8 due
      to haematomas, and 4 due to implant failures with a "cut out" of the femoral neck
      screw exclusively in DHS. The duration of surgery (with regard to surgical
      revision) and ASA classification (with regard to survival rate) were significant
      influence factors. Contralateral proximal femoral fractures were identified in
      24/117 patients (20%), irrespective of study period. CONCLUSIONS: The proximal
      femoral fractures in the 10th decade of life are associated with high
      postoperative mortality within the first 6 months. Surgical revision due to
      complications did not result in a statistically significant reduction of the
      survival time. From the osteosynthetic perspective, the DHS was associated with a
      significantly higher "cut-out" rate compared to PFN procedure. With regard to the
      alloarthoplasty, there were no significant differences observed between hemi- and
      total hip arthroplasty. A contralateral femoral fractures was observed in 20% of
      the total study population, but peri-implant or periprosthetic femoral fractures
      have not been observed in any of the cases thus far.

PMID- 26210755
TI  - Homoarginine, arginine, and relatives: analysis, metabolism, transport,
      physiology, and pathology.
AB  - The year 2008 witnessed the first report on the increase in the concentration of
      L-homoarginine (hArg) in the maternal plasma during human pregnancy. This
      observation, along with a well-known function of hArg, the methylene homologue of
      L-arginine (Arg), as a substrate for nitric oxide (NO) synthase, was the ignition
      for the start of intense research on the physiology and pathology of hArg. The
      circulating concentration of hArg was found to be lower in patients suffering
      from various diseases, and hArg emerged within only very few years as a novel
      cardiovascular risk factor. The compendium in hand comprises original and review
      articles covering several aspects of hArg, Arg and its symmetrically and
      asymmetrically guanidine (N (G))-dimethylated derivatives SDMA and ADMA,
      respectively. In contrast to ADMA and SDMA, low hArg concentrations in plasma or
      serum and in urine are associated with high risks for morbidity and mortality,
      notably in the renal and cardiovascular systems. Acutely and chronically
      administered Arg as a nutritional supplement or in the form of dietary proteins
      is safe in animals and humans and leads to concomitant formation of hArg and
      ADMA, albeit in a different hArg/ADMA ratio. Despite the close but opposite
      associations of hArg and ADMA with disease in adults, children and adolescents,
      the underlying biochemical processes are largely unknown, presumably not
      restricted to NO, and warrant deeper investigation. As the common substrate for
      hArg and ADMA, Arg may play a key role in the biosynthesis and homeostasis of
      hArg and ADMA, two putative antagonists. In animal models of stroke and obesity,
      hArg has beneficial effects. The potential utility of hArg as a therapeutic drug
      or nutritional supplement in humans and animals remains to be elaborated.

PMID- 26210756
TI  - Low-protein diets affect ileal amino acid digestibility and gene expression of
      digestive enzymes in growing and finishing pigs.
AB  - The objective of this study was to evaluate effects of dietary crude protein (CP)
      intake on ileal amino acid digestibilities and expression of genes for digestive
      enzymes in growing and finishing pigs. In Experiment 1, 18 growing pigs (average
      initial BW = 36.5 kg) were assigned randomly into one of three treatments (n =
      6/treatment group) representing normal (18 % CP), low (15 % CP), and very low (12
      % CP) protein intake. In Experiment 2, 18 finishing pigs (average initial BW =
      62.3 kg) were allotted randomly into one of three treatments (n = 6/treatment
      group), representing normal (16 % CP), low (13 % CP) and very low (10 % CP)
      protein intake. In both experiments, diets with low and very low CP were
      supplemented with crystalline amino acids to achieve equal content of
      standardized ileal digestible Lys, Met, Thr, and Trp, and were provided to pigs
      ad libitum. Daily feed intake, BW, and feed/gain ratios were determined. At the
      end of each experiment, all pigs were slaughtered to collect pancreas, small
      intestine samples, and terminal ileal chymes. Samples were used for determining
      expression of genes for digestive enzymes and ileal amino acid digestibilities.
      Growing pigs fed the 12 % CP and 15 % CP diets had lower final body weight (P <
      0.01) and ADG (P < 0.0001) when compared with pigs fed the 18 % dietary CP diet.
      Growing pigs fed with the 12 % CP diet showed higher digestibilities for CP (P <
      0.05), DM (P < 0.05), Lys (P < 0.0001), Met (P < 0.01), Cys (P < 0.01), Thr (P <
      0.01), Trp (P < 0.05), Val (P < 0.05), Phe (P < 0.05), Ala (P < 0.05), Cys (P <
      0.01), and Gly (P < 0.05) than those fed the 18 % CP diet. Finishing pigs fed the
      16 % CP diet had a higher (P < 0.01) final body weight than those fed the 10 % CP
      diet. mRNA levels for digestive enzymes (trypsinogen, chymotrypsin B, and
      dipeptidases-II and III) differed among the three groups of pigs (P < 0.05), and
      no difference was noted in the genes expression between control group and lower
      CP group. These results indicated that a reduction of dietary CP by a six
      percentage value limited the growth performance of growing-finishing pigs and
      that a low-protein diet supplemented with deficient amino acids could reduce the
      excretion of nitrogen into the environment without affecting weight gain.

PMID- 26210757
TI  - The female urinary microbiome in urgency urinary incontinence.
AB  - OBJECTIVE: The purpose of this study was to characterize the urinary microbiota
      in women who are planning treatment for urgency urinary incontinence and to
      describe clinical associations with urinary symptoms, urinary tract infection,
      and treatment outcomes. STUDY DESIGN: Catheterized urine samples were collected
      from multisite randomized trial participants who had no clinical evidence of
      urinary tract infection; 16S ribosomal RNA gene sequencing was used to
      dichotomize participants as either DNA sequence-positive or sequence-negative.
      Associations with demographics, urinary symptoms, urinary tract infection risk,
      and treatment outcomes were determined. In sequence-positive samples, microbiotas
      were characterized on the basis of their dominant microorganisms. RESULTS: More
      than one-half (51.1%; 93/182) of the participants' urine samples were sequence
      positive. Sequence-positive participants were younger (55.8 vs 61.3 years old; P
      = .0007), had a higher body mass index (33.7 vs 30.1 kg/m(2); P = .0009), had a
      higher mean baseline daily urgency urinary incontinence episodes (5.7 vs 4.2
      episodes; P < .0001), responded better to treatment (decrease in urgency urinary
      incontinence episodes, -4.4 vs -3.3; P = .0013), and were less likely to
      experience urinary tract infection (9% vs 27%; P = .0011). In sequence-positive
      samples, 8 major bacterial clusters were identified; 7 clusters were dominated
      not only by a single genus, most commonly Lactobacillus (45%) or Gardnerella
      (17%), but also by other taxa (25%). The remaining cluster had no dominant genus
      (13%). CONCLUSION: DNA sequencing confirmed urinary bacterial DNA in many women
      with urgency urinary incontinence who had no signs of infection. Sequence status
      was associated with baseline urgency urinary incontinence episodes, treatment
      response, and posttreatment urinary tract infection risk.

PMID- 26210759
TI  - Experimental development of a new protocol for extraction and characterization of
      microplastics in fish tissues: First observations in commercial species from
      Adriatic Sea.
AB  - The presence of microplastics in the marine environment has raised scientific
      interest during the last decade. Several organisms can ingest microplastics with
      potentially adverse effects on the digestive tract, respiratory system and
      locomotory appendages. However, a clear evidence of tissue accumulation and
      transfer of such microparticles in wild organisms is still lacking, partially
      hampered by technical difficulties in isolation and characterization protocols
      from biological samples. In this work, we compared the efficacy of some existing
      approaches and we optimized a new protocol allowing an extraction yield of
      microplastics from fish tissues ranging between 78% and 98%, depending on the
      polymer size. FT-IR analyses confirmed that the extraction procedure did not
      affect the particles characteristics. The method was further validated on the
      fish mullet, Mugil cephalus, exposed under laboratory conditions to polystyrene
      and polyethylene; the particles were isolated and quantified in stomach and
      liver, and their presence in the hepatic tissue was confirmed also by
      histological analyses. A preliminary characterization revealed the presence and
      distribution of microplastics in various fish species collected along the
      Adriatic Sea. FT-IR analyses indicated polyethylene as the predominant polymer
      (65%) in the stomach of fish. The overall results confirmed the newly developed
      method as a reliable approach to detect and quantify microplastics in the marine
      biota. 

PMID- 26210758
TI  - Population-level trends in relative survival for cervical cancer.
AB  - OBJECTIVE: While the last 3 decades have seen numerous advances in the treatment
      of cervical cancer, it remains unclear if population-level survival has improved.
      We examined relative survival, the ratio of survival in cervical cancer patients
      to matched controls over time. STUDY DESIGN: Patients with cervical cancer
      diagnosed from 1983 through 2009 and recorded in the Surveillance, Epidemiology,
      and End Results database were examined. Survival models were adjusted for age,
      race, stage, year of diagnosis, and time since diagnosis. Changes in stage
      specific relative survival for patients with cervical cancer compared to the
      general population matched by age, race, and calendar year were examined over
      time. RESULTS: A total of 46,932 patients were identified. For women with stage I
      tumors, the excess hazard ratio for women diagnosed in 2009 was 0.91 (95%
      confidence interval [CI], 0.86-0.95) compared to 2000, 0.81 (95% CI, 0.73-0.91)
      compared to 1990, and 0.75 (95% CI, 0.64-0.88) compared to 1983. For patients
      with stage III tumors, the excess hazard ratios for patients diagnosed in 2009
      (relative to those diagnosed in 2000, 1990, and 1983) were 0.83 (95% CI, 0.80
      0.87), 0.68 (95% CI, 0.62-0.75), and 0.59 (95% CI, 0.52-0.68). Similar trends in
      improved survival over time were noted for women with stage II tumors. There were
      no statistically significant improvements in relative survival over time for
      women with stage IV tumors. CONCLUSION: Relative survival has improved over time
      for women with stage I-III cervical cancer, but has changed little for those with
      metastatic disease.

PMID- 26210760
TI  - Preseptal cellulitis caused by Neisseria gonorrhoeae: A rare disease need to be
      vigilant.

PMID- 26210761
TI  - Investigation of mechanisms and molecular epidemiology of linezolid
      nonsusceptible Enterococcus faecalis isolated from a teaching hospital in China.
AB  - The epidemiological and molecular characteristics of eight linezolid
      nonsusceptible Enterococcus faecalis isolated from a teaching hospital in China
      (January to July 2014) were investigated. The target site modifications and cfr
      gene associated with linezolid resistance were not found. Results of the
      epidemiological investigation indicated that linezolid resistance possibly
      occurred on several independent occasions and was often not related to linezolid
      administration. 

PMID- 26210762
TI  - Mammographic detection of breast arterial calcification as an independent
      predictor of coronary atherosclerotic disease in a single ethnic cohort of
      African American women.
AB  - OBJECTIVE: Accumulating data on predominantly Caucasian women suggests an
      association between breast arterial calcification (BAC) and coronary artery
      disease (CAD). We sought to comprehensively examine the correlation between
      mammographic BAC and CAD endpoints detected by cardiac computed tomography (CCT)
      in African American (AA) women. METHODS: Consecutive AA women who underwent
      digital screening mammography and CCT were identified. In blinded fashion,
      mammographic and CCT studies were reviewed. Patient-related pertinent covariates
      were assessed. RESULTS: Two-hundred-four AA women (median age, 52.5 years) were
      included. BAC was present in 42 women (20.6%). BAC was significantly associated
      with coronary artery calcium score >100 (odds ratio [OR], 7.66; 95% confidence
      interval [CI], 2.75-21.29; P < 0.001), atherosclerotic luminal narrowing (OR,
      9.99; CI, 3.65-27.32; P < 0.001), and stenosis >=50% (OR, 5.48; CI, 1.97-15.23; P
      = 0.001) by CCT. CONCLUSION: In AA women, BAC is associated with increased
      probability of coronary calcification, atherosclerosis, and CAD on CCT.

PMID- 26210763
TI  - Using Feedlot Operational Data to Make Valid Conclusions for Improving Health
      Management.
AB  - Feedlot operational data can be useful for monitoring cattle health and
      performance outcomes and evaluating associations between these outcomes and
      potentially important cattle population or management factors. Operational data
      are inherently relevant to clients; however, there are potential limitations that
      need to be considered to make appropriate conclusions. Assessing data quality,
      potential for bias, data distributions, and multiple health outcomes can provide
      a more thorough understanding of feedlot cattle health and factors that may
      affect health management systems. Accurate and useful information is derived only
      when the advantages and limitations of the data and the analysis process are
      fully understood. 

PMID- 26210764
TI  - A Systematic Review of Bovine Respiratory Disease Diagnosis Focused on Diagnostic
      Confirmation, Early Detection, and Prediction of Unfavorable Outcomes in Feedlot
      Cattle.
AB  - A large proportion of newly arrived feedlot cattle are affected with bovine
      respiratory disease (BRD). Economic losses could be reduced by accurate, early
      detection. This review evaluates the available literature regarding BRD
      confirmatory diagnostic tests, early detection methods, and modalities to
      estimate post-therapeutic prognosis or predict unfavorable or fatal outcomes.
      Scientific evidence promotes the use of haptoglobin to confirm BRD status.
      Feeding behavior, infrared thermography, and reticulorumen boluses are promising
      methods. Retrospective analyses of routinely collected treatment and cohort data
      can be used to identify cattle at risk of unfavorable outcome. Other methods have
      been reviewed but require further study. 

PMID- 26210765
TI  - Bovine Viral Diarrhea Virus-Associated Disease in Feedlot Cattle.
AB  - Bovine viral diarrhea virus (BVDv) is associated with bovine respiratory disease
      complex and other diseases of feedlot cattle. Although occasionally a primary
      pathogen, BVDv's impact on cattle health is through the immunosuppressive effects
      of the virus and its synergism with other pathogens. The simple presence or
      absence of BVDv does not result in consistent health outcomes because BVDv is
      only one of many risk factors that contribute to disease syndromes. Current
      interventions have limitations and the optimum strategy for their uses to limit
      the health, production, and economic costs associated with BVDv have to be
      carefully considered for optimum cost-effectiveness. 

PMID- 26210766
TI  - Management of Feedyard Hospitals.
AB  - There are many considerations when managing feedyard hospitals. The type of
      hospital system must fit the facility design, the type of cattle fed at the
      feedyard, the crew that is employed by the feedyard, and the protocol established
      by the veterinarian. Ensuring the animals are well-cared for and have their basic
      needs met should be the priority of the feedyard personnel and the veterinarian
      maintaining the veterinarian-client-patient relationship with the feedyard. 

PMID- 26210767
TI  - Surgical Management of Orthopedic and Musculoskeletal Diseases of Feedlot Calves.
AB  - Injuries, infections, and disorders of the musculoskeletal system are common in
      feedlot calves. These conditions often are amenable to surgical treatment with
      return of the calf to productivity. Weight gain and carcass quality are expected
      to be significantly adversely affected by pain and debilitation. The goal of
      surgical management of disorders of the joints, muscles, and feet should be
      resolution of the inciting cause, mitigation of pain, and restoration of form and
      function. If these are achieved, calves should return to acceptable, if not
      normal, feed intake, rate of gain, and carcass quality. 

PMID- 26210768
TI  - Surgical Management of Common Disorders of Feedlot Calves.
AB  - Procedures to improve animal and handler safety, shape production parameters, and
      directly address the prosperity of individuals in need of assistance are
      performed routinely. Techniques to accomplish these tasks have been described in
      many venues. Painful procedures are expected in feedlot practice. Assessing and
      managing pain and welfare for these procedures has strengthened significantly
      over the past decade to address increased public concerns and also to support the
      desires of the operators/managers to progress. Methods to perform common
      procedures are described, including evidence and techniques for managing the pain
      and distress while performing them. 

PMID- 26210769
TI  - Investigating Outbreaks of Disease or Impaired Productivity in Feedlot Cattle.
AB  - Most cattle move through cattle feeding and finishing systems without health
      problems or impairment of productivity, but some cattle do become ill or
      unproductive. When cattle get sick, understanding what has gone wrong and how to
      remedy the situation is important. An orderly, systematic approach to
      investigating disease outbreaks is more likely to lead to a solution. The
      solution may come from identifying and modifying human decisions or behaviors
      that may be far removed in time or place from the immediate problem.
      Veterinarians can help cattle feeders recognize and correct the system dynamics
      factors affecting cattle health and performance. 

PMID- 26210770
TI  - Optimizing Feedlot Diagnostic Testing Strategies Using Test Characteristics,
      Disease Prevalence, and Relative Costs of Misdiagnosis.
AB  - Diagnostic tests are commonly used by feedlot practitioners and range from
      clinical observations to more advanced physiologic testing. Diagnostic
      sensitivity and specificity, estimated prevalence in the population, and the
      costs of misdiagnoses need to be considered when selecting a diagnostic test
      strategy and interpreting results. This article describes methods for evaluating
      diagnostic strategies using economic outcomes to evaluate the most appropriate
      strategy for the expected situation. The diagnostic sensitivity and specificity,
      and expected prevalence influence the likelihood of misdiagnosis in a given
      population, and the estimated direct economic impact can be used to quantify
      differences among diagnostic strategies. 

PMID- 26210771
TI  - Frequency and covariates of fear of death during myocardial infarction and its
      impact on prehospital delay: findings from the multicentre MEDEA Study.
AB  - BACKGROUND: Fear of death (FoD) is an exceptionally stressful symptom of ST
      elevation myocardial infarction (STEMI), which received little scientific
      attention in recent years. We aimed to describe the prevalence and factors
      contributing to FoD among STEMI patients and assess the impact of FoD on
      prehospital delay. METHODS: This investigation was based on 592 STEMI patients
      who participated in the Munich Examination of Delay in Patients Experiencing
      Acute Myocardial Infarction (MEDEA) study. Data on sociodemographic, clinical and
      psycho-behavioral characteristics were collected at bedside. Multivariate
      logistic regression models were used to identify factors associated with FoD.
      RESULTS: A total of 15% of STEMI patients reported FoD (n = 88), no significant
      gender difference was found. STEMI pain strength [OR = 2.3 (1.4-3.9)], STEMI
      symptom severity [OR = 3.7 (2-6.8)], risk perception pre-STEMI [OR = 1.9 (1.2
      3.2)] and negative affectivity [OR = 1.9 (1.2-3.1)] were independently associated
      with FoD. The median delay for those who experienced FoD was 139 min compared to
      218 min for those who did not (p = 0.005). Male patients with FoD were
      significantly more likely to delay less than 120 min [OR = 2.11(1.25-3.57); p =
      0.005], whereas in women, this association was not significant. Additionally, a
      clear dose-response relationship between fear severity and delay was observed.
      Male FoD patients significantly more often used emergency services to reach the
      hospital (p = 0.003). CONCLUSIONS: FoD is experienced by a clinically meaningful
      minority of vulnerable STEMI patients and is strongly associated with shorter
      delay times in men but not in women. Patients' uses of emergency services play an
      important role in reducing the delay in male FoD patients.

PMID- 26210772
TI  - Physical activity, symptoms, medication and subjective health among veteran
      endurance athletes with atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is highly prevalent, but has not previously
      been characterized in detail in veteran athletes. We aimed to describe physical
      activity (PA), symptoms, medication and subjective health in relation to AF
      subtype and co-morbidity among veteran cross-country skiers with AF. METHODS: In
      total, 4952 Norwegian men and women aged 53-85 years took part in this cohort
      study, 2626 veteran cross-country skiers and 2326 from the general population.
      PA, endurance exercise, functional capacity, co-morbidity, drug use and
      subjective health were self-reported by questionnaires. AF was self-reported and
      confirmed by electrocardiograms in a medical record review. RESULTS: The
      prevalence of self-reported AF among veteran skiers was 12.3%. AF was confirmed
      in 140 skiers and 118 individuals from the general population. Among skiers with
      AF (mean age 69 years), 52% had paroxysmal, 23% persistent and 24% permanent AF.
      AF was associated with poor subjective health, but 89% of the veteran skiers were
      physically active and 64% engaged in regular endurance exercise after the onset
      of AF. While 59% had experienced palpitations during the past year, 32% reported
      reduced functional capacity. Two out of three with AF and a CHA2DS2-VASc score >=
      2 used oral anticoagulants (OACs). CONCLUSIONS: AF was associated with poor
      subjective health, but the vast majority of veteran athletes engaged in regular
      PA and endurance exercise also after the onset of AF. This is important, as PA
      and exercise might reduce AF symptoms, mortality and morbidity. Many veteran
      skiers with AF were not optimally treated with OACs.

PMID- 26210773
TI  - The presentation of Legg-Calve-Perthes disease in females.
AB  - PURPOSE: Legg-Calve-Perthes disease (LCPD) is uncommon in girls. The presentation
      of LCPD in female patients has been reported as later in onset and associated
      with certain high-impact activities. Our aim is to characterize the presentation
      of female LCPD at a large center, with particular attention to the clinical and
      radiographic features of late-onset disease (>ten years of age). We perceived an
      increasing burden of late-onset disease with adult-like radiographic features.
      METHODS: All patients presenting to a single large urban children's hospital from
      1990-2014 with a diagnosis of LCPD were reviewed. Demographic, clinical, and
      radiographic data for all female patients were examined and compared to
      historical norms. RESULTS: Four-hundred and fifty-one patients presented with
      LCPD in the study period, of which 82 (18.2 %) were female. The average age at
      presentation was 6.58 years in girls, which is similar to the classically
      reported mean age. Fourteen patients participated in high-impact repetitive
      activities or those with deep flexion and abduction, although few were late
      presenters. There were four female patients who presented for initial diagnosis
      >ten years of age. CONCLUSIONS: There was a paucity of late-onset LCPD in girls
      in the study population, and the females with LCPD had a very similar age and
      character to their presentation as did males. Although their presentation is
      infrequent, three of four older females with LCPD were engaged in high-level
      physical activity, and their disease may be attributed to high-impact, repetitive
      athletics. LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 26210774
TI  - Adjusting export tax rebates to reduce the environmental impacts of trade:
      Lessons from China.
AB  - Export tax rebates are an important policy instrument for stimulating exports,
      which many developing countries make use of. However, excessive export tax
      rebates and inappropriate structural arrangements can lead to over-production in
      highly polluting industries and cause the environment to deteriorate. This paper,
      taking China as the study case, tests and verifies the statistical significance
      of the causal relationship between export tax rebates and pollution emissions.
      With a computable general equilibrium modeling, the current study further
      analyzes the effectiveness of export tax rebate adjustments aimed at alleviating
      environmental pressure for different time periods. It is found that before 2003,
      export tax rebates primarily promoted exports and boosted foreign exchange
      reserves, and highly polluting sectors enjoyed above-average export tax rebates,
      which led to increased pollution emissions. Between 2003 and 2010, the export tax
      rebate system was reformed to reduce support for the highly polluting export
      sectors, which led to decreases in emissions. Canceling export tax rebates for
      highly polluting sectors is shown to be the most favorable policy choice for
      improving the environmental performance of China's international trade. This
      study can serve as reference for other developing countries which similarly rely
      on export tax rebates, so that they can adjust their policies so as to combine
      economic growth with pollution control. 

PMID- 26210775
TI  - Reviewing public policy for promoting population oral health in Victoria,
      Australia (2007-12).
AB  - OBJECTIVE: Government policy and planning set the direction for community
      decisions related to resource allocation, infrastructure, services, programs,
      workforce and social environments. The aim ofthe present study was to examine the
      policy and planning context for oral health promotion in Victoria, Australia,
      over the period 2007-12. METHODS: Key Victorian policies and plans related to
      oral health promotion in place during the 2007-12 planning cycle were identified
      through online searching, and content analysis was performed. Inclusion of oral
      health (and oral health-related) promotion initiatives was assessed within the
      goals, objectives and strategies sections of each plan. RESULTS: Six of the 223
      public health plans analysed (3%) included oral health 'goals' (including one
      plan representing nine agencies). Oral health was an 'objective' in 10 documents.
      Fifty-six plan objectives, and 70 plan strategies related to oral health or
      healthy eating for young children. Oral health was included in municipal plans
      (44%) more frequently than the other plans examined. CONCLUSION: There is a
      policy opportunity to address oral health at a community level, and to implement
      population approaches aligned with the Ottawa Charter that address the social
      determinants of health.

PMID- 26210776
TI  - How demography-driven evolving networks impact epidemic transmission between
      communities.
AB  - In this paper, we develop a complex network susceptible-infected-susceptible
      (SIS) model to investigate the impact of demographic factors on disease spreads.
      We carefully capture the transmission by short-time travelers, by assuming the
      susceptibles randomly travel to another community, stay for a daily time scale,
      and return. We calculate the basic reproductive number R0 and analyze the
      relevant stability of the equilibria (disease-free equilibrium and endemic
      equilibrium) of the model by applying limiting system theory and comparison
      principle. The results reveal that the disease-free equilibrium is globally
      asymptotically stable given R0<1, whereas the condition R0>1 leads to a globally
      asymptotically stable endemic equilibrium. Our numerical simulations show that
      demographic factors, such as birth, immigration, and short-time travels, play
      important roles in epidemic propagation from one community to another. Moreover,
      we quantitatively demonstrate how the distribution of individual's network degree
      would affect the result of disease transmission.

PMID- 26210777
TI  - Methionine sulfoxide reductase A deficiency exacerbates progression of kidney
      fibrosis induced by unilateral ureteral obstruction.
AB  - Methionine sulfoxide reductase A (MsrA), which stereospecifically catalyzes the
      reduction of methionine-S-sulfoxide, is an important reactive oxygen species
      (ROS) scavenger. Tissue fibrosis is a maladaptive repair process following
      injury, associated with oxidative stress. In this study, we investigated the role
      of MsrA in unilateral ureteral obstruction (UUO)-induced kidney fibrosis and its
      underlying mechanisms by using MsrA gene-deleted mice (MsrA(-/-)). MsrA deletion
      increased collagen deposition in the interstitium and the expression of collagen
      III and alpha-smooth muscle actin in the UUO kidneys, indicating that MsrA
      deficiency exacerbated the progression of UUO-induced kidney fibrosis. UUO
      reduced the kidney expression of MsrA, MsrB1, and MsrB2, thereby decreasing MsrA
      and MsrB activity. UUO increased hydrogen peroxide and lipid peroxidation levels
      and the ratio of oxidized glutathione (GSSG) to total glutathione (GSH) in the
      kidneys. The UUO-induced elevations in the levels of these oxidative stress
      markers and leukocyte markers were much higher in the MsrA(-/-) than in the
      MsrA(+/+) kidneys, the latter suggesting that the exacerbated kidney fibrosis in
      MsrA(-/-) mice was associated with enhanced inflammatory responses. Collectively,
      our data suggest that MsrA plays a protective role in the progression of UUO
      induced kidney fibrosis via suppression of fibrotic responses caused by oxidative
      stress and inflammation. 

PMID- 26210778
TI  - Outcome of neoadjuvant chemotherapy in BRCA1/2 mutation positive women with
      advanced-stage Mullerian cancer.
AB  - OBJECTIVES: To investigate whether patients with germline BRCA1/2 mutations who
      received neoadjuvant chemotherapy (NAC) for advanced-stage Mullerian cancer (MC)
      have an improved outcome compared to patients who did not undergo genetic
      testing. METHODS: Three hundred and two patients who received NAC for stage III
      IV MC were identified from a multi-institutional study involving Cleveland Clinic
      and Brigham and Women's Hospital for 2000-2014 and 2010-2014 respectively.
      Patients were divided into 3 cohorts: patients with germline BRCA1/2 mutations
      (BRCA_mut+; N=30), patients with no genetic testing (BRCA_mut_unk; N=166) and
      patients with negative genetic testing (BRCA_mut-, N=106). RESULTS: There were no
      differences in the clinical characteristics and rates of complete cytoreduction
      and bowel resection between the three groups. BRCA_mut+ had longer PFS compared
      to BRCA_mut_unk and BRCA_mut- (19.1 vs. 15.1 vs. 15.7months respectively.
      However, this difference was not statistically significant (p=0.48). Patients
      with BRCA2 mutation had non-significant trend toward longer PFS compared to
      patients with unknown BRCA or BRCA1 mutation (20.2 vs. 15.1 vs. 14.8months
      respectively, p=0.58). BRCA_mut+ and BRCA_mut- had longer overall survivals (OS)
      compared to BRCA_mut_unk patients (50.5 vs. 54.1 vs. 36.5months respectively,
      p=0.009). In multivariable analyses, controlling for age, stage and complete
      cytoreduction, BRCA_mut_unk was associated with worse PFS (HR 1.44, 95% CI 1.01
      2.05, p=0.045) and OS (HR 2.67, 95% CI 1.33-5.36, p=0.006). CONCLUSIONS: Patients
      with germline BRCA mutations had improved outcomes with NAC compared to patients
      with unknown BRCA status. These outcomes were more favorable compared to the
      outcome of NAC in prior studies.

PMID- 26210779
TI  - An integrated CAD/CAM/robotic milling method for custom cementless femoral
      prostheses.
AB  - Aseptic loosening is the primary cause of cementless femoral prosthesis failure
      and is related to the primary stability of the cementless femoral prosthesis in
      the femoral cavity. The primary stability affects both the osseointegration and
      the long-term stability of cementless femoral prostheses. A custom cementless
      femoral prosthesis can improve the fit and fill of the prosthesis in the femoral
      cavity and decrease the micromotion of the proximal prosthesis such that the
      primary stability of the custom prosthesis can be improved, and osseointegration
      of the proximal prosthesis is achieved. These results will help to achieve long
      term stability in total hip arthroplasty (THA). In this paper, we introduce an
      integrated CAD/CAM/robotic method of milling custom cementless femoral
      prostheses. The 3D reconstruction model uses femoral CT images and 3D design
      software to design a CAD model of the custom prosthesis. After the transformation
      matrices between two units of the robotic system are calibrated, consistency
      between the CAM software and the robotic system can be achieved, and errors in
      the robotic milling can be limited. According to the CAD model of the custom
      prosthesis, the positions of the robotic tool points are produced by the CAM
      software of the CNC machine. The normal vector of the three adjacent robotic tool
      point positions determines the pose of the robotic tool point. In conclusion, the
      fit rate of custom pig femur stems in the femoral cavities was 90.84%. After
      custom femoral prostheses were inserted into the femoral cavities, the maximum
      gaps between the prostheses and the cavities measured less than 1 mm at the
      diaphysis and 1.3 mm at the metaphysis.

PMID- 26210781
TI  - Post-partum Residential Mobility Among a Statewide Representative Sample of
      California Women, 2003-2007.
AB  - OBJECTIVES: Researchers often examine neighborhood socioeconomic environment and
      health during the perinatal period using geocoded addresses recorded on birth
      certificates at the time of delivery. Our objective was to assess the potential
      for post-partum neighborhood misclassification by examining whether women move
      neighborhoods during the immediate post-partum period, whether they move to
      neighborhoods of different socioeconomic status (SES), and whether mobility
      differs by maternal characteristics. METHODS: We used data from the 2003-2007
      California Maternal and Infant Health Assessment (MIHA), an annual, statewide
      representative survey of post-partum women, to examine women's neighborhood
      mobility patterns between giving birth and completing a survey 2-7 months post
      partum. We examined whether women changed neighborhoods, whether moves were to
      neighborhoods of higher, lower, or similar socioeconomic status (SES), and
      whether these patterns differed by maternal race/ethnicity, maternal SES, or
      other demographic characteristics. RESULTS: Overall, 93% of women either did not
      move neighborhoods or moved to a neighborhood of similar SES post-partum. Only 4%
      of women moved to a neighborhood of lower SES and 3% to an area of higher SES.
      Mothers who were non-Hispanic black or US-born Hispanic, young, unmarried,
      primiparous, or lower SES were slightly more likely to move overall and more
      likely to move to neighborhoods with different SES, compared to other women.
      CONCLUSIONS: These findings suggest that geocoded addresses from birth
      certificates can be used to estimate women's neighborhood SES during the early
      post-partum period with little misclassification, an especially relevant finding
      for researchers using post-partum surveys.

PMID- 26210780
TI  - Health and Safety Checklist for Early Care and Education Programs to Assess Key
      National Health and Safety Standards.
AB  - OBJECTIVES: The project aims were to (1) develop an observational Health and
      Safety Checklist to assess health and safety practices and conditions in early
      care and education (ECE) programs using Stepping Stones To Caring For Our
      Children, 3rd Edition national standards, (2) pilot test the Checklist, completed
      by nurse child care health consultants, to assess feasibility, ease of
      completion, objectivity, validity, and reliability, and (3) revise the Checklist
      based on the qualitative and quantitative results of the pilot study. METHODS:
      The observable national health and safety standards were identified and then
      rated by health, safety, and child care experts using a Delphi technique to
      validate the standards as essential to prevent harm and promote health. Then,
      child care health consultants recruited ECE centers and pilot tested the 124-item
      Checklist. The pilot study was conducted in Arizona, California and North
      Carolina. The psychometric properties of the Checklist were assessed. RESULTS:
      The 37 participating ECE centers had 2627 children from ethnically-diverse
      backgrounds and primarily low-income families. The child care health consultants
      found the Checklist easy to complete, objective, and useful for planning health
      and safety interventions. The Checklist had content and face validity, inter
      rater reliability, internal consistency, and concurrent validity. Based on the
      child care health consultant feedback and psychometric properties of the
      Checklist, the Checklist was revised and re-written at an 8th grade literacy
      level. CONCLUSION: The Health and Safety Checklist provides a standardized
      instrument of observable, selected national standards to assess the quality of
      health and safety in ECE centers.

PMID- 26210782
TI  - Survival in systemic sclerosis-pulmonary arterial hypertension by serum
      autoantibody status in the Pulmonary Hypertension Assessment and Recognition of
      Outcomes in Scleroderma (PHAROS) Registry.
AB  - OBJECTIVE: To determine the association between serum autoantibodies and survival
      in patients with incident systemic sclerosis (SSc)-pulmonary arterial
      hypertension (PAH) enrolled in the Pulmonary Hypertension Assessment and
      Recognition of Outcomes in Scleroderma (PHAROS) Registry. METHODS: Patients with
      definite PAH diagnosed by right heart catheterization within 6 months of registry
      enrollment were studied. Serum autoantibodies were assayed at each participating
      institution's clinical laboratory. Mortality data were collected from electronic
      medical records and/or the Social Security Death Index. Kaplan-Meier survival
      estimates were reported for five autoantibody groups (anticentromere/AC,
      nucleolar ANA/NUC, anti-topoisomerase/Scl-70, overlapping or non-specific
      autoantibodies/other, and a combined group with similar survival consisting of
      RNA polymerase III, U1RNP, and autoantibody-negative patients). Cox proportional
      hazards models permitted examination of the association between autoantibody
      groups and overall survival, controlling for age, sex, race, and SSc disease
      duration. RESULTS: In all, 162 subjects had PAH, and serum autoantibody and
      survival information; 60 (37%) had AC, 39 (24%) NUC, 11 (7%) Scl-70, 28 (17%) had
      other, 9 (6%) RNA pol, 8 (5%) U1RNP autoantibodies, and 7 (4%) had negative
      antibodies; 32 (20%) subjects died over a median follow-up time of 2.1 years
      (range: 0.01-6.8); 1- and 3-year survival estimates were, respectively, 94% and
      78% for AC, 94% and 72% for NUC, 89% and 63% for Scl-70, 92% and 79% for the
      other group, and 100% and 93% for the combined group. Unadjusted and adjusted
      hazard ratios revealed no statistically significant association between risk of
      death and autoantibodies. CONCLUSION: Anticentromere and NUC autoantibodies are
      prevalent in SSc-PAH patients. An association between serum autoantibodies and
      survival in patients with SSc-PAH was not identified in the PHAROS cohort.

PMID- 26210784
TI  - Signal of Interest Selection Standard for Ultrasonic Backscatter in Cancellous
      Bone Evaluation.
AB  - The aim of this study was to examine the effect of the backscattered signal of
      interest (SOI) on ultrasonic cancellous bone evaluation. In vitro backscatter
      measurements were performed using 16 bovine cancellous bone specimens and six
      different transducers with central frequencies of 0.5, 1, 2.25, 3.5, 5 and 10
      MHz. The SOI for signal analysis was selected by a rectangular window. The delay
      (T1) and duration (T2) of the time window were varied, and the apparent
      integrated backscatter (AIB) and its correlation to bone volume fraction (BV/TV)
      were calculated. The results indicate that in addition to affecting the measured
      value of AIB, the SOI influences the observed correlation between AIB and BV/TV.
      Strong positive correlations were observed for short T1 (0.5 MHz: <=6 MUs, 1 MHz:
      <=3 MUs, 2.25 and 3.5 MHz: <=2 MUs, 5 and 10 MHz: <=1 MUs). However, strong
      negative correlations were observed when T1 was long (0.5 MHz: >9 MUs, 1 MHz: >7
      MUs, 2.25 and 3.5 MHz: >3 MUs, 5 and 10 MHz: >2 MUs). The T2 value, especially
      low values (<=3 MUs), also influenced the correlation coefficients. Positive
      correlations were more commonly observed at lower frequencies (i.e., 0.5-1 MHz),
      whereas negative correlations were more common at higher frequencies (i.e., 2.25
      10 MHz). An explicit standard for in vitro SOI selection and cancellous bone
      assessment was proposed for a broad frequency range (0.5-10 MHz). Current
      conflicting findings are explained, and constructive suggestions for ultrasonic
      backscatter cancellous bone evaluation are provided.

PMID- 26210783
TI  - Pregnancy outcomes following exposure to abatacept during pregnancy.
AB  - OBJECTIVE: To characterize pregnancy outcomes following maternal and paternal
      exposure to abatacept, using clinical trial and post-marketing data available to
      the manufacturer. METHODS: All confirmed cases of pregnancy with outcome data
      reported to the manufacturer up to September 1, 2014 were included. Sources
      included clinical trials, spontaneously reported (unsolicited) post-marketing
      cases, and the Organization of Teratology Information Specialists registry.
      Details recorded included number of live births, spontaneous abortions and
      terminations, pregnancy complications, and congenital anomalies. RESULTS: A total
      of 161 pregnancies with known outcomes were identified between 1995 and September
      2014: 151 were following maternal exposure to abatacept and 10 were following
      paternal exposure. Seven of 86 (8.1%) live births following maternal exposure had
      congenital anomalies (cleft lip/cleft palate, congenital aortic anomaly,
      meningocele, pyloric stenosis, skull malformation, ventricular septal
      defect/congenital arterial malformation, and Down's syndrome with premature
      rupture of membranes at 17 weeks that resulted in a live birth via cesarean
      section and subsequent infant death). In addition, 59 of the 151 (39.0%) cases
      with maternal exposure resulted in abortions (40 spontaneous and 19 elective). Of
      the 10 pregnancies with paternal exposure, there were nine live births and one
      elective abortion, with no congenital abnormalities identified and no fetal
      deaths. CONCLUSIONS: Based on these data, there does not appear to be a pattern
      of congenital anomalies following maternal or paternal exposure to abatacept. No
      cases of vertebral defects, anal atresia, cardiac defects, tracheo-esophageal
      fistula, renal anomalies, or limb abnormalities (VACTERL) were noted. Spontaneous
      abortion rates were within expected range. Abatacept should be used during
      pregnancy only if the potential benefit to the mother justifies the potential
      risk to the fetus.

PMID- 26210786
TI  - Effect of Linker Flexibility on the Catalytic Features of a Glycoside Hydrolase
      Family 45 Endoglucanase from Rhizopus stolonifer.
AB  - This study investigated an endoglucanase (EGII) from Rhizopus stolonifer var.
      reflexus TP-02 that consists of a C-terminal catalytic domain and an N-terminal
      carbohydrate-binding module joined by a linker rich in glycine, serine,
      threonine, and alanine. Site-directed mutagenesis was applied to characterize the
      conformation and dynamics of the linker. Mutants were expressed in Escherichia
      coli BL21 and purified by Ni-chelating column. Structural analysis indicated that
      glycine provided flexibility in the enzymatic process. G67P, G91Y, G101Y, G108Y,
      G109Y, G112P, H61G, H75G, and Y103G were selected on the basis of the results of
      the bioinformatics and Ramachandran plot analysis for the linker. The catalytic
      activities of EGII and its mutants on CMC-Na, microcrystalline cellulose
      (Avicel), and phosphoric acid-swollen celluloses (PASC) showed that flexible
      amino acids strengthened the activity of the enzyme. It indicated that flexible
      amino acids could improve the flexibility of the linker. Overall, the linker
      affected the catalytic efficiency of the endoglucanase in hydrolyzing cellulose
      chains. 

PMID- 26210785
TI  - Quantitative Contrast-Enhanced Ultrasonic Imaging Reflects Microvascularization
      in Hepatocellular Carcinoma and Prognosis after Resection.
AB  - Our aim was to evaluate the correlation between tumor vasculature detected by pre
      surgical contrast-enhanced ultrasonography and the post-surgical prognosis of
      patients with hepatocellular carcinoma. One hundred ninety-five patients with
      hepatocellular carcinoma who had undergone curative resection and pre-operative
      contrast-enhanced ultrasonography were enrolled. Intra-tumoral microvessels were
      evaluated by immunohistochemical staining for anti-CD31 and anti-CD34. On the
      basis of the immunohistochemical staining and morphology patterns, tumors were
      divided into capillary-like and sinusoid-like microvessel subtypes. The rise time
      of tumors was shorter in the capillary-like microvessel subtype than in the
      sinusoid-like microvasculature subtype (p = 0.026). Intra-tumor microvascular
      density (p < 0.001, hazard ratio = 0.137) and rise time (p = 0.006, hazard ratio
      = 2.475) were independent factors corresponding to different microvasculature
      types. Microvascular density, vascular invasion and wash-in perfusion index were
      determined to be independent factors in recurrence-free survival and overall
      survival. In conclusion, contrast-enhanced ultrasonography may serve as a means
      of non-invasive assessment of tumor angiogenesis and may be associated with the
      survival of patients with hepatocellular carcinoma after resection.

PMID- 26210787
TI  - Natural Compounds: DNA Methyltransferase Inhibitors in Oral Squamous Cell
      Carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is a multistep process which is modulated by
      several endogenous and environmental factors. Epigenetic changes have been found
      to be equally responsible for OSCC as genetic changes. A plethora of genes
      showing hypermethylation have been discovered in OSCC. Since these changes are
      reversible, a lot of emphasis is on using the natural compounds for their ability
      to cause demethylation which could lead to reactivation of the inactivated tumor
      suppressor genes. This review encompasses the promoter hypermethylation of tumor
      suppressor genes in OSCC and its possible reversal using natural compounds. In
      addition, new compounds which could be screened for their demethylating ability
      have also been proposed. 

PMID- 26210788
TI  - Mitochondrial biology: From molecules to diseases.
AB  - As an integral part of the cell, mitochondria play a pivotal role in the
      regulation of energy metabolism, signaling pathways, cell differentiation, cell
      proliferation and cell death. Mitochondrion with its own genetic material has
      characteristics distinct from those of the nuclear counterpart and its
      dysregulation is associated with a myriad of diseases. The discovery of interplay
      between the nuclear and mitochondrial genes, and various post-transcriptional
      modifications associated with their products has added excitement in the field.
      This has led to a better understanding of the basic mitochondrial function in
      normal and disease states, and is important for diagnosis and prognosis of a
      large number of disorders. The Fourth Annual Conference of Society for
      Mitochondrial Research and Medicine - India (SMRM) was titled "Mitochondrial
      Biology: from Molecules to Disease". The conference was organized by K.
      Satyamoorthy and K. Thangaraj at School of Life Sciences, Manipal University,
      Manipal, India, during 8-9 December, 2014. The aim of the conference was to bring
      researchers and clinicians to a common platform; create an opportunity for
      networking between laboratories; and to discuss about the recent development in
      mitochondrial biology, diagnosis, and therapy. This review summarizes the key
      outcomes of the conference. 

PMID- 26210789
TI  - Magnetic resonance evaluation in long term follow up of operated lateral tibial
      plateau fractures.
AB  - BACKGROUND: A lack of data exists on the long-term magnetic resonance imaging
      (MRI) findings after surgical repair of tibial plateau fractures (TPFs). We
      evaluated the MRI findings 13 to 31 years after surgical repair of TPFs, focusing
      especially on the pathological changes in the ligaments, menisci, and cartilage.
      METHODS: Twenty-three patients with 24 TPFs underwent open reduction and internal
      fixation with the same fork-shaped surgical plate that was used in our
      institution until 1999. No patient underwent preoperative or immediately
      postoperative MRI. The knees of all patients who underwent plate removal were
      examined by axial, coronal, and sagittal MRI. The Knee Injury and Osteoarthritis
      Outcome Score (KOOS) and whole-organ magnetic resonance score (WORMS) were
      determined in all patients. RESULTS: All 24 knees exhibited MRI abnormalities. An
      unexpectedly high number of pathological changes in the menisci and ligaments
      were observed. No meniscal or ligamentous injuries were documented at the time of
      the injury or initial surgery, but meniscal injuries manifested in the long term.
      MRI in almost all cases showed a damage to the lateral meniscal, the severity of
      which was related to the degree of tibial plateau widening, but not to the
      severity of the lateral joint surface impression. The overall condition of the
      knee joint was satisfactory as measured by the WORMS, and there was a weak
      correlation between WORMS and KOOS.

PMID- 26210790
TI  - Synthesis, Spectral Characteristics and DFT Studies of the New Dye 2,7-diacetyl-9
      ((dimethylamino)methylene)-9H-fluorene (DMMF) in Different Solvents.
AB  - The photophysical parameters such as electronic absorption spectra, molar
      absorptivity(epsilon), fluorescence spectra and fluorescence quantum yield (phif)
      of a new dye namely 2,7-diacetyl-9-((dimethylamino)methylene)-9H-fluorene (DMMF)
      were determined in different solvents. The electronic absorption are less
      sensitive to medium polarity. A bathochromic shift was observed in emission
      spectra(ca. 50 nm) upon increase of solvent polarity, which indicates that the
      singlet excited state (S1) of DMMF is more polar than the singlet ground state
      (So). Solid crystals of DMMF exhibit intense yellow fluorescence maximum at 550
      nm with bandwidth equal 64 nm upon excitation at wavelength 365 nm. The change in
      dipole moment value (DeltaMU) was calculated by using the variation of Stokes
      shift with solvent polarizability (Deltaf) (Lippert - Mataga plot) and was found
      to be 7.22 and 5.5 Debye for higher and lower energy of So - S1 (pi-pi*) H-1 -> L
      and So - S1 (pi-pi*) H -> L, respectively. These results show that, the excited
      state is more polar than the ground state. The net photochemical quantum yields
      of photodecomposition of DMMF (phic) were calculated as 7.2 * 10(-5), 1.14 * 10(
      4), 1.44 * 10(-4) and 2.11 * 10(-4) in different solvents such as MeOH, CH2Cl2,
      CHCl3 and CCl4, respectively. DFT/TD-DFT methods were used to study the geometric
      and electronic structures of DMMF in different solvents. A good agreement was
      found between the experimental and theoretical results.

PMID- 26210791
TI  - BASIC study: is intravaginal boric acid non-inferior to metronidazole in
      symptomatic bacterial vaginosis? Study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Bacterial vaginosis is associated with increased transmission of
      sexually transmitted infections, preterm labor, post-surgical infections, and
      endometritis. Current treatment for symptomatic bacterial vaginosis includes
      antibiotics, such as metronidazole, which are 70-80 % effective at one month
      after treatment and result in high recurrence rates and secondary candida
      infections. Intravaginal boric acid has been used for over a hundred years to
      treat vaginal infections, such as bacterial vaginosis. Boric acid is inexpensive,
      accessible, and has shown to be an effective treatment for other infections, such
      as vaginal candidiasis. To date, there has been no clinical trial evaluation of
      boric acid effectiveness to treat bacterial vaginosis. METHODS/DESIGN: The BASIC
      (Boric Acid, Alternate Solution for Intravaginal Colonization) trial is a
      randomized, double-blinded, multicenter study. The study will enroll a minimum of
      240 women of 16-50 years of age who are symptomatic with bacterial vaginosis.
      Eligible participants will have Amsel and Nugent scores confirming bacterial
      vaginosis. Women who are pregnant or menopausal or have other active co
      infections will be excluded. Consenting participants who meet exclusion and
      inclusion criteria will be randomly assigned to one of three treatment groups:
      boric acid, metronidazole, or an inert placebo. Self-administration of treatment
      intravaginally for 10 days will be followed by clinical assessment at 7 and 30
      days (days 17 and 40, respectively) after the end of the treatment phase. Primary
      outcome is a non-inferiority, per-protocol comparison of the effectiveness of
      boric acid with that of metronidazole at day 17, as measured by the Nugent score
      in 16-50 year olds. Secondary outcomes include: non-inferiority, intention-to
      treat comparison of effectiveness of boric acid with that of metronidazole at day
      17, analysis for both per-protocol and intention-to-treat at day 40, and safety
      considerations, including adverse effects requiring patient discontinuation of
      treatment. DISCUSSION: This study will be the first to determine whether
      intravaginal boric acid is non-inferior to metronidazole in the treatment of
      bacterial vaginosis in symptomatic women. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00799214, registered online Nov 10, 2008.

PMID- 26210792
TI  - Systolic and diastolic myocardial mechanics in hypertrophic cardiomyopathy and
      their link to the extent of hypertrophy, replacement fibrosis and interstitial
      fibrosis.
AB  - Aim of the present study was to investigate the relations between myocardial
      mechanics and the extent of hypertrophy and fibrosis in hypertrophic
      cardiomyopathy (HCM). Forty-five consecutive patients with HCM and 15 subjects
      without structural heart disease were included. Cardiac magnetic resonance with
      late gadolinium enhancement (LGE) imaging was performed to evaluate biventricular
      function, LV mass index and presence/extent of LGE, expression of replacement
      fibrosis. Myocardial T1 relaxation, a surrogate of interstitial fibrosis, was
      measured from Look-Locker sequence. Feature-tracking analysis was applied to LV
      basal, mid and apical short-axis images to assess systolic and diastolic global
      LV circumferential strain (CS) and strain rate (CSr). Peak systolic CS and CSr
      were significantly higher among HCM patients as compared to control subjects (p =
      0.015 and p = 0.007, respectively). The ratio of peak CSr during early filling to
      peak systolic CSr was significantly lower among HCM patients (p = 0.002). At
      multivariate linear regression analysis, LV mass index (p < 0.001) and %LV LGE (p
      = 0.011) were significantly and independently related to peak systolic CS; LV
      mass index (p < 0.001) and %LV LGE (p = 0.023) were significantly and
      independently related to peak systolic CSr; %LV LGE (p = 0.021) and T1 ratio (p =
      0.006) were significantly and independently related to the ratio of peak CSr
      during early filling to peak systolic CSr. LV systolic mechanics are enhanced and
      LV diastolic mechanics are impaired in HCM. Extent of hypertrophy and replacement
      fibrosis influence the LV systolic mechanics while extent of replacement fibrosis
      and interstitial fibrosis influence the LV diastolic mechanics.

PMID- 26210793
TI  - Practice Guideline: Epistaxis in Children.

PMID- 26210794
TI  - Response to "Re: Remote Ischemic Preconditioning to Reduce Contrast-induced
      Nephropathy: A Randomized Controlled Trial".

PMID- 26210795
TI  - Intensive care nurses' opinions and current practice in relation to delirium in
      the intensive care setting.
AB  - BACKGROUND: Delirium is a frequently encountered syndrome that negatively impacts
      on the well-being of the critically ill patient. Although international
      guidelines promote delirium monitoring, little is known regarding Irish intensive
      care (ICU) nurses' opinions and current practice in relation to delirium
      monitoring. AIM: To ascertain ICU nurses' opinions on delirium among the
      critically ill and establish if delirium monitoring is part of current practice
      in the Republic of Ireland. METHODS: A descriptive quantitative survey design was
      employed, utilising a self-report questionnaire. Participants were registered
      nurses selected using convenience sampling from two of the largest and leading
      teaching hospitals in the Republic of Ireland. The overall response rate was 70%
      (n=151/216). FINDINGS: The majority of participants 143 (95%) recognised delirium
      as a serious problem and 93% considered delirium to be an under-diagnosed
      syndrome that requires active medical intervention. Only 17.9% reported screening
      for delirium and 4% ranked delirium important to monitor in the ICU setting. The
      majority of participants never attended a lecture (79%) or read an article (68%)
      pertaining to delirium. CONCLUSION: The findings provide further evidence of the
      theory practice gap that is likely to exist internationally in settings where
      best practice guidelines on the management of delirium in the ICU setting are not
      implemented.

PMID- 26210796
TI  - Coupling spectroscopic and chromatographic techniques for evaluation of the
      depositional history of hydrocarbons in a subtropical estuary.
AB  - Spectroscopic and chromatographic techniques can be used together to evaluate
      hydrocarbon inputs to coastal environments such as the Paranagua estuarine system
      (PES), located in the SW Atlantic, Brazil. Historical inputs of aliphatic
      hydrocarbons (AHs) and polycyclic aromatic hydrocarbons (PAHs) were analyzed
      using two sediment cores from the PES. The AHs were related to the presence of
      biogenic organic matter and degraded oil residues. The PAHs were associated with
      mixed sources. The highest hydrocarbon concentrations were related to oil spills,
      while relatively low levels could be attributed to the decrease in oil usage
      during the global oil crisis. The results of electron paramagnetic resonance were
      in agreement with the absolute AHs and PAHs concentrations measured by
      chromatographic techniques, while near-infrared spectroscopy results were
      consistent with unresolved complex mixture (UCM)/total n-alkanes ratios. These
      findings suggest that the use of a combination of techniques can increase the
      accuracy of assessment of contamination in sediments. 

PMID- 26210797
TI  - Vasopressin inhibits mitogen-activated protein kinases and activated protein-1 in
      macrophages.
AB  - OBJECTIVES: We have previously shown that vasopressin could inhibit the
      upregulation of inflammatory mediators. Expression of inflammatory mediators is
      tightly regulated by the upstream transcriptional pathway mitogen-activated
      protein kinases (MAPKs) and activated protein-1 (AP-1). In this study, we
      elucidated whether vasopressin could inhibit the upregulation of MAPKs/AP-1.
      METHODS: Murine macrophages (RAW264.7 cells) randomly received lipopolysaccharide
      (LPS; 100 ng/mL) or LPS plus vasopressin (1000 pg/mL) (designated as the LPS and
      the LPS+V groups, respectively). Control groups were run simultaneously. For
      MAPKs, cells were harvested at 0 minutes, 15 minutes, 30 minutes, 45 minutes, and
      60 minutes after reaction. For AP-1, cells were harvested at 60 minutes after
      reaction. Between-group differences in MAPKs (i.e., extracellular regulated
      kinase, c-Jun N-terminal kinase, and p38 MAPK) and AP-1 expressions were
      compared. RESULTS: Immunoblotting assay data revealed that extracellular
      regulated kinase concentrations of the LPS+V group that harvested at 45 minutes
      and 60 minutes, but not at 15 minutes and 30 minutes, were significantly lower
      than those of the LPS group (p=0.005 and p=0.013). C-Jun N-terminal kinase
      concentrations of the LPS+V group that harvested at 15 minutes, 30 minutes, 45
      minutes, and 60 minutes were also significantly lower than those of the LPS group
      (all p<0.001). Concentrations of p38 MAPK of the LPS+V group that harvested at 15
      minutes, 30 minutes, and 45 minutes, but not at 60 minutes, were also
      significantly lower than those of the LPS group (all p<0.001). In addition,
      immunohistochemistry assay revealed that the AP-1 fluorescence signals of the
      LPS+V group were weaker than those of the LPS group. CONCLUSION: Vasopressin
      inhibits MAPKs and AP-1 in endotoxin-activated macrophages.

PMID- 26210798
TI  - APOA II genotypes frequency and their interaction with saturated fatty acids
      consumption on lipid profile of patients with type 2 diabetes.
AB  - BACKGROUND & AIM: Several studies have suggested that APOA II-265T/C polymorphism
      affect lipid profile. The aim of this study was to investigate the effect of 
      265T/C APOA II polymorphism and saturated fatty acids (SFA) intake interaction on
      lipid profile in diabetic population who are at risk for lipid disorders.
      METHODS: In this cross sectional study, 697 type 2 diabetic patients
      participated. Food consumption data were collected using validated semi
      quantitative FFQ during the last year. Realtime-PCR was used to determine APOA II
      265T/C genotypes. The interaction between the genotypes and SFA intake with lipid
      profile was tested using analysis of covariance (ANCOVA). RESULTS: According to
      APOA II-265T/C (rs5082) genotype distribution results, CC genotype with a
      frequency of 12.9% and TC with that of 47.7% showed the lowest and highest
      frequency in our population, respectively. CC genotype subjects had significantly
      lower total cholesterol, triglyceride, Cholesterol/HDL-c ratio and non-HDL
      cholesterol than T allele carriers (p = 0.009, p = 0.02, p = 0.02 and p = 0.002,
      respectively). The interaction between genotype and SFA intake contributed to
      significant higher levels of LDL-c and LDL/HDL in CCs (p = 0.05 and p = 0.01),
      suggesting vulnerability of these individuals to high intake of SFA in the diet.
      CONCLUSION: APOA II polymorphism may influence the saturated fatty acid intake
      required to prevent dyslipidemia in the type 2 diabetic population.

PMID- 26210799
TI  - Impact of Osteonecrosis of the Jaw on Osteoporosis Treatment in Japan: Results of
      a Questionnaire-Based Survey by the Adequate Treatment of Osteoporosis (A-TOP)
      Research Group.
AB  - Dentists request a discontinuation of antiresorptive agents, such as
      bisphosphonate, before and after tooth extractions to prevent osteonecrosis of
      the jaw (ONJ). However, little is known about how this affects ONJ and
      osteoporosis treatment and how medical professionals and dentists cooperate to
      treat ONJ in patients with osteoporosis. This study aimed to clarify the impact
      of ONJ on osteoporosis treatment in Japan. A structured questionnaire including
      14 key clinical queries was sent to 488 medical professionals as part of the
      Japanese Osteoporosis Intervention Trial (JOINT)-04, and 206 responses were
      received. A total of 173 respondents had received discontinuation requests from
      dentists. Of these, 28 respondents experienced 30 adverse events including ten
      fractures and one incidence of ONJ. The respondents who refused discontinuation
      requests observed no cases of ONJ. Approximately 16 % of respondents had patients
      who discontinued osteoporosis treatment, following a requested drug
      discontinuation, after tooth extraction. Dentists requested discontinuations for
      many medications that were not associated with the incidence of ONJ.
      Approximately 76 % of respondents had never requested oral health care from
      dentists before osteoporosis treatment and 72 % reported no cooperation between
      dentists and medical professionals in their region. Our results suggest that drug
      discontinuation may increase adverse events and disturb osteoporosis treatment
      without completely preventing ONJ. Currently, both medical professionals and
      dentists in Japan still continue to recommend their own treatment position. A
      forum to share information about ONJ among medical professionals, dentists, and
      patients is required.

PMID- 26210800
TI  - Nuclear model analysis of excitation functions of proton induced reactions on
      86Sr, 88Sr and natZr: Evaluation of production routes of 86Y.
AB  - The proton induced nuclear reactions on (86)Sr, (88)Sr and (nat)Zr were
      investigated for the production of (86)Y. The literature data were compared with
      the results of nuclear model calculations using the codes ALICE-IPPE, TALYS 1.6
      and EMPIRE 3.2. The thick target yields of (86)Y were calculated from the
      recommended excitation functions. Analysis of radioyttrium impurities was also
      performed. A comparison of the various production routes showed that for medical
      applications of (86)Y, the reaction (86)Sr(p,n)(86)Y is the method of choice,
      which gives efficient yield with minimum impurities. 

PMID- 26210801
TI  - Molecular mechanism for the substrate recognition of USP7.

PMID- 26210802
TI  - Escherichia coli endocarditis of native aortic valve and mitral valve.

PMID- 26210803
TI  - Incidence and Clinical Impact of Stent Fracture After PROMUS Element Platinum
      Chromium Everolimus-Eluting Stent Implantation.
AB  - OBJECTIVES: This study sought to assess the incidence and clinical impact of
      stent fracture (SF) after the PROMUS Element platinum-chromium everolimus-eluting
      stent (PtCr-EES). BACKGROUND: SF remains an unresolved, clinically relevant
      issue, even in the newer-generation drug-eluting stent era. METHODS: From March
      2012 to August 2013, 816 patients with 1,094 lesions were treated only with PtCr
      EES and 700 patients (85.7%) with 898 lesions undergoing follow-up angiography
      within 9 months after the index procedure were analyzed. SF was defined as
      complete or partial separation of the stent, as assessed by plain fluoroscopy,
      intravascular ultrasound, or optical coherence tomography during the follow-up.
      We assessed the rate of SF and the cumulative incidence of clinically driven
      target lesion revascularization and definite stent thrombosis within 9 months
      after the index procedure. RESULTS: SF was observed in 16 of 898 lesions (1.7%)
      and 16 of 700 patients (2.2%). Lesions with in-stent restenosis at baseline (odds
      ratio [OR]: 14.2, 95% confidence intervals [CI]: 5.09 to 39.7; p < 0.001) or
      hinge motion (OR: 4.31, 95% CI: 1.12 to 16.5; p = 0.03), and total stent length
      (per 10-mm increase; OR: 1.32, 95% CI: 1.12 to 1.57; p = 0.001) were predictors
      of SF. Cumulative incidence of clinically driven target lesion revascularization
      within 9-months was numerically higher in the SF group than that in the non-SF
      group (18.7% vs. 2.3%). Cumulative incidence of definite stent thrombosis within
      9 months after the index procedure was similar between the SF and non-SF groups
      (0.0% vs. 0.23%). CONCLUSIONS: SF after PtCr-EES occurs in 1.7% of lesions and
      appears to be associated with clinically driven target lesion revascularization.

PMID- 26210804
TI  - Percutaneous Closure of Right Ventricular Pseudoaneurysm.

PMID- 26210805
TI  - Local Hemodynamics: An Innocent Bystander or a Critical Factor Regulating
      Neoatherosclerotic Evolution?

PMID- 26210806
TI  - Final 5-Year Follow-Up of a Randomized Controlled Trial of Everolimus- and
      Paclitaxel-Eluting Stents for Coronary Revascularization in Daily Practice: The
      COMPARE Trial (A Trial of Everolimus-Eluting Stents and Paclitaxel Stents for
      Coronary Revascularization in Daily Practice).
AB  - OBJECTIVES: This study sought to report the 5-year outcomes of everolimus-eluting
      stents (EES) and paclitaxel-eluting stents (PES) in an all-comers population
      undergoing percutaneous coronary intervention (PCI). BACKGROUND: The medium-term
      1 and 2-year results of the prospective randomized COMPARE trial (A Trial of
      Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary
      Revascularization in Daily Practice) showed superior clinical outcomes with EES
      compared with PES in an all-comers PCI population. Whether this benefit is
      sustained over longer-term follow-up is unknown. Furthermore, systematic long
      term follow-up data on these metallic drug eluting stents with durable polymers
      are scarce. METHODS: We randomly assigned 1,800 patients undergoing PCI to EES or
      PES. The pre-specified composite primary endpoint was death, myocardial
      infarction (MI), or target vessel revascularization (TVR). RESULTS: Follow-up at
      5 years was completed in 1,791 (99.5%) patients. Treatment with EES compared with
      PES led to a relative risk reduction of the primary endpoint by 27% (18.4% vs.
      25.1%, p = 0.0005), driven by lower rates of MI (7.0% vs. 11.5%, p = 0.001) and
      TVR (7.4% vs. 11.4%, p = 0.003), but not with mortality (9.0% vs. 10.3%, relative
      risk 0.88, p = 0.36). Moreover, patients treated with EES compared with PES had
      lower rates of definite/probable stent thrombosis at 5 years (3.1% vs. 5.9%, p =
      0.005). The hazard curves for TVR, MI, and stent thrombosis diverge over the
      first 3 years and, subsequently, progress in parallel. CONCLUSIONS: The early-
      and medium-term superiority of EES over PES measured both by safety and efficacy
      endpoints is sustained at 5 years in this all-comer population. (A Trial of
      Everolimus-Eluting Stents and Paclitaxel-Eluting Stents for Coronary
      Revascularization in Daily Practice [COMPARE]; NCT01016041).

PMID- 26210807
TI  - Illuminating Culprit Plaque Histology by Optical Coherence Tomography: Shedding
      New Light on Old Insights.

PMID- 26210808
TI  - Effect of Vascular Access Site Choice on Radiation Exposure During Coronary
      Angiography: The REVERE Trial (Randomized Evaluation of Vascular Entry Site and
      Radiation Exposure).
AB  - OBJECTIVES: This study sought to perform a randomized noninferiority trial of
      radiation exposure during cardiac catheterization comparing femoral access (FA)
      with left radial access (LRA) and right radial access (RRA). BACKGROUND:
      Increased radiation exposure with radial approach compared with femoral approach
      remains a controversial issue. METHODS: This study randomized 1,493 patients
      undergoing cardiac catheterization at a tertiary care center to FA, LRA, and RRA
      in a 1:1:1 fashion. The primary endpoint was air kerma. The secondary endpoints
      included dose-area product, fluoroscopy time and operator dose per procedure,
      number of cineangiograms, and number of catheters. RESULTS: Baseline and
      procedural characteristics were similar among groups. No significant differences
      were observed in air kerma (medians: FA: 421 mGy [interquartile range (IQR): 337
      to 574 mGy], LRA: 454 mGy [IQR: 331 to 643 mGy], and RRA: 483 mGy [IQR: 382 to
      592 mGy], p = 0.146), dose-area product (medians: FA: 25.5 Gy cm(2) [IQR: 19.6 to
      34.5 Gy cm(2)], LRA: 26.6 Gy cm(2) [IQR: 19.5 to 37.5 Gy cm(2)], and RRA: 27.7 Gy
      cm(2) [IQR: 21.9 to 34.4 Gy cm(2)], p = 0.40), or fluoroscopy time (medians: FA:
      1.3 min [IQR: 1.0 to 1.7 min], LRA: 1.3 min [IQR: 1.0 to 1.7 min], and RRA: 1.32
      min [IQR: 1.0 to 1.7 min], p = 0.19) among the 3 access sites. Median operator
      exposure was higher in the LRA group (3 mrem [IQR: 2 to 5 mrem], p = 0.001 vs.
      FA, and p = 0.0001 vs. RRA) compared with the FA (2 mrem [IQR: 2 to 4 mrem] and
      RRA groups (3 mrem [IQR: 2 to 5 mrem]). CONCLUSIONS: Radiation exposure to
      patients was similar during diagnostic coronary angiography with FA, RRA, and
      LRA. However, LRA was associated with significantly higher operator radiation
      exposure than were FA and RRA procedures. (Randomized Evaluation of Vascular
      Entry Site and Radiation Exposure [REVERE]; NCT01677481).

PMID- 26210809
TI  - KAEA (SUDPRO), a member of the ubiquitous KEOPS/EKC protein complex, regulates
      the arginine catabolic pathway and the expression of several other genes in
      Aspergillus nidulans.
AB  - The kaeA(KAE1) (suDpro) gene, which was identified in Aspergillus nidulans as a
      suppressor of proline auxotrophic mutations, encodes the orthologue of
      Saccharomyces cerevisiae Kae1p, a member of the evolutionarily conserved
      KEOPS/EKC (Kinase, Endopeptidase and Other Proteins of Small size/Endopeptidase
      like and Kinase associated to transcribed Chromatin) complex. In yeast, this
      complex has been shown to be involved in tRNA modification, transcription, and
      genome maintenance. In A. nidulans, mutations in kaeA result in several
      phenotypic effects, the derepression of arginine catabolism genes, and changes in
      the expression levels of several others, including genes involved in amino acid
      and siderophore metabolism, sulfate transport, carbon/energy metabolism,
      translation, and transcription regulation, such as rcoA(TUP1), which encodes the
      global transcriptional corepressor. 

PMID- 26210810
TI  - The DnaJ OsDjA7/8 is essential for chloroplast development in rice (Oryza
      sativa).
AB  - DnaJ proteins belong to chaperones of Hsp40 family that ubiquitously participate
      in various cellular processes. Previous studies have shown chloroplast-targeted
      DnaJs are involved in the development of chloroplast in some plant species.
      However, little is known about the function of DnaJs in rice, one of the main
      staple crops. In this study, we characterized a type I DnaJ protein OsDjA7/8. We
      found that the gene OsDjA7/8 was expressed in all collected tissues, with a
      priority in the vigorous growth leaf. Subcellular localization revealed that the
      protein OsDjA7/8 was mainly distributed in chloroplast. Reduced expression of
      OsDjA7/8 in rice led to albino lethal at the seedling stage. Transmission
      electron microscopy observation showed that the chloroplast structures were
      abnormally developed in the plants silenced for OsDjA7/8. In addition, the
      transcriptional expression of the genes tightly associated with the development
      of chloroplast was deeply reduced in the plants silenced for OsDjA7/8.
      Collectively, our study reveals that OsDjA7/8 encodes a chloroplast-localized
      protein and is essential for chloroplast development and differentiation in rice.

PMID- 26210811
TI  - Cockayne Syndrome due to a maternally-inherited whole gene deletion of ERCC8 and
      a paternally-inherited ERCC8 exon 4 deletion.
AB  - Cockayne Syndrome (CS) is an autosomal recessive disorder that causes
      neurological regression, growth failure and dysmorphic features. We describe a
      Chinese female child with CS caused by deletions of exon 4 of ERCC8 on one
      chromosome and exons 1-12 on the other chromosome. By using chromosomal
      microarray, multiplex ligation-dependant probe analysis and long range PCR, we
      showed that she inherited a 277 kb deletion affecting the whole ERCC8 gene from
      the mother and a complex rearrangement resulting in deletion of exon 4 together
      with a 1,656 bp inversion of intron 4 from the father. A similar complex
      rearrangement has been reported in four unrelated Japanese CS patients. Analysis
      of the deletion involving exon 4 identified LINE and other repeat elements that
      may predispose the region to deletions, insertions and inversions. The patient
      also had insulin-dependent diabetes mellitus, a rare co-existing feature in
      patients with CS. More research will be needed to further understand the
      endocrine manifestations in CS patients.

PMID- 26210812
TI  - Pathogenesis of canine distemper virus in experimentally infected raccoon dogs,
      foxes, and minks.
AB  - Canine distemper virus (CDV) infects a broad range of carnivores and causes a
      highly contagious disease with severe immunosuppression. The disease severity
      markedly varies in different species. To investigate the pathogenesis of CDV in
      raccoon dog (Nyctereutes procyonoides), fox (Vulpes vulpes) and mink (Neovison
      vison) species, three groups of CDV sero-negative animals were infected with CDV
      strain LN(10)1. This CDV strain belongs to the Asia-1 genotype, which is
      epidemiologically predominant in carnivores in China. CDV infection provoked
      marked differences in virulence in the three species that were studied. Raccoon
      dogs developed fever, severe conjunctivitis, and pathological lesions, with 100%
      (5/5) mortality and with high viral RNA loads in organs within 15 days post
      infection (dpi). In infected foxes, the onset of the disease was delayed, with
      40% (2/5) mortality by 21 dpi. Infected minks developed only mild clinical signs
      and pathological lesions, and mortality was not observed. Raccoon dogs and foxes
      showed more severe immune suppression (lymphopenia, decreased lymphocyte
      proliferation, viremia and low-level virus neutralizing antibodies) than minks.
      We also observed a distinct pattern of cytokine mRNA transcripts at different
      times after infection. Decreased IFN-gamma and IL-4 mRNA responses were evident
      in the animals with fatal disease, while up-regulation of these cytokines was
      observed in the animals surviving the infection. Increased TNF-alpha response was
      detected in animals with mild or severe clinical signs. Based on the results, we
      could distinguish three different patterns of disease after experimental CDV
      infection, e.g. a mild form in minks, a moderate form in foxes and a severe
      disease in raccoon dogs. The observed differences in susceptibility to CDV could
      be related to distinct host cytokine profiles. Comparative evaluation of CDV
      pathogenesis in various animal species is pivotal to generate models suitable for
      the evaluation of CDV-host interactions and of vaccine response.

PMID- 26210813
TI  - Mapping of brain macromolecules and their use for spectral processing of (1)H
      MRSI data with an ultra-short acquisition delay at 7 T.
AB  - Long echo time (TE) MR spectroscopy (MRS) sequences are sensitive only to
      metabolites of low molecular weight. At shorter TE, significantly more metabolite
      signals are detectable, including broad signals of high-molecular-weight
      macromolecules (MMs). Although the presence of MM resonances can bias metabolite
      quantification at short TE, proper quantification of MMs is important since MMs
      themselves may serve as potentially valuable biomarkers for many pathologies. We
      have therefore developed an FID-based 2D-MR Spectroscopic Imaging (2D-MRSI)
      sequence to map MMs in healthy brain tissue at 7 T within a scan time of ~17 min
      and a repetition time of 879 ms. This 2D-MRSI technique provides MM maps over a
      whole slice (i.e., including cortical gray matter) at an ultra-short acquisition
      delay of 1.3 ms, using double inversion for efficient nulling of low-molecular
      weight metabolites. The optimal sequence parameters were estimated using Bloch
      simulations, phantom testing, and in vivo validation. The acquired in vivo MM
      spectra (n=6) included nine distinct MM peaks in the range of ~0.9-3.7 ppm. The
      measured average MM spectrum was incorporated into the LCModel basis set and
      utilized for further quantification of MRSI data sets without metabolite nulling,
      which were acquired in five additional volunteers. The quantification results for
      two basis sets, one including the MMs and one without MM spectrum, were compared.
      Due to the high spectral resolution and full signal detection provided by the FID
      MRSI sequence, we could successfully map five important brain metabolites. Most
      quantified metabolite signal amplitudes were significantly lower since the
      inclusion of MMs into the basis set corrected the overestimation of metabolite
      signals. The precision of fit (i.e., Cramer Rao lower bounds) remained unchanged.
      Our MM maps show that the overall MM contribution was higher in gray matter than
      in white matter. In conclusion, the acquired MM spectrum improved the accuracy of
      metabolite quantification and allowed the acquisition of high spatial resolution
      maps of five major brain metabolites and also MMs.

PMID- 26210814
TI  - Susceptibility to everyday cognitive failure is reflected in functional network
      interactions in the resting brain.
AB  - The proneness to minor errors and slips in everyday life as assessed by the
      Cognitive Failures Questionnaire (CFQ) constitutes a trait characteristic and is
      reflected in stable features of brain structure and function. It is unclear,
      however, how dynamic interactions of large-scale brain networks contribute to
      this disposition. To address this question, we performed a high model order
      independent component analysis (ICA) with subsequent dual regression on resting
      state fMRI data from 71 subjects to extract temporal time courses describing the
      dynamics of 17 resting-state networks (RSN). Dynamic network interactions between
      all 17 RSN were assessed by linear correlations between networks' time courses.
      On this basis, we investigated the relationship between subject-level RSN
      interactions and the susceptibility to everyday cognitive failure. We found that
      CFQ scores were significantly correlated with the interplay of the cingulo
      opercular network (CON) and a posterior parietal network which unifies clusters
      in the posterior cingulate, precuneus, intraparietal lobules and middle temporal
      regions. Specifically, a higher positive functional connectivity between these
      two RSN was indicative of higher proneness to cognitive failure. Both the CON and
      posterior parietal network are implicated in cognitive functions, such as tonic
      alertness and executive control. Results indicate that proper checks and balances
      between the two networks are needed to protect against cognitive failure.
      Furthermore, we demonstrate that the study of temporal network dynamics in the
      resting state is a feasible tool to investigate individual differences in
      cognitive ability and performance. 

PMID- 26210815
TI  - Cardiac-CT and Cardiac-MR examinations cost analysis, based on data of four
      Italian Centers.
AB  - PURPOSE: To establish the appropriate number of Cardiac-CT and Cardio-MR
      examinations, to determine an economically justified and sustainable investment
      in these two technologies, for an exclusive cardiologic use. MATERIALS AND
      METHODS: From July 2013 to July 2014, through a survey in four different Italian
      Departments of Radiology, data on the costs of Cardiac-CT and Cardiac-MR
      examinations were collected. For the evaluation of the costs of examinations, it
      was used an analytical accounting system, considering only the direct costs
      (consumables, health personnel work time, equipment amortization/maintenance) and
      other costs (utilities, services, etc.). Indirect costs (general costs) were not
      assessed. It was made a simulation, assuming an exclusive use of the CT and MR
      equipments for Cardiac-CT and Cardiac-MR examinations, calculating the annual
      number necessary to arrive at the Break Even Point (BEP: the point at which cost
      or expenses and revenue are equal). RESULTS: On the basis of the CT costs, in
      order to reach the BEP, performing only Cardiac-CT examinations, an average of
      2641-2752 examinations/year is needed. The annual time commitment of the Medical
      Professional to ensure the number of examinations to reach the BEP is 2625-2750
      h/year, equivalent to two Medical Doctors in a Cardiology Department. The recent
      Cardiac-CT Italian Registry, in the period January-June 2011, reports a number of
      examinations of 3455 patients in 47 different Centers, distributed throughout the
      whole national territory. With regard to MR, in order to reach the BEP,
      performing only Cardiac-MR examinations, an average of 2435-3123
      examinations/year is needed. The annual time commitment of the Medical
      Professional to ensure the number of examinations to reach the BEP is 2437-3125
      h/year, equivalent to two Medical Doctors in a Cardiology Department. The recent
      Cardiac-MR Italian Registry reports a number of examinations of 3776 patients in
      40 Centers, distributed throughout the whole national territory. CONCLUSION: This
      research has shown that, only on the basis of costs, currently in Italy is anti
      economic an exclusive use of CT or MR equipment for cardiac exams, unless it's
      not decided, regardless of the recent guidelines and clinical indications, to
      submit all patients with cardiac diseases (diseases of the coronary arteries and
      cardiomyopathies) to Cardiac-CT and Cardiac-MR examinations. This might likely to
      increase both the inappropriate examinations and either health spending and in
      the case of CT with important repercussions, in terms of radio-exposure, subject
      to forensic procedures.

PMID- 26210816
TI  - Impacts of mercury exposure on life history traits of Tigriopus japonicus:
      Multigeneration effects and recovery from pollution.
AB  - Here, through a multigenerational life-cycle test, Tigriopus japonicus were
      exposed to different mercuric chloride treatments in seawater (nominal
      concentrations of 0, 0.5, 1, 10, and 50MUg/L) for five successive generations (F0
      F4), and subsequently all the treatments were recovered in clean environments for
      one generation (F5). Six life history traits (survival, developmental time for
      nauplius phase, developmental time to maturation, fecundity, number of clutches,
      and number of nauplii/clutch) were examined for each generation. Mercury (Hg)
      accumulation was also analyzed for the adult copepods in the F1, F3, and F5. The
      results indicated that Hg accumulated in a dose-dependent manner for the F1, F3,
      and F5 generations. Moreover, higher Hg contents were observed in F3 than F1 at
      the same exposure levels. Among the six life history traits, only fecundity and
      number of nauplii/clutch showed a greater sensitivity to Hg toxicity, and the
      inhibitory effects worsened from F0 to F3, which was explained by a trend for
      higher metal accumulation with increasing generations. In the recovery generation
      (F5), none of the traits differed from the control, highlighting that Hg might
      not induce any epigenetic or parental effects in the following generations. Thus,
      we hypothesized that although cumulative effects might have been involved in Hg
      multigenerational toxicity, physiological acclimation, that is, phenotypic
      plasticity could explain Hg tolerance obtained by marine copepods. Impacts on
      important life history traits could disturb the population dynamics of some
      important marine copepods, hence having unexpected ecological consequences in the
      marine ecosystem. Yet, the Hg harmful impacts rapidly fade away as the Hg is
      cleared from the environment. 

PMID- 26210817
TI  - Long-term and 'patient-reported' outcomes of total esophagogastric dissociation
      versus laparoscopic fundoplication for gastroesophageal reflux disease in the
      severely neurodisabled child.
AB  - AIM: Fundoplication has high failure rates in neurodisability: esophagogastric
      dissociation (TOGD) has been proposed as an alternative. This study aimed to
      compare the long-term and 'patient-reported' outcomes of TOGD and laparoscopic
      fundoplication (LapFundo). METHODS: Matched cohort comparison comprises (i)
      retrospective analysis from a prospective database and (ii) carer questionnaire
      survey of symptoms and quality of life (CP-QoL-Child). Children were included if
      they had severe neurodisability (Gross Motor Function Classification System five)
      and spasticity. RESULTS: Groups were similar in terms of previous surgery and
      comorbidities. The TOGD group was younger (22 vs. 31.5months, p=0.038) with more
      females (18/23 vs. 11/24, p=0.036). TOGD was more likely to require intensive
      care: operative time, length of stay and time to full feeds were all longer
      (p<0.0001). Median follow-up was 6.3 and 5.8years. Rates of complications were
      comparable. Symptom recurrence (5/24 vs. 1/23, p=0.34) and use of acid-reducing
      medication (13/24 vs. 4/23, p=0.035) were higher for LapFundo. Carer-reported
      symptoms and QoL were similar. CONCLUSIONS: TOGD had similar efficacy to LapFundo
      (with suggestion of lower failure), with comparable morbidity and carer-reported
      outcomes. However, TOGD was more 'invasive,' requiring longer periods of
      rehabilitation. Families should be offered both procedures as part of
      comprehensive preoperative counseling.

PMID- 26210818
TI  - The evaluation of deglutition with videofluoroscopy after repair of esophageal
      atresia and/or tracheoesophageal fistula.
AB  - AIM: A retrospective study was performed to evaluate the functional disorders of
      deglutition with videofluoroscopy (VFS), in children operated for esophageal
      atresia (EA) and/or tracheoesophageal fistula (TEF). METHODS: Patients with the
      repair of EA-TEF were evaluated in respect to the type of malformation, operative
      procedure, postoperative complications, deglutitive and respiratory symptoms, and
      gastroesophageal reflux disease (GERD). The dysphagia score, VFS findings of
      oral, pharyngeal and esophageal phases, and penetration-aspiration scale (PAS)
      score were recorded in the evaluation of the deglutitive functions. RESULTS:
      Thirty-two cases with a median age of 48months (2-120months), and male to female
      ratio of 14:18 were included in the study. Most of the cases had Gross type C
      anomaly (n=26, 81.3%), and the others were type A (n=3), D (n=2) and E (n=1). The
      incidence of associated anomalies was 71.8%. The patients underwent primary
      (n=26, 81.3%) or delayed (n=6, 18.7%) anastomosis. Postoperative complications
      including anastomotic stricture (n=12), leak (n=2) and recurrent fistula (n=2)
      were managed by dilatation, conservative approach and repair of the fistula,
      respectively. Recurrent pneumonia (n=13), cough with liquid intake (n=10) and
      food impaction (n=7) were recorded in the history. Management of GERD included
      medical (n=11) and surgical (n=7) treatment. The median dysphagia score was 3.5
      (min: 0-max: 27). The oral phase of VFS was normal in most of the cases (n=29,
      90.6%). Only three had mild or moderate impairment, and none had severe. The
      pharyngeal phase showed no impairment in 23 of the cases (71.8%), and severe
      impairment was observed only in 3 of all, for the parameters of hyolaryngeal
      elevation and airway closure. Opposite to the first two phases of the
      deglutition, the esophageal phase was normal in only 2 of the cases (6.3%). Among
      the other 30 cases with impairment, only two had mild, and the rest had moderate
      to severe problems. Esophageal backflow, motility and residue were the most
      severely impaired parameters of this phase. The PAS evaluation revealed no
      penetration and aspiration in 26 of the cases (81.3%), while 1 had penetration
      and five had aspiration. CONCLUSION: The patients with repaired EA-TEF may reveal
      deglutitive and respiratory symptoms in follow-up, necessitating certain
      investigations. The deglutition is functionally evaluated with VFS. While the
      disorders of oral and pharyngeal phases are less frequent and prominent, the
      esophageal phase reveals disorders with higher incidence and severity.

PMID- 26210819
TI  - Impact of Community-Based Integrated Traditional Chinese and Western Medicine
      Metabolic Syndrome Intervention Technology in Rural Residents in Southern
      Jiangsu, China.
AB  - BACKGROUND: To explore the feasibility and efficiency of community-based
      integrated traditional Chinese medicine (TCM) and Western medicine metabolic
      syndrome (MS) intervention in rural residents. MATERIAL AND METHODS: The MS
      intervention was administered to 598 rural community residents aged 45 years and
      older in Zhoushi from 2011 to 2013. Subjects completed a health examination and
      health behavior questionnaire before and after the intervention. In the
      intervention, we designed a "healthy life self-help program" using TCM
      appropriate technologies for the subjects. RESULTS: After 2 years of intervention
      by means of integrated traditional Chinese and Western medicine, 57.0% (341
      persons) of the subjects no longer suffered from MS. The recovery rate of BMI,
      blood pressure, FBG, TG, and HDL-C were 22.1%, 40.5%, 37.9%, 32.8%, and 62.4%,
      respectively. There were statistically significant differences in exercise,
      smoking, and alcohol drinking between baseline and 2 years later. CONCLUSIONS:
      The integrated traditional Chinese and Western medicine MS intervention was
      effective in deceasing most of the parameters of MS, especially blood pressure,
      and helping people to do more exercise. The program would be useful to implement
      in other similar populations.

PMID- 26210820
TI  - [Phytovigilance: A medical requirement and a legal obligation].
AB  - Phytovigilance consists in supervision of side effects and drug interactions
      consequential to use of herbal medicinal products, herbal food supplements,
      herbal cosmetics and/or medicinal plants. It includes thus pharmacovigilance
      applied to phytotherapy, nutrivigilance and cosmetovigilance but also
      addictovigilance in case of plants, which lead to drug addiction, and
      toxicovigilance in case of toxic plants. Becoming necessary owing to (acute or
      chronic) toxicity risks or to drug interactions risks (of pharmacocinetical or
      pharmacodynamical kind)--as far as it concerns interactions between several
      associated plants or between a plant and a chemical or biotechnological
      allopathic medicine--phytovigilance represents moreover a legal obligation.
      Pharmacovigilance--in case of herbal medicinal products--is indeed becoming
      mandatory according to title IX of the European directive 2001/83/EC, whereas
      nutrivigilance is imposed by the European Food Safety Agency (EFSA).

PMID- 26210821
TI  - New investigations into the genotoxicity of cobalt compounds and their impact on
      overall assessment of genotoxic risk.
AB  - The genotoxicity of cobalt metal and cobalt compounds has been widely studied.
      Several publications show induction of chromosomal aberrations, micronuclei or
      DNA damage in mammalian cells in vitro in the absence of S9. Mixed results were
      seen in gene mutation studies in bacteria and mammalian cells in vitro, and in
      chromosomal aberration or micronucleus assays in vivo. To resolve these
      inconsistencies, new studies were performed with soluble and poorly soluble
      cobalt compounds according to OECD-recommended protocols. Induction of
      chromosomal damage was confirmed in vitro, but data suggest this may be due to
      oxidative stress. No biologically significant mutagenic responses were obtained
      in bacteria, Tk(+/-) or Hprt mutation tests. Negative results were also obtained
      for chromosomal aberrations (in bone marrow and spermatogonia) and micronuclei at
      maximum tolerated doses in vivo. Poorly soluble cobalt compounds do not appear to
      be genotoxic. Soluble compounds do induce some DNA and chromosomal damage in
      vitro, probably due to reactive oxygen. The absence of chromosome damage in
      robust GLP studies in vivo suggests that effective protective processes are
      sufficient to prevent oxidative DNA damage in whole mammals. Overall, there is no
      evidence of genetic toxicity with relevance for humans of cobalt substances and
      cobalt metal.

PMID- 26210822
TI  - Using gene expression profiling to evaluate cellular responses in mouse lungs
      exposed to V2O5 and a group of other mouse lung tumorigens and non-tumorigens.
AB  - Many compounds test positive for lung tumors in two-year NTP carcinogenicity
      bioassays in B6C3F1 mice. V2O5 was identified as a lung carcinogen in this assay,
      leading to its IARC (International Agency for Research on Cancer) classification
      as group 2b or a "possible" human carcinogen. To assess potential tumorigenic
      mode of action of V2O5, we compared gene expression and gene ontology enrichment
      in lung tissue of female B6C3F1 mice exposed for 13 weeks to a V2O5 particulate
      aerosol at a tumorigenic level (2.0 mg/m(3)). Relative to 12 other compounds also
      tested for carcinogenicity in 2-year bioassays in mice, there were 1026
      differentially expressed genes with V2O5, of which 483 were unique to V2O5.
      Ontology analysis of the 1026 V2O5 differentially expressed genes showed
      enrichment for hyaluronan and sphingolipid metabolism, adenylate cyclase
      functions, c-AMP signaling and PKA activation/signaling. Enrichment of
      lipids/lipoprotein metabolism and inflammatory pathways were consistent with
      previously reported clinical findings. Enrichment of c-AMP and PKA signaling
      pathways may arise due to inhibition of phosphatases, a known biological action
      of vanadate. We saw no enrichment for DNA-damage, oxidative stress, cell cycle,
      or apoptosis pathway signaling in mouse lungs exposed to V2O5 which is in
      contrast with past studies evaluating in vivo gene expression in target tissues
      of other carcinogens (arsenic, formaldehyde, naphthalene and chloroprene).

PMID- 26210823
TI  - Cytoskeletal regulation of platelet formation: Coordination of F-actin and
      microtubules.
AB  - Platelets are small, anucleate blood cells which play an important role in
      haemostasis. Thrombocytopenia is a condition where the platelet count falls below
      150*10(9)/l and patients suffering from severe forms of this condition can
      experience life-threatening bleeds requiring platelet transfusions. Platelets are
      produced from large progenitor cells called megakaryocytes which are found in the
      bone marrow. The process of megakaryocyte maturation and the formation of
      proplatelets are essential steps in the production of mature platelets and both
      depend heavily on the actin and microtubule cytoskeletons. Understanding these
      processes is important for the development of in vitro platelet production which
      will help to treat thrombocytopenia as well as produce model systems for studying
      platelet-associated disorders. This review will highlight some of the recent
      advances in our understanding of the role of the cytoskeleton in platelet
      production, especially the key molecules and signalling pathways that regulate
      actin and microtubule crosstalk. 

PMID- 26210824
TI  - Specific and general facets of hoarding: A bifactor model.
AB  - Whereas it has been suggested that hoarding is a multidimensional construct
      comprising distinct but interrelated factors (i.e., difficulty discarding,
      excessive clutter, and excessive acquisition), a high degree of overlap as well
      as a lack of discriminant validity among these factors and exogenous constructs
      suggests that a correlated factors approach may not adequately capture this
      phenomenon. The factor structure of the Saving Inventory Revised (SIR) was
      examined in a large non-selected clinic sample (N=490). A bifactor model of
      hoarding, comprising a general Hoarding factor and orthogonal Urge-Related
      Acquiring, Distress-Related Acquiring, Difficulty Discarding, and Clutter factors
      fit the data best. Further, whereas the general Hoarding factor was related to
      several depression facets, the specific hoarding factors demonstrated
      differential relations with depression. This study establishes that acquiring
      behaviors are motivated by both positive/urge-related and negative/distress
      related emotions. Additionally, general and distinct factors should be considered
      to properly contextualize hoarding behavior. 

PMID- 26210825
TI  - Determination of Organothiophosphate Insecticides in Environmental Water Samples
      by a Very Simple and Sensitive Spectrofluorimetric Method.
AB  - A simple, rapid and sensitive spectrofluorimetric method was developed for the
      determination of di-syston, ethion and phorate in environmental water samples.
      The procedure is based on the oxidation of these pesticides with cerium (IV) to
      produce cerium (III), and its fluorescence was monitored at 368 +/- 3 nm after
      excitation at 257 +/- 3 nm. The variables effecting oxidation of each pesticide
      were studied and optimized. Under the experimental conditions used, the
      calibration graphs were linear over the range 0.2-15, 0.1-13, 0.1-13 ng mL(-1)
      for di-syston, ethion and phorate, respectively. The limit of detection and
      quantification were in the range 0.034-0.096 and 0.112-0.316 ng mL(-1),
      respectively. Intra- and inter-day assay precisions, expressed as the relative
      standard deviation (RSD), were lower than 5.2 % and 6.7 %, respectively. Good
      recoveries in the range 86 %-108 % were obtained for spiked water samples. The
      proposed method was applied to the determination of studied pesticides in
      environmental water samples. 

PMID- 26210826
TI  - Assessment of the Pollutants in Soils and Surface Waters Around Gumuskoy Silver
      Mine (Kutahya, Turkey).
AB  - Heavy metal concentrations in surface water and soil samples around Gumuskoy
      Silver Mine, located in Kopruoren Basin, were determined to evaluate the
      anthropogenic level of contamination due to mining activities. The mean
      concentrations of As, Pb, Sb and Cd in 12 soil samples came out to be 1193, 844,
      66 and 19 ppm, respectively. Soil pollution assessment was carried out by using
      geoaccumulation index (Igeo), enrichment factor (EF) and pollution index (PI).
      Igeo, EF and PI suggest anthropogenic pollution of As, Pb, Sb and Zn in the areas
      where there is leakage of these heavy metals from the waste pools of the silver
      mine facility. Water samples collected from the surface waters also have elevated
      concentrations of these heavy metals. The contaminants are most probably
      transported by surface waters in the rainy season.

PMID- 26210827
TI  - Metal Content in Four Shellfish Species from the Istrian Coast of Croatia.
AB  - The concentrations of As, Cd, Cu, Hg, Pb and Zn were measured in four shellfish
      species (oysters, mussels, scallops, warty venus) collected along the Istria
      Peninsula coast during autumn 2013. Mean metal levels in shellfish ranged as
      follows (mg/kg): As 1.69-3.91, Cd 0.15-0.99, Hg 0.06-0.2, Pb 0.33-0.74, Cu 1.23
      36.2, Zn 16.3-511. Statistical analysis showed a significant difference in As
      (p<0.05), Cd, Pb, Hg, Cu and Zn (p<0.01, all) levels among shellfish species. The
      highest metal concentrations were found in oysters (mg/kg): As 3.91, Cd 0.99, Cu
      36.2 and Zn 511. The highest means of Pb and Hg were measured in (mg/kg): warty
      venus 0.74; scallops 0.12. The estimated daily intakes for oysters shown it as a
      good source of Cu and Zn. The higher contribution of Cd and As levels to the
      provisional tolerable weekly intake in shellfishes suggest a careful approach for
      consumption.

PMID- 26210835
TI  - 50 Years Ago in The Journal of Pediatrics: Hypoventilation and Cor Pulmonale Due
      to Chronic Upper Airway Obstruction.

PMID- 26210834
TI  - Delaying the Pediatric Fellowship Start Date to Improve Trainee Well-Being.

PMID- 26210836
TI  - 50 Years Ago in The Journal of Pediatrics: Cardiopulmonary Effects of Placental
      Transfusion.

PMID- 26210837
TI  - 50 Years Ago in The Journal of Pediatrics: Phenylketonuria in a Negro Infant.

PMID- 26210838
TI  - 50 Years Ago in The Journal of Pediatrics: A Controlled Study of Imipramine
      (Tofranil) in the Treatment of Childhood Enuresis.

PMID- 26210839
TI  - 50 Years Ago in The Journal of Pediatrics: Reversible Pulmonary Hypertension in a
      Child with Respiratory Obstruction and Cor Pulmonale.

PMID- 26210840
TI  - 50 Years Ago in The Journal of Pediatrics: Congenital Rubella Syndrome: New
      Clinical Aspects with Recovery of Virus from Affected Infants.

PMID- 26210841
TI  - 50 Years Ago in The Journal of Pediatrics: Hurler's Disease, Morquio's Disease
      and Related Mucopolysaccharidoses.

PMID- 26210842
TI  - Early Enteral Nutrition and Aggressive Fluid Resuscitation are Associated with
      Improved Clinical Outcomes in Acute Pancreatitis.
AB  - OBJECTIVES: To determine whether recommendations for treatment of acute
      pancreatitis (AP) in adults impact the outcomes of pediatric AP. STUDY DESIGN:
      Adult guidelines regarding early management of AP were implemented through an
      admission order set at Cincinnati Children's Hospital Medical Center at the
      beginning of the year 2014. Recommendations included administering high rates of
      intravenous fluid (IVF) within 24 hours of admission and enteral nutrition within
      48 hours of admission. A retrospective chart review of AP admissions before and
      after the implementation of the recommendations was undertaken. Outcomes studied
      were: hospital length of stay, intensive care unit transfer rates, development of
      severe AP, pulmonary complications, and readmission rates post discharge from the
      hospital. RESULTS: The study included 201 patients. Children who received feeds
      within the first 48 hours and received greater than maintenance IVF within 24
      hours had a shorter length of stay, less intensive care unit admissions and
      severe AP rates compared with the patients who remained nil per os during the
      first 48 hours and received lower rates of IVF. CONCLUSION: Our data support that
      early enteral nutrition and early aggressive IVF improve outcomes of pediatric
      AP.

PMID- 26210843
TI  - 50 Years Ago in The Journal of Pediatrics: Some Recently Recognized
      Manifestations of the Rubella Syndrome.

PMID- 26210844
TI  - A New Interactive Screening Test for Autism Spectrum Disorders in Toddlers.
AB  - OBJECTIVE: To develop a clinically valid interactive level 2 screening assessment
      for autism spectrum disorders (ASD) in toddlers that is brief, easily
      administered, and scored by clinicians. STUDY DESIGN: We describe the
      development, training, standardization, and validation of the Rapid Interactive
      Screening Test for Autism in Toddlers (RITA-T) with ASD-specific diagnostic
      instruments. The RITA-T can be administered and scored in 10 minutes. We studied
      the validity of the RITA-T to distinguish between toddlers with ASD from toddlers
      with developmental delay (DD)/non-ASD in an early childhood clinic. We also
      evaluated the test's performance in toddlers with no developmental concerns. We
      identified a cutoff score based on sensitivity, specificity, and positive
      predictive value of the RITA-T that best differentiates between ASD and DD/non
      ASD. RESULTS: A total of 61 toddlers were enrolled. RITA-T scores were correlated
      with ASD-specific diagnostic tools (r = 0.79; P < .01) and ASD clinical diagnoses
      (r = 0.77; P < .01). Mean scores were significantly different in subjects with
      ASD, those with DD/non-ASD, and those with no developmental concerns (20.8 vs 13
      vs 10.6, respectively; P < .0001). At a cutoff score of >14 , the RITA-T had a
      sensitivity of 1.00, specificity of 0.84, and positive predictive value of 0.88
      for identifying ASD risk in a high-risk group. CONCLUSION: The RITA-T is a
      promising new level 2 interactive screening tool for improving the early
      identification of ASD in toddlers in general pediatric and early intervention
      settings and allowing access to treatment.

PMID- 26210845
TI  - Improving Care through Better Communication: Continuing the Debate.

PMID- 26210846
TI  - A call for a value based approach to laboratory medicine funding.
AB  - All areas of healthcare, including pathology, are being challenged by the reality
      that the days of ever increasing budgets are over and the key debate is about how
      to provide value for money. As originally described by Porter and Tiesberg, value
      based healthcare is defined as maximising outcomes over cost by moving away from
      fee for service models to ones that reward providers on the basis of outcomes
      (1). While production efficiencies will continue to evolve, the opportunities for
      future stepwise improvements in production costs are likely to have diminished.
      The focus now is on delivering improved testing outcomes in a relatively cost
      neutral or at least cost effective way. This brings pathology into line with
      other health services that focus on value for money for payers, and maximising
      health outcomes for consumers. This would signal a break from the existing
      pathology funding model, which does not directly recognise or reward the
      contribution of pathology towards improved health outcomes, or seek to
      decommission tests that offer little clinical value. Pathology has a direct
      impact on clinical and economic outcomes that extend from testing and it is
      important to garner support for a new approach to funding that incentivises
      improvements of the overall quality and contribution of the pathology service. 

PMID- 26210847
TI  - Percentage of hyperdense cells: Automated parameter to hereditary spherocytosis
      screening.
AB  - BACKGROUND: The hereditary spherocytosis (HS) is a common cause of inherited
      hemolytic anemia that is difficult to identify in many cases. Currently, there
      are new economic parameters for red cell disorder evaluation, such as hyperdense
      cell percentage (%Hyper) obtained from automated analyzers. OBJECTIVE: In this
      study we determined the %Hyper efficacy and compared its accuracy with a flow
      cytometry method in HS, hemoglobinopathy and healthy individuals, in order to
      allow the use of %Hyper in HS screening. METHODS: Patients treated at the
      outpatient clinic at the Hospital de Clinicas de Porto Alegre (HCPA) were
      allocated into three groups according to their clinical condition: HS,
      hemoglobinopathy or healthy groups. Flow-cytometric osmotic fragility test (FCM
      OF) method was used as reference to compare with %Hyper, both performed from
      K2EDTA samples. RESULTS: Fifty-eight individuals were included in this study. We
      found that the %Hyper cut-off point of 6.4% showed an excellent sensitivity
      (92.3%) and specificity (90.7%) to detect HS. Besides, %Hyper presented a
      significant negative correlation with FCM OF in identifying HS (Rs=-0.525;
      P<0.001). CONCLUSIONS: %Hyper could be a tool for screening HS, before requesting
      additional tests. It is a fast and cost-effective test, which is easily obtained
      in complete blood count, favoring its use in clinical laboratories. However, this
      test does not replace flow cytometric methods for confirmation of atypical cases.

PMID- 26210848
TI  - Association of status redox with demographic, clinical and imaging parameters in
      patients with Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative
      disorder, caused by an expanded trinucleotide CAG sequence of the huntingtin
      (Htt) gene, which encodes a stretch of glutamines in the Htt protein. The
      mechanisms of neurodegeneration associated with the accumulation of Htt
      aggregates still remains unclear. OBJECTIVES: To determine oxidative stress
      biomarkers in HD patients and their relationship with clinical, demographic and
      neuroimaging parameters. DESIGN AND METHODS: Fourteen patients and 39 controls
      paired by age and sex participated in this study. Oxidative damage was assayed in
      blood by measuring malondialdehyde (MDA) and advanced oxidative protein products
      (AOPPs). Antioxidant status was determined by activities of superoxide dismutase
      (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR),
      reduced glutathione (GSH), protein thiols and total antioxidant capacity (FRAP).
      The Unified Huntington Disease Rating Scale (UHDRS) and neuroimaging studies were
      also employed. RESULTS: MDA, AOPP and GPx were significantly increased in HD
      patients with respect to the control group, while GR activity was decreased. FRAP
      correlated with age of disease onset, AOPP with motor severity (UHDRS score), age
      of patients and age of disease onset. Caudate atrophy was associated with lower
      plasma concentrations of GSH. CONCLUSIONS: These findings point to a redox
      imbalance in HD patients. GR activity could be a potential biomarker for symptom
      onset in asymptomatic gene carriers, while plasmatic GSH could be useful in
      monitoring the progression of neurodegeneration - as an expression of caudate
      atrophy - during the course of the disease.

PMID- 26210849
TI  - Development and evaluation of analytical performance of a fully automated
      chemiluminescent immunoassay for protein induced by vitamin K absence or
      antagonist II.
AB  - OBJECTIVES: Protein induced by vitamin K absence or antagonist II (PIVKA-II), an
      abnormal form of prothrombin, has been used as an aid in the diagnosis of
      hepatocellular cancer (HCC) as a tumor marker. We developed a fully automated
      quantitative immunoassay for PIVKA-II on the ARCHITECT(r) i systems. The aim of
      this study was to evaluate the analytical performance of this assay. DESIGN AND
      METHOD: Assay imprecision, sensitivity, dilution linearity, high dose hook
      effect, sample type equivalency, assay interferences of potential interfering
      materials and correlation with Picolumi PIVKA-II (Eidia, Tokyo, Japan) were
      evaluated. RESULTS: The percentage coefficient of variation (%CV) of total
      imprecision ranged from 2.8% to 5.4% with 10 levels of samples. The limit of
      blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) were less
      than 0.63 mAU/mL, 1.62 mAU/mL, and 8.25 mAU/mL, respectively. Linearity up to
      30,000 mAU/mL, no high dose hook effect, no difference among sample types and no
      interference of common drugs and endogenous substances were observed. Correlation
      study with the Picolumi PIVKA-II gave a correlation coefficient of 0.93 and a
      regression slope of 1.07. CONCLUSIONS: The results demonstrate that the fully
      automated prototype ARCHITECT PIVKA-II assay is an accurate, highly sensitive and
      precise assay for the measurement of PIVKA-II levels in human sera and plasmas.

PMID- 26210850
TI  - Reliability of the modified Gross Motor Function Measure-88 (GMFM-88) for
      children with both Spastic Cerebral Palsy and Cerebral Visual Impairment: A
      preliminary study.
AB  - PURPOSE: The aims of this study were to adapt the Gross Motor Function Measure-88
      (GMFM-88) for children with Cerebral Palsy (CP) and Cerebral Visual Impairment
      (CVI) and to determine the test-retest and interobserver reliability of the
      adapted version. METHOD: Sixteen paediatric physical therapists familiar with CVI
      participated in the adaptation process. The Delphi method was used to gain
      consensus among a panel of experts. Seventy-seven children with CP and CVI (44
      boys and 33 girls, aged between 50 and 144 months) participated in this study. To
      assess test-retest and interobserver reliability, the GMFM-88 was administered
      twice within three weeks (Mean=9 days, SD=6 days) by trained paediatric physical
      therapists, one of whom was familiar with the child and one who wasn't.
      Percentages of identical scores, Cronbach's alphas and intraclass correlation
      coefficients (ICC) were computed for each dimension level. RESULTS: All experts
      agreed on the proposed adaptations of the GMFM-88 for children with CP and CVI.
      Test-retest reliability ICCs for dimension scores were between 0.94 and 1.00,
      mean percentages of identical scores between 29 and 71, and interobserver
      reliability ICCs of the adapted GMFM-88 were 0.99-1.00 for dimension scores. Mean
      percentages of identical scores varied between 53 and 91. Test-retest and
      interobserver reliability of the GMFM-88-CVI for children with CP and CVI was
      excellent. Internal consistency of dimension scores lay between 0.97 and 1.00.
      CONCLUSION: The psychometric properties of the adapted GMFM-88 for children with
      CP and CVI are reliable and comparable to the original GMFM-88.

PMID- 26210852
TI  - Enzymatic selective synthesis of 1,3-DAG based on deep eutectic solvent acting as
      substrate and solvent.
AB  - In this study, enzymatic selective esterification of oleic acid with glycerol
      based on deep eutectic solvent acting as substrate and solvent was studied. As
      choline chloride (ChCl) or betaine can effectively change the chemical reaction
      characteristics of glycerol when they are mixed with a certain molar ratio of
      glycerol, several factors crucial to the lipase catalytic esterification of
      glycerol with oleic acid was investigated. Results showed that, betaine had more
      moderate effects than ChCl on the lipase, and water content had an important
      influence of the esterification and the enzyme selectivity. Significant changes
      of the glyceride compositions and enzyme selectivity were found in ChCl adding
      system compared with pure glycerol system; optimum accumulation of DAG especially
      1,3-DAG because of the eutectic effect of ChCl was found in this system.
      Furthermore, in a model 1,3-DAG esterification synthesis system catalyzed by
      Novozym 435, high content (42.9 mol%) of the 1,3-DAG could be obtained in ChCl
      adding system within 1 h. 

PMID- 26210851
TI  - Neurodevelopmental outcome after surgery for acyanotic congenital heart disease.
AB  - BACKGROUND: Inconsistent results on neuropsychological outcome in patients
      treated for acyanotic congenital heart disease (aCHD) questioned the clinical
      relevance of possible neurobehavioral sequelae in this group. This study was
      designed to objectify the neuropsychological profile and evaluate associations
      with medical data. METHODS: Patients with a corrected atrial or ventricular
      septal defect, ASD-II or VSD, (n=46; mean age 9 years, 2 months) and a matched
      control group were submitted to an intelligence test (Wechsler Intelligence Scale
      for Children, third edition, Dutch version) and evaluated with a
      neuropsychological test battery (Developmental Neuropsychological Assessment,
      second edition, Dutch version). Hospitalization variables were retrieved to
      evaluate associations with cognitive outcome. Parents completed a behavioral
      checklist (Achenbach Child Behavior Checklist for Children aged 6-18). RESULTS:
      ASD-II patients showed lower scores in domains of visuospatial processing,
      language, attention, and social perception. VSD patients displayed subtle
      problems in attention and visuospatial information processing. Only few
      perioperative medical factors, but also socioeconomic variables were associated
      with cognitive outcomes. Parents of ASD-II patients reported more school problems
      when compared to controls. CONCLUSIONS: After treatment for aCHD, subtle
      cognitive difficulties can present in domains of visuospatial information
      processing, language, attention, and social perception. These shortcomings might
      hamper school performances, as is suggested by lower school competence ratings.
      Ongoing follow-up and cognitive screening is warranted to promote developmental
      progress, in which both parents and clinicians share responsibility.

PMID- 26210853
TI  - Database of RNA binding protein expression and disease dynamics (READ DB).
AB  - RNA Binding Protein (RBP) Expression and Disease Dynamics database (READ DB) is a
      non-redundant, curated database of human RBPs. RBPs curated from different
      experimental studies are reported with their annotation, tissue-wide RNA and
      protein expression levels, evolutionary conservation, disease associations,
      protein-protein interactions, microRNA predictions, their known RNA recognition
      sequence motifs as well as predicted binding targets and associated functional
      themes, providing a one stop portal for understanding the expression,
      evolutionary trajectories and disease dynamics of RBPs in the context of post
      transcriptional regulatory networks.

PMID- 26210854
TI  - Spatio-temporal dynamics of beta-tubulin isotypes during the development of the
      sensory auditory organ in rat.
AB  - There are different beta-tubulin isoforms in microtubules of vertebrate tissues.
      However, their functional significance is still largely unknown. In the present
      study, we investigated the localization of five beta-tubulin isotypes (beta1-5)
      within the hearing organ during development in rat. By using confocal microscopy,
      we showed that with the exception of the beta3-tubulin isoform that was specific
      to nerve fibres, all the different beta-tubulin isoforms were mainly present in
      the supporting cells. Contrary to beta1-4-tubulins, we also found that the beta5
      tubulin isoform appeared only at a key stage of the post-natal development in
      specific cell types (pillar cells and Deiters' cells). By using transmission
      electron microscopy, we revealed further that this developmental stage coincided
      with the formation of two separate bundles of microtubules from a unique one in
      these supporting cells. Together, these results suggest that the beta5-tubulin
      isoform might be involved in the generation of new microtubule bundles from a pre
      existing one. 

PMID- 26210855
TI  - Impaired extracellular matrix structure resulting from malnutrition in
      ovariectomized mature rats.
AB  - Bone loss is a symptom related to disease and age, which reflects on bone cells
      and ECM. Discrepant regulation affects cell proliferation and ECM localization.
      Rat model of osteoporosis (OVX) was investigated against control rats (Sham) at
      young and old ages. Biophysical, histological and molecular techniques were
      implemented to examine the underlying cellular and extracellular matrix changes
      and to assess the mechanisms contributing to bone loss in the context of aging
      and the widely used osteoporotic models in rats. Bone loss exhibited a
      compromised function of bone cells and infiltration of adipocytes into bone
      marrow. However, the expression of genes regulating collagen catabolic process
      and adipogenesis was chronologically shifted in diseased bone in comparison with
      aged bone. The data showed the involvement of Wnt signaling inhibition in
      adipogenesis and bone loss due to over-expression of SOST in both diseased and
      aged bone. Further, in the OVX animals, an integrin-mediated ERK activation
      indicated the role of MAPK in osteoblastogenesis and adipogenesis. The increased
      PTH levels due to calcium and estrogen deficiency activated osteoblastogenesis.
      Thusly, RANKL-mediated osteoclastogenesis was initiated. Interestingly, the data
      show the role of MEPE regulating osteoclast-mediated resorption at late stages in
      osteoporotic bone. The interplay between ECM and bone cells change tissue
      microstructure and properties. The involvement of Wnt and MAPK pathways in
      activating cell proliferation has intriguing similarities to oncogenesis and
      myeloma. The study indicates the importance of targeting both pathways
      simultaneously to remedy metabolic bone diseases and age-related bone loss. 

PMID- 26210856
TI  - Diffusion of Intervention Effects: The Impact of a Family-Based Substance Use
      Prevention Program on Friends of Participants.
AB  - PURPOSE: We tested whether effects of the Strengthening Families Program for
      Youth 10-14 (SFP10-14) diffused from intervention participants to their friends.
      We also tested which program effects on participants accounted for diffusion.
      METHODS: Data are from 5,449 students (51% female; mean initial age = 12.3 years)
      in the PROmoting School-community-university Partnerships to Enhance Resilience
      community intervention trial (2001-2006) who did not participate in SFP10-14
      (i.e., nonparticipants). At each of five waves, students identified up to seven
      friends and self-reported past month drunkenness and cigarette use, substance use
      attitudes, parenting practices, and unsupervised time spent with friends. We
      computed two measures of indirect exposure to SFP10-14: total number of SFP
      attending friends at each wave and cumulative proportion of SFP-attending friends
      averaged across the current and all previous post-intervention waves. RESULTS:
      Three years post-intervention, the odds of getting drunk (odds ratio = 1.4) and
      using cigarettes (odds ratio = 2.7) were higher among nonparticipants with zero
      SFP-attending friends compared with nonparticipants with three or more SFP
      attending friends. Multilevel analyses also provided evidence of diffusion:
      nonparticipants with a higher cumulative proportion of SFP-attending friends at a
      given wave were less likely than their peers to use drugs at that wave. Effects
      from SFP10-14 primarily diffused through friendship networks by reducing the
      amount of unstructured socializing (unsupervised time that nonparticipants spent
      with friends), changing friends' substance use attitudes, and then changing
      nonparticipants' own substance use attitudes. CONCLUSIONS: Program developers
      should consider and test how interventions may facilitate diffusion to extend
      program reach and promote program sustainability.

PMID- 26210857
TI  - Cumulative oxytocin dose during induction of labor according to maternal body
      mass index.
AB  - OBJECTIVE: To determine the cumulative oxytocin dose needed to achieve vaginal
      delivery among obese and non-obese women. METHODS: A retrospective study was
      undertaken of women with singleton, term (>=37 weeks) pregnancies who delivered
      at an institution in California, USA, between May 1 and July 31, 2012. Women were
      deemed to be obese when their body mass index (BMI; calculated as weight in
      kilograms divided by the square of height in meters) was 30 or above. Cumulative
      oxytocin doses were calculated for women who achieved vaginal delivery. RESULTS:
      Overall, 413 women were included. Among 357 women for whom BMI data were
      available, 204 (57.1%) were obese. Vaginal delivery was achieved in 379 women.
      Among women who received augmentation after spontaneous labor onset, obese women
      trended towards more cumulative oxytocin (minimum: 24.7 +/- 100.5 mU among women
      with a BMI of 18.50-24.99; maximum: 1580.5 +/- 2530.5 mU among women with a BMI
      of 35.00-39.99; P=0.086). Women who underwent induction of labor required
      significantly more oxytocin with increasing BMI class (P<0.001), despite no
      difference in length of labor. CONCLUSION: Obese women required a larger
      cumulative oxytocin dose to achieve vaginal birth during labor induction, but not
      during augmentation of labor. The physiology of spontaneous labor could supersede
      or influence the metabolic derangement facing obese patients undergoing induction
      of labor.

PMID- 26210858
TI  - Secondary osteoporosis in collagen-induced arthritis rats.
AB  - Numerous studies have demonstrated that rheumatoid arthritis (RA) is often
      associated with bone loss; however, few experiments have focused on cancellous
      and cortical bone changes in rats during the process of arthritis. We have
      investigated bone changes in rats with collagen-induced arthritis (CIA) and have
      explored the characteristics of how RA induces osteoporosis by means of bone
      histomorphometry, bone biomechanics studies, bone mineral density studies, micro
      computer tomography, enzyme-linked immunosorbant assay, immunohistochemistry, and
      Western blot analysis. Bone mineral density of the femur and lumbar vertebrae and
      biomechanical properties of the femur were decreased in CIA rats. Trabecular bone
      volume of the tibia and lumbar vertebrae was decreased whereas bone resorption
      was increased in CIA rats. Bone formation of the tibial shaft in periosteal
      surfaces was decreased in CIA rats. Furthermore, the trabecular bone loss in CIA
      rats was severer at 16 weeks than at 8 weeks, as was cortical bone loss. The
      serum level of tumor necrosis factor alpha in CIA rats was increased, and the
      expression of dickkopf 1 and that of receptor activator of nuclear factor kappaB
      (RANKL) ligand (RANKL) in the ankle joints were also increased, but the
      expression of osteoprotegerin (OPG) was decreased. We conclude that CIA rats
      developed systemic osteoporosis, and that osteoporosis became more serious with
      CIA development. The mechanism may be related to the increase of bone resorption
      in cancellous bone cause by upregulation of the expression of DKK-1 and
      regulation of the RANKL/RANK/OPG signaling pathway, and the decrease of bone
      formation in cortical bone caused by an increase in the expression of DKK-1. 

PMID- 26210859
TI  - Positive change following adversity and psychological adjustment over time in
      abused foster youth.
AB  - Many foster youth experience maltreatment in their family-of-origin and
      additional maltreatment while in foster care. Not surprisingly, rates of
      depression are higher in foster youth than the general population, and peak
      during ages 17-19 during the stressful transition into adulthood. However, no
      known studies have reported on whether foster youth perceive positive changes
      following such adversity, and whether positive change facilitates psychological
      adjustment over time. The current study examined components of positive change
      (i.e., compassion for others and self-efficacy) with depression severity from age
      17 to 18 as youth prepared to exit foster care. Participants were youth from the
      Mental Health Service Use of Youth Leaving Foster Care study who endorsed child
      maltreatment. Components of positive change and severity of abuse were measured
      initially. Depression was measured initially and every three months over the
      following year. Latent growth curve modeling was used to examine the course of
      depression as a function of initial levels of positive change and severity of
      abuse. Results revealed that decreases in depression followed an inverse
      quadratic function in which the steepest declines occurred in the first three
      months and leveled off after that. Severity of abuse was positively correlated
      with higher initial levels of depression and negatively correlated with decreases
      in depression. Greater self-efficacy was negatively associated with initial
      levels of depression and predicted decreases in depression over the year, whereas
      compassion for others was neither associated with initial depression nor changes
      in depression. Implications for intervention, theory, and research are discussed.

PMID- 26210860
TI  - Phase-Resolved Doppler Optical Coherence Tomographic Features in Retinal
      Angiomatous Proliferation.
AB  - PURPOSE: To study patients diagnosed with retinal angiomatous proliferation (RAP)
      based on conventional imaging techniques with phase-resolved Doppler optical
      coherence tomography (OCT) to detect and localize blood flow in RAP lesions; and
      to compare these findings to conventional imaging, which are mostly invasive and
      give limited information concerning intra- and transretinal blood flow. DESIGN:
      Single-center, consecutive observational case series. METHODS: Twelve treatment
      naive patients diagnosed with RAP based on fundus examination, fluorescein
      angiography, and indocyanine green angiography were included. Median age was 79
      years (range 65-90). Patients were imaged with an experimental 1040 nm swept
      source phase-resolved Doppler OCT instrument. Abnormal flow was defined as
      intraretinal neovascularization or retinal choroidal anastomosis. RESULTS: In 11
      patients adequate phase-resolved Doppler OCT images were obtained showing
      abnormal blood flow in the RAP lesion. In 4 patients a retinal choroidal
      anastomosis was found, 3 patients showed intraretinal neovascularization
      connected with a pigment epithelial detachment, 2 patients showed only
      intraretinal neovascularization, and in 2 patients flow was limited to the
      subretinal or sub-retinal pigment epithelial space. CONCLUSIONS: Phase-resolved
      Doppler OCT is able to detect and localize abnormal blood flow within RAP
      lesions. Blood flow was mostly confined to the intraretinal structures with or
      without a connecting pigment epithelial detachment; in one-third of patients a
      retinal choroidal anastomosis was detected. The potential of angiography with
      phase-resolved Doppler OCT to accurately distinguish between normal and
      pathologic blood flow in addition to structural OCT data without invasive
      procedures will help to further elucidate both retinal and choroidal vascular
      pathologies like RAP.

PMID- 26210861
TI  - Age, Sex, and Ethnic Variations in Inner and Outer Retinal and Choroidal
      Thickness on Spectral-Domain Optical Coherence Tomography.
AB  - PURPOSE: To evaluate age, sex, and ethnic variations in inner and outer retinal
      and choroidal thickness and foveal pit, using spectral-domain optical coherence
      tomography (SD OCT). DESIGN: Single-center observational cross-sectional study.
      METHODS: Ninety randomly selected, healthy individuals of white, black, and South
      Asian origin underwent SD OCT raster and enhanced depth imaging scan. Manual
      measurements of inner and outer retinal thickness and choroidal thickness up to 3
      mm nasal and temporal to the fovea were performed. The age, sex, and ethnic
      differences in these parameters were analyzed. RESULTS: The mean inner retinal
      thickness was lower by approximately 12 MUm in black subjects across the central
      retina compared to white subjects (P < .05). The central foveal thickness below
      the foveal pit was lower in eyes of blacks compared to South Asians (12 MUm, P =
      .035) and white subjects (18 MUm, P < .0001). The fovea was also significantly
      wider in eyes of black and South Asian subjects compared to white individuals.
      The inner retinal thickness decreased by 0.5 MUm per year of age of subjects and
      was thinner by 6.1 MUm (P < .02) in female compared to male subjects. The
      subfoveal choroidal thickness did not vary between ethnic groups but the temporal
      choroid was significantly thinner in black subjects (P < .05). The choroid showed
      an age-related decline in thickness of 2 MUm per year of age of the subjects.
      CONCLUSIONS: Interethnic differences include wider fovea, lower central foveal
      thickness, and thinner inner retina in eyes of black subjects compared to their
      white and South Asian counterparts.

PMID- 26210862
TI  - The Effect of Achieving Immediate Target Angle on Success of Strabismus Surgery
      in Children.
AB  - PURPOSE: To determine if achieving the ideal postoperative target range increases
      the long-term success of pediatric strabismus surgery. DESIGN: Interventional
      case series. METHODS: Children below 12 years old with horizontal strabismus who
      underwent surgical correction by recession, resection, advancement, or a
      combination of both between 1996 and 2011 were included. Alignment was measured
      within 1 week and at a minimum of 6 months after surgery. The ideal postoperative
      target range was defined as 0-8 prism diopters (PD) of esotropia in exotropic
      patients and within 4 PD of orthotropia in esotropic patients measured within 1
      week after the surgery. Success was defined as a measurement within 10 PD of
      orthotropia at the latest postoperative visit. The main outcome measures were
      surgical success rate and the factors affecting it. RESULTS: We included 352
      patients with mean follow-up of 18 months. Overall, patients within the target
      range had a higher success rate than those outside it (75.6% vs 57% P = .0004).
      This was highly significant for exotropia (P = .0002) but not for esotropia (P =
      .4). Multiple regression analysis revealed that being within target range was the
      strongest predictor of long-term success (odds ratio [OR] = 2.3, range 1.4-3.7).
      Overall, surgeries on patients with esotropia were more likely to be successful
      than on those with exotropia (OR = 1.9, range 1.2-3), and premature patients had
      poorer outcomes (OR = 0.2, range 0.1-0.8). CONCLUSION: Achieving the ideal target
      range within 1 week after surgery is associated with a high rate of long-term
      success in exotropia surgery in children.

PMID- 26210863
TI  - Cataract Surgery Outcomes in Glaucomatous Eyes: Results From the Veterans Affairs
      Ophthalmic Surgery Outcomes Data Project.
AB  - PURPOSE: To compare visual acuity outcomes, vision-related quality of life, and
      complications related to cataract surgery in eyes with and without glaucoma.
      DESIGN: Retrospective cohort study. METHODS: Cataract surgery outcomes in cases
      with and without glaucoma from the Veterans Affairs Ophthalmic Surgical Outcomes
      Data Project were compared. RESULTS: We identified 608 glaucoma cases and 4306
      controls undergoing planned cataract surgery alone. After adjusting for age,
      pseudoexfoliation, small pupil, prior ocular surgery, and anterior chamber depth,
      we found that glaucoma cases were more likely to have posterior capsular tear
      with vitrectomy (odds ratio [OR] 1.8, P = .03) and sulcus intraocular lens
      placement (OR 1.65, P = .03) during cataract surgery. Glaucoma cases were more
      likely to have postoperative inflammation (OR 1.73, P < .0001), prolonged
      elevated intraocular pressure (OR 2.96, P = .0003), and additional surgery within
      30 days (OR 1.92, P = .03). Mean best-corrected visual acuity (BCVA) and Visual
      Function Questionnaire (VFQ) scores significantly improved after cataract surgery
      in both groups (P < .0001), but there were larger improvements in BCVA (P = .01)
      and VFQ composite scores (P < .0001) in the nonglaucoma vs the glaucoma group. A
      total of 3621 nonglaucoma cases (94.1%) had postoperative BCVA 20/40 or better,
      compared to 466 glaucoma cases (89.6%) (P = .0003). CONCLUSIONS: Eyes with
      glaucoma are at increased risk for complications and have more modest visual
      outcomes after cataract surgery compared to eyes without glaucoma. Despite this,
      glaucoma patients still experience significant improvement in vision-related
      outcomes after cataract extraction. Further study is needed to explore potential
      factors that influence cataract surgery outcomes in glaucomatous eyes.

PMID- 26210864
TI  - Comparison of Intraocular Pressure Measurements Obtained by Rebound, Noncontact,
      and Goldmann Applanation Tonometry in Children.
AB  - PURPOSE: To compare intraocular pressure (IOP) among rebound, noncontact, and
      Goldmann applanation tonometry (GAT) and their relationships to central corneal
      thickness in children. DESIGN: Diagnostic protocol comparison and evaluation.
      METHODS: In right eyes of 419 children, mean IOP, rates of successful measurement
      with 3 tonometries, and intermethod agreement by Bland-Altman plot were assessed.
      The influences of central corneal thickness, and of average IOP of 3 tonometries
      on IOP differences between tonometries, were evaluated. RESULTS: The mean age was
      8.89 +/- 3.41 years (3-15 years). There was significant difference in mean IOP of
      each tonometry; GAT showed the lowest values (P < .05). The IOP was successfully
      measured by noncontact tonometry in 89%, by rebound tonometry in 75%, and by GAT
      in 64% of children less than 10 years old, and in 100%, 98%, and 94% of children
      older than 10 years, respectively. The IOP of each tonometer positively
      correlated with central corneal thickness (P < .05). The mean differences and
      limits of agreement were 0.81 +/- 6.19 mm Hg (noncontact minus rebound), 2.56 +/-
      4.62 mm Hg (rebound minus GAT), and 1.81 +/- 4.76 mm Hg (noncontact minus GAT).
      Rebound and noncontact tonometry overestimated IOP relative to GAT for thicker
      central corneal thicknesses. Rebound tonometry overestimated IOP relative to GAT
      and noncontact tonometry at higher average IOP of 3 tonometries. CONCLUSIONS:
      Rebound, noncontact, and Goldmann applanation tonometries can be considered
      appropriate methods for children, though noncontact tonometry is the most
      accessible. Given the risk of false-positive diagnosis of pediatric glaucoma,
      attention should be devoted to children with IOP within a suspicious range or
      thicker cornea.

PMID- 26210865
TI  - Retinal Pigment Epithelial Tear After Intravitreal Ranibizumab Treatment for
      Retinal Angiomatous Proliferation.
AB  - PURPOSE: To evaluate the incidence and associated risk factors of retinal pigment
      epithelium (RPE) tears after intravitreal ranibizumab injection treatment for
      retinal angiomatous proliferation (RAP). DESIGN: Retrospective, observational
      case series. METHODS: Ninety-eight treatment-naive RAP eyes (86 patients) that
      received intravitreal ranibizumab injections were included. All patients were
      treated with an initial series of 3 monthly loading injections, followed by
      further injections as required. Baseline characteristics and features were
      evaluated as potential risk factors for RPE tearing. The visual and anatomic
      outcomes after treatment were evaluated at 12 months from baseline. RESULTS: RPE
      tears had developed in 8.2% (8) of the eyes by 12 months. Of these, all had
      pigment epithelium detachment (PED) at baseline, and the majority (7) had
      developed an RPE tear within 3 months. Multiple regression analysis showed that
      higher PED (odds ratio [OR] = 1.411, 95% confidence interval [CI] = 1.199-1.888,
      P = .011) and thinner choroid (OR = 0.815, 95% CI = 0.719-0.912, P = .023) were
      associated with a higher risk of RPE tearing. The mean best-corrected visual
      acuity of the patients with RPE tearing (0.56 +/- 0.49 logarithm of the minimal
      angle of resolution [logMAR]) was significantly worse at 12 months than that of
      patients without RPE tearing (0.74 +/- 0.55 logMAR, P = .009) after treatment.
      CONCLUSIONS: RPE tears developed in 8.2% of eyes with RAP during the 12 months
      following ranibizumab injections. Higher PED height and thinner subfoveal
      choroidal thickness were associated with the development of RPE tears after
      ranibizumab treatment for RAP.

PMID- 26210866
TI  - Terrien Marginal Degeneration: Clinical Characteristics and Outcomes.
AB  - PURPOSE: To describe outcomes of patients with Terrien marginal degeneration.
      DESIGN: Retrospective case series. METHODS: Database review of 25 patients (43
      eyes) seen over 10 years (2004-2013) at Toronto Western Hospital cornea clinic.
      Outcome measures included demographics, location of disease, topographic
      astigmatism, visual acuity, coexisting ocular disease, and surgical management.
      RESULTS: Mean age at presentation was 44 years (range, 20-82 years) and 54% were
      male. Eighteen patients (72%) had bilateral disease. Mean follow-up was 30.3
      months. Mean topographic astigmatism was 4.02 diopters (D) at 5 degrees. Mean
      change in astigmatism 1 year from baseline was 0.75 D; at 2 years was 1.22 D; and
      at 3 years was 1.68 D. Mean best spectacle-corrected visual acuity (BSCVA) at
      presentation was 20/46 and 20/48 at last follow-up. Eyes requiring surgery
      (23.3%) had mean BSCVA of 20/81 at presentation and 20/106 after surgery. Five
      eyes perforated: 4 spontaneously, and 1 from trauma. Three eyes (6.9%) presented
      with pseudopterygium. Two eyes (4.7%) had intracorneal cysts. Fourteen patients
      (56%) presented with ocular surface inflammation. CONCLUSIONS: Terrien marginal
      degeneration is a slow-progressing, bilateral but asymmetric degeneration of the
      peripheral cornea. Men over 40 are more commonly affected. Stromal thinning,
      vascularization, lipid deposition, and against-the-rule astigmatism are classic
      signs. Though typically noninflammatory, a variant form characterized by
      prominent inflammation exists. Surgery (lamellar graft) can preserve corneal
      integrity and is indicated when conventional options fail to maintain vision or
      if perforation is imminent. Perforations are rare but can result in significant
      vision loss.

PMID- 26210868
TI  - Effect of Different Head Positions in Lateral Decubitus Posture on Intraocular
      Pressure in Treated Patients With Open-Angle Glaucoma.
AB  - PURPOSE: To investigate the effects of different head positions in the lateral
      decubitus posture on intraocular pressure (IOP) in medically treated patients
      with open-angle glaucoma (OAG). DESIGN: Prospective observational study. METHODS:
      setting: Institutional. PARTICIPANTS: Twenty patients with bilateral OAG who
      received only latanoprost as treatment. OBSERVATION PROCEDURES: IOP was measured
      using an ICare Pro tonometer in the sitting, supine, right, and left lateral
      decubitus posture. In lateral decubitus posture, IOP measurements were taken with
      3 different head positions (30 degrees higher than, 30 degrees lower than, and
      parallel to the center of the thoracic vertebra) in a randomized sequence. MAIN
      OUTCOME MEASURES: Comparison of the IOPs between the dependent (lower-sided) and
      nondependent eyes in the lateral decubitus postures with different head
      positions. We also analyzed the differences in IOPs between the better and worse
      eyes. RESULTS: IOP was higher in the dependent eyes than in the nondependent eyes
      in lateral decubitus posture, regardless of the head position (all P < .05).
      Lower head position increased the IOP of dependent eyes, compared with the
      neutral or higher head position. However, the amounts of IOP elevation seen
      during the changes of body posture or head position were not significantly
      different between the better and worse eyes. CONCLUSIONS: Low head position
      elevates IOP of the dependent eyes of medically treated OAG patients compared
      with neutral head position in the lateral decubitus posture. Adjustment of the
      height of a pillow may help mitigate IOP elevations resulting from lying on the
      side with a low or no pillow in glaucoma patients.

PMID- 26210867
TI  - Comparison Between Polymicrobial and Fungal Keratitis: Clinical Features, Risk
      Factors, and Outcome.
AB  - PURPOSE: To compare the clinical features, risk factors, and outcome of
      polymicrobial keratitis with monomicrobial keratitis due to fungus. DESIGN:
      Retrospective, comparative interventional case series. METHODS: Consecutive cases
      of microbial keratitis with significant growth of more than 1 organism in culture
      and culture-proven fungal keratitis treated with natamycin alone were retrieved
      from the microbiology department. Complete success was defined as resolution of
      the infiltrate with scar formation on medical treatment, partial success as
      resolution following tissue adhesive application, and failure as inadequate
      response to medical therapy with increasing infiltrate size, corneal melting,
      and/or perforation necessitating therapeutic penetrating keratoplasty (PKP) or
      evisceration. RESULTS: There were 34 eyes of 34 patients with polymicrobial
      keratitis and 60 cases of fungal keratitis. Compared to patients with fungal
      keratitis, patients with polymicrobial keratitis were significantly older (50.03
      +/- 9.81 years vs 42.79 +/- 12.15 years, P = .0038), with larger infiltrates at
      presentation (61.8% vs 24.1%, P = .0007), a higher association with
      endophthalmitis (11.8% vs 0%, P = .03), previous history of corneal graft (20.6%
      vs 0%, P = .0012), and prior topical corticosteroid use (23.5% vs 5%, P = .019).
      In the polymicrobial group, a combination of bacteria and fungus was more
      frequently isolated (23, 67.6%), among which filamentous fungi (25, 39.1%) and
      coagulase-negative staphylococci (14, 21.9%) comprised a majority. Complete
      success was significantly lower in the polymicrobial group compared to the fungal
      keratitis group (39.3% vs 73.7%, P = .0045). In multivariate logistic regression
      analysis comparing factors affecting the outcome between the 2 groups, older age
      (P = .027) and ulcers larger than 6 mm (P = .001) at presentation adversely
      affected outcome. CONCLUSIONS: Polymicrobial keratitis with fungus and bacteria
      was more common and more challenging to treat, with a poorer outcome than fungal
      keratitis. Medical treatment may be effective; however, therapeutic PKP provided
      globe salvage at best. Early PKP may be advocated for larger ulcers at
      presentation.

PMID- 26210869
TI  - Interventions for Diabetic Retinopathy in Type 1 Diabetes: Systematic Review and
      Meta-Analysis.
AB  - PURPOSE: To systematically review the effectiveness of systemic interventions for
      diabetic retinopathy (DR) in type 1 diabetes. DESIGN: Systematic review and meta
      analysis. METHODS: MEDLINE, EMBASE and Cochrane Library were searched for studies
      published from January 1990 to December 2014. Randomized controlled trials and
      controlled cohort studies reporting incidence or progression of DR following
      systemic intervention were included. Two reviewers selected studies, extracted
      data, and assessed risk of bias. For each intervention, pooled outcomes were
      reported as relative risk (RR) estimates with 95% confidence intervals (CI).
      RESULTS: Twenty-four studies involving 9302 patients met inclusion criteria.
      Incident DR was reduced by intensive vs conventional insulin therapy (RR 0.43;
      95% CI 0.23-0.83), insulin pumps vs multiple daily injections (RR 0.45; 95% CI
      0.24-0.83), and angiotensin receptor blockade vs placebo (RR 0.65; 95% CI 0.49
      0.85). The benefit of insulin pumps over multiple daily infections was
      independent of HbA1c. DR progression was reduced by intensive vs conventional
      insulin therapy (RR 0.63; 95% CI 0.43-0.92), angiotensin-converting enzyme
      inhibition vs placebo (RR 0.60; 95% CI 0.41-0.86), and islet cell transplantation
      vs medical therapy (RR 0.25; 95% CI 0.08-0.71). CONCLUSIONS: Intensive insulin
      therapy, and specifically insulin pump therapy vs multiple daily injections,
      prevents DR in both adults and adolescents with type 1 diabetes. Antihypertensive
      agents provide protection in normotensive, normoalbuminuric adults. In patients
      with type 1 diabetes of longer duration, islet cell transplantation may be more
      effective than medical therapy. There is insufficient evidence for antilipid
      therapy or other systemic interventions.

PMID- 26210870
TI  - Disseminated histoplasmosis mimicking metastatic disease of the colon and
      omentum: Report of a case and literature review.

PMID- 26210871
TI  - An efficient device to experimentally model compression injury of mammalian
      spinal cord.
AB  - We report an efficient and effective device to reproducibly model clinically
      relevant spinal cord injury (SCI) via controlled mechanical compression. In the
      present study, following skin incision, dorsal laminectomy was performed to
      expose T10 spinal cord of adult female Sprague-Dawley rats (230-250 g). The
      vertebral column was suspended and stabilized by Allis clamps at T8 and 12
      spinous processes. A metal impounder was then gently loaded onto T10 dura (20, 35
      or 50 g * 5 min; n=7/group), resulting in acute mild, moderate, or severe
      standing weight compression, respectively. Neurobehavioral outcomes were
      evaluated using the BBB locomotor scale and inclined plane test for coordinated
      hindlimb function, and a battery of spinal reflex tests for sensorimotor
      functions, at 1 day following SCI and weekly thereafter for 7 weeks. Quantitative
      histopathology was used to assess injury-triggered loss of white matter, gray
      matter and ventral horn motor neurons. Immunocytochemical levels of glial
      fibrillary acidic protein (GFAP) and beta-amyloid precursor protein (APP) at the
      cervical and lumbar regions were measured to determine the distal segment impact
      of T10 compression. The data demonstrates that the standardized protocol
      generates weight-dependent hindlimb motosensory deficits and neurodegeneration
      primarily at and near the lesion epicenter. Importantly, there are significantly
      increased GFAP and APP expressions in spinal cord segments involved in eliciting
      post-SCI allodynia. Therefore, the described system reliably produces compression
      trauma in manners partially emulating clinical quasi-static insults to the spinal
      cord, providing a pragmatic model to investigate pathophysiological events and
      potential therapeutics for compression SCI.

PMID- 26210873
TI  - Peroxisome proliferator activated receptor-gamma agonists protect oligodendrocyte
      progenitors against tumor necrosis factor-alpha-induced damage: Effects on
      mitochondrial functions and differentiation.
AB  - The activation of the nuclear receptor peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) is known to exert anti-inflammatory and neuroprotective
      effects and PPAR-gamma agonists are considered potential therapeutic agents in
      brain diseases including those affecting myelin. In demyelinating diseases such
      as multiple sclerosis (MS), inflammation is one of the causes of myelin and
      axonal damage. Oligodendrocyte (OL) differentiation is highly dependent on
      mitochondria, which are major targets of inflammatory insult. Here we show that
      PPAR-gamma agonists protect OL progenitors against the maturational arrest
      induced by the inflammatory cytokine TNF-alpha by affecting mitochondrial
      functions. We demonstrate that the inhibition of OL differentiation by TNF-alpha
      is associated with i) increased mitochondrial superoxide production; ii)
      decreased mitochondrial membrane potential (mMP); and iii) decreased ADP-induced
      Ca(2+) oscillations, which we previously showed to be dependent on efficient
      mitochondria. The TNF-alpha effects were comparable to those of the mitochondrial
      toxin rotenone, further suggesting that TNF-alpha damage is mediated by
      mitochondrial function impairment. PPAR-gamma agonists protected OL progenitors
      against the inhibitory activities of both TNF-alpha and rotenone on mMP,
      mitochondrial ROS production, Ca(2+) oscillations and OL differentiation.
      Finally, the PPAR-gamma agonist pioglitazone increased the expression of PGC
      1alpha (a mitochondrial biogenesis master regulator), UCP2 (a mitochondrial
      protein known to reduce ROS production), and cytochrome oxidase subunit COX1.
      These findings confirm the central role of mitochondria in OL differentiation and
      point to mitochondria as major targets of PPAR-gamma agonist protection against
      TNF-alpha damage. 

PMID- 26210874
TI  - Intrinsic facilitation of adult peripheral nerve regeneration by the Sonic
      hedgehog morphogen.
AB  - Intrinsic molecular determinants of neurodevelopmental outcomes assume new,
      albeit related roles during adult neural regeneration. Here we studied and
      identified a facilitatory role for Sonic hedgehog protein (Shh), a morphogen that
      influences motor neuron floor plate architecture, during adult peripheral neuron
      regeneration. Shh and its receptors were expressed in adult dorsal root ganglia
      (DRG) neurons, axons and glia and trended toward higher levels following axotomy
      injury. Knockdown of Shh in adult sensory neurons resulted in decreased outgrowth
      and branching in vitro, identifying a role for Shh in facilitating outgrowth. The
      findings argued for an intrinsic action to support neuron regeneration. Support
      of advancement and turning however, were not identified in adult sensory neuron
      growth cones in response to local extrinsic gradients of Shh. That intrinsic Shh
      supported the regrowth of peripheral nerves after injury was confirmed by the
      analysis of axon regrowth from the proximal stumps of transected sciatic nerves.
      By exposing regenerating axons to local infusions of Shh siRNA in vivo within a
      conduit bridging the transected proximal and distal stumps, we achieved local
      knockdown of Shh. In response, there was attenuated axonal and Schwann cell
      outgrowth beyond the transection zone. Unlike its role during neurodevelopment,
      Shh facilitates but does not confer regenerative outgrowth properties to adult
      neurons alone. Exploring the differing properties of morphogens and related
      proteins in the adult nervous system identifies new and important roles for them.

PMID- 26210875
TI  - Middle ear muscle reflex measurement in neonates: comparison between 1000Hz and
      226Hz probe tones.
AB  - INTRODUCTION: Middle ear muscle reflex (MEMR) evaluation assists in diagnosing
      hearing problems because normal responses depend on preconditions of a healthy
      auditory system. Studies in neonates recording the acoustic reflex with 226Hz
      probes have described high rates of absence. Other studies using a high frequency
      probe have found higher rates of presence in normal neonates. However, few
      studies have compared results between low and high frequency probes in the same
      newborns. OBJECTIVE: To comparatively assess the ipsilateral acoustic reflex
      recorded by 226Hz and 1000Hz probes in newborns. METHOD: A total of 77 newborns,
      with the presence of transient otoacoustic emissions, underwent tympanometry,
      wideband acoustic immittance, and ipsilateral reflex investigations with 226Hz
      and 1000Hz tone probes. RESULTS: The acoustic reflex was activated at a much
      lower intensity with all activating stimuli using the 1000Hz probe compared with
      the values of the 226Hz probe. There was a higher incidence of ipsilateral
      acoustic reflexes recorded by the 1000Hz tone probe compared to the 226Hz tone
      probe. There was no correlation between the acoustic reflex thresholds and
      otoacoustic emissions. CONCLUSION: In newborns, the acoustic reflex measurements
      obtained with the 1000Hz probe showed advantages over the 226Hz probe.

PMID- 26210872
TI  - The long-term impact of early life pain on adult responses to anxiety and stress:
      Historical perspectives and empirical evidence.
AB  - Approximately 1 in 6 infants are born prematurely each year. Typically, these
      infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they
      experience 10-18 painful and inflammatory procedures each day. Remarkably, pre
      emptive analgesics and/or anesthesia are administered less than 25% of the time.
      Unalleviated pain during the perinatal period is associated with permanent
      decreases in pain sensitivity, blunted cortisol responses and high rates of
      neuropsychiatric disorders. To date, the mechanism(s) by which these long-term
      changes in stress and pain behavior occur, and whether such alterations can be
      prevented by appropriate analgesia at the time of insult, remains unclear. Work
      in our lab using a rodent model of early life pain suggests that inflammatory
      pain experienced on the day of birth blunts adult responses to stress- and pain
      provoking stimuli, and dysregulates the hypothalamic pituitary adrenal (HPA) axis
      in part through a permanent upregulation in central endogenous opioid tone. This
      review focuses on the long-term impact of neonatal inflammatory pain on adult
      anxiety- and stress-related responses, and underlying neuroanatomical changes in
      the context of endogenous pain control and the HPA axis. These two systems are in
      a state of exaggerated developmental plasticity early in postnatal life, and work
      in concert to respond to noxious or aversive stimuli. We present empirical
      evidence from animal and clinical studies, and discuss historical perspectives
      underlying the lack of analgesia/anesthetic use for early life pain in the modern
      NICU.

PMID- 26210876
TI  - [Aeric bubbles developed on the trachea].
AB  - The diverticula of trachea are a frequent observation in thoracic computed
      tomography, in particular in patients presenting an obstructive syndrome. On the
      occasion of a case report of a patient presenting a dilation of bronchi, we
      underline the interest of the post-treatment of the computed tomography
      acquisition, and present a review of the literature on this entity. 

PMID- 26210877
TI  - [Pleural pseudomyxoma: A rare disease].

PMID- 26210878
TI  - [Multidrug-resistant tuberculosis: epidemiology and risk factors].
AB  - Despite the availability of potent drugs and the availability of vaccine,
      tuberculosis remains until today one of the most worrying infectious diseases
      because of both its morbidity and mortality. This serious health problem is
      further complicated by the emergence of multidrug-resistant (MDR) or extensively
      drug-resistant strains (XDR). The number of MDR and XDR strains has continued to
      increase in recent years. Therefore, it is necessary to determine the risk
      factors leading to the emergence of MDR-TB strains to improve its overall
      management. Most studies indicate that the irregular previous treatment of
      tuberculosis with poor adherence is the main risk factor found. Other risk
      factors such as digestive issues, age, sex, and immunosuppression have been
      reported by several studies. In Tunisia, MDR-TB prevalence remains low with 0.8%
      among new cases and 12% among the restatements but control of this disease is
      necessary and remains essentially preventive. It is based on real preventive
      strategies planned according to local and updated regional data.

PMID- 26210879
TI  - [Patient's beliefs about oral targeted therapies and impact on drug adherence in
      lung cancer: A pilot prospective study].
AB  - INTRODUCTION: Oral targeted therapies are a new option for lung cancer treatment.
      However, patient's belief about these drugs - which may interact with adherence -
      is poorly known in this setting. METHOD: Our study is a pilot prospective
      unicentric study. Inclusion criteria were: to have been diagnosed with a lung
      cancer; and to be prescribed with an oral targeted therapy in second line or
      more. The main objective was to assess patient's specific (SB) and general
      beliefs (GB) about these drugs according to the Beliefs about Medicines
      Questionnaire (BMQ). The declared adherence was assessed with the Morisky's test.
      All included patients underwent a semi-structured interview with a psychologist.
      RESULTS: Fifthteen patients were included: 12 underwent erlotinib treatment and 3
      a crizotinib treatment. The mean score (+/-standard deviation) at BMQ was 54/85
      (+/-6) overall; 34/50 (+/-5) for specific belief and 19/35 (+/-3) for general
      belief about drugs. During interview, 47% believed in efficacy of targeted oral
      therapy; 93% reported concerns about their drug; 80% considered that the
      information given by the physician about the drug was comprehensive; but 40%
      still required additional information about it. The mean score at Morisky's test
      was 3/4 (+/-2) and 53% reported to have forgotten at least once their
      antineoplastic drug. No correlation was found between belief and adherence.
      CONCLUSION: Belief about t anti-cancer targeted oral therapy is relatively fair
      but adherence is moderate in this pilot study. Interview shows the need for
      additional information about the prescribed drug.

PMID- 26210880
TI  - [Chryseobacterium indologenes in ventilator-associated pneumonia: First reported
      case in Tunisia].

PMID- 26210881
TI  - Correction of vitamin D deficiency in a cohort of newborn infants using daily 200
      IU vitamin D supplementation.
AB  - INTRODUCTION: Although the role of vitamin D in the prevention of rickets has
      long been well established, controversies still exist on the ideal dose of
      vitamin D supplementation in infants. OBJECTIVE: We assessed serum 25
      hydroxyvitamin D (25OHD) status simultaneously in maternal and cord samples and
      the response to vitamin D3 supplementation in neonates. METHODS: Serum 25OHD
      levels were evaluated from maternal, and umbilical cord samples from term normal
      pregnancies. Repeat 25OHD levels were assessed in neonates with 25OHD below 30
      nmol/L following vitamin D3 200 IU daily after 6 weeks. RESULTS: Blood samples
      were taken including 57 cord samples and 16 follow-up neonatal samples. Maternal
      and cord serum 25OHD were 43 +/- 21 and 29 +/- 15 nmol/L, respectively. Infants
      with 25OHD < 30 nmol/L (19.8 +/- 4.7 nmol/L) had a significant increase in serum
      25OHD (63.3 +/- 14.5 nmol/L) following vitamin D3 200 IU daily after 6 weeks.
      CONCLUSION: Healthy Irish infants born at term are at high risk of vitamin D
      deficiency, but vitamin D3 200 IU daily, rapidly corrects poor vitamin D status.

PMID- 26210882
TI  - Dietary intake of 20 polyphenol subclasses in a cohort of UK women.
AB  - BACKGROUND: Establishing and linking the proposed health benefits of dietary
      polyphenols to their consumption requires measurement of polyphenol intake in
      appropriate samples and an understanding of factors that influence their intake
      in the general population. METHODS: This study examined polyphenol intake
      estimated from 3- and 7-day food diaries in a sample of 246 UK women aged 18-50
      years. Estimation of the intake of 20 polyphenol subclasses commonly present in
      foods consumed by the sample studied was done using Phenol-Explorer((r)) and USDA
      polyphenol databases. Women were participants in the Leeds Women's Wellbeing
      Study (LWW) (n = 143), a dietary intervention study aimed at overweight women
      (mean age 37.2 +/- 9.4 years; mean BMI 30.8 +/- 3.1 kg/m(2)), and the Diet and
      Health Study (DH) (n = 103) which aimed to examine the relationship between
      polyphenol intake and cognitive function (mean age 25.0 +/- 9.0 years; mean BMI
      24.5 +/- 4.6 kg/m(2)). RESULTS: The estimated intake of polyphenol subclasses was
      significantly different between the two samples (p < 0.01) with consumption of
      1292 +/- 844 and 808 +/- 680 mg/day for the LWW and DH groups, respectively.
      Flavanols and hydroxycinnamic acids were the most important contributors to the
      polyphenols consumed by both groups, owing to tea and coffee consumption. Other
      major polyphenol food sources included fruits, vegetables and processed foods.
      CONCLUSION: Older women consumed more polyphenol-containing foods and beverages,
      which was due to the higher coffee and tea consumption amongst the LWW
      participants.

PMID- 26210883
TI  - Effect of genotype, housing system and hay supplementation on carcass traits and
      meat quality of growing rabbits.
AB  - The aim of the study was to examine the effects of genotype (Pannon Large *
      Pannon Ka/Large/or Hungarian Giant * Pannon Ka/Hung), housing system (Cage or
      small Pen) and hay supplementation (Pellet without or with Hay/P+Hay/) on carcass
      and meat (Longissimus dorsi/LD/ and hind leg/HL/) quality of growing rabbits.
      Large rabbits showed higher carcass weights, as well as higher fatness and
      meatiness compared to Hung rabbits. Caged rabbits were heavier, with higher
      prevalence of the mid part of the carcass, and showed higher fatness and lower
      meat toughness than Penned rabbits. Caged rabbits meat was richer in MUFA, but
      poorer in PUFA and Sigma n-6 FA. Hay supplementation impaired carcass weight,
      carcass fatness, L* and a* color, and lipids content. P+Hay increased the HL meat
      content of C18:3 n-6 and C20:5 n-3 FA. Overall results offer further information
      on how alternative breeds, housing systems and feeding strategies can affect
      carcass traits and meat quality.

PMID- 26210884
TI  - How do drivers behave during indecision zone maneuvers?
AB  - Yellow signal indications at intersections are well-known to be a contributor to
      traffic crashes. This study examined drivers' behavior during yellow signal
      indication (i.e., indecision zone) maneuvers. Data from a driving simulator study
      was used, which included drivers' performance data when they encountered a yellow
      signal indication at intersections under different secondary-task conditions.
      This study calculated drivers' likelihood to go through a yellow signal
      indication and examined factors that are related to drivers' decision making on
      intersection traversing. The results showed that drivers' decision on stopping or
      not at a yellow signal indication was associated with different variables
      including age, distraction, pedal conditions, and time to stop line. Distracted
      drivers' insensitive behavior was also captured from the significant interaction
      effect between time to stop line and distraction conditions, which implied that
      intersection related crash risk may increase when drivers were distracted. 

PMID- 26210885
TI  - Pelvic Organ Prolapse in Female Patients Presenting to Transitional Urology Care
      Clinic.
AB  - PURPOSE: Patients with congenital genitourinary abnormalities are growing into
      adulthood and their expectations, especially in the areas of sexual function and
      fertility are creating unforeseen challenges for health care providers. We review
      the incidence and management of pelvic organ prolapse at our Transitional Urology
      Clinic. MATERIALS AND METHODS: This study is a retrospective chart review of the
      presentation and treatment of patients with clinically bothersome pelvic organ
      prolapse seen at our tertiary Transitional Urology Clinic during 2012 to 2015.
      RESULTS: Seven patients with a mean age of 22.8 years presented to our clinic
      with clinically bothersome prolapse. Four patients had myelomeningocele, 2 had
      sacral agenesis and 1 had bladder exstrophy. All were on self-catheterization.
      Three patients were sexually active and 1 had an intact uterus and desired
      fertility. Bothersome symptoms included vaginal bulge in 6 cases, difficult
      vaginal intercourse in 1 and difficult catheterization in 1. For the leading edge
      of Bp (anterior compartment) prolapse the median POP-Q (Pelvic Organ Prolapse
      Quantification System) stage was 3 (range 1 to 3), for Bp (posterior compartment)
      prolapse it was 1 (range 0 to 3) and for C (vaginal vault or cervical) prolapse
      it was 2 (range 1 to 3). Management included pessary in 1 case, hysterectomy with
      bilateral uterosacral ligament suspension in 4, sacrocolpopexy in 1 and
      observation in 1. Mean followup was 17.6 months (range 1 to 92). One of the 5
      patients treated with surgical intervention had recurrence in the anterior
      compartment and vaginal vault. CONCLUSIONS: Females with congenital genitourinary
      anomalies present with pelvic organ prolapse at a much younger age and a more
      advanced stage. There is a paucity of literature on the epidemiology,
      presentation and management of pelvic organ prolapse in this patient population.

PMID- 26210886
TI  - Syndecan-1 alters heparan sulfate composition and signaling pathways in malignant
      mesothelioma.
AB  - Syndecan-1 is a proteoglycan that acts as co-receptor through its heparan sulfate
      (HS) chains and plays important roles in cancer. HS chains are highly variable in
      length and sulfation pattern. This variability is enhanced by the SULF1/2
      enzymes, which remove 6-O-sulfates from HS. We used malignant mesothelioma, an
      aggressive tumor with poor prognosis, as a model and demonstrated that syndecan-1
      over-expression down-regulates SULF1 and alters the HS biosynthetic machinery.
      Biochemical characterization revealed a 2.7-fold reduction in HS content upon
      syndecan-1 over-expression, but an overall increase in sulfation. Consistent with
      low SULF1 levels, trisulfated disaccharides increased 2.5-fold. ERK1/2 activity
      was enhanced 6-fold. Counteracting ERK activation, Akt, WNK1, and c-Jun were
      inhibited. The net effect of these changes manifested in G1 cell cycle arrest.
      Studies of pleural effusions showed that SULF1 levels are lower in pleural
      malignancies compared to benign conditions and inversely correlate with the
      amounts of syndecan-1, suggesting important roles for syndecan-1 and SULF1 in
      malignant mesothelioma. 

PMID- 26210887
TI  - Discontinuing MEK inhibitors in tumor cells with an acquired resistance increases
      migration and invasion.
AB  - BACKGROUND: Development of small molecular inhibitors against BRAF and MEK has
      been a breakthrough in the treatment of malignant melanoma. However, the long
      term effect is foiled in virtually all patients by the emergence of resistant
      tumor cell populations. Therefore, mechanisms resulting in the acquired
      resistance against BRAF and MEK inhibitors have gained much attention and several
      strategies have been proposed to overcome tumor resistance, including interval
      treatment or withdrawal of these compounds after disease progression. METHODS:
      Using a panel of cell lines with an acquired resistance against MEK inhibitors,
      we have evaluated the sensitivity of these cells against compounds targeting
      AKT/mTOR signaling, as well as novel ERK1/2 inhibitors. Furthermore, the effects
      of withdrawal of MEK inhibitor on migration in resistant cell lines were
      analyzed. RESULTS: We demonstrate that withdrawal of BRAF or MEK inhibitors in
      tumor cells with an acquired resistance results in reactivation of ERK1/2
      signaling and upregulation of EMT-inducing transcription factors, leading to a
      highly migratory and invasive phenotype of cancer cells. Furthermore, we show
      that migration in these cells is independent from AKT/mTOR signaling. However,
      combined targeting of AKT/mTOR using MK-2206 and AZD8055 efficiently inhibits
      proliferation in all resistant tumor cell lines analyzed. CONCLUSIONS: We propose
      that combined targeting of MEK/AKT/mTOR or treatment with a novel ERK1/2
      inhibitor downstream of BRAF/MEK suppresses proliferation as well as migration
      and invasion in resistant tumor cells. We provide a rationale against the
      discontinuation of BRAF or MEK inhibitors in patients with an acquired
      resistance, and provide a rationale for combined targeting of AKT/mTOR and
      MEK/ERK1/2, or direct targeting of ERK1/2 as an effective treatment strategy.

PMID- 26210888
TI  - Orexin type 1 receptor antagonism in rat locus coeruleus prevents the analgesic
      effect of intra-LC met-enkephalin microinjection.
AB  - Long-term administration of opiates leads to development of tolerance to
      analgesic effects. This in turn compromise clinical use of these drugs for pain
      management. Although extensive studies have been conducted, the involved cellular
      mechanisms are still poorly understood. The nucleus locus coeruleus (LC), which
      is a dense homogenous cluster of noradrenergic neurons in brainstem, has been
      reported to be involved in mediating opiate effects including analgesia and
      tolerance. LC neurons express a high density of opioid receptors. On the other
      hand, orexinergic neurons send widespread projections to the LC region. Among the
      two types of orexin receptors (OX1R and OX2R), OX1R is highly expressed in LC
      neurons. It has been shown that orexin-A is involved in modulation of nociceptive
      behavior. Also, previous studies have demonstrated the involvement of OX1R in the
      development of morphine induced analgesia and tolerance. In the present study,
      the involvement of OX1R in development of met-enkephalin (ME) analgesic tolerance
      was investigated in LC nucleus. The tail flick test was used to evaluate the
      analgesic effect of intra-LC microinjection of ME in male Wistar rats (250-300g).
      Analgesic responses were reported as the percentage of maximum possible effect (%
      of MPE). Also, SB-334867 was used as a selective OX1R antagonist. Results
      indicate that intra-LC microinjection of ME (5MUg/100nL) results in development
      of analgesic tolerance in 3days. Also, OX1R antagonism in LC nucleus
      significantly prevents the analgesic effect of intra-LC met-enkephalin
      microinjection. It appears that the analgesic effect of ME in LC neurons is
      mediated by orexinergic system. 

PMID- 26210889
TI  - Non-motor symptoms in genetically defined dystonia: Homogenous groups require
      systematic assessment.
AB  - INTRODUCTION: Dystonia is a movement disorder involving sustained or intermittent
      muscle contractions resulting in abnormal movements and postures. Identification
      of disease causing genes has allowed examination of genetically homogenous
      groups. Unlike the motor symptoms, non-motor characteristics are less clearly
      defined, despite their impact on a patient's quality of life. This review aims to
      examine the evidence for non-motor symptoms, addressing cohort size and methods
      of assessment in each study. METHODS: A systematic and standardised search
      strategy was used to identify the published literature relating to psychiatric
      symptoms, cognition, sleep disorders, sensory abnormalities and pain in each of
      the genetically determined dystonias. Studies were divided according to cohort
      size, method of assessment and whether comparison was made to an appropriate
      control group. RESULTS: Ninety-five articles were identified including reported
      clinical histories (n = 42), case reports and smaller case series (n = 12),
      larger case series (n = 23) and case-control cohorts (n = 18). Psychiatric
      symptoms were the most frequently investigated with anxiety, depression and
      Obsessive-Compulsive disorder being most common. Cognitive impairment involved
      either global deficits or isolated difficulties in specific domains. Disturbances
      to sleep were most common in the dopa-responsive dystonias. Sensory testing in
      DYT1 cases identified an intermediate subclinical phenotype. CONCLUSION: Non
      motor symptoms form an integral component of the dystonia phenotype. However,
      future studies should involve a complete assessment of all symptom subtypes in
      order to understand the frequency and gene-specificity of these symptoms. This
      will enable early symptom identification, appropriate clinical management, and
      provide additional outcome measures in future clinical trials.

PMID- 26210890
TI  - Training a system-literate care coordination workforce.
AB  - People with chronic complex conditions continue to experience increasing health
      system fragmentation and poor coordination. To reverse these trends, one solution
      has been an investment in effective models of care coordination that use a care
      coordinator workforce. Care coordinators are not a homogenous workforce - but an
      applied professional role, providing direct and indirect care, and is often
      undertaken by nurses, allied health professionals, social workers or general
      practitioners. In Australia, there is no training curriculum nor courses, nor
      nationally recognised professional quality standards for the care coordinator
      workforce. With the growing complexity and fragmentation of the health care
      system, health system literacy - shared understanding of the roles and
      contributions of the different workforce professions, organisations and systems,
      among patients and indeed the health workforce is required. Efforts to improve
      health system literacy among the health workforce are increasing at a policy,
      practice and research level. However, insufficient evidence exists about what are
      the health system literacy needs of care coordinators, and what is required for
      them to be most effective. Key areas to build a health system literate care
      coordination workforce are presented. Care coordination is more than an optional
      extra, but one of the only ways we are going to be able to provide equitable
      health services for people with chronic complex conditions. People with low
      health literacy require more support with the coordination of their care,
      therefore we need to build a high performing care coordinator workforce that
      upholds professional quality standards, and is health literacy responsive. 

PMID- 26210891
TI  - Treatment of venous thromboembolism in patients with cancer: A network meta
      analysis comparing efficacy and safety of anticoagulants.
AB  - INTRODUCTION: Low-molecular-weight heparin (LMWH) and vitamin K antagonists (VKA)
      are current treatment options for cancer patients suffering from acute venous
      thromboembolism (VTE). The role of direct-acting oral anticoagulants (DOACs) for
      the treatment of VTE in cancer patients, particular in comparison with the
      current standard of care which is LMWH, remains unclear. In this network meta
      analysis, we compared the relative efficacy and safety of LMWH, VKA, and DOAC for
      the treatment of cancer-associated VTE. METHODS: A pre-specified search protocol
      identified 10 randomized controlled trials including 3242 cancer patients.
      Relative risks (RR) of recurrent VTE (efficacy) and major bleeding (safety) were
      analyzed using a random-effects meta-regression model. RESULTS: LMWH emerged as
      significantly superior to VKA with respect to risk reduction of recurrent VTE
      (RR=0.60, 95%CI:0.45-0.79, p<0.001), and its safety was comparable to VKA
      (RR=1.08, 95%CI:0.70-1.66, p=0.74). For the DOAC vs. VKA efficacy and safety
      comparison, the relative risk estimates were in favor of DOAC, but had confidence
      intervals that still included equivalence (RR for recurrent VTE=0.65, 95%CI:0.38
      1.09, p=0.10; RR for major bleeding=0.72, 95%CI:0.39-1.37, p=0.32). In the
      indirect network comparison between DOAC and LMWH, the results indicated
      comparable efficacy (RR=1.08, 95%CI:0.59-1.95, p=0.81), and a non-significant
      relative risk towards improved safety with DOAC (RR=0.67, 95%CI:0.31-1.46,
      p=0.31). The results prevailed after adjusting for different risk of recurrent
      VTE and major bleeding between LMWH vs. VKA and DOAC vs. VKA studies. CONCLUSION:
      The efficacy and safety of LMWH and DOACs for the treatment of VTE in cancer
      patients may be comparable. FUNDING: Austrian Science Fund (FWF-SFB-54).

PMID- 26210892
TI  - In vitro anti-platelet potency of ticagrelor in blood samples from infants and
      children.
AB  - INTRODUCTION: Ticagrelor, a novel platelet inhibitor acting on the ADP-dependent
      P2Y12 receptor, is currently approved for treating adults with acute coronary
      syndrome. The effect of ticagrelor in children has not been explored. As a first
      step, we here evaluate if the in vitro anti-platelet potency of ticagrelor in
      blood samples from children of different age is different as compared with in
      blood samples from adults. MATERIALS AND METHODS: Blood samples from 36 healthy
      children grouped by age (0-2 months, n=6; 2-6 months, n=6; 6months-2years, n=6; 2
      6 years, n=10; 6-12 years, n=8) and 13 adults were collected for in vitro
      analysis using vasodilator stimulated phosphoprotein phosphorylation (VASP) assay
      in whole blood and ADP-induced light transmission aggregometry (LTA) in platelet
      rich plasma. Ticagrelor (0.01 - 10MUmol/L) was added in vitro and its potency was
      assessed by calculating the concentration that provided 50% inhibition of the
      maximum response (IC50). RESULTS: The in vitro potency of ticagrelor in blood
      from adults and in blood from children of any age group were comparable, both
      when analyzed with LTA and with VASP. CONCLUSIONS: These in vitro results are
      consistent with the hypothesis that ticagrelor would achieve a comparable anti
      platelet effect in children of different ages as in adults at equal plasma
      exposure.

PMID- 26210893
TI  - Re: Jens Sonksen, Neil J. Barber, Mark J. Speakman, et al. Prospective,
      Randomized, Multinational Study of Prostatic Urethral Lift Versus Transurethral
      Resection of the Prostate: 12-month Results from the BPH6 Study. Eur Urol
      2015;68:643-52.

PMID- 26210894
TI  - EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and
      Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1
      Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus
      Calmette-Guerin.
AB  - BACKGROUND: There are no prognostic factor publications on stage Ta-T1 non-muscle
      invasive bladder cancer (NMIBC) treated with 1-3 yr of maintenance bacillus
      Calmette-Guerin (BCG). OBJECTIVE: To determine prognostic factors in NMIBC
      patients treated with 1-3 yr of BCG after transurethral resection of the bladder
      (TURB), to derive nomograms and risk groups, and to identify high-risk patients
      who should be considered for early cystectomy. DESIGN, SETTING, AND PARTICIPANTS:
      Data for 1812 patients were merged from two European Organization for Research
      and Treatment of Cancer randomized phase 3 trials in intermediate- and high-risk
      NMIBC. INTERVENTION: Patients received 1-3 yr of maintenance BCG after TURB and
      induction BCG. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prognostic factors
      for risk of early recurrence and times to late recurrence, progression, and death
      were identified in a training data set using multivariable models and applied to
      a validation data set. RESULTS AND LIMITATIONS: With a median follow-up of 7.4
      yr, 762 patients recurred; 173 progressed; and 520 died, 83 due to bladder cancer
      (BCa). Statistically significant prognostic factors identified by multivariable
      analyses were prior recurrence rate and number of tumors for recurrence, and
      tumor stage and grade for progression and death due to BCa. T1G3 patients do
      poorly, with 1- and 5-yr disease-progression rates of 11.4% and 19.8%,
      respectively, and 1- and 5-yr disease-specific death rates of 4.8% and 11.3%.
      Limitations include lack of repeat transurethral resection in high-risk patients
      and exclusion of patients with carcinoma in situ. CONCLUSIONS: NMIBC patients
      treated with 1-3 yr of maintenance BCG have a heterogeneous prognosis. Patients
      at high risk of recurrence and/or progression do poorly on currently recommended
      maintenance schedules. Alternative treatments are urgently required. PATIENT
      SUMMARY: Non-muscle-invasive bladder cancer patients at high risk of recurrence
      and/or progression do poorly on currently recommended bacillus Calmette-Guerin
      maintenance schedules, and alternative treatments are urgently required. TRIAL
      REGISTRATION: Study 30911 was registered with the US National Cancer Institute
      clinical trials database (protocol ID: EORTC 30911). Study 30962 was registered
      at ClinicalTrials.gov, number NCT00002990;
      http://clinicaltrials.gov/ct2/show/record/NCT00002990.

PMID- 26210896
TI  - Environmental protection from allergic diseases: From humans to mice and back.
AB  - Allergic diseases have a strong environmental component, illustrated by the rapid
      rise of their prevalence in the Western world. Environmental exposures have been
      consistently shown to either promote or protect against allergic disease. Here we
      focus on protective exposures and the pathways they regulate. Traditional
      farming, natural environments with high biodiversity, and pets in the home
      (particularly dogs) have the most potent and consistent allergy-protective
      effects and are actively investigated to identify the environmental and host
      based factors that confer allergy protection. Recent work emphasizes the critical
      protective role of microbial diversity and its interactions with the gut/lung and
      skin/lung axes-a cross-talk through which microbial exposure in the gut or skin
      powerfully influences immune responses in the lung. 

PMID- 26210895
TI  - Testing the 'toxin hypothesis of allergy': mast cells, IgE, and innate and
      acquired immune responses to venoms.
AB  - Work in mice indicates that innate functions of mast cells, particularly
      degradation of venom toxins by mast cell-derived proteases, can enhance
      resistance to certain arthropod or reptile venoms. Recent reports indicate that
      acquired Th2 immune responses associated with the production of IgE antibodies,
      induced by Russell's viper venom or honeybee venom, or by a component of honeybee
      venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to
      challenge with potentially lethal doses of either of the venoms or bvPLA2. These
      findings support the conclusion that, in contrast to the detrimental effects
      associated with allergic type 2 (Th2) immune responses, mast cells and IgE
      dependent immune responses to venoms can contribute to innate and adaptive
      resistance to venom-induced pathology and mortality. 

PMID- 26210897
TI  - Danger signals in stroke.
AB  - Danger molecules are the first signals released from dying tissue after stroke.
      These danger signals bind to receptors on immune cells that will result in their
      activation and the release of inflammatory and neurotoxic mediators, resulting in
      amplification of the immune response and subsequent enlargement of the damaged
      brain volume. The release of danger signals is a central event that leads to a
      multitude of signals and cascades in the affected and neighbouring tissue,
      therefore providing a potential target for therapy. 

PMID- 26210898
TI  - Hardware System for Real-Time EMG Signal Acquisition and Separation Processing
      during Electrical Stimulation.
AB  - The study aimed to develop a real-time electromyography (EMG) signal acquiring
      and processing device that can acquire signal during electrical stimulation.
      Since electrical stimulation output can affect EMG signal acquisition, to
      integrate the two elements into one system, EMG signal transmitting and
      processing method has to be modified. The whole system was designed in a user
      friendly and flexible manner. For EMG signal processing, the system applied
      Altera Field Programmable Gate Array (FPGA) as the core to instantly process real
      time hybrid EMG signal and output the isolated signal in a highly efficient way.
      The system used the power spectral density to evaluate the accuracy of signal
      processing, and the cross correlation showed that the delay of real-time
      processing was only 250 MUs. 

PMID- 26210900
TI  - Development of a Novel Allele-Specific PCR Method for Rapid Assessment of Nervous
      Necrosis Virus Genotypes.
AB  - Viral nervous necrosis infections are causing severe problems on aquaculture
      industry due to ecological and economic impacts. Their causal agent is nervous
      necrosis virus or nodavirus, which has been classified into four genotypes.
      Different genotypes correlate with differences in viral pathogenicity. Therefore,
      rational development of effective vaccines and diagnostic reagents requires
      analysis of the genetic variation. The development and validation of a polymerase
      chain reaction amplification (PCR)-based methodology for nodavirus genotype
      assessment in a simple and robust format is described. Degenerate external
      primers and two genotype-specific internal primers were utilized for simultaneous
      amplification of nodavirus products in a single PCR. A first set of cycles
      produced a long PCR product, defined by the outer primers, and the internal
      primers amplified short DNA fragments specific for each genotype in lower
      annealing temperature. Detection was based on the size of the short products.
      Nodavirus infected and healthy samples were analyzed and none of the non-infected
      samples showed any bands, while all infected samples were positive. The proposed
      method can be performed within 4 h and consumes standard PCR and electrophoresis
      reagents, with costs lower than 2? per sample. Tetra-primer PCR is a suitable
      alternative for virus sequencing in medium scale research laboratories and
      farming facilities.

PMID- 26210899
TI  - The Challenges of Prevention, Diagnosis and Treatment of Ischemic Heart Disease
      in Women.
AB  - Increasing evidence suggests that there are significant differences in the
      presentation, diagnosis and treatment of ischemic heart disease in women compared
      to men. Women often present with atypical symptoms, and this, in association with
      a consistent underestimation of their risk for ischemic heart disease, leads to
      underdiagnosis and undertreatment in women. Cardiovascular risk factors unique to
      women have only recently been recognized, and moreover, traditional risk factors
      have recently been shown to have greater impacts on women. Consequently, women
      suffer more disability and poorer clinical outcomes, with higher cardiovascular
      morbidity and mortality. These discrepancies may in part be secondary to the
      higher prevalence of nonobstructive coronary artery disease in women with
      persistent chest pain symptoms as compared to men when evaluated invasively.
      Focused diagnostic and therapeutic strategies unique to women are thus needed,
      but unfortunately, such sex-specific guidelines do not yet exist, largely due to
      lack of awareness, both on the part of providers and patients, as well as a
      paucity of evidence-based research specific to women. Although underutilized in
      women, diagnostic modalities, including functional and anatomic cardiac tests as
      well as physiologic assessments of endothelial and microvascular function, are
      useful for establishing the diagnosis and prognosis of suspected ischemic heart
      disease in women. This review discusses the current challenges of prevention,
      diagnosis and treatment of ischemic heart disease in women. 

PMID- 26210901
TI  - Removal of Rotavirus and Bacteriophages by Membrane Bioreactor Technology from
      Sewage.
AB  - Human enteric viruses constitute a public health concern due to their low
      infectious dose and their resistance to environmental factors and to inactivation
      processes. We aimed at assessing the performance of a laboratory scale Submerged
      membrane bioreactor (SMBR) treating abattoir wastewaters for Rotavirus (RV) and
      total coliphages removal. We also aimed at evaluating removal efficiency of
      enteric viruses through conventional activated sludge treatment by measuring
      concentrations of total coliphages, considered as fecal and viral contamination
      indicators, with double-layer agar technique. The Log10 reduction values of
      bacteriophages ranged from 1.06 to 1.47. Effluents were analyzed to investigate
      and quantify RV, hepatitis A virus (HAV), Hepatitis E virus (HEV), Noroviruses
      genogroup I (NoV GI) and genogroup II (NoVGII), and Enterovirus (EV) by real-time
      PCR, using standardized detection kits (ceeramTools detection kits((r))). All
      effluent samples were positive for RV; concentrations ranged from 5.2 * 10(5) to
      1.3 * 10(7) genome copies/L. These results highlight the inefficiency of
      conventional biological process for viral removal. A complete removal of RV
      during Membrane Bioreactor treatment was obtained. To the best of our knowledge,
      this is the first study providing an evidence of removal of RV simultaneously
      with total coliphages by SMBR.

PMID- 26210902
TI  - Isolation and Identification of Arcobacter spp. by Multiplex PCR from Water
      Sources in Kars Region.
AB  - This study was conducted to determine the prevalence of Arcobacter spp. in
      various water sources of stream, creek, pond, and drinking water in Kars and
      surrounding areas. A total of 113 water samples including 19 samples from creeks,
      49 from streams, 10 from ponds, and 35 from drinking water samples collected from
      different regions were examined for presence of Arcobacter spp. by cultural
      methods. Arcobacter spp. were isolated from 14 (12.38 %) samples including 5
      (26.31 %) creek and 9 (18.36 %) stream water samples and all were identified as
      Arcobacter butzleri by multiplex PCR. No agent was isolated from pond and
      drinking water samples. The results of this study demonstrated that creek and
      stream waters are contaminated by this agent showing high potential risk of
      Arcobacter species to be transmitted to humans and animals and in the
      contamination of food. It is concluded that water sources should also be
      considered as a factor not only carrying agents but also as a primary source of
      the infection.

PMID- 26210903
TI  - The optimization of peripheral nerve recovery using cortical reorganization
      techniques: A retrospective study of wrist level nerve repairs.
AB  - STUDY DESIGN: Retrospective case series. INTRODUCTION: Outcomes following
      peripheral nerve repairs have not significantly improved over the past few
      decades. A new protocol using cortical reorganization techniques was developed
      with the goal of improving nerve recovery in the hand. PURPOSE OF THE STUDY: To
      determine if early sensory re-education using cortical reorganization techniques
      improved sensory outcomes in the hand after repair of wrist-level nerve injuries.
      METHODS: A retrospective study was completed of wrist-level peripheral nerve
      repairs in patients who underwent a sensory re-education protocol which included
      cutaneous anesthesia, tactile stimulation, and sensory and motor imagery. Data
      for static 2-point discrimination, Semmes Weinstein monofilament assessments and
      the shortened version of the Disabilities of the Arm, Shoulder and Hand
      (QuickDASH) scores were collected. RESULTS: At four months post-repair, three of
      seven of the median nerve lacerations had static 2-point discrimination of 7 mm
      or less in at least one digit. Using the Semmes Weinstein monofilaments, 9 of 11
      nerve repairs felt the 4.31 filament (protective) or better by eleven months with
      five able to perceive the 2.83 filament (normal) in that time frame. CONCLUSIONS:
      This limited retrospective study suggests that early sensory re-education using
      cortical reorganization techniques may improve sensory outcomes. A larger scale
      study is indicated to confirm our findings. LEVEL OF EVIDENCE: IV.

PMID- 26210904
TI  - Cross-cultural adaptation and psychometric testing of the Arabic version of the
      Patient-Rated Wrist Hand Evaluation (PRWHE-A) in Saudi Arabia.
AB  - PURPOSES: The purposes of this study was to 1) perform a cross-cultural Arabic
      translation for the Patient-Rated Wrist and Hand Evaluation (PRWHE-A) using
      standardized guidelines and, 2) to test the psychometrics properties of the
      translated measure. METHODS: A total of 48 patients with variety of hand
      disabilities, a mean age of 47 +/- 16 years were recruited and assessed two
      times. The intraclass correlation coefficient (ICC) was used for assessing test
      retest reliability of the PRWHE-A and its subscales while Cronbach's alpha (CA)
      was used for assessing the internal consistency. Construct validity was assessed
      by examining the strength of the correlation between the PRWHE-A and the Arabic
      version of the Disability of the Arm, Shoulder and Hand (DASH-A). RESULTS: The
      PRWHE-A demonstrated excellent test-retest reliability (ICC= 0.97) and internal
      consistency (CA= 0.96). The DASH-A demonstrated moderately to low correlation (r=
      0.64) with the PRWHE-A. CONCLUSIONS: The results of this study indicated that
      PRWHE-A is a reliable and valid assessment tool and can be used in patients with
      different wrist/hand disabilities whose primary language is Arabic.

PMID- 26210905
TI  - Chronic joint pain in the lower body is associated with gait differences
      independent from radiographic osteoarthritis.
AB  - Gait is an important indicator of health. Chronic lower body pain may impair gait
      and lead to morbidity and mortality. We investigated the associations between
      lower body pain and gait in community-dwelling individuals, independent from
      osteoarthritis (OA). This population based cohort study included 2304 Rotterdam
      Study participants who underwent electronic walkway gait assessment. Thirty
      different variables resulting from gait assessment were summarized into seven
      gait domains using principle components analysis: i.e. Rhythm, Variability,
      Phases, Pace, Tandem, Turning, and Base of Support. Chronic lower body pain was
      assessed using pain drawings. OA was defined as a Kellgren & Lawrence score of 2
      or higher on radiographs of the hip and/or knee. Linear regression analysis was
      used to study associations. Participants with chronic pain in the leg and hip,
      had lower Rhythm, Phases, and Pace, independent from OA. Additionally, we found
      unilateral pain to associate with larger gait asymmetry. No associations were
      found between chronic pain and the other gait domains, including gait
      variability. However, within individuals with hip pain, gait variability was
      higher in individuals with radiographic OA compared to those without OA. This is
      the first population based study showing chronic lower body pain associates with
      gait differences independent from OA. Participants with pain were found to walk
      with slower and smaller steps, longer double support and more asymmetry. Proper
      care and treatment of chronic pain could be a way of reducing gait problems and
      thereby fall risk and associated mortality. In addition, gait assessment may help
      identifying individuals with OA from those having pain due to other causes. 

PMID- 26210906
TI  - Human adipose-derived mesenchymal stem cells attenuate collagen antibody-induced
      autoimmune arthritis by inducing expression of FCGIIB receptors.
AB  - BACKGROUND: Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs)
      derived from adipose tissue. MSCs have multiple properties including anti
      inflammatory and immunomodulatory effects in various disease models and human
      diseases. However, the mechanisms underlying this wide range of effects need to
      be explored. METHODS: Collagen antibody-induced arthritis (CAIA) is a unique
      model in which arthritis is rapidly and strongly induced. ASCs were
      intraperitoneally infused into CAIA mice before or after arthritis induction. The
      serum levels of various cytokines, adipokines, and chemokines were measured. The
      expression of FC gamma receptors (FCGRs) was investigated in peritoneal
      macrophages ex vivo. RAW264.7 cells and ASCs were co-cultured to elucidate the
      direct and indirect role of ASCs on FCGR expression. RESULTS: ASCs attenuated
      arthritis in CAIA mice. Serum levels of tumor necrosis factor alpha, interleukin
      (IL)-15, resistin, and leptin were reduced in ASC-treated CAIA mice, whereas
      serum levels of IL-6 and adiponectin were not affected. In peritoneal macrophages
      isolated from ASC-treated mice, expression of FCGRIIB, which is immunoinhibitory,
      was higher than that of FCGRI. Co-culture of ASCs with RAW264.7 cells modulated
      the expression of FCGRs. The expression patterns and timings of peak expression
      differed among FCGRs. Expression of FCGRIIB was higher and peaked earlier than
      that of FCGRI. FCGRIII expression was not affected by this co-culture.
      CONCLUSIONS: This is a study to show that ASCs have anti-arthritic effects in
      CAIA mice. Modulation of FCGRs by ASCs might be a therapeutic mechanism in this
      antibody-associated arthritis model.

PMID- 26210907
TI  - Emergence times and airway reactions in general laryngeal mask airway anesthesia:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: The use of a laryngeal mask airway (LMA) in appropriate patients
      supports fast-track anesthesia with a lower incidence of postoperative airway
      connected adverse events. Data on the most favorable anesthetic in this context,
      with the lowest rate of upper airway complications and fast emergence times, are
      controversial and limited. Desflurane seems to match these criteria best, but
      large randomized controlled trials (RCTs) with a standardized study protocol are
      lacking. Therefore, we aim to compare desflurane with other commonly used
      anesthetics, sevoflurane and propofol, in a sufficiently powered RCT. We
      hypothesize that desflurane is noninferior regarding the frequency of upper
      airway events and superior regarding the emergence times to sevoflurane and
      propofol. METHODS/DESIGN: A total of 351 patients undergoing surgery with an LMA
      will be included in this prospective, randomized, double-blind controlled,
      multicenter clinical trial. The patients will be randomly assigned to the three
      treatment arms: desflurane (n = 117), sevoflurane (n = 117), and propofol (n =
      117). The emergence time (time to state the date of birth) will be the primary
      endpoint of this study. The secondary endpoints include further emergence times,
      such as time to open eyes, to remove LMA, to respond to command and to state
      name. Additionally, we will determine the frequency of cough and laryngospasm,
      measured intraoperatively and at emergence. We will assess the postoperative
      recovery on the first postoperative day via the Postoperative Quality Recovery
      Scale. DISCUSSION: Despite increasing importance of cost-effective and safe
      anesthesia application, we lack proof for the most advantageous anesthetic agent,
      when an LMA is used. There are only a few RCTs comparing desflurane to other
      commonly used anesthetics (sevoflurane, propofol and isoflurane) in patients with
      LMA. These RCTs were conducted with small sample sizes, huge interstudy
      variability, and some also showed strong biases. The present multicenter RCT will
      provide results from a large sample size with a standardized study protocol and
      minimized bias, which is feasible in the clinical routine. Furthermore, we will
      expand our knowledge regarding the most favorable recovery on the first
      postoperative day, which impacts patients' comfort after surgery. TRIAL
      REGISTRATION: EudraCT Identifier: 2014-003810-96, 5 September 2014
      ClinicalTrials.gov: NCT02322502, December 2014.

PMID- 26210908
TI  - Secondhand Smoke Exposure Reduction After NICU Discharge: Results of a Randomized
      Trial.
AB  - OBJECTIVE: Premature infants are at high risk for respiratory disease, and
      secondhand smoke (SHS) exposure further increases their risk for developing
      respiratory illness and asthma. Yet, SHS exposure remains problematic in this
      vulnerable population. Our objective was to evaluate the effects of brief asthma
      education plus motivational interviewing counseling on reducing SHS exposure and
      improving respiratory outcomes in premature infants compared to asthma education
      alone. METHODS: Caregivers and their infants <=32 weeks' gestational age were
      enrolled after discharge from a neonatal intensive care unit in Rochester, New
      York, from 2007 to 2011. Participants (N = 165, 61% Medicaid insurance, 35%
      Black, 19% Hispanic, 59% male) were stratified by infant SHS exposure and
      randomly assigned to treatment or comparison groups. RESULTS: Caregivers in the
      treatment group reported significantly more home smoking bans (96% vs 84%, P =
      .03) and reduced infant contact with smokers after the intervention (40% vs 58%,
      P = .03), but these differences did not persist long term. At study end (8 months
      after neonatal intensive care unit discharge), treatment group infants showed
      significantly greater reduction in salivary cotinine versus comparison (-1.32
      ng/mL vs -1.08 ng/mL, P = .04), but no significant differences in other clinical
      outcomes. CONCLUSIONS: A community-based intervention incorporating motivational
      interviewing and asthma education may be helpful in reducing SHS exposure of
      premature infants in the short term. Further efforts are needed to support
      sustained protections for this high-risk group and ultimately, prevent acute and
      chronic respiratory morbidity. Strategies for successfully engaging families
      during this stressful period warrant attention.

PMID- 26210909
TI  - Accuracy of Weight Perceptions in a Nationally Representative Cohort of US 8th
      Grade Adolescents.
AB  - OBJECTIVE: To describe the accuracy of weight perceptions in a nationally
      representative sample of US 8th graders, its relationship with weight control
      intentions (WCI), and the relationship of weight misperceptions and WCI with diet
      and activity behaviors. METHODS: Data analyzed came from the 8th grade wave (2006
      2007) of the Early Childhood Longitudinal Study-Kindergarten Class, a nationally
      representative sample. Body mass index was calculated from height and weight
      measurements for 7800 8th graders (mean age 14.3 years). Measured weight status
      was categorized into underweight, normal weight, overweight, and obese using the
      US Centers for Disease Control and Prevention's age- and sex-specific growth
      charts. Self-reported weight status was compared with measured weight status to
      classify adolescents into accurate perceivers, overestimators, and
      underestimators. Multivariate logistic and negative binomial regression models
      were estimated for binary and count data outcome variables, respectively.
      RESULTS: Overall, 42.1% of adolescents misperceived their weight status: 35.3%
      underestimated and 6.8% overestimated their weight status. Among overweight or
      obese adolescents, 68.4% misperceived their weight status; 35% of underweight
      adolescents overestimated their weight status. Among normal-weight adolescents,
      8.5% overestimated and 18.5% underestimated their weight. Compared to accurate
      perception, both overestimation and underestimation of weight status were
      associated with greater likelihood of inappropriate WCI, but only underestimation
      was associated with unhealthy diet and activity behaviors. CONCLUSIONS: Weight
      misperception was a common problem among US adolescents from all weight
      categories and was associated with inappropriate WCI. Future research should
      examine how adolescents' weight perceptions are formed and whether reducing
      misperceptions may improve behaviors.

PMID- 26210910
TI  - Non-medical use of psychoactive drugs in relation to suicide tendencies among
      Chinese adolescents.
AB  - INTRODUCTION: To investigate the prevalence of non-medical use of psychoactive
      prescription drug (NMUPD) among adolescents and to explore the associations
      between non-medical psychoactive prescription drug use and depressive symptoms,
      poor sleep quality, deliberate self-harm, and suicide. METHODS: A two-stage
      stratified cluster sample design produced a representative sample of 12-19-year
      old students in grades 1-6 who attended public middle schools in Guangdong
      province. Prevalence estimates (SE) of non-medical psychoactive prescription drug
      use were calculated, and logistic regression was used to examine its association
      with depressive symptoms, poor sleep quality, deliberate self-harm, and suicide.
      RESULTS: Overall, 7.5% of adolescents reported non-medical use of opioids, and
      4.8% of adolescents reported non-medical use of sedatives. Lifetime, last-year,
      and last-month non-medical use of opioids and sedatives were positively
      associated with depressive symptoms, poor sleep quality, deliberate self-harm,
      suicidal ideation, and suicidal attempts among different gender and age-group
      adolescents. Those who reported last month non-medical use of opioids and
      sedatives had the greatest odds of reporting depressive symptoms, poor sleep
      quality, deliberate self-harm, suicidal ideation, and suicidal attempts. Males
      who were last month non-medical users of opioids or sedative had 8.9 or 10.7
      times greater odds of reporting a suicidal attempt, and 8.8 or 9.8 times greater
      odds of reporting a suicidal attempt were observed among adolescents aged 16-19
      who were last-month non-medical users of opioids or sedatives. CONCLUSIONS: These
      findings provide evidence for improving adolescents' suicide prevention strategy
      by targeting supervision on high risk current non-medical users of psychoactive
      drug.

PMID- 26210911
TI  - Can we predict retention in longitudinal studies of substance use? Findings from
      the Australian Treatment Outcome Study.
AB  - BACKGROUND: Longitudinal studies are often threatened by difficulties with sample
      attrition, high rates of which threaten the validity of study findings. The
      present study examined methodological and participant characteristics associated
      with sample retention in the Australian Treatment Outcome Study (ATOS) across
      3years. METHOD: Follow-up interviews were conducted at 3-, 12-, 24-, and 36
      months post baseline, with follow-up rates of 89%, 81%, 76% and 70%,
      respectively. Structured interviews measuring past-month drug use, mental health,
      criminal involvement and demographic characteristics were administered to
      participants at baseline and each follow-up. Data were analysed using multinomial
      logistic regression and generalised estimating equations to produce odds ratios
      with 95% confidence intervals. RESULTS: Completing all follow-up interviews was
      associated with being in treatment (OR 3.62), using other opiates at baseline (OR
      3.45), more years of schooling (OR 1.20), and having completed the previous
      interview (OR 35.04). A history of incarceration was independently associated
      with not completing follow-up interviews (OR 0.47). CONCLUSION: Retention can
      largely be predicted at study entry, and is unaffected by changes that occur in
      the interim. These findings highlight the importance of obtaining and maintaining
      comprehensive locator information, maintaining strong relationships with
      treatment agencies, as well as the necessity of patience, perseverance and
      flexibility.

PMID- 26210912
TI  - DRESS syndrome: cerebral vasculitic-like presentation.
AB  - INTRODUCTION: DRESS (drug reaction with eosinophilia and systemic symptoms)
      syndrome is a severe adverse drug-induced reaction. It manifests with pyrexia,
      eosinophilia, and lymphadenopathy, with multiple organ involvement, mainly the
      skin, liver, and kidneys. The purpose of this article is to demonstrate that
      DRESS syndrome can be associated with cerebral manifestations, a concept not well
      known in the neuroradiological literature. METHODS: We describe three cases of
      DRESS syndrome associated with cerebral vasculitic-like lesions and realize a
      review of the literature to demonstrate that this association represents a very
      rare entity. RESULTS: Acute ischemic lesions were found among two patients. In
      all cases, perivascular enhancement was present. Magnetic resonance angiography
      (MRA) sequence was normal. Although no cerebral biopsy was performed, this
      enhancement pattern is strongly suggestive of a vasculitic process associated
      with DRESS syndrome. CONCLUSION: Diagnosis of cerebral vasculitic-like associated
      lesions must be considered in patients with DRESS syndrome since it can be
      reversed completely by withdrawing the causal medication and instigating
      corticosteroid treatment in a timely fashion.

PMID- 26210914
TI  - Weighting training images by maximizing distribution similarity for supervised
      segmentation across scanners.
AB  - Many automatic segmentation methods are based on supervised machine learning.
      Such methods have proven to perform well, on the condition that they are trained
      on a sufficiently large manually labeled training set that is representative of
      the images to segment. However, due to differences between scanners, scanning
      parameters, and patients such a training set may be difficult to obtain. We
      present a transfer-learning approach to segmentation by multi-feature voxelwise
      classification. The presented method can be trained using a heterogeneous set of
      training images that may be obtained with different scanners than the target
      image. In our approach each training image is given a weight based on the
      distribution of its voxels in the feature space. These image weights are chosen
      as to minimize the difference between the weighted probability density function
      (PDF) of the voxels of the training images and the PDF of the voxels of the
      target image. The voxels and weights of the training images are then used to
      train a weighted classifier. We tested our method on three segmentation tasks:
      brain-tissue segmentation, skull stripping, and white-matter-lesion segmentation.
      For all three applications, the proposed weighted classifier significantly
      outperformed an unweighted classifier on all training images, reducing
      classification errors by up to 42%. For brain-tissue segmentation and skull
      stripping our method even significantly outperformed the traditional approach of
      training on representative training images from the same study as the target
      image. 

PMID- 26210913
TI  - Interpreting support vector machine models for multivariate group wise analysis
      in neuroimaging.
AB  - Machine learning based classification algorithms like support vector machines
      (SVMs) have shown great promise for turning a high dimensional neuroimaging data
      into clinically useful decision criteria. However, tracing imaging based patterns
      that contribute significantly to classifier decisions remains an open problem.
      This is an issue of critical importance in imaging studies seeking to determine
      which anatomical or physiological imaging features contribute to the classifier's
      decision, thereby allowing users to critically evaluate the findings of such
      machine learning methods and to understand disease mechanisms. The majority of
      published work addresses the question of statistical inference for support vector
      classification using permutation tests based on SVM weight vectors. Such
      permutation testing ignores the SVM margin, which is critical in SVM theory. In
      this work we emphasize the use of a statistic that explicitly accounts for the
      SVM margin and show that the null distributions associated with this statistic
      are asymptotically normal. Further, our experiments show that this statistic is a
      lot less conservative as compared to weight based permutation tests and yet
      specific enough to tease out multivariate patterns in the data. Thus, we can
      better understand the multivariate patterns that the SVM uses for neuroimaging
      based classification. 

PMID- 26210916
TI  - Hematite and hematite-akageneite composites. XRD and electrokinetic study and
      interaction with ionic surfactants.
AB  - Hematite and hematite-akageneite composites were obtained by hydrolysis of FeCl3
      in acidic medium. The IEP of hematite and of hematite-akageneite composites was
      at pH about 9. The particle radius of primary hematite particles was about 50nm
      and the primary particles of hematite-akageneite composites were larger and
      porous. Addition of SDS to dispersions containing hematite or hematite-akageneite
      composites resulted in substantial increase in the particle size. 

PMID- 26210915
TI  - Cardiovascular imaging in children and adults following Kawasaki disease.
AB  - Kawasaki disease (KD) is a paediatric vasculitis with coronary artery aneurysms
      (CAA) as its main complication. Two guidelines exist regarding the follow-up of
      patients after KD, by the American Heart Association and the Japanese Circulation
      Society. After the acute phase, CAA-negative patients are checked for
      cardiovascular risk assessment or with ECG and echocardiography until 5 years
      after the disease. In CAA-positive patients, monitoring includes myocardial
      perfusion imaging, conventional angiography and CT-angiography. However, the
      invasive nature and high radiation exposure do not reflect technical advances in
      cardiovascular imaging. Newer techniques, such as cardiac MRI, are mentioned but
      not directly implemented in the follow-up. Cardiac MRI can be performed to
      identify CAA, but also evaluate functional abnormalities, ischemia and previous
      myocardial infarction including adenosine stress-testing. Low-dose CT angiography
      can be implemented at a young age when MRI without anaesthesia is not feasible.
      CT calcium scoring with a very low radiation dose can be useful in risk
      stratification years after the disease. By incorporating newer imaging
      techniques, detection of CAA will be improved while reducing radiation burden and
      potential complications of invasive imaging modalities. Based on the current
      knowledge, a possible pathway to follow-up patients after KD is introduced. Key
      Points * Kawasaki disease is a paediatric vasculitis with coronary aneurysms as
      major complication. * Current guidelines include invasive, high-radiation
      modalities not reflecting new technical advances. * Cardiac MRI can provide
      information on coronary anatomy as well as cardiac function. * (Low-dose) CT
      angiography and CT calcium score can also provide important information. *
      Current guidelines for follow-up of patients with KD need to be revised. 

PMID- 26210917
TI  - Photoelectrochemical cell studies of Fe(2+) doped ZnSe nanorods using the
      potentiostatic mode of electrodeposition.
AB  - The Fe(2+) doped ZnSe nanorods are synthesized using simple potentiostatic mode
      of electrodeposition on the ITO substrate. In order to study the doping effect of
      Fe(2+) in ZnSe, varied the doing percent such as 0.5%, 1%, 1.5%. These films are
      characterized for structural, compositional, morphological, optical and
      electrochemical properties using the X-ray diffraction study (XRD), X-ray
      photoelectron spectroscopy, field emission scanning electron microscopy, UV-vis
      spectroscopy and electrochemical spectroscopy. Along with these Raman
      spectroscopy and photoluminescence spectroscopy have been studied for
      understanding the characteristics vibrations of ZnSe and luminescence of ZnSe
      nanorods. FE-SEM shows the nanorods like morphology. Photoelectrochemical cell
      performance studied using the J-V measurement and it shows the maximum efficiency
      at 1% Fe(2+) doped ZnSe nanorods. The observed maximum efficiency of Fe(2+) doped
      ZnSe nanorods is 0.32%. 

PMID- 26210918
TI  - pH-responsive fatty acid self-assembly transition induced by UV light.
AB  - Fatty acids are natural, pH-responsive surfactants. Their properties can be tuned
      by adding CO2 or by applying light which modify solution pH. We investigated
      photoresponsive systems based on fatty acids with different chain lengths in the
      presence of a photoacid generator (PAG). Under UV irradiation, photolysis of the
      PAG in aqueous solution resulted in a decrease in pH, triggering a change in
      fatty acid assembly. Using a multi-scale approach before and after UV
      irradiation, we characterized the effect of this pH decrease on the nature of the
      fatty acid self-assemblies. At the molecular scale, pH and infrared spectroscopy
      measurements were used to determine the fatty acid ionization state. At the
      microscopic scale, the self-assembled structure was characterized using small
      angle neutron scattering and microscopy. We showed that UV irradiation tuned the
      ionization state of the fatty acid molecules which in turn triggered a transition
      from spherical micelles to vesicles or lamellar phases, depending on fatty acid
      chain length. We studied the foaming properties of these systems before and after
      UV irradiation. We showed that after UV irradiation, foam stability was
      drastically enhanced as a result of a change in self-assembly. Our approach can
      be easily extended to various pH-responsive surfactants. 

PMID- 26210920
TI  - Pulmonary Artery Bleeding During Video-Assisted Thoracoscopic Surgery:
      Intraoperative Bleeding and Control.
AB  - With appropriate planning and operative technique, the risk of pulmonary artery
      injury and bleeding during video-assisted thoracoscopic surgery (VATS) lobectomy
      can be minimized. However, the risk cannot be completely eliminated; surgeons
      should always ensure that they are prepared to manage this situation if it
      occurs. Although pulmonary artery bleeding can potentially lead to intraoperative
      disasters, appropriate judgment, management, and control via VATS or conversion
      to thoracotomy can avoid any impact on either short-term or long-term patient
      outcomes. 

PMID- 26210919
TI  - Phosphorylation of serine 523 on 5-lipoxygenase in human B lymphocytes.
AB  - The key enzyme in leukotriene (LT) biosynthesis is 5-lipoxygenase (5-LO), which
      is expressed in myeloid cells and in B lymphocytes. There are three
      phosphorylation sites on 5-LO (Ser271, Ser523 and Ser663). Protein kinase A (PKA)
      phosphorylates 5-LO on Ser523. In this report, we demonstrate by immunoblotting
      that native 5-LO in mantle B cell lymphoma (MCL) cells (Granta519, JEKO1, and
      Rec1) and in primary chronic B lymphocytic leukemia cells (B-CLL) is
      phosphorylated on Ser523. In contrast, we could not detect phosphorylation of 5
      LO on Ser523 in human granulocytes or monocytes. Phosphorylated 5-LO was purified
      from Rec1 cells, using an ATP-agarose column, and the partially purified enzyme
      could be dephosphorylated with alkaline phosphatase. Incubation of Rec1 cells
      with 8-Br-cAMP or prostaglandin E2 stimulated phosphorylation at Ser523.
      Furthermore, FLAG-5LO was expressed in Rec1 cells, and the cells were cultivated
      in the presence of 8-Br-cAMP. The 5-LO protein from these cells was
      immunoprecipitated, first with anti-FLAG, followed by anti-pSer523-5-LO. The
      presence of 5-LO protein in the final precipitate further supported the finding
      that the protein recognized by the pSer523 antibody was 5-LO. Taken together,
      this study shows that 5-LO in B cells is phosphorylated on Ser523 and
      demonstrates for the first time a chemical difference between 5-LO in myeloid
      cells and B cells. 

PMID- 26210921
TI  - Intraoperative Tracheal Injury.
AB  - Intraoperative tracheal injury is a rare but potentially devastating
      complication. Transhiatal esophagectomy should be avoided in patients with
      proximal esophageal tumors who underwent neoadjuvant therapy, and percutaneous
      tracheostomy should be avoided in patients with short, thick necks. Early
      recognition leads to improved outcomes. Patients present with a sudden loss in
      airway pressure, air leaking into the operative field, or mediastinal and
      subcutaneous emphysema. Treatment starts with airway control. Primary buttressed
      repair is recommended, through either a left cervical incision for proximal
      injuries or a right thoracotomy for distal injuries. Nonoperative management has
      been used safely in select patients injured during intubation or tracheostomy. 

PMID- 26210922
TI  - Massive Airway Hemorrhage.
AB  - Massive hemoptysis is not an uncommon surgical problem. A systematic yet flexible
      and multidisciplinary approach leads to optimal outcomes. The initial focus
      should be on stabilizing patients and securing the airway, which should be
      followed by methods to stop the bleeding, preferably nonsurgical methods.
      Consideration for definitive therapy should ensue, including surgical therapy for
      appropriate patients. This review outlines the management of patients with
      massive hemoptysis from benign and malignant causes. 

PMID- 26210923
TI  - Great Vessel Injury in Thoracic Surgery.
AB  - The potential for intraoperative bleeding is inherent to the practice of thoracic
      surgery due to the presence of multiple vital vascular structures, complex
      anatomy, and constant cardiorespiratory motion. Careful and detailed preoperative
      evaluation and planning, comprehensive review of imaging studies, and a thorough
      knowledge of the operative procedure, anatomic relationships, and potential
      complications are of the highest importance in prevention and avoidance of
      bleeding complications. Preparation with a clear crisis management plan ensures
      an effective and expedited response when intraoperative bleeding occurs. 

PMID- 26210924
TI  - Endotracheal Tube Management and Obstructed Airway.
AB  - Thoracic surgery encompasses a wide array of surgical techniques, most of which
      require lung isolation for surgical exposure in the pleural cavity; this, in
      turn, demands an extensive knowledge of respiratory mechanics and modalities of
      airway control. Likewise, effective treatment of an acute central airway
      obstruction calls for a systematic approach using clear communication between
      teams and a comprehensive knowledge of available therapeutic modalities by the
      surgeon. 

PMID- 26210925
TI  - Operative and Perioperative Pulmonary Emboli.
AB  - Intraoperative and perioperative massive pulmonary emboli remain an unusual but
      well-established cause of death. Improved outcomes rely on a high index of
      suspicion, prompt recognition, and aggressive intervention. Surgical embolectomy
      outcomes have improved drastically since its inception as a technique at the turn
      of the previous century and should be used without hesitation during an
      intraoperative crisis in which pulmonary embolism has been determined to be the
      cause. There is an emerging trend toward a more aggressive approach. 

PMID- 26210926
TI  - Acute Intraoperative Pulmonary Aspiration.
AB  - Acute intraoperative aspiration is a potentially fatal complication with
      significant associated morbidity. Patients undergoing thoracic surgery are at
      increased risk for anesthesia-related aspiration, largely due to the predisposing
      conditions associated with this complication. Awareness of the risk factors,
      predisposing conditions, maneuvers to decrease risk, and immediate management
      options by the thoracic surgeon and the anesthesia team is imperative to reducing
      risk and optimizing patient outcomes associated with acute intraoperative
      pulmonary aspiration. Based on the root-cause analyses that many of the
      aspiration events can be traced back to provider factors, having an experienced
      anesthesiologist present for high-risk cases is also critical. 

PMID- 26210927
TI  - Coagulopathy and Anticoagulation During Thoracic Surgery.
AB  - Coagulopathy and bleeding in thoracic surgery may be compounded by the chronic
      use of anticoagulants and antiplatelet agents. Timely preoperative cessation and
      postoperative resumption of these antithrombotic drugs are critical in reducing
      the risks of perioperative major bleeding and thromboembolism. This article
      describes the various strategies for the optimal perioperative management of
      antithrombotics based on individual assessment of each patient and the most
      recent multisociety guidelines. 

PMID- 26210928
TI  - Cardiopulmonary Bypass and Extracorporeal Life Support for Emergent
      Intraoperative Thoracic Situations.
AB  - Intraoperative thoracic surgical catastrophes may require extracorporeal
      circulation modes to support the patient while the appropriate repair is made.
      Teamwork is key and, given the evidence supporting better performance with the
      use of simulation and surgical-crisis checklists, their use should be encouraged.
      Anticipation is another important factor because the results of intrathoracic
      malignancy resection are clearly superior in the setting of planned
      cardiopulmonary support. In addition, familiarity with the different modes of
      support that are currently available can direct the decision-making process
      toward the best option to facilitate resolution of the intraoperative catastrophe
      with the least related morbidity. 

PMID- 26210929
TI  - Management of Complications After Pneumonectomy.
AB  - Although mortalities have steadily declined over the last 80 years, morbidity
      after pneumonectomy remains significant. Appropriate patient selection and a
      proactive approach to perioperative management are essential to optimizing
      outcomes after pneumonectomy.

PMID- 26210930
TI  - Video-Assisted Thoracic Surgery After Median Sternotomy for Cardiac Surgery.
AB  - Video-assisted thoracic surgery (VATS) lobectomy has become a standard approach
      for early stage 1 lung cancer. However, concerns still remain regarding certain
      clinical situations, such as potential damage to the heart or bypass grafts when
      VATS is performed after median sternotomy for cardiac surgery. In this article,
      techniques are described to minimize risk to an internal mammary artery graft
      during a VATS anatomic pulmonary resection in this group of patients. The article
      reviews data on VATS after median sternotomy for cardiac surgery and describes
      techniques to prevent, treat, and mitigate problems in this group of patients.
      Management of intraoperative crises is also discussed. 

PMID- 26210932
TI  - Managing Intraoperative Events in Thoracic Surgery.

PMID- 26210931
TI  - Postlobectomy Early Complications.
AB  - Immediate postoperative complications are common after lobectomy. The most
      effective management of postoperative crises is prevention, which starts with
      preoperative preparation and patient screening. There are many factors that can
      be controlled and improved by the patient. Equally important is patient
      selection, which is influenced by pulmonary function tests, cardiopulmonary
      reserve, and preexisting comorbidities. After the operation, the care team can
      also greatly improve outcomes with aggressive cardiopulmonary therapies,
      ambulation, vigilant monitoring, and frequent assessments of the patient.
      Prevention strategies can minimize risks; however, when they occur, a proactive
      approach may minimize the long-term sequelae. 

PMID- 26210933
TI  - Investigation of the reactivation kinetics of a large series of bispyridinium
      oximes with organophosphate-inhibited human acetylcholinesterase.
AB  - The limited effectiveness of the established oximes obidoxime and pralidoxime
      resulted in ongoing research on novel oximes for the reactivation of
      acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OP). In
      order to get more insight into the ability of bispyridinium oximes to reactivate
      human AChE inhibited by structurally different OP the reactivation kinetics of 31
      compounds was determined with tabun-, cyclosarin- and paraoxon-inhibited AChE
      under identical experimental conditions. The determined affinity (KD), reactivity
      (kr) and hybrid reactivation rate constants (kr2) enabled theoretical
      calculations and gave insight into distinct structural features which are
      important for the reactivation of AChE inhibited by different OP. Several oximes
      with superior reactivating potency towards selective OP-AChE conjugates were
      identified but none of the tested oximes can be considered as a broad spectrum
      reactivator. In the end, the data of this and previous studies gives rise to the
      question whether further modifications of the bispyridinium structure could ever
      result in a universal reactivator or whether future research should be directed
      to different templates. 

PMID- 26210934
TI  - Conditioned medium from the stem cells of human dental pulp improves cognitive
      function in a mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative disease
      characterized by a decline in cognitive abilities and the appearance of beta
      amyloid plaques in the brain. Although the pathogenic mechanisms associated with
      AD are not fully understood, activated microglia releasing various neurotoxic
      factors, including pro-inflammatory cytokines and oxidative stress mediators,
      appear to play major roles. Here, we investigated the therapeutic benefits of a
      serum-free conditioned medium (CM) derived from the stem cells of human
      exfoliated deciduous teeth (SHEDs) in a mouse model of AD. The intranasal
      administration of SHEDs in these mice resulted in substantially improved
      cognitive function. SHED-CM contained factors involved in multiple
      neuroregenerative mechanisms, such as neuroprotection, axonal elongation,
      neurotransmission, the suppression of inflammation, and microglial regulation.
      Notably, SHED-CM attenuated the pro-inflammatory responses induced by beta
      amyloid plaques, and generated an anti-inflammatory/tissue-regenerating
      environment, which was accompanied by the induction of anti-inflammatory M2-like
      microglia. Our data suggest that SHED-CM may provide significant therapeutic
      benefits for AD. 

PMID- 26210935
TI  - Involvement of the caudal granular insular cortex in alcohol self-administration
      in rats.
AB  - Animal models of substance abuse have established a role for the caudal granular
      insular cortex (CGIC) in drug taking behaviour for several addictive substances,
      yet nothing has thus far been reported for alcohol. The current research was
      undertaken to examine the involvement of the CGIC in a rat model of alcohol self
      administration. We investigated the inactivating effects of local infusions of a
      gamma-aminobutyric acid agonist mixture (baclofen/muscimol) into the CGIC on
      alcohol self-administration under a fixed ratio-3 (FR-3). This inactivation of
      the CGIC decreased operant responding for alcohol along with a corresponding
      decrease in oral alcohol intake. Our results demonstrate the involvement of the
      CGIC in alcohol taking behaviour and suggest future studies examine the
      differential involvement of the various subregions of the insular cortex in
      various aspects of alcohol consumption. 

PMID- 26210938
TI  - Biogeography and divergent patterns of body size disparification in North
      American minnows.
AB  - Body size is one of the most important traits influencing an organism's ecology
      and a major axis of evolutionary change. We examined body size disparification in
      the highly speciose North American minnows (Cyprinidae), which exhibit diverse
      body sizes and ecologies, including the giant piscivorous pikeminnows. We
      estimated a novel phylogeny for 285 species based on a supermatrix alignment of
      seven mitochondrial and ten nuclear genes, and used this to reconstruct ancestral
      body sizes (log-total length) and ancestral area. Additionally, given that fishes
      inhabiting Pacific drainages have historically been subjected to frequent local
      extinctions due to periodic flooding, droughts, and low drainage connectivity, we
      also compared body size disparification between the highly speciose Atlantic
      drainages and comparatively depauperate Pacific drainages. We found that
      dispersal between Atlantic and Pacific drainages has been infrequent and
      generally occurred in minnows with southerly distributions, where drainage
      systems are younger and less stable. The long isolation between Atlantic and
      Pacific drainages has allowed for divergent patterns of morphological
      disparification; we found higher rates of body size disparification in minnows
      from the environmentally harsher Pacific drainages. We propose several possible
      explanations for the observed patterns of size disparification in the context of
      habitat stability, niche space, and species diversification. 

PMID- 26210937
TI  - Use of a force-sensing automated open field apparatus in a longitudinal study of
      multiple behavioral deficits in CAG140 Huntington's disease model mice.
AB  - Behavioral testing of mouse models of Huntington's disease (HD) is a key
      component of preclinical assessment for potential pharmacological intervention.
      An open field with a force plate floor was used to quantify numerous spontaneous
      behaviors in a slowly progressing model of HD. CAG140 (+/+, +/-, -/-) male and
      female mice were compared in a longitudinal study from 6 to 65 weeks of age.
      Distance traveled, wall rears, wall rear duration, number of low mobility bouts,
      in-place movements, number of high velocity runs, and gait parameters (stride
      rate, stride length, and velocity) were extracted from the ground reaction forces
      recorded in 20-min actometer sessions. Beginning at 11 weeks, HD mice (both +/-
      and +/+) were consistently hypoactive throughout testing. Robust hypoactivity at
      39 weeks of age was not accompanied by gait disturbances. By 52 and 65 weeks of
      age the duration of wall rears increased and in-place tremor-like movements
      emerged at 65 weeks of age in the +/+, but not in the +/- HD mice. Taken
      together, these results suggest that hypoactivity preceding frank motor
      dysfunction is a characteristic of CAG140 mice that may correspond to low
      motivation to move seen clinically in the premanifest/prediagnostic stage in
      human HD. The results also show that the force plate method provides a means for
      tracking the progression of behavioral dysfunction in HD mice beyond the stage
      when locomotion is lost while enabling quantification of tremor-like and similar
      in-place behaviors without a change in instrumentation. Use of force plate
      actometry also minimizes testing-induced enrichment effects when batteries of
      different tests are carried out longitudinally. 

PMID- 26210936
TI  - Rapastinel (GLYX-13) has therapeutic potential for the treatment of post
      traumatic stress disorder: Characterization of a NMDA receptor-mediated
      metaplasticity process in the medial prefrontal cortex of rats.
AB  - Rapastinel (GLYX-13) is a NMDA receptor modulator with glycine-site partial
      agonist properties. It is a robust cognitive enhancer and shows rapid and long
      lasting antidepressant properties in both animal models and in humans. Contextual
      fear extinction (CFE) in rodents has been well characterized and used extensively
      as a model to study the neurobiological mechanisms of post-traumatic stress
      disorder (PTSD). Since CFE is NMDA receptor modulated and neural circuitry in the
      medial prefrontal cortex (MPFC) regulates both depression and PTSD, studies were
      undertaken to examine the effects of rapastinel for its therapeutic potential in
      PTSD and to use rapastinel as a tool to study its underlying glutamatergic
      mechanisms. A 21-day chronic mild unpredictable stress (CUS) rat model was used
      to model depression and PTSD. The effects of CUS alone compared to No CUS
      controls, and the effects of rapastinel (3 mg/kg IV) on CUS-treated animals were
      examined. The effect of rapastinel was first assessed using CUS-treated rats in
      three depression models, Porsolt, sucrose preference, and novelty-induced
      hypophagia tests, and found to produce a complete reversal of the depressive-like
      state in each model. Rapastinel was then assessed in a MPFC-dependent positive
      emotional learning paradigm and in CFE and again a reversal of the impairments
      induced by CUS treatment was observed. Both synaptic plasticity and
      metaplasticity, as measured by the induction of long-term potentiation in rat
      MPFC slice preparations, was found to be markedly impaired in CUS-treated
      animals. This impairment was reversed when CUS-treated rats were administered
      rapastinel and tested 24 h later. Transcriptomic analysis of MPFC mRNA expression
      in CUS-treated rats corroborated the link between rapastinel's behavioral effects
      and synaptic plasticity. A marked enrichment in both the LTP and LTD connectomes
      in rapastinel-treated CUS rats was observed compared to CUS-treated controls. The
      effects of rapastinel on depression models, PEL, and most importantly on CFE
      demonstrate the therapeutic potential of rapastinel for the treatment of PTSD.
      Moreover, rapastinel appears to elicit its therapeutic effects through a NMDA
      receptor-mediated, LTP-like, metaplasticity process in the MPFC.

PMID- 26210939
TI  - Endovascular conversion into aorto-uniiliac configuration of acute failed
      endovascular aneurysm repair is associated with better one-year survival rates
      compared to open conversion.
AB  - BACKGROUND: Open conversions (OC) due to failed endovascular repair of infrarenal
      abdominal aortic aneurysms (EVAR) are technically demanding because of
      preexisting prostheses and advanced aortic disease. This study evaluates the
      feasibility and outcomes of aorto-uniiliac endografting (AUI) as an alternative
      treatment option in acute failed EVAR. METHODS: From March 1995 through February
      2012, 26 patients underwent acute conversion of failed EVAR at our tertiary care
      university center. All data were prospectively entered in our institutional
      database. Outcomes included 30-day or in-hospital mortality, postoperative
      complications, and mid-term survival. RESULTS: During the investigation period, a
      total of 692 patients received EVAR at our institution, while five of the 26
      patients with acute conversion (19.2%) had an initial EVAR at an outlying
      institution and were referred for treatment. Therefore, our estimated
      institutional rate of acute conversions was 3% (21 of 692 EVAR). OC were
      performed in 14 patients (53.8%), while 12 patients underwent AUI (46.2%). An
      average time of 20.3 months (median: 18.6; interquartile range Q1-Q3: 0.0-38.6)
      elapsed between the initial EVAR and the acute conversion. All acute AUI
      conversion procedures were completed successfully. The 30-day mortality following
      acute conversions was 42.3% and since the use of AUI, it could be reduced to
      33.3%. Kaplan-Meier estimates revealed a survival advantage for AUI at one year
      (p = 0.046), but the benefit was lost by mid-term follow-up (p = 0.103).
      CONCLUSIONS: AUI for the treatment of acute failed EVAR represents a feasible and
      less invasive alternative to OC, and is associated with better one-year survival
      rates.

PMID- 26210940
TI  - [11C]acetate and PET/CT assessment of muscle activation in rat studies.
AB  - PURPOSE: The purpose of the present study is to apply kinetic analysis to
      investigate exercise-related changes in the metabolism of the skeletal muscle of
      the rat hindlimb by [[Formula: see text]]acetate positron emission tomography and
      computed tomography (PET/CT). METHODS: Contractions were induced in Wistar rats'
      left hindlimb by electrostimulation of the Vastus Lateralis muscle motor point.
      After 15 min of muscle contractions, [[Formula: see text]]acetate was injected
      and PET/CT of both hindlimbs was acquired. The resting hindlimb was used as a
      control reference. The kinetic parameters [Formula: see text] and [Formula: see
      text] were calculated for the target muscles (exercised and control) and
      correlated with the corresponding standardized uptake values (SUVs). The ratio
      between each kinetic parameter values and the SUV extracted for the exercised
      muscle and the muscle at rest was computed ([Formula: see text] and [Formula: see
      text], respectively). RESULTS: Kinetic analysis quantitatively confirmed that net
      tracer uptake ([Formula: see text]) and washout ([Formula: see text]) were
      significantly higher in exercised muscles ([Formula: see text] for exercised
      muscles vs. [Formula: see text] for resting muscles, [Formula: see text];
      [Formula: see text] for exercised muscle vs. [Formula: see text] for resting
      muscle, [Formula: see text]). On the other hand, SUV was not significantly
      different between active and inactive muscles ([Formula: see text] for exercised
      muscles vs. [Formula: see text] for resting muscles). Linear regression analysis
      revealed a good correlation ([Formula: see text]) between net tracer uptake ratio
      ([Formula: see text]) and the SUV ratio [Formula: see text]). A lower correlation
      was found between the net tracer washout ratio ([Formula: see text]) and the SUV
      ratio ([Formula: see text]). CONCLUSION: The present study showed that kinetic
      modelling can detect changes between active and inactive skeletal muscles with a
      higher sensitivity with respect to the SUV, when performed with [[Formula: see
      text]]acetate PET/CT.

PMID- 26210941
TI  - Statistical study of parameters for deep brain stimulation automatic preoperative
      planning of electrodes trajectories.
AB  - PURPOSE: Automatic methods for preoperative trajectory planning of electrodes in
      deep brain stimulation are usually based on the search for a path that resolves a
      set of surgical constraints to propose an optimal trajectory. The relative
      importance of each surgical constraint is usually defined as weighting parameters
      that are empirically set beforehand. The objective of this paper is to analyze
      the use of these parameters thanks to a retrospective study of trajectories
      manually planned by neurosurgeons. For that purpose, we firstly retrieved
      weighting factors allowing to match neurosurgeons manually planned choice of
      trajectory on each retrospective case; secondly, we compared the results from two
      different hospitals to evaluate their similarity; and thirdly, we compared the
      trends to the weighting factors empirically set in most current approaches.
      METHODS: To retrieve the weighting factors best matching the neurosurgeons manual
      plannings, we proposed two approaches: one based on a stochastic sampling of the
      parameters and the other on an exhaustive search. In each case, we obtained a
      sample of combinations of weighting parameters with a measure of their quality,
      i.e., the similarity between the automatic trajectory they lead to and the one
      manually planned by the surgeon as a reference. Visual and statistical analyses
      were performed on the number of occurrences and on the rank means. RESULTS: We
      performed our study on 56 retrospective cases from two different hospitals. We
      could observe a trend of the occurrence of each weight on the number of
      occurrences. We also proved that each weight had a significant influence on the
      ranking. Additionally, we observed no influence of the medical center parameters,
      suggesting that the trends were comparable in both hospitals. Finally, the
      obtained trends were confronted to the usual weights chosen by the community,
      showing some common points but also some discrepancies. CONCLUSION: The results
      tend to show a predominance of the choice of a trajectory close to a standard
      direction. Secondly, the avoidance of the vessels or sulci seems to be sought in
      the surroundings of the standard position. The avoidance of the ventricles seems
      to be less predominant, but this could be due to the already reasonable distance
      between the standard direction and the ventricles. The similarity of results
      between two medical centers tends to show that it is not an exceptional practice.
      These results suggest that manual planning software may introduce a bias in the
      planning by proposing a standard position.

PMID- 26210942
TI  - MICCAI 2014 special issue.

PMID- 26210943
TI  - Refinement and validation of the Work Readiness Scale for graduate nurses.
AB  - The transition from student to registered nurse is often stressful and has been
      attributed to a lack of work readiness. Understanding what comprises work
      readiness for newly registered nurses, or graduate nurses as they are referred to
      in Australia, may reduce attrition and improve transition into the workplace. The
      64-item Work Readiness Scale (WRS), developed with a generic population of
      graduates, has yet to be validated against specific disciplines to confirm
      applicability as a measure of work readiness. This study adapted the original WRS
      for use with a graduate nurse population (WRS-GN). The aim was to refine and
      validate the WRS-GN and determine whether the original four factor construct was
      supported. The WRS-GN was completed by 450 graduate nurses. Exploratory factor
      analyses supported the original four-factor solution (social intelligence,
      personal work characteristics, organizational acumen, and work competence). The
      final WRS-GN consisted of 46 items, showed excellent reliability, and explained
      73.55% of the variance.

PMID- 26210944
TI  - Heterogeneity and the effect of mental health parity mandates on the labor
      market.
AB  - Health insurance benefit mandates are believed to have adverse effects on the
      labor market, but efforts to document such effects for mental health parity
      mandates have had limited success. I show that one reason for this failure is
      that the association between parity mandates and labor market outcomes vary with
      mental distress. Accounting for this heterogeneity, I find adverse labor market
      effects for non-distressed individuals, but favorable effects for moderately
      distressed individuals and individuals with a moderately distressed family
      member. On net, I conclude that the mandates are welfare increasing for
      moderately distressed workers and their families, but may be welfare decreasing
      for non-distressed individuals. 

PMID- 26210945
TI  - Pediatricians' Experience with Clinical Ethics Consultation: A National Survey.
AB  - OBJECTIVE: To conduct a national survey of pediatricians' access to and
      experience with clinical ethics consultation. STUDY DESIGN: We surveyed a
      randomly selected sample of 3687 physician members of the American Academy of
      Pediatrics. We asked about their experiences with ethics consultation, the
      helpfulness of and barriers to consultation, and ethics education. Using a
      discrete choice experiment with maximum difference scaling, we evaluated which
      traits of ethics consultants were most valuable. RESULTS: Of the total sample of
      3687 physicians, 659 (18%) responded to the survey. One-third of the respondents
      had no experience with clinical ethics consultation, and 16% reported no access
      to consultation. General pediatricians were less likely to have access. The vast
      majority (90%) who had experience with consultation had found it helpful. Those
      with fewer years in practice were more likely to have training in ethics. The
      most frequently reported issues leading to consultation concerned end-of-life
      care and conflicts with patients/families or among the team. Intensive care unit
      physicians were more likely to have requested consultation. Mediation skills and
      ethics knowledge were the most highly valued consultant characteristics, and
      representing the official position of the hospital was the least-valued
      characteristic. CONCLUSION: There is variability in pediatricians' access to
      ethics consultation. Most respondents reported that consultation had been helpful
      in the past. Determining ethically appropriate end-of-life care and mediation of
      disagreements are common reasons that pediatricians request consultation.

PMID- 26210946
TI  - What Is the Optimal Transplant for Older Patients With Idiopathic Pulmonary
      Fibrosis?
AB  - BACKGROUND: There is controversy regarding the optimal type of lung transplant-
      single orthotopic lung transplantation (SOLT) versus bilateral orthotopic lung
      transplantation (BOLT)--for patients with idiopathic pulmonary fibrosis. We
      performed this study to determine which type of transplant is more appropriate
      for older patients with this condition. METHODS: We conducted a review of the
      United Network for Organ Sharing database from 2005 to 2013 for patients aged 65
      years or more with idiopathic pulmonary fibrosis. A 1:1 nearest-neighbor
      propensity match was utilized to determine differences in survival by transplant
      procedure type (SOLT versus BOLT). Logistic regression modeling taking into
      account interaction terms between prespecified variables and the type of
      transplant was utilized to determine variables that altered the survival outcomes
      associated with SOLT versus BOLT. RESULTS: Of 1,564 patients who met study
      criteria, 521 (33.3%) received BOLT. After propensity matching 498 BOLT
      recipients to 498 SOLT recipients, BOLT was associated with a significantly
      improved 5-year survival (48.7% versus 35.2%, p < 0.01). However, the mortality
      hazard associated with BOLT varied from a nonsignificant reduction in survival
      within 3 months after transplant (hazard ratio 1.24, 95% confidence interval:
      0.80 to 1.93) to a significant survival benefit for patients who survived beyond
      1 year (hazard ratio 0.64, 95% confidence interval: 0.47 to 0.86). Functional
      status was also found to be a significant predictor of the survival benefit
      associated with BOLT. CONCLUSIONS: Bilateral orthotopic lung transplantation is
      associated with significantly improved survival over SOLT for older patients with
      idiopathic pulmonary fibrosis, driven by a late survival benefit from bilateral
      transplantation. However, patients with a reduced preoperative functional status
      do not appear to derive a similar benefit from bilateral transplantation.

PMID- 26210947
TI  - Survival in Adult Lung Transplant Recipients Receiving Pediatric Versus Adult
      Donor Allografts.
AB  - BACKGROUND: Recent evidence showed that pediatric donor lungs increased rates of
      allograft failure in adult lung transplant recipients; however, the influence on
      survival is unclear. METHODS: The United Network for Organ Sharing (UNOS)
      database was queried from 2005 to 2013 for adult lung transplant recipients (>=18
      years) to assess survival differences among donor age categories (<18 years, 18
      to 29 years, 30 to 59 years, >=60 years). RESULTS: Of 12,297 adult lung
      transplants, 12,209 were used for univariate Cox models and Kaplan-Meier (KM)
      analysis and 11,602 for multivariate Cox models. A total of 1,187 adult
      recipients received pediatric donor lungs compared with 11,110 receiving adult
      donor organs. Univariate and multivariate Cox models found no difference in
      survival between donor ages 0 to 17 and donor ages 18 to 29, whereas donor ages
      60 and older were significantly associated with increased mortality hazard,
      relative to the modal category of donor ages 30 to 59 (adjusted hazard ratio =
      1.381; 95% confidence interval = 1.188% to 1.606%; p < 0.001). Interactions
      between recipient and donor age range found that the oldest donor age range was
      negatively associated with survival among middle-aged (30 to 59) and older (>=60)
      lung transplant recipients. CONCLUSIONS: Pediatric donor lung allografts were not
      negatively associated with survival in adult lung transplant recipients; however,
      the oldest donor age range was associated with increased mortality hazard for
      adult lung transplant recipients.

PMID- 26210948
TI  - Effect of Transient Inactivation of Ventral Tegmental Area on the Expression and
      Acquisition of Nicotine-Induced Conditioned Place Preference in Rats.
AB  - BACKGROUND: Nicotine can activate dopaminergic neurons within the ventral
      tegmental area (VTA). However, there is no evidence about complete inhibition of
      VTA on nicotine reinforcement. METHODS: in the present study, we used conditioned
      place preference (CPP) method to study the effect of transient inhibition of left
      and/or right side of the VTA by lidocaine on nicotine reward properties. Male
      Wistar rats seven days after recovery from surgery and cannulation were
      conditioned to nicotine (1.5 mg/kg) in an unbiased designed CPP apparatus. Five
      min before each nicotine injection in conditioning phase, lidocaine (2%) was
      administered either uni- or bi-laterally into the VTA (0.5ul/rat). RESULTS:
      results revealed that lidocaine administration into the left but not right side
      of the VTA reduced nicotine CPP significantly. The reduction was potentiated when
      lidocaine injected in to both sides of the VTA. In addition, the number of
      compartment crossing was reduced when lidocaine injected in both side of VTA as
      well as left side. On the other hand, rearing was reduced when lidocaine injected
      to the right but not left side of VTA. At last, sniffing was reduced only in the
      group in which received lidocaine in both side of VTA. Sniffing and rearing
      increased in the group in which received lidocaine in right side. CONCLUSION: It
      is concluded that the right and left side of VTA play different role in nicotine
      induced activity and reward.

PMID- 26210949
TI  - Acute and long-term exposure to chlorpyrifos induces cell death of basal
      forebrain cholinergic neurons through AChE variants alteration.
AB  - Chlorpyrifos (CPF) is one of the most widely used organophosphates insecticides
      that has been reported to induce cognitive disorders both after acute and
      repeated administration similar to those induced in Alzheimer's disease (AD).
      However, the mechanisms through which it induces these effects are unknown. On
      the other hand, the cholinergic system, mainly basal forebrain cholinergic
      neurons, is involved in learning and memory regulation, and an alteration of
      cholinergic transmission or/and cholinergic cell loss could induce these effects.
      In this regard, it has been reported that CPF can affect cholinergic
      transmission, and alter AChE variants, which have been shown to be related with
      basal forebrain cholinergic neuronal loss. According to these data, we
      hypothesized that CPF could induce basal forebrain cholinergic neuronal loss
      through cholinergic transmission and AChE variants alteration. To prove this
      hypothesis, we evaluated in septal SN56 basal forebrain cholinergic neurons, the
      CPF toxic effects after 24h and 14 days exposure on neuronal viability and the
      cholinergic mechanisms related to it. This study shows that CPF impaired
      cholinergic transmission, induced AChE inhibition and, only after long-term
      exposure, increased CHT expression, which suggests that acetylcholine levels
      alteration could be mediated by these actions. Moreover, CPF induces, after acute
      and long-term exposure, cell death in cholinergic neurons in the basal forebrain
      and this effect is independent of AChE inhibition and acetylcholine alteration,
      but was mediated partially by AChE variants alteration. Our present results
      provide a new understanding of the mechanisms contributing to the harmful effects
      of CPF on neuronal function and viability, and the possible relevance of CPF in
      the pathogenesis of neurodegenerative diseases. 

PMID- 26210950
TI  - Propagation of the Israeli vaccine strain of Anaplasma centrale in tick cell
      lines.
AB  - Anaplasma centrale has been used in cattle as a live blood vaccine against the
      more pathogenic Anaplasma marginale for over 100 years. While A. marginale can be
      propagated in vitro in tick cell lines, facilitating studies on antigen
      production, immunisation and vector-pathogen interaction, to date there has been
      no in vitro culture system for A. centrale. In the present study, 25 cell lines
      derived from 13 ixodid tick species were inoculated with the Israeli vaccine
      strain of A. centrale and monitored for at least 12 weeks by microscopic
      examination of Giemsa-stained cytocentrifuge smears. Infection of 19 tick cell
      lines was subsequently attempted by transfer of cell-free supernate from vaccine
      inoculated tick cells. In two separate experiments, rickettsial inclusions were
      detected in cultures of the Rhipicephalus appendiculatus cell line RAE25 28-32
      days following inoculation with the vaccine. Presence of A. centrale in the RAE25
      cells was confirmed by PCR assays targeting the 16S rRNA, groEL and msp4 genes;
      sequenced PCR products were 100% identical to published sequences of the
      respective genes in the Israeli vaccine strain of A. centrale. A. centrale was
      taken through three subcultures in RAE25 cells over a 30 week period. In a single
      experiment, the Dermacentor variabilis cell line DVE1 was also detectably
      infected with A. centrale 11 weeks after inoculation with the vaccine.
      Availability of an in vitro culture system for A. centrale in tick cells opens up
      the possibility of generating a safer and more ethical vaccine for bovine
      anaplasmosis. 

PMID- 26210952
TI  - Overview of Clinical Pathology and the Horse.
AB  - This article is intended to serve as a reference for clinical pathology in the
      equine with algorithms and tables provided for anemia diagnosis and leukogram
      alterations associated with both acute and chronic inflammation. A table of
      reference is provided for fluid evaluations including joint fluid and effusions
      into body cavities. Evaluation of newer serum markers, such as cardiac troponin,
      and a table highlighting test procedures for the evaluation of endocrine disease
      in the horse are included. A brief overview of quality assurance in the
      laboratory is provided to stimulate interest in this important aspect of
      laboratory diagnosis of disease. 

PMID- 26210951
TI  - Mucosally administered Lactobacillus surface-displayed influenza antigens (sM2
      and HA2) with cholera toxin subunit A1 (CTA1) Induce broadly protective immune
      responses against divergent influenza subtypes.
AB  - The development of a universal influenza vaccine that provides broad cross
      protection against existing and unforeseen influenza viruses is a critical
      challenge. In this study, we constructed and expressed conserved sM2 and HA2
      influenza antigens with cholera toxin subunit A1 (CTA1) on the surface of
      Lactobacillus casei (pgsA-CTA1sM2HA2/L. casei). Oral and nasal administrations of
      recombinant L. casei into mice resulted in high levels of serum immunoglobulin G
      (IgG) and their isotypes (IgG1 & IgG2a) as well as mucosal IgA. The mucosal
      administration of pgsA-CTA1sM2HA2/L. casei may also significantly increase the
      levels of sM2- or HA2-specific cell-mediated immunity because increased release
      of both IFN-gamma and IL-4 was observed. The recombinant pgsA-CTA1sM2HA2/L. casei
      provided better protection of BALB/c mice against 10 times the 50% mouse lethal
      doses (MLD50) of homologous A/EM/Korea/W149/06(H5N1) or A/Aquatic
      bird/Korea/W81/2005 (H5N2) and heterologous A/Puerto Rico/8/34(H1N1), or
      A/Chicken/Korea/116/2004(H9N2) or A/Philippines/2/08(H3N2) viruses, compared with
      L. casei harboring sM2HA2 and also the protection was maintained up to seven
      months after administration. These results indicate that recombinant L. casei
      expressing the highly conserved sM2, HA2 of influenza and CTA1 as a mucosal
      adjuvant could be a potential mucosal vaccine candidate or tool to protect
      against divergent influenza viruses for human and animal. 

PMID- 26210953
TI  - Neurologic Diseases in Horses.
AB  - This article focuses on the gross examination of the brain and spinal cord and
      outlines the main lesions and neuroanatomic location related to neurologic
      diseases in horses. 

PMID- 26210954
TI  - Reproductive Disorders in Horses.
AB  - Reproductive disease is relatively common in the horse, resulting in a variable,
      yet significant, economic impact on individual horsemen as well as the entire
      industry. Diverse expertise from the veterinary community ensures and improves
      individual and population health of the horse. From a pathology and diagnostics
      perspective, this review provides a comprehensive overview of pathology of the
      male and female equine reproductive tract. Recognition by clinical and gross
      features is emphasized, although some essential histologic parameters are
      included, as appropriate. Where relevant, discussion of ancillary diagnostic
      tests and approaches are included for some diseases and lesions. 

PMID- 26210955
TI  - Ocular Pathology.
AB  - Although not comprehensive of all ocular conditions in the equine species, this
      article concentrates on various ophthalmic conditions observed in the horse where
      laboratory diagnostics are recommended. The importance of laboratory diagnostic
      testing cannot be underestimated with equine ophthalmic disease. In many cases,
      laboratory diagnostics can aid in obtaining an early diagnosis and determining
      appropriate therapy, which in turn, can provide a better prognosis. In
      unfortunate cases where ocular disease results in a blind, painful eye
      necessitating enucleation, light microscopic evaluation is imperative to
      determine or confirm the cause of the blindness and provide a prognosis for the
      contralateral eye. 

PMID- 26210956
TI  - Small-molecule kinase inhibitors: an analysis of FDA-approved drugs.
AB  - Small-molecule kinase inhibitors (SMKIs), 28 of which are approved by the US Food
      and Drug Administration (FDA), have been actively pursued as promising targeted
      therapeutics. Here, we assess the key structural and physicochemical properties,
      target selectivity and mechanism of function, and therapeutic indications of
      these approved inhibitors. Our analysis showed that >30% of approved SMKIs have a
      molecule weight (MW) exceeding 500 and all have a total ring count of between
      three and five. The assumption that type II inhibitors tend to be more selective
      than type I inhibitors has been proved to be unreliable. Although previous SMKI
      research was concentrated on tyrosine kinase inhibitors for cancer treatment,
      recent progress indicates diversification of SMKI research in terms of new
      targets, mechanistic types, and therapeutic indications. 

PMID- 26210957
TI  - Evading innate immunity in nonviral mRNA delivery: don't shoot the messenger.
AB  - In the field of nonviral gene therapy, in vitro transcribed (IVT) mRNA has
      emerged as a promising tool for the delivery of genetic information. Over the
      past few years it has become widely known that the introduction of IVT mRNA into
      mammalian cells elicits an innate immune response that has favored mRNA use
      toward immunotherapeutic vaccination strategies. However, for non-immunotherapy
      related applications this intrinsic immune-stimulatory activity directly
      interferes with the aimed therapeutic outcome, because it can seriously
      compromise the expression of the desired protein. This review presents an
      overview of the immune-related obstacles that limit mRNA advance for non
      immunotherapy-related applications. 

PMID- 26210958
TI  - Antiadenovirus drug discovery: potential targets and evaluation methodologies.
AB  - Human adenoviruses (HAdV) are the cause of many acute infections, mostly in the
      respiratory and gastrointestinal (GI) tracts, as well as conjunctivitis. HAdV
      diseases in immunocompetent individuals are mostly self-limiting; however, in
      immunocompromised individuals, especially in pediatric units, HAdV infections are
      the cause of high morbidity and mortality. Despite the significant clinical
      impact, there are currently no approved antiviral therapies for HAdV infections.
      Here, we provide an overview of the different targets that could be considered
      for the design of specific drugs against HAdV, as well as the available in vitro
      and in vivo tools for the screening and evaluation of candidate molecules. 

PMID- 26210959
TI  - Molecular neurobiological clues to the pathogenesis of bipolar disorder.
AB  - Bipolar disorder is a serious psychiatric disorder, with a high heritability and
      unknown pathogenesis. Recent genome-wide association studies have identified the
      first loci, implicating genes such as CACNA1C and ANK3. The genes highlight
      several pathways, notably calcium signalling, as being of importance. Molecular
      studies suggest that the risk variants impact on gene regulation and expression.
      Preliminary studies using reprogrammed patient-derived cells report alterations
      in the transcriptome and in cellular adhesion and differentiation. Mouse models
      show that genes involved in circadian biology, acting via dopaminergic effects,
      reproduce aspects of the bipolar phenotype. These findings together represent
      significant advances in identification of the genetic and molecular basis of
      bipolar disorder, yet we are still far from an integrated, evidence-based
      understanding of its aetiopathogenesis. 

PMID- 26210960
TI  - Dynamic and static tibial translation in patients with anterior cruciate ligament
      deficiency initially treated with a structured rehabilitation protocol.
AB  - PURPOSE: To compare dynamic and static tibial translation, in patients with
      anterior cruciate ligament deficiency, at 2- to 5-year follow-up, with the tibial
      translation after 4 months of rehabilitation initiated early after the injury.
      Secondarily, to compare tibial translation in the injured knee and non-injured
      knee and explore correlations between dynamic and static tibial translation.
      METHODS: Twelve patients with ACL rupture were assessed at 3-8 weeks after ACL
      injury, after 4 months of structured rehabilitation, and 2-5 years after ACL
      injury. Sagittal tibial translation was measured during the Lachman test (static
      translation) and during gait (dynamic translation) using a CA-4000
      electrogoniometer. RESULTS: Static tibial translation was increased bilateral 2-5
      years after ACL injury, whereas the dynamic tibial translation was unchanged.
      Tibial translation was greater in the injured knee compared with the non-injured
      knee (Lachman test 134 N 9.1 +/- 1.0 vs. 7.0 +/- 1.7 mm, P = 0.001, gait 5.6 +/-
      2.1 vs. 4.7 +/- 1.8 mm, P = 0.011). There were no correlations between dynamic
      and static tibial translation. CONCLUSION: Dynamic tibial translation was
      unchanged in spite of increased static tibial translation in the ACL-deficient
      knee at 2- to 5-year follow-up compared to directly after rehabilitation. Dynamic
      tibial translation did not correlate with the static tibial translation. A more
      normal gait kinematics may be maintained from completion of a rehabilitation
      programme to mid-term follow-up in patients with ACL deficiency treated with
      rehabilitation only. LEVEL OF EVIDENCE: IV.

PMID- 26210961
TI  - The contribution of the tibial tubercle to patellar instability: analysis of
      tibial tubercle-trochlear groove (TT-TG) and tibial tubercle-posterior cruciate
      ligament (TT-PCL) distances.
AB  - PURPOSE: The purpose of this study is to assess the reliability of measuring the
      tibial tubercle to posterior cruciate (TT-PCL) distance compared to the tibial
      tubercle to trochlear groove (TT-TG) distance on magnetic resonance imaging
      (MRI), establish baseline TT-PCL values in patellar instability patients, and
      determine the predictive value of an excessive TT-PCL distance (>=24 mm) for
      recurrent patellar instability compared to a TT-TG distance >=20 mm. METHODS: TT
      TG and TT-PCL distances were calculated on MRI in a randomized and blinded
      fashion by two reviewers on 54 patients (59 knees) with patellar instability.
      Interobserver reliability was assessed using interclass correlation coefficients
      (ICC). TT-PCL distances were also assessed to establish mean values in patellar
      instability patients. The ability of excessive TT-PCL and TT-TG distances to
      predict recurrent instability was assessed by comparing odds ratios,
      sensitivities, and specificities. RESULTS: Interobserver reliability was
      excellent for both TT-TG (ICC = 0.978) and TT-PCL (ICC = 0.932). The mean TT-PCL
      in these 59 knees was 21.7 mm (standard deviation 4.1 mm). Twelve (20 %) of 59
      knees had a single dislocation, and 47 (80 %) exhibited 2 or more dislocations.
      The odds ratios, sensitivities, and specificities of a TT-TG distance >=20 mm for
      identifying patients with recurrent dislocation were 5.38, 0.213, and 1.0,
      respectively, while those of a TT-PCL distance >=24 mm were 1.46, 0.298, and
      0.583, respectively. Of the 10 knees with a TT-TG distance >=20 mm, all 10 (100
      %) had recurrent instability, while 14 (73.7 %) of the 19 knees with a TT-PCL
      >=24 mm experienced multiple dislocations (n.s.). CONCLUSION: Both TT-PCL and TT
      TG can be measured on MRI with excellent interobserver reliability. In this
      series, the mean TT-PCL value in patients with patellar instability was 21.8 mm,
      but the range was broad. A TT-PCL distance >=24 mm was found to be less
      predictive of recurrent instability in this series. For patients experiencing
      multiple episodes of patellar instability in the setting of a normal TT-TG
      distance, obtaining the TT-PCL measurement may provide a more focused assessment
      of the tibial contribution to tubercle lateralization. LEVEL OF EVIDENCE: III.

PMID- 26210962
TI  - No advantage of adrenaline in the local infiltration analgesia mixture during
      total knee arthroplasty.
AB  - PURPOSE: Local infiltration analgesia (LIA) is widely applied in patients
      undergoing total knee arthroplasty (TKA). In daily practice, adrenaline is added
      to the LIA mixture to achieve vasoconstriction. However, adrenaline has some
      possible negative side effects (e.g. tissue necrosis). This trial investigated
      whether ropivacaine alone is at least as effective for postoperative pain relief
      after LIA. METHODS: Fifty patients scheduled for primary TKA were included in
      this prospective randomized, double-blind, controlled pilot study receiving high
      volume (150 mL) single-shot intra-capsular LIA with ropivacaine (2 %) with
      (Ropi+) or without (Ropi-) adrenaline (0.01 %). All patients received the same
      pre-, peri- and postoperative care with multimodal oral pain protocol.
      Postoperative pain was assessed before and after the first mobilization and
      during the first 48 h postoperative using the visual analogue scale (VAS).
      Secondary outcomes were rescue medication use, early mobilization, length of
      hospital stay, adverse events (AE's) and readmission rates. Patient reported
      outcomes measures (PROMS); Oxford Knee Score and WOMAC, were obtained
      preoperative and 3 months postoperative. RESULTS: VAS scores were not
      significantly different before (n.s.) and after the first mobilization (n.s.),
      neither over the first 48 h postoperative (n.s.). Patients who needed rescue
      medication (n.s.), who mobilized <6 h postoperative (n.s.), who were discharged
      before postoperative day 3 (n.s.), AE's and readmission rate (n.s.) were
      comparable between both groups. At 3-month follow-up, PROMS significantly
      improved within both groups. CONCLUSION: To prevent possible negative side
      effects (e.g. tissue necrosis), adrenaline should be omitted from the LIA
      mixture. Single-shot LIA with ropivacaine alone results in clinical acceptable
      adequate pain control and can be used in daily TKA practice. LEVEL OF EVIDENCE:
      Randomized, double-blind, prospective clinical trial, Level I.

PMID- 26210963
TI  - Discrepancy between morphological findings in juvenile osteochondritis dissecans
      (OCD): a comparison of magnetic resonance imaging (MRI) and arthroscopy.
AB  - PURPOSE: The aim of this study was to assess the reliability of preoperative MRI
      for the staging of osteochondritis dissecans (OCD) lesions of the knee and the
      talus in juvenile patients, using arthroscopy as the gold standard of diagnosis.
      METHODS: Sixty-three juvenile patients (range 8-16 years) with an OCD of the knee
      or the talus underwent arthroscopy after MRI. In 54/9 out of 63 cases, 1.5/3 T MR
      scanners were used. The OCD stage was classified according the staging criteria
      of Dipaola et al. Arthroscopic findings were compared with MRI reports in each
      patient. RESULTS: From the 63 juvenile patients, MRI/arthroscopy revealed a stage
      I OCD in 4/19 patients, stage II in 31/22 patients, stage III in 22/9 patients
      and stage IV in 6/6 patients. No osteochondral pathology was evident in
      arthroscopy in seven out of 63 patients. The overall accuracy of preoperative MRI
      in staging an OCD lesion of the knee or the talus was 41.3%. In 33 out of 63
      patients (52.4%), arthroscopy revealed a lower OCD stage than in the preoperative
      MRI grading, and in four out of 63 cases (6.4%), the intraoperative arthroscopic
      grading was worse than in preoperative MRI prior to surgery. The utilization of
      the 3 T MRI provided a correct diagnosis with 44.4%. CONCLUSIONS: Even with
      today's modern MRI scanners, it is not possible to predict an accurate OCD stage
      in children. The children's orthopaedist should not solely rely on the MRI when
      it comes to the decision to further conservative or surgical treatment of a
      juvenile OCD, but rather should take surgical therapy in consideration within
      persisting symptoms despite a low OCD stage provided by MRI. LEVEL OF EVIDENCE:
      III.

PMID- 26210965
TI  - Concepts for Developing Expert Surgical Teams Using Simulation.
AB  - This article investigates how simulation-based training can enhance the
      effectiveness of surgical teams. First, a description of team training within
      surgical settings is provided. Then, empirical work from a variety of fields is
      introduced to describe common characteristics of expert teams, with a specific
      focus on training surgical teams in simulated settings. Finally, methods and
      suggestions for evaluation of simulation-based team training are discussed. 

PMID- 26210964
TI  - Applying Educational Theory to Simulation-Based Training and Assessment in
      Surgery.
AB  - Considerable progress has been made regarding the range of simulator technologies
      and simulation formats. Similarly, results from research in human learning and
      behavior have facilitated the development of best practices in simulation-based
      training (SBT) and surgical education. Today, SBT is a common curriculum
      component in surgical education that can significantly complement clinical
      learning, performance, and patient care experiences. Beginning with important
      considerations for selecting appropriate forms of simulation, several relevant
      educational theories of learning are described. 

PMID- 26210966
TI  - Simulation and Faculty Development.
AB  - As members of the faculty, surgeons take on a variety of roles related to the use
      of simulation. Surgeons will continue to interact with simulation as learners
      given the emerging role of simulation in continuing medical education. Surgeons
      who regularly teach others will also be using simulation because of its unique
      properties as an instructional method. Leading a simulation effort requires
      vision, creativity in resource management, and team leadership skills. Surgeons
      can use simulation to innovate in surgical patient care and in surgical
      education. 

PMID- 26210967
TI  - The Evolving Role of Simulation in Teaching Surgery in Undergraduate Medical
      Education.
AB  - Simulation-based training (SBT) over the last 10 years has become a mainstay for
      surgical education at the graduate medical education (GME) level. More recently,
      however, the technique has rapidly become the standard for early efficient
      teaching of surgical skills and decision making at the undergraduate medical
      education (UME) level. The described benefits of SBT include its ability to
      compartmentalize education, to combine immediate assessment and feedback, and to
      accelerate knowledge and skill acquisition for the young learner. Consequently,
      SBT is now being adopted in multiple national medical student surgical
      educational initiatives.

PMID- 26210968
TI  - Using Simulation in Interprofessional Education.
AB  - Simulation-based training (SBT) is a powerful educational tool permitting the
      acquisition of surgical knowledge, skills, and attitudes at both the individual-
      and team-based level in a safe, nonthreatening learning environment at no risk to
      a patient. Interprofessional education (IPE), in which participants from 2 or
      more health or social care professions learn interactively, can help improve
      patient care through the promotion of efficient coordination, dissemination of
      advances in care across specialties and professions, and optimization of
      individual- and team-based function. Nonetheless, conducting SBT IPE sessions
      poses several tactical and strategic challenges that must be effectively overcome
      to reap IPE's benefits. 

PMID- 26210969
TI  - Current Status of Simulation-Based Training in Graduate Medical Education.
AB  - The use of simulation in Graduate Medical Education has evolved significantly
      over time, particularly during the past decade. The applications of simulation
      include introductory and basic technical skills, more advanced technical skills,
      and nontechnical skills, and simulation is gaining acceptance in high-stakes
      assessments. Simulation-based training has also brought about paradigm shifts in
      the medical and surgical education arenas and has borne new and exciting national
      and local consortia that will ensure that the scope and impact of simulation will
      continue to broaden. 

PMID- 26210970
TI  - National Simulation-Based Training of Fellows: The Vascular Surgery Example.
AB  - Vascular surgery has evolved dramatically as a specialty, with new training
      paradigms and an ever-developing, technically demanding field. The ability to
      evaluate trainees on their fundamental skills is an important step in ensuring
      some uniformity in trainees' basic technical abilities. This article describes
      the development and implementation of the fundamentals of vascular and
      endovascular surgery, including lessons applied from the Fundamentals of
      Laparoscopic Surgery and Fundamentals of Endoscopic Surgery programs. 

PMID- 26210971
TI  - Financing a Simulation Center.
AB  - As simulation-based training has become established within medical and health
      professional disciplines, skills training laboratories have become a standard in
      surgery training programs. In 2008, the American College of Surgeons and
      Association of Program Directors in Surgery developed a simulation-based surgical
      skills curriculum; the Residency Review Committee for Surgery of the
      Accreditation Council for Graduate Medical Education mandated access to skills
      laboratories for all surgery programs. Establishing a surgical skills laboratory
      and adapting the training curriculum requires a significant amount of resources.
      This article discusses the financial aspects of establishing a training center,
      from funding opportunities to budgeting considerations. 

PMID- 26210972
TI  - Surgical Simulation Centers as Educational Homes for Practicing Surgeons.
AB  - Given the pace of change in surgery today and a growing need to decrease
      variability in the delivery of health care to optimize quality while minimizing
      cost, surgeons need an "educational home" where they can return to intermittently
      through their career to retool. We need as robust of an educational structure to
      support practicing surgeons as we have for students and postgraduate trainees. 

PMID- 26210973
TI  - Advanced Engineering Technology for Measuring Performance.
AB  - The demand for competency-based assessments in surgical training is growing. Use
      of advanced engineering technology for clinical skills assessment allows for
      objective measures of hands-on performance. Clinical performance can be assessed
      in several ways via quantification of an assessee's hand movements (motion
      tracking), direction of visual attention (eye tracking), levels of stress
      (physiologic marker measurements), and location and pressure of palpation (force
      measurements). Innovations in video recording technology and qualitative analysis
      tools allow for a combination of observer- and technology-based assessments.
      Overall the goal is to create better assessments of surgical performance with
      robust validity evidence. 

PMID- 26210974
TI  - Moving the Needle: Simulation's Impact on Patient Outcomes.
AB  - This review investigates the available literature that addresses the impact
      simulator training has on patient outcomes. The authors conducted a comprehensive
      literature search of studies reporting outcomes of simulation training and
      categorized studies based on the Kirkpatrick model of training evaluation.
      Kirkpatrick level 4 studies reporting patient outcomes were identified and
      included in this review. Existing evidence is promising, demonstrating patient
      benefits as a result of simulation training for central line placement, obstetric
      emergencies, cataract surgery, laparoscopic inguinal hernia repair, and team
      training. 

PMID- 26210975
TI  - Conducting Elite Performance Training.
AB  - Training to excellence in the conduct of surgical procedures has many
      similarities to the acquisition and mastery of technical skills in elite-level
      music and sports. By using coaching techniques and strategies gleaned from
      analysis of professional music ensembles and athletic training, surgical
      educators can set conditions that increase the success rate of training to elite
      performance. This article describes techniques and strategies used in both music
      and athletic coaching, and it discusses how they can be applied and integrated
      into surgical simulation and education. 

PMID- 26210976
TI  - Emotional Intelligence and Simulation.
AB  - Emotional intelligence (EI) is an established concept in the business literature
      with evidence that it is an important factor in determining career achievement.
      There is increasing interest in the role that EI has in medical training, but it
      is still a nascent field. This article reviews the EI literature most relevant to
      surgical training and proposes that simulation offers many benefits to the
      development of EI. Although there are many unanswered questions, it is expected
      that future research will demonstrate the effectiveness of using simulation to
      develop EI within surgery. 

PMID- 26210977
TI  - Advances in Teaching and Assessing Nontechnical Skills.
AB  - The importance of surgeons' nontechnical skills is gaining widespread recognition
      as a critical element of high-quality and safe surgical care. This article
      reviews the knowledge base on training and assessing surgeons, and operating room
      (OR) teams, in nontechnical aspects of their performance. Nontechnical skills are
      defined in the context of the OR and key assessment instruments that have been
      developed to capture these skills are reviewed. Key developments that have taken
      place in the past decade on formal skills training are discussed, and
      recommendations to further advance nontechnical skills and team-based training
      and assessment in surgery are presented. 

PMID- 26210978
TI  - Using Simulation to Improve Systems.
AB  - Simulation technology provides an important opportunity to prospectively identify
      systemic problems with minimal risk to patient safety and quality. Health care
      systems are implementing simulation-based exercises on a more regular basis,
      especially in high-risk settings such as the emergency department and operating
      room. The adoption of simulation-based and other system-oriented improvement
      strategies by the health care industry, especially regarding quality and safety,
      was preceded by its development in the manufacturing and aviation sectors. 

PMID- 26210979
TI  - Simulation for Maintenance of Certification.
AB  - Maintenance of certification (MOC) is a process through which practitioners are
      able to show continuing competence in their areas of expertise. Simulation plays
      an increasingly important role in the assessment of students and residents, as
      well as in the initial practice certification for health care professionals. The
      use of simulation as an assessment tool in MOC has been sluggish to be
      universally accepted. This article discusses the role of simulation in health
      care education, how simulation might be effectively applied in the MOC process,
      and the future role of simulation in the MOC process. 

PMID- 26210980
TI  - Simulation in Surgical Training and Practice. Foreword.

PMID- 26210981
TI  - Simulation in Surgical Training and Practice. Preface.

PMID- 26210982
TI  - Impulsive synchronization of Markovian jumping randomly coupled neural networks
      with partly unknown transition probabilities via multiple integral approach.
AB  - This paper studies the impulsive synchronization of Markovian jumping randomly
      coupled neural networks with partly unknown transition probabilities via multiple
      integral approach. The array of neural networks are coupled in a random fashion
      which is governed by Bernoulli random variable. The aim of this paper is to
      obtain the synchronization criteria, which is suitable for both exactly known and
      partly unknown transition probabilities such that the coupled neural network is
      synchronized with mixed time-delay. The considered impulsive effects can be
      synchronized at partly unknown transition probabilities. Besides, a multiple
      integral approach is also proposed to strengthen the Markovian jumping randomly
      coupled neural networks with partly unknown transition probabilities. By making
      use of Kronecker product and some useful integral inequalities, a novel Lyapunov
      Krasovskii functional was designed for handling the coupled neural network with
      mixed delay and then impulsive synchronization criteria are solvable in a set of
      linear matrix inequalities. Finally, numerical examples are presented to
      illustrate the effectiveness and advantages of the theoretical results. 

PMID- 26210983
TI  - Near-Bayesian Support Vector Machines for imbalanced data classification with
      equal or unequal misclassification costs.
AB  - Support Vector Machines (SVMs) form a family of popular classifier algorithms
      originally developed to solve two-class classification problems. However, SVMs
      are likely to perform poorly in situations with data imbalance between the
      classes, particularly when the target class is under-represented. This paper
      proposes a Near-Bayesian Support Vector Machine (NBSVM) for such imbalanced
      classification problems, by combining the philosophies of decision boundary shift
      and unequal regularization costs. Based on certain assumptions which hold true
      for most real-world datasets, we use the fractions of representation from each of
      the classes, to achieve the boundary shift as well as the asymmetric
      regularization costs. The proposed approach is extended to the multi-class
      scenario and also adapted for cases with unequal misclassification costs for the
      different classes. Extensive comparison with standard SVM and some state-of-the
      art methods is furnished as a proof of the ability of the proposed approach to
      perform competitively on imbalanced datasets. A modified Sequential Minimal
      Optimization (SMO) algorithm is also presented to solve the NBSVM optimization
      problem in a computationally efficient manner. 

PMID- 26210984
TI  - Anxiety, depression, resilience and quality of life in children and adolescents
      with pre-dialysis chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a risk factor for psychosocial
      impairment and psychiatric symptoms. Children and adolescents on dialysis
      frequently have compromised daily life activities and a worse quality of life
      (QoL) compared with healthy peers. However, few studies have investigated these
      aspects of CKD in pediatric pre-dialysis CKD patients. Therefore, we have
      analyzed resilience, QoL and anxiety and depressive symptoms in children and
      adolescents with pre-dialysis CKD and compared these to the values of healthy
      controls. METHODS: Demographic and clinical data were collected from 28 children
      and adolescents with pre-dialysis CKD and 28 healthy sex- and age-matched
      controls. Psychological assessment of the participants was performed using the
      Wagnild and Young Resilience Scale, Pediatric Quality of Life (QoL) Inventory 4.0
      , Child Depression Inventory and Self-report for Childhood Anxiety Related
      Disorders scales. RESULTS: Of the 56 children enrolled in our study, the CKD
      patients were referred to mental health professionals more frequently than the
      controls. Patients exhibited higher scores for separation anxiety and a higher
      frequency of clinically significant depressive symptoms. They also had lower
      overall QoL scores, as well as poorer scores for the psychological, educational
      and psychosocial subdomains of QoL instruments. There was a negative correlation
      between anxiety and depressive symptoms and all domains of QoL. Resilience was
      similar in both groups, but lower in patients with significant depressive
      symptoms. No significant association was found between clinical or laboratory
      findings and psychological variables in CKD patients. CONCLUSION: Although
      patients and controls exhibited similar scores of resilience, CKD negatively
      impacted the QoL of pediatric patients, contributing to a higher frequency of
      depression and separation anxiety.

PMID- 26210986
TI  - Energetics and mechanics of walking in patients with chronic low back pain and
      healthy matched controls.
AB  - PURPOSE: Walking in patients with chronic low back pain (cLBP) is characterized
      by motor control adaptations as a protective strategy against further injury or
      pain. The purpose of this study was to compare the preferred walking speed, the
      biomechanical and the energetic parameters of walking at different speeds between
      patients with cLBP and healthy men individually matched for age, body mass and
      height. METHODS: Energy cost of walking was assessed with a breath-by-breath gas
      analyser; mechanical and spatiotemporal parameters of walking were computed using
      two inertial sensors equipped with a triaxial accelerometer and gyroscope and
      compared in 13 men with cLBP and 13 control men (CTR) during treadmill walking at
      standard (0.83, 1.11, 1.38, 1.67 m s(-1)) and preferred (PWS) speeds. Low back
      pain intensity (visual analogue scale, cLBP only) and perceived exertion (Borg
      scale) were assessed at each walking speed. RESULTS: PWS was slower in cLBP [1.17
      (SD = 0.13) m s(-1)] than in CTR group [1.33 (SD = 0.11) m s(-1); P = 0.002]. No
      significant difference was observed between groups in mechanical work (P >=
      0.44), spatiotemporal parameters (P >= 0.16) and energy cost of walking (P >=
      0.36). At the end of the treadmill protocol, perceived exertion was significantly
      higher in cLBP [11.7 (SD = 2.4)] than in CTR group [9.9 (SD = 1.1); P = 0.01].
      Pain intensity did not significantly increase over time (P = 0.21). CONCLUSIONS:
      These results do not support the hypothesis of a less efficient walking pattern
      in patients with cLBP and imply that high walking speeds are well tolerated by
      patients with moderately disabling cLBP.

PMID- 26210987
TI  - Advancing clinical care for the patients with ketosis-prone diabetes: from
      knowledge to action.

PMID- 26210985
TI  - Prevalence, predictors, and outcomes of cardiorenal syndrome in children with
      dilated cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry.
AB  - BACKGROUND: The association of cardiorenal syndrome (CRS) with mortality in
      children with dilated cardiomyopathy (DCM) is unknown. METHODS: With a modified
      Schwartz formula, we estimated glomerular filtration rates (eGFR) for children
      >=1 year of age with DCM enrolled in the Pediatric Cardiomyopathy Registry at the
      time of DCM diagnosis and annually thereafter. CRS was defined as an eGFR of <90
      mL/min/1.73 m(2). Children with and without CRS were compared on survival and
      serum creatinine concentrations (SCr). The association between eGFR and
      echocardiographic measures was assessed with linear mixed-effects regression
      models. RESULTS: Of 285 eligible children with DCM diagnosed at >=1 year of age,
      93 were evaluable. CRS was identified in 57 of these 93 children (61.3%). Mean
      (standard deviation) eGFR was 62.0 (22.6) mL/min/1.73 m(2) for children with CRS
      and 108.0 (14.0) for those without (P < 0.001); median SCr concentrations were
      0.9 and 0.5 mg/dL, respectively (P < 0.001). The mortality hazard ratio of
      children with CRS versus those with no CRS was 2.4 (95% confidence interval 0.8
      7.4). eGFR was positively correlated with measures of left ventricular function
      and negatively correlated with age. CONCLUSIONS: CRS in children newly diagnosed
      with DCM may be associated with higher 5-year mortality. Children with DCM,
      especially those with impaired left ventricular function, should be monitored for
      renal disease.

PMID- 26210988
TI  - Theories of Lethal Mutagenesis: From Error Catastrophe to Lethal Defection.
AB  - RNA viruses get extinct in a process called lethal mutagenesis when subjected to
      an increase in their mutation rate, for instance, by the action of mutagenic
      drugs. Several approaches have been proposed to understand this phenomenon. The
      extinction of RNA viruses by increased mutational pressure was inspired by the
      concept of the error threshold. The now classic quasispecies model predicts the
      existence of a limit to the mutation rate beyond which the genetic information of
      the wild type could not be efficiently transmitted to the next generation. This
      limit was called the error threshold, and for mutation rates larger than this
      threshold, the quasispecies was said to enter into error catastrophe. This
      transition has been assumed to foster the extinction of the whole population.
      Alternative explanations of lethal mutagenesis have been proposed recently. In
      the first place, a distinction is made between the error threshold and the
      extinction threshold, the mutation rate beyond which a population gets extinct.
      Extinction is explained from the effect the mutation rate has, throughout the
      mutational load, on the reproductive ability of the whole population. Secondly,
      lethal defection takes also into account the effect of interactions within mutant
      spectra, which have been shown to be determinant for the understanding the
      extinction of RNA virus due to an augmented mutational pressure. Nonetheless,
      some relevant issues concerning lethal mutagenesis are not completely understood
      yet, as so survival of the flattest, i.e. the development of resistance to lethal
      mutagenesis by evolving towards mutationally more robust regions of sequence
      space, or sublethal mutagenesis, i.e., the increase of the mutation rate below
      the extinction threshold which may boost the adaptability of RNA virus,
      increasing their ability to develop resistance to drugs (including mutagens). A
      better design of antiviral therapies will still require an improvement of our
      knowledge about lethal mutagenesis. 

PMID- 26210989
TI  - Lifetime socio-economic position and depression: an analysis of the influence of
      cognitive function, behaviour and inflammatory markers.
AB  - BACKGROUND: Little is known about the influence of lifetime socio-economic
      position (SEP) on adult depression. We examined the association of SEP during the
      life course with depressive mood in late midlife and explored whether cognitive
      function at age 20, health-related behaviour and inflammatory biomarkers
      explained any associations. METHODS: A cohort of 2482 Danish men born in 1953
      with information from birth, and conscript board examinations was followed-up
      with assessment of depressive mood and blood sampling in 2010. Simple and
      multiple linear regression were used to investigate associations among variables.
      RESULTS: Social circumstances during the life course were associated with
      depressive mood. Further, low lifetime SEP was associated with lower cognitive
      score, smoking, alcohol use, high body mass index (BMI) and increased level of
      high sensitive ProReactive Protein and Interleukin-6. These covariables were also
      associated with depressive mood and when they were included into the regression
      model together with life time SEP, the beta-estimates for the latter attenuated,
      when smoking, alcohol and BMI were entered, while the inclusion of cognitive
      function and the inflammatory biomarkers had limited effect on the relation
      between lifetime SEP and depressive mood. CONCLUSIONS: Lifetime SEP was
      associated with depressive mood and health-related behaviour explained a part of
      the relation.

PMID- 26210991
TI  - Association of adiponectin and adiponectin receptor genes with sow productivity
      estimated breeding values.
AB  - Our objectives were to estimate frequencies of previously identified single
      nucleotide polymorphisms (SNPs) in adiponectin (ADIPOQ) and its receptors
      (ADIPOR1 and ADIPOR2) in a population of Duroc, Landrace and Yorkshire pigs and
      evaluate the effect of these alleles on sow productivity estimated breeding
      values (EBVs). Eight SNPs were genotyped on 446 pigs in the ADIPOQ (c.178G>A,
      c.*300A>G, c.*1094_1095insC and c.*1779A>C), ADIPOR1 (c.*129A>C) and ADIPOR2
      (c.*112G>A, c.*295G>C and c.*1455G>A) genes. Association analyses were performed
      with sow productivity EBVs based on litter records collected in Canadian breeding
      farms. There were significant associations between ADIPOQ c.178G>A and
      c.*1094_1095insC SNPs and studied traits. However, none of these associations
      remained significant after applying a Bonferroni correction. The ADIPOR2
      c.*112G>A SNP was associated with the total number of piglets born (TNB, P <
      0.001) and litter weight at weaning (LWW, P < 0.001) EBVs. Associations were also
      observed between the ADIPOR2 [A;C;G] haplotype and TNB and LWW (P < 0.001). Our
      results demonstrate that a selection in favor of the c.*112G allele or against
      the [A;C;G] haplotype may have the potential to increase LWW EBVs. However, the
      c.*112G allele is also associated with lower TNB EBVs. Some of the alleles of the
      genes studied showed substantial variability and in general, the results
      corroborated previously reported findings for an independent sow population.
      However, careful cost-benefits analyses should be performed before using these
      markers in selection program as an improvement in TNB may translate into lighter
      LWW, with its associated negative impact on production traits such as growth
      performances. 

PMID- 26210992
TI  - Allied health: integral to transforming health.
AB  - Objective South Australia is taking an innovative step in transforming the way
      its healthcare is organised and delivered to better manage current and future
      demands on the health system. In an environment of transforming health services,
      there are clear opportunities for allied health to assist in determining
      solutions to various healthcare challenges. A recent opinion piece proposed 10
      clinician-driven strategies to assist in maximising value and sustainability of
      healthcare in Australia. The present study aimed to seek the perspectives of
      allied health clinicians, educators, researchers, policy makers and managers on
      these strategies and their relevance to allied health. Methods A survey of allied
      health practitioners was undertaken to capture their perspectives on the 10
      clinician-driven strategies for maximising value and sustainability of healthcare
      in Australia. Survey findings were then layered with evidence from the
      literature. Results Highly relevant across allied health are the strategies of
      discontinuation of low value practices, targeting clinical interventions to those
      getting greatest benefit, active involvement of patients in shared decision
      making and self-management and advocating for integrated systems of care.
      Conclusions Allied health professionals have been involved in the South
      Australian healthcare system for a prolonged period, but their services are
      poorly recognised, often overlooked and not greatly supported in existing
      traditional practices. The results of the present study highlight ways in which
      healthcare services can implement strategies not only to improve the quality of
      patient outcomes, but also to offer innovative solutions for future, sustainable
      healthcare. The findings call for concerted efforts to increase the utilisation
      of allied health services to ensure the 'maximum value for spend' of the
      increasingly scarce health dollar. What is known about the topic? In medicine,
      clinician-driven strategies have been proposed to minimise inappropriate and
      costly care and maximise highly appropriate and less expensive care. These
      strategies were developed based on clinical experiences and with supporting
      evidence from scientific studies. What does this paper add? Major changes to the
      health system are required to slow down the growth in healthcare expenditure.
      This paper describes opportunities in which allied health practitioners can
      implement similar strategies not only to improve the quality of patient outcomes,
      but also to offer cost-effective solutions for a sustainable healthcare. What are
      the implications for practitioners? Allied health practitioners can provide
      solutions to healthcare challenges and assist in the transformation of healthcare
      in Australia. However, for this to happen, there should be concerted efforts to
      increase recognition of and support for the use of allied health services. 

PMID- 26210990
TI  - The unfolded protein response in neurodegenerative diseases: a neuropathological
      perspective.
AB  - The unfolded protein response (UPR) is a stress response of the endoplasmic
      reticulum (ER) to a disturbance in protein folding. The so-called ER stress
      sensors PERK, IRE1 and ATF6 play a central role in the initiation and regulation
      of the UPR. The accumulation of misfolded and aggregated proteins is a common
      characteristic of neurodegenerative diseases. With the discovery of the basic
      machinery of the UPR, the idea was born that the UPR or part of its machinery
      could be involved in neurodegenerative diseases like Alzheimer's disease,
      Parkinson's disease, amyotrophic lateral sclerosis and prion disease. Over the
      last decade, the UPR has been addressed in an increasing number of studies on
      neurodegeneration. The involvement of the UPR has been investigated in human
      neuropathology across different neurological diseases, as well as in cell and
      mouse models for neurodegeneration. Studies using different disease models
      display discrepancies on the role and function of the UPR during
      neurodegeneration, which can often be attributed to differences in methodology.
      In this review, we will address the importance of investigation of human brain
      material for the interpretation of the role of the UPR in neurological diseases.
      We will discuss evidence for UPR activation in neurodegenerative diseases, and
      the methodology to study UPR activation and its connection to brain pathology
      will be addressed. More recently, the UPR is recognized as a target for drug
      therapy for treatment and prevention of neurodegeneration, by inhibiting the
      function of specific mediators of the UPR. Several preclinical studies have shown
      a proof-of-concept for this approach targeting the machinery of UPR, in
      particular the PERK pathway, in different models for neurodegeneration and have
      yielded paradoxical results. The promises held by these observations will need
      further support by clarification of the observed differences between disease
      models, as well as increased insight obtained from human neuropathology. 

PMID- 26210993
TI  - Nuclear Mechanics and Stem Cell Differentiation.
AB  - Stem cells are characterized by their self-renewal and multi-lineage
      differentiation potential. Stem cell differentiation is a prerequisite for the
      application of stem cells in regenerative medicine and clinical therapy. In
      addition to chemical stimulation, mechanical cues play a significant role in
      regulating stem cell differentiation. The integrity of mechanical sensors is
      necessary for the ability of cells to respond to mechanical signals. The nucleus,
      the largest and stiffest cellular organelle, interacts with the cytoskeleton as a
      key mediator of cell mechanics. Nuclear mechanics are involved in the complicated
      interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem
      cell differentiation is intimately associated with nuclear mechanics due to its
      indispensable role in mechanotransduction and mechanical response. This paper
      reviews several main contributions of nuclear mechanics, highlights the hallmarks
      of the nuclear mechanics of stem cells, and provides insight into the
      relationship between nuclear mechanics and stem cell differentiation, which may
      guide clinical applications in the future.

PMID- 26210995
TI  - Novel Small Molecule Inhibitors of Cancer Stem Cell Signaling Pathways.
AB  - The main aim of oncologists worldwide is to understand and then intervene in the
      primary tumor initiation and propagation mechanisms. This is essential to allow
      targeted elimination of cancer cells without altering normal mitotic cells.
      Currently, there are two main rival theories describing the process of
      tumorigenesis. According to the Stochastic Model, potentially any cell, once
      defunct, is capable of initiating carcinogenesis. Alternatively the Cancer Stem
      Cell (CSC) Model posits that only a small fraction of undifferentiated tumor
      cells are capable of triggering carcinogenesis. Like healthy stem cells, CSCs are
      also characterized by a capacity for self-renewal and the ability to generate
      differentiated progeny, possibly mediating treatment resistance, thus leading to
      tumor recurrence and metastasis. Moreover, molecular signaling profiles are
      similar between CSCs and normal stem cells, including Wnt, Notch and Hedgehog
      pathways. Therefore, development of novel chemotherapeutic agents and proteins
      (e.g., enzymes and antibodies) specifically targeting CSCs are attractive
      pharmaceutical candidates. This article describes small molecule inhibitors of
      stem cell pathways Wnt, Notch and Hedgehog, and their recent chemotherapy
      clinical trials.

PMID- 26210996
TI  - Factors Important for Work Participation Among Older Workers with Depression,
      Cardiovascular Disease, and Osteoarthritis: A Mixed Method Study.
AB  - Purpose The aim of this study was to gain insight into differences and
      similarities in factors important for work participation in older (58-65 years)
      workers among three different chronic diseases: depression (D), cardiovascular
      disease (C), and osteoarthritis (O). Methods A mixed method design was used, with
      a qualitative part (in-depth interviews) with 14 patients with D, C or O and a
      quantitative part based on the 2002-2003 cohort of the Longitudinal Aging Study
      Amsterdam. We analysed and compared 3-year (response 93 %) predictors of paid
      work in 239 participants with D, C, or O using regression analyses. The
      qualitative findings were integrated with the quantitative findings aiming at
      complementarity. Results Common factors important for work participation were:
      working at baseline; male gender; lower age; partner with paid work; better
      physical and mental health; and higher mastery scores. The qualitative analyses
      added autonomy in work and provided contextual information regarding the
      perceived importance of working as factors important for participation in paid
      work. For D and C, work gave purpose in life and enhanced social contacts.
      Participation in work was perceived as necessary to structure life only for D.
      Conclusion Most factors important for work participation were similar for D, C,
      and O. However, the interviews revealed that for D, the context and the meaning
      attributed to these factors differed.

PMID- 26210997
TI  - Functional Restoration of Amyotrophic Lateral Sclerosis Patient-Derived
      Mesenchymal Stromal Cells Through Inhibition of DNA Methyltransferase.
AB  - Alteration of DNA methylation is highly associated with aging and
      neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS).
      Remedying these aberrant methylation patterns may serve to improve these
      diseases. Previously, we reported that human bone marrow mesenchymal stromal
      cells isolated from ALS patients (ALS-MSCs) have functionally decreased stem cell
      potency, and excessively express DNA methyltransferases (DNMTs). In this study,
      we examined the correlation between excessive DNMT expression and functional
      decline in ALS-MSCs. The DNMT inhibitor RG108 was used for this. RG108-treated
      ALS-MSCs exhibit increased expression of the anti-senescence genes TERT, VEGF,
      and ANG, and decreased expression of the senescence-related genes ATM and p21.
      The activity of SA-beta-galactosidase and the expression of senescence proteins
      p53 and p16 were reduced in RG108-treated ALS-MSCs. The abilities of cell
      migration and protection against oxidative damage were improved in the treated
      ALS-MSCs. In neuronal differentiation experiments, the treated MSCs more
      effectively differentiated into neuron-like cells. These results suggest that ALS
      MSC function can be restored by inhibiting excessively expressed DNMTs, an
      approach that may ultimately provide better efficacy in stem cell therapy. 

PMID- 26210998
TI  - Successful treatment of macrophage activation syndrome due to systemic onset
      juvenile idiopathic arthritis with antithymocyte globulin.

PMID- 26210994
TI  - The Role of Hypoxia and Cancer Stem Cells in Renal Cell Carcinoma Pathogenesis.
AB  - The cancer stem cell (CSC) model has recently been approached also in renal cell
      carcinoma (RCC). A few populations of putative renal tumor-initiating cells
      (TICs) were identified, but they are indifferently understood; however, the first
      and most thoroughly investigated are CD105-positive CSCs. The article presents a
      detailed comparison of all renal CSC-like populations identified by now as well
      as their presumable origin. Hypoxic activation of hypoxia-inducible factors
      (HIFs) contributes to tumor aggressiveness by multiple molecular pathways,
      including the governance of immature stem cell-like phenotype and related
      epithelial-to-mesenchymal transition (EMT)/de-differentiation, and, as a result,
      poor prognosis. Due to intrinsic von Hippel-Lindau protein (pVHL) loss of
      function, clear-cell RCC (ccRCC) develops unique pathological intra-cellular
      pseudo-hypoxic phenotype with a constant HIF activation, regardless of oxygen
      level. Despite satisfactory evidence concerning pseudo-hypoxia importance in RCC
      biology, its influence on putative renal CSC-like largely remains unknown. Thus,
      the article discusses a current knowledge of HIF-1alpha/2alpha signaling pathways
      in the promotion of undifferentiated tumor phenotype in general, including some
      experimental findings specific for pseudo-hypoxic ccRCC, mostly dependent from
      HIF-2alpha oncogenic functions. Existing gaps in understanding both putative
      renal CSCs and their potential connection with hypoxia need to be filled in order
      to propose breakthrough strategies for RCC treatment.

PMID- 26210999
TI  - Colchicine-clarithromycin-induced rhabdomyolysis in Familial Mediterranean Fever
      patients under treatment for Helicobacter pylori.
AB  - Chronic administration of colchicine remains a mainstay of therapy for patients
      with Familial Mediterranean Fever (FMF). As this medication is a strong CYP3A4
      inhibitor, it has the potential to interact with many routinely used medications.
      One such medication is clarithromycin, itself a strong inhibitor of the same
      enzyme, and a typical choice for triple therapy eradication of H. pylori. Various
      sequelae of colchicine-clarithromycin interaction have been documented and can be
      expected by prescribing physicians, with rhabdomyolysis, though rare, being among
      the most serious. Review of cases from a tertiary academic medical center and
      full PubMed/MEDLINE literature review. Despite the prevalence of diseases treated
      with clarithromycin and the expected drug interaction with colchicine, only two
      cases in the literature document clinical rhabdomyolysis due to colchicine
      clarithromycin interaction. In neither case, however, were patients undergoing
      treatment for FMF. Herein, we describe the first two cases in the literature of
      clinical rhabdomyolysis in FMF patients under colchicine therapy after
      administration of clarithromycin as part of therapy treating H. pylori infection.

PMID- 26211000
TI  - Population-based analysis of hospitalizations for patients with systemic
      sclerosis in a West-European region over the period 2001-2012.
AB  - The aim of this study was to evaluate systemic sclerosis (SSc) hospitalizations
      through a retrospective population-based study analyzing administrative data
      during 2001-2012 in Sardinia, an Italian region with universal Health System
      coverage. Data on hospital discharge records with ICD-9-CM code for SSc (710.1)
      were obtained from the Department of Health and Hygiene. Two-tailed Cochran
      Armitage test for trend was applied to analyze the annual trend for primary and
      non-primary discharge diagnoses. SSc prevalence was also estimated. This study
      included 4981 hospitalizations in 736 patients (84.8 % women). Hospitalizations
      with SSc as primary diagnosis were 3631 (72.9 %). Their annual number
      significantly increased during study period, from 143 in 2001 to 390 in 2012.
      Annual trend analysis revealed statistically significant increase in number and
      percentage of interstitial lung disease (p < 0.0001), pulmonary arterial
      hypertension (p < 0.0024), osteoporotic fragility fractures (p < 0.0001), ulcers,
      and gangrene (p = 0.0037) as non-primary diagnoses associated with SSc. Although
      the number of admissions with SSc as non-primary diagnosis showed a slight
      reduction during the study period, the annual number and percentage of admissions
      with respiratory failure (p = 0.0016) and congestive heart failure (p < 0.0001)
      as primary diagnosis showed a significant upward trend. Admissions for
      intravenous infusion, mainly day-hospital, accounted for 19.1 % of all
      hospitalizations for SSc and showed a significant (p = 0.0002) upward trend in
      2001-2012. The 2012 SSc prevalence in Sardinia was estimated to be 34.8 per
      100,000 inhabitants. Hospital care utilization for SSc is changing over time,
      showing increased hospitalizations aimed at the early recognition and treatment
      for the major manifestations and complications of SSc.

PMID- 26211001
TI  - Influence of type 2 diabetes on local production of inflammatory molecules in
      adults with and without chronic periodontitis: a cross-sectional study.
AB  - BACKGROUND: Pathological changes in periodontal tissues are mediated by the
      interaction between microorganisms and the host immune-inflammatory response.
      Hyperglycemia may interfere with this process. The aim of this study was to
      compare the levels of 27 inflammatory molecules in the gingival crevicular fluid
      (GCF) of patients with type 2 diabetes, with and without chronic periodontitis,
      and of chronic periodontitis subjects without diabetes. A putative correlation
      between glycated haemoglobin (HbA1c) and levels of the inflammatory molecules was
      also investigated. METHODS: The study population comprised a total of 108
      individuals, stratified into: 54 with type 2 diabetes and chronic periodontitis
      (DM + CP), 30 with chronic periodontitis (CP) and 24 with type 2 diabetes (DM).
      Participants were interviewed with the aid of structured questionnaire.
      Periodontal parameters (dental plaque, bleeding on probing and periodontal pocket
      depth) were recorded. The GCF levels of the 27 inflammatory molecules were
      measured using multiplex micro-bead immunoassay. A glycated haemoglobin (HbA1c)
      test was performed for patients with diabetes by boronate affinity
      chromatography. RESULTS: After adjustment for potential confounders, the DM + CP
      group had higher levels of IL-8 and MIP-1beta, and lower levels of TNF-alpha, IL
      4, INF-gamma, RANTES and IL-7 compared to the CP group. Moreover, the DM + CP
      group had lower levels of IL-6, IL-7 and G-CSF compared to the DM group. The DM
      group had higher levels of IL-10, VEGF, and G-CSF compared to the CP group. The
      levels of MIP-1alpha and FGF were lower in diabetes patients (regardless of their
      periodontal status) than in chronic periodontitis subjects without diabetes.
      Diabetes patients (DM + CP and DM) had higher Th-2/Th-1 ratio compared to the CP
      group. HbA1c correlated positively with the pro-inflammatory cytokines (Pearson
      correlation coefficient = 0.27, P value: 0.02). CONCLUSION: Type 2 diabetes and
      chronic periodontitis may influence the GCF levels of inflammatory molecules
      synergistically as well as independently. Type 2 diabetes was associated with
      high Th-2/Th-1 ratio, and modulated the local expression of molecules involved in
      the anti-inflammatory and healing processes.

PMID- 26211003
TI  - Extracorporeal shock wave lithotripsy versus retrograde intrarenal surgery for
      treatment for renal stones 1-2 cm: a meta-analysis.
AB  - This study is to evaluate the efficacy and safety of extracorporeal shock wave
      lithotripsy (ESWL) versus retrograde intrarenal surgery (RIRS) for the treatment
      for renal calculi 1-2 cm. PubMed, Embase, the Cochrane Central Register of
      Controlled Trials, and the Chinese Biomedical Literature Database were researched
      and hand-searched for relevant congress abstracts and journals about RIRS and
      ESWL for the treatment for 1- to 2-cm renal stones. The retrieval time ended in
      September 2014. The related trials met the inclusion criteria were included in
      the meta-analysis. Two reviewers independently assessed the quality of all
      included studies, and meta-analysis was performed with RevMan 5.2. Seven
      literatures were retrieved, including 983 patients. The meta-analysis results
      showed that, compared to RIRS group, the patients in ESWL group had the following
      features:(1) the stone-free rate [relative risk (RR) 0.86; 95% confidence
      interval (CI) 0.77-0.95, P = 0.005] was significantly different between two
      groups; (2) The retreatment rate of RIRS group was lower (RR 8.12; 95% CI 4.77
      13.83, P < 0.00); (3) The complications were not significantly different between
      two groups (Grade I RR 1.06; 95% CI 0.67-1.69, P = 0.80; Grade II RR 0.75; 95% CI
      0.29-1.91, P = 0.54; Grade III RR 0.86; 95% CI 0.26-2.86, P = 0.80). Compared to
      ESWL, our results showed that RIRS provided significantly higher stone-free rate
      and lower retreatment rate and without increase in the incidence of
      complications. However, further randomized trials are needed to confirm these
      findings.

PMID- 26211002
TI  - Acupuncture for chronic fatigue syndrome and idiopathic chronic fatigue: a
      multicenter, nonblinded, randomized controlled trial.
AB  - BACKGROUND: The causes of chronic fatigue syndrome (CFS) and idiopathic chronic
      fatigue (ICF) are not clearly known, and there are no definitive treatments for
      them. Therefore, patients with CFS and ICF are interested in Oriental medicine or
      complementary and alternative medicine. For this reason, the effectiveness of
      complementary and alternative treatments should be verified. We investigated the
      effectiveness of two forms of acupuncture added to usual care for CFS and ICF
      compared to usual care alone. METHODS: A three-arm parallel, non-blinded,
      randomized controlled trial was performed in four hospitals. We divided 150
      participants into treatment and control groups at the same ratio. The treatment
      groups (Group A, body acupuncture; Group B, Sa-am acupuncture) received 10
      sessions for 4 weeks. The control group (Group C) continued usual care alone. The
      primary outcome was the Fatigue Severity Scale (FSS) at 5 weeks after
      randomization. Secondary outcomes were the FSS at 13 weeks and a short form of
      the Stress Response Inventory (SRI), the Beck Depression Inventory (BDI), the
      Numeric Rating Scale (NRS), and the EuroQol-5 Dimension (EQ-5D) at 5 and 13
      weeks. RESULTS: Group A showed significantly lower FSS scores than Group C at 5
      weeks (P = 0.023). SRI scores were significantly lower in the treatment groups
      than in the control group at 5 (Group A, P = 0.032; B, P <0.001) and 13 weeks
      (Group A, P = 0.037; B, P <0.001). Group B showed significantly lower BDI scores
      than Group C at 13 weeks (P = 0.007). NRS scores from the treatment groups were
      significantly reduced compared to control at 5 (Group A and B, P <0.001) and 13
      weeks (Group A, P = 0.011; B, P = 0.002). CONCLUSIONS: Body acupuncture for 4
      weeks in addition to usual care may help improve fatigue in CFS and ICF patients.
      TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0000508;
      Registered on 12 August 2012.

PMID- 26211004
TI  - Delivery of miR-155 to retinal pigment epithelial cells mediated by Burkitt's
      lymphoma exosomes.
AB  - Exosomes are extracellularly secreted vesicles ranging from 40 to 100 nm in
      diameter that are thought to play important roles in intercellular communication.
      Exosomes contain numerous proteins, RNA, and lipids that can affect the status of
      recipient cells under various pathological conditions. MicroRNAs (miRNAs) are
      small non-coding RNAs that play a major role in post-transcriptional gene
      silencing by interacting with the 3'-untranslated regions of target genes.
      Epstein-Barr virus (EBV) has been reported to induce sustained elevation of
      cellular miRNAs such as miR-155. We hypothesized that miRNAs delivered by
      exosomes might affect the angiogenesis of retinal pigment epithelial (RPE) cells.
      Here, we demonstrated that co-culture of EBV-positive Burkitt's lymphoma (BL)
      cells (Raji) with retinal pigment epithelial (ARPE-19) cells increased the level
      of miR-155 in recipient cells whereas no major difference was detected for co
      culture with EBV-negative BL cells (Ramos). Isolated Raji exosomes increased
      transcriptional and translational levels of VEGF-A in ARPE-19 cells, which was
      reversely correlated with von Hippel-Lindau expression. A human umbilical vein
      endothelial cell tube formation assay showed that delivery of ectopic miR-155
      rendered ARPE-19 cells proangiogenic. Our results demonstrate that sustained
      accumulation of miR-155 mediated by exosomes might affect remote recipient cells
      such as retinal pigment epithelial cells. 

PMID- 26211005
TI  - Retinoic acid morpholine amide (RAMA) inhibits expression of Fas ligand through
      EP1 receptor in colon cancer cells.
AB  - Among the members of tumour necrosis factor family Fas ligand on binding to its
      receptor strongly induces apoptosis of tumour-infiltrating lymphocytes (TIL).
      Thus, FasL acts as an inhibitor of anti-tumour immune response. The present study
      demonstrates that retinoic acid morpholine amide (RAMA) significantly suppresses
      FasL expression in colon cancer cells in a dose- and time-dependent manner. The
      suppression of FasL mRNA and proteins was significant at a concentration of 30
      MUM after 48 h in CLT85 and HT26 colon cancer cells. There was around 2.6- and
      3.2-fold decrease in FasL mRNA after incubation with 30 MUM of RAMA in CLT85
      cells and HT26 cells, respectively. The results from Western blot showed a
      decrease in FasL mRNA and protein expression in both CLT85 and HT26 cells after
      suppression of cyclooxygenase (COX)-2 and COX-1 by RNAi. However, when COX-2
      specific silencer RNA (siCOX-2)- and siCOX-1-treated CLT85 and HT26 cells were
      exposed to RAMA, inhibition of FasL expression was further suppressed. The siCOX
      2-treated CLT85 and HT26 cells on exposure to RAMA showed ~87 and ~54 % reduction
      in FasL mRNA, respectively. Co-culture of Jurkat T cells with RAMA-treated HT26
      and CLT85 cells decreased the viability of Jurkat T cells by only 2 and 4.3 %,
      respectively, compared to 19.5 and 37.3 % in control HT26 and CLT85 cells. The
      results from real-time reverse transcription polymerase chain reaction (RT-PCR)
      and immunoblotting showed that suppression of EP1 prevented RAMA-induced FasL
      suppression in CLT85 cells at both the mRNA and protein levels. Thus, RAMA can be
      a potent therapeutic agent for the treatment of colon tumours. 

PMID- 26211006
TI  - Multifocal soft tissue Langerhans' cell histiocytosis treated with PET-CT based
      conformal radiotherapy.
AB  - INTRODUCTION: Langerhans' cell histiocytosis (LCH) is a proliferative disorder of
      Langerhans cells, which is seen extremely rarely in adults. Conventional imaging
      modalities, such as skeletal surveys and bone scans, were accepted to be standard
      methods for diagnosis; however, 18-fluorodeoxyglucose positron emission
      tomography (PET-CT) has been increasingly used. METHODS: We report on a 33-year
      old female patient with disseminated LCH treated with radiotherapy and systemic
      chemotherapy where PET-CT has been used for defining the extent of the disease,
      RT planning and assessment of treatment response during follow-up. RESULTS: The
      patient was treated with 24 Gy 3-dimensional conformal radiotherapy (RT), given
      as 2 Gy a day, 5 days a week. The patient was also treated with systemic
      prednisolone 20 mg/m(2), concurrently. The chemotherapeutic regimen switched to
      cytosine-arabinoside with a dose of 100 mg/m(2) subcutaneously daily for 4 days,
      vincristine 1.5 mg/m(2) given on the 1st day and prednisolone 20 mg/m(2) for 4
      cycles. After local RT with adjuvant chemotherapy, the patient was alive for 54
      months and remained disease-free at last visit. CONCLUSION: RT is a treatment
      choice in multi-system LCH as well as solitary lesions. Low-dose RT is adequate
      to control large masses of LCH including soft tissue and lymph nodes.

PMID- 26211007
TI  - College Students With Asthma: The Perfect Storm.

PMID- 26211008
TI  - Weakness and Fluid Overload Hinder Weaning. Or Do They?

PMID- 26211009
TI  - Seriously, Should We Be Treating Severe ARDS With High-Flow Nasal Cannula Oxygen?

PMID- 26211010
TI  - Seriously, Should We Be Treating Severe ARDS With High-Flow Nasal Cannula Oxygen?
      -Reply.

PMID- 26211011
TI  - CORRECTION.

PMID- 26211013
TI  - Non-vascular interventional procedures: effective dose to patient and equivalent
      dose to abdominal organs by means of DICOM images and Monte Carlo simulation.
AB  - This study evaluates X-ray exposure in patient undergoing abdominal extra
      vascular interventional procedures by means of Digital Imaging and COmmunications
      in Medicine (DICOM) image headers and Monte Carlo simulation. The main aim was to
      assess the effective and equivalent doses, under the hypothesis of their
      correlation with the dose area product (DAP) measured during each examination.
      This allows to collect dosimetric information about each patient and to evaluate
      associated risks without resorting to in vivo dosimetry. The dose calculation was
      performed in 79 procedures through the Monte Carlo simulator PCXMC (A PC-based
      Monte Carlo program for calculating patient doses in medical X-ray examinations),
      by using the real geometrical and dosimetric irradiation conditions,
      automatically extracted from DICOM headers. The DAP measurements were also
      validated by using thermoluminescent dosemeters on an anthropomorphic phantom.
      The expected linear correlation between effective doses and DAP was confirmed
      with an R(2) of 0.974. Moreover, in order to easily calculate patient doses,
      conversion coefficients that relate equivalent doses to measurable quantities,
      such as DAP, were obtained. 

PMID- 26211014
TI  - Interpersonal brain synchronization in the right temporo-parietal junction during
      face-to-face economic exchange.
AB  - In daily life, interpersonal interactions are influenced by uncertainty about
      other people's intentions. Face-to-face (FF) interaction reduces such uncertainty
      by providing external visible cues such as facial expression or body gestures and
      facilitates shared intentionality to promote belief of cooperative decisions and
      actual cooperative behaviors in interaction. However, so far little is known
      about interpersonal brain synchronization between two people engaged in naturally
      occurring FF interactions. In this study, we combined an adapted ultimatum game
      with functional near-infrared spectroscopy (fNIRS) hyperscanning to investigate
      how FF interaction impacts interpersonal brain synchronization during economic
      exchange. Pairs of strangers interacted repeatedly either FF or face-blocked
      (FB), while their activation was simultaneously measured in the right temporo
      parietal junction (rTPJ) and the control region, right dorsolateral prefrontal
      cortex (rDLPFC). Behaviorally, FF interactions increased shared intentionality
      between strangers, leading more positive belief of cooperative decisions and more
      actual gains in the game. FNIRS results indicated increased interpersonal brain
      synchronizations during FF interactions in rTPJ (but not in rDLPFC) with greater
      shared intentionality between partners. These results highlighted the importance
      of rTPJ in collaborative social interactions during FF economic exchange and
      warrant future research that combines FF interactions with fNIRS hyperscanning to
      study social brain disorders such as autism. 

PMID- 26211017
TI  - Protect your vision to protect your independence.  Comprehensive exams and
      preventive care are the keys to eye health.

PMID- 26211016
TI  - Genetic diversity of wild-type measles viruses and the global measles nucleotide
      surveillance database (MeaNS).

PMID- 26211015
TI  - Theory of mind and empathy in preclinical and clinical Huntington's disease.
AB  - We investigated cognitive and affective Theory of Mind (ToM) and empathy in
      patients with premanifest and manifest Huntington's disease (HD). The
      relationship between ToM performance and executive skills was also examined.
      Sixteen preclinical and 23 clinical HD patients, and 39 healthy subjects divided
      into 2 control groups were given a French adaptation of the Yoni test (Shamay
      Tsoory, S.G., Aharon-Peretz, J. (2007). Dissociable prefrontal networks for
      cognitive and affective theory of mind: a lesion study. Neuropsychologia, 45(3),
      3054-67) that examines first- and second-order cognitive and affective ToM
      processing in separate conditions with a physical control condition. Participants
      were also given questionnaires of empathy and cognitive tests which mainly
      assessed executive functions (inhibition and mental flexibility). Clinical HD
      patients made significantly more errors than their controls in the first- and
      second-order cognitive and affective ToM conditions of the Yoni task, but
      exhibited no empathy deficits. However, there was no evidence that ToM impairment
      was related to cognitive deficits in these patients. Preclinical HD patients were
      unimpaired in ToM tasks and empathy measures compared with their controls. Our
      results are consistent with the idea that impaired affective and cognitive
      mentalizing emerges with the clinical manifestation of HD, but is not necessarily
      part of the preclinical stage. Furthermore, these impairments appear independent
      of executive dysfunction and empathy. 

PMID- 26211019
TI  - Reduce your risk of silent strokes.  Exercise, eat a healthy diet, and manage
      blood pressure and cholesterol to lower your odds.

PMID- 26211018
TI  - Ask the doctor.  Do the protective effects of alcohol extend to dessert wines and
      liqueurs, or do those have too much sugar?

PMID- 26211020
TI  - Safe exercise:  know the warning signs of pushing too hard.  Chest pain,
      dizziness, and shortness of breath mean you should back off and call your doctor.

PMID- 26211021
TI  - Boost the power of your cereal.  Learn which ingredients will give your day a
      healthy start.

PMID- 26211022
TI  - Stay a step ahead of urinary tract infections.  Keep hydrated, and empty your
      bladder often to stave off these risky infections.

PMID- 26211023
TI  - Tips to help the medicine go down.  Adding medications to foods and trying new
      swallowing techniques can help.

PMID- 26211024
TI  - Obituary. John Roberts, 1942-2015.

PMID- 26211025
TI  - Add weight training to control belly fat, say Harvard researchers.

PMID- 26211026
TI  - Balance and strength exercises may help reduce falls.

PMID- 26211027
TI  - Poor sleep linked to dementia and ministrokes.

PMID- 26211028
TI  - I. K. Brunel's Crimean War Hospital. Re: Crimean Mortality, Florence Nightingale
      and Mary Seacole.

PMID- 26211029
TI  - In response to Dr Trubuhovich.

PMID- 26211030
TI  - Contact lens-assisted corneal cross-linking.

PMID- 26211031
TI  - Primary Care Teams, Composition, Roles, and  Satisfaction of PA Students During
      Primary  Care Rotations.
AB  - PURPOSE: The goal of t his study was to describe the characteristics of primary
      care teams, activities, and ro les of physician assistant (PA) students as they
      encounter various primary care sites. METHODS: An electronic survey was
      distributed to second year PA students in 12 programs who had completed at least
      4 weeks in a primary care rotation. RESULTS: Of the 179 students who responded
      (response rate 41 %), 88% had completed their primary care rotations in urban
      settings, mostly in private practices (53%). Physician assistant students
      reported encountering many types of health care providers on their teams, and the
      2 most favored features of the rotations were the interactions with their
      supervising clinicians and clinical responsibilities. About 68% interacted with
      other health profession students during their rotation(interprofessional
      experiential learning). Almost all students completed histories, physical
      examinations, and treatment plans, but less than 30% reported involvement in
      billing or care coordination and less than 10% participated in quality
      improvement projects. More than 60% were satisfied with team-based and
      interprofessional practices encountered during their primary care rotations, and
      39% were more than likely to pursue primary care careers. CONCLUSIONS: Team-based
      prima ry ca re had a positive impact on students, but more exposure to
      underserved clinical settings, care coordination, quality improvement, and
      billing is needed to prepare PA students for the practice of the future. This
      study is t he first of its kind to explore the relationship between primary care
      sites and PA training in the era of health care reform.

PMID- 26211033
TI  - Predictors of Student Success on the Physician Assistant National Certifying
      Examination: Erratum.

PMID- 26211032
TI  - Empathy Between Physician Assistant Students and Standardized Patients: Evidence
      of an Inflation Bias.
AB  - PURPOSE: Empathic communication with patients is an essential component of
      quality primary care. This study examines the ability of physician assistant (PA)
      students to communicate empathically in clinical interviews with standardized
      patients. METHODS: In their first year of training, PA students conducted 3
      clinical interviews with standardized patients over a 6-month period in 2014,
      during the second half of their didactic year. Each interview was evaluated for
      empathy by 4 individuals: the students themselves, their standardized patients,
      their clinical instructors, and third-party observers. RESULTS: Students
      consistently rated their empathic abilities more favorably than did patients,
      clinical instructors, or observers, with mean differences ranging from 0.56 to
      1.92 and averaging 1.09 on a 9-point scale. Students' evaluations were most
      dissimilar from those of patients (difference M = 1.12) and most similar to those
      of observers (difference M = 1.06). The assessments of all 4 raters varied over
      time: students rated themselves as significantly more empathic in April (time 2)
      than in July (time 3) of their didactic year. Patients rated students as
      significantly less empathic in January of the didactic year (time 1) than at time
      2 and as significantly more empathic at time 2 than time 3. Instructors rated
      students as significantly less empathic at time 1 than at either time 2 or time
      3. Finally, observers rated students as significantly more empathic at time 1
      than at either time 2 or time 3. CONCLUSIONS: PA students consistently
      overestimate their empathic abilities during their first year of training. Given
      the importance of empathy in clinical care, increased didactic efforts focused on
      developing and conveying empathy may be warranted in PA education.

PMID- 26211034
TI  - A postcard from Bhutan--AHA spreads the biosecurity message.

PMID- 26211035
TI  - Our Australian Cattle Vets raise the bar.

PMID- 26211036
TI  - VET SOS.

PMID- 26211037
TI  - Vet incomes just above CPI.

PMID- 26211038
TI  - Global outreach in South Africa.

PMID- 26211039
TI  - Deaths in Bellinger River snapping turtles.

PMID- 26211040
TI  - Work-life balance.

PMID- 26211041
TI  - Livestock outbreak helps to unlock liver condition.

PMID- 26211042
TI  - Veterinary Workforce Survey 2014 released.

PMID- 26211043
TI  - [Storage and allocation of carbon and nitrogen in Pinus tabuliformis plantations
      on the south slope of the East Qinling Mountains, China].
AB  - The objective of this study was to study carbon and nitrogen storages and
      distributions in Pinus tabuliformis plantations along an age chronosequence of 8
      , 25-, 35-, 42- and 61-year-old on the south slope of the East Qinling Mountains;
      China. Results showed that the carbon content and nitrogen contents ranged from
      441.40 to 526.21 g . kg-1 and from 3.13 to 3.99 g . kg-1 in arbor layer, from
      426.06 to 447.25 g . kg-1 and from 10.62 to 12.45 g . kg-1 in shrub layer, from
      301.37 to 401.52 g . kg-1 and from 10.35 to 13.33 g kg-1 in herb layer, from
      382.83 to 424.71 g . kg-1, and from 8.69 to 11.90 g . kg-1 in litter layer, and
      from 1.51 to 18.17 g . kg-1 and from 0.29 to 1.45 g . kg-1 in soil layer (0-100
      cm) , respectively. The largest carbon and nitrogen storages in arbor layer were
      trunks and branches, which made up 48.5% to 62.7% and 39.2% to 48.4% of the total
      storage, respectively. Carbon and nitrogen storages of P. tabuliformis
      plantations were obviously age-dependent. Carbon storage at first increased with
      stand Age before the stand was ripe. It was the highest (146.06 t . hm-2) when
      the stand was 35 year-old, after which the carbon storage de- creased. The
      nitrogen storage reached the peak value of 10.99 t . hm-2 at 25 year-old. The
      average carbon and nitrogen storages were 45.33 t . hm-2 and 568.55 kg . hm-2 in
      the plant layer and, 73.12 and 8.57 t . hm-2 in soil layer, respectively.
      Moreover, carbon and nitrogen were accumulated at higher levels in the surface
      soil layer. In addition, the storages of carbon and nitrogen were mainly
      distributed in soil layer and arbor layer in this region. The average carbon
      storage in different components followed an order as soil layer (64.1%) > arbor
      layer (30.0%) > shrub-herb and litter layers (5.9%), while the nitrogen storage
      followed as: soil layer (93.2%) > arbor layer (5.3%) > shrub-herb and litter
      layers (1.5%).

PMID- 26211044
TI  - [Characteristics of 'salt island' and 'fertile island' for Tamarix chinensis and
      soil carbon, nitrogen and phosphorus ecological stoichiometry in saline-alkali
      land].
AB  - To clarify the nutrient characteristics of 'salt island' and 'fertile island'
      effects in saline-alkali soil, the native Tamarix chinensis of the Yellow River
      Delta (YRD) was selected to measure its soil pH, electrical conductivity (EC),
      organic carbon (SOC), total nitrogen (N), total phosphorus (P) and their
      stoichiometry characteristics at different soil depths. The results showed that
      soil pH and EC increased with the increasing soil depth. Soil EC and P in the 0
      20 cm layer decreased and increased from canopied area to interspace,
      respectively. SOC, N, N/P and C/P in the 20-40 cm soil layer decreased, and C/N
      increased from the shrub center to interspace. SOC and N contents between island
      and interspace both decreased but P content decreased firstly and then increased
      with the increasing soil depth. Soil pH correlated positively with EC. In
      addition, pH and EC correlated negatively with C, N, P contents and their
      ecological stoichiometry.

PMID- 26211045
TI  - [Leaf and soil stoichiometry of four herbs in the Gurbantunggut Desert, China].
AB  - The leaf and soil stoichiometric characteristics and their relationships of two
      ephemeral plants (Hypecoum erectum and Euphorbia turczaninowii) and two
      ephemeroid plants (Ferula meyeri and Astragalus flexus) were analyzed in extreme
      desert environment. There was no significant difference among each soil factor in
      different sampling plots of each species. Soil nitrogen (N) content (0.18-0.22 mg
      . g-1) was far lower than soil phosphorus (P) content (1.58-1.62 mg . g-1), and
      the N/P only ranged 0.12-0.15, indicating a serious lack of soil N. N, P and N/P
      all represented significant difference among the four species, in which A. flexus
      had the highest values with 57.36 mg . g-1, 2.46 mg . g-1 and 23.43, followed by
      H. erectum with 34.05 mg . g-1, 1.98 mg . g-1 and 17.56, the values for E.
      turczaninowii were 27.07 mg . g-1, 1.87 mg . g-1 and 14.51, and the values for F.
      meyeri were 28.63 mg . g-1, 2.20 mg . g-1 and 13.10, respectively. N and P
      contents showed significant correlation of each species, while most soil factors
      did not show significant correlation with leaf stoichiometric values.

PMID- 26211046
TI  - [Effects of understory removal on soil greenhouse gas emissions in Carya
      cathayensis stands].
AB  - CO2, N2O and CH4 are important greenhouse gases, and soils in forest ecosystems
      are their important sources. Carya cathayensis is a unique tree species with
      seeds used for high-grade dry fruit and oil production. Understory vegetation
      management plays an important role in soil greenhouse gases emission of Carya
      cathayensis stands. A one-year in situ experiment was conducted to study the
      effects of understory removal on soil CO2, N2O and CH4 emissions in C.
      cathayensis plantation by closed static chamber technique and gas chromatography
      method. Soil CO2 flux had a similar seasonal trend in the understory removal and
      preservation treatments, which was high in summer and autumn, and low in winter
      and spring. N2O emission occurred mainly in summer, while CH4 emission showed no
      seasonal trend. Understory removal significantly decreased soil CO, emission,
      increased N2O emission and CH4 uptake, but had no significant effect on soil
      water soluble organic carbon and microbial biomass carbon. The global warming
      potential of soil greenhouse gases emitted in the understory removal. treatment
      was 15.12 t CO2-e . hm-2 a-1, which was significantly lower than that in
      understory preservation treatment (17.04 t CO2-e . hm-2 . a-1).

PMID- 26211047
TI  - [Adaptability of mangrove Kandelia obovata seedlings to salinity-waterlogging].
AB  - A laboratory test on the effects of 12 salinity-waterlogging stresses on the
      growth of Kandelia obovata seedlings was conducted. Nine growth indexes including
      seedling height, stem height, basal diameter, node number, leaf number, root
      biomass, stem biomass, leaf biomass and total biomass were measured. The results
      showed that salinity and salinity-waterlogging stresses had significant effects
      on the growth of K. obovata seedlings, while waterlogging stress had no
      significant effects on the seedling height, stem height, basal diameter, node
      number and leaf number, but had significant effects on root biomass, stem
      biomass, leaf biomass and total biomass. The growth and biomass of K. obovata
      seedlings decreased with increasing the salinity and waterlogging time. The
      principal components analysis showed that K. obovata seedlings would grow best
      under the 7 per thousand salinity+2 h waterlogging stress, while the 21per
      thousand+8 h combination was a critical stress.

PMID- 26211048
TI  - [Spatial-temporal characteristics of land surface temperature in Tianshan
      Mountains area based on MODIS data].
AB  - Based on the MODIS/MOD11A2 data from 2001 to 2013, this paper researched the
      characteristics of land surface temperature (LST) of Tianshan Mountains area. The
      results indicated that the average of LST in the study area was 1.73  degrees C ,
      and LST was much higher in the east than in the west. The inter-annual variation
      range of LST in the northwest was significantly large than in other regions, with
      the largest above 0.55  degrees C in some areas. The LST tended to slowly
      increase with time, and the increase rate was 0.147  degrees C . a-1. It showed a
      significant seasonal difference, and the fluctuation of winter was significantly
      larger than in other seasons with the coefficient of variation reaching 12.7%.
      The LST difference of day time was greater than that at night, and that in summer
      was greater than in other seasons. The LST differed with land use types, and the
      fitted results were inconsistent between the LST and NDVI. With the increase of
      NDVI of woodland and grassland, the LST decreased dramatically. The LST of
      construction land and cropland under the influence of human activities had higher
      sensitivity with NDVI than other land types.

PMID- 26211049
TI  - [Growth response of Abies fargesii to climate in Shennongjia Mount of Hubei
      Province, Southeastern China].
AB  - A well-replicated Abies fargesii tree-ring width chronology in the Shennongjia
      Mount was developed to investigate its radial growth response to climate
      variables (e.g., monthly mean tempe- rature and total precipitation) and other
      growing season indicators (e.g., cumulative temperature, continuous days, initial
      and final dates). Correlation analyses showed that the tree-ring width was
      positively correlated to the mean temperatures of February, April and September,
      and negatively correlated to the total precipitation of September, prior
      September and prior December. The analyses between the chronology and other
      growing season parameters showed that tree growth responded positively to the
      cumulative temperature and continuous days of the growing season. The correlation
      was the highest when the growing season was defined as the days above the
      temperature threshold of 9.0  degrees C. Defined this way, the growing season
      typically started in late-May and ended in mid-September, lasting about 120 days.
      Correlation analyses were also conducted between the tree-ring growth and the
      initial and final dates of the growing season. Results showed that correlation
      was the highest for initial dates defined at 9.0  degrees C (with the coefficient
      of -0.25 and p-value close to 0.05), and for final dates defined at 9.3  degrees
      C (with the coefficient of 0.33 and p-value less than 0.05). All these results
      indicated that the sensitive temperature threshold for photosynthesis of A.
      fargesii was around 9.0  degrees C. The year 1978 marked an abrupt shift of
      climate in southeast China. We compared A. fargesii growth between pre-1978 and
      post-1978 periods. Results showed that as temperature rose, the growing season
      was lengthened with both earlier initial dates and later final dates. Longer
      growing season increased the A. fargesii growth in the Shennongjia Mount,
      southeastern China.

PMID- 26211050
TI  - [Error structure and additivity of individual tree biomass model for four natural
      conifer species in Northeast China].
AB  - Based on the biomass data of 276 sampling trees of Pinus koraiensis, Abies
      nephrolepis, Picea koraiensis and Larix gmelinii, the mono-element and dual
      element additive system of biomass equations for the four conifer species was
      developed. The model error structure (additive vs. multiplicative) of the
      allometric equation was evaluated using the likelihood analysis, while nonlinear
      seemly unrelated regression was used to estimate the parameters in the additive
      system of biomass equations. The results indicated that the assumption of
      multiplicative error structure was strongly supported for the biomass equations
      of total and tree components for the four conifer species. Thus, the additive
      system of log-transformed biomass equations was developed. The adjusted
      coefficient of determination (Ra 2) of the additive system of biomass equations
      for the four conifer species was 0.85-0.99, the mean relative error was between 
      7.7% and 5.5%, and the mean absolute relative error was less than 30.5%. Adding
      total tree height in the additive systems of biomass equations could
      significantly improve model fitting performance and predicting precision, and the
      biomass equations of total, aboveground and stem were better than biomass
      equations of root, branch, foliage and crown. The precision of each biomass
      equation in the additive system varied from 77.0% to 99.7% with a mean value of
      92.3% that would be suitable for predicting the biomass of the four natural
      conifer species.

PMID- 26211051
TI  - [Responses of soil microbial carbon metabolism to the leaf litter composition in
      Liaohe River Nature Reserve of northern Hebei Province, China].
AB  - Using litter bag method, we studied the effects of single and mixed litters from
      Betula platyphlla, Populus davidiana and Quercus mongolica on soil microbial
      biomass carbon (MBC), microbial respiration (MR) and microbial metabolic quotient
      (qCO2) in 0-5, 5-10 and 10-20 cm soil layers. The results showed that the average
      contents of MBC in 0-20 cm soil layer were 124.84, 325.29, 349.79 and 319.02 mg .
      kg-1 in the leaf litter removal treatment, Betula platyphlla treatment, Populus
      davidiana treatment and Quercus mongolica treatment, and the corresponding
      average rates of MR were 0.66, 1.12, 1.16 and 1.10 ug . g-1 . h-1, respectively.
      Meanwhile, in 0-20 cm soil layer, the average contents of MBC in the treatments
      with single leaf litter, mixed litter of two plant species and mixed litter of
      three plant species were 331. 37, 418. 52 and 529. 34 mg . kg-1, and the
      corresponding average rates of MR were 1.13, 1.30 and 1.46 ug . g-1 . h-1,
      respectively. In contrast to the MBC and MR, qCO2 in soil showed a reverse
      pattern. Our study suggested that characteristics of microbial carbolic
      metabolism were influenced by litter quality. Namely, the treatment with high
      litter quality had higher MBC, MR and utilization efficiency of soil carbon,
      compared with the treatment with low litter quality. Moreover, mixture of
      different species of leaf litter improved soil microbial activities, increased
      utilization efficiency on soil carbon and promoted diversity of microbial
      metabolic pathways, which could then contribute to maintaining and enhancing soil
      quality of forestland.

PMID- 26211052
TI  - [Litter decomposition and soil faunal diversity of two understory plant debris in
      the alpine timberline ecotone of western Sichuan in a snow cover season].
AB  - In order to understand the relationship between litter decomposition and soil
      fauna diversity during snow cover season, litterbags with plant debris of
      Actinothuidium hookeri, Cystopteris montana, two representative understory plants
      in the alpine timberline ecotone, and their mixed litter were incubated in the
      dark coniferous forest, timberline and alpine meadow, respectively. After a snow
      cover season, the mass loss and soil fauna in litterbags were investigated. After
      decomposition with a snow cover season, alpine meadow showed the highest mass
      loss of plant debris in comparison with coniferous forest and timberline, and the
      mass loss of A. hookeri was more significant. The mixture of two plants debris
      accelerated the mass loss, especially in the timberline. A total of 968 soil
      invertebrates, which belonged to 5 classes, 10 orders and 35 families, were
      captured in litterbags. Acarina and Collembola were the dominant groups in plant
      debris. The numbers of individuals and groups of soil faunal communities in
      litter of timberline were higher than those of alpine meadow and dark coniferous
      forest. Canonical correspondence analysis (CCA) indicated that the groups of soil
      animals were related closely with the average temperature, and endemic species
      such as Isoptera and Geophilomorpha were observed only in coniferous forest,
      while Hemiptera and Psocoptera only in.the alpine meadow. The diversity of soil
      faunal community was more affected by plant debris varieties in the timberline
      than in the coniferous forest and alpine meadow. Multiple regression analysis
      indicated that the average temperature and snow depth explained 30.8% of the
      variation of litter mass loss rate, soil animals explained 8.3%, and altogether
      explained 34.1%. Snow was one of the most critical factors impacting the
      decomposition of A. hookeri and C. montana debris in the alpine timberline
      ecotone.

PMID- 26211053
TI  - [Correlation between chemical constituents and ecological factors of Astragalus
      membranaceus var. mongholicus].
AB  - Principal component analysis (PCA) and correlation analysis (CA) were applied to
      analyze the correlation of the main chemical components in Astragalus
      membranaceus var. mongholicus and ecological factors. The results showed that the
      contents of astragaloside, campanulin, ononin, kaempferol and astragalus
      polysaccharides (APS) of A. membranaceus var. mongholicus produced. in Shanxi
      were significantly higher than in Inner Mongolia and Gansu. The main climatic
      factors for affecting the contents of chemical ingredients in A. membranaceus
      var. mongholicus were annual average relative humidity, sunshine hours and
      average July temperature. Calcium was the main factor in the soil affecting the
      chemical ingredient contents, and calcium was negatively correlated with the
      contents of calycosin glycosides, kaempferol, ononin, quercetin and APS in A.
      membranaceus var. mongholicus within a certain range.

PMID- 26211054
TI  - [Effects of nitrogen and water addition on soil bacterial diversity and community
      structure in temperate grasslands in northern China].
AB  - In this study, we measured the responses of soil bacterial diversity and
      community structure to nitrogen (N) and water addition in the typical temperate
      grassland in northern China. Results showed that N addition significantly reduced
      microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) under regular
      precipitation treatment. Similar declined trends of MBC and MBN caused by N
      addition were also found under increased precipitation condition. Nevertheless,
      water addition alleviated the inhibition by N addition. N addition exerted no
      significant effects. on bacterial alpha-diversity indices, including richness,
      Shannon diversity and evenness index under regular precipitation condition.
      Precipitation increment tended to increase bacterial alpha-diversity, and the
      diversity indices of each N gradient under regular precipitation were much lower
      than that of the corresponding N addition rate under increased precipitation.
      Correlation analysis showed that soil moisture, nitrate (NO3(-)-N) and ammonium
      (NH4+-N) were significantly negatively correlated with bacterial evenness index,
      and MBC and MBN had a significant positive correlation with bacterial richness
      and evenness. Non-metric multidimensional scaling (NMDS) ordination illustrated
      that the bacterial communities were significantly separated by N addition rates,
      under both water ambient and water addition treatments. Redundancy analysis (RDA)
      revealed that soil MBC, MBN, pH and NH4+-N were the key environmental factors for
      shaping bacterial communities.

PMID- 26211055
TI  - [Effects of compound fertilizer of (NH2)2CO and KH2PO4 on the chestnut
      photosynthesis characteristics, growth and fruiting].
AB  - Compound fertilizer can improve the fertilizer use efficiency and tree nutrition
      status to ensure balanced fertilization. Taking 7 year-old chestnut trees as test
      material, with (NH2)2CO and KH2PO4 being mixed at the different ratios, the
      effects of different compound fertilizers on the photosynthesis characteristics
      as well as the growth and fruiting of chestnut were studied quantitatively by
      trunk injection method. Results showed that compound fertilizer of (NH2)2CO and
      KH2PO4 induced positive synergistic effects to enhance photosynthetic capacity,
      yield and quality of chestnut obviously. The content of chlorophyll was decreased
      by (NH2)2CO and increased by KH2PO4, but increased obviously by the compound
      fertilizer. The contents of N, P, K of leaf and branch rose under the four
      compounded fertilization treatments, among which 0.3%(NH2)2CO+0.3%KH2PO4 was the
      best. All fertilizer treatments could advance the photosynthetic parameters,
      while the compound fertilizer performed better. 0.3% (NH2)2CO + 0.3% KH2PO4
      treatment significantly increased the photosynthetic rate, the maximum net
      photosynthesis, apparent quantum yield, carboxylation efficiency, instantaneous
      water use efficiency and nitrogen use efficiency. Compound fertilizer could
      promote the growth of branch in diameter and length synchronously, and increase
      the number of mixed buds, while (NH2)2CO only promoted the growth of branch in
      length, and did little in the number of mixed buds. The compound fertilizer did
      better in advancing nuts yield and quality than single fertilization of N or P.
      The nuts yield, mass and total sugar were increased by 68.2%, 25.5% and 14.9%
      respectively under 0.3% (NH2)2CO+0.3%KH2PO4 treatment compared with the control.

PMID- 26211056
TI  - [Effect of fertilization depth on 15N-urea absorption, utilization and loss in
      dwarf apple trees].
AB  - Five-year-old 'Fuji'3/M26/M. hupehensis Rehd. seedlings were treated by 15N
      tracer to study the effects of fertilization depth (0, 20 and 40 cm) on 15N-urea
      absorption, distribution, utilization and loss in soil. The results showed that
      the plant leaf area, chlorophyll content and total N of apple leaves in 20 cm
      treatment were obviously higher than 0 cm and 40 cm treatments. The 15N derived
      from fertilizer (Ndff) in different organs of apple plant under different depths
      were significantly different, and the Ndff was the highest in roots at the full
      bloom stage, and then in perennial branches. During the shoot rapid-growing and
      flower bud differentiation stage, the Ndff of new organs higher than that of the
      storage organs, and the Ndff of different organs were high level at fruit rapid
      expanding stage, and the Ndff of fruit was the highest. The distribution ratio of
      15N at fruit maturity stage was significantly different under fertilization
      depths, and that of the vegetative and repro- ductive organs of 20 cm treatment
      were obviously higher than 0 cm and 40 cm treatments, but that of the storage
      organs of 20 cm treatment was lower than 0 cm and 40 cm treatments. At fruit
      maturity stage, 15N utilization rate of apple plant of 20 cm treatment was 24.0%,
      which was obviously higher than 0 cm (14.1%) and 40 cm (7.6%) treatments, and 15N
      loss rate was 54.0%, which was obviously lower than 0 cm (67.8%) and 40 cm
      (63.5%) treatments. With the increase of fertilization depths, the N residue in
      soil increased sharply.

PMID- 26211057
TI  - [Monitoring of seasonal variation of vegetation cover and evaluation of
      biological-control factor in orchards of China].
AB  - Biological-control factor (B) can quantitatively reflect the effect of vegetation
      on soil erosion. Vertical photography method was used to monitor the seasonal
      changes of orchard coverage in 18 small watersheds, covering all five water
      erosion zones in China. The canopy coverage and ground green coverage were then
      calculated, and the B values were estimated. The result indicated that the
      orchard canopy coverage varied with season and distributed with a bell shape. The
      trend of ground green coverage and total coverage changed with season and was
      affected by the land management. For the orchard where the land surface was not
      treated and the weeds could grow freely, the distribution of the green coverage
      season change for all five soil erosion zones had a bell shape. The total
      coverage in the Northwest Loess Plateau area changed with season with a bell
      shape as well. The total coverage in the other four areas did not vary with the
      season and almost kept constant. For the orchard where land surface was cleaned
      up from time to time, the green coverage and total coverage in all five water
      erosion areas irregularly varied with season. The average B value of orchards in
      Northeast black soil area was the minimum with a value of 0.0006, while that in
      the Northwest Loess Plateau area was the maximum (0.1212). The average orchard B
      values in the Northern rocky earthy area, the Southern red soil area and the
      Southwest rocky earthy area were not significantly different and were 0.0548,
      0.0627 and 0.0639, respectively.

PMID- 26211058
TI  - [Spatial distribution of soil moisture and salinity and their influence factors
      in the farmland of Manas River catchment, Northwest China].
AB  - Applying methods of statistics and geo-statistics, Manas River catchment was
      selected as the research area to study the spatial distribution of soil moisture
      and salinity in the soil profile as. well as their influence factors. The
      coupling relationship between soil moisture and salinity presented in the spatial
      distribution was explored as well. The result showed that the soil moisture was
      overall at a low level (varying from 14.2% to 20.9%), while the salinity was
      relatively high (about 6.00-9.15 g . kg-1). The soil profile distribution of
      water and salt contents both showed a trend of bottom accumulation. The variation
      of soil water moisture was moderate, while that of salt content was strong. Soil
      salinity and moisture of all layers showed strong spatial autocorrelation, which
      were mainly affected by structural factors. The horizontal distribution patterns
      of water and salt contents were irregular, and were constrained by factors like
      terrain and landforms, etc. Disturbed by human activities, the coupling relation
      of soil moisture and salinity became much more complex, but their spatial
      distribution variation was synchronized to some extent.

PMID- 26211059
TI  - [Land use pattern change in Ejin Delta of Northwest China during 1930-2010].
AB  - The land use and landscape pattern in the lower reaches of the arid inland river
      basin is meaningful to water resource allocation. Based on the land use data in
      1930, 1961, 1990, 2000, 2010, the purpose of this study was to quantitatively
      analyze the change of landscape pattern in the Ejin Delta in the lower reaches of
      the Heihe River Basin, a typical inland river basin in Northwest China. The
      results showed that the desert area accounted for 73.4% of the total research
      area in 2010, and the grassland 20.8%. During the past 80 years, the grassland,
      farmland and construction land increased. The transformation of land use types
      were characterized by switching to farmland and construction land. The
      fragmentation and. diversity of the landscape increased, while the dominance of
      the landscape decreased. The landscape pattern obviously lied on the water
      resource and had regional diversity. Land use changes tended to make the
      landscape well-distributed, diverse and fragmentized. At last, the driving
      factors and ecological environment effects of land use change were discussed. In
      a word, to ensure harmonious development between human and eco-hydrology,
      suggestions such as planning ecological resettlement, limiting farmland area,
      developing precision agriculture and increasing the proportion of ecological
      water use should be put forward.

PMID- 26211060
TI  - [Variation characteristics of agricultural heat resource and its effect on
      agriculture in Shanxi Province, China].
AB  - Based on the data of the daily mean air temperature and the minimum soil surface
      temperature of 70 meteorological stations in Shanxi Province from 1970 to 2012,
      the heat indices of agricultu-ral resources including accumulated temperatures
      above 0  degrees C and 10  degrees C , the average temperature in July and the
      annual frost-free duration were calculated. Their variation trends and mutation
      were analyzed by using linear regression and accumulated anomaly methods. The
      effect of agricultural heat resource on crop producing area was analyzed. The
      results showed that the accumulated temperatures for above 0  degrees C and 10 
      degrees C had increased significantly at a rate of about 64.8 and 57.9  degrees C
      . d . (10 a) -1, respectively (P<0.001). The average temperature in July and the
      annual frost-free duration had significantly increased at a rate of about 0.3 
      degrees C. (10 a)-1 and 5.9 d . (10 a)-1, respectively. The increasing ranges of
      heat resource indices had different spatial distribution patterns in Shanxi
      Province. The accumulated temperatures were greater in the west than that in the
      east. The average temperature in July was greater in middle and north than that
      in the south. The annual frost-free duration was greater in the middle than that
      in the south and north. The accumulated temperatures above 0  degrees C and 10 
      degrees C showed a clear mutation in 1996, so were the average temperature in
      July in 1993 and the annual frost-free duration in 1997. Compared to the time
      before mutation, the accumulated temperatures above 0  degrees C and 10  degrees
      C increased by 219.4  degrees C . d and 196.7  degrees C . d, respectively, the
      average temperature in July by 0.8  degrees C and the annual frost-free duration
      by 15 d. As a result, hot crop cultivable area and warm crop cultivable area were
      expanded northward, while the mild crop cultivable area, cool crop cultivable
      area, cold crop cultivable area and alpine plants area were shrunk. The maximum
      expansion was of the warm crop cultivable area (by 175.7%). The maximum shrinkage
      was of the cold area (by 87.9 %). The cultivable area of cotton was expanded by
      1.7 x 10(6)hm2(53.5%), and that of potato was shrunk by 8.9 x 10(6) hm2(30.5%).

PMID- 26211061
TI  - [China's rice field greenhouse gas emission under climate change based on DNDC
      model simulation].
AB  - In contrast to a large body of literature assessing the impact of agriculture
      greenhouse gas (GHG) emissions on climate change, there is a lack of research
      examining the impact of climate change on agricultural GHG emissions. This study
      employed the DNDC v9.5, a state-of-art biogeochemical model, to simulate
      greenhouse gas emissions in China' s rice-growing fields during 1971-2010. The
      results showed that owing to temperature rising (on average 0.49  degrees C
      higher in the second 20 years than in the first 20 year) and precipitation
      increase (11 mm more in the second 20 years than in the first 20 years) during
      the rice growing season, CH4 and N2O emissions in paddy field increased by 0.25
      kg C . hm-2 and 0.25 kg N . hm-2, respectively. The rising temperature
      accelerated CH4 emission and N2O emission increased with precipitation. These
      results indicated that climate change exerted impact on the mechanism of GHG
      emissions in paddy field.

PMID- 26211062
TI  - [Simulated responses of winter wheat yield and soil moisture to different
      conservation tiliage practices in Weibei Highlands, Northwest China].
AB  - Based on the verified precision results by simulation, the WinEPIC (EPIC,
      environmental/policy integrated climate model) was employed to quantitatively
      simulate effects of three conservation tillage practices adopted during the
      period of summer fallow, i.e. sub-soiling, no-tillage and conventional tillage,
      on wheat yield and soil moisture in Weibei Highlands during 1980-2009. The
      results showed that during the study period, the yield and annual water
      consumption of winter wheat under the different tillage practices tended to
      decrease with fluctuation in the growing period. The yield and water use
      efficiency of winter wheat under sub-soiling were the highest, averaging 3.33 t .
      hm-2 and 8.50 kg . hm-2 . mm-1 over the thirty years, respectively, and that of
      no tillage was the lowest. The annual water consumption of winter wheat was
      .slightly higher under sub-soiling than under no tillage and conventional
      tillage. In 0-3 m soil layer, the available soil water content tended to decline
      in a strongly and seasonally fluctuating manner. No tillage performed best in
      soil moisture conservation, with the average available soil water content being
      89.5 mm, and that of conventional tillage was the lowest. The soil water moisture
      fluctuated with the seasonal rainfalls in 0-1 m soil layer and kept stable in 1-3
      m with no great difference among the tillage practices. Under long-term
      continuous cropping, sub-soiling showed the best effects on the yield of winter
      wheat and the most comprehensive effect on soil moisture, and was the best
      practice of conservation tillage for wheat lands on Weibei Highlands.

PMID- 26211063
TI  - [Selenium uptake and transport of rice under different Se-enriched natural
      soils].
AB  - In this study, a pot experiment was conducted with "Wandao 205" as test materials
      to investigate Se uptake and translocation in rice under different Se
      concentrations (0.5, 1.0, and 1.5 mg . kg-1). Results showed that there was no
      significant change in rice yield when Se concentration in soil was lower than 1.5
      mg . kg-1. Significant linear correlations existed between Se concentration in
      soil and different rice plant tissues. Se concentration in rice plant followed
      the order of root > straw > grain. Se concentration in different rice grain
      fractions followed the order of bran > polished rice > hull. The root absorption
      index of Se was more than 1.86, suggest that the rice could absorpt Se from soil
      effectively. However, the transport and accumulation of Se in seeds from Se
      enriched soil was relatively constant. The Se transport index in seeds was
      between 0.53 and 0.59. Soil Se concentration within the range of 0.5 to 1.0 mg .
      kg-1 could produce Se-enriched rice, which might be enough for human requirement
      of 60-80 ug . d-1 Se. However, polished rice at high-Se treatment (1.5 mg . kg-1)
      exceeded the maximum standard limit of Se (0.3 mg . kg-1) for cereals in China.
      These results suggested that we could produce Se-enriched rice under soil Se
      concentration in the range of 0.5 to 1.0 mg . kg-1 without spraying Se
      fertilizer, thus reducing the cost and avoiding soil and water pollution caused
      by exogenous Se.

PMID- 26211064
TI  - [Effects of reduced nitrogen application and soybean intercropping on nitrogen
      balance of sugarcane field].
AB  - A four-year (2010-2013) field experiment was carried out to explore the effects
      of three planting patterns (sugarcane, soybean monoculture and sugarcane-soybean
      1:2 intercropping) with two nitrogen input levels (300 and 525 kg . hm-2) on
      soybean nitrogen fixation, sugarcane and soybean nitrogen accumulation, and
      ammonia volatilization and nitrogen leaching in sugarcane field. The results
      showed that the soybean nitrogen fixation efficiency (NFE) of sugarcane-soybean
      inter-cropping was lower than that of soybean monoculture. There was no
      significant difference in NFE among the treatments with the two nitrogen
      application rates. The nitrogen application rate and inter-cropping did not
      remarkably affect nitrogen accumulation of sugarcane and soybean. The ammonia
      volatilization of the reduced nitrogen input treatment was significantly lower
      than that of the conventional nitrogen input treatment. Furthermore, there was no
      significant difference in nitrogen leaching at different nitrogen input levels
      and among different planting patterns. The sugarcane field nitrogen balance
      analysis indicated that the nitrogen application rate dominated the nitrogen
      budget of sugarcane field. During the four-year experiment, all treatments leaved
      a nitrogen surplus (from 73.10 to 400.03 kg . hm-2) , except a nitrogen deficit
      of 66.22 kg . hm-2 in 2011 in the treatment of sugarcane monoculture with the
      reduced nitrogen application. The excessive nitrogen surplus might increase the
      risk of nitrogen pollution in the field. In conclusion, sugarcane-soybean
      intercropping with reduced nitrogen application is feasible to practice in
      consideration of enriching the soil fertility, reducing nitrogen pollution and
      saving production cost in sugarcane field.

PMID- 26211065
TI  - [Effect of different organic fertilizers on bioavailability of soil Cd and Zn].
AB  - The active effect of soil Cd and Zn and their interaction was studied in typical
      paddy field in south China by monitoring the contents of Cd and Zn in soil and
      rice in rice fields applied with pig manure, chicken manure or rice straw for 4
      years continuously. The results showed that applying pig manure, chicken manure
      or rice straw had no significant impact on the soil total Cd content, soil
      available Cd content and soil Cd activity, but tended to increase the soil total
      Cd content and increased the soil total Zn content, soil available Zn content and
      Zn activity significantly. Applications of pig manure, chicken manure and rice
      straw all reduced the Cd content of brown rice, in order of pig manure > chicken
      manure > rice straw. The Cd contents of brown rice, stem and leaf in the
      treatment applied with pig manure were lower than in the control by 37.5%, 44.0%
      and 36.4%, respectively; the Cd contents of brown rice, stem and leaf in the
      treatment applied with chicken manure were lower than in the control by 22.5%,
      33.8%, and 22.7%, respectively; the Cd content of brown rice in the treatment
      applied with rice straw was lower than in the control by 7.5% but its contents in
      stem and leaf increased by 8.2% and 22.7% , respectively. The reduction in the
      brown rice Cd content was mainly due to the reduction of Cd enrichment from soil
      to brown rice after application of pig or chicken manure, but mainly due to the
      reduction of Cd transportation from stem to brown rice after straw application.
      Applications of pig manure, chicken manure and rice straw increased Zn contents
      in rice stem by 53.4%, 53.4% and 13.9%, respectively, but all had no significant
      effect on brown rice and leaf' s Zn contents. Zn and Cd had the significant
      antagonistic effects in the soil and rice stem. The increase of Zn content in
      soil and rice stem inhibited the adsorption and accumulation of Cd in the brown
      rice, stem and leaf significantly, and with the increase of the proportion of
      Zn/Cd, the competitive absorption between Cd and Zn by rice was the main control
      factor affecting the Cd absorption by rice than their competitive adsorption by
      soil.

PMID- 26211066
TI  - [Effects of different long-term fertilization on the activities of enzymes
      related to carbon, nitrogen, and phosphorus cycles in a red soil].
AB  - Using a microplate fluorimetric assay method, five fertilization treatments, i.e.
      no-fertilizer control (CK) , sole application of nitrogen (N), balanced
      application of nitrogen, phosphorus, and potassium fertilizer (NPK), application
      of pig manure (M), and combination of pig manure with balanced chemical
      fertilizer (MNPK) were selected to investigate the effects of different long-term
      fertilization regimes on the activity of five enzymes (beta-1, 4-glucosidase,
      betaG; cellobiohydrolase, CBH; beta-1, 4-xylosidase, betaX; beta-1, 4-N
      acetylglucosaminidase, NAG; acid phosphatase, AP) in a red soil sampled from
      Qiyang, Hunnan Province. The results showed that compared with CK treatment, N
      treatment had no impact on betaG, betaX, CBH, and NAG activities but reduced AP
      activity, while NPK, M and MNPK treatments increased the activities of all the
      five enzymes. Correlation analysis indicated that all the five enzyme activities
      were positively correlated with the content of nitrate (r=0.465-0.733) , the
      content of available phosphorus (r=0.612-0.947) , soil respiration (r=0.781
      0.949) and crop yield (r=0.735-0.960), while betaG, CBH and AP were positively
      correlated with pH (r= 0.707-0.809), only AP was significantly correlated with
      dissolvable organic carbon (r = -0.480). These results suggested that the
      activities of the measured enzymes could be used as indicators of red soil
      fertility under different fertilization regimes, but the five enzymes tested
      provided limited information on the degree of acidification induced by
      application of mineral nitrogen.

PMID- 26211067
TI  - [Impact of temperature increment before the over-wintering period on growth and
      development and grain yield of winter wheat].
AB  - The effect of temperature increment before the over-wintering period on winter
      wheat development and grain yield was evaluated in an artificial climate chamber
      (TPG 1260, Australia) from 2010 to 2011. Winter wheat cultivar 'Zhengmai 7698'
      was used in this study. Three temperature increment treatments were involved in
      this study, i.e., temperature increment last 40, 50 and 60 days, respectively,
      before the over-wintering period. Control was not treated by temperature
      increment. The results showed that temperature increment before the over
      wintering period had no significant effect on earlier phase spike
      differentiation. But an apparent effect on later phase spike differentiation was
      observed. High temperature effect on spike differentiation disappeared when the
      difference of effective accumulated temperature between the temperature increment
      treatment and the control was lower than 25  degrees C. However, the foliar age
      at the jointing stage was enhanced more than 0.8, heading and physiological
      ripening were advanced 1 day each, when the effective accumulated temperature
      before the over-wintering period increased 60  degrees C. Higher effective
      accumulated temperature before the over-wintering period accelerated winter wheat
      growth and development, which resulted in a short spike differentiation period.
      Winter wheat was easy to suffer freeze damage, which lead to floret abortion and
      spikelet death in spring under this situation. Meanwhile, higher effective
      accumulated temperature before the over-wintering period also reduced,
      photosynthetic capacity of flag leaf, shortened the grain filling period, and led
      to wheat grain yield reduction.

PMID- 26211068
TI  - [Effects of exogenous 24-epibrassinolde on leaf morphology and photosynthetic
      characteristics of tomato seedlings under low light stress].
AB  - This study investigated the effects of exogenous 24-epibrassinolide (EBR) on the
      leaf morphology and photosynthetic characteristics of tomato seedlings (cv.
      Jiersi) cultured hydroponically under low light stress. The results showed that
      low light stress induced adaptive changes in the leaf morphology of tomato
      seedling. Low light stress significantly increased the leaf area, specific leaf
      area, angle between stem and leaf, vertical angle and cable bent, but
      significantly decreased the dry mass of leaf. Low light stress also significantly
      decreased the maximum net photosynthetic rate,. apparent quantum yield, dark
      respiration rate, carboxylation efficiency and Rubisco large subunit content. The
      light compensation point and carbon dioxide compensation point were dramatically
      enhanced under low light stress. However, foliar spraying EBR significantly
      increased the leaf area, leaf dry mass, angle between stem and leaf, vertical
      angle by 14.1%, 57.1%, 12.3% and 7.7% under low light stress, respectively. EBR
      significantly decreased the specific leaf area and cable bent by 30.5% and 10.6%
      in low light stressed plants. In addition, EBR significantly enhanced the
      apparent quantum yield, dark respiration rate and carboxylation efficiency by
      20.4%, 17.9% and 9.3%, respectively, but significantly reduced the light
      compensation point and carbon dioxide compensation point by 21.9% and 4.3% under
      low light stress. Moreover, EBR also significantly increased the Rubisco large
      subunit content in low light stressed leaves. These results suggested that
      application of exogenous EBR could effectively alleviate the inhibition of
      photosynthesis induced by low light stress via improving the apparent quantum
      yield, dark respiration rate, carboxylation efficiency and Rubisco content, and
      maintaining the stability of leaf morphology, thus low light tolerance of tomato
      seedlings.

PMID- 26211069
TI  - [Effects of brief exposure to high temperature on Neoseiulus californicus].
AB  - To determine the influence of high temperature shock on the survival
      characteristics and population development of N. californicus, the hatching rate,
      survival rate and developmental duration were investigated after the eggs, larvae
      and adults of N. californicus were exposed to high temperatures (35, 38, 42, 45 
      degrees C) for 1-8 h. The results showed that with higher temperature and longer
      time, the survival rate of eggs and larvae would be lower, and their
      developmental duration declined firstly and then increased. The hatching rate of
      eggs treated at 42  degrees C for 8 h was significantly lower than that at 35 
      degrees C for 8 h. The developmental duration of egg (4.1 d) was shortest when
      treated at 38  degrees C for 8 h. The egg couldn't hatch when treated at 45 
      degrees C for 2 h. The survival rate of larvae which was treated at 45  degrees C
      for 4 h was significantly lower than. that at 35  degrees C for 4 h, and the
      larvae wouldn' t survive when treated at 45  degrees C for 8 h. The spawning
      period and total eggs of female adults increased firstly and then decreased. The
      egg-laying amount of a female N. californicus was 38.9, 36.7 and 14.5 at 35, 38
      and 45  degrees C, respectively. High temperature exposure had significant
      effects on the egg hatching rate, survival rate and development duration of N.
      californicus, but had little effect on the pre-oviposition and survival rate of
      the adults.

PMID- 26211070
TI  - [Identification of chemicals in root exudates of potato and their effects on
      Rhizoctonia solani].
AB  - This study was conducted to identify chemicals in root exudates and their effect
      on Rhizoctonia solani in potato cropping systems. Root exudates were collected
      from the fields with 5 years of continuous potato cropping in comparison with
      rotational cropping of potato and other crops, using in-house made root boxes at
      the seedling and squaring stages. Chemicals in the root exudates were identified
      using the GC-MS method. The results showed that glucide concentration was the
      highest in the root exudates, followed by organic acids. Compared with the
      rotational cropping, the continuous cropping significantly decreased the glucide
      content and increased the content of organic acids in the root exudates. The
      contents of almitic acid in root exudates under continuous cropping was 0.94% at
      seedling stage and 1.4% at squaring stage, the dibutyl phthalate was 0.15%,
      whereas under rotational cropping, those values were decreased to 0.15%, 0.2%,
      and being negligible, respectively. The root exudates promoted the growth of R.
      solani, especially under continuous potato cropping. The simulation test showed
      that the palmitic acid and dibutyl phthalate in root exudates could promote the
      growth of R. solani.

PMID- 26211071
TI  - [Temporal characteristics of ecological risk assessment indicators in coal-mining
      city with the application of LVQ method].
AB  - Because the ability of selected indicators in assessing ecological risk at
      different temporal scales is not the same, it is necessary to clear the definite
      comparability of such indicators at temporal scale to explore a new method for
      dynamic assessing the ecological risk. In this case, five mining cities in
      Liaoning Province were selected as the study area, with the application of
      learning vector quantization (LVQ) neural network, the significance of the
      indicators for the ecological risk assessment was quantitatively analyzed to
      clarify their characteristics at temporal scale. The expression with two
      dimension (long-term and short-term) of temporal scale was put forward as a new
      method to assess the ecological risk for mining cities. The results showed that
      the amount of industrial SO2 removed per output value, the amount of industrial
      dust removed per output value, coverage rate of urban green space, precipitation,
      coordination degree among subsystems, percentage of mining practitioners, and
      current year investment on pollution abatement projects were effective at long
      term temporal scale, while the other indicators acted at short-term temporal
      scale. With the combination of long-term and short-term temporal scales, the
      dynamic assessment of ecological risk for mining cities could be expressed on two
      dimension of temporal scale. It was found that Fuxin City got the highest
      ecological risk in current status, with the risk increasing most in Fushun City
      at the short-term temporal scale as well as in Chaoyang City at the long-term
      temporal scale. The method adopted in this study might act as a significant
      guidance in dynamic controlling and integrative management of ecological risk for
      mining cities.

PMID- 26211072
TI  - [Ecology-economy harmonious development based on the ecological services value
      change in Yanqi Basin, Northwest China].
AB  - In this paper, we used land use/cover ecosystem service value estimation model
      and ecological economic coordination degree model to analyze the changes of the
      ecosystem service value by the land use/cover changes during 1985, 1990, 1996,
      2000, 2005 and 2011 in Yanqi Basin, Xin-jiang. Then we evaluated the ecology
      economy harmony and the regional differences. The results showed that during 1985
      2011, there was an increasing trend in the areas of waters, wetland, sand,
      cultivated land and construction land in Yanqi Basin. In contrast, that of the
      saline-alkali land, grassland and woodland areas exhibited a decreasing trend.
      The ecosystem service value in Yanqi Basin during this period presented an
      increasing trend, among which the waters and cultivated land contributed most to
      the total value of ecosystem services, while the grassland and the woodland had
      obviously declined contribution to the total value of ecosystem services. The
      research showed that the development of ecological economy in the study area was
      at a low conflict and low coordination level. So, taking reasonable and effective
      use of the regional waters and soil resources is the key element to maintain the
      ecosystem service function and sustainable and harmonious development of economy
      in Yanqi Basin.

PMID- 26211073
TI  - [Spectral reflectance characteristics and modeling of typical Takyr Solonetzs
      water content].
AB  - Based on the analysis of the spectral reflectance of the typical Takyr Solonetzs
      soil in Ningxia, the relationship of soil water content and spectral reflectance
      was determined, and a quantitative model for the prediction of soil water content
      was constructed. The results showed that soil spectral reflectance decreased with
      the increasing soil water content when it was below the water holding capacity
      but increased with the increasing soil water content when it was higher than the
      water holding capacity. Soil water content presented significantly negative
      correlation with original reflectance (r), smooth reflectance (R), logarithm of
      reflectance (IgR), and positive correlation with the reciprocal of R and
      logarithm of reciprocal [lg (1/R)]. The correlation coefficient of soil water
      content and R in the whole wavelength was 0.0013, 0.0397 higher than r and lgR,
      respectively. Average correlation coefficient of soil water content with 1/R and
      [lg (1/R)] at the wavelength of 950-1000 nm was 0.2350 higher than that of 400
      950 nm. The relationships of soil water content with the first derivate
      differential (R') , the first derivate differential of logarithm (lgR)' and the
      first derivate differential of logarithm of reciprocal [lg(1/R)]' were unstable.
      Base on the coefficients of r, lg(1/R), R' and (lgR)', different regression
      models were established to predict soil water content, and the coefficients of
      determination were 0.7610, 0.8184, 0.8524 and 0.8255, respectively. The
      determination coefficient for power function model of R'. reached 0.9447, while
      the fitting degree between the predicted value based on this model and on-site
      measured value was 0.8279. The model of R' had the highest fitted accuracy, while
      that of r had the lowest one. The results could provide a scientific basis for
      soil water content prediction and field irrigation in the Takyr Solonetzs region.

PMID- 26211074
TI  - [Application of simulated annealing method and neural network on optimizing soil
      sampling schemes based on road distribution].
AB  - Taking the soil organic matter in eastern Zhongxiang County, Hubei Province, as a
      research object, thirteen sample sets from different regions were arranged
      surrounding the road network, the spatial configuration of which was optimized by
      the simulated annealing approach. The topographic factors of these thirteen
      sample sets, including slope, plane curvature, profile curvature, topographic
      wetness index, stream power index and sediment transport index, were extracted by
      the terrain analysis. Based on the results of optimization, a multiple linear
      regression model with topographic factors as independent variables was built. At
      the same time, a multilayer perception model on the basis of neural network
      approach was implemented. The comparison between these two models was carried out
      then. The results revealed that the proposed approach was practicable in
      optimizing soil sampling scheme. The optimal configuration was capable of gaining
      soil-landscape knowledge exactly, and the accuracy of optimal configuration was
      better than that of original samples. This study designed a sampling
      configuration to study the soil attribute distribution by referring to the
      spatial layout of road network, historical samples, and digital elevation data,
      which provided an effective means as well as a theoretical basis for determining
      the sampling configuration and displaying spatial distribution of soil organic
      matter with low cost and high efficiency.

PMID- 26211075
TI  - [Effect of climate change on the fisheries conununity pattern in the
      overwintering ground of open waters of northern East China Sea].
AB  - Data sets of 26 fisheries target species from the fishery-depen-dent and fishery
      independent surveys in the overwintering ground of open waters of northern East
      China Sea (OW-NECS), combined sea surface temperature (SST), were used to examine
      the links between diversity index, pattern of common variability and climate
      changes based on the principal component analysis (PCA) and generalized additive
      model (GAM). The results showed that the shift from a cold regime to a warm
      regime was detected in SST during the 1970s-2011 with step changes around 1982/
      1983. SST increased during the cold regime and the warm regime before 1998
      (warming trend period, 1972-1998), and decreased during the warm regime after
      1998 (cooling trend period, 1999-2011). Shannon diversity index was largely
      dependent on the filefish, which contributed up to 50% of the total production as
      a single species, with low diversity in the waters of the OW-NECS, during the
      late 1980s and early 1990s. Excluding the filefish, the diversity index linearly
      increased and decreased during 1972-1998 and 1999-2011, respectively. The
      variation pattern generally corresponds with the trend in water temperature,
      strongly suggesting the effect of the SST on the diversity. The first two
      components (PC1 and PC2) of PCA for target species, which accounted for 32.43% of
      the total variance, showed evident decadal variation patterns with a step change
      during 1992-1999 and inter-annual variability with short-period fluctuation,
      respectively. It seems that PC1 was associated with large scale climatic change,
      while PC2 was related to inter-annual oceanographic variability such as ENSO
      events. Linear fitting results showed winEOF1 had significant effect on PC1, and
      GAM analysis for PC1 showed that winter EOF1 (winEOF1) and summer EOF2 (sumEOF2)
      can explain 88.9% of the total variance. Nonlinear effect was also found between
      PC2 and win EOF1, indicating that the fish community structure, which had
      predominantly decadal/inter-annual variation patterns, was influenced by inter
      annual variations in oceanographic conditions.

PMID- 26211076
TI  - [Vertical distribution of main species captured by tuna longline fishery in the
      southeast Pacific Ocean].
AB  - Information of vertical distribution of longline-hook species is important for
      the development of effective measures to mitigate bycatch, and very helpful for
      better understanding of the oceanic ecosystem structure and implementation of
      ecosystem-based fisheries management. Based on depth data of longline hook and
      capture hook position of pelagic species, collected by on board scientific
      observer in the southeast Pacific Ocean from September 2013 to January 2014,
      shoaling rate of longline hook and vertical distribution of 14 pelagic species
      were analyzed. The results showed that the relative shoaling rate range of
      longline hook was 8.9% - 17.1%, and the average relative shoaling rate was 13.5%.
      The depth ranges of 14 capture species were different. The species with the
      deepest depth was Opah (Lampris guttatus), and the species with the shallowest
      depth was skipjack (Katsuwonus pelamis). Except for yellowfin tuna (Thunnus
      albacares) and striped marlin (Tetrapturus audax), the mean depth and depth
      distributions of bycatch species were significantly different from that of the
      targeted albacore tuna (Thunnus alalunga).

PMID- 26211077
TI  - [Advances in studies of absorption and utilization of amino acids by plants: A
      review].
AB  - Plant can directly take up the intact amino acids, thus bypass the microbial
      mineralization of organic nitrogen. As an excellent carbon and nitrogen source,
      there exists competition for amino acid absorption between plant roots.and soil
      microorganisms. And the total flux of amino acids in soil may be enormous due to
      the extensive sources and short half-life. Studies on amino acid nitrogen
      nutritional contribution for plant by the technique of nitrogen isotopic tracer,
      has become a research topic in recent years ,which will help us better understand
      the principle of soil fertility. This paper summarized the recent researches on
      amino acid morphological characteristics in soil and its metabolic mechanism and
      nitrogen nutritional contribution for plant in different ecosystems, and
      discussed the present status and development trend of the amino acid circulation
      mechanism in the plant-soil-microorganism ecosystem and its bioavailability for
      plant. Finally, the topics of environmental regulating mechanism of amino acid
      bioavailability, amino acid carbon-nitrogen metabolism, and how to improve the
      field organic nitrogen management were all the core issues to be resolved.

PMID- 26211079
TI  - [Effects of tillage methods on soil physicochemical properties and biological
      characteristics in farmland: A review].
AB  - Tillage methods affect soil heat, water, nutrients and soil biology in different
      ways. Reasonable soil management system can not only improve physical and
      chemical properties of the soil, but also change the ecological process of
      farmland soil. Conservation tillage can improve the quality of the soil to
      different degrees. For example, no-tillage system can effectively improve soil
      enzyme activity. No tillage and subsoiling tillage can provide abundant resources
      for soil microbe' s growth and reproduction. No tillage, minimum tillage and
      other conservation tillage methods exert little disturbance to soil animals, and
      in turn affect the quantity and diversity of the soil animals as well as their
      population structure. Effects of different tillage methods on soil physical and
      chemical properties as well as biological characteristics were reviewed in this
      article, with the soil physical and chemical indices, enzyme activities, soil
      microbe diversity and soil animals under different tillage patterns analyzed. The
      possibility of soil quality restoration with appropriate tillage methods and the
      future research direction were pointed out.

PMID- 26211078
TI  - [Impacts of climate change on food production in Gansu: A review].
AB  - The climate of Gansu turned to be overall warming-drying and partly warming
      wetting since 1986. In contrast to that of 1960, the average annual temperature
      had raised by 1.1 degrees C with the average annual precipitation decreased by 28
      mm correspondingly, which made the arid region expanded southward by 50 km in
      2010. Climate warming increased the growth period effective accumulated
      temperature of main food grain crops and lengthened the crop growth period. It
      changed crop maturity, crop disposition, cropping system and generally increased
      the cultivatable area and planting altitude above the sea level of major crops
      and expanded northward the multiple cropping system, which further resulted in
      expansion of autumn grain crop sown area, shrink of summer grain crop sown area,
      and replacement of strong winter early maturing varieties by weak winter middle
      late maturing varieties. It benefited the crop yield by increasing the use
      efficiency of photo-thermal resources. Warming-wetting climate increased the
      climate productivity of oasis crop while warming-drying weather decreased the
      climate productivity of rainfed crops, which were mostly determined by the
      precipitation regimes and water conditions. Any advanced technique that can
      increase precipitation use ratio and water use efficiency as well as improve and
      promote soil quality and fertility should be regarded as an effective
      countermeasure to increase food grain production under climate change in Gsansu.
      So, selecting and breeding new crop varieties with the characteristics of strong
      resistance, weak winter, middle-late mature and high water use efficiency,
      establishing new planting structure and cropping system that suitable to the
      precipitation and temperature features of changed climate, are the development
      direction of food grain production in Gansu to cope with the climate change.

PMID- 26211080
TI  - [Research progress on the application of IPAT model and its variants].
AB  - IPAT model and its variants could describe the quantitative relationships between
      human driving force and the environmental pressure, benefit fundamental
      understanding of the dynamics of coupled human and natural systems, and are
      regarded as effective tools in solving the environmental problems caused by the
      social and economic development. In this paper, the fundamental concepts of IPAT
      model and its variants were discussed including definitions, historical
      developments and the hot issues in their applications. The future research trends
      were put forward aiming to further expand the use of IPAT models in the
      sustainable development of environment and social decision-making.

PMID- 26211081
TI  - [Research progress on molecular ecology of Sciurus vulgaris].
AB  - Today, the main threats for Sciurus vulgaris are illegal hunting, deforestation,
      and subsequent population fragmentation, combined with interspecific competition
      from S. carolinensis in some regions of Europe, which has led to a sharp
      reduction in the number of population. S. vulgaris has been listed as Near
      Threatened IUCN Red List and included in key protected wild animals in Jilin
      Province, China. The molecular ecology of S. vulgaris is developing rapidly with
      the rapid development of molecular biology methods. In particular, the research
      of mtDNA fragments and the application squirrel study microsatellite loci has
      further promoted the molecular ecology of S. vulgaris. In this study, the
      molecular phylogeny, the genetic diversity and the molecular phylogeography
      involving the molecular ecology of S. vulgaris were reviewed. Four areas for the
      future development in molecular ecology of S. vulgaris were proposed: 1) to
      further explore the molecular phylogeny relationship between S. vulgaris and S.
      lis; 2) the comparative analysis of the genetic diversity of S. vulgaris for
      continuous populations, isolated populations and metapopulation; 3) the analysis
      of molecular phylogeography of S. vulgaris based on other markers of nuclear; 4)
      to explore whether there existed the quaternary glacial refuge in Asia.

PMID- 26211082
TI  - [Prevention of smoking due to electronic cigarettes and new cigarette products:
      it is getting more complicated!].

PMID- 26211083
TI  - [Electronic cigarette: what do we know in 2015?].
AB  - Electronic cigarettes are devices producing vapour containing propylene-glycol,
      flavourings and quickly delivered nicotine. 6.7% of the Swiss population, mainly
      smokers, experimented the electronic cigarette while 0.1% use it daily. Despite
      uncertainty due to the low level of evidence, electronic cigarettes might be
      effective for smoking cessation and reduction. The safety of electronic
      cigarettes is demonstrated at short-term but not at long-term; however its
      eventual toxicity is likely to be much lower than tobacco. Use of electronic
      cigarettes by non-smokers and youth who do not smoke is low and seems unlikely to
      lead them to tobacco use. Recommended public health measures include product
      regulation with quality control, ban in public places, prohibition of advertising
      and sales to minors.

PMID- 26211084
TI  - [Smoking cessation: update 2015].
AB  - Smoking remains a major public health problem in Switzerland and is responsible
      for about 9000 deaths annually. In 2013, a quarter of the Swiss population (15
      and over) were smokers and more than half of them wanted to quit smoking. This
      article provides an update of Swiss clinical practice guidelines published in
      2011 and covers several new features, including views regarding smoking
      reduction, gradual quitting, use of nicotine replacement therapy for a short
      period prior to quitting, nicotine mouth spray marketing and the reimbursement of
      varenicline and bupropion treatments (under certain conditions) by basic health
      insurance. An algorithm summarizes the different stages of management of patients
      who smoke.

PMID- 26211085
TI  - [Smoking and digestive tract: a complex relationship. Part 1: Inflammatory bowel
      disease and cigarette smoking].
AB  - Little is known about the effects of smoking on inflammatory bowel diseases
      (IBD). However the co-occurrence of smoking and IBD often happens in ambulatory
      care. Smokers have a doubled risk of developing a Crohn's disease with a more
      active disease course. After quitting, a decrease in risk can be observed after
      only one year. An inverse relationship is found between smoking and ulcerative
      colitis. Smoking seems protective for the development of the disease and its
      course is less active among smokers. Smoking cessation transitorily increases the
      risk of developing ulcerative colitis. Nevertheless, continuing smoking cannot be
      justified among those patients given the risks of long-term extra-digestive
      effects. It is thus important to counsel all smokers with an IBD to quit smoking.

PMID- 26211086
TI  - [Advertising and promotion of tobacco products and electronic cigarettes].
AB  - Switzerland is one of the least restrictive countries in Europe in terms of
      tobacco advertising. A study conducted between 2013 and 2014 documented the
      presence of tobacco advertising, promotion and sponsorship in western
      Switzerland. The first part of this article presents the results of the
      observations realized in points of sale, in private events sponsored by the
      tobacco industry and during daily itineraries of young people. The results show
      that tobacco advertising, promotion and sponsorship are omnipresent and mainly
      target young people. The second part of the article analyses the presence of
      electronic cigarette advertising and promotion, observed in points of sale and on
      online stores.

PMID- 26211087
TI  - [New tobacco vaporizers: how to react?].
AB  - Cigarette combustion, rather than either tobacco or nicotine, is the cause of a
      public health disaster. Fortunately, several new technologies that vaporize
      nicotine or tobacco may make cigarettes obsolete. Some of these new technologies
      are developed and owned by the tobacco industry, which invests massively for the
      research and development of these products. Because of its past scientific
      misconduct, the tobacco industry is ostracized. In the context of a fierce
      ideological debate on these new products, it is crucial that regulators and the
      public are provided with evidence-based guidance. Should the scientific
      production in this field be done with or without the tobacco industry? This
      thorny issue is discussed in this comment.

PMID- 26211088
TI  - [Gender and disparities: the example of tobacco smoking].
AB  - Smoking prevalence is globally five times higher among men compared to women but
      this gap tends to decrease. Regarding health consequences of smoking, women tend
      to be more vulnerable than men. They are namely more at risk to present certain
      lung cancers and die of cardiovascular disease. While men are less prone to seek
      help for smoking cessation, women are less successful in their quit attempts and
      smoking cessation treatments are less effective among them. Interventions for
      smoking cessation and preventive measures tailored to gender specificities have
      the potential to improve management of smokers and decrease gender disparities in
      healthcare.

PMID- 26211089
TI  - [Smoking and digestive tract: a complex relationship. Part 2: Intestinal
      microblota and cigarette smoking].
AB  - The digestive tract is colonized from birth by a bacterial population called the
      microbiota which influences the development of the immune system. Modifications
      in its composition are associated with problems such as obesity or inflammatory
      bowel diseases. Antibiotics are known to influence the intestinal microbiota but
      other environmental factors such as cigarette smoking also seem to have an impact
      on its composition. This influence might partly explain weight gain which is
      observed after smoking cessation. Indeed there is a modification of the gut
      microbiota which becomes similar to that of obese people with a microbiotical
      profile which is more efficient to extract calories from ingested food. These new
      findings open new fields of diagnostic and therapeutic approaches through the
      regulation of the microbiota.

PMID- 26211090
TI  - [International Health Electives in developing countries for medical and nursing
      students: four experiences from French-speaking Switzerland].
AB  - International Health Electives performed in developing countries by students of
      medical and nursing schools from industrialized nations have recently become a
      highly valued element in curricula of medical and nursing schools. We report here
      four examples of such electives developed over the years at the Faculties of
      medicine of Geneva and Lausanne, one involving both medical and nursing school
      students. These electives foster enthusiasm and commitment among students and
      host institutions abroad. A selective review of the literature highlights the
      many positive aspects of such electives for the professional and personal
      development of students. It also emphasizes what the host institutions can gain
      from these electives provided the latter are organized in a balanced partnership
      and that the students receive a careful preparation to avoid possible pitfalls.

PMID- 26211091
TI  - [Replace the "Little ethics" by a "Great Ethics" ].

PMID- 26211092
TI  - [Oocytes, spermatozoa, etc...The dangers of a radio search].

PMID- 26211093
TI  - [Will hepatitis C be eradicated in France by 2025?].

PMID- 26211094
TI  - [What is the role of oral steroids in the treatment of acute sciatic?].

PMID- 26211096
TI  - [The path of aging].

PMID- 26211095
TI  - [Bertrand Jordan, molecular biologist and the Gospel of John].

PMID- 26211097
TI  - Effect of Tri-sa-maw recipe on gastrointestinal regulation and motility. .
AB  - BACKGROUND: Tri-sa-maw recipe is comprised ofequal proportions of three herbal
      fruits, including Terminalia chebula Retz., Terminalia sp. and Terminalia
      bellirica Roxb. The traditional use of this recipe has been reported as a
      medication for fever; expectorant, relief of tightness in the stomach, laxative
      and antidiarrheal agent. OBJECTIVE: To study the effects of Tri-sa-maw recipe
      extract on gastrointestinal tract in both in vitro and in vivo. MATERIAL AND
      METHOD: Gastrointestinal effect of Tri-sa-maw recipe was studied by using two in
      vivo models (gastric emptying, gastrointestinal transit) and in vitro isolated
      guinea pig ileum experiment. RESULTS: Tri-sa-maw recipe showed both stimulatory
      and inhibitory effects on the stomach function. Not only did the extract at the
      dose of 1,000 mg/kg inhibit the gastric emptying time, but also stimulate the
      movement of the digestive tract by increasing the mobility of charcoal. In the
      isolated guinea pig ileum experiment, the extract at low concentration (0.1
      ng/mL) induced the contraction of isolated guinea pig ileum. However the
      stimulation effect on contractions of isolated guineapig ileum was very much
      decreased at the high concentration (0.2-1 ng/mL) of the extract. CONCLUSION: The
      findings of this study support to traditional uses of Tri-sa-maw recipe as a
      laxative and antidiarrheal agent.

PMID- 26211098
TI  - Acute and sub-chronic toxicity of Tri-sa-maw recipe in rats.
AB  - BACKGROUND: Tri-sa-maw recipe is a botanical preparation comprised of equal
      proportions ofthe three herbalfruits, namely Terminalia chebula Retz., Tenninalia
      sp. and Terminalia bellirica Roxb. This recipe is used for antipyretic,
      expectorant, periodic maintenance, and relieving stomach tight. OBJECTIVE: To
      evaluate the acute and sub-chronic toxicities of Tri-sa-maw recipe extract in
      rats. MATERIAL AND METHOD: In the present study of acute toxicity, a single oral
      dose 5,000 mg/kg of Tri-sa-maw recipe extract was administered to rats. Sub
      chronic toxicity was studied by the daily oral administration ofthe extract at
      the doses of 600, 1,200 and 2,400 mg/kg body weight for consecutive 90 days.
      RESULTS: Tri-sa-maw recipe extract at the dose of 5,000 mg/kg showed no signs of
      differences as compared to the control rat. No abnormalities were found in the
      sub-chronic toxicity study; none of the parametersfor body and organ weights,
      hematol- ogy, blood chemistry, necropsy, and histopathology showed any
      differences between the control and all treatment groups. CONCLUSION: Tri-sa-maw
      recipe extract did not significantly cause acute toxicity or sub-chronic toxicity
      in rats.

PMID- 26211099
TI  - Analgesic and antipyretic activity of Tri-sa-maw recipe.
AB  - BACKGROUND: Tri-sa-maw recipe is composed of equal proportions of the three
      fruits including Terminalia chebula Retz., Terminalia sp. and Terminalia
      bellirica Roxb. In Southeast Asia, these fruits are used as both food and
      medicine. In Thai traditional medicine, Tri-sa-maw recipe is well known for
      treating fever, expectorant, periodic maintenance, and tight stomach relief
      OBJECTIVE: To study anti-inflammatory, analgesic and antipyretic activities of
      Tri-sa-maw recipe in experimental animals. MATERIAL AND METHOD: The anti
      inflammatory study was conducted by two experimental models; ethyl
      phenylpropiolate- induced ear edema and carrageenin-induced paw edema. For
      analgesic activity, the pain was induced by acetic acid or heat. In addition,
      yeast-induced hyperthermia was performedfor the study of antipyretic activity.
      RESULTS: The results showed that Tri-sa-maw recipe extract reduced ear edema
      ofrat induced by EPP but did not inhibit acute inflammation in the carrageenin
      inducedpaw edema. However the extract at the doses of 300-1,200 mg/kg was able to
      inhibit the acetic acid-induced writhing response, but not the heat-induced pain.
      This result suggests the peripheral effect of its analgesic activity, which
      inhibits the biosynthesis, and/or release of some pain mediators. Finally, oral
      administration ofthe extract at the dose of 1,200 mg/kg body weight effectively
      reduced the hyperthermia, which possibly is due to the inhibition of
      prostaglandins. CONCLUSION: The present study has clearly demonstrated both
      analgesic and antipyretic activities of Tri-sa-maw recipe.

PMID- 26211100
TI  - An investigation of antimicrobial and wound healing potential of Allium
      ascalonicum Linn.
AB  - BACKGROUND: The pharmacological properties of Allium ascalonicum Linn., commonly
      called shallot, have been reported as including those that are antibacterial and
      antioxidant. OBJECTIVE: The present study aimed to evaluate the antimicrobial
      effect and wound-healing activity ofthe ethanolic extracts of Allium ascalonicum
      Linn. (AAE). MATERIAL AND METHOD: The antimicrobial activity of AAE was tested in
      vitro against using the disc diffusion method and a broth micro-dilution
      technique to determine the minimal inhibition concentrations (MIC) and the
      minimal microbicidal concentrations (MMC). Wound-healing activity of the extract
      was performed on rat test subjects. RESULTS: The AAE showed potential
      antimicrobial activity by inhibiting gram-positive bacteria Staphylococcus
      epidermidis and Bacillus subtilis ATCC 6633. MIC and MMC varied from 25-50 mg/ml
      and 25-200 mg/ml, respectively. After surgery 14 days, wound contractions
      oftreated groups and standard group were 78.61 +/- 1.20%, 78.55 +/- 1.93% and
      100%, respectively; but, in the control group, wound contraction was 64.90 +/-
      3.55%. Histological studies showed the complete epidermis and found the collagen
      fibers and fibroblasts as similar appearance as standard group in dermis. The
      results of histological evaluation have confirmed remarkable wound-healing
      activities of AAE. CONCLUSION: Taken together the present study provides evidence
      that AAE extract processes antimicrobial and wound-healing activities.

PMID- 26211101
TI  - Mental health and quality of life among Thai psychiatrists. . .
AB  - OBJECTIVE: To survey the mental health and quality of life among Thai
      psychiatrists. MATERIAL AND METHOD: This cross-sectional descriptive study
      included all Thai psychiatrists. The postal survey was mailed out to
      allpsychiatrists. The questionnaires consisted ofthree parts: demographic data,
      the WHO Quality ofLife-BREF-Thai version and the Symptom Checklist 90-Revised
      Thai edition. Correlation analysis was set up at 95% confident interval and
      p<0.05. RESULTS: Response rate was 28%from all 650 psychiatrists. The respondents
      described normal state of mental health but female psychiatrists had tended more
      to suppress the psychological symptoms than male psychiatrists. The mental
      problem that might most disturb male psychiatrists under stress condition was
      obsessive-compulsive symptoms. Female psychiatrists tended to be disturbed when
      distressed by (1) anxiety, (2) somatization, (3) phobia, (4) depression, and (5)
      paranoia, respectively. The quality of life (QOL) of most psychiatrists was in
      the average level (77.5%). The older (>40 years old) psychiatrists had higher QOL
      than younger psychiatrists significantly (p = 0.027). QOL correlated
      significantly with not getting enough support from workplace (p = 0.007),
      colleagues (p = 0.026), lack of consultancy (p = 0.011) and lowjob satisfaction
      (p = 0.007). Better life quality in psychiatrists' group had better QOL in social
      relationships and satisfaction with the environment. CONCLUSION: Thai
      psychiatrists had mental health status within normal range. Male psychiatrists
      had obsessive-compulsive traits in stress response, but female psychiatrists had
      anxiety and somatization traits. Thai psychiatrists'quality of life was on the
      average level and most of them satisfied with their QOL.

PMID- 26211102
TI  - In vitro enhancement of doxorubicin genotoxic activities and interference with
      cell cycle delay by Plumbago indica root ethanolic extract in human lymphocytes.
AB  - BACKGROUND: Combinations of modern medicines with herbal medicines are being
      developedfor more effectiveness. Data on the safety and drug-herb interactions
      are needed to be clarified. Ethanolic extract of Plumbago indica root (EEPIR) is
      medicinally usedfor cancer treatment in Asian traditional medicine. However its
      mechanism of action is still inconclusive. Our previous study demonstrated that
      EEPIR was genotoxic and induced cell cycle delay in human lymphocytes in vitro.
      OBJECTIVE: To investigate genotoxic potency and interference with cell cycle of
      EEPIR in combination with doxorubicin (DXR), a standard chemotherapeutic agent,
      in human lymphocytes by in vitro sister chromatid exchange (SCE) assay. MATERIAL
      AND METHOD: Human lymphocytes were pretreated with EEPIR at 6.25-100
      mcg/mlfollowed by DXR (0.1 mcg/ml). SCE levels and cell cycle kinetics were
      evaluated. RESULTS: EEPIR pretreatments (6.5-50 mcg/ml) significantly enhanced
      genetic damage induced by DXR (p<0. 05). Delaying of the cell cycle was detected
      and related to EEPIR concentration. EEPIR at 100 mcg/ml, on the contrary, did not
      enhance DXR-induced genotoxicity but tended to lower genotoxicity compared to DXR
      treatment alone. It significantly delayed cell cycle the most (p<0.05).
      CONCLUSION: EEPIR pretreatments at proper doses enhanced genotoxic damage induced
      by DXR in human lymphocytes. Delaying cell cycle by EEPIR could lower that
      potency. Usage of EEPIR, therefore, should be adjusted for safety. Combination of
      EEPIR with DXR might be usefulfor more efficient cancer treatment with less DXR
      toxicity. Further in vivo study is needed to support this in vitro evidence.

PMID- 26211103
TI  - Depression and burden among caregivers of children with autistic spectrum
      disorder.
AB  - OBJECTIVE: To study depression prevalence and burden among caregivers of children
      with autistic spectrum disorder and the related factors. MATERIAL AND METHOD:
      This is a cross-sectional descriptive study. Measures included questionnaires,
      CES-D and burden interview. Patients' diagnoses andfunctions were obtainedfrom
      childpsychiatrists and developmental pediatricians responsible for the patients.
      RESULTS: There were 51 participants. The depression prevalence was 5.9%.
      Concerning the burden, 45.1% ofthe participants reported little or no burden, and
      45.1% reported mild to moderate burden. Only 7.8% and 2.0% experienced moderate
      to severe and severe burdens, respectively. There was a significant positive
      correlation between depression and burden (p = 0.012). Significant correlations
      were also observed between burden and months after diagnosed, the number
      ofpatient' problems and the number of hours that caregiver spent with patient per
      day. Moreover the burden was significantly associated with patient's
      communication problems and patient's inappropriate odd repetitive behaviors (p<0.
      05). CONCLUSION: The prevalence of depression in and severe burden on caregivers
      of autistic childrenfrom the present study was low. Factors related to the burden
      were months after diagnosed, the number of patient's problems, the number of
      hours that caregiver spent with patient, patient's communication problems and
      inappropriate or odd repetitive behaviors.

PMID- 26211104
TI  - A comparison of precorneal tear film pre and post pterygium surgery. .
AB  - BACKGROUND: Precorneal tear film was altered in pterygium eye and may be improved
      after pterygium removal. OBJECTIVE: To compare Schirmer's test results and tear
      breakup time before and after pterygium surgery. MATERIAL AND METHOD: Forty
      patients, aged between 30 and 77 years were enrolled in this study; one pterygium
      surgery eye was observed per patient. A paired t-test was used to compare
      Schirmer's test results and tear breakup time pre pterygium excision and one
      month post-operation. RESULTS: There were no statistically significant
      differences in Schirmer's test results and tear breakup time between pre and one
      month post-operation. The mean +/- standard deviations of Schirmer's test results
      before and one-month after pterygium surgery were 9.2 +/- 4.3 and 10.0 +/- 6.3
      millimeters, respectively (p = 0.30), and those results for tear breakup time
      were 7.5 +/- 3.0 and 7.9 +/- 3.1 seconds, respectively (p = 0.44). CONCLUSION:
      Pterygium removal may not have any effect on Schirmer's test results and tear
      breakup time one-month post- surgery.

PMID- 26211105
TI  - Cognitive enhancement effects of Bacopa monnieri (Brahmi) on novel object
      recognition and neuronal density in the prefrontal cortex, striatum and
      hippocampus in sub-chronic phencyclidine administration rat model of
      schizophrenia.
AB  - BACKGROUND: Cognitive deficit is a significant problem, which finally occurs in
      all schizophrenic patients. It can not be attenuated by any antipsychotic drugs.
      It is well known that changes of neuronal density are correlated with learning
      and memory deficits. Bacopa monnieri (Brahmi), popularly known as a cognitive
      enhancer; might be a novel therapeutic agentfor cognitive deficit in
      schizophrenia by changing cerebral neuronal density. The objective of this study
      was to determine the effects of Brahmi on attenuation at cognitive deficit and on
      the neuronal density in the prefrontal cortex, striatum and cornu ammonis
      subfield 1 (CA1) and 2/3 (CA2/3) of hippocampus in sub-chronic phencyclidine
      (PCP) rat model of schizophrenia. MATERIAL AND METHOD: Rats were assigned to
      three groups; Group-1: Control, Group-2: PCP administration and Group-3: PCP +
      Brahmi. Rats were testedfor cognitive ability by using the novel object
      recognition test. Neuronal density from a serial Nissl stain sections ofthe
      prefrontal cortex, striatum and hippocampus ofrat model ofschizophrenia were
      measured by using Image ProPlus software and manual counting. RESULTS: Sub
      chronic administration of PCP results in cognitive deficits in novel object
      recognition task. This occurred alongside significantly increased neuronal
      density in CA1. The cognitive deficit was recovery to normal in PCP + Brahmi
      group and it occurred alongside significantly decreased neuronal density in CA1.
      On the other hand, significantly increased neuronal density was observed in CA2/3
      of PCP + Brahmi group compared with PCP alone. CONCLUSION: Brahmi is a potential
      cognitive enhancer against schizophrenia. It reduces neuronal density, most
      likely glutamatergic neuron, which results in neuronal toxicity and cognitive
      deficit. Therefore, Brahmi has cognitive enhancement effect by reducing
      glutamatergic neuron in CAI. Moreover, it also has neurogenesis effect in CA2/3,
      which is needed to be investigated in the further study.

PMID- 26211106
TI  - Occupational safety and health management among five ASEAN countries: Thailand,
      Indonesia, Malaysia, Philippines, and Singapore.
AB  - Occupational safety and health is one of important issues for workforce movement
      among ASEAN countries. The objective was to study laws, main agencies, and law
      enforcement regarding occupational safety and health in Thailand, Indonesia,
      Malaysia, Philippines, and Singapore. This documentary research covered laws,
      main agencies' duties, and occupational safety and health law enforcement in
      Thailand, Indonesia, Malaysia, Philippines, and Singapore. Thailand has its
      Occupational Safety, Health, and Work EnvironmentAct 2011. Its main agency was
      Department of Labor Protection and Welfare. Indonesia had WorkSafety Act (Law No.
      1, 1970). Its main agency was Department of Manpower and Transmigration. Malaysia
      had Occupational Safety and Health Act (OSHA) 1994. Its main agency is the
      Department of Occupational Safety and Health. The Philippines has its
      Occupational Safety and Health Standards. Its main agency was Department ofLabor
      and Employment. Singapore has its Workplace Safety and Health Act 2006. Its main
      agency is Occupational Safety and Health Division. Occupational safety and health
      law enforcement among each county covers work environment surveillance, workers'
      health surveillance, advice about prevention and control of occupational health
      hazards, training and education of employers and employees, data systems, and
      research. Further in-depth surveys of occupational safety and health among each
      ASEAN county are needed to develop frameworks for occupational safety and health
      management for all ASEAN countries.

PMID- 26211107
TI  - Total endoscopic thyroidectomy via a unilateral axillo-breast approach with two
      spatula-shaped wires each attached to the end of an endoscopic aspirator and a
      retractor-shaped wire.
AB  - OBJECTIVE: With a total endoscopic thyroidectomy, it is extremely important to
      establish sufficient space. To solve this problem, the author has developed a new
      device, which is a retractor-shaped wire for retraction of the strap muscles
      without an additional port. Atraumatic tools for pushing and pulling without
      breaking the thyroid are necessary because intra-operative bleeding is afrequent
      cause of conversion to open procedure. To solve this problem, the author has
      developed a new device, which is a spatula-shaped wire that is attached to the
      end ofan endoscopic aspirator This spatula-shape wire can be used to push and
      pull the thyroidfirmly without it breaking of thyroid tissue. MATERIAL AND
      METHOD: From 15 March 2011 to 15 April 2014, the author used these new devices in
      18 consecutive patients who were considered eligible for the surgery. RESULTS:
      Lobectomy with isthmusectomy was performed on 12 patients (67%). Through the same
      incisions, a subtotal thyroidectomy was accomplished infour cases (22%) and the
      Hartley-Dunhillprocedure was performed on two cases (11%). The mean specimen
      weight on the histological report was 33.12 grams (range, 8.4 to 79.6 grams). Two
      cases of left lobectomy with isthmusectomy had previously had a conventional
      right lobectomy. There was one case with the same procedure which had had a
      suspicious nodule on Graves'disease treated with radioactive iodine one and a
      halfyears ago. There was a case of chronic thyroiditis in one Dunhill procedure.
      No hemorrhage occurred during the procedures. There were three cases of
      subcutaneous bruising. There were no other complications detected and no cases
      were converted to open thyroidectomy. CONCLUSION: Thyroid surgery with the
      unilateral axillo-breast approach and the new tools is safe and effective. These
      tools make it possible to operate on larger thyroid lesions and perform thyroid
      surgery on patients who have had traditional thyroid surgery, Graves' disease,
      and chronic thyroiditis.

PMID- 26211108
TI  - Perception of social networking benefits in the support of a PBL module according
      to students' performance levels.
AB  - BACKGROUND: The use ofsocial networking to all levels of medical teaching as a
      communication tool between instructors and students has drawn much interest and
      increased usage. As Facebook is one of the most popular social networking sites
      among students, a Facebook page has been used in the Genitourinary System problem
      based learning (PBL) course at the Faculty of Medicine, Thammasat University in
      the year 2014. OBJECTIVE: The objective of this work is to study the perception
      ofusing a Facebook page to support PBL in an integrated pre- clinical year
      course. MATERIAL AND METHOD: The Genitourinary System course committee introduced
      Facebook page to the 2"d year medical students who enrolled and instructors
      involved in the course. At the beginning ofthe course, the objectives ofFacebook
      page setting were informed as follows: 1) public relations, 2) channelfor
      questions and responses to address curiosities between students and instructors,
      3) learning stimulation and 4) supporting good relationship between course
      coordinators and students. The participants consisted of 177 students who
      voluntarily allowed their opinion to be used in analysis and dissemination after
      completing a questionnaire about using the Facebook page in PBL at the end. A
      Likert scale was used to determine satisfaction scores for nine questions.
      Finally, the mean satisfaction was compared for each question and for students
      with different academic performances (great, good, fine, weak). RESULTS: The
      students liked the page (averaged satisfaction score 4.64) and wanted it to
      continue to be used in coursework (4.63), especiallyfor students at mid-level
      when compared to students with great performances (p<0.05). It was beneficial in
      allowing questions to be directed to instructors, both in lecture learning (4.54)
      and SDL (4.35), and lessened the time it took to understand content in SDL
      (4.03). However, although it did notcreate stress (2.10), students had not
      madefull use of it, as much as they could (3.25), as they were not able study all
      posts in detail (3.68). Therefore, if the Facebook pages were developed for
      students to study in more detail, it would enhance its benefits as SDL stimulus
      (4.09). CONCLUSION: Using social networking, particularly Facebook pages,
      achieved all the four the stated objectives. Since this was the first time social
      networking was applied, some of faculty members had concern that their personal
      information would be disseminated to the public. Moreover there was still minimal
      knowledge of sharing among students. The Facebook "closed group" with a good
      protective system may be an interesting option to enhance effectiveness in
      integrated PBL-styled courses.

PMID- 26211109
TI  - Comparison of hyaluronan binding assay scores of spermatozoa using swim-up
      techniques and density gradient centrifugation.
AB  - OBJECTIVE: To compare the hyaluronan binding assay (HBA) scores of sperm
      preparation using two different methods, the swim-up technique and density
      gradient centrifugation (DGC). MATERIALS AND METHOD: This experimental study used
      semen specimens from 54 volunteer subjects with normal semen analysis according
      to the 2010 World Health Organization criteria. Each semen specimen was split
      into two portions: one was prepared using the swim-up method and the other the
      DGC method. The prepared sperm were counted in the sperm-HBA slide to determine
      bound and unbound motile sperm. The HBA scores between the two methods were
      compared using matched analysis. RESULTS: The HBA scores by either preparation
      method were >80%. There was no statistically significant difference in HBA scores
      between the swim-up preparation [median 97%, interquartile range (IQR) 94, 98]
      and density gradient centrifugation [median 96%, IQR 95, 98] (p = 0.96). Ten
      ofthe 54 specimens received the same HBA scores following the two methods and
      none differed by more than +/- 7%. CONCLUSION: Both preparation methods gave high
      HBA scores with no apparent difference in the proportions between methods.

PMID- 26211110
TI  - Mini version of the pediatric asthma quality of life questionnaire (MiniPAQLQ):
      validity among Thai asthmatic children.
AB  - BACKGROUND: The assessment of the quality of life among patients and their
      parents is increasingly recognized as an important chronic disease such as
      asthma. OBJECTIVE: The present study assessed the validity and reliability of the
      Thai Mini PAQLQ in Thai asthmatic children by comparison with the PAQLQ. MATERIAL
      AND METHOD: The authors performed a 9-week Descriptive cross sectional study. The
      mini PAQLQ (Thai version) consists of11 items which are categorized into
      symptoms, activities, emotions. Cronbach 's alpha was used to test for internal
      consistency reliability. The Pearson's correlation co-efficients was used to test
      Criterion validity. RESULTS: 58 patients, aged 7-17 years were recruited in the
      study. 45 patients completed the study. The mean age ofpatients was 10.5 +/- 2.7
      years. The intraclass correlation between PAQLQ andMiniPAQLQfor total, activities
      and symptoms were moderately strong except in emotion domain (ICC = 0.65). The
      correlations between the PAQLQ and MiniPAQLQ were 0.80-0.72. Both quality of life
      questionnaires correlated strongly with the asthma control questionnaire but not
      with PEFR. CONCLUSION: The MiniPAQLQ is valid and reliable when compared to the
      PAQLQ. It can be used with confidencefor monitoring in a pediatric asthma clinic.

PMID- 26211111
TI  - High pre-pregnancy body mass index and the risk of poor obstetrics outcomes among
      Asian women using BMI criteria for Asians by World Health Organization Western
      Pacific Region (WPRO): a large cohort study.
AB  - OBJECTIVE: To evaluate the effects of high pre-pregnancy body mass index (BMI) on
      the risk ofpoor obstetric outcomes among Asian women using BMI criteria by
      Regional Office for the Western Pacific Region of WHO (WPRO). MATERIAL AND
      METHOD: The present study was a retrospective cohort. Subjects of live birth
      singletons who had full term delivered atfour tertiary care centers, teaching
      university hospitals between January and December 2012 were enrolled. All
      pregnant women with pre-pregnancy BMI 18.5 kg/m2 or over were recruited and
      categorized into two groups, normal BMI and high BMI Level of BMI at 18.5-22.9
      kg/m2 was defined normal BMI, and level at or over than 23 kg/M2 was defined as
      high BMI, respectively. The association between high pre-pregnancy BMI and poor
      adverse pregnancy outcomes were evaluated. RESULTS: Two thousands seven hundred
      and thirty-three pregnant women were recruited. Normal and high pre-pregnancy BMI
      women were 1,840 and 893, respectively. The average age was 2 7.81 +/- 5.67 and
      29.48 +/- 13.03 years old respectively. Most ofsubject were primigravida. Mean
      BMI of normal group and high BMI group were 20.2 7 +/- 1.42 and 26.66 +/- 3.45
      kg/ m2, respectively. In multivariate analysis, high pre-pregnancy BMI pregnant
      women have significantly higher adjusted risk ratio for gestational diabetes
      mellitus and preeclampsia, induction of labor prolong second stage of labor,
      including, caesarean delivery or obstetrics procedures (RR 1.54, 95% CI 1.30
      1.84, RR 1.17, 95% CI 1. 12-1.23, RR 1.41, 95% CI 1. 04- 1.90, RR 1.28, 95% CI
      1.11-1.48 and RR 1.17, 95% CI 1.05-1.27, respectively). In addition, the adjusted
      risk ratio of postpartum hemorrhage and neonatal macrosomia were significantly
      increased (RR 1.86, 95% CI 1.01-3.43 and RR 1.46, 95% CI 1.28-1.65,
      respectively). CONCLUSION: This evidence strongly suggested that high pre
      pregnancy BMI using WPRO criteria increased the risk of pregnancy complications
      and adverse pregnancy outcomes. This study was one of the largest studies among
      Asian populations.

PMID- 26211112
TI  - Validation of the Thai version of Bergen Facebook addiction scale (Thai-BFAS). .
AB  - OBJECTIVE: To determine the validity ofthe Thai version ofthe Bergen
      FacebookAddiction Scale (Thai-BFAS) using Facebook addiction screening in Thai
      high school students. MATERIAL AND METHOD: The original BFAS was authorized for
      translation and validation in Thai. After content validity and usability were
      approved by three Thai psychiatrists, the Thai-BFAS was adjusted again by the
      authors and back translated by an English expert. Thisfinal version was
      investigated using the internal consistency method among 874 high schools
      students in Bangkok, Chiang Mai, Ubon Ratchathani and Songkhla, and confirmatoy
      factor analysis (CFA) was employed to prove that the six-component model could be
      representative of addiction behaviors. In addition, test-retest reliability was
      performed separately among 30 pilot high school students in Bangkok. RESULTS: The
      Thai-BFAS has six items, which are each scored on a 5-point scale with total
      score ranges from 0 to 24; the cutoff score for Facebook addition stands at least
      12 points. The Cronbach s alpha coefficient was 0.91 (95% CI; 0.90, 0.92) and the
      inter-class correlation coefficient was 0.80 (95% CI; 0.49, 0.92). The CFA showed
      that the six items accurately represent the six-component model of addiction such
      as salience, mood modification, tolerance, withdrawal, relapse and conflict.
      CONCLUSION: The Thai-BFAS is consistent as a screening testfor Facebook addiction
      among high school students due to good reliability and validity. It also conforms
      well to the original version. The six items in the Thai-BFAS are a good
      representation of the addiction behaviors. Further studies should be undertaken
      in cases of sensitivity and specificity when compared with other similar tests of
      addiction as well as in various additional populations and circumstances.

PMID- 26211113
TI  - Homelessness among the Elderly in Bangkok Metropolitan.
AB  - The combination between quantitative and qualitative research, "Homelessness
      among the Elderly in Bangkok Metropolitan" aimed to study causes of homelessness,
      patterns of living, problems, health status, social and health needs. Purposive
      sampling of 60 older homeless people could be divided into two groups; temporary
      and permanent homeless. Causes of homelessness were health problems, money
      problems, family background, emotional management, cultural sensitivities,
      limitation of extended family, financial management, political control, and
      domestic violence. Their living problems included:financial insecurity, police
      suppression, social and medical services, attacks from the young generations,
      sexual harassment, stealing, and social hierarchy of homelessness. 63.3% reported
      having hearing problems and a peptic ulcer before becoming homeless. These
      evolved into musculo-skeletal problems, accident-injuries, and skin diseases. 95%
      performed ADL/IADLs independently, 78.3% were depressed, 5% diagnosed with severe
      stress depression. 70% rated themselves happier than the rest ofthe population,
      and 75% were identified as having normal cognition. 58.3% had a good relationship
      with a religious network, 55% still had some contacts with theirfamily members.
      More than 90% indicated that they were satisfied, could sustainin a life on the
      street, were happy with theirfreedom, liked being close to green areas, learned
      about human life,fulfilled the dhamma, and felt close to the king.

PMID- 26211114
TI  - Health-related quality of life and functional outcomes in ankle arthritis
      patients based on treating with and without total ankle replacement surgery.
AB  - BACKGROUND: Little is known about health-related quality of life and functional
      outcomes in candidate patients with indications for total ankle replacement (TAR)
      when compared to patients without indications. This study is to compare the
      quality of life and functional outcomes in patients who have ankle arthritis and
      are with and without indicationsfor TAR. MATERIAL AND METHOD: An evaluation was
      conducted on 40 patients who had developed ankle arthritis from various causes.
      Forty patients were divided into two groups in accordance with their indications
      for TAR; the TAR-indicated group (11 patients) and the non-TAR indicated group
      (29 patients). Medical records of each patient were reviewed to collect pre-
      treatment visual analogue scale (VAS-pain) scores, visual analogue scale foot and
      ankle (VAS-FA) scores, health-related quality of life scores as ascertained from
      short-form 36 (SF-36), and baseline data. RESULTS: VAS-pain, VAS-FA, and SF-36
      scores were insignificantly poorer in TAR-indicated group (p>0.05). There were no
      significant differences in scores among the three groups of treatment as non
      operative treatments, joint-preserving treatments, and joint-sacrificing
      treatments or between TAR-indicated group and arthrodesis group (p>0.05). There
      were significant correlations between VAS-pain and VAS-FA scores (Pearson's r
      correlation-coefficient (r) = -0.389; p = 0.019) or between VAS-FA and SF-36
      scores (r = 0.564; p<0.01). There were no significant correlations between VAS
      pain and SF-36 scores (p>0.05). Only SF-36 scores were significantly negative
      correlated with radiographic grades in Takakura (r = -0.382; p 0.015) and the
      author's (r = -0.378; p = 0.016) classifications. CONCLUSION: Quality of life and
      functional outcomes in candidate patients with indications for TAR was
      insignificantly poorer than those in the patients without indications or patients
      in arthrodesis subgroup. Poorer radiographic grades of ankle arthritis were
      significantly correlated with poorer quality of life, which is reflected via SF
      36 scores.

PMID- 26211115
TI  - Snoring and sleep problems in children with and without allergic rhinitis: a case
      control study.
AB  - OBJECTIVE: To compare the sleep problems between children with and without
      allergic rhinitis (AR). MATERIAL AND METHOD: A case-control study was conducted
      in 65 children aged 6-15 years with allergic rhinitis and 104 control subjects
      matched individually by age, height and weight. Cases were recruited from the
      Pediatric Allergy Clinic at Thammasat University Hospital. The selection of cases
      was based on clinical history, physical examination and skin prick test. Matched
      healthy control children were recruited from the Thammasat primary school.
      Children and their caregivers who usually sleep with them completed the
      questionnaire. RESULTS: 86.2% of allergic rhinitis was classified as persistent
      rhinitis and 63.1% had moderate to severe disease. The most common presenting
      symptom was nasal blockage (66.2%). Allergic rhinitis patients had significant
      sleep problems with snoring, sleep apnea, restless, night sweating, mouth
      breathing, dry throat, morning headache, falling asleep in class, difficulty in
      waking up and not refreshed in the morning (p<0.05). Patients who categorized as
      blockers had significantly more restless sleep and dry mouth on waking up
      compared to that of non-blockers (p<0.05). CONCLUSION: There was a higher
      prevalence of sleep problems in children with AR then those without AR.

PMID- 26211116
TI  - Study of basic-life-support training for college students.
AB  - OBJECTIVE: To study about attitude and knowledge regarding basic-life-support
      among college students outside medical system. MATERIAL AND METHOD: The cross
      sectional study in the emergency department of Thammasat Hospital. The authors
      included college students at least aged 18 years old and volunteers to be study
      subjects. The authors collected data about attitudes and knowledge in performing
      basic-life-support by using set of questionnaires. RESULTS: 250 college students
      participated in the two hours trainingprogram. Most ofparticipants (42.4%) were
      second-year college students, of which 50 of 250 participants (20%) had trained
      in basic-life-support program. Twenty-seven of 250 participants (10.8%) had
      experience in basic-life-support outside the hospital. Most of participants had
      good attitude for doing basic-life-support. Participants had a significant
      improved score following training (mean score 8.66 and 12.34, respectively,
      p<0.001). Thirty-three of 250 participants (13.2%) passed the minimum score
      before trained testing, whereas 170 of 250 participants (68%) passed the minimum
      score after trained testing. CONCLUSION: With accurate knowledge and experience,
      lay rescuers may have more confidence tope7form basic-life-support to cardiac
      arrest patient. The training program in basic-life-support has significant impact
      on knowledge after training.

PMID- 26211117
TI  - Incidence of steroid induced-ocular hypertension in postoperative pterygium
      excision.
AB  - BACKGROUND: Steroid eye drops were widely used for suppression ocular
      inflammation in many conditions. Unfortunately, steroid eye drops can cause many
      side effects; the important one was steroid-induced ocular hypertension that may
      progress to seconday glaucoma. OBJECTIVE: To evaluate incidence ofsteroid
      responder following topical dexamethasone use after pterygium excision with
      amniotic membrane graft. DESIGN: Prospective descriptive study. MATERIAL AND
      METHOD: The present study was designed to evaluate intraocular pressure (IOP)
      change from topical dexamethasone eye drops in postoperative pteiygium excision
      with amniotic membrane grafting. The subjects were routinely prescribed CD-oph (1
      mg/ml dexamethasone sodium phosphate, 5 mg/nd chloramphenicol and 0.25 mg/ml
      Tetrahydrozaline hydrochloride) eye drops every 1 hour for 1 week, then every 2
      hours until 1 month, then four times daily until 3 months postoperatively. The
      subjects were measured IOP at I week, 1 month, and 3 month postoperatively by
      applanation tonometer The steroid responder was defined as an elevation ofIOP at
      least 10 mmHgfrom preoperative. The incidence was calculated, trend of IOP rising
      and timing of peak IOP were assessed. RESULTS: Ofthe 62 patients, 6 were
      diagnosed as steroid responders (IOP >10 mmHg), 9.68% (95% CI 3.6-19.9). Mean of
      peak IOP rising was 4.02+/-3.18 mmHg with maximum IOP rising was 11 mmHg. 4 of 6
      cases of steroid responders occur at 3 month postoperative, 2 another cases occur
      at 1 week and I month postoperative. Most of the subjects had IOP rising in range
      of 0-4 mmHg (62.90%), follow by 5-9 mmHg (2 7.42%), and > 10 mmHg (9.68%),
      respectively. Maximum IOP mostly in range of 16-20 mmHg (43.55%), follow by 11-15
      mmHg (40.32%), 21-25 mmHg (9.68%), and more than 26 mmHg (6.45%), respectively.
      45.16% of subjects showed the time of peak lOP at postoperative 1 month.
      CONCLUSIONS: Steroid response is a common problem in steroid use, especially with
      topical steroid eye drops. The incidence of steroid responderfrom this study was
      9.68%, which may differ from the others by type, frequency of the topical steroid
      used, including criteria to diagnosis of steroid responder

PMID- 26211118
TI  - Childhood disintegrative disorder: a case report.
AB  - Childhood Disintegrative Disorder (CDD), a clinical syndrome distinctfrom
      childhood autism, is a rare unremittingly pervasive developmental disorder
      resultingfrom disintegration ofmentalfunctions and progressive neurological
      abnormality. This rare condition is characterized by regression or loss
      ofpreviously acquired language and social skills after a period of at least 2
      years of normal development. This report presenting a case of a 10-year-old boy
      who presented with normal development until 3-4 years of age followed by
      gradually developmental deterioration in previously acquired social skills,
      language and intellectual functions with aberrant behaviors suggestive of
      childhood disintegrative disorder This case is reported as a very rare case and
      there is no previous official report in Thailand.

PMID- 26211119
TI  - Primary perianal Paget's disease with focal adenocarcinoma, signet-ring cell
      differentiation and unusual immunohistochemical expression: a case report.
AB  - Perianal Paget's disease is an uncommon intraepidermal carcinoma characterized by
      the presence ofPaget cells. It usually affects older patients and commonly
      presents as chronic perianal pruritus with scaly plaques. The disease is
      categorized into primary perianal Paget's disease ofcutaneous origin and
      secondaryperianal Paget's disease, which is due to extension of a visceral
      malignancy such as that of the anorectum or colon. Cytokeratin 7 (CK7),
      cytokeratin 20 (CK20), and gross cystic disease fluid protein-15 (GCDFP15)
      expression are useful for differentiation between these two types. A tumor
      immunohistochemical profile of CK7+/CK20-/GCDFP15+ suggests the primary type,
      whereas CK7+/CK20+/GCDFP15- suggests the secondary type. The expression of caudal
      homeobox 2 (CDX2) suggests the secondary type from anorectal or colonic
      adenocarcinoma. However, approximately one- third of patients without visceral
      malignancy have a tumor that is CK7+/CK20+/GCDFP15-. Two percents of primary
      perianal Paget ' disease can express CDX2. The author reports a case ofan 86-year
      old man who presented with chronic perianalpruritus and a scaly plaque. A skin
      biopsy showed intraepidermal Paget cells with immunohistochemical profile of
      CK7+/CK20+/GCDFPJ5-/CDX2+. Initially, secondary perianal Paget's disease from
      colorectal adenocarcinoma was suspected. However, extensive investiga- tions
      found no visceral malignancy. The patient underwent wide excision of the perianal
      skin. Pathological examination showed diffuse intraepidermal Paget cells
      withfocal dermal invasion by intestinal-type adenocarcinoma and signet-ring cell
      differentiation. In conclusion, thefinal diagnosis was primary perianal Paget's
      disease withfocal adenocarcinona and signet- ring cell differentiation. The
      disease was consistent with primary perianal Paget's disease, because no visceral
      malignancy was found.

PMID- 26211120
TI  - Are You Hiring High Performers?

PMID- 26211121
TI  - Is Your Organization Providing True Equity of Care? Take a Hard Look Inside.

PMID- 26211122
TI  - CRISIS CONTROL. Stress training brings calm to hospitals' emergency departments.

PMID- 26211123
TI  - READY. SET. TEST. Survey: Providers readying for ICD-10; tests will tell just how
      ready they are.

PMID- 26211124
TI  - FILLING THE POOL. Health IT assistance found in their own backyards.

PMID- 26211125
TI  - SMOOTH TRANSITIONS. New hospital resources aim to improve discharge planning.

PMID- 26211126
TI  - MOST WIRED. Governance strategies can determine success of IT projects.

PMID- 26211127
TI  - A CLOSER READING. Diagnostic imaging under review.

PMID- 26211128
TI  - Can you imagine?

PMID- 26211129
TI  - Tech-friendly Spaces that Nurture.

PMID- 26211130
TI  - Who are the Disruptors?

PMID- 26211131
TI  - Partners in Population Health.

PMID- 26211132
TI  - Palmetto Health Wins Foster G. McGaw Prize.

PMID- 26211134
TI  - Snow Kept Falling Down, Hospital Staffs Kept Showing Up.

PMID- 26211133
TI  - Developing Physician Leaders.

PMID- 26211135
TI  - [Mothers empowered].

PMID- 26211136
TI  - [Prevention of vascular catheter associated sepsis: a new guideline from the USA
      practical recommendations].

PMID- 26211137
TI  - [Healthy start in life].

PMID- 26211138
TI  - [Implementation of development promoting care in neonatology from the viewpoint
      of organizational consulting. 1].

PMID- 26211139
TI  - [Letter on issue 11/14 introduction. "Social freezing"].

PMID- 26211140
TI  - [Family friendly versus staff shortage. "Career and family audit" certificate].

PMID- 26211141
TI  - [When children do not learn to speak].

PMID- 26211142
TI  - [Community work environment of family- health- and pediatric nurse].

PMID- 26211143
TI  - [Dt. Society of Social Pediatrics and Youth Medicine. Many chronically ill
      adolescents lose vital medical care access during transition to adulthood].

PMID- 26211144
TI  - [NEU: Topfer Midwives Colloquium].

PMID- 26211145
TI  - [Ill and disabled persons are entitled to proper documentation: efforts to reduce
      bureaucracy in nursing promise little success].

PMID- 26211146
TI  - [Interview about the book "preventing errors in pediatrics"].

PMID- 26211147
TI  - [Diagnosis and treatment of sleep disordered breathing: an update].
AB  - The sleep breathing disorders (SDB) include obstructive sleep apnea (OSA),
      central sleep apnea disorders, sleep related hypoventilation disorders, and sleep
      related hypoxemia disorder in international classification of sleep diseases 3rd
      edition (ICSD-3). Latest diagnosis criteria are introduced. Treatments, which
      target to Individual contributors, should be applied. Thus identification of the
      phenotype in patients with OSA is important. The methods of evaluation patients'
      arousal thresholds, loop gain as well as neuromyopathy in clinical setting are
      reported. Several new treatment strategies are developed and applied for OSA.
      Long term follow up and more data are needed for evaluation the outcomes of
      hypoglossal nerve stimulation, bariatric surgery as well as medicine as
      treatments for OSA.

PMID- 26211148
TI  - [Diagnosis and treatments of craniomaxillofacial deformities with OSDB].
AB  - Obstructive sleep disordered breathing (USDB) is a common diseases which caused
      by upper airway(UA) occlusion, muscle tone problems and collapse of upper airway
      etc. The article introduces how to select surgical treatment protocol. First, it
      is necessary of PSG and upper airway evaluation. Then, it is key to master
      surgical indications. For the children with hypertrophy of tonsillectomy or
      adenoidectomy, it may first step of tonsillectomy or adenoidectomy, they needed
      followed up by orthodontic doctor or orthognathic surgeon for tooth and
      maxillomandibular malformation. For the adult OSDB patients, there are two
      method, soft tissue reduction/mass excision around UA or maxillomandibular
      advancement(MMA), and MMA is recommended to the patients such as failure from
      UPPP and other surgical treatment, but for severe obesity patients, bariatric
      surgery is commended, it is very effective for soft tissue reduction around UA
      and weigh loss. For the OSDB patients with craniaomaxillomandibular deformities,
      such as craniosynostosis syndrome/micrognathia. Finally, it is important of the
      UA management for the surgical patients around perioperative period. All in all,
      it is necessary of the multidisciplinary cooperation for the OSDB patients,
      surgical treatment is useful method but it is not commend to all OSDB patients.

PMID- 26211149
TI  - [Application of noninvasive positive pressure ventilation for sleep disordered
      breathing in China].
AB  - After more than 30 years of development, noninvasive positive pressure
      ventilation (NPPV) has become one of the main treatments of sleep-disordered
      breathing (SDB) in the world. It is the wide application of this technology that
      makes breakthrough in SDB treatment, and has given rise to a new
      interdisciplinary area sleep medicine. In China, sleep medicine started in late
      of 1980's, in recent years, with the development of economy and the improvement
      of recognization, the application of NPPV in Chinese market has become one of the
      fastest growing in the world. NPPV technology also extends gradually to the
      treatments of patients with respiratory failure due to different causes, such as
      severe acute respiratory syndrome and COPD.

PMID- 26211150
TI  - [Redefine the efficacy of surgical treatments for obstructive sleep apnea
      hypopnea syndrome].
AB  - Various surgical procedures are widely used for treating obstructive sleep apnea
      hypopnea syndrome (OSAHS) currently. The most prominent advantage of surgery is
      the excellent long-term adherence, which is just the main limitation for the
      first-line treatment of continuous positive airway pressure (CPAP). However,
      nearly all the surgical procedures used now usually could not cure this disease
      completely. The success rate of the uvulopalatopharyngoplasty, which is the most
      widely used procedure, can only reach to 40% - 50% in terms of AHI Therefore,
      there are some opinions that the surgery should not be applied for treating this
      disease. In fact, the outcomes of surgical treatments should not be only
      evaluated basing on some of the objective results. In this article, the clinical
      significance of surgery based on objective and subjective data, and the effects
      on long-term consequences, the combination of surgery with CPAP, and the possible
      prospects of surgical treatments for this disease will be discussed. This may
      help us to redefine the clinical efficacy of surgery for the treatment of OSAHS.

PMID- 26211151
TI  - [Improving the surgical technology in treatment of OSAHS].
AB  - Noninvasive continuous positive airway pressure (CPAP) for the ventilation
      treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS) is the first-line
      treatment method. This article aims to describe the effect of surgical operation
      especially for the UPPP in the individualized comprehensive treatment of OSAHS
      and the importance of surgical technique. Lower compliance is the bottleneck of
      CPAP therapy in clinical application, for the OSAHS patients with treatment
      failure in CPAP or those cannot accept CPAP therapy, when with no other ideal
      instrument therapeutics, accurate diagnosis of position in airway obstruction
      with an adequate surgical operation is the treatment,of choice. Surgical
      operation is particularly important either as a fore-lying means to improve the
      CPAP treatment compliance or as an independence treatment method of OSAHS. The
      pharyngeal cavity is the most common obstructive plane in patients with OSAHS.
      The operation of traditional UPPP aiming at the expansion of pharyngeal cavity is
      the classics surgery to solve obstruction in this plane, the lower operation
      effective rate is the main reason of restriction in its development. How to
      improve the effective rate of surgical treatment of OSAHS is our surgical goal.
      The effective rate of surgical operation treatment in OSAHS rely on the following
      sides: to follow the OSAHS individualized comprehensive treatment principle,
      reasonable choice of surgical operation indication, the precise localization
      diagnosis of upper airway obstruction, adequate surgical operation and skilled
      surgical techniques.

PMID- 26211152
TI  - [Meta analysis of nasal surgery alone for obstructive sleep apnea hypopnea
      syndrome].
AB  - OBJECTIVE: To investigate the effect of nasal surgery alone for OSAHS using Meta
      analysis. METHOD: The published articles were searched from PubMed, Chinese
      Biomedical Literature CD-ROM databases, China Academic Journals Full-text
      database. The quality of the searched original studies were assessed and the
      outcomes with the requirements were analyzed. RESULT: Nineteen articles and 621
      cases were finally included, including 15 English literatures and 4 Chinese
      literatures. The results of Meta analysis showed that: (1)The weighted mean
      between pre-and postoperative AHI was no significantly difference [weighted mean
      difference (WMD) = 0. 11, 95% CI (-0. 02,0. 23), P>0. 05]. (2) The nasal surgery
      alone significantly reduced theEpworth sleepiness scale scores in thirteen
      studies [WMD=0. 94,95% CI (0. 62,1. 26), P<. 01]. CONCLUSION: The meta-analyses
      show that nasal surgery alone can effectively improve the subjective clinical
      symptoms of patients with OSAHS. However, nasal surgery alone has a limited
      efficacy in treating OSAHS.

PMID- 26211153
TI  - [The clinical effect observation for surgery of nose and pharyngeal auxiliary
      oral appliance in severe OSAHS].
AB  - OBJECTIVE: To investigate the therapeutic effects of oral modified device
      combined with nasopharyngeal enlargement surgery and evaluate the oral modified
      device' s adjuvant therapy meaning in severe OSAHS patients after surgery
      treatment. METHOD: 46 cases with severe OSAHS were diagnosed by PSG according to
      AHI and the lowest arterial oxygen saturation (LSaO2). We performed the nasal or
      pharyngeal cavity expansion surgery for them according to the pathological change
      part correspondingly. Then all subjects were divided into combined group (n=26)
      and surgery alone group (n=20) according to their personal willingness. We
      monitored the PSG for all subjects aftter 2 weeks and 3 months respectively, then
      we calculate the diversity between the two group or intragroup change on the
      basis of the AHI, LAT, LSaO2, mean arterial oxygen saturation (MSaO2) and sleep
      structures recorded by PSG. At the same time, we collected the subjective
      sensations by questionnaire. RESULT: The AHI and LAT in combined group were
      significantly lower and LSaO2 was significantly higher than these in surgery
      alone group(P<0. 05), and it's no difference in MSO2 between the two groups (P>0.
      05). The N 1% was more shorter and the N2% and N3% were more longer after nasal
      or pharyngeal operation compared with pre-operative states in both groups(P<.
      05), but we didn't find difference in REM%(P>. 05). The data of PSG also showed
      that the shallow sleep proportion was more shorter and the slow wave sleep
      proportion was more longer in combined group compared with surgery alone group.
      The subjective sensations results also showed significantly alleviated in
      combined group, such as mental state, daytime sleepiness and physical strength.
      The efficiency ratio of treatment was 85. 0% and 92. 3% in surgery alone group
      and combined group respectively. CONCLUSION: Nasal and pharyngeal cavity
      enlargement surgery combined with oral modified device is a more effective
      treatment in patients with severe OSAHS, and it is meaningful for the long-term
      curative effect of surgery to prevent relapse and improve.

PMID- 26211154
TI  - [Effect of continuous positive airway pressure ventilation on serum levels of
      s100beta protein and neuron-specifice enolase in obstructive sleep apnea-hypopnea
      syndrome patients].
AB  - OBJECTIVE: To explore the effect and clinical significance of serum S100beta and
      NSE on moderate and severe obstructive sleep apnea syndrome (OSAHS) after the
      continuous positive airway pressure (CPAP). METHOD: A total of 60 cases with
      obstructive sleep apnea were choosed with PSG in our hospital in June 2009 to
      June 2009. According to apnea hypoventilation index and at night the lowest
      oxygen saturation, divided into severe group (n=60) and moderate group (n=60),
      selecting 60 cases of healthy physical examination for a control over the same
      period. According to the length of the course of the disease in patients with
      each group can be divided into <5 years group, 5-10 years and > 10 years group,
      severe and moderate groups were recruited to undergo an CPAP treatment,both
      before and after treatment for 3 months, the lowest oxygen saturation, average
      blood oxygen saturation and apnea hypoventilation index were determined in
      moderate and severe groups with PSG, at the same time, serum S100beta and NSE
      were determined with immune enzyme-linked adsorption testing before and after
      patients in different course of treatment and control group. RESULT: Compared
      with pretherapy of severe and moderate groups, the lowest oxygen saturation,
      average blood oxygen saturation and apnea hypoventilation index were ower after
      treatment (P<0. 05), serum S100beta and NSE in severe and moderate groups before
      and after treatment were significantly higher than control group (P<0. 05), and
      two groups > 10 years before and after treatment in patients with serum according
      to beta and NSE levels higher than 5-10 patients, 5-10 patients before and after
      treatment according to beta and NSE serum levels higher than <5 years group of
      patients, the relation between the two groups of patients before and after
      treatment according to beta and NSE serum levels with the extension of history
      time increased. Before the treatment serum according to beta and NSE in patients
      with severe group were higher than moderate group before treatment (P< 0.05).
      Relation between the two groups after treatment according to beta and serum NSE
      was significantly decreased the (P<0. 05), the relation between the two groups
      after treatment according to beta and serum NSE, there was no statistically
      significant difference (p>0. 05), the relation between two groups according to
      beta, NSE serum are positively correlated with AHI (P < 0. 01). CONCLUTION: CPAP
      significantly reduced serum S100beta and NSE levels in patients with OSAHS, both
      may be important index which evaluated nervous system protection of CPAP in
      patients with OSAHS.

PMID- 26211155
TI  - [The management of laryngotracheal defect derived from thyroid gland papillary
      carcinoma resection].
AB  - OBJECTIVE: To investigate the preservation of the structure and function of the
      trachea and larynx, the management of laryngotracheal defect when trachea and
      larynx was involved. METHOD: To review the management and clinical results of 13
      cases of thyroid papillary carcinoma with larynx and trachea involvement, the
      preservation of laryngotracheal structure and relative defect reconstruction of
      our department from 2007-2014. Those patients being performed total laryngectomy
      was excluded. 3 males and 10 females, aged from 46 to 67 years old with median
      age of 53 were included. Among them 8 cases were recurrent. The extent of the
      tumor foci was estimated with the help of computed tomography and
      laryngofiberoscope before surgery. Selective neck dissection, total thyroidectomy
      and related laryngotracheal resection was performed for the first time operation
      patient, while selective neck dissection, recurrent foci and related larynx and
      trachea resection was performed for those recurrent patients. Three kinds of
      modalities were applied to manage the laryngotracheal defect including to
      reconstruct with pedicled sternocleidomastoid clavicular periosteocutaneous flap,
      pedicled trapizius muscular flap and to preserve the remaining larynx and trachea
      and perform a stoma of larynx and trachea which repaired by a second-stage
      procedure. The patients were followed-up from half an year to 3 years. RESULT:
      Ten patients out of 13 decannulated while another 3 cases, 2 of which were
      performed local flap to reduce the stoma, wore tracheal tubes all time.
      CONCLUSION: Either flap transfer or laryngotracheal stoma before second stage
      repair might preserve partial laryngotacheal anatomy and function in selected
      cases thus improve the life quality of the patients.

PMID- 26211156
TI  - [Analysis the relationship of mean platelet volume and obstructive sleep apnea
      and hypopnea syndrome].
AB  - OBJECTIVE: Uur aim was to investigate the association between OSAHS and mean
      platelet volume (MPV) value. METHOD: This study included 70 cases with OSAHS in
      our ward between Jan. 2012 and Jan. 2014, and the OSAHS patients were divided two
      groups: mild- to moderate group and severe group; 30 age-and sex-matched healthy
      subjects was in control group. The correlation among the levels of the number of
      platelets (PLT), MPV, platelet distribution width (PDW) were evaluated in the two
      groups. RESULT: PLT count was significantly lower in the severe group than the
      control group [(202. 8 +/- 68. 9] * 10(9)/L, (235. 9 +/- 65. 2) * 10(9)/L]; MPV
      and PDW were significantly higher in the severe group [(10. 9 +/- 0. 9), (10. 4+/
      0. 8) fL; (12. 9 +/- 1. 9) %, (12. 0 +/- 1. 4) %]. There was not significantly
      difference of MPV between the mild to moderate group and the control group [(10.
      7 +/- 0. 7), (10. 4 +/- 0. 8)fL]. CONCLUSION: MPV levels are elevated in patients
      with the severe OSAHS.

PMID- 26211157
TI  - [The characteristics of polysomnographic values and synchronous blood pressure in
      patients of obstructive sleep apnea with hypertension].
AB  - OBJECTIVE: To analyze the differences of sleep respiratory parameters recorded by
      PSG and synchronous blood pressure measured by ambulatory blood pressure monitor
      between obstructive sleep apnea (OSA) patients with hypertension (HT) and simple
      OSA and simple HT; To determine the characteristics of sleep respiratory
      parameters and blood pressure changes in patient with OSA accompanied HT. METHOD:
      We chose the patients who were diagnosed simple HT (n=45) and simple OSA (n=50)
      and OSA with HT (n=56), Compared the sleep respiratory parameters and blood
      pressure changes between the three groups. Meanwhile the correlations about the
      sleep respiratory parameters and synchronization blood pressure were analyzed.
      RESULT: Compared with simple HT and simple OSA, OSA with HT has higher apnea
      hyponea Index (AHI) (P<0. 001), oxygen desaturation index (ODI), awake index
      (AI), wake after sleep onset (WASO) and the proportion of non-rapid eyemovement
      sleepl (N1) in total sleep time(TST), has lower mean arterial oxygen saturation
      (MSaO2), lowest arterial saturation oxygen (LSaO2), the proportion of slow wave
      sleep (SWS) and rapid eyemovement sleep (REM) in TST (P<0. 05). There were
      positive correlations between the systolic/diastolic blood pressure (SBP/ DBP)
      and AHI, ODI, AI, WASO and N1/TST (P<0. 05). Compared with simple OSA, the mean
      day systolic blood pressure (dMSP), mean night systolic blood pressure (nMSP),
      mean day diastolic blood pressure (dMDP), mean night diastolic blood pressure
      (nMDP) and mean night diastolic blood pressure (nMDP) were significantly decre-
      sed, meanwhile the difference between the average systolic/diastolic blood
      pressure day and night were significantly increased after continuous positive
      airway pressure (CPAP) treatment. OSA with HT has higher There were negative
      correlations between the SBP/DBP and MSaO2, LSaO2 (P<0. 05). Blood pressure
      mainly changed in the later sleep stage when the REM phase was increased. Blood
      pressure changes were characteristic of increasing DBP and decreasing SaO2.
      CONCLUSION: There are significant differences between simple OSA and OSA with HT
      in the sleep respiratory parameters, which are closely related with changes of
      blood pressure in sleep stage; AHI is the high risk factor of the OSA with HT.
      PSG is a effective factor in estimating the OSA accompanied HT course of
      development and prognosis.

PMID- 26211158
TI  - [Observation of nasal obstruction symptom evaluation questionnaire and Epworth
      sleep score in nasal cavity ventilation expansion techniques for patients with
      obstructive sleep apnea hypopnea].
AB  - OBJECTIVE: To realize the application of nasal obstruction symptom evaluation
      (NOSE) and Epworth sleep score (ESS) before and after nasal cavity ventilation
      expansion techniques. METHOD: Forty-two OSAHS patients with nasal obstructive
      symptoms were diagnosed by clinical symptoms and polysomnography. Nasal cavity
      ventilation expansion technique was performed. Before and after the surgery, the
      NOSE and ESS were used to compare the difference. Postoperative data were
      obtained at least 3 months later. RESULT: Compared the data before and after
      operation, the NOSE and ESS were significantly decreased respectively (P<0. 05),
      there is no significant difference between 3 groups (P>0. 05). CONCLUSION: The
      result suggest that OSAHS patients taking nasal cavity ventilation expansion
      operations showed improvement in severity of nasal obstructive symptoms and daily
      sleepy.

PMID- 26211159
TI  - [Analysis of the causes of postoperative delayed hemorrhage of low temperature
      plasma tonsillectomy in children].
AB  - OBJECTIVE: Probe into the causes of postoperative delayed hemorrhage of low
      temperature plasma tonsillectomy in children. METHOD: The methods of
      retrospective analysis the difference of postoperative bleeding time and bleeding
      rate between tonsillectomy by the low temperature plasma and the traditional cold
      surgical devices in 2-14 years old children. Plasma group contained the
      tonsillectomy by low temperature plasma between the March in 2012 to the August
      in 2013. Traditional group contained the tonsillectomy by traditional cold
      surgical devices between the March in 2005 to the August in 2006. RESULT: In the
      1,000 cases of plasma group, 19 cases occurred postoperative hemorrhage, the
      hemorrhage rate was 1. 9%. Four cases occurred postoperative primary hemorrhage
      in 8 hours after operation, the postoperative primary hemorrhage rate was 0. 4%.
      Fifteen cases occurred postoperative delayed hemorrhage, the delayed hemorrhage
      rate was 1. 50%, the bleeding time was 2-13 days after operation, the average
      number was 7. 5 days. Nine cases had wound infection and 6 cases had eaten some
      food improperly in these 15 cases. And in these eaten improperly cases, 4
      children had eaten fruit and hard food, 2 children had eaten a little food who
      lost their weight. In 860 cases of the traditional group, 29 cases occurred
      postoperative hemorrhage, the hemorrhage rate was 3. 37%. 26 cases occurred
      postoperative primary hemorrhage in 8 hours after operation, the postoperative
      primary hemorrhage rate was 3. 02%. Three cases occurred postoperative delayed
      hemorrhage, the delayed hemorrhage rate was 0. 35%, the bleeding time was 2-6
      days, the average number was 4 days. CONCLUSION: It is preferable for chileren to
      having low temperature plasma tonsillectomy. The causes of postoperative delayed
      hemorrhage of low temperature plasma tonsillectomy in children are probably
      related to the postoperative infection, the differences of operation skills, the
      method of stop bleeding, eating the wrong foods, irritating cough, improper
      nursing and so on.

PMID- 26211160
TI  - [The feasibility study of prediction internal carotid artery whether can
      resection by monitoring carotid artery pressure preoperative].
AB  - OBJECTIVE: Through preoperative temporary balloon occlusion of internal carotid
      artery and monitoring of carotid artery stump pressure variation, in order to
      further predict the risk of carotid artery ligation and resection, evaluation
      operative risk and provides the reference for the choice of surgical approach.
      METHOD: Continuous monitoring and recording the carotid artery stump return
      pressure,before clamping and in the process of blocking, close observation the
      patients mental state and the nervous systemof all kinds of signs, in the process
      of blocking, to understand the dynamic change of stump artery pressure return in
      patients and whether can the smooth passage of carotid artery balloon occlusion
      test. RESULT: Of the 19 patients, 4 cases were positive, 15 negative cases,
      Blocking immediate the positive patients and negative patients with stump
      pressure drop was (57. 35 +/- 1. 89) % and (38. 99 +/- 12. 23) %, with
      statistical significance between the two, in the process of blocking, the mean
      stump pressure of the positive patients and the negative patients was (37. 29 +/-
      3. 15) mmHg and (61. 36 +/- 14. 69) mmHg, with statistical significance between
      the two. CONCLUSION: Approximately 21. 05% of patients can not tolerate carotid
      artery balloon occlusion test, theory for carotid artery reconstruction
      operation. After blocking the stump pressure is less than 40. 44 mmHg, the theory
      for reconstruction of the internal carotid artery operation. Blocking instant
      artery stump pressure dropped more than 55. 46%, in theory the need for internal
      carotid artery reconstruction.

PMID- 26211161
TI  - [Clinical observation of early enteral nutrition support for post-laryngectomy
      patients].
AB  - OBJECTIVE: To compare the postoperative nutritional status and the incidence of
      postoperative infection between post-laryngectomy patients with early eternal
      nutrition and those with normal liquid diet. METHOD: The observational group were
      given eternal nutrition while the control group were given normal liquid diet.
      Nutrition indicators (total protein, albumin, globulin, prealbumin, hemoglobin,
      body weight) and immune parameters (lymphocyte count) were measured at
      preoperative day 3 and postoperative day 3, 7 and 10. The incidence of
      complications and postoperative hospitalization days were compared and analyzed.
      RESULT: Compared with the control group, the total protein, albumin and globulin
      of observational group had no statistic significance at postoperative day 3, the
      total protein, albumin,globulin of observational group were higher (P<0. 05) at
      postoperative day 7 and 10: The body weight had no satisic significance at
      postoperative day 3 and 7, while observation group higher at postoperative day
      10, while the hemoglobin of observational group had no statistic significance:
      The prealbumin and lymphocyte count had no statistic significance. The
      postoperative hospitalization days of the observational group was lower (P<0. 05)
      than the control group. CONCLUSION: The early eternal nutrition for post
      laryngectomy patients are conducive to improve of nutritional status and reduce
      the rate of post-operative complications.

PMID- 26211162
TI  - [Clinical significance of ultrasonography in the diagnosis of central clearing of
      papillary thyroid carcinoma].
AB  - OBJECTIVE: The purpose of this article is to discuss the clinical value of
      central neck lymph node dissection in papillary thyroid carcinoma, especially in
      thyroid papillary microcarcinoma (PTMC). Also this article wants to evaluate the
      diagnostic significance of preoperative ultrasonography of central neck
      metastasis lymph nodes and the clinical significance of preoperative
      ultrasonography in central neck lymph node dissection. METHOD: Collected and
      analyzed 121 cases from September 2012 to December 2013. All of them had done the
      central neck lymph node dissection with the same standard by the same surgeon in
      our department. Evaluate the value of preoperative ultrasound diagnostic in
      thyroid microcarcinoma and non-microcarcinoma. RESULT: In the 121 patients, The
      62 patients were diagnosed with PTMC (primary lesion d<=1. 0 cm). Accuracy rate
      of ultrasound diagnostic was 74. 2% (46/62), the rate of missed diagnosis was 61.
      9% (13/21), the rate of misdiagnosis was 7. 3 % (3/41), sensitivity was 38. 1%
      (8/21), specificity was 92.7% (38/41), positive predictive value was 72. 7%
      (8/11), negative predictive value was 74. 5% (38/51) and the value of Kappa was
      0. 3485. The other 59 patients was diagnosed with thyroid papillary non
      microcarcinoma (primary lesion d>1. 0 cm). The accuracy rate was 55. 9% (33/ 59),
      the rate of missed diagnosis was 58. 3% (21/36), the rate of misdiagnosis was 21.
      7% (5/23), sensitivity was 41. 7% (15/36), specificity was 78. 3% (18/23),
      positive predictive value was 75. 0% (15/20), negative predictive value was 46.
      2% (18/39) and the value of Kappa was 0. 1757. CONCLUSION: Cervical central lymph
      node dissection was necessary when the ultrasound diagnosis of cervical central
      lymph node-positive was prompted suspiciously in the thyroid papillary
      microcarcinoma. However, when it prompted negative, we could recommend patients
      to do the prophylactic central lymph node dissection in conjunction with the risk
      factors. Whether the ultrasound diagnosis of central lymph node was prompted
      suspiciously or not in the thyroid papillary microcarcinoma and non
      microcarcinoma, the central lymph nodes dissection is necessary.

PMID- 26211163
TI  - [Clinical characteristics of 97 hypopharyngeal carcinoma cases].
AB  - OBJECTIVE: Study the clinical characteristics, treatment results and prognostic
      factors of hypopharyngeal carcinoma. MMETHOD: A retrospective analysis was
      performed of 97 hypopharyngeal cases that were treated in Department of
      Dtolaryngology of our hospital from January 2008 to December 2012. 93 cases of
      them are male patients, and 4 cases are female patients. The tumors are
      originated from pyriform sinus(75 cases), posterior pharyngeal wall (16 cases)
      and post-cricoid area (6 cases). Of the 97 patients,21 patients were treated with
      partial hypopharynx resection (21. 6%), 7 were treated with partial laryngectomy+
      partial hypopharynx resection (7. 2%), 53 were treated with total
      laryngectomy+partial hypopharynx resection (54. 6%), 12 were treated with total
      laryngectomy and total hypopharynx resection, gastric-pharyngeal anastomosis (12.
      4%) and 4 were treated with total laryngectomy and total hypopharynx resection,
      enteric-pharyngeal anastomosis (4. 1%). Sixty-one cases undergo postoperative
      radiotherapy in Oncology. Use Chi-square test to do enumeration data analysis,
      the survival rate is calculated with the life table method, survival analysis
      with Kaplan-Meier method, parallel Log-rank test. Cox regression multivariate
      analysis model is used to find the factors affecting prognosis. RESULT: The
      follow-up rate of this group was 90. 7%. All patients' 1-year survival rate is
      76. 0% , 3-year survival rate is 56. 0%, pathological lymph node metastasis rate
      is 71. 1%, occult lymph node metastasis rate is 19. 6%. Local recurrence rate is
      21. 6%. The main reasons of death in patients include : cervical lymph node
      metastasis in 7 patients (21. 9%), local recurrence in 12 cases (37. 5%), distant
      metastases in 10 patients (31. 3%) and so on. Univariate analysis showed that
      tumor size (P<0. 01) and tumor T stage (P<0. 05) have impact on survival
      prognosis, no risk factors was found with Cox regression multivariate analysis.
      CONCLUSION: Hypopharyngeal carcinoma is difficult to be found early, prone to
      recurrence and metastasis after operation, carefully chosen surgical excision and
      neck dissection, adjuvant postoperative radiation therapy is the main treatment
      strategy. Posterior pharyngeal wall carcinoma tend to have higer recurrence and
      metastasis rate than the other two types of hypopharyngeal caocinom, and
      treatment would cause much larger injury, so more attention should be paid to
      this type of hypopharyngeal caocinom.

PMID- 26211164
TI  - [The influence of autophagy-related genes about X-Ray on nasopharyngeal carcinoma
      CNE2 and CNE2/DDP cells].
AB  - OBJECTIVE: To study the relationship between the radiotherapy resistance and
      autophagy. To provide a theoretiacal basis for drugs that regulate autophagy to
      improve radiotherapy sensitivity. METHOD: Flow cytometry (FCM) was performed to
      analyze the distribution of the cell cycle of CNE2 and CNE2/DDP cells under the
      action of X radiation. The expression of autopagy-specific gene Beclin1 and
      microtubule-associated protein light chain 3beta (MAPLC3beta) in CNE2 and
      CNE2/DDP cells was determined by real time PCR and Immumofluorescence staining.
      RESULT: CNE2/DDP and their parental CNE2 cells produced the G2-M phase arrest
      under the action of X radiation. With the radiation dose increasing,The cells
      which in the G2-M phase were more and more (P<0. 05). The G2-M phase arrest in
      CNE2/DDP cells was more obvious than in CNE2 cells (P<0. 05). The expression of
      Beclin1 and MAPLC3beta in CNE2 and CNE2/DDP cells increased under the action of X
      radiation. What's more, the raise was more and more obvious with the increase of
      the irradiation dose(P<0. 05). The expression levels of Beclin1 and MAPLC3beta in
      CNE2/DDP was lower than that in CNE2 cells (P<0. 05). CONCLUSION: Autophagic cell
      death may be the one manner of death in nasopharyngeal carcinoma CNE2 and
      CNE2/DDP cells under the action of X radiation. The radiation resistance of
      CNE2/DDP cells may be related to the low expression of autophagy-related genes.

PMID- 26211165
TI  - [Tumor suppressive effect and relative mechanisms of tea polyphenol on
      nasopharyngeal carcinoma cells].
AB  - OBJECTIVE: To investigate the effect and mechanism of tea polyphenol (TP) on the
      proliferation, apoptosis, migration and invasion of nasopharyngeal carcinoma(NPC)
      cell line HONEl. METHOD: After treated with different concentration of tea
      polyphenol, CCK-8 assay, fluorescent staining, cell scratching assay and
      transwell assay were applied to detect the effect of tea polyphenol on the HONE1
      cells. Furthermore, the expression of protein VEGF was investigated by flow
      cytometry assay. RESULT: It was found that tea polyphenol could inhibit NPC cell
      proliferation significantly in a dose-dependent manner, however, little impact
      was observed in normal nasopharyngeal epithelial cell line NP69. Furthermore, it
      was demonstrated by fluorescent staining assay that tea polyphenol could induce
      NPC cell apoptosis, and cell scratching assay and transwell assay showed that tea
      polyphenol could inhibit cell migration and invasion. CONCLUSION: Tea polyphenol
      can significantly inhibit cell proliferation, induce cell apoptosis and decreased
      the migration and invasion ability of NPC cells in vitro. Tea polyphenol might be
      a tumor suppressor of NPC cells.

PMID- 26211166
TI  - [Clinical application of radiofrequency ablation combined with nasal endoscopy in
      the treatment of pedunculated hemangioma in pharyngeal and laryngeal].

PMID- 26211167
TI  - [The use of the catheter laryngeal keel in anterior glottic webs].

PMID- 26211168
TI  - [The evaluation of the application effect about resection of tongue cyst by Low
      temperature plasma radiofrequency ablation system].

PMID- 26211169
TI  - [Experience of 22 patients with inhalation injury].

PMID- 26211170
TI  - [Bilateral papillary thyroid carcinoma concurrent with parathyroid adenoma: one
      case report].
AB  - Concurrent thyroid carcinoma and parathyroid adenoma is rare, they can and do
      coexist. We present here a 63-year old man who had bilateral papillary thyroid
      carcinoma and a parathyroid adenoma in the right thyroid lobe. Thyroid cancer was
      confirmed surgically. After the operation, the patient was found hypercalcemie
      and hypophosphatemia along with an elevated parathyroid hormone (PTH), indicating
      primary hyperparathyroidism. Also, the parathyroid 99mTc-MIBI scan demonstrated
      parathyroid adenoma in the right lower pole of the thyroid. The abnormal
      parathyroid tissue was carried out, and then serum calcium and PTH levels
      decreased to normal ranges.

PMID- 26211171
TI  - [One case of esophageal carcinoma defect after operation for repair with platysma
      myocutaneous flap].
AB  - Cervical esophageal carcinoma is rare, the lack of early clinical manifestations,
      early diagnosis is difficult, easily missed or misdiagnosed, especially at
      present for the method of repairing defect of cervical esophagus cancer after
      operation. In many mainstream, the repair methods with free jejunum, gastric pull
      up, and anterolateral thigh flap freeforearm flap. We used the platysma skin flap
      to repair of cervical esophagus defect which is worthy of reference,report as
      follows now.

PMID- 26211172
TI  - [A case of huge malignant maxillofacial tumor].
AB  - Patients found two years left of the new biology, surface erosion,exudates long.
      Postoperative pathology examination: inflammatory fibrous background visible
      uniform small cells arranged in cords, pseudorosette formation region is
      considered not except basal cell carcinoma , neuroendodrne carcinoma. Diagnosis
      of immunohistochemical support of basal cell carcinonma.

PMID- 26211173
TI  - [A case report of metal penetrating trauma in maxillo-facial, neck and chest].
AB  - A 21 years old male patient was admitted with a complex trauma of metal
      penetrating wound in maxillo facial region,neck and chest because of a high
      falling accident one hour ago. General examination:the vital signs were stable.
      Specialized examination: metal foreign body penetrated from the front wall of the
      axilla ,passing left clavicle superficies, through the middle of neck into the
      posterior pharyngeal wall, then piercing out from the superciliary arch lateral.
      The patient had apparent tenderness in the right arch,right zygomatic bone and
      the front of right maxilla. the degree of mouth was about 1. 8cm. X-ray showed
      the foreign body: from left armpit to right temporal part. The admission
      diagnosis was : 1. metal penetrating wound in maxillo-facial,neck and chest; 2.
      right zygomatic maxillary and zygomatic arch fractures. Treatment: the foreign
      body was removed smoothly through the concurrent operation, and by scendary
      operation of open reduction and internal fixation of fractures, the finally
      result of patient was good.

PMID- 26211174
TI  - [DNA methylation in thyroid carcinoma].
AB  - Cancer has become clear that not merely gene variations but also epigenetic
      modifications may contribute to it. Epigenetic changes refer to stable
      alterations in gene expression with unrelated to changes in the underlying
      genetic sequence,resulting in heritable. DNA methylation is one of the common
      epigenetic changes. It control the gene expression through changing DNA
      conformation and stability, chromatin structer, DNA-protein interaction. The
      reversal of dysregulated DNA methylation has emerged as a potential strategy for
      the treatment of thyroid carcinoma. The artical will provide an overview of how
      DNA methylation contribute to thyroid carcinoma dissemination,invasion and
      metastasis and we will summarize the latest epigenetic therapies for thyroid
      carcinoma.

PMID- 26211175
TI  - [The progress of radiofrequency ablation technique in the early glottic cancer].
AB  - In recent years, radiofrequency ablation technique is widely used in
      Otolaryngology Head and Neck Surgery clinical work, domestic scholars preliminary
      study the efficacy to early glottic cancer. The review will discuss the
      definition and the main treatment strategy of early glottic cancer, theory and
      history of radiofrequency ablation technique, vocal endoscopic surgical
      procedures and safety margin, Clinical observation of radiofrequency ablation
      technique to treat early glottic cancer.

PMID- 26211176
TI  - [Correction of hypotelorism in craniofacial deformity].
AB  - OBJECTIVE: To investigate the diagnosis and treatment of hypotelorism. METHODS:
      From Jan. 2000 to Jan. 2014, 6 cases with hypotelorism were retrospectively
      studied. Among them, 3 cases had craniosynostosis, 2 had holoprosencephaly, and 1
      had cleft lip. All the cases were diagnosed and treated by bone graft or spring
      distraction to correct the hypotelorism. RESULTS: 2 cases were treated by none
      graft and 4 cases were treated by external spring distraction. All the patients
      completed the treatment successfully with obvious improvement in appearance. No
      complication happened. 4 cases were followed up for 2 years with an average
      fronto-orbital axis angle as (50 +/- 8)  degrees . CONCLUSIONS: Hypotelorism can
      be successfully corrected by bone graft as fronto-orbital bridge or spring
      distraction.

PMID- 26211177
TI  - [Vascularized composite flap with iliac crest and internal oblique muscle of
      abdomen for half mandibular reconstruction].
AB  - OBJECTIVE: To investigate the effect of vascularized composite flap with iliac
      crest and nternal oblique muscle of abdomen for half mandibular reconstruction.
      METHODS: From July 2009 to Sept. 2013, 14 cases with half mandibular defect after
      tumor resection were treated with composite flap of iliac crest and internal
      oblique muscle of abdomen pedicled by deep circumflex iliac vessels. During
      operation, one group performed tumor resection and got the recipient area vessels
      ready for anastomosis. The other group performed harvesting of composite flap.
      Then the flap was trimmed and fixed to construct the defect with vessel
      anastomosis. RESULTS: All the 14 composite flaps survived with local infection
      only in 1 case. The size of harvested iliac crest ranged from 6 cm x 3 cm to 9 cm
      x 3 cm. The size of harvested internal oblique muscle of abdomen ranged from 5 cm
      x 4 cm to 7 cm x 5 cm. The patients were followed up for 6 months to 26 months
      (mean, 13 months) with satisfactory results and no complication. Mandibular
      panoramic radiographs showed new bone formation and good union. CONCLUSIONS:
      Vascularized composite flap with iliac crest and internal oblique muscle of
      abdomen has the advantages of abundant bone volume, as well as soft tissue
      reconstruction in one stage. The reconstructed mandible can attain normal
      function and appearance.

PMID- 26211178
TI  - [The application of facial liposuction and fat grafting in the remodeling of
      facial contour].
AB  - OBJECTIVE: To investigate the application of facial liposuction and fat grafting
      in the remodeling of facial contour. METHODS: From Nov. 2008 to Mar. 2014, 49
      cases received facial liposuction and fat grafting to improve facial contours.
      Subcutaneous facial liposuction with tumescent technique and chin fat grafting
      were performed in all the cases, buccal fat pad excision of fat in 7 cases, the
      masseter injection of botulinum toxin type A in 9 cases, temporal fat grafting in
      25 cases, forehead fat grafting in 15 cases. RESULTS: Marked improvement was
      achieved in all the patients with stable results during the follow-up period of 6
      - 24 months. Complications, such as asymmetric, unsmooth and sagging were
      retreated with acceptance results. CONCLUSION: Combination application of
      liposuction and fat grafting can effectively and easily improve the facial
      contour with low risk.

PMID- 26211179
TI  - [Application of intense pulsed light depilation in the auricular reconstruction
      with totally expanded skin].
AB  - OBJECTIVE: To investigate the application of intense pulsed light (IPL)
      depilation in the auricular reconstruction with totally expanded skin and its
      suitable parameter. METHODS: From February 2009 to September 2013, one tissue
      expander(100 or 150 milliliters) were implanted under the skin of mastoid in 126
      patients who suffered from microtia. During the skin expanding, the hair on the
      expanded skin was depilated by JPL technique. The parameter, operation, interval,
      the depilation result and the complication were recorded. The autologous rib
      cartilage frameworks were implanted in the second phase of auricular
      reconstruction. RESULTS: The energy of IPL was 20 - 35 J/cm2 (mean 25. 3 J/cm2),
      the width of pulse was 26 - 30 ms ( mean 27. 9 ms), the interval between two
      operations was 4 weeks. Ninety-six patients were cured(76. 2%, 96/126). The total
      depilation efficient is 96. 8% (122/126). A fine banding blisters was found in
      one patient whose depilation areas was marked by black pen. Skin erythema was
      found in five patients and skin pigmentation was found in 7 patients. There were
      no skin necrosis and expander exposure in all patients. During 6 - 12 months of
      follow-up period, ninety-two patients were cured (73.0%, 92/126) and the total
      depilation efficient is 92. 9% (117/126). CONCLUSIONS: IPL depilation during the
      skin expanding is feasible and safe with careful procedure. The hairless expanded
      skin is enough to cover the framework, as well as the post-auricular area. The
      appearance of reconstructed ear is better without hair.

PMID- 26211180
TI  - [Surgical treatment of eyelid divided nevus].
AB  - OBJECTIVE: To investigate the surgical techniques and therapeutic effect of
      eyelid divided nevus. METHODS: From January 2000 to January 2014, 27 cases with
      27 eyelid divided nevi were treated by staged excision (2 cases), or full
      thickness skin graft (20 cases) or frontal and facial expanded flaps (3 cases),
      or combined expanded flaps with skin grafts (2 cases) for large lesions. One case
      with skin graft underwent secondary treatment with expanded flap due to obvious
      scar. RESULTS: Except for one case with residue lesion (0. 5 cm x 0. 5 cm), all
      the other cases underwent successful treatment with primary healing. All the
      patients were followed up for 3-48 months (average, 7. 4 months). Except for one
      case with secondary expanded flap treatment, all the other patients were
      satisfied with aesthetic and functional results. No occurrence happened.
      CONCLUSIONS: Staged excision and full-thickness skin grafts are simple and
      effective method for eyelid divided nevus. For large lesions, expanded flap, or
      combined with skin graft should be considered.

PMID- 26211181
TI  - [Correction of upper eyelid depression by transposition of orbital septum fat].
AB  - OBJECTIVE: To discuss the operation method and characteristic of correcting upper
      eyelid depression by transposition of orbital septum fat. METHODS: During the
      double eyelid surgery, we set.the lateral orbital septum fat completely free,
      while the bottom is still connected with the middle orbital septum fat. We
      separate a tunnel from the middle to the inner side in orbital septum, and the
      separated orbital septum fat is transposed to the inner side of orbital septum by
      the tunnel with suturing fixation. RESULTS: From March 2008 to October 2013, 51
      cases with upper eyelid depression were treated successfully. Patients were
      followed up for 3 months to 3 years (average, 7. 5 months) with sustained
      aesthetic results. CONCLUSIONS: Orbital septum fat transposition can successfully
      correct the upper eyelid depression. It should become a regular procedure in
      blepharoplasty.

PMID- 26211182
TI  - [Analysis of the difference between the appearance and the bony structure in the
      polysyndactyly of the fifth toe fused with the fourth toe].
AB  - OBJECTIVE: To investigate difference between the appearance and the bony
      structure in the polysyndactyly of the fifth toe fused with the fourth toe.
      METHODS: From Jan. 2009 to Jan. 2014, 54 patients (65 feet) with polysyndactyly
      of the fifth toe fused with the fourth toe were treated. The appearance, X-ray
      and intraoperative finding were recorded and compared to classify the deformity.
      Then the extra toe was excised and syndactyly was separated. The malalignment and
      brachydactyly of the sixth toes were corrected simultaneously. RESULTS: According
      to the bone and joint type, the fifth toes were neoplastic toes without joints in
      17 feet, or had poor bony and joint alignment with the sixth toes in 48 feet. So
      the fifth toes were excised in all the cases. The patients were followed up for 1
      month to 4 years. The oblique deformity of sixth toes were corrected completely
      with improved length. CONCLUSIONS: The polysyndactyly of the fifth toe fused with
      the fourth toe should be classified to design the excised toe (usually fifth toe)
      and correction procedure. The appearance and bony joint recovery are both
      important.

PMID- 26211183
TI  - [Clinical application of perforator propeller flaps with anastomosis of
      superficial veins].
AB  - OBJECTIVE: To investigate the clinical effect of anastomosis of superficial veins
      for improving the drainage of perforator propeller flaps. METHODS: From Sept.
      2011 to Dec. 2012, 11 cases with soft tissue defects and chronic ulcer wound at
      extremities were treated with adjacent perforator propeller flaps, which were
      pedicled by the peroneal artery(5 cases), or the lateral supramalleolar artery(3
      cases), or the ulnar artery (2 cases), or the posterior interrosseous artery (1
      case). The wound size ranged from from 3.0 cm x 2. 5 cm to 11. 0 cm x 4. 0 cm,
      and the falps size ranged from 6 cm x 3 cm to 21 em x 5 cm. One superficial vein
      in all the flaps was anastomosed with superficial vein in the recipient area. The
      blood supply of the flaps were recorded after operation 1 - 3 months after
      operation, the fluency of anastomosed vein was detected by color Doppler
      ultrasound. Flap swelling evaluations were performed in early 3 months and later
      3 - 6 months, and the results were classified into 4 grading degrees. 6 months
      later, Questionnaire of the flap aesthetic satisfactory was performed for seven
      patients during follow-up period. RESULTS: 9 flaps survived completely, two flaps
      had partial marginal skin necrosis in the distal end, which were both managed
      with surgical debridement, and both wounds healed in two months. 9 cases were
      followed up for more than 12 - 19 months. The early rsults of flap swelling
      evaluations were: I degree 0 case, II degree 8 cases, III degree 3 cases, IV
      degree 0 case, and the later results were: I degree 7 cases, II degree 4 cases,
      III degree 0 case, IV degree 0 case. The flaps had ideal appearance, good
      contour, and high aesthetic satisfactory (100%). The mean flap survival area rate
      of veins anastomosed was (98. 6 +/- 9. 7) %. CONCLUSIONS: Perforator propeller
      flaps with anastomosis of superficial veins can improve the flap venous drainage,
      avoid transient venous venous congestion, so as to increase the flap survival. It
      is an effective way for improving the vein drainage.

PMID- 26211184
TI  - [Clinical application of lateral superior genicular composite tissue flap].
AB  - OBJECTIVE: To investigate the clinical effect of lateral superior genicular
      composite tissue flap for tissue defect. METHODS: The axis line of flap is the
      lateral thigh vertical midline. The cutaneous branch is inserted 4 cm near the
      femoral lateral epicondylus. The anterior border is the elongation line along
      patellar lateral border. The posterior margin is the hinder margin of femoral
      biceps. The lower border is the horizontal line along the upper line of patella.
      The composite flaps were used in 18 cases with soft tissue defects in
      extremities, 11 cases with clacaneus tenden defects and 16 cases with bony
      nonunion. Results From Mar. 2002 to Sept. 2013, 45 cases were treated with the
      composite tissue flaps. The flaps size ranged from 6 cm x 3 cm to 17cm x 9 cm.
      All the flaps survived completely. Blood supply crisis happened in 2 cases, which
      was released by reanastomosis. The patients were followed up for 1 - 2. 5 years
      with satisfactory aesthetic and functional results. All the bone defect and
      nonunion were healed. Good healing was also achieved in donor sites. 8 months
      after operation, knee joint function is evaluated as good by hospital special
      surgery knee score (HSS). CONCLUSION: Lateral superior genicular compostie tissue
      flap can be used to reconstruct soft tissue defect, bone defect and tenden
      calcaneus defect in one stage.

PMID- 26211185
TI  - [Surgical management of temporomandibular joint ankylosis under the guidance of
      navigation].
AB  - OBJECTIVE: To assess the safety and the accuracy of surgical navigation
      technology in the resection of severe ankylosis of the mandibular condyle with
      the middle cranial fossa. METHODS: The CT scan data was transferred to a Windows
      based computer workstation, and the patient' s individual anatomy was assessed in
      multiplanar views at the workstation. In the operation, the patient and the
      virtual image were matched by individual registration with the reference points
      which were set on the skull bone surface and the teeth. Then the real time
      navigation can be performed. RESULTS: The acquisition of the data sets was
      uncomplicated, and image quality was sufficient to assess the operative result in
      three cases. The operations were performed successfully with the guidance of real
      time navigation. The application of surgical navigation have enhanced the safety
      and the accuracy of the surgery for bony ankylosis of temporomandibular joint.
      CONCLUSIONS: The application of surgical navigation can improve the accuracy and
      safety of surgical excision of the ankylosed skull base tissue.

PMID- 26211186
TI  - [The research of SurgiCase CMF software in surgical simulation and prediction for
      mandibular asymmetry].
AB  - OBJECTIVE: To evaluate the predictive accuracy of the SurgiCase CMF software in
      surgical simulation and prediction for mandibular asymmetry with 3-dimensional
      simulation and measurement. METHODS: CBCT data of 27 patients with mandibular
      asymmetry were observed in CMF, and postoperative soft tissue physiognomy were
      predicted by simulating sagittal ramus osteotomy with or without genioplasty. The
      measurement parameters representing the symmetry of soft tissue were selected and
      the horizontal, coronal and sagittal planes were established. The results were
      analyzed by SPSS 19. 0. The overlap compared color grading charts were observed.
      RESULTS: Angles between cheilions and the horizonta plane (Ch-Ch-FH) in the
      simulation and postoperative soft tissues are (2. 35 +/- 1. 81) degrees  and (1.
      44 +/- 1. 13) degrees . The angles constructed among subnasale, upper lip and
      lower lip (Sn-UL-LL) are (4. 02 +/- 3. 05) degrees  and (2. 59 +/- 1. 64) degrees
      , showing statistically different (P < 0. 01, P < 0. 05), which means that
      predictive accuracy of the lip canting and lip vertical deviation is relatively
      low. Distance between gonioi and sagittal plane (Go'-MS), distance between gonion
      and pogonion (Go'-Pog') and angle betweer subnasale to menton and the horizontal
      plane (Sn-Me'-MS) are not statistically different, which mean! high predictive
      accuracy of mandibular angle and chin. By observing the overlap compared color
      gradin-) charts, the predictive accuracy is not good in the cheek, especially in
      the deviate side. CONCLUSIONS: The predictive accuracy of CMF system for patients
      with mandibular asymmetry is relatively high, but it is not good in the lip and
      cheek. The software improvement is still necessary.

PMID- 26211187
TI  - [Clinical research for the treatment of temporomandibular joint injury based on
      three-dimensional digital technology].
AB  - OBJECTIVE: To investigate the accurate and individual treatment of
      temporomandibular joint(TMJ) injury based on 3D digital technology. METHODS:
      Maxillo-mandibular model was made using rapid prototyping technology based on the
      pre-operation 3D CT results. According to the 3D digital measurement results, TMJ
      concepts were ordered and the prosthesis was used to simulate the replacement
      surgery on the model. Then the joint replacement surgery was performed afterward.
      RESULTS: (1)After total replacement of TMJ, no pain happened and mouth open was
      not limited. Three months later, the joint position was normal and stable. The
      month open width was 4 cm. (2)After condyle replacement, primary healing was
      achieved with complete survival of bone graft. No edema was seen. Symmetric
      facial appearance was satisfactory. CONCLUSIONS: Bilateral individual prosthesis
      for total TMJ or condyle replacement is an ideal method for TMJ injury.

PMID- 26211189
TI  - INTRODUCING: AMERICAN ASSOCIATION FOR PHYSICIAN LEADERSHIP.

PMID- 26211188
TI  - [In vitro study of TGF-beta1-induced epithelial-mesenchymal transition of keloid
      epithelial cells].
AB  - OBJECTIVE: To construct and characterize the TGF-beta1, induced epithelial
      mesenchymal transition (EMT) model of keloid epithelial cells in vitro, and to
      investigate the expression of epithelial stem cells related surface markers in
      keloid epithelial cells during EMT induction. METHODS: The epithelial cells from
      3 keloid samples of ears were cultured in vitro and induced by transforming
      growth factor betal (TGF-beta1, 1 ng/ml) for 5 days, which was the experimental
      group, the same cells untreated were considered as the negative control group.
      The expressions of EMT-associated markers and regulative genes were detected
      using immunofluorescence staining, real-time PCR and western blot analysis. Then
      the surface markers of epithelial stem cells were detected using real-time PCR.
      Statistical significance was determined using Independent-Samples t Test, a p
      value less than 0. 05 was considered statistically significant. RESULTS: The mRNA
      expression of transcription factor snail2 and mesenchymal-specific marker
      vimentin increased significantly in TGF-beta1, induced keloid epithelial cells (P
      < 0. 05), in which snail2 increasing from 0. 91 +/- 0. 23 to 1. 69 +/- 0. 10, and
      vimentin from 5. 86 +/- 2. 07 to 24. 29 +/- 5. 39. Whereas the mRNA expression of
      epithelial-specific marker E-cadherin decreased from 1. 06 +/- 0. 19 to 0. 65 +/-
      0. 09. The mRNA expression of CD29 and Lgr6, two surface markers of epithelial
      stem cells, significantly increased after induction of the TGF-beta1, (P < 0.
      05), from 0. 55 +/- 0. 14 and 1. 61 +/- 0. 31 to 1. 19 +/- 0. 12 and 3. 84 t 0.
      62 respectively. In induced cells, the immunofluorescence results showed staining
      of E- cadherin became faint, but the number of positive staining cells of
      vimentin increased. Western blot confirmed the protein expression of E-cadherin
      weakened, and the vimentin and p-Smad3 enhanced (P < 0. 05). CONCLUSIONS: TGF
      beta1, initiated EMT in keloid epithelial cells by inducing the up-regulation of
      snail2, and TGF-beta1,/Smad3 signaling pathway was involved in EMT. EMT could
      change the phenotype of epithelial stem cells in keloid.

PMID- 26211190
TI  - UNDERSTANDING PHYSICIAN ENGAGEMENT - AND HOW TO INCREASE IT.

PMID- 26211191
TI  - ROADMAP FOR PHYSICIAN COMPENSATION IN A VALUE-BASED WORLD.

PMID- 26211192
TI  - HEALTH CARE REFORM AND LEADERSHIP: SWITCHING FROM VOLUME TO VALUE.

PMID- 26211193
TI  - WILL PATIENTS' HAPPINESS LEAD TO BETTER HEALTH? THE ACA AND REIMBURSEMENTS.

PMID- 26211194
TI  - ADDRESSING THE PROBLEMS OF OUTPATIENT OBSERVATIONS VS. SHORT-STAY INPATIENT
      ADMISSIONS.

PMID- 26211195
TI  - HOME-BASED PRIMARY CARE: A VA INNOVATION COMING SOON.

PMID- 26211196
TI  - DOES PAYER STATUS PREDICT CD4 CELL COUNT AND HIV VIRAL LOAD?

PMID- 26211197
TI  - THE ACA AND THE SAFETY NET: CHALLENGES AND SOLUTIONS.

PMID- 26211198
TI  - FREE MARKETS AND HEALTH CARE.

PMID- 26211199
TI  - TEAM DYNAMICS IN CLINICAL INFORMATICS.

PMID- 26211200
TI  - THE DREADED DRAMA TRIANGLE.

PMID- 26211202
TI  - SERVING ON BOARDS: CAVEATS FOR PHYSICIAN LEADERS.

PMID- 26211201
TI  - THE IMPACT OF AN EXECUTIVE LEADERSHIP DEVELOPMENT PROGRAM.

PMID- 26211203
TI  - THE VALUE OF VOLUNTEERING.

PMID- 26211204
TI  - MEDICAL MISSIONS: DO NO HARM?

PMID- 26211205
TI  - FRONTIER WORK IN THE REMOTE HIGHLANDS OF PAPUA NEW GUINEA.

PMID- 26211206
TI  - DIRECT PRIMARY CARE PRACTICE MODEL DROPS INSURANCE AND GAINS PROVIDERS AND
      CONSUMERS.

PMID- 26211207
TI  - LEADING HEALTH SYSTEMS SWITCH FOCUS FROM GENETICS TO GENOMICS.

PMID- 26211208
TI  - STRATEGIC TEAMWORK IN HEALTH CARE: THE ESSENTIAL ROLE OF PHYSICIANS.

PMID- 26211209
TI  - GREAT PHYSICIAN ENGAGEMENT IS KEY TO GREAT QUALITY.

PMID- 26211210
TI  - MIGRATING CARE: HOW THE ACA DOES AND DOES NOT ADDRESS UNDOCUMENTED IMMIGRATION.

PMID- 26211211
TI  - WILL THE AFFORDABLE CARE ACT SURVIVE 2015? CONGRESS, THE SUPREME COURT AND
      POLITICAL REALITY.

PMID- 26211212
TI  - JOB CRISIS: THE OPPORTUNITY OF A LIFETIME.

PMID- 26211213
TI  - IMPROVING SAFE PATIENT THROUGHPUT IN A MULTIDISCIPLINARY ONCOLOGY CLINIC.

PMID- 26211214
TI  - INTEGRATING HEALTH LITERACY INTO ORGANIZATIONAL STRUCTURE.

PMID- 26211215
TI  - THE NEED FOR PHYSICIAN LEADERSHIP TRAINING: A SURVEY OF THE AMERICAN SOCIETY OF
      PEDIATRIC OTOLARYNGOLOGY MEMBERS.

PMID- 26211216
TI  - LEADERSHIP TRAINING FOR RESIDENTS: A NOVEL APPROACH.

PMID- 26211217
TI  - WHAT ARE YOU REALLY SAYING?

PMID- 26211218
TI  - A Logical Method of Selecting an Approach for Amplatzer Septal Occluder
      Implantation: Using Transesophageal Echocardiography to Reduce Procedure
      Durations and Avoid Complications.
AB  - Percutaneous closure of atrial septal defects using an Amplatzer Septal Occluder
      (ASO) has recently become the procedure of first choice. However, when ASO
      deployment is difficult, procedures may be prolonged and complications may occur.
      We investigated a method for identifying cases in which ASO deployment would be
      difficult. After retrospectively identifying 70 patients (age: 4.1-70.4 years;
      body weight: 15.6-77.3 kg) who underwent atrial septal defect closure using an
      ASO in 2007 or later, we classified them into three groups: Group A, implantation
      by a conventional approach; Group B, implantation by a right upper pulmonary vein
      approach, and Group C,. change from a conventional to a right upper pulmonary
      vein approach. Characteristics of the groups were compared. Individually, none of
      the investigated characteristics was suitable for identifying difficult cases.
      Furthermore, we observed no consistent trends between aortic rim deficiency and
      ASO diameter, or between SG/IAS angle, which is the angle formed by the super
      stiff guidewire (SG) and the intra-atrial septum (IAS). However, the ASO diameter
      divided by the diameter of the left atrium (ASO/LA) correlated with the SG/IAS
      angle in Group C. Using this correlation, ASO implantation is predicted to be
      difficult in patients with an ASO/LA (%) ratio exceeding the (SG/IAS angle) x
      1.44 + 48.1, which represents the 95th percentile of Group C. Graphing the SG/IAS
      angle and the ASO/LA ratio can identify cases in which ASO implantation may be
      difficult. We consider this method of selecting an approach to be extremely
      useful for avoiding various risks.

PMID- 26211219
TI  - Ten Cases of Colovesical Fistula due to Sigmoid Diverticulitis.
AB  - Colovesical fistula (CVF) resulting from colon diverticulosis is a comparatively
      rare disease, and neither the diagnosis nor treatment has been established. Our
      experience with CVF due to sigmoid diverticulitis over a 9-year period was
      reviewed to clarify the clinical presentation and diagnostic confirmation. Ten
      patients with CVF were identified in this period, and chief complaints,
      laboratory findings, presenting symptoms, diagnostic investigations, and
      subsequent treatments were reviewed. Preoperative urinalysis showing bacteriuria
      (100%) was the most common presentation, followed by fecaluria (40%), abdominal
      pain (40%), pneumaturia (30%), hematuria (30%), pain on urination (30%),
      pollakiuria (10%), and dysuria (10%). The abilities of various preoperative
      investigations to identify CVF were: computed tomography (CT), 88.9%; magnetic
      resonance imaging, 40%; cystoscopy, 30%, and gastrografin irrigoscopy, 22.2%.
      Colonoscopy (0%) was not diagnostic. Bowel resection was performed in nine of ten
      patients. When inflammation was intense, covering ileostomy was performed, and an
      omental plasty was placed between the bowel anastomosis and bladder. When CVF is
      suspected, we recommend CT followed by colonoscopy and cystoscopy as a first-line
      investigation to rule out malignancy as a cause. Other modalities should only be
      used if the diagnosis is in doubt or additional information is needed to plan
      operative management. Primary colic anastomosis appears to be safely performed by
      applying omental plasty and covering ileostomy.

PMID- 26211220
TI  - Additional Value of Diffusion-weighted MRI to Gd-EOB-DTPA-enhanced Hepatic MRI
      for the Detection of Liver Metastasis: the Difference Depending on the Experience
      of the Radiologists.
AB  - This retrospective study was to investigate whether adding diffusion-weighted
      imaging (DWI) to Gd-EOB-DTPA-enhanced MRI (EOB-MRI) improved the detection of
      liver metastasis in radiology resident and board-certified radiologist groups. It
      was approved by our institutional review board. We selected 18 patients with 35
      liver metastases and 12 patients without liver tumors. Five board-certified
      radiologists and 5 radiology residents participated in the observer performance
      study. Each observer first interpreted T1- and T2-weighted-, plain-, arterial
      phase-, and hepatobiliary phase images and specified the location of the liver
      metastases. The software subsequently displayed the DWI images simultaneously and
      all participants repeated the reading. We used Jackknife alternative free
      response receiver operating characteristic (JAFROC) analysis to compare the
      observer performance in detecting liver metastases. The mean values for the area
      under the curve (AUC) for EOB-MRI without and with DWI were 0.78 +/- 0.13
      [standard deviation: SD] and 0.87 +/- 0.09, respectively, for the radiology
      residents, and the difference was statistically significant (p = 0.045). For the
      board- certified radiologists these values were 0.92 +/- 0.02 and 0.96 +/- 0.01,
      respectively, and the difference was not statistically significant (p = 0.092).
      EOB-MRI with DWI significantly improved the performance of radiology residents in
      the identification of liver metastases.

PMID- 26211221
TI  - Possible Contribution of a Diverticulum to the Development and Rupture of Colonic
      Lymphangioma.
AB  - A 55-year-old Japanese man with a history of diverticulitis underwent colonoscopy
      for careful evaluation of progressive anemia. A 5-mm depressed lesion oozing
      spontaneously was observed at the hepatic flexure. On suspicion of depressed-type
      of cancer, right-sided hemicolectomy was performed. Histopathological examination
      indicated a collapsed lymphangioma exactly over a diverticulum, which had
      previously been complicated diverticulitis. The colonic mucosa and lymphangioma
      prolapsed beyond the subserosal layer via the muscularis propria defect,
      resulting in a depressed lesion and mucosal laceration with hemorrhage. This case
      suggests the contribution of a colonic diverticulum to the development and
      rupture of lymphangioma, which needed to be distinguished from depressed-type
      colon cancer.

PMID- 26211222
TI  - Laparoscopic Repair and Percutaneous Endoscopic Gastrostomy to Treat Giant
      Esophageal Hiatal Hernia with Gastric Obstruction: A Case Report.
AB  - We describe a 74-year-old man with repeated aspiration pneumonia who developed
      gastric obstruction due to giant esophageal hiatal hernia (EHH). We repaired the
      giant EHH by laparoscopic surgery and subsequently anchored the stomach to the
      abdominal wall by percutaneous endoscopic gastrostomy (PEG) using
      gastrofiberscopy. Thereafter, the patient resumed oral intake and was discharged
      on postoperative day 21. At two years after these procedures, the patient has
      adequate oral intake and lives at home. Because this condition occurs more
      frequently in the elderly with comorbidities, laparoscopic surgery contributes to
      minimally invasive treatment. Furthermore, the procedure combined with concurrent
      gastropexy via PEG is useful for treating patients who have difficulty swallowing
      and for preventing recurrent hernia.

PMID- 26211223
TI  - Creating a new normal.

PMID- 26211224
TI  - Taking stock of ACO launches.

PMID- 26211225
TI  - Population health progress report.

PMID- 26211226
TI  - Taking ICD-10 from burden to strategic opportunity.

PMID- 26211227
TI  - Handling the demands of a population boom. Using RTLS to improve patient care and
      workflows.

PMID- 26211229
TI  - Tagging assets in 2020. What do four RTLS executives foresee about their tagging
      technology's reach and utility five years from now?

PMID- 26211228
TI  - Fighting infection with RTLS.

PMID- 26211230
TI  - Our expert trio takes on the cloud.

PMID- 26211231
TI  - Like playing jazz. An automated check-in solution greater than the sum of its
      parts.

PMID- 26211232
TI  - Building trust is key to HIE success.

PMID- 26211233
TI  - HL7 launches Argonaut Project to advance FHIR interoperability standard.

PMID- 26211234
TI  - Stage 2 was no failure. The case for a shorter Meaningful Use reporting period.

PMID- 26211235
TI  - [Exercise-sensitive Indices Screening from Electrocardiogram Based on Rest
      workload Alternating Pattern].
AB  - Heart rate is the most common index to directly monitor the level of physical
      stress by comparing the subject's heart rate with an appropriate "target heart
      rate" during exercise. However, heart rate only reveals the cardiac rhythm of the
      complex cardiovascular changes that take place during exercise. It is essential
      to get the dynamic response of the heart to exercise with various indices instead
      of only one single measurement. Based on the rest-workload alternating pattern,
      this paper screens the sensitive indices of exercise load from electrocardiogram
      (ECG) rhythm and waveform, including 4 time domain indices and 4 frequency domain
      indices of heart rate variability (HRV), 3 indices of waveform similarity and 2
      indices of high frequency noise. In conclusion, RR interval (heart rate) is a
      reliable index for the realtime monitoring of exercise intensity, which has
      strong linear correlation with load intensity. The ECG waveform similarity and
      HRV indices are useful for the evaluation of exercise load.

PMID- 26211236
TI  - [Automatic Classification of Epileptic Electroencephalogram Signal Based on
      Improved Multivariate Multiscale Entropy].
AB  - Traditional sample entropy fails to quantify inherent long-range dependencies
      among real data. Multiscale sample entropy (MSE) can detect intrinsic
      correlations in data, but it is usually used in univariate data. To generalize
      this method for multichannel data, we introduced multivariate multiscale entropy
      into multiscale signals as a reflection of the nonlinear dynamic correlation. But
      traditional multivariate multiscale entropy has a large quantity of computation
      and costs a large period of time and space for more channel system, so that it
      can not reflect the correlation between variables timely and accurately. In this
      paper, therefore, an improved multivariate multiscale entropy embeds on all
      variables at the same time, instead of embedding on a single variable as in the
      traditional methods, to solve the memory overflow while the number of channels
      rise, and it is more suitable for the actual multivariate signal analysis. The
      method was tested in simulation data and Bonn epilepsy dataset. The simulation
      results showed that the proposed method had a good performance to distinguish
      correlation data. Bonn epilepsy dataset experiment also showed that the method
      had a better classification accuracy among the five data set, especially with an
      accuracy of 100% for data collection of Z and S.

PMID- 26211237
TI  - [Realization of Heart Sound Envelope Extraction Implemented on LabVIEW Based on
      Hilbert-Huang Transform].
AB  - We proposed a research of a heart sound envelope extraction system in this paper.
      The system was implemented on LabVIEW based on the Hilbert-Huang transform (HHT).
      We firstly used the sound card to collect the heart sound, and then implemented
      the complete system program of signal acquisition, pretreatment and envelope
      extraction on LabVIEW based on the theory of HHT. Finally, we used a case to
      prove that the system could collect heart sound, preprocess and extract the
      envelope easily. The system was better to retain and show the characteristics of
      heart sound envelope, and its program and methods were important to other
      researches, such as those on the vibration and voice, etc.

PMID- 26211238
TI  - [Evoked Potential Blind Extraction Based on Fractional Lower Order Spatial Time
      Frequency Matrix].
AB  - The impulsive electroencephalograph (EEG) noises in evoked potential (EP) signals
      is very strong, usually with a heavy tail and infinite variance characteristics
      like the acceleration noise impact, hypoxia and etc., as shown in other special
      tests. The noises can be described by a stable distribution model. In this paper,
      Wigner-Ville distribution (WVD) and pseudo Wigner-Ville distribution (PWVD) time
      frequency distribution based on the fractional lower order moment are presented
      to be improved. We got fractional lower order WVD (FLO-WVD) and fractional lower
      order PWVD (FLO-PWVD) time-frequency distribution which could be suitable for a
      stable distribution process. We also proposed the fractional lower order spatial
      time-frequency distribution matrix (FLO-STFM) concept. Therefore, combining with
      time-frequency underdetermined blind source separation (TF-UBSS), we proposed a
      new fractional lower order spatial time-frequency underdetermined blind source
      separation (FLO-TF-UBSS) which can work in a stable distribution environment. We
      used the FLO-TF-UBSS algorithm to extract EPs. Simulations showed that the
      proposed method could effectively extract EPs in EEG noises, and the separated
      EPs and EEG signals based on FLO-TF-UBSS were almost the same as the original
      signal, but blind separation based on TF-UBSS had certain deviation. The
      correlation coefficient of the FLO-TF-UBSS algorithm was higher than the TF-UBSS
      algorithm when generalized signal-to-noise ratio (GSNR) changed from 10 dB to 30
      dB and a varied from 1. 06 to 1. 94, and was approximately e- qual to 1. Hence,
      the proposed FLO-TF-UBSS method might be better than the TF-UBSS algorithm based
      on second order for extracting EP signal under an EEG noise environment.

PMID- 26211239
TI  - [Analysis of Electroencephalogram Sample Entropy Measurement in Frontal
      Association Cortex Based on Heroin-induced Conditioned Place Preference in Rats].
AB  - To explore the relationship between the drug-seeking behavior, motivation of
      conditioned place preference (CPP) rats and the frontal association cortex (FrA)
      electroencephalogram (EEG) sample entropy, we in this paper present our studies
      on the FrA EEG sample entropy of control group rats and CPP group rats,
      respectively. We invested different behavior in four situations of the rat
      activities, i. e. rats were staying in black chamber of videoed boxes, those
      staying in white chamber of videoed boxes, those shuttling between black-white
      chambers and those shuttling between white-black chambers. The experimental
      results showed that, compared with the control group rats, the FrA EEG sample
      entropy of CPP rats staying in black chamber of video box and shuttling between
      white-black chambers had no significant difference. However, sample entropy is
      significantly smaller (P < 0.01) when heroin-induced group rats stayed in white
      chamber of video box and shuttled between black-white chambers. Consequently, the
      drug-seeking behavior and motivation of CPP rats correlated closely with the EEG
      sample entropy changes.

PMID- 26211240
TI  - [Multi-channel Synchronization Analysis of Mild Cognitive Impairment in Type 2
      Diabetes Patients].
AB  - The cognitive impairment of type 2 diabetes patients caused by long-term
      metabolic disorders has been the current focus of attention. In order to find the
      related electroencephalogram (EEG) characteristics to the mild cognitive
      impairment (MCI) of diabetes patients, this study analyses the EEG
      synchronization with the method of multichannel synchronization analysis--S
      estimator based on phase synchronization. The results showed that the S estimator
      values in each frequency band of diabetes patients with MCI were almost lower
      than that of control group. Especially, the S estimator values decreased
      significantly in the delta and alpha band, which indicated the EEG
      synchronization decrease. The MoCA scores and S value had a significant positive
      correlation in alpha band.

PMID- 26211241
TI  - [De-noising of Impedance Cardiography Differential Signal and Detection of the
      Feature Points Based on Wavelet Transformation].
AB  - Calculation of cardiac hemodynamic parameters is based on accurate detection of
      feature points in impedance cardiogram. According to these parameters, doctors
      can determine heart conditions, so it is very important to accurately detect the
      feature point of impedance differential signals. This article presents a process
      in which we used wavelet threshold method to de-noise signals, and then detected
      the feature points after six layers wavelet decomposition by using bior3. 7. The
      experimental data were collected from healthy persons in our laboratory and
      twenty two clinical patients in Chongqing Daping Hospital by using KF_ICG
      instrument. The results indicated that this method could precisely detect feature
      points whether it was from healthy people or clinical patients. This helps to
      achieve the application of noninvasive detection cardiac hemodynamic parameters
      in clinical treatments by using impedance method.

PMID- 26211242
TI  - [Research on Constant-current Characteristics of Howland Current Source Used in
      Bioelectrical Impedance Detection].
AB  - This study aims to analyze and improve Howland current source circuit and to
      study the constant current source of alternating current with high output
      impedance and high stability. A simulation study was carried out on the constant
      current characteristics of Howland current source from two aspects of resistance
      match value and the selection of Op amp parameters, and then the output impedance
      was analyzed. The simulation experiment showed that when it was with the best
      matched resistance, the constant-current characteristics of Howland current
      source was better. Op amp parameters could affect the constant-current
      characteristics of Howland current source. In Howland current source circuit, the
      current source after parameter optimization had better output impedance and load
      capacity. The results showed that there was the best matched resistance in the
      selection by Howland current source. The Op amp with large broadband, high slew
      rate and open loop gain, and wide range of power supply voltage is more suitable
      for the bioelectrical impedance detection circuit.

PMID- 26211243
TI  - [Analysis of Electric Stress in Human Head in High-frequency Low-power
      Electromagnetic Environment].
AB  - Action of electromagnetic radiation exerting on human body has been a concerned
      issue for people. Because electromagnetic waves could generate an electric stress
      in a discontinuous medium, we used the finite difference time domain (FDTD) as
      calculation methods to calculate the electric stress and its distribution in
      human head caused by high-frequency low-power electromagnetic environment, which
      was generated by dual-band (900 MHz and 1 800 MHz) PIFA antennas with radiated
      power 1 W, and we then performed the safety evaluation of cell phone radiation
      from the angle whether the electric stress further reached the human hearing
      threshold. The result showed that there existed the electric stress at the
      interface of different permittivity organization caused by the two kinds of high
      frequency low-power electromagnetic environment and the maximum electric stress
      was located at the interface between skin and air of the phone side, and the
      electric stress peak at skull did not reach the threshold of auditory caused by
      bone tissue conduction so that it can not produce auditory effects.

PMID- 26211244
TI  - [Research on Energy Distribution During Osteoarthritis Treatment Using Shock Wave
      Lithotripsy].
AB  - Extracorporeal shock wave treatment is capable of providing a non-surgical and
      effective treatment modality for patients suffering from osteoarthritis. The
      major objective of current works is to investigate how the shock wave (SW) field
      would change if a bony structure exists in the path of the acoustic wave.
      Firstly, a model of finite element method (FEM) was developed based on Comsol
      software in the present study. Then, high-speed photography experiments were
      performed to record cavitation bubbles with the presence of mimic bone. On the
      basis of comparing experimental with simulated results, the effectiveness of FEM
      model could be verified. Finally, the energy distribution during extracorporeal
      shock wave treatment was predicted. The results showed that the shock wave field
      was deflected with the presence of bony structure and varying deflection angles
      could be observed as the bone shifted up in the z-direction relative to shock
      wave geometric focus. Combining MRI/CT scans to FEM modeling is helpful for
      better standardizing the treatment dosage and optimizing treatment protocols in
      the clinic.

PMID- 26211245
TI  - [Finite Element Analysis of Effect of Key Dimension of Nitinol Stent on Its
      Fatigue Behaviour].
AB  - To evaluate the fatigue behavior of nitinol stents, we used the finite element
      method to simulate the manufacture processes of nitinol stents, including
      expanding, annealing, crimping, and releasing procedure in applications of the
      clinical treatments. Meanwhile, we also studied the effect of the crown area
      dimension of stent on strain distribution. We then applied a fatigue diagram to
      investigate the fatigue characteristics of nitinol stents. The results showed
      that the maximum strain of all three stent structures, which had different crown
      area dimensions under vessel loads, located at the transition area between the
      crown and the strut, but comparable deformation appeared at the inner side of the
      crown area center. The cause, of these results was that the difference of the
      area moment of inertia determined by the crown dimension induced the difference
      of strain distribution in stent structure. Moreover, it can be drawn from the
      fatigue diagrams that the fatigue performance got the best result when the crown
      area dimension equaled to the intermediate value. The above results proved that
      the fatigue property of nitinol stent had a close relationship with the dimension
      of stent crown area, but there was no positive correlation.

PMID- 26211246
TI  - [Research on the Surface Potential Distribution of Spinal Cord Based on Finite
      Element Analysis].
AB  - Finite element analysis can be used to study the change of the structure and the
      interior field intensity of human and animal body organs and tissues with
      simulation experiment. We in our research used finite element analysis software
      to analyze and solve the spinal cord surface potential problems, and investigated
      the transmission features of signals generated by interneurons in spinal nerves
      which were related with body motion control and sensory processing. A three
      dimensional model of electrical source in rat spinal cord was built, and the
      influence on potential distribution on spinal cord surface caused by position
      changes of electrical source in transverse direction and dorsoventral direction
      were analyzed and calculated. We obtained the potential distribution curves of
      spinal cord surface and found that the potential distribution on spinal cord
      surface showed monotone. In addition, potentials of some registration points were
      smaller than that of registration points around.

PMID- 26211247
TI  - [Three-dimensional Finite Element Analysis of Biomechanical Effect of Rigid
      Fixation and Elastic Fixation on Lumbar Interbody Fusion].
AB  - This study was aimed to compare the mechanical characteristics under different
      physiological load conditions with three-dimensional finite element model of
      rigid fixation and elastic fixation in the lumbar. We observed the stress
      distribution characteristics of a sample of healthy male volunteer modeling under
      vertical, flexion and extension torque situation. The outcomes showed that there
      existed 4-6 times pressure on the connecting rod of rigid fixation compared with
      the elastic fixations under different loads, and the stress peak and area of
      force on elastic fixation were much higher than that of the rigid fixations. The
      elastic fixation has more biomechanical advantages than rigid fixation in
      promoting interbody lumbar fusion after surgery.

PMID- 26211248
TI  - [Research on Hemorheology in Rats with Acute Hyperuricemia].
AB  - Hyperuricemia is a risk factor for various diseases, but knowledge on acute
      hyperuricemia is still not sufficient. The present study was aimed to investigate
      the effect of acute hyperuricemia on red blood cells from hemorheological point
      of view, and to provide the reference for clinical treatment. The rats were
      gavaged with 500 mg/kg hypoxanthine and intraperitoneally injected with 100 mg/kg
      oxonate to induce the model of acute hyperuricemia. The same volume of blood
      samples were drawn within time period of 0, 1, 2, 3 and 6 h, respectively, from
      the inner canthus of rats to measure the serum uric acid, hemorheological
      parameters and the malondialdehyde level. It was found that in each period of 1,
      2 and 3 h, the rats had significantly higher levels of uric acid. The integrated
      deformation index and relax index were increased. The hemolysis rate was
      significantly reduced. The plasma malondialdehyde level was obviously decreased
      at the end of 2 h. The results suggested that short-term elevated uric acid could
      improve the hemorheological parameters and the lipid oxidative level in red blood
      cells.

PMID- 26211249
TI  - [Equivalent Lever Principle of Ossicular Chain and Amplitude Reduction Effect of
      Internal Ear Lymph].
AB  - This paper makes persuasive demonstrations on some problems about the human ear
      sound transmission principle in existing physiological textbooks and reference
      books, and puts forward the authors' view to make up for its literature. Exerting
      the knowledge of lever in physics and the acoustics theory, we come up with an
      equivalent simplified model of manubrium mallei which is to meet the requirements
      as the long arm of the lever. We also set up an equivalent simplified model of
      ossicular chain--a combination of levers of ossicular chain. We disassemble the
      model into two simple levers, and make full analysis and demonstration on them.
      Through the calculation and comparison of displacement amplitudes in both
      external auditory canal air and internal ear lymph, we may draw a conclusion that
      the key reason, which the sound displacement amplitude is to be decreased to
      adapt to the endurance limit of the basement membrane, is that the density and
      sound speed in lymph is much higher than those in the air.

PMID- 26211250
TI  - [A New Method to Segment Multiple Sclerosis Lesions Using Multispectral Magnetic
      Resonance Images].
AB  - Magnetic resonance (MR) images can be used to detect lesions in the brains of
      patients with multiple sclerosis (MS). An automatic method is presented for
      segmentation of MS lesions using multispectral MR images in this paper. Firstly,
      a Pd-w image is subtracted from its corresponding T1-w images to get an image in
      which the cerebral spinal fluid (CSF) is enhanced. Secondly, based on kernel
      fuzzy c-means clustering (KFCM) algorithm, the enhanced image and the
      corresponding T2-w image are segmented respectively to extract the CSF region and
      the CSF-MS lesions combinatoin region. A raw MS lesions image is obtained by
      subtracting the CSF region from CSF-MS region. Thirdly, based on applying median
      filter and thresholding to the raw image, the MS lesions were detected finally.
      Results were tested on BrainWeb images and evaluated with Dice similarity
      coefficient (DSC), sensitivity (Sens), specificity (Spec) and accuracy (Acc). The
      testing results were satisfactory.

PMID- 26211251
TI  - [Research on Three-dimensional Medical Image Reconstruction and Interaction Based
      on HTML5 and Visualization Toolkit].
AB  - Integrating visualization toolkit and the capability of interaction,
      bidirectional communication and graphics rendering which provided by HTML5, we
      explored and experimented on the feasibility of remote medical image
      reconstruction and interaction in pure Web. We prompted server-centric method
      which did not need to download the big medical data to local connections and
      avoided considering network transmission pressure and the three-dimensional (3D)
      rendering capability of client hardware. The method integrated remote medical
      image reconstruction and interaction into Web seamlessly, which was applicable to
      lower-end computers and mobile devices. Finally, we tested this method in the
      Internet and achieved real-time effects. This Web-based 3D reconstruction and
      interaction method, which crosses over internet terminals and performance limited
      devices, may be useful for remote medical assistant.

PMID- 26211252
TI  - [Bioinformatics Analysis of Clustered Regularly Interspaced Short Palindromic
      Repeats in the Genomes of Shigella].
AB  - This study was aimed to explore the features of clustered regularly interspaced
      short palindromic repeats (CRISPR) structures in Shigella by using
      bioinformatics. We used bioinformatics methods, including BLAST, alignment and
      RNA structure prediction, to analyze the CRISPR structures of Shigella genomes.
      The results showed that the CRISPRs existed in the four groups of Shigella, and
      the flanking sequences of upstream CRISPRs could be classified into the same
      group with those of the downstream. We also found some relatively conserved
      palindromic motifs in the leader sequences. Repeat sequences had the same group
      with corresponding flanking sequences, and could be classified into two different
      types by their RNA secondary structures, which contain "stem" and "ring". Some
      spacers were found to homologize with part sequences of plasmids or phages. The
      study indicated that there were correlations between repeat sequences and
      flanking sequences, and the repeats might act as a kind of recognition mechanism
      to mediate the interaction between foreign genetic elements and Cas proteins.

PMID- 26211253
TI  - [Application Status of Evaluation Methodology of Electronic Medical Record:
      Evaluation of Bibliometric Analysis].
AB  - In order to provide a reference and theoretical guidance of the evaluation of
      electronic medical record (EMR) and establishment of evaluation system in China,
      we applied a bibliometric analysis to assess the application of methodologies
      used at home and abroad, as well as to summarize the advantages and disadvantages
      of them. We systematically searched international medical databases of Ovid
      MEDLINE, EBSCOhost, EI, EMBASE, PubMed, IEEE, and China's medical databases of
      CBM and CNKI between Jan. 1997 and Dec. 2012. We also reviewed the reference
      lists of articles for relevant articles. We selected some qualified papers
      according to the pre-established inclusion and exclusion criteria, and did
      information extraction and analysis to the papers. Eventually, 1 736 papers were
      obtained from online database and other 16 articles from manual retrieval. Thirty
      five articles met the inclusion and exclusion criteria and were retrieved and
      assessed. In the evaluation of EMR, US counted for 54.28% in the leading place,
      and Canada and Japan stood side by side and ranked second with 8.58%,
      respectively. For the application of evaluation methodology, Information System
      Success Model, Technology Acceptance Model (TAM), Innovation Diffusion Model and
      Cost-Benefit Access Model were widely applied with 25%, 20%, 12.5% and 10%,
      respectively. In this paper, we summarize our study on the application of
      methodologies of EMR evaluation, which can provide a reference to EMR evaluation
      in China.

PMID- 26211254
TI  - [Study of Image Quality Comparison Based on the MTF Method Between Different
      Medical Rigid Endoscopes in an In Vitro Model].
AB  - This study was aimed to use the method of modulation transfer function (MTF) to
      compare image quality among three different Olympus medical rigid cystoscopes in
      an in vitro model. During the experimental processes, we firstly used three
      different types of cystoscopes (i. e. OLYMPUS cystourethroscopy with FOV of 12
      degrees, OLYMPUS Germany A22003A and OLYMPUS A2013A) to collect raster images at
      different brightness with industrial camera and computer from the resolution
      target which is with different spatial frequency, and then we processed the
      collected images using MALAB software with the optical transfer function MTF to
      obtain the values of MTF at different brightness and different spatial frequency.
      We then did data mathematical statistics and compared imaging quality. The
      statistical data showed that all three MTF values were smaller than 1. MTF values
      with the spatial frequency gradually increasing would decrease approaching 0 at
      the same brightness. When the brightness enhanced in the same process at the same
      spatial frequency, MTF values showed a slowly increasing trend. The three
      endoscopes' MTF values were completely different. In some cases the MTF values
      had a large difference, and the maximum difference could reach 0.7. Conclusion
      can be derived from analysis of experimental data that three Olympus medical
      rigid cystoscopes have completely different imaging quality abilities. The No. 3
      endoscope OLYMPUS A2013A has low resolution but high contrast. The No. 1
      endoscope OLYMPUS cystourethroscopy with FOV of 12 degrees, on the contrary, had
      high resolution and lower contrast. The No. 2 endoscope OLYMPUS Germany A22003A
      had high contrast and high resolution, and its image quality was the best.

PMID- 26211255
TI  - [Design of Balance Function Telerehabilitation System Based on C/S].
AB  - This article shows a new design of telerehabilitation system for balance function
      assessment and training in our laboratory. The system is based on C/S network
      architecture, and realizes the telecommunication through socket network
      communication technology. It implements the teletransmission of training data and
      assessment report of sit-down and stand-up, online communication between doctors
      and patients, and doctors'management of patient information. This system realizes
      remote evaluation and telerehabilitation of patients, and brings great
      convenience for the patients.

PMID- 26211256
TI  - [System Design of a Medical Constnt Temperature Flushing Pump].
AB  - The flushing pump which is applied to clean operative wound has no temperature
      controlling function up to now, and doctors have to prepare the flushing fluid
      that has previously been warmed. The flushing pump system with medical constant
      temperature designed in our laboratory can absorb flushing fluid at the room
      temperature, and then eject flushing fluid with the temperature in accordance
      with the requirements of operations at a controlled constant flow rate. The
      system combines flow rate control with temperature control functions. The
      flushing pump system includes flushing part, temperature controlling part, key
      inputting part, liquid crystal displaying part and exceptional situation
      monitoring part. The present paper introduces the design method and principle of
      each part of the system at first, and then gives the debug method of all the
      system parameters. Finally the paper discusses the performance of the system
      according to the result of the experiment.

PMID- 26211257
TI  - [Effect of Gold (Au) Nanoparticles Modified by Surface Chemistry on the
      Proliferation and Migration of Hepatocellular Carcinoma Cells in Vitro].
AB  - Due to the good tumor-targeting and excellent biocompatibility, the drug-loading
      nanoparticles (NPs) has been widely applied in the diagnosis and treatment of
      cancer. However, after the NPs are recognized and internalized by cancer cells,
      the effects of NPs on cell migration behavior were unclear. In the present study,
      the self-assembly techniques (SAMs) was used to modify gold (Au) nanoparticles
      (Au NPs) with different chemical functional groups (CH3, OH, COOH and NH2) as
      model NPs. The dispersion of these groups in solution and the distribution in
      cells were studied by transmission electron microscope (TEM), respectively, and
      the proliferation was examined by MTT assay in vitro. The wound-healing and the
      Transwell assay were used to examine the effect of internalized Au-NPs on HepG2
      cells migration. The results showed that different Au-NPs mainly distributed at
      the edge of the vesicle membrane and the gap between cells. The Au-NPs resulted
      in decreased cell viability in a concentration-depended manner. In addition, the
      results of wound-healing and Transwells assay indicated that the internalization
      of the NH2-NPs and OH-NPs would inhibit cell migration compared with those in the
      control group.

PMID- 26211258
TI  - [Cytotoxicity in Vitro of a Noval Ni-free ZrCuFeAlAg Bulk Metallic Glass].
AB  - This paper is to evaluate the biocompatibility and cytotoxicity of a new Ni-free
      Zr-based bulk metallic glass (BMG), Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3, by
      comparing it with conventional Ti6Al4V alloy. According to ISO 10993-5: 1999 and
      GB/T 16886.5-1997 standards, Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3, pure Zr and
      Ti6Al4V materials were extracted with surface area of sample/volume of medium
      ratio being 1 cm2/mL and 0.5 cm2/mL, respectively. The viabilities of MG-63 cells
      (Human osteosarcoma cell line) cultured in the BMG medium extracts for 1, 3 and 5
      days were determined by CCK-8 assay. The cellular morphology of MG-63 cells
      cultured on the surface of samples for 3 days was tested through laser scanning
      confocal microscopy (LSCM) and scanning electron microscopy (SEM). The relative
      growth rate (RGR) of MG-63 cells cultured in Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3 and
      pure Zr were both more than 85%, indicating that the cytotoxicity of BMG was
      relatively low and met the national biomedical material eligibility standard.
      There was insignificant difference in the morphology of MG-63 cells cultured in
      the BMG medium extracts and the control group through LSCM and SEM, which showed
      the BMG had excellent biological compatibility. The Zr-based bulk metallic glass
      Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3 and the conventional Ti6Al4V alloy both had no
      obvious cytotoxicity to MG-63 cells. These results provided evidence that the new
      Zr-based bulk metallic glass could be potential replacement material for the
      orthopedic surgical implant.

PMID- 26211259
TI  - [Controlled Release of Low Molecular Protein Insulin-like Growth Factor-1 through
      Self-Assembling Peptide Hydrogel with Biotin Sandwich Approach].
AB  - Since the release rate of protein in hydrogels is directly dependent upon the
      size of the protein and the hydrogel, how to deliver low molecular weight protein
      for prolonged periods has always been a problem. In this article, we present a
      usage of self-assembling peptide (P3) with the RGD epitope on its N terminus. The
      concentration of the released insulin-like growth factor 1 (IGF-1) was determined
      by UV-vis spectroscopy and the release kinetics suggested a notable reduction of
      the IGF-1 release rate. Cell entrapment experiments revealed that IGF-1 delivery
      by biotinylated nanofibers could promote the proliferation of the mouse
      chondrogenic ATDC5 cells when compared with cells embedded within nanofibers with
      untethered IGF-1.

PMID- 26211260
TI  - [Effects of Inhibiting Necroptosis on H9c2 Cardiomyocytes Injury Induced by
      Hypoxia/Reoxygenation].
AB  - The aim of this study is to construct specific shRNA expressing plasmids, and to
      observe their effects on H9c2 cardiomyocytes injury induced by
      hypoxia/reoxygenation (H/R). RIPK1 and RIPK3 are the key kinases mediating the
      process of necroptosis. Using recombinant DNA technology, we inserted the
      synthetic shRNA into pSUPER vector to construct RIPK1-shRNA or RIPK3-shRNA
      plasmid respectively. We transfected H9c2 cardiomyocytes with the two shRNA
      plasmids respectively, before we treated them with H/R stimulation. Then, we
      measured the relevant genes and proteins by real-time PCR and Western blot.
      Meanwhile,we detected the markers of necroptosis and cardiomyocytes injury. The
      results showed that inhibition of ripk1 or ripk3 gene expression by its specific
      shRNA might protect the cardiomyocytes injury induced by H/R stimulation.

PMID- 26211261
TI  - [Construction of Lentiviral Expression Vector Containing Extracellular Domain of
      Human Hepatocyte Growth Factor Receptor and Its Expression in 293T Cell].
AB  - This research aims to construct a lentiviral expression vector carrying the
      extracelluar domain (ED) of human hepatocyte growth factor receptor (C-Met), and
      to express it in transfected 293T cells. The extracellular domain of C-Met was
      amplified by RT-PCR, ligated with lentiviral expression vector p RRL-CMV-ED, and
      then expressed in 293T cell line. The expressed protein was purified and
      identified by RT-PCR and Western blot. The enzyme digestion and sequence analysis
      showed that the lentiviral expression vector p RRL-CMV-ED was constructed
      correctly. The size of amplified genes was about 2 700 bp. The purified protein
      with Ni-affinity column was about 105 kD analyzed by SDS-PAGE. The Western blot
      and ELISA results showed that the expressed protein which could bind to HGF
      specifically was the extracelluar domain of human hepatocyte growth factor
      receptor. This research may lay a foundation for further study of anti-C-MET
      monoclonal antibody and neutralizing antibody.

PMID- 26211262
TI  - [Research on Molecular Biological Characteristics of Proto-oncogene pim-2].
AB  - The purpose of this paper is to present the research on the molecular biological
      characteristics of proto-oncogene pim-2 and to analyze the related mechanism.
      Proto-oncogene pim-2 was studied and analyzed by the bioinformatics method and
      technology. With an online server, the chromosomal localization of pim-2 gene was
      analyzed, and the exon, open reading frame, CpG island and miRNAs complementary
      fragments and the like were predicted. With bioinformatics software, the
      physicochemical property of transcription protein of proto-oncogene pim-2 and
      various modification sites of protein sequence, such as ubiquitination and
      glycosylation, were predicted, the antigenic index was calculated, and the
      spatial structural was modeled. The research findings showed that the proto
      oncogene pim-2 comprised six exons, the CDS (coding sequence) transcribed a
      section of peptide chain including 311 amino acids, a gene promoter has a CpG
      island, and the 3'UTR region contains an miRNA gene. The molecular weight of the
      Pim-2 protein was 34,188. 47, the isoelectric point was 5.78, the instability
      index was 45.87, and the extinction coefficient was 279nm. A plurality of
      covalent modification sites, two ubiquitination sites, four glycosylation sites,
      an SUMO sumoylation site, a nitrosation site, two palmitoylation sites and
      sixteen regions with higher antigenic index were distributed in the protein
      sequence. This research showed that the related regions and modification sites
      distributed on the sequence of proto-oncogene pim-2 were closely related to the
      carcinogenic effect thereof.

PMID- 26211263
TI  - [Changes of Intestinal Mucosal Barrier and Intestinal Flora in Rats with Severe
      Acute Pancreatitis].
AB  - This paper is to explore changes of intestinal mucosal barrier, intestinal flora,
      and bacterial translocation in rats with severe acute pancreatitis (SAP). Twenty
      four male SD rats were randomly divided into the control group (n = 10) and the
      experimental group (n = 14). The model of severe acute pancreatitis of rats was
      induced by the method of injecting adversely 5% sodium taurocholate into the
      common biliary-pancreatic duct. All of the rats were killed after 24 hours and
      the level of the serum amylase and the plasma endotoxin was determined after
      that. The pathological changes of pancreas and small intestine were observed
      through hematoxylin-eosin staining (HE staining) and the abdominal viscera
      bacterial translocation rates were tested. With the method of real-time
      polymerase chain reaction (RT-PCR) the quantity of the intestinal flora was
      analyzed. In the control group, the level of Escherichia coli, Lactobacillus and
      Bifidobacterium were 2.08 +/- 1.29, 11.04 +/- 7.55 and 12.21 +/- 4.95,
      respectively. On the contrast, the level of Escherichia coli in the cecum
      contents was much higher (9.72 +/- 3.58, P < 0.01), while the Lactobacillus
      number was decreased significantly (0.67 +/- 0.34, P < 0.01), and the
      Bifidobacterium number was also decreased (4.59 +/- 3.42, P < 0.05) in the
      experimental group, so the ratio of Bifidobacterium/Escherichia coli was
      reversed. Besides, in the experimental group, the plasma endotoxin positive rates
      and the bacterial translocation rates were much higher (P < 0.01 or P < 0.05) and
      the pathology scores of pancreas and small intestines were also significantly
      higher (P < 0.01) than those in the control group. These results indicated that
      in severe acute pancreatitis rats, the intestinal mucosal barrier was severely
      damaged and the dysbacteriosis occurs in the intestinal canal. And these might
      relate to the occurrence and development of multiple organ infection.

PMID- 26211264
TI  - [Evaluation of Dual-source Computed Tomography Angiography from Patients of
      Congenital Heart Defects with Tetralogy of Fallot Associated with Cardiovascular
      Malformation].
AB  - The aim of this study was to clarify characteristics of cardiovascular
      malformation in patients associated with tetralogy of Fallot (TOF) by using dual
      source computed tomography (DSCT) angiography. We retrospectively analyzed DSCT
      angiography of 99 consecutive patients with TOF. In addition to typical CT
      features of TOF in all patients, the DSCT angiography showed 27 cases (27.27%) of
      atrial septal defect, 14 cases (14.14%) of patents ductus arteriosus, 11 cases
      (11.11%) of bicuspid pulmonary valve, 18 cases (18.18%) of congenital coronary
      artery malformation, 22 cases (22.22%) of right aortic arch, 12 cases (12.12%) of
      persistent left superior vena cava, 8 cases (8.08%) of retro-aortic innominate
      vein and 9 cases (9.09%) of pulmonary venous anomalous. DSCT is capable of
      displaying anatomical characteristics of cardiovascular malformation in patients
      with TOF.

PMID- 26211265
TI  - [Tremor Suppression on Multi-DoF Wrist Joint Based on Functional Electrical
      Stimulation: A Simulation Study].
AB  - An automatic control system was designed to suppress pathological tremor on wrist
      joint with two degrees of freedom (DoF) using functional electrical stimulation
      (FES). The tremor occurring in the wrist flexion-extension and adduction
      abduction was expected to be suppressed. A musculoskeletal model of wrist joint
      was developed to serve as the control plant, which covered four main muscles
      (extensor carpi radialis longus, extensor carpi ulnaris, flexor carpi radialis,
      and flexor carpi ulnaris). A second-order mechanical impedance model was used to
      describe the wrist skeletal dynamics. The core work was to design the controller
      and a hybrid control strategy was proposed, which combined inverse model based on
      feed forward control and linear quadratic regulator (LQR) optimal control.
      Performance of the system was tested under different input conditions (step
      signal, sinusoidal signal, and real data of a patient)., The results indicated
      that the proposed hybrid controller could attenuate over 94% of the tremor
      amplitude on multi-DoF wrist joint.

PMID- 26211266
TI  - [Preparation of Ti-O Film Deposited on the Surface of a New Type of Artificial
      Mechanical Heart Valve].
AB  - The rutile structure titanium oxide (Ti-O) film was prepared on the pure titanium
      material TA2 (99.999%) surface by the magnetic filter high vacuum arc deposition
      sputtering source. The method can not only maintain the material mechanical
      properties, but also improve the surface properties for better biocompatibility
      to accommodate the physiological environment. The preparation process of the Ti-O
      film was as follows. Firstly, argon ions sputtered to the TA2 substrate surface
      to remove the excess impurities. Secondly, a metal ion source generated Ti ions
      and oxygen ions by the RF discharge. Meanwhile a certain negative bias was
      imposed on the sample. There a certain composition of Ti-O film was obtained
      under a certain pressure of oxygen in the vacuum chamber. Finally, X-ray
      diffraction was used to research the structure and composition of the film. The
      results showed that the Ti-O film of the rutile crystal structure was formed
      under the 0.18 Pa oxygen partial pressure. A Nano scratch experiment was used to
      test the coating adhesion property, which demonstrated that the film was stable
      and durable. The contact angle experiment and the platelet clotting experiment
      proved that the modified surface method had improved platelet adhesion
      performance, and, therefore, the material possessed better biocompatibility. On
      the whole, the evaluations proved the modified material had excellent
      performance.

PMID- 26211267
TI  - [Study on the Evaluation Index of Depth of Anesthesia Awareness Based on Sample
      Entropy and Decision Tree].
AB  - Currently, monitoring system of awareness of the depth of anesthesia has been
      more and more widely used in clinical practices. The intelligent evaluation
      algorithm is the key technology of this type of equipment. On the basis of
      studies about changes of electroencephalography (EEG) features during anesthesia,
      a discussion about how to select reasonable EEG parameters and classification
      algorithm to monitor the depth of anesthesia has taken place. A scheme which
      combines time domain analysis, frequency domain analysis and the variability of
      EEG and decision tree as classifier and least squares to compute Depth of
      anesthesia Index (DOAI) is proposed in this paper. Using the EEG of 40 patients
      who underwent general anesthesia with propofol, and the classification and the
      score of the EEG annotated by anesthesiologist, we verified this scheme with
      experiments. Classification and scoring was based on a combination of modified
      observer assessment of alertness/sedation (MOAA/S), and the changes of EEG
      parameters of patients during anesthesia. Then we used the BIS index to testify
      the validation of the DOAI. Results showed that Pearson's correlation coefficient
      between the DOAI and the BIS over the test set was 0.89. It is demonstrated that
      the method is feasible and has good accuracy.

PMID- 26211268
TI  - [Constitution of a Real-time Monitoring System of Cerebral Hemorrhage with
      Magnetic Induction].
AB  - The real-time monitoring of cerebral hemorrhage can reduce its disability and
      fatality rates greatly. On the basis of magnetic induction phase shift, we in
      this study used filter and amplifier hardware module, NI-PXI data-acquisition
      system and LabVIEW software to set up an experiment system. We used Band-pass
      sample method and correlation phase demodulation algorithm in the system. In
      order to test and evaluate the performance of the system, we carried out saline
      simulation experiments of brain hemorrhage. We also carried out rabbit cerebral
      hemorrhage experiments. The results of both saline simulation and animal
      experiments suggested that our monitoring system had a high phase detection
      precision, and it needed only about 0.030 4s to finish a single phase shift
      measurement, and the change of phase shift was directly proportional to the
      volume of saline or blood. The experimental results were consistent with theory.
      As a result, this system has the ability of real-time monitoring the progression
      of cerebral hemorrhage precisely, with many distinguished features, such as low
      cost, high phase detection precision, high sensitivity of response so that it has
      showed a good application prospect.

PMID- 26211269
TI  - [An Algorithm for Microcirculatory Blood Flow Velocity Measurement Based on Trace
      Orientation in Spatiotemporal Image].
AB  - The velocity of blood in vessels is an important indicator that reflects the
      microcirculatory status. The core of the measurement technology, which is based
      on spatiotemporal (ST) image, is to map the cell motion trace to the two
      dimensional ST image, and transfer the measurement of flow velocity to the
      detection of trace orientation in ST image. This paper proposes a trace
      orientation measurement algorithm is based on Randomized Hough Transformation and
      projection transformation, and it is able to estimate trace orientation and flow
      velocity in noisy ST images. Experiments showed that the agreement between the
      results by manual and by the proposed algorithm reached over 90%.

PMID- 26211270
TI  - [A Feature Extraction Method for Brain Computer Interface Based on Multivariate
      Empirical Mode Decomposition].
AB  - This paper presents a feature extraction method based on multivariate empirical
      mode decomposition (MEMD) combining with the power spectrum feature, and the
      method aims at the non-stationary electroencephalogram (EEG) or
      magnetoencephalogram (MEG) signal in brain-computer interface (BCI) system.
      Firstly, we utilized MEMD algorithm to decompose multichannel brain signals into
      a series of multiple intrinsic mode function (IMF), which was proximate
      stationary and with multi-scale. Then we extracted and reduced the power
      characteristic from each IMF to a lower dimensions using principal component
      analysis (PCA). Finally, we classified the motor imagery tasks by linear
      discriminant analysis classifier. The experimental verification showed that the
      correct recognition rates of the two-class and four-class tasks of the BCI
      competition III and competition IV reached 92.0% and 46.2%, respectively, which
      were superior to the winner of the BCI competition. The experimental proved that
      the proposed method was reasonably effective and stable and it would provide a
      new way for feature extraction.

PMID- 26211271
TI  - [Development of a Surgical Navigation System with Beam Split and Fusion of the
      Visible and Near-Infrared Fluorescence].
AB  - This paper presents a surgical optical navigation system with non-invasive, real
      time, and positioning characteristics for open surgical procedure. The design was
      based on the principle of near-infrared fluorescence molecular imaging. The in
      vivo fluorescence excitation technology, multi-channel spectral camera technology
      and image fusion software technology were used. Visible and near-infrared light
      ring LED excitation source, multi-channel band pass filters, spectral camera 2
      CCD optical sensor technology and computer systems were integrated, and, as a
      result, a new surgical optical navigation system was successfully developed. When
      the near-infrared fluorescence was injected, the system could display anatomical
      images of the tissue surface and near-infrared fluorescent functional images of
      surgical field simultaneously. The system can identify the lymphatic vessels,
      lymph node, tumor edge which doctor cannot find out with naked eye intra
      operatively. Our research will guide effectively the surgeon to remove the tumor
      tissue to improve significantly the success rate of surgery. The technologies
      have obtained a national patent, with patent No. ZI. 2011 1 0292374. 1.

PMID- 26211272
TI  - [18F-Berberine Derivatives: a Potential Molecular Imaging Agent for Tumor
      Targeting by PET/CT Tumor].
AB  - Cancer is one of the main causes of death for human beings. Clinical oncologists
      increasingly rely upon imaging for diagnosis, stage, response assessment, and
      follow-up in cancer patient. However, 18F-FDG is not a tumor specific agent,
      inflammation and infection also have intensive uptake of 18F-FDG, resulting in
      false positive diagnosis, and some tumors have low uptake of 18F-FDG or even do
      not uptake 18F-FDG, leading to false negative diagnosis. So it is urgent to
      develop non-18F-FDG novel tumor targeting agent. Recently, a large number of
      researches in vitro have demonstrated that berberine has anti-tumor activity
      against a variety of tumor cells by inducing tumor cell apoptosis through
      inhibition of mitochondrial respiratory chain etc. So far, there is no credible
      evidence of berberine targeting in tumor in vivo. We proposed a hypothesis that
      berberine has the characteristics of tumor targeting biodistribution in vivo, and
      verified the proposal by 18F-berberine PET/CT imaging in VX2 muscle tumor-bearing
      rabbit model. In this review, we intend to give an overview of the progress of
      berberine anticancer, the structural bases of berberine anticancer and the
      uderlying molecular mechanisms of berberine anticancer indentified so far. We
      also introduce the first visualization of 18F labeled berberine derivatives
      targeting tumor in VX2 muscle tumor-bearing rabbit model by PET/CT. These
      breakthrough findings suggest that 18F-berberine derivatives as a potential
      PET/CT tumor targeted molecular imaging agent may have important implications for
      cancer targeting therapy, molecular imaging and modernization of Traditional
      Chinese Medicine.

PMID- 26211273
TI  - [Research Progress in Preparation of Antimicrobial Peptides and Their Mechanisms
      of Action].
AB  - Currently, all the conventional antibiotics have developed corresponding drug
      resistant pathogenic strains, which have increasingly become a serious threat to
      people's health. Development of completely new types of antibiotics is one of
      effective ways to solve the drug resistance issue. Antimicrobial peptides with
      broad-spectrum antibacterial and antimicrobial activity and wild variety become
      the ideal alternative to traditional antibiotics. Antimicrobial peptides are
      derived from wide range of sources, such as plants, animals, and microorganisms.
      Mechanism of function of the antimicrobial peptides and the investigation
      approaches of different antimicrobial peptides also vary dramatically. In this
      paper, we give an overview of preparation, antibacterial mechanisms, and research
      methodology of antimicrobial peptides.

PMID- 26211274
TI  - [Research Progress in Seeding Cells of Peripheral Nerve].
AB  - Seeding cells play an important role in the peripheral nerve damage repair.
      Seeding cells studied conse- quently in peripheral nerve are Schwann cells, bone
      marrow mesenchymal stem cells and neural stem cells. Schwann cells, the first
      seeding cells, are various unique glial cells in the peripheral nervous system,
      which can form the myelin sheath for insulation and package of the neuron
      projecting axons in the peripheral nervous system so that the conduction velocity
      of the nerve signal was accelerated. It can be proved that Schwann cells played
      an important role in the maintenance of peripheral nerve function and in the
      regeneration process after peripheral nerve injury. The second, bone marrow
      mesenchymal stem cells are the various mesenchymal stem cells mainly exist in the
      systemic connective tissues and organs. These functional stem cells are often
      studied at present, and it has been found that they have exuberant proliferation
      and differentiation potentials. Neural stem cells, mentioned the third in
      sequence, are the kind of pluripotent cells with multi-directional
      differentiation, which could conduct the self-renewal function, and generate and
      differentiate neurons, astrocytes and oligodendrocytes through asymmetric cell
      division. These three types of seed cells are discussed in this paper.

PMID- 26211275
TI  - [Advances of Research on Ataxia Telangiectasia Mutated Gene and Risk Factors of
      Cardiovascular Disease].
AB  - Cardiovascular disease is a severe threat to human health and life. Among many
      risk factors of cardiovascular disease, genetic or gene-based ones are drawing
      more and more attention in recent years. Accumulated evidence has demonstrated
      that the loss or mutation of ataxia telangiectasia mutated (ATM) gene can result
      in DNA damage repair dysfunctions, telomere shortening, decreased antioxidant
      capacity, insulin resistance, increased lipid levels, etc., and thus can promote
      the occurrence of cardiovascular risk factors, such as aging, atherosclerosis and
      metabolic syndrome. In this review, we discusses the possible mechanisms between
      ATM gene and cardiovascular risk factors, which could be helpful to the related
      research and clinical application.

PMID- 26211276
TI  - [Influencing Factors on the Properties of Bone Scaffolds and Their Manufacturing
      Techniques].
AB  - To serve as carriers of cells and bioactive molecules, three-dimensional
      scaffolds play a key role in bone defect repair. The chemical component and
      microstructure of the scaffold can affect the mechanical properties and seed
      cells. A variety of fabrication techniques have been used in producing scaffolds,
      some made random porous structure, some created well-designed structure using
      rapid prototyping methods, and others prepared bio-derived materials as
      scaffolds. However, scaffolds may vary in their inner structure, mechanical
      properties and repairing efficiency as well because of different manufacturing
      methods. In this review, we overview the main achievements concerning the effects
      of material and microstructure on the mechanical performance, seed cells and
      defect repair of bone scaffolds.

PMID- 26211277
TI  - [Additive Manufacturing and Its Medical Applications].
AB  - Additive manufacturing (AM) is a collection of technologies based on the layer-by
      layer manufacturing. Characterized by its direct manufacturing and rapidity, it
      has been regarded by the Economist Journal as one of the key techniques which
      will trigger the third industry reformation. The present article, beginning with
      a brief introduction of the history of AM and the process of its major
      technologies, focuses on the advantages and disadvantages and medical
      applications of the technique.

PMID- 26211278
TI  - [Research Progress in Genotoxic Effects of Degradation Products, Cobalt, Chromium
      Ions and Nanoparticles from Metal-on-metal Prostheses on Cells].
AB  - Cobalt or chromium alloys are the most common clinical materials of prosthesis
      and there have been some investigators at home and abroad have done related
      researches about the genotoxic effects of cobalt and chromium ions and
      nanoparticles. People have certain understanding about the mechanism of
      production of ions as well as their influence on cells. However, chromium or
      cobalt nanoparticles genotoxicity related research is still in its preliminary
      stage. In each stage, the mechanisms, from creating of the particles, through
      entering cells, until finally causing genotoxic, are still contained many
      problems to be solved. This article reviews the research progress in mechanisms
      of production and genotoxic effects of cobalt, chromium ions and nanoparticles.

PMID- 26211279
TI  - [Influence Factors on Monomer Conversion of Dental Composite Resin].
AB  - Dental composite resin is a kind of material which has been widely used in dental
      restoration. Research has found that the influence of residual monomer on the
      material mechanical, chemical and biological properties cannot be ignored. This
      paper elaborates these harms of residual monomers. The effects of resin matrix,
      inorganic filler and initiating system, illumination, secondarily treatment on
      the degree of conversion were also analyzed. The paper also discusses the
      effective measures to increase the conversion, and offers theoretical basis for
      the clinical application and development of composite resin.

PMID- 26211280
TI  - [Diabetes in 2015: constantly increasing, but with enlarged therapeutics
      options].

PMID- 26211281
TI  - [Metformin: new data for an old molecule].
AB  - Metformin is the first-line oral agent for the treatment of type 2 diabetes
      according to the guidelines. Metformin decreases hepatic glucose production, does
      not induce weight gain and does not increase the risk of hypoglycemia. However,
      decades after its introduction, its mode of action has been only recently
      highlighted. The side effects of metformin are well known and consist primarily
      of digestive problems. Although rare, the dreaded complication is lactic
      acidosis, which can develop in patients with severe renal insufficiency or in
      conditions of low perfusion. The purpose of this article is to review the
      indications, risks and benefits of this drug, but also to discuss new evidence
      related to its mechanism of action and the conditions that increase the risk of
      lactic acidosis.

PMID- 26211282
TI  - [GLP-1 receptor agonists versus SGLT-2 inhibitors in obese type 2 diabetes
      patients].
AB  - Who never had a type 2 obese diabetic patient, treated by several oral
      antidiabetic drugs and insulin, with consequent weight gain associated with the
      therapeutic escalation and uncontrolled diabetes? The arrival of GLP-1 agonists
      and SGLT-2 inhibitors allows to reevaluate the management of these patients, with
      their favorable effects on glycemic control, weight and the risk of hypoglycemia
      and their complementary mechanisms to conventional treatments. The vicious cycle
      of weight gain and increased need of insulin is limited. The choice between these
      two molecules must be based on several factors (glycemic target, weight,
      comorbidities, route of administration, side effects, etc.), and the balanced
      enthusiasm of these new treatments with the insufficient data regarding their
      long-term safety and their impact on micro- and macrovascular complications.

PMID- 26211283
TI  - [Classification of diabetes: an increasing heterogeneity].
AB  - Diabetes mellitus is usually subdivided into type 1 and type 2. Despite precise
      criteria, distinction between these two types of diabetes can be difficult
      because of cases with superposition of the two classes. Adults aged 20 to 40 are
      particularly at risk of presenting an intermediary type of diabetes and thus are
      subject to misclassification. The distinction between these subtypes is relevant
      because of the therapeutic decision and the outcome which relies on insulin
      supply and therefore the evolution to insulin dependence. Thus, it seems
      important to review a new and more accurate classification of diabetes to offer a
      more appropriated care to patients.

PMID- 26211284
TI  - [The infected diabetic foot: diagnosis and management].
AB  - Foot infections are a frequent and potentially harmful complication of diabetes
      mellitus. In one skin ulceration out of two, further evolution towards infection
      occurs and often leads to amputation increasing morbidity and health care costs.
      Skin disruptions, favored by the sensorimotor neuropathy and vascular disease,
      constitute the initial factors leading to this complication. To ensure effective
      care, these cases must be managed by a multidisciplinary team in a specialized
      center. All caretakers involved with patients suffering from diabetes mellitus
      must be capable of preventing and recognizing diabetic foot infections, as well
      as informing the patients about this complication and its management.

PMID- 26211285
TI  - [Polycystic ovaries: what's news in 2015?].
AB  - Polycystic ovary syndrome is a very common endocrine disorder in women of
      reproductive age, with important clinical implications (fertility issues,
      hirsutism, metabolic abnormalities). The Endocrine society has published in 2013
      a series of diagnostic and treatment recommendations, followed by the European
      society of endocrinology in 2014. Recently, advances have been made in the
      measure of androgen biomarker and the evaluation of ovarian morphology with 3D
      ultrasound techniques. New treatments have emerged for fertility problems
      associated with the syndrome (ex. letrozole).

PMID- 26211286
TI  - [Artificial sweeteners and diabetes: friends or foes?].
AB  - Sugary drinks consumption is associated with increased risk of obesity and type 2
      diabetes. Thereby, artificial sweeteners (AS) consumption became increasingly
      popular and were introduced largely in our diet in order to reduce calorie intake
      and normalise blood glucose levels without altering our taste for "sweetness".
      However, the results of published studies on health outcomes secondary to AS
      intake, including type 2 diabetes risk, are inconsistent. The aim of this article
      is to focus on the role of AS in glucose homeostasis and diabetes onset.

PMID- 26211287
TI  - [Scapholunate lesions and instabilities--how to recognize and treat them?].
AB  - The lesions of the scapholunate ligament are some of the most frequently
      encountered in the wrist. Left untreated, the complete rupture of the ligament is
      followed by degenerative arthritis according to a well-defined pattern of
      progression through the wrist, eventually leading to multifocal arthrosis, a
      condition described as scapholunate advanced collapse (SLAC wrist). The
      scapholunate lesions are classified in stages according to the degree of the
      lesion established by imaging studies or arthroscopy and to the chronicity of the
      lesion. Both together essentially determine the healing potential and the
      prognosis, which rapidly decrease after six weeks from the initial trauma, thus
      indicating the importance of recognizing the acute or subacute lesion and
      directing the patient to the hand surgeon early enough. The therapeutic options
      are notably reduced and often of palliative nature in case of chronic lesions
      with secondary changes in the wrist mechanics or cartilage damage.

PMID- 26211288
TI  - [Zona vaccine, molecular screening of lung cancer].

PMID- 26211289
TI  - [A dramatic drone].

PMID- 26211290
TI  - ["Alexia without agraphia? So, it was the calcarine sulcus!"].

PMID- 26211291
TI  - [The traveler's diarrhea: resist taking antibiotics!].

PMID- 26211292
TI  - [Evolution and changes of family planning].

PMID- 26211293
TI  - [Highly specialized medicine: report from Peter Suter].

PMID- 26211294
TI  - [Immortality, death and other minor phenomena].

PMID- 26211296
TI  - Citation Oversight.

PMID- 26211295
TI  - What's the Impact of Religion at the Bedside?

PMID- 26211297
TI  - Spiritual Gifts in Nursing.

PMID- 26211298
TI  - NP Collaborative Practice and Servant Leadership.

PMID- 26211299
TI  - Moral Distress--New Way of Looking at an Old Problem?

PMID- 26211300
TI  - Older African Americans' Beliefs about Pain, Biomedicine, and Spiritual Medicine.
AB  - Persistent (chronic) pain prompts older African Americans (AAs) to utilize a
      combination of biomedicine (BM) and spiritual medicine (SM)for pain management.
      Because less is known about how older AAs use these pain management
      interventions, healthcare providers are unable to provide holistic care and
      optimal pain management. Using a Christian and Afrocentric perspective, this
      article reviews older AAs use of BM and SM, offering reconmendations on how to
      integrate BM and SM for pain management.

PMID- 26211301
TI  - DEFINING HOPE AMONG HIV-Positive AFRICAN AMERICAN FEMALES.
AB  - Human immunodeficiency virus (HIV) affects heterosexual African American females
      (AAFs) with morbidity and mortality rates higher than females of any other race,
      accounting for thefourth largest number of HIV infections in the United States.
      Defining hope is importantfor understanding and therapeutic use of the concept in
      AAFs with HITA literature review exploring uses for this concept among HIV
      positive AAFs, and a dimensional analysis, revealed positive and negative
      influences for hope. Tuthful and positive messages need to be developed for this
      population.

PMID- 26211302
TI  - SERVICE-LEARNING AND INTERPROFESSIONAL EDUCATION IN NURSING: A Critical Need.
AB  - Service-learning and interprofessional education can have an effect on nursing
      students' learning experiences, attitudes, transcultural knowledge, and on
      patient outcomes. Interprofessional education is a method in which healthcare
      students learn their different roles and responsibilities, and recognize how
      patients benefit from the collaborative process. The purpose of this paper is to
      review professional literature to determine the best practices for implementation
      of service-learning and interprofessional education into nursing curricula.

PMID- 26211303
TI  - USING THE Internet TO INCREASE Physical Activity IN A FAITH COMMUNITY.
AB  - Physical inactivity is the biggest public health problem of the 21st Century.
      Additionally, minority populations have higher rates of obesity and obesity
      related illnesses, supporting the need to develop culturally-appropriate physical
      activity interventions for these populations. For African Americans (AAs),
      churches promote spiritual, mental, and physical well-being. The Internet offers
      an innovative medium to produce health behavior change and may be ideal to use
      with AAs in a church setting. A simple, no-cost, 8-week, Internet-delivered
      intervention to increase physical activity was piloted in an AA church. Level of
      activity increased, whereas time spent sitting decreased.

PMID- 26211304
TI  - Practical Health Promotion: Weekly Health Tips for the Faith Community.
AB  - Evidence supports that people with higher levels of health literacy report higher
      levels of wellness. Using the weekly worship service of the faith community as a
      way to distribute health information is an ideal way to promote congregational
      knowledge of health issues. this article discusses using the printed church
      bulletin and other weekly church communications to disseminate parish health tips
      (PHTs), provides resources for developing PHT, and offers 52 PHT's.

PMID- 26211305
TI  - What GUIDES Your NURSING PRACTICE?
AB  - Nurses' personal belief systems or philosophies about nursing and people guides
      their nursing care, especially in difficult situations. Defining and articulating
      a personal philosophy helps the nurse better understand the motivation and
      reasoning behind his or her work. In this article, a nurse shares her philosophy
      of nursing, underlying beliefs, and discusses how this guides her practice.
      Questions to help nurses articulate their own personal philosophy of nursing are
      included.

PMID- 26211306
TI  - The Call to Excellence--No Room for Complacency.
AB  - The call of the nurse is to promote, protect, and support health in all areas of
      life. Christian nurses are further called to imitate Jesus Christ. Yet,
      complacency is a common attitude among nurses. With new national standards of
      collecting and publicly reporting patient perceptions of care, positive nursing
      attitudes and excellent care are imperative to successful outcomes. What does it
      mean to seek professional excellence?

PMID- 26211307
TI  - How Can Nurses Be Healers?

PMID- 26211308
TI  - Vocation of Faith: The Influence of Mother Teresa on Christian Nursing, Part 2.

PMID- 26211309
TI  - Calling Others to Teach.

PMID- 26211310
TI  - Good Stewardship Means Good Business.

PMID- 26211311
TI  - [Research progress of microbial haloalkane dehalogenase--a review].
AB  - Haloalkane dehalogenases are key enzymes for biodegradation of halogenated
      aliphatic compounds, widely distributed in various microbial species of wide
      geographical distributions, and of significance in practical application such as
      bioremediation and industrial biocatalysis. Twenty haloalkane dehalogenases have
      been biochemically characterized so far. In recent years, progresses have been
      made in the enzymatic characteristics, protein structures, and phylogenetic
      diversity. We reviewed the progresses of haloalkane dehalogenase in structure and
      function, diversity and application potential.

PMID- 26211312
TI  - [Lytic phages and prophages of Streptococcus suis--a review].
AB  - Streptococcus suis (S. suis) is an important zoonosis and pathogen that can carry
      prophages. In this review, we focus on the recent advances in our understanding
      of lytic phage and lysogenic phage of S. suis, including the morphology of S.
      suis lytic phage, the functions of lysin and terminase large subunit encoded by
      S. suis lytic phage, comparative genomics of S. suis prophages, lysogenic.
      conversion between S. suis lytic phage and prophage. Furthermore, prospective
      evolution of interactions between phage and host was discussed.

PMID- 26211313
TI  - [Advances in baculovirus per os infection and per os infectivity factor--A
      review].
AB  - Baculoviruses are a family of arthropod-specific viruses that mainly affect
      insects of the orders Lepidoptera, Hymenoptera, and Diptera. In nature,
      baculoviruses establish infection in their hosts orally and a battery of proteins
      designated as per os infectivity factors play pivotal roles in baculovirus per os
      infection. This review summarizes the basic characteristics of baculovirus and
      discusses the main events that baculovirus establishes per os infection,
      including the evolutionary advantages for baculovirus to initiate infection
      through the oral route, the binding and fusion of baculovirus virions with insect
      midgut microvilli and the functional roles of baculovirus per os infectivity
      factors. These achievements and advances should promise to shed light on the
      understanding and utilization of baculovirus for bio-control and exogenous gene
      expression in the future.

PMID- 26211314
TI  - [Isolation, identification and characterization of rice rhizobacterium
      Pseudomonas aeruginosa PA1201 producing high level of biopesticide "Shenqinmycin"
      and phenazine-1-carboxamide].
AB  - OBJECTIVE: To identify bacterial strains with the inhibitory activity to rice
      pathogens, and to evaluate their potentials for the development of new
      biopesticides. METHODS: Rice rhizosphere Pseudomonas strains were isolated using
      1-aminocyclopropane-1-carboxylic acid as the sole carbon source. Strain PA1201
      was further identified through morphological analysis, biochemical
      characterization, 16S rDNA sequence analysis and phospholipid fatty acid
      profiling. Qualitative and quantitative analysis of the production of the green
      pesticide Shenqinmycin as well as phenazine-1-carboxamide produced by PA1201 was
      done by HPLC. Cytotoxicity of PA1201 was evaluated using human alveolar
      epithelial cell line A549 and Drosophila melanogaster as hosts. RESULTS: Strain
      PA1201 inhibited Rhizotonia solani Kuhn and Xanthomonas oryzae pv. oryzae, the
      causal agents of rice sheath blight and bacterial blight, respectively. It was
      further identified as Pseudomonas aeruginosa PA1201, which produces shenqinmycin
      and phenazine-1-carboxamide. The fermentation titer of shenqinmycin and phenazine
      1-carboxamide in the PPM medium was 81.7 mg/L and 18. 1 mg/L, respectively. In
      the medium supplemented with soybean meal and corn steep liquor, the level of
      shenqinmycin and phenazine-1-carboxamide reached 926. 9 mg/L and 489. 5 mg/L.
      PA1201 also produced high level of extracellular protease and was toxic to human
      cell line and fruit fly. CONCLUSION: Strain PA1201 could be engineered for higher
      yield of Shenqinmycin or for a new biopesticide.

PMID- 26211315
TI  - [Microbial diversity of salt lakes in Badain Jaran desert].
AB  - OBJECTIVE: We characterized procaryotic biodiversity, community structure and the
      relationship between the community structure and environmental factors of salt
      lakes in Badain Jaran desert, Inner Mongolia, China. METHODS: We constructed 16S
      rRNA gene clone libraries by molecular biology techniques to analyze the
      procaryotic phylogenetic relationships, and used R language to compare the
      community structure of haloalkalophiles in the salt lakes. RESULTS: Water in this
      region has a high salinity ranging from 165 to 397 g/L. The water is strongly
      alkaline with pH value above 10. The microbial diversity and community structure
      of the salt lakes are obviously different. The diversity of bacteria is more
      abundant than that of archaea. The main categories of bacteria in the samples are
      Gammaproteobacteria, Bacteroidetes, Alphaproteobacteria, Firmicute and
      Verrucomicrobia, whereas all archaea only belong to Halobacteriaceae of
      Euryarchaeota. CONCLUSION: Salinity is the most important environmental factor
      influencing the bacterial community structure, whereas the archaea community
      structure was influenced comprehensively by multiple environmental factors.

PMID- 26211316
TI  - [Identification of a fungal isolate causing adzuki bean rust in Heilongjiang].
AB  - OBJECTIVE: The aim of the study is to identify the pathogen causing adzuki bean
      (Phaseolus angularis) rust in Daqing, Heilongjiang province. METHODS: Adzuki bean
      rust leaves were collected from Daqing, Heilongjiang province, China. A pure
      culture of rust isolate ZXL01 was obtained by single pustule isolation. Its
      taxonomic status was determined by observing the number of germ pores of
      urediniospores, germ pore location and the wall thickness of teliopores, and
      sequencing ribosomal DNA internal transcribed spacer (rDNA-ITS). RESULTS:
      Morphological studies showed that most of the urediospores of ZXL01 had two germ
      pores that were far from spores' equator area. The wall thickness of teliopores
      ranged from 2.9 to 3. 3 microm. The rDNA-ITS sequence of ZXL01 was clustered in
      one clade with 2 reference isolates of Uromyces vignae (GenBank accession numbers
      AB115718 and AB115731) at 99% bootstrap levels in the phylogenetic tree. A 500 bp
      amplified product was obtained by the specific primers UV-ITSF/R, which was
      specific for U. Vignae. CONCLUSION: The morphological features and ITS analysis
      indicated that the rust fungus ZXL01 occurred on leaves of adzuki bean in Daqing
      was U. Vignae, and the accession number of GenBank was KM461700.

PMID- 26211317
TI  - [Construction and characterization of Listeria monocytogenes deltahfq mutant
      strain].
AB  - OBJECTIVE: Gram-positive brevibacterium Listeria monocytogenes (Lm) is an
      important zoonotic foodborne pathogen, engaged in both saprophytism and
      parasitism. It could adapt, survive and display pathogenicity under different
      environmental stress challenges, which is associated with the regulatory network
      consisting of regulating factors. The biological characterizations of regulator
      hfq was evaluated in this study. METHODS: hfq deleted serovar 1/2 a strain EGDe
      was constructed with homologous recombination, the biological characteristics of
      the mutant strain was compared with its parental strain. RESULTS: The growth of
      EGDe delta hfq was significantly inhibited under cold temperature (P < 0.05),
      salt medium containing 7% NaCl and the medium containing 4.5% ethanol. The
      ability of biofilm formation of the mutant strain in BactoTM Brain Heart Infusion
      (BHI) was reduced significantly (P < 0.05); notably, the invasion rate to Caco-2
      cell lines was obviously reduced. Infection capacity of EGDe delta hfq to BALB /c
      mice decreased and the LDD was 6 times higher than EGDe. CONCLUSION: Hfq protein
      of Listeria monocytogenes plays an important role in regulating bacterial
      virulence, biofilm formation and stress response. This deletion strain provided
      material to further study the function of Hfq and provides the possibilities to
      elucidate the mechanisms of Lm in resisting the stress and paves ways to the
      development of novel strategies for the prevention and control of Lm infections.

PMID- 26211318
TI  - [Effect of 6-phosphofructokinase gene-pfk overexpression on nisin production in
      Lactococcus lactis N8].
AB  - OBJECTIVE: To accelerate the formation of nisin through overexpressing 6
      phosphofructokinase gene pfk in nisin-producer Lactococcus lactis N8. METHODS:
      The genes of pfk and pkaC encoding the catalytic subunit of cAMP-dependent
      protein kinase were cloned into the vector pMG36e andtransformed into L. lactis
      N8, resulting in the recombinant strain L. lactis N8-pMG36e-pfk-pkaC. Several
      biochemical and physological factors, including growth profiles, activity of 6
      phosphofructokinase, expression of nisA , antibacterial activity of supernatants
      and nisin titer, were monitored to investigate the differences between the
      recombinant strain and the parental strain. RESULTS: No significant difference
      was observed with respect to the growth patterns of the recombinant strain and
      the wild type. As expected, the biological activity of PFK in recombinant strain
      was increased for all examined samples. Correspondingly, the yield of nisin was
      increased by 20% in the recombinant strain after fermentation for 10 hours, which
      could be attributed to the accelerated biosynthesis of nisin. As a result, the
      fermentation cycle was reduced about 2 hours. Meanwhile, different concentration
      of glucose did not affect the formation of nisin. CONCLUSION: The overexpression
      of pfk and pkaC genes in the nisin-producer strain can effectively accelerate
      nisin biosynthesis.

PMID- 26211319
TI  - [Physiological and biochemical characteristics of a manganese catalase lacking n
      terminal].
AB  - OBJECTIVE: We characterizeda manganese catalase lacking n-terminal ( MnCAT-C), to
      revealits roles in bacterial growth, reactive oxygen species ( ROS) removal and
      degradation of polychlorinated biphenyls ( PCBs) in Rhodococcus sp. R04. METHODS:
      Manganese catalase (Mn-CAT) sequence of the strain R04 was aligned with that of
      Rhodococcus sp. R11101. Mn-CAT and MnCAT-C were expressed in E. coli BL21 (DE3),
      and the target protein was purified with Q-sepharose and ammonium sulphate
      precipitation. Knockout strain was obtained by homologous recombination. ROS was
      measured by fluorescence polarization, and the degradation rate of PCBs was
      measured by HPLC. [Results] MnCAT-C protein was purified, and SDS-PAGE analysis
      showed that its molecular weight was 23 kDa. Compared with wild strains, the ROS
      concentration increased, and the growth rate was inhibited in knockout strains.
      Moreover, the degradationrate of PCBs decreased. [Conclusion] MnCAT-C retained
      the majority of the active properties of the original enzyme, including ROS
      clearance. The lack of MnCAT-C gene affected the growth rate and the
      PCBsdegradationrate instrain R04.

PMID- 26211320
TI  - [Accumulation of antibiotics, heavy metals and antimicrobial-resistant bacteria
      in duck bio-bed].
AB  - OBJECTIVE: The objective of this study is to understand the accumulation of
      antibiotics, metals in the litter, and evolution features of bacterial
      antimicrobial-resistance during the fermentation of duck bio-bed. METHODS: The
      experiment was conducted in meat duck bio-bed farm of Jiangsu province from
      November 2011 to July 2013. The new litter and spent litter from 4th, 8th meat
      duck flock were studied for the accumulation of consumed antimicrobials and
      metals. Bacterial resistance levels to consumed antimicrobials were measured in
      the collected litter. RESULTS: The residues of doxycycline in the litter
      increased significantly after successive flocks of meat ducks, but ofloxacin had
      not been detected in all litter samples. The litter for the 8th meat duck flock
      had the highest level of resistant cultivable bacteria in the three sorts of
      medium amended with 16 microg/mL, 100 microg/mL doxycycline. Meanwhile, the level
      of resistant cultivable bacteria in the same sort of medium amended with 8
      microg/mL, 50 microg/mL ofloxacin differed insignificantly between different
      flock litter sample. Different flock litter differed insignificantly in the
      accumulation content of As, Pb and Hg, and was low in Cd. The 4th, 8th flock
      litter increased significantly in Zn and Mn than new litter, and increased slowly
      in Cu and Cr. CONCLUSION: With the application of doxycycline in each flock of
      meat ducks, the content of doxycycline and doxycycline resistance in
      enterobacteriaceae bacteria in the litter increased significantly, Zn and Mn had
      an increasing trend overall.

PMID- 26211321
TI  - [Expression and characterization of a neutral Enterobacter cloacae GX-3
      invertase].
AB  - OBJECTIVE: To characterize a neutral invertase from Enterobacter cloacae GX-3.
      METHODS: By searching GenBank database, we found the genes encoding invertase
      from the same genus Enterobacter. These sequences were aligned and analyzed.
      Then, a gene encoding neutral invertase was amplified by PCR. The recombinant
      plasmid pQE-Einv was constructed. We purified the expressed protein Einv with
      nickel-nitrilotriacetic acid chromatography. At last, the characterics of the
      recombinant protein Einv were studied in detail. RESULTS: A gene encoding neutral
      invertase was discovered and cloned from E. cloacae GX-3. The recombinant enzyme
      Einv was characterized. Einv had an optimum pH of 6.5 and an optimum temperature
      of 40 degrees C. The results of sodium dodecyl sulfate polyacrylamide gel
      electropheresis (SDS-PAGE) and gel permeation chromatography ( GPC) showed that
      Einv was a homo-dimer protein. Einv retained 80% activity at sucrose
      concentrations up to 1170 mmol/L. But, Einv had no transglycosylation activity at
      high sucrose concentration. It could hydrolyze raffinose, 1-kestose, nystose,
      fructofuranosylnystose and stachyose. CONCLUSION: It is first reported that an
      invertase from Enterobacter cloacae is a beta-fructofuranosidase at neutral pH
      range. It only has hydrolysis activity without tranglycosylation activity. These
      characteristics indicate that the neutral invertase Einv has important
      applications in food industry.

PMID- 26211322
TI  - [Detection of CRISPR and its relationship to drug resistance in Shigella].
AB  - OBJECTIVE: To detect clustered regularly interspaced short palindromic repeats
      (CRISPR) in Shigella, and to analyze its relationship to drug resistance.
      METHODS: Four pairs of primers were used for the detection of convincing CRISPR
      structures CRISPR-S2 and CRISPR-S4, questionable CRISPR structures CRISPR-S1 and
      CRISPR-S3 in 60 Shigella strains. All primers were designed using sequences in
      CRISPR database. CRISPR Finder was used to analyze CRISPR and susceptibilities of
      Shigella strains were tested by agar diffusion method. Furthermore, we analyzed
      the relationship between drug resistance and CRISPR-S4. RESULTS: The positive
      rate of convincing CRISPR structures was 95%. The four CRISPR loci formed 12
      spectral patterns (A-L), all of which contained convincing CRISPR structures
      except type K. We found one new repeat and 12 new spacers. The multi-drug
      resistance rate was 53. 33% . We found no significant difference between CRISPR
      S4 and drug resistant. However, the repeat sequence of CRISPR-S4 in multi- or TE
      resistance strains was mainly R4.1 with AC deletions in the 3' end, and the
      spacer sequences of CRISPR-S4 in multi-drug resistance strains were mainly Sp5.1,
      Sp6.1 and Sp7. CONCLUSION: CRISPR was common in Shigella. Variations df repeat
      sequences and diversities of spacer sequences might be related to drug resistance
      in Shigella.

PMID- 26211323
TI  - [Effect of Bifidobacterium on the immunity in BALB/c mice].
AB  - OBJECTIVE: We studied the system immunofuctions of two Bifidobacterium strains
      isolated from food. METHODS: There were 10 SPF BALB/c mice in each group. The
      control group was given only sterile skim milk. The positive control group was
      given sterile skim milk containing commercial strain BB-12. The treatment group
      was given sterile skim milk containing different dosages of B. adolescentis BB-2
      or B. longum BB-3. The immune parameters including cellular immunity (delayed
      type hypersensitivity [DTH], splenic lymphocyte proliferation and natural killer
      [NK] cell activity), humoral immunity (serum hemolytic activity in immunized
      animals), and nonspecific immunity (peritoneal macrophages phagocytsis) were
      measured. RESULTS: Ingestion of B. adolescentis BB-2 or B. longum BB-3 could
      increase the DTH response. Macrophage phagocytsis was also enhanced, while
      activities of the NK cells and levels of the serum hemolysin were also
      significantly higher than that in the control group. There was a significant
      increase in splenic lymphocyte proliferation in bifidobacteria treated mice
      compared to the control. CONCLUSION: Ingestion of B. adolescentis BB-2 or B.
      longum BB-3 could enhance both innate and acquired immunity in healthy BALB/c
      mice.

PMID- 26211324
TI  - [Role of LIGHT signal pathway in Chlamydia muridarum urogenital infection in
      mice].
AB  - OBJECTIVE: To study the role of lymphotoxin-like inducible protein that competes
      with glycoprotein D for herpesvirus entry on T cells (LIGHT) in the development
      of protective immunity and pathology during Chlamydia Muridarum urogenital
      infection in mice. METHODS: C57BL/6J wild type (wt) and mice deficient in LIGHT
      (LIGHT KO) were inoculated intravaginally with 1 x 10(4) IFUs of live C.
      muridarum organisms. Half mice of each group were reinfected on day 49 after
      primary infection. We took mice vaginal swabs every 3 or 4 days to monitor live
      organism shedding. On day 80 after the primary infection, mice were sacrificed,
      the vaginal tract was isolated for pathology analysis. The spleen cells were
      collected and IL-4, IL-5, IL-17 and IFN-y were detected by ELISA in the spleen
      cells culture supernatant after restimulated by UV-MoPn EB. The titers of
      different Ab isotypes were measured in mice serum by Indirect Immunofluorescence
      Assay. RESULTS: The chlamydia shedding time of LIGHT KO mice was similar to wild
      type mice, which cleared the organisms within 28 days after primary infection,
      and acquired protective immunity against C. muridarum reinfection. All mice
      regardless of genotypes developed severe upper genital tract pathology and showed
      no significant difference between LIGHT KO and wild type mice. All mice developed
      robust anti-C. muridarum organism IgG antibody responses and the ratios of IgG2a
      versus IgG1 showed no significant difference between LIGHT KO and wild type mice.
      Splenocytes from MoPn-infected LIGHT KO and wild type mice produced high levels
      of IFN-gamma and IL-17, but IL-4 and IL-5 couldn't be detected. CONCLUSIONS:
      LIGHT signal pathway may not correlated with protection against C. muridarum
      urogenital tract infection and urogenital tract pathology induced by C.
      muridarum.

PMID- 26211325
TI  - [Indirect ELISA for simultaneous detection of antibodies against duck hepatitis A
      type 1 and 3 viruses].
AB  - OBJECTIVE: To simultaneously detect antibodies against Duck hepatitis A type 1
      (DHAV-1) and type 3 (DHAV-3) viruses, we developed an indirect enzyme-linked
      immunosobent assay (ELISA) with bacterially expressed recombinant viral protein
      as antigen in Escherichia coli. METHODS: We amplified the full-length VP3 gene of
      DHAV-1 and the full-length VP1 gene of DHAV-3 through reverse transcription
      polymerase chain reaction (RT-PCR) and then cloned them into pET-32a expression
      vector, designated as pET-1VP3-3VP1. The fusion protein DHAV-1VP3-3VP1 expressed
      correctly and was subsequently used to develop an indirect ELISA assay. RESULTS:
      DHAV-1VP3-3VP1 fusion protein expressed in BL21 (DE3) cells following induction
      by Isopropyl-beta-D-1-thiogalactopyranoside (IPTG). The expressed protein was
      very antigenic and reactive to virus-specific antibodies in western blot assay.
      The optimal working concentration for coating antigen was 1.0 microg per well and
      the working concentration of serum samples was 1:200 dilution and the cut-off
      value that distinguished the positive from negative serum samples was OD650 > OR
      = 0.38. CONCLUSION: The ELISA method based on the prokaryotic expression of VP3
      (DHAV-1) and VP1 proteins (DHAV-3) can be used effectively for the clinical
      detection antibodies against DHAV-1 and DHAV-3.

PMID- 26211326
TI  - [Establishment of genetic transformation system of Schizochytrium sp. by
      homologous recombination].
AB  - OBJECTIVE: Schizochytrium sp. is a marine fungus that can produce DHA
      efficiently. Genetic engineering has been successfully used in industrial strain
      improvement and metabolic studies. In order to use genetic engineering to
      modified Schizochytrium sp., we established an genetic transformation system of
      Schizochytrium sp. METHODS: A genetic transformation system of Schizochytrium sp.
      was established by 18S rDNA-targeted homologous recombination. The targeting
      vector contained a part of 18S rDNA from Schizochytrium sp. and the ble gene.
      This targeting vector was transformed into Schizochytrium sp. by electroporation
      and then selected by Zeocin-containing plates. The incorporation of exogenous ble
      gene into the genome of Schizochytrium was inspected by PCR amplification.
      RESULTS: Fermentation results show that the transformants had similar cell dry
      weight, lipid yield, DHA content, and composition of other fatty acids to the
      wild type strain. CONCLUSION: Our results show that the introduction of
      resistance gene did not affect the cell growth and lipid metabolism. This system
      could be used to introduce new functional genes into Schizochytrium sp.

PMID- 26211327
TI  - Incoherence in the Iraq War Narrative and the Concept of Collective Attachment.
AB  - As a major function of ideological and institutional frameworks is to provide
      security to the social group, by constructing ideologies and socio-political
      institutions, social groups also construct their objects of collective
      attachment. When social debates are conducted openly and freely, they are
      informed by secure collective attachment representations leading to effective and
      group-protecting action. When they are conducted in the context of social
      domination they are informed by insecure collective attachment representations,
      leading to ineffective and group-compromising action. The decision to invade Iraq
      in 2003 seems to have been informed by insecure collective attachment
      representations defining an incoherent social narrative and an ineffective
      protective strategy.

PMID- 26211328
TI  - Privatization and Psychoanalysis: The Impact of Neo-liberalism on Freud's Tool of
      Social Justice.
AB  - The paper outlines the historical links between psychoanalysis, social
      progressivism and the political Left. It then details the process by which those
      links were undone such that today psychoanalysis and mental health services in
      general are alienated from their radical roots. The paper posits this process of
      alienation is continued today via the neo-liberal phenomenon of privatization,
      which has profound implications for clients seeking mental health treatment
      especially those of minority status or who are economically oppressed. Today,
      access to effective mental health treatment is linked to one's economic status,
      and people of all class backgrounds seem less likely to receive mental health
      interventions that promote awareness of the oppressive political and economic
      forces they face. The paper includes two clinical vignettes illustrating the
      inequalities that are inherent to the privatized mental healthcare system. The
      paper calls for a return to the ideals and practices of the progressive
      psychoanalysis that defined the inter-war era of the last century.

PMID- 26211329
TI  - Forerunner of the Science of Psychoanalysis? An Essay on the Spanish and
      Portuguese Inquisition.
AB  - The inquisitions in Spain and Portugual were state organs, rather than church-run
      enterprises; their purpose to modernize disparate jurisdictions during the final
      stages of Reconquista (return of Moorish areas to Christian administration) to
      ensure security and loyalty. So many Jews converted (under duress or willingly
      for strategic reasons) and inter-married with middle-class and aristocratic
      families, that their sincerity and loyalty was suspected, This meant going beyond
      traditional monitoring of ritual acts and social behaviour; there was a need to
      look below the surface, to interpret ambiguity, and to break codes of duplicity.
      Inquisitors developed techniques of a form of psychoanalysis before the
      discoveries of Freud: methods of questioning to bring out repressed beliefs and
      motivations, unriddling equivocational performance and speech-acts, and
      integrating fragments of information from family members, business associates and
      neighbours collected over many years. Torture, more threatened than actual, and
      lengthy incarceration punctuated by periods of exile and re-arrest after years
      quiet, provoked desperate confessions and specious denunciations, all of which
      had to be subject to intense scrutiny and analysis. The assumption was modern: a
      person's self was no longer equivalent to their words and actions; instead, a
      deep dark and traumatized inner self to be revealed.

PMID- 26211330
TI  - A Psychological Profile of Osama bin Laden.
AB  - Understanding Osama bin Laden's personal history illuminates his motivation,
      inner conflicts, decisions and behaviors. His relationships with his mother,
      father, country and religion set the stage for his conflicted choices as an
      adolescent and then as an adult. Although only a cursory psychological profile is
      possible based on public domain information, the profile constructed here could
      be useful in setting future foreign policy. Perhaps the crucial mistake in U.S.
      foreign policy was abandoning bin Laden as an asset when Russian forces were
      expelled from Afghanistan in 1989: this act by the U.S. set the stage for the
      World Trade Center attacks on September 11, 2001.

PMID- 26211331
TI  - Nuclear War as an Anti-Sexual Group Fantasy.
AB  - What follows is a recently found unpublished paper by Lloyd deMause. It was
      originally written in 1987 or 1988 and updated in 2002. The paper covers a lot of
      ground and touches on ideas and methods that deMause has written about elsewhere
      but there is some new material as well. It touches on many of the original
      concepts that that deMause has introduced over the last 45 years.

PMID- 26211332
TI  - [The most up-to-date treatment of influenza encephalopathy].

PMID- 26211333
TI  - [A sibling case of X-linked intellectual disability].

PMID- 26211334
TI  - [To assume leadership far and wide].

PMID- 26211335
TI  - [Nerve growth factor and the physiology of pain: the relationships among
      interoception, sympathetic neurons and the emotional response indicated by the
      molecular pathophysiology of congenital insensitivity to pain with anhidrosis].
AB  - Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and
      maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA)
      is caused by loss-of-function mutations in NTRK1, which encodes a receptor
      tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of
      NGF-dependent neurons, including both NGF-dependent primary afferents and
      sympathetic postganglionic neurons, in otherwise intact systems. The NGF
      dependent primary afferents are thinly myelinated ADelta or unmyelinated C-fibers
      that are dependent on the NGF-TrkA system during development. NGF-dependent
      primary afferents are not only nociceptive neurons that transmit pain and
      temperature sensation, but also are polymodal receptors that play essential roles
      for interoception by monitoring various changes in the physiological status of
      all tissues in the body. In addition, they contribute to various inflammatory
      processes in acute, chronic and allergic inflammation. Together with sympathetic
      postganglionic neurons, they maintain the homeostasis of the body and emotional
      responses via interactions with the brain, immune and endocrine systems. Pain is
      closely related to emotions that accompany physical responses induced by systemic
      activation of the sympathetic nervous system. In contrast to a negative image of
      emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis',
      wherein emotions play critical roles in the decision-making and reasoning
      processes. According to this hypothesis, reciprocal communication between the
      brain and the body-proper are essential for emotional responses. Using the
      pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent
      neurons constitute a part of the neuronal network required for homeostasis and
      emotional responses, and indicates that this network plays important roles in
      mediating the reciprocal communication between the brain and the body-proper.

PMID- 26211336
TI  - [Introductory remarks].

PMID- 26211337
TI  - [Mini-mini history of dyslexia].

PMID- 26211338
TI  - [Clinical diagnosis of dyslexia].

PMID- 26211339
TI  - [Brain functions in developmental dyslexia].

PMID- 26211340
TI  - [Intervention in developmental dyslexia: perspective from medicine].

PMID- 26211341
TI  - [Problems surrounding dyslexia: comorbidities and secondarily emerged
      adversities].

PMID- 26211343
TI  - [Introductory remarks].

PMID- 26211342
TI  - [The prospects of the future study and medical practice].
AB  - It is thought that dyslexia is caused by brain dysfunction--specifically,
      impairment of phonological processing. Dyslexia is classified into
      neurodevelopmental disorder in DSM-5 and is described as an alternative term for
      specific learning disorder that includes reading impairment. It seems that
      dyslexia will be recognized as a separate clinical entity. As in our country,
      clinical research for diagnosis and treatment is continually progressing. Our
      original reading aloud test is recognized as an official examination for dyslexia
      diagnosis and is indicated as a mark of the fee-for-service. The time has come
      when we must regard this disorder not only as a special needs education issue but
      also as a medical subject.

PMID- 26211344
TI  - [Genetic causes of developmental disorders].

PMID- 26211345
TI  - [The influence of environmental factors].

PMID- 26211346
TI  - [Gene-environment interaction].

PMID- 26211347
TI  - [Fetal and neonatal origins for mental and developmental disorders from the stand
      point of DOHaD theory].

PMID- 26211348
TI  - [Joint researches supported by Japanese Society of Child Neurology (JSCN) The
      Committee of Joint Researches].

PMID- 26211349
TI  - [Japanese expert opinion on the management of status epilepticus in childhood].

PMID- 26211350
TI  - Worker Injuries Involving the Interaction of Cattle, Cattle Handlers, and Farm
      Structures or Equipment.
AB  - Cattle have been identified as leading sources of injuries to agricultural
      workers. The present study focused on worker injuries that involved the
      interaction of cattle, cattle handlers, and farm structures or equipment. The
      goal of the study was to identify opportunities for injury prevention. We
      examined 221 reports of injury to cattle handlers from the Consumer Product
      Safety Commission's National Electronic Injury Surveillance System (NEISS).
      Expected interactions led to many of the cattle-handling injuries reported in the
      NEISS database. In almost 30% of cases, cattle pushed workers into structures
      such as fences, gates, posts, and walls. In another 16% to 19% of injuries,
      cattle struck gates and other objects, propelling them at the victims. The
      present research makes several important contributions to the study of cattle
      handling injuries. First, the research supports an increased emphasis on the
      development of safer gate designs (e.g., gates that are remotely operated or that
      absorb energy to limit the speed at which they may be propelled by animals).
      Second, the research suggests a need for additional study of energy-absorbing
      fence and wall structures. We view these two points to be of significance because
      gates and associated structures (e.g., posts, fences, and walls) accounted for
      45% of the injuries in the dataset, based on the associated injury narrative.
      Finally, the research identifies a previously unexplored source of agricultural
      injury data, namely the NEISS database.

PMID- 26211351
TI  - The Effect of Stress, Attitudes, and Behavior on Safety during Animal Handling in
      Swedish Dairy Farming.
AB  - Working with livestock is a hazardous activity, and animals have been found to be
      the most frequent injury source on dairy farms. Understanding the risk factors
      for injury and the causal relationships related to injuries and animal handling
      is important for developing prevention strategies and effective safety
      interventions. This study examined stress and handler attitude as possible risk
      factors for animal handling injuries in dairy farming, in particular when moving
      cows. Twelve dairy farms were visited on two occasions representing different
      stress levels: when cows were being moved to milking (low stress) and to hoof
      trimming (high stress). Behavioral observations of handlers and cows were
      performed, and questionnaires were completed on attitudes (risk acceptance,
      safety locus of control, and attitudes toward cows) and stress (perceived
      stress/energy level and job strain). The injury risks were found to be higher
      when moving cows to hoof trimming compared with moving cows to milking and
      gentle, moderately forceful, and forceful interactions were more frequently used.
      When moving cows to milking, observed risk situations were related only to the
      perceived energy level of the handler. When moving cows to hoof trimming, injury
      risks were correlated to job strain and time spent in the risk zone (defined as
      the area where the handler could be hit by the cow's head or hind legs). The time
      spent in the risk zone was positively correlated with job strain, age, and
      experience. Attitudes were not found to have significant impact on safety but
      were to some extent indirectly involved. These results suggest that the main
      focus in injury reduction work should be on reducing the time the handler spends
      in close proximity to animals during aversive procedures and on minimizing cow
      fear and stress by proper handling techniques and appropriate design of handling
      facilities.

PMID- 26211352
TI  - Transforming Farm Health and Safety: The Case for Business Coaching.
AB  - In the U.S. and Australia, agriculture is consistently ranked as one of the most
      hazardous industries. The cost of injuries and deaths on Australian farms is
      significant, estimated to be between AU$0.5 billion and AU$1.2 billion per year.
      Death and injury in agriculture also place a significant financial and social
      burden on the family and friends of the injured, the community, and the health
      system. This article proposes that if farmers were to employ coaching in their
      businesses, they would benefit from advances in safety practices, resulting in
      associated improvements in overall farm productivity and a reduction in injury
      costs to the wider community. A coaching model is presented to demonstrate what
      an effective coaching process would need to include. An agenda for future
      research areas is also provided.

PMID- 26211353
TI  - Perceptions of Agricultural College Students on the Relationship between Quality
      and Safety in Agricultural Work Environments.
AB  - Agriculture is a high-hazard industry that employs a large number of young
      workers below the age of 25. Recent studies have documented a strong positive
      correlation between quality management in agriculture and occupational safety as
      perceived by agricultural workers. Younger workers have been found to be at
      higher risk for occupational injuries and fatalities in agriculture. Furthermore,
      college students in agriculture have minimal exposure to safety and quality
      management principles in their coursework and thus may not be aware that the two
      concepts are associated Little research has studied how young workers perceive
      the relationship between safety and quality and how these perceptions vary based
      on demographic characteristics. This study builds on prior research that measured
      the interactions between employee perceptions of safety and quality in an
      agricultural work environment. Data were collected using a survey instrument
      adapted from a previously validated instrument. Analysis of 1017 responses showed
      that students perceived a high impact of quality practices on the reduction of
      safety hazards and safety incidents. Students' perceptions of quality and safety
      in agricultural work environments varied by gender, with female students
      perceiving the relationship between the two at a higher level than males. No
      significant difference in perceptions was observed based on students' academic
      classification, age group, field of study, or childhood environment. This study
      demonstrates that despite limited academic training in safety and quality, pre
      professionals perceive the implementation of quality management as a very
      important factor in mitigating safety hazards and safety incidents. In addition,
      this study suggests that current academic training in these disciplines must be
      modified, since no differences in students' perceptions were observed based on
      academic classification or field of study.

PMID- 26211354
TI  - The Nurse Researcher and Scientist.

PMID- 26211355
TI  - Are Individuals With Heart Failure Being Set Up for Failure at Discharge?

PMID- 26211356
TI  - Childhood Overweight and Obesity.

PMID- 26211357
TI  - Mine Workers, Heat Related Illnesses, and the Role of the Occupational Health
      Nurse.

PMID- 26211358
TI  - Adapting Care to Culture: Aging in Agriculture.

PMID- 26211359
TI  - Electronic Cigarettes.

PMID- 26211360
TI  - Costa Rica Mission Trip.

PMID- 26211361
TI  - Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by
      Integrating Drug Sensitivity and Selectivity Profiles.
AB  - Chemical perturbation screens offer the possibility to identify actionable sets
      of cancer-specific vulnerabilities. However, most inhibitors of kinases or other
      cancer targets result in polypharmacological effects, which complicate the
      identification of target dependencies directly from the drug-response phenotypes.
      In this study, we developed a chemical systems biology approach that integrates
      comprehensive drug sensitivity and selectivity profiling to provide functional
      insights into both single and multi-target oncogenic signal addictions. When
      applied to 21 breast cancer cell lines, perturbed with 40 kinase inhibitors, the
      subtype-specific addiction patterns clustered in agreement with patient-derived
      subtypes, while showing considerable variability between the heterogeneous breast
      cancers. Experimental validation of the top predictions revealed a number of co
      dependencies between kinase targets that led to unexpected synergistic
      combinations between their inhibitors, such as dasatinib and axitinib in the
      triple-negative basal-like HCC1937 cell line. 

PMID- 26211362
TI  - Genetically Encoded Spy Peptide Fusion System to Detect Plasma Membrane-Localized
      Proteins In Vivo.
AB  - Membrane proteins are the main gatekeepers of cellular state, especially in
      neurons, serving either to maintain homeostasis or instruct response to synaptic
      input or other external signals. Visualization of membrane protein localization
      and trafficking in live cells facilitates understanding the molecular basis of
      cellular dynamics. We describe here a method for specifically labeling the plasma
      membrane-localized fraction of heterologous membrane protein expression using
      channelrhodopsins as a case study. We show that the genetically encoded, covalent
      binding SpyTag and SpyCatcher pair from the Streptococcus pyogenes fibronectin
      binding protein FbaB can selectively label membrane-localized proteins in living
      cells in culture and in vivo in Caenorhabditis elegans. The SpyTag/SpyCatcher
      covalent labeling method is highly specific, modular, and stable in living cells.
      We have used the binding pair to develop a channelrhodopsin membrane localization
      assay that is amenable to high-throughput screening for opsin discovery and
      engineering. 

PMID- 26211363
TI  - An Unaltered Orthosteric Site and a Network of Long-Range Allosteric Interactions
      for PNU-120596 in alpha7 Nicotinic Acetylcholine Receptors.
AB  - Nicotinic acetylcholine receptors (nAChRs) are vital to neuronal signaling, are
      implicated in important processes such as learning and memory, and are
      therapeutic targets for neural diseases. The alpha7 nAChR has been implicated in
      Alzheimer's disease and schizophrenia, and allosteric modulators have become one
      focus of drug development efforts. We investigate the mode of action of the
      alpha7-selective positive allosteric modulator, PNU-120596, and show that the
      higher potency of acetylcholine in the presence of PNU-120596 is not due to an
      altered agonist binding site. In addition, we propose several residues in the
      gating interface and transmembrane region that are functionally important to
      transduction of allosteric properties, and link PNU-120596, the acetylcholine
      binding region, and the receptor gate. These results suggest global protein
      stabilization from a communication network through several key residues that
      alter the gating equilibrium of the receptor while leaving the agonist binding
      properties unperturbed. 

PMID- 26211364
TI  - Thiopeptide Antibiotics Exhibit a Dual Mode of Action against Intracellular
      Pathogens by Affecting Both Host and Microbe.
AB  - Thiostrepton (TSR) is an archetypal thiopeptide antibiotic possessing a quinaldic
      acid (QA) moiety in the side ring system. According to the mechanism of TSR
      previously known to target bacterial ribosome, we recently designed and
      biosynthesized several TSR derivatives that varied in QA substitution. Utilizing
      these thiopeptide antibiotics to treat the intracellular pathogen Mycobacterium
      marinum, we herein report a novel mode of action of TSRs, which induce ER stress
      mediated autophagy to enhance host cell defense. This intracellular response,
      which is sensitive to the modification of the QA group, serves as an indirect but
      unignorable mechanism for eliminating intracellular pathogens. TSRs are thus the
      only type of antibiotics, to our knowledge, with the dual action on both the
      parasitic bacteria and the infected host cells. The newly observed mechanism of
      TSRs may inspire the future change in the treatment of intracellular pathogens,
      by taking host response into account. 

PMID- 26211365
TI  - Age-associated alterations in the somatic mutation and DNA methylation levels in
      plants.
AB  - Somatic mutations of the nuclear and mitochondrial DNA and alterations in DNA
      methylation levels in mammals are well known to play important roles in ageing
      and various diseases, yet their specific contributions await further
      investigation. For plants, it has also been proposed that unrepaired DNA damage
      and DNA polymerase errors accumulate in plant cells and lead to increased somatic
      mutation rate and alterations in transcription, which eventually contribute to
      plant ageing. A number of studies also show that DNA methylation levels vary
      depending on the age of plant tissue and chronological age of a whole plant.
      Recent studies reveal that prolonged cultivation of plant cells in vitro induces
      single nucleotide substitutions and increases global DNA methylation level in a
      time-dependent fashion. Changes in DNA methylation are known to influence DNA
      repair and can lead to altered mutation rates, and, therefore, it is interesting
      to investigate both the genetic and epigenetic integrity in relationship to
      ageing in plants. This review will summarise and discuss the current studies
      investigating somatic DNA mutation and DNA methylation levels in relation to
      plant ageing and senescence. The analysis has shown that there still remains a
      lack of clarity concerning plant biological ageing and the role of the genetic
      and epigenetic instabilities in this process. 

PMID- 26211366
TI  - Valproic acid induces NET cell growth arrest and enhances tumor suppression of
      the receptor-targeted peptide-drug conjugate via activating somatostatin receptor
      type II.
AB  - BACKGROUND: Human pancreatic carcinoids, a type of neuroendocrine tumors, are
      asymptomatic and difficult to diagnose, with the effects of traditional anti
      cancer therapies being limited. The histone deacetylase (HDAC) inhibitor valproic
      acid (VPA) was evaluated for its effects alone and in combination with receptor
      targeting peptide-drug conjugate via increasing drug internalization. MATERIALS
      AND METHODS: The in vitro and in vivo assays were used to evaluate the effects of
      VPA and somatostatin receptor-targeting camptothecin-somatostatin conjugate (CPT
      SST). RESULTS: VPA induced proliferation suppression, cell apoptosis and cell
      cycle arrest. VPA acts as a HDAC inhibitor to induce a decrease of HDAC4 and an
      increase of acetylated histone 4 (AcH4). Meanwhile, most importantly, besides
      activating Notch signaling, VPA was observed to stimulate the expression of
      somatostatin receptor type 2 (SSTR2) that has been applied for receptor-targeting
      therapies. This characteristic was used for a combination therapy of VPA and CPT
      SST. The combination displayed much more potent anti-tumor effects on carcinoid
      tumor growth by increasing SSTR2 density and drug internalization in target tumor
      cells. CONCLUSION: The combination of VPA and a SSTR2-targeting agent provides us
      a promising approach in treatment of carcinoid tumors.

PMID- 26211367
TI  - Targeting non-receptor tyrosine kinases using small molecule inhibitors: an
      overview of recent advances.
AB  - Protein tyrosine kinases are enzymes that catalyze the transfer of phosphate
      groups from ATP to tyrosine residues on other proteins as substrate.
      Phosphorylation at tyrosine residues regulates several functions, including
      enzyme activity, cellular localization, signal transduction and interactions
      between proteins. Non-receptor tyrosine kinases (nRTKs) are one of the main
      players in intracellular signaling pathways. Dysregulation of nRTKs leads to
      their constitutive activation, which might contribute to initiation or
      progression of cancer. Therefore, targeting dysregulated nRTKs may prevent the
      process of tumorigenesis. Targeted-based cancer therapy (TBCT) methods and agents
      or personalized medicine have emerged as the main tools for cancer treatment.
      Currently, several TBCT agents, including monoclonal antibodies (mAbs) and small
      molecules inhibitors of tyrosine kinases (TKIs) have been developed. TKIs of
      cytoplasmic kinases inhibit intracellular signaling pathways and interfere with
      tumor cell functions. In this article, the recent progresses in development of
      TKIs of nRTKs approved by the US Food and Drug Administration (FDA) and current
      promising TKIs in pre-clinical and clinical settings have been reviewed. 

PMID- 26211368
TI  - Proteome-Wide Profiling of Targets of Cysteine reactive Small Molecules by Using
      Ethynyl Benziodoxolone Reagents.
AB  - In this study, we present a highly efficient method for proteomic profiling of
      cysteine residues in complex proteomes and in living cells. Our method is based
      on alkynylation of cysteines in complex proteomes using a "clickable" alkynyl
      benziodoxolone bearing an azide group. This reaction proceeds fast, under mild
      physiological conditions, and with a very high degree of chemoselectivity. The
      formed azide-capped alkynyl-cysteine adducts are readily detectable by LC-MS/MS,
      and can be further functionalized with TAMRA or biotin alkyne via CuAAC. We
      demonstrate the utility of alkynyl benziodoxolones for chemical proteomics
      applications by identifying the proteomic targets of curcumin, a diarylheptanoid
      natural product that was and still is part of multiple human clinical trials as
      anticancer agent. Our results demonstrate that curcumin covalently modifies
      several key players of cellular signaling and metabolism, most notably the enzyme
      casein kinase I gamma. We anticipate that this new method for cysteine profiling
      will find broad application in chemical proteomics and drug discovery. 

PMID- 26211370
TI  - Editorial Comment from Dr Cantiello and Dr Damiano to Emerging links between non
      neurogenic lower urinary tract symptoms secondary to benign prostatic
      obstruction, metabolic syndrome and its components: A systematic review.

PMID- 26211369
TI  - Genetically modified proteins: functional improvement and chimeragenesis.
AB  - This review focuses on the emerging role of site-specific mutagenesis and
      chimeragenesis for the functional improvement of proteins in areas where
      traditional protein engineering methods have been extensively used and
      practically exhausted. The novel path for the creation of the novel proteins has
      been created on the farther development of the new structure and sequence
      optimization algorithms for generating and designing the accurate structure
      models in result of x-ray crystallography studies of a lot of proteins and their
      mutant forms. Artificial genetic modifications aim to expand nature's repertoire
      of biomolecules. One of the most exciting potential results of mutagenesis or
      chimeragenesis finding could be design of effective diagnostics, bio-therapeutics
      and biocatalysts. A sampling of recent examples is listed below for the in vivo
      and in vitro genetically improvement of various binding protein and enzyme
      functions, with references for more in-depth study provided for the reader's
      benefit. 

PMID- 26211371
TI  - Does prolactin mediate parental and life-history decisions in response to
      environmental conditions in birds? A review.
AB  - This article is part of a Special Issue "Parental Care". In vertebrates,
      adjustments of physiology and behavior to environmental changes are often
      mediated by central physiological mechanisms, and more specifically by hormonal
      mechanisms. As a consequence, these mechanisms are thought to orchestrate life
      history decisions in wild vertebrates. For instance, investigating the hormonal
      regulation of parental behavior is relevant to evaluate how parents modulate
      their effort according to specific environmental conditions. Surprisingly and
      despite being classically known as the 'parental hormone', prolactin has been
      overlooked in birds relative to this context. Our aim is to review evidence that
      changes in prolactin levels can mediate, at least to some extent, the response of
      breeding birds to environmental conditions. To do so, we first examine current
      evidence and limits for the role of prolactin in mediating parental behavior in
      birds. Second, we emphasize the influence of environmental conditions and
      stressors on circulating prolactin levels. In addition, we review to what extent
      prolactin levels are a reliable predictor of breeding success in wild birds. By
      linking environmental conditions, prolactin regulation, parental behavior, and
      breeding success, we highlight the potential role of this hormone in mediating
      parental decisions in birds. Finally, we also review the potential role of
      prolactin in mediating other life history decisions such as clutch size, re
      nesting, and the timing of molt. By evaluating the influence of stressors on
      circulating prolactin levels during these other life-history decisions, we also
      raise new hypotheses regarding the potential of the prolactin stress response to
      regulate the orchestration of the annual cycle when environmental changes occur.
      To sum up, we show in this review that prolactin regulation has a strong
      potential to allow ecological physiologists to better understand how individuals
      adjust their life-history decisions (clutch size, parental behavior, re-nesting,
      and onset of molt) according to the environmental conditions they encounter and
      we encourage further research on that topic. 

PMID- 26211375
TI  - Are Clinical Characteristics of Patients with Sepsis Codes Changing over Time?

PMID- 26211376
TI  - Multicenter clinical trial of the conformable stent graft for the treatment of
      acute, complicated type B dissection.
AB  - OBJECTIVE: The treatment of acute, complicated type B aortic dissection has
      evolved in the past several decades. Thoracic endovascular aortic repair when
      anatomy is suitable, has been regarded as the preferable treatment to seal the
      primary entry tear, redirect and re-establish adequate true lumen flow, and
      thereby promote aortic remodeling. This study was designed to determine the
      safety and efficacy of a conformable thoracic endoprosthesis device for patients
      with acute, complicated type B aortic dissection, defined as malperfusion or
      rupture or both. METHODS: Between January 2010 and January 2012, 50 patients with
      complicated type B aortic dissection from 26 sites in the United States were
      included in this prospective, multicenter, nonrandomized single-arm study. The
      primary safety end point was all-cause mortality through 30 days after treatment,
      and the primary efficacy end point was exclusion of the primary entry tear (Core
      Laboratory adjudicated) at 1-month follow-up. Secondary end points included false
      lumen thrombosis, dissection-based reintervention rate, and aortic rupture.
      RESULTS: All device implants were successfully completed. Six patients (12%)
      required additional device implantations <=1 year from the index procedure. There
      was no conversion to open repair at 1 year. Exclusion of the primary entry tear
      at 30 days occurred in 97.5% of patients. All-cause mortality through 30 days was
      8%. Survival was 88% at 1 year and 85% at 2 years. At 1 year after treatment,
      35.1% of patients had experienced a decrease of >=5 mm in overall diameter in the
      treated segment of the aorta. From pretreatment to the 36-month follow-up, the
      average minimum true lumen area increased by 206.3 mm(2), and the average maximum
      false lumen area decreased by 313.4 mm(2). The 30-day stroke rate was 18%; none
      were fatal, and one permanent deficit occurred. Four patients (8%) experienced
      spinal cord ischemia of any severity but without any permanent or significant
      deficits. New aortic dissection (3 retrograde, 2 de novo) occurred in five
      patients (10%). The secondary intervention rate was 18%. CONCLUSIONS: Treatment
      with the conformable thoracic endovascular aortic repair device produced
      favorable perioperative and intermediate level clinical and anatomic outcomes. In
      particular, an operative mortality of 8% in this cohort is comparable to that
      noted in a Society for Vascular Surgery objective performance criteria
      publication. Late survival in our cohort compares favorably with historical data
      referable to complicated type B dissection.

PMID- 26211377
TI  - Results of aberrant right subclavian artery aneurysm repair.
AB  - OBJECTIVE: The objective of this multicenter registry was to review current
      treatments and late results of repair of aneurysm of aberrant right subclavian
      artery (AARSA). METHODS: All consecutive AARSA repairs from 2006 to 2013 in seven
      centers were reviewed. End points were 30-day and late mortality, reintervention
      rate, and AARSA-related death. RESULTS: Twenty-one AARSA repairs were included
      (57% men; mean age, 67 years); 3 ruptures (14%) required emergent treatment; 12
      (57%) were symptomatic for dysphagia (33%), dysphonia (24%), or pain (19%). Eight
      cases (38%) presented with thoracic aortic aneurysm, two with intramural
      hematoma, and one with acute type B aortic dissection. Mean AARSA diameter was
      4.2 cm; a single bicarotid common trunk was present in 38% of cases. The majority
      of patients underwent hybrid intervention (n = 15; 71%) consisting of single (n =
      2) or bilateral (n = 12) subclavian to carotid transposition or bypass or
      ascending aorta to subclavian bypass (n = 1) plus thoracic endovascular aortic
      repair (TEVAR); 19% of cases underwent open repair and 9% simple TEVAR with AARSA
      overstenting. Perioperative death occurred in two patients (9%): in one case
      after TEVAR in ruptured AARSA, requiring secondary sternotomy and aortic banding;
      and in an elective case due to multiorgan failure after a hybrid procedure.
      Median follow-up was 30 (interquartile range, 15-46) months. The Kaplan-Meier
      estimate of survival at 36 months was 90% (standard error, 0.64). Late AARSA
      related death in one case was due to AARSA-esophageal fistula presenting with
      continuing backflow from distal AARSA and previous TEVAR. At computed tomography
      controls, one type I endoleak and one type II endoleak were detected; the latter
      required reintervention by aneurysm wrapping and ligature of collaterals. AARSA
      related death was more frequent after TEVAR, a procedure reserved for ruptures,
      compared with elective open or hybrid repair. CONCLUSIONS: Hybrid repair is the
      preferred therapeutic option for patients presenting with AARSA. Midterm results
      show high rates of clinical success with low risk of reintervention. Simple
      endografting presents high risk of related death; these findings underline the
      importance of achieving complete sealing to avoid treatment failures.

PMID- 26211379
TI  - Discussion.

PMID- 26211378
TI  - Comparison of domain-specific cognitive function after carotid endarterectomy and
      stenting.
AB  - BACKGROUND: Observational data indicate that carotid artery stenting (CAS) is
      associated with higher incidence of subclinical cerebral microemboli than carotid
      endarterectomy (CEA). We hypothesized that CEA would be associated with superior
      performance on detailed domain-specific cognitive testing compared with CAS.
      METHODS: Patients with >80% asymptomatic carotid artery stenosis were randomized
      to CEA or CAS with side of stenosis balanced across condition. A robust battery
      of tests was used to assess the cognitive domains of attention, memory, mood,
      visual-spatial skills, motor ability, processing speed, and executive functioning
      <=10 days preoperatively and postoperatively at 6 weeks and 6 months. Tests were
      administered using standardized conditions and were scored by individuals blinded
      to treatment allocation. RESULTS: Baseline cognitive performance was similar
      between CAS (n = 29) and CEA (n = 31) groups (P > .05). Relative to baseline,
      verbal and visual memory and attention functions substantially improved in the
      CAS and CEA groups at 6 months (multiple cognitive tests achieved statistical
      significance). Compared with CEA, cognitive processing speed (Stroop Color test:
      9.0 vs 7.3, P = .04; and Stroop Word test: 9.0 vs 7.4, P = .05) was superior in
      the CAS group at 6 weeks. Executive functioning (phonemic verbal fluency: 10.6 vs
      8.4, P = .043) and motor function (Grooved Pegboard of nondominant extremity:
      45.7 vs 38.9, P = .022) were also superior in the CAS group at 6 months. Tests of
      attention, memory, and visual-spatial skills were similar between CAS and CEA
      patients at 6 weeks and 6 months. CONCLUSIONS: Carotid revascularization improves
      memory and attention within the first 6 postoperative months. Compared with CEA,
      CAS produces improvements in cognitive processing speed, executive functioning,
      and motor function.

PMID- 26211380
TI  - Delayed pseudoaneurysm after below-knee amputation.

PMID- 26211381
TI  - Adventitial cystic disease of the popliteal artery.

PMID- 26211382
TI  - Health-related quality-of-life outcomes after open versus endovascular abdominal
      aortic aneurysm repair.
AB  - OBJECTIVE: Endovascular repair (EVAR) of abdominal aortic aneurysms is a safe
      alternative to open aneurysm repair (OAR) in selected patients. The aim of this
      study was to compare the health-related quality-of-life (HR-QoL) outcomes of
      patients following EVAR and OAR. METHODS: A literature search of PubMed, EMBASE,
      and the Cochrane Library identified five randomized trials that reported on HR
      QoL in EVAR and OAR for elective management of infrarenal abdominal aortic
      aneurysms. No consistent HR-QOL instrument was used among the studies. A meta
      analysis was performed on the 36-Item Short Form (SF-36) and the EuroQol-5D (EQ
      5D) HR-QoL results. RESULTS: SF-36 general health scores were higher for EVAR at
      3, 6, and 12 months postoperatively. SF-36 physical functioning scores were
      higher for EVAR at 6 months but this advantage was lost at 12 months. In
      addition, SF-36 social functioning scores were higher for EVAR at 12 months. SF
      36 component summary scores were not significantly different. EVAR was associated
      with a better EQ-5D score at 3, 6, and 12 months, but not at 24 months of follow
      up. CONCLUSIONS: EVAR was associated with better HR-QoL in some domains up to 12
      months postoperatively. There is insufficient data to demonstrate a HR-QoL
      advantage beyond 12 months. More studies are required to examine any long-term HR
      QoL advantages for either intervention.

PMID- 26211383
TI  - Update in preoperative risk assessment in vascular surgery patients.
AB  - Multiple clinical factors and now serum biomarkers may aid with risk
      stratification in vascular surgical patients. Herein, we review and update the
      clinical risk models, biomarker data, and currently used noninvasive cardiac
      stress tests. We also review the most recent American Heart Association guideline
      changes, and suggest a pathway for risk stratification.

PMID- 26211384
TI  - What is meant by high-risk informed consent?
AB  - Dr S.C. Alpel is a renowned complex aneurysm surgeon, accepting difficult cases
      from around the world. He has an English-speaking patient from the Middle East
      who has a very large life-threatening aneurysm. The patient is in the mid-70s, is
      frail with multiple comorbidities, and needs extensive open surgery. How does the
      standard Informed consent process need to be altered? A. An interpreter should be
      present B. The surrogate should be present and participate C. All possible
      serious complications, including prolonged life support, should be detailed D.
      The patient must be questioned about his end-of-life wishes E. All of the above
      should be included

PMID- 26211385
TI  - Regarding "Severe bilateral renal artery stenosis after transluminal
      radiofrequency ablation of renal sympathetic nerve plexus".

PMID- 26211386
TI  - Reply: To PMID 24468285.

PMID- 26211387
TI  - Regarding "Novel temporary endovascular shunt technique to assist in situ
      fenestration for endovascular reconstruction of the distal aortic arch".

PMID- 26211388
TI  - Prevalence and patterns of antimicrobial resistance among Escherichia coli
      isolated from Zambian dairy cattle across different production systems.
AB  - This study focused on the use of antibiotics on small, medium and commercial
      sized dairy farms in the central region of Zambia and its relationship to
      antibiotic resistance in Escherichia coli. A stratified random sample of 104
      farms was studied, representing approximately 20% of all dairy farms in the
      region. On each farm, faecal samples were collected from a random sample of
      animals and a standardised questionnaire on the usage of antibiotics was
      completed. An E. coli isolate was obtained from 98.67% (371/376) of the sampled
      animals and tested for resistance to six classes of antibiotics. The estimated
      prevalence of resistance across the different farming systems was: tetracycline
      (10.61; 95%CI: 7.40-13.82), ampicillin (6.02; 95%CI: 3.31-8.73),
      sulfamethoxazole/ trimethoprim (4.49; 95%CI: 2.42-6.56), cefpodoxime (1.91;
      95%CI: 0.46-3.36), gentamicin (0.89; 95%CI: 0.06-1.84) and ciprofloxacin (0%).
      Univariate analyses indicated certain diseases, exotic breeds, location, farm
      size and certain management practices as risk factors for detection of
      resistance, whereas multivariate analyses showed an association with lumpy skin
      disease and a protective effect for older animals (>25 months). This study has
      provided novel insights into the drivers of antibiotic use and their association
      with antibiotic resistance in an under-studied region of Southern Africa. 

PMID- 26211389
TI  - A unique blue spot.
AB  - We report the unusual case of a 3-year-old child with a Mongolian blue spot
      present both around the auricle externally and on the tympanic membrane itself. 

PMID- 26211390
TI  - Community Discharge of Nursing Home Residents: The Role of Facility
      Characteristics.
AB  - OBJECTIVE: Using a socio-ecological model, this study examines the influence of
      facility characteristics on the transition of nursing home residents to the
      community after a short stay (within 90 days of admission) or long stay (365 days
      of admission) across states with different long-term services and supports
      systems. DATA SOURCE: Data were drawn from the Minimum Data Set, the federal
      Online Survey, Certification, and Reporting (OSCAR) database, the Area Health
      Resource File, and the LTCFocUs.org database for all free-standing, certified
      nursing homes in California (n = 1,127) and Florida (n = 657) from July 2007 to
      June 2008. STUDY DESIGN: Hierarchical generalized linear models were used to
      examine the impact of facility characteristics on the probability of
      transitioning to the community. PRINCIPAL FINDINGS: Facility characteristics,
      including size, occupancy, ownership, average length of stay, proportion of
      Medicare and Medicaid residents, and the proportion of residents admitted from
      acute care facilities are associated with discharge but differed by state and
      whether the discharge occurred after a short or long stay. CONCLUSION: Short- and
      long-stay nursing home discharge to the community is affected by resident,
      facility, and sometimes market characteristics, with Medicaid consistently
      influencing discharge in both states.

PMID- 26211391
TI  - Correlation of the osteoarthritis susceptibility variants that map to chromosome
      20q13 with an expression quantitative trait locus operating on NCOA3 and with
      functional variation at the polymorphism rs116855380.
AB  - OBJECTIVE: To functionally characterize the osteoarthritis (OA) susceptibility
      variants that map to a region of high linkage disequilibrium (LD) on chromosome
      20q13 marked by the single-nucleotide polymorphism (SNP) rs6094710 and
      encompassing NCOA3 and SULF2. METHODS: Nucleic acids were extracted from the
      cartilage of OA patients. Overall and allelic expression of NCOA3 and SULF2 were
      measured by quantitative reverse transcription-polymerase chain reaction and
      pyrosequencing, respectively. The functional effect of SNPs within the 20q13
      locus was assessed in vitro using luciferase reporter constructs and
      electrophoretic mobility shift assays (EMSAs). The in vivo effect of nuclear
      receptor coactivator 3 (NCOA3) protein depletion on primary human OA articular
      cartilage chondrocytes was assessed using RNA interference. RESULTS: Expression
      of NCOA3 correlated with the genotype at rs6094710 (P = 0.006), and the gene
      demonstrated allelic expression imbalance (AEI) in individuals heterozygous for
      the SNP (mean AEI 1.21; P < 0.0001). In both instances, expression of the OA
      associated allele was reduced. In addition, there was reduced enhancer activity
      of the OA-associated allele of rs116855380, a SNP in perfect LD with rs6094710 in
      luciferase assays (P < 0.001). EMSAs demonstrated a protein complex binding with
      reduced affinity to this allele. Depletion of NCOA3 led to significant changes
      (all P < 0.05) in the expression of genes involved in cartilage homeostasis.
      CONCLUSION: NCOA3 is subject to a cis-acting expression quantitative trait locus
      in articular cartilage, which correlates with the OA association signal and with
      the OA-associated allele of the functional SNP rs116855380, a SNP that is located
      only 10.3 kb upstream of NCOA3. These findings elucidate the effect of the
      association of the 20q13 region on OA cartilage and provide compelling evidence
      of a potentially causal candidate SNP.

PMID- 26211393
TI  - The Food Preferences of the Blow Fly Lucilia cuprina Offered Human Blood, Semen
      and Saliva, and Various Nonhuman Foods Sources.
AB  - As human DNA profiles can be obtained from blow fly artifacts, this study aimed
      to establish the feeding preferences of Lucilia cuprina (Wiedemann) blow flies
      when offered human biological fluids and nonhuman food sources. One-day-old and 3
      day-old blow flies of both sexes were simultaneously offered human blood, semen
      and saliva, pet food, canned tuna and honey, and the number and length of visits
      documented over 6 h. One-day-old flies visited pet food and honey most often, but
      stayed longest on honey and semen. Three-day-old flies visited semen and pet food
      most often, and stayed longest on these food sources. Blood and saliva were the
      least preferred options for all flies. Overall, flies preferred dry blood and
      semen to the wet forms. These findings demonstrate that even when other food
      sources are available, flies at a crime scene may feed on human biological fluids
      if present, potentially transferring human DNA.

PMID- 26211392
TI  - Injecting Drug Use Among Mexican Female Sex Workers on the US-Mexico Border.
AB  - Both injecting drug users (IDU) and sex workers are at great risk of contracting
      and transmitting HIV. Therefore, IDU sex workers could be at especially high
      risk. The recent increase of HIV infection in Mexico has caused increased
      attention to sex work. We identify the correlates of injecting drug use including
      socio-demographic, work history, and sexual and non-injecting drug use risk
      behaviors among Mexican female sex workers. There is a high risk profile for IDUs
      compared to never injectors including a high prevalence of lifetime STI infection
      (54.2%). Revealed is an environment composed of high-risk networks that may have
      serious binational public health implications. 

PMID- 26211394
TI  - Clinical outcomes of tracheoesophageal diversion and laryngotracheal separation
      for aspiration in patients with severe motor and intellectual disability.
AB  - CONCLUSIONS: Tracheoesophageal diversion (TED) and laryngotracheal separation
      (LTS) can prevent aspiration pneumonia and improve the morbidity of patients with
      severe motor and intellectual disability (SMID). By improving hospitalization
      rates and care needs, the quality-of-life can be improved for the patients and
      their parents. OBJECTIVES: This study evaluated the clinical outcomes of TED and
      LTS in patients with intractable aspiration and SMID. METHODS: This study
      retrospectively reviewed patients with SMID and intractable aspiration pneumonia
      who underwent TED or LTS at the institution between January 2008 and January
      2015. It assessed the frequency of sputum suctioning, the number of pre-operative
      and post-operative hospitalizations, the operative time, and complications.
      RESULTS: Forty patients were identified during the study period. After surgery,
      there were significant reductions in the frequency of secretion suctioning (from
      165.0 times/day to 33.0 times/day) and the number of hospitalizations because of
      aspiration pneumonia (from 5.4 times/year to 0.2 times/year). A tracheocutaneous
      fistula occurred in one (2.5%) patient, and two (5.4%) patients developed
      tracheoinnominate artery fistulas. In the latter group, the innominate arteries
      were successfully ligated and endovascular embolization was performed.

PMID- 26211395
TI  - Children's perception of caries and gingivitis as determinants of oral health
      behaviours: a cross-sectional study.
AB  - AIM: To evaluate the relationship between children's perception of caries and
      gingivitis and their oral health behaviours. DESIGN: Participants in this cross
      sectional study were children aged 11-14 years. A questionnaire for measuring
      children's perceptions and behaviours was developed, validated and applied.
      Perceptions were analysed as predictors for behaviours using multiple logistic
      regression analysis. RESULTS: A total of 434 children (57% males) participated in
      the study. Half of them perceived caries as a disease and believed in visiting
      the dentist regularly regardless of dental need. More than 60% were unaware that
      gum bleeding is a sign of disease and only 60.7% believed that it requires a
      management. Being aware that gum bleeding is a sign of disease and that it
      requires treatment increased the odds of brushing 2.83 (OR = 2.83, 95% CI:1.33
      6.12) and 2.1 (OR = 2.1, 95% CI:1.05-5.55) times, respectively. Children aware of
      importance of dental visits even without dental decay were 2.9 times more likely
      to visit the dentist regularly (OR = 2.86, 95% CI:1.25-5.75) and were 77% more
      likely to never miss a dental appointment (OR = 1.77, 95% CI:1.03-3.37).
      CONCLUSION: Being aware that bleeding gum requires treatment was a determinant of
      toothbrushing habit. Improved perceived need for dental check-up regardless of
      dental problem may promote children's preventive dental attendance.

PMID- 26211396
TI  - Adalimumab for the treatment of pediatric Crohn's disease.
AB  - Inflammatory bowel diseases are characterized by a chronic relapsing course, high
      morbidity and impaired quality of life. Their incidence is rising, and about 25%
      of cases are diagnosed in pediatric age. Anti-TNF-alpha antibodies, such as
      infliximab and adalimumab (ADA), are usually administered in patients refractory
      to conventional therapies. However, increasing evidence suggests that they can be
      introduced earlier in the course of the disease, especially in patients with
      aggressive and extensive disease since diagnosis. ADA is a fully human anti-TNF
      alpha antibody recently approved for pediatric Crohn's disease not only in
      patients unresponsive to infliximab, but also as a first-line anti-TNF-alpha
      therapy. In this review, we aim to summarize the current knowledge on the use of
      ADA in pediatric Crohn's disease and to discuss open issues regarding safety as
      well as future perspectives. 

PMID- 26211397
TI  - Optimization of LTQ-Orbitrap Mass Spectrometer Parameters for the Identification
      of ADP-Ribosylation Sites.
AB  - ADP-ribosylation of proteins alters their function or provides a scaffold for the
      recruitment of other proteins, thereby regulating several important cellular
      processes. Mono- or poly-ADP-ribosylation is catalyzed by different ADP
      ribosyltransferases (ARTs) that have different subcellular localizations and
      modify different amino acid acceptor sites. However, our knowledge of ADP
      ribosylated proteins and their acceptor amino acids is still limited due to the
      lack of suitable mass spectrometry (MS) tools. Here, we describe an MS approach
      for the detection of ADP-ribosylated peptides and identification of the ADP
      ribose acceptor sites, combining higher-energy collisional dissociation (HCD) and
      electron-transfer dissociation (ETD) on an LTQ-Orbitrap mass spectrometer. The
      presence of diagnostic ions of ADP-ribose in the HCD spectra allowed us to detect
      putative ADP-ribosylated peptides to target in a second LC-MS/MS analysis. The
      combination of HCD with ETD fragmentation gave a more comprehensive coverage of
      ADP-ribosylation sites than that with HCD alone. We successfully identified
      different ADP-ribose acceptor sites on several in vitro modified proteins. The
      combination of optimized HCD and ETD methods may be applied to complex samples,
      allowing comprehensive identification of ADP-ribosylation acceptor sites. 

PMID- 26211398
TI  - Intercorrelations and developmental pathways of mothers' and fathers' loneliness
      during pregnancy, infancy and toddlerhood--STEPS study.
AB  - Our aim was to study the inter-correlations and developmental pathways of
      mothers' and fathers' social and emotional loneliness during pregnancy (20th
      pregnancy week), infancy (child aged 8 months), and early childhood (child aged
      18 months). Moreover, we aimed to study whether mothers and fathers who have
      different developmental profiles (identified by latent growth curve mixture
      models) differ in their experiences of marital dissatisfaction (RDAS), social
      phobia (SPIN) and depression (BDI) during pregnancy. Both mothers' social and
      emotional loneliness and fathers' social and emotional loneliness were highly
      stable, and within individuals these loneliness factors were strongly correlated.
      However, the correlations between mothers' loneliness experiences and fathers'
      loneliness experiences were weaker than expected. Separate latent growth curve
      groups were identified, which differed in feelings of marital dissatisfaction,
      social phobia, and depression. These groupings revealed that the higher the
      loneliness was, the more the parents experience these other psychosocial
      problems. 

PMID- 26211399
TI  - Graphene/Single-Walled Carbon Nanotube Composites Generated by Covalent Cross
      Linking.
AB  - Composites of graphene and single-walled carbon nanotubes (SWNT) have been
      generated by covalent cross-linking through two different coupling strategies,
      namely Sonogashira and EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide)
      coupling reactions. The obtained assemblies have been characterized by various
      microscopic and spectroscopic techniques. The assemblies obtained by Sonogashira
      coupling exhibit high surface area, the value increasing with the graphene
      content. The highest surface area obtained is 1260 m(2) g(-1) in the composition
      with highest graphene content (graphene:SWNT 1:4). These composites show a
      uniform slit-shaped porous network with pores of approximately 1-2 nm. CO2 uptake
      of this assemblies is in the range 11-15 wt % at 273 K (1 atm) and 9-11 wt % at
      298 K (1 atm), whereas the H2 uptake is in the 1-1.3 wt % range at 77 K (1 atm).
      The composites generated by Sonogashira coupling show superhydrophobicity with
      high contact angles in the range from 159-163 degrees . The EDC-coupled
      composites show less surface area than the composites from Sonogashira coupling.

PMID- 26211403
TI  - Bronchial deformation associated with lobectomy.

PMID- 26211402
TI  - A fetal sheep model for studying compensatory mechanisms in the healthy
      contralateral kidney after unilateral ureteral obstruction.
AB  - INTRODUCTION: Fetal unilateral ureteral obstruction (UUO) triggers complex
      pathophysiology involving not only the affected organ but also the contralateral
      kidney, which undergoes evident compensatory changes. OBJECTIVE: We hypothesized
      that it would be possible to characterize a transcriptomic fingerprint and
      selected molecular mechanisms for compensatory growth of contralateral kidneys in
      UUO, specifically focusing on mediators, carriers, membrane transport, and organ
      crosstalk in an ovine fetal UUO model. STUDY DESIGN: A fetal ovine model of
      complete UUO was created on the 60th day of gestation. For transcriptomics
      profiling, total RNA was extracted from vital renal biopsies of contralateral
      (non-obstructed) kidneys harvested on the 80th day of gestation, and kidneys of
      untreated fetuses served as controls. Statistical analysis provided the set of
      differentially regulated genes further forwarded to bioinformatics analysis for
      identification of eventual compensatory molecular mechanisms. Histological
      analysis was performed with hematoxylin and eosin and periodic acid-Schiff
      stains. RESULTS: Contralateral kidneys showed compensatory hypertrophic renal
      growth, represented on the molecular side by 324 protein coding genes
      differentially regulated compared with the control kidney samples. Bioinformatics
      analysis identified an interactome (Figure) consisting of 102 genes with 108
      interactions mainly involving transporters (protein transport and protein
      localization as well as in protein degradation), signaling molecules,
      DNA/nucleotide/RNA processing, and components of catabolism and cell cycle
      regulation. Within the interactome, nine receptors were identified as
      differentially regulated on the contralateral kidney, involving potential
      renoprotective ligands of the prostaglandin and the bradykinin receptor, arginine
      vasopressin receptor 1B, and integrin beta 4. Interestingly, a broad range of
      molecules found differentially expressed, has been previously described in stress
      response, renoprotection and repair (e.g., MAPK3, MCP1, DICER1, and others).
      DISCUSSION: The compensatory renal growth interactome provides a network of
      transcripts significantly altered in the contralateral kidney, potentially
      allowing novel insights into mechanisms, interactions, and signaling pathways
      associated with compensatory growth, and renal protection and repair.
      Interestingly, the finding of an embedded gene signature reflecting signaling and
      communication suggests a key role of these processes in CRG either by crosstalk,
      soluble substances, carriers, or membrane signaling. CONCLUSIONS: Using a
      transcriptomics approach, it was possible to identify a gene expression
      fingerprint of contralateral renal growth in a fetal UUO model. Further studies
      are warranted to validate those processes and to allow incorporation of this
      knowledge in new fetal diagnostic or even therapeutic strategies.

PMID- 26211405
TI  - Cardiovascular surgery in Jehovah's Witness patients: The role of preoperative
      optimization.
AB  - OBJECTIVE: We aimed to identify factors associated with adverse outcomes in
      Jehovah's Witness patients undergoing complex cardiovascular surgery and to
      validate our preoperative optimization protocol. METHODS: We retrospectively
      reviewed 144 Jehovah's Witnesses who underwent cardiovascular surgery between
      1999 and 2014. We excluded 7 salvage cases. The operative procedures included 56
      coronary artery bypass graft surgeries, 43 valve procedures, 13 ventricular
      assist device implantations, 11 heart transplantations, 9 aortic surgeries, and 5
      congenital defect repairs. Our preoperative optimization protocol for Jehovah's
      Witnesses includes discontinuing antiplatelets and adding iron/vitamin or
      erythropoietin to achieve a target hemoglobin greater than 12 g/dL. We evaluated
      the risk factors for postoperative mortality and composite outcomes (mortality,
      myocardial infarction, stroke, acute kidney injury, heart failure, sternal wound
      infection), and compared the outcomes of optimized patients with a preoperative
      hemoglobin level greater than 12 g/dL (n = 93) versus unoptimized patients with a
      preoperative hemoglobin level less than 12 g/dL (n = 44). RESULTS: Preoperative
      and intraoperative demographics in the optimized and unoptimized groups were
      similar except for preoperative hemoglobin levels, renal dysfunction (optimized =
      25/93 [26.9%], unoptimized = 26/44 [59.1%], P < .001), and emergency/urgent cases
      (optimized = 20/93 [21.5%], unoptimized = 17/44 [38.6%], P = .035). The mean
      preoperative, intraoperative nadir, and discharge hemoglobin levels of the entire
      cohort were 12.7 +/- 1.7 g/dL, 9.5 +/- 2.6 g/dL, and 9.7 +/- 1.8 g/dL,
      respectively. Hospital mortality was 9 of 137 patients (6.6%) (optimized = 2/93
      [2.2%], unoptimized = 7/44 [15.9%], P = .002), and composite outcomes were
      observed in 44 of 137 patients (32.1%) (optimized = 21/93 [22.6%], unoptimized =
      22/44 [50.0%], P = .001). The Youden index identified a cutoff value of the
      preoperative hemoglobin of 11.7 g/dL for mortality (area under curve, 0.719;
      sensitivity, 77.8%; specificity, 76.0%). Multivariate analysis identified a
      suboptimal preoperative hemoglobin (<12 g/dL) as the only important independent
      factor associated with mortality (odds ratio, 5.64; 95% confidence interval, 1.14
      42.18) and composite outcomes (odds ratio, 2.49; 95% confidence interval, 1.06
      5.88). CONCLUSIONS: Complex cardiovascular surgery in Jehovah's Witnesses was
      associated with acceptable surgical outcomes, especially if they electively
      completed optimization. Our Jehovah's Witnesses' optimization protocol targeting
      a hemoglobin level greater than 12 g/dL seemed to be effective in reducing
      adverse events at The University of Chicago Medicine.

PMID- 26211406
TI  - Are all forms of total arterial revascularization equal? A comparison of single
      versus bilateral internal thoracic artery grafting strategies.
AB  - OBJECTIVE: Total arterial revascularization (TAR) with internal thoracic arteries
      (ITAs) and radial arteries (RA) is associated with greater long-term survival
      compared with the use of a single internal thoracic artery supplemented by veins.
      The optimal conduit choice and configuration in achieving TAR remains
      controversial, with uncertainty regarding the individual prognostic impact of
      ITAs and RAs. As such, among patients solely undergoing TAR, we compared long
      term survival between patients receiving single thoracic arteries and those
      receiving bilateral ITAs. METHODS: From 1995 to 2010, 2821 patients with 3-vessel
      coronary artery disease at 8 centers underwent primary isolated coronary artery
      bypass with TAR using ITAs and RAs. Bilateral ITAs were used in 912 patients. In
      380 cases, bilateral in situ ITAs were grafted to the left coronary system. RAs
      were used in 848 patients (93%) receiving bilateral ITAs and 1906 patients
      (99.8%) receiving single ITAs. Survival data were obtained using the National
      Death Index. Separate 1:1 propensity score-matched analyses were performed for
      (1) bilateral ITA versus single ITA and (2) bilateral ITA incorporating a free
      right ITA versus single ITA and RAs. Among the 912 patients with bilateral ITAs,
      those receiving an in situ right ITA to the left coronary system were compared
      with those receiving a free right ITA. RESULTS: In the propensity score-matched
      analysis comparing bilateral versus single ITAs (591 matched pairs), there were
      similar rates of 30-day mortality and deep sternal wound infection. Bilateral ITA
      use was associated with greater 15-year survival (79% +/- 3.9% vs 67% +/- 4.7%, P
      < .001). In the analysis between bilateral ITA incorporating a free right ITA
      versus single ITA + RAs (380 matched pairs), bilateral ITA use demonstrated
      comparable survival at 15 years (79% +/- 4.7% vs 67% +/- 5.7%, P = .09). Among
      patients receiving bilateral ITAs, comparison between in situ right ITA versus
      free right ITA recipients (206 matched pairs) revealed comparable 15-year
      survival (84% +/- 6.1% vs 79% +/- 6.7%, P = .13). Multivariable Cox regression
      found bilateral ITA use to be protective from mortality (hazard ratio, 0.73; 95%
      confidence interval, 0.59-0.90, P = .004). CONCLUSIONS: The use of bilateral ITAs
      as an in situ or free conduit is associated with greater survival and seems to
      offer a prognostic advantage over the use of only a single ITA supplemented by
      RAs. Therefore, all configurations of TAR are not equivalent.

PMID- 26211409
TI  - Molecular epidemiology of tuberculosis in Havana, Cuba, 2009.
AB  - OBJECTIVES: To estimate the proportion of tuberculosis cases attributable to
      recent transmission and the risk factors possibly associated with tuberculosis
      clustering. METHODS: Population-based study combining information from
      epidemiological investigation of tuberculosis cases notified to the National
      Tuberculosis Control Program in Havana, Cuba, in 2009 with the results of
      genotyping of Mycobacterium tuberculosis isolates with variable number tandem
      repeat of mycobacterial interspersed repetitive units (MIRU-VNTR) typing.
      RESULTS: Of 186 cases, 61 were genotyped: 33 patterns and five clusters with 19,
      7, 3, 2 and 2 cases were found. The proportion of cases due to recent
      transmission was 45% (95% confidence interval 33-58%). Routine contact
      investigation failed to identify a substantial number of epidemiological links. A
      history of living in a closed setting was strongly associated with clustering.
      CONCLUSIONS: The proportion of cases due to recent transmission in Havana in 2009
      is high. The existing control measures in closed settings should be strengthened.
      A study on a larger number of cases and for a longer time period should be
      carried out to obtain more precise estimates. Further studies on the utility and
      cost-effectiveness of the addition of molecular epidemiology techniques to
      support the progress towards tuberculosis elimination in Cuba, a low-incidence
      resource-limited setting, are also needed.

PMID- 26211407
TI  - 60,000 years of interactions between Central and Eastern Africa documented by
      major African mitochondrial haplogroup L2.
AB  - Mitochondrial DNA (mtDNA) haplogroup L2 originated in Western Africa but is
      nowadays spread across the entire continent. L2 movements were previously
      postulated to be related to the Bantu expansion, but L2 expansions eastwards
      probably occurred much earlier. By reconstructing the phylogeny of L2 (44 new
      complete sequences) we provide insights on the complex net of within-African
      migrations in the last 60 thousand years (ka). Results show that lineages in
      Southern Africa cluster with Western/Central African lineages at a recent time
      scale, whereas, eastern lineages seem to be substantially more ancient. Three
      moments of expansion from a Central African source are associated to L2: (1) one
      migration at 70-50 ka into Eastern or Southern Africa, (2) postglacial movements
      (15-10 ka) into Eastern Africa; and (3) the southward Bantu Expansion in the last
      5 ka. The complementary population and L0a phylogeography analyses indicate no
      strong evidence of mtDNA gene flow between eastern and southern populations
      during the later movement, suggesting low admixture between Eastern African
      populations and the Bantu migrants. This implies that, at least in the early
      stages, the Bantu expansion was mainly a demic diffusion with little
      incorporation of local populations. 

PMID- 26211410
TI  - Image reconstruction using a gradient impulse response model for trajectory
      prediction.
AB  - PURPOSE: Gradient imperfections remain a challenge in MRI, especially for
      sequences relying on long imaging readouts. This work aims to explore image
      reconstruction based on k-space trajectories predicted by an impulse response
      model of the gradient system. THEORY AND METHODS: Gradient characterization was
      performed twice with 3 years interval on a commercial 3 Tesla (T) system. The
      measured gradient impulse response functions were used to predict actual k-space
      trajectories for single-shot echo-planar imaging (EPI), spiral and variable-speed
      EPI sequences. Image reconstruction based on the predicted trajectories was
      performed for phantom and in vivo data. Resulting images were compared with
      reconstructions based on concurrent field monitoring, separate trajectory
      measurements, and nominal trajectories. RESULTS: Image reconstruction using model
      based trajectories yielded high-quality images, comparable to using separate
      trajectory measurements. Compared with using nominal trajectories, it strongly
      reduced ghosting, blurring, and geometric distortion. Equivalent image quality
      was obtained with the recent characterization and that performed 3 years prior.
      CONCLUSION: Model-based trajectory prediction enables high-quality image
      reconstruction for technically challenging sequences such as single-shot EPI and
      spiral imaging. It thus holds great promise for fast structural imaging and
      advanced neuroimaging techniques, including functional MRI, diffusion tensor
      imaging, and arterial spin labeling. The method can be based on a one-time system
      characterization as demonstrated by successful use of 3-year-old calibration
      data. Magn Reson Med 76:45-58, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26211412
TI  - Redox-Active NO(x) Ligands in Palladium-Mediated Processes.
AB  - This Minireview highlights the redox and non-innocent behavior of NO(x) ligands
      (x=1, 2, or 3) in selected Pd-mediated processes, for example, alkene and
      aromatic oxidation processes. A focus is placed on mechanistic understanding and
      linking recent transformations, such as C-H bond activation/functionalization and
      Wacker oxidation, with previous work on the functionalization of aromatics and
      alkenes by Pd(II) salts.

PMID- 26211411
TI  - Double Volume Exchange Transfusion in Severe Neonatal Sepsis.
AB  - OBJECTIVES: To study the efficacy and safety of double volume exchange
      transfusion (DVET) in neonates > 1000 g birth weight with severe sepsis. METHODS:
      Eighty-three neonates weighing >1000 g with severe sepsis were randomly assigned
      to DVET or standard therapy (ST) group. Primary outcome was mortality by 14 d
      from enrollment. RESULTS: A 21 % reduction in mortality, albeit non-significant,
      by 14 d from enrollment was observed in DVET group in comparison to ST group [RR:
      0.79 (95 % C.I 0.45-1.3); p 0.4]. A similar trend in mortality reduction was
      observed with early mortality and mortality by discharge in DVET group. No
      difference was observed in normalization of dysfunctional organs by 14 d.
      Cardiovascular and hematological system benefitted the most, followed by renal
      dysfunction with DVET. A significant improvement in post DVET IgG, IgA, IgM, C3
      and base deficit was observed. No serious adverse effects occurred following
      DVET. CONCLUSIONS: In neonates >1000 g with severe sepsis, DVET was associated
      with a trend towards decrease in mortality by 14 d from enrollment. A significant
      improvement in immunoglobulin and complement C3 levels and acid base status were
      observed following DVET. DVET is a safe procedure in severely sick and septic
      neonates.

PMID- 26211413
TI  - Genotype Diversity and Quasispecies Development of Helicobacter pylori in a
      Single Host.
AB  - Volume 68, no. 3, p. 176-180, 2015. Page 176, affiliation "(1) Foodborne and
      Waterborne Diseases Research Center, Tehran; (2)Basic and Molecular Epidemiology
      of Gastrointestinal Disorders Research Center, Tehran; (3)Department of
      Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran; and
      (4)Gastroenterology and Liver Diseases Research center, Research Institute for
      Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical
      Sciences, Tehran, Iran" should read "(1) Foodborne and Waterborne Diseases
      Research Center, Research Institute for Gastroenterology and Liver Diseases,
      Shahid Beheshti University of Medical Sciences, Tehran, Iran; (2)Basic and
      Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research
      Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of
      Medical Sciences, Tehran, Iran; (3)Department of Mycobacteriology and Pulmonary
      Research, Pasteur Institute of Iran, Tehran, Iran; and (4)Gastroenterology and
      Liver Diseases Research Center, Research Institute for Gastroenterology and Liver
      Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran".

PMID- 26211414
TI  - Comparative analysis of driver's brake perception-reaction time at signalized
      intersections with and without countdown timer using parametric duration models.
AB  - Countdown timers display the time left on the current signal, which makes drivers
      be more ready to react to the phase change. However, previous related studies
      have rarely explored the effects of countdown timer on driver's brake perception
      reaction time (BPRT) to yellow light. The goal of this study was therefore to
      characterize and model driver's BPRT to yellow signal at signalized intersections
      with and without countdown timer. BPRT data for "first-to-stop" vehicles after
      yellow onset within the transitional zone were collected through on-site
      observation at six signalized intersections in Harbin, China. Statistical
      analysis showed that the observed 15th, 50th, and 85th percentile BPRTs without
      countdown timer were 0.52, 0.84, and 1.26s, respectively. The observed 15th,
      50th, and 85th percentile BPRTs with countdown timer were 0.32, 1.20, and 2.52s,
      respectively. Log-logistic distribution appeared to best fit the BPRT without
      countdown timer, while Weibull distribution seemed to best fit the BPRT with
      countdown timer. After that, a Log-logistic accelerated failure time (AFT)
      duration model was developed to model driver's BPRT without countdown timer,
      whereas a Weibull AFT duration model was established to model driver's BPRT with
      countdown timer. Three significant factors affecting the BPRT identified in both
      AFT models included yellow-onset distance from the stop line, yellow-onset
      approach speed, and deceleration rate. No matter whether the presence of
      countdown timer or not, BPRT increased as yellow-onset distance to the stop line
      or deceleration rate increased, but decreased as yellow-onset speed increased.
      The impairment of driver's BPRT due to countdown timer appeared to increase with
      yellow-onset distance to the stop line or deceleration rate, but decrease with
      yellow-onset speed. An increase in driver's BPRT because of countdown timer may
      induce risky driving behaviors (i.e., stop abruptly, or even violate traffic
      signal), revealing a weakness of countdown timer in traffic safety aspect. 

PMID- 26211415
TI  - A pilot randomized controlled trial of mindfulness-based stress reduction for
      caregivers of family members with dementia.
AB  - OBJECTIVES: The majority of care for those with Alzheimer's disease and other age
      related dementias is provided in the home by family members. To date, there is no
      consistently effective intervention for reducing the significant stress burden of
      many family caregivers. The present pilot randomized controlled trial tested the
      efficacy of an adapted, eight-week mindfulness-based stress reduction (MBSR)
      program, relative to a near structurally equivalent, standard social support (SS)
      control condition for reducing caregiver stress and enhancing the care giver
      recipient relationship. METHOD: Thirty-eight family caregivers were randomized to
      MBSR or SS, with measures of diurnal salivary cortisol, and perceived stress,
      mental health, experiential avoidance, caregiver burden, and relationship quality
      collected pre- and post-intervention and at three-month follow-up. RESULTS: MBSR
      participants reported significantly lower levels of perceived stress and mood
      disturbance at post-intervention relative to SS participants. At three-month
      follow-up, participants in both treatment conditions reported improvements on
      several psychosocial outcomes. At follow-up, there were no condition differences
      on these outcomes, nor did MBSR and SS participants differ in diurnal cortisol
      response change over the course of the study. CONCLUSION: Both MBSR and SS showed
      stress reduction effects, and MBSR showed no sustained neuroendocrine and
      psychosocial advantages over SS. The lack of treatment condition differences
      could be attributable to active ingredients in both interventions, and to
      population-specific and design factors.

PMID- 26211416
TI  - Prenatal diagnosis of inguinoscrotal hernia associated with bowel dilatation: a
      pathogenetic hypothesis.

PMID- 26211417
TI  - BODIPY-doped silica nanoparticles with reduced dye leakage and enhanced singlet
      oxygen generation.
AB  - Photodynamic therapy (PDT) is a promising modality for cancer treatment. The
      essential element in PDT is the photosensitizer, which can be excited by light of
      a specific wavelength to generate cytotoxic oxygen species (ROS) capable of
      killing tumor cells. The effectiveness of PDT is limited in part by the low yield
      of ROS from existing photosensitizers and the unwanted side effects induced by
      the photosensitizers toward normal cells. Thus the design of nanoplatforms with
      enhanced PDT is highly desirable but remains challenging. Here, we developed a
      heavy atom (I) containing dipyrromethene boron difluoride (BODIPY) dye with a
      silylated functional group, which can be covalently incorporated into a silica
      matrix to form dye-doped nanoparticles. The incorporated heavy atoms can enhance
      the generation efficiency of ROS. Meanwhile, the covalently dye-encapsulated
      nanoparticles can significantly reduce dye leakage and subsequently reduce
      unwanted side effects. The nanoparticles were successfully taken up by various
      tumor cells and showed salient phototoxicity against these cells upon light
      irradiation, demonstrating promising applications in PDT. Moreover, the
      incorporated iodine atom can be replaced by a radiolabeled iodine atom (e.g., I
      124, I-125). The resulting nanoparticles will be good contrast agents for
      positron emission tomography (PET) imaging with their PDT functionality retained.

PMID- 26211418
TI  - 5-aminomethyloxazolidine-2,4-dione hybrid alpha/beta-dipeptide scaffolds as
      inductors of constrained conformations: Applications to the synthesis of integrin
      antagonists.
AB  - Peptidomimetics represent an attractive starting point for drug discovery
      programs; in particular, peptidomimetics that result from the incorporation of a
      heterocycle may take advantage of increased enzymatic stability and higher
      ability to reproduce the bioactive conformations of the parent peptides,
      resulting in enhanced therapeutic potential. Herein, we present mimetics of the
      alpha4beta1 integrin antagonist BIO1211 (MPUPA-Leu-Asp-Val-Pro-OH), containing a
      aminomethyloxazolidine-2,4-dione scaffold (Amo). Interestingly, the retro
      sequences PhCOAsp(OH)-Amo-APUMP including either (S)- or (R)-configured Amo
      displayed significant ability to inhibit the adhesion of alpha4beta1 integrin
      expressing cells, and remarkable stability in mouse serum. Possibly, the
      conformational bias exerted by the Amo scaffold determined the affinity for the
      receptors. These peptidomimetics could be of interest for the development of
      small-molecule agents effective against inflammatory processes and correlated
      autoimmune diseases.

PMID- 26211419
TI  - Safety, immunization coverage and determinants of a new kind of Hepatitis B
      vaccine firstly applied in Ningbo, China.
AB  - Evaluate safety and immunization coverage of a new kind of recombinant Hepatitis
      B vaccine (HepB) in Ningbo city, China. Two groups were carried out in 2 of 11
      randomly selected countries in Ningbo in 2009. All of the infants born from July
      1 to December 31, 2009 were enrolled as subjects and received 3 doses of HepB at
      0, 1, 6 month. Control group (N = 3452) received current HepB derived from
      Saccharomyces Cerevisiae Yeast (HepB made by recombinant DNA techniques in
      Saccharomyces Cerevisiae Yeast, HepB-SCY; 5 MUg/0.5 ml per dose) and experimental
      group (N = 5104) received the new kind of HepB derived from Hansenula polymorpha
      Yeast (HepB made by recombinant DNA techniques in Hansenula polymorpha Yeast,
      HepB-HPY; 10 MUg/0.5 ml per dose). 3-dose and timely birth dose (TBD) coverage
      were available and compared between 2 groups. Standard structured questionnaires
      were applied to record information from parents and hospitals for selecting
      determinants of coverage. The data were analyzed using stepwise multiple logistic
      regression models. After each dose, HepB-related adverse events (AEs) and recta
      temperature were recorded for 7 days. 3-dose coverage in control group (89.98%)
      was higher than that in experimental group (chi2 = 575.1173, P < 0.0001). TBD
      coverage in control and experimental group were 98.41% and 98.53%, respectively.
      No statistically significant difference in TBD coverage was found between 2
      groups (chi2 = 0.0623, P = 0.8029). A total of 9 local AEs were reported, 4 for
      control group and 5 for experimental group. The percentages of subjects reporting
      AEs were similar across the 2 vaccination groups. No serious or immediate
      reactions were found in this study. From logistic models, receiving 10 MUg
      vaccine (odds ratio [OR]:0.38; 95% confidence interval [95%CI]: 0.34-0.44) and
      mother migrating from other cities (OR: 0.45; 95%CI: 0.42-0.47) were the
      determinants for non-acceptance of 3 doses of HepB; infants born from low grade
      hospitals and native mothers contributed to administrate the TBD.

PMID- 26211420
TI  - Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma-Past, Present,
      and Future.
AB  - Esophageal adenocarcinoma is the fastest rising cancer in the United States. It
      develops from long-standing gastroesophageal reflux disease which affects >20% of
      the general population. It carries a very poor prognosis with 5-year survival
      <20%. The disease is known to sequentially progress from reflux esophagitis to a
      metaplastic precursor, Barrett's esophagus and then onto dysplasia and esophageal
      adenocarcinoma. However, only few patients with reflux develop Barrett's
      esophagus and only a minority of these turn malignant. The reason for this
      heterogeneity in clinical progression is unknown. To improve patient management,
      molecular changes which facilitate disease progression must be identified. Animal
      models can provide a comprehensive functional and anatomic platform for such a
      study. Rats and mice have been the most widely studied but disease homology with
      humans has been questioned. No animal model naturally simulates the inflammation
      to adenocarcinoma progression as in humans, with all models requiring surgical
      bypass or destruction of existing antireflux mechanisms. Valuable properties of
      individual models could be utilized to holistically evaluate disease progression.
      In this review paper, we critically examined the current animal models of
      Barrett's esophagus, their differences and homologies with human disease and how
      they have shaped our current understanding of Barrett's carcinogenesis. 

PMID- 26211421
TI  - Effect of corticosteroids on articular cartilage: have animal studies said
      everything?
AB  - Intra-articular (IA) corticosteroids (CS) have been used in the treatment of
      osteoarthritis for many years, although their effects on articular cartilage are
      not fully understood. To identify whether previous animal studies have provided
      enough evidence about the effects of CS, we undertook a systematic review that
      identified 35 relevant in vivo animal experimental studies between 1965 and 2014
      assessing the effects of CS on either normal cartilage, or in either induced
      osteoarthritis (OA) or synovitis. The quality of the methodology was assessed.
      Deleterious effects, both structural and biochemical, have mainly been reported
      in rabbits and are associated with frequent administration of CS, sometimes at
      high dose and with systemic side effects. In dogs, four identified studies
      concluded that there were beneficial effects with methylprednisolone acetate
      (MPA) and triamcinolone hexacetonide therapy. In horses, MPA was mostly
      deleterious, while triamcinolone acetonide had positive effects in one study
      highly rated at quality assessment. However, many methodological weaknesses have
      been identified, such as the lack of pharmacokinetic and pharmocodynamics data
      and the large variation in doses between studies, the limited selection criteria
      at baseline, the absence of blinding, and the lack of statistics or appropriate
      controls for testing the effects of the vehicle of the drug. Those methodological
      weaknesses weaken the conclusions of numerous studies that assess beneficial or
      deleterious effects of CS on articular cartilage. Animal studies have not yet
      provided definitive data, and further research is required into the role of CS in
      articular pathobiology. 

PMID- 26211422
TI  - Cervical and scapulothoracic stabilization exercises with and without connective
      tissue massage for chronic mechanical neck pain: A prospective, randomised
      controlled trial.
AB  - This study was planned to assess and compare the effectiveness of cervical and
      scapulothoracic stabilization exercise treatment with and without connective
      tissue massage (CTM) on pain, anxiety, and the quality of life in patients with
      chronic mechanical neck pain (MNP). Sixty patients with chronic MNP (18-65 years)
      were recruited and randomly allocated into stabilization exercise with (Group 1,
      n = 30) and without the CTM (Group 2, n = 30). The program was carried out for 12
      sessions, 3 days/week in 4 weeks. Pain intensity with Visual Analog Scale,
      pressure pain threshold with digital algometer (JTech Medical Industries, ZEVEX
      Company), level of anxiety with Spielberger State Trait Anxiety Inventory, and
      quality of life with Short Form-36 were evaluated before and after the treatment.
      After the program, pain intensity and the level of anxiety decrease, physical
      health increase in Group 1 and 2 were found (p < 0.05). Pressure pain threshold
      and mental health increase were detected in only Group 1 (p < 0.05). The
      intergroup comparison showed that significant difference in pain intensity at
      night, pressure pain threshold, state anxiety and mental health were seen in
      favor of Group 1 (p < 0.05). The study suggested that stabilization exercises
      with and without the CTM might be a useful treatment for patients with chronic
      MNP. However, stabilization exercises with CTM might be superior in improving
      pain intensity at night, pressure pain threshold, state anxiety and mental health
      compared to stabilization exercise alone. 

PMID- 26211423
TI  - Effect of body mass and midsole hardness on kinetic and perceptual variables
      during basketball landing manoeuvres.
AB  - This study investigated the effects of body mass and shoe midsole hardness on
      kinetic and perceptual variables during the performance of three basketball
      movements: (1) the first and landing steps of layup, (2) shot-blocking landing
      and (3) drop landing. Thirty male basketball players, assigned into "heavy" (n =
      15, mass 82.7 +/- 4.3 kg) or "light" (n = 15, mass 63.1 +/- 2.8 kg) groups,
      performed five trials of each movement in three identical shoes of varying
      midsole hardness (soft, medium, hard). Vertical ground reaction force (VGRF)
      during landing was sampled using multiple wooden-top force plates. Perceptual
      responses on five variables (forefoot cushioning, rearfoot cushioning, forefoot
      stability, rearfoot stability and overall comfort) were rated after each movement
      condition using a 150-mm Visual Analogue Scale (VAS). A mixed factorial analysis
      of variance (ANOVA) (Body Mass * Shoe) was applied to all kinetic and perceptual
      variables. During the first step of the layup, the loading rate associated with
      rearfoot contact was 40.7% higher in the "heavy" than "light" groups (P = .014)
      and 12.4% higher in hard compared with soft shoes (P = .011). Forefoot peak VGRF
      in a soft shoe was higher (P = .011) than in a hard shoe during shot-block
      landing. Both "heavy" and "light" groups preferred softer to harder shoes.
      Overall, body mass had little effect on kinetic or perceptual variables. 

PMID- 26211424
TI  - Fugacity and activity analysis of the bioaccumulation and environmental risks of
      decamethylcyclopentasiloxane (D5).
AB  - As part of an initiative to evaluate commercial chemicals for their effects on
      human and environmental health, Canada recently evaluated
      decamethylcyclopentasiloxane (D5; CAS no. 541-02-06), a high-volume production
      chemical used in many personal care products. The evaluation illustrated the
      challenges encountered in environmental risk assessments and the need for the
      development of better tools to increase the weight of evidence in environmental
      risk assessments. The present study presents a new risk analysis method that
      applies thermodynamic principles of fugacity and activity to express the results
      of field monitoring and laboratory bioaccumulation and toxicity studies in a
      comprehensive risk analysis that can support risk assessments. Fugacity and
      activity ratios of D5 derived from bioaccumulation measures indicate that D5 does
      not biomagnify in food webs, likely because of biotransformation. The fugacity
      and activity analysis further demonstrates that reported no-observed-effect
      concentrations of D5 normally cannot occur in the environment. Observed
      fugacities and activities in the environment are, without exception, far below
      those corresponding with no observed effects, in many cases by several orders of
      magnitude. This analysis supports the conclusion of the Canadian Board of Review
      and the Minister of the Environment that D5 does not pose a danger to the
      environment. The present study further illustrates some of the limitations of a
      persistence-bioaccumulation-toxicity-type criteria-based risk assessment approach
      and discusses the merits of the fugacity and activity approach to increase the
      weight of evidence and consistency in environmental risk assessments of
      commercial chemicals.

PMID- 26211425
TI  - Utilization of Kidneys With Acute Kidney Injury in the Extended Criteria Donor
      Setting.

PMID- 26211426
TI  - Liposomes Size Engineering by Combination of Ethanol Injection and Supercritical
      Processing.
AB  - Supercritical fluid extraction using a high-pressure packed tower is proposed not
      only to remove the ethanol residue from liposome suspensions but also to affect
      their size and distribution leading the production of nanosomes. Different
      operating pressures, temperatures, and gas to liquid ratios were explored and
      ethanol was successfully extracted up to a value of 400 ppm; liposome size and
      distribution were also reduced by the supercritical processing preserving their
      integrity, as confirmed by Z-potential data and Trasmission Electron Microscopy
      observations. Operating at 120 bar and 38 degrees C, nanosomes with a mean
      diameter of about 180 +/- 40 nm and good storage stability were obtained. The
      supercritical processing did not interfere on drug encapsulation, and no loss of
      entrapped drug was observed when the water-soluble fluorescein was loaded as a
      model compound. Fluorescein encapsulation efficiency was 30% if pure water was
      used during the supercritical extraction as processing fluid; whereas an
      encapsulation efficiency of 90% was obtained if the liposome suspension was
      processed in water/fluorescein solution. The described technology is easy to
      scale up to an industrial production and merge in one step the solvent
      extraction, liposome size engineering, and an excellent drug encapsulation in a
      single operation unit.

PMID- 26211427
TI  - Impact of a Clinical Pharmacy Specialist in an Emergency Department for Seniors.
AB  - STUDY OBJECTIVE: This study assesses outcomes associated with the implementation
      of an emergency department (ED) for seniors in which a clinical pharmacy
      specialist, with specialized geriatric training that included medication
      management training, is a key member of the ED care team. METHODS: This was a
      retrospective cohort analysis of patients aged 65 years or older who presented at
      an ED between November 1, 2012, and May 31, 2013. Three groups of seniors were
      assessed: treated by the clinical pharmacy specialist in the ED for seniors,
      treated in the ED for seniors but not by the clinical pharmacy specialist, and
      not treated in the ED for seniors. Outcomes included rates of an ED return visit,
      mortality and hospital admissions, and follow-up total health care costs.
      Multivariable regression modeling was used to adjust for any potential
      confounders in the associations between groups and outcomes. RESULTS: A total of
      4,103 patients were included, with 872 (21%) treated in the ED for seniors and
      342 (39%) of these treated by the clinical pharmacy specialist. Groups were well
      matched overall in patient characteristics. Patients who received medication
      review and management by the clinical pharmacy specialist did not experience a
      reduction in ED return visits, mortality, cost of follow-up care, or hospital
      admissions compared with the other groups. Of the patients treated by the
      clinical pharmacy specialist, 154 (45.0%) were identified as having at least 1
      medication-related problem. CONCLUSION: Although at least 1 medication-related
      problem was identified in almost half of patients treated by the clinical
      pharmacy specialist in the ED for seniors, incorporation of a clinical pharmacy
      specialist into the ED staff did not improve clinical outcomes.

PMID- 26211428
TI  - Are Oral Antibiotics as Effective as a Combination of Intravenous and Oral
      Antibiotics for Kidney Infections in Children?

PMID- 26211429
TI  - The seed of the Amazonian fruit Couepia bracteosa exhibits higher scavenging
      capacity against ROS and RNS than its shell and pulp extracts.
AB  - Among the large number of scientifically unstudied fruits from the Amazonia
      biome, Couepia bracteosa acts as an interesting source of bioactive compounds,
      such as phenolic compounds and carotenoids, which may be used for protecting
      human health against oxidative damage. For the first time, the phenolic compounds
      and carotenoids in extracts obtained from the pulp, shell and seeds of C.
      bracteosa fruits are reported, as well as their in vitro scavenging capacities
      against some reactive oxygen species (ROS) and reactive nitrogen species (RNS).
      The shell extract presented the highest phenolic compound and carotenoid contents
      (5540 and 328 MUg per g extract, dry basis, respectively), followed by the pulp
      and seed extracts. The major phenolic compound was acacetin sulphate (one methoxy
      and two OH groups) (62%) in the shells; however, only seeds presented apigenin
      sulphate (three OH groups), in which it was the major compound (44%). The high
      content of apigenin sulphate may explain why the seed extract had the highest
      scavenging efficiency against all tested ROS/RNS among the studied extracts.
      Regarding carotenoids, all-trans-neochrome (17%) and all-trans-beta-carotene
      (16%) were the major carotenoids in the pulp extracts, while all-trans-lutein
      (44%) was the most prevalent in the shell extracts and all-trans-alpha-carotene
      (32%) and all-trans-beta-carotene (29%) were the major ones in the seed extracts.

PMID- 26211430
TI  - Evaporative cooling in late-gestation Murrah buffaloes potentiates immunity
      around transition period and overcomes reproductive disorders.
AB  - The objective of the study was to observe the effect of evaporative cooling
      during late gestation on immunity around the transition period and the probable
      outcome on reproductive disorders in Murrah buffaloes. Sixteen pregnant dry
      Murrah buffaloes at 60 days prepartum were selected and divided into two groups
      of eight animals each. Group 1 buffaloes remained without the provision of
      cooling, whereas the second group of buffaloes was managed under fans and mist
      cooling during the dry period. After parturition, all the animals were managed
      under evaporative cooling. Dry matter intake was significantly (P < 0.05) higher
      in cooled relative to noncooled animals at -15, 0, and +20 days of parturition.
      Cortisol and prolactin levels were significantly (P < 0.05) higher in noncooled
      relative to cooled animals at -15 and 0 days of parturition. However, prolactin
      was significantly (P < 0.05) higher in cooled animals at +20 days. Messenger RNA
      expression of prolactin receptor gene (PRL-R) was upregulated and suppressor of
      cytokine signaling gene 1 (SOCS-1) was downregulated in cooled animals at -20, 0,
      and +20 days of parturition. Tumor necrosis factor alpha and interleukin 4 levels
      remained significantly (P < 0.05) higher in cooled animals at -20, 0, and +20
      days of parturition. Interleukin 6 was significantly (P < 0.05) lower in cooled
      animals at -20 and 0 days. Interferon gamma levels were significantly higher at 
      20 and +20 days of parturition in cooled relative to noncooled animals. The
      reproductive disorders such as retention of placenta, metritis, and endometritis
      occurred at the rate of 37.25%, 25%, and 12.25% in the noncooled group, whereas
      only retention of placenta was observed in the cooled (12.5%) group.

PMID- 26211431
TI  - Dysregulation of cardiac autonomic function in offspring exposed to alcohol
      during antenatal period.
AB  - Several lines of investigations have shown the deleterious effect of an alcohol
      on the autonomic nervous system. Recent evidence shows that infants exposed to
      alcohol during the antenatal period displayed aberration in the cardiac autonomic
      function after the birth. However, there is dearth of literature on the long term
      influence of antenatal alcohol exposure. In this study we measured the cardiac
      autonomic functions in children who were exposed to alcohol in the antenatal
      period and compared them with non-exposed control children. Twenty eight children
      (age: 9+/-2 years) in the antenatal alcohol exposed group and age, gender matched
      30 non exposed healthy volunteers as a control (age: 10+/-2 years) were
      recruited. Electrocardiogram was recorded in all subjects at rest in the supine
      position. HRV parameters were analyzed in the time and frequency domains using
      customized software. The average heart rate was similar between both the groups.
      There was no statistical significant difference in the time domain measures
      between the groups. However, the low frequency power, normalized units and low
      frequency to high frequency ratio were significantly higher in the antenatal
      alcohol exposed children compared to the controls. This suggests sympathetic
      predominance in children who were exposed to alcohol in the antenatal period. In
      this study we provide evidence for the deleterious long lasting effect of
      antenatal exposure of alcohol on cardiac autonomic regulation. Further
      prospective studies are needed to confirm the causal relationship between
      antenatal alcohol exposure and autonomic dysregulation. 

PMID- 26211432
TI  - Annurca peel extract: from the chemical composition, through the functional
      activity, to the formulation and characterisation of a topical oil-in-water
      emulsion.
AB  - The aim of this study was to produce a hydro-alcoholic safe antioxidant Malus
      pumila Miller cv Annurca peel extract (APE) useful as functional ingredient in an
      oil-in-water emulsion. Results showed that APE contains a hydroxycinnamic acid
      (chlorogenic acid), flavonol glycosides (quercetin derivatives) and a
      dihydrochalcone, phloridzin (phloretin-2-O-glucoside). The isoquercitrin
      (quercetin-3-O-glucoside) content was quantified in 0.3% w/w of extract. APE
      showed a significant and concentration-dependent free-radical scavenging activity
      correlated to its polyphenols content. No cytotoxic effect was observed in
      primary human epidermal keratinocyte adults and dermal fibroblast cell lines. The
      formulative approach led to produce a stable emulsion able to load a high amount
      of APE, up to 6.0% w/w. The homogenous distribution of APE in the emulsion was
      clearly demonstrated by fluorescence microscopy analysis. The emulsion resulted
      able to enhance the in vitro release rate of APE through synthetic membranes with
      respect to the raw material. 

PMID- 26211433
TI  - Gender differences in the neural network of facial mimicry of smiles--An rTMS
      study.
AB  - Under theories of embodied emotion, exposure to a facial expression triggers
      facial mimicry. Facial feedback is then used to recognize and judge the perceived
      expression. However, the neural bases of facial mimicry and of the use of facial
      feedback remain poorly understood. Furthermore, gender differences in facial
      mimicry and emotion recognition suggest that different neural substrates might
      accompany the production of facial mimicry, and the processing of facial
      feedback, in men and women. Here, repetitive transcranial magnetic stimulation
      (rTMS) was applied to the right primary motor cortex (M1), the right primary
      somatosensory cortex (S1), or, in a control condition, the vertex (VTX). Facial
      mimicry of smiles and emotion judgments were recorded in response to video clips
      depicting changes from neutral or angry to happy facial expressions. While in
      females rTMS over M1 and S1 compared to VTX led to reduced mimicry and, in the
      case of M1, delayed detection of smiles, there was no effect of TMS condition for
      males. We conclude that in female participants M1 and S1 play a role in the
      mimicry and in the use of facial feedback for accurate processing of smiles. 

PMID- 26211434
TI  - The importance of neuroscience in understanding bilingual cognitive control.

PMID- 26211435
TI  - The neural network associated with lexical-semantic knowledge about social
      groups.
AB  - A person can be appraised as an individual or as a member of a social group. In
      the present study we tested whether the knowledge about social groups is
      represented independently of the living and non-living things. Patients with
      frontal and temporal lobe tumors involving either the left or the right
      hemisphere performed three tasks--picture naming, word-to-picture matching and
      picture sorting--tapping the lexical semantic knowledge of living things, non
      living things and social groups. Both behavioral and voxel-based lesion-symptom
      mapping (VLSM) analyses suggested that social groups might be represented
      differently from other categories. VLSM analysis carried out on naming errors
      revealed that left-lateralized lesions in the inferior frontal gyrus, amygdala,
      insula and basal ganglia were associated with the lexical-semantic processing of
      social groups. These findings indicate that the social group representation may
      rely on areas associated with affective processing.

PMID- 26211436
TI  - Preharvest temperature affects chilling injury in dessert bananas during storage.
AB  - BACKGROUND: The effect of temperature on chilling injury during fruit growth was
      studied in a new banana hybrid CIRAD925 in which seasonal variability in chilling
      susceptibility was observed when fruits were stored at 13  degrees C. RESULTS:
      The relationship between the response to chilling (presence/absence) and the
      temperature during banana fruit growth was examined with a logistic regression
      model. An explanatory variable XN , P was defined as the mean temperature during
      a period, expressed in weeks, which began N week(s) after flowering and lasted P
      week(s). The model was calibrated with 143 bunches with a green life of 30 +/- 5
      days and validated with 156 bunches grown in six plots under different growing
      conditions. Chilling injury was best predicted by the mean temperature during the
      period beginning 1 week after flowering and lasting 5 weeks (X1,5 ). Above a mean
      temperature of 24.1  degrees C in the period concerned, banana fruits had a 95%
      probability of chilling injury at 13  degrees C. Below a temperature of 23.4 
      degrees C, banana fruits only had a 5% probability of chilling injury.
      CONCLUSION: The results provide a tool to predict chilling susceptibility in
      banana fruit whatever the thermal conditions in tropical regions. (c) 2015
      Society of Chemical Industry.

PMID- 26211437
TI  - Synthesis, structure, and reactivity of iridium perfluorocarbene complexes: regio
      and stereo-specific addition of HCl across a metal carbon double bond.
AB  - Reductive activation of an alpha-fluorine in the perfluoroalkyl complexes
      Cp*(L)(i)Ir-CF2RF using Mg/graphite leads to perfluorocarbene complexes
      Cp*(L)Ir[double bond, length as m-dash]CFRF (L = CO, PMe3; RF = CF3, C2F5, C6F5).
      New complexes E-Cp*(PMe3)Ir[double bond, length as m-dash]CFC2F5 and E
      Cp*(CO)Ir[double bond, length as m-dash]CFC6F5 have been characterized by single
      crystal X-ray diffraction studies, and a comparison of metric parameters with
      previously reported analogues is reported. Experimental NMR and computational DFT
      (B3LYP/LACV3P**++) studies agree that for Ir[double bond, length as m-dash]CFRF
      complexes (RF = CF3, CF2CF3) the thermodynamic preference for the E or Z isomer
      depends on the steric requirements of ligand L; when L = CO the Z-isomer (F cis
      to Cp*) is preferred and for L = PMe3 the E-isomer is preferred. When reduction
      of the precursors is carried out in the dark the reaction is completely selective
      to produce E- or Z-isomers. Exposure of solutions of these compounds to ambient
      light results in slow conversion to a photostationary non-equilibrium mixture of
      E and Z isomers. In the dark, these E/Z mixtures convert thermally to their
      preferred E or Z equilibrium geometries in an even slower reaction. A study of
      the temperature dependent kinetics of this dark transformation allows
      DeltaG(?)298 for rotation about the Ir[double bond, length as m-dash]CFCF3 double
      bond to be experimentally determined as 25 kcal mol(-1); a DFT/B3LYP/LACV3P**++
      calculation of this rotation barrier is in excellent agreement (27 kcal mol(-1))
      with the experimental value. Reaction of HCl with toluene solutions of
      Cp*(L)Ir[double bond, length as m-dash]CFRF (L = CO, PMe3) or Cp*(CO)Ir[double
      bond, length as m-dash]C(CF3)2 at low temperature resulted in regiospecific
      addition of HCl across the metal carbon double bond, ultimately yielding
      Cp*(L)Ir(CHFRF)Cl and Cp*(CO)Ir[CH(CF3)2]Cl. Reaction of HCl with single E or Z
      diastereomers of Cp*(L)Ir[double bond, length as m-dash]CFRF gives stereospecific
      cis-addition to give single diastereomers of Cp*Ir(L)(CHFRF)Cl; addition of HCl
      to several different E/Z ratios of Cp*(L)Ir[double bond, length as m-dash]CFRF
      affords ratios of diastereomeric products Cp*(L)Ir(CHFRF)Cl identical to the
      original ratio of starting material isomers. The addition of HCl is therefore
      demonstrated to be unambiguously regio- and stereo-specific. The observed product
      regiochemistry of addition of HCl to Ir[double bond, length as m-dash]CF2,
      Ir[double bond, length as m-dash]CFRF, and Ir[double bond, length as m
      dash]C(CF3)2 ligands is the same and is not dependent on the ground state energy
      preference (singlet or triplet) for the free perfluorocarbene. DFT calculations
      on model HCl addition reactions indicate that this regiochemistry is strongly
      preferred thermodynamically, but predict that in H(delta+)-Cl(delta-) addition to
      Cp(PH3)Ir[double bond, length as m-dash]CF2, H(delta+) attack at Ir has a lower
      energy transition state, while for Cp(PH3)Ir[double bond, length as m-dash]CFCF3
      and Cp(PH3)Ir[double bond, length as m-dash]C(CF3)2, H(delta+) attack at C is the
      kinetically preferred pathway. The carbene carbon atoms in Ir[double bond, length
      as m-dash]CFCF3 and Ir[double bond, length as m-dash]C(CF3)2 complexes are
      unambiguously basic towards HCl, while in the Ir[double bond, length as m
      dash]CF2 analogues the carbene carbon is less basic than its Ir partner, and the
      eventual regiochemistry of HCl addition arises from thermodynamic control. 

PMID- 26211438
TI  - Systematic review of optical coherence tomography usage in the diagnosis and
      management of basal cell carcinoma.
AB  - Optical coherence tomography (OCT) is a noninvasive imaging tool used in vivo in
      real time for diagnosis, treatment delineation and monitoring of basal cell
      carcinoma (BCC). Features of BCC on OCT have been widely described and reviewed.
      However, the diagnostic accuracy of OCT in these various applications is unclear.
      We systematically reviewed the literature to assess the accuracy of OCT in
      diagnosis and management of BCC using the Embase and Medline databases. In total
      179 unique references were identified in the initial search, of which 22 studies
      with 556 histologically proven BCCs were eligible. Assessment of the quality of
      eligible studies was undertaken using the STROBE criteria. Data extraction and
      quality assessment were performed independently by the two authors. This
      systematic review provides an overview of the clinical applications of OCT in the
      diagnosis and management of BCC. OCT has been suggested to be useful in the
      diagnosis, treatment planning and treatment monitoring of BCC. As the technology
      improves and its utility increases, further studies with good methodological
      quality will be needed to implement OCT into daily practice. 

PMID- 26211439
TI  - Postoperative drain amylase predicts pancreatic fistula in pancreatic surgery: A
      systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: This study to evaluate the utility of drain fluid
      amylase as a predictor of PF in patients undergoing pancreatic surgery based on
      the International Study Group of Pancreatic Fistula definitions of pancreatic
      fistula. METHODS: A comprehensive search was carried out using Pubmed (Medline),
      Embase, Web of science and Cochrane database for clinical trials, which studied
      DFA as a diagnostic marker for pancreatic fistula after pancreatic surgery.
      Sensitivity, specificity and the diagnostic odds ratios with 95% confidence
      interval were calculated for each study. Summary receiver-operating curves were
      conducted and the area under the curve was evaluated. RESULTS: A total of 10
      studies were included. The pooled sensitivity and specificity of drain fluid
      amylase Day 1 for the diagnosis of postoperative pancreatic fistula were 81% and
      87%, respectively (area under the curve was 0.897, diagnostic odds ratios was
      16.83 and 95%CI was 12.66-22.36), the pooled sensitivity and specificity of drain
      fluid amylase Day 3 for the diagnosis of postoperative pancreatic fistula were
      56% and 79%, respectively (area under the curve was 0.668, diagnostic odds ratios
      was 3.26 and 95%CI was 1.83-5.82) CONCLUSIONS: The drain fluid amylase Day 1,
      instead of drain fluid amylase Day 3, may be a useful criterion for the early
      identification of postoperative pancreatic fistula, and a value of drain fluid
      amylase Day 1 over than 1300 U/L was a risk factor of pancreatic fistula. And the
      diagnostic accuracy and the proposed cut-off levels of drain fluid amylase Day 1
      in predicting the postoperative pancreatic fistula will have to be validated by
      multicenter prospective studies.

PMID- 26211440
TI  - Feedlot Processing and Arrival Cattle Management.
AB  - Acclimating newly arrived cattle in a feedlot setting can increase cattle
      confidence, reduce stress, improve immune function, and increase cattle well
      being. Understanding cattle instincts and using low-stress handling techniques
      teaches cattle to trust their caregivers and work efficiently for them throughout
      the feeding period. These techniques should be applied with newly arrived cattle
      when they are unloaded, moved from the holding pen to the home pen, and handled
      inside the home pen. Low-stress handling during processing and a sound processing
      protocol based on cattle history and proper risk assessment can improve cattle
      health from the start of the feeding period. 

PMID- 26211441
TI  - Electrocatalysis of NADH oxidation using electrochemically activated fluphenazine
      on carbon nanotube electrode.
AB  - Electrocatalytic determination of NADH using a hybrid surface-modified electrode
      with multi-wall carbon nanotubes (MWCNTs) and a novel electrogenerated redox
      mediator is described. The redox mediator precursor - fluphenazine (Flu) was
      adsorbed on MWCNT-modified glassy carbon (GC) electrode which was then subjected
      to electrochemical activation in 0.1 M H2SO4 using cyclic voltammetry (CV) over a
      range of potentials -0.2 to 1.5 V vs. Ag/AgCl (6 scans at 100 mV s(-1)). Cyclic
      voltammograms of Flu indicated the formation of a stable electroactive material
      presenting one reversible redox couple at the formal potential of -0.115 vs.
      Ag/AgCl in a phosphate buffer (pH7.0) as a supporting electrolyte. The peaks
      increased linearly with increasing scan rate indicating electroactive molecules
      anchored to the electrode surface. The GC/MWCNT/Flu electrode efficiently
      catalyzed the oxidation of NADH with a decrease in the overpotential of about 600
      mV and 150 mV compared to the bare GC and GC/MWCNT electrode, respectively. This
      modified electrode was successfully used as the working electrode in the
      chronoamperometric analysis. The peak current response to NADH was linear over
      its concentration range from 15 MUM to 84 MUM, and correlation coefficient 0.998.
      The limits of detection (5 MUM) and quantitation (15 MUM) were evaluated.

PMID- 26211442
TI  - Nanoscale optical positioning of single quantum dots for bright and pure single
      photon emission.
AB  - Self-assembled, epitaxially grown InAs/GaAs quantum dots (QDs) are promising
      semiconductor quantum emitters that can be integrated on a chip for a variety of
      photonic quantum information science applications. However, self-assembled growth
      results in an essentially random in-plane spatial distribution of QDs, presenting
      a challenge in creating devices that exploit the strong interaction of single QDs
      with highly confined optical modes. Here, we present a photoluminescence imaging
      approach for locating single QDs with respect to alignment features with an
      average position uncertainty <30 nm (<10 nm when using a solid-immersion lens),
      which represents an enabling technology for the creation of optimized single QD
      devices. To that end, we create QD single-photon sources, based on a circular
      Bragg grating geometry, that simultaneously exhibit high collection efficiency
      (48%+/-5% into a 0.4 numerical aperture lens, close to the theoretically
      predicted value of 50%), low multiphoton probability (g(2)(0) <1%), and a
      significant Purcell enhancement factor (~3).

PMID- 26211443
TI  - Canine Stifle Biomechanics Associated With Tibial Tuberosity Advancement
      Predicted Using a Computer Model.
AB  - OBJECTIVE: To evaluate the effects of tibial tuberosity advancement (TTA) on
      canine biomechanics in the cranial cruciate ligament (CrCL)-deficient stifle
      using a 3-dimensional quasi-static rigid body pelvic limb computer model
      simulating the stance phase of gait. STUDY DESIGN: Computer simulations. ANIMALS:
      A 5-year-old neutered male Golden Retriever weighing 33 kg. METHODS: A TTA was
      implemented in a previously developed canine pelvic limb computer model using the
      tibial plateau slope and common tangent planning techniques. Ligament loads,
      relative tibial translation, and relative tibial rotation were determined and
      compared to CrCL-intact and CrCL-deficient stifles. RESULTS: The TTA
      significantly decreased peak caudal cruciate ligament load, significantly
      increased peak lateral collateral ligament load, and significantly changed peak
      medial collateral ligament load occurrence, while there was no significant
      difference in peak patellar ligament load compared to the CrCL-intact stifle.
      Compared to the CrCL-deficient stifle, peak caudal cruciate, lateral collateral
      and medial collateral ligament loads significantly decreased, while peak patellar
      ligament load was similar, peak relative tibial translation significantly
      decreased and peak relative tibial rotation was converted to external rotation in
      the TTA-treated stifle. Each TTA planning technique generated similar caudal
      cruciate, medial collateral, and patellar ligament loading as well as relative
      tibial translation, but lateral collateral ligament loading and occurrence of
      relative tibial rotation differed significantly across the techniques.
      CONCLUSIONS: Model-predicted stifle ligament loads improved following TTA
      compared to the CrCL-deficient stifle, but TTA did not restore CrCL-intact stifle
      biomechanics. The TTA effectively reduced tibial translation, but tibial rotation
      was not stabilized.

PMID- 26211444
TI  - Minocycline ameliorates hypoxia-induced blood-brain barrier damage by inhibition
      of HIF-1alpha through SIRT-3/PHD-2 degradation pathway.
AB  - BACKGROUND: Minocycline, a second-generation tetracycline alleviates neuro
      inflammation and protects the blood-brain barrier (BBB) in ischemia stroke.
      However, the effect of minocycline in hypoxia-induced BBB damage is unclear.
      Here, we have investigated the effect of minocycline under hypoxia and explored
      its possible underlying mechanisms. METHODS: The effect of minocycline was
      examined in vitro in Human Brain Microvascular Endothelial Cells (HBMECs) using
      Trans Epithelial Electric Resistance (TEER). Protein and mRNA expression of
      Hypoxia-Inducible Factors-1alpha (HIF-1alpha), matrix metalloproteinases (MMP-2
      and MMP-9) and tight junction proteins (TJs) were detected by using Western blot
      and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The
      translocation and transcription of HIF-1alpha were detected by using
      immunocytochemistry and luciferase reporter assay. In vivo, to adult male Sprague
      Dawley (SD) rats under hypobaric hypoxia were administered minocycline for 1h and
      BBB permeability was tested by using Evans Blue and Transmission Electron
      Microscopy (TEM). Also, reduction of NAD-dependent deacetylase sirtuin-3 (SIRT
      3)/proline hydroxylase-2 (PHD-2) signaling pathway was evaluated. RESULTS:
      Minocycline increased TEER in HBMECs after hypoxia (P<0.05), and reduced the
      extravasation of Evans Blue (P<0.05) and colloidal gold nanoparticles in rats.
      Minocycline administration significantly reduced HIF-1alpha expression, protein
      and mRNA expression of MMP-2, MMP-9 and Vascular Endothelial Growth Factor (VEGF)
      (P<0.05), and increased TJs (ZO-1, claudin-5 and occluding) (P<0.05) in HBMECs
      after hypoxia. Furthermore, minocycline reversed the hypoxia-induced reduction of
      PHD-2 (P<0.05) and SIRT-3 (P<0.05). Effects of minocycline were abolished by
      siRNA-mediated knockdown of SIRT-3 in the brain. CONCLUSIONS: Minocycline
      inhibits HIF-1alpha-mediated cellular responses and protects BBB integrity
      through SIRT-3/PHD-2 pathway, proving to be a potential drug for the prevention
      and treatment of hypoxic brain injuries.

PMID- 26211446
TI  - 17beta-Estradiol up-regulates Nrf2 via PI3K/AKT and estrogen receptor signaling
      pathways to suppress light-induced degeneration in rat retina.
AB  - Human age-related retinal diseases, such as age-related macular degeneration
      (AMD), are intimately associated with decreased tissue oxygenation and hypoxia.
      Different antioxidants have been investigated to reverse AMD. In the present
      study, we describe the antioxidant 17beta-estradiol (betaE2) and investigate its
      protective effects on retinal neurons. Fourteen days after ovariectomy, adult
      Sprague-Dawley rats were exposed to 8000-lux light for 12h to induce retinal
      degeneration. Reactive oxygen species (ROS) levels were assessed by confocal
      fluorescence microscopy using 2,7-dichlorofluorescein diacetate. Nuclear factor
      erythroid 2-related factor 2 (Nrf2) and antioxidant enzyme mRNA expression were
      detected by real-time PCR. Western blotting was used to evaluate NRF2 activation.
      NRF2 translocation was determined by immunohistochemistry, with morphological
      changes monitored by hematoxylin and eosin staining. Following light exposure,
      betaE2 significantly reduced ROS production. betaE2 also up-regulated NRF2 mRNA
      and protein levels, with maximal expression at 4 and 12h post-exposure,
      respectively. Interestingly, following betaE2 administration, NRF2 was
      translocated from the cytoplasm to the nucleus, primarily in the outer nuclear
      layer. betaE2 also up-regulated NRF2, which triggered phase-2 antioxidant enzyme
      expression (superoxide dismutases 1 and 2, catalase, glutaredoxins 1 and 2, and
      thioredoxins 1 and 2), reduced ROS production, and ameliorated retinal damage.
      However, the beneficial effects of betaE2 were markedly suppressed by
      pretreatment with LY294002 or ICI182780, specific inhibitors of the
      phosphatidylinositol 3-kinase-Akt (PI3K/AKT), and estrogen receptor (ER)
      signaling pathways, respectively. Taken together, these observations suggest that
      betaE2 exerts antioxidative effects following light-induced retinal degeneration
      potentially via NRF2 activation. This protective mechanism may depend on two
      pathways: a rapid, non-genomic-type PI3K/AKT response, and a genomic-type ER
      dependent response. Our data provide evidence that betaE2 is a potentially
      effective in the treatment of retinal degeneration diseases. 

PMID- 26211445
TI  - BDNF over-expression increases olfactory bulb granule cell dendritic spine
      density in vivo.
AB  - Olfactory bulb granule cells (GCs) are axon-less, inhibitory interneurons that
      regulate the activity of the excitatory output neurons, the mitral and tufted
      cells, through reciprocal dendrodendritic synapses located on GC spines. These
      contacts are established in the distal apical dendritic compartment, while GC
      basal dendrites and more proximal apical segments bear spines that receive
      glutamatergic inputs from the olfactory cortices. This synaptic connectivity is
      vital to olfactory circuit function and is remodeled during development, and in
      response to changes in sensory activity and lifelong GC neurogenesis.
      Manipulations that alter levels of the neurotrophin brain-derived neurotrophic
      factor (BDNF) in vivo have significant effects on dendritic spine morphology,
      maintenance and activity-dependent plasticity for a variety of CNS neurons, yet
      little is known regarding BDNF effects on bulb GC spine maturation or
      maintenance. Here we show that, in vivo, sustained bulbar over-expression of BDNF
      in transgenic mice produces a marked increase in GC spine density that includes
      an increase in mature spines on their apical dendrites. Morphometric analysis
      demonstrated that changes in spine density were most notable in the distal and
      proximal apical domains, indicating that multiple excitatory inputs are
      potentially modified by BDNF. Our results indicate that increased levels of
      endogenous BDNF can promote the maturation and/or maintenance of dendritic spines
      on GCs, suggesting a role for this factor in modulating GC functional
      connectivity within adult olfactory circuitry. 

PMID- 26211448
TI  - Regioswitchable Palladium-Catalyzed Decarboxylative Coupling of 1,3-Dicarbonyl
      Compounds.
AB  - A palladium-catalyzed chemo- and regioselective coupling of 1,3-dicarbonyl
      compounds via an allylic linker has been developed. This reaction, which displays
      broad substrate scope, forms two C-C bonds and installs two all-carbon quaternary
      centers. The regioselectivity of the reaction can be predictably controlled by
      utilizing an enol carbonate of one of the coupling partners. 

PMID- 26211449
TI  - The Cancer Stories Project: narratives of encounters with cancer in Aotearoa, New
      Zealand.
AB  - OBJECTIVE: The Cancer Stories Study aimed to identify the factors that empower
      people who have experienced cancer. More specifically the project sought to
      explore the coping and support mechanisms people adopted to help understand and
      manage their cancer experience. METHODS: A participatory research approach
      involved researchers and consumers working in partnership on the project. This
      research team agreed on a qualitative method that focused on cancer survivors'
      personal stories. Semi-structured interviews were conducted with 38 cancer
      survivors in the lower half of the North Island, New Zealand (NZ). Generic
      qualitative analysis methods were employed including the recording, transcribing
      and thematic coding of interview narratives. RESULTS: Seven distinct themes were
      classified under the overarching theme of empowerment: attitude, change,
      family/whanau and friends, healthcare professionals and services, sources of
      support, employment and tangata whenua (NZ's indigenous peoples). The unique
      needs of each individual were strongly emphasised throughout all the themes
      indicating a 'one-size-fits-all' approach has its limitations. The need for
      improvements in communication, cultural and spiritual care was highlighted by
      many participants. CONCLUSIONS: It is anticipated that this project will
      contribute to a greater understanding of the factors that might empower people in
      their cancer journey. An empowerment lens, that asks how those affected by cancer
      may be further enabled at an individual, family/whanau, employer and healthcare
      professional level may be useful in assisting people navigate and manage their
      cancer.

PMID- 26211447
TI  - Schizophrenia: Evidence implicating hippocampal GluN2B protein and REST
      epigenetics in psychosis pathophysiology.
AB  - The hippocampus is strongly implicated in the psychotic symptoms of
      schizophrenia. Functionally, basal hippocampal activity (perfusion) is elevated
      in schizophrenic psychosis, as measured with positron emission tomography (PET)
      and with magnetic resonance (MR) perfusion techniques, while hippocampal
      activation to memory tasks is reduced. Subfield-specific hippocampal molecular
      pathology exists in human psychosis tissue which could underlie this neuronal
      hyperactivity, including increased GluN2B-containing NMDA receptors in
      hippocampal CA3, along with increased postsynaptic density protein-95 (PSD-95)
      along with augmented dendritic spines on the pyramidal neuron apical dendrites.
      We interpret these observations to implicate a reduction in the influence of a
      ubiquitous gene repressor, repressor element-1 silencing transcription factor
      (REST) in psychosis; REST is involved in the age-related maturation of the NMDA
      receptor from GluN2B- to GluN2A-containing NMDA receptors through epigenetic
      remodeling. These CA3 changes in psychosis leave the hippocampus liable to
      pathological increases in neuronal activity, feedforward excitation and false
      memory formation, sometimes with psychotic content. 

PMID- 26211450
TI  - Surface-Assisted Cyclodehydrogenation; Break the Symmetry, Enhance the
      Selectivity.
AB  - Selectivity in chemical reactions is a major objective in industrial processes to
      minimize spurious byproducts and to save scarce resources. In homogeneous
      catalysis the most important factor which determines selectivity is structural
      symmetry. However, a transfer of the symmetry concept to heterogeneous catalysis
      still requires a detailed comprehension of the underlying processes. Here, we
      investigate a ring-closing reaction in surface-confined meso-substituted
      porphyrin molecules by scanning tunneling microscopy, temperature-programmed
      desorption, and computational modeling. The identification of reaction
      intermediates enables us to analyze the reaction pathway and to conclude that the
      symmetry of the porphyrin core is of pivotal importance regarding product yields.

PMID- 26211451
TI  - Interpreting the modern distribution of Myrtaceae using a dated molecular
      phylogeny.
AB  - The angiosperm family Myrtaceae has extant and fossil taxa from all southern
      continents and is assumed to be of Gondwanan origin. Many modern groups contain
      sister taxa that have disjunct transoceanic distributions, which can be
      interpreted as a result of either vicariance or long-distance dispersal and
      establishment (LDDE). Further, some Myrtaceae groups occur on Pacific islands
      with enigmatic geological histories. We tested hypotheses of vicariance and LDDE
      by estimating divergence times using a relaxed molecular clock calibrated with 12
      fossils. In total, 88 genera and 202 species were sampled, representing both
      subfamilies and all tribes of Myrtaceae. We reconstructed the family as Gondwanan
      in origin. Of the 22 geographically disjunct sister groups in our study, up to
      six are potentially explained as the product of vicariance, three resulting from
      overland dispersal via new land connections, and 13 due to LDDE events. Nine of
      the 13 hypothesized LDDE events occurred in fleshy-fruited taxa. Our results
      indicate that most of the transoceanic distribution patterns in Myrtaceae have
      occurred since the Miocene due to LDDE, whereas inferred vicariance events all
      occurred before the Late Eocene. There are many instances of sister relationships
      between species-poor and species-rich groups in Myrtaceae, and at least three
      occurrences of geographically isolated taxa on long branches of the phylogeny
      (Arillastrum, Myrtus, and Tepualia), whose modern-day distributions are difficult
      to explain without additional fossil or geological evidence. 

PMID- 26211452
TI  - How synthetic membrane systems contribute to the understanding of lipid-driven
      endocytosis.
AB  - Synthetic membrane systems, such as giant unilamellar vesicles and solid
      supported lipid bilayers, have widened our understanding of biological processes
      occurring at or through membranes. Artificial systems are particularly suited to
      study the inherent properties of membranes with regard to their components and
      characteristics. This review critically reflects the emerging molecular mechanism
      of lipid-driven endocytosis and the impact of model membrane systems in
      elucidating the complex interplay of biomolecules within this process. Lipid
      receptor clustering induced by binding of several toxins, viruses and bacteria to
      the plasma membrane leads to local membrane bending and formation of tubular
      membrane invaginations. Here, lipid shape, and protein structure and valency are
      the essential parameters in membrane deformation. Combining observations of
      complex cellular processes and their reconstitution on minimal systems seems to
      be a promising future approach to resolve basic underlying mechanisms. This
      article is part of a Special Issue entitled: Mechanobiology. 

PMID- 26211453
TI  - Mechanotransduction in neutrophil activation and deactivation.
AB  - Mechanotransduction refers to the processes through which cells sense mechanical
      stimuli by converting them to biochemical signals and, thus, eliciting specific
      cellular responses. Cells sense mechanical stimuli from their 3D environment,
      including the extracellular matrix, neighboring cells and other mechanical
      forces. Incidentally, the emerging concept of mechanical homeostasis,long term or
      chronic regulation of mechanical properties, seems to apply to neutrophils in a
      peculiar manner, owing to neutrophils' ability to dynamically switch between the
      activated/primed and deactivated/deprimed states. While neutrophil activation has
      been known for over a century, its deactivation is a relatively recent discovery.
      Even more intriguing is the reversibility of neutrophil activation and
      deactivation. We review and critically evaluate recent findings that suggest
      physiological roles for neutrophil activation and deactivation and discuss
      possible mechanisms by which mechanical stimuli can drive the oscillation of
      neutrophils between the activated and resting states. We highlight several
      molecules that have been identified in neutrophil mechanotransduction, including
      cell adhesion and transmembrane receptors, cytoskeletal and ion channel
      molecules. The physiological and pathophysiological implications of such
      mechanically induced signal transduction in neutrophils are highlighted as a
      basis for future work. This article is part of a Special Issue entitled:
      Mechanobiology. 

PMID- 26211454
TI  - Granulomatous reaction to red tattoo pigment treated with allopurinol.
AB  - Granulomatous reactions to tattoo ink are most commonly associated with mercury
      sulfide, a component of red pigments. Treatment options show limited results.
      Allopurinol, an inhibitor of xanthine oxidase, has been reported as a successful
      alternative treatment to granulomatous disorders, such as sarcoidosis and
      granulomatous reactions to fillers and tattoos. We report a case of granulomatous
      reaction to red tattoo pigment treated with allopurinol for 6 months. Good
      clinical improvement could be noticed during this time. Two months after we
      stopped the treatment, the lesion recurred. Allopurinol emerges as an important
      drug for the management of granulomatous reactions caused by tattoo pigments.
      Based on the significant clinical improvement noticed during its use, we
      recommend new studies to elucidate all the potential benefits of the use of
      allopurinol for the treatment of granulomatous reactions to tattoo ink. 

PMID- 26211455
TI  - The Japanese version of the Rapid Dementia Screening Test is effective compared
      to the clock-drawing test for detecting patients with mild Alzheimer's disease.
AB  - BACKGROUND: The Japanese version of the Rapid Dementia Screening Test (RDST-J)
      and the clock-drawing test (CDT) are both brief psychometric screening tools used
      to detect the severity of Alzheimer's disease. It remains unclear, however, which
      is more effective when screening for mild Alzheimer's disease. METHODS: We
      administered the RDST-J and CDT to 250 patients with very mild to severe
      Alzheimer's disease and to 49 healthy volunteers. Patients with a Mini-Mental
      State Examination score of 12-26 had Clinical Dementia Rating (CDR) scores from
      0.5 to 3. Patients were divided into four groups according to CDR score. We
      performed one-way factorial anova between the four groups and control subjects
      based on the CDT and RDST-J scores. RESULTS: Data analysis revealed that RDST-J
      could distinguish patients with CDR 0.5 from the controls, but CDT could not.
      Furthermore, the sensitivity of a RDST-J score >=8 was 57.1%, with a specificity
      of 81.0%, and the sensitivity of a RDST-J score >=9 was 79.6%, with a specificity
      of 55.1% for discriminating CDR 0.5 from controls. CONCLUSIONS: RDST-J is a more
      effective tool than CDT for distinguishing CDR 0.5 from controls.

PMID- 26211456
TI  - Evaluation of bone mass in children and young adults with juvenile idiopathic
      arthritis.
AB  - OBJECTIVES: To examine bone mineral density (BMD) in the spines of patients with
      juvenile idiopathic arthritis (JIA), and to identify the main predictors of spine
      BMD. METHODS: 160 patients with JIA (82 female, 78 male; median age, 8.7+/-3.9
      years (range, 2.2-18.2 years)) who fulfilled the International League of
      Associations for Rheumatology (ILAR) criteria were enrolled. All subjects
      underwent an initial dual energy x-ray absorptiometry (DXA) scan of the lumbar
      spine, while 114 and 87 patients underwent a second and third scan, respectively.
      The data were compared with those obtained for 114 sex- and age-matched healthy
      controls. RESULTS: The DXA scans revealed that the JIA patients had a significant
      spine BMD deficit compared with control subjects (p<0.001). Longitudinal
      comparison of patients revealed no significant short-term improvement in the
      spine BMD. Spine BMD correlated with the age (p<0.05), subtype (p<0.05), and
      disease activity (p<0.01), BMI (p=0.001), glucocorticoid (GC) exposure (p< 0.05),
      methotrexate (MTX) therapy (p<0.05), and non-steroidal anti-inflammatory agents
      (NSAIDs) (p<0.05), erythrocyte sedimentation rate (ESR) (p<0.01), and C-reactive
      protein (CRP) levels (p<0.01). CONCLUSIONS: Patients with JIA have low bone mass,
      especially those in the polyarticular group >7 years old with higher disease
      activity.

PMID- 26211457
TI  - N(6) -Methyladenine: A Potential Epigenetic Mark in Eukaryotic Genomes.
AB  - N(6) -methyladenine (6mA) is known to be an epigenetic mark in bacterial genomes.
      Three studies have now demonstrated the existence of significant levels of 6mA in
      the genomes of several phylogenetically distinct eukaryotes, along with findings
      that suggest that 6mA may act as a dynamic epigenetic mark in the regulation of
      eukaryotic gene expression. 

PMID- 26211458
TI  - Determination of fast electrode kinetics facilitated by use of an internal
      reference.
AB  - The concept of using an internal reversible reference process as a calibration in
      the determination of fast electrode kinetics has been developed and applied with
      the technique of Fourier transformed large amplitude ac voltammetry to minimize
      the influence of errors arising from uncertainties in parameters such as
      electrode area (A), concentration (C), diffusion coefficient (D), and
      uncompensated resistance (Ru). Since kinetic parameters (electron transfer rate
      constant, k(0), and electron transfer coefficient, alpha) are irrelevant in the
      voltammetric characterization of a reversible reaction, parameters such as A, C,
      D, and Ru can be calibrated using the reversible process prior to quantification
      of the electrode kinetics associated with the fast quasi-reversible process. If
      required, new values of parameters derived from the calibration exercise can be
      used for the final determination of k(0) and alpha associated with the process of
      interest through theory-experimental comparison exercises. Reference to the
      reversible process is of greatest significance in diminishing the potentially
      large impact of systematic errors on the measurement of electrode kinetics near
      the reversible limit. Application of this method is demonstrated with respect to
      the oxidation of tetrathiafulvalene (TTF), where the TTF(0/*+) process is used as
      a reversible internal reference for the measurement of the quasi-reversible
      kinetics of the TTF(*+/2+) process. The more generalized concept is demonstrated
      by use of the Fc(0/+) (Fc = ferrocene) reversible process as an internal
      reference for measurement of the kinetics of the Cc(+/0) (Cc(+) = cobaltocenium)
      process. Via the internal reversible reference approach, a k(0) value of 0.55 cm
      s(-1) was obtained for the TTF(*+/2+) process at a glassy carbon electrode and
      2.7 cm s(-1) for the Cc(+/0) one at a carbon fiber microelectrode in acetonitrile
      (0.1 M Bu4NPF6). 

PMID- 26211459
TI  - A-ring substituted 17beta-arylsulfonamides of 17beta-aminoestra-1,3,5(10)-trien-3
      ol as highly potent reversible inhibitors of steroid sulfatase.
AB  - Steroid sulfatase (STS) catalyzes the hydrolysis of the sulfate ester group in
      biologically inactive sulfated steroids to give biologically active steroids.
      Inhibitors of STS are considered to be potential therapeutics for treating
      hormone-dependent cancers such as ER(+) breast cancer. A series of 4-substituted
      17beta-arylsulfonamides of 17beta-aminoestra-1,3,5(10)-trien-3-ol were prepared
      and examined as STS inhibitors. The presence of a NO2 or Br at the 2-position of
      the A-ring resulted in a decrease in potency compared to their A-ring
      unsubstituted counterparts. However the presence of a nitro group or fluorine
      atom at the 4-position of the A-ring resulted in an increase in potency and one
      of these compounds exhibited a Ki(app) value of 1 nM. Modeling studies provided
      insight into how these compounds interact with active site residues. The anti
      proliferative activity of the 3'-Br, 3'-CF3, 4-NO2-3'-Br and 4-NO2-3'-CF3
      derivatives were examined using the NCI 60-cell-line panel and found to have mean
      graph midpoint values of 1.9-3.4 MUM.

PMID- 26211460
TI  - Antiproliferative and apoptosis-inducing activities of novel naphthalimide-cyclam
      conjugates through dual topoisomerase (topo) I/II inhibition.
AB  - A novel series of naphthalimide-cyclam conjugates were designed and synthesized.
      Among them, compounds 4c, 4d, 8c and 8d which bearing long lipophilic alkyl
      chains, displayed comparable or more potent cytotoxic activities against human
      tumor cell lines than amonafide. Furthermore, the four compounds were proved to
      possess strong inhibition against both topoisomerase I and II. The representative
      compound 8c exhibited moderate DNA intercalation activity. Molecular modeling
      studies identified the possible interaction of compound 8c with the molecular
      target by forming topoisomerase/DNA/drug ternary complex. Finally, derivatives
      with long lipophilic alkyl chains could efficiently induce apoptosis. 

PMID- 26211461
TI  - Chemoenzymatic synthesis and cytotoxicity of oenanthotoxin and analogues.
AB  - We developed a synthetic scheme for the synthesis of naturally occurring (14R)
      oenanthotoxin and several analogs. Key-steps of this synthesis were an efficient
      homo-coupling of alkynes and a chemoenzymatic resolution of racemic oenanthotoxin
      using novozyme 435 and vinyl acetate. The compounds were screened for their
      cytotoxic activity using a photometric sulforhodamine B assays and several human
      tumor cell lines. Oenanthotoxin and many derivatives thereof were cytotoxic to
      tumor cell lines as well as to non-malignant mouse fibroblasts. The highest
      activity was determined for human ovarian cancer cells A2780 with EC50 = 3.8 MUM.

PMID- 26211462
TI  - Design, synthesis and biological evaluation of isoquinoline-based derivatives as
      novel histone deacetylase inhibitors.
AB  - The design, synthesis and biological evaluation of a series of isoquinoline-based
      hydroxamic acid compounds as novel HDACs inhibitors were reported herein. A
      detailed SAR study showed most of the compounds displayed good to excellent
      inhibitory activities against HDAC1, 3, 6. The IC50 values of compound 10 c
      against HDAC1, 3, 6 were 4.17 +/- 0.11 nM, 4.00 +/- 0.10 nM, 3.77 +/- 0.07 nM,
      respectively. Most of the compounds showed great anti-proliferative activities
      against RPMI 8226, HCT 116 and Hep G2 cells. The IC50 values of compounds 10 a-h
      against RPMI 8226 cancer cell proliferation were all below 1 MUM. HCT 116 cell
      was sensitive to the compounds 10 a, 10 f-g and 18 a with the IC50 values <0.3
      MUM. The active compounds 10a-d did not show inhibitory activity against hERG
      channel. All these evidence indicated these compounds had great potential as
      HDACs inhibitors for the further development.

PMID- 26211464
TI  - Response to Comment on "Is There a Correlation Between Androgens and Sexual
      Desire in Women?".

PMID- 26211465
TI  - Percentage of positive prostate biopsies independently predicts biochemical
      outcome following radiation therapy for prostate cancer.
AB  - BACKGROUND: This work aims to definitely show the ability of percentage of
      positive biopsy cores (%PC) to independently predict biochemical outcome beyond
      traditional pretreatment risk-factors in prostate cancer (PCa) patients treated
      with radiotherapy. METHODS: A cohort of 2493 men belonging to the EUREKA-2
      retrospective multicentric database on (PCa) and treated with external-beam
      radiation therapy (EBRT) as primary treatment comprised the study population
      (median follow-up 50 months). A Cox regression time to prostate-specific antigen
      (PSA) failure analysis was performed to evaluate the predictive power of %PC,
      both in univariate and multivariate settings, with age, pretreatment PSA,
      clinical-radiological staging, bioptic Gleason Score (bGS), RT dose and RT +/-
      ADT as covariates. RESULTS: P statistics for %PC is lower than 0.001 both in
      univariate and multivariate models. %PC as a continuous variable yields an AUC of
      69% in ROC curve analysis for biochemical relapse. Four classes of %PC (1-20%, 21
      50%, 51-80% and 81-100%) distinctly split patients for risk of biochemical
      relapse (overall log-rank test P<0.0001), with biochemical progression free
      survival (bPFS) at 5-years ranging from 88% to 58% and 10-years bPFS ranging from
      80% to 38%. CONCLUSIONS: We strongly affirm the usefulness of %PC information
      beyond main risk factors (PSA, staging and bGS) in predicting biochemical
      recurrence after EBRT for PCa. The stratification of patients according to %PC
      may be valuable to further discriminate cases with favourable or adverse
      prognosis.

PMID- 26211466
TI  - Implementation of latent tuberculosis screening in HIV care centres: evaluation
      in a low tuberculosis incidence setting.
AB  - The screening and treatment of latent tuberculosis infection (LTBI) to prevent
      active tuberculosis (TB) is recommended by the WHO in all HIV-infected patients.
      The aim of this study was to evaluate its implementation within Belgium's HIV
      care. A multiple-choice questionnaire was sent to 55 physicians working in the
      country's AIDS reference centres. Response rate reached 62%. Only 20% screened
      all their HIV-infected patients for LTBI. Screening methods used and their
      interpretation vary from one physician to another. The main barriers to the
      implementation of LTBI screening and treatment, as perceived by the participants,
      are lack of sensitivity of screening tools, risks associated with polypharmacy
      and toxicity of treatment. The poor coverage of LTBI screening reported here and
      the inconsistency in methods used raises concern. However, this was not
      unexpected as, in low-TB incidence countries, who, when and how to screen for
      LTBI remains unclear and published guidelines show important disparities.
      Recently, a targeted approach in which only HIV-infected patients at highest risk
      of TB are screened has been suggested. Such a strategy would limit unnecessary
      exposure to LTBI treatment. This methodology was approved by 80% of the
      participants and could therefore achieve greater coverage. Its clinical
      validation is still pending. 

PMID- 26211463
TI  - beta-Arrestin scaffolds and signaling elements essential for the obestatin/GPR39
      system that determine the myogenic program in human myoblast cells.
AB  - Obestatin/GPR39 signaling stimulates skeletal muscle repair by inducing the
      expansion of satellite stem cells as well as myofiber hypertrophy. Here, we
      describe that the obestatin/GPR39 system acts as autocrine/paracrine factor on
      human myogenesis. Obestatin regulated multiple steps of myogenesis: myoblast
      proliferation, cell cycle exit, differentiation and recruitment to fuse and form
      multinucleated hypertrophic myotubes. Obestatin-induced mitogenic action was
      mediated by ERK1/2 and JunD activity, being orchestrated by a G-dependent
      mechanism. At a later stage of myogenesis, scaffolding proteins beta-arrestin 1
      and 2 were essential for the activation of cell cycle exit and differentiation
      through the transactivation of the epidermal growth factor receptor (EGFR). Upon
      obestatin stimulus, beta-arrestins are recruited to the membrane, where they
      functionally interact with GPR39 leading to Src activation and signalplex
      formation to EGFR transactivation by matrix metalloproteinases. This signalplex
      regulated the mitotic arrest by p21 and p57 expression and the mid- to late
      stages of differentiation through JNK/c-Jun, CAMKII, Akt and p38 pathways. This
      finding not only provides the first functional activity for beta-arrestins in
      myogenesis but also identify potential targets for therapeutic approaches by
      triggering specific signaling arms of the GPR39 signaling involved in myogenesis.

PMID- 26211472
TI  - Dose-dependent effects of neuropeptide Y on the regulation of preadipocyte
      proliferation and adipocyte lipid synthesis via the PPARgamma pathways.
AB  - The objective of this study was to investigate the impact of neuropeptide Y (NPY)
      on preadipocyte proliferation and differentiation. Preadipocytes were incubated
      with a range of concentrations of NPY (10(-15)M - 10(-7)M). After NPY-induced
      differentiation, the extent of preadipocyte adipogenesis was evaluated. The
      expressions levels of related adipocyte markers such as PPARgamma, C/EBPalpha and
      DLK-1 were examined by real-time PCR (RT-PCR) or western blot analysis.
      Furthermore, the mitogen-activated protein kinase (MAPK) signaling pathway
      proteins were also analyzed by western blot. Our results showed that low doses of
      NPY stimulated preadipocyte viability and proliferation, while high NPY doses
      inhibited cell viability. At high concentrations of NPY significantly promoted
      lipid accumulation and increased the size of lipid droplets. DLK-1 mRNA
      expression was inhibited, but the expression levels of PPARgamma and C/EBPalpha
      were increased during differentiation with the presence of high concentration of
      NPY. High-dose NPY also suppressed the phosphorylation of the extracellular
      signal-regulated kinase (ERK) 1/2 protein. We conclude that NPY has a biphasic
      effect on preadipocyte proliferation. A high dose inhibits the proliferation of
      3T3-L1 cell while promotes adipocyte differentiation, increasing lipid
      accumulation especially enlarged lipid droplets' size. NPY may lead to a better
      understanding for drug development to prevent hyperplastic obesity and
      hypertrophic obesity.

PMID- 26211473
TI  - Standardization of FT4 and harmonization of TSH measurements - a request for
      input from endocrinologists and other physicians.
AB  - Given the prevalence of thyroid disorders and the subtle signs and symptoms that
      may accompany subclinical disease, reliable laboratory testing for serum TSH and
      free thyroid hormones is important for both primary care physicians and
      endocrinologists. The laboratory community has recognized the need for
      standardization of thyroid function tests to achieve comparability of measurement
      results between methods. This applies in particular to tests for free T4 (FT4),
      which may be considered controversial in terms of clinical and analytical
      validity. However, variability is also observed with TSH testing - a fact which
      has not been emphasized in ongoing discussions regarding lowering the upper limit
      of normal and/or common decision limits to start treatment for hypothyroidism. In
      response to this need, the International Federation of Clinical Chemistry and
      Laboratory Medicine (IFCC) Committee for Standardization of Thyroid Function
      Tests worked over the years towards the goal of standardization of FT4 and TSH
      testing. 

PMID- 26211474
TI  - Combination therapy for the treatment of Crohn's disease.
AB  - INTRODUCTION: Crohn's disease (CD) is an idiopathic inflammatory disorder of the
      gastrointestinal tract traditionally treated by the step-wise use of
      corticosteroids, antimetabolites and TNF-alpha antagonists. However, recent
      evidence indicates that the early introduction of drug combinations might be a
      superior strategy to step-care. AREAS COVERED: In this article, we review
      existing literature regarding the efficacy and safety of combination drug therapy
      for the management of CD. Five major databases: MEDLINE, EMBASE, PubMed, the
      Cochrane Library (CENTRAL) and DDW abstracts were electronically searched from
      inception to February 2015 for any relevant studies. EXPERT OPINION: Existing
      data strongly support the use of combination therapy for CD. The benefit of this
      approach appears to outweigh any associated risks. Until the role of gut
      selective therapies are better established, combination therapy should be
      considered the standard treatment approach for CD.

PMID- 26211477
TI  - Correction: Chemopreventive activity of ellagitannins and their derivatives from
      black raspberry seeds on HT-29 colon cancer cells.
AB  - Correction for 'Chemopreventive activity of ellagitannins and their derivatives
      from black raspberry seeds on HT-29 colon cancer cells' by Hyunnho Cho et al.,
      Food Funct., 2015, 6, 1675-1683. 

PMID- 26211476
TI  - Recombinant disintegrin domain of human ADAM9 inhibits migration and invasion of
      DU145 prostate tumor cells.
AB  - One of the most important features of malignant cells is their capacity to invade
      adjacent tissues and metastasize to distant organs. This process involves the
      creation, by tumor and stroma cells, of a specific microenvironment, suitable for
      proliferation, migration and invasion of tumor cells. The ADAM family of proteins
      has been involved in these processes. This work aimed to investigate the role of
      the recombinant disintegrin domain of the human ADAM9 (rADAM9D) on the adhesive
      and mobility properties of DU145 prostate tumor cells. rADAM9D was able to
      support DU145 cell adhesion, inhibit the migration of DU145 cells, as well as the
      invasion of this cell line through matrigel in vitro. Overall this work
      demonstrates that rADAM9D induces specific cellular migratory properties when
      compared with different constructs having additional domains, specially those of
      metalloproteinase and cysteine-rich domains. Furthermore, we showed that rADAM9D
      was able to inhibit cell adhesion, migration and invasion mainly through
      interacting with alpha6beta1 in DU145 tumor cell line. These results may
      contribute to the development of new therapeutic strategies for prostate cancer. 

PMID- 26211478
TI  - Less is More--Optimization of DNA Extraction from Canine Feces.
AB  - Although most DNA crime laboratories may not encounter fecal samples often, they
      are a familiar sample type in non-human forensic laboratories due to their
      prevalence in the environment. Fecal matter can be challenging due to low numbers
      of nucleated cells and the presence of inhibitors that impede amplification
      success. Sampling location (internal vs. external), sampling quantity (10-200
      mg), and various extraction protocols (silica matrix, bead beating, and clean-up
      column) were evaluated to maximize DNA yield. The greatest yield of intact DNA
      was obtained using a modified silica matrix extraction protocol (VGL-Fecal) on 30
      50 mg of fecal matter collected from the external surface of a stool that had
      been dried for 24 h. This optimized sampling and extraction protocol was applied
      to a pilot study where DNA yield and genotyping success were evaluated. By
      optimizing our collection, sampling, and extraction procedures, a reliable method
      for maximizing the yield of canine fecal DNA was developed.

PMID- 26211479
TI  - Editorial Comment to MicroRNA-205 inhibits cancer cell migration and invasion via
      modulation of centromere protein F regulating pathways in prostate cancer.

PMID- 26211480
TI  - Recent progress in protein profiling of clinical tissues for next-generation
      molecular diagnostics.
AB  - Differences in protein levels and the activation of signaling pathways have been
      extensively studied in tumor tissues, but the implementation of protein profiling
      methods in routine hospital workflows lags far behind that of nucleic acid-based
      approaches. In this review, major technologies that are currently used for
      measuring protein abundances in human tissues are highlighted, and for each
      method several examples are provided. We differentiate between extract-based and
      section-based methods that are each further divided into targeted- and discovery
      based approaches (i.e., when the proteins to be analyzed are known or for finding
      promising new biomarker candidates, respectively). Current problems in protein
      profiling are addressed and ways in which protein profiling can successfully be
      implemented in routine clinical workflows are shown. 

PMID- 26211481
TI  - Exact Sciences' experience with the FDA and CMS parallel review program.
AB  - Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the
      second leading cause of cancer death among men and women combined in the USA.
      Although the benefits of early CRC detection are widely recognized, screening
      rates are suboptimal. Cologuard is a multitarget stool DNA screening test that
      offers a unique non-invasive option for CRC screening. Cologuard was the first
      product to be reviewed under a pilot parallel review program jointly conducted by
      the US FDA and the Centers for Medicare & Medicaid Services (CMS). This parallel
      review process shortened the overall review for Cologuard and resulted in a
      preliminary National Coverage Determination that coincided with FDA approval.

PMID- 26211483
TI  - The Development and Validation of a Nomogram for Identification of Potential
      Donation After Cardiac Death Donors.

PMID- 26211482
TI  - Effect of subconjunctival glucose on retinal ganglion cell survival in
      experimental retinal ischaemia and contrast sensitivity in human glaucoma.
AB  - PURPOSE: This study aims to evaluate the effect of subconjunctival glucose on the
      retinal ganglion cells (RGCs) in experimental retinal ischaemia and contrast
      sensitivity in humans with primary open-angle glaucoma (POAG). METHODS: First, we
      measured the intravitreal concentration of glucose at various time points after a
      subconjunctival injection of 100 MUl of 50% glucose to Sprague-Dawley rats. Next,
      treatment and control groups received 50% subconjunctival glucose and iso-osmotic
      (8%) saline, respectively, 1 h prior to a unilateral ischaemic retinal injury; 7
      days later, the damage profiles were compared using RGC and axon counts.
      Subsequently, we conducted a double-blind, crossover, pilot clinical study in
      seven eyes of five pseudophakic subjects with severe POAG. Subjects received
      either 0.3 mL of 50% glucose subconjunctivally or iso-osmotic (8%) saline, then
      vice versa after a 2-3 week 'wash-out' period; change in contrast sensitivity
      from baseline was the primary outcome. RESULTS: Subconjunctival glucose preserved
      approximately 60% of Brn3a-positive RGCs in all retinal zones compared with an
      80% loss in control retinas, and rescued approximately 40% of the axonal loss. In
      the human trial, the contrast sensitivity at 12 cycles/degree was 0.24 log units
      greater than baseline (95% confidence interval 0.12-0.36; P < 0.001).
      CONCLUSIONS: Subconjunctival glucose partially protects RGC somata and axons
      against an ischaemic insult and temporarily recovers contrast sensitivity in
      patients with severe POAG. Although an unlikely therapeutic strategy for POAG,
      the findings motivate further bioenergetic-based research in glaucoma and other
      optic nerve and retinal diseases, where energy failure may be part of the
      pathogenesis.

PMID- 26211484
TI  - Geriatric consultation can aid in complex treatment decisions for elderly cancer
      patients.
AB  - Treatment decisions for elderly cancer patients can be challenging. A geriatric
      assessment may identify unknown medical conditions, give insight on patients'
      ability to tolerate treatment and guide treatment decisions. Our aim was to study
      the value of a geriatric consultation in oncological decision-making. Data on
      cancer patients referred for geriatric consultation for clinical optimisation or
      due to uncertainty regarding their optimal treatment strategy were prospectively
      analysed. Outcome of geriatric evaluations, non-oncological interventions and
      suggested adaptations of oncological treatment proposals were evaluated. Seventy
      two patients were referred for consultation, over half of which in a curative
      treatment setting. Prevalence of geriatric syndromes was 93%, previously
      undiagnosed conditions were identified in 49% of patients and non-oncological
      interventions were initiated in 56%. Time was spent discussing patients'
      priorities (53% of consultations), expectations on treatment (50%) and advance
      care planning (14%). For 82% of patients, suggestions were made regarding the
      optimal treatment decision: a more intensive treatment was recommended in 39%, a
      less intensive therapy for 42% and in 19% only supportive care was suggested. The
      results demonstrate that a geriatric consultation can aid in complex treatment
      decisions and may allow for a reduction in over- and undertreatment of elderly
      cancer patients. 

PMID- 26211485
TI  - Risk-Minimizing Belief: Its Association with Smoking and Risk of Harm From
      Smoking in Northern Thailand.
AB  - Risk-minimizing beliefs refer to the underestimation of the health risks of
      particular behaviors. The aim of the study was to investigate the associations
      between risk-minimizing belief with smoking and the risk of harms from smoking in
      Northern Thailand (N=3,865). Adjusting for potential confounders, risk-minimizing
      belief was inversely associated with lifelong abstinence, positively associated
      with increased risk of being a current smoker, and weakly associated with
      increased risk of harm from smoking. Targeting risk-minimizing beliefs in current
      smokers and those who have never smoked may be useful in the Northern Thai
      population. 

PMID- 26211487
TI  - Carers and families: life and suffering among Bangladeshi psychiatric patients
      and their families in London - an interview study 3.
AB  - This paper looks at the role of Bangladeshi families in the provision of care and
      help seeking: the burden on family members but also their presumed role in the
      causation of illness. It deploys data deriving from an interview study examining
      understandings and health-related practices among British Bangladeshis with
      mental and physical illness and their carers. While families generally support
      the mentally ill, the emotional and physical burden on them can be extensive.
      Conflicts between individuals may result in accusations of sorcery, especially
      when envy is suspected. Regular travel between desh and bidesh attempts to
      maintain family unity and continues traditional understandings of serious
      sickness and disability. 

PMID- 26211486
TI  - beta-Blockers have differential effects on the murine asthma phenotype.
AB  - BACKGROUND AND PURPOSE: Our previous studies have shown the beta2 -adrenoceptor
      and its endogenous ligand, adrenaline, are required for development of the asthma
      phenotype in murine asthma models. Chronic administration of some, but not other,
      beta-blockers attenuated the asthma phenotype and led us to hypothesize that
      biased signalling was the basis of their differential effects, experimentally and
      clinically. EXPERIMENTAL APPROACH: We used mice with no detectable systemic
      adrenaline (PNMT(-/-) ) and wild-type (WT) mice to study the effects of four beta
      blockers, alprenolol, carvedilol, propranolol and nadolol, in an ovalbumin
      sensitization and challenge (Ova S/C) murine model of asthma. The parameters
      measured were inflammatory cell infiltration, mucous metaplasia and airway
      hyperresponsiveness. To interpret the pharmacological action of these ligands
      quantitatively, we conducted computer simulations of three-state models of
      receptor activation. KEY RESULTS: Ova S/C PNMT(-/-) mice do not develop an asthma
      phenotype. Here, we showed that administration of alprenolol, carvedilol or
      propranolol in the absence of interference from adrenaline using Ova S/C PNMT(-/
      ) mice resulted in the development of an asthma phenotype, whereas nadolol had no
      effect. Ova S/C WT mice did develop an asthma phenotype, and administration of
      alprenolol, propranolol and carvedilol had no effect on the asthma phenotype.
      However, nadolol prevented development of the asthma phenotype in Ova S/C WT
      mice. Computer simulations of these four ligands were consistent with the
      isolated three-state receptor model. CONCLUSION AND IMPLICATIONS: beta-Blockers
      have different effects on the murine asthma phenotype that correlate with
      reported differences in activation or inhibition of downstream beta2 
      adrenoceptor signalling pathways.

PMID- 26211488
TI  - Pediatric myringoplasty: Prognostic factors in surgical outcome and hearing
      threshold recovery.
AB  - CONCLUSIONS: This study shows as decisive factors the history of tympanostomy
      tube insertion and surgical approach. The closure of the perforation observed at
      the 6th post-operative month is almost definitive, without finding significant
      differences ahead. The myringoplasty can be performed simultaneously in bilateral
      perforations and in a day-case basis with same success rates. Astatistically
      significant audiometric improvement area is described, after myringoplasty,
      undescribed previously in literature. OBJECTIVES: The aim of this study was to
      evaluate prognostic factors in surgical outcome and hearing threshold after
      myringoplasty, in pediatric age. METHODS: A 10-year retrospective review of 142
      myringoplasties performed by a single surgeon of the Pediatric ENT Department of
      12 de Octubre University Hospital. Multiple prognostic factors were investigated,
      such as those related to perforation and surgery, contralateral ear status, and
      pre- and post-operative hearing threshold. RESULTS: The overall rate of closure
      of the perforation was 74.64%. The re-perforation rate was directly proportional
      to the number of tympanostomy tube insertion (OR = 1.64). Other determining
      factors were the surgical approach, the graft position and side. There was a post
      operative significant improvement (p < 0.001) insuring that the more affected
      frequencies, low (125-500 Hz) and high frequencies (4000-8000 Hz), were the more
      improved after the procedure.

PMID- 26211489
TI  - Evaluation of the immunogenicity of the quadrivalent HPV vaccine using 2 versus 3
      doses at month 21: An epidemiological surveillance mechanism for alternate
      vaccination schemes.
AB  - The cost of HPV vaccines and the need for 3 doses remains a barrier for their
      inclusion in routine vaccination schedules for girls in low and middle income
      countries. In a non-inferiority study, we aimed to compare the immunogenicity of
      a standard 3 doses and a 2 doses schedule. We enrolled 450 participants in an
      open-label non-randomized clinical trial to evaluate the immunogenicity induced
      at different ages by the licensed HPV6/11/16/18 quadrivalent vaccine in a 2 doses
      schedule (0-6 months, n = 150 girls aged 9-10 y) and 3 doses schedule (0, 2, and
      6 months; n = 150 girls aged 9-10 y and n=150 women aged 18 to 24 years). To
      assess the antibody response, blood samples were obtained at Month 7 and 21 after
      the first vaccination from participants in all study groups. cLIA testing was
      performed at Merck Research Laboratories. Antibody levels were expressed as milli
      Merck units (mMU) per ml. Primary outcome was non-inferiority (95% CI, lower
      bound >0.5) of the geometric mean titers (GMT) ratios for HPV6, HPV11, HPV16 and
      HPV18 antibodies 7 and 21 months after the first dose among girls receiving 2
      doses compared with young women and girls receiving 3 doses. All vaccinees were
      seropositive for both HPV16 and HPV18 antibodies at month 7. At month 21, 98.5
      and 56.6% of women 18-24 y old were seropositive for HPV16 and 18, respectively.
      For girls in the three doses group, seropositivity rates were 99.3 and 86.3% for
      HPV16 and 18, respectively. For girls in the two doses group rates were 99.3 and
      70.2% for HPV16 and 18, respectively. The two doses schedule was non-inferior
      compared to the 3 doses schedule in same-age girls and to the group of adult
      women after 21 months of the first vaccine dose. Our results are in agreement
      with similar trials evaluating the immune response of a 2 doses schedule of both
      HPV vaccines, supporting the recent WHO recommendation as well as the Mexican
      policy to incorporate the 2 doses schedule for girls aged 9-11 y. 

PMID- 26211494
TI  - Combinations of potent topical steroids, mercury and hydroquinone are common in
      internationally manufactured skin-lightening products: a spectroscopic study.
AB  - BACKGROUND: The topical steroids betamethasone (BM) and clobetasol propionate
      (CP) are illegal in cosmetics. Hydroquinone (HQ) and mercury (Hg) are either
      illegal or allowed only in limited concentrations (2% and 1 ppm, respectively).
      AIM: To investigate active ingredients and countries of origin of popular skin
      lightening products available in Cape Town, South Africa. METHODS: In total, 29
      products were examined; of these, 22 products were purchased from informal
      vendors, and 2 products (out of a total of 29) were purchased over the counter.
      HQ, Hg(2+) and steroids were quantified by high-performance liquid chromatography
      ultraviolet spectrophotometry, inductively coupled plasma-mass spectrometry and
      liquid chromatography-mass spectrometry, respectively. RESULTS: Of the 29
      products, 22 (75.9%), all imported and bought from informal vendors, contained
      illegal or banned ingredients: 13 (44.8%) contained steroids (9 CP, 4 BM), 12
      (41.4%) contained Hg (30-2300 ppm), and 11 (37.9%) contained HQ. Sequentially,
      the products originated from Italy (27.3%, n = 6), India (22.7%, n = 5), the
      Democratic Republic of Congo (DRC) (22.7%, n = 5), Cote d'Ivoire (9.1%, n = 2),
      USA (9.1%, n = 2), UK (4.5%, n = 1) and France (4.5%, n = 1). Two products, one
      from India and one from the DRC, contained all four ingredients (HQ, Hg, BM, CP).
      Of the 12 products containing Hg, 10 also contained HQ and/or a steroid, yet none
      listed Hg as an ingredient. A significant proportion of the steroid-containing
      products (76.9%) also contained at least one other skin-lightening agent. Not all
      internationally available products were tested, which is a limitation of the
      study. CONCLUSION: In spite of a European Union ban on skin lighteners, a third
      of the products tested were from Europe. Combinations of Hg and ultrapotent
      steroids were prominent. International law enforcement and random testing is
      needed to encourage industry compliance and help protect consumers.

PMID- 26211495
TI  - Dexmedetomidine attenuates acute lung injury induced by lipopolysaccharide in
      mouse through inhibition of MAPK pathway.
AB  - Dexmedetomidine (Dex) is widely used for sedation in intensive care units and can
      be used as an adjunct to anesthetics. Previous studies have demonstrated that Dex
      has anti-inflammatory property. In this study, we aim to explore the potential
      therapeutic effects and mechanisms of Dex on lipopolysaccharide (LPS)-induced
      acute lung injury (ALI) in mice. To induce ALI, mice were intraperitoneally
      injected with LPS, while Dex was treated 1 h before LPS injection. The
      inflammation of lung tissues was evaluated by HE stain, and bronchoalveolar
      lavage fluid (BALF) was obtained after 6 h to measure protein concentrations. We
      also used an enzyme-linked immunosorbent assay to detect the secretion levels of
      proinflammatory cytokines in the serum. Western blotting method was adopted to
      observe changes in mitogen-activated protein kinases and downstream nuclear
      transcription factors. The results showed that pretreatment with Dex considerably
      reduced neutrophil infiltration and pulmonary edema, and significantly reduced
      protein concentrations in the BALF, as well as suppressed LPS-induced elevation
      of proinflammatory cytokines (TNF-alpha and IL-1beta) in the serum. In addition,
      we observed that the molecular mechanism of Dex-mediated anti-inflammation is
      associated with decreasing phosphorylation of MKK4, MMK3/6, ERK1/2, p38MAPK, and
      JNK, and diminishing activation of Elk-1, c-Jun, and ATF-2. Dex could attenuate
      ALI induced by LPS in mice, and this effect may be mediated through the
      inhibition of MAPK pathway. 

PMID- 26211496
TI  - Efficacy and safety of perilesional/intralesional triamcinolone injections in
      oral mucous membrane pemphigoid.

PMID- 26211497
TI  - Clinical relevance of Corynebacterium pseudodiphtheriticum in lower respiratory
      tract specimens.
AB  - BACKGROUND: Corynebacterium pseudodiphtheriticum may be present as commensal
      flora of the respiratory tract and therefore it may be difficult to assess
      clinical relevance when it is cultured from lower respiratory tract specimens.
      Our objective was to determine the clinical relevance of C. pseudodiphtheriticum
      as a lower respiratory tract pathogen and to define patients at risk of
      developing lower respiratory tract infections caused by C. pseudodiphtheriticum.
      METHODS: We retrospectively identified all lower respiratory tract cultures
      positive for C. pseudodiphtheriticum over a 10-year period and assessed clinical
      relevance by predefined criteria. RESULTS: Clinical relevance was likely or
      possible in 86% of patients. Pre-existent comorbidity was present in 86% of
      patients, mostly underlying cardiac or pulmonary disease. All isolates were
      susceptible to amoxicillin. CONCLUSION: C. pseudodiphtheriticum should be
      considered a clinically relevant pathogen when cultured from the lower
      respiratory tract in symptomatic patients.

PMID- 26211498
TI  - Correction: Pentafluoroethyl-substituted alpha-silanes: model compounds for new
      insights.

PMID- 26211499
TI  - A retrospective analysis of kidney function and risk factors by Chronic Kidney
      Disease Epidemiology Collaboration (CKD-EPI) equation in elderly Chinese
      patients.
AB  - Chronic kidney disease accounts for much of the increased mortality, especially
      in the elder population. The prevalence of this disease is expected to increase
      significantly as the society ages. Our aim was to evaluate the kidney function
      and risk factors of reduced renal function among elderly Chinese patients. This
      study retrospectively collected clinical data from a total of 1062 inpatients
      aged 65 years or over. Estimated glomerular filtration rate (eGFR) was calculated
      with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
      Renal function and risk factors were also analyzed. For all 1062 subjects, the
      mean eGFR was 71.0 +/- 24.8 mL/min/1.73 m(2), and the incidence rates of reduced
      renal function, proteinuria, hematuria and leukocyturia were 31.1%, 11.8%, 6.6%
      and 8.7%, respectively. The eGFR values were 83.4 +/- 28.4, 72.2 +/- 22.9, 67.8
      +/- 24.3 and 58.8 +/- 29.1 mL/min/1.73 m(2) in the groups of 60-69, 70-79, 80-89
      and >=90 years age group (F = 15.101, p = 0.000), respectively; while the
      incidences of reduced renal function were 12.8%, 27.0%, 37.8% and 51.7% (chi(2) =
      36.143, p = 0.000). Binary logistic regression analysis showed that hyperuricemia
      (OR = 4.62, p = 0.000), proteinuria (OR = 3.96, p = 0.000), urinary tumor (OR =
      2.92, p = 0.015), anemia (OR = 2.45, p = 0.000), stroke (OR = 1.96, p = 0.000),
      hypertension (OR = 1.83, p = 0.006), renal cyst (OR = 1.64, p = 0.018), female
      (OR = 1.54, p = 0.015), coronary artery disease (OR = 1.53, p = 0.008) and age
      (OR = 1.05, p = 0.000) were the risk factors of reduced renal function. In
      conclusion, eGFR values decreased by age, while the incidence of reduced renal
      function, proteinuria, hematuria and leukocyturia increased with age. Treatment
      and control of comorbidities may slow the decline of renal function in elderly
      patients. 

PMID- 26211500
TI  - Nephro-oncology: a link in evolution.
AB  - A multidisciplinary approach represents the best method to interact with
      patients. Neoplastic and renal diseases are closely related to each other because
      of an increased risk of cancer among individuals with end-stage renal disease and
      because of the high prevalence of renal failure in cancer patients. Physicians
      should be able to know how to prevent and treat the possible complications which
      may appear during the course of neoplastic disease that may lead to kidney damage
      such as the Acute Tumor Lysis Syndrome, disorders of hydroelectrolitic balance,
      metabolic alterations in the calcium-phosphorus, anemia, interstitial and
      glomerular impairment due to chemotherapy. It is very important to know patients'
      renal function and directly monitor it, before and during treatment, using
      formulas for estimating glomerular filtration rate (GFR) and above all, specific
      biomarkers are more early and sensitive than the increase of creatinine, like
      neutrophil gelatinase-associated lipocalin. Additionally, physician should
      consider that alteration of GFR or substitutive renal treatments severely
      influence dosage of tumor markers and it could lead to wrong diagnosis of cancer.
      The aim of this article is to provide a review of problems related to cancer
      relevant in the development of renal failure and try to define the best
      therapeutic strategies to cope with possible kidney imbalances induced by cancer
      or its treatment. 

PMID- 26211501
TI  - Vitamin D supplements in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a significant public health problem and Vitamin D
      deficiency is prevalent in CKD and might be associated with calcium and phosphate
      metabolism, cardiovascular disease, infections as well as the progress of kidney
      dysfunction. Emerging evidence implies that Vitamin D supplements may be of
      benefit to CKD. Based on existing laboratory and clinical evidence, this review
      intends to discuss the effectiveness of Vitamin D supplements and controversy in
      clinical practice. The effect of Vitamin D in CKD patients is summarized in
      detail from CKD-mineral bone disease, the progression of renal function,
      cardiovascular events and immune system. Considerable disputes exist for the
      Vitamin D supplements in CKD, and a growing amount of experimental evidence and
      some clinical evidence are now gathering from in vitro, animal and
      epidemiological studies. 

PMID- 26211502
TI  - The amino acid mutations of the podocin in proteinuria: a meta-analysis.
AB  - While many previous studies have reported an association between the single
      nucleotide polymorphisms (SNPs) of the podocin and proteinuria occurred, a
      conclusive relationship has not been defined in every oligoallelic state of amino
      acid (AA) mutations in podocin. In this study, we performed a meta-analysis of
      the published data to investigate the impact of the oligoallelic AA mutations of
      the podocin on proteinuria; a total 16 AA mutations were investigated for
      oligoallelic pathogenicity. Despite significant heterogeneity within some of the
      comparisons, the results revealed significantly higher risks of proteinuria in
      early-onset (onset age <16) individuals for five mutations (P118L, R138Q, R168H,
      V180M, and V260E), and in all onset ages individuals for five mutations (R138Q,
      G140X, R229Q, V260E, and V290M) compared to non-variant individuals. We also
      tested the steroid response in individuals with R229Q and E237Q. No statistically
      significant differences in the two mutations carrier rate were observed between
      steroid resistance patients and controls. No AA mutation was selected for meta
      analysis on the recurrence of proteinuria after renal transplantation as lack of
      control data. In conclusion, our meta-analysis tested the pathogenicity of the
      oligoallelic AA mutations in podocin and suggested the potential causative
      mutations, and the alleles showing an association with protein susceptibility.
      The sensitivity and specificity of each causative mutation are pending further
      testing. 

PMID- 26211503
TI  - Chemical composition and biological evaluation of the volatile constituents from
      the aerial parts of Nephrolepis exaltata (L.) and Nephrolepis cordifolia (L.) C.
      Presl grown in Egypt.
AB  - The essential oil from the aerial parts of Nephrolepis exaltata and Nephrolepis
      cordifolia obtained by hydro-distillation were analyzed by gas chromatography/
      mass spectrometry. The essential oils exhibited potential antibacterial and
      antifungal activities against a majority of the selected microorganisms. NEA oil
      showed promising cytotoxicity in breast, colon and lung carcinoma cells. The
      results presented indicate that NEA oil could be useful alternative for the
      treatment of dermatophytosis. Comparative investigation of hydro-distilled
      volatile constituents from aerial parts (A) of Nephrolepis exaltata (NE) and
      Nephrolepis cordifolia (NC) (Family Nephrolepidaceae) was carried out. Gas
      chromatography/mass spectrometry revealed that oils differ in composition and
      percentages of components. Oxygenated compounds were dominant in NEA and NCA. 2,4
      Hexadien-1-ol (16.1%), nonanal (14.4%), beta-Ionone (6.7%) and thymol (2.7%) were
      predominant in NEA. beta-Ionone (8.0%), eugenol (7.2%) and anethol (4.6%) were
      the main constituents in NCA. Volatile samples were screened for their
      antibacterial and antifungal activities using agar diffusion method and minimum
      inhibitory concentrations. The cytotoxic activity was evaluated using viability
      assay in breast (MCF-7), colon (HCT-116) and lung carcinoma (A-549) cells by the
      MTT assay. The results revealed that NEA oil exhibited potential antimicrobial
      activity against most of the tested organisms and showed promising cytotoxicity. 

PMID- 26211504
TI  - Theory of mind selectively predicts preschoolers' knowledge-based selective word
      learning.
AB  - Children can selectively attend to various attributes of a model, such as past
      accuracy or physical strength, to guide their social learning. There is a debate
      regarding whether a relation exists between theory-of-mind skills and selective
      learning. We hypothesized that high performance on theory-of-mind tasks would
      predict preference for learning new words from accurate informants (an epistemic
      attribute), but not from physically strong informants (a non-epistemic
      attribute). Three- and 4-year-olds (N = 65) completed two selective learning
      tasks, and their theory-of-mind abilities were assessed. As expected, performance
      on a theory-of-mind battery predicted children's preference to learn from more
      accurate informants but not from physically stronger informants. Results thus
      suggest that preschoolers with more advanced theory of mind have a better
      understanding of knowledge and apply that understanding to guide their selection
      of informants. This work has important implications for research on children's
      developing social cognition and early learning. 

PMID- 26211505
TI  - Diagnostic performance of rapid diagnostic tests for the diagnosis of malaria at
      public health facilities in north-west Ethiopia.
AB  - OBJECTIVE: To assess the performance of RDTs against nested polymerase chain
      reaction (nPCR) for the diagnosis of malaria in public health facilities in north
      western Ethiopia. METHODS: Cross-sectional study at public health facilities in
      North Gondar, Ethiopia, of 359 febrile patients with signs and symptoms
      consistent with malaria. Finger prick blood samples were collected for testing in
      a P. falciparum/pan-malaria RDTs and for molecular analysis. Sensitivity,
      specificity and predictive values were determined for the RDTs using nPCR as
      reference diagnostic method. Kappa value was determined to demonstrate the
      consistency of the results between the diagnostic tools. RESULTS: By RDTs, 22.28%
      (80/359) of patients tested positive for malaria, and by nPCR, 27.02% (97/359)
      did. In nPCR, 1.67% (6/359) and 0.28% (1/359) samples were positive for P. ovale
      and P. malariae, which had almost all tested negative in the RDTs. The
      sensitivity, specificity, positive and negative predictive values of RDTs for the
      diagnosis of malaria were 62.9%, 92.7%, 76.3% and 87.1%, respectively, with 0.589
      measurement agreement between RDTs and nPCR. The sensitivity and specificity of
      RDTs for P. falciparum identification only were 70.8% and 95.2%, and 65.2% and
      93.1% for P. vivax. CONCLUSION: Although RDTs are commonly used at health posts
      in resource-limited environments, their sensitivity and specificity for the
      detection and species identification of Plasmodium parasites were poor compared
      to nPCR, suggesting caution in interpreting RDTs results. Particularly, in the
      light of expanded efforts to eliminate malaria in the country, more sensitive
      diagnostic procedures will be needed.

PMID- 26211506
TI  - How does practicing psychotherapy affect the personal life of the therapist? A
      qualitative inquiry of senior therapists' experiences.
AB  - OBJECTIVE: To investigate how psychotherapists' lives and relationships are
      influenced by their work. METHOD: Twelve senior psychotherapists took part in
      qualitative interviews. RESULTS: Thematic analysis yielded four significant
      themes: (i) it has been a privilege to know and contribute, and to be allowed to
      grow personally; (ii) facing suffering and destructiveness has been a burden;
      (iii) being a therapist has had an impact on my personal relationships-for better
      and worse; and (iv) I have needed to construct a way of living that allowed me to
      continue to do the work. CONCLUSION: Working as a therapist seem to imply a
      potential for developing openness, tolerance, and creativity, while being
      vulnerable to becoming overwhelmed with responsibility and feelings of
      inadequacy, isolation, and despair.

PMID- 26211507
TI  - South-East Asia study alliance guidelines on the management of acne vulgaris in
      South-East Asian patients.
AB  - The management of acne in South-East Asia is unique, as Asian skin and local
      variables require a clinical approach unlike that utilized in other parts of the
      world. There are different treatment guidelines per country in the region, and a
      group of leading dermatologists from these countries convened to review these
      guidelines, discuss current practices and recent advances, and formulate
      consensus guidelines to harmonize the management of acne vulgaris in the region.
      Emphasis has been placed on formulating recommendations to impede the development
      of antibiotic resistance in Propionibacterium acnes. The group adopted the Acne
      Consensus Conference system for grading acne severity. The group recommends that
      patients may be treated with topical medications including retinoids, benzoyl
      peroxide (BPO), salicylic acid, a combination of retinoid and BPO, or a
      combination of retinoids and BPO with or without antibiotics for mild acne;
      topical retinoid with topical BPO and a oral antibiotic for moderate acne; and
      oral isotretinoin if the patient fails first-line treatment (a 6- or 8-week trial
      of combined oral antibiotics and topical retinoids with BPO) for severe acne.
      Maintenance acne treatment using topical retinoids with or without BPO is
      recommended. To prevent the development of antibiotic resistance, topical
      antibiotics should not be used as monotherapy or used simultaneously with oral
      antibiotics. Skin care, comprised of cleansing, moisturizing and sun protection,
      is likewise recommended. Patient education and good communication is recommended
      to improve adherence, and advice should be given about the characteristics of the
      skin care products patients should use. 

PMID- 26211508
TI  - Clinical importance of re-interpretation of PET/CT scanning in patients referred
      to a tertiary care medical centre.
AB  - PURPOSE: To evaluate, in a controlled prospective manner with double-blind read,
      whether there are differences in interpretations of PET/CT scans at our tertiary
      medical centre, Rigshospitalet, compared to the external hospitals. METHODS:
      Ninety consecutive patients referred to our department who had an external F-18
      FDG PET/CT scan were included. Only information that had been available at the
      time of the initial reading at the external hospital was available at re
      interpretation. Teams with one radiologist and one nuclear medicine physician
      working side by side performed the re-interpretation in consensus. Two
      oncologists subsequently and independently compared the original reports with the
      re-interpretation reports. In case of 'major discordance', the oncologists
      assessed the respective reports validities. RESULTS: The interpretations were
      graded as 'accordant' in 43 patients (48%), 'minor discordance' in 30 patients
      (33%) and 'major discordance' in 17 patients (19%). In 11 (65%) of the 17 cases
      graded as 'major discordance', it was possible to determine which report that was
      most correct. In 9 of these 11 cases (82%), the re-interpretation was most
      correct; in one case, the original report and in another case, both
      interpretations were incorrect. CONCLUSIONS: Major discordant interpretations
      were frequent [19% (17 of 90 cases)]. In those cases where follow-up could assess
      the validity, the re-interpretation at Rigshospitalet was most correct in 9 of 11
      cases (82%), indicating that there is a difference in expertise in interpreting
      PET/CT at a tertiary referral hospital compared to primary local hospitals.

PMID- 26211509
TI  - Exacerbation of collagen antibody-induced arthritis in transgenic mice
      overexpressing peroxiredoxin 6.
AB  - OBJECTIVE: Peroxiredoxin 6 plays important and complex roles in the process of
      inflammation, but its role in the development of rheumatoid arthritis (RA)
      remains unclear. We undertook this study to investigate the roles and mechanisms
      of peroxiredoxin 6 in the development of collagen antibody-induced arthritis
      (CAIA) and antigen-induced arthritis (AIA) in peroxiredoxin 6-overexpressing
      transgenic mice, in peroxiredoxin 6-transfected RAW 264.7 cells, in macrophages
      isolated from peroxiredoxin 6-overexpressing transgenic mice, and in synoviocytes
      from arthritis patients. METHODS: CAIA and AIA were induced using standard
      methods. Peroxiredoxin 6-transfected RAW 264.7 cells, macrophages isolated from
      peroxiredoxin 6-overexpressing transgenic mice, and synoviocytes from arthritis
      patients were used to study proinflammatory responses and mechanisms. Clinical
      scores and histopathologic changes were determined in peroxiredoxin 6
      overexpressing transgenic mice and wild-type (WT) mice with CAIA or AIA.
      Generation of nitric oxide (NO), expression of inducible NO synthase and
      cyclooxygenase 2, and activity of NF-kappaB and activator protein 1 (AP-1) were
      determined in cultured macrophages and synoviocytes as well as in joint tissue
      from mice by Western blotting, electrophoretic mobility shift assay, and
      immunohistochemical analysis. RESULTS: Development of CAIA and AIA and
      proinflammatory responses were more exacerbated in peroxiredoxin 6-overexpressing
      transgenic mice than in WT mice. Overexpression of peroxiredoxin 6 increased
      lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells, in
      macrophages isolated from peroxiredoxin 6-overexpressing transgenic mice, and in
      synoviocytes from arthritis patients, and this was accompanied by up-regulation
      of the JNK pathway. Moreover, a JNK inhibitor completely blocked RA development
      and proinflammatory responses. CONCLUSION: Our findings suggest that
      overexpression of peroxiredoxin 6 might promote development of RA through NF
      kappaB and AP-1 activity via the JNK pathway.

PMID- 26211510
TI  - Reflex antenatal DNA screening for Down syndrome.

PMID- 26211511
TI  - Compensatory Changes in Calcium Metabolism Accompany the Loss of Vitamin D
      Receptor (VDR) From the Distal Intestine and Kidney of Mice.
AB  - 1,25 Dihydroxyvitamin D3 (1,25(OH)2 D) increases intestinal Ca absorption when
      dietary Ca intake is low by inducing gene expression through the vitamin D
      receptor (VDR). 1,25(OH)2 D-regulated Ca absorption has been studied extensively
      in the small intestine, but VDR is also present in the large intestine. Our goal
      was to determine the impact of large intestinal VDR deletion on Ca and bone
      metabolism. We used transgenic mice expressing Cre-recombinase driven by the 9.5
      kb human caudal type homeobox 2 (CDX2) promoter to delete floxed VDR alleles from
      the caudal region of the mouse (CDX2-KO). Weanling CDX2-KO mice and control
      littermates were fed low (0.25%) or normal (0.5%) Ca diets for 7 weeks. Serum and
      urinary Ca, vitamin D metabolites, bone parameters, and gene expression were
      analyzed. Loss of the VDR in CDX2-KO was confirmed in colon and kidney.
      Unexpectedly, CDX2-KO had lower serum PTH (-65% of controls, p < 0.001) but
      normal serum 1,25(OH)2 D and Ca levels. Despite elevated urinary Ca loss
      (eightfold higher in CDX2-KO) and reduced colonic target genes TRPV6 (-90%) and
      CaBPD9k (-80%) mRNA levels, CDX2-KO mice had only modestly lower femoral bone
      density. Interestingly, duodenal TRPV6 and CaBPD9k mRNA expression was fourfold
      and threefold higher, respectively, and there was a trend toward increased
      duodenal Ca absorption (+19%, p = 0.076) in the CDX2-KO mice. The major finding
      of this study is that large intestine VDR significantly contributes to whole-body
      Ca metabolism but that duodenal compensation may prevent the consequences of VDR
      deletion from large intestine and kidney in growing mice.

PMID- 26211513
TI  - A personal perspective of orphan drug development for rare diseases: A golden
      opportunity or an unsustainable future?

PMID- 26211512
TI  - Association of BMI with overall survival in patients with mCRC who received
      chemotherapy versus EGFR and VEGF-targeted therapies.
AB  - Although a raised body mass index (BMI) is associated with increased risk of
      colorectal cancer (CRC) and recurrence after adjuvant treatment, data in the
      metastatic setting is limited. We compared overall survival (OS) across BMI
      groups for metastatic CRC, and specifically examined the effect of BMI within the
      group of patients treated with targeted therapies (TT). Retrospective data were
      obtained from the South Australian Registry for mCRC from February 2006 to
      October 2012. The BMI at first treatment was grouped as underweight <18.5 kg/m(2)
      , Normal = 18.5 to <25 kg/m(2) , Overweight = 25 to <30 kg/m(2) , Obese I = 30 to
      <35 kg/m(2) , Obese II >=35 kg/m(2) . Of 1174 patients, 42 were underweight, 462
      overweight, 175 Obese I, and 77 Obese II. The OS was shorter for patients who
      were underweight and overweight compared to normal (OS 13.7 and 22.3 vs. 24.1
      months, respectively, hazard ratio [HR] 2.21 and 1.23). The adjusted median OS
      was longer for normal versus overweight or obese I patients receiving
      chemotherapy + targeted therapy (35.7 vs 25.1 or 22.8 months, HR 1.59 and 1.63,
      respectively) with no difference in OS for chemotherapy alone. On breakdown by
      type of targeted therapy, overweight and obese I patients had a poorer outcome
      with Bevacizumab. The BMI is predictive of a poorer outcome for underweight and
      overweight patients in the whole population. Of those receiving chemotherapy and
      targeted therapy, BMI is an independent predictor for OS for overweight and obese
      I patients, specifically for those treated with Bevacizumab. Patients who are
      overweight or obese (group I) may be a target group for lifestyle and nutrition
      advice to improve OS with TT. 

PMID- 26211514
TI  - Psycho-oncology and primary prevention in cancer control plans: an absent voice?
AB  - BACKGROUND: One third of cancer deaths are attributable to modifiable lifestyle,
      behaviour and psychosocial risk factors. Psycho-oncology can contribute
      significantly to prevention initiatives such as those described in national
      cancer control plans (NCCPs), to reduce or eliminate these risk factors. However,
      the extent to which psycho-oncology expertise has informed prevention objectives
      in plans is unclear. METHODS: Accordingly, 35 English language NCCPs were located
      via existing databases and were searched using Adobe text searches ('psycho',
      'social', 'behav' and 'intervention') to identify (a) representations of psycho
      oncology, its dimensions (psychological, social and behavioural) and roles (e.g.
      psychologist); and (b) behaviour/lifestyle change interventions. RESULTS: A third
      of NCCPs included the term psycho- or psychosocial-oncology; approximately half
      referred to a psycho-oncology dimension regarding prevention and early detection
      and half included actions/objectives relating to health professionals and
      provision of psychosocial care. The majority of cancer plans included prevention
      outcomes and focussed primarily on smoking cessation and alcohol reduction.
      Interventions commonly proposed were education, regulation and service provision;
      however, many were aspirational statements of intent rather than specific
      interventions. Psycho-oncology was represented in NCCPs but was limited in
      reference to prevention with few behavioural interventions utilised. CONCLUSIONS:
      Psycho-oncology input is needed to prescribe evidence-based interventions in
      cancer plans that not only educate, regulate and provide resources but also
      motivate, empower and create a supportive normative environment for behaviour
      change. In this manuscript, and throughout this Special Issue on Cancer
      Prevention, important principles, ideas and evidence within psycho-oncology are
      outlined which, if properly implemented, can help reduce the global cancer
      burden. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26211515
TI  - Rechargeable Hydrogen Storage System Based on the Dehydrogenative Coupling of
      Ethylenediamine with Ethanol.
AB  - A novel and simple hydrogen storage system was developed, based on the
      dehydrogenative coupling of inexpensive ethylenediamine with ethanol to form
      diacetylethylenediamine. The system is rechargeable and utilizes the same
      ruthenium pincer catalyst for both hydrogen loading and unloading procedures. It
      is efficient and uses a low catalyst loading. Repetitive reversal reactions
      without addition of new catalyst result in excellent conversions in both the
      dehydrogenation and hydrogenation procedures in three cycles. 

PMID- 26211516
TI  - Pharmacokinetic Profiles of Active Components After Oral Administration of a
      Kampo Medicine, Shakuyakukanzoto, to Healthy Adult Japanese Volunteers.
AB  - Shakuyakukanzoto (SKT), a traditional Japanese (Kampo) medicine, has been used by
      patients with muscle cramps and abdominal pains. In this trial, we analyzed
      plasma concentrations of active components after SKT was administered as a single
      oral dose of 2.5 or 5.0 g/day per person. The study was a randomized, open-label,
      two-arm, two-period, crossover trial conducted in healthy Japanese volunteers.
      Albiflorin (ALB), paeoniflorin (PAE), glycycoumarin (GCM), isoliquiritigenin
      (ILG), glycyrrhetic acid (GA), and glycyrrhetic acid-3-O-monoglucuronide were
      targeted, and the plasma concentration of each component was measured using a
      liquid chromatography-tandem mass spectrometry method. The pharmacokinetic
      parameters were calculated, and the linearity was assessed. All targeted
      components were detected in the plasma after oral administration of SKT. ALB,
      PAE, GCM, and ILG were detected at an early stage. The linearity was observed for
      the maximum plasma concentration of GCM, ILG, and GA and for the area under the
      plasma concentration-time curve of GA. In this trial, we demonstrated for the
      first time in humans that these components were absorbed into the blood after
      oral administration of SKT. The results of this pharmacokinetic trial in humans
      are also important and useful for understanding the mechanism of action of SKT,
      verifying the active components predicted in basic research, and conducting
      pharmacokinetics and safety studies in the future.

PMID- 26211517
TI  - Urinary prostaglandin D synthase as biomarker in lupus nephritis: a longitudinal
      study.
AB  - OBJECTIVES: Urinary prostaglandin D synthase (uPGDS) has been identified as a
      biomarker in lupus nephritis (LN) mice model as well as in humans. We studied the
      effect of therapy for LN on its levels in a longitudinal study and its ability to
      differentiate between active systemic lupus erythematosus (SLE) patients with and
      without nephritis. METHODS: Twenty-eight SLE patients with active LN, 6 patients
      with inactive disease, 12 patients with active non-renal disease and 19 healthy
      individuals were enrolled. Urine and serum samples were collected at baseline
      from all patients and at a 3-monthly follow-up from 25 patients in active
      nephritis group. uPGDS was measured by ELISA and normalised to urinary creatinine
      excretion. RESULTS: In the cross-sectional study, median uPGDS was higher in
      patients with active nephritis (618.5 ng/mg) as compared to healthy controls
      (141.7ng/mg; p<0.001), active non-renal (130.1ng/mg; p=0.008) and inactive
      disease (56.2 ng/mg; p=0.002) patients and had modest correlation with urinary
      protein / creatinine ratio (r=0.39; p=0.014). In the longitudinal study, median
      uPDGS reduced from 618.5 ng/mg at baseline (n=28) to 91.9 at 6 months (n=25),
      73.3 at 9 months (n=20) and 81.7 ng/mg at 12 months (n=13). uPGDS remained
      persistently elevated in a patient who developed CKD and showed an increase 2
      months before the clinical relapse in another patient with relapse of LN.
      CONCLUSIONS: Given that uPGDS levels fall after treatment of LN, uPGDS may be
      used to monitor the efficacy of therapy. It can also differentiate patients with
      active nephritis and active non renal lupus.

PMID- 26211518
TI  - Characterization of ecological risks from environmental releases of
      decamethylcyclopentasiloxane (D5).
AB  - Decamethylcyclopentasiloxane (D5) is used in personal care products and
      industrial applications. The authors summarize the risks to the environment from
      D5 based on multiple lines of evidence and conclude that it presents negligible
      risk. Laboratory and field studies show that D5 is not toxic to aquatic organisms
      or benthic invertebrates up to its solubility limit in water or porewater or its
      sorptive capacity in sediment. Comparison of lipid-normalized internal
      concentrations with measured concentrations in benthos indicates that field
      collected organisms do not achieve toxic levels of D5 in their tissues,
      suggesting negligible risk. Exposure to D5 resulted in a slight reduction of root
      biomass in barley at test concentrations 2 orders of magnitude greater than
      measured D5 levels in biosolids-amended soils and more than twice as high as the
      maximum calculated sorptive capacity of the soil. No effects were observed in
      soil invertebrates exposed to similar concentrations, indicating that D5 poses a
      de minimis risk to the terrestrial environment. High rates of metabolism and
      elimination of D5 compared with uptake rates from food results in biodilution in
      the food web rather than biomagnification, culminating in de minimis risk to
      higher trophic level organisms via the food chain. A fugacity approach
      substantiates all conclusions that were made on a concentration basis.

PMID- 26211519
TI  - Rational Tuning of the Electrocatalytic Nanobiointerface for a "Turn-Off" Biofuel
      Cell-Based Self-Powered Biosensor for p53 Protein.
AB  - Herein, a novel tunable electrocatalytic nanobiointerface for the construction of
      a high-sensitivity and high-selectivity biofuel-cell (BFC)-based self-powered
      biosensor for the detection of transcription factor protein p53 is reported, in
      which bilirubin oxidase (BOD)/DNA supramolecular modified graphene/platinum
      nanoparticles hybrid nanosheet (GPNHN) works as a new enhanced material of
      biocathode to control the attachment of target, and thus tune the electron
      transfer process of oxygen reduction for transducing signaling magnification. It
      is found that in the presence of p53, the strong interaction between the wild
      type p53 and its consensus DNA sequence on the electrode surface can block the
      electron transfer from the BOD to the electrode, thus providing a good
      opportunity for reducing the electrocatalytic activity of oxygen reduction in the
      biocathode. This in combination with the glucose oxidation at the carbon
      nanotube/Meldola's blue/glucose dehydrogenase bioanode can result in a current/or
      power decrease of BFC in the presence of wild-type p53. The specially designed
      BFC-based self-powered p53 sensor shows a wide linear range from 1 pM to 1 MUM
      with a detection limit of 1 pM for analyzing wild-type p53. Most importantly, our
      BFC-based self-powered sensors can detect the concentrations of wild-type p53 in
      normal and cancer cell lysates without any extensive sample
      pretreatment/separation or specialized instruments. The present BFC-based self
      powered sensor can provide a simple, economical, sensitive, and rapid way for
      analyzing p53 protein in normal and cancer cells at clinical level, which shows
      great potential for creating the treatment modalities that capitalize on the
      concentration variation of the wild-type p53.

PMID- 26211520
TI  - Pinensins: the first antifungal lantibiotics.
AB  - Lantibiotics (lanthionine-containing antibiotics) from Gram-positive bacteria
      typically exhibit activity against Gram-positive bacteria. The activity and
      structure of pinensin A (1) and B (2), lantibiotics isolated from a native Gram
      negative producer Chitinophaga pinensis are described. Surprisingly, the
      pinensins were found to be highly active against many filamentous fungi and
      yeasts but show only weak antibacterial activity. To the best of our knowledge,
      lantibiotic fungicides have not been described before. An in-depth bioinformatic
      analysis of the biosynthetic gene cluster established the ribosomal origin of
      these compounds and identified candidate genes encoding all of the enzymes
      required for post-translational modification. Additional encoded functions
      enabled us to build up a hypothesis for the biosynthesis, export, sensing, and
      import of this intriguing lantibiotic. 

PMID- 26211527
TI  - Editorial Comment on "The Risk of Damage to the Somatic Innervation of the Penis
      During the Advance Male Sling Procedure: an Anatomical Study".

PMID- 26211528
TI  - A basic dynamic transmission model of Staphylococcus aureus in the US population-
      ERRATUM.
AB  - doi: http://dx.doi.org/10.1017/S0950268813001106. Published online: 23 May 2013.
      In the above-mentioned article [1] the y axis in Figure 3a is incorrect. The
      correct version is given below. US pop. growth (estimated) (*108)

PMID- 26211529
TI  - [Therapeutic outcome of onabotulinum toxin type A in patients with upper limb
      spasticity].
AB  - Onabotulinum toxin type A treatment for post-stroke upper limb spasticity was
      investigated to contribute to establishing a standard dosage for Japanese
      patients. A total of 100 patients participated in the study. The outcome one
      month (33.6+/-6.5 days) after the treatment was assessed by the Modified Ashworth
      Scale (MAS) to estimate the mean effect with a 10-unit injection and the standard
      dosage expected to improve MAS 1 degree. Average improvement of 263 muscles
      treated with a higher concentration of 10 units diluted in 0.2 ml was 0.207+/
      0.414 degrees, and that of 231 muscles treated with a lower concentration of 10
      units in 0.4 ml was 0.149+/-0.244 degrees without significant difference among
      diluted concentrations. To improve MAS 1 degree, 64.6+/-31.1 units were required
      for the pectoralis major, 51.2+/-21.3 units for the teres major, 111.7+/-48.0
      units for the biceps brachii, 51.6+/-26.8 units for the brachioradialis, 54.1+/
      23.2 units for the brachialis, 34.4+/-10.7 units for the pronator teres, 64.6+/
      27.9 units for the flexor carpi radialis, 62.4+/-26.8 units for the flexor carpi
      ulnalis, 58.5+/-31.1 units for the flexor digitorum profundus, 69.7+/-35.1 units
      for the flexor digitorum superficialis, 24.6+/-13.4 units for the flexor pollicis
      longus, and 15.6+/-11.3 units for the adductor pollicis. Although the results
      shown here had no significant differences among concentrations, increasing the
      volume would disturb injection into small muscles, so we considered that a lower
      volume with a higher concentration should assure larger benefits. It is difficult
      to make effective injections into all spastic muscles within the officially
      permitted health insurance dosage of 240 units. Hence, it is advisable to
      increase the applicable upper limit based on safely achieved cumulative
      experience.

PMID- 26211530
TI  - The mediating role of mental toughness in sport.
AB  - AIM: We conducted two studies that examined different models, which included
      mental toughness and psychological constructs that have been found to be related
      to this construct. METHODS: In Study 1, 531 athletes completed measures of mental
      toughness, resilience, and emotional intelligence. In Study 2, 522 athletes
      completed measures of mental toughness, sport motivation, and self-efficacy.
      RESULTS: There were positive paths between the constructs in the model, which
      were mediated by mental toughness in Study 1. Further, there was a positive path
      between mental toughness and self-efficacy, but negative paths with introjected
      regulation and amotivation in Study 2. CONCLUSION: This two study paper suggests
      that it might also be the presence of constructs such as resilience, emotional
      intelligence, motivation, and/or self-efficacy that enable mentally tough
      individuals to excel under stressful circumstances rather than just coping.

PMID- 26211531
TI  - Randomized controlled resistance training based physical activity trial for
      central European nursing home residing older adults.
AB  - BACKGROUND: Nursing home residing older adults often experience fear of sickness
      or death, functional impairment and pain. It is difficult for these older adults
      to maintain a physically active lifestyle and to keep a positive outlook on life.
      This study evaluated the changes in quality of life, attitude to aging,
      assertiveness, physical fitness and body composition of nursing home residing
      elderly through a 15-week organized resistance training based physical activity
      program. METHODS: Inactive older adults living in a state financed nursing home
      (N.=45) were randomly divided into two intervention groups and a control group.
      Both intervention groups were assigned to two physical activity sessions a week,
      but one of these groups also had weekly discussions on health and quality of life
      (Mental group). Data on anthropometric measures, fitness performance, as well as
      quality of life and attitudes to aging survey data were collected. Due to low
      attendance rate 12 subjects were excluded from the analyses. Statistical analysis
      included Paired Samples t-tests and Repeated Measures Analysis of Variance.
      RESULTS: Both intervention groups significantly improved their social
      participation, and their upper- and lower-body strength scores. Also, subjects in
      the Mental group showed improvement in agility fitness test and certain survey
      scales. No positive changes were detected in attitude towards aging and body
      composition measures in any groups. The post-hoc results suggest that Mental
      group improved significantly more than the Control group. CONCLUSIONS: Regular
      physical activity with discussions on health and quality of life made a more
      meaningful difference for the older adults living in nursing home than physical
      activity alone. Due to the fact that all participants were influenced by the
      program, it is suggested to further explore this area for better understanding of
      enhanced quality of life.

PMID- 26211532
TI  - Genomic evidence of reactive oxygen species elevation in papillary thyroid
      carcinoma with Hashimoto thyroiditis.
AB  - Elevated levels of reactive oxygen species (ROS) have been proposed as a risk
      factor for the development of papillary thyroid carcinoma (PTC) in patients with
      Hashimoto thyroiditis (HT). However, it has yet to be proven that the total
      levels of ROS are sufficiently increased to contribute to carcinogenesis. We
      hypothesized that if the ROS levels were increased in HT, ROS-related genes would
      also be differently expressed in PTC with HT. To find differentially expressed
      genes (DEGs) we analyzed data from the Cancer Genomic Atlas, gene expression data
      from RNA sequencing: 33 from normal thyroid tissue, 232 from PTC without HT, and
      60 from PTC with HT. We prepared 402 ROS-related genes from three gene sets by
      genomic database searching. We also analyzed a public microarray data to validate
      our results. Thirty-three ROS related genes were up-regulated in PTC with HT,
      whereas there were only nine genes in PTC without HT (Chi-square p-value <
      0.001). Mean log2 fold changes of up-regulated genes was 0.562 in HT group and
      0.252 in PTC without HT group (t-test p-value = 0.001). In microarray data
      analysis, 12 of 32 ROS-related genes showed the same differential expression
      pattern with statistical significance. In gene ontology analysis, up-regulated
      ROS-related genes were related with ROS metabolism and apoptosis. Immune function
      related and carcinogenesis-related gene sets were enriched only in HT group in
      Gene Set Enrichment Analysis. Our results suggested that ROS levels may be
      increased in PTC with HT. Increased levels of ROS may contribute to PTC
      development in patients with HT. 

PMID- 26211533
TI  - Intrinsic and induced drug resistance mechanisms: in silico investigations at the
      cellular and tissue scales.
AB  - Multiple cellular drug resistance mechanisms are present in a broad range of
      tumour types and act to counteract the effects of drugs. There are independent
      mechanisms by which drug resistance occurs; these include (i) the multi-drug
      resistance mechanism involving upregulation of ABC transporter proteins and (ii)
      intracellular mechanisms which sequester/degrade/detoxify drugs. In addition,
      drug resistance mechanisms could be either intrinsic, or directly induced by the
      drug. In this paper we focus on the behaviour of intrinsic and induced variants
      of these resistance mechanisms in solid tumours, by systematically elucidating
      their cellular and tissue level effects with an aim to bridge the gap between
      cell and tissue levels. This is achieved in a controlled in silico setting, which
      allows for an investigation of the interplay between transport, resistance
      pathways, and tissue level effects. Overall the paper (i) provides insights into
      the tissue level functioning of widespread classes of intracellular resistance
      mechanisms, showing important differences, (ii) systematically elucidates the
      difference between intrinsic and induced drug resistance mechanisms at the cell
      and tissue levels, (iii) demonstrates how spatial heterogeneity in intrinsic
      resistance in cells can significantly affect the response of solid tumours to
      drugs, and (iv) examines how different independent resistance mechanisms work in
      concert, to counteract drug dosages in tumours. 

PMID- 26211534
TI  - Belagenpumatucel-L for the treatment of non-small cell lung cancer.
AB  - INTRODUCTION: Immunotherapy has become a promising approach for the treatment of
      NSCLC. In order to stimulate the host immune system against tumour antigens,
      several cancer vaccines have been generated and evaluated. Belagenpumatucel-L is
      a whole tumour cell vaccine expressing the antisense strand of the TGF-beta2
      gene. AREAS COVERED: The purpose of this article is to review the most relevant
      findings of clinical trials testing belagenpumatucel-L in advanced NSCLC
      patients. EXPERT OPINION: Although the Phase III trial investigating
      belagenpumatucel-L in stage III/IV patients did not meet its primary end point, a
      survival benefit was observed in several subgroups of patients. Further studies
      are needed in order to select patients who may benefit from this vaccine.

PMID- 26211536
TI  - You'll change more than I will: Adults' predictions about their own and others'
      future preferences.
AB  - It has been argued that adults underestimate the extent to which their
      preferences will change over time. We sought to determine whether such
      mispredictions are the result of a difficulty imagining that one's own current
      and future preferences may differ or whether it also characterizes our
      predictions about the future preferences of others. We used a perspective-taking
      task in which we asked young people how much they liked stereotypically young
      person items (e.g., Top 40 music, adventure vacations) and stereotypically old
      person items (e.g., jazz, playing bridge) now, and how much they would like them
      in the distant future (i.e., when they are 70 years old). Participants also made
      these same predictions for a generic same-age, same-sex peer. In a third
      condition, participants predicted how much a generic older (i.e., age 70) same
      sex adult would like items from both categories today. Participants predicted
      less change between their own current and future preferences than between the
      current and future preferences of a peer. However, participants estimated that,
      compared to a current older adult today, their peer would like stereotypically
      young items more in the future and stereotypically old items less. The fact that
      peers' distant-future estimated preferences were different from the ones they
      made for "current" older adults suggests that even though underestimation of
      change of preferences over time is attenuated when thinking about others, a bias
      still exists. 

PMID- 26211537
TI  - An Unusual Method of Suicidal Ligature Strangulation.
AB  - This article reports a case of suicidal strangulation by ligature of a 51-year
      old woman with a psychiatric disorder. She had been suffering from depression
      with a history of previous suicidal attempt. The deceased accomplished self
      strangulation using two ligatures, with one placed above the other and consisting
      of a satin fabric and a shoelace. The underlying shoelace ligature was fastened
      by a secure fixed square knot at the back of the neck. The overlying fabric piece
      was tied with a half-knot under the chin and was tightened around the neck
      manually. A detailed investigation and autopsy examination strongly suggests
      suicide. The case is of interest due to its rarity and uncommon method of
      execution. 

PMID- 26211538
TI  - Effect of ammonia-generating diet on ovine serum and follicular fluid ammonia and
      urea levels, serum oestrogen and progesterone concentrations and granulosa cell
      functions.
AB  - This study was undertaken to elucidate the effect of ammonia-generating diet on
      serum and follicular fluid ammonia and urea levels, serum oestrogen and
      progesterone concentrations and granulosa cell growth and secretion parameters in
      ewes (Ovis aries). Ewes were fed with 14% CP diet (control) or ammonia-generating
      diet or ammonia-generating diet plus soluble sugar. The serum and follicular
      fluid ammonia and urea level, serum oestrogen and progesterone levels and
      granulosa cell (obtained from ovaries of slaughtered ewes) growth parameters and
      secretory activities were estimated. Ammonia-generating diet (high-protein diet)
      increased the serum ammonia and urea concentration. Supplementation of soluble
      sugar significantly reduced the ammonia concentration in serum with comparable
      levels as in control group; however, the urea level in the same group was higher
      than that observed in control group. Supplementation of soluble sugar
      significantly reduced the follicular fluid ammonia concentration; however, the
      level was significantly higher compared to control group. Supplementation of
      soluble sugar brought down the follicular fluid urea level comparable to that
      observed in control group. Oestrogen and progesterone levels remained unchanged
      in ewes fed with different types of diet. Oestrogen and progesterone secretion
      were significantly lowered from granulosa cells recovered from ewes fed with high
      ammonia-generating diet. Low metabolic activity and high incidence of apoptosis
      were observed in granulosa cells obtained from ovaries of ewes fed with ammonia
      generating diet. 

PMID- 26211539
TI  - Prevention of treatment-related fluid overload reduces estimated effective cost
      of prothrombin complex concentrate in patients requiring rapid vitamin K
      antagonist reversal.
AB  - INTRODUCTION: Fresh frozen plasma (FFP) is a frequently used human blood product
      to reverse the effects of vitamin K antagonists. While FFP is relatively
      economical, its large fluid volume can lead to hospitalization complications,
      therefore increasing the overall cost of use. MATERIALS & METHODS: A recently
      published article by Sarode et al., in Circulation, described the rate of volume
      overload associated with FFP use for reversal of vitamin K antagonists. This
      condition, described as transfusion-associated circulatory overload, has a
      defined rate of intensive care admission, which also has a well-reported average
      cost. The additional monetary value of intensive care unit admission and caring
      for fluid overload is then compared to the cost of another product, four-factor
      prothrombin complex concentrates, which does not, as per the Sarode paper, result
      in fluid overload. RESULTS: The increased costs attributed to FFP-associated
      fluid overload for vitamin K antagonist reversal partly defrays the increased
      upfront cost of four-factor prothrombin complex concentrates. DISCUSSION: FFP is
      commonly used to acutely reverse the effects of vitamin K antagonists. However,
      its use requires significant time for infusion, may lead to fluid overload, and
      is not fully effective in compete anticoagulation reversal. One alternative
      therapy for anticoagulant reversal is use of prothrombin complex concentrates,
      which are rapidly infused, are not associated with fluid overload, and are
      effective in complete reversal of coagulation measurements. This should be
      considered for patients with acute bleeding emergencies.

PMID- 26211542
TI  - Problems With the Development and Validation of a Prognostic Model.

PMID- 26211543
TI  - Adaptation of a polyphagous herbivore to a novel host plant extensively shapes
      the transcriptome of herbivore and host.
AB  - Generalist arthropod herbivores rapidly adapt to a broad range of host plants.
      However, the extent of transcriptional reprogramming in the herbivore and its
      hosts associated with adaptation remains poorly understood. Using the spider mite
      Tetranychus urticae and tomato as models with available genomic resources, we
      investigated the reciprocal genomewide transcriptional changes in both spider
      mite and tomato as a consequence of mite's adaptation to tomato. We transferred a
      genetically diverse mite population from bean to tomato where triplicated
      populations were allowed to propagate for 30 generations. Evolving populations
      greatly increased their reproductive performance on tomato relative to their
      progenitors when reared under identical conditions, indicative of genetic
      adaptation. Analysis of transcriptional changes associated with mite adaptation
      to tomato revealed two main components. First, adaptation resulted in a set of
      mite genes that were constitutively downregulated, independently of the host.
      These genes were mostly of an unknown function. Second, adapted mites mounted an
      altered transcriptional response that had greater amplitude of changes when re
      exposed to tomato, relative to nonadapted mites. This gene set was enriched in
      genes encoding detoxifying enzymes and xenobiotic transporters. Besides the
      direct effects on mite gene expression, adaptation also indirectly affected the
      tomato transcriptional responses, which were attenuated upon feeding of adapted
      mites, relative to the induced responses by nonadapted mite feeding. Thus,
      constitutive downregulation and increased transcriptional plasticity of genes in
      a herbivore may play a central role in adaptation to host plants, leading to both
      a higher detoxification potential and reduced production of plant defence
      compounds. 

PMID- 26211540
TI  - Interrelatedness between dysbiosis in the gut microbiota due to immunodeficiency
      and disease penetrance of colitis.
AB  - The composition of the microbiome in health and disease has only recently become
      a major research focus. Although it is clear that an imbalance or dysbiosis in
      the microbiota is associated with disease, its interrelatedness to disease
      penetrance is largely unknown. Inflammatory bowel disease (IBD) is an excellent
      disease in which to explore these questions because of the extensive genetic
      studies identifying disease susceptibility loci and the ability to easily sample
      the intestinal microbiota in IBD patients due to the accessibility of stool
      samples. In addition, mouse models of IBD have contributed to our understanding
      of the interrelatedness of the gut microbiota and genes associated with IBD. The
      power of the mouse studies is that multiple colitis models exist that can be used
      in combination with genetically modified mice that harbour deficiencies in IBD
      susceptibility genes. Collectively, these studies revealed that bacterial
      dysbiosis does occur in human IBD and in mouse colitis models. In addition, with
      an emphasis on immune genes, the mouse studies provided evidence that specific
      immune regulatory proteins associated with IBD influence the gut microbiota in a
      manner consistent with disease penetrance. In this review, we will discuss
      studies in both humans and mice that demonstrate the impact of immunodeficiences
      in interleukin-10, interleukin-17, nucleotide-binding oligomerization domain
      (NOD) 2, NOD-like receptor proteins 3 and 6, Toll-like receptor or IgA have on
      the interrelatedness between the composition of the gut microbiota and disease
      penetrance of IBD and its mouse models. 

PMID- 26211552
TI  - Terror mismanagement: evidence that mortality salience exacerbates attentional
      bias in social anxiety.
AB  - Death anxiety is a basic fear underlying a range of psychological conditions, and
      has been found to increase avoidance in social anxiety. Given that attentional
      bias is a core feature of social anxiety, the aim of the present study was to
      examine the impact of mortality salience (MS) on attentional bias in social
      anxiety. Participants were 36 socially anxious and 37 non-socially anxious
      individuals, randomly allocated to a MS or control condition. An eye-tracking
      procedure assessed initial bias towards, and late-stage avoidance of, socially
      threatening facial expressions. As predicted, socially anxious participants in
      the MS condition demonstrated significantly more initial bias to social threat
      than non-socially anxious participants in the MS condition and socially anxious
      participants in the control condition. However, this effect was not found for
      late-stage avoidance of social threat. These findings suggest that reminders of
      death may heighten initial vigilance towards social threat.

PMID- 26211551
TI  - Role for engagement of beta-arrestin2 by the transactivated EGFR in agonist
      specific regulation of delta receptor activation of ERK1/2.
AB  - BACKGROUND AND PURPOSE: beta-Arrestins function as signal transducers linking
      GPCRs to ERK1/2 signalling either by scaffolding members of ERK1/2s cascades or
      by transactivating receptor tyrosine kinases through Src-mediated release of
      transactivating factor. Recruitment of beta-arrestins to the activated GPCRs is
      required for ERK1/2 activation. Our previous studies showed that delta receptors
      activate ERK1/2 through a beta-arrestin-dependent mechanism without inducing beta
      arrestin binding to the delta receptors. However, the precise mechanisms involved
      remain to be established. EXPERIMENTAL APPROACH: ERK1/2 activation by delta
      receptor ligands was assessed using HEK293 cells in vitro and male Sprague Dawley
      rats in vivo. Immunoprecipitation, immunoblotting, siRNA transfection,
      intracerebroventricular injection and immunohistochemistry were used to elucidate
      the underlying mechanism. KEY RESULTS: We identified a new signalling pathway in
      which recruitment of beta-arrestin2 to the EGFR rather than delta receptor was
      required for its role in delta receptor-mediated ERK1/2 activation in response to
      H-Tyr-Tic-Phe-Phe-OH (TIPP) or morphine stimulation. Stimulation of the delta
      receptor with ligands leads to the phosphorylation of PKCdelta, which acts
      upstream of EGFR transactivation and is needed for the release of the EGFR
      activating factor, whereas beta-arrestin2 was found to act downstream of the EGFR
      transactivation. Moreover, we demonstrated that coupling of the
      PKCdelta/EGFR/beta-arrestin2 transactivation pathway to delta receptor-mediated
      ERK1/2 activation was ligand-specific and the Ser(363) of delta receptors was
      crucial for ligand-specific implementation of this ERK1/2 activation pathway.
      CONCLUSIONS AND IMPLICATIONS: The delta receptor-mediated activation of ERK1/2 is
      via ligand-specific transactivation of EGFR. This study adds new insights into
      the mechanism by which delta receptors activate ERK1/2.

PMID- 26211553
TI  - Dynamic Contrast-Enhanced MRI Kinetic Parameters as Prognostic Biomarkers for
      Prediction of Survival of Patient with Advanced Hepatocellular Carcinoma: A Pilot
      Comparative Study.
AB  - RATIONALE AND OBJECTIVES: Tracer kinetic model selection for dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) data analysis influences its use as
      a prognostic biomarker. Our aim was to find DCE-MRI parameters that predict 1
      year survival (1YS) and overall survival (OS) among patients with advanced
      hepatocellular carcinoma (HCC) treated with antiangiogenic monotherapy by
      conducting a proof-of-concept comparative study of five different kinetic models.
      MATERIALS AND METHODS: Twenty patients with advanced HCC underwent DCE-MRI and
      subsequently received sunitinib. Pretreatment DCE-MRI data were analyzed
      retrospectively by using the Tofts-Kety (TK), extended TK, two compartment
      exchange, adiabatic approximation to the tissue homogeneity (AATH), and
      distributed parameter (DP) models. Arterial flow fraction (gamma), arterial blood
      flow (BFA), permeability-surface area product (PS), fractional interstitial
      volume (vI), and other five parameters were calculated for each model. Individual
      parameters were evaluated for 1YS prediction using cross-validated Kaplan-Meier
      analysis, and for association with OS using univariate Cox regression analysis,
      with additional permutation testing. RESULTS: For 1YS prediction, the TK model
      derived gamma (P = .007) and vI (P = .029) and the AATH model-derived PS (P =
      .005) were significant; all these parameters were lower in the high-risk group.
      Increase in the AATH model-derived PS and the DP model-derived BFA was associated
      with significant increase in OS with hazard ratios of 0.766 (P = .023) and 0.809
      (P = .025), respectively. CONCLUSIONS: The AATH model-derived PS was an effective
      prognostic biomarker for both 1YS and OS.

PMID- 26211554
TI  - Global Proteomic Analysis of Functional Compartments in Immature Avian Follicles
      Using Laser Microdissection Coupled to LC-MS/MS.
AB  - Laser microdissection (LMD) was utilized for the separation of the yolk,
      follicular wall (granulosa and theca), and surrounding stromal cells of small
      white follicles (SWF) obtained from reproductively active domestic fowl. Herein,
      we provide an in situ proteomics-based approach to studying follicular
      development through the use of LMD and mass spectrometry. This study resulted in
      a total of 2889 proteins identified from the three specific isolated
      compartments. White yolk from the smallest avian follicles resulted in the
      identification of 1984 proteins, while isolated follicular wall and ovarian
      stroma yielded 2470 and 2456 proteins, respectively. GO annotations highlighted
      the functional differences between the compartments. Among the three compartments
      examined, the relative abundance of vitellogenins, steroidogenic enzymes, anti
      Mullerian hormone, transcription factors, and proteins involved in retinoic acid
      receptors/retinoic acid synthesis, transcription factors, and cell surface
      receptors such as EGFR and their associated signaling pathways reflected known
      cellular function of the ovary. This study has provided a global proteome for
      SWF, white yolk, and ovarian stroma of the avian ovary that can be used as a
      baseline for future studies and verifies that the coupling of LMD with proteomic
      analysis can be used to evaluate proteins from small, physiologically functional
      compartments of complex tissue. 

PMID- 26211555
TI  - Body mass index, chronological age and hormonal status are better predictors of
      biological skin age than arm skin autofluorescence in healthy women who have
      never smoked.
AB  - BACKGROUND: As life expectancy is increasing and healthy ageing becomes more and
      more important, skin ageing is a growing topic of interest from both a medical
      and a commercial point of view. The urgency to unravel the causes of skin ageing
      is rising. However, there is a lack of objective, simple, noninvasive methods to
      assess biological skin age - a term introduced to describe how old someone looks,
      covering both the appearance and function of the skin. A rapid, noninvasive
      assessment of biological skin age would greatly facilitate the execution of the
      studies required to find the causes of skin ageing. OBJECTIVES: To find an
      objective, easy-to-apply method to assess biological skin age. METHODS: Skin age
      score (SAS) was compared with skin autofluorescence, a measure of advanced
      glycation end products in the skin, and several subject characteristics in 32
      healthy, white women with little sun-exposed skin and no history of smoking.
      RESULTS: A moderate, positive correlation (R(2) = 0.32, P = 0.001) between SAS
      and skin autofluorescence-based biological skin age was found. However, the
      variation in biological skin age according to SAS could be explained better by
      body mass index, chronological age and hormonal status (R(2) = 0.86, P < 0.001).
      CONCLUSIONS: In the current setting skin autofluorescence did not contribute
      better to the prediction of biological skin age than chronological age.
      Biological skin age was best predicted by body mass index, chronological age and
      hormonal status, and this approach provides a considerable simplification of the
      application of biological skin age.

PMID- 26211556
TI  - Breastfeeding and intelligence: a systematic review and meta-analysis.
AB  - AIM: This study was aimed at systematically reviewing evidence of the association
      between breastfeeding and performance in intelligence tests. METHODS: Two
      independent searches were carried out using Medline, LILACS, SCIELO and Web of
      Science. Studies restricted to infants and those where estimates were not
      adjusted for stimulation or interaction at home were excluded. Fixed- and random
      effects models were used to pool the effect estimates, and a random-effects
      regression was used to assess potential sources of heterogeneity. RESULTS: We
      included 17 studies with 18 estimates of the relationship between breastfeeding
      and performance in intelligence tests. In a random-effects model, breastfed
      subjects achieved a higher IQ [mean difference: 3.44 points (95% confidence
      interval: 2.30; 4.58)]. We found no evidence of publication bias. Studies that
      controlled for maternal IQ showed a smaller benefit from breastfeeding [mean
      difference 2.62 points (95% confidence interval: 1.25; 3.98)]. In the meta
      regression, none of the study characteristics explained the heterogeneity among
      the studies. CONCLUSION: Breastfeeding is related to improved performance in
      intelligence tests. A positive effect of breastfeeding on cognition was also
      observed in a randomised trial. This suggests that the association is causal.

PMID- 26211557
TI  - Cocktails and sunbeds: beware!

PMID- 26211563
TI  - Comparison of the Resistance of Teeth Instrumented with Different Nickel-Titanium
      Systems to Vertical Root Fracture: An In Vitro Study.
AB  - INTRODUCTION: This study compared the fracture resistance of teeth instrumented
      with ProTaper Universal (Dentsply Maillefer, Ballaigues, Switzerland), ProTaper
      Next (PTN, Dentsply Maillefer), WaveOne (Dentsply Maillefer), Twisted File
      (SybronEndo, Orange, CA), Mtwo (MT; VDW, Munchen, Germany), and Revo-S
      (MicroMega, Besancon, France) nickel-titanium systems and obturated with
      compatible gutta-percha cones of finishing files using the single-cone technique
      and a resin sealer. METHODS: The study included 72 mandibular premolar teeth. The
      roots were covered with additive silicone and placed in Eppendorf tubes, which
      were filled with a self-curing acrylic. The tubes were separated into 6 groups:
      prepared with the ProTaper Universal (F4 40/.06) (group 1), prepared with the PTN
      (X4 40/.06) (group 2), prepared with the WaveOne reciprocating file (40/.08)
      (group 3), prepared with the Twisted File (40/.04) (group 4), prepared with the
      MT (40/.06) (group 5), and prepared with the Revo-S (AS 40/.06) (group 6). After
      the preparations were completed, all the teeth were filled with the appropriate
      gutta-percha systems. The force (N) was applied at a 1-mm/min crosshead speed
      until the roots fractured. Differences among the groups were analyzed by Tukey
      and analysis of variance tests. RESULTS: Group 2 was the most resistant to
      fracture, and group 5 was the least resistant. The difference in the fracture
      resistance between the 2 groups was statistically significant (P = .019). The
      resistance of group 3 and group 6 to vertical root fracture was similar, and the
      resistance of group 4 was slightly lower than that of the other groups (P =
      .058). CONCLUSIONS: The roots instrumented with the MT were the least resistant,
      and the roots instrumented with the PTN were the most resistant to VRF.

PMID- 26211564
TI  - Constant Insertion Rate Methodology for Measuring Torque and Apical Force in 3
      Nickel-Titanium Instruments with Different Cross-sectional Designs.
AB  - INTRODUCTION: The aim of this study was to evaluate the cutting characteristics
      of 3 nickel-titanium instruments with different cross-sectional designs using a
      recently developed methodology. METHODS: Insertion tests at a constant rate of
      5.4 mm/min were performed on a bench test device by measuring the torque and
      apical force required for penetrating prefabricated acrylic blocks containing an
      artificial canal preflared with #10 and #15 K-files. Size 20/.06 Mtwo (VDW,
      Munich, Germany) and RaCe (FKG, La-Chaux De Fonds, Switzerland) instruments,
      together with ProTaper Universal (PTU) F1 instruments (Dentsply Maillefer,
      Ballaigues, Switzerland) (10 instruments of each type), were tested using an
      endodontic motor set at 300 rpm and 5 N.cm. The instruments were characterized
      with respect to the pitch length, rake angle, and cross-sectional area.
      Statistical analysis was performed with analysis of variance (alpha = 0.05).
      RESULTS: The torque was significantly lower for Mtwo compared with the other 2
      groups (P < .05). It was also lower for RaCe in comparison with PTU F1 (P < .05).
      Regarding the apical force, the RaCe instruments had lower values when compared
      with the Mtwo and PTU F1 instruments (P < .05). There was no statistically
      significant difference between the PTU F1 and Mtwo instruments (P > .05).
      CONCLUSIONS: The methodology allowed the cutting properties of the instruments to
      be assessed in terms of their different geometric characteristics. The cross
      sectional design, especially in Mtwo instruments with 2 sharp edges and great
      chip removal capability, was a differential factor for their higher cutting
      action.

PMID- 26211565
TI  - Patient-centered Outcomes of Root Canal Treatment: A Cohort Follow-up Study.
AB  - INTRODUCTION: This study aimed to evaluate the impact of pulpal pathology in
      terms of oral health-related quality of life and to evaluate root canal treatment
      in terms of pain during and at 7 days after treatment. METHODS: A consecutive
      sample of 250 adult patients requiring root canal treatment for a permanent tooth
      (incisors, canines, premolars, and molars) participated in this 1 week-follow-up
      study. The baseline impact regarding oral pain and well-being was recorded. After
      the root canal treatment had been performed, the pain and the comfort experienced
      during and 7 days after treatment were recorded on a 0-10 visual analog scale.
      Bivariate and multivariate analyses were performed to evaluate the modulating
      factors of pain. RESULTS: At baseline, 41.2% of the patients reported a lot of
      pain, and the severity of the pain and the functional limitation were
      significantly greater among men compared with women. During the procedure, 62% of
      patients did not feel any pain, and 95% were relatively comfortable during the
      intervention. After 7 days, 60.4% reported some kind of post-treatment pain
      although on average this was very slight (1.5 +/- 1.6 on a 0-10 range).
      Intrasubject comparisons revealed that the pain decreased progressively from the
      preoperative phase up to the postoperative phase, the pain being more acute in
      patients with vital teeth than those with necrotic pulps. CONCLUSIONS: The main
      impact on quality of life of pulpal pathology occurred in the pain and
      psychological discomfort dimensions. In more than 90% of patients undergoing root
      canal treatment, pain was totally or partially relieved after 7 days.

PMID- 26211566
TI  - Influence of Eugenol-based Sealers on Push-out Bond Strength of Fiber Post Luted
      with Resin Cement: Systematic Review and Meta-analysis.
AB  - INTRODUCTION: It is unclear in the literature if the presence of eugenol in root
      dentin impairs the retention of a fiber post luted with resin cements. The aim of
      this study was to systematically review the literature and perform meta-analysis
      on the influence of eugenol on the bond strength of posts luted to root canals.
      METHODS: A systematic electronic search was performed in PubMed, Scopus, Lilacs,
      and Web of Science databases. No language or publication date restrictions were
      applied. Eligible studies were those that assessed the immediate push-out bond
      strength of posts cemented to root dentin after the removal of eugenol-based
      sealer and compared it with a eugenol-free group. RESULTS: Thirteen studies met
      the inclusion criteria although 2 were excluded after full-text reading and 1
      study was identified by cross-reference. Nine studies were included in the meta
      analysis. Global analysis showed a significant influence of eugenol, which
      lowered the bond strength of fiber posts cemented to root canals (P < .001). The
      subgroup analysis carried out related to the different types of hybridization
      processes also indicated a negative effect of eugenol on bond strength in all
      subgroups assessed (P < .001). CONCLUSIONS: Eugenol-based sealer reduces the
      immediate push-out bond strength of fiber posts luted to root canal with resin
      cement, regardless of the type of adhesive system or resin cement used.

PMID- 26211567
TI  - Multicomponent Molecular Puzzles for Photofunction Design: Emission Color
      Variation in Lewis Acid-Base Pair Crystals Coupled with Guest-to-Host Charge
      Transfer Excitation.
AB  - Simple yet ubiquitous multimolecular assembly systems with color-tunable
      emissions are realized by cooperative electron donor-acceptor interactions, such
      as the boron-nitrogen (B-N) dative bond as a Lewis acid-base pair and charge
      transfer (CT) interactions. These are ternary-component systems consisting of a
      naphthalenediimide derivative (NDI), tris(pentafluorophenyl)borane (TPFB), and
      aromatic molecules (guest) with an NDI:TPFB:guest ratio of 1:2:2. The crystal
      shows guest-dependent color-tunable emissions such as deep blue to orange when a
      guest molecule of benzene is replaced with other pi-conjugated systems. A good
      correlation between the emission wavelength and ionization potential of the guest
      and electronic structure calculations indicated that the emission is due to the
      CT transition from the guest to the NDI. The present study suggests that a
      rational solution of multcomponent molecular puzzles would be useful for
      obtaining novel photofunctional solid-state systems. 

PMID- 26211568
TI  - Approaches to treatment 1: How is type 2 diabetes actually treated?

PMID- 26211569
TI  - Middle East respiratory syndrome coronavirus (MERS-CoV): A cluster analysis with
      implications for global management of suspected cases.
AB  - Since the initial description of the Middle East respiratory syndrome (MERS) in
      September 2012, a total of 1038 cases of MERS-CoV including 460 deaths have been
      reported from Saudi Arabia. From August 24, 2013 to September 3, 2013, a total of
      397 patients and contacts were tested for MERS-CoV. Of those tested, there were
      18 (4.5%) MERS-CoV cases reported in Al-Madinah al-Munawwarah with one large
      cluster. In this report, we describe the outcome, epidemiology and clinical
      characteristics of this cluster of which 4 cases involved healthcare workers.
      Fourteen cases appeared to be linked to one cluster involving healthcare workers
      (HCWs), family and patient contacts. Of the 18 cases, five (including 2 HCWs)
      were community acquired, two were household contacts, and 11 were healthcare
      associated (including 4 HCWs). All except 4 cases were symptomatic and the case
      fatality rate was 39% (7 of 18). The outbreak resulted in human to human
      transmission of an estimated 6 cases. Contact screening showed positive test in 1
      of 56 (1.8%) household contacts, and 3 of 250 (1.2%) HCWs. 

PMID- 26211571
TI  - Gastrobronchial fistula: A rare complication of sleeve gastrectomy.
AB  - Gastrobronchial fistula is a rare complication of sleeve gastrectomy. In this
      case presentation, the diagnosis of gastrobronchial fistula was made by
      endoscopic contrast injection into the fistulous tract. 

PMID- 26211570
TI  - Hepatitis B-related knowledge and vaccination in association with discrimination
      against Hepatitis B in rural China.
AB  - Hepatitis B virus (HBV) remains a challenging public-health issue in China.
      Hepatitis B carriers and patients suffer not only physically but also experience
      strong discrimination and stigma. China's rural population is 629 million. Thus,
      there is a great need to understand the situation surrounding HBV-related
      discrimination in everyday life in rural China. We studied 6,538 participants
      (>=18 y old) from 42 villages across 7 provinces (districts). Many studies have
      addressed discrimination against those with human immunodeficiency virus (HIV)
      and hepatitis C virus (HCV). However, few studies have addressed HBV-related
      discrimination. We found that the fear of HBV infection, not lack of knowledge
      about it, predominantly leads to HBV-related discrimination (although limited
      knowledge is also a cause). Notably, receiving the HBV vaccination contributes to
      reduced discrimination. In addition, the existence of fewer misunderstandings
      about false HBV transmission routes plays a more important role in discrimination
      than does understanding of true HBV transmission routes. Therefore, to reduce HBV
      related discrimination, policy makers should consider eliminating HBV-related
      fear, strengthening adult HBV immunization programs, developing large-scale
      education dissemination about HBV transmission routes and non-transmission
      routes, and paying greater attention to target populations. 

PMID- 26211572
TI  - Electroadsorption-assisted direct determination of trace arsenic without
      interference using transmission X-ray fluorescence spectroscopy.
AB  - An analytical technique based on electroadsorption and transmission X-ray
      fluorescence (XRF) for the quantitative determination of arsenic in aqueous
      solution with ppb-level limits of detection (LOD) is proposed. The approach uses
      electroadsorption to enhance the sensitivity and LOD of the arsenic XRF response.
      Amine-functionalized carbonaceous microspheres (NH2-CMSs) are found to be the
      ideal materials for both the quantitative adsorption of arsenic and XRF analysis
      due to the basic amine sites on the surface and their noninterference in the XRF
      spectrum. In electroadsorptive X-ray fluorescence (EA-XRF), arsenic is
      preconcentrated by a conventional three-electrode system with a positive
      electricity field around the adsorbents. Then, the quantification of arsenic on
      the adsorbents is achieved using XRF. The electroadsorption preconcentration can
      realize the fast transfer of arsenic from the solution to the adsorbents and
      improve the LOD of conventional XRF compared with directly determining arsenic
      solution by XRF alone. The sensitivity of 0.09 cnt ppb(-1) is obtained without
      the interferences from coexisted metal ions in the determination of arsenic, and
      the LOD is found to be 7 ppb, which is lower than the arsenic guideline value of
      10 ppb given by the World Health Organization (WHO). These results demonstrated
      that XRF coupled with electroadsorption was able to determine trace arsenic in
      real water sample. 

PMID- 26211573
TI  - A rare case of Epstein-Barr virus-associated leiomyosarcoma of the kidney in a
      patient with HIV.

PMID- 26211574
TI  - Decreased expression of PinX1 protein predicts poor prognosis of colorectal
      cancer patients receiving 5-FU adjuvant chemotherapy.
AB  - Previous studies suggest that Pin2/TRF1 interacting protein X1 (PinX1) is an
      intrinsic telomerase inhibitor and a putative tumor suppressor gene in human
      cancers. The aims of this study were to investigate PinX1 expression status in
      colorectal cancer (CRC) specimens and to clarify its clinical significance. A
      total of 83 CRC patients treated with radical resection and 5-fluorouracil (5-FU)
      based adjuvant chemotherapy were enrolled in this study. Immunohistochemistry was
      used to detect PinX1 and human telomerase reverse transcriptase (hTERT) protein
      expression in paired tumor and adjacent normal tissues. Results showed that PinX1
      expression was significantly reduced in tumor tissues as compared to normal
      tissues, the rate of PinX1 protein low/negative expression in CRC and normal
      tissues was 43.4% (36/83) and 9.6% (8/83), respectively (P<0.001), while hTERT
      protein expression was upregulated in CRC and negative correlated with PinX1
      expression. Although no correlations with clinicopathological features, PinX1
      downregulation was significantly associated with adverse 5-year overall survival
      (OS) and disease-free survival (DFS). Cox proportional hazards model further
      revealed that PinX1 expression was an independent factor in predicting OS and DFS
      for CRC patients, apart from lymph metastasis. In conclusion, PinX1 protein
      expression is decreased in CRC, which may be a new promising tumor marker for CRC
      prognosis and 5-FU chemosensitivity. 

PMID- 26211575
TI  - Improved anti-melanoma effect of a transdermal mitoxantrone ethosome gel.
AB  - Melanomas are malignant tumors characterized by early metastasis, rapid
      development, poor prognosis and high mortality. A highly effective and convenient
      method is necessary for long-term treatment of melanomas. Mitoxantrone (MTO) was
      topically applied for melanoma therapy using an MTO ethosome gel. Firstly, an
      ethosome was prepared from MTO, phospholipids, ethanol and water followed by
      addition of hydroxypropyl methylcellulose to obtain an ethosome gel. The ethosome
      was characterized. The cytotoxicity on B16 melanoma cells was evaluated on an
      electrical cell-substrate impedance sensing system with a novel modified chip. In
      vivo anti-melanoma effect of the ethosome gel was explored. Immunohistochemical
      and flow cytometric investigations were done. The MTO ethosomes had the size of
      78nm and the zeta potential of -55mV. The ethosomes were flexible vesicles and
      showed much higher in vitro permeability across the rat skin than MTO aqueous
      solutions. The ethosomes had significant cytotoxicity and higher in vivo anti
      melanoma effect than MTO solutions. The calreticulin membrane translocation of
      B16 cells was improved by the MTO ethosomes and the cell uptake of MTO was
      confirmed. The MTO ethosome gel is a promising transdermal delivery system for
      melanoma therapy with the advantages of non-invasion and no significant side
      effects. 

PMID- 26211576
TI  - Knockdown of type I insulin-like growth factor receptor inhibits human colorectal
      cancer cell growth and downstream PI3K/Akt, WNT/beta-catenin signal pathways.
AB  - Type I insulin-like growth factor receptor (IGF1R) signal is involved in normal
      physiology and many disease progressions. In this study, we presented the role of
      IGF1R in colorectal cancer cell lines. Results showed that knockdown of IGF1R
      using small interfering RNA in HT-29, SW620 cells strongly inhibited cell
      proliferation, arrested cell cycle and also promoted cell apoptosis. Western
      blotting results indicated that the downstream PI3K/Akt and canonical WNT signal
      pathways were blocked. In addition, we observed that reduction of IGF1R
      suppressed the expression of many inflammatory factors, such as NF-kappaB, p-NF
      kappaB, COX-2 and iNOS. Together, this study demonstrate that knockdown of IGF1R
      inhibits CRC cells growth and provides an additional evidence for further
      clarifying the mechanism of IGF1R involved in CRC and inflammation-induced
      tumorigenesis. 

PMID- 26211577
TI  - The effect of adjuvant chemotherapy on plasma TAT and F 1+2 levels in patients
      with breast cancer.
AB  - INTRODUCTION: Increased thromboembolic disorders and chemotherapy-induced
      thromboembolic events are well known phenomena in patients with breast cancer.
      Antithrombin III (AT III) inactivates thrombin, resulting in increased thrombin
      antithrombin (TAT) levels. Activated factor X cleaves prothrombin and thrombin,
      resulting in increased levels of prothrombin fragment 1+2 (F 1+2). Increased TAT
      and F 1+2 levels show coagulation activation. The aim of this study was to
      examine plasma levels of TAT and F 1+2 and the effect of anthracycline-based
      chemotherapy on plasma TAT and F 1+2 in patients with operable breast cancer.
      MATERIALS AND METHODS: Seventy patients and 30 age-matched healthy controls were
      enrolled. Levels of TAT and F 1+2 were investigated before and after adjuvant
      chemotherapy. Basal levels (pre-chemotherapy) of TAT and F 1+2 in patients were
      compared with those in healthy controls and patient levels after 3 cycles of
      chemotherapy. Levels of TAT and F 1+2 were determined using the ELISA method.
      RESULTS: TAT and d-dimer levels were significantly higher in patients, (P: 0.02
      and P<0.001, respectively). Post-chemotherapy F 1+2 levels were higher than basal
      levels (P: 0.02). F 1+2 levels were higher in patients, although the difference
      was not statistically significant (P: 0.52). There was no difference between
      basal and post-chemotherapy TAT levels. DISCUSSION: In conclusion, while higher
      post-chemotherapy F 1+2 levels suggest that the cumulative effect of chemotherapy
      increases the risk of thrombosis, TAT and d-dimer levels indicate that the effect
      of the cancer further increases the risk of thrombosis in patients with operable
      breast cancer.

PMID- 26211578
TI  - The single nucleotide polymorphism and haplotype analysis of MDR1 in Chinese
      diffuse large B cell lymphoma patients.
AB  - We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide
      polymorphism (SNP) and haplotype variants were associated with the susceptibility
      to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208
      healthy controls from Jiangsu Han population were enrolled in this study. They
      were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP)
      method or DNA direct sequencing at three common loci: C1236T, G2677T/A and
      C3435T. At locus G2677T/A, allele G and genotype GT were significantly more
      common in DLBCL (G: OR=1.48, 95% CI: 1.08-2.02, Pc=0.03; GT: OR=1.96, 95% CI:
      1.25-3.07, Pc<0.01), while genotype AT in this locus seemed to be protective
      (OR=0.29, 95% CI: 0.02-0.72, Pc=0.03). TT genotype at locus C3435T showed a risk
      factor in DLBCL (OR=2.38, 95% CI: 1.52-3.74, Pc<0.01). The frequency of T-G-T
      haplotype was significantly increased in DLBCL group (OR=5.21, 95% CI: 2.58
      10.54, Pc<0.01); haplotype of G-T in 2677-3435 and diplotype of 2677GT/3435TT
      were significantly more frequent in DLBCL group (G-T: OR=3.97, 95% CI: 2.31-6.85,
      Pc<0.01; 2677GT/3435TT: OR=4.55, 95% CI: 2.02-10.22, Pc<0.01). Our findings
      demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute
      to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677-3435
      and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective
      genotype. These findings could provide evidence that the MDR1 SNPs may modify the
      susceptibility to DLBCL and shade new lights in disease association studies. 

PMID- 26211579
TI  - Modulating the SDF-1/CXCL12-induced cancer cell growth and adhesion by sulfated
      K5 polysaccharides in vitro.
AB  - Stromal cell-derived factor-1 (SDF-1)/chemokine (CXC motif) ligand 12 (CXCL12) is
      involved in the process of tumor progression. Sulfated K5 polysaccharides have
      shown anti-cancer activity by acting on multiple targets, though it remains
      unclear whether sulfated K5 polysaccharides would disrupt SDF-1/CXCL12-stimulated
      cancer biology. This study aimed to investigate the effects of sulfated K5
      polysaccharides on cell growth, adhesion in murine B16 melanoma cells and the
      underlying mechanism by targeting SDF-1/CXCL12. Results indicated that K5-NS,OS
      inhibited the proliferation of B16 melanoma cells, induced the cell cycle arrest
      mainly at the G0/G1 phase, and suppressed cancer cell proliferation or adhesion
      induced by SDF-1/CXCL12. It was possible that K5-NS,OS appeared to interact with
      CXCL12 and block the subsequent biological functions. This work suggests that the
      existence of O- and N-sulfate groups is more effective in targeting CXCL12 and
      exhibiting anti-cancer activity. 

PMID- 26211580
TI  - The association of DNA methyltransferase 1 gene polymorphisms with susceptibility
      to childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: It has been suggested that aberrant DNA methylation is a common
      epigenetic alteration in malignancies. Genetic variations in DNA
      methyltransferase 1 gene (DNMT1), which encodes the maintenance
      methyltransferase, have been demonstrated to be involved in cancer
      susceptibility. In the present study, we investigated whether genetic
      polymorphisms in DNMT1 could be associated with risk of childhood acute
      lymphoblastic leukemia (ALL) in a Chinese population. METHODS: We selected seven
      tagging single-nucleotide polymorphisms (tagSNPs, rs11880388, rs10423341,
      rs7253062, rs11085721, rs2228611, rs2228612 and rs16999593) in DNMT1 and
      genotyped these SNPs by using TaqMan method in a case-control study of 377
      patients with ALL and 500 healthy controls. The logistic regression was used to
      assess the genetic associations with occurrence of ALL with adjustment for
      possible confounders. RESULTS: We found that one (rs11085721) of the seven
      tagSNPs was significantly associated with the risk of ALL. Compared with
      individuals' with DNMT1 rs11085721 GG genotype, those subjects carrying the
      rs11085721 GT genotypes were associated with significantly increased risk for ALL
      (GT vs. GG:OR=1.29, 95% CI=1.10-1.51). Similar association was also observed when
      combined the individuals with rs11085721 GT and rs11085721 TT genotypes (GT/TT
      vs. TT:OR=1.29, 95% CI=1.10-1.50). No positive results were observed for the
      other tagSNPs. CONCLUSIONS: Our results suggest that the DNMT1 rs11085721
      polymorphism may confer susceptibility to ALL in the Chinese population. The
      initial findings should be validated by large population-based prospective
      studies in the future.

PMID- 26211581
TI  - The inhibitory effects of xanthohumol, a prenylated chalcone derived from hops,
      on cell growth and tumorigenesis in human pancreatic cancer.
AB  - Pancreatic cancer (PC) is one of the most lethal human malignancies worldwide.
      Here, we demonstrated that xanthohumol (XN), the most abundant prenylated
      chalcone isolated from hops, inhibited the growth of cultured PC cells and their
      subcutaneous xenograft tumors. XN treatment was found to induce cell cycle arrest
      and apoptosis of PC cells (PANC-1, BxPC-3) by inhibiting phosphorylation of
      signal transducer and activator of transcription 3 (STAT3) and expression of its
      downstream targeted genes cyclinD1, survivin, and Bcl-xL at the messenger RNA
      level, which involved in regulation of apoptosis and the cell cycle. Overall, our
      results suggested that XN presents a promising candidate therapeutic agent
      against human PC and the STAT3 signaling pathway is its key molecular target. 

PMID- 26211582
TI  - Novel drug delivery liposomes targeted with a fully human anti-VEGF165 monoclonal
      antibody show superior antitumor efficacy in vivo.
AB  - Immunoliposomes modified by monoclonal antibodies are promising agents for tumor
      targeted drug delivery. Here, we designed a novel long-circulating liposome
      conjugated to a fully human anti-vascular endothelial growth factor (VEGF)
      monoclonal antibody (mAb) as a targeting modification. VEGF mAb selectively
      accumulates in tumor tissue over-expressing VEGF; therefore, drugs accumulate
      within tumors to enhance antitumor efficacy. For this study, paclitaxel (PTX), a
      chemotherapeutic agent with potent antiangiogenic activity, was used as a
      prototype drug. PEGylated liposomes loaded with paclitaxel were successfully
      prepared using the thin-film hydration method with appropriate amounts of S100PC,
      cholesterol, and mPEG2000-DSPE at a molar ratio of 90:10:5. The VEGF mAb was then
      conjugated to the Mal-PEG2000-DSPE liposome at a ratio of 6.65mg of VEGF
      mAb/MUmol Mal-PEG2000-DSPE, producing completely stable VEGF mAb-liposomes. The
      anticancer activity was evaluated in BALB/c nude mice bearing SGC-7901
      xenografts. The results indicate that VEGF-targeted mAb-liposomes are visualized
      in the interior of the tumor and taken up by tumor cells. After receiving five
      i.v. injections, the mice treated with mAb-liposomal paclitaxel showed superior
      anticancer activity than the commercial formulation Taxol((r)) and unmodified
      liposomal formulations. Immunohistochemical analysis of the tumor tissues showed
      weaker VEGF and CD31 signals in mAb-liposome-treated tumors compared to treatment
      with no mAb-liposomes. Immunohistology analysis results demonstrated that the
      tumors treated with VEGF mAb-liposomes had the lowest concentration of Ki67
      labeled cells and the greatest number of TUNEL-positive cells. All data showed
      that the novel VEGF mAb-liposomes carried anticancer drugs, such as paclitaxel,
      to the interior of solid tumors and inhibited tumor growth effectively. 

PMID- 26211583
TI  - The HLA-DQB1 gene polymorphisms associated with cervical cancer risk: A meta
      analysis.
AB  - Human leukocyte antigens (HLA) alleles may affect the development of cervical
      cancer through immunologic control of human papillomavirus (HPV). The association
      between HLA-DQB1 alleles and risk of cervical cancer has been extensively
      studied, but the results obtained remain inconsistent. To explore a more
      extensive role of HLA-DQB1 alleles on cervical cancer risk, we carried out a meta
      analysis including 4862 cases and 8988 controls from 22 published studies. Odds
      ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength
      of the association. The overall results suggested that HLA-DQB1*02 (OR=0.91, 95%
      CI=0.82-0.99), *03 (OR=0.85, 95% CI=0.74-0.97) and *0603 (OR=0.62, 95% CI=0.53
      0.72) had a significantly association with decreased cervical cancer risk. In
      contrast, DQB1*05 (OR=1.18, 95% CI=1.01-1.38), *0301 (OR=1.14, 95% CI=1.06-1.23)
      and *0402 (OR=1.31, 95% CI=1.04-1.64) conferred a significantly higher risk to
      cervical cancer. Moreover, a significantly association with increased or
      decreased cervical cancer risk was found among Europeans and Asians after
      stratification of the HLA-DQB1 alleles by ethnicity. These findings supported
      that the HLA-DQB1 alleles may contribute to genetic susceptibility of cervical
      cancer. Further studies with a greater number of cases are expected to confirm
      our results. 

PMID- 26211584
TI  - Molecular docking of chemotherapeutic agents to CYP3A4 in non-small cell lung
      cancer.
AB  - CYP3A4, a "heme" containing isoform, abundantly found in the liver, gastro
      intestinal tract, lungs and renal cells, also known as drug metabolising enzyme
      (DME) may be responsible for the disease progression in cancers such as lung
      cancer. Hence, we have targeted this protein for improving drug selection and in
      preventing adverse reactions. The aim of this study was to examine
      chemotherapeutic drug binding to CYP3A4 and the interactions therein. We have
      used Schrodinger suite 2014, to perform molecular docking of human CYP3A4, by
      Induced Fit Docking using gemcitabine, cisplatin, carboplatin, docetaxel and
      paclitaxel drugs. We evaluated drug-binding affinities using Prime/MMGBSA and
      using these scores we compared the affinities of combination therapies against
      CYP3A4. Analysis of the docking results showed gemcitabine>carboplatin>cisplatin
      as the order of binding affinities, with gemcitabine having the best docking
      score. Interestingly, docetaxel and paclitaxel did not bind to CYP3A4*1B. The
      combination drug-binding affinity analysis showed gemcitabine+carboplatin to have
      the best docking score and hence, efficacy. Our investigation has identified the
      residue Arg 105 to be more frequently involved in drug binding to CYP3A4. Our
      results suggest that gemcitabine or combination of gemcitabine+carboplatin could
      serve as an excellent therapy against CYP3A4 in NSCLC patients. Thus, our study
      depicts binding of chemotherapeutic drugs to CYP3A4 and has identified the
      residues that may be targeted for therapy in NSCLC patients. 

PMID- 26211585
TI  - The clinical significance of FSCN1 in non-small cell lung cancer.
AB  - Fascin actin-bundling protein 1 (FSCN1) plays significant roles in biological
      processes such as tumor cell invasion and metastasis. However, little is known
      about prognostic value of FSCN1 in non-small cell lung cancer (NSCLC). FSCN1 mRNA
      and protein expression were detected by real-time PCR and Western blot in NSCLC
      tissues and paired adjacent normal lung tissues. Furthermore, the association of
      FSCN1 protein expression with clinicopathological characteristics including the
      survival was explored in 156 NSCLC patients. In our results, FSCN1 mRNA and
      protein expression were obviously higher in NSCLC tissues than in normal lung
      tissues. High levels of FSCN1 protein were positively correlated with status of
      differentiated degree, clinical stage, N classification, and M classification in
      NSCLC. Meanwhile, higher FSCN1 protein expression was significantly associated
      with poor overall survival in patients with NSCLC. Multivariate analyses showed
      that increased FSCN1 protein expression was a poor independent prognostic
      biomarker for NSCLC patients. In conclusions, FSCN1 plays an important role on
      NSCLC progression and prognosis and may serve as a convictive prognostic
      biomarker for NSCLC patients. 

PMID- 26211586
TI  - Cerium oxide nanoparticles alleviate oxidative stress and decreases Nrf-2/HO-1 in
      D-GALN/LPS induced hepatotoxicity.
AB  - Translocation of the master regulator of antioxidant-response element-driven
      antioxidant gene, nuclear factor erythroid 2 (Nrf-2) from the cytoplasm into the
      nucleus and triggering the transcription of hemoxygenase-1 (HO-1) to counteract
      the oxidative stress is a key feature in D-galactoseamine and lipopolysaccharide
      (D-GALN/LPS) induced hepatotoxicity. We mainly aimed to study the effect of
      cerium oxide (CeO2) nanoparticles on Nrf-2/HO-1 pathway whereas; it has
      previously shown to have an antioxidant effect in liver models. Administration of
      CeO2 nanoparticles significantly decreased the translocation of the cytoplasmic
      Nrf-2 with a concomitant decrement in the gene expression of HO-1 as it reveals a
      powerful antioxidative effect as indicated by the significant increase in the
      levels of glutathione (GSH), glutathione peroxidase (GPX1), glutathione reductase
      (GR), superoxide dismutase (SOD) and catalase. In synchronization, a substantial
      decrement in the levels of inducible nitric oxide synthase (iNOS), TBARS and
      percentage of DNA fragmentation was established. These results were confirmed by
      histopathology examination which showed a severe degeneration, haemorrhages,
      widened sinusoids and focal leukocyte infiltration in D-GALN/LPS treatment and
      these features were alleviated with CeO2 administration. In conclusion, CeO2 is a
      potential antioxidant that can effectively decrease the translocation of the
      cytoplasmic Nrf-2 into the nucleus and decrease HO-1 in D-GALN/LPS induced
      hepatotoxicity. 

PMID- 26211588
TI  - Increased expression of proline-, glutamic acid- and leucine-rich protein PELP1
      in non-small cell lung cancer.
AB  - It has been demonstrated that estrogens are able to enhance lung tumorigenesis by
      estrogen receptor (ER) pathway. ER signaling is a highly complex process that
      requires a number of different coactivators, including proline-, glutamic acid-
      and leucine-rich protein-1 (PELP1). We studied PELP1 transcript and protein
      levels in cancerous and histopathologically unchanged lung tissues obtained from
      73 patients diagnosed with non-small cell lung cancer (NSCLC). We observed
      increased levels of PELP1 transcript (P=0.00001) and protein (P=0.00001) in tumor
      tissues compared to adjacent histopathologically unchanged tissues. Significant
      increase of PELP1 transcript/protein level was found in all patients, regardless
      of gender (males: P=0.0003/P=0.000003; females: P=0.0005/P=0.02), age (<= 60
      patients: P=0.042/P=0.016; >60 patients: P=0.00001/P=0.00001) or
      histopathological type of tumor (adenocarcinoma [ADC]: P=0.004/P=0.0006; squamous
      cell carcinoma [SSC]: P=0.0009/P=0.0008). Increased PELP1 transcript/protein
      levels were also correlated with some lung cancer stage (1a: P=0.07/P=0.02; 1b:
      P=0.001/P=0.03; 2a: P=0.012/P=0.001), tumor size (T2a: P=0.0006/P=0.001) and
      lymph node metastasis (N0: P=0.0003/P=0.0006; N1: P=0.017/P=0.003). Moreover,
      significant increase in PELP1 transcript level in cancer stage 1a (P=0.02) was
      observed. PELP1 protein content was higher in tumor tissues of patients with
      cancer stage 3a (P=0.04) and in T1a tumor size (P=0.03). Our studies demonstrate
      significantly higher amounts of PELP1 transcript and protein in tumor tissues in
      patients with NSCLC. Moreover, we also determined the association of PELP1
      transcript and protein level with some clinicopathological features of NSCLC. 

PMID- 26211587
TI  - Induction of cytosine arabinoside-resistant human myeloid leukemia cell death
      through autophagy regulation by hydroxychloroquine.
AB  - We investigated the effects of the autophagy inhibitor hydroxychloroquine (HCQ)
      on cell death of cytosine arabinoside (Ara-C)-resistant human acute myeloid
      leukemia (AML) cells. Ara-C-sensitive (U937, AML-2) and Ara-C-resistant (U937/AR,
      AML-2/AR) human AML cell lines were used to evaluate HCQ-regulated cytotoxicity,
      autophagy, and apoptosis as well as effects on cell death-related signaling
      pathways. We found that HCQ-induced dose- and time-dependent cell death in Ara-C
      resistant cells compared to Ara-C-sensitive cell lines. The extent of cell death
      and features of HCQ-induced autophagic markers including increase in microtubule
      associated protein light chain 3 (LC3) I conversion to LC3-II, beclin-1, ATG5, as
      well as green fluorescent protein-LC3 positive puncta and autophagosome were
      remarkably greater in U937/AR cells. Also, p62/SQSTM1 was increased in response
      to HCQ. p62/SQSTM1 protein interacts with both LC3-II and ubiquitin protein and
      is degraded in autophagosomes. Therefore, a reduction of p62/SQSTM1 indicates
      increased autophagic degradation, whereas an increase of p62/SQSTM1 by HCQ
      indicates inhibited autophagic degradation. Knock down of p62/SQSTM1 using siRNA
      were prevented the HCQ-induced LC3-II protein level as well as significantly
      reduced the HCQ-induced cell death in U937/AR cells. Also, apoptotic cell death
      and caspase activation in U937/AR cells were increased by HCQ, provided evidence
      that HCQ-induced autophagy blockade. Taken together, our data show that HCQ
      induced apoptotic cell death in Ara-C-resistant AML cells through autophagy
      regulation. 

PMID- 26211589
TI  - Sickle cell anemia induces changes in peripheral lymphocytes E-NTPDase/E-ADA
      activities and cytokines secretion in patients under treatment.
AB  - Sickle cell anemia (SCA) is characterized by hemoglobin polymerization that
      results in sickle-shaped red blood cells. The vascular obstruction by sickle
      erythrocytes is often inflammatory, and purinergic system ecto-enzymes play an
      important role in modulating the inflammatory and immune response. This study
      aimed to evaluate the E-NTPDase and E-ADA activities in lymphocytes of SCA
      treated patients, as well as verify the cytokine profile in this population.
      Fifteen SCA treated patients and 30 health subjects (control group) were
      selected. The peripheral lymphocytes were isolated and E-NTPDase and E-ADA
      activities were determined. Serum was separated from clot formation for the
      cytokines quantification. E-NTPDase (ATP and ADP as substrate) and E-ADA
      (adenosine as substrate) activities were increased in lymphocytes from SCA
      patients (P<0.001). The TNF-alpha and IL-6 serum cytokines showed decreased on
      SCA patients comparing to control (P<0.001). The regulation of extracellular
      nucleotides released in response to hypoxia and inflammation through E-NTPDase
      and E-ADA enzymes represent an important control of purine-mediated in the SCA
      disease, avoiding elevated adenosine levels in the extracellular medium and
      consequent organ injuries in these patients. The pro-inflammatory cytokines
      decreased levels by use of hydroxyurea occur in attempt to reduce the pro
      inflammatory response and prevent vaso-oclusive crisis. 

PMID- 26211590
TI  - Thrombospondin promoted anti-tumor of adenovirus-mediated calreticulin in breast
      cancer: Relationship with anti-CD47.
AB  - OBJECTIVE: Calreticulin (CRT) protein has multifaceted role in carcinogenesis,
      however its role in breast cancer remains unidentified. In this study, we
      attempted to evaluate the effect of overexpressed CRT on breast cancer cells
      viability and proliferation. METHODS: Levels of mRNA and protein expression for
      CRT and CD47 in cells were determined by Quantitative RT-PCR analysis and Western
      blot, respectively. Cells apoptosis was evaluated using Annexin V-FITC assay with
      flow cytometry. Cell viability was assessed using MTT assay. Cell migration and
      autophagy were also evaluated. RESULTS: In breast cancer cells of MCF-7 and MDA
      MB-231, both CRT and CD47 expression were enhanced, compared with that in normal
      breast cells of MCF-10A. Overexpression of CRT by MCF-7 and MDA-MB-231 cells
      transfected with significantly suppressed cell migration, viability as well as
      promote cell apoptosis while exerted no effected on cell autophagy.
      Interestingly, combining of thrombospondin (TSP) and overexpression of CRT
      significantly induced cell autophagy and inhibited tumor growth in MCF-7 cells
      xenograft. In result of chip assay, we observed that TSP treatment promoted
      interaction of TSP with CRT and CD47. CONCLUSION: TSP promoted anti-tumor of
      adenovirus-mediated CRT via forming complexes with CRT and CD47 in breast cancer.

PMID- 26211591
TI  - Biological evaluation of a novel Herceptin-platinum (II) conjugate for efficient
      and cancer cell specific delivery.
AB  - Platinum-based drugs have been widely used for the treatment of malignant tumors.
      However, their applications are limited by severe side effects for their lack of
      selectivity for cancer cells. The development of antibody drug conjugates (ADCs)
      have provided a platform to reduce drug toxicity and improve drug efficacy. Here
      we describe a nover conjugate comprising of Herceptin (an anti-HER2 antibody) and
      platinum drug via a cathepsin B cleavable dipetide for enhancing drug
      accumulation and HER2-positive cancer cell specific delivery. This conjugate is
      believed to be cleaved by cathepsin B, leading to a 1,6-elimination reaction and
      activation of drug release. Herceptin-Pt(II) is evaluated to have approximately
      loaded with 6.4 moles platinum drugs per mole of antibody. We demonstrate that
      Herceptin-Pt(II) retain high and selective binding affinity for HER2 protein and
      HER2-positive SK-BR-3 cancer cells. The in vitro cytotoxicity tests indicate that
      Herceptin-Pt(II) exhibits much higher cytotoxicity than oxaliplatin against SK-BR
      3 cells. More importantly, Herceptin-Pt(II) shows no obvious inhibition against
      the growth of both MCF-7 and MDA-MB-231 cells, which express lower levels of
      HER2. Furthermore, compared with free oxaliplatin, Herceptin significantly
      improved the cellular uptake of platinum drugs in SK-BR-3 cells. In summary,
      Herceptin-platinum (II) conjugate is a remarkable and potent platform for
      efficient and cancer cell specific delivery. 

PMID- 26211592
TI  - Inhibition of c-Myc by 10058-F4 induces growth arrest and chemosensitivity in
      pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a formidable medical challenge due to
      its malignancies and the absence of effective treatment. c-Myc, as an important
      transcription factor, plays crucial roles in cell cycle progression, apoptosis
      and cellular transformation. The c-Myc inhibitor, 10058-F4, has been reported act
      as a tumor suppressor in several different tumors. In current study, the tumor
      suppressive roles of 10058-F4 was observed in human pancreatic cancer cells in
      vitro as demonstrated by decreased cell viability, cell cycle arrest at the G1/S
      transition and increased caspase3/7 activity. And tumor responses to gemcitabine
      were also significantly enhanced by 10058-F4 in PANC-1 and SW1990 cells. In a
      subcutaneous xenograft model, however, 10058-F4 showed no significant influence
      on pancreatic tumorigenesis. When combined with gemcitabine, tumorigenesis was
      drastically attenuated compared with gemcitabine group or 10058-F4 group; this
      synergistic effect was accompanied with decreased PCNA-positive cells and reduced
      TUNEL-positive cells in the combined treated group. Subsequent studies revealed
      that decreased glycolysis may be involved in the inhibitory effect of 10058-F4 on
      PDAC. Taken together, this study demonstrates the roles of 10058-F4 in PDAC and
      provides evidence that 10058-F4 in combination with gemcitabine showed
      significant clinical benefit over the usage of gemcitabine alone. 

PMID- 26211593
TI  - Effect of VTCN1 on progression and metastasis of ovarian carcinoma in vitro and
      vivo.
AB  - BACKGROUND AND PURPOSES: Through reducing immune response, VTCN1 could promote
      carcinoma indirectly. However, the direct effect of VTCN1 on carcinoma was not
      studied clearly, especially on ovarian carcinoma. In this paper, we verified the
      potential effect and mechanism of VTCN1 on ovarian carcinoma. METHODS: The
      influence of high or low VTCN1 expression on the viability of ovarian cancer was
      detected by CKK-8 and annexin V-PI kit. The orthotopicxenograft tumor model was
      performed to evaluate the effect of VTCN1 on the promotion of tumor in vivo.
      Western blot was used to verify the signaling pathways predicted by
      bioinformatics analysis. RESULTS: Low expression of VTCN1 could inhibit the
      viability and metastasis of ovarian carcinoma directly in vitro and vivo;
      Information analysis demonstrated that cell cycle and JAK2/STAT were involved in
      the regulation of VTCN1. The CDK2/4 and CDC25C expression and phosphorylation of
      JAK2/STAT had a direct relationship with the reduction of VTCN1. CONCLUSIONS:
      VTCN1 could affect the viability and metastasis of ovarian carcinoma by reducing
      the expression of CDK2/4 and CDC25C and phosphorylation of JAK2/STAT. It
      indicated that VTCN1 was a potential target for treating ovarian carcinoma.

PMID- 26211594
TI  - Elevated expression of ECT2 predicts unfavorable prognosis in patients with
      colorectal cancer.
AB  - Epithelial cell transforming sequence 2 (ECT2) is a well-studied guanine
      nucleotide exchange factor for the Rho family GTPase, which has been demonstrated
      as an oncogene in many types of human cancers. However, little is known about the
      prognostic value of ECT2 in colorectal cancer (CRC). In current study, we
      investigated the expression pattern and underlying clinical significance of ECT2
      in CRC. ECT2 expression was detected in 345 CRC specimens by
      immunohistochemistry, and its correlation with clinicopathologic parameters and
      prognosis of CRC patients were analyzed. Data from Oncomine database and real
      time PCR demonstrated that ECT2 expression was elevated in CRC compared with
      normal tissues. Among the clinical parameters analyzed, high expression level of
      ECT2 significantly associated with tumor size (P=0.020), serum CEA levels (P =
      0.000) and TNM stage (P=0.027). Kaplan-Meier survival analysis showed that
      patients with high ECT2 expression had a remarkably shorter overall survival. Cox
      regression analysis revealed that ECT2 expression level was a significant and
      independent prognostic factor for overall survival rate of CRC patients. These
      data suggested that ECT2 is an unfavorable biomarker of prognosis in CRC and that
      ECT2 may be a potential therapeutic candidate for CRC treatment. 

PMID- 26211595
TI  - Serum neural precursor cell-expressed, developmentally down regulated 9 (NEDD9)
      level may have a prognostic role in patients with gastric cancer.
AB  - BACKGROUND: Neural precursor cell-expressed, developmentally down regulated 9
      (NEDD9), a member of Crk-associated substrate (CAS) family, is highly expressed
      in multiple cancer types and involved in cancer cell adhesion, migration and
      invasion. The prognostic value of NEDD9 has been evaluated before and its
      expression is a predictor of poor prognosis in cancer patients. The objective of
      this study was to determine the clinical significance of the serum levels of
      NEDD9 in gastric cancer (GC) patients. PATIENTS AND METHODS: A total of 68
      patients with a pathologically confirmed diagnosis of GC were enrolled into this
      study. Serum NEDD9 concentrations were determined by the solid-phase sandwich
      (ELISA) method. Twenty-eight healthy age- and sex-matched controls were included
      into the analysis. RESULTS: The median age at diagnosis was 60years, range 21 to
      84years. Forty-nine (72%) patients were male and cardia was the most common tumor
      localization (n=37, 77%) in GC patients. The most frequent histologic subtype was
      adenocarcinoma (n=45, 66%). Liver was the most common metastatic site in 32
      patients with metastasis (n=14, 44%). Sixty-one percent of 23 metastatic patients
      who received palliative chemotherapy (CTx) were CTx-responsive. The median follow
      up time was 8months (range 1 to 23months). At the end of the observation period,
      17 patients (25%) experienced disease progression and 28 of the remaining
      patients (41%) died. Median progression-free survival (PFS) and overall survival
      (OS) of the whole group were 4.0+/-0.7months [95% confidence interval (CI)=3
      5months] and 14.6+/-1.2months (95% CI=12-17months), respectively. One-year and 2
      year OS rates were 54.4% (95% CI=41.3-67.5) and 51.2% (95% CI=37.3-65.1),
      respectively. The median serum NEDD9 levels of GC patients were significantly
      higher than controls (1339.51 vs. 1187.91pg/mL, P=0.02). There was no significant
      difference according to known disease-related clinicopathological or laboratory
      parameters (P>0.05). Serum NEDD9 levels had a significant impact on PFS (P=0.04).
      On the other hand, serum NEDD9 levels showed no significantly adverse effect on
      OS (P=0.50). CONCLUSION: Serum NEDD9 level may be a diagnostic marker for GC
      patients. Moreover, our study results showed that it was elevated in GC patients
      and had an unfavorable prognostic effect. However, it has no predictive role on
      CTx response.

PMID- 26211596
TI  - Receptors for advanced glycation end products (RAGE) is associated with
      microvessel density and is a prognostic biomarker for clear cell renal cell
      carcinoma.
AB  - The receptor for advanced glycation end products (RAGE) is involved in a variety
      of biological processes, including tumorigenisis. Previous studies have
      demonstrated that RAGE regulates the neo-angiogenesis related downstream molecule
      - vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we investigated
      the potential relationship between RAGE, VEGFR-2 and angiogenesis in 80 renal
      cell carcinoma (RCC) patients. Real-time quantitative PCR and ELISA analysis were
      used to explore the RAGE and VEGFR-2 gene expression levels and the protein of
      VEGFR-2 expression. Meanwhile, angiogenesis was detected by the semi
      quantification of endothelial cell marker CD34 combined with caldesmon, which was
      detected by microvessel density (MVD) technique and immunohistochemistry. Tumors
      were classified as low or high RAGE-expressing using the median as the cut-off.
      Immunofluorescence staining for RAGE protein was performed as well. Additionally,
      the median gene expression levels of VEGFR-2 in the tumors were significantly
      lower expressing low levels of RAGE expression, 0.34 (95% CI, 0.28-0.39) compared
      to the expressing high levels of RAGE expression, 0.45 (95% CI, 0.29-0.61),
      (P=0.03). The median MVD was significantly lower in the tumors expressing low
      levels of RAGE, 6.5 (95% CI, 6.21-7.43), compared to the expressing high levels,
      7.9 (95% CI, 6.25-8.93), (P<0.01). Further, a positive association was certified
      with VEGFR-2 protein levels, P=0.07. Besides, RCC with high levels of RAGE
      expression are associated with high VEGFR-2 mRNA/protein levels and a higher
      density of microvessels; conversely, Kaplan-Meier survival analysis suggests that
      a significant correlation of elevated RAGE expression with decreased overall
      survival and metastasis-free survival. Our results establish that RAGE was
      identified as a potential prognostic biomarker for disease prognosis of RCC. 

PMID- 26211597
TI  - MicroRNA-708 is downregulated in hepatocellular carcinoma and suppresses tumor
      invasion and migration.
AB  - BACKGROUND: MicroRNA-708 (miR-708) has been identified as one of down-regulated
      miRNAs in hepatocellular carcinoma (HCC) tissues by Taqman miRNAs array and
      confirmed quantitatively by reverse transcription polymerase chain reaction (qRT
      PCR). However, its involvement in HCC remains unclear. The aim of this study was
      to investigate the roles of miR-708 in carcinogenesis and cancer progression of
      HCC. MATERIALS AND METHODS: QRT-PCR was performed to detect the expression of miR
      708 in 100 pairs of HCC and adjacent non cancerous tissues. Then, its
      associations with various clinicopathological features of HCC patients were
      statistically evaluated. After that, we also observed the effects of enforced miR
      708 expression on migration and invasion of HCC cells in vitro. RESULT: Our data
      confirmed that the expression level of miR-708 in HCC tissues was significantly
      lower than those in adjacent non-cancerous tissues (P=0.001). In addition, low
      miR-708 expression was found to be closely correlated with high Edmondson-Steiner
      grading (P=0.02) and advanced Tumor Node Metastasis (TNM) stage (P=0.01).
      Furthermore, the enforced expression of miR-708 could suppress the migration and
      invasion of HCC cell lines in vitro. CONCLUSION: Our findings support that miR
      708, which is frequently down-regulated in HCC, may contribute to the aggressive
      progression of HCC and inhibit HCC cell mobility. Further studies on the
      identification of its target genes are required to be performed.

PMID- 26211598
TI  - Preclinical model for identification of therapeutic targets for CML offers clues
      for handling imatinib resistance.
AB  - Success of imatinib in chronic myeloid leukemia (CML) therapy has undoubtedly
      proved utility of signalling molecules as therapeutic targets. However,
      development of imatinib resistance and progression to blastic crisis are the
      current challenges in clinics. To develop therapeutic alternatives for CML,
      understanding of signalling events downstream of bcr-abl might be helpful.
      Current CML cell lines do not give comprehensive picture of signalling events
      involved in pathogenesis of CML. Hence, there is a major unmet need for a better
      preclinical model for CML. Here, we report on development of RIN9815/bcr-abl, a
      novel cell line model that mimics signalling events in CML PMNL. Studies on
      crucial signalling molecules i.e., ras, rac, rhoA and actin in this cell line
      identified rhoA as the key regulator involved in CML cell function as well as
      proliferation of both, imatinib sensitive and resistant cells. Hence, RIN9815/bcr
      abl could serve as the unique preclinical model in understanding pathogenesis of
      CML and in drug development. 

PMID- 26211599
TI  - Gall-forming root-knot nematodes hijack key plant cellular functions to induce
      multinucleate and hypertrophied feeding cells.
AB  - Among plant-parasitic nematodes, the root-knot nematodes (RKNs) of the
      Meloidogyne spp. are the most economically important genus. RKN are root
      parasitic worms able to infect nearly all crop species and have a wide geographic
      distribution. During infection, RKNs establish and maintain an intimate
      relationship with the host plant. This includes the creation of a specialized
      nutritional structure composed of multinucleate and hypertrophied giant cells,
      which result from the redifferentiation of vascular root cells. Giant cells
      constitute the sole source of nutrients for the nematode and are essential for
      growth and reproduction. Hyperplasia of surrounding root cells leads to the
      formation of the gall or root-knot, an easily recognized symptom of plant
      infection by RKNs. Secreted effectors produced in nematode salivary glands and
      injected into plant cells through a specialized feeding structure called the
      stylet play a critical role in the formation of giant cells. Here, we describe
      the complex interactions between RKNs and their host plants. We highlight
      progress in understanding host plant responses, focusing on how RKNs manipulate
      key plant processes and functions, including cell cycle, defence, hormones,
      cellular scaffold, metabolism and transport. 

PMID- 26211601
TI  - Novel NOG mutation in Japanese patients with stapes ankylosis with broad thumbs
      and toes.
AB  - Human noggin (NOG) gene mutation causes multiple bony disorders showing up as
      stapes ankylosis with broad thumbs and toes (SABTT), proximal symphalangism
      (SYM1), multiple synostoses syndrome 1 (SYNS1), tarsal-carpal coalition syndrome
      (TCC) and brachydactyly type B2 (BDB2). These phenotypes are defined as NOG
      related syndromes with the same mutation. Some of these syndromes feature stapes
      ankylosis as one of the several bony symptoms. Here, we report a Japanese family
      with conductive hearing loss due to congenital stapes ankylosis. This family
      showed multiple features and was diagnosed with SABTT. We performed analysis of
      the NOG in the family by direct sequence analysis, and found a novel NOG
      mutation: c.682 T> G (p.C228G). Our results and a review of previous cases with
      NOG protein conformation suggest that this mutated NOG protein lead to a change
      in antagonist activity in BMPs and/or a haploinsufficiency that likely impaired
      finger 2 structure. 

PMID- 26211602
TI  - Controversies in small cell carcinoma of the head and neck: Prophylactic cranial
      irradiation (PCI) after primary complete initial remission.
AB  - Small cell carcinoma of head and neck region (SmCCHN) represents a rare entity
      and its management remains a significant clinical challenge. Complete initial
      response to primary therapy poses a difficult and controversial scenario for
      radiation oncologists. Prophylactic cranial irradiation (PCI) has long been
      established in the management of small cell lung cancer; however, its role in
      SmCCHN is still called into question. The rationale behind PCI lies in the
      eradication of possible micro-metastatic brain disease, which is often documented
      in this type of cancer. No randomized trials on this topic are available. This
      review, based on 20 retrospective studies, addresses the controversies in the use
      of PCI in SmCCHN management. 

PMID- 26211600
TI  - In Support of a Patient-Driven Initiative and Petition to Lower the High Price of
      Cancer Drugs.

PMID- 26211604
TI  - Optical coherence tomography detects structural abnormalities of the nasal mucosa
      in patients with cystic fibrosis.
AB  - BACKGROUND: Chronic inflammation and remodeling of the airways remain a hallmark
      of cystic fibrosis (CF). However, knowledge of the associated mucosal micro
      anatomical changes is limited. We evaluated the potential of optical coherence
      tomography (OCT) for in vivo imaging of the upper airway mucosa in CF patients.
      METHODS: A flexible OCT probe was used for cross-sectional imaging of the nasal
      mucosa in 25 CF patients and 25 healthy controls. RESULTS: OCT images showed
      mucosal details including epithelium, basement membrane, lamina propria with
      seromucinous glands, and underlying cartilaginous structures. Mean nasal mucosa
      and epithelial layer thickness were increased in CF compared to controls. In CF
      patients, antibiotic therapy was associated with reduced nasal mucosa thickening.
      CONCLUSIONS: OCT detected mucosal changes associated with upper airway
      inflammation and response to antibiotic therapy in CF patients. OCT may be a
      useful tool for quantitative in vivo assessment of structural changes of the
      airway mucosa.

PMID- 26211605
TI  - A randomized controlled trial of vitamin D replacement strategies in pediatric CF
      patients.
AB  - BACKGROUND: Vitamin D insufficiency is common in children with cystic fibrosis
      (CF), yet data are sparse regarding the most effective form of vitamin D
      supplementation. The aim of this study was to compare two different vitamin D
      replacement regimens. METHODS: We conducted a randomized controlled trial
      comparing 50,000 IU of ergocalciferol (vitamin D2) twice weekly for 8 weeks
      versus 50,000 IU of cholecalciferol (vitamin D3) weekly in patients with CF,
      pancreatic insufficiency, age 6-21 years and a 25(OH)D<30 ng/mL. The primary
      outcome was change in serum 25(OH)D concentration. For secondary analyses, we
      examined changes in IgG, IgE and CRP in patients who normalized their vitamin D
      levels. RESULTS: A total of 47 patients completed the trial. The mean pre
      treatment 25(OH)D concentration was 23.1 (SD 4.7) ng/mL. The overall mean
      increase in 25(OH)D was 11.1 (11.9) ng/mL and 31/47 (66%) achieved a 25(OH)D
      concentration >= 30 ng/mL; of the 26 participants who received D2, 18 (69%)
      achieved sufficiency while 13/21 (62%) participants treated with D3 achieved
      sufficiency. There was no difference between groups in change of 25(OH)D
      (p=0.65). Similarly, there was no difference in the number of patients to achieve
      vitamin D sufficiency between treatments (p=0.6). CONCLUSIONS: Ergocalciferol
      administered as 50,000 IU twice weekly is as effective as cholecalciferol 50,000
      IU weekly for 8 weeks in pediatric patients with CF and vitamin D insufficiency.
      Only 66% of the patients studied achieved the desired 25(OH)D concentration.

PMID- 26211606
TI  - Chlamydia trachomatis infection in young adults - association with concurrent
      partnerships and short gap length between partners.
AB  - BACKGROUND: Sexually transmitted infections (STIs) continue to be highly
      prevalent in young people. New understanding of sexual risk behaviour is
      essential for future preventive initiatives. Studies based on self-reported STI
      history indicate that gap length between sexual partnerships is an important
      determinant in STI transmission, but little is known about the impact of
      concurrent partnerships and short gap length. This study aimed to examine the
      significance of concurrent partnerships and short gap length between serially
      monogamous partnerships in Chlamydia trachomatis-infected individuals compared to
      the general population. METHODS: A Danish cross-sectional study was conducted
      among individuals aged 15-29 years with a verified C. trachomatis infection and a
      sample of the background population. Participants answered a web-based
      questionnaire on sexual behaviour. Associations were identified in multivariate
      analyses. RESULTS: In total, 36% of the included young adults reported that they
      had two or more partners within the last year. Concurrent partnerships were
      frequent (46%), and the gap length between serially monogamous partnerships
      tended to be short (median gap length, 64 days, interquartile interval (IQI) =
      31, 122). A strong association was found between concurrent partnerships (odds
      ratio (OR) = 12.5, 95% confidence interval (CI) = 7.7-20.4), short gap length
      between serially monogamous partnerships (OR = 10.0, 95% CI = 5.7-17.4) and
      having a verified C. trachomatis infection. CONCLUSIONS: C. trachomatis infection
      was strongly associated with concurrent partnerships or short gap length between
      serially monogamous partnerships. These findings have considerable implications
      for public health policy. Both types of risk factors should be considered in
      future preventive interventions aiming to reduce the spread of C. trachomatis
      infections.

PMID- 26211607
TI  - A detailed quantitative outcome measure of glycosaminoglycans in human articular
      cartilage for cell therapy and tissue engineering strategies.
AB  - OBJECTIVE: Ideally, cartilage regenerative cell therapy should produce a tissue
      which closely matches the microstructure of native cartilage. Benchmark reference
      information is necessary to assess the quality of engineered cartilage. Our goal
      was to examine the variation in glycosaminoglycans (GAGs) in cartilage zones
      within human knee joints of different ages. DESIGN: Osteochondral biopsies were
      removed from the medial femoral condyles of deceased persons aged 20-50 years.
      Fluorophore-Assisted Carbohydrate Electrophoresis (FACE) was used to profile GAGs
      through the superficial, middle and deep zones of the articular cartilage.
      Differences were identified by statistical analysis. RESULTS: Cartilage from the
      younger biopsies had 4-fold more hyaluronan in the middle zone than cartilage
      from the older biopsies. The proportion of hyaluronan decreased with increasing
      age. Cartilage from the middle and deep zones of younger biopsies had
      significantly more chondroitin sulphate and keratan sulphate than the cartilage
      from older biopsies. This would suggest that chondrocytes synthesise more
      sulphated GAGs when deeper in the tissue and therefore in conditions of hypoxia.
      With increasing age, there was significantly more chondroitin-6 sulphate than
      chondroitin-4 sulphate. For the first time, unsulphated chondroitin was detected
      in the superficial zone. CONCLUSIONS: As an outcome measure, FACE offers the
      potential of a complete, detailed assessment of all GAGs and offers more
      information that the widely used 1,9-dimethylmethylene blue (DMMB) dye assay.
      FACE could be very useful in the evolving cartilage regeneration field.

PMID- 26211609
TI  - Structural Basis of Proline-Proline Peptide Bond Specificity of the
      Metalloprotease Zmp1 Implicated in Motility of Clostridium difficile.
AB  - Clostridium difficile is a pathogenic bacterium causing gastrointestinal diseases
      from mild diarrhea to toxic megacolon. In common with other pathogenic bacteria,
      C. difficile secretes proteins involved in adhesion, colonization, and
      dissemination. The recently identified Zmp1 is an extracellular metalloprotease
      showing a unique specificity for Pro-Pro peptide bonds. The endogenous substrates
      of Zmp1 are two surface proteins implicated in adhesion of C. difficile to
      surface proteins of human cells. Thus, Zmp1 is believed to be involved in the
      regulation of the adhesion-motility balance of C. difficile. Here, we report
      crystal structures of Zmp1 from C. difficile in its unbound and peptide-bound
      forms. The structure analysis revealed a fold similar to Bacillus anthracis
      lethal factor. Crystal structures in the open and closed conformation of the S
      loop shed light on the mode of binding of the substrate, and reveal important
      residues for substrate recognition and the strict specificity of Zmp1 for Pro-Pro
      peptide bonds. 

PMID- 26211608
TI  - Charge based intra-cartilage delivery of single dose dexamethasone using Avidin
      nano-carriers suppresses cytokine-induced catabolism long term.
AB  - OBJECTIVE: Avidin exhibits ideal characteristics for targeted intra-cartilage
      drug delivery: its small size and optimal positive charge enable rapid
      penetration through full-thickness cartilage and electrostatic binding
      interactions that give long half-lives in vivo. Here we conjugated Avidin with
      dexamethasone (DEX) and tested the hypothesis that single-dose Avidin-delivered
      DEX can ameliorate catabolic effects in cytokine-challenged cartilage relevant to
      post-traumatic OA. METHODS: Avidin was covalently conjugated with DEX using fast
      (ester) and slow, pH-sensitive release (hydrazone) linkers. DEX release kinetics
      from these conjugates was characterized using (3)H-DEX-Avidin (scintillation
      counting). Cartilage explants treated with IL-1alpha were cultured with or
      without Avidin-DEX conjugates and compared to soluble DEX. Sulfated
      glycosaminoglycan (sGAG) loss and biosynthesis rates were measured using DMMB
      assay and (35)S-incorporation, respectively. Chondrocyte viability was measured
      using fluorescence staining. RESULTS: Ester linker released DEX from Avidin
      significantly faster than hydrazone under physiological buffer conditions. Single
      dose Avidin-DEX suppressed cytokine-induced sGAG loss over 3-weeks, rescued IL
      1alpha-induced cell death, and restored sGAG synthesis levels without causing
      cytotoxicity. The two Avidin-DEX conjugates in 1:1 combination (fast:slow) had
      the most prominent bioactivity compared to single dose soluble-DEX, which had a
      shorter-lived effect and thus needed continuous replenishment throughout the
      culture period to ameliorate catabolic effects. CONCLUSION: Intra-cartilage drug
      delivery remains inadequate as drugs rapidly clear from the joint, requiring
      multiple injections or sustained release of high doses in synovial fluid. A
      single dose of Avidin-conjugated drug enables rapid uptake and sustained delivery
      inside cartilage at low intratissue doses, and potentially can minimize unwanted
      drug exposure to other joint tissues.

PMID- 26211610
TI  - Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein
      with Unique Features.
AB  - Eukaryotic initiation factor 2 (eIF2), a heterotrimeric guanosine triphosphatase,
      has a central role in protein biosynthesis by supplying methionylated initiator
      tRNA to the ribosomal translation initiation complex and by serving as a target
      for translational control in response to stress. Recent work identified a novel
      step indispensable for eIF2 function: assembly of eIF2 from its three subunits by
      the cell proliferation protein Cdc123. We report the first crystal structure of a
      Cdc123 representative, that from Schizosaccharomyces pombe, both isolated and
      bound to domain III of Saccharomyces cerevisiae eIF2gamma. The structures show
      that Cdc123 resembles enzymes of the ATP-grasp family. Indeed, Cdc123 binds ATP
      Mg(2+), and conserved residues contacting ATP-Mg(2+) are essential for Cdc123 to
      support eIF2 assembly and cell viability. A docking of eIF2alphagamma onto
      Cdc123, combined with genetic and biochemical experiments, allows us to propose a
      model explaining how Cdc123 participates in the biogenesis of eIF2 through
      facilitating assembly of eIF2gamma to eIF2alpha. 

PMID- 26211611
TI  - alpha- and beta-Tubulin Lattice of the Axonemal Microtubule Doublet and Binding
      Proteins Revealed by Single Particle Cryo-Electron Microscopy and Tomography.
AB  - Microtubule doublet (MTD) is the main skeleton of cilia/flagella. Many proteins,
      such as dyneins and radial spokes, bind to MTD, and generate or regulate force.
      While the structure of the reconstituted microtubule has been solved at atomic
      resolution, nature of the axonemal MTD is still unclear. There are a few
      hypotheses of the lattice arrangement of its alpha- and beta-tubulins, but it has
      not been described how dyneins and radial spokes bind to MTD. In this study, we
      analyzed the three-dimensional structure of Tetrahymena MTD at ~19 A resolution
      by single particle cryo-electron microscopy. To identify alpha- and beta
      tubulins, we combined image analysis of MTD with specific kinesin decoration.
      This work reveals that alpha- and beta-tubulins form a B-lattice arrangement in
      the entire MTD with a seam at the outer junction. We revealed the unique way in
      which inner arm dyneins, radial spokes, and proteins inside MTD bind and bridge
      protofilaments.

PMID- 26211612
TI  - The Closing Mechanism of DNA Polymerase I at Atomic Resolution.
AB  - DNA polymerases must quickly and accurately distinguish between similar nucleic
      acids to form Watson-Crick base pairs and avoid DNA replication errors.
      Deoxynucleoside triphosphate (dNTP) binding to the DNA polymerase active site
      induces a large conformational change that is difficult to characterize
      experimentally on an atomic level. Here, we report an X-ray crystal structure of
      DNA polymerase I bound to DNA in the open conformation with a dNTP present in the
      active site. We use this structure to computationally simulate the open to closed
      transition of DNA polymerase in the presence of a Watson-Crick base pair. Our
      microsecond simulations allowed us to characterize the key steps involved in
      active site assembly, and propose the sequence of events involved in the
      prechemistry steps of DNA polymerase catalysis. They also reveal new features of
      the polymerase mechanism, such as a conserved histidine as a potential proton
      acceptor from the primer 3'-hydroxyl. 

PMID- 26211613
TI  - The Structural Role of Antibody N-Glycosylation in Receptor Interactions.
AB  - Asparagine(N)297-linked glycosylation of immunoglobulin G (IgG) Fc is required
      for binding to FcgammaRIIa, IIb, and IIIa, although it is unclear how it
      contributes. We found the quaternary structure of glycosylated Fc was
      indistinguishable from aglycosylated Fc, indicating that N-glycosylation does not
      maintain relative Fc Cgamma2/Cgamma3 domain orientation. However, the
      conformation of the C'E loop, which contains N297, was significantly perturbed in
      the aglycosylated Fc variant. The conformation of the C'E loop as measured with a
      range of Fc variants shows a strong correlation with FcgammaRIIIa affinity. These
      results indicate that the primary role of the IgG1 Fc N-glycan is to stabilize
      the C'E loop through intramolecular interactions between carbohydrate and amino
      acid residues, and preorganize the FcgammaRIIIa interface for optimal binding
      affinity. The features that contribute to the capacity of the IgG1 Fc N-glycan to
      restrict protein conformation and tune binding affinity are conserved in other
      antibodies including IgG2-IgG4, IgD, IgE, and IgM. 

PMID- 26211614
TI  - Relative contributions of mercury bioavailability and microbial growth rate on
      net methylmercury production by anaerobic mixed cultures.
AB  - Monomethylmercury (MeHg) is produced in many aquatic environments by anaerobic
      microorganisms that take up and methylate inorganic forms of Hg(II). Net
      methylation of Hg(II) appears to be correlated with factors that affect the
      activity of the anaerobic microbial community and factors that increase the
      bioavailability of Hg(II) to these organisms. However, the relative importance of
      one versus the other is difficult to elucidate even though this information can
      greatly assist remediation efforts and risk assessments. Here, we investigated
      the effects of Hg speciation (dissolved Hg and nanoparticulate HgS) and microbial
      activity on the net production of MeHg using two mixed microbial cultures that
      were enriched from marine sediments under sulfate reducing conditions. The
      cultures were amended with dissolved Hg (added as a dissolved nitrate salt) and
      nanoparticulate HgS, and grown under different carbon substrate concentrations.
      The results indicated that net mercury methylation was the highest for cultures
      incubated in the greatest carbon substrate concentration (60 mM) compared to
      incubations with less carbon (0.6 and 6 mM), regardless of the form of mercury
      amended. Net MeHg production in cultures exposed to HgS nanoparticles was
      significantly slower than in cultures exposed to dissolved Hg; however, the
      difference diminished with slower growing cultures with low carbon addition (0.6
      mM). The net Hg methylation rate was found to correlate with sulfate reduction
      rate in cultures exposed to dissolved Hg, while methylation rate was roughly
      constant for cultures exposed to nanoparticulate HgS. These results indicated a
      potential threshold of microbial productivity: below this point net MeHg
      production was limited by microbial activity, regardless of Hg bioavailability.
      Above this threshold of productivity, Hg speciation became a contributing factor
      towards net MeHg production.

PMID- 26211615
TI  - Isoform-specific interactions of the von Hippel-Lindau tumor suppressor protein.
AB  - Deregulation of the von Hippel-Lindau tumor suppressor protein (pVHL) is
      considered one of the main causes for malignant renal clear-cell carcinoma
      (ccRCC) insurgence. In human, pVHL exists in two isoforms, pVHL19 and pVHL30
      respectively, displaying comparable tumor suppressor abilities. Mutations of the
      p53 tumor suppressor gene have been also correlated with ccRCC insurgence and
      ineffectiveness of treatment. A recent proteomic analysis linked full length
      pVHL30 with p53 pathway regulation through complex formation with the p14ARF
      oncosuppressor. The alternatively spliced pVHL19, missing the first 53 residues,
      lacks this interaction and suggests an asymmetric function of the two pVHL
      isoforms. Here, we present an integrative bioinformatics and experimental
      characterization of the pVHL oncosuppressor isoforms. Predictions of the pVHL30 N
      terminus three-dimensional structure suggest that it may exist as an ensemble of
      structured and disordered forms. The results were used to guide Yeast two hybrid
      experiments to highlight isoform-specific binding properties. We observed that
      the physical pVHL/p14ARF interaction is specifically mediated by the 53 residue
      long pVHL30 N-terminal region, suggesting that this N-terminus acts as a further
      pVHL interaction interface. Of note, we also observed that the shorter pVHL19
      isoform shows an unexpected high tendency to form homodimers, suggesting an
      additional isoform-specific binding specialization. 

PMID- 26211617
TI  - Geologic controls on supercritical geothermal resources above magmatic
      intrusions.
AB  - A new and economically attractive type of geothermal resource was recently
      discovered in the Krafla volcanic system, Iceland, consisting of supercritical
      water at 450  degrees C immediately above a 2-km deep magma body. Although
      utilizing such supercritical resources could multiply power production from
      geothermal wells, the abundance, location and size of similar resources are
      undefined. Here we present the first numerical simulations of supercritical
      geothermal resource formation, showing that they are an integral part of magma
      driven geothermal systems. Potentially exploitable resources form in rocks with a
      brittle-ductile transition temperature higher than 450  degrees C, such as
      basalt. Water temperatures and enthalpies can exceed 400  degrees C and 3 MJ kg(
      1), depending on host rock permeability. Conventional high-enthalpy resources
      result from mixing of ascending supercritical and cooler surrounding water. Our
      models reproduce the measured thermal conditions of the resource discovered at
      Krafla. Similar resources may be widespread below conventional high-enthalpy
      geothermal systems. 

PMID- 26211616
TI  - Volatiles, color characteristics and other physico-chemical parameters of
      commercial Moroccan honeys.
AB  - Seven commercial Moroccan honeys were considered for chemical characterisation.
      Volatile fraction, total polyphenols content, antioxidant and antiradical
      activities were evaluated by employing different analytical methodologies.
      Several physical parameters such as refractive index, pH, water content, solids
      content and colour were measured. Volatile fraction revealed an abundant presence
      of cis- and trans-linalool oxide in the seven studied samples. The presence of
      high levels of compounds related to the Maillard reaction, like furfural and
      hydroxymethylfurfural, could be the result of thermal treatments used to liquefy
      commercial honeys or of long storage times. The CIE L*a*b*C*(ab)h degrees (ab)
      chromatic coordinates confirmed the advanced stage of the Maillard reaction,
      showing L* values lower than the common values found for honey of similar
      typologies.

PMID- 26211618
TI  - Rice stripe virus counters reduced fecundity in its insect vector by modifying
      insect physiology, primary endosymbionts and feeding behavior.
AB  - Virus-vector relationships can be complex and diverse as a result of long-term
      coevolution. Understanding these interactions is crucial for disease and vector
      management. Rice stripe virus (RSV) is known to be transovarially transmitted
      within its vector, Laodelphax striatellus, and causes serious rice stripe
      disease. In RSV-infected L. striatellus, we found contrasting changes in vector
      fecundity, physiology, primary endosymbionts (i.e. yeast-like symbionts, YLS) and
      feeding behavior that can interact to affect the spread of RSV. RSV-infected L.
      striatellus exhibited a significant decrease in fecundity that could lead a
      reduction of viruliferous individuals in populations. As a potential response to
      this loss, RSV infection also significantly shortened nymphal stage duration,
      which can strengthen RSV vertical circulation in L. striatellus populations and
      promote RSV spreading by adult migration and dispersal. Down-regulated JHAMT and
      up-regulated CYP307A1 in the juvenile hormone and ecdysteroid pathways,
      respectively, were linked to accelerated development. RSV-infected adults were
      also found to have higher body weight in conjunction with increased YLS
      abundance. Furthermore, prolonged host plant phloem exposure to salivation by RSV
      infected adults should further enhance RSV horizontal transmission. Our study
      highlights potential strategies of RSV in enhancing its transmission, and
      provides new insights into the complexity of virus-vector interactions. 

PMID- 26211619
TI  - Age and gender differences in kinematics of powerful instep kicks in soccer.
AB  - Soccer kicking training should be adjusted to the characteristics of the
      athletes. Therefore, examination of differences in kicking kinematics of females
      and pubertal players relative to males is worthwhile. The purpose of the study
      was to compare kicking kinematics and segmental sequence parameters between male,
      female, and pubertal players. Ten adult male, ten adult female, and ten male
      pubertal players participated in the study. Participants performed five
      consecutive kicking trials of a stationary ball, as powerful as they could.
      Analysis of variance showed significantly higher ball velocity, higher joint
      linear velocities for the knee and the hip, and higher angular velocities of the
      knee and the ankle for males compared to female and pubertal players (p < 0.05).
      Similarly, the peak joint velocity was achieved significantly closer to ball
      impact in males compared to other groups (p < 0.05). Males also showed a more
      plantarflexed ankle immediately before ball impact (p < 0.05). Females and
      pubertal players may benefit from skill training aiming to increase ankle
      plantarflexion and hip flexion prior to ball impact, and to adjust thigh and
      shank motion, such that the shank-foot segment travels through a higher range of
      motion and with a greater velocity.

PMID- 26211620
TI  - Evidence for smaller right amygdala volumes in posttraumatic stress disorder
      following childhood trauma.
AB  - Hippocampus and amygdala volumes in posttraumatic stress disorder (PTSD) related
      to childhood trauma are relatively understudied, albeit the potential importance
      to the disorder. Whereas some studies reported smaller hippocampal volumes,
      little evidence was found for abnormal amygdala volumes. Here we investigated
      hippocampus and amygdala volumes and shapes in an adult sample of PTSD patients
      related to childhood trauma. T1-weighted MR images were acquired from 12 female
      PTSD patients with trauma related to physical, sexual, and/or emotional abuse
      before age 18, and from 12 matched controls. Hippocampus and amygdala were
      segmented, and volumes were calculated and corrected for the total intracranial
      volume. Additionally, a shape analysis was done on the surface of the structures
      to explore abnormalities in specific subnuclei. Smaller right amygdala volumes
      were found in PTSD patients as compared with the controls. This difference
      appeared to be located specifically in the basolateral and superficial nuclei
      groups. Severity of sexual abuse during childhood was negatively correlated with
      the size of the amygdala. No difference in hippocampal volumes was found.
      Although our results are not conclusive, traumatic events in childhood might
      impede normal development of the amygdala, which could render a person more
      vulnerable to develop PTSD later in life. 

PMID- 26211621
TI  - Investigation of white matter abnormalities in first episode psychosis patients
      with persistent negative symptoms.
AB  - Aberrant white matter structures in fronto-temporal regions have previously been
      identified in patients with schizophrenia. However, scant research has focused on
      white matter integrity in patients presenting with a first episode of psychosis
      (FEP) with persistent negative symptoms (PNS). This study aimed to explore
      microstructure in the neurocircuitry proposed to be involved in PNS, by using a
      region-of-interest approach. Secondly, the relationship between individual
      negative symptoms and white matter were explored. Fractional anisotropy (FA) was
      measured in the fornix and three other tracts bilaterally including the uncinate
      fasciculus, superior longitudinal fasciculus and the cingulum bundle. Twelve
      patients with PNS were compared to a non-PNS group (52) and a healthy control
      group (51). Results showed that the PNS group had significantly lower FA values
      in the fornix when compared to healthy controls and that the non-PNS group had
      significantly lower FA values in the right uncinate fasciculus compared to
      healthy controls. Significant correlations were observed between SANS global
      score for anhedonia-asociality and lower FA values in the right cingulum bundle.
      Our results suggest that fronto-temporal white matter might be more closely
      related to PNS and that this relationship may possibly be mediated by greater
      anhedonia in PNS patients. 

PMID- 26211622
TI  - Comparison of automated brain segmentation using a brain phantom and patients
      with early Alzheimer's dementia or mild cognitive impairment.
AB  - Magnetic resonance imaging (MRI) and brain volumetry allow for the quantification
      of changes in brain volume using automatic algorithms which are widely used in
      both, clinical and scientific studies. However, studies comparing the reliability
      of these programmes are scarce and mainly involved MRI derived from younger
      healthy controls. This study evaluates the reliability of frequently used
      segmentation programmes (SPM, FreeSurfer, FSL) using a realistic digital brain
      phantom and MRI brain acquisitions from patients with manifest Alzheimer's
      disease (AD, n=34), mild cognitive impairment (MCI, n=60), and healthy subjects
      (n=32) matched for age and sex. Analysis of the brain phantom dataset
      demonstrated that SPM, FSL and FreeSurfer underestimate grey matter and
      overestimate white matter volumes with increasing noise. FreeSurfer calculated
      overall smaller brain volumes with increasing noise. Image inhomogeneity had only
      minor, non- significant effects on the results obtained with SPM and FreeSurfer
      5.1, but had effects on the FSL results (increased white matter volumes with
      decreased grey matter volumes). The analysis of the patient data yielded
      decreasing volumes of grey and white matter with progression of brain atrophy
      independent of the method used. FreeSurfer calculated the largest grey matter and
      the smallest white matter volumes. FSL calculated the smallest grey matter
      volumes; SPM the largest white matter volumes. Best results are obtained with
      good image quality. With poor image quality, especially noise, SPM provides the
      best segmentation results. An optimised template for segmentation had no
      significant effect on segmentation results. While our findings underline the
      applicability of the programmes investigated, SPM may be the programme of choice
      when MRIs with limited image quality or brain images of elderly should be
      analysed. 

PMID- 26211623
TI  - Temporal profile of brain response to alprazolam in patients with generalized
      anxiety disorder.
AB  - This study investigated the temporal pattern of brain response to emotional
      stimuli during 28 days of alprazolam treatment among patients with generalized
      anxiety disorder (GAD) randomized 2:1 to drug or placebo in a double-blind
      design. Functional magnetic resonance imaging scans obtained during an emotion
      face matching task (EFMT) and an affective stimulus expectancy task (STIMEX) were
      performed at baseline, one hour after initial drug administration and 28 days
      later. Alprazolam significantly reduced scores on the Hamilton Anxiety Scale and
      the Penn State Worry Questionnaire after one week and 28 days of treatment. Brain
      activation in the amygdala during the EFMT and in the insula during the STIMEX
      was reduced one hour after alprazolam administration but returned to baseline
      levels at Day 28. Exploratory analyses revealed significant treatment differences
      in brain activity during the STIMEX on Day 28 in frontal lobe, caudate nucleus,
      middle temporal gyrus, secondary visual cortex, and supramarginal gyrus. These
      results are consistent with the notion that the neural mechanisms supporting
      sustained treatment effects of benzodiazepines in GAD differ from those
      underlying their acute effects. 

PMID- 26211624
TI  - Health equity and access to health facility delivery and Caesarean sections in
      Morocco.

PMID- 26211625
TI  - Polarization-tuned Dynamic Color Filters Incorporating a Dielectric-loaded
      Aluminum Nanowire Array.
AB  - Nanostructured spectral filters enabling dynamic color-tuning are saliently
      attractive for implementing ultra-compact color displays and imaging devices.
      Realization of polarization-induced dynamic color-tuning via one-dimensional
      periodic nanostructures is highly challenging due to the absence of plasmonic
      resonances for transverse-electric polarization. Here we demonstrate highly
      efficient dynamic subtractive color filters incorporating a dielectric-loaded
      aluminum nanowire array, providing a continuum of customized color according to
      the incident polarization. Dynamic color filtering was realized relying on
      selective suppression in transmission spectra via plasmonic resonance at a metal
      dielectric interface and guided-mode resonance for a metal-clad dielectric
      waveguide, each occurring at their characteristic wavelengths for transverse
      magnetic and electric polarizations, respectively. A broad palette of colors,
      including cyan, magenta, and yellow, has been attained with high transmission
      beyond 80%, by tailoring the period of the nanowire array and the incident
      polarization. Thanks to low cost, high durability, and mass producibility of the
      aluminum adopted for the proposed devices, they are anticipated to be diversely
      applied to color displays, holographic imaging, information encoding, and anti
      counterfeiting. 

PMID- 26211627
TI  - Identifying novel mycobacterial stress associated genes using a random
      mutagenesis screen in Mycobacterium smegmatis.
AB  - Cell envelope associated components of Mycobacterium tuberculosis (M.tb) have
      been implicated in stress response, immune modulation and in vivo survival of the
      pathogen. Although many such factors have been identified, there is a large
      disparity between the number of genes predicted to be involved in functions
      linked to the envelope and those described in the literature. To identify and
      characterise novel stress related factors associated with the mycobacterial cell
      envelope, we isolated colony morphotype mutants of Mycobacterium smegmatis (M.
      smegmatis), based on the hypothesis that mutants with unusual colony morphology
      may have defects in the biosynthesis of cell envelope components. On testing
      their susceptibility to stress conditions relevant to M.tb physiology, multiple
      mutants were found to be sensitive to Isoniazid, Diamide and H2O2, indicative of
      altered permeability due to changes in cell envelope composition. Two mutants
      showed defects in biofilm formation implying possible roles for the target genes
      in antibiotic tolerance and/or virulence. These assays identified novel stress
      associated roles for several mycobacterial genes including sahH, tatB and aceE.
      Complementation analysis of selected mutants with the M. smegmatis genes and
      their M.tb homologues showed phenotypic restoration, validating their link to the
      observed phenotypes. A mutant carrying an insertion in fhaA encoding a forkhead
      associated domain containing protein, showed reduced survival in THP-1
      macrophages, providing in vivo validation to this screen. Taken together, these
      results suggest that the M.tb homologues of a majority of the identified genes
      may play significant roles in the pathogenesis of tuberculosis. 

PMID- 26211626
TI  - The FHL2 regulation in the transcriptional circuitry of human cancers.
AB  - The Four-and-a-half LIM (FHL)-only protein is a subfamily of protein members
      under the LIM-only protein family. These proteins are identified by their
      characteristic four and a half cysteinerich LIM homeodomain. Five members have
      been categorized into the FHL subfamily, which are FHL1, FHL2, FHL3, FHL4 and
      activator of CREM in testis (ACT) in human. FHL2 is amongst the most examined
      members within the family. Fhl2, the gene that code for the protein, is
      transcriptionally regulated by diverse types of transcription factors, for
      example, p53, serum response factor (SRF), and specificity protein 1 (Sp1). The
      expression of FHL2 is found in different tissues and organs and has been reported
      as a critical participant influencing the wide types of cancer such as breast
      cancer, gastrointestinal (GI) cancers, liver cancer and prostate cancer. The
      expression profile of FHL2 appeared to have a significant functional role in the
      carcinogenesis of these cancers which are mediated by different types of
      transcription factor including both tumor suppressors and inducers. In this
      review, we will first describe the molecular network governing FHL2 expression,
      which focus on the transcription factors conveying FHL2-initiated responses. In
      the second part, FHL2-linked cancers and the underlying molecular machinery will
      be discussed. Factors other than transcriptional regulation which may involve the
      cancer progression such as mutations of fhl2 and posttranslational modifications
      of the protein will also be mentioned. 

PMID- 26211628
TI  - Circulating microRNAs in obese and lean heart failure patients: A case-control
      study with computational target prediction analysis.
AB  - AIMS: MicroRNAs (miRs) regulate processes involved in both cardiac remodeling and
      obesity. We investigated if the expression of selected miRs in patients with
      heart failure (HF) is influenced by the presence of obesity. METHODS: In this
      case-control study, we compared plasma levels of miR-21, -130b, -221, -423-5p,
      and the -221/-130b ratio in 57 age- and gender-matched subjects: 40 HF patients
      (20 obese HF and 20 lean HF) and 17 lean healthy controls. Body composition was
      estimated by bioelectrical impedance analysis. MiRs were measured by quantitative
      reverse transcription-PCR. Bioinformatics analysis was performed based on miRs
      findings to predict their putative targets and investigate their biological
      function. RESULTS: HF was associated with increased miR-423-5p levels in both
      lean and obese patients (P<0.05 vs. controls) without differences between HF
      groups. MiR-130b levels were reduced in obese HF patients compared with HF lean
      (P=0.036) and controls (P=0.025). MiR-221 levels were non-significantly increased
      in obese HF patients. MiR-21 levels were not different among the groups. MiR-221/
      130b ratio was increased in obese HF patients, and was positively associated with
      body fat percentage (r=0.43; P=0.002), body mass index (r=0.44; P=0.002), and
      waist circumference (r=0.40; P=0.020). Computational prediction of target genes
      followed by functional enrichment analysis indicated a relevant role of miR-130b
      and miR-221 in modulating the expression of genes associated to cardiovascular
      and endocrine diseases, and suggested their influence in important signaling
      mechanisms and in numerous processes related to the circulatory and endocrine
      systems. CONCLUSIONS: In HF patients, the presence of obesity is associated with
      a differential expression of selected miRs and the miR-221/-130b ratio had
      significant correlations with adiposity parameters. Computational target
      prediction analysis identified several interrelated pathways targeted by miR-130b
      and miR-221 with a known relationship with endocrine and cardiovascular diseases,
      representing potential mechanisms to be further validated.

PMID- 26211629
TI  - PLNlncRbase: A resource for experimentally identified lncRNAs in plants.
AB  - Accumulating published reports have confirmed the critical biological role (e.g.,
      cell differentiation, gene regulation, stress response) for plant long non-coding
      RNAs (lncRNAs). However, a literature-derived database with the aim of lncRNA
      curation, data deposit and further distribution remains still absent for this
      particular lncRNA clade. PLNlncRbase has been designed as an easy-to-use resource
      to provide detailed information for experimentally identified plant lncRNAs. In
      the current version, PLNlncRbase has manually collected data from nearly 200
      published literature, covering a total of 1187 plant lncRNAs in 43 plant species.
      The user can retrieve plant lncRNA entries from a well-organized interface
      through a keyword search by using the name of plant species or a lncRNA
      identifier. Each entry upon a query will be returned with detailed information
      for a specific plant lncRNA, including the species name, a lncRNA identifier, a
      brief description of the potential biological role, the lncRNA sequence, the
      lncRNA classification, an expression pattern of the lncRNA, the
      tissue/developmental stage/condition for lncRNA expression, the detection method
      for lncRNA expression, a reference literature, and the potential target gene(s)
      of the lncRNA extracted from the original reference. This database will be
      regularly updated to greatly facilitate future investigations of plant lncRNAs
      pertaining to their biological significance. The PLNlncRbase database is now
      freely available at http://bioinformatics.ahau.edu.cn/PLNlncRbase. 

PMID- 26211630
TI  - Functional conservation and divergence of duplicated fibroblast growth factor
      receptor 1 (fgfr1) genes in blunt snout bream (Megalobrama amblycephala).
AB  - Fgfr1 is a fibroblast growth factor receptor involved in regulating cell growth,
      proliferation, differentiation and migration. Here, we report the isolation and
      characterization of duplicated fgfr1 genes in blunt snout bream (Megalobrama
      amblycephala). Blunt snout bream fgfr1a and -1b cDNAs were found to share a
      relatively high sequence identity of 82%. During embryogenesis, both fgfr1a and 
      1b mRNAs were highly detected at zygotes but gradually decreased and then
      constantly expressed after 16hpf, besides a strong expression for the fgfr1b mRNA
      at 12hpf. Whole-mount in situ hybridization demonstrated that fgfr1a mRNA was
      transcribed at the eyes, mid-hindbrain boundary (MHB), brain, posterior somites
      and tailbud at 16hpf, while the fgfr1b mRNA was only detected at the eyes and
      posterior somites at the same period. At 28hpf embryos, both fgfr1a and -1b mRNAs
      were expressed in the eyes, brain, pharyngeal arches and tailbud, and in the
      eyes, brain, pharyngeal arches and notochord at 55hpf. In adult fish, fgfr1a mRNA
      was strongly expressed in the gill, gonad, brain and midgut, but examined
      relatively low in the skin and kidney. In contrast, the fgfr1b mRNA was highly
      detected in the brain and liver and quite low in the skin, gill and kidney.
      During starvation, both fgfr1a and -1b mRNAs were significantly up-regulated in
      the intestine and liver, but down-regulated in the brain. Moreover, duplicated
      fgfr1 mRNAs were differentially inhibited in tissues with exogenous recombinant
      hGH. Our results suggest that two fgfr1 genes play important roles in regulating
      growth and development in blunt snout bream. 

PMID- 26211631
TI  - Study of radioactive contamination in silts and aerosols at Aldama City, Mexico,
      due to the operation of a yellow-cake processing plant.
AB  - The city of Aldama, Chihuahua, Mexico is located 30 km NNE of Chihuahua city.
      Three high-volume collectors with PM10 heads were placed in specific locations in
      Aldama during the year 2011 to measure radioisotope concentrations in the air.
      The city area of 16 km2 was divided into 64 squares of 500 * 500 m. At the
      vertices of the grid, silt samples were taken between January and June 2011,
      before the rains began. The concentrations of natural, cosmogenic, and
      anthropogenic radioactive isotopes were calculated in both filters and silts
      samples. The isotopes selected for the measurement were 238U, 232Th, (7)Be,
      137Cs, and 40K. Measurements of PM10 and silts were performed during 2011,
      coinciding with the accident at Fukushima, Japan, on March 11. For this reason,
      we could see the 137Cs in PM10 increase between April and July; with the arrival
      of the rains, the 137Cs concentration began to decrease in the air. The
      concentration of PM10 measured by the equipment located at the Mexican Uranium
      plant (URAMEX, initials in Spanish) that was processing radioactive ores exceeded
      the standard values in February and March, when the air velocity increases. At
      City Hall, the concentration of PM10 surpassed the value of the standard between
      May and July. This increased concentration is likely due to increased automobile
      traffic because City Hall is located in the city center. At a private home, the
      concentration of PM10 surpassed the standard on several days during the year
      because the home is located on the outskirts of the city, where most of the
      streets are not paved. Due to the high concentrations of PM10, especially at the
      collection point located at the private home, it is necessary to start taking
      steps to mitigate their spread before they cause health problems in the younger
      population and in older adults.

PMID- 26211632
TI  - Analysis of a landfill gas to energy system at the municipal solid waste landfill
      in Gaziantep, Turkey.
AB  - This paper presents an analysis of the electricity generation from municipal
      solid waste (MSW), via landfill gas valorization technology, at the landfill of
      Gaziantep City, Turkey. Rapid increase in population, and industrial
      developments, throughout the world including Turkey results in larger amount of
      waste materials generated, increased need for energy, and adverse affects on the
      environment and human health. Turkey plans to produce 1/3 of its electricity
      demand using renewable energy sources by the year of 2023. It is recommended to
      use each year around 25 million tonnes of the MSW generated nationwide for a
      renewable energy supply. In this study, a concise summary of current status of
      electricity generation from a MSW landfill gas plant (via biogas harnessing)
      located in Gaziantep City was analyzed as a case study.

PMID- 26211633
TI  - Assessing future scenarios for health care waste management using a multi
      criteria decision analysis tool: A case study in the Turkish West Black Sea
      Region.
AB  - The aim of this paper is to identify the best possible health care waste
      management option in the West Black Sea Region by taking into account economic,
      social, environmental, and technical aspects in the concept of multi-criteria
      decision analysis. In the scope of this research, three different health care
      waste management scenarios that consist of different technology alternatives were
      developed and compared using a decision-making computer software, called Right
      Choice, by identifying various criteria, measuring them, and ranking their
      relative importance from the point of key stakeholders. The results of the study
      show that the decentralized autoclave technology option coupled with the disposal
      through land-filling with energy recovery has potential to be an optimum option
      for health care waste management system, and an efficient health care waste
      segregation scheme should be given more attention by the authorities in the
      region. Furthermore, the discussion of the results points out multidisciplinary
      approach and the equilibrium between social, environmental, economic, and
      technical criteria. The methodology used in this research was developed in order
      to enable the decision makers to gain an increased perception of a decision
      problem. In general, the results and remarks of this study can be used as a basis
      of future planning and anticipation of needs for investment in the area of health
      care waste management in the region and also in developing countries that are
      dealing with the similar waste management problems.

PMID- 26211634
TI  - Investigation of PM2.5 and carbon dioxide levels in urban homes.
AB  - PM2.5 (particulate matter with an aerodynamic diameter <2.5 MUm) samples were
      collected in the indoor environments of 15 urban homes and their adjacent outdoor
      environments in Alexandria, Egypt, during the spring time. Indoor and outdoor
      carbon dioxide (CO2) levels were also measured concurrently. The results showed
      that indoor and outdoor PM2.5 concentrations in the 15 sites, with daily averages
      of 45.5 +/- 11.1 and 47.3 +/- 12.9 ug/m3, respectively, were significantly higher
      than the ambient 24-hr PM2.5 standard of 35 ug/m3 recommended by the U.S.
      Environmental Protection Agency (EPA). The indoor PM2.5 and CO2levels were
      correlated with the corresponding outdoor levels, demonstrating that outdoor
      convection and infiltration could lead to direct transportation indoors.
      Ventilation rates were also measured in the selected residences and ranged from
      1.6 to 4.5 hr-1 with median value of 3.3 hr-1. The indoor/outdoor (I/O) ratios of
      the monitored homes varied from 0.73 to 1.65 with average value of 0.99 +/- 0.26
      for PM2.5, whereas those for CO2ranged from 1.13 to 1.66 with average value of
      1.41 +/- 0.15. Indoor sources and personal activities, including smoking and
      cooking, were found to significantly influence indoor levels.

PMID- 26211635
TI  - Influence of environmental factors on removal of oxides of nitrogen by a
      photocatalytic coating.
AB  - Nitrogen oxides (NOx) emitted from combustion processes have elevated
      concentrations in large urban areas. They cause a range of adverse health
      effects, acid rain, and are precursors to formation of other atmospheric
      pollutants, such as ozone, peroxyacetyl nitrate, and inorganic aerosols.
      Photocatalytic materials containing a semi-conductor that can be activated by
      sunlight, such as titanium dioxide, have been studied for their ability to remove
      NOx. The study presented herein aims to elucidate the environmental parameters
      that most influence the NOx removal efficiency of photocatalytic coatings in hot
      and humid climate conditions. Concrete samples coated with a commercially
      available photocatalytic coating (a stucco) and an uncoated sample have been
      tested in a reactor simulating reasonable summertime outdoor sunlight, relative
      humidity and temperature conditions in southeast Texas. Two-level full factorial
      experiments were completed on each sample for five parameters. It was found that
      contact time, relative humidity and temperature significantly influenced both NO
      and NO2removal. Elevated concentrations of organic pollutants reduced NO removal
      by the coating. Ultra-violet light intensity did not significantly influence
      removal of NO or NO2, however, ultra-violet light intensity was involved in a two
      factor interaction that significantly influenced removal of both NO and NO2.

PMID- 26211637
TI  - Case of basosquamous carcinoma: Dermoscopic and immunohistochemical findings.

PMID- 26211636
TI  - Characterization of air manganese exposure estimates for residents in two Ohio
      towns.
AB  - This study was conducted to derive receptor-specific outdoor exposure
      concentrations of total suspended particulate (TSP) and respirable (dae <= 10 um)
      air manganese (air-Mn) for East Liverpool and Marietta (Ohio) in the absence of
      facility emissions data, but where long-term air measurements were available. Our
      "site-surface area emissions method" used U.S. Environmental Protection Agency's
      (EPA) AERMOD (AMS/EPA Regulatory Model) dispersion model and air measurement data
      to estimate concentrations for residential receptor sites in the two communities.
      Modeled concentrations were used to create ratios between receptor points and
      calibrated using measured data from local air monitoring stations. Estimated
      outdoor air-Mn concentrations were derived for individual study subjects in both
      towns. The mean estimated long-term air-Mn exposure levels for total suspended
      particulate were 0.35 MUg/m3 (geometric mean [GM]) and 0.88 MUg/m3 (arithmetic
      mean [AM]) in East Liverpool (range: 0.014-6.32 MUg/m3) and 0.17 MUg/m3 (GM) and
      0.21 MUg/m3 (AM) in Marietta (range: 0.03-1.61 MUg/m3). Modeled results compared
      well with averaged ambient air measurements from local air monitoring stations.
      Exposure to respirable Mn particulate matter (PM10; PM <10 MUm) was higher in
      Marietta residents.

PMID- 26211638
TI  - Pathogen enrichment device (PED) enables one-step growth, enrichment and
      separation of pathogen from food matrices for detection using bioanalytical
      platforms.
AB  - The bottleneck for accurate detection of foodborne pathogens is separation of
      target analytes from complex food matrices. Currently used sample preparation
      methods are cumbersome, arduous and lengthy; thus, a user-friendly system is
      desirable. A hand-held sample preparation system designated pathogen enrichment
      device (PED) was built that contains a growth chamber, filters, and an ion
      exchange cartridge to deliver bacteria directly onto the detection platforms.
      Escherichia coli O157:H7, Salmonella enterica and Listeria monocytogenes were
      used as model pathogens. Spinach, ground beef, hotdogs, and eggs were used as
      model foods to evaluate PED performance, and results were compared with
      traditional bag enrichment method. Bacterial cells were inoculated at 1, 10, and
      100 CFU/g of the sample and enriched in PED using appropriate pathogen-specific
      selective enrichment broths. The bacterial cell counts in both PED and stomacher
      bag were comparable and the pH in PED-recovered cell suspension was close to
      neutral whereas the pH of cell suspension in the stomacher-bag was slightly
      acidic. The bacterial recovery from the PED was 79-100% and was directly detected
      by lateral-flow immunoassay (LFIA), quantitative PCR (qPCR) and light scattering
      sensor with sample-to-result time of 8-24h with a detection limit of 1CFU/g. In
      qPCR, the amplified PCR products appeared in 4-5 cycles earlier with PED-enriched
      cultures compared to the cultures enriched in stomacher-bag. The hand-held PED
      proved to be a one-step procedure for enrichment and recovery of homogenous
      particle-free bacterial cells for detection using immunological, molecular or
      biosensor-based platforms.

PMID- 26211639
TI  - Association between blood pressure changes during self-paced outdoor walking and
      air temperature.
AB  - Exaggerated elevation of systolic blood pressure (SBP) during exercise is a risk
      factor for future cardiovascular disease. Although there are differences between
      the outdoor exercise and exercise tests in the laboratory setting, there is
      little information regarding SBP changes during practical outdoor exercise. We
      investigated SBP changes during self-paced outdoor walking and the relationship
      to air temperature. Subjects (n = 109, 47-83 years) walked outdoors at their own
      pace wearing a blood pressure monitor on their wrist. SBP increased during
      walking compared to rest, but was higher at the 1 km mark than both the 2 and 3
      km marks (rest, 124 +/- 14 mmHg; 1 km, 140 +/- 16 mmHg; 2 km, 136 +/- 18 mmHg; 3
      km, 135 +/- 18 mmHg). SBP at rest, air temperature, body mass index (BMI) and
      walking intensity during the first 1 km were identified as predictors of SBP at
      the 1 km mark in the stepwise regression analysis, independent of other
      confounders (R2  = 0.606). SBP at the 1 km mark was higher in the lower
      temperature group (11.6-14.3 degrees C, 145 +/- 14 mmHg) than in the intermediate
      (15.1-16.7 degrees C, 140 +/- 18 mmHg) and higher (17.0-19.6 degrees C, 136 +/-
      16 mmHg) temperature groups, independent of SBP at rest, BMI and walking
      intensity. These results suggest that increases in SBP are higher on lower
      temperature days and are greater at 1 km than at 2 and 3 km. It is therefore
      recommended that measures are taken against the cold on lower temperature days to
      attenuate the SBP response during onset of walking.

PMID- 26211640
TI  - The type of feto-placental aneuploidy detected by cfDNA testing may influence the
      choice of confirmatory diagnostic procedure.
AB  - OBJECTIVES: Cell-free DNA (cfDNA) screening can provide false positive/negative
      results because the fetal fraction originates primarily from trophoblast.
      Consequently, invasive diagnostic testing is recommended to confirm a high-risk
      result. Currently, there is debate about the most appropriate invasive method. We
      sought to estimate the frequency in which a chorionic villus sampling (CVS)
      performed after a high-risk cfDNA result would require a follow-up amniocentesis
      due to placental mosaicism. METHODS: Analyses of the frequencies of the different
      types of mosaicism involving cytotrophoblasts, for trisomies 21 (T21), 18 (T18),
      13 (T13) and monosomy X (MX) among 52,673 CVS karyotypes obtained from
      cytotrophoblast, mesenchyme and confirmatory amniocentesis. RESULTS: After a high
      risk cfDNA result for T21, 18, 13 and MX, the likelihood of finding CVS mosaicism
      and need for amniocentesis is, respectively, 2%, 4%, 22% and 59%. When mosaicism
      is detected by CVS, the likelihood of fetal confirmation by amniocentesis is,
      respectively, 44%, 14%, 4% and 26%. CONCLUSIONS: In cases of high-risk cfDNA
      results for T21/T18, CVS (combining cytotrophoblast and mesenchyme analysis) can
      be considered, but with the caveat of 2-4% risk of an inconclusive result
      requiring further testing. In high-risk results for MX/T13, amniocentesis would
      appear to be the most appropriate follow-up diagnostic test, especially in the
      absence of sonographic findings.

PMID- 26211641
TI  - Photoinduced Electron Transfer of Porphyrin Isomers: Impact of Molecular
      Structures on Electron-Transfer Dynamics.
AB  - Porphyrins have been investigated for a long time in various fields of chemistry
      owing to their excellent redox and optical properties. Structural isomers of
      porphyrins have been synthesized, namely, porphycene, hemiporphycene, and
      corrphycene. Although the number of studies on these structural isomers is
      limited, they exhibit interesting properties suitable for various applications
      such as photovoltaic devices, photocatalysts, and photodynamic therapy. In the
      present review, we summarized their photoinduced electron-transfer processes,
      which are key steps of various photofunctions. Their electrochemical and
      photophysical properties are summarized as basic properties for the electron
      transfer. Furthermore, differences among these isomers in the electron-transfer
      processes are clarified, and its origin has been discussed on the basis of their
      molecular structures. 

PMID- 26211642
TI  - Rh(III) -Catalyzed C-H Activation with Pyridotriazoles: Direct Access to
      Fluorophores for Metal-Ion Detection.
AB  - The first C-H bond activation with pyridotriazoles as coupling partners is
      presented using a Rh(III) catalyst. The pyridotriazoles can be used as new
      carbene precursors in C-H activation for direct access to novel fluorescent
      scaffolds. These tunable fluorophores can be applied for the detection of metal
      ions.

PMID- 26211643
TI  - Osteoporosis: Treat or Let Die Twice More Likely.

PMID- 26211644
TI  - Effects of Short-Period Whole-Body Vibration of 20 Hz on Selected Blood
      Biomarkers in Wistar Rats.
AB  - There is a growing interest in the use of vibration generated by
      oscillating/vibratory platforms - also known as whole-body vibration (WBV) - for
      achieving therapeutic, preventative and/or physical performance goals. This study
      investigated the effects of vibration generated by an oscillating platform on the
      concentration of blood biomarkers in rats. Wistar rats (n = 8) were divided in 2
      groups, sedated and individually positioned on an oscillating platform. The
      experimental group (EG) was subjected to vibrations of 20 Hz for one min per day
      for one week while the control group (CG) experienced no vibration. Samples of
      heparinized whole blood were drawn by cardiac puncture for biochemical analysis.
      Concentrations of total cholesterol, triglycerides, HDL, LDL, VLDL, glucose, CK,
      albumin, alkaline phosphates, TGP, TGO, gammaGT, lipase, amylase, urea and
      creatinine were determined. White blood cell count and a platelet hemogram were
      also performed. Following seven sessions of exposure to the vibration, a
      significant (P < 0.05) reduction in gammaGT, VLDL and leukocytes was found. A
      weekly 1-min/day exposure of 20 Hz vibration can was shown to alter the
      concentrations of selected blood biomarkers in rats. The action mechanism
      associated with these effects seems highly complex, but the findings might
      contribute to the understanding of these mechanisms related to the exposure to 20
      Hz vibration. 

PMID- 26211645
TI  - Regulation of Intermittent Hypoxia on Brain Dopamine in Amphetaminized Rats.
AB  - We investigated intermittent hypoxia (IH) on dopamine (DA) release in rat brain
      treated with or without amphetamine (AMPH). Rats were divided into four groups
      including normoxia, IH, AMPH, and AMPH + IH treatments. The cerebrospinal fluid
      (CSF) was collected and the DA levels were detected by high performance liquid
      chromatography (HPLC). The plasma prolactin (PRL) concentration was measured by
      radioimmunoassay (RIA). We found that IH reduced basal DA concentration in media
      prefrontal cortex (mPFC), but increased that in striatum, where DA level was also
      increased in rats treated with AMPH or AMPH + IH. Angiotensin II (Ang II)
      increased the DA release in mPFC and striatum and this effect was enhanced in
      AMPH + IH group. The stimulatory effect of IH on plasma PRL was attenuated in
      presence of AMPH. Tyrosine hydroxylase (TH) expression was decreased by IH, but
      increased by AMPH + IH in mPFC. IH or AMPH treatment decreased the expression of
      vesicular monoamine transporter-2 (VMAT-2) in rat brain. These data suggested
      that IH altered the DA release and changed the protein expression levels in
      different parts of rat brain treated with AMPH. IH may play a role in regulating
      DA metabolism in AMPH addiction. 

PMID- 26211646
TI  - Effects of Indomethacin on Intracellular pH and Na+/H+ Exchanger in the Human
      Monocytes.
AB  - The ability to maintain optimal intracellular pH (pH(i)) is an essential
      requirement for all cells. Na+-H+ exchanger (NHE), a ubiquitously expressed
      transmembrane protein, has been found widely as a major acid extruder in many
      different cell types, including human monocytes. We therefore investigated the
      mechanism of the active pH(i) recovery from intracellular acidosis (induced by
      NH4Cl prepulse) using intracellular 2',7'-bis (2-carboxethyl)-5(6)-carboxyl
      fluorescein (BCECF) fluorescence in cultured human monocytes. Indomethacin is a
      potent, nonselective inhibitor of cyclooxygenases. Due to its toxicity, the
      clinical use of indomethacin as an analgesic-antipyretic agent is limited.
      However, it has recently been found that indomethacin can effectively treat many
      inflammatory/immune disorders. In this study, we further investigated the effect
      of indomethacin on the pHi and explored the underlying mechanism. In HEPES
      (nominally HCO3--free) Tyrode solution, a pH(i) recovery from induced
      intracellular acidosis could be blocked completely by 30 MUM HOE 694, a specific
      NHE1 inhibitor, or by removing [Na+]0. Therefore, in the present study, we
      provided functional evidence, physiologically and pharmacologically, that the
      HCO3--independent acid extruder was mostly likely the NHE1 which was involved in
      acid extrusion in the human monocytes. Moreover, indomethacin (1 MUM-1 mM)
      decreased pH(i) levels in a concentration-dependent manner and significantly
      suppressed the activity of the NHE1, suggesting that indomethacin-induced
      intracellular acidosis is caused both by the inhibition of NHE1 activity and the
      non-specified NHE1-independent acidifying mechanism. In conclusion, our present
      study demonstrates that NHE1 exists functionally in human monocytes, and the
      indomethacin-induced pHi decreasing is summation effects on NHE1-dependent and 
      independent mechanism.

PMID- 26211647
TI  - Optimal Effect of Phenol Block in the Sciatic Nerve of Rats: Standardization of
      Minimized Dosage and Duration of Application.
AB  - The phenol nerve block has been widely used in clinical practice for spasticity
      reduction, but the correlation between the dosage of phenol and its effectiveness
      has seldom been discussed. The objective was to determine the optimal duration of
      phenol in contact with the nervous tissue and to investigate the dose-response
      relationship of 5% aqueous phenol solution by percutaneous nerve block in rats.
      Group I (n = 8) received sciatic nerve block by bathing the nerves in phenol
      solution, and group II (n = 40) by injecting phenol percutaneously. Group IIa to
      IId received different volumes (0.80, 0.16, 0.08 and 0.04 ml) and group IIe
      received normal saline. Compound muscle action potential (CMAP) was measured pre
      injection and at 90 and 270 sec after injection and after surgical exposure of
      the nerves. The duration of CMAP reduced by 10%, 25%, 50%, 75% and 100% after
      phenol injection was also recorded. The mean latency for the evoked response to
      subside in direct phenol application (group I) and percutaneous nerve block
      (group IIa) were 73.5 +/- 5.9 and 62.4 +/- 7.6 sec, respectively. There was no
      statistical difference for the time periods in the blocking effect elicited by
      phenol solution between these two methods. Ninety sec was set as the optimal
      duration for phenol to produce complete conduction blockage. Higher volume of
      phenol produced more significant blocking effect at 90 and 270 sec after
      injection. Percutaneous injection with 0.16 ml of phenol solution had the same
      blocking effect as 0.8 ml. The continuous injection model for percutaneous phenol
      block indeed used significantly more phenol than actually needed. Clinically, the
      progressive injection model can be used to minimize injection volume. 

PMID- 26211648
TI  - Attenuation of Magnesium Sulfate on CoCl2-Induced Cell Death by Activating
      ERK1/2/MAPK and Inhibiting HIF-1alpha via Mitochondrial Apoptotic Signaling
      Suppression in a Neuronal Cell Line.
AB  - Magnesium sulfate (MgSO4) ameliorates hypoxia/ischemia-induced neuronal apoptosis
      in a rat model. This study aimed to investigate the mechanisms governing the anti
      apoptotic effect of MgSO4 on cobalt chloride (CoCl2)-exposed NB41A3 mouse
      neuroblastoma cells. MgSO4 increased the viability of NB41A3 cells treated with
      CoCl2 in a dose-dependent manner. MgSO4 treatment was shown to lead to an
      increase in the anti-apoptotic Bcl-2 family proteins, with a concomitant decrease
      in the pro-apoptotic proteins. MgSO4 also attenuated the CoCl2-induced disruption
      of mitochondrial membrane potential (DeltaPsi(m)) and reduced the release of
      cytochrome c form the mitochondria to the cytosol. Furthermore, exposure to CoCl2
      caused activation of the hypoxia-inducible factor 1alpha (HIF-1alpha). On the
      other hand, MgSO4 markedly reduced CoCl2-induced HIF-1alpha activation and
      suppressed HIF-1alpha downstream protein BNIP3. MgSO4 treatment induced ERK1/2
      activation and attenuated CoCl2-induced activation of p38 and JNK. Addition of
      the ERK1/2 inhibitor U0126 significantly reduced the ability of MgSO4 to protect
      neurons from CoCl2-induced mitochondrial apoptotic events. However, incubation of
      cultures with the p38 and JNK inhibitors did not significantly affect MgSO4
      mediated neuroprotection. MgSO4 appears to suppress CoCl2-induced NB41A3 cell
      death by activating ERK1/2/ MAPK pathways, which further modulates the role of
      Bcl-2 family proteins and mitochondria in NB41A3 cells. Our data suggest that
      MgSO4 may act as a survival factor that preserves mitochondrial integrity and
      inhibits apoptotic pathways.

PMID- 26211649
TI  - Role of Sodium-Hydrogen Exchanger-1 (NHE-1) in the Effect of Exercise on
      Intermittent Hypoxia-Induced Left Ventricular Dysfunction.
AB  - Intermittent hypoxia (IH) occurs frequently in patients with obstructive sleep
      apnoea and can cause ventricular dysfunction. However, whether myocardial
      inflammation and sodium-hydrogen exchanger-1 (NHE-1) expression play an important
      role in IH-induced ventricular dysfunction remains unclear. This study aimed to
      investigate whether short-term exercise provides a protective effect on IH
      induced left ventricular (LV) function impairment. Male Sprague-Dawley rats were
      randomly assigned to 4 groups: control (CON), IH, exercise (EXE) or IH
      interspersed with EXE (IHEXE). IH rats were exposed to repetitive
      hypoxia/reoxygenation cycles (2%-6% O2 for 2-5 s per 75 s, followed by 21% O2 for
      6 h/day) during the light phase for 12 consecutive days. EXE rats were habituated
      to treadmill running for 5 days, permitted 2 days of rest, and followed by 5
      exercise bouts (30 m/min for 60 min on a 2% grade) on consecutive days during the
      dark phase. IHEXE rats were exposed to IH during the light phase interspersed
      with exercise programs during the dark phase on the same day. Cardiac function
      was quantified by echocardiographic evaluation. Myocardial levels of tumour
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and NHE-1 were
      determined. IH rats showed LV dysfunction characterized by lower LV fractional
      shortening (LVFS%) and LV ejection fraction (LVEF%). LV dysfunction was
      associated with higher myocardial levels of TNF-alpha, IL-6 and NHE-1 mRNA and
      protein. These changes were not observed in IHEXE rats (P > 0.05 for all). EXE
      rats showed lower levels of NHE-1 protein than CON rats (P < 0.05). However, the
      levels of LVFS%, LVEF%, TNF-alpha and IL-6 protein and NHE-1 mRNA did not differ
      between EXE and CON rats (P > 0.05 for all). These data indicated that exercise
      may provide a protective effect on IH-induced LV dysfunction by attenuating IH
      induced myocardial NHE-1 hyperactivity. 

PMID- 26211650
TI  - Salivary Immuno Factors, Cortisol and Testosterone Responses in Athletes of a
      Competitive 5,000 m Race.
AB  - The exercise-stress model can be a model of temporary immunosuppression that
      occurs after severe physical and psychological stress. It also allows for the
      study of interactions between the endocrine and the immune systems. This study
      examined changes in salivary hormonal and immune factors in athletes in response
      to physical and psychological stress in a 5,000 m running competition. Eighteen
      endurance-trained runners (9 males and 9 females) participated in this study. All
      participants completed a competitive 5,000 m race. Saliva samples were collected
      10 min before (PRE) and 10 min after (POST) the competition. Saliva was analyzed
      for alpha-amylase activity, concentrations of salivary immunoglobulin A (SIgA),
      lactoferrin, cortisol, testosterone and total protein. Although the
      concentrations of salivary TP, SIgA, lactoferrin, cortisol and alpha-amylase
      activity were significantly increased immediately after a competitive 5,000 m
      race, the secretion rates of these factors were not significantly altered in both
      male and female groups. Additionally, basal levels of SIgA and alpha-amylase
      activity were significantly higher in female runners than in male runners. This
      gender difference still existed after the race. The secretion rates of
      testosterone decreased significantly after the race in the male, but not in the
      female group. Moreover, testosterone-to-cortisol (T/C) ratios were significantly
      lower post-competition compared to pre-competition in both male and female
      athletes. The T/C ratio had been used as a performance index for athletes.
      Whether there are correlations between these changes of their physiological
      characteristics and better running performance need further investigations. 

PMID- 26211651
TI  - Host genetic variants influencing the clinical course of hepatitis C virus
      infection.
AB  - The clinical course of hepatitis C virus (HCV) infection greatly differs in
      individuals. Various viral, host, and environmental factors influence the natural
      history of HCV infection. Recent genome-wide association studies identified
      several host genetic factors influencing treatment efficacy or clinical course in
      HCV infection. A landmark discovery was that IFNL3-IFNL4 variants are strongly
      associated with responses to interferon-based treatment. Genetic variants in
      IFNL3-IFNL4 as well as those in HLA class II loci influence the spontaneous
      clearance of acute HCV infection. Interestingly, these genetic variants also
      affect the activity of hepatitis, or disease progression in chronic hepatitis C.
      In addition, polymorphisms in apoptosis-related genes such as RNF7, TULP1, and
      MERTK are associated with fibrosis progression, and DEPDC5 and MICA variants are
      associated with HCV-related hepatocellular carcinoma. Understanding the genetic
      factors associated with the clinical course of HCV infection is essential for
      personalized treatment and surveillance of disease progression and hepatocellular
      carcinoma.

PMID- 26211652
TI  - Crystal Structure and Desolvation Behaviour of the Tadalafil Monosolvates with
      Acetone and Methyl Ethyl Ketone.
AB  - Crystal structures of Tadalafil (TDF) monosolvated forms with acetone (ACE) and
      methyl ethyl ketone (MEK) were determined by single-crystal X-ray diffraction in
      which same persistent chains of TDF molecules are present as in the reported
      structures. The solvates crystallize in a higher orthorhombic symmetry than the
      known forms with monoclinic structures. Weak interactions between TDF and solvent
      molecules are present in both solvates, leading to slight conformational
      distortions of TDF molecules. The MEK solvate showed slightly higher stability
      than the ACE solvate, regardless of their highly similar molecular conformations
      and crystal packing. Desolvation into anhydrous TDF was achieved by heating,
      exposure to temperature and relative humidity and by mechanical stress. The high
      solubility of TDF in ACE and MEK solvents combined with the ease of desolvation
      of the resulting solvated forms indicates the viability of the solvates use as
      intermediates in the TDF crystallization process.

PMID- 26211653
TI  - Pulmonary artery aneurysms in Behcet's syndrome: a review of the literature with
      emphasis on geographical differences.
AB  - OBJECTIVES: To investigate the frequency of Behcet's syndrome (BS) with pulmonary
      artery aneurysms (PAA) publications, the most lethal complication of BS, as
      reported from different countries and to provide a review of diagnostic
      techniques, treatment approaches and prognosis. METHODS: Countries from each
      continent with a population of 4 million and over were chosen (n=128). A PubMed
      search for "BS, PAA and the country name" was conducted and 23 countries with BS
      and PAA were identified. The full texts of articles (n=91) were analysed for data
      including gender, age, accompanying vascular findings, diagnostic techniques,
      treatment modalities and mortality rates. RESULTS: A total of 207 (183 males, 24
      females) patients with BS and PAA were reported in 91 articles originating from
      23 countries. As expected there was a significant correlation (r=0.88, p<0.001)
      between the total number of articles about BS (n=4431) and those related to PAA
      and BS. In a simple linear regression analysis the number of BS and PAA articles
      from Japan was significantly below the identity line while in Turkey there was a
      propensity to publish more articles related to PAA than expected. One hundred and
      sixteen patients (56%) were treated with immunosuppressive therapy. Biologics
      were used only in 5 patients (2%). Of the 207 patients, 62 (30%) died.
      CONCLUSIONS: PAA is mostly reported as case reports from countries where BS is
      common. PAA might be uncommon in Japan. The prognosis of PAA could be getting
      better.

PMID- 26211654
TI  - Current progress in high cell density yeast bioprocesses for bioethanol
      production.
AB  - High capital costs and low reaction rates are major challenges for establishment
      of fermentation-based production systems in the bioeconomy. Using high cell
      density cultures is an efficient way to increase the volumetric productivity of
      fermentation processes, thereby enabling faster and more robust processes and use
      of smaller reactors. In this review, we summarize recent progress in the
      application of high cell density yeast bioprocesses for first and second
      generation bioethanol production. High biomass concentrations obtained by
      retention of yeast cells in the reactor enables easier cell reuse, simplified
      product recovery and higher dilution rates in continuous processes. High local
      cell density cultures, in the form of encapsulated or strongly flocculating
      yeast, furthermore obtain increased tolerance to convertible fermentation
      inhibitors and utilize glucose and other sugars simultaneously, thereby
      overcoming two additional hurdles for second generation bioethanol production.
      These effects are caused by local concentration gradients due to diffusion
      limitations and conversion of inhibitors and sugars by the cells, which lead to
      low local concentrations of inhibitors and glucose. Quorum sensing may also
      contribute to the increased stress tolerance. Recent developments indicate that
      high cell density methodology, with emphasis on high local cell density, offers
      significant advantages for sustainable second generation bioethanol production. 

PMID- 26211656
TI  - A Striking Case of Enantioinversion in Gold Catalysis and Its Probable Origins.
AB  - The cyclization of the hydroxy-allene 2 to the tetrahydrofuran 3 catalyzed by the
      gold-phosphoramidite complex 1, after ionization with an appropriate silver salt
      AgX, is one of the most striking cases of enantioinversion known to date. The
      major reason why the sense of induction can be switched from (S) to (R) solely by
      changing either the solvent or the temperature or the nature of the counterion X
      is likely found in the bias of the organogold intermediates to undergo assisted
      proto-deauration. Such assistance can be provided by a protic solvent, a
      reasonably coordinating counterion or even by a second substrate molecule itself;
      in this case, the reaction free energy profile gains a strong entropic component
      that can ultimately dictate the stereochemical course. 

PMID- 26211655
TI  - Derivation of water quality standards for carbamazepine, metoprolol, and
      metformin and comparison with monitoring data.
AB  - Environmental quality standards (EQSs) for 3 pharmaceuticals in surface water
      were derived: carbamazepine (epilepsy), metoprolol (heart failure), and metformin
      (diabetes). In recent years, these pharmaceuticals have been detected frequently
      in Dutch surface waters. The proposed standards are based on ecotoxicity data
      from national and European authorization dossiers and additional information
      obtained from open literature. The methods used are in accordance with the
      methodology of the Water Framework Directive and national frameworks for risk
      limit derivation. Only the exposure route regarding direct ecotoxic effects on
      ecosystems could be taken into account for deriving EQSs. The exposure route of
      secondary poisoning of fish-eating animals was not triggered, and not enough data
      were available or accessible to derive an EQS for the exposure of humans due to
      consumption of fish. Monitoring data for surface waters worldwide show that the
      proposed quality standards for carbamazepine may be exceeded. It could be
      expected that when carbamazepine use increases or effluents are diluted less
      during dry seasons, standards will be exceeded more often.

PMID- 26211657
TI  - From Mesomorphic Phosphine Oxide to Clustomesogens Containing Molybdenum and
      Tungsten Octahedral Cluster Cores.
AB  - New clustomesogens (i.e., metal atom clusters containing liquid crystalline (LC)
      materials) have been obtained by grafting neutral cyanobiphenyl (CB)- or
      cholesteryl-containing tailor-made dendritic mesomorphic triphenylphosphine oxide
      ligands on luminescent (M6 Cl(i) 8 )(4+) octahedral cluster cores (M=Mo, W). The
      LC properties were studied by a combination of polarizing optical microscopy
      (POM), differential scanning calorimetry (DSC), and X-ray powder diffraction
      analyses. While the organic ligands showed various mesophase types ranging from
      nematic, SmA columnar (SmACol ), SmA, and SmC phases, it turned out that the
      corresponding clustomesogens formed layered phases (SmA) over a wide range of
      temperatures that depend on the nature and density of mesogenic groups employed.
      Intrinsic luminescence properties of the cluster precursors are preserved over
      the entire range of LC phase existence. 

PMID- 26211658
TI  - Elusive intraoptic nerve foreign body.

PMID- 26211659
TI  - Attitudes to supervised exercise therapy.

PMID- 26211660
TI  - Intravenous Preload of Mesenchymal Stem Cells Rescues Erectile Function in a Rat
      Model of Cavernous Nerve Injury.
AB  - INTRODUCTION: We evaluated the potential preventive effects and mechanisms of
      intravenously preloaded mesenchymal stem cells (MSCs) for erectile dysfunction
      (ED) in a cavernous nerve (CN) injury model. METHODS: Male Sprague-Dawley (SD)
      rats were used for this study. Rats were randomized into two groups. One group
      was intravenously preloaded with MSCs (1.0 * 10(6) cells in 1 mL total fluid
      volume) and the other was infused with medium alone (1 mL Dulbecco's modified
      Eagle's medium [DMEM]) for sham control, respectively. Crushed CN injury was
      induced immediately after infusion. The surgeon was blind to the experimental
      conditions (MSC or medium). MAIN OUTCOME MEASURES: To assess erectile function,
      we measured the intracavernous pressure (ICP) and arterial pressure (AP) at 1
      hour and 2 weeks after CN injury. After measuring the initial ICP/AP of pre
      injury (normal) male SD rats, they were randomized into the two groups and
      infused with MSCs or medium. PKH26-labelled MSCs were used for tracking. To
      investigate the mRNA expression levels of neurotrophins in the major pelvic
      ganglia (MPG), we performed real-time quantitative real-time polymerase chain
      reaction. RESULTS: The reduction of ICP/AP and area under the curve of ICP (ICP
      AUC) in the MSC group was significantly lower than in the DMEM group (P < 0.05; P
      < 0.05) at 1 hour. The ICP/AP and ICP-AUC at 2 weeks post-injury in the MSC group
      was significantly higher than in the DMEM group (P < 0.01; P < 0.05). The
      preloaded PKH26-labelled MSCs were detected in the MPG and CN using confocal
      microscopy indicating homing of the cells to the injured nerve and ganglia. Glia
      cell-derived neurotrophic factor (GDNF) and neurturin, which are important
      neurotrophic factors for erection, had expression levels in MPG significantly
      higher in the MSC group than in the DMEM group (P < 0.01, 0.05). CONCLUSION:
      Intravenous preload of MSCs before a CN injury may prevent or reduce experimental
      ED.

PMID- 26211662
TI  - Developing Streptomyces venezuelae as a cell factory for the production of small
      molecules used in drug discovery.
AB  - The heterologous expression of biosynthetic pathways is an indispensable tool for
      drug discovery and development from natural products. Streptomyces venezuelae is
      a promising heterologous host as it offers several attractive advantages, such as
      rapid growth rate, convenient genetic manipulation, and an abundant supply of
      common biosynthetic building blocks. In recent decades, several S. venezuelae
      mutant strains have been constructed and used to facilitate the synthesis and
      derivatization of diverse natural products. In this review article, we have
      provided a schematic look at these host strains, which were used to synthesize
      natural products from genetically engineered biosynthetic gene clusters. 

PMID- 26211661
TI  - Long-term effects of mental disorders on employment in the National Comorbidity
      Survey ten-year follow-up.
AB  - PURPOSE: Although significant negative associations of mental disorders with
      employment have been documented in epidemiological research, much of this
      research was based on cross-sectional samples and focused only on severe and
      persistent mental disorders. The present study examined the longitudinal
      associations of more common mental disorders with employment. METHODS: Data on
      the associations of common mental disorders with employment are presented here
      from 4501 respondents in the National Comorbidity Survey panel study, a two-wave
      community epidemiological survey of respondents aged 15-54 at baseline (1990
      1992) who were re-interviewed in 2001-2003 and were employed, unemployed in the
      labor force or student at baseline. Lifetime mental disorders at baseline and
      disorders with onset after baseline were assessed with the Composite
      International Diagnostic Interview, a fully structured interview that assessed
      lifetime prevalence of internalizing fear disorders (panic, phobias),
      anxiety/misery disorders (major depression, generalized anxiety disorder, post
      traumatic stress disorder), externalizing disorders (conduct disorder, alcohol
      and illicit drug abuse-dependence), and bipolar disorder. RESULTS: Both baseline
      lifetime disorders and disorders with onsets after baseline were associated with
      significantly reduced odds of subsequent employment among respondents who were
      either employed or students at baseline. Population projections based on the
      assumption that these associations represented causal effects suggest that the
      mental disorders considered here were associated with 1.7-3.2 million adults
      being unemployed in the US population at follow-up. CONCLUSIONS: Expanded access
      to treatment among current employees and students with mental disorders might
      lead to improved employment outcomes in these segments of the population.

PMID- 26211663
TI  - Human papillomavirus type-18 prevalence in oesophageal cancer in the Chinese
      population: a meta-analysis.
AB  - Globally, the prevalence of oesophageal cancer cases is particularly high in
      China. Since 1982, oncogenic human papillomavirus (HPV) has been hypothesized as
      a risk factor for oesophageal cancer, but no firm evidence of HPV infection in
      oesophageal cancer has been established to date. We aimed to conduct a meta
      analysis to estimate the high-risk HPV-18 prevalence of oesophageal cancer in the
      Chinese population. Eligible studies published from 1 January 2005 to 12 July
      2014 were retrieved via computer searches of English and Chinese literature
      databases (including Medline, EMBASE, Chinese National Knowledge Infrastructure
      and Wanfang Data Knowledge Service Platform). A random-effects model was used to
      calculate pooled prevalence and corresponding 95% confidence intervals (CIs). A
      total of 2556 oesophageal cancer cases from 19 studies were included in this meta
      analysis. Overall, the pooled HPV-18 prevalence in oesophageal cancer cases was
      4.1% (95% CI 2.7-5.5) in China, 6.1% (95% CI 2.9-9.3) in fresh or frozen biopsies
      and 4.0% (95% CI 2.3-5.8) in paraffin-embedded fixed biopsies, 8.2% (95% CI 4.6
      11.7) by the E6/E7 region and 2.2% (95% CI 0.9-3.6) by the L1 region of the HPV
      gene. This meta-analysis indicated that China has a moderate HPV-18 prevalence of
      oesophageal cancer compared to cervical cancer, although there is variation
      between different variables. Further studies are needed to elucidate the role of
      HPV in oesophagus carcinogenesis with careful consideration of study design and
      laboratory detection method, providing more accurate assessment of HPV status in
      oesophageal cancer. 

PMID- 26211664
TI  - [A case of acute disseminated encephalomyelitis (ADEM) with an anti
      galactocerebroside antibody].
AB  - Acute disseminated encephalomyelitis (ADEM) with an anti-galactocerebroside
      antibody is very rare. We report a case of 82-year-old man with ADEM associated
      with anti-galactocerebroside antibody in serum. He was admitted to our hospital
      after developing disturbed consciousness and respiratory failure. A cerebrospinal
      fluid examination disclosed an albuminocytologic dissociation and elevation of
      myelin basic protein. Magnetic resonance images revealed lesions in the medulla
      oblongata, pons, midbrain, bilateral cerebellar hemisphere and thalami.
      Initially, he was treated with methylprednisolone (1 g/day) for three days. His
      clinical symptoms improved. We found on 15(th) hospital day that an anti
      galactocerebroside antibody was positive in serum without serological evidence of
      Mycoplasma pneumoniae infection. This case can be diagnosed as ADEM associated
      with an anti-galactocerebroside antibody. 

PMID- 26211665
TI  - Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were
      exposed to ascitic fluid: exploring a new role of haptoglobin in the tumoral
      microenvironment.
AB  - Haptoglobin (Hp) is an acute-phase protein that is produced by the liver to
      capture the iron that is present in the blood circulation, thus avoiding its
      accumulation in the blood. Moreover, Hp has been detected in a wide variety of
      tissues, in which it performs various functions. In addition, this protein is
      considered a potential biomarker in many diseases, such as cancer, including
      ovarian carcinoma; however, its participation in the cancerous processes has not
      yet been determined. The objective of this work was to demonstrate the expression
      of Hp and its receptor CCR2 in the ovarian cancer cells and its possible
      involvement in the process of cell migration through changes in the rearrangement
      of the actin cytoskeleton using western blot and wound-healing assays and
      confirming by confocal microscopy. Ovarian cancer cells express both Hp and its
      receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell
      migration. However, when the cells are exposed to exogenous Hp, the expression of
      CCR2 is induced together with drastic changes in the actin cytoskeleton
      rearrangement. At the same time, Hp induced cell migration in a much more
      efficient manner than did ascitic fluid. These effects were blocked when the CCR2
      synthetic antagonist RS102895 was used to pretreat the cells. These results
      suggest that Hp-induced changes in the cell morphology, actin cytoskeleton
      structure, and migration ability of tumor cells, is possibly "preparing" these
      cells for the potential induction of the metastatic phenotype. 

PMID- 26211667
TI  - A common genetic variant of the chromogranin A-derived peptide catestatin is
      associated with atherogenesis and hypertension in a Japanese population.
AB  - Chromogranin A (CHGA) is a major protein in the secretory granules of chromaffin
      cells. CHGA also gives rise to cardiovascular/metabolism regulatory peptides,
      such as catestatin (CST) and pancreastatin (PST). While CST is a potent inhibitor
      of catecholamine secretion, PST is a potent physiological inhibitor of glucose
      induced insulin secretion. Recently, several SNPs were identified in the CST and
      PST domains of CHGA locus in different populations. Among the discovered SNPs,
      CST variant allele Ser-364 was associated with blood pressure alteration and PST
      variant allele Ser-297 was associated with significantly higher plasma glucose
      level. In this study, we examined whether these CST and PST variant alleles exist
      and influence cardiovascular and metabolic phenotypes in Japanese population. Our
      study comprised of 343 Japanese subjects aged 45-85 years (143 men and 200 women,
      mean age 66 +/- 8 years). We determined the genotypes of CST and PST by PCR
      direct sequencing method and carried out genotype-phenotype association analysis.
      In 343 participants, the minor allele frequency of CST variant Ser-364 was 6.10%.
      On the other hand, we did not detect the PST variant Ser-297 in this entire study
      population. The presence of Ser-364 allele was associated with increased in baPWV
      (an index of systemic arterial stiffness) that suggests an initiation and/or
      progression atherogenesis and hypertension. The Ser-364 allele was also
      associated with elevated systolic blood pressure and pulse pressure, consistent
      with increased baPWV. In conclusion, the CST Ser-364 allele may increase the risk
      for cardiovascular diseases in Japanese population.

PMID- 26211668
TI  - A case of insulinoma with non-alcoholic fatty liver disease: Roles of hyperphagia
      and hyperinsulinemia in pathogenesis of the disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a serious health-related condition
      all over the world; the number of patients is increasing in Asian countries
      including Japan. Better understanding of its pathophysiology is required to
      develop effective therapeutics, as patients may go on to develop non-alcoholic
      steatohepatitis and hepatocellular carcinomas. While NAFLD is believed to be
      associated with metabolic risk factors such as obesity, diabetes, and
      dyslipidemia, its etiology remains largely unknown and the development or co
      existence of NAFLD in patients with insulinoma has not been investigated. A 33
      year-old male with an insulinoma, who had been hypoglycemic during the previous
      four years, developed abnormally elevated levels of liver enzymes and
      histological fatty liver characteristic of NAFLD by the time of admission to our
      hospital for resection of an insulinoma. His medical records for the previous
      eight years revealed that his bodyweight had increased gradually from 60 kg to 71
      kg for seven years and then acutely increased to 79 kg in the latest one-year
      period. This sudden increase was thought to be due to the patient's self
      described overeating of fruits to forestall hypoglycemia. Fresh fruits are rich
      in fructose, and the patient's triglycerides, alanine and aspartate transaminases
      showed an acute increase in the previous one-year period. After resection of the
      insulinoma, the levels of these parameters all were mostly restored, which
      suggests that hyperinsulinemia and subsequent hyperphagia played a role in the
      development of NAFLD in this case. This is the first report of patient with NAFLD
      and an insulinoma. 

PMID- 26211666
TI  - CD4+VEGFR1(HIGH) T cell as a novel Treg subset regulates inflammatory bowel
      disease in lymphopenic mice.
AB  - Regulatory T cells (Tregs) are a specialized subpopulation of T cells that
      control the immune response and thereby maintain immune system homeostasis and
      tolerance to self-antigens. Many subsets of CD4(+) Tregs have been identified,
      including Foxp3(+), Tr1, Th3, and Foxp3neg iT(R)35 cells. In this study, we
      identified a new subset of CD4(+)VEGFR1(high) Tregs that have immunosuppressive
      capacity. CD4(+)VEGFR1high T cells, which constitute approximately 1.0% of CD4(+)
      T cells, are hyporesponsive to T-cell antigen receptor stimulation. Surface
      marker and FoxP3 expression analysis revealed that CD4(+)VEGFR1(high) T cells are
      distinct from known Tregs. CD4(+)VEGFR1(high) T cells suppressed the
      proliferation of CD4(+)CD25(-) T cell as efficiently as CD4(+)CD25(high) natural
      Tregs in a contact-independent manner. Furthermore, adoptive transfer of
      CD4(+)VEGFR1(+) T cells from wild type to RAG-2-deficient C57BL/6 mice inhibited
      effector T-cell-mediated inflammatory bowel disease. Thus, we report CD4(+)
      VEGFR1(high) T cells as a novel subset of Tregs that regulate the inflammatory
      response in the intestinal tract. 

PMID- 26211669
TI  - Embryonic stem cell-derived pancreatic endoderm transplant with MCT1-suppressing
      miR-495 attenuates type II diabetes in mice.
AB  - Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder resulting from
      defects in both insulin secretion and insulin activity. The deficit and
      dysfunction of insulin secreting beta-cells are signature symptoms of T2D.
      Additionally, in pancreatic beta-cells, a small group of genes that are
      abundantly expressed in most other tissues is highly selectively repressed.
      Monocarboxylate transporter 1 (MCT1) is one of these genes. In this study, we
      identified an MCT1-suppressing microRNA (hsa-miR-495) and used this microRNA
      together with human embryonic stem cell (hESC) derived pancreatic endoderm (PE)
      cells transplanted into a high-fat diet induced T2D mouse model. Glucose
      metabolism significantly improved and other symptoms of T2D were attenuated after
      the procedure. Our findings support the potential for T2D treatment using the
      combination of microRNA and hESC differentiated PE cells. 

PMID- 26211670
TI  - Measurement of the entrainment window of islets of Langerhans by microfluidic
      delivery of a chirped glucose waveform.
AB  - Within single islets of Langerhans, the endocrine portion of the pancreas,
      intracellular metabolites, as well as insulin secretion, oscillate with a period
      of ~5 min. In vivo, pulsatile insulin oscillations are also observed with periods
      ranging from 5-15 minutes. In order for oscillations of insulin to be observed in
      vivo, the majority of islets in the pancreas must synchronize their output. It is
      known that populations of islets can be synchronized via entrainment of the
      individual islets to low amplitude glucose oscillations that have periods close
      to islets' natural period. However, the range of glucose periods and amplitudes
      that can entrain islets has not been rigorously examined. To find the range of
      glucose periods that can entrain islets, a microfluidic system was utilized to
      produce and deliver a chirped glucose waveform to populations of islets while
      their individual intracellular [Ca(2+)] ([Ca(2+)]i) oscillations were imaged.
      Waveforms with amplitudes of 0.5, 1, and 1.5 mM above a median value of 11 mM
      were applied while the period was swept from 20-2 min. Oscillations of [Ca(2+)]i
      resonated the strongest when the period of the glucose wave was within 2 min of
      the natural period of the islets, typically close to 5 min. Some examples of 1 :
      2 and 2 : 1 entrainment were observed during exposure to long and short glucose
      periods, respectively. These results shed light on the dynamic nature of islet
      behavior and may help to understand dynamics observed in vivo. 

PMID- 26211671
TI  - The role of experimental and computational structural approaches in 7TM drug
      discovery.
AB  - INTRODUCTION: Starting with the published X-ray structures of ligand-mediated 7TM
      proteins in 2007, experimental approaches, led by X-ray structure determinations,
      and computational approaches, led by docking and molecular dynamics, have
      converged to elaborate our understanding of this field and demonstrate their
      effectiveness in drug discovery. AREAS COVERED: The authors review the structural
      information that has emerged for ligand-mediated 7TM proteins, including the
      class A, B, C, and F receptors, focusing on the 7TM domains for the multi-domain
      proteins. The authors describe the key regions associated with ligand binding as
      well as features responsible for function such as activation versus inhibition
      and biased signaling. Furthermore, the authors summarize the effectiveness of
      computational studies to help clarify the structure-function information and
      their use for drug discovery. EXPERT OPINION: There is now a significant amount
      of structural information covering a range of 7TM protein classes (A, B, C, and
      F) and activation states. For these and closely related proteins, structure-based
      drug discovery has proven to be a powerful tool. More structural information is
      needed with respect to dimerization, 7TM proteins with beta-arrestin to help in
      understanding the control of biased signaling, and full-protein structure
      determinations for non-class A proteins to help in understanding and controlling
      their functioning. Finally, the use of the existing structural information to
      target new sites on these proteins needs further exploration.

PMID- 26211673
TI  - Permanent Ocular Injury Following Paintball Pellet Hit: A Medicolegal Case.
AB  - Paintball is a ubiquitous recreation, with severe and occasionally irreversible
      injuries. In this study, a rare medicolegal case of paintball-related closed
      globe blunt ocular injury was described. An 18-year-old boy who was hit in his
      right eye by a paintball pellet presented with severe eye pain and blurred
      vision. Ophthalmologic examinations showed lid edema, conjunctival hyperemia,
      conjunctival laceration, subconjunctival hemorrhage, corneal edema, anterior
      vitreous hemorrhage, congested sclera, commotio retinae, vitreous hemorrhage,
      retinal hemorrhage, macular edema, and macular hole. After maximum medical
      improvement, the patient who sustained incurable maculopathy and decreased visual
      acuity was referred to the legal medicine center for appraisal of the impairment.
      AMA Guides was used to assess the impairment of the functional vision. Despite
      his monocular visual defect, the patient was rated in the range of mild vision
      loss namely AMA class 1 with 22 percentage visual system impairment. 

PMID- 26211674
TI  - Effects of calcium soap of rice bran oil fatty acids supplementation alone and
      with DL-alpha-tocopherol acetate in lamb diets on performance, digestibility,
      ruminal parameters and meat quality.
AB  - Thirty-six Malpura lambs (28 day old and 6.7 +/- 0.25 kg BW) were distributed
      equally in three groups having six males and six female. They were ad libitum fed
      individually three different experimental diets containing calcium soap of fatty
      acids (CA-FA) at 0 (T1 ) and 40 (T2 and T3 ) g/kg concentrate up to six months of
      age. Animals in T3 were supplemented additionally with 40 mg DL-alpha-tocopherol
      acetate/kg of concentrate. The roughage moiety included ad libitum dry Prosopis
      cineraria and fresh Azadirachata indica leaves. All the lambs were allowed to
      suckle from their dam up to weaning (90 day of age). Supplementation of Ca-FA
      improved weight gain and feed conversion ratio during both pre- (28-90 days) and
      post-weaning (91-180 days) phases; however, no effect of DL-alpha-tocopherol was
      observed. Metabolic parameters during post-weaning phase revealed non-significant
      effect on digestibility but improved nitrogen balance in the test groups. The
      effect on biochemical attributes did not show any significant alteration in
      ruminal parameters, blood biochemicals and urinary purine derivatives. Carcass
      traits revealed higher (p < 0.05) dressing yield and loin eye area with Ca-FA
      supplementation. The value of thiobarbituric reactive substances for nuggets
      prepared from frozen carcasses revealed significant (p < 0.05) reduction in T3
      compared to the other dietary groups. Fatty acid profile of adipose tissue
      revealed higher (p < 0.001) 9-octadecanoic, 9-12-octadecadienoic, polyunsaturated
      fatty acids (PUFA), higher ratio of PUFA/saturated fatty acids (SFA), omega
      6/omega-3 and lower SFA in Ca-FA-supplemented groups. It is concluded that
      supplementation of 40 g/kg calcium soap prepared from industrial grade rice bran
      oil in lamb ration provided additional energy intake, improved N utilization,
      gain and feed conversion ratio besides improving dressing yield and meat quality
      with CLA enriched fatty acid profile. DL-alpha-tocopherol acetate when
      supplemented at 40 mg/kg feed reduced lipid oxidation of meat products thus
      improving its keeping quality. 

PMID- 26211675
TI  - Infectious complications in children with acute lymphoblastic leukemia treated in
      low-middle-income countries.
AB  - Infections are the most important cause of morbidity and mortality in children
      treated for acute lymphoblastic leukemia (ALL). The rates of infection-associated
      mortality are up to 10-times higher in low- and middle-income countries (LMIC)
      than in high-income countries. The prevention, early recognition and management
      of infectious complications is especially challenging in LMIC because of disease
      and poverty-related factors, as well as the shortage of trained personnel,
      supplies, diagnostic tools and adequate organizational infrastructure. Children
      in LMIC with ALL, who are frequently underweight, are at increased risk of
      community-acquired pathogens, nosocomial multidrug-resistant pathogens and
      opportunistic microorganisms. This review summarizes the challenges of managing
      the major categories of infections in children receiving treatment for ALL and
      provides updated practical recommendations for preventing and managing these
      infections in LMIC. 

PMID- 26211677
TI  - Utilization of Kidneys With Acute Kidney Injury in the Extended Criteria Donor
      Setting.

PMID- 26211676
TI  - Interleukin-17A deficiency ameliorates streptozotocin-induced diabetes.
AB  - Interleukin-17 (IL-17) is a cytokine with critical functions in multiple
      autoimmune diseases. However, its roles in type I diabetes and the underlying
      mechanisms remain to be fully elucidated. In the current study, we investigated
      the impact of IL-17 deficiency on streptozotocin (STZ) -induced diabetes. Il-17(
      /-) mice exhibited attenuated hyperglycaemia and insulitis after STZ treatment
      compared with control mice. The Il-17(-/-) mice had fewer CD8(+) cells
      infiltrating the pancreas than wild-type controls after STZ injection. Wild-type
      mice showed increased percentage and number of splenic CD8(+) cells and decreased
      Gr1(+)  CD11b(+) myeloid-derived suppressor cells (MDSC) after STZ treatment, but
      Il-17(-/-) mice maintained the percentages and numbers of splenic CD8(+) cells
      and MDSC, suggesting that IL-17 is implicated in STZ-induced cellular immune
      responses in the spleen. We further purified the MDSC from spleens of STZ-treated
      mice. Il-17(-/-) MDSC showed increased ability to suppress CD8(+) cell
      proliferation in vitro compared with wild-type MDSC. Transfer of MDSC to diabetic
      mice showed that MDSC from Il-17(-/-) mice could ameliorate hyperglycaemia.
      Moreover, recipients with MDSC from Il-17(-/-) mice had a decreased percentage of
      CD8(+) cell in the spleen compared with recipients with MDSC from wild-type mice.
      These data suggest that IL-17 is required in splenic MDSC function after STZ
      delivery. In summary, our study has revealed a pathogenic role of IL-17 in an STZ
      induced diabetes model with important implications for our understanding of IL-17
      function in autoimmune diseases. 

PMID- 26211678
TI  - Dissociative, depressive, and PTSD symptom severity as correlates of nonsuicidal
      self-injury and suicidality in dissociative disorder patients.
AB  - The present study investigates whether symptom severity can distinguish patients
      diagnosed with dissociative identity disorder and dissociative disorder not
      otherwise specified with a recent history of nonsuicidal self-injury (NSSI) and
      suicide attempts from those patients without recent self-harm. A total of 241
      clinicians reported on recent history of patient NSSI and suicide attempts. Of
      these clinicians' patients, 221 completed dissociative, depressive, and
      posttraumatic stress disorder symptomatology measures. Baseline cross-sectional
      data from a naturalistic and prospective study of dissociative disorder patients
      receiving community treatment were utilized. Analyses evaluated dissociative,
      depressive, and posttraumatic stress disorder symptom severity as methods of
      classifying patients into NSSI and suicide attempt groupings. Results indicated
      that dissociation severity accurately classified patients into NSSI and
      suicidality groups, whereas depression severity accurately classified patients
      into NSSI groups. These findings point to dissociation and depression severity as
      important correlates of NSSI and suicidality in patients with dissociative
      disorders and have implications for self-harm prevention and treatment. 

PMID- 26211679
TI  - On the relative roles of background selection and genetic hitchhiking in shaping
      human cytomegalovirus genetic diversity.
AB  - A central focus of population genetics has been examining the contribution of
      selective and neutral processes in shaping patterns of intraspecies diversity. In
      terms of selection specifically, surveys of higher organisms have shown
      considerable variation in the relative contributions of background selection and
      genetic hitchhiking in shaping the distribution of polymorphisms, although these
      analyses have rarely been extended to bacteria and viruses. Here, we study the
      evolution of a ubiquitous, viral pathogen, human cytomegalovirus (HCMV), by
      analysing the relationship among intraspecies diversity, interspecies divergence
      and rates of recombination. We show that there is a strong correlation between
      diversity and divergence, consistent with expectations of neutral evolution.
      However, after correcting for divergence, there remains a significant correlation
      between intraspecies diversity and recombination rates, with additional analyses
      suggesting that this correlation is largely due to the effects of background
      selection. In addition, a small number of loci, centred on long noncoding RNAs,
      also show evidence of selective sweeps. These data suggest that HCMV evolution is
      dominated by neutral mechanisms as well as background selection, expanding our
      understanding of linked selection to a novel class of organisms.

PMID- 26211681
TI  - Pathways to rearrest among court mandated female substance use treatment
      patients.
AB  - BACKGROUND AND OBJECTIVES: Many women who experience substance dependence come
      into contact with the criminal justice system and are mandated by the court to
      enter treatment. Treatment is a viable option and can have many positive
      outcomes, but there remains significant room for improvement. This study was
      designed to identify key risk factors that can be addressed to improve substance
      use treatment outcomes for this population. METHODS: The study sample consisted
      of (n) 381 women who were court mandated to enter substance use treatment.
      Multivariate path analyses were conducted to assess the associations between
      correlates of substance use treatment outcomes, risk for relapse, and rearrest.
      RESULTS: Women who displayed certain demographic risk factors (i.e., less
      educated and unmarried) and had greater levels of substance use severity prior to
      entering treatment experienced elevated risk for relapse. Consequently, women who
      relapsed were nearly three times (OR = 2.50, 95% CI = 1.26-4.93) as likely to be
      rearrested within 12 months of discharge from treatment compared to those who did
      not relapse. DISCUSSION AND CONCLUSIONS: Certain risk factors contribute to
      relapse, which increases risk for rearrest. SCIENTIFIC SIGNIFICANCE: Services
      specifically tailored to women who were court mandated to enter treatment need to
      consider certain demographic risk factors, clinical substance use severity, and
      relapse prevention as key elements to minimize subsequent criminal offending.

PMID- 26211680
TI  - Phosphodiesterase 4D: an enzyme to remember.
AB  - Cyclic adenosine monophosphate (cAMP) is one of the second messengers critically
      involved in the molecular mechanisms underlying memory formation. In the CNS, the
      availability of cAMP is tightly controlled by phosphodiesterase 4 (PDE4), a
      family of enzymes that degrades the cyclic nucleotide to inactive AMP. Among the
      different PDE4 isoforms, in the last few years PDE4D has been hogging the
      limelight due to accumulating evidence for its crucial role in cognitive
      processes, which makes this enzyme a promising target for therapeutic
      interventions in a variety of pathological conditions characterized by memory
      impairment, such as Alzheimer's disease. In this article, we review the role of
      the cAMP signal transduction pathway in memory formation with a particular focus
      on the recent progress in PDE4D research. 

PMID- 26211682
TI  - Insights into thermoadaptation and the evolution of mesophily from the bacterial
      phylum Thermotogae.
AB  - Thermophiles are extremophiles that grow optimally at temperatures >45  degrees
      C. To survive and maintain function of their biological molecules, they have a
      suite of characteristics not found in organisms that grow at moderate temperature
      (mesophiles). At the cellular level, thermophiles have mechanisms for maintaining
      their membranes, nucleic acids, and other cellular structures. At the protein
      level, each of their proteins remains stable and retains activity at temperatures
      that would denature their mesophilic homologs. Conversely, cellular structures
      and proteins from thermophiles may not function optimally at moderate
      temperatures. These differences between thermophiles and mesophiles presumably
      present a barrier for evolutionary transitioning between the 2 lifestyles.
      Therefore, studying closely related thermophiles and mesophiles can help us
      determine how such lifestyle transitions may happen. The bacterial phylum
      Thermotogae contains hyperthermophiles, thermophiles, mesophiles, and organisms
      with temperature ranges wide enough to span both thermophilic and mesophilic
      temperatures. Genomic, proteomic, and physiological differences noted between
      other bacterial thermophiles and mesophiles are evident within the Thermotogae.
      We argue that the Thermotogae is an ideal group of organisms for understanding of
      the response to fluctuating temperature and of long-term evolutionary adaptation
      to a different growth temperature range. 

PMID- 26211683
TI  - Does displayed enthusiasm favour recall, intrinsic motivation and time
      estimation?
AB  - Displayed enthusiasm has been shown to relate to intrinsic motivation, vitality,
      and positive affect, but its effects on recall performance and time estimation
      have not yet been explored. This research aimed at studying the effects of a
      delivery style characterised by High Enthusiasm (HE) on recall, time estimation,
      and intrinsic motivation. In line with previous studies, effects on intrinsic
      motivation were expected. In addition, higher recall and lower time estimations
      were hypothesised. In two experiments, participants assigned to a HE condition or
      to a normal reading control condition listened to a narrative and to a
      descriptive passage. Then, they were asked to rate perceived time, enthusiasm,
      pleasure, interest, enjoyment and curiosity, before writing a free recall.
      Experiment 1 showed that in the HE condition, participants recalled more, were
      more intrinsically motivated, and expressed lower time estimations compared to
      the control condition. Experiment 2 confirmed the positive effects of HE reading
      compared to normal reading, using different passages and a larger sample.

PMID- 26211684
TI  - Re: "Endovascular Aneurysm Sealing for Infrarenal Abdominal Aortic Aneurysms: 30
      Day Outcomes of 105 Patients in a Single Centre".

PMID- 26211686
TI  - Response to 'Re: Long-term Results of a Randomized Controlled Trial Analyzing the
      Role of Systematic Pre-operative Coronary Angiography before Elective Carotid
      Endarterectomy in Patients with Asymptomatic Coronary Artery Disease'.

PMID- 26211685
TI  - Spatio-temporal Quantification of Carotid Plaque Neovascularization on Contrast
      Enhanced Ultrasound: Correlation with Visual Grading and Histopathology.
AB  - OBJECTIVE/BACKGROUND: To evaluate whether carotid intraplaque neovascularization
      (IPN) can be accurately assessed by two types of quantitative analysis on
      contrast enhanced ultrasound (CEUS), the time intensity curve analysis and the
      analysis of contrast agent spatial distributions, and whether the quantitative
      analysis correlates with semiquantitative visual interpretation and
      histopathology. METHODS: Forty-four plaques in 34 patients were included for CEUS
      examination. A three point score system (absent, moderate, and extensive) was
      used for semiquantitative grading of IPN. Eight spatial quantitative parameters
      were derived, including the IPN area ratio in plaque (AR) and the AR in plaque
      core (AR13). Two temporal quantitative parameters were obtained, namely the
      enhanced intensity in plaque (EI) and the enhanced intensity ratio (EIR).
      Histopathology with CD34 staining for quantification of microvessel density (MVD)
      was performed on 12 plaques excised by carotid endarterectomy. RESULTS: Both
      spatial and temporal parameters were correlated with MVD on histology (AR: r =
      .854; AR13: r = .858; EI: r = .767; EIR: r = .750 [p < .01]), as well as with
      semiquantitative grading (p < .01). Five mutually independent factors were
      condensed from 10 interrelated parameters by using factor analysis, and they
      significantly predicted MVD with an radj value as high as .932 (p = .01).
      CONCLUSION: Both spatial and temporal analysis on CEUS can accurately assess IPN.
      Combining them provides better IPN assessment and may be useful for plaque
      vulnerability evaluation and risk stratification.

PMID- 26211687
TI  - Evaluation of instant desensitization after a single topical application over 30
      days: a randomized trial.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of ProArgin(TM)
      (8% arginine), Gluma((r)) and NovaMin((r)) (5% calcium phosphosilicate) in
      relieving dentinal hypersensitivity immediately and over 30 days following a
      single topical application. METHODS: A three-cell, parallel group randomized
      trial was conducted among 56 patients exhibiting dentinal hypersensitivity with
      tooth as the unit of study. ProArgin(TM) paste, Gluma((r)) Desensitizer and
      NovaMin((r)) paste were applied on randomly assigned teeth in each participant.
      Three stimuli were tested: tactile stimulated by running an explorer and measured
      using VAS (1-10 scale); air blast and cold water stimulated hypersensitivity
      measured using the Schiff Sensitivity Scale at baseline, immediately, 15 days and
      30 days after application. Friedman test and Wilcoxon test were used for within
      group comparisons. Kruskal-Wallis test and Mann-Whitney U test were used for
      between group comparisons. RESULTS: All three groups showed significant
      reductions in hypersensitivity from baseline at all time points (p < 0.05).
      ProArgin(TM) paste elicited a significantly higher reduction in hypersensitivity
      (p < 0.016) compared to Gluma((r)) and NovaMin((r)) for all stimuli at the end of
      30 days. CONCLUSIONS: A single topical application of ProArgin(TM) paste is
      significantly more effective than both a single topical application of Gluma((r))
      and NovaMin((r)) paste in relieving dentinal hypersensitivity immediately and
      over 30 days.

PMID- 26211688
TI  - Structural Model for the Spider Silk Protein Spidroin-1.
AB  - Most reports about the 3-D structure of spidroin-1 have been proposed for the
      protein in solid state or for individual domains of these proteins. A gel-based
      mass spectrometry strategy using collision-induced dissociation (CID) and
      electron-transfer dissociation (ETD) fragmentation methods was used to completely
      sequence spidroins-1A and -1B and to assign a series of post-translational
      modifications (PTMs) on to the spidroin sequences. A total of 15 and 16
      phosphorylation sites were detected on spidroin-1A and -1B, respectively. In this
      work, we present the nearly complete amino acid sequence of spidroin-1A and -1B,
      including the nonrepetitive N- and C-terminal domains and a highly repetitive
      central core. We also described a fatty acid layer surrounding the protein fibers
      and PTMs in the sequences of spidroin-1A and -1B, including phosphorylation.
      Thus, molecular models for phosphorylated spidroins were proposed in the presence
      of a mixture fatty acids/water (1:1) and submitted to molecular dynamics
      simulation. The resulting models presented high content of coils, a higher
      percentage of alpha-helix, and an almost neglected content of 310-helix than the
      previous models. Knowledge of the complete structure of spidroins-1A and -1B
      would help to explain the mechanical features of silk fibers. The results of the
      current investigation provide a foundation for biophysical studies of the
      mechanoelastic properties of web-silk proteins. 

PMID- 26211690
TI  - Gastroenterology: Hepatosplenic T cell lymphoma associated with schistosomiasis.

PMID- 26211689
TI  - The BRAAFF checklist: a new dermoscopic algorithm for diagnosing acral melanoma.
AB  - BACKGROUND: The parallel ridge pattern (PRP) is considered the dermoscopic
      hallmark of acral melanoma (AM). However, it was recently shown that
      approximately one-third of AMs do not display a PRP dermoscopically, rendering
      their detection more troublesome. OBJECTIVES: To investigate the diagnostic
      accuracy of dermoscopic criteria for the diagnosis of AM. METHODS: Dermoscopic
      images of consecutive cases of histopathologically diagnosed AMs and acral naevi
      with histopathological diagnosis or with at least 1 year of follow-up were
      evaluated by three independent investigators for the presence of predefined
      criteria. Crude and adjusted odds ratios and their corresponding 95% confidence
      intervals were calculated by univariate and multivariate logistic regression,
      respectively. Receiver operating characteristic curves were used to choose among
      competing classification schemes. RESULTS: In total 603 lesions (472 naevi and
      131 AMs) were included in the study. A scoring system (named BRAAFF) composed of
      six variables was associated with optimal area under the curve and sensitivity
      for the diagnosis of AM. This method includes four positive (irregular blotches,
      ridge pattern, asymmetry of structures and asymmetry of colours) and two negative
      predictors (furrow pattern and fibrillar pattern). CONCLUSIONS: The BRAAFF
      checklist significantly improves the diagnostic accuracy of dermoscopy for the
      diagnosis of AM.

PMID- 26211691
TI  - Gastroenterology: A case of a false target sign.

PMID- 26211692
TI  - Gastroenterology: Primary intestinal lymphangiectasia of the terminal ileum.

PMID- 26211693
TI  - Hepatobiliary and Pancreatic: Pseudoachalasia from pancreatic cancer.

PMID- 26211694
TI  - Hepatobiliary and Pancreatic: Skin metastases from cholangiocarcinoma mimicking
      herpes zoster.

PMID- 26211695
TI  - Ovarian clear cell carcinoma with plasma cell-rich inflammatory stroma: a clear
      cell carcinoma subgroup with distinct clinicopathological features.
AB  - AIMS: Ovarian clear cell carcinoma has a unique stroma. Although a hyalinized or
      mucoid stroma is more common, the stroma sometimes shows a dense inflammatory
      infiltrate, simulating a dysgerminoma. The aim of this study was to analyse the
      character and significance of the inflammatory stroma. METHODS AND RESULTS:
      Twelve of 60 (20%) clear cell carcinomas showed an inflammatory stroma. The
      inflammatory stroma and hyalinized/mucoid stroma were mutually exclusive.
      Inflammatory cells were predominantly composed of CD138-positive plasma cells. As
      compared with the non-inflammatory cases, the epithelial component frequently
      showed a solid growth pattern and immunoreactivity for cyclooxygenase-2, one of
      the critical proinflammatory enzymes (P < 0.005). These findings were repeated
      after heterotransplantation of three clear cell carcinoma cell lines into athymic
      nude mice. In particular, xenografts of one cell line (JHOC-5) were infiltrated
      by mature plasma cells, indicating that plasma cell differentiation was
      stimulated by JHOC-5 cells, independently of T lymphocytes.
      Clinicopathologically, the frequency of International Federation of Gynaecology
      and Obstetrics stage III was higher in the cases with an inflammatory stroma than
      in those without it (P < 0.01). CONCLUSIONS: Clear cell carcinomas with an
      inflammatory stroma constitute a distinct clinicopathological subgroup. It is
      strongly suggested that tumour cells themselves are responsible for inducing
      inflammation and stimulating plasma cell differentiation in a paracrine manner.

PMID- 26211696
TI  - The effects of SUUR protein suggest its role in repressive chromatin renewal
      during replication in Drosophila.
AB  - Replication of chromosomes is central to heredity. To become available for
      replication machinery, DNA invariably needs to dissociate from chromatin
      proteins. Yet, chromatin landscape must be promptly re-established during or soon
      after replication. Although this process underlies the epigenetic inheritance,
      little is known about its molecular mechanisms. This mini-review is focused on
      Drosophila melanogaster SUppressor of UnderReplication (SUUR) protein, which is
      involved both in replication and chromatin maintenance in polytene tissues.
      Existing data suggest that it is involved in the regulation of chromatin renewal
      during replication. According to this model, SUUR protein moves along the
      chromosomes together with the replication complex. When the replication fork
      enters the repressed, H3K27me3- or H3K9me3-enriched, chromatin, SUUR-containing
      complex slows down the replisome until these histone modifications are properly
      placed on the newly-synthesized DNA strands. Suggested model provides an insight
      into the mechanism of epigenetic information inheritance. This hypothesis could
      be tested by further analysis of the interplay between local enrichment of
      repressive histone modifications and the replication fork progression rate. 

PMID- 26211697
TI  - Influence of a hydrophobic resin coating on the immediate and 6-month dentin
      bonding of three universal adhesives.
AB  - OBJECTIVE: To test the influence of a hydrophobic resin coating (HC) on the
      immediate (24h) and 6-month (6m) microtensile dentin bond strengths (MUTBS) and
      nanoleakage (NL) of three universal adhesives applied in self-etch (SE) or in
      etch-and-rinse (ER) mode. METHODS: Sixty caries-free extracted third molars were
      assigned to 12 experimental groups resulting from the combination of the factors
      "adhesive system" (Scotchbond Universal Adhesive [SBU], 3M ESPE; All-Bond
      Universal [ABU], Bisco Inc.; and G-Bond Plus [GBP], GC Corporation); "adhesive
      strategy" (SE or ER); "hydrophobic resin coating" [HC] (with or without
      Heliobond, Ivoclar Vivadent); and "storage time" (24h or 6m). Specimens were
      prepared for MUTBS testing - (24h) half of the beams were immediately tested
      under tension; and (6m) the other half was stored in distilled water (37 degrees
      C) for 6m prior to testing. For each tooth, two beams were randomly selected for
      NL evaluation for both evaluation times. Data were analyzed for each adhesive
      system using three-way ANOVA and Tukey's post-hoc test (alpha=0.05). RESULTS:
      MUTBS: (24h): In SE mode, HC resulted in statistically greater mean MUTBS for all
      adhesives. (6m): When HC was not used the mean MUTBS for SBU/ER, ABU/ER, GBP/ER
      and SBU/SE decreased significantly. NL: (24h): SBU/ER, ABU/ER and GBP/SE resulted
      in a significant reduction in NL when HC was applied. (6m): No significant
      reduction was observed for SBU/ER or for SBU/SE regardless of the use of HC.
      SIGNIFICANCE: The application of a hydrophobic resin coating improved the 24h and
      the 6m performances of all three adhesives systems in SE mode.

PMID- 26211698
TI  - The effect of spark plasma sintering on lithium disilicate glass-ceramics.
AB  - OBJECTIVES: To evaluate the effects of spark plasma sintering (SPS) on the
      microstructure of lithium disilicate glass-ceramics. METHODS: IPS e.max CAD glass
      ceramic samples were processed using spark plasma sintering (SPS) and
      conventionally sintered (CS) as a comparison. Specimens were sintered at varying
      temperatures (T1: 840 degrees C, T2: 820 degrees C, T3: 800 degrees C), heating
      rates (HR1: 150 degrees C/min, HR2: 300 degrees C/min, HR3: 500 degrees C/min)
      and pressures (P1: 15MPa, P2: 50MPa, P3: 70MPa). IPS e.max Press glass powder
      samples were densified at 750 and 800 degrees C (50 or 200MPa pressure). Samples
      were characterized using XRD, HTXRD, and SEM and quantitative image analysis.
      RESULTS: There was a significant increase in median crystal size (MCS) between
      the CS and the SPS T1 groups. A statistical difference (p>0.05) in MCS between
      SPS T1 and SPS T2 groups was observed. The SPS HR3 sample produced a smaller MCS
      than the CS, SPS HR1 and HR2 groups (p<0.05). The SPS P3 sample had a reduction
      in MCS compared with the CS group (p<0.05). XRD of the SPS samples revealed major
      lithium disilicate/lithium metasilicate phases and minor lithium orthophosphate
      and cristobalite/quartz phases. Densified IPS e.max Press glass samples resulted
      in fine fibrils or graduated lithium disilicate crystals. SIGNIFICANCE: The
      effects of SPS were used to refine the microstructure of IPS e.max CAD lithium
      disilicate glass-ceramics. Densification by SPS of IPS e.max Press glass resulted
      in textured and fine nano-crystalline microstructures. SPS generated glass
      ceramic microstructures may have unique properties and could be useful in the
      production of CAD/CAM materials for dentistry.

PMID- 26211699
TI  - Essential steps in the performance of safe retroperitoneal aortic surgery.
AB  - Endovascular stent grafting has become the primary modality when assessing
      patients for treatment of abdominal aortic aneurysms (AAA). The traditional open
      approach is transperitoneal (TP) but many suggest the retroperitoneal method (RP)
      has significant benefits. Retroperitoneal aortic surgery may be unfamiliar to
      many surgeons as they have been trained in the TP approach. This paper provides
      specific tips for the critical steps of this approach enabling it to be performed
      with ease and minimal morbidity. 

PMID- 26211700
TI  - Sodium-glucose cotransporter 2 inhibitor-associated diabetic ketoacidosis: Report
      of two cases with hyperglycemic ketoacidosis in type 1 diabetes.

PMID- 26211701
TI  - Research and development of therapeutic mAbs: An analysis based on pipeline
      projects.
AB  - As the subject of active research and development (R&D) in recent decades,
      monoclonal antibodies have emerged among the major classes of therapeutic agents
      for treatment of many human diseases, especially cancers, infections, and
      immunological disorders. This article surveys the landscape of R&D projects of
      therapeutic monoclonal antibodies (mAbs), which are mostly used for disease
      immunotherapy, from a number of perspectives, including therapeutic indications,
      development phases, participants, and citation of related patents. The results of
      this research can be used as a reference resource for pharmaceutical researchers,
      investors, and policymakers in the field of therapeutic mAbs. 

PMID- 26211702
TI  - Comparison of repeatability between intraoral digital scanner and extraoral
      digital scanner: An in-vitro study.
AB  - PURPOSE: The aim of this study was to compare the repeatability of intraoral
      digital impression scanning with the repeatability of extraoral scanning by using
      Geomagic Qualify 12 as the software of analysis. METHODS: One Nissin Dental Study
      Model (upper jaw) with prepared abutments were designed to form 5 set of
      arrangements according to the layout of prepared abutments (arrangement 1: single
      prepared maxillary central incisor; arrangement 2: single prepared maxillary
      first molar; arrangement 3: prepared central incisor and canine with the lateral
      incisor absent; arrangement 4: half of upper arch with 7 prepared teeth;
      arrangement 5: entire upper arch with 14 prepared teeth). Each arrangement of
      Nissin Dental Study Model was scanned by TRIOS intraoral digital scanner
      (experimental group) and D800 extraoral scanner (control group) for 10 times
      exporting 100 STL files in total. The data were processed and analyzed using
      Geomagic Qualify 12 software to evaluate the repeatability of intraoral digital
      scanning. RESULTS: 3D standard deviations were 13.33, 7.0, 16.33, 41.56, 88.44
      MUm for arrangements 1-5 respectively in experimental group and 14.89, 8.67,
      24.33, 14.22, 12.67 MUm for arrangements 1-5 respectively in the control group.
      Mann-Whitney test revealed a significant difference between the 2 groups with
      regard to arrangements 2-5 (p<0.05). CONCLUSIONS: Precision decreases with the
      increased scanning scope. Precision was clinically acceptable when scanning scope
      was less than half arch. Precision of extraoral scanning was acceptable in
      scanning any scope of arch region.

PMID- 26211703
TI  - Color and gloss evaluation of titanium dioxide coating for acrylic resin denture
      base.
AB  - PURPOSE: We examined the clinical appearance (color, gloss, and surface
      roughness) of TiO(2) coating on polymethyl methacrylate (PMMA) resin dentures.
      METHODS: A spraying method, using air brushes, was used to generate thin uniform
      TiO(2) coating. PMMA resin, primer-coated PMMA, and TiO(2)-coated PMMA (with
      primer) specimens were compared. RESULTS: The Commission Internationale de
      l'Eclairage (CIE) color system revealed color variations between the with/without
      coated samples. The TiO(2)-coated PMMA specimen displayed high levels of
      glossiness, highlighting the efficient self-cleansing actions of the denture. The
      measured surface roughness decreased upon primer coating, and increased following
      TiO(2) coating. CONCLUSIONS: The thin TiO(2) coating afforded high levels of
      glossiness while maintaining the color of the denture base material.

PMID- 26211704
TI  - Investigation of a combined microdroplet generator and pneumatic nebulization
      system for quantitative determination of metal-containing nanoparticles using
      ICPMS.
AB  - In this work, a routinely applicable approach is presented to characterize metal
      NPs. Individual droplets generated from a microdroplet generator (MDG) were
      merged into an aerosol generated by a pneumatic nebulizer (PN) and introduced
      into an ICPMS. The MDG offers high transport efficiency of individual and
      discrete droplets and was therefore used to establish a calibration function for
      mass quantification of NPs which were introduced through the PN following the
      single particle procedure as described elsewhere. The major advantages of such a
      combined configuration include fast processing of large sample volumes, fast
      exchanges of different sample matrixes, and the calibration of the NP signal
      using traceable elemental standards, thus avoiding the need to use NP reference
      materials or other, not always thoroughly characterized, commercially available
      NPs. The transport efficiency of the sample introduction is calculated based on
      the fact that 100% of the calibrant reaches the plasma through the MDG, whereas
      for the PN a NP suspension containing a known number concentration is used.
      Alternatively, bulk analysis of the NP material allows transport efficiency
      determination without any additional information from reference NPs. With this
      method, we could determine the size of standard silver NPs at 60.4 +/- 1.0 nm and
      80.0 +/- 1.4 nm, respectively, which agrees with the size ranges given by the
      supplier (60.8 +/- 6.6 nm and 79.8 +/- 5.4 nm). Furthermore, we were also able to
      determine the NPs number concentration of the sample (Ag/Au) with a deviation of
      3.2% the expected value. 

PMID- 26211705
TI  - Costs of ulcerative colitis from a societal perspective in a regional health care
      area in Spain: A database study.
AB  - OBJECTIVES: To estimate the management of UC associated costs from the societal
      perspective in Spain. METHODS: Observational, longitudinal study with
      retrospective data collection based on reviews of outpatient health records.
      Socio-demographic, clinical and sick leave information was gathered. Patients
      diagnosed of UC between 2002 and 2012, older than 18 years, followed-up by a
      minimum of 12 months post diagnosis, with at least two clinical and use of
      resources data recorded, were included. RESULTS: 285 UC patients [51.2% men; 44.5
      (SD: 15.6) years old; 88.4% without family history of UC; 39.3% proctitis; 5.6
      (2.5) years disease follow-up] participated. More than half (65.6%) were active
      workers, 75.9% were on sick leave for reasons different from UC [mean 0.66 (0.70)
      times per year] during (mean) 28.43 (34.45) days. Only 64 patients were on UC
      related sick-leaves, lasting (mean) 26.17 (37.43) days. Absenteeism due to
      medical visits caused loss of 29.55 (21.38) working hours per year. Mean direct
      and indirect annual cost per UC patient were ?1754.10 (95%CI: 1473.37-2034.83)
      and ?399.32 (282.31-422.69), respectively. Absenteeism was estimated at
      ?88.21(32.72-50.06) per patient per year, in which sick-leaves were the main
      component of indirect costs (88.2%). Age, UC family history, diarrhea at
      diagnosis, blood and blood-forming organs diseases and psychological disorders
      were the main predictors of indirect costs. CONCLUSIONS: UC is a costly disease
      for the society and the Spanish National Healthcare System. Indirect costs imply
      a major burden by affecting the most productive years of patients. Further
      research is needed considering all components of productivity loss, including
      presenteeism-associated costs.

PMID- 26211706
TI  - Six screening instruments for frailty in older patients qualified for emergency
      abdominal surgery.
AB  - INTRODUCTION: The literature on geriatric assessment in emergency admitted
      patients is scarce, particularly there are no studies regarding the efficacy of
      frailty screening tests among patients qualified for emergency abdominal surgery.
      Therefore, the aim of this study was to compare the diagnostic accuracy of six
      screening instruments in this group of patients. MATERIAL AND METHODS: The
      diagnostic accuracy of the Vulnerable Elderly Survey (VES-13), Triage Risk
      Screening Tool (TRST), Geriatric-8 (G8), Groningen Frailty Index (GFI), Rockwood,
      Balducci score was evaluated in a prospective group of 184 consecutive patients
      >=65 years of age. Outcome measure was sensitivity, specificity, positive and
      negative predictive values of these tests in prediciting 30-day postoperative
      outcome. RESULTS: Patients mean age was 76.9+/-5.8 (65-100) years. The prevalence
      of frailty, as diagnosed by screening methods, was: 50-79.9% (Balducci/Rockwood
      G8). Multivariate analyses have identified all screening tests apart from
      Rockwood and TRST as independent factors that predict postoperative outcome. The
      sensitivity and negative predictive value in case of postoperative mortality were
      60-91% (Rockwood-VES-13) and 30-93% (GFI-VES13). In case of postoperative
      morbidity they were 52-85% (Rockwood-VES-13 and G8) and 44-70% (Rockwood-VES-13),
      respectively. CONCLUSION: Considering these results, it is possible to perform
      safely and efficiently screening test for frailty in older patients qualified for
      emergency abdominal surgery. The VES-13 was the best screening instrument; it had
      the highest sensitivity and negative predictive value both for the postoperative
      mortality and morbidity. This instrument may offer physicians additional
      information that can be used in the postoperative optimisation of the treatment
      of these high-risk group of patients.

PMID- 26211707
TI  - Incident Diabetes With Statins: Biology, Artifact, or Both?

PMID- 26211708
TI  - Bivalirudin vs Heparin in Patients Who Undergo Transcatheter Aortic Valve
      Implantation.
AB  - BACKGROUND: We aimed to compare safety and efficacy of the direct thrombin
      inhibitor bivalirudin with unfractionated heparin (UFH) during transcatheter
      aortic valve implantation (TAVI). METHODS: In this retrospective analysis, 461
      patients underwent TAVI between 2007 and 2012; 339 patients received bivalirudin,
      and 122 patients received UFH. In the bivalirudin group, the Sapien XT valve was
      implanted in 159 (46.9%) patients, and 180 (53.1%) received a Medtronic
      CoreValve. In the UFH group, only the Medtronic CoreValve was implanted. The
      primary outcome of interest was the incidence of any bleeding. Secondary outcomes
      of interest were all-cause mortality and cardiovascular mortality at 72 hours
      after the procedure and at 30 days. RESULTS: No significant difference between
      the groups was observed for life-threatening bleeding (2.4% for bivalirudin vs
      3.3% for UFH; P = 0.59), major bleeding (8.3% vs 8.2%, respectively; P = 0.98)
      and minor bleeding (8.3% vs 7.4%, respectively; P = 0.76). At 72 hours after the
      procedure, all-cause mortality was 3.0% in the bivalirudin group and 3.3% for the
      UFH group (P = 0.88), whereas cardiovascular mortality was 3.0% in the
      bivalirudin group and 2.5% in the heparin group (P = 0.77). At 30 days, all-cause
      mortality was 5.3% vs 4.1% in the bivalirudin and heparin groups (P = 0.57) and
      cardiovascular mortality was 4.4% vs 2.5% (P = 0.33). Device success (Valve
      Academic Research Consortium 2 composite end point) was 94.0% in the bivalirudin
      treated and 92.6% in the UFH-treated patients (P = 0.60). The early safety at 30
      days was 85.3% in the bivalirudin-treated group compared with 83.6% in the UFH
      treated group (P = 0.65). CONCLUSIONS: Bivalirudin has a safety and efficacy
      profile similar to weight-adjusted UFH during the TAVI procedure.

PMID- 26211709
TI  - Effect of Aortic Annulus Size and Prosthesis Oversizing on the Hemodynamics and
      Leaflet Bending Stress of Transcatheter Valves: An In Vitro Study.
AB  - BACKGROUND: There are few data about the patient- and prosthesis-related factors
      influencing the hemodynamics of transcatheter heart valves (THVs). The objective
      of this in vitro study was to assess the effect of aortic annulus size and
      prosthesis oversizing on the valve hemodynamics and estimated leaflet bending
      stress of the Edwards SAPIEN balloon-expandable THV (Edwards Lifesciences,
      Irvine, CA). METHODS: The effective orifice area (EOA) of the 23-mm and 26-mm
      SAPIEN THVs were measured by Doppler echocardiography in a pulse duplicator under
      the following experimental conditions: (1) stroke volume of 20, 30, 50, 70, and
      80 mL and (2) aortic annulus size of 19, 20, 21, and 22 mm for the 23-mm SAPIEN
      and 22, 23, and 24, and 25 mm for the 26-mm SAPIEN. The percentage of valve
      oversizing was calculated as follows: % OS = 100 * [(prosthesis nominal area -
      aortic annulus area)/aortic annulus area], where % OS is the percentage of
      oversizing. The leaflet bending stress was measured by high-speed camera imaging
      of the THV leaflet opening. RESULTS: The 2 independent determinants of valve EOA
      were the aortic annulus diameter (R(2) = 0.33; P < 0.001) and the stroke volume
      (R(2) = 0.63; P < 0.001). The prosthesis size and % OS were not independently
      related to EOA. However, a larger % OS was independently associated with higher
      peak systolic leaflet bending stress (DeltaR(2) = 0.11; P < 0.0001). CONCLUSIONS:
      The hemodynamic performance of THV is in large part determined by the aortic
      annulus diameter in which the valve is deployed. Oversizing (up to 20% in area)
      has no significant effect on valve EOA but is associated with higher leaflet
      bending stress, which might promote faster structural valve degeneration in the
      long term.

PMID- 26211710
TI  - Spontaneous Coronary Artery Dissection Misdiagnosed as Takotsubo Cardiomyopathy:
      A Case Series.
AB  - Spontaneous coronary artery dissection (SCAD) and Takotsubo cardiomyopathy (TTC)
      can both cause myocardial infarction with subsequent normalization of wall motion
      abnormality. Angiograms of patients with TTC at Vancouver General Hospital were
      reviewed for SCAD. Clinical and investigational characteristics were recorded.
      Nine women with nonatherosclerotic SCAD were misdiagnosed as having TTC. Their
      average age was 55 years. Five patients had hypertension and 4 had emotional or
      physical stress. Fibromuscular dysplasia was present in 4 women. Wall motion
      abnormalities corresponded to dissected artery location and subsequently
      resolved. SCAD should be included in the differential diagnosis of patients
      suspected of having TTC and coronary angiograms scrutinized for subtle SCAD. 

PMID- 26211711
TI  - Differential effects of Roux-en-Y gastric bypass surgery on brown and beige
      adipose tissue thermogenesis.
AB  - BACKGROUND: There are numerous reports of increased energy expenditure after Roux
      en-Y gastric bypass (RYGB) surgery in humans and rodent models but the underlying
      mechanisms remain poorly understood. In the present study we assessed at the gene
      expression level whether RYGB leads to recruitment of brown adipose tissue (BAT)
      and/or beige adipose tissue (BeAT) as a means of enhanced facultative
      thermogenesis and increased energy expenditure after surgery. METHODS: Diet
      induced obese male Wistar rats were randomized into RYGB-operated (n=10), sham
      operated ad libitum fed (Sham) (n=7) or sham-operated body weight matched (BWM)
      to RYGB groups (n=7). At a stage of postoperatively stabilized weight reduction,
      BAT (interscapular), subcutaneous (inguinal) and visceral (epididymal and
      perirenal) white adipose tissue (WAT) depots were collected in the fasted state.
      Expression of thermoregulatory genes (UCP1, CIDEA and PRDM16) in BAT and WAT as
      well as specific markers of BeAT (Ear2 and TMEM26) in WAT was analyzed using RT
      qPCR. RESULTS: Compared to Sham rats, UCP1 mRNA expression in BAT was
      significantly reduced in BWM, but not in RYGB rats. No differences in mRNA
      expression were found for thermoregulatory proteins or for markers of BeAT in
      subcutaneous or visceral WAT depots between RYGB and Sham groups. CONCLUSION: The
      compensatory decrease in BAT thermogenic gene expression typically associated
      with body weight loss is attenuated after RYGB which, as opposed to recruitment
      of BeAT, may contribute to overall increases in energy expenditure and weight
      loss maintenance after surgery.

PMID- 26211712
TI  - The role of DNA damage and repair in atherosclerosis: A review.
AB  - The global burden of cardiovascular disease is increasing despite therapeutic
      advances in medication and interventional technologies. Accumulated
      deoxyribonucleic acid (DNA) damage and subsequent repair pathways are now
      increasingly recognised as a causal factor in the initiation and progression of
      atherosclerosis. These molecular alterations have been shown to occur within
      affected vasculature, plaque microenvironment as well as in circulating cells.
      The DNA damage response (DDR) pathway is reliant on post-translational
      modification of sensing proteins which activate a signalling cascade to repair,
      if possible, DNA damaged sites in response to various environmental and
      physiological insults. This review summarises the current evidence for DNA damage
      in atherosclerosis, the key steps involved in the DDR pathway, DNA repair and
      their subsequent effects on atherosclerotic plaques, as well as the therapeutic
      options in managing DNA damage-induced atherosclerosis. 

PMID- 26211714
TI  - Acral Nodular Lesion Following Trauma.

PMID- 26211713
TI  - Endothelin-1 impairs coronary arteriolar dilation: Role of p38 kinase-mediated
      superoxide production from NADPH oxidase.
AB  - Elevated levels of endothelin-1 (ET-1), a potent vasoactive peptide, are
      implicated as a risk factor for cardiovascular diseases by exerting
      vasoconstriction. The aim of this study was to address whether ET-1, at sub
      vasomotor concentrations, elicits adverse effects on coronary microvascular
      function. Porcine coronary arterioles (50-100MUm) were isolated, cannulated and
      pressurized without flow for in vitro study. Diameter changes were recorded using
      a videomicrometer. Arterioles developed basal tone (60+/-3MUm) and dilated to the
      endothelium-dependent nitric oxide (NO)-mediated vasodilators serotonin (1nmol/L
      to 0.1MUmol/L) and adenosine (1nmol/L to 10MUmol/L). Treating the vessels with a
      clinically relevant sub-vasomotor concentration of ET-1 (10pmol/L, 60min)
      significantly attenuated arteriolar dilations to adenosine and serotonin but not
      to endothelium-independent vasodilator sodium nitroprusside. The arteriolar wall
      contains ETA receptors and the adverse effect of ET-1 was prevented by ETA
      receptor antagonist BQ123, the superoxide scavenger Tempol, the NADPH oxidase
      inhibitors apocynin and VAS2870, the NOX2-based NADPH oxidase inhibitor gp91 ds
      tat, or the p38 kinase inhibitor SB203580. However, ETB receptor antagonist
      BQ788, H2O2 scavenger catalase, scrambled gp91 ds-tat, or inhibitors of xanthine
      oxidase (allopurinol), PKC (Go 6983), Rho kinase (Y27632), and c-Jun N-terminal
      kinase (SP600125) did not protect the vessel. Immunohistochemical staining showed
      that ET-1 elicited Tempol-, apocynin- and SB203580-sensitive superoxide
      productions in the arteriolar wall. Our results indicate that exposure of
      coronary arterioles to a pathophysiological, sub-vasomotor concentration of ET-1
      leads to vascular dysfunction by impairing endothelium-dependent NO-mediated
      dilation via p38 kinase-mediated production of superoxide from NADPH oxidase
      following ETA receptor activation. 

PMID- 26211715
TI  - Family Factors and Body Mass Index Among Korean-American Preschoolers.
AB  - PURPOSE: The purpose of this study was to examine family factors related to BMI z
      scores and overweight/obesity among Korean-American (KA) preschoolers. METHODS: A
      cross-sectional study was conducted with 104 KA preschoolers and their mothers in
      the Chicago metropolitan area. KA mothers completed questionnaires and their
      preschool-age children's weights and heights were measured. Hierarchical multiple
      linear regression and multiple logistic regression were performed. RESULTS:
      Twenty-two percent of preschoolers were overweight or obese (BMI >=85th
      percentile). Family factors explained 30% of the variance in the children's BMI z
      scores, with parenting feeding style and family functioning contributing most. In
      logistic regression, children were more likely to be overweight/obese if: a
      family had more children, the mother perceived her child as overweight/obese, and
      the family had regular child routines. CONCLUSION: Health care providers should
      consider the family as one unit of care and use that unit to implement culturally
      appropriate childhood overweight/obesity prevention for Korean-American preschool
      aged children. Parental feeding style and parents' attitudes about child weight
      should be considered when advising Korean-Americans about reducing children's
      overweight/obesity.

PMID- 26211716
TI  - Biomechanical Analysis of the Modified Kessler, Lahey, Adelaide, and Becker
      Sutures for Flexor Tendon Repair.
AB  - PURPOSE: To compare the biomechanical properties of the modified Kessler, Lahey,
      Adelaide, and Becker repairs, which are marked by either a locking-loop or a
      cross-lock configuration. METHODS: Ninety-six lacerated porcine flexor tendons
      were repaired using the respective core suture and an epitendinous repair.
      Biomechanical testing was conducted under static and cyclic loads. Parameters of
      interest were 2-mm gap formation force, displacement during different loads,
      stiffness, maximum force, and mode of failure. RESULTS: The meaningful gap
      formation occurred in all 4 repairs at similar tension loads without any
      significant differences. Maximum force was highest in the Becker repair with a
      considerable difference compared with the modified Kessler and Lahey sutures. The
      Adelaide repair showed the highest stiffness. Overall, the displacement during
      cyclic loading demonstrated similar results with an exception between the Lahey
      and the Adelaide repairs at 10 N load. Failure by suture pull-out occurred in 42%
      in the modified Kessler, in 38% in the Lahey, and in 4% in the Adelaide repairs.
      The Becker repair failed only by suture rupture. CONCLUSIONS: The results of our
      study suggest that the difference between the 4-strand repairs with a cross-lock
      or a locking-loop configuration is minor in regard to gap formation. A strong
      epitendinous suture and the application of core suture pretension might prevent
      differences in gapping. However, the modified Kessler and Lahey repairs had an
      inferior maximum tensile strength and were prone to early failure caused by the
      narrow locking loops with their limited locking power. CLINICAL RELEVANCE: We
      suggest that surgeons should use pre-tension in repaired tendons to improve gap
      resistance and should avoid narrow locking loop anchoring to the tendon.

PMID- 26211717
TI  - Coupled disease-behavior dynamics on complex networks: A review.
AB  - It is increasingly recognized that a key component of successful infection
      control efforts is understanding the complex, two-way interaction between disease
      dynamics and human behavioral and social dynamics. Human behavior such as contact
      precautions and social distancing clearly influence disease prevalence, but
      disease prevalence can in turn alter human behavior, forming a coupled, nonlinear
      system. Moreover, in many cases, the spatial structure of the population cannot
      be ignored, such that social and behavioral processes and/or transmission of
      infection must be represented with complex networks. Research on studying coupled
      disease-behavior dynamics in complex networks in particular is growing rapidly,
      and frequently makes use of analysis methods and concepts from statistical
      physics. Here, we review some of the growing literature in this area. We contrast
      network-based approaches to homogeneous-mixing approaches, point out how their
      predictions differ, and describe the rich and often surprising behavior of
      disease-behavior dynamics on complex networks, and compare them to processes in
      statistical physics. We discuss how these models can capture the dynamics that
      characterize many real-world scenarios, thereby suggesting ways that policy
      makers can better design effective prevention strategies. We also describe the
      growing sources of digital data that are facilitating research in this area.
      Finally, we suggest pitfalls which might be faced by researchers in the field,
      and we suggest several ways in which the field could move forward in the coming
      years. 

PMID- 26211718
TI  - Zinc oxide induces the stringent response and major reorientations in the central
      metabolism of Bacillus subtilis.
AB  - Microorganisms, such as bacteria, are one of the first targets of nanoparticles
      in the environment. In this study, we tested the effect of two nanoparticles, ZnO
      and TiO2, with the salt ZnSO4 as the control, on the Gram-positive bacterium
      Bacillus subtilis by 2D gel electrophoresis-based proteomics. Despite a
      significant effect on viability (LD50), TiO2 NPs had no detectable effect on the
      proteomic pattern, while ZnO NPs and ZnSO4 significantly modified B. subtilis
      metabolism. These results allowed us to conclude that the effects of ZnO observed
      in this work were mainly attributable to Zn dissolution in the culture media.
      Proteomic analysis highlighted twelve modulated proteins related to central
      metabolism: MetE and MccB (cysteine metabolism), OdhA, AspB, IolD, AnsB, PdhB and
      YtsJ (Krebs cycle) and XylA, YqjI, Drm and Tal (pentose phosphate pathway).
      Biochemical assays, such as free sulfhydryl, CoA-SH and malate dehydrogenase
      assays corroborated the observed central metabolism reorientation and showed that
      Zn stress induced oxidative stress, probably as a consequence of thiol chelation
      stress by Zn ions. The other patterns affected by ZnO and ZnSO4 were the
      stringent response and the general stress response. Nine proteins involved in or
      controlled by the stringent response showed a modified expression profile in the
      presence of ZnO NPs or ZnSO4: YwaC, SigH, YtxH, YtzB, TufA, RplJ, RpsB, PdhB and
      Mbl. An increase in the ppGpp concentration confirmed the involvement of the
      stringent response during a Zn stress. All these metabolic reorientations in
      response to Zn stress were probably the result of complex regulatory mechanisms
      including at least the stringent response via YwaC. 

PMID- 26211722
TI  - Surface modification of La(0.8)Sr(0.2)CrO(3-delta)-YSZ dual-phase membranes for
      syngas production.
AB  - Oxygen permeation fluxes were studied in Mixed Ionic and Electronic Conducting
      (MIEC) membranes based on composites of 40 vol% La(0.8)Sr(0.2)CrO3 (LSCr) and 60
      vol% yttria-stabilized zirconia (YSZ), using ambient air and flowing CO to
      establish a P(O2) gradient. The ambipolar conductivity of the dense LSCr-YSZ
      composite was determined for membranes with dense layers that were 115 MUm and
      650 MUm thick. Other parts of the investigation focused on how modifications to
      the surface on the CO side affected the fluxes. Using a porous LSCr-YSZ composite
      on the surface as the base case, oxygen fluxes were shown to increase
      dramatically upon addition of 5 wt% CeO2 as a catalyst and an additional increase
      was observed with 1 wt% Pt. Changes in the structure of the porous composite LSCr
      YSZ surface to improve connectivity of the YSZ phase also led to large increases
      in the oxygen fluxes.

PMID- 26211720
TI  - Identification of Heart Failure Events in Medicare Claims: The Atherosclerosis
      Risk in Communities (ARIC) Study.
AB  - BACKGROUND: We examined the accuracy of Medicare heart failure (HF) diagnostic
      codes in the identification of acute decompensated (ADHF and chronic stable
      (CSHF) HF. METHODS AND RESULTS: Hospitalizations were identified from medical
      discharge records for Atherosclerosis Risk in Communities (ARIC) study
      participants with linked Medicare Provider Analysis and Review (MedPAR) files for
      the years 2005-2009. The ARIC study classification of ADHF and CSHF, based on
      adjudicated review of medical records, was considered to be the criterion
      standard. A total 8,239 ARIC medical records and MedPAR records meeting fee-for
      service (FFS) criteria matched on unique participant ID and date of discharge
      (68.5% match). Agreement between HF diagnostic codes from the 2 data sources
      found in the matched records for codes in any position (kappa > 0.9) was
      attenuated for primary diagnostic codes (kappa < 0.8). Sensitivity of HF
      diagnostic codes found in Medicare claims in the identification of ADHF and CSHF
      was low, especially for the primary diagnostic codes. CONCLUSION: Matching of
      hospitalizations from Medicare claims with those obtained from abstracted medical
      records is incomplete, even for hospitalizations meeting FFS criteria. Within
      matched records, HF diagnostic codes from Medicare show excellent agreement with
      HF diagnostic codes obtained from medical record abstraction. The Medicare data
      may, however, overestimate the occurrence of hospitalized ADHF or CSHF.

PMID- 26211721
TI  - Increased Serum Levels of the Notch Ligand DLL1 are Associated with Diastolic
      Dysfunction, Reduced Exercise Capacity, and Adverse Outcome in Chronic Heart
      Failure.
AB  - BACKGROUND: Notch receptors and ligands have been demonstrated in myocardial
      tissue in experimental as well as clinical heart failure (HF), and a role for
      Notch signaling in myocardial remodeling and disease progression may be
      anticipated. We hypothesized that serum levels of the Notch ligand Delta-like-1
      (DLL1) would be associated with clinical and hemodynamic variables in patients
      with HF. METHODS AND RESULTS: We measured serum DLL1 in 183 patients with chronic
      HF and 50 age- and sex-matched healthy control subjects by means of enzyme
      immunoassay. Our main findings were that (i) HF patients had significantly higher
      serum DLL1 levels than healthy control subjects, (ii) DLL1 levels were
      significantly correlated with neurohormonal activation, systemic inflammation,
      and impaired kidney function, (iii) high DLL1 levels were associated with
      diastolic dysfunction and reduced exercise capacity, but not with impaired
      systolic function, and (iv) in univariate analysis, but not after multivariable
      adjustment, high levels of DDL1 were associated with adverse outcome.
      CONCLUSIONS: Our findings may imply that DLL1 and the Notch signaling pathways
      are involved in the pathophysiology of HF, potentially affecting diastolic
      function.

PMID- 26211723
TI  - Editorial: Diffuse large B-cell lymphoma: survival of the fittest?

PMID- 26211724
TI  - Impact of body mass index, gender, and smoking on thickness of free soft tissue
      flaps used for orofacial reconstruction.
AB  - Donor-site selection may play an important role in the reconstruction of large
      orofacial defects. The thickness and structure of transplanted tissue has to fit
      those of the recipient site to achieve a satisfactory outcome. To evaluate the
      thickness of free flaps that are frequently used for orofacial reconstruction and
      its association with body mass index (BMI), gender, and smoking, a prospective
      study was conducted. A total of 122 volunteers were included in the study, and
      their data regarding BMI, gender, and tobacco use were documented.
      Ultrasonography was used to evaluate the thickness of the radial and ulnar
      forearm flaps (RFFF and UFFF, respectively), the scapular and parascapular flaps
      (SF and PSF, respectively), the anterolateral thigh flap (ALT), and the free
      fibular flap (FF). Correlation and regression analysis were performed to assess
      any relationship among parameters and to investigate their effect on flap
      thickness. The UFFF showed the lowest thickness (0.65 +/- 0.16 cm), followed by
      the RFFF (0.83 +/- 0.20 cm). The FF showed a comparable thickness (0.82 +/- 0.26
      cm), followed by the SF (0.99 +/- 0.13 cm) and the PSF (1 +/- 0.14 cm). The ALT
      flap displayed the greatest thickness (1.42 +/- 0.42 cm) and correlated
      especially with BMI and gender, whereas the UFFF was the thinnest with relatively
      constant values, regardless of potential influential factors.

PMID- 26211725
TI  - Development and first clinical application of automated virtual reconstruction of
      unilateral midface defects.
AB  - PURPOSE: Computer-assisted surgery is used for decision making, treatment, and
      quality control throughout the reconstruction process of unilateral midface
      defects. The current approaches exploit the symmetry of the face by mirroring the
      intact side on the defect side using various segmentation methods. All
      commercially available implementations, however, are somewhat time consuming and
      dependent on the level of expertise of the user. We present a method for
      automatic reconstruction of unilateral midface defects using registration.
      MATERIAL AND METHODS: To reconstruct a skull by registration, the defect volume
      has to be virtually deleted from the skull. This modified data set is then
      mirrored and registered onto the original, defect-free skull. The fusion of these
      two skulls is the virtual reconstructed skull bridging the defect. Reconstruction
      by registration was performed for 24 different skulls without motion or dental
      restoration artifacts. Subsequently, simulation was performed with four
      accurately defined, various-sized, defects of the orbito-zygomatic complex. The
      results of the automated virtual reconstructions were compared with those
      obtained for the same defects as determined using conventional atlas-based
      planning software (iPlan). To simulate various clinical situations, four groups
      each containing six skulls were evaluated: the complete skull, midface and
      neurocranium, midface and lower jaw, and midface alone. The differences were
      compared using the similarity coefficients of Sorensen-Dice and Jaccard.
      Statistical analyses were performed using the t-test and Mann-Whitney U test.
      RESULTS: The reconstruction results were similar for all the groups. The Sorensen
      Dice coefficients of similarity for all reconstructed skulls were 0.869 and 0.874
      for the registration and atlas-based reconstructions, respectively. The
      corresponding Jaccard coefficients were 0.774 and 0.781, respectively. Atlas
      based reconstruction showed significantly better results in group 3 (midface and
      lower jaw) alone. CONCLUSION: Virtual automated reconstruction by registration
      had equivalent accuracy to conventional atlas-based reconstruction across a
      spectrum of defects, from simple orbital to complex orbito-zygomatic defects.
      However, for those involving the midface and lower jaw, atlas-based
      reconstruction showed significantly better results. Although the new approach is
      somewhat hardware demanding, it is user independent, dispensing with the need for
      time-consuming adjustments to the results of planning. The first clinical
      application of registration reconstruction revealed performance equivalent to
      that of the conventional approach.

PMID- 26211726
TI  - 6-Hydroxydopamine as a tool to understand adaptive immune system-induced dopamine
      neurodegeneration in Parkinson's disease.
AB  - CONTEXT: Neuroimmunological response is associated with neurodegeneration in the
      human substantia nigra (SN) in Parkinson's disease (PD). OBJECTIVE: To explore
      the possibility that the neurotoxin, 6-hydroxydopamine (6-OHDA), could be used as
      a tool in mice to understand the immune response in PD. MATERIALS AND METHODS: We
      employed unilateral administration of 6-OHDA into the mouse SN. At 1 week, 2
      weeks and 4 weeks post-injection, we used immunohistochemistry for the markers
      Iba-1 and gp91PHOX to investigate activated microglia in the SN. To examine the
      adaptive immune response, we used immunohistochemistry for CD3-positive T
      lymphocytes, CD45R-positive B-lymphocytes and anti-mouse immunoglobulin-G (IgG).
      Dopamine neuron loss was examined using immunohistochemistry for the dopamine
      neuron marker, tyrosine hydroxylase. RESULTS: Compared to vehicle, 6-OHDA
      administration induced an intense IgG deposition in the SN as well as increased
      infiltration of both T- and B- lymphocytes into the injected side of the
      midbrain. The adaptive immune response was associated with extensive destruction
      of dopamine neurons and extensive microglial activation at every time point in
      the 6-OHDA groups. CONCLUSION: Our results suggest that 6-OHDA administration in
      mice can a potential tool for understanding mechanisms underlying adaptive immune
      activation-induced neurodegeneration in PD.

PMID- 26211727
TI  - Synthesis, toxicity study and anti-inflammatory effect of MHTP, a new
      tetrahydroisoquinoline alkaloid.
AB  - The alkaloid 2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)phenol
      (MHTP) was synthesized to prospect new compounds with therapeutic properties.
      Thus, the goal of this study was to evaluate the MHTP anti-inflammatory effect by
      in vivo and in vitro assays. The MHTP toxicity was analyzed. We found that MHTP
      pre-treatment (2.5-10 mg/kg) showed antiedematogenic effect (p < 0.05) in
      carrageenan-induced paw edema by inhibiting the PGE2 action independently of mast
      cell degranulation or histamine activity. MHTP also diminished (p < 0.01) total
      leukocyte migration in 41.5% into peritoneal cavity during carrageenan-induced
      peritonitis, reducing polymorphonuclear cells (PMNs) (59.6%) and proteins levels
      (29.4%). MHTP in an experimental model of acute lung injury inhibited (p < 0.001)
      total inflammatory cell migration into the lungs and PMNs in 58% and 67.5%,
      respectively. Additionally, MHTP did not present cytotoxicity at concentrations
      of 10, 25 or 50 MUM but decreased (p < 0.001) the NO production in 24%, 47% and
      39%, respectively. The alkaloid also reduced (p < 0.001, in lipopolysaccharide
      (LPS)-stimulated macrophages (1 MUg/mL), IL-1beta, IL-6 and IL-10 levels in
      35.7%, 31.0% and 33.4%, respectively. The results obtained in this study allow us
      to conclude that the inedited synthetic alkaloid, MHTP has anti-inflammatory
      effect by inhibiting PGE2 function as well as inhibiting inflammatory cell
      migration to the inflamed site and attenuated the acute lung injury disease by
      inhibiting the migration of neutrophil to the lung. However, further studies will
      be carried out to demonstrate the mechanisms of action of the molecule and
      explore its potential as a future drug to treat inflammatory processes. 

PMID- 26211728
TI  - Chemical components of the Ephedra major from Iran.
AB  - Ephedra is a dioecious shrub that belongs to the Ephedraceae family of
      gymnosperms. Almost all commercial applications of Ephedra extracts are derived
      from the ephedrine alkaloids found in the evergreen stems. The purpose of this
      study was to compare chemical components (total alkaloid, ephedrine, total
      phenol, total flavonoid and tannin) of Ephedra major plants during May to October
      months. The seeds and stems were collected from Bojnoord altitudes in east of
      Iran. Total alkaloid was separated by solvent and soxhelet extraction method. The
      results revealed that solvent extraction method is more efficient than soxhelet
      extraction method. The measurement of chemical components showed significant
      difference during May to October months. Data from HPLC analysis revealed that
      while root is depleted of ephedrine, the ephedrine amount in stem organ ranged
      from 1.50 +/- 0.15 to 2.12 +/- 0.01 mg/g dry weight. The results indicate that E.
      major can be as a suitable source of ephedrine.

PMID- 26211729
TI  - Time-lapse Raman imaging of osteoblast differentiation.
AB  - Osteoblastic mineralization occurs during the early stages of bone formation.
      During this mineralization, hydroxyapatite (HA), a major component of bone, is
      synthesized, generating hard tissue. Many of the mechanisms driving
      biomineralization remain unclear because the traditional biochemical assays used
      to investigate them are destructive techniques incompatible with viable cells. To
      determine the temporal changes in mineralization-related biomolecules at
      mineralization spots, we performed time-lapse Raman imaging of mouse osteoblasts
      at a subcellular resolution throughout the mineralization process. Raman imaging
      enabled us to analyze the dynamics of the related biomolecules at mineralization
      spots throughout the entire process of mineralization. Here, we stimulated KUSA
      A1 cells to differentiate into osteoblasts and conducted time-lapse Raman imaging
      on them every 4 hours for 24 hours, beginning 5 days after the stimulation. The
      HA and cytochrome c Raman bands were used as markers for osteoblastic
      mineralization and apoptosis. From the Raman images successfully acquired
      throughout the mineralization process, we found that beta-carotene acts as a
      biomarker that indicates the initiation of osteoblastic mineralization. A
      fluctuation of cytochrome c concentration, which indicates cell apoptosis, was
      also observed during mineralization. We expect time-lapse Raman imaging to help
      us to further elucidate osteoblastic mineralization mechanisms that have
      previously been unobservable. 

PMID- 26211730
TI  - An Integrative Genomic Study Implicates the Postsynaptic Density in the
      Pathogenesis of Bipolar Disorder.
AB  - Genome-wide association studies (GWAS) have identified several common variants
      associated with bipolar disorder (BD), but the biological meaning of these
      findings remains unclear. Integrative genomics-the integration of GWAS signals
      with gene expression data-may illuminate genes and gene networks that have key
      roles in the pathogenesis of BD. We applied weighted gene co-expression network
      analysis (WGCNA), which exploits patterns of co-expression among genes, to brain
      transcriptome data obtained by sequencing of poly-A RNA derived from postmortem
      dorsolateral prefrontal cortex from people with BD, along with age- and sex
      matched controls. WGCNA identified 33 gene modules. Many of the modules
      corresponded closely to those previously reported in human cortex. Three modules
      were associated with BD, enriched for genes differentially expressed in BD, and
      also enriched for signals in prior GWAS of BD. Functional analysis of genes
      within these modules revealed significant enrichment of several functionally
      related sets of genes, especially those involved in the postsynaptic density
      (PSD). These results provide convergent support for the hypothesis that
      dysregulation of genes involved in the PSD is a key factor in the pathogenesis of
      BD. If replicated in larger samples, these findings could point toward new
      therapeutic targets for BD. 

PMID- 26211732
TI  - Global-change vulnerability of a key plant resource, the African palms.
AB  - Palms are keystone species in tropical ecosystems and provide essential ecosystem
      services to rural people worldwide. However, many palm species are threatened by
      habitat loss and over-exploitation. Furthermore, palms are sensitive to climate
      and thus vulnerable to future climate changes. Here, we provide a first
      quantitative assessment of the future risks to the African palm flora, finding
      that African palm species on average may experience a decline in climatic
      suitability in >70% of their current ranges by 2080. This suitability loss may,
      however, be almost halved if migration to nearby climatically suitable sites
      succeeds. Worryingly, 42% of the areas with 80-100% of species losing climate
      suitability are also characterized by high human population density (HPD). By
      2080, >90% of all African palm species' ranges will likely occur at HPDs leading
      to increased risks of habitat loss and overexploitation. Additionally, up to 87%
      of all species are predicted to lose climatic suitability within current
      protected areas (PAs) by 2080. In summary, a major plant component of tropical
      ecosystems and provider of ecosystem services to rural populations will face
      strongly increased pressures from climate change and human populations in the
      near future. 

PMID- 26211733
TI  - Peripheral neuropathy: an underreported neurologic manifestation of inflammatory
      bowel disease.
AB  - BACKGROUND AND AIMS: One of the most frequent neurologic complications reported
      in inflammatory bowel disease population is peripheral neuropathy; however,
      clinical aspects of peripheral nerve damage are not well characterized. The aim
      of the review is to present the existing literature on peripheral neuropathy in
      inflammatory bowel disease patients. METHODS: A literature search identified the
      publications reporting on epidemiology, clinical features, underlying mechanisms
      and management of ulcerative colitis and Crohn's disease patients with peripheral
      nerve involvement. RESULTS: The pathogenesis of peripheral nervous system damage
      in inflammatory bowel disease has yet to be elucidated, although it seems to be
      related to immune mechanisms; therefore, treatment with immunotherapy is
      recommended. In addition, peripheral neuropathy may appear as iatrogenic-related
      disorders associated with several drugs used in controlling inflammatory bowel
      disease activity; finally, peripheral neuropathy may also be caused by
      micronutrient deficiencies secondary to malabsorption-related disorders.
      CONCLUSIONS: Although peripheral nervous nerve damage associated with
      inflammatory bowel disease is rarely reported, clinicians should be aware of the
      peripheral neuropathy clinical manifestations in order to recognize it and
      provide early treatment, which is crucial for preventing major neurologic
      morbidity. Heightened awareness is necessary for the successful management of
      these patients.

PMID- 26211731
TI  - The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through
      Central GLP-1 Receptors.
AB  - Unconditioned rewarding stimuli evoke phasic increases in dopamine concentration
      in the nucleus accumbens (NAc) while discrete aversive stimuli elicit pauses in
      dopamine neuron firing and reductions in NAc dopamine concentration. The
      unconditioned effects of more prolonged aversive states on dopamine release
      dynamics are not well understood and are investigated here using the malaise
      inducing agent lithium chloride (LiCl). We used fast-scan cyclic voltammetry to
      measure phasic increases in NAc dopamine resulting from electrical stimulation of
      dopamine cell bodies in the ventral tegmental area (VTA). Systemic LiCl injection
      reduced electrically evoked dopamine release in the NAc of both anesthetized and
      awake rats. As some behavioral effects of LiCl appear to be mediated through
      glucagon-like peptide-1 receptor (GLP-1R) activation, we hypothesized that the
      suppression of phasic dopamine by LiCl is GLP-1R dependent. Indeed, peripheral
      pretreatment with the GLP-1R antagonist exendin-9 (Ex-9) potently attenuated the
      LiCl-induced suppression of dopamine. Pretreatment with Ex-9 did not, however,
      affect the suppression of phasic dopamine release by the kappa-opioid receptor
      agonist, salvinorin A, supporting a selective effect of GLP-1R stimulation in
      LiCl-induced dopamine suppression. By delivering Ex-9 to either the lateral or
      fourth ventricle, we highlight a population of central GLP-1 receptors rostral to
      the hindbrain that are involved in the LiCl-mediated suppression of NAc dopamine
      release. 

PMID- 26211734
TI  - Pr-SNTX, a short-chain three-finger toxin from Papuan pigmy mulga snake, is an
      antagonist of muscle-type nicotinic acetylcholine receptor
      (alpha2betadeltaepsilon).
AB  - Three-finger toxins (3FTxs) are one of the major components in snake venoms. In
      this study, we isolated a cDNA encoding a short-chain 3FTx, Pr-SNTX, from
      Pseudechis rossignolii. The amino acid sequence of Pr-SNTX is nearly identical to
      that of its ortholog in Pseudechis australis. Pr-SNTX protein inhibited muscle
      type (alpha2betadeltaepsilon), but not neuronal alpha7 nicotinic acetylcholine
      receptor (nAChR) activity.

PMID- 26211735
TI  - Effects of aromatherapy on sleep quality and anxiety of patients.
AB  - BACKGROUND: In intensive care units (ICUs), patients cannot sleep well.
      Aromatherapy is used for depression, anxiety, relaxation and disorders related
      with sleep and stress. AIM: This study aimed to investigate the effect of
      lavender essential oil on the sleep quality and anxiety level of patients in
      coronary ICU. PARTICIPANTS: A total of 60 patients in coronary ICU participated
      in this study. DESIGN: A randomized controlled study was conducted with 60
      patients in a province located in the southeast of Turkey. METHODS: After
      informing the patients in both groups about the study, they were administered a
      questionnaire, Pittsburgh Sleep Quality Index (PSQI) and the Beck Anxiety
      Inventory (BAI) scale. The patients in the intervention group were given 2%
      lavender essential oil via inhalation for 15 days after which they were
      administered the same scales again to evaluate the sleep quality and anxiety. As
      for the control group, they were administered the same scales again after 15 days
      without the inhalation of lavender essential oil. RESULTS: Comparison of the PSQI
      and BAI scores of the patients in the control and intervention groups before and
      after the intervention showed statistically significant differences in the change
      in favour of the intervention group (p < 0.05). CONCLUSION: Lavender essential
      oil increased quality of sleep and reduced level of anxiety in patients with
      coronary artery disease. RELEVANCE TO CLINICAL PRACTICE: As a non-invasive,
      cheap, easily applicable, cost-effective, independent nursing intervention and
      appropriate for cardiac patients, lavender essential oil could be applied in
      ICUs.

PMID- 26211736
TI  - Whole genome sequence of Pseudomonas aeruginosa F9676, an antagonistic bacterium
      isolated from rice seed.
AB  - Pseudomonas aeruginosa is a group of bacteria, which can be isolated from diverse
      ecological niches. P. aeruginosa strain F9676 was first isolated from a rice seed
      sample in 2003. It showed strong antagonism against several plant pathogens. In
      this study, whole genome sequencing was carried out. The total genome size of
      F9676 is 6368,008bp with 5586 coding genes (CDS), 67 tRNAs and 3 rRNAs. The
      genome sequence of F9676 may shed a light on antagonism P. aeruginosa. 

PMID- 26211737
TI  - Very high cell density perfusion of CHO cells anchored in a non-woven matrix
      based bioreactor.
AB  - Recombinant Chinese Hamster Ovary (CHO) cells producing IgG monoclonal antibody
      were cultivated in a novel perfusion culture system CellTank, integrating the
      bioreactor and the cell retention function. In this system, the cells were
      harbored in a non-woven polyester matrix perfused by the culture medium and
      immersed in a reservoir. Although adapted to suspension, the CHO cells stayed
      entrapped in the matrix. The cell-free medium was efficiently circulated from the
      reservoir into- and through the matrix by a centrifugal pump placed at the bottom
      of the bioreactor resulting in highly homogenous concentrations of the nutrients
      and metabolites in the whole system as confirmed by measurements from different
      sampling locations. A real-time biomass sensor using the dielectric properties of
      living cells was used to measure the cell density. The performances of the
      CellTank were studied in three perfusion runs. A very high cell density measured
      as 200 pF/cm (where 1 pF/cm is equivalent to 1 * 10(6)viable cells/mL) was
      achieved at a perfusion rate of 10 reactor volumes per day (RV/day) in the first
      run. In the second run, the effect of cell growth arrest by hypothermia at
      temperatures lowered gradually from 37  degrees C to 29  degrees C was studied
      during 13 days at cell densities above 100 pF/cm. Finally a production run was
      performed at high cell densities, where a temperature shift to 31  degrees C was
      applied at cell density 100 pF/cm during a production period of 14 days in
      minimized feeding conditions. The IgG concentrations were comparable in the
      matrix and in the harvest line in all the runs, indicating no retention of the
      product of interest. The cell specific productivity was comparable or higher than
      in Erlenmeyer flask batch culture. During the production run, the final harvested
      IgG production was 35 times higher in the CellTank compared to a repeated batch
      culture in the same vessel volume during the same time period.

PMID- 26211738
TI  - The circular RNA Cdr1as, via miR-7 and its targets, regulates insulin
      transcription and secretion in islet cells.
AB  - Among the identified thousands of circular RNAs (circRNA) in humans and animals,
      Cdr1as (also known as CiRS-7) was recently demonstrated to act as a powerful miR
      7 sponge/inhibitor in developing midbrain of zebrafish, suggesting a novel
      mechanism for regulating microRNA functions. MiR-7 is abundantly expressed in
      islet cells, but overexpressing miR-7 in transgenic mouse beta cells causes
      diabetes. Therefore, we infer that Cdr1as expression may inhibit miR-7 function
      in islet cells, which in turn improves insulin secretion. Here, we show the first
      characterization of Cdr1as expression in islet cells, which was upregulated by
      long-term forskolin and PMA stimulation, but not high glucose, indicating the
      involvement of cAMP and PKC pathways. Remarkably, both insulin content and
      secretion were significantly increased by overexpression of Cdr1as in islet
      cells. We further identified a new target Myrip in the Cdr1as/miR-7 pathway that
      regulates insulin granule secretion, and also another target Pax6 that enhances
      insulin transcription. Taken together, our findings revealed the effects of the
      strongly interacting pair of Cdr1as/miR-7 on insulin secretion, which may become
      a new target for improving beta cell function in diabetes. 

PMID- 26211739
TI  - Heart rate variability is reduced in underweight and overweight healthy adult
      women.
AB  - Heart rate variability (HRV) is altered in obese subjects, but whether this is
      true also in underweight (UW) subjects is still under debate. We investigated the
      HRV profile in a sample of healthy adult women and its association with
      adiposity. Five-minute resting state electrocardiographic activity was recorded
      in 69 subjects grouped according to their body mass index, [23 normal weight
      (NW), 23 overweight/obese (OW) and 23 UW). Body fat mass (FM) was measured by bio
      impedance. Frequency- and time-domain analyses were performed. Compared to NW, UW
      and OW subjects showed a significant decrease in HRV indices, as revealed by
      spectral analysis. No differences were observed between UW and OW subjects. A
      second-order polynomial regression unveiled an inverted U-shaped relationship
      between FM extent and HRV indices. A decrease of HRV indices was associated with
      changes in FM extent, proving that in UW and OW subjects, the adaptive
      flexibility of autonomic cardiac function was reduced. These findings provide
      important clues to guide future studies addressed to determine how changes in
      adiposity and autonomic cardiac function may contribute to health risk.

PMID- 26211740
TI  - Lymphatic transit rate as a novel predictive parameter for nodal metastasis in
      primary truncal skin cancers.
AB  - Prediction of nodal metastasis in skin cancer before sentinel lymph node (SLN)
      biopsies is ideal to avoid unnecessary SLN biopsy performance. Primary truncal
      skin cancers are characterized by the lymphatic flow that drains from the primary
      lesion, occasionally to plural nodal basins. The scintigraphic appearance time
      (SAT), defined as the time between radionuclide injection and first SLN
      visualization, can potentially predict nodal metastasis, and a short SAT is a
      predictive parameter for metastasis. We recently introduced a novel method to
      measure the lymphatic flow rate using dynamic lymphoscintigraphy exhibiting a
      time-activity curve in the SLN. The time at which the count reaches a plateau in
      the SLN is termed the scintigraphic saturation time (SST) and can be a good
      alternative to the SAT. Moreover, the value obtained by division of the distance
      between the primary lesion and the SLN by the SST was termed the lymphatic
      transit rate (LTR), which represents the scintigraphic saturation velocity. In
      the present study, we evaluated LTR as a predictive parameter for nodal
      metastasis. Data for 22 lymph nodes from 18 patients with primary truncal skin
      cancers were used. Histopathologically, nodal metastasis was determined in nine
      nodes of eight patients. Because the mean LTR were 1.84 cm/min in non-metastatic
      SLN and 2.38 cm/min in metastatic SLN, the LTR was significantly higher in
      metastatic SLN than in non-metastatic SLN. All SLN with LTR of less than 1.8
      cm/min were histopathologically evaluated as non-metastatic. The LTR may be a
      predictive indicator for nodal metastasis. 

PMID- 26211741
TI  - Toxicity of Hexamoll((r)) DINCH((r)) following intravenous administration.
AB  - Alternative plasticizers to di(2-ethylhexyl) phthalate (DEHP) for blood bags have
      been sought for many years. Cyclohexane-1,2-dicarboxylic acid, diisononylester
      (Hexamoll((r)) DINCH((r))) is an alternative that has been evaluated in
      preliminary studies for compatibility and efficacy to preserve whole blood. While
      Hexamoll((r)) DINCH((r)) has an extensive database for mammalian toxicity via
      oral administration, data were needed to evaluate toxicity from intravenous (IV)
      administration to support the use of the plasticizer Hexamoll((r)) DINCH((r)) in
      blood bags. A series of studies was performed by slow IV injection or IV infusion
      of Hexamoll((r)) DINCH((r)), a highly viscous, hydrophobic substance, suspended
      in Intralipid((r)) 20% (20% intravenous fat emulsion). Rats were injected once,
      followed by 14 days of recovery; injected daily for 5 days followed by 5 days of
      recovery, or infused for 29 days (4h/day) followed by 14 days of recovery. Dose
      levels were 0, 62, 125, and 250-300mg/kg body weight/day. These dose levels
      represent the limits of suspension and far exceed any anticipated exposures from
      migration out of plasticized blood bags. Animals were observed for signs of
      toxicity; body weight and feed consumption were measured; blood collected for
      clinical chemistry and hematology; and tissues collected and processed for
      histopathology. Special emphasis was placed on evaluating endpoints and tissues
      that are commonly associated with plasticizer exposure in rodents. Urine was
      collected during the 4-week study to quantify urinary metabolites of
      Hexamoll((r)) DINCH((r)). The results of the studies indicate that no substance
      related toxicity occurred: no effects on behavior, no effects on organ weight, no
      effect on serum chemistry including thyroid hormones; and no effect on major
      organs, especially no testicular toxicity and no indication for peroxisome
      proliferation in the liver. The only effects seen were petechia and granulomas
      related to dissipation of suspended Hexamoll((r)) DINCH((r)) in the aqueous
      environment of the blood. However, the results of metabolite analyses demonstrate
      that Hexamoll((r)) DINCH((r)) was bioavailable. Therefore, based on the lack of
      Hexamoll((r)) DINCH((r))-related systemic toxicity with the exception of the
      physical limitations, the no-observed-adverse-effect level for parenterally
      administered Hexamoll((r)) DINCH((r)) is considered to be 300mg/kg bw/day. 

PMID- 26211742
TI  - Increased risk of hepatocellular carcinoma in chronic hepatitis C patients with
      new onset diabetes: a nation-wide cohort study.
AB  - BACKGROUND: The impact of diabetes for hepatocellular carcinoma (HCC) development
      in chronic hepatitis C (CHC) patients remains controversial. AIM: To investigate
      the risk of HCC in CHC patients who develop new onset diabetes. METHODS: We
      conducted a nation-wide cohort study by using Taiwanese National Health Insurance
      Research Database, which comprised of data from >99% of entire population. Among
      randomly sampled one million enrollees, 6251 adult CHC patients were identified
      from 1997 to 2009. Diabetes was defined as new onset in the patient who was given
      the diagnosis in the years 1999-2009 but not in 1997-1998. The cohorts of CHC
      with new onset diabetes (n = 1100) and 1:1 ratio age-, gender-, and inception
      point (onset date of diabetes) matched nondiabetes (n = 1087) were followed up
      from the inception point until the development of HCC, withdrawal from insurance,
      or December 2009. RESULTS: After adjustment for competing mortality, patients
      with new onset diabetes had a significantly higher cumulative incidence of HCC
      (Relative Risk = 1.544, 95% CI = 1.000-2.387, modified log-rank test, P = 0.047)
      as compared to those without. After adjustment for age, gender, cirrhosis,
      hyperlipidaemia, CHC treatment, diabetes treatment, comorbidity index, obesity
      and statins therapy by Cox proportional hazard model, diabetes was still an
      independent predictor for HCC (hazard ratio (HR) = 1.906, 95% CI = 1.102-3.295, P
      = 0.021). The risk for HCC was increased in those who were 40-59 years old,
      independent of other variables (HR = 3.086, 95% CI = 1.045-9.112, P = 0.041), and
      after adjustment for competing mortality (modified log-rank test, P = 0.009).
      CONCLUSION: Chronic hepatitis C patients who develop diabetes are at an increased
      risk of hepatocellular carcinoma over time.

PMID- 26211744
TI  - 6,7-Bismethoxy-2,11-dihydroxytetraphenylene Derived Macrocycles: Synthesis,
      Structures, and Complexation with Fullerenes.
AB  - 6,7-Bismethoxy-2,11-dihydroxytetraphenylene (1), a novel building block of
      tetraphenylene-derived macrocycles, was synthesized via palladium-catalyzed cross
      coupling reactions and characterized by X-ray diffraction. The relevant
      macrocyclic hosts derived from 1 have well-defined structures with fixed
      conformations both in solution and solid state. They showed efficient and unique
      properties toward complexation with fullerenes C60 and C70 in toluene. 

PMID- 26211743
TI  - Downregulation of TBXAS1 in an iron-induced malignant mesothelioma model.
AB  - Malignant mesothelioma is an aggressive and therapy-resistant neoplasm arising
      from mesothelial cells. Evidence suggests that the major pathology associated
      with asbestos-induced mesothelioma is local iron overload. In the present study,
      we induced iron-induced mesothelioma in rats based on previous reports. Ten
      Wistar rats were given ferric saccharate and nitrilotriacetate i.p. for 5 days a
      week. Five of the ten rats exhibited widespread mesotheliomas in the peritoneum
      and tunica vaginalis. The tumor cells showed positive immunostaining for
      calretinin, wilms tumor-1, podoplanin and the oxidative DNA marker 8-hydroxy-2'
      deoxyguanosine. In three of the five rats with mesothelioma, array-based
      comparative genomic hybridization analysis identified a common chromosomal
      deletion mapped to the chromosomal 4q31 locus, which encompasses the TBXAS1 gene.
      Downregulation of the TBXAS1 gene was confirmed using quantitative PCR. TBXAS1
      gene expression was also reduced in three of four human malignant pleural
      mesothelioma cell lines compared with normal bronchial epithelial cells.
      Immunohistochemistry revealed that TBXAS1 expression was weakly positive and
      positive in five and three out of eight human malignant mesothelioma samples,
      respectively. In conclusion, TBXAS1 gene expression was downregulated in rats
      with iron-induced mesothelioma. The relationship between iron overload and TBXAS1
      downregulation should be pursued further. 

PMID- 26211745
TI  - Rattling in the Quadruple Perovskite CuCu3 V4 O12.
AB  - Of particular interest is a peculiar motion of guest atoms or ions confined to
      nanospace in cage compounds, called rattling. While rattling provides unexplored
      physical properties through the guest-host interactions, it has only been
      observed in a very limited class of materials. Herein, we introduce an A-site
      ordered quadruple perovskite, CuCu3 V4 O12 , as a new family of cage compounds.
      This novel AA'3 B4 O12 -type perovskite has been obtained by a high-pressure
      synthesis technique and structurally characterized to have cubic Im$?bar 3$
      symmetry with an ionic model of Cu(2+) Cu(2+) 3 V(4+) 4 O12 . The thermal
      displacement parameter of the A-site Cu(2+) ion is as large as Uiso ~0.045 A(2)
      at 300 K, indicating its large-amplitude thermal oscillations in the oversized
      icosahedral cages. Remarkably, the presence of localized phonon modes associated
      with rattling of the A-site Cu(2+) ion manifests itself in the low-temperature
      specific heat data. This work sheds new light on the structure-property relations
      in perovskites. 

PMID- 26211747
TI  - [Measurement of natriuretic peptides in heart failure: the good laboratory and
      clinical practice].
AB  - Cardiac natriuretic peptides (BNP, NT-proBNP) play a pivotal role in
      cardiovascular homeostasis, mainly due to their roles in vasodilatation,
      natriuresis, diuresis and due to their antiproliferative properties. Proper
      measurement of the natriuretic peptide levels may help differentiate between
      respiratory and cardiac forms of dyspnea, diagnose early forms of heart failure,
      evaluate severity of heart failure (prognosis) and monitor the efficacy of
      therapy. In many countries natriuretic peptide levels are being used as one of
      the earliest diagnostics tools to evaluate the involvement of the heart. Current
      theoretical and clinical data confirm the importance of natriuretic peptides in
      routine healthcare. These roles are clearly described in international
      recommendations and guidelines. In the current review the authors discuss the
      problems of the measurement of natriuretic peptides in Hungary, including several
      aspects related to laboratory medicine, cardiology and health economy.

PMID- 26211748
TI  - [Are there cardiovascular adverse effects of inhaled anticholinergics?].
AB  - The purpose of this review is to discuss the cardiovascular risk associated with
      inhaled anticholinergics in chronic obstructive pulmonary disease. Several meta
      analyses of data for tiotropium raised the possibility of an increased risk for
      arrhythmia, angina, myocardial infarction, etc. This review includes the data of
      retrospective studies of databases using databases, randomized controlled trials,
      and meta-analyses of clinical trials. The conclusions of studies were
      inconsistent. In most clinical trials the incidence of cardiovascular adverse
      events was similar in active treatment and placebo groups, especially in patients
      with previous cardiovascular diseases. Considering meta-analyses, there is
      little, if any, evidence for the association between anticholinergics and the
      development of cardiovascular symptoms. The author discusses the presence and
      function of cholinergic receptor subtypes in human heart, and cardiac functions
      controlled by the autonomic nervous system via these receptors, their possible
      role, and pharmacokinetic properties of inhaled anticholinergics. The author
      concludes that it is not possible to find evidence of increased cardiovascular
      harm of inhaled anticholinergics.

PMID- 26211749
TI  - [Satisfaction of parents raising children under 7 years of age with general
      practitioners in Hungary].
AB  - INTRODUCTION: Development of children's primary care may only take place through
      proper monitoring of both providers and recipients. AIM: The aim of the study was
      to investigate the parental satisfaction with the doctor of 0-7 years old
      children. METHOD: The research took place in Budapest and five Hungarian counties
      in "Early Childhood (0-7 years) Programme 6.1.4/12/1-2012-0001". There were 980
      parental questionnaires were evaluated and 93 parents participated in ten focus
      group interviews (n = 93). RESULTS: Answers indicated that parents were most
      satisfied with the information received from the physician of their child (score
      3.8), and they were least satisfied with the waiting time and the time of
      consulting hours (score 3.4). The results of focus group interviews were similar
      to those obtained from the questionnaire survey. CONCLUSIONS: Participating
      parents are "rather satisfied" or "satisfied" with the physician of their child.
      Evaluation of the results forms basis to create indicators for primary care
      improvement.

PMID- 26211746
TI  - Hdac3 Deficiency Increases Marrow Adiposity and Induces Lipid Storage and
      Glucocorticoid Metabolism in Osteochondroprogenitor Cells.
AB  - Bone loss and increased marrow adiposity are hallmarks of aging skeletons.
      Conditional deletion of histone deacetylase 3 (Hdac3) in murine
      osteochondroprogenitor cells causes osteopenia and increases marrow adiposity,
      even in young animals, but the origins of the increased adiposity are unclear. To
      explore this, bone marrow stromal cells (BMSCs) from Hdac3-depleted and control
      mice were cultured in osteogenic medium. Hdac3-deficient cultures accumulated
      lipid droplets in greater abundance than control cultures and expressed high
      levels of genes related to lipid storage (Fsp27/Cidec, Plin1) and glucocorticoid
      metabolism (Hsd11b1) despite normal levels of Ppargamma2. Approximately 5% of the
      lipid containing cells in the wild-type cultures expressed the master osteoblast
      transcription factor Runx2, but this population was threefold greater in the
      Hdac3-depleted cultures. Adenoviral expression of Hdac3 restored normal gene
      expression, indicating that Hdac3 controls glucocorticoid activation and lipid
      storage within osteoblast lineage cells. HDAC3 expression was reduced in bone
      cells from postmenopausal as compared to young women, and in osteoblasts from
      aged as compared to younger mice. Moreover, phosphorylation of S424 in Hdac3, a
      posttranslational mark necessary for deacetylase activity, was suppressed in
      osseous cells from old mice. Thus, concurrent declines in transcription and
      phosphorylation combine to suppress Hdac3 activity in aging bone, and reduced
      Hdac3 activity in osteochondroprogenitor cells contributes to increased marrow
      adiposity associated with aging. (c) 2015 American Society for Bone and Mineral
      Research. 

PMID- 26211750
TI  - [Investigation of metal element content of some European and Far Eastern herbs].
AB  - INTRODUCTION: Metal elements and their excess intake have significant influence
      on general health. AIM: There is only little information how Far Eastern herbs
      resemble European's regarding their purity and essential metal element content.
      The aim of the authors was to determine metal elements in different Chinese and
      European herbs and extracts. METHOD: The studied European herbs included
      Calendula officinalis petals, Achillea millefolium, Epilobium parviflorum herba,
      Urtica dioica leaves, Crataegus monogyna flowers while Far Eastern herbs were
      Cordyceps sinensis, Ganoderma lucidum, Ginkgo biloba leaves, Panax ginseng and
      Curcuma longa roots. The analysis was performed using inductively coupled plasma
      optical emission spectroscopy. RESULTS: There was no considerable difference in
      essential metal elements and the Ca:Mg concentration ratio between European and
      Far Eastern drugs and extracts. CONCLUSIONS: The extracts are preferential metal
      element sources and their magnesium content are also advantageous, because of a
      shift of the Ca:Mg concentration ratio towards magnesium.

PMID- 26211752
TI  - Treatment rate and factors related to interferon-based treatment initiation for
      chronic hepatitis C in South Korea.
AB  - Under-recognition and under-treatment of chronic hepatitis C virus (HCV)
      infection is an important determinant of the disease outcome. The aim of this
      study was to investigate the treatment rate and factor of initiation of
      interferon-based antiviral treatment for chronic hepatitis C patients in a
      prospective, multicenter Korean HCV cohort. Treatment-naive 759 patients with
      chronic HCV infection were prospectively followed from January 2007-2013 at six
      university hospitals during a median (interquartile range) follow-up of 769 (76
      1,427) days. The subjects consisted of patients with chronic hepatitis C (n =
      553, 72.9%), liver cirrhosis (n = 127, 16.7%), and hepatocellular carcinoma (n =
      79, 10.4%), and were treated usually using pegylated interferon alpha and
      ribavirin. Treatment initiation rate and its related factors were analysed. The
      initiation rate of antiviral treatment was 37.3% (n = 273), and the cumulative
      probability of treatment initiation over 5 years was 39.4%. Multivariate analysis
      showed that age <58 years (hazard ratio [HR] = 1.588, 95% CI = 1.151-2.193), job
      employment (HR = 1.737, 95% CI = 1.279-2.363), absence of HCC (chronic hepatitis,
      HR = 2.534, 95% CI = 1.003-6.400; liver cirrhosis, HR = 2.873, 95% CI = 1.101
      7.494), alanine transaminase (ALT) >40 IU/L (HR = 1.682, 95% CI = 1.228-2.303),
      and genotype 2 (HR = 1.364, 95% CI = 1.034-1.798) were independent factors
      related to treatment initiation. Interferon-based antiviral treatment was
      initiated in more than one third of chronic HCV infected patients visiting
      university hospitals, who were young, employed, HCV genotype 2, and with abnormal
      ALT without HCC, in Korea.

PMID- 26211753
TI  - Tacrolimus: an effective treatment in refractory psoriatic arthritis following
      biologic failure.

PMID- 26211754
TI  - Contrasting PCB bioaccumulation patterns among Lake Huron lake trout reflect
      basin-specific ecology.
AB  - This study collected multiple age classes of lake trout from Lake Huron's Main
      Basin, Georgian Bay, and North Channel regions to compare and contrast top
      predator polychlorinated biphenyl (PCB) bioaccumulation patterns in separate
      compartments of the same ecosystem. Sum PCB concentrations were highest for Main
      Basin (260 +/- 24.9 ng g(-1) wet wt) fish, followed by Georgian Bay (74.6 +/-
      16.2 ng g(-1) ) and North Channel (42.0 +/- 3.3 ng g(-1)) fish. Discriminant
      functions analysis of lake trout PCB profiles and stable carbon (delta(13)C) and
      nitrogen (delta(15)N) isotope values clearly distinguished fish by location,
      indicating high degrees of basin fidelity throughout their lifetimes in addition
      to highly contrasting PCB bioaccumulation profiles. These unique profiles were
      not attributable to significant differences in lake trout lipid contents (p =
      0.856) or trophic position (delta(15)N; p = 0.334), with rainbow smelt
      representing the primary prey across the basins. Furthermore, significant
      differences were observed among the basins for the relationships between PCB
      biomagnification factors and hydrophobicity. An empirical model for predicting
      PCB biomagnification in Lake Huron lake trout indicated that basin-specific
      population growth rates and prey abundances were significant for explaining these
      contrasting patterns of PCB bioaccumulation. The results of the present study are
      fundamental for understanding the role of ecology in legacy persistent organic
      pollutant (POP) bioaccumulation. Specifically, ecosystem characteristics such as
      prey abundances, foraging ecology, and ultimately consumer growth can regulate
      the variability of legacy POP bioaccumulation as observed within and among a wide
      range of freshwater ecosystems.

PMID- 26211755
TI  - Computer-aided design of T-cell epitope-based vaccines: addressing population
      coverage.
AB  - Epitope-based vaccines (EVs) make use of short antigen-derived peptides
      corresponding to immune epitopes, which are administered to trigger a protective
      humoral and/or cellular immune response. EVs potentially allow for precise
      control over the immune response activation by focusing on the most relevant -
      immunogenic and conserved - antigen regions. Experimental screening of large sets
      of peptides is time-consuming and costly; therefore, in silico methods that
      facilitate T-cell epitope mapping of protein antigens are paramount for EV
      development. The prediction of T-cell epitopes focuses on the peptide
      presentation process by proteins encoded by the major histocompatibility complex
      (MHC). Because different MHCs have different specificities and T-cell epitope
      repertoires, individuals are likely to respond to a different set of peptides
      from a given pathogen in genetically heterogeneous human populations. In
      addition, protective immune responses are only expected if T-cell epitopes are
      restricted by MHC proteins expressed at high frequencies in the target
      population. Therefore, without careful consideration of the specificity and
      prevalence of the MHC proteins, EVs could fail to adequately cover the target
      population. This article reviews state-of-the-art algorithms and computational
      tools to guide EV design through all the stages of the process: epitope
      prediction, epitope selection and vaccine assembly, while optimizing vaccine
      immunogenicity and coping with genetic variation in humans and pathogens. 

PMID- 26211756
TI  - Diphenyliodonium-Catalyzed Fluorination of Arynes: Synthesis of ortho
      Fluoroiodoarenes.
AB  - Described is a one-pot vicinal fluorination-iodination of arynes at room
      temperature. The diphenyliodonium salt proved to be a privileged catalyst for
      this nucleophilic fluorination process using CsF as a fluorine source, and a
      subsequent facile electrophilic iodination with C4 F9 I was also found to be
      crucial to ensure the efficient fluorination. This new synthetic protocol has a
      broad substrate scope under mild reaction conditions. 

PMID- 26211757
TI  - Bronsted Acid-Catalyzed Cascade Reactions Involving 1,2-Indole Migration.
AB  - A cascade reaction of indoles with propargylic diols involving an unprecedented
      metal-free 1,2-indole migration onto an alkyne was carried out. DFT calculations
      support a mechanism consisting of a concerted nucleophilic attack of the indole
      nucleus with loss of water, followed by the 1,2-migration and subsequent Nazarov
      cyclization. This Bronsted acid-catalyzed protocol affords indole-functionalized
      benzofulvene derivatives in high yields. 

PMID- 26211758
TI  - Necrotizing fasciitis: 11-year retrospective case review in South Auckland.
AB  - BACKGROUND: The aims of this paper were to review our experience with necrotizing
      fasciitis at Middlemore Hospital and to define the trends in incidence, inpatient
      mortality and microbiological profile. METHODS: A computerized search of the
      electronic medical records was undertaken to identify adult patients with a
      diagnosis of necrotizing fasciitis between January 2000 and December 2010. A
      retrospective review of the clinical records was performed. RESULTS: Of the 138
      patients with necrotizing fasciitis identified, 129 had their diagnosis confirmed
      at operation. The mortality at 30 days was 20.3% (95% confidence interval (CI)
      13.9%-28.0%). There was a significant reduction in hospital mortality in each
      successive year of the study period with an odds ratio of 0.84 (95% CI 0.71-0.98,
      P = 0.03). A pattern of increasing incidence was noted until February 2004 (95%
      CI September 2002-July 2005). This was followed by a significant decrease in
      incidence. The empirical antibiotic regime of clindamycin, gentamicin and
      penicillin provides satisfactory cover against 95% of the causative pathogens.
      CONCLUSION: This represents the largest single-centre published case series in
      New Zealand. Despite concerns of increasing incidence and mortality associated
      with necrotizing fasciitis in New Zealand, the experience in South Auckland shows
      a decrease in incidence of necrotizing fasciitis since 2004 and a statistically
      significant decreasing trend in hospital mortality.

PMID- 26211760
TI  - [Recent progress in the perioperative management in gastrointestinal surgery].
AB  - The last half century has witnessed a rapid progress in gastrointestinal surgery,
      and the development of minimally invasive technique has boosted gastrointestinal
      surgery into a new era. The concept of perioperative management becomes more
      comprehensive by the introduction of damage control surgery and early recovery
      after surgery(ERAS). One of the most prerequisite for successful operation is the
      correct diagnosis and accurate assessment and correction of malnutrition. A real
      mastery and proper selection of operative techniques and instruments based on the
      patients' preoperative condition could reduce tissue damage and postoperative
      complications. Postoperative analgesia facilitates early mobilization and
      recovery of patients, and may reduce posoperative cardiopulmonary complications.
      Early enteral feeding could promote recovery of gastrointestinal function,
      protect gastrointestinal barrier, prevent dysbiosis of gut flora, thus facilitate
      patients' recovery. 

PMID- 26211761
TI  - [Critical role of enhanced recovery after surgery during the perioperative
      management].
AB  - Perioperative management includes all the treatments during pre-, intra-, and
      post-operative periods. The enhanced recovery after surgery applies a series of
      evidence-based perioperative measures to accelerate patients' recovery by
      reducing both physical and mental stress caused by surgical operation. Compared
      with traditional perioperative management, it decreases the rate of complication
      and re-admission, and shortens the length of hospitalization without any impact
      on safety. The principle, strategy, and technique of enhanced recovery after
      surgery will be integrated into the perioperative management of all the patients
      in the future. 

PMID- 26211759
TI  - Environmental condition alters amphetamine self-administration: role of the
      MGluR5 receptor and schedule of reinforcement.
AB  - RATIONALE: Evidence suggests that differential rearing influences the function of
      a receptor subtype critical for maintaining glutamate homeostasis. Maintaining
      homeostatic glutamatergic function may be an important protector against drug
      abuse. OBJECTIVE: This study sought to determine if differential rearing
      influences the function of a receptor critical for glutamate homeostasis, which
      could in turn affect rates of amphetamine self-administration. METHODS: Rats were
      assigned to enriched (EC), isolated (IC), or standard (SC) conditions. After
      rearing for 30 days, rats were trained to lever press for sucrose reinforcement
      before the implantation of indwelling jugular catheters. After reaching stable
      responding for amphetamine (0.03 or 0.1 mg/kg/infusion), rats were injected with
      five doses (0, 0.3, 1.0, 3.0, and 5.0 mg/kg) of the mGluR5 antagonist, 3-((2
      methyl-1,3-thiazol-4-yl)ethynyl) pyridine hydrochloride (MTEP), 30 min before
      self-administration sessions. Following fixed-ratio (FR-1) testing, rats were
      administered identical doses of MTEP on a progressive-ratio (PR) reinforcement
      schedule. RESULTS: MTEP (3.0 mg/kg) attenuated FR-1 self-administration (0.03
      mg/kg/infusion) in IC rats. MTEP also dose-dependently attenuated amphetamine
      self-administration (0.1 mg/kg/infusion) during FR-1 and PR sessions, with 5.0
      mg/kg MTEP attenuating amphetamine self-administration in IC and SC rats and 3.0
      mg/kg MTEP attenuating amphetamine self-administration in EC and SC rats. PR
      results also revealed that IC rats not treated with MTEP were more motivated to
      self-administer the higher dose of amphetamine. CONCLUSIONS: These results
      suggest that the mGlu5 receptor mediates differences in drug-taking behavior
      among differentially reared rats. Isolation also decreased sensitivity to MTEP,
      suggesting that environmental factors alter glutamate homeostasis which
      subsequently affects sensitivity and motivation to self-administer amphetamine.

PMID- 26211762
TI  - [Perioperative nutrition support for gastrointestinal surgery].
AB  - Patients with gastrointestinal disease usually suffer from malnutrition, which is
      associated with poorer outcome, including longer length of stay, poorer wound
      healing, more infectious complications, reduced quality of life and higher
      mortality. Thus, acknowledgement of nutritional risk and nutritional risk factors
      are mandatory for nutritional therapy, to reduce risk of adverse complications
      and to improve clinical outcome. This article addresses and updates recent
      advances in clinical nutrition regarding gastrointestinal disease surgery and
      physiological considerations, essential for planning relevant nutritional therapy
      throughout the treatment course. 

PMID- 26211763
TI  - [Perioperative fluid management in gastrointestinal surgery].
AB  - Perioperative fluid management in gastrointestinal surgery is one of the key
      points to maintain sufficient blood perfusion and oxygen delivery for the organs,
      tissues and cells. Different strategies of fluid management have different
      influences on postoperative complications and mortality. After systematic review
      of related literature, we found that compared with the conventional liberal
      liquid administration, restricted liquid management and goal directed liquid
      management would benefit patients in general. With the guidance of cardiac output
      (CO), stroke volume (SV), stroke volume variation (SVV), pulse pressure variation
      (PPV) and pulse perfusion variation index (PVI), which can dynamically monitor
      the reactivity to volume, individualized goal-directed liquid management was more
      likely to maintain the perioperative hemodynamic stability, guarantee adequate
      tissue and organ blood perfusion and oxygen delivery, reduce perioperative
      complications, and shorten the postoperative hospital stay. In addition, the
      potential risk of tissue hypoperfusion caused by restricted liquid management
      should draw the clinicians' attention. More researches are needed to explore the
      right timing, the appropriate type of liquid and the reasonable amount of liquid
      to maintain the best functional state of tissues and organs perioperatively. 

PMID- 26211764
TI  - [Risk factors of surgical site infection in definitive surgery of intestinal
      fistulas].
AB  - OBJECTIVE: To investigate the risk factors of surgical site infection (SSI) in
      definitive surgery of intestinal fistulas. METHODS: Patients with
      gastrointestinal fistula undergoing definitive operation during November 2011 to
      November 2013 in Jinling Hospital were prospectively enrolled in the study. Risk
      factors of SSI were analyzed. Patients' characteristics, surgery-related data and
      fistula-related data were prospectively collected. Risk factors of SSI were
      analyzed. RESULTS: A total of 191 cases were enrolled and 51 cases developed SSI.
      Univariate analysis showed that patients with risk index category (RIC)>=2,
      length of abdominal incisions>15 cm, and duration of drainage tubes>10 days had
      significantly higher incidence of SSI (P<0.05). Multivariate Logistics analysis
      demonstrated that RIC and duration of drainage tube were independent risk factors
      for SSI (P=0.02, P=0.01, respectively). CONCLUSIONS: RIC>=2 and duration of
      drainage tubes>10 days are independent risk factors for development of SSI.

PMID- 26211765
TI  - [Effects of omega-3 polyunsaturated fatty acids on postoperative inflammatory
      reaction and clinical efficacy].
AB  - OBJECTIVE: To investigate the effect of omega-3 polyunsaturated fatty acids
      (PUFA) on postoperative inflammatory response and clinical efficacy in gastric
      cancer patients with nutritional risk. METHODS: All patients with gastric cancer
      in our department from June 2013 to January 2014 undergoing radical gastrectomy
      were prospectively enrolled in the study. Patients who matched the selection
      criteria were randomly divided into two groups: trial group (with omega-3 PUFA in
      parenteral nutrition) and control group (without omega-3 PUFA in parenteral
      nutrition). Levels of inflammatory factors (serum CRP, TNF-alpha, IL-1, IL-6, IL
      10) and nutrition-related proteins (prealbumin, retinol conjugated protein and
      transferrin) were compared between the two groups before operation and 2, 4 and 6
      days after operation. Incidence of postoperative systemic inflammatory response
      syndrome (SIRS) and other indicators associated with efficacy were compared
      between the two groups as well. RESULTS: Forty-seven patients were finally
      included in this study with 21 patients in the trial group and other 26 in the
      control group. There were no significant differences of inflammatory factors and
      nutrition-related proteins between the two groups before operation (all P>0.05).
      In the 6th days after operation, the levels of proinflammatory cytokines,
      including CRP, IL-1 and IL-6 were significantly lower in the trial group as
      compared to the control group, while the level of IL-10 (inhibiting inflammatory
      cytokine) was higher in the trial group, as well as levels of nutrition
      proteins(all P<0.05). The trial group had significantly lower rate of SIRS than
      the control group [57.1%(12/21) vs. 84.6% (22/26), P=0.036]. Compared with the
      control group, patients in the trial group had shorter bowel sound recovery time
      [(12.3+/-1.1) d vs. (3.1+/-1.3) d, P=0.025], earlier passage of flatus [(3.1+/
      1.0) d vs. (3.9+/-1.2) d, P=0.025] and shorter hospital stay [(9.4+/-2.1) d vs.
      (10.9+/-2.5) d, P=0.038], but there was no difference in postoperative
      complication rate between the two groups (P=0.678). CONCLUSIONS: Omega-3 PUFA can
      reduce the release of inflammatory promoters, promote the release of inhibiting
      inflammatory cytokine IL-10, decrease the incidence of SIRS, improve patients'
      nutritional state, expedite the recovery of gastrointestinal function and shorten
      patients' recovery time.

PMID- 26211766
TI  - [Complications associated with closure of defunctioning loop ileostomy in low
      anterior resection of rectal cancer].
AB  - OBJECTIVE: To analyze the complications of ileostomy closure and related risk
      factors. METHODS: Patients undergoing ileostomy closure in the Department of
      Colorectal Surgery, Peking University Cancer Hospital from September 2006 to
      March 2013 were included in this study. Clinical features of these patients were
      reviewed, the complications rate was calculated, and univariate and multivariate
      analyses with regard to the risk factors of surgical site infection(SSI) were
      also conducted. RESULTS: A total of 245 consecutive patients were enrolled in the
      study. Thirty-nine complications were observed in thirty-three patients, the
      overall complication rate was 13.5%. Complication after primary closure of
      defunctioning ileostomy included surgical site infection (n=21, 8.6%), ileus
      (n=8, 3.3%), preoperatively undiagnosed anastomotic leakage or rectovaginal
      fistula (n=5, 2.0%), pulmonary infection (n=2, 0.8%), and anal sphincter
      dysfunction (n=2, 0.8%). No patient died in the perioperative period, and 5
      patients (2.0%) underwent reoperation for ileus (n=3), anastomotic leakage (n=1)
      and rectovaginal fistula (n=1). Multivariate analysis showed that postoperative
      complications [OR=10.576, 95%CI:2.898-38.597, P=0.000] and total operation
      time>90 min[OR=4.862, 95% CI:1.758-13.451, P=0.002] were independent risk factors
      of SSI, and the presence of subcutaneous vacuum drainage [OR=0.063, 95%CI:0.007
      0.540, P=0.012] was protective factor of SSI. CONCLUSIONS: Surgical site
      infection is the most common complication after primary closure of defunctioning
      ileostomy. Subcutaneous vacuum drainage is effective for reducing SSI in patients
      undergoing primary closure of ileostomy, and it is especially recommended for
      patients with operation time>90 min.

PMID- 26211767
TI  - [Endoscopic covered self-expandable metal stents implantation in the management
      of anastomotic leakage after colorectal cancer surgery].
AB  - OBJECTIVE: To evaluate the efficacy and safety of covered self-expanding metallic
      stents (CSEMS) implantation as a treatment option in patients with anastomotic
      leakages after colorectal cancer surgery. METHODS: Short-term outcomes of 12
      patients with anastomotic leakage after colorectal cancer surgery undergoing
      CSEMS implantation between May 2013 and November 2014 were analyzed
      retrospectively. RESULTS: The mean time to diagnosis of anastomotic leakage was
      6.3 days (range 2-13). The median time of CSEMS implantation after anastomotic
      leakage was 8 days (range 2-55). Clinical success without reoperation was
      achieved in 10 of 12 cases (83.3%) and there was no mortality. The median time to
      healing of the anastomotic leakage after CSEMS implantation was 13 days (range 10
      33). The complications were stent migration (66.7%, 8/12), anorectal pain (58.3%,
      7/12), fecal incontinence (25.0%, 3/12) and enterocolic fistula (8.3%, 1/12).
      CONCLUSION: Stent implantation one week after relief of peritonitis of
      postoperative colorectal anastomotic leakages, combined with other conservative
      therapy (early indwelling of transanal double catheterization cannula and pelvic
      double catheterization cannula with persistent bathe and negative pressure
      aspiration) in the management of patients with early diagnosed anastomotic
      leakages is safe and effective.

PMID- 26211768
TI  - [Application of small intestine double stoma and succus entericus reinfusion in
      the patients with severe intra-abdominal infection].
AB  - OBJECTIVE: To evaluate the application of small intestine double stoma and succus
      entericus reinfusion in the patients with severe intra-abdominal infection.
      METHODS: Ten patients with high intestinal perforation from February 2005 to
      November 2014 were enrolled in the study. All the cases received emergency
      operation. Small bowel with intestinal perforation was resected, and double stoma
      was applied in the proximal and distal small intestine. When abdominal infection
      under control, total enteral nutrition was successfully administered from
      nasogastric tube. The succus entericus from the proximal intestine was collected
      and transfused back to the distal intestine. Stool was collected and fecal
      nitrogen, fat and carbohydrate contents were determined. Related serum protein
      levels were measured. RESULTS: As compared to pre-reinfusion, the absorption rate
      of carbohydrate [(90.9+/-7.8)% vs. (82.7+/-15.2)%], fat [(87.6+/-6.4)% vs.
      (59.1+/-10.8)%], and nitrogen [(82.4+/-9.8)% vs. (67.2+/-15.4)%] increased after
      succus entericus reinfusion (P<0.05). The serum protein levels increased
      significantly as well[fibronectin: (285.6+/-3.6) vs. (157.0+/-22.6) mg/L, P<0.01;
      transferrin: (4.86+/-0.21) vs. (3.60+/-0.25) g/L, P<0.05; pre-albumin: (291.3+/
      112.5) vs. (199.1+/-53.3) mg/L, P<0.05]. CONCLUSION: Small intestine double stoma
      and succus entericus reinfusion are effective in improving the absorption of
      carbohydrate, fat and nitrogen in the patients with severe intra-abdominal
      infection.

PMID- 26211769
TI  - [Effect of perioperative goal-directed fluid therapy on clinical outcome in
      elective colorectal resection].
AB  - OBJECTIVE: To assess the effect of perioperative goal-directed fluid therapy
      (GDFT) on clinical outcomes in elective colorectal resection. METHODS: A total of
      42 patients undergoing elective colorectal resection between March 2013 and
      December 2014 were recruited prospectively. GDFT was administrated based on
      corrected left ventricular ejection time and stroke volume using the esophageal
      Doppler monitoring. These patients were compared with a historical cohort of 58
      patients managed without GDFT from January 2012 to February 2013. The primary
      endpoint was postoperative hospital stay and complication rate. RESULTS: There
      was no significant difference in the overall fluid volumes administered
      intraoperatively between two groups [(2657+/-1037) ml vs. (2846+/-1444) ml,
      P>0.05], but patients in GDFT group received higher volume of colloid fluids
      [(935+/-556) ml vs. (688+/-414) ml, P<0.05]. After a period of concordance at the
      start of operation, corrected left ventricular ejection time, stroke volume and
      cardiac index increased in GDFT group compared with control group (all P<0.05).
      No significant differences were found in postoperative hospital stay [(11.27+/
      6.42) d vs. (12.04+/-7.18) d, P>0.05] and total complication rate (26.5% vs.
      25.9%, P>0.05) between two groups, but GDFT group had earlier postoperative
      flatus [(3.52+/-0.84) d vs. (4.48+/-0.71) d, P<0.05] and faster tolerated diet
      [(5.92+/-1.18) d vs. (6.83+/-0.95) d, P<0.05]. CONCLUSIONS: Patients undergoing
      elective colorectal resection do not benefit from intraoperative GDFT. Further
      studies should be carried out to investigate whether GDFT can be routinely used
      during colorectal resection.

PMID- 26211770
TI  - [Application of enteral nutrition in pediatric surgery].
AB  - OBJECTIVE: To explore the value and safety of the application of enteral
      nutrition in pediatric surgery. METHODS: Clinical data of 56 children patients
      who could not undertake oral feeding or those who required enteral nutrition by
      nasojejunal tube over 7 days in our ward from June 2007 to May 2013 were
      retrospectively analyzed. Children younger than one year old received enteral
      nutritional formulation Ai Er Shu mainly composed of short peptides or amino
      acids, and children over one year received Small peptide or Nengquansu mainly
      composed of short peptide. RESULTS: Among these 56 children patients, primary
      disease was pancreatitis in 20 cases, lacerated wound in 10, duodenal perforation
      in 6, duodenal septum-shape stenosis in 9, annular pancreas in 6, and
      hepatoblastoma in 5. All the patients successfully completed the enteral
      nutrition therapy within 7-37 (18+/-9.9) days with good recovery. During the
      treatment, 5 cases (8.9%) developed diarrhea, 3 cases (5.4%) nausea and vomiting,
      2 cases (3.6%) mild abdominal distension, 5 cases(8.9%) mild abdominal pain, and
      the symptoms were relieved after adjustment of nutrient solution concentration
      and infusion rate. After enteral nutrition for 10 days, the nutritional status of
      children was improved, and weight, blood red cell count, hemoglobin, serum
      albumin, prealbumin increased significantly (P<0.05). CONCLUSION: Application of
      enteral nutrition in pediatric surgery is safe and effective, which can improve
      the nutritional status of children and promote the recovery.

PMID- 26211771
TI  - [Effect of hepatitis on surgical treatment and prognosis of colorectal liver
      metastasis].
AB  - OBJECTIVE: To evaluate the effect of hepatitis on surgical treatment and
      prognosis of colorectal liver metastasis(CRLM). METHODS: A retrospective study of
      medical records of all the patients undergoing operation with colorectal liver
      metastasis in Peking University Hepatobiliary pancreatic Surgery Ward I from
      November 2007 to January 2013 was conducted. A total of 175 patients were
      eligible and divided into two groups: with hepatitis (n=16) or without hepatitis
      (n=159). RESULTS: Preoperative liver function was similar in these two groups.
      There were no significant differences in preoperative serum albumin, total
      bilirubin and prothrombin time between two groups (all P>0.05), except for lower
      blood platelet in hepatitis group after operation. Major hepatectomy was
      performed in 37.5% (6/16) and 22.0% (15/159) of two groups respectively (P>0.05).
      There were also no significant differences in operation time, blood loss,
      surgical complications and drainage volume (all P>0.05). The median overall
      survival time was 46 months in hepatitis group and 33 months in non-hepatitis
      group, and the median disease free time was 8 months in hepatitis group and 10
      months in non-hepatitis group (all P>0.05). CONCLUSION: CRLM patients concomitant
      with hepatitis have adequate liver reserve function for major hepatic resection
      and have similar prognosis of patients without hepatitis.

PMID- 26211772
TI  - [Influence of non-diabetic hyperglycemia on postoperative complications following
      laparoscopic colorectal cancer resection].
AB  - OBJECTIVE: To investigate the influence of non-diabetic hyperglycemia on
      postoperative complications following laparoscopic colorectal cancer resection.
      METHODS: Clinical data of 636 patients undergoing laparoscopic colorectal cancer
      resection in The Affiliated Nanhai Hospital of Southern Medical University
      between 2009 and 2013 were analyzed retrospectively. After excluding cases with
      diabetes mellitus, the patients were divided into the hyperglycemia group (blood
      glucose level>7.8 mmol/L at any time during hospitalization period, n=161) and
      the non-hyperglycemia group (n=309). RESULTS: Compared to non-hyperglycemia
      group, hyperglycemia group had more intraoperative blood loss [(186+/-80) ml vs.
      (158+/-74) ml, P=0.007] and longer postoperative hospital stay [(14.0+/-6.8) d
      vs. (11.2+/-5.5) d, P=0.013]. The overall rate of postoperative complication was
      24.8% and 16.5% respectively (P=0.030), in the hyperglycemia and the non
      hyperglycemia groups, and the mortality was 1.2% and 0.6% respectively (P=0.541).
      Multivariable analysis showed hyperglycemia was an independent risk factor of
      postoperative complication (RR=2.425, 95% CI:1.210-4.226, P=0.006). CONCLUSIONS:
      Non-diabetic hyperglycemia may increase the risk of postoperative complications
      following laparoscopic colorectal cancer resection. Perioperative blood glucose
      monitoring should be performed, regardless of patients with or without diabetes.

PMID- 26211773
TI  - [Radical effect and postoperative anal function of total mesorectum excision
      combined with different intersphincter resection in treatment of T1 and T2 stage
      ultra-low rectal cancer].
AB  - OBJECTIVE: To evaluate the radical effect and postoperative anal function of
      total mesorectum excision (TME) combined with different intersphincter resection
      (ISR) in treatment of T1 and T2 stage ultra-low rectal cancer. METHODS: Clinical
      data of 102 T1 and T2 stage ultra-low colorectal cancer patients who received TME
      combined with different ISR from January 2004 to December 2013 in our department,
      including 33 cases of complete internal anal sphincter excision ISR (complete ISR
      group), 39 cases of partial internal anal sphincter excision ISR (partial ISR),
      30 cases of partial dentate line reservation ISR (dentate line group). All the
      operation procedures followed the principles of TME. Radical conditions were
      compared and similarly, postoperative anal function was evaluated by Williams
      classification standard among 3 groups. RESULTS: The general information, such as
      gender, age, BMI, maximum diameter of tumor, distance of tumor edge to dentate
      line, TNM staging, degree of differentiation among 3 groups had no statistically
      significant differences (all P>0.05). The operation time, intraoperative blood
      loss, length of removed intestinal canal, resection margin, the harvested number
      of lymph nodes, and postoperative complications among 3 groups also had no
      statistically significant differences (all P>0.05). Twelve months after surgery,
      good anal function rate in part ISR group and dentate line group was 100%,
      significantly better than that in complete ISR group (75.8%) with significant
      difference (chi2=4.654, P=0.015). CONCLUSION: TME combined with ISR surgery in
      treatment of T1 and T2 stage ultra-low rectal cancer is safe and effective,
      which, as far as possible to preserve partial internal sphincter and dentate line
      on the premise of the guarantee of radical condition, can help to improve the
      postoperative anal function.

PMID- 26211774
TI  - [Effects of different gracilis loops in graciloplasty on congenital fecal
      incontinence].
AB  - OBJECTIVE: To compare the clinical effect of graciloplasty using two different
      gracilis encircled loops and to research the better method for the treatment of
      fecal incontinence after anoplasty for imperforate anus. METHODS: Clinical data
      of 38 incontinence patients with congenital anal malformation undergoing
      graciloplasty in our hospitals from January 2009 to January 2012 were
      retrospectively analyzed. Twenty patients received the modified surgery in which
      the gracilis muscle was transposed anticlockwise into a circum-anal tunnel with a
      U-loop and its tendon secured to the ipsilateral pectineal ligament. Eighteen
      patients received the traditional surgery in which the gracilis muscle was
      wrapped clockwise around the anus with a gamma-loop and its tendon secured to the
      contralateral periosteum of ischial tuberosity or pectineal ligament. All the
      patients were evaluated via Wexner score and anal manometry before surgery and 2
      weeks, 6 months, 1 year and 2 years after surgery. In addition, it was assessed
      whether the patients had difficulty defecating while squatting after surgery.
      RESULTS: Generalized estimating equations showed that the Wexner score in two
      groups gradually decreased after surgery (P=0.000), but there was no significant
      difference between two groups (P=0.554). At 2 weeks, 6 months, 1 year and 2 years
      after surgery, there were respectively 4 cases (20.0%), 3 cases (15.0%), 2 cases
      (10.0%), 1 case (5.0%), who showed squatting difficult defecation in the U-loop
      group, and 10 cases (55.6%), 12 cases (66.7%), 10 cases (55.6%), 8 cases (44.4%)
      in the gamma-loop group. The probability of squatting difficult defecation in U
      loop group was significantly lower compared to gamma-loop group (P=0.002), but
      the probability of squatting difficult defecation in two groups did not obviously
      change with time (P=0.057). Repeated measures ANOVA showed that anal resting
      pressure, anal maximal squeeze pressure, duration of anal squeeze, and rectal
      maximum tolerable volume in two groups were gradually improved after surgery (all
      P<0.01), but there were no significant differences between two groups (all
      P>0.05). CONCLUSIONS: Graciloplasty with different gracilis loops can improve
      anal function. However, U-loop can better improve difficult defecating while
      squatting, and is worthwhile for spreading in clinical practice.

PMID- 26211775
TI  - [Clinical presentation and risk factors for surgery in Crohn's disease].
AB  - OBJECTIVE: To investigate the risk factors on initial surgery in Crohn's disease.
      METHODS: The clinical data of 173 patients with Crohn's disease who were treated
      during 2010 and 2014 years in the Second Affiliated Hospital of Sun Yat-Sen
      University, were analyzed retrospectively. The patients who had received
      intestinal resection or whose initial symptoms occurred at least 5 years at the
      end of the follow-up were recruited. Montreal classification was used to evaluate
      lesion location and disease behavior. The risk factors of the initial surgery
      were analyzed by using Logistic regression model. RESULTS: Eighty-five patients
      (49.1%) received intestinal resection in 5 years after the onset of symptoms. The
      result of univariate analysis showed that the probability of surgical treatment
      is high in patients who were male and those older than 40 years at diagnosis
      (P<0.05). Lesions involving upper digestive tract, stenosis and penetrating
      lesions were also the risk factors on initial surgery in Crohn's disease
      (P<0.05). The result of multivariate analysis showed the relative risk of initial
      surgery was increased in male gender (OR=2.02, 95%CI:1.04-3.92) and in those who
      were older than 40 years at diagnosis (OR=2.34,95%CI:1.05-5.22). However, in
      patients with Crohn's disease involving colon alone, the relative risk of initial
      surgery was decreased (OR=0.35, 95%CI:0.13-0.97). CONCLUSION: Abdominal pain is
      the most common clinical presentation in Crohn's disease. Disease behavior and
      operation is closely related. Older than 40 years at diagnosis and male gender is
      high risk factor for surgery while colonic lesion alone is protective factor.

PMID- 26211776
TI  - [Effect of fish oil on intestinal Paneth cells in mouse with abdominal
      infection].
AB  - OBJECTIVE: To investigate the effect of fish oil on intestinal Paneth cells in
      mouse with abdominal infection. METHODS: Fifty C57BL/6J mouse were randomly
      divided into five groups (n=10 each): control group, sham group, infection group
      (cecal ligation and puncture, CLP), fish oil group (0.4 g/kg fish oil,
      intragastric administration every day, FO) and long chain triglyceride group (0.4
      g/kg soybean oil, intragastric administration every day, LCT). The mouse were
      sacrificed and the terminal ileum was collected for lysozyme, cryptdin 4 and
      secreted phosphatidase A2 (sPLA2) analysis at the fourth day after operation. The
      changes of mouse body weight and intestinal mucosa pathology were observed.
      RESULTS: The body weight, the mRNA levels of lysozyme, cryptdin 4 and sPLA2 and
      the protein level of lysozyme of Paneth cells in the infection group were reduced
      compared with the control group (0.78+/-0.34 vs. 1.83+/-0.11, 0.99+/-0.44 vs.
      2.02+/-0.33, 0.92+/-0.25 vs. 1.50+/-0.27, 0.31+/-0.06 vs. 0.45+/-0.05, all
      P<0.05), meanwhile the intestinal villi collapse and breakage occurred obviously.
      Fish oil could up-regulate the mRNA and protein expression of lysozyme (1.23+/
      0.27 vs. 0.78+/-0.34 and 0.62+/-0.23, 0.38+/-0.07 vs. 0.31+/-0.06 and 0.32+/
      0.06, all P<0.05) and alleviate the mucosa injury compared with the infection
      group and LCT group. CONCLUSIONS: The function of intestinal Paneth cells is
      damaged apparently after cecal ligation and puncture. Fish oil can relieve this
      injury.

PMID- 26211777
TI  - [Relationship of Ghrelin gene polymorphism with congenital anorectal malformation
      and Hirschsprung disease].
AB  - OBJECTIVE: To explore the relationship of Ghrelin gene polymorphism with the
      occurrence of human anorectal malformations (ARMs) and Hirschsprung
      disease(HSCR). METHODS: PCR and DNA sequencing were used to detect the single
      nucleotide polymorphism (SNPs) of 3 loci (rs139684563, rs149447194, rs186599567)
      genotype of Ghrelin gene in 100 children with ARMs, 100 children with HSCR, and
      100 healthy children (normal group). Genovariation and gene mutation were
      analyzed with case-control method. RESULTS: Three loci SNPs were in accordance
      with Hardy-Weinberg genetic equilibrium. No significant differences were found in
      rs139684563 allele and genotype frequencies between the cases and the normal
      groups (P>0.05). The allele and genotype frequencies of rs149447194 and
      rs186599567 were significantly different between cases and normal group (P<0.05).
      DNA sequencing results showed that wild-type homozygous deletion (176th and 191th
      base A deletion, respectively) were found in rs149447194 and rs186599567of ARMs
      and HSCR children, and single base substitution was detected in rs149447194 of
      ARMs children (194th codon nucleotide CCT to CTC). CONCLUSIONS: The rs149447194
      and the rs186599567 polymorphism changes may be associated with the pathogenesis
      of ARMs and HSCR.

PMID- 26211778
TI  - [Expression of TMEM16A in the colon of intractable functional constipation
      patients and its clinical implications].
AB  - OBJECTIVE: To investigate the expression of TMEMl6A in the colon of intractable
      functional constipation patients and its clinical implications. METHODS: A total
      of 30 patients with intractable chronic functional constipation were selected as
      trial group (full thickness tissue of sigmoid colon), 30 patients with colon
      cancer as control group (distant tissues at least 5 cm away from cancer). Tissues
      from two groups were collected in our hospital from February 2012 to June 2014
      and confirmed by pathological diagnosis. Immunofluorescence staining, RT-PCR and
      Western blot were performed to detect the mRNA and protein expression of TMEM16A
      and c-kit in colon. RESULTS: TMEM16A and c-kit protein expressions were observed
      in similar sites of colon tissues in two groups. Expressions of TMEM16A and C-kit
      in colon tissues detected by immunofluorescence, RT-PCR, and Western blotting
      were significantly lower in trial group than those in control group (TMEM16A:
      mean A 1.84+/-0.25 vs. 3.65+/-0.32, P<0.05, gray intensity ratio 0.66+/-0.07 vs.
      1.04+/-0.17, P<0.05, relative mRNA 0.41+/-0.05 vs. 1.00, P<0.05; c-kit: mean A
      3.38+/-0.24 vs. 5.06+/-0.31, gray intensity ratio 0.64+/-0.06 vs. 0.98+/-0.09,
      relative mRNA 0.18+/-0.08 vs. 1.00, all P<0.05). CONCLUSIONS: TMEM16A expression
      in colon tissues of intractable functional constipation patients is significantly
      lower and may adjust the movement of colonic smooth muscle by regulating the c
      kit expression. TMEMl6A may be used as a new candidate target for diagnosis and
      treatment of intractable functional constipation.

PMID- 26211779
TI  - [MicroRNA-146a polymorphism and susceptibility to gastrointestinal cancer: a meta
      analysis].
AB  - OBJECTIVE: To investigate the association between microRNA (miR)-146a gene
      polymorphisms and susceptibility to gastrointestinal cancer. METHODS: PubMed,
      Medline and Ovid full text databases, China Journal Full-text Database (CNKI),
      Articles Database and Chinese Biomedical Literature Database were researched to
      retrieved literatures about the association between miR-146a gene polymorphism
      and susceptibility to gastrointestinal cancer published from July 2010 to March
      2014. Modified Jadad quality score was used to evaluate the quality of the
      literatures and Stata 11.0 software was used to analyze and calculate OR value of
      the following 5 different genotypes: allele (G vs. C), the dominant genetic model
      (GC+GG vs. CC), a recessive genetic model (GG vs. GC+CC) and homozygote (GG vs.
      CC) and heterozygote (GC vs. CC) to assess the association. RESULTS: A total of
      16 studies were enrolled, including 7090 cancer patients and 9928 healthy
      controls. Meta-analysis showed that people with G allele was more susceptible to
      gastrointestinal cancer than those with C(gastric cancer: OR=1.1,95% CI:1.04
      1.17, P=0.001, colorectal cancer: OR=1.09,95% CI:1.01-1.18, P=0.020); dominant
      model (GC+GG) was more susceptible to gastric cancer than CC (OR=1.12, 95%
      CI:1.02-1.22, P=0.016); recessive genetic model GG was more susceptible to
      gastrointestinal cancer than CC+GC (gastric cancer: OR=1.16, 95% CI:1.05-1.27,
      P=0.004, colorectal cancer: OR=1.13, 95%CI:1.00-1.28, P=0.047); GG homozygote was
      more susceptible to gastrointestinal cancer than CC (gastric cancer: OR=1.20, 95%
      CI:1.06-1.35, P=0.003, colorectal cancer: OR=1.19, 95% CI:1.01-1.41, P=0.042).
      Dominant genetic model GC+GG and CC in colorectal cancer as well as heterozygous
      GC and CC in gastrointestinal cancer were not significantly different(P>0.05).
      CONCLUSION: miR-146a cancer susceptibility gene polymorphism is closely
      associated with gastrointestinal cancers.

PMID- 26211780
TI  - [Research progress of fecal microbiota transplantation].
AB  - Intestinal microbial ecosystem is the most complex and the largest micro
      ecosystem of the mammals. The use of antibiotics can lead to a lot of major
      changes of the flora, making the intestinal flora damaged and impacted, even
      developing Clostridium difficile infection. Fecal microbiota transplantation
      (FMT) as a special organ transplant therapy, which can rebuild the intestinal
      flora, has raised the clinical concerns. It has been used in the refractory
      Clostridium difficile, inflammatory bowel disease, irritable bowel syndrome,
      chronic fatigue syndrome, and some non-intestinal diseases related to the
      metabolic disorders. But this method of treatment has not become a normal
      treatment, and many clinicians and patients can not accept it. This paper reviews
      relevant literature in terms of origin, indications, mechanism, production
      process, current situation and future research, and provide a reference for the
      clinical application of the treatment of fecal microbiota transplantation. 

PMID- 26211781
TI  - Assessing coughing-induced influenza droplet transmission and implications for
      infection risk control.
AB  - Indoor transmission of respiratory droplets bearing influenza within humans poses
      high risks to respiratory function deterioration and death. Therefore, we aimed
      to develop a framework for quantifying the influenza infection risk based on the
      relationships between inhaled/exhaled respiratory droplets and airborne
      transmission dynamics in a ventilated airspace. An experiment was conducted to
      measure the size distribution of influenza-containing droplets produced by
      coughing for a better understanding of potential influenza spread. Here we
      integrated influenza population transmission dynamics, a human respiratory tract
      model, and a control measure approach to examine the indoor environment-virus
      host interactions. A probabilistic risk model was implemented to assess size
      specific infection risk for potentially transmissible influenza droplets indoors.
      Our results found that there was a 50% probability of the basic reproduction
      number (R0) exceeding 1 for small-size influenza droplets of 0.3-0.4 um,
      implicating a potentially high indoor infection risk to humans. However, a
      combination of public health interventions with enhanced ventilation could
      substantially contain indoor influenza infection. Moreover, the present dynamic
      simulation and control measure assessment provide insights into why indoor
      transmissible influenza droplet-induced infection is occurring not only in upper
      lung regions but also in the lower respiratory tract, not normally considered at
      infection risk.

PMID- 26211783
TI  - Embracing synthetic lethality of novel anticancer therapies.
AB  - INTRODUCTION: The significant challenge posed by cancer to human healthcare has
      led to the exploration of new approaches to combat it. Synthetic lethality (SL)
      is one such emerging area in the development of novel anticancer therapies. SL
      can be described as lethality (cell death) resulting from the combination of the
      two mutations, wherein the mutation in either of the two codependent genes in
      normal or cancer cells is viable. This concept is specifically being exploited in
      cancer research for selectively targeting specific tumor cells. AREAS COVERED: In
      this review, the authors summarize studies of SL-based novel anticancer
      therapies. The review highlights some of the selected advances in DNA damage
      response pathway-related SL pairs, particularly poly (ADP-ribose) polymerase
      (PARP) and SL pairs involved in mitochondrial death signaling pathways published
      in the last 3 years. EXPERT OPINION: Most of the currently used chemotherapeutic
      agents will destroy cells irrespective of whether they are cancer cells or fast
      growing normal cells; but SL is one of the approaches being developed with
      potential as a selective cancer therapy. PARP inhibitors, such as olaparib, are
      useful in BRCA mutated cancer cells and are also used in combination with other
      drug to enhance their efficacy. Research on PARP inhibitors is progressing at a
      good pace but there are still some significant challenges that must be addressed.

PMID- 26211782
TI  - A comparison of different vitrification devices and the effect of blastocoele
      collapse on the cryosurvival of in vitro produced porcine embryos.
AB  - The aim of this study was to determine the optimum conditions for vitrifying in
      vitro produced day 7 porcine embryos using different vitrification devices and
      blastocoele collapse methods. Firstly embryos were collapsed by micro-pipetting,
      needle puncture and sucrose with and without conducting vitrification. In the
      next experiment, non-collapsed embryos were vitrified in an open device using
      either superfine open-pulled straws (SOPS) or the CryoLoop(TM) system, or
      vitrified in a closed device using either the CryoTip(TM) or Cryo Bio(TM)'s high
      security vitrification system (HSV). The post-thaw survival of embryos vitrified
      in the open devices did not differ significantly (SOPS: 37.3%; CryoLoop(TM):
      37.3%) nor did the post-thaw survival of embryos vitrified in the closed devices
      (CryoTipTM: 38.5%; HSV: 42.5%). The re-expansion rate of embryos that were
      collapsed via micro-pipetting (76.0%) did not differ from those that were
      punctured (75.0%) or collapsed via sucrose (79.6%) when vitrification was not
      performed. However, embryos collapsed via sucrose solutions (24.5%) and needle
      puncture (16.0%) prior to vitrification were significantly less likely to survive
      vitrification than the control (non-collapsed) embryos (53.6%, P < 0.05). The
      findings show that both open and closed vitrification devices were equally
      effective for the vitrification of porcine blastocysts. Collapsing blastocysts
      prior to vitrification did not improve survival, which is inconsistent with the
      findings of studies in other species. This may be due to the extremely sensitive
      nature of porcine embryos, and/or the invasiveness of the collapsing procedures.

PMID- 26211784
TI  - The relation between the effect of a subhypnotic dose of thiopental on claw pain
      threshold in rats and adrenalin, noradrenalin and dopamine levels.
AB  - Thiopental sodium (TPS) needs to be applied together with adrenalin in order to
      establish its analgesic effect in general anesthesia. We aimed to investigate the
      effect of TPS on the claw pain threshold in rats and evaluated its relationship
      with endogenous adrenalin (ADR), noradrenalin (NDR), and dopamine (DOP) levels.
      Intact and adrenalectomized rats were used in the experiment. Intact animals were
      divided into the following groups: 15 mg/kg TPS (TS), 0.3 mg/kg ADR+15 mg/kg TPS
      (ATS) and 0.3 mg/kg ADR alone (ADR). Adrenalectomized animals were divided into
      the following groups: 15 mg/kg TPS (A-TS), 0.3 mg/kg ADR+15 mg/kg TPS (A-ATS) and
      0.3 mg/kg ADR alone (A-ADR). Claw pain threshold and blood ADR, NDR, and DOP
      levels were measured. The TS group's claw pain threshold was found low. However,
      the claw pain thresholds of the ATS and ADR groups increased significantly. In
      the A-TS group, the pain threshold decreased compared with normal, and in the A
      ATS and A-ADR groups, the pain threshold increased. TPS reduced the blood ADR
      levels in intact rats; however, no significant changes were observed in the NDR
      and DOP levels. #TPS provides hyperalgesia by reducing the production of ADR in
      rats. The present study shows that to achieve analgesic activity, TPS needs to be
      applied together with ADR. 

PMID- 26211785
TI  - A Death Involving a Fired and Deflected Bullet: A Case Report from Lyon
      University Institute of Forensic Science, France.
AB  - In case of gunshot deaths, atypical wounds can make the distinction between
      entrance and exit wounds harder. They may be due either to anatomical reasons or
      to diverse cogent ballistic arguments. The reported case pertains to a fatal
      hunting accident involving an expanded conical point bullet against the neck with
      both atypical entrance and exit wounds. Ballistic analyses including test firings
      allowed a better understanding of the external and internal findings. Upon
      premature impact with an intermediary target, the bullet experienced expansion in
      the formation of sharp brass petals responsible for a star-shaped entry wound.
      The trajectory of the deformed high energy projectile through the victim's body
      was then deviated by the cervical column, causing it to be tangential to the skin
      when exiting the body. The description of such atypical cases may benefit other
      experts and may assist in their investigation into similar cases. 

PMID- 26211786
TI  - Intrarenal B Cell Cytokines Promote Transplant Fibrosis and Tubular Atrophy.
AB  - Renal transplantation is the optimum treatment for end-stage renal failure. B
      cells have been identified in chronic allograft damage (CAD) and associated with
      the development of tertiary lymphoid tissue within the human renal allograft. We
      performed renal transplantation in mice to model CAD and identified B cells
      forming tertiary lymphoid tissue with germinal centers. Intra-allograft B220(+) B
      cells comprised of IgM(high) CD23(-) B cells, IgM(lo) CD23(+) B cells, and
      IgM(lo) CD23(-) B cells with elevated expression of CD86. Depletion of B cells
      with anti-CD20 was associated with an improvement in CAD but only when
      administered after transplantation and not before. Isolated intra-allograft B
      cells were cultured and shown to synthesize multiple cytokines, the most abundant
      of these were GRO-alpha (CXCL1), RANTES (CCL5), IL-6 and MCP-1 (CCL2). Tubular
      loss was observed with T cell accumulation within the allograft and development
      of interstitial fibrosis, whilst type III collagen deposition was observed in
      areas of F4/80(+) macrophages and PDGFR-beta(+) and transgelin(+) fibroblasts,
      all of which were reduced by B cell depletion. We have shown that intra-allograft
      B cells are key mediators of CAD. B cells possibly contribute to CAD by intra
      allograft secretion of cytokines and chemokines. 

PMID- 26211787
TI  - Ureteral length in live donor kidney transplantation; Does size matter?
AB  - The aim of this study was to evaluate the role of ureteral length on urological
      complications. Data were retrospective collected from the INEX-trial database, a
      RCT to compare the intravesical to the extravesical ureteroneocystostomy.
      Ureteral length was measured in 198 recipients and used to divide recipients into
      three categories based on interquartile ranges: short (<=8.5 cm), medium (8.6
      10.9 cm) and long ureters (>=11 cm). Urological complications were defined as the
      number of percutaneous nephrostomy placements (PCN). Fifty recipients fell into
      the short, 98 into the medium and 50 recipients into the long ureter category.
      Median follow-up was 26 (range 2-45) months. There was no significant difference
      in number of PCN placements between the categories. There were 9 (18%) PCN
      placements in the short ureter category, 21 (20%) in medium ureter category and
      10 (21%) in the long ureter category, P = 0.886. Risk factor analysis for gender,
      arterial multiplicity and type of ureteroneocystostomy showed no differences in
      PCN placements between the three ureteral length categories. We conclude that
      ureteral length alone does not seem to influence the number of urological
      complications. 

PMID- 26211788
TI  - Uncovering Cryptic Diversity in Two Amoebozoan Species Using Complete
      Mitochondrial Genome Sequences.
AB  - The Amoebozoa are a major eukaryotic lineage that encompasses a wide range of
      amoeboid organisms. The group is understudied from a systematic perspective:
      molecular tools have only been applied in the last 15 yr. Hence, there is an
      undersampling of both genes and taxa in the group especially compared to plants,
      animals, and fungi. Here, we present the complete mitochondrial genomes of two
      ubiquitous and abundant morpho-species (Acanthamoeba castellanii and Vermamoeba
      vermiformis). Both have mitochondrial genomes of close relatives previously
      available, enabling insights into recent divergences at a genomic scale, while
      simultaneously offering comparisons with divergence estimates obtained from
      traditionally used single genes, SSU rDNA and cox1. The newly sequenced mt
      genomes are significantly divergent from their previously sequenced conspecifics
      (A. castellannii 16.4% divergence at nucleotide level and 10.4% amino acid; V.
      vermiformis 21.6% and 13.1%, respectively), while divergence at the small subunit
      ribosomal DNA is below 1% within both species. Morphological analyses determined
      that these lineages are indistinguishable from their previously sequenced
      counterparts. Phylogenetic reconstructions using 26 mt genes also indicate a
      level of divergence that is comparable to divergence among species, while
      reconstructions using the small subunit ribosomal DNA (SSU rDNA) do not. In
      addition, we demonstrate that between closely related taxa, there are high levels
      of synteny, which can be explored for primer design to obtain larger fragments
      than the traditional barcoding genes. We conclude that, although most systematic
      work has relied on SSU, this gene alone can severely underestimate diversity.
      Thus, we suggest that the mt genome emerges as an alternative for unraveling the
      lower level phylogenetic relationships of Amoebozoa.

PMID- 26211789
TI  - Assessment of an iPad Loan Program in an Academic Medical Library: A Case Study.
AB  - An academic medical library expanded its iPad loan service to multiple campus
      libraries and conducted an assessment of the service. iPads loaded with medical
      and educational apps were loaned for two-week checkouts from five library campus
      locations. Device circulation statistics were tracked and users were invited to
      complete an online survey about their experience. Data were gathered and analyzed
      for 11 months. The assessment informed the library on how best to adapt the
      service, including what resources to add to the iPads, and the decision to move
      devices to campuses with more frequent usage. 

PMID- 26211790
TI  - Comparing Subscription-Based Anatomy E-Resources for Collections Development.
AB  - This article describes a chart-based approach for health sciences libraries to
      compare anatomy e-resources. The features, functionalities, and user experiences
      of seven leading subscription-based e-resources were assessed using a chart that
      was iteratively developed by the investigators. Acland's Video Atlas of Human
      Anatomy, Thieme Winking Skull, and Visible Body were the preferred products as
      they respectively excel in cadaver-based videos, self-assessment, and 3D
      graphical manipulation. Moreover, each product affords a pleasant user
      experience. The investigative team found that resources specializing in one
      aspect of anatomy teaching are superior to those that contain a wealth of content
      for diverse audiences. 

PMID- 26211791
TI  - Integrating an Informationist Into Graduate Education: Case Study With
      Preliminary Results.
AB  - An informationist taught, consulted, and mentored graduate students enrolled in a
      graduate research project course in Health Informatics. An observational cohort
      study was conducted to determine the effect of an early (first term) and
      continued (subsequent term) exposure of course-integrated instruction, individual
      consultations, information resource mentoring, and educational collaboration
      partnership on the development of information literacy, research skills, and
      integrative competencies in graduate students. Student progress was assessed by
      survey, class performance, and faculty feedback. The course-integrated lectures,
      consultations, mentoring, and educational partnership between the informationist
      and academic advisors increased the students' course performance, information
      literacy, and research skills in graduate students. 

PMID- 26211792
TI  - The Lived Experience and Training Needs of Librarians Serving at the Clinical
      Point-of-Care.
AB  - This study examines the emotional experiences and perceptions of librarians
      embedded into clinical care teams and how those perceptions affect their training
      and preparation needs. Qualitative research methodologies were applied to textual
      data drawn from focus groups (n = 21), interviews (n = 2), and an online survey
      (n = 167), supplemented by quantitative survey data. Phenomenological results
      show librarians experience strongly affective responses to clinical rounding.
      Important factors include personal confidence; relationships with team members,
      patients, and families; and the stressful environment. Analysis of librarians'
      perceived educational needs indicates that training must address specialized
      subjects including medical knowledge, clinical culture, and institutional
      politics.

PMID- 26211794
TI  - ClinicalKey 2.0: Upgrades in a Point-of-Care Search Engine.
AB  - ClinicalKey 2.0, launched September 23, 2014, offers a mobile-friendly design
      with a search history feature for targeting point-of-care resources for health
      care professionals. Browsing is improved with searchable, filterable listings of
      sources highlighting new resources. ClinicalKey 2.0 improvements include more
      than 1,400 new Topic Pages for quick access to point-of-care content. A sample
      search details some of the upgrades and content options. 

PMID- 26211793
TI  - Outreach to Addiction-A Month of Investing in Ability: A Case Study.
AB  - Coordinated and organized by a disabilities librarian, the University of
      Michigan's Council for Disability Concerns provides annual outreach programs with
      biomedical themes through a series of educational events known as Investing in
      Ability. Every effort is made to reach the campus and the surrounding community
      to promote the council's goals of increased accessibility for all individuals
      with physical or developmental challenges, to de-stigmatize such conditions, and
      to educate the audience about disability-related topics. In 2014, Investing in
      Ability focused on the pressing and pervasive topic of addiction. Because
      audience attendance and interest were the highest that they have ever been for
      previous Investing in Ability events, the project will serve as a model in the
      future, possibly as one for other committees to emulate. 

PMID- 26211795
TI  - The "Internet of Things": What It Is and What It Means for Libraries.
AB  - The "Internet of Things" is a popular buzzword but a poorly understood concept.
      In short, it refers to everyday objects that can sense the environment around
      them and communicate that data to other objects and services via the Internet.
      This column will briefly explain what the Internet of Things is and how it might
      be useful for libraries. It will also discuss some of the problems with and
      objections to this technology. A list of currently available Internet of Things
      examples is also included. 

PMID- 26211796
TI  - Developing an Interface to Order and Document Health Education Videos in the
      Electronic Health Record.
AB  - Transitioning to electronic health records (EHRs) provides an opportunity for
      health care systems to integrate educational content available on interactive
      patient systems (IPS) with the medical documentation system. This column
      discusses how one hospital simplified providers' workflow by making it easier to
      order educational videos and ensure that completed education is documented within
      the medical record. Integrating the EHR and IPS streamlined the provision of
      patient education, improved documentation, and supported the organization in
      meeting core requirements for Meaningful Use. 

PMID- 26211797
TI  - Effecting Change in an Evidence-Based Medicine Curriculum: Librarians' Role in a
      Pediatric Residency Program.
AB  - Librarians for the joint Phoenix Children's Hospital/Maricopa Medical Center
      Pediatric Residency Program were asked to assist on the Evidence-Based Medicine
      (EBM) Subcommittee for the program. Faculty was open to recommendations for
      revising and improving the curriculum and desired librarian assistance in
      completing the task. The annual program review and conference evaluations
      revealed a gap between the objectives of the EBM curriculum and the residents'
      perceived abilities to integrate knowledge into meaningful literature searches.
      This column demonstrates how librarians can collaborate with their residency
      programs to revise and improve processes to effect change in their program's EBM
      curriculum. 

PMID- 26211804
TI  - The generation of phosphoserine stretches in phosphoproteins: mechanism and
      significance.
AB  - In the infancy of studies on protein phosphorylation the occurrence of clusters
      of three or more consecutive phosphoseryl residues in secreted and in cellular
      phosphoproteins was reported. Later however, while the reversible phosphorylation
      of Ser, Thr and Tyr residues was recognized to be the most frequent and general
      mechanism of cell regulation and signal transduction, the phenomenon of multi
      phosphorylation of adjacent residues was entirely neglected. Nowadays, in the
      post-genomic era, the availability of large phosphoproteomics database makes
      possible a comprehensive re-visitation of this intriguing aspect of protein
      phosphorylation, aimed at shedding light on both its mechanistic occurrence and
      its functional meaning. Here we describe an analysis of the human phosphoproteome
      disclosing the existence of more than 800 rows of 3 to >10 consecutive
      phosphoamino acids, composed almost exclusively of phosphoserine, while clustered
      phosphothreonines and phosphotyrosines are almost absent. A scrutiny of these
      phosphorylated rows supports the conclusion that they are generated through the
      major contribution of a few hierarchical protein kinases, with special reference
      to CK2. Also well documented is the combined intervention of CK1 and GSK3, the
      former acting as priming and primed, the latter as primed kinase. The by far
      largest proportion of proteins containing (pS)n clusters display a nuclear
      localization where they play a prominent role in the regulation of transcription.
      Consistently the molecular function of the by far largest majority of these
      proteins is the ability to bind other macromolecules and/or nucleotides and metal
      ions. A "String" analysis performed under stringent conditions reveals that >80%
      of them are connected to each other by physical and/or functional links, and that
      this network of interactions mostly take place at the nuclear level. 

PMID- 26211805
TI  - End of the line: Line bisection, an unreliable measure of approach and avoidance
      motivation.
AB  - Approach motivation leads to greater left hemisphere activation, whereas an
      avoidant motivational state activates the right hemisphere. Recent research,
      which served as the basis for the current experiment, suggests line bisection
      provides a simple measure of approach/avoidance lateralisation. Findings from
      Experiment 1 indicated that the landmark task was sensitive enough to identify
      lateral asymmetries evoked by happy and angry faces; however, follow-up
      experiments failed to replicate this finding. When task instructions were
      slightly modified or when a mixed design was used, motivation did not influence
      landmark task performance. The use of images in lieu of faces also failed to
      produce a significant effect. Importantly, a straight replication of Experiment 1
      produced a null result. Line bisection does not appear to be a suitable measure
      of lateralised approach/avoidance biases, possibly due to the high individual
      variability inherent in visuospatial biases. Implications for null hypothesis
      significance testing are also discussed. 

PMID- 26211806
TI  - Correlation of natural tooth colour with aging in the Spanish population.
AB  - OBJECTIVES: To analyse natural tooth colour in the Spanish population according
      to the colour coordinates lightness (L*), chroma (C*), hue (h*), red-green axis
      (a*) and yellow-blue axis (b*) in order to quantify the correlation and changes
      of tooth colour with age and sex. METHODS: Natural tooth colour was measured in a
      sample of 1,361 Spanish participants of both sexes distributed within an age
      range of 16 to 89 years. The Easyshade Compact spectrophotometer was used and the
      CIELAB and CIELCh systems were followed. RESULTS: Pearson's bivariate
      correlations between age and colour coordinates were highly significant for L*
      (r=-0.674, P<=0.001), h* (r=-0.468, P<=0.001) and C* (r=0.417, P<=0.001). The
      correlation between age and colour coordinates was stronger for men than for
      women, for all colour coordinates. The results showed that C*, b* and a*
      increased by 0.60, 0.56 and 0.26 units/year on average, respectively, whereas L*
      and h* decreased progressively with age (by 0.60 units/year, on average), and
      colour differences increased in a systematic way as the gap between the ages
      being compared grew wider. CONCLUSIONS: The strongest correlation was found
      between age and L*, then between age and h* (both inverse relationships) and then
      between age and a*, C* and b* (direct relationships). In addition, a similar
      degree of change in the colour coordinates L*, C* and h* (of 0.60 units/year on
      average) was observed for natural tooth colour. Knowledge of the chromatic range
      of natural teeth may help to choose colour for the replacement of missing
      elements.

PMID- 26211807
TI  - Geographic/ethnic variability of chromosomal and molecular abnormalities in
      leukemia.
AB  - In 1963, Jean Bernard, a French hematologist, opened a new chapter in hematology
      called geographic hematology ('Hematologie Geographique'). He distinguished two
      research avenues. One dealt with the differences between the various populations
      (ethnic hematology), the other with various environmental factors (environmental
      hematology). In recent years, focus has been put on analyzing the genetic
      susceptibility in cancer and hematological malignancies, particularly in
      childhood acute lymphoblastic leukemia, using specific gene or (genome-wide
      association study) approach. However, almost 30 years ago, it was suggested by a
      few workers that chromosomal abnormalities observed in leukemia could have a
      geographic and/or ethnic distribution. In this review, we analyze the literature
      on chromosomal and molecular abnormalities in several types of leukemia. 

PMID- 26211808
TI  - delta Subunit-containing GABAA receptors are preferred targets for the centrally
      acting analgesic flupirtine.
AB  - BACKGROUND AND PURPOSE: The Kv 7 channel activator flupirtine is a clinical
      analgesic characterized as 'selective neuronal potassium channel opener'.
      Flupirtine was found to exert comparable actions at GABAA receptors and Kv 7
      channels in neurons of pain pathways, but not in hippocampus. EXPERIMENTAL
      APPROACH: Expression patterns of GABAA receptors were explored in immunoblots of
      rat dorsal root ganglia, dorsal horns and hippocampi using antibodies for 10
      different subunits. Effects of flupirtine on recombinant and native GABAA
      receptors were investigated in patch clamp experiments and compared with the
      actions on Kv 7 channels. KEY RESULTS: Immunoblots pointed towards alpha2,
      alpha3, beta3 and gamma2 subunits as targets, but in all gamma2-containing
      receptors the effects of flupirtine were alike: leftward shift of GABA
      concentration-response curves and diminished maximal amplitudes. After
      replacement of gamma2S by delta, flupirtine increased maximal amplitudes.
      Currents through alpha1beta2delta receptors were more enhanced than those through
      Kv 7 channels. In hippocampal neurons, flupirtine prolonged inhibitory
      postsynaptic currents, left miniature inhibitory postsynaptic currents (mIPSCs)
      unaltered and increased bicuculline-sensitive tonic currents; penicillin
      abolished mIPSCs, but not tonic currents; concentration-response curves for GABA
      induced currents were shifted to the left by flupirtine without changes in
      maximal amplitudes; in the presence of penicillin, maximal amplitudes were
      increased; GABA-induced currents in the presence of penicillin were more
      sensitive towards flupirtine than K(+) currents. In dorsal horn neurons, currents
      evoked by the delta-preferring agonist THIP (gaboxadol) were more sensitive
      towards flupirtine than K(+) currents. CONCLUSIONS AND IMPLICATIONS: Flupirtine
      prefers delta-containing GABAA receptors over gamma-containing ones and over Kv 7
      channels.

PMID- 26211810
TI  - A case of upper gingiva carcinoma with chronic graft-versus-host disease after
      allogenic bone marrow transplantation.
AB  - Oral squamous cell carcinoma (OSCC) is one of the most common solid tumours
      occurring after haematopoietic stem cell transplantation (HSCT), especially in
      patients with chronic graft-versus-host-disease (cGVHD). We describe a case of
      OSCC that developed in a 51-year-old male 22 years after he had received
      allogeneic HSCT from his human leukocyte antigen-identical sister as a treatment
      for acute myelocytic leukaemia. The patient had presented with multiple white
      patchy lesions on the palatal gingiva and mucosa 16 years after HSCT; these
      lesions were consistent with the clinical features of cGVHD. Six years later,
      oral examination and biopsy revealed upper gingival squamous cell carcinoma (SCC)
      in areas of cGVHD, and he underwent tumour excision. Follow-up examination at 2
      years and 4 months after the operation revealed no evidence of recurrence of
      local SCC or metastasis of the cervical lymph node. The current case highlights
      the susceptibility of patients with cGVHD to the development of OSCC even two
      decades after HSCT. Therefore, we recommend careful long-term follow-up of the
      oral cavity for patients with cGVHD. 

PMID- 26211809
TI  - Cumulative exposure to short sleep and body mass outcomes: a prospective study.
AB  - Short sleep duration is associated with excess body mass among adolescents and
      young adults. The mechanisms theorized to drive that association suggest that
      persistent exposure to short sleep should be associated with greater
      accumulations of body mass. We use prospective cohort data from four waves of the
      National Longitudinal Study of Adolescent to Adult Health (1994-2009; n = 14 800)
      to examine associations between cumulative exposure to short sleep throughout
      adolescence and early adulthood and obesity and elevated waist circumference
      outcomes. We compare several clinical and distribution-based standards of short
      sleep to assess which measures are associated most strongly with body mass.
      Cumulative exposure to short sleep exhibits dose-response associations with
      obesity and elevated waist circumference. Relative to respondents with no
      instances of short sleep, those who slept -0.50 standard deviations or less than
      the age and sex-specific average sleep hours in all four waves had 1.45 [95%
      confidence interval (CI): 1.03, 2.04] times the odds of being obese and 1.45 (95%
      CI: 1.02, 2.06) times the odds of having an elevated waist circumference. Our
      findings suggest that cumulative exposure to short sleep during adolescence and
      young adulthood may play an important role in the etiology of obesity and
      elevated waist circumference during this important developmental period.

PMID- 26211811
TI  - Adaptive multi-level conditional random fields for detection and segmentation of
      small enhanced pathology in medical images.
AB  - Detection and segmentation of large structures in an image or within a region of
      interest have received great attention in the medical image processing domains.
      However, the problem of small pathology detection and segmentation still remains
      an unresolved challenge due to the small size of these pathologies, their low
      contrast and variable position, shape and texture. In many contexts, early
      detection of these pathologies is critical in diagnosis and assessing the outcome
      of treatment. In this paper, we propose a probabilistic Adaptive Multi-level
      Conditional Random Fields (AMCRF) with the incorporation of higher order cliques
      for detecting and segmenting such pathologies. In the first level of our
      graphical model, a voxel-based CRF is used to identify candidate lesions. In the
      second level, in order to further remove falsely detected regions, a new CRF is
      developed that incorporates higher order textural features, which are invariant
      to rotation and local intensity distortions. At this level, higher order textures
      are considered together with the voxel-wise cliques to refine boundaries and is
      therefore adaptive. The proposed algorithm is tested in the context of detecting
      enhancing Multiple Sclerosis (MS) lesions in brain MRI, where the problem is
      further complicated as many of the enhancing voxels are associated with normal
      structures (i.e. blood vessels) or noise in the MRI. The algorithm is trained and
      tested on large multi-center clinical trials from Relapsing-Remitting MS
      patients. The effect of several different parameter learning and inference
      techniques is further investigated. When tested on 120 cases, the proposed method
      reaches a lesion detection rate of 90%, with very few false positive lesion
      counts on average, ranging from 0.17 for very small (3-5 voxels) to 0 for very
      large (50+ voxels) regions. The proposed model is further tested on a very large
      clinical trial containing 2770 scans where a high sensitivity of 91% with an
      average false positive count of 0.5 is achieved. Incorporation of contextual
      information at different scales is also explored. Finally, superior performance
      is shown upon comparing with Support Vector Machine (SVM), Random Forest and
      variant of an MRF. 

PMID- 26211812
TI  - Immediate hypersensitivity reactions to corticosteroids.
AB  - OBJECTIVE: To review the literature on immediate hypersensitivity reactions to
      corticosteroids and classify them according to manifestations, routes of
      exposure, causative preparations, diagnostic tests, and management. DATA SOURCES:
      PubMed search for English-language publications from January 1, 2004 through
      December 31, 2014 using search terms corticosteroid, glucocorticoid, or steroid
      combined with hypersensitivity, allergy, or anaphylaxis. STUDY SELECTION: Only
      reports of immediate hypersensitivity reactions that occurred sooner than 24
      hours after administration of a corticosteroid were included. Excluded were
      reports on patients with delayed reactions, including contact dermatitis.
      RESULTS: Forty-eight articles fulfilled the criteria, reporting 120 reactions in
      106 patients 2 to 90 years of age (55 male and 51 female). The most commonly
      reported manifestation was anaphylaxis in 60.8% (73 of 120) followed by urticaria
      and/or angioedema in 26.7%. Exposure to corticosteroid was through any route,
      with intravenous being the most common (44.2%, 53 of 120), followed by oral in
      25.8% and intra-articular in 11.7%. Methylprednisolone was the most commonly
      implicated (40.8%) followed by prednisolone (20.0%). Some reacted to more than 1
      preparation. Pharmacologically-inactive ingredients were implicated in 28.3%.
      Diagnosis was based primarily on medical history and in most cases was confirmed
      by challenge testing. Skin tests were positive in 74.1%. The vast majority of
      patients tolerated at least 1 alternative preparation, and very rarely
      desensitization was required. CONCLUSION: Corticosteroids seem to be rare causes
      of immediate hypersensitivity reactions but possibly are misdiagnosed or under
      reported relative to their worldwide use. Physicians should be cognizant of this
      entity and identify safe alternative preparations.

PMID- 26211813
TI  - Soy Leaf Extract Containing Kaempferol Glycosides and Pheophorbides Improves
      Glucose Homeostasis by Enhancing Pancreatic beta-Cell Function and Suppressing
      Hepatic Lipid Accumulation in db/db Mice.
AB  - This study investigated the molecular mechanisms underlying the antidiabetic
      effect of an ethanol extract of soy leaves (ESL) in db/db mice. Control groups
      (db/+ and db/db) were fed a normal diet (ND), whereas the db/db-ESL group was fed
      ND with 1% ESL for 8 weeks. Dietary ESL improved glucose tolerance and lowered
      plasma glucose, glycated hemoglobin, HOMA-IR, and triglyceride levels. The
      pancreatic insulin content of the db/db-ESL group was significantly greater than
      that of the db/db group. ESL supplementation altered pancreatic IRS1, IRS2, Pdx1,
      Ngn3, Pax4, Ins1, Ins2, and FoxO1 expression. Furthermore, ESL suppressed lipid
      accumulation and increased glucokinase activity in the liver. ESL primarily
      contained kaempferol glycosides and pheophorbides. Kaempferol, an aglycone of
      kaempferol glycosides, improved beta-cell proliferation through IRS2-related
      FoxO1 signaling, whereas pheophorbide a, a product of chlorophyll breakdown,
      improved insulin secretion and beta-cell proliferation through IRS1-related
      signaling with protein kinase A in MIN6 cells. ESL effectively regulates glucose
      homeostasis by enhancing IRS-mediated beta-cell insulin signaling and suppressing
      SREBP-1-mediated hepatic lipid accumulation in db/db mice. 

PMID- 26211814
TI  - Clinical, genealogical and molecular investigation of the xeroderma pigmentosum
      type C complementation group in Tunisia.

PMID- 26211815
TI  - Pharmacy quality alliance measure: adherence to non-warfarin oral anticoagulant
      medications.
AB  - BACKGROUND: The Pharmacy Quality Alliance (PQA) recently endorsed adherence to
      non-warfarin anticoagulant agents as a new performance measure, but the Medicare
      Part D Star Ratings program has not yet adopted the measure. The current study
      aims to assess the real-world adherence to medication of patients who used non
      vitamin-K-antagonist oral anticoagulants (NOACs) based on the PQA's adherence
      measure. METHODS: Healthcare claims from the Humana database during the year of
      2013 were analyzed. Patients older than 18 with >=2 dispensings of NOAC agents,
      at least 180 days apart between two NOAC dispensings in 2013 (a criterion to
      include chronic users), with >=60 days of supply, and >=180 days of continuous
      enrollment prior to the index NOAC were identified. The PQA measure on the index
      therapy was calculated as the percentage of patients who had a proportion of days
      covered (PDC) >=0.8 during their follow-up. RESULTS: A total of 9948 NOAC users
      (rivaroxaban: n = 4194, dabigatran: n = 5489, apixaban: n = 265) were identified.
      For rivaroxaban users, the proportion of patients with a PDC >=0.8 (PQA measure)
      at 75.4% was significantly higher compared to dabigatran users (67.6%; P < 0.001)
      and higher compared to apixaban users (70.6%; P = 0.076). When allowing switches
      to other NOAC agents in the PQA measure, rivaroxaban users had a significantly
      higher PQA measure at 76.9% compared to both dabigatran (72.9%; P < 0.001) and
      apixaban (71.3%; P = 0.037) users. Multivariate logistic regression analyses
      corroborated the findings that rivaroxaban had a significantly higher adherence
      compared to the other NOAC agents. LIMITATIONS: Claims data may have contained
      inaccuracies, possible change in patterns over time, and the impossibility of
      knowing whether all supplied tablets were taken. CONCLUSION: Based on the PQA's
      adherence measure, rivaroxaban users were found to have a higher adherence
      compared to dabigatran and apixaban users. Healthcare providers may want to
      consider the impact of anticoagulation selection on their ability to achieve
      quality metrics.

PMID- 26211816
TI  - Medication persistence and discontinuation of rivaroxaban and dabigatran
      etexilate among patients with non-valvular atrial fibrillation.
AB  - OBJECTIVE: To compare real-world persistence and discontinuation among non
      valvular atrial fibrillation (NVAF) patients on rivaroxaban and dabigatran in the
      US. METHODS: A large nationally representative US claims database was used to
      conduct a retrospective cohort analysis of patients with NVAF on rivaroxaban or
      dabigatran between October 2010 and March 2013. The index date was the date of
      the first prescription of rivaroxaban or dabigatran. All patients had >=6 months
      of data prior to the index date and were followed until the earliest of inpatient
      death, end of continuous enrollment, or end of the study period. Rivaroxaban
      patients were matched 1:1 with dabigatran patients using the propensity score
      matching technique. Cox proportional hazards models were employed to estimate the
      adjusted hazard ratios (aHRs) of non-persistence and discontinuation. Persistence
      was defined as absence of a refill gap of >=60 days. Discontinuation was defined
      as no additional refill for at least 90 days and until the end of follow-up.
      RESULTS: A total of 30,337 NVAF patients on rivaroxaban or dabigatran met the
      study criteria. All 7259 rivaroxaban patients were matched 1:1 to dabigatran
      patients. Compared with dabigatran users, rivaroxaban patients were 11% less
      likely to become non-persistent with therapy (aHR: 0.89, 95% CI 0.84-0.95) and
      29% less likely to discontinue therapy (aHR: 0.71, 95% CI 0.66-0.77).
      LIMITATIONS: Claims data are subject to miscoding and inaccuracies. Refill data
      may not fully reflect actual medication taken. Confounding may remain even after
      propensity score matching and additional adjustments in model. Longer follow-up
      may produce more precise estimates of persistence and discontinuation.
      CONCLUSIONS: This matched cohort analysis indicated that, compared to dabigatran,
      rivaroxaban was associated with better persistence and lower rates of
      discontinuation.

PMID- 26211817
TI  - Tamsulosin combined with solifenacin versus tamsulosin monotherapy for male lower
      urinary tract symptoms: a meta-analysis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of tamsulosin and solifenacin
      combination therapy compared with tamsulosin monotherapy for male lower urinary
      tract symptoms (LUTS). METHODS: We identified all eligible studies that compared
      tamsulosin and solifenacin combination therapy with tamsulosin monotherapy for
      male LUTS (up to January 2015). The fixed- or random-effects model was selected
      depending on the proportion of heterogeneity. RESULTS: Seven articles were
      identified as eligible for this meta-analysis, with a total of 3063 participants.
      Synthetic data showed combination therapy had significant improvements in Storage
      International Prostate Symptom Score (WMD = -0.60; 95% CI: -0.81 to -0.38, P <
      0.0001), quality of life (WMD = -0.23; 95% CI: -0.34 to -0.11, P < 0.0001),
      micturitions per 24 hours (WMD = -0.70; 95% CI: -0.86 to -0.55, P < 0.0001) and
      urgency episodes per 24 hours (WMD = -0.26; 95% CI: -0.48 to -0.05, P = 0.018).
      The incidence of adverse effects in the tamsulosin and solifenacin combined
      therapy group (30.82%) was similar to the tamsulosin monotherapy group (25.75%).
      Acute urinary retention was seldom reported in the studies and no clinically
      significant changes regarding Qmax were showed in our meta-analysis. CONCLUSIONS:
      Tamsulosin and solifenacin combination therapy may be a reasonable option for
      male LUTS patients, especially for those who have significant storage symptoms.
      However, PVR should be measured during treatment to assess the increase in PVR or
      the incidence of AUR.

PMID- 26211818
TI  - Autoimmune disorders in patients with T-cell lymphoma: a comprehensive review.
AB  - BACKGROUND: Increased risk of B-cell lymphoma in patients with autoimmune
      diseases is well known. Medical literature also links various autoimmune
      conditions with T-cell lymphomas (TCLs), a rarer but very heterogeneous group of
      generally aggressive neoplasms. METHODS: Herein, we provide a comprehensive
      analysis of the available peer-reviewed literature on epidemiology, clinico
      laboratory features and management of autoimmune diseases in patients with TCL.
      Most relevant publications were identified through searching the PubMed/Medline
      database for articles published from inception to June 2014. FINDINGS: Prevalence
      of various hematologic and non-hematologic autoimmune conditions in patients with
      TCL appears to be increased. Due to the rarity of TCL, scientific literature on
      autoimmune conditions in these patients consists mainly of case series and
      isolated reports. CONCLUSIONS: Autoimmune disorders can develop prior to, during
      or after the onset of TCL. The diagnosis of TCL should prompt early recognition
      of certain autoimmune disorders if clinical suspicion exists. A dysfunctional
      immune response in these patients may be responsible for the occurrence of
      autoimmunity. Conversely, autoimmune conditions might create a favorable milieu
      for T-cell lymphoma pathogenesis. Therefore, their presence should increase the
      suspicion of TCL in an appropriate clinico-laboratory context. There is need for
      larger studies to assess further the TCL-autoimmunity relationship as prognosis
      and management of these patients can be considerably affected.

PMID- 26211819
TI  - Sepsis and beta-blockade: a look into diastolic function.
AB  - There is growing interest on the modulation of the overwhelming sympathetic
      response of septic patients. Beta-blockers appear promising in this respect and,
      although we are at early stage, one large trial and a smaller one have
      demonstrated major beneficial effects. The modulation of diastolic function and
      the optimization of myocardial efficiency by beta-blockade is among the possible
      reason for the improvement in patients with severe sepsis or septic shock. It
      should be also considered that septic patients are at higher risk of cardiac
      arrhythmias and beta-blocker may have a protective effect in this regard. We are
      still at a preliminary stage and more research is needed it seems reasonable that
      beta-blockade will become an option for the treatment of septic patients over the
      next few years. 

PMID- 26211820
TI  - (1)H NMR Spectroscopy of Fecal Extracts Enables Detection of Advanced Colorectal
      Neoplasia.
AB  - Colorectal cancer (CRC) is a growing cause of mortality in developing countries,
      warranting investigation into its etiopathogenesis and earlier diagnosis. Here,
      we investigated the fecal metabolic phenotype of patients with advanced
      colorectal neoplasia and controls using (1)H-nuclear magnetic resonance (NMR)
      spectroscopy and multivariate modeling. The fecal microbiota composition was
      assessed by quantitative real-time PCR as well as Wif-1 methylation levels in
      stools, serum, and urine and correlated to the metabolic profile of each patient.
      The predictivity of the model was 0.507 (Q(2)Y), and the explained variance was
      0.755 (R(2)Y). Patients with advanced colorectal neoplasia demonstrated increased
      fecal concentrations of four short-chain fatty acids (valerate, acetate,
      propionate, and butyrate) and decreased signals relating to beta-glucose,
      glutamine, and glutamate. The predictive accuracy of the multivariate (1)H NMR
      model was higher than that of the guaiac-fecal occult blood test and the Wif-1
      methylation test for predicting advanced colorectal neoplasia. Correlation
      analysis between fecal metabolites and bacterial profiles revealed strong
      associations between Faecalibacterium prausnitzii and Clostridium leptum species
      with short-chain fatty acids concentration and inverse correlation between
      Faecalibacterium prausnitzii and glucose. These preliminary results suggest that
      fecal metabonomics may potentially have a future role in a noninvasive colorectal
      screening program and may contribute to our understanding of the role of these
      dysregulated molecules in the cross-talk between the host and its bacterial
      microbiota. 

PMID- 26211821
TI  - Improving the utility of colonoscopy: Recent advances in practice.
AB  - Colonoscopy is a frequently performed diagnostic and therapeutic test and the
      primary screening tool in several nationalized bowel cancer screening programs.
      There has been a considerable focus on maximizing the utility of colonoscopy.
      This has occurred in four key areas: Optimizing patient selection to reduce
      unnecessary or low yield colonoscopy has offered cost-benefit improvements in
      population screening. Improving quality assurance, through the development of
      widely accepted quality metrics for use in individual practice and the research
      setting, has offered measurable improvements in colonoscopic yield. Significant
      improvements have been demonstrated in colonoscopic technique, from the
      administration of preparation to the techniques employed during withdrawal of the
      colonoscope. Improved techniques to avoid post-procedural complications have also
      been developed-further maximizing the utility of colonoscopy. The aim of this
      review is to summarize the recent evidence-based advances in colonoscopic
      practice that contribute to the optimal practice of colonoscopy. 

PMID- 26211822
TI  - Ovarian hilar proliferations resembling Sertoli cell tumours: microscopic
      neoplasms or non-neoplastic remnants?
AB  - AIMS: To describe four cases of incidentally detected microscopic ovarian hilar
      Sertoli cell proliferation, a phenomenon that, as far as we are aware, has not
      been previously reported, and to discuss the differential diagnosis of these
      lesions. METHODS AND RESULTS: The proliferations occurred in women aged 35-62
      years, and were composed of solid and hollow tubules that were morphologically
      and immunohistochemically in keeping with Sertoli cells. Two cases were
      bilateral. CONCLUSIONS: We feel that these uncommon proliferations are likely to
      represent non-neoplastic embryological remnants rather than hilar Sertoli cell
      tumours.

PMID- 26211823
TI  - Postmenopausal breast cancer: a best endocrine strategy?

PMID- 26211824
TI  - Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of
      individual patient data from randomised trials.
AB  - BACKGROUND: Bisphosphonates have profound effects on bone physiology, and could
      modify the process of metastasis. We undertook collaborative meta-analyses to
      clarify the risks and benefits of adjuvant bisphosphonate treatment in breast
      cancer. METHODS: We sought individual patient data from all unconfounded trials
      in early breast cancer that randomised between bisphosphonate and control.
      Primary outcomes were recurrence, distant recurrence, and breast cancer
      mortality. Primary subgroup investigations were site of first distant recurrence
      (bone or other), menopausal status (postmenopausal [combining natural and
      artificial] or not), and bisphosphonate class (aminobisphosphonate [eg,
      zoledronic acid, ibandronate, pamidronate] or other [ie, clodronate]). Intention
      to-treat log-rank methods yielded bisphosphonate versus control first-event rate
      ratios (RRs). FINDINGS: We received data on 18,766 women (18,206 [97%] in trials
      of 2-5 years of bisphosphonate) with median follow-up 5.6 woman-years, 3453 first
      recurrences, and 2106 subsequent deaths. Overall, the reductions in recurrence
      (RR 0.94, 95% CI 0.87-1.01; 2p=0.08), distant recurrence (0.92, 0.85-0.99;
      2p=0.03), and breast cancer mortality (0.91, 0.83-0.99; 2p=0.04) were of only
      borderline significance, but the reduction in bone recurrence was more definite
      (0.83, 0.73-0.94; 2p=0.004). Among premenopausal women, treatment had no apparent
      effect on any outcome, but among 11 767 postmenopausal women it produced highly
      significant reductions in recurrence (RR 0.86, 95% CI 0.78-0.94; 2p=0.002),
      distant recurrence (0.82, 0.74-0.92; 2p=0.0003), bone recurrence (0.72, 0.60
      0.86; 2p=0.0002), and breast cancer mortality (0.82, 0.73-0.93; 2p=0.002). Even
      for bone recurrence, however, the heterogeneity of benefit was barely significant
      by menopausal status (2p=0.06 for trend with menopausal status) or age (2p=0.03),
      and it was non-significant by bisphosphonate class, treatment schedule, oestrogen
      receptor status, nodes, tumour grade, or concomitant chemotherapy. No differences
      were seen in non-breast cancer mortality. Bone fractures were reduced (RR 0.85,
      95% CI 0.75-0.97; 2p=0.02). INTERPRETATION: Adjuvant bisphosphonates reduce the
      rate of breast cancer recurrence in the bone and improve breast cancer survival,
      but there is definite benefit only in women who were postmenopausal when
      treatment began. FUNDING: Cancer Research UK, Medical Research Council.

PMID- 26211825
TI  - Bisphosphonates, bone, and breast cancer recurrence.

PMID- 26211826
TI  - A medical-toxicological view of tattooing.
AB  - Long perceived as a form of exotic self-expression in some social fringe groups,
      tattoos have left their maverick image behind and become mainstream, particularly
      for young people. Historically, tattoo-related health and safety regulations have
      focused on rules of hygiene and prevention of infections. Meanwhile, the
      increasing popularity of tattooing has led to the development of many new
      colours, allowing tattoos to be more spectacular than ever before. However,
      little is known about the toxicological risks of the ingredients used. For risk
      assessment, safe intradermal application of these pigments needs data for
      toxicity and biokinetics and increased knowledge about the removal of tattoos.
      Other concerns are the potential for phototoxicity, substance migration, and the
      possible metabolic conversion of tattoo ink ingredients into toxic substances.
      Similar considerations apply to cleavage products that are formed during laser
      assisted tattoo removal. In this Review, we summarise the issues of concern,
      putting them into context, and provide perspectives for the assessment of the
      acute and chronic health effects associated with tattooing. 

PMID- 26211827
TI  - Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta
      analysis of the randomised trials.
AB  - BACKGROUND: The optimal ways of using aromatase inhibitors or tamoxifen as
      endocrine treatment for early breast cancer remains uncertain. METHODS: We
      undertook meta-analyses of individual data on 31,920 postmenopausal women with
      oestrogen-receptor-positive early breast cancer in the randomised trials of 5
      years of aromatase inhibitor versus 5 years of tamoxifen; of 5 years of aromatase
      inhibitor versus 2-3 years of tamoxifen then aromatase inhibitor to year 5; and
      of 2-3 years of tamoxifen then aromatase inhibitor to year 5 versus 5 years of
      tamoxifen. Primary outcomes were any recurrence of breast cancer, breast cancer
      mortality, death without recurrence, and all-cause mortality. Intention-to-treat
      log-rank analyses, stratified by age, nodal status, and trial, yielded aromatase
      inhibitor versus tamoxifen first-event rate ratios (RRs). FINDINGS: In the
      comparison of 5 years of aromatase inhibitor versus 5 years of tamoxifen,
      recurrence RRs favoured aromatase inhibitors significantly during years 0-1 (RR
      0.64, 95% CI 0.52-0.78) and 2-4 (RR 0.80, 0.68-0.93), and non-significantly
      thereafter. 10-year breast cancer mortality was lower with aromatase inhibitors
      than tamoxifen (12.1% vs 14.2%; RR 0.85, 0.75-0.96; 2p=0.009). In the comparison
      of 5 years of aromatase inhibitor versus 2-3 years of tamoxifen then aromatase
      inhibitor to year 5, recurrence RRs favoured aromatase inhibitors significantly
      during years 0-1 (RR 0.74, 0.62-0.89) but not while both groups received
      aromatase inhibitors during years 2-4, or thereafter; overall in these trials,
      there were fewer recurrences with 5 years of aromatase inhibitors than with
      tamoxifen then aromatase inhibitors (RR 0.90, 0.81-0.99; 2p=0.045), though the
      breast cancer mortality reduction was not significant (RR 0.89, 0.78-1.03;
      2p=0.11). In the comparison of 2-3 years of tamoxifen then aromatase inhibitor to
      year 5 versus 5 years of tamoxifen, recurrence RRs favoured aromatase inhibitors
      significantly during years 2-4 (RR 0.56, 0.46-0.67) but not subsequently, and 10
      year breast cancer mortality was lower with switching to aromatase inhibitors
      than with remaining on tamoxifen (8.7% vs 10.1%; 2p=0.015). Aggregating all three
      types of comparison, recurrence RRs favoured aromatase inhibitors during periods
      when treatments differed (RR 0.70, 0.64-0.77), but not significantly thereafter
      (RR 0.93, 0.86-1.01; 2p=0.08). Breast cancer mortality was reduced both while
      treatments differed (RR 0.79, 0.67-0.92), and subsequently (RR 0.89, 0.81-0.99),
      and for all periods combined (RR 0.86, 0.80-0.94; 2p=0.0005). All-cause mortality
      was also reduced (RR 0.88, 0.82-0.94; 2p=0.0003). RRs differed little by age,
      body-mass index, stage, grade, progesterone receptor status, or HER2 status.
      There were fewer endometrial cancers with aromatase inhibitors than tamoxifen (10
      year incidence 0.4% vs 1.2%; RR 0.33, 0.21-0.51) but more bone fractures (5-year
      risk 8.2% vs 5.5%; RR 1.42, 1.28-1.57); non-breast-cancer mortality was similar.
      INTERPRETATION: Aromatase inhibitors reduce recurrence rates by about 30%
      (proportionately) compared with tamoxifen while treatments differ, but not
      thereafter. 5 years of an aromatase inhibitor reduces 10-year breast cancer
      mortality rates by about 15% compared with 5 years of tamoxifen, hence by about
      40% (proportionately) compared with no endocrine treatment. FUNDING: Cancer
      Research UK, Medical Research Council.

PMID- 26211829
TI  - ADVICE on adenosine to improve atrial fibrillation ablation.

PMID- 26211830
TI  - Plaque-type glomuvenous malformations in a child.

PMID- 26211828
TI  - Adenosine-guided pulmonary vein isolation for the treatment of paroxysmal atrial
      fibrillation: an international, multicentre, randomised superiority trial.
AB  - BACKGROUND: Catheter ablation is increasingly used to manage atrial fibrillation,
      but arrhythmia recurrences are common. Adenosine might identify pulmonary veins
      at risk of reconnection by unmasking dormant conduction, and thereby guide
      additional ablation to improve arrhythmia-free survival. We assessed whether
      adenosine-guided pulmonary vein isolation could prevent arrhythmia recurrence in
      patients undergoing radiofrequency catheter ablation for paroxysmal atrial
      fibrillation. METHODS: We did this randomised trial at 18 hospitals in Australia,
      Europe, and North America. We enrolled patients aged older than 18 years who had
      had at least three symptomatic atrial fibrillation episodes in the past 6 months,
      and for whom treatment with an antiarrhythmic drug failed. After pulmonary vein
      isolation, intravenous adenosine was administered. If dormant conduction was
      present, patients were randomly assigned (1:1) to additional adenosine-guided
      ablation to abolish dormant conduction or to no further ablation. If no dormant
      conduction was revealed, randomly selected patients were included in a registry.
      Patients were masked to treatment allocation and outcomes were assessed by a
      masked adjudicating committee. Patients were followed up for 1 year. The primary
      outcome was time to symptomatic atrial tachyarrhythmia after a single procedure
      in the intention-to-treat population. The trial is registered with
      ClinicalTrials.gov, number NCT01058980. FINDINGS: Adenosine unmasked dormant
      pulmonary vein conduction in 284 (53%) of 534 patients. 102 (69.4%) of 147
      patients with additional adenosine-guided ablation were free from symptomatic
      atrial tachyarrhythmia compared with 58 (42.3%) of 137 patients with no further
      ablation, corresponding to an absolute risk reduction of 27.1% (95% CI 15.9-38.2;
      p<0.0001) and a hazard ratio of 0.44 (95% CI 0.31-0.64; p<0.0001). Of 115
      patients without dormant pulmonary vein conduction, 64 (55.7%) remained free from
      symptomatic atrial tachyarrhythmia (p=0.0191 vs dormant conduction with no
      further ablation). Occurrences of serious adverse events were similar in each
      group. One death (massive stroke) was deemed probably related to ablation in a
      patient included in the registry. INTERPRETATION: Adenosine testing to identify
      and target dormant pulmonary vein conduction during catheter ablation of atrial
      fibrillation is a safe and highly effective strategy to improve arrhythmia-free
      survival in patients with paroxysmal atrial fibrillation. This approach should be
      considered for incorporation into routine clinical practice. FUNDING: Canadian
      Institutes of Health Research, St Jude Medical, Biosense-Webster, and M
      Lachapelle (Montreal Heart Institute Foundation).

PMID- 26211831
TI  - Novel players in the AP2-miR172 regulatory network for common bean nodulation.
AB  - The intricate regulatory network for floral organogenesis in plants that includes
      AP2/ERF, SPL and AGL transcription factors, miR172 and miR156 along with other
      components is well documented, though its complexity and size keep increasing.
      The miR172/AP2 node was recently proposed as essential regulator in the legume
      rhizobia nitrogen-fixing symbiosis. Research from our group contributed to
      demonstrate the control of common bean (Phaseolus vulgaris) nodulation by
      miR172c/AP2-1, however no other components of such regulatory network have been
      reported. Here we propose AGLs as new protagonists in the regulation of common
      bean nodulation and discuss the relevance of future deeper analysis of the
      complex AP2 regulatory network for nodule organogenesis in legumes.

PMID- 26211832
TI  - Computer analysis of foetal monitoring signals.
AB  - Five systems for computer analysis of foetal monitoring signals are currently
      available, incorporating the evaluation of cardiotocographic (CTG) or combined
      CTG with electrocardiographic ST data. All systems have been integrated with
      central monitoring stations, allowing the simultaneous monitoring of several
      tracings on the same computer screen in multiple hospital locations. Computer
      analysis elicits real-time visual and sound alerts for health care professionals
      when abnormal patterns are detected, with the aim of prompting a re-evaluation
      and subsequent clinical action, if considered necessary. Comparison between the
      CTG analyses provided by the computer and clinical experts has been carried out
      in all systems, and in three of them, the accuracy of computer alerts in
      predicting newborn outcomes was evaluated. Comparisons between these studies are
      hampered by the differences in selection criteria and outcomes. Two of these
      systems have just completed multicentre randomised clinical trials comparing them
      with conventional CTG monitoring, and their results are awaited shortly. For the
      time being, there is limited evidence regarding the impact of computer analysis
      of foetal monitoring signals on perinatal indicators and on health care
      professionals' behaviour. 

PMID- 26211833
TI  - Pathophysiology of foetal oxygenation and cell damage during labour.
AB  - A foetus exposed to oxygenation compromise is capable of several adaptive
      responses, which can be categorised into those affecting metabolism and those
      affecting oxygen transport. However, both the extent and duration of the
      impairment in oxygenation will have a bearing on these adaptive responses.
      Although intrapartum events may account for no more than one-third of cases with
      an adverse neurological outcome, they are important because they can be
      influenced successfully. This review describes the mechanisms underlying foetal
      hypoxia during labour, acid-base balance and gas exchange, and the current
      scientific understanding of the role of intrauterine asphyxia in the
      pathophysiology of neonatal encephalopathy and cerebral palsy. Although the
      mechanisms involved include similar initiating events, principally ischaemia and
      excitotoxicity, and similar final common pathways to cell death, there are
      certain unique maturational factors that influence the type and pattern of
      cellular injury. 

PMID- 26211834
TI  - Tim-3 and Tim-4 as the potential targets for antitumor therapy.
AB  - Both Tim-3 and Tim-4 belong to the T-cell immunoglobulin and mucin domain (Tim)
      gene family, which plays a critical role in immunoregulation. Tim-3 has been
      suggested as a negative regulator of anti-tumor immunity due to its function on
      inducing T cells exhaustion in cancer. In addition to its expression on exhausted
      T cells, Tim-3 also has been reported to up-regulate on nature killer (NK) cells
      and promote NK cells functionally exhausted in cancer. While Tim-3 selectively
      expression on most types of leukemia stem cells, it promotes the progression of
      acute myeloid leukemia. Recently, data from experimental models of tumor
      discovered that Tim-3 and Tim-4 up-regulation on tumor associated dendritic cells
      and macrophages attenuated the anti-tumor effects of cancer vaccines and
      chemotherapy. Moreover, co-blockage of Tim-3 and PD-1, Tim-3 and CD137, Tim-3 and
      carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) could enhance cell
      mediated immunity in advanced tumor, and combined treatment with anti-Tim-3 and
      anti-Tim-4 mAbs further increase the efficacy of cancer vaccines. The therapeutic
      manipulation of TIM-3 and TIM-4 may provide a novel strategy to improve the
      clinical efficacy of cancer immunotherapy. 

PMID- 26211835
TI  - HIV-1 Exploits the Host Factor RuvB-like 2 to Balance Viral Protein Expression.
AB  - The correct ratio of the HIV-1 structural protein Gag to the envelope protein
      (Env) is important for maximal virion infectivity. How the virus ensures the
      production of Gag and Env proteins in an appropriate ratio remains unknown. We
      report that HIV-1 exploits the host factor RuvB-like 2 (RVB2) to balance relative
      expression of Gag and Env for efficient production of infectious virions. RVB2
      inhibits Gag expression by interacting with both the encoded Matrix (MA) domain
      of Gag protein and 5' UTR of the translating mRNA and promoting mRNA degradation
      in a translation-dependent manner. This inhibitory activity of RVB2 is
      antagonized by Env through competitive interaction with MA, allowing Gag
      synthesis to proceed when Env levels are adequate for virion assembly. In HIV-1
      positive patients, RVB2 levels positively correlate with viral loads and disease
      progression status. These findings reveal a mechanism by which HIV-1 regulates
      its protein expression. 

PMID- 26211837
TI  - Electrokinetic biomolecule preconcentration using xurography-based micro-nano
      micro fluidic devices.
AB  - In this paper we introduce a low cost rapid prototyping framework for designing
      Micro-Nano-Micro (MNM) fluidic preconcentration device based on ion concentration
      polarization (ICP) phenomenon. Xurography-based microchannels are separated by a
      strip of ion perm-selective Nafion membrane which plays the role of nanofluidic
      potential barrier for the negatively charged molecules. As a result, by using
      this rapid and inexpensive fabrication technique, it is possible to get
      preconcentration plugs as high as 5000 fold with an original symmetric
      electroosmotic flow (EOF) condition. Due to its simplicity and performance, this
      device could be implemented in various bioanalysis systems. 

PMID- 26211836
TI  - Viral Nucleases Induce an mRNA Degradation-Transcription Feedback Loop in
      Mammalian Cells.
AB  - Gamma-herpesviruses encode a cytoplasmic mRNA-targeting endonuclease, SOX, that
      cleaves most cellular mRNAs. Cleaved fragments are subsequently degraded by the
      cellular 5'-3' mRNA exonuclease Xrn1, thereby suppressing cellular gene
      expression and facilitating viral evasion of host defenses. We reveal that
      mammalian cells respond to this widespread cytoplasmic mRNA decay by altering RNA
      Polymerase II (RNAPII) transcription in the nucleus. Measuring RNAPII recruitment
      to promoters and nascent mRNA synthesis revealed that the majority of affected
      genes are transcriptionally repressed in SOX-expressing cells. The
      transcriptional feedback does not occur in response to the initial viral
      endonuclease-induced cleavage, but instead to degradation of the cleaved
      fragments by cellular exonucleases. In particular, Xrn1 catalytic activity is
      required for transcriptional repression. Notably, viral mRNA transcription
      escapes decay-induced repression, and this escape requires Xrn1. Collectively,
      these results indicate that mRNA decay rates impact transcription and that gamma
      herpesviruses use this feedback mechanism to facilitate viral gene expression. 

PMID- 26211838
TI  - Antimicrobial usage in 60 Swedish farrow-to-finish pig herds.
AB  - The aim of this study was to quantify antimicrobial consumption in Swedish farrow
      to-finish pig herds. Sixty herds with 100 sows or more producing more than 500
      fatteners per year participated in a study where data on antimicrobial
      consumption over a period of one year were collected. Data on antimicrobial use
      were collected by substance, administration route and per age category.
      Antimicrobial use was measured as defined daily doses and expressed as treatment
      incidence (TI) per 1000 pig-days at risk. The TIs for growing pigs varied between
      herds, from 1.6 to 116.0 with a median of 14.3. The highest TI was recorded for
      suckling piglets with a median of 54.7 (range; 1.6-367.9), while the median TIs
      for weaners, fatteners and adults were 6.2, 2.8 and 8.4, respectively (range; 0.0
      260.5; 0.0-64.9; 0.0-45.0, respectively). The within herd TIs for the different
      age categories were not correlated. Individual treatment, mainly consisting of
      injectables, was the most common form of application except for weaners for which
      a majority (54.8%) of the treatments were group treatments. Benzylpenicillin was
      the most commonly applied substance except for weaners for which oral
      formulations of tylosin were most common. For fatteners, group treatments
      constituted 8.4% of the total TI. Group treatments with oral colistin were
      applied to suckling piglets in five herds. Group treatments were not applied to
      adult pigs. The TI for weaners was significantly lower for specific pathogen-free
      herds. The results show that the overall antimicrobial use in Swedish farrow-to
      finish pig herds varied to a great extent, and the between-herd variation
      indicates that there is room for improvement of pig health. Targeting suckling
      piglets may be most beneficial, but further studies are required to identify
      specific focus areas which may reduce the need for antimicrobials in this
      particular age group. 

PMID- 26211839
TI  - Salmonella occurrence and Enterobacteriaceae counts in pig feed ingredients and
      compound feed from feed mills in Ireland.
AB  - The purpose of this study was to assess the occurrence of non-typhoidal
      Salmonellae and Enterobacteriaceae counts in raw ingredients and compound feeds
      sampled from feed mills manufacturing pig diets. Between November 2012 and
      September 2013, feed ingredients (n=340) and compound pig feed (n=313) samples
      were collected from five commercial feed mills and one home compounder at various
      locations throughout Ireland. Feed ingredients included cereals, vegetable
      protein sources and by-products of oil extraction and ethanol production. The
      compound feeds included meal and pelleted feed for all stages of pig production.
      Samples were analysed for Salmonella using standard enrichment procedures.
      Recovered isolates were serotyped, characterised for antibiotic resistance and
      subtyped by multi locus variance analysis (MLVA). Total Enterobacteriaceae counts
      were also performed. Salmonella was recovered from 2/338 (0.6%) ingredients
      (wheat and soybean meal), at two of the six mills. Salmonella was also detected
      in 3/317 (0.95%) compound feeds including pelleted feed which undergoes heat
      treatment. All isolates recovered from feed ingredient and compound feed samples
      were verified as Salmonella enterica subsp. enterica serotype (4,[5],12:i:-) that
      lack the expression of flagellar Phase 2 antigens representing monophasic
      variants of Salmonella Typhimurium (4,[5],12:i:-). Isolates exhibited resistance
      to between two and seven antimicrobials. Two distinct MLVA profiles were
      observed, with the same profile recovered from both feed and ingredients,
      although these did not originate at the same mill. There was no relationship
      between the occurrence of Salmonella and a high Enterobacteriaceae counts but it
      was shown that Enterobacteriaceae counts were significantly lower in pelleted
      feed (heat treated) than in meal (no heat treatment) and that Enterobacteriaceae
      counts would be very useful indicator in HACPP programme. Overall, although the
      prevalence of Salmonella in pig feed and feed ingredients in the present study
      was low, even minor Salmonella contamination in feed has the potential to affect
      many herds and may subsequently cause human infection. Furthermore, the recovery
      of a recently emerged serovar with multi-antibiotic resistance is a potential
      cause for concern. 

PMID- 26211840
TI  - [Outbreak of Salmonella Typhimurium infections associated with consumption of
      chorizo in Bizkaia].
AB  - A report is presented on an outbreak of Salmonella enterica serovar Typhimurium
      infection that affected six people. The epidemiological and laboratory
      investigation associated the outbreak with the consumption of homemade chorizo
      purchased at a local street market. The vendor and producer were informed that
      the sale of meat products without sanitary authorization is prohibited, and the
      product was withdrawn from sale.

PMID- 26211841
TI  - Severe thrombocytopenia caused by linezolid poisoning in an underweight
      critically ill patient with renal impairment treated with the recommended doses.

PMID- 26211842
TI  - [Chronic hand infection].

PMID- 26211843
TI  - Nurse practitioner and physician assistant staffing in the patient-centered
      medical homes in New York State.
AB  - BACKGROUND: A cornerstone of patient-centered medical homes (PCMHs) is team-based
      care; however, there is little information about the composition of staff who
      deliver direct primary care in PCMHs. PURPOSE: The purpose of this study was to
      examine the number and distribution of primary care physicians (PCPs), nurse
      practitioners (NPs), and physician assistants (PAs) in PCMH and non-PCMH
      practices located in New York State (N = 7,431). METHOD: Practice based ratios of
      primary care NPs and PAs to PCP were calculated and compared by PCMH
      designations. Designated PCMHs had more NPs and PAs per PCP relative to non
      PCMHs. The ratios of NPs to PCPs were almost twice as high in PCMHs compared with
      non-PCMHs (0.20 and 0.11), and ratios were similarly different for PAs to PCPs
      (0.16 and 0.09, respectively). The multivariate analyses also support that higher
      NP and PA staffing was associated with PCMH designation (i.e., there was one
      additional NP and/or PA for every 25 PCPs). DISCUSSION: The growth of PCMHs may
      require more NPs and PAs to meet the anticipated growth in demand for health
      care. Policy- and practice-level changes are necessary to use them in the most
      effective ways.

PMID- 26211844
TI  - Using clinical genomics in health care: Strategies to create a prepared
      workforce.

PMID- 26211845
TI  - Understanding placebo effects: Implications for nursing practice.
AB  - Placebo effects permeate many aspects of the clinical environment. However,
      little attention has been devoted to placebo effects in the nursing literature.
      Recent research shows that the promotion of placebo responses can enhance certain
      patient outcomes. Nurses are situated in an ideal position to take on this task.
      This article suggests ways for nurses to ethically promote placebo responses in
      daily practice. 

PMID- 26211846
TI  - Work-life balance of nursing faculty in research- and practice-focused doctoral
      programs.
AB  - OBJECTIVES: The growing shortage of nursing faculty and the need for faculty to
      teach doctoral students to address the shortage call for examination of factors
      that may contribute to the shortage, including those that are potentially
      modifiable, including work-life balance.This descriptive study examined work-life
      balance of a national sample of nursing faculty teaching in research-focused and
      practice-focused doctoral programs. METHODS: Data were collected through an
      online survey of 554 doctoral program faculty members to identify their
      perceptions of work-life balance and predictors of work-life balance. RESULTS:
      Work-life balance scores indicated better work-life balance than expected.
      Factors associated with good work-life balance included higher academic rank,
      having tenure, older age, years in education, current faculty position, and no
      involvement in clinical practice. Current faculty position was the best predictor
      of work-life balance. CONCLUSIONS: Although work-life balance was viewed
      positively by study participants, efforts are needed to strengthen factors
      related to positive work/life in view of the increasing workload of doctoral
      faculty as the numbers of doctoral students increase and the number of seasoned
      faculty decrease with anticipated waves of retirements.

PMID- 26211847
TI  - Commonalities of nurse-designed models of health care.
AB  - The American Academy of Nursing has identified examples of care redesign
      developed by nurses who address the health needs of diverse populations. These
      models show important clinical and financial outcomes as summarized in the Select
      Edge Runner Models of Care table included in this article. A study team appointed
      by the Academy explored the commonalities across these models. Four commonalities
      emerged: health holistically defined; individual-, family-, and community-centric
      approaches to care; relationship-based care that enables partnerships and builds
      patient engagement and activation; and a shift from episodic individual care to
      continuous group and public health approaches. The policy implications include
      examining measures of an expanded definition of health, paying for visionary
      care, and transparency and rewards for community-level engagement. 

PMID- 26211848
TI  - Effect of acute systemic hypoxia on human cutaneous microcirculation and
      endothelial, sympathetic and myogenic activity.
AB  - The regulation of cutaneous vascular tone impacts vascular vasomotion and blood
      volume distribution as a challenge to hypoxia, but the regulatory mechanisms yet
      remain poorly understood. A skin has a very compliant circulation, an increase in
      skin blood flow results in large peripheral displacement of blood volume, which
      could be controlled by local and systemic regulatory factors. The aim of this
      study was to determine the acute systemic hypoxia influence on blood flow in
      skin, local regulatory mechanism fluctuations and changes of systemic hemodynamic
      parameters. Healthy subjects (n=11; 24.9+/-3.7years old) participated in this
      study and procedures were performed in siting position. After 20min of
      acclimatization 15min of basal resting period in normoxia (pO2=21%) was recorded,
      followed by 20min in acute systemic hypoxia (pO2=12%), and after 15min of
      recovery period in normoxia (pO2=21%). HRV was used to evaluate autonomic nervous
      system activity to heart from systemic hemodynamic parameters which continuously
      evaluated cardiac output, total peripheral resistance and mean arterial blood
      pressure. Regional blood flow was evaluated by venous occlusion plethysmography
      and skin blood flow by laser-Doppler flowmetry. To evaluate local factor
      influences to cutaneous circulation wavelet analysis was used; fluctuations in
      the frequency intervals of 0.0095-0.021, 0.021-0.052, and 0.052-0.145Hz
      correspondingly represent endothelial, sympathetic, and myogenic activities. Our
      results from HRV data suggest that acute systemic hypoxia causes statistically
      significant increase of sympathetic (LF/HF; N1=0.46+/-0.25 vs. H=0.67+/-0.36;
      P=0.027) and decrease of parasympathetic (RMSSD; 80.0+/-43.1 vs. H=69.9+/-40.4,
      ms; P=0.009) outflow to heart. Acute hypoxia causes statistically significant
      increase of heart rate (RR interval; N1=960.3+/-174.5 vs. H=864.7+/-134.6, ms;
      P=0.001) and cardiac output (CO; N1=5.4 (5.2; 7.9) vs. H=6.7+/-1.4, l/min;
      P=0.020). Regional blood flow and vascular conductance were not changed during
      acute systemic hypoxia, but forearm skin blood flow (skin blood flow; N1=39.7
      (34.0; 53.2) vs. H=51.6+/-13.9, PU; P=0.002) increases however local regulatory
      factor activity was not changed by acute systemic hypoxia. Acute systemic hypoxia
      causes sympathetic stimulation to heart which results in increased heart rate and
      larger cardiac output which could be the reason of forearm skin blood flow
      increase in acute systemic hypoxia without impact of local regulatory factors. 

PMID- 26211849
TI  - On the capillary pressure function in porous media based on relative
      permeabilities of two immiscible fluids: Application of capillary bundle models
      and validation using experimental data.
AB  - The objective of the current paper is to extend the theoretical approach and an
      analytical solution, which was proposed by Babchin and Faybishenko (2014), for
      the evaluation of a capillary pressure (Pc) curve in porous media based on the
      apparent specific surface area, using an explicit combination of the relative
      permeability functions for the wetting and nonwetting phases. Specifically, in
      the current paper, the authors extended this approach by the application of two
      types of capillary bundle models with different formulations of effective
      capillary radius formulae. The application of the new models allowed the authors
      to improve the results of calculations of the effective average contact angle
      given in the paper by Babchin and Faybishenko (2014). The validation of the new
      models for calculations of the Pc curve is also given in this paper using the
      results of a specifically designed core experiment, which was originally
      conducted by Ayub and Bentsen (2001). 

PMID- 26211850
TI  - Revision Rate and Patient-Reported Outcome After Hip Resurfacing Arthroplasty: A
      Concise Follow-Up of 1064 Cases.
AB  - We investigated survival and outcomes in 1064 HRA hips operated on between 1998
      and 2009. After a mean of 7.8 years, 771 patients (72.4%) completed
      questionnaires, with a further 160 (15.0%) contacted by phone and 18 (1.7%) had
      died. There were 54 revisions. Overall implant survival at 10 years was 94.4%.
      Independent predictors of lower survival were female gender (P=0.015) and cup
      inclination >=55 degrees  (P<0.001). Woman with cup inclination >=55 degrees  had
      the highest failure rate with 10-year survival of 69.3%. Vertical cup inclination
      >=55 degrees  did worse than cups <55 degrees  in both men and women. Overall men
      did better than women, and men with cups <55 degrees did best. Men had
      significantly better patient-reported outcome scores than woman.

PMID- 26211851
TI  - Surgical Resident Education in Noninstrumented Lumbar Spine Surgery: A
      Prospective Observational Study with a 4.5-Year Follow-Up.
AB  - OBJECTIVE: To review the outcomes of noninstrumented lumbar spine surgery
      performed by trainees as primary operators versus the outcomes of surgery
      performed by board-certified faculty neurosurgeons. METHODS: This prospective
      observational study involved patients undergoing noninstrumented surgery for
      lumbar disc herniation or lumbar spinal stenosis with a 4.5-year follow-up.
      Teaching cases (patients were operated on by neurosurgical residents in training)
      and nonteaching cases (patients were operated on by board-certified faculty
      neurosurgeons) were reviewed. Back and leg pain on a visual analog scale,
      functional disability using the Roland Morris Disability Questionnaire and
      Oswestry Disability Index, and health-related quality of life (HRQOL) using the
      12-Item Short Form Survey and EuroQol 5D were assessed, and reoperations since
      the index surgery were recorded. RESULTS: Questionnaires were returned by 30
      patients operated on by residents and 74 patients operated on by board-certified
      faculty neurosurgeons. On the 12-Item Short Form Survey physical component scale
      metric, teaching cases were 70% as likely as nonteaching cases (odds ratio =
      0.70, 95% confidence interval = 0.25-1.98, P = 0.585) to achieve a favorable
      HRQOL response to surgery. Visual analog scale measures of back and leg pain were
      similar for teaching and nonteaching cases. The same was true for functional
      disability as measured by the Roland Morris Disability Questionnaire and Oswestry
      Disability Index and for HRQOL measured by the EuroQol 5D. The reoperation rate
      4.5 years after the index surgery was also similar for both groups (~ 10% for
      both groups). CONCLUSIONS: The global outcome, as measured by HRQOL response
      after a mean follow-up of 4.5 years, was similar for teaching and nonteaching
      cases. Patients from both groups scored virtually equal results on various pain,
      functional, and HRQOL metrics, and the reoperation rate was similar.

PMID- 26211853
TI  - Dr. Lenke Horvath (1917-1991): Creator of Pediatric Neurosurgery in Romania.
AB  - The development of neurosurgery as an independent specialty took place with great
      difficulty in Romania. In this respect, the most revered personalities are those
      of Professor Alexandru Moruzzi (1900-1957) (in Iasi) and Professor Dimitrie
      Bagdasar (1893-1946) (in Bucharest), who are the fathers of modern neurosurgery
      in Romania. Professor Bagdasar was schooled in Professor Harvey Cushing's clinic
      in Boston and is credited with creating the first completely independent
      neurosurgical unit in Romania. His legacy was carried on with honor by Professor
      Constantin Arseni (1912-1994), who, in 1975, tasked Dr. Lenke Horvath (1917-1991)
      with creating the first autonomous pediatric neurosurgery unit in Bucharest. This
      article is a small tribute to the founder of pediatric neurosurgery in Romania
      and one of the female pioneer neurosurgeons, who, by personal example of
      dedication and hard work, radically changed medical thinking and neurosurgery in
      Romania. 

PMID- 26211852
TI  - Importance of IL-6, MMP-1, IGF-1, and BAX Levels in Lumbar Herniated Disks and
      Posterior Longitudinal Ligament in Patients with Sciatic Pain.
AB  - PURPOSE: The aim of this study was to evaluate prognostic importance of
      interleukin-6 (IL-6), matrix metalloproteinase (MMP)-1, insulin-like growth
      factor (IGF)-1, and Bcl-2-associated X protein (BAX) levels in biopsy specimens
      taken from the intervertebral disk specimens and the posterior longitudinal
      ligaments of patients with sciatic pain. METHODS: The specimens of the
      intervertebral disk and the posterior longitudinal ligament were obtained from 52
      patients undergoing herniectomy and diskectomy at the Neurosurgery Department of
      the Abant Izzet Baysal University Izzet Baysal Training and Research Hospital
      between April 2012 and February 2014. The immunohistochemical expressions of IL
      6, MMP-1, IGF-1, and BAX were evaluated in three categories: mild, moderate, and
      intense. RESULTS: The IL-6 expression in the intervertebral disk specimens was
      intense in the sequestration group when compared with that of the "protrusion"
      and "extrusion" groups. The intervertebral disk specimens in "extrusion" and
      "sequestration" groups were stained intensely for MMP-1. The IGF-1 expression was
      stained intensely in the intervertebral disk tissue of the extrude group
      patients. For the "extrusion" and "sequestration" groups, the intervertebral disk
      specimens were stained intensely for BAX compared with the protrude group. The IL
      6 expression in the posterior longitudinal ligament specimens was more intense in
      the "sequestration" and "extrusion" groups when compared with that of the
      protrude group. The MMP-1 expressions were milder in the sequestration group when
      compared with that of the "extrusion" and "protrusion" groups. CONCLUSIONS: Our
      findings suggest that the cytokines, enzymes, growth factors, and proapoptotic
      proteins, such as IL-6, MMP-1, IGF-1, and BAX, may be critical factors in the
      pathophysiology of the degeneration of the intervertebral disks in patients with
      symptomatic degenerative disk disease.

PMID- 26211854
TI  - Microsurgical Treatment of Posterior Cerebral Circulation Aneurysms Via Keyhole
      Approaches.
AB  - OBJECTIVE: To explore the techniques of microsurgical treatment for posterior
      cerebral circulation aneurysms via keyhole approaches and assess its feasibility.
      METHODS: A total of 27 patients with 28 posterior cerebral circulation aneurysms
      were treated surgically by keyhole approaches; 24 patients presented with
      subarachnoid hemorrhage and 3 with headache. Of these 27 patients, 15 patients
      were treated via the supraorbital keyhole approach, 6 via the retrosigmoid
      keyhole approach, 3 via the subtemporal keyhole approach, 2 via median
      suboccipital approach, and 1 via the pterional keyhole approach. RESULTS: Of the
      28 posterior cerebral circulation aneurysms, 24 aneurysms were clipped and 4
      trapped; 23 aneurysms clipped completely, and 1 had residual aneurysm. Glasgow
      Outcome Scores at discharge revealed 25 patients had a good recovery; 1 patient
      was slightly disabled, and 1 patient was severely disabled. Of 15 patients
      treated via the supraorbital keyhole approach, to make a wider operative space,
      drilling of anterior clinoid process (2 patients) and posterior clinoid process
      (3 patients) was performed; posterior communicating artery was cut off (1
      patient). For 3 patients with multiple aneurysms, complete occlusion was achieved
      via the same approach at one-stage. CONCLUSIONS: Individualized keyhole
      approaches for posterior cerebral circulation artery aneurysms are safe and
      effective. The anterior clinoid process or posterior clinoid process could be
      drilled to offer a wide operative space for clipping. The use of multiple working
      windows is very helpful for controlling the parent artery and clipping the
      aneurysm.

PMID- 26211855
TI  - Health Literacy and Pseudoliteracy in Neurosurgery: the "C. Besta" Experience.

PMID- 26211856
TI  - Effectiveness of Postoperative Gamma Knife Radiosurgery to the Tumor Bed After
      Resection of Brain Metastases.
AB  - OBJECTIVE: The role of Gamma knife radiosurgery (GKS) after the resection of
      brain metastases remains undefined. We evaluated the outcomes of postoperative
      GKS to the tumor bed after the resection of brain metastasis compared with GKS
      alone without resection in the same patients. METHODS: We performed a
      retrospective review of 24 patients who underwent GKS to the tumor bed after the
      resection of brain metastases. In this cohort, 25 metastatic lesions were treated
      with postoperative GKS, and 37 brain metastatic lesions were simultaneously
      managed with GKS alone without resection. RESULTS: The median target volume and
      marginal dose of GKS to the surgical bed were 10.5 cm(3) and 15.0 Gy,
      respectively. The median target volume and marginal dose of GKS alone for the
      metastatic lesions were 0.5 cm(3) and 21.0 Gy, respectively. The actuarial 1-year
      and 2-year overall survival of the patients were 43.1% and 28.7%, respectively.
      The median overall survival of all patients was 11 months. The actuarial 6-month
      and 12-month local progression-free survival of GKS alone for metastatic lesions
      without resection were 92.6% and 84.9%; however, the actuarial 6-month and 12
      month local progression-free survival of GKS to the surgical bed were 82% and
      71%, respectively. CONCLUSIONS: For patients with brain metastases treated with
      surgical resection, postoperative GKS to the resection area is an effective and
      safe treatment option. Particularly, concurrent postoperative GKS to the surgical
      cavity with GKS alone for multiple small metastatic lesions is a feasible
      treatment strategy for multiple brain metastases.

PMID- 26211857
TI  - Helmet Use and Traumatic Brain Injury in Snowboarding.

PMID- 26211858
TI  - Assessment of patients with nasal polyposis by the neutrophil-to-lymphocyte ratio
      and eosinophil-to-lymphocyte ratio.
AB  - OBJECTIVES: This study aims to investigate the neutrophil-to-lymphocyte ratio
      (NLR) and eosinophil-to-lymphocyte ratio (ELR) levels in recurrent and non
      recurrent nasal polyposis, and identify how the NLR and ELR reflect the
      inflammatory status in this specific diagnosis preoperatively. PATIENTS AND
      METHODS: A total of 158 patients (102 males, 56 females; mean age 29.40+/-5.44
      years; range 14 to 48 years) were included in the study. The patients were
      divided into two groups: group 1 included 80 recurrent nasal polyposis patients
      (44 males, 36 females; mean age 30.0+/-9.4 years; range 14 to 47 years) and group
      2 included 78 non-recurrent nasal polyposis patients without allergic or atopic
      backgrounds (58 males, 20 females; mean age 28.8+/-10.1 years; range 17 to 48
      years). The NLR and ELR values for each patient were calculated from the complete
      blood counts taken before surgery. The values of preoperative white blood cell,
      neutrophil, lymphocyte, eosinophil, NLR and ELR were compared for each group, and
      also in between the two groups. RESULTS: The preoperative neutrophil, eosinophil,
      NLR and ELR values of group 1 were significantly higher than group 2 (p=0.042,
      p=0.013, p=0.019, and p=0.0001 respectively). CONCLUSION: Neutrophil-to
      lymphocyte and ELR measurements can be used effectively in patients with nasal
      polyposis as an auxiliary method in deciding for the necessity of recurrence
      follow-ups.

PMID- 26211859
TI  - Prevalence of otitis media with effusion among school age children in rural parts
      of Konya province, Turkey.
AB  - OBJECTIVES: This study aims to evaluate the current prevalence of serous otitis
      media (SOM) among school age children living in rural areas of Konya province
      located in southern Turkey. PATIENTS AND METHODS: This cross sectional study
      which was conducted between October 2012 and January 2013 included 2,352 children
      (1,179 males, 1,173 females; mean age 8.9+/-2.8 years; range 4 to 15 years) who
      attended 36 different primary schools in rural parts of the Konya province.
      Otologic complaints, findings, and tympanometry results were recorded. Diagnosis
      of SOM was obtained based on history, symptoms, abnormal otoscopy and tympanogram
      findings. RESULTS: The overall prevalence of SOM was 4.6%. The highest prevalence
      was at the age of four (11.2%). There was a significantly higher prevalence of
      SOM at the age of six (11.1%). The overall prevalence was higher in males (6.17%)
      compared to females (3.16%) in all age groups (p<0.05). CONCLUSION: Compared to
      the literature, overall prevalence of SOM in our study was lower. Development of
      preventive and therapeutic strategies in the first step health care service may
      have a considerable effect on this low rate.

PMID- 26211860
TI  - Parathyroid scintigraphy and minimal invasive surgery in parathyroid adenomas.
AB  - OBJECTIVES: This study aims to identify the diagnostic capacity of the technetium
      99m sestamibi scintigraphy with single photon emission computed tomography for
      localizing parathyroid pathologies. PATIENTS AND METHODS: Data of 13 patients (4
      males, 9 females; mean age 49.23 years; range 27 to 63 years) who had minimally
      invasive parathyroidectomy due to primary hyperparathyroidism at the Haseki
      Training and Research Hospital Ear-Nose-Throat clinic between January 2013 and
      December 2013 were retrospectively analyzed. Two patients were excluded due to
      incomplete documentation. RESULTS: Mean preoperative parathyroid hormone and
      calcium levels were 284.36 (134-1,083 pg/mL) and 11.9 (10.7-13.5 mg/dL),
      respectively. The operation was deemed adequate if intraoperative parathyroid
      hormone dropped by 50% from the preoperative level or frozen section analysis
      showed hypercellular gland or adenoma. Only sestamibi scintigraphy results were
      consistent with focal exploration findings in all patients. Focal exploration and
      parathyroid adenoma excision via minimally invasive parathyroidectomy were
      successfully carried out in 10 patients with single adenoma confirmed by
      sestamibi. CONCLUSION: Technetium 99m sestamibi scintigraphy with single photon
      emission computed tomography and frozen section analysis may provide more
      meaningful information and be more advantageous compared to other preoperative
      localization techniques.

PMID- 26211862
TI  - Effects of sleep bruxism related tinnitus on quality of life.
AB  - OBJECTIVES: This study aims to analyze the subjective and objective
      characteristics of tinnitus in sleep bruxism patients. PATIENTS AND METHODS: The
      study included 57 patients (12 males; 45 females; mean age 33.89+/-12.50 years;
      range 19 to 55 years) with sleep bruxism and tinnitus (sleep bruxism group) and
      24 patients (6 males, 18 females; mean age 43.75+/-16.19 years; range 21 to 58
      years) only with tinnitus (control group). Sleep bruxism was diagnosed by the
      diagnostic criteria of American Academy of Sleep Medicine. Patients were
      performed pure tone audiometry to detect hearing thresholds at standard and high
      frequencies. Tinnitus frequency and loudness were assessed. Subjective aspects of
      tinnitus were identified by tinnitus handicap inventory. RESULTS: The statistical
      analysis revealed that the sleep bruxism group had significantly lower hearing
      thresholds except 1000 Hz and 2000 Hz. Tinnitus frequency was between 3000 Hz and
      18000 Hz in sleep bruxism group while it was between 6000 and 16000 Hz in control
      group with no statistically significant difference (p=0.362). Sleep bruxism group
      had significantly lower tinnitus loudness and tinnitus handicap inventory scores
      in comparison to control group (p=0.024 and p=0.000, respectively). CONCLUSION:
      Tinnitus caused by sleep bruxism and temporomandibular joint issues has higher
      frequency and lower loudness compared to patients with only tinnitus.

PMID- 26211861
TI  - Foreign body impaction in esophagus: experiences at Ear-Nose-Throat Clinic in
      Tuzla, 2003-2013.
AB  - OBJECTIVES: This study aims to report our experience in the management of foreign
      body (FB) impaction in esophagus in the Ear-Nose-Throat Clinic, University
      Clinical Center of Tuzla, Bosnia and Herzegovina. PATIENTS AND METHODS: Seventy
      one patients (44 males, 27 females; mean age 32.99+/-28.57 years; range 1 to 81
      years) who admitted to our clinic between January 2003 and December 2013 with a
      history of a FB in esophagus were retrospectively analyzed including head and
      neck examination. All patients were performed rigid esophagoscopy under general
      anesthesia. RESULTS: A total of 32 FBs were detected in children (23 males, 9
      females; mean age 4.6 years; range 1 to 11, mod 1) with coins being the most
      common (56.31%). A total of 39 FBs were detected in adults (21 males, 18 females;
      mean age 56.2 years; range 16 to 81) with bones and food being the most common
      (43.6%). Foreign bodies impacted in the upper esophageal sphincter in 87.5% of
      children and in 66.7% of adults. The duration of localization of FBs in esophagus
      was between one hour and six months. All procedures were performed without
      complications; the FBs were completely extracted without the requirement to
      repeat the procedure. CONCLUSION: Our study results suggest that use of rigid
      endoscope is reliable in removing FBs in the esophagus.

PMID- 26211863
TI  - [Our surgical treatment results in pediatric cholesteatoma].
AB  - OBJECTIVES: This study aims to evaluate surgical techniques and obtained outcomes
      in pediatric cholesteatoma. PATIENTS AND METHODS: A total of 62 patients (41
      males, 21 females; mean age 13 years; range 3 to 17 years) diagnosed as pediatric
      cholesteatoma between January 1998 and December 2014 were enrolled into the
      study. Of the patients, canal wall down (CWD) mastoidectomy was performed in 31,
      canal wall up (CWU) mastoidectomy in 13, inside-out (ISO) mastoidectomy in eight,
      and tympanoplasty in 10. Surgical approaches, staging, hearing outcomes, relapse
      status, and surgical data were retrospectively analyzed. RESULTS: Cholesteatoma
      recurred in seven patients (11%). Recurrence rates for CWU and CWD
      mastoidectomies were 31% and 6%, respectively. While the number of patients with
      good serviceable hearing (pure-tone average >=25 dB) was 10 preoperatively, it
      became 16 postoperatively. Ossicular erosion was higher in CWD group. Twenty-nine
      patients (47%) had extensive disease and CWD mastoidectomy was performed in 86%
      of these. Number of patients not requiring care was 45 (72.6%). CONCLUSION: In
      this study, we observed no differences in terms of good serviceable hearing
      between CWU and CWD mastoidectomies. The preferred method was mainly CWD in
      patients with extensive disease and ossicular erosion. Recurrence rates were
      higher in CWU group. Therefore, ISO or CWD mastoidectomy come to the forefront as
      appropriate treatment options in the treatment of pediatric cholesteatomas
      according to the extensiveness of disease.

PMID- 26211864
TI  - A large schwannoma of external auditory canal: an unusual case.
AB  - A 49-year-old female patient presented with mass occluding her external auditory
      meatus. Surgical exploration revealed that the mass eroded the bony canal wall
      and biopsy reported the mass as a schwannoma. Schwannoma should be considered in
      the differential diagnosis of a soft tissue swelling arising from the external
      auditory canal. 

PMID- 26211865
TI  - Multiple primary malignant paraganglioma of the head and neck with lymph node
      metastasis.
AB  - Paragangliomas of the head and neck are usually benign tumors. Malignant form is
      quite rare and criteria for malignancy are not clear. Clinical, biochemical and
      histological features of malignant forms are not sufficient to reliably
      distinguish them from benign tumors and malignancy is established only in the
      presence of distant metastasis. Herein, we report a patient with glomus jugulare
      on the right, glomus vagale and glomus caroticum tumors on the left side with
      cervical lymph node metastasis on the right side. 

PMID- 26211866
TI  - Unusual foreign body in the larynx: a bee.
AB  - Foreign body lodgement in the larynx is a rare situation. Our review of the
      literature revealed no living foreign body in larynx except for laryngeal leeches
      and anisakiasis. In this article, we report a patient with unusual laryngeal
      foreign body lodgement: a bee which presented with sudden odynophagia and
      stinging sensation in throat. The bee was detected on the laryngeal mucosa in
      indirect laryngoscopic examination and removed immediately under general
      anesthesia in apneic period. In this case report, we describe the importance of
      detailed anamnesis and laryngeal examination even if the patient has no severe
      symptoms. 

PMID- 26211867
TI  - An unusual mass of nasal cavity: recurrent glomangiopericytoma.
AB  - Hemangiopericytomas are rare tumors of sinonasal region. In this article, we
      described a case of recurrent mass in right nasal cavity which presented with
      nasal obstruction and intermittent epistaxis. Patient had a surgical history on
      the same nasal region without any histopathological document. Abnormal bleeding
      was observed during surgery and mass was partially removed for histopathological
      investigation. The result was glomangiopericytoma of the sinonasal region.
      Although extended surgery was recommended to the patient including preoperative
      and perioperative measures for bleeding problem, patient preferred to follow-up
      rather than removal. The clinical progress and review of glomangiopericytoma have
      also been discussed. 

PMID- 26211868
TI  - Malignant eccrine spiradenoma of the external ear.
AB  - Eccrine spiradenoma is a benign tumor of sweat gland origin. Malignant eccrine
      spiradenoma is a rare neoplasm which almost always arises from a pre-existing
      spiradenoma lesion. In this article, we present a patient with malignant eccrine
      spiradenoma of the auricula with a prior diagnosis as benign eccrine spiradenoma.
      Although malignant transformation is usually associated with aggressive behavior,
      we did not detect recurrence or metastasis in four years of follow-up after
      performing wide excision. 

PMID- 26211869
TI  - Atrophic rhinitis caused by Cedecea davisae with accompanying mucocele.
AB  - Atrophic rhinitis is a chronic inflammatory disease characterized by progressive
      atrophy of nasal mucosa. Cedecea davisae, a rare pathogen, is a new member of
      Enterobacteriaceae family. In this article, we report a patient with atrophic
      rhinitis whose culture test revealed Cedecea davisae. The patient was operated
      due to accompanying posterior ethmoid mucocele. Levofloxacin and nasal irrigation
      were administered for two months. Significant improvement was observed in
      patient's complaints and nasal signs at postoperative sixth month. In conclusion,
      Cedecea davisae has been thought to cause atrophic rhinitis and mucocele in this
      patient. Patient recovered with simple treatment. These bacteria should be kept
      in mind as a causative agent for atrophic rhinitis. 

PMID- 26211870
TI  - High intensity focused ultrasound for the treatment of advanced liver cancer.

PMID- 26211872
TI  - Pancreatic exocrine insufficiency in pancreatic cancer: A review of the
      literature.
AB  - Pancreatic exocrine insufficiency is a well-documented complication of chronic
      pancreatitis; however, study results of pancreatic exocrine insufficiency in
      pancreatic cancer are less consistent. This applies for patients who are treated
      non-surgically and those who undergo curative pancreatic cancer resection. This
      review article summarizes relevant studies addressing pancreatic exocrine
      insufficiency in pancreatic cancer, with particular differentiation between non
      surgically and surgically treated patients, as well as between the different
      surgeries. We also summarize studies addressing pancreatic enzyme replacement
      therapy in pancreatic cancer. 

PMID- 26211871
TI  - Visceral fat area predicts survival in patients with advanced hepatocellular
      carcinoma treated with tyrosine kinase inhibitors.
AB  - BACKGROUND: Anthropometric measurements have been linked to resistance to anti
      angiogenic treatment and survival. METHODS: Patients with advanced hepatocellular
      carcinoma treated with sorafenib or brivanib in 2008-2011 were included in this
      retrospective study. Anthropometric measurements were assessed using computed
      tomography and were correlated with drug toxicity, radiological response, and
      overall survival. RESULTS: 52 patients were included, Barcelona Clinic Liver
      Classification B (38%) and C (62%), with a mean value of alpha-fetoprotein of
      29,554+/-85,654 ng/mL, with a median overall survival of 10.5 months. Sarcopenia
      was associated with a greater rate of hand-foot syndrome (P=0.049). Modified
      Response Evaluation Criteria In Solid Tumours (mRECIST) and Choi criteria were
      significantly associated with survival, but RECIST criteria were not. An absence
      of hand-foot syndrome and high-visceral fat area were associated with progressive
      disease as assessed by RECIST and mRECIST criteria. In multivariate analyses,
      high visceral fat area (HR=3.6; P=0.002), low lean body mass (HR=2.4; P=0.015),
      and presence of hand-foot syndrome (HR=1.8; P=0.004) were significantly
      associated with overall survival. In time-dependent multivariate analyses; only
      high visceral fat area was associated with survival. CONCLUSION: Visceral fat
      area is associated with survival and seems to be a predictive marker for primary
      resistance to tyrosine kinase inhibitors in patients with advanced hepatocellular
      carcinoma.

PMID- 26211873
TI  - Familiarity for famous faces and names is not equally subtended by the right and
      left temporal poles. Evidence from an rTMS study.
AB  - The aims of the present experiment was to investigate: (a) if transient
      disruption of neural activity in the right (RTP) or left temporal pole (LTP) can
      interfere with the development of a familiarity feeling to the presentation of
      faces/written names of famous/unknown people; and (b) if this interference
      specifically affects the familiarity for faces after inhibition of the RTP and
      for names after inhibition of the LTP. Twenty healthy volunteers took part in the
      study. Repetitive transcranial magnetic stimulation (rTMS) was administered
      online; it disrupted the neural activity of the right or left TP in concomitance
      with the presentation of each face and name whose familiarity had to be assessed.
      Furthermore, in a control group, each participant was submitted to a single
      experimental session in which rTMS was delivered to the vertex in association
      with the presentation of faces and written names. Since previous rTMS studies
      have shown that the temporary inactivation of the right and left TP influences
      the response latencies, but not the number of correct responses, in this study we
      took into account both the number of correct responses obtained in different
      experimental conditions and the corresponding response latencies. A three-way
      factorial ANOVA carried out on the Response Scores showed only a general effect
      of the Type of Stimuli, due to better performances on names than on faces. This
      greater familiarity of names is consistent with previous data reported in the
      literature. In the three-way factorial ANOVA carried out on the Latency Scores,
      post-hoc analyses showed an increased latency of responses to faces after right
      stimulation in Latency Total, Latency on Correct responses and Latency on
      Unfamiliar faces. None of these results were obtained in the control group. These
      data suggest that rTMS at the level of the RTP preferentially affects the
      development of familiarity feelings to the presentation of faces of famous
      people. 

PMID- 26211875
TI  - Electrode kinetics of the NiO porous electrode for oxygen production in the
      molten carbonate electrolysis cell (MCEC).
AB  - The performance of a molten carbonate electrolysis cell (MCEC) is to a great
      extent determined by the anode, i.e. the oxygen production reaction at the porous
      NiO electrode. In this study, stationary polarization curves for the NiO
      electrode were measured under varying gas compositions and temperatures. The
      exchange current densities were calculated numerically from the slopes at low
      overpotential. Positive dependency on the exchange current density was found for
      the partial pressure of oxygen. When the temperature was increased in the range
      600-650  degrees C, the reaction order of oxygen decreased from 0.97 to 0.80.
      However, there are two different cases for the partial pressure dependency of
      carbon dioxide within this temperature range: positive values, 0.09-0.30, for the
      reaction order at lower CO2 concentration, and negative values, -0.26-0.01, with
      increasing CO2 content. A comparison of theoretically obtained data indicates
      that the oxygen-producing reaction in MCEC could be reasonably satisfied by the
      reverse of oxygen reduction by the oxygen mechanism I, an n = 4 electron
      reaction, assuming a low coverage of oxide ions at high CO2 content and an
      intermediate coverage for a low CO2 concentration. 

PMID- 26211874
TI  - Deceivingly dynamic: Learning-dependent changes in stathmin and microtubules.
AB  - Microtubules, one of the major cytoskeletal structures, were previously
      considered stable and only indirectly involved in synaptic structure and function
      in mature neurons. However, recent evidence demonstrates that microtubules are
      dynamic and have an important role in synaptic structure, synaptic plasticity,
      and memory. In particular, learning induces changes in microtubule turnover and
      stability, and pharmacological manipulation of microtubule dynamics alters
      synaptic plasticity and long-term memory. These learning-induced changes in
      microtubules are controlled by the phosphoprotein stathmin, whose only known
      cellular activity is to negatively regulate microtubule formation. During the
      first eight hours following learning, changes in the phosphorylation of stathmin
      go through two phases causing biphasic shifts in microtubules
      stability/instability. These shifts, in turn, regulate memory formation by
      controlling in the second phase synaptic transport of the GluA2 subunit of AMPA
      receptors. Improper regulation of stathmin and microtubule dynamics has been
      observed in aged animals and in patients with Alzheimer's disease and depression.
      Thus, recent work on stathmin and microtubules has identified new molecular
      players in the early stages of memory encoding. 

PMID- 26211876
TI  - Association of OCT4, SOX2, and NANOG expression with oral squamous cell carcinoma
      progression.
AB  - BACKGROUND: OCT4, SOX2, and NANOG are major transcription factors related to stem
      cell self-renewal and differentiation. The aim of this study was to examine the
      association of OCT4, SOX2, and NANOG expression levels with the development and
      prognosis of patients with oral squamous cell carcinoma (OSCC). MATERIALS AND
      METHODS: Expression levels of OCT4, SOX2, and NANOG were evaluated by
      immunohistochemistry with tissue microarray slides of 436 OSCC, 362 corresponding
      tumor-adjacent normal (CTAN) tissues, and 71 normal uvula epithelium tissues. The
      clinicopathologic and follow-up data of the OSCC patients were recorded. RESULTS:
      OCT4 expression was significantly higher in normal and CTAN tissues than in tumor
      tissue (both P < 0.001). SOX2 expression in CTAN tissue was significantly higher
      than that in normal (P = 0.021) and tumor tissues (P < 0.001). However, NANOG
      expression was significantly higher in CTAN (P = 0.014) and tumor tissues (P =
      0.009) than in normal tissue. Higher OCT4 and SOX2 expressions were associated
      with earlier AJCC stage (P = 0.002 and P < 0.001), small tumor size (P = 0.017
      and P = 0.001), and the absence of lymph node metastasis (P = 0.015 and P =
      0.025). Higher levels of SOX2 expression were associated with better disease
      specific survival (P = 0.002) even after adjustment for clinicopathologic
      factors. DISCUSSION: OCT4 and SOX2 are biomarkers of tumorigenesis and early
      stage OSCC. SOX2 is an independent prognostic factor for OSCC.

PMID- 26211877
TI  - Two new phenolic compounds from the leaves of Alnus sibirica Fisch. ex Turcz.
AB  - Two new phenolic compounds, 4-O-glucopyranosyl-5-O-caffeoylshikimic acid (1) and
      2,3-digalloyl oregonin (2), were isolated along with eight known phenolic
      compounds (3-10) from an 80% acetone extract of Alnus sibirica leaves. The
      chemical structures of these compounds were elucidated using 1D/2D nuclear
      magnetic resonance and high resolution-MS. The anti-oxidative activities of these
      compounds were determined by assaying their 1,1-diphenyl-2-picrylhydrazyl radical
      and nitroblue tetrazolium superoxide anion scavenging activity. All of the
      isolated phenolic compounds (1-10) exhibited potent anti-oxidative activities. In
      particular, 2 and 4, which are diarylheptanoids, and 10 which is ellagitannin
      exhibited excellent anti-oxidative activities with almost the same potency as
      that of the positive controls L-ascorbic acid and allopurinol.

PMID- 26211878
TI  - Totally laparoscopic living donor right hepatectomy in a donor with trifurcation
      of bile duct.
AB  - Donor operation in adult living donor liver transplantation is associated with
      significant postoperative morbidity. To avoid laparotomy wound complications and
      shorten postoperative recovery, laparoscopic liver graft harvest has been
      developed recently. However, to determine the cut point of bile duct is
      challenging. Herein, we report the application of totally laparoscopic approach
      for right liver graft harvest in a donor with trifurcation of the bile duct. A19
      year-old man volunteered for living donation to his father who suffered from
      hepatitis B virus-related cirrhosis of liver and hepatocellular carcinoma. The
      graft was 880 mL with a single right hepatic artery and portal vein. The graft to
      recipient weight ratio was 1.06. The middle hepatic vein was preserved for the
      donor and the liver remnant was 42.3%. Two branches of middle hepatic veins were
      > 5 mm in diameter and needed reconstruction with cryopreserved allograft.
      Ductoplasty using laparoscopic intracorporeal suture technique was done to
      achieve single orifice of the graft bile duct. The postoperative course was
      uneventful for the donor. This report adds evidence of the feasibility of pure
      laparoscopic right donor hepatectomy and describes the necessary steps for bile
      duct division in donors with trifurcation of bile duct.

PMID- 26211879
TI  - Using cognitive behaviour therapy with South Asian Muslims: Findings from the
      culturally sensitive CBT project.
AB  - It has been suggested that cognitive behaviour therapy (CBT) needs adaptation for
      it to be effective for patients from collectivistic cultures, as currently CBT is
      underpinned by individualistic values. In prior studies we have demonstrated that
      CBT could be adapted for Pakistani patients in Southampton, UK, and for local
      populations in Pakistan. Findings from these studies suggest that CBT can be
      adapted for patients from collectivistic cultures using a series of steps. In
      this paper we focus on these steps, and the process of adapting CBT for specific
      groups. The adaptation process should focus on three major areas of therapy,
      rather than simple translation of therapy manuals. These include (1) awareness of
      relevant cultural issues and preparation for therapy, (2) assessment and
      engagement, and (3) adjustments in therapy. We also discuss the best practice
      guidelines that evolved from this work to help therapists working with this
      population. We reiterate that CBT can be adapted effectively for patients from
      traditional cultures. This is, however, an emerging area in psychotherapy, and
      further work is required to refine the methodology and to test adapted CBT. 

PMID- 26211880
TI  - Spatial boundary of urban 'acid islands' in southern China.
AB  - Elevated emissions of sulfur dioxide, nitrogen oxides and ammonia in China have
      resulted in high levels of sulfur and nitrogen deposition, being contributors to
      soil acidification, especially in and near large cities. However, knowledge gaps
      still exist in the way that large cities shape spatial patterns of acid
      deposition. Here, we assessed the patterns of pH, sulfate, nitrate and ammonium
      in bulk precipitation and throughfall in southern China's forests by synthesizing
      data from published literature. Concentrations and fluxes of sulfate, nitrate and
      ammonium in bulk precipitation and throughfall exhibited a power-law increase
      with a closer distance to the nearest large cities, and accordingly pH showed a
      logarithmic decline. Our findings indicate the occurrence of urban 'acid islands'
      with a critical radius of approximately 70 km in southern China, receiving
      potential acid loads of more than 2 keq ha(-1) yr(-1). These urban acid islands
      covered an area of 0.70 million km(2), accounting for nearly 30% of the land area
      in southern China. Despite a significant capacity to neutralize acids in
      precipitation, our analysis highlights a substantial contribution of ammonium to
      potential acid load. Our results suggest a joint control on emissions of multiple
      acid precursors from urban areas in southern China. 

PMID- 26211881
TI  - Decoherence of interacting Majorana modes.
AB  - We study the decoherence of Majorana modes of a fermion chain, where the fermions
      interact with their nearest neighbours. We investigate the effect of dissipation
      and dephasing on the Majorana modes of a fermionic chain. The dissipative and
      dephasing noises induce the non-parity- and parity-preserving transitions between
      the eigenstates of the system, respectively. Therefore, these two types of noises
      lead to the different decoherence mechanisms. In each type of noise, we discuss
      the low- and high-frequency regimes to describe the different environments. We
      numerically calculate the dissipation and dephasing rates in the presence of long
      range interactions. We find that the decoherence rate of interacting Majorana
      modes is different to that of non-interacting modes. We show the examples that
      the long-range interactions can reduce the decoherence rate. It is advantageous
      to the potential applications of quantum information processing. 

PMID- 26211882
TI  - Perinatal outcomes after fresh versus vitrified-warmed blastocyst transfer:
      retrospective analysis.
AB  - OBJECTIVE: To investigate the possible effect of controlled ovarian stimulation
      on the perinatal outcomes of assisted reproductive technology pregnancies, by
      comparing the outcomes from fresh ET with frozen ET (FET) with blastocysts of
      similar quality. DESIGN: Retrospective observational study. SETTING: Private
      fertility center. PATIENT(S): Seven hundred eighty-four fresh transfers and 382
      vitrified-warmed double blastocyst transfers. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Miscarriage, perinatal mortality, preterm delivery, live birth, live
      birth weights, and gestational age of live births. RESULT(S): FET resulted in
      higher implantation rates (51.5% vs. 40.6%), higher live-birth rates per transfer
      (56.8% vs. 44.3%), and lower ectopic pregnancy rates (0.32% vs. 1.80%). FET
      pregnancies also had higher day 14 betahCG levels per implantation (148.2 vs.
      176.2 IU/L) and higher infant birth weights (singletons Delta109.4 g, twins
      Delta124 g). Female infants benefitted the most in terms of birth weight.
      Miscarriage, premature delivery, perinatal morbidity, and live birth per
      pregnancy were all nonsignificantly different between fresh ET and FET.
      CONCLUSION(S): Clinically significant differences between the peri-implantation
      and perinatal outcomes of fresh ET and FET suggest better endometrial receptivity
      and placentation in FET cycles.

PMID- 26211883
TI  - Early-life factors and endometriosis risk.
AB  - OBJECTIVE: To study early-life factors in relation to endometriosis risk in
      adulthood. DESIGN: Population-based case-control study. SETTING: Integrated
      healthcare system. PATIENT(S): Cases (n = 310) were women diagnosed for the first
      time with endometriosis between the years 1996 and 2001, and controls (n = 727)
      were women without a diagnosis of endometriosis randomly selected from the
      healthcare system population. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the
      associations between intrauterine diethylstilbestrol (DES) exposure, maternal
      smoking, mother's age at delivery, firstborn status, birth weight, fetal number,
      prematurity, and regular soy formula feeding during infancy and endometriosis
      were estimated using unconditional logistic regression, adjusting for frequency
      matching and confounding variables. Information on early-life factors was
      ascertained retrospectively by in-person interview, with information on maternal
      DES use and regular soy formula feeding directly gathered from the participant's
      mother or other family member. RESULT(S): We observed that women who were
      regularly fed soy formula as infants had more than twice the risk of
      endometriosis compared with unexposed women (aOR 2.4, 95% CI 1.2-4.9). Our data
      also suggested increased endometriosis risk with prematurity (aOR 1.7, 95% CI 0.9
      3.1) and maternal use of DES (OR 2.0, 95% CI 0.8-4.9, adjusting only for
      frequency matching variables), although these confidence intervals included the
      null. CONCLUSION(S): Our results support the hypothesis that disruption of
      development during fetal and infant periods may increase the risk of
      endometriosis in adulthood.

PMID- 26211884
TI  - Presence of human papillomavirus in semen of healthy men is firmly associated
      with HPV infections of the penile epithelium.
AB  - OBJECTIVE: To study the source of human papillomavirus (HPV) in semen. DESIGN:
      Observational study (CCMO-NL3248800010). SETTING: Academic hospital-based
      laboratory. PATIENT(S): Healthy male volunteers (n = 213). INTERVENTION(S): One
      penile scrape and three semen samples were obtained per participant for HPV-DNA
      testing by both GP5+/6+ polymerase chain reaction (PCR) and SPF10-PCR to detect
      moderate/high and low viral loads, respectively; flat penile lesions (FPL) were
      detected by penoscopy. MAIN OUTCOME MEASURE(S): HPV-DNA presence in semen and
      penile scrapes, and the presence of FPL. RESULT(S): HPV-DNA at moderate/high
      viral loads (i.e., GP5+/6+ PCR-positive) was detected in >=1 semen sample(s) in
      27% of participants. Most men with moderate/high viral loads in the penile scrape
      also had moderate/high viral loads in semen (85%). Men with a HPV-negative penile
      scrape were very unlikely to have moderate/high viral loads in semen (3%). The
      presence of HPV in semen was associated with the presence of HPV in the penile
      scrape also on a genotype-specific level. Having FPL was a risk factor for HPV
      presence in semen. CONCLUSION(S): HPV-DNA presence in semen of healthy men is
      common and associated with HPV infections of the penile epithelium. HPV-DNA
      presence in semen may result from desquamation of HPV-infected penile cells.

PMID- 26211885
TI  - Split thickness skin graft for cervicovaginal reconstruction in congenital
      atresia of cervix.
AB  - OBJECTIVE: To introduce a new technique that combines laparoscopic and vaginal
      cervicovaginal reconstruction using split thickness skin graft in patients with
      congenital atresia of the cervix. DESIGN: Video article introducing a new
      surgical technique. SETTING: University hospital. PATIENT(S): A 16-year-old
      patient with congenital cervical atresia, vaginal dysgenesis, and ovarian
      endometrial cyst. INTERVENTION(S): An original technique of combined laparoscopic
      and vaginal cervicovaginal reconstruction using split thickness skin graft for
      cervicovaginal reconstruction. MAIN OUTCOME MEASURE(S): A midline incision at the
      vaginal introitus was made, and a 9-cm canal was made between the bladder and the
      rectum using sharp and blunt dissection along the anatomic vaginal route, with
      the aid of laparoscopy to ensure correct orientation. A 14 * 12 cm split
      thickness skin graft was harvested from the right lateral thigh. By laparoscopy,
      the level of the lowest pole of the uterine cavity was exposed and the cervix was
      incised by shape dissection. The proximal segment of the harvested skin to the
      lower uterine segment was secured, and the distal segment was sutured with the
      upper margin of vulva vaginally. Surgical technique reports in anonymous patients
      are exempted from ethical approval by the Institutional Review Board. The patient
      gave consent to use the video in the article. RESULT(S): The procedure was
      successfully completed. Since February 2013, our experiences of combined
      laparoscopic and vaginal cervicovaginal reconstruction using split thickness skin
      graft in 10 patients with congenital atresia of cervix were positive, with
      successful results and without complications or cervical, or vaginal stenosis.
      CONCLUSION(S): Our technique is feasible and safe for congenital atresia of
      cervix, with successful results and without complications or cervical or vaginal
      stenosis.

PMID- 26211886
TI  - Improvements in lung function with umeclidinium/vilanterol versus fluticasone
      propionate/salmeterol in patients with moderate-to-severe COPD and infrequent
      exacerbations.

PMID- 26211887
TI  - Critical illness trajectory for patients, families and nurses - a literature
      review.
AB  - BACKGROUND: In the 21st century, we are starting to discover and understand the
      longer term sequelae of critical illness from both patient's and family members'
      perspectives. The consequential effects on physical and psychological function
      and the social landscape are being slowing realized. We are beginning to
      understand the long-term legacy of critical care, with survivorship possibly the
      greatest challenge within the critical care setting. AIM: To draw together
      research that has appraised the experience of surviving critical illness from the
      holistic, triadic perspectives of survivor, relative and critical care nurse. In
      doing so, knowledge of the complexities of the critical care trajectory is
      enhanced. SEARCH STRATEGY: Using Medline; Assia; CINAHL Plus; SCOPUS; Web of
      knowledge searches from 2000 to 2015 were conducted utilizing the terms 'critical
      care'; 'intensive care', ITU; patient*; relative*; family member*; experience*;
      nurse*, and trajectory. Relevant exclusion criteria were applied to provide a
      generalist adult critical care perspective. RESULTS: Following a process of
      constant comparative analysis of the literature and thematic synthesis, seven
      themes were highlighted. Facing mortality, critical junctures, physiological
      sequelae, psychological sequelae, family presence, beyond meeting the needs of
      family members and technology versus humanity were all emergent themes.
      CONCLUSION: As humans, we do not live an isolated life; we are interdependent
      upon each other. This inclusive review of literature has highlighted the lacunae
      and areas of dissonance both in the literature and in clinical practice in
      relation to the critical care trajectory as experienced by survivors of critical
      illness and their families. RELEVANCE TO CLINICAL PRACTICE: Critical care nurses
      can and should play a role in preparing and supporting patients and families
      beyond the critical care unit. In turn, Registered Nurses needed to be supported
      to fulfil this important role in enabling the process of moving patients and
      their families from surviving to thriving (survivorship).

PMID- 26211888
TI  - Intercalation complex of imidazoacridinone C-1311, a potential anticancer drug,
      with DNA helix d(CGATCG)2: stereostructural studies by 2D NMR spectroscopy.
AB  - Imidazoacridinone C-1311 (Symadex(r)) is a powerful antitumor agent, which
      successfully made its way through the Phase I clinical trials and has been
      recommended for Phase II few a years ago. It has been shown experimentally that
      during the initial stage of its action C-1311 forms a relatively stable
      intercalation complex with DNA, yet it has shown no base-sequence specificity
      while binding to DNA. In this paper, the d(CGATCG)2:C-1311 intercalation complex
      has been studied by means of two-dimensional NMR spectroscopy, yielding a full
      assignment of the resonance lines observed in (1)H NMR spectra. The observation
      of the intermolecular NOE contacts between C-1311 and DNA allowed locating the
      ligand between the guanine and adenine moieties. Formation of a symmetric complex
      was pointed out on the basis of the lack of a second set of the (1)H resonances.
      The resulting stereostructure of the complex was then improved by means of
      molecular dynamics, using the CHARMM force field and GROMACS software. To this
      end, distance restraints derived from the NOESY cross-peak volumes were applied
      to the atomistic model of the d(CGATCG)2:C-1311 complex. Obtained results are in
      full agreement with biochemical data on the mechanism of action of C-1311, in
      particular with the previously postulated post-intercalation enzymatic activation
      of the studied drug. 

PMID- 26211889
TI  - Amphipathic alpha-helices and putative cholesterol binding domains of the
      influenza virus matrix M1 protein are crucial for virion structure organisation.
AB  - The influenza virus matrix M1 protein is an amphitropic membrane-associated
      protein, forming the matrix layer immediately beneath the virus raft membrane,
      thereby ensuring the proper structure of the influenza virion. The objective of
      this study was to elucidate M1 fine structural characteristics, which determine
      amphitropic properties and raft membrane activities of the protein, via 3D in
      silico modelling with subsequent mutational analysis. Computer simulations
      suggest the amphipathic nature of the M1 alpha-helices and the existence of
      putative cholesterol binding (CRAC) motifs on six amphipathic alpha-helices. Our
      finding explains for the first time many features of this protein, particularly
      the amphitropic properties and raft/cholesterol binding potential. To verify
      these results, we generated mutants of the A/WSN/33 strain via reverse genetics.
      The M1 mutations included F32Y in the CRAC of alpha-helix 2, W45Y and W45F in the
      CRAC of alpha-helix 3, Y100S in the CRAC of alpha-helix 6, M128A and M128S in the
      CRAC of alpha-helix 8 and a double L103I/L130I mutation in both a putative
      cholesterol consensus motif and the nuclear localisation signal. All mutations
      resulted in viruses with unusual filamentous morphology. Previous experimental
      data regarding the morphology of M1-gene mutant influenza viruses can now be
      explained in structural terms and are consistent with the pivotal role of the
      CRAC-domains and amphipathic alpha-helices in M1-lipid interactions. 

PMID- 26211890
TI  - Conserved molecular switch interactions in modeled cardioactive RF-NH2 peptide
      receptors: Ligand binding and activation.
AB  - Peptides may act through G protein-coupled receptors to influence cardiovascular
      performance; thus, delineating mechanisms involved in signaling is a molecular
      based strategy to influence health. Molecular switches, often represented by
      conserved motifs, maintain a receptor in an inactive state. However, once the
      switch is broken, the transmembrane regions move and activation occurs. The
      molecular switches of Drosophila melanogaster myosuppressin (MS) receptors were
      previously identified to include a unique ionic lock and novel 3-6 lock, as well
      as transmission and tyrosine toggle switches. In addition to MS, cardioactive
      ligands structurally related by a C-terminal RF-NH2 include sulfakinin,
      neuropeptide F (NPF), short NPF, and FMRF-NH2-containing peptide subfamilies. We
      hypothesized receptor molecular switch motifs were conserved within a RF-NH2
      subfamily and across species. Thus, we investigated RF-NH2 receptor (RFa-R)
      molecular switches in D. melanogaster, Tribolium castaneum, Anopheles gambiae,
      Rhodnius prolixus, and Bombyx mori. Adipokinetic hormone (AKH), which does not
      contain a RF-NH2, was also examined. The tyrosine toggle switch and ionic lock
      showed a higher degree of conservation within a RF-NH2 subfamily than the
      transmission switch and 3-7 lock. AKH receptor motifs were not representative of
      a RF-NH2 subfamily. The motifs and interactions of switches in the RFa-Rs were
      consistent with receptor activation and ligand-specific binding. 

PMID- 26211891
TI  - Anti-tumoral activity of human salivary peptides.
AB  - Chemotherapy continues to be the standard treatment for advanced or metastasized
      cancer. However, commonly used chemotherapeutic agents may induce damage in
      healthy cells and tissues. Thus, in recent years, there has been an increased
      focus on the development of new, efficient anticancer drugs exhibiting low
      toxicity and that are not affected by mechanisms of chemoresistance. In the
      present work, we tested synthetic and naturally obtained human salivary peptides
      against breast, prostate, colon, osteosarcoma and bladder cancer cell lines (T47
      D, PC-3, HT-29, MG63, T-24, respectively). Results have showed that there is a
      reduced cell population increase that is peptide-, cell- and possibly pathway
      specific, with the most potent effect observed in observed in T-47D breast cancer
      cells. Protein expression and microscopy results further indicate that, in this
      cell line, the peptide with the sequence GPPPQGGRPQG (GG peptide) interferes with
      the ability of cell adhesion proteins to stabilize adherens junctions, such as E
      cadherin, leading to apoptosis. These promising results encourage future works
      aimed at disclosing the vast potential of salivary peptides as new therapeutic
      agents. 

PMID- 26211892
TI  - Oxytocin differentially effects 3beta-hydroxysteroid dehydrogenase and 5alpha
      reductase activities in prostate cancer cell lines.
AB  - It is known that oxytocin stimulates steroidogenesis in several organs by
      modulating activity of 3beta-hydroxysteroid dehydrogenases (HSD3B) and steroid
      5alpha-reductases (SRD5A). However, this has not been established in prostate
      cancer where these enzymes, key to local production of androgens, are increased.
      Analysis of both HSD3B and SRD5A activities using a live cell in situ
      colourimetric assay demonstrated that in PC-3 cells HSD3B activity was
      significantly increased by oxytocin whilst SRD5A activity was unchanged. This was
      confirmed in ELISA based assays of conversion of pregnenolone to progesterone and
      testosterone to dihydrotestosterone in cell lysates following treatment. In
      contrast, oxytocin significantly inhibited HSD3B activity in LNCaPs, but
      significantly increased activity of SRD5A, as confirmed by ELISA assays. Analysis
      of both cell lines by microarray and qRT-PCR determined that these changes were
      not due to altered gene transcription. This study demonstrates differential
      effects of oxytocin on the activities of key de novo steroidogenic enzymes in
      prostate cancer cells. 

PMID- 26211893
TI  - Spexin peptide is expressed in human endocrine and epithelial tissues and reduced
      after glucose load in type 2 diabetes.
AB  - Spexin mRNA and protein are widely expressed in rat tissues and associate with
      weight loss in rodents of diet-induced obesity. Its location in endocrine and
      epithelial cells has also been suggested. Spexin is a novel peptide that involves
      weight loss in rodents of diet-induced obesity. Therefore, we aimed to examine
      its expression in human tissues and test whether spexin could have a role in
      glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). The expression
      of the spexin gene and immunoreactivity in the adrenal gland, skin, stomach,
      small intestine, liver, thyroid, pancreatic islets, visceral fat, lung, colon,
      and kidney was higher than that in the muscle and connective tissue.
      Immunoreactive serum spexin levels were reduced in T2DM patients and correlated
      with fasting blood glucose (FBG, r=-0.686, P<0.001), hemoglobin A1c (HbA1c, r=
      0.632, P<0.001), triglyceride (TG, r=-0.236, P<0.001) and low density lipoprotein
      cholesterol (LDL-C, r=-0.382, P<0.001). A negative correlation of blood glucose
      with spexin was observed during oral glucose tolerance test (OGTT). Spexin is
      intensely expressed in normal human endocrine and epithelial tissues, indicating
      that spexin may be involved in physiological functions of endocrine and in
      several other tissues. Circulating spexin levels are low in T2DM patients and
      negatively related to blood glucose and lipids suggesting that the peptide may
      play a role in glucose and lipid metabolism in T2DM. 

PMID- 26211894
TI  - Effects of systematic N-terminus deletions and benzoylations of endogenous RF
      amide peptides on NPFF1R, NPFF2R, GPR10, GPR54 and GPR103.
AB  - Mammalian RF-amide peptides including RF-amide-related peptides-1 and -3,
      neuropeptides AF and FF, Prolactin releasing peptides, Kisspeptins and RFa
      peptides are currently considered endogenous peptides for the GPCRs NPFF1R,
      NPFF2R, GPR10, GPR54 and GPR103, respectively. While NPFF1R and NPFF2R displayed
      high affinity for all the RF-amide peptides, GPR10, GPR54 and GPR103 only bind
      their cognate ligands. Through a systematic and sequential N-terminus deletion
      and benzoylation of either RF-amide neuropeptide (RFRP-3, NPFF, Kp-10, PrRP20,
      and 26RFa), we report the corresponding impact on affinity and activity towards
      all the RF-amide receptors (NPFF1R, NPFF2R, GPR10, GPR54 and GPR103). Our results
      highlight the difficulty to develop selective peptide ligands for GPR10, GPR54 or
      GPR103 without a modification of the C-terminus RF-amide signature, but open the
      door to the design of new RF-amide peptides acting as agonist for one receptor
      and antagonist for another one. 

PMID- 26211896
TI  - Characteristic dermoscopic features of verruciform xanthoma: Report of three
      cases.

PMID- 26211895
TI  - Cortical Activation Patterns of Bodily Attention triggered by Acupuncture
      Stimulation.
AB  - We investigated commonalities and differences in brain responses to enhanced
      bodily attention around acupuncture points with and without stimulation. Fourteen
      participants received acupuncture needles at both PC6 and HT7 acupoints in the
      left hand. To enhance bodily attention to acupoints, participants responded to
      the locations of stimulations in a two-alternative forced choice task. Two fMRI
      scans were taken in a block design: session 1 labeled with manual stimulation
      (genuine stimulation) and session 2 labeled with electro-acupuncture (pseudo
      stimulation). To compare cortical activation patterns, data were analyzed using
      the Freesurfer software package. Both genuine-and pseudo-stimulation resulted in
      brain activations in the insula, anterior cingulate cortex, secondary
      somatosensory cortex, superior parietal cortex, and brain deactivation in the
      medial prefrontal cortex, posterior cingulate cortex, inferior parietal cortex,
      and the parahippocampus. Genuine acupuncture stimulation exhibited greater brain
      activation in the posterior insula, posterior operculum and the caudal part of
      the anterior cingulate cortex, compared with pseudo-stimulation. We demonstrated
      that enhanced bodily attention triggered by genuine acupuncture stimulation can
      activate the salience network and deactivate the default mode network regardless
      of the type of stimulation. The component of enhanced attention to a certain part
      of the body is significant in the brain response to acupuncture stimulation. 

PMID- 26211897
TI  - Intersex in fishes and amphibians: population implications, prevalence,
      mechanisms and molecular biomarkers.
AB  - Intersex is defined as the abnormal presence of both testicular and ovarian cells
      in gonads of gonochoristic animals. Its occurrence is widespread and reports on
      its presence in the gonads of vertebrates continues to increase. In this review,
      we use standardized terminology to summarize the current knowledge of intersex in
      gonochoristic fishes and amphibians. We describe the different indices that have
      been used to assess the severity of intersex and synthesize reports discussing
      the prevalence of intersex in relation to different types of pollutants. In
      addition, we evaluate the geographic distribution and chronology of the reported
      cases of intersex in fishes and amphibians, their pathological descriptions and
      severity and discuss species sensitivities. We also summarize molecular
      biomarkers that have been tested for early detection of intersex in wild
      populations and highlight additional biomarkers that target molecular pathways
      involved in gonadal development that require further investigation for use in the
      diagnosis of intersex. Finally, we discuss the needs for future research in this
      field.

PMID- 26211898
TI  - The prediction of total skeletal muscle mass in a Caucasian population -
      comparison of Magnetic resonance imaging (MRI) and Dual-energy X-ray
      absorptiometry (DXA).
AB  - Dual-energy X-ray (DXA) is an alternative to magnetic resonance imaging (MRI) to
      measure skeletal muscle mass. DXA assesses lean body mass (LBM), and MRI measures
      skeletal muscle mass (SMM). Kim et al. (Am J Clin Nutr 2002; 76: 378; J Appl
      Physiol (1985) 2004; 97: 655) developed MRI-based algorithms to estimate whole
      body SMM by DXA. These algorithms were based on an ethnically mixed study
      population (Kim et al., Am J Clin Nutr 2002; 76: 378; J Appl Physiol (1985) 2004;
      97: 655). It is unclear whether Kim's algorithms are accurate in an exclusive
      Caucasian population. The aim of our study was to validate Kim's equation in a
      Caucasian population of 346 subjects. SMMMRI was assessed using MRI, and LBM and
      BMCDXA were measured by DXA and fat mass (FMADP ) by air-displacement
      plethysmographie (ADP). SMMMRI and predicted SMM were highly correlated (r =
      0.944; P<0.05). The standard error of estimate of the regression equation was 2.4
      kg. However, Bland-Altman plots showed a significant (P<0.001) systematic bias
      between SMMMRI (median 25.1 kg; IQ 20.2-31.1 kg) and predicted SMM (median 26.3
      kg; IQ 22.6-33.0 kg), overestimating SMM by 9.8%. Multiple regression analyses
      showed that weight explained 4.4% of the variance in the differences between
      SMMMRI and predicted SMM with the major part unexplained. Kim's algorithm has a
      systematic unexplained bias and is not recommended in Caucasians.

PMID- 26211899
TI  - Exposure to ambient air pollution--does it affect semen quality and the level of
      reproductive hormones?
AB  - BACKGROUND: Ambient air pollution has been associated with a variety of
      reproductive disorders. However, a limited amount of research has been conducted
      to examine the association between air pollution and male reproductive outcomes,
      specifically semen quality. AIM: The present study was designed to address the
      hypothesis that exposure to fluctuating levels of specific air pollutants
      adversely affects sperm parameters and the level of reproductive hormones.
      SUBJECTS AND METHODS: The study population consisted of 327 men who were
      attending an infertility clinic in Lodz, Poland for diagnostic purposes and who
      had normal semen concentration of 15-300 mln/ml. All participants were
      interviewed and provided a semen sample. Air quality data were obtained from
      AirBase database. RESULTS: The statistically significant association was observed
      between abnormalities in sperm morphology and exposure to all examined air
      pollutants (PM10, PM2.5, SO2, NOX, CO). Exposure to air pollutants (PM10, PM2.5,
      CO, NOx) was also negatively associated with the level of testosterone.
      Additional exposure to PM2.5, PM10 increase the percentage of cells with immature
      chromatin (HDS). CONCLUSIONS: The present study provides suggestive evidence of
      an association between ambient air pollution and sperm quality. Further research
      is needed to explore this association in more detail. Individual precise exposure
      assessment would be needed for more detailed risk characterization.

PMID- 26211900
TI  - Positively charged self-nanoemulsifying oily formulations of olmesartan
      medoxomil: Systematic development, in vitro, ex vivo and in vivo evaluation.
AB  - The current research work explores the potential applications of cationic self
      nanoemulsifying oily formulations (CSNEOFs) for enhancing the oral
      bioavailability of olmesartan medoxomil. Initial preformulation studies, risk
      assessment and factor screening studies revealed selection of oleic acid, Tween
      40 and Transcutol HP as the critical factors. Systematic optimization of SNEOFs
      was carried out employing D-optimal mixture design and evaluating them for
      responses viz. emulsification efficiency, globule size and in vitro drug release.
      The CSNEOFs were prepared from the optimized SNEOFs by adding oleylamine as
      cationic charge inducer. In vitro cell line studies revealed markedly better drug
      uptake along with safer and biocompatible nature of CSNEOFs than free drug
      suspension. In situ perfusion, and in vivo pharmacokinetic and pharmacodynamic
      studies in Wistar rats revealed significant improvement in the biopharmaceutical
      performance of the drug from CSNEOFs and SNEOFs vis-a-vis the marketed
      formulation. Successful establishment of various levels of in vitro/in vivo
      correlations (IVIVC) substantiated high degree of prognostic ability of in vitro
      dissolution conditions in predicting the in vivo performance. In a nutshell, the
      present studies report successful development of CSNEOFs of olmesartan medoxomil
      with distinctly improved biopharmaceutical performance. 

PMID- 26211901
TI  - Calculation of injection forces for highly concentrated protein solutions.
AB  - Protein solutions often manifest a high viscosity at high solution
      concentrations, thus impairing injectability. Accordingly, accurate prediction of
      the injection force based on solution viscosity can greatly support protein
      formulation and device development. In this study, the shear-dependent viscosity
      of three concentrated protein solutions is reported, and calculated injection
      forces obtained by two different mathematical models are compared against
      measured values. The results show that accurate determination of the needle
      dimensions and the shear-thinning behavior of the protein solutions is vital for
      injection force prediction. Additionally, one model delivered more accurate
      results, particularly for solutions with prominent shear-thinning behavior. 

PMID- 26211902
TI  - Lipid nanocarriers containing sorafenib inhibit colonies formation in human
      hepatocarcinoma cells.
AB  - Here, the potential of two nanostructured lipid carriers (NLC) for controlled
      release of sorafenib was evaluated. The obtained systems showed characteristics
      suitable as drug delivery systems for the treatment of hepatocellular carcinoma
      (HCC) through parenteral administration. The use of a mixture between a solid
      lipid (tripalmitin) with a liquid lipid (Captex 355 EP/NF or Miglyol 812) to
      prepare NLC systems could give a higher drug loading capacity and a longer term
      stability during storage than that obtained by using only solid lipids. The
      obtained nanoparticles showed a nanometer size and high negative zeta potential
      values. Scansion electron microscopy (SEM) of the sorafenib loaded NLC revealed a
      spherical shape with a diameter <300 nm. In vitro biological studies demonstrated
      that sorafenib loaded into NLC had enhanced anti-tumor activity compared to that
      of free drug. This finding raises hope in terms of future drug delivery strategy
      of sorafenib loaded NLC, that can be useful for therapeutic application in HCC.

PMID- 26211903
TI  - Formulation and evaluation of cefuroxim loaded submicron particles for ophthalmic
      delivery.
AB  - Chitosan gelatin particles could be the ideal candidate for intraocular drug
      delivery due to their desirable properties. Double crosslinking in double
      emulsion has been used as an original and reliable method for particles
      preparation and their morphology has been optimized considering the main
      synthesis parameters such as polymers ratio, crosslinker amount, stirring speed,
      tensioactive amount and ionic crosslinking time, respectively. The particles have
      been analyzed for their physical-chemical properties (swelling degree, drug
      loading and release capacity, surface characteristics, etc.), the enzymatic
      degradation properties along with in vivo ocular investigations (ocular
      biodistribution, in vivo drug release). In the present study cefuroxim was used
      as a model drug, which is generally used in the prophylaxis of postoperative
      endophthalmitis following cataract surgery after intraocular administration. The
      present study proved that the dimensions and the physical-chemical properties of
      the particles can be modulated (by varying the preparation parameters) to
      facilitate the administration, the biodistribution and the drug release in the
      specific segment of the eye. This experimental study demonstrated also the
      ability of fluorescent nanoparticles to penetrate ocular tissues close to the
      administration site (intravitreal injection) and especially their tendency to
      migrate deep in the retina at time intervals of 72 h.

PMID- 26211904
TI  - A Hybrid Supramolecular Polymeric Hydrogel with Rapid Self-Healing Property.
AB  - A hybrid supramolecular polymeric hydrogel is conveniently constructed via host
      guest interaction of a host cyclodextrin polymer (poly-CD) with a guest alpha
      bromonaphthalene polymer (poly-BrNp) and mixing with 6-thio-beta-cyclodextrin
      (beta-SH-CD) modified gold nanoparticles (GPCDs) in aqueous solution. According
      to the dynamic oscillatory data, the hydrogel exhibits markedly enhanced
      stiffness compared with the GPCD-free one (both G' and G" values are almost twice
      as high as those of the original GPCD-free hydrogel) due to the introduction of
      the inorganic gold nanoparticles. This hybrid supramolecular polymeric hydrogel
      has a rapid and excellent self-healing property (only about 1 min, and the G' and
      G" of the self-healed hydrogel almost turned back to their original levels after
      1 hour) in air (without adding any solvent or additive). 

PMID- 26211906
TI  - A 6,11,16-Triarylbiphenylcorrole with an adj-CCNN Core: Stabilization of an
      Organocopper(III) Complex.
AB  - An adj-dicarbacorrole with CCNN in the core is achieved by replacing the
      bipyrrole moiety by a simple polycyclic aromatic hydrocarbon, such as biphenyl
      unit. Spectroscopic studies and structural analyzes confirm the absence of
      macrocyclic aromatization, thus leading to overall nonaromatic character. The
      trianionic core is effectively utilized to stabilize a copper(III) ion to form an
      organocopper complex. 

PMID- 26211905
TI  - Hematopoietic pre-B cell leukemia transcription factor interacting protein is
      overexpressed in gastric cancer and promotes gastric cancer cell proliferation,
      migration, and invasion.
AB  - Hematopoietic pre-B cell leukemia transcription factor interacting protein (HPIP)
      has been shown to play an important role in the development and progression of
      some cancers. However, the role of HPIP in gastric cancer (GC) is unclear. Here,
      we show that HPIP is upregulated in most GC patients and promotes GC cell
      proliferation, migration, and invasion. In GC patients, HPIP positively
      associates with tumor size and nodal metastasis, and negatively associates with
      tumor differentiation. Hematopoietic pre-B cell leukemia transcription factor
      interacting protein increases GC cell proliferation through activation of G1 /S
      and G2 /M cell cycle transitions, accompanied by a marked increase of the
      positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1.
      Hematopoietic pre-B cell leukemia transcription factor interacting protein
      enhances GC cell migration and invasion, and modulates epithelial-mesenchymal
      transition, which plays a key role in cancer cell migration and invasion. These
      data underscore the critical role of HPIP in GC cell proliferation and
      progression and suggest that HPIP inhibition may be a useful therapeutic strategy
      for GC treatment. 

PMID- 26211907
TI  - Cooperative Gold Nanoparticle Stabilization by Acetylenic Phosphaalkenes.
AB  - Acetylenic phosphaalkenes (APAs) are used as a novel type of ligands for the
      stabilization of gold nanoparticles (AuNP). As demonstrated by a variety of
      experimental and analytical methods, both structural features of the APA, that
      is, the P=C as well as the C=C units are essential for NP stabilization. The
      presence of intact APAs on the AuNP is demonstrated by surface-enhanced Raman
      spectroscopy (SERS), and first principle calculations indicate that bonding
      occurs most likely at defect sites on the Au surface. AuNP-bound APAs are in
      chemical equilibrium with free APAs in solution, leading to a dynamic behavior
      that can be explored for facile place-exchange reactions with other types of
      anchor groups such as thiols or more weakly binding phosphine ligands.

PMID- 26211908
TI  - Effect of test concentration in the ready biodegradability test for chemical
      substances: Improvement of OECD test guideline 301C.
AB  - In Japan, understanding the environmental persistence of chemicals is very
      important for risk assessment, and ready biodegradability tests are mainly
      conducted according to the Organisation for Economic Co-operation and Development
      test guideline 301C. However, the highest test concentration specified in test
      guideline 301C, 100 mg/L, may cause microbial toxicity and incomplete
      biodegradation. The authors performed test guideline 301C tests at test
      concentrations of 30 mg/L for 13 substances that were readily biodegradable in
      ready biodegradability tests but not in test guideline 301C tests. Of the 5
      substances with potential to cause microbial toxicity at 100 mg/L, the percentage
      of biodegradation of sodium dimethyldithiocarbamate, 4-chloro-3-cresol (CC),
      thymol (THY), and p-tert-butyl-alpha-methylbenzenepropionaldehyde measured by
      biochemical oxygen demand (BOD) increased in the test guideline 301C test at 30
      mg/L, suggesting a reduction in toxicity effects. Furthermore, CC and THY met the
      criteria for ready biodegradability, which are more than 60% of biodegradation by
      BOD and a 10-d window. Of the 8 substances with a low potential for causing
      microbial toxicity at 100 mg/L, the percentage of biodegradation of only 2
      (diethylamino)ethanol increased in the test guideline 301C test at 30 mg/L.
      Employing a lower test concentration in the standard test guideline 301C test
      will contribute to improvement of consistency between results of a test guideline
      301C test and other ready biodegradability tests.

PMID- 26211909
TI  - Clinical Cell Cycle Analysis Revisited.

PMID- 26211915
TI  - Human platelet antigen genotyping of platelet donors in southern Brazil.
AB  - Human platelet antigens (HPA) are immunogenic structures that result from single
      nucleotide polymorphisms (SNPs) leading to single amino acid substitutions. This
      study sought to determine the allele and genotype frequencies of HPA-1, HPA-2,
      HPA-3, HPA-4, HPA-5 and HPA-15 in platelet donors from the state of Rio Grande do
      Sul (RS), Brazil, and compare their allele frequencies to those observed in other
      populations. HPA genotyping was performed by PCR-SSP method. The study sample
      comprised 201 platelet donors (167 Caucasians and 34 non-Caucasians). Allele 'a'
      was that most commonly found for HPA-1 to 5 in both groups. The HPA-15ab genotype
      predominated over homozygous genotypes of this system. Fisher's exact test
      revealed statistically significant differences for the HPA-5 system, with a
      greater prevalence of the HPA-5b allele in non-Caucasians. The neighbour-joining
      method and principal components analysis revealed genetic proximity between our
      Caucasian group and European populations. We conclude that the allele frequencies
      of HPA-1 to 5 and HPA-15 found in our Caucasian sample are similar to those
      reported for European populations. These findings corroborate the ethnic makeup
      of the population of RS. The higher frequency of the HPA-5b allele found in the
      non-Caucasian group of our sample suggests the possibility of allosensitization
      in patients who receive platelet transfusions from genetically incompatible
      donors. 

PMID- 26211916
TI  - Molecular dynamics simulations indicate that tyrosineB10 limits motions of distal
      histidine to regulate CO binding in soybean leghemoglobin.
AB  - Myoglobin (Mb) uses strong electrostatic interaction in its distal heme pocket to
      regulate ligand binding. The mechanism of regulation of ligand binding in soybean
      leghemoglobin a (Lba) has been enigmatic and more so due to the absence of
      gaseous ligand bound atomic resolution three-dimensional structure of the plant
      globin. While the 20-fold higher oxygen affinity of Lba compared with Mb is
      required for its dual physiological function, the mechanism by which this high
      affinity is achieved is only emerging. Extensive mutational analysis combined
      with kinetic and CO-FT-IR spectroscopic investigation led to the hypothesis that
      Lba depended on weakened electrostatic interaction between distal HisE7 and bound
      ligand achieved by invoking B10Tyr, which itself hydrogen bonds with HisE7 thus
      restricting it in a single conformation detrimental to Mb-like strong
      electrostatic interaction. Such theory has been re-assessed here using CO-Lba in
      silico model and molecular dynamics simulation. The investigation supports the
      presence of at least two major conformations of HisE7 in Lba brought about by
      imidazole ring flip, one of which makes hydrogen bonds effectively with B10Tyr
      affecting the former's ability to stabilize bound ligand, while the other does
      not. However, HisE7 in Lba has limited conformational freedom unlike high
      frequency of imidazole ring flips observed in Mb and in TyrB10Leu mutant of Lba.
      Thus, it appears that TyrB10 limits the conformational freedom of distal His in
      Lba, tuning down ligand dissociation rate constant by reducing the strength of
      hydrogen bonding to bound ligand, which the freedom of distal His of Mb allows.

PMID- 26211917
TI  - Iridium(III) Photocatalysis: A Visible-Light-Induced Dearomatizative Tandem [4+2]
      Cyclization to Furnish Benzindolizidines.
AB  - A photocatalytic dearomatizative tandem [4+2] cyclization between N-(2
      iodoethyl)indoles and a variety of alkenes leads to tri- and tetracyclic
      benzindolizidines with high diastereoselectivity and yield. The intermolecular
      annulation reaction is performed under visible-light irradiation and employs
      [Ir(ppy)3] or [Ir(dtbbpy)(ppy)2] PF6 as photocatalysts, in combination with
      tertiary amines as electron and hydrogen atom donors.

PMID- 26211918
TI  - High prevalence of hepatitis E virus antibodies among blood donors in Southern
      Brazil.
AB  - Brazil has been classified as moderately endemic for hepatitis E virus (HEV)
      infection. However, data on the seroprevalence of HEV in this region are limited.
      This study evaluated the prevalence of past or present HEV infection among blood
      donors in the metropolitan area of Itajai Valley, Southern Brazil, a region of
      predominant German heritage, where cultural habits result in a high consumption
      of pork. Serum samples from 300 blood donors were tested in December 2014 using
      serological and molecular methods. Anti-HEV IgG antibodies were detected in 30
      (10%) subjects, and categorized age groups revealed an age-dependent increase of
      HEV seroprevalence. Only one subject had anti-HEV IgM, whereas none tested
      positive for HEV-RNA. The present data demonstrate a higher seroprevalence of
      anti-HEV IgG in blood donors than previously reported in Brazil.

PMID- 26211919
TI  - Anemia among Muslim Bedouin and Jewish women of childbearing age in Southern
      Israel.
AB  - There are inequalities in health indicators among different ethnic groups living
      in the same region and receiving the same medical services. Anemia is a global
      problem. Although the prevalence of anemia is not high in Israel, differences
      among ethnic groups have not been studied. Our objective was to assess anemia
      among Bedouin and Jewish women of childbearing age in southern Israel. A
      retrospective observational study was conducted based on data from computerized
      medical records. Seven thousand eight hundred seventy-one women in the study
      clinics underwent complete blood counts and had blood hemoglobin levels of 11
      g/dl or below. The Jewish patients were older (31.7 vs. 29.7 years, P < 0.001),
      practiced birth control more (24.2 vs. 9.9 %, P < 0.001), and adhered to it more
      (81.1 vs. 61.9 %, P < 0.001). Bedouin women had more children (3.7 vs. 1.9, P <
      0.001), and more Bedouin women were pregnant during the study period (49.3 vs.
      35.0 %, P < 0.001). The most prevalent types of anemia were iron deficiency and
      anemia of chronic disease. Two types of anemia were proportionally higher among
      Jewish women, anemia of chronic disease (18.1 vs. 9.7 %, P < 0.001) and folic
      acid deficiency (3.3 vs. 2.2 %, P > 0.001). The adherence rates for treatment
      were very low. Three factors associated with severe anemia (hemoglobin below 8
      g/dl) were being Bedouin (odds ratio (OR) = 1.295, P < 0.001), use of birth
      control (OR = 0.419, P < 0.001), and pregnancy (OR = 0.447, P < 0.001). Being a
      Bedouin woman is a risk factor for severe anemia, and adherence to treatment for
      anemia is very low in both groups. These findings should be addressed in a
      national program to reduce health inequalities. 

PMID- 26211920
TI  - A systematic review and individual patient data meta-analysis of prognostic
      factors for foot ulceration in people with diabetes: the international research
      collaboration for the prediction of diabetic foot ulcerations (PODUS).
AB  - BACKGROUND: Annual foot risk assessment of people with diabetes is recommended in
      national and international clinical guidelines. At present, these are consensus
      based and use only a proportion of the available evidence. OBJECTIVES: We
      undertook a systematic review of individual patient data (IPD) to identify the
      most highly prognostic factors for foot ulceration (i.e. symptoms, signs,
      diagnostic tests) in people with diabetes. DATA SOURCES: Studies were identified
      from searches of MEDLINE and EMBASE. REVIEW METHODS: The electronic search
      strategies for MEDLINE and EMBASE databases created during an aggregate
      systematic review of predictive factors for foot ulceration in diabetes were
      updated and rerun to January 2013. One reviewer applied the IPD review
      eligibility criteria to the full-text articles of the studies identified in our
      literature search and also to all studies excluded from our aggregate systematic
      review to ensure that we did not miss eligible IPD. A second reviewer applied the
      eligibility criteria to a 10% random sample of the abstract search yield to check
      that no relevant material was missed. This review includes exposure variables
      (risk factors) only from individuals who were free of foot ulceration at the time
      of study entry and who had a diagnosis of diabetes mellitus (either type 1 or
      type 2). The outcome variable was incident ulceration. RESULTS: Our search
      identified 16 cohort studies and we obtained anonymised IPD for 10. These data
      were collected from more than 16,000 people with diabetes worldwide and
      reanalysed by us. One data set was kept for independent validation. The data sets
      contributing IPD covered a range of temporal, geographical and clinical settings.
      We therefore selected random-effects meta-analysis, which assumes not that all
      the estimates from each study are estimates of the same underlying true value,
      but rather that the estimates belong to the same distribution. We selected
      candidate variables for meta-analysis using specific criteria. After univariate
      meta-analyses, the most clinically important predictors were identified by an
      international steering committee for inclusion in the primary, multivariable meta
      analysis. Age, sex, duration of diabetes, monofilaments and pulses were
      considered most prognostically important. Meta-analyses based on data from the
      entire IPD population found that an inability to feel a 10-g monofilament [odds
      ratio (OR) 3.184, 95% confidence interval (CI) 2.654 to 3.82], at least one
      absent pedal pulse (OR 1.968, 95% CI 1.624 to 2.386), a longer duration of a
      diagnosis of diabetes (OR 1.024, 95% CI 1.011 to 1.036) and a previous history of
      ulceration (OR 6.589, 95% CI 2.488 to 17.45) were all predictive of risk. Female
      sex was protective (OR 0.743, 95% CI 0.598 to 0.922). LIMITATIONS: It was not
      possible to perform a meta-analysis using a one-step approach because we were
      unable to procure copies of one of the data sets and instead accessed data via
      Safe Haven. CONCLUSIONS: The findings from this review identify risk assessment
      procedures that can reliably inform national and international diabetes clinical
      guideline foot risk assessment procedures. The evidence from a large sample of
      patients in worldwide settings show that the use of a 10-g monofilament or one
      absent pedal pulse will identify those at moderate or intermediate risk of foot
      ulceration, and a history of foot ulcers or lower-extremity amputation is
      sufficient to identify those at high risk. We propose the development of a
      clinical prediction rule (CPR) from our existing model using the following
      predictor variables: insensitivity to a 10-g monofilament, absent pedal pulses
      and a history of ulceration or lower-extremities amputations. This CPR could
      replace the many tests, signs and symptoms that patients currently have measured
      using equipment that is either costly or difficult to use. STUDY REGISTRATION:
      This study is registered as PROSPERO CRD42011001841. FUNDING: The National
      Institute for Health Research Health Technology Assessment programme.

PMID- 26211921
TI  - Investigation of a leptospirosis outbreak in triathlon participants, Reunion
      Island, 2013.
AB  - We report herein the investigation of a leptospirosis outbreak occurring in
      triathlon competitors on Reunion Island, Indian Ocean. All participants were
      contacted by phone or email and answered a questionnaire. Detection and molecular
      characterization of pathogenic Leptospira was conducted in inpatients and in
      rodents trapped at the vicinity of the event. Of the 160 athletes competing, 101
      (63.1%) agreed to participate in the study. Leptospirosis was biologically
      confirmed for 9/10 suspected cases either by real-time PCR or serological tests
      (MAT or ELISA). The total attack rate, children's attack rate, swimmers' attack
      rate, and the attack rate in adult swimmers were respectively estimated at 8.1%
      [95% confidence interval (CI) 4.3-14.7], 0%, 12.7% (95% CI 6.8-22.4) and 23.1%
      (95% CI 12.6-33.8). Leptospirosis cases reported significantly more wounds [risk
      ratio (RR) 4.5, 95% CI 1.6-13], wore complete neoprene suits less often (RR 4.3,
      95% CI 1.3-14.5) and were most frequently unlicensed (RR 6.6, 95% CI 2.9-14.8).
      The epidemiological investigation supported that some measures such as the use of
      neoprene suits proved efficient in protecting swimmers against infection. PCR
      detection in rats revealed high Leptospira infection rates. Partial sequencing of
      the 16S gene and serology on both human and animal samples strongly suggests that
      rats were the main contaminators and were likely at the origin of the infection
      in humans. 

PMID- 26211922
TI  - Effects of different five-day progesterone-based synchronization protocols on the
      estrous response and follicular/luteal dynamics in dairy cows.
AB  - This study compared the responses shown by lactating dairy cows to four different
      P4-based protocols for AI at estrus. Cows with no estrous signs 96 h after
      progesterone intravaginal device (PRID) removal were subjected to fixed-time AI
      (FTAI), and their data were also included in the study. In Experiment I,
      follicular/luteal and endometrial dynamics were assessed every 12 h from the
      beginning of treatment until AI. The estrous response was examined in Experiment
      II, and fertility was assessed in both experiments. The protocols consisted of a
      PRID fitted for five days, along with the administration of different
      combinations of gonadotropin releasing hormone (GnRH), equine chorionic
      gonadotropin and a single or double dose (24 h apart) of prostaglandin F2alpha.
      In Experiment I (40 cows), animals receiving GnRH at the start of treatment
      showed a significantly higher ovulation rate during the PRID insertion period
      while estrus was delayed. In Experiment II (351 cows), according to the odds
      ratios, cows showing luteal activity at the time of treatment were less likely to
      show estrus than cows with no signs of luteal activity. Treatment affected the
      estrous response and the interval from PRID removal to estrus but did not affect
      conception rates 28-34 days post AI. Primiparous cows displayed a better estrous
      response than multiparous cows. Our findings reveal acceptable results of 5-day
      P4-based protocols for AI at estrus in high-producing dairy cows. Time from
      treatment to estrus emerged as a good guide for FTAI after a 5-day P4-based
      synchronization protocol. 

PMID- 26211923
TI  - The challenge of the standardization of nursing specializations in Europe.
AB  - BACKGROUND: The evolution of health care is driving the need for specialist
      nursing knowledge. Specialist nurses have undertaken a formal training that
      focuses on a specific clinical area or population and are legitimated by a
      professional award or legal status. Specialist nurses are better able to provide
      the most specific and most appropriate care for both people and populations. AIM:
      This paper considers nursing's loose understanding of 'specialization' and the
      impact this has on those who seek employment outside their own nation but within
      the family of nations known as the European Union (EU). There is a lack of
      standardization for nursing specializations across the European Union that leads
      to lack of mobility across countries. SOURCES OF EVIDENCE: Reports were reviewed
      from within the European Union, including specialist nursing groups and
      regulatory nursing bodies. DISCUSSION: Nurse specialists can be regarded as
      operating at nursing's 'leading edge'; however, it is here that nursing lacks
      organization and common standards. This is readily apparent in a EU bound
      together by the principle of freedom of movement and common professional and
      academic standards. CONCLUSION: It is now time for European Union nurses to look
      beyond the common standards for pre-registration courses and to consider the
      development of common standards for specialist nursing. Historical attempts to
      achieve common standards for specialist nursing have largely been unsuccessful
      due to the diversity of approaches to nurse specialization. It is time now for
      this challenge to be re-addressed so that specialist nurses can more freely work
      throughout the European Union. IMPLICATIONS FOR NURSING POLICY: There is a
      pressing need for policy makers to define specialist nursing and to enable
      European Union-wide standards.

PMID- 26211924
TI  - Trypanosomatids in ornithophilic bloodsucking Diptera.
AB  - Trypanosomes are known as widespread blood parasites of birds; however, knowledge
      of their prevalences in vectors and their overall biodiversity is rather limited.
      To assess the prevalences in potential vectors, we have microscopically examined
      ornithophilic bloodsucking Diptera (Culicidae, Simuliidae and Hippoboscidae) for
      the presence of trypanosomatids in their guts. In total, 3270 specimens were
      dissected, namely Culex pipiens Linnaeus, 1758 (n = 898), C. modestus Ficalbi,
      1890 (136), Simulium vernum (Macquart, 1838) (1455), S. angustipes Edwards, 1915
      (221) and Ornithomyia avicularia (Linnaeus, 1758) (560). All insect species were
      found to be infected with trypanosomatids, and the prevalence ranged from 4 to 8%
      but reached 60% in S. vernum. Blackflies and hippoboscids exclusively harboured
      trypanosomes (both T. cf. avium s.s. Danilewsky, 1885; T. corvi/culicavium group
      in hippoboscids). Mosquitoes were infected with T. culicavium Votypka, 2012 and
      T. avium s. l. but also with monoxenous parasites, namely Crithidia brevicula
      Frolov and Malysheva, 1989, and Paratrypanosoma confusum Votypka and Lukes, 2013.
      Only 4% of the isolated parasite strains were monoxenous whereas the majority
      were avian trypanosomes, confirming the vectorial status of the studied insects. 

PMID- 26211925
TI  - Metabolic suppression during mesodermal differentiation of embryonic stem cells
      identified by single-cell comprehensive gene expression analysis.
AB  - Flk-1 (VEGF receptor 2) is a well-defined mesodermal progenitor marker and the
      Flk-1-positive (Flk-1(+)) cells derived from embryonic stem cells (ESCs) have
      been known to generate hemangioblasts and cardiovascular progenitor cells, which
      are formed in the early and late stages of differentiation, respectively. In this
      study, we separated Flk-1(+) and Flk-1(-) cells from spontaneously
      differentiating embryoid bodies (EBs) of mouse ESCs. We found that cell
      aggregates derived from late stage Flk-1(+) cells had a relatively small size and
      a low oxygen consumption rate (OCR) compared with those derived from Flk-1(-)
      cells. Furthermore, using single-cell comprehensive gene expression analysis, we
      found that both Flk-1(+) and Flk-1(-) cells could be categorized into subgroups
      with either low or high glucose metabolic activity. We observed that metabolic
      suppression occurs in cells expressing an intermediate level of both Nanog and
      Pou5f1. Taken together, our data suggested that the temporary metabolic
      suppression is an intrinsic feature of mesodermal differentiation. 

PMID- 26211926
TI  - Thermodynamic properties of neutral and charged oxygen vacancies in BaZrO3 based
      on first principles phonon calculations.
AB  - The structural, electronic and thermodynamic properties of neutral and positively
      doubly charged oxygen vacancies in BaZrO3 are addressed by first principles
      phonon calculations. The calculations are performed using two complementary first
      principles approaches and functionals; the linear combination of atomic orbitals
      (LCAO) within the hybrid Hartree-Fock and density functional theory formalism (HF
      DFT), and the projector augmented plane wave approach (PAW) within DFT. Phonons
      are shown to contribute significantly to the formation energy of the charged
      oxygen vacancy at high temperatures (~1 eV at 1000 K), due to both its large
      distortion of the local structure, and its large negative formation volume. For
      the neutral vacancy, the resulting lattice distortions, and thus the
      contributions from phonons to the free formation energy, are significantly
      smaller. As a result, phonons affect the relative stability of the two defects at
      finite temperatures and the charge transition level for oxygen vacancies (+2/0)
      changes from 0.42 to 0.83 eV below the conduction band bottom from 0 K to 1000 K.

PMID- 26211927
TI  - Primary Cytomegalovirus Infection Significantly Impacts Circulating T Cells in
      Kidney Transplant Recipients.
AB  - Cytomegalovirus (CMV) infection profoundly affects the T cell compartment and is
      associated with alterations in T cell aging parameters and generation of
      cytotoxic CD4(+) CD28null T cells. Hence, the effect of a primary CMV infection
      post-kidney transplantation (KT) on the peripheral T cell compartment was
      examined. As aging parameters, we determined the T cell differentiation status, T
      cell receptor excision circle (TREC) content, CD31(+) naive T cell numbers and
      relative telomere length (RTL) pre-KT and 12 months post-KT. CMV-seronegative KT
      recipients, receiving a kidney from a CMV-seropositive donor (D+/R-) were
      compared to D+/R+ KT recipients. Eleven out of the 22 D+/R- KT recipients had CMV
      viremia post-KT. They developed CMV-specific CD4(+) and CD8(+) T cells and their
      T cell compartment shifted towards a more differentiated memory phenotype with
      expansion of CD4(+) CD28null and CD8(+) CD28null cells. One year post-KT, the
      CD8(+) T cell count was almost doubled compared to nonviremic D+/R- and D+/R+ KT
      recipients. In addition, the RTL of the CD8(+) T cell was significantly lower and
      both the TREC content and CD31(+) naive T cell numbers significantly decreased.
      Moreover, primary CMV infection was associated with a negative impact on
      glomerular filtration rate. In conclusion, primary CMV infection has a
      substantial impact on the number and phenotype of peripheral T cells and may
      negatively affect renal allograft function. 

PMID- 26211928
TI  - Pleomorphic giant cell carcinoma of the urinary bladder: an extreme form of
      tumour de-differentiation.
AB  - AIMS: Vesical pleomorphic giant cell carcinoma (PGCC) is a variant of urothelial
      carcinoma (UC) characterized by highly pleomorphic tumour with giant cells. Fewer
      than 10 cases have been reported, and our aim was to determine the clinical and
      pathological features of a series of tumours from a specialized uropathology
      laboratory. METHODS AND RESULTS: Thirteen cases of PGCC of the bladder were
      identified. There were nine males and four females, ranging in age from 53 to 92
      years (mean 72 years). Associated conventional high-grade UC was seen in eight
      cases, while three cases also had micropapillary UC and one plasmacytoid UC. UC
      in situ (CIS) was present in five cases and occasional bizarre cells were seen in
      both UC and CIS. The proportion of PGCC present varied from 40% to 100% of
      tumour. Immunostaining performed on 10 cases showed uniform positivity for CK
      8/18 and AE1/AE3, while most tumours were positive for CK7, CK20, uroplakin III
      and GATA binding protein 3 (GATA3). beta-human chorionic gonadotrophin (beta-hCG)
      was negative. Of 10 patients with follow-up, five died within 1 year and four are
      alive with tumour. CONCLUSIONS: The association of PGCC with UC and an overlap in
      immunoexpression suggests that PGCC represents an extreme form of UC de
      differentiation.

PMID- 26211929
TI  - Simulating the influence of plasma protein on measured receptor affinity in
      biochemical assays reveals the utility of Schild analysis for estimating compound
      affinity for plasma proteins.
AB  - BACKGROUND AND PURPOSE: Plasma protein binding (PPB) influences the free fraction
      of drug available to bind to its target and is therefore an important
      consideration in drug discovery. While traditional methods for assessing PPB
      (e.g. rapid equilibrium dialysis) are suitable for comparing compounds with
      relatively weak PPB, they are not able to accurately discriminate between highly
      bound compounds (typically >99.5%). The aim of the present work was to use
      mathematical modelling to explore the potential utility of receptor binding and
      cellular functional assays to estimate the affinity of compounds for plasma
      proteins. Plasma proteins are routinely added to in vitro assays, so a secondary
      goal was to investigate the effect of plasma proteins on observed ligand-receptor
      interactions. EXPERIMENTAL APPROACH: Using the principle of conservation of mass
      and the law of mass action, a cubic equation was derived describing the ligand
      receptor complex [LR] in the presence of plasma protein at equilibrium. KEY
      RESULTS: The model demonstrates the profound influence of PPB on in vitro assays
      and identifies the utility of Schild analysis, which is usually applied to
      determine receptor-antagonist affinities, for calculating affinity at plasma
      proteins (termed KP ). We have also extended this analysis to functional effects
      using operational modelling and demonstrate that these approaches can also be
      applied to cell-based assay systems. CONCLUSIONS AND IMPLICATIONS: These
      mathematical models can potentially be used in conjunction with experimental data
      to estimate drug-plasma protein affinities in the earliest phases of drug
      discovery programmes.

PMID- 26211930
TI  - Iron Deficiency and IL1beta Polymorphisms in Helicobacter pylori-infected
      Children.
AB  - BACKGROUND: Helicobacter pylori infection has been associated with an imbalance
      of iron homeostasis. IL-1beta has been related with iron absorption disturbances
      through a variety of mechanisms. The aim of this study was to evaluate the
      presence of polymorphic variants for IL-1beta cluster and gastric IL1beta mRNA
      expression in H. pylori-infected children and their relationship with
      hypochlorhydria and iron deficiency (ID). PATIENTS AND METHODS: Prospective study
      of 123 symptomatic children. At endoscopy, antral biopsies were taken for urease
      test, pathology and culture and blood for analysis of ferritin, transferrin,
      serum iron, and total iron-binding capacity. Polymorphisms in the IL-1beta
      cluster (positions -511, -31, +3954, ILRN) were determined by PCR-RFLP. Gastric
      mucosal expression of IL-1beta mRNA was determined by RT-PCR. RESULTS: After
      exclusions, of 105 patients, 33 (31.4%) were H. pylori positive. Nine (8.6%)
      children were classified as iron deficient (ID). Helicobacter pylori positivity
      was associated with ID (OR: 5.1; 95% CI: 1.2-21.9) (p = .04). No significant
      differences were found in allele frequency for IL1beta gene cluster polymorphisms
      between infected and uninfected children. Helicobacter pylori-infected children
      with ID had significantly increased gastric IL1beta mRNA in comparison with
      infected children without ID. In addition, a significant positive correlation was
      observed between mucosal IL-1beta mRNA and fasting gastric juice pH. Gastric pH
      values were significantly increased in H. pylori-infected patients with ID
      compared to uninfected children. CONCLUSIONS: The established association between
      H. pylori infection and ID in children may be mediated by increased gastric
      mucosal IL-1beta.

PMID- 26211931
TI  - Mutations in EXPH5 underlie a rare subtype of autosomal recessive epidermolysis
      bullosa simplex.

PMID- 26211932
TI  - Primary Ewing Sarcoma Presenting as a Vulvar Mass in an Adolescent: Case Report
      and Review of Literature.
AB  - BACKGROUND: Extraosseous Ewing sarcoma (ES) tumors presenting in the
      genitourinary tract are highly uncommon. Few cases of primary vulvar and vaginal
      cases of ES have been published. CASE: A 15-year-old adolescent presented with a
      bothersome 5-cm mass located on her left labium minorum. Following excision, a
      diagnosis of a primary ES was made. The patient was treated with multiagent
      chemotherapy and was doing well 20 months after treatment completion. SUMMARY AND
      CONCLUSION: Based on the few available case reports and our reported case, it
      appears that extraosseous ES arising in superficial sites such as the vulva have
      better prognosis and should be treated with complete excision and multiagent
      chemotherapy.

PMID- 26211934
TI  - Gender differences in the association between cohabitation with parents and
      stress among married adults: A propensity score-matched analysis from the Korean
      National Health and Nutrition Examination Survey (KNHANES).
AB  - This study examined the gender-specific associations between cohabitation with
      parents and stress using an econometric approach. A total of 13,565 (41.7% men
      and 58.3% women) Korean adults aged 20-59 years from the Korean National Health
      and Nutrition Examination Survey (KNHANES) 2008 to 2011 were pooled. They
      reported their gender, age, marital status, education level, employment status,
      income, home ownership, and cohabitation status with their parents. The
      association of living with parents and stress, as well as the gender difference
      in the association, was investigated using propensity score matching and the
      average treatment effect on the treated. Adults with higher education and income,
      not owning a house, or living in larger cities were less likely to live with
      parents. Stress was associated with having children and participating in the
      labor market for both married men and women. Moreover, living with parents was a
      protective factor for stress among husbands, but a risk factor for wives in
      Korea. Gender differences existed in the association between cohabitation with
      parents and stress. Greater stress was related to cohabiting with parents and
      working for married women. 

PMID- 26211935
TI  - Translational Anisotropy and Rotational Diffusion of Gold Nanorods in Colloidal
      Sphere Solutions.
AB  - We studied the translational and rotational diffusion of gold nanorods within a
      rod/sphere composite liquid using fluctuation correlation spectroscopy (FCS). The
      nanorods of length L ~ 60 nm and diameter d ~ 17 nm were used at a fixed
      concentration of ~1 pM. The concentration of colloidal Ludox spheres (size ~ 26
      nm) was varied up to a volume fraction of phi = 0.3 or approximately 7
      spheres/L(3). Our experiments showed significant translational anisotropy as the
      sphere concentration was increased. The translational diffusion parallel to the
      rod axis (D(T?)) followed very close to the bulk viscosity of the solution.
      However, the diffusion normal to the rod axis (D(T?)) experienced a significantly
      higher frictional force. For volume fraction phi > 0.1 a slightly modified caging
      theory by Pecora and Deutch could explain the rotational diffusion of the rods
      very well. At low volume fraction the agreement is poor, which we interpreted as
      modification of the local ordering of the spheres, which can affect the rod
      rotation.

PMID- 26211936
TI  - Total Analysis of Microcystins in Fish Tissue Using Laser Thermal Desorption
      Atmospheric Pressure Chemical Ionization-High-Resolution Mass Spectrometry (LDTD
      APCI-HRMS).
AB  - Microcystins (MCs) are cyanobacterial toxins encountered in aquatic environments
      worldwide. Over 100 MC variants have been identified and have the capacity to
      covalently bind to animal tissue. This study presents a new approach for cell
      bound and free microcystin analysis in fish tissue using sodium hydroxide as a
      digestion agent and Lemieux oxidation to obtain the 2-methyl-3-methoxy-4
      phenylbutyric acid (MMPB) moiety, common to all microcystin congeners. The use of
      laser diode thermal desorption-atmospheric pressure chemical ionization coupled
      with Q-Exactive mass spectrometry (LDTD-APCI-HRMS) led to an analysis time of
      approximately 10 s per sample and high-resolution detection. Digestion/oxidation
      and solid phase extraction recoveries ranged from 70 to 75% and from 86 to 103%,
      respectively. Method detection and quantification limits values were 2.7 and 8.2
      MUg kg(-1), respectively. Fish samples from cyanobacteria-contaminated lakes were
      analyzed, and concentrations ranging from 2.9 to 13.2 MUg kg(-1) were reported. 

PMID- 26211937
TI  - Evidence for a vestigial pinna-orienting system in humans.
AB  - Although some people can voluntarily move their ears, overt reflexive control of
      the pinnae has been lost during the course of primate evolution. Humans and apes
      do not move their ears to express emotion, they do not defensively retract them
      when startled, and they do not point them at novel, salient, or task-relevant
      stimuli. Nevertheless, it is the thesis of this review that neural circuits for
      pinna orienting have survived in a purely vestigial state for over 25 million
      years. There are three lines of evidence: (1) Shifting the eyes hard to one side
      is accompanied by electromyographic (EMG) activity in certain ear muscles and by
      a barely visible (2-3 mm) curling of the dorsal edge of the pinna. (2) The
      capture of attention by a novel, unexpected sound emanating from behind and to
      one side has been found to trigger a weak EMG response in the muscle behind the
      corresponding ear. (3) Reflexive EMG bursts recorded during a selective attention
      task suggested that subjects were unconsciously attempting to orient their ears
      toward the relevant sounds. In addition to pinna orienting, the possibility that
      pinna startle might have survived in a vestigial state is also considered. It is
      suggested that the postauricular reflex to sudden, intense sounds constitutes a
      vestigial startle response, but that the reflex arc is dominated by a pathway
      that bypasses the main organizing center for startle. 

PMID- 26211938
TI  - Shared additive genetic influences on DSM-IV criteria for alcohol dependence in
      subjects of European ancestry.
AB  - BACKGROUND AND AIMS: Genetic studies of alcohol dependence (AD) have identified
      several candidate loci and genes, but most observed effects are small and
      difficult to reproduce. A plausible explanation for inconsistent findings may be
      a violation of the assumption that genetic factors contributing to each of the
      seven DSM-IV criteria point to a single underlying dimension of risk. Given that
      recent twin studies suggest that the genetic architecture of AD is complex and
      probably involves multiple discrete genetic factors, the current study employed
      common single nucleotide polymorphisms in two multivariate genetic models to
      examine the assumption that the genetic risk underlying DSM-IV AD is unitary.
      DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: AD symptoms and genome-wide single
      nucleotide polymorphism (SNP) data from 2596 individuals of European descent from
      the Study of Addiction: Genetics and Environment were analyzed using genomic
      relatedness-matrix restricted maximum likelihood. DSM-IV AD symptom covariance
      was described using two multivariate genetic factor models. FINDINGS: Common SNPs
      explained 30% (standard error=0.136, P=0.012) of the variance in AD diagnosis.
      Additive genetic effects varied across AD symptoms. The common pathway model
      approach suggested that symptoms could be described by a single latent variable
      that had a SNP heritability of 31% (0.130, P=0.008). Similarly, the exploratory
      genetic factor model approach suggested that the genetic variance/covariance
      across symptoms could be represented by a single genetic factor that accounted
      for at least 60% of the genetic variance in any one symptom. CONCLUSION: Additive
      genetic effects on DSM-IV alcohol dependence criteria overlap. The assumption of
      common genetic effects across alcohol dependence symptoms appears to be a valid
      assumption.

PMID- 26211939
TI  - Comparison of scoring systems for nonvariceal upper gastrointestinal bleeding: a
      multicenter prospective cohort study.
AB  - BACKGROUND AND AIM: The Glasgow-Blatchford score (GBS) and Rockall score (RS) are
      widely used to assess risk in patients with upper gastrointestinal bleeding
      (UGIB). We compared both scoring systems and evaluated their clinical usefulness.
      METHODS: Between February 2011 and December 2013, 1584 patients with nonvariceal
      UGIB were included in the study. A prospective study was conducted to compare the
      performance of the GBS, pre-RS, and full RS. We compared the performance of these
      scores using receiver operating characteristic curves. RESULTS: For prediction of
      the need for hospital-based intervention, the GBS was similar to the full RS
      (area under the receiver operating characteristic curves [AUROC] 0.705 vs 0.727;
      P = 0.282) and superior to the pre-RS (AUROC 0.705 vs 0.601; P < 0.0001). In
      predicting death, the full RS was superior to the GBS (AUROC 0.758 vs 0.644; P =
      0.0006) and similar to the pre-RS (AUROC 0.758 vs 0.754; P = 0.869). In
      predicting rebleeding, the full RS was superior to both GBS (AUROC 0.642 vs
      0.585; P = 0.031) and pre-RS (AUROC 0.642 vs 0.593; P = 0.0003). Of 1584
      patients, 13 (0.8%) scored 0 on the GBS. Therapeutic intervention was not
      performed in any of these patients. CONCLUSIONS: The GBS is more useful than the
      pre-RS for predicting the need for hospital-based intervention. A cutoff value of
      0 for low-risk patients who might be suitable for outpatient management is
      useful. The full RS is helpful in predicting death. None of the systems
      accurately predict rebleeding with a low AUROC. ( CLINICAL TRIAL:
      cris.nih.go.kr/KCT0000514).

PMID- 26211940
TI  - Safety & pK of IV loading dose of lacosamide in the ICU.
AB  - A restrospective review of patients treated in the ICU for refractory status
      epilepticus who had received an initial IV loading dose of lacosamide (LCS) was
      performed. A total of 142 patients were identified. The first 34 patients
      received 400mg which by weight-based measurement ranged from 2 to 11 mg/kg.
      Higher mg/kg dosing had been used subsequently with doses up to 13 mg/kg. No
      patient required reduction in rate or cessation of infusion. Initiation of
      pressor agents was not needed during the infusion of the loading dose.
      Postinfusion LCS blood levels were drawn, and dosing of 10-12 mg/kg and higher
      resulted in blood levels above 15 MUg/ml while doses of 2-6 mg/kg resulted in
      levels below 10 MUg/ml. We conclude that a weight-based loading dose of 10-12
      mg/kg at an infusion rate of 0.4 mg/kg/min is safe and will produce levels of 15
      MUg/ml and higher. This article is part of a Special Issue entitled "Status
      Epilepticus".

PMID- 26211941
TI  - Progranulin levels in status epilepticus as a marker of neuronal recovery and
      neuroprotection.
AB  - INTRODUCTION: Recently, a mouse model showed that progranulin, a mediator in
      neuroinflammation and a neuronal growth factor, was elevated in the hippocampus
      after status epilepticus (SE). This elevated level might mirror compensating
      neuronal mechanisms after SE. Studies concerning neuronal recovery and
      neuroprotective mechanisms after SE in humans are scarce, so we tested for
      progranulinin the cerebrospinal fluid (CSF) after various types of SE. METHOD: We
      performed a retrospective analysis of progranulin levels in CSF in patients (n =
      24) who underwent lumbar puncture as part of diagnostic workup after having SE
      and in patients after having one single tonic-clonic seizure who comprised the
      control group (n = 8). RESULTS: In our group with SE, progranulin levels in CSF
      were not significantly elevated compared to our control group. Furthermore, there
      was no correlation between progranulin levels and the time interval between
      lumbar puncture and SE. Additionally, in cases of higher CSF progranulin levels,
      we found no impact on the clinical outcome after SE. CONCLUSION: Although our
      cohort is heterogeneous and not fully sufficient, we conclude that progranulin in
      CSF is not elevated after SE in our cohort. Therefore, our results do not suggest
      a change in cerebral progranulin metabolism as a possible neuroregenerative or
      neuroprotective mechanism in humans after SE in acute and subacute phases. A
      larger cohort study is needed to further strengthen this result. This article is
      part of a Special Issue entitled "Status Epilepticus".

PMID- 26211943
TI  - Changes in the approach to acute diverticulitis.
AB  - Acute diverticulitis (AD) is one of the most common acute admission diagnoses for
      general surgery, and its prevalence is increasing, in part due to the ageing
      population. Currently, most patients who present to a tertiary hospital are
      admitted for a period of treatment and observation. Simple, safe and cost
      effective strategies for improving our current treatment of this condition will
      be invaluable in providing the most appropriate management for individual
      patients and for reducing the health resources expended on hospital admissions
      and parenteral antibiotics. AD can be categorized as uncomplicated or
      complicated, these two subtypes have a very different clinical course. The
      management of uncomplicated AD has become increasingly conservative, with a focus
      on symptomatic relief and supportive management. Recent research has brought into
      question the need for extended hospital admission and questioned the current use
      of antibiotics. Anti-inflammatory agents that reduce local inflammation in
      uncomplicated AD may be a useful means of reducing damage caused by inflammation
      and aiding earlier resolution of the inflammatory response and associated
      symptoms. Mesalazine is an anti-inflammatory agent that has been trialled in
      uncomplicated AD. Mesalazine has been shown to improve time to resolution of
      endoscopic and histological evidence of inflammation following an episode of AD
      and also reduce the rate of recurrence. In this literature review, we provide an
      overview of recent advances in AD classification, pathophysiology and management,
      and examine the possibility of introducing the use of anti-inflammatory agents in
      the management of uncomplicated AD. 

PMID- 26211942
TI  - The effect of single course high dose dexamethasone on CD28/CTLA-4 balance in the
      treatment of patients with newly diagnosed primary immune thrombocytopenia.
AB  - To evaluate the effect of a single course of high dose dexamethasone (HD-DXM) on
      CD28 and CTLA-4 expression in patients with newly-diagnosed primary immune
      thrombocytopenia (ITP). Twenty-8 ITP patients (18 females and 10 males, age range
      18-65 years, median age 38.5 years) enrolled in this study and 26 healthy
      volunteers (19 women and 7 men, age range 16-66 years, median age 37 years)
      served as a control group. The patients were treated with HD-DXM (40 mg/day) for
      4 consecutive days. CD28 and CTLA-4 expression was assessed by flow cytometry
      once-monthly for 6 months. Plasma levels of the cytokines IFN-gamma and IL-10
      were determined by enzyme-linked immunosorbent assay. One month after treatment,
      a platelet response was observed in 23 (82%) of the patients. The response rates
      over the next 5 months were 71%, 57%, 53%, 46%, and 39%, chronologically. We
      observed a significant decrease in CD28 expression after the first month (34.7 +/
      4.8% vs. 44.5 +/- 4.4% before treatment), after which the CD28 levels gradually
      increased. In contrast, CTLA-4 expression increased after the first month (3.2 +/
      0.5% vs. 0.8 +/- 0.4 before treatment), after which the CTLA-4 levels gradually
      decreased. Similar dynamic changes were seen in the levels of IFN-gamma and IL
      10. The dynamic changes of CD28 and CTLA-4 were consistent with those of IFN
      gamma and IL-10 and with the effectiveness of HD-DXM in the treatment of ITP. Our
      results suggest that a disturbed CD28/CTLA-4 balance may contribute to the
      immunopathogenesis of ITP. 

PMID- 26211944
TI  - Anxiety, anticipation and contextual information: A test of attentional control
      theory.
AB  - We tested the assumptions of Attentional Control Theory (ACT) by examining the
      impact of anxiety on anticipation using a dynamic, time-constrained task.
      Moreover, we examined the involvement of high- and low-level cognitive processes
      in anticipation and how their importance may interact with anxiety. Skilled and
      less-skilled tennis players anticipated the shots of opponents under low- and
      high-anxiety conditions. Participants viewed three types of video stimuli, each
      depicting different levels of contextual information. Performance effectiveness
      (response accuracy) and processing efficiency (response accuracy divided by
      corresponding mental effort) were measured. Skilled players recorded higher
      levels of response accuracy and processing efficiency compared to less-skilled
      counterparts. Processing efficiency significantly decreased under high- compared
      to low-anxiety conditions. No difference in response accuracy was observed. When
      reviewing directional errors, anxiety was most detrimental to performance in the
      condition conveying only contextual information, suggesting that anxiety may have
      a greater impact on high-level (top-down) cognitive processes, potentially due to
      a shift in attentional control. Our findings provide partial support for ACT;
      anxiety elicited greater decrements in processing efficiency than performance
      effectiveness, possibly due to predominance of the stimulus-driven attentional
      system. 

PMID- 26211945
TI  - Leishmaniasis: diagnostic issues in Europe.
AB  - Leishmaniasis is a parasitic disease with clinical presentations that vary from
      asymptomatic infection to cutaneous, mucocutaneous or visceral disease. Recent
      epidemiological studies have shown an increased prevalence in Europe largely
      caused by an increase in international travel, difficulty eradicating leishmanial
      infection in AIDS patients, and the use of immunosuppressive medications.
      Clinical diagnosis may be challenging, and parasitological diagnosis entails the
      use of invasive procedures which may be unrevealing in the immunosuppressed. A
      number of less invasive tests for the detection of anti-leishmanial antibodies or
      leishmanial antigen are available but their sensitivity and specificity may vary
      with the infective species and results have to be interpreted in light of the
      clinical presentation. The availability of polymerase chain reaction assays
      amplifying leishmanial genetic material has been a major step forward in
      improving the diagnosis of leishmanial disease and the response to treatment. 

PMID- 26211946
TI  - Tedizolid for treatment of acute bacterial skin and skin structure infections.
AB  - Tedizolid is a newly approved drug of the oxazolidinone class. It has high in
      vitro activity against Gram-positive bacteria, including multidrug-resistant
      strains. Peak plasma concentration of tedizolid is obtained within 3 h of oral
      dosing (PO), with high bioavailability. Tedizolid is mostly metabolized via the
      liver, and is excreted in feces in the form of a sulfate conjugate. Tedizolid 200
      mg taken once daily demonstrated non-inferior efficacy and a good safety profile
      in patients with acute bacterial skin and skin structure infections. Results of
      two pivotal Phase III clinical trials showed that 6 days of 200 mg tedizolid PO
      or sequential intravenous (IV)/PO once-daily treatment was non-inferior to 10
      days of 600 mg linezolid PO or sequential IV/PO twice-daily treatment at 48-72 h
      (primary end point) and at the test-of-cure in patients with acute bacterial skin
      and skin structure infections. The Phase II and Phase III trials also
      demonstrated that tedizolid was well tolerated. 

PMID- 26211947
TI  - Sitagliptin in type 2 diabetes mellitus: Efficacy after five years of therapy.
AB  - The aim of this study was to investigate whether the positive effects of
      sitagliptin were maintained even after five years of treatment. Starting from
      2008 to today, we treated 624 patients, not well controlled by current therapy,
      with the addition of sitagliptin 100 mg/die. Patients included 216 subjects
      treated with metformin, 206 treated with sulfonylureas, and 202 treated with
      pioglitazone. Sitagliptin was added to metformin, sulfonylureas and pioglitazone
      in monotherapy, respectively, and the data were compared with those of 620
      patients treated with sulfonylureas+metformin, pioglitazone+metformin and
      pioglitazone+sulfonylureas matched for age, sex, diabetes duration. We recorded
      that the addition of sitagliptin to current hypoglycemic therapy led to a
      reduction of HbA1c similar to that obtained with sulfonylureas after two years.
      After five years of treatment, changes in HbA1c suggest a better glycemic control
      over the long term with sitagliptin compared to other treatments, particularly
      when compared with sulfonylureas. The other parameters evaluated as fasting
      plasma glucose, post-prandial plasma glucose and insulin levels, confirm the
      trends observed for the value of HbA1c. Regarding BMI, it increased with
      sulfonylureas and pioglitazone compared to sitagliptin. Patients treated with
      sulfonylureas had a higher incidence of hypoglycemia compared to sitagliptin. In
      conclusion, sitagliptin seems to maintain its positive effects on glycemia and
      fasting plasma insulin on the long term.

PMID- 26211948
TI  - Aiming for allosterism: Evaluation of allosteric modulators of CB1 in a neuronal
      model.
AB  - Cannabinoid pharmacology has proven nettlesome with issues of promiscuity a
      common theme among both agonists and antagonists. One recourse is to develop
      allosteric ligands to modulate cannabinoid receptor signaling. Cannabinoids have
      come late to the allosteric table. The 'first-generation' negative and positive
      allosteric modulators (NAMs and PAMs) represent an important first effort.
      However, most studies have relied on synthetic agonists, often tested in over
      expression systems rather than a defined neuronal model system that utilizes
      endogenously synthesized and released cannabinoids. We have systematically
      examined first-generation NAMs and a PAM on endocannabinoid modulation of
      synaptic transmission in cultured autaptic hippocampal neurons. These neurons
      exhibit CB1 and 2-arachidonoyl glycerol (2-AG)-mediated depolarization induced
      suppression of excitation (DSE) and therefore serve as a model to test CB1
      modulators in a neuronal model of endogenous cannabinoid signaling. We find
      ORG27569, PSNCBAM-1, and PEPCAN12 attenuate DSE and do not directly inhibit CB1
      receptors. Of these PSNCBAM-1 is the most efficacious while PEPCAN12 has the
      distinction of being an endogenous NAM. The reported NAMs pregnenolone and
      hemopressin as well as the reported PAM lipoxin A4 are without effect in this
      model of endocannabinoid signaling. In summary, three of the allosteric
      modulators evaluated function in a manner consistent with allosterism in a
      neuronal 2-AG-based model of endogenous cannabinoid signaling. 

PMID- 26211949
TI  - Interactions of pannexin 1 with NMDA and P2X7 receptors in central nervous system
      pathologies: Possible role on chronic pain.
AB  - Pannexin 1 (Panx1) is a glycoprotein that acts as a membrane channel in a wide
      variety of tissues in mammals. In the central nervous system (CNS) Panx1 is
      expressed in neurons, astrocytes and microglia, participating in the
      pathophysiology of some CNS diseases, such as epilepsy, anoxic depolarization
      after stroke and neuroinflammation. In these conditions Panx1 acts as an
      important modulator of the neuroinflammatory response, by secreting ATP, by
      interacting with the P2X7 receptor (P2X7R), and as an amplifier of NMDA receptor
      (NMDAR) currents, particularly in conditions of pathological neuronal
      hyperexcitability. Here, we briefly reviewed the current evidences that support
      the interaction of Panx1 with NMDAR and P2X7R in pathological contexts of the
      CNS, with special focus in recent data supporting that Panx1 is involved in
      chronic pain signaling by interacting with NMDAR in neurons and with P2X7R in
      glia. The participation of Panx1 in chronic pain constitutes a novel topic for
      research in the field of clinical neurosciences and a potential target for
      pharmacological interventions in chronic pain. 

PMID- 26211950
TI  - Chemerin: A comprehensive review elucidating the need for cardiovascular
      research.
AB  - When chemerin was discovered in 1997, it was relegated to being a protein
      associated with the normal skin function contrasting the setting of psoriasis.
      However, with the discovery of multiple receptors for the chemerin protein and a
      vast collection of associations with various pathologies, chemerin has global
      influence capable of regulating chemotactic, adipokine, autocrine/paracrine,
      adipogenic, angiogenic, and reproductive functions. These individual abilities of
      chemerin are important for understanding its basic pharmacology and physiology,
      but application of these principles to human pathology relies on the ability of
      scientists and physicians to view this protein from a much wider, all
      encompassing angle. A global participant in the action of chemerin is the
      cardiovascular system (CVS). Although the CVS may not have as many direct
      interactions (e.g. smooth muscle in endothelium) with chemerin as it does
      indirect (e.g. chemerin activation in the lumen by proteases), our basic
      understanding of the CVS and its relation to chemerin is necessary to form a
      proper grasp of its individual actions and make the applications to pathology.
      This review provides a fundamental, yet comprehensive review of chemerin that
      inherently identifies the CVS as a necessary link between chemerin and its
      associated pathologies, but also calls for basic cardiovascular research as the
      solution to this chasm between knowledge and application. 

PMID- 26211952
TI  - Characterization of the CYP2D6 drug metabolizing phenotypes of the Chilean
      mestizo population through polymorphism analyses.
AB  - We tested the influence of four polymorphisms and gene duplication in CYP2D6 on
      in vivo enzyme activity in a Chilean mestizo population in order to identify the
      most relevant genetic profiles that account for observed phenotypes in this
      ethnic group. CYP2D6*2 (2850C>T), *3 (2549A>del), *4 (1846G>A), *17 (1023C>T) and
      gene duplication were determined by PCR-RFLP or PCRL in a group of 321 healthy
      volunteers. Individuals with different variant alleles were phenotyped by
      determining debrisoquine 4-hydroxylase activity as a metabolic ratio (MR) using a
      validated HPLC assay. Minor allele frequencies were 0.41, 0.01, 0.12 and 0.00 for
      CYP2D6*2, *3, *4 and *17 variants, respectively, and the duplication frequency
      was 0.003. Genotype analysis correlated with phenotypes in 18 of 23 subjects
      (78.3%). 11 subjects were extensive metabolizers (EM), 8 were intermediate
      metabolizers (IM), 2 were poor metabolizers (PM) and 2 were ultra-rapid
      metabolizers (UM) which is fairly coincident with expected phenotypes metabolic
      ratios ranged from 0.11 to 126.41. The influence of CYP2D6*3 was particularly
      notable, although only heterozygote carriers were present in our population.
      Individuals homozygous for *4 were always PM. As expected, the only subject with
      gene duplication was UM. In conclusion, there was a clear effect of genotype on
      observed CYP2D6 activity. Classification of EM, PM and UM through genotyping was
      useful to characterize CYP2D6 phenotype in the Chilean mestizo population. 

PMID- 26211951
TI  - Connexin hemichannels influence genetically determined inflammatory and
      hyperproliferative skin diseases.
AB  - Connexin mutations underlie numerous human genetic diseases. Several connexin
      genes have been linked to skin diseases, and mechanistic studies have indicated
      that a gain of abnormal channel function may be responsible for pathology. The
      topical accessibility of the epidermal connexins, the existence of several mouse
      models of human skin disease, and the ongoing identification of pharmacological
      inhibitors targeting connexins provide an opportunity to test new therapeutic
      approaches. 

PMID- 26211959
TI  - Bioprospecting glacial ice for plant growth promoting bacteria.
AB  - Glaciers harbor a wide diversity of microorganisms, metabolically versatile,
      highly tolerant to multiple environmental stresses and potentially useful for
      biotechnological purposes. Among these, we hypothesized the presence of bacteria
      able to exhibit well-known plant growth promoting traits (PGP). These kinds of
      bacteria have been employed for the development of commercial biofertilizers;
      unfortunately, these biotechnological products have proven ineffective in colder
      climates, like the ones prevailing in mountainous ecosystems. In the present
      work, we prospected glacial ice collected from two small tropical glaciers,
      located above 4.900 m in the Venezuelan Andes, for cold-active PGP bacteria. The
      initial screening strategy allowed us to detect the best inorganic-P solubilizers
      at low temperatures, from a sub-sample of 50 bacterial isolates. Solubilization
      of tricalcium phosphate, aluminum- and iron-phosphate, occurred in liquid
      cultures at low temperatures and was dependent on medium acidification by
      gluconic acid production, when bacteria were supplied with an appropriate source
      of carbon. Besides, the isolates were psychrophilic and in some cases exhibited a
      broad range of growth-temperatures, from 4  degrees C to 30  degrees C.
      Additional PGP abilities, including phytohormone- and HCN production, siderophore
      excretion and inhibition of phytopathogens, were confirmed in vitro. Nucleotidic
      sequence analysis of 16S rRNA genes allowed us to place the isolates within the
      Pseudomonas genus. Our results support the possible use of these strains to
      develop cold-active biofertilizers to be used in mountainous agriculture.

PMID- 26211958
TI  - piggyBac-ing models and new therapeutic strategies.
AB  - DNA transposons offer an efficient nonviral method of permanently modifying the
      genomes of mammalian cells. The piggyBac transposon system has proven effective
      in genomic engineering of mammalian cells for preclinical applications, including
      gene discovery, simultaneous multiplexed genome modification, animal
      transgenesis, gene transfer in vivo achieving long-term gene expression in
      animals, and the genetic modification of clinically relevant cell types, such as
      induced pluripotent stem cells and human T lymphocytes. piggyBac has many
      desirable features, including seamless excision of transposons from the genomic
      DNA and the potential to target integration events to desired DNA sequences. In
      this review, we explore these recent applications and also highlight the unique
      advantages of using piggyBac for developing new molecular therapeutic strategies.

PMID- 26211960
TI  - Diversity of bacteria, archaea and protozoa in a perchlorate treating bioreactor.
AB  - A microbial consortium reducing high level of perchlorate was developed and in a
      fed batch bioreactor using acetate as substrate perchlorate was reduced at 0.25
      g/g vss. day. Under stable performance, the microbial community structure of the
      reactor was analyzed through molecular and phenotypic methods. The diversity of
      bacteria and archaea were analyzed through whole cell Fluorescence In-Situ
      Hybridization (FISH) and PCR-Denaturing Gradient Gel Electrophoresis (DGGE),
      whereas higher trophic community was analyzed phenotypically. FISH analysis
      revealed the presence of alpha, beta, gamma and delta proteobacteria in the
      sludge, dominated by beta proteobacteria (68.7%). DGGE analysis of bacteria
      revealed the presence of a single known perchlorate reducing bacterium
      Dechloromonas, nitrate reducers like Thaeura and Azoarcus and a number of other
      genera so far not reported as perchlorate or nitrate reducing. The archaea
      community was represented by an acetoclastic methanogen, Methanosaeta
      harundinacea. We have also observed the presence of an acetate consuming
      flagellate, Polytomella sp. in significant number in the reactor. Archaea and
      protozoa community in perchlorate treating bioreactor is reported first time in
      this study and point out further the significance of non perchlorate reducing but
      acetate scavenging microbial groups in acetate fed perchlorate treating reactors.

PMID- 26211961
TI  - The ActP acetate transporter acts prior to the PitA phosphate carrier in
      tellurite uptake by Escherichia coli.
AB  - The tellurium oxyanion tellurite is harmful for most microorganisms. Since its
      toxicity occurs chiefly once the toxicant reaches the intracellular compartment,
      unveiling the toxicant uptake process is crucial for understanding the whole
      phenomenon of tellurium toxicity. While the PitA phosphate transporter is thought
      to be one of the main paths responsible for toxicant entry into Escherichia coli,
      genetic and physiological evidence have identified the ActP acetate carrier as
      the main tellurite importer in Rhodobacter capsulatus. In this work, new
      background on the role of these transporters in tellurite uptake by E. coli is
      presented. It was found that, similar to what occurs in R. capsulatus, ActP is
      able to mediate toxicant entry to this bacterium. Lower reactive oxygen species
      levels were observed in E. coli lacking the actP gene. Antioxidant enzyme
      catalase and fumarase C activity was almost unchanged after short exposure of E.
      coli DeltaactP to sublethal tellurite concentrations, suggesting a low
      antioxidant response. In this strain, tellurite uptake decreased significantly
      during the first 5 min of exposure and inductively coupled plasma optical
      emission spectroscopy assays using an actP-overexpressing strain confirmed that
      this carrier mediates toxicant uptake. Relative gene expression experiments by
      qPCR showed that actP expression is enhanced at short times of tellurite
      exposure, while pitA and pitB genes are induced later. Summarizing, the results
      show that ActP is involved in tellurite entry to E. coli and that its
      participation occurs mainly at early stages of toxicant exposure.

PMID- 26211962
TI  - Escherichia coli 6-phosphogluconate dehydrogenase aids in tellurite resistance by
      reducing the toxicant in a NADPH-dependent manner.
AB  - Exposure to the tellurium oxyanion tellurite (TeO3(2-)) results in the
      establishment of an oxidative stress status in most microorganisms. Usually,
      bacteria growing in the presence of the toxicant turn black because of the
      reduction of tellurite (Te(4+)) to the less-toxic elemental tellurium (Te(0)). In
      vitro, at least part of tellurite reduction occurs enzymatically in a
      nicotinamide dinucleotide-dependent reaction. In this work, we show that TeO3(2-)
      reduction by crude extracts of Escherichia coli overexpressing the zwf gene
      (encoding glucose-6-phosphate dehydrogenase) takes place preferentially in the
      presence of NADPH instead of NADH. The enzyme responsible for toxicant reduction
      was identified as 6-phosphogluconate dehydrogenase (Gnd). The gnd gene showed a
      subtle induction at short times after toxicant exposure while strains lacking gnd
      were more susceptible to the toxicant. These results suggest that both NADPH
      generating enzymes from the pentose phosphate shunt may be involved in tellurite
      detoxification and resistance in E. coli. 

PMID- 26211963
TI  - Potential extra-ribosomal functions of ribosomal proteins in Saccharomyces
      cerevisiae.
AB  - Ribosomal proteins (RPs), are essential components of the ribosomes, the
      molecular machines that turn mRNA blueprints into proteins, as they serve to
      stabilize the structure of the rRNA, thus improving protein biosynthesis. In
      addition, growing evidence suggests that RPs can function in other cellular
      roles. In the present review, we summarize several potential extra-ribosomal
      functions of RPs in ribosomal biogenesis, transcription activity, translation
      process, DNA repair, replicative life span, adhesive growth, and morphological
      transformation in Saccharomyces cerevisiae. However, the future in-depth studies
      are needed to identify these novel secondary functions of RPs in S. cerevisiae. 

PMID- 26211964
TI  - Conjunctively screening of biocontrol agents (BCAs) against fusarium root rot and
      fusarium head blight caused by Fusarium graminearum.
AB  - BACKGROUND AND AIMS: Fusarium root-rot and fusarium head blight are plant
      diseases caused by Fusarium sp. in different growth periods of wheat, bring heavy
      losses to crop production in China. This research is aiming to screen biocontrol
      agents conjunctively for controlling these two diseases at the same time, as well
      as evaluate our previous BCAs (Biological Control Agents) screening strategies in
      more complex situation, considering biocontrol is well concerned as an
      environmental-friendly plant disease controlling method. METHODS: Totally 966
      bacterial isolates were screened from different parts of wheat tissues, of which
      potential biocontrol values were detected according to their abilities in
      antagonism inhibition and secreting extracellular hydrolytic enzyme. Biocontrol
      tests against fusarium root rot and fusarium head blight were carried out on 37
      bacterial isolates with potential biocontrol capacity after pre-selection through
      ARDRA- and BOX-PCR analysis on strains with high assessment points. RESULTS: We
      acquired 10 BCAs with obvious biocontrol efficacy (more than 40%) in greenhouse
      and field tests. Pseudomonas fluorescens LY1-8 performed well in both two tests
      (biocontrol efficacy: 44.62% and 58.31%), respectively. Overall, correlation
      coefficient is 0.720 between assessment values of 37 tested BCA strains and their
      biocontrol efficacy in trails against fusarium root rot; correlation coefficient
      is 0.806 between their assessment values and biocontrol efficacy in trails
      against fusarium head blight. CONCLUSION: We acquired 10 well-performed potential
      BCAs, especially P. fluorescens LY1-8 displayed good biocontrol capacity against
      two different diseases on wheat. Biocontrol efficacies results in both greenhouse
      and field tests showed high positive correlation with assessment values (0.720
      and 0.806), suggesting that the BCAs screening and assessing strategy previously
      developed in our lab is also adaptable for conjunctively screening BCAs for
      controlling both root and shoot diseases on wheat caused by same fungal pathogen.

PMID- 26211965
TI  - Microbial diversity in the deep-sea sediments of Iheya North and Iheya Ridge,
      Okinawa Trough.
AB  - In this study, we analyzed the bacterial and archaeal diversities of the deep-sea
      sediments in Iheya North and Iheya Ridge, Okinawa Trough, using the high
      throughput sequencing technology of Illumina MiSeq 2500 platform. Four samples
      (IN1, IN2, IR1 and IR2) were used in this study, of which IN1 and IN2 were
      located at regions close to and distant, respectively, from the active
      hydrothermal vents in Iheya North, while IR1 and IR2 were located at regions
      close to and distant, respectively, from the active hydrothermal vents in Iheya
      Ridge. The four samples were rich in different metal elements. Sequence analysis
      based on the V3-V4 regions of 16S rDNA gene obtained 170,363 taxon tags,
      including 122,920 bacterial tags and 47,433 archaeal tags, which cover 31 phyla,
      50 classes, 59 orders, 87 families, and 138 genera. Overall, the microbial
      communities in all samples were dominated by bacteria, in which Proteobacteria
      was the largest phylum, followed by Chloroflexi, Firmicutes, Acidobacteria,
      Actinobacteria, Gemmatimonadetes, and Nitrospirae, which together accounted for
      64.6% of the total taxon tags. In contrast to the high bacterial diversities, the
      archaeal diversity was low and dominated by Thaumarchaeota, which accounted for
      22.9% of the total taxon tags. Comparative analysis showed that (i) IN2 and IR2
      exhibited more microbial richness than IN1 and IR1, (ii) IR1 and IR2 exhibited
      higher microbial diversities than IN1 and IN2, (iii) samples from Iheya Ridge and
      Iheya North fell into two groups based on principle component analysis.
      Furthermore, microbes potentially involved in sulfur, nitrogen, and metal
      metabolism and cycling were detected in all samples. These results provide for
      the first time a comparative picture of the microbial diversities in the
      sediments of Iheya North and Iheya Ridge and indicate that geological features
      and distance from active hydrothermal vents likely play important roles in the
      shaping of microbial community structure. 

PMID- 26211966
TI  - Identification of genes induced by Fusarium graminearum inoculation in the
      resistant durum wheat line Langdon(Dic-3A)10 and the susceptible parental line
      Langdon.
AB  - The wheat recombinant chromosome inbred line LDN(Dic-3A)10, obtained through
      introgression of a Triticum dicoccoides disomic chromosome 3A fragment into
      Triticum turgidum spp. durum var. Langdon, is resistant to fusarium head blight
      (FHB) caused by Fusarium graminearum. To identify genes involved in FHB
      resistance, we used a cDNA-AFLP approach to compare gene expression between
      LDN(Dic-3A)10 and the susceptible parental line LDN at different time points post
      inoculation. In total, 85 out of the ~ 500 transcript-derived fragments (TDFs)
      were found to be differentially expressed: 36 and 19% were upregulated in LDN(Dic
      3A)10 and LDN, respectively, whereas 45% were induced in both genotypes. Several
      of the cloned TDFs showed similarity to proteins involved in specific recognition
      of plant pathogens or associated with early responses to infection. Some TDFs
      specific to the inoculation response did not show similarity to characterized
      proteins. The availability of T. aestivum genome sequences allowed the in silico
      mapping of 28 TDFs and the acquirement of the corresponding gene sequences and,
      in some cases, their regulatory regions. Analysis of promoter regions revealed
      the potential existence of shared transcription regulation mechanisms. For
      instance, three TDF-associated genes contained binding sites for WRKY
      transcription factors, which have been implicated in the regulation of genes
      associated with pathogen defense, and three for abscisic acid-responsive element
      (ABRE). Collectively, our results revealed specific pathogen recognition in the
      interactions of LDN and LDN(Dic-3A)10 with F. graminearum. Such recognition leads
      to changes in the expression of several transcripts, attributable to the presence
      of the wheat QTL Qfhs.ndsu-3AS.

PMID- 26211967
TI  - The immune response of bovine mammary epithelial cells to live or heat
      inactivated Mycoplasma bovis.
AB  - Mycoplasma bovis is an emerging bacterial agent causing bovine mastitis. Although
      these cell wall-free bacteria lack classical virulence factors, they are able to
      activate the immune system of the host. However, effects on the bovine mammary
      immune system are not yet well characterized and detailed knowledge would improve
      the prevention and therapy of mycoplasmal mastitis. The aim of this study was to
      investigate the immunogenic effects of M. bovis on the mammary gland in an
      established primary bovine mammary epithelial cell (bMEC) culture system. Primary
      bMEC of four different cows were challenged with live and heat-inactivated M.
      bovis strain JF4278 isolated from acute bovine mastitis, as well as with the type
      strain PG45. The immune response was evaluated 6 and 24h after mycoplasmal
      challenge by measuring the relative mRNA expression of selected immune factors by
      quantitative PCR. M. bovis triggered an immune response in bMEC, reflected by the
      upregulation of tumor necrosis factor-alpha, interleukin(IL)-1beta, IL-6, IL-8,
      lactoferrin, Toll-like receptor-2, RANTES, and serum amyloid A mRNA.
      Interestingly, this cellular reaction was only observed in response to live, but
      not to heat-inactivated M. bovis, in contrast to other bacterial pathogens of
      mastitis such as Staphylococcus aureus. This study provides evidence that bMEC
      exhibit a strong inflammatory reaction in response to live M. bovis. The lack of
      a cellular response to heat-inactivated M. bovis supports the current hypothesis
      that mycoplasmas activate the immune system through secreted secondary
      metabolites. 

PMID- 26211968
TI  - Presence of leptospires on genital tract of mares with reproductive problems.
AB  - Leptospirosis is a zoonotic disease of global importance, and has a worldwide
      distribution. Equine leptospirosis is commonly manifested by recurrent uveitis,
      reproductive disorders, as abortions, embryonic absorption, stillbirth and the
      birth of weak foals. The aim of this study was to verify the presence of
      Leptospira sp or its DNA in genital tract of mares with reproductive problems. A
      total of 38 mares with reproductive problems were studied. All the mares were
      sampled for blood (for serology), urine (for culturing and qPCR), vaginal fluid
      VF and endometrial biopsy-EB (for culturing, qPCR and indirect
      immunofluorescence). PCRs products were sequenced for secY gene. Seventeen
      (44.7%) serum samples were reactive, predominantly against serogroups Australis
      (76.4%) and Pomona (23.6%). No positive culture was obtained, but DNA was
      detected by qPCR on urine samples (26.3%), VF (44.7%) and EB (18.4%) collected 2
      months or longer following diagnosis of early fetal death and endometritis.
      Leptospira cell aggregations were visible by indirect immunofluorescence on 57.1%
      (4/7) EBs and 17.6% (3/17) VFs. A total of 18 amplicons showed interpretable
      sequences. Out of those 18 amplicons, 15 presented 100% of identity with the
      species L. interrogans (sv Bratislava and Pomona), while three were L.
      borgpertersenii. This study suggests the presence of leptospires in the uterus of
      mares with reproductive problems. Moreover, serology was shown not to be
      indicated for the diagnosis of presumptive Leptospira infection in early
      gestation. The most common agent of the genital infection in those mares was L.
      interrogans, most probably sg Australis. 

PMID- 26211969
TI  - Using an Individual Procedure Score Before and After the Advanced Surgical Skills
      Exposure for Trauma Course Training to Benchmark a Hemorrhage-Control Performance
      Metric.
AB  - OBJECTIVE: Test with an individual procedure score (IPS) to assess whether an
      unpreserved cadaver trauma training course, including upper and lower limb
      vascular exposure, improves correct identification of surgical landmarks,
      underlying anatomy, and shortens time to vascular control. DESIGN: Prospective
      study of performance of 3 vascular exposure and control procedures (axillary,
      brachial, and femoral arteries) using IPS metrics by 2 colocated and trained
      evaluators before and after training with the Advanced Surgical Skills Exposure
      for Trauma (ASSET) course. IPS, including identification of anatomical landmarks,
      incisions, underlying structures, and time to completion of each procedure was
      compared before and after training using repeated measurement models. SETTING:
      Audio-video instrumented cadaver laboratory at University of Maryland School of
      Medicine. PARTICIPANTS: A total of 41 second to sixth year surgical residents
      from surgical programs throughout Mid-Atlantic States who had not previously
      taken the ASSET course were enrolled, 40 completed the pre- and post-ASSET
      performance evaluations. RESULTS: After ASSET training, all components of IPS
      increased and time shortened for each of the 3 artery exposures. Procedure steps
      performed correctly increased 57%, anatomical knowledge increased 43% and skin
      incision to passage of a vessel loop twice around the correct vessel decreased by
      a mean of 2.5 minutes. An overall vascular trauma readiness index, a
      comprehensive IPS score for 3 procedures increased 28% with ASSET Training.
      CONCLUSIONS: Improved knowledge of surface landmarks and underlying anatomy is
      associated with increased IPS, faster procedures, more accurate incision
      placement, and successful vascular control. Structural recognition during
      specific procedural steps and anatomical knowledge were key points learned during
      the ASSET course. Such training may accelerate acquisition of specific trauma
      surgery skills to compensate for shortened training hours, infrequent exposure to
      major vascular injuries, or when just-in-time training is necessary. IPS is a
      benchmark for competence in extremity vascular control.

PMID- 26211970
TI  - Long-Range Modulation of PAG1 Expression by 8q21 Allergy Risk Variants.
AB  - The gene(s) whose expression is regulated by allergy risk variants is unknown for
      many loci identified through genome-wide association studies. Addressing this
      knowledge gap might point to new therapeutic targets for allergic disease. The
      aim of this study was to identify the target gene(s) and the functional
      variant(s) underlying the association between rs7009110 on chromosome 8q21 and
      allergies. Eight genes are located within 1 Mb of rs7009110. Multivariate
      association analysis of publicly available exon expression levels from
      lymphoblastoid cell lines (LCLs) identified a significant association between
      rs7009110 and the expression of a single gene, PAG1 (p = 0.0017), 732 kb away.
      Analysis of histone modifications and DNase I hypersensitive sites in LCLs
      identified four putative regulatory elements (PREs) in the region. Chromosome
      conformation capture confirmed that two PREs interacted with the PAG1 promoter,
      one in allele-specific fashion. To determine whether these PREs were functional,
      LCLs were transfected with PAG1 promoter-driven luciferase reporter constructs.
      PRE3 acted as a transcriptional enhancer for PAG1 exclusively when it carried the
      rs2370615:C allergy predisposing allele, a variant in complete linkage
      disequilibrium with rs7009110. As such, rs2370615, which overlaps RelA
      transcription factor (TF) binding in LCLs and was found to disrupt Foxo3a binding
      to PRE3, represents the putative functional variant in this locus. Our studies
      suggest that the risk-associated allele of rs2370615 predisposes to allergic
      disease by increasing PAG1 expression, which might promote B cell activation and
      have a pro-inflammatory effect. Inhibition of PAG1 expression or function might
      have therapeutic potential for allergic diseases.

PMID- 26211972
TI  - Two cellular hypotheses explaining the initiation of ketamine's antidepressant
      actions: Direct inhibition and disinhibition.
AB  - A single, low dose of ketamine evokes antidepressant actions in depressed
      patients and in patients with treatment-resistant depression (TRD). Unlike
      classic antidepressants, which regulate monoamine neurotransmitter systems,
      ketamine is an antagonist of the N-methyl-D-aspartate (NMDA) family of glutamate
      receptors. The effectiveness of NMDAR antagonists in TRD unveils a new set of
      targets for therapeutic intervention in major depressive disorder (MDD) and TRD.
      However, a better understanding of the cellular mechanisms underlying these
      effects is required for guiding future therapeutic strategies, in order to
      minimize side effects and prolong duration of efficacy. Here we review the
      evidence for and against two hypotheses that have been proposed to explain how
      NMDAR antagonism initiates protein synthesis and increases excitatory synaptic
      drive in corticolimbic brain regions, either through selective antagonism of
      inhibitory interneurons and cortical disinhibition, or by direct inhibition of
      cortical pyramidal neurons. This article is part of the Special Issue entitled
      'Synaptopathy--from Biology to Therapy'.

PMID- 26211971
TI  - A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis.
AB  - Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We
      previously conducted a genome-wide association study (GWAS) and detected two loci
      associated with AIS. To identify additional loci, we extended our GWAS by
      increasing the number of cohorts (2,109 affected subjects and 11,140 control
      subjects in total) and conducting a whole-genome imputation. Through the extended
      GWAS and replication studies using independent Japanese and Chinese populations,
      we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 * 10(-13);
      odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of
      BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression
      quantitative trait loci data suggested that the associated SNPs have the
      potential to regulate the BNC2 transcriptional activity and that the
      susceptibility alleles increase BNC2 expression. We identified a functional SNP,
      rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a
      transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity
      than the non-susceptibility allele. BNC2 overexpression produced body curvature
      in developing zebrafish in a gene-dosage-dependent manner. Our results suggest
      that increased BNC2 expression is implicated in the etiology of AIS.

PMID- 26211973
TI  - Antidiabetic drugs restore abnormal transport of amyloid-beta across the blood
      brain barrier and memory impairment in db/db mice.
AB  - Previous studies have shown significant changes in amyloid-beta (Abeta) transport
      across the blood-brain barrier (BBB) under diabetic conditions with
      hypoinsulinemia, which is involved in diabetes-associated cognitive impairment.
      Present study employed db/db mice with hyperinsulinemia to investigate changes in
      Abeta transport across the BBB, hippocampal synaptic plasticity, and restorative
      effects of antidiabetic drugs. Our results showed that db/db mice exhibited
      similar changes in Abeta transport across the BBB to that of insulin-deficient
      mice. Chronic treatment of db/db mice with antidiabetic drugs such as metformin,
      glibenclamide and insulin glargine significantly decreased Abeta influx across
      the BBB determined by intra-arterial infusion of (125)I-Abeta(1-40), and
      expression of the receptor for advanced glycation end products (RAGE)
      participating in Abeta influx. Insulin glargine, but not, metformin or
      glibenclamide increased Abeta efflux across the BBB determined by stereotaxic
      intra-cerebral infusion of (125)I-Abeta(1-40), and expression of the low-density
      lipoprotein receptor related protein 1 (LRP1) participating in Abeta efflux.
      Moreover, treatment with these drugs significantly decreased hippocampal Abeta(1
      40) or Abeta(1-42) and inhibited neuronal apoptosis. The drugs also ameliorated
      memory impairment confirmed by improved performance on behavioral tasks. However,
      insulin glargine or glibenclamide, but not metformin, restored hippocampal
      synaptic plasticity characterized by enhancing in vivo long-term potentiation
      (LTP). Further study found that these three drugs significantly restrained NF
      kappaB, but only insulin glargine enhanced peroxisome proliferator-activated
      receptor gamma (PPARgamma) activity at the BBB in db/db mice. Our data indicate
      that the antidiabetic drugs can partially restore abnormal Abeta transport across
      the BBB and memory impairment under diabetic context.

PMID- 26211974
TI  - Cross-talk between metabotropic glutamate receptor 7 and beta adrenergic receptor
      signaling at cerebrocortical nerve terminals.
AB  - The co-existence of presynaptic G protein coupled receptors, GPCRs, has received
      little attention, despite the fact that interplay between the signaling pathways
      activated by such receptors may affect the neurotransmitter release. Using
      immunocytochemistry and immuhistochemistry we show that mGlu7 and beta-adrenergic
      receptors are co-expressed in a sub-population of cerebrocortical nerve
      terminals. mGlu7 receptors readily couple to pathways that inhibit glutamate
      release. We found that when mGlu7 receptors are also coupled to pathways that
      enhance glutamate release by prolonged exposure to agonist, and beta-adrenergic
      receptors are also activated, a cross-talk between their signaling pathways
      occurs that affect the overall release response. This interaction is the result
      of mGlu7 receptors inhibiting the adenylyl cyclase activated by beta adrenergic
      receptors. Thus, blocking Gi/o proteins with pertussis toxin provokes a further
      increase in release after receptor co-activation which is also observed after
      activating beta-adrenergic receptor signaling pathways downstream of adenylyl
      cyclase with the cAMP analog Sp8Br or 8pCPT-2-OMe-cAMP (a specific activator of
      the guanine nucleotide exchange protein directly activated by cAMP, EPAC). Co
      activation of mGlu7 and beta-adrenergic receptors also enhances PLC-dependent
      accumulation of IP1 and the translocation of the active zone protein Munc13-1 to
      the membrane, indicating that release potentiation by these receptors involves
      the modulation of the release machinery. 

PMID- 26211975
TI  - Canalization of genetic and pharmacological perturbations in developing primary
      neuronal activity patterns.
AB  - The function of the nervous system depends on the integrity of synapses and the
      patterning of electrical activity in brain circuits. The rapid advances in genome
      sequencing reveal a large number of mutations disrupting synaptic proteins, which
      potentially result in diseases known as synaptopathies. However, it is also
      evident that every normal individual carries hundreds of potentially damaging
      mutations. Although genetic studies in several organisms show that mutations can
      be masked during development by a process known as canalization, it is unknown if
      this occurs in the development of the electrical activity in the brain. Using
      longitudinal recordings of primary cultured neurons on multi-electrode arrays
      from mice carrying knockout mutations we report evidence of canalization in
      development of spontaneous activity patterns. Phenotypes in the activity patterns
      in young cultures from mice lacking the Gria1 subunit of the AMPA receptor were
      ameliorated as cultures matured. Similarly, the effects of chronic
      pharmacological NMDA receptor blockade diminished as cultures matured. Moreover,
      disturbances in activity patterns by simultaneous disruption of Gria1 and NMDA
      receptors were also canalized by three weeks in culture. Additional mutations and
      genetic variations also appeared to be canalized to varying degrees. These
      findings indicate that neuronal network canalization is a form of nervous system
      plasticity that provides resilience to developmental disruption. This article is
      part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.

PMID- 26211976
TI  - A search for presynaptic inhibitory histamine receptors in guinea-pig tissues:
      Further H3 receptors but no evidence for H4 receptors.
AB  - The histamine H4 receptor is coupled to Gi/o proteins and expressed on
      inflammatory cells and lymphoid tissues; it was suggested that this receptor also
      occurs in the brain or on peripheral neurones. Since many Gi/o protein-coupled
      receptors, including the H3 receptor, serve as presynaptic inhibitory receptors,
      we studied whether the sympathetic neurones supplying four peripheral tissues and
      the cholinergic neurones in the hippocampus from the guinea-pig are equipped with
      release-modulating H4 and H3 receptors. For this purpose, we preincubated tissue
      pieces from the aorta, atrium, renal cortex and vas deferens with (3)H
      noradrenaline and hippocampal slices with (3)H-choline and determined the
      electrically evoked tritium overflow. The stimulation-evoked overflow in the five
      superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine,
      which served as a positive control, but not affected by the H4 receptor agonist 4
      methylhistamine. The H3 receptor agonist R-alpha-methylhistamine inhibited
      noradrenaline release in the peripheral tissues without affecting acetylcholine
      release in the hippocampal slices. Thioperamide shifted the concentration
      response curve of histamine in the aorta and the renal cortex to the right,
      yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its
      affinity at other H3 receptors but higher by one log unit than its pKi at the H4
      receptor of the guinea-pig. In conclusion, histamine H4 receptors could not be
      identified in five experimental models of the guinea-pig that are suited for the
      detection of presynaptic inhibitory receptors whereas H3 receptors could be shown
      in the peripheral tissues but not in the hippocampus. This article is part of the
      Special Issue entitled 'Histamine Receptors'.

PMID- 26211977
TI  - Purinergic signaling in Parkinson's disease. Relevance for treatment.
AB  - Purinergic signaling modulates dopaminergic neurotransmission in health and
      disease. Classically adenosine A1 and A2A receptors have been considered key for
      the fine tune control of dopamine actions in the striatum, the main CNS motor
      control center. The main adenosine signaling mechanism is via the cAMP pathway
      but the future will tell whether calcium signaling is relevant in adenosinergic
      control of striatal function. Very relevant is the recent approval in Japan of
      the adenosine A2A receptor antagonist, istradefylline, for use in Parkinson's
      disease patients. Purine nucleotides are also regulators of striatal dopamine
      neurotransmission via P2 purinergic receptors. In parallel to the alpha-synuclein
      hypothesis of Parkinson's disease etiology, purinergic P2X1 receptors have been
      identified as mediators of accumulation of the Lewy-body enriched protein alpha
      synuclein. Of note is the expression in striatum of purinergic-receptor
      containing heteromers that are potential targets of anti-Parkinson's disease
      therapies and should be taken into account in drug discovery programs. This
      article is part of the Special Issue entitled 'Purines in Neurodegeneration and
      Neuroregeneration'.

PMID- 26211978
TI  - Polymerized nano-curcumin attenuates neurological symptoms in EAE model of
      multiple sclerosis through down regulation of inflammatory and oxidative
      processes and enhancing neuroprotection and myelin repair.
AB  - Multiple Sclerosis (MS) is an inflammatory demyelinating disorder of central
      nervous system (CNS). Polyphenol curcumin has been used in traditional medicine
      as an effective drug for a variety of diseases. Different formulations of
      curcumin are introduced to increase its stability and effectiveness. Here we have
      examined the effect of polymerized form of nano-curcumin (PNC) on experimental
      autoimmune encephalomyelitis (EAE) as an animal model of MS. EAE was induced in
      female Lewis rats and PNC or curcumin was daily administrated intraperitonealy
      from day 12-29 post immunization. When the prophylactic effect of PNC was under
      investigation, rats received PNC from the first day of immunization. Treatment
      with PNC resulted in decreased scores of disease in therapeutic and prophylactic
      administration when compared with control group. Staining by luxol fast blue and
      H&E and immuno-staining of lumbar spinal cord cross sections, confirmed a
      significant decrease in the amounts of demyelination, inflammation and BBB
      breaking down. Gene expression studies in lumbar spinal cord showed a corrected
      balance of pro-inflammatory and anti-inflammatory genes expression, decreased
      oxidative stress, improved remyelination and increased progenitor cell markers
      after treatment with PNC. Our results demonstrated an efficient therapeutic
      effect of PNC as an anti-inflammatory and anti-oxidative stress agent, with
      significant effects on the EAE scores and myelin repair mechanisms. 

PMID- 26211979
TI  - Ultrasonography in the intensive care setting can be used to detect changes in
      the quality and quantity of muscle and is related to muscle strength and
      function.
AB  - PURPOSE: This study aimed to (1) document patterns of quadriceps muscle wasting
      in the first 10 days of admission and (2) determine the relationship between
      muscle ultrasonography and volitional measures. MATERIALS AND METHODS: Twenty-two
      adults ventilated for more than 48 hours were included. Sequential quadriceps
      ultrasound images were obtained over the first 10 days and at awakening and
      intensive care unit (ICU) discharge. Muscle strength and function were assessed
      at awakening and ICU discharge. RESULTS: A total of 416 images were analyzed.
      There was a 30% reduction in vastus intermedius (VI) thickness, rectus femoris
      (RF) thickness, and cross-sectional area within 10 days of admission. Muscle
      echogenicity scores increased for both RF and VI muscles by +12.7% and +25.5%,
      respectively (suggesting deterioration in muscle quality). There was a strong
      association between function and VI thickness (r = 0.82) and echogenicity (r = 
      0.77). There was a moderate association between function and RF cross-sectional
      area (r = 0.71). CONCLUSIONS: Muscle wasting occurs rapidly in the ICU setting.
      Ultrasonography is a useful surrogate measure for identifying future impairment.
      Vastus intermedius may be an important muscle to monitor in the future because it
      demonstrated the greatest change in muscle quality and had the strongest
      relationship to volitional measures.

PMID- 26211981
TI  - The Use of Transdermal Therapeutic Systems in Psychiatric Care: A Primer on
      Patches.
AB  - BACKGROUND: Numerous currently available medications that act in the central
      nervous system can be delivered transdermally. Such medications include
      cholinesterase inhibitors for dementia, methylphenidate (MPH) for attention
      deficit hyperactivity disorder, monoamine oxidase inhibitors (MAOIs) for
      depression, dopamine agonists for Parkinson disease and restless leg syndrome,
      and clonidine for attention-deficit hyperactivity disorder and impulse-control
      disorders. OBJECTIVE: This article aims to review the literature related to
      transdermal delivery systems from the perspective of clinical practice and
      research related to their use in the treatment of psychiatric conditions.
      RESULTS: Most of the currently available transdermal systems have psychotropic
      properties or utility in the behavioral health arena and, therefore, are of
      clinical relevance to consultation-liaison psychiatrists or practitioners of
      psychosomatic medicine. We discuss their efficacy and safety profiles. We provide
      a table of these agents and their uses. CONCLUSIONS: Transdermal delivery (i.e.,
      patches) for medicines with psychotropic properties allows mental health
      providers to customize therapy for patients by altering the duration of therapy,
      minimizing first-pass metabolism and the potential for drug-drug interactions,
      and decreasing the risk for gastrointestinal irritation.

PMID- 26211980
TI  - Teaching Collaborative Care in Primary Care Settings for Psychiatry Residents.
AB  - BACKGROUND: Job descriptions for psychiatrists will change significantly over the
      next decade, as psychiatrists will be called on to work as caseload consultants
      to the primary care team. OBJECTIVE: The purpose of this pilot study was to
      examine the effects of an American Association of Directors of Psychiatric
      Residency Training-approved collaborative care curriculum on caseload consulting
      skills among psychiatry residents. METHODS: In 2014, 46 psychiatry residents (5
      postgraduate year 1s, 10 postgraduate year 2s, 22 postgraduate year 3s, and 9
      postgraduate year 4s) from 5 academic psychiatry residency programs in the New
      England area were given the 2-hour pilot collaborative care curriculum.
      Participants were asked to complete an anonymous survey at both the beginning and
      the end of the workshop to rate their comfort level in aspects of collaborative
      care psychiatry (7 items from SBP4 psychiatry milestones) based on a Likert scale
      (1-not at all, 2-slightly, 3-moderately, and 4-extremely). Paired t-test was used
      to examine the difference between pretest and posttest results of residents
      participating in the workshop. RESULTS: The pretest mean score for the group was
      2.9 (standard deviation = 0.44), whereas the posttest mean was 3.51 (standard
      deviation = 0.42), p < 0.0001. Only 15% (n = 7) of residents reported having some
      form of primary care or ambulatory specialty care consultation experience while
      in training. CONCLUSION: This brief collaborative care curriculum significantly
      improved resident confidence in milestone criteria related to population health
      and case-based consultations.

PMID- 26211982
TI  - [A genetic ID for tomorrow?].
AB  - Dozens of private companies have emerged in 2005, with the commercial purpose of
      offering the public a wide variety of personal genetic tests - direct-to-consumer
      personal genome tests. Simultaneously, a collaborative research initiative on
      individual sequencing - the Personal Genome Project - was born in Harvard
      University, then online. This text provides an analysis of the promises and
      limits of the proposed individual sequencing. First, the scope and quality of
      individual predictive genetic sequencing are still far from being acquired.
      Moreover, it is necessary to question the ethical standards of confidentiality
      and respect for privacy in the connected information era.

PMID- 26211983
TI  - Association between Nondominant Unit Total Nucleated Cell Dose and Engraftment in
      Myeloablative Double-Unit Cord Blood Transplantation.
AB  - Sustained hematopoiesis after double-unit cord blood transplantation (dCBT) is
      mediated by 1 unit in nearly all patients. To investigate the associations
      between nondominant unit characteristics and neutrophil engraftment, we studied
      129 consecutive myeloablative dCBT recipients. Ninety-five percent (95%
      confidence interval, 90 to 98) of patients engrafted. Detection of the
      nondominant unit 21 to 28 days after dCBT was not associated with improved
      neutrophil engraftment. In univariate analyses, nondominant unit characteristics
      (infused total nucleated cell [TNC] and viable CD3(+) cell doses) were
      significantly associated with speed and success of neutrophil engraftment as were
      dominant unit characteristics (infused TNC; viable CD34(+), viable CD3(+), and
      viable CD3-56(+)16(+) cell doses; and post-thaw CD34(+) cell viability). In
      multivariate analysis, higher infused TNC dose of the nondominant unit was
      independently associated with improved neutrophil engraftment, even when this
      unit did not contribute to donor hematopoiesis. In further subgroup analysis,
      this association was only evident when the infused viable CD34(+) cell dose of
      the dominant unit was low (<1.20 * 10(5)/kg). These findings suggest nondominant
      units mediate a dose-dependent facilitation of engraftment in myeloablative dCBT
      and support continued investigation of dCBT biology and the clinical practice of
      dCBT in adults in whom low cell dose grafts are common. 

PMID- 26211984
TI  - Reducing Treatment-Related Mortality Did Not Improve Outcomes of Allogeneic
      Myeloablative Hematopoietic Cell Transplantation for High-Risk Multiple Myeloma:
      A University of Michigan Prospective Series.
AB  - Despite the ongoing advent of more effective immunomodulators and proteasome
      inhibitors, multiple myeloma (MM) remains incurable and no effective therapy is
      available for advanced aggressive disease. Although allogeneic (Allo)
      hematopoietic cell transplantation (HCT) has a curative potential, the outcomes
      remain poor because of high treatment-related mortality (TRM), mostly due to
      regimen-related toxicities and graft-versus-host disease (GVHD) in case of
      myeloablative conditionings, high relapse rate in case of reduced-intensity or
      nonmyeloablative regimens, and possibly other unknown MM-specific issues. In an
      attempt to improve TRM, without compromising conditioning intensity, we
      prospectively explored the feasibility and efficacy of a myeloablative but
      reduced-toxicity conditioning regimen, consisting of fludarabine and busulfan
      (FluBu4; fludarabine 40 mg/m(2)/day and busulfan 3.2 mg/kg/day i.v. * 4 days) in
      22 patients with high-risk or advanced refractory MM. The majority (14 of 22,
      64%) had prior autologous HCT. The median HCT-specific comorbidity index score
      was 3 (range, 0 to 6), with 46% having a Karnofsky performance score < 80%. Ten
      patients had unrelated donors, 3 of whom were 7/8 HLA-loci matched. GVHD
      prophylaxis was tacrolimus and methotrexate in 20 (91%). Most patients had active
      MM at transplantation, with a partial response in 12 of 22 (46%) and stable
      disease in 1 of 22 (4.5%). All 22 patients tolerated the FluBu4 conditioning
      well, without early toxic deaths or graft failure. Common regimen-related
      toxicities included mild to moderate mucositis (18 of 22, 82%) and mild transient
      liver function abnormality (9 of 22, 41%). There were no grade 4 toxicities but
      grade 3 mucositis occurred in 7 of 22 patients (32%). The cumulative incidence of
      severe, grades III and IV acute GVHD at day 180 was 23% (95% confidence interval
      [CI], 10% to 47%) and that of chronic GVHD was 68% (95% CI, 46% to 88%). The
      cumulative incidences of TRM at 100 days, 1 year, and 3 years were 9% (95% CI, 2%
      to 33%), 19% (95% CI, 7% to 44%), and 29% (95% CI, 13% to 55%), respectively. Two
      TRMs were due to idiopathic pneumonia syndrome and 1 was due to cirrhosis. They
      all had decreased pre-HCT corresponding organ function, with HCT-specific
      comorbidity index scores of > 3. With a median follow-up of 58.7 (range, 39 to
      82) months, the cumulative incidences of relapse at 1 and 3 years were 37% (95%
      CI, 20% to 61%) and 50% (95% CI, 29% to 75%); those for 1-year and 3-year overall
      survival (OS) were 58% (95% CI, 40% to 83%) and 29% (95% CI, 15% to 57%),
      respectively, and those for the 1-year and 3-year progression-free survivals
      (PFS) were 40% (95% CI, 23% to 67%) and 15% (95% CI, 5% to 42%), respectively. In
      summary, the use of the myeloablative FluBu4 conditioning Allo-HCT for high-risk
      MM resulted in decreased TRM, compared with that of Allo-HCT using conventional
      myeloablative regimens; however, the relapse rate was high, including in those
      developing moderate-to-severe chronic GVHD. This suggested a less robust graft
      versus-myeloma effect against high-risk MM, thus resulting in poor PFS and OS.
      Nonetheless, the FluBu4 regimen may be used as a lower-TRM platform to combine
      with other strategies, eg, addition of an MM-targeted agent and/or maintenance
      therapy with these agents, to decrease relapse or progression in patients with
      high-risk MM. 

PMID- 26211985
TI  - Cytomegalovirus Reactivation after Allogeneic Hematopoietic Stem Cell
      Transplantation is Associated with a Reduced Risk of Relapse in Patients with
      Acute Myeloid Leukemia Who Survived to Day 100 after Transplantation: The Japan
      Society for Hematopoietic Cell Transplantation Transplantation-related
      Complication Working Group.
AB  - Cytomegalovirus (CMV) infection is a major infectious complication after
      allogeneic hematopoietic cell transplantation (allo-HSCT). Recently, it was
      reported that CMV reactivation is associated with a decreased risk of relapse in
      patients with acute myeloid leukemia (AML). The aim of this study was to evaluate
      the impact of early CMV reactivation on the incidence of disease relapse after
      allo-HSCT in a large cohort of patients. The Japan Society for Hematopoietic Cell
      Transplantation's Transplantation-Related Complication Working Group
      retrospectively surveyed the database of the Transplant Registry Unified
      Management Program at the Japan Society for Hematopoietic Cell Transplantation.
      Patients with AML (n = 1836), acute lymphoblastic leukemia (ALL, n = 911),
      chronic myeloid leukemia (CML, n = 223), and myelodysplastic syndrome (MDS, n =
      569) who underwent their first allo-HSCT from HLA-matched related or unrelated
      donors between 2000 and 2009 and who survived without disease relapse until day
      100 after transplantation were analyzed. Patients who received umbilical cord
      blood transplantation were not included. Patients underwent surveillance by pp65
      antigenemia from the time of engraftment, and the beginning of preemptive therapy
      was defined as CMV reactivation. Cox proportional hazards models were used to
      evaluate the risk factors of relapse, nonrelapse, and overall mortality. CMV
      reactivation and acute/chronic graft-versus-host disease (GVHD) were evaluated as
      time-dependent covariates. CMV reactivation was associated with a decreased
      incidence of relapse in patients with AML (20.3% versus 26.4%, P = .027), but not
      in patients with ALL, CML, or MDS. Among 1836 patients with AML, CMV reactivation
      occurred in 795 patients (43.3%) at a median of 42 days, and 436 patients (23.7%)
      relapsed at a median of 221 days after allo-HSCT. Acute GVHD grades II to IV
      developed in 630 patients (34.3%). By multivariate analysis considering competing
      risk factors, 3 factors were significantly associated with a decreased risk of
      AML relapse and 1 factor with an increased risk of AML relapse: CMV reactivation
      (hazard ratio [HR], .77; 95% confidence interval [CI], .59 to .99), unrelated
      donor compared with related donor (HR, .59; 95% CI, .42 to .84), development of
      chronic GVHD (HR, .77; 95% CI, .60 to .99), and pretransplantation advanced
      disease status compared with standard disease status (HR, 1.99; 95% CI, 1.56 to
      2.52). However, CMV reactivation was associated with increased nonrelapse
      mortality (HR, 1.60; 95% CI, 1.18 to 2.17) and overall mortality (HR, 1.37; 95%
      CI, 1.11 to 1.69). A beneficial effect of CMV reactivation on subsequent risk of
      relapse was observed in patients with AML but not in those with other
      hematological malignancies. However, this benefit was nullified by the increased
      nonrelapse mortality. The underlying mechanism is unclear; however, immunological
      activation against CMV reactivation plays an essential role in this association.
      Thus, immune augmentation treatment options, including vaccination and adoptive T
      cell transfer, may be useful to take advantage of the efficacy of CMV
      reactivation with minimal increase in nonrelapse mortality. 

PMID- 26211986
TI  - More than Memory: Potential of Adaptive Natural Killer Cells.

PMID- 26211987
TI  - Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line
      Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin
      Lymphoma.
AB  - This multicenter prospective phase II study examines the activity and
      tolerability of brentuximab vedotin as second-line therapy in patients with
      Hodgkin lymphoma that was relapsed or refractory after induction therapy.
      Brentuximab vedotin (1.8 mg/kg) was administered i.v. on day 1 of a 21-day cycle
      for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell
      transplantation (AHCT), if eligible, with or without additional salvage therapy,
      based on remission status after brentuximab vedotin. The primary endpoint was
      overall response rate (ORR). Secondary endpoints were safety, stem cell
      mobilization/collection, AHCT outcomes, and association of CD68(+) with outcomes.
      Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission).
      The regimen was well tolerated with few grade 3/4 adverse events, including
      lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-two
      patients (86%) were able to proceed to AHCT, with 24 patients (65%) in complete
      remission at time of AHCT. Thirteen patients in complete remission, 4 in partial
      remission, and 1 with stable disease (49%) received AHCT without salvage
      combination chemotherapy. CD68 expression did not correlate with response to
      brentuximab vedotin. The median number of stem cells mobilized was 6.0 * 10(6)
      (range, 2.6 to 34), and median number of days to obtain minimum collection (2 *
      10(6)) was 2 (range, 1 to 6). Brentuximab vedotin as second-line therapy is
      active, well tolerated, and allows adequate stem cell collection and engraftment.
      For Hodgkin lymphoma patients with relapsed/refractory disease after induction
      therapy, second-line brentuximab vedotin, followed by combination chemotherapy
      for residual disease, can effectively bridge patients to AHCT.

PMID- 26211988
TI  - Clostridium Difficile Colonization in Hematopoietic Stem Cell Transplant
      Recipients: A Prospective Study of the Epidemiology and Outcomes Involving
      Toxigenic and Nontoxigenic Strains.
AB  - Clostridium difficile is a leading cause of infectious diarrhea in hematopoietic
      stem cell transplant (HSCT) recipients. Asymptomatic colonization of the
      gastrointestinal tract occurs before development of C. difficile infection (CDI).
      This prospective study examines the rates, risk factors, and outcomes of
      colonization with toxigenic and nontoxigenic strains of C. difficile in HSCT
      patients. This 18-month study was conducted in the HSCT unit at the Karmanos
      Cancer Center and Wayne State University in Detroit. Stool samples from the
      patients who consented for the study were taken at admission and weekly until
      discharge. Anaerobic culture for C. difficile and identification of toxigenic
      strains by PCR were performed on the stool samples. Demographic information and
      clinical and laboratory data were collected. Of the 150 patients included in the
      study, 29% were colonized with C. difficile at admission; 12% with a toxigenic
      strain and 17% with a nontoxigenic strain. Over a 90-day follow-up, 12 of 44
      (26%) patients colonized with any C. difficile strain at admission developed CDI
      compared with 13 of 106 (12%) of patients not colonized (odds ratio [OR], 2.70;
      95% confidence interval [95% CI], 1.11 to 6.48; P = .025). Eleven of 18 (61%)
      patients colonized with the toxigenic strain and 1 of 26 (4%) of those colonized
      with nontoxigenic strain developed CDI (OR, 39.30; 95% CI, 4.30 to 359.0; P <
      .001) at a median of 12 days. On univariate and multivariate analyses, none of
      the traditional factors associated with high risk for C. difficile colonization
      or CDI were found to be significant. Recurrent CDI occurred in 28% of cases.
      Asymptomatic colonization with C. difficile at admission was high in our HSCT
      population. Colonization with toxigenic C. difficile was predictive of CDI,
      whereas colonization with a nontoxigenic C. difficile appeared protective. These
      findings may have implications for infection control strategies and for novel
      approaches for the prevention and preemptive treatment of CDI in the HSCT patient
      population.

PMID- 26211990
TI  - Orthopedic complications in diabetes.
AB  - Diabetes is associated with a number of lower extremity orthopedic conditions and
      complications including fractures, Charcot neuroarthropathy, plantar ulcers, and
      infection. These complications are of significant clinical concern in terms of
      morbidity, mortality, and socioeconomic costs. A review of each condition is
      discussed, with particular emphasis on the clinical importance, diagnostic
      considerations, and orthopedic treatment recommendations. The goal of the article
      is to provide a clinical picture of the challenges that orthopedic surgeons
      confront, and highlight the need for specific clinical guidelines in diabetic
      patients. 

PMID- 26211989
TI  - Determinants of bone strength and quality in diabetes mellitus in humans.
AB  - There is growing evidence that the higher fracture rate observed in patients with
      type 2 diabetes mellitus (T2DM) is associated with normal, or even increased,
      areal bone mineral density (aBMD) by DXA. This has led to the hypothesis that
      patients with T2DM may have abnormalities in bone microarchitecture and/or
      material composition - i.e., key determinants of bone "quality." Consistent with
      this hypothesis, several studies using high-resolution peripheral quantitative
      computed tomography (HRpQCT) have demonstrated preserved indices of trabecular
      microarchitecture but increased cortical porosity in T2DM patients. In addition,
      a recent study using a novel in vivo microindentation device found an impairment
      in a measure of bone material properties (bone material strength index, BMSi) in
      postmenopausal women with longstanding T2DM; notably, the reduction in BMSi was
      associated with chronic glycemic control, suggesting that the skeleton should be
      included as another target organ subject to diabetic complications. The
      underlying pathogenesis of skeletal fragility in T2DM remains to be defined,
      although high levels of advanced glycation endproducts (AGEs) may play a role. In
      addition, T2DM is associated with reduced bone turnover, perhaps with an
      imbalance between bone resorption and bone formation. Although several studies
      have found increased serum sclerostin levels in patients with T2DM, the role of
      these increased levels in mediating the observed increases in cortical porosity
      or reduction in BMSi remains to be defined. Thus, although bone quality appears
      to be impaired in T2DM, the pathogenesis of these abnormalities and their
      relationship to the increased fracture risk observed in these patients needs
      further study. 

PMID- 26211991
TI  - Membrane depolarization regulates intracellular RANKL transport in non-excitable
      osteoblasts.
AB  - Parathyroid hormone (PTH) and 1alpha,25-dihydroxyvitamin D3 (VD3) are important
      factors in Ca(2+) homeostasis, and promote osteoclastogenesis by modulating
      receptor activator of nuclear factor kappa-B ligand (RANKL) mRNA expression.
      However, their contribution to RANKL intracellular transport (RANKLiT), including
      the trigger for RANKL lysosomal vesicle (RANKL-lv) fusion to the cell membrane,
      is unclear. In neurons, depolarization of membrane potential increases the
      intracellular Ca(2+) level ([Ca(2+)]i) and promotes neurotransmitter release via
      fusion of the synaptic vesicles to the cell membrane. To determine whether
      membrane depolarization also regulates cellular processes such as RANKLiT in
      MC3T3-E1 osteoblasts (OBs), we generated a light-sensitive OB cell line and
      developed a system for altering their membrane potential via delivery of a blue
      light stimulus. In the membrane fraction of RANKL-overexpressing OBs, PTH and VD3
      increased the membrane-bound RANKL (mbRANKL) level at 10 min after application
      without affecting the mRNA expression level, and depolarized the cell membrane
      while transiently increasing [Ca(2+)]i. In our novel OB line stably expressing
      the channelrhodopsin-wide receiver, blue light-induced depolarization increased
      the mbRANKL level, which was reversed by treatment of blockers for L-type voltage
      gated Ca(2+) channels and Ca(2+) release from the endoplasmic reticulum. In co
      cultures of osteoclast precursor-like RAW264.7 cells and light-sensitive OBs
      overexpressing RANKL, light stimulation induced an increase in tartrate-resistant
      acid phosphatase activity and promoted osteoclast differentiation. These results
      indicate that depolarization of the cell membrane is a trigger for RANKL-lv
      fusion to the membrane and that membrane potential contributes to the function of
      OBs. In addition, the non-genomic action of VD3-induced RANKL-lv fusion included
      the membrane-bound VD3 receptor (1,25D3-MARRS receptor). Elucidating the
      mechanism of RANKLiT regulation by PTH and VD3 will be useful for the development
      of drugs to prevent bone loss in osteoporosis and other bone diseases.

PMID- 26211992
TI  - Raman spectral classification of mineral- and collagen-bound water's associations
      to elastic and post-yield mechanical properties of cortical bone.
AB  - Water that is bound to bone's matrix is implied as a predictor of fracture
      resistance; however, bound water is an elusive variable to be measured
      nondestructively. To date, the only nondestructive method used for studying bone
      hydration status is magnetic resonance variants (NMR or MRI). For the first time,
      bone hydration status was studied by short-wave infrared (SWIR) Raman
      spectroscopy to investigate associations of mineral-bound and collagen-bound
      water compartments with mechanical properties. Thirty cortical bone samples were
      used for quantitative Raman-based water analysis, gravimetric analysis, porosity
      measurement, and biomechanical testing. A sequential dehydration protocol was
      developed to replace unbound (heat drying) and bound (ethanol treatment) water in
      bone. Raman spectra were collected serially to track the OH-stretch band during
      dehydration. Four previously identified peaks were investigated: I3220/I2949,
      I3325/I2949 and I3453/I2949 reflect status of organic-matrix related water
      (mostly collagen-related water) compartments and collagen portion of bone while
      I3584/I2949 reflects status of mineral-related water compartments and mineral
      portion of bone. These spectroscopic biomarkers were correlated with elastic and
      post-yield mechanical properties of bone. Collagen-water related biomarkers
      (I3220/I2949 and I3325/I2949) correlated significantly and positively with
      toughness (R(2)=0.81 and R(2)=0.79; p<0.001) and post-yield toughness (R(2)=0.65
      and R(2)=0.73; p<0.001). Mineral-water related biomarker correlated significantly
      and negatively with elastic modulus (R(2)=0.78; p<0.001) and positively with
      strength (R(2)=0.46; p<0.001). While MR-based techniques have been useful in
      measuring unbound and bound water, this is the first study which probed bound
      water compartments differentially for collagen and mineral-bound water. For the
      first time, we showed an evidence for contributions of different bound-water
      compartments to mechanical properties of wet bone and the reported correlations
      of Raman-based water measurements to mechanical properties underline the
      necessity for enabling approaches to assess these new biomarkers noninvasively in
      vivo to improve the current diagnosis of those who may be at risk of bone
      fracture due to aging and diseases. 

PMID- 26211993
TI  - Effect of type 2 diabetes-related non-enzymatic glycation on bone biomechanical
      properties.
AB  - There is clear evidence that patients with type 2 diabetes mellitus (T2D) have
      increased fracture risk, despite having high bone mineral density (BMD) and body
      mass index (BMI). Thus, poor bone quality has been implicated as a mechanism
      contributing to diabetic skeletal fragility. Poor bone quality in T2D may result
      from the accumulation of advanced glycation end-products (AGEs), which are post
      translational modifications of collagen resulting from a spontaneous reaction
      between extracellular sugars and amino acid residues on collagen fibers. This
      review discusses what is known and what is not known regarding AGE accumulation
      and diabetic skeletal fragility, examining evidence from in vitro experiments to
      simulate a diabetic state, ex vivo studies in normal and diabetic human bone, and
      diabetic animal models. Key findings in the literature are that AGEs increase
      with age, affect bone cell behavior, and are altered with changes in bone
      turnover. Further, they affect bone mechanical properties and microdamage
      accumulation, and can be inhibited in vitro by various inhibitors and breakers
      (e.g. aminoguanidine, N-Phenacylthiazolium Bromide, vitamin B6). While a few
      studies report higher AGEs in diabetic animal models, there is little evidence of
      AGE accumulation in bone from diabetic patients. There are several limitations
      and inconsistencies in the literature that should be noted and studied in greater
      depth including understanding the discrepancies between glycation levels across
      reported studies, clarifying differences in AGEs in cortical versus cancellous
      bone, and improving the very limited data available regarding glycation content
      in diabetic animal and human bone, and its corresponding effect on bone material
      properties in T2D. 

PMID- 26211994
TI  - Skeletal integration of energy homeostasis: Translational implications.
AB  - New evidence has recently emerged defining a close relationship between fat and
      bone metabolism. Adipose tissue is one of the largest organs in the body but its
      functions vary by location and origin. Adipocytes can act in an autocrine manner
      to regulate energy balance by sequestering triglycerides and then, depending on
      demand, releasing fatty acids through lipolysis for energy utilization, and in
      some cases through uncoupling protein 1 for generating heat. Adipose tissue can
      also act in an endocrine or paracrine manner by releasing adipokines that
      modulate the function of other organs. Bone is one of those target tissues,
      although recent evidence has emerged that the skeleton reciprocates by releasing
      its own factors that modulate adipose tissue and beta cells in the pancreas.
      Therefore, it is not surprising that these energy-modulating tissues are
      controlled by a central regulatory mechanism, primarily the sympathetic nervous
      system. Disruption in this complex regulatory circuit and its downstream tissues
      is manifested in a wide range of metabolic disorders, for which the most
      prevalent is type 2 diabetes mellitus. The aim of this review is to summarize our
      knowledge of common determinants in the bone and adipose function and the
      translational implications of recent work in this emerging field. 

PMID- 26211995
TI  - Exercise increases pyridinoline cross-linking and counters the mechanical effects
      of concurrent lathyrogenic treatment.
AB  - The collagen cross-link profile of bone, associated with bone strength and
      fracture toughness, is tightly regulated (affecting cross-link quantity, type,
      lysine hydroxylation and maturity) and may contribute to the improvements in bone
      quality during exercise. We hypothesized that 1) exercise promotes mature cross
      link formation, 2) increased mature cross-linking is accompanied by shifts in
      lysine hydroxylation, and 3) these changes in collagen cross-link profile have
      positive effects on mechanical properties. Growing male C57Bl6 mice were treated
      with 30 min/day of running exercise, 350 mg/kg/day beta-aminopropionitrile (BAPN)
      injected subcutaneously to inhibit enzymatic collagen cross-linking, or both
      exercise and BAPN, from 5 to 8 weeks of age. Bone collagen cross-linking profile,
      mechanical properties, morphology, and mineralization were measured from the
      tibiae. Cross-link measures, including immature, pyridinoline, pyrrole and
      pentosidine cross-links, ratios reflecting cross-link maturity and hydroxylation,
      and mineralization were tested for their importance to mechanical properties
      across 8 week groups through correlation analyses and step-wise linear
      regressions. BAPN treatment significantly reduced lysylpyridinoline, pyrrole,
      hydroxylysinorleucine, and total mature collagen cross-linking, resulting in
      decreased bone elastic modulus and increased yield strain despite a marginal
      increase in TMD. Exercise caused a shift toward pyridinoline cross-linking, with
      increased hydroxylysylpyridinoline and decreased pyrrole cross-linking resulting
      in total mature cross-linking and estimated tissue level mechanical properties
      matching sedentary control levels. Exercise superimposed on BAPN treatment
      increased total mature cross-linking from BAPN to control levels, but did so by
      increasing pyridinoline, not pyrrole, cross-links. Exercise also counteracted the
      BAPN effects on modulus and strain, without a change in TMD. Pyrrole cross
      linking was the strongest correlate of modulus (r=0.470, p<0.01) and yield strain
      (r=-0.467, p<0.01). Cross-links with similar levels of telopeptide lysine
      hydroxylation to pyrrole (lysylpyridinoline and hydroxylysinorleucine) also
      correlated with modulus and strain to a lesser extent. In conclusion, exercise in
      growing mice promotes pyridinoline collagen cross-linking in bone, the resulting
      increase in total mature cross-linking is sufficient to counteract the mechanical
      effects of concurrent cross-link inhibition, and this responsiveness to loading
      is a potential means by which exercise might improve bone quality in diseased or
      otherwise compromised bone.

PMID- 26211997
TI  - Associations of daily pediatric asthma emergency department visits with air
      pollution in Newark, NJ: utilizing time-series and case-crossover study designs.
AB  - OBJECTIVE: Asthma is one of the most common chronic diseases affecting children.
      This study assesses the associations of ozone and fine particulate matter (PM2.5)
      with pediatric emergency department visits in the urban environment of Newark,
      NJ. Two study designs were utilized and evaluated for usability. METHODS: We
      obtained daily emergency department visits among children aged 3-17 years with a
      primary diagnosis of asthma during April to September for 2004-2007. Both a time
      stratified case-crossover study design with bi-directional control sampling and a
      time-series study design were utilized. Lagged effects (1-d through 5-d lag, 3-d
      average, and 5-d average) of ozone and PM2.5 were explored and a dose-response
      analysis comparing the bottom 5th percentile of 3-d average lag ozone with each 5
      percentile increase was performed. RESULTS: Associations of interquartile range
      increase in same-day ozone were similar between the time-series and case
      crossover study designs (RR = 1.08, 95% CI 1.04-1.12) and (OR = 1.10, 95% CI 1.06
      1.14), respectively. Similar associations were seen for 1-day lag and 3-day
      average lag ozone levels. PM2.5 was not associated with the outcome in either
      study design. Dose-response assessment indicated a statistically significant and
      increasing association around 50-55 ppb consistent for both study designs.
      CONCLUSIONS: Ozone was statistically positively associated with pediatric asthma
      ED visits in Newark, NJ. Our results were generally comparable across the time
      series and case-crossover study designs, indicating both are useful to assess
      local air pollution impacts.

PMID- 26211996
TI  - SGLT2 inhibitor therapy improves blood glucose but does not prevent diabetic bone
      disease in diabetic DBA/2J male mice.
AB  - Persons with type 1 and type 2 diabetes have increased fracture risk, attributed
      to deficits in the microarchitecture and strength of diabetic bone, thought to be
      mediated, in part, by the consequences of chronic hyperglycemia. Therefore, to
      examine the effects of a glucose-lowering SGLT2 inhibitor on blood glucose (BG)
      and bone homeostasis in a model of diabetic bone disease, male DBA/2J mice with
      or without streptozotocin (STZ)-induced hyperglycemia were fed chow containing
      the SGLT2 inhibitor, canagliflozin (CANA), or chow without drug, for 10weeks of
      therapy. Thereafter, serum bone biomarkers were measured, fracture resistance of
      cortical bone was assessed by MUCT analysis and a three-point bending test of the
      femur, and vertebral bone strength was determined by compression testing. In the
      femur metaphysis and L6 vertebra, long-term diabetes (DM) induced deficits in
      trabecular bone microarchitecture. In the femur diaphysis, a decrease in cortical
      bone area, cortical thickness and minimal moment of inertia occurred in DM
      (p<0.0001, for all) while cortical porosity was increased (p<0.0001). These DM
      changes were associated with reduced fracture resistance (decreased material
      strength and toughness; decreased structural strength and rigidity; p<0.001 for
      all). Significant increases in PTH (p<0.0001), RatLAPs (p=0.0002), and urine
      calcium concentration (p<0.0001) were also seen in DM. Canagliflozin treatment
      improved BG in DM mice by ~35%, but did not improve microarchitectural
      parameters. Instead, in canagliflozin-treated diabetic mice, a further increase
      in RatLAPs was evident, possibly suggesting a drug-related intensification of
      bone resorption. Additionally, detrimental metaphyseal changes were noted in
      canagliflozin-treated control mice. Hence, diabetic bone disease was not
      favorably affected by canagliflozin treatment, perhaps due to insufficient
      glycemic improvement. Instead, in control mice, long-term exposure to SGLT2
      inhibition was associated with adverse effects on the trabecular compartment of
      bone. 

PMID- 26211998
TI  - Crystal Orientation Dynamics of Collective Zn dots before Preferential
      Nucleation.
AB  - The island nucleation in the context of heterogeneous thin film growth is often
      complicated by the growth kinetics involved in the subsequent thermodynamics. We
      show how the evolution of sputtered Zn island nucleation on Si(111) by magnetron
      sputtering in a large area can be completely understood as a model system by
      combining reflective second harmonic generation (RSHG), a 2D pole figure with
      synchrotron X-ray diffraction. Zn dots are then oxidized on the surfaces when
      exposed to the atmosphere as Zn/ZnO dots. Derived from the RSHG patterns of Zn
      dots at different growth times, the Zn dots grow following a unique transition
      from kinetic to thermodynamic control. Under kinetic-favoring growth, tiny Zn
      dots prefer arranging themselves with a tilted c-axis to the Si(111) substrate
      toward any of the sixfold in-plane Si<110> directions. Upon growth, the Zn dots
      subsequently evolve themselves to a metastable state with a smaller tilting angle
      toward selective <110> directions. As the Zn dots grow over a critical size, they
      become most thermodynamically stable with the c-axis vertical to the Si(111)
      substrate. For a system with large lattice mismatch, small volume dots take
      kinetic pathways with insignificant deviations in energy barriers. 

PMID- 26211999
TI  - Degradation of (La(0.8)Sr(0.2))(0.98)MnO(3-delta)-Zr(0.84)Y(0.16)O(2-gamma)
      composite electrodes during reversing current operation.
AB  - Reversing-current operation of solid oxide cell (La(0.8)Sr(0.2))(0.98)MnO(3
      delta)-Zr(0.84)Y(0.16)O(2-gamma) (LSM-YSZ) oxygen electrodes is described.
      Degradation was characterized by impedance spectroscopy in symmetric cells tested
      at 800  degrees C in air with a symmetric current cycle with a period of 12
      hours. No change in cell resistance could be detected, in 1000 h tests with a
      sensitivity of ~1% per kh, at a current density of 0.5 A cm(-2) corresponding to
      an overpotential of 0.18 V. At a current density to 0.6 A cm(-2) (0.33 V
      overpotential) measurable resistance degradation at a rate of 3% per kh was
      observed, while higher current/overpotential values led to faster degradation.
      Degradation was observed mainly in the ohmic resistance for current densities of
      0.6, 0.8 and 0.9 A cm(-2), with little change in the polarization resistance.
      Polarization degradation, mainly observed at higher current density, was present
      as an increase in an impedance response at ~30 kHz, apparently associated with
      the resistance of YSZ grain boundaries within the electrode. Microstructural and
      chemical analysis showed significant changes in electrode structure after the
      current cycling, including an increase in LSM particle size and a reduction in
      the amount of YSZ and LSM at the electrode/electrolyte interface - the latter
      presumably a precursor to delamination.

PMID- 26212000
TI  - Identification of immunotherapeutic epitope of E5 protein of human papillomavirus
      16: An in silico approach.
AB  - Cervical cancer is one of the most common gynaecological cancer in India and
      contributes 1/3rd of global burden. High risk-human papillomavirus (HR-HPV) is
      the major etiological factor for development of cervical cancer. Two available
      HPV vaccines provide protection against HPV induced cervical malignancy. However,
      vaccines having therapeutic values are of utmost priority. Till date, most of HPV
      therapeutic vaccines are focused on two major HPV oncoproteins (E6/E7). HPV-E5
      which acts by altering the activity of cellular proteins, mainly growth factor
      pathways emerges as a new therapeutic target. In present study, we predicted the
      candidate B-cell and T-cell epitopes of HPV16-E5, which can be used for HPV
      immunotherapy. We identified that epitope SAFRCFIVYIIFVY as most potent peptide
      for HLA-A*11:01 having percentile value of 0.5 and immunogenicity score of
      0.69558. For MHC-II, epitopes IPLFLIHTHARFLIT for HLA-DRB1*14:01 alleles have the
      lowest IC50 value (18.13 nM). The identification of structural feature and
      immunogenic epitopes provides the best information for development of drugs or
      vaccine. In conclusion, the expression of E5 protein was detected in the early
      phase of the HPV infection, which gives an opportunity to target HPV-E5 that
      would help in the prevention and progression of the precancerous lesion to
      invasive carcinomas. 

PMID- 26212001
TI  - Two new sesquiterpene lactones from the fruits of Illicium jiadifengpi.
AB  - Two new seco-prezizaane-type sesquiterpenes, 3,4-dehydroneomajucin (1) and
      1,2,3,4-tetradehydroneomajucin (2), were isolated from the fruits of Illicium
      jiadifengpi. The structure of these compounds was determined using 1D and 2D NMR
      and ESI-MS. The isolates were evaluated for their anti-hepatitis B virus
      activities on the Hep G2.2.15 cell line. The inhibitory rates of compounds 1 and
      2 on the HBeAg and HBsAg expression were 30.08 +/- 3.09% and 11.43 +/- 1.92% at a
      concentrations of 68.00 MUM and 7.88 +/- 1.21% and 16.96 +/- 4.24% at a
      concentration of 68.50 MUM, respectively.

PMID- 26212002
TI  - Soft tissue histomorphology at implants with a transmucosal modified surface. A
      study in minipigs.
AB  - OBJECTIVES: To investigate soft tissue histomorphology and quality around
      implants with a modified transgingival collar surface comparatively to a
      machined. MATERIAL AND METHODS: Twenty-seven Straumann Standard Tissue Level
      implants belonging to the following groups (nine of each group): Ti modSLA with
      machined collar (Ti-M), Ti modSLA with machined, acid-etched surface collar (Ti
      modMA), and TiZr modSLA with machined, acid-etched surface collar (TiZr-modMA)
      were placed in the mandible of six minipigs. After 8 weeks of healing, buccal
      sections were obtained and processed for histological evaluation. RESULTS:
      Histometric soft tissue outcomes were similar for the three types of implants.
      The percentage of connective tissue attached to implant surface and its length
      was longer at TiZr-modMA with respect to Ti-M implants. The number of
      inflammatory cells was slightly higher at the TiZr-modMA with respect to Ti-M
      implant. The percentage of area occupied by perpendicular collagen fibers was
      slightly higher for the modified surfaces in comparison with the machined.
      CONCLUSIONS: Modified implant collar surfaces at Ti and TiZr implants showed a
      soft tissue interface similar to machined. A tendency of increasing number of
      perpendicular collagen fibers and improved connective tissue contact was found at
      the modified implant surfaces.

PMID- 26212003
TI  - Hepatitis E vaccine immunization for rabbits to prevent animal HEV infection and
      zoonotic transmission.
AB  - Hepatitis E virus (HEV) infection has become a significant global public health
      concern as increasing cases of acute and chronic hepatitis E are reported. HEV of
      animal origin was proved to be a possible source of human infection and a
      previous study showed that the recent licensed HEV 239 vaccine can serve as a
      candidate vaccine to manage animal sources of HEV infection. However, previous
      immunization strategy for rabbits was the same as that for human, which is too
      costly to conduct large-scale animal vaccination. In an effort to reduce the
      costs, three vaccination schemes were assessed in the present study. Forty
      specific pathogen-free (SPF) rabbits were divided randomly into five groups with
      eight animals for each and inoculated intramuscularly with different doses of HEV
      239 and placebo, respectively. All animals were challenged intravenously with
      swine HEV-4 and rabbit HEV of different titers 7 weeks after the initial
      immunization and then fecal virus excretion was monitored for 10 weeks. The
      results indicated that immunizing rabbits with two 10MUg doses of the vaccine is
      superior to vaccination with two 20MUg doses or a single 30MUg dose, which can
      protect rabbits against homologous and heterologous HEV infection. These findings
      could enable implementation of large-scale animal vaccination to prevent rabbit
      HEV infection and zoonotic transmission. 

PMID- 26212004
TI  - Management of Bacillus Calmette-Guerin osteomyelitis/osteitis in immunocompetent
      children-A systematic review.
AB  - BACKGROUND: Bacillus Calmette-Guerin (BCG) osteomyelitis/osteitis in
      immunocompetent children is a rare but serious complication of BCG immunization.
      Rationale for its treatment is unclear. METHODS: Due to the rarity of this
      complication, no randomized control trials has ever been conducted to evaluate
      methods of intervention. As such, we searched the literature for any reported BCG
      vaccination-related osteomyelitis/osteitis among immunecompetent children
      published before April 15, 2014. We summarized the data from different affected
      regions of the body by recording the number of reported cases, while noting
      outcomes and their medical and/or surgical interventions. RESULTS: From 34
      eligible studies gleaned from a screening of 804 articles, a total of 331 cases
      were enrolled. Involvement of the lower limbs was present in 55.6%, followed by
      the axial skeleton (26.0%), the upper limbs (15.4%), and multiple bones (3.0%).
      Of the 64 patients having records of detailed chemotherapy regimens, 45 patients
      (70%) received two or fewer drugs. Among the 80 patients with detailed surgical
      records, 50 (62.5%) received surgical procedures for diagnostic purposes. While
      there were uneventful outcomes for those receiving diagnostic procedures, 7 of
      the 30 (23.3%) patients receiving surgical interventions had major complications
      (p=0.002, Fisher's exact test). The overall prognosis was good with a 97.6% cure
      rate. Nevertheless, eight patients (2.4%) suffered major complications.
      CONCLUSIONS: The rationale for treatment of BCG osteomyelitis/osteitis in
      immunocompetent children is highly subjective. However, patients receiving
      diagnostic procedures instead of surgical interventions may avoid major
      complications. Because only a few of the publications had detailed treatment
      information, further studies are needed to identify proper treatments, while
      infant BCG vaccination is still in use.

PMID- 26212005
TI  - Foot-and-mouth disease virus infection of dendritic cells triggers
      phosphorylation of ERK1/2 inducing class I presentation and apoptosis.
AB  - Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven
      hoofed animals. This pathology is caused by foot-and-mouth disease virus (FMDV).
      Over time, the development of vaccines to prevent the spread of this illness
      became essential. Vaccines currently used contain the inactivated form of the
      virus. However, vaccination generates an immune response different to that
      induced by the infection. We investigated whether these differences are related
      to intracellular mechanisms on dendritic cells (DCs). As a result, we
      demonstrated that the internalization of infective virus triggered the
      phosphorylation of ERK1/2, which was involved in the activation of caspase-9, the
      intrinsic pathway of apoptosis and the delivery of viral peptides on MHC class I
      molecules. While, inactivated virus (iFMDV) did not affect this pathway or any
      function mediated by its activation. As described, infectious virus in DCs was
      also associated to autophagy LC3 protein and was associated to lysosomal protein
      Lamp-2; contrary to observe for the iFMDV. Strikingly, the processing of viral
      antigens to accommodate in class I molecules does not appear to involve the
      proteasome. Finally, this increased presentation promotes a specific cytotoxic
      response against infectious virus. 

PMID- 26212006
TI  - PHiD-CV induces anti-Protein D antibodies but does not augment pulmonary
      clearance of nontypeable Haemophilus influenzae in mice.
AB  - BACKGROUND: A recently-licensed 10-valent pneumococcal conjugate vaccine (PHiD
      CV; Synflorix, GSK) uses Protein D from Haemophilus influenzae as a carrier
      protein. PHiD-CV therefore has the potential to provide additional protection
      against nontypeable H. influenzae (NTHi). NTHi frequently causes respiratory
      tract infections and is associated with significant morbidity and mortality
      worldwide and there is currently no vaccine. METHODS: We developed mouse models
      of NTHi infection and influenza/NTHi superinfection. Mice were immunized with
      PHiD-CV, heat-killed NTHi, or a 13-valent pneumococcal conjugate vaccine that did
      not contain Protein D (PCV13; Prevenar, Pfizer) and then infected intranasally
      with NTHi. RESULTS: Infection with NTHi resulted in weight loss, inflammation and
      airway neutrophilia. In a superinfection model, prior infection with pandemic
      H1N1 influenza virus (strain A/England/195/2009) augmented NTHi infection
      severity, even with a lower bacterial challenge dose. Immunization with PHiD-CV
      produced high levels of antibodies that were specific against Protein D, but not
      heat-killed NTHi. Immunization with PHiD-CV led to a slight reduction in
      bacterial load, but no change in disease outcome. CONCLUSIONS: PHiD-CV induced
      high levels of Protein D-specific antibodies, but did not augment pulmonary
      clearance of NTHi. We found no evidence to suggest that PHiD-CV will offer added
      benefit by preventing NTHi lung infection.

PMID- 26212007
TI  - Prevention of serious events in adults 65 years of age or older: A comparison
      between high-dose and standard-dose inactivated influenza vaccines.
AB  - BACKGROUND: A recent study showed that a high-dose inactivated influenza vaccine
      (IIV-HD) was 24.2% more efficacious than a standard-dose inactivated influenza
      vaccine (IIV-SD) in preventing laboratory-confirmed symptomatic influenza in
      adults >=65 years. Here we evaluate the effectiveness of IIV-HD compared to IIV
      SD in preventing serious illnesses considered potential sequelae or complications
      of influenza infection. METHODS: The original study was a double-blind,
      randomized, active-controlled, multicenter trial. Participants were adults >=65
      years randomized to receive IIV-HD or IIV-SD, and followed for 6-8 months post
      vaccination for the occurrence of influenza and serious adverse events (SAEs).
      SAEs were events: leading to death or hospitalization (or its prolongation);
      considered life-threatening or medically important; or resulting in disability.
      For the present analysis, reported SAEs were classified as possibly related to
      influenza by three blinded physicians and rates per 1000 participant-seasons were
      calculated. Relative vaccine effectiveness (rVE) was estimated as (1-Rate
      Ratio)*100. RESULTS: 31,989 participants were enrolled, with 15,991 and 15,998
      randomized to receive IIV-HD and IIV-SD, respectively. IIV-HD was significantly
      more effective than IIV-SD in preventing SAEs possibly related to influenza
      overall (rVE, 17.7%; 95% confidence interval [CI], 6.6-27.4%) and serious
      pneumonia (rVE, 39.8%; 95% CI, 19.3-55.1%). Borderline significance was observed
      for the efficacy of IIV-HD relative to IIV-SD for the prevention of all-cause
      hospitalizations (rVE, 6.9%; 95% CI, 0.5-12.8%). CONCLUSIONS: Compared to IIV-SD,
      IIV-HD reduced the risk of SAEs possibly related to influenza. The observed
      relative effectiveness against serious pneumonia is particularly noteworthy
      considering the burden of influenza and pneumonia in older adults.

PMID- 26212008
TI  - CXCR7 mediates TGFbeta1-promoted EMT and tumor-initiating features in lung
      cancer.
AB  - In the tumor microenvironment, chemokine system has a critical role in
      tumorigenesis and metastasis. The acquisition of stem-like properties by cancer
      cells is involved in metastasis and drug resistance, which are pivotal problems
      that result in poor outcomes in patients with lung cancer. Patients with advanced
      lung cancer present high plasma levels of transforming growth factor-beta1
      (TGFbeta1), which correlate with poor prognostic features. Therefore, TGFbeta1
      may be important in the tumor microenvironment, where chemokines are widely
      expressed. However, the role of chemokines in TGFbeta1-induced tumor progression
      still remains unclear. In our study, TGFbeta1 upregulated CXC chemokine receptor
      expression, migration, invasion, epithelial-mesenchymal transition (EMT) and
      cancer stem cell (CSC) formation in lung adenocarcinoma. We found that CXCR7 was
      the most upregulated chemokine receptor induced by TGFbeta1. CXCR7 knockdown
      resulted in reduction of migration, invasion and EMT induced by TGFbeta1, whereas
      CXCR4 knockdown did not reverse TGFbeta1-promoted EMT. CXCR7 silencing
      significantly decreased cancer sphere-forming capacity, stem-like properties,
      chemoresistance and TGFbeta1-induced CSC tumor initiation in vivo. In clinical
      samples, high TGFbeta1 and CXCR7 expression was significantly associated with the
      late stages of lung adenocarcinoma. Moreover, TGFbeta1 and CXCR7 coexpression was
      positively correlated with the CSC marker, CD44, which is associated with lymph
      node metastasis. Besides, patients with high expression of both CXCR7 and
      TGFbeta1 presented a significantly worse survival rate. These results suggest
      that the TGFbeta1-CXCR7 axis may be a prognostic marker and may provide novel
      targets for combinational therapies to be used in the treatment of advanced lung
      cancer in the future.

PMID- 26212009
TI  - PAK5-mediated E47 phosphorylation promotes epithelial-mesenchymal transition and
      metastasis of colon cancer.
AB  - The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the
      transcription factor E47 is a direct repressor of E-cadherin and inducer of
      epithelial-mesenchymal transition (EMT). However, the relationship between PAK5
      and E47 has not been explored. In this study, we found that PAK5-mediated E47
      phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47
      and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation,
      which decreased cell-cell cohesion, increased cell migration and invasion in
      vitro and promoted metastasis in a xenograft model. Furthermore, phosphorylation
      of E47 facilitated its accumulating in nucleus in an importin alpha-dependent
      manner, and enhanced E47 binding to E-cadherin promoter directly, leading to
      inhibition of E-cadherin transcription. In contrast, PAK5-knockdown resulted in
      blockage of HGF-induced E47 phosphorylation, attenuated association of E47 with
      importin alpha and decreased E47 binding to E-cadherin promoter. In addition, we
      demonstrated a close correlation between PAK5 and phospho-Ser39 E47 expression in
      colon cancer specimens. More importantly, high expression of phospho-E47 was
      associated with an aggressive phenotype of colon cancer and nuclear phospho-E47
      staining was found in certain cases of colon cancer with metastasis.
      Collectively, E47 is a novel substrate of PAK5, and PAK5-mediated phosphorylation
      of E47 promotes EMT and metastasis of colon cancer, suggesting that
      phosphorylated E47 on Ser39 may be a potential therapeutic target in progressive
      colon cancer. 

PMID- 26212010
TI  - Stat3 regulates ErbB-2 expression and co-opts ErbB-2 nuclear function to induce
      miR-21 expression, PDCD4 downregulation and breast cancer metastasis.
AB  - Membrane overexpression of the receptor tyrosine kinase ErbB-2 (MErbB-2) accounts
      for a clinically aggressive breast cancer (BC) subtype (ErbB-2-positive) with
      increased incidence of metastases. We and others demonstrated that nuclear ErbB-2
      (NErbB-2) also plays a key role in BC and is a poor prognostic factor in ErbB-2
      positive tumors. The signal transducer and activator of transcription 3 (Stat3),
      another player in BC, has been recognized as a downstream mediator of MErbB-2
      action in BC metastasis. Here, we revealed an unanticipated novel direction of
      the ErbB-2 and Stat3 interaction underlying BC metastasis. We found that Stat3
      binds to its response elements (GAS) at the ErbB-2 promoter to upregulate ErbB-2
      transcription in metastatic, ErbB-2-positive BC. We validated these results in
      several BC subtypes displaying metastatic and non-metastatic ability,
      highlighting Stat3 general role as upstream regulator of ErbB-2 expression in BC.
      Moreover, we showed that Stat3 co-opts NErbB-2 function by recruiting ErbB-2 as
      its coactivator at the GAS sites in the promoter of microRNA-21 (miR-21), a
      metastasis-promoting microRNA (miRNA). Using an ErbB-2 nuclear localization
      domain mutant and a constitutively activated ErbB-2 variant, we found that NErbB
      2 role as a Stat3 coactivator and also its direct role as transcription factor
      upregulate miR-21 in BC. This reveals a novel function of NErbB-2 as a regulator
      of miRNAs expression. Increased levels of miR-21, in turn, downregulate the
      expression of the metastasis-suppressor protein programmed cell death 4 (PDCD4),
      a validated miR-21 target. Using an in vivo model of metastatic ErbB-2-postive
      BC, in which we silenced Stat3 and reconstituted ErbB-2 or miR-21 expression, we
      showed that both are downstream mediators of Stat3-driven metastasis. Supporting
      the clinical relevance of our results, we found an inverse correlation between
      ErbB-2/Stat3 nuclear co-expression and PDCD4 expression in ErbB-2-positive
      primary invasive BCs. Our findings identify Stat3 and NErbB-2 as novel
      therapeutic targets to inhibit ErbB-2-positive BC metastasis.

PMID- 26212011
TI  - Grb2 depletion under non-stimulated conditions inhibits PTEN, promotes Akt
      induced tumor formation and contributes to poor prognosis in ovarian cancer.
AB  - In the absence of extracellular stimulation the adaptor protein growth factor
      receptor-bound protein (Grb2) and the phospholipase Plcgamma1 compete for the
      same binding site on fibroblast growth factor receptor 2 (FGFR2). Reducing
      cellular Grb2 results in upregulation of Plcgamma1 and depletion of the
      phospholipid PI(4,5)P2. The functional consequences of this event on signaling
      pathways are unknown. We show that the decrease in PI(4,5)P2 level under non
      stimulated conditions inhibits PTEN activity leading to the aberrant activation
      of the oncoprotein Akt. This results in excessive cell proliferation and tumor
      progression in a xenograft mouse model. As well as defining a novel mechanism of
      Akt phosphorylation with important therapeutic consequences, we also demonstrate
      that differential expression levels of FGFR2, Plcgamma1 and Grb2 correlate with
      patient survival. Oncogenesis through fluctuation in the expression levels of
      these proteins negates extracellular stimulation or mutation and defines them as
      novel prognostic markers in ovarian cancer.

PMID- 26212012
TI  - Regulation of sarcoma cell migration, invasion and invadopodia formation by
      AFAP1L1 through a phosphotyrosine-dependent pathway.
AB  - Invasion and metastasis are controlled by the invadopodia, which delivers matrix
      degrading enzymes to the invasion interface permitting cancer cell penetration
      and spread into healthy tissue. We have identified a novel pathway that directs
      Lyn/Src family tyrosine kinase signals to the invadopodia to regulate sarcoma
      cell invasion via the molecule AFAP-1-like-1 (AFAP1L1), a new member of the AFAP
      (actin filament-associated protein) family. We show that AFAP1L1 can transform
      cells, promote migration and co-expression with active Lyn profoundly influences
      cell morphology and movement. AFAP1L1 intersects several invadopodia pathway
      components through its multiple domains and motifs, including the following (i)
      pleckstrin homology domains that bind phospholipids generated at the plasma
      membrane by phosphoinositide 3-kinase, (ii) a direct filamentous-actin binding
      domain and (iii) phospho-tyrosine motifs (pY136 and pY566) that specifically bind
      Vav2 and Nck2 SH2 domains, respectively. These phosphotyrosine motifs are
      essential for AFAP1L1-mediated cytoskeleton regulation. Through its interaction
      with Vav2, AFAP1L1 regulates Rac activity and downstream control of PAK1/2/3 (p21
      activated kinases) phosphorylation of myosin light chain (MLC) kinase and MLC2.
      AFAP1L1 interaction with Nck2 recruits actin-nucleating complexes. Significantly,
      in osteosarcoma cell lines, knockdown of AFAP1L1 inhibits phosphorylated MLC2
      recruitment to filamentous-actin structures, disrupts invadopodia formation, cell
      attachment, migration and invasion. These data define a novel pathway that
      directs Lyn/Src family tyrosine kinase signals to sarcoma cell invadopodia
      through specific recruitment of Vav2 and Nck2 to phosphorylated AFAP1L1, to
      control cell migration and invasion.

PMID- 26212013
TI  - Disrupting Na+, HCO3--cotransporter NBCn1 (Slc4a7) delays murine breast cancer
      development.
AB  - Increased metabolism and insufficient blood supply cause acidic waste product
      accumulation in solid cancers. During carcinogenesis, cellular acid extrusion is
      upregulated but the underlying molecular mechanisms and their consequences for
      cancer growth and progression have not been established. Genome-wide association
      studies have indicated a possible link between the Na+, HCO3--cotransporter NBCn1
      (SLC4A7) and breast cancer. We tested the functional consequences of NBCn1
      knockout (KO) for breast cancer development. NBCn1 protein expression increased
      2.5-fold during breast carcinogenesis and was responsible for the increased net
      acid extrusion and alkaline intracellular pH of breast cancer compared with
      normal breast tissue. Genetic disruption of NBCn1 delayed breast cancer
      development: tumor latency was ~50% increased while tumor growth rate was ~65%
      reduced in NBCn1 KO compared with wild-type (WT) mice. Breast cancer
      histopathology in NBCn1 KO mice differed from that in WT mice and included less
      aggressive tumor types. The extracellular tumor microenvironment in NBCn1 KO mice
      contained higher concentrations of glucose and lower concentrations of lactate
      than that in WT mice. Independently of NBCn1 genotype, the cleaved fraction of
      poly(ADP-ribose) polymerase (PARP)-1 and expression of monocarboxylate
      transporter (MCT)1 increased while phosphorylation of Akt and ERK1 decreased as
      functions of tumor volume. Cell proliferation, evaluated from Ki-67 and phospho
      histone H3staining, was ~60% lower in breast cancer of NBCn1 KO than that of WT
      mice when corrected for variations in tumor size. We conclude that NBCn1
      facilitates acid extrusion from breast cancer tissue, maintains the alkaline
      intracellular environment and promotes aggressive cancer development and growth.

PMID- 26212014
TI  - Syk-mediated tyrosine phosphorylation of mule promotes TNF-induced JNK activation
      and cell death.
AB  - The transcription factor Miz1 negatively regulates TNF-induced JNK activation and
      cell death by suppressing TRAF2 K63-polyubiquitination; upon TNF stimulation, the
      suppression is relieved by Mule/ARF-BP1-mediated Miz1 ubiquitination and
      subsequent degradation. It is not known how Mule is activated by TNF. Here we
      report that TNF activates Mule by inducing the dissociation of Mule from its
      inhibitor ARF. ARF binds to and thereby inhibits the E3 ligase activity of Mule
      in the steady state. TNF induces tyrosine phosphorylation of Mule, which
      subsequently dissociates from ARF and becomes activated. Inhibition of Mule
      phosphorylation by silencing of the Spleen Tyrosine Kinase (Syk) prevents its
      dissociation from ARF, thereby inhibiting Mule E3 ligase activity and TNF-induced
      JNK activation and cell death. Our data provides a missing link in TNF signaling
      pathway that leads to JNK activation and cell death. 

PMID- 26212015
TI  - Epigenetic silencing of GDF1 disrupts SMAD signaling to reinforce gastric cancer
      development.
AB  - Accumulating evidence reveals the effectiveness of epigenetic therapy in gastric
      cancer. However, the molecular mechanisms and targets underlying such therapeutic
      responses remain elusive. Herein, we report an aberrant yet therapeutically
      rectifiable epigenetic signaling in gastric carcinogenesis. Administration of DNA
      demethylating drug 5-aza-2'-deoxycytidine (5-aza-dC) reduced gastric cancer
      incidence by ~74% (P < 0.05) in N-nitroso-N-methylurea-treated mice. Through
      genome-wide methylation scanning, novel promoter hypermethylation-silenced and
      drug-targeted genes were identified in the resected murine stomach tumors and
      tissues. We uncovered that growth/differentiation factor 1 (Gdf1), a member of
      the transforming growth factor-beta superfamily, was silenced by promoter
      hypermethylation in control tumor-bearing mice, but became reactivated in 5-aza
      dC-treated mice (P < 0.05). In parallel, the downregulated SMAD2/3
      phosphorylation in gastric cancer was revived by 5-aza-dC in vivo. Such
      hypermethylation-dependent silencing and 5-aza-dC-mediated reactivation of GDF1
      SMAD2/3 activity was conserved in human gastric cancer cells (P < 0.05).
      Subsequent functional characterization further revealed the antiproliferative
      activity of GDF1, which was exerted through activation of SMAD2/3/4-mediated
      signaling, transcriptional controls on p15, p21 and c-Myc cell-cycle regulators
      and phosphorylation of retinoblastoma protein. Clinically, hypermethylation and
      loss of GDF1 was significantly associated with reduced phosphorylated-SMAD2/3 and
      poor survival in stomach cancer patients (P < 0.05). Taken together, we
      demonstrated a causal relationship between DNA methylation and a tumor
      suppressive pathway in gastric cancer. Epigenetic silencing of GDF1 abrogates the
      growth-inhibitory SMAD signaling and renders proliferation advantage to gastric
      epithelial cells during carcinogenesis. This study lends support to epigenetic
      therapy for gastric cancer chemoprevention and identifies a potential biomarker
      for prognosis.

PMID- 26212016
TI  - Structural investigations into the binding mode of novel neolignans Cmp10 and
      Cmp19 microtubule stabilizers by in silico molecular docking, molecular dynamics,
      and binding free energy calculations.
AB  - Microtubule stabilizers provide an important mode of treatment via mitotic cell
      arrest of cancer cells. Recently, we reported two novel neolignans derivatives
      Cmp10 and Cmp19 showing anticancer activity and working as microtubule
      stabilizers at micromolar concentrations. In this study, we have explored the
      binding site, mode of binding, and stabilization by two novel microtubule
      stabilizers Cmp10 and Cmp19 using in silico molecular docking, molecular dynamics
      (MD) simulation, and binding free energy calculations. Molecular docking studies
      were performed to explore the beta-tubulin binding site of Cmp10 and Cmp19.
      Further, MD simulations were used to probe the beta-tubulin stabilization
      mechanism by Cmp10 and Cmp19. Binding affinity was also compared for Cmp10 and
      Cmp19 using binding free energy calculations. Our docking results revealed that
      both the compounds bind at Ptxl binding site in beta-tubulin. MD simulation
      studies showed that Cmp10 and Cmp19 binding stabilizes M-loop (Phe272-Val288)
      residues of beta-tubulin and prevent its dynamics, leading to a better packing
      between alpha and beta subunits from adjacent tubulin dimers. In addition,
      His229, Ser280 and Gln281, and Arg278, Thr276, and Ser232 were found to be the
      key amino acid residues forming H-bonds with Cmp10 and Cmp19, respectively.
      Consequently, binding free energy calculations indicated that Cmp10 (-113.655
      kJ/mol) had better binding compared to Cmp19 (-95.216 kJ/mol). This study
      provides useful insight for better understanding of the binding mechanism of
      Cmp10 and Cmp19 and will be helpful in designing novel microtubule stabilizers. 

PMID- 26212017
TI  - Alcohol Consumption in Relation to Risk and Severity of Chronic Widespread Pain:
      Results From a UK Population-Based Study.
AB  - OBJECTIVE: To determine whether the reported level of alcohol consumption is
      associated with the likelihood of reporting chronic widespread pain (CWP) and,
      among persons with CWP, the associated disability. METHODS: In a population-based
      study in 2 areas of the UK, participants self-completed a postal questionnaire.
      They were classified according to whether they met the American College of
      Rheumatology definition of CWP and whether the pain was disabling (Chronic Pain
      Grade III or IV). They reported their usual level of alcohol consumption.
      Potential confounding factors on which information was available included age,
      sex, cigarette smoking, employment status, self-reported weight and height, and
      level of deprivation. RESULTS: A total of 13,574 persons participated (mean age
      55 years, 57% women) of whom 2,239 (16.5%) had CWP; 28% reported never regularly
      consuming alcohol, 28% reported consuming up to 5 units/week, 20% reported 6-10
      units/week, and 24% reported >10 units/week. Among persons with CWP, disability
      was strongly linked to level of alcohol consumption. Prevalence of disability
      decreased with increasing alcohol consumption up to 35 units/week (odds ratio
      [OR]21-35 units alcohol/week versus never drinkers 0.33 [95% confidence interval
      (95% CI) 0.19-0.58]) adjusted for confounders. A similar relationship was found
      between reporting CWP and level of alcohol consumption (adjusted OR21-35 units
      alcohol/week versus never drinkers 0.76 [95% CI 0.61-0.94]). CONCLUSION: This
      study has demonstrated strong associations between level of alcohol consumption
      and both CWP and related disabilities. However, the available evidence does not
      allow us to conclude that the association is causal. The strength of the
      associations means that specific studies to examine this potential relationship
      are warranted.

PMID- 26212018
TI  - Frustration Sculpts the Early Stages of Protein Folding.
AB  - The funneled energy landscape theory implies that protein structures are
      minimally frustrated. Yet, because of the divergent demands between folding and
      function, regions of frustrated patterns are present at the active site of
      proteins. To understand the effects of such local frustration in dictating the
      energy landscape of proteins, here we compare the folding mechanisms of the two
      alternative spliced forms of a PDZ domain (PDZ2 and PDZ2as) that share a nearly
      identical sequence and structure, while displaying different frustration
      patterns. The analysis, based on the kinetic characterization of a large number
      of site-directed mutants, reveals that although the late stages for folding are
      very robust and biased by native topology, the early stages are more malleable
      and dominated by local frustration. The results are briefly discussed in the
      context of the energy-landscape theory. 

PMID- 26212019
TI  - Mannose-Binding Lectin and Diabetic Nephropathy in Type 1 Diabetes.
AB  - OBJECTIVE: The aim of this study was to investigate serum levels of mannose
      binding lectin (MBL) in type 1 diabetes with diabetic nephropathy (DN) and
      persistent normoalbuminuria (PN). METHOD: Serum MBL levels were determined in 224
      type 1 diabetes with overt nephropathy and 224 type 1 diabetes with PN matched
      for sex, age, and duration of diabetes The prediction value of MBL was compared
      with hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein (Hs-CRP) and
      other known predictors. Multivariate analyses were performed using logistic
      regression models. RESULTS: The serum MBL levels were significantly higher in
      diabetes with DN as compared to with PN (P < 0.0001). Based on the receiver
      operating characteristic (ROC) curve, the optimal cutoff value of serum MBL
      levels as an indicator for diagnosis of DN was projected to be 1,680 MUg/l, which
      yielded a sensitivity of 75.4% and a specificity of 78.8%, with the area under
      the curve at 0.768 (95% confidence interval [CI], 0.724-0.815). Multivariate
      logistic regression analysis adjusted for common factors showed that serum MBL
      level >= 1,680 MUg/l was an independent indictor of DN (odds ratio [OR] = 6.99;
      95% CI: 2.83-17.15). CONCLUSION: In type 1 diabetic patient, evaluated serum
      levels of MBL can be seen as an independent marker of DN even after correcting
      for possible confounding factors.

PMID- 26212020
TI  - Liver stiffness plus platelet count can be used to exclude high-risk oesophageal
      varices.
AB  - BACKGROUND/AIMS: Endoscopic screening for high-risk gastro-oesophageal varices
      (GOV) is recommended for compensated cirrhotic patients with transient
      elastography identifying increasing numbers of patients with cirrhosis without
      portal hypertension. Using liver stiffness measurement (LSM) +/- platelet count,
      the aim was to develop a simple clinical rule to exclude the presence of high
      risk GOV in patients with Child-Pugh A cirrhosis. METHODS: A retrospective
      analysis of 71 patients with Child-Pugh A cirrhosis diagnosed by transient
      elastography (LSM >13.6 kPa) who underwent screening gastroscopy was conducted. A
      predictive model using LSM +/- platelet count was assessed to exclude the
      presence of high-risk GOV (diameter >5 mm and/or the presence of high-risk
      stigmata) and validated using a second cohort of 200 patients from two
      independent centres. RESULTS: High-risk GOV were present in 10 (15%) and 16 (8%)
      of the training and validation cohorts, respectively, which was associated with
      LSM and Pl count (P < 0.05). A combined model based on LSM and Pl count was more
      accurate for excluding the presence of high-risk GOV than either alone (training
      cohort AUROC: 0.87 [0.77-0.96] vs. 0.78 [0.65-0.92] for LSM and 0.71 [0.52-0.90]
      for platelets) with the combination of LSM <=25 kPa and Pl >=100 having a NPV of
      100% in both the training and validation cohorts. A total of 107 (39%) patients
      meet this criterion. CONCLUSION: The combination of LSM <=25 kPa and Pl >=100 can
      be used in clinical practice to exclude the presence of high-risk GOV in patients
      with Child-Pugh A cirrhosis.

PMID- 26212021
TI  - Characteristics and practices of Traditional Chinese Medicine retail shops in
      London, UK: A cross-sectional study using an observational approach.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) is a popular
      form of ethnomedicine in the UK, and is accessed by Western, Chinese and other
      ethnic groups. The current regulatory regime does not effectively protect the
      public against poor-quality and unsafe TCMs. Understanding ethnopharmacological
      information on how TCM is promoted and practiced may help to inform initiatives
      aimed at ensuring the safe use of TCMs in the UK, and put laboratory-based
      ethnopharmacological investigations of TCMs in a broader context. AIM OF THE
      STUDY: This study aimed to examine the characteristics and practices of TCM
      retail outlets in London, UK, and to identify factors relevant to the safe use of
      TCM in the UK. MATERIALS AND METHODS: TCM retail outlets ('shops') in London, UK,
      were identified using a systematic approach. A structured questionnaire including
      questions on shop business type was used to recruit participant shops. Shops
      consenting to participate were visited within six weeks of providing consent. A
      piloted semi-structured questionnaire on shop characteristics was used for data
      collection following observation. The British National Formulary 53 was used to
      classify medical conditions/uses for TCMs promoted in the shops. Data were stored
      and analysed using MS Access 2003, MS Excel 2003 and SPSS 13. RESULTS: In total,
      54 TCM shops in London were identified, of which 94% offered TCM consultations
      with a TCM practitioner. Detailed characteristics were described within 35/50
      shops that gave consent to observing their premises. Most shops labelled and
      displayed over 150 Chinese Materia Medica (CMMs; crude materials, particularly
      herbs) for dispensing after consultations with a TCM practitioner. Medical
      conditions/uses and Patent Chinese Medicines (PCMs) were commonly promoted. In
      total, 794 occurrences of 205 different medical conditions/uses (median=32,
      QL=19, QU=48) were identified. These conditions/uses most commonly related to the
      following therapeutic systems: central nervous system (160/794, 20.2%);
      musculoskeletal and joint disease (133/794, 16.8%); obstetrics, gynaecology, and
      urinary-tract disorders (122/794, 15.4%); skin (102/794, 12.9%); gastrointestinal
      system (62/794, 7.8%). Specific conditions/uses that were frequently promoted
      included eczema (19/23 shops, 82.6%), arthritis (18/23, 78.3%), acne (17/23,
      73.9%), obesity/weight loss/slimming (17/23, 73.9%) and psoriasis (17/23, 73.9%).
      Claimed conditions/uses included some serious medical conditions (e.g. diabetes,
      cancer and hypertension) and those focusing on vulnerable groups (e.g. children's
      diseases and pregnancy treatments). CONCLUSIONS: TCM shops in London, UK,
      typically displayed names of a wide range of medical conditions/uses for TCMs
      using readily understandable medical terms, implying TCM can be used to prevent
      or treat these conditions. However, many of these advertisements did not comply
      with UK regulations on medical claims for herbal medicines. Future studies should
      explore how these advertisements influence consumers' decisions to access TCM in
      the UK, practices of TCM shop staff towards the supply of TCMs in the UK, and
      what are the health implications at the individual and population levels.

PMID- 26212022
TI  - Synergistic effects of Artemisia iwayomogi and Curcuma longa radix on high-fat
      diet-induced hyperlipidemia in a mouse model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plants Artemisia iwayomogi and
      Curcuma longa radix are both used to treat hyperlipidemia in traditional Korean
      and Chinese medicine. AIM OF THE STUDY: To evaluate the anti-hyperlipidemic
      effects of the 30% ethanol extracts of A. iwayomogi (AI), C. longa (CL), and the
      mixture of A. iwayomogi and C. longa (ACE), using a high-fat diet-induced
      hyperlipidemia model. MATERIALS AND METHODS: Six of seven groups of C57BL/6N male
      mice (i.e., not including the naive group) were fed a high-fat diet freely for 10
      weeks. Of these six groups, five (i.e., not including the control group) were
      administered a high-fat diet supplemented with AI (100mg/kg), CL (100mg/kg), ACE
      (50 or 100mg/kg), or Lipitor (20mg/kg). Serum lipid profiles, obesity-related
      markers, hepatic steatosis, hepatic gene expression, and oxidative stress markers
      were analyzed. RESULTS: AI, CL, and ACE were associated with significant effects
      on serum lipid profiles (total cholesterol [TC] and triglyceride), body, liver
      and peritoneal adipose tissue weights, hepatic lipid accumulation, and oxidative
      stress biomarkers. ACE at 100mg/kg was associated with significantly greater
      improvements in serum TC and triglyceride, hepatic triglyceride, epididymal
      adipocyte size, and oxidative stress biomarkers, compared with AI and CL. AI, CL
      and ACE normalized lipid synthesis-associated gene expression (peroxisome
      proliferator-activated receptor gamma, fatty acid synthase, sterol regulatory
      element-binding transcription factor-1c, and peroxisome proliferator-activated
      receptor alpha). CONCLUSION: ACE exhibits anti-hyperlipidemia properties and is
      associated with partially synergistic effects compared with AI or CL alone.

PMID- 26212023
TI  - The impact of school nonresponse on substance use prevalence estimates - Germany
      as a case study.
AB  - BACKGROUND: The European School Survey Project on Alcohol and Other Drugs (ESPAD)
      is a survey study that collects comparable data on substance use of students aged
      15-16 years old in European countries. The present study aims at investigating
      the impact of school refusal to participate in ESPAD on substance use prevalence
      estimates. METHODS: Data came from the 2007 German ESPAD study; the sample
      consisted of 12,246 students in 552 schools within seven German federal states. A
      simulation approach was used in order to study the effects of systematic
      exclusion of participating schools on prevalence estimates of key ESPAD outcomes
      including the use of tobacco, alcohol, cannabis, and other illegal drugs.
      RESULTS: The systematic exclusion of schools based on city-, school-, and class
      size, school environment, and schools' substance use policies resulted in
      significant changes in prevalence estimates in 23 of 25 examined combinations of
      selection criterion and outcome. Yet, these effects were small, with differences
      remaining below three percentage points around the original estimates.
      CONCLUSIONS: This simulation approach suggests that nonparticipation of schools
      in surveys on students' substance use in Germany does not largely affect the
      validity of resulting prevalence estimates. Even a reduced number of schools may
      be sufficient to gain valid prevalence figures.

PMID- 26212024
TI  - Towards highest peak intensities for ultra-short MeV-range ion bunches.
AB  - A laser-driven, multi-MeV-range ion beamline has been installed at the GSI
      Helmholtz center for heavy ion research. The high-power laser PHELIX drives the
      very short (picosecond) ion acceleration on MUm scale, with energies ranging up
      to 28.4 MeV for protons in a continuous spectrum. The necessary beam shaping
      behind the source is accomplished by applying magnetic ion lenses like solenoids
      and quadrupoles and a radiofrequency cavity. Based on the unique beam properties
      from the laser-driven source, high-current single bunches could be produced and
      characterized in a recent experiment: At a central energy of 7.8 MeV, up to 5 *
      10(8) protons could be re-focused in time to a FWHM bunch length of tau = (462 +/
      40) ps via phase focusing. The bunches show a moderate energy spread between 10%
      and 15% (DeltaE/E0 at FWHM) and are available at 6 m distance to the source und
      thus separated from the harsh laser-matter interaction environment. These
      successful experiments represent the basis for developing novel laser-driven ion
      beamlines and accessing highest peak intensities for ultra-short MeV-range ion
      bunches.

PMID- 26212025
TI  - The impacts of organic matter on the distribution and methylation of mercury in a
      hydroelectric reservoir in Wujiang River, Southwest China.
AB  - To understand the impacts of organic matter on the geochemical processing of Hg
      in a hydroelectric reservoir, spatial and seasonal distributions of total mercury
      (THg) and methylmercury (MeHg) in both solid and liquid phases of sediment cores
      were investigated in the Wujiangdu Reservoir in Guizhou Province, China. Four
      sampling sites with different intensities of cage aquaculture activities were
      chosen and were evenly distributed from upstream to downstream of the Wujiangdu
      Reservoir. Elevated MeHg concentrations and the high percentage of MeHg in solid
      and liquid phases of the surface sediment demonstrated that the active Hg
      methylation process occurred downstream of the Wujiangdu Reservoir. In contrast,
      the absence of obvious peaks for MeHg in sediment from the upper reaches of the
      Wujiangdu Reservoir, consistent with low levels of organic matter, suggested that
      production of MeHg was limited. In sediment with high organic matter content,
      reduction occurred closer to the sediment surface, resulting in maximum MeHg
      concentration in these layers. The correlation between MeHg and organic carbon
      implied that organic matter content in the sediment originating from cage
      aquaculture activities can help to predict MeHg production rates in reservoirs,
      which could be used to assess possible MeHg contamination in a reservoir
      ecosystem.

PMID- 26212026
TI  - In vitro cytotoxicity of superparamagnetic iron oxide nanoparticles on neuronal
      and glial cells. Evaluation of nanoparticle interference with viability tests.
AB  - Superparamagnetic iron oxide nanoparticles (ION) have attracted great interest
      for use in several biomedical fields. In general, they are considered
      biocompatible, but little is known of their effects on the human nervous system.
      The main objective of this work was to evaluate the cytotoxicity of two ION
      (magnetite), coated with silica and oleic acid, previously determining the
      possible interference of the ION with the methodological procedures to assure the
      reliability of the results obtained. Human neuroblastoma SHSY5Y and glioblastoma
      A172 cells were exposed to different concentrations of ION (5-300 ug ml(-1)),
      prepared in complete and serum-free cell culture medium for three exposure times
      (3, 6 and 24 h). Cytotoxicity was evaluated by means of the MTT, neutral red
      uptake and alamar blue assays. Characterization of the main physical-chemical
      properties of the ION tested was also performed. Results demonstrated that both
      ION could significantly alter absorbance readings. To reduce these interferences,
      protocols were modified by introducing additional washing steps and cell-free
      systems. Significant decreases in cell viability were observed for both cell
      lines in specific conditions by all assays. In general, oleic acid-coated ION
      were less cytotoxic than silica-coated ION; besides, a serum-protective effect
      was observed for both ION studied and cell lines. These results contribute to
      increase the knowledge of the potential harmful effects of ION on the human
      nervous system. Understanding these effects is essential to establish
      satisfactory regulatory policies on the safe use of magnetite nanoparticles in
      biomedical applications.

PMID- 26212027
TI  - Reply to "Points to be considered when using transient elastography for diagnosis
      of portal hypertension according to the Baveno's VI consensus".

PMID- 26212028
TI  - Peri-scoping the biliary tree reveals stem cell activation in peribiliary glands
      in primary sclerosing cholangitis.

PMID- 26212030
TI  - Prognostic impact of surgery and radiofrequency ablation on single nodular HCC ?5
      cm: Cohort study based on serum HCC markers.
AB  - BACKGROUND & AIMS: Serological markers of hepatocellular carcinoma (HCC) indicate
      its invasiveness. We aimed to investigate whether the prognostic impact of
      surgical resection (SR) and radiofrequency thermal ablation (RFA) on patients
      with single nodular HCC ?5cm were different regarding positive conditions of the
      following three HCC markers: alpha-fetoprotein (AFP); lens culinaris agglutinin
      reactive fraction of AFP; and des-gamma-carboxy prothrombin. METHODS: This study
      reviewed 296 patients with single nodular HCC ?5cm with Child-Pugh grade A
      between 2001 and 2011 (SR, n=136; RFA, n=160). Based on positive conditions of
      previous HCC markers (defined as non-positive, single-positive, double-positive,
      and triple-positive), overall survival (OS) and prognostic factors were analyzed.
      RESULTS: Five-year OS rates of SR and RFA among all patients were 70.1% and
      69.8%, respectively (p=0.14). However, when stratified by the positive conditions
      of three HCC markers, their rates of non-, single-, double-, and triple-positive
      patients were 60.6%, 78.2%, 54.2%, and 75.9% in the SR group, whereas rates were
      83.3%, 75.7%, 62.2%, and 47.6% in the RFA group (p values between SR and RFA of
      each tumor marker condition were 0.45, 0.10, 0.77, and <0.01, respectively).
      Multivariate analyses showed that RFA itself became an independent prognostic
      factor in the triple-positive group, with an odds ratio of 1.78 (95% confidence
      interval, 1.16-2.72). CONCLUSIONS: Positive conditions of three HCC markers
      differently influenced survival rates of those who underwent SR and RFA when
      treating single nodular HCC ?5cm. RFA itself became an independent prognostic
      risk when all three HCC markers were positive. Preoperative evaluation of
      multiple HCC markers might become an index for selecting treatment modalities.

PMID- 26212029
TI  - Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567
      phosphorylation in human obstructive cholestasis.
AB  - BACKGROUND & AIMS: Multidrug resistance-associated protein 2 (MRP2) excretes
      conjugated organic anions including bilirubin and bile acids. Malfunction of MRP2
      leads to jaundice in patients. Studies in rodents indicate that Radixin plays a
      critical role in determining Mrp2 canalicular membrane expression. However, it is
      not known how human hepatic MRP2 expression is regulated in cholestasis. METHODS:
      We assessed liver MRP2 expression in patients with obstructive cholestasis caused
      by gallstone blockage of bile ducts, and investigated the regulatory mechanism in
      HepG2 cells. RESULTS: Western blot detected that liver MRP2 protein expression in
      obstructive cholestatic patients (n=30) was significantly reduced to 25% of the
      non-cholestatic controls (n=23). Immunoprecipitation identified Ezrin but not
      Radixin associating with MRP2 in human livers, and the increased amount of
      phospho-Ezrin Thr567 was positively correlated with the amount of co-precipitated
      MRP2 in cholestatic livers, whereas Ezrin and Radixin total protein levels were
      unchanged in cholestasis. Further detailed studies indicate that Ezrin Thr567
      phosphorylation plays an important role in MRP2 internalization in HepG2 cells.
      Since increased expression of PKCalpha, delta and epsilon were detected in these
      cholestatic livers, we further confirmed that these PKCs stimulated Ezrin
      phosphorylation and reduced MRP2 membrane expression in HepG2 cells. Finally, we
      identified GP78 as the key ubiquitin ligase E3 involved in MRP2 proteasome
      degradation. CONCLUSIONS: Activation of liver PKCs during cholestasis leads to
      Ezrin Thr567 phosphorylation resulting in MRP2 internalization and degradation
      where ubiquitin ligase E3 GP78 is involved. This process provides a mechanistic
      explanation for jaundice seen in patients with obstructive cholestasis.

PMID- 26212031
TI  - Synthesis and Evaluation of Gd(III) -Based Magnetic Resonance Contrast Agents for
      Molecular Imaging of Prostate-Specific Membrane Antigen.
AB  - Magnetic resonance (MR) imaging is advantageous because it concurrently provides
      anatomic, functional, and molecular information. MR molecular imaging can combine
      the high spatial resolution of this established clinical modality with molecular
      profiling in vivo. However, as a result of the intrinsically low sensitivity of
      MR imaging, high local concentrations of biological targets are required to
      generate discernable MR contrast. We hypothesize that the prostate-specific
      membrane antigen (PSMA), an attractive target for imaging and therapy of prostate
      cancer, could serve as a suitable biomarker for MR-based molecular imaging. We
      have synthesized three new high-affinity, low-molecular-weight Gd(III) -based
      PSMA-targeted contrast agents containing one to three Gd(III)  chelates per
      molecule. We evaluated the relaxometric properties of these agents in solution,
      in prostate cancer cells, and in an in vivo experimental model to demonstrate the
      feasibility of PSMA-based MR molecular imaging.

PMID- 26212032
TI  - Phytofabrication of bioinspired zinc oxide nanocrystals for biomedical
      application.
AB  - In the present study, we investigated a novel green route for synthesis of zinc
      oxide nanoparticles (ZnO NPs) using the extract of young cones of Pinus
      densiflora as a reducing agent. Standard characterization studies were carried
      out to confirm the obtained product using UV-Vis spectra, SEM-EDS, FTIR, and XRD.
      TEM images showed that various shapes of ZnO NPs were synthesized, including
      hexagonal (wurtzite), triangular, spherical, and oval-shaped particles, with
      average sizes between 10 and 100 nm. The synthesized ZnO NPs blended with the
      young pine cone extract have very good activity against bacterial and fungal
      pathogens, similar to that of commercial ZnO NPs. 

PMID- 26212033
TI  - Dermoscopy of idiopathic guttate hypomelanosis.

PMID- 26212034
TI  - The effect of snacking and eating frequency on dietary quality in British
      adolescents.
AB  - PURPOSE: To describe the effects of number of eating occasions and snacks on
      dietary quality (DQ), defined as adherence to dietary recommendations. METHODS: A
      sample of 884 adolescents (11-18 years) in the UK National Diet and Nutrition
      Survey (NDNS) were included. The Diet Quality Index for Adolescents (DQI-A) was
      implemented. The total number of eating occasions and snacks was frequency of
      food or beverages consumed over 24 h and frequency of foods or beverages consumed
      outside of the three mealtimes, respectively. Results were generated with and
      without low-energy food under 210 kJ (50 kcal). Regression models were generated
      with DQ score as the outcome variable and number of eating occasions and snacks
      as predictors. RESULTS: The mean (95 % CI) DQ score was 31.1 % (30.2, 32.0). The
      mean number of eating occasions and snacks was 7.5 (7.3, 7.7) and 2.6 (2.6, 2.7)
      times/day, respectively. When low-energy events were excluded, the mean number of
      eating occasions and snacks reduced to 6.2 (6.1, 6.4) and 2.0 (2.0, 2.1)
      times/day, respectively. DQ score increased by 0.74 points (0.42, 1.05; p < 0.01)
      and 0.55 points (-0.08, 0.69; p = 0.17) for total eating occasions and snacks,
      respectively. When low-energy events were excluded, DQ score increased by 0.30
      points (-0.84, 0.69; p = 0.13) for each eating occasion and decreased by 1.20
      points (-2.1, -0.3; p < 0.01) for each snack. CONCLUSION: Eating more frequently
      improves dietary quality especially if some eating occasions are low in energy. A
      focus on replacing high-energy snacks with low-energy alternatives rather than
      reducing the number of eating occasions may result in improved dietary quality in
      adolescents.

PMID- 26212035
TI  - DDX5 promotes proliferation and tumorigenesis of non-small-cell lung cancer cells
      by activating beta-catenin signaling pathway.
AB  - The DEAD-box-protein DDX5 is an ATP-dependent RNA helicase that is frequently
      overexpressed in various cancers and acts as a transcriptional co-activator of
      several transcription factors, including beta-catenin. DDX5 is reported to be
      involved in cancer progression by promoting cell proliferation and epithelial
      mesenchymal transition. However, the clinical significance and biological role of
      DDX5 in non-small-cell lung cancer (NSCLC) remain largely unknown. In this study,
      we examined the expression of DDX5 in clinical NSCLC samples, investigated its
      role in regulating NSCLC cell proliferation and tumorigenesis, and explored the
      possible molecular mechanism. We found that DDX5 was significantly overexpressed
      in NSCLC tissues as compared with the matched normal adjacent tissues. In
      addition, overexpression of DDX5 was associated with advanced clinical stage,
      higher Ki67 index, and shorter overall survival in NSCLC patients. Upregulation
      of DDX5 promoted proliferation of NSCLC cells in vitro and growth of NSCLC
      xenografts in vivo, whereas downregulation of DDX5 showed the opposite effects.
      Furthermore, DDX5 directly interacted with beta-catenin, promoted its nuclear
      translocation, and co-activated the expression of cyclin D1 and c-Myc. beta
      catenin silencing significantly abrogated DDX5-induced cyclin D1 and c-Myc
      expression and proliferation in NSCLC cells. Interestingly, DDX5 and cyclin D1
      expression followed positive correlation in the same set of NSCLC samples. These
      findings indicated that DDX5 played an important role in the proliferation and
      tumorigenesis of NSCLC cells by activating the beta-catenin signaling pathway.
      Therefore, DDX5 may serve as a novel prognostic marker and potential therapeutic
      target in the treatment of NSCLC.

PMID- 26212036
TI  - Identification of seven novel HLA class I alleles in New Zealand.
AB  - Seven new HLA class I alleles have been identified in the New Zealand population
      in the process of routine HLA typing and they are described here. Unusual bead
      positivity in Luminex typing identified potential new alleles in a bone marrow
      registry donor (B*40:285) and two HIV patients prior to abacavir prescription
      (B*14:02:09, B*41:29). In addition, four new class I alleles were identified
      through class I sequencing-based typing (SBT) outside of exons 2 and 3. One
      mutation was identified in exon 4 (new allele C*12:125) and three have been found
      in exon 5, an exon rarely sequenced. Two stem cell transplant recipients
      (B*07:02:45, C*03:279) had novel mutations in exon 5 and one was found in exon 5
      of a potentially matched unrelated donor from DKMS, previously thought to be
      B*40:02:01 (B*40:303). 

PMID- 26212038
TI  - Factors influencing sexually transmitted infections among adolescents in South
      Korea.
AB  - BACKGROUND: No data exist regarding the sexually transmitted infection (STI) rate
      in adolescents aged 12-15 in South Korea. Only a Korean few studies have
      attempted to investigate the factors influencing sexually transmitted infections
      among adolescents. AIM: The purpose of this study was to investigate the self
      reported sexually transmitted infection contraction rate and analyse individual
      and family factors that influence this rate among middle school students aged 12
      15 in South Korea. METHODS: Using statistics from the 8th Korea Youth Risk
      Behavior Web-based Survey, secondary data analysis was conducted. The study
      sample consisted of 714 individuals who had reported initiating sexual
      intercourse. RESULTS: The rate of self-reported sexually transmitted contraction
      was 13.5%. The following factors predicted STI contraction: second year of middle
      school, excellent academic achievement, habitual or purposeful drug use, first
      intercourse before middle school, intercourse after drinking alcohol, weekly
      allowance, and living without family predicted sexually transmitted infection
      contraction. LIMITATIONS: The parental data were collected by the self-reported
      surveys in a cross-sectional manner and questions of STI contraction and
      intercourse after drinking may have confused the subjects. CONCLUSION: We need to
      utilize these predictors in providing adolescents with sexual health
      interventions and establishing adolescent sexual health policies. IMPLICATIONS
      FOR NURSING AND HEALTH POLICIES: Increased sex education and employment of a
      school nurse in each middle school are needed. High-risk students need to be
      monitored given the predictors of sexually transmitted infection contraction, and
      the school health personnel need to inform female students and their parents the
      importance of seeing a gynaecologist for regular check-ups.

PMID- 26212039
TI  - Multiple astrovirus MLB1, MLB2, VA2 clades, and classic human astrovirus in
      children with acute gastroenteritis in Japan.
AB  - This study investigated the genetic variability of astroviruses in children with
      acute gastroenteritis in Japan in 2012 to 2013. A total of 330 fecal specimens
      collected from children with diarrhea were tested for astroviruses using RT-PCR
      and nucleotide sequencing techniques. Among the tested specimens, 54 (16.4%) were
      positive for astrovirus. Three different phylogenetic clades were detected. MLB
      was the most predominant clade (35 samples), followed by classic astrovirus (17
      samples), and VA astrovirus (2 samples). Two types of MLB were identified (MLB1
      and MLB2), while classic astroviruses were HAstV1 and HAstV4. Two VA astroviruses
      were identified as VA2.

PMID- 26212040
TI  - The influence of MicroRNA-150 in Osteoblast Matrix Mineralization.
AB  - This study investigated the influence of miR-150 expression on osteoblast matrix
      mineralization and its mechanisms. The mouse osteoblast cell line MC3T3-E1 was
      used as an in vitro model of bone formation. On the fifth day of mineralization,
      transfection experiments using agomiR-150, agomiR-NC, antagomiR-150 antagomiR-NC,
      and mock groups were set up to test the effects of miR-150 in MC3T3-E1 model. The
      mRNA and protein levels of OC, ALP, type I collagen, and OPN were measured by qRT
      PCR and ELISA. Matrix mineralization was detected by alizarin red S (ARS)
      staining and flow cytometry was employed to quantify apoptosis in each group. RT
      PCR and Western blot were applied to detect the expression of target gene MMP14.
      Our results demonstrated that the endogenous expression levels of miR-150, OC,
      ALP, type I collagen, and OPN in MC3T3-E1 cells increased steadily. Exogenous
      expressions of agomiR-150 and antagomiR-150 can significantly up-/down-regulate,
      respectively, the expression level of miR-150 in MC3T3-E1 cells. Compared with
      the mock group, higher expression levels of OC, ALP, type I collagen, and OPN
      mRNA were observed in the agomiR-150 group, while lower mRNA expression levels of
      OC, ALP, type I collagen, and OPN were found in the antagomiR-150 group. Based on
      these results, potential miR-150 targeted genes are discussed. Our results showed
      that miR-150 supports the osteoblastic phenotype related to osteoblast function
      and bone mineralization. Thus, miR-150 may have potential therapeutic
      applications in promoting bone formation in certain disease settings, such as in
      osteoporosis and in elderly patients.

PMID- 26212041
TI  - Poverty, Pregnancy, and Birth Outcomes: A Study of the Earned Income Tax Credit.
AB  - BACKGROUND: Economic interventions are increasingly recognised as a mechanism to
      address perinatal health outcomes among disadvantaged groups. In the US, the
      earned income tax credit (EITC) is the largest poverty alleviation programme.
      Little is known about its effects on perinatal health among recipients and their
      children. We exploit quasi-random variation in the size of EITC payments to
      examine the effects of income on perinatal health. METHODS: The study sample
      includes women surveyed in the 1979 National Longitudinal Survey of Youth (n =
      2985) and their children born during 1986-2000 (n = 4683). Outcome variables
      include utilisation of prenatal and postnatal care, use of alcohol and tobacco
      during pregnancy, term birth, birthweight, and breast-feeding status. We first
      examine the health effects of both household income and EITC payment size using
      multivariable linear regressions. We then employ instrumental variables analysis
      to estimate the causal effect of income on perinatal health, using EITC payment
      size as an instrument for household income. RESULTS: We find that EITC payment
      size is associated with better levels of several indicators of perinatal health.
      Instrumental variables analysis, however, does not reveal a causal association
      between household income and these health measures. CONCLUSIONS: Our findings
      suggest that associations between income and perinatal health may be confounded
      by unobserved characteristics, but that EITC income improves perinatal health.
      Future studies should continue to explore the impacts of economic interventions
      on perinatal health outcomes, and investigate how different forms of income
      transfers may have different impacts.

PMID- 26212042
TI  - Periventricular white matter hyperintensities and the risk of dementia: a CREDOS
      study.
AB  - BACKGROUND: Cerebral white matter hyperintensities (WMH) are prevalent incident
      findings on brain MRI scans among elderly people and have been consistently
      implicated in cognitive dysfunction. However, differential roles of WMH by region
      in cognitive function are still unclear. The aim of this study was to ascertain
      the differential role of regional WMH in predicting progression from mild
      cognitive impairment (MCI) to different subtypes of dementia. METHODS:
      Participants were recruited from the Clinical Research Center for Dementia of
      South Korea (CREDOS) study. A total of 622 participants with MCI diagnoses at
      baseline and follow-up evaluations were included for the analysis. Initial MRI
      scans were rated for WMH on a visual rating scale developed for the CREDOS.
      Differential effects of regional WMH in predicting incident dementia were
      evaluated using the Cox proportional hazards model. RESULTS: Of the 622
      participants with MCI at baseline, 139 patients (22.3%) converted to all-cause
      dementia over a median of 14.3 (range 6.0-36.5) months. Severe periventricular
      WMH (PWMH) predicted incident all-cause dementia (Hazard ratio (HR) 2.22; 95%
      confidence interval (CI) 1.43-3.43) and Alzheimer's disease (AD) (HR 1.86; 95% CI
      1.12-3.07). Subcortical vascular dementia (SVD) was predicted by both PWMH (HR
      16.14; 95% CI 1.97-132.06) and DWMH (HR 8.77; 95% CI 1.77-43.49) in more severe
      form (>= 10 mm). CONCLUSIONS: WMH differentially predict dementia by region and
      severity. Our findings suggest that PWMH may play an independent role in the
      pathogenesis of dementia, especially in AD.

PMID- 26212043
TI  - The Risk GP Model: the standard model of prediction in medicine.
AB  - With the ascent of modern epidemiology in the Twentieth Century came a new
      standard model of prediction in public health and clinical medicine. In this
      article, we describe the structure of the model. The standard model uses
      epidemiological measures-most commonly, risk measures-to predict outcomes
      (prognosis) and effect sizes (treatment) in a patient population that can then be
      transformed into probabilities for individual patients. In the first step, a risk
      measure in a study population is generalized or extrapolated to a target
      population. In the second step, the risk measure is particularized or transformed
      to yield probabilistic information relevant to a patient from the target
      population. Hence, we call the approach the Risk Generalization-Particularization
      (Risk GP) Model. There are serious problems at both stages, especially with the
      extent to which the required assumptions will hold and the extent to which we
      have evidence for the assumptions. Given that there are other models of
      prediction that use different assumptions, we should not inflexibly commit
      ourselves to one standard model. Instead, model pluralism should be standard in
      medical prediction. 

PMID- 26212044
TI  - Dual antiviral therapy for HIV and hepatitis C - drug interactions and side
      effects.
AB  - INTRODUCTION: Roughly 20% of HIV-positive persons worldwide are coinfected with
      hepatitis C virus (HCV). The recent advent of direct-acting antivirals (DAA) that
      cure most hepatitis C patients has attracted much attention. Knowledge on drug
      interactions between DAA and antiretrovirals (ARV) may allow maximizing antiviral
      efficacy while minimizing drug-related toxicities. AREAS COVERED: We review the
      most frequent side effects and clinically significant drug interactions between
      DAA and ARV. We further discuss how they can be prevented and managed in HIV/HCV
      coinfected patients. EXPERT OPINION: The safety profile of current DAA and the
      most recently approved ARV is quite favorable. Interactions between DAA and ARV
      could be frequent in clinical practice. The most common drug interactions affect
      drug metabolism by inducing or inhibiting the cytochrome P450 system, leading to
      abnormal drug exposures. Throughout this mechanism HCV and HIV protease
      inhibitors interact, especially when co-formulated with ritonavir as a
      pharmacoenhancer, and non-nucleoside HCV and HIV polymerase inhibitors. In
      contrast, HIV and HCV nucleos(t)ide polymerase inhibitors, and most HCV NS5A
      inhibitors (i.e., ledipasvir) and HIV integrase inhibitors (i.e., dolutegravir),
      do not or only marginally affect CYP450, and therefore are free of significant
      drug interactions. Exposure to HIV and HCV nucleos(t)ide analogues (i.e.,
      tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of
      drug transporters (i.e., P-glycoprotein).

PMID- 26212047
TI  - Resistance mechanisms in photodynamic therapy.

PMID- 26212049
TI  - An overview of selected current approaches to the characterization of aqueous
      inorganic clusters.
AB  - This Perspective article highlights some of the traditional and non-traditional
      analytical tools that are presently used to characterize aqueous inorganic
      nanoscale clusters and polyoxometalate ions. The techniques discussed in this
      article include nuclear magnetic resonance spectroscopy (NMR), small angle X-ray
      scattering (SAXS), dynamic and phase analysis light scattering (DLS and PALS),
      Raman spectroscopy, and quantum mechanical computations (QMC). For each method we
      briefly describe how it functions and illustrate how these techniques are used to
      study cluster species in the solid state and in solution through several
      representative case studies. In addition to highlighting the utility of these
      techniques, we also discuss limitations of each approach and measures that can be
      applied to circumvent such limits as it pertains to aqueous inorganic cluster
      characterization. 

PMID- 26212050
TI  - The professional role of a dental hygienist in Finland - educators' views.
AB  - OBJECTIVES: To assess the role and envisioned professional identity of the dental
      hygienist in the eyes of their educators at the Finnish training institutes and
      to determine the need for any changes and improvements. METHODS: A cross
      sectional explorative study used as its main method interviews conducted in 2012
      2013 among educators of dental hygienists in Finland. Leading representatives of
      dental hygienist training at all vocational health institutes, dental schools and
      centres of health education were asked to participate in the study. The
      interviews consisted of two parts: a self-administered questionnaire and a semi
      structured interview. The qualitative data were analysed with thematic analysis.
      The inductive theoretical approach served to categorize the data based on
      emergent themes and patterns. RESULTS: The educators held a general respect and
      appreciation for the dental hygienist profession. They felt that dental
      hygienists' skills ought to see more use in orthodontics and in preventive care
      than is customary today, including in tobacco prevention and smoking cessation as
      well as in dietary instruction among adults. The traditional role of the dental
      hygienist and the evolving scope of dental practice seemed mismatched. Concern
      about the lack of clarity regarding the division of labour in clinical practice
      was expressed. The respondents were convinced of that the division of labour in
      the public sector differs from that in the private sector. CONCLUSION: The
      educators thought that the role of the dental hygienist and the evolving scope of
      dental practice were partly mismatched. A reassessment of stakeholder involvement
      in the development of training curricula is urgently needed.

PMID- 26212048
TI  - Messenger RNA encoding constitutively active Toll-like receptor 4 enhances
      effector functions of human T cells.
AB  - Adoptive T cell therapy of cancer employs a large number of ex-vivo-propagated T
      cells which recognize their targets either by virtue of their endogenous T cell
      receptor (TCR) or via genetic reprogramming. However, both cell-extrinsic and
      intrinsic mechanisms often diminish the in-vivo potency of these therapeutic T
      cells, limiting their clinical efficacy and broader use. Direct activation of
      human T cells by Toll-like receptor (TLR) ligands induces T cell survival and
      proliferation, boosts the production of proinflammatory cytokines and augments
      resistance to regulatory T cell (Treg) suppression. Removal of the TLR ligand
      binding region results in constitutive signalling triggered by the remaining
      cytosolic Toll/interleukin-1 receptor (TIR) domain. The use of such TIR domains
      therefore offers an ideal means for equipping anti-tumour T cells with the
      arsenal of functional attributes required for improving current clinical
      protocols. Here we show that constitutively active (ca)TLR-4 can be expressed
      efficiently in human T cells using mRNA electroporation. The mere expression of
      caTLR-4 mRNA in polyclonal CD8 and CD4 T cells induced the production of
      interferon (IFN)-gamma, triggered the surface expression of CD25, CD69 and 4-1BB
      and up-regulated a panel of cytokines and chemokines. In tumour-infiltrating
      lymphocytes prepared from melanoma patients, caTLR-4 induced robust IFN-gamma
      secretion in all samples tested. Furthermore, caTLR-4 enhanced the anti-melanoma
      cytolytic activity of tumour-infiltrating lymphocytes and augmented the secretion
      of IFN-gamma, tumour necrosis factor (TNF)-alpha and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) for at least 4 days post-transfection. Our
      results demonstrate that caTLR-4 is capable of exerting multiple T cell-enhancing
      effects and can potentially be used as a genetic adjuvant in adoptive cell
      therapy.

PMID- 26212051
TI  - Concurrent Infection With Dengue Type 4 and Plasmodium falciparum Acquired in
      Haiti.
AB  - We report one laboratory-confirmed coinfection by dengue type 4 and Plasmodium
      falciparum imported to Spain from Haiti. Diagnosis was made by real-time
      polymerase chain reaction (RT-PCR), serology, quantitative buffy coat, and thick
      blood smear. In areas where both infections are present, diagnosis of both
      diseases should be considered because a delay in the treatment of malaria could
      be fatal. 

PMID- 26212052
TI  - Premature Aging in Fibromyalgia.
AB  - Chronic pain is highly prevalent in older adults, and until recently, was
      considered to be common but relatively "benign." Mounting evidence, however,
      suggests that some of the 116 million US adults who suffer from chronic pain are
      also at an increased risk for developing age-related diseases prematurely,
      suffering earlier cognitive and physical decline, and experiencing earlier
      mortality. Given the aging US population and the prevalence of chronic pain along
      with related healthcare consequences, there is a critical need to better
      understand the relationship between aging and chronic pain. Herein, we focus on
      one chronic pain state, fibromyalgia, and provide an overview of the evidence
      suggesting that individuals with this chronic pain condition show signs of
      premature aging. 

PMID- 26212054
TI  - Inflamm-ageing and Senescence in Gout: The Tale of an Old King's Disease.
AB  - Gout is the most common auto-inflammatory arthritis that leads to severe
      comorbidities such as cardiovascular diseases, renal impairment and metabolic
      disorders at an early age. We hypothesize that chronic as well as frequent flares
      of intermittent inflammation, caused by uric acid contribute to an early onset of
      cardiovascular-, renal- and metabolic diseases. Persistent exposure of the cells
      to such inflammatory events elaborates DNA damage, excessive cell turnover
      inconsistent with age and telomere shortening which is representative for
      accelerated senescence. In this review we aim to untangle the intriguing effect
      of inflammation-induced cellular senescence on the high prevalence of age-related
      cardiovascular, renal and metabolic diseases in gout. 

PMID- 26212053
TI  - Aging and Immunopathology in Primary Sjogren's Syndrome.
AB  - Sicca complaints (sensation of dry mouth and/or eyes) are present in about a
      quarter of the individuals above the age of 65 years old and are mainly due to
      medication. However, physiological changes that occur during aging might also
      lead to a diminished glandular function. These age-related changes are, at least
      in part, to be the consequence of decreased androgen levels. In addition to these
      physiological effects that occur during normal aging, sicca complaints can also
      be caused by Sjogren's syndrome (SS): a systemic auto-inflammatory disorder
      mainly affecting exocrine glands. Genetic factors, lowered levels of gonadal
      hormones and (viral) infections appear to contribute to the etiology of the
      syndrome. The incidence of SS is higher among aged individuals, which might be
      due to earlier diagnosis, as the onset of SS in an individual with age-related
      exocrine gland dysfunction lowers the threshold for sicca complaints. On the
      other hand, physiological aging might be considered as a risk factor for
      development of SS, resulting in a faster development of the syndrome.
      Differentiating physiological sicca complaints from SS in the elderly can be
      challenging, since apparently healthy individuals might present with auto
      antibodies and lymphocytic infiltrates in salivary glands might be present as
      well. The drop in the level of androgens and estrogens upon aging,
      immunosenescence and pro-inflammatory features of the aging immune system may all
      contribute to the etiology of pSS in the elderly. In this review, we describe the
      physiological effects of aging and the influence of SS on exocrine gland
      morphology and function. 

PMID- 26212055
TI  - Aging and Systemic Lupus Erythematosus - Immunosenescence and Beyond.
AB  - The lifespan of humans has increased drastically over the last decades;
      considerable effort has been applied to delineate the mechanisms behind aging in
      order to find strategies for longevity. As the benefits of the gained knowledge
      might extend to diseases, where accelerated aging is suspected, the role of aging
      in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) is of
      particular interest. In this review the immunological similarities of SLE and
      aging are analyzed on three levels: the clinical, the cellular and the molecular,
      in order to find possible common pathological mechanisms. Common clinical
      features (e.g. increased infection rates, incidence of tumors and cardiovascular
      diseases) of SLE-patients and elderly individuals and shared characteristics of
      immuno-senescence and SLE are identified. These similarities are strongest in the
      adaptive immune system, where terminally differentiated T-cells and an
      immunological risk profile are found in both conditions. Also the aging innate
      immune system has overlapping features with SLE, exemplified by a generally
      lowered phagocytic capacity. However, great disparities between the aging immune
      system and SLE become apparent on a closer look, affecting numbers, phenotype and
      function of most immune cells, ranging from NETosis by granulocytes to the
      mechanisms underlying abnormal IL-2 production by T-cells. On the molecular
      level, also the increased presence of aging mechanisms like telomere attrition,
      DNA damage, autophagy and the characteristics of the mTOR pathway in SLE,
      possibly contributing to the shared changes on the cellular and clinical level
      are elaborated. The possible implications thereof concern existing
      (hydroxychloroquine, rapamycine, Glucocorticoids) as well as novel therapeutic
      strategies targeting more specific pathways which might rapidly reach the
      clinical arena. Overall a differential view on the similarities of aging and SLE
      and possible consequences is presented. 

PMID- 26212056
TI  - Cellular Aging, Senescence and Autophagy Processes in Osteoarthritis.
AB  - Osteoarthritis (OA) is the most common form of arthritis and a huge health and
      financial burden. The prevalence and incidence of OA are likely to rise due to
      increasing life expectancy. Although the link between aging and OA is well
      established, little is known about the mechanisms by which aging contributes to
      OA development. In recent years, progress has been made in understanding the
      molecular mechanisms of chondrocyte aging and senescence. Aging and senescent
      chondrocytes display a senescence-associated secretory phenotype (SASP)
      associated with increased secretion of pro-inflammatory mediators, extracellular
      matrix degrading enzymes and oxidative stress, all of which can contribute to the
      development and progression of OA. There is also evidence that autophagy, an
      essential homeostatic process, declines with aging and during OA. This review
      will focus on our current understanding of chondrocyte aging, senescence, and
      autophagy and their potential roles in the development and progression of OA. An
      understanding of these processes would be very useful in devising strategies to
      treat OA or to delay its development. 

PMID- 26212059
TI  - Early Term versus Term Delivery in the Management of Fetal Growth Restriction: A
      Comparison of Two Protocols (Podcast).

PMID- 26212058
TI  - Biological Ageing, Inflammation and Nutrition: How Might They Impact on Systemic
      Sclerosis?
AB  - The number of aged individuals within the global population is increasing, which
      foreshadows a major societal and global health challenge. By 2050 those over 65
      years old will outnumber children under 15 years of age. This situation will
      bring with it multifarious variations in health and functional status, occurring
      with increasing age and which remain incompletely understood. Ageing, however, is
      not solely a passive degenerative process but one that is actively regulated by
      distinct molecular pathways. Understanding this molecular basis of ageing is an
      essential step for therapeutic manipulation to combat age-related disease.
      Diseases such as SSc, RA and SLE may share common age related pathways of early
      dysregulation with other diseases of ageing, such that the biomarkers and
      interventions applied to prevent late stage disease will also tackle common
      fundamental pathways of ageing processes. This chapter will seek to explore and
      discuss the possible influence of these factors and their impact on disease
      processes, with specific reference to SSc in the context of it being a disease of
      ageing. It will address the contribution of socioeconomic, psychosocial and
      nutritional confounders of health span through the life course. In particular, it
      will seek to contextualize the development of inflammatory burden and allostatic
      overload and their contribution to morbidity and mortality. Importantly, this
      chapter will provide a context for transgenerational and other epigenetic
      effects, which are emerging as contributory components in disease susceptibility
      and progression. 

PMID- 26212060
TI  - Neonatal Biomarkers of Inflammation: Correlates of Early Neurodevelopment and
      Gait in Very-Low-Birth-Weight Preterm Children.
AB  - OBJECTIVE: Neonatal biomarkers of inflammation were examined in relation to early
      neurodevelopment and gait in very-low-birth-weight (VLBW) preterm children. We
      hypothesized that preterm infants exposed to higher levels of neonatal
      inflammation would demonstrate lower scores on Bayley Scales of Infant Toddler
      Development, 3rd ed. (BSID-III) and slower gait velocity at 18 to 22 months
      adjusted age. STUDY DESIGN: A total of 102 VLBW preterm infants (birthweight [BW]
      <= 1,500 g, gestational age [GA] <= 32 weeks) admitted to neonatal intensive care
      unit [NICU] were recruited. Neonatal risk factors examined were GA at birth, BW,
      bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of
      prematurity, sepsis, and serum C-reactive protein (CRP), albumin, and total
      bilirubin over first 2 postnatal weeks. At 18 to 22 months, neurodevelopment was
      assessed with BSID-III and gait was assessed with an instrumented mat. RESULTS:
      Children with neonatal CRP >= 0.20 mg/dL (n = 52) versus < 0.20 mg/dL (n = 37)
      had significantly lower BSID-III composite cognitive (92.0 +/- 13.1 vs. 100.1 +/-
      9.6, p = 0.002), language (83.9 +/- 16.0 vs. 95.8 +/- 14.2, p < 0.001), and motor
      scores (90.0 +/- 13.2 vs. 98.8 +/- 10.1, p = 0.002), and slower gait velocity
      (84.9 +/- 19.0 vs. 98.0 +/- 22.4 cm/s, p = 0.004). Higher neonatal CRP correlated
      with lower cognitive (rho =  - 0.327, p = 0.002), language (rho =  - 0.285, p =
      0.007), and motor scores (rho =  - 0.257, p = 0.015), and slower gait (rho =  -
      0.298, p = 0.008). Multivariate analysis demonstrated neonatal CRP >= 0.20 mg/dL
      significantly predicted BSID-III cognitive (adjusted R(2) = 0.104, p = 0.008),
      language (adjusted R(2) = 0.124, p = 0.001), and motor scores (adjusted R(2) =
      0.122, p = 0.004). CONCLUSIONS: Associations between low-level neonatal
      inflammation and neurodevelopment suggest early biomarkers that may inform
      neuroprotective treatment for preterm children.

PMID- 26212057
TI  - Rheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging.
AB  - Age is the most important risk factor for the development of infectious diseases,
      cancer and chronic inflammatory diseases including rheumatoid arthritis (RA). The
      very act of living causes damage to cells. A network of molecular, cellular and
      physiological maintenance and repair systems creates a buffering capacity against
      these damages. Aging leads to progressive shrinkage of the buffering capacity and
      increases vulnerability. In order to better understand the complex mammalian
      aging processes, nine hallmarks of aging and their interrelatedness were recently
      put forward. RA is a chronic autoimmune disease affecting the joints. Although RA
      may develop at a young age, the incidence of RA increases with age. It has been
      suggested that RA may develop as a consequence of premature aging
      (immunosenescence) of the immune system. Alternatively, premature aging may be
      the consequence of the inflammatory state in RA. In an effort to answer this
      chicken and egg conundrum, we here outline and discuss the nine hallmarks of
      aging, their contribution to the pre-aged phenotype and the effects of treatment
      on the reversibility of immunosenescence in RA. 

PMID- 26212062
TI  - Early intervention in pertussis outbreak with high attack rate in cohort of
      adolescents with complete acellular pertussis vaccination in Valencia, Spain,
      April to May 2015.
AB  - Forty-three pertussis cases reported in May 2015 in Valencia were linked to a
      school outbreak where 90% of the students had been vaccinated. Cases were
      diagnosed upon paediatrician consultation and in hospital emergency units.
      Approximately half of the cases were students born in 2002, the first age cohort
      with complete shift to acellular pertussis vaccine. Public health intervention,
      visiting school premises to conduct interviews, sample collection and early
      antibiotic prophylaxis stopped further spread in the community.

PMID- 26212061
TI  - Calcium ion-induced formation of beta-sheet/-turn structure leading to alteration
      of osteogenic activity of bone morphogenetic protein-2.
AB  - Preserving bioactivity of bone morphogenetic protein 2 (BMP-2) still remains a
      challenge in protein-based therapy. It is not known how Ca(2+) released from
      extracellular matrix or existing in physiological environment influences
      bioactivity in situ till now. Here, effects of extracellular Ca(2+) on
      conformation and osteogenic bioactivity of recombinant human BMP-2 (rhBMP-2) were
      investigated systematically. In vitro results indicated that Ca(2+) could bind
      rhBMP-2 rapidly and had no obvious effect on cell behaviors. Low concentration of
      Ca(2+) (0.18 mM) enhanced rhBMP-2-induced osteogenic differentiation, while high
      Ca(2+) concentration (>1.80 mM) exerted negative effect. In vivo ectopic bone
      formation exhibited similar trend. Further studies by circular dichroism
      spectroscopy, fluorescence spectroscopy, together with cell culture experiments
      revealed at low concentration, weak interaction of Ca(2+) and rhBMP(-)2 slightly
      increased beta-sheet/-turn content and facilitated recognition of BMP-2 and
      BMPRIA. But, high Ca(2+) concentration (>1.8 mM) induced formation of Ca-rhBMP-2
      complex and markedly increased content of beta-sheet/-turn, which led to
      inhibition binding of rhBMP-2 and BMPRIA and thus suppression of downstream
      Smad1/5/8, ERK1/2 and p38 mitogen-associated protein kinase signaling pathways.
      Our work suggests osteogenic bioactivity of BMP-2 can be adjusted via
      extracellular Ca(2+), which should provide guide and assist for development of
      BMP-2-based materials for bone regeneration. 

PMID- 26212063
TI  - Assessing the risk of observing multiple generations of Middle East respiratory
      syndrome (MERS) cases given an imported case.
AB  - To guide risk assessment, expected numbers of cases and generations were
      estimated, assuming a case importation of Middle East respiratory syndrome
      (MERS). Our analysis of 36 importation events yielded the risk of observing
      secondary transmission events at 22.7% (95% confidence interval: 19.3-25.1). The
      risks of observing generations 2, 3 and 4 were estimated at 10.5%, 6.1% and 3.9%,
      respectively. Countries at risk should be ready for highly variable outcomes
      following an importation of MERS.

PMID- 26212065
TI  - Authors correction for Euro Surveill. 2015;20(25).
AB  - In the article 'Event-based surveillance of food- and waterborne diseases in
      Europe: 'urgent inquiries' (outbreak alerts) during 2008 to 2013' by C. M.
      Gossner et al., published on 25 June 2015, two members of the European Food and
      Waterborne Diseases Study Group from Bulgaria were inadvertently omitted. They
      were added on 8 July 2015, on request of the authors.

PMID- 26212064
TI  - National point prevalence survey of healthcare-associated infections and
      antimicrobial use in French home care settings, May to June 2012.
AB  - In May and June 2012, a national point prevalence survey (PPS) of healthcare
      associated infections (HAIs) and antimicrobial use was conducted among French
      patients under home-based hospital care (HBHC). Data from 5,954 patients in 179
      volunteer HBHC providers were collected. Prevalence of patients with at least one
      active HAI was 6.8% (95% confidence interval (CI): 6.1-7.4). Prevalence of those
      receiving at least one antimicrobial agent was 15.2% (95% CI: 14.3-16.1). More
      than a third (35.5%) of HAIs were HBHC-associated, 56% were imported from a
      healthcare facility and 8.5% of indeterminate origin. The main infection sites
      were urinary tract (26.6%), skin and soft tissue (17.6%), surgical site (15%),
      and pneumonia or other respiratory tract infections (13.5%). In multivariate
      analysis, three risk factors were associated with HBHC-associated infections:
      urinary catheter, at least one vascular catheter and a McCabe score 1 or 2. The
      most frequently isolated microorganism was Staphylococcus aureus (20.7%), 28.1%
      of them meticillin-resistant. Non-susceptibility to third-generation
      cephalosporins was reported in 25.3% of Enterobacteriaceae, of which 16.1% were
      extended spectrum beta-lactamase-producing strains. The most prescribed
      antimicrobials were fluoroquinolones (16.1%), and third-generation cephalosporins
      (14.5%). PPS may be a good start in HBHC to obtain information on epidemiology of
      HAIs and antimicrobial use.

PMID- 26212066
TI  - Erratum for Euro Surveill. 2015;20(16).
AB  - In the article 'Changing hepatitis A epidemiology in the European Union: new
      challenges and opportunities' by C M Gossner et al., published on 23 April 2015,
      the following sentence "Self-controls by the industries and official controls by
      the food safety authorities Regulatory controls and industry auto-controls are
      unlikely to completely prevent the importation of HAV-contaminated foods from
      highly endemic countries into the EU/EEA." was corrected to read "Self-controls
      by the industries and official controls by the food safety authorities are
      unlikely to completely prevent the importation of HAV-contaminated foods from
      highly endemic countries into the EU/EEA." The correction was made on 7 July
      2015.

PMID- 26212067
TI  - Magnetic-Field-Assisted Fabrication and Manipulation of Nonspherical Polymer
      Particles in Ferrofluid-Based Droplet Microfluidics.
AB  - We report a novel magnetic-field-assisted method for the fabrication and
      manipulation of nonspherical polymer particles within a ferrofluid-based droplet
      microfluidic device. Shape control and chain assembly of droplets with tunable
      lengths have been achieved. 

PMID- 26212068
TI  - Hepatocellular carcinoma treatment over sorafenib: epigenetics, microRNAs and
      microenvironment. Is there a light at the end of the tunnel?
AB  - INTRODUCTION: Sorafenib is currently the only approved therapy in hepatocellular
      carcinoma (HCC). Alternative first- and second-line treatments are a significant
      unmet medical need, and several biologic agents have been tested in recent years,
      with poor results. Therefore, angiogenic pathways and the cytokine cascade remain
      possible targets in HCC. Recent studies suggest a role of epigenetic processes,
      associated with the initiation and development of HCC. In this field, DNA
      methylation, micro-RNAs (miRNAs) and tumor microenvironment cells became a
      possible new target for HCC treatment. AREAS COVERED: This review explains the
      possible role of DNA methylation and histone deacetylase inhibitors as predictive
      biomarkers and target therapy, the extensive world of the promising miRNA
      blockade strategy, and the recent strong evidence of correlation between HCC
      tumors and peritumoral stroma cells. The literature and preclinic/clinic data
      were obtained through an electronic search. EXPERT OPINION: Future research
      should aim to understand how best to identify patient groups that would benefit
      most from the prescribed therapy. To overcome the 'therapeutic stranding' of HCC,
      a possible way out from the current therapeutic tunnel might be to evaluate the
      major epigenetic and genetic processes involved in HCC carcinogenesis, not
      underestimating the tumor microenvironment and its 'actors' (angiogenesis, immune
      system, platelets). We are only at the start of a long journey towards the
      elucidation of HCC molecular pathways as therapeutic targets. Yet, currently this
      path appears to be the only one to cast some light at the end of the tunnel.

PMID- 26212069
TI  - Thrombosis in Lymphoma Patients and in Myeloma Patients.
AB  - The risk of venous thromboembolism (VTE) in patients with cancer is several-fold
      higher than that in individuals without cancer. Recent studies demonstrated a
      high incidence of VTE in patients with hematologic malignancies as well as in
      patients with solid cancers. The reported incidence of VTE in lymphoma is
      variable, ranging from less than 5% to 59.5%. The incidence of VTE is higher in
      non-Hodgkin lymphoma than it is in Hodgkin lymphoma. The incidence of VTE also
      varies according to the disease grade, the disease stage, the performance status
      of the patient, and the site of disease. Most VTE cases occur at the diagnosis of
      cancer or early in the course of cancer treatment. An elevated incidence of VTE
      is also reported in cases of myeloma. VTE occurs in approximately 5% of myeloma
      patients treated with conventional chemotherapy, and treatment of myeloma
      patients with immunomodulatory drugs (IMid)-based therapy increases the risk of
      VTE. Prophylactic aspirin or anticoagulant is used in myeloma patients treated
      with IMid-based therapy. Several reports have indicated that the incidence of VTE
      is relatively low in Asian patients treated with IMid-based therapy, and
      concomitant use of bortezomib reduces the risk of VTE. The incidence of arterial
      thrombosis is also increased in patients with myeloma and monoclonal gammopathy
      of undetermined significance. Further studies are needed to develop a predictive
      model for identifying patients with lymphoma and myeloma who are at high risk for
      developing thrombosis. 

PMID- 26212071
TI  - p53 activity contributes to defective interfollicular epidermal differentiation
      in hyperproliferative murine skin.

PMID- 26212072
TI  - Use of permanent hair dyes and risk of vitiligo in women.

PMID- 26212073
TI  - Selective transport between heterogeneous hyphal compartments via the plasma
      membrane lining septal walls of Aspergillus niger.
AB  - Hyphae of ascomycetes are compartmentalized by septa. The central pore in these
      septa allows for cytoplasmic streaming. However, many of these pores are closed
      by Woronin bodies in Aspergillus, which prevents cytoplasmic mixing and thus
      maintains hyphal heterogeneity. Here, glucose uptake and transport was studied in
      Aspergillus niger. Glucose uptake was higher in the hyphal population with high
      transcriptional activity when compared to the population with low transcriptional
      activity. Glucose was transported from the colony center to the periphery, but
      not vice versa. This unidirectional flow was similar in the wild-type and the
      DeltahexA strain that does not form Woronin bodies. This indicated that septal
      plugging by Woronin bodies does not impact long distance glucose transport.
      Indeed, the glucose analogue 2-NBDG (2-(N-[7-nitrobenz-2-oxa-1,3-diazol-4
      yl]amino)-2-deoxyglucose) translocated to neighboring hyphal compartments despite
      Woronin body mediated plugging of the septum that separated these compartments.
      Notably, 2-NBDG accumulated in septal cross walls, indicating that
      intercompartmental glucose transport is mediated by transporters that reside in
      the plasma membrane lining the septal cross-wall. The presence of such
      transporters would thus enable selective transport between heterogeneous
      compartments. 

PMID- 26212070
TI  - Corresponding ECoG and fMRI category-selective signals in human ventral temporal
      cortex.
AB  - Functional magnetic resonance imaging (fMRI) and electrocorticography (ECoG)
      research have been influential in revealing the functional characteristics of
      category-selective responses in human ventral temporal cortex (VTC). One
      important, but unanswered, question is how these two types of measurements might
      be related with respect to the VTC. Here we examined which components of the ECoG
      signal correspond to the fMRI response by using a rare opportunity to measure
      both fMRI and ECoG responses from the same individuals to images of exemplars of
      various categories including faces, limbs, cars and houses. Our data reveal three
      key findings. First, we discovered that the coupling between fMRI and ECoG
      responses is frequency and time dependent. The strongest and most sustained
      correlation is observed between fMRI and high frequency broadband (HFB) ECoG
      responses (30-160 hz). In contrast, the correlation between fMRI and ECoG signals
      in lower frequency bands is temporally transient, where the correlation is
      initially positive, but then tapers off or becomes negative. Second, we find that
      the strong and positive correlation between fMRI and ECoG signals in all
      frequency bands emerges rapidly around 100 ms after stimulus onset, together with
      the onset of the first stimulus-driven neural signals in VTC. Third, we find that
      the spatial topology and representational structure of category-selectivity in
      VTC reflected in ECoG HFB responses mirrors the topology and structure observed
      with fMRI. These findings of a strong and rapid coupling between fMRI and HFB
      responses validate fMRI measurements of functional selectivity with recordings of
      direct neural activity and suggest that fMRI category-selective signals in VTC
      are associated with feed-forward neural processing.

PMID- 26212074
TI  - The phenotype of a phospholipase C (plc-1) mutant in a filamentous fungus,
      Neurospora crassa.
AB  - In the filamentous fungus Neurospora crassa, phospholipase C may play a role in
      hyphal extension at the growing tips as part of a growth-sensing mechanism that
      activates calcium release from internal stores to mediate continued expansion of
      the hyphal tip. One candidate for a tip-localized phospholipase C is PLC-1. We
      characterized morphology and growth characteristics of a knockout mutant (KO plc
      1) and a RIP mutated strain (RIP plc-1) (missense mutations and a nonsense
      mutation render the gene product non-functional). Growth and hyphal cytology of
      wildtype and KO plc-1 were similar, but the RIP plc-1 mutant grew slower and
      exhibited abnormal membrane structures at the hyphal tip, imaged using the
      fluorescence dye FM4-64. To test for causes of the slower growth of the RIP plc-1
      mutant, we examined its physiological poise compared to wildtype and the KO plc-1
      mutant. The electrical properties of all three strains and the electrogenic
      contribution of the plasma membrane H(+)-ATPase (identified by cyanide
      inhibition) were the same. Responses to high osmolarity were also similar.
      However, the RIP plc-1 mutant had a significantly lower turgor, a possible cause
      of its slower growth. While growth of all three strains was inhibited by the
      phospholipase C inhibitor 3-nitrocoumarin, the RIP plc-1 mutant did not exhibit
      hyphal bursting after addition of the inhibitor, observed in both wildtype and
      the KO plc-1 mutant. Although the plc-1 gene is not obligatory for tip growth,
      the phenotype of the RIP plc-1 mutant - abnormal tip cytology, lower turgor and
      resistance to inhibitor-induced hyphal bursting - suggest it does play a role in
      tip growth. The expression of a dysfunctional plc-1 gene may cause a shift to
      alternative mechanism(s) of growth sensing in hyphal extension. 

PMID- 26212075
TI  - Chemokine (C-X-C motif) ligand 11 levels predict survival in cirrhotic patients
      with transjugular intrahepatic portosystemic shunt.
AB  - BACKGROUND & AIMS: Chemokines, such as CXCR3-ligands, have been identified to
      play an important role during hepatic injury, inflammation and fibrosis. While
      CXCL9 is associated with survival in patients receiving transjugular intrahepatic
      portosystemic shunt (TIPS), the role of CXCL11 in severe portal hypertension
      remains unknown. METHODS: CXCL11-levels were measured in 136 patients with liver
      diseases, and 63 healthy controls. In further 47 cirrhotic patients receiving
      TIPS, CXCL11 levels were measured in portal and hepatic veins at TIPS insertion
      by cytometric bead array. CXCL11-levels were measured in 23 patients in cubital
      vein and right atrium, whereas in 24 patients in portal and hepatic blood at an
      invasive reevaluation. RESULTS: CXCL11-levels were increased with the severity of
      liver fibrosis. CXCL11-levels from portal, hepatic and cubital veins and right
      atrium showed a highly significant correlation among each other in these
      patients. Furthermore, levels of CXCL11 from the right atrium were significantly
      higher than those from cubital vein. Interestingly, patients with alcoholic
      cirrhosis had significantly lower CXCL11-levels, than other aetiologies of
      cirrhosis. After TIPS, CXCL11 levels correlated with the degree of portal
      pressure and patients with higher CXCL11-levels in portal and hepatic veins
      showed higher mortality. Multivariate analysis revealed hepatic CXCL11-levels
      before TIPS, creatinine and age as independent predictors for survival in TIPS
      patients, whereas MELD score and low portal CXCL11-levels after TIPS predicted
      long-term survival. CONCLUSION: CXCL11 levels are mainly increased in patients
      with non-alcoholic cirrhosis and high portal pressure. Moreover, levels of CXCL11
      might predict long-time survival of cirrhotic patients bearing TIPS.

PMID- 26212076
TI  - Natural outcome of cannabis use disorder: a 3-year longitudinal follow-up.
AB  - AIMS: To assess the prevalence and correlates of remission from cannabis use
      disorders (CUDs), focusing on the proportion of individuals with CUDs that remit
      without abstaining from cannabis use. DESIGN: Three-year longitudinal study.
      SETTING: Wave 1 (2001) and wave 2 (2004) of the National Epidemiologic Survey on
      Alcohol and Related Conditions (NESARC), a nationally representative sample of US
      adults aged 18 years and over. PARTICIPANTS: Our sample included 444 individuals
      diagnosed with DSM-IV cannabis abuse and/or dependence during the 12 months prior
      to wave 1 of the NESARC. MEASUREMENTS: Baseline socio-demographic and clinical
      correlates were analysed for possible outcomes of CUDs after 3 years: abstinent
      remission, non-abstinent remission and sustained disorder. FINDINGS:
      Approximately two-thirds (67%) of individuals with baseline CUD remitted at
      follow-up. Approximately 37% of those who remitted were non-abstinent. Remission
      was associated with Hispanic ethnicity [odds ratio (OR)=2.59; 95% confidence
      interval (CI)=1.27-4.87], baseline daily or almost daily use of cannabis
      (OR=1.91; 95% CI=1.15-3.16), baseline use of other drugs (OR=1.63; 95% CI=1.04
      2.56) and two or more medical conditions at baseline (OR=8.40; 95% CI=2.67
      26.41). Non-abstinent remission was associated with baseline daily or almost
      daily use of cannabis (OR=1.92; 95% CI=1.05-3.51). CONCLUSIONS: A substantial
      level of remission from cannabis use disorders (CUDs), including non-abstinent
      remission, suggests that the nature of CUDs may be more unstable than reported
      previously.

PMID- 26212077
TI  - Psychological stress and adjustment in pregnancy following assisted reproductive
      technology and spontaneous conception: A systematic review.
AB  - The aim of this review was to examine studies describing the psychological stress
      and adjustment in pregnancy after an assisted reproductive technology (ART)
      treatment. A systematic search of the electronic databases was performed. This
      review considered only quantitative, primary studies in the English language,
      published during the period 2000-2014 and relevant to the objective. The
      population of interest was previously infertile pregnant women. Outcome variables
      were general anxiety, depressive symptoms, pregnancy-specific anxiety, quality of
      life, self-esteem, pregnancy attitudes and adjustment, and maternal-fetal
      attachment. Twenty studies met the inclusion and methodological criteria and were
      included in the review. The review revealed that compared to women who conceive
      naturally or to general norms, women who conceive after an in vitro fertilization
      treatment had greater pregnancy-specific anxiety, poorer quality of life, either
      the same or less depressive symptomatology, the same level of self-esteem, more
      positive attitudes toward pregnancy demands, and higher levels of maternal-fetal
      attachment. However, the evidence regarding the general anxiety levels in
      pregnancy after an ART treatment was inconclusive. Methodological limitations and
      differences across studies may explain the inconsistencies in their findings
      regarding the impact of ART. This review provides an insight into psychological
      reactions and adjustment in pregnancy after an ART treatment. 

PMID- 26212078
TI  - [What else? Sudden dyspnea in a 45-year-old woman].

PMID- 26212079
TI  - Functional Correction of Large Factor VIII Gene Chromosomal Inversions in
      Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9.
AB  - Hemophilia A is an X-linked genetic disorder caused by mutations in the F8 gene,
      which encodes the blood coagulation factor VIII. Almost half of all severe
      hemophilia A cases result from two gross (140-kbp or 600-kbp) chromosomal
      inversions that involve introns 1 and 22 of the F8 gene, respectively. We derived
      induced pluripotent stem cells (iPSCs) from patients with these inversion
      genotypes and used CRISPR-Cas9 nucleases to revert these chromosomal segments
      back to the WT situation. We isolated inversion-corrected iPSCs with frequencies
      of up to 6.7% without detectable off-target mutations based on whole-genome
      sequencing or targeted deep sequencing. Endothelial cells differentiated from
      corrected iPSCs expressed the F8 gene and functionally rescued factor VIII
      deficiency in an otherwise lethal mouse model of hemophilia. Our results
      therefore provide a proof of principle for functional correction of large
      chromosomal rearrangements in patient-derived iPSCs and suggest potential
      therapeutic applications.

PMID- 26212081
TI  - HIV vaccine: Can it be developed in the 21st century?
AB  - HIV infection is a major public health problem especially in the developing
      countries. Once a person infects with HIV, it remained infected for lifelong. The
      advanced stage developed after 10-15 y of HIV infection that stage is called
      acquired immunodeficiency syndrome (AIDS). From 1990 to 2000 the number of people
      living with HIV rose from 8 million to 27 million; since the beginning of the
      HIV/AIDS epidemic, AIDS has claimed almost 39million lives so far. Till now,
      there is no cure for HIV infection; however, after the introduction of effective
      treatment with antiretroviral (ARV) drugs the HIV individual can enjoy healthy
      and productive lives. Vaccine is safe and cost-effective to prevent illness,
      impairment, disability and death. Like other vaccines, a preventive HIV vaccine
      could help save millions of lives. All vaccines work the same way i.e. the
      antigen stimulate the immune system and develop antibodies. The ultimate goal is
      to develop a safe and effective vaccine that protects people worldwide from
      getting infected with HIV. However, some school of thought that vaccine may
      protects only some HIV people, it could have a major impact on the rates of
      transmission of HIV and this will help in control of epidemic, especially in
      populations where high rate of HIV transmission. In the past, some scientist
      doubted on the development of an effective polio vaccine, but now we are near to
      eradicate the polio from the world this is possible because of successful
      vaccination programmes. HIV vaccine research is aided by the not-for-profit
      International AIDS/HIV vaccine Initiative (IAVI), which helps to support and
      coordinate vaccine research, development, policy and advocacy around the world.
      Although the challenges for scientist are intimidating but scientists remain
      hopeful that they can develop safe and effective HIV vaccines for patients in
      future. 

PMID- 26212080
TI  - Tetraspanin 3 Is Required for the Development and Propagation of Acute
      Myelogenous Leukemia.
AB  - Acute Myelogenous Leukemia (AML) is an aggressive cancer that strikes both adults
      and children and is frequently resistant to therapy. Thus, identifying signals
      needed for AML propagation is a critical step toward developing new approaches
      for treating this disease. Here, we show that Tetraspanin 3 is a target of the
      RNA binding protein Musashi 2, which plays a key role in AML. We generated Tspan3
      knockout mice that were born without overt defects. However, Tspan3 deletion
      impaired leukemia stem cell self-renewal and disease propagation and markedly
      improved survival in mouse models of AML. Additionally, Tspan3 inhibition blocked
      growth of AML patient samples, suggesting that Tspan3 is also important in human
      disease. As part of the mechanism, we show that Tspan3 deficiency disabled
      responses to CXCL12/SDF-1 and led to defects in AML localization within the
      niche. These identify Tspan3 as an important regulator of aggressive leukemias
      and highlight a role for Tspan3 in oncogenesis. 

PMID- 26212082
TI  - The role of Delta-like 4 ligand/Notch-ephrin-B2 cascade in the pathogenesis of
      preeclampsia by regulating functions of endothelial progenitor cell.
AB  - INTRODUCTION: Preeclampsia is a hypertensive complication in pregnancy, closely
      related to endothelial dysfunction. Endothelial progenitor cells (EPCs) have the
      capacity for endothelial repair. Both Ephrin-B2 and Dll4/Notch pathway play
      critical roles in various steps of angiogenesis. In addition, there is an up
      regulation of ephrin-B2 expression consequent to Dll4/Notch activation in
      endothelial cells (ECs). However, the roles of ephrin-B2 and Dll4/Notch signaling
      on EPCs, as well as the relationship between them, have not been completely
      characterized. METHODS: We analyzed expression of ephrin-B2 in the EPCs and
      placenta from preeclampsia and normal pregnancy. Then up-regulation and down
      regulation strategies were employed to detect the effects of ephrin-B2 on EPC
      proliferation, differentiation, migration and HUVEC-tube formation. The effects
      of Dll4/Notch signaling on EPCs' functions were determined by repeating the
      assays in the presence of Dll4 or DAPT as agonists or antagonists of Notch
      signaling, respectively. RESULTS: Ephrin-B2 expression increased notably in
      preeclampsia EPCs and placenta, compared with controls. Up-regulation of ephrin
      B2 impaired EPCs' proliferation, differentiation, migration and HUVEC-tube
      formation capabilities. In contrast, down-regulation of ephrin-B2 in EPCs,
      resulted in the opposite effects. In addition, activation of Dll4/Notch signaling
      led to increased expression of ephrin-B2 and subsequent inhibition of EPCs
      activity. DISCUSSION: Ephrin-B2, a downstream of Dll4/Notch signaling pathway,
      might be act as an inhibitor of EPC-mediated vasculogenesis in vitro, as well as
      a potential target in the effort to promote angiogenesis of patients with
      preeclampsia.

PMID- 26212083
TI  - Creation of plastinated placentas as a novel teaching resource for medical
      education in obstetrics and gynaecology.
AB  - INTRODUCTION: Knowledge of the gross anatomy of the placenta is fundamental in
      order to help identify potential complications during pregnancy. The placenta is
      difficult to study without a three-dimensional appreciation of its structure. The
      aim of this study was to develop a collection of plastinated placenta specimens
      and accompanying clinical educational materials to provide learning resources for
      placental abnormalities and their associated pregnancy outcomes. These
      plastinates and educational modules were used as teaching resources for both
      undergraduate and post-graduate medical trainees in Obstetrics and Gynaecology.
      METHODS: Placentas were plastinated by S10 silicone plastination. Clinical
      education materials were created that included ultrasound images, photographs and
      information on the associated pregnancy outcomes. Utility of the plastinates was
      assessed using questionnaires completed by 70 medical students and 33 attendees
      at the 8th and 9th Annual International Human Placenta Workshop held at Queen's
      University, Kingston, ON. Attendees included graduate students, post-doctoral
      fellows, medical residents, research investigators and clinicians. RESULTS: Data
      collected demonstrated that 76.7% of medical student (n = 60) and 78.1% of
      Placenta Workshop attendees (n = 32) preferred plastinates as a supplemental
      learning resource compared to textbooks and images alone (36.7% and 37.5%
      respectively). All respondents also expressed the desire to have plastinated
      placentas available for future learning opportunities. DISCUSSION: Plastinated
      placentas are a valuable addition as teaching resources for many demographic
      groups with an interest in placental anatomy and pathology. Medical trainees and
      residents in Obstetrics and Gynaecology would benefit from the availability of
      plastinates as educational tools.

PMID- 26212084
TI  - Tight junction CLDN2 gene is a direct target of the vitamin D receptor.
AB  - The breakdown of the intestinal barrier is a common manifestation of many
      diseases. Recent evidence suggests that vitamin D and its receptor VDR may
      regulate intestinal barrier function. Claudin-2 is a tight junction protein that
      mediates paracellular water transport in intestinal epithelia, rendering them
      "leaky". Using whole body VDR(-/-) mice, intestinal epithelial VDR conditional
      knockout (VDR(DeltaIEC)) mice, and cultured human intestinal epithelial cells, we
      demonstrate here that the CLDN2 gene is a direct target of the transcription
      factor VDR. The Caudal-Related Homeobox (Cdx) protein family is a group of the
      transcription factor proteins which bind to DNA to regulate the expression of
      genes. Our data showed that VDR-enhances Claudin-2 promoter activity in a Cdx1
      binding site-dependent manner. We further identify a functional vitamin D
      response element (VDRE) 5?-AGATAACAAAGGTCA-3? in the Cdx1 site of the Claudin-2
      promoter. It is a VDRE required for the regulation of Claudin-2 by vitamin D.
      Absence of VDR decreased Claudin-2 expression by abolishing VDR/promoter binding.
      In vivo, VDR deletion in intestinal epithelial cells led to significant decreased
      Claudin-2 in VDR(-/-) and VDR(DeltaIEC) mice. The current study reveals an
      important and novel mechanism for VDR by regulation of epithelial barriers. 

PMID- 26212085
TI  - Does Enzymatic Hydrolysis of Glycosidically Bound Volatile Compounds Really
      Contribute to the Formation of Volatile Compounds During the Oolong Tea
      Manufacturing Process?
AB  - It was generally thought that aroma of oolong tea resulted from hydrolysis of
      glycosidically bound volatiles (GBVs). In this study, most GBVs showed no
      reduction during the oolong tea manufacturing process. beta-Glycosidases either
      at protein or gene level were not activated during the manufacturing process.
      Subcellular localization of beta-primeverosidase provided evidence that beta
      primeverosidase was located in the leaf cell wall. The cell wall remained intact
      during the enzyme-active manufacturing process. After the leaf cell disruption,
      GBV content was reduced. These findings reveal that, during the enzyme-active
      process of oolong tea, nondisruption of the leaf cell walls resulted in
      impossibility of interaction of GBVs and beta-glycosidases. Indole, jasmine
      lactone, and trans-nerolidol were characteristic volatiles produced from the
      manufacturing process. Interestingly, the contents of the three volatiles was
      reduced after the leaf cell disruption, suggesting that mechanical damage with
      the cell disruption, which is similar to black tea manufacturing, did not induce
      accumulation of the three volatiles. In addition, 11 volatiles with flavor
      dilution factor >=4(4) were identified as relatively potent odorants in the
      oolong tea. These results suggest that enzymatic hydrolysis of GBVs was not
      involved in the formation of volatiles of oolong tea, and some characteristic
      volatiles with potent odorants were produced from the manufacturing process. 

PMID- 26212087
TI  - Evaluation of oxide ceramics as anodes for SOECs.
AB  - La2NiO(4+delta) is characterised as an example for a potential anode material for
      high-temperature solid oxide electrolyser cells (SOECs). Short-term
      characterisation is performed from 700  degrees C to 850  degrees C between 0.01
      and 1 bar oxygen partial pressure (pO2) on asymmetrical cells using
      Ce(0.9)Gd(0.1)O(2-delta) as the electrolyte. Long-term degradation studies over
      more than 3000 hours are conducted at 800  degrees C and 0.2 bar pO2 in dry and
      humid atmospheres with and without a Cr-source placed in close vicinity to the
      cell. The SOEC anode performance is investigated by current-voltage curves
      combined with impedance spectroscopy. Current densities of up to -410 mA cm(-2)
      are applied in current-voltage measurements and during long-term degradation
      studies. A total increase in anode resistance by 350% is observed over the course
      of the degradation measurements in an increasingly harsh environment. Post-test
      analyses by SEM/EDX on a polished cross section of the cell show the presence of
      several contaminants in the electrode structure. However, chromium has not been
      identified by EDX even after prolonged exposure to Cr-sources in humid
      atmospheres, which is attributed to the anodic polarisation of the electrode.
      Electrode delamination appears to be the main factor for the strong loss in
      performance.

PMID- 26212086
TI  - Laser-scanning cytometry can quantify human adipocyte browning and proves
      effectiveness of irisin.
AB  - Laser-scanning cytometry is presented as a tool allowing population scale
      analysis of ex vivo human brown adipogenic differentiation. It combines texture
      analysis and detection of Ucp1 protein content in single brown adipocytes of
      mixed cell populations with gene expression pattern and functional
      characteristics of browning. Using this method we could validate mouse data in
      human samples demonstrating the effectiveness of irisin to induce "beige"
      differentiation of subcutaneous white adipocytes. 

PMID- 26212088
TI  - Cognitive flexibility mediates the relation between intolerance of uncertainty
      and safety signal responding in those with panic disorder.
AB  - There is a growing literature associating anxiety disorders with an inability to
      inhibit defensive responding during safety conditions of threatening tasks.
      However, investigations on the relation between panic disorder (PD) and defensive
      responding to safety have yielded mixed results. A recent study from our
      laboratory revealed that intolerance of uncertainty (IU) moderates this
      association, such that only individuals with PD and a high IU exhibit heightened
      startle potentiation during safety. The mechanism underlying this relationship is
      unknown. Given that safety conditions typically alternate with periods of threat,
      cognitive flexibility (i.e., the ability to adjust one's habitual responding to a
      situation, given the input of new information) may be involved in the ongoing
      reappraisal of danger and adjustment of defensive responding. Thus, the present
      study sought to investigate whether deficits in cognitive flexibility mediate the
      association between IU and defensive responding to safety among a sample of 71
      adults diagnosed with PD. As hypothesised, cognitive flexibility mediated the
      relationship between IU and heightened startle potentiation during safety
      conditions. This finding suggests that within this subgroup, a failure to inhibit
      defensive responding during safety conditions may be due to deficits in cognitive
      flexibility.

PMID- 26212089
TI  - Small intestinal bacterial overgrowth and toll-like receptor signaling in
      patients with non-alcoholic fatty liver disease.
AB  - BACKGROUND AND AIM: The pathogenesis of non-alcoholic fatty liver disease (NAFLD)
      is multifactorial. There is sparse literature on the role of small intestinal
      bacterial overgrowth (SIBO) and toll-like receptor (TLR) signaling in NAFLD. The
      present study evaluated the relationship of SIBO with expression of TLR signaling
      genes in patients with NAFLD. METHODS: A total of 142 subjects composed of NAFLD
      (n = 60, mean age 38.7 +/- 10.4 years), chronic viral hepatitis (CVH) (n = 32,
      mean age 39.5 +/- 10.6 years), and healthy volunteers (n = 50, mean age 36.56 +/-
      4.2 years) were enrolled in the study. Duodenal fluid was taken endoscopically in
      32 prospective patients with NAFLD for evaluation of SIBO. Hepatic mRNA
      expression of TLR4, CD14, TLR2, NF-kappabeta, and MD2 and protein expression of
      TLR4 and TLR2 were studied in 64 patients (NAFLD = 32, CVH = 32) by RT-PCR and
      immunohistochemistry, respectively. Serum levels of TNF-alpha, adiponectin,
      insulin, and endotoxins were also evaluated. RESULTS: Small intestinal bacterial
      overgrowth was present in 12 (37.5%) out of 32 patients with NAFLD with
      Escherichia coli as the predominant bacterium. In comparison with those without
      SIBO, patients with SIBO had significantly higher endotoxin levels and higher
      CD14 mRNA, nuclear factor kappa beta mRNA, and TLR4 protein expression. Patients
      with NASH had significantly higher endotoxin levels and higher intensity of TLR4
      protein expression in comparison with patients without NASH. Serum levels of TNF
      alpha, endotoxins, and insulin were significantly higher and of adiponectin lower
      in NAFLD in comparison with CVH and healthy volunteers. CONCLUSIONS: Our study
      provides the first direct evidence of role of SIBO and endotoxemia and its
      relation with TLR signaling genes and liver histology in patients with NAFLD.

PMID- 26212090
TI  - Effect of Audiovisual Treatment Information on Relieving Anxiety in Patients
      Undergoing Impacted Mandibular Third Molar Removal.
AB  - PURPOSE: The authors hypothesized that an audiovisual slide presentation that
      provided treatment information regarding the removal of an impacted mandibular
      third molar could improve patient knowledge of postoperative complications and
      decrease anxiety in young adults before and after surgery. A group that received
      an audiovisual description was compared with a group that received the
      conventional written description of the procedure. MATERIALS AND METHODS: This
      randomized clinical trial included young adult patients who required surgical
      removal of an impacted mandibular third molar and fulfilled the predetermined
      criteria. The predictor variable was the presentation of an audiovisual
      slideshow. The audiovisual informed group provided informed consent after viewing
      an audiovisual slideshow. The control group provided informed consent after
      reading a written description of the procedure. The outcome variables were the
      State-Trait Anxiety Inventory, the Dental Anxiety Scale, a self-reported anxiety
      questionnaire, completed immediately before and 1 week after surgery, and a
      postoperative questionnaire about the level of understanding of potential
      postoperative complications. The data were analyzed with chi(2) tests,
      independent t tests, Mann-Whitney U  tests, and Spearman rank correlation
      coefficients. RESULTS: Fifty-one patients fulfilled the inclusion criteria. The
      audiovisual informed group was comprised of 20 men and 5 women; the written
      informed group was comprised of 21 men and 5 women. The audiovisual informed
      group remembered significantly more information than the control group about a
      potential allergic reaction to local anesthesia or medication and potential
      trismus (P < .05). The audiovisual informed group had lower self-reported anxiety
      scores than the control group 1 week after surgery (P < .05). CONCLUSION: These
      results suggested that informing patients of the treatment with an audiovisual
      slide presentation could improve patient knowledge about postoperative
      complications and aid in alleviating anxiety after the surgical removal of an
      impacted mandibular third molar.

PMID- 26212091
TI  - Natural Head Postures of Patients With Facial Asymmetry in Frontal View Are
      Corrected After Orthognathic Surgeries.
AB  - PURPOSE: Although orthognathic surgeries focus on adjustment of facial asymmetry
      (FA), many clinicians know by experience that the natural head posture (NHP) also
      is corrected after the surgery. The authors examined whether this was indeed the
      case by the measuring the NHP during the course of orthognathic treatment.
      Factors associated with NHP correction also were evaluated. PATIENTS AND METHODS:
      In this retrospective study, clinical features, including the NHP, of patients
      with FA and those with facial symmetry (FS) were compared. They were outpatients
      of a private orthodontic dental clinic from December 2008 to March 2012. The
      degree of NHP tilt was evaluated using an interpupillary (IP) horizontal angle.
      The NHP of patients with FA were analyzed further before presurgical orthodontic
      treatment, after presurgical orthodontic treatment, after orthognathic surgery
      and postsurgical orthodontic treatment, and 1 year after completion of
      postsurgical orthodontic treatment. The NHP difference at each time point was
      analyzed using 1-way analysis of variance. An analysis of factors that influence
      NHP tilt correction was performed by linear regression. RESULTS: Thirty-one
      patients with FA and 27 with FS were evaluated. The NHP tilt was more profound in
      the FA group compared with the FS group. There were more patients with skeletal
      Class III in the FA group. The degree of NHP tilt in the FA group was decreased
      after orthognathic surgery and postsurgical orthodontic treatment and remained
      when measured 1 year later. Women were less prone than men to NHP tilt correction
      by orthognathic surgery. CONCLUSION: Patients with FA have a tilted NHP compared
      with those with FS. Orthognathic surgery for FA might correct a tilted NHP to a
      lesser degree in women.

PMID- 26212092
TI  - Root Fragment Vitality After Coronectomy: Histological Evidence in a Case.
AB  - PURPOSE: Coronectomy is a well-documented surgical technique for the treatment of
      high-risk third molars, but the fate of retained roots remains controversial.
      This case report describes the histologic analysis of retained root fragments.
      PATIENT AND METHODS: A 44-year-old man treated with coronectomy of a left
      mandibular third molar requested the extraction of the retained roots. The
      patient was asymptomatic and the retained roots were extracted 18 months after
      coronectomy at the patient's request. RESULTS: The extracted roots were
      histologically evaluated and the results showed the presence of vital pulp
      tissue. CONCLUSION: Histologic analysis showed that retained roots remain vital
      after coronectomy.

PMID- 26212093
TI  - Is There Uniformity and Satisfaction Among Clinical Practice Models and Faculty
      Compensation Plans in US Dental School-Based Oral and Maxillofacial Surgery
      Departments?
AB  - PURPOSE: There is a lack of information regarding clinical practice models and
      faculty compensation plans used by dental school-based departments of oral and
      maxillofacial surgery (OMS) and their effectiveness. The purpose of this study
      was to examine 1) the level of uniformity in clinical practice models and faculty
      compensation plans for US dental school-based OMS departments and 2) the level of
      satisfaction expressed by faculty with their current compensation plan. MATERIALS
      AND METHODS: A survey was sent to the chairs of the 40 US dental school-based OMS
      departments asking them specific information regarding their current practice
      model, the faculty compensation plan, and their satisfaction with their current
      plan. RESULTS: Twenty-four of the 40 department chairs returned the survey, for a
      60% response rate. The OMS practice was part of the dental school faculty
      practice in 50% of the departments and a separate entity in 33%. The most common
      faculty compensation plan consisted of an academic salary plus a faculty practice
      salary based on a collection-based incentive (38%), but in 25% it was based on
      production. Fifty-seven percent of the responding chairs stated they were not
      satisfied with their current practice and compensation plans. CONCLUSIONS: There
      is considerable variation in the practice models and compensation plans in US
      dental school-based OMS departments. More than half the department chairs
      expressed a general dissatisfaction with their current compensation plans. The
      survey data indicate a need for alternative models, and this report presents one
      such model.

PMID- 26212094
TI  - Synovial Sarcoma of the Tongue: Report of a Case.
AB  - This report outlines the workup and management of a 55-year-old woman with a
      synovial sarcoma of the lateral border of the tongue that was initially diagnosed
      as a glomus tumor. A review was performed of the literature on synovial sarcomas
      of the oral cavity and current National Comprehensive Cancer Network guidelines.
      Synovial sarcomas of the tongue are rare neoplasms, with variable morphologic
      microscopic types and immunohistochemical profiles. Fluorescence in situ
      hybridization analysis of the known gene translocation also can be used in
      diagnosis. According to the literature, resection of the tumor is the current
      treatment of choice; however, owing to the rarity of this entity, diagnosis and
      management prove challenging for the oral and maxillofacial surgeon. 

PMID- 26212096
TI  - Nanostructural Characteristics and Interfacial Properties of Polymer Fibers in
      Cement Matrix.
AB  - Concrete is the most used material in the world. It is also one of the most
      versatile yet complex materials that humans have used for construction. However,
      an important weakness of concrete (cement-based composites) is its low tensile
      properties. Therefore, over the past 30 years many studies were focused on
      improving its tensile properties using a variety of physical and chemical
      methods. One of the most successful attempts is to use polymer fibers in the
      structure of concrete to obtain a composite with high tensile strength and
      ductility. The advantages of polymer fiber as reinforcing material in concrete,
      both with regard to reducing environmental pollution and the positive effects on
      a country's economy, are beyond dispute. However, a thorough understanding of the
      mechanical behavior of fiber-reinforced concrete requires a knowledge of
      fiber/matrix interfaces at the nanoscale. In this study, a combination of
      atomistic simulations and experimental techniques has been used to study the
      nanostructure of fiber/matrix interfaces. A new model for calcium-silicate
      hydrate (C-S-H)/fiber interfaces is also proposed on the basis of scanning
      electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX)
      analyses. Finally, the adhesion energy between the C-S-H gel and three different
      polymeric fibers (poly(vinyl alcohol), nylon-6, and polypropylene) were
      numerically studied at the atomistic level because adhesion plays a key role in
      the design of ductile fiber-reinforced composites. The mechanisms of adhesion as
      a function of the nanostructure of fiber/matrix interfaces are further studied
      and discussed. It is observed that the functional group in the structure of
      polymer macromolecule affects the adhesion energy primarily by changing the C/S
      ratio of the C-S-H at the interface and by absorbing additional positive ions in
      the C-S-H structure. 

PMID- 26212095
TI  - Tools to Assess Pain or Lack of Comfort in Dementia: A Content Analysis.
AB  - CONTEXT: There is need for tools to help detect pain or lack of comfort in
      persons unable to communicate. However, pain and (dis)comfort tools have not been
      compared, and it is unclear to what extent they discriminate between pain and
      other possible sources of discomfort, or even if items differ. OBJECTIVES: To map
      and compare items in tools that assess pain and the broader notion of discomfort
      or comfort in people with severe dementia or at the end of life. METHODS: Using
      qualitative content analysis with six classifications, we categorized each item
      of four thoroughly tested observational pain tools (Pain Assessment in Advanced
      Dementia [PAINAD], Pain Assessment Checklist for Seniors with Limited Ability to
      Communicate [PACSLAC], Doloplus-2, and draft Pain Assessment in Impaired
      Cognition [PAIC]), and four discomfort tools (including distress, comfort, and
      quality of life in severe dementia or at the end of life; Discomfort Scale
      Dementia Alzheimer Type [DS-DAT], Disability Distress Assessment Tool [DisDAT],
      End-of-Life in Dementia-Comfort Assessment in Dying with Dementia [EOLD-CAD], and
      Quality of Life in Late-Stage Dementia [QUALID] scale). We calculated median
      proportions to compare distributions of categories of pain and discomfort tools.
      RESULTS: We found that, despite variable content across tools, items from pain
      and discomfort tools overlapped considerably. For example, positive elements such
      as smiling and spiritual items were more often included in discomfort tools but
      were not unique to these. Pain tools comprised more "mostly descriptive" (median
      0.63 vs. 0.44) and fewer "highly subjective" items (0.06 vs. 0.18); some used
      time inconsistently, mixing present and past observations. CONCLUSION: This
      analysis may inform a more rigorous theoretical underpinning and (re)development
      of pain and discomfort tools and calls for empirical testing of a broad item pool
      for sensitivity and specificity in detecting and discriminating pain from other
      sources of discomfort.

PMID- 26212097
TI  - Allosterism in human complement component 5a ((h)C5a): a damper of C5a receptor
      (C5aR) signaling.
AB  - The phenomena of allosterism continues to advance the field of drug discovery, by
      illuminating gainful insights for many key processes, related to the structure
      function relationships in proteins and enzymes, including the transmembrane G
      protein coupled receptors (GPCRs), both in normal as well as in the disease
      states. However, allosterism is completely unexplored in the native protein
      ligands, especially when a small covalent change significantly modulates the
      pharmacology of the protein ligands toward the signaling axes of the GPCRs. One
      such example is the human C5a ((h)C5a), the potent cationic anaphylatoxin that
      engages C5aR and C5L2 to elicit numerous immunological and non-immunological
      responses in humans. From the recently available structure-function data, it is
      clear that unlike the mouse C5a ((m)C5a), the (h)C5a displays conformational
      heterogeneity. However, the molecular basis of such conformational heterogeneity,
      otherwise allosterism in (h)C5a and its precise contribution toward the overall
      C5aR signaling is not known. This study attempts to decipher the functional role
      of allosterism in (h)C5a, by exploring the inherent conformational dynamics in
      (m)C5a, (h)C5a and in its point mutants, including the proteolytic mutant des
      Arg(74)-(h)C5a. Prima facie, the comparative molecular dynamics study, over total
      500 ns, identifies Arg(74)-Tyr(23) and Arg(37)-Phe(51) "cation-pi" pairs as the
      molecular "allosteric switches" on (h)C5a that potentially functions as a damper
      of C5aR signaling. 

PMID- 26212098
TI  - Primary combined neuroendocrine carcinoma (small-cell type) and squamous cell
      carcinoma of the colon.

PMID- 26212099
TI  - Antioxidant, cholinesterase inhibition activities and essential oil analysis of
      Nelumbo nucifera seeds.
AB  - Nelumbo nucifera seeds' essential oil (EO), crude extract and subsequent
      fractions were evaluated for their DPPH, ABTS and superoxide anion-free radical
      scavenging and cholinesterase inhibitory activities. The ethyl acetate fraction
      and EO showed outstanding antioxidant activities with IC50 values of 191, 450
      MUg/mL (DPPH), 123, 221 MUg/mL (ABTS) and 69, 370 MUg/mL (superoxide anion). The
      ethyl acetate fraction and EO also caused significant inhibition of
      acetylcholinesterase and butyrylcholinesterase with IC50 values of 70 +/- 0.6, 64
      +/- 0.8 and 75 +/- 0.3, 58 +/- 0.2, in dose-dependent manner. The first ever gas
      chromatography-mass spectrometry analysis of the EO obtained from N. nucifera
      seeds resulted in identification of 19 constituents, mainly comprised of
      oxygenated sesquiterpenes responsible for their promising bioactivity. The crude
      and fractions revealed the presence of saponins, flavonoids, steroids, alkaloids,
      terpenoids and cardiac glycosides in phytochemical investigation. 

PMID- 26212100
TI  - Evaluation of a one-piece ceramic implant used for single-tooth replacement and
      three-unit fixed partial dentures: a prospective cohort clinical trial.
AB  - AIM: The aim of this clinical trial was to evaluate the safety and efficiency of
      a one-piece zirconia oral implant after 1 year of function. MATERIALS AND
      METHODS: Two centers included 60 subjects in need of implant-supported single
      tooth restorations or three-unit bridges. A total of 71 zirconia one-piece
      implants were placed and immediately restored with a temporary reconstruction for
      at least 2 months. The final veneered zirconia restorations were then cemented
      and followed for 6 months and 1 year after insertion of the restorations. At each
      visit, a clinical evaluation was performed to analyze biological parameters of
      the implants and the neighboring teeth. A standardized periapical radiograph was
      taken at implant insertion, at the placement of the restorations and at the 1
      year follow-up. RESULTS: Sixty patients with 71 implants (48 in the mandible, 23
      in the maxilla) were included in this study and provided with 11 bridges and 49
      crowns. Two patients with three implants (one bridge and one single crown) could
      not be evaluated. One patient lost his implant 5 weeks after implant insertion.
      Based on 58 patients, the mean survival rate was 98.3% after one year when the
      implants of the two patients that did not show up were not counted as lost. The
      mean marginal bone loss from implant insertion to the 1-year follow-up after the
      final prosthetic restoration was 0.78 mm with a standard deviation of 0.79 mm.
      The probing depth around the implants increased from 2.7 mm at insertion of the
      prosthetic reconstruction to 3.5 mm one year after insertion. The probing depth
      around the adjacent teeth remained stable at 2.5 mm. At the 1-year recall, the
      difference was significant. The clinical attachment levels at implants and teeth
      were not different at the 1-year follow-up with 3.1 mm at tooth and implant
      sites. CONCLUSIONS: The presently tested one-piece ceramic implant was successful
      in replacing single tooth and three-unit gaps after one year of function. Further
      long-term data are necessary to verify these initial findings.

PMID- 26212101
TI  - Development of a rapid HRM genotyping method for detection of dog-derived Giardia
      lamblia.
AB  - Giardia lamblia is a zoonotic flagellate protozoan in the intestine of human and
      many mammals including dogs. To assess a threat of dog-derived G. lamblia to
      humans, the common dog-derived G. lamblia assemblages A, C, and D were genotyped
      by high-resolution melting (HRM) technology. According to beta-giardin gene
      sequence, the qPCR-HRM primers BG5 and BG7 were designed. A series of experiments
      on the stability, sensitivity, and accuracy of the HRM method were also tested.
      Results showed that the primers BG5 and BG7 could distinguish among three
      assemblages A, C, and D, which Tm value differences were about 1  degrees C to
      each other. The melting curves of intra-assay reproducibility were almost
      coincided, and those of inter-assay reproducibility were much the same shape. The
      lowest detection concentration was about 5 * 10(-6)-ng/MUL sample. The genotyping
      results from 21 G. lamblia samples by the HRM method were in complete accordance
      with sequencing results. It is concluded that the HRM genotyping method is rapid,
      stable, specific, highly sensitive, and suitable for clinical detection and
      molecular epidemiological survey of dog-derived G. lamblia. 

PMID- 26212103
TI  - Nurses' perceptions of workplace culture in primary health care in Finland.
AB  - AIM: This study aimed to describe nurses' perceptions of workplace culture,
      especially in regard to stress levels, job satisfaction and the practice
      environment in primary health care. BACKGROUND: Health care is facing many
      challenges related to its attractiveness as a place of employment and the
      maintenance of a sufficient workforce supply. Previous studies report increasing
      rates of nurse job dissatisfaction and intentions to leave their current
      positions both in Finland and also globally. Improving workplace culture is thus
      vital in meeting the challenges related to recruitment and retention. METHODS: A
      cross-sectional descriptive design was used to describe nurses' perceptions of
      workplace culture. Data were collected by questionnaire from 22 units in nine
      primary healthcare organizations in Finland, and analysed using descriptive and
      inferential statistics. RESULTS: Most of the respondents indicated that they were
      not certain whether their workplace culture was either positive or negative.
      Profession, age and work shift characteristics had an effect on the respondents'
      perceptions of workplace culture. Younger licensed practical and registered
      nurses assessed their workplace culture more positively, whereas older registered
      nurses and those working rotating rosters viewed workplace culture more
      negatively. CONCLUSIONS: The findings suggest that both unit and demographic
      characteristics affect workplace culture. This survey highlights that a positive
      workplace culture is one of the key factors in retaining and recruiting nurses,
      and provides an essential evidence that may be considered by other healthcare
      organizations. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse managers and
      healthcare leaders need to address workload management and take into account the
      related variables that affect a unit's workplace culture.

PMID- 26212102
TI  - Cryptosporidium species and subtype analysis in diarrhoeic pre-weaned lambs and
      goat kids from north-western Spain.
AB  - Faecal specimens from diarrhoeic pre-weaned lambs (n = 171) and goat kids (n =
      118) were collected in 37 sheep and 23 goat flocks, respectively, from NW Spain
      and microscopically examined for the presence of Cryptosporidium oocysts.
      Positive specimens were selected for molecular characterization. Presence of
      Cryptosporidium oocysts were significantly higher in specimens from goat kids
      (62.7%) than from lambs (31.6%). PCR products of the SSU rRNA locus were obtained
      for 108 isolates, and three Cryptosporidium species were identified.
      Cryptosporidium parvum was the most common species identified from both lambs
      (74.4%) and goat kids (93.8%). The remaining PCR products from lambs (25.6%) and
      goat kids (7.7%) were identified as Cryptosporidium Ubiquitum and Cryptosporidium
      xiaoi, respectively. Five C. parvum subtypes were identified; IIaA13G1R1,
      IIaA14G2R1, IIaA15G2R1 and IIaA16G3R1 were found in both host species, and
      IIdA17G1 was only detected in goat kids. Subtype IIaA15G2R1 was the most common
      and widely distributed. The present study provides the first description of
      subtypes IIaA13G1R1 in both small ruminant species, IIaA14G2R1 in sheep and
      IIaA16G3R1 in goats. Our results also reveal that diarrhoeic pre-weaned lambs and
      goat kids must be considered important reservoirs of Cryptosporidium species with
      zoonotic potential, such as C. parvum and C. ubiquitum.

PMID- 26212104
TI  - Systematic review of studies investigating the association between dietary habits
      and cutaneous malignant melanoma.
AB  - OBJECTIVE: Several papers have dealt with diet as a risk factor for cutaneous
      malignant melanoma (CMM). This study aimed to synthesize available data on the
      topic. STUDY DESIGN: A systematic review of observational studies assessing the
      association between dietary habits and CMM was performed. METHODS: Electronic
      databases were used to identify eligible articles. Quality was assessed through
      the Newcastle-Ottawa scale. Case-control and cohort studies evaluating the intake
      of food/nutrients through the assessment of dietary habits and the occurrence of
      CMM were considered eligible. Data comparing the highest and lowest levels of
      consumption were collected from single studies and described qualitatively as
      data combination was not possible. Results were reported as percentages on the
      basis of relative risks and odds ratios. RESULTS: Eighteen studies reported in 21
      articles were selected. Cohort studies showed better quality than case-control
      studies. Most articles did not detect any significant association between
      food/nutrient intake and CMM, except for limited evidence of a protective role
      associated with fish, vegetables and fruit. Risk reduction was shown to be 35
      37%, 40-57% and 34-46%, respectively, in studies reporting significant results.
      Similarly, few articles showed protective roles of beta-carotene and vitamins A,
      C, D and E, with risk reduction of 64%, 37-43%, 41%, 15-39% and 50-66%,
      respectively. CONCLUSION: A trend towards reduced risk of CMM associated with
      higher intake of fish, vegetables and fruit, as well as beta-carotene and
      vitamins A, C, D and E, has been shown but further research is needed to provide
      decisive data.

PMID- 26212105
TI  - Targeting the CD80/CD86 costimulatory pathway with CTLA4-Ig directs microglia
      toward a repair phenotype and promotes axonal outgrowth.
AB  - Among the costimulatory factors widely studied in the immune system is the
      CD28/cytotoxic T-lymphocyte antigen-4 (CTLA4)-CD80/CD86 pathway, which critically
      controls the nature and duration of the T-cell response. In the brain, up
      regulated expression of CD80/CD86 during inflammation has consistently been
      reported in microglia. However, the role of CD80/CD86 molecules has mainly been
      studied in a context of microglia-T cell interactions in pathological conditions,
      while the function of CD80/CD86 in the regulation of intrinsic brain cells
      remains largely unknown. In this study, we used a transgenic pig line in which
      neurons express releasable CTLA4-Ig, a synthetic molecule mimicking CTLA4 and
      binding to CD80/CD86. The effects of CTLA4-Ig on brain cells were analyzed after
      intracerebral transplantation of CTLA4-Ig-expressing neurons or wild-type neurons
      as control. This model provided in vivo evidence that CTLA4-Ig stimulated axonal
      outgrowth, in correlation with a shift of the nearby microglia from a compact to
      a ramified morphology. In a culture system, we found that the CTLA4-Ig-induced
      morphological change of microglia was mediated through CD86, but not CD80. This
      was accompanied by microglial up-regulated expression of the anti-inflammatory
      molecule Arginase 1 and the neurotrophic factor BDNF, in an astrocyte-dependent
      manner through the purinergic P2Y1 receptor pathway. Our study identifies for the
      first time CD86 as a key player in the modulation of microglia phenotype and
      suggests that CTLA4-Ig-derived compounds might represent new tools to manipulate
      CNS microglia.

PMID- 26212106
TI  - May the surface roughness of the retrieved femoral head influence the wear
      behavior of the polyethylene liner?
AB  - This study was aimed at determining the surface degradation occurred on retrieved
      ceramic and metallic heads, as well as the influence of the head surface quality
      on the wear of the polyethylene counterface. To this purpose, 14 ceramic and 14
      metallic femoral heads retrieved at revision surgery were examined. Scanning
      electron microscopic analysis provided visual evidence that some metallic heads
      presented crescent wear more often than the ceramic ones; the former showed a
      higher volumetric loss (as determined by Coordinate Measuring Machine) than the
      latter, but less negative Rsk values. This apparent lack of correlation between
      volumetric loss (i.e., wear factor) and roughness data may be explained by
      considering that they are two temporally variant parameters. No significant
      differences were observed between the Ra values of the two sets of femoral heads.
      The cups articulating against metal heads were characterized by higher mean wear
      volumes than those articulating against alumina although this difference was not
      statistically significant; metal heads displayed significantly higher mean wear
      volumes than alumina heads. The micro-Raman analysis of the cup articulated
      against the most worn alumina femoral head showed an orthorhombic into monoclinic
      phase transformation that was not observed in the cups coupled to metal heads.
      The obtained results showed that the surface finishing of the femoral head (in
      terms of Rsk values) determined the morphological changes experienced by the
      ultra-high-molecular-weight polyethylene crystalline phase at the molecular
      level. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater,
      104B: 1374-1385, 2016.

PMID- 26212107
TI  - Directionality of substrate translocation of the hemolysin A Type I secretion
      system.
AB  - Type 1 secretion systems (T1SS) of Gram-negative bacteria are responsible for the
      secretion of various proteases, lipases, S-layer proteins or toxins into the
      extracellular space. The paradigm of these systems is the hemolysin A (HlyA) T1SS
      of Escherichia coli. This multiple membrane protein complex is able to secrete
      the toxin HlyA in one step across both E. coli membranes. Common to all secreted
      T1SS substrates is a C-terminal secretion sequence being necessary as well as
      sufficient for secretion. However, it is not known whether transport occurs
      directionally, i.e. the N- or the C-terminus of T1SS substrates is secreted
      first. We have addressed this question by constructing HlyA fusions with the
      rapidly folding eGFP resulting in a stalled T1SS. Differential labeling and
      subsequent fluorescence microscopic detection of C- and N-terminal parts of the
      fusions allowed us to demonstrate vectorial transport of HlyA through the T1SS
      with the C-terminus appearing first outside the bacterial cells. 

PMID- 26212108
TI  - Homoserine Lactones, Methyl Oligohydroxybutyrates, and Other Extracellular
      Metabolites of Macroalgae-Associated Bacteria of the Roseobacter Clade:
      Identification and Functions.
AB  - Twenty-four strains of marine Roseobacter clade bacteria were isolated from
      macroalgae and investigated for the production of quorum-sensing autoinducers, N
      acylhomoserine lactones (AHLs). GC/MS analysis of the extracellular metabolites
      allowed us to evaluate the release of other small molecules as well. Nineteen
      strains produced AHLs, ranging from 3-OH-C10:0-HSL (homoserine lactone) to
      (2E,11Z)-C18:2-HSL, but no specific phylogenetic or ecological pattern of
      individual AHL occurrence was observed when cluster analysis was performed. Other
      identified compounds included indole, tropone, methyl esters of oligomers of 3
      hydroxybutyric acid, and various amides, such as N-9-hexadecenoylalanine methyl
      ester (9-C16:1-NAME), a structural analogue of AHLs. Several compounds were
      tested for their antibacterial and antialgal activity on marine isolates likely
      to occur in the habitat of the macroalgae. Both AHLs and 9-C16:1-NAME showed high
      antialgal activity against Skeletonema costatum, whereas their antibacterial
      activity was low. 

PMID- 26212109
TI  - Chemical Synthesis Elucidates the Immunological Importance of a Pyruvate
      Modification in the Capsular Polysaccharide of Streptococcus pneumoniae Serotype
      4.
AB  - Carbohydrate modifications are believed to strongly affect the immunogenicity of
      glycans. Capsular polysaccharides (CPS) from bacterial pathogens are frequently
      equipped with a pyruvate that can be placed across the 4,6-, 3,4-, or 2,3
      positions. A trans-2,3-linked pyruvate is present on the CPS of the Gram-positive
      bacterium Streptococcus pneumoniae serotype 4 (ST4), a pathogen responsible for
      pneumococcal infections. To assess the immunological importance of this
      modification within the CPS repeating unit, the first total synthesis of the
      glycan was carried out. Glycan microarrays containing a series of synthetic
      antigens demonstrated how antibodies raised against natural ST4 CPS specifically
      recognize the pyruvate within the context of the tetrasaccharide repeating unit.
      The pyruvate modification is a key motif for designing minimal synthetic
      carbohydrate vaccines for ST4. 

PMID- 26212110
TI  - Corrigendum.

PMID- 26212112
TI  - A qualitative study on the challenges associated with accepting familial support
      from the perspective of transition-age youth with eating disorders.
AB  - The aim of this study was to identify types of family support desired by young
      adults with eating disorders during the transfer of care from paediatric to adult
      eating disorders programs. Using constant comparative analysis, two salient
      themes from qualitative interviews with 15 young adults were identified: (a)
      uncertainty about the role of parents in maintaining recovery during the
      transfer; and (b) the need for parental support, defined as assistance with
      eating and maintenance of recovery. Young adults voiced that parental emotional
      involvement and assistance with navigating adult care services is critical to
      their successful transfer between the two systems of care. 

PMID- 26212111
TI  - Impact of Antiinflammatory Treatment on the Onset of Uveitis in Juvenile
      Idiopathic Arthritis: Longitudinal Analysis From a Nationwide Pediatric
      Rheumatology Database.
AB  - OBJECTIVE: Based on a nationwide database, this study analyzed the influence of
      methotrexate (MTX), tumor necrosis factor (TNF) inhibitors, and a combination of
      the 2 medications on uveitis occurrence in juvenile idiopathic arthritis (JIA)
      patients. METHODS: Data from the National Paediatric Rheumatological Database in
      Germany were used in this study. Between 2002 and 2013, data from JIA patients
      were annually documented at the participating pediatric rheumatologic sites.
      Patients with a JIA disease duration of <12 months at initial documentation and
      >=2 years of followup were included in this study. The impact of antiinflammatory
      treatment on the occurrence of uveitis was evaluated by discrete-time survival
      analysis. RESULTS: A total of 3,512 JIA patients (mean +/- SD age 8.3 +/- 4.8
      years, 65.7% female, 53.2% antinuclear antibody positive, and mean +/- SD age at
      arthritis onset 7.8 +/- 4.8 years) fulfilled the inclusion criteria. Mean +/- SD
      total followup time was 3.6 +/- 2.4 years. Uveitis developed in a total of 180
      patients (5.1%) within 1 year after arthritis onset. Uveitis onset after the
      first year was observed in another 251 patients (7.1%). Disease-modifying
      antirheumatic drug (DMARD) treatment in the year before uveitis onset
      significantly reduced the risk for uveitis as follows: MTX: hazard ratio (HR)
      0.63, P = 0.022; TNF inhibitors: HR 0.56, P < 0.001; and a combination of the 2
      medications: HR 0.10, P < 0.001. Patients treated with MTX within the first year
      of JIA had an even a lower uveitis risk (HR 0.29, P < 0.001). CONCLUSION: The use
      of DMARDs in JIA patients significantly reduced the risk for uveitis onset. Early
      MTX use within the first year of disease and the combination of MTX with a TNF
      inhibitor had the highest protective effect.

PMID- 26212113
TI  - Influence of the proton pump inhibitor lansoprazole on distribution and activity
      of doxorubicin in solid tumors.
AB  - Cellular causes of resistance and limited drug distribution within solid tumors
      limit therapeutic efficacy of anticancer drugs. Acidic endosomes in cancer cells
      mediate autophagy, which facilitates survival of stressed cells, and may
      contribute to drug resistance. Basic drugs (e.g. doxorubicin) are sequestered in
      acidic endosomes, thereby diverting drugs from their target DNA and decreasing
      penetration to distal cells. Proton pump inhibitors (PPIs) may raise endosomal
      pH, with potential to improve drug efficacy and distribution in solid tumors. We
      determined the effects of the PPI lansoprazole to modify the activity of
      doxorubicin. To gain insight into its mechanisms, we studied the effects of
      lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and
      of biomarkers reflecting its activity, using in vitro and murine models.
      Lansoprazole showed concentration-dependent effects to raise endosomal pH and to
      inhibit endosomal sequestration of doxorubicin in cultured tumor cells.
      Lansoprazole was not toxic to cancer cells but potentiated the cytotoxicity of
      doxorubicin and enhanced its penetration through multilayered cell cultures. In
      solid tumors, lansoprazole improved the distribution of doxorubicin but also
      increased expression of biomarkers of drug activity throughout the tumor.
      Combined treatment with lansoprazole and doxorubicin was more effective in
      delaying tumor growth as compared to either agent alone. Together, lansoprazole
      enhances the therapeutic effects of doxorubicin both by improving its
      distribution and increasing its activity in solid tumors. Use of PPIs to improve
      drug distribution and to inhibit autophagy represents a promising strategy to
      enhance the effectiveness of anticancer drugs in solid tumors.

PMID- 26212115
TI  - Efficacy and safety of therapeutic plasma exchange by using apheresis devices in
      pediatric atypical hemolytic uremic syndrome patients.
AB  - BACKGROUND: Therapeutic plasma exchange (TPE) in atypical hemolytic uremic
      syndrome (aHUS) is considered as first line treatment as per current American
      Society for Apheresis (ASFA) guidelines. But there is very limited data available
      in the literature regarding efficacy and safety of TPE procedures in pediatric
      aHUS patients. AIM: To assess the safety and efficacy of TPE by using apheresis
      devices in pediatric aHUS patients. MATERIALS AND METHODS: We did a retrospective
      analysis of all TPE procedures performed in aHUS pediatric patients over a period
      of 13 years (2001-2013). TPE procedures were done on two different devices daily
      or on alternate days depending on clinical condition of the patient. Adverse
      events if any were noted and analyzed. Pre and post procedural laboratory
      profiles were analyzed to assess the response to TPE therapy and patients were
      categorized accordingly. RESULTS: A total of 169 TPE procedures (range of 1
      22/patient with an average of 7.6 procedures/patient) were performed on 30
      pediatric patients. Twenty four patients had more than 3 TPE procedures. Sixteen
      patients were complete responders, 5 were partial responders and 3 were non
      responders. The time between onset of illness and start of TPE therapy was 1-4
      days in complete responders, 5-7 days in partial responders and 8-9 days in non-
      responders. Adverse events were observed in 13 (7.7%) procedures. CONCLUSION: TPE
      is a safe and effective therapeutic modality in pediatric aHUS if instituted
      early in the course of disease with a minimum of four to five procedures. J.
      Clin. Apheresis 31:381-387, 2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26212114
TI  - Breath testing as potential colorectal cancer screening tool.
AB  - Although colorectal cancer (CRC) screening is included in organized programs of
      many countries worldwide, there is still a place for better screening tools. In
      this study, 418 breath samples were collected from 65 patients with CRC, 22 with
      advanced or nonadvanced adenomas, and 122 control cases. All patients, including
      the controls, had undergone colonoscopy. The samples were analysed with two
      different techniques. The first technique relied on gas chromatography coupled
      with mass spectrometry (GC-MS) for identification and quantification of volatile
      organic compounds (VOCs). The T-test was used to identify significant VOCs (p
      values < 0.017). The second technique relied on sensor analysis with a pattern
      recognition method for building a breath pattern to identify different groups.
      Blind analysis or leave-one-out cross validation was conducted for validation.
      The GC-MS analysis revealed four significant VOCs that identified the tested
      groups; these were acetone and ethyl acetate (higher in CRC), ethanol and 4
      methyl octane (lower in CRC). The sensor-analysis distinguished CRC from the
      control group with 85% sensitivity, 94% specificity and 91% accuracy. The
      performance of the sensors in identifying the advanced adenoma group from the non
      advanced adenomas was 88% sensitivity, 100% specificity, and 94% accuracy. The
      performance of the sensors in identifying the advanced adenoma group was
      distinguished from the control group was 100% sensitivity, 88% specificity, and
      94% accuracy. For summary, volatile marker testing by using sensor analysis is a
      promising noninvasive approach for CRC screening. 

PMID- 26212116
TI  - Periconceptional Folic Acid Supplementation and Infant Risk of Congenital Heart
      Defects in Norway 1999-2009.
AB  - BACKGROUND: The birth prevalence of congenital heart defects (CHDs) has decreased
      in Canada and Europe. Recommended intake of folic acid in pregnancy is a
      suggestive risk-reducing factor for CHDs. We investigated the association between
      periconceptional intake of folic acid supplements and infant risk of CHDs.
      METHODS: Information on maternal intake of folic acid supplements before and
      during pregnancy in the Medical Birth Registry of Norway 1999-2009 was updated
      with information on CHD diagnoses from national health registers and the
      Cardiovascular Diseases in Norway Project. The association between folic acid
      intake and infant risk of CHD was estimated as relative risk (RR) with binomial
      log linear regression. RESULTS: Among 517 784 non-chromosomal singleton births,
      6200 children were identified with CHD and 1153 with severe CHD. For all births,
      18.4% of the mothers initiated folic acid supplements before pregnancy and 31.6%
      during pregnancy. The adjusted RR for severe CHD was 0.99 [95% confidence
      interval [CI] 0.86, 1.13] comparing periconceptional intake of folic acid with no
      intake. Specifically, RR for conotruncal defects was 0.99 [95% CI 0.80, 1.22],
      atrioventricular septal defects 1.19 [95% CI 0.78, 1.81], left ventricular
      outflow tract obstructions 1.02 [95% CI 0.78, 1.32], and right ventricular
      outflow tract obstructions 0.97 [95% CI 0.72, 1.29]. Birth prevalence of septal
      defects was higher in the group exposed to folic acid supplements with RR 1.19
      [95% CI 1.10, 1.30]. CONCLUSIONS: Periconceptional folic acid supplement use
      showed no association with severe CHDs in the newborn. An unexpected association
      with an increased risk of septal defects warrants further investigation.

PMID- 26212117
TI  - Isolated musculocutaneous nerve injury in a kickboxer.

PMID- 26212118
TI  - The role of the bile acid chenodeoxycholic acid in the targeted oral delivery of
      the anti-diabetic drug gliclazide, and its applications in type 1 diabetes.
AB  - Gliclazide (G) is used to treat type 2 diabetes (T2D), and also has anti
      platelet, anti-radical, and anti-inflammatory effects. G has poor water
      solubility and high inter-individual variations in absorption, limiting its
      application in type 1 diabetes (T1D). The bile acid, chenodeoxycholic acid
      (CDCA), has permeation-enhancing effects. Sodium alginate (SA) was used to
      microencapsulate G and CDCA to produce control (G-SA) and test (G-CDCA-SA)
      microcapsules. Both microcapsules showed uniform structure, morphology, and good
      stability profiles. CDCA reduced G-release at pH 7.8, while G-release was
      negligible at lower pH values in both microcapsules. CDCA incorporation resulted
      in less swelling and stronger microcapsules, suggesting improved stability. 

PMID- 26212119
TI  - Cardiovascular risk factors, burden of disease and preventive strategies in
      patients with systemic lupus erythematosus: a literature review.
AB  - INTRODUCTION: Risk of developing cardiovascular disease (CVD) is increased in
      systemic lupus erythematosus (SLE) compared with the general population.
      Traditional risk factors cannot account for the totality of CV events and
      adequate prevention may be challenging. AREAS COVERED: This review summarizes
      traditional and emerging risk factors of CVD in SLE patients and goes over
      potential pathogenic mechanisms involved in CVD development. Role of commonly
      used drugs and preventive strategies exploitable in everyday clinical practice
      are also discussed. EXPERT OPINION: SLE-related risk factors involve both disease
      and treatment-related features, including disease activity, disease phenotype,
      corticosteroid misuse and alterations of innate and adaptive immunity. Primary
      prevention is mandatory in management of lupus patients through appropriate
      disease control, corticosteroid tapering, use of antimalarials and eventually
      vitamin D supplementation.

PMID- 26212120
TI  - Characterization of LipN (Rv2970c) of Mycobacterium Tuberculosis H37Rv and its
      Probable Role in Xenobiotic Degradation.
AB  - LipN (Rv2970c) belongs to the Lip family of M. tuberculosis H37Rv and is
      homologous to the human Hormone Sensitive Lipase. The enzyme demonstrated
      preference for short carbon chain substrates with optimal activity at 45 degrees
      C/pH 8.0 and stability between pH 6.0-9.0. The specific activity of the enzyme
      was 217 U/mg protein with pNP-butyrate as substrate. It hydrolyzed tributyrin to
      di- and monobutyrin. The active-site residues of the enzyme were confirmed to be
      Ser216, Asp316, and His346. Tetrahydrolipstatin, RHC-80267 and N-bromosuccinimide
      inhibited LipN enzyme activity completely. Interestingly, Trp145, a non active
      site residue, demonstrated functional role to retain enzyme activity. The enzyme
      was localized in cytosolic fraction of M. tuberculosis H37Rv. The enzyme was able
      to synthesize ester of butyric acid, methyl butyrate, in presence of methanol.
      LipN was able to hydrolyze 4-hydroxyphenylacetate to hydroquinone. The gene was
      not expressed in in-vitro growth conditions while the expression of rv2970c gene
      was observed post 6h of macrophage infection by M. tuberculosis H37Ra. Under
      individual in-vitro stress conditions, the gene was expressed during acidic
      stress condition only. These findings suggested that LipN is a cytosolic, acid
      inducible carboxylesterase with no positional specificity in demonstrating
      activity with short carbon chain substrates. It requires Trp145, a non active
      site residue, for it's enzyme activity.

PMID- 26212121
TI  - Biochemical capacitance of Geobacter sulfurreducens biofilms.
AB  - An electrical model able to decouple the electron pathway from microbial cell
      machinery impedance terms is introduced. In this context, capacitance
      characteristics of the biofilm are clearly resolved. In other words, the model
      allows separating, according to the advantage of frequency and spectroscopic
      response approach, the different terms controlling the performance of the
      microbial biofilm respiratory process and thus the directly related electricity
      production process. The model can be accurately fitted to voltammetry
      measurements obtained under steady-state conditions and also to biofilm discharge
      amperometric measurements. The implications of biological aspects of the
      electrochemical or redox capacitance are discussed theoretically in the context
      of current knowledge with regard to structure and physiological activity of
      microbial Geobacter biofilms. 

PMID- 26212122
TI  - Hydrothermal Synthesis of Unique Hollow Hexagonal Prismatic Pencils of Co3 V2 O8
      ?n H2 O: A New Anode Material for Lithium-Ion Batteries.
AB  - Hollow structures of transition-metal oxides, particularly mixed-metal oxides,
      could be promising for various applications such as lithium-ion batteries (LIBs).
      Compared to the synthesis of metal oxide hollow spheres by the template method,
      non-spherical metal oxide hollow hexagonal polyhedra have not been developed to
      date. Herein, we report the controlled hydrothermal synthesis of a new phase of
      Co3 V2 O8 ?n H2 O hollow hexagonal prismatic pencils (HHPPs), which is composed
      of uniform structural units. By varying the amount of NaOH in the presence of NH4
      (+) and without any template or organic surfactant, the hexagonal prismatic
      pencils gradually transform from solid into hollow structures, with sizes varying
      from 5 to 20 MUm. The structure of pencils can be preserved only in a limited
      range of the molar ratio of OH(-) /NH4 (+) . As a new anode material for LIBs,
      such hollow pencils exhibit impressive lithium storage properties with high
      capacity, good cycling stability, and superior rate capability.

PMID- 26212123
TI  - Primary cutaneous nocardiosis caused by Nocardia concava.

PMID- 26212124
TI  - Intestinal Immunity and Gut Microbiota as Therapeutic Targets for Preventing
      Atherosclerotic Cardiovascular Diseases.
AB  - Atherosclerosis is considered a chronic inflammatory disease and an intervention
      targeting the inflammatory process could be a new therapeutic strategy for
      preventing atherosclerotic cardiovascular diseases (CVD). We hypothesized that
      the intestine, which is considered the biggest immune organ in the human body,
      could be a therapeutic target for preventing CVD. We demonstrated that oral
      administration of anti-CD3 antibody or an active form of vitamin D3 reduced
      atherosclerosis in mice via induction of regulatory T cells and tolerogenic
      dendritic cells in the gut-associated lymphoid tissues. Similar to regulatory
      immune responses achieved by oral tolerance, our method had systemic effects that
      ultimately contributed towards atherosclerosis reduction. Recently, we have been
      interested in the gut microbiota, which have been reported as highly associated
      with intestinal immunity and systemic metabolic disorders, including obesity and
      diabetes. Notably, the guts of obese individuals are predominantly colonized by
      Firmicutes over Bacteroidetes. The association between atherosclerosis and
      microbiota has been attracting increased attention, and gut microbiota have been
      shown to participate in the metabolism of a proatherogenic compound called
      trimethylamine-N-oxide (TMAO) and aggravate CVD. Our investigation of the
      relationship between susceptibility to CVD and the gut microbiota revealed a
      characteristic flora type. Here, we discuss the evidence for the relationship
      between the gut microbiota and cardiometabolic diseases, and consider the gut
      microbiota as new potential therapeutic targets for treating CVD. (Circ J 2015;
      79: 1882-1890).

PMID- 26212125
TI  - Use patterns of health information exchange systems and admission decisions:
      Reductionistic and configurational approaches.
AB  - BACKGROUND: Research that endeavors to identify the value of electronic health
      information exchange (HIE) systems to the healthcare industry and, specifically,
      to clinical decision making is often inconclusive or theory-based. Studies
      seeking to identify how clinical decisions relate to patterns of actual HIE use,
      often by analyzing system log files, generally rely on dichotomous distinctions
      between system use and no-use, disregard the availability of information in the
      system, and control for few user characteristics. OBJECTIVE: We aim at
      empirically exploring the associations between use patterns of HIE systems and
      subsequent clinical decisions on the basis of broad definitions of use patterns,
      available information, and control variables. METHODS: We examine the decision to
      admit critically-ill patients either to the intensive care unit (ICU) or to
      another ward at a busy emergency department in the period 2010-2012. Using HIE
      log files, use patterns are characterized by the variables of number of users,
      volume, diversity, granularity, duration, and content. We test the association
      between HIE use patterns and the admission decision, after controlling for
      multiple demographic, clinical, physician, and situational variables and for
      available HIE information. This association is examined by taking a
      reductionistic approach that focuses on independent use variables and a
      configurational approach that focuses on use profiles. RESULTS: Five use profiles
      were identified, the largest of which (46.95% of encounters) described basic HIE
      access. ICU admission is more probable when the HIE system is perused by multiple
      users (odds increase by 31%) and when use profiles include prolonged screen
      viewing (odds increase by 159%) or access to diverse and multiple types of
      information, specifically on test results, procedures, and previous encounters.
      DISCUSSION: Reductionistic and configurational approaches yield complementary
      insights, which advance the understanding of how actual HIE use is associated
      with clinical decision making. The study shows that congruent profiles of HIE use
      enhance the predictability of the admission decision beyond what can be explained
      by independent variables of HIE use.

PMID- 26212127
TI  - Tunable Fermi level and hedgehog spin texture in gapped graphene.
AB  - Spin and pseudospin in graphene are known to interact under enhanced spin-orbit
      interaction giving rise to an in-plane Rashba spin texture. Here we show that Au
      intercalated graphene on Fe(110) displays a large (~230 meV) bandgap with out-of
      plane hedgehog-type spin reorientation around the gapped Dirac point. We identify
      two causes responsible. First, a giant Rashba effect (~70 meV splitting) away
      from the Dirac point and, second, the breaking of the six-fold graphene symmetry
      at the interface. This is demonstrated by a strong one-dimensional anisotropy of
      the graphene dispersion imposed by the two-fold-symmetric (110) substrate.
      Surprisingly, the graphene Fermi level is systematically tuned by the Au
      concentration and can be moved into the bandgap. We conclude that the out-of
      plane spin texture is not only of fundamental interest but can be tuned at the
      Fermi level as a model for electrical gating of spin in a spintronic device.

PMID- 26212126
TI  - Effect of interferon-beta1b on CXCR4-dependent chemotaxis in T cells from
      multiple sclerosis patients.
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating and neurodegenerative
      disease triggered by infiltration of activated T cells into the central nervous
      system. Interferon (IFN)-beta is an established, safe and effective treatment for
      patients with relapsing-remitting MS (RRMS). The cytokine can inhibit leucocyte
      infiltration into the central nervous system; however, little is known about the
      precise molecular mechanisms. Previously, in vitro application of IFN-beta1b was
      shown to reduce CXCL12/CXCR4-mediated monocyte migration. Here, we analysed the
      effects of IFN-beta1b on CXCR4-dependent T cell function. In vitro exposure to
      IFN-beta1b (1000 U/ml) for 20 h reduced CXCR4-dependent chemotaxis of primary
      human T cells from healthy individuals and patients with RRMS. Investigating the
      IFN-beta1b/CXCR4 signalling pathways, we found no difference in phosphorylation
      of ZAP70, ERK1/2 and AKT despite an early induction of the negative regulator of
      G-protein signalling, RGS1 by IFN-beta1b. However, CXCR4 surface expression was
      reduced. Quantitative real time-PCR revealed a similar reduction in CXCR4-mRNA,
      and the requirement of several hours' exposure to IFN-beta1b supports a
      transcriptional regulation. Interestingly, T cells from MS patients showed a
      lower CXCR4 expression than T cells from healthy controls, which was not reduced
      further in patients under IFN-beta1b therapy. Furthermore, we observed no change
      in CXCL12-dependent chemotaxis in RRMS patients. Our results demonstrate clearly
      that IFN-beta1b can impair the functional response to CXCR4 by down-regulating
      its expression, but also points to the complex in vivo effects of IFN-beta1b
      therapy. 

PMID- 26212128
TI  - Mitochondrial impairment and oxidative stress compromise autophagosomal
      degradation of alpha-synuclein in oligodendroglial cells.
AB  - alpha-Synuclein (alpha-syn)-containing glial cytoplasmic inclusions originating
      in oligodendrocytes are characteristically observed in multiple system atrophy.
      The mechanisms of glial cytoplasmic inclusion formation remain rather elusive.
      alpha-Syn over-expression, uptake from the environment, oxidative stress or
      impairment of the proteolytic degradation systems have been discussed. Here, we
      investigated whether in oligodendrocytes autophagy plays a major role in the
      degradation and aggregation of endogenously expressed alpha-syn and of alpha-syn
      taken up from the extracellular environment. Furthermore, we studied whether in
      cells with impaired mitochondria the accumulation and aggregation of exogenously
      added alpha-syn is promoted. Using primary cultures of rat brain oligodendrocytes
      and an oligodendroglial cell line, genetically engineered to express green
      fluorescent protein-microtubule-associated light chain 3 with or without alpha
      syn to monitor the autophagic flux, we demonstrate that both exogenously applied
      alpha-syn and alpha-syn stably expressed endogenously are effectively degraded by
      autophagy and do not affect the autophagic flux per se. Mitochondrial impairment
      with the protonophore carbonyl cyanide 3-chlorophenylhydrazone or 3
      nitropropionic acid disturbs the autophagic pathway and leads to the accumulation
      of exogenously applied alpha-syn and enhances its propensity to form aggregates
      intracellularly. Thus, mitochondrial dysfunction and oxidative stress, which
      occur over time and are significant pathological features in synucleinopathies,
      have an impact on the autophagic pathway and participate in pathogenesis. Glial
      cytoplasmic inclusions are characteristically observed in multiple system
      atrophy, their occurrence might be related to failure in protein degradation
      systems. Here, we show that in oligodendrocytes autophagy is the major route of
      alpha-synuclein degradation which is either endogenously expressed or added
      exogenously (1, 2). Mitochondrial impairment (3) disturbs the autophagic flux and
      leads to the accumulation of exogenously applied alpha-synuclein, and enhances
      its propensity to form aggregates intracellulary (4). 

PMID- 26212129
TI  - Systematic design of secondary building units by an efficient cation-directing
      strategy under regular vibrations of ionic liquids.
AB  - A cobalt-1,4-naphthalenedicarboxylic acid system in a systematic series of ionic
      liquids with different alkyl chain lengths of imidazolium cations governed the
      construction of four MOFs with regular changes of secondary building units
      (SBUs). 

PMID- 26212130
TI  - Design of a Kagome lattice from soft anisotropic particles.
AB  - We present a simple model of triblock Janus particles based on discoidal building
      blocks, which can form energetically stabilized Kagome structures. We find 'magic
      number' global minima in small clusters whenever particle numbers are compatible
      with a perfect Kagome structure, without constraining the accessible three
      dimensional configuration space. The preference for planar structures with two
      bonds per patch among all other possible minima on the landscape is enhanced when
      sedimentation forces are included. For the building blocks in question,
      structures containing three bonds per patch become progressively higher in energy
      compared to Kagome structures as sedimentation forces increase. Rearrangements
      between competing structures, as well as ring formation mechanisms are
      characterised and found to be highly cooperative. 

PMID- 26212131
TI  - Social Novelty Investigation in the Juvenile Rat: Modulation by the MU-Opioid
      System.
AB  - The drive to approach and explore novel conspecifics is inherent to social
      animals and may promote optimal social functioning. Juvenile animals seek out
      interactions with novel peers more frequently and find these interactions to be
      more rewarding than their adult counterparts. In the present study, we aimed to
      establish a behavioural paradigm to measure social novelty-seeking in juvenile
      rats and to determine the involvement of the opioid, dopamine, oxytocin and
      vasopressin systems in this behaviour. To this end, we developed the social
      novelty preference test to assess the preference of a juvenile rat to investigate
      a novel over a familiar (cage mate) conspecific. We show that across the juvenile
      period both male and female rats spend more time investigating a novel
      conspecific than a cage mate, independent of subject sex or repeated exposure to
      the test. We hypothesised that brain systems subserving social information
      processing and social motivation/reward (i.e. the opioid, dopamine, oxytocin,
      vasopressin systems) might support social novelty preference. To test this,
      receptor antagonists of each of these systems were administered i.c.v. prior to
      exposure to the social novelty preference test and, subsequently, to the social
      preference test, to examine the specificity of these effects. We find that MU
      opioid receptor antagonism reduces novel social investigation in both the social
      novelty preference and social preference tests while leaving the investigation of
      a cage mate (social novelty preference test) or an object (social preference
      test) unaffected. In contrast, central blockade of dopamine D2 receptors (with
      eticlopride), oxytocin receptors (with des-Gly-NH2,d(CH2)5[Tyr(Me)2,Thr4]OVT) or
      vasopressin V1a receptors [with (CH2)5Tyr(Me2)AVP] failed to alter social novelty
      preference or social preference. Overall, we have established a new behavioural
      test to study social novelty-seeking behaviour in the juvenile rat and show that
      the MU-opioid system facilitates this behaviour, possibly by reducing risk
      avoidance and enhancing the hedonic and/or motivational value of social novelty.

PMID- 26212132
TI  - Mental health implications for older adults after natural disasters--a systematic
      review and meta-analysis.
AB  - BACKGROUND: Natural disasters affect the health and well-being of adults
      throughout the world. There is some debate in the literature as to whether older
      persons have increased risk of mental health outcomes after exposure to natural
      disasters when compared with younger adults. To date, no systematic review has
      evaluated this. We aimed to synthesize the available evidence on the impact of
      natural disasters on the mental health and psychological distress experienced by
      older adults. DESIGN: A meta-analysis was conducted on papers identified through
      a systematic review. The primary outcomes measured were post-traumatic stress
      disorder (PTSD), depression, anxiety disorders, adjustment disorder, and
      psychological distress. RESULTS: We identified six papers with sufficient data
      for a random effects meta-analysis. Older adults were 2.11 times more likely to
      experience PTSD symptoms and 1.73 more likely to develop adjustment disorder when
      exposed to natural disasters when compared with younger adults. CONCLUSIONS:
      Given the global rise in the number of older adults affected by natural
      disasters, mental health services need to be prepared to meet their needs
      following natural disasters, particularly around the early detection and
      management of PTSD.

PMID- 26212133
TI  - Enzymatically Generated CRISPR Libraries for Genome Labeling and Screening.
AB  - CRISPR-based technologies have emerged as powerful tools to alter genomes and
      mark chromosomal loci, but an inexpensive method for generating large numbers of
      RNA guides for whole genome screening and labeling is lacking. Using a method
      that permits library construction from any source of DNA, we generated guide
      libraries that label repetitive loci or a single chromosomal locus in Xenopus egg
      extracts and show that a complex library can target the E. coli genome at high
      frequency. 

PMID- 26212134
TI  - RAD18 Is a Maternal Limiting Factor Silencing the UV-Dependent DNA Damage
      Checkpoint in Xenopus Embryos.
AB  - In early embryos, the DNA damage checkpoint is silent until the midblastula
      transition (MBT) because of maternal limiting factors of unknown identity. Here
      we identify the RAD18 ubiquitin ligase as one such factor in Xenopus. We show, in
      vitro and in vivo, that inactivation of RAD18 function leads to DNA damage
      dependent checkpoint activation, monitored by CHK1 phosphorylation. Moreover, we
      show that the abundance of both RAD18 and PCNA monoubiquitylated (mUb) are
      developmentally regulated. Increased DNA abundance limits the availability of
      RAD18 close to the MBT, thereby reducing PCNA(mUb) and inducing checkpoint
      derepression. Furthermore, we show that this embryonic-like regulation can be
      reactivated in somatic mammalian cells by ectopic RAD18 expression, therefore
      conferring resistance to DNA damage. Finally, we find high RAD18 expression in
      cancer stem cells highly resistant to DNA damage. Together, these data propose
      RAD18 as a critical embryonic checkpoint-inhibiting factor and suggest that RAD18
      deregulation may have unexpected oncogenic potential. 

PMID- 26212135
TI  - Cell Competition Modifies Adult Stem Cell and Tissue Population Dynamics in a JAK
      STAT-Dependent Manner.
AB  - Throughout their lifetime, cells may suffer insults that reduce their fitness and
      disrupt their function, and it is unclear how these potentially harmful cells are
      managed in adult tissues. We address this question using the adult Drosophila
      posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations
      to reduce fitness in groups of cells. We take a quantitative approach combining
      lineage tracing and biophysical modeling and address how cell competition affects
      stem cell and tissue population dynamics. We show that healthy cells induce
      clonal extinction in weak tissues, targeting both stem and differentiated cells
      for elimination. We also find that competition induces stem cell proliferation
      and self-renewal in healthy tissue, promoting selective advantage and tissue
      colonization. Finally, we show that winner cell proliferation is fueled by the
      JAK-STAT ligand Unpaired-3, produced by Minute(-/+) cells in response to chronic
      JNK stress signaling. 

PMID- 26212136
TI  - Protein Crowding Is a Determinant of Lipid Droplet Protein Composition.
AB  - Lipid droplets (LDs) are lipid storage organelles that grow or shrink, depending
      on the availability of metabolic energy. Proteins recruited to LDs mediate many
      metabolic functions, including phosphatidylcholine and triglyceride synthesis.
      How the LD protein composition is tuned to the supply and demand for lipids
      remains unclear. We show that LDs, in contrast to other organelles, have limited
      capacity for protein binding. Consequently, macromolecular crowding plays a major
      role in determining LD protein composition. During lipolysis, when LDs and their
      surfaces shrink, some, but not all, proteins become displaced. In vitro studies
      show that macromolecular crowding, rather than changes in monolayer lipid
      composition, causes proteins to fall off the LD surface. As predicted by a
      crowding model, proteins compete for binding to the surfaces of LDs. Moreover,
      the LD binding affinity determines protein localization during lipolysis. Our
      findings identify protein crowding as an important principle in determining LD
      protein composition. 

PMID- 26212137
TI  - Renal function during pregnancy may predict risk of future hospitalization due to
      atherosclerotic-related morbidity.
AB  - AIM: This study aims to examine whether renal function during pregnancy can serve
      as a surrogate marker for the risk of developing atherosclerotic-related
      morbidity. METHODS: A case-control study, including women who gave birth at a
      tertiary referral medical centre during 2000-2012. This population was divided
      into cases of women who were subsequently hospitalized for atherosclerotic
      morbidity during the study period and age-matched controls. From the study
      population, we retrieved two groups: the creatinine (Cr) group: women who had at
      least one Cr measurement (4945 women) and the urea group: women who had at least
      one urea measurement (4932 women) during their pregnancies. In the Cr and urea
      group, there were 572 and 571 cases and 4373 and 4361 controls, respectively. The
      mean follow-up period in the Cr and urea group was 61.7 +/- 37.0 and 57.3 +/-
      36.0 months, respectively. Cox proportional hazards models (controlling for
      confounders: gestational hypertension, gestational diabetes, obesity, maternal
      age, creatinine level (for urea), and gestational week) were used to estimate the
      adjusted hazard ratios (HR) for hospitalizations. RESULTS: A significant
      association was documented between renal function during pregnancy and long-term
      atherosclerotic morbidity. Multivariate analysis, showed that Cr at pregnancy
      index of >=89 MUmol/L was associated with a significant increased risk for
      hospitalization due to cardiovascular (CVS) events (adjusted HR = 2.91 CI 1.37
      6.19 P = 0.005) and urea level <=7 mmol/L was independently associated with
      reduced prevalence of CVS hospitalization (adjusted HR = 0.62 CI 0.57-0.86 P =
      0.001). CONCLUSION: Renal function abnormality during pregnancy may reveal occult
      predisposition to atherosclerotic morbidity years after childbirth.

PMID- 26212138
TI  - Dysregulation of Hypothalamo-Pituitary-Adrenocortical Axis in Overweight Female
      Diabetic Subjects is Associated with Downregulation of Corticosteroid Receptors
      and 11beta-HSD1 in the Brain.
AB  - The objective of this work was to assess hypothalamo-pituitary-adrenocortical
      (HPA) axis dysregulation in overweight diabetic women and investigate the
      possible mechanism using overweight diabetic rats. Twenty-two overweight diabetic
      women were recruited alongside 34 lean and 23 overweight healthy women serving as
      controls. Dexamethasone suppression test (0.25 mg DST) and low dose
      adrenocorticotropic hormone (ACTH) stimulation assay were used to evaluate the
      HPA axis activity. Then, high fat diet (HF) and STZ-induced diabetic rats were
      utilized to investigate the possible mechanism. After measurement of
      corticosterone circadian patterns and dexamethasone suppression levels, mRNA
      amounts of mineralocorticoid receptors (MR), glucocorticoid receptors (GR), and
      11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) were determined by real
      time PCR at hippocampus, hypothalamus, and pituitary levels. Overweight diabetic
      women showed impaired HPA axis with negative feedback efficacy (suppression ratio
      F-DEX%: 0.52+/-0.06% vs. 0.49+/-0.06% vs. 0.14+/-0.08%), as well as increased
      adrenal cortisol secretion response to low dose ACTH stimulation. Interestingly,
      F-DEX% was negatively correlated with BMI (r=- 0.323, p=0.003), waist
      circumference (r=- 0.319, p=0.004), and HbA1c (r=- 0.334, p=0.002). Stepwise
      linear regression analysis showed F-DEX% was significantly related to HbA1c level
      (beta=- 0.328, p=0.007) after adjusting for other covariates (age, BMI, waist
      circumference, SBP, TC, TG, and HOMA-IR). Furthermore, 11beta-HSD1, MR, and GR
      mRNA expression levels were reduced at pituitary level while GR expression was
      downregulated at hippocampus level in HF and HF+STZ rats. In conclusion,
      hyperactive HPA axis in overweight diabetic subjects may be associated with
      downregulation of 11beta-HSD1, MR, and GR in the brain. 

PMID- 26212139
TI  - Development and Efficacy Assessment of an Enteric Coated Porous Tablet Loaded
      With F4 Fimbriae for Oral Vaccination of Piglets against F4+ Escherichia coli
      Infections.
AB  - Enterotoxigenic Escherichia coli (ETEC) infection is one of the major causes
      contributing to the development of diarrhoea and mortality in new born, suckling
      and newly weaned piglets. To date, no preventive/treatment strategy showed
      promising results, which could be due to the lack of potent vaccines, and/or due
      to the development of resistance of ETEC to antibiotics. Therefore, in the
      present investigation, a novel porous sodium alginate (SA) tablet formulation
      loaded with F4 fimbriae antigen was developed and tested for efficacy against
      ETEC infections in piglet models. Precompression parameters of the powder mixes
      and post compression parameters of tablets have been evaluated and results were
      found to be satisfactory. Loading of F4 fimbrial antigens into the tablets was
      achieved by inducing pores in the tablets via the sublimation of camphor followed
      by incubation with purified F4 fimbriae. The loaded tablets have been coated with
      Eudragit L100 to protect the F4 fimbriae from (a) highly acidic gastric
      environment; (b) proteolytic cleavage by pepsin; and (c) to promote subsequent
      release in the intestine. Evaluation of developed F4 fimbrial tablets in a Pig
      model demonstrated induction of mucosal immunity, and a significant reduction of
      F4+ E. coli in faeces. Therefore, F4 fimbriae loaded porous tablets could be a
      novel oral vaccination candidate to induce mucosal and systemic immunity against
      ETEC infections. 

PMID- 26212140
TI  - Targeted vaccination of teenagers following continued rapid endemic expansion of
      a single meningococcal group W clone (sequence type 11 clonal complex), United
      Kingdom 2015.
AB  - Since the epidemiological year 2009/10, the United Kingdom has experienced a year
      on-year increase in meningococcal group W (MenW) disease due to rapid expansion
      of a single endemic hyper-virulent strain belonging to sequence type 11 clonal
      complex (cc). This strain was identified among cases diagnosed across all regions
      and was not linked to travel abroad. Consequently, an adolescent MenACWY
      conjugate vaccination programme for 13-18 year-olds will be introduced in August
      2015, with priority given to 17-18 year-olds (school leavers).

PMID- 26212141
TI  - Evaluation of immunochromatography tests for detection of novel GII.17 norovirus
      in stool samples.
AB  - A novel GII.17 norovirus has emerged as a major cause of epidemic and endemic
      acute gastroenteritis in several countries in Asia. We used a small panel of
      stool samples in which GII.17 virus had been quantified by real-time RT-PCR to
      evaluate four commercially available norovirus immunochromatography (IC) kits. At
      least 10(8) copies/mL of GII.17 virus were required by each IC kit for a positive
      result, which is 1,000-fold more than that reported for these assays for GII.4
      viruses.

PMID- 26212142
TI  - Design and application of a core genome multilocus sequence typing scheme for
      investigation of Legionnaires' disease incidents.
AB  - Sequence-based typing (SBT) for Legionella pneumophila (Lp) has dramatically
      improved Legionnaires' disease (LD) cluster investigation. Microbial whole genome
      sequencing (WGS) is a promising modality for investigation but sequence analysis
      methods are neither standardised, nor agreed. We sought to develop a WGS-based
      typing scheme for Lp using de novo assembly and a genome-wide gene-by-gene
      approach (core genome multilocus sequence typing, cgMLST). We analysed 17
      publicly available Lp genomes covering the whole species variation to define a
      core genome (1,521 gene targets) which was validated using 21 additional
      published genomes. The genomes of 12 Lp strains implicated in three independent
      cases of paediatric humidifier-associated LD were subject to cgMLST together with
      three 'outgroup' strains. cgMLST was able to resolve clustered strains and
      clearly identify related and unrelated strains. Thus, a cgMLST scheme was readily
      achievable and provided high-resolution analysis of Lp strains. cgMLST appears to
      have satisfactory discriminatory power for LD cluster analysis and is
      advantageous over mapping followed by single nucleotide polymorphism (SNP)
      calling as it is portable and easier to standardise. cgMLST thus has the
      potential for becoming a gold standard tool for LD investigation. Humidifiers
      pose an ongoing risk as vehicles for LD and should be considered in cluster
      investigation and control efforts.

PMID- 26212143
TI  - Improving national surveillance of Lyme neuroborreliosis in Denmark through
      electronic reporting of specific antibody index testing from 2010 to 2012.
AB  - Our aim was to evaluate the results of automated surveillance of Lyme
      neuroborreliosis (LNB) in Denmark using the national microbiology database
      (MiBa), and to describe the epidemiology of laboratory-confirmed LNB at a
      national level. MiBa-based surveillance includes electronic transfer of
      laboratory results, in contrast to the statutory surveillance based on manually
      processed notifications. Antibody index (AI) testing is the recommend laboratory
      test to support the diagnosis of LNB in Denmark. In the period from 2010 to 2012,
      217 clinical cases of LNB were notified to the statutory surveillance system,
      while 533 cases were reported AI positive by the MiBa system. Thirty-five
      unconfirmed cases (29 AI-negative and 6 not tested) were notified, but not
      captured by MiBa. Using MiBa, the number of reported cases was increased almost
      2.5 times. Furthermore, the reporting was timelier (median lag time: 6 vs 58
      days). Average annual incidence of AI-confirmed LNB in Denmark was 3.2/100,000
      population and incidences stratified by municipality ranged from none to above
      10/100,000. This is the first study reporting nationwide incidence of LNB using
      objective laboratory criteria. Laboratory-based surveillance with electronic data
      transfer was more accurate, complete and timely compared to the surveillance
      based on manually processed notifications. We propose using AI test results for
      LNB surveillance instead of clinical reporting.

PMID- 26212144
TI  - Estimating influenza vaccine effectiveness in Spain using sentinel surveillance
      data.
AB  - We aimed to estimate influenza vaccine effectiveness (VE) against laboratory
      confirmed influenza during three influenza seasons (2010/11 to 2012/2013) in
      Spain using surveillance data and to compare the results with data obtained by
      the cycEVA study, the Spanish component of the Influenza Monitoring Vaccine
      Effectiveness (I-MOVE) network. We used the test-negative case-control design,
      with data from the Spanish Influenza Sentinel Surveillance System (SISS) or from
      the cycEVA study. Cases were laboratory-confirmed influenza patients with the
      predominant influenza virus of each season, and controls were those testing
      negative for any influenza virus. We calculated the overall and age-specific
      adjusted VE. Although the number of patients recorded in the SISS was three times
      higher than that in the cycEVA study, the quality of information for important
      variables, i.e. vaccination status and laboratory results, was high in both
      studies. Overall, the SISS and cycEVA influenza VE estimates were largely similar
      during the study period. For elderly patients (> 59 years), the SISS estimates
      were slightly lower than those of cycEVA, and estimates for children (0-14 years)
      were higher using SISS in two of the three seasons studied. Enhancing the SISS by
      collecting the date of influenza vaccination and reducing the percentage of
      patients with incomplete information would optimise the system to provide
      reliable annual influenza VE estimates to guide influenza vaccination policies.

PMID- 26212145
TI  - Melanoma and naevi with a globular pattern: confocal microscopy as an aid for
      diagnostic differentiation.
AB  - BACKGROUND: Dermoscopically, one of the most common findings in melanocytic
      lesions is a globular pattern. A regular globular pattern is a common finding in
      naevi. Melanoma can also show a globular pattern, with globules typically
      irregular in size, colour and distribution. OBJECTIVES: To investigate the
      likelihood of diagnosing melanoma according to distinct dermoscopic and confocal
      aspects. METHODS: Dermoscopic and confocal aspects of 83 excised melanocytic
      lesions dermoscopically showing globules were analysed. RESULTS: Our study
      population included 39 acquired melanocytic naevi, 16 Spitz naevi and 28
      melanomas. Univariate analysis showed that regular distribution of globules on
      dermoscopy is associated with a ninefold lower risk for melanoma, whereas an
      irregular distribution is associated with an almost 10-fold increased risk for
      melanoma. Concerning confocal features, dense nests are associated with a
      fivefold lower risk for melanoma, whereas loosely arranged nests are associated
      with an almost sixfold risk for melanoma; moreover, the presence of round cells
      is associated with a 17-fold lower risk for melanoma, whereas pleomorphic cells
      are associated with an almost 16-fold risk for melanoma. CONCLUSIONS: So that
      melanoma is not missed, clinicians should carefully analyse globular lesions in
      adults, focusing, in particular, on the distribution of globules and on the
      presence of confocal cytological atypia.

PMID- 26212146
TI  - Test-retest reliability of graph metrics in high-resolution functional
      connectomics: a resting-state functional MRI study.
AB  - BACKGROUND: The combination of resting-state functional MRI (R-fMRI) technique
      and graph theoretical approaches has emerged as a promising tool for
      characterizing the topological organization of brain networks, that is,
      functional connectomics. In particular, the construction and analysis of high
      resolution brain connectomics at a voxel scale are important because they do not
      require prior regional parcellations and provide finer spatial information about
      brain connectivity. However, the test-retest reliability of voxel-based
      functional connectomics remains largely unclear. AIMS: This study tended to
      investigate both short-term (~20 min apart) and long-term (6 weeks apart) test
      retest (TRT) reliability of graph metrics of voxel-based brain networks. METHODS:
      Based on graph theoretical approaches, we analyzed R-fMRI data from 53 young
      healthy adults who completed two scanning sessions (session 1 included two scans
      20 min apart; session 2 included one scan that was performed after an interval of
      ~6 weeks). RESULTS: The high-resolution networks exhibited prominent small-world
      and modular properties and included functional hubs mainly located at the default
      mode, salience, and executive control systems. Further analysis revealed that
      test-retest reliabilities of network metrics were sensitive to the scanning
      orders and intervals, with fair to excellent long-term reliability between Scan 1
      and Scan 3 and lower reliability involving Scan 2. In the long-term case (Scan 1
      and Scan 3), most network metrics were generally test-retest reliable, with the
      highest reliability in global metrics in the clustering coefficient and in the
      nodal metrics in nodal degree and efficiency. CONCLUSION: We showed high test
      retest reliability for graph properties in the high-resolution functional
      connectomics, which provides important guidance for choosing reliable network
      metrics and analysis strategies in future studies.

PMID- 26212147
TI  - Stabilization of Insulin by Adsorption on a Hydrophobic Silane Self-Assembled
      Monolayer.
AB  - The interaction between many proteins and hydrophobic functionalized surfaces is
      known to induce beta-sheet and amyloid fibril formation. In particular, insulin
      has served as a model peptide to understand such fibrillation, but the early
      stages of insulin misfolding and the influence of the surface have not been
      followed in detail under the acidic conditions relevant to the synthesis and
      purification of insulin. Here we compare the adsorption of human insulin on a
      hydrophobic (-CH3-terminated) silane self-assembled monolayer to a hydrophilic (
      NH3(+)-terminated) layer. We monitor the secondary structure of insulin with
      Fourier transform infrared attenuated total reflection and side-chain orientation
      with sum frequency spectroscopy. Adsorbed insulin retains a close-to-native
      secondary structure on both hydrophobic and hydrophilic surfaces for extended
      periods at room temperature and converts to a beta-sheet-rich structure only at
      elevated temperature. We propose that the known acid stabilization of human
      insulin and the protection of the aggregation-prone hydrophobic domains on the
      insulin monomer by adsorption on the hydrophobic surface work together to inhibit
      fibril formation at room temperature. 

PMID- 26212148
TI  - Physiological responses of the ghost shrimp Neotrypaea uncinata (Milne Edwards
      1837) (Decapoda: Thalassinidea) to oxygen availability and recovery after severe
      environmental hypoxia.
AB  - Hypoxia is a common and widespread phenomenon in aquatic ecosystems, imposing a
      significant challenge for the animals that inhabit such waters. In different
      habitats, however, the characteristics of these hypoxic events may differ,
      therefore imposing different challenges. We investigated the tolerance of adult
      ghost shrimp Neotrypaea uncinata (an intertidal mudflat dweller) to different
      partial pressures of oxygen (pO2), severe hypoxia (2 kPa) and recovery from
      hypoxia after different exposure times, mimicking the natural tidal cycle (6 h
      and 12 h). We calculated critical oxygen tension and categorize the adult ghost
      shrimps as oxyregulators (R value=75.27%). All physiological measurements
      (metabolic rate, oxyhemocyanin, hemolymph protein and lactate concentrations)
      were affected by exposure to low partial pressures of oxygen, but most of them
      recovered (with exception of metabolic rate) control values (21 kPa) after 6h
      under normoxic conditions. Low metabolic rate, high release of hemolymphatic
      proteins and anaerobic metabolism are suggested as response mechanisms to
      overcome hypoxic events during low tide.

PMID- 26212149
TI  - Poly(ADP-ribose) polymerase inhibitor therapeutic effect: are we just scratching
      the surface?
AB  - Poly(ADP-ribose) polymerase (PARP) research has come a long way since the
      discovery of the enzyme 50 years ago. Since the development of first-generation
      PARP inhibitors (PARPi), numerous clinical trials have been performed to validate
      their safety and efficacy, bringing us to the stage at which a PARPi is now a
      valuable treatment option for patients with ovarian cancer. Nevertheless, the
      exact molecular mechanism of the PARPi anti-tumor effect is under debate and
      PARPi are not specific for a single enzyme. Moreover, the anti-inflammatory
      activity of PARPi in preclinical experiments has not been explored much so far.
      Thus, further basic and preclinical research is needed to advance the use of
      PARPi in the treatment of tumors and potentially other inflammation-associated
      diseases. 

PMID- 26212150
TI  - Immature T cell neoplasms in three young cattle.
AB  - Immature T cell neoplasms in three young Holstein cattle with neoplastic
      involvement of the thymus are described. Case 1, with a precursor T lymphoblastic
      leukemia (calf form of leukosis), was an 86-day-old female calf. The leukemia was
      characterized by replacement of the bone marrow and spleen by leukemia cells, but
      preservation of epithelial frameworks throughout the thymus. The other two
      neoplasms were thymic gammadelta T cell lymphomas, which were observed in a 246
      day-old steer (case 2) and a 16-month-old heifer (case 3). Histological
      examination revealed obliteration of the normal thymic architecture and stromal
      fibrosis, with the spleen and liver far less severely affected than in case 1.
      There were cytological differences bewteen the tumors in case 1 and cases 2 and
      3. Additionally, WC1 and CD8 were expressed only in the latter. Thus, the
      leukemia and these lymphomas should be regarded as independent disease entities
      on the basis of histological and immunohistochemical characteristics. 

PMID- 26212151
TI  - Submacular hemorrhage in neovascular age-related macular degeneration: A
      synthesis of the literature.
AB  - Large submacular hemorrhage, an uncommon manifestation of neovascular age-related
      macular degeneration, may also occur with idiopathic polypoidal choroidal
      vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron
      toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent
      macular scarring. Clinical and experimental studies support prompt treatment, as
      tissue damage can occur within 24 hours. Without treatment the natural history is
      poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments
      include retinal pigment epithelial patch, macular translocation, pneumatic
      displacement, intravitreal or subretinal tissue plasminogen activator,
      intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and
      combinations thereof. In the absence of comparative studies, we combined eligible
      studies to assess the VA change before and after each treatment option. The
      greatest improvement occurred after combined pars plana vitrectomy, subretinal
      tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial
      growth factor treatment, with VA improving from 20/1000 to 20/400. The best final
      VA occurred using combined intravitreal tissue plasminogen activator, gas, and
      anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to
      20/100. Both treatments had an acceptable safety profile, but most studies were
      small, and larger randomized controlled trials are needed to determine both
      safety and efficacy.

PMID- 26212152
TI  - What's in a name?
AB  - A 51-year-old man with rheumatoid arthritis and diabetes mellitus presented with
      new onset left-sided hemiparesis, left-sided neglect, and left-sided incongruous,
      denser inferiorly, homonymous hemianopsia. Magnetic resonance image of the brain
      showed prominent swelling of the right frontal, parietal, and occipital lobes
      greater than on the left with significant change in the fluid-attenuated
      inversion recovery signal in the gray matter. Perinuclear antineutrophil
      cytoplasmic antibodies titers were elevated, and skin biopsy demonstrating
      leukocytoclastic vasculitis. He showed marked clinical and radiographic
      improvement in association with recovery of vascular abnormalities after the
      initiation of prednisone, pulse therapy with methylprednisolone, and
      methotrexate. Clinicians should be aware of the possibility of neuro-ophthalmic
      manifestations of rheumatoid arthritis, including rheumatoid arthritis-related
      vasculitis causing homonymous hemianopsia. 

PMID- 26212153
TI  - The need for histological subclassification of cirrhosis: a systematic review and
      meta-analysis.
AB  - BACKGROUND & AIMS: The need for further histological subclassification of
      cirrhosis has been increasingly recognized because of the heterogeneity of
      severity within cirrhosis. We sought to identify evidence in the literature
      regarding the histological subclassification of cirrhosis using the Laennec
      stage. METHODS: We conducted a systematic review and meta-analysis by searching
      databases, including MEDLINE, EMBASE and the COCHRANE library, for relevant
      studies. RESULTS: Of 208 studies identified, 16 were eligible according to the
      inclusion criteria. With higher grades of the Laennec stage, clinical stages of
      cirrhosis and Child-Pugh scores/Model for end-stage liver disease scores
      increased (P < 0.05). Higher Laennec stages were statistically associated with
      the development of liver-related events, such as liver-related death, liver
      cancer progression and variceal haemorrhage, as well as higher hepatic venous
      pressure gradients and higher liver stiffness values (P < 0.05). Two open
      labelled studies showed the usefulness of the Laennec system with regard to the
      evaluation of whether antifibrotic treatments were effective. The mean kappa
      value was 0.81 (range 0.61-0.87) for inter-observer agreement. CONCLUSIONS: Based
      on this systematic review and meta-analysis, histological subclassification of
      cirrhosis using the Laennec system is useful to better predict prognosis and
      complications of portal hypertension.

PMID- 26212154
TI  - Factors associated with contraceptive use and intention to use contraceptives
      among married women in Ethiopia.
AB  - Family planning has improved the well-being of families by preventing high-risk
      pregnancies and abortions and reducing unplanned pregnancies. However, the
      effectiveness of family planning efforts has not been consistent across
      countries. This study examined factors associated with contraceptive use among
      married women in Ethiopia. Data were from the 2011 Ethiopian Demographic and
      Health Survey. The sample comprised 10,204 married women (aged 15-49 years).
      Logistic regression models were used to analyze the data. Among married women in
      Ethiopia, 29.2% used contraceptive methods. About 44.1% of women who were not
      current users of contraceptives reported that they intended to use contraceptives
      in the future. Age at first marriage, being educated, number of living children,
      exposure to mass media, being employed, having educated partners, and having been
      informed about contraceptive use at health facilities were positively associated
      with current contraceptive use. By contrast, older age, a rural resident, or
      Muslim; belonging to the Afar or Somali ethnic groups; desiring numerous
      children; having husbands who desired additional children; and abortion
      experience were negatively associated with current contraceptive use. Our
      findings indicated that improving education, providing employment opportunities
      for women, and providing training to family planning providers are essential to
      increasing contraceptive use. 

PMID- 26212155
TI  - Lay epidemiology and the interpretation of low-risk drinking guidelines by adults
      in the United Kingdom.
AB  - AIMS: To explore how the concept of lay epidemiology can enhance understandings
      of how drinkers make sense of current UK drinking guidelines. METHODS:
      Qualitative study using 12 focus groups in four sites in northern England and
      four sites in central Scotland. Participants were 66 male and female drinkers,
      aged between 19 and 65 years, of different socio-economic backgrounds. Data were
      analysed thematically using a conceptual framework of lay epidemiology. RESULTS:
      Current drinking guidelines were perceived as having little relevance to
      participants' drinking behaviours and were generally disregarded. Daily
      guidelines were seen as irrelevant by drinkers whose drinking patterns comprised
      heavy weekend drinking. The amounts given in the guidelines were seen as
      unrealistic for those motivated to drink for intoxication, and participants
      measured alcohol intake in numbers of drinks or containers rather than units.
      Participants reported moderating their drinking, but this was out of a desire to
      fulfil work and family responsibilities, rather than concerns for their own
      health. The current Australian and Canadian guidelines were preferred to UK
      guidelines, as they were seen to address many of the above problems. CONCLUSIONS:
      Drinking guidelines derived from, and framed within, solely epidemiological
      paradigms lack relevance for adult drinkers who monitor and moderate their
      alcohol intake according to their own knowledge and risk perceptions derived
      primarily from experience. Insights from lay epidemiology into how drinkers
      regulate and monitor their drinking should be used in the construction of
      drinking guidelines to enhance their credibility and efficacy.

PMID- 26212157
TI  - Preclinical testing of drug delivery systems to bone.
AB  - Bone defects do not heal in 5-10% of the fractures. In order to enhance bone
      regeneration, drug delivery systems are needed. They comprise a scaffold with or
      without inducing factors and/or cells. To test these drug delivery systems before
      application in patients, they finally need to be tested in animal models. The
      choice of animal model depends on the main research question; is a functional or
      mechanistic evaluation needed? Furthermore, which type of bone defects are
      investigated: load-bearing (i.e. orthopedic) or non-load-bearing (i.e.
      craniomaxillofacial)? This determines the type of model and in which type of
      animal. The experiments need to be set-up using the 3R principle and must be
      reported following the ARRIVE guidelines. 

PMID- 26212156
TI  - Tissue engineering the cardiac microenvironment: Multicellular microphysiological
      systems for drug screening.
AB  - The ability to accurately detect cardiotoxicity has become increasingly important
      in the development of new drugs. Since the advent of human pluripotent stem cell
      derived cardiomyocytes, researchers have explored their use in creating an in
      vitro drug screening platform. Recently, there has been increasing interest in
      creating 3D microphysiological models of the heart as a tool to detect
      cardiotoxic compounds. By recapitulating the complex microenvironment that exists
      in the native heart, cardiac microphysiological systems have the potential to
      provide a more accurate pharmacological response compared to current standards in
      preclinical drug screening. This review aims to provide an overview on the
      progress made in creating advanced models of the human heart, including the
      significance and contributions of the various cellular and extracellular
      components to cardiac function. 

PMID- 26212158
TI  - Hydrogels for therapeutic cardiovascular angiogenesis.
AB  - Acute myocardial infarction (MI) caused by ischemia is the most common cause of
      cardiac dysfunction. While growth factor or cell therapy is promising, the
      retention of bioactive agents in the highly vascularized myocardium is limited
      and prevents sustained activation needed for adequate cellular responses. Various
      types of biomaterials with different physical and chemical properties have been
      developed to improve the localized delivery of growth factor and/or cells for
      therapeutic angiogenesis in ischemic tissues. Hydrogels are particularly
      advantageous as carrier systems because they are structurally similar to the
      tissue extracellular matrix (ECM), they can be processed under relatively mild
      conditions and can be delivered in a minimally invasive manner. Moreover,
      hydrogels can be designed to degrade in a timely fashion that coincides with the
      angiogenic process. For these reasons, hydrogels have shown great potential as
      pro-angiogenic matrices. This paper reviews a few of the hydrogel systems
      currently being applied together with growth factor delivery and/or cell therapy
      to promote therapeutic angiogenesis in ischemic tissues, with emphasis on
      myocardial applications. 

PMID- 26212159
TI  - Mechanical regulation of vascular network formation in engineered matrices.
AB  - Generation of vessel networks within engineered tissues is critical for
      integration and perfusion of the implanted tissue in vivo. The effect of
      mechanical cues in guiding and stabilizing the vessels has begun to attract
      marked interest. This review surveys the impact of mechanical cues on formation
      of vascular networks in 2D and 3D gel matrices. We give less emphasis to
      regulation of endothelial monolayers and single endothelial cells. Several
      vascularization models have consistently found that the stress generated in the
      gel, and encountered by embedded cells, control various aspects of vascular
      network formation, including sprouting, branching, alignment, and vessel
      maturation. This internal stress is generated by cell contractile forces, and is
      balanced by gel stiffness and boundary constrains imposed on the gel. Actin and
      myosin II are key molecular players in controlling initiation of vessel sprouting
      and branching morphogenesis. Additionally, the impact of external mechanical cues
      on tissue vascularization, and studies supporting the notion that mechanical
      forces regulate vascularization in the live animal are reviewed. 

PMID- 26212160
TI  - Rb-Sr resonance ionization geochronology of the Duluth Gabbro: A proof of concept
      for in situ dating on the Moon.
AB  - RATIONALE: We report new (87) Rb-(87) Sr isochron data for the Duluth Gabbro,
      obtained with a laser ablation resonance ionization mass spectrometer that is a
      prototype spaceflight instrument. The gabbro has a Rb abundance and a range of
      Rb/Sr ratios that are similar to those of KREEP-rich basalts found on the
      nearside of the Moon. Dating of previously un-sampled young lunar basalts, which
      generally have a KREEP-rich composition, is critical for understanding the
      bombardment history of the Moon since 3.5 Ga, which in turn informs the
      chronology of the solar system. Measurements of lunar analogs like the Duluth
      Gabbro are a proof of concept for in situ dating of rocks on the Moon to
      constrain lunar history. METHODS: Using the laser ablation resonance ionization
      mass spectrometer we ablated hundreds of locations on a sample, and at each one
      measured the relative abundances of the isotopes of Rb and Sr. A delay between
      the resonant photoionization processes separates the elements in time,
      eliminating the potential interference between (87) Rb and (87) Sr. This enables
      the determination of (87) Rb-(87) Sr isochron ages without sophisticated sample
      preparation that would be impractical in a spaceflight context. RESULTS: We
      successfully dated the Duluth Gabbro to 800 +/- 300 Ma using traditional isochron
      methods like those used in our earlier analysis of the Martian meteorite Zagami.
      However, we were able to improve this to 1100 +/- 200 Ma, an accuracy of <1sigma,
      using a novel normalization approach. Both these results agree with the age
      determined by Faure et al. in 1969, but our novel normalization improves our
      precision. CONCLUSIONS: Demonstrating that this technique can be used for
      measurements at this level of difficulty makes ~32% of the lunar nearside
      amenable to in situ dating, which can complement or supplement a sample return
      program. Given these results and the scientific value of dating young lunar
      basalts, we have recently proposed a spaceflight mission called the Moon Age and
      Regolith Explorer (MARE).

PMID- 26212161
TI  - Stable isotope composition (delta(13)C and delta(15)N values) of slime molds:
      placing bacterivorous soil protozoans in the food web context.
AB  - RATIONALE: Data on the bulk stable isotope composition of soil bacteria and
      bacterivorous soil animals are required to estimate the nutrient and energy
      fluxes via bacterial channels within detrital food webs. We measured the isotopic
      composition of slime molds (Myxogastria, Amoebozoa), a group of soil protozoans
      forming macroscopic spore-bearing fruiting bodies. An analysis of largely
      bacterivorous slime molds can provide information on the bulk stable isotope
      composition of soil bacteria. METHODS: Fruiting bodies of slime molds were
      collected in a monsoon tropical forest of Cat Tien National Park, Vietnam, and
      analyzed by continuous-flow isotope ratio mass spectrometry. Prior to stable
      isotope analysis, carbonates were removed from a subset of samples by
      acidification. To estimate the trophic position of slime molds, their delta(13) C
      and delta(15) N values were compared with those of plant debris, soil, microbial
      destructors (litter-decomposing, humus-decomposing, and ectomycorrhizal fungi)
      and members of higher trophic levels (oribatid mites, termites, predatory
      macroinvertebrates). RESULTS: Eight species of slime molds represented by at
      least three independent samples were 3-60/00 enriched in (13) C and (15) N
      relative to plant litter. A small but significant difference in the delta(13) C
      and delta(15) N values suggests that different species of myxomycetes can differ
      in feeding behavior. The slime molds were enriched in (15) N compared with litter
      decomposing fungi, and depleted in (15) N compared with mycorrhizal or humus
      decomposing fungi. Slime mold sporocarps and plasmodia largely overlapped with
      oribatid mites in the isotopic bi-plot, but were depleted in (15) N compared with
      predatory invertebrates and humiphagous termites. CONCLUSIONS: A comparison with
      reference groups of soil organisms suggests strong trophic links of slime molds
      to saprotrophic microorganisms which decompose plant litter, but not to humus
      decomposing microorganisms or to mycorrhizal fungi. Under the assumption that
      slime molds are primarily feeding on bacteria, the isotopic similarity of slime
      molds and mycophagous soil animals indicates that saprotrophic soil bacteria and
      fungi are similar in bulk isotopic composition.

PMID- 26212162
TI  - Derivatization of bisphenol A and its analogues with pyridine-3-sulfonyl
      chloride: multivariate optimization and fragmentation patterns by liquid
      chromatography/Orbitrap mass spectrometry.
AB  - RATIONALE: Due to the growing restrictions on the use of bisphenol A (BPA),
      several other bisphenols are gaining importance as substitutes for BPA in a
      variety of applications. There is, therefore, a real need for selective and
      sensitive methods based on mass spectrometry which will allow the human exposure
      to these new bisphenols to be assessed. METHODS: Derivatization of BPA and its
      substitutes with pyridine-3-sulfonyl chloride is used to enhance the detection
      capability of bisphenols by electrospray ionization mass spectrometry. A
      multivariate experimental design, Box-Behnken response surface, was used to
      evaluate the influence of the main variables potentially affecting the
      derivatization yield. Fragmentation patterns for all the derivatized bisphenols
      were acquired by high-resolution/accurate-mass Orbitrap mass spectrometry.
      RESULTS: Temperature and pH were identified as the most important factors
      affecting the derivatization yield of bisphenols. Fragmentation of the protonated
      molecules produced abundant analyte-specific product ions. Most of the
      derivatized bisphenols showed significant improvements in their signal-to-noise
      ratios compared with the underivatized forms. The stability of these derivatives
      was demonstrated through several freeze/thaw cycles, short-term room temperature
      and long-term cold storage. CONCLUSIONS: Derivatization of BPA and its structural
      analogues with pyridine-3-sulfonyl chloride is proposed as a specific, sensitive,
      high-throughput approach to their analysis by liquid chromatography coupled to
      electrospray ionization mass spectrometry.

PMID- 26212163
TI  - Milk isotopic values demonstrate that nursing fur seal pups are a full trophic
      level higher than their mothers.
AB  - RATIONALE: In mammals including humans, mother-to-offspring transfer of nutrients
      has been the focus of several isotopic studies. Measurement of delta(13) C and
      delta(15) N values were mainly conducted on easily sampled tissues such as blood
      and hair that allow the calculation of apparent discrimination factors (?(13) C
      and ?(15) N) between offspring and maternal tissues. Quantifying real ?(13) C and
      ?(15) N values requires the measurement of the delta(13) C and delta(15) N values
      of milk, the exclusive food of newborns. Surprisingly, little isotopic
      information is available on milk and its biochemical components (lipids and
      proteins). METHODS: Paired blood and milk samples from 10 lactating females and
      their pups were collected from two otariid species, the Antarctic and
      subantarctic fur seals. Tissue delta(13) C and delta(15) N values were measured
      using continuous-flow isotope ratio mass spectrometry (CFIRMS) on maternal and
      offspring blood, and on whole milk, lipid-free milk and milk lipids, thus
      allowing the calculation and comparison of apparent (maternal blood to offspring
      blood) and real (lipid-free milk to offspring blood) ?(13) C and ?(15) N values.
      RESULTS: In both fur seal species, the apparent ?(13) C values averaged ~0.0
      0/00. Lipid-free milk was slightly (13) C-depleted compared with both maternal
      and pup blood and it was strongly (13) C-enriched (~6.3 0/00) compared with milk
      lipids. In contrast, the apparent and real ?(15) N values averaged 1.2-1.4 and
      2.6-3.0 0/00, respectively, the differences being explained by the ~1.5 0/00
      lower milk delta(15) N values than those of maternal blood. CONCLUSIONS: In fur
      seals, the low apparent ?(15) N translated into a higher real ?(15) N value,
      amounting to a full trophic level, which is in agreement with the almost never
      verified hypothesis that (15) N differences between mothers and their offsprings
      should reflect one complete trophic level. The study highlights the need to
      measure milk isotopic values to disentangle the nutritional mother-to-offspring
      relationships.

PMID- 26212164
TI  - Lipidomic analysis of p-chlorophenylalanine-treated mice using continuous-flow
      two-dimensional liquid chromatography/quadrupole time-of-flight mass
      spectrometry.
AB  - RATIONALE: Although serotonin deficiency is involved with various physiological
      disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia and
      depression, the serotonin-dependent pathomechanisms remain poorly understood,
      particularly from a lipidomics perspective. METHODS: This study therefore aimed
      to identify novel lipid biomarkers associated with serotonin deficiency by lipid
      profiling of p-chlorophenylalanine (pCPA)-treated, serotonin-deficient mice using
      continuous-flow normal-phase/reversed-phase two-dimensional liquid
      chromatography/quadrupole time-of-flight mass spectrometry (NP/RP 2D LC/QTOFMS).
      Principal component analysis (PCA) was performed to distinguish significantly
      altered lipids between the pCPA-treated mice and control mice. RESULTS: Eighteen
      lipid biomarkers were associated with pCPA-induced serotonin deficiency.
      Specifically, lipid species of lysophosphatidylethanolamine (LPE),
      phosphatidylethanolamine (PE), sphingomyelin (SM), galactosylceramide (GalCer),
      glucotosylceramide (GluCer), lactosylceramide (LacCer) and triacylglycerol (TG)
      were down-regulated whereas glycerophosphocholine (PC) and phosphatidylinositol
      (PI) were up-regulated in the pCPA-treated mice compared with control mice.
      CONCLUSIONS: This work demonstrates the significant effects of serotonin
      deficiency on lipid metabolisms and will facilitate improved understanding of
      pathomechanisms in serotonin deficiency, particularly from a lipidomics
      perspective.

PMID- 26212165
TI  - Ghost peaks observed after atmospheric pressure matrix-assisted laser
      desorption/ionization experiments may disclose new ionization mechanism of matrix
      assisted hypersonic velocity impact ionization.
AB  - RATIONALE: Understanding the mechanisms of matrix-assisted laser
      desorption/ionization (MALDI) promises improvements in the sensitivity and
      specificity of many established applications in the field of mass spectrometry.
      This paper reports a serendipitous observation of a significant ion yield in a
      post-ionization experiment conducted after the sample had been removed from a
      standard atmospheric pressure (AP)-MALDI source. This post-ionization is
      interpreted in terms of collisions of microparticles moving with a hypersonic
      velocity into a solid surface. Calculations show that the thermal energy released
      during such collisions is close to that absorbed by the top matrix layer in
      traditional MALDI. The microparticles, containing both the matrix and analytes,
      could be detached from a film produced inside the inlet capillary during the
      sample ablation and accelerated by the flow rushing through the capillary. These
      observations contribute some new perspective to ion formation in both laser and
      laser-less matrix-assisted ionization. METHODS: An AP-MALDI ion source hyphenated
      with a three-stage high-pressure ion funnel system was utilized for peptide mass
      analysis. After the laser had been turned off and the MALDI sample removed, ions
      were detected during a gradual reduction of the background pressure in the first
      funnel. The constant-rate pressure reduction led to the reproducible appearance
      of different singly and doubly charged peptide peaks in mass spectra taken a few
      seconds after the end of the MALDI analysis of a dried-droplet spot. RESULTS: The
      ion yield as well as the mass range of ions observed with a significant delay
      after a completion of the primary MALDI analysis depended primarily on the
      background pressure inside the first funnel. The production of ions in this post
      ionization step was exclusively observed during the pressure drop. A lower matrix
      background and significant increase in relative yield of double-protonated ions
      are reported. CONCLUSIONS: The observations were partially consistent with a
      model of the supersonic jet from the inlet capillary accelerating detached
      particles to kinetic energies suitable for matrix-assisted hypersonic-velocity
      impact ionization.

PMID- 26212166
TI  - Diet-to-female and female-to-pup isotopic discrimination in South American sea
      lions.
AB  - RATIONALE: The use of accurate, species-specific diet-tissue discrimination
      factors is a critical requirement when applying stable isotope mixing models to
      predict consumer diet composition. Thus, diet-to-female and female-to-pup
      isotopic discrimination factors in several tissues for both captive and wild
      South American sea lions were estimated to provide appropriate values for
      quantifying feeding preferences at different timescales in the wild populations
      of this species. METHODS: Stable carbon and nitrogen isotope ratios in the blood
      components of two female-pup pairs and females' prey muscle from captive
      individuals were determined by elemental analyzer/isotope ratio mass spectrometry
      (EA/IRMS) to calculate the respective isotopic discrimination factors. The same
      analysis was carried out in both blood components, and skin and hair tissues for
      eight female-pup pairs from wild individuals. RESULTS: Mean diet-to-female
      Delta(13) C and Delta(15) N values were higher than the female-to-pup ones. Pup
      tissues were more (15) N-enriched than their mothers but (13) C-depleted in serum
      and plasma tissues. In most of the tissue comparisons, we found differences in
      both Delta(15) N and Delta(13) C values, supporting tissue-specific
      discrimination. We found no differences between captive and wild female-to-pup
      discrimination factors either in Delta(13) C or Delta(15) N values of blood
      components. CONCLUSIONS: Only the stable isotope ratios in pup blood are good
      proxies of the individual lactating females. Thus, we suggest that blood
      components are more appropriate to quantify the feeding habits of wild
      individuals of this species. Furthermore, because female-to-pup discrimination
      factors for blood components did not differ between captive and wild individuals,
      we suggest that results for captive experiments can be extrapolated to wild South
      American sea lion populations.

PMID- 26212167
TI  - Annotation of metabolites from gas chromatography/atmospheric pressure chemical
      ionization tandem mass spectrometry data using an in silico generated compound
      database and MetFrag.
AB  - RATIONALE: Gas chromatography (GC) coupled to atmospheric pressure chemical
      ionization quadrupole time-of-flight mass spectrometry (APCI-QTOFMS) is an
      emerging technology in metabolomics. Reference spectra for GC/APCI-MS/MS barely
      exist; therefore, in silico fragmentation approaches and structure databases are
      prerequisites for annotation. To expand the limited coverage of derivatised
      structures in structure databases, in silico derivatisation procedures are
      required. METHODS: A cheminformatics workflow has been developed for in silico
      derivatisation of compounds found in KEGG and PubChem, and validated on the Golm
      Metabolome Database (GMD). To demonstrate this workflow, these in silico
      generated databases were applied together with MetFrag to APCI-MS/MS spectra
      acquired from GC/APCI-MS/MS profiles of Arabidopsis thaliana and Solanum
      tuberosum. The Metabolite-Likeness of the original candidate structure was
      included as additional scoring term aiming at candidate structures of natural
      origin. RESULTS: The validation of our in silico derivatisation workflow on the
      GMD showed a true positive rate of 94%. MetFrag was applied to two datasets. In
      silico derivatisation of the KEGG and PubChem database served as a candidate
      source. For both datasets the Metabolite-Likeness score improved the
      identification performance. The derivatised data sources have been included into
      the MetFrag web application for the annotation of GC/APCI-MS/MS spectra.
      CONCLUSIONS: We demonstrated that MetFrag can support the identification of
      components from GC/APCI-MS/MS profiles, especially in the (common) case where
      reference spectra are not available. This workflow can be easily adapted to other
      types of derivatisation and is freely accessible together with the generated
      structure databases.

PMID- 26212168
TI  - High-performance thin-layer chromatography/desorption electrospray ionization
      mass spectrometry imaging of the crude extract from the peels of Citrus aurantium
      L. (Rutaceae).
AB  - RATIONALE: Citrus aurantium L. is a plant belonging to the Rutaceae family, whose
      extracts are extensively used in weight management products and as thermogenic
      agents. Here we present two methodologies to analyse the extracts obtained from
      the peels of Citrus aurantium L. that usually require multiple sample preparation
      and detection steps. METHODS: Polar compounds of the crude extract from the peels
      of Citrus aurantium L. (Rutaceae) were investigated by direct infusion
      electrospray ionization mass spectrometry (ESI-MS) and high-performance thin
      layer chromatography (HPTLC) coupled to desorption electrospray ionization mass
      spectrometry (DESI-MS). ESI-MS was performed in both positive and negative ion
      modes. Molecular imaging of the HPTLC plates was used for the direct analysis of
      the phytocompounds present in the crude extract from the peels of Citrus
      aurantium L. by DESI-MS imaging. RESULTS: Characteristic mass spectra with many
      diagnostic ions were obtained from the extract analysis, allowing a fast and
      reliable identification of these species. Tandem mass spectrometry (MS/MS) was
      employed to confirm the identity of specific metabolites. CONCLUSIONS: HPTLC/DESI
      MS imaging is a relatively fast, versatile, and efficient technique for natural
      product analysis, since many more ions are observed than with the direct infusion
      ESI-MS. The MS/MS technique provided information about the component structures,
      revealing the presence of important bioactive components. The application of DESI
      MS imaging may contribute to the improvement identification and characterization
      of pharmacologically active compounds in phytochemistry.

PMID- 26212169
TI  - Stable isotope signatures and trophic-step fractionation factors of fish tissues
      collected as non-lethal surrogates of dorsal muscle.
AB  - RATIONALE: Dorsal white muscle is the standard tissue analysed in fish trophic
      studies using stable isotope analyses. As muscle is usually collected
      destructively, fin tissues and scales are often used as non-lethal surrogates; we
      examined the utility of scales and fin tissue as muscle surrogates. METHODS: The
      muscle, fin and scale delta(15) N and delta(13) C values from 10 cyprinid fish
      species determined with an elemental analyser coupled with an isotope ratio mass
      spectrometer were compared. The fish comprised (1) samples from the wild, and (2)
      samples from tank aquaria, using six species held for 120 days and fed a single
      food resource. Relationships between muscle, fin and scale isotope ratios were
      examined for each species and for the entire dataset, with the efficacy of four
      methods of predicting muscle isotope ratios from fin and scale values being
      tested. The fractionation factors between the three tissues of the laboratory
      fishes and their food resource were then calculated and applied to Bayesian
      mixing models to assess their effect on fish diet predictions. RESULTS: The
      isotopic data of the three tissues per species were distinct, but were
      significantly related, enabling estimations of muscle values from the two
      surrogates. Species-specific equations provided the least erroneous corrections
      of scale and fin isotope ratios (errors < 0.60/00). The fractionation factors for
      delta(15) N values were in the range obtained for other species, but were often
      higher for delta(13) C values. Their application to data from two fish
      populations in the mixing models resulted in significant alterations in diet
      predictions. CONCLUSIONS: Scales and fin tissue are strong surrogates of dorsal
      muscle in food web studies as they can provide estimates of muscle values within
      an acceptable level of error when species-specific methods are used. Their
      derived fractionation factors can also be applied to models predicting fish diet
      composition from delta(15) N and delta(13) C values.

PMID- 26212170
TI  - Vitamin D supplementation reduces depressive symptoms in patients with chronic
      liver disease.
AB  - BACKGROUND AND AIMS: Vitamin D deficiency and depression frequently occur in
      patients with chronic liver diseases (CLD). Depression has recently been
      inversely associated with vitamin D in a meta-analysis, and vitamin D receptor is
      expressed in brain. This pilot study investigates whether vitamin D replacement
      ameliorates depressive symptoms in CLD patients and consists of a cross-sectional
      and an interventional analysis. METHODS: Overall, 111 patients with CLD were
      included in the cross-sectional analysis. The Beck Depression Inventory II (BDI
      II) was used to assess depression. Chemiluminescence immunoassay and LC-MS/MS
      quantified serum 25-hydroxyvitamin D levels. For the interventional analysis, 77
      patients with inadequate vitamin D concentrations received 20,000 IU vitamin D
      per week for six months. The final follow-up was carried out six months post
      supplementation. RESULTS: In the cross-sectional analysis, 81% of patients
      (median age 55 years, 47% women) had inadequate baseline vitamin D levels (<30
      ng/ml), and 31% presented with depressive symptoms (BDI-II score >=14).
      Depression severity correlated inversely with vitamin D level in depressed
      patients (beta = -0.483, P = 0.004). Depression scores improved significantly
      from baseline in depressed patients after three and six months (P = 0.003 and P =
      0.004, respectively) of supplementation, with vitamin D levels increasing to
      normal (P < 0.0001). Subgroup analyses revealed this anti-depressant effect of
      vitamin D to occur predominantly in women. The final follow-up showed increases
      in median BDI-II scores in the setting of decreased vitamin D levels.
      CONCLUSIONS: Vitamin D levels correlated with BDI-II scores, and vitamin D
      replacement significantly improved depressive symptoms in women with CLD.
      Adjuvant vitamin D may be considered in these patients. REGISTRATION NO:
      DRKS00007782 German Clinical Trials Registry (DRKS).

PMID- 26212171
TI  - Combining nutrition and exercise to optimize survival and recovery from critical
      illness: Conceptual and methodological issues.
AB  - Survivors of critical illness commonly experience neuromuscular abnormalities,
      including muscle weakness known as ICU-acquired weakness (ICU-AW). ICU-AW is
      associated with delayed weaning from mechanical ventilation, extended ICU and
      hospital stays, more healthcare-related hospital costs, a higher risk of death,
      and impaired physical functioning and quality of life in the months after ICU
      admission. These observations speak to the importance of developing new
      strategies to aid in the physical recovery of acute respiratory failure patients.
      We posit that to maintain optimal muscle mass, strength and physical function,
      the combination of nutrition and exercise may have the greatest impact on
      physical recovery of survivors of critical illness. Randomized trials testing
      this and related hypotheses are needed. We discussed key methodological issues
      and proposed a common evaluation framework to stimulate work in this area and
      standardize our approach to outcome assessments across future studies.

PMID- 26212172
TI  - Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on
      maximum heart rate after exercise testing in chronic fatigue syndrome - A
      randomized, controlled, double-blind trial.
AB  - BACKGROUND & AIMS: Chronic Fatigue Syndrome (CFS) is a complex condition,
      characterized by severe disabling fatigue with no known cause, no established
      diagnostic tests, and no universally effective treatment. Several studies have
      proposed symptomatic treatment with coenzyme Q10 (CoQ10) and nicotinamide adenine
      dinucleotide (NADH) supplementation. The primary endpoint was to assess the
      effect of CoQ10 plus NADH supplementation on age-predicted maximum heart rate
      (max HR) during a cycle ergometer test. Secondary measures included fatigue, pain
      and sleep. METHODS: A proof-of-concept, 8-week, randomized, controlled, double
      blind trial was conducted in 80 CFS patients assigned to receive either CoQ10
      plus NADH supplementation or matching placebo twice daily. Maximum HR was
      evaluated at baseline and at end of the run-in period using an exercise test.
      Fatigue, pain and sleep were evaluated at baseline, and then reassessed at 4- and
      8-weeks through self-reported questionnaires. RESULTS: The CoQ10 plus NADH group
      showed a significant reduction in max HR during a cycle ergometer test at week 8
      versus baseline (P = 0.022). Perception of fatigue also showed a decrease through
      all follow-up visits in active group versus placebo (P = 0.03). However, pain and
      sleep did not improve in the active group. Coenzyme Q10 plus NADH was generally
      safe and well tolerated. CONCLUSIONS: Our results suggest that CoQ10 plus NADH
      supplementation for 8 weeks is safe and potentially effective in reducing max HR
      during a cycle ergometer test and also on fatigue in CFS. Further additional
      larger controlled trials are needed to confirm these findings. Clinical trial
      registrationThis trial was registered at clinicaltrials.gov as NCT02063126.

PMID- 26212173
TI  - Proteomic analysis reveals that COP9 signalosome complex subunit 7A (CSN7A) is
      essential for the phase transition of migratory locust.
AB  - The migratory locust displays a reversible, density-dependent transition between
      the two phases of gregaria and solitaria. This phenomenon is a typical kind of
      behavior plasticity. Here, we report that COP9 signalosome complex subunit 7A
      (CSN7A) is involved in the regulation of locust phase transition. Firstly, 90
      proteins were identified to express differentially between the two phases by
      quantitative proteomic analysis. Gregaria revealed higher levels in proteins
      related to structure formation, melanism and energy metabolism, whereas solitaria
      had more abundant proteins related to digestion, absorption and chemical sensing.
      Subsequently, ten proteins including CSN7A were found to reveal differential mRNA
      expression profiles between the two phases. The CSN7A had higher mRNA level in
      the gregaria as compared with the solitaria, and the mRNA amount in the gregaria
      decreased remarkably during the 32 h-isolation. However, the mRNA level in the
      solitaria kept constant during the crowding rearing. Finally and importantly, RNA
      interference of CSN7A in gregaria resulted in obvious phase transition towards
      solitaria within 24 h. It suggests that CSN7A plays an essential role in the
      transition of gregaria towards solitaria in the migratory locust. To our
      knowledge, it's the first time to report the role of CSN in behavior plasticity
      of animals. 

PMID- 26212174
TI  - A significant and consistent reduction in rotavirus gastroenteritis
      hospitalization of children under 5 years of age, following the introduction of
      universal rotavirus immunization in Israel.
AB  - Universal rotavirus vaccination with RotaTeq was introduced in Israel in December
      2010. We examined hospitalization rates of children under 5 years of age due to
      all-cause and rotavirus gastroenteritis, both before and 3 years after universal
      introduction of the vaccination. An ongoing hospital-based surveillance network
      that was established in November 2007, accessed information regarding
      hospitalization of children due to gastroenteritis (n = 6205) in 3 hospitals in
      northern Israel, with an annual average of about 60,000 children under 5 years of
      age living in the catchment area of these hospitals. Stool samples were tested
      for rotavirus by immunochromatography. Compared to the period preceding
      implementation of the universal rotavirus vaccination (2008-2010),
      hospitalizations due to rotavirus gastroenteritis in children <5 years of age
      decreased significantly, by 55% (95% CI 43%-67%) during the period of universal
      vaccination (2011-2013), a decrease that was sustained throughout the 3 year
      period. This reduction was greater in children aged 0-23 months (60-61%) than in
      toddlers aged 24-59 months (36%). A 32% (95% CI 21%-45%) decrease in the
      incidence of all-cause gastroenteritis was also observed. During the period
      preceding universal vaccination, rotavirus diarrhea showed typical winter
      seasonality, with highest incidence in December. However, the winter peak was
      substantially blunted during the period of universal immunization. Surveillance
      of rotavirus gastroenteritis should continue to assess the long-term impact of
      such a program. Our findings are of relevance to high and middle-income countries
      considering the introduction of a universal rotavirus immunization program.

PMID- 26212175
TI  - Association of interleukin4 gene polymorphisms of recipients and donors with
      acute rejection following living donor liver transplantation.
AB  - BACKGROUND: Little is known as to whether the interleukin4 (IL4) gene
      polymorphisms in recipients or donors affect the incidence of acute cellular
      rejection (ACR) following living donor liver transplantation (LDLT). Therefore,
      we determined the effect of IL4 T-33C polymorphisms in recipients and donors on
      ACR in a large cohort of patients that underwent LDLT. METHODS: We examined 155
      LDLT cases treated at Nagoya University or Kyoto University, Japan, between 2004
      and 2009. IL4 T-33C polymorphisms were analyzed in recipients and donors.
      RESULTS: Forty-seven recipients (30.3%) developed early ACR. The genotype
      frequency of IL4 T-33C in the recipients was associated with ACR incidence
      (P=0.008, P<0.0125 considered significant). Patients with the IL4-33C carrier
      genotype (C/C or C/T) were significantly associated with a higher incidence of
      ACR relative to those with the T/T genotype (OR=3.27, 95% CI: 1.56-6.88,
      P=0.002). The genotype frequencies of IL4 T-33C in the donors were not associated
      with rejection incidence. In addition, there was no significant effect of IL4 T
      33C genotype combinations on ACR incidence in donors and recipients. CONCLUSIONS:
      Genotyping of IL4 T-33C in recipients might be useful to stratify the liver
      transplant recipients according to their risk of ACR.

PMID- 26212176
TI  - Versatility of stem and progenitor cells and the instructive actions of cytokines
      on hematopoiesis.
AB  - For many years, developing hematopoietic cells have been strictly
      compartmentalized into a rare population of multi-potent self-renewing
      hematopoietic stem cells (HSC), multi-potent hematopoietic progenitor cells (MPP)
      that are undergoing commitment to particular lineage fates, and recognizable
      precursor cells that mature towards functional blood and immune cells. A single
      route to each end-cell type is prescribed in the "classical" model for the
      architecture of hematopoiesis. Recent findings have led to the viewpoint that
      HSCs and MPPs are more versatile than previously thought. Underlying this are
      multiple routes to a particular fate and cells having clandestine fate options
      even when they have progressed some way along a pathway. The primary role of
      cytokines during hematopoiesis has long been seen to be regulation of the
      survival and proliferation of developing hematopoietic cells. Some cytokines now
      clearly have instructive actions on cell-fate decisions. All this leads to a new
      way of viewing hematopoiesis whereby versatile HSC and MPP are directed towards
      lineage outcomes via cytokine regulated cell-fate decisions. This means greater
      flexibility to the shaping of hematopoiesis. 

PMID- 26212177
TI  - Electrochemical stability of Sm(0.5)Sr(0.5)CoO(3-delta)-infiltrated YSZ for solid
      oxide fuel cells/electrolysis cells.
AB  - Composite SSC (Sm(0.5)Sr(0.5)CoO(3-delta))-YSZ (yttria stabilized zirconia)
      oxygen electrodes were prepared by an infiltration process. X-ray diffraction
      (XRD) analysis and scanning electron microscopy (SEM) of the composite electrodes
      showed the formation of SSC perovskite and a well-connected network of SSC
      particles in the porous YSZ backbone, respectively. The electrochemical
      performance of the cell was investigated under both fuel cell and steam
      electrolysis modes using polarization curves and electrochemical impedance
      spectroscopy (EIS). The cell experienced a large degradation rate at 700  degrees
      C with a constant voltage of 0.7 V for over 100 h under power generation
      operation. The subsequent post-cell SEM micrograph revealed that agglomeration of
      the infiltrated SSC particles was possibly the cause for the performance
      deterioration. Furthermore, the long-term stability of the cell was examined at
      700  degrees C with a constant voltage of 1.3 V under steam electrolysis mode.
      SEM associated with energy dispersive X-ray spectroscopy (EDS) was employed to
      characterize the post-test cell after the long-term electrolysis operation and it
      indicated that besides the agglomeration of SSC particles, the delamination of
      the SSC-YSZ oxygen electrode from the YSZ electrolyte, as well as segregation of
      cobalt-enriched particles (particularly cobalt oxides) at the interface, was
      probably responsible for the cell degradation under the steam electrolysis mode.

PMID- 26212178
TI  - Changing paradigms in the systemic treatment of advanced cervical cancer.
AB  - Despite availability of primary and secondary prevention measures, cervical
      cancer persists as one of the most common cancers among women around the world.
      Although early-stage disease can be cured with radical and even fertility-sparing
      surgery, patients with metastatic and recurrent cervical cancer have poor
      prognosis with historically limited treatment options and incurable disease.
      Significant advances in cervical cancer treatment have emerged as the result of
      clinical trials that have sought to determine the best therapy to prolong overall
      and progression-free survival. Most recently, trials that have involved
      angiogenesis blockade in addition to standard chemotherapy have demonstrated
      improved overall and progression-free survival. This review serves to highlight
      pivotal trials in chemotherapy development for advanced, metastatic, and
      recurrent cervical cancer that includes the paradigm-shifting work that
      demonstrates increased overall survival with angiogenesis blockade. 

PMID- 26212179
TI  - Ethical issues identified by obstetrics and gynecology learners through a novel
      ethics curriculum.
AB  - OBJECTIVE: Obstetrics and gynecology (ob/gyn) is fraught with bioethical issues,
      the professional significance of which may vary based on clinical experience. Our
      objective was to utilize our novel ethics curriculum to identify ethics and
      professionalism issues highlighted by ob/gyn learners and to compare responses
      between learner levels to further inform curricular development. STUDY DESIGN: We
      introduced an integrated and dynamic ob/gyn ethics and professionalism curriculum
      and mixed methods analysis of 181 resulting written reflections (case observation
      and assessments) from third-year medical students and from first- to fourth-year
      ob/gyn residents. Content was compared by learner level using basic thematic
      analysis and summary statistics. RESULTS: Within the 7 major ethics and
      professionalism domains, learners wrote most frequently about miscellaneous
      ob/gyn issues such as periviability and abortion (22% of students, 20% of
      residents) and problematic treatment decisions (20% of students, 19% of
      residents) rather than professional duty, communication, justice, student
      /resident-specific issues, or quality of care. The most commonly discussed ob/gyn
      area by both learner groups was obstetrics rather than gynecology, gynecologic
      oncology, or reproductive endocrinology and infertility, although residents were
      more likely to discuss obstetrics-related concerns than students (65% vs 48%; P =
      .04) and students wrote about gynecologic oncology-related concerns more
      frequently than residents (25% vs 6%; P = .002). In their reflections, sources of
      ethical value (eg, the 4 classic ethics principles, professional guidelines, and
      consequentialism) were cited more frequently and in greater number by students
      than by residents (82% of students cited at least 1 source of ethical value vs
      65% of residents; P = .01). Residents disagreed more frequently with the ethical
      propriety of clinical management than did students (67% vs 43%; P = .005).
      CONCLUSION: Our study introduces an innovative and dynamic approach to an ob/gyn
      ethics and professionalism curriculum that highlights important learner
      identified ethics and professionalism issues both specific to ob/gyn and common
      to clinical medicine. Findings will help ob/gyn educators best utilize and refine
      this flexible curriculum such that it is appropriately focused on topics relevant
      to each learner level.

PMID- 26212180
TI  - Challenging the 4- to 5-minute rule: from perimortem cesarean to resuscitative
      hysterotomy.
AB  - Although perimortem delivery has been recorded in the medical literature for
      millennia, the procedural intent has evolved to the current fetocentric approach,
      predicating timing of delivery following maternal cardiopulmonary arrest to
      optimize neonatal outcome. We suggest a call to action to reinforce the concept
      that if the uterus is palpable at or above the umbilicus, preparations for
      delivery should be made simultaneous with initiation of maternal resuscitative
      efforts; if maternal condition is not rapidly reversible, hysterotomy with
      delivery should be performed regardless of fetal viability or elapsed time since
      arrest. Cognizant of the difficulty in determining precise timing of arrest in
      clinical practice, if fetal status is already compromised further delay while
      attempting to assess fetal heart rate, locating optimal surgical equipment, or
      transporting to an operating room will result in unnecessary worsening of both
      maternal and fetal condition. Even if intrauterine demise has already occurred,
      maternal resuscitative efforts will typically be markedly improved following
      delivery with uterine decompression. Consequently we suggest that perimortem
      cesarean delivery be renamed "resuscitative hysterotomy" to reflect the mutual
      optimization of resuscitation efforts that would potentially provide earlier and
      more substantial benefit to both mother and baby. 

PMID- 26212181
TI  - Role of catecholamines in maternal-fetal stress transfer in sheep.
AB  - OBJECTIVE: We sought to evaluate whether in addition to cortisol, catecholamines
      also transfer psychosocial stress indirectly to the fetus by decreasing uterine
      blood flow (UBF) and increasing fetal anaerobic metabolism and stress hormones.
      STUDY DESIGN: Seven pregnant sheep chronically instrumented with uterine
      ultrasound flow probes and catheters at 0.77 gestation underwent 2 hours of
      psychosocial stress by isolation. We used adrenergic blockade with labetalol to
      examine whether decreased UBF is catecholamine mediated and to determine to what
      extent stress transfer from mother to fetus is catecholamine dependent. RESULTS:
      Stress induced transient increases in maternal cortisol and norepinephrine (NE).
      Maximum fetal plasma cortisol concentrations were 8.1 +/- 2.1% of those in the
      mother suggesting its maternal origin. In parallel to the maternal NE increase,
      UBF decreased by maximum 22% for 30 minutes (P < .05). Fetal NE remained elevated
      for >2 hours accompanied by a prolonged blood pressure increase (P < .05).
      Fetuses developed a delayed and prolonged shift toward anaerobic metabolism in
      the presence of an unaltered oxygen supply. Adrenergic blockade prevented the
      stress-induced UBF decrease and, consequently, the fetal NE and blood pressure
      increase and the shift toward anaerobic metabolism. CONCLUSION: We conclude that
      catecholamine-induced decrease of UBF is a mechanism of maternal-fetal stress
      transfer. It may explain the influence of maternal stress on fetal development
      and on programming of adverse health outcomes in later life especially during
      early pregnancy when fetal glucocorticoid receptor expression is limited.

PMID- 26212182
TI  - Menstrual preconditioning for the prevention of major obstetrical syndromes in
      polycystic ovary syndrome.
AB  - The presence of multiple ovarian cysts, anovulation, and endometrial progesterone
      resistance in the neonate seems remarkably similar to ovarian and endometrial
      features of the polycystic ovary syndrome (PCOS) of adolescent and adult women.
      In fact, in the absence of cyclic menstruations after menarche, the neonatal
      progesterone resistance is likely to persist and adversely affect young women
      with PCOS at the time of pregnancy after induction of ovulation, because any
      persisting defect in progesterone response can interfere with the process of
      decidualization and trophoblast invasion. The primigravid woman with PCOS
      therefore is likely to be at risk of defective deep placentation as manifested by
      the increased risk of major obstetric syndromes. A recent, large epidemiologic
      study has demonstrated that the risk of preeclampsia and preterm delivery is
      elevated in the 13- to 15-year old group, although it does not persist in the 16-
      to 17-year old group. It is proposed therefore that induction of ovulation in the
      infertile nulligravid woman with PCOS should be preceded by a period of
      progesterone withdrawal bleedings to achieve full endometrial progesterone
      response by the time of pregnancy. The cyclic administration of clomiphene
      citrate for a period to be determined by vascular response may be an appropriate
      tool to reduce the risk of major obstetric syndromes by menstrual
      preconditioning. 

PMID- 26212183
TI  - Treatment of colour industry wastewaters with concomitant bioelectricity
      production in a sequential stacked mono-chamber microbial fuel cells-aerobic
      system.
AB  - The scalability of any microbial fuel cell (MFC)-based system is of vital
      importance if it is to be utilized for potential field applications. In this
      study, an integrated MFC-aerobic bioreactor system was investigated for its
      scalability with the purpose of treating a simulated dye wastewater and
      industrial wastewaters originated from textile dyebaths and leather tanning. The
      influent containing real wastewater was fed into the reactor in continuous mode
      at ambient temperature. Three MFC units were integrated to act in unison as a
      single module for wastewater treatment and a continuously stirred aerobic
      bioreactor operating downstream to the MFC module was installed in order to
      ensure more complete degradation of colouring agents found in the wastewater.
      Total colour removal in the final effluent exceeded 90% in all experiments where
      both synthetic (AO-7 containing) and real wastewater were used as the influent
      feed. The chemical oxygen demand reduction also exceeded 80% in all experiments
      under the same conditions. The MFC modules connected in parallel configuration
      allowed obtaining higher current densities than that can be obtained from a
      single MFC unit. The maximum current density of the MFC stack reached 1150 mA m(
      2) when connected in a parallel configuration. The outcome of this work implies
      that suitably up-scaled MFC-aerobic integrated bioprocesses could be used for
      colour industry wastewater treatment under industrially relevant conditions with
      possible prospects of bioelectricity generation.

PMID- 26212184
TI  - Endogenous methicillin-resistant Staphylococcus aureus endophthalmitis after leg
      trauma.
AB  - We present a case of endogenous endophthalmitis in a 13-year-old boy with
      methicillin-resistant Staphylococcus aureus sepsis. The patient underwent
      magnetic resonance imaging of the brain after intermittent anisocoria was noted
      on examination, leading to a diagnosis of endophthalmitis with a chorodial
      abscess. 

PMID- 26212185
TI  - Isolated ocular lichen planus in a child.
AB  - Lichen planus (LP) is an autoimmune inflammatory condition of the skin and mucous
      membranes, of unknown aetiology, that infrequently involves the eye. Ocular LP
      has not been described in children. We present the case of an 8-year-old girl
      with severe, filamentous dry eyes and persistent conjunctival hyperemia with
      bilateral progressive conjunctival symblepharon. Her conjunctival biopsy showed
      heavy linear fibrinogen deposits along the basement membrane without IgG, IgA,
      IgM, or C3 deposition, consistent with LP. No skin or other mucosal lesions were
      present, suggesting a diagnosis of isolated conjunctival LP. Oral and topical
      cyclosporine combined with methotrexate and low-dose oral steroids led to
      sustained disease remission. To our knowledge, this is the first case of isolated
      ocular LP in a child. 

PMID- 26212187
TI  - Small GSH-Capped CuInS2 Quantum Dots: MPA-Assisted Aqueous Phase Transfer and
      Bioimaging Applications.
AB  - An efficient ligand exchange strategy for aqueous phase transfer of hydrophobic
      CuInS2/ZnS quantum dots was developed by employing glutathione (GSH) and
      mercaptopropionic acid (MPA) as the ligands. The whole process takes less than 20
      min and can be scaled up to gram amount. The material characterizations show that
      the final aqueous soluble samples are solely capped with GSH on the surface.
      Importantly, these GSH-capped CuInS2/ZnS quantum dots have small size
      (hydrodynamic diameter <10 nm), moderate fluorescent properties (up to 34%) as
      well as high stability in aqueous solutions (stable for more than three months in
      4  degrees C without any significant fluorescence quenching). Moreover, this
      ligand exchange strategy is also versatile for the aqueous phase transfer of
      other hydrophobic quantum dots, for instance, CuInSe2 and CdSe/ZnS quantum dots.
      We further demonstrated that GSH-capped quantum dots could be suitable
      fluorescence markers to penetrate cell membrane and image the cells. In addition,
      the GSH-capped CuInS2 quantum dots also have potential use in other fields such
      as photocatalysis and quantum dots sensitized solar cells. 

PMID- 26212186
TI  - Three-dimensional visualization of the microvasculature of bile duct ligation
      induced liver fibrosis in rats by x-ray phase-contrast imaging computed
      tomography.
AB  - X-ray phase-contrast imaging (PCI) can substantially enhance contrast, and is
      particularly useful in differentiating biological soft tissues with small density
      differences. Combined with computed tomography (CT), PCI-CT enables the
      acquisition of accurate microstructures inside biological samples. In this study,
      liver microvasculature was visualized without contrast agents in vitro with PCI
      CT using liver fibrosis samples induced by bile duct ligation (BDL) in rats. The
      histological section examination confirmed the correspondence of CT images with
      the microvascular morphology of the samples. By means of the PCI-CT and three
      dimensional (3D) visualization technique, 3D microvascular structures in samples
      from different stages of liver fibrosis were clearly revealed. Different types of
      blood vessels, including portal veins and hepatic veins, in addition to ductular
      proliferation and bile ducts, could be distinguished with good sensitivity,
      excellent specificity and excellent accuracy. The study showed that PCI-CT could
      assess the morphological changes in liver microvasculature that result from
      fibrosis and allow characterization of the anatomical and pathological features
      of the microvasculature. With further development of PCI-CT technique, it may
      become a novel noninvasive imaging technique for the auxiliary analysis of liver
      fibrosis. 

PMID- 26212188
TI  - Child maltreatment and military-connected youth: Developing protective school
      communities: School responses of referral and clinical interventions do not
      address needs of military families.

PMID- 26212189
TI  - The Contribution to Suicide Prevention of Restricting Access to Methods and
      Sites.

PMID- 26212190
TI  - Prevention of Deaths from Intentional Pesticide Poisoning.
AB  - Ingestion of pesticides is the most common suicide method worldwide, accounting
      for one third of all suicides, predominantly in Asia, Africa, Central and South
      America. Case fatalities are high, particularly in rural areas. This high case
      fatality may explain the similar numbers of male and female suicides in Asia,
      since more women die from their attempts. In Asia, pesticide suicides are mostly
      impulsive acts with little advance planning and they are less often associated
      with mental illness than in Western countries. Pesticides are generally chosen
      for their easy access. Prevention strategies include treating the problems
      leading to suicidal behaviors involving pesticides; changing attitudes,
      knowledge, and beliefs about pesticides; controlling access to dangerous
      pesticides, including developing secure storage practices (which are currently
      being evaluated); and improving the medical treatment of poisonings. More
      research is needed to better understand suicides involving pesticides in their
      cultural contexts and to evaluate the effectiveness of intervention programs,
      including assessment of possible substitution of methods. Also, more knowledge
      about protective factors may help suggest innovative prevention strategies. 

PMID- 26212191
TI  - Charcoal-Burning Suicides and Strategies for Prevention.
AB  - This paper examines the emergence of a new method of suicide in Hong Kong by
      carbon monoxide poisoning generated by the burning of charcoal. In just 6 years,
      it has become the second most common means of suicide after jumping from heights.
      The profile of these charcoal-burning suicide victims is different from that of
      other suicide deaths. It seems that a significant proportion of the increase in
      the number of suicides for the period is attributable to the charcoal burning.
      The effect of mass media reporting and strategies on how to contain the
      contagious effect of charcoal-burning deaths are discussed. 

PMID- 26212192
TI  - Motor Vehicle Exhaust Gas Suicide.
AB  - In many motorized countries, inhalation of carbon monoxide from motor vehicle
      exhaust gas (MVEG) has been one of the leading methods of suicide. In some
      countries it remains so (e.g., Australia 16.0% of suicides in 2005). Relative to
      other methods it is a planned method and one often used by middle-aged males. The
      study provides a review of countermeasures aimed at restricting this method of
      suicide. The prevention measures identified were catalytic converters (introduced
      to reduce carbon monoxide for environmental reasons); in-cabin sensors; exhaust
      pipe modification; automatic idling stops; and helpline signage at suicide
      "hotspots." Catalytic converters are now in 90% of new vehicles worldwide and
      literature supports them being associated with a reduction in exhaust-gassing
      suicides. There remain, however, accounts of exhaust-gas fatalities in modern
      vehicles, whether accidentally or by suicide. These deaths and also crashes from
      fatigue could potentially be prevented by in-cabin multi-gas sensors, these
      having been developed to the prototype stage. Helpline signage at an exhaust
      gassing suicide "hotspot" had some success in reducing suicides. The evidence on
      method substitution and whether a reduction in MVEG suicides causes a reduction
      in total suicides is inconsistent. 

PMID- 26212193
TI  - Railway and Metro Suicides.
AB  - This article reviews research on railway and metro (underground and subway)
      suicides around the world. Although the incidence and survival rates vary and
      standardized methodologies are lacking, it is evident that there is a high
      incidence among psychiatric patients and at stations, crossings, and track areas
      near psychiatric institutions. Fictional and news reports of railway and metro
      suicides are related to increased rates, and false beliefs about a certain,
      fatal, and painless outcome may contribute to use of this method. Train drivers
      and rail personnel are often traumatized and in need of personal support after
      the incident. Most prevention involves surveillance, limiting access to tracks,
      or prompt intervention during an attempt. Other potential strategies include
      focusing upon the high-risk populations of previous attempters and patients in
      psychiatric facilities near stations and tracks and changing attitudes concerning
      the acceptability of this method to ensure that potentially suicidally active
      individuals are not under the illusion that this is a certain and painless method
      of death. 

PMID- 26212194
TI  - Restrictions in Availability of Drugs Used for Suicide.
AB  - Availability of drugs with high lethality has been hypothesized to increase the
      risk of self-poisoning suicides. A literature search concerning deliberate self
      poisoning and the effect of restricting access to drugs was conducted, and the
      effect of restrictions in availability of barbiturates, tricyclic
      antidepressants, dextropropoxyphene, and weak analgesics was reviewed. The
      correlations between method-specific and overall suicide rates and sales figures
      for barbiturates, dextropropoxyphene, weak analgesics, and tricyclic
      antidepressants were reviewed. It is concluded that restriction in availability
      of drugs with high case fatality should be a part of suicide prevention
      strategies. 

PMID- 26212195
TI  - Gun-Control Legislation and the Impact on Suicide.
AB  - Gun control is the prototypical example of controlling the environment for the
      means of suicide, an effective public health approach to suicide prevention.
      Canada's Criminal Law Amendment Act of 1977 (Bill C-51) provides an excellent
      opportunity to illustrate the effects of legislative gun-control laws and the
      impact on suicide. The research in Canada supports the significant effect of C-51
      in reducing suicides and firearm suicides, even if one controls for socioeconomic
      factors, although not equally for all ages. The young, a high-risk group, show
      the most significant decrease, without significant substitution of other methods
      (displacement). Studies on gun-control laws from New Zealand, the United States,
      and Australia support the Canadian findings. It is concluded that, although not
      equally applicable in all countries, gun control may well have significant
      applications in reducing suicide worldwide. 

PMID- 26212196
TI  - Suicide by Jumping.
AB  - Research on suicide by jumping is summarized. The incidence of suicide by this
      method varies but tends to be higher in cities, city states, or countries that
      have extensive high-rise housing. Most suicides by jumping occur from high-rise
      residential housing units. However, our knowledge about suicide by jumping tends
      to be limited to a small number of reports from sites, often bridges, which
      become well-known as places from which to take one's life. Media reports of
      newsworthy suicides from these sites appear to encourage imitative behavior.
      Prevention strategies have focused upon limiting suicides from iconic sites by
      surveillance, barriers, muted media reporting, and signage offering help and
      telephone hotlines. A small number of studies provides evidence that installing
      barriers at popular jumping sites reduces suicides from those sites. There are
      few reports of efforts to reduce suicides from high-rise residential buildings. 

PMID- 26212197
TI  - Media Reporting of Suicide Methods.
AB  - Internationally, media guidelines on the reporting of suicide suggest that the
      method of suicide should not be explicitly reported. This paper presents
      quantitative data on the reporting of suicide in Australia, which suggest that
      the media present a skewed image of reality with an over-reporting of suicide by
      violent and unusual methods. It also presents qualitative textual analyses of
      examples of newspaper reports of suicide in an attempt to examine differences in
      reporting practices across media and genres and to explore the limits of the
      notion of "explicitness." The paper concludes that journalistic decisions to
      maximize the newsworthiness of a story often conflict with the promotion of the
      accurate, ethical, and responsible reporting of suicide. 

PMID- 26212198
TI  - Adherence to the gluten-free diet can achieve the therapeutic goals in almost all
      patients with coeliac disease: A 5-year longitudinal study from diagnosis.
AB  - BACKGROUND: Key aims of treatment of coeliac disease are to heal the intestinal
      mucosa and correct nutritional abnormalities. AIM: We aim to determine
      prospectively the degree of success and time course of achieving those goals with
      a gluten-free diet. METHODS: Ninety-nine patients were enrolled at diagnosis and
      taught the diet. The first 52 were reassessed at 1 year and 46 at 5 years, 25
      being assessed at the three time points regarding dietary compliance (dietitian
      assessed), coeliac serology, bone mineral density and body composition analysis
      by dual energy X-ray absorptiometry, and intestinal histology. RESULTS: Mean age
      (range) was 40 (18-71) years and 48 (76%) were female. Dietary compliance was
      very good to excellent in all but one. Tissue transglutaminase IgA was
      persistently elevated in 44% at 1 year and 30% at 5 years and were poorly
      predictive of mucosal disease. Rates of mucosal remission (Marsh 0) and response
      (Marsh 0/1) were 37% and 54%, and 50% and 85% at 1 and 5 years, respectively. Fat
      mass increased significantly over the first year in those with normal/reduced
      body mass index. Lean body mass indices more slowly improved irrespective of
      status at diagnosis with significant improvement at 5 years. Bone mass increased
      only in those with osteopenia or osteoporosis, mostly in year 1. CONCLUSION:
      Dietary compliance is associated with a high chance of healing the intestinal
      lesion and correction of specific body compositional abnormalities. The time
      course differed with body fat improving within 1 year, and correction of the
      mucosal lesion and improvement in lean mass and bone mass taking longer.

PMID- 26212199
TI  - BET Inhibition Upregulates SIRT1 and Alleviates Inflammatory Responses.
AB  - Control of histone acetylation is a part of the epigenetic mechanism that
      regulates gene expression and chromatin architecture. The members of the
      bromodomain and extra terminal domain (BET) protein family are a group of
      epigenetic readers that recognize histone acetylation, whereas histone deacetyl-
      ases such as sirtuin 1 (SIRT1) function as epigenetic erasers. We observed that
      BET inhibition by the specific inhibitor JQ1 upregulated SIRT1 expression and
      activated SIRT1. Moreover, we observed that BET inhibition functionally reversed
      the pro-inflammatory effect of SIRT1 inhibition in a cellular lung disease model.
      SIRT1 activation is desirable in many age-related, metabolic and inflammatory
      diseases; our results suggest that BET protein inhibition would be beneficial in
      treatment of those conditions. Most importantly, our findings demonstrate a novel
      mechanism of SIRT1 activation by inhibition of the BET proteins. 

PMID- 26212200
TI  - [Assessment of 10 years of memory consultations in the Franche-Comte: Description
      and analysis of the RAPID regional database].
AB  - The aim of this study was to evaluate the impact, on a regional scale (Franche
      Comte), of 3 National Alzheimer care plans, particularly concerning the
      development of the offer of care management by clinicians as well as the panel of
      diagnoses concerned. Data on sociodemographic, neuropsychological and diagnostic
      characteristics were retrieved from the RAPID regional database between 1st
      January 2003 and 31st December 2012. These analyses focused exclusively on
      patients who had an initial consultation (n=12,017) during the same period. The
      existence of a previously established health network capable of carrying out
      governmental health plans has produced an effective interface between regional
      administrative structures responsible for the implementation of these plans and
      health professionals responsible for carrying out them out. This network study,
      the use of a battery of tests and a common software database have enabled the
      development of patient care management throughout the Franche-Comte region. It
      also showed the diversification of diagnoses mentioned over the past years as
      well as changes in clinical practices on how to address the issue of cognitive
      impairment. 

PMID- 26212201
TI  - Resveratrol inhibits TIGAR to promote ROS induced apoptosis and autophagy.
AB  - Resveratrol has been shown to exhibit its anti-cancer effect through a variety of
      mechanisms. Here, TIGAR (TP53-Induced Glycolysis and Apoptosis Regulator) was
      identified as an important target of resveratrol for exhibiting ROS-dependent
      consequences on apoptosis and autophagy. Resveratrol treatment decreased TIGAR
      protein irrespective of cell line used. Down-regulated TIGAR protein triggered a
      drop in reduced-glutathione levels which resulted in sustained ROS, responsible
      for apoptosis and autophagy. Over-expression and silencing experiments
      demonstrated the importance of TIGAR in affecting the ROS-dependent anti-cancer
      effects of resveratrol. Resveratrol treated cells exhibited autophagy to escape
      apoptosis, however, chloroquine treatment along with resveratrol, blocked
      protective autophagy and facilitated apoptosis. Collectively, results unravel the
      effects of resveratrol on TIGAR in mediating its ROS dependent influence and
      suggest a better combination therapy of resveratrol and chloroquine for probable
      cancer treatment. 

PMID- 26212202
TI  - Eye movements reveal mechanisms underlying attentional biases towards threat.
AB  - Mechanisms underlying attentional biases towards threat (ABTs), such as
      attentional avoidance and difficulty of disengagement, are still unclear. To
      address this issue, we recorded participants' eye movements during a dot
      detection task in which threatening or neutral stimuli served as peripheral cues.
      We evaluated response times (RTs) in trials where participants looked at the
      central fixation cross (not at the cues), as they were required, and number and
      duration of (unwanted) fixations towards threatening or neutral cues; in all
      analyses trait anxiety was treated as a covariate. Difficulty in attentional
      disengagement (longer RTs) was found when peripheral threatening stimuli were
      presented for 100 ms. Moreover, we observed significantly shorter (unwanted)
      fixations on threatening than on neutral peripheral stimuli, compatible with an
      avoidance bias, for longer presentation times. These findings demonstrate that,
      independent of trait anxiety levels, disengagement bias occurs without eye
      movements, whereas eye movements are implied in threat avoidance.

PMID- 26212203
TI  - Knee Osteoarthritis Worsening Across the Disease Spectrum and Future Knee Pain,
      Symptoms, and Functioning: A Multisite Prospective Cohort Study.
AB  - OBJECTIVE: Prognostic estimates for knee osteoarthritis worsening over the full
      disease spectrum have not been reported. Osteoarthritis Initiative data were used
      to determine the association between knee radiographic osteoarthritis worsening
      and future knee pain and function. METHODS: Yearly data over a 5-year period were
      analyzed. Outcome measures were the Western Ontario and McMaster Universities
      Osteoarthritis Index and the Knee Injury and Osteoarthritis Outcome Score pain
      and symptoms scales. Knees were grouped based on whether yearly Kellgren/Lawrence
      (K/L) grades worsened. Associations of yearly K/L worsening with knee pain,
      symptoms, or function scores at the end of the year and with lagged outcomes
      observed at least 1 year after worsening were assessed using linear models with
      generalized estimating equations. RESULTS: A total of 25,932 knee-years of
      observations were examined in the primary analysis. For knees with yearly K/L
      worsening, all outcome scores were significantly worse (P values from 0.02 to
      <0.001) at the end of the index year, as compared to unchanged knees. All
      outcomes for knees with worsened versus unchanged K/L scores exceeded the minimal
      clinically important difference (MCID). For lagged effects, outcomes at 1 year
      following the index K/L year exceeded the MCID and were statistically significant
      (P <= 0.001) for knees with baseline K/L grades of 2 or 3. CONCLUSION: K/L
      worsening over a 1-year period is prognostically important over the short term
      for all baseline K/L grades, and for knees with baseline K/L grades of 2 or 3
      worsening continues over the following year.

PMID- 26212204
TI  - In vitro standardization of two different removal devices in cemented implant
      prosthesis.
AB  - OBJECTIVES: The purpose of this study was to describe the force generated by two
      different removal devices used to retrieve cemented crowns on implant abutments.
      The influence of six different operators was evaluated. MATERIAL AND METHODS:
      Three replicated Coronaflex((r)) (Kaltenbach & Voigt GmbH, KaVo Dental GmbH) and
      reverse hammer setups were tested. The experimental setup has employed a screw
      bearing a diametral hole through which a loop holder passed. The screw was
      attached to a force transducer (Bruel & Kjaer, type 8201), and the loop holder
      arm was kept perpendicular to the transducer axis. The results were statistically
      evaluated with ANOVA. RESULTS: The operator has resulted to play significant
      influence with reference to reverse hammer (coefficient of variation 43.3%)
      rather than with Coronaflex((r)) (9.8%). Evaluating every single operator, more
      variation can still be found by considering each reverse hammer (37.5%) rather
      than each Coronaflex((r)) (8.8%). CONCLUSION: Coronaflex((r)) device was found to
      systematically reach a more repeatable and higher peak amplitude of forces
      compared with reverse hammer, both by experienced and inexperienced operators.

PMID- 26212206
TI  - DNA nanotechnology-enabled biosensors.
AB  - Biosensors employ biological molecules to recognize the target and utilize output
      elements which can translate the biorecognition event into electrical, optical or
      mass-sensitive signals to determine the quantities of the target. DNA-based
      biosensors, as a sub-field to biosensor, utilize DNA strands with short
      oligonucleotides as probes for target recognition. Although DNA-based biosensors
      have offered a promising alternative for fast, simple and cheap detection of
      target molecules, there still exist key challenges including poor stability and
      reproducibility that hinder their competition with the current gold standard for
      DNA assays. By exploiting the self-recognition properties of DNA molecules,
      researchers have dedicated to make versatile DNA nanostructures in a highly
      rigid, controllable and functionalized manner, which offers unprecedented
      opportunities for developing DNA-based biosensors. In this review, we will
      briefly introduce the recent advances on design and fabrication of static and
      dynamic DNA nanostructures, and summarize their applications for fabrication and
      functionalization of DNA-based biosensors. 

PMID- 26212207
TI  - Distribution of intestinal stem cell markers in colorectal precancerous lesions.
AB  - AIMS: Intestinal stem cell (ISC) markers such as LGR5, ASCL2, EPHB2 and OLFM4,
      and their clinical implications have been studied extensively in colorectal
      cancers (CRCs). However, little is known about their expression in precancerous
      lesions of CRCs. Here, we investigated the expression and distribution of ISC
      markers in serrated polyps and conventional adenomas. METHODS AND RESULTS:
      Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that
      all ISC markers were up-regulated significantly in conventional adenomas with low
      grade dysplasia (CALGs) compared with other lesions. RNA in-situ hybridization
      confirmed that CALGs exhibited strong and diffuse expression of all ISC markers,
      which indicate a stem cell-like phenotype. However, normal colonic mucosa,
      hyperplastic polyps and sessile serrated adenomas harboured LGR5(+) cells that
      were confined to the crypt base and demonstrated an organized expression of ISC
      markers. Notably, in traditional serrated adenomas, expression of LGR5 and ASCL2
      was localized to the ectopic crypts as in the normal crypts, but expression of
      EPHB2 and OLFM4 was distributed in a diffuse manner, which is suggestive of a
      progenitor-like features. CONCLUSIONS: The expression and distribution profile of
      ISC markers possibly provides insights into the organization of stem and
      progenitor-like cells in each type of precancerous lesion of CRC.

PMID- 26212208
TI  - Anticancer activity of Ophiobolin A, isolated from the endophytic fungus
      Bipolaris setariae.
AB  - The present work describes the anticancer activity of Ophiobolin A isolated from
      the endophytic fungus Bipolaris setariae. Ophiobolin A was isolated using
      preparative HPLC and its structure was confirmed by HRMS, (1)H NMR, (13)C NMR,
      COSY, DEPT, HSQC and HMBC. It inhibited solid and haematological cancer cell
      proliferation with IC50 of 0.4-4.3 MUM. In comparison, IC50 against normal cells
      was 20.9 MUM. It was found to inhibit the phosphorylation of S6 (IC50 = 1.9 +/-
      0.2 MUM), ERK (IC50 = 0.28 +/- 0.02 MUM) and RB (IC50 = 1.42 +/- 0.1 MUM), the
      effector proteins of PI3K/mTOR, Ras/Raf/ERK and CDK/RB pathways, respectively. It
      induced apoptosis and inhibited cell cycle progression in MDA-MB-231 cancer cells
      with concomitant inhibition of signalling proteins. Thus, this study reveals that
      anticancer activity of Ophiobolin A is associated with simultaneous inhibition of
      multiple oncogenic signalling pathways namely PI3K/mTOR, Ras/Raf/ERK and CDK/RB. 

PMID- 26212205
TI  - Glyconanomaterials for biosensing applications.
AB  - Nanomaterials constitute a class of structures that have unique physiochemical
      properties and are excellent scaffolds for presenting carbohydrates, important
      biomolecules that mediate a wide variety of important biological events. The
      fabrication of carbohydrate-presenting nanomaterials, glyconanomaterials, is of
      high interest and utility, combining the features of nanoscale objects with
      biomolecular recognition. The structures can also produce strong multivalent
      effects, where the nanomaterial scaffold greatly enhances the relatively weak
      affinities of single carbohydrate ligands to the corresponding receptors, and
      effectively amplifies the carbohydrate-mediated interactions. Glyconanomaterials
      are thus an appealing platform for biosensing applications. In this review, we
      discuss the chemistry for conjugation of carbohydrates to nanomaterials,
      summarize strategies, and tabulate examples of applying glyconanomaterials in in
      vitro and in vivo sensing applications of proteins, microbes, and cells. The
      limitations and future perspectives of these emerging glyconanomaterials sensing
      systems are furthermore discussed. 

PMID- 26212209
TI  - Binding of Yeast Cytochrome c to Forty-Four Charge-Reversal Mutants of Yeast
      Cytochrome c Peroxidase: Isothermal Titration Calorimetry.
AB  - Previously, we constructed, expressed, and purified 46 charge-reversal mutants of
      yeast cytochrome c peroxidase (CcP) and determined their electronic absorption
      spectra, their reaction with H2O2, and their steady-state catalytic properties [
      Pearl , N. M. et al. (2008) Biochemistry 47 , 2766 - 2775 ]. Forty-four of the
      mutants involve the conversion of either an aspartate or glutamate residue to a
      lysine residue, while two are positive-to-negative mutations, R31E and K149D. In
      this paper, we report on a calorimetric study of the interaction of each charge
      reversal mutant (excluding the internal mutants D76K and D235K) with recombinant
      yeast iso-1 ferricytochrome c(C102T) (yCc) under conditions where only one-to-one
      yCc/CcP complex formation is observed. Thirteen of the 44 surface-site charge
      reversal mutants decrease the binding affinity for yCc by a factor of 2 or more.
      Eight of the 13 mutations (E32K, D33K, D34K, E35K, E118K, E201K, E290K, E291K)
      occur within, or on the immediate periphery, of the crystallographically defined
      yCc binding site [ Pelletier , H. and Kraut , J. (1992) Science 258 , 1748 - 1755
      ], three of the mutations (D37K, E98K, E209K) are slightly removed from the
      crystallographic site, and two of the mutations (D165K, D241K) occur on the "back
      side" of CcP. The current study is consistent with a model for yCc binding to CcP
      in which yCc binds predominantly near the region defined by crystallographic
      structure of the 1:1 yCc-CcP complex, whether as a stable electron-transfer
      active complex or as part of a dynamic encounter complex.

PMID- 26212210
TI  - The snapping medial antebrachial cutaneous nerve.
AB  - Snapping elbow is a well-known condition where elbow flexion and extension
      elicits a painful, popping sensation. The most frequent etiology is anterior
      dislocation of the ulnar nerve over the medial epicondyle. Four patients (3
      females and 1 male) presented with complaints of a popping sensation in the
      elbow, pain over the medial aspect of the forearm, and ulnar neuritis. All
      patients underwent preoperative dynamic ultrasound and surgical exploration of
      the medial elbow. Intraoperatively, snapping of the MABC over the medial
      epicondyle was discovered in all four patients. In three patients, there was
      abnormal displacement of the medial triceps and ulnar nerve: in two of these,
      both structures dislocated over the medial epicondyle and in one patient both
      structures subluxated. In each case, the MABC was decompressed (n = 1) and
      transposed (n = 3), and in three cases, the medial triceps and ulnar nerve were
      addressed as well. Symptomatic improvement was achieved in all cases.
      Retrospective review of the ultrasound revealed the snapping MABC, though it was
      less effective prospectively in the cases when snapping MABC was not suspected.
      In conclusion, snapping of the MABC broadens the spectrum of disorders that
      results in snapping elbow. To our knowledge, we are unaware of prior reports of
      this entity.

PMID- 26212211
TI  - A Graphitic-C3N4 "Seaweed" Architecture for Enhanced Hydrogen Evolution.
AB  - A seaweed-like graphitic-C3N4 (g-C3N4 "seaweed") architecture has been prepared
      by direct calcination of the freeze-drying-assembled, hydrothermally treated
      dicyandiamide fiber network. The seaweed network of mesoporous g-C3N4 nanofibers
      is favorable for light harvesting, charge separation and utilization of active
      sites, and has highly efficient photocatalytic behavior for water splitting. It
      exhibits a high hydrogen-evolution rate of 9900 MUmol h(-1) g(-1) (thirty times
      higher than that of its g-C3N4 bulk counterpart), and a remarkable apparent
      quantum efficiency of 7.8% at 420 nm, better than most of the g-C3N4
      nanostructures reported. This work presents a very simple method for designing
      and developing high-performance catalysts for hydrogen evolution.

PMID- 26212212
TI  - Maternal eating disorder history and toddlers' neurodevelopmental outcomes: A
      brief report.
AB  - This study explored the neurodevelopmental outcomes of toddlers whose mothers
      have eating disorder histories and the contribution of maternal eating and
      comorbid psychopathology to the children's cognitive functioning. Twenty-nine
      mothers with prenatal eating disorders and their toddlers (18-42 months old) were
      compared to a case-control matched group of mothers with no eating
      psychopathology and their toddlers. Measures included current maternal eating and
      co-occurring psychopathology, and a developmental assessment of each child. The
      children of mothers with eating disorders showed delayed mental and psychomotor
      development. Severity of maternal eating disorder symptoms emerged as a
      significant predictor of child development, but other maternal psychopathology
      did not. Findings suggest that maternal eating disorder history may play a unique
      role in the development of neurodevelopmental functions in their children.

PMID- 26212213
TI  - Complete genome sequences and comparative genome analysis of Lactobacillus
      plantarum strain 5-2 isolated from fermented soybean.
AB  - Lactobacillus plantarum is an important probiotic and is mostly isolated from
      fermented foods. We sequenced the genome of L. plantarum strain 5-2, which was
      derived from fermented soybean isolated from Yunnan province, China. The strain
      was determined to contain 3114 genes. Fourteen complete insertion sequence (IS)
      elements were found in 5-2 chromosome. There were 24 DNA replication proteins and
      76 DNA repair proteins in the 5-2 genome. Consistent with the classification of
      L. plantarum as a facultative heterofermentative lactobacillus, the 5-2 genome
      encodes key enzymes required for the EMP (Embden-Meyerhof-Parnas) and
      phosphoketolase (PK) pathways. Several components of the secretion machinery are
      found in the 5-2 genome, which was compared with L. plantarum ST-III, JDM1 and
      WCFS1. Most of the specific proteins in the four genomes appeared to be related
      to their prophage elements. 

PMID- 26212214
TI  - Effects of Kyunghee Facial Resistance Program (KFRP) on mechanical and elastic
      properties of skin.
AB  - INTRODUCTION: Facial skin aging is influenced by weakened mimetic muscles.
      Resistance training of facial mimetic muscles could be one of practical strategy
      to defend against age-related changes. The aim of this study was to investigate
      the effects of an exercise program (KFRP: Kyunghee Facial Resistance Program)
      designed for facial mimetic muscles on the mechanical properties and elasticity
      of facial skin. METHODS: For this study, 16 healthy female volunteers aged 35-58
      participated in KFRP for eight weeks. The mechanical and elastic properties of
      skin were measured using a Cutometer(r) on the face and neck. RESULTS: The
      parameters representing skin fatigue decreased and the parameters representing
      skin elasticity increased significantly compared to the baseline in all measured
      regions. The ability of re-deformation of skin increased significantly except the
      zygomaticus and platysma muscle regions. All measured regions of skin became
      firmer and the ability to return to the initial position was also significantly
      improved compared to the baseline. Visco-elasticiy of the skin was not
      significantly altered. CONCLUSIONS: The skin became more firm and elastic through
      KFRP. This method of resistive exercise had a significantly positive influence on
      the mechanical properties and elasticity of facial and neck skin.

PMID- 26212215
TI  - Procalcitonin ratio and on-demand relaparotomy for septic peritonitis: validation
      of the focus index (FI).
AB  - PURPOSE: Secondary peritonitis remains challenging to manage and some recent
      evidence suggests that on-demand relaparotomy is more appropriate than planned
      relaparotomy. This study was designed to validate the predictive power of
      postoperative procalcitonin (PCT) changes in relation to elimination of the
      septic abdominal focus. METHODS: In this prospective trial, postoperative PCT
      serum levels were monitored in 234 surgical patients with secondary peritonitis.
      The PCT ratio on postoperative days (PODs) 1 and 2 (focus index; FI) was
      calculated and correlated with the success of the operation. RESULTS: A cutoff
      value of 1.1 was calculated for the FI. Values below 1.1 indicated insufficient
      elimination of the focus and values above 1.1 correlated with effective
      treatment. The optimal time for first PCT sampling was found to be 12-24 h after
      the index operation. After the respective data cleanup, successful elimination of
      the intraabdominal focus could be confirmed, with a sensitivity of 93 % and a
      specificity of 71 %. CONCLUSIONS: The FI is a single parameter-based reliable
      predictor of successful surgical eradication and strengthens the on-demand
      relaparotomy concept as the method of choice to treat secondary peritonitis.

PMID- 26212216
TI  - Molecular phylogeny supports S-chaetae as a key character better than jumping
      organs and body scales in classification of Entomobryoidea (Collembola).
AB  - The jumping organ (furcula) is the most characteristic structure among
      collembolans, and it is of great taxonomical values at higher levels. The largest
      superfamily Entomobryoidea is traditionally classified into four families only by
      the morphology of the furcula. Actually, many taxa among these families are
      strikingly similar in morphology without considering furcula. The phylogeny of
      Entomobryoidea was reconstructed here based on mitochondrial and ribosomal
      fragments. This indicated that both Paronellidae and Cyphoderidae were ingroups
      within Entomobryidae with the former polyphyletic. Topology tests, which used the
      likelihood and Bayesian approaches, also rejected the traditional hypotheses
      relying on furcula morphology. Further ancestral state reconstructions have
      revealed that traditional taxonomical characters, i.e., furcula and body scales,
      had multiple independent origins in Entomobryoidea whereas tergal specialized
      chaetae (S-chaetae) exhibited strong phylogenetic signals. By integrating both
      molecular and morphological evidence, the results of this study drastically
      undermine the present classification of Entomobryoidea. Tergal S-chaetotaxic
      pattern in combination with other characters are more reasonable in taxonomy at
      suprageneric levels than convergent furcula. This study provides new insights of
      the jumping organ, which could be adaptively modified during evolution of
      Collembola. 

PMID- 26212217
TI  - Molecular Modeling, Synthesis, and Anti-HIV Activity of Novel Isoindolinedione
      Analogues as Potent Non-nucleoside Reverse Transcriptase Inhibitors.
AB  - Different isoindolinedione derivatives bearing imine, amide, thioamide, and
      sulfonamide linkages have been designed in silico using discovery studio software
      (BIOVIA, San Diego, CA, USA), synthesized, and evaluated for their anti-HIV
      activity. SAR studies revealed that the linkages in these molecules did affect
      their anti-HIV activity and the molecules having sulfonamide linkages were the
      most potent HIV-RT inhibitors as the S=O bonds of the sulfonamide moiety
      interacted with Lys103 (NH or carbonyl or both) and Pro236; the NH part of the
      sulfonamide linkage formed bond with carbonyl of Lys101. blood-brain barrier
      (BBB) plots were also studied, and it was found that all the designed molecules
      have potential to cross BBB, a very vital criteria for anti-HIV drugs. In vitro
      screening was performed using HIV-1 strain IIIB in MT-4 cells using the MTT
      assay, and it was seen that some of these molecules were effective inhibitors of
      HIV-1 replication at nanomolar concentration with selectivity indices ranging
      from 33.75 to 73.33 under in vitro conditions. Some of these molecules have shown
      good anti-HIV activity at 3-4 nm concentrations. These derivatives have potential
      to be developed as lead molecules effective against HIV-1. Novel isoindolinedione
      derivatives as probable NNRTIs have been synthesized and characterized. Some of
      these molecules have shown good anti-HIV activity at 3-4 nm concentrations. 

PMID- 26212218
TI  - Longitudinal trajectories of bicultural identity integration in recently
      immigrated Hispanic adolescents: Links with mental health and family functioning.
AB  - This study examined, in a sample of recently immigrated Hispanic adolescents in
      Miami and Los Angeles, the extent to which bicultural identity integration (BII;
      involving the ability to synthesise one's heritage and receiving cultural streams
      and to identify as a member of both cultures) is best understood as a
      developmental construct that changes over time or as an individual-difference
      construct that is largely stable over time. We were also interested in the extent
      to which these trajectories predicted mental health and family functioning.
      Recent-immigrant 9th graders (N = 302) were assessed 6 times from 9th to 12th
      grade. Latent class growth analyses using the first 5 timepoints identified 2
      trajectory classes-one with lower BII scores over time and another with higher
      BII scores over time. Higher heritage and US identity at baseline predicted
      membership in the higher BII class. At the 6th study timepoint, lower BII
      adolescents reported significantly poorer self-esteem, optimism, prosocial
      behaviour and family relationships compared with their higher BII counterparts.
      These findings are discussed in terms of further research on the over-time
      trajectory of biculturalism, and on the need to develop interventions to promote
      BII as a way of facilitating well-being and positive family functioning. 

PMID- 26212220
TI  - Improving patient satisfaction: Timely feedback to specific physicians is
      essential for success.

PMID- 26212221
TI  - Evolution of vertebrate adaptive immunity: immune cells and tissues, and
      AID/APOBEC cytidine deaminases.
AB  - All surviving jawed vertebrate representatives achieve diversity in
      immunoglobulin-based B and T cell receptors for antigen recognition through
      recombinatorial rearrangement of V(D)J segments. However, the extant jawless
      vertebrates, lampreys and hagfish, instead generate three types of variable
      lymphocyte receptors (VLRs) through a template-mediated combinatorial assembly of
      different leucine-rich repeat (LRR) sequences. The clonally diverse VLRB
      receptors are expressed by B-like lymphocytes, while the VLRA and VLRC receptors
      are expressed by lymphocyte lineages that resemble alphabeta and gammadelta T
      lymphocytes, respectively. These findings suggest that three basic types of
      lymphocytes, one B-like and two T-like, are an essential feature of vertebrate
      adaptive immunity. Around 500 million years ago, a common ancestor of jawed and
      jawless vertebrates evolved a genetic program for the development of prototypic
      lymphoid cells as a foundation for an adaptive immune system. This acquisition
      preceded the convergent evolution of alternative types of clonally diverse
      receptors for antigens in all vertebrates, as reviewed in this article. 

PMID- 26212219
TI  - Immunological evaluation of peptide vaccination for cancer patients with the HLA
      A26 allele.
AB  - To develop a peptide vaccine for cancer patients with the HLA-A26 allele, which
      is a minor population worldwide, we investigated the immunological responses of
      HLA-A26(+) /A26(+) cancer patients to four different CTL epitope peptides under
      personalized peptide vaccine regimens. In personalized peptide vaccine regimens,
      two to four peptides showing positive peptide-specific IgG responses in pre
      vaccination plasma were selected from the four peptide candidates applicable for
      HLA-A26(+) /A26(+) cancer patients and administered s.c. Peptide-specific CTL and
      IgG responses along with cytokine levels were measured before and after
      vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also
      measured. In this study, 21 advanced cancer patients, including seven lung, three
      breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA-A26
      genotypes were HLA-A26:01 (n = 24), HLA-A26:03 (n = 10), and HLA-A26:02 (n = 8).
      One, 14, and 6 patients received two, three, and four peptides, respectively.
      Grade 1 or 2 skin reactions at the injection sites were observed in the majority
      of patients, but no severe adverse events related to the vaccination were
      observed. Peptide-specific CTL responses were augmented in 39% or 22% of patients
      after one or two cycles of vaccination, respectively. Notably, peptide-specific
      IgG were augmented in 63% or 100% of patients after one or two cycles of
      vaccination, respectively. Personalized peptide vaccines with these four CTL
      epitope peptides could be feasible for HLA-A26(+) advanced cancer patients
      because of their safety and higher rates of immunological responses.

PMID- 26212222
TI  - Weissella oryzae DC6-facilitated green synthesis of silver nanoparticles and
      their antimicrobial potential.
AB  - Nanoparticles and nanomaterials are at the prominent edge of the rapidly
      developing field of nanotechnology. Recently, nanoparticle synthesis using
      biological resources has been found to be a new area with considerable prospects
      for development. Biological systems are the masters of ambient condition
      chemistry and are able to synthesize nanoparticles by utilizing metal salts. In
      the perspective of the current initiative to develop green technologies for the
      synthesis of nanoparticles, microorganisms are of considerable interest. Thus,
      the present study describes a bacterial strain-Weissella oryzae DC6-isolated from
      mountain ginseng, for the green and facile synthesis of silver nanoparticles. The
      particles were synthesized effectively without the need for any supplementary
      modification to maintain stability. The synthesized nanoparticles were evaluated
      by several instrumental techniques, comprising ultraviolet-visible
      spectrophotometry, field emission transmission electron microscopy, energy
      dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction, and dynamic
      light scattering. In addition, the biosynthesized silver nanoparticles were
      explored for their antimicrobial activity against clinical pathogens including
      Vibrio parahaemolyticus, Bacillus cereus, Bacillus anthracis, Staphylococcus
      aureus, Escherichia coli, and Candida albicans. Furthermore, the potential of
      nanoparticles has been observed for biofilm inhibition against Staphylococcus
      aureus and Pseudomonas aeruginosa. Thus, the synthesis of silver nanoparticles by
      the strain W. oryzae DC6 may serve as a simple, green, cost-effective,
      consistent, and harmless method to produce antimicrobial silver nanoparticles. 

PMID- 26212223
TI  - Primary biliary cirrhosis: safety and benefits of established and emerging
      therapies.
AB  - INTRODUCTION: Primary biliary cirrhosis (PBC) is a chronic, cholestatic liver
      disease characterized histologically by lymphocytic cholangitis and intralobular
      bile duct destruction. It is a progressive disorder associated with increased
      mortality and decreased quality of life related to hepatic fibrosis, troublesome
      symptoms such as fatigue and pruritus, and ultimately endstage cirrhosis. PBC
      affects adults around the world, and therefore effective treatment of PBC and its
      associated symptoms constitute significant issues for patients and providers as
      well as on a public health level. The only approved pharmacotherapy for PBC to
      date is ursodeoxycholic acid (UDCA), a choleretic, hydrophilic bile acid which
      has been in clinical use for decades. UDCA is effective in a majority of patients
      with PBC, but nearly a third of patients are UDCA non-responders. Non-response to
      UDCA is associated with an increased risk of death or need for liver
      transplantation (LT). Whereas LT is an effective treatment, it engenders
      substantial cost and a risk of PBC recurrence, among other complications.
      Patients who are non-responders to UDCA or have highly symptomatic disease (e.g.,
      intractable pruritus) are thus in critical need of novel therapeutic approaches,
      which are both safe and effective. AREAS COVERED: In this review, we provide a
      synopsis regarding the safety and benefits of established and emerging
      pharmacotherapies for PBC and present viewpoints on how they may evolve over the
      next several years. EXPERT OPINION: It is our belief that the pharmacoscope of
      PBC, as with other cholestatic liver diseases, is likely to see important
      advancements in the near future.

PMID- 26212224
TI  - Exertional rhabdomyolysis associated with high intensity exercise.

PMID- 26212225
TI  - Cysteine Prevents the Reduction in Keratin Synthesis Induced by Iron Deficiency
      in Human Keratinocytes.
AB  - L-cysteine is currently recognized as a conditionally essential sulphur amino
      acid. Besides contributing to many biological pathways, cysteine is a key
      component of the keratin protein by its ability to form disulfide bridges that
      confer strength and rigidity to the protein. In addition to cysteine, iron
      represents another critical factor in regulating keratins expression in epidermal
      tissues, as well as in hair follicle growth and maturation. By focusing on human
      keratinocytes, the aim of this study was to evaluate the effect of cysteine
      supplementation as nutraceutical on keratin biosynthesis, as well as to get an
      insight on the interplay of cysteine availability and cellular iron status in
      regulating keratins expression in vitro. Herein we demonstrate that cysteine
      promotes a significant up-regulation of keratins expression as a result of de
      novo protein synthesis, while the lack of iron impairs keratin expression.
      Interestingly, cysteine supplementation counteracts the adverse effect of iron
      deficiency on cellular keratin expression. This effect was likely mediated by the
      up-regulation of transferrin receptor and ferritin, the main cellular proteins
      involved in iron homeostasis, at last affecting the labile iron pool. In this
      manner, cysteine may also enhance the metabolic iron availability for DNA
      synthesis without creating a detrimental condition of iron overload. To the best
      of our knowledge, this is one of the first study in an in vitro keratinocyte
      model providing evidence that cysteine and iron cooperate for keratins
      expression, indicative of their central role in maintaining healthy epithelia.

PMID- 26212226
TI  - Gas Transfer Controls Carbon Limitation During Biomass Production by Marine
      Microalgae.
AB  - This study presents the first in-depth analysis of CO2 limitation on the biomass
      productivity of the biofuel candidate marine microalga Nannochloropsis oculata.
      Net photosynthesis decreased by 60% from 125 to 50 MUmol O2 L(-1)h(-1) over a 12
      h light cycle as a direct result of carbon limitation. Continuous dissolved O2
      and pH measurements were used to develop a detailed diurnal mechanism for the
      interaction between photosynthesis, gas exchange and carbonate chemistry in the
      photo-bioreactor. Gas exchange determined the degree of carbon limitation
      experienced by the algae. Carbon limitation was confirmed by delivering more CO2
      , which increased net photosynthesis back to its steady-state maximum. This study
      highlights the importance of maintaining replete carbon concentrations in photo
      bioreactors and other culturing facilities, either by constant pH operation or
      preferably by designing a feedback loop based on the dissolved O2 concentration.

PMID- 26212227
TI  - A Morphological Transition of Inverse Mesophases of a Branched-Linear Block
      Copolymer Guided by Using Cosolvents.
AB  - We report here a strategy for influencing the phase and lattice of the inverse
      mesophases of a single branched-linear block copolymer (BCP) in solution which
      does not require changing the structure of the BCP. The phase of the self
      assembled structures of the block copolymer can be controlled ranging from
      bilayer structures of positive curvature (polymersomes) to inverse mesophases
      (triply periodic minimal surfaces and inverse hexagonal structures) by adjusting
      the solvent used for self-assembly. By using solvent mixtures to dissolve the
      block copolymer we were able to systematically change the affinity of the solvent
      toward the polystyrene block, which resulted in the formation of inverse
      mesophases with the desired lattice by self-assembly of a single branched-linear
      block copolymer. Our method was also applied to a new solution self-assembly
      method for a branched-linear block copolymer on a stationary substrate under
      humidity, which resulted in the formation of large mesoporous films. Our results
      constitute the first controlled transition of the inverse mesophases of block
      copolymers by adjusting the solvent composition. 

PMID- 26212228
TI  - Association between methylenetetrahydrofolate reductase C677T polymorphism and
      psoriasis: A meta-analysis.
AB  - Several studies have evaluated the associations between methylenetetrahydrofolate
      reductase (MTHFR) C677T and psoriasis. However, the results remain inconclusive.
      The objective of the present study was to conduct a qualitative and quantitative
      meta-analysis investigating the associations between MTHFR C677T and psoriasis. A
      published work search of PubMed, Embase, Web of Science and Chinese National
      Knowledge Infrastructure database were conducted to identify all publications
      concerning MTHFR C677T polymorphism and psoriasis on 1 October 2014. The
      principal outcome measure for evaluating the strength of the association was
      crude odds ratios along with their corresponding 95% confidence intervals. Data
      were extracted and statistical analyses were implemented using STATA version 12.0
      software. A total of 1179 psoriatic cases and 937 controls from five case-control
      studies concentrating on the association between MTHFR C677T polymorphism and
      psoriasis were included in this qualitative meta-analysis. Pooled analysis
      revealed that there is no association between this polymorphism and
      susceptibility to psoriasis in dominant, recessive, allele and additive models
      under a random-effect model. However, a marginal significant association was
      found in the overdominant model under fixed-effect model. Subgroup analysis of
      ethnicity demonstrated that there is no association between MTHFR C677T
      polymorphism and either Asian or European psoriatic patients. In conclusion,
      MTHFR C677T polymorphism, qualitatively, is not a genetic factor for the
      pathogenesis of psoriasis but could quantitatively reflect the severity of
      psoriasis to some extent. 

PMID- 26212229
TI  - Response to the letter "What is the role of ADHD symptoms in obesity affecting
      cognitive outcome?".

PMID- 26212230
TI  - Comparison between home and hospital set-up for unattended home-based
      polysomnography: a prospective randomized study.
AB  - BACKGROUND: Unattended home-based polysomnography (H-PSG) is a reliable tool for
      the diagnosis of obstructive sleep apnoea (OSA). The quality of the recording can
      be influenced by several factors including the set-up location - at home versus
      in the sleep laboratory. Previous studies have suggested that the failure rate is
      higher when H-PSG is fitted in hospital. The aim of this study was to determine
      the influence of hook-up location on H-PSG recording quality. Feasibility and
      repeatability of H-PSG were also assessed. METHODS: Consecutive patients
      suspected of OSA were selected. Each patient underwent two H-PSGs within two
      weeks, one fitted at home and one fitted in the sleep laboratory. The order of H
      PSG was randomly assigned. RESULTS: Among the 102 included patients, 95 completed
      the study. Ninety-three per cent of the 190 H-PSGs were satisfactory. The failure
      rate of H-PSG was similar for both the home set-up and the sleep laboratory set
      up (p = 0.33). Seventy-nine per cent of patients opted to be fitted at home. OSA
      was diagnosed in 59%. The apnoea-hypopnoea index was similar for home and sleep
      laboratory set-up, resulting in a very good reproducibility (intraclass
      correlation coefficient of 0.85). No differences in total sleep time and sleep
      architecture were observed in both set-up protocols. Except for sleep duration,
      which was longer in the first H-PSG test, we did not observe any first-night
      effect during the first H-PSG. CONCLUSION: The present study demonstrates that
      hospital hook-up is as effective as home hook-up for home-unattended
      polysomnography, and that feasibility and repeatability of H-PSG are very good.

PMID- 26212231
TI  - Association between sleep-disordered breathing, obstructive sleep apnea, and
      cancer incidence: a systematic review and meta-analysis.
AB  - OBJECTIVE/BACKGROUND: Via this systematic review and meta-analysis, we assessed
      the associatio between sleep-disordered breathing (SDB)/obstructive sleep apnea
      (OSA) and cancer incidence. METHOD: Medline, Embase, Cochrane Central, and
      electronic databases were searched for relevant studies in any language. Studies
      were included based on the following criteria: (1) those on patients with
      SDB/OSA, (2) those reporting cancer incidence rates specific to patients with
      SDB/OSA, and (3) those defining SDB/OSA using sleep-study-based objective
      measures. The quality of the included studies was assessed using the Newcastle
      Ottawa Quality Assessment Scale (NOQA). RESULTS: Of the 8766 retrieved citations,
      five studies that defined SDB/OSA using the apnea-hypopnea index (AHI) or the
      respiratory disturbance index (RDI) totaling 34,848 patients with SDB and 77,380
      patients without SDB were pooled into a meta-analysis. All five studies were of
      good quality (NOQA >= 6). A total of 574 (1.6%) and 290 (0.37%) incident cancers
      were reported in patients with and without SDB, respectively. In the unadjusted
      analysis, patients with SDB/OSA were at an increased risk of incident cancer
      (relative risk [RR]: 1.53, 95% confidence interval [CI]: 1.31-1.79, P <0.001,
      I(2): 0, five included studies). When adjusted for traditional cancer risk
      factors, the association between SDB/OSA and cancer incidence, although
      attenuated (RR: 1.40, 95% CI: 1.01-1.95, P = 0.04, I(2): 60%, five included
      studies), remains significant. CONCLUSIONS: SDB/OSA may increase the risk of
      incident cancer. Inferring an independent association is not possible from our
      analysis considering the retrospective cohort design of the included studies and
      high inter-study heterogeneity. An individual patient data meta-analysis would
      help validate our findings.

PMID- 26212232
TI  - What is the role of ADHD symptoms in obesity affecting cognitive outcomes?

PMID- 26212233
TI  - Alpha-mannosidosis: characterization of CNS pathology and correlation between CNS
      pathology and cognitive function.
AB  - Alpha-mannosidosis (AM) (OMIM 248500) is a rare lysosomal storage disease. The
      understanding of the central nervous system (CNS) pathology is limited. This
      study is the first describing the CNS pathology and the correlation between the
      CNS pathology and intellectual disabilities in human AM. Thirty-four patients,
      aged 6-35 years, with AM were included. Data from 13 healthy controls were
      included in the analysis of the magnetic resonance spectroscopy (MRS).
      Measurements of CNS neurodegeneration biomarkers in cerebrospinal fluid (CSF),
      CSF-oligosaccharides, and performance of cerebral magnetic resonance imaging
      (MRI) and MRS were carried out. On MRI, 5 of 10 patients had occipital white
      matter (WM) signal abnormalities, and 6 of 10 patients had age-inappropriate
      myelination. MRS demonstrated significantly elevated mannose complex in gray
      matter and WM. We found elevated concentrations of tau-protein, glial fibrillary
      acidic protein and neurofilament light protein in 97 patients, 74% and 41% of CSF
      samples, respectively. A negative correlation between CSF-biomarkers and
      cognitive function and CSF-oligosaccharides and cognitive function was found. The
      combination of MRS/MRI changes, elevated concentrations of CSF-biomarkers and CSF
      oligosaccharides suggests gliosis and reduced myelination, as part of the CNS
      pathology in AM. Our data demonstrate early neuropathological changes, which may
      be taken into consideration when planning initiation of treatment.

PMID- 26212234
TI  - Effect of Admission Glasgow Coma Scale Motor Score on Neurological Outcome in Out
      of-Hospital Cardiac Arrest Patients Receiving Therapeutic Hypothermia.
AB  - BACKGROUND: Because the initial (on admission) Glasgow Coma Scale (GCS)
      examination has not been fully evaluated in comatose survivors of cardiac arrest
      (CA) who receive therapeutic hypothermia (TH), the aim of the present study was
      to determine any association between the admission GCS motor score and neurologic
      outcomes in patients with out-of-hospital CA who receive TH. METHODS AND RESULTS:
      In the J-PULSE-HYPO study registry, patients with bystander-witnessed CA were
      eligible for inclusion. Patients were divided into 3 groups based on GCS motor
      score (1, 2-3, and 4-5) to assess various effects on neurologic outcome.
      Univariate and multivariate analyses were performed to identify independent
      predictors of good neurologic outcome at 90 days. Of 452 patients, 302 were
      enrolled. There was a significant difference among the 3 patient groups with
      regard to neurologic outcome at 90 days in the univariate analysis. Multiple
      logistic regression analyses showed that the GCS motor score on admission, age
      >65 years, bystander cardiopulmonary resuscitation, the time from collapse to
      return of spontaneous circulation, and pupil size <4 mm were independent
      predictors of a good neurologic outcome at 90 days in cases of CA (GCS motor
      score, 4-5: odds ratio, 8.18; 95% confidence interval: 1.90-60.28; P<0.01).
      CONCLUSIONS: GCS motor score is an independent predictor of good neurologic
      outcome at 90 days in patients sustaining out-of-hospital CA who receive TH.

PMID- 26212236
TI  - DISC1 regulates expression of the neurotrophin VGF through the PI3K/AKT/CREB
      pathway.
AB  - Disrupted in schizophrenia (DISC1) is a risk factor for chronic mental disease.
      In a previous proteomic study, we reported that knocking down DISC1 results in a
      sharp decrease in the levels of the neuropeptide precursor VGF (non-acronymic)
      and leads to reduced activation of cAMP response element-binding protein (CREB)
      and protein kinase B (AKT) in neurons. The main objective of this study is to
      complete the characterization of the route, or routes, involving AKT and CREB
      through which DISC1 modulates the expression of VGF. For that we explored known
      players upstream of AKT and the DISC1 binding partners glycogen synthase kinase-3
      beta and Phosphodiesterase-4, which might in turn reach out to CREB in murine
      neuron primary culture. We found that DISC1 modulates the activation of
      Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). Furthermore,
      pharmacological inhibition of PI3K resulted in decreased expression of VGF. All
      this suggests that the PI3K/AKT pathway plays a role in mediating the effects of
      DISC1 silencing on VGF expression. Given the important roles of VGF in mental
      disease, and its drugability, the DISC1-VGF connection might prove to be
      important for efforts to develop new therapies for these diseases.

PMID- 26212237
TI  - Blue-emitting heteroleptic Ir(III) phosphors with functional 2,3'-bipyridine or 2
      (pyrimidin-5-yl)pyridine cyclometalates.
AB  - We have synthesized four Ir(iii) metal complexes () bearing dual fluorine-free
      cyclometalates that are derived from 2',6'-dimethoxy-4-t-butyl-2,3'-bipyridine
      (pypy)H or 2-(2,4-dimethoxypyrimidin-5-yl)-4-t-butylpyridine (pmpy)H and a third
      ancillary, e.g. 5-pyridin-2-yl-pyrazolate (Pz) or 5-pyridin-2-yl-pyrrolide (Pr),
      respectively. The Ir(iii) complexes and were examined by X-ray diffraction
      studies for providing the structural proofs. Photophysical properties were next
      measured in CH2Cl2 at RT, among which the pypy complexes and showed an identical
      structured emission with an E0-0 peak located at 458 nm, while the corresponding
      pmpy derivative displayed the most blue-shifted E0-0 peak at 444 nm. Organic
      light-emitting diodes (OLEDs) were fabricated using multiple layered architecture
      and the aforementioned phosphor at 8 wt% doping level. The associated OLED
      performances, cf. max. E.Q.E. = 9.0%, 14.3%, 5.8% and 9.4% and CIEx,y coordinates
      at (0.16, 0.22), (0.16, 0.24), (0.16, 0.17) and (0.16, 0.20) at 100 cd m(-2) for
      phosphors in sequence, confirmed their potential to act as blue dopants for
      phosphorescent OLEDs. 

PMID- 26212235
TI  - A phospholipid uptake system in the model plant Arabidopsis thaliana.
AB  - Plants use solar energy to produce lipids directly from inorganic elements and
      are not thought to require molecular systems for lipid uptake from the
      environment. Here we show that Arabidopsis thaliana Aminophospholipid ATPase10
      (ALA10) is a P4-type ATPase flippase that internalizes exogenous phospholipids
      across the plasma membrane, after which they are rapidly metabolized. ALA10
      expression and phospholipid uptake are high in the epidermal cells of the root
      tip and in guard cells, the latter of which regulate the size of stomatal
      apertures to modulate gas exchange. ALA10-knockout mutants exhibit reduced
      phospholipid uptake at the root tips and guard cells and are affected in growth
      and transpiration. The presence of a phospholipid uptake system in plants is
      surprising. Our results suggest that one possible physiological role of this
      system is to internalize lysophosphatidylcholine, a signalling lipid involved in
      root development and stomatal control. 

PMID- 26212238
TI  - Organic salts and aromatic substrates in two-component gel phase formation: the
      study of properties and release processes.
AB  - To identify gel phases able to act as confined reaction media or materials for
      the removal of organic pollutants, we studied two-component gel phases formed by
      naphthalenedisulfonate diimidazolium salts in the presence of some organic
      guests, in 1-propanol solution. Guests differing in pi-surface area, bulkiness
      and electronic properties were taken into account. Soft materials obtained were
      investigated for their thermal stability, self-repairing ability and morphology.
      Furthermore, two-component gel phase formation was studied using resonance light
      scattering (RLS) measurements. Guest release processes from the gel phase were
      also studied. These processes were monitored as a function of time using both UV
      vis and RLS measurements and considering important parameters such as the gelator
      concentration, the nature of extraction solvent and the extension of contact
      surface area between solvent and gel phase. Data collected shed light on the
      properties of the two-component gels and could represent a useful tool to better
      plan the application of these soft materials. 

PMID- 26212239
TI  - Orexigenic Gene Expression in Late Gestation Ovine Foetal Hypothalamus is
      Sensitive to Maternal Undernutrition and Realimentation.
AB  - Adverse nutritional effects on developing foetal hypothalamic appetitive pathways
      may contribute to programmed hyperphagia and obesity in intra-uterine growth
      restricted, low birth weight offspring. In the present study, for the first time,
      hypothalamic gene expression for primary orexigenic and anorexigenic genes was
      examined in late gestation ovine foetuses (130 days; term=145 days) whose mothers
      were undernourished (UN) or well-nourished (C) throughout pregnancy, or
      transferred from UN to C on day 90 (UN-C). Pregnancies resulted from singleton
      embryo transfer into adolescent growing ewes. Body weight, carcass fat content
      and perirenal adipose tissue (PAT) mass were all lower for UN (n=9) than C (n=7)
      and intermediate for UN-C foetuses (n=6), with no effect of sex. PAT leptin gene
      expression (by the reverse transcriptase-polymerase chain reaction) was lower in
      UN than C and UN-C groups, and lower in males than females. Gene expression (by
      in situ hybridisation with radiolabelled riboprobes) in the arcuate nucleus was
      greater in UN than C foetuses for neuropeptide Y (NPY), agouti-related peptide
      (AGRP) and leptin receptor (OBRb) but not different for pro-opiomelanocortin and
      cocaine- and amphetamine-regulated transcript. Gene expression in UN-C foetuses
      was intermediate for NPY and AGRP and not different from C foetuses for OBRb.
      Gene expression for NPY, AGRP and OBRb correlated negatively with foetal carcass
      fat content and with PAT leptin gene expression across all groups. Males had
      greater mRNA expression for AGRP than females, with NPY and OBRb showing similar
      trends. Therefore, maternal undernutrition throughout pregnancy increased
      orexigenic gene expression in the late gestation foetal hypothalamus, and
      expression levels were largely normalised by improved maternal nutrition in the
      last third of pregnancy. These findings may have implications for avoiding or
      correcting prenatal programming of postnatal hyperphagia and obesity.

PMID- 26212240
TI  - Styles of Counterfactual Thoughts in People with and without Signs of Depression.
AB  - People in a depressive state frequently believe that things could have happened
      differently in their lives, which is regarded as counterfactual thought. This
      study aimed to investigate whether the styles of counterfactual thought shown by
      people with indicating signs of depression and by people without any of those
      signs are different. Study participants were 42 adults divided into two groups:
      those with signs of depression and those without signs of depression. Five
      stories taken from newspapers and magazines and fictional scenarios were
      presented to the participants. After reading such stories, participants had to
      answer questions about how the narrated facts could have been different from what
      they actually were. Results indicated similar counterfactual thought styles in
      both groups (with and without depression signs). Most of the thoughts found were
      categorized as upward, subtractive, self-referent and that modified an aspect
      referred to action/inaction. A few significant differences between groups were
      observed, and most of them were obtained through directed modifications, in the
      last three stories. Some tendencies were shown in the group of people with signs
      of depression, such as those found for the subtractive category, t(40) = 2.33, p
      < .05, which can indicate a trend of possible failure in the preparatory function
      of CT, and in the hetero-referral function, t(40) = 1.97, p < .05, indicating a
      difficulty in thinking of different forms of action in the future. The removal of
      negative events may indicate that these experiences are not beneficial to
      people's survival. These results may indicate some tendencies about how people in
      depressive states think about past events. 

PMID- 26212241
TI  - Fasted Exercise and Increased Dietary Protein Reduces Body Fat and Improves
      Strength in Jockeys.
AB  - The present study assessed the effects of a diet and exercise intervention in
      jockeys on body composition, metabolism, bone and mental health. 10 jockeys
      followed an individually prescribed 6-wk diet (Carbohydrate=2.5-3.5 g/kg,
      Protein=2.5 g/kg, Fat=1.0 g/kg). Body mass (59.2+/-4.6 vs. 57.6+/-4.5 kg), fat
      mass (7.5+/-3.5 vs. 6.2+/-2.6) and body fat (13.1+/-5.9 vs. 11.5+/-4.9%) all
      decreased (P<0.05) from pre to post-intervention whilst lean mass (47.1+/-5.3 vs.
      47.0+/-5.5 kg) was maintained (P=0.80). RMR (1703+/-329 vs. 1975+/-313 kcal.d(
      1)), VO2max (3.8+/-0.8 vs. 4.1+/-0.7 L/min(- 1)) chest strength (65+/-11 vs. 71+/
      13 kg), leg strength (160+/-28 vs. 175+/-29 kg) and jumping height (40+/-6 vs.
      48+/-5 cm) significantly increased (P<0.05). Bone health (DXA) did not change
      (P>0.05) at hip (-1.04+/-1.29 vs. - 0.76+/-0.71) or lumbar sites (-1.32+/-0.76
      vs. - 1.31+/-0.77). Psychometrics (GHQ-12 and EAT-26) remained unchanged (10.3+/
      4.3 vs. 8.9+/-3.8 and 14.8+/-9.6 vs. 11.0+/-5.6, P>0.05, respectively). This
      approach represents a marked difference from jockeys' habitual weight-making that
      largely involves dehydration and food deprivation.

PMID- 26212242
TI  - The Effect of Lateral Ankle Ligament Repair in Muscle Reaction Time in Patients
      with Mechanical Ankle Instability.
AB  - Studies have shown that functional ankle instability can result in prolonged
      muscle reaction time. However, the deficit in muscle reaction time in patients
      with mechanical ankle instability (MAI) and the effect of lateral ankle ligament
      repair on muscle reaction time are unclear. The purpose of this study was to
      identify the deficit in muscle reaction time, and to evaluate the role of lateral
      ligament repair in improving muscle reaction time in MAI patients. Sixteen MAI
      patients diagnosed with lateral ankle ligament tears by ultrasonography and
      magnetic resonance imaging underwent arthroscopic debridement and open lateral
      ankle ligament repair with a modified Brostrom procedure. One day before the
      operation, reaction times of the tibialis anterior and peroneus longus muscles
      were recorded following sudden inversion perturbation while walking on a custom
      walkway, and anterior drawer test (ADT) and American Orthopaedic Foot and Ankle
      Society (AOFAS) scale score were evaluated. Six months postoperatively, muscle
      reaction time, ADT and AOFAS scale score were reevaluated, and muscle reaction
      times in 15 healthy controls were also recorded. Preoperatively, the affected
      ankles in the MAI group had significantly delayed tibialis anterior and peroneus
      longus muscles reaction times compared with controls. Six months after the
      operation, median AOFAS scale scores were significantly greater than
      preoperatively, and ADT was negative in the MAI group. However, the affected
      ankles in the MAI group showed no difference in muscle reaction time compared
      with preoperative values. MAI patients had prolonged muscle reaction time. The
      modified Brostrom procedure produced satisfactory clinical outcomes in MAI
      patients, but did not shorten reaction times of the tibialis anterior and
      peroneus longus muscles. 

PMID- 26212243
TI  - Musculoskeletal Health, Kidney and Liver Function in Retired Jockeys.
AB  - The long-term implications of making-weight daily on musculoskeletal health and
      functioning of the kidney and liver remain unknown. This study aimed to
      investigate musculoskeletal health and kidney and liver function in a group of
      retired jockeys. 28 retired male jockeys (age 50-70 years) provided fasting blood
      samples for markers of bone metabolism and kidney and liver function. A dual
      energy x-ray absorptiometry (DXA) scan was performed for the assessment of bone
      mineral density (BMD). Established reference ranges were used for interpretation
      of results. Comparisons were made between retired jockeys based on the
      professional racing licence held: Flat, National Hunt or Dual. Mean whole-body
      osteopenia was reported, with no differences between groups. Bone markers,
      micronutrients, electrolytes and associated hormones, and markers for kidney and
      liver function were within clinical normative ranges. No differences existed
      between groups. Results indicate the retired jockeys in this study do not
      demonstrate compromised bone health or kidney and liver function. However, the
      retired jockeys may not have undergone chronic weight cycling in the extreme
      manner evident in present-day jockeys, indicating the next generation of jockeys
      may face more of a problem. Jockeys should be tracked longitudinally throughout
      their racing career and beyond. 

PMID- 26212244
TI  - Lower Body vs. Upper Body Resistance Training and Arterial Stiffness in Young
      Men.
AB  - Resistance training has been shown to increase arterial stiffness. The purpose of
      the present study was to examine and compare the systemic arterial stiffness
      responses to acute lower body (LRT) and upper body (URT) resistance training. 20
      healthy young men [median age: 26 years (interquartile range 23, 32)] underwent
      LRT, URT and whole body resistance training (WRT). Before and immediately after,
      as well as 20, 40 and 60 min after each training session, we measured the cardio
      ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV) using
      VaSera VS-1500 N. We used mixed models for repeated measurements to estimate the
      post-exercise differences in CAVI and baPWV between the 3 resistance training
      modes. Immediately after exercise cessation, both CAVI and baPWV were lower for
      LRT compared with URT [CAVI: - 0.93 (95% confidence interval [CI] - 1.15, -
      0.70); baPWV: - 2.08 m/s (95% CI - 2.48, - 1.67)]. Differences between LRT and
      URT gradually decreased during follow-up. Compared with WRT, LRT induced a
      decrease and URT an increase in arterial stiffness across all time points. In
      conclusion, LRT presents more favorable post-exercise arterial stiffness than
      URT. Our results suggest that LRT or WRT may be preferred over URT in individuals
      with impaired arterial stiffness.

PMID- 26212245
TI  - BDNF, IGF-I, Glucose and Insulin during Continuous and Interval Exercise in Type
      1 Diabetes.
AB  - Type 1 diabetes (T1D) can have a significant impact on brain function, mostly
      ascribed to episodes of hypoglycemia and chronic hyperglycemia. Exercise has
      positive effects on acute and chronic glycemic control in T1D, and has beneficial
      effects on cognitive function by increasing neurotrophins such as BDNF and IGF-I
      in non-diabetic humans. The present study examines the effects of different types
      of exercise intensities on neurotrophins in T1D. 10 participants with type 1
      diabetes were evaluated in 3 sessions: high-intensity exercise (10*[60 s 90%Wmax,
      60 s 50 W]), continuous exercise (22 min, 70% VO2 max) and a control session.
      Blood glucose, serum free insulin, serum BDNF and IGF-I were assessed pre/post
      all the trials and after recovery. Blood glucose significantly decreased after
      both exercise intensities and BDNF levels increased, with a dose-response effect
      for exercise intensity on BDNF. IGF-I changed over time, but without a difference
      between the different exercise protocols. Both exercise intensities change
      neurotrophins in T1D, but also exhibit a dose response effect for BDNF. The
      intensity-dependent findings may aid in designing exercise prescriptions for
      maintaining or improving neurological health in T1D, but both types of exercise
      can be implemented.

PMID- 26212246
TI  - Aerobic Fitness for Young Athletes: Combining Game-based and High-intensity
      Interval Training.
AB  - This study compared the effect of game-based training (GT) vs. a mix of game
      based training and high-intensity interval training (MT) on physical performance
      characteristics. 26 young athletes (13.9+/-0.3 years) were assigned to either GT
      (n=13) or MT (n=13) for 6 weeks. Game-based training consisted of 2*8-11 min 3
      vs. 3 'bucketball' SSGs separated by 3 min of passive rest twice per week, while
      MT consisted of one SSGs session and one high-intensity session of 15 s runs at
      90-95% of the speed reached at the end of the 30-15 intermittent fitness test
      (VIFT) interspersed with 15 s passive recovery. Peak oxygen uptake (V O2peak),
      VIFT, jump height, and speed were assessed pre- and post-training. Following
      training, V O2peak (5.5+/-3.3%; ES=large) improved after MT, whereas VIFT
      improved after MT (6.6+/-3.2%; ES, large) and GT (4.2+/-5.5%, ES=small). 5-m
      sprint improved after GT (ES=small), while 20 m sprint and jump height were
      unchanged. In conclusion, while MT and GT were both effective at increasing
      performance parameters, greater effects were seen following MT. Therefore, MT
      should be considered as the preferred training method for improving aerobic power
      in young athletes. 

PMID- 26212247
TI  - Training-induced Increase in Bone Mineral Density between Growing Male and Female
      Rats.
AB  - The purpose of this study was to determine the existence of sex differences in
      the resistance training-induced elevation in bone mineral density (BMD) and bone
      strength (Fmax) during the growth period in rats. 16 male (M) and 16 female (F)
      rats (approx. 8 weeks old) were randomly divided into sedentary control (MC=8,
      FC=8), and resistance-trained (RT) groups (M-RT=8, F-RT=8). The RT groups were
      conditioned to climb a vertical ladder 4 consecutive times (per exercise session)
      with weights attached to their tail 3 days per week for a total of 6 weeks. After
      6 weeks, there were no interaction effects (sex*exercise). The main effect of sex
      indicated no difference in tibial BMD (in g/cm(2)) for males (0.226+/-0.005)
      compared to females (0.221+/-0.004). However, Fmax (in Newtons) was significantly
      greater for males (131.3+/-5.3) compared to females (89.9+/-3.0). The main effect
      of exercise indicated that tibial BMD and Fmax were significantly greater for RT
      groups (0.234+/-0.004 g/cm(2) and 120.9+/-7.4 Newtons) compared to controls
      (0.212+/-0.003 g/cm(2) and 100.3+/-5.1 Newtons). The results indicate that during
      growth, there were no sex differences in the training-induced elevation in BMD
      and bone mechanical properties.

PMID- 26212248
TI  - Talent in Female Gymnastics: a Survival Analysis Based upon Performance
      Characteristics.
AB  - This study investigated the link between the anthropometric, physical and motor
      characteristics assessed during talent identification and dropout in young female
      gymnasts. 3 cohorts of female gymnasts (n=243; 6-9 years) completed a test
      battery for talent identification. Performance-levels were monitored over 5 years
      of competition. Kaplan-Meier and Cox Proportional Hazards analyses were conducted
      to determine the survival rate and the characteristics that influence dropout
      respectively. Kaplan-Meier analysis indicated that only 18% of the female
      gymnasts that passed the baseline talent identification test survived at the
      highest competition level 5 years later. The Cox Proportional Hazards Model
      indicated that gymnasts with a score in the best quartile for a specific
      characteristic significantly increased chances of survival by 45-129%. These
      characteristics being: basic motor skills (129%), shoulder strength (96%), leg
      strength (53%) and 3 gross motor coordination items (45-73%). These results
      suggest that tests batteries commonly used for talent identification in young
      female gymnasts may also provide valuable insights into future dropout.
      Therefore, multidimensional test batteries deserve a prominent place in the
      selection process. The individual test results should encourage trainers to
      invest in an early development of basic physical and motor characteristics to
      prevent attrition. 

PMID- 26212249
TI  - Influence of Ergometer Design on Physiological Responses during Rowing.
AB  - The aim of this study was to compare the physiological responses and rowing
      efficiency on 2 different rowing ergometers: stationary vs. dynamic ergometers
      manufactured by Concept2. 11 oarswomen and oarsmen rowed 4 min at 60% and 70% of
      peak power output on both ergometers (randomized order). Power output, stroke
      rate, heart rate, oxygen uptake, carbon dioxide production, lactate accumulation
      and rating of perceived exertion were recorded at each stage on the 2 ergometers.
      Gross and net efficiencies were computed. Exercise intensity was associated with
      increases in all parameters. Rowing on dynamic ergometer was associated with
      higher heart rate, oxygen uptake, carbon dioxide production and stroke rate,
      concomitantly to lower blood lactate accumulation but also to lower gross and net
      efficiencies. The present study showed that rowing efficiency and blood lactate
      accumulation were lower on the Concept2 dynamic ergometer than on its stationary
      counterpart. If the use of the Concept2 dynamic ergometer may provide some
      advantages (reduced risk of injuries), its utilization requires a specific
      evaluation of physiological responses during an incremental exercise for an
      adapted management of training. 

PMID- 26212250
TI  - VEGF-Mediated Induction of PRD1-BF1/Blimp1 Expression Sensitizes Tumor
      Vasculature to Oncolytic Virus Infection.
AB  - Oncolytic viruses designed to attack malignant cells can in addition infect and
      destroy tumor vascular endothelial cells. We show here that this expanded tropism
      of oncolytic vaccinia virus to the endothelial compartment is a consequence of
      VEGF-mediated suppression of the intrinsic antiviral response. VEGF/VEGFR2
      signaling through Erk1/2 and Stat3 leads to upregulation, nuclear localization,
      and activation of the transcription repressor PRD1-BF1/Blimp1. PRD1-BF1 does not
      contribute to the mitogenic effects of VEGF, but directly represses genes
      involved in type I interferon (IFN)-mediated antiviral signaling. In vivo
      suppression of VEGF signaling diminishes PRD1-BF1/Blimp1 expression in tumor
      vasculature and inhibits intravenously administered oncolytic vaccinia delivery
      to and consequent spread within the tumor.

PMID- 26212251
TI  - Idiopathic interstitial pneumonias with connective tissue diseases features: A
      review.
AB  - A systematic approach is recommended to search for clinical and biological
      features of connective tissue disease (CTD) in any patient with interstitial lung
      disease (ILD). In the diagnostic approach to ILD, a diagnosis of CTD should be
      considered particularly in women and subjects younger than 50 years, and in those
      with an imaging and/or pathological pattern of non-specific interstitial
      pneumonia. However, the diagnosis of CTD may be difficult when ILD is the
      presenting or the dominant manifestation of CTD. A proportion of patients with
      ILD present symptoms that belong to the spectrum of CTD and/or biological
      autoimmune features, but do not fulfil diagnostic criteria for a given CTD. Some
      imaging and histopathological patterns may also suggest the presence of an
      underlying CTD. Although studies published to date used heterogeneous definitions
      and terminology for this condition, evidence is accumulating that even limited
      CTD features are relevant regarding symptoms, imaging features, pathological
      pattern and possibly evolution to overt CTD, whereas the impact on prognosis
      needs confirmation. Conversely, autoantibodies alone do not seem to impact the
      prognosis or management in patients with otherwise typical idiopathic pulmonary
      fibrosis and no extra-pulmonary manifestation. A collective international
      multidisciplinary effort has proposed a uniform definition and criteria for
      'interstitial pneumonia with autoimmune features', a condition characterized by
      limited CTD features occurring in the setting of ILD, with the aim of fostering
      future clinical studies. Referral of ILD patients suspect to have CTD to a
      rheumatologist and possibly multidisciplinary discussion may contribute to a
      better management. 

PMID- 26212253
TI  - Structure Characterization and Properties of Metal-Surfactant Complexes Dispersed
      in Organic Solvents.
AB  - This work describes the synthesis and characterization of metal-surfactant
      complexes. Dioctyl sulfosuccinate and dodecylbenzenesulfonate are associated with
      multivalent aluminum, iron, and vanadium ions using an ion exchange reaction. The
      metal complexes are dispersible in various organic solvents. In solvents with low
      polarity, the complexes form "inverse" macromolecular structures with multiple
      metal ions. In contrast, in alcohols, the complex size is reduced, showing a more
      disperse conformation. The metal and surfactant ions are still strongly bonded to
      each other in all the solvents probed. Small-angle X-ray and neutron scattering
      (SAXS and SANS) are used to characterize the structures. Simultaneous fitting of
      neutron and X-ray scattering spectra is performed in order to obtain an accurate
      description of the system. Scattering results are also validated by performing
      molecular dynamics (MD) simulations. The conductive and electrochemical
      properties of the complexes in solution are also evaluated. The dispersion of
      metal-organic complexes significantly increases electric conductivity, and some
      metal ions in the core of the complexes are shown to be electrochemically active
      in apolar solvents. 

PMID- 26212252
TI  - Occupational contact urticaria: lessons from the French National Network for
      Occupational Disease Vigilance and Prevention (RNV3P).
AB  - BACKGROUND: Occupational contact urticaria (OCU) is an occupational contact
      dermatitis that can cause serious health consequences and disability at work.
      OBJECTIVES: To describe OCU and its temporal trends by the main causal agents and
      activity sectors in a nationwide scheme in France. METHODS: Using data from the
      French National Network for Occupational Disease Vigilance and Prevention
      (RNV3P), we described OCU reported during the period 2001-10 and analysed the
      temporal trends of OCU and OCU attributed to the most frequent agents over the
      study period. Trends analyses were supported by reporting odds ratios using a
      logistic regression model with reference to 2001, or with time as a continuous
      variable. RESULTS: During the study period, 251 cases of OCU were reported in
      RNV3P, half of which were due to natural rubber latex, in particular in the
      health and social work activity sector (HSW). The number of these cases declined
      significantly over the study period (19% per year), and particularly after 2006.
      Conversely, the other causes of OCU did not decrease. CONCLUSIONS: Using
      surveillance data from a French national network, this study has found that there
      was a significant decline in OCU due to natural rubber latex, particularly in the
      HSW, when powdered latex gloves were banned from French hospitals. Our results
      show the effectiveness of this preventive measure, and suggest that this practice
      should be extended to other sectors.

PMID- 26212254
TI  - The potential of cholesteryl ester transfer protein as a therapeutic target.
AB  - INTRODUCTION: Over recent decades, attempts to ascertain the pro-atherogenic
      nature of plasma cholesteryl ester transfer protein (CETP) and to establish the
      relevance of its pharmacological blockade as a promising high density
      lipoproteins-raising and anti-atherogenic therapy have been disappointing. AREAS
      COVERED: The current review focuses on CETP as a multifaceted protein, on genetic
      variations at the CETP gene and on their possible consequences for cardiovascular
      risk in human populations. Specific attention is given to physiological
      modulation of endogenous CETP activity by the apoC1 inhibitor. Finally, the
      rationale behind the need for selection of patients to treat is discussed in the
      light of recent studies. EXPERT OPINION: At this stage one can only speculate on
      the clinical outcome of pharmacological CETP inhibitors in high-risk populations,
      but recent advances give cause to adjust the expectations from now on. The CETP
      effect is probably largely influenced by the overall metabolic state, and whether
      CETP blockade may be relevant or not in promoting cholesterol disposal is still
      questioned. The possible need for a careful stratification of patients to treat
      with CETP inhibitors is outlined. Finally, manipulation of CETP activity should
      be considered with caution in the context of sepsis and infectious diseases.

PMID- 26212255
TI  - Determination of sulphachloropyrazine-diaveridine residues by high performance
      liquid chromatography in broiler edible tissues.
AB  - Diaveridine (DVD) is used in combination with sulphachloropyrazine (SPZ) as an
      effective antibacterial agent and antiprotozoal agent, respectively, in humans
      and animals. To gain a better understanding of the metabolism of SPZ and DVD in
      the food-producing animals, a high performance liquid chromatography (HPLC)
      method to determine and quantify sulphachloropyrazine (SPZ) and diaveridine (DVD)
      suspension residues from broilers is reported. Thirty healthy chickens were
      orally administered with sulphachloropyrazine-diaveridine (SPZ-DVD) suspension in
      water of 300 mg/l (SPZ) per day for seven successive days. Six chickens per day
      were slaughtered at 0, 1, 3, 5 and 7 days after the last administration. This
      procedure permitted SPZ and DVD to be separated from muscle tissue, liver,
      kidneys and skin with fat after extraction with acetonitrile and acetone under
      slightly acidic conditions. From the detected residuals in different tissues, we
      found that SPZ was quickly eliminated in liver and muscle, and slowly eliminated
      in kidney and skin with fat. DVD was quickly eliminated in liver and slowly
      eliminated in kidney. The withdrawal period of SPZ was 3.26, 3.72, 4.39 and 5.43
      days in muscle, liver, kidney and skin with fat, respectively. The withdrawal
      period of DVD was 4.77, 4.94, 6.74 and 4.58 days in muscle, liver, kidney and
      skin with fat, respectively. Therefore, the suggested withdrawal period for SPZ
      DVD suspension should be 7 days after dosing for seven successive days. 

PMID- 26212256
TI  - Ultrasound biomicroscopic findings of the iridocorneal angle in live healthy and
      glaucomatous dogs.
AB  - By using ultrasound biomicroscopy (UBM), the cross-sectional structures of the
      entire iridocorneal angle (ICA) which are unable to assess with gonioscopic
      examination were evaluated objectively and quantitatively in live healthy and
      glaucomatous dogs. The ICAs of normotensive eyes in healthy dogs with normal open
      angle (NOR), a predisposition to primary closed angle glaucoma (PCAG) (PREDIS)
      and suffering from unilateral PCAG (UNI), as well as the ICAs of hypertensive
      eyes with acute and chronic PCAG (ACG and CRG), were assessed. The opening of the
      ciliary cleft in PREDIS was smaller than that in NOR. In UNI, the opening and
      area of the ciliary cleft were significantly decreased compared with those of NOR
      and PREDIS. ACG had widespread structural abnormalities including marked decrease
      in the ciliary cleft and scleral venous plexus, and a thinner sclera than those
      in normotensive eyes, whereas the ICA collapsed in CRG with the thinnest sclera.
      Medical therapy-responsive glaucomatous cases had wider ciliary cleft and scleral
      venous plexus than unresponsive ones. These findings suggest that the ciliary
      cleft and scleral venous plexus of the ICA are key structures contributing to not
      only the pathophysiology of canine glaucoma but also the responsiveness to
      medical therapy in glaucomatous eyes, and cross-sectional entire structures of
      the ICA should be evaluated quantitatively with UBM when diagnosing and managing
      canine glaucoma. 

PMID- 26212257
TI  - Resveratrol and curcumin synergistically induces apoptosis in cigarette smoke
      condensate transformed breast epithelial cells through a p21(Waf1/Cip1) mediated
      inhibition of Hh-Gli signaling.
AB  - Combination therapy using two or more small molecule inhibitors of aberrant
      signaling cascade in aggressive breast cancers is a promising therapeutic
      strategy over traditional monotherapeutic approaches. Here, we have studied the
      synergistic mechanism of resveratrol and curcumin induced apoptosis using in
      vitro (cigarette smoke condensate mediated transformed breast epithelial cell,
      MCF-10A-Tr) and in vivo (tumor xenograft mice) model system. Resveratrol exposure
      increased the intracellular uptake of curcumin in a dose dependent manner and
      caused apoptosis in MCF-10A-Tr cells. Approximately, ten fold lower IC50 value
      was noted in cells treated with the combination of resveratrol (3MUM) and
      curcumin (3MUM) in comparison to 30MUM of resveratrol or curcumin alone.
      Resveratrol+curcumin combination caused apoptosis by increasing Bax/Bcl-xL ratio,
      Cytochrome C release, cleaved product of PARP and caspase 3 in cells.
      Interestingly, this combination unaltered the protein expressions of WNT-TCF and
      Notch signaling components, beta-catenin and cleaved notch-1 val1744,
      respectively. Furthermore, the combination also significantly decreased the
      intermediates of Hedgehog-Gli cascade including SMO, SHH, Gli-1, c-MYC, Cyclin
      D1, etc. and increased the level of p21(Waf/Cip1) in vitro and in vivo. A
      significant reduction of Gli- promoter activity was noted in combinational drug
      treated cells in comparison to individual drug treatment. Un-alteration of the
      expressions of the above proteins and Gli1 promoter activity in p21(Waf/Cip1)
      knockout cells suggests this combination caused apoptosis through p21(Waf/Cip1).
      Thus, our findings revealed resveratrol and curcumin synergistically caused
      apoptosis in cigarette smoke induced breast cancer cells through p2(Waf/Cip1)
      mediated inhibition of Hedgehog-Gli cascade. 

PMID- 26212259
TI  - Promoting weight loss methods in parenting magazines: Implications for women.
AB  - Weight gain before and after pregnancy is important for women's health. The
      purpose of this study was to assess articles and advertisements related to weight
      loss in three widely read parenting magazines, "Parenting School Years,"
      "Parenting Early Years," and "Parenting," which have an estimated combined
      readership of approximately 24 million (mainly women readers). Almost a quarter
      (23.7%, n = 32) of the 135 magazine issues over a four year period included at
      least one feature article on weight loss. A variety of topics were covered in the
      featured articles, with the most frequent topics being on losing weight to please
      yourself (25.2%), healthy ways to lose weight (21.1%), and how to keep the weight
      off (14.7%). Less than half (45.9%) of the articles displayed author credentials,
      such as their degree, qualifications, or expertise. A fifth (20.0%, n = 27) of
      the magazines included at least one prominent advertisement for weight loss
      products. Almost half (46.9%) of the weight loss advertisements were for weight
      loss programs followed by weight loss food products (25.0%), weight loss aids
      (21.9%), and only 6.2% of the advertisements for weight loss were on fitness.
      Parenting magazines should advocate for healthy weight loss, including lifestyle
      changes for sustained health. 

PMID- 26212258
TI  - Vitamin K3 (menadione) redox cycling inhibits cytochrome P450-mediated metabolism
      and inhibits parathion intoxication.
AB  - Parathion, a widely used organophosphate insecticide, is considered a high
      priority chemical threat. Parathion toxicity is dependent on its metabolism by
      the cytochrome P450 system to paraoxon (diethyl 4-nitrophenyl phosphate), a
      cytotoxic metabolite. As an effective inhibitor of cholinesterases, paraoxon
      causes the accumulation of acetylcholine in synapses and overstimulation of
      nicotinic and muscarinic cholinergic receptors, leading to characteristic signs
      of organophosphate poisoning. Inhibition of parathion metabolism to paraoxon
      represents a potential approach to counter parathion toxicity. Herein, we
      demonstrate that menadione (methyl-1,4-naphthoquinone, vitamin K3) is a potent
      inhibitor of cytochrome P450-mediated metabolism of parathion. Menadione is
      active in redox cycling, a reaction mediated by NADPH-cytochrome P450 reductase
      that preferentially uses electrons from NADPH at the expense of their supply to
      the P450s. Using human recombinant CYP 1A2, 2B6, 3A4 and human liver microsomes,
      menadione was found to inhibit the formation of paraoxon from parathion.
      Administration of menadione bisulfite (40mg/kg, ip) to rats also reduced
      parathion-induced inhibition of brain cholinesterase activity, as well as
      parathion-induced tremors and the progression of other signs and symptoms of
      parathion poisoning. These data suggest that redox cycling compounds, such as
      menadione, have the potential to effectively mitigate the toxicity of
      organophosphorus pesticides including parathion which require cytochrome P450
      mediated activation. 

PMID- 26212260
TI  - A cost-effectiveness analysis of opioid substitution therapy upon prison release
      in reducing mortality among people with a history of opioid dependence.
AB  - AIM: Although opioid substitution therapy (OST) immediately after prison release
      reduces mortality, the cost-effectiveness of treatment has not been examined.
      Therefore, we undertook a cost-effectiveness analysis of OST treatment upon
      prison release and the prevention of death in the first 6 months post-release.
      DESIGN: Population-based, retrospective data linkage study using records of OST
      entrants (1985-2010), charges and court appearances (1993-2011), prison episodes
      (2000-11) and death notifications (1985-2011). SETTING: New South Wales,
      Australia. PARTICIPANTS: A cohort of 16,073 people with a history of opioid
      dependence released from prison for the first time between 1 January 2000 and 30
      June 2011. INTERVENTION: OST treatment compared to no OST treatment at prison
      release. MEASUREMENTS: Mortality and costs (treatment, criminal justice system
      court, penalties, prison-and the social costs of crime) were evaluated at 6
      months post-release. Analyses included propensity score matching, bootstrapping
      and regression. FINDINGS: A total of 13,468 individuals were matched (6734 in
      each group). Twenty (0.3%) people released onto OST died, compared with 46 people
      (0.7%) not released onto OST. The final average costs were lower for the group
      that received OST post-release ($7206 versus $14,356). The incremental cost
      effectiveness ratio showed that OST post-release was dominant, incurring lower
      costs and saving more lives. The probability that OST post-release is cost
      effective per life-year saved is 96.7% at a willingness to pay of $500.
      CONCLUSION: Opioid substitution treatment (compared with no such treatment),
      given on release from prison to people with a history of opioid dependence, is
      cost-effective in reducing mortality in the first 6 months of release.

PMID- 26212261
TI  - Impairment of Liver Glycogen Storage in the db/db Animal Model of Type 2
      Diabetes: A Potential Target for Future Therapeutics?
AB  - After the discovery of the db gene in 1966, it was determined that a blood-borne
      satiety factor was produced excessively, but was not responded to, in db/db mice.
      This model for type 2 diabetes is widely used since it phenocopies human disease
      and its co-morbidities including obesity, progressive deterioration in glucose
      tolerance, hypertension and hyperlipidaemia. Db/db mice, unlike their non
      diabetic controls, have consistently elevated levels of liver glycogen, most
      likely due to hyperphagia. In transmission electron micrographs, liver glycogen
      usually shows a composite cauliflower-like morphology of large "alpha particles"
      (with a wide range of sizes) made up of smaller "beta particles" bound together.
      New studies have explored the size distribution of liver glycogen molecules and
      found that alpha particles in db/db mice are more chemically fragile than those
      in healthy mice, and can readily break apart to smaller beta particles. There is
      evidence that smaller glycogen particles have a higher association with glycogen
      phosphorylase, a key enzyme involved in glycogen degradation, as well as being
      degraded more rapidly in vitro; therefore the inability to form stable large
      glycogen alpha particles is predicted to result in a faster, less controlled
      degradation into glucose. The implications of this for glycaemic control remain
      to be fully elucidated. However, "rescuing" the more fragile diabetic glycogen to
      decrease hepatic glucose output in type 2 diabetes, may provide a potential
      therapeutic target which is the subject of this review. 

PMID- 26212262
TI  - Phospholipase A2 Isoforms as Novel Targets for Prevention and Treatment of
      Inflammatory and Oncologic Diseases.
AB  - Phospholipase A2s (PLA2s) are group of enzymes, which cleave phospholipids
      specifically at sn-2 position to liberate free fatty acid, mostly arachidonic
      acid (AA) and lysophospholipids (LPLs). Inhibition of PLA2 prevents the
      liberation of AA and LPLs. Hence, researchers have been considering PLA2s could
      be a better therapeutic target than the downstream enzymes cyclooxygense and
      lipoxygenase. Several isoforms of PLA2s exist; they are mainly divided into
      secretory PLA2s (sPLA2), cytosolic PLA2s (cPLA2), and calcium independent PLA2s
      (iPLA2), platelet activating factor- acyl hydrolase (PAF-AH), lysosomal PLA2
      (LPLA2), adipose-specific PLA2 (Ad- PLA). Each isoform of PLA2s is different in
      its chemical structure and physiological functions. sPLA2s (Groups IIA, V and X)
      are well characterized as proinflammatory mediating enzymes but their role in
      cancer is controversial. Groups IVA, IVB and IVC cPLA2s are present in humans but
      only Group IVA cPLA2 plays key role in pathophysiology of various cancers and
      inflammation. The role of iPLA2 in inflammation and cancer is limited.
      Lipoprotein associated PLA2 (Group VIIA PLA2), a PAF-AH isoform, has key role in
      atherosclerosis. Several isoform specific PLA2 inhibitors have been developed and
      some of the PLA2s inhibitors are currently under clinical trials for various
      inflammatory and oncologic diseases. This review focuses on the recent
      experimental evidences to support the notion that PLA2s are causally implicated
      in the pathobiology of cancer and inflammatory related disorders and discuss the
      potential utility of isoform specific PLA2 inhibitors as preventive and/or
      therapeutic agents.

PMID- 26212264
TI  - HDL as a Target for Glycemic Control.
AB  - HDL has long been known for its role in reverse cholesterol transport, thought in
      part to explain the well-recognized links between low levels of HDL-C and
      cardiovascular disease. The past decade has seen increasing evidence from
      epidemiological, basic science and early human intervention studies that HDL
      biology is more complex and may influence the onset and progression of type 2
      diabetes. Research has identified multiple potential pathways by which higher HDL
      particle concentrations or functional improvements may ameliorate the development
      and progression of the disease. These include promotion of insulin secretion and
      pancreatic islet beta-cell survival, promotion of peripheral glucose uptake, and
      suppression of inflammation. The relationships between HDL-C levels, commonly
      used in clinical practice, and HDL particle number, size and various HDL
      functions is complex, and is intimately linked with triglyceride metabolism. The
      complexity of these relationships is amplified in diabetes, which negatively
      impacts multiple aspects of lipoprotein biology. This article reviews the
      rationale for, and potential of, HDL-based anti-diabetic pharmacotherapy, with an
      emphasis on the particular challenges posed by diabetes-related HDL dysfunction,
      and on the difficulties of selecting appropriate targets and HDL-related
      biomarkers for research and for clinical practice. We discuss aspects of HDL
      metabolism that are known to be altered in type 2 diabetes, potentially useful
      measures of HDL-targeted therapy in diabetes, and review early intervention
      studies in humans. These areas provide a firm foundation for further research and
      knowledge expansion in this intriguing area of human health and disease.

PMID- 26212263
TI  - Targeting the Eph System with Peptides and Peptide Conjugates.
AB  - Eph receptor tyrosine kinases and ephrin ligands constitute an important cell
      communication system that controls development, tissue homeostasis and many
      pathological processes. Various Eph receptors/ephrins are present in essentially
      all cell types and their expression is often dysregulated by injury and disease.
      Thus, the 14 Eph receptors are attracting increasing attention as a major class
      of potential drug targets. In particular, agents that bind to the extracellular
      ephrin-binding pocket of these receptors show promise for medical applications.
      This pocket comprises a broad and shallow groove surrounded by several flexible
      loops, which makes peptides particularly suitable to target it with high affinity
      and selectivity. Accordingly, a number of peptides that bind to Eph receptors
      with micromolar affinity have been identified using phage display and other
      approaches. These peptides are generally antagonists that inhibit ephrin binding
      and Eph receptor/ ephrin signaling, but some are agonists mimicking ephrin
      induced Eph receptor activation. Importantly, some of the peptides are
      exquisitely selective for single Eph receptors. Most identified peptides are
      linear, but recently the considerable advantages of cyclic scaffolds have been
      recognized, particularly in light of potential optimization towards drug leads.
      To date, peptide improvements have yielded derivatives with low nanomolar Eph
      receptor binding affinity, high resistance to plasma proteases and/or long in
      vivo half-life, exemplifying the merits of peptides for Eph receptor targeting.
      Besides their modulation of Eph receptor/ephrin function, peptides can also serve
      to deliver conjugated imaging and therapeutic agents or various types of
      nanoparticles to tumors and other diseased tissues presenting target Eph
      receptors. 

PMID- 26212266
TI  - Virtual Screening for the Development of Dual-Inhibitors Targeting Topoisomerase
      IB and Tyrosyl-DNA Phosphodiesterase 1.
AB  - Human topoisomerase IB is an important target in cancer therapy and drugs
      selectively stabilizing the topoisomerase IB-DNA covalent complex are in clinical
      use for several cancer types. Tyrosyl- DNA phosphodiesterase 1 is involved in the
      DNA repair resolving the topoisomerase IB-DNA covalent complex that is extremely
      dangerous for the survival of the cells since it produces an irreversible DNA
      damage. Given the close biological relationship between these two enzymes, the
      development of synergistic inhibitors, called dual-inhibitors, is an important
      challenge in cancer therapy and computer-aided drug design may help in the
      identification of the best compounds. In this review, an overview of the
      compounds inhibiting one of the two enzymes or acting as dual inhibitors is
      provided. Moreover, the general procedures of the virtual screening approach,
      providing a description of two widely used opensource programs, namely AutoDock4
      and AutoDock Vina, are described. Finally, an application of the two programs on
      a selected number of dual inhibitors for tyrosyl-DNA phosphodiesterase 1 and
      topoisomerase IB and their performance is briefly discussed.

PMID- 26212265
TI  - ALDH2---The Genetic Polymorphism and Enzymatic Activity Regulation: Their
      Epidemiologic and Clinical Implications.
AB  - BACKGROUND: The human aldehyde dehydrogenase 2 (ALDH2) is the most effective
      enzyme in the detoxification of alcohol metabolite acetaldehyde. The ALDH2*2
      mutation is caused by a single nucleotide substitution which results in a nearly
      inactive form of ALDH2 enzyme. The ALDH2 genotype has been used as a surrogate of
      alcohol to get causal inferences of alcohol in related diseases implementing
      Mendelian randomization approach. In addition, ALDH2 enzyme has significant
      effect on different diseases, indicating the potential therapeutic value of ALDH2
      regulators including both activators like Alda-1 and inhibitors such as daidzin
      and daidzein. OBJECTIVE: In this review, we aim to systematically discuss the
      implications of ALDH2 genotype and ALDH2 enzyme regulators, highlighting their
      epidemiological and clinical importance, respectively. CONCLUSION: ALDH2
      polymorphism is shown to be a genetic instrument for alcohol use in Mendelian
      randomization analysis. ALDH2 regulators exhibit potential therapeutic value as
      the important roles of ALDH2 in various diseases. Both the genetic polymorphism
      and enzyme activity regulation of ALDH2 are of great importance to their
      epidemiologic and clinical applications.

PMID- 26212267
TI  - Tapping into Mitochondria to Find Novel Targets for Diabetes Complications.
AB  - Mitochondria produce the majority of cellular energy via the "slow burn" of
      substrates such as glucose, free fatty acids and ketones. In diabetes, altered
      mitochondrial energetics and substrate utilisation may explain, in part, an
      organ's susceptibility to complications. This is particularly evident at sites
      such as the kidney, heart, neurons and retina, which have high energy demands and
      oxygen consumption rates to meet functional requirements. Within this review we
      highlight the recent research implicating mitochondrial dysfunction, with
      particular focus on the contribution of mitochondrial reactive oxygen species, on
      the development and progression of diabetes complications. Finally, we discuss
      the current strategies which are being assessed to combat mitochondrial
      dysfunction in diabetes complications.

PMID- 26212268
TI  - A qualitative study exploring how school and community environments shape the
      food choices of adolescents with overweight/obesity.
AB  - This study explored perceived barriers and facilitators to healthful eating in
      schools and communities among overweight teens who completed an E-health
      intervention. Twenty-two teens were recruited to a photovoice study and asked to
      take pictures of things that made it easier or harder to make healthful food
      choices at school and in their community. Digital photographs were reviewed using
      semi-structured interviews. Transcribed audio-recordings were analyzed using
      constant comparative analysis. Similar themes emerged from the school and
      community environments with food/beverage availability emerging most frequently,
      followed by peer influence, accessibility/convenience, price, classroom
      practices, marketing and online influences. Teens described an obesity-promoting
      environment and perceived very limited healthful options. Policy-driven
      environmental changes as well as strategies that help teens navigate food choices
      in their schools and communities are needed to support healthful eating. 

PMID- 26212269
TI  - "Because we missed the way that we eat at the middle of the day:" Dietary
      acculturation and food routines among Dominican women.
AB  - Better understanding of dietary change mechanisms among growing immigrant
      populations is needed in light of increased risk for diet-related chronic health
      conditions and inconsistent associations between acculturation and diet. This
      grounded theory research aimed to understand the lived experiences of
      interactions between food culture and social, economic, and physical environments
      in an immigrating population, Dominican women living in the Dominican Republic
      and New York City. Twenty-nine Dominican women participated in qualitative
      interviews about food and eating behaviors, life course experiences, and
      environments. Daily food and eating routines, framed by shopping for, preparation
      of, and consumption of 'la comida' or the main meal, emerged as dominant themes
      reflecting differences in women's economic, social, and physical environments.
      Routines were shaped by employment, household characteristics, and the food
      environment. Participating women attributed weight gain to changes in their food
      routines following immigration. The construction, disruption, and reconstruction
      of food and eating routines in response to differing economic, social, and
      physical environments in the sending and the receiving cultures provided new
      insights into the relationship between structural and cultural contexts of food
      and eating in an immigrant population. A food routines framework provides new
      insights into behavioral and weight changes with immigration. 

PMID- 26212270
TI  - Gating of attention towards food stimuli in binge eating disorder.
AB  - Cognitive models of eating disorders propose that attentional biases for disorder
      relevant stimuli contribute to eating disorder pathology. Empirical evidence of a
      contribution of attentional biases for binge eating disorder (BED) is still
      scarce. The aim of the present study was to assess attention engagement towards,
      and disengagement from, food stimuli in overweight females with BED (n = 25) and
      a group of overweight and obese women without BED (OW; n = 30). Participants
      completed a rapid serial visual presentation (RSVP) paradigm with food and
      neutral words as target stimuli. This task can be used to decompose an
      attentional bias for food stimuli into its stimulus engagement and stimulus
      disengagement components. Findings indicate that facilitated stimulus engagement
      for food stimuli over neutral stimuli was more pronounced in the BED group
      compared to the OW group. Conversely, there were no substantial disengagement
      effects in either group. Thereby, results support the idea that early attentional
      processes are biased in BED.

PMID- 26212271
TI  - Outpatient parenteral antimicrobial therapy (OPAT) in patients with cystic
      fibrosis.
AB  - BACKGROUND: To determine complications during outpatient parenteral antimicrobial
      therapy (OPAT) administrated through a peripheral venous line, PICC-line or PORT
      A-CATH (PAC). METHODS: Catheter related complications in patients with cystic
      fibrosis during OPAT were identified through a retrospective review of patient
      files supplemented by an interview. RESULTS: In 64 treatment episodes with a
      peripheral venous line, 51 (79.7 %) used bolus injection and 13 (20.3 %) used
      infusion pump. 27 out of 51 (53.0 %) bolus injection episodes experienced
      complications, which required removal. None were observed for infusion pump
      treatments. The infectious complications requiring removal of peripheral venous
      line were 9 out of 23 (39.1 %) for the PICC line and 11 out of 26 (42.3 %) for
      the PAC. No anaphylaxis was observed during the OPAT treatments. CONCLUSIONS: Our
      data indicate that using an infusion pump to administer the antibiotic treatment
      minimized peripheral venous line complications. The frequency of complications
      leading to removal of the catheter is about the same for PICC-lines and PACs, but
      the average life-time of the latter is much longer. Allergic reactions are not a
      major problem.

PMID- 26212272
TI  - A platform for the structural characterization of glycans enzymatically released
      from glycosphingolipids extracted from tissue and cells.
AB  - RATIONALE: Glycosphingolipids (GSLs) constitute a highly diverse class of glyco
      conjugates which are involved in many aspects of cell membrane function and
      disease. The isolation, detection and structural characterization of the
      carbohydrate (glycan) component of GSLs are particularly challenging given their
      structural heterogeneity and thus rely on the development of sensitive,
      analytical technologies. METHODS: Neutral and acidic GSL standards were
      immobilized onto polyvinylidene difluoride (PVDF) membranes and glycans were
      enzymatically released using endoglycoceramidase II (EGCase II), separated by
      porous graphitized carbon (PGC) liquid chromatography and structurally
      characterized by negative ion mode electrospray ionization tandem mass
      spectrometry (PGC-LC/ESI-MS/MS). This approach was then employed for GSLs
      isolated from 100 mg of serous and endometrioid cancer tissue and from cell line
      (10(7) cells) samples. RESULTS: Glycans were released from GSL standards
      comprising of ganglio-, asialo-ganglio- and the relatively resistant globo-series
      glycans, using as little as 1 mU of enzyme and 2 ug of GSL. The platform of
      analysis was then applied to GSLs isolated from tissue and cell line samples and
      the released isomeric and isobaric glycan structures were chromatographically
      resolved on PGC and characterized by comparison with the MS(2) fragment ion
      spectra of the glycan standards and by application of known structural MS(2)
      fragment ions. This approach identified several (neo-)lacto-, globo- and ganglio
      series glycans and facilitated the discrimination of isomeric structures
      containing Lewis A, H type 1 and type 2 blood group antigens and sialyl
      tetraosylceramides. CONCLUSION: We describe a relatively simple, detergent-free,
      enzymatic release of glycans from PVDF-immobilized GSLs, followed by the detailed
      structural analysis afforded by PGC-LC-ESI-MS/MS, to offer a versatile method for
      the analysis of tumour and cell-derived GSL-glycans. The method uses the
      potential of MS(2) fragmentation in negative ion ESI mode to characterize, in
      detail, the biologically relevant glycan structures derived from GSLs.

PMID- 26212273
TI  - Analytical aspects of measuring (2)H/(1)H and (18)O/(16)O ratios in urine from
      doubly labelled water studies by high-temperature conversion elemental analyser
      isotope-ratio mass spectrometry.
AB  - RATIONALE: Total Body Water (TBW) and Total Energy Expenditure (TEE) are
      routinely measured in free-living conditions by the (2)H2(18)O method. Isotope
      eliminations can be measured from spot urine samples by HTC-EA IRMS, but only
      after cumbersome cryogenic distillation to extract water. Distillation may,
      however, be replaced by charcoal treatment and filtration. This study tested (1)
      the effect of sample treatments (filtration versus distillation) on the isotope
      ratios, (2) the effect of different ways of normalization that respect or not the
      principle of identical treatment of the sample and references, and (3) the impact
      on the biological outcomes. METHODS: Two filters (PES membrane; 10 kDa) accepting
      volumes of urine samples (V500: 0.5 mL versus V6: 3.0 mL) were tested. In-house
      water standards and in-house urine standards were prepared and normalized against
      the international scale to calibrate the urine samples. The delta(2)H and
      delta(18)O values from water in the urine were measured by HTC-EA IRMS. RESULTS:
      Filtered urine normalized with water standards showed a bias in the delta(2)H
      values that was corrected when calibration was performed with urine standards. At
      a delta(2)H value of 1101.40/00, the accuracy increased from -11.9 to -0.2
      delta0/00 (V500) and from -3.8 to 0.4 delta0/00 (V6). The TBW errors were
      greatest with V500 and water calibration (1.20%) and lowest with V6 and urine
      calibration (0.34%; preparation-by-calibration interaction p = 0.027). For the
      delta(18)O values the accuracy of enrichments and TBW were not affected whatever
      preparations and normalization were used. The average TEE was not affected but
      the variability increased from 0.6 to 2.7% versus cryogenic distillation.
      CONCLUSIONS: Cryogenic distillation remains the gold standard for small sample
      size experiments where small changes in TEE are to be detected. Filtration offers
      an alternative for large-scale experiments. When the body composition is derived
      from (2)H2O dilution, it is strongly recommended that urine standards should be
      used to eliminate the effect of filtration.

PMID- 26212274
TI  - Analytical characterization of bioactive N-benzyl-substituted phenethylamines and
      5-methoxytryptamines.
AB  - RATIONALE: Substances based on the N-(2-methoxybenzyl)phenethylamine template
      ('NBOMe' derivatives) play an important role in medicinal research but some of
      these derivatives have also appeared as 'research chemicals' for recreational use
      which has attracted attention worldwide. A major challenge associated with newly
      emerging substances includes the lack of analytical data and the ability to
      correctly identify positional isomers. METHODS: Six N-benzylphenethylamines based
      on the 2,5-dimethoxy-4-iodophenethylamine structure ('25I') and twelve
      substituted N-benzyl-5-methoxytryptamines ('5MT') have been prepared and
      extensively characterized. Techniques used for characterization were gas
      chromatography/ion trap mass spectrometry in electron and chemical ionization
      mode, liquid chromatography/diode array detection (DAD), infrared spectroscopy,
      electrospray high mass accuracy quadrupole time-of-flight tandem mass
      spectrometry, and triple quadrupole tandem mass spectrometry. RESULTS: The
      characterization of 18 'NBOMe' compounds provided a comprehensive collection of
      chromatographic and spectral data. Four groups of three positional isomers, i.e.
      25I-NB2OMe, 25I-NB3OMe, 25I-NB4OMe, 25I-NB2B, 25I-NB3B, 25I-NB4B and their 5
      methoxytryptamine counterparts, were included and assessed for ability to obtain
      differentiation. Six meta-substituted N-benzyl derivatives of 5-methoxytryptamine
      (CF3, F, CH3, Cl, I, SCH3) were also studied. CONCLUSIONS: The implementation of
      mass spectral techniques was helpful for the differentiation between isomers, for
      example, when considering the difference in a number of ion ratios. This was
      considered beneficial in cases where chromatographic separation was only
      partially achieved under liquid chromatography (LC) conditions. The use of LC/DAD
      analysis was also found to be valuable for this particular purpose, which
      confirmed the integrative value of complementary techniques used in areas related
      to forensic toxicology.

PMID- 26212275
TI  - Transmission mode desorption atmospheric pressure photoionization.
AB  - RATIONALE: Desorption atmospheric pressure photoionization (DAPPI) is an ambient
      mass spectrometry (MS) technique that is suitable for the direct analysis of
      polar and nonpolar compounds from a variety of surfaces. Conventional DAPPI uses
      reflection geometry, but here transmission mode (TM)-DAPPI is introduced for fast
      and easy analysis of liquid samples. METHODS: Stainless steel and PEEK meshes
      were used as sampling support in TM-DAPPI. The sample was applied either in the
      form of a droplet on the mesh, or by dipping the mesh in the sample solution.
      Physical parameters affecting the ionization efficiency were optimized for TM
      DAPPI. The mesh materials were used to extract compounds from aqueous samples,
      which were then analyzed by TM-DAPPI. TM-DAPPI and conventional DAPPI were
      compared. RESULTS: In TM-DAPPI, intense signals for the analytes were achieved
      with less heating power, and lower nebulizer gas and dopant flow rates than
      optimally used in conventional DAPPI. Either due to this, or the different sample
      support material used, a much lower background and improved sensitivity compared
      to conventional DAPPI was achieved. The analytes could be extracted and
      concentrated from liquid samples on the mesh material used in TM-DAPPI, which was
      especially efficient for the nonpolar benzo[a]pyrene. This effect was utilized in
      the analysis of triacylglycerols from cow milk. CONCLUSIONS: While conventional
      DAPPI is still the method of choice for solid samples, TM-DAPPI can be utilized
      as a fast, easily automated method for analyzing liquid samples. The mesh
      materials can be utilized for extraction of low polarity compounds, such as
      steroid hormones or PAHs from dilute, aqueous solutions, followed by subsequent
      analysis by TM-DAPPI.

PMID- 26212276
TI  - Comparison of three pretreatment methods for the analysis of distributions and
      hydrogen isotopic compositions of leaf wax n-fatty acids in natural samples.
AB  - RATIONALE: The hydrogen isotopic compositions (delta(2)H values) of leaf wax n
      fatty acids (n-FAs) are widely used as powerful biomarkers in biogeochemical and
      paleoenvironmental studies. However, the use of a variety of pretreatment methods
      to isolate n-FAs from natural samples for the measurement of delta(2)H values
      potentially causes discrepancies in the measured delta(2)H values, thereby
      confounding their use as a biomarker. METHODS: We tested three typical
      pretreatment methods for the analysis of the distributions and delta(2)H values
      of n-FAs from terrestrial higher plants (Carex siderosticta Hance and Ilex
      chinensis Sim), surface soil, and lacustrine sediment. Method 1 employed an
      aminopropyl-bonded solid phase to selectively separate free n-FAs from
      extractable lipids, while Methods 2 and 3 involved alkali- and acid-catalysed
      chemical reactions in extractable lipids prior to isolation of the n-FAs.
      RESULTS: Methods 2 and 3 yielded higher amounts of C16-C24 n-FAs and of certain
      long-chain n-FAs than Method 1 due to the release of the corresponding ester
      bound n-FAs by saponification and transesterification reactions, respectively.
      Although additional ester-bound n-FAs were recovered by Methods 2 and 3, there
      were no significant differences in the delta(2)H results for all homologous n-FAs
      from the two plants and for mid- and long-chain n-FAs from the soil and sediment
      among the three pretreatment methods. CONCLUSIONS: Our study indicates that the
      three different pretreatment methods might not seriously influence the
      interpretations of delta(2)H values of sedimentary long-chain n-FAs as a
      terrestrial paleohydrological proxy; however, the release of ester-bound n-FAs by
      alkali- and acid-catalysed chemical reactions means that users should be cautious
      when interpreting and comparing distribution data of n-FAs from natural samples
      with different pretreatment protocols.

PMID- 26212277
TI  - Detection of explosives using a hollow cathode discharge ion source.
AB  - RATIONALE: For public security and safety, it is highly desirable to develop an
      ion source for the detection of explosives that is highly sensitive, compact in
      size, robust, and does not use any special carrier gases such as helium. In this
      work, a hollow cathode discharge (HCD) ion source was developed for the detection
      of explosives using ambient air as a carrier gas. METHODS: To detect nonvolatile
      and thermally unstable explosives with high sensitivities, a new HCD ion source
      was designed and coupled with an ion trap mass spectrometer. RESULTS: Five
      explosives--hexamethylene triperoxide diamine (HMTD), 1,3,5-trinitroperhydro
      1,3,5-triazine (RDX), pentaerythritol tetranitrate (PETN), nitroglycerin (NG) and
      trinitrotoluene (TNT)--were detected with limits of detection of lower than ng.
      The intensities of the NO3(-) adduct ions with RDX, PETN, and NG showed a marked
      increase with increase in ion source pressure in the range of 1-28 Torr.
      CONCLUSIONS: Because the major NOx(-) ions (x = 2, 3) produced in the plasma act
      as reagent ions in ion-molecule reactions of explosives, air is best suited as a
      carrier gas for the detection of explosives. It is proposed that the NOx(-) (x =
      2, 3) and O3 contributed to the formation of [TNT-H](-) and [TNT-NO](-) ions, via
      the reactions NOx(-) + TNT -> [TNT-H](-) + HNOx and [TNT](-) + O3 -> [TNT-NO](-)
      + NO2 + O2.

PMID- 26212278
TI  - Archaeological bone lipids as palaeodietary markers.
AB  - RATIONALE: Stable isotope analysis of archaeological and fossil bone samples can
      provide important insights into past environments, ecologies and diets. Previous
      studies have focused on stable carbon and nitrogen isotopes in bone collagen, or
      carbon isotopes in bone mineral (bioapatite). Carbon isotope analysis of lipids
      from archaeological bone has received much less attention, partly due to the lack
      of suitable methodologies allowing sufficient recovery of compounds for
      structural and isotopic characterisation. Here we show that lipids can be easily
      and reliably recovered from archaeological bone using a modified protocol, and
      that these provide complementary dietary information to other bone components.
      METHODS: Human and animal bones were obtained from a variety of archaeological
      contexts. Lipids were sequentially extracted using solvent extraction
      (dichloromethane/methanol), followed by acidified methanol extraction
      (methanol/H2SO4). The lipids were then analysed by gas chromatography/mass
      spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass
      spectrometry (GC/C/IRMS). RESULTS: Appreciable amounts of endogenous lipid were
      recovered from archaeological bone. Importantly, a comparison between compound
      specific and bulk collagen isotopic data shows that archaeological bone lipids
      reflect dietary input and can be used to distinguish between marine and
      terrestrial consumers, as well as between C3 and C4 plant consumers. Furthermore,
      the presence of essential fatty acids directly incorporated from diet to bone may
      provide additional palaeodietary information. CONCLUSIONS: Our findings suggest
      that archaeological bone lipids are a hitherto untapped resource of dietary
      information that offer additional insights to those gained from other isotopic
      analyses of bone.

PMID- 26212279
TI  - A non-targeted gas chromatography/electron capture negative ionization mass
      spectrometry selected ion monitoring screening method for polyhalogenated
      compounds in environmental samples.
AB  - RATIONALE: Many organohalogen compounds with adverse environmental properties
      have been detected in samples from marine ecosystems. Their quantitation is an
      important task in environmental analytical chemistry. However, the highly
      selective gas chromatography/mass spectrometry (GC/MS) selected ion monitoring
      (SIM) methods developed for this purpose only allow the detection of targeted
      compounds while unscreened compounds remain undiscovered. The detection of all
      polyhalogenated compounds in a sample requires the application of non-target
      methods. METHODS: We present a simple quadrupole-based GC/ECNI-MS-SIM method in
      which the entire high mass range is screened in eight GC runs using three time
      windows. Recently developed in the GC/EI-MS mode, this approach has now been
      adapted to the more sensitive GC/ECNI-MS mode. With this method we analyzed a
      fraction of a dolphin blubber sample from Australia and a sponge sample from the
      Mediterranean Sea on polychlorinated and polybrominated compounds and compared
      the results with the corresponding GC/EI-MS measurements. RESULTS: The non
      targeted GC/ECNI-MS-SIM chromatograms were clearly structured and hardly showed
      co-elutions. Altogether, >400 polyhalogenated compounds were detected in both
      samples. Many of them originated from unknown compounds. Several new or scarcely
      analyzed compounds could be tentatively identified. Most of the compounds were
      not detected with the non-target GC/EI-MS-SIM approach (~150 compounds detected).
      We also developed a two-dimensional plot in which the mass of the monoisotopic
      peak was plotted over the GC retention time and which was helpful for the
      identification of isomers. CONCLUSIONS: Since eight GC runs are required per
      sample, the method is not aimed for routine analysis. It is recommended as an
      initial screening method for the analysis of new sample matrices or samples from
      new regions. The non-targeted GC/ECNI-MS-SIM method benefits from the fact that
      it can be used with standard equipment.

PMID- 26212280
TI  - Reaction of arylium ions with the collision gas N2 in electrospray ionization
      mass spectrometry.
AB  - RATIONALE: The tandem mass spectra of many compounds contained peaks which could
      not have arisen from the precursor ion. Such peaks were found to be due to
      reaction of arylium ions with N2 in the collision cell. Therefore, this reaction
      was studied in detail with representative compounds. METHODS: Various classes of
      compounds were dissolved in acetonitrile/water/formic acid and studied by
      electrospray ionization mass spectrometry to record their MS(2) and pseudo-MS(3)
      spectra in a QqQ mass spectrometer and their accurate m/z values in an Orbitrap
      Elite instrument. Arylium ions were found to react with N2 in the collision cell.
      The reaction was confirmed by pseudo-MS(3) studies, by comparison with authentic
      diazonium ions, and by the pressure dependence of the product ion survival yield.
      RESULTS: Reactions of arylium ions with N2 were observed with p-toluenesulfonic
      acid, o-toluenesulfonamide, phenylphosphonic acid, phenol, aniline,
      aminonaphthalenes, benzoic acid, benzophenone, and other compounds. By using a
      QqQ mass spectrometer, we observed that the protonated compounds produce arylium
      ions, which then react with N2 to form diazonium ions. The diazonium ion was
      produced with N2 but not with Ar in the collision cell, and its abundance
      increased with increasing N2 pressure. CONCLUSIONS: Arylium ions generated from a
      wide variety of compounds in electrospray ionization tandem mass spectrometry may
      react with N2 to form diazonium ions. The abundance of the diazonium ions is
      affected by collision energy and N2 pressure. This reaction should be considered
      when annotating peaks in MS/MS libraries. Published in 2015. This article is a
      U.S. Government work and is in the public domain in the USA.

PMID- 26212281
TI  - A versatile cost-effective method for the analysis of fresh frozen tissue
      sections via matrix-assisted laser desorption/ionisation imaging mass
      spectrometry.
AB  - RATIONALE: There are currently multiple methods available for the preparation of
      fresh frozen tissue samples for analysis via matrix-assisted laser
      desorption/ionisation time-of-flight (MALDI-TOF) imaging mass spectrometry (IMS).
      Although these methods report excellent results, many are expensive automated
      approaches. With no published attempt to standardise less expensive manual
      processes, our work aims to provide a robust and repeatable method of sample
      preparation for MALDI-TOF-IMS that is applicable to a variety of tissue types,
      well explained, simple and cost effective. METHODS: Fresh frozen tissue was
      sectioned at 12 um and mounted onto liquid nitrocellulose coated slides, washed
      in a graded alcohol series and then mounted into a modified sublimation
      apparatus. Matrix is deposited onto the slide to achieve a desired coating of 0.2
      mg/cm(2). Once coated, the slide is mounted into a custom-built vapor chamber and
      recrystallised with 50% acetonitrile (ACN), 0.1% trifluoroacetic acid (TFA) for 1
      h at 37 degrees C. The slide is then analysed using MALDI-IMS. RESULTS: We have
      successfully implemented this method for a host of tissue samples, including
      brain, liver, kidney and heart, with no variation in relative spectra or
      processing method required. When the protocol is followed correctly, sublimations
      and recrystallisations are highly predictable with limited variation between
      samples and a very low failure rate. Additional apparatuses can be easily
      constructed by following the included instructions, that perform as per
      specifications with no variation. CONCLUSIONS: We believe that we have described
      a complete protocol for MALDI-IMS that is easy to use and highly reproducible.
      The lack of expensive commercially available equipment makes this process very
      cheap with a relatively low initial outlay and our hope is that more laboratories
      will begin IMS-based avenues of research based on the work we have performed.

PMID- 26212282
TI  - Tracing the nitrogen metabolites of glycine using (15)N-glycine and mass
      spectrometry.
AB  - RATIONALE: Glycine is the smallest amino acid used in protein synthesis, but it
      is also a very important precursor for the biosynthesis of other nitrogen
      containing metabolites, such as purine nucleosides and nucleotides for synthesis
      of RNA, DNA etc. Abnormalities in glycine metabolism therefore cause diseases
      such as cancer. A quick and unambiguous method to trace the metabolites arising
      from glycine is required for targeting defect points within metabolic networks.
      METHODS: This paper describes a method for using (15)N-glycine to culture A549
      cancer cells for use with high-resolution mass spectrometry (HRMS) and tandem
      mass spectrometry (HRMS(2)) that can detect the (M+1)/M pair peaks appearing in
      the cell metabolites. The 1 Da difference in the pair peaks can be used to point
      out and identify the nitrogen metabolites of glycine. RESULTS: Thirteen nitrogen
      containing metabolites derived from glycine were confirmed. Among them were
      metabolites containing purine, such as adenine, adenosine, AMP, ADP, ATP, S
      adenosylmethionine and gamma-glutathione; these were the most sensitive to the
      (15)N-glycine-enrichment technique. Therefore, they are promising biomarkers for
      monitoring the glycine metabolism network. CONCLUSIONS: The method developed here
      could be applied to investigations of metabolism of other amino acids, and for
      drug discovery studies targeting the enzymes related to amino acid metabolism.

PMID- 26212283
TI  - Bottom-up proteomic analysis of single HCT 116 colon carcinoma multicellular
      spheroids.
AB  - RATIONALE: Proteomic analysis of single multicellular spheroids has not been
      previously reported. As three-dimensional cell cultures are an increasingly
      popular model system for biological research, there is interest in obtaining
      proteomic profiles of these samples. We investigated the proteome of single HCT
      116 multicellular spheroids using protocols optimized for small sample sizes.
      METHODS: Six biological replicates were analyzed via microscopy for size. Total
      protein content was assessed via the bicinchoninic acid assay (BCA assay). Five
      separate biological replicate spheroids were analyzed via mass spectrometry in
      technical duplicate. An ultra-performance liquid chromatography (UPLC) system
      coupled with an LTQ Orbitrap Velos was used for peptide separation, analysis, and
      identification. RESULTS: The average diameter of six replicate HCT 116 spheroids
      was 940 +/- 30 um and the average total protein amount was determined to be 39 +/
      4 ug. At least 1300 protein groups were identified in each single LC/MS/MS run
      with 10% of the material from each single spheroid loaded. Database search
      results showed variation between spheroid protein group identifications. Pearson
      correlations show that the disparity in identifications is due to random
      variations in spectra and protocol. CONCLUSIONS: We detected more than 1350
      protein groups in each replicate HCT 116 spheroid. While some variation was
      detected between replicates, differences in the number of protein groups
      identified were determined to be the result of random variations in mass spectra
      acquisition.

PMID- 26212284
TI  - Paired single residue-transposed Lys-N and Lys-C digestions for label-free
      identification of N-terminal and C-terminal MS/MS peptide product ions: ultrahigh
      resolution Fourier transform ion cyclotron resonance mass spectrometry and tandem
      mass spectrometry for peptide de novo sequencing.
AB  - RATIONALE: Paired Lys-N and Lys-C proteases produce peptides of identical mass
      and similar retention time, but different tandem mass spectra. Data from these
      parallel experiments provide constraints that are applied before data analysis.
      With this approach, we can find matched spectra before analysis, distinguish ion
      type, and determine residue level confidence. METHODS: Aliquots are digested
      separately by Lys-N and Lys-C peptidases, and analyzed by reversed-phase nano
      flow liquid chromatography, collision-induced dissociation, and 14.5 T Fourier
      transform ion cyclotron resonance mass spectrometry. Matched pairs of
      fragmentation spectra with equal precursor mass and similar retention times from
      each digestion are compared, leveraging single-residue transposed information
      with independent interferences to confidently identify fragment ion type,
      residues, and peptides. The paired spectra are solved together as a single de
      novo sequencing problem. RESULTS: Two pairs of spectra of a de novo sequenced 18
      mer are presented. In one example, the 18-mer has coverage of all residues except
      the N- and C- terminal lysines and their adjacent residues. The confidence level
      is high due to six pairs of transposed ions. In the other example, the coverage
      is incomplete. Nonetheless, nine pairs of transposed ions facilitate
      identification of two trimer sequence tags with high confidence, one with medium
      confidence, and additional sequence information with residue-by-residue
      confidence, thus demonstrating the value of residue-by-residue confidence.
      CONCLUSIONS: Sequence identity and variability, such as post-translational
      modifications (PTMs), are essential to understanding biological function and
      disease. The present method facilitates discovery of new peptides with multiple
      levels of confidence, promises potential characterization of PTMs, and validates
      peptides from databases. Independent validation may be of interest for a number
      of applications.

PMID- 26212285
TI  - Variability of higher trophic level stable isotope data in space and time--a case
      study in a marine ecosystem.
AB  - RATIONALE: 1In shelf and coastal ecosystems, planktonic and benthic trophic
      pathways differ in their carbon stable isotope ratios (delta(13)C values) and
      nitrogen stable isotope ratios (delta(15)N values) and they increase predictably
      with trophic level. Stable isotope data are therefore used as a tool to study
      food webs in shelf and coastal ecosystems, and to assess the diets and foraging
      behaviour of predators. However, spatial differences and temporal changes in
      prevailing environmental conditions and prey abundance may lead to considerable
      heterogeneity in stable isotope values measured in focal animal species. METHODS:
      Here we assess spatial and temporal variability of delta(13)C and delta(15)N
      values in tissue samples of fish, squid and crustacean species captured over
      three years during research cruises close to the Falkland Islands, Southwest
      Atlantic. RESULTS: Both in delta(15)N values and especially in delta(13)C values,
      intra-species differences were large and often exceeded inter-species
      differences. Spatial patterns were weak, albeit statistically significant. The
      distribution of delta(13)C values was related to latitude, while the delta(15)N
      values varied with longitude. The distance from the coast and depth of catch
      influenced both delta(13)C and delta(15)N values. However, the importance of
      temporal variability greatly exceeded that of spatial variability. In addition to
      a moderate overall seasonal effect, we found that species differed strongly in
      their specific seasonal changes. CONCLUSIONS: Seasonal differences in the
      relative position of species or species groups in the C-N isotope space suggest
      changes in the utilisation of planktonic vs. benthic trophic pathways, indicating
      flexible foraging strategies in response to variable environmental conditions.
      These seasonal differences should be taken into account when analysing higher
      trophic level feeding ecology with stable isotope analysis.

PMID- 26212286
TI  - Differentiation of prototropic ions in regioisomeric caffeoyl quinic acids by
      electrospray ion mobility mass spectrometry.
AB  - RATIONALE: A series of dietary important regioisomeric chlorogenic acids were
      investigated by ion mobility mass spectrometry (IM-MS). The existence of
      prototropic isomers separated in the drift dimension was observed and
      investigated further using tandem mass spectrometry (MS/MS) and compared with
      suitable synthetic analogues. METHODS: Using a quadrupole ion mobility time-of
      flight mass spectrometer, the IM-MS and IM-MS/MS spectra of selected chlorogenic
      acids were recorded in the negative ion mode and compared with synthetic
      analogues. RESULTS: Regioisomeric di- and monocaffeoyl quinic acids can be
      readily separated and investigated using IM-MS. Comparison of drift times allows
      assignment of the regiochemistry of precursor ions as well as for fragment ions.
      For 5-caffeoyl quinic acid the existence of prototropic ions was suggested and
      probed using synthetic analogues, unable to show this type of isomerism. These
      investigations suggest the presence of prototropic isomers with carboxylate and
      phenolate sites, respectively. CONCLUSIONS: We report on IM-MS measurements on
      regioisomeric mono- and dicaffeoyl quinic acids, which are important dietary
      natural products. Both classes of compounds can be readily separated by IM-MS in
      the drift time dimension and, following MS(2) experiments, fragment ion
      regiochemistry unambiguously determined. 5-Caffeoyl quinic acid shows two IM-MS
      signals, which we assign to prototropic isomers after comparison with suitable
      synthetic analogues, with a negative charge located at the carboxalate or
      phenolate functionality, respectively.

PMID- 26212287
TI  - Mass spectrometry based detection of glutathione with sensitivity for single-cell
      analysis.
AB  - RATIONALE: Glutathione (GSH) is a very important molecule that participates in
      various physiologically important events. Depletion of cellular GSH has been
      suggested as a biomarker of early stage of cell injury. Assessment of GSH with
      high selectivity and sensitivity is in demand in many fields of life sciences.
      METHODS: Cell lysates were deproteinated by 5-sulfosalicylic acid. Glutathione
      was derivatized with monobromobimane to form a GSH conjugate. S-Hexylglutathione
      was employed as internal standard. The resulting samples were analyzed using a
      high-performance liquid chromatography/electrospray ionization tandem mass
      spectrometry (HPLC/ESI-MS/MS) system. RESULTS: The limit of detection was as low
      as 500 amol with high selectivity. The approach was sensitive enough to detect
      GSH content in a single human erythrocyte. The technique is the most sensitive
      approach among the reported MS-based GSH assays. CONCLUSIONS: A monobromobimane
      derivatization and mass spectrometry based method was developed for the
      assessment of GSH. The derivatized GSH was chemically stable against
      autooxidation. With the great selectivity and sensitivity, the approach is
      anticipated to serve as a routine method for assessment of GSH and possibly other
      important endogenous low molecular weight thiols.

PMID- 26212288
TI  - In-source cloud ion mobility mass spectrometry.

PMID- 26212290
TI  - BMSS@50: a community that continues to deliver British science.

PMID- 26212289
TI  - A cross-omics analysis of acetaminophen-induced hepatotoxicity in rat liver.

PMID- 26212291
TI  - Mutation Research/Genetic Toxicology and Environmental Mutagenesis. JaCVAM
      organized international validation study of the in vivo rat alkaline comet assay.
      Preface.

PMID- 26212292
TI  - The JaCVAM-organized international validation study of the in vivo rodent
      alkaline comet assay.

PMID- 26212294
TI  - The JaCVAM international validation study on the in vivo comet assay: Selection
      of test chemicals.
AB  - The Japanese Center for the Validation of Alternative Methods (JaCVAM) sponsored
      an international prevalidation and validation study of the in vivo rat alkaline
      pH comet assay. The main objective of the study was to assess the sensitivity and
      specificity of the assay for correctly identifying genotoxic carcinogens, as
      compared with the traditional rat liver unscheduled DNA synthesis assay. Based on
      existing carcinogenicity and genotoxicity data and chemical class information, 90
      chemicals were identified as primary candidates for use in the validation study.
      From these 90 chemicals, 46 secondary candidates and then 40 final chemicals were
      selected based on a sufficiency of carcinogenic and genotoxic data, differences
      in chemical class or genotoxic or carcinogenic mode of action (MOA),
      availability, price, and ease of handling. These 40 chemicals included 19
      genotoxic carcinogens, 6 genotoxic non-carcinogens, 7 non-genotoxic carcinogens
      and 8 non-genotoxic non-carcinogens. "Genotoxicity" was defined as positive in
      the Ames mutagenicity test or in one of the standard in vivo genotoxicity tests
      (primarily the erythrocyte micronucleus assay). These chemicals covered various
      chemicals classes, MOAs, and genotoxicity profiles and were considered to be
      suitable for the purpose of the validation study. General principles of chemical
      selection for validation studies are discussed. 

PMID- 26212293
TI  - JaCVAM-organized international validation study of the in vivo rodent alkaline
      comet assay for the detection of genotoxic carcinogens: I. Summary of pre
      validation study results.
AB  - The in vivo rodent alkaline comet assay (comet assay) is used internationally to
      investigate the in vivo genotoxic potential of test chemicals. This assay,
      however, has not previously been formally validated. The Japanese Center for the
      Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP
      Interagency Center for the Evaluation of Alternative Toxicological Methods
      (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative
      Methods (ICCVAM), the European Centre for the Validation of Alternative Methods
      (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis
      Study Group (JEMS/MMS), organized an international validation study to evaluate
      the reliability and relevance of the assay for identifying genotoxic carcinogens,
      using liver and stomach as target organs. The ultimate goal of this validation
      effort was to establish an Organisation for Economic Co-operation and Development
      (OECD) test guideline. The purpose of the pre-validation studies (i.e., Phase 1
      through 3), conducted in four or five laboratories with extensive comet assay
      experience, was to optimize the protocol to be used during the definitive
      validation study. 

PMID- 26212295
TI  - JaCVAM-organized international validation study of the in vivo rodent alkaline
      comet assay for detection of genotoxic carcinogens: II. Summary of definitive
      validation study results.
AB  - The in vivo rodent alkaline comet assay (comet assay) is used internationally to
      investigate the in vivo genotoxic potential of test chemicals. This assay,
      however, has not previously been formally validated. The Japanese Center for the
      Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP
      Interagency Center for the Evaluation of Alternative Toxicological Methods
      (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative
      Methods (ICCVAM), the European Centre for the Validation of Alternative Methods
      (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis
      Study Group (JEMS/MMS), organized an international validation study to evaluate
      the reliability and relevance of the assay for identifying genotoxic carcinogens,
      using liver and stomach as target organs. The ultimate goal of this exercise was
      to establish an Organisation for Economic Co-operation and Development (OECD)
      test guideline. The study protocol was optimized in the pre-validation studies,
      and then the definitive (4th phase) validation study was conducted in two steps.
      In the 1st step, assay reproducibility was confirmed among laboratories using
      four coded reference chemicals and the positive control ethyl methanesulfonate.
      In the 2nd step, the predictive capability was investigated using 40 coded
      chemicals with known genotoxic and carcinogenic activity (i.e., genotoxic
      carcinogens, genotoxic non-carcinogens, non-genotoxic carcinogens, and non
      genotoxic non-carcinogens). Based on the results obtained, the in vivo comet
      assay is concluded to be highly capable of identifying genotoxic chemicals and
      therefore can serve as a reliable predictor of rodent carcinogenicity. 

PMID- 26212296
TI  - Alkaline comet assay in liver and stomach, and micronucleus assay in bone marrow,
      from rats treated with 2-acetylaminofluorene, azidothymidine, cisplatin, or
      isobutyraldehyde.
AB  - As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)
      initiative international validation study of the in vivo rat alkaline comet assay
      (comet assay), we examined the ability of the assay to determine the genotoxicity
      of 2-acetylaminofluorene (AAF), azidothymidine (AZT), cisplatin (CPN), and
      isobutyraldehyde (IBA) in liver and glandular stomach of male Sprague-Dawley
      rats. Rats were given oral doses of test compound or control once daily for three
      days. High dose levels were approximately maximum tolerated doses and were based
      on preliminary range-finding studies. Tissues were harvested 3h after the final
      dose (48h after the initial dose). A bone marrow micronucleus assay (MN) was also
      conducted on the rats treated with AZT, CPN, and IBA. Acute toxic effects of
      treatment were determined primarily through histomorphologic analysis of liver
      and stomach but also by body weight and serum liver enzyme changes. The comet
      assay was conducted on fresh tissue preparations but frozen samples from two
      studies were also assayed. Statistically significant dose-related differences in
      comet % DNA in tail were found in liver and stomach for the genotoxin AZT and in
      liver for the genotoxin CPN, but not in liver or stomach for the non-genotoxin
      IBA. Statistically significant differences in % DNA in tail were measured in
      liver for the low and mid dose of the genotoxin AAF, but not the high dose. The
      comet assays of frozen liver suspensions from CPN- and AAF-treated rats yielded
      comparable results to the assays of fresh preparations. There were no indications
      of significant toxicity induced by any treatment. The micronucleus assay was
      positive for CPN and AZT and negative for IBA. In conclusion, the in vivo comet
      assay is capable of detecting genotoxic effects of a variety of chemicals and may
      fill an important role in the genotoxicity test battery. 

PMID- 26212297
TI  - Combination comet/micronucleus assay validation performed by BioReliance under
      the JaCVAM initiative.
AB  - In the international validation study of the in vivo rat alkaline comet assay
      (comet assay), the Japanese Center for the Validation of Alternative Methods
      (JaCVAM) provided three coded chemicals to BioReliance, 1,3-dichloropropene,
      ethionamide and busulfan, to be tested in a combined in vivo comet/micronucleus
      assay. Induction of DNA damage (comet) in liver, stomach and jejunum (1,3
      dichloropropene only) cells, and induction of MNPCEs in bone marrow, were
      examined in male Sprague-Dawley (Hsd:SD) rats following oral administration of
      the test chemical for three consecutive days. A dose range finding (DRF) test was
      performed with each chemical to determine the maximum tolerated dose (MTD). Based
      on the results of the DRF test; 1,3-dichloropropene was tested at 50, 100 and 200
      mg/kg/day; ethionamide was tested at 125, 250 and 500 mg/kg/day, and busulfan was
      tested at 10, 20 and 40 mg/kg/day. The results indicated that 1,3-dichloropropene
      induced DNA damage only in liver cells at all three test article doses, while no
      effects were observed in the stomach and jejunum cells. Additionally, it did not
      increase MNPCEs in the bone marrow. 1,3-Dichloropropene was concluded to be
      negative in the MN assay but positive in the comet assay. Ethionamide did not
      induce DNA damage in liver. However, in stomach, statistically significant
      decreases (although still within historical range) in % tail DNA at all test
      article doses compared to the vehicle control were observed. There was no
      increase in MNPCEs in the bone marrow. Thus, ethionamide was concluded to be
      negative in the comet/MN combined assay. Busulfan did not induce DNA damage in
      any of the organs tested (liver and stomach) but it did induce a significant
      increase in MNPCEs in the bone marrow. Busulfan was concluded to be negative in
      the comet assay but positive in the MN assay.

PMID- 26212298
TI  - p-Chloroaniline, t-butylhydroquinone, and methyl carbamate: Rat in vivo comet
      test, JaCVAM trial phase 4.2.
AB  - As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)
      initiative international validation study of in vivo rat alkaline comet assay, we
      examined p-Chloroaniline, t-butylhydroquinone, and methyl carbamate. All test
      materials and controls were dosed orally by gavage. p-Chloroaniline produced a
      statistically significant increase in the mean and median % tail intensity which
      was also outside of the historical control range in the liver and stomach of
      Sprague-Dawley rats. t-Butylhydroquinone caused a statistically significant
      increase in the mean % tail intensity in the liver and stomach and a
      statistically significant increase in the median % tail intensity in the liver;
      however, these results are not considered to be biologically significant as all
      values obtained fell within the current vehicle historical control range and
      within the negative control range for mean % tail intensity set by the Validation
      Management Team (VMT) as a requirement for an acceptable assay. Methyl carbamate
      did not induce a statistically significant change in the mean or median % tail
      intensity in either liver or stomach. 

PMID- 26212299
TI  - In vivo comet assay of acrylonitrile, 9-aminoacridine hydrochloride monohydrate
      and ethanol in rats.
AB  - As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)
      initiative international validation study of the in vivo rat alkaline comet
      assay, we examined the ability of acrylonitrile, 9-aminoacridine hydrochloride
      monohydrate (9-AA), and ethanol to induce DNA damage in the liver and glandular
      stomach of male rats. Acrylonitrile is a genotoxic carcinogen, 9-AA is a
      genotoxic non-carcinogen, and ethanol is a non-genotoxic carcinogen. Positive
      results were obtained in the liver cells of male rats treated with known
      genotoxic compounds, acrylonitrile and 9-AA. 

PMID- 26212300
TI  - Assessment of the in vivo genotoxicity of cadmium chloride, chloroform, and D,L
      menthol as coded test chemicals using the alkaline comet assay.
AB  - As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)
      international validation study of in vivo rat alkaline comet assays, we examined
      cadmium chloride, chloroform, and D,L-menthol under blind conditions as coded
      chemicals in the liver and stomach of Sprague-Dawley rats after 3 days of
      administration. Cadmium chloride showed equivocal responses in the liver and
      stomach, supporting previous reports of its poor mutagenic potential and non
      carcinogenic effects in these organs. Treatment with chloroform, which is a non
      genotoxic carcinogen, did not induce DNA damage in the liver or stomach. Some
      histopathological changes, such as necrosis and degeneration, were observed in
      the liver; however, they did not affect the comet assay results. D,L-Menthol, a
      non-genotoxic non-carcinogen, did not induce liver or stomach DNA damage. These
      results indicate that the comet assay can reflect genotoxic properties under
      blind conditions.

PMID- 26212301
TI  - Evaluation of methyl methanesulfonate, 2,6-diaminotoluene and 5-fluorouracil:
      Part of the Japanese center for the validation of alternative methods (JaCVAM)
      international validation study of the in vivo rat alkaline comet assay.
AB  - As a part of the Japanese Center for the Validation of Alternative Methods
      (JaCVAM)-initiative international validation study of the in vivo rat alkaline
      comet assay (comet assay), we examined methyl methanesulfonate, 2,6
      diaminotoluene, and 5-fluorouracil under coded test conditions. Rats were treated
      orally with the maximum tolerated dose (MTD) and two additional descending doses
      of the respective compounds. In the MMS treated groups liver and stomach showed
      significantly elevated DNA damage at each dose level and a significant dose
      response relationship. 2,6-diaminotoluene induced significantly elevated DNA
      damage in the liver at each dose and a statistically significant dose-response
      relationship whereas no DNA damage was obtained in the stomach. 5-fluorouracil
      did not induce DNA damage in either liver or stomach. 

PMID- 26212302
TI  - Evaluation of 4,4'-diaminodiphenyl ether in the rat comet assay: Part of the
      Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative
      international validation study of in vivo rat alkaline comet assay.
AB  - As a part of the Japanese Center for the Validation of Alternative Methods
      (JaCVAM)-initiative international validation study of the in vivo rat alkaline
      comet assay, 4,4'-diaminodiphenyl ether (DPE), a known rodent genotoxic
      carcinogen, was tested in this laboratory. Sprague Dawley rats (7-9 weeks of age)
      were given three oral doses of DPE, 24 and 21 h apart and liver or stomach
      sampled 3h after the final dose. Under the conditions of the test, no increases
      in DNA damage in liver and stomach were observed with DPE (up to 200 mg/kg/day).
      A dose-dependent decrease in DNA migration, compared to vehicle controls, was
      noted for DPE in rat stomach. Further analysis is required to elucidate fully
      whether this decrease is a consequence of the mode of action or due to the
      toxicity of DPE. What is perhaps surprising is the inability of the comet assay
      to detect a known rat genotoxic carcinogen in liver. Further investigation is
      needed to clarify whether this apparent lack of response results from limited
      tissue exposure or metabolic differences between species. This finding highlights
      a need for careful consideration of study design when evaluating assay
      performance as a measure of in vivo genotoxicity.

PMID- 26212303
TI  - Optimal dose selection of N-methyl-N-nitrosourea for the rat comet assay to
      evaluate DNA damage in organs with different susceptibility to cytotoxicity.
AB  - The in vivo rodent alkaline comet assay (comet assay) is a promising technique to
      evaluate DNA damage in vivo. However, there is no agreement on a method to
      evaluate DNA damage in organs where cytotoxicity is observed. As a part of the
      Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative
      international validation study of the comet assay, we examined DNA damage in the
      liver, stomach, and bone marrow of rats given three oral doses of N-methyl-N
      nitrosourea (MNU) up to the maximum tolerated dose based on systemic toxicity.
      MNU significantly increased the % tail DNA in all the organs. Histopathological
      analysis showed no cytotoxic effect on the liver, indicating clearly that MNU has
      a genotoxic potential in the liver. In the stomach, however, the cytotoxic
      effects were very severe at systemically non-toxic doses. Low-dose MNU
      significantly increased the % tail DNA even at a non-cytotoxic dose, indicating
      that MNU has a genotoxic potential also in the stomach. Part of the DNA damage at
      cytotoxic doses was considered to be a secondary effect of severe cell damage. In
      the bone marrow, both the % tail DNA and incidence of micronucleated
      polychromatic erythrocytes significantly increased at non-hematotoxic doses,
      which were different from the non-cytotoxic doses for liver and stomach. These
      findings indicate that an optimal dose for detecting DNA damage may vary among
      organs and that careful attention is required to select an optimum dose for the
      comet assay based on systemic toxicity such as mortality and clinical
      observations. The present study shows that when serious cytotoxicity is suggested
      by increased % hedgehogs in the comet assay, histopathological examination should
      be included for the evaluation of a positive response. 

PMID- 26212304
TI  - Genotoxicity evaluation of benzene, di(2-ethylhexyl) phthalate, and trisodium
      ethylenediamine tetraacetic acid monohydrate using a combined rat
      comet/micronucleus assays.
AB  - As a part of the Japanese Center for the Validation of Alternative Methods
      (JaCVAM)-initiative international validation study of the in vivo alkaline comet
      assay (comet assay), we examined DNA damage in the liver, stomach, and bone
      marrow of rats dosed orally three times with up to 2000 mg/kg of benzene, di(2
      ethylhexyl) phthalate, and trisodium ethylenediamine tetraacetic acid
      monohydrate. All three compounds gave negative results in the liver and stomach.
      In addition, a bone marrow comet and micronucleus analysis revealed that benzene,
      but not di(2-ethylhexyl) phthalate or trisodium ethylenediamine tetraacetic acid
      monohydrate induced a significant increase in the median % tail DNA and
      micronucleated polychromatic erythrocytes, compared with the respective
      concurrent vehicle control. These results were in good agreement with the
      previously reported genotoxicity findings for each compound. The present study
      has shown that combining the micronucleus test with the comet assay and carrying
      out these analyses simultaneously is effective in clarifying the mechanism of
      action of genotoxic compounds such as benzene.

PMID- 26212306
TI  - Evaluation of p-phenylenediamine, o-phenylphenol sodium salt, and 2,4
      diaminotoluene in the rat comet assay as part of the Japanese Center for the
      Validation of Alternative Methods (JaCVAM)-initiated international validation
      study of in vivo rat alkaline comet assay.
AB  - As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)
      initiated international validation study of in vivo rat alkaline comet assay
      (comet assay), p-phenylenediamine dihydrochloride (PPD), o-phenylphenol sodium
      salt (OPP), and 2,4-diaminotoluene (2,4-DAT), were analyzed in this laboratory as
      coded test chemicals. Male Sprague-Dawley rats (7-9 weeks of age) were given
      three oral doses of the test compounds, 24 and 21 h apart and liver and stomach
      were sampled 3h after the final dose administration. Under the conditions of the
      test, no increases in DNA damage were observed in liver and stomach with PPD and
      OPP up to 100 and 1000 mg/kg/day, respectively. 2,4-DAT, a known genotoxic
      carcinogen, induced a weak but reproducible, dose-related and statistically
      significant increase in DNA damage in liver cells while no increases were
      observed in stomach cells.

PMID- 26212305
TI  - Results of the International Validation of the in vivo rodent alkaline comet
      assay for the detection of genotoxic carcinogens: Individual data for 1,2
      dibromoethane, p-anisidine, and o-anthranilic acid in the 2nd step of the 4th
      phase Validation Study under the JaCVAM initiative.
AB  - As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)
      initiative International Validation Study of an in vivo rat alkaline comet assay,
      we examined 1,2-dibromoethane (DBE), p-anisidine (ASD), and o-anthranilic acid
      (ANT) to investigate the effectiveness of the comet assay in detecting genotoxic
      carcinogens. Each of the three test chemicals was administered to 5 male Sprague
      Dawley rats per group by oral gavage at 48, 24, and 3h before specimen
      preparation. Single cells were collected from the liver and glandular stomach at
      3h after the final dosing, and the specimens prepared from these two organs were
      subjected to electrophoresis under alkaline conditions (pH>13). The percentage of
      DNA intensity in the comet tail was then assessed using an image analysis system.
      A micronucleus (MN) assay was also conducted using these three test chemicals
      with the bone marrow (BM) cells collected from the same animals simultaneously
      used in the comet assay, i.e., combination study of the comet assay and BM MN
      assay. A genotoxic (Ames positive) rodent carcinogen, DBE gave a positive result
      in the comet assay in the present study, while a genotoxic (Ames positive) non
      carcinogen, ASD and a non-genotoxic (Ames negative) non-carcinogen, ANT showed
      negative results in the comet assay. All three chemicals produced negative
      results in the BM MN assay. While the comet assay findings in the present study
      were consistent with those obtained from the rodent carcinogenicity studies for
      the three test chemicals, we consider the positive result in the comet assay for
      DBE to be particularly meaningful, given that this chemical produced a negative
      result in the BM MN assay. Therefore, the combination study of the comet assay
      and BM MN assay is a useful method to detect genotoxic carcinogens that are
      undetectable with the BM MN assay alone. 

PMID- 26212307
TI  - Use of a standardized JaCVAM in vivo rat comet assay protocol to assess the
      genotoxicity of three coded test compounds; ampicillin trihydrate, 1,2
      dimethylhydrazine dihydrochloride, and N-nitrosodimethylamine.
AB  - As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)
      initiative international validation study of the in vivo rat alkaline comet assay
      (comet assay), our laboratory examined ampicillin trihydrate (AMP), 1,2
      dimethylhydrazine dihydrochloride (DMH), and N-nitrosodimethylamine (NDA) using a
      standard comet assay validation protocol (v14.2) developed by the JaCVAM
      validation management team (VMT). Coded samples were received by our laboratory
      along with basic MSDS information. Solubility analysis and range-finding
      experiments of the coded test compounds were conducted for dose selection. Animal
      dosing schedules, the comet assay processing and analysis, and statistical
      analysis were conducted in accordance with the standard protocol. Based upon our
      blinded evaluation, AMP was not found to exhibit evidence of genotoxicity in
      either the rat liver or stomach. However, both NDA and DMH were observed to cause
      a significant increase in % tail DNA in the rat liver at all dose levels tested.
      While acute hepatoxicity was observed for these compounds in the high dose group,
      in the investigators opinion there were a sufficient number of consistently
      damaged/measurable cells at the medium and low dose groups to judge these
      compounds as genotoxic. There was no evidence of genotoxicity from either NDA or
      DMH in the rat stomach. In conclusion, our laboratory observed increased DNA
      damage from two blinded test compounds in rat liver (later identified as
      genotoxic carcinogens), while no evidence of genotoxicity was observed for the
      third blinded test compound (later identified as a non-genotoxic, non
      carcinogen). This data supports the use of a standardized protocol of the in vivo
      comet assay as a cost-effective alternative genotoxicity assay for regulatory
      testing purposes. 

PMID- 26212308
TI  - Investigation of sodium arsenite, thioacetamide, and diethanolamine in the
      alkaline comet assay: Part of the JaCVAM comet validation exercise.
AB  - As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)
      initiative international validation study of the in vivo rat alkaline comet assay
      (comet assay), we examined sodium arsenite, thioacetamide, and diethanolamine.
      Using the JaCVAM approved study protocol version 14.2, each chemical was tested
      in male rats up to maximum tolerated dose levels and DNA damage in the liver and
      stomach was assessed approximately 3h after the final administration by gavage.
      Histopathology assessments of liver and stomach sections from the same animals
      were also examined for evidence of cytotoxicity or necrosis. No evidence of DNA
      damage was observed in the stomach of animals treated with sodium arsenite at
      7.5, 15, or 30 mg/kg/day. However, equivocal findings were found in the liver,
      where increases in DNA migration were observed in two independent experiments,
      but not in all treated animals and not at the same dose levels. Thioacetamide
      caused an increase in DNA migration in the stomach of rats treated at 19, 38, and
      75 mg/kg/day, but not in the liver, despite evidence of marked hepatotoxicity
      following histopathology assessments. No evidence of DNA damage was observed in
      the stomach or liver of animals treated with diethanolamine at 175, 350, or 700
      mg/kg/day.

PMID- 26212310
TI  - Re-analysis results using medians of the data from the JaCVAM-organized
      international validation study of the in vivo rat alkaline comet assay.
AB  - The data from the JaCVAM-organized international validation study of the in vivo
      rat alkaline comet assay were reported and analyzed statistically using the
      simple means of % tail DNA. However, OECD test guideline TG 489 recommends use of
      the median for data analysis due to the hierarchical nature of the data.
      Comparison between the simple mean approach and the median based approach for
      positive/negative/equivocal chemical calls was conducted using the % tail DNA
      data for the 40 chemicals tested in the JaCVAM-organized international validation
      study of the in vivo rat alkaline comet assay, using liver and stomach as target
      organs. In the liver, two genotoxic chemicals, o-anisidine and 9-aminoacridine
      hydrochloride monohydrate, were positive using the median based approach but
      negative using the simple mean approach, and two genotoxic chemicals, 2
      acetylaminofluorene and busulfan were equivocal using the median based approach
      but negative using the simple mean approach. In contrast, cadmium chloride
      (genotoxic carcinogen) was equivocal in both organs using the median based
      approach, while positive and equivocal in liver and stomach, respectively, using
      the simple mean approach. Two data sets of sodium arsenite showed equivocal and
      negative results for liver using the median based approach, although both data
      sets were equivocal using the simple mean approach. Overall, there are no large
      differences in terms of the genotoxic call between both approaches. However, the
      median based approach recommended in OECD TG 489 has an advantage toward higher
      precision within the groups treated with a test chemical, whereas the approach
      might show the lower values for the effect. 

PMID- 26212309
TI  - Comet assay evaluation of six chemicals of known genotoxic potential in rats.
AB  - As a part of an international validation of the in vivo rat alkaline comet assay
      (comet assay) initiated by the Japanese Center for the Validation of Alternative
      Methods (JaCVAM) we examined six chemicals for potential to induce DNA damage: 2
      acetylaminofluorene (2-AAF), N-nitrosodimethylamine (DMN), o-anisidine, 1,2
      dimethylhydrazine dihydrochloride (1,2-DMH), sodium chloride, and sodium
      arsenite. DNA damage was evaluated in the liver and stomach of 7- to 9-week-old
      male Sprague Dawley rats. Of the five genotoxic carcinogens tested in our
      laboratory, DMN and 1,2-DMH were positive in the liver and negative in the
      stomach, 2-AAF and o-anisidine produced an equivocal result in liver and negative
      results in stomach, and sodium arsenite was negative in both liver and stomach.
      1,2-DMH and DMN induced dose-related increases in hedgehogs in the same tissue
      (liver) that exhibited increased DNA migration. However, no cytotoxicity was
      indicated by the neutral diffusion assay (assessment of highly fragmented DNA) or
      histopathology in response to treatment with any of the tested chemicals.
      Therefore, the increased DNA damage resulting from exposure to DMN and 1,2-DMH
      was considered to represent a genotoxic response. Sodium chloride, a non
      genotoxic non-carcinogen, was negative in both tissues as would be predicted.
      Although only two (1,2-DMH and DMN) out of five genotoxic carcinogens produced
      clearly positive results in the comet assay, the results obtained for o-anisidine
      and sodium arsenite in liver and stomach cells are consistent with the known mode
      of genotoxicity and tissue specificity exhibited by these carcinogens. In
      contrast, given the known genotoxic mode-of-action and target organ
      carcinogenicity of 2-AAF, it is unclear why this chemical failed to convincingly
      increase DNA migration in the liver. Thus, the results of the comet assay
      validation studies conducted in our laboratory were considered appropriate for
      five out of the six test chemicals. 

PMID- 26212311
TI  - Polymerase chain reaction-restriction fragment length polymorphism method for
      differentiation of uropathogenic specific protein gene types.
AB  - The putative pathogenicity island (PAI) containing the uropathogenic specific
      protein (usp) gene and three small open reading frames (orfU1, orfU2, and orfU3)
      encoding 98, 97, and 96 amino acid proteins is widely distributed among
      uropathogenic Escherichia coli (UPEC) strains. This PAI was designated as PAIusp.
      Sequencing analysis of PAIusp has revealed that the usp gene can be divided into
      two types - uspI and uspII - based on sequence variation at the 3' terminal
      region and the number and position of orfUs differ from strain to strain. Based
      on usp gene types and orfU sequential patterns, PAIusp can be divided into four
      subtypes. Subtyping of PAIusp is a useful method to characterize UPEC strains. In
      this study, we developed a polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method to differentiate usp gene types. This method could
      correctly identify the usp gene type in usp-positive UPEC strains in our
      laboratory. 

PMID- 26212312
TI  - Structures of intermediates during RES complex assembly.
AB  - The action of the spliceosome depends on the stepwise cooperative assembly and
      disassembly of its components. Very strong cooperativity was observed for the RES
      (Retention and Splicing) hetero-trimeric complex where the affinity from binary
      to tertiary interactions changes more than 100-fold and affects RNA binding. The
      RES complex is involved in splicing regulation and retention of not properly
      spliced pre-mRNA with its three components--Snu17p, Pml1p and Bud13p--giving rise
      to the two possible intermediate dimeric complexes Pml1p-Snu17p and Bud13p
      Snu17p. Here we determined the three-dimensional structure and dynamics of the
      Pml1p-Snu17p and Bud13p-Snu17p dimers using liquid state NMR. We demonstrate that
      localized as well as global changes occur along the RES trimer assembly pathway.
      The stepwise rigidification of the Snu17p structure following the binding of
      Pml1p and Bud13p provides a basis for the strong cooperative nature of RES
      complex assembly.

PMID- 26212314
TI  - Utility of an appropriate reporter assay: Heliotrine interferes with
      GAL4/upstream activation sequence-driven reporter gene systems.
AB  - Reporter gene assays are widely used for the assessment of transcription factor
      activation following xenobiotic exposure of cells. A critical issue with such
      assays is the possibility of interference of test compounds with the test system,
      for example, by direct inhibition of the reporter enzyme. Here we show that the
      pyrrolizidine alkaloid heliotrine interferes with reporter signals derived from
      GAL4-based nuclear receptor transactivation assays by a mechanism independent of
      luciferase enzyme inhibition. These data highlight the necessity to conduct
      proper control experiments in order to avoid perturbation of reporter assays by
      test chemicals. 

PMID- 26212313
TI  - Vaccination of adolescents with chronic medical conditions: Special
      considerations and strategies for enhancing uptake.
AB  - Adolescents with chronic medical conditions (CMCs), a growing population
      worldwide, possess a wide array of preventive health care needs. Vaccination is
      strongly recommended for the vast majority of these adolescents given their
      increased risk of vaccine preventable infection and associated complications. Not
      only should they receive routine vaccines, but some also require additional
      vaccines. Despite these guidelines, evidence suggests that adolescents with CMCs
      often fail to receive needed vaccines. Many factors contribute to this under
      immunization, including lack of knowledge among parents and providers and
      suboptimal coordination of primary and subspecialty care. This review describes
      current vaccination recommendations for these adolescents as well as recent data
      related to infection risk, vaccine efficacy and safety, vaccination coverage, and
      the unique multilevel factors impacting uptake in this population. It also
      discusses strategies for improving coverage levels and reducing missed
      vaccination opportunities, with a particular focus on technology-based
      interventions. 

PMID- 26212315
TI  - Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to
      STXBP1 mutation.
AB  - BACKGROUND: Syntaxin Binding Protein 1 (STXBP1) mutations determine a central
      neurotransmission dysfunction through impairment of the synaptic vesicle release,
      thus causing a spectrum of phenotypes varying from syndromic and non-syndromic
      epilepsy to intellectual disability of variable degree. Among the antiepileptic
      drugs, levetiracetam has a unique mechanism of action binding SV2A, a
      glycoprotein of the synaptic vesicle release machinery. PATIENT DESCRIPTION: We
      report a 1-month-old boy manifesting an epileptic encephalopathy with clonic
      seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a
      dramatic response to levetiracetam with full epilepsy control and EEG
      normalization. Genetic analysis identified a novel de novo heterozygous mutation
      (c.[922A>T]p.[Lys308(*)]) in the STXBP1 gene that severely affects the protein.
      CONCLUSIONS: The observation of a dramatic efficacy of levetiracetam in a case of
      STXBP1 epileptic encephalopathy refractory to other antiepileptic drugs and
      considerations regarding the specific mechanism of action of levetiracetam
      modulating the same system affected by STXBP1 mutations support the hypothesis
      that this drug may be able to reverse specifically the disease epileptogenic
      abnormalities. Further clinical observations and laboratory studies are needed to
      confirm this hypothesis and eventually lead to consider levetiracetam as the
      first choice treatment of patients with suspected or confirmed STXBP1-related
      epilepsies.

PMID- 26212316
TI  - Calcium manganite as oxygen electrode materials for reversible solid oxide fuel
      cell.
AB  - For an efficient high-temperature reversible solid oxide fuel cell (RSOFC), the
      oxygen electrode should be highly active for the conversion between oxygen anions
      and oxygen gas. CaMnO(3-delta) (CM) is a perovskite that can be readily reduced
      with the formation of Mn(3+) giving rise to oxygen defective phases. CM is
      examined here as the oxygen electrode for a RSOFC. CaMn(0.9)Nb(0.1)O(3-delta)
      (CMN) with Nb doping shows superior electric conductivity (125 S cm(-1) at 700 
      degrees C) compared with CM (1-5 S cm(-1) at 700  degrees C) in air which is also
      examined for comparison. X-ray diffraction (XRD) data show that CM and CMN are
      compatible with the widely used yttria-stabilized zirconia (YSZ) electrolyte up
      to 950  degrees C. Both materials show a thermal expansion coefficient (TEC)
      close to 10.8-10.9 ppm K(-1) in the temperature range between 100-750  degrees C,
      compatible with that of YSZ. Polarization curves and electrochemical impedance
      spectra for both fuel cell and steam electrolysis modes were investigated at 700 
      degrees C, showing that CM presented a polarization resistance of 0.059 Omega
      cm(2) under a cathodic bias of -0.4 V while CMN gave a polarization resistance of
      0.081 Omega cm(2) under an anodic bias of 0.4 V. The phase stability up to 900 
      degrees C of these materials was investigated with thermogravimetric analysis
      (TGA) and variable temperature XRD.

PMID- 26212317
TI  - Knowledge of HPV and HPV Vaccine among Women Ages 19 to 26.
AB  - OBJECTIVE: To describe knowledge about human papillomavirus (HPV) and HPV
      vaccination among women ages 19 to 26 seeking a variety of services at
      reproductive health centers. A secondary objective was to identify common sources
      of HPV information. METHODS: Ten reproductive health centers enrolled 365 women
      ages 19 to 26 in a randomized, controlled trial to determine the effect of
      automated reminder messages on HPV vaccine completion. Using responses from a 61
      item self-administered baseline questionnaire completed before initiating the HPV
      vaccine, this subanalysis assessed participants' knowledge regarding HPV and the
      HPV vaccine. RESULTS: Knowledge of HPV prevention, transmission, and disease
      outcomes among the study population was highly variable. The mean HPV knowledge
      score was 11.0 of a possible 19 (SD = 3.8). Most participants (77%) had heard of
      the HPV vaccine before completing the questionnaire and indicated that their
      primary sources of information about the vaccine were television ads (61%),
      health care providers (52%), and friends (45%). CONCLUSIONS: Despite a relatively
      high awareness of the vaccine, specific knowledge regarding HPV and the HPV
      vaccine varied substantially and participant scores highlighted knowledge gaps
      among vaccine-eligible young women. Media, health care providers, and friends
      were identified by participants as sources of information and may influence their
      knowledge of HPV and the HPV vaccine.

PMID- 26212318
TI  - Barriers to Receiving Long-acting Reversible Contraception in the Postpartum
      Period.
AB  - OBJECTIVE: To assess why postpartum women who desired long-acting reversible
      contraception (LARC) did not receive it in the postpartum period and to assess
      which contraceptive methods they were using instead. STUDY DESIGN: This was a
      subgroup analysis of 324 women enrolled in a randomized, controlled trial to
      receive or not receive an educational LARC script during their postpartum
      hospitalization. Participants in this subgroup analysis stated that they were
      either using LARC (n = 114) or interested in using LARC (n = 210) during a follow
      up survey completed after their scheduled 6-week postpartum visit. Modified
      Poisson regression analysis was used to assess for characteristics associated
      with using LARC by the time of the follow-up survey. RESULTS: Women who were
      interested in LARC but not using it were more likely to be multiparous (relative
      risk [RR], 1.59; 95% CI, 1.19-2.11) and to have missed their postpartum visit
      (RR, 25.88; 95% CI, 3.75-178.44) compared with those using LARC. Among the
      interested 210 who were not using LARC, the most common reasons provided for non
      use were that they were told to come back for another insertion visit (45%),
      missed the postpartum visit (26%), and could not afford LARC (11%). The most
      common contraceptive methods used instead of LARC were barrier methods (42%) and
      abstinence (19%); 18% used no contraceptive method. CONCLUSION: Two-thirds (65%)
      of postpartum women who desired to use LARC did not receive it in the postpartum
      period and used less effective contraceptive methods. Increasing access to
      immediate postpartum LARC and eliminating two-visit protocols for LARC insertion
      may increase postpartum LARC use. As the Affordable Care Act moves toward full
      implementation, it is necessary to understand the barriers that prevent
      interested patients from receiving LARC.

PMID- 26212319
TI  - Replication-Coupled PCNA Unloading by the Elg1 Complex Occurs Genome-wide and
      Requires Okazaki Fragment Ligation.
AB  - The sliding clamp PCNA is a crucial component of the DNA replication machinery.
      Timely PCNA loading and unloading are central for genome integrity and must be
      strictly coordinated with other DNA processing steps during replication. Here, we
      show that the S. cerevisiae Elg1 replication factor C-like complex (Elg1-RLC)
      unloads PCNA genome-wide following Okazaki fragment ligation. In the absence of
      Elg1, PCNA is retained on chromosomes in the wake of replication forks, rather
      than at specific sites. Degradation of the Okazaki fragment ligase Cdc9 leads to
      PCNA accumulation on chromatin, similar to the accumulation caused by lack of
      Elg1. We demonstrate that Okazaki fragment ligation is the critical prerequisite
      for PCNA unloading, since Chlorella virus DNA ligase can substitute for Cdc9 in
      yeast and simultaneously promotes PCNA unloading. Our results suggest that Elg1
      RLC acts as a general PCNA unloader and is dependent upon DNA ligation during
      chromosome replication.

PMID- 26212320
TI  - A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy
      Stress.
AB  - SUMOylation has been implicated in cellular stress adaptation, but its role in
      regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor
      AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress
      triggers an increase in SUMO1 modification of LKB1, despite a global reduction in
      both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of
      LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO
      interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant
      had defective AMPK signaling and mitochondrial function, inducing death in energy
      deprived cells. These results provide additional insight into how LKB1-AMPK
      signaling is regulated during energy stress, and they highlight the critical role
      of SUMOylation in maintaining the cell's energy equilibrium. 

PMID- 26212321
TI  - RA Acts in a Coherent Feed-Forward Mechanism with Tbx5 to Control Limb Bud
      Induction and Initiation.
AB  - The retinoic acid (RA)- and beta-catenin-signaling pathways regulate limb bud
      induction and initiation; however, their mechanisms of action are not understood
      and have been disputed. We demonstrate that both pathways are essential and that
      RA and beta-catenin/TCF/LEF signaling act cooperatively with Hox gene inputs to
      directly regulate Tbx5 expression. Furthermore, in contrast to previous models,
      we show that Tbx5 and Tbx4 expression in forelimb and hindlimb, respectively, are
      not sufficient for limb outgrowth and that input from RA is required.
      Collectively, our data indicate that RA signaling and Tbx genes act in a coherent
      feed-forward loop to regulate Fgf10 expression and, as a result, establish a
      positive feedback loop of FGF signaling between the limb mesenchyme and ectoderm.
      Our results incorporate RA-, beta-catenin/TCF/LEF-, and FGF-signaling pathways
      into a regulatory network acting to recruit cells of the embryo flank to become
      limb precursors. 

PMID- 26212322
TI  - miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure,
      and Embryonic Viability.
AB  - The evolutionarily conserved miR-302 family of microRNAs is expressed during
      early mammalian embryonic development. Here, we report that deletion of miR-302a
      d in mice results in a fully penetrant late embryonic lethal phenotype. Knockout
      embryos have an anterior neural tube closure defect associated with a thickened
      neuroepithelium. The neuroepithelium shows increased progenitor proliferation,
      decreased cell death, and precocious neuronal differentiation. mRNA profiling at
      multiple time points during neurulation uncovers a complex pattern of changing
      targets over time. Overexpression of one of these targets, Fgf15, in the
      neuroepithelium of the chick embryo induces precocious neuronal differentiation.
      Compound mutants between mir-302 and the related mir-290 locus have a synthetic
      lethal phenotype prior to neurulation. Our results show that mir-302 helps
      regulate neurulation by suppressing neural progenitor expansion and precocious
      differentiation. Furthermore, these results uncover redundant roles for mir-290
      and mir-302 early in development.

PMID- 26212324
TI  - Dynamics of Tumor Heterogeneity Derived from Clonal Karyotypic Evolution.
AB  - Numerical chromosomal instability is a ubiquitous feature of human neoplasms. Due
      to experimental limitations, fundamental characteristics of karyotypic changes in
      cancer are poorly understood. Using an experimentally inspired stochastic model,
      based on the potency and chromosomal distribution of oncogenes and tumor
      suppressor genes, we show that cancer cells have evolved to exist within a narrow
      range of chromosome missegregation rates that optimizes phenotypic heterogeneity
      and clonal survival. Departure from this range reduces clonal fitness and limits
      subclonal diversity. Mapping of the aneuploid fitness landscape reveals a highly
      favorable, commonly observed, near-triploid state onto which evolving diploid-
      and tetraploid-derived populations spontaneously converge, albeit at a much lower
      fitness cost for the latter. Finally, by analyzing 1,368 chromosomal
      translocation events in five human cancers, we find that karyotypic evolution
      also shapes chromosomal translocation patterns by selecting for more oncogenic
      derivative chromosomes. Thus, chromosomal instability can generate the
      heterogeneity required for Darwinian tumor evolution. 

PMID- 26212323
TI  - Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a
      Host Factor for Hepatitis C Virus Entry.
AB  - Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism
      involving, among other host proteins, the virus receptor CD81. How CD81 governs
      HCV entry is poorly characterized, and CD81 protein interactions after virus
      binding remain elusive. We have developed a quantitative proteomics protocol to
      identify HCV-triggered CD81 interactions and found 26 dynamic binding partners.
      At least six of these proteins promote HCV infection, as indicated by RNAi. We
      further characterized serum response factor binding protein 1 (SRFBP1), which is
      recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells
      and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all
      seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus.
      Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results
      demonstrate the use of quantitative proteomics to elucidate pathogen entry and
      underscore the importance of host protein-protein interactions during HCV
      invasion. 

PMID- 26212326
TI  - How Does the Xenopus laevis Embryonic Cell Cycle Avoid Spatial Chaos?
AB  - Theoretical studies have shown that a deterministic biochemical oscillator can
      become chaotic when operating over a sufficiently large volume and have suggested
      that the Xenopus laevis cell cycle oscillator operates close to such a chaotic
      regime. To experimentally test this hypothesis, we decreased the speed of the
      post-fertilization calcium wave, which had been predicted to generate chaos.
      However, cell divisions were found to develop normally, and eggs developed into
      normal tadpoles. Motivated by these experiments, we carried out modeling studies
      to understand the prerequisites for the predicted spatial chaos. We showed that
      this type of spatial chaos requires oscillatory reaction dynamics with short
      pulse duration and postulated that the mitotic exit in Xenopus laevis is likely
      slow enough to avoid chaos. In systems with shorter pulses, chaos may be an
      important hazard, as in cardiac arrhythmias, or a useful feature, as in the
      pigmentation of certain mollusk shells. 

PMID- 26212325
TI  - Metabolic Interplay between Astrocytes and Neurons Regulates Endocannabinoid
      Action.
AB  - The endocannabinoid 2-arachidonoylglycerol (2-AG) is a retrograde lipid messenger
      that modulates synaptic function, neurophysiology, and behavior. 2-AG signaling
      is terminated by enzymatic hydrolysis-a reaction that is principally performed by
      monoacylglycerol lipase (MAGL). MAGL is broadly expressed throughout the nervous
      system, and the contributions of different brain cell types to the regulation of
      2-AG activity in vivo remain poorly understood. Here, we genetically dissect the
      cellular anatomy of MAGL-mediated 2-AG metabolism in the brain and show that
      neurons and astrocytes coordinately regulate 2-AG content and endocannabinoid
      dependent forms of synaptic plasticity and behavior. We also find that astrocytic
      MAGL is mainly responsible for converting 2-AG to neuroinflammatory
      prostaglandins via a mechanism that may involve transcellular shuttling of lipid
      substrates. Astrocytic-neuronal interplay thus provides distributed oversight of
      2-AG metabolism and function and, through doing so, protects the nervous system
      from excessive CB1 receptor activation and promotes endocannabinoid crosstalk
      with other lipid transmitter systems. 

PMID- 26212327
TI  - Neurolastin, a Dynamin Family GTPase, Regulates Excitatory Synapses and Spine
      Density.
AB  - Membrane trafficking and spinogenesis contribute significantly to changes in
      synaptic strength during development and in various paradigms of synaptic
      plasticity. GTPases of the dynamin family are key players regulating membrane
      trafficking. Here, we identify a brain-specific dynamin family GTPase,
      neurolastin (RNF112/Znf179), with closest homology to atlastin. We demonstrate
      that neurolastin has functional GTPase and RING domains, making it a unique
      protein identified with this multi-enzymatic domain organization. We also show
      that neurolastin is a peripheral membrane protein that localizes to endosomes and
      affects endosomal membrane dynamics via its RING domain. In addition, neurolastin
      knockout mice have fewer dendritic spines, and rescue of the wild-type phenotype
      requires both the GTPase and RING domains. Furthermore, we find fewer functional
      synapses and reduced paired pulse facilitation in neurolastin knockout mice.
      Thus, we identify neurolastin as a dynamin family GTPase that affects endosome
      size and spine density. 

PMID- 26212328
TI  - Chronic FLT3-ITD Signaling in Acute Myeloid Leukemia Is Connected to a Specific
      Chromatin Signature.
AB  - Acute myeloid leukemia (AML) is characterized by recurrent mutations that affect
      the epigenetic regulatory machinery and signaling molecules, leading to a block
      in hematopoietic differentiation. Constitutive signaling from mutated growth
      factor receptors is a major driver of leukemic growth, but how aberrant signaling
      affects the epigenome in AML is less understood. Furthermore, AML cells undergo
      extensive clonal evolution, and the mutations in signaling genes are often
      secondary events. To elucidate how chronic growth factor signaling alters the
      transcriptional network in AML, we performed a system-wide multi-omics study of
      primary cells from patients suffering from AML with internal tandem duplications
      in the FLT3 transmembrane domain (FLT3-ITD). This strategy revealed cooperation
      between the MAP kinase (MAPK) inducible transcription factor AP-1 and RUNX1 as a
      major driver of a common, FLT3-ITD-specific gene expression and chromatin
      signature, demonstrating a major impact of MAPK signaling pathways in shaping the
      epigenome of FLT3-ITD AML. 

PMID- 26212329
TI  - Structural Studies Reveal the Functional Modularity of the Scc2-Scc4 Cohesin
      Loader.
AB  - The remarkable accuracy of eukaryotic cell division is partly maintained by the
      cohesin complex acting as a molecular glue to prevent premature sister chromatid
      separation. The loading of cohesin onto chromosomes is catalyzed by the Scc2-Scc4
      loader complex. Here, we report the crystal structure of Scc4 bound to the N
      terminus of Scc2 and show that Scc4 is a tetratricopeptide repeat (TPR)
      superhelix. The Scc2 N terminus adopts an extended conformation and is entrapped
      by the core of the Scc4 superhelix. Electron microscopy (EM) analysis reveals
      that the Scc2-Scc4 loader complex comprises three domains: a head, body, and
      hook. Deletion studies unambiguously assign the Scc2N-Scc4 as the globular head
      domain, whereas in vitro cohesin loading assays show that the central body and
      the hook domains are sufficient to catalyze cohesin loading onto circular DNA,
      but not chromatinized DNA in vivo, suggesting a possible role for Scc4 as a
      chromatin adaptor.

PMID- 26212330
TI  - RNASEK Is a V-ATPase-Associated Factor Required for Endocytosis and the
      Replication of Rhinovirus, Influenza A Virus, and Dengue Virus.
AB  - Human rhinovirus (HRV) causes upper respiratory infections and asthma
      exacerbations. We screened multiple orthologous RNAi reagents and identified host
      proteins that modulate HRV replication. Here, we show that RNASEK, a
      transmembrane protein, was needed for the replication of HRV, influenza A virus,
      and dengue virus. RNASEK localizes to the cell surface and endosomal pathway and
      closely associates with the vacuolar ATPase (V-ATPase) proton pump. RNASEK is
      required for endocytosis, and its depletion produces enlarged clathrin-coated
      pits (CCPs) at the cell surface. These enlarged CCPs contain endocytic cargo and
      are bound by the scissioning GTPase, DNM2. Loss of RNASEK alters the localization
      of multiple V-ATPase subunits and lowers the levels of the ATP6AP1 subunit.
      Together, our results show that RNASEK closely associates with the V-ATPase and
      is required for its function; its loss prevents the early events of endocytosis
      and the replication of multiple pathogenic viruses. 

PMID- 26212331
TI  - Role of Prelimbic GABAergic Circuits in Sensory and Emotional Aspects of
      Neuropathic Pain.
AB  - Noxious stimuli are detected by peripheral nociceptors and then transmitted to
      higher CNS centers, where they are perceived as an unpleasant sensation. The
      mechanisms that govern the emotional component associated with pain are still
      incompletely understood. Here, we used optogenetic approaches both in vitro and
      in vivo to address this issue. We found that peripheral nerve injury inhibits
      pyramidal cell firing in the prelimbic area of the prefrontal cortex as a result
      of feed-forward inhibition mediated by parvalbumin-expressing GABAergic
      interneurons. In addition, activation of inhibitory archaerhodopsin or excitatory
      channelrhodopsin-2 in these neurons decreased and increased pain responses,
      respectively, in freely moving mice and accordingly modulated conditioned place
      preference scores and place escape/avoidance behavior. Our findings thus
      demonstrate an important role of the prelimbic area in sensory and emotional
      aspects of pain and identify GABAergic circuits in this region as a potential
      target for pain therapeutics.

PMID- 26212332
TI  - RING Dimerization Links Higher-Order Assembly of TRIM5alpha to Synthesis of K63
      Linked Polyubiquitin.
AB  - Members of the tripartite motif (TRIM) protein family of RING E3 ubiquitin (Ub)
      ligases promote innate immune responses by catalyzing synthesis of polyubiquitin
      chains linked through lysine 63 (K63). Here, we investigate the mechanism by
      which the TRIM5alpha retroviral restriction factor activates Ubc13, the K63
      linkage-specific E2. Structural, biochemical, and functional characterization of
      the TRIM5alpha:Ubc13-Ub interactions reveals that activation of the Ubc13-Ub
      conjugate requires dimerization of the TRIM5alpha RING domain. Our data explain
      how higher-order oligomerization of TRIM5alpha, which is promoted by the
      interaction with the retroviral capsid, enhances the E3 Ub ligase activity of
      TRIM5alpha and contributes to its antiretroviral function. This E3 mechanism, in
      which RING dimerization is transient and depends on the interaction of the TRIM
      protein with the ligand, is likely to be conserved in many members of the TRIM
      family and may have evolved to facilitate recognition of repetitive epitope
      patterns associated with infection.

PMID- 26212333
TI  - LMTK3 Represses Tumor Suppressor-like Genes through Chromatin Remodeling in
      Breast Cancer.
AB  - LMTK3 is an oncogenic receptor tyrosine kinase (RTK) implicated in various types
      of cancer, including breast, lung, gastric, and colorectal cancer. It is
      localized in different cellular compartments, but its nuclear function has not
      been investigated so far. We mapped LMTK3 binding across the genome using ChIP
      seq and found that LMTK3 binding events are correlated with repressive chromatin
      markers. We further identified KRAB-associated protein 1 (KAP1) as a binding
      partner of LMTK3. The LMTK3/KAP1 interaction is stabilized by PP1alpha, which
      suppresses KAP1 phosphorylation specifically at LMTK3-associated chromatin
      regions, inducing chromatin condensation and resulting in transcriptional
      repression of LMTK3-bound tumor suppressor-like genes. Furthermore, LMTK3
      functions at distal regions in tethering the chromatin to the nuclear periphery,
      resulting in H3K9me3 modification and gene silencing. In summary, we propose a
      model where a scaffolding function of nuclear LMTK3 promotes cancer progression
      through chromatin remodeling.

PMID- 26212334
TI  - Endogenous Glucagon-like Peptide-1 Suppresses High-Fat Food Intake by Reducing
      Synaptic Drive onto Mesolimbic Dopamine Neurons.
AB  - Glucagon-like peptide-1 (GLP-1) and its analogs act as appetite suppressants and
      have been proven to be clinically efficacious in reducing body weight in obese
      individuals. Central GLP-1 is expressed in a small population of brainstem cells
      located in the nucleus tractus solitarius (NTS), which project to a wide range of
      brain areas. However, it remains unclear how endogenous GLP-1 released in the
      brain contributes to appetite regulation. Using chemogenetic tools, we discovered
      that central GLP-1 acts on the midbrain ventral tegmental area (VTA) and
      suppresses high-fat food intake. We used integrated pathway tracing and synaptic
      physiology to further demonstrate that activation of GLP-1 receptors specifically
      reduces the excitatory synaptic strength of dopamine (DA) neurons within the VTA
      that project to the nucleus accumbens (NAc) medial shell. These data suggest that
      GLP-1 released from NTS neurons can reduce highly palatable food intake by
      suppressing mesolimbic DA signaling. 

PMID- 26212335
TI  - Comparison of Nanocarbon-Silicon Solar Cells with Nanotube-Si or Graphene-Si
      Contact.
AB  - Nanocarbon structures such as carbon nanotubes (CNTs) and graphene (G) have been
      combined with crystalline silicon wafers to fabricate nanocarbon-Si solar cells.
      Here, we show that the contact between the nanocarbon and Si plays an important
      role in the solar cell performance. An asymmetrically configured CNT-G composite
      film was used to create either CNT-Si dominating or G-Si dominating junctions,
      resulting in obviously different solar cell behavior in pristine state.
      Typically, solar cells with direct G-Si contacts (versus CNT-Si) exhibit better
      characteristics due to improved junction quality and larger contact area. On the
      basis of the composite film, the obtained CNT-G-Si solar cells reach power
      conversion efficiencies of 14.88% under air mass 1.5, 88 mW/cm2 illumination
      through established techniques such as acid doping and colloidal antireflection.
      Engineering the nanocarbon-Si contact is therefore a possible route for further
      improving the performance of this type of solar cells.

PMID- 26212339
TI  - Gene expression profiling of archived dried blood spot samples from the Danish
      Neonatal Screening Biobank.
AB  - A large part of the human genome is transcribed into various forms of RNA, and
      the global gene expression profile (GEP) has been studied for several years using
      technology such as RNA-microarrays. In this study, we evaluate whether neonatal
      dried blood spot (DBS) samples stored in the Danish Neonatal Screening Biobank
      (DNSB) can be used for GEP. This paper is divided into sub-studies examining the
      effects of: 1) different whole transcriptome amplification kits (WTA); 2) years
      of storage and storage in room temperature (RT) versus freezers (-20 degrees C)
      on DNSB DBS samples; 3) effects of RT storage vs freezer storage on DBS samples
      from the USA and DNSB, and 4) using smaller disc sizes, thereby decreasing DBS
      use. We present evidence that reliable and reproducible GEPs can be obtained
      using neonatal DBS samples. The main source of variation is the storage
      condition. When samples are stored at -20 degrees C, the dynamic range is
      increased, and Pearson correlations are higher. Differential analysis reveals no
      statistically significant differences between samples collected a decade apart
      and stored at -20 degrees C. However, samples stored at RT show differential
      expression for a third of the gene-specific probes. Our data also suggests that
      using alternate WTA kits significantly changes the GEP. Finally, the amount of
      input material, i.e., the size and number of DBS discs used, can be reduced to
      preserve this valuable and limited material. We conclude that DNSB DBS samples
      provide a reproducible resource for GEP. Results are improved if the cards are
      stored at -20 degrees C. Furthermore, it is important to use a single type of kit
      for analysis because using alternate kits introduces differential expression. 

PMID- 26212336
TI  - MitoRCA-seq reveals unbalanced cytocine to thymine transition in Polg mutant
      mice.
AB  - Mutations in mitochondrial DNA (mtDNA) can lead to a wide range of human
      diseases. We have developed a deep sequencing strategy, mitoRCA-seq, to detect
      low-frequency mtDNA point mutations starting with as little as 1 ng of total DNA.
      It employs rolling circle amplification, which enriches the full-length circular
      mtDNA by either custom mtDNA-specific primers or a commercial kit, and minimizes
      the contamination of nuclear encoded mitochondrial DNA (Numts). By analyzing the
      mutation profiles of wild-type and Polg (mitochondrial DNA polymerase gamma)
      mutant mice, we found that mice with the proofreading deficient mtDNA polymerase
      have a significantly higher mutation load by expanding the number of mutation
      sites and to a lesser extent by elevating the mutation frequency at existing
      sites even before the premature aging phenotypes appear. Strikingly, cytocine (C)
      to thymine (T) transitions are found to be overrepresented in the mtDNA of Polg
      mutated mice. The C -> T transition, compared to other types of mutations, tends
      to increase the hydrophobicity of the underlying amino acids, and may contribute
      to the impaired protein function of the Polg mutant mice. Taken together, our
      findings may provide clues to further investigate the molecular mechanism
      underlying premature aging phenotype in Polg mutant mice. 

PMID- 26212340
TI  - Biotransformation of tetrabromobisphenol A (TBBPA) in anaerobic digester sludge,
      soils, and freshwater sediments.
AB  - The biotransformation of tetrabromobisphenol A (TBBPA) was evaluated in anaerobic
      digester sludge, soils, and freshwater sediments. In anaerobic digester sludge,
      TBBPA biotransformed rapidly with a 50% disappearance time (DT50) of 19 days,
      though little mineralization (1.1%) was observed. In aerobic soils,
      mineralization of TBBPA ranged from 17.5% to 21.6% with 55.3-83.6% of the TBBPA
      incorporated into the soils as a non-extractable bound residue. The DT50 for
      TBBPA in aerobic soils ranged from 5.3 to 7.7 days. In anaerobic soils, 48.3-100%
      of the TBBPA was incorporated into the soils as non-extractable bound residue
      with <4% mineralized. The soil fate studies demonstrated extensive incorporation
      of TBBPA into the solid matrix and this association was related to the amount of
      organic carbon in the soils (i.e., greater association of TBBPA with soil at
      higher organic carbon content). In anaerobic sediments the DT50 for TBBPA ranged
      from 28 to 42 days, whereas in aerobic sediments the DT50 for TBBPA ranged from
      48 to 84 days and depended on the initial dose concentration. Most of the TBBPA
      in the sediment studies was incorporated as a non-extractable bound residue with
      little mineralization observed. Sediment extracts revealed three unknown
      biotransformation products and bisphenol A (BPA). These results were consistent
      with previously published studies where TBBPA biotransformed in anaerobic
      environments (digester sludge and sediments) by debromination and slowly
      mineralized in the test environments (anaerobic digester sludge, soils, and
      freshwater sediments). 

PMID- 26212341
TI  - Decreased CXCL12 is associated with impaired alveolar epithelial cell migration
      and poor lung healing after lung resection.
AB  - BACKGROUND: Prolonged air leak (PAL) is an important cause of morbidity and
      mortality after lung resection, but its pathogenesis has not been elucidated.
      Migration of alveolar type II epithelial cells is essential for lung wound
      repair. Here we determined the role of C-X-C motif chemokine 12 (CXCL12) on
      alveolar epithelial cell migration and lung wound healing. METHODS: CXCL12 in the
      pleural fluid of patients was analyzed using enzyme-linked immunosorbent assay.
      Human A549 and murine MLE12 alveolar epithelial cell lines were used for wound
      closure, cell migration, and proliferation assays. Western blot was used to
      analyze Rac1 and cofilin. RESULTS: Pleural CXCL12 was decreased in patients with
      PAL (1,389 +/- 192 vs 3,270 +/- 247 pg/mL; P < .0001). CXCL12 enhanced scratch
      wound closure in both A549 (77.9 +/- 0.7% vs 71.5 +/- 0.4%; P = .0016) and MLE12
      (92.9 +/- 4.9% vs 66.0 +/- 4.8%; P = .017). CXCL12 enhanced migration by 57% in
      A549 (P = .0008) and by 86% in MLE12 (P < .0001). AMD3100, a selective CXCR4
      antagonist, prevented the effects of CXCL12. CXCL12 increased Rac1 and cofilin
      activation but did not change bromodeoxyuridine incorporation or cell counts.
      CONCLUSION: Reduced pleural CXCL12 is associated with PAL. CXCL12 promotes
      alveolar epithelial cell migration by binding to its receptor CXCR4 and may have
      a role in lung healing. CXCL12-mediated alveolar epithelial cell migration is
      associated with Rac1 and cofilin activation.

PMID- 26212344
TI  - The utility of peripheral thyrotropin receptor mRNA in the management of
      differentiated thyroid cancer.
AB  - BACKGROUND: Our aim was to analyze the utility of peripheral thyrotropin receptor
      (TSHR) messenger RNA (mRNA) in predicting and detecting the recurrence of
      differentiated thyroid cancer. METHODS: Peripheral blood TSHR-mRNA was obtained
      in 103 patients before and after total thyroidectomy. An analysis was performed
      to correlate peripheral blood TSHR-mRNA concentration with oncologic outcomes.
      RESULTS: Tumor types were papillary (n = 92), follicular (n = 9) and Hurthle cell
      (n = 2) cancer. Preoperative TSHR-mRNA was >=1.02 ng/MUg in 85% (88/103). On
      follow-up (median 48 months), 10 patients (10 %) developed recurrence. Recurrence
      rate in patients with a preoperative TSHR-mRNA >= 1.02 ng/MUg was 11% versus 0%
      in those with a lesser concentration. TSHR-mRNA correctly diagnosed 7 (70%) of 10
      recurrences. Of 19 patients with positive thyroglobulin (Tg) antibodies, TSHR
      mRNA confirmed disease-free status in 12 (63%) and recurrence in 1 (5%). For Tg,
      TSHR-mRNA and whole-body radioactive iodine scan, sensitivity was 70%, 70%, and
      75%; specificity 94%, 76%, 97%; PPV 54%, 24%, and 67%; and NPV 97%, 96%, and 98%,
      respectively, in detecting recurrent disease. CONCLUSION: This study shows that
      patients with preoperative TSHR-mRNA >=1.02 ng/MUg may be at a greater risk for
      recurrence compared with those with a lesser concentration. In the presence of Tg
      antibodies, TSHR-mRNA accurately predicted disease status in 68% of patients. Its
      overall performance in detecting recurrence was similar to Tg and whole-body
      radioactive iodine scan, albeit with lower specificity and PPV.

PMID- 26212345
TI  - Removal of steroid estrogens from municipal wastewater in a pilot scale expanded
      granular sludge blanket reactor and anaerobic membrane bioreactor.
AB  - Anaerobic treatment of municipal wastewater offers the prospect of a new paradigm
      by reducing aeration costs and minimizing sludge production. It has been
      successfully applied in warm climates, but does not always achieve the desired
      outcomes in temperate climates at the biochemical oxygen demand (BOD) values of
      municipal crude wastewater. Recently the concept of 'fortification' has been
      proposed to increase organic strength and has been demonstrated at the laboratory
      and pilot scale treating municipal wastewater at temperatures of 10-17 degrees C.
      The process treats a proportion of the flow anaerobically by combining it with
      primary sludge from the residual flow and then polishing it to a high effluent
      standard aerobically. Energy consumption is reduced as is sludge production.
      However, no new treatment process is viable if it only addresses the problems of
      traditional pollutants (suspended solids - SS, BOD, nitrogen - N and phosphorus -
      P); it must also treat hazardous substances. This study compared three potential
      municipal anaerobic treatment regimes, crude wastewater in an expanded granular
      sludge blanket (EGSB) reactor, fortified crude wastewater in an EGSB and crude
      wastewater in an anaerobic membrane bioreactor. The benefits of fortification
      were demonstrated for the removal of SS, BOD, N and P. These three systems were
      further challenged with the removal of steroid estrogens at environmental
      concentrations from natural indigenous sources. All three systems removed these
      compounds to a significant degree, confirming that estrogen removal is not
      restricted to highly aerobic autotrophs, or aerobic heterotrophs, but is also a
      faculty of anaerobic bacteria. 

PMID- 26212346
TI  - Fecal calprotectin is a clinically relevant biomarker of mucosal healing in
      patients with quiescent ulcerative colitis.
AB  - BACKGROUND AND AIM: Calprotectin is an abundant protein in neutrophils, which
      infiltrate the mucosa during inflammation. Fecal calprotectin (FC) level has
      shown correlation with disease activity in ulcerative colitis (UC) patients.
      Additionally, FC level is expected to indicate mucosal healing (MH). This study
      was to see the significance of FC for predicting MH in patients with quiescent
      UC. METHODS: A total of 112 patients with quiescent UC were included. After
      taking blood and stool samples, patients underwent total colonoscopy, and the
      Mayo endoscopic subscore was recorded. FC was measured by fluorescence enzyme
      immunoassay. C-reactive protein, hemoglobin, erythrocyte sedimentation rate, and
      serum albumin were measured as conventional biomarkers. MH was defined as Mayo 0
      or 0 and 1, and receiver-operator characteristic analyses were undertaken to
      determine the significance levels of measurements. RESULTS: Data from 105
      patients were available. Eleven patients showed Mayo >= 2. The median
      (interquartile range) of FC level of all patients was 115 ug/g (45.4-420). The
      area under the curve (AUC) in receiver operator characteristic analysis of FC to
      predict Mayo 0 and 1 was 0.869 with a cut-off value of 200 ug/g yielding 67%
      sensitivity and 91% specificity, which were the best among all biomarkers.
      However, the power of FC to predict Mayo 0 was modest; the AUC was 0.639 and cut
      off value 194 ug/g with 71% sensitivity and 58% specificity. CONCLUSIONS: Based
      on the findings of this study, we believe that FC is a clinically relevant
      biomarker of MH in patients with quiescent UC. Other favorable features of FC
      test include feasibility and non-invasiveness.

PMID- 26212347
TI  - Investigation of Serine-Proteinase-Catalyzed Peptide Splicing in Analogues of
      Sunflower Trypsin Inhibitor 1 (SFTI-1).
AB  - Serine-proteinase-catalyzed peptide splicing was demonstrated in analogues of the
      trypsin inhibitor SFTI-1: both single peptides and two-peptide chains (C- and N
      terminal peptide chains linked by a disulfide bridge). In the second series,
      peptide splicing with catalytic amount of proteinase was observed only when
      formation of acyl-enzyme intermediate was preceded by hydrolysis of the substrate
      Lys-Ser peptide bond. Here we demonstrate that with an equimolar amount of the
      proteinase, splicing occurs in all the two-peptide-chain analogues. This
      conclusion was supported by high resolution crystal structures of selected
      analogues in complex with trypsin. We showed that the process followed a direct
      transpeptidation mechanism. Thus, the acyl-enzyme intermediate was formed and was
      immediately used for a new peptide bond formation; products associated with the
      hydrolysis of the acyl-enzyme were not observed. The peptide splicing was
      sequence- not structure-specific. 

PMID- 26212348
TI  - Perceptual and affective mechanisms in facial expression recognition: An
      integrative review.
AB  - Facial expressions of emotion involve a physical component of morphological
      changes in a face and an affective component conveying information about the
      expresser's internal feelings. It remains unresolved how much recognition and
      discrimination of expressions rely on the perception of morphological patterns or
      the processing of affective content. This review of research on the role of
      visual and emotional factors in expression recognition reached three major
      conclusions. First, behavioral, neurophysiological, and computational measures
      indicate that basic expressions are reliably recognized and discriminated from
      one another, albeit the effect may be inflated by the use of prototypical
      expression stimuli and forced-choice responses. Second, affective content along
      the dimensions of valence and arousal is extracted early from facial expressions,
      although this coarse affective representation contributes minimally to
      categorical recognition of specific expressions. Third, the physical
      configuration and visual saliency of facial features contribute significantly to
      expression recognition, with "emotionless" computational models being able to
      reproduce some of the basic phenomena demonstrated in human observers. We
      conclude that facial expression recognition, as it has been investigated in
      conventional laboratory tasks, depends to a greater extent on perceptual than
      affective information and mechanisms.

PMID- 26212349
TI  - Rest Pain and Movement-Evoked Pain as Unique Constructs in Hip and Knee
      Replacements.
AB  - OBJECTIVE: There is limited information about the extent to which the association
      between preoperative and chronic postoperative pain is mediated via pain-on
      movement or pain-at-rest. We explored these associations in patients undergoing
      total hip replacement (THR) and total knee replacement (TKR). METHODS: A total of
      322 and 316 patients receiving THR and TKR, respectively, were recruited into a
      single-center UK cohort (Arthroplasty Pain Experience) study. Preoperative, acute
      postoperative, and 12-month pain severity was measured using self-reported pain
      instruments. The association between preoperative/acute pain and chronic
      postoperative pain was investigated using structural equation modeling (SEM).
      RESULTS: Patients with high levels of preoperative pain were more likely to
      report chronic pain after THR (beta = 0.195, P = 0.02) and TKR (beta = 0.749, P <
      0.0001). Acute postoperative pain-on-movement was not associated with chronic
      pain after TKR or THR after adjusting for preoperative pain; however, acute pain
      at-rest was associated with chronic pain after THR (beta = 0.20, P < 0.0002) but
      not TKR after adjusting for preoperative pain. Analysis of pain-at-rest and pain
      on-movement highlighted differences between THR and TKR patients. Chronic pain-at
      rest after THR was weakly associated with pain-at-rest during the preoperative
      (beta = 0.11, P = 0.068) and acute postoperative period (beta = 0.21, P <
      0.0001). In contrast, chronic pain-on-movement after TKR was strongly associated
      with the severity of pain-on-movement during the preoperative period (beta =
      0.51, P = 0.001). CONCLUSION: SEM illustrated the different patterns of
      association between measures of pain over time in patients undergoing THR and TKR
      for osteoarthritis. These findings highlight the importance of future work that
      explores the mechanisms underlying pain-on-movement and pain-at-rest.

PMID- 26212350
TI  - Epigenetic alterations in sperm associated with male infertility.
AB  - The most common form of male infertility is a low sperm count, known as
      oligozoospermia. Studies suggest that oligozoospermia is associated with
      epigenetic alterations. Epigenetic alterations in sperm, which may arise due to
      the exposure of gametes to environmental factors or those that pre-exist in the
      sperm of infertile individuals, may contribute to the increased incidence of
      normally rare imprinting disorders in babies conceived after assisted
      reproductive technology using the sperm of infertile men. Genomic imprinting is
      an important developmental process whereby the allelic activity of certain genes
      is regulated by DNA methylation established during gametogenesis. The aberrant
      expression of several imprinted genes has been linked to various diseases,
      malignant tumors, lifestyle and mental disorders in humans. Understanding how
      infertility and environmental factors such as reproductive toxicants, certain
      foods, and drug exposures during gametogenesis contribute to the origins of these
      disorders via defects in sperm is of paramount importance. In this review, we
      discuss the association of epigenetic alterations with abnormal spermatogenesis
      and the evidence that epigenetic processes, including those required for genomic
      imprinting, may be sensitive to environmental exposures during gametogenesis,
      fertilization and early embryonic development. In addition, we review imprinting
      diseases and their relationships with environmental factors. While the plasticity
      of epigenetic marks may make these more susceptible to modification by the
      environment, this also suggests that aberrant epigenetic marks may be reversible.
      A greater understanding of this process and the function of epidrugs may lead to
      the development of new treatment methods for many adult diseases in the future. 

PMID- 26212351
TI  - Dosimetric study of volumetric arc modulation with RapidArc and intensity
      modulated radiotherapy in patients with cervical cancer and comparison with 3
      dimensional conformal technique for definitive radiotherapy in patients with
      cervical cancer.
AB  - INTRODUCTION: For patients with cervical cancer, intensity-modulated radiation
      therapy (IMRT) improves target coverage and allows dose escalation while reducing
      the radiation dose to organs at risk (OARs). In this study, we compared
      dosimetric parameters among 3-dimensional conformal radiotherapy (3D-CRT), "step
      and-shoot" IMRT, and volumetric intensity-modulated arc radiotherapy (VMAT) in a
      series of patients with cervical cancer receiving definitive radiotherapy.
      Computed tomography (CT) scans of 10 patients with histologically proven cervical
      cancer treated with definitive radiation therapy (RT) from December 2008 to March
      2010 at our department were selected for this study. The gross tumor volume (GTV)
      and clinical target volume (CTV) were delineated following the guidelines of the
      Gyn IMRT consortium that included cervix, uterus, parametrial tissues, and the
      pelvic nodes including presacral. The median age was 57 years (range: 30 to 85
      years). All 10 patients had squamous cell carcinoma with Federation of Gynecology
      and Obstetrics (FIGO) stage IB-IIIB. All patients were treated by VMAT. OAR doses
      were significantly reduced for plans with intensity-modulated technique compared
      with 3D-CRT except for the dose to the vagina. Between the 2 intensity-modulated
      techniques, significant difference was observed for the mean dose to the small
      intestine, to the benefit of VMAT (p < 0.001). There was no improvement in terms
      of OARs sparing for VMAT although there was a tendency for a slightly decreased
      average dose to the rectum: - 0.65Gy but not significant (p = 0.07). The
      intensity modulation techniques have many advantages in terms of quality indexes,
      and particularly OAR sparing, compared with 3D-CRT. Following the ongoing
      technologic developments in modern radiotherapy, it is essential to evaluate the
      intensity-modulated techniques on prospective studies of a larger scale.

PMID- 26212352
TI  - Serrated tubulovillous adenoma of the large intestine.
AB  - AIMS: Most colorectal polyps are classified readily, but a subset of
      tubulovillous adenomas (TVA) with prominent serrated architecture causes
      diagnostic confusion. We aimed to (i) identify histological features that
      separate serrated TVAs from both conventional TVAs and traditional serrated
      adenomas (TSA) and (ii) perform a clinicopathological and molecular analysis to
      determine if the serrated TVA has unique features. METHODS AND RESULTS: We
      collected 48 serrated TVAs, 50 conventional TVAs and 66 BRAF wild-type TSAs for
      analysis. For each polyp we performed a clinicopathological assessment, BRAF and
      KRAS mutation profiling, cytosine-phosphate-guanosine (CpG) island methylator
      phenotype status, MGMT methylation and immunohistochemical assessment of seven
      markers [MutL homologue 1 (MLH1), p16, p53, beta-catenin, Ki67, CK7 and CK20]. We
      found that serrated TVAs can be diagnosed reliably, and have features distinct
      from both conventional TVAs and TSAs. Compared to conventional TVAs, serrated
      TVAs are larger, more often proximal, more histologically advanced, show more CpG
      island methylation and more frequent KRAS mutation. Compared to TSAs they are
      more often proximal, show less CpG island methylation, more frequent MGMT
      methylation and more frequent nuclear staining for beta-catenin. CONCLUSIONS: The
      serrated TVA can be diagnosed reliably and has unique features. It represents a
      precursor of KRAS mutated, microsatellite stable colorectal carcinoma.

PMID- 26212353
TI  - Tyrosinase inhibition kinetic studies of standardized extract of Berberis
      aristata.
AB  - The stem bark and wood of Berberis aristata DC (Daruharidra) are one of the
      principal ingredients of traditional skin lighting and exfoliating scrub
      preparation in India. The standardised extract of B. aristata was screened to
      evaluate their in vitro antityrosinase activity and inhibition kinetics.
      Phytochemical and pharmacological studies were carried out with different solvent
      fractions of the methanol extract of B. aristata (MEBA). RP-HPLC analysis was
      used to determine the berberine content in extract and fractions of B. aristata.
      MEBA showed maximum berberine content. Extract and fractions of B. aristata
      contain the maximum amount of alkaloids than other constituents. In tyrosinase
      inhibition assay, MEBA was found to possess highest dose-dependent monophenolase
      and moderate diphenolase activity. The enzyme kinetic study revealed that MEBA
      possessed mixed type inhibition of monophenolase activity of tyrosinase. These
      bioactivities indicate that the MEBA has antihyperpigmentation potential in human
      skin. 

PMID- 26212354
TI  - Kinetic Analysis of a Globin-Coupled Histidine Kinase, AfGcHK: Effects of the
      Heme Iron Complex, Response Regulator, and Metal Cations on Autophosphorylation
      Activity.
AB  - The globin-coupled histidine kinase, AfGcHK, is a part of the two-component
      signal transduction system from the soil bacterium Anaeromyxobacter sp. Fw109-5.
      Activation of its sensor domain significantly increases its autophosphorylation
      activity, which targets the His183 residue of its functional domain. The
      phosphate group of phosphorylated AfGcHK is then transferred to the cognate
      response regulator. We investigated the effects of selected variables on the
      autophosphorylation reaction's kinetics. The kcat values of the heme Fe(III)-OH(
      ), Fe(III)-cyanide, Fe(III)-imidazole, and Fe(II)-O2 bound active AfGcHK forms
      were 1.1-1.2 min(-1), and their Km(ATP) values were 18.9-35.4 MUM. However, the
      active form bearing a CO-bound Fe(II) heme had a kcat of 1.0 min(-1) but a very
      high Km(ATP) value of 357 MUM, suggesting that its active site structure differs
      strongly from the other active forms. The Fe(II) heme-bound inactive form had
      kcat and Km(ATP) values of 0.4 min(-1) and 78 MUM, respectively, suggesting that
      its low activity reflects a low affinity for ATP relative to that of the Fe(III)
      form. The heme-free form exhibited low activity, with kcat and Km(ATP) values of
      0.3 min(-1) and 33.6 MUM, respectively, suggesting that the heme iron complex is
      essential for high catalytic activity. Overall, our results indicate that the
      coordination and oxidation state of the sensor domain heme iron profoundly affect
      the enzyme's catalytic activity because they modulate its ATP binding affinity
      and thus change its kcat/Km(ATP) value. The effects of the response regulator and
      different divalent metal cations on the autophosphorylation reaction are also
      discussed. 

PMID- 26212355
TI  - Solution-processed white phosphorescent tandem organic light-emitting devices.
AB  - Solution-processed phosphorescent tandem organic light-emitting devices (OLEDs)
      exhibit extremely high efficiencies (94 cd A(-1) ) and 26% external quantum
      efficiency (EQE) at 5000 cd m(-2) for green phosphorescent devices and 69 cd A(
      1) and 28% EQE at 5000 cd m(-2) for white phosphorescent devices. Development of
      these highly efficient solution-processed tandem-OLEDs with inverted device
      structure paves the way to printable, low-cost, and large-area white lighting. 

PMID- 26212356
TI  - Room-temperature decarboxylative alkynylation of carboxylic acids using
      photoredox catalysis and EBX reagents.
AB  - Alkynes are used as building blocks in synthetic and medicinal chemistry,
      chemical biology, and materials science. Therefore, efficient methods for their
      synthesis are the subject of intensive research. Herein, we report the direct
      synthesis of alkynes from readily available carboxylic acids at room temperature
      under visible-light irradiation. The combination of an iridium photocatalyst with
      ethynylbenziodoxolone (EBX) reagents allowed the decarboxylative alkynylation of
      carboxylic acids in good yields under mild conditions. The method could be
      applied to silyl-, aryl-, and alkyl- substituted alkynes. It was particularly
      successful in the case of alpha-amino and alpha-oxo acids derived from biomass. 

PMID- 26212357
TI  - Downstairs gene flow: the effects of a linear sequence of waterfalls on the only
      population of the endangered minnow Astyanax xavante.
AB  - The aim of this study was to estimate the genetic diversity and structure of the
      only known population of minnow Astyanax xavante, which inhabits a stretch of
      river including several waterfalls. The FST values among the samples were not
      significant, except between two populations separated by a 30 m waterfall.
      Nevertheless, haplotype and nucleotide diversity increased in the downstream
      direction, indicating that gene flow is unidirectional, which indicates this
      genetic pattern as downstairs gene flow, as it has the effect of increasing
      genetic diversity in the downstream direction.

PMID- 26212358
TI  - Secondary haemophagocytic lymphohistiocytosis: Experience from the Uppsala
      University Hospital.
AB  - BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome
      characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple
      organ failure. HLH in adults is often secondary to autoimmune diseases, cancer,
      or infections in contrast to familial HLH. Treatment of secondary HLH is directed
      against the triggering disease in addition to immunosuppressive therapy, the
      latter commonly according to the HLH-2004 protocol. METHODS: We conducted a
      retrospective study to identify triggering diseases, disease-specific and
      immunosuppressive therapy administered, and prognosis in adult patients with
      secondary HLH. Patient data were collected from October 2010 to January 2015.
      RESULTS: Ten adult patients with secondary HLH were identified. Seven were men,
      and the median age at diagnosis was 62 years. Five cases were triggered by
      malignant disease and five by infection. The median patient fulfilled five of the
      eight HLH-2004 diagnostic criteria. All patients fulfilled the criteria fever,
      cytopenia, and ferritin >500 ug/L. Median time from hospital admission to HLH
      diagnosis was 20 days. Four patients received immunosuppressive therapy according
      to the HLH-2004 protocol. The prognosis was dismal, especially for the patients
      with malignancy-associated HLH, of whom all died. CONCLUSION: HLH should be
      suspected in patients who present with fever, cytopenia, and ferritin >500 ug/L.
      Secondary HLH has a dismal prognosis. None of the patients with HLH triggered by
      malignancy survived. Achieving remission of the triggering disease seems to be
      important for a favourable outcome as, in all surviving patients, the
      haemophagocytic syndrome resolved after remission of the underlying infection.

PMID- 26212359
TI  - Proinflammatory receptor switch from Galphas to Galphai signaling by beta
      arrestin-mediated PDE4 recruitment in mixed RA synovial cells.
AB  - OBJECTIVE: In chronic inflammation, prevention of cAMP degradation by
      phosphodiesterase-4 (PDE4) inhibition can be anti-inflammatory therapy. However,
      PDE4 inhibition was uneffective in rheumatoid arthritis (RA). Recent studies
      demonstrated that PDE4/beta-arrestin interaction at beta-adrenoceptors resulted
      in switching from Galphas to Galphai signaling and ERK1/2 activation. Such a
      switch in signaling might elicit proinflammatory effects. We aimed to investigate
      this possible Galphas to Galphai signaling switch in RA and osteoarthritis (OA)
      mixed synoviocytes. METHODS: Synoviocytes were treated alone or with combinations
      of adrenergic, dopaminergic, and adenosinergic drugs, rolipram (PDE4 inhibitor),
      inhibitors of Galphai signaling (pertussis toxin), and blockers of protein kinase
      A (PKA). Under normoxic or hypoxic conditions, proinflammatory TNF was the
      readout-parameter. We investigated co-expression and interaction of PDE4 and beta
      arrestin by imaging techniques. Expression of pERK1/2 was analyzed by western
      blotting. RESULTS: Mixed synoviocytes in RA and OA possessed all major Galphas
      coupled neurotransmitter receptors. Under hypoxia, particularly in RA cells,
      Galphas-coupled receptor agonists unexpectedly increased TNF and respective
      antagonists decreased TNF. Under hypoxia, rolipram alone or rolipram plus Galphas
      agonists increased TNF, which was reversed by pertussis toxin or PKA inhibition.
      Co-localization and interaction of PDE4 and beta-arrestin in synovial tissue and
      cells was demonstrated. Galphas agonists or rolipram plus Galphas agonists
      increased pERK1/2 expression. CONCLUSIONS: This study in human arthritic synovial
      tissue presents an unexpected proinflammatory switch from Galphas to Galphai
      signaling, which depends on PDE4/beta-arrestin interaction. This phenomenon is
      most probably responsible for reduced efficacy of PDE4 inhibitors and Galphas
      agonists in RA.

PMID- 26212361
TI  - Human cytomegalovirus miR-UL36-5p inhibits apoptosis via downregulation of
      adenine nucleotide translocator 3 in cultured cells.
AB  - Human cytomegalovirus (HCMV) encodes at least 26 microRNAs (miRNA). These miRNAs
      are utilized by HCMV to regulate its own genes as well as the genes of the host
      cell during infection. It has been reported that a cellular gene, solute carrier
      family 25, member 6 (SLC25A6), which is also designated adenine nucleotide
      translocator 3 (ANT3), was identified as a candidate target of hcmv-miR-UL36-5p
      by hybrid PCR. In this study, ANT3 was further demonstrated to be a direct target
      of hcmv-miR-UL36-5p by luciferase reporter assays. The expression level of ANT3
      protein was confirmed, by western blotting, to be directly downregulated by
      overexpression of hcmv-miR-UL36-5p in HEK293 cells, U373 cells and HELF cells.
      Moreover, HCMV-infected cells showed a decrease in the ANT3 protein level. Using
      ANT3-specific small interfering RNA (siRNA) and an inhibitor for hcmv-miR-UL36
      5p, it was shown that inhibition of apoptosis by hcmv-miR-UL36-5p in these cells
      specifically occurred via inhibition of ANT3 expression. These results imply that
      hcmv-miR-UL36-5 may play the same role during actual HCMV infection in order to
      establish a balance between the host cell and the virus. 

PMID- 26212360
TI  - Computational Classification Approach to Profile Neuron Subtypes from Brain
      Activity Mapping Data.
AB  - The analysis of cell type-specific activity patterns during behaviors is
      important for better understanding of how neural circuits generate cognition, but
      has not been well explored from in vivo neurophysiological datasets. Here, we
      describe a computational approach to uncover distinct cell subpopulations from in
      vivo neural spike datasets. This method, termed "inter-spike-interval
      classification-analysis" (ISICA), is comprised of four major steps: spike pattern
      feature-extraction, pre-clustering analysis, clustering classification, and
      unbiased classification-dimensionality selection. By using two key features of
      spike dynamic - namely, gamma distribution shape factors and a coefficient of
      variation of inter-spike interval - we show that this ISICA method provides
      invariant classification for dopaminergic neurons or CA1 pyramidal cell subtypes
      regardless of the brain states from which spike data were collected. Moreover, we
      show that these ISICA-classified neuron subtypes underlie distinct physiological
      functions. We demonstrate that the uncovered dopaminergic neuron subtypes encoded
      distinct aspects of fearful experiences such as valence or value, whereas
      distinct hippocampal CA1 pyramidal cells responded differentially to ketamine
      induced anesthesia. This ISICA method should be useful to better data mining of
      large-scale in vivo neural datasets, leading to novel insights into circuit
      dynamics associated with cognitions. 

PMID- 26212362
TI  - Molecular characterization of a reassortant H11N9 subtype avian influenza virus
      isolated from a domestic duck in Eastern China.
AB  - During surveillance for avian influenza viruses (AIVs) in live-poultry markets in
      Eastern China in 2013, an H11N9 AIV was isolated from a domestic duck.
      Phylogenetic analysis showed that this strain received its genes from H11, H3,
      H10, and H7 AIVs of poultry in China. This strain was found to be minimally
      pathogenic in mice and was able to replicate in mice without prior adaptation.
      Considering that the reassorted H11N9 viruses were isolated from domestic ducks
      in this study, it is possible that these ducks play an important role in the
      generation of novel reassorted H11 AIVs. 

PMID- 26212363
TI  - Complete genome sequence of trivittatus virus.
AB  - Trivittatus virus (family Bunyaviridae, genus Orthobunyavirus) represents an
      important genetic intermediate between the California encephalitis group and the
      Bwamba/Pongola and Nyando groups. Here, we report the first complete genome
      sequence of the prototype (Eklund) strain, isolated in 1948, which,
      interestingly, shows only a few differences when compared to partial sequences of
      modern strains. 

PMID- 26212364
TI  - Full genome analysis of bovine astrovirus from fecal samples of cattle in Japan:
      identification of possible interspecies transmission of bovine astrovirus.
AB  - A viral metagenomics approach was used to investigate fecal samples of Japanese
      calves with and without diarrhea. Of the different viral pathogens detected, read
      counts gave nearly complete astrovirus-related RNA sequences in 15 of the 146
      fecal samples collected in three distinct areas (Hokkaido, Ishikawa, and
      Kagoshima Prefectures) between 2009 and 2015. Due to the lack of genetic
      information about bovine astroviruses (BoAstVs) in Japan, these sequences were
      analyzed in this study. Nine of the 15 Japanese BoAstVs were closely related to
      Chinese BoAstVs and clustered into a lineage (tentatively named lineage 1) in all
      phylogenetic trees. Three of 15 strains were phylogenetically separate from
      lineage 1, showing low sequence identities, and clustered instead with an
      American strain isolated from cattle with respiratory disease (tentatively named
      lineage 2). Interestingly, two of 15 strains clustered with lineage 1 in the open
      reading frame (ORF)1a and ORF1b regions, while they clustered with lineage 2 in
      the ORF2 region. Remarkably, one of 15 strains exhibited low amino acid sequence
      similarity to other BoAstVs and was clustered separately with porcine astrovirus
      type 5 in all trees, and ovine astrovirus in the ORF2 region, suggesting past
      interspecies transmission. 

PMID- 26212365
TI  - Fanconi Anemia Mesenchymal Stromal Cells-Derived Glycerophospholipids Skew
      Hematopoietic Stem Cell Differentiation Through Toll-Like Receptor Signaling.
AB  - Fanconi anemia (FA) patients develop bone marrow (BM) failure or leukemia. One
      standard care for these devastating complications is hematopoietic stem cell
      transplantation. We identified a group of mesenchymal stromal cells (MSCs)
      derived metabolites, glycerophospholipids, and their endogenous inhibitor, 5
      (tetradecyloxy)-2-furoic acid (TOFA), as regulators of donor hematopoietic stem
      and progenitor cells. We provided two pieces of evidence that TOFA could improve
      hematopoiesis-supporting function of FA MSCs: (a) limiting-dilution cobblestone
      area-forming cell assay revealed that TOFA significantly increased cobblestone
      colonies in Fanca-/- or Fancd2-/- cocultures compared to untreated cocultures.
      (b) Competitive repopulating assay using output cells collected from cocultures
      showed that TOFA greatly alleviated the abnormal expansion of the donor myeloid
      (CD45.2+Gr1+Mac1+) compartment in both peripheral blood and BM of recipient mice
      transplanted with cells from Fanca-/- or Fancd2-/- cocultures. Furthermore,
      mechanistic studies identified Tlr4 signaling as the responsible pathway
      mediating the effect of glycerophospholipids. Thus, targeting glycerophospholipid
      biosynthesis in FA MSCs could be a therapeutic strategy to improve hematopoiesis
      and stem cell transplantation.

PMID- 26212366
TI  - Discovery of Novel Peptidomimetics as Irreversible CHIKV NsP2 Protease Inhibitors
      Using Quantum Mechanical-Based Ligand Descriptors.
AB  - Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. Recent outbreaks of
      CHIKV infections have been reported in Asia, Africa, and Europe. The symptoms of
      CHIKV infection include fever, headache, nausea, vomiting, myalgia, rash, and
      chronic persistent arthralgia. To date, no vaccines or selective antiviral drugs
      against this important emerging virus have been reported. In this study, the
      design, synthesis, and antiviral activity screening of new topographical
      peptidomimetics revealed three potential prototype agents 3a, 4b, and 5d showing
      93-100% maximum inhibition of CHIKV replication in cell-based assay having EC90
      of 8.76-9.57 MUg/mL. Intensive molecular modeling studies including covalent
      docking, lowest unoccupied molecular orbital energies, and the atomic condensed
      Fukui functions calculations strongly suggested the covalent binding of
      peptidomimetics 3a, 4b, and 5d to CHIKV nsP2 protease leading to permanent enzyme
      inactivation via Michael adduct formation between alpha/beta-unsaturated ketone
      functionality in our designed peptidomimetics and active site catalytic
      cysteine1013. Furthermore, small molecular weight peptidomimetics 3a and 4b
      satisfied the Lipinski rule of five for drug-likeness and showed promising
      intestinal absorption and aqueous solubility via computational admet studies
      making them promising hits for further optimization. 

PMID- 26212367
TI  - A novel SNP in 3' UTR of INS gene: A case report of neonatal diabetes mellitus.
AB  - Neonatal diabetes mellitus (NDM) is a rare condition with a prevalence of 1 in
      300,000 live births. We have found 3 known SNPs in 5'UTR and a novel SNP in 3'
      UTR in the INS gene. These SNPs were present in 9-month-old girl from Saudi
      Arabia and also present in the father and mother. The novel SNP we found is not
      present in 1000 Genome project or other databases. Further, the newly identified
      3' UTR mutation in the INS gene may abolish the polyadenylation signal and result
      in severe RNA instability. 

PMID- 26212368
TI  - Immediate control of acute intracystic arterial hemorrhage after EUS-FNA by EUS
      guided fine-needle injection.

PMID- 26212369
TI  - Comprehensive analysis of efficacy and safety of peroral endoscopic myotomy
      performed by a gastroenterologist in the endoscopy unit: a single-center
      experience.
AB  - BACKGROUND AND AIMS: The safety and efficacy of peroral endoscopic myotomy (POEM)
      when performed by gastroenterologists in the endoscopy unit are currently
      unknown. The aims of this study were to assess (1) the safety and efficacy of
      POEM in which all procedures were performed by 1 gastroenterologist in the
      endoscopy unit, and (2) the predictors of adverse events and nonresponse.
      METHODS: All consecutive patients who underwent POEM at 1 tertiary center were
      included. Clinical response was defined by a decrease in the Eckardt score to 3
      or lower. Adverse events were graded according to the American Society for
      Gastrointestinal Endoscopy lexicon's severity grading system. RESULTS: A total of
      60 consecutive patients underwent POEM in the endoscopy suite with a mean
      procedure length of 99 minutes. The mean length of submucosal tunnel was 14 cm
      and the mean myotomy length was 11 cm. The median length of hospital stay was 1
      day. Among 52 patients with a mean follow-up period of 118 days (range 30-750),
      clinical response was observed in 48 patients (92.3%). There was a significant
      decrease in Eckardt score after POEM (8 vs 1.19, P < .0001). The mean lower
      esophageal sphincter pressure decreased significantly after POEM (29 mm Hg vs 11
      mm Hg, P < .0001). A total of 10 adverse events occurred in 10 patients (16.7%):
      7 rated as mild, 3 as moderate, and none as severe. Procedure length was the only
      predictor of adverse events (P = .01). pH impedance testing was completed in 25
      patients, and 22 (88%) had abnormal acid exposure, but positive symptom
      correlation was present in only 6 patients. All patients with symptomatic reflux
      were successfully treated with proton pump inhibitors. CONCLUSIONS: POEM can be
      effectively and safely performed by experienced gastroenterologists at a tertiary
      care endoscopy unit. Adverse events are infrequent, and most can be managed
      intraprocedurally. Post-POEM reflux is frequent but can be successfully managed
      medically.

PMID- 26212370
TI  - Cortical thickness in de novo patients with Parkinson disease and mild cognitive
      impairment with consideration of clinical phenotype and motor laterality.
AB  - BACKGROUND AND PURPOSE: Parkinson's disease (PD) is a progressive
      neurodegenerative disorder with motor and non-motor symptoms, including cognitive
      deficits. Several magnetic resonance imaging approaches have been applied to
      investigate brain atrophy in PD. The aim of this study was to detect early
      structural cortical and subcortical changes in de novo PD whilst distinguishing
      cognitive status, clinical phenotype and motor laterality. METHODS: Eighteen de
      novo PD with mild cognitive impairment (PD-MCI), 18 de novo PD without MCI (PD
      NC) and 18 healthy control subjects were evaluated. In the PD-MCI group, nine
      were tremor dominant and nine were postural instability gait disorder (PIGD)
      phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom
      dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical
      structures and to study group differences as well as the association with
      clinical and neuropsychological data. RESULTS: Parkinson's disease with MCI
      showed regional thinning in the right frontal, right middle temporal areas and
      left insula compared to PD-NC. A reduction of the volume of the left and right
      thalamus and left hippocampus was found in PD-MCI compared to PD-NC. PD-MCI PIGD
      showed regional thinning in the right inferior parietal area compared to healthy
      controls. A decreased volume of the left thalamus was reported in PD-MCI with
      right-sided symptom dominance compared to PD-NC and PD-MCI with left-sided
      symptom dominance. CONCLUSIONS: When MCI was present, PD patients showed a fronto
      temporo-parietal pattern of cortical thinning. This cortical pattern does not
      appear to be influenced by motor laterality, although one-sided symptom dominance
      may contribute to volumetric reduction of specific subcortical structures.

PMID- 26212371
TI  - Measuring parental and family efficacy beliefs of adolescents' parents: Cross
      cultural comparisons in Italy and Portugal.
AB  - The goal of this study was to examine the psychometric properties of the
      Perceived Parental Self-Efficacy (PPSE) and Perceived Family Collective Efficacy
      (PFCE) revised scales in the Portuguese and Italian contexts. To this aim two
      studies were conducted: the first reported the exploratory and confirmatory
      factor analyses with Portuguese samples, whereas the second addressed the cross
      cultural invariance of PPSE and PFCE (Portugal and Italy). Results of the first
      study showed the appropriate fit of the unifactorial model of both scales to
      Portuguese data. The invariance analyses performed in the second study attested
      to the PPSE and PFCE's configural, metric and scalar invariance in both
      countries. The correlations of PPSE and PFCE with communication, management of
      conflict and children's school achievement further attested to their construct
      and practical validity. Thus, PPSE and PFCE proved to be suitable to further use
      in research and psychological assessment fields.

PMID- 26212372
TI  - Effects of a 12-day maximal shuttle-run shock microcycle in hypoxia on soccer
      specific performance and oxidative stress.
AB  - The purpose of this study was to investigate the effect of a maximal shuttle-run
      shock microcycle in hypoxia on repeated sprint ability (RSA, 6 * 40-m (6 * 20 m
      back and forth, 20" rest in between)), Yo-Yo-intermittent-recovery (YYIR) test
      performance, and redox-status. Fourteen soccer players (age: 23.9 +/- 2.1 years),
      randomly assigned to hypoxia (~ 3300 m) or normoxia training, performed 8 maximal
      shuttle-run training sessions within 12 days. YYIR test performance and RSA
      fatigue-slope improved independently of the hypoxia stimulus (p < 0.05). Training
      reduced the oxidative stress level (-7.9%, p < 0.05), and the reduction was
      associated with performance improvements (r = 0.761, DeltaRSA; r = -0.575,
      DeltaYYIR, p < 0.05).

PMID- 26212373
TI  - An overview of experimental and investigational multikinase inhibitors for the
      treatment of metastatic colorectal cancer.
AB  - INTRODUCTION: The era of molecular-targeted agents, particularly bevacizumab and
      cetuximab, has revolutionized the treatment paradigm for metastatic colorectal
      cancer (mCRC). Amongst the multikinase inhibitors (MKIs) examined, regorafenib
      was the first to establish its role in mCRC. Despite its modest efficacy, this
      finding had reignited interest in exploring MKIs with the hope of maximizing
      their therapeutic potential in mCRC. AREAS COVERED: This review summarizes the
      previous studies of MKIs in mCRC, targeting two signaling pathways activated
      through vascular endothelial growth factor receptors and epidermal growth factor
      receptors. The article provides discussion with a focus on: the challenges
      encountered when combining MKI with chemotherapy, the lack of predictive markers,
      and strategies utilized to address escape pathways through combining MKIs with
      other targeted agents. EXPERT OPINION: Clinical progress using MKIs in mCRC has
      been disappointing due to their limited efficacy. The exact role of regorafenib,
      apart from in chemo-refractory disease setting, requires further delineation. The
      role of MKIs in combination with other targeted agents or chemotherapy and in the
      maintenance setting is still considered experimental and warrants further
      investigation. The broader role of the current generation of MKIs will depend
      upon the accurate identification of patients with specific molecular phenotypes
      and better pharmacodynamic understanding of these agents to minimize toxicity.

PMID- 26212374
TI  - Is Heart Rate Variability Related to Season of Birth?
AB  - BACKGROUND: Season of birth (SOB) has been found to be related to cardiovascular
      mortality, but the mechanisms are unclear. It is suggested that birth in winter
      is a protective factor for the circulatory system, and this should be able to be
      observed using heart rate variability (HRV) measurements. The phenomenon may have
      a sex difference and is likely to be modulated by climatic factors. This study
      focused on this problem and investigates healthy school-age children to minimize
      confounding factors. HYPOTHESIS: Birth in winter is protective to cardiovascular
      system via autonomic modulation. There is a gender difference in the relationship
      between SOB and autonomic activity. Climatic factors are the cause of SOB effects
      on autonomic system. METHODS: A total of 381 healthy school-age children were
      recruited for this study. Their HRV profiles were measured once and climatic
      information related to their month of birth was gathered. The HRV profiles of the
      2 sexes and 4 seasons of birth were compared. Correlation and regression analysis
      were performed to clarify the relationship between climatic factors and the HRV
      results. RESULTS: Boys born in winter have higher high-frequency power (HF) but a
      lower ratio of low-frequency power to high-frequency power (LF/HF) than do males
      born in other seasons. This result is not found for girls. Age and the
      temperature of the SOB are predictive factors for HF among boys. The humidity of
      SOB is a predictive factor for normalized low-frequency power (LF%) and LF/HF
      among girls. CONCLUSIONS: Season of birth is related to both parasympathetic and
      sympathetic activity among school-age children, especially boys. Temperature and
      humidity are potential causes of this SOB phenomenon.

PMID- 26212375
TI  - Lysosomal pH Plays a Key Role in Regulation of mTOR Activity in Osteoclasts.
AB  - Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in the
      regulation of cell growth. It has been shown to play an important role in
      osteoclast differentiation, particularly at the earlier stages of
      osteoclastogenesis. mTOR activation and function, as part of mTORC1 complex, is
      dependent on lysosomal localization and the vacuolar H(+) -ATPase (V-ATPase)
      activity; however, the precise mechanism is still not well understood. Using
      primary mouse osteoclasts that are known to have higher lysosomal pH due to R740S
      mutation in the V-ATPase a3 subunit, we investigated the role of lysosomal pH in
      mTORC1 signaling. Our results demonstrated that +/R740S cells had increased basal
      mTOR protein levels and mTORC1 activity compared to +/+ osteoclasts, while mTOR
      gene expression was decreased. Treatment with lysosomal inhibitors chloroquine
      and ammonium chloride, compounds known to raise lysosomal pH, significantly
      increased mTOR protein levels in +/+ cells, confirming the importance of
      lysosomal pH in mTOR signaling. These results also suggested that mTOR could be
      degraded in the lysosome. To test this hypothesis, we cultured osteoclasts with
      chloroquine or proteasomal inhibitor MG132. Both chloroquine and MG132 increased
      mTOR and p-mTOR protein levels in +/+ osteoclasts, suggesting that mTOR undergoes
      both lysosomal and proteasomal degradation. Treatment with cycloheximide, an
      inhibitor of new protein synthesis, confirmed that mTOR is constitutively
      expressed and degraded. These results show that, in osteoclasts, the lysosome
      plays a key role not only in mTOR activation but also in its deactivation through
      protein degradation, representing a novel molecular mechanism of mTOR regulation.

PMID- 26212376
TI  - [Fe19 ] "Super-Lindqvist" Aggregate and Large 3D Interpenetrating Coordination
      Polymer from Solvothermal Reactions of [Fe2 (OtBu)6 ] with Ethanol.
AB  - The syntheses, crystal structures, and physical properties of [HFe19 O14 (OEt)30
      ] and {Fe11 (OEt)24 }infinity are reported. [HFe19 O14 (OEt)30 ] has an
      octahedral shape. Its core with a central Fe metal ion surrounded by six MU6 -oxo
      ligands is arranged in the rock salt structure. {Fe11 (OEt)24 }infinity is a
      mixed-valence coordination polymer in which Fe(III) metal ions form three 3D
      interpenetrating (10,3)-b nets. The arrangement of the Fe(III) ions can also be
      compared to that of Si ions in alpha-ThSi2 . Thus, the described structures are
      at the interface between molecular and solid-state chemistry. 

PMID- 26212377
TI  - Synthesis of BiVO4@C Core-Shell Structure on Reduced Graphene Oxide with Enhanced
      Visible-Light Photocatalytic Activity.
AB  - Herein, a facile strategy for the controllable synthesis of BiVO4@C core-shell
      nanoparticles on reduced graphene oxide (RGO) is reported. The BiVO4 particle
      size can be controlled in the process by adjusting the volume ratio of glycerol
      in the sol-gel solution. The glycerol layers adsorbed on BiVO4 (BiVO4@glycerol)
      made it possible to form hydrogen bonds between BiVO4@glycerol and graphene oxide
      with the assistance of ultrasound. After thermal treatment, glycerol adsorbed on
      the BiVO4 particles formed amorphous carbon shells to link the particles and RGO.
      As a result, the obtained RGO-BiVO4@C nanocomposite showed a five times higher
      rate in O2 evolution from water under visible-light irradiation. Also, it
      demonstrated a six times higher photocatalytic performance enhancement than that
      of pure BiVO4 in the degradation of Rhodamine B. The enhanced performance is
      attributed to the carbon shells that restrict the growth of BiVO4 , the reduced
      graphene oxide that improves the electronic conductivity of the composite, and
      importantly, the bonds formed between the carbon shells and RGO that reduce the
      recombination loss of photogenerated charges effectively. The strategy is simple,
      effective, and can be extended to other ternary oxides with controlled size and
      high performance.

PMID- 26212378
TI  - Clinical profiles and treatment outcomes of systemic corticosteroids for toxic
      epidermal necrolysis: A retrospective study.
AB  - Toxic epidermal necrolysis (TEN) is an uncommon severe cutaneous adverse
      reaction. Although controversies remain in the pathophysiology and management of
      this condition, improvements in survival and morbidity have been observed over
      the past decade. The aim of the present study was to demonstrate the clinical
      profiles of TEN in Thai patients and the treatment outcome with dexamethasone
      pulse therapy assessed by using the Severity of Illness Score for Toxic Epidermal
      Necrolysis (SCORTEN). Medical records of all patients with TEN were collected
      retrospectively from January 2002 to December 2012. Epidemiological features,
      etiologies, treatments and clinical outcomes were reviewed. Of 18 patients, the
      female to male ratio was 1:1 and the mean age was 49.7 years. Cephalosporins
      (27.8%), phenytoin (16.7%), carbamazepine, sulfonamide drugs and allopurinol
      (11.1% each) were implicated as leading causes of TEN. Hepatitis was the most
      frequent complication (77.8%). Pulsed high doses of dexamethasone 1-1.5 mg/kg per
      day for a short period were administrated in all cases. Two of the 18 patients
      receiving corticosteroids (SCORTEN 5 and 6) died. The mortality rate was 11%
      (2/18 patients), however, no patient receiving systemic corticosteroids died if
      the patients had less than 4 points on SCORTEN. The clinical features of Thai
      patients with TEN were similar to other reports. In conclusion, in addition to
      withdrawal of the suspected agent and intensive supportive care, the
      administration of short-term dexamethasone pulse therapy, particularly during the
      initial phase, may be beneficial in reducing the mortality rate. 

PMID- 26212379
TI  - Endoscopic and operative treatment of delayed complications after pancreatic
      trauma: An analysis of 27 civilians treated in an academic Level 1 Trauma Centre.
AB  - BACKGROUND: This study evaluated the efficacy of endoscopic treatment of delayed
      local complications including pseudocysts and persistent pancreatic fistulae in a
      cohort of civilian patients who had previously sustained a pancreatic injury.
      METHOD: A large institutional database was interrogated to identify patients who
      developed a delayed pancreatic complication among those with pancreatic injuries
      treated between January 1990 and December 2013. The degree of the pancreatic duct
      injury was graded using a new duct injury grading system and endoscopic
      therapeutic outcome assessed according to the grade of injury. RESULTS: During
      the period under review, 432 consecutive patients were treated for pancreatic
      injuries of whom 27 (20 men, 7 women, median age 31, range 15-68 years) presented
      with delayed complications related to the initial pancreatic injury. Sixteen
      patients had non-resolving symptomatic pancreatic pseudocysts, 10 had persistent
      pancreatic fistulae and 1 had a symptomatic duct stricture. Fourteen patients
      with grade 2a, 3a, 3b or 4c main pancreatic duct injuries were successfully
      treated endoscopically with either pancreatic duct stenting or pseudocyst
      drainage while 13 patients with grade 4a or 4b duct injuries who had complete
      duct division with a disconnected duct syndrome failed endoscopic management and
      required surgical intervention. The 27 patients underwent a total of 49
      endoscopic procedures (47 elective, 2 emergency) of whom 4 developed
      complications related to the endoscopic treatment. All 4 resolved, 2 after urgent
      endoscopic re-intervention. CONCLUSION: In this preliminary analysis the Cape
      Town pancreatic ductal injury grading classification showed a close correlation
      with outcome after endoscopic and operative intervention.

PMID- 26212381
TI  - Trans Fatty Acid and Coronary Artery Disease- Lessons From Seven Countries Study.

PMID- 26212380
TI  - Neurological and endocrine phenotypes of fragile X carrier women.
AB  - Women who carry fragile X mental retardation 1 (FMR1)gene premutation expansions
      frequently report neurological or endocrine symptoms and prior studies have
      predominantly focused on questionnaire report of medical issues. Premutation
      carrier (PMC) women (n = 33) and non-carrier controls (n = 13) were recruited and
      evaluated by a neurologist, neuropsychologist, and endocrinologist. Blood and
      skin biopsies were collected for molecular measures. Scales for movement
      disorders, neuropathy, cognitive function, psychiatric symptoms, sleep, and
      quality of life were completed. The average age of the women was 51 years (n =
      46) and average CGG repeat size was 91 +/- 24.9 in the FMR1 PMC women. Seventy
      percent of the PMC women had an abnormal neurological examination. PMC women had
      significantly higher scores on the Fragile X-Associated Tremor Ataxia Syndrome
      (FXTAS) rating scale, more neuropathy, and difficulty with tandem gait compared
      to controls. Central sensitivity syndromes, a neuroticism profile on the NEO
      Personality Profile, and sleep disorders were also prevalent. Discrepancies
      between subject report and examination findings were also seen. This pilot study
      suggests that women with the FMR1 premutation may have a phenotype that overlaps
      with that seen in FXTAS. Additional research with larger sample sizes is
      warranted to better delineate the clinical features.

PMID- 26212382
TI  - Corrigendum: Rethinking Indian monsoon rainfall prediction in the context of
      recent global warming.

PMID- 26212384
TI  - Facile synthesis of porous Bi2WO6 nanosheets with high photocatalytic
      performance.
AB  - Compared with the well-known three-dimensional Bi2WO6 nanosheet-assembled
      nanostructures, the free-standing two-dimensional porous Bi2WO6 nanosheets have
      seldom been reported. The possible reason is that Bi2WO6 nanosheets with a high
      surface-to-volume ratio usually tend to self-assemble or aggregate to form
      microspheres to reduce their surface energy. To prevent their aggregation, in
      this study, a new and facile self-assembled route, which includes the in situ ion
      exchange reaction of Na2WO4 solution with the Bi(NO3)3 solid powder and the
      following high-temperature calcination, has been successfully developed to
      prepare the free-standing porous Bi2WO6 nanosheets. The ion-exchange reaction
      between the Bi(NO3)3 solid and Na2WO4 solution can in situ produce amorphous
      Bi2WO6 nanosheets, while the high-temperature calcination (500  degrees C) causes
      the formation of homogeneously porous structures in individual nanosheets during
      their phase transformation from amorphous to crystalline. The resultant porous
      nanosheets are composed of one-layer Bi2WO6 nanoparticles with a size of 30-50
      nm, and there is a strong coupling interface among these nanoparticles.
      Photocatalytic experimental results suggest that the resultant porous Pt/Bi2WO6
      nanosheets show a high photocatalytic performance for the decomposition of phenol
      solution. Considering their facile preparation, the present synthetic route may
      provide new insights for the design and fabrication of other nanostructured
      materials with various potential applications. 

PMID- 26212383
TI  - GABA(B) receptors couple to Galphaq to mediate increases in voltage-dependent
      calcium current during development.
AB  - Metabotropic GABA(B) receptors are known to modulate the activity of voltage
      dependent calcium channels. Previously, we have shown that GABA(B) receptors
      couple to a non-Gi/o G-protein to enhance calcium influx through L-type calcium
      channels by activating protein kinase C in neonatal rat hippocampal neurons. In
      this study, the components of this signaling pathway were investigated further.
      Galphaq was knocked down using morpholino oligonucleotides prior to examining
      GABA(B) -mediated enhancement of calcium influx. When Galphaq G-proteins were
      eliminated using morpholino-mediated knockdown, the enhancing effects of the
      GABA(B) receptor agonist baclofen (10 MUM) on calcium current or entry were
      eliminated. These data suggest that GABA(B) receptors couple to Galphaq to
      regulate calcium influx. Confocal imaging analysis illustrating colocalization of
      GABA(B) receptors with Galphaq supports this hypothesis. Furthermore, baclofen
      treatment caused translocation of PKCalpha (protein kinase C alpha) but not
      PKCbeta or PKCepsilon, suggesting that it is the alpha isoform of PKC that
      mediates calcium current enhancement. Inhibition of calcium/calmodulin-dependent
      kinase II did not affect the baclofen-mediated enhancement of calcium levels. In
      summary, activation of GABA(B) receptors during development leads to increased
      calcium in a subset of neurons through Galphaq signaling and PKCalpha activation
      without the involvement of calcium/calmodulin-dependent kinase II. Activation of
      GABA(B) receptors in the neonatal rat hippocampus enhances voltage-dependent
      calcium currents independently of Gi/o . In this study, knockdown of Galphaq with
      morpholino oligonucleotides abolished enhancement of calcium influx and protein
      kinase Calpha was activated by GABA(B) receptors. Therefore, we hypothesize that
      GABA(B) receptors couple to Gq to activate PKCalpha leading to enhancement of L
      type calcium current.

PMID- 26212385
TI  - Hydrodynamic instability in a magnetically driven suspension of paramagnetic red
      blood cells.
AB  - We investigate the magnetically driven motion in suspensions of paramagnetic
      particles. Our object is diluted deoxygenated whole blood with paramagnetic red
      blood cells (RBCs). We use direct observations in a closed vertical Hele-Shaw
      channel, and a well-defined magnetic force field applied horizontally in the
      channel plane. At very low cell concentrations, we register single-particle
      motion mode, track individual cells and determine their hydrodynamic and magnetic
      characteristics. Above 0.2 volume percent concentration, we observe local swirls
      and a global transient quasi-periodic vortex structure, intensifying with
      increasing cell concentration, but surprisingly this does not influence the time
      and purity of the magnetic extraction of RBCs. Our observations shed light on the
      behavioral complexity of magnetically driven submagnetic suspensions, an
      important issue for the emerging microfluidic technology of direct magnetic cell
      separation and intriguing for the mechanics of particulate soft matter. 

PMID- 26212386
TI  - A Retrospective Evaluation of Pediatric Major Trauma Related to Sport and
      Recreational Activities in Nova Scotia.
AB  - OBJECTIVES: A small proportion of pediatric sport- and recreation-related
      injuries are serious enough to be considered "major trauma." However, the
      immediate and long-term consequences in cases of pediatric major trauma are
      significant and potentially life-threatening. The objective of this study was to
      describe the incidence and outcomes of pediatric major traumas related to sport
      and recreational activities in Nova Scotia. METHODS: This study was a
      retrospective case series. Data on major pediatric traumas related to sport and
      recreational activities on a provincial scope were extracted from the Nova Scotia
      Trauma Program Registry between 2000 and 2013. We evaluated frequency, type,
      severity, and outcomes of major traumas. Outcomes assessed included length of
      hospital stay, admission to a special care unit (SCU), and mortality. RESULTS:
      Overall, 107 children aged three to 18 years sustained a major trauma (mean age
      12.5 [SD 3.8]; 84% male). Most injuries were blunt traumas (97%). The greatest
      proportion were from cycling (59, 53%), followed by hockey (8, 7%), skateboarding
      (7, 7%) and skiing (7, 7%). The Nova Scotia Pediatric Trauma Team was activated
      in 27% of cases. Mean in-hospital length of stay was five days (SD 5.6), and
      nearly half (49%) of patients required SCU admission. Severe traumatic brain
      injury occurred in 52% of cases, and mortality in five cases. CONCLUSIONS: Over a
      13-year period, the highest incidence of pediatric major trauma related to sport
      and recreational activities was from cycling, followed by hockey. Severe
      traumatic brain injury occurred in over half of pediatric major trauma patients.

PMID- 26212387
TI  - Human autoimmune diseases: a comprehensive update.
AB  - There have been significant advances in our understanding of human autoimmunity
      that have led to improvements in classification and diagnosis and, most
      importantly, research advances in new therapies. The importance of autoimmunity
      and the mechanisms that lead to clinical disease were first recognized about 50
      years ago following the pioneering studies of Macfarlane Burnett and his Nobel
      Prize-winning hypothesis of the 'forbidden clone'. Such pioneering efforts led to
      a better understanding not only of autoimmunity, but also of lymphoid cell
      development, thymic education, apoptosis and deletion of autoreactive cells.
      Contemporary theories suggest that the development of an autoimmune disease
      requires a genetic predisposition and environmental factors that trigger the
      immune pathways that lead, ultimately, to tissue destruction. Despite extensive
      research, there are no genetic tools that can be used clinically to predict the
      risk of autoimmune disease. Indeed, the concordance of autoimmune disease in
      identical twins is 12-67%, highlighting not only a role for environmental
      factors, but also the potential importance of stochastic or epigenetic phenomena.
      On the other hand, the identification of cytokines and chemokines, and their
      cognate receptors, has led to novel therapies that block pathological
      inflammatory responses within the target organ and have greatly improved the
      therapeutic effect in patients with autoimmune disease, particularly rheumatoid
      arthritis. Further advances involving the use of multiplex platforms for
      diagnosis and identification of new therapeutic agents should lead to major
      breakthroughs within the next decade. 

PMID- 26212388
TI  - The Effect of Thrombolytic, Anticoagulant, and Vasodilator Agents on the Survival
      of Random Pattern Skin Flap.
AB  - BACKGROUND: The aim of this study was to investigate the effect of subcutaneously
      applied thrombolytic, anticoagulant, and vasodilator agents on the survival of
      random-pattern skin flap. METHODS: A caudally based dorsal flap model was used in
      24 rats in four groups. In group 1 (n = 6), flap was elevated and sutured. In
      group 2 (n = 6), enoxaparin sodium was injected subcutaneously immediately after
      surgery, on days 1 and 2. In group 3 (n = 6), a transdermal nitroglycerin was
      applied directly following surgery, on days 1 and 2. In group 4 (n = 6),
      alteplase was injected subcutaneously immediately after surgery, on days 1 and 2.
      Blood flow was measured with laser Doppler flowmetry at the proximal and distal
      halves of flap before, immediately after surgery, and on days 3 and 7. Histologic
      samples were taken from the same locations on day 3 and day 7 postoperatively.
      Vessel and lymphocyte count was obtained. Photographs were taken to determine
      flap necrosis areas at day 7 postoperatively. RESULTS: Area of skin necrosis was
      found to be less in all medication groups. But only enoxaparin sodium group
      showed significant decrease in skin necrosis (p < 0.05). Laser Doppler flowmetry
      showed a gradual decrease in all groups over time, with no statistically
      significant result. The histologic findings revealed the induction of
      angiogenesis in all experimental groups. CONCLUSION: Subcutaneously applied
      thrombolytic, anticoagulant, and vasodilator agents increase random-pattern skin
      flap survival with only enoxaparin sodium showing significant decrease in flap
      necrosis.

PMID- 26212389
TI  - Attributable cost of obesity in breast surgery: a matched cohort analysis.
AB  - BACKGROUND: The purpose of this study was to determine the economic impact of
      obesity on patients undergoing mastectomy and breast conservation (BC) for breast
      cancer. METHODS: An analysis of female patients greater than or equal to 18 years
      undergoing mastectomy and BC for breast cancer between 2004 and 2010 using the
      Nationwide Inpatient Sample was conducted. RESULTS: Of 55,903 patients in our
      study (49,985 mastectomy, 5,918 BC), 3,308 patients (5.92%) were obese. After
      propensity score matching, the cost for obese patients was higher at $1,826 (P <
      .0001) for mastectomy and $1,702 for BC (P < .0001). These costs were not
      significantly associated with overall complications and length of stay for
      mastectomy in the matched comparison group and not associated with overall
      complications and minimally associated with longer length of stay in the BC
      group. CONCLUSION: By controlling for other patient factors, this study shows
      that obesity is attributable to a significantly higher cost for both BC (29%) and
      mastectomy (23%).

PMID- 26212390
TI  - Lymph node dissection in resectable perihilar cholangiocarcinoma: a systematic
      review.
AB  - BACKGROUND: Perihilar cholangiocarcinoma is usually unresectable at the time of
      diagnosis. Only few patients are candidates for a potential curative treatment.
      For those patients, prognosis is strongly related to negative resection margin
      and lymph node status. Thus, a certain benchmark of lymph node count is necessary
      to secure relevant lymph node recovery and to avoid understaging. However, the
      required minimum number of retrieved lymph nodes remains unclear for perihilar
      cholangiocarcinoma. The 7th American Joint Committee on Cancer tumor, nodes,
      metastases edition increased the requirement for the histologic examination of
      lymph nodes in perihilar cholangiocarcinoma patients from 3 to 15. The
      applicability of such recommendation appears difficult and questionable.
      Therefore, the purpose of this systematic review is to evaluate the number of
      retrieved lymph nodes for staging of patients undergoing surgery for perihilar
      cholangiocarcinoma. METHODS: The MEDLINE, EMBASE, and The Cochrane Library
      databases were systematically screened up to December 2014. All studies reporting
      the number of lymph node count in perihilar cholangiocarcinoma were included and
      assessed for eligibility. RESULTS: A total of 725 abstracts were screened and 20
      studies were included for analysis, comprising almost 4,000 patients. The
      cumulative median lymph node count was 7 (2 to 24). A median lymph node count
      greater than or equal to 15 was reported in 9% of perihilar cholangiocarcinoma
      patients and could only be achieved in extended lymphadenectomy. Subgroup
      analysis revealed a median lymph node count of 7 (range 7 to 9), which was
      associated with the detection of most lymph node positive patients and showed the
      lowest risk for understaging patients. Lymph node count greater than or equal to
      15 did not increase detection rate of lymph node positive patients. CONCLUSIONS:
      This systematic analysis suggests that lymph node count greater than or equal to
      7 is adequate for prognostic staging, while lymph node count greater than or
      equal to 15 does not improve detection of patients with positive lymph nodes.

PMID- 26212392
TI  - Low defect large area semi-polar (11[Formula: see text]2) GaN grown on patterned
      (113) silicon.
AB  - We report on the growth of semi-polar GaN (11[Formula: see text]2) templates on
      patterned Si (113) substrates. Trenches were etched in Si (113) using KOH to
      expose Si {111} sidewalls. Subsequently an AlN layer to prevent meltback etching,
      an AlGaN layer for stress management, and finally two GaN layers were deposited.
      Total thicknesses up to 5 [Formula: see text]m were realised without cracks in
      the layer. Transmission electron microscopy showed that most dislocations
      propagate along [0001] direction and hence can be covered by overgrowth from the
      next trench. The defect densities were below [Formula: see text] and stacking
      fault densities less than 100 cm [Formula: see text]. These numbers are similar
      to reports on patterned r-plane sapphire. Typical X-ray full width at half
      maximum (FHWM) were 500" for the asymmetric (00.6) and 450" for the (11.2)
      reflection. These FHWMs were 50 % broader than reported for patterned r-plane
      sapphire which is attributed to different defect structures and total
      thicknesses. The surface roughness shows strong variation on templates. For the
      final surface roughness the roughness of the sidewalls of the GaN ridges at the
      time of coalescence are critical.

PMID- 26212391
TI  - Heart rate variability analysis is more sensitive at identifying neonatal sepsis
      than conventional vital signs.
AB  - BACKGROUND: Sepsis remains the largest preventable source of neonatal mortality
      in the world. Heart rate variability (HRV) analysis and noninvasive cardiac
      output have been shown to be useful adjuncts to sepsis detection in many patient
      groups. METHODS: With Institutional Review Board approval, 4 septic and 6
      nonseptic extremely low birth weight patients were enrolled. Data from septic and
      healthy patients were collected for 5 hours. Electrocardiogram waveform and
      traditional vital signs were collected and the RR intervals were calculated; then
      HRV analysis was performed in both the time and frequency domain. RESULTS: HRV
      measurements in time domain, heart rate, and pulse oximetry (SpO2) were
      significantly different in septic patients vs nonseptic controls. CONCLUSIONS:
      These results indicate that nonconventional vital signs such as HRV are more
      sensitive than traditionally used vital signs, such as cardiac output and mean
      arterial pressure, in the confirmation of sepsis in extremely low birth weight
      neonates. HRV may allow for earlier identification of septic physiology.

PMID- 26212393
TI  - Subsidy and parental attitudes toward pediatric health care in the Tokyo
      metropolitan area.
AB  - BACKGROUND: In Japan, the number of municipalities that offer free medical care
      for children has increased. This policy, however, might unintentionally aggravate
      the overcrowded situation of pediatric ambulatory services in Japan. We
      investigated the relationship between parents' health-care seeking attitudes
      according to child symptom severity and the amount of copayment, as well as
      parents' socioeconomic and demographic factors. METHODS: We used data for 4385
      people from the Japanese Study of Stratification, Health, Income and Neighborhood
      (J-SHINE), which consisted of stratified random sampling of those aged from 25 to
      50 years who lived in Tokyo and neighboring areas. Outcome variables were
      respondent health-care seeking attitudes toward their children's mild and severe
      symptoms of cold. Logistic regression models were developed for each dependent
      variable. RESULTS: A total of 1606 respondents with one or more children under
      the age of 15 years were included in the analysis. For mild symptoms of cold, no
      subsidy (OR: 0.51, 95%CI: 0.38-0.69) and partial subsidy (OR, 0.71; 95%CI: 0.54
      0.95) were associated with fewer "visit on that day" answers, compared with full
      subsidy. Income and respondent educational level were not associated with the
      outcome. For severe symptoms of cold, the OR of no subsidy (0.61; 95%CI: 0.30
      1.23) and that of partial subsidy (0.91; 95%CI: 0.40-2.07) were not statistically
      significant. CONCLUSION: Imposing a small copayment might prevent visits to
      medical facilities for mild symptoms of cold, but will not prevent visits for
      severe symptoms of cold.

PMID- 26212394
TI  - Markers of health and disease and pigmented spots in a middle-aged population.

PMID- 26212395
TI  - Traumatic Brain Injury Rehabilitation Comparative Effectiveness Research:
      Introduction to the Traumatic Brain Injury-Practice Based Evidence Archives
      Supplement.
AB  - This supplement of the Archives of Physical Medicine and Rehabilitation is
      devoted to the Traumatic Brain Injury-Practice Based Evidence study, the first
      practice-based evidence study, to our knowledge, of traumatic brain injury
      rehabilitation. The purpose of this preface is to place this study in the broader
      context of comparative effectiveness research and introduce the articles in the
      supplement. 

PMID- 26212396
TI  - Traumatic Brain Injury-Practice Based Evidence Study: Design and Patients,
      Centers, Treatments, and Outcomes.
AB  - OBJECTIVES: To describe study design, patients, centers, treatments, and outcomes
      of a traumatic brain injury (TBI) practice-based evidence (PBE) study and to
      evaluate the generalizability of the findings to the U.S. TBI inpatient
      rehabilitation population. DESIGN: Prospective, longitudinal, observational
      study. SETTING: Ten inpatient rehabilitation centers. PARTICIPANTS: Patients
      (N=2130) enrolled between October 2008 and September 2011 and admitted for
      inpatient rehabilitation after an index TBI injury. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Return to acute care during rehabilitation,
      rehabilitation length of stay, FIM at discharge, residence at discharge, and 9
      months postdischarge rehospitalization, FIM, participation, and subjective well
      being. RESULTS: The level of admission FIM cognitive score was found to create
      relatively homogeneous subgroups for the subsequent analysis of best treatment
      combinations. There were significant differences in patient and injury
      characteristics, treatments, rehabilitation course, and outcomes by admission FIM
      cognitive subgroups. TBI-PBE study patients were overall similar to U.S. national
      TBI inpatient rehabilitation populations. CONCLUSIONS: This TBI-PBE study
      succeeded in capturing naturally occurring variation in patients and treatments,
      offering opportunities to study best treatments for specific patient impairments.
      Subsequent articles in this issue report differences between patients and
      treatments and associations with outcomes in greater detail.

PMID- 26212397
TI  - Institutional Variation in Traumatic Brain Injury Acute Rehabilitation Practice.
AB  - OBJECTIVE: To describe institutional variation in traumatic brain injury (TBI)
      inpatient rehabilitation program characteristics and evaluate to what extent
      patient factors and center effects explain how TBI inpatient rehabilitation
      services are delivered. DESIGN: Secondary analysis of a prospective, multicenter,
      cohort database. SETTING: TBI inpatient rehabilitation programs. PARTICIPANTS:
      Patients with complicated mild, moderate, or severe TBI (N=2130). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Mean minutes; number of treatment
      activities; use of groups in occupational therapy, physical therapy, speech
      therapy, therapeutic recreation, and psychology inpatient rehabilitation
      sessions; and weekly hours of treatment. RESULTS: A wide variation was observed
      between the 10 TBI programs, including census size, referral flow, payer mix,
      number of dedicated beds, clinician experience, and patient characteristics. At
      the centers with the longest weekday therapy sessions, the average session
      durations were 41.5 to 52.2 minutes. At centers with the shortest weekday
      sessions, the average session durations were approximately 30 minutes. The
      centers with the highest mean total weekday hours of occupational, physical, and
      speech therapies delivered twice as much therapy as the lowest center. Ordinary
      least-squares regression modeling found that center effects explained
      substantially more variance than patient factors for duration of therapy
      sessions, number of activities administered per session, use of group therapy,
      and amount of psychological services provided. CONCLUSIONS: This study provides
      preliminary evidence that there is significant institutional variation in
      rehabilitation practice and that center effects play a stronger role than patient
      factors in determining how TBI inpatient rehabilitation is delivered.

PMID- 26212398
TI  - Effects of Patient Preinjury and Injury Characteristics on Acute Rehabilitation
      Outcomes for Traumatic Brain Injury.
AB  - OBJECTIVE: To examine associations of patient and injury characteristics with
      outcomes at inpatient rehabilitation discharge and 9 months postdischarge for
      patients with traumatic brain injury (TBI). DESIGN: Prospective, longitudinal
      observational study. SETTING: Inpatient rehabilitation centers. PARTICIPANTS:
      Consecutive patients (N=2130) enrolled between 2008 and 2011, admitted for
      inpatient rehabilitation after index TBI, and divided into 5 subgroups based on
      rehabilitation admission FIM cognitive score. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Rehabilitation length of stay, discharge to home, and FIM at
      discharge and 9 months postdischarge. RESULTS: Severity indices increased
      explained variation in outcomes beyond that accounted for by patient
      characteristics. FIM motor scores were generally the most predictable. Higher
      functioning subgroups had more predictable outcomes then subgroups with lower
      cognitive function at admission. Age at injury, time from injury to
      rehabilitation admission, and functional independence at rehabilitation admission
      were the most consistent predictors across all outcomes and subgroups.
      CONCLUSIONS: Findings from previous studies of the relations among patient and
      injury characteristics and rehabilitation outcomes were largely replicated.
      Discharge outcomes were most strongly associated with injury severity
      characteristics, whereas predictors of functional independence at 9 months
      postdischarge included both patient and injury characteristics.

PMID- 26212399
TI  - Occupational, Physical, and Speech Therapy Treatment Activities During Inpatient
      Rehabilitation for Traumatic Brain Injury.
AB  - OBJECTIVE: To describe the use of occupational therapy (OT), physical therapy
      (PT), and speech therapy (ST) treatment activities throughout the acute
      rehabilitation stay of patients with traumatic brain injury. DESIGN: Multisite
      prospective observational cohort study. SETTING: Inpatient rehabilitation
      settings. PARTICIPANTS: Patients (N=2130) admitted for initial acute
      rehabilitation after traumatic brain injury. Patients were categorized on the
      basis of admission FIM cognitive scores, resulting in 5 fairly homogeneous
      cognitive groups. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Percentage of patients engaged in specific activities and mean time patients
      engaged in these activities for each 10-hour block of time for OT, PT, and ST
      combined. RESULTS: Therapy activities in OT, PT, and ST across all 5 cognitive
      groups had a primary focus on basic activities. Although advanced activities
      occurred in each discipline and within each cognitive group, these advanced
      activities occurred with fewer patients and usually only toward the end of the
      rehabilitation stay. CONCLUSIONS: The pattern of activities engaged in was both
      similar to and different from patterns seen in previous practice-based evidence
      studies with different rehabilitation diagnostic groups.

PMID- 26212400
TI  - Patient Effort in Traumatic Brain Injury Inpatient Rehabilitation: Course and
      Associations With Age, Brain Injury Severity, and Time Postinjury.
AB  - OBJECTIVE: To describe patients' level of effort in occupational, physical, and
      speech therapy sessions during traumatic brain injury (TBI) inpatient
      rehabilitation and to evaluate how age, injury severity, cognitive impairment,
      and time are associated with effort. DESIGN: Prospective, multicenter,
      longitudinal cohort study. SETTING: Acute TBI rehabilitation programs.
      PARTICIPANTS: Patients (N=1946) receiving 138,555 therapy sessions.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Effort in rehabilitation
      sessions rated on the Rehabilitation Intensity of Therapy Scale, FIM,
      Comprehensive Severity Index brain injury severity score, posttraumatic amnesia
      (PTA), and Agitated Behavior Scale (ABS). RESULTS: The Rehabilitation Intensity
      of Therapy Scale effort ratings in individual therapy sessions closely conformed
      to a normative distribution for all 3 disciplines. Mean Rehabilitation Intensity
      of Therapy Scale ratings for patients' therapy sessions were higher in the
      discharge week than in the admission week (P<.001). For patients who completed 2,
      3, or 4 weeks of rehabilitation, differences in effort ratings (P<.001) were
      observed between 5 subgroups stratified by admission FIM cognitive scores and
      over time. In linear mixed-effects modeling, age and Comprehensive Severity Index
      brain injury severity score at admission, days from injury to rehabilitation
      admission, days from admission, and daily ratings of PTA and ABS score were
      predictors of level of effort (P<.0001). CONCLUSIONS: Patients' level of effort
      can be observed and reliably rated in the TBI inpatient rehabilitation setting
      using the Rehabilitation Intensity of Therapy Scale. Patients who sustain TBI
      show varying levels of effort in rehabilitation therapy sessions, with effort
      tending to increase over the stay. PTA and agitated behavior are primary risk
      factors that substantially reduce patient effort in therapies.

PMID- 26212401
TI  - Enteral Nutrition for Patients With Traumatic Brain Injury in the Rehabilitation
      Setting: Associations With Patient Preinjury and Injury Characteristics and
      Outcomes.
AB  - OBJECTIVE: To determine the association of enteral nutrition (EN) with patient
      preinjury and injury characteristics and outcomes for patients receiving
      inpatient rehabilitation after traumatic brain injury (TBI). DESIGN: Prospective
      observational study. SETTING: Nine rehabilitation centers. PARTICIPANTS: Patients
      (N=1701) admitted for first full inpatient rehabilitation after TBI.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FIM at rehabilitation
      discharge, length of stay, weight loss, and various infections. RESULTS: There
      were many significant differences in preinjury and injury characteristics between
      patients who received EN and patients who did not. After matching patients with a
      propensity score of >40% for the likely use of EN, patients receiving EN with
      either a standard or a high-protein formula (>20% of calories coming from
      protein) for >25% of their rehabilitation stay had higher FIM motor and cognitive
      scores at rehabilitation discharge and less weight loss than did patients with
      similar characteristics not receiving EN. CONCLUSIONS: For patients receiving
      inpatient rehabilitation after TBI and matched on a propensity score of >40% for
      the likely use of EN, clinicians should strongly consider, when possible, EN for
      >=25% of the rehabilitation stay and especially with a formula that contains at
      least 20% protein rather than a standard formula.

PMID- 26212402
TI  - Psychotropic Medication Use During Inpatient Rehabilitation for Traumatic Brain
      Injury.
AB  - OBJECTIVE: To describe psychotropic medication administration patterns during
      inpatient rehabilitation for traumatic brain injury (TBI) and their relation to
      patient preinjury and injury characteristics. DESIGN: Prospective observational
      cohort. SETTING: Multiple acute inpatient rehabilitation units or hospitals.
      PARTICIPANTS: Individuals with TBI (N=2130; complicated mild, moderate, or
      severe) admitted for inpatient rehabilitation. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Not applicable. RESULTS: Most frequently administered were
      narcotic analgesics (72% of sample), followed by antidepressants (67%),
      anticonvulsants (47%), anxiolytics (33%), hypnotics (30%), stimulants (28%),
      antipsychotics (25%), antiparkinson agents (25%), and miscellaneous psychotropics
      (18%). The psychotropic agents studied were administered to 95% of the sample,
      with 8.5% receiving only 1 and 31.8% receiving >=6. Degree of psychotropic
      medication administration varied widely between sites. Univariate analyses
      indicated younger patients were more likely to receive anxiolytics,
      antidepressants, antiparkinson agents, stimulants, antipsychotics, and narcotic
      analgesics, whereas those older were more likely to receive anticonvulsants and
      miscellaneous psychotropics. Men were more likely to receive antipsychotics. All
      medication classes were less likely administered to Asians and more likely
      administered to those with more severe functional impairment. Use of
      anticonvulsants was associated with having seizures at some point during acute
      care or rehabilitation stays. Narcotic analgesics were more likely for those with
      history of drug abuse, history of anxiety and depression (premorbid or during
      acute care), and severe pain during rehabilitation. Psychotropic medication
      administration increased rather than decreased during the course of inpatient
      rehabilitation in each of the medication categories except for narcotics. This
      observation was also true for medication administration within admission
      functional levels (defined by cognitive FIM scores), except for those with higher
      admission FIM cognitive scores. CONCLUSIONS: Many psychotropic medications are
      used during inpatient rehabilitation. In general, lower admission FIM cognitive
      score groups were administered more of the medications under investigation
      compared with those with higher cognitive function at admission. Considerable
      site variation existed regarding medications administered. The current
      investigation provides baseline data for future studies of effectiveness.

PMID- 26212403
TI  - Predictors of Agitated Behavior During Inpatient Rehabilitation for Traumatic
      Brain Injury.
AB  - OBJECTIVE: To identify predictors of the severity of agitated behavior during
      inpatient traumatic brain injury (TBI) rehabilitation. DESIGN: Prospective,
      longitudinal observational study. SETTING: Inpatient rehabilitation centers.
      PARTICIPANTS: Consecutive patients enrolled between 2008 and 2011, admitted for
      inpatient rehabilitation after index TBI, who exhibited agitation during their
      stay (n=555, N=2130). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE:
      Daytime Agitated Behavior Scale scores. RESULTS: Infection and lower FIM
      cognitive scores predicted more severe agitation. The medication classes
      associated with more severe agitation included sodium channel antagonist
      anticonvulsants, second-generation antipsychotics, and gamma-aminobutyric acid-A
      anxiolytics/hypnotics. Medication classes associated with less severe agitation
      included antiasthmatics, statins, and norepinephrine-dopamine-5 hydroxytryptamine
      (serotonin) agonist stimulants. CONCLUSIONS: Further support is provided for the
      importance of careful serial monitoring of both agitation and cognition to
      provide early indicators of possible beneficial or adverse effects of
      pharmacologic interventions used for any purpose and for giving careful
      consideration to the effects of any intervention on underlying cognition when
      attempting to control agitation. Cognitive functioning was found to predict
      agitation, medications that have been found in previous studies to enhance
      cognition were associated with less agitation, and medications that can
      potentially suppress cognition were associated with more agitation. There could
      be factors other than the interventions that account for these relations. In
      addition, the study provides support for treatment of underlying disorders as a
      possible first step in management of agitation. Although the results of this
      study cannot be used to draw causal inferences, the associations that were found
      can be used to generate hypotheses about the most viable interventions that
      should be tested in future controlled trials.

PMID- 26212404
TI  - Group Therapy Use and Its Impact on the Outcomes of Inpatient Rehabilitation
      After Traumatic Brain Injury: Data From Traumatic Brain Injury-Practice Based
      Evidence Project.
AB  - OBJECTIVES: To describe the amount and content of group therapies provided during
      inpatient rehabilitation for traumatic brain injury (TBI), and to assess the
      relations of group therapy with patient, injury, and treatment factors and
      outcomes. DESIGN: Prospective observational cohort. SETTING: Inpatient
      rehabilitation. PARTICIPANTS: Consecutive admissions (N=2130) for initial TBI
      rehabilitation at 10 inpatient rehabilitation facilities (9 in the United States,
      1 in Canada) from October 2008 to September 2011. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Proportion of sessions that were group therapy (>=2
      patients were treated simultaneously by >=1 clinician); proportion of patients
      receiving group therapy; type of activity performed and amount of time spent in
      group therapy, by discipline; rehabilitation length of stay; discharge location;
      and FIM cognitive and motor scores at discharge. RESULTS: Of the patients, 79%
      received at least 1 session of group therapy, with group therapy accounting for
      13.7% of all therapy sessions and 15.8% of therapy hours. On average, patients
      spent 2.9h/wk in group therapy. The greatest proportion of treatment time in
      group format was in therapeutic recreation (25.6%), followed by speech therapy
      (16.2%), occupational therapy (10.4%), psychology (8.1%), and physical therapy
      (7.9%). Group therapy time and type of treatment activities varied among
      admission FIM cognitive subgroups and treatment sites. Several factors appear to
      be predictive of receiving group therapy, with the treatment site being a major
      influence. However, group therapy as a whole offered little explanation of
      differences in the outcomes studied. CONCLUSIONS: Group therapy is commonly used
      in TBI rehabilitation, to varying degrees among disciplines, sites, and cognitive
      impairment subgroups. Various therapeutic activities take place in group therapy,
      indicating its perceived value in addressing many domains of functioning.
      Variation in outcomes is not explained well by overall percentage of therapy time
      delivered in groups.

PMID- 26212405
TI  - Readmission to an Acute Care Hospital During Inpatient Rehabilitation for
      Traumatic Brain Injury.
AB  - OBJECTIVE: To assess the incidence of, causes for, and factors associated with
      readmission to an acute care hospital (RTAC) during inpatient rehabilitation for
      traumatic brain injury (TBI). DESIGN: Prospective observational cohort. SETTING:
      Inpatient rehabilitation. PARTICIPANTS: Individuals with TBI admitted
      consecutively for inpatient rehabilitation (N=2130). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: RTAC incidence, RTAC causes, rehabilitation
      length of stay (RLOS), and rehabilitation discharge location. RESULTS: A total of
      183 participants (9%) experienced RTAC for a total of 210 episodes. Of 183
      participants, 161 patients experienced 1 RTAC episode, 17 had 2, and 5 had 3. The
      mean time from rehabilitation admission to first RTAC was 22+/-22 days. The mean
      duration in acute care during RTAC was 7+/-8 days. Eighty-four participants (46%)
      had >=1 RTAC episodes for medical reasons, 102 (56%) had >=1 RTAC episodes for
      surgical reasons, and 6 (3%) participants had RTAC episodes for unknown reasons.
      Most common surgical RTAC reasons were neurosurgical (65%), pulmonary (9%),
      infection (5%), and orthopedic (5%); most common medical reasons were infection
      (26%), neurological (23%), and cardiac (12%). Any RTAC was predicted as more
      likely for patients with older age, history of coronary artery disease, history
      of congestive heart failure, acute care diagnosis of depression, craniotomy or
      craniectomy during acute care, and presence of dysphagia at rehabilitation
      admission. RTAC was less likely for patients with higher admission FIM motor
      scores and education less than high school diploma. RTAC occurrence during
      rehabilitation was significantly associated with longer RLOS and smaller
      likelihood of discharge home. CONCLUSIONS: Approximately 9% of patients with TBI
      experienced RTAC episodes during inpatient rehabilitation for various medical and
      surgical reasons. This information may help inform interventions aimed at
      reducing interruptions in rehabilitation for RTAC. RTACs were associated with
      longer RLOS and discharge to an institutional setting.

PMID- 26212406
TI  - Traumatic Brain Injury Patient, Injury, Therapy, and Ancillary Treatments
      Associated With Outcomes at Discharge and 9 Months Postdischarge.
AB  - OBJECTIVE: To examine associations of patient and injury characteristics,
      inpatient rehabilitation therapy activities, and neurotropic medications with
      outcomes at discharge and 9 months postdischarge for patients with traumatic
      brain injury (TBI). DESIGN: Prospective, longitudinal observational study.
      SETTING: Inpatient rehabilitation centers. PARTICIPANTS: Consecutive patients
      (N=2130) enrolled between 2008 and 2011, admitted for inpatient rehabilitation
      after an index TBI injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Rehabilitation length of stay, discharge to home, and FIM at discharge and 9
      months postdischarge. RESULTS: The admission FIM cognitive score was used to
      create 5 relatively homogeneous subgroups for subsequent analysis of treatment
      outcomes. Within each subgroup, significant associations were found between
      outcomes and patient and injury characteristics, time spent in therapy
      activities, and medications used. Patient and injury characteristics explained on
      average 35.7% of the variation in discharge outcomes and 22.3% in 9-month
      outcomes. Adding time spent and level of effort in therapy activities and
      percentage of stay using specific medications explained approximately 20% more
      variation for discharge outcomes and 12.9% for 9-month outcomes. After patient,
      injury, and treatment characteristics were used to predict outcomes, center
      differences added only approximately 1.9% additional variance explained.
      CONCLUSIONS: At discharge, greater effort during therapy sessions, time spent in
      more complex therapy activities, and use of specific medications were associated
      with better outcomes for patients in all admission FIM cognitive subgroups. At 9
      months postdischarge, similar but less pervasive associations were observed for
      therapy activities, but not classes of medications. Further research is warranted
      to examine more specific combinations of therapy activities and medications that
      are associated with better outcomes.

PMID- 26212408
TI  - Synthesis and Multi-Stimuli-Responsive Behavior of Poly(N,N-dimethylaminoethyl
      methacrylate) Spherical Brushes under Different Modes of Confinement in Solution.
AB  - We report the synthesis and solution behavior of photo-, temperature-, pH-, and
      ion-responsive weak polyelectrolyte spherical brushes under different modes of
      confinement. The spherical brushes were prepared by copolymerization of N,N
      dimethylaminoethyl methacrylate (DMAEMA) and 7-(2-methacryloyloxyethoxy)-4
      methylcoumarin anchored to silica nanoparticles via surface-initiated atom
      transfer radical polymerization. The photo-cross-linking and reversibility of the
      nanoparticle-attached coumarin entities are detected by UV-visible spectroscopy
      and dynamic light scattering (DLS). The cross-linking density of poly(DMAEMA)
      (i.e., PDMAEMA) brushes could be easily controlled by alternating irradiation at
      wavelengths of 365 and 254 nm. Moreover, solution behavior under different pH
      levels and ionic strengths is systematically investigated in the PDMAEMA brush
      polyelectrolyte chains confined only by a hard core, the cross-linked PDMAEMA
      brush-polyelectrolyte chains confined by a hard core and cross-linking points,
      and the corresponding hollow nanocapsules after removal of silica by etching
      polyelectrolyte chains confined only by cross-linking points. These three models
      represent the different modes of confinement. DLS results indicate that the
      volume phase transition temperatures of the three models shift to lower
      temperatures with the increase in pH. The highest temperature is afforded to
      phase transition for hollow nanocapsules in solution, followed by the cross
      linked PDMAEMA brushes. The hydrodynamic radius of the polyelectrolyte brush
      systems obviously decreases with the increase in ionic strength of the solution
      when adjusted by NaCl. 

PMID- 26212407
TI  - Rehospitalization During 9 Months After Inpatient Rehabilitation for Traumatic
      Brain Injury.
AB  - OBJECTIVE: To assess the frequency of, causes for, and factors associated with
      acute rehospitalization during 9 months after discharge from inpatient
      rehabilitation for traumatic brain injury (TBI). DESIGN: Multicenter
      observational cohort. SETTING: Community. PARTICIPANTS: Individuals with TBI
      (N=1850) admitted for inpatient rehabilitation. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Occurrences of proxy or self-report of postrehabilitation
      acute care rehospitalization, as well as length of and causes for
      rehospitalizations. RESULTS: A total of 510 participants (28%) had experienced
      775 acute rehospitalizations. All experienced 1 admission (510 participants
      [66%]), whereas 154 (20%) had 2 admissions, 60 (8%) had 3, 23 (3%) had 4, 27 had
      between 5 and 11, and 1 had 12. The most common rehospitalization causes were
      infection (15%), neurological (13%), neurosurgical (11%), injury (7%),
      psychiatric (7%), and orthopedic (7%). The mean time from rehabilitation
      discharge to first rehospitalization was 113 days. The mean rehospitalization
      duration was 6.5 days. Logistic regression analyses revealed that older age,
      history of seizures before injury or during acute care or rehabilitation, history
      of brain injuries, and non-brain injury medical severity increased the risk of
      rehospitalization. Injury etiology of motor vehicle collision and high motor
      functioning at discharge decreased rehospitalization risk. CONCLUSIONS:
      Approximately 28% of patients with TBI were rehospitalized within 9 months of TBI
      rehabilitation discharge owing to various medical and surgical reasons. Future
      research should evaluate whether some of these occurrences may be preventable
      (such as infections, injuries, and psychiatric disorders) and should evaluate the
      extent to which persons at risk may benefit from additional screening,
      surveillance, and treatment protocols.

PMID- 26212409
TI  - Thiyl radicals and induction of protein degradation.
AB  - Thiyl radicals are important intermediates in the redox biology and chemistry of
      thiols. These radicals can react via hydrogen transfer with various C-H bonds in
      peptides and proteins, leading to the generation of carbon-centered radicals,
      and, potentially, to irreversible protein damage. This review summarizes
      quantitative information on reaction kinetics and product formation, and
      discusses the significance of these reactions for protein degradation induced by
      thiyl radical formation. 

PMID- 26212410
TI  - Effects of box handle position and carrying range on bi-manual carrying capacity
      for females.
AB  - This study utilizes a psychophysical approach to examine the effects on carrying
      capacity for bi-manual carrying tasks involving different handle positions and
      carrying ranges. A total of 16 female subjects participated in the experiment in
      groups of two people, and each group of subjects performed the tasks in a random
      order with 12 different combinations of carrying task. The independent variables
      are handle position (upper, middle, lower) and carrying range (F-F: floor height
      carried to floor height, F-W: floor height carried to waist height, W-W: waist
      height carried to waist height, W-F: waist height carried to floor height), the
      dependent variable is the maximum acceptable carried weight (MAWC), heart rate
      (HR), and the rating of perceived exertion (RPE). The results show that the
      handle position has a significant effect on MAWC and overall RPE but no
      significant effect on HR. Carrying range has a significant effect on the MAWC and
      HR, but no significant effect on overall HR. The handle position and carrying
      range have a significant interaction on the MAWC and HR. The RPE for different
      body parts shows significant differences, and the hands feel the most tired.
      Overall, this study confirms that the lower handle position with the W-W carrying
      range is the best combination for a two-person carrying task. 

PMID- 26212411
TI  - Asthma caused by potassium aluminium tetrafluoride: a case series.
AB  - The objective of this study is to describe a case-series of potassium aluminium
      tetrafluoride (KAlF(4))-induced occupational asthma (OA) and/or occupational
      rhinitis (OR). The study involves five patients from a heat-exchanger production
      line who were examined (including specific inhalation challenge tests) for
      suspected OA and/or OR caused by a flux containing almost 100% KAlF(4) - with
      fluorides' workplace air concentrations ranging between 1.7 and 2.8 mg/m(3). No
      subject had a previous history of asthma. All five patients had a positive
      specific challenge test (three patients were diagnosed with OA alone, one with OR
      and one with both OR and OA). At the follow-up visit, after three years on
      average, all patients needed permanent corticosteroid therapy (four topical, one
      oral). After elimination from the exposure, only one of the observed subjects
      gave an indication of an improvement, two subjects stabilized and two worsened.
      Our case series focuses on the correlation between patients' exposure to
      fluorides in air-conditioner production and the subsequent occurrence of OR/OA.
      Currently, it is uncertain whether these OR/OA were caused by hypersensitivity or
      irritation.

PMID- 26212412
TI  - A cross-sectional analysis of dioxins and health effects in municipal and private
      waste incinerator workers in Japan.
AB  - This cross-sectional study was intended to examine health effects of 678 male
      workers employed during an 8-yr period from 2000 to 2007 at 36 municipal and
      private waste incineration plants in Japan. Blood samples were obtained for
      analysis of concentrations of dioxins including coplanar polychlorinated
      biphenyls (coplanar PCBs) and evaluation of health effects. Health effects
      including diabetes were surveyed via a physician's interview or clinical data
      from blood samples. There was a certain difference in serum concentrations of
      polychlorinated dibenzofurans (PCDFs) between the incinerator workers and
      Japanese general population, although no differences in the concentrations of
      total dioxins or polychlorinated dibenzo-p-dioxins (PCDDs) were found between the
      two groups. A few positive correlations between serum levels of PCDDs and PCDFs
      and the results of laboratory and physiological tests were found, but coplanar
      PCBs showed significant relations with 14 parameters of the tests. The background
      serum levels of PCDDs, PCDFs and total dioxins were significantly associated with
      the prevalence of diabetes. No essential differences in serum concentrations of
      total dioxins and in prevalence of diabetes between our subjects and the general
      population suggested that the incinerator workers were marginally exposed to
      dioxins in the workplace without any recognizable adverse health effects. 

PMID- 26212413
TI  - Job stress as a risk factor for absences among manual workers: a 12-month follow
      up study.
AB  - This study was conducted to evaluate the impact of job stress on absence from
      work caused by illnesses and accidents through a prospective research design. A
      total of 2,349 manual workers were included in this analysis. In the first
      survey, job stress was determined using the Korean Occupational Stress Scale
      Short Form. In the second survey, information on absence due to accidents or
      illnesses during the past one year was obtained through a questionnaire. The
      relationship was analyzed using a logistic regression model with multiple
      imputation. After adjusting for confounding variables for males, absence due to
      accidents was statistically associated with high job demand, insufficient job
      control, inadequate social support, and organizational injustice. In addition,
      high job demands and organizational injustice were related to increased absence
      due to illnesses in both genders. A lack of reward was associated with increased
      absence due to illnesses among female workers. We found that job stress was
      associated with a higher risk of absence caused by accidents or illnesses of
      manual workers. 

PMID- 26212414
TI  - Combining expert knowledge and knowledge automatically acquired from electronic
      data sources for continued ontology evaluation and improvement.
AB  - INTRODUCTION: A common bottleneck during ontology evaluation is knowledge
      acquisition from domain experts for gold standard creation. This paper
      contributes a novel semi-automated method for evaluating the concept coverage and
      accuracy of biomedical ontologies by complementing expert knowledge with
      knowledge automatically extracted from clinical practice guidelines and
      electronic health records, which minimizes reliance on expensive domain expertise
      for gold standards generation. METHODS: We developed a bacterial clinical
      infectious diseases ontology (BCIDO) to assist clinical infectious disease
      treatment decision support. Using a semi-automated method we integrated diverse
      knowledge sources, including publically available infectious disease guidelines
      from international repositories, electronic health records, and expert-generated
      infectious disease case scenarios, to generate a compendium of infectious disease
      knowledge and use it to evaluate the accuracy and coverage of BCIDO. RESULTS:
      BCIDO has three classes (i.e., infectious disease, antibiotic, bacteria)
      containing 593 distinct concepts and 2345 distinct concept relationships. Our
      semi-automated method generated an ID knowledge compendium consisting of 637
      concepts and 1554 concept relationships. Overall, BCIDO covered 79% (504/637) of
      the concepts and 89% (1378/1554) of the concept relationships in the ID
      compendium. BCIDO coverage of ID compendium concepts was 92% (121/131) for
      antibiotic, 80% (205/257) for infectious disease, and 72% (178/249) for bacteria.
      The low coverage of bacterial concepts in BCIDO was due to a difference in
      concept granularity between BCIDO and infectious disease guidelines. Guidelines
      and expert generated scenarios were the richest source of ID concepts and
      relationships while patient records provided relatively fewer concepts and
      relationships. CONCLUSIONS: Our semi-automated method was cost-effective for
      generating a useful knowledge compendium with minimal reliance on domain experts.
      This method can be useful for continued development and evaluation of biomedical
      ontologies for better accuracy and coverage.

PMID- 26212415
TI  - Glycation of the high affinity NGF-receptor and RAGE leads to reduced ligand
      affinity.
AB  - AGEs are posttranslational modifications generated by irreversible non-enzymatic
      crosslinking reactions between sugars and proteins - a reaction referred to as
      glycation. Glycation, a feature of ageing, can lead to non-degradable and less
      functional proteins and enzymes and can additionally induce inflammation and
      further pathophysiological processes such as neurodegeneration. In this study we
      investigated the influence of glycation on the high affinity NGF-receptor TrkA
      and the AGE-receptor RAGE. We quantified the binding affinity of the TrkA
      receptor and RAGE to their ligands by surface plasmon resonance (SPR) and
      compared these to the binding affinity after glycation. At the same time, we
      established a glycation procedure using SPR. We found that glycation of TrkA
      reduced the affinity to NGF by a factor of three, which could be shown to lead to
      a reduction of NGF-dependent neurite outgrowth in PC12 cells. Glycation of RAGE
      reduced binding affinity of AGEs by 10-fold. 

PMID- 26212416
TI  - Cocaine-specific neuroplasticity in the ventral striatum network is linked to
      delay discounting and drug relapse.
AB  - AIMS: To contrast functional connectivity on ventral and dorsal striatum networks
      in cocaine dependence relative to pathological gambling, via a resting-state
      functional connectivity approach; and to determine the association between
      cocaine dependence-related neuroadaptations indexed by functional connectivity
      and impulsivity, compulsivity and drug relapse. DESIGN: Cross-sectional study of
      20 individuals with cocaine dependence (CD), 19 individuals with pathological
      gambling (PG) and 21 healthy controls (HC), and a prospective cohort study of 20
      CD followed-up for 12 weeks to measure drug relapse. SETTING AND PARTICIPANTS: CD
      and PG were recruited through consecutive admissions to a public clinic
      specialized in substance addiction treatment (Centro Provincial de
      Drogodependencias) and a public clinic specialized in gambling treatment
      (AGRAJER), respectively; HC were recruited through community advertisement in the
      same area in Granada (Spain). MEASUREMENTS: Seed-based functional connectivity in
      the ventral striatum (ventral caudate and ventral putamen) and dorsal striatum
      (dorsal caudate and dorsal putamen), the Kirby delay-discounting questionnaire,
      the reversal-learning task and a dichotomous measure of cocaine relapse indicated
      with self-report and urine tests. FINDINGS: CD relative to PG exhibit enhanced
      connectivity between the ventral caudate seed and subgenual anterior cingulate
      cortex, the ventral putamen seed and dorsomedial pre-frontal cortex and the
      dorsal putamen seed and insula (P<=0.001, kE=108). Connectivity between the
      ventral caudate seed and subgenual anterior cingulate cortex is associated with
      steeper delay discounting (P<=0.001, kE=108) and cocaine relapse (P<=0.005,
      kE=34). CONCLUSIONS: Cocaine dependence-related neuroadaptations in the ventral
      striatum of the brain network are associated with increased impulsivity and
      higher rate of cocaine relapse.

PMID- 26212418
TI  - Seeking beauty: understanding the psychology behind orthognathic surgery.
AB  - Orthognathic surgery to correct serious skeletal discrepancies of the jaw
      improves both function and appearance, but patients should spend a lot of time
      thinking about, discussing, and planning operations that have such a considerable
      impact. The drive to improve appearance by such radical means is based on social
      and personal reasons, and this must be understood before treatment is considered.
      In this paper, we will review studies on the psychology of orthognathic surgery. 

PMID- 26212417
TI  - Neuroprotection of resveratrol against neurotoxicity induced by methamphetamine
      in mouse mesencephalic dopaminergic neurons.
AB  - Resveratrol is originally extracted from huzhang, a Chinese herbal medicine.
      Recently, resveratrol has attracted a great of attention due to its antioxidant
      and antiapoptotic properties. Although the neuroprotection of resveratrol on
      neural damages in various models has been well characterized, little is known
      about the role of resveratrol in methamphetamine (MA) induced neurotoxicity in
      mesencephalic dopaminergic neurons. Dopaminergic neurons were isolated from
      midbrain of mouse embryos at embryonic day 15 and cultured in the presence of MA
      and resveratrol. Cell viability was examined by MTT assay and the apoptosis was
      assessed using Hoechst33342/PI double staining. To evaluate the Oxidative damage,
      ROS assay was performed. Moreover, the changes of time course of intracellular
      free calcium concentration ([Ca(2+) ]i) were analyzed with Fluo-3/AM tracing. The
      data showed that MA induced the neurotoxicity of cultured cells in a dose
      dependent manner. Resveratrol significantly increased cellular viability and
      retarded cell apoptosis. Furthermore, resveratrol also attenuated MA induced ROS
      production and intracellular free calcium overload. Our results suggest that
      resveratrol protects dopaminergic neurons from MA-induced neuronal cytotoxicity,
      which, at least partly, is mediated by inhibition of [Ca(2+) ]i and oxidative
      stress. (c) 2015 BioFactors 41(4):252-260, 2015. 

PMID- 26212419
TI  - Anterolateral corridor approach to the infratemporal fossa and central skull base
      in maxillectomy: rationale and technical aspects.
AB  - We describe the technical aspects and report our clinical experience of a
      surgical approach to the infratemporal fossa that aims to reduce local recurrence
      after operations for cancer of the posterior maxilla. We tested the technique by
      operating on 3 cadavers and then used the approach in 16 patients who had
      posterolateral maxillectomy for disease that arose on the maxillary alveolus or
      junction of the hard and soft palate (maxillary group), and in 19 who had
      resection of the masticatory compartment and central skull base for advanced
      sinonasal cancer (sinonasal group). Early proximal ligation of the maxillary
      artery was achieved in all but one of the 35 patients. Access to the
      infratemporal fossa enabled division of the pterygoid muscles and pterygoid
      processes under direct vision in all cases. No patient in the maxillary group had
      local recurrence at median follow up of 36 months. Four patients (21%) in the
      sinonasal group had local recurrence at median follow up of 27 months. Secondary
      haemorrhage from the cavernous segment of the internal carotid artery resulted in
      the only perioperative death. The anterolateral corridor approach enables
      controlled resection of tumours that extend into the masticatory compartment. 

PMID- 26212420
TI  - Effect of decompression on cystic lesions of the mandible: 3-dimensional
      volumetric analysis.
AB  - Decompression is effective in reducing both the size of cystic lesions on jaws
      and the associated morbidity of resection. However, quantitative measurement of
      reduced volume after decompression among different cystic diseases has not been
      fully investigated. We have retrospectively investigated the difference in
      reduction in volume among keratocystic odontogenic tumours (n=17), unicystic
      ameloblastomas (n=10), and dentigerous cysts (n=10) of the posterior mandible
      using 3-dimensional computed tomography (CT). Various other influential factors
      such as age, sex, the presence of impacted teeth, and the number of drains were
      also recorded. There was no significant difference in the speed of shrinkage
      among the 3 groups, but there was a significant correlation (p<0.01) between the
      initial detected volume of the lesion and the absolute speed of shrinkage in each
      type of cyst. Initial volume was also significantly associated (p<0.01) with
      reduction of total volume in each type of cyst. Age may correlate negatively with
      the rate of reduction in dentigerous cysts, which means that the older the
      patient is, the less the reduction. Treatment seemed to last longer as the speed
      of shrinkage lessened in the keratocystic tumours and dentigerous cysts (p<0.05)
      as multiple regression has shown. The relative speed of shrinkage of unicystic
      ameloblastomas seemed to be slower when an impacted tooth was involved in the
      lesion (p=0.019). However, the sample size was too small to make any definite
      statistical statement. These results suggest that the rate of reduction of volume
      was related to the original size of the lesion. Despite the need for a second
      operation and longer duration of treatment compared with excision alone,
      decompression is a valuable way of reducing the size of large cystic lesions,
      with low morbidity and recurrence rate. There was no difference in the rate of
      reduction according to the underlying histopathological picture. 

PMID- 26212421
TI  - [Recommendations of the Spanish Paediatric Endocrinology Society Working Group on
      Obesity on eating habits for the prevention of obesity and cardiovascular risk
      factors in childhood].
AB  - Childhood obesity is associated with a high risk of cardiovascular disease and
      early mortality. This paper summarises the currently available evidence on the
      implications of dietary factors on the development and prevention of obesity in
      paediatric patients. Evidence-based recommendations are: promote the consumption
      of slowly absorbed carbohydrates and reduce those with a high-glycaemic-index,
      avoid intake of sugar-sweetened beverages. Fat may provide up to 30-35% of the
      daily energy intake and saturated fat should provide no more than 10% of daily
      energy intake; reduce cholesterol intake, avoid formula milk with a high protein
      content during the first year; promote higher fibre content in the diet, reduce
      sodium intake, and have at least four meals a day, avoiding regular consumption
      of fast food and snacks. 

PMID- 26212422
TI  - [Profiles of cases included in the Spanish registry of patients with alpha-1
      antitrypsin deficiency].

PMID- 26212424
TI  - Editorial: Protection, Repair and Regeneration of Achybreaky Heart.

PMID- 26212423
TI  - Genetic contribution to multiple sclerosis risk among Ashkenazi Jews.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of the central
      nervous system, with a strong genetic component. Over 100 genetic loci have been
      implicated in susceptibility to MS in European populations, the most prominent
      being the 15:01 allele of the HLA-DRB1 gene. The prevalence of MS is high in
      European populations including those of Ashkenazi origin, and low in African and
      Asian populations including those of Jewish origin. METHODS: Here we identified
      and extracted a total of 213 Ashkenazi MS cases and 546 ethnically matched
      healthy control individuals from two previous genome-wide case-control
      association analyses, and 72 trios (affected proband and two unaffected parents)
      from a previous genome-wide transmission disequilibrium association study, using
      genetic data to define Ashkenazi. We compared the pattern of genetic risk between
      Ashkenazi and non-Ashkenazi Europeans. We also sought to identify novel Ashkenazi
      specific risk loci by performing association tests on the subset of Ashkenazi
      cases, controls, probands, and parents from each study. RESULTS: The HLA
      DRB1*15:01 allele and the non-HLA risk alleles were present at relatively low
      frequencies among Ashkenazi and explained a smaller fraction of the population
      level risk when compared to non-Ashkenazi Europeans. Alternative HLA
      susceptibility alleles were identified in an Ashkenazi-only association study,
      including HLA-A*68:02 and one or both genes in the HLA-B*38:01-HLA-C*12:03
      haplotype. The genome-wide screen in Ashkenazi did not reveal any loci associated
      with MS risk. CONCLUSION: These results suggest that genetic susceptibility to MS
      in Ashkenazi Jews has not been as well established as that of non-Ashkenazi
      Europeans. This implies value in studying large well-characterized Ashkenazi
      populations to accelerate gene discovery in complex genetic diseases.

PMID- 26212425
TI  - Pressure-induced dissociation of water molecules in ice VII.
AB  - The neutron diffraction pattern of D2O ice was recently measured at pressures up
      to 52 GPa by Guthrie et al., who proposed an octahedral interstitial model for
      ice at pressures above 13 GPa to account for the deviation of the observed
      crystal structure from that of ice VII. In this article, the octahedral
      interstitial model was re-examined in terms of the interstitial occupancy and X
      ray Raman spectroscopy (XRS) spectra. The interstitial occupancy calculated using
      first-principles molecular dynamics simulations was negligibly small compared to
      that of the interstitial model. The oxygen K-edge spectra calculated for the
      interstitial model exhibited two additional low-energy peaks originating from
      water molecules and hydroxides that are interacting with interstitial protons,
      respectively, whereas these low-energy peaks were not observed in the
      experimentally measured spectra. These results suggest that the interstitial
      model cannot explain the XRS spectra of ice VII at pressures above 13 GPa and
      that more precise structure measurements and analyses are necessary to reveal the
      nature of the pressure-induced transition. 

PMID- 26212426
TI  - ?

PMID- 26212427
TI  - ?

PMID- 26212428
TI  - ?

PMID- 26212430
TI  - ?

PMID- 26212429
TI  - ?

PMID- 26212432
TI  - ?

PMID- 26212431
TI  - ?

PMID- 26212434
TI  - ?

PMID- 26212433
TI  - ?

PMID- 26212435
TI  - Transcriptomic changes during maize roots development responsive to Cadmium (Cd)
      pollution using comparative RNAseq-based approach.
AB  - The heavy metal cadmium (Cd), acts as a widespread environmental contaminant,
      which has shown to adversely affect human health, food safety and ecosystem
      safety in recent years. However, research on how plant respond to various kinds
      of heavy metal stress is scarcely reported, especially for understanding of
      complex molecular regulatory mechanisms and elucidating the gene networks of
      plant respond to Cd stress. Here, transcriptomic changes during Mo17 and B73
      seedlings development responsive to Cd pollution were investigated and
      comparative RNAseq-based approach in both genotypes were performed. 115
      differential expression genes (DEGs) with significant alteration in expression
      were found co-modulated in both genotypes during the maize seedling development;
      of those, most of DGEs were found comprised of stress and defense responses
      proteins, transporters, as well as transcription factors, such as thaumatin-like
      protein, ZmOPR2 and ZmOPR5. More interestingly, genotype-specific transcriptional
      factors changes induced by Cd stress were found contributed to the regulatory
      mechanism of Cd sensitivity in both different genotypes. Moreover, 12 co
      expression modules associated with specific biological processes or pathways (M1
      to M12) were identified by consensus co-expression network. These results will
      expand our understanding of complex molecular mechanism of response and defense
      to Cd exposure in maize seedling roots. 

PMID- 26212436
TI  - Proinflammatory cytokines downregulate connexin 43-gap junctions via the
      ubiquitin-proteasome system in rat spinal astrocytes.
AB  - Astrocytic gap junctions formed by connexin 43 (Cx43) are crucial for
      intercellular communication between spinal cord astrocytes. Various neurological
      disorders are associated with dysfunctional Cx43-gap junctions. However, the
      mechanism modulating Cx43-gap junctions in spinal astrocytes under pathological
      conditions is not entirely clear. A previous study showed that treatment of
      spinal astrocytes in culture with pro-inflammatory cytokines tumor necrosis
      factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) decreased both Cx43
      expression and gap junction intercellular communication (GJIC) via a c-jun N
      terminal kinase (JNK)-dependent pathway. The current study further elaborates the
      intracellular mechanism that decreases Cx43 under an inflammatory condition.
      Cycloheximide chase analysis revealed that TNF-alpha (10 ng/ml) alone or in
      combination with IFN-gamma (5 ng/ml) accelerated the degradation of Cx43 protein
      in cultured spinal astrocytes. The reduction of both Cx43 expression and GJIC
      induced by a mixture of TNF-alpha and IFN-gamma were blocked by pretreatment with
      proteasome inhibitors MG132 (0.5 MUM) and epoxomicin (25 nM), a mixture of TNF
      alpha and IFN-gamma significantly increased proteasome activity and Cx43
      ubiquitination. In addition, TNF-alpha and IFN-gamma-induced activation of
      ubiquitin-proteasome systems was prevented by SP600125, a JNK inhibitor.
      Together, these results indicate that a JNK-dependent ubiquitin-proteasome system
      is induced under an inflammatory condition that disrupts astrocytic gap junction
      expression and function, leading to astrocytic dysfunction and the maintenance of
      the neuroinflammatory state. 

PMID- 26212437
TI  - Partial virological response to entecavir treatment in nucleos(t)ide-naive
      patients with HBeAg-positive chronic hepatitis B is not caused by reduced
      sensitivity.
AB  - Some patients with chronic hepatitis B (CHB) receiving entecavir (ETV) exhibit
      partial virological response (PVR) to ETV and the mechanism is not clear. In this
      study, we aim to investigate the in vitro susceptibility of residual clinical
      strains isolated from the sera of nucleos(t)ide-naive hepatitis B virus e antigen
      (HBeAg)-positive patients with CHB and PVR to ETV, and to evaluate the clinical
      and virological responses to prolonged ETV monotherapy in these patients. We
      followed 69 nucleos(t)ide-naive HBeAg-positive CHB patients receiving ETV
      treatment, with 13 partial responders to ETV. And we found that no genotypic
      resistance mutants were detected among the 13 PVR patients. Phenotypic analysis
      revealed that the residual HBV strains had normal replication capacity, and were
      as susceptible to ETV as wild-type HBV. All PVR patients continued to receive ETV
      monotherapy, and serum HBV DNA of the majority became undetectable after
      prolonged treatment. However, none of these patients achieved HBeAg loss. In
      contrast, 25.6% and 23.2% of the patients with virological response achieved
      HBeAg loss (P < 0.001) and HBeAg seroconversion (P < 0.001) at week 144,
      respectively. Thus, we conclude suboptimal response to ETV might not be due to
      reduced HBV susceptibility to ETV, and prolonging ETV monotherapy in patients
      with PVR is recommended. 

PMID- 26212438
TI  - The yeast chromatin remodeler Rsc1-RSC complex is required for transcriptional
      activation of autophagy-related genes and inhibition of the TORC1 pathway in
      response to nitrogen starvation.
AB  - The yeast RSC, an ATP-dependent chromatin-remodeling complex, is essential for
      mitotic and meiotic growth. There are two distinct isoforms of this complex
      defined by the presence of either Rsc1 or Rsc2; however, the functional
      differences between these complexes are unclear. Here we show that the RSC
      complex containing Rsc1, but not Rsc2, functions in autophagy induction. Rsc1 was
      required not only for full expression of ATG8 mRNA but also for maintenance of
      Atg8 protein stability. Interestingly, decreased autophagic activity and Atg8
      protein stability in rsc1Delta cells, but not the defect in ATG8 mRNA expression,
      were partially suppressed by deletion of TOR1. In addition, we found that
      rsc1Delta impaired the binding between the Rho GTPase Rho1 and the TORC1-specific
      component Kog1, which is required for down-regulation of TORC1 activity. These
      results suggest that the Rsc1-containing RSC complex plays dual roles in the
      proper induction of autophagy: 1) the transcriptional activation of autophagy
      related genes independent of the TORC1 pathway and 2) the inactivation of TORC1,
      possibly through enhancement of Rho1-Kog1 binding. 

PMID- 26212439
TI  - Hypoxia-induced autophagy promotes human prostate stromal cells survival and ER
      stress.
AB  - Benign prostatic hyperplasia (BPH) is emerging as one of the most common diseases
      seriously threatening the health of elderly men. Accumulating evidences indicate
      that hypoxia could induce BPH. However, the underlying mechanism of BPH induced
      by hypoxia is not clear. In the study, hypoxia-induced autophagy could promote
      cell survival and endoplasmic reticula stress (ER stress) in WPMY-1 cells. Cell
      viability induced by hypoxia could been decreased by autophagy inhibitors (3
      methyladenine, bafilomycin A1) or siRNA interference in two autophagy genes
      (Beclin1, ATG5) in WPMY-1 cells. Furthermore, ER stress was present in hypoxia
      treated WPMY-1 cells, while autophagy and cell survival could been inhibited by
      C/EBP-homologous protein siRNA (CHOP), which is an important protein of ER stress
      pathway. Taken together, our data support a novel model that autophagy as a
      cytoprotective response promotes cell survival via ER stress under hypoxia in
      human prostate stromal cells. 

PMID- 26212440
TI  - Kruppel-like factor 2 inhibit the angiogenesis of cultured human liver sinusoidal
      endothelial cells through the ERK1/2 signaling pathway.
AB  - Kruppel-like factor 2 (KLF2) is a crucial anti-angiogenic factor. However, its
      precise role in hepatic angiogenesis induced by liver sinusoidal endothelial
      cells (LSECs) remain unclear. This study was aimed to evaluate the effect of KLF2
      on angiogenesis of LSECs and to explore the corresponding mechanism. Cultured
      human LSECs were infected with different lentiviruses to overexpress or suppress
      KLF2 expression. The CCK-8 assay, transwell migration assay and tube formation
      test, were used to investigate the roles of KLF2 in the proliferation, migration
      and vessel tube formation of LSECs, respectively. The expression and
      phosphorylation of ERK1/2 were detected by western blot. We discovered that the
      up-regulation of KLF2 expression dramatically inhibited proliferation, migration
      and tube formation in treated LSECs. Correspondingly, down-regulation of KLF2
      expression significantly promoted proliferation, migration and tube formation in
      treated LSECs. Additionally, KLF2 inhibited the phosphorylation of ERK1/2
      pathway, followed by the function of KLF2 in the angiogenesis of LSECs disrupted.
      In conclusion, KLF2 suppressed the angiogenesis of LSECs through inhibition of
      cell proliferation, migration, and vessel tube formation. These functions of KLF2
      may be mediated through the ERK1/2 signaling pathway. 

PMID- 26212441
TI  - Laminar shear flow increases hydrogen sulfide and activates a nitric oxide
      producing signaling cascade in endothelial cells.
AB  - Laminar shear flow triggers a signaling cascade that maintains the integrity of
      endothelial cells (ECs). Hydrogen sulfide (H2S), a new gasotransmitter is
      regarded as an upstream regulator of nitric oxide (NO). Whether the H2S
      generating enzymes are correlated to the enzymes involved in NO production under
      shear flow conditions remains unclear as yet. In the present study, the cultured
      ECs were subjected to a constant shear flow (12 dyn/cm(2)) in a parallel flow
      chamber system. We investigated the expression of three key enzymes for H2S
      biosynthesis, cystathionine-gamma-lyase (CSE), cystathionine-beta-synthase (CBS),
      and 3-mercapto-sulfurtransferase (3-MST). Shear flow markedly increased the level
      of 3-MST. Shear flow enhanced the production of H2S was determined by NBD-SCN
      reagent that can bind to cysteine/homocystein. Exogenous treatment of NaHS that
      can release gaseous H2S, ECs showed an increase of phosphorylation in Akt(S473),
      ERK(T202/Y204) and eNOS(S1177). This indicated that H2S can trigger the NO
      production signaling cascade. Silencing of CSE, CBS and 3-MST genes by siRNA
      separately attenuated the phosphorylation levels of Akt(S473) and eNOS(S1177)
      under shear flow conditions. The particular mode of shear flow increased H2S
      production. The interplay between H2S and NO-generating enzymes were discussed in
      the present study. 

PMID- 26212442
TI  - Effects of medium flow on axon growth with or without nerve growth factor.
AB  - Axon growth is a crucial process in regeneration of damaged nerves. On the other
      hand, elongation of nerve fibers in the epidermis has been observed in skin of
      atopic dermatitis patients. Thus, regulation of nerve fiber extension might be an
      effective strategy to accelerate nerve regeneration and/or to reduce itching in
      pruritus dermatosis. We previously demonstrated that neurons and epidermal
      keratinocytes similarly contain multiple receptors that are activated by various
      environmental factors, and in particular, keratinocytes are influenced by shear
      stress. Thus, in the present study, we evaluated the effects of micro-flow of the
      medium on axon growth in the presence or absence of nerve growth factor (NGF),
      using cultured dorsal-root-ganglion (DRG) cells. The apparatus, AXISTM, consists
      of two chambers connected by a set of microgrooves, through which signaling
      molecules and axons, but not living cells, can pass. When DRG cells were present
      in chamber 1, NGF was present in chamber 2, and micro-flow was directed from
      chamber 1 to chamber 2, axon growth was significantly increased compared with
      other conditions. Acceleration of axon growth in the direction of the micro-flow
      was also observed in the absence of NGF. These results suggest that local micro
      flow might significantly influence axon growth. 

PMID- 26212443
TI  - Association between hepatitis B virus and MHC class I polypeptide-related chain A
      in human hepatocytes derived from human-mouse chimeric mouse liver.
AB  - Due to the lack of efficient hepatitis B virus (HBV) infection systems, progress
      in understanding the role of innate immunity in HBV infection has remained
      challenging. Here we used human hepatocytes from a humanized severe combined
      immunodeficiency albumin promoter/enhancer driven-urokinase-type plasminogen
      activator mouse model for HBV infection. HBV DNA levels in culture medium from
      these human hepatocytes were 4.8-5.7 log IU/mL between day 16 and day 66 post
      infection by HBV genotype C inoculum. HBV surface antigen (HBsAg) was also
      detected by chemiluminescent immunoassay from day 7 to day 66 post-infection.
      Western blot analysis revealed that major histocompatibility complex class I
      related chain A (MICA), which plays a role in the innate immune system, was
      induced in HBV-infected human hepatocytes 27 days after infection compared with
      the uninfected control. MICA was reduced at day 62 and undetectable at day 90. Of
      interest, MICA expression by human hepatocytes increased after HBV infection and
      decreased before HBsAg loss. Human hepatocytes derived from chimeric mice with
      hepatocyte-humanized liver could support HBV genome replication. Further studies
      of the association between HBV replication and MICA induction should be
      conducted. 

PMID- 26212444
TI  - Isolation of lipids from biological samples.
AB  - Isolation of the lipid fraction from biological samples has been a crucial part
      of countless studies over the last century. This considerable research interest
      has led to the development of a number of methods for isolating a range of
      molecular species that fall under the umbrella term "lipid". Such methods vary in
      popularity, complexity, specificity and even toxicity. In this review, we explore
      examples of published methods (1952-2014) for isolating lipids from biological
      samples and attempt to assess the limits of techniques both from a chemical and
      biological perspective. We also suggest how a suitable method might be chosen for
      a novel application.

PMID- 26212445
TI  - A revisit on the renin-angiotensin system in cardiovascular biology.

PMID- 26212446
TI  - Relating surface chemistry and oxygen surface exchange in LnBaCo2O(5+delta) air
      electrodes.
AB  - The surface and near-surface chemical composition of electroceramic materials
      often shows significant deviations from that of the bulk. In particular, layered
      materials, such as cation-ordered LnBaCo2O(5+delta) perovskites (Ln =
      lanthanide), undergo surface and sub-surface restructuring due to the segregation
      of the divalent alkaline-earth cation. These processes can take place during
      synthesis and processing steps (e.g. deposition, sintering or annealing), as well
      as at temperatures relevant for the operation of these materials as air
      electrodes in solid oxide fuel cells and electrolysers. Furthermore, the surface
      segregation in these double perovskites shows fast kinetics, starting at
      temperatures as low as 400  degrees C over short periods of time and leading to a
      decrease in the transition metal surface coverage exposed to the gas phase. In
      this work, we use a combination of stable isotope tracer labeling and surface
      sensitive ion beam techniques to study the oxygen transport properties and their
      relationship with the surface chemistry in ordered LnBaCo2O(5+delta) perovskites.
      Time-of-Flight Secondary-Ion Mass Spectrometry (ToF-SIMS) combined with (18)O
      isotope exchange was used to determine the oxygen tracer diffusion (D*) and
      surface exchange (k*) coefficients. Furthermore, Low Energy Ion Scattering (LEIS)
      was used for the analysis of the surface and near surface chemistry as it
      provides information from the first mono-atomic layer of the materials. In this
      way, we could relate the compositional modifications (e.g. cation segregation)
      taking place at the electrochemically-active surface during the exchange at high
      temperatures and the oxygen transport properties in double perovskite electrode
      materials to further our understanding of the mechanism of the surface exchange
      process.

PMID- 26212447
TI  - Malnutrition in Geriatric Rehabilitation: Prevalence, Patient Outcomes, and
      Criterion Validity of the Scored Patient-Generated Subjective Global Assessment
      and the Mini Nutritional Assessment.
AB  - BACKGROUND: Accurate identification and management of malnutrition is essential
      so that patient outcomes can be improved and resources used efficaciously.
      OBJECTIVES: In malnourished older adults admitted to rehabilitation: 1) report
      the prevalence, health and aged care use, and mortality of malnourished older
      adults; 2) determine and compare the criterion (concurrent and predictive)
      validity of the Scored Patient-Generated Subjective Global Assessment (PG-SGA)
      and the Mini Nutritional Assessment (MNA) in diagnosing malnutrition; and 3)
      identify the Scored PG-SGA score cut-off value associated with malnutrition.
      DESIGN: Observational, prospective cohort. PARTICIPANTS/SETTING: Participants
      were 57 older adults (65 years and older; mean+/-standard deviation age=79.1+/
      7.3 years) from two rural rehabilitation units in New South Wales, Australia.
      MEASUREMENTS/STATISTICAL ANALYSIS: Scored PG-SGA; MNA; and the International
      Statistical Classification of Diseases and Health Related Problems, 10th
      revision, Australian Modification (ICD-10-AM) classification of malnutrition were
      compared to establish concurrent validity and report malnutrition prevalence.
      Length of stay, discharge location, rehospitalization, admission to a residential
      aged care facility, and mortality were measured to report health-related outcomes
      and to establish predictive validity. RESULTS: Malnutrition prevalence varied
      according to assessment tool (ICD-10-AM: 46%; Scored PG-SGA: 53%; MNA: 28%).
      Using the ICD-10-AM as the reference standard, the Scored PG-SGA ratings
      (sensitivity 100%, specificity 87%) and score (sensitivity 92%, specificity 84%,
      ROC AUC [receiver operating characteristics area under the curve]=0.910+/-0.038)
      showed strong concurrent validity, and the MNA had moderate concurrent validity
      (sensitivity 58%, specificity 97%, receiver operating characteristics area under
      the curve=0.854+/-0.052). The Scored PG-SGA rating, Scored PG-SGA score, and MNA
      showed good predictive validity. Malnutrition can increase the risk of longer
      rehospitalization length of stay, admission to a residential aged care facility,
      and discharge to hospital or residential aged care facility instead of home.
      CONCLUSIONS: Malnutrition prevalence in the geriatric rural rehabilitation
      population is high, and is associated with increased health and aged care use.
      The Scored PG-SGA ratings and score are suitable for nutrition assessment in
      geriatric rehabilitation. The MNA may be suitable for nutrition assessment in
      geriatric rehabilitation, but care should be taken to ensure all malnourished
      patients are identified. Additional examination of the criterion validity of the
      Scored PG-SGA and MNA will lend confidence to these findings.

PMID- 26212448
TI  - Nutrition Screening in Geriatric Rehabilitation: Criterion (Concurrent and
      Predictive) Validity of the Malnutrition Screening Tool and the Mini Nutritional
      Assessment-Short Form.
AB  - BACKGROUND: Nutrition screening is required for early identification and
      treatment of patients at risk for malnutrition so that clinical outcomes can be
      improved and health care costs reduced. OBJECTIVE: To determine the criterion
      (concurrent and predictive) validity of the Malnutrition Screening Tool (MST) and
      Mini Nutritional Assessment-Short Form (MNA-SF) in older adults admitted to
      inpatient rehabilitation facilities. DESIGN: Observational, prospective cohort.
      PARTICIPANTS/SETTING: Participants were 57 adults aged 65 years and older (mean+/
      standard deviation age=79.1+/-7.3 years) from two rural rehabilitation units in
      New South Wales, Australia. MAIN OUTCOME MEASUREMENTS: MST; MNA-SF; International
      Statistical Classification of Diseases and Health Related Problems, 10th
      revision, Australian Modification (ICD-10-AM) classification of malnutrition;
      rehospitalization; admission to a residential aged care facility
      (institutionalization); and discharge location. STATISTICAL ANALYSIS PERFORMED:
      Measures of diagnostic accuracy with 95% CIs generated from a contingency table,
      Mann-Whitney U test, and chi(2) test. RESULTS: When compared with the ICD-10-AM
      criteria, the MST showed stronger diagnostic accuracy (sensitivity 80.8%,
      specificity 67.7%) than the MNA-SF (sensitivity 100%, specificity 22.6%). Neither
      the MST nor the MNA-SF was able to predict rehospitalization,
      institutionalization, or discharge location. CONCLUSIONS: The MST showed good
      concurrent validity and can be considered an appropriate nutrition screening tool
      in geriatric rehabilitation. The MNA-SF may overestimate the risk of malnutrition
      in this population. The predictive validity could not be established for either
      screening tool.

PMID- 26212449
TI  - Prognostic factors for conditional survival in patients with muscle-invasive
      urothelial carcinoma of the bladder treated with radical cystectomy.
AB  - Because only a few studies have evaluated conditional survival (CS) in bladder
      cancer patients, we examined conditional overall survival (OS) and cancer
      specific survival (CSS) in these patients after radical cystectomy (RC), and
      determined which prognostic variables affect CS over time. We reviewed 487
      patients treated with RC and pelvic lymph node dissection at our institution
      between 1991 and 2012. Cox regression models were used to identify the
      significant prognostic factors for CS depending on clinicopathological
      characteristics. As survival time increased after RC, conditional OS and CSS
      rates increased when compared with baseline survival probability. CS more
      significantly improved in the patients with unfavorable pathologic
      characteristics. While many variables were associated with survival at baseline,
      only age was found to be a significant prognostic factor for 5-year conditional
      OS in all given survivorships. In conclusion, conditional OS and CSS
      probabilities significantly improved over time, with greater improvements in the
      cases with unfavorable pathologic features. Moreover, age remained the key
      prognostic factor for conditional OS estimates from baseline to 5 years after
      surgery. Our results provide practical survival information to guide adjustments
      in our current follow-up strategy for bladder cancer patients after RC. 

PMID- 26212450
TI  - Real-Time Monitoring of Alzheimer's-Related Amyloid Aggregation via Probe
      Enhancement-Fluorescence Correlation Spectroscopy.
AB  - This work describes the use of fluorescence correlation spectroscopy (FCS) and a
      novel amyloid-binding fluorescent probe, ARCAM 1, to monitor the aggregation of
      the Alzheimer's disease-associated amyloid beta-peptide (Abeta). ARCAM 1 exhibits
      a large increase in fluorescence emission upon binding to Abeta assemblies,
      making it an excellent candidate for probe enhancement FCS (PE-FCS). ARCAM 1
      binding does not change Abeta aggregation kinetics. It also exhibits greater
      dynamic range as a probe in reporting aggregate size by FCS in Abeta, when
      compared to thioflavin T (ThT) or an Abeta peptide modified with a fluorophore.
      Using fluorescent burst analysis (via PE-FCS) to follow aggregation of Abeta, we
      detected soluble aggregates at significantly earlier time points compared to
      typical bulk fluorescence measurements. Autocorrelation analysis revealed the
      size of these early Abeta assemblies. These results indicate that PE-FCS/ARCAM 1
      based assays can detect and provide size characterization of small Abeta
      aggregation intermediates during the assembly process, which could enable
      monitoring and study of such aggregates that transiently accumulate in biofluids
      of patients with Alzheimer's and other neurodegenerative diseases. 

PMID- 26212455
TI  - Krimper Enforces an Antisense Bias on piRNA Pools by Binding AGO3 in the
      Drosophila Germline.
AB  - Piwi-interacting RNAs (piRNAs) suppress transposon activity in animal germ cells.
      In the Drosophila ovary, primary Aubergine (Aub)-bound antisense piRNAs initiate
      the ping-pong cycle to produce secondary AGO3-bound sense piRNAs. This increases
      the number of secondary Aub-bound antisense piRNAs that can act to destroy
      transposon mRNAs. Here we show that Krimper (Krimp), a Tudor-domain protein,
      directly interacts with piRNA-free AGO3 to promote symmetrical dimethylarginine
      (sDMA) modification, ensuring sense piRNA-loading onto sDMA-modified AGO3. In aub
      mutant ovaries, AGO3 associates with ping-pong signature piRNAs, suggesting
      AGO3's compatibility with primary piRNA loading. Krimp sequesters ectopically
      expressed AGO3 within Krimp bodies in cultured ovarian somatic cells (OSCs), in
      which only the primary piRNA pathway operates. Upon krimp-RNAi in OSCs, AGO3
      loads with piRNAs, further showing the capacity of AGO3 for primary piRNA
      loading. We propose that Krimp enforces an antisense bias on piRNA pools by
      binding AGO3 and blocking its access to primary piRNAs. 

PMID- 26212453
TI  - An Interactive Database for the Assessment of Histone Antibody Specificity.
AB  - Access to high-quality antibodies is a necessity for the study of histones and
      their posttranslational modifications (PTMs). Here we debut the Histone Antibody
      Specificity Database (http://www.histoneantibodies.com), an online and expanding
      resource cataloging the behavior of widely used, commercially available histone
      antibodies by peptide microarray. This interactive web portal provides a critical
      resource to the biological research community that routinely uses these
      antibodies as detection reagents for a wide range of applications. 

PMID- 26212454
TI  - Structural Mechanisms of Nucleosome Recognition by Linker Histones.
AB  - Linker histones bind to the nucleosome and regulate the structure of chromatin
      and gene expression. Despite more than three decades of effort, the structural
      basis of nucleosome recognition by linker histones remains elusive. Here, we
      report the crystal structure of the globular domain of chicken linker histone H5
      in complex with the nucleosome at 3.5 A resolution, which is validated using
      nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of
      the nucleosome and interacts with both DNA linkers. Our structure integrates
      results from mutation analyses and previous cross-linking and fluorescence
      recovery after photobleach experiments, and it helps resolve the long debate on
      structural mechanisms of nucleosome recognition by linker histones. The on-dyad
      binding mode of the H5 globular domain is different from the recently reported
      off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker
      histones with different binding modes could fold chromatin to form distinct
      higher-order structures. 

PMID- 26212456
TI  - Conformational Differences between Open and Closed States of the Eukaryotic
      Translation Initiation Complex.
AB  - Translation initiation in eukaryotes begins with the formation of a pre
      initiation complex (PIC) containing the 40S ribosomal subunit, eIF1, eIF1A, eIF3,
      ternary complex (eIF2-GTP-Met-tRNAi), and eIF5. The PIC, in an open conformation,
      attaches to the 5' end of the mRNA and scans to locate the start codon, whereupon
      it closes to arrest scanning. We present single particle cryo-electron microscopy
      (cryo-EM) reconstructions of 48S PICs from yeast in these open and closed states,
      at 6.0 A and 4.9 A, respectively. These reconstructions show eIF2beta as well as
      a configuration of eIF3 that appears to encircle the 40S, occupying part of the
      subunit interface. Comparison of the complexes reveals a large conformational
      change in the 40S head from an open mRNA latch conformation to a closed one that
      constricts the mRNA entry channel and narrows the P site to enclose tRNAi, thus
      elucidating key events in start codon recognition.

PMID- 26212457
TI  - Division of Labor in an Oligomer of the DEAD-Box RNA Helicase Ded1p.
AB  - Most aspects of RNA metabolism involve DEAD-box RNA helicases, enzymes that bind
      and remodel RNA and RNA-protein complexes in an ATP-dependent manner. Here we
      show that the DEAD-box helicase Ded1p oligomerizes in the cell and in vitro, and
      unwinds RNA as a trimer. Two protomers bind the single-stranded region of RNA
      substrates and load a third protomer to the duplex, which then separates the
      strands. ATP utilization differs between the strand-separating protomer and those
      bound to the single-stranded region. Binding of the eukaryotic initiation factor
      4G to Ded1p interferes with oligomerization and thereby modulates unwinding
      activity and RNA affinity of the helicase. Our data reveal a strict division of
      labor between the Ded1p protomers in the oligomer. This mode of oligomerization
      fundamentally differs from other helicases. Oligomerization represents a
      previously unappreciated level of regulation for DEAD-box helicase activities. 

PMID- 26212458
TI  - The Mismatch-Binding Factor MutSbeta Can Mediate ATR Activation in Response to
      DNA Double-Strand Breaks.
AB  - Ataxia telangiectasia-mutated and Rad3-related (ATR) protein kinase, a master
      regulator of DNA-damage response, is activated by RPA-coated single-stranded DNA
      (ssDNA) generated at stalled replication forks or DNA double-strand breaks
      (DSBs). Here, we identify the mismatch-binding protein MutSbeta, a heterodimer of
      MSH2 and MSH3, as a key player in this process. MSH2 and MSH3 form a complex with
      ATR and its regulatory partner ATRIP, and their depletion compromises the
      formation of ATRIP foci and phosphorylation of ATR substrates in cells responding
      to replication-associated DSBs. Purified MutSbeta binds to hairpin loop
      structures that persist in RPA-ssDNA complexes and promotes ATRIP recruitment.
      Mutations in the mismatch-binding domain of MSH3 abolish the binding of MutSbeta
      to DNA hairpin loops and its ability to promote ATR activation by ssDNA. These
      results suggest that hairpin loops might form in ssDNA generated at sites of DNA
      damage and trigger ATR activation in a process mediated by MutSbeta. 

PMID- 26212459
TI  - Repression of the Heat Shock Response Is a Programmed Event at the Onset of
      Reproduction.
AB  - The heat shock response (HSR) is essential for proteostasis and cellular health.
      In metazoans, aging is associated with a decline in quality control, thus
      increasing the risk for protein conformational disease. Here, we show that in C.
      elegans, the HSR declines precipitously over a 4 hr period in early adulthood
      coincident with the onset of reproductive maturity. Repression of the HSR occurs
      due to an increase in H3K27me3 marks at stress gene loci, the timing of which is
      determined by reduced expression of the H3K27 demethylase jmjd-3.1. This results
      in a repressed chromatin state that interferes with HSF-1 binding and suppresses
      transcription initiation in response to stress. The removal of germline stem
      cells preserves jmjd-3.1 expression, suppresses the accumulation of H3K27me3 at
      stress gene loci, and maintains the HSR. These findings suggest that competing
      requirements of the germline and soma dictate organismal stress resistance as
      animals begin reproduction. 

PMID- 26212460
TI  - The outcome of acute respiratory distress syndrome in relation to body mass index
      and diabetes mellitus.
AB  - OBJECTIVE: To determine the 28 day mortality of patients with ARDS in relation to
      body mass index (BMI) and presence diabetes mellitus (DM). DESIGN: Retrospective
      cohort study of patients enrolled in the ARDS Network randomized controlled
      trials. RESULTS: 2914 patients were enrolled in these trials. 112 patients were
      underweight (BMI < 18.5), 948 patients were normal range (18.5 <= BMI < 25.0),
      801 patients were overweight (25.0 <= BMI < 30.0), 687 patients were obese (30.0
      <= BMI < 40.0), and 175 patients were severely obese (BMI >= 40.0). 469 patients
      had DM. There was no significant difference in the 28 day mortality in relation
      to BMI or presence of DM (underweight adjusted OR, 1.217; 95% CI, 0.749-1.979;
      overweight adjusted OR, 0.887; 95% CI, 0.696-1.131; obese adjusted OR, 0.812; 95%
      CI, 0.624-1.056; severely obese adjusted OR, 1.102; 95% CI, 0.716-1.695; and DM
      adjusted OR, 0.938; 95% CI, 0.728-1.208). CONCLUSIONS: The short term mortality
      in patients with ARDS is not affected by BMI or the presence of DM.

PMID- 26212461
TI  - Handgrip strength as a predictor of bone mineral density in outpatients with
      cirrhosis.
AB  - BACKGROUND AND AIM: Osteoporosis is well recognized as a cirrhosis complication;
      however, most studies assessing this condition included only patients on liver
      transplantation lists with an elevated rate of bone diseases. While general
      population studies show that handgrip strength is clearly associated with bone
      mineral density, until now this tool has not been applied to patients with
      cirrhosis in relation to their bone condition. This study aimed to evaluate
      whether handgrip strength, bone, and liver tests may be useful as predictors of
      bone disease in outpatients with cirrhosis. METHODS: One hundred twenty-nine
      subjects were included (77 men and 52 women). Dual-energy X-ray absorptiometry
      was applied to evaluate lumbar-spine and femoral-neck T scores.
      Osteoporosis/osteopenia rates were 26.3%/35.6% in the lumbar spine and 6.9%/41.8%
      in the femoral neck, respectively. Model selections were based on backward
      procedures to find the best predictors of low T scores. RESULTS: For lumbar
      spine, only low handgrip strength and high parathyroid hormone levels were
      clearly related to low T scores. For femoral neck, only age was associated with
      low T scores. CONCLUSIONS: Handgrip strength may serve as an effective predictor
      of low lumbar spine T score among outpatients with cirrhosis. As cirrhosis
      affects the lumbar spine more than the femoral neck, these results suggest that
      handgrip strength should be tested in all patients with cirrhosis as a first
      indicator of bone health.

PMID- 26212462
TI  - Droplet-Shooting and Size-Filtration (DSSF) Method for Synthesis of Cell-Sized
      Liposomes with Controlled Lipid Compositions.
AB  - We report a centrifugal microfluidic method, droplet-shooting and size-filtration
      (DSSF), for the production of cell-sized liposomes with controlled lipid
      compositions. This involves the generation of large and small droplets from the
      tip of a glass capillary and the selective transfer of small droplets through an
      oil-water interface, thus resulting in the generation of cell-sized liposomes. We
      demonstrate control of the microdomain formation as well as the formation of
      asymmetric lipid bilayer liposomes of uniform size by the control of lipid
      composition. The DSSF method involves simple microfluidics and is easy to use. In
      addition, only a small volume (0.5-2 MUL) of sample solution is required for the
      formation of hundreds of cell-sized liposomes. We believe that this method can be
      applied to generate cell-sized liposomes for a wide variety of uses, such as the
      construction of artificial cell-like systems. 

PMID- 26212463
TI  - Realistic affective forecasting: The role of personality.
AB  - Affective forecasting often drives decision-making. Although affective
      forecasting research has often focused on identifying sources of error at the
      event level, the present investigation draws upon the "realistic paradigm" in
      seeking to identify factors that similarly influence predicted and actual
      emotions, explaining their concordance across individuals. We hypothesised that
      the personality traits neuroticism and extraversion would account for variation
      in both predicted and actual emotional reactions to a wide array of stimuli and
      events (football games, an election, Valentine's Day, birthdays, happy/sad film
      clips, and an intrusive interview). As hypothesised, individuals who were more
      introverted and neurotic anticipated, correctly, that they would experience
      relatively more unpleasant emotional reactions, and those who were more
      extraverted and less neurotic anticipated, correctly, that they would experience
      relatively more pleasant emotional reactions. Personality explained 30% of the
      concordance between predicted and actual emotional reactions. Findings suggest
      three purported personality processes implicated in affective forecasting,
      highlight the importance of individual-differences research in this domain, and
      call for more research on realistic affective forecasts.

PMID- 26212465
TI  - Understanding Insulin Pump Therapy.
AB  - It is estimated that 375,000 Americans are utilizing insulin pump therapy to
      manage their diabetes. This article will educate community health care nurses
      regarding use of the insulin pump, and how to operate special settings for more
      effective glycemic control. Complications of pump therapy, as well as
      hyperglycemia, are not always avoidable; however, interventions are in place to
      prevent and treat complications. Furthermore, important assessment questions are
      employed to assist community health nurses in evaluating the patient knowledge
      base and management skills of their disease process in hyperglycemic episodes and
      emergency situations. 

PMID- 26212464
TI  - Multidimensional Model of Disability and Role Functioning in Rheumatoid
      Arthritis.
AB  - OBJECTIVE: To examine a model addressing the roles of rheumatoid arthritis (RA)
      disease burden, mood disturbance, and disability as determinants of impairments
      in role functioning. METHODS: In a cross-sectional design, 103 RA patients
      recruited from the community to participate in a clinical trial completed
      assessments of self-assessed disease burden (total joint pain and disease
      activity), mood disturbance (Center for Epidemiological Studies Depression Scale
      depressed mood, somatic symptoms, lack of positive affect, and interpersonal
      problems), disability (Health Assessment Questionnaire disability index gross and
      fine motor), and role functioning (Short Form 36 health survey physical and
      social). Structural equation modeling (SEM) was used to examine direct and
      indirect mechanisms linking disease burden to role functioning. RESULTS: SEM
      results indicated that the model had excellent fit: S-Bchi(2)(30) = 38.59, P =
      0.135; comparative fit index = 0.977, standardized root mean residual = 0.062,
      and root mean square error of approximation = 0.053. Mediational analyses
      demonstrated that, while disease burden was associated with poor role
      functioning, its effects were jointly mediated by mood disturbance and
      disability. After the effects of mood disturbance and disability were taken into
      account, the effect of disease burden on role functioning was not significant.
      CONCLUSION: The results indicate that mood disturbance and disability may serve
      as important pathways through which RA disease burden affects role functioning.
      Future longitudinal research is suggested to replicate these findings and further
      explore the mediational mechanisms examined in this study.

PMID- 26212466
TI  - Coalition Building for Health: A Community Garden Pilot Project with Apartment
      Dwelling Refugees.
AB  - Refugees often experience compromised health from both pre- and post-migration
      stressors. Coalition theory has helped guide the development of targeted programs
      to address the health care needs of vulnerable populations. Using the Community
      Coalition Action Theory as a framework, a coalition was formed to implement a
      community garden with apartment-dwelling refugees. Outcomes included successful
      coalition formation, a community garden, reported satisfaction from all gardeners
      with increased vegetable intake, access to culturally meaningful foods, and
      evidence of increased community engagement. The opportunity for community health
      nurses to convene a coalition to affect positive health for refugees is
      demonstrated.

PMID- 26212467
TI  - Community Collaboration in Caring for Students with Diabetes: A Case Study.
AB  - This case study highlights the collaborative efforts of three institutions in a
      community to implement one component of a state law requiring school districts to
      observe specific guidelines for management of students with diabetes. Individuals
      in the school system, the local university, and the regional medical center
      pooled resources to meet the specific requirements. Collaboration is a reasonable
      and cost-effective strategy for other systems that may be seeking ways to
      implement similar statutes. This case study provides a model for collaborative
      practice that highlights the potential for community partnerships, while
      acknowledging the challenges involved with implementing the statute. 

PMID- 26212468
TI  - Assessing Impact of Community Health Nurses on Improving Primary Care Use by
      Homeless/Marginally Housed Persons.
AB  - This study invited a cross-sectional sample of 112 homeless/marginally housed
      adults in New Haven, CT to respond to a structured survey questionnaire. Seventy
      six individuals responded. Among them, 39 (51%) had utilized primary care
      services during the preceding 2 years. Multivariate logistic regression analysis
      adjusting for age, sex, ethnicity, housing status, health insurance status, and
      self-reported health status found that having utilized primary care services was
      significantly associated with having regular contact with a community health
      nurse. This finding indicates that community health nurses may have a significant
      influence in increasing primary care service utilization by homeless and
      marginally housed individuals. 

PMID- 26212470
TI  - Low-grade salivary duct carcinoma in the bronchus.

PMID- 26212472
TI  - Creating sigma-holes through the formation of beryllium bonds.
AB  - Through the use of ab initio theoretical models based on MP2/aug-cc-pVDZ
      optimized geometries and CCSD(T)/aug-cc-pVTZ and CCSD(T)/aug-c-pVDZ total
      energies, it has been shown that the significant electron density rearrangements
      that follow the formation of a beryllium bond may lead to the appearance of a
      sigma-hole in systems that previously do not exhibit this feature, such as CH3
      OF, NO2 F, NO3 F, and other fluorine-containing systems. The creation of the
      sigma-hole is another manifestation of the bond activation-reinforcement (BAR)
      rule. The appearance of a sigma-hole on the F atoms of CH3 OF is due to the
      enhancement of the electronegativity of the O atom that participates in the
      beryllium bond. This atom recovers part of the charge transferred to Be by
      polarizing the valence density of the F into the bonding region. An analysis of
      the electron density shows that indeed this bond becomes reinforced, but the F
      atom becomes more electron deficient with the appearance of the sigma-hole.
      Importantly, similar effects are also observed even when the atom participating
      in the beryllium bond is not directly attached to the F atom, as in NO2 F, NO3 F,
      or NCF. Hence, whereas the isolated CH3 OF, NO2 F, and NO3 F are unable to yield
      F???Base halogen bonds, their complexes with BeX2 derivatives are able to yield
      such bonds. Significant cooperative effects between the new halogen bond and the
      beryllium bond reinforce the strength of both noncovalent interactions. 

PMID- 26212471
TI  - PanGen-Fam: Spanish registry of hereditary pancreatic cancer.
AB  - PURPOSE: To describe the organisation of the registry and the preliminary results
      in terms of characteristics of high-risk pancreatic ductal adenocarcinoma (PDAC)
      families recruited to date and findings of the screening programme. To compare
      early onset sporadic cases (?50 years), sporadic cases (>50 years) and cases with
      family history of cancer, for PDAC possible risk factors. METHODS/PATIENTS:
      Families with hereditary cancer syndromes predisposing to PDAC were recruited
      from two main sources: Spanish hospitals participating in PanGenEU, a pan
      European multicentre case-control study, and their genetic counseling unit.
      Individuals at high-risk of PDAC were enrolled into a screening programme,
      consisting of Endoscopic ultrasound, computerised tomography, magnetic resonance
      imaging. Genetic testing of candidate genes was offered according to each
      patient's risk. RESULTS: Among 577 consecutive PDAC cases, recruited via
      PanGenEU, 36 (6%) had ?2 first-degree relative with PDAC: Familial pancreatic
      cancer (FPC). So far PanGen-Fam has recruited 42 high-risk PDAC families; 25
      (60%) had FPC. Five index cases with cancer were positive for BRCA2 and one for
      BRCA1 germline mutations. In the second year of prospective PDAC screening, one
      neuroendocrine tumour and a high-grade dysplasia lesion suspicious of carcinoma
      were diagnosed among 41 high-risk individuals. Furthermore EUS detected chronic
      pancreatitis-like parenchymal changes in 15 patients. CONCLUDING STATEMENT: The
      identification and recruitment of PDAC high-risk families into the PanGen-Fam
      registry provides an opportunity to detect early onset cancer and precursor
      pancreatic cancer lesions at a potentially curative stage and to increase the
      knowledge of the natural history of the disease.

PMID- 26212473
TI  - A Rapid and Efficient Method for Evaluation of Suspect Testimony: Palynological
      Scanning.
AB  - A rapid method for evaluating suspect testimony is valuable at any stage in an
      inquiry and can result in a change of direction in an investigation. Rape cases,
      in particular, can present problems where a defendant renders DNA analysis
      redundant by claiming that the claimant consented to have sexual relations.
      Forensic palynology is valuable in confirming or eliminating locations as being
      crime scenes, thus checking the testimony of both parties. In contrast to some
      forensic disciplines, forensic palynology can provide critical information
      without time-consuming full analysis. Two cases are described where the
      palynological assemblages from comparator samples of pertinent places were
      compared with those obtained from clothing of claimants and defendants. The
      results of rapid microscopical scanning of relevant preparations led to early
      confessions, thus obviating the need for costly analyses and protracted court
      proceedings. A third case demonstrates the unbiased nature of this technique
      where a man, although innocent of any offense, lied about having visited the
      crime scene for fear of prosecution. This highlights the need for sensitive
      policing in claims of rape.

PMID- 26212474
TI  - Poly(vinyl sulfonate) Facilitates bFGF-Induced Cell Proliferation.
AB  - Heparin is a highly sulfated polysaccharide and is useful because of its diverse
      biological functions. However, because of batch-to-batch variability and other
      factors, there is significant interest in preparing biomimetics of heparin. To
      identify polymeric heparin mimetics, a cell-based screening assay was developed
      in cells that express fibroblast growth factor receptors (FGFRs) but not heparan
      sulfate proteoglycans. Various sulfated and sulfonated polymers were screened,
      and poly(vinyl sulfonate) (pVS) was identified as the strongest heparin-mimicking
      polymer in its ability to enhance binding of basic fibroblast growth factor
      (bFGF) to FGFR. The results were confirmed by an ELISA-based receptor-binding
      assay. Different molecular weights of pVS polymer were synthesized by reversible
      addition-fragmentation chain transfer (RAFT) polymerization. The polymers were
      able to facilitate dimerization of FGFRs leading to cell proliferation in FGFR
      expressing cells, and no size dependence was observed. The data showed that pVS
      is comparable to heparin in these assays. In addition, pVS was not cytotoxic to
      fibroblast cells up to at least 1 mg/mL. Together this data indicates that pVS
      should be explored further as a replacement for heparin. 

PMID- 26212475
TI  - A cross-priming amplification assay coupled with vertical flow visualization for
      detection of Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus is a marine seafood-borne pathogen that causes
      gastrointestinal disorders in humans. In this study, we developed a cross-priming
      amplification (CPA) assay coupled with vertical flow (VF) visualization for rapid
      and sensitive detection of V. parahaemolyticus. This assay correctly detected all
      target strains (n = 13) and none of the non-target strains (n = 27). Small
      concentrations of V. parahaemolyticus (1.8 CFU/mL for pure cultures and 18 CFU/g
      for reconstituted samples) were detected within 1 h. CPA-VF can be applied at a
      large scale and can be used to detect V. parahaemolyticus strains rapidly in
      seafood and environmental samples, being especially useful in the field.

PMID- 26212476
TI  - Gene silencing by RNA interference in the house dust mite, Dermatophagoides
      pteronyssinus.
AB  - This is the first report of gene silencing by RNA interference (RNAi) in the
      European house dust mite, Dermatophagoides pteronyssinus, Trouessart, 1897. Using
      a non-invasive immersion method first developed for the honey bee mite, Varroa
      destructor, a significant reduction in the expression of D. pteronyssinus
      glutathione-S-transferase mu-class 1 enzyme (DpGST-mu1) was achieved following
      overnight immersion in double stranded RNA encoding DpGST-mu1. Although no
      detrimental phenotypic changes were observed following silencing, this technique
      can now be used to address fundamental physiological questions and assess the
      potential therapeutic benefit in silencing D. pteronyssinus target genes in
      selected domestic situations of high human-mite interface. 

PMID- 26212477
TI  - A literature-driven method to calculate similarities among diseases.
AB  - BACKGROUND: "Our lives are connected by a thousand invisible threads and along
      these sympathetic fibers, our actions run as causes and return to us as results".
      It is Herman Melville's famous quote describing connections among human lives. To
      paraphrase the Melville's quote, diseases are connected by many functional
      threads and along these sympathetic fibers, diseases run as causes and return as
      results. The Melville's quote explains the reason for researching disease-disease
      similarity and disease network. Measuring similarities between diseases and
      constructing disease network can play an important role in disease function
      research and in disease treatment. To estimate disease-disease similarities, we
      proposed a novel literature-based method. METHODS AND RESULTS: The proposed
      method extracted disease-gene relations and disease-drug relations from
      literature and used the frequencies of occurrence of the relations as features to
      calculate similarities among diseases. We also constructed disease network with
      top-ranking disease pairs from our method. The proposed method discovered a
      larger number of answer disease pairs than other comparable methods and showed
      the lowest p-value. CONCLUSIONS: We presume that our method showed good results
      because of using literature data, using all possible gene symbols and drug names
      for features of a disease, and determining feature values of diseases with the
      frequencies of co-occurrence of two entities. The disease-disease similarities
      from the proposed method can be used in computational biology researches which
      use similarities among diseases.

PMID- 26212478
TI  - A long war begins: biosimilars versus patented biologics.

PMID- 26212479
TI  - Health state utility values associated with advanced gastric, oesophageal, or
      gastro-oesophageal junction adenocarcinoma: a systematic review.
AB  - OBJECTIVES: To systematically identify utility values associated with advanced
      gastric cancer (GC), oesophageal cancer (OC), or gastro-oesophageal junction
      (GEJ) cancer. Utility values relating to health states are an essential component
      for cost-utility analysis (CUA). METHODS: MEDLINE, Embase, Cochrane Library, and
      EconLit databases were reviewed for relevant studies using a pre-defined search
      strategy. Studies eligible for inclusion reported health state utility values
      (HSUVs) using direct (standard gamble [SG] and time-trade-off [TTO]) and indirect
      (such as EuroQol 5D [EQ-5D], short-form 6D [SF-6D], and the 15-dimensional
      instrument [15D]) methods for patients with advanced GC, OC, or GEJ cancer.
      RESULTS: A total of 539 unique publications were identified, of which eight met
      the inclusion criteria (GC, n = 2; mixed population [gastrointestinal cancers], n
      = 4; OC, n =  ). The most commonly used instrument to estimate HSUVs was the EQ
      5D (n = 7). Utilities were also estimated using the SF-6D and the 15D in the same
      study (n = 1). Direct elicitation methods included the TTO (n = 2) and SG (n =
      1). Across the eight identified publications, health states and study populations
      were heterogeneous and sample sizes were limited. LIMITATIONS: This review, as
      with all summaries of this nature, is only as robust as the data derived from the
      identified studies. The systematic review process does not resolve any design
      issues or biases associated with the original studies. CONCLUSIONS: Limited data
      estimate HSUVs in patients with advanced GC, OC, or GEJ cancer. Utilities for
      advanced GC alone and advanced OC alone were reported in only two publications
      for each cancer type. No publications considered advanced GEJ utilities alone,
      and four publications considered utilities for a mixed population of
      gastrointestinal cancer types. Comparisons are confounded by heterogeneity across
      the identified publications. Further research into HSUVs associated with advanced
      GC and OC is required to improve the evidence available for use in CUAs.

PMID- 26212480
TI  - Reply: Re: Cost-effectiveness of continuous subcutaneous apomorphine in the
      treatment of Parkinson's Disease in the UK and Germany.

PMID- 26212481
TI  - Acid-Labile Thermoresponsive Copolymers That Combine Fast pH-Triggered Hydrolysis
      and High Stability under Neutral Conditions.
AB  - Biodegradable polymeric materials are intensively used in biomedical
      applications. Of particular interest for drug-delivery applications are polymers
      that are stable at pH 7.4, that is, in the blood stream, but rapidly hydrolyze
      under acidic conditions, such as those encountered in the endo/lysosome or the
      tumor microenvironment. However, an increase in the acidic-degradation rate of
      acid-labile groups goes hand in hand with higher instability of the polymer at pH
      7.4 or during storage, thus posing an intrinsic limitation on fast degradation
      under acidic conditions. Herein, we report that a combination of acid-labile
      dimethyldioxolane side chains and hydroxyethyl side chains leads to acid
      degradable thermoresponsive polymers that are quickly hydrolyzed under slightly
      acidic conditions but stable at pH 7.4 or during storage. We ascribe these
      properties to high hydration of the hydroxy-containing collapsed polymer globules
      in conjunction with autocatalytic acceleration of the hydrolysis reactions by the
      hydroxy groups.

PMID- 26212482
TI  - VaccineDA: Prediction, design and genome-wide screening of oligodeoxynucleotide
      based vaccine adjuvants.
AB  - Immunomodulatory oligodeoxynucleotides (IMODNs) are the short DNA sequences that
      activate the innate immune system via toll-like receptor 9. These sequences
      predominantly contain unmethylated CpG motifs. In this work, we describe
      VaccineDA (Vaccine DNA adjuvants), a web-based resource developed to design IMODN
      based vaccine adjuvants. We collected and analyzed 2193 experimentally validated
      IMODNs obtained from the literature. Certain types of nucleotides (e.g., T, GT,
      TC, TT, CGT, TCG, TTT) are dominant in IMODNs. Based on these observations, we
      developed support vector machine-based models to predict IMODNs using various
      compositions. The developed models achieved the maximum Matthews Correlation
      Coefficient (MCC) of 0.75 with an accuracy of 87.57% using the pentanucleotide
      composition. The integration of motif information further improved the
      performance of our model from the MCC of 0.75 to 0.77. Similarly, models were
      developed to predict palindromic IMODNs and attained a maximum MCC of 0.84 with
      the accuracy of 91.94%. These models were evaluated using a five-fold cross
      validation technique as well as validated on an independent dataset. The models
      developed in this study were integrated into VaccineDA to provide a wide range of
      services that facilitate the design of DNA-based vaccine adjuvants
      (http://crdd.osdd.net/raghava/vaccineda/). 

PMID- 26212483
TI  - Palladium-Catalyzed Hydroamidocarbonylation of Olefins to Imides.
AB  - Carbonylation reactions allow the efficient synthesis of all kinds of carbonyl
      containing compounds. Here, we report a straightforward synthesis of various
      imides from olefins and CO for the first time. The established
      hydroamidocarbonylation reaction affords imides in good yields (up to 90 %) and
      with good regioselectivity (up to 99:1) when applying different alkenes and
      amides. The synthetic potential of the method is highlighted by the synthesis of
      Aniracetam by intramolecular hydroamidocarbonylation. 

PMID- 26212484
TI  - Factors Associated with Recurrent Suicidal Ideation among Racially and Ethnically
      Diverse College Students with a History of Suicide Attempt: The Role of
      Mindfulness.
AB  - Although one-third of enrolled U.S. undergraduate college students are non-White,
      little is known about risk factors for suicidal behavior among racial and ethnic
      minority students. Thus, we set out to determine psychosocial factors associated
      with recurrent suicidal ideation among racially and ethnically diverse college
      students with a history of suicide attempt. From 2012-2013, 1,734 racially and
      ethnically diverse college students completed an on-line survey of suicidal
      behavior and associated factors. Depression, hopelessness, rejection sensitivity,
      and mindfulness, as well as past-year discrimination, ethnic identification, and
      acculturative stress were measured using well-validated self-report instruments.
      The Beck Scale for Suicide Ideation was used to assess current suicidal ideation.
      A subsample of 118 college students who self-reported a past suicide attempt were
      selected for the current analysis. Logistic regression analysis was used to test
      associations between risk factors and the presence of suicidal ideation, and
      linear regression analysis was used to test factors associated with suicidal
      ideation severity among those who reported current suicidal ideation. Depression
      was significantly related to both the presence and severity of current suicidal
      ideation. Mindfulness, and in particular awareness of present moment experience,
      was also inversely associated with ideation severity. We found depression and
      mindlessness were associated with suicidal ideation severity among a sample of
      diverse college students at high risk for suicidal behavior due to a past suicide
      attempt. Factors unique to the minority experience, such as acculturative stress,
      were not associated with current suicidal ideation. Implications for suicide
      prevention are discussed. 

PMID- 26212485
TI  - Vitamin D receptor polymorphisms and growth until adulthood after very premature
      birth.
AB  - The accretion of bone mass is often impaired in preterm infants, which may
      contribute to postnatal growth failure. We tested the effects of the vitamin D
      receptor single-nucleotide polymorphisms (SNPs) c1521g, Fok1, Bsm1, and Taq1 on
      linear growth up until adulthood in 341 subjects born very prematurely (i.e., <32
      weeks of gestation) from the Dutch Project On Preterm and Small-for-gestational
      age infants cohort. The GG genotype of the c1521g SNP was associated with a 0.36
      [95 % confidence interval (CI), 0.02-0.69] SD taller adult stature and the ff
      genotype of the Fok1 SNP with a 0.38 SD (95 % CI, 0.02-0.75) taller adult
      stature. Interaction between these genotypes on stature was observed from the age
      of 1 year onward (albeit nonsignificantly before the age of 5 years), with adult
      height being 1.54 (95 % CI, 0.44-2.63) SD taller in subjects carrying both
      genotypes. The Bsm1 and Taq1 variants were both associated with faster catch-up
      growth until 2 years of age. Statistical correction for potential confounders did
      not change our results. We conclude that homozygosity for the minor alleles of
      both c1521g and Fok1 is associated with a taller adult stature in subjects born
      very prematurely. The minor alleles of Bsm1 and Taq1 are associated with faster
      catch-up growth in infancy. 

PMID- 26212486
TI  - Treatment withdrawal in relapsing-remitting multiple sclerosis: a retrospective
      cohort study.
AB  - BACKGROUND: To investigate the effect of drug withdrawal on the course of
      relapsing-remitting multiple sclerosis (RR-MS). METHODS: An observational cohort
      retrospective study was performed to compare the time to relapse of patients who
      discontinued disease-modifying therapy (1a or 1b beta-interferons or glatiramer
      acetate) with the patients who did not. One hundred and twenty-eight RR-MS
      patients were investigated using a time-dependent approach. RESULTS: Over a
      median follow-up of 108 months, 60 patients discontinued treatment and 89
      relapses were observed. The time to relapse was shorter in patients who
      discontinued treatment compared with those who did not (P < 0.001), median times
      being 31.1 months (95% confidence interval 10.4-50.8) and 85.8 months (95%
      confidence interval 58.6-106.3), respectively, whilst the baseline covariates
      (gender, Expanded Disability Status Scale at diagnosis) did not significantly
      affect the prognosis. CONCLUSIONS: It was found that stopping treatment strongly
      reduces the time to relapse and this information may be useful in patient
      management.

PMID- 26212487
TI  - Relations between causal attributions for stuttering and psychological well-being
      in adults who stutter.
AB  - PURPOSE: This study attempted to understand the relationship between causal
      attributions for stuttering and psychological well-being in adults who stutter.
      METHOD: The study employed a cross-sectional design using a web survey
      distribution mode to gain information related to causal attributions and
      psychological well-being of 348 adults who stutter. Correlation analyses were
      conducted to determine relationships between participants' causal attributions
      (i.e. locus of causality, external control, personal control, stability,
      biological attributions, non-biological attributions) for stuttering and various
      measures of psychological well-being including self-stigma, self-esteem/self
      efficacy, hope, anxiety and depression. RESULT: Results indicated that higher
      perceptions of external control of stuttering were related to significantly lower
      ratings of hope and self-esteem/self-efficacy and higher ratings of anxiety and
      depression. Higher perceptions of personal control of stuttering were related to
      significantly lower ratings of self-stigma and higher ratings of hope and self
      esteem/self-efficacy. Increased biological attributions were significantly
      related to higher ratings of permanency and unchangeableness of stuttering and
      lower ratings of personal control of stuttering. CONCLUSION: The findings
      demonstrate the importance of instilling a sense of control in PWS regarding
      their ability to manage their stuttering. Findings also raise questions regarding
      the benefits of educating PWS about the biological underpinnings of stuttering.

PMID- 26212488
TI  - The categorisation of brands: The case of P&GTM branding strategy.
AB  - In 2 studies, we tested what we considered to be the core of Procter and GambleTM
      (P&GTM) latest branding strategy: making the association between its corporate
      brand and its product brands explicit. Participants were randomly assigned to one
      of the conditions: explicit association between P&GTM and one of its product
      brands and a control condition. Results from Study 1 showed a positive influence
      of the corporate brand on judgements of brand quality for CrestTM. Similarly,
      results from Study 2 showed a positive influence of the corporate brand on
      judgements of brand quality and trust for Oral-BTM. From a multidisciplinary
      perspective, we discussed the theoretical and applied implications of our
      results.

PMID- 26212490
TI  - A randomized controlled trial comparing surgical and non-surgical periodontal
      therapy: a 3-year clinical and cost-effectiveness analysis.
AB  - AIM: To compare immediate surgery to scaling and root planing (SRP) in the
      treatment of advanced periodontitis focusing on the prevalence of residual
      pockets after treatment and cost-effectiveness (1); to elucidate the adjunctive
      effects of azithromycin in a second-treatment phase (2) up to 36 months.
      MATERIALS AND METHODS: Thirty-nine patients (18 males, 21 females; mean age:
      54.6) received oral hygiene instructions and were randomly allocated to surgery
      (n = 19) or SRP (n = 20). Patients with residual pockets (>=6 mm) at 6 months
      received re-debridement of these sites and systemic azithromycin. Clinical
      measurements were performed at 12, 24 and 36 months whereby residual pockets
      underwent re-debridement. Patients were evaluated in terms of clinical response
      parameters and cost-effectiveness. Chair-time was used to assess the financial
      impact of treatment. RESULTS: Only six patients in the surgery group required
      additional treatment at 6 months, whereas 14 patients in the SRP underwent this
      therapy. Both treatment arms were equally effective in terms of clinical outcome
      demonstrating <2% residual pockets at 36 months. Surgery imposed an extra 746
      Euro on the patient up to 6 months compared to SRP. At 36 months, 69 Euro of this
      amount could be offset due to the lower need for re-treatment during maintenance
      phase. CONCLUSIONS: Surgery was ultimately associated with a significantly lower
      need for re-treatment during supportive care, however, at significantly higher
      costs over the 3 years.

PMID- 26212489
TI  - Unique effects on hepatic function, lipid metabolism, bone and growth endocrine
      parameters of estetrol in combined oral contraceptives.
AB  - OBJECTIVES: Estetrol (E4) is a natural estrogen produced by the human fetal
      liver. In combination with drospirenone (DRSP) or levonorgestrel (LNG), E4 blocks
      ovulation and has less effect on haemostatic biomarkers in comparison with
      ethinylestradiol (EE) combined with DRSP. This study evaluates the impact of
      several doses of E4/DRSP and E4/LNG on safety parameters such as liver function,
      lipid metabolism, bone markers and growth endocrine parameters. METHODS: This was
      a dose-finding, single-centre, controlled study performed in healthy women aged
      18 to 35 years with a documented pretreatment ovulatory cycle. Participants
      received 5 mg or 10 mg E4/3 mg DRSP; 5 mg, 10 mg or 20 mg E4/150 MUg LNG; or 20
      MUg EE/3 mg DRSP as a comparator for three consecutive cycles in a 24/4-day
      regimen. Changes from baseline to end of treatment in liver parameters, lipid
      metabolism, bone markers and growth endocrinology were evaluated. RESULTS: A
      total of 109 women were included in the study. Carrier proteins were minimally
      affected in the E4/DRSP and E4/LNG groups, in comparison with the EE/DRSP group,
      where a significant increase in sex hormone-binding globulin was observed.
      Similarly, minor effects on lipoproteins were observed in the E4 groups, and the
      effects on triglycerides elicited by the E4 groups were significantly lower than
      those in the EE/DRSP group. No imbalances in bone markers were observed in any
      groups. No alterations in insulin-like growth factor were observed in the E4
      groups. CONCLUSIONS: E4-containing combinations have a limited effect on liver
      function, lipid metabolism, and bone and growth endocrine parameters.

PMID- 26212491
TI  - Response to: "Coulibaly M, et al. Results of 70 consecutive ulnar nightstick
      fractures" [Injury 2015].

PMID- 26212492
TI  - Possible enhancement of BP180 autoantibody production by herpes zoster.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering disease caused by
      autoantibodies against type XVII collagen/BP180 (BP180). Although the mechanisms
      of autoantibody production remain to be elucidated, herpes virus infections have
      been identified as a possible triggering factor for pemphigus. We report a case
      of herpes zoster (HZ) having anti-BP180 serum antibodies. The patient developed
      sudden-onset, tense blisters and edematous erythema on the right anterior chest,
      shoulder and upper back. Histopathology showed remarkable degeneration of
      keratinocytes, acantholysis and blister formation with ballooning cells,
      indicating herpes virus infection. A polymerase chain reaction analysis of
      varicella zoster virus (VZV) was positive in crusts and effusions from the skin
      lesions, confirming the definitive diagnosis of HZ. Notably, we found that the
      patient had anti-BP180 serum antibodies in association with the occurrence of HZ.
      After successful treatment with valacyclovir hydrochloride for 7 days, the serum
      levels of anti-BP180 antibodies decreased in accordance with the improvement of
      skin lesions. These findings suggest that the production of anti-BP180 antibodies
      could be triggered by the reactivation of VZV. 

PMID- 26212493
TI  - Cognitive and Physical Function by Statin Exposure in Elderly Individuals
      Following Acute Myocardial Infarction.
AB  - Despite beneficial effects on morbidity and mortality after acute myocardial
      infarction (AMI), concerns remain about the safety of statin therapy,
      particularly their potential effects on cognitive and physical function, in
      elderly individuals. Among statin-naive AMI patients age >= 65 years in a
      multicenter US registry, we examined the association between statin prescription
      at discharge and change in cognition (via Modified Telephone Interview for
      Cognitive Status [TICS-M]) assessed at 1 and 6 months after AMI. Short Form-12
      Physical Component score, hand grip, walk time, and chair-rise tests were used to
      assess physical function. We conducted noninferiority testing to evaluate the
      hypothesis that the mean change in cognitive function was no worse among patients
      recently started on statins compared with those who were not. Among 317 elderly
      AMI patients, 262 patients (83%) were prescribed a statin at discharge and 55
      were not. After matching for propensity to be discharged on statin after AMI, the
      effect of statin treatment on change in TICS-M from 1 to 6 months (estimated
      difference, 0.11 points; 95% confidence interval: -2.11 to 2.32, P = 0.92) showed
      noninferiority (inferiority threshold 3 points). There were no significant
      differences in any physical function measure. Among statin-naive elderly
      individuals recovering from AMI, initiation of statin therapy was not associated
      with detectable changes in short-term cognitive or physical function. These
      findings support the general safety of statin therapy for secondary prevention in
      this population.

PMID- 26212495
TI  - Fade to Green: A Biodegradable Stack of Microbial Fuel Cells.
AB  - The focus of this study is the development of biodegradable microbial fuel cells
      (MFCs) able to produce useful power. Reactors with an 8 mL chamber volume were
      designed using all biodegradable products: polylactic acid for the frames,
      natural rubber as the cation-exchange membrane and egg-based, open-to-air
      cathodes coated with a lanolin gas diffusion layer. Forty MFCs were operated in
      various configurations. When fed with urine, the biodegradable stack was able to
      power appliances and was still operational after six months. One useful
      application for this truly sustainable MFC technology includes onboard power
      supplies for biodegradable robotic systems. After operation in remote ecological
      locations, these could degrade harmlessly into the surroundings to leave no trace
      when the mission is complete. 

PMID- 26212494
TI  - The Key Regulator for Language and Speech Development, FOXP2, is a Novel
      Substrate for SUMOylation.
AB  - Transcription factor forkhead box protein P2 (FOXP2) plays an essential role in
      the development of language and speech. However, the transcriptional activity of
      FOXP2 regulated by the post-translational modifications remains unknown. Here, we
      demonstrated that FOXP2 is clearly defined as a SUMO target protein at the
      cellular levels as FOXP2 is covalently modified by both SUMO1 and SUMO3.
      Furthermore, SUMOylation of FOXP2 was significantly decreased by SENP2 (a
      specific SUMOylation protease). We further showed that FOXP2 is selectively
      SUMOylated in vivo on a phylogenetically conserved lysine 674 but the SUMOylation
      does not alter subcellular localization and stability of FOXP2. Interestingly, we
      observed that human etiological FOXP2 R553H mutation robustly reduces its
      SUMOylation potential as compared to wild-type FOXP2. In addition, the acidic
      residues downstream the core SUMO motif on FOXP2 are required for its full
      SUMOylation capacity. Finally, our functional analysis using reporter gene assays
      showed that SUMOylation may modulate transcriptional activity of FOXP2 in
      regulating downstream target genes (DISC1, SRPX2, and MiR200c). Altogether, we
      provide the first evidence that FOXP2 is a substrate for SUMOylation and
      SUMOylation of FOXP2 plays a functional role in regulating its transcriptional
      activity.

PMID- 26212496
TI  - Perfluoroalkyl acids in children and their mothers: Association with drinking
      water and time trends of inner exposures--Results of the Duisburg birth cohort
      and Bochum cohort studies.
AB  - BACKGROUND: Perfluoroalkyl acids (PFAAs) are widely distributed in the
      environment and humans are globally exposed with them. Contaminated drinking
      water can considerably contribute to the inner exposure levels. OBJECTIVES: We
      report the results of a human biomonitoring study with mother-child pairs living
      in two German cities, one city with PFAA contaminated drinking water in the sub
      MUg/l-range (Bochum) and the other one without contamination (Duisburg).
      Furthermore, we studied time trends of exposure levels within the Duisburg cohort
      study. METHODS: We measured seven PFAAs (PFOS, PFOA, PFHxS, PFNA, PFBS, PFDeA,
      PFDoA) in blood samples by high performance liquid chromatography and tandem mass
      spectrometry. Samples were taken during pregnancy, from umbilical cord blood
      (2000-2002), 6-7 years (5th follow-up) and 8-10 years after birth (7th follow
      up). The consumption of drinking water was recorded by a standardized
      questionnaire. Statistical analyses were calculated with multiple linear
      regression models. RESULTS: Children and mothers from Bochum showed higher PFOS
      and PFOA plasma concentrations than from Duisburg. The median concentrations
      (MUg/l) for children were: PFOS 4.7 vs. 3.3; PFOA 6.0 vs. 3.6MUg/l (p<=0.05).
      Consumption of >0.7 l (children) and >0.9 l (mothers) drinking water/day was
      associated with 13-18% higher PFOS, PFOA and PFHxS concentrations in children
      (p<=0.01), and 22% higher PFOA in mothers (p<=0.05). Within the Duisburg cohort,
      PFAA levels in children peaked in the 5th follow-up study (medians (MUg/l): cord
      plasma: 2.7 (PFOS); 1.9 (PFOA); 5th follow-up: 3.6 (PFOS); 4.6 (PFOA); 7th follow
      up: 3.3 (PFOS); 3.6 (PFOA)). PFOS concentrations in mothers declined from
      pregnancy to the 5th follow-up (medians: 8.7 vs. 4.0MUg/l). CONCLUSION: Residents
      exposed to PFOS and PFOA through drinking water showed significantly higher PFOS
      and PFOA concentrations in blood plasma. Although PFAA concentrations in the
      children slightly decreased from the 5th to the 7th follow-up, we detected
      increasing exposure trends with increasing age in the 7th follow-up.

PMID- 26212497
TI  - Coinfection with tuberculosis and paracoccidioidomycosis in French Guiana: a
      common misdiagnosis.

PMID- 26212499
TI  - Transplanted microvascular endothelial cells promote oligodendrocyte precursor
      cell survival in ischemic demyelinating lesions.
AB  - We previously showed that transplantation of brain microvascular endothelial
      cells (MVECs) greatly stimulated remyelination in the white matter infarct of the
      internal capsule (IC) induced by endothelin-1 injection and improved the
      behavioral outcome. In the present study, we examined the effect of MVEC
      transplantation on the infarct volume using intermittent magnetic resonance image
      and on the behavior of oligodendrocyte lineage cells histochemically. Our results
      in vivo show that MVEC transplantation reduced the infarct volume in IC and
      apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate
      that MVECs have a survival effect on OPCs, and this effect might contribute to
      the recovery of the white matter infarct. The conditioned-medium from cultured
      MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from
      cultured fibroblasts did not show such effect. These results suggest a
      possibility that transplanted MVECs increased the number of OPCs through the
      release of humoral factors that prevent their apoptotic death. Identification of
      such humoral factors may lead to the new therapeutic strategy against ischemic
      demyelinating diseases.

PMID- 26212500
TI  - Hierarchical nanostructures of diblock copolymer thin films directed by a saw
      toothed substrate.
AB  - An extensive and systematic calculation was performed to explore hierarchical
      cylindrical structures and the order-to-order transitions of AB diblock
      copolymers (f(A) = 0.3) on a saw-toothed substrate using self-consistent mean
      field theory. We obtained fifteen relatively simple morphologies, including the
      existing morphologies observed experimentally and from simulations, and five more
      complicated structures, by varying the lateral periodicity of the substrate, the
      film thickness of diblock copolymers, the interaction between the A-block and the
      substrate and the tilt angles (or the shape) of the substrate. These structures
      show that the orientation and number of layers of cylinders can be tailored. Even
      lamellae and spherical microdomains were observed. Most interestingly,
      hierarchical structures are also observed, such as the morphology of C(ab)(//)
      within the upper cylinder perpendicular to the bottom cylinder, SC(b)(//)
      morphology that the upper is a cylinder but the bottom is a sphere. In addition,
      we discussed these complex hierarchical structures in detail and have analyzed
      the order-to-order transitions between the cylindrical morphologies with distinct
      orientations and layers.

PMID- 26212498
TI  - miR-218 is essential to establish motor neuron fate as a downstream effector of
      Isl1-Lhx3.
AB  - While microRNAs have emerged as an important component of gene regulatory
      networks, it remains unclear how microRNAs collaborate with transcription factors
      in the gene networks that determines neuronal cell fate. Here we show that in the
      developing spinal cord, the expression of miR-218 is directly upregulated by the
      Isl1-Lhx3 complex, which drives motor neuron fate. Inhibition of miR-218
      suppresses the generation of motor neurons in both chick neural tube and mouse
      embryonic stem cells, suggesting that miR-218 plays a crucial role in motor
      neuron differentiation. Results from unbiased RISC-trap screens, in vivo reporter
      assays and overexpression studies indicated that miR-218 directly represses
      transcripts that promote developmental programs for interneurons. In addition, we
      found that miR-218 activity is required for Isl1-Lhx3 to effectively induce motor
      neurons and suppress interneuron fates. Together our results reveal an essential
      role of miR-218 as a downstream effector of the Isl1-Lhx3 complex in establishing
      motor neuron identity. 

PMID- 26212501
TI  - Ag3PO4 nanoparticles loaded on 3D flower-like spherical MoS2: a highly efficient
      hierarchical heterojunction photocatalyst.
AB  - Novel 3D hierarchical Ag3PO4/MoS2 composites were successfully prepared through a
      facile and reproducible hydrothermal-in situ precipitation method. The 3D flower
      like spherical MoS2 nanoarchitectures acted as an excellent supporting matrix for
      the in situ growth of Ag3PO4 nanoparticles. The photocatalytic performance of the
      composites and the effect of the amount of MoS2 were investigated. The obtained
      hierarchical Ag3PO4/MoS2 composites exhibited significantly enhanced performance
      for photocatalytic oxidation of Rhodamine B (RhB) compared with pure Ag3PO4 under
      visible light irradiation. Ag3PO4/MoS2 composites with 15 wt% of MoS2 showed the
      optimal photoactivity for the degradation of RhB, which was approximately 4.8
      times as high as that of pure Ag3PO4. What's more, the optimal Ag3PO4/MoS2
      composite also showed better photodegradation efficiency for methyl orange (MO)
      and p-chlorophenol (4-CP) than pure Ag3PO4. More attractively, the stability of
      Ag3PO4 was improved after the in situ deposition of Ag3PO4 particles on the
      surface of MoS2 nanoflakes due to the conductivity of MoS2 itself as electron
      acceptors. The enhanced performance of the hierarchical Ag3PO4/MoS2 composites
      under visible light was caused by a synergistic effect including the improved
      separation of photogenerated charge carriers, boosted light harvesting, a
      relatively high surface area and matching energy band structures between the two
      components. Interestingly, the heterostructured Ag3PO4/MoS2 composite reduced the
      use of the noble metal silver, thereby effectively reducing the cost of the
      Ag3PO4 based photocatalyst. Ultimately, a MoS2 involved photocatalytic mechanism
      for the hierarchical Ag3PO4/MoS2 composites was also proposed. 

PMID- 26212502
TI  - Discovery of a Teraryl Oxazolidinone Compound (S)-N-((3-(3-Fluoro-4-(4-(pyridin-2
      yl)-1H-pyrazol-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide Phosphate as a
      Novel Antimicrobial Agent with Enhanced Safety Profile and Efficacies.
AB  - A series of novel teraryl oxazolidinone compounds was designed, synthesized, and
      evaluated for their antimicrobial activity and toxicities. The compounds with
      aromatic N-heterocyclic substituents at the 4-position of pyrazolyl ring showed
      better antibacterial activity against the tested bacteria than other compounds
      with different patterns of substitution. Among all potent compounds, 10f
      exhibited promising safety profile in MTT assays and in hERG K(+) channel
      inhibition test. Furthermore, its phosphate was found to be highly soluble in
      water (47.1 mg/mL), which is beneficial for the subsequent in vivo test. In MRSA
      systemic infection mice models, 10f phosphate exerted significantly improved
      survival protection compared with linezolid. The compound also demonstrated high
      oral bioavailability (F = 99.1%). Moreover, from the results of in vivo
      toxicology experiments, 10f phosphate would be predicted to have less bone marrow
      suppression. 

PMID- 26212503
TI  - Simple Pneumonia or Something More?: A Case Report and Discussion of Unexpected
      Empyema Identified by Point-of-Care Ultrasound.
AB  - There is evidence to suggest that point-of-care ultrasound assessment of the
      lungs has a higher sensitivity and specificity than chest radiography for the
      diagnosis of pneumonia. It is unknown if the same is true for pneumonia
      complications. We present and discuss the case of a 61-year-old woman who
      presented to the emergency department with confusion, decreased level of
      consciousness, and signs of sepsis. A chest x-ray revealed a right sided
      infiltrate. An ultrasound of the patient's lungs was performed, and revealed a
      complex loculated fluid collection consistent with an empyema. A chest CT
      confirmed the diagnosis, and immediate percutaneous drainage was performed. 

PMID- 26212504
TI  - Longitudinal standards for growth velocity of infants from birth to 4 years born
      in West Azerbaijan Province of northwest Iran.
AB  - OBJECTIVES: Growth velocity is an important factor to monitor for appropriate
      child growth. This study presents the growth velocity of infants based on length,
      weight, and head circumference. METHODS: The subjects of this study were 308
      neonates (160 boys and 148 girls) born in West Azerbaijan Province of
      northwestern Iran who were followed from birth for 4 years. The weights and
      lengths of the subjects were recorded at birth, 1, 2, 4, 6, and 9 months, and 1,
      1.5, 2, 3, and 4 years of age, while the head circumferences were measured just
      up to 1.5 years of age. In this study, the Lambda-Mu-Sigma (LMS) method using LMS
      Chartmaker Pro (Institute of Child Health, London, UK) was utilized to obtain
      growth velocity percentiles. RESULTS: After obtaining growth velocity charts for
      weight, length, and head circumference (5th, 50th, and 95th percentiles), the
      researchers could deduce that there was a sharp decrease in the velocity growth
      charts from birth to 2 years of age but these charts remained relatively stable
      up to 4 years for both sexes. Growth velocities for the length and weight of boys
      in the present sample are slightly but not significantly greater than those in
      girls through the first months of infancy and there was no significant difference
      between girls and boys up to 4 years. CONCLUSIONS: This paper provided the first
      local growth velocity standards of length, weight, and head circumference for
      infants by analyzing longitudinal measurements produced for West Azerbaijan
      Province, which should be updated periodically. It seems that there has been a
      significant difference between the growth velocity of infants in northwestern
      Iran and southern Iran within the past few years.

PMID- 26212505
TI  - What predicts the trust of online health information?
AB  - OBJECTIVES: Little attention has been paid to levels of trust in online sources
      of health information. The objective of this study was to investigate levels of
      trust in various sources of health information (interpersonal channels,
      traditional media, and Internet media), and to examine the predictors of trust in
      health information available on the Internet. METHODS: A questionnaire was
      administered to 1,300 people (20 years of age or older), evaluating levels of
      trust in various sources of health information. RESULTS: The highest level of
      trust was expressed regarding interpersonal channels, with hospital physicians
      regarded as the most trusted source of information age and income showed an
      association with trust in online information sources. Elderly people were not
      likely to trust Internet news sources, and high incomes were found to be strongly
      associated with trust in online sources of information overall. CONCLUSIONS:
      Public health organizations must consider the predictors for trust in various
      sources of information in order to employ appropriate media when targeting
      vulnerable individuals or developing messaging strategies for health
      professionals.

PMID- 26212506
TI  - Analysis of survival data in thalassemia patients in Shiraz, Iran.
AB  - OBJECTIVES: The survival rate of thalassemia patients has not been conclusively
      established, and the factors associated with survival remain unclear. This study
      aimed to determine the survival rate of thalassemia among patients in southern
      Iran and to identify the factors associated with mortality from thalassemia.
      METHODS: This retrospective cohort study was conducted based on a retrospective
      review of the medical records of 911 beta-thalassemia patients in 2014. Data
      analysis was conducted using the Kaplan-Meier method and Cox regression analysis.
      RESULTS: Overall, 212 patients (23.3%) died, and 26.8% had thalassemia
      intermedia. The 20-year, 40-year, and 60-year survival rates were 85%, 63%, and
      54%, respectively. Both crude and adjusted analyses found that education, marital
      status, ferritin levels, and comorbidities were related to mortality.
      CONCLUSIONS: Sociodemographic and hematological factors were found to be
      significantly associated with the survival rate of thalassemia. Addressing these
      factors may help healthcare providers and physicians to provide the best possible
      care and to improve the survival rate.

PMID- 26212507
TI  - Demographic characteristics and intravenous drug use among hepatitis C patients
      in the Kota Setar district, Kedah, Malaysia.
AB  - OBJECTIVES: This study explored the demographic characteristics of hepatitis C
      patients in the Kota Setar (KS) district, Kedah, Malaysia, the prevalence of
      intravenous drug use (IVDU) as a risk factor among these patients, and the
      associations between IVDU and demographic characteristics. METHODS: Retrospective
      data pertaining to 713 patients from January 2009 to December 2013 were retrieved
      from hospital and disease notification records for analysis. The risk factors for
      hepatitis C virus (HCV) infection were grouped into IVDU and non-IVDU risk
      factors for analysis using multiple logistic regression. RESULTS: Of the
      hepatitis C patients included in this study, the most common age group was 31 to
      40 years (30.2%), and male patients (91.2%) made up the overwhelming majority.
      Ethnic Malays constituted approximately 80.4% of the patients, and IVDU was the
      main risk factor (77.8%) for HCV infection. Multiple logistic regression showed
      that male patients were 59 times more likely to have IVDU as a risk factor for
      HCV infection. Single patients were 2.5 times more likely to have IVDU as a risk
      factor. Patients aged >=71 years were much less likely than patients aged <=30
      years to have IVDU as a risk factor for HCV infection. CONCLUSIONS: IVDU was
      found to be an important risk factor for HCV infection among patients in the KS
      district. The factors associated with IVDU included age, sex, and marital status.
      Appropriate preventive measures should be developed to target the groups in which
      IVDU is most likely to be a risk factor for HCV infection.

PMID- 26212508
TI  - 2015 MERS outbreak in Korea: hospital-to-hospital transmission.
AB  - The distinct characteristic of the Middle East Respiratory Syndrome (MERS)
      outbreak in South Korea is that it not only involves intra-hospital transmission,
      but it also involves hospital-to-hospital transmission. It has been the largest
      MERS outbreak outside the Middle East, with 186 confirmed cases and, among them,
      36 fatal cases as of July 26, 2015. All confirmed cases are suspected to be
      hospital-acquired infections except one case of household transmission and two
      cases still undergoing examination. The Korean health care system has been the
      major factor shaping the unique characteristics of the outbreak. Taking this as
      an opportunity, the Korean government should carefully assess the fundamental
      problems of the vulnerability to hospital infection and make short- as well as
      long-term plans for countermeasures. In addition, it is hoped that this journal,
      Epidemiology and Health, becomes a place where various topics regarding MERS can
      be discussed and shared. 

PMID- 26212509
TI  - [Conductive hearing loss caused by ear canal stenosis].

PMID- 26212510
TI  - Bugging bugs.

PMID- 26212511
TI  - Impact of Atrial Fibrillation Duration on the Success of First-Time Concomitant
      Cox Maze Procedures.
AB  - BACKGROUND: Atrial fibrillation (AF) duration is one of the most consistent
      predictors of Cox maze (CM) procedure failure. We examined the impact of AF
      duration on CM success in patients having first-time concomitant surgery.
      METHODS: First-time concomitant CM was performed in 505 patients. Freedom from
      atrial arrhythmia (AA) and class I/III antiarrhythmic drug (AAD) data were
      collected prospectively. Patients with longer AF duration (>= 5 years; n = 113)
      were compared with shorter duration (<5 years; n = 392) in primary analyses. The
      AF duration was examined as a continuous variable in regression analyses.
      RESULTS: Patients with longer AF duration were older (68.4 vs 65.1 years, p =
      0.002) and in long-standing persistent AF (80% vs 36%, p < 0.001). Freedom from
      AA and AA off AAD was lower in longer duration patients at 1 year (80% vs 94%, p
      < 0.001; 74 vs 87%, p = 0.005) and 2 years (69 vs 90%, p < 0.001; 61 vs 81%, p =
      0.001). Freedom from stroke or transient ischemic attack (TIA) was similar (96.1%
      vs 95.4%, p = 0.65). Adjusting for clinical and AF-associated factors, each 1
      year increase in AF duration had 13% greater odds for failure at 1 year (odds
      ratio [OR], 1.13, p = 0.004) and 20% greater odds at 2 years (OR, 1.20, p <
      0.001). Cryothermia as sole energy source attenuated the negative impact of AF
      duration on 1-year success. CONCLUSIONS: Longer AF duration significantly
      impacted CM success and may result from extensive tissue remodeling. Patients
      with longer AF duration can expect reasonable success rates, especially when on
      AAD, and low stroke rates during follow-up. Cryoablation may reduce AF duration
      impact on success compared with combined bipolar radiofrequency and cryothermia.

PMID- 26212512
TI  - Distal Transverse Arch to Left Carotid Artery Ratio Helps to Identify Infants
      With Aortic Arch Hypoplasia.
AB  - BACKGROUND: Aortic coarctation (CoA) with concomitant aortic arch hypoplasia
      (AAH) is associated with an increased risk of hypertension after surgical repair.
      The differentiation of CoA with or without AAH may be critical to delineate the
      ideal surgical approach that best ameliorates postoperative hypertension. Since
      2000, we have defined CoA with AAH when the diameter of the distal transverse
      aortic arch is equal to or less than the diameter of the left carotid artery. We
      hypothesized that, based on our definition, aortic tissue from infants having CoA
      with AAH would demonstrate distinct genetic expression patterns as compared with
      infants having CoA alone. METHODS: From 6 infants (AAH, 3; CoA, 3), an Affymetrix
      1.0 genome array identified genes in the coarctation/arch region that were
      differentially expressed between infants having CoA with AAH versus CoA alone.
      Reverse transcription polymerase chain reaction validated genetic differences
      from a cohort of 21 infants (CoA with AAH, 10; CoA, 11). To evaluate the clinical
      outcomes based on our definition of CoA with AAH, we reviewed infants repaired
      using this algorithm from 2000 to 2010. RESULTS: Microarray data demonstrated
      genes differentially expressed between groups. Reverse transcription polymerase
      chain reaction confirmed that CoA with AAH was associated with an increased
      expression of genes involved in cardiac and vascular development and growth,
      including hepsin, fibroblast growth factor-18, and T-box 2. The clinical outcomes
      of 79 infants (AAH, 26; CoA, 53) demonstrated that 90.1% were free of
      hypertension at 13 years when managed with this surgical strategy. CONCLUSIONS:
      These findings provide evidence that the ratio of the diameter of the distal
      transverse arch to the left carotid artery may be helpful to identify CoA with
      AAH and, when used to delineate the surgical approach, may minimize hypertension.

PMID- 26212513
TI  - Small Single-Incision Thoracoscopic Surgery Using an Anchoring Suture in Patients
      With Primary Spontaneous Pneumothorax: A Safe and Feasible Procedure.
AB  - BACKGROUND: Single-incision thoracoscopic surgery is an alternative procedure
      used to treat primary spontaneous pneumothorax, although conventional three- or
      four-port video-assisted thoracoscopic surgery is the recognized standard
      procedure. Single-incision thoracoscopic surgery is not yet popular when a wedge
      resection is required during general thoracic surgery, including pneumothorax
      surgery and lung biopsy, because of the danger of collision between instruments
      during surgery. In addition, introducing all of the instruments through a single
      incision means that a relatively large incision is required, leading to less than
      satisfactory cosmetic outcomes. The purpose of this study was to show that our in
      house surgical method is a safe, alternative procedure for treating a primary
      spontaneous pneumothorax. METHODS: A total of 104 patients underwent our in-house
      surgical procedure to treat primary spontaneous pneumothorax from October 2012 to
      October 2014. Mean patient age was 22.7 +/- 8.8 years; 91 patients were male and
      13 were female. We used a wound protector intraoperatively, and placed an
      anchoring suture at the point of the bleb lesion, permitting us to retract the
      lung, which enabled us to create a small skin incision (<2 cm). We only inserted
      a stapler and the scope through this small incision when we performed the wedge
      resection; no lung manipulation (normally requiring instrumentation) was
      necessary. A total of 107 surgeries were performed (3 patients experienced
      contralateral recurrences). All clinical data were analyzed retrospectively.
      RESULTS: Mean operative time (107 surgeries) was 49.7 +/- 13.9 minutes, and the
      mean duration of thoracic catheter insertion was 4.1 +/- 1.0 days. Three cases
      were converted to two- or three-port video-assisted thoracoscopic surgery during
      the operation. Three patients experienced prolonged air leakage (>5 days). No
      other complication was recorded. The Wong-Baker pain scores on postoperative days
      0, 1, and 2 were 2.4 +/- 1.0, 2.3 +/- 1.3, and 1.7 +/- 0.83, respectively. The
      mean duration of postoperative hospital stay was 4.8 +/- 1.7 days. The mean
      follow-up period was 11 +/- 6 months. Twelve patients experienced chest wall
      paresthesia (11.2%). One ipsilateral pneumothorax recurrence was encountered
      during follow-up. CONCLUSIONS: Small (<2 cm) single-incision thoracoscopic
      surgery using a wound protector and a bidirectional anchoring suture was safe and
      feasible and yielded acceptable outcomes for treating primary spontaneous
      pneumothorax.

PMID- 26212514
TI  - Comparison of Hemodynamics After Aortic Root Replacement Using Valve-Sparing or
      Bioprosthetic Valved Conduit.
AB  - BACKGROUND: The purpose of this study is to compare aortic hemodynamics and blood
      flow patterns using in-vivo four-dimensional (4D) flow magnetic resonance imaging
      (MRI) in patients after valve-sparing aortic root replacement (VSARR) and aortic
      root replacement with bioprosthetic valves (BIO-ARR). METHODS: In-vivo 4D flow
      MRI was performed in 11 patients after VSARR (47 +/- 18 years, 6 bicuspid aortic
      valves, 5 trileaflet aortic valves), 16 patients after BIO-ARR (52 +/- 14 years),
      and 10 healthy controls (47 +/- 16 years). Analysis included three-dimensional
      blood flow visualization and grading of helix flow in the ascending aorta (AAo)
      and arch. Peak systolic velocity was quantified in 9 analysis planes in the AAo,
      aortic arch, and descending aorta. Flow profile uniformity was evaluated in the
      aortic root and ascending aorta. RESULTS: Peak systolic velocity (2.0 to
      2.5m/second) in the aortic root and AAo in both VSARR and BIO-ARR were elevated
      compared with controls (1.1 to 1.3m/second, p < 0.005). Flow asymmetry in BIO-ARR
      was increased compared with VSARR, evidenced by more AAo outflow jets (9 of 16
      BIO-ARR, 0 of 11 in VSARR). The BIO-ARR exhibited significantly (p < 0.001)
      increased helix flow in the AAo as a measure of increased flow derangement.
      Finally, peak systolic velocities were elevated at the aortic root for BIO-ARR
      (2.5 vs 2.0m/second, p < 0.05) but lower in the distal AAo when compared with
      VSARR. CONCLUSIONS: The VSARR results in improved hemodynamic outcomes when
      compared with BIO-ARR, as indicated by reduced peak velocities in the aortic root
      and less helix flow in the AAo by 4D flow MRI. Longitudinal research assessing
      the clinical impact of these differences in hemodynamic outcomes is warranted.

PMID- 26212515
TI  - Current trends in stenting for aortic coarctation in Japan: Subanalysis of
      Japanese Society of Pediatric Interventional Cardiology (JPIC) stent survey.
AB  - BACKGROUND: Stenting for aortic coarctation (CoA) has been accepted as an
      alternative to surgery for adolescents and adults, but only a few case have been
      reported in Japan. The purpose of this study was to provide a detailed review of
      Japanese national data on stenting of CoA. METHODS: In a subanalysis of the data
      of the Japanese Society of Pediatric Interventional Cardiology (JPIC), we
      identified 35 patients with CoA who underwent stenting. We analyzed procedural
      characteristics including factors that may have contributed to hemodynamic
      effectiveness, and we compared these parameters between the patients under and
      over 15 years of age. RESULTS: The mean ratio of balloon diameter/minimum lumen
      diameter (MLD) before stenting was 1.7 (range, 1.2-4.0), and the mean difference
      between the balloon diameter and the reference vessel diameter was -0.7 mm
      (range, -5.0 to +3.0 mm). %MLD/balloon diameter, which was defined as [(balloon
      diameter - MLD after dilation)/balloon diameter] * 100 predicted achievement of
      <10 mmHg pressure gradient after stenting. The sensitivity and the specificity of
      its cut-off of 7% were 93% and 47% (AUC, 0.7), respectively. There was no
      statistical difference between the two age groups under and over 15 years of age,
      in terms of selection criteria of stent size, balloon type used for deployment
      and immediate angiographic and hemodynamic result. CONCLUSIONS: Stenting for CoA
      was clinically effective with few complications in Japan, even in patients not
      fully grown.

PMID- 26212516
TI  - Achievement of complete remission predicts outcome of allogeneic haematopoietic
      stem cell transplantation in patients with chronic myelomonocytic leukaemia. A
      study of the Chronic Malignancies Working Party of the European Group for Blood
      and Marrow Transplantation.
AB  - The results of allogeneic stem cell transplantation (allo-SCT) in chronic
      myelomonocytic leukaemia (CMML) are usually reported together with other
      categories of myelodysplastic syndrome. We analysed transplantation outcome in
      513 patients with CMML, with a median age of 53 years reported to the European
      Group for Blood and Marrow Transplantation. Conditioning was standard (n = 249)
      or reduced-intensity (n = 226). Donors were human leucocyte antigen-related (n =
      285) or unrelated (n = 228). Disease status at transplantation was complete
      remission (CR) in 122 patients, no CR in 344, and unknown in 47. Engraftment was
      successful in 95%. Grades 2-4 acute graft-versus-host disease (GvHD) occurred in
      33% of the patients and chronic GvHD was reported in 24%. The 4-year cumulative
      incidence of non-relapse mortality was 41% and 32% for relapse, resulting in a 4
      year estimated relapse-free and overall survival (OS) of 27% and 33%,
      respectively. Patients transplanted in CR had lower probability for non-relapse
      death (P = 0.002) and longer relapse-free and OS (P = 0.001 and P = 0.005,
      respectively). In multivariate analysis the only significant prognostic factor
      for survival was the presence of CR at transplantation (P = 0.005). Allo-SCT
      remains a curative treatment option for patients with CMML and should preferably
      be performed early after diagnosis or after establishing the best possible
      remission status.

PMID- 26212517
TI  - Comparison of conventional versus Hybrid knife peroral endoscopic myotomy methods
      for esophageal achalasia: a case-control study.
AB  - OBJECTIVE: Peroral endoscopic myotomy (POEM) has been developed to treat
      achalasia as a novel less invasive modality. We aimed to compare the efficacy and
      safety of conventional knife versus Hybrid knife (HK) during POEM procedure.
      MATERIALS AND METHODS: Between June 2012 and July 2014, 31 patients underwent
      POEM using HK in our department (HK group), and 36 patients underwent POEM using
      conventional method (injection needle and triangular tip [TT] knife, TT group).
      Procedure-related parameters, symptom relief, adverse events were compared
      between two groups. RESULTS: There were no significant differences in the age,
      sex and other baseline characteristics between the two groups. The mean
      procedural time was significantly shorter in HK group than TT group (53.0 +/-
      17.2 vs. 67.6 +/- 28.4 min, p = 0.015). The mean frequency of devices exchange
      was 4.7 +/- 1.7 in HK group and 10.9 +/- 1.8 in TT group (p = 0.000). No serious
      adverse events occurred postoperatively in both groups. At one-year follow-up, a
      total of 94% treatment success was achieved in all patients (93.5% in HK group
      and 94.4% in TT group, p = 0.877). CONCLUSION: HK in POEM can shorten the
      procedural time, and achieve similar treatment success compared to conventional
      TT knife.

PMID- 26212519
TI  - Changes in the Swine Gut Microbiota in Response to Porcine Epidemic Diarrhea
      Infection.
AB  - The gastrointestinal tract of mammals is a complex ecosystem with distinct
      environments and comprises hundreds of different types of bacterial cells. The
      gut microbiota may play a critical role in the gut health of the host. We herein
      attempted to identify a microbiota shift that may be affected by porcine epidemic
      diarrhea (PED). We observed significant differences in microbiota between the
      control and PED virus (PEDV)-infected groups at both the phylum and genus level.
      Most commensal bacteria (i.e. Psychrobacter, Prevotella, and Faecalibacterium) in
      the healthy gastrointestinal tract were decreased due to dysbiosis induced by
      PEDV infection. 

PMID- 26212518
TI  - Effects of Hemagglutination Activity in the Serum of a Deep-Sea Vent Endemic
      Crab, Shinkaia Crosnieri, on Non-Symbiotic and Symbiotic Bacteria.
AB  - In deep-sea hydrothermal environments, most invertebrates associate with dense
      populations of symbiotic microorganisms in order to obtain nutrition. The
      molecular interactions between deep-sea animals and environmental microbes,
      including their symbionts, have not yet been elucidated in detail.
      Hemagglutinins/lectins, which are carbohydrate-binding proteins, have recently
      been reported to play important roles in a wide array of biological processes,
      including the recognition and control of non-self materials. We herein assessed
      hemagglutination activity in the serum of a deep-sea vent endemic crab, Shinkaia
      crosnieri, which harbors chemosynthetic epibionts on its plumose setae. Horse and
      rabbit erythrocytes were agglutinated using this serum (opt. pH 7.5 and opt.
      temperature 15 degrees C). Agglutinating activity was inhibited by eight kinds of
      sugars and several divalent cations, did not require any divalent metal ions, and
      remained detectable even after heating the serum at 100 degrees C for 30 min. By
      using fluorescently labeled serum, we demonstrated that deep-sea crab serum
      components bound to the epibionts even in the presence of sugars. This study
      represents the first immunological assessment of a deep-sea vent endemic crab and
      demonstrated the possibility of a non-lectin-mediated symbiont-host interaction. 

PMID- 26212520
TI  - Bayes factor and posterior probability: Complementary statistical evidence to p
      value.
AB  - As a convention, a p-value is often computed in hypothesis testing and compared
      with the nominal level of 0.05 to determine whether to reject the null
      hypothesis. Although the smaller the p-value, the more significant the
      statistical test, it is difficult to perceive the p-value in a probability scale
      and quantify it as the strength of the data against the null hypothesis. In
      contrast, the Bayesian posterior probability of the null hypothesis has an
      explicit interpretation of how strong the data support the null. We make a
      comparison of the p-value and the posterior probability by considering a recent
      clinical trial. The results show that even when we reject the null hypothesis,
      there is still a substantial probability (around 20%) that the null is true. Not
      only should we examine whether the data would have rarely occurred under the null
      hypothesis, but we also need to know whether the data would be rare under the
      alternative. As a result, the p-value only provides one side of the information,
      for which the Bayes factor and posterior probability may offer complementary
      evidence.

PMID- 26212521
TI  - A novel highly sensitive and specific flow cytometry system for cervical cancer
      screening.
AB  - PURPOSE: This study assessed the performance of a novel flow cytometry (FCM)
      cervical cancer screening system compared with human papillomavirus (HPV) Hybrid
      Capture 2 (HC2). METHODS: Chinese women aged 20years or older were enrolled in
      this study at Fudan University Shanghai Cancer Center. All participants underwent
      cytology/pathology testing (gold standard), HPV HC2 testing and FCM testing
      involving analysis of cell proliferation index (CPIx). RESULTS: Among 437 women
      enrolled in this study, 185 women (42.3%) were diagnosed as "gold standard
      positive" by pathology with diseases including cervical intraepithelial neoplasia
      (CIN) grade 2 (n=11), CIN3 (n=41), squamous cell carcinoma (SCC; n=115),
      adenocarcinoma in situ (n=2) and adenocarcinoma (n=16). The remaining 252 cases
      were deemed "gold standard negative". The sensitivity was 87.6% (95% CI, 82.8
      92.3) for FCM testing and 89.7% (95% CI, 85.4-94.1; p=0.5121) for HPV HC2
      testing. The specificity of FCM testing was 90.5% (95% CI, 86.2-94.7), which was
      superior to the specificity of HPV HC2 testing (84.5%, 95% CI, 79.3-89.7;
      p=0.04). In the 20-29years old group, the sensitivity and the specificity of FCM
      testing were 90.0% (95% CI, 71.4-100.0) and 92.9% (95% CI, 76.9-100.0),
      respectively. The FCM testing CPIx statistically increased with the transition
      from normal cervical specimens to SCC specimens. CONCLUSIONS: Our results showed
      that the FCM screening system had high sensitivity and specificity for women of
      various ages. The FCM CPIx was able to evaluate the severity of disease
      quantitatively.

PMID- 26212522
TI  - Understanding Americans' views on opioid pain reliever abuse.
AB  - AIMS: Opioid pain reliever abuse rates have increased sharply in the United
      States. This study examines Americans' personal experience with opioid pain
      reliever use and abuse, and views about the seriousness of the problem, factors
      causing it, responsibility for addressing it and support for policies to resolve
      it. DESIGN: Public opinion survey. SETTING AND PARTICIPANTS: A nationally
      representative US adult sample (n = 1111). MEASURES: Experiences with opioid pain
      relievers and views about the seriousness, causes of and responsibility for
      addressing the problem, and support for policies to reduce opioid pain reliever
      abuse. FINDINGS: 28.2 per cent of Americans reported using opioid pain relievers
      in the last 12 months, 69.5% have used them in their life-time and 17.3% reported
      using these medications when not prescribed to them. Fifty-eight per cent ranked
      the problem as serious, on a par with other major health concerns. Individual
      orientated factors, including a lack of understanding about how easy it is to
      become addicted (80.0%) and improper storage (65.1%) and disposal (64.1%), ranked
      highest as causes, and those abusing opioid pain relievers (83.8%) and their
      physicians (78.0%) were viewed as most responsible for solving the problem. Of
      the policies recommended to curb the epidemic, 14 of 16 were supported by a
      majority of Americans. CONCLUSIONS: Americans view the problem of opioid pain
      reliever abuse as serious, and support nearly all the policies recommended by
      medical, law enforcement, disease control and public health experts to curb the
      epidemic.

PMID- 26212523
TI  - Effects of pterostilbene and resveratrol on brain and behavior.
AB  - Age is the greatest universal risk factor for neurodegenerative diseases. During
      aging, these conditions progress from minor loss of function to major disruptions
      in daily life, loss of independence and ultimately death. Because approximately
      25% of the world population is expected to be older than age 65 by 2050, and no
      treatments exist to halt or reverse ongoing neurodegeneration, the need for
      effective prevention strategies is more pressing that ever before. A growing body
      of research supports the role of diet in healthy aging, particularly diets rich
      in bioactive phytochemical compounds. Recently, stilbenes such as resveratrol (3,
      5, 4'-trans-trihydroxystilbene) and its analogue, pterostilbene, have gained a
      significant amount of attention for their potent antioxidant, anti-inflammatory,
      and anticarcinogenic properties. However, evidence for the beneficial effects of
      stilbenes on cerebral function is just beginning to emerge. In this review, we
      summarize the current knowledge on the role of resveratrol and pterostilbene in
      improving brain health during aging, with specific focus on antioxidant and anti
      inflammatory signaling and behavioral outcomes. 

PMID- 26212524
TI  - Association Between Serum Uric Acid Levels/Hyperuricemia and Hypertension Among
      85,286 Japanese Workers.
AB  - This cross-sectional study from January 2012 to December 2012 aimed to examine
      the sex-specific association between serum uric acid (SUA) levels/hyperuricemia
      and hypertension among Japanese patients. SUA level, medical histories, and
      lifestyle-related items were collected from 85,286 of 136,770 participants. Among
      those with hyperuricemia, the median age was 46 years and 97% were men, which was
      significantly different than those without hyperurecemia (44 years and 56%,
      respectively; P<.01). Hyperuricemia was 1.79 times more likely in hypertensive
      men than normotensive men and almost six times more likely in hypertensive women
      (odds ratio=5.92 and adjusted odds ratio=1.33 for men and adjusted odds
      ratio=1.81 for women) after multivariate analysis. SUA quartiles positively
      correlated with systolic and diastolic blood pressures in both sexes.
      Hyperuricemia and SUA levels were significantly associated with hypertension in
      both sexes. These findings underscore the importance of maintaining normal SUA
      levels to manage and prevent hypertension. Better management of SUA as well as
      blood pressure may have potential in preventing future cardiovascular disorders.

PMID- 26212525
TI  - Dysphagia and Aspiration.

PMID- 26212526
TI  - The GVK EMRI maternal and neonatal transport system in India: a mega plan for a
      mammoth problem.
AB  - Maternal and infant mortality has been a major concern in India with the
      Government taking serious efforts to achieve the Millennium Development Goals by
      2015. Ganapathy Venkata Krishna Reddy Emergency Management and Research Institute
      (GVK EMRI) is one such effort and is the country's first emergency service
      provider working under the public-private partnership model to provide emergency
      response services and quality pre-hospital care to any sick person, pregnant
      mothers, and sick neonates. Since the introduction of the emergency medical
      services, institutional deliveries have increased in all states and union
      territories where the ambulances have been deployed and the majority of mothers
      have been provided the required emergency care at the appropriate time. This in
      turn has helped in considerably reducing the maternal mortality. GVK EMRI has
      partnered with the government of Tamil Nadu and deployed specialized neonatal
      ambulances to ensure safe transport of newborns. The safe transport of sick,
      vulnerable neonates and the improvement in survival of transported neonates over
      the years advocate scaling up of this program to other states, which would
      greatly contribute towards reducing infant and neonatal mortality. 

PMID- 26212527
TI  - Evaluation of anti-acne properties of phloretin in vitro and in vivo.
AB  - OBJECTIVE: This study aimed to investigate the anti-acne properties of phloretin
      in vitro and in vivo. METHODS: Anti-microbial activity against Propionibacterium
      acnes (P. acnes), Propionibacterium granulosum (P. granulosum) and Staphylococcus
      epidermidis (S. epidermidis) were observed by the minimum inhibitory
      concentration (MIC) and disc diffusion methods. The anti-inflammatory effects
      were studied in HaCaT cells based on P. acnes-induced inflammatory mediators,
      including PGE2 and COX-2, examined through enzyme-linked immunosorbent assay
      (ELISA) and luciferase reporter gene assay. Thirty healthy subjects with
      whiteheads participated in the clinical study. Comedo counting, and the amount of
      sebum and porphyrin were measured before treatment and following 4 consecutive
      weeks of treatment with phloretin. RESULTS: Phloretin showed anti-microbial
      activities against P. acnes, P. granulosum, S. epidermidis with the MIC of 0.5,
      0.5 and 0.25 mg mL(-1) , respectively. P. acnes-induced activation of the COX-2
      promoter was markedly attenuated by phloretin treatment. Consistent with these
      results, inhibition of PGE2 production was also observed. In 1-month, placebo
      controlled trials, phloretin showed clinically and statistically significant
      reduction of comedo counts and sebum output level. Compared to before treatment,
      whiteheads, blackheads, papules, sebum output level and amount of sebum and
      porphyrin were significantly decreased at 4 weeks in the test group. CONCLUSIONS:
      This study revealed that phloretin inhibits the growth of P. acnes, P.
      granulosum, and S. epidermidis. In addition, we demonstrated that phloretin
      attenuates COX-2 and PGE2 expression during the P. acnes-induced upregulation of
      inflammatory signalling. Clinical studies further suggested that treatment with
      formulations containing phloretin confers anti-acne benefits. Based on these
      results, we suggest that phloretin may be introduced as a possible acne
      mitigating agent.

PMID- 26212528
TI  - Durability and tolerability of dapagliflozin over 52 weeks as add-on to metformin
      and sulphonylurea in type 2 diabetes.
AB  - AIMS: To evaluate the safety and efficacy of dapagliflozin as add-on therapy to
      metformin plus sulphonylurea over 52 weeks. METHODS: Patients with type 2
      diabetes mellitus (T2DM) using sulphonylurea and metformin received dapagliflozin
      10 mg/day or placebo added to therapy for 52 weeks (24-week randomized, double
      blind period plus 28-week double-blind extension). RESULTS: A total of 219
      patients were randomized 1 : 1 to dapagliflozin or placebo. Over 52 weeks,
      glycated haemoglobin (HbA1c) and fasting plasma glucose levels showed greater
      improvement from baseline with dapagliflozin (-0.8% and -1.5 mmol/l) than with
      placebo (-0.1% and 0.6 mmol/l). More patients achieved HbA1c <7.0% with
      dapagliflozin (27.3%) than with placebo (11.3%) at 52 weeks. Dapagliflozin was
      associated with greater reductions in body weight and systolic blood pressure (
      2.9 kg and -1.0 mmHg) compared with placebo (-1.0 kg and 1.1 mmHg). Greater
      increases in total, LDL and HDL cholesterol and decreases in triglycerides were
      observed with dapagliflozin (3.4, 4.8, 6.9 and -8.0%, respectively) versus
      placebo (1.4, 0.9, 0.6 and 2.9%, respectively). Fewer patients were rescued for
      failing to reach glycaemic targets with dapagliflozin (9.3%) than with placebo
      (44.4%). Adverse events and serious adverse events were similar between groups
      (dapagliflozin: 69.7 and 6.4%; placebo: 73.4 and 7.3%). More hypoglycaemic events
      were observed with dapagliflozin (15.6%) than with placebo (8.3%). Genital
      infections were reported in more patients in the dapagliflozin (10.1%) than in
      the placebo group (0.9%) and urinary tract infection frequency was similar in the
      two groups (10.1 and 11.0%). CONCLUSION: Dapagliflozin as add-on to metformin
      plus a sulphonylurea was well tolerated and improvement in glycaemic control was
      maintained over 52 weeks.

PMID- 26212530
TI  - ?

PMID- 26212529
TI  - A novel laminin beta gene BmLanB1-w regulates wing-specific cell adhesion in
      silkworm, Bombyx mori.
AB  - Laminins are important basement membrane (BM) components with crucial roles in
      development. The numbers of laminin isoforms in various organisms are determined
      by the composition of the different alpha, beta, and gamma chains, and their
      coding genes, which are variable across spieces. In insects, only two alpha, one
      beta, and one gamma chains have been identified thus far. Here, we isolated a
      novel laminin beta gene, BmLanB1-w, by positional cloning of the mutant
      (crayfish, cf) with blistered wings in silkworm. Gene structure analysis showed
      that a 2 bp deletion of the BmLanB1-w gene in the cf mutant caused a frame-shift
      in the open reading frame (ORF) and generated a premature stop codon. Knockdown
      of the BmLanB1-w gene produced individuals exhibiting blistered wings, indicating
      that this laminin gene was required for cell adhesion during wing development. We
      also identified laminin homologs in different species and showed that two copies
      of beta laminin likely originated in Lepidoptera during evolution. Furthermore,
      phylogenetic and gene expression analyses of silkworm laminin genes revealed that
      the BmLanB1-w gene is newly evolved, and is required for wing-specific cell
      adhesion. This is the first report showing the tissue specific distribution and
      functional differentiation of beta laminin in insects. 

PMID- 26212531
TI  - ?

PMID- 26212532
TI  - ?

PMID- 26212533
TI  - ?

PMID- 26212534
TI  - ?

PMID- 26212535
TI  - ?

PMID- 26212536
TI  - ?

PMID- 26212537
TI  - ?

PMID- 26212538
TI  - ?

PMID- 26212539
TI  - ?

PMID- 26212540
TI  - A novel synthetic compound exerts effective anti-tumour activity in vivo via the
      inhibition of tubulin polymerisation in A549 cells.
AB  - Microtubules are critical elements that are involved in a wide range of cellular
      processes, and thus, they have become an attractive target for many anticancer
      drugs. A novel synthesised compound, 12P, was identified as new microtubule
      inhibitor. This compound inhibits tubulin polymerisation through binding to the
      colchicine-binding site of tubulin. 12P exhibits excellent anti-proliferative
      activities against a panel of human cancer cell lines, with IC50 values range
      from 9 to 55nM. Interestingly, compound 12P also displayed equally potent
      cytotoxicity against several drug-resistant cell lines, and it showed high
      selectivity for active human umbilical vein endothelial cells (HUVECs). Further
      flow cytometric analysis showed that 12P induces G2/M phase arrest and apoptosis
      in A549 cells. Cellular studies have revealed that the induction of apoptosis by
      12P was associated with a collapse of mitochondrial membrane potential (MMP),
      accumulation of reactive oxygen species (ROS), alterations in the expression of
      some cell cycle-related proteins (e.g. Cyclin B1, Cdc25c, Cdc2) and some
      apoptosis-related proteins (e.g. Bax, Bad, Bcl-2, Bcl-xl). Importantly, 12P
      significantly reduced the growth of xenograft tumours of A549 cells in vivo
      (tumour inhibitory rate of 12P: 84.2%), without any loss of body weight. Taken
      together, these in vitro and in vivo results suggested that 12P may become a
      promising lead compound for the development of new anticancer drugs.

PMID- 26212542
TI  - T-cell receptors modify neuronal function in the central nervous system.
AB  - Recent published findings have shown that many proteins discovered in the immune
      system and residing on immune cells with well established immune-related
      functions are also found in neurons of the central nervous system. These studies
      have uncovered a rich variety of neuronal functions attributed to these immune
      proteins. This review will focus on two key interacting protein complexes that
      previously were known for adaptive immune reactions, the major histocompatability
      complex and the T-cell receptor complex. We will review where these immune
      proteins are expressed in the CNS and their neuronal function. 

PMID- 26212541
TI  - The effect of alpha7 nicotinic receptor activation on glutamatergic transmission
      in the hippocampus.
AB  - Nicotinic acetylcholine receptors (nAChRs) are expressed widely in the CNS, and
      mediate both synaptic and perisynaptic activities of endogenous cholinergic
      inputs and pharmacological actions of exogenous compounds (e.g., nicotine and
      choline). Behavioral studies indicate that nicotine improves such cognitive
      functions as learning and memory, however the cellular mechanism of these actions
      remains elusive. With help from newly developed biosensors and optogenetic tools,
      recent studies provide new insights on signaling mechanisms involved in the
      activation of nAChRs. Here we will review alpha7 nAChR's action in the tri
      synaptic pathway in the hippocampus. The effects of alpha7 nAChR activation via
      either exogenous compounds or endogenous cholinergic innervation are detailed for
      spontaneous and evoked glutamatergic synaptic transmission and synaptic
      plasticity, as well as the underlying signaling mechanisms. In summary, alpha7
      nAChRs trigger intracellular calcium rise and calcium-dependent signaling
      pathways to enhance glutamate release and induce glutamatergic synaptic
      plasticity. 

PMID- 26212543
TI  - Metabolomics reveals the formation of aldehydes and iminium in gefitinib
      metabolism.
AB  - Gefitinib (GEF), an inhibitor of epidermal growth factor receptor (EGFR) tyrosine
      kinase, is widely used for the treatment of cancers, particularly non-small cell
      lung cancer. However, its clinical use is limited by multiple adverse effects
      associated with GEF, such as liver and lung injuries, severe nausea, and
      diarrhea. Although, the exact mechanism of GEF adverse effects are still unknown,
      xenobiotic-induced bioactivation is thought to play a significant role in GEF
      induced toxicity. Using a metabolomic approach, we investigated the metabolic
      pathways of GEF in human and mouse liver microsomes. Thirty four GEF metabolites
      and adducts were identified and half of them are novel. The potential reactive
      metabolites, two aldehydes and one iminium, were identified for the first time.
      The previously reported GSH adducts and primary amines were observed as well. The
      aldehyde and iminium pathways were further confirmed by using methoxylamine and
      potassium cyanide as trapping reagents. Using recombinant CYP450 isoforms, CYP3A4
      inhibitor, and S9 from Cyp3a-null mice, we confirmed CYP3A is the major enzyme
      contributing to the formation of aldehydes, GSH adducts, and primary amines in
      liver. Multiple enzymes contribute to the formation of iminium. This study
      provided us more knowledge of GEF bioactivation and enzymes involved in metabolic
      pathways, which can be utilized for understanding the mechanism of adverse
      effects associated with GEF and predicting possible drug-drug interactions.
      Further studies are suggested to determine the roles of these bioactivation
      pathways in GEF toxicity. 

PMID- 26212544
TI  - A new pharmacological effect of levornidazole: Inhibition of NLRP3 inflammasome
      activation.
AB  - Levornidazole, which was originally used to inhibit anaerobic and protozoal
      infections, is currently known to possess a novel pharmacological effect. In this
      study, we investigated the possible modulation by levornidazole of NOD-like
      receptor protein 3 (NLRP3) inflammasome-mediated IL-1beta and IL-18 release from
      macrophages. The NLRP3 inflammasome could be activated by lipopolysaccharide
      (LPS) plus ATP or monosodium urate (MSU) in PMA-pretreated THP-1 macrophages.
      Surprisingly, an in vitro study showed that levornidazole suppressed IL-1beta and
      IL-18 secretion by blocking the activation of the NLRP3 inflammasome. However,
      dextrornidazole barely suppressed the NLRP3 inflammasome. Levornidazole displays
      activity similar to that of dextrornidazole against clinical anaerobic bacteria,
      and they possess the same pharmacokinetic properties. Moreover, both of these
      compounds were unable to ameliorate T cell-mediated inflammation. Therefore, we
      used the widely applied NLRP3 inflammasome-related models of dextran sodium
      sulfate (DSS)-induced colitis and LPS-induced endotoxin shock to confirm the
      novel pharmacological effect of levornidazole in vivo. The in vivo studies
      verified the novel activity of levornidazole because the inhibition of NLRP3
      inflammasome by levornidazole contributed to a better ameliorating effect than
      that of dextrornidazole in the in vivo models tested. Furthermore, this
      inhibitory effect of levornidazole was found to be at least partially achieved by
      decreasing the mitochondrial ROS generation without inhibiting NF-kappaB
      activation. In summary, these data describe a new pharmacological effect of
      levornidazole as an inhibitor of NLRP3 inflammasome activation. 

PMID- 26212545
TI  - Sugiol inhibits STAT3 activity via regulation of transketolase and ROS-mediated
      ERK activation in DU145 prostate carcinoma cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) is constitutively
      activated in various human cancers and has been used as a therapeutic target for
      tumors. This study screened natural products to identify compounds that inhibit
      STAT3 activity using a STAT3-dependent luciferase reporter system. Sugiol was
      identified as a compound that decreased luciferase activity in a dose-dependent
      manner. Sugiol specifically inhibited STAT3 phosphorylation at Tyr-705 in DU145
      prostate cells, and this inhibition was independent of the STAT3 upstream kinase.
      Sugiol induced cell cycle arrest and decreased the expression levels of STAT3
      target genes, such as cyclin D1, cyclin A, and survivin. Notably, we observed
      that sugiol interacted with transketolase, an enzyme in central metabolism, and
      increased ROS levels leading to the activation of ERK, which inhibits STAT3
      activity. The protein phosphatase MEG2 was also responsible for sugiol-induced
      STAT3 dephosphorylation. The inhibitory effect of sugiol on cell growth was
      confirmed using the DU145 mouse xenograft model. We propose that sugiol inhibits
      STAT3 activity through a mechanism that involves the inhibition of transketolase,
      which leads to increased ROS levels and MEG2 activation in DU145 cells.
      Therefore, sugiol is the first compound regulating STAT3 activity via modulation
      of cancer metabolic pathway and we suggest the use of sugiol as an inhibitor of
      the STAT3 pathway for the treatment of human solid tumors with activated STAT3. 

PMID- 26212546
TI  - The answer is not 42.
AB  - During his long and illustrious career that now spans over 50 years David Triggle
      has had a major impact on biomedical science that can be linked to his research
      spanning the disciplines of chemistry and biology. Capitalizing on his
      undergraduate and postgraduate education in chemistry David's early research
      explored the pharmacology of adreno- and muscarinic receptors ultimately leading
      to studies of the cellular signaling processes that mediated the effects of
      receptor activation particularly with respect to calcium homeostasis. David's
      contributions to the identification and development of calcium channel
      antagonists resulted in benefits beyond the impact of such drugs in the treatment
      of diseases of the cardiovascular system. During David's 50+ year career many
      technological changes have occurred that have affected how research is conducted,
      funded and published and how its impact evaluated. Not all of these technological
      advances are necessarily positive and it is valuable to reflect on the long
      lasting impact of David's accomplishments with reference to such changes. 

PMID- 26212547
TI  - Pharmacological induction of mitochondrial biogenesis as a therapeutic strategy
      for the treatment of type 2 diabetes.
AB  - Defects in mitochondrial oxidative function have been associated with the onset
      of type 2 diabetes. Although the causal relationship between mitochondrial
      dysfunction and diabetes has not been fully established, numerous studies
      indicate that improved glucose homeostasis achieved via lifestyle interventions,
      such as exercise or calorie restriction, is tightly associated with increased
      mitochondrial biogenesis and oxidative function. Therefore, it is conceivable
      that potentiating mitochondrial biogenesis by pharmacological means could
      constitute an efficacious therapeutic strategy that would particularly benefit
      those diabetic patients who cannot adhere to comprehensive programs based on
      changes in lifestyle or that require a relatively rapid improvement in their
      diabetic status. In this review, we discuss several pharmacological targets and
      drugs that modulate mitochondrial biogenesis as well as their potential use as
      treatments for insulin resistance and diabetes. 

PMID- 26212548
TI  - Metabolic mapping of A3 adenosine receptor agonist MRS5980.
AB  - (1S,2R,3S,4R,5S)-4-(2-((5-Chlorothiophen-2-yl)ethynyl)-6-(methylamino)-9H-purin-9
      yl)-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide (MRS5980) is an A3AR
      selective agonist containing multiple receptor affinity- and selectivity
      enhancing modifications and a therapeutic candidate drug for many inflammatory
      diseases. Metabolism-related poor pharmacokinetic behavior and toxicities are a
      major reason for drug R&D failure. Metabolomics with UPLC-MS was employed to
      profile the metabolism of MRS5980 and MRS5980-induced disruption of endogenous
      compounds. Recombinant drug-metabolizing enzymes screening experiment were used
      to determine the enzymes involved in MRS5980 metabolism. Analysis of lipid
      metabolism-related genes was performed to investigate the reason for MRS5980
      induced lipid metabolic disorders. Unsupervised principal components analysis
      separated the control and MRS5980 treatment groups in feces, urine, and liver
      samples, but not in bile and serum. The major ions mainly contributing to the
      separation of feces and urine were oxidized MRS5980, glutathione (GSH) conjugates
      and cysteine conjugate (degradation product of the GSH conjugates) of MRS5980.
      The major ions contributing to the group separation of liver samples were
      phosphatidylcholines. In vitro incubation experiments showed the involvement of
      CYP3A enzymes in the oxidative metabolism of MRS5980 and direct GSH reactivity of
      MRS5980. The electrophilic attack by MRS5980 is a minor pathway and did not alter
      GSH levels in liver or liver histology, and thus may be of minor clinical
      consequence. Gene expression analysis further showed decreased expression of PC
      biosynthetic genes choline kinase a and b, which further accelerated conversion
      of lysophosphatidylcholine to phosphatidylcholines through increasing the
      expression of lysophosphatidylcholine acyltransferase 3. These data will be
      useful to guide rational design of drugs targeting A3AR, considering efficacy,
      metabolic elimination, and electrophilic reactivity. 

PMID- 26212550
TI  - Minocycline enhances mitomycin C-induced cytotoxicity through down-regulating
      ERK1/2-mediated Rad51 expression in human non-small cell lung cancer cells.
AB  - Minocycline is a semisynthetic tetracycline derivative; it has anti-inflammatory
      and anti-cancer effects distinct from its antimicrobial function. However, the
      molecular mechanism of minocycline-induced cytotoxicity in non-small cell lung
      cancer (NSCLC) cells has not been identified. Rad51 plays a central role in
      homologous recombination and high levels of Rad51 expression are observed in
      chemo- or radioresistant carcinomas. Our previous studies have shown that the
      MKK1/2-ERK1/2 signal pathway maintains the expression of Rad51 in NSCLC cells. In
      this study, minocycline treatment inhibited cell viability and proliferation of
      two NSCLC cells, A549 and H1975. Treatment with minocycline decreased Rad51 mRNA
      and protein levels through MKK1/2-ERK1/2 inactivation. Furthermore, expression of
      constitutively active MKK1 (MKK1-CA) vectors significantly rescued the decreased
      Rad51 protein and mRNA levels in minocycline-treated NSCLC cells. However,
      combined treatment with MKK1/2 inhibitor U0126 and minocycline further decreased
      the Rad51 expression and cell viability of NSCLC cells. Knocking down Rad51
      expression by transfection with small interfering RNA of Rad51 enhanced the
      cytotoxicity and cell growth inhibition of minocycline. Mitomycin C (MMC) is
      typically used as a first or second line regimen to treat NSCLC. Compared to a
      single agent alone, MMC combined with minocycline resulted in cytotoxicity and
      cell growth inhibition synergistically in NSCLC cells, accompanied with reduced
      activation of phospho-ERK1/2, and reduced Rad51 protein levels. Overexpression of
      MKK1-CA or Flag-tagged Rad51 could reverse the minocycline and MMC-induced
      synergistic cytotoxicity. These findings may have implications for the rational
      design of future drug regimens incorporating minocycline and MMC for the
      treatment of NSCLC. 

PMID- 26212549
TI  - Altered energy state reversibly controls smooth muscle contractile function in
      human saphenous vein during acute hypoxia-reoxygenation: Role of glycogen, AMP
      activated protein kinase, and insulin-independent glucose uptake.
AB  - Hypoxia is known to promote vasodilation of coronary vessels through several
      mediators including cardiac-derived adenosine and endothelium-derived prostanoids
      and nitric oxide. To date, the impact of endogenous glycogen depletion in
      vascular smooth muscle and the resultant alterations in cellular energy state
      (e.g., AMP-activated protein kinase, AMPK) on the contractile response to G
      protein-coupled receptor agonists (e.g., serotonin, 5-HT) has not yet been
      studied. In the present study, ex vivo exposure of endothelium-denuded human
      saphenous vein rings to hypoxic and glucose-deprived conditions during KCl
      induced contractions for 30 min resulted in a marked depletion of endogenous
      glycogen by ~80% (from ~1.78 MUmol/g under normoxia to ~0.36 MUmol/g under
      hypoxia). Importantly, glycogen-depleted HSV rings, which were maintained under
      hypoxia/reoxygenation and glucose-deprived conditions, exhibited significant
      increases in basal AMPK phosphorylation (~6-fold ?) and 5-HT-induced AMPK
      phosphorylation (~19-fold ?) with an accompanying suppression of 5-HT-induced
      maximal contractile response (~68% ?), compared with respective controls.
      Exposure of glycogen-depleted HSV rings to exogenous D-glucose, but not the
      inactive glucose analogs, prevented the exaggerated increase in 5-HT-induced AMPK
      phosphorylation and restored 5-HT-induced maximal contractile response. In
      addition, the ability of exogenous D-glucose to rescue cellular stress and
      impaired contractile function occurred through GLUT1-mediated but insulin/GLUT4
      independent mechanisms. Together, the present findings from clinically-relevant
      human saphenous vein suggest that the loss of endogenous glycogen in vascular
      smooth muscle and the resultant accentuation of AMPK phosphorylation by GPCR
      agonists may constitute a yet another mechanism of metabolic vasodilation of
      coronary vessels in ischemic heart disease.

PMID- 26212552
TI  - David J. Triggle: A personal and retrospective overview of an academic journey.
AB  - My association with David Triggle began when I was a post-doctoral associate in
      his laboratory during the 1960s. Our relationship continued for decades as
      faculty colleagues and presently, when our formal academic links have ceased,
      memories of our friendship and shared experiences remain strong and fresh. What
      follows are some glimpses of the scientist, educator and an intellectually
      versatile individual that I have been privileged to know. 

PMID- 26212551
TI  - Alpha7 nicotinic receptor activation protects against oxidative stress via heme
      oxygenase I induction.
AB  - Subchronic oxidative stress and inflammation are being increasingly implicated in
      the pathogenesis of numerous diseases, such as Alzheimer's or Parkinson's
      disease. This study was designed to evaluate the potential protective role of
      alpha7 nicotinic receptor activation in an in vitro model of neurodegeneration
      based on subchronic oxidative stress. Rat organotypic hippocampal cultures (OHCs)
      were exposed for 4 days to low concentration of lipopolysaccharide (LPS) and the
      complex III mitochondrial blocker, antimycin-A. Antimycin-A (0.1MUM) and
      lipopolysaccharide (1ng/ml) caused low neurotoxicity on their own, measured as
      propidium iodide fluorescence in CA1 and CA3 regions. However, their combination
      (LPS/AA) caused a greater detrimental effect, in addition to mitochondrial
      depolarization, overproduction of reactive oxygen species (ROS) and Nox4
      overexpression. Antimycin-A per se increased ROS and mitochondrial
      depolarization, although these effects were significantly higher when combined
      with LPS. More interesting was the finding that exposure of OHCs to the
      combination of LPS/AA triggered aberrant protein aggregation, measured as
      thioflavin S immunofluorescence. The alpha7 nicotinic receptor agonist,
      PNU282987, prevented the neurotoxicity and the pathological hallmarks observed in
      the LPS/AA subchronic toxicity model (oxidative stress and protein aggregates);
      these effects were blocked by alpha-bungarotoxin and tin protoporphyrin,
      indicating the participation of alpha7 nAChRs and heme-oxygenase I induction. In
      conclusion, subchronic exposure of OHCs to low concentration of antimycin-A plus
      LPS reproduced pathological features of neurodegenerative disorders. alpha7 nAChR
      activation ameliorated these alterations by a mechanism involving heme-oxygenase
      I induction. 

PMID- 26212553
TI  - Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice.
AB  - Withaferin-A (WA) has anti-oxidant activities however, its therapeutic potential
      in acetaminophen (APAP) hepatotoxicity is unknown. We performed a proof-of
      concept study to assess the therapeutic potential of WA in a mouse model that
      mimics APAP-induced liver injury (AILI) in humans. Overnight fasted C57BL/6NTac
      (5-6 wk. old) male mice received 200 mg/kg APAP intraperitoneally (i.p.). After 1
      h mice were treated with 40 mg/kg WA or vehicle i.p., and euthanized 4 and 16 h
      later; their livers were harvested and serum collected for analysis. At 4 h,
      compared to vehicle-treated mice, WA-treated mice had reduced serum ALT levels,
      hepatocyte necrosis and intrahepatic hemorrhage. All APAP-treated mice had
      reduced hepatic glutathione (GSH) levels however, reduction in GSH was lower in
      WA-treated when compared to vehicle-treated mice. Compared to vehicle-treated
      mice, livers from WA-treated mice had reduced APAP-induced JNK activation,
      mitochondrial Bax translocation, and nitrotyrosine generation. Compared to
      vehicle-treated mice, WA-treated mice had increased hepatic up-regulation of
      Nrf2, Gclc and Nqo1, and down-regulation of Il-6 and Il-1beta. The
      hepatoprotective effect of WA persisted at 16 h. Compared to vehicle-treated
      mice, WA-treated mice had reduced hepatocyte necrosis and hepatic expression of
      Il-6, Tnf-alpha and Il-1beta, increased hepatic Gclc and Nqo1 expression and GSH
      levels, and reduced lipid peroxidation. Finally, in AML12 hepatocytes, WA reduced
      H2O2-induced oxidative stress and necrosis by preventing GSH depletion.
      Collectively, these data show mechanisms whereby WA reduces necrotic hepatocyte
      injury, and demonstrate that WA has therapeutic potential in AILI.

PMID- 26212555
TI  - Development of a diffuse reflectance infrared Fourier transform spectroscopy
      (DRIFTS) cell for the in situ analysis of co-electrolysis in a solid oxide cell.
AB  - Co-electrolysis of carbon dioxide and steam has been shown to be an efficient way
      to produce syngas, however further optimisation requires detailed understanding
      of the complex reactions, transport processes and degradation mechanisms
      occurring in the solid oxide cell (SOC) during operation. Whilst electrochemical
      measurements are currently conducted in situ, many analytical techniques can only
      be used ex situ and may even be destructive to the cell (e.g. SEM imaging of the
      microstructure). In order to fully understand and characterise co-electrolysis,
      in situ monitoring of the reactants, products and SOC is necessary. Diffuse
      Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) is ideal for in situ
      monitoring of co-electrolysis as both gaseous and adsorbed CO and CO2 species can
      be detected, however it has previously not been used for this purpose. The
      challenges of designing an experimental rig which allows optical access alongside
      electrochemical measurements at high temperature and operates in a dual
      atmosphere are discussed. The rig developed has thus far been used for symmetric
      cell testing at temperatures from 450  degrees C to 600  degrees C. Under a CO
      atmosphere, significant changes in spectra were observed even over a simple
      Au|10Sc1CeSZ|Au SOC. The changes relate to a combination of CO oxidation, the
      water gas shift reaction, carbonate formation and decomposition processes, with
      the dominant process being both potential and temperature dependent. 

PMID- 26212554
TI  - Modulation of aggressive behavior in mice by nicotinic receptor subtypes.
AB  - Aggression is frequently comorbid with neuropsychiatric conditions and is a
      predictor of worse outcomes, yet current pharmacotherapies are insufficient and
      have debilitating side effects, precluding broad use. Multiple models of
      aggression across species suggest that the nicotinic acetylcholine receptor
      (nAChR) agonist nicotine has anti-aggressive (serenic) properties. Here we
      demonstrate dose-dependent serenic effects of acute nicotine administration in
      three distinct mouse strains: C57BL/6, BALB/c, and CD1. While acute nicotine
      administration (0.25mg/kg) modestly reduced solitary homecage locomotion, this
      could not account for nicotine's serenic effects since social encounters
      eliminated the hypolocomotor effect, and nicotine did not alter social
      interaction times. Pretreatment with the homomeric (alpha7 subunit) nAChR
      antagonist methyllycaconitine (5mg/kg), but not the heteromeric (beta2 or beta4
      subunit-containing) nAChR antagonist dihydro-beta-erythroidine (DHbetaE, 3mg/kg),
      blocked the serenic effects of nicotine. By contrast, pretreatment with DHbetaE
      blocked the effect of acute nicotine administration on locomotion, uncoupling
      nicotine's serenic and hypolocomotor effects. Finally, the alpha7 nAChR partial
      agonist GTS-21 reduced aggression in C57BL/6 mice. These results support the idea
      that acute nicotine administration has serenic effects and provide evidence for
      specificity of this effect distinct from effects on locomotion. Furthermore,
      pharmacological studies suggest that activation of alpha7 nAChRs underlies the
      serenic effects of nicotine. Further studies of nAChRs could enhance
      understanding of the neurobiology of aggression and may lead to the development
      of novel, more specific treatments for pathological aggression. 

PMID- 26212556
TI  - Patient Radiation Dose Reduction during Transarterial Chemoembolization Using a
      Novel X-Ray Imaging Platform.
AB  - PURPOSE: To evaluate radiation dose reduction in patients undergoing
      transarterial chemoembolization with the use of a new image acquisition and
      processing platform. MATERIALS AND METHODS: Radiation-dose data were obtained
      from 176 consecutive chemoembolization procedures in 135 patients performed in a
      single angiography suite. From January 2013 through October 2013, 85 procedures
      were performed by using our institution's standard fluoroscopic settings. After
      upgrading the x-ray fluoroscopy system with an image acquisition and processing
      platform designed to reduce image noise and reduce skin entrance dose, 91
      chemoembolization procedures were performed from November 2013 through December
      2014. Cumulative dose-area product (CDAP), cumulative air kerma (CAK), and total
      fluoroscopy time were recorded for each procedure. Image quality was assessed by
      three interventional radiologists blinded to the x-ray acquisition platform used.
      RESULTS: Patient radiation dose indicators were significantly lower for
      chemoembolization procedures performed with the novel imaging platform. Mean CDAP
      decreased from 3,033.2 dGy.cm(2) (range, 600.3-9,404.1 dGy.cm(2)) to 1,640.1
      dGy.cm(2) (range, 278.6-6,779.9 dGy.cm(2); 45.9% reduction; P < .00001). Mean CAK
      decreased from 1,445.4 mGy (range, 303.6-5,233.7 mGy) to 971.7 mGy (range, 144.2
      3,512.0 mGy; 32.8% reduction; P < .0001). A 20.3% increase in mean total
      fluoroscopy time was noted after upgrading the imaging platform, but blinded
      analysis of the image quality revealed no significant degradation. CONCLUSIONS:
      Although a small increase in fluoroscopy time was observed, a significant
      reduction in patient radiation dose was achieved by using the optimized imaging
      platform, without image quality degradation.

PMID- 26212557
TI  - Achievable dose reduction using iterative reconstruction for chest computed
      tomography: A systematic review.
AB  - OBJECTIVES: Iterative reconstruction (IR) allows for dose reduction with
      maintained image quality in CT imaging. In this systematic review the reported
      effective dose reductions for chest CT and the effects on image quality are
      investigated. METHODS: A systematic search in PubMed and EMBASE was performed.
      Primary outcome was the reported local reference and reduced effective dose and
      secondary outcome was the image quality with IR. Both non contrast-enhanced and
      enhanced studies comparing reference dose with reduced dose were included.
      RESULTS: 24 studies were included. The median number of patients per study was 66
      (range 23-200) with in total 1806 patients. The median reported local reference
      dose of contrast-enhanced chest CT with FBP was 2.6 (range 1.5-21.8) mSv. This
      decreased to 1.4 (range 0.4-7.3) mSv at reduced dose levels using IR. With non
      contrast-enhanced chest CT the dose decreased from 3.4 (range 0.7-7.8) mSv to 0.9
      (range 0.1-4.5) mSv. Objective mage quality and diagnostic confidence and
      acceptability remained the same or improved with IR compared to FBP in most
      studies while data on diagnostic accuracy was limited. CONCLUSION: Radiation dose
      can be reduced to less than 2 mSv for contrast-enhanced chest CT and non contrast
      enhanced chest CT is possible at a submillisievert dose using IR algorithms.

PMID- 26212558
TI  - Unilateral enlargement of the mandible in a child.

PMID- 26212559
TI  - Identification of acute myocardial infarction in patients with atrial
      fibrillation and chest pain with a contemporary sensitive troponin I assay.
AB  - BACKGROUND: The introduction of modern troponin assays has facilitated diagnosis
      of acute myocardial infarction due to improved sensitivity with corresponding
      loss of specificity. Atrial fibrillation (AF) is associated with elevated levels
      of troponin. The aim of the present study was to evaluate the diagnostic
      performance of troponin I in patients with suspected acute coronary syndrome and
      chronic AF. METHODS: Contemporary sensitive troponin I was assayed in a
      derivation cohort of 90 patients with suspected acute coronary syndrome and
      chronic AF to establish diagnostic cut-offs. These thresholds were validated in
      an independent cohort of 314 patients with suspected myocardial infarction and AF
      upon presentation. Additionally, changes in troponin I concentration within 3
      hours were used. RESULTS: In the derivation cohort, optimized thresholds with
      respect to a rule-out strategy with high sensitivity and a rule-in strategy with
      high specificity were established. In the validation cohort, application of the
      rule-out cut-off led to a negative predictive value of 97 %. The rule-in cut-off
      was associated with a positive predictive value of 88 % compared with 71 % if
      using the 99th percentile cut-off. In patients with troponin I levels above the
      specificity-optimized threshold, additional use of the 3-hour change in
      absolute/relative concentration resulted in a further improved positive
      predictive value of 96 %/100 %. CONCLUSIONS: Troponin I concentration and the 3
      hour change in its concentration provide valid diagnostic information in patients
      with suspected myocardial infarction and chronic AF. With regard to AF-associated
      elevation of troponin levels, application of diagnostic cut-offs other than the
      99th percentile might be beneficial.

PMID- 26212561
TI  - Investigation on Single-walled Carbon Nanotubes-Liposomes Conjugate to Treatment
      Tumor with Dual-mechanism.
AB  - Single-walled carbon nanotubes (SWNT) have been widely explored as carriers for
      drug delivery because of their large surface area, high near-infrared absorption
      coefficient and facile transport through cellular membranes. In this study,
      Lysine (Lys) modified SWNT-liposomes conjugate loaded with doxorubicin (DOX) was
      designed to enhance the targeted drug delivery and antitumor effect. The
      conjugate (DOX-Lys/SWNT-Lip) was prepared with pH gradient methods, and the mean
      particle size and drug entrapment efficiency were 223+/-5.9 nm and 85.9 %,
      respectively. In vitro drug release study showed that DOX released much slowly
      from DOX-Lys/SWNT-Lip than from DOX solution, but faster than that of DOX
      Lys/SWNT. DOX-Lys/SWNT-Lip could efficiently cross the cell membrane and afford
      higher anti-tumor efficacy on MCF-7 cells in vitro. For in vivo experiment,
      normal saline (N.S.), and DOX or DOX-Lys/SWNTLip were given to the S180 tumor
      bearing mice by i.v. administration, and followed by exposing the tumor site to
      nearinfrared laser (NIR) irradiation at 808 nm for 2 min. The relative tumor
      volumes in DOX-Lys/SWNT-Lip group and DOX group were obviously smaller than those
      of N.S. group. When combined with NIR laser irradiation, the suppression on tumor
      growth was much stronger. In conclusion, this study may provide potentially
      viable clinical strategies for tumor treatment with chemotherapy and photothermal
      therapy dual-mechanism.

PMID- 26212562
TI  - Comparative Pharmacokinetics, Tissue Distribution, Excretion of Recombinant
      LiverTargeting Interferon with IFN alpha2b Administered Intramuscular in Rats.
AB  - Interferon alpha2b (IFN alpha2b) is the first cytokine, which has been approved
      by FDA to treat chronic hepatitis B. However, it has no organ or tissue
      selectivity effect, and will be rapidly cleared out in the liver after the
      administration treatment. In our previous study, a novel liver-targeting fusion
      interferon (IFN-CSP) was constructed by recombining human IFN alpha2b with a CSP
      region I-plus peptide. The purpose of this study is to compare pharmacokinetics,
      tissue distribution, excretion of recombinant liver-targeting interferon IFN-CSP
      with IFN alpha2b following intramuscular administration in rats and estimate
      whether the fusion protein recombinant liver-targeting interferon has liver
      targeting effect. Serum, tissue, urinary, fecal, and biliary concentrations of
      the drug were measured at various time points after administration using ELISA
      test. The pharmacokinetic character of IFN-CSP and IFNalpha2b was described using
      a non-compartmental model after a single intramuscular administration. Our
      results showed that there were no significant differences between these two drugs
      in pharmacokinetic and elimination. However, drug concentration of recombinant
      liver-targeting IFN was higher than IFN alpha2b in the liver after intramuscular
      administration in rats at different time points. It was increased in the spleen
      but not apparently, and decreased in the heart, lung and kidney. In conclusion,
      compared with traditional IFN ?2b, the novel recombinant liver-targeting IFN will
      be more accumulated in the liver tissue. With this excellent property, IFN-CSP
      shows a great application prospect in clinical treatment, although further
      investigation is still needed.

PMID- 26212560
TI  - Automated chest-radiography as a triage for Xpert testing in resource-constrained
      settings: a prospective study of diagnostic accuracy and costs.
AB  - Molecular tests hold great potential for tuberculosis (TB) diagnosis, but are
      costly, time consuming, and HIV-infected patients are often sputum scarce.
      Therefore, alternative approaches are needed. We evaluated automated digital
      chest radiography (ACR) as a rapid and cheap pre-screen test prior to Xpert
      MTB/RIF (Xpert). 388 suspected TB subjects underwent chest radiography, Xpert and
      sputum culture testing. Radiographs were analysed by computer software (CAD4TB)
      and specialist readers, and abnormality scores were allocated. A triage algorithm
      was simulated in which subjects with a score above a threshold underwent Xpert.
      We computed sensitivity, specificity, cost per screened subject (CSS), cost per
      notified TB case (CNTBC) and throughput for different diagnostic thresholds.
      18.3% of subjects had culture positive TB. For Xpert alone, sensitivity was
      78.9%, specificity 98.1%, CSS $13.09 and CNTBC $90.70. In a pre-screening setting
      where 40% of subjects would undergo Xpert, CSS decreased to $6.72 and CNTBC to
      $54.34, with eight TB cases missed and throughput increased from 45 to 113
      patients/day. Specialists, on average, read 57% of radiographs as abnormal,
      reducing CSS ($8.95) and CNTBC ($64.84). ACR pre-screening could substantially
      reduce costs, and increase daily throughput with few TB cases missed. These data
      inform public health policy in resource-constrained settings. 

PMID- 26212563
TI  - Opportunities for Nano-Formulations in Type 2 Diabetes Mellitus Treatments.
AB  - Diabetes mellitus has been a threat to humans for many years. Amongst the
      different diabetes types, type 2 diabetes mellitus is the most common, and this
      is due to drastic changes in human lifestyle such as lack of exercise, stressful
      life and so on. There are a large number of conventional treatment methods
      available for type 2 diabetes mellitus. However, most of these methods are
      curative and are only applicable when the patient is highly symptomatic.
      Effective treatment strategies should be geared towards interfering with cellular
      and bio molecular mechanisms associated with the development and sustenance of
      the disease. In recent years, research into the medical potential of
      nanoparticles has been a major endeavor within the pharmaceutical industries.
      Nanoparticles display unique and tuneable biophysical characteristics which are
      determined by their shape and size. Nanoparticles have been used to manifest the
      properties of drugs, and as carriers for drug and vaccine delivery.
      Notwithstanding, there are further opportunities for nanoparticles to augment the
      treatment of a wide range of life threatening diseases that are yet to be
      explored. This review article seeks to highlight the application of potential
      nano-formulations in the treatment of type 2 diabetes mellitus. In addition, the
      activity of nanomedicine supplements in reversing insulin resistance is also
      discussed.

PMID- 26212564
TI  - Remodeling Tumor Vasculature to Enhance Delivery of Intermediate-Sized
      Nanoparticles.
AB  - Restoration of dysfunctional tumor vasculature can reestablish the pressure
      gradient between intravascular and interstitial space that is essential for
      transporting nanomedicines into solid tumors. Morphologic and functional
      normalization of tumor vessels improves tissue perfusion to facilitate
      intratumoral nanoparticle delivery. However, this remodeling process also reduces
      tumor vessel permeability, which can impair nanoparticle transport. Although
      nanoparticles sized below 10 nm maximally benefited from tumor vessel
      normalization therapy for enhanced nanomedicine delivery, the small particle size
      severely limits its applicability. Here, we show that intermediate-sized
      nanoparticles (20-40 nm) can also benefit from tumor vasculature remodeling. We
      demonstrate that a window of opportunity exists for a two-stage transport
      strategy of different nanoparticle sizes. Overall, tumor vessel remodeling
      enhances the transvascular delivery of intermediate-size nanoparticles of up to
      40 nm. Once within the tumor matrix, however, smaller nanoparticles experience a
      significantly lesser degree of diffusional hindrance, resulting in a more
      homogeneous distribution within the tumor interstitium. These findings suggest
      that antiangiogenic therapy and nanoparticle design can be combined in a
      multistage fashion, with two sets of size-inclusion criteria, to achieve optimal
      nanomedicine delivery into solid tumors. 

PMID- 26212567
TI  - Pd-catalytic hydrodechlorination of chlorinated hydrocarbons in groundwater using
      H2 produced by a dual-anode system.
AB  - Water electrolysis has been employed for in situ supplying H2 to Pd-catalytic
      treatment of groundwater, but the treatment efficiency is greatly inhibited by
      the concomitant production of O2. In this study, a new dual-anode system is
      proposed to improve the efficiency. An inert anode and an iron anode are used
      simultaneously to produce O2 and Fe(II), respectively. The quick oxidative
      precipitation of Fe(II) by O2 removes both Fe(II) and O2, improving the
      utilization of cathodic H2 for the subsequent Pd-catalytic hydrodechlorination.
      Feasibility tests in the lab show that Pd-catalytic hydrodechlorination of
      trichloroethylene (TCE) was considerably increased by the addition of an iron
      anode to the conventional two-electrode system. Scale-up tests at an abandoned
      chemical site demonstrated that chlorobenzenes in the groundwater were largely
      hydrodechlorinated to benzene, showing a maximum efficiency with the currents of
      0.24 and 0.16 A applied to the inert and iron anodes, respectively, at the flow
      rate of 6 L/h. In a 3-month intermittent field test, Pd normalized rate constants
      of hydrodechlorinating three chlorobenzenes are comparable to the conventional
      means of H2 supply, while the cost for hydrodechlorination normalized by one mole
      [H] is much lower. The dual-anode system is an effective means to supplying H2 in
      situ for Pd-catalytic treatment.

PMID- 26212568
TI  - Simultaneous analysis of Alternaria toxins and citrinin in tomato: an optimised
      method using liquid chromatography-tandem mass spectrometry.
AB  - Alternaria toxins and citrinin are mycotoxins produced by fungi growing on
      different raw materials and agricultural commodities. Maximum levels of these
      toxins in foods are currently under consideration by the European Commission as a
      risk management measure. In this study, a new quantitative method is described
      for the determination of five Alternaria toxins and citrinin in tomato and tomato
      juice samples based on LC-MS/MS detection. Samples were extracted with pure
      methanol, followed by a derivatisation step with 2,4-dinitrophenylhydrazine to
      improve the determination of tenuazonic acid and to decrease the wide polarity
      difference between the compounds of interest. Samples were purified on
      hydrophilic-modified styrene polymer solid-phase extraction cartridges. High
      performance liquid chromatographic columns packed with different core-shell
      materials were tested for the separation of toxins and a C-18 phase was in the
      final method applied to achieve sufficient separation of all relevant analytes. A
      key element of this approach was to prove successful transferability of the
      method to three different triple quadrupole mass spectrometers. A full single
      laboratory method validation was performed on two LC-MS/MS systems and
      performance characteristics met the predefined requirements. Moreover, the method
      was used in an international proficiency test and the satisfactory z-scores
      obtained (-0.1 to 0.8 in tomato juice samples) demonstrated the reliability of
      the approach described. The method will be validated in an inter-laboratory
      collaborative study and if the criteria for method precision are met, the method
      will be proposed as a new Work Item to the European Committee for
      Standardisation. 

PMID- 26212569
TI  - Assessment of Outpatient and Inpatient Antibiotic Treatment Patterns and Health
      Care Costs of Patients with Complicated Urinary Tract Infections.
AB  - PURPOSE: The goal of this study was to examine treatment patterns, utilization,
      and costs for complicated urinary tract infections (UTIs) requiring
      inpatient/emergency department (ED) and outpatient care. METHODS: This
      observational study evaluated inpatient/ED-treated and outpatient-treated
      patients (aged >=18 years) with complicated UTIs from 2 large US administrative
      claims databases (HealthCore Integrated Research Environment and Premier
      Perspective Database). Patient identification depended on treatment setting:
      outpatients had 2 UTI diagnosis-related office visits and 2 claims for different
      antibiotics within 30 days, and inpatients had a UTI-related hospitalization/ED
      visit after 1 UTI diagnosis-related office visit plus 2 claims for different
      antibiotics within 30 days. The index date for outpatients was the date of the
      first office visit; for inpatients, it was the date of admission/ED visit. Both
      cohorts had continuous insurance eligibility. Outcomes were assessed by using
      univariate and multivariate statistics. FINDINGS: The study sample included 1118
      inpatient/ED patients (76.6% female subjects; mean age, 62.4 years) and 41,605
      outpatients (85.8% female subjects; mean age, 52.3 years). Mean (SD) pharmacy
      costs were $2971 ($7650) for inpatient/ED patients and $1882 ($3120) for
      outpatients during the full treatment period. Index hospitalization/ED averaged
      $38,422 ($51,161). Mean all-cause 90-day follow-up costs for the inpatient/ED
      cohort were $34,100 ($71,621) and $11,345 ($34,313) for the outpatient cohort.
      IMPLICATIONS: Relative to outpatient-treated patients, inpatient/ED-treated
      patients were older, sicker, had higher costs across treatment periods, and had
      reduced antibiotic use at a lower rate during the 90-day follow-up. Strategies to
      avoid preventable inpatient/ED visits may help reduce costs in the management of
      outpatients with complicated UTIs.

PMID- 26212570
TI  - Investigation of Potential Pharmacokinetic Interactions Between Teneligliptin and
      Metformin in Steady-state Conditions in Healthy Adults.
AB  - PURPOSE: We assessed the effects of coadministration of metformin and
      teneligliptin on their pharmacokinetics in steady-state conditions relative to
      the administration of either drug alone. METHODS: This was a Phase I, single
      center, open-label, 2-way parallel-group study in healthy male and female
      subjects. Subjects in group 1 (n = 20) were administered 40 mg of teneligliptin
      once daily for 5 days, and 850 mg of metformin BID was added to ongoing
      teneligliptin for an additional 3 days. The subjects in group 2 (n = 20) were
      administered 850 mg of metformin BID for 3 days, and 40 mg of teneligliptin once
      daily was added to ongoing metformin for an additional 5 days. Pharmacokinetic
      outcomes were the AUC0-tau and Cmax of metformin and teneligliptin when
      administered alone or in combination. FINDINGS: Ten male and 10 female subjects
      participated in each group (mean +/- SD age 39.2 +/- 11.6 years [range, 19-63
      years] in group 1, 47.6 +/- 11.9 years [27-64] in group 2; mean +/- SD BMI 23.36
      +/- 2.45 in group 1, 24.56 +/- 2.54 in group 2). One female subject in each group
      was withdrawn because of an adverse event (AE) (vomiting). All 20 subjects in
      each group were included in the safety analyses, and 19 subjects in each group
      were included in the pharmacokinetic analyses. The geometric least square means
      ratio (teneligliptin plus metformin/teneligliptin alone) for Cmax and the AUC0
      tau for teneligliptin were 0.907 (90% CI, 0.853-0.965) and 1.042 (90% CI, 0.997
      1.089), respectively. The geometric least square means ratio (metformin plus
      teneligliptin/metformin alone) for the Cmax and AUC0-tau for metformin were 1.057
      (90% CI, 0.974-1.148) and 1.209 (90% CI, 1.143-1.278). The 90% CIs were within
      the prespecified threshold for equivalence (0.80-1.25), except for the AUC0-tau
      for metformin, which was increased by teneligliptin by 20% relative to metformin
      alone. In group 1, nine subjects experienced 25 AEs during treatment with
      teneligliptin alone and 10 subjects experienced 15 AEs during treatment with
      teneligliptin plus metformin. In group 2, eight subjects experienced 11 AEs
      during treatment with metformin alone and 11 subjects experienced 18 AEs during
      treatment with metformin plus teneligliptin. Two AEs in each treatment group were
      rated as severe. Results of in vitro experiments suggest that teneligliptin
      mediated inhibition of organic cation transporter-2 does not increase metformin
      exposure. IMPLICATIONS: Coadministration of teneligliptin and metformin was well
      tolerated by these healthy subjects during the 8-day treatment period.
      Coadministration with metformin did not affect the pharmacokinetics of
      teneligliptin. Although coadministration with teneligliptin increased exposure to
      metformin, this change is unlikely to be clinically relevant. European Clinical
      Trials Database identifier: 2007-001511-29.

PMID- 26212571
TI  - The meaning of gross tumor type in the aspects of cytokeratin 19 expression and
      resection margin in patients with hepatocellular carcinoma.
AB  - BACKGROUND: There is no consensus on the safe resection margin in patients with
      hepatocellular carcinoma. Surgeons decide the extent of resection according to
      residual liver function and tumor location. We investigated the influence of
      resection margin on early recurrence with respect to gross tumor type and
      expression of cytokeratin 19 (CK19). METHODS: We divided the patients into two
      groups based on the classification of The Korean Liver Cancer Study group as
      follows: group 1 included expanding and vaguely nodular types whereas group 2
      included nodular with perinodular extension, multinodular confluent, and
      infiltrative types. We classified the resection margin as narrow (0.1-0.9 cm) or
      wide (greater than 1 cm). We compared clinicopathological features and CK19
      positivity between the groups. RESULTS: Group 2 had a higher prevalence of gross
      portal vein invasion, microscopic portal vein invasion, microvessel invasion,
      satellite nodules, intrahepatic metastasis, multicentric occurrence, and
      positivity for CK19. Group 1 showed no difference in recurrence according to the
      resection margin; however, group 2 showed a higher recurrence rate in patients
      with a narrow resection margin compared with those with a wide resection margin
      (P = 0.047). Patients in group 2 with CK19 positivity showed a higher prevalence
      of microvessel invasion than those without CK19 (P = 0.026). CONCLUSIONS:
      Although our study has the limitation of a small number of cases, the data
      suggest that patients with hepatocellular carcinoma of expanding and vaguely
      nodular gross types may safely undergo surgical resection with a narrow resection
      margin and a low risk of early recurrence.

PMID- 26212572
TI  - Separation of Amyl Alcohol Isomers in ZIF-77.
AB  - The separation of pentanol isomer mixtures is shown to be very efficient using
      the nanoporous adsorbent zeolitic imidazolate framework ZIF-77. Through molecular
      simulations, we demonstrate that this material achieves a complete separation of
      linear from monobranched-and these from dibranched-isomers. Remarkably, the
      adsorption and diffusion behaviors follow the same decreasing trend, produced by
      the channel size of ZIF-77 and the guest shape. This separation based on
      molecular branching applies to alkanes and alcohols and promises to encompass
      numerous other functional groups.

PMID- 26212573
TI  - State of neonatal health care in eight countries of the SAARC region, South Asia:
      how can we make a difference?
AB  - The South Asian Association for Regional Cooperation (SAARC) is an organization
      of eight countries--Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, Sri
      Lanka and Afghanistan. The major objectives of this review are to examine trends
      and progress in newborn and neonatal health care in the region. A landscape
      analysis of the current state of neonatal mortality, stillbirths and trends over
      the years for each country and the effective interventions to reduce neonatal
      mortality and stillbirths was undertaken. A modelling exercise using the Lives
      Saved Tool (LiST) was also undertaken to determine the impact of scaling up a set
      of essential interventions on neonatal mortality and stillbirths. The findings
      demonstrate that there is an unacceptably high and uneven burden of neonatal
      mortality and stillbirths in the region which together account for 39% of global
      neonatal deaths and 41% of global stillbirths. Progress is uneven across
      countries in the region, with five of the eight SAARC countries having reduced
      their neonatal mortality rate by more than 50% since 1990, while India (43%),
      Afghanistan (29%) and Pakistan (25%) have made slower progress and will not reach
      their MDG4 targets. The major causes of neonatal mortality are intrapartum
      related deaths, preterm birth complications and sepsis which account for nearly
      80% of all deaths. The LiST analysis shows that a gradual increase in coverage of
      proven available interventions until 2020 followed by a uniform scale-up to 90%
      of all interventions until 2030 could avert 52% of neonatal deaths (0.71
      million), 29% of stillbirths (0.31 million) and achieve a 31% reduction in
      maternal deaths (0.25 million). The analysis demonstrates that the Maldives and
      Sri Lanka have done remarkably well while other countries need greater attention
      and specific focus on strategies to improve neonatal health.

PMID- 26212574
TI  - Assessment of Sacroiliitis at Diagnosis of Juvenile Spondyloarthritis by
      Radiography, Magnetic Resonance Imaging, and Clinical Examination.
AB  - OBJECTIVE: To evaluate the prevalence of sacroiliitis at diagnosis of juvenile
      spondyloarthritis (SpA) and the accuracy of physical examination and back pain to
      detect sacroiliitis, using imaging as the reference standard. METHODS: We
      performed a prospective cross-sectional study of 40 children with newly diagnosed
      juvenile SpA and 14 healthy controls. Subjects were assessed using physical
      examination, anteroposterior pelvic radiograph, and pelvic magnetic resonance
      imaging (MRI). Differences in clinical features between those children with and
      without sacroiliitis were assessed by Fisher's exact test for categorical
      variables and Wilcoxon's rank sum test for continuous variables. Accuracy of
      physical examination and back pain for detection of sacroiliitis was determined
      using MRI as the reference standard. Predicted probability of sacroiliitis was
      determined using exact multivariate logistic regression. RESULTS: Eight children
      (20%) with juvenile SpA had active sacroiliitis. Of those subjects with active
      changes on MRI, 7 of 8 (88%) also had evidence of erosions or sclerosis. Five
      children (13%) with juvenile SpA and 1 control (7%) had nonperiarticular bone
      marrow edema. Of the subjects with active sacroiliitis, only 3 (38%) reported a
      history of back pain or tenderness on palpation of the sacroiliac joints. The
      positive and negative predictive values of clinical examination features and back
      pain for detection of sacroiliitis were low. The estimated probability of having
      sacroiliitis was 0.84 (95% confidence interval 0.40-1.00) in HLA-B27-positive
      patients with an elevated C-reactive protein (CRP) level. CONCLUSION: Active
      sacroiliitis by MRI is common at diagnosis in juvenile SpA and is frequently
      asymptomatic. Children who are HLA-B27-positive and have elevated CRP levels have
      the highest probability of sacroiliitis.

PMID- 26212575
TI  - Regimen selection in the OPTIONS trial of HIV salvage therapy: drug resistance,
      prior therapy, and race-ethnicity determine the degree of regimen complexity.
AB  - BACKGROUND: Regimen selection for highly treatment-experienced patients is
      complicated. METHODS: Using a web-based utility, study team members reviewed
      antiretroviral (ARV) history and resistance data and recommended individual ARV
      regimens and nucleoside reverse transcriptase inhibitor (NRTI) options for
      treatment-experienced participants consisting of 3-4 of the following agents:
      raltegravir (RAL), darunavir (DRV)/ritonavir, tipranavir (TPV)/ritonavir,
      etravirine (ETR), maraviroc (MVC), and enfuvirtide (ENF). We evaluated team
      recommendations and site selection of regimen and NRTIs. Associations between
      baseline factors and the selection of a complex regimen (defined as including
      four ARV agents or ENF) were explored with logistic regression. RESULTS: A total
      of 413 participants entered the study. Participants initiated the first or second
      recommended regimen 86% of the time and 21% of participants started a complex
      regimen. In a multivariable model, ARV resistance to NRTI (odds ratio [OR] =
      2.2), non-nucleoside reverse transcriptase inhibitor (NNRTI, OR = 6.2) or boosted
      protease inhibitor (PI, OR = 6.6), prior use of integrase strand transfer
      inhibitor (INSTI, OR = 25), and race-ethnicity (all P <= 0.01) were associated
      with selection of a complex regimen. Black non-Hispanic (OR = 0.5) and Hispanic
      participants from the continental US (OR = 0.2) were less likely to start a
      complex regimen, compared to white non-Hispanics. CONCLUSIONS: In this multi
      center trial, we developed a web-based utility that facilitated treatment
      recommendations for highly treatment-experienced patients. Drug resistance, prior
      INSTI use, and race-ethnicity were key factors in decisions to select a more
      complex regimen.

PMID- 26212576
TI  - Non-fibrosing sclerosing epithelioid fibrosarcoma: an unusual variant.

PMID- 26212577
TI  - Control of Metal Arrays Based on Heterometallics Masquerading in Heterochiral
      Aggregations of Chiral Clothespin-Shaped Complexes.
AB  - Heterometal arrays in molecular aggregations were obtained by the spontaneous and
      ultrasound-induced gelation of organic liquids containing the chiral, clothespin
      shaped trans-bis(salicylaldiminato) d8 transition-metal complexes 1.
      Heterometallic mixtures of complexes 1 a (Pd) and 1 b (Pt) underwent strict
      heterochiral aggregation entirely due to the organic shell structure of the
      clothespin shape, with no effect of the metal cores. This phenomenon provides an
      unprecedented means of generating highly controlled heterometallic arrangements
      such as alternating sequences [(+)-Pd(-)-Pt(+)-Pd(-)-Pt???] as well as a variety
      of single metal-enriched arrays (e.g., [(+)-Pt(-)-Pd(+)-Pd(-)-Pd(+)-Pd(-)-Pd???]
      and [(+)-Pd(-)-Pt(+)-Pt(-)-Pt(+)-Pt(-)-Pt???]) upon the introduction of an
      optically active masquerading unit with a different metal core in the
      heterochiral single-metal sequence. The present method can be applied to form
      various new aggregates with optically active Pd and Pt units, to allow 1) tuning
      of the gelation ultrasound sensitivity based on the different hearing abilities
      of the metal units; 2) aggregation-induced chirality transfer between
      heterometallic species; and 3) aggregation-induced chirality enhancement. A
      mechanistic rationale is proposed for these molecular aggregations based on the
      molecular structures of the units and the morphologies of the aggregates. 

PMID- 26212578
TI  - Craniofacial Superimposition: Historical Review and Current Issues.
AB  - Methodology of craniofacial superimposition has evolved dramatically since its
      inception in the early 20th century. Contemporary approaches involve advanced
      procedures of digitization, use of video cameras, warping algorithms, skull
      positioning devices and data derived from computed tomography, radiography, and
      ultrasound technology. Applications have proven most useful in exclusion and
      casework frequency has declined in some regions in recent years as molecular
      approaches to identification have become more widely available. Additional
      research is needed to clarify the probabilities involved and to facilitate
      comparisons when the technique is employed.

PMID- 26212579
TI  - Endoscopic resection of colorectal lesions: The narrowing divide between East and
      West.
AB  - Colonic polypectomy is an effective way of reducing colon cancer mortality.
      Multiple techniques now exist for the resection of polyps, and the endoscopist
      must decide on the appropriate resection approach for individual patients and
      lesions. This decision should maximize efficacy, safety and cost-effectiveness
      and provide optimal oncological outcomes while minimizing unnecessary surgical
      treatment. Advances in endoscopic imaging technology are improving the accuracy
      of endoscopic diagnosis and allowing more precise risk assessment of colonic
      lesions. Resection technique can be tailored to the endoscopic findings.
      Diminutive (<=5 mm) and small polyps (<=9 mm) are best resected primarily by
      snare techniques. Cold snare polypectomy has proven safety, but efficacy and
      technique require further study. There is variation in techniques used for polyps
      6-20 mm in size and incomplete resection rates for conventional polypectomy may
      be considerable. Endoscopic mucosal resection (EMR) is well established, safe and
      effective for lesions without submucosal invasion (SMI); however, recurrence is a
      key limitation. Endoscopic submucosal dissection (ESD) is well established in the
      East; however, it is resource intensive and its role in lesions with a low risk
      of SMI is questionable. ESD in the West remains incompletely defined and is
      associated with high adverse event rates, but it is becoming increasingly
      available and successful as experience grows. Emerging full-thickness resection
      technologies are still in their infancy and remain experimental as a result of
      the absence of reliable closure devices and techniques. Patient-focused outcomes
      should guide technique selection. 

PMID- 26212580
TI  - Aptamer-Modified Temperature-Sensitive Liposomal Contrast Agent for Magnetic
      Resonance Imaging.
AB  - A novel aptamer modified thermosensitive liposome was designed as an efficient
      magnetic resonance imaging probe. In this paper, Gd-DTPA was encapsulated into an
      optimized thermosensitive liposome (TSL) formulation, followed by conjugation
      with AS1411 for specific targeting against tumor cells that overexpress nucleolin
      receptors. The resulting liposomes were extensively characterized in vitro as a
      contrast agent. As-prepared TSLs-AS1411 had a diameter about 136.1 nm. No obvious
      cytotoxicity was observed from MTT assay, which illustrated that the liposomes
      exhibited excellent biocompatibility. Compared to the control incubation at 37 
      degrees C, the liposomes modified with AS1411 exhibited much higher T1 relaxivity
      in MCF-7 cells incubated at 42  degrees C. These data indicate that the Gd
      encapsulated TSLs-AS1411 may be a promising tool in early cancer diagnosis. 

PMID- 26212581
TI  - Gender and age related changes in number of dopaminergic neurons in adult human
      olfactory bulb.
AB  - INTRODUCTION: Dopamine is one of the major brain neurotransmitters, and the loss
      of dopaminergic neurons in basal ganglia cause motor deficits in Parkinson's
      disease. We proposed that the difficulty in olfaction observed in the elderly may
      be due to an alteration in the number of dopaminergic neurons. MATERIALS AND
      METHODS: Sections were taken from olfactory bulbs of post-mortem tissue specimens
      of 13 humans, males and females, aged from 19 to 63 years (<=35 and >=50 years),
      with no history of neurological disorders. The tissues were fixed, embedded, cut
      on a freezing microtome, and prepared for immunohistochemical analysis using
      tyrosine hydroxylase (TH) and aromatic l-amino acid decarboxylase (AADC)
      antibodies. The number of positive neurons was counted. RESULTS: TH- and AADC
      positive cells were present in the glomerular layer. There was no significant
      difference between the numbers of TH- and AADC-positive cells, in males and
      females, and in young and elderly individuals. The quantitative analysis revealed
      that the number of TH- and AADC-positive neurons were significantly higher in
      males than in females (P<0.05). Moreover, there was a significant increase in the
      number of TH- and AADC-positive neurons in the olfactory bulbs of the elderly
      compared with young individuals (P<0.05). CONCLUSION: Factors such as gender and
      age may affect the number of dopaminergic neurons, and there is a correlation
      between increased dopaminergic neurons and olfactory performance. Moreover, the
      increase in dopaminergic cells in the olfactory bulb of the elderly may indicate
      the existence of rostral migratory stream in adult humans.

PMID- 26212582
TI  - Hippocampal GABA transporter distribution in patients with temporal lobe epilepsy
      and hippocampal sclerosis.
AB  - PURPOSE: To determine hippocampal expression of neuronal GABA-transporter (GAT-1)
      and glial GABA-transporter (GAT-3) in patients with temporal lobe epilepsy (TLE)
      and hippocampal sclerosis (HS). METHODS: Hippocampal sections were
      immunohistochemically stained for GABA-transporter 1 and GABA-transporter-3,
      followed by quantification of the immunoreactivity in the hilus by optical
      density measurements. GABA-transporter 3 positive hilar cells were counted and
      GABA-transporter protein expression in sections that included all hippocampal
      subfields was quantified by Western blot. RESULTS: The hilar GABA-transporter 1
      expression of patients with severe hippocampal sclerosis was about 7% lower
      compared to that in the mild hippocampal sclerosis/control group (p<0.001). The
      hilar GABA-transporter 3 expression was about 5% lower in the severe hippocampal
      sclerosis group than in the mild hippocampal sclerosis/control group (non
      significant). Also, severe hippocampal sclerosis samples contained 34% less (non
      significant) GABA-transporter 3 positive cells compared to that of controls.
      Protein expression as assessed by Western blot showed that GABA-transporter 1 was
      equally expressed in mild and severe hippocampal sclerosis samples, whereas GABA
      transporter 3 was reduced by about 62% in severe hippocampal sclerosis samples
      (p<0.0001). CONCLUSION: These data confirm that GABA-transporter expression is
      spatially and isoform-specific reduced and GABA-transporter 3 positive cell
      numbers are unchanged in hippocampal sclerosis. Implications for the use of
      GABAergic antiepileptic therapies in hippocampal sclerosis vs non-hippocampal
      sclerosis patients remain to be studied.

PMID- 26212583
TI  - Hepcidin levels are low during pregnancy and increase around delivery in women
      without iron deficiency - a prospective cohort study.
AB  - OBJECTIVE: To investigate hepcidin during pregnancy, delivery and postpartum in
      women with sufficient iron supplementation. METHODS: Hepcidin was measured using
      LC-MS spectroscopy in 37 women during pregnancy, delivery and postpartum period
      in this longitudinal study. RESULTS: Hepcidin was low during pregnancy and
      increased at delivery and postpartum. No correlations with inflammatory markers
      or iron metabolism were observed during pregnancy; at delivery a correlation with
      inflammatory markers was observed. CONCLUSION: During pregnancy, in women with
      sufficient iron supplementation, hepcidin is low and does not reflect iron
      status. During delivery and the postpartum period, hepcidin functions as a marker
      of inflammation.

PMID- 26212584
TI  - Postural balance and the risk of falling during pregnancy.
AB  - Pregnancy is a physiological process and many changes occur in a woman's body
      during pregnancy. These changes occur in all systems to varying degrees,
      including the cardiovascular, respiratory, genitourinary, and musculoskeletal
      systems. The hormonal, anatomical, and physiological changes occurring during
      pregnancy result in weight gain, decreased abdominal muscle strength and
      neuromuscular control, increased ligamentous laxity, and spinal lordosis. These
      alterations shift the centre of gravity of the body, altering the postural
      balance and increasing the risk of falls. Falls during pregnancy can cause
      maternal and foetal complications, such as maternal bone fractures, head
      injuries, internal haemorrhage, abruption placenta, rupture of the uterus and
      membranes, and occasionally maternal death or intrauterine foetal demise.
      Preventative strategies, such as physical exercise and the use of maternity
      support belts, can increase postural stability and reduce the risk of falls
      during pregnancy. This article reviews studies that have investigated changes in
      postural balance and risk of falling during pregnancy. 

PMID- 26212585
TI  - Is the cold loop hysteroscopic technique a myometrial sparing treatment for
      placenta accreta residuals in a puerperal uterus?
AB  - Placenta accreta is a life-threatening obstetric pathology characterized by an
      abnormal invasion of chorionic villi into the uterine wall. The management
      represents a challenge for the gynecologist, especially in patients desiring to
      preserve their fertility. Several methods have been proposed to avoid
      hysterectomy. A case of a hysteroscopic conservative management with the cold
      loop technique in a puerpera with a large mass of placenta accreta residuals is
      described. The chorionic tissue was safely detached and it was subsequently
      removed by an electric cutting loop. Even in the absence of a clear cleavage
      plane, the thermal damage of surrounding healthy myometrium and dreadful
      complications as uterine perforation due to the electric cutting loop were
      avoided. The cold-loop hysteroscopic resection seems to be a safe and effective
      choice for the treatment of retained placenta accreta in patients desiring to
      preserve fertility. Moreover, it can also be proposed to patients who need to be
      treated immediately after delivery. 

PMID- 26212586
TI  - Absolute nucleated red blood cells counts do not predict the development of
      bronchopulmonary dysplasia.
AB  - OBJECTIVE: We tested the hypothesis that infants with bronchopulmonary dysplasia
      (BPD) have higher absolute nucleated red blood cells (aNRBCs) counts at birth
      than controls as a proxy measurement of exposure to intrauterine hypoxia.
      METHODS: We studied 39 preterm infants with BPD and compared them to 39 pair
      matched controls without BPD. Criteria for exclusion in both groups included
      factors that may influence the aNRBCs at birth. RESULTS: In logistic regression,
      when pre-eclampsia, birthweight, gender, antenatal steroid therapy, 1-min Apgar
      scores, respiratory distress syndrome (RDS) (or surfactant use), intraventricular
      hemorrhage of grade 3 or more, nosocomial sepsis, patent ductus arteriosus, and
      aNRBC counts (or lymphocyte counts) were used as independent variables, and BPD
      as the dependent variable, only RDS (or its proxy measurement of surfactant use)
      and nosocomial sepsis remained included in the final analysis. CONCLUSIONS: aNRBC
      counts and lymphocyte counts do not appear to be elevated in infants that develop
      BPD, as compared to pair-matched controls without BPD. We speculate that chronic
      intrauterine hypoxia does not appear to play a major role in the pathogenesis of
      BPD. In contrast, postnatal events such as RDS and nosocomial sepsis appear to
      play a determining role in the pathogenesis of BPD.

PMID- 26212587
TI  - Predictors of eclampsia in California.
AB  - OBJECTIVE: Eclampsia is a rare yet dangerous complication of the hypertensive
      disorders of pregnancy. The objective was to elucidate the predictors of
      eclampsia in a large cohort of pregnant women with gestational hypertension or
      preeclampsia. METHODS: This was a retrospective cohort study of 143 093
      pregnancies with preeclampsia or gestational hypertension in California during
      2005-2008 of which 1719 had eclampsia. Predictors included race/ethnicity,
      parity, chronic hypertension (CHTN), diabetes mellitus, gestational diabetes
      mellitus (GDM), preterm delivery <32 weeks, maternal age >= 35, maternal age <=
      20, socioeconomic status, education, and <5 prenatal visits. Univariate and
      multivariate analyses were performed. RESULTS: Factors that increased the risk of
      eclampsia included Black (OR 1.46 [1.19-1.80]) and Hispanic race (OR 1.56 [1.35
      1.79]), nulliparity (OR 1.59 [1.42-1.77]), maternal age <= 20 (OR 1.85 [1.61
      2.11]), preterm delivery <32 weeks (OR 1.41 [1.16-1.70]), and <5 prenatal care
      visits (1.74 [1.46-2.07]). Factors that decreased the risk of eclampsia included
      CHTN (OR 0.06 [0.03-0.10]), GDM (OR 0.80 [0.67-0.96]), maternal age >= 35 (OR
      0.70 [0.59-0.82]), and college education (OR 0.83 [0.74-0.94]). CONCLUSIONS:
      Black and Hispanic race, nulliparity, maternal age <= 20, preterm delivery <32
      weeks, and <5 prenatal care visits increase the risk of eclampsia while CHTN,
      GDM, maternal age >= 35, and college education are protective. The protective
      effect of CHTN is the most striking. The mechanisms are likely different and
      warrant further investigation.

PMID- 26212588
TI  - Is documentation of TOLAC counseling a good measure of quality of care?
AB  - OBJECTIVE: The objective of this study is to determine whether chart
      documentation of patient counseling on trial of labor after cesarean (TOLAC)
      during prenatal care is associated with patient knowledge of risks and benefits
      of TOLAC and repeat cesarean delivery (RCD). STUDY DESIGN: Prenatal patients
      eligible for TOLAC completed a questionnaire that assessed their knowledge of
      basic maternal and neonatal risks and benefits of TOLAC versus planned repeat
      cesarean delivery. Patient electronic medical records were reviewed for
      documentation of TOLAC counseling. Women were included at both early and late
      time points in pregnancy to include those who both had and had not undergone
      counseling. RESULTS: Patients with documented completed TOLAC counseling did not
      perform better on the knowledge survey. Patients who had documentation of
      counseling on specific subjects such as TOLAC success rates, risk of uterine
      rupture, and downstream health risks of cesarean section were no more likely to
      answer questions on these topics correctly than patients without counseling.
      However, patients with documented completed counseling generally felt that they
      were well informed. CONCLUSION: Chart documentation of TOLAC counseling was not
      correlated with patient knowledge. Patients may not be gaining the knowledge from
      counseling that providers believe is important for informed decision making.

PMID- 26212589
TI  - Catalytic Synthesis of N-Unprotected Piperazines, Morpholines, and
      Thiomorpholines from Aldehydes and SnAP Reagents.
AB  - Commercially available SnAP (stannyl amine protocol) reagents allow the
      transformation of aldehydes and ketones into a variety of N-unprotected
      heterocycles. By identifying new ligands and reaction conditions, a robust
      catalytic variant that expands the substrate scope to previously inaccessible
      heteroaromatic substrates and new substitution patterns was realized. It also
      establishes the basis for a catalytic enantioselective process through the use of
      chiral ligands. 

PMID- 26212590
TI  - Inferential comprehension of 3-6 year olds within the context of story grammar: a
      scoping review.
AB  - BACKGROUND: The ability to make inferences plays a crucial role in reading
      comprehension and the educational success of school-aged children. However, it
      starts to unfold much earlier than school entry and literacy. Given that it is
      likely to be targeted in speech language therapy, it would be useful for
      clinicians to have access to information about a developmental sequence of
      inferential comprehension. Yet, at this time, there is no clear proposition of
      the way in which this ability develops in young children prior to school entry.
      AIMS: To reduce the knowledge gap with regards to inferential comprehension in
      young children by conducting a scoping review of the literature. The two
      objectives of this research are: (1) to describe typically developing children's
      comprehension of causal inferences targeting elements of story grammar, with the
      goal of proposing milestones in the development of this ability; and (2) to
      highlight key elements of the methodology used to gather this information in a
      paediatric population. METHODS & PROCEDURES: A total of 16 studies from six
      databases that met the inclusion criteria were qualitatively analysed in the
      context of a scoping review. This methodological approach was used to identify
      common themes and gaps in the knowledge base to achieve the intended objectives.
      MAIN CONTRIBUTION: Results permit the description of key elements in the
      development of six types of causal inference targeting elements of story grammar
      in children between 3 and 6 years old. Results also demonstrate the various
      methods used to assess this ability in young children and highlight particularly
      interesting procedures for use with this younger population. CONCLUSIONS: These
      findings point to the need for additional studies to understand this ability
      better and to develop strategies to stimulate an evidence-based developmental
      sequence in children from an early age.

PMID- 26212592
TI  - The Association of Interpersonal and Intrapersonal Emotional Experiences with Non
      Suicidal Self-Injury in Young Adults.
AB  - Non-suicidal self-injury (NSSI), the intentional damage to body tissue without
      the intent to die, is a prevalent public health problem in the U.S. and around
      the world. The current study sought to identify intrapersonal (emotional
      reactivity) and interpersonal (emotional expressiveness to others) correlates of
      NSSI in order to provide insight into how to best tailor prevention and treatment
      efforts. Four hundred and forty nine college students were surveyed about various
      psychological characteristics as well as engagement in NSSI. Results indicated
      that those who have difficulty expressing emotions are at an increased risk for
      NSSI even after controlling for depressive symptoms and that emotional
      expressiveness acts as a partial mediator between depression and NSSI. Emotional
      expressiveness should be a target of treatment among people who engage in NSSI. 

PMID- 26212591
TI  - Characterization of RNA silencing components in the plant pathogenic fungus
      Fusarium graminearum.
AB  - The RNA interference (RNAi) plays a critical role in gene regulation in a variety
      of eukaryotic organisms. However, the role of RNAi remains largely unclear in
      plant pathogenic fungi. In this study, we explored the roles of core components
      of the RNAi pathway in Fusarium graminearum, the major causal agent of wheat head
      blight. Our results demonstrated that the hairpin RNA (hpRNA) can efficiently
      silence the expression level of target gene, and the argonaute protein FgAgo1 and
      dicer protein FgDicer2 are important in this silencing process. RNAi machinery
      was not involved in growth, abiotic stress and pathogenesis in F. graminearum
      under tested conditions. We firstly applied high-throughput sequencing technology
      to elucidate small RNA (17-40 nucleotides) (sRNA) transcriptome in F.
      graminearum, and found that a total of forty-nine micro-like-RNA (milRNA)
      candidates were identified in the wild-type and ?FgDICER2, and twenty-four of
      them were FgDicer2-dependent. Fg-milRNA-4 negatively regulated expression of its
      target gene. Taken together, our results indicated that the hpRNA-induced gene
      silencing was a valuable genetic tool for exploring gene function in F.
      graminearum. FgAgo1 and FgDicer2 proteins played a critical role in the hpRNA
      mediated gene silencing process. In addition, FgDicer2 was involved in sRNA
      transcription and milRNA generation in this fungus. 

PMID- 26212593
TI  - Fine Tuning of beta-Peptide Foldamers: a Single Atom Replacement Holds Back the
      Switch from an 8-Helix to a 12-Helix.
AB  - Cyclic homologated amino acids are important building blocks for the construction
      of helical foldamers. N-aminoazetidine-2-carboxylic acid (AAzC), an aza analogue
      of trans-2-aminocyclobutanecarboxylic acid (tACBC), displays a strong hydrazino
      turn conformational feature, which is proposed to act as an 8-helix primer. tACBC
      oligomers bearing a single N-terminal AAzC residue were studied to evaluate the
      ability of AAzC to induce and support an 8-helix along the oligopeptide length.
      While tACBC homooligomers assume a dominant 12-helix conformation, the aza-primed
      oligomers preferentially adopt a stabilized 8-helix conformation for an oligomer
      length up to 6 residues. The (formal) single-atom exchange at the N terminus of a
      tACBC oligomer thus contributes to the sustainability of the 8-helix, which
      resists the switch to a 12-helix. This effect illustrates atomic-level
      programmable design for fine tuning of peptide foldamer architectures. 

PMID- 26212594
TI  - Computer-aided pelvic reduction frame for anatomical closed reduction of unstable
      pelvic fractures.
AB  - Traditional closed reductions of unstable pelvic fractures are mainly performed
      by surgeons using manual manipulation and subjective verification based on intra
      operative roentgenography. It is difficult to perform an accurate closed
      reduction because of a lack of adequate knowledge of the displacement patterns
      and an inability to apply the reduction in correct direction. Using the concept
      of the remote center of motion mechanism and computer-aided design software, we
      developed a pelvic reduction frame for use in anatomical closed reductions of
      unstable pelvic fractures. With three-dimensional reconstruction technique and
      the matrix algorithm, the spatial orientation of the displaced hemipelvis can be
      calculated and deconstructed into several rotational and translational movements
      that can be completed with the frame. To verify the accuracy of this system, the
      rotations were repeated 10 times in arbitrary degrees and directions. After the
      matrix is calculated, the displaced hemipelvis can be reduced to the anatomical
      position using our frame. The maximum residual translational and rotational
      displacements were less than 5 mm and 4 degrees, which indicated the accuracy of
      this system. The maximum average residual translation and rotation were 1.87 mm
      in Z-axis (ranging: 4.63-0.1 mm) and 1.1 degrees around Y-axis (ranging: 3.81
      0.13 degrees), respectively. Only the Z-axial translation showed a statistically
      significant difference (p < 0.05). In conclusion, the proposed pelvic reduction
      frame could be a useful tool for the anatomical reduction of unstable pelvic
      fractures.

PMID- 26212595
TI  - Defensive K channel.

PMID- 26212596
TI  - Psychosocial acceptance of cleft patients: has something changed?
AB  - OBJECTIVE: The main purpose of this study was to analyse the reactions of a panel
      (non-cleft adults) when observing cleft lip morphology. Although rehabilitation
      of cleft lip and palate is improving, there are still indications of social
      rejection of cleft patients by the people around them. Polarity profiles have
      been used since 1973 to measure social distance with regard to cleft patients.
      Because rehabilitation results and education of the society have improved in
      recent decades, we investigated whether social distance has been affected.
      SETTING: The setting of this study is the Department of Oral,
      Craniomaxillofacial, and Facial Plastic Surgery, University Hospital of Leipzig,
      Germany PATIENTS AND PARTICIPANTS: Using a cross-sectional study design, we
      enrolled a sample of adult laypersons (n = 273). For the survey, we followed the
      concept of photograph presentation and questionnaire investigation reported by
      Sergl and Schmid (1973). We presented anonymised frontal and profile pictures of
      the faces of 50 cleft patients and asked the laypersons to specify social
      distance. Three predictor variables (layperson gender, profession and year of
      evaluation) were grouped. RESULTS: Although social distance has reduced during
      the last 40 years, life situations which require emotional proximity still cause
      some concern. Professional background and gender affect laypersons' attitudes.
      CONCLUSION: Although rehabilitation of cleft lip and palate is much better than
      40 years ago, social distance remains a problem in society. It is necessary to
      improve both results of rehabilitation of cleft patients and social acceptance by
      the people around them.

PMID- 26212597
TI  - Predictors for Reporting of Dietary Assessment Methods in Food-based Randomized
      Controlled Trials over a Ten-year Period.
AB  - The importance of monitoring dietary intake within a randomized controlled trial
      becomes vital to justification of the study outcomes when the study is food
      based. A systematic literature review was conducted to determine how dietary
      assessment methods used to monitor dietary intake are reported and whether
      assisted technologies are used in conducting such assessments. OVID and
      ScienceDirect databases 2000-2010 were searched for food-based, parallel,
      randomized controlled trials conducted with humans using the search terms
      "clinical trial," "diet$ intervention" AND "diet$ assessment," "diet$ method$,"
      "intake," "diet history," "food record," "food frequency questionnaire," "FFQ,"
      "food diary," "24-hour recall." A total of 1364 abstracts were reviewed and 243
      studies identified. The size of the study and country of origin appear to be the
      two most common predictors of reporting both the dietary assessment method and
      details of the form of assessment. The journal in which the study is published
      has no impact. Information technology use may increase in the future allowing
      other methods and forms of dietary assessment to be used efficiently. 

PMID- 26212598
TI  - An intermediary enhances out-group trust and in-group profit expectation of
      Chinese but not Australians.
AB  - In this research, we made a theoretical distinction between direct and
      intermediary-mediated trust situations, and conducted a cross-cultural (Chinese
      vs. Australians) investment trust game to test the overlooked effects of an
      intermediary on investors' trust decisions, with respect to how much to invest in
      and expect from trustees. Compared to situations of direct trust, a nominal
      intermediary increased the number of Chinese investors expecting in-group
      trustees to repay a profit on their investments (Hypothesis 1) and raised their
      level of investment in out-group trustees (Hypothesis 2). These results applied
      to Chinese, but not Australians in support of the proposal that a nominal
      intermediary would serve as a cue to activate different cultural stereotypes of
      the functions and meanings of an intermediary with respect to trust and
      expectation of reciprocity. Coexisting with these culture-specific effects of an
      intermediary, the minimal categorisation of people into in-group and out-group on
      trivial grounds leads to a highly significant in-group favouritism in investment
      levels of both Chinese and Australians (Hypothesis 3).

PMID- 26212599
TI  - Korea hemophilia foundation registry trends 1991-2012: patient registry,
      demographics, health services utilization.

PMID- 26212600
TI  - The meta-analytic big bang.
AB  - This article looks at the impact of meta-analysis and then explores why meta
      analysis was developed at the time and by the scholars it did in the social
      sciences in the 1970s. For the first problem, impact, it examines the impact of
      meta-analysis using citation network analysis. The impact is seen in the
      sciences, arts and humanities, and on such contemporaneous developments as
      multilevel modeling, medical statistics, qualitative methods, program evaluation,
      and single-case design. Using a constrained snowball sample of citations, we
      highlight key articles that are either most highly cited or most central to the
      systematic review network. Then, the article examines why meta-analysis came to
      be in the 1970s in the social sciences through the work of Gene Glass, Robert
      Rosenthal, and Frank Schmidt, each of whom developed similar theories of meta
      analysis at about the same time. The article ends by explaining how Simonton's
      chance configuration theory and Campbell's evolutionary epistemology can
      illuminate why meta-analysis occurred with these scholars when it did and not in
      medical sciences.

PMID- 26212601
TI  - Synthesis, antiviral activity and structure-activity relationship of 1-(1-aryl
      4,5-dihydro-1H-imidazoline)-3-chlorosulfonylureas and products of their
      cyclization.
AB  - Novel 1-(1-aryl-4,5dihydro-1H-imidazoline)-3-chlorosulfonylourea derivatives 3a
      3f were synthesized in the reaction of 1-aryl-4,5-dihydro-1H-imidazol-2-amines
      with chlorosulfonyl isocyanate. The second series of compounds 4a-4f was prepared
      from the respective 1-(1-aryl-4,5-dihydro-1H-imidazoline)-3-chlorsulfonylureas 3a
      3f and 1,1'-carbonyldiimidazole (CDI). The selected compounds were tested for
      their activity against Herpes simplex virus and coxsackievirus B3 (CVB3). It was
      determined that three derivatives, i.e 3d, 4a and 4d are active against Herpes
      simplex virus (HSV-1). Compounds 3d and 4c are active against CVB3. Their
      favorable activity can be primarily attributed to their low lipophilicity values.
      Moreover, the lack of substituent in the phenyl moiety or 4-methoxy substitution
      can be considered as the most beneficial for the antiviral activity. 

PMID- 26212602
TI  - Correlations between two different methods to score bleeding and the relationship
      with plaque in systemically healthy young adults.
AB  - AIM: To evaluate the correlation between bleeding on marginal probing (BOMP) and
      bleeding on pocket probing (BOPP), and the correlation of both bleeding indices
      with plaque. MATERIALS AND METHODS: This cross-sectional study screened 336
      participants, from which 268 were eligible for examination and analysis. Bleeding
      and plaque indices were assessed by single examiners, at six sites per tooth.
      RESULTS: The mean percentage of sites per individual with bleeding on marginal
      probing, bleeding on pocket probing and dental plaque were 19.9%, 51.2% and 32.2%
      respectively. In the quadrants where the margin was probed before the pocket, a
      4.6 percentage points higher bleeding tendency with BOPP was observed (p < 0.05).
      At a site level, the correlation coefficients of plaque and bleeding on marginal
      probing and bleeding on pocket probing were 0.19 and 0.20 respectively. Both
      bleeding indices were also shown to be correlated (r = 0.89, fixed effect model).
      CONCLUSION: The prevalence of bleeding upon probing is influenced by the scoring
      method that is used for the diagnosis. Probing the bottom of the pocket results
      in significantly more bleeding than running a probe along the margin.

PMID- 26212603
TI  - Holistic assessment of women with hyperemesis gravidarum: A randomised controlled
      trial.
AB  - BACKGROUND: Hyperemesis gravidarum or severe nausea and vomiting of pregnancy
      affects women's physical, social and psychological wellbeing and often requires
      frequent hospital admissions. Current standard care may be too medically focussed
      to meet all of women's complex needs. AIM: The aim of this study is to test where
      using a validated questionnaire, the Hyperemesis Impact of Symptoms tool,
      delivered by a nurse to assess the overall effect of hyperemesis on an individual
      woman's life and to provide advice tailored to her specific needs, will help her
      cope better with her symptoms and reduce admissions to hospital. DESIGN: This
      study was a two arm randomised controlled trial in which women with hyperemesis
      from four hospitals were randomly allocated to one of two groups: (1) usual care
      and (2) usual care plus assessment with the Hyperemesis Impact of Symptoms
      questionnaire and a care plan tailored to their responses. PARTICIPANTS AND
      METHODS: Recruitment was from women who were admitted with hyperemesis
      gravidarum; diabetic women or those over 14 weeks gestation were excluded. Those
      who consented completed questionnaires to assess their quality of life and the
      severity of symptoms at baseline and at three time points over the following 6
      weeks. RESULTS: Women's average social functioning, Hyperemesis Impact of Symptom
      scores and average number of admissions were not significantly different between
      either group. The average number of days in hospital for the questionnaire and
      tailored plan group was significantly lower, 4.97, compared with 6.14 in the
      usual care group. Using the questionnaire to plan individualised care was not
      associated with significant reduction in health care costs. CONCLUSION: Using the
      Hyperemesis Impact of Symptoms questionnaire to tailor a care plan to address
      women's individual needs was not associated with any significant improvements in
      the quality of life. The cost effectiveness analysis did not indicate that the
      questionnaire is cost saving. The Hyperemesis Impact of Symptoms questionnaire is
      a practical tool for nurses and midwives to assess the overall impact of
      hyperemesis gravidarum on the individual and could be useful for assessing
      symptoms and evaluating physical, social and psychological changes following
      treatment in either clinical or research settings.

PMID- 26212604
TI  - A structural equation model of turnover for a longitudinal survey among early
      career registered nurses.
AB  - BACKGROUND: Key predictors of early career nurses' turnover are job satisfaction,
      organizational commitment, job search, intent to stay, and shock (back injuries)
      based on the literature review and our previous research. Existing research has
      often omitted one of these key predictors. OBJECTIVES: The purpose of this study
      in a sample of early career nurses was to compare predictors of turnover to
      nurses' actual turnover at two time points in their careers. DESIGN: A multi
      state longitudinal panel survey of early career nurses was used to compare a
      turnover model across two time periods. The sample has been surveyed five times.
      PARTICIPANTS: The sample was selected using a two-stage sample of registered
      nurses nested in 51 metropolitan areas and nine non-metropolitan, rural areas in
      34 states and the District of Columbia. METHODS: The associations between key
      predictors of turnover were tested using structural equation modeling and data
      from the earliest and latest panels in our study. We used predictors from the
      respondents who replied to the Wave-1 survey in 2006 and their turnover status
      from Wave 2 in 2007 (N=2386). We compared these results to the remaining
      respondents' predictors from Wave 4 in 2011 and their turnover status in Wave 5
      in 2013 (N=1073). We tested and found no effect for missingness from Wave 1-5 and
      little evidence of attrition bias. RESULTS: Strong support was found for the
      relationships hypothesized among job satisfaction, organizational commitment,
      intent to stay, and turnover, with some support for shock and search in the Wave
      1-2 sample. However, for Wave 4-5 sample (n=1073), none of the paths through
      search were significant, nor was the path from shock to turnover. CONCLUSIONS:
      Nurses in the second analysis who had matured longer in their career did not have
      a significant response to search or shock (back injuries), which may indicate how
      easily experienced registered nurses find new jobs and/or accommodation to jobs
      requiring significant physicality. Nurse turnover is a major concern for
      healthcare organizations because of its costs and related outcomes. The relevant
      strength and relationships of these key turnover predictors will be informative
      to employers for prioritizing strategies to retain their registered nurse
      workforce. We need more research on programs that implement changes in the work
      environment that impact these two outcomes, as well as research that focuses on
      the relevant strength or impact to help administrators prioritize translation of
      results.

PMID- 26212605
TI  - Nickel Allergy and Our Children's Health: A Review of Indexed Cases and a View of
      Future Prevention.
AB  - Nickel is the leading cause of allergic contact dermatitis (ACD) from early
      childhood through adolescence. Studies have shown that skin piercings and other
      nickel-laden exposures can trigger the onset of nickel ACD in those who are
      susceptible. Nickel ACD causes a vast amount of cutaneous disease in children.
      Cases of nickel ACD in children have been reported in peer-reviewed literature
      from 28 states. Common items that contain inciting nickel include jewelry, coins,
      zippers, belts, tools, toys, chair studs, cases for cell phones and tablets, and
      dental appliances. The diagnosis of nickel ACD has been routinely confirmed by
      patch testing in children older than 6 months suspected of ACD from nickel.
      Unlike in Europe, there are no mandatory restrictions legislated for nickel
      exposure in the United States. Denmark has demonstrated that regulation of the
      nickel content in metals can lower the risk of ACD and the associated health care
      related costs that arise from excess nickel exposure. To further awareness, this
      article reviews the prominent role of nickel in pediatric skin disease in the
      United States. It discusses the need for a campaign by caretakers to reduce
      nickel-related morbidity. Lastly, it promotes the model of European legislation
      as a successful intervention in the prevention of nickel ACD.

PMID- 26212606
TI  - TRAIL-Induced Caspase Activation Is a Prerequisite for Activation of the
      Endoplasmic Reticulum Stress-Induced Signal Transduction Pathways.
AB  - It is well known that tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL)-induced apoptosis can be initially triggered by surface death receptors
      (the extrinsic pathway) and subsequently amplified through mitochondrial
      dysfunction (the intrinsic pathway). However, little is known about signaling
      pathways activated by the TRAIL-induced endoplasmic reticulum (ER) stress
      response. In this study, we report that TRAIL-induced apoptosis is associated
      with the endoplasmic reticulum (ER) stress response. Human colorectal carcinoma
      HCT116 cells were treated with TRAIL and the ER stress-induced signal
      transduction pathway was investigated. During TRAIL treatment, expression of ER
      stress marker genes, in particular the BiP (binding immunoglobulin protein) gene,
      was increased and activation of the PERK (PKR-like ER kinase)-eIF2alpha
      (eukaryotic initiation factor 2alpha)-ATF4 (activating transcription factor 4)
      CHOP (CCAAT-enhancer-binding protein homologous protein) apoptotic signal
      transduction pathway occurred. Experimental data from use of a siRNA (small
      interfering RNA) technique, caspase inhibitor, and caspase-3-deficient cell line
      revealed that TRAIL-induced caspase activation is a prerequisite for the TRAIL
      induced ER stress response. TRAIL-induced ER stress was triggered by caspase-8
      mediated cleavage of BAP31 (B cell receptor-associated protein 31). The
      involvement of the proapoptotic PERK-CHOP pathway in TRAIL-induced apoptosis was
      verified by using a PERK knockout (PERK(-/-)) mouse embryo fibroblast (MEF) cell
      line and a CHOP(-/-) MEF cell line. These results suggest that TRAIL-induced the
      activation of ER stress response plays a role in TRAIL-induced apoptotic death.

PMID- 26212607
TI  - Hindered Glymes for Graphite-Compatible Electrolytes.
AB  - Organic carbonate mixtures are used almost exclusively as lithium battery
      electrolyte solvents. The linear compounds (dimethyl carbonate, diethyl
      carbonate, ethyl methyl carbonate) act mainly as thinner for the more viscous and
      high-melting ethylene carbonate but are the least stable component and have low
      flash points; these are serious handicaps for lifetime and safety. Polyethers
      (glymes) are useful co-solvents, but all formerly known representatives solvate
      Li(+) strongly enough to co-intercalate in the graphite negative electrode and
      exfoliate it. We have put forward a new electrolyte composition comprising a
      polyether to which a bulky tert-butyl group is attached ("hindered glyme"), thus
      completely preventing co-intercalation while maintaining good conductivity. This
      alkyl-carbonate-free electrolyte shows remarkable cycle efficiency of the
      graphite electrode, not only at room temperature, but also at 50 and 70  degrees
      C in the presence of lithium bis(fluorosulfonimide). The two-ethylene-bridge
      hindered glyme has a high boiling point and a flash point of 80  degrees C, a
      considerable advantage for safety. 

PMID- 26212608
TI  - Comparison of autologous versus allogeneic epithelial-like stem cell treatment in
      an in vivo equine skin wound model.
AB  - BACKGROUND AIMS: Several studies report beneficial effects of autologous and
      allogeneic stem cells on wound healing. However, no comparison between autologous
      versus allogeneic epithelial-like stem cells (EpSCs) has been made so far. For
      this reason, we first hypothesize that both EpSC types enhance wound healing in
      comparison to vehicle treatment and untreated controls. Second, on the basis of
      other studies, we hypothesized that there would be no difference between
      autologous and allogeneic EpSCs. METHODS: Twelve full-thickness skin wounds were
      created in six horses. Each horse was subjected to (i) autologous EpSCs, (ii)
      allogeneic EpSCs, (iii) vehicle treatment or (iv) untreated control. Wound
      evaluation was performed at day 3, 7 and 14 through wound exudates and at week 1,
      2 and 5 through biopsies. RESULTS: Wound circumference and surface were
      significantly smaller in autologous EpSC-treated wounds. A significantly lower
      amount of total granulation tissue (overall) and higher vascularization (week 1)
      was observed after both EpSC treatments. Significantly more major
      histocompatibility complex II-positive and CD20-positive cells were noticed in
      EpSC-treated wounds at week 2. In autologous and allogeneic groups, the number of
      EpSCs in center biopsies was low after 1 week (11.7% and 6.1%), decreased to 7.6%
      and 1.7%, respectively (week 2), and became undetectable at week 5. CONCLUSIONS:
      These results confirm the first hypothesis and partially support the second
      hypothesis. Besides macroscopic improvements, both autologous and allogeneic
      EpSCs had similar effects on granulation tissue formation, vascularization and
      early cellular immune response.

PMID- 26212609
TI  - Wound-healing potential of human umbilical cord blood-derived mesenchymal stromal
      cells in vitro--a pilot study.
AB  - BACKGROUND AIMS: Our previous studies demonstrated that human bone marrow-derived
      mesenchymal stromal cells have great potential for wound healing. However, it is
      difficult to clinically utilize cultured stem cells. Recently, human umbilical
      cord blood-derived mesenchymal stromal cells (hUCB-MSCs) have been commercialized
      for cartilage repair as a first cell therapy product that uses allogeneic stem
      cells. Should hUCB-MSCs have a superior effect on wound healing as compared with
      fibroblasts, which are the main cell source in current cell therapy products for
      wound healing, they may possibly replace fibroblasts. The purpose of this in
      vitro study was to compare the wound-healing activity of hUCB-MSCs with that of
      fibroblasts. METHODS: This study was particularly designed to compare the effect
      of hUCB-MSCs on diabetic wound healing with those of allogeneic and autologous
      fibroblasts. Healthy (n = 5) and diabetic (n = 5) fibroblasts were used as the
      representatives of allogeneic and autologous fibroblasts for diabetic patients in
      the control group. Human UCB-MSCs (n = 5) were used in the experimental group.
      Cell proliferation, collagen synthesis and growth factor (basic fibroblast growth
      factor, vascular endothelial growth factor and transforming growth factor-beta)
      production were compared among the three cell groups. RESULTS: Human UCB-MSCs
      produced significantly higher amounts of vascular endothelial growth factor and
      basic fibroblast growth factor when compared with both fibroblast groups. Human
      UCB-MSCs were superior to diabetic fibroblasts but not to healthy fibroblasts in
      collagen synthesis. There were no significant differences in cell proliferation
      and transforming growth factor-beta production. CONCLUSIONS: Human UCB-MSCs may
      have greater capacity for diabetic wound healing than allogeneic or autologous
      fibroblasts, especially in angiogenesis.

PMID- 26212610
TI  - Generation of potent dendritic cells with improved migration ability through p
      cofilin and sarco/endoplasmic reticulum Ca(2+) transport ATPase 2 regulation.
AB  - BACKGROUND AIMS: It is important to improve the migratory ability of dendritic
      cells (DCs) and to increase DC potency for successful DC-based cancer
      immunotherapy. The intracellular Ca(2+) signaling pathway has an important role
      on the regulation of DC migration. Our preliminary studies revealed that
      sarco/endoplasmic reticulum Ca(2+) transport ATPase 2 (SERCA2) expression was
      inversely related to DC migratory capacity, and the expression level of p-cofilin
      and SERCA2 on mature DCs showed a counter-trend. METHODS: We selected the
      appropriate six maturation cocktails on the basis of the expression levels of
      SERCA2 and p-cofilin and investigated the functional characteristics and
      migratory capacity of mature DCs. Among the these six maturation cocktails, DCIFN
      gamma/IL-1beta/Poly-I:C showed potent type 1 immune response with interleukin
      (IL)-12p70 production and strong Th1-polarization, and this DC elicited strong
      antigen-specific cytotoxic T-lymphocyte responses. RESULTS: Interestingly, DCIFN
      gamma/IL-1beta/Poly-I:C showed lower expression of SERCA2 and higher expression
      of p-cofilin compared with those matured with the use of other cocktails. In
      vitro migration assay showed that DCs matured with the use of this maturation
      cocktail had significantly increased migratory ability compared with alphaDC1s
      and other DCs. CONCLUSIONS: Interferon-gamma, IL-1beta and Poly-I:C maturation
      cocktail may be used in the field of cancer immunotherapy to generate potent
      immune-stimulatory DCs with improved type 1 immune response and migration
      capacity.

PMID- 26212611
TI  - Low-cost generation of Good Manufacturing Practice-grade CD19-specific chimeric
      antigen receptor-expressing T cells using piggyBac gene transfer and patient
      derived materials.
AB  - BACKGROUND AIMS: Protocols for the production of CD19-specific chimeric antigen
      receptor (CAR19) T cells are often complex and expensive because of the use of
      retroviral and lentiviral vectors or the need for CAR19 T-cell enrichment. We
      aimed to simplify the generation of CAR19 T cells from the peripheral blood of
      normal donors and patients using the piggyBac transposon system of gene
      modification. METHODS: We varied electroporation voltage, cytokines and
      stimulation conditions for the generation and expansion of CAR19 T cells over a 3
      week culture period. RESULTS: Using optimized electroporation voltage,
      interleukin-15 alone and co-culturing CAR T cells with peripheral blood
      mononuclear cells, we were able to expand CAR19 T-cell cultures by up to 765-fold
      over 3 weeks in normal donors and 180-fold in patients with B-cell malignancies.
      Final median CAR19 expression of 72% was seen in normal donors, and 81% was seen
      in patients with acute lymphoblastic leukaemia, chronic lymphocytic leukemia or
      non-Hodgkin lymphoma. CAR19 T cells produced interferon gamma on stimulation with
      CD19(+) cell lines and efficiently lysed both CD19(+) cell lines and primary
      leukemia cells. In addition, combining CAR expression with an inducible caspase
      safety switch allowed elimination of CAR19 T cells by the application of a small
      molecule dimerizer. DISCUSSION: We have produced a simple, inexpensive and easily
      adoptable protocol for the generation of CAR19 T cells suitable for use in
      clinical trials using the piggyBac transposon system. This provides a robust
      platform for further enhancing the T-cell product and testing new CAR
      technologies.

PMID- 26212612
TI  - Neurodevelopmental outcome after neonatal perforator stroke.
AB  - AIM: To assess outcome after neonatal perforator stroke in the largest cohort to
      date. METHOD: Survivors from a cohort of children diagnosed with neonatal
      perforator stroke using cranial ultrasound or magnetic resonance imaging were
      eligible for inclusion. Recovery and Recurrence Questionnaire score, presence of
      cerebral palsy (CP), and crude outcome were assessed, specifically (1) the
      ability to walk independently, (2) participation in regular education, and (3)
      the presence of epilepsy. RESULTS: Thirty-seven patients (20 males, 17 females)
      aged 3 to 14 years (mean age 8y) were included in the study: 14 with isolated
      single perforator stroke, four with multiple isolated perforator strokes, and 19
      with additional brain injury. Out of 18 children with isolated perforator
      stroke(s), four had CP, one could not walk independently, and one developed
      epilepsy. The posterior limb of the internal capsule was involved in four out of
      18 patients; three of these patients had CP. Of 19 children with additional brain
      injury, 11 had CP and three were not able to walk independently. Three out of
      nine children with concomitant cortical middle cerebral artery stroke developed
      epilepsy. INTERPRETATION: Perforator stroke patterns can be of use in predicting
      long-term outcome and for guiding counselling and surveillance. Motor outcome was
      favourable in children with isolated perforator stroke(s), except when the
      posterior limb of the internal capsule was involved.

PMID- 26212613
TI  - Evolution of dosage compensation under sexual selection differs between X and Z
      chromosomes.
AB  - Complete sex chromosome dosage compensation has more often been observed in XY
      than ZW species. In this study, using a population genetic model and the chicken
      transcriptome, we assess whether sexual conflict can account for this difference.
      Sexual conflict over expression is inevitable when mutation effects are
      correlated across the sexes, as compensatory mutations in the heterogametic sex
      lead to hyperexpression in the homogametic sex. Coupled with stronger selection
      and greater reproductive variance in males, this results in slower and less
      complete evolution of Z compared with X dosage compensation. Using expression
      variance as a measure of selection strength, we find that, as predicted by the
      model, dosage compensation in the chicken is most pronounced in genes that are
      under strong selection biased towards females. Our study explains the pattern of
      weak dosage compensation in ZW systems, and suggests that sexual selection plays
      a major role in shaping sex chromosome dosage compensation. 

PMID- 26212615
TI  - Effect of antimicrobial peptide on the dynamics of phosphocholine membrane: role
      of cholesterol and physical state of bilayer.
AB  - Antimicrobial peptides are universal in all forms of life and are well known for
      their strong interaction with the cell membrane. This makes them a popular target
      for investigation of peptide-lipid interactions. Here we report the effect of
      melittin, an important antimicrobial peptide, on the dynamics of membranes based
      on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid in both the solid gel
      and fluid phases. To probe the phase transition, elastic neutron intensity
      temperature scans have been carried out on DMPC-based unilamellar vesicles (ULV)
      with and without melittin. We have found that addition of a small amount (0.2
      mol%) melittin eliminates the steep fall in the elastic intensity at 296 K
      associated with the solid gel to fluid phase transition, which is observed for
      pure DMPC vesicles. Quasielastic neutron scattering (QENS) experiments have been
      carried out on DMPC ULV in the solid gel and fluid phases with and without 0.2
      mol% melittin. The data analysis invariably shows the presence of lateral and
      internal motions of the DMPC molecule. We found that melittin does have a
      profound effect on the dynamics of lipid molecules, especially on the lateral
      motion, and affects it in a different way, depending on the phase of the
      bilayers. In the solid gel phase, it acts as a plasticizer, enhancing the lateral
      motion of DMPC. However, in the fluid phase it acts as a stiffening agent,
      restricting the lateral motion of the lipid molecules. These observations are
      consistent with the mean squared displacements extracted from the elastic
      intensity temperature scans. Their importance lies in the fact that many membrane
      processes, including signaling and energy transduction pathways, are controlled
      to a great extent by the lateral diffusion of lipids in the membrane. To
      investigate the effect of melittin on vesicles supplemented with cholesterol,
      QENS experiments have also been carried out on DMPC ULV with cholesterol in the
      presence and absence of 0.2 mol% melittin. Remarkably, the effects of melittin on
      the membrane dynamics disappear in the presence of 20 mol% cholesterol. Our
      measurements indicate that the destabilizing effect of the peptide melittin on
      membranes can be mitigated by the presence of cholesterol. This study might
      provide new insights into the mechanism of action of antimicrobial peptides and
      their selective toxicity towards foreign microorganisms. 

PMID- 26212614
TI  - Live imaging of endogenous Ca2+/calmodulin-dependent protein kinase II in neurons
      reveals that ischemia-related aggregation does not require kinase activity.
AB  - The Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) forms 12meric
      holoenzymes. These holoenzymes cluster into larger aggregates within neurons
      under ischemic conditions and in vitro when ischemic conditions are mimicked.
      This aggregation is thought to be mediated by interaction between the regulatory
      domain of one kinase subunit with the T-site of another kinase subunit in a
      different holoenzyme, an interaction that requires stimulation by Ca(2+) /CaM and
      nucleotide for its induction. This model makes several predictions that were
      verified here: Aggregation in vitro was reduced by the CaMKII inhibitors tatCN21
      and tatCN19o (which block the T-site) as well as by KN93 (which is CaM
      competitive). Notably, these and previously tested manipulations that block
      CaMKII activation all reduced aggregation, suggesting an alternative mechanism
      that instead requires kinase activity. However, experiments with the nucleotide
      competitive broad-spectrum kinase inhibitors staurosporin and H7 showed that this
      is not the case. In vitro, staurosporine and H7 enabled CaMKII aggregation even
      in the absence of nucleotide. Within rat hippocampal neurons, an intra-body
      enabled live monitoring of endogenous CaMKII aggregation. This aggregation was
      blocked by tatCN21, but not by staurosporine, even though both effectively
      inhibit CaMKII activity. These results support the mechanistic model for CaMKII
      aggregation and show that kinase activity is not required. CaMKII aggregation is
      prevented by inhibiting kinase activity with mutations (red italics; shown
      previously) or inhibitors (red bold; shown here), indicating requirement of
      kinase activity. However, we show here that nucleotide-competitive inhibitors
      (green) allow CaMKII aggregation (including endogenous CaMKII within neurons),
      demonstrating that kinase activity is not required and supporting the current
      mechanistic model for CaMKII aggregation.

PMID- 26212616
TI  - Tuning of intramolecular charge transfer properties and charge distributions in
      ferrocene-appended catechol derivatives by chemical substitution.
AB  - In this study, we report intramolecular charge transfer (ICT) properties and
      charge distributions in a series of FcC derivatives (FcC = 4
      ferrocenylcatecholate where Fc = ferrocene and C = catecholate). This series
      consists of a previously reported complex FcV (4-ferrocenylveratrole) and newly
      synthesized complexes FcA (4-ferrocenylcatechol bis(acetate) and
      Pt((t)Bu2bpy)(FcC) ((t)Bu2bpy = 4,4'-di-tert-butyl-2,2'-dipyridyl). An
      electrochemical analysis of Pt((t)Bu2bpy)(FcC) using cyclic voltammetry revealed
      two well-defined, reversible waves which were assigned to the sequential
      oxidation of the Pt((t)Bu2bpy)(C) and Fc moieties. The potential splitting
      between the waves (524 mV) indicated that there was an electronic interaction
      between both moieties. ICT property and charge distribution of
      [Pt((t)Bu2bpy)(FcC)](+) were rationalized by comparison with the [FcV](+) and
      [FcA](+) (4-ferrocenylcatechol bis(acetate)). DFT calculations and UV-vis-NIR
      spectroscopy revealed that [Pt((t)Bu2bpy)(FcC)](+), [FcV](+), and [FcA](+) were
      ferrocenium (Fc(+))-centered rather than semiquinone ligand-centered and that
      these complexes exhibited ICT transition bands from the catechol-derivatized
      framework to the Fc(+) moiety in the near infrared (NIR) region. Both the
      electronic coupling parameter (HAB) and delocalization parameter (alpha)
      increased in value as the electron-donating strength of the substituent groups in
      the catechol-derivatized framework increased (OCOCH3 ([FcA](+)) < OCH3 ([FcV](+))
      < O(-) ([Pt((t)Bu2bpy)(FcC)](+))). The electronic interactions between the
      organometallic center and the non-innocent framework were tuned by changing the
      substituents. The potential energy surfaces of the Fc(+) derivatives, obtained
      using two-state Marcus-Hush theory, can be modulated by changing the energy level
      of the molecular orbitals of the appended catechol-derivatized moieties. 

PMID- 26212617
TI  - Activation of new replication foci under conditions of replication stress.
AB  - DNA damage, binding of drugs to DNA or a shortage of nucleotides can decrease the
      rate or completely halt the progress of replication forks. Although the global
      rate of replication decreases, mammalian cells can respond to replication stress
      by activating new replication origins. We demonstrate that a moderate level of
      stress induced by inhibitors of topoisomerase I, commencing in early, mid or late
      S-phase, induces activation of new sites of replication located within or in the
      immediate vicinity of the original replication factories; only in early S some of
      these new sites are also activated at a distance greater than 300 nm. Under high
      stress levels very few new replication sites are activated; such sites are
      located within the original replication regions. There is a large variation in
      cellular response to stress - while in some cells the number of replication sites
      increases even threefold, it decreases almost twofold in other cells. Replication
      stress results in a loss of PCNA from replication factories and a twofold
      increase in nuclear volume. These observations suggest that activation of new
      replication origins from the pool of dormant origins within replication cluster
      under conditions of mild stress is generally restricted to the original
      replication clusters (factories) active at a time of stress initiation, while
      activation of distant origins and new replication factories is suppressed.

PMID- 26212618
TI  - Dynamics of a Global Zoonotic Research Network Over 33 Years (1980-2012).
AB  - OBJECTIVE: The increasing rate of outbreaks in humans of zoonotic diseases
      requires detailed examination of the education, research, and practice of animal
      health and its connection to human health. This study investigated the
      collaboration network of different fields engaged in conducting zoonotic research
      from a transdisciplinary perspective. METHODS: Examination of the dynamics of
      this network for a 33-year period from 1980 to 2012 is presented through the
      development of a large scientometric database from Scopus. In our analyses we
      compared several properties of these networks, including density, clustering
      coefficient, giant component, and centrality measures over time. We also elicited
      patterns in different fields of study collaborating with various other fields for
      zoonotic research. RESULTS: We discovered that the strongest collaborations
      across disciplines are formed among the fields of medicine; biochemistry,
      genetics, and molecular biology; immunology and microbiology; veterinary;
      agricultural and biological sciences; and social sciences. Furthermore, the
      affiliation network is growing overall in terms of collaborative research among
      different fields of study such that more than two-thirds of all possible
      collaboration links among disciplines have already been formed. CONCLUSIONS: Our
      findings indicate that zoonotic research scientists in different fields (human or
      animal health, social science, earth and environmental sciences, engineering)
      have been actively collaborating with each other over the past 11 years.

PMID- 26212619
TI  - Primary Malignant Melanoma of the Esophagus: A Case Report and Review of the
      Literature.
AB  - BACKGROUND Primary malignant melanoma of the esophagus (PMME) is a rare cancer
      with a poor prognosis. It is often difficult to differentiate from non-epithelial
      malignant tumors, and immunohistochemical staining may be needed to diagnose the
      condition. The mainstay of treatment is usually surgical with curative or
      palliative intent, since radio- and chemotherapy do not really improve the
      outcome. The average survival rate after surgery is 34.5 months. At the time of
      diagnosis, 40-80% of cases have local regional lymph node metastases. CASE REPORT
      The case of a 67-year-old male patient with PMME is reported. He presented with
      progressive dysphagia. A computerized tomography was performed in which a
      polypoid mass was observed in the distal esophagus. It was originally suspected
      to be an adenocarcinoma, but was subsequently correctly diagnosed by
      immunohistochemical staining with HMB-45 antibody and by the presence of S-100
      protein. A subtotal esophagectomy was performed. CONCLUSIONS Very few cases of
      PMME have been reported in the literature and there is only limited clinical
      experience with this disease. Therefore, it is very difficult to establish clear
      criteria for clinical recognition of this type of melanoma. Early
      histopathological confirmation of the character is essential for further
      treatment in case of confirmation of malignancy. 

PMID- 26212620
TI  - [New Applications and Indications for Contrast-Enhanced Sonography in
      Endovascular Aortic Repair].
AB  - After edovascular repair of infrarenal aortic aneurysms (EVAR) endoleaks may
      occur necessitating further therapy. Therefore a reliable method for follow-up
      imaging after EVAR for detection and control of endoleaks is of high importance.
      Contrast-enhanced sonography (CEUS) does not require the application of
      nephrotoxid contrast media and does not stress the patient. CEUS is increasingly
      used and enables a quick, non-invasive follow-up examination for patient after
      EVAR. In addition, interventions as therapy for endoleaks may be executed using
      ultrasound. Initial experience with CEUS-guided aortic stenting shows that the
      amount of contrast media as well as X-ray time may be reduced. 

PMID- 26212621
TI  - Antiservice Within the Medical Service Encounter: Lessons for Radiologists Beyond
      Service Recovery.
AB  - Recent modifications in the metrics for reimbursement have reinforced the
      importance of radiology service-delivery experiences of patients. Evaluating
      current radiology practices calls for reflection on the various touch points with
      patients, as well as their overall satisfaction. If problems occur during
      encounters, service failure, or lack of satisfactory medical experiences can be
      transformed through service recovery, whereby patients-as-customers are given
      chances to voice their concerns, and health care providers across the spectrum
      can work together to resolve problematic issues. This paper takes a systemic view
      of the patient experience as embedded in the care continuum, recognizing that
      different beliefs, attitudes, and behaviors of members of the health care team
      can negatively affect or sabotage patient satisfaction. Although radiologists are
      only one of many roles in the care continuum, recommendations are discussed for
      how they can integrate service satisfaction as a pervasive communal goal among
      all health care team members. 

PMID- 26212622
TI  - Magnitude of Impact, Overall and on Subspecialties, of Transitioning in Radiology
      from ICD-9 to ICD-10 Codes.
AB  - PURPOSE: Converting the nation's International Classification of Diseases (ICD)
      diagnosis coding system, from 14,025 ICD-9 to 69,823 ICD-10 codes, is projected
      to have enormous financial and operational implications. We aimed to assess the
      magnitude of impact that this code conversion will have on radiology claims.
      METHODS: The most frequently billed ICD-9 diagnosis codes for 588,523 radiology
      claims from five hospitals and affiliated outpatient sites during a 12-month
      period were mapped to matching ICD-10 codes using a Medicare-endorsed tool. The
      code-conversion impact factor was calculated for the entire radiology system, and
      each individual subspecialty division. RESULTS: Of all ICD-9 codes, only 3,407
      (24.3%) were used to report any primary diagnosis. Of all claims, 50% were billed
      using just 37 (0.3%) primary codes; 75% with 131 (0.5%), and 90% with 348 (2.5%).
      Those 348 ICD-9 codes mapped onto 2,048 ICD-10 codes (5.9-fold impact),
      representing just 2.9% of all ICD-10 codes. By subspecialty, the conversion
      impact factor varied greatly, from 1.1 for breast (11 ICD-9 to 12 ICD-10 codes)
      to 28.8 for musculoskeletal imaging (146 to 4,199). The community division,
      reflecting a general practice mix, saw a conversion impact factor of 5.8 (254 to
      1,471). CONCLUSIONS: Fewer than 3% of all ICD-9 and ICD-10 codes are used to
      report an overwhelming majority of all radiology claims. Although the number of
      commonly used codes will expand 5.9-fold overall, musculoskeletal imaging will
      experience a projected 28.8-fold explosion. Radiology practices should target
      their ICD educational and operational conversion efforts in an evidence-based
      manner.

PMID- 26212623
TI  - Lower temperature at the wound edge detected by thermography predicts undermining
      development in pressure ulcers: a pilot study.
AB  - Undermined pressure ulcers (PUs) are troublesome complications that are likely to
      delay wound healing. Early skin incision and debridement can prevent the
      deterioration of undermined PUs, thus it is necessary to identify devitalised
      tissue areas to determine the appropriate timing for such interventions. This
      retrospective cohort study evaluated whether a lower temperature at the wound
      edge than the wound bed and periwound skin, detected by thermography, can predict
      undermining development in PUs 1 week after the assessment. Twenty-two
      participants with category III, IV, or unstageable PUs who were examined by
      interdisciplinary PU team and were followed up for at least two consecutive weeks
      were analysed. We found 9/11 PUs without a lower temperature at the wound edge
      did not develop undermining development, whereas 8/11 PUs with the lower
      temperature did develop undermining. The relative risk of undermining development
      after 1 week in PUs with the lower temperature was 4.00 (95% confidence
      intervals: 1.08-14.7). The sensitivity, specificity, positive predictive value
      and negative predictive value were 0.80, 0.75, 0.73 and 0.81, respectively. A
      thermal imaging assessment focusing on a lower temperature pattern at the wound
      edge may provide sufficient information to predict undermining development. 

PMID- 26212624
TI  - Is there an association between the level of grandiose narcissism severity of
      psychopathology?
AB  - BACKGROUND: Narcissism is a personality trait associated with both psychological
      health and resilience as well as with aggression and interpersonal problems. AIM:
      This study compares levels of total narcissism and subscale scores in inpatients,
      outpatients and a community sample. METHODS: Inpatients (N = 186) were recruited
      from consecutively admitted patients to two closed units, and the outpatient
      group (N = 144) consisted of patients attending a psychiatric outpatient clinic.
      The patients and a normative community sample (N = 437) all filled in the
      Narcissistic Personality Inventory questionnaire (NPI-29). RESULTS: The NPI total
      and subscales scores showed considerable gender differences. Among men only the
      Uniqueness/Entitlement subscale showed significant group differences, with
      inpatients showing higher mean score than the two other groups. Among women three
      factors, Leadership/Power, Superiority/Arrogance, and Uniqueness/ Entitlement,
      showed significant differences between the different levels of psychopathology.
      The outpatient female group regularly had the lowest group mean scores. The NPI
      29 scores of the normative group showed weak internal consistencies. CONCLUSION:
      Our hypothesis of a significant association between mean levels of total
      narcissism and subscale scores and severity of psychopathology was not supported.

PMID- 26212625
TI  - Application and optimization of the tenderization of pig Longissimus dorsi muscle
      by adenosine 5'-monophosphate (AMP) using the response surface methodology.
AB  - Based on single factor experiments, NaCl concentration, adenosine 5'
      monophosphate (AMP) concentration and temperature were selected as independent
      variables for a three-level Box-Behnken experimental design, and the shear force
      and cooking loss were response values for regression analysis. According to the
      statistical models, it showed that all independent variables had significant
      effects on shear force and cooking loss, and optimal values were at the NaCl
      concentration of 4.15%, AMP concentration of 22.27 mmol/L and temperature of
      16.70 degrees C, which was determined with three-dimensional response surface
      diagrams and contour plots. Under this condition, the observed shear force and
      cooking loss were 0.625 kg and 8.07%, respectively, exhibiting a good agreement
      with their predicted values, showing the good applicability and feasibility of
      response surface methodology (RSM) for improving pork tenderness. Compared with
      control pig muscles, AMP combined with NaCl treatment demonstrated significant
      effects on improvement of meat tenderness and reduction of cooking loss.
      Therefore, AMP could be regarded as an effective tenderization agent for pork. 

PMID- 26212626
TI  - Heavy menstrual bleeding on rivaroxaban.

PMID- 26212627
TI  - Endothelial function and cardiovascular risk in patients with inflammatory bowel
      disease in remission phase.

PMID- 26212628
TI  - Targeted Microbubbles for Ultrasound Mediated Short Hairpin RNA Plasmid
      Transfection to Inhibit Survivin Gene Expression and Induce Apoptosis of Ovarian
      Cancer A2780/DDP Cells.
AB  - Nonviral gene transfer by ultrasound-targeted microbubble destruction (UTMD) is
      an promising technique for RNA interference (RNAi) therapy. Targeting silence
      survivin gene may provide an important therapeutic option for patients with
      ovarian cancer. However, UTMD mediated RNAi therapy typically uses nontargeted
      microbubbles with suboptimal gene transfection efficiency. In this work, a LHRHa
      targeted microbubble agent and recombinant expression plasmid of shRNA targeting
      survivin gene (pshRNA survivin) were constructed for UTMD mediated pshRNA
      survivin therapy in ovarian cancer A2780/DDP cells that express LHRH receptors.
      The targeted microbubbles (TMBs) mixed with the pshRNA survivin were added to
      cultured ovarian cancer cells followed by ultrasound exposure (1 MHz, 0.5
      W/cm(2)) for 30 s. After transfection for 48 h, the expression of survivin mRNA
      and protein were (0.36 +/- 0.036) and (0.05 +/- 0.02), respectively. The cell
      proliferation inhibitory rates at 24, 48, and 72 h after treatment are (42.08 +/-
      3.20)%, (54.60 +/- 1.02)%, and (74.25 +/- 2.14)%, respectively, and the apoptosis
      rate was (28.99 +/- 2.70)%. The expression of apoptosis related protein caspase-9
      and caspase-3 were (0.95 +/- 0.09) and (2.6 +/- 0.21). In comparison with the
      other treatment groups, ultrasound mediation of targeted microbubbles yielded
      higher RNAi efficiency and higher cell apoptosis rate and cell proliferation
      inhibitory rate (p < 0.05). Our experiment verifies the hypothesis that
      ultrasound mediation of targeted microbubbles will enhance RNAi efficiency in
      ovarian cancer cells. This novel method for RNA interference represents a
      powerful, promising no viral technology that can be used in the tumor gene
      therapy and research. 

PMID- 26212629
TI  - Expression of myosin VIIA in the developing chick inner ear neurons.
AB  - The auditory-vestibular ganglion (AVG) is formed by the division of otic placode
      derived neuroblasts, which then differentiate into auditory and vestibular
      afferent neurons. The developmental mechanisms that regulate neuronal cell fate
      determination, axonal pathfinding and innervation of otic neurons are poorly
      understood. The present study characterized the expression of myosin VIIA, along
      with the neuronal markers, Islet1, NeuroD1 and TuJ1, in the developing avian ear,
      during Hamburger-Hamilton (HH) stages 16-40. At early stages, when neuroblasts
      are delaminating from the otic epithelium, myosin VIIA expression was not
      observed. Myosin VIIA was initially detected in a subset of neurons during the
      early phase of neuronal differentiation (HH stage 20). As the AVG segregates into
      the auditory and vestibular portions, myosin VIIA was restricted to a subset of
      vestibular neurons, but was not present in auditory neurons. Myosin VIIA
      expression in the vestibular ganglion was maintained through HH stage 33 and was
      downregulated by stage 36. Myosin VIIA was also observed in the migrating
      processes of vestibular afferents as they begin to innervate the otic epithelium
      HH stage 22/23. Notably, afferents targeting hair cells of the cristae were
      positive for myosin VIIA while afferents targeting the utricular and saccular
      maculae were negative (HH stage 26-28). Although previous studies have reported
      that myosin VIIA is restricted to sensory hair cells, our data shows that myosin
      VIIA is also expressed in neurons of the developing chick ear. Our study suggests
      a possible role for myosin VIIA in axonal migration/pathfinding and/or
      innervation of vestibular afferents. In addition, myosin VIIA could be used as an
      early marker for vestibular neurons during the development of the avian AVG. 

PMID- 26212630
TI  - Longitudinal determinants of walking, moderate, and vigorous physical activity in
      Australian adults.
AB  - OBJECTIVE: To explore longitudinal (demographic, socioeconomic, health and
      psychological) determinants of walking, moderate and vigorous physical activity.
      METHODS: The sample included 11,133 adult participants (5913 women; 5220 men)
      taken from the Household, Income and Labour Dynamics in Australia (HILDA)
      project. Demographic, socioeconomic, health and psychological data were collected
      in 2010 and estimates of walking, moderate and vigorous physical activity were
      collected in 2014. RESULTS: Participant age, sex, occupational status, working
      hours, and neighbourhood remoteness were most strongly related to total physical
      activity. Psychological traits (personality and distress sensitivity) were
      unrelated to subsequent physical activity, and health-related behaviours (diet
      variables and smoking frequency) were moderately related. Participant
      demographics (age and sex) were most important for vigorous intensity physical
      activity, and socioeconomic factors (e.g., neighbourhood remoteness, total
      income, occupational status, weekly hours worked) were most important for
      moderate intensity physical activity. CONCLUSIONS: This investigation shows that
      demographic, socioeconomic, and health-related variables are important
      determinants of adult physical activity levels, and that demographic and
      socioeconomic factors might become more or less important for different
      intensities of physical activity.

PMID- 26212631
TI  - Systematic review of sedentary behavior and cognitive development in early
      childhood.
AB  - OBJECTIVE: To comprehensively review observational and experimental studies
      examining the relationship between sedentary behavior and cognitive development
      during early childhood (birth to 5years). METHOD: Electronic databases were
      searched in July, 2014 and no limits were imposed on the search. Included studies
      had to be peer-reviewed, published, and meet the a priori determined population
      (apparently healthy children aged birth to 5years), intervention (duration,
      types, and patterns of sedentary behavior), comparator (various durations, types,
      or patterns of sedentary behavior), and outcome (cognitive development) study
      criteria. Data extraction occurred in October and November 2014 and study quality
      and risk of bias were assessed in December 2014. RESULTS: A total of 37 studies,
      representing 14,487 participants from nine different countries were included.
      Thirty-one studies used observational study designs and six studies used
      experimental study designs. Across study designs, increased or higher screen time
      (most commonly assessed as television viewing (TV)), reading, child-specific TV
      content, and adult-specific TV content had detrimental (negative) associations
      with cognitive development outcomes for 38%, 0%, 8%, and 25% of associations
      reported, respectively, and beneficial (positive) associations with cognitive
      development outcomes for 6%, 60%, 13%, and 3% of associations reported,
      respectively. Ten studies were moderate quality and 27 studies were weak quality.
      CONCLUSIONS: The type of sedentary behavior, such as TV versus reading, may have
      different impacts on cognitive development in early childhood. Future research
      with reliable and valid tools and adequate sample sizes that examine multiple
      cognitive domains (e.g., language, spatial cognition, executive function, memory)
      are needed. Registration no. CRD42014010004.

PMID- 26212633
TI  - Effects of changes in permit-to-purchase handgun laws in Connecticut and Missouri
      on suicide rates.
AB  - OBJECTIVE: In 2013, more than 40,000 individuals died from suicide in the United
      States. Restricting access to lethal means has the potential to prevent suicide,
      as suicidal thoughts are often transient. Permit-to-purchase (PTP) laws for
      handguns could potentially reduce suicides by making it more difficult for
      persons at risk of suicide to purchase a handgun. METHODS: We used a quasi
      experimental research design with annual, state-level suicide data to evaluate
      changes to PTP laws in Connecticut and Missouri. Data were analyzed for 1981
      2012. We used synthetic control modeling as the primary method to estimate policy
      effects. This methodology provided better prediction of pre-PTP-law-change trends
      in the two states with PTP law changes than econometric models and is thus likely
      to provide more accurate estimates of policy effects. RESULTS: The synthetic
      control model estimated a 15.4% reduction in firearm suicide rates associated
      with Connecticut's PTP law. Missouri's PTP law repeal was associated with a 16.1%
      increase in firearm suicide rates. Evidence that PTP laws were associated with
      non-firearm suicide rates was mixed in Connecticut and negative in Missouri.
      CONCLUSION: The findings are consistent with prior research linking firearm
      availability to increased risk of suicide and lower suicide risks associated with
      PTP handgun laws.

PMID- 26212632
TI  - Caring for pregnant opioid abusers in Vermont: A potential model for non-urban
      areas.
AB  - Opioid addiction is no longer a primarily urban problem. As dependence on heroin
      and prescription pain relievers has become a significant issue in rural areas,
      the need for effective treatment of opioid-dependent pregnant women and their
      neonates has grown accordingly. In addition to the adverse perinatal outcomes
      associated with opioid addiction in pregnant women, the high costs of caring for
      these mothers and their babies motivate efforts to develop appropriate treatment
      models. We found that integration and coordination of services that promote
      maternal recovery and ability to parent are key requirements for treatment of
      opioid dependence during pregnancy. Unfortunately, lack of experience and
      resources makes such coordination a real challenge in rural areas. In this
      review, we discuss how we managed the challenges of developing a comprehensive
      program for treatment of opioid dependence during pregnancy. In addition, we
      outline our approach for facilitating the development of community-based programs
      to help these patients and families in rural regions of Vermont. Close
      relationships between our tertiary care center, local hospitals, community health
      care infrastructure, and legislators bolstered our efforts. In particular,
      appreciation for the severity and importance of the opioid-dependence problem in
      Vermont among health care providers and state legislators was paramount for our
      success in developing a state-wide treatment program. This approach can inform
      similar efforts in other rural regions of the United States, and has great
      potential to improve both access and quality of care for women struggling with
      opioid dependence. 

PMID- 26212637
TI  - A Needs Assessment of Sub-Sahara African National Hypertension Organizations for
      Hypertension Prevention and Control Programs.

PMID- 26212636
TI  - Safety assessment for ethanol-based topical antiseptic use by health care
      workers: Evaluation of developmental toxicity potential.
AB  - Ethanol-based topical antiseptic hand rubs, commonly referred to as alcohol-based
      hand sanitizers (ABHS), are routinely used as the standard of care to reduce the
      presence of viable bacteria on the skin and are an important element of infection
      control procedures in the healthcare industry. There are no reported indications
      of safety concerns associated with the use of these products in the workplace.
      However, the prevalence of such alcohol-based products in healthcare facilities
      and safety questions raised by the U.S. FDA led us to assess the potential for
      developmental toxicity under relevant product-use scenarios. Estimates from a
      physiologically based pharmacokinetic modeling approach suggest that occupational
      use of alcohol-based topical antiseptics in the healthcare industry can generate
      low, detectable concentrations of ethanol in blood. This unintended systemic dose
      probably reflects contributions from both dermal absorption and inhalation of
      volatilized product. The resulting internal dose is low, even under hypothetical,
      worst case intensive use assumptions. A significant margin of exposure (MOE)
      exists compared to demonstrated effect levels for developmental toxicity under
      worst case use scenarios, and the MOE is even more significant for typical
      anticipated occupational use patterns. The estimated internal doses of ethanol
      from topical application of alcohol-based hand sanitizers are also in the range
      of those associated with consumption of non-alcoholic beverages (i.e., non
      alcoholic beer, flavored water, and orange juice), which are considered safe for
      consumers. Additionally, the estimated internal doses associated with expected
      exposure scenarios are below or in the range of the expected internal doses
      associated with the current occupational exposure limit for ethanol set by the
      Occupational Safety and Health Administration. These results support the
      conclusion that there is no significant risk of developmental or reproductive
      toxicity from repeated occupational exposures and high frequency use of ABHSs or
      surgical scrubs. Overall, the data support the conclusion that alcohol-based hand
      sanitizer products are safe for their intended use in hand hygiene as a critical
      infection prevention strategy in healthcare settings. 

PMID- 26212638
TI  - Free tissue transfer to the traumatized upper extremity: Risk factors for
      postoperative complications in 282 cases.
AB  - BACKGROUND: Complex traumatic upper extremity injuries frequently possess
      compromised local vasculature or extensive defects that are not amenable to local
      flap reconstruction. Free tissue transfer is required to provide adequate soft
      tissue coverage. The present study aimed to evaluate risk factors that contribute
      to postoperative complications and flap loss in complex upper extremity
      reconstruction. METHODS: Retrospective chart review was performed for all
      patients undergoing free tissue transfer for upper extremity reconstruction from
      1976 to 2001. Data collected included patient demographic characteristics, timing
      of reconstruction, location of injury, fracture characteristics, operative
      interventions, and postoperative complications. Statistical analysis was
      performed using chi(2) and Fisher exact tests. RESULTS: In total, 238 patients
      underwent 285 free tissue transfers and met inclusion criteria, from which 3 were
      excluded because of inadequate information (n = 282). Extremities were repaired
      within 24 h (75 cases; 27%), in days 2-7 (32 cases; 12%), or after day 7 (172
      cases; 62%). Timing of reconstruction did not significantly affect postoperative
      outcomes. Proximal location of injury was significantly associated with
      superficial (relative risk [RR], 6.5; P < .01) and deep infection (RR, 5.3; P <
      .01), and osteomyelitis (RR, 4.0; P < .01), although not with flap failure (P =
      .30). Presence of an open fracture was significantly associated with developing
      superficial (RR, 3.1; P = .01) and deep (RR, 1.9; P < .01) infection, as well as
      osteomyelitis (RR, 1.6; P < .01). Having a closed fracture did not negatively
      influence postoperative outcomes. CONCLUSIONS: This study supports the safety of
      early free tissue transfer for reconstruction of traumatized upper extremities.
      Injuries proximal to the elbow and open fracture were associated with a
      significantly higher infection rate. Gustilo grade IIIC fractures, need for
      interpositional vein grafts, and anastomotic revision at index operation resulted
      in significantly higher risk of flap loss, whereas the presence of fracture,
      fracture fixation, and injury location were not predictors of flap failure.

PMID- 26212639
TI  - Quantitative disease resistance to the bacterial pathogen Xanthomonas campestris
      involves an Arabidopsis immune receptor pair and a gene of unknown function.
AB  - Although quantitative disease resistance (QDR) is a durable and broad-spectrum
      form of resistance in plants, the identification of the genes underlying QDR is
      still in its infancy. RKS1 (Resistance related KinaSe1) has been reported
      recently to confer QDR in Arabidopsis thaliana to most but not all races of the
      bacterial pathogen Xanthomonas campestris pv. campestris (Xcc). We therefore
      explored the genetic bases of QDR in A. thaliana to diverse races of X.
      campestris (Xc). A nested genome-wide association mapping approach was used to
      finely map the genomic regions associated with QDR to Xcc12824 (race 2) and
      XccCFBP6943 (race 6). To identify the gene(s) implicated in QDR, insertional
      mutants (T-DNA) were selected for the candidate genes and phenotyped in response
      to Xc. We identified two major QTLs that confer resistance specifically to
      Xcc12824 and XccCFBP6943. Although QDR to Xcc12824 is conferred by At5g22540
      encoding for a protein of unknown function, QDR to XccCFBP6943 involves the well
      known immune receptor pair RRS1/RPS4. In addition to RKS1, this study reveals
      that three genes are involved in resistance to Xc with strikingly different
      ranges of specificity, suggesting that QDR to Xc involves a complex network
      integrating multiple response pathways triggered by distinct pathogen molecular
      determinants.

PMID- 26212641
TI  - ?

PMID- 26212640
TI  - Genome-wide mutational spectra analysis reveals significant cancer-specific
      heterogeneity.
AB  - Cancer is widely recognized as a genetic disease in which somatic mutations are
      sequentially accumulated to drive tumor progression. Although genomic landscape
      studies are informative for individual cancer types, a comprehensive comparative
      study of tumorigenic mutations across cancer types based on integrative data
      sources is still a pressing need. We systematically analyzed ~10(6) non
      synonymous mutations extracted from COSMIC, involving ~8000 genome-wide screened
      samples across 23 major human cancers at both the amino acid and gene levels. Our
      analysis identified cancer-specific heterogeneity that traditional nucleotide
      variation analysis alone usually overlooked. Particularly, the amino acid
      arginine (R) turns out to be the most favorable target of amino acid alteration
      in most cancer types studied (P < 10(-9), binomial test), reflecting its
      important role in cellular physiology. The tumor suppressor gene TP53 is mutated
      exclusively with the HYDIN, KRAS, and PTEN genes in large intestine, lung, and
      endometrial cancers respectively, indicating that TP53 takes part in different
      signaling pathways in different cancers. While some of our analyses corroborated
      previous observations, others indicated relevant candidates with high priority
      for further experimental validation. Our findings have many ramifications in
      understanding the etiology of cancer and the underlying molecular mechanisms in
      particular cancers. 

PMID- 26212642
TI  - ?

PMID- 26212643
TI  - ?

PMID- 26212645
TI  - ?

PMID- 26212644
TI  - ?

PMID- 26212646
TI  - ?

PMID- 26212648
TI  - ?

PMID- 26212647
TI  - ?

PMID- 26212649
TI  - ?

PMID- 26212650
TI  - ?

PMID- 26212651
TI  - ?

PMID- 26212652
TI  - ?

PMID- 26212653
TI  - Prospective memory and frontal lobe function.
AB  - The study sought to examine the role of frontal lobe functioning in focal
      prospective memory (PM) performance and its relation to PM deficit in older
      adults. PM and working memory (WM) differences were studied in younger aged (n =
      21), older aged (n = 20), and frontal injury (n = 14) groups. An event-based
      focal PM task was employed and three measures of WM were administered. The
      younger aged group differed from the other two groups in showing significantly
      higher scores on PM and on one of the WM measures, but there were no differences
      at a statistically significant level between the older aged group and the frontal
      injury groups on any of the memory measures. There were, however, some
      differences in correlations with a WM measure between groups. It is concluded
      that there are similarities and differences in the deficits in PM between older
      adults and patients with frontal lobe injury on focal as well as nonfocal PM
      tasks. 

PMID- 26212654
TI  - miR-29c regulates NAV3 protein expression in a transgenic mouse model of
      Alzheimer's disease.
AB  - The microRNA-29 family (miRNA-29s) has three mature members, miR-29a, miR-29b and
      miR-29c, which have been implicated in the regulation of the pathogenesis of
      Alzheimer's disease (AD). The miR-29 family members exhibit differential
      regulation in various diseases and different subcellular distribution. In the
      present study, we initially investigated differential expression of miR-29c in
      the hippocampus and the frontal cortex of the young APPswe/PSDeltaE9 mouse brain,
      accompanied by inverse expression of neurone navigator 3 (NAV3), a regulator of
      axon guidance. We observed that miR-29c directly mediated downregulation of NAV3
      protein expression in vitro. The mouse NAV3 mRNA has a functional miR-29c binding
      site in the 3' UTR, which localized in the position between 830-836 bp of 3'UTR
      region, slightly different from human NAV3 mRNA binding site. These observations
      suggest that miR-29c may be involved in neurodegenerative processes by regulating
      NAV3 expression in the young AD mouse.

PMID- 26212655
TI  - Synthesis of ammonia directly from wet air using Sm(0.6)Ba(0.4)Fe(0.8)Cu(0.2)O(3
      delta) as the catalyst.
AB  - Ammonia was directly synthesised from wet air at 400  degrees C at atmospheric
      pressure. A new perovskite Sm(0.6)Ba(0.4)Fe(0.8)Cu(0.2)O(3-delta) was used as the
      electrocatalyst for electrochemical synthesis of ammonia. Ammonia formation rates
      of 9.19 * 10(-7) mol s(-1) m(-2) and 1.53 * 10(-6) mol s(-1) m(-2) were obtained
      at 400  degrees C when wet air and wet N2 were introduced into a simple single
      chamber reactor, respectively. The perovskite catalyst is low cost compared to
      the previously reported Ru/MgO and Pt/C catalysts. This experiment indicates that
      ammonia can be directly synthesised from wet air, a very promising simple
      technology for sustainable synthesis of ammonia in the future.

PMID- 26212656
TI  - Pulmonary artery pulsatility index predicts right ventricular failure after left
      ventricular assist device implantation.
AB  - BACKGROUND: Right ventricular failure (RVF) is a major cause of morbidity and
      mortality after left ventricular assist device (LVAD) implantation. The pulmonary
      artery pulsatility index (PAPi) is a novel hemodynamic index that predicts RVF in
      the setting of myocardial infarction, although it has not been shown to predict
      RVF after LVAD implantation. METHODS: We performed a retrospective, single-center
      analysis to examine the utility of the PAPi in predicting RVF and RV assist
      device (RVAD) implantation in 85 continuous-flow LVAD recipients. We performed a
      multivariate logistic regression analysis incorporating previously identified
      predictors of RVF after LVAD placement, including clinical and echocardiographic
      variables, to determine the independent effect of PAPi in predicting RVF or RVAD
      after LVAD placement. RESULTS: In this cohort, the mean PAPi was 3.4 with a
      standard deviation of 2.9. RVF occurred in 33% of patients, and 11% required a
      RVAD. Multivariate analysis, adjusting for age, blood urea nitrogen (BUN), and
      Interagency Registry for Mechanically Assisted Circulatory Support profile,
      revealed that higher PAPi was independently associated with a reduced risk of
      RVAD placement (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.07-0.89).
      This relationship did not change significantly when echocardiographic measures
      were added to the analysis. Stratifying the analysis by the presence of inotropes
      during catheterization revealed that PAPi was more predictive of RVAD requirement
      when measured on inotropes (OR, 0.21; 95% CI, 0.02-0.97) than without (OR, 0.49;
      95% CI, 0.01-1.94). Furthermore, time from catheterization to LVAD did not
      significantly affect the predictive value of the PAPi (maximum time, 6 months).
      Receiver operating characteristic curve analysis revealed that optimal
      sensitivity and specificity were achieved using a PAPi threshold of 2.0.
      CONCLUSIONS: In LVAD recipients, the PAPi is an independent predictor of RVF and
      the need for RVAD support after LVAD implantation. This index appears more
      predictive in patients receiving inotropes and was not affected by time from
      catheterization to LVAD in our cohort.

PMID- 26212657
TI  - Voriconazole tolerability in lung transplant recipients: Is N-oxide metabolite
      responsible for phototoxicity?

PMID- 26212658
TI  - Early post-operative ventricular arrhythmias in patients with continuous-flow
      left ventricular assist devices.
AB  - BACKGROUND: Ventricular arrhythmias (VAs) are common in patients with a
      continuous-flow left ventricular assist device (CF-LVAD). The causes and clinical
      significance of early post-operative VAs have not previously been characterized
      in these patients. The purpose of this study was to assess the incidence,
      precipitants, and clinical impact of early VAs in patients supported by CF-LVADs.
      METHODS: Patients with a long-term CF-LVAD receiving care between January 1,
      2012, and March 1, 2014, were enrolled and followed prospectively. Implantable
      cardioverter-defibrillators (ICDs) were interrogated at baseline and throughout
      the follow-up period. VA was defined as ventricular tachycardia or ventricular
      fibrillation lasting >30 seconds or effectively terminated by appropriate ICD
      tachytherapy or external defibrillation. The primary end-point was the occurrence
      of early VAs (within 30 days of surgery). Secondary end-points were right
      ventricular (RV) failure and need for VA ablation. RESULTS: There were 162
      patients enrolled, and 38 (23.5%) experienced at least 1 early VA. Predictors of
      early VA were a history of pre-operative VAs, non-ischemic cardiomyopathy, and
      older age. Several conditions frequently encountered in the early post-operative
      period were identified as possible precipitants for VA episodes. Early VAs were
      associated with post-operative RV failure, particularly when patients received
      shocks instead of anti-tachycardia pacing. CONCLUSIONS: Early VAs are common and
      are associated with RV failure. ICD shocks, but not anti-tachycardia pacing, for
      early VAs are associated with acute worsening of RV failure.

PMID- 26212659
TI  - Impact of lung allocation score on survival in cystic fibrosis lung transplant
      recipients.
AB  - BACKGROUND: The lung allocation score (LAS) has changed organ allocation for lung
      transplantation in the United States. Previous investigations of transplant
      recipients reported an association between high LAS and an increased risk of
      death after lung transplantation. We hypothesize that a high LAS predicts
      survival in lung transplant recipients with cystic fibrosis (CF) in the United
      Network for Organ Sharing Scientific Registry of Transplant Recipients database.
      METHODS: A cohort study was conducted of 1,437 U.S. adult lung transplant
      recipients with CF from May 1, 2005, through December 31, 2012. The cohort was
      divided into a high-risk group and a low-risk group based on LAS. Survival data
      were examined using Kaplan-Meier estimates and Cox proportional hazard models to
      compare survival. The primary outcome was adjusted survival at 1 year after lung
      transplantation. RESULTS: The high-risk group of 318 patients with a median LAS
      of 69.6 (interquartile range 56.3-87.2) was compared with a low-risk group of
      1,119 patients with a median LAS of 38.8 (interquartile range 36.3-42.3).
      Patients in the high-risk group had a 41% increased relative risk of cumulative
      mortality at 1 year after transplantation compared with the low-risk group (16.1%
      vs 12.0%). After adjustment for known predictors of mortality, the risk of death
      at 1 year after transplantation remained elevated (hazard ratio = 1.41; 95%
      confidence interval = 1.00-2.01). The high-risk group had worse survival at 90
      days and 2 years after lung transplantation. CONCLUSIONS: High LAS are associated
      with worse survival in lung transplant recipients with CF.

PMID- 26212660
TI  - Low body mass index is associated with increased waitlist mortality among
      children listed for heart transplant.
AB  - BACKGROUND: In adults, low body mass index (BMI) and high BMI have been
      associated with increased mortality after heart transplantation. Studies of BMI
      in children with heart failure have had inconsistent results. METHODS: The United
      Network for Organ Sharing database has 4,035 listings for primary, isolated heart
      transplant in patients 3 to 18 years old (1995-2012). BMI percentile-for-age
      (BMI%) was calculated, and patients were stratified based on BMI% into 4 groups:
      underweight (BMI% <5, n = 701 [17.4%]), normal weight (BMI% 5-84, n = 2,321
      [57.5%]), overweight (BMI% 85-94, n = 440 [10.9%]), or obese (BMI% >=95, n = 573
      [14.2%]). Outcomes of patients on the waitlist and after transplantation were
      assessed. RESULTS: Unadjusted early waitlist mortality was highest in underweight
      patients (16.7%) compared with normal-weight (11.4%), overweight (10.9%), and
      obese (12.9%) patients (p = 0.04). In multivariable analysis, underweight
      patients had elevated risk-adjusted waitlist mortality (odds ratio = 1.4, 95%
      confidence interval = 1.0-2.2). Unadjusted post-transplant mortality did not
      differ across BMI% groups (underweight, 5.7%; normal weight, 5.4%; overweight,
      5.5%; obese, 5.8%), but obese patients had borderline higher risk-adjusted post
      transplant mortality (odds ratio = 1.7, 95% confidence interval = 1.0-3.0).
      Change in BMI% while waiting did not affect post-transplant mortality.
      CONCLUSIONS: Children listed for heart transplant are commonly either underweight
      or obese. Underweight patients have high risk-adjusted mortality before
      transplantation, whereas obese patients have borderline higher adjusted post
      transplant mortality.

PMID- 26212662
TI  - Boundary Caps Give Rise to Neurogenic Stem Cells and Terminal Glia in the Skin.
AB  - While neurogenic stem cells have been identified in rodent and human skin, their
      manipulation and further characterization are hampered by a lack of specific
      markers. Here, we perform genetic tracing of the progeny of boundary cap (BC)
      cells, a neural-crest-derived cell population localized at peripheral nerve
      entry/exit points. We show that BC derivatives migrate along peripheral nerves to
      reach the skin, where they give rise to terminal glia associated with dermal
      nerve endings. Dermal BC derivatives also include cells that self-renew in sphere
      culture and have broad in vitro differentiation potential. Upon transplantation
      into adult mouse dorsal root ganglia, skin BC derivatives efficiently
      differentiate into various types of mature sensory neurons. Together, this work
      establishes the embryonic origin, pathway of migration, and in vivo neurogenic
      potential of a major component of skin stem-like cells. It provides genetic tools
      to study and manipulate this population of high interest for medical
      applications.

PMID- 26212661
TI  - MicroRNA-153 Regulates the Acquisition of Gliogenic Competence by Neural Stem
      Cells.
AB  - Mammalian neural stem/progenitor cells (NSPCs) sequentially generate neurons and
      glia during CNS development. Here we identified miRNA-153 (miR-153) as a
      modulator of the temporal regulation of NSPC differentiation. Overexpression (OE)
      of miR-153 delayed the onset of astrogliogenesis and maintained NSPCs in an
      undifferentiated state in vitro and in the developing cortex. The transcription
      factors nuclear factor I (NFI) A and B, essential regulators of the initiation of
      gliogenesis, were found to be targets of miR-153. Inhibition of miR-153 in early
      neurogenic NSPCs induced precocious gliogenesis, whereas NFIA/B overexpression
      rescued the anti-gliogenic phenotypes induced by miR-153 OE. Our results indicate
      that miR-mediated fine control of NFIA/B expression is important in the molecular
      networks that regulate the acquisition of gliogenic competence by NSPCs in the
      developing CNS.

PMID- 26212663
TI  - Adherence to the food-based Japanese dietary guidelines in relation to metabolic
      risk factors in young Japanese women.
AB  - While Japanese diets have attracted considerable attention because of, for
      example, the long-life expectancy in Japan, their health benefits have not been
      examined. In the present study, we cross-sectionally examined whether adherence
      to the food-based Japanese dietary guidelines is associated with metabolic risk
      factors in 1083 Japanese women aged 18-22 years. Based on the Japanese Food Guide
      Spinning Top, adherence to the food-based Japanese dietary guidelines was
      assessed using dietary information on consumed servings of grain dishes,
      vegetable dishes, fish and meat dishes, milk and fruits and energy from snacks
      and alcoholic beverages during the preceding month, which was derived from a
      comprehensive diet history questionnaire. Higher dietary adherence was associated
      with higher intakes of protein, carbohydrate, dietary fibre, Na, K and vitamin C,
      and lower intakes of total and saturated fat. There was also an inverse
      association between dietary adherence and dietary energy density. After
      adjustment for potential confounding factors, dietary adherence was inversely
      associated with waist circumference (P for trend = 0.002). It also showed an
      inverse association with LDL-cholesterol concentrations (P for trend = 0.04).
      There was no association with the other metabolic risk factors examined,
      including BMI, systolic and diastolic blood pressure, total and HDL-cholesterol,
      TAG, glucose, glycated Hb and insulin concentrations. In conclusion, higher
      adherence to the food-based Japanese dietary guidelines, which was characterised
      by favourable dietary intakes of foods and nutrients as well as lower energy
      density, was associated with lower waist circumference and LDL-cholesterol
      concentrations in this group of young Japanese women.

PMID- 26212664
TI  - Blockade of dual-specificity phosphatase 28 decreases chemo-resistance and
      migration in human pancreatic cancer cells.
AB  - Pancreatic cancer remains one of the most deadly cancers, with a grave prognosis.
      Despite numerous endeavors to improve treatment of the neoplasm, limited progress
      has been made. In the present study, we investigated the role of dual specificity
      phosphatase 28 (DUSP28) in relation to anti-cancer drug sensitivity and migratory
      activity in human pancreatic cancer cells for the first time. Analysis using
      Universal exPress Codes (UPCs) with the GEO database showed significantly higher
      DUSP28 mRNA expression in pancreatic cancers. We found that DUSP28 was highly
      expressed in several human pancreatic cancer cell lines that showed resistance to
      anti-cancer drugs. Overexpression of DUSP28 decreased anti-cancer drug
      sensitivity and enhanced cellular migration via the ERK1/2 pathway in DUSP28
      negative cell lines. Knockdown of DUSP28 re-sensitized cells to anti-cancer drugs
      even at sublethal doses by inducing an apoptotic pathway and significantly
      reduced migration in DUSP28-positive human pancreatic cancer cell lines.
      Furthermore, DUSP28-positive cell line (Panc-1) xenograft models were more
      resistant to gemcitabine treatment than DUSP28-negative cell line (SNU-213)
      xenograft models. Collectively, these results indicate that DUSP28 plays a key
      role in drug resistance and migratory activity in human pancreatic cells, and
      suggest that targeting DUSP28 might have clinical relevance in eradicating
      malignant pancreatic cancers. 

PMID- 26212665
TI  - Self-Powered Triboelectric Nanosensor with Poly(tetrafluoroethylene) Nanoparticle
      Arrays for Dopamine Detection.
AB  - A self-powered triboelectric nanosensor (TENS) based on the contact-separation
      mode between a thin layer of poly(tetrafluoroethylene) (PTFE) with nanoparticle
      arrays and an aluminum film was fabricated for the detection of dopamine (DA) in
      the alkaline condition. High selectivity and sensitivity (detection limit of 0.5
      MUM, a linear range from 10 MUM to 1 mM) have been achieved through the strong
      interaction between the nonstick PTFE and DA via its oxidative self
      polymerization, and the output voltage and current of the developed TENS can
      reach 116 V and 33 MUA, which is exceptionally attractive for the fabrication of
      self-powered and portable device toward the detection of dopamine. 

PMID- 26212668
TI  - [Appropriateness of the use of incontinence absorbent products in hospitalized
      adults].
AB  - BACKGROUNDS: Improper use of incontinence absorbent products in adults can
      negatively affect self-esteem, quality of life and independence of the patient,
      as well as increase the workload and cause adverse events. There are few studies
      evaluating the appropriateness of diapers using validated scales for it, or the
      justification of nurses for its use in elderly who are hospitalized. OBJECTIVE:
      To determine the frequency of diaper use in patients admitted to a hospital and
      to identify the criteria that determined their use and adequacy. METHOD:
      Observational, cross-sectional study of adult patients using diapers while
      admitted in Inpatient Units. For data collection cut day was held in April 2013,
      collecting data from nursing assessment records, patients themselves and their
      family. Barthel Index items were used as criteria of adequacy concerning mobility
      and disposal. RESULTS: 228 patients admitted. 83 (34.4%) of them had diapers and
      25 (30.1%) of them had no criteria for using them. 28.8% (21) had not previously
      used diapers, the use of diapers in half of them was inappropriate. Factors
      associated with inappropriate use of diapers were older age, being female, more
      comorbidity and days of hospitalization. CONCLUSION: The results of this study
      show the often excessive use of incontinence absorbent products without proper
      application, not based on validated criteria.

PMID- 26212669
TI  - Manure biochar influence upon soil properties, phosphorus distribution and
      phosphatase activities: A microcosm incubation study.
AB  - Using manure-derived-biochar as an alternative phosphorus (P) source has bright
      future prospects to improve soil P status. A 98-day microcosm incubation
      experiment was set up for two soils which were amended with manure biochar at
      proportions of 0, 0.5% and 1.5%. Swine manure samples were air-dried and manure
      biochar was prepared by pyrolysis at 400  degrees C for 4 h. As determined by P
      31 nuclear magnetic resonance ((31)P NMR) spectroscopy, manure biochar mainly
      increased the contents and fractions of orthophosphate and pyrophosphate in two
      soils, while decreased those of monoesters (P<0.05). At the end of incubation,
      1.5% of manure biochar raised soil pH by 0.5 and 0.6 units, cation exchange
      capacity by 16.9% and 32.2%, and soil total P by 82.1% and 81.1% for silt loam
      and clay loam soils, respectively, as compared with those soils without biochar.
      Simultaneously, 1.5% of manure biochar decreased acid phosphomonoesterase
      activities by 18.6% and 34.0% for clay loam and silt loam, respectively; while it
      increased alkaline phosphomonoesterase activities by 28.5% and 95.1% for clay
      loam and silt loam, respectively. The enhancement of soil P availability after
      manure biochar addition was firstly due to the orthophosphate and pyrophosphate
      as the major P species in manure biochar which directly increased contents of
      soil inorganic P, and also attributed to the decomposition of some organic P like
      monoesters by enhanced alkaline phosphomonoesterase activities from manure
      biochar addition.

PMID- 26212670
TI  - The Japan Flavour and Fragrance Materials Association's (JFFMA) safety assessment
      of acetal food flavouring substances uniquely used in Japan.
AB  - Using the procedure devised by the Joint FAO/WHO Expert Committee on Food
      Additives (JECFA), we performed safety evaluations on five acetal flavouring
      substances uniquely used in Japan: acetaldehyde 2,3-butanediol acetal, acetoin
      dimethyl acetal, hexanal dibutyl acetal, hexanal glyceryl acetal and 4-methyl-2
      pentanone propyleneglycol acetal. As no genotoxicity study data were available in
      the literature, all five substances had no chemical structural alerts predicting
      genotoxicity. Using Cramer's classification, acetoin dimethyl acetal and hexanal
      dibutyl acetal were categorised as class I, and acetaldehyde 2,3-butanediol
      acetal, hexanal glyceryl acetal and 4-methyl-2-pentanone propyleneglycol acetal
      as class III. The estimated daily intakes for all five substances were within the
      range of 1.45-6.53 ug/person/day using the method of maximised survey-derived
      intake based on the annual production data in Japan from 2001, 2005, 2008 and
      2010, and 156-720 ug/person/day using the single-portion exposure technique
      (SPET), based on the average use levels in standard portion sizes of flavoured
      foods. The daily intakes of the two class I substances were below the threshold
      of toxicological concern (TTC) - 1800 MUg/person/day. The daily intakes of the
      three class III substances exceeded the TTC (90 MUg/person/day). Two of these,
      acetaldehyde 2,3-butanediol acetal and hexanal glyceryl acetal, were expected to
      be metabolised into endogenous products after ingestion. For 4-methyl-2-pentanone
      propyleneglycol acetal, one of its metabolites was not expected to be metabolised
      into endogenous products. However, its daily intake level, based on the estimated
      intake calculated by the SPET method, was about 1/15 000th of the no observed
      effect level. It was thus concluded that all five substances raised no safety
      concerns when used for flavouring foods at the currently estimated intake levels.
      While no information on in vitro and in vivo toxicity for all five substances was
      available, their metabolites were judged as raising no safety concerns at the
      current levels of intake.

PMID- 26212671
TI  - The impact of resonance stabilization on the intramolecular hydrogen-atom shift
      reactions of hydrocarbon radicals.
AB  - A series of intramolecular H-atom shift reactions of both alkenyl and allylic
      radicals were investigated by using CBS-QB3 electronic structure calculations. In
      the first set of reactions, an alkyl radical site was converted into an allylic
      radical site. In the second set, an allylic radical was converted into another
      allylic radical. The results are discussed in the context of a Benson-type model
      to examine the impact of the transition-state partial resonance stabilization on
      both the activation energies and the pre-exponential factors. In most cases, the
      differences in the activation energies relative to those for the analogous alkyl
      radicals are primarily due to the barriers of the bimolecular reaction component
      of the activation energy. For the first set of reactions, there is additional
      entropy loss relative to the alkyl radical analogues. This additional loss of
      entropy may be smaller than some previous estimates. The pre-exponential factors
      for the second set of reactions are generally similar to those of the analogous
      alkyl radical reactions (once the double bond in the transition state is
      accounted for). 

PMID- 26212672
TI  - A prospective trial comparing isotonic with hypotonic maintenance fluids for
      prevention of hospital-acquired hyponatraemia.
AB  - BACKGROUND: Recent literature suggests that hypotonic fluids increase the risk of
      hospital-acquired hyponatraemia; despite this, hypotonic fluids are widely used.
      OBJECTIVES: To compare the change in serum sodium following the use of hypotonic
      (0.3% saline, 0.45% saline) or isotonic (0.9% saline) intravenous (IV)
      maintenance solutions in hospitalised children. STUDY DESIGN: This was a
      randomised controlled trial. Children aged 3 months to 15 years with medical or
      surgical disorders were randomised to receive one of three maintenance IV fluids:
      two hypotonic solutions (3.3% dextrose in 0.3% saline or 5% dextrose in 0.45%
      saline) and one isotonic solution (5% dextrose in 0.9% saline). The primary
      outcome was serum sodium levels at 8 hours. Secondary outcomes included the
      incidence of hospital-acquired hyponatraemia, adverse events attributable to IV
      solutions and length of hospital stay. RESULTS: 151 children were assigned
      randomly to receive 0.3% saline (n = 49), 0.45% saline (n = 50) or 0.9% saline (n
      = 52). Baseline characteristics were similar for the three groups. At 8 hours,
      mean (SD) serum sodium was lower in the hypotonic solutions groups [0.3% saline
      134.65 (1.9) mmol/L, 0.45% saline 134.90 (2.3) mmol/L than 0.9% saline 137.98
      (2.8) mmol/L] (P < 0.0001). The incidence of hospital-acquired hyponatraemia was
      higher in the hypotonic groups [0.3% saline 10/49 (20.4%), 0.45% saline 11/50
      (22%) than 0.9% saline 1/52 (1.9%), P = 0.006). There were no differences in
      other adverse effects or length of hospital stay between the groups. CONCLUSION:
      Hypotonic IV solutions increase the incidence of hospital-acquired hyponatraemia.
      Isotonic solutions are a safer alternative.

PMID- 26212673
TI  - Physical Activity Patterns Among Older Adults With and Without Knee
      Osteoarthritis in Six European Countries.
AB  - OBJECTIVE: To investigate patterns of physical activity in older adults with knee
      osteoarthritis (OA) compared to older adults without knee OA across 6 European
      countries. We expect country-specific differences in the physical activity levels
      between persons with knee OA compared to persons without knee OA. A varying
      degree of physical activity levels across countries would express a facilitating
      or impeding influence of the social, environmental, and other contextual factors
      on a physically active lifestyle. METHODS: Baseline cross-sectional data from the
      European Project on Osteoarthritis were analyzed. In total, 2,551 participants
      from 6 European countries (Germany, Italy, The Netherlands, Spain, Sweden, and
      the UK) were included. RESULTS: Participants with knee OA were less likely to
      follow physical activity recommendations and had poorer overall physical activity
      profiles than those without knee OA (mean 62.9 versus 81.5 minutes/day,
      respectively; P = 0.015). The magnitude of this difference varied across
      countries. Detailed analysis showed that low physical activity levels in persons
      with knee OA could be attributed to less everyday walking time (odds ratio 1.31,
      95% confidence interval 1.07-1.62). CONCLUSION: This study highlighted the fact
      that having knee OA is associated with a varying degree of physical activity
      patterns in different countries. This national variation implies that low levels
      of physical activity among persons with knee OA cannot be explained exclusively
      by individual or disease-specific factors, but that social, environmental, and
      other contextual factors should also be taken into account.

PMID- 26212674
TI  - Hb G-Waimanalo [A1] or alpha64(E13)Asp->Asn (alpha1) (HBA1: c.193G>A) Observed in
      a Bulgarian Family.
AB  - The abnormal hemoglobin (Hb) with an aspartic acid to asparagine substitution at
      alpha64 has been found on both the alpha2- and alpha1-globin genes. It has been
      described in many different populations under different names, but never in
      Bulgaria. Using the recently proposed nomenclature, Hb G-Waimanalo [A1] refers to
      the HBA1: c.193G > A, while Hb G-Waimanalo [A2] refers to the HBA2: c.193G > A
      mutation. Here, we present the first family from Bulgaria with Hb G-Waimanalo
      [A1]. 

PMID- 26212675
TI  - Prevalence of Depression in Patients with beta-Thalassemia as Assessed by the
      Beck's Depression Inventory [Hemoglobin. 2014;38(4):289-291].

PMID- 26212676
TI  - Prevention of Hb Bart's (gamma4) Disease Associated with the - -(THAI) alpha(0)
      Thalassemia Deletion in Mainland China.
AB  - alpha-Thalassemia (alpha-thal) is a common inherited disease in southern China.
      The severest form is Hb Bart's (gamma4) disease, in which the affected fetuses
      almost always die in utero or shortly after birth, and the mothers are at high
      risk for severe morbidity. The most common type of alpha(0)-thalassemia (alpha(0)
      thal) in southern China is Southeast Asian (- -(SEA)) deletion. Occasionally, Hb
      Bart's disease, caused by a compound heterozygosity for the - -(SEA) and - 
      (THAI) alpha(0)-thal deletions, can also be encountered. In this study, we report
      our experience with the prevention of Hb Bart's disease associated with the - 
      (THAI) alpha(0)-thal deletion. A total of 385 couples at risk for Hb Bart's
      disease, including seven who tested positive for the - -(SEA) deletion in one
      partner and the - -(THAI) deletion in the other, were found. Different prenatal
      procedures were offered, depending on the gestational age at presentation. Sixty
      six affected fetuses were diagnosed prenatally; among these, two cases of Hb
      Bart's disease were compound heterozygotes for the - -(SEA) and - -(THAI)
      deletions. All affected pregnancies were terminated in time. We also presented a
      diagnostic protocol for identification of alpha(0)-thal trait that can reduce the
      number of samples for detection of the - -(THAI) deletion. 

PMID- 26212677
TI  - Dehydrogenative TEMPO-Mediated Formation of Unstable Nitrones: Easy Access to N
      Carbamoyl Isoxazolines.
AB  - N-carbamoyl nitrones represent an important class of reagents for the synthesis
      of a variety of natural and biologically active compounds. These compounds are
      generally converted into valuable 4-isoxazolines upon cyclization reaction with
      dipolarophiles. However, these types of N-protected nitrones are highly unstable,
      which limits their synthesis, storage and practical use, enforcing alternative
      lengthy or elaborated synthetic routes. In this work, a 2,2,6,6
      tetramethylpiperidin-1-oxyl (TEMPO)-mediated formal "dehydrogenation" of N
      protected benzyl-, allyl- and alkyl-substituted hydroxylamines followed by in
      situ trapping of the generated unstable nitrones into N-carbamoyl 4-isoxazolines
      is presented. A plausible mechanism is also proposed, in which the dipolarophile
      shows an important assistant role in the generation of the active nitrone
      intermediate. This simple protocol avoids the problematic isolation of N
      carbamoyl protected nitrones, providing new synthetic possibilities in
      isoxazoline chemistry. 

PMID- 26212678
TI  - Membrane bioreactor: A mini review on recent R&D works.
AB  - Membrane bioreactor (MBR) has been widely applied worldwide in full scale. Recent
      research and development trends of MBR technology has been shifted from process
      optimization and economic evaluation to installation of new process architecture
      to enrich functional strains like nitrifiers or providing assisted field for
      performance enhancement, to incorporation of affordable adsorbents or scouring
      agent for membrane fouling mitigation, and to applying MBR hybrid systems for
      achieving simultaneous removals of nutrients and other pollutants. This mini
      review summarized the recent works, principally in 2014-2015, on the above
      aspects, and provided a discussion on the osmotic MBR based on forward osmosis on
      its use of high-osmotic-pressure draw solution and the pre-treatment needed, and
      the reverse solute leakage that affects the MBR efficiency. 

PMID- 26212679
TI  - Bioelectricity production from microbial fuel cell using mixed bacterial culture
      isolated from distillery wastewater.
AB  - The effect of various system parameters such as wastewater Chemical Oxygen Demand
      (COD) concentration, pH, conductivity, membrane size and thickness on efficient
      energy production using mixed isolated culture from the distillery wastewater in
      the MFC was studied. The power density increased with increase in the anolyte pH
      from 6 to 8. The peak power density and COD removal efficiency was observed as
      63.8+/-0.65 mW/m(2) and 63.5+/-1.5% at pH 8, respectively. The MFC performance
      increased with increasing COD concentration (800-3200 mg/l), conductivity (1.1
      9.7 mS/cm) and membrane area (8-24 cm(2)). The MFC operating with wastewater COD
      concentration of 3200 mg/l and its conductivity of 9.7 mS/cm produced the highest
      power density of 202+/-6 mW/m(2) with a corresponding current density of 412+/-12
      mA/m(2). The results showed that the efficient electricity generation and
      simultaneous treatment of distillery wastewater can be attained in the MFC.

PMID- 26212680
TI  - Carbonic anhydrase VI: a novel marker for salivary serous acinar differentiation
      and its application to discriminate acinic cell carcinoma from mammary analogue
      secretory carcinoma of the salivary gland.
AB  - AIMS: Carbonic anhydrase VI (CA6) is present in serous acinar cells of human
      salivary glands. The aim of this study was to investigate the diagnostic utility
      of CA6 in differentiating acinic cell carcinoma (AciCC) from its morphological
      mimic mammary analogue secretory carcinoma (MASC) of the salivary gland. METHODS
      AND RESULTS: CA6 immunostaining was performed in 28 cases of AciCC and 14 cases
      of MASC. All cases of AciCC showed positive CA6 staining. The staining pattern
      correlated with the number of serous acinar cells in tumours. All MASCs stained
      negatively for CA6. The results were compared with those obtained with currently
      used markers, including DOG1, mammaglobin, S100, and vimentin. CA6 showed
      sensitivity and specificity as high as those of DOG1 in diagnosing AciCC. CA6
      expression was focally observed in basal cell adenoma and in one case of
      cystadenocarcinoma (1/3), but not in other salivary gland tumours, including
      mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary duct carcinoma,
      lymphoepithelial carcinoma, epithelial-myoepithelial carcinoma, and pleomorphic
      adenoma. CONCLUSIONS: CA6 is a specific marker for serous acinar cells of
      salivary glands and AciCC. CA6 has sensitivity and specificity equal to those of
      DOG1 in the differential diagnosis between AciCC and MASC. A combination of CA6
      and DOG1 could be an ideal immunohistochemical panel for AciCC.

PMID- 26212681
TI  - Endocytoscopic observation of duodenal polyps associated with familial
      adenomatous polyposis: Report of four cases.

PMID- 26212682
TI  - Suicidal Fatality from Azide Ingestion.
AB  - A 35-year-old man ingested an unknown amount of sodium azide and died within 2 h.
      The postmortem interval was 3 days. No alcohol or drugs were found in the blood
      and urine. Azide was derivatized in the peripheral blood, urine, and vitreous
      fluid with propionic anhydride. A portion of the headspace was injected onto a
      gas chromatograph with a nitrogen-phosphorus detector. Azide was quantitated in
      the peripheral blood (1.1 MUg/mL), urine (7.5 MUg/mL), and vitreous (43 MUg/mL).
      The vitreous appears to be a better fluid for azide screening because of slower
      degradation.

PMID- 26212683
TI  - Lymph node metastasis in clinical stage IA peripheral lung cancer.
AB  - OBJECTIVES: To investigate lymph node metastasis especially the intrapulmonary
      node in clinical IA peripheral lung cancer patients to evaluate the indications
      for lung segmentectomy in lymph node level. MATERIALS AND METHODS: Patients
      (n=292) with clinical stage IA peripheral lung cancer received radical lobectomy
      at our department between October 2013 and July 2014 were enrolled in our study.
      Lymph nodes were obtained during routine surgical procedures while segmental
      lymph nodes were dissected from the resected lobe for pathological examination.
      New classification for pulmonary adenocarcinoma with each histologic component
      was also analyzed. RESULTS: The percentage of patients found to have no lymph
      node metastasis was 90.4% (264/292). Tumor size on computed tomography and tumor
      consistency were independent predictors for lymph node metastasis. Tumor with a
      dominant ground-glass opacity (GGO) component was a good predictor for lymph node
      metastasis (p<0.001). Metastasis was more common in larger tumors (p<0.001), but
      there was non-tumor bearing segment metastasis even in tumor less than 1cm.
      Patients with micropapillary or solid component were correlated with lymph node
      metastasis (p=0.001 and p=0.009, respectively). CONCLUSIONS: The rate of
      metastasis to the lymph nodes is very low in clinical stage IA peripheral lung
      cancer patients. Patients with a dominant GGO component on CT might be the
      suitable candidates for lung segmentectomy because of almost no lymph node
      metastasis. Careful selection should be made for the patients with tumor size <=2
      cm who had metastasized nodes in non-tumor bearing segment when considering
      segmentectomy. If the resected tumor had micropapillary or solid component, the
      lobectomy might be considered.

PMID- 26212684
TI  - Developmental and behavioral consequences of prenatal methamphetamine exposure: A
      review of the Infant Development, Environment, and Lifestyle (IDEAL) study.
AB  - This study reviews the findings from the Infant Development, Environment, and
      Lifestyle (IDEAL) study, a multisite, longitudinal, prospective study designed to
      determine maternal outcome and child growth and developmental findings following
      prenatal methamphetamine exposure from birth up to age 7.5 years. These findings
      are presented in the context of the home environment and caregiver
      characteristics to determine how the drug and the environment interact to affect
      the outcome of these children. No neonatal abstinence syndrome requiring
      pharmacologic intervention was observed but heavy drug exposure was associated
      with increased stress responses in the neonatal period. Poorer inhibitory control
      was also observed in heavy methamphetamine exposed children placing them at high
      risk for impaired executive function. Independent of methamphetamine exposure,
      children with more responsive home environments to developmental and emotional
      needs demonstrated lower risks for internalizing and externalizing behavior.

PMID- 26212685
TI  - Potent immunotherapy against well-established thymoma using adoptively
      transferred transgene IL-6-engineered dendritic cell-stimulated CD8+ T-cells with
      prolonged survival and enhanced cytotoxicity.
AB  - BACKGROUND: Adoptive transfer of CD8(+) T-cells specific for tumor-antigens is an
      attractive strategy for anti-tumor therapy. In the present study, the subsets TA
      and TB were used to represent the population of CD8(+) T cells generated by
      culturing the respective cells with irradiated dendritic cells (DCs) pulsed with
      ovalbumin (OVA) protein and transfected with adenoviral vector constructs as
      described. METHODS: Naive OVA specific CD8(+) T cells were isolated from the
      spleen of OVA-specific T-cell receptor transgenic OTI mice. The subsets TA and TB
      were then generated by in vitro activating the population of CD8(+) T cells with
      OVA-pulsed DCs transfected with IL-6-expressing adenoviral vector (AdVIL-6 ) or
      the control vector (AdVNull ). To assess their in vivo immunotherapeutic effects,
      TA - or TB -cells were intravenously transferred into C57BL/6 mice bearing EG7
      thymoma (6-8 mm in diameter). RESULTS: TA -cells displayed a higher level of
      expression of CD62 l, IL-7R, FasL, perforin and CCR6, and also exhibited more
      potent in vitro cytotoxicity to OVA-expressing EG7 thymoma cells via perforin-
      and Fas/FasL-mediated apoptosis than TB -cells. CD8(+) T-cell survival was
      kinetically analyzed in C57BL/6 mice transferred with TA - or TB -cells by flow
      cytometry. We found that the adoptively transferred TA -cells had prolonged
      survival and enhanced T-cell memory development compared to TB -cells. In
      addition, TA -, but not TB -cells were able to eradicate well-established EG7
      thymomas in all eight tumor-bearing mice. CONCLUSIONS: Our data suggest that
      AdVIL-6 -transfected DC-stimulated CD8(+) T cells with potent cytotoxicity and
      survival advantage may serve as an effective adoptive CD8(+) T-cell immunotherapy
      strategy for anti-tumor treatment.

PMID- 26212687
TI  - Clinical risk factors for ovarian torsion.
AB  - Ovarian torsion is a relatively common gynaecological emergency, usually
      presenting as acute lower abdominal pain. The underlying pathophysiology involves
      torsion of the ovarian tissue on its pedicle leading to reduced venous return,
      stromal oedema, internal haemorrhage and infarction with the subsequent sequelae.
      It is not clear from looking at the literature which factors are responsible for
      the development of ovarian torsion and what are the odds of a particular clinical
      feature in determining the likelihood of developing ovarian torsion. In order to
      assess the likelihood of a particular clinical feature to be a risk factor for
      ovarian torsion, we studied the prevalence of each presenting clinical feature in
      the background population of women, for instance, looking at ovarian cysts and
      compared this with the odds of the feature occurring in the affected population
      of torsion patients. Thus we compared the odds of various clinical variables in
      ovarian torsion patients against the odds of the same feature occurring in the
      background population of women. Ovarian cysts are three times more common in
      ovarian torsion cohorts than in the general population. Evidence suggests that
      ovarian cysts are very common in the asymptomatic pregnant cohorts; however, they
      spontaneously resolve as the pregnancy progresses. Pregnancy is a risk factor for
      torsion (odds ratio: 18:1); however, it remains an uncommon event (0.167%). Tubal
      sterilisation practices vary according to geographical location and over
      chronology of the published literature. After considering the extremes of
      variation in tubal sterilisation practices, the risk of torsion increases by at
      least 8-fold following surgery. Hysterectomy with ovarian conservation is not a
      risk factor of torsion. 

PMID- 26212686
TI  - Multimodal communication in chimpanzees.
AB  - A fundamental characteristic of human language is multimodality. In other words,
      humans use multiple signaling channels concurrently when communicating with one
      another. For example, people frequently produce manual gestures while speaking,
      and the words a person perceives are impacted by visual information. For this
      study, we hypothesized that similar to the way that humans regularly couple their
      spoken utterances with gestures and facial expressions, chimpanzees regularly
      produce vocalizations in conjunction with other communicative signals. To test
      this hypothesis, data were collected from 101 captive chimpanzees living in mixed
      sex social groupings of seven to twelve individuals. A total of 2,869 vocal
      events were collected. The data indicate that approximately 50% of the vocal
      events were produced in conjunction with another communicative modality. In
      addition, approximately 68% were directed to a specific individual, and these
      directed vocalizations were more likely to include a signal from another
      communicative modality than were vocalizations that were not directed to a
      specific individual. These results suggest that, like humans, chimpanzees often
      pair their vocalizations with signals from other communicative modalities. In
      addition, chimpanzees appear to use their communicative signals strategically to
      meet specific socio-communicative ends, providing support for the growing
      literature that indicates that at least some chimpanzee vocal signaling is
      intentional.

PMID- 26212688
TI  - Understanding the cryotolerance of lactic acid bacteria using combined
      synchrotron infrared and fluorescence microscopies.
AB  - Freezing is widely used for preserving different types of cells. Frozen
      concentrates of lactic acid bacteria (LAB) are extensively used for manufacturing
      food, probiotic products and for green chemistry and medical applications.
      However, the freezing and thawing processes cause cell injuries that result in
      significant cell death. Producing homogeneous bacterial populations with high
      cryotolerance remains a real challenge. Our objective was to investigate the
      biochemical and physiological changes in a LAB model at the cell scale following
      fermentation and freezing in order to identify cellular biomarkers of
      cryotolerance. Infrared spectra of individual bacteria produced by applying
      different fermentation and freezing conditions were acquired using synchrotron
      radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to achieve
      sub-cellular spatial resolution. Fluorescent microscopy was concomitantly
      assessed, thus making possible to simultaneously analyse the biochemistry and
      physiological state of a single cell for the first time. Principal component
      analysis was used to evaluate changes in cell composition, with particular focus
      on lipids, proteins and polysaccharides. SR-FTIR results indicated that before
      freezing, freeze-resistant cells grown in a rich medium presented a high content
      of CH3 groups from lipid chains, of cell proteins in an alpha-helix secondary
      structure and of charged polymers such as teichoic and lipoteichoic acids that
      constitute the Gram-positive bacterial wall. Moreover, SR-FTIR microspectroscopy
      made it possible to reveal cell heterogeneity within the cluster of resistant
      cells, which was ascribed to the diversity of potential substrates in the growth
      medium. Freezing and thawing processes induced losses of membrane integrity and
      cell viability in more than 90% of the freeze-sensitive bacterial population.
      These damages leading to cell death were ascribed to biochemical modification of
      cell membrane phospholipids, in particular a rigidification of the cytoplasmic
      membrane following freezing. Furthermore the freeze-resistant cells remained
      viable after freezing and thawing but a modification of protein secondary
      structure was detected by SR-FTIR analysis. These results highlighted the
      potential application of bimodal analysis by SR-FTIR and fluorescence microscopy
      to increase our knowledge about mechanisms related to cell damage. 

PMID- 26212689
TI  - Precise Design of Phosphorescent Molecular Butterflies with Tunable Photoinduced
      Structural Change and Dual Emission.
AB  - Photoinduced structural change (PSC) is a fundamental excited-state dynamic
      process in chemical and biological systems. However, precise control of PSC
      processes is very challenging, owing to the lack of guidelines for designing
      excited-state potential energy surfaces (PESs). A series of rationally designed
      butterfly-like phosphorescent binuclear platinum complexes that undergo
      controlled PSC by Pt-Pt distance shortening and exhibit tunable dual (greenish
      blue and red) emission are herein reported. Based on the Bell-Evans-Polanyi
      principle, it is demonstrated how the energy barrier of the PSC, which can be
      described as a chemical-reaction-like process between the two energy minima on
      the first triplet excited-state PES, can be controlled by synthetic means. These
      results reveal a simple method to engineer the dual emission of molecular systems
      by manipulating PES to control PSC. 

PMID- 26212690
TI  - Field populations of native Indian honey bees from pesticide intensive
      agricultural landscape show signs of impaired olfaction.
AB  - Little information is available regarding the adverse effects of pesticides on
      natural honey bee populations. This study highlights the detrimental effects of
      pesticides on honey bee olfaction through behavioural studies, scanning electron
      microscopic imaging of antennal sensillae and confocal microscopic studies of
      honey bee brains for calcium ions on Apis cerana, a native Indian honey bee
      species. There was a significant decrease in proboscis extension response and
      biologically active free calcium ions and adverse changes in antennal sensillae
      in pesticide exposed field honey bee populations compared to morphometrically
      similar honey bees sampled from low/no pesticide sites. Controlled laboratory
      experiments corroborated these findings. This study reports for the first time
      the changes in antennal sensillae, expression of Calpain 1(an important calcium
      binding protein) and resting state free calcium in brains of honey bees exposed
      to pesticide stress. 

PMID- 26212691
TI  - Training of Affect Recognition impacts electrophysiological correlates of facial
      affect recognition in schizophrenia: Analyses of fixation-locked potentials.
AB  - OBJECTIVES: Training of Affect Recognition (TAR) is a useful approach to
      restoring cognitive function in schizophrenic patients. Along with improving
      visual exploration of faces and altering central information processing in
      relevant brain areas, TAR attenuates impairments in facial affect recognition. In
      the present study, we investigate the effects of TAR on early
      electrophysiological correlates of facial affect recognition in schizophrenia.
      METHODS: The study population comprised 12 schizophrenic patients and 14 healthy
      controls. In each individual, we carried out EEG, concomitant measurements of
      scanning eye movements and fixation-based low resolution electromagnetic
      tomography (sLORETA) analyses of brain electric activity. All analyses were
      performed at baseline and after participation in TAR. RESULTS: In patients, brain
      activation patterns significantly changed after completing the TAR. Functional
      improvements were particularly pronounced in the superior parietal and inferior
      parietal lobes, where trained patients showed a larger increase in activation
      than untrained healthy controls. CONCLUSIONS: The TAR activates compensatory
      brain processes involved in the perception, attention and evaluation of emotional
      stimuli. This may underlie the established behavioral effects of the TAR in
      schizophrenic patients, which include improvements in facial affect recognition
      and alterations of visual exploration strategies.

PMID- 26212692
TI  - Silver-Catalyzed Cross-Coupling of Isocyanides and Active Methylene Compounds by
      a Radical Process.
AB  - Isocyanides are versatile building blocks, and have been extensively exploited in
      C-H functionalization reactions. However, transition-metal-catalyzed direct C-H
      functionalization reactions with isocyanides suffer from over-insertion of
      isocyanides. Reported herein is a radical coupling/isomerization strategy for the
      cross-coupling of isocyanides with active methylene compounds through silver
      catalysis. The method solves the over-insertion issue and affords a variety of
      otherwise difficult to synthesize beta-aminoenones and tricarbonylmethanes under
      base- and ligand-free conditions. This report presents a new fundamental C-C bond
      forming reaction of two basic chemicals.

PMID- 26212693
TI  - Comparison of calcium alginate and carboxymethyl cellulose for nasal packing
      after endoscopic sinus surgery: a prospective, randomised, controlled single
      blinded trial.
AB  - OBJECTIVES: Calcium alginate is a biodegradable gel-transforming agent widely
      used for nasal packing. It can reduce pain and improve comfort. However, few
      randomised controlled trials have compared the efficacy of calcium alginate nasal
      packing with that of other biodegradable gel-transforming materials. DESIGN:
      Prospective, randomised, single-blinded controlled study. SETTING: Yonsei
      University Severance Hospital, a tertiary academic medical centre. PARTICIPANTS:
      Twenty-seven patients (54 nostrils) with chronic rhinosinusitis who were
      scheduled for bilateral endoscopic sinus surgery were enrolled. After surgery,
      one nostril was packed with calcium alginate and the other with carboxymethyl
      cellulose. Only patients with an intersinus chronic rhinosinusitis severity score
      difference of <=1 were included. MAIN OUTCOME MEASURES: Visual analogue scale
      (VAS) scores for postoperative pain, discomfort from nasal discharge and pain
      during packing removal were analysed. Two independent rhinologists who were
      blinded to the assessments separately scored adhesions, oedema and infection by
      endoscopic digital photography at 1, 4 and 8 weeks postoperatively. RESULTS:
      There were no significant differences in VAS scores for postoperative pain,
      discomfort from nasal discharge or pain during packing removal between calcium
      alginate packings and carboxymethyl cellulose packings. Inter-rater variability
      of adhesion, oedema and infection scores was acceptable. Adhesion severity and
      oedema scores at 4 weeks were significantly lower with calcium alginate packing
      than with carboxymethyl cellulose. Infection severity scores also tended to be
      lower with calcium alginate than with carboxymethyl cellulose, but the difference
      was not significant. CONCLUSIONS: Calcium alginate nasal packing is associated
      with reduced severity of oedema and adhesions after endoscopic sinus surgery.

PMID- 26212694
TI  - Innate immune response and implant loosening: Interferon gamma is inversely
      associated with early migration of total knee prostheses.
AB  - To allow prediction of the risk of loosening prior to surgery, we investigated
      the relationship between innate immune cytokine response via TLR2 stimulation and
      early migration of six different knee prostheses using RSA (radiostereometry).
      This study included 114 patients of a prospective RSA-cohort who received a total
      knee arthroplasty. Whole blood cytokine responses were obtained by ex vivo
      stimulation with tripalmitoyl-S-glycerylcysteine (Pam3Cys-SK4) for assessment of
      the TLR2 immune response. Early migration was calculated using the maximum total
      point motion (MTPM) 1 year post surgery. Principal component analysis (PCA) was
      applied to the cytokine data to reduce the correlated data of individual
      cytokines and identified two components. Subsequently, linear mixed model
      analyses were applied with adjustments for gender, age, BMI, time-to-blood
      sampling, and prosthesis type. Component 1, consisting of IFNgamma, IL-12p40, IL
      10, IL-1beta, TNFalpha, and IL-6, showed a significant inverse association (beta
      = -0.128; p = 0.041) with MTPM. Further analysis showed that IFNgamma (beta = 
      0.161, p = 0.008) had the highest contribution to this association and is
      particularly found in patients receiving another prosthesis than Nexgen (beta = 
      0.239; p < 0.001). In conclusion, patients with high levels of IFNgamma upon
      stimulation of TLR2 are at lower risk of early migration of their knee
      prosthesis.

PMID- 26212695
TI  - Lower LINE-1 methylation in first-episode schizophrenia patients with the history
      of childhood trauma.
AB  - AIM: We investigated methylation of DNA repetitive sequences (LINE-1 and BAGE) in
      peripheral blood leukocytes from first-episode schizophrenia (FES) patients and
      healthy controls (HCs) with respect to childhood adversities. MATERIALS &
      METHODS: Patients were divided into two subgroups based on the history of
      childhood trauma - FES(+) and FES(-) subjects. The majority of HCs had a negative
      history of childhood trauma - HCs(-) subjects. RESULTS: FES(+) patients had
      significantly lower LINE-1 methylation in comparison with FES(-) patients or HC(
      ) subjects. Emotional abuse and total trauma score predicted lower LINE-1
      methylation in FES patients, while general trauma score was associated with lower
      BAGE methylation in HCs. CONCLUSION: Childhood adversities might be associated
      with global DNA hypomethylation in adult FES patients.

PMID- 26212696
TI  - A global RNA-seq-driven analysis of CHO host and production cell lines reveals
      distinct differential expression patterns of genes contributing to recombinant
      antibody glycosylation.
AB  - Boehringer Ingelheim uses two CHO-DG44 lines for manufacturing biotherapeutics,
      BI-HEX-1 and BI-HEX-2, which produce distinct cell type-specific antibody
      glycosylation patterns. A recently established CHO-K1 descended host, BI-HEX-K1,
      generates antibodies with glycosylation profiles differing from CHO-DG44.
      Manufacturing process development is significantly influenced by these unique
      profiles. To investigate the underlying glycosylation related gene expression, we
      leveraged our CHO host and production cell RNA-seqtranscriptomics and product
      quality database together with the CHO-K1 genome. We observed that each BI-HEX
      host and antibody producing cell line has a unique gene expression fingerprint.
      CHO-DG44 cells only transcribe Fut10, Gfpt2 and ST8Sia6 when expressing
      antibodies. BI-HEX-K1 cells express ST8Sia6 at host cell level. We detected a
      link between BI-HEX-1/BI-HEX-2 antibody galactosylation and mannosylation and the
      gene expression of the B4galt gene family and genes controlling mannose
      processing. Furthermore, we found major differences between the CHO-DG44 and CHO
      K1 lineages in the expression of sialyl transferases and enzymes synthesizing
      sialic acid precursors, providing a rationale for the lack of immunogenic
      NeuGc/NGNA synthesis in CHO. Our study highlights the value of systems
      biotechnology to understand glycoprotein synthesis and product glycoprofiles.
      Such data improve future production clone selection and process development
      strategies for better steering of biotherapeutic product quality. 

PMID- 26212697
TI  - Viral vaccines and their manufacturing cell substrates: New trends and designs in
      modern vaccinology.
AB  - Vaccination is one of the most effective interventions in global health. The
      worldwide vaccination programs significantly reduced the number of deaths caused
      by infectious agents. A successful example was the eradication of smallpox in
      1979 after two centuries of vaccination campaigns. Since the first variolation
      administrations until today, the knowledge on immunology has increased
      substantially. This knowledge combined with the introduction of cell culture and
      DNA recombinant technologies revolutionized vaccine design. This review will
      focus on vaccines against human viral pathogens, recent developments on vaccine
      design and cell substrates used for their manufacture. While the production of
      attenuated and inactivated vaccines requires the use of the respective
      permissible cell substrates, the production of recombinant antigens, virus-like
      particles, vectored vaccines and chimeric vaccines requires the use - and often
      the development - of specific cell lines. Indeed, the development of novel modern
      viral vaccine designs combined with, the stringent safety requirements for
      manufacture, and the better understanding on animal cell metabolism and
      physiology are increasing the awareness on the importance of cell line
      development and engineering areas. A new era of modern vaccinology is arriving,
      offering an extensive toolbox to materialize novel and creative ideas in vaccine
      design and its manufacture. 

PMID- 26212698
TI  - Serum parathyroid hormone and active vitamin D in chronic periodontitis.
AB  - OBJECTIVES: To study the association between periodontitis and serum parathyroid
      hormone (PTH) and the response of PTH to periodontal therapy in type 1 diabetic
      patients (T1DM). We also investigated the PTH-1,25(OH)2 D axis in the T1DM group.
      METHODS: Periodontal health status was recorded in 54 periodontitis patients and
      30 periodontally healthy controls (case-control data). Data were also collected
      from patients with type 1 diabetes mellitus at the baseline (n = 76) and after
      periodontal therapy (intervention data) (n = 53). RESULTS: Periodontitis was not
      associated with serum PTH in the case-control data or at the baseline of the
      intervention data. A post-therapy increase in serum PTH was found in 61% of the
      T1DM patients; in patients with moderate or severe periodontitis (n = 26) the
      average increase was 0.6 pmol/l (p = 0.016) and in patients with no or mild
      periodontitis (n = 27) 0.2 pmol/l (p = 0.250). In 47% of the T1DM patients, an
      increase in PTH was associated with an increase in serum 1,25(OH)2 D. CONCLUSION:
      An association between serum PTH and periodontal infection was found only after
      periodontal therapy in T1DM patients. This post-treatment response in serum PTH
      may partly explain the previously reported increase in serum 1,25(OH)2 D.

PMID- 26212699
TI  - Transplacental Transmission of Pemphigus Herpetiformis in the Setting of Maternal
      Lymphoma.
AB  - Pemphigus herpetiformis (PH) is characterized by grouped vesicular or papular
      pruritic lesions with histologic and immunopathologic features of pemphigus. PH
      can manifest at any age, and paraneoplastic cases have been reported. We describe
      a healthy boy born with acral crateriform erosions of the hands and feet whose 35
      year-old mother had similar lesions. Biopsies from both patients were most
      consistent with PH. The mother was diagnosed with high-grade B-cell non-Hodgkin
      lymphoma and began chemotherapy with dexamethasone, and her lesions quickly
      improved. The infant had no additional lesions after 3 weeks of age and his acral
      erosions healed. To our knowledge, this is the first report of a diagnosis of PH
      in an infant and the first case of transplacental transmission of PH. This is
      also the first report of paraneoplastic PH in lymphoma. This case adds to the
      growing differential diagnosis of skin disease in postpartum women and their
      neonates.

PMID- 26212700
TI  - A systematic review of the use of expandable cages in the cervical spine.
AB  - Expandable vertebral body replacement cages (VBRs) have been widely used for
      reconstruction of the thoracolumbar spine following corpectomy. However, their
      use in the cervical spine is less common, and currently, no expandable cages on
      the market are cleared or approved by the US Food and Drug Administration for use
      in the cervical spine. The objective of this study was to perform a systematic
      review on the use of expandable cages in the treatment of cervical spine
      pathology with a focus on fusion rates, deformity correction, complications, and
      indications. A comprehensive Medline search was performed, and 24 applicable
      articles were identified and included in this review. The advantages of
      expandable cages include greater ease of implantation with less risk of damage to
      the end plate, less intraoperative manipulation of the device, and potentially
      greater control over lordosis. They may be particularly advantageous in cases
      with poor bone quality, such as patients with osteoporosis or metastatic tumors
      that have been radiated. However, there is a potential risk of overdistraction,
      which is increased in the cervical spine, their minimum height limits their use
      in cases with collapsed vertebra, and the amount of hardware in the expansion
      mechanism may limit the surface area available for fusion. The use of expandable
      VBRs are a valuable tool in the armamentarium for reconstruction of the anterior
      column of the cervical spine with an acceptable safety profile. Although
      expandable cervical cages are clearly beneficial in certain clinical situations,
      widespread use following all corpectomies is not justified due to their
      significantly greater cost compared to structural bone grafts or non-expandable
      VBRs, which can be utilized to achieve similar clinical outcomes. 

PMID- 26212701
TI  - Extraneural metastases in glioblastoma patients: two cases with YKL-40-positive
      glioblastomas and a meta-analysis of the literature.
AB  - Glioblastoma (GBM) are high-grade gliomas that severely impact on overall
      survival (OS). GBM cell motility and the breakdown of the blood-brain barrier
      could favor GBM cell communication with the systemic circulation. In spite of
      this, extracranial GBM metastases are rare. Here, we describe two YKL-40-positive
      GBM patients with extra-CNS (central nervous system) metastases, and we present a
      meta-analysis of 94 cases. The analysis concluded that extra-CNS metastases
      occurred 8.5 months after first GBM diagnosis and OS was 12 months; surgical GBM
      excision was associated at a longer interval to extra-CNS metastasis than biopsy
      only, and even longer if followed by radiotherapy and chemotherapy. Both our case
      reports were adult males who developed extra-CNS, YKL-40-positive metastases at
      lymph nodes, lung and subcutaneous sites, after 86 and 24 months from initial
      diagnosis of GBM. At first GBM local recurrence, they were treated with
      bevacizumab (BV), an anti-vascular endothelial growth factor antibody. They died
      after 4 and 1 month from the occurrence of metastases. Both cases expressed YKL
      40 and lacked EGFR amplification, suggesting a mesenchymal phenotype, and
      maintained such profile at extra-CNS recurrence; they did not show MGMT promoter
      methylation, IDH1/2 mutations, or c-Met upregulation. Our two cases and the meta
      analysis support the idea that prolonged survival of GBM patients increases the
      probability of GBM cells shedding to lymphatic and hematic system. Interestingly,
      the present two cases showed the features of mesenchymal profile, usually related
      with worst prognosis that was maintained in extracranial metastases.

PMID- 26212702
TI  - Competing Repressive Factors Control Bone Morphogenetic Protein 2 (BMP2) in
      Mesenchymal Cells.
AB  - The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis
      influences the differentiation of pluripotent mesenchymal cells in embryos and
      adults. The BMP2 3'untranslated region (3'UTR) contains a highly conserved AU
      rich element (ARE) embedded in a sequence that commonly represses gene expression
      in mesenchymal cells. Computational analyses indicate that this site also may
      bind several microRNAs (miRNAs). Although miRNAs frequently target AU-rich
      regions, this ARE is unusual because the miRNAs directly span the ARE. We began
      to characterize the factors that may regulate Bmp2 expression via this complex
      site. The activating protein HuR (Hu antigen R, ELAVL1, HGNC:3312) directly binds
      this ARE and can activate gene expression. An miRNA was demonstrated to reverse
      HuR-mediated activation. Mutational and RNA-interference evidence also supports
      an AUF1 (AU-factor-1, HNRNPD, HGNC:5036) contribution to the observed repressive
      activity of the 3'UTR in mesenchymal cells. A limited number of studies describe
      how miRNAs interact with ARE-binding proteins that bind adjacent sites. This
      study is among the first to describe protein/miRNA interactions at the same site.

PMID- 26212704
TI  - Elevated dopamine concentration in light-adapted zebrafish retinas is correlated
      with increased dopamine synthesis and metabolism.
AB  - Probing zebrafish (Danio rerio) retinal cryostat sections, collected either 8 h
      into the light or dark cycle, with an antibody against tyrosine hydroxylase (TH)
      identified a single population of immunopositive cells in the inner retina.
      However, the observed labeling patterns were not identical in both sets of
      tissues - label intensity was brighter in light-adapted tissue. This difference
      was quantified by probing western blots of retinal homogenates with the same TH
      antibody, which showed that TH expression increased by 42% in light-adapted
      tissue. High-performance liquid chromatography with electrochemical detection
      revealed that the concentrations of both dopamine and 3,4-dihydroxyphenylacetic
      acid (DOPAC) are also elevated in light-adapted zebrafish retinal tissue.
      Dopamine levels increased by 14% and DOPAC levels increased by 25% when measured
      in retinal homogenates harvested during the light cycle. These results indicate
      that dopamine levels in zebrafish retina are significantly increased in light
      adapted tissue. The increase in dopamine content is correlated with an increase
      in both TH and DOPAC, suggesting that changes in dopamine concentration are due
      to light-adaptive changes in the synthesis, release and metabolism of dopamine.
      Dopamine concentration is elevated in lighted-adapted zebrafish retinas. This
      increase is correlated with an increase in both tyrosine hydroxylase (TH) and
      DOPAC (3,4-dihydroxyphenylacetic acid), suggesting that changes in dopamine
      concentration are due to light-adaptive changes in the synthesis, release and
      metabolism of dopamine. This is applicable to studies examining retinal mutants,
      the role of dopamine in disease or visual system development. 

PMID- 26212703
TI  - Comparison of a qualitative measurement of heart-type fatty acid-binding protein
      with other cardiac markers as an early diagnostic marker in the diagnosis of non
      ST-segment elevation myocardial infarction.
AB  - OBJECTIVE: Heart-type fatty acid-binding protein (H-FABP) is a novel cardiac
      marker used in the early diagnosis of acute myocardial infarction (AMI), which
      shows myocyte injury. Our study aimed to compare bedside H-FABP measurements with
      routine creatine kinase-MB (CK-MB) and troponin I (TnI) tests for the early
      diagnosis of non-ST-elevation MI (NSTEMI), as well as for determining its
      exclusion capacity. METHODS: A total of 48 patients admitted to the emergency
      room within the first 12 hours of onset of ischaemic-type chest pain lasting more
      than 30 minutes and who did not have ST-segment elevation on electrocardiography
      (ECG) were included in the study. Definite diagnoses of NSTEMI were made in 24
      patients as a result of 24-hour follow up, and the remaining 24 patients did not
      develop MI. RESULTS: When various subgroups were analysed according to admission
      times, H-FABP was found to be a better diagnostic marker compared to CK-MB and
      TnI (accuracy index 85%), with a high sensitivity (79%) and specificity (93%) for
      early diagnosis ( <= six hours). The respective sensitivities of bedside H-FABP
      and TnI tests were 89 vs 33% (p < 0.05) for patients presenting within three
      hours of onset of symptoms. CONCLUSION: Bedside H-FABP measurements may
      contribute to correct early diagnoses, as its levels are elevated soon following
      MI, and measurement is easy, with a rapid result.

PMID- 26212705
TI  - Three-dimensional nanometre localization of nanoparticles to enhance super
      resolution microscopy.
AB  - Meeting the nanometre resolution promised by super-resolution microscopy
      techniques (pointillist: PALM, STORM, scanning: STED) requires stabilizing the
      sample drifts in real time during the whole acquisition process. Metal
      nanoparticles are excellent probes to track the lateral drifts as they provide
      crisp and photostable information. However, achieving nanometre axial super
      localization is still a major challenge, as diffraction imposes large depths-of
      fields. Here we demonstrate fast full three-dimensional nanometre super
      localization of gold nanoparticles through simultaneous intensity and phase
      imaging with a wavefront-sensing camera based on quadriwave lateral shearing
      interferometry. We show how to combine the intensity and phase information to
      provide the key to the third axial dimension. Presently, we demonstrate even in
      the occurrence of large three-dimensional fluctuations of several microns,
      unprecedented sub-nanometre localization accuracies down to 0.7 nm in lateral and
      2.7 nm in axial directions at 50 frames per second. We demonstrate that nanoscale
      stabilization greatly enhances the image quality and resolution in direct
      stochastic optical reconstruction microscopy imaging. 

PMID- 26212706
TI  - Photocatalysis using a Wide Range of the Visible Light Spectrum: Hydrogen
      Evolution from Doped AgGaS2.
AB  - Doping of nickel into AgGaS2 yields a new absorption band, at a wavelength longer
      than the intrinsic absorption band of the AgGaS2 host. The doped nickel forms an
      electron donor level in a forbidden band of AgGaS2 . The nickel-doped AgGaS2 with
      rhodium co-catalyst shows photocatalytic activity for sacrificial H2 evolution
      under the light of up to 760 nm due to the transition from the electron donor
      level consisting of Ni(2+) to the conduction band of AgGaS2 . Apparent quantum
      yields for the sacrificial H2 evolution at 540-620 nm are about 1 %. Moreover,
      the nickel-doped AgGa0.75 In0.25 S2 also responds to near-IR light, up to 900 nm.

PMID- 26212707
TI  - Recurrent secondary generalization in frontal lobe epilepsy: Predictors and a
      potential link to surgical outcome?
AB  - OBJECTIVE: Frontal lobe epilepsy (FLE) frequently leads to secondary generalized
      tonic-clonic seizures (SGTCS). However, little is known about the clinical,
      electrophysiologic, and radiologic correlates of SGTCS and whether these could
      influence diagnosis and treatment. METHODS: A cohort of 48 patients with
      confirmed FLE was retrospectively identified and dichotomized into a group with
      and a group without SGTCS defined by history (>=1/year) or video
      electroencephalography (vEEG). Demographics, seizure semiology, vEEG,
      neuroimaging data, and estimated seizure-onset zone were tabulated, and their
      association with the occurrence of SGTCS was evaluated with use of a chi-square
      test. Independent predictors of SGTCS were confirmed using a stepwise
      multivariate analysis. Similarly, these predictors as well as a history of SGTCS
      were tested as multivariate predictors of the postoperative International League
      Against Epilepsy (ILAE) score in the surgical subgroup (n = 25). RESULTS: We
      identified three independent predictors of a history of SGTCS in FLE, including
      loss of responsiveness at seizure onset (corrected p = 0.04), a semiology
      involving early elementary motor signs (corrected p = 0.01), and multifocal
      spikes on EEG (corrected p = 0.02). A seizure-free outcome occurred in 57% of
      surgical cases and was more likely in the group without SGTCS (100%, p = 0.001).
      When considering only SGTCS occurring during video-EEG monitoring, the
      association with semiology and surgical outcome vanished, but the association
      with preserved awareness and a multifocal EEG persisted. SIGNIFICANCE: A history
      of SGTCS is related to a specific ictal semiology and interictal EEG, and may
      have a role in surgical risk stratification.

PMID- 26212708
TI  - Recognition of DNA/RNA bulges by antimicrobial and antitumor metallohelices.
AB  - Bulged structures have been identified in nucleic acids and have been shown to be
      linked to biomolecular processes involved in numerous diseases. Thus, chemical
      agents with affinity for bulged nucleic acids are of general biological
      significance. Herein, the mechanism of specific recognition and stabilization of
      bulged DNA and RNA by helical bimetallic species was established through detailed
      molecular biophysics and biochemistry assays. These agents, known as
      'flexicates', are potential mimetics of alpha-helical peptides in cancer
      treatment, exhibiting antimicrobial and antitumor effects. The flexicates have
      positive impacts on the thermal stability of DNA duplexes containing bulges,
      which means that the flexicates interact with the duplexes containing bulges, and
      that these interactions stabilize the secondary structures of these duplexes.
      Notably, the stabilising effect of the flexicates increases with the size of the
      bulge, the maximal stabilization is observed for the duplexes containing a bulge
      composed of at least three bases. The flexicates bind most preferentially to the
      bulges composed of pyrimidines flanked on both sides also by pyrimidines. It is
      suggested that it is so because these bulges exhibit greatest conformational
      variability in comparison with other combinations of bases in the bulge loop and
      bases flanking the bulge. Finally, the results indicate that there is only one
      dominant binding site for the flexicates on the DNA and RNA bulges and that the
      flexicates bind directly to the bulge or in its close proximity. It is also shown
      that the flexicates effectively bind to RNA duplexes containing the bulged region
      of HIV-1 TAR RNA. 

PMID- 26212709
TI  - Modulation of Presynaptic Release Probability by the Vertebrate-Specific Protein
      Mover.
AB  - Mover, a member of the exquisitely small group of vertebrate-specific presynaptic
      proteins, has been discovered as an interaction partner of the scaffolding
      protein Bassoon, yet its function has not been elucidated. We used adeno
      associated virus (AAV)-mediated shRNA expression to knock down Mover in the calyx
      of Held in vivo. Although spontaneous synaptic transmission remained unaffected,
      we found a strong increase of the evoked EPSC amplitude. The size of the readily
      releasable pool was unaltered, but short-term depression was accelerated and
      enhanced, consistent with an increase in release probability after Mover
      knockdown. This increase in release probability was not caused by alterations in
      Ca(2+) influx but rather by a higher Ca(2+) sensitivity of the release machinery,
      as demonstrated by presynaptic Ca(2+) uncaging. We therefore conclude that Mover
      expression in certain subsets of synapses negatively regulates synaptic release
      probability, constituting a novel mechanism to tune synaptic transmission. 

PMID- 26212710
TI  - The Nature of Shared Cortical Variability.
AB  - Neuronal responses of sensory cortex are highly variable, and this variability is
      correlated across neurons. To assess how variability reflects factors shared
      across a neuronal population, we analyzed the activity of many simultaneously
      recorded neurons in visual cortex. We developed a simple model that comprises two
      sources of shared variability: a multiplicative gain, which uniformly scales each
      neuron's sensory drive, and an additive offset, which affects different neurons
      to different degrees. This model captured the variability of spike counts and
      reproduced the dependence of pairwise correlations on neuronal tuning and
      stimulus orientation. The relative contributions of the additive and
      multiplicative fluctuations could vary over time and had marked impact on
      population coding. These observations indicate that shared variability of
      neuronal populations in sensory cortex can be largely explained by two factors
      that modulate the whole population. 

PMID- 26212711
TI  - Functional System and Areal Organization of a Highly Sampled Individual Human
      Brain.
AB  - Resting state functional MRI (fMRI) has enabled description of group-level
      functional brain organization at multiple spatial scales. However, cross-subject
      averaging may obscure patterns of brain organization specific to each individual.
      Here, we characterized the brain organization of a single individual repeatedly
      measured over more than a year. We report a reproducible and internally valid
      subject-specific areal-level parcellation that corresponds with subject-specific
      task activations. Highly convergent correlation network estimates can be derived
      from this parcellation if sufficient data are collected-considerably more than
      typically acquired. Notably, within-subject correlation variability across
      sessions exhibited a heterogeneous distribution across the cortex concentrated in
      visual and somato-motor regions, distinct from the pattern of intersubject
      variability. Further, although the individual's systems-level organization is
      broadly similar to the group, it demonstrates distinct topological features.
      These results provide a foundation for studies of individual differences in
      cortical organization and function, especially for special or rare individuals.
      VIDEO ABSTRACT. 

PMID- 26212713
TI  - Individual psychological therapy in the outpatient treatment of adults with
      anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa is a disorder with high morbidity and significant
      mortality. It is most common in young adult women, in whom the incidence may be
      increasing. The focus of treatment has moved to an outpatient setting, and a
      number of differing psychological therapies are presently used in treatment. This
      is an update of a Cochrane review which was last published in 2008. OBJECTIVES:
      To assess the effects of specific individual psychological therapies for anorexia
      nervosa in adults or older adolescents treated in an outpatient setting. SEARCH
      METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group
      Specialised Register (CCDANCTR) (16 July 2014). This register includes relevant
      randomised controlled trials from: the Cochrane Library (all years), MEDLINE
      (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). We screened
      reference lists of all included studies and sent letters to identified, notable
      researchers requesting information on unpublished or ongoing studies. SELECTION
      CRITERIA: All randomised controlled trials of one or more individual outpatient
      psychological therapies for adults with anorexia nervosa, as defined by DSM-5 or
      similar international criteria. DATA COLLECTION AND ANALYSIS: We selected a range
      of outcome variables, including physical state, severity of eating disorder
      attitudes and beliefs, interpersonal function, and general psychiatric symptom
      severity. Continuous outcome data comparisons used the mean or standardised mean
      difference (MD or SMD), and binary outcome comparisons used the risk ratio (RR).
      Two review authors (PH and AC or ST) extracted data independently. MAIN RESULTS:
      We identified 10 trials from the search, with a total of 599 anorexia nervosa
      participants, and included them in the review. Seven had been identified in the
      previous versions of this review and we now include three new trials. We now deem
      one previously identified ongoing trial to be ineligible, and six ongoing trials
      are new for this update. Two of the 10 trials included children. Trials tested
      diverse psychological therapies and comparability was poor. Risks of bias were
      mostly evident through lack of blinded outcome assessments (in 60% of studies)
      and incomplete data reporting (attrition bias).The results suggest that treatment
      as usual (TAU) when delivered by a non-eating-disorder specialist or similar may
      be less efficacious than focal psychodynamic therapy. This was suggested for a
      primary outcome of recovery by achievement of a good or intermediate outcome on
      the Morgan and Russell Scale (RR 0.70, 95% confidence interval (CI) 0.51 to 0.97;
      1 RCT, 40 participants; very low-quality evidence). However there were no
      differences between cognitive analytic therapy and TAU for this outcome (RR 0.78,
      95% CI 0.61 to 1.00; 2 RCTs, 71 participants; very low-quality evidence), nor for
      body mass index (BMI). There were no differences in overall dropout rates between
      individual psychological therapies and TAU.Two trials found a non-specific
      specialist therapy (Specialist Supportive Clinical Management) or an Optimised
      TAU delivered by therapists with eating disorder expertise was similar in
      outcomes to cognitive behaviour therapy (BMI MD -0.00, 95% CI -0.91 to 0.91; 197
      participants, low-quality evidence). When comparing individual psychological
      therapies with each other, no specific treatment was consistently superior to any
      other specific approach. Dietary advice as a control arm had a 100% non
      completion rate in one trial (35 participants). None of the trials identified any
      adverse effects. Insufficient power was problematic for the majority of trials.
      AUTHORS' CONCLUSIONS: There was a suggestion in one trial that focal
      psychodynamic therapy might be superior to TAU, but this is in the context of TAU
      performing poorly. An alternative control condition of dietary advice alone
      appeared to be unacceptable, but again this is based on just one trial. Owing to
      the risk of bias and limitations of studies, notably small sample sizes, we can
      draw no specific conclusions about the effects of specific individual
      psychological therapies for anorexia nervosa in adults or older adolescents.
      Larger RCTs of longer treatment duration and follow-up are needed.

PMID- 26212712
TI  - CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress
      Induced Anxiety.
AB  - The locus coeruleus noradrenergic (LC-NE) system is one of the first systems
      engaged following a stressful event. While numerous groups have demonstrated that
      LC-NE neurons are activated by many different stressors, the underlying neural
      circuitry and the role of this activity in generating stress-induced anxiety has
      not been elucidated. Using a combination of in vivo chemogenetics, optogenetics,
      and retrograde tracing, we determine that increased tonic activity of the LC-NE
      system is necessary and sufficient for stress-induced anxiety and aversion.
      Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety
      like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE
      neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore,
      endogenous corticotropin-releasing hormone(+) (CRH(+)) LC inputs from the
      amygdala increase tonic LC activity, inducing anxiety-like behaviors. These
      studies position the LC-NE system as a critical mediator of acute stress-induced
      anxiety and offer a potential intervention for preventing stress-related
      affective disorders. 

PMID- 26212714
TI  - Comparison of self-administered survey questionnaire responses collected using
      mobile apps versus other methods.
AB  - BACKGROUND: Self-administered survey questionnaires are an important data
      collection tool in clinical practice, public health research and epidemiology.
      They are ideal for achieving a wide geographic coverage of the target population,
      dealing with sensitive topics and are less resource-intensive than other data
      collection methods. These survey questionnaires can be delivered electronically,
      which can maximise the scalability and speed of data collection while reducing
      cost. In recent years, the use of apps running on consumer smart devices (i.e.,
      smartphones and tablets) for this purpose has received considerable attention.
      However, variation in the mode of delivering a survey questionnaire could affect
      the quality of the responses collected. OBJECTIVES: To assess the impact that
      smartphone and tablet apps as a delivery mode have on the quality of survey
      questionnaire responses compared to any other alternative delivery mode: paper,
      laptop computer, tablet computer (manufactured before 2007), short message
      service (SMS) and plastic objects. SEARCH METHODS: We searched MEDLINE, EMBASE,
      PsycINFO, IEEEXplore, Web of Science, CABI: CAB Abstracts, Current Contents
      Connect, ACM Digital, ERIC, Sociological Abstracts, Health Management Information
      Consortium, the Campbell Library and CENTRAL. We also searched registers of
      current and ongoing clinical trials such as ClinicalTrials.gov and the World
      Health Organization (WHO) International Clinical Trials Registry Platform. We
      also searched the grey literature in OpenGrey, Mobile Active and ProQuest
      Dissertation & Theses. Lastly, we searched Google Scholar and the reference lists
      of included studies and relevant systematic reviews. We performed all searches up
      to 12 and 13 April 2015. SELECTION CRITERIA: We included parallel randomised
      controlled trials (RCTs), crossover trials and paired repeated measures studies
      that compared the electronic delivery of self-administered survey questionnaires
      via a smartphone or tablet app with any other delivery mode. We included data
      obtained from participants completing health-related self-administered survey
      questionnaire, both validated and non-validated. We also included data offered by
      both healthy volunteers and by those with any clinical diagnosis. We included
      studies that reported any of the following outcomes: data equivalence; data
      accuracy; data completeness; response rates; differences in the time taken to
      complete a survey questionnaire; differences in respondent's adherence to the
      original sampling protocol; and acceptability to respondents of the delivery
      mode. We included studies that were published in 2007 or after, as devices that
      became available during this time are compatible with the mobile operating system
      (OS) framework that focuses on apps. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data from the included studies using a
      standardised form created for this systematic review in REDCap. They then
      compared their forms to reach consensus. Through an initial systematic mapping on
      the included studies, we identified two settings in which survey completion took
      place: controlled and uncontrolled. These settings differed in terms of (i) the
      location where surveys were completed, (ii) the frequency and intensity of
      sampling protocols, and (iii) the level of control over potential confounders
      (e.g., type of technology, level of help offered to respondents). We conducted a
      narrative synthesis of the evidence because a meta-analysis was not appropriate
      due to high levels of clinical and methodological diversity. We reported our
      findings for each outcome according to the setting in which the studies were
      conducted. MAIN RESULTS: We included 14 studies (15 records) with a total of 2275
      participants; although we included only 2272 participants in the final analyses
      as there were missing data for three participants from one included
      study.Regarding data equivalence, in both controlled and uncontrolled settings,
      the included studies found no significant differences in the mean overall scores
      between apps and other delivery modes, and that all correlation coefficients
      exceeded the recommended thresholds for data equivalence. Concerning the time
      taken to complete a survey questionnaire in a controlled setting, one study found
      that an app was faster than paper, whereas the other study did not find a
      significant difference between the two delivery modes. In an uncontrolled
      setting, one study found that an app was faster than SMS. Data completeness and
      adherence to sampling protocols were only reported in uncontrolled settings.
      Regarding the former, an app was found to result in more complete records than
      paper, and in significantly more data entries than an SMS-based survey
      questionnaire. Regarding adherence to the sampling protocol, apps may be better
      than paper but no different from SMS. We identified multiple definitions of
      acceptability to respondents, with inconclusive results: preference; ease of use;
      willingness to use a delivery mode; satisfaction; effectiveness of the system
      informativeness; perceived time taken to complete the survey questionnaire;
      perceived benefit of a delivery mode; perceived usefulness of a delivery mode;
      perceived ability to complete a survey questionnaire; maximum length of time that
      participants would be willing to use a delivery mode; and reactivity to the
      delivery mode and its successful integration into respondents' daily routine.
      Finally, regardless of the study setting, none of the included studies reported
      data accuracy or response rates. AUTHORS' CONCLUSIONS: Our results, based on a
      narrative synthesis of the evidence, suggest that apps might not affect data
      equivalence as long as the intended clinical application of the survey
      questionnaire, its intended frequency of administration and the setting in which
      it was validated remain unchanged. There were no data on data accuracy or
      response rates, and findings on the time taken to complete a self-administered
      survey questionnaire were contradictory. Furthermore, although apps might improve
      data completeness, there is not enough evidence to assess their impact on
      adherence to sampling protocols. None of the included studies assessed how
      elements of user interaction design, survey questionnaire design and intervention
      design might influence mode effects. Those conducting research in public health
      and epidemiology should not assume that mode effects relevant to other delivery
      modes apply to apps running on consumer smart devices. Those conducting
      methodological research might wish to explore the issues highlighted by this
      systematic review.

PMID- 26212715
TI  - Evaluation of Vibration Response Imaging (VRI) Technique and Difference in VRI
      Indices Among Non-Smokers, Active Smokers and Passive Smokers.
AB  - BACKGROUND: Vibration response imaging (VRI) is a new technology for lung
      imaging. Active smokers and non-smokers show differences in VRI findings, but no
      data are available for passive smokers. The aim of this study was to evaluate the
      use of VRI and to assess the differences in VRI findings among non-smokers,
      active smokers, and passive smokers. MATERIAL AND METHODS: Healthy subjects
      (n=165: 63 non-smokers, 56 active smokers, and 46 passive smokers) with normal
      lung function were enrolled. Medical history, physical examination, lung function
      test, and VRI were performed for all subjects. Correlation between smoking index
      and VRI scores (VRIS) were performed. RESULTS: VRI images showed progressive and
      regressive stages representing the inspiratory and expiratory phases bilaterally
      in a vertical and synchronized manner in non-smokers. Vibration energy curves
      with low expiratory phase and plateau were present in 6.35% and 3.17%,
      respectively, of healthy non-smokers, 41.07% and 28.60% of smokers, and 39.13%
      and 30.43% of passive smokers, respectively. The massive energy peak in the non
      smokers, smokers, and passive-smokers was 1.77+/-0.27, 1.57+/-0.29, and 1.66+/
      0.33, respectively (all P<0.001). A weak but positive correlation was observed
      between VRIS and smoking index. CONCLUSIONS: VRI can intuitively show the
      differences between non-smokers and smokers. VRI revealed that passive smoking
      can also harm the lungs. VRI could be used to visually persuade smokers to give
      up smoking.

PMID- 26212716
TI  - Hypoxia-Mediated Increases in L-2-hydroxyglutarate Coordinate the Metabolic
      Response to Reductive Stress.
AB  - Metabolic adaptation to hypoxia is critical for survival in metazoan species for
      which reason they have developed cellular mechanisms for mitigating its adverse
      consequences. Here, we have identified L-2-hydroxyglutarate (L2HG) as a universal
      adaptive determinant of the hypoxia response. L2HG is a metabolite of unknown
      function produced by the reduction of mitochondrial 2-oxoglutarate by malate
      dehydrogenase. L2HG accumulates in response to increases in 2-oxoglutarate, which
      occur as a result of tricarboxylic acid cycle dysfunction and increased
      mitochondrial reducing potential. These changes are closely coupled to cellular
      redox homeostasis, as increased cellular L2HG inhibits electron transport and
      glycolysis to offset the adverse consequences of mitochondrial reductive stress
      induced by hypoxia. Thus, L2HG couples mitochondrial and cytoplasmic energy
      metabolism in a model of cellular redox regulation.

PMID- 26212718
TI  - Glucoregulatory Relevance of Small Intestinal Nutrient Sensing in Physiology,
      Bariatric Surgery, and Pharmacology.
AB  - Emerging evidence suggests the gastrointestinal tract plays an important
      glucoregulatory role. In this perspective, we first review how the intestine
      senses ingested nutrients, initiating crucial negative feedback mechanisms
      through a gut-brain neuronal axis to regulate glycemia, mainly via reduction in
      hepatic glucose production. We then highlight how intestinal energy sensory
      mechanisms are responsible for the glucose-lowering effects of bariatric surgery,
      specifically duodenal-jejunal bypass, and the antidiabetic agents metformin and
      resveratrol. A better understanding of these pathways lays the groundwork for
      intestinally targeted drug therapy for the treatment of diabetes. 

PMID- 26212717
TI  - Hypoxia Induces Production of L-2-Hydroxyglutarate.
AB  - Somatic mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2) contribute to the
      pathogenesis of cancer via production of the "oncometabolite" D-2
      hydroxyglutarate (D-2HG). Elevated D-2HG can block differentiation of malignant
      cells by functioning as a competitive inhibitor of alpha-ketoglutarate (alpha-KG)
      dependent enzymes, including Jumonji family histone lysine demethylases. 2HG is a
      chiral molecule that can exist in either the D-enantiomer or the L-enantiomer.
      Although cancer-associated IDH1/2 mutants produce D-2HG, biochemical studies have
      demonstrated that L-2HG also functions as a potent inhibitor of alpha-KG
      dependent enzymes. Here we report that under conditions of oxygen limitation,
      mammalian cells selectively produce L-2HG via enzymatic reduction of alpha-KG.
      Hypoxia-induced L-2HG is not mediated by IDH1 or IDH2, but instead results from
      promiscuous substrate usage primarily by lactate dehydrogenase A (LDHA). During
      hypoxia, the resulting increase in L-2HG is necessary and sufficient for the
      induction of increased methylation of histone repressive marks, including histone
      3 lysine 9 (H3K9me3). 

PMID- 26212719
TI  - The effect of compression socks worn during a marathon on hemostatic balance.
AB  - INTRODUCTION: Marathon running evokes parallel increases in markers of
      coagulation and fibrinolysis (i.e. hemostatic activation) immediately following
      strenuous, endurance exercise such that hemostatic balance is maintained.
      However, other factors incident to marathon running (i.e. dehydration, travel)
      may disproportionately activate the coagulatory system, increasing blood clot
      risk after an endurance event in otherwise healthy individuals. We investigated
      the effect of compression socks on exercise-induced hemostatic activation and
      balance in endurance athletes running the 2013 Hartford Marathon. METHODS: Adults
      (n = 20) were divided into compression sock (SOCK; n = 10) and control (CONTROL;
      n = 10) groups. Age, anthropometrics, vital signs, training mileage and finishing
      time were collected. Venous blood samples were collected 1 day before,
      immediately after and 1 day following the marathon for analysis of coagulatory
      (i.e. thrombin-antithrombin complex [TAT] and D-dimer) and fibrinolytic (i.e.
      tissue plasminogen activator [t-PA]) factors. RESULTS: Plasma D-dimer, TAT and t
      PA did not differ between groups at baseline (p > 0.16). There were no
      significant group . time interactions (all p >= 0.17), however, average t-PA was
      lower in SOCK (8.9 +/- 0.7 ng/mL) than CONTROL (11.2 +/- 0.7 ng/mL) (p = 0.04).
      Average TAT also tended to be lower in SOCK (2.8 +/- 0.2 ug/L) than CONTROL (3.4
      +/- 0.2 ug/L) (p = 0.07). CONCLUSIONS: Our results suggest that overall
      hemostatic activation (both coagulation and fibrinolysis) following a marathon
      tended to be lower with compression socks. Thus, compression socks do not
      adversely influence markers of hemostasis, appear safe for overall use in runners
      and may reduce exercise-associated hemostatic activation in individuals at risk
      for deep vein thrombosis.

PMID- 26212720
TI  - High-dose therapy improves the bone remodelling compartment canopy coverage and
      bone formation in multiple myeloma.
AB  - Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation
      to resorption trigged by malignant plasma cells. Increasing evidence indicates
      that the bone remodelling compartment (BRC) canopy, which normally covers the
      remodelling sites, is important for coupled bone remodelling. Loss of this canopy
      has been associated with bone loss. This study addresses whether the bone
      remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained
      from 20 MM patients, before and after first-line treatment with high-dose
      melphalan followed by autologous stem cell transplantation, and from 20 control
      patients with monoclonal gammopathy of undetermined significance were
      histomorphometrically investigated. This investigation confirmed that MM patients
      exhibited uncoupled bone formation to resorption and reduced canopy coverage.
      More importantly, this study revealed that a good response to anti-myeloma
      treatment increased the extent of formative bone surfaces with canopy, and
      reduced the extent of eroded surfaces without canopy, reverting the uncoupled
      bone remodelling, while improving canopy coverage. The association between
      improved coupling and the canopy coverage supports the notion that canopies are
      critical for the coupling of bone formation to resorption. Furthermore, this
      study supports the observation that systemic bone disease in MM can be reversed
      in MM patients responding to anti-myeloma treatment. 

PMID- 26212721
TI  - Goat cathelicidin-2 is secreted by blood leukocytes regardless of
      lipopolysaccharide stimulation.
AB  - It has been reported that goat cathelicidin-2, an antimicrobial peptide,
      localizes in leukocytes and is present in milk. Here, we examined whether
      cathelicidin-2 is secreted by leukocytes. Different concentrations (10(5)-10(8)
      cells/mL) of blood leukocytes were cultured for 0-48 h with or without
      lipopolysaccharide (LPS). After culture, the concentrations of cathelicidin-2 in
      the conditioned media were measured. Blood was collected from male goats 0-24 h
      after the intravenous injection of Escherichia coli O111:B4 LPS. The plasma
      cathelicidin-2 concentrations were determined and the blood leukocytes
      immunostained with anti-cathelicidin-2 antibody to calculate the proportion of
      cathelicidin-2-positive cells in the total leukocytes. When higher concentrations
      of leukocytes were cultured, the cathelicidin-2 concentrations in the media
      increased significantly, whereas the addition of LPS to the media caused no
      further increase. The plasma cathelicidin-2 concentrations did not increase with
      time after LPS infusion. The proportion of cathelicidin-2-positive cells in the
      total leukocytes was significantly reduced 1 h after LPS injection compared with
      that at 0 h, but increased again at 6 h and thereafter. These results suggest
      that cathlicidin-2 is secreted by leukocytes even without LPS stimulation,
      whereas LPS may be required for cathelicidin-2-containing leukocytes to be
      recruited from the blood to tissues showing inflammation.

PMID- 26212722
TI  - In vitro phenotypic differentiation towards commensal and pathogenic oral
      biofilms.
AB  - Commensal oral biofilms, defined by the absence of pathology-related phenotypes,
      are ubiquitously present. In contrast to pathological biofilms commensal biofilms
      are rarely studied. Here, the effect of the initial inoculum and subsequent
      growth conditions on in vitro oral biofilms was studied. Biofilms were inoculated
      with saliva and grown anaerobically for up to 21 days in McBain medium with or
      without fetal calf serum (FCS) or sucrose. Pathology-related phenotypes were
      quantified and the community composition was determined. Biofilms inoculated with
      pooled saliva or individual inocula were similar. Denaturing gradient gel
      electrophoresis (DGGE) analysis allowed differentiation of biofilms grown with
      sucrose, but not with FCS. Lactate production by biofilms was significantly
      increased by sucrose and protease activity by FCS. McBain grown biofilms showed
      low activity for both phenotypes. Three clinically relevant in vitro biofilm
      models were developed and could be differentiated based on pathology-related
      phenotypes but not DGGE analysis. These models allow analysis of health-to
      disease shifts and the effectiveness of prevention measures. 

PMID- 26212723
TI  - Fast and General Method To Predict the Physicochemical Properties of Druglike
      Molecules Using the Integral Equation Theory of Molecular Liquids.
AB  - We report a method to predict physicochemical properties of druglike molecules
      using a classical statistical mechanics based solvent model combined with machine
      learning. The RISM-MOL-INF method introduced here provides an accurate technique
      to characterize solvation and desolvation processes based on solute-solvent
      correlation functions computed by the 1D reference interaction site model of the
      integral equation theory of molecular liquids. These functions can be obtained in
      a matter of minutes for most small organic and druglike molecules using existing
      software (RISM-MOL) (Sergiievskyi, V. P.; Hackbusch, W.; Fedorov, M. V. J.
      Comput. Chem. 2011, 32, 1982-1992). Predictions of caco-2 cell permeability and
      hydration free energy obtained using the RISM-MOL-INF method are shown to be more
      accurate than the state-of-the-art tools for benchmark data sets. Due to the
      importance of solvation and desolvation effects in biological systems, it is
      anticipated that the RISM-MOL-INF approach will find many applications in
      biophysical and biomedical property prediction. 

PMID- 26212724
TI  - A Population-Based Cohort Study of All-Cause and Site-Specific Cancer Incidence
      Among Patients With Type 1 Diabetes Mellitus in Taiwan.
AB  - BACKGROUND: The relationship between type 1 diabetes mellitus (T1DM) and cancer
      incidence remains unclear. We sought to assess the all-cause and site-specific
      cancer incidence in patients with T1DM. METHODS: A retrospective cohort study
      design was employed, in which 14 619 patients with T1DM were retrieved from
      Taiwan's National Health Insurance medical claims between 2000 and 2007. The
      study subjects were followed to the end of 2008, and cancer incidence was
      assessed. We calculated age-, sex-, and calendar year-standardized incidence
      ratios (SIRs) of all-cause cancer incidence and site-specific neoplasm incidence,
      with reference to the general population. RESULTS: Seven hundred and sixty
      patients were identified for all-cause cancer over 86,610 person-years,
      representing an incidence rate of 87.75 cases per 10,000 person-years. The
      incidence rate was higher in males than in female patients (109.86 vs 69.75 cases
      per 10,000 person-years). T1DM was associated with a significantly increased SIR
      of all-cause cancer (1.13; 95% confidence interval [CI], 1.05-1.22). The sex
      specific SIR was significantly elevated in female patients (1.19; 95% CI, 1.07
      1.33), but the SIR for male patients was insignificantly elevated (1.09; 95% CI,
      0.99-1.20). Pancreatic cancer showed the greatest increase in SIR among both male
      and female patients with T1DM. Male patients experienced significantly increased
      SIRs for kidney, rectum, liver, and colon neoplasm, and significantly increased
      SIRs were noted for ovarian, bladder, and colon cancer in female patients.
      CONCLUSIONS: T1DM was associated with a 13% increase in risk of all-cause cancer
      incidence. Patients with T1DM should be advised to undergo cancer screening for
      certain types of cancer.

PMID- 26212726
TI  - Quality of life in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a chronic multi-system autoimmune disease associated
      with disability and reduced quality of life. There is no effective treatment or
      cure to SSc, so it is important improve global health of these patients and
      reduce morbidity and mortality associated with SSc. It was made a literature
      review about quality of life in patients with SSc, regarding the several factors
      that should be considered and evaluated when attending to SSc patients. It was
      also considered the validated scales and questionnaires used to measure outcomes
      in patients with SSc. We concluded that it is important to have an
      interdisciplinary approach to SSc patients considering the patient's cognitive
      representations of the disease and what they value most like mobility and hand
      function, pain, fatigue, sleep, depression and body image. 

PMID- 26212725
TI  - Association Between Urinary Phthalates and Pubertal Timing in Chinese
      Adolescents.
AB  - BACKGROUND: Phthalates are synthetic chemicals and ubiquitous environmental
      contaminants, with hormonal activity that may alter the course of pubertal
      development in children. OBJECTIVES: To determine whether exposure to phthalate
      metabolites is associated with timing of pubertal development in a cross
      sectional study of a school-based clustered sample of 503 children from a
      suburban district in Shanghai, China, who were 7-14 years of age at enrollment
      (2010 October to November). METHODS: We analyzed six phthalate metabolites in
      urine samples by isotope-dilution liquid chromatography tandem mass spectrometry.
      The associations of exposures to phthalates with pubertal timing of testes,
      breast, and pubic hair development (represented as Tanner stages) were evaluated
      using an ordered logistic regression model adjusted for chronological age, body
      fat proportion (BF%), and parental education. RESULTS: In boys, urinary mono-n
      butyl phthalate (MBP) levels were negatively associated with testicular volume,
      and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono (2-ethyl-5-oxohexyl)
      phthalate (MEOHP) levels were negatively associated with pubic hair stages. The
      odds of being in an advanced stage were decreased by 43%-51%. In girls, mono (2
      ethylhexyl) phthalate (MEHP), MEHHP, and MEOHP levels, as well as the sum of
      these levels, were positively associated with breast stages, and the association
      was much stronger in girls with high BF%; the odds of being in an advanced stage
      were increase by 29% to 50%. CONCLUSIONS: Phthalate metabolites investigated in
      this study show significant associations with pubertal timing both in boys and in
      girls, especially among girls with high BF%.

PMID- 26212727
TI  - The mechanistic impact of CD22 engagement with epratuzumab on B cell function:
      Implications for the treatment of systemic lupus erythematosus.
AB  - Epratuzumab is a B-cell-directed non-depleting monoclonal antibody that targets
      CD22. It is currently being evaluated in two phase 3 clinical trials in patients
      with systemic lupus erythematosus (SLE), a disease associated with abnormalities
      in B-cell function and activation. The mechanism of action of epratuzumab
      involves perturbation of the B-cell receptor (BCR) signalling complex and
      intensification of the normal inhibitory role of CD22 on the BCR, leading to
      reduced signalling and diminished activation of B cells. Such effects may result
      from down-modulation of CD22 upon binding by epratuzumab, as well as decreased
      expression of other proteins involved in amplifying BCR signalling capability,
      notably CD19. The net result is blunting the capacity of antigen engagement to
      induce B-cell activation. The functional consequences of epratuzumab binding to
      CD22 include diminished B-cell proliferation, effects on adhesion molecule
      expression, and B-cell migration, as well as reduced production of pro
      inflammatory cytokines, such as IL-6 and TNF. Studies in patients treated with
      epratuzumab have revealed a number of pharmacodynamic effects that are linked to
      the mechanism of action (i.e., a loss of the target molecule CD22 from the B-cell
      surface followed by a modest reduction in peripheral B-cell numbers after
      prolonged therapy). Together, these data indicate that epratuzumab therapy
      affords a unique means to modulate BCR complex expression and signalling. 

PMID- 26212729
TI  - New insights on the interaction between the isoforms 1 and 2 of human translation
      elongation factor 1A.
AB  - The eukaryotic translation elongation factor 1A (eEF1A) is a moonlighting protein
      that besides to its canonical role in protein synthesis is also involved in many
      other cellular processes such as cell survival and apoptosis. In a previous work,
      we identified eEF1A Raf-mediated phosphorylation sites and defined their role in
      the regulation of eEF1A half-life and apoptosis of human cancer cells. We
      proposed that the phosphorylation of eEF1A by C-Raf required the presence of both
      eEF1A isoforms thus suggesting the formation of a potential eEF1A heterodimer
      owning regulatory properties. This study aimed at investigating the cellular
      localization and interaction between two eEF1A isoforms. To this end, we
      developed chimera proteins by adding at the N-terminal end of both eEF1A1 and
      eEF1A2 cyan fluorescence protein (mCerulean) and yellow fluorescence protein
      (mVenus), respectively. The fluorescent eEF1A1 and eEF1A2 chimeras were both
      addressed to COS-7 cells and found co-localized in the cytoplasm at the level of
      cellular membranes. We highlighted FRET between the labeled N-termini of eEF1A
      isoforms. The intra-molecular FRET of this chimera was about 17%. Our results
      provide novel information on the intracellular distribution and interaction of
      eEF1A isoforms. 

PMID- 26212728
TI  - The Xis2d protein of CTnDOT binds to the intergenic region between the mob and
      tra operons.
AB  - CTnDOT is a 65kbp integrative and conjugative element (ICE) that carries genes
      encoding both tetracycline and erythromycin resistances. The excision operon of
      this element encodes Xis2c, Xis2d, and Exc proteins involved in the excision of
      CTnDOT from host chromosomes. These proteins are also required in the complex
      transcriptional regulation of the divergently transcribed transfer (tra) and
      mobilization (mob) operons of CTnDOT. Transcription of the tra operon is
      positively regulated by Xis2c and Xis2d, whereas, transcription of the mob operon
      is positively regulated by Xis2d and Exc. Xis2d is the only protein that is
      involved in the excision reaction, as well as the transcriptional regulation of
      both the mob and tra operons. This paper helps establish how Xis2d binds the DNA
      in the mob and tra region. Unlike other excisionase proteins, Xis2d binds a
      region of dyad symmetry. The binding site is located in the intergenic region
      between the mob and tra promoters, and once bound Xis2d induces a bend in the
      DNA. Xis2d binding to this region could be the preliminary step for the
      activation of both operons. Then the other proteins, like Exc, can interact with
      Xis2d and form higher order complexes. 

PMID- 26212730
TI  - Suppression of antioxidant Nrf-2 and downstream pathway in H9c2 cells by advanced
      glycation end products (AGEs) via ERK phosphorylation.
AB  - Diabetic cardiomyopathy is related to oxidative stress and correlated with the
      presence of advanced glycation end products (AGEs). In a clinical setting, AGEs
      can be detected in patients presenting diabetic cardiomyopathy; however, the
      underlying mechanism has yet to be elucidated. In our previous study, AGEs
      increase cell hypertrophy via ERK phosphorylation in a process closely related to
      ROS production. Thus, we propose that AGEs regulate the antioxidant gene nuclear
      factor-erythroid 2-related factor (Nrf-2). In H9c2 cells treated with AGEs, the
      expression of Nrf-2 was reduced; however, ERK phosphorylation was shown to
      increase. Treatment with H2O2 was also shown to increase Nrf-2 and ERK
      phosphorylation. In cells pretreatment with ROS scavenger NAC, the effects of
      H2O2 were reduced; however, the effects of the AGEs remained largely unchanged.
      Conversely, when cells were pretreated with PD98059 (ERK inhibitor), the
      expression of Nrf-2 was recovered following treatment with AGEs. Our results
      suggest that AGEs inhibit Nrf-2 via the ERK pathway; however, this influence is
      partly associated with ROS. Our finding further indicated that AGEs possess both
      ROS-dependent and ROS-independent pathways, resulting in a reduction in Nrf-2.
      This report reveals an important mechanism underlying the regulation of diabetic
      cardiomyopathy progression by AGEs. 

PMID- 26212732
TI  - Improving the development of early bovine somatic-cell nuclear transfer embryos
      by treating adult donor cells with vitamin C.
AB  - Vitamin C (Vc) has been widely studied in cell and embryo culture, and has
      recently been demonstrated to promote cellular reprogramming. The objective of
      this study was to identify a suitable Vc concentration that, when used to treat
      adult bovine fibroblasts serving as donor cells for nuclear transfer, improved
      donor-cell physiology and the developmental potential of the cloned embryos that
      the donor nuclei were used to create. A Vc concentration of 0.15 mM promoted cell
      proliferation and increased donor-cell 5-hydroxy methyl cytosine levels 2.73-fold
      (P < 0.05). The blastocyst rate was also significantly improved after nuclear
      transfer (39.6% treated vs. 26.0% control, P < 0.05); the average number of
      apoptotic cells in cloned blastocysts was significantly reduced (2.2 vs. 4.4, P <
      0.05); and the inner cell mass-to-trophectoderm ratio (38.25% vs. 30.75%, P <
      0.05) and expression of SOX2 (3.71-fold, P < 0.05) and POU5F1 (3.15-fold, P <
      0.05) were significantly increased. These results suggested that Vc promotes cell
      proliferation, decreases DNA methylation levels in donor cells, and improves the
      developmental competence of bovine somatic-cell nuclear transfer embryos.

PMID- 26212733
TI  - Lozenge-Induced Hypermineralcorticoid State--A Unique Case of Licorice Lozenges
      Resulting in Hypertension and Hypokalemia.

PMID- 26212734
TI  - 'Judging a book by its cover': An experimental study of the negative impact of a
      diagnosis of borderline personality disorder on clinicians' judgements of
      uncomplicated panic disorder.
AB  - OBJECTIVES: Diagnosis is ubiquitous in Psychiatry, and whilst it does bring
      benefits; adverse effects of 'labelling' may also be possible. This study aimed
      to evaluate experimentally whether clinicians' judgements about a patient with
      panic disorder were influenced by an inappropriately suggested diagnosis of
      comorbid borderline personality disorder (BPD). DESIGN: An experimental design
      was used to evaluate clinician's judgements when the nature of the information
      they were given was varied to imply BPD comorbidity. METHODS: Two hundred and
      sixty-five clinicians watched a video-recorded assessment of a woman describing
      her experience of uncomplicated 'panic disorder' and then rated her present
      problems and likely prognosis. Prior to watching the video recording,
      participants were randomly allocated to one of three conditions with written
      information including the following: (1) her personal details and general
      background; (2) the addition of a behavioural description consistent with BPD;
      and (3) the further addition of a 'label' (past BPD diagnosis). RESULTS: The BPD
      label was associated with more negative ratings of the woman's problems and her
      prognosis than both information alone and a behavioural description of BPD
      'symptoms'. CONCLUSIONS: Regardless of potential actuarial value of such
      diagnoses, it is concluded that clinicians can be overly influenced by past
      diagnostic labels in the context of an apparent current comorbid problem,
      although such biases appear to be less likely if a description of the relevant
      behaviours is used instead. Thus, the label, rather than the behaviour it
      denotes, may be stigmatizing in mental health professionals. PRACTITIONER POINTS:
      Diagnostic labels can have an inappropriately negative effect on clinicians'
      judgements not only of treatment variables such as engagement and response but
      also risk issues and interpersonal effectiveness. Diagnostic labels can have a
      greater effect on clinicians' judgements than a behavioural description or
      clinical presentation. Clinicians should therefore be cautious both in the use of
      diagnostic labels to describe patients and ensure that these are still valid, and
      also be mindful of the influence that such labels can have on their own clinical
      judgements and constantly seek to challenge these. Behavioural descriptions of
      difficulties are less likely to result in such negative judgements and
      predictions.

PMID- 26212737
TI  - Home birth is unsafe: AGAINST: Safe for whom?

PMID- 26212738
TI  - Home birth is unsafe: FOR: The safety of planned homebirths: a clinical fiction.

PMID- 26212739
TI  - The minefield of informed consent.

PMID- 26212740
TI  - The perils of taking written consent for operative delivery during labour.

PMID- 26212741
TI  - The Montgomery ruling extends patient autonomy.

PMID- 26212742
TI  - Author's reply re: The association between the regular use of preventive labour
      induction and improved term birth outcomes.

PMID- 26212743
TI  - Re: The association between the regular use of preventive labour induction and
      improved term birth outcomes: Preventive labour induction.

PMID- 26212744
TI  - Re: Laparoscopic morcellation: an acceptable risk or an Achilles heel? Are there
      safer alternatives to morcellation?

PMID- 26212746
TI  - ?

PMID- 26212745
TI  - A report from #BlueJC: How can we improve global women's health research after
      2015?

PMID- 26212748
TI  - ?

PMID- 26212747
TI  - ?

PMID- 26212749
TI  - ?

PMID- 26212750
TI  - ?

PMID- 26212751
TI  - ?

PMID- 26212752
TI  - ?

PMID- 26212754
TI  - ?

PMID- 26212753
TI  - ?

PMID- 26212755
TI  - Neuropsychological deficits in preschool as predictors of ADHD symptoms and
      academic achievement in late adolescence.
AB  - High levels of ADHD symptoms are related to severe negative outcomes, which
      underscore the importance of identifying early markers of these behavior
      problems. The main aim of the present study was therefore to investigate whether
      neuropsychological deficits in preschool are related to later ADHD symptoms and
      academic achievement, over and above the influence of early ADHD symptom levels.
      The present study is unique because it includes a broader range of predictors
      compared to previous studies and the participants are followed over time for as
      long as 13 years (i.e., ages 5-18 years). Preschool data included measures of
      executive functioning and reaction time variability as well as emotional
      reactivity and emotion regulation of both positive and negative emotions. When
      controlling for early ADHD symptom levels, working memory, reaction time
      variability, and regulation of happiness/exuberance were significantly related to
      inattention whereas regulation of happiness/exuberance and anger reactivity were
      significantly related to hyperactivity/impulsivity. Furthermore, working memory
      and reaction time variability in preschool were significantly related to academic
      achievement in late adolescence beyond the influence of early ADHD symptoms.
      These findings could suggest that it is possible to screen for early
      neuropsychological deficits and thereby identify children who are at risk of
      negative outcomes. Furthermore, our results suggest that interventions need to
      look beyond executive functioning deficits in ADHD and also target the role of
      emotional functioning and reaction time variability. The importance of including
      both the positive and negative aspects of emotional functioning and
      distinguishing between emotion regulation and emotional reactivity was also
      demonstrated.

PMID- 26212756
TI  - Anti-CD antibody microarray for human leukocyte morphology examination allows
      analyzing rare cell populations and suggesting preliminary diagnosis in leukemia.
AB  - We describe a method for leukocyte sorting by a microarray of anti-cluster-of
      differentiation (anti-CD) antibodies and for preparation of the bound cells for
      morphological or cytochemical examination. The procedure results in a "sorted"
      smear with cells positive for certain surface antigens localised in predefined
      areas. The morphology and cytochemistry of the microarray-captured normal and
      neoplastic peripheral blood mononuclear cells are identical to the same
      characteristics in a smear. The microarray permits to determine the proportions
      of cells positive for the CD antigens on the microarray panel with high
      correlation with flow cytometry. Using the anti-CD microarray we show that normal
      granular lymphocytes and lymphocytes with radial segmentation of the nuclei are
      positive for CD3, CD8, CD16 or CD56 but not for CD4 or CD19. We also show that
      the described technique permits to obtain a pure leukemic cell population or to
      separate two leukemic cell populations on different antibody spots and to study
      their morphology or cytochemistry directly on the microarray. In cases of
      leukemias/lymphomas when circulating neoplastic cells are morphologically
      distinct, preliminary diagnosis can be suggested from full analysis of cell
      morphology, cytochemistry and their binding pattern on the microarray. 

PMID- 26212758
TI  - Posterior coronal shear fracture of the distal humerus in a child.

PMID- 26212759
TI  - Elucidating trends in revision reverse total shoulder arthroplasty procedures: a
      retrieval study evaluating clinical, radiographic, and functional outcomes data.
AB  - BACKGROUND: The purpose of this study was to explore relationships between damage
      modes in explanted reverse total shoulder arthroplasty (RTSA) components, patient
      and radiographic risk factors, and functional data to elucidate trends in RTSA
      failure. METHODS: Fifty RTSA systems, retrieved from 44 patients, with 50
      polyethylene (PE) liners, 30 glenospheres, 21 glenoid baseplates, 13 modular
      humeral metaphases, and 17 humeral stems, were examined for damage modes,
      including abrasion, burnishing, dishing, embedding, scratching, and pitting. PE
      liners were also analyzed for delamination and edge deformation. Charts were
      reviewed for patient, surgical, and functional data. Pre-revision radiographs
      were analyzed for scapular notching and loosening. RESULTS: Average term of
      implantation was 20 months (range, 0-81 months). Metallic components exhibited
      abrasion, burnishing, dishing, pitting, and scratching. PE liners displayed all
      damage modes. Damage was exhibited on 93% of glenospheres and 100% of PE liners.
      Of 29 aseptic shoulders, 13 showed evidence of scapular notching and 5 of humeral
      loosening. There was a moderate correlation between radiographically observed
      implant failure or dissociation and PE embedding (r = 0.496; P < .001). There
      were weak and moderate correlations between scapular notching severity and PE
      dishing (r = 0.496; P = .006), embedding (r = 0.468; P = .010), and delamination
      (r = 0.384; P = .040). CONCLUSIONS: To date, this is the largest series of
      retrieved RTSA components and the first to relate damage modes to radiographic
      and clinical data. Most damage was observed on the PE liners, on both the
      articular surface and rim, and glenosphere components. Correlation of retrieval
      findings with radiographic and clinical data may help establish predictors of
      prostheses at risk for failure.

PMID- 26212757
TI  - Rap1 GTPase is required for mouse lens epithelial maintenance and morphogenesis.
AB  - Rap1, a Ras-like small GTPase, plays a crucial role in cell-matrix adhesive
      interactions, cell-cell junction formation, cell polarity and migration. The role
      of Rap1 in vertebrate organ development and tissue architecture, however, remains
      elusive. We addressed this question in a mouse lens model system using a
      conditional gene targeting approach. While individual germline deficiency of
      either Rap1a or Rap1b did not cause overt defects in mouse lens, conditional
      double deficiency (Rap1 cKO) prior to lens placode formation led to an ocular
      phenotype including microphthalmia and lens opacification in embryonic mice. The
      embryonic Rap1 cKO mouse lens exhibited striking defects including loss of E
      cadherin- and ZO-1-based cell-cell junctions, disruption of paxillin and beta1
      integrin-based cell adhesive interactions along with abnormalities in cell shape
      and apical-basal polarity of epithelium. These epithelial changes were
      accompanied by increased levels of alpha-smooth muscle actin, vimentin and N
      cadherin, and expression of transcriptional suppressors of E-cadherin (Snai1,
      Slug and Zeb2), and a mesenchymal metabolic protein (Dihydropyrimidine
      dehydrogenase). Additionally, while lens differentiation was not overtly
      affected, increased apoptosis and dysregulated cell cycle progression were noted
      in epithelium and fibers in Rap1 cKO mice. Collectively these observations
      uncover a requirement for Rap1 in maintenance of lens epithelial phenotype and
      morphogenesis. 

PMID- 26212761
TI  - Synthesis of mesoporous nanocomposites for their application in solid oxide
      electrolysers cells: microstructural and electrochemical characterization.
AB  - Fabrication routes for new SOEC mesoporous nanocomposite materials as electrodes
      are presented in this paper. NiO-CGO and SDC-SSC are described as possible new
      materials and their synthesis and the cell fabrication are discussed. The
      obtained materials are microstructurally characterised by SEM, TEM and XRD, where
      the mesoporous structures are observed and analysed. The obtained samples are
      electrochemically analysed by I-V polarisation curves and EIS analysis, showing a
      maximum current density of 330 mA cm(-2) at 1.7 V. A degradation of the cell
      performance is evidenced after a potentiostatic test at 1.4 V after more than 40
      hours. Oxygen electrode delaminating is detected, which is most probably the main
      cause of ageing. Even taking into account the lack of durability of the
      fabricated cells, the mesoporous electrodes do not seem to be altered, opening
      the possibility for further studies devoted to this high stability material for
      SOEC electrodes. 

PMID- 26212760
TI  - Medium-term natural history of subacromial impingement syndrome.
AB  - BACKGROUND: We evaluated the factors that affect the natural course of
      subacromial impingement syndrome in patients without rotator cuff tears. METHODS:
      In total, 63 patients were included. During the first evaluation, we recorded
      each patient's age, gender, profession, body mass index (BMI), hand dominance,
      alcohol and tobacco consumption, comorbidities, causative event of pain, presence
      of a functional limitation, duration of symptoms, shoulder scores (American
      Shoulder and Elbow Surgeons [ASES], Constant-Murley, and visual analog scale),
      history of subacromial steroid injections, and magnetic resonance imaging (MRI)
      classification. A subacromial lidocaine injection test was performed to confirm
      the diagnosis, and patients were initially treated conservatively. Of the 63
      patients, 7 underwent a subsequent surgical procedure. We recalled the patients
      and questioned them about recurrences. According to their answers, the patients
      were grouped as follows: group 1, no recurrence; group 2, relapsing course; and
      group 3, chronic course. We compared the groups regarding the factors proposed to
      affect the course of the disease. RESULTS: The mean follow-up time was 8.45 +/-
      0.9 years. There were no significant differences regarding gender, profession,
      hand dominance, alcohol consumption, smoking, comorbidities, causative event of
      pain, visual analog scale score, or history of subacromial steroid injections
      between groups. The patients in group 1 were significantly younger than those in
      group 2 (P = .038). The mean BMI value of the group 1 patients was significantly
      lower than that of the group 3 patients (P = .034). Patients with a functional
      limitation besides pain tended to have a relapsing course. The Constant-Murley
      and ASES scores were significantly higher for patients in group 1 than for
      patients in group 2 (P = .024 and P = .041, respectively). The duration of
      symptoms was significantly shorter (<3 months) in group 1 (P = .001). Most of the
      patients in group 1 had reversible changes on MRI (P = .038). CONCLUSION: In our
      study, younger age, lower BMI, more functional capacity, a shorter symptomatic
      period, reversible changes on MRI, and higher Constant and ASES scores at the
      first evaluation were good prognostic factors.

PMID- 26212762
TI  - Description of new species of Pterygorhabditis Timm, and Aspidonema (Sachs, )
      Andrassy, (Nematoda: Bunonematoidea) in aquatic habitats from India.
AB  - The paper contains descriptions of two new species of the genera Pterygorhabditis
      Timm, 1957 and Aspidonema (Sachs, 1949) Andrassy, 1958 belonging to the families
      Pterygorhabditidae Goodey 1963 and Bunonematidae Micoletzky 1922, respectively.
      Species were procured from fixed samples, collected earlier from aquatic
      habitats. Pterygorhabditis punctata n. sp. is characterized by a cuticle with
      flattened hexagonal blocks arranged in eight longitudinal rows in both sexes;
      each metastegostomal plate with a minute denticle, and males with long, slender,
      fused spicules and nine pairs of post-cloacal, prominently setose genital
      papillae. Aspidonema formosa n. sp. is the first report of the genus from India.
      The species is characterized by the right side provided with 35-48 pairs of warts
      flanking a row of smooth membranous shields and surrounded by a well-developed
      network and an anisomorphic metastegostom without discernible armature. Species
      are compared with other congeners, together with the diagnoses of amended genera,
      and keys to the identification of species are provided. 

PMID- 26212763
TI  - Prediction of drug-induced nephrotoxicity and injury mechanisms with human
      induced pluripotent stem cell-derived cells and machine learning methods.
AB  - The renal proximal tubule is a main target for drug-induced toxicity. The
      prediction of proximal tubular toxicity during drug development remains
      difficult. Any in vitro methods based on induced pluripotent stem cell-derived
      renal cells had not been developed, so far. Here, we developed a rapid 1-step
      protocol for the differentiation of human induced pluripotent stem cells (hiPSC)
      into proximal tubular-like cells. These proximal tubular-like cells had a purity
      of >90% after 8 days of differentiation and could be directly applied for
      compound screening. The nephrotoxicity prediction performance of the cells was
      determined by evaluating their responses to 30 compounds. The results were
      automatically determined using a machine learning algorithm called random forest.
      In this way, proximal tubular toxicity in humans could be predicted with 99.8%
      training accuracy and 87.0% test accuracy. Further, we studied the underlying
      mechanisms of injury and drug-induced cellular pathways in these hiPSC-derived
      renal cells, and the results were in agreement with human and animal data. Our
      methods will enable the development of personalized or disease-specific hiPSC
      based renal in vitro models for compound screening and nephrotoxicity prediction.

PMID- 26212764
TI  - Exciton Fine Structure of CdSe/CdS Nanocrystals Determined by Polarization
      Microscopy at Room Temperature.
AB  - We present a method that allows determining the band-edge exciton fine structure
      of CdSe/CdS dot-in-rods samples based on single particle polarization
      measurements at room temperature. We model the measured emission polarization of
      such single particles considering the fine structure properties, the dielectric
      effect induced by the anisotropic shell, and the measurement configuration. We
      use this method to characterize the band-edge exciton fine structure splitting of
      various samples of dot-in-rods. We show that, when the diameter of the CdSe core
      increases, a transition from a spherical like band-edge exciton symmetry to a rod
      like band edge exciton symmetry occurs. This explains the often reported large
      emission polarization of such particles compared to spherical CdSe/CdS emitters. 

PMID- 26212767
TI  - [D. Riethmuller in reply to the article by G. Bleu et al.: Assessment of vacuum
      assisted delivery in a Frank breech presentation. Gynecol Obstet Fertil
      2015;43:123-7].

PMID- 26212768
TI  - The age of the Lower Paleolithic occupation at Schoningen.
AB  - Thermoluminescence (TL) data are presented for eight samples of heated flint
      collected at the archaeological site of Schoningen 13/I-1 (Cycle I), for which a
      Holsteinian age is suggested by palynology of stratigraphically similar positions
      within a cyclic sedimentological model for the Quaternary sequence of Schoningen.
      Although the fire responsible for the zeroing of the TL-signal cannot be
      unequivocally attributed to human activities, any time difference between a
      natural fire and the human occupation is negligible for a site of this antiquity.
      The weighted mean age of 321 +/- 16 ka places the last heating of the flints
      nominally in the age range of Marine Isotope Stages (MIS) 10 to 8. By inference
      this data would suggest an attribution of the Holsteinian to MIS 9 and may also
      serve as a maximum age estimate for the spear site of Schoningen 13/II-4 (Cycle
      II). Considering the chronometric data available and following an alternative
      sedimentological model the age of these two sites at Schoningen can be considered
      as belonging to the same climatic cycle. This suggests an attribution to MIS 9,
      and by inference provides an age estimate of 337-300 ka for the oldest spears in
      human history.

PMID- 26212769
TI  - Quantitative targeted and retrospective data analysis of relevant pesticides,
      antibiotics and mycotoxins in bakery products by liquid chromatography-single
      stage Orbitrap mass spectrometry.
AB  - In addition to 'traditional' multi-residue and multi-contaminant multiple
      reaction monitoring (MRM) mass spectrometric techniques devoted to quantifying a
      list of targeted compounds, the global food industry requires non-targeted
      methods capable of detecting other possible potentially hazardous compounds.
      Ultra-high-performance liquid chromatography combined with a single-stage
      Orbitrap high-resolution mass spectrometer (UHPLC-HRMS ExactiveTM-Orbitrap
      Technology) was successfully exploited for the complete selective and
      quantitative determination of 33 target compounds within three major cross
      categories (pesticides, antibiotics and mycotoxins) in bakery matrices
      (specifically milk, wheat flour and mini-cakes). Resolution was set at 50 000
      full width at half maximum (FWHM) to achieve the right compromise between an
      adequate scan speed and selectivity, allowing for the limitations related to the
      necessary generic sample preparation approach. An exact mass with tolerance of 5
      ppm and minimum peak threshold of 10 000 units were fixed as the main
      identification conditions, including retention time and isotopic pattern as
      additional criteria devoted to greatly reducing the risk of false-positive
      findings. The full validation for all the target analytes was performed:
      linearity, intermediate repeatability and recovery (28 analytes within 70-120%)
      were positively assessed; furthermore, limits of quantification between 5 and 100
      ug kg(-1) (with most of the analytes having a limit of detection below 6 ug kg(
      1)) indicate good performance, which is compatible with almost all the regulatory
      needs. Naturally contaminated and fortified mini-cakes, prepared through combined
      use of industrial and pilot plant production lines, were analysed at two
      different concentration levels, obtaining good overall quantitative results and
      providing preliminary indications of the potential of full-scan HRMS cluster
      analysis. The effectiveness of this analytical approach was also tested in terms
      of the formulation of hypotheses for the identification of other analytes not
      initially targeted which can have toxicological implications (e.g. 3-acetyl
      deoxynivalenol and deoxynivalenol-3-glucoside), opening a window on retrospective
      investigation perspectives in food safety laboratories.

PMID- 26212770
TI  - CdSe quantum dots and N719-dye decorated hierarchical TiO2 nanorods for the
      construction of efficient co-sensitized solar cells.
AB  - Three-dimensional hierarchical TiO2 nanorods (HTNs) decorated with the N719 dye
      and 3-mercaptopropionic or oleic acid capped CdSe quantum dots (QDs) in
      photoanodes for the construction of TiO2 nanorod-based efficient co-sensitized
      solar cells are reported. These HTN co-sensitized solar cells showed a maximum
      power-conversion efficiency of 3.93 %, and a higher open-circuit voltage and fill
      factor for the photoanode with 3-mercaptopropionic acid capped CdSe QDs due to
      the strong electronic interactions between CdSe QDs, N719 dye and HTNs, and the
      superior light-harvesting features of the HTNs. An electrochemical impedance
      analysis indicated that the superior charge-collection efficiency and electron
      diffusion length of the CdSe QD-coated HTNs improved the photovoltaic performance
      of these HTN co-sensitized solar cells. 

PMID- 26212771
TI  - Changes in breastfeeding and nutritional status of Nigerian children between 1990
      and 2008, and variations by region, area of residence and maternal education and
      occupation.
AB  - BACKGROUND: Inadequate breastfeeding practices contribute to malnutrition in
      young children. AIMS AND OBJECTIVES: This study examined changes in breastfeeding
      practices and the nutritional status of children (0-35 months, n = 37154) using
      data from the nationally-representative Nigerian Demographic and Health Surveys
      for 1990-2008. METHODS: The study estimated the relative changes in the
      proportion of children meeting recommended breastfeeding practices and the
      anthropometric indices of the children during the study period, by region, place
      of residence, maternal education and maternal occupation. RESULTS: In each study
      year, over 97% of the children were ever breastfed. The proportion of infants
      breastfed within 1 hour and 1 day of birth increased from 34% to 45.8%, and from
      63.8% to 82.3%, respectively. Overall, breastfeeding for >= 12 months changed
      from 88.9% to 95.2%, an increase of 7%; however, an increase of 14% was observed
      in the northern region (from 86.1% to 97.8%) while a decline of 7% was observed
      in the southern region (from 97.1% to 89.9%). Over the study period, the
      prevalence of all the assessed indicators of malnutrition (stunting, wasting and
      underweight) increased in the northern region while the southern region
      experienced a decline in all except severe wasting. In both urban and rural
      areas, stunting and wasting increased, while underweight declined. Children of
      non-formally educated and unemployed mothers were more malnourished in all the
      study years. CONCLUSION: Improvement in some breastfeeding practices did not
      result in improvement in the nutritional status of Nigerian children during 1990
      2008, particularly in northern Nigeria and among socially disadvantaged mothers.
      Improving maternal education and employment, and integrating messages on
      techniques and benefits of optimal infant feeding with other maternal and child
      healthcare services could be beneficial.

PMID- 26212772
TI  - Risk of Pulmonary Embolism and Deep Venous Thrombosis in Systemic Sclerosis: A
      General Population-Based Study.
AB  - OBJECTIVE: To determine the risk of venous thromboembolism (VTE) (pulmonary
      embolism [PE] and deep vein thrombosis [DVT]) in individuals with incident
      systemic sclerosis (SSc; scleroderma) in the general population. METHODS: Using a
      population database that includes all residents of British Columbia, Canada, we
      conducted a cohort study of all patients with incident SSc and up to 10 age-, sex
      , and entry time-matched individuals from the general population. We compared
      incidence rates of PE, DVT, and VTE between the 2 groups according to SSc disease
      duration. We calculated hazard ratios (HRs), adjusting for confounders. RESULTS:
      Among 1,245 individuals with SSc (83% female, mean age 56 years), the incidence
      rates of PE, DVT, and VTE were 3.47, 3.48, and 6.56 per 1,000 person-years,
      respectively, whereas the corresponding rates were 0.78, 0.76, and 1.37 per 1,000
      person-years among 12,670 non-SSc individuals. Compared with non-SSc individuals,
      the multivariable HRs among SSc patients were 3.73 (95% confidence interval [95%
      CI] 1.98-7.04), 2.96 (95% CI 1.54-5.69), and 3.47 (95% CI 2.14-5.64) for PE, DVT,
      and VTE, respectively. The age-, sex-, and entry time-matched HRs for PE, DVT,
      and VTE were highest during the first year after SSc diagnosis (32.77 [95% CI
      6.60-162.75], 8.50 [95% CI 3.13-23.04], and 12.03 [95% CI 5.27-27.45],
      respectively). CONCLUSION: These findings provide population-based evidence that
      SSc patients are at a substantially increased risk of VTE, especially within the
      first year after SSc diagnosis. Increased monitoring for this potentially fatal
      outcome and its modifiable risk factors is warranted in this patient population.

PMID- 26212773
TI  - Frequency and Indications of Parenteral Nutrition in an Acute Palliative Care
      Unit.
AB  - The aim of this study was to estimate the use of parenteral nutrition (PN) in
      advanced cancer patients enrolled in an acute pain relief and palliative care
      unit of a comprehensive cancer center and the appropriateness of the criteria to
      select patients for PN. Fourteen out of 750 patients (1.8%) admitted to an acute
      palliative care unit were administered PN. Patients were referred from various
      settings. The mean age was 58 yr (range 37-79), and 9 were males. The mean
      hospital stay was 7.7 days (range 3-14), and the mean Karnofsky level was 35
      (range 10-50). The principal indication was bowel obstruction. Ten patients (71%)
      were already receiving PN before admission, and 2 of them discontinued the
      treatment during admission. Four patients (29%) started PN during hospital
      admission as decided by the staff. Twelve patients (85%) were discharged on PN.
      One week after hospital discharge, 9 patients were still receiving PN, 4 patients
      died, and no data were available for 1 patient. One month after hospital
      discharge only 2 patients of these were still on PN, 2 patients discontinued PN,
      and 5 patients died. This study shows that decisions to start or to stop PN were
      individually based on multiple considerations, not only clinical. Goals may vary
      from expected clinical benefits to compassionate use. The administration of PN
      should be assessed carefully and individually approached.

PMID- 26212774
TI  - Benzo[c,d]indole-Containing Aza-BODIPY Dyes: Asymmetrization-Induced Solid-State
      Emission and Aggregation-Induced Emission Enhancement as New Properties of a Well
      Known Chromophore.
AB  - A series of symmetric and asymmetric benzo[c,d]indole-containing aza boron
      dipyrromethene (aza-BODIPY) compounds was synthesized by a titanium tetrachloride
      mediated Schiff-base formation reaction of commercially available
      benzo[c,d]indole-2(1H)-one and heteroaromatic amines. These aza-BODIPY analogues
      show different electronic structures from those of regular aza-BODIPYs, with
      hypsochromic shifts of the main absorption compared to their BODIPY counterparts.
      In addition to the intense fluorescence in solution, asymmetric compounds
      exhibited solid-state fluorescence due to significant contribution of the
      vibronic bands to both absorption and fluorescence as well as reduced
      fluorescence quenching in the aggregates. Finally, aggregation-induced emission
      enhancement, which is rare in BODIPY chromophores, was achieved by introducing a
      nonconjugated moiety into the core structure. 

PMID- 26212775
TI  - Discovery of tripeptide-derived multifunctional ligands possessing delta/mu
      opioid receptor agonist and neurokinin 1 receptor antagonist activities.
AB  - Several bifunctional peptides were synthesized and characterized based on the
      pentapeptide-derived ligand NP30 (1: Tyr-DAla-Gly-Phe-Gly-Trp-O-[3',5'
      Bzl(CF3)2]). Modification and truncation of amino acid residues were performed,
      and the tripeptide-derived ligand NP66 (11: Dmt-DAla-Trp-NH-[3',5'-(CF3)2-Bzl])
      was obtained based on the overlapping pharmacophore concept. The Trp(3) residue
      of ligand 11 works as a message residue for both opioid and NK1 activities. The
      significance lies in the observation that the approach of appropriate truncation
      of peptide sequence could lead to a tripeptide-derived chimeric ligand with
      effective binding and functional activities for both mu and delta opioid and NK1
      receptors with agonist activities at mu and delta opioid and antagonist activity
      at NK1 receptors, respectively. 

PMID- 26212776
TI  - Discovery of novel triazolobenzazepinones as gamma-secretase modulators with
      central Abeta42 lowering in rodents and rhesus monkeys.
AB  - Synthesis and SAR studies of novel triazolobenzazepinones as gamma secretase
      modulators (GSMs) are presented in this communication. Starting from our
      azepinone leads, optimization studies toward improving central lowering of
      Abeta42 led to the discovery of novel benzo-fused azepinones. Several
      benzazepinones were profiled in vivo and found to lower brain Abeta42 levels in
      Sprague Dawley rats and transgenic APP-YAC mice in a dose-dependent manner after
      a single oral dose. Compound 34 was further progressed into a pilot study in our
      cisterna-magna-ported rhesus monkey model, where we observed robust lowering of
      CSF Abeta42 levels. 

PMID- 26212777
TI  - Discovery of new acetylcholinesterase inhibitors with small core structures
      through shape-based virtual screening.
AB  - Targeting acetylcholinesterase (AChE) using small molecule inhibitors is
      considered to be the most successful therapeutic strategy in the treatment of
      Alzheimer's disease (AD). Herein we present a shape-based virtual screening to
      identify new cores for the designing of AChE inhibitors. Ten active hits are
      identified and the most active hit, 5169-0032 and T5369186, showed comparable
      AChE inhibitory activity to tacrine. Prediction of physicochemical properties and
      ADME/T risk indicates their potential in druggability and safety. The two
      compounds provide new core and can serve as a promising fragment to design potent
      AChE inhibitors. 

PMID- 26212778
TI  - Correlation of histomorphological pattern of cardiac amyloid deposition with
      amyloid type: a histological and proteomic analysis of 108 cases.
AB  - AIMS: Prognostication and treatment selection for cardiac amyloidosis requires
      accurate amyloid typing. The aim of this study was to investigate the utility of
      histomorphology for predicting type. METHODS AND RESULTS: Autopsy cases with
      cardiac amyloidosis (1998-2010) were typed by the use of mass spectrometry-based
      proteomics. Deposition patterns were correlated with amyloid type. Among 108
      decedents (mean age 75 years; 69% men), 107 had a single type, including
      transthyretin (ATTR) (60 cases), amyloid light chain (AL) (32 lambda; 12 kappa),
      amyloid A (AA) (two), and apolipoprotein AIV (AApoAIV) (one). Interstitial
      deposition was more extensive in AL amyloidosis cases than in ATTR cases [odds
      ratio (OR) 6.8, P = 0.0004]. Histomorphological patterns of interstitial
      deposition were mixed in 61% of AL amyloidosis cases and in 61% of ATTR cases,
      but diffuse pericellular deposits favoured AL amyloidosis (OR 10.7, P = 0.0001),
      nodular deposits favoured ATTR (OR 3.1, P = 0.0229), and discrete pericellular
      deposits tended to partially favour ATTR (OR 1.7, P = 0.1970). Arterial and
      venous deposits each favoured AL amyloidosis (OR ranging from 9.3 to 192.0, P
      value ranging from 0.0022 to <0.0001), and were severe in AL amyloidosis.
      Endocardial deposits favoured AL amyloidosis (OR 46.3, P < 0.0001) and were also
      more severe in AL amyloidosis. CONCLUSIONS: The extent and distribution of
      cardiac amyloidosis strongly correlate with amyloid type, suggesting fundamental
      differences in the pathobiology of deposition. The tendency for mixed patterns to
      occur limits the practicality and accuracy of using histopathology for amyloid
      typing.

PMID- 26212779
TI  - Comparison of Four Saliva Detection Methods to Identify Expectorated Blood
      Spatter.
AB  - Blood spatter analysis is an important step for crime scene reconstruction. The
      presence of saliva in blood spatter could indicate expectorated blood which is
      difficult to distinguish from impact spatter. In this study, four saliva test
      methods (SALIgAE((r)) , Phadebas((r)) sheet, RSID(TM) -Saliva kit, and starch gel
      diffusion) were compared to identify the best method for detecting expectorated
      blood spatter. The RSID(TM) -Saliva kit showed the highest sensitivity even when
      saliva was mixed with blood, and was not inhibited by the presence of blood. The
      SALIgAE((r)) test provided easy and rapid results, but the yellow color of a
      positive reaction was overwhelmed by the red color of the blood. The starch gel
      diffusion method and the Phadebas((r)) sheet exhibited relatively low sensitivity
      and the assay took a long time. When using the RSID(TM) -Saliva kit for
      identifying saliva in blood, results should be read within 10 min.

PMID- 26212781
TI  - Report of the International Journal of Urology Editorial Board Meeting 2015 in
      Kanazawa, Japan.

PMID- 26212782
TI  - Aroma volatiles obtained at harvest by HS-SPME/GC-MS and INDEX/MS-E-nose
      fingerprint discriminate climacteric behaviour in melon fruit.
AB  - BACKGROUND: Melon aroma volatiles were extracted at harvest from juice of a
      climacteric near-isogenic line (NIL) SC3-5-1 with two quantitative trait loci
      (QTLs) introgressed which produced climacteric behaviour and its non-climacteric
      parental (PS) using two methodologies of analysis: static headspace solid phase
      micro-extraction (HS-SPME) by gas chromatography-mass spectrometry (GC-MS) and
      inside needle dynamic extraction (INDEX) by MS-based electronic nose (MS-E-nose).
      RESULTS: Of the 137 volatiles compounds identified, most were found at
      significantly higher concentrations in SC3-5-1 than in PS in both seasons. These
      volatiles were mostly esters, alcohols, sulfur-derived esters and even some
      aldehydes and others. The number of variables with high correlation values was
      reduced by using correlation network analysis. Partial least squares-discriminant
      analysis (PLS-DA) achieved the correct classification of PS and SC3-5-1. The ions
      m/z 74, 91, 104, 105, 106 and 108, mainly volatile derivatives precursor
      phenylalanine, were the most discriminant in SC3-5-1 and PS. As many as 104 QTLs
      were mapped in season 1 and at least 78 QTLs in each season with an effect above
      the PS mean. CONCLUSION: GC-MS gave better discrimination than E-nose. Most of
      the QTLs that mapped in both seasons enhanced aroma volatiles associated with
      climacteric behaviour.

PMID- 26212783
TI  - Spatial and Temporal Dimensions of Urban Expansion in China.
AB  - The scale of urbanization in China during the past three decades is unprecedented
      in human history, and the processes are poorly understood. Here we present an
      effort to map the urban land expansion processes of 32 major cities in China from
      1978 to 2010 using Landsat satellite data to understand the temporal and spatial
      characteristics. Results showed that the urban extent of the 32 cities expanded
      exponentially with very high annual rates varying from 3.2% to 12.8%. Temporal
      fluctuation in urban expansion rates in these 32 cities was obvious, with
      unexpected and alarming expansion rates from 2005 to 2010 that drastically
      exceeded their expectation, which was calculated from the long-term trend between
      1978 and 2005, by 45%. Overall, we found that the growth rates of cities during
      the entire study period were inversely related to city size, contradicting the
      theory or Gibrat's law, which states that the growth rate is independent of city
      size. More detailed analysis indicated that city growth in China has transitioned
      from contradicting to conforming to Gibrat's law since 1995. Our study suggests
      that the urban expansion theory (i.e., Gibrat's law) does not fit Chinese
      expansion consistently over time, and the exact causes are unknown. Exploring the
      causes in future research will improve our understanding of the theory and, more
      importantly, understand the feasibility of the theoretical relationship between
      city size and expansion rate in guiding contemporary urban expansion planning.

PMID- 26212784
TI  - Numerical investigation of nanoparticles transport in anisotropic porous media.
AB  - In this work the problem related to the transport of nanoparticles in anisotropic
      porous media is investigated numerically using the multipoint flux approximation.
      Anisotropy of porous media properties is an essential feature that exists almost
      everywhere in subsurface formations. In anisotropic media, the flux and the
      pressure gradient vectors are no longer collinear and therefore interesting
      patterns emerge. The transport of nanoparticles in subsurface formations is
      affected by several complex processes including surface charges, heterogeneity of
      nanoparticles and soil grain collectors, interfacial dynamics of double-layer and
      many others. We use the framework of the theory of filtration in this
      investigation. Processes like particles deposition, entrapment, as well as
      detachment are accounted for. From the numerical methods point of view,
      traditional two-point flux finite difference approximation cannot handle
      anisotropy of media properties. Therefore, in this work we use the multipoint
      flux approximation (MPFA). In this technique, the flux components are affected by
      more neighboring points as opposed to the mere two points that are usually used
      in traditional finite volume methods. We also use the experimenting pressure
      field approach which automatically constructs the global system of equations by
      solving multitude of local problems. This approach facilitates to a large extent
      the construction of the global system. A set of numerical examples is considered
      involving two-dimensional rectangular domain. A source of nanoparticles is
      inserted in the middle of the anisotropic layer. We investigate the effects of
      both anisotropy angle and anisotropy ratio on the transport of nanoparticles in
      saturated porous media. It is found that the concentration plume and porosity
      contours follow closely the principal direction of anisotropy of permeability of
      the central domain. 

PMID- 26212785
TI  - Long-circulating self-assembled cholesteryl albumin nanoparticles enhance tumor
      accumulation of hydrophobic anticancer drug.
AB  - The objective of this study was to develop an albumin nanoparticle with improved
      stability and drug loading capacity. Generation of nanomaterials having
      physiologically stable and high potential for drug delivery is still challenging.
      Herein we synthesized cholesteryl albumin conjugate using N,N-disuccinimidyl
      carbonate coupling reagent and prepared paclitaxel-loaded cholesteryl albumin
      nanoparticle (PTX-Chol-BSA) by self-assembly with the mean hydrodynamic diameter
      of 147.6+/-1.6nm and with high loading capacity. PTX-Chol-BSA nanoparticle showed
      much higher colloidal stability than a simple complex of PTX and BSA (PTX-BSA)
      and sustained release profile. PTX-Chol-BSA nanoparticles exhibited greater
      cellular uptake and cytotoxicity in B16F10 and MCF-7 cancer cell lines, as
      compared with PTX in Cremophor EL/ethanol (PTX-Cre/EtOH) and PTX-BSA
      formulations. A pharmacokinetic study in tumor-bearing mice showed that the area
      under the concentration-time curve (AUC0-8 h) following the administration of PTX
      Chol-BSA was 1.6-2-fold higher than those following the administration of PTX
      Cre/EtOH and PTX-BSA. In addition, the tumor AUC0-8 h of PTX-Chol-BSA was around
      2-fold higher than that of PTX-BSA. Furthermore, in vivo antitumor efficacy
      results revealed that PTX-Chol-BSA nanoparticles have greater antitumor efficacy.
      In conclusion, we demonstrated the potential of PTX-Chol-BSA nanoparticles for
      anti-tumor chemotherapy, with enhanced in vitro and in vivo behaviors, as
      compared to PTX-BSA and PTX-Cre/EtOH. 

PMID- 26212786
TI  - How relevant are assembled equilibrium samples in understanding structure
      formation during lipid digestion?
AB  - Lipid-based formulations are gaining interest for use as drug delivery systems
      for poorly water-soluble drug compounds. During digestion, the lipolysis products
      self-assemble with endogenous surfactants in the gastrointestinal tract to form
      colloidal structures, enabling enhanced drug solubilisation. Although earlier
      studies in the literature focus on assembled equilibrium systems, little is known
      about structure formation under dynamic lipolysis conditions. The purpose of this
      study was to investigate the likely colloidal structure formation in the small
      intestine after the ingestion of lipids, under equilibrium and dynamic
      conditions. The structural aspects were studied using small angle X-ray
      scattering and dynamic light scattering, and were found to depend on lipid
      composition, lipid chain length, prandial state and emulsification. Incorporation
      of phospholipids and lipolysis products into bile salt micelles resulted in
      swelling of the structure. At insufficient bile salt concentrations, a co
      existing lamellar phase was observed, due to a reduction in the solubilisation
      capacity for lipolysis products. Emulsification accelerated the rate of lipolysis
      and structure formation. 

PMID- 26212788
TI  - Shades of gray mouse lemurs: Ontogeny of female dominance and dominance-related
      behaviors in a nocturnal primate.
AB  - The ontogeny and establishment of dominance relationships in young individuals
      have been investigated in various group-living, diurnal primates but respective
      information is almost entirely lacking for nocturnal, non-gregarious species. As
      in many other mammals male primates often represent the dominant sex, but the
      opposite phenomenon (female dominance) is particularly frequent in lemurs,
      although almost nothing is known about its development. Therefore, we
      investigated the development of intersexual dominance in parallel to age-related
      changes in other relevant behaviors in the gray mouse lemur, a solitary forager
      with female dominance. In particular, the temporal trajectories of social play,
      marking behavior, social tolerance, and agonistic behaviors were characterized in
      captive dyads of three different age categories (ACs), among juveniles (ACI: 4-5
      months, N = 6), adolescents (ACII: 8-9 months, N = 8) and young adults (ACIII: 12
      13 months, N = 8). Data were collected during a series of three encounter
      experiments between one male and one female per dyad and age category (total
      observation time: 49.5 hr). Play behavior was observed in all age classes,
      although the number of playing dyads decreased with increasing age. A significant
      age-dependent increase in marking behavior was found in females, especially in
      substrate rubbing and urine washing, but not in males. Although conflict rates
      did not differ significantly between ACs, females started to win more conflicts
      from ACII onwards, and social tolerance decreased partly with increasing age.
      Clear dominance relationships were not observed in ACI and first indications of
      dominant females were found in ACII with an increasing number in ACIII. This
      study provides first information about the ontogeny of female dominance in a
      nocturnal primate and shows that this behavior develops relatively late during
      ontogeny. In conclusion, this study provides evidence for significant changes in
      the social lives of maturing mouse lemurs and a rather late social maturation in
      this species.

PMID- 26212787
TI  - Drivers of temporal changes in temperate forest plant diversity vary across
      spatial scales.
AB  - Global biodiversity is affected by numerous environmental drivers. Yet, the
      extent to which global environmental changes contribute to changes in local
      diversity is poorly understood. We investigated biodiversity changes in a meta
      analysis of 39 resurvey studies in European temperate forests (3988 vegetation
      records in total, 17-75 years between the two surveys) by assessing the
      importance of (i) coarse-resolution (i.e., among sites) vs. fine-resolution
      (i.e., within sites) environmental differences and (ii) changing environmental
      conditions between surveys. Our results clarify the mechanisms underlying the
      direction and magnitude of local-scale biodiversity changes. While not detecting
      any net local diversity loss, we observed considerable among-site variation,
      partly explained by temporal changes in light availability (a local driver) and
      density of large herbivores (a regional driver). Furthermore, strong evidence was
      found that presurvey levels of nitrogen deposition determined subsequent
      diversity changes. We conclude that models forecasting future biodiversity
      changes should consider coarse-resolution environmental changes, account for
      differences in baseline environmental conditions and for local changes in fine
      resolution environmental conditions. 

PMID- 26212789
TI  - Chaperone-mediated autophagy prevents apoptosis by degrading BBC3/PUMA.
AB  - Autophagy is a potentially inimical pathway and together with apoptosis, may be
      activated by similar stress stimuli that can lead to cell death. The molecular
      cues that dictate the cell fate choice between autophagy and apoptosis remain
      largely unknown. Here we report that the proapoptotic protein BBC3/PUMA (BCL2
      binding component 3) is a bona fide substrate of chaperone-mediated autophagy
      (CMA). BBC3 associates with HSPA8/HSC70 (heat shock 70kDa protein 8), leading to
      its lysosome translocation and uptake. Inhibition of CMA results in stabilization
      of BBC3, which in turn sensitizes tumor cells to undergo apoptosis. We further
      demonstrate that upon TNF (tumor necrosis factor) treatment, IKBKB/IKKbeta
      (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta)
      mediated BBC3 Ser10 phosphorylation is crucial for BBC3 stabilization via
      blocking its degradation by CMA. Mechanistically, Ser10 phosphorylation
      facilitates BBC3 translocation from the cytosol to mitochondria. BBC3
      stabilization resulting from either Ser10 phosphorylation or CMA inhibition
      potentiates TNF-induced apoptotic cell death. Our findings thus reveal that the
      selective degradation of BBC3 underlies the prosurvival role of CMA and define a
      previously unappreciated proapoptotic role of IKBKB that acts through
      phosphorylation-mediated stabilization of BBC3, thereby promoting TNF-triggered
      apoptosis. 

PMID- 26212791
TI  - Oscillatory responses to reward processing in borderline personality disorder.
AB  - OBJECTIVES: Previous electrophysiological studies have confirmed impaired reward
      processing in patients with BPD. However, it is not clear which aspects of reward
      processing are affected and which brain regions are involved. The present study
      investigated both evoked and induced event-related oscillations (EROs) to
      feedback events (thought to represent different aspects of feedback processing),
      and used source localization (sLORETA) to assess activity in two areas known to
      contribute to reward processing, the dorsomedial prefrontal/anterior cingulate
      cortex (dmPFC/ACC) and the orbitofrontal cortex (OFC). METHODS: Eighteen patients
      with BPD and 22 healthy controls performed a gambling task, while 64-channel
      electroencephalographic activity was recorded. Evoked and induced theta and high
      beta band EROs as well as activity in the two regions of interest were
      investigated depending on the valence and magnitude of feedback events. RESULTS:
      Theta-band responses to negative feedback were reduced in BPD, an effect that
      involved only evoked responses and the dmPFC/ ACC region, and was associated with
      trait impulsivity in patients. sLORETA analyses revealed disturbed evoked
      responses depending on feedback magnitude in the theta (OFC) and high-beta
      (dmPFC/ACC and OFC) frequency range. CONCLUSIONS: The results indicate multiple
      dysfunctions of feedback processing in patients with BPD, implicating several
      distinct subsets of reward-processing mechanisms.

PMID- 26212792
TI  - High predictive value of immune-inflammatory biomarkers for schizophrenia
      diagnosis and association with treatment resistance.
AB  - OBJECTIVES: Recent schizophrenia (SCZ) research aims to establish biomarkers with
      high predictive value for the diagnosis, severity of illness or treatment
      resistance. SCZ is accompanied by activated immune-inflammatory pathways,
      including increased levels of cytokines and chemokines, but few studies tried to
      identify predictive properties of such measures. METHODS: We included 54
      medicated SCZ patients and 118 healthy controls and examined 15 cytokines and
      chemokines. Possible associations between these immune-inflammatory biomarkers
      and the diagnosis of SCZ, severity of illness and treatment resistance were
      investigated. RESULTS: SCZ is associated with a specific cytokine - chemokine
      profile, i.e., increased CCL11, MIP-1alpha, sTNF-R1 and sTNF-R2 levels, and
      decreased levels of IP-10, TNF-alpha, IL-2 and IL-4. The combination of five
      biomarkers (sTNF-R1, sTNF-R2, CCL11, IP-10, IL-4) may predict the diagnosis of
      SCZ with a sensitivity of 70.0% and a specificity of 89.4%. There was a weak
      association between the negative symptoms and biomarkers, i.e., IL-2 (inversely)
      and CCL11 (positively). Patients with treatment resistance showed increased
      levels of sTNF-R1, sTNF-R2 and MCP-1. CONCLUSIONS: The findings of this study
      reinforce that SCZ is associated with a pro-inflammatory profile and suggest that
      some immune mediators may be used as reliable biomarkers for the diagnosis of SCZ
      and treatment resistance.

PMID- 26212790
TI  - Basolateral amygdala rapid glutamate release encodes an outcome-specific
      representation vital for reward-predictive cues to selectively invigorate reward
      seeking actions.
AB  - Environmental stimuli have the ability to generate specific representations of
      the rewards they predict and in so doing alter the selection and performance of
      reward-seeking actions. The basolateral amygdala participates in this process,
      but precisely how is unknown. To rectify this, we monitored, in near-real time,
      basolateral amygdala glutamate concentration changes during a test of the ability
      of reward-predictive cues to influence reward-seeking actions (Pavlovian
      instrumental transfer). Glutamate concentration was found to be transiently
      elevated around instrumental reward seeking. During the Pavlovian-instrumental
      transfer test these glutamate transients were time-locked to and correlated with
      only those actions invigorated by outcome-specific motivational information
      provided by the reward-predictive stimulus (i.e., actions earning the same
      specific outcome as predicted by the presented CS). In addition, basolateral
      amygdala AMPA, but not NMDA glutamate receptor inactivation abolished the
      selective excitatory influence of reward-predictive cues over reward seeking.
      These data support [corrected] the hypothesis that transient glutamate release in
      the BLA can encode the outcome-specific motivational information provided by
      reward-predictive stimuli.

PMID- 26212793
TI  - NGAL and other markers of inflammation as competitive or complementary markers
      for depressive symptom dimensions in heart failure.
AB  - OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory
      marker associated with the pathophysiology of heart failure (HF), the
      psychopathology of depression and the co-existing symptoms of depression in HF
      patients. The aim of this study is to determine whether the association of serum
      NGAL levels with depressive symptoms dimensions in HF is independent of well
      known inflammatory markers. METHODS: Serum NGAL, high sensitive C-reactive
      protein (hsCRP), tumour necrosis factor-alpha (TNF-alpha), its two soluble
      receptors; sTNFR1, sTNFR2, Interleukin-6 (IL-6) and leukocytes were measured in
      104 patients with HF at baseline and 12 months. Depressive symptoms were
      evaluated using the Beck Depression Inventory (BDI) at both timepoints.
      Correlations between NGAL and inflammatory markers and depressive symptoms
      dimensions were determined. The effect of hsCRP, IL-6, TNF-alpha, sTNFR1, sTNFR2
      and leukocytes on the association of NGAL with depressive symptoms was determined
      and adjusted for time, demographics, cardiac disease severity, and kidney
      function. RESULTS: NGAL levels were significantly correlated with hsCRP, TNF
      alpha, sTNFR1, sTNFR2 and leukocytes. NGAL was significantly associated with
      somatic depressive symptoms, independent of abovementioned markers. CONCLUSIONS:
      Serum NGAL is an independent inflammatory marker for somatic depressive symptoms
      in HF and may function as an immunopathogen linking somatic symptoms of
      depression to HF.

PMID- 26212794
TI  - Controllable Chemoselectivity in Visible-Light Photoredox Catalysis: Four Diverse
      Aerobic Radical Cascade Reactions.
AB  - Reported is the controllable selectivity syntheses of four distinct products from
      the same starting materials by visible-light photoredox catalysis. By employing a
      dicyanopyrazine-derived chromophore (DPZ) as photoredox catalyst, an aerobic
      radical mechanism has been developed, and allows the reactions of N
      tetrahydroisoquinolines (THIQs) with N-itaconimides to through four different
      pathways, including addition-cyclization, addition-elimination, addition
      coupling, and addition-protonation, with satisfactory chemoselectivity. The
      current strategy provide straightforward access to four different but valuable N
      heterocyclic adducts in moderate to excellent yields. 

PMID- 26212795
TI  - Participation in sport and physical activity in head and neck cancer survivors:
      associations with quality of life.
AB  - BACKGROUND: Head and neck cancer (HNC), and its treatment, is associated with
      significant side-effects which can affect quality of life (QOL). Physical
      activity (PA) is known to improve a number of QOL measures. We aimed to determine
      the prevalence of PA pre- and post-treatment of HNC and to determine associations
      with QOL. METHODS: A questionnaire-based survey of 172 patients pre- and post
      treatment for HNC. RESULTS: A total of 62.2% of patients met current UK PA
      guidelines pre-treatment, reducing to 40.1% following treatment. There was a
      significant decrease in Metabolic equivalent task minutes/week post-treatment,
      with 71% of participants reporting less PA after diagnosis (P < 0.001). Swimming
      and cycling remained the two most practiced sports. There was a positive
      correlation between the post-treatment PA and QOL (P < 0.001). CONCLUSION: These
      data suggest that PA may improve QOL following treatment for HNC. We believe that
      further studies are warranted.

PMID- 26212796
TI  - Coupling Mo2 C with Nitrogen-Rich Nanocarbon Leads to Efficient Hydrogen
      Evolution Electrocatalytic Sites.
AB  - In our efforts to obtain electrocatalysts with improved activity for water
      splitting, meticulous design and synthesis of the active sites of the
      electrocatalysts and deciphering how exactly they catalyze the reaction are
      vitally necessary. Herein, we report a one-step facile synthesis of a novel
      precious-metal-free hydrogen-evolution nanoelectrocatalyst, dubbed Mo2 C@NC that
      is composed of ultrasmall molybdenum carbide (Mo2 C) nanoparticles embedded
      within nitrogen-rich carbon (NC) nanolayers. The Mo2 C@NC hybrid
      nanoelectrocatalyst shows remarkable catalytic activity, has great durability,
      and gives about 100 % Faradaic yield toward the hydrogen-evolution reaction (HER)
      over a wide pH range (pH 0-14). Theoretical calculations show that the Mo2 C and
      N dopants in the material synergistically co-activate adjacent C atoms on the
      carbon nanolayers, creating superactive nonmetallic catalytic sites for HER that
      are more active than those in the constituents. 

PMID- 26212797
TI  - Pathological role of fibroblast-like synoviocytes in charcot neuroarthropathy.
AB  - This study was designed to characterize the synovium in the joints of Charcot
      neuroarthropathy (CNA) and investigate the potential role of fibroblast-like
      synoviocytes (FLS) in the pathology of CNA. Synovial samples were collected from
      CNA patients (n = 7) and non-CNA patients (n = 7), for control, during
      orthopaedic procedures and used for histology and isolation of FLS. Histological
      characterization of synovium included innervation and FLS localization. The
      isolated FLS from the CNA and non-CNA synovium were cultured, with or without
      tumor necrosis factor-alpha (TNF-alpha), for evaluation of invasiveness, gene
      expression, and cartilage degradation. Vasoactive intestinal peptide (VIP), a
      neuropeptide, was supplemented into the co-cultures of FLS and cartilage
      explants. Compared with the non-CNA synovium, CNA synovium was highly
      inflammatory, with reduced innervation and intense expression of cadherin-11. The
      FLS isolated from CNA synovium, particularly when activated with TNF-alpha, were
      more invasive, increased the expression of ADAMTS4, IL-6, and RANKL, and depleted
      proteoglycans from cartilage explants when they were co-cultured. Addition of VIP
      into the culture medium neutralized the catabolic effect of the CNA FLS on
      cartilage explants. In conclusion, FLS plays an important role in the pathology
      of CNA. Therapies targeting synovium and FLS may prevent or treat the joint
      destruction in CNA.

PMID- 26212798
TI  - Hepatocyte cell therapy in liver disease.
AB  - Liver disease is a leading cause of morbidity and mortality. Liver
      transplantation remains the only proven treatment for end-stage liver failure but
      is limited by the availability of donor organs. Hepatocyte cell therapy, either
      with bioartificial liver devices or hepatocyte transplantation, may help address
      this by delaying or preventing liver transplantation. Early clinical studies have
      shown promising results, however in most cases, the benefit has been short lived
      and so further research into these therapies is required. Alternative sources of
      hepatocytes, including stem cell-derived hepatocytes, are being investigated as
      the isolation of primary human hepatocytes is limited by the same shortage of
      donor organs. This review summarises the current clinical experience of
      hepatocyte cell therapy together with an overview of possible alternative sources
      of hepatocytes. Current and future areas for research that might lead towards the
      realisation of the full potential of hepatocyte cell therapy are discussed. 

PMID- 26212799
TI  - Genomewide association study on chronic periodontitis in Korean population:
      results from the Yangpyeong health cohort.
AB  - AIM: This study aims to locate the genes related to periodontitis through genome
      wide association study (GWAS) in Korean population. METHODS: Total of 677 adults
      aged 44-88 years were recruited from the Yangpyeong cohort in Korea. The
      participants did not have self-reported metabolic diseases, cardiovascular
      diseases or cancer. Periodontitis was assessed using alveolar bone loss from a
      digital panoramic radiograph and classified into three groups: normal to mild,
      moderate and severe periodontitis. DNA from blood samples were genotyped using
      the Illumina Human 1M-duo Beadchip. Multivariable logistic regression analysis in
      PLINK was applied to examine the single-nucleotide polymorphisms (SNPs) related
      to periodontitis after controlling for various confounders. RESULTS: Associations
      of three SNPs suggested TENM2 (rs4242220) and LDLRAD4 (rs12969041, rs2027756) as
      putative risk genes of chronic periodontitis (p-values <1 * 10-5 ). The odds
      ratio [95% confidence interval (CI)] of TENM2 was 0.53 (0.40-0.70) for moderate
      periodontitis and that of LDLRAD4 was 2.86 (1.92-4.27) for severe periodontitis.
      Two nonsynonymous SNPs of protein coding region and seven SNPs selected from
      previous reports showed nominal association. CONCLUSION: Our GWAS supports a
      previously reported gene of TENM2 and newly suggests LDLRAD4. These two genes'
      role on lipid metabolism may play a part in the molecular aetiology of
      periodontitis.

PMID- 26212800
TI  - Prediction of reversible IgG1 aggregation occurring in a size exclusion
      chromatography column is enabled through a model based approach.
AB  - One important aspect of antibody separation being studied today is aggregation,
      as this not only leads to a loss in yield, but aggregates can also be hazardous
      if injected into the body. The aim of this study was to determine whether the
      methodology applied in the previous study could be used to predict the
      aggregation of a different batch of IgG1, and to model the aggregation occurring
      in a SEC column. Aggregation was found to be reversible. The equilibrium
      parameter was found to be 272 M(-1) and the reaction kinetic parameter 1.33 * 10(
      5) s(-1) , both within the 95% confidence interval of the results obtained in the
      previous work. The effective diffusivities were estimated to be 1.45 * 10(-13)
      and 1.90 10(-14) m(2) /s for the monomers and dimers, respectively. Good
      agreement was found between the new model and the chromatograms obtained in the
      SEC experiments. The model was also able to predict the decrease of dimers due to
      the dilution and separation in the SEC column during long retention times. 

PMID- 26212801
TI  - Aplasia Cutis Congenita Associated with Fetus Papyraceus.
AB  - Aplasia cutis congenita (ACC), or congenital absence of skin, is a heterogeneous
      condition that may be due to varied mechanisms. ACC has rarely been reported in
      association with fetus papyraceus, representing a peculiar phenotype of ACC. We
      present six new cases of neonates born with symmetric ACC associated with
      intrauterine fetal demise of co-twins during the late first or early second
      trimester. 

PMID- 26212802
TI  - Performance of the same column in supercritical fluid chromatography and in
      liquid chromatography.
AB  - We have studied the chromatographic behavior of the homologous series of
      alkylbenzenes (ranging from octylbenzene to octadecylbenzene) on the same C18
      reversed-phase column in supercritical fluid chromatography (SFC) and reversed
      phase liquid chromatography (RPLC) at various experimental conditions, such as
      different eluent compositions, flow-rates, and mobile phase densities. The first
      and the second moments of the peaks were used to estimate the overall mass
      transfer processes in both chromatographic modes using the stochastic model of
      chromatography. The results confirm that in SFC - as the density of the mobile
      phase is influenced by the flow-rate - there is a broader variation of mass
      transfer properties than in liquid chromatography. As expected, the optimum
      mobile phase velocity is higher in SFC, but there is no real difference in the
      minimum value of plate height, i.e. in the optimum efficiency. 

PMID- 26212803
TI  - Carbon nanotubes and graphene modified screen-printed carbon electrodes as
      sensitive sensors for the determination of phytochelatins in plants using liquid
      chromatography with amperometric detection.
AB  - Nanomaterials are of great interest for the development of electrochemical
      sensors. Multi-walled carbon nanotubes and graphene were used to modify the
      working electrode surface of different screen-printed carbon electrodes (SPCE)
      with the aim of improving the sensitivity of the SPCE and comparing it with the
      conventional glassy carbon electrode. To assay the usability of these sensors, a
      HPLC methodology with amperometric detection was developed to analyze several
      phytochelatins in plants of Hordeum vulgare and Glycine max treated with Hg(II)
      or Cd(II) giving detection limits in the low MUmolL(-1) range. Phytochelatins are
      low molecular weight peptides with the general structure gamma-(Glu-Cys)n-Gly
      (n=2-5) which are synthesized in plants in the presence of heavy metal ions.
      These compounds can chelate heavy metal ions by the formation of complexes which,
      are transported to the vacuoles, where the toxicity is not threatening. For this
      reason phytochelatins are essential in the detoxification of heavy metal ions in
      plants. The developed HPLC method uses a mobile phase of 1% of formic acid in
      water with KNO3 or NaCl (pH=2.00) and 1% of formic acid in acetonitrile.
      Electrochemical detection at different carbon-based electrodes was used. Among
      the sensors tested, the conventional glassy carbon electrode offers the best
      sensitivity although modification improves the sensitivity of the SPCE.
      Glutathione and several isoforms of phytochelatin two were found in plant
      extracts of both studied species. 

PMID- 26212804
TI  - Aerosol-based detectors for liquid chromatography.
AB  - Aerosol-based detectors developed within the last few decades have increasingly
      addressed the need for sensitive, universal liquid chromatography detection in a
      wide variety of applications. Herein, we review the operating principles,
      instrumentation, analytical characteristics, and recent applications of the three
      general types of such detectors: evaporative light scattering detection (ELSD),
      condensation nucleation light scattering detection (CNLSD); commercially known as
      the nano-quantity analyte detector (NQAD), and charged aerosol detection (CAD).
      Included is a comparative evaluation of the operational and analytical
      characteristics of these detectors. 

PMID- 26212805
TI  - Instrumentation for analytical scale supercritical fluid chromatography.
AB  - Analytical scale supercritical fluid chromatography (SFC) is largely a sub
      discipline of high performance liquid chromatography (HPLC), in that most of the
      hardware and software can be used for either technique. The aspects that separate
      the 2 techniques stem from the use of carbon dioxide (CO2) as the main component
      of the mobile phase in SFC. The high compressibility and low viscosity of CO2
      mean that pumps, and autosamplers designed for HPLC either need to be modified or
      an alternate means of dealing with compressibility needs to be found. The
      inclusion of a back pressure regulator and a high pressure flow cell for any UV
      Vis detector are also necessary. Details of the various approaches, problems and
      solutions are described. Characteristics, such as adiabatic vs. isothermal
      compressibility, thermal gradients, and refractive index issues are dealt with in
      detail.

PMID- 26212806
TI  - Factors of Suppression of Immune Response in Patients with Pulmonary Tuberculosis
      and Eosinophilia.
AB  - We studied possible mechanisms of immunosuppression mediated by regulatory T
      cells that promotes suppression of antigen-specific immune response to
      Mycobacterium tuberculosis in patients with pulmonary tuberculosis and
      eosinophilia. It was shown that the number of CD4(+)CD25(+)Foxp3(+) regulatory T
      cells with immunosuppressive activity (Treg) increased in the peripheral blood of
      patients with disseminated destructive forms of pulmonary tuberculosis with
      multiple resistance of the causative agent to antituberculosis substances and
      eosinophilia. These changes were accompanied by imbalance in secretion of Treg
      associated cytokines (in vitro) manifested in hyperproduction of TGFbeta and IL
      10 and decreased production of IL-2. 

PMID- 26212807
TI  - Depressive Behavior and Monoamine Contents in Brain Structures of Rats During
      Chronic Overcrowding.
AB  - Effects of chronic overcrowding on the development of depressive-like behavior
      and changes in monoamine contents in the brain structures involved in the
      development of depression were studied in rats. It was shown that overcrowding
      increased grooming duration and did not change the number of crossed squares and
      postures in the open-field test. In the forced swimming test, overcrowding
      increased immobility time and deceased the duration of the first episode of
      active swimming, which attested to depressive-like behavior. Overcrowding reduced
      the content of dopamine in the striatum, its metabolites (homovanilic and
      dioxyphenylacetic acids) and dopamine metabolism rate in the hypothalamus, and
      increased the concentrations of norepinephrine, homovanilic acid, and
      dioxyphenylacetic acid in the olfactory bulb and homovanilic acid in the
      prefrontal cortex. No changes were found in the nucleus accumbens. Serotonin
      content did not change in all analyzed structures. It was hypothesized that the
      observed changes in the content of monoamines and their metabolites in certain
      brain structures could underlie the depressive-like behavior induced by
      overcrowding in rats. 

PMID- 26212808
TI  - Efficiency of Very Low Doses of Antibodies to S100 Protein in the Complex Therapy
      of Functional Dyspepsia in Children.
AB  - We showed the data on clinical efficiency of low doses of antibodies to brain
      specific protein S100 in the complex therapy of schoolchildren with painful
      variant of functional dyspepsia syndrome. Significant positive effects of the
      substance on the dynamics of epigastric pain, in particular, its duration, were
      found. The maximum clinical effect was observed in children with emotional
      disorders (~1/3 of all examined children). Along with significant decrease in
      frequency appearance and duration of pain syndrome, the substance also normalized
      emotional state and improved attention concentration in children.

PMID- 26212809
TI  - Lymphocyte Subpopulations and Cytokine Levels in Experimental
      Hyperhomocysteinemia.
AB  - Moderate exogenous hyperhomocysteinemia is associated with an increase in
      lymphocyte count (mainly at the expense of cytotoxic T cells), a 2-fold drop of
      the immunoregulatory index, and increase in TNF-alpha, IFN-gamma, and IL-17alpha
      concentrations in the serum and in mononuclear cells. Homocysteine concentration
      in the mononuclears remains unchanged. 

PMID- 26212810
TI  - Possible Recovery of Manifestation of Prolactin Receptor and Some of Its Target
      Proteins in the Liver and Kidney Cells of Female Rats after Relief of Cholestasis
      Complicated and Not Complicated by Hyperprolactinemia.
AB  - Immunohistochemistry with semi-quantitative analysis of computer images showed
      that prolactin receptor and cystic fi brosis transmembrane regulator (CFTR) in
      cholangiocytes of female rats elevated in cholestasis quickly respond to its
      relief. The effect of hyperprolactinemia on the extent of return of these
      proteins to baseline was different. Decompression of the bile duct abolishes the
      negative effect of hyperprolactinemia on CFTR expression and its positive effect
      on mrp3 expression in the proximal renal tubules. In renal medulla, mrp2
      expression decreased when cholestasis was induced against the background of
      hyperprolactinemia and increases after its removal. Prolactin receptors and CFTR
      in cholangiocytes are most susceptible to the decrease in bile duct pressure.
      Changes in the expression of the studied proteins after cholestasis relief are
      apparently associated with attenuated toxicity of the products removed by the
      kidneys, which abolishes the effects of prolactin. 

PMID- 26212811
TI  - Neuroprotective and Antioxidant Effects of Neuroglutam in Cerebral Ischemia.
AB  - We studied in vitro and in vivo neuroprotective and antioxidant properties of
      neuroglutam, a new glutamic acid derivative. In experiments on immortalized mouse
      hippocampal cell line HT22, neuroglutam exhibited a neuroprotective effect in the
      model of oxidative stress after its introduction, both before and after H2O2. In
      vivo study on animals treated with neuroglutam against the background of cerebral
      ischemia modeled by irreversible occlusion of the common carotid arteries showed
      that plasma level of TBA-active products was significantly lower and activities
      of cell antioxidant enzymes (superoxide dismutase and catalase) were higher than
      in control animals receiving saline under the same conditions.

PMID- 26212812
TI  - Comparative Study of Diuretic Activity of Hydroalcoholic Extracts from Medicinal
      Plants Containing Flavonoids.
AB  - Cherula and sticklewort tinctures exhibit rapid and short-lasting diuretic
      effect. Tinctures of tansy and immortelle are featured by rapid onset of the
      effect and prolonged action, while the tincture of common bearberry has a long
      latency period and prolonged action. Under normal conditions of gravity,
      flavonoid rutin stimulates diuresis only through tubular component; under
      hypergravity, simultaneously via glomerular and tubular components. 

PMID- 26212813
TI  - Effect of Pyrrolobenzimidazole Derivative RU-792 on Experimental Brain Ischemia.
AB  - Compound RU-792 showed pronounced anti-ischemic activity and improved survival of
      rats with brain ischemia by normalizing parameters of spontaneous motor activity
      and reducing neurological deficit within 3 post-operative days being superior to
      the reference drug mexidol by this parameter. RU-792 inhibited the formation of
      conjugated dienes and malonic dialdehyde and increased activity of the
      antioxidant enzyme glutathione peroxidase thereby modulating the parameters of
      free radical oxidation in rats subjected to ischemia more effectively than
      mexidol. 

PMID- 26212814
TI  - Anti-Parkinsonian Activity of Hemantane on a Model of Hemiparkinsonian Syndrome
      in Rats.
AB  - Hemantane demonstrated a pronounced antiparkinsonian activity in the model of
      hemiparkinsonian syndrome provoked in rats by unilateral intracerebral injection
      of 6-hydroxydopamine, which was comparable to efficacy of levodopa in decreasing
      the duration of cataleptogenic state and the degree of akinesia of the
      contralesional forelimb assessed in the cylinder test. In the stepping test,
      hemantane exerted a long-term effect in contrast to levodopa, which diminished
      its beneficial action to the treatment day 21. In the swing test, the behavior
      normalized only by hemantane. 

PMID- 26212815
TI  - Modifying Effects of Nanosized Diamonds on Hydrolytic Potential of Macrophages In
      Vitro.
AB  - The effects of nanosized particles (4-6 nm) of synthetic diamonds on mouse
      macrophage expression and secretion of lysosomal cathepsins (B and D) and MMP-1
      and MMP-9 were studied in vitro. Culturing of peritoneal macrophages in medium
      with diamond nanoparticles led to an increase in the counts of macrophages
      expressing the above enzymes and to stimulation of their secretion. However, the
      manifestations of these effects varied significantly for various enzymes. The
      data indicate modulation of macrophage functions by nanodiamonds. These results
      help better understand the possible role of the "corpuscular" xenobiotic factors
      in the pathogenesis of diseases associated with macrophage capturing of these
      factors irrespective of their chemical "activity". 

PMID- 26212816
TI  - Disorders in the Morphology and Nanostructure of Erythrocyte Membranes after Long
      term Storage of Erythrocyte Suspension: Atomic Force Microscopy Study.
AB  - Disorders in the erythrocyte morphology and structure of their membranes during
      long-term storage of erythrocyte suspension (30 days at 4 degrees C) were studied
      by atomic force microscopy. The morphology and nanostructure of erythrocyte
      membranes, biochemical parameters, ion exchange parameters, and hemoglobin
      spectra were recorded. The transformation of erythrocyte morphology and
      destruction of their membranes were observed throughout the storage period.
      Irreversible forms of spheroechinocytes and their fragments formed by the end of
      storage. The concentrations of potassium ions and lactate in solution of the
      blood preservatiive increased, while pH value decreased. Hemolysis detected by
      the erythrocyte "leakage" effect was observed starting from days 16-23 of
      storage. 

PMID- 26212817
TI  - Biology and Treatment of Paget's Disease of Bone.
AB  - Paget's disease of bone (PDB) is a common skeletal disorder characterized by
      increased and disorganized bone remodeling affecting one or more skeletal sites.
      Although some patients are asymptomatic others develop complications such as bone
      pain, deformity, nerve compression syndromes, and fragility fractures. Genetic
      factors play an important role in the pathogenesis of PDB and there is strong
      evidence that susceptibility is determined by variants within or close to genes
      that regulate osteoclast function. Environmental factors also play a key role but
      the nature of the environmental triggers is less clear. Bisphosphonates are a
      highly effective treatment for the elevations in bone turnover that are
      characteristic of PDB but it is unclear at present if they alter the natural
      history of the disease. Here, we review the epidemiology, clinical, cellular, and
      molecular abnormalities in PDB as well as environmental and genetic triggers, and
      current available treatment options.

PMID- 26212818
TI  - Corticotropin releasing factor up-regulates the expression and function of
      norepinephrine transporter in SK-N-BE (2) M17 cells.
AB  - Corticotropin releasing factor (CRF) has been implicated to act as a
      neurotransmitter or modulator in central nervous activation during stress. In
      this study, we examined the regulatory effect of CRF on the expression and
      function of the norepinephrine transporter (NET) in vitro. SK-N-BE (2) M17 cells
      were exposed to different concentrations of CRF for different periods. Results
      showed that exposure of cells to CRF significantly increased mRNA and protein
      levels of NET in a concentration- and time-dependent manner. The CRF-induced
      increase in NET expression was mimicked by agonists of either CRF receptor 1 or
      2. Furthermore, similar CRF treatments induced a parallel increase in the uptake
      of [(3) H] norepinephrine. Both increased expression and function of NET caused
      by CRF were abolished by simultaneous administration of CRF receptor antagonists,
      indicating a mediation by CRF receptors. However, there was no additive effect
      for the combination of both receptor antagonists. Chromatin immunoprecipitation
      assays confirm an increased acetylation of histone H3 on the NET promoter
      following treatment with CRF. Taken together, this study demonstrates that CRF up
      regulates the expression and function of NET in vitro. This regulation is
      mediated through CRF receptors and an epigenetic mechanism related to histone
      acetylation may be involved. This CRF-induced regulation on NET expression and
      function may play a role in development of stress-related depression and anxiety.
      This study demonstrated that corticotropin release factor (CRF) up-regulated the
      expression and function of norepinephrine transporter (NET) in a concentration-
      and time-dependent manner, through activation of CRF receptors and possible
      histone acetylation in NET promoter. The results indicate that their interaction
      may play an important role in stress-related physiological and pathological
      status. 

PMID- 26212820
TI  - Dealing with Dementia.

PMID- 26212819
TI  - High-sensitivity cardiac troponin T is more helpful in detecting peri-operative
      myocardial injury and apoptosis during coronary artery bypass graft surgery.
AB  - AIM: To determine whether there is a correlation between cardiac markers and peri
      operative myocardial injury (PMI) and apoptosis in coronary artery bypass graft
      (CABG) surgery and to compare the efficacy of cardiac markers to detect PMI.
      METHODS: The study population consisted of 37 patients (24 male, 13 female, mean
      age 63.4 +/- 8.9 years) undergoing elective CABG. Arterial and coronary sinus
      blood samples were collected just before aortic cross-clamping (pre-ACC) and
      after aortic declamping (post-ACC). Creatine kinase-MB isoenzyme (CK-MB)
      activity, and high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase-MB
      isoenzyme mass (CK-MB mass) and cardiac troponin I (cTnI) concentrations were
      measured in blood samples. Myocardial injury and apoptosis were examined in
      atrial biopsies. RESULTS: CABG caused PMI and apoptosis in all cases.
      Concentrations and net releases of cardiac markers significantly increased after
      aortic declamping (p < 0.001 for CK-MB and CK-MB mass, p < 0.01 for cTnI, p <
      0.05 for hs-cTnT). A positive correlation was found between apoptotic index (r =
      0.611, p < 0.001 for cTnI; r = 0.806, p < 0.001 for hs-cTnT), myocardial injury
      score (r = 0.544, p < 0.001 for cTnI; r = 0.719, p < 0.001 for hs-cTnT) and cTnI
      and hs-cTnT values in the post-ACC period. A positive correlation was found
      between apoptotic index (r = 0.507, p < 0.001), myocardial injury score (r =
      0.416, p = 0.010) and net release of hs-cTnT. Furthermore, a positive correlation
      was found between aortic cross-clamp (ACC) time (r = 0.448, p = 0.007),
      cardiopulmonary bypass (CPB) time (r = 0.342, p = 0.047) and net release of hs
      cTnT. CONCLUSION: Although both cTnI and hs-cTnT may be specific and efficacious
      markers of myocardial apoptosis and injury occurring during CABG with CPB, hs
      cTnT may be a more useful marker than cTnI to detect peri-operative myocardial
      apoptosis and injury.

PMID- 26212821
TI  - Dementia, screening, targets, and incentives: Primum non nocere.

PMID- 26212822
TI  - Clinical decision making in dementia: mapping the minefields.

PMID- 26212823
TI  - Gastro-oesophageal reflux disease: illness or illusion?

PMID- 26212824
TI  - Financial incentives and professionalism: another fine mess.

PMID- 26212826
TI  - Paying for the NHS.

PMID- 26212827
TI  - Author's response.

PMID- 26212828
TI  - Assisted dying: we all need to be happier to help.

PMID- 26212829
TI  - Psychiatric assessment of patients with dementia in the community.

PMID- 26212830
TI  - Anorexia and the power of the GP.

PMID- 26212831
TI  - Too much medicine in the Middle East?

PMID- 26212832
TI  - Giving intermittent catheter users more choice.

PMID- 26212833
TI  - Bring Hippocrates to the people and save the NHS.

PMID- 26212834
TI  - Practice nurses, Ehlers-Danlos syndrome, fitness to drive, and Balint groups.

PMID- 26212835
TI  - The Ordinary Chaos of Psychosis.

PMID- 26212836
TI  - Gods and Heroes.

PMID- 26212837
TI  - State of the Union - The Home Nations at the 56th Venice Biennale.

PMID- 26212839
TI  - Learning my music how I learn my medicine.

PMID- 26212840
TI  - Best interest clinical decision making for care home residents with advanced
      dementia.

PMID- 26212841
TI  - Harnessing primary care to enhance recovery from severe mental illness.

PMID- 26212842
TI  - 8th Julian Tudor Hart Lecture 2014: Include me out, exclude you in.

PMID- 26212843
TI  - The oak processionary moth: a new health hazard?

PMID- 26212844
TI  - Clinical history for diagnosis of dementia in men: Caerphilly Prospective Study.
AB  - BACKGROUND: Diagnosis of dementia often requires specialist referral and
      detailed, time-consuming assessments. AIM: To investigate the utility of simple
      clinical items that non-specialist clinicians could use, in addition to routine
      practice, to diagnose all-cause dementia syndrome. DESIGN AND SETTING: Cross
      sectional diagnostic test accuracy study. Participants were identified from the
      electoral roll and general practice lists in Caerphilly and adjoining villages in
      South Wales, UK. METHOD: Participants (1225 men aged 45-59 years) were screened
      for cognitive impairment using the Cambridge Cognitive Examination, CAMCOG, at
      phase 5 of the Caerphilly Prospective Study (CaPS). Index tests were a
      standardised clinical evaluation, neurological examination, and individual items
      on the Informant Questionnaire for Cognitive Disorders in the Elderly (IQCODE).
      RESULTS: Two-hundred and five men who screened positive (68%) and 45 (4.8%) who
      screened negative were seen, with 59 diagnosed with dementia. The model
      comprising problems with personal finance and planning had an area under the
      curve (AUC) of 0.92 (95% confidence interval [CI] = 0.86 to 0.97), positive
      likelihood ratio (LR+) of 23.7 (95% CI = 5.88 to 95.6), negative likelihood ratio
      (LR-) of 0.41 (95% CI = 0.27 to 0.62). The best single item for ruling out was no
      problems learning to use new gadgets (LR- of 0.22, 95% CI = 0.11 to 0.43).
      CONCLUSION: This study found that three simple questions have high utility for
      diagnosing dementia in men who are cognitively screened. If confirmed, this could
      lead to less burdensome assessment where clinical assessment suggests possible
      dementia.

PMID- 26212845
TI  - Quality care provision for older people: an interview study with patients and
      primary healthcare professionals.
AB  - BACKGROUND: In recent years, primary health care for the ageing population has
      become increasingly complex. AIM: This study sought to explore the views and
      needs of healthcare professionals and older patients relating to primary care in
      order to identify focal areas for improving primary health care for older people.
      DESIGN AND SETTING: This research was structured as a mixed interview study with
      focus groups and individual interviews. Participants were made up of primary
      healthcare professionals and older patients. Patients were recruited from five
      elderly care homes in a small city in the southern part of the Netherlands.
      METHOD: All interviews were transcribed verbatim and analysed by two individual
      researchers applying constant comparative analysis. Data collection proceeded
      until saturation was reached. RESULTS: Participants in the study agreed about the
      need for primary care for older patients, and showed sympathy with one another's
      perspectives. They did note, however, a number of obstacles hindering good
      healthcare provision. The major themes that arose were: 'autonomy and
      independence', 'organisational barriers', and 'professional expertise'.
      Participants generally noted that it is important to clarify differences in
      perspectives about good care between patients and healthcare professionals.
      CONCLUSION: Effective primary care intervention for older patients requires
      mutual understanding of the expectations and goals of all parties involved. There
      are a number of important requirements, especially accessible patient information
      in the form of care plans; specialist training for nurses and GPs on complex care
      and multimorbidity; and training on discussing autonomy, goal setting, and shared
      care. Further improvement in health care for older people and its evaluation
      research should focus on these requirements.

PMID- 26212846
TI  - Simplified sleep restriction for insomnia in general practice: a randomised
      controlled trial.
AB  - BACKGROUND: Insomnia is common in primary care. Cognitive behavioural therapy for
      insomnia (CBT-I) is effective but requires more time than is available in the
      general practice consultation. Sleep restriction is one behavioural component of
      CBT-I. AIM: To assess whether simplified sleep restriction (SSR) can be effective
      in improving sleep in primary insomnia. DESIGN AND SETTING: Randomised controlled
      trial of patients in urban general practice settings in Auckland, New Zealand.
      METHOD: Adults with persistent primary insomnia and no mental health or
      significant comorbidity were eligible. Intervention patients received SSR
      instructions and sleep hygiene advice. Control patients received sleep hygiene
      advice alone. Primary outcomes included change in sleep quality at 6 months
      measured by the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index
      (ISI), and sleep efficiency (SE%). The proportion of participants reaching a
      predefined 'insomnia remission' treatment response was calculated. RESULTS:
      Ninety-seven patients were randomised and 94 (97%) completed the study. At 6
      month follow-up, SSR participants had improved PSQI scores (6.2 versus 8.4,
      P<0.001), ISI scores (8.6 versus 11.1, P = 0.001), actigraphy-assessed SE%
      (difference 2.2%, P = 0.006), and reduced fatigue (difference -2.3 units, P =
      0.04), compared with controls. SSR produced higher rates of treatment response
      (67% [28 out of 42] versus 41% [20 out of 49]); number needed to treat = 4 (95%
      CI = 2.0 to 19.0). Controlling for age, sex, and severity of insomnia, the
      adjusted odds ratio for insomnia remission was 2.7 (95% CI = 1.1 to 6.5). There
      were no significant differences in other outcomes or adverse effects. CONCLUSION:
      SSR is an effective brief intervention in adults with primary insomnia and no
      comorbidities, suitable for use in general practice.

PMID- 26212847
TI  - Clinical features of metastatic cancer in primary care: a case-control study
      using medical records.
AB  - BACKGROUND: How metastatic cancer initially presents is largely unknown. AIM: To
      identify clinical features of metastatic cancer in primary care. DESIGN AND
      SETTING: Case-control study in 11 general practices in Devon, UK. METHOD: Cases
      of patients who had died with metastatic breast, colorectal, or prostate cancer
      were selected. In addition, two control groups were formed of patients with the
      same primary cancer but without metastases ('cancer controls') and patients
      without cancer ('healthy controls'), matched for age, sex, and practice. All
      symptoms, signs, and laboratory test abnormalities in the year before metastasis
      were identified. The primary analysis used conditional logistic regression.
      RESULTS: In total, 162 cases, 152 cancer controls, and 145 healthy controls were
      studied. Common symptoms associated with cancer were: vomiting, 40 (25%) cases
      and 13 (9%) cancer controls (multivariable odds ratio [OR] 3.5, 95% confidence
      interval [CI] = 1.3 to 9.4, P = 0.011); low back pain, 38 (24%) cases and 17
      (11%) cancer controls (OR 2.5, 95% CI = 1.1 to 5.6, P = 0.032); loss of appetite,
      32 (20%) cases and nine (6%) cancer controls (OR 4.0, 95% CI = 1.2 to 13.2, P =
      0.021); and shoulder pain, 27 (17%) cases and eight (5%) cancer controls (OR 5.3,
      95% CI = 1.6 to 18, P = 0.007). Groin pain was uncommon, but strongly associated
      (16 [10%] cases and one [1%] cancer control [OR 10, 95% CI = 1.2 to 82, P =
      0.032]), as was pleural disease (nine [6%] cases and one [1%] cancer control [OR
      10, 95% CI = 1.1 to 92, P = 0.038]). CONCLUSION: These features of disseminated
      cancer have been reported before in studies from secondary care, but the scarcity
      of specific symptoms (such as local pain) and the fairly common occurrence of non
      specific symptoms (vomiting and loss of appetite) is important and may explain
      delays in the diagnosis of metastases.

PMID- 26212848
TI  - A clinical prediction rule for meniscal tears in primary care: development and
      internal validation using a multicentre study.
AB  - BACKGROUND: In primary care, meniscal tears are difficult to detect. A quick and
      easy clinical prediction rule based on patient history and a single meniscal test
      may help physicians to identify high-risk patients for referral for magnetic
      resonance imaging (MRI). AIM: The study objective was to develop and internally
      validate a clinical prediction rule (CPR) for the detection of meniscal tears in
      primary care. DESIGN AND SETTING: In a cross-sectional multicentre study, 121
      participants from primary care were included if they were aged 18-65 years with
      knee complaints that existed for <6 months, and who were suspected to suffer from
      a meniscal tear. METHOD: One diagnostic physical meniscal test and 14 clinical
      variables were considered to be predictors of MRI outcome. Using known predictors
      for the presence of meniscal tears, a 'quick and easy' CPR was derived. RESULTS:
      The final CPR included the variables sex, age, weight-bearing during trauma,
      performing sports, effusion, warmth, discolouration, and Deep Squat test. The
      final model had an AUC of 0.76 (95% CI = 0.72 to 0.80). A cut-point of 150 points
      yielded an overall sensitivity of 86.1% and a specificity of 45.5%. For this cut
      point, the positive predictive value was 55.0%, and the negative predictive value
      was 81.1%. A scoring system was provided including the corresponding predicted
      probabilities for a meniscal tear. CONCLUSION: The CPR improved the detection of
      meniscal tears in primary care. Further evaluation of the CPR in new primary care
      patients is needed, however, to assess its usefulness.

PMID- 26212849
TI  - Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a
      randomised controlled trial in primary care.
AB  - BACKGROUND: The effectiveness of diclofenac versus paracetamol in primary care
      patients with pain caused by knee osteoarthritis is unclear. AIM: To assess the
      effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and
      12 weeks in patients with knee osteoarthritis. DESIGN AND SETTING: Randomised
      controlled trial in general practice. METHOD: There were 104 patients included in
      the study, they were aged >=45 years consulting their GP with knee pain caused by
      knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or
      paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain
      severity, and knee pain and function measured with the Knee Injury and
      Osteoarthritis Outcome Score (KOOS). RESULTS: Over a period of 2- and 4-weeks
      follow-up, no significant difference in daily knee pain was found between the
      patient groups: estimated differences of 0.5 (95% CI = -0.2 to 1.3) and -0.2 (95%
      CI = -1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant
      differences were found between both groups for KOOS pain: estimated difference of
      -2.8 (95% CI = -10.7 to 5.1) and KOOS function of -2.7 (-10.6 to 5.0).
      CONCLUSION: Over a period of 2- and 4-weeks follow-up no significant difference
      in daily measured knee pain severity was found between primary care patients with
      knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12
      weeks follow-up no significant differences were found regarding KOOS pain and
      KOOS function between both groups. Patients more frequently reported minor
      adverse events after taking diclofenac (64%) than paracetamol (46%).

PMID- 26212850
TI  - Statin prescribing for primary prevention of cardiovascular disease: a cross
      sectional, observational study.
AB  - BACKGROUND: The updated (2014) National Institute for Health and Care Excellence
      (NICE) guideline lowered the recommended threshold for statin prescription from
      20% to 10% 10-year cardiovascular disease (CVD) risk. AIM: To determine the
      characteristics of patients prescribed statins for primary prevention according
      to their CVD risk. DESIGN AND SETTING: Cross-sectional study in primary care
      settings in the three east London CCGs (Newham, City and Hackney, and Tower
      Hamlets). METHOD: Data were extracted from electronic health records of 930 000
      patients registered with 137 of 141 general practices for a year ending 1 April
      2014. RESULTS: Of 341 099 patients aged 30-74 years, excluding those with CVD or
      diabetes, 22 393 were prescribed statins and had a 10-year CVD risk recorded. Of
      these, 9828 (43.9%) had a CVD risk >=20%, 7121 (31.8%) had a CVD risk of 10-19%,
      and 5444 (24.3%) had a CVD risk <10%. Statins were prescribed to 9828/19 755
      (49.7%) of those at >=20% CVD risk, to 7121/37 111 (19.2%) of those with CVD risk
      10-19%, and to 5444/146 676 (3.7%) of those with CVD risk <10%. Statin
      prescription below the 20% CVD risk threshold targeted individuals in the 10-19%
      risk band in association with hypertension, high serum cholesterol, positive
      family history, older age, and south Asian ethnicity. CONCLUSION: This study
      confirms continuing undertreatment of patients at highest CVD risk (>=20%). GPs
      prescribed statins to only one-fifth of those in the 10-19% risk band usually in
      association with known major risk factors. Only 3.7% of individuals below 10%
      were prescribed statins.

PMID- 26212851
TI  - Depth of the patient-doctor relationship and content of general practice
      consultations: cross-sectional study.
AB  - BACKGROUND: Patient-doctor continuity is valued by both parties, yet the effect
      of the depth of the patient-doctor relationship on the content of consultations
      in general practice is unknown. AIM: To assess whether differences in the depth
      of relationship between a patient and their GP affects the length of
      consultations, and the number and type of problems and issues raised during a
      consultation. DESIGN AND SETTING: Cross-sectional study in 22 GP practices in the
      UK. METHOD: GP consultations (n = 229) were videotaped and the number of problems
      and aspects of those problems and issues identified. Patients completed the
      Patient-Doctor Depth of Relationship (PDDR) and General Practice Assessment
      Questionnaire-communication (GPAQc) scales. Associations were explored using
      multivariable linear and logistic regression. RESULTS: Complete data were
      available on 190 participants consulting 30 GPs. In unadjusted analysis, patients
      with a deep relationship with their GP discussed more problems (mean 2.8) and
      issues (mean 4.7) compared with those with a moderate (2.4 problems; 4.0 issues)
      or shallow (2.3 problems; 3.8 issues) relationship. Patients with deep
      relationships had consultations that were on average 118 seconds (95% CI = 1 to
      236) longer than those with shallow relationships. Adjustment for participant and
      GP factors attenuated these relationships, although the main trends persisted.
      CONCLUSION: A greater number of problems and issues may be raised in a
      consultation when patients have a deeper relationship with their GP. Over several
      clinical encounters each year, this may be associated with significant benefits
      to patients and efficiencies in GP consultations and warrants further
      investigation.

PMID- 26212852
TI  - Patients' views on pay for performance in France: a qualitative study in primary
      care.
AB  - BACKGROUND: Pay for performance was implemented in 2009 in France. The system was
      optional at first and then became widespread. Since 2012, it has been standard
      for most GPs. Several studies have attempted to investigate its efficiency and
      the GP's opinion of the system, but few studies have yet to examine the patient's
      view. AIM: To gain an understanding of the views of French family practice
      patients about pay for performance. DESIGN AND SETTING: Forty patients were
      interviewed between March and July 2013 in the Ile-de-France region, of France.
      METHOD: A qualitative study using semi-structured individual interviews, in
      primary care. RESULTS: Most of the patients did not know what pay for performance
      was and stated that they had not noticed any change in care since the system
      began. Some patients noted the possible benefits in the quality of care, such as
      an improvement in follow-up and prevention, better information provided by the
      GP, and a decrease in the volume of prescriptions and therefore health costs.
      Other patients were concerned about potential downsides, such as an
      overprescription of unnecessary medical treatments, an increase in health costs,
      patient selection, and standardised consultations that do not necessarily take
      into account the patient's individual concerns. CONCLUSION: Since implementation
      of pay for performance, patients had not noticed any modification in their
      medical care. They could understand the need for change in the remuneration
      policy and expressed their agreement about performance-based remuneration if, and
      only if, it is not the cause of depersonalised health care.

PMID- 26212853
TI  - Diagnosis of chronic exertional compartment syndrome in primary care.

PMID- 26212854
TI  - Electrolytes Ageing in Lithium-ion Batteries: A Mechanistic Study from Picosecond
      to Long Timescales.
AB  - The ageing phenomena occurring in various diethyl carbonate/LiPF6 solutions are
      studied using gamma and pulse radiolysis as a tool to generate similar species as
      the ones occurring in electrolysis of Li-ion batteries (LIBs). According to
      picosecond pulse radiolysis experiments, the reaction of the electron with
      (Li(+), PF6(-)) is ultrafast, leading to the formation of fluoride anions that
      can then precipitate into LiF(s). Moreover, direct radiation-matter interaction
      with the salt produces reactive fluorine atoms forming HF(g) and C2H5F(g). The
      strong Lewis acid PF5 is also formed. This species then forms various
      R(1)R(2)R(3) P=O molecules, where R is mainly -F, -OH, and -OC2H5. Substitution
      reactions take place and oligomers are slowly formed. Similar results were
      obtained in the ageing of an electrochemical cell filled with the same model
      solution. This study demonstrates that radiolysis enables a description of the
      reactivity in LIBs from the picosecond timescale until a few days.

PMID- 26212855
TI  - Detecting a Defective Casing Seal at the Top of a Bedrock Aquifer.
AB  - An improperly sealed casing can produce a direct hydraulic connection between two
      or more originally isolated aquifers with important consequences regarding
      groundwater quantity and quality. A recent study by Richard et al. (2014)
      investigated a monitoring well installed in a fractured rock aquifer with a
      defective casing seal at the soil-bedrock interface. A hydraulic short circuit
      was detected that produced some leakage between the rock and the overlying
      deposits. A falling-head permeability test performed in this well showed that the
      usual method of data interpretation is not valid in this particular case due to
      the presence of a piezometric error. This error is the direct result of the
      preferential flow originating from the hydraulic short circuit and the subsequent
      re-equilibration of the piezometric levels of both aquifers in the vicinity of
      the inlet and the outlet of the defective seal. Numerical simulations of
      groundwater circulation around the well support the observed impact of the
      hydraulic short circuit on the results of the falling-head permeability test.
      These observations demonstrate that a properly designed falling-head permeability
      test may be useful in the detection of defective casing seals. 

PMID- 26212856
TI  - Immunogenetics of systemic sclerosis: Defining heritability, functional variants
      and shared-autoimmunity pathways.
AB  - Systemic sclerosis (SSc) is a clinically heterogeneous connective tissue disorder
      of complex etiology. The development of large-scale genetic studies, such as
      genome-wide association studies (GWASs) or the Immunochip platform, has achieved
      remarkable progress in the knowledge of the genetic background of SSc. Herein, we
      provide an updated picture SSc genetic factors, offering an insight into their
      role in pathogenic mechanisms that characterize the disease. We review the most
      recent findings in the HLA region and the well-established non-HLA loci. Up to 18
      non-HLA risk factors fulfilled the selected criteria and they were classified
      according to their role in the innate or adaptive immune response, in apoptosis,
      autophagy or fibrosis. Additionally, SSc heritability has remained as a
      controversial question since twin studies provided low SSc heritability
      estimates. However, we have recalculated the lower bond of narrow sense SSc
      heritability using GWAS data. Remarkably, our results suggest a greater influence
      of genetics on SSc than previously reported. Furthermore, we also offer a
      functional classification of SSc-associated SNPs and their proxies, based on
      annotated data, to provide clues for the identification of causal variants in
      these loci. Finally, we explore the genetic overlap between SSc and other
      autoimmune diseases (ADs). The vast majority of SSc risk loci are shared with at
      least one additional AD, being the overlap between SSc and systemic lupus
      erythematous the largest. Nevertheless, we found that an important portion of SSc
      risk factors are also common to rheumatoid arthritis or primary biliary
      cirrhosis. Considering all these evidences, we are confident that future research
      will be successful in understanding the relevant altered pathways in SSc and in
      identifying new biomarkers and therapeutic targets for the disease.

PMID- 26212857
TI  - Ultrafast spontaneous emission source using plasmonic nanoantennas.
AB  - Typical emitters such as molecules, quantum dots and semiconductor quantum wells
      have slow spontaneous emission with lifetimes of 1-10 ns, creating a mismatch
      with high-speed nanoscale optoelectronic devices such as light-emitting diodes,
      single-photon sources and lasers. Here we experimentally demonstrate an ultrafast
      (<11 ps) yet efficient source of spontaneous emission, corresponding to an
      emission rate exceeding 90 GHz, using a hybrid structure of single plasmonic
      nanopatch antennas coupled to colloidal quantum dots. The antennas consist of
      silver nanocubes coupled to a gold film separated by a thin polymer spacer layer
      and colloidal core-shell quantum dots, a stable and technologically relevant
      emitter. We show an increase in the spontaneous emission rate of a factor of 880
      and simultaneously a 2,300-fold enhancement in the total fluorescence intensity,
      which indicates a high radiative quantum efficiency of ~50%. The nanopatch
      antenna geometry can be tuned from the visible to the near infrared, providing a
      promising approach for nanophotonics based on ultrafast spontaneous emission. 

PMID- 26212858
TI  - Intra-Isthmus Reentry Flutter Localizing at Pouch of Cavotricuspid Isthmus.

PMID- 26212859
TI  - Induction of ovine trophoblast cell fusion by fematrin-1 in vitro.
AB  - Endogenous retroviruses present in the genomes take a specific role in placental
      formation in various vertebrates, including bovine and sheep. Fematrin-1, which
      is the envelope (Env) protein of bovine endogenous retrovirus found in bovine
      placenta, is involved in the formation of fetomaternal hybrid cells in cattle
      placenta. This study was conducted to clarify whether fematrin-1 possesses
      fusogenic activity in trophoblast cells. Another question is whether Env proteins
      only have species-specific activity or not. For this, fematrin-1 gene was
      transfected in ovine trophoblast cells, and we examined fusogenic activity with
      Cos-7 cells. Although fematrin-1 fusogenic activity was detected in both neutral
      and acidic pH conditions, acidic condition significantly enhanced it. These
      activities were rather weaker than those of vesicular stomatitis virus G protein
      as a positive control. However, the ratio of fematrin-1 and vesicular stomatitis
      virus G protein fusion index was confirmed similar to those in the previous
      reports. Some fusion cells showed multinucleate cells. These results imply that
      fematrin-1 is involved in the formation of trophoblast hybrid cells even in
      different species trophoblastic cells. 

PMID- 26212860
TI  - Perfluoropropenyl-containing phosphines from HFC replacements.
AB  - A series of new perfluoropropenyl-containing phosphines of the type R3-nP(E
      CF[double bond, length as m-dash]CFCF3)n (R = Ph, iPr, n = 1, 2; R = tBu, n = 2)
      have been prepared from the reaction of the hydrofluoroolefin Z-CF3CF[double
      bond, length as m-dash]CFH (HFO-1225ye) with base and the appropriate
      chlorophosphine, while reaction with Cl2PCH2CH2PCl2 gave (CF3CF[double bond,
      length as m-dash]CF)2PCH2CH2P(CF[double bond, length as m-dash]CFCF3)2, the first
      example of a bidentate perfluoroalkenyl-containing phosphine. An alternative
      route to these phosphines based on the room- or low-temperature deprotonation of
      CF3CF2CH2F (HFC-236ea) gives mainly the E-isomer, but also a small amount of the
      Z-isomer, the ratio of which depends on the reaction temperature. All of the
      phosphines could be readily oxidised with either H2O2 or urea.H2O2, and the
      phosphine selenides R3-nP(Se)(E-CF[double bond, length as m-dash]CFCF3)n (R = Ph,
      n = 1,2; R = iPr, n = 1; R = tBu, n = 2) were also prepared. The steric and
      electronic properties of these ligands were determined based on their
      platinum(ii), palladium(ii) and molybdenum carbonyl complexes. The crystal
      structures of (CF3CF[double bond, length as m-dash]CF)2PCH2CH2P(CF[double bond,
      length as m-dash]CFCF3)2, (CF3CF[double bond, length as m
      dash]CF)2P(O)CH2CH2P(O)(CF[double bond, length as m-dash]CFCF3)2,
      iPr2P(Se)(CF[double bond, length as m-dash]CFCF3)2, trans-[PtCl2{Ph(3-n)P(E
      CF[double bond, length as m-dash]CFCF3)n}2] (n = 1 or 2), trans-[PdCl2{R2P(E
      CF[double bond, length as m-dash]CFCF3)}2] (R = Ph, iPr) and
      [Mo(CO)4{(CF3CF[double bond, length as m-dash]CF)2PCH2CH2P(CF[double bond, length
      as m-dash]CFCF3)2}] are reported. 

PMID- 26212861
TI  - Protective HSP70 Induction by Z-Ligustilide against Oxygen-Glucose Deprivation
      Injury via Activation of the MAPK Pathway but Not of HSF1.
AB  - Heat-shock protein 70 (HSP70) is known to function as a protective molecular
      chaperone that is massively induced in response to misfolded proteins following
      cerebral ischemia. The objective of this study was to characterize HSP70
      induction by Z-ligustilide and explore its potential role in protection against
      cerebral ischemia-reperfusion injury. Our results demonstrated that the
      intranasal administration of Z-ligustilide reduced infarct volume and improved
      neurological function in a rat stroke model. Meanwhile, Z-ligustilide enhanced
      the cell viability of PC12 cells insulted by oxygen-glucose deprivation
      reoxygenation (OGD-Reoxy) and decreased apoptotic and necrotic cell death.
      Importantly, Z-ligustilide induced HSP70 expression both in vitro and in vivo.
      Although heat-shock factor 1 (HSF1) nuclear translocation was promoted by Z
      ligustilide, HSP70-based heat-shock element (HSE)-binding luciferase activity was
      not activated, and HSP70 expression responsive to Z-ligustilide was not
      attenuated by HSE decoy oligonucleotides. However, Z-ligustilide significantly
      activated the phosphorylation of mitogen-activated protein kinases (MAPKs).
      Further inhibition of MAPK activity by specific inhibitors attenuated HSP70
      induction by Z-ligustilide. Meanwhile, downregulation of HSP70 using KNK437, an
      HSP70 synthesis inhibitor, or small hairpin RNA (shRNA) significantly attenuated
      the protection of Z-ligustilide against OGD-Reoxy-induced injury. Moreover, the
      application of specific inhibitors of MAPKs also achieved similar results.
      Finally, Z-ligustilide alleviated the accumulation of ubiquitinated proteins
      induced by OGD-Reoxy, which was inhibited by HSP70-shRNA. Taken together, our
      results demonstrated that Z-ligustilide may induce protective HSP70 expression
      via the activation of the MAPK pathway, but not canonical HSF1 transcription.
      HSP70 plays a key role in the protection of Z-ligustilide against OGD-Reoxy
      induced injury. 

PMID- 26212862
TI  - The dynamics of FLOWERING LOCUS T expression encodes long-day information.
AB  - Long days repeatedly enhance the expression of the FLOWERING LOCUS T (FT) gene
      during the evening and early night. This signal induces flowering despite low FT
      expression the rest of the day. To investigate whether this temporal behaviour
      transmits information, plants of Arabidopsis thaliana were exposed to different
      day-night cycles, including combinations that induced FT expression out of normal
      hours. Flowering time best correlated with the integral of FT expression over
      several days, corrected for a higher evening and early night sensitivity to FT.
      We generated a system to induce FT expression in a leaf removed 8-12 h later. The
      expression of flowering genes in the apex and flowering required cycles of
      induction repeated over several days. Evening and early night FT induction was
      the most effective. The temporal pattern of FT expression encodes information
      that discriminates long days from other inputs. 

PMID- 26212863
TI  - Knowledge, perceptions, attitudes and willingness to report to work in an
      earthquake: A pilot study comparing Canadian versus Israeli hospital nursing
      staff.
AB  - BACKGROUND: Health practitioners are expected to respond effectively to an
      earthquake event and provide lifesaving treatment to an influx of casualties.
      Understanding the factors that may influence nurses' willingness to report (WTR)
      in different social contexts and preparedness approaches is crucial for improving
      preparedness of medical facilities. METHODS: A questionnaire based on a
      previously validated methodology was used to assess demographic characteristics,
      knowledge, perceptions, attitudes and WTR of nurses after an earthquake. The
      questionnaire was disseminated among a sample of 56 Israeli and 127 Canadian
      nurses, from two tertiary care hospitals, located in risk regions. RESULTS: WTR
      was generally higher among Canadian versus Israeli nurses (74% vs. 64%).
      Knowledge and perceptions of organizational-efficacy were generally higher among
      Israeli nurses. 'Concern for family's well-being' and 'professional commitment to
      care' were reported by the largest proportion of nurses as factors that might
      influence WTR. A common significant predictor of WTR among both samples was the
      belief that 'colleagues will also report to work'. CONCLUSION: Although different
      preparedness approaches or emergency experience in Canada and Israel may cause
      differences in nurses' preparedness, some factors seem to be cross-cultural and
      may play a key role in increasing nurses' willingness to report after an
      earthquake.

PMID- 26212864
TI  - Ratiometric fluorescence detection of silver ions using thioflavin T-based
      organic/inorganic hybrid supraparticles.
AB  - In this work, we present a new type of functional organic/inorganic hybrid
      supraparticle that spontaneously assembles from silver ions (Ag(+)), iodide ions
      (I(-)) and thioflavin T (ThT) under aqueous solution conditions. ThT alone in
      aqueous solution was weakly fluorescent with an emission band at 494 nm, which
      was related to the monomer. However, in the above-mentioned hybrid supraparticle
      (i.e., ThT@AgI SP) structure, the ThT monomer can form a dimer with a new
      emission band. The new band shifted to 546 nm and the emission intensity
      increased. We further present a facile strategy of reversible fluorescence
      switching of ThT by a simple cation (Ag(+)) and anions (I(-) and S(2-)), which
      can be employed for the ratiometric fluorescence detection of Ag(+) with high
      sensitivity and selectivity. The linear range of detecting Ag(+) was from 100 nM
      to 10 MUM, with a limit of detection as low as approximately 50 nM. Moreover, it
      can be successfully applied for the operation of a logic gate system and to the
      sensing of Ag(+) in real water samples. 

PMID- 26212865
TI  - A new nitinol stent for use in superior vena cava syndrome. Initial clinical
      experience.
AB  - AIM: The aim of the study was to assess the early clinical experience with the
      Zilver Vena stent in treating patients with malignant superior vena cava
      syndrome. METHODS: Demographic, procedural, and follow-up data of 12 patients
      (seven women; mean age 69 years) treated for superior vena cava syndrome with in
      all 21 Zilver Vena stents between March 2012 and October 2013 were
      retrospectively reviewed. All cavographies and contrast enhanced CT related to
      the treatment and during follow-up were evaluated and the patients had clinical
      follow-up until dead. They were all in terminal state at the time of stent
      deployment. RESULTS: All patients had superior vena cava obstruction and clinical
      superior vena cava syndrome caused by malignant expansive mediastinal disease
      (eight patients non-small cell lung cancer and four small cell lung cancer). The
      technical success with deployment of the stents in the intended position was 75%.
      Good clinical effect with resolution of superior vena cava syndrome was achieved
      in 11 of the 12 patients (92%). CONCLUSION: The Zilver Vena stent appeared to be
      safe, easy to deploy, and showed good clinical outcome. The high radial force of
      the stent might be of advantage in these patients with expanding masses around
      the superior vena cava.

PMID- 26212866
TI  - Clinical usefulness of pneumococcal urinary antigen test, stratified by disease
      severity and serotypes.
AB  - Early diagnosis of pneumococcal pneumonia facilitates appropriate antibiotic
      therapy. The urinary antigen test (UAT) is known to be useful for the diagnosis
      of pneumococcal pneumonia. This study aimed to evaluate the usefulness of UAT in
      the 13-valent pneumococcal conjugated vaccine (PCV13) era. Community-acquired
      pneumonia (CAP) cases aged >=19 years were reviewed retrospectively. This study
      evaluated the utility of Streptococcus pneumoniae UAT (BinaxNOW((r)) assay) for
      diagnosis of pneumococcal CAP, and the relation of the UAT positive rate to age,
      comorbidities, pneumonia severity, and pneumococcal serotypes. Among 752
      microbiologically identified CAP cases, S. pneumoniae (36.7%) was the most common
      isolate, and of those cases, 56.4% were positive for UAT. UAT positivity varied
      by pneumococcal serotype (serotype 3, 50%; 9V/9A, 85%; 11A/11E, 54%; 14, 36.4%;
      19A, 50%; and 23F, 37.5%), and was significantly increased since 2012, two years
      after introduction of PCV13. The positive rate of UAT was significantly related
      to CRP level (P = 0.007) and lobar pneumonia (P = 0.006), but not to age, co
      morbidities or prior antibiotic therapy. In conclusion, urinary antigen detection
      varied depending on the S. pneumoniae serotype. In the PCV13 era, the serotype
      distribution of pneumococcal pneumonia may be changing, and the clinical
      usefulness of UAT needs to be monitored. The positive rate of UAT may be
      influenced by a localized bacterial burden and host reactions.

PMID- 26212867
TI  - Peeking from the blindfold.

PMID- 26212868
TI  - Hepatitis C virus reinfection after sustained virological response in HIV
      infected patients with chronic hepatitis C.
AB  - OBJECTIVES: To assess the incidence of hepatitis C virus (HCV) reinfections after
      therapy-induced clearance in HIV-coinfected patients with prior chronic hepatitis
      C. METHODS: Eighty-four HIV-infected subjects, who had previously achieved
      sustained virological response (SVR) after being treated of chronic hepatitis C,
      were analyzed. In all of them, at least yearly HCV RNA determinations were
      carried out during a median (range) of 34 (12-146) months. RESULTS: Seventy-two
      (86%) subjects had been people who inject drugs (PWID), of whom 11 (15%)
      continued to use snorted or injected drugs during the follow-up. Four (4.76%)
      patients showed HCV reinfection (incidence 1.21 [95% confidence interval: 0.3
      3.09] cases per 100 person-years). These patients maintained risk factors for HCV
      infection. In three cases, HCV genotype switched. Phylogenetic analysis of the
      remaining case suggested reinfection from his sexual partner. CONCLUSION: The
      incidence of HCV reinfection in the overall population of HIV-coinfected patients
      who achieved SVR after being treated against chronic hepatitis C is low. A low
      frequency of risk behavior is the main factor accounting for this modest rate of
      reinfection. The possibility of reinfection should not be considered a reason
      against treatment of HCV infection with direct acting antivirals in PWID.

PMID- 26212869
TI  - Ibrutinib promising in subtype of DLBCL.

PMID- 26212870
TI  - Cancer strategy to help NHS achieve world-class outcomes.

PMID- 26212871
TI  - T-cell receptor therapy shows promise in multiple myeloma.

PMID- 26212872
TI  - Treatment adherence, efficacy, and safety of etanercept in patients with active
      psoriatic arthritis and peripheral involvement in Belgium for 66 months (PROVE
      study).
AB  - OBJECTIVES: To describe the long-term adherence, efficacy, and safety in patients
      with psoriatic arthritis (PsA) treated with etanercept (ETN) in a daily clinical
      setting in Belgium. METHODS: The PROVE study was a prospective, multi-centre,
      open-label, observational study in patients with active PsA who had previously
      failed disease-modifying anti-rheumatic drugs. Patients were treated with ETN
      prescribed by their physician and adherence was monitored over 66 months.
      RESULTS: A total of 303 patients were enrolled (polyarticular-type n=264;
      oligoarticular-type n=39). 156 (51.5%) patients adhered to the treatment until
      the end of the study. The mean study duration was 4.0 (SD, 1.9) years. The most
      common reasons for discontinuing were non-response (35.9%), patient lost to
      follow-up (20.7%), and reasons unrelated to ETN (20.0%). Males adhered to
      treatment significantly longer than females (5.0 vs. 3.9 years; p<0.0001). After
      6 months, 49.0% of patients with active synovitis at the start of the study had
      zero joints with synovitis, and this proportion increased to 77.6% by month 66
      (p<0.001 for all time points vs. baseline). In polyarticular-type patients, the
      mean total Health Assessment Questionnaire (HAQ) score (0-60) decreased from 27.0
      (95% CI 25.9-28.1) to 9.7 (8.5-10.9; 64.8% improvement; p<0.001) after 6 months
      and to 7.7 (6.2-9.3; 66.6% improvement; p<0.001) after 66 months. Treatment
      related adverse events were reported in 177 (58.8%) of patients, and 53 (17.6%)
      patients reported serious adverse events related to treatment. CONCLUSIONS: In
      these patients with active PsA from daily clinical practice, adherence to ETN was
      high observed over 5.5 years and it was well tolerated.

PMID- 26212873
TI  - Simultaneous cecal volvulus and gastric erosion secondary to laparoscopic
      adjustable gastric band.

PMID- 26212874
TI  - Extramedullary haematopoiesis in chronic lymphocytic leukaemia.

PMID- 26212875
TI  - Effects of temperature on the quality of black garlic.
AB  - BACKGROUND: Black garlic is a type of garlic product that is generally produced
      by heating raw garlic at high temperature with controlled humidity for more than
      30 days. Black garlic has appeared on the market for many years. It is crucial to
      investigate the characteristics of quality formation of black garlic during
      processing at various temperatures. RESULTS: In this study, fresh garlic was
      processed to black garlic at temperatures of 60, 70, 80 and 90  degrees C.
      Moisture, amino acid nitrogen and allicin contents decreased gradually during
      thermal processing of various temperatures. Reducing sugar, 5
      hydroxymethylfurfural, total phenols, total acids contents and browning
      increased. The changing rate of quality indicators and flavour of black garlic
      varied at different temperatures. Browning intensity reached about 74 when black
      garlic aged. The sensory score was significantly higher in black garlic aged at
      70  degrees C (39.95 +/- 0.31) compared with that at other temperatures,
      suggesting that 70  degrees C might facilitate formation of good quality and
      flavour of black garlic during processing. CONCLUSION: Temperature had a
      remarkable impact on the quality and flavour of black garlic. (c) 2015 Society of
      Chemical Industry.

PMID- 26212876
TI  - The influence of left ventricular geometry on left atrial phasic function in
      hypertensive patients.
AB  - OBJECTIVE: We aimed to investigate left atrial (LA) phasic function in
      hypertensive patients with different geometric patterns using two-dimensional
      (2DE) and three-dimensional (3DE) echocardiography. METHODS: This cross-sectional
      study included 213 hypertensive subjects who underwent a complete 2DE and 3DE
      examination. The new updated criteria for left ventricular (LV) geometry, which
      consider LV mass index, LV end-diastolic diameter and relative wall thickness,
      were applied. According to this classification, the subjects were divided into
      six groups: normal geometry, concentric remodeling, eccentric non-dilated left
      ventricular hypertrophy (LVH), concentric LVH, dilated LVH and concentric-dilated
      LVH. RESULTS: 2DE and 3DE LA volumes gradually increased from normal LV geometry
      to concentric and concentric-dilated LVH. LA reservoir and conduit functions,
      estimated by 2DE and 3DE LA total and passive emptying fractions, were decreased
      in subjects with concentric and concentric-dilated LVH. LA booster pump function
      was increased in patients with concentric, dilated and concentric-dilated LVH
      compared to subjects with normal LV geometry. The same results regarding LA
      phasic function were provided by 2DE strain analysis. Concentric, dilated and non
      concentric dilated LVH were associated with LA enlargement independently of main
      demographic and clinical features. CONCLUSION: LV geometric patterns
      significantly influence LA phasic function. Concentric and dilated LVH patterns
      have the most prominent negative effect on LA enlargement assessed by both 2DE
      and 3DE.

PMID- 26212878
TI  - Neural representations of emotion are organized around abstract event features.
AB  - Research on emotion attribution has tended to focus on the perception of overt
      expressions of at most five or six basic emotions. However, our ability to
      identify others' emotional states is not limited to perception of these canonical
      expressions. Instead, we make fine-grained inferences about what others feel
      based on the situations they encounter, relying on knowledge of the eliciting
      conditions for different emotions. In the present research, we provide convergent
      behavioral and neural evidence concerning the representations underlying these
      concepts. First, we find that patterns of activity in mentalizing regions contain
      information about subtle emotional distinctions conveyed through verbal
      descriptions of eliciting situations. Second, we identify a space of abstract
      situation features that well captures the emotion discriminations subjects make
      behaviorally and show that this feature space outperforms competing models in
      capturing the similarity space of neural patterns in these regions. Together, the
      data suggest that our knowledge of others' emotions is abstract and high
      dimensional, that brain regions selective for mental state reasoning support
      relatively subtle distinctions between emotion concepts, and that the neural
      representations in these regions are not reducible to more primitive affective
      dimensions such as valence and arousal. 

PMID- 26212879
TI  - Early-Life Stress Triggers Juvenile Zebra Finches to Switch Social Learning
      Strategies.
AB  - Stress during early life can cause disease and cognitive impairment in humans and
      non-humans alike. However, stress and other environmental factors can also
      program developmental pathways. We investigate whether differential exposure to
      developmental stress can drive divergent social learning strategies between
      siblings. In many species, juveniles acquire essential foraging skills by copying
      others: they can copy peers (horizontal social learning), learn from their
      parents (vertical social learning), or learn from other adults (oblique social
      learning). However, whether juveniles' learning strategies are condition
      dependent largely remains a mystery. We found that juvenile zebra finches living
      in flocks socially learned novel foraging skills exclusively from adults. By
      experimentally manipulating developmental stress, we further show that social
      learning targets are phenotypically plastic. While control juveniles learned
      foraging skills from their parents, their siblings, exposed as nestlings to
      experimentally elevated stress hormone levels, learned exclusively from unrelated
      adults. Thus, early-life conditions triggered individuals to switch strategies
      from vertical to oblique social learning. This switch could arise from stress
      induced differences in developmental rate, cognitive and physical state, or the
      use of stress as an environmental cue. Acquisition of alternative social learning
      strategies may impact juveniles' fit to their environment and ultimately change
      their developmental trajectories.

PMID- 26212880
TI  - Distinct Neural Circuits Control Rhythm Inhibition and Spitting by the Myogenic
      Pharynx of C. elegans.
AB  - Neural circuits have long been known to modulate myogenic muscles such as the
      heart, yet a mechanistic understanding at the cellular and molecular levels
      remains limited. We studied how light inhibits pumping of the Caenorhabditis
      elegans pharynx, a myogenic muscular pump for feeding, and found three neural
      circuits that alter pumping. First, light inhibits pumping via the I2 neuron
      monosynaptic circuit. Our electron microscopic reconstruction of the anterior
      pharynx revealed evidence for synapses from I2 onto muscle that were missing from
      the published connectome, and we show that these "missed synapses" are likely
      functional. Second, light inhibits pumping through the RIP-I1-MC neuron
      polysynaptic circuit, in which an inhibitory signal is likely transmitted from
      outside the pharynx into the pharynx in a manner analogous to how the mammalian
      autonomic nervous system controls the heart. Third, light causes a novel
      pharyngeal behavior, reversal of flow or "spitting," which is induced by the M1
      neuron. These three neural circuits show that neurons can control a myogenic
      muscle organ not only by changing the contraction rate but also by altering the
      functional consequences of the contraction itself, transforming swallowing into
      spitting. Our observations also illustrate why connectome builders and users
      should be cognizant that functional synaptic connections might exist despite the
      absence of a declared synapse in the connectome.

PMID- 26212881
TI  - Morphogenesis of the Fission Yeast Cell through Cell Wall Expansion.
AB  - The shape of walled cells such as fungi, bacteria, and plants are determined by
      the cell wall. Models for cell morphogenesis postulate that the effects of turgor
      pressure and mechanical properties of the cell wall can explain the shapes of
      these diverse cell types. However, in general, these models await validation
      through quantitative experiments. Fission yeast Schizosaccharomyces pombe are rod
      shaped cells that grow by tip extension and then divide medially through
      formation of a cell wall septum. Upon cell separation after cytokinesis, the new
      cell ends adopt a rounded morphology. Here, we show that this shape is generated
      by a very simple mechanical-based mechanism in which turgor pressure inflates the
      elastic cell wall in the absence of cell growth. This process is independent of
      actin and new cell wall synthesis. To model this morphological change, we first
      estimate the mechanical properties of the cell wall using several approaches. The
      lateral cell wall behaves as an isotropic elastic material with a Young's modulus
      of 50 +/- 10 MPa inflated by a turgor pressure estimated to be 1.5 +/- 0.2 MPa.
      Based upon these parameters, we develop a quantitative mechanical-based model for
      new end formation that reveals that the cell wall at the new end expands into its
      characteristic rounded shape in part because it is softer than the mature lateral
      wall. These studies provide a simple example of how turgor pressure expands the
      elastic cell wall to generate a particular cell shape.

PMID- 26212882
TI  - An insect with selective control of egg coloration.
AB  - The color and patterning of animal eggs has important consequences for offspring
      survival. There are examples of between-species and polymorphic differences in
      egg coloration in birds and amphibians [1-3], as well as cases of birds and
      insects whose nutritional status or age can cause within-individual variation in
      egg pigmentation [4-6]. However, no studies to date have demonstrated that
      individual animals can selectively control the color of their eggs. Here, we show
      that individual females of the predatory stink bug Podisus maculiventris can
      control the pigmentation of their eggs during oviposition, as a response to
      environmental conditions. The color of egg masses produced by individual females
      can range from pale yellow to dark black/brown. Females tend to lay darker eggs,
      which are more resistant to UV radiation, on the upper surface of leaves where UV
      exposure is highest in nature. Conversely, they lay lighter eggs on the
      undersides of leaves. However, egg color is not determined by the intensity of UV
      radiation falling on the surface where they are laid. Rather, female stink bugs
      appear to use a visual assessment of oviposition substrate reflectance to
      determine egg color. Unexpectedly, biochemical analyses revealed that the egg
      pigment is not melanin, the most ubiquitous light-absorbing pigment in animals.
      Our study offers the first example of an animal able to selectively control the
      color of its eggs. 

PMID- 26212883
TI  - Representation of numerical and sequential patterns in macaque and human brains.
AB  - The ability to extract deep structures from auditory sequences is a fundamental
      prerequisite of language acquisition. Using fMRI in untrained macaques and
      humans, we investigated the brain areas involved in representing two abstract
      properties of a series of tones: total number of items and tone-repetition
      pattern. Both species represented the number of tones in intraparietal and dorsal
      premotor areas and the tone-repetition pattern in ventral prefrontal cortex and
      basal ganglia. However, we observed a joint sensitivity to both parameters only
      in humans, within bilateral inferior frontal and superior temporal regions. In
      the left hemisphere, those sites coincided with areas involved in language
      processing. Thus, while some abstract properties of auditory sequences are
      available to non-human primates, a recently evolved circuit may endow humans with
      a unique ability for representing linguistic and non-linguistic sequences in a
      unified manner. 

PMID- 26212884
TI  - Spiralian phylogeny informs the evolution of microscopic lineages.
AB  - Despite rapid advances in the study of metazoan evolutionary history [1],
      phylogenomic analyses have so far neglected a number of microscopic lineages that
      possess a unique combination of characters and are thus informative for our
      understanding of morphological evolution. Chief among these lineages are the
      recently described animal groups Micrognathozoa and Loricifera, as well as the
      two interstitial "Problematica" Diurodrilus and Lobatocerebrum [2]. These genera
      show a certain resemblance to Annelida in their cuticle and gut [3, 4]; however,
      both lack primary annelid characters such as segmentation and chaetae [5].
      Moreover, they show unique features such as an inverted body-wall musculature or
      a novel pharyngeal organ. This and their ciliated epidermis have led some to
      propose relationships with other microscopic spiralians, namely Platyhelminthes,
      Gastrotricha, and in the case of Diurodrilus, with Micrognathozoa [6, 7]-lineages
      that are grouped by some analyses into "Platyzoa," a clade whose status remains
      uncertain [1, 8-11]. Here, we assess the interrelationships among the meiofaunal
      and macrofaunal members of Spiralia using 402 orthologs mined from genome and
      transcriptome assemblies of 90 taxa. Lobatocerebrum and Diurodrilus are found to
      be deeply nested members of Annelida, and unequivocal support is found for
      Micrognathozoa as the sister group of Rotifera. Analyses using site-heterogeneous
      substitution models further recover a lophophorate clade and position Loricifera
      + Priapulida as sister group to the remaining Ecdysozoa. Finally, with several
      meiofaunal lineages branching off early in the diversification of Spiralia, the
      emerging concept of a microscopic, acoelomate, direct-developing ancestor of
      Spiralia is reviewed. 

PMID- 26212885
TI  - The evolution of annelids reveals two adaptive routes to the interstitial realm.
AB  - Many animals permanently inhabit the marine interstitium, the space between sand
      grains [1, 2]. Different evolutionary scenarios may explain the existence of
      interstitial animals [3, 4]. These scenarios include (1) that the interstitial
      realm is the ancestral habitat of bilaterians [5, 6], (2) that interstitial taxa
      evolved from larger ancestors by miniaturization, or (3) progenesis [3]. The
      first view mirrors the former hypothesis that interstitial annelids, called
      archiannelids, were at the base of the annelid radiation [7]. Based on
      morphological data, however, progenesis is generally favored for interstitial
      annelids today [3, 4, 8]. Herein, our phylogenomic approach revealed that
      interstitial archiannelids are robustly placed into two groups nested within the
      annelid tree. Evolution of the first group comprising among others Dinophilidae
      is best explained by progenesis. In contrast, the second group comprising
      Protodrilida and Polygordiidae appears to have evolved by stepwise
      miniaturization adapting from coarser to finer sediments. Thus, in addition to
      progenesis [3, 4], miniaturization, thought to be too slow for an adaptation to
      the interstitium [3], is an important second route allowing adaptation to
      interstitial environments. Both progenesis and miniaturization should be
      considered when investigating evolution of interstitial taxa [1, 3]. 

PMID- 26212887
TI  - Mechanical response comparison in an implant overdenture retained by ball
      attachments on conventional regular and mini dental implants: a finite element
      analysis.
AB  - This study investigates the bone/implant mechanical responses in an implant
      overdenture retained by ball attachments on two conventional regular dental
      implants (RDI) and four mini dental implants (MDI) using finite element (FE)
      analysis. Two FE models of overdentures retained by RDIs and MDIs for a
      mandibular edentulous patient with validation within 6% variation errors were
      constructed by integrating CT images and CAD system. Bone grafting resulted in 2
      mm thickness at the buccal side constructed for the RDIs-supported model to mimic
      the bone augmentation condition for the atrophic alveolar ridge. Nonlinear
      hyperelastic material and frictional contact element were used to simulate
      characteristic of the ball attachment-retained overdentures. The results showed
      that a denture supported by MDIs presented higher surrounding bone strains than
      those supported by RDIs under different load conditions. Maximum bone micro
      strains were up to 6437/2987 and 13323/5856 for MDIs/RDIs under single centric
      and lateral contacts, respectively. Corresponding values were 4429/2579 and
      9557/5774 under multi- centric and lateral contacts, respectively. Bone micro
      strains increased 2.06 and 1.96-folds under single contact, 2.16 and 2.24-folds
      under multiple contacts for MDIs and RDIs when lateral to axial loads were
      compared. The maximum RDIs and MDIs implant stresses in all simulated cases were
      found by far lower than their yield strength. Overdentures retained using ball
      attachments on MDIs in poor edentulous bone structure increase the surrounding
      bone strain over the critical value, thereby damaging the bone when compared to
      the RDIs. Eliminating the occlusal single contact and oblique load of an implant
      retained overdenture reduces the risk for failure.

PMID- 26212886
TI  - Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical,
      structural and pathway analysis.
AB  - Thiamin (vitamin B1) is a pharmacological agent boosting central metabolism
      through the action of the coenzyme thiamin diphosphate (ThDP). However, positive
      effects, including improved cognition, of high thiamin doses in neurodegeneration
      may be observed without increased ThDP or ThDP-dependent enzymes in brain. Here,
      we determine protein partners and metabolic pathways where thiamin acts beyond
      its coenzyme role. Malate dehydrogenase, glutamate dehydrogenase and pyridoxal
      kinase were identified as abundant proteins binding to thiamin- or thiazolium
      modified sorbents. Kinetic studies, supported by structural analysis, revealed
      allosteric regulation of these proteins by thiamin and/or its derivatives.
      Thiamin triphosphate and adenylated thiamin triphosphate activate glutamate
      dehydrogenase. Thiamin and ThDP regulate malate dehydrogenase isoforms and
      pyridoxal kinase. Thiamin regulation of enzymes related to malate-aspartate
      shuttle may impact on malate/citrate exchange, responsible for exporting acetyl
      residues from mitochondria. Indeed, bioinformatic analyses found an association
      between thiamin- and thiazolium-binding proteins and the term acetylation. Our
      interdisciplinary study shows that thiamin is not only a coenzyme for acetyl-CoA
      production, but also an allosteric regulator of acetyl-CoA metabolism including
      regulatory acetylation of proteins and acetylcholine biosynthesis. Moreover,
      thiamin action in neurodegeneration may also involve neurodegeneration-related 14
      3-3, DJ-1 and beta-amyloid precursor proteins identified among the thiamin-
      and/or thiazolium-binding proteins. 

PMID- 26212888
TI  - Wilderness medicine race for preclinical students.
AB  - OBJECTIVES: Introducing medical students to wilderness medicine provides skills
      in leadership, teamwork, improvisation, and managing medical emergencies;
      however, wilderness medicine (WM) education is typically reserved for senior
      medical students and often requires expensive travel. Here, we describe the
      Winter Wilderness Medicine Race (WWMR). The race was held at a large allopathic
      medical school and targeted towards preclinical medical students. Race planning
      was performed by senior medical students with the supervision of doctors from the
      Department of Emergency Medicine. We hypothesized that this intervention in
      medical education would enhance students' WM knowledge, and build teamwork and
      improvisational skills. METHODS: The research involved a one day WM race that
      required teams of first- and second-year medical students to navigate a 5-km
      course and complete medical scenarios. Races that were held annually between 2011
      and 2014 are included in the study. The educational effectiveness of the race was
      evaluated by pre- and post-race knowledge assessments of the medical students
      participating in a WWMR. Qualitative data regarding student perceptions of the
      skills learned were obtained by focus group interviews. Wilderness medicine
      provides skills in leadership, teamwork, improvisation and managing medical
      emergencies RESULTS: Between 2011 and 2014, 122 preclinical medical students from
      a Midwestern US allopathic medical school participated in the study. Overall, the
      mean scores for pre- and post-race knowledge assessments were 48 and 85 per cent,
      respectively, a 37 per cent increase in scores (p < 0.0001). Participants cited
      improvisational and communication skills as the most important educational
      feature of the race. CONCLUSIONS: The Winter Wilderness Medicine Race (WWMR)
      enhanced preclinical medical students' wilderness medicine knowledge, teamwork
      skills and improvisational abilities.

PMID- 26212889
TI  - Analysis of the Financial Return of Electronic Health Records.

PMID- 26212890
TI  - A qualitative thematic review: emotional labour in healthcare settings.
AB  - AIMS: To identify the range of emotional labour employed by healthcare
      professionals in a healthcare setting and implications of this for staff and
      organisations. BACKGROUND: In a healthcare setting, emotional labour is the act
      or skill involved in the caring role, in recognizing the emotions of others and
      in managing our own. DESIGN: A thematic synthesis of qualitative studies which
      included emotion work theory in their design, employed qualitative methods and
      were situated in a healthcare setting. The reporting of the review was informed
      by the ENTREQ framework. DATA SOURCES: 6 databases were searched between 1979
      2014. REVIEW METHODS: Studies were included if they were qualitative, employed
      emotion work theory and were written in English. Papers were appraised and themes
      identified. Thirteen papers were included. RESULTS: The reviewed studies
      identified four key themes: (1) The professionalization of emotion and gendered
      aspects of emotional labour; (2) Intrapersonal aspects of emotional labour - how
      healthcare workers manage their own emotions in the workplace; (3) Collegial and
      organisational sources of emotional labour; (4) Support and training needs of
      professionals CONCLUSION: This review identified gendered, personal,
      organisational, collegial and socio-cultural sources of and barriers to emotional
      labour in healthcare settings. The review highlights the importance of ensuring
      emotional labour is recognized and valued, ensuring support and supervision is in
      place to enable staff to cope with the varied emotional demands of their work.

PMID- 26212891
TI  - Transperitoneal versus extraperitoneal robot-assisted laparoscopic radical
      prostatectomy: A prospective single surgeon randomized comparative study.
AB  - OBJECTIVES: To compare operative, pathological, and functional results of
      transperitoneal and extraperitoneal robot-assisted laparoscopic radical
      prostatectomy carried out by a single surgeon. METHODS: After having experience
      with 32 transperitoneal laparoscopic radical prostatectomies, 317 extraperitoneal
      laparoscopic radical prostatectomies, 30 transperitoneal robot-assisted
      laparoscopic radical prostatectomies and 10 extraperitoneal robot-assisted
      laparoscopic radical prostatectomies, 120 patients with prostate cancer were
      enrolled in this prospective randomized study and underwent either
      transperitoneal or extraperitoneal robot-assisted laparoscopic radical
      prostatectomy. The main outcome parameters between the two study groups were
      compared. RESULTS: No significant difference was found for age, body mass index,
      preoperative prostate-specific antigen, clinical and pathological stage, Gleason
      score on biopsy and prostatectomy specimen, tumor volume, positive surgical
      margin, and lymph node status. Transperitoneal robot-assisted laparoscopic
      radical prostatectomy had shorter trocar insertion time (16.0 vs 25.9 min for
      transperitoneal robot-assisted laparoscopic radical prostatectomy and
      extraperitoneal robot-assisted laparoscopic radical prostatectomy, P < 0.001),
      whereas extraperitoneal robot-assisted laparoscopic radical prostatectomy had
      shorter console time (101.5 vs 118.3 min, respectively, P < 0.001). Total
      operation time and total anesthesia time were found to be shorter in
      extraperitoneal robot-assisted laparoscopic radical prostatectomy, without
      statistical significance (200.9 vs 193.2 min; 221.8 vs 213.3 min, respectively).
      Estimated blood loss was found to be lower for extraperitoneal robot-assisted
      laparoscopic radical prostatectomy (P = 0.001). Catheterization and
      hospitalization times were observed to be shorter in extraperitoneal robot
      assisted laparoscopic radical prostatectomy (7.3 vs 5.8 days and 3.1 vs 2.3 days
      for transperitoneal robot-assisted laparoscopic radical prostatectomy and
      extraperitoneal robot-assisted laparoscopic radical prostatectomy, respectively,
      P < 0.05). The time to oral diet was significantly shorter in extraperitoneal
      robot-assisted laparoscopic radical prostatectomy (32.3 vs 20.1 h, P = 0.031).
      Functional outcomes (continence and erection) and complication rates were similar
      in both groups. CONCLUSIONS: Extraperitoneal robot-assisted laparoscopic radical
      prostatectomy seems to be a good alternative to transperitoneal robot-assisted
      laparoscopic radical prostatectomy with similar operative, pathological and
      functional results. As the surgical field remains away from the bowel,
      postoperative return to normal diet and early discharge can be favored.

PMID- 26212892
TI  - Global ecological impacts of invasive species in aquatic ecosystems.
AB  - The introduction of invasive species, which often differ functionally from the
      components of the recipient community, generates ecological impacts that
      propagate along the food web. This review aims to determine how consistent the
      impacts of aquatic invasions are across taxa and habitats. To that end, we
      present a global meta-analysis from 151 publications (733 cases), covering a wide
      range of invaders (primary producers, filter collectors, omnivores and
      predators), resident aquatic community components (macrophytes, phytoplankton,
      zooplankton, benthic invertebrates and fish) and habitats (rivers, lakes and
      estuaries). Our synthesis suggests a strong negative influence of invasive
      species on the abundance of aquatic communities, particularly macrophytes,
      zooplankton and fish. In contrast, there was no general evidence for a decrease
      in species diversity in invaded habitats, suggesting a time lag between rapid
      abundance changes and local extinctions. Invaded habitats showed increased water
      turbidity, nitrogen and organic matter concentration, which are related to the
      capacity of invaders to transform habitats and increase eutrophication. The
      expansion of invasive macrophytes caused the largest decrease in fish abundance,
      the filtering activity of filter collectors depleted planktonic communities,
      omnivores (including both facultative and obligate herbivores) were responsible
      for the greatest decline in macrophyte abundance, and benthic invertebrates were
      most negatively affected by the introduction of new predators. These impacts were
      relatively consistent across habitats and experimental approaches. Based on our
      results, we propose a framework of positive and negative links between invasive
      species at four trophic positions and the five different components of recipient
      communities. This framework incorporates both direct biotic interactions
      (predation, competition, grazing) and indirect changes to the water
      physicochemical conditions mediated by invaders (habitat alteration). Considering
      the strong trophic links that characterize aquatic ecosystems, this framework is
      relevant to anticipate the far-reaching consequences of biological invasions on
      the structure and functionality of aquatic ecosystems. 

PMID- 26212894
TI  - The infected heart: ventriculoseptal abscess and intracardiac fistulization.
AB  - Infective endocarditis is a rare but potentially deadly infection of the
      endocardial layer, which can involve the valves of the heart among other
      structures. The extraordinarily rare complication seen in this case involves
      extensive damage manifesting in an aortic root abscess resulting in an abnormal
      communication between the aorta and the atrium known as an aortocavitary fistula
      (Eur Heart J 2005;26:288-297; Pediatr Cardiol 2011;32:1057-1059; J Am Coll
      Cardiol 1991;18:663-667). As the disease progresses, wading through the complex
      symptoms, which may seem unrelated, represents a key challenge in diagnosis. This
      case describes both early and late findings of endocarditis and highlights a rare
      complication in which rapid diagnosis and early surgical intervention before the
      development of hemodynamic sequelae are paramount. In this case, infective
      endocarditis, a great masquerader in this case, provided a challenging diagnostic
      situation, a very rare complication, and commonalities of disease characteristics
      that health care provider should appreciate.

PMID- 26212895
TI  - Deep Brain Stimulation for Treatment-Resistant Psychiatric Illnesses: What Has
      Gone Wrong and What Should We Do Next?

PMID- 26212896
TI  - The Use of Ketamine for the Treatment of Depression in the Context of Psychotic
      Symptoms: To the Editor.

PMID- 26212897
TI  - The Relationship of Common Risk Variants and Polygenic Risk for Schizophrenia to
      Sensorimotor Gating.
AB  - BACKGROUND: Prepulse inhibition (PPI) of the startle reflex has been suggested as
      a candidate endophenotype for schizophrenia research, as it shows high
      heritability and has been found deficient in schizophrenia spectrum disorders.
      The objectives of the study were to 1) identify common genetic variants
      associated with baseline startle and PPI; 2) estimate the single nucleotide
      polymorphism heritability; and 3) examine the relationship of polygenic score for
      schizophrenia with baseline startle and PPI. METHODS: A cohort of healthy young
      male subjects (n = 1493) originating from the Learning on Genetics of
      Schizophrenia Spectrum project was assessed for baseline startle and PPI. The
      most recent genome-wide association study in schizophrenia from the Psychiatric
      Genomics Consortium 2 was used to calculate polygenic scores. RESULTS: Eleven
      loci showed suggestive association (p < 10(-6)) with baseline startle and PPI in
      the discovery cohort. Additional genotyping in a replication cohort identified
      genome-wide significant association at two loci (rs61810702 and rs4718984). These
      loci were co-localized with expression quantitative trait loci associated with
      gene expression of nerve growth factor (NGF) and calneuron 1 (CALN1) genes.
      Estimation of the genetic and environmental contributions to baseline startle and
      PPI showed a substantial single nucleotide polymorphism heritability for 120-ms
      PPI stimuli. Increased polygenic risk score for schizophrenia was associated with
      reduced PPI. CONCLUSIONS: Common genetic variation has an important role in the
      etiology of schizophrenia and PPI impairments. Overall, these data support the
      idea that PPI is a valid endophenotype that can be used to explore the genetic
      architecture of schizophrenia.

PMID- 26212898
TI  - The Anxiolytic Actions of 2-Arachidonoylglycerol: Converging Evidence From Two
      Recent Genetic Endocannabinoid Deficiency Models.

PMID- 26212899
TI  - Reply to: Intranasal Oxytocin Mechanisms Can Be Better Understood, but Its
      Effects on Social Cognition and Behavior Are Not to Be Sniffed At.

PMID- 26212900
TI  - Intranasal Oxytocin Mechanisms Can Be Better Understood, but Its Effects on
      Social Cognition and Behavior Are Not to Be Sniffed At.

PMID- 26212901
TI  - Efficient Scheme for Perfect Collective Einstein-Podolsky-Rosen Steering.
AB  - A practical scheme for the demonstration of perfect one-sided device-independent
      quantum secret sharing is proposed. The scheme involves a three-mode
      optomechanical system in which a pair of independent cavity modes is driven by
      short laser pulses and interact with a movable mirror. We demonstrate that by
      tuning the laser frequency to the blue (anti-Stokes) sideband of the average
      frequency of the cavity modes, the modes become mutually coherent and then may
      collectively steer the mirror mode to a perfect Einstein-Podolsky-Rosen state.
      The scheme is shown to be experimentally feasible, it is robust against the
      frequency difference between the modes, mechanical thermal noise and damping, and
      coupling strengths of the cavity modes to the mirror. 

PMID- 26212902
TI  - Causal attribution in individuals with subclinical and clinical autism spectrum
      disorder: An fMRI study.
AB  - This neuroimaging study compares brain activation during causal attribution to
      three different attribution loci (i.e., self, another person, and situation)
      across a typical population without (N = 20) or with subclinical autism spectrum
      symptoms (N = 18) and a clinical population with autism spectrum disorder (ASD; N
      = 11). While they underwent fMRI, all participants read short sentences
      describing positive and negative behaviors and thoughts of another person
      directed toward the participant (i.e., "you"). Participants were then asked to
      attribute these behaviors to themselves, the other person, or the situation.
      Behavioral measures revealed self-serving attributions (i.e., attributing
      positive events to the self, while attributing negative events externally from
      the self) in all three participant groups. Neural measures revealed a great deal
      of shared activation across the three attribution loci and across the three
      participant groups in the temporo-parietal junction, the posterior superior
      sulcus, and the precuneus. Comparison between groups revealed more widespread
      activation in both subclinical and clinical ASD participants, which may be
      indicative of the extraneural resources these participants invest to compensate
      their impairments.

PMID- 26212903
TI  - Brief Isolation Changes Nociceptive Behaviors and Compromises Drug Tests in Mice.
AB  - Herding with a litter is known to comfort rodents, whereas isolation and grouping
      with noncagemates provoke stress. The effects of stress induced by isolation and
      grouping with noncagemates on pain responses, and their underlying mechanisms
      remain elusive. We assessed the effect of isolation, a common condition during
      behavioral tests, and of grouping on defecation and pain behaviors of mice. Fecal
      pellets were counted 2 hours after exposure to the test chamber. It is
      significantly more in the isolated mice than in the grouped mice. Hindpaw
      withdrawal threshold and withdrawal latency were adopted as the indicatives of
      mechanical and thermal pain sensitivities, respectively. Interestingly, isolated
      mice showed higher pain thresholds than mice grouping with cagemates, and even
      those with noncagemates, indicating analgesic effects. Such effects were reduced
      by intrathecal injection of 0.01 mg/kg of naloxone (opioid receptor antagonist),
      atosiban (oxytocin and vasopressin receptor antagonist), and ketanserin (5-HT
      receptor antagonist). Intraperitoneal delivery of 1 mg/kg of naloxone and
      atosiban, but not ketanserin, also alleviated the isolation-induced analgesic
      effects. In contrast, these drugs at the same dose had no significant effect on
      the mice grouping with cagemates. In addition, the effect of morphine on thermal
      pain was more robust in the mice grouping with cagemates than in the isolated
      mice. These data demonstrated that brief isolation caused analgesia, mediated by
      endogenous opioidergic, oxytocinergic, and serotonergic pathways. These results
      indicate that isolation during pain behavioral tests can affect pain responses
      and the efficacy of drugs; thus, nociception tests should be conducted in
      grouping.

PMID- 26212904
TI  - Background Levels of Salivary-alpha-amylase Plus Foreign DNA in Cases of Oral
      Intercourse: a Female Perspective.
AB  - Saliva plus DNA from a suspect is commonly encountered in sexual assault cases on
      bodily swabs. However, without background knowledge, the weight of this evidence
      is unknown. It may indicate the presence of saliva resulting from cunnilingus, or
      it may represent indirect transfer. In this study, females who refrained from
      cunnilingus donated 43 items of underwear and 19 vaginal swabs. The samples were
      subjected to Phadebas((r)) , RSID(TM) -Saliva and mRNA profiling and were
      subsequently DNA-profiled to determine the prevalence of background saliva in the
      female population. The results report that 15.8% of females who refrained from
      cunnilingus were positive for saliva and a further 10.5% also had DNA from
      unknown source(s). These findings of the rate of indirect transfer were evaluated
      with the Bayesian approach, and it was found that the evidence of saliva plus a
      high foreign DNA source adds moderately strong support to the allegation of
      cunnilingus.

PMID- 26212905
TI  - Steric-Hindrance-Induced Regio- and Chemoselective Oxidation of Aromatic Amines.
AB  - Unusual regio- and chemoselective oxidation of aromatic amines hindered with
      ortho substituents (except -NH2, -NHCH3, and -OH) to the corresponding nitro
      compounds is described by use of nonanebis(peroxoic acid). The mechanistic
      investigation for selective oxidation of amines ortho-substituted with -NH2 or 
      OH showed the involvement of H-bonding between the ortho hydrogen of the adjacent
      -XH group (where X = NH, NR, or O) and an oxygen atom from the diperoxy acid.
      Various mono- and diamines are oxidized into corresponding mononitro derivatives
      in high yield and purity without employing any protection strategies. The
      protocol was also found to successful on the gram scale. 

PMID- 26212906
TI  - Sex estimation from modern American humeri and femora, accounting for sample
      variance structure.
AB  - OBJECTIVES: A new procedure for skeletal sex estimation based on humeral and
      femoral dimensions is presented, based on skeletons from the United States. The
      approach specifically addresses the problem that arises from a lack of variance
      homogeneity between the sexes, taking into account prior information about the
      sample's sex ratio, if known. MATERIAL AND METHODS: Three measurements useful for
      estimating the sex of adult skeletons, the humeral and femoral head diameters and
      the humeral epicondylar breadth, were collected from 258 Americans born between
      1893 and 1980 who died within the past several decades. RESULTS: For measurements
      individually and collectively, the probabilities of being one sex or the other
      were generated for samples with an equal distribution of males and females,
      taking into account the variance structure of the original measurements. The
      combination providing the best estimates correctly classifies 88.3% of the
      skeletons, with 10.8% considered unknown and 0.9% assigned to the wrong sex.
      DISCUSSION: Probabilities of correct assignments are a better means of
      categorizing individuals as male or female than the sectioning points commonly
      used in skeletal studies. That is because it is possible to estimate the
      observer's certainty that the individual represented by measured bones was one
      sex or the other. A computer program is available that simultaneously considers
      samples of unequal sex composition. It is useful when there is contextual
      information available about the nature of skeletal samples (e.g., a mass burial
      from a battle or genocide).

PMID- 26212907
TI  - Matrix-Stiffness-Regulated Inverse Expression of Kruppel-Like Factor 5 and
      Kruppel-Like Factor 4 in the Pathogenesis of Renal Fibrosis.
AB  - The proliferation of mouse proximal tubular epithelial cells in ex vivo culture
      depends on matrix stiffness. Combined analysis of the microarray and experimental
      data revealed that Kruppel-like factor (Klf)5 was the most up-regulated
      transcription factor accompanied by the down-regulation of Klf4 when cells were
      on stiff matrix. These changes were reversed by soft matrix via extracellular
      signal-regulated kinase (ERK) inactivation. Knockdown of Klf5 or forced
      expression of Klf4 inhibited stiff matrix-induced cell spreading and
      proliferation, suggesting that Klf5/Klf4 act as positive and negative regulators,
      respectively. Moreover, stiff matrix-activated ERK increased the protein level
      and nuclear translocation of mechanosensitive Yes-associated protein 1 (YAP1),
      which is reported to prevent Klf5 degradation. Finally, in vivo model of
      unilateral ureteral obstruction revealed that matrix stiffness-regulated
      Klf5/Klf4 is related to the pathogenesis of renal fibrosis. In the dilated
      tubules of obstructed kidney, ERK/YAP1/Klf5/cyclin D1 axis was up-regulated and
      Klf4 was down-regulated. Inhibition of collagen crosslinking by lysyl oxidase
      inhibitor alleviated unilateral ureteral obstruction-induced tubular dilatation
      and proliferation, preserved Klf4, and suppressed the ERK/YAP1/Klf5/cyclin D1
      axis. This study unravels a novel mechanism how matrix stiffness regulates
      cellular proliferation and highlights the importance of matrix stiffness
      modulated Klf5/Klf4 in the regulation of renal physiologic functions and fibrosis
      progression.

PMID- 26212908
TI  - Specific Lipopolysaccharide Serotypes Induce Differential Maternal and Neonatal
      Inflammatory Responses in a Murine Model of Preterm Labor.
AB  - Intrauterine inflammation is recognized as a key mediator of both normal and
      preterm birth but is also associated with neonatal neurological injury.
      Lipopolysaccharide (LPS) is often used to stimulate inflammatory pathways in
      animal models of infection/inflammation-induced preterm labor; however,
      inconsistencies in maternal and neonatal responses to LPS are frequently
      reported. We hypothesized that LPS serotype-specific responses may account for a
      portion of these inconsistencies. Four different Escherichia coli LPS serotypes
      (O111:B4, O55:B5, O127:B8, and O128:B12) were administered to CD1 mice via
      intrauterine injection at gestational day 16. Although control animals delivered
      at term 60 +/- 15 hours postinjection (p.i.), those administered with O111:B4
      delivered 7 +/- 2 hours p.i., O55:B5 delivered 10 +/- 3 hours p.i., O127:B8
      delivered 16 +/- 10 hours p.i., and O128:B12 delivered 17 +/- 2 hours p.i. (means
      +/- SD). A correlation between the onset of preterm labor and myometrial
      activation of the inflammatory transcription factor, activator protein 1, but not
      NF-kappaB was observed. Specific LPS serotypes induced differential activation of
      downstream contractile and inflammatory pathways in myometrium and neonatal pup
      brain. Our findings demonstrate functional disparity in inflammatory pathway
      activation in response to differing LPS serotypes. Selective use of LPS serotypes
      may represent a useful tool for targeting specific inflammatory response
      mechanisms in these models.

PMID- 26212909
TI  - Novel CARD11 Mutations in Human Cutaneous Squamous Cell Carcinoma Lead to
      Aberrant NF-kappaB Regulation.
AB  - NF-kappaB signaling plays a crucial role in regulating proliferation and
      differentiation in the epidermis. Alterations in the NF-kappaB pathway can lead
      to skin pathologies with a significant burden to human health such as psoriasis
      and cutaneous squamous cell carcinoma (cSCC). Caspase recruitment domain (CARD)
      containing scaffold proteins are key regulators of NF-kappaB signaling by
      providing a link between membrane receptors and NF-kappaB transcriptional
      subunits. Mutations in the CARD family member, CARD14, have been identified in
      patients with the inflammatory skin diseases psoriasis and pityriasis rubra
      pilaris. Here, we describe that the gene coding for another CARD scaffold
      protein, CARD11, is mutated in more than 38% of 111 cSCCs, and show that novel
      variants outside of the coiled-coil domain lead to constitutively activated NF
      kappaB signaling. CARD11 protein expression was detectable in normal skin and
      increased in all cSCCs tested. CARD11 mRNA levels were comparable with CARD14 in
      normal skin and CARD11 mRNA was increased in cSCC. In addition, we identified
      CARD11 mutations in peritumoral and sun-exposed skin, suggesting that CARD11
      mediated alterations in NF-kappaB signaling may be an early event in the
      development of cSCC.

PMID- 26212910
TI  - alphavbeta3 Integrins Mediate Flow-Induced NF-kappaB Activation, Proinflammatory
      Gene Expression, and Early Atherogenic Inflammation.
AB  - Endothelial cell interactions with transitional matrix proteins, such as
      fibronectin, occur early during atherogenesis and regulate shear stress-induced
      endothelial cell activation. Multiple endothelial cell integrins bind
      transitional matrix proteins, including alpha5beta1, alphavbeta3, and
      alphavbeta5. However, the role these integrins play in mediating shear stress
      induced endothelial cell activation remains unclear. Therefore, we sought to
      elucidate which integrin heterodimers mediate shear stress-induced endothelial
      cell activation and early atherogenesis. We now show that inhibiting alphavbeta3
      integrins (S247, siRNA), but not alpha5beta1 or alphavbeta5, blunts shear stress
      induced proinflammatory signaling (NF-kappaB, p21-activated kinase) and gene
      expression (ICAM1, VCAM1). Importantly, inhibiting alphavbeta3 did not affect
      cytokine-induced proinflammatory responses or inhibit all shear stress-induced
      signaling, because Akt, endothelial nitric oxide synthase, and extracellular
      regulated kinase activation remained intact. Furthermore, inhibiting alphav
      integrins (S247), but not alpha5 (ATN-161), in atherosclerosis-prone
      apolipoprotein E knockout mice significantly reduced vascular remodeling after
      acute induction of disturbed flow. S247 treatment similarly reduced early diet
      induced atherosclerotic plaque formation associated with both diminished
      inflammation (expression of vascular cell adhesion molecule 1, plaque macrophage
      content) and reduced smooth muscle incorporation. Inducible, endothelial cell
      specific alphav integrin deletion similarly blunted inflammation in models of
      disturbed flow and diet-induced atherogenesis but did not affect smooth muscle
      incorporation. Our studies identify alphavbeta3 as the primary integrin
      heterodimer mediating shear stress-induced proinflammatory responses and as a key
      contributor to early atherogenic inflammation. 

PMID- 26212913
TI  - ?

PMID- 26212911
TI  - Hepatocyte-Specific Expression of Human Lysosome Acid Lipase Corrects Liver
      Inflammation and Tumor Metastasis in lal(-/-) Mice.
AB  - The liver is a major organ for lipid synthesis and metabolism. Deficiency of
      lysosomal acid lipase (LAL; official name Lipa, encoded by Lipa) in mice (lal(-/
      )) results in enlarged liver size due to neutral lipid storage in hepatocytes and
      Kupffer cells. To test the functional role of LAL in hepatocyte, hepatocyte
      specific expression of human LAL (hLAL) in lal(-/-) mice was established by cross
      breeding of liver-activated promoter (LAP)-driven tTA transgene and (tetO)7-CMV
      hLAL transgene with lal(-/-) knockout (KO) (LAP-Tg/KO) triple mice. Hepatocyte
      specific expression of hLAL in LAP-Tg/KO triple mice reduced the liver size to
      the normal level by decreasing lipid storage in both hepatocytes and Kupffer
      cells. hLAL expression reduced tumor-promoting myeloid-derived suppressive cells
      in the liver of lal(-/-) mice. As a result, B16 melanoma metastasis to the liver
      was almost completely blocked. Expression and secretion of multiple tumor
      promoting cytokines or chemokines in the liver were also significantly reduced.
      Because hLAL is a secretory protein, lal(-/-) phenotypes in other compartments
      (eg, blood, spleen, and lung) also ameliorated, including systemic reduction of
      myeloid-derived suppressive cells, an increase in CD4(+) and CD8(+) T and B
      lymphocytes, and reduced B16 melanoma metastasis in the lung. These results
      support a concept that LAL in hepatocytes is a critical metabolic enzyme in
      controlling neutral lipid metabolism, liver homeostasis, immune response, and
      tumor metastasis. 

PMID- 26212912
TI  - Donor-specific anti-HLA antibodies in pediatric renal transplant recipients with
      creeping creatinine: Prevalence, histological correlations, and impact on patient
      and graft survival.
AB  - Donor-specific anti-HLA antibodies (DSA) causing CAMR are responsible for a high
      proportion of long-term graft failures after RTX. We studied the prevalence of
      DSA in RTX children biopsied for creeping Cr, its relationship with NA, and
      patient and graft survival according to histopathology. Between 2008 and 2013, 92
      children were biopsied at a median of 38 months post-RTX. At biopsy, the
      prevalence of DSA was 49% and C4d 70%. NA rate was 45%, higher in adolescents
      (60%). Most frequent diagnoses were CAMR (72%) and interstitial fibrosis with
      tubular atrophy (IFTA) (28%). Forty-five of 66 patients with CAMR (68%) had
      detectable DSA. Twenty-one DSA-negative patients with CAMR had histological
      damage (IFTA + C4d positivity). C4d was detected in 64 of 66 biopsies with CAMR.
      Recipients with IFTA alone had neither C4d, nor detectable DSA, and were
      adherent. Graft survival at five yr was 89% in patients with CAMR, 79% in those
      with CAMR + TCMR Banff I, 33% in those with CAMR + TCMR Banff II, and 96% in
      those with IFTA. ABMR and complement activation were frequent in children
      biopsied for creeping Cr. Recipients with DSA were more likely to be non-adherent
      and have CAMR or CAMR + TCMR and worse graft survival.

PMID- 26212914
TI  - ?

PMID- 26212915
TI  - ?

PMID- 26212916
TI  - ?

PMID- 26212917
TI  - ?

PMID- 26212918
TI  - ?

PMID- 26212919
TI  - ?

PMID- 26212920
TI  - ?

PMID- 26212921
TI  - ?

PMID- 26212922
TI  - ?

PMID- 26212924
TI  - SMPP: The Spreadsheet-Based MODFLOW Pre-Processor.

PMID- 26212923
TI  - Nutrient Composition and Anti-inflammatory Potential of a Prescribed Macrobiotic
      Diet.
AB  - Despite nutrient adequacy concerns, macrobiotic diets are practiced by many
      individuals with cancer and other life-threatening illnesses. This study compared
      the nutrient composition and inflammatory potential of a macrobiotic diet plan
      with national dietary recommendations and intakes from a nationally
      representative sample. Nutrient comparisons were made using the 1) macrobiotic
      diet plan outlined in the Kushi Institute's Way to Health; 2) recommended dietary
      allowances (RDA); and 3) National Health and Nutrition Examination Survey
      (NHANES) 2009-2010 data. Comparisons included application of the recently
      developed dietary inflammatory index (DII). Analyses focused on total calories,
      macronutrients, 28 micronutrients, and DII scores. Compared to NHANES data, the
      macrobiotic diet plan had a lower percentage of energy from fat, higher total
      dietary fiber, and higher amounts of most micronutrients. Nutrients often met or
      exceeded RDA recommendations, except for vitamin D, vitamin B12, and calcium.
      Based on DII scores, the macrobiotic diet was more anti-inflammatory compared to
      NHANES data (average scores of -1.88 and 1.00, respectively). Findings from this
      analysis of a macrobiotic diet plan indicate the potential for disease prevention
      and suggest the need for studies of real-world consumption as well as designing,
      implementing, and testing interventions based on the macrobiotic approach. 

PMID- 26212925
TI  - Lack of cardioprotection by single-dose magnesium prophylaxis on isoprenaline
      induced myocardial infarction in adult Wistar rats.
AB  - AIM: Magnesium (Mg(2+)) is effective in treating cardiovascular disorders such as
      arrhythmias and pre-eclampsia, but its role during myocardial infarction (MI)
      remains uncertain. In this study, we investigated the effects of Mg(2+)pre
      treatment on isoprenaline (ISO) -induced MI in vivo. METHODS: Rats divided into
      four groups were each pre-treated with either MgSO4 (270 mg/kg intraperitoneally)
      or an equivalent volume of physiological saline, prior to the ISO (67 mg/kg
      subcutaneously) or saline treatments. One day post-treatment, the
      electrocardiogram and left ventricular blood pressures were recorded. Infarcts
      were determined using 2,3,5-triphenyltetrazolium chloride staining, and serum
      markers of lipid peroxidation were measured with spectrophotometric assays.
      RESULTS: Mg(2+) pre-treatment neither altered the ISO-induced infarct size
      compared with ISO treatment alone (p > 0.05), nor reversed the low-voltage
      electrocardiogram or the prominent Q waves induced by ISO, despite a trend to
      decreased Q waves. Similarly, Mg(2+) did not prevent the ISO-induced decrease in
      peak left ventricular blood pressure or the decrease in minimal rate of pressure
      change. Mg(2+) did not reverse the ISO-induced gain in heart weight or loss of
      body weight. Neither ISO nor Mg(2+) altered the concentrations of lipid
      peroxidation markers 24 hours post MI induction. CONCLUSION: Although Mg(2+) had
      no detrimental effects on electrical or haemodynamic activity in ISO-induced MI,
      the lack of infarct prevention may detract from its utility in MI therapy.

PMID- 26212926
TI  - A Single Stereodynamic Center Modulates the Rate of Self-Assembly in a
      Biomolecular System.
AB  - Chirality is a property of asymmetry important to both physical and abstract
      systems. Understanding how molecular systems respond to perturbations in their
      chiral building blocks can provide insight into diverse areas such as
      biomolecular self-assembly, protein folding, drug design, materials, and
      catalysis. Despite the fundamental importance of stereochemical preorganization
      in nature and designed materials, the ramifications of replacing chiral centers
      with stereodynamic atomic mimics in the context of biomolecular systems is
      unknown. Herein, we demonstrate that replacement of a single amino acid
      stereocenter with a stereodynamic nitrogen atom has profound consequences on the
      self-assembly of a biomolecular system. Our results provide insight into how the
      fundamental biopolymers of life would behave if their chiral centers were not
      configurationally stable, highlighting the vital importance of stereochemistry as
      a pre-organizing element in biomolecular folding and assembly events. 

PMID- 26212928
TI  - Enantioselective Total Synthesis of (-)-Hosieine A.
AB  - The first total synthesis of (-)-hosieine A was accomplished and features an
      unprecedented nitroso-ene cyclization to construct the 2-azabicyclo[3.2.1]octane
      ring system. Phosphine-enabled stereoselective bromohydrination provided
      interesting mechanistic insights into the anti-Markovnikov process. Also
      noteworthy is the retention of stereochemistry at C9 in the facile radical
      debromination initiated by Et3 B/air. 

PMID- 26212927
TI  - Perspectives on next steps in classification of oro-facial pain - part 1: role of
      ontology.
AB  - The purpose of this study was to review existing principles of oro-facial pain
      classifications and to specify design recommendations for a new system that would
      reflect recent insights in biomedical classification systems, terminologies and
      ontologies. The study was initiated by a symposium organised by the International
      RDC/TMD Consortium Network in March 2013, to which the present authors
      contributed. The following areas are addressed: problems with current
      classification approaches, status of the ontological basis of pain disorders,
      insufficient diagnostic aids and biomarkers for pain disorders, exploratory
      nature of current pain terminology and classification systems, and problems with
      prevailing classification methods from an ontological perspective. Four
      recommendations for addressing these problems are as follows: (i) develop a
      hypothesis-driven classification structure built on principles that ensure to our
      best understanding an accurate description of the relations among all entities
      involved in oro-facial pain disorders; (ii) take into account the physiology and
      phenomenology of oro-facial pain disorders to adequately represent both domains
      including psychosocial entities in a classification system; (iii) plan at the
      beginning for field-testing at strategic development stages; and (iv) consider
      how the classification system will be implemented. Implications in relation to
      the specific domains of psychosocial factors and biomarkers for inclusion into an
      oro-facial pain classification system are described in two separate papers. 

PMID- 26212929
TI  - Evaluation of stair motion contributes to new insights into hip osteoarthritis
      related motion pathomechanics.
AB  - Stair motion in the presence of hip osteoarthritis (OA) has received less
      attention than level walking. Its more strenuous aspect may shed the light on
      different locomotor strategies when compared to walking. We, therefore, aimed to
      define stair motion features associated to hip OA and to evaluate whether these
      specific features would differ from level walking and better characterize the hip
      pathological condition. Principal component and linear discriminant analyses
      were, respectively, used as data reduction and classification techniques. Our
      study highlighted that most of stair motion features associated to hip OA were
      similar to the ones of walking. Stair descent presented with the lowest
      misclassification error rate, ranging from 12% to 19% (estimated by cross
      validation). But, features that may be considered as a mechanism to reduce demand
      on the hip abductors were found to be more important in the stair ascent
      condition. This was reflected by both, greater importance in the classification
      rule and variance compared with walking, that is, decreased hip internal rotation
      moment at mid-stance (72.50% vs. 57.63%) and increased trunk lateroflexion toward
      affected side (56.43% vs. 29.37%). This study emphasized the importance of
      investigating stair motion in hip osteoarthritic population by highlighting
      specific locomotor strategies.

PMID- 26212930
TI  - Diversity Analysis of Polyporus umbellatus in China Using Inter-simple Sequence
      Repeat (ISSR) Markers.
AB  - Polyporus (P.) umbellatus, an endangered medicinal fungus in China, is
      distributed throughout most areas of the country. Thirty-seven natural P.
      umbellatus samples collected from 12 provinces in China were subjected to the
      inter-simple sequence repeat (ISSR) assay to investigate the genetic diversity
      within and among the 11 natural populations. Nine ISSR primers selected from 100
      primers produced 88 discernible DNA bands, with 46 being polymorphic. The
      frequency of polymorphism varied from 19.57 to 93.48% with an average of 61.26%
      across all populations. At the population level, the within-population variance
      was much greater (92.04%) than the between-population variance (7.96%) as
      revealed by analysis of molecular variance. Eleven P. umbellatus populations were
      grouped into two major clusters, and the clustering pattern displayed four groups
      using the unweighted pair-group method with an arithmetic mean dendrogram.
      Principal coordinate analysis further indicated that the genetic diversity of P.
      umbellatus strains was unevenly distributed and displayed a clustered
      distribution pattern instead. Within these clusters, subgrouping (Henan and
      Hubei) and cluster II (Jilin and Heilongjiang) related to the geographic
      distribution were evident. The present study provides the first global overview
      of P. umbellatus diversity analysis in China, which may open up new opportunities
      in comparative genetic research on this medicinal fungus in other countries. 

PMID- 26212931
TI  - Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols.
AB  - Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora
      of conditions, with most approaches relying on the secretion of paracrine signals
      by MSC to modulate the immune system, promote wound healing, and induce
      angiogenesis. Hypoxia has been shown to affect MSC proliferation,
      differentiation, survival and secretory profile. Here, we investigate changes in
      the lipid composition of human bone marrow-derived MSC after exposure to hypoxia.
      Using mass spectrometry, we compared the lipid profiles of MSC derived from five
      different donors, cultured for two days in either normoxia (control) or hypoxia
      (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty
      acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the
      phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the
      secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin
      8, without affecting significantly their respective mRNA levels. Functionally,
      incubation of MSC in hypoxia with D609 inhibited the potential of the cells to
      promote migration of human endothelial cells in a wound/scratch assay. Hence, we
      show that hypoxia induces in MSC an increase of DG that may affect the angiogenic
      potential of these cells.

PMID- 26212932
TI  - Spin Crossover in [Fe(2-Picolylamine)3](2+) Adjusted by Organosulfonate Anions.
AB  - Three mononuclear spin crossover (SCO) compounds [Fe(2-pic)3].A2.Solv (A = m-ABS(
      ), Solv = MeOH, 1; A = p-ABS(-), 2; A = OTf(-), 3) were prepared and
      characterized magnetically and structurally (2-pic = 2-picolylamine, m-HABS = m
      aminobenzenesulfonic acid, p-HABS = p-aminobenzenesulfonic acid, HOTf =
      trifluoromethanesulfonic acid). Single-crystal X-ray analyses show that they are
      constructed from the charge-assisted hydrogen bonds between the 2-pic donors and
      the organosulfonate acceptors, forming the hydrogen-bonded three-dimensional
      networks for 1 and 2 and one-dimensional columns for 3. While the [Fe(2
      pic)3](2+) cations in compounds 1 and 2 are in the meridional (mer-)
      configuration, it has a facial (fac-) configuration in complex 3. Magnetic
      susceptibility measurements revealed the SCO transitions and the SCO properties
      in all three complexes are quite different. Compound 1 undergoes an abrupt SCO
      with critical temperatures T1/2? = 100 K and T1/2? = 103 K, while compound 2
      exhibits a gradual SCO with T1/2 = 218 K. Compound 3, with the fac-configuration,
      has an abrupt SCO transition accompanied by the structural phase transition with
      critical temperatures T1/2? = 333 K and T1/2? = 343 K. The SCO transitions were
      further confirmed by the detailed structural analyses of the coordination
      environments of the Fe(II) centers in both spin states and also by differential
      scanning calorimetry. Compared to the famous [Fe(2-pic)3].A2.Solv compounds in
      the literature, compound 2 has the highest transition temperature for the mer
      [Fe(2-pic)3](2+)-containing compounds, while compound 3 represents the first
      example of the structurally characterized compound of the fac-[Fe(2-pic)3](2+)
      motif showing SCO behavior. These results show that the organosulfonate anions
      are very promising to adjust the hydrogen-bonded structures of the SCO compounds
      and improve the SCO properties of those structures. 

PMID- 26212933
TI  - Determination of quality attributes in wax jambu fruit using NIRS and PLS.
AB  - The aim of this work was to develop an analytical method to predict total
      anthocyanins content (TAC) and total phenolic compounds (TPC) in intact wax jambu
      fruit [Syzygium malaccense (L.) Merryl et Perry] using near-infrared spectroscopy
      (NIRS) and partial least squares (PLS). The estimation accuracy was based on
      parameters such as root mean square error of prediction (RMSEP), correlation
      coefficients [calibration (rc) and prediction (rp) set] and ratio of performance
      to deviation (RPD). TAC, rp = 0.98, RMSEP = 9.0 mg L(-1) and RPD = 5.19 were
      attained using second derivative pre-treatment. TPC, rp = 0.94, RMSEP = 22.18 (mg
      gallic acid equivalents (GAE)/100g) and RPD = 3.27 (excellent accuracy) were also
      obtained using second derivative pre-treatment. These findings suggest that the
      NIRS and PLS algorithms can be used to determine TCA and TPC in intact wax jambu
      fruit.

PMID- 26212934
TI  - Stress during slaughter increases lipid metabolites and decreases oxidative
      stability of farmed rainbow trout (Oncorhynchus mykiss) during frozen storage.
AB  - The consequences of slaughter on the formation of lipid metabolites and oxidative
      stability of fish muscle during long term frozen storage (-10  degrees C) were
      evaluated using farmed rainbow trout killed by asphyxia in air or percussion. The
      level of major adenine nucleotides and their related compounds was determined in
      order to check the stress level during slaughter. Plasma lipid metabolites were
      studied through the determination of eicosanoids and docosanoids such as
      prostaglandins, leukotrienes, thromboxanes, isoprostanes, resolvins, hydroxides,
      hydroperoxides, coming from eicosapentaenoic (EPA), arachidonic (ARA), and
      docosahexaenoic (DHA) acids. In addition, lipid oxidative stability of fillets
      was monitored. Results revealed that stress during slaughter can greatly
      influence oxidative stress and oxidative stability of rainbow trout fillets. In
      fact, asphyxia, which was the most stressful, induced a higher production of some
      lipid mediators such as hydroperoxides and EPA-derived prostaglandins, such as 12
      HpHEPE/15-HpHEPE and PGD3/PGE3. As a consequence, fillets derived from
      asphyxiated fish were less stable in terms of oxidative stability and showed
      lower shelf-life.

PMID- 26212935
TI  - Effects of stearic acid and gamma irradiation, alone and in combination, on
      pasting properties of high amylose maize starch.
AB  - The effects of stearic acid and gamma irradiation on pasting properties of high
      amylose maize starch (HAMS) were studied. Stearic acid (0%, 1.5%, and 5%) was
      added to HAMS, and then irradiated at 0, 30, and 60 kGy before pasting. Stearic
      acid increased the paste viscosity of un-irradiated HAMS from 420 mPas to 557 and
      652 mPas for 1.5% and 5% stearic acid, respectively. This observation related
      well with the formation of type II amylose-lipid complexes, with melting
      temperatures of about 100-120  degrees C. Gamma irradiation (30 and 6 0kGy)
      reduced pasting viscosity of HAMS. Pasting of gamma irradiated HAMS resulted in
      the formation of type I amylose-lipid complexes, with melting temperatures and
      enthalpies ranging from 82 to 102  degrees C and 0.22 to 1.85 J/g, respectively.
      Stearic acid addition followed by irradiation creates means of producing
      different types of amylose-lipid complexes from HAMS for industrial utilization.

PMID- 26212936
TI  - Chemiluminescence determination of potassium bromate in flour based on flow
      injection analysis.
AB  - A novel and highly sensitive flow-injection chemiluminescence method for the
      determination of potassium bromate (KBrO3) has been developed. This method is
      based on the luminescence properties of the KBrO3-Na2SO3-quinine sulfate system
      in acid medium. Optimized experimental conditions and a possible mechanism were
      investigated. The relative chemiluminescence intensity responded linearly to the
      concentration of KBrO3 in the range of 7.054 * 10(-6)-1.008 * 10(-4) mol/L with a
      detection limit of 2.116 * 10(-6) mol/L. The relative standard deviation (RSD) at
      5.0 * 10(-5) mol/L KBrO3 (n = 12) was 2.3%. The proposed method was applied
      successfully to the determination of KBrO3 in flour.

PMID- 26212937
TI  - pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added
      phenolic antioxidants.
AB  - Influence of pH on the antioxidant activities of combinations of lettuce extract
      (LE) with quercetin (QC), green tea extract (GTE) or grape seed extract (GSE) was
      investigated for both reduction of Fremy's salt in aqueous solution using direct
      electron spin resonance (ESR) spectroscopy and in L-alpha-phosphatidylcholine
      liposome peroxidation assay measured following formation of conjugated dienes.
      All examined phenolic antioxidants showed increasing radical scavenging effect
      with increasing pH values by using both methods. QC, GTE and GSE acted
      synergistically in combination with LE against oxidation of peroxidating
      liposomes and with QC showing the largest effect. The pH dependent increase of
      the antioxidant activity of the phenols is due to an increase of their electron
      donating ability upon deprotonation and to their stabilization in alkaline
      solutions leading to polymerization reaction. Such polymerization reactions of
      polyphenolic antioxidants can form new oxidizable -OH moieties in their polymeric
      products resulting in a higher radical scavenging activity.

PMID- 26212938
TI  - Study on lipolysis-oxidation and volatile flavour compounds of dry-cured goose
      with different curing salt content during production.
AB  - The effect of dry-curing salt content (4% low salt (LS), 8% high salt (HS)) on
      lipolysis, lipid oxidation and volatile compounds in dry-cured goose was
      investigated in our study. The activities of acid lipase and neutral lipase
      increased during dry-curing, while phospholipase reached its maximum at the end
      of marinating. Lipoxygenase (LOX) and thiobarbituric acid reactive substances
      (TBARS) values increased during dry-curing and marinating then decreased during
      dry-ripening. Total free fatty acids (TFFA) increased at dry-curing and dry
      ripening points and decreased during marinating. Total peak area of lipids
      derived volatile compounds (TPALDVC) and total peak area increased during entire
      stages. Compared to LS, HS group has higher lipolytic and LOX activities, TBARS,
      TFFA, unsaturated fatty acids and TPALDVC. The higher TPALDVC in HS could be
      attributed to higher lipid hydrolysis and oxidation during processing. 

PMID- 26212939
TI  - Antioxidant and antimicrobial effects of kordoi (Averrhoa carambola) fruit juice
      and bamboo (Bambusa polymorpha) shoot extract in pork nuggets.
AB  - Pork nuggets with 'very good' acceptability was processed by incorporating kordoi
      (Averrhoa carambola) fruit juice and bamboo (Bambusa polymorpha) shoot extract,
      and their physical, chemical, microbiological and sensorial characteristics were
      evaluated during 35 days storage under refrigeration. Addition of kordoi fruit
      juice (4%) and bamboo shoot extract (6%) had a significant effect on the pH,
      moisture, protein, fat, fiber, instrumental color values and texture profiles of
      nuggets. Nuggets with juice and extract had significantly lower TBARS values
      towards the end of the storage period compared to the control. Microbial and
      sensory qualities of nuggets were significantly improved by the addition of juice
      and extract. Incorporation of juice and extract at 4% and 6% levels,
      respectively, increased the storage life of pork nuggets by at least two weeks,
      i.e. from 21 days to 35 days at 4 +/- 1  degrees C compared to the control.

PMID- 26212940
TI  - Development of an analytical method to measure insoluble and soluble starch in
      sugarcane and sweet sorghum products.
AB  - A rapid research method using microwave-assisted probe ultrasonication was
      developed to quantify total, insoluble, and soluble starch in various sugar crop
      products. Several variables affecting starch solubilisation were evaluated, (1)
      heating method, (2) boiling time, (3) probe ultrasonication time, (4) water loss,
      (5) concentration, (6) sample colour, and (7) sample. The optimised method
      solubilises < 40,000 ppm insoluble starch with microwave-assisted sonication in 6
      min, has acceptable precision (<6% CV), accuracy (? 95%), uses a corn starch
      reference, and incorporates a colour blank to remove contribution from natural
      colourants found in industrial samples. This method was validated using factory
      samples and found applicable to sugarcane and sweet sorghum bagasse (3% CV),
      mixed juices (2%), massecuites (4%), molasses (7%), and raw sugars (12%), 100%
      satisfactory performance z-scores were also obtained. Total starch values
      obtained with this method were significantly higher than those measured using
      other methods presently accepted by the sugar industry.

PMID- 26212941
TI  - Flutriafol and pyraclostrobin residues in Brazilian green coffees.
AB  - The aim of this work was to monitor flutriafol and pyraclostrobin residues in
      Brazilian green coffees. More than 10,000 samples were analyzed. The pesticides
      were extracted using the QuEChERS method and analyzed by LC-MS/MS. The validated
      method is fast, with 5 min runs, and efficient, as precision and accuracy showed
      RSD no greater than 5% and recoveries within the 88-119% range. LOQ for
      flutriafol and pyraclostrobin were 0.005 mg/kg. The results of the analyzed
      samples showed that the percentage of nonconformities regarding flutriafol
      increased throughout the years, with over 1200 samples (11.8%). On the other
      hand, just 15 samples (0.15%) presented residues above 10 MUg/kg for
      pyraclostrobin. Considering that flutriafol is a toxic and carcinogenic
      pesticide, as well as the increase in the number of irregularities throughout the
      years, it becomes important to implement public actions to assure consumer
      safety.

PMID- 26212942
TI  - Determination of carbohydrates in honey and milk by capillary electrophoresis in
      combination with graphene-cobalt microsphere hybrid paste electrodes.
AB  - A graphene-cobalt microsphere (CoMS) hybrid paste electrode was developed for the
      determination of carbohydrates in honey and milk in combination with capillary
      electrophoresis (CE). The performance of the electrodes was demonstrated by
      detecting mannitol, sucrose, lactose, glucose, and fructose after CE separation.
      The five analytes were well separated within 9 min in a 40 cm long capillary at a
      separation voltage of 12 kV. The electrodes exhibited pronounced electrocatalytic
      activity, lower detection potentials, enhanced signal-to-noise characteristics,
      and higher reproducibility. The relation between peak current and analyte
      concentration was linear over about three orders of magnitude. The proposed
      method had been employed to determine lactose in bovine milk and glucose and
      fructose in honey with satisfactory results. Because only electroactive
      substances in the samples could be detected on the paste electrode, the
      electropherograms of both food samples were simplified to some extent.

PMID- 26212943
TI  - Application of HPLC-DAD after SPE/QuEChERS with ZrO2-based sorbent in d-SPE clean
      up step for pesticide analysis in edible oils.
AB  - In this study, the solid-phase extraction/quick, easy, cheap, effective, rugged
      and safe (SPE/QuEChERS) technique was adapted to develop a simple sample
      treatment for multi-residue pesticide analysis of edible oils. The proposed
      method is based on liquid-liquid partitioning with acetonitrile followed by
      dispersive solid phase extraction using zirconia-coated silica particles for
      extract purification. To evaluate the described method, 21 pesticides belonging
      to different chemical classes were analysed using high performance liquid
      chromatography with diode-array detection (HPLC-DAD). For validation purposes,
      recovery studies were performed at 75 ng g(-1), 125 ng g(-1), 250 ng g(-1), 500
      ng g(-1) and 1000 ng g(-1) levels. Recoveries were over the range of 50-130% for
      most of the analytes, with relative standard deviations less than 15% being
      observed. HPLC-DAD provided suitable linearity, precision and accuracy. The
      validated method was successfully applied to the analysis of edible oil samples
      selected from the market.

PMID- 26212944
TI  - Characterization of free and conjugated phenolic compounds in fruits of selected
      wild plants.
AB  - A gas chromatography-mass spectrometric (GC-MS) method was utilized for the
      separation, and systematic characterization of phenolic compounds as
      trimethylsilyl derivatives in fruits of wild plants including Olive, Jujube and
      Common Fig. Both the free and conjugate phenolic acids (rarely determined before
      and several are reported first time here) were characterized. A baseline
      separation of the 20 phenolics was achieved in 25 min with standard calibration
      curves linear over the concentration range from the detection limits to 20
      MUg/mL. Total of fourteen phenolic acids were identified in wild Olive fruit,
      eight in wild Jujube fruit and ten in wild Common Fig fruit, out of which 2,4
      dihydroxybenzoic acid and trans-cinnamic acid were dominant in these fruits with
      concentration of 87.02, 5.25 and 14.16 mg/kg and 32.43, 5.77 and 11.70 mg/kg (dry
      weight), respectively. The results of this study support the utilization of the
      tested wild fruits as a potential source of valuable phenolics for functional
      food and nutraceutical applications.

PMID- 26212945
TI  - Effect of soybean aging on the quality of soymilk, firmness of tofu and optimum
      coagulant concentration.
AB  - This study investigated the influence of soybean aging (cultivars Coodetec 214
      and BRS 267) on the physicochemical properties of soymilk and tofu. Two aging
      conditions were adopted: accelerated aging (84% relative humidity and 30  degrees
      C, up to 9 months) and natural aging (ambient temperature and relative humidity,
      up to 18 months) and a control condition (47% relative humidity, -20  degrees C).
      Tofu was coagulated with MgSO4. Optimum coagulant concentration (OCC) decreased
      with increasing coagulation temperature and soybean aging time. OCC showed
      positive correlation with total solids, protein, ash, Ca, Mg and P contents of
      soymilk. The products showed, in general, reduced color parameters (L(*) and h
      degrees ), proteins, lipids, carbohydrates, ash, Ca, Mg, P and total solids
      (except in the tofu) and firmness (tofu) with increasing aging time. Tofu yields
      decreased with accelerated aging time.

PMID- 26212946
TI  - Generation of chlorine by-products in simulated wash water.
AB  - Free chlorine (FC) reacting with organic matter in wash water promotes the
      formation of chlorine by-products. This study aims to evaluate the dynamic impact
      of FC and organic load on the generation of haloacetic acids (HAAs) and
      trihalomethanes (THMs) in simulated wash water. Lettuce juice was sequentially
      added into FC solution with FC periodically replenished. Water samples were
      collected after each lettuce juice addition to measure water qualities and
      determine HAAs and THMs using US-Environmental-Protection-Agency (EPA) methods.
      Concentrations of 88-2103 MUg/l of total HAAs and 20.79-859.47 MUg/l of total
      THMs were detected during the study. Monobromoacetic, tribromoacetic,
      chlorodibromoacetic and trichloroacetic acid were the major HAAs components.
      Chloroform (trichloromethane) was the primary THMs present. A significant
      correlation of HAAs with chemical oxygen demand and THMs with FC was observed.
      Results indicated that optimizing wash water sanitizing systems to limit organic
      matters and maintain minimal effective FC concentration is critical.

PMID- 26212947
TI  - Application of metal-organic frameworks for purification of vegetable oils.
AB  - Reported here is the synthesis of aluminum-, zinc- and titanium-containing metal
      organic frameworks based on terephthalic acid and an investigation on the
      possibility of using these compounds as adsorbents for the purification of
      unrefined vegetable oils. It is found that aluminum-, zinc- and titanium
      containing metal-organic frameworks improve the physicochemical properties of
      unrefined vegetable oils (more pleasant taste and odor) due to the binding of
      free fatty acids and peroxide compounds. It is established that the synthesized
      materials are more effective in these respects as compared with traditional
      adsorbents. An adsorption mechanism of free fatty acids and peroxides is
      proposed. Last but not least, the used MOF can be easily recycled at least five
      times, via solvent washing. 

PMID- 26212948
TI  - Changes in apoptotic factors and caspase activation pathways during the
      postmortem aging of beef muscle.
AB  - The pathway of apoptosis (effector caspase activation) in beef muscle cells was
      investigated by examining the expression of apoptotic factors during postmortem
      (PM) storage of beef muscle. Results showed that caspase-3 could be activated in
      PM beef muscle. The expression of cytochrome c increased in the cytosolic
      fraction but significantly decreased in the mitochondrial fraction in the early
      PM period, which demonstrated that cytochrome c was released from mitochondrion
      to cytoplasm. The expression of the anti-apoptotic factor Bcl-2 did not show any
      visible change, and that of pro-apoptotic factor Bax increased during PM storage.
      Expression of the heat-shock protein Hsp27 significantly decreased with increased
      PM time. These results demonstrated that the mitochondrial pathway was one of the
      apoptosis pathways in PM beef muscle and that Bax and Hsp27 were two key
      regulation factors in apoptosis in PM beef muscle. 

PMID- 26212949
TI  - Colorimetric and fluorescence quenching aptasensors for detection of streptomycin
      in blood serum and milk based on double-stranded DNA and gold nanoparticles.
AB  - Antibiotic residues in animal foodstuffs are of great concern to consumers. In
      this study, fluorescence quenching and colorimetric aptasensors were designed for
      detection of streptomycin based on aqueous gold nanoparticles (AuNPs) and double
      stranded DNA (dsDNA). In the absence of streptomycin, aptamer/FAM-labeled
      complementary strand dsDNA is stable, resulting in the aggregation of AuNPs by
      salt and an obvious color change from red to blue and strong emission of
      fluorescence. In the presence of streptomycin, aptamer binds to its target and
      FAM-labeled complementary strand adsorbs on the surface of AuNPs. So the well
      dispersed AuNPs remain stable against salt-induced aggregation with a wine-red
      color and the fluorescence of FAM-labeled complimentary strand is efficiently
      quenched by AuNPs. The colorimetric and fluorescence quenching aptasensors showed
      excellent selectivity toward streptomycin with limit of detections as low as 73.1
      and 47.6 nM, respectively. The presented aptasensors were successfully used to
      detect streptomycin in milk and serum.

PMID- 26212950
TI  - Authentication of canned fish packing oils by means of Fourier transform infrared
      spectroscopy.
AB  - The authentication of packing oil from commercial canned tuna and other tuna-like
      fish species was examined by means of attenuated total reflection Fourier
      transform infrared spectroscopy (ATR-FTIR) and chemometrics. Using partial least
      squares discriminant analysis (PLS-DA), it was possible to differentiate olive
      oil from seed oils. Discrimination of olive oil from high-oleic sunflower oil was
      possible, despite the latter having a degree of unsaturation more similar to
      olive oil than to sunflower oil. However, in the samples analyzed, sunflower oil
      could not be differentiated clearly from those labeled with the generic term
      "vegetable oil". Furthermore, the authentication of extra virgin olive oil,
      although more difficult, could be achieved using ATR-FTIR spectroscopy. The
      method could be applied regardless of fish type, without interference from fish
      lipids. 

PMID- 26212951
TI  - Iron binding to caseins in the presence of orthophosphate.
AB  - As adding >5mM ferric chloride to sodium caseinate solutions results in protein
      precipitation, the effects of orthophosphate (0-64 mM) addition to sodium
      caseinate solution (2% w/v protein) on iron-induced aggregation of the caseins
      were studied at pH 6.8. Up to 20mM ferric chloride could be added to sodium
      caseinate solution containing 32 mM orthophosphate without any protein
      precipitation. The addition of iron to sodium caseinate solution containing
      orthophosphate reduced the diffusible phosphorus content in a concentration
      dependent manner. Added iron appeared to interact simultaneously with
      phosphoserine on the caseins and inorganic phosphorus. The relative sizes of the
      casein aggregates were governed by the concentration of orthophosphate and the
      aggregates consisted of all casein fractions, even at the lowest level of ferric
      chloride addition (5mM). It is hypothesised that the addition of iron to caseins
      in the presence of orthophosphate results in the formation of colloidal
      structures involving casein-iron-orthophosphate interactions.

PMID- 26212952
TI  - Real-time monitoring of process parameters in rice wine fermentation by a
      portable spectral analytical system combined with multivariate analysis.
AB  - A portable and low-cost spectral analytical system was developed and used to
      monitor real-time process parameters, i.e. total sugar content (TSC), alcohol
      content (AC) and pH during rice wine fermentation. Various partial least square
      (PLS) algorithms were implemented to construct models. The performance of a model
      was evaluated by the correlation coefficient (Rp) and the root mean square error
      (RMSEP) in the prediction set. Among the models used, the synergy interval PLS
      (Si-PLS) was found to be superior. The optimal performance by the Si-PLS model
      for the TSC was Rp = 0.8694, RMSEP = 0.438; the AC was Rp = 0.8097, RMSEP =
      0.617; and the pH was Rp = 0.9039, RMSEP = 0.0805. The stability and reliability
      of the system, as well as the optimal models, were verified using coefficients of
      variation, most of which were found to be less than 5%. The results suggest this
      portable system is a promising tool that could be used as an alternative method
      for rapid monitoring of process parameters during rice wine fermentation.

PMID- 26212953
TI  - Feasibility of combining spectra with texture data of multispectral imaging to
      predict heme and non-heme iron contents in pork sausages.
AB  - To precisely determine heme and non-heme iron contents in meat product, the
      feasibility of combining spectral with texture features extracted from
      multispectral imaging data (405-970 nm) was assessed. In our study, spectra and
      textures of 120 pork sausages (PSs) treated by different temperatures (30-80 
      degrees C) were analyzed using different calibration models including partial
      least squares regression (PLSR) and LIB support vector machine (Lib-SVM) for
      predicting heme and non-heme iron contents in PSs. Based on a combination of
      spectral and textural features, optimized PLSR models were obtained with
      determination coefficient (R(2)) of 0.912 for heme and of 0.901 for non-heme iron
      prediction, which demonstrated the superiority of combining spectra with texture
      data. Results of satisfactory determination and visualization of heme and non
      heme iron contents indicated that multispectral imaging could serve as a feasible
      approach for online industrial applications in the future.

PMID- 26212954
TI  - Inhibition of hardy kiwifruit (Actinidia aruguta) ripening by 1
      methylcyclopropene during cold storage and anticancer properties of the fruit
      extract.
AB  - Hardy kiwifruits (Actinidia arguta) were treated with 20 MUl/l 1
      methylcyclopropene (1-MCP) for 16 h at 10  degrees C and subsequently stored at 1
      +/- 0.5  degrees C. Anticancer properties of the fruit extracts were tested
      against five different human cancer cells. The hardy kiwifruits, without 1-MCP
      treatment, showed increases in both respiration and ethylene production rates
      during fruit storage. The 1-MCP treatment remarkably inhibited fruit ripening by
      reducing respiration and ethylene production. Fruits with the 1-MCP treatment
      could be stored for up to 5 weeks by maintaining higher fruit firmness, ascorbic
      acid and total phenolic contents compared to the control. The hardy kiwifruit
      extracts showed anti-proliferative effects to Hep3B and HeLa cells but not to
      HT29, HepG2 and LoVo cells. These results suggest that the application of 1-MCP
      at harvest effectively delayed the ripening process of the fruits, and the fruit
      extract had beneficial effects for the prevention of human cancer growth.

PMID- 26212955
TI  - Speciation of As(III) and As(V) in fruit juices by dispersive liquid-liquid
      microextraction and hydride generation-atomic fluorescence spectrometry.
AB  - A sensitive method was developed to speciate and quantify As(III) and As(V) in
      fruit juices. At pH 3.0, As(III) and ammonium pyrrolidine dithiocarbamate (APDC)
      formed a complex, which was extracted into CCl4 by dispersive liquid-liquid
      microextraction (DLLME) and subsequently quantified by hydride generation-atomic
      fluorescence spectrometry (HG-AFS). After As(V) was reduced by thiosulphate at pH
      1.7-1.8, total inorganic arsenic (iAs) was determined following the same protocol
      and As(V) was calculated from the difference. Interference from methylarsonic
      acid (MMA) was managed at <10% by controlling the pH of the reduction reaction.
      This procedure achieved 1.2 MUg L(-1) limit of detection (3sigma) and 92-102%
      recovery at 10 MUg L(-1), and is applicable to most fruit juices except certain
      pear juice that may contain considerable MMA.

PMID- 26212956
TI  - In vitro digestion of short-dough biscuits enriched in proteins and/or fibres
      using a multi-compartmental and dynamic system (2): Protein and starch
      hydrolyses.
AB  - The influence of protein and/or fibre enrichment on the nutritional properties of
      biscuits was studied in terms of proteolysis and amylolysis. Biscuits were
      digested using a multi-compartmental and dynamic system that simulates the main
      physiological digestive functions of the upper tract of healthy adult humans: the
      TIM-1. A control biscuit and three biscuits enriched in proteins and/or fibres
      were digested under the same conditions. Samples were collected in each
      compartment of the TIM-1 (stomach, duodenum, jejunum and ileum) at different
      times of digestion and analysed in terms of proteolysis and amylolysis. Results
      indicate that both formulation and processing impacted the digestive fate of the
      biscuits. Incorporating proteins or fibres in biscuits lowered or delayed
      proteolysis. Moreover a protein-plus-fibre additional or synergic effect was
      observed. Biscuits enriched in proteins and/or fibres displayed a higher
      amylolysis degree than the control biscuit, probably due to lower starch amounts
      and higher gelatinization degrees. 

PMID- 26212957
TI  - The complexity of condensed tannin binding to bovine serum albumin--An isothermal
      titration calorimetry study.
AB  - Isothermal titration calorimetry was applied to study the binding of purified
      proanthocyanidin oligomers to bovine serum albumin (BSA). The molecular weight of
      the proanthocyanidin oligomer had a major impact on its binding to BSA. The
      calculated change in enthalpy (DeltaH) and association constant (Ka) became
      greater as the oligomer size increased then plateaued at the heptameric oligomer.
      These results support a model for precipitation of proteins by proanthocyanidin
      where increased oligomer size enhanced the opportunity for cross linkages between
      proteins ultimately forming sediment-able complexes. The authors suggest tannin
      binding to proteins is opportunistic and involves multiple sites, each with a
      different Ka and DeltaH of binding. The DeltaH of binding comprises both an
      endothermic hydrophobic interaction and exothermic hydrogen bond component. This
      suggests the calculated entropy value (DeltaS) for tannin-protein interactions is
      subject to a systematic error and should be interpreted with caution. 

PMID- 26212958
TI  - Middle infrared stabilization of individual rice bran milling fractions.
AB  - The aim of this study was to determine the composition and hydrolytic
      deterioration behavior of rice bran fractions which were obtained individually
      from different rice whitening mills. Additionally, stabilization of these bran
      fractions individually with middle infrared radiation and its effects on the
      contents of tocopherols and gamma-oryzanol were investigated. FFA content of the
      crude and stabilized bran fractions that were obtained from the last whitening
      and polishing steps was higher either in the beginning or in the end of the
      storage compared to the others obtained in the first steps of whitening.
      Stabilization at 700 W infrared (medium-wave) power for 7.0 min provided 90 days
      of shelf life without a notable change in FFA content of rice bran fraction which
      was obtained from the first whitening step. Total tocopherol and gamma-oryzanol
      contents of stabilized rice bran fractions were higher than their crude
      counterparts.

PMID- 26212959
TI  - Extraction optimization of pepsin-soluble collagen from eggshell membrane by
      response surface methodology (RSM).
AB  - Response surface methodology (RSM) was used to investigate the effect of
      extraction-process variables on pepsin-soluble collagen (PSC) from eggshell
      membrane. A central composite design (CCD) was employed for experimental design
      and analysis of the results to obtain the best possible combination of NaOH
      concentration (X1: 0.4-1.2 mol/l), alkali treatment time (X2: 6-30 h), enzyme
      concentration (X3: 15-75 U/mg) and hydrolysis time (X4: 12-60 h) for maximum PSC
      extraction. The experimental data obtained were fitted to a second-order
      polynomial equation using multiple regression analysis and analyzed by
      appropriate statistical methods. According to the results, optimum extraction
      conditions were as follows: NaOH concentration of 0.76 mol/l, alkali treatment
      time of 18 h, enzyme concentration of 50 U/mg and hydrolysis time of 43.42 h. The
      experimental extraction yield under optimal conditions was found to be 30.049%,
      which is in good agreement with the predicted value of 30.054%.

PMID- 26212960
TI  - Mineral decline due to modernization of food habits.
AB  - Calcium and other micronutrients are essential for health and well-being. Dairy
      products are the main sources of calcium in western countries. In most regions of
      Asia, the consumption of these products is limited due to the lactose intolerance
      and costs. A major contributor to the micronutrients intake in this region is the
      consumption of small fish, such as anchovies. Traditionally, dried anchovies are
      consumed as a whole body. Recently, an increasingly popular method of eating
      anchovies has been to eat it in a cleaned, eviscerated form. This brief
      communication highlights how "modernization" of food habits may have
      unintentional nutritional consequences. A minor change in the dietary habits of
      eating cleaned anchovies may lead to a reduction in micronutrients intake. This
      reinforces the need for caution when we modernize our traditional eating habits. 

PMID- 26212961
TI  - Size measuring techniques as tool to monitor pea proteins intramolecular
      crosslinking by transglutaminase treatment.
AB  - In this work, techniques for monitoring the intramolecular transglutaminase cross
      links of pea proteins, based on protein size determination, were developed.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles of
      transglutaminase-treated low concentration (0.01% w/w) pea albumin samples,
      compared to the untreated one (control), showed a higher electrophoretic
      migration of the major albumin fraction band (26 kDa), reflecting a decrease in
      protein size. This protein size decrease was confirmed, after DEAE column
      purification, by dynamic light scattering (DLS) where the hydrodynamic radius of
      treated samples appears to be reduced compared to the control one.

PMID- 26212962
TI  - Phospholipase A1-catalyzed hydrolysis of soy phosphatidylcholine to prepare l
      alpha-glycerylphosphorylcholine in organic-aqueous media.
AB  - This study aimed to optimize the preparation of L-alpha-glycerylphosphorylcholine
      (l-alpha-GPC) via phospholipase A1 (Lecitase Ultra)-catalyzed hydrolysis of soy
      phosphatidylcholine (PC). The reaction was performed in n-hexane-water biphasic
      media in a stirred batch reactor, and modeling and optimization were conducted
      using response surface methodology. Optimal conditions to completely hydrolyze PC
      to L-alpha-GPC were: temperature, 50  degrees C; reaction time, 30 h; water
      content, 69 g/100 g of PC weight; and enzyme loading, 13 g/100 g of PC weight.
      The optimal n-hexane-to-water ratio in the medium was 5.8:1 (v/v), and 21.3g of
      PC was treated as the substrate in 100 mL of the medium. L-alpha-GPC with purity
      99.3 g/100 g was obtained from the reaction products after diethyl ether
      extraction and silica column chromatography. These findings suggest that the use
      of n-hexane-water media increases the productivity of l-alpha-GPC compared to the
      aqueous media used in enzymatic reaction systems in other published studies.

PMID- 26212963
TI  - Inhibitory kinetics and mechanism of kaempferol on alpha-glucosidase.
AB  - alpha-Glucosidase is a therapeutic target for diabetes mellitus, and alpha
      glucosidase inhibitors play a vital role in the treatments for the disease. As a
      kind of potentially safer alpha-glucosidase inhibitor, flavonoids have attached
      much attention currently. In this study, kaempferol was found to show a notable
      inhibition activity on alpha-glucosidase in a mixed-type manner with IC50 value
      of (1.16 +/- 0.04) * 10(-5) mol L(-1). Analyses of fluorescence, circular
      dichroism and Fourier transform infrared spectra indicated that kaempferol bound
      to alpha-glucosidase with high affinity which was mainly driven by hydrogen bonds
      and van der Waals forces, and this binding resulted in conformational alteration
      of alpha-glucosidase. Further molecular docking study validated the experimental
      results. It was proposed that kaempferol may interact with some amino acid
      residues located within the active site of alpha-glucosidase, occupying the
      catalytic center of the enzyme to avoid the entrance of p-nitrophenyl-alpha-D
      glucopyranoside and ultimately inhibiting the enzyme activity.

PMID- 26212964
TI  - Reliability of the DeltaECN42 limit and global method for extra virgin olive oil
      purity assessment using different analytical approaches.
AB  - Two data elaboration approaches for evaluating olive oils authenticity were
      compared: (I) determination of the difference between the theoretical and actual
      amounts of triacylglycerols with partition number 42 (DeltaECN42 ? |0.2|); and
      (II) the global method, which considers also partition numbers 44 and 46
      (returning a "correct"/"not correct" result). Analysis of 31 genuine extra virgin
      olive oil samples was performed using different analytical methods, namely liquid
      chromatography (LC) coupled with a refractive index detector (RID) and LC coupled
      with a mass spectrometry (MS), and the results compared. Several false positives
      were highlighted using the DeltaECN42 limit with both instrumental approaches.
      The global method algorithm returned "correct" results for all the samples
      analysed (except two that gave no results) with LC-MS; on the other hand, 10
      false positives were obtained elaborating data deriving from NARP-LC-RID
      analysis.

PMID- 26212965
TI  - Lactose- and cellobiose-derived branched trisaccharides and a sucrose-containing
      trisaccharide produced by acceptor reactions of Weissella confusa dextransucrase.
AB  - Dextran-producing Weissella have received significant attention. However, except
      for maltose, the acceptor reactions of Weissella dextransucrases with different
      sugars have not been investigated. The action of recombinant Weissella confusa
      VTT E-90392 dextransucrase was tested with several potential acceptors,
      particularly, analogs lactose and cellobiose. The major acceptor products of both
      disaccharides were identified as branched trisaccharides, with a glucosyl residue
      alpha-(1 -> 2)-linked to the acceptor's reducing end. An additional product,
      isomelezitose (6(Fru)-alpha-Glcp-sucrose), was also produced when using lactose
      as an acceptor. This is the first report of the synthesis of isomelezitose by a
      dextransucrase. The NMR spectra of the three trisaccharides were fully assigned,
      and their structures were confirmed by selective enzymatic hydrolysis. The
      trisaccharides prepared from (13)C6(glc) sucrose and lactose were analyzed by ESI
      MS(n), and the fragmentation patterns of these compounds were characterized.

PMID- 26212966
TI  - Performance of a protein extracted from potatoes for fining of white musts.
AB  - In this study, the potentiality of Patatin (P), a protein extracted from potato,
      as must fining agent was investigated on musts obtained from two South Italy
      grape cultivars (Falanghina and Greco). Besides P, fining agents as bentonite (B)
      and potassium caseinate (C) were assayed at different concentrations. The rate of
      sedimentation, the decline of turbidity during time, the absorbance at 420 nm,
      the GRP (grape reaction products) and hydroxycinnamic acids (HCA) concentrations
      were determined. The comparative trials showed that P is a suitable fining agent
      to prevent browning and decrease haze during must settling because its effect on
      grape phenolics, brown pigments and turbidity is comparable and/or better than
      that detected for C. Its use as single fining agent or in combination with B
      depends on must characteristics.

PMID- 26212967
TI  - Near Infrared Spectroscopy (NIRS) for the determination of the milk fat fatty
      acid profile of goats.
AB  - Milk fatty acid (FA) composition is important for the goat dairy industry because
      of its influence on cheese properties and human health. The aim of the present
      work was to evaluate the feasibility of NIRS reflectance (oven-dried milk using
      the DESIR method) and transflectance (liquid milk) analysis to predict milk FA
      profile and groups of fats in milk samples from individual goats. NIRS analysis
      of milk samples allowed to estimate FA contents and their ratios and indexes in
      fat with high precision and accuracy. In general, transflectance analysis gave
      better or similar results than reflectance mode. Interestingly, NIRS analysis
      allowed direct prediction of the Atherogenicity and Thrombogenicity indexes,
      which are useful for the interpretation of the nutritional value of goat milk.
      Therefore, the calibrations obtained in the present work confirm the viability of
      NIRS as a fast, reliable and effective analytical method to provide nutritional
      information of milk samples. 

PMID- 26212968
TI  - A rapid qualitative and quantitative evaluation of grape berries at various
      stages of development using Fourier-transform infrared spectroscopy and
      multivariate data analysis.
AB  - Fourier transform (FT) near-infrared (NIR) and attenuated total reflection (ATR)
      FT mid-infrared (MIR) spectroscopy were used to qualitatively and quantitatively
      analyse Vitis vinifera L. cv Sauvignon blanc grape berries. FT-NIR and ATR FT-MIR
      spectroscopy, coupled with spectral preprocessing and multivariate data analysis
      (MVDA), provided reliable methods to qualitatively assess berry samples at five
      distinct developmental stages: green, pre-veraison, veraison, post-veraison and
      ripe (harvest), without any prior metabolite extraction. Compared to NIR spectra,
      MIR spectra provided more reliable discrimination between the berry samples from
      the different developmental stages. Interestingly, ATR FT-MIR spectra from fresh
      homogenized berry samples proved more discriminatory than spectra from frozen
      homogenized berry samples. Different developmental stages were discriminated by
      principal component analysis (PCA) and orthogonal partial least squares
      discriminant analysis (OPLS-DA). In order to generate partial least squares (PLS)
      models from the MIR/NIR spectral datasets; the major sugars (glucose and
      fructose) and organic acids (malic acid, succinic acid and tartaric acid) were
      separated and quantified by high performance liquid chromatography (HPLC) and the
      data used as a reference dataset. PLS regression was used to develop calibration
      models to predict the concentration of the major sugars and organic acids in the
      berry samples from different developmental stages. Our data show that infrared
      (IR) spectroscopy could provide a rapid, reproducible and cost-effective
      alternative to the chromatographic analysis of the sugar and organic acid
      composition of grape berries at various developmental stages, using small sample
      volumes and requiring limited sample preparation. This provides scope and support
      for the possible development of hand-held devices to assess quality parameters in
      field-settings in real-time and non-destructively using IR technologies. 

PMID- 26212969
TI  - Ultrasound-assisted magnetic solid-phase extraction for the determination of some
      transition metals in Orujo spirit samples by capillary electrophoresis.
AB  - Ultrasound-assisted magnetic solid-phase extraction coupled to capillary
      electrophoresis was optimized for the preconcentration and determination of
      Zn(II), Cu(II), Mn(II) and Cd(II) as their complexes with 1,10-phenanthroline
      (Phen). Both pre- and on-capillary complexations were employed to obtain stable
      metal-Phen complexes. The parameters that have an influence on the
      electrophoretic separation and the MSPE process were studied and optimized using
      different experimental designs. Metals were extracted from 10 mL of sample at pH
      5 using 3mg of magnetic particles functionalized with carboxylic groups. The
      metals were eluted as metal-Phen complexes and analyzed by capillary
      electrophoresis. The method showed low limits of detection for metals 0.49-2.19
      MUg L(-1), and high preconcentration factors, 39-44, The efficiencies of the
      extraction method were in the range 77.1-87.5% and the precision (RSD < 10%) and
      accuracy were between 98.2% and 101.6%. The method was applied to the
      determination of the aforementioned metals in Galician Orujo spirit samples.

PMID- 26212970
TI  - Validation of an HPLC method for direct measurement of steviol equivalents in
      foods.
AB  - Steviol glycosides are intense natural sweeteners used in foods and beverages.
      Their acceptable daily intake, expressed as steviol equivalents, is set at 0-4
      mg/kg body weight. We report the development and validation of a RP-HPLC method
      with fluorometric detection of derivatized isosteviol, formed by acid hydrolysis
      of steviol glycosides. Dihydroisosteviol was used as an internal standard. Using
      this method, the amount of steviol equivalents in commercial steviol glycoside
      mixtures and different foods can be directly quantified. The method was
      successfully tested on strawberry jam, low-fat milk, soft drink, yogurt and a
      commercial mixture of steviol glycosides. Calibration curves were linear between
      0.01 and 1.61 mM steviol equivalents, with a quantification limit of 0.2 nmol.
      The % RSD of intra-day precision varied between 0.4% and 4%, whereas inter-day
      precision varied between 0.4% and 5%, for high and medium concentrations, and
      between 3% and 8% for low concentrations. Accuracy of the analysis varied between
      99% and 115%.

PMID- 26212971
TI  - A mass spectrometry method for the determination of the species of origin of
      gelatine in foods and pharmaceutical products.
AB  - Gelatine is a component of a wide range of foods. It is manufactured as a by
      product of the meat industry from bone and hide, mainly from bovine and porcine
      sources. Accurate food labelling enables consumers to make informed decisions
      about the food they buy. Since labelling currently relies heavily on due
      diligence involving a paper trail, there could be benefits in developing a
      reliable test method for the consumer industries in terms of the species origin
      of gelatine. We present a method to determine the species origin of gelatines by
      peptide mass spectrometry methods. An evaluative comparison is also made with
      ELISA and PCR technologies. Commercial gelatines were found to contain undeclared
      species. Furthermore, undeclared bovine peptides were observed in commercial
      injection matrices. This analytical method could therefore support the food
      industry in terms of determining the species authenticity of gelatine in foods. 

PMID- 26212972
TI  - Effect of fatty acids on functional properties of normal wheat and waxy wheat
      starches: A structural basis.
AB  - The effects of three saturated fatty acids on functional properties of normal
      wheat and waxy wheat starches were investigated. The complexing index (CI) of
      normal wheat starch-fatty acid complexes decreased with increasing carbon chain
      length. In contrast, waxy wheat starch-fatty acid complexes presented much lower
      CI. V-type crystalline polymorphs were formed between normal wheat starch and
      three fatty acids, with shorter chain fatty acids producing more crystalline
      structure. FTIR and Raman spectroscopy presented the similar results with XRD.
      The formation of amylose-fatty acid complex inhibited granule swelling,
      gelatinization progression, retrogradation and pasting development of normal
      wheat starch, with longer chain fatty acids showing greater inhibition.
      Amylopectin can also form complexes with fatty acids, but the amount of complex
      was too little to be detected by XRD, FTIR, Raman and DSC. As a consequence,
      small changes were observed in the functional properties of waxy wheat starch
      with the addition of fatty acids. 

PMID- 26212973
TI  - Development of a mushroom powder Certified Reference Material for calcium,
      arsenic, cadmium and lead measurements.
AB  - Isotope dilution mass spectrometry and standard addition techniques were
      developed for the analysis of four elements (Ca, As, Cd and Pb) in a mushroom
      powder material. Results from the validated methods were compared to those of
      other national metrology institutes in the CCQM-K89 intercomparisons and the
      results were in excellent agreement with the reference values. The same methods
      were then used for the assignment of reference values to a mushroom powder
      Certified Reference Material (CRM). The certified values obtained for Ca, As, Cd
      and Pb were 1.444 +/- 0.099 mg/g, 5.61 +/- 0.59 mg/kg, 1.191 +/- 0.079 mg/kg and
      5.23 +/- 0.94 mg/kg, respectively. The expanded measurement uncertainties were
      obtained by combining the uncertainty contributions from characterization (uchar)
      and between-bottle homogeneity (ubb).

PMID- 26212974
TI  - Proanthocyanidin screening by LC-ESI-MS of Portuguese red wines made with
      teinturier grapes.
AB  - Proanthocyanidins (PAs) are one of the most important polyphenolic compounds in
      wine. Among PAs, prodelphinidin (PD) dimers and trimers have not been widely
      detected in wines due to the lack of available commercial standards and the
      difficulty to detect and isolate them from natural sources. LC-ESI-MS (liquid
      chromatography-electrospray ionization-mass spectrometry) with the right
      chromatographic conditions has proven to be a powerful tool for PAs detection and
      identification in complex samples. This technique has been applied to an
      exhaustive study of PA composition of two Portuguese red wines made with
      teinturier grapes, especially for the identification of PD dimers and trimers.
      Tandem mass spectrometry (MS/MS) with ion trap provided additional information
      about the structures of these compounds through the fragmentation patterns of the
      pseudomolecular ions. A LC-ESI-MS method was optimized and 41 different compounds
      were found. Among them are included 8 PD dimers and 13 PD trimers. 

PMID- 26212975
TI  - Detailed analyses of fresh and dried maqui (Aristotelia chilensis (Mol.) Stuntz)
      berries and juice.
AB  - In this study, a detailed chemical characterization of nutritionally-relevant,
      quality-determining constituents in dried and fresh fruits as well as juices of
      maqui (Aristotelia chilensis (Mol.) Stuntz) is provided. A total of 8
      glycosylated anthocyanins was characterized in maqui fruits, being composed of
      differently substituted cyanidin and delphinidin derivatives. During processing
      into juice, a substantial loss in total anthocyanin contents (TAC) was observed.
      TAC values were also reduced after drying of maqui berries. Likewise, the
      browning index (BI) of fresh fruits increased during processing. Being composed
      of flavonol glycosides and ellagic acids, 17 non-anthocyanin phenolics were
      characterized in all maqui samples. Besides characterizing phenolic compounds,
      antioxidant activities, total phenolics, major sugars, non-volatile organic
      acids, minerals and trace elements were quantitated. Moreover, total lipid
      contents and the fruits' mainly unsaturated fatty acid profiles are reported. The
      presented results indicate the high potential of maqui as so far under-utilized
      but extremely pigment-rich "superfruit". 

PMID- 26212976
TI  - Effects of cold atmospheric gas phase plasma on anthocyanins and color in
      pomegranate juice.
AB  - The aim of the study was to evaluate effects of cold atmospheric gas phase plasma
      on anthocyanins and color in pomegranate juice. Outcomes of plasma treatment were
      observed at different operating conditions: (i) treatment time (3, 5, 7 min),
      (ii) treated juice volume (3, 4, 5 cm(3)), and (iii) gas flow (0.75, 1, 1.25
      dm(3)/min). The greatest anthocyanin stability was found at: 3 min treatment
      time, 5 cm(3) sample volume, and 0.75 dm(3)/min gas flow. Plasma treatment
      yielded higher anthocyanin content from 21% to 35%. Multivariate analysis showed
      that total color change was not associated with sample volume and treatment time,
      however it declined with increased gas flow. The change of color increased in
      comparison treated vs. untreated pomegranate juice. Constructed mathematical
      equation confirmed that increase of anthocyanin content increased with gas flow,
      sample volume and change in color. In summary, this study showed that plasma
      treatment had positive influences on anthocyanins stability and color change in
      cloudy pomegranate juice.

PMID- 26212977
TI  - Evaluation of the contamination of spirits by polycyclic aromatic hydrocarbons
      using ultrasound-assisted emulsification microextraction coupled to gas
      chromatography-mass spectrometry.
AB  - The concentration of twelve polycyclic aromatic hydrocarbons (PAHs), included in
      the list of priority pollutants, in different spirits has been obtained by means
      of a rapid and sensitive method based on gas chromatography and mass spectrometry
      (GC-MS). The environmentally friendly ultrasound-assisted emulsification
      microextraction (USAEME) technique allowed the easy and effective
      preconcentration of the PAHs from the sample matrices. Several parameters
      affecting the extraction efficiency, such as the nature and volume of the
      extractant solvent, and the addition of salt, as well as the sonication
      parameters were investigated and optimized. The absence of matrix effects under
      the optimized conditions allowed the sample quantification against aqueous
      standards. Detection limits ranged between 1.8 and 6.3 ng L(-1), depending on the
      compound. Different spirit samples were successfully analyzed using the proposed
      method, and contents of up to 0.9 MUg L(-1) were found. Relative recoveries at
      fortified levels of 0.2 and 1 MUg L(-1) were in the range 84-118%.

PMID- 26212978
TI  - Enzyme-assisted extraction and identification of antioxidative and alpha-amylase
      inhibitory peptides from Pinto beans (Phaseolus vulgaris cv. Pinto).
AB  - Antioxidant and alpha-amylase inhibitor peptides were successfully extracted from
      Pinto bean protein isolate (PBPI) using Protamex. A factorial design experiment
      was conducted and the effects of extraction time, pH and temperature were
      studied. pH 7.5, extraction time of 1h, S/E ratio of 10 (w/w) and temperature of
      50  degrees C gave the highest antioxidant activities (i.e., ABTS scavenging
      activity (53.3%) and FRAP value (3.71 mM)), whereas pH 6.5 with the same
      extraction time, S/E ratio and temperature, gave the highest alpha-amylase
      inhibitory activity (57.5%). It was then fractioned using membrane
      ultrafiltration with molecular weight cutoffs of 100, 50, 30, 10 and 3 kDa.
      Peptide fraction <3 kDa, which exhibited the highest antioxidant activities
      (i.e., ABTS (42.2%) and FRAP (0.81 mM)) and alpha-amylase inhibitory activity
      (62.1%), was then subjected to LCMS and MS/MS analyses. Six sequences were
      identified for antioxidant peptides, whereas seven peptides for alpha-amylase
      inhibitor.

PMID- 26212979
TI  - Macroporous resin purification of peptides with umami taste from soy sauce.
AB  - In this study, the performance and separation characteristics of four macroporous
      resins for purifying umami peptides from soy sauce were examined. Results showed
      that the resins could separate the peptides of soy sauce, and the particle
      diffusion kinetics model was suitable for describing the whole exothermic (DeltaH
      < 43 kJ/mol) adsorption process on the SP-825 and HP-20 resins, while the pseudo
      second-order kinetics model accurately described the XAD-16 and HP-2 MGL resins.
      Furthermore, the adsorption processes of the peptides followed the Freundlich
      model. The XAD-16 resin was the most effective resin for the enrichment of
      peptides due to its high adsorption and total desorption capacities.
      Interestingly, the umami peptides were enriched in the deionized water fraction.
      This study provides new insights into exploring performance and separation
      characteristics of macroporous resins on soy sauce, and indicated that peptide
      may be the contributor to the umami taste in Chinese soy sauce.

PMID- 26212980
TI  - Quantitative mass spectrometric analysis of dipeptides in protein hydrolysate by
      a TNBS derivatization-aided standard addition method.
AB  - The aim of this study was to establish, through a standard addition method, a
      convenient quantification assay for dipeptides (GY, YG, SY, YS, and IY) in
      soybean hydrolysate using 2,4,6-trinitrobenzene sulfonate (TNBS) derivatization
      aided LC-TOF-MS. Soybean hydrolysate samples (25.0 mg mL(-1)) spiked with target
      standards were subjected to TNBS derivatization. Under the optimal LC-MS
      conditions, five target dipeptides derivatized with TNBS were successfully
      detected. Examination of the standard addition curves, with a correlation
      coefficient of r(2) > 0.979, provided a reliable quantification of the target
      dipeptides, GY, YG, SY, YS, and IY, in soybean hydrolysate to be 424 +/- 20, 184
      +/- 9, 2188 +/- 199, 327 +/- 16, and 2211 +/- 133 MUg g(-1) of hydrolysate,
      respectively. The proposed LC-MS assay is a reliable and convenient assay method,
      with no interference from matrix effects in hydrolysate, and with no requirement
      for the use of an isotope labeled internal standard.

PMID- 26212981
TI  - Mercury accumulation in Yellowfin tuna (Thunnus albacares) with regards to muscle
      type, muscle position and fish size.
AB  - The concentrations and relationships between individual mercury species and total
      mercury were investigated in different muscle parts and sizes of Yellowfin tuna
      (Thunnus albacares). Fourteen Yellowfin tuna caught in the South Atlantic off the
      coast of South Africa had an average total Hg (tHg) concentration of 0.77 mg/kg
      wet weight. No differences were detected (p > 0.05) in tHg, MethylHg (MeHg) or
      inorganic Hg (iHg) accumulation among the four white muscle portions across the
      carcass, but both tHg and iHg were found in higher concentrations (p < 0.001) in
      dark muscle than white muscle. Positive linear correlations with fish weight were
      found for both tHg (r = 0.79, p < 0.001) and MeHg (r = 0.75, p < 0.001)
      concentrations. A prediction model was formulated to calculate toxic MeHg
      concentrations from measured tHg concentrations and fish weight (cMeHg = 0.073 +
      1.365 . tHg-0.008 . w). As sampling sites and subsampling methods could affect
      toxicity measurements, we provide recommendations for sampling guidelines.

PMID- 26212982
TI  - Models based on ultraviolet spectroscopy, polyphenols, oligosaccharides and
      polysaccharides for prediction of wine astringency.
AB  - Astringency elicited by tannins is usually assessed by tasting. Alternative
      methods involving tannin precipitation have been proposed, but they remain time
      consuming. Our goal was to propose a faster method and investigate the links
      between wine composition and astringency. Red wines covering a wide range of
      astringency intensities, assessed by sensory analysis, were selected. Prediction
      models based on multiple linear regression (MLR) were built using UV
      spectrophotometry (190-400 nm) and chemical analysis (enological analysis,
      polyphenols, oligosaccharides and polysaccharides). Astringency intensity was
      strongly correlated (R(2) = 0.825) with tannin precipitation by bovine serum
      albumin (BSA). Wine absorbances at 230 nm (A230) proved more suitable for
      astringency prediction (R(2) = 0.705) than A280 (R(2) = 0.56) or tannin
      concentration estimated by phloroglucinolysis (R(2) = 0.59). Three variable
      models built with A230, oligosaccharides and polysaccharides presented high R(2)
      and low errors of cross-validation. These models confirmed that polysaccharides
      decrease astringency perception and indicated a positive relationship between
      oligosaccharides and astringency.

PMID- 26212983
TI  - Evaluation of bromine and iodine content of milk whey proteins combining
      digestion by microwave-induced combustion and ICP-MS determination.
AB  - The bromine and iodine content of whey protein concentrate (WPC), hydrolysate
      (WPH), and isolate (WPI) was evaluated combining microwave-induced combustion
      (MIC) digestion with inductively coupled plasma mass spectrometry (ICP-MS)
      determination. MIC digestion allowed the decomposition of up to 500 mg of samples
      using diluted NH4OH solution (25 mmol L(-1)) for absorption of analytes, assuring
      the compatibility with ICP-MS determination. Accuracy was evaluated using milk
      powder certified reference material (NIST 8435) with good agreements for Br and I
      (102% and 105%, respectively). For Br and I, the limit of quantification obtained
      by ICP-MS was 7 and 281 times lower in comparison with ion chromatography
      determination, respectively. Iodine could be enriched in whey protein production
      and up to 70% of the tolerable upper intake level was found, thus revealing the
      need to monitor it in whey proteins. On the other hand, the concentration of Br
      was below its acceptable daily intake.

PMID- 26212984
TI  - Accurate determination of ochratoxin A in Korean fermented soybean paste by
      isotope dilution-liquid chromatography tandem mass spectrometry.
AB  - Ochratoxin A (OTA), a naturally occurring mycotoxin, has been frequently detected
      in doenjang, a traditional fermented soybean paste, when it is fermented under
      improper conditions. Reliable screening of OTA in traditional fermented soybean
      paste (doenjang) is a special food-safety issue in Korea. Our laboratory, the
      National Metrology Institute of Korea, established an isotope dilution-liquid
      chromatography tandem mass spectrometry (ID-LC/MS/MS) method as a higher-order
      reference method to be used for SI-traceable value-assignment of OTA in certified
      reference materials (CRMs). (13)C20-OTA was used as an internal standard. Sample
      preparation conditions and LC/MS measurement parameters were optimised for this
      purpose. The analytical method was validated by measuring samples fortified with
      OTA at various levels. Repeatability and reproducibility studies showed that the
      ID-LC/MS/MS method is reliable and reproducible within 2% relative standard
      deviation. The analytical method was applied to determine OTA in various
      commercial doenjang products and home-made doenjang products. 

PMID- 26212985
TI  - Effect of Se treatment on glucosinolate metabolism and health-promoting compounds
      in the broccoli sprouts of three cultivars.
AB  - Broccoli sprouts are natural functional foods for cancer prevention because of
      their high glucosinolate (GSL) content and high selenium (Se) accumulation
      capacity. The regulation mechanism of Se on GSL metabolism in broccoli sprouts
      was explored. In particular, the effects of Se treatment (100 MUmol/L selenite
      and selenate) on the Se, sulfur (S), glucosinolate and sulforaphane contents;
      myrosinase activity and health-promoting compounds (ascorbic acid, anthocyanin,
      total phenolics and flavonoids) of three, 5 day old, cultivars were investigated.
      The treatment did not influence the total GSL and ascorbic acid contents;
      significantly increased the myrosinase activity and sulforaphane, anthocyanin and
      flavonoids contents; and decreased the total phenolics content. The increase in
      sulforaphane during early growth can be primarily attributed to the increased
      myrosinase activity caused by Se treatment. Broccoli sprouts with suitable
      selenite and selenate concentrations, in the early growth days, could be
      desirable for improved human health.

PMID- 26212987
TI  - Determination of phthalates in food packing materials by electrokinetic
      chromatography with polymeric pseudostationary phase.
AB  - Polymeric pseudostationary phase (PSP), formed by random copolymer poly (stearyl
      methacrylate-co-methacrylic acid) (P(SMA-co-MAA)), was used in electrokinetic
      chromatography (EKC) to separate 15 kinds of phthalates (PAEs). The organic
      solvent modifier is a key factor for the separation of PAEs. Without organic
      solvents, only four kinds of PAEs with smaller molecular weight could be
      separated in the running buffer containing 1% P(SMA-co-MAA). The other eleven
      kinds of PAEs with larger molecular weight could be separated within 25 min by
      adding 40% (v/v) methanol and 2% (v/v) 1-butanol in the running buffer. The
      linear ranges of 15 kinds of PAEs were between 2 and 200mg/L, and the limit of
      detection based on the ratio of signal to noise of 3 were between 1 and 3mg/L.
      The method was applied to determination of PAEs in 6 kinds of food packing
      materials. The recoveries were between 81% and 118% with the RSD less than 4%.

PMID- 26212986
TI  - A novel fluorescence polarization assay for determination of penicillin G in
      milk.
AB  - Detection of penicillin G in milk is of interest because of the wide use of this
      antibiotic in livestock. Current analytical methods used to quantify the
      penicillin G in milk are based on HPLC, mass spectrometry and electrophoresis.
      These methodologies are time-consuming and require trained personnel. In
      addition, it is not easy to envisage the development of a portable device for in
      situ analyses based on these methods. We present a novel sensing approach for
      detecting the presence of penicillin G in milk. The proposed method is based
      penicillin G conjugate labeled with red-emitting dye with properly produced anti
      penicillin G antibodies. The results obtained suggest our method could be applied
      directly in milk without interference from other substances. The limit of
      detection of the method was 1.0 nmol/L, which is much less than the required MRL
      in EU regulations (12.0 nmol/L).

PMID- 26212988
TI  - Polyphenols rich fraction from Geoffroea decorticans fruits flour affects key
      enzymes involved in metabolic syndrome, oxidative stress and inflammatory
      process.
AB  - Geoffroea decorticans (chanar), is widely distributed throughout Northwestern
      Argentina. Its fruit is consumed as flour, arrope or hydroalcoholic beverage. The
      chanar fruits flour was obtained and 39 phenolic compounds were tentatively
      identified by HPLC-MS/MS(n). The compounds comprised caffeic acid glycosides,
      simple phenolics (protocatechuic acid and vanillic acid), a glycoside of vanillic
      acid, p-coumaric acid and its phenethyl ester as well as free and glycosylated
      flavonoids. The polyphenols enriched extract with and without gastroduodenal
      digestion inhibited enzymes associated with metabolic syndrome, including alpha
      amylase, alpha-glucosidase, lipase and hydroxyl methyl glutaryl CoA reductase.
      The polyphenolic extract exhibited antioxidant activity by different mechanisms
      and inhibited the pro-inflammatory enzymes (ciclooxygenase, lipoxygenase and
      phospholipase A2). The polyphenolic extract did not showed mutagenic effect by
      Ames test against Salmonella typhimurium TA98 and TA100 strains. These findings
      add evidence that chanar fruit flour may be considered a functional food with
      preventive properties against diseases associated with oxidative stress,
      inflammatory mediators and metabolic syndrome. 

PMID- 26212989
TI  - Characterization of main primary and secondary metabolites and in vitro
      antioxidant and antihyperglycemic properties in the mesocarp of three biotypes of
      Pouteria lucuma.
AB  - Pouteria lucuma is an Andean fruit from pre-Incas' times highly appreciated due
      to its characteristic flavor and taste in its homeland. We characterized the
      primary (e.g., sugars and organic acids), and secondary (e.g., phenolics and
      carotenoids) and in vitro antioxidant and antihyperglycemic properties of
      Rosalia, Montero and Leiva 1 lucuma biotypes. Significant differences were found
      in these metabolites and functional properties related to biotype and ripeness
      stage. Results showed significant amounts of sugars (119.4-344 mg total sugars g(
      1)DW) and organic acids (44.4-30.0 mg g(-1)DW) and functional associated
      compounds such as ascorbic acid (0.35-1.07 mg g(-1)DW), total phenolics (0.7-61.6
      mg GAE g(-1)DW) and total carotenoids (0.22-0.50 mg beta-carotene g(-1)DW).
      Important in vitro antioxidant and antihyperglycemic properties were found and
      provide the base for the standardization of lucuma harvest and postharvest
      focused not only on the enhancement of sensory but functional properties.

PMID- 26212990
TI  - Comparison of enzymatic and acid hydrolysis of bound flavor compounds in model
      system and grapes.
AB  - Four synthesized terpenyl-beta-D-glycopyranosides (geranyl, neryl, citronellyl,
      myrtenyl) were subjected to enzymatic (AR 2000, pH 5.5) and acid (citric buffer,
      pH 2.5) hydrolysis. Decrease of glycosides was measured by HPLC and the volatiles
      released--by comprehensive gas chromatography-mass spectrometry (GC * GC-ToF-MS).
      Enzymatic hydrolysis performed for 21 h yielded 100% degree of hydrolysis for all
      glycosides but citronellyl (97%). Degree of acid hydrolysis was highly dependent
      on type of aglycone and the conditions. The highest degree was achieved for
      geraniol, followed by citronellol and nerol. Myrtenylo-beta-D-glycopyranoside was
      the most resistant glycoside to hydrolysis. Acid hydrolysis degree was also
      related to temperature/time combination, the highest being for 100  degrees C and
      2 h. In a result of enzymatic hydrolysis 85-91% of total peak areas was terpene
      aglycone, whereas for acid hydrolysis the area of released terpene aglycone did
      not exceed 1.3% of total peak area indicating almost complete
      decomposition/transformation of terpenyl aglycone.

PMID- 26212991
TI  - Effect of fortification with parsley (Petroselinum crispum Mill.) leaves on the
      nutraceutical and nutritional quality of wheat pasta.
AB  - This study examines the nutraceutical (phenolics content, antioxidant activity,
      biological activity) and nutritional potential (starch and protein digestibility)
      of wheat pasta supplemented with 1-4% of powdered parsley leaves. Compared to the
      control, the potentially bioaccessible fraction of pasta fortified with 4%
      parsley leaves was characterized by 67% increased phenolics content, a 146%
      higher antiradical ability and 220% additional reducing power. Elevation of these
      parameters in fortified pasta was accompanied by an augmentation of its
      antiproliferative effect on carcinoma cells, which confirms their biological
      relevance. Supplementation of pasta had no significant effect on starch
      digestibility, while negatively affecting protein digestibility (a reduction by
      about 20% for pasta with a 4% supplement). Electrophoretic and chromatographic
      analyses indicated the presence of phenolic interactions with proteins and/or
      digestive enzymes. Fortification improved the nutraceutical and nutritional
      potential of the studied pasta; however, the final effect is made by many
      factors, including phenolics-food matrix interactions. 

PMID- 26212992
TI  - Evaluation and application of microwave-assisted extraction and dispersive liquid
      liquid microextraction followed by high-performance liquid chromatography for the
      determination of polar heterocyclic aromatic amines in hamburger patties.
AB  - This study developed an analytical method based on microwave-assisted extraction
      and dispersive liquid-liquid microextraction followed by high-performance liquid
      chromatography for the determination of three polar heterocyclic aromatic amines
      from hamburger patties. Effective parameters controlling the performance of the
      microextraction process, such as the type and volume of extraction and disperser
      solvents, microwave time, nature of alkaline aqueous solution, pH and salt
      amount, were optimized. The calibration graphs were linear in the range of 1-200
      ng g(-1), with a coefficient of determination (R(2)) better than 0.9993. The
      relative standard deviations (RSD) for seven analyses were between 3.2% and 6.5%.
      The recoveries of those compounds in hamburger patties were from 90% to 105%.
      Detection limits were between 0.06 and 0.21 ng g(-1). A comparison of the
      proposed method with the existing literature demonstrates that it is a simple,
      rapid, highly selective and sensitive, and it gives good enrichment factors and
      detection limits for determining HAAs in real hamburger patties samples.

PMID- 26212993
TI  - Evaluation of different drying techniques on the nutritional and biofunctional
      properties of a traditional fermented sheep milk product.
AB  - The purpose of this study was to evaluate the effect of solar and freeze drying
      techniques on the physicochemical, nutritional and biofunctional properties of
      salted or unsalted Jameed from fermented sheep milk product. The highest yield of
      Jameed was obtained via the salted-solar drying process. As measured by
      colorimetry, salted freeze-dried Jameed showed improved consumer characteristics
      in terms of increased lightness and decreased red and yellow color components.
      When unsalted Jameed was prepared by solar or freeze drying, additional major
      peptide bands were detected by SDS-PAGE treatments as compared to the solar or
      freeze drying of the salted Jameed. Use of salt in the preparation of solar dried
      Jameed also led to the highest ACE inhibitory activities whereas antioxidant
      activity was lowest in unsalted solar dried Jameed. The study findings indicate
      that both greater yield and better overall nutritional and biofunctional
      properties were associated with solar dried salted Jameed. 

PMID- 26212994
TI  - Development and validation of an APCI-MS/GC-MS approach for the classification
      and prediction of Cheddar cheese maturity.
AB  - Headspace techniques have been extensively employed in food analysis to measure
      volatile compounds, which play a central role in the perceived quality of food.
      In this study atmospheric pressure chemical ionisation-mass spectrometry (APCI
      MS), coupled with gas chromatography-mass spectrometry (GC-MS), was used to
      investigate the complex mix of volatile compounds present in Cheddar cheeses of
      different maturity, processing and recipes to enable characterisation of the
      cheeses based on their ripening stages. Partial least squares-linear discriminant
      analysis (PLS-DA) provided a 70% success rate in correct prediction of the age of
      the cheeses based on their key headspace volatile profiles. In addition to
      predicting maturity, the analytical results coupled with chemometrics offered a
      rapid and detailed profiling of the volatile component of Cheddar cheeses, which
      could offer a new tool for quality assessment and accelerate product development.

PMID- 26212995
TI  - Effects of preharvest applications of methyl jasmonate and chitosan on
      postharvest decay, quality and chemical attributes of Fragaria chiloensis fruit.
AB  - Fragaria chiloensis fruit has a short postharvest life mainly due to its rapid
      softening. In order to improve its postharvest life, preharvest applications of
      methyl jasmonate (MeJA) and chitosan were evaluated during postharvest storage at
      room temperature. The quality and chemical parameters, and protection against
      decay were evaluated at 0, 24, 48 and 72 h of storage from fruits of two
      subsequent picks (termed as first harvest and second harvest). In general, fruits
      treated with MeJA and chitosan maintained higher levels of fruit firmness,
      anthocyanin, and showed significant delays in decay incidence compared to control
      fruit. MeJA-treated fruits exhibited a greater lignin content and SSC/TA ratio,
      and delayed decay incidences. Instead, chitosan-treated fruits presented higher
      antioxidant capacity and total phenol content. In short, both the elicitors were
      able to increase the shelf life of fruits as evidenced by the increased levels of
      lignin and anthocyanin, especially of the second harvest.

PMID- 26212996
TI  - Selenium species in selenium fortified dietary supplements.
AB  - This article presents a study of dietary supplements available on the Polish
      market. The supplements comprised a large group of products with selenium content
      declared by the producer. The study involved determination of dissolution time
      under different conditions and solubility as well as content and speciation of
      selenium. The total content was determined as well as organic selenium and the
      inorganic forms Se(IV) and Se(VI). The organic selenium content was calculated as
      the difference between total Se and inorganic Se. The values obtained were
      compared with producers' declarations. The work is the first such study of
      selenium supplements available on the market of an EU Member State. 

PMID- 26212997
TI  - Magnetically separable polymer (Mag-MIP) for selective analysis of biotin in food
      samples.
AB  - This work presents an efficient method for the preparation of magnetic
      nanoparticles modified with molecularly imprinted polymers (Mag-MIP) through core
      shell method for the determination of biotin in milk food samples. The functional
      monomer acrylic acid was selected from molecular modeling, EGDMA was used as
      cross-linking monomer and AIBN as radical initiator. The Mag-MIP and Mag-NIP were
      characterized by FTIR, magnetic hysteresis, XRD, SEM and N2-sorption
      measurements. The capacity of Mag-MIP for biotin adsorption, its kinetics and
      selectivity were studied in detail. The adsorption data was well described by
      Freundlich isotherm model with adsorption equilibrium constant (KF) of 1.46 mL g(
      1). The selectivity experiments revealed that prepared Mag-MIP had higher
      selectivity toward biotin compared to other molecules with different chemical
      structure. The material was successfully applied for the determination of biotin
      in diverse milk samples using HPLC for quantification of the analyte, obtaining
      the mean value of 87.4% recovery.

PMID- 26212998
TI  - Concurrent measurement of cellular turbidity and hemoglobin to evaluate the
      antioxidant activity of plants.
AB  - In past decades, a multitude of analytical methods for measuring antioxidant
      activity of plant extracts has been developed. However, when using methods to
      determine hemoglobin released from human erythrocytes treated with ginger
      extracts, we found hemoglobin concentrations were significantly higher than in
      untreated control samples. This suggests in the presence of antioxidants that
      measuring hemoglobin alone is not sufficient to determine hemolysis. We show
      concurrent measurement of erythrocyte concentration and hemoglobin is essential
      in such assays, and describe a new protocol based on simultaneous measurement of
      cellular turbidity and hemoglobin. 

PMID- 26212999
TI  - Trace matrix solid phase dispersion using a molecular sieve as the sorbent for
      the determination of flavonoids in fruit peels by ultra-performance liquid
      chromatography.
AB  - A simple, rapid, and highly selective trace matrix solid phase dispersion (MSPD)
      technique, coupled with ultra-performance liquid chromatography-ultraviolet
      detection, was proposed for extracting flavonoids from orange fruit peel
      matrices. Molecular sieve SBA-15 was applied for the first time as a solid
      support in trace MSPD. Parameters, such as the type of dispersant, mass ratio of
      the sample to the dispersant, grinding time, and elution pH, were optimized in
      detail. The optimal extraction conditions involved dispersing a powdered fruit
      peel sample (25 mg) into 25mg of SBA-15 and then eluting the target analytes with
      500 MUL of methanol. A satisfactory linearity (r(2) > 0.9990) was obtained, and
      the calculated limits of detection reached 0.02-0.03 MUg/mL for the compounds.
      The results showed that the method developed was successfully applied to
      determine the content of flavonoids in complex fruit peel matrices.

PMID- 26213001
TI  - Molecularly imprinted hydrogels as functional active packaging materials.
AB  - This paper describes the synthesis of novel molecularly imprinted hydrogels
      (MIHs) for the natural antioxidant ferulic acid (FA), and their application as
      packaging materials to prevent lipid oxidation of butter. A library of MIHs was
      synthesized using a synthetic surrogate of FA, 3-(4-hydroxy-3
      methoxyphenyl)propionic acid (HFA), as template molecule, ethyleneglycol
      dimethacrylate (EDMA) as cross-linker, and 1-allylpiperazine (1-ALPP) or 2
      (dimethylamino)ethyl methacrylate (DMAEMA), in combination with 2-hydroxyethyl
      methacrylate (HEMA) as functional monomers, at different molar concentrations.
      The DMAEMA/HEMA-based MIHs showed the greatest FA loading capacity, while the 1
      ALLP/HEMA-based polymers exhibited the highest imprinting effect. During cold
      storage, FA-loaded MIHs protected butter from oxidation and led to TBARs values
      that were approximately half those of butter stored without protection and 25%
      less than those recorded for butter covered with hydrogels without FA,
      potentially extending the shelf life of butter. Active packaging is a new field
      of application for MIHs with great potential in the food industry. 

PMID- 26213000
TI  - In house validation from direct determination of 5-hydroxymethyl-2-furfural (HMF)
      in Brazilian corn and cane syrups samples by HPLC-UV.
AB  - In this work the development and in house validation of the HMF direct
      determination in corn and cane syrups by HPLC-UV was carried out for the first
      time. The separation was done with isocratic elution of a mobile phase comprising
      water (with 0.5% formic acid) and acetonitrile (90:10, v/v) on Phenomenex C18
      column (5.0 MUm, 4.6 * 150 mm), at 30  degrees C, flow rate of 0.8 mL min(-1) and
      detection at 285 nm. The validated method showed excellent performance with low
      limits (LOD and LOQ of 0.09 and 0.26 mg L(-1), respectively), good accuracy
      (recovery rates between 100% and 104%) and precision (RSD's for repeatability and
      intermediate precision between 0.57% and 6.43%). Good selectivity and linearity
      were also observed. HMF contents in both foods were very high (406.6-2121.3 mg
      kg(-1) for corn syrup and 109.2-893.1 mg kg(-1) for cane syrup), which arouses
      concern about food safety of these products.

PMID- 26213002
TI  - Microwave-assisted alkaline extraction of galactan-rich rhamnogalacturonan I from
      potato cell wall by-product.
AB  - Galactan-rich rhamnogalacturonan I (RG I), exhibiting promising health benefits,
      is the most abundant polysaccharide in potato pulp by-product. In the present
      study, the microwave-assisted alkaline extraction of galactan-rich RG I was
      investigated. Solid/liquid ratio was identified as the most significant parameter
      affecting linearly yield and galactose/rhamnose contents. Microwave power and
      solid/liquid ratio exhibited a significant adverse interactive effect on the
      yield. Galactose content of extracted polysaccharides can be modulated by
      compromising between KOH concentration and extraction time, which exhibited
      adverse interaction. Optimum conditions were identified using the established
      predicted models and consisted of treatment of potato cell wall at solid/liquid
      ratio of 2.9% (w/v) with 1.5M KOH under microwave power of 36.0 W for 2.0 min.
      Yield of intact galactan-rich RG I of 21.6% and productivity of 192.0 g/Lh were
      achieved. The functional properties of RG I-rich polysaccharides were comparable
      or superior to potato galactan and oranges homogalacturonan.

PMID- 26213003
TI  - Electrochemical behavior and determination of major phenolic antioxidants in
      selected coffee samples.
AB  - The redox behavior of commercial roasted coffee products were evaluated by
      electroanalysis, whereas high performance liquid chromatography (HPLC) was used
      for determination of cinnamic acid markers, the total phenolic content (TPC) was
      achieved by Folin-Ciocalteu assay, and the traditional DPPH (1-diphenyl-2
      picrylhydrazyl) method for antioxidant power determination. In turn, an optimized
      electrochemical index was proposed to estimate the antioxidant power of different
      samples and it was found a great correlation between all methods. The
      voltammetric profile of all coffee samples was quite similar, presenting the same
      number of peaks at the same potential values. Minor differences on current levels
      were in agreement with the total phenolic and major markers content, as well as,
      to the antioxidant power. Therefore, the electrochemical methods showed to be
      practical, low cost and very useful to evaluate the antioxidant properties of
      coffee samples, which is a relevant quality parameter of this widely consumed
      beverage. 

PMID- 26213004
TI  - Application of nano-encapsulated olive leaf extract in controlling the oxidative
      stability of soybean oil.
AB  - Our objective was to evaluate the antioxidant activity of olive leave extract
      (OLE) encapsulated by nano-emulsions in soybean oil. The average droplet size one
      day after production was 6.16 nm for primary W/O nano-emulsion and, 675 nm and
      1443 nm for multiple emulsions stabilized by WPC alone and complex of WPC-pectin,
      respectively. The antioxidant activity of these emulsions containing three
      concentrations of 100, 200 and 300 mg OLE during storage was evaluated in soybean
      oil by peroxide value, TBA value and rancimat thermal stability test and was
      compared with blank (non-encapsulated) OLE and synthetic TBHQ antioxidant. Nano
      encapsulated OLE was capable of controlling peroxide value better than
      unencapsulated OLE. But because of blocking phenolic compounds within dispersed
      emulsions droplets, thermal stability of encapsulated OLE was lower. To
      summarize, with increased solubility and controlled release of olive leaf
      phenolic compounds through their nano-encapsulation, a higher antioxidant
      activity was achieved.

PMID- 26213005
TI  - Effects of roasting temperature and duration on fatty acid composition, phenolic
      composition, Maillard reaction degree and antioxidant attribute of almond (Prunus
      dulcis) kernel.
AB  - Roasting treatment increased levels of unsaturated fatty acids (linoleic, oleic
      and elaidic acids) as well as saturated fatty acids (palmitic and stearic acids)
      in almond (Prunus dulcis) kernel oils with temperature (150 or 180  degrees C)
      and duration (5, 10 or 20 min). Nonetheless, higher temperature (200  degrees C)
      and longer duration (10 or 20 min) roasting might result in breakdown of fatty
      acids especially for unsaturated fatty acids. Phenolic components (total phenols,
      flavonoids, condensed tannins and phenolic acids) of almond kernels substantially
      lost in the initial phase; afterward these components gradually increased with
      roasting temperature and duration. Similar results also observed for their
      antioxidant activities (scavenging DPPH and ABTS(+) radicals and ferric reducing
      power). The changes of phenolic acid and flavonoid compositions were also
      determined by HPLC. Maillard reaction products (estimated with non-enzymatic
      browning index) also increased with roasting temperature and duration; they might
      also contribute to enhancing the antioxidant attributes.

PMID- 26213006
TI  - Pharmaceuticals in grocery market fish fillets by gas chromatography-mass
      spectrometry.
AB  - Occurrences of pharmaceuticals are evident in aquatic organisms. A reproducible
      gas chromatography-mass spectrometry (GC-MS) method using selected ion monitoring
      (SIM) has been used to determine the anti-histamine diphenhydramine (DPH), anti
      anxiety diazepam (DZP), anti-seizure carbamazepine (CZP) drugs and their
      metabolites in grocery stores fish that were homogenized, extracted, pre
      concentrated, cleaned up, and examined. Identifications of the compounds in
      extracts were obtained by comparing similar mass spectral features and retention
      properties with standards. Among nine frequently detected drugs, only DPH and DZP
      were observed and ranged from 0.61 to 6.21 and 1.99 to 16.57 ng/g, respectively,
      in fourteen fish species. These concentration values were lower than the
      environmental fish. Mean spike recoveries of analytes exceeded 75% with relative
      standard deviations (RSD)<10%. The statistically-derived method detection limits
      (MDLs) for nine compounds ranged from 0.13 to 5.56 ng/g. Average surrogate
      recoveries were 80-85% with 4-9% RSD.

PMID- 26213007
TI  - Pre-harvest application of oxalic acid increases quality and resistance to
      Penicillium expansum in kiwifruit during postharvest storage.
AB  - Kiwifruit (Actinidia deliciosa cv. Bruno) fruits were sprayed with 5mM oxalic
      acid (OA) at 130, 137, and 144 days after full blossom, and then harvested at
      commercial maturity [soluble solid content (SSC) around 10.0%] and stored at room
      temperature (20 +/- 1  degrees C). Pre-harvest application of OA led to fruit
      with higher ascorbic acid content at harvest, slowed the decreases in fruit
      firmness and ascorbic acid content and increase in SSC during storage, and also
      decreased the natural disease incidence, lesion diameter, and patulin
      accumulation in fruit inoculated with Penicillium expansum, indicating that the
      OA treatment increased quality and induced disease resistance in kiwifruit. It
      was suggested that the increase in activities of defense-related enzymes and in
      levels of substances related to disease resistance might collectively contribute
      to resistance in kiwifruit against fungi such as P. expansum in storage.

PMID- 26213008
TI  - Preparation of yolk-shell structured copper oxide@silica oxide spheres and their
      application in high performance electrochemical sensing of Formoterol fumarate
      residues in swine feed and tissues.
AB  - In this paper, we report a facile route to synthesize yolk-shell structured
      copper oxide@silica oxide (CuO@SiO2) spheres and their application to construct
      an electrochemical Formoterol fumarate (FF) sensor. The CuO@SiO2 was
      characterized by means of Fourier transform infrared spectroscopy, X-ray powder
      diffraction, Raman spectroscopy, scanning electron microscopy, and transmission
      electron microscopy. Further, FF was electrocatalytically oxidized at the
      CuO@SiO2 film modified glassy carbon electrode (GCE), which led to a sensitive
      determination of FF. The oxidation current of FF was linear with concentration in
      the range of 0.030-10 MUM and the detection limit was found to be 5.0 nM (S/N =
      3). The observed analytical parameters such as wide linear range, low detection
      limit and short response time were superior to previously reported FF sensors.
      Finally, it was demonstrated that the proposed sensor could be used for the
      selective determination of FF present in swine feed and tissues.

PMID- 26213009
TI  - Tartary buckwheat (Fagopyrum tataricum Gaertn.) starch, a side product in
      functional food production, as a potential source of retrograded starch.
AB  - A starch rich fraction is a side product in Tartary buckwheat processing. This
      study investigated the fractions that are of technological and nutritional
      interest. Tartary buckwheat starch granules had a diameter of 3-14 MUm, and
      presented a typical type "A" X-ray diffraction pattern. They contained nearly
      39.0% amylose. The solubility of Tartary buckwheat starch was much lower at 70-90
      degrees C (ranging within 9.9-10.4% at 90  degrees C) than that in maize (up to
      49.3%) and potato (up to 85.0%) starch. The starch of one variety of Tartary
      buckwheat had significantly lower solubility at 70  degrees C and 80  degrees C
      than that of common buckwheat. The starch peak viscosity and breakdown were
      higher and pasting time was shorter in Tartary buckwheat than in that of the
      starch of common buckwheat. Tartary buckwheat starch had unique pasting and
      physicochemical properties, and is thereby capable of being exploited as a
      suitable raw material of retrograded starch in food processing.

PMID- 26213010
TI  - Assessment of vacuum-dried peppermint (Mentha piperita L.) as a source of natural
      antioxidants.
AB  - The purpose of this study was to investigate the effect of temperature in the
      vacuum drying process of Mentha piperita L. (50 to 90  degrees C). Generally,
      drying processes affect the quality of product, however, vacuum drying works
      under sub-atmospheric pressures. In order to investigate how temperature affects
      this herb, as to color, chlorophyll, total phenolic (TPC), total flavonoid (TFC)
      contents, antioxidant activity by DPPH and ORAC methods. Mineral, vitamin C and
      sugar contents were also evaluated. A slight change in color and chlorophyll
      content was observed in the samples. The highest values for TPC, TFC and
      antioxidant activity methods were obtained at 50 and 70  degrees C however, a
      decrease in the vitamin C content was observed. Minerals such as K, Ca, Mg and Na
      were found. Sucrose showed the highest sugar content. This work suggests that M.
      piperita L. can be used as a natural antioxidant, whether fresh or dried.

PMID- 26213011
TI  - Fatty acids composition of Spanish black (Morus nigra L.) and white (Morus alba
      L.) mulberries.
AB  - This research has determined qualitatively and quantitatively the fatty acids
      composition of white (Morus alba) and black (Morus nigra) fruits grown in Spain,
      in 2013 and 2014. Four clones of each species were studied. Fourteen fatty acids
      were identified and quantified in mulberry fruits. The most abundant fatty acids
      were linoleic (C18:2), palmitic (C16:0), oleic (C18:1), and stearic (C18:0) acids
      in both species. The main fatty acid in all clones was linoleic (C18:2), that
      ranged from 69.66% (MN2) to 78.02% (MA1) of the total fatty acid content;
      consequently Spanish mulberry fruits were found to be rich in linoleic acid,
      which is an essential fatty acid. The fatty acid composition of mulberries
      highlights the nutritional and health benefits of their consumption. 

PMID- 26213012
TI  - Steviol glycosides targeted analysis in leaves of Stevia rebaudiana (Bertoni)
      from plants cultivated under chilling stress conditions.
AB  - Stevia rebaudiana is an important agricultural crop for the production of a high
      potency natural sweetener, sensitive to low temperature during the developmental
      stage. Stimulation of chilling stress with a pre-treatment with endogenous
      signalling components and in particular with salicylic acid (SA), hydrogen
      peroxide (H2O2), 6-benzylaminopurine (BAP) and calcium chloride (CaCl2) could
      induce tolerance to chilling and could constitute a suitable way to maintain
      quality and quantity of steviol glycosides under controlled artificial
      environment. In the present work the effects of different putative signalling
      molecules on the morpho-physiological parameters were evaluated, and a specific
      method for the quali-quantitative analysis of steviol glycosides in S. rebaudiana
      plants cultivated under controlled conditions was developed, by using LC-ESI-FT
      (Orbitrap) MS, LC-ESI-QqQ-MS/MS and multivariate data analysis. This approach
      underlined that the pre-treatment has influence on the production of secondary
      metabolites. In particular Stevia plants characterised by higher contents of
      rebaudioside A and stevioside, were identified. 

PMID- 26213013
TI  - In vitro digestibility and immunoreactivity of bovine milk proteins.
AB  - Current models of digestibility solely utilize pepsin stability to assess the
      safety of allergenic food proteins. However, in vivo complete protein digestion
      requires acid denaturation and pepsin, trypsin, and/or chymotrypsin cleavage.
      This study aimed to identify the immunoreactivity and allergenicity of stable
      bovine milk proteins, using an improved digestibility model to simulate
      physiological gastric and intestinal conditions in vitro. Gel electrophoresis and
      immunoblot analysis were used to determine protein stability and
      immunoreactivity, respectively. Immunoreactivity of bovine milk proteins, beta
      lactoglobulin (beta-LG) and casein (CN) was greatly diminished with gastric
      simulation (0-60 min), but some proteins were stable and immunoreactive with
      simulated intestinal digestive conditions (0-60 min). This study demonstrates the
      need for improved digestibility models for more accurate assessment of the
      behavior of food allergens in vivo.

PMID- 26213014
TI  - Fractionation and reconstitution experiments provide insight into the role of
      wheat starch in frozen dough.
AB  - The wheat dough was subjected to freezing/thawing treatment for 0, 3, 7, and 10
      cycles and fractionated into non-gluten proteins and starch. High-performance
      liquid chromatography revealed changes in molecular mass distribution occurred
      for the extracted non-gluten proteins. As for the residual starch, it reflected a
      loss of chemical components such as amylose, proteins and lipids induced by
      freezing treatment. X-ray diffraction revealed increased crystallinity in
      separated starch as the freezing cycle was repeated. Rapid visco-analyser
      exhibited different pasting behaviors on starch pellets, especially on the
      breakdown and setback viscosities. In the reconstituted dough, an increase was
      observed in storage and loss modulus, corresponding to the presence of
      freezing/thawing-treated starches, which was changed as a result of higher water
      absorption. These results extended the knowledge of starch granules in dough
      deterioration upon freezing process and might contribute to the better
      understanding of frozen dough quality loss. 

PMID- 26213015
TI  - Analysis of hydration parameter for sugars determined from viscosity and its
      relationship with solution parameters.
AB  - The hydration parameter h was obtained from the viscosity B-coefficients and the
      partial molar volume of solute, V2, for various sugars and urea in aqueous
      solutions. The parameter h showed a good correlation with the parameter alpha,
      determined from the activity coefficient of water, representing the solute
      solvent interaction. The parameter h also showed a good correlation with the
      number of equatorial-OH groups (e-OH) for sugars, suggesting that the sugar
      molecules with the higher e-OH fit more to the water-structure. From the
      temperature dependence of the parameter h (dh/dT), the negative dh/dT for sugars
      suggested their water-structure making activity while the positive dh/dT for urea
      corresponded to its structure breaking effect. From the Arrhenius plot, the
      activation energy for h, Ea, was determined to be as low as 10 kJ/mol for
      disaccharides suggesting the stable hydration structure. The Ea increased with a
      decrease in molecular weight for sugars.

PMID- 26213016
TI  - Effect of tartarate and citrate based food additives on the micellar properties
      of sodium dodecylsulfate for prospective use as food emulsifier.
AB  - Citrate and tartarate based food preservatives can be used to enhance the
      emulsifying properties of sodium dodecylsulfate (SDS) based micellar system and
      thus making it appropriate for food applications. Exploration of interactions
      between the two species is the key constraint for execution of such ideas. In
      this work various micellar and thermodynamic parameters of SDS like critical
      micellar concentration (CMC), standard Gibbs free energy of micellization
      (DeltaG(0)mic.) etc. have been calculated in different concentrations of disodium
      tartarate (DST) and trisodium citrate (TSC) in the temperature range (288.15
      318.15)K from the conductivity and surface tension measurements. The parameters
      obtained from these studies reveal the competitive nature of both the additives
      with SDS for available positions at the air/water interface. TSC is found to be
      more effective additive in order to make SDS micellar system better for its
      potential applications as food emulsifier. 

PMID- 26213017
TI  - An efficient continuous flow process for the synthesis of a non-conventional
      mixture of fructooligosaccharides.
AB  - A sustainable and scalable process for the production of a new mixture of
      fructooligosaccharides (FOS) was developed using a continuous-flow approach based
      on an immobilized whole cells-packed bed reactor. The technological transfer from
      a classical batch system to an innovative flow environment allowed a significant
      improvement of the productivity. Moreover, the stability of this production
      system was ascertained by up to 7 days of continuous working. These results
      suggest the suitability of the proposed method for a large-scale production of
      the desired FOS mixture, in view of a foreseeable use as a novel prebiotic
      preparation.

PMID- 26213018
TI  - Microencapsulation and storage stability of polyphenols from Vitis vinifera grape
      wastes.
AB  - Wine production wastes are an interesting source of natural polyphenols. In this
      work, wine wastes extracts were encapsulated through vibration nozzle
      microencapsulation using sodium alginate as polymer and calcium chloride as
      hardening reagent. An experimental design approach was used to obtain calcium
      alginate microbeads with high polyphenol content and good morphological features.
      In this way, the effect of pressure, frequency, voltage and the distance to the
      gelling bath were optimized for two nozzles of 150 and 300 MUm. Long-term
      stability of the microbeads was studied for 6 months taking into account
      different storage conditions: temperatures (4  degrees C and room temperature),
      in darkness and in presence of light, and the addition of chitosan to the gelling
      bath. Encapsulated polyphenols were found to be much more stable compared to free
      polyphenols regardless the encapsulation procedure and storage conditions.
      Moreover, slightly lower degradation rates were obtained when chitosan was added
      to the gelling bath.

PMID- 26213019
TI  - Industrial scale microwave processing of tomato juice using a novel continuous
      microwave system.
AB  - This study evaluated the effect of an industrial scale continuous flow microwave
      volumetric heating system in comparison to conventional commercial scale
      pasteurisation for the processing of tomato juice in terms of physicochemical
      properties, microbial characteristics and antioxidant capacity. The effect
      against oxidative stress in Caco-2 cells, after in vitro digestion was also
      investigated. Physicochemical and colour characteristics of juices were very
      similar between technologies and during storage. Both conventional and microwave
      pasteurisation inactivated microorganisms and kept them in low levels throughout
      storage. ABTS[Symbol: see text](+) values, but not ORAC, were higher for the
      microwave pasteurised juice at day 0 however no significant differences between
      juices were observed during storage. Juice processed with the microwave system
      showed an increased cytoprotective effect against H2O2 induced oxidation in Caco
      2 cells. Organoleptic analysis revealed that the two tomato juices were very
      similar. The continuous microwave volumetric heating system appears to be a
      viable alternative to conventional pasteurisation.

PMID- 26213020
TI  - High-yield synthesis of bioactive ethyl cinnamate by enzymatic esterification of
      cinnamic acid.
AB  - In this paper, Lipozyme TLIM-catalyzed synthesis of ethyl cinnamate through
      esterification of cinnamic acid with ethanol was studied. In order to increase
      the yield of ethyl cinnamate, several media, including acetone, isooctane, DMSO
      and solvent-free medium, were investigated in this reaction. The reaction showed
      a high yield by using isooctane as reaction medium, which was found to be much
      higher than the yields reported previously. Furthermore, several parameters such
      as shaking rate, water activity, reaction temperature, substrate molar ratio and
      enzyme loading had important influences on this reaction. For instance, when
      temperature increased from 10 to 50  degrees C, the initial reaction rate
      increased by 18 times and the yield of ethyl cinnamate increased by 6.2 times.
      Under the optimum conditions, lipase-catalyzed synthesis of ethyl cinnamate gave
      a maximum yield of 99%, which was of general interest for developing industrial
      processes for the preparation of ethyl cinnamate.

PMID- 26213021
TI  - Modelling stochastic variability and uncertainty in aroma active compounds of PEF
      treated peach nectar as a function of physical and sensory properties, and
      treatment time.
AB  - Effects of pulsed electric field (PEF) processing on 28 aroma active compounds,
      and four physical and eight sensory properties of peach nectar were explored
      using the best-fit multiple linear regression (MLR) models and Monte Carlo
      simulations as a function of the treatment times of 0, 66, 131, and 210 MUs. The
      PEF treatment time of 131 MUs on average led consistently to the least loss of
      most compounds. Significantly enhanced or no significant changes in the sensory
      properties were found as a function of the PEF treatment times. The most
      influential sensory predictor of the 28 MLR models was flavour, while the aroma
      compound most influential on the sensory properties of aftertaste, flavour,
      sweetness, and overall acceptance was octadecanoic acid. Monte Carlo simulations
      were used for the probabilistic assessments of stochastic variability and
      uncertainty associated with aroma active compounds of PEF-treated peach nectar.

PMID- 26213022
TI  - HS-GC-MS volatile compounds recovered in freshly pressed 'Wonderful' cultivar and
      commercial pomegranate juices.
AB  - Consumption and production of superfruits has been increasing. Highly colored
      fruits often have bitter and astringent components that may make them
      undesirable, especially when processed. Many pomegranate volatile reports
      involved commercial samples, complicated isolation methods, or blending and
      concentrating that were from arils only, cultivars other than 'Wonderful', or
      mixed cultivars. Solid phase microextraction (SPME), polydimethylsiloxane stir
      bar sorptive extraction, and Tenax adsorption were performed with freshly pressed
      'Wonderful' juices, commercial juices and concentrates. Using SPME, 36 compounds
      were isolated in whole pressed 'Wonderful' juices, including 18 of the 21
      consensus compounds. In arils-only juices, 41 compounds were isolated by SPME,
      including 17 of the consensus volatiles. Dramatic variation existed in volatiles
      recovered in commercial juices and isolation of consensus compounds was sporadic.
      This article and summary of the literature serves to possibly deliver an improved
      volatile data set via a rapid method for fresh and partially processed (pressed)
      pomegranates. 

PMID- 26213023
TI  - Determination of sulfur and nitrogen compounds during the processing of dry
      fermented sausages and their relation to amino acid generation.
AB  - The identification of odor-active sulfur and nitrogen compounds formed during the
      processing of dry fermented sausages was the objective of this study. In order to
      elucidate their possible origin, free amino acids (FAAs) were also determined.
      The volatile compounds present in the dry sausages were extracted using solvent
      assisted flavor evaporation (SAFE) and monitored by one and two-dimensional gas
      chromatography with different detectors: mass spectrometry (MS), nitrogen
      phosphorous (NPD), flame photometric (FPD) detectors, as well as gas
      chromatography-olfactometry. A total of seventeen sulfur and nitrogen compounds
      were identified and quantified. Among them, 2-acetyl-1-pyrroline was the most
      potent odor active compound, followed by methional, ethylpyrazine and 2,3
      dihydrothiophene characterized by toasted, cooked potato, and nutty notes. The
      degradation of FAAs, generated during processing, was related to the production
      of aroma compounds, such as methionine forming methional and benzothiazole while
      ornithine was the precursor compound for 2-acetyl-1-pyrroline and glycine for
      ethylpyrazine. 

PMID- 26213024
TI  - Gas phase plasma impact on phenolic compounds in pomegranate juice.
AB  - The aim of the study was to evaluate the effect of gas phase plasma on phenolic
      compounds in pomegranate juice. The potential of near infrared reflectance
      spectroscopy combined with partial least squares for monitoring the stability of
      phenolic compounds during plasma treatment was explored, too. Experiments are
      designed to investigate the effect of plasma operating conditions (treatment time
      3, 5, 7 min; sample volume 3, 4, 5 cm(3); gas flow 0.75, 1, 1.25 dm(3) min(-1))
      on phenolic compounds and compared to pasteurized and untreated pomegranate
      juice. Pasteurization and plasma treatment resulted in total phenolic content
      increasing by 29.55% and 33.03%, respectively. Principal component analysis and
      sensitivity analysis outputted the optimal treatment design with plasma that
      could match the pasteurized sample concerning the phenolic stability (5 min/4
      cm(3)/0.75 dm(3) min(-1)). Obtained results demonstrate the potential of near
      infrared reflectance spectroscopy that can be successfully used to evaluate the
      quality of pomegranate juice upon plasma treatment considering the phenolic
      compounds.

PMID- 26213025
TI  - Phytochemistry, antioxidant capacity, total phenolic content and anti
      inflammatory activity of Hibiscus sabdariffa leaves.
AB  - A liquid chromatography-mass spectrometry method was developed for the
      simultaneous separation, and determination of natural compounds including
      phenolic acids and flavonoids in the leaves of Hibiscus sabdariffa. By analyzing
      the UV and MS data, and comparison with authenticated standards, 10 polyphenols
      including neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid,
      quercetin, kaempferol and their glycosides were identified together with 5
      (hydroxymethyl)furfural. Major constituents in the leaves of 25 different
      populations from worldwide accessions were quantified and compared with each
      other. The total phenolic content of each accession was determined using Folin
      Ciocalteu assay, ranging from 18.98 +/- 2.7 to 29.9 +/- 0.5 mg GAE/g. Their in
      vitro antioxidant activities were measured by ABTS radical cation decolorization
      assay, varying from 17.5 to 152.5 +/- 18.8 MUmol Trolox/g. After the treatment of
      H. sabdariffa leaf extract, the reduction of LPS-induced NO production dose
      dependently in RAW 264.7 cell indicates the extract's potential anti-inflammatory
      activity.

PMID- 26213026
TI  - Transepithelial transport of milk derived bioactive peptide VLPVPQK.
AB  - The transepithelial transport of an antioxidative and ACE inhibitory peptide,
      VLPVPQK (named peptide C) derived from casein hydrolysates was investigated along
      with extensively studied opioid peptide beta-casomorphin using a human intestinal
      cell (Caco-2) monolayer. The susceptibility to the brush-border peptidases and
      route of transepithelial transport were observed to be the primary factors
      influencing the transport of these peptides. The apical to basal transport
      mechanism was studied using bradykinin as control as it shows resistance to
      cellular peptidases and its route of transepithelial transport had been
      established. VLPVPQK and BCM 5 were hydrolyzed by cellular peptidases while
      bradykinin was found intact. The transport of VLPVPQK (1.0%) was found to be
      relatively much higher than BCM 5 (0.03%) and bradykinin (0.1%). Interestingly
      the effect of some inhibitors on the transport of VLPVPQK suggested involvement
      of PepT1 like transporters/SOPT2 while BCM 5, its hydrolytic product and
      bradykinin were suggested to be transported mainly via the intracellular
      transcytosis pathway. 

PMID- 26213027
TI  - Quantification of prominent volatile compounds responsible for muskmelon and
      watermelon aroma by purge and trap extraction followed by gas chromatography-mass
      spectrometry determination.
AB  - A dynamic headspace purge-and-trap (DHS-P&T) methodology for the determination
      and quantification of 61 volatile compounds responsible for muskmelon and
      watermelon aroma has been developed and validated. The methodology is based on
      the application of purge-and-trap extraction followed by gas chromatography
      coupled to (ion trap) mass spectrometry detection. For this purpose two different
      P&T sorbent cartridges have been evaluated. The influence of different extraction
      factors (sample weight, extraction time, and purge flow) on extraction efficiency
      has been studied and optimised using response surface methodology. Precision,
      expressed as repeatability, has been evaluated by analysing six replicates of
      real samples, showing relative standard deviations between 3% and 27%. Linearity
      has been studied in the range of 10-6130 ng mL(-1) depending on the compound
      response, showing coefficients of correlation between 0.995 and 0.999. Detection
      limits ranged between 0.1 and 274 ng g(-1). The methodology developed is well
      suited for analysis of large numbers of muskmelon and watermelon samples in plant
      breeding programs.

PMID- 26213028
TI  - Rapid detection of volatile compounds in apple wines using FT-NIR spectroscopy.
AB  - The purpose of this work was to study the possibility and ability of NIR
      spectroscopy to determine the volatile compounds in apple wines. To achieve this,
      seventy-two samples were scanned using NIR transmission spectroscopy. The
      volatile compounds were analyzed using HS-SPME-GC-MS. Partial least square (PLS)
      regression with full cross-validation was applied to develop the calibration
      models. The calibration results using 42 apple wine samples had a coefficient of
      determination in full cross validation (Rcv(2)) between 0.8916 for hexanol and
      0.8278 for 3,4,5-trimethyl-4-heptanol. The predictive ability of the models was
      further confirmed by external validation procedure with an independent sample set
      which did not belong to the calibration group. The resulting values of Rp(2)
      ranged from 0.9184 for ethyl hexanoate to 0.8811 for 2-phenethanol and 3,4,5
      trimethyl-4-heptanol. The residual predictive deviation (RPD) obtained was higher
      than 2.9 in all the compounds. The results demonstrate that near infrared
      spectroscopy can be used as a rapid tool to determine the volatile compounds in
      apple wines. 

PMID- 26213029
TI  - Inhibitory effect of synthetic aromatic heterocycle thiosemicarbazone derivatives
      on mushroom tyrosinase: Insights from fluorescence, (1)H NMR titration and
      molecular docking studies.
AB  - Three structurally similar aromatic heterocyclic compounds 2
      thiophenecarboxaldehyde (a), 2-furaldehyde (b), 2-pyrrolecarboxaldehyde (c) were
      chosen and a series of their thiosemicarbazone derivatives(1a-3a, 1b-3b and 1c
      3c) were synthesized to evaluate their biological activities as mushroom
      tyrosinase inhibitors. The inhibitory effects of these compounds on tyrosinase
      were investigated by using spectrofluorimetry, (1)H NMR titration and molecular
      docking techniques. From the results of fluorescence spectrum and (1)H NMR
      titration, it was found that forming complexes between the sulfur atom from
      thiourea and copper ion of enzyme center may play a key role for inhibition
      activity. Moreover, investigation of (1)H NMR spectra further revealed that
      formation of hydrogen bond between inhibitor and enzyme may be helpful to above
      complexes formation. The results were well coincident with the suggestion of
      molecular docking and obviously showed that 2-thiophone N(4)-thiosemicarbazone
      (1a), 2-furfuran N(4)-thiosemicarbazone (1b) and 2-pyrrole N(4)-thiosemicarbazone
      (1c) are potential inhibitors which deserves further investigation. 

PMID- 26213030
TI  - The behaviour of whey protein isolate in protecting Lactobacillus plantarum.
AB  - There is increasing evidence that whey protein isolates (WPI), can be utilised to
      encapsulate and protect bioactive substances, including lactic acid bacteria, due
      to their physicochemical properties. However, little is known about what happens
      in the immediate vicinity of the cells. This study examined the protective
      behaviour of WPI for two strains of Lactobacillus plantarum, A17 and B21, during
      spray drying. B21 was found to be more hydrophobic than A17 and required 50% of
      the amount of WPI to provide comparably high survival (~ 90%). We hypothesise
      that WPI protects the hydrophobic bacteria by initial attachment to the unfolded
      whey protein due to hydrophobic interactions followed by adhesion to the
      proteins, resulting in cells being embedded within the walls of the capsules. The
      encapsulated strains had a moisture content of approximately 5.5% and during
      storage trials at 20  degrees C retained viability for at least eight weeks.

PMID- 26213031
TI  - Antioxidant and antimicrobial activities of commercial rice wine extracts of
      Taiwanese Allium fistulosum.
AB  - The antioxidant and antibacterial activities of commercial rice wine extracts
      obtained from different plant parts of Allium fistulosum were assayed. The
      results showed that commercial rice wine extracts of A. fistulosum contained 28.3
      95.9 MUL/mL allicin and exhibited significant antioxidant and antibacterial
      activities. The DPPH radical scavenging capacity ranged from 90.2% to 52.1%, and
      the IC50 value ranged from 14.6 to 26.0 MUg/mL. The total phenolic content of
      wine extracts was 56.4-198.9 mg GAE/g extracts. The TEAC assay of extracts ranged
      from 6.2 to 15.5 mmol/g extracts. Antibacterial activities were tested against 4
      bacteria b y using agar disc diffusion and tube dilution tests. All extracts
      exhibited antibacterial activities against gram-positive bacteria, such as
      Bacillus subtilis and Staphylococcus aureus, and gram-negative bacteria, such as
      Escherichia coli and Pseudomonas aeruginosa. Thus, A. fistulosum wine extracts
      could be used as natural and functional additives in cooking foods.

PMID- 26213032
TI  - The impact of red cabbage fermentation on bioavailability of anthocyanins and
      antioxidant capacity of human plasma.
AB  - The effect of red cabbage fermentation on anthocyanin bioavailability and plasma
      antioxidant capacity in humans was studied. In a randomized crossover study, 13
      volunteers consumed fresh and fermented red cabbage. Blood and urine samples were
      collected before and after consumption. Analyses of anthocyanins by HPLC-MS/MS
      and plasma antioxidant capacity by photochemiluminescence assay were conducted.
      Red cabbage products contained 20 different nonacylated and acylated anthocyanins
      with the main structure of cyanidin triglucosides. The anthocyanins ingested were
      present in physiological fluids in form of 18 native anthocyanins and 12
      metabolites (methylated, glucuronided, sulfated). Among cyanidin metabolites
      identified, methylated forms were predominant. Bioavailability of anthocyanin
      from fresh red cabbage was over 10% higher than from fermented red cabbage. Upon
      fresh cabbage consumption, volunteers plasma showed higher antioxidant capacity
      than after fermented cabbage intake. The study has shown that fermentation
      process affects red cabbage anthocyanins bioavailability and human plasma
      antioxidant capacity. 

PMID- 26213033
TI  - Two-year comparison of the biochemical properties of polyphenol oxidase from
      Turkish Alyanak apricot (Prunus armenica L.).
AB  - Polyphenol oxidase (PPO) was extracted and purified from Turkish Alyanak apricot
      variety and its characteristics were studied in two consecutive years (2008 and
      2009). Three isoenzymes (isoenzyme A1, A2 and B) were obtained upon ammonium
      sulfate fractionation, ion exchange chromatography using DEAE-Toyopearl 650 M and
      gel filtration chromatography using Sephadex G-100. The isoenzymes exhibited
      different kinetic properties. Furthermore, year-to-year variability in Km and
      Vmax values was significant. The pH optimum for enzyme activity was 4.98 for
      isoenzymes A1 and A2, and 5.8 for isoenzyme B. The isoenzymes A1 and B had
      optimum temperature at 30  degrees C in both years whereas isoenzyme A2 had
      maximum activity at 40  degrees C in 2008 and 30  degrees C in 2009. The
      inactivation kinetics parameters and the effects of inhibitors tested exhibited
      significant year-to-year variation.

PMID- 26213034
TI  - Oxidation kinetics of common Kilka (Clupeonella cultiventris caspia) oil in
      presence of bene oils' unsaponifiable matter.
AB  - The oxidation mechanisms and kinetics of the purified common Kilka (Clupeonella
      cultiventris caspia) triacylglycerols (PKO) as affected by 1-1.5% (w/w) of
      unsaponifiable matters of bene kernel (UKO) and hull (UHO) oils were studied and
      compared with that of 100 mg/kg of butylated hydroxytoluene (BHT) and alpha
      tocopherol in the Rancimat test at 50-70  degrees C. There were good correlations
      between the oxidative stability index (OSI) and time required to reach a 50%
      increase in PV (t50). The frequency factor (A) and activation energy (Ea) were
      correlated well with the values of entropy and enthalpy, respectively. The values
      of free energy of activation (DeltaG(++)) could describe the values of t50 or OSI
      well. Kinetic data indicated that the UKO with higher contents of tocopherols and
      tocotrienols, and terpenoid compounds was more effective than the UHO on the PKO
      stability.

PMID- 26213035
TI  - Influence of fermentation on glucosinolates and glucobrassicin degradation
      products in sauerkraut.
AB  - A systematic investigation was carried out on the influence of fermentation on
      glucosinolates and their degradation products from fresh raw cabbage, throughout
      fermentation at 20  degrees C and storage at 4  degrees C. Glucosinolates were
      degraded dramatically between Day 2 and 5 of fermentation and by Day 7 there was
      no detectable amount of glucosinolates left. Fermentation led to formation of
      potential bioactive compounds ascorbigen (13.0 MUmol/100 g FW) and indole-3
      carbinol (4.52 MUmol/100g FW) with their higher concentrations from Day 5 to Day
      9. However, during storage indole-3-carbinol slowly degraded to 0.68 MUmol/100 g
      FW, while ascorbigen was relatively stable from Week 4 until Week 8 at 6.78
      MUmol/100 g FW. In contrast, the content of indole-3-acetonitrile decreased
      rapidly during fermentation from 3.6 to 0.14 MUmol/100 g FW. The results imply a
      maximum of health beneficial compounds after fermentation (7-9 days) in contrast
      to raw cabbage or stored sauerkraut.

PMID- 26213036
TI  - Functional analysis of differentially expressed proteins in Chinese bayberry
      (Myrica rubra Sieb. et Zucc.) fruits during ripening.
AB  - This study developed a proteome reference map of Myrica rubra fruits at the
      green, pink and red stages during ripening using two-dimensional gel
      electrophoresis (2-DE). Forty-six differentially expressed proteins were detected
      in the gel, of which 43 were successfully identified by matrix-assisted laser
      desorption ionization time-of-flight/time-of-flight mass spectrometry and protein
      database searching. We found that malic enzyme related to the decrease of organic
      acid acidity was up-regulated. The high abundance of pyruvate decarboxylase and
      alcohol dehydrogenase may contribute to fruit peculiar fragrant characteristics.
      Phenylalanine ammonia-lyase, chalcone synthase 11, UDP-glucose:flavonoid 3-O
      glucosyltransferase, and anthocyanidin synthase, enzymes involved in the
      anthocyanin metabolic pathway, were all up-regulated. The physiological data
      agree with fruit proteome results. These findings provided insights into the
      metabolic processes and regulatory mechanisms during Chinese bayberry fruit
      ripening. 

PMID- 26213037
TI  - Antioxidant and antiproliferative activities in different maturation stages of
      broccoli (Brassica oleracea Italica) biofortified with selenium.
AB  - In this work, three different broccoli maturity stages subjected to
      biofortification with selenium were evaluated for antioxidant and
      antiproliferative activities. Antioxidant trials have shown that the maturation
      stages biofortified with selenium had significantly higher amounts of phenolic
      compounds and antioxidant activity, especially seedlings. Although non-polar
      extracts of all samples show antiproliferative activity, the extract of broccoli
      seedlings biofortified with selenium stood out, presenting cytocidal activity for
      a glioma line (U251, GI50 28.5 mg L(-1)).

PMID- 26213039
TI  - Flesh quality and biochemistry of light-manipulated Atlantic cod (Gadus morhua)
      and the significance of collagen cross-links on fillet firmness and gaping.
AB  - The aim of our study was to investigate whether light-manipulation, causing
      accelerated or delayed maturation, could be used as a tool to improve fillet
      gaping score and texture of farmed cod (Gadus morhua L.) harvested during summer.
      Control and accelerated groups had completed spawning by the time of harvest, and
      expressed sexual dimorphism in various biometric and flesh quality parameters.
      Pyridinoline cross-links, a key biochemical parameter investigated, were
      positively correlated with texture (r(2) = 0.4), as also were cathepsin B&L and
      sex. Gaping was also impacted by pyridinoline cross-links, together with body
      mass and maturation. Interestingly, the level of gaping was significantly reduced
      with a pyridinoline cross-link concentration of >2500 pmols g(-1) dry mass. In
      conclusion, light-manipulation can be used as a tool to improve flesh texture of
      farmed cod with a low gaping score, but with compromise of increased dress out
      percentage for the accelerated group.

PMID- 26213038
TI  - Conservation of (87)Sr/(86)Sr isotopic ratios during the winemaking processes of
      'Red' wines to validate their use as geographic tracer.
AB  - (87)Sr/(86)Sr has been determined in wines, musts grape juices, soils and rocks
      from six selected vineyards of 'Cesanese' wine area. Cesanese is a monocultivar
      wine from a small region characterised by different geologic substrata, a key
      locality to test the influence of both substratum and winemaking procedure on the
      (87)Sr/(86)Sr of wines. Experimental work has been performed on wines from
      different vintage years to check possible seasonal variations. The data reveal
      that (87)Sr/(86)Sr does not change through time, to validate the selection of
      wineries performed, and in addition no isotopic variations are observed during
      winemaking. Indeed, no significant isotopic variations have been observed in
      musts and wines. These findings reinforce the hypothesis that the isotopic
      signature of wines is strongly related to the bioavailable fraction of the soil
      rather than to its bulk. The data corroborate the possibility that Sr-isotopes of
      high-quality wines can be used as a reliable tool for fingerprinting wine
      geographic provenance. 

PMID- 26213040
TI  - Method validation and dissipation kinetics of four herbicides in maize and soil
      using QuEChERS sample preparation and liquid chromatography tandem mass
      spectrometry.
AB  - A versatile liquid chromatography tandem mass spectrometry method with modified
      QuEChERS (quick, easy, cheap, effective, rugged, and safe) sample preparation was
      developed for the determination of rimsulfuron, mesotrione, fluroxypyr-meptyl,
      and fluroxypyr. By adjusting the amount of graphitized carbon black, the
      herbicide analytes could be quantified with satisfactory recoveries in the range
      of 80-110%. A dissipation kinetics study conducted under open field conditions at
      two sites during 2014 showed first order equations with half-lives between 0.6d
      and 3.6d, illustrating an appropriate degree of stability and safety. The
      dissipation kinetics were different in the different matrices. Although the
      herbicides had higher initial residues in straw than those in soil, they degraded
      faster in straw. The terminal residues for the herbicides formulated in two water
      dispersible granules were all below maximum residue limits. These results not
      only gave insights about the analytes but also contributed to environmental
      protection and food safety. 

PMID- 26213041
TI  - Production of natural melanin by Auricularia auricula and study on its molecular
      structure.
AB  - In this study, the production and structure of melanin produced by Auricularia
      auricula have been determined and analyzed in detail. The results showed that the
      highest mycelial growth rate was observed in low-carbon and carbon-free medium.
      In low-nitrogen and nitrogen-free medium, melanin yield was very low. Deficiency
      of tyrosine in medium led to weak secretion of melanin. The inorganic salt could
      markedly influence mycelia morphology, but did not obviously impact mycelia
      growth rate and melanin yield. Meanwhile the condensed molecular formula
      ([C18(OR)3H7O4N2]n) and structural formula of melanin were concluded based on UV
      Vis, HPLC, FTIR, NMR and elemental assay. This is an eumelanin and also a
      macromolecular polymer of 5,6-dihydroxyindole and 5,6-dihydroxyindole-2
      carboxylic acid. The 6 main components were phenolic hydroxyl, carboxyl,
      amidogen, carbonyl, methylene, methyne and sulfur. This work testified that
      nutritional control was very important to promote melanin production, making
      melanin more affordable as material in food, cosmetics and medicines. 

PMID- 26213042
TI  - Stability of anthocyanins- and anthocyanidins-enriched extracts, and formulations
      of fruit pulp of Eugenia jambolana ('jamun').
AB  - The fruit pulp of Eugenia jambolana (jamun) is a rich source of anthocyanins
      (ACs). The purpose of the present study was to assess the effect of various
      physical and chemical factors on the stability of ACs and anthocyanidins (ACdn)
      in the crude, anthocyanins-enriched extract (ACs-EEX), anthocyanins-enriched
      sephadex extract (ACs-EES) and anthocyanidins-enriched extract (ACdn-EEX). ACs
      and ACdn contents were analyzed using a stability indicating HPLC analytical
      method. The ACs content reduced to 86.4% (crude extract), 60.9% (ACs-EEX), 36.0%
      (ACs-EES), 64.8% (ACs-EEX tablet), and 71.7% (ACs-EEX capsules) after 1 year at 5
      degrees C. The ACdn content reduced to 83.1% (ACdn-EEX), 90.1% (ACdn-EEX tablet)
      and 93.8% (ACdn-EEX capsules) after 1 year at 5  degrees C. ACs and ACdn showed
      lesser degradation at low pH and higher degradation at high H2O2 concentration.
      The thermal degradation products of ACs were identified and quantified.

PMID- 26213043
TI  - Dual enzymatic biosensor for simultaneous amperometric determination of histamine
      and putrescine.
AB  - A disposable electrodic system consisting of two working electrodes connected in
      array mode has been developed for the simultaneous determination of histamine
      (His) and putrescine (Put). Histamine deshydrogenase and putrescine oxidase
      enzymes were respectively immobilized by crosslinking on each working screen
      printed electrode, both modified with tetrathiafulvalene. The dual system allowed
      the simultaneous amperometric determination of both species by measuring the
      oxidation current of the mediator in each working electrode. The effect of other
      potentially interfering biogenic amines was also evaluated. The capability of
      detection was of 8.1 +/- 0.7 for His and 10 +/- 0.6 MUM for Put. The precision in
      terms of relative standard deviation was of 3.5% and 6.7% for His and Put,
      respectively. The developed biosensor was successfully applied to the
      determination of His and Put in different food samples.

PMID- 26213044
TI  - Inhibitory effect of pomegranate (Punica granatum L.) polyphenol extracts on the
      bacterial growth and survival of clinical isolates of pathogenic Staphylococcus
      aureus and Escherichia coli.
AB  - In the present study major polyphenols of pomegranate arils and peel by-products
      were extracted in 50% (v/v) aqueous ethanol, characterized and used in
      microbiological assays in order to test antimicrobial activity against clinically
      isolated human pathogenic microorganisms. Total concentration of polyphenols and
      in vitro antioxidant properties were determined by the Folin-Ciocalteu and DPPH
      methods, respectively. The most abundant bioactive molecules, including
      anthocyanins, catechins, tannins, gallic and ellagic acids were identified by RP
      HPLC-DAD, also coupled to off-line matrix assisted laser desorption/ionization
      (MALDI-TOF) mass spectrometry (MS). The inhibitory spectrum of extracts against
      test microorganisms was assessed by the agar well-diffusion method. Data herein
      indicated that both pomegranate aril and peel extracts have an effective
      antimicrobial activity, as evidenced by the inhibitory effect on the bacterial
      growth of two important human pathogens, including Staphylococcus aureus and
      Escherichia coli, which are often involved in foodborne illness. 

PMID- 26213045
TI  - Chlorogenic acid increased 5-hydroxymethylfurfural formation when heating
      fructose alone or with aspartic acid at two pH levels.
AB  - Chlorogenic acid (CGA) is a phenolic acid that ubiquitously exists in fruits.
      This work aims to investigate whether and how CGA influences HMF formation during
      heating fructose alone, or with an amino acid. The results showed that that CGA
      increased 5-hydroxymethylfurfural (HMF) formation. At pH 5.5 and 7.0, the
      addition of 5.0 MUmol/ml CGA increased HMF formation by 49.4% and 25.2%,
      respectively when heating fructose alone, and by 9.0% and 16.7%, respectively
      when heating fructose with aspartic acid. CGA significantly increased HMF
      formation by promoting 3-deoxosone formation, and its conversion to HMF by
      inhibiting HMF elimination, especially in the Maillard reaction system. A
      comparison of the catalytic capacity of CGA with its six analogous compounds
      showed that both its di-hydroxyphenyl and carboxyl groups function in increasing
      HMF formation.

PMID- 26213046
TI  - Influence of succinylation on physicochemical property of yak casein micelles.
AB  - Succinylation is a chemical-modification method that affects the physicochemical
      characteristics and functional properties of proteins. This study assessed the
      influence of succinylation on the physicochemical properties of yak casein
      micelles. The results revealed that surface hydrophobicity indices decreased with
      succinylation. Additionally, denaturation temperature and denaturation enthalpy
      decreased with increasing succinylation level, except at 82%. The buffering
      properties of yak casein micelles were affected by succinylation. It was found
      that chemical modification contributed to a slight shift of the buffering peak
      towards a lower pH value and a markedly increase of the maximum buffering values
      of yak casein micelles at pH 4.5-6.0 and pH < 3. Succinylation increased yak
      casein micellar hydration and whiteness values. The findings obtained from this
      study will provide the basic information on the physicochemical properties of
      native and succinylated yak casein micelles.

PMID- 26213047
TI  - Rapid and quantitative detection of 4(5)-methylimidazole in caramel colours: A
      novel fluorescent-based immunochromatographic assay.
AB  - A novel fluorescence-based immunochromatographic assay (ICA) for rapid detecting
      4(5)-methylimidazole (4-MI) is presented in this study. In our work, the
      conjugates of fluorescent microspheres (FMs) and 4-MI monoclonal antibody were
      used as probe for ICA. Under optimal conditions, a standard curve of ICA-based
      detection of 4-MI was developed, linear detection ranged from 0.50 to 32.0 mg/L.
      The cross-reactivities were observed less than 3.93% by detecting 6 selected
      structural analogues of 4-MI. The recoveries of 4-MI in caramels detection were
      ranged from 82.85% to 102.31%, with the coefficient of variation (n = 3) below
      9.06%. Quantitative comparison of the established fluorescence-based ICA with
      high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and
      indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) analysis of
      real caramel colour samples indicated a good correlation among the methods.
      Therefore, our developed fluorescence-based ICA method shows great potential for
      simple, rapid, sensitive, and cost-effective quantitative detection of 4-MI in
      food safety control.

PMID- 26213048
TI  - Physicochemical characterization of pomegranate wines fermented with three
      different Saccharomyces cerevisiae yeast strains.
AB  - Three commercial Saccharomyces cerevisiae yeast strains: Viniferm Revelacion,
      Viniferm SV and Viniferm PDM were evaluated for the production of pomegranate
      wine from a juice coupage of the two well-known varieties Mollar and Wonderfull.
      Further malolactic fermentation was carried out spontaneously. The same
      fermentation patterns were observed for pH, titratable acidity, density, sugar
      consumption, and ethanol and glycerol production. Glucose was exhausted while
      fructose residues remained at the end of alcoholic fermentation. A high ethanol
      concentration (10.91 +/- 0.27% v/v) in combination with 1.49 g/L glycerol was
      achieved. Citric acid concentration increased rapidly a 31.7%, malic acid
      disappeared as result of malolactic fermentation and the lactic acid levels
      reached values between 0.40 and 0.96 g/L. The analysis of CIEa parameter and
      total anthocyanin content highlights a lower degradation of monomeric
      anthocyanins during winemaking with Viniferm PDM yeast. The resulting wine
      retains a 34.5% of total anthocyanin content of pomegranate juice blend.

PMID- 26213049
TI  - Effect of selective breeding on collagen properties of Atlantic salmon (Salmo
      salar L.).
AB  - Collagen content and properties of skeletal muscle were studied among selected
      (FP) and unselected (WP) Atlantic salmon lines that were reared together to avoid
      any environmental effects. The FP group had significantly higher body weight at
      harvesting, softer texture and lower connective tissue yield compared with the WP
      group. The relative collagen fractions (acid, pepsin, insoluble) were similar,
      but the FP group had a greater abundance of amino acids involved in collagen
      triple helix conformation and stabilisation (Gly, Pro, Hyp and Hyl), whilst the
      Lys content was greater for the WP group, indicating a more aggregated collagen.
      The connective tissue denaturation temperature was lower for the FP group,
      coinciding with a lower degree of collagen self-assembly and intermolecular
      crosslinks. It is concluded that selective breeding has resulted in lower
      connective tissue stability of Atlantic salmon fillets. 

PMID- 26213050
TI  - Multi-response optimization of factors affecting ultrasonic assisted extraction
      from Iranian basil using central composite design.
AB  - The present study reports on the extraction of antioxidant compounds from Iranian
      Ocimum basilicum. Central composite design (CCD) was used to investigate the
      effect of extraction variables on the ultrasound-assisted extraction (UAE). Three
      independent variables including temperature, methanol to water ratio percent, and
      sonication time were studied for simultaneous optimization of antioxidant
      capacity, total phenolic content and extraction yield. Both quantitative modeling
      and response surface methodology suggested that methanol to water ratio percent
      and extraction temperature were the most effective parameters of UAE process.
      However, sonication time was found out to be an insignificant factor in
      ultrasound-assisted extraction of antioxidant and total phenolic compounds of O.
      basilicum. The optimum conditions were determined as temperature of 59  degrees
      C, methanol to water ratio of 65.2% (v/v), and extraction time of 20 min.

PMID- 26213051
TI  - Heavy metal accumulation and toxicity in smoothhound (Mustelus mustelus) shark
      from Langebaan Lagoon, South Africa.
AB  - Together with several health benefits, fish meat could introduce toxins to
      consumers in the form of heavy metal contaminants. High levels of mercury (Hg),
      especially, are frequently detected in certain predatory fish species. Mustelus
      mustelus fillets were analysed for 16 metals and three individual Hg species
      (inorganic Hg, ehtylmercury, methylmercury) with inductively coupled plasma mass
      spectrometry (ICP-MS) and HPLC-ICP-MS respectively. Eleven of the 30 sharks had
      total Hg levels above the maximum allowable limit with toxic methylmercury found
      as the dominant mercury species with a strong correlation (r = 0.97; p < 0.001)
      to total mercury concentrations. Limited correlations between metals and shark
      size parameters were observed; therefore metal accumulation in M. mustelus is
      mostly independent of size/age. Average values for arsenic (28.31 +/- 18.79
      mg/kg) exceed regulatory maximum limits and Hg (0.96 +/- 0.69 mg/kg) is close to
      the maximum limit with all other metals well below maximum limits.

PMID- 26213052
TI  - Metabolic profiling of a range of peach fruit varieties reveals high metabolic
      diversity and commonalities and differences during ripening.
AB  - Peach (Prunus persica) fruits from different varieties display differential
      organoleptic and nutritional properties, characteristics related to their
      chemical composition. Here, chemical biodiversity of peach fruits from fifteen
      varieties, at harvest and after post-harvest ripening, was explored by gas
      chromatography-mass spectrometry. Metabolic profiling revealed that metabolites
      involved in organoleptic properties (sugars, organic and amino acids), stress
      tolerance (raffinose, galactinol, maltitol), and with nutritional properties
      (amino, caffeoylquinic and dehydroascorbic acids) displayed variety-dependent
      levels. Peach varieties clustered into four groups: two groups of early-harvest
      varieties with higher amino acid levels; two groups of mid- and late-harvest
      varieties with higher maltose levels. Further separation was mostly dependent on
      organic acids/raffinose levels. Variety-dependent and independent metabolic
      changes associated with ripening were detected; which contribute to chemical
      diversity or can be used as ripening markers, respectively. The great variety
      dependent diversity in the content of metabolites that define fruit quality
      reinforces metabolomics usage as a tool to assist fruit quality improvement in
      peach. 

PMID- 26213053
TI  - An enhanced electrochemical platform based on graphene oxide and multi-walled
      carbon nanotubes nanocomposite for sensitive determination of Sunset Yellow and
      Tartrazine.
AB  - A novel electrochemical platform was designed for the simultaneous determination
      of Sunset Yellow (SY) and Tartrazine (TT), synthetic food dyes, by combining the
      signal amplification properties of graphene oxide (GO) and the excellent
      electronic and antifouling properties of multi-walled carbon nanotubes (MWCNTs).
      Stable dispersion of GO/MWCNTs composite was produced by sonication mixing.
      Compared with glassy carbon, MWCNTs and GO electrodes, GO/MWCNTs electrode
      exhibited strong enhancement effect and greatly increased the oxidation signal of
      SY and TT. Under optimized conditions, the enhanced anodic peak currents
      represented the excellent analytical performance of simultaneous detection of SY
      and TT in the range of 0.09-8.0 MUM, with a low limit of detection of 0.025 MUM
      for SY and 0.01 MUM for TT (S/N = 3), respectively. To further validate its
      possible application, the proposed method was successfully used for the
      determination of SY and TT in orange juice with satisfactory results.

PMID- 26213054
TI  - New grape stems-based liqueur: Physicochemical and phytochemical evaluation.
AB  - A number of traditional liqueurs are obtained by maceration of red fruits in
      aqueous ethanol liquor, namely sloe berries or sour cherry. On the other hand,
      the exploration of residual plant material derived from the winery industry
      (grape (Vitis vinifera L.) stems), which has been regarded as an interesting
      source of colored and uncolored (poly)phenols, could lead to an industrial
      alternative to the traditional distilled spirits produced, with valuable
      physicochemical and phytochemical properties. In the present work, vinification
      residues (grape stems) were used to produce a new beverage. The evaluation of the
      physic-chemical characteristics and phytochemical composition as well as the
      evolution of the determined parameters during maceration (90 and 180 days)
      allowed a number of interesting bioactive compounds to be identified. This new
      beverage is a liqueur with a high retention of phenolic compounds (ortho
      diphenols, flavanols, flavonols, and anthocyanins), with interesting physic
      chemical characteristics, that revealed significant antioxidant activity.

PMID- 26213055
TI  - Maillard reaction products in bread: A novel semi-quantitative method for
      evaluating melanoidins in bread.
AB  - The aim of this study was to test the methods currently in use and to develop a
      new protocol for the evaluation of melanoidins in bread. Markers of the early and
      advanced stages of the Maillard reaction were also followed in the crumb and the
      crust of bread throughout baking, and in a crust model system. The crumb of the
      bread contained N(epsilon)-fructoselysine and N(epsilon)-carboxymethyllysine but
      at levels 7 and 5 times lower than the crust, respectively. 5
      Hydroxymethylfurfural was detected only in the crust and its model system. The
      available methods for the semi-quantification of melanoidins were found to be
      unsuitable for their analysis in bread. Our new method based on size exclusion
      chromatography and fluorescence measures soluble fluorescent melanoidins in
      bread. These melanoidin macromolecules (1.7-5.6 kDa) were detected intact in both
      crust and model system. They appear to contribute to the dietary fibre in bread.

PMID- 26213056
TI  - The mechanism of hydrothermal hydrolysis for glycyrrhizic acid into
      glycyrrhetinic acid and glycyrrhetinic acid 3-O-mono-beta-D-glucuronide in
      subcritical water.
AB  - To improve the bioactivity and sweetness properties of glycyrrhizic acid (GL),
      the hydrothermal hydrolysis of GL into glycyrrhetinic acid (GA) and
      glycyrrhetinic acid 3-O-mono-beta-D-glucuronide (GAMG) in subcritical water was
      investigated. The effects of temperature, time and their interaction on the
      conversion ratios were analyzed and the reactions were elaborated with kinetics
      and thermodynamics. The results showed that GL hydrothermal hydrolysis was
      significantly (P < 0.05) affected by reaction time and temperature, as well as
      their interaction, and could be fitted into first-order kinetics. The
      thermodynamic analysis indicated that the hydrolysis of GL was endergonic and non
      spontaneous. The hydrolytic pathways were composed of complex consecutive and
      parallel reactions. It was concluded that subcritical water may be a potential
      medium for producing GAMG and GA.

PMID- 26213057
TI  - Inhibitory effect of rice bran extracts and its phenolic compounds on polyphenol
      oxidase activity and browning in potato and apple puree.
AB  - Full-fatted and commercially defatted rice bran extracts (RBE and CDRBE) were
      evaluated for their ability to inhibit enzymatic browning in potato and apple.
      RBE showed more effective inhibition of polyphenol oxidase (PPO) activity and
      browning in potato and apple as compared to CDRBE. Five phenolic compounds in RBE
      and CDRBE (protocatechuic acid, vanillic acid, p-coumaric acid, ferulic acid and
      sinapic acid) were identified by HPLC. They were then evaluated for their
      important role in the inhibition using a model system which found that ferulic
      acid in RBE and p-coumaric acid in CDRBE were active in enzymatic browning
      inhibition of potato and apple. p-Coumaric acid exhibited the highest inhibitory
      effect on potato and apple PPO (p ? 0.05). Almost all phenolic compounds showed
      higher inhibitory effect on potato and apple PPO than 100 ppm citric acid.

PMID- 26213058
TI  - Influence of encapsulated functional lipids on crystal structure and chemical
      stability in solid lipid nanoparticles: Towards bioactive-based design of
      delivery systems.
AB  - We investigated the influence of physicochemical properties of encapsulated
      functional lipids--vitamin A, beta-carotene and omega-3 fish oil--on the
      structural arrangement of solid lipid nanoparticles (SLN). The relationship
      between the crystal structure and chemical stability of the incorporated
      bioactive lipids was evaluated with different emulsifier compositions of a
      saponin-rich, food-grade Quillaja extract alone or combined with high-melting or
      low-melting lecithins. The major factors influencing the structural arrangement
      and chemical stability of functional lipids in solid lipid dispersions were their
      solubility in the aqueous phase and their crystallization temperature in relation
      to that of the carrier lipid. The results showed that the stabilization of the
      alpha-subcell crystals in the lattice of the carrier lipid is a key parameter for
      forming stable solid lipid dispersions. This study contributes to a better
      understanding of SLN as a function of the bioactive lipid.

PMID- 26213059
TI  - Rapid and non-destructive identification of water-injected beef samples using
      multispectral imaging analysis.
AB  - Water-injected beef has aroused public concern as a major food-safety issue in
      meat products. In the study, the potential of multispectral imaging analysis in
      the visible and near-infrared (405-970 nm) regions was evaluated for identifying
      water-injected beef. A multispectral vision system was used to acquire images of
      beef injected with up to 21% content of water, and partial least squares
      regression (PLSR) algorithm was employed to establish prediction model, leading
      to quantitative estimations of actual water increase with a correlation
      coefficient (r) of 0.923. Subsequently, an optimized model was achieved by
      integrating spectral data with feature information extracted from ordinary RGB
      data, yielding better predictions (r = 0.946). Moreover, the prediction equation
      was transferred to each pixel within the images for visualizing the distribution
      of actual water increase. These results demonstrate the capability of
      multispectral imaging technology as a rapid and non-destructive tool for the
      identification of water-injected beef.

PMID- 26213060
TI  - Development and validation of a UHPLC-HR-Orbitrap-MS method for the simultaneous
      determination of androstenone, skatole and indole in porcine meat and meat
      products.
AB  - Boar taint is an off-odour that entails negative consumer reactions. In this
      study two extraction and UHPLC-HRMS analysis methods, valuable for evaluation of
      consumer acceptance towards boar meat, were developed for quantification of
      indole, skatole, and androstenone in different meat products. Sample pretreatment
      consisted of extraction with methanol and a homogenising step (cooked ham, minced
      meat, tenderloin, bacon, cutlets, blade loin, uncooked ham) or a melting step
      (salami sausage and liver paste). Both methods were validated according to CD
      2002/657/EC and ISO 17025 guidelines. Good performance characteristics were
      obtained. Good linearity (R(2) ? 0.99) and no lack of fit was observed (95%
      confidence interval; F-test, p > 0.05). Also good recovery (89-110%) and
      satisfactory precision: repeatability (RSD ? 14.9%) and within-laboratory
      reproducibility (RSD ? 17.2%) were obtained. Analysis of cooked ham and salami
      sausage samples proved the applicability of both methods for routine analysis.

PMID- 26213061
TI  - Determination of clenbuterol in pork and potable water samples by molecularly
      imprinted polymer through the use of covalent imprinting method.
AB  - A novel molecularly imprinted polymer (MIP) for efficient separation and
      concentration of clenbuterol (CLB) was synthesized by covalent imprinting
      approach using CLB derivative as functional monomer. The MIPs synthesized were
      characterized by scanning electron microscope, nitrogen adsorption analysis,
      Fourier transform infrared spectrometer, and thermo-gravimetric analysis. The
      binding experimental results showed that the MIPs synthesized had fast adsorption
      kinetic (20 min at 25 mg L(-1)), high adsorption capacity and specific
      recognition ability for the analyte. In addition, the MIPs synthesized were
      successfully used as solid-phase sorbent for CLB sample preparation to be
      analyzed by high performance liquid chromatography with ultraviolet detector.
      Under optimized experimental conditions, the linear range of the calibration
      curve was 5-80 MUg L(-1) (R(2) = 0.9938). The proposed method was also applied to
      the analysis of CLB in pork and potable water samples.

PMID- 26213062
TI  - Production and concentration of monoacylglycerols rich in omega-3 polyunsaturated
      fatty acids by enzymatic glycerolysis and molecular distillation.
AB  - Production of monoacylglycerols (MAGs) rich in omega-3 polyunsaturated fatty
      acids (n-3 PUFAs) was conducted through short path distillation (SPD) of an
      acylglycerol mixture (containing 67% MAGs) produced by enzymatic glycerolysis of
      sardine oil with glycerol. A stepwise SPD process in a UIC KDL 5 system (vacuum
      10(-3)mbar, feeding flow 1.0 mL/min) was proceeded: the first distillation
      performed at evaporator temperature (TE) of 110  degrees C to remove glycerol
      completely and most of FFAs; and the second distillation at optimized TE 155 
      degrees C; resulting in a stream distillate with 91% purity and 94% overall
      recovery of MAGs. This work also demonstrated that SPD is able to concentrate n-3
      PUFAs in MAG form by distilling at proper TE e.g. 125  degrees C, where n-3 PUFAs
      are concentrated in the residues. Moreover, this work mapped out a complete
      processing diagram for scalable production of n-3 PUFAs enriched MAGs as
      potential food emulsifier and ingredient.

PMID- 26213063
TI  - Modeling of the lycopene extraction from tomato pulps.
AB  - The inputs of this network were the concentration of pectinase and time of
      incubation, and the outputs were extracted lycopene and the activity of radical
      scavenging activity. Two different networks were designed for the process under
      the sonication and without it. For optimal network, networks' transfer functions
      and different learning algorithms were evaluated and the validity of each one was
      determined. Consequently, the feedforward neural network with function of
      logarithmic transfer, Levenberg Marquardt algorithm and 4 neurons in the hidden
      layer with the correlation coefficient of 0.96 and 0.99 were respectively
      observed for the treatments under sonication and without it, furthermore, root
      mean squared error and standard error values were obtained 0.46 and 0.22
      respectively for the treatments under sonication and 0.77 and 0.38 without it as
      respectively optimal networks. The selected networks could determine the chosen
      responses, individually and in combined effect of both inputs as well (R(2) >
      0.98).

PMID- 26213064
TI  - Functional improvements in bovine serum albumin-fucoidan conjugate through the
      Maillard reaction.
AB  - The solubility, thermal stability, surface activity and emulsifying properties of
      native bovine serum albumin (BSA), heat-treated BSA, a BSA-fucoidan mixture, and
      a BSA-fucoidan conjugate were assessed. Covalent linkage of BSA with fucoidan
      resulted in significantly (p < 0.05) high solubility after heating at 90  degrees
      C for 15 min, particularly at pH 5. The BSA-fucoidan conjugate had a high melting
      temperature (97.09 +/- 1.45  degrees C), as found by differential scanning
      calorimetry, indicating strong heat stability and high resistance to
      denaturation. Although the attachment of fucoidan, a non-surface-active
      hydrophilic polysaccharide, gave no change in the surface activity, the
      emulsifying activity and the emulsion stability of the conjugate at pH 5 were
      superior to those of native BSA, heat-treated BSA, and the BSA-fucoidan mixture.
      Conclusively, fucoidan attachment enhanced the solubility, thermal stability and
      emulsifying properties of the protein molecules with negative charge distribution
      and steric stabilization.

PMID- 26213065
TI  - Development and validation of a modified QuEChERS protocol coupled to LC-MS/MS
      for simultaneous determination of multi-class antibiotic residues in honey.
AB  - LC-MS/MS assay was developed and validated according to EU guidelines for
      determination of nitrofuran metabolites and nitroimidazole residues in honey.
      Crude samples were acid-treated to liberate matrix-bound residues and a modified
      QuEChERS protocol was employed. Nitrofurantoin, furazolidone, furaltadone and
      nitrofurazone were determined via analysis of their metabolites AHD, AOZ, AMOZ
      and SEM, respectively while nitroimidazole residues; ronidazole (RNZ) and
      dimetridazole (DMZ) were determined directly. For all analytes, neat standard
      calibration curves, after correction for matrix effect were successfully
      employed. Decision limit (CCalpha) and detection capability (CCbeta) were below
      the MRPL for nitrofurans (1.00 MUg kg(-1)) and the recommended concentration for
      nitroimidazole (3.00 MUg kg(-1)), respectively. The CCalpha, CCbeta, percentage
      recovery and CV% ranges were 0.12-0.74 MUg kg(-1), 0.21-1.27 MUg kg(-1), 90.96
      104.80% and 2.65-12.58%, respectively. This work is part of the national
      initiative for establishing a national monitoring program for drug residues in
      Egyptian honey.

PMID- 26213066
TI  - Comparison of the effects of different heat treatment processes on rheological
      properties of cake and bread wheat flours.
AB  - Dry and hydrothermal heat treatments are efficient for modifying the
      technological-functional and shelf-life properties of wheat milling products. Dry
      heat treatment process is commonly used to enhance the volume of cakes.
      Hydrothermal heat treatment makes wheat flours suitable as thickener agents. In
      this study, cake and bread wheat flours that differed in baking properties were
      exposed to dry (100  degrees C, 12 min) and hydrothermal (95  degrees C, 5 min, 5
      20 l/h water) heat treatments. Rheological differences caused by the treatments
      were investigated in a diluted slurry and in a dough matrix. Dry heat treatment
      resulted in enhanced dough stability. This effect was significantly higher in the
      cake flour than the bread flour. Altered viscosity properties of the bread flour
      in the slurry matrix were also observed. The characteristics of hydrothermally
      treated samples showed matrix dependency: their viscosity increases in the slurry
      and decreases in the dough matrix. These results can support us to produce flour
      products with specific techno-functional properties.

PMID- 26213067
TI  - Isolation and characterization of fish scale collagen from tilapia (Oreochromis
      sp.) by a novel extrusion-hydro-extraction process.
AB  - Collagen is highly valued both as a food additive and a functional food
      ingredient. It is generally extracted by treatments with acid or alkali, enzyme,
      and microorganisms. However these methods are generally batch type, time-, energy
      , reactant-, and cost-consuming. Extrusion is widely used in the food industry,
      and offers many advantages, such as ease of operation, continuous production,
      high yield, and little waste. In this study, we developed a novel extrusion-hydro
      extraction (EHE) process for extraction of collagen from tilapia fish scale.
      Extruded scale samples had a 2-3 times higher protein extraction yield than that
      of non-extruded scale samples. All extracts contained hydroxyproline (61-73
      residues/1000 residues) and hydroxylysine (5-6 residues/1000 residues) and were
      identified as type-I collagens by FTIR, SDS-PAGE, and molecular weight
      distribution analyses. The physicochemical studies revealed that extracted
      collagens could have promising applications in the food, medical, and cosmetic
      industries.

PMID- 26213068
TI  - Application of isothermal titration calorimeter for screening bitterness
      suppressing molecules of quinine.
AB  - Bitterness-suppressing molecules have drawn ever-increasing attention these years
      for some unique advantages like low molecular weight, tastelessness and no
      interference on drug bioavailability. L-Arg was reported to suppress the
      bitterness of quinine, and we happened to find that the suppressing effects could
      be demonstrated by isothermal titration calorimeter (ITC). In this study, we
      investigated the possibility of using ITC to screen bitterness-suppressing
      molecules for quinine. Among the amino acids we screened, L-Lys bond quinine with
      high affinity. The results of ITC correlated well with the results of human
      sensory experiments. L-Arg and L-Lys could suppress the bitterness of quinine
      while other amino acids could not. Therefore, ITC has the potential to screen
      bitterness-suppressing molecules.

PMID- 26213069
TI  - Microencapsulation of H. pluvialis oleoresins with different fatty acid
      composition: Kinetic stability of astaxanthin and alpha-tocopherol.
AB  - Haematococcus pluvialis is a natural source of astaxanthin (AX). However, AX
      loses its natural protection when extracted from this microalga. In this study, a
      supercritical fluid extract (SFE) of H. pluvialis was obtained and added to oils
      with different fatty acid compositions (sunflower oil (SO) or high oleic
      sunflower oil (HOSO)). The oleoresins of H. pluvialis ((SO+SFE) and (HOSO+SFE))
      were encapsulated with Capsul by spray drying. The stability of the oleoresins
      and powders were studied at 40, 50 and 70 degrees  C. AX and alpha-tocopherol
      (AT) degradation followed a zero-order and first-order kinetic model,
      respectively, for all systems. The encapsulation of oleoresins improved the
      stability of AX and AT to a greater extent in oleoresins with a monounsaturated
      fatty acid profile, as shown by the significantly lowest degradation rate
      constants and longest half-lives. Therefore, the encapsulation of H. pluvialis
      oleoresins is an alternative to developing a functional ingredient for healthy
      food design.

PMID- 26213070
TI  - Antiglycation activity of lipophilized epigallocatechin gallate (EGCG)
      derivatives.
AB  - Lipophilized EGCG derivatives were synthesized by esterification of EGCG with
      aliphatic fatty acids and demonstrated to possess many advantages, such as higher
      lipophilicity and apparent health benefits over the parent EGCG. This study used
      a total of seven lipophilized EGCG derivatives with fatty acids of different
      chain lengths attached and examined the impact of lipophilization on EGCG's
      antiglycation activity in vitro. The length of fatty acid chain was found to be
      an important factor, which positively correlated with ABTS radical scavenging
      capacity but long chain bulky substitutes prevented methylglyoxal (MGO) trapping.
      Except docosahexaenoic acid (DHA), lipophilization generally showed no
      interference with EGCG's in vitro inhibitory activity of advanced glycation
      endproducts (AGEs) formation. Therefore, the lipophilized EGCG derivatives are
      promising candidates worthy of further exploration for preventing AGEs
      accumulation in vivo and hence treating AGEs-associated diseases. 

PMID- 26213071
TI  - Sugar and acid content of Citrus prediction modeling using FT-IR fingerprinting
      in combination with multivariate statistical analysis.
AB  - A high-throughput screening system for Citrus lines were established with higher
      sugar and acid contents using Fourier transform infrared (FT-IR) spectroscopy in
      combination with multivariate analysis. FT-IR spectra confirmed typical spectral
      differences between the frequency regions of 950-1100 cm(-1), 1300-1500 cm(-1),
      and 1500-1700 cm(-1). Principal component analysis (PCA) and subsequent partial
      least square-discriminant analysis (PLS-DA) were able to discriminate five Citrus
      lines into three separate clusters corresponding to their taxonomic
      relationships. The quantitative predictive modeling of sugar and acid contents
      from Citrus fruits was established using partial least square regression
      algorithms from FT-IR spectra. The regression coefficients (R(2)) between
      predicted values and estimated sugar and acid content values were 0.99. These
      results demonstrate that by using FT-IR spectra and applying quantitative
      prediction modeling to Citrus sugar and acid contents, excellent Citrus lines can
      be early detected with greater accuracy.

PMID- 26213072
TI  - An efficient approach to the quantitative analysis of humic acid in water.
AB  - Rayleigh and Raman scatterings inevitably appear in fluorescence measurements,
      which make the quantitative analysis more difficult, especially in the overlap of
      target signals and scattering signals. Based on the grayscale images of three
      dimensional fluorescence spectra, the linear model with two selected Zernike
      moments was established for the determination of humic acid, and applied to the
      quantitative analysis of the real sample taken from the Yellow River. The
      correlation coefficient (R(2)) and leave-one-out cross validation correlation
      coefficient (R(2)cv) were up to 0.9994 and 0.9987, respectively. The average
      recoveries were reached 96.28%. Compared with N-way partial least square and
      alternating trilinear decomposition methods, our approach was immune from the
      scattering and noise signals owing to its powerful multi-resolution
      characteristic and the obtained results were more reliable and accurate, which
      could be applied in food analyses. 

PMID- 26213073
TI  - A new specific reference gene based on growth hormone gene (GH1) used for
      detection and relative quantification of Aquadvantage(r) GM salmon (Salmo salar
      L.) in food products.
AB  - Genetic transformation of fish is mainly oriented towards the improvement of
      growth for the benefit of the aquaculture. Actually, Atlantic salmon (Salmo
      salar) is the species most transformed to achieve growth rates quite large
      compared to the wild. To anticipate the presence of contaminations with GM salmon
      in fish markets and the lack of labeling regulations with a mandatory threshold,
      the proper methods are needed to test the authenticity of the ingredients. A
      quantitative real-time polymerase chain reaction (QRT-PCR) method was used in
      this study. Ct values were obtained and validated using 15 processed food
      containing salmon. The relative and absolute limits of detection were 0.01% and
      0.01 ng/MUl of genomic DNA, respectively. Results demonstrate that the developed
      QRT-PCR method is suitable specifically for identification of S. salar in food
      ingredients based on the salmon growth hormone gene 1 (GH1). The processes used
      to develop the specific salmon reference gene case study are intended to serve as
      a model for performing quantification of Aquadvantage(r) GM salmon on future
      genetically modified (GM) fish to be commercialized.

PMID- 26213074
TI  - Novel identification strategy for ground coffee adulteration based on UPLC-HRMS
      oligosaccharide profiling.
AB  - Coffee is one of the most common and most valuable beverages. According to
      International Coffee Organization (ICO) reports, the adulteration of coffee for
      financial reasons is regarded as the most serious threat to the sustainable
      development of the coffee market. In this work, a novel strategy for adulteration
      identification in ground coffee was developed based on UPLC-HRMS oligosaccharide
      profiling. Along with integrated statistical analysis, 17 oligosaccharide
      composition were identified as markers for the identification of soybeans and
      rice in ground coffee. This strategy, validated by manual mixtures, optimized
      both the reliability and authority of adulteration identification. Rice and
      soybean adulterants present in ground coffee in amounts as low as 5% were
      identified and evaluated. Some commercial ground coffees were also successfully
      tested using this strategy. 

PMID- 26213075
TI  - Low hygroscopic spray-dried powders with trans-glycosylated food additives
      enhance the solubility and oral bioavailability of ipriflavone.
AB  - The improvement in the solubility and dissolution rate may promote a superior
      absorption property towards the human body. The spray-dried powders (SDPs) of
      ipriflavone, which was used as a model hydrophobic flavone, with trans
      glycosylated rutin (Rutin-G) showed the highest solubilizing effect of
      ipriflavone among three types of trans-glycosylated food additives. The SDPs of
      ipriflavone with Rutin-G have both a significant higher dissolution rate and
      solubility enhancement of ipriflavone. This spray-dried formulation of
      ipriflavone with Rutin-G exhibited a low hygroscopicity as a critical factor in
      product preservation. In addition, an improvement in the oral absorption of
      ipriflavone was achieved by means of preparing composite particles of
      ipriflavone/Rutin-G via spray drying, indicating a 4.3-fold increase in the area
      under the plasma concentration-time curve compared with that of untreated
      ipriflavone. These phenomena could be applicable to food ingredients involving
      hydrophobic flavones for producing healthy food with a high quality. 

PMID- 26213076
TI  - Relationship between antioxidant status and oxidative stability in lamb meat
      reinforced with dietary rosemary diterpenes.
AB  - The relationship between the antioxidant status of fresh meat and oxidative
      stability of chilled-packed meat obtained from lambs fed on a diet supplemented
      with two different doses of a rosemary extract containing carnosic acid and
      carnosol was studied. The incorporation of rosemary extract in the lamb diet led
      to the deposition of functional levels of the diterpenic metabolite C19H22O3 in
      meat, which improved its stability against oxidation. The antioxidant status
      could be assessed through both the radical scavenging capacity (DPPH and TEAC)
      and the ferric reducing antioxidant power (FRAP). In general, antioxidant status
      values correlated better (P < 0.05) with the changes in CIELAB colour,
      malondialdehyde and sensory scoring than with the changes in hexanal and protein
      carboxylation measured in the lamb cuts kept under protective atmosphere for up
      to 14 days. The FRAP and DPPH assays were more suitable than the TEAC assay for
      predicting meat oxidation and any resulting discolouration and rancidity.

PMID- 26213077
TI  - Contemporary carbon content of bis (2-ethylhexyl) phthalate in butter.
AB  - The fraction of naturally produced bis (2-ethylhexyl) phthalate (DEHP), a
      ubiquitous plasticizer known to contaminate packaged foods, was determined for
      each of five 1.10 kg samples of unsalted market butter by accelerator mass
      spectrometry (AMS). After extraction and concentration enrichment with liquid
      liquid extraction, flash column chromatography, and preparative-scale high
      performance liquid chromatography, each sample provided ~ 250 MUg extracts of
      DEHP with carbon purity ranging from 92.5 +/- 1.2% (n = 3, 1sigma) to 97.1 +/-
      0.8% (n = 3, 1sigma) as measured with gas chromatography mass spectrometry (GC
      MS). After corrections for method blank DEHP, co-eluting compounds, and
      unidentified carbon, the mean fraction of naturally produced DEHP in butter was
      determined to be 0.16 +/- 0.12 (n = 5, 1sigma). To our knowledge, this is the
      first report of the contemporary fraction of DEHP isolated from market butter in
      the U.S.

PMID- 26213078
TI  - Antioxidant effects of gastrointestinal digested purple carrot extract on the
      human cells of colonic mucosa.
AB  - Purple carrot (PC) is a potential dietary constituent, which represents a
      valuable source of antioxidants and can modulate the reactive oxygen species
      (ROS) level in the gastrointestinal tract. Antioxidant capacity of a PC extract
      subjected to digestion process simulated in the artificial alimentary tract,
      including the stomach, small intestine and colon, was analyzed in normal human
      cells of colon mucosa. Results indicated that the extract obtained upon passage
      through the gastrointestinal tract, which could come into contact with the
      colonic cells in situ, was less potent than the extract, which was not subjected
      to digestion process. Digested PC extract exhibited intracellular ROS-inhibitory
      capacity, with 1mg/mL showing the ROS clearance of 18.4%. A 20.7% reduction in
      oxidative DNA damage due to colon mucosa cells' treatment with digested PC
      extract was observed. These findings indicate that PC extract is capable of
      colonic cells' protection against the adverse effects of oxidative stress. 

PMID- 26213079
TI  - Cost-efficient entrapment of beta-glucosidase in nanoscale latex and silicone
      polymeric thin films for use as stable biocatalysts.
AB  - beta-Glucosidase is an ubiquitous enzyme which has enormous biotechnological
      applications. Its deficiency in natural enzyme preparations is often overcome by
      exogenous supplementation, which further increases the enzyme utilization cost.
      Enzyme immobilization offers a potential solution through enzyme recycling and
      easy recovery. In the present work Aspergillus niger beta-glucosidase is
      immobilized within nanoscale polymeric materials (polyurethane, latex and
      silicone), through entrapment, and subsequently coated onto a fibrous support.
      Highest apparent activity (90 U g(-1) polymer) was observed with latex, while
      highest entrapment efficiency (93%) was observed for the silicone matrix.
      Immobilization resulted in the thermo-stabilization of the beta-glucosidase with
      an increase in optimum temperature and activation energy for cellobiose
      hydrolysis. Supplementation to cellulases also resulted in an increased cellulose
      hydrolysis, while retaining more than 70% functional stability. Hence, the
      current study describes novel preparations of immobilized beta-glucosidase as
      highly stable and active catalysts for industrial food- and bio-processing
      applications.

PMID- 26213080
TI  - Development and validation of an analytical method for the determination of 4
      hexylresorcinol in food.
AB  - This study presents a method validation for extraction and quantitative analysis
      of 4-hexylresorcinol residues in shrimp and crab meat using HPLC-FLD. We were
      focused on the collaboratively analysis of each shrimp and crab meat samples, and
      developed LC-MS/MS method for the correct confirmation of the identity of
      compound. Validation parameters; selectivity, linearity, LOD, LOQ, accuracy,
      precision, and measurement of uncertainty were attained. The measurement of
      uncertainty was based on the precision study, data related to the performance of
      the analytical process and quantification of 4-hexylresorcinol. For HPLC-FLD
      analysis, the recoveries of 4-hexylresorcinol from spiked samples at levels of
      0.2-10.0 ppm ranged from 92.54% to 97.67% with RSDs between 0.07% and 1.88%.
      According to these results, the method has been proven to be appropriate for
      extraction and determination of 4-hexylresorcinol, and can be used to maintain
      the safety of shrimp and crab products containing 4-hexylresorcinol residues.

PMID- 26213081
TI  - Prosopis alba exudate gum as excipient for improving fish oil stability in
      alginate-chitosan beads.
AB  - The aim of the present work was to employ an exudate gum obtained from a South
      American wild tree (Prosopis alba), as wall material component to enhance the
      oxidative stability of fish oil encapsulated in alginate-chitosan beads. For this
      purpose, beads were vacuum-dried and stored under controlled conditions.
      Oxidation products, fatty acid profiles and lipid health indices were measured
      during storage. Alginate-chitosan interactions and the effect of gum were
      manifested in the FT-IR spectra. The inclusion of the gum in the gelation media
      allowed decreasing the oxidative damage during storage in comparison to the free
      oil and alginate-chitosan beads. The gum also improved wall material properties,
      providing higher oil retention during the drying step and subsequent storage.
      Fatty acids quality and lipid health indices were widely preserved in beads
      containing the gum. Present results showed a positive influence of the gum on oil
      encapsulation and stability, being the main mechanism attributed to a physical
      barrier effect. 

PMID- 26213082
TI  - Functionalities of conjugated compounds of gamma-aminobutyric acid with
      salicylaldehyde or cinnamaldehyde.
AB  - Aldehydes or ketones can react with amino compounds to form Schiff base adducts,
      which have been widely studied and shown to exhibit antimicrobial, antioxidant or
      antiviral activity. Salicylaldehyde (SA) and cinnamaldehyde (CA) are components
      of plant essential oils. gamma-Aminobutyric acid (GA) is an important substance
      in the mammalian central nervous system and responsible for many bioactivities.
      This study aimed to synthesize functional Schiff base adducts using GA and SA or
      CA; to study the antimicrobial activity, antioxidant activity and tyrosinase
      inhibition activity of these adducts (SA-GA and CA-GA) and their metal complexes-
      SA-GA-Cu (or Zn) and CA-GA-Cu (or Zn); and to find their applications in food
      systems. SA-GA and CA-GA both exhibited good antibacterial effects, and so did
      their Cu complexes. As for antioxidant activity, SA-GA and CA-GA were superior to
      their metal complexes in most tests. Regarding inhibition of enzymatic browning
      of mushrooms, both SA-GA-Cu and CA-GA-Cu could inhibit tyrosinase activity
      effectively.

PMID- 26213083
TI  - An evaluation of Fourier transforms infrared spectroscopy method for the
      classification and discrimination of bovine, porcine and fish gelatins.
AB  - The objective of this research was to develop a rapid spectroscopic technique as
      an alternative method for the differentiation and authentication of gelatin
      sources in food products by using attenuated total reflectance Fourier transform
      infrared (ATR-FTIR) spectra combined with chemometrics. Clear discrimination and
      classification of all the studied gelatin sources (bovine, porcine, and fish)
      were achieved by hierarchical cluster and principle component analysis (PCA).
      Amide-I (1700-1600 cm(-1)) and Amide-II (1565-1520 cm(-1)) spectral bands were
      used in a chemometric method. Moreover, ATR-FTIR spectral data successfully
      discriminated pure bovine gelatin from mixture of bovine and porcine gelatins,
      which is very important for the food industry. The method that we adopted could
      be beneficial for rapid, simple and economic determination of both gelatin
      presence and its origin from food products such as yogurt, ice cream, milk
      dessert or other gelatin containing products such as pharmaceuticals and
      cosmetics.

PMID- 26213084
TI  - Impact of different techniques involving contact with lees on the volatile
      composition of cider.
AB  - The effect of different treatments involving contact with natural lees on the
      aromatic profile of cider has been evaluated. Comparing with the untreated
      ciders, the contact with lees brought about a significant increase of the
      concentrations of most of the volatile compounds analysed, in particular fatty
      acids, alcohols, ethyl esters and 3-ethoxy-1-propanol. The opposite was observed
      among fusel acetate esters and 4-vinylguaiacol. The addition of beta-glucanase
      enhanced the increase of ethyl octanoate, but produced a decrease in the contents
      of decanoic acid and all of the major volatiles excepting acetaldehyde, ethyl
      acetate and acetoine, whereas the application of oxygen influenced the rise of
      the level of 3-ethoxy-1-propanol only. The olfactometric profiles also revealed
      significant effects of the treatment with lees for ethyl propionate, diacetyl,
      cis-3-hexenol, acetic acid, benzyl alcohol, and m-cresol, while the addition of
      oxygen significantly influenced the perception of ethyl hexanoate, 1-octen-3-one,
      3-methyl-2-butenol, t-3-hexenol and c-3-hexenol. 

PMID- 26213085
TI  - Organosulfide profile and hydrogen sulfide-releasing capacity of stinky bean
      (Parkia speciosa) oil: Effects of pH and extraction methods.
AB  - Stinky beans (Parkia speciosa) were hydrodistilled and solvent-extracted and the
      oil obtained was analyzed by GC-MS/FID. Nine cyclic and one acyclic
      organosulfides were identified comprising 36% of total volatiles. Solvent
      extracts contained significantly (p < 0.05) higher total organosulfides (680 ppm)
      as compared to distilled oil (444 ppm). The concentrations of organosulfides are
      highly dependent on the pH values of the matrix, with control sample (pH 5.40)
      giving the highest total organosulfides (424 ppm) followed by that of pH 7.0 (234
      ppm), pH 9.0 (195 ppm), and pH 3.0 (152 ppm). The H2S-releasing capacity,
      expressed as diallyl trisulfide equivalents (DATS-E in mmol DATS/g), corresponded
      well with the differences in organosulfide concentrations as affected by pH with
      control having the highest value (24.35) followed pH 7.0 (7.27), pH 9.0 (3.27),
      and pH 3.0 (1.80). We conclude that stinky bean oil is a potent H2S-releasing
      agent that could have health-beneficial properties.

PMID- 26213086
TI  - Recyclable non-ligand dual cloud point extraction method for determination of
      lead in food samples.
AB  - A new pH-mediated non-ligand dual cloud point extraction (NL-DCPE) was first
      developed for extraction Pb(II) from food samples. The NL-DCPE method includes
      two cloud point extraction (CPE) steps and the recycling of the copolymer. The
      first procedure was based on the forming of lead hydroxide at pH 9.5 and
      subsequent lead hydroxide was entrapped in a thermoseparating triblock copolymer
      [(PEO)10(PPO)23(PEO)10] (L44) phase. At second stage, the copolymer-rich phase
      was treated with the acidic solution, and Pb(II) was back extracted into the
      aqueous phase. So the problem emerging from the high viscosity of the copolymer
      rich phase can be well solved. Under the optimized conditions, the extraction
      efficiency of 97.20% and detection limit of 1.9 MUg L(-1) were obtained.
      Moreover, the copolymer L44 was successfully recycled and reused for more than
      two times. This method was successfully used for analyzing Pb(II) in food samples
      with satisfactory recoveries in the range of 94.01-101.19%.

PMID- 26213087
TI  - Effect of heat-processing on the antioxidant and prooxidant activities of beta
      carotene from natural and synthetic origins on red blood cells.
AB  - Extraction of bioactives is a cause of structural changes in these molecules. In
      this work, the bioactivity of commercial natural beta-carotenes, one softly
      extracted without heat-assistance from Momordica cochinchinensis (BCG), one
      conventionally extracted from another natural source (BCC), and a synthetic one
      (BCS), was assessed during an additional heat-treatment mimicking formulation.
      Their antioxidant activities were evaluated after heat-treatment at different
      concentrations through hemolysis of horse red blood cells. The thermal 15-cis
      isomerization of beta-carotene, characterized by DAD-HPLC, resulted in a 2.5- to
      4.8-fold increase in the anti-hemolytic effect but this was undetected in
      chemical assay, at 4 MUM. At 100 MUM, BCC lost its antioxidant properties and
      became pro-oxidant. This effect might be caused by long-chain-oxidized-products
      of BCC. Results demonstrated that a short heat-treatment improves the bioactivity
      of beta-carotene but longer treatments made BCC prooxidant, showing that samples
      that underwent drastic extraction processes could not tolerate additional steps
      for functional food production.

PMID- 26213088
TI  - Analysis of advanced glycation endproducts in selected food items by ultra
      performance liquid chromatography tandem mass spectrometry: Presentation of a
      dietary AGE database.
AB  - The aim of this study was to validate an ultra-performance liquid chromatography
      tandem mass-spectrometry (UPLC-MS/MS) method for the determination of advanced
      glycation endproducts (AGEs) in food items and to analyze AGEs in a selection of
      food items commonly consumed in a Western diet. N(epsilon)-(carboxymethyl)lysine
      (CML), N(epsilon)-(1-carboxyethyl)lysine (CEL) and N(delta)-(5-hydro-5-methyl-4
      imidazolon-2-yl)-ornithine (MG-H1) were quantified in the protein fractions of
      190 food items using UPLC-MS/MS. Intra- and inter-day accuracy and precision were
      2-29%. The calibration curves showed perfect linearity in water and food
      matrices. We found the highest AGE levels in high-heat processed nut or grain
      products, and canned meats. Fruits, vegetables, butter and coffee had the lowest
      AGE content. The described method proved to be suitable for the quantification of
      three major AGEs in food items. The presented dietary AGE database opens the
      possibility to further quantify actual dietary exposure to AGEs and to explore
      its physiological impact on human health. 

PMID- 26213089
TI  - Comparison of spray, freeze and oven drying as a means of reducing bitter
      aftertaste of steviol glycosides (derived from Stevia rebaudiana Bertoni plant)-
      Evaluation of the final products.
AB  - The aim of this study was to encapsulate the steviol glycosides (SGs) by spray,
      freeze and vacuum oven drying in order to minimise the bitter aftertaste of the
      SGs, as well as to improve their properties. Different ratios of maltodextrin to
      inulin as agents were examined, 80:20, 75:25, 70:30, 65:35 and 60:40, while the
      concentration of SGs in total solids was maintained constant at 2.5%. The
      obtained SGs products were evaluated by microencapsulation efficiency (MEE%),
      hygroscopicity, solubility, moisture content, structure (SEM, XRD), FT-IR and
      sensory properties. Significant differences in MEE%, moisture content, structure
      and solubility values were observed depending on the applied drying method. The
      reduced hygroscopicity values (20.26-26.67 g H2O/100g dry weight) contribute to
      improved stability. The FT-IR technique confirmed that SGs maintained their
      chemical integrity during the applied drying processes. The spray dried SGs
      products presented the best physicochemical characteristics and the most
      appealing sensorial ones.

PMID- 26213090
TI  - Phenolic compounds from yerba mate based beverages--A multivariate optimisation.
AB  - This work used a central composite design to optimise a reverse phase high
      performance liquid chromatographic method for the simultaneous separation of
      gallic, syringic, 5-caffeoylquinic, caffeic, p-coumaric, ferulic, 3,4
      dicaffeoylquinic, 3,5-dicaffeoylquinic, 4,5-dicaffeoylquinc acids, rutin in
      aqueous extracts of yerba mate (Ilex paraguariensis). The effect of the linear
      gradient time, the initial and the final methanol concentration in the mobile
      phase on the peak resolution and peak symmetry was evaluated. The 26 responses
      obtained were simultaneously optimised using the desirability method of Derringer
      and Suich. According to results, the increasing in the resolution and peak
      symmetry was achieved by using lesser levels of methanol in both initial and
      final gradient elution (-1.68, -1), as well as higher gradient times (+1, +1.68).
      The optimal condition (13.9-40% of methanol in 39.4 min) were successfully
      applied for analysis of chimarrao, terere and mate tea aqueous extracts, which
      showed as excellent sources of chlorogenic acids.

PMID- 26213091
TI  - Application and optimization of microwave-assisted extraction and dispersive
      liquid-liquid microextraction followed by high-performance liquid chromatography
      for sensitive determination of polyamines in turkey breast meat samples.
AB  - A novel method based on microwave-assisted extraction and dispersive liquid
      liquid microextraction (MAE-DLLME) followed by high-performance liquid
      chromatography (HPLC) was developed for the determination of three polyamines
      from turkey breast meat samples. Response surface methodology (RSM) based on
      central composite design (CCD) was used to optimize the effective factors in
      DLLME process. The optimum microextraction efficiency was obtained under
      optimized conditions. The calibration graphs of the proposed method were linear
      in the range of 20-200 ng g(-1), with the coefficient determination (R(2)) higher
      than 0.9914. The relative standard deviations were 6.72-7.30% (n = 7). The limits
      of detection were in the range of 0.8-1.4 ng g(-1). The recoveries of these
      compounds in spiked turkey breast meat samples were from 95% to 105%. The
      increased sensitivity in using the MAE-DLLME-HPLC-UV has been demonstrated.
      Compared with previous methods, the proposed method is an accurate, rapid and
      reliable sample-pretreatment method.

PMID- 26213092
TI  - Advances in characterisation and biological activities of chitosan and chitosan
      oligosaccharides.
AB  - Chitosan and chitosan oligosaccharides (COS) have been reported to possess
      various biomedical properties, including antimicrobial activities, immuno
      enhancing effects, and anti-tumour activities. COS have attracted considerable
      interest due to their physicochemical properties, and potential applications in
      the food and pharmaceutical industries, especially in cancer therapies. This
      paper describes the preparation of COS and their physicochemical properties, and
      modification, which aids understanding of their biological activities. Based on
      the latest reports, several biological and anti-tumour activities of COS will be
      discussed. The proposed anti-tumour mechanisms of COS are summarised, to provide
      comprehensive insights into research on the molecular level. Finally, the
      potential applications and future development of the biopolymer will be
      discussed. 

PMID- 26213093
TI  - Effects of chemical treatments on fresh-cut papaya.
AB  - Four treatments (control, 0.1% cinnamaldehyde, 0.75% calcium chloride and
      combination of 0.1% cinnamaldehyde and 0.75% calcium chloride) were used to
      evaluate chemical effects on shelf life, quality and sensory acceptability of
      fresh-cut papaya (Carica papaya L.). Papaya slices were packed and covered with
      polypropylene film, stored at 5  degrees C; and evaluated after 1, 3, 6, 9, 12,
      and 15 days for microbiological and physicochemical changes. A sensory evaluation
      was performed at 1, 3, 6, 9, and 12 days. There was no occurrence of Salmonella,
      Escherichia coli or psychotropic bacteria. The cinnamaldehyde alone and a
      combination of cinnamaldehyde and calcium chloride treatments yielded better
      control of the total coliforms. The combination treatment decreased the CO2
      concentration and increased the maintenance of papaya firmness. All the
      treatments had acceptability. The combination treatment was the most effective
      treatment for flavor, taste, and preservation until day 12.

PMID- 26213094
TI  - Biphenyl-2,4,6,3',5'-pentacarboxylic acid as a tecton for six new Co(II)
      coordination polymers: pH and N-donor ligand-dependent assemblies, structure
      diversities and magnetic properties.
AB  - Six new Co(ii)-based mixed-ligand coordination polymers, namely,
      [Co2(H3bppc)2(2,2'-bpy)4].H2O (), [Co2(Hbppc)(2,2'-bpy)2(H2O)].H2O (),
      [Co(H2bppc)(H-bpp)].2H2O (), [Co3(MU3-OH)(bppc)(dps)(CH3CH2OH)].4H2O (),
      [Co2(bppc)(bib)(H2O)4].(H2-bib)0.5.(H2O)3 (), and [Co2(Hbppc)(bix)2].2H2O (),
      (H5bppc = biphenyl-2,4,6,3',5'-pentacarboxylic acid, 2,2'-bpy = 2,2'-bipyridine,
      bpp = 1,3-bis(4-pyridyl)propane, dps = 4,4'-sulfanediyldipyridine, bib = 1,4
      bis(imidazol-1-yl)benzene, bix = 1,4-bis(imidazol-1-ylmethyl)benzene), have been
      obtained under solvothermal conditions. exhibits a 3D supramolecular framework
      based on a [Co2(H3bppc)2(2,2'-bpy)4] unit. has a (3,4)-connected dmc net with a
      (4.8(2))(4.8(5)) topology containing alternate binuclear metal clusters and
      single metal centres. shows a 3D supramolecular architecture constructed from
      ladder-like arrays decorated with H-bpp. exhibits a binodal (5,7)-connected 3D
      network based on trinuclear [Co3(MU3-OH)](5+) units with an unusual
      (3.4(6).5(2).6)(3(2).4(6).5(7).6(5).7) topology. features a (4,6)-connected 3D
      fsc open framework with binuclear [Co2(H2O)(COO)](3+) units as nodes, and H2-bib
      and water molecules located in the voids of its framework by hydrogen bonds.
      possesses a 3D net containing unusual 2D polyrotaxane sheets. Topological
      analysis reveals that has a (3,4,4)-connected 3D network with a
      (4.6.7(4))(4.6.7)(6.7(2).10(2).11) topology. The structural difference of and is
      due to the different pH values of the reaction system. Though complexes were
      synthesised under similar reaction conditions, the carboxylic groups of H5bppc
      were partially deprotonated in , and and fully deprotonated in and . Complexes
      display diverse structures depending on different N-donor ligands and the
      coordination modes of the multicarboxylate ligand. Variable-temperature magnetic
      susceptibility measurements reveal that complexes show antiferromagnetic
      interactions. 

PMID- 26213095
TI  - The PARK2/Parkin receptor on damaged mitochondria revisited-uncovering the role
      of phosphorylated ubiquitin chains.
AB  - Phosphorylated ubiquitin produced by PINK1 kinase functions as a PARK2/Parkin
      activator by derepressing intramolecular autoinhibition of PARK2 E3 activity.
      Unexpectedly, we revealed that phosphorylated polyubiquitin chain also functions
      in the PARK2 recruitment process as a PARK2 receptor. Phosphorylated ubiquitin
      enables us to comprehensively understand how PINK1 and PARK2 catalyzes (phospho
      )ubiquitination of depolarized mitochondria and subsequent mitophagy. 

PMID- 26213096
TI  - Exposure to negatively charged-particle dominant air-conditions on human
      lymphocytes in vitro activates immunological responses.
AB  - Indoor air-conditions may play an important role in human health. Investigation
      of house conditions that promote health revealed that negatively charged-particle
      dominant indoor air-conditions (NAC) induced immune stimulation. NAC was
      established using fine charcoal powder on walls and ceilings and utilizing forced
      negatively charged particles (approximate diameter: 20 nm) dominant in indoor air
      conditions created by applying an electric voltage (72 V) between the backside of
      the walls and the ground. We reported previously that these conditions induced a
      slight and significant increase of interleukin-2 during 2.5 h stay, and an
      increase of natural killer (NK) cell cytotoxicity, when examining human subjects
      after a two-week night stay under these conditions. In the present study, we
      investigated whether exposure to NAC in vitro affects immune conditions. Although
      the concentrations of particles were different, an incubator for cell culture
      with NAC was set and cellular compositions and functions of various freshly
      isolated human lymphocytes derived from healthy donors were assayed in the NAC
      incubator and compared with those of cultures in a standard (STD) incubator.
      Results showed that NAC cultivation caused an increase of CD25 and PD-1
      expressing cells in the CD4 positive fraction, enhancement of NK cell
      cytotoxicity, production of interferon-y (IFNgamma), and slight enhancement of
      regulatory T cell function. In addition, the formula designated as the "immune
      index" clearly differed between STD and NAC culture conditions. Thus, NAC
      conditions may promote human health through slight activation of the immune
      system against cancer cells and virus infection as shown by this in vitro study
      and our previously reported human studies.

PMID- 26213097
TI  - IL-2/IL-2 antibody immune complex regulates HSV-induced inflammation through
      induction of IL-2 receptor alpha, beta, and gamma in a mouse model.
AB  - The differences of serum IL-2 levels were not consistent between Behcet's Disease
      (BD) patients and healthy controls, however, the correlation of interleukin-2
      receptor (IL-2R) and BD has not been investigated. IL-2R is composed of three
      subunits; alpha, beta, and gamma. The expression frequencies of IL-2R subunits
      were analyzed in the peripheral blood mononuclear cells, spleens, and lymph node
      (LN) cells. The expression of IL-2R subunits was different between BD mice and
      controls. IL-2R beta expressing cell frequencies were also different between BD
      patients and healthy controls. The IL-2/anti-mIL-2 antibody complex
      administration regulated the IL-2R subunits in mice. The change of expression in
      IL-2R was accompanied by the increase of CD8+CD44+ memory T cells, CD3
      NK1.1+CD11b+CD27+ natural killer cells, and improvement of symptoms. In this
      study, we elucidated the role of IL-2R subunits on BD, a finding that can be
      connected to therapeutic strategy for patients based on the results from the
      treatment of BD mice.

PMID- 26213098
TI  - Effects of wind-energy facilities on breeding grassland bird distributions.
AB  - The contribution of renewable energy to meet worldwide demand continues to grow.
      Wind energy is one of the fastest growing renewable sectors, but new wind
      facilities are often placed in prime wildlife habitat. Long-term studies that
      incorporate a rigorous statistical design to evaluate the effects of wind
      facilities on wildlife are rare. We conducted a before-after-control-impact
      (BACI) assessment to determine if wind facilities placed in native mixed-grass
      prairies displaced breeding grassland birds. During 2003-2012, we monitored
      changes in bird density in 3 study areas in North Dakota and South Dakota
      (U.S.A.). We examined whether displacement or attraction occurred 1 year after
      construction (immediate effect) and the average displacement or attraction 2-5
      years after construction (delayed effect). We tested for these effects overall
      and within distance bands of 100, 200, 300, and >300 m from turbines. We observed
      displacement for 7 of 9 species. One species was unaffected by wind facilities
      and one species exhibited attraction. Displacement and attraction generally
      occurred within 100 m and often extended up to 300 m. In a few instances,
      displacement extended beyond 300 m. Displacement and attraction occurred 1 year
      after construction and persisted at least 5 years. Our research provides a
      framework for applying a BACI design to displacement studies and highlights the
      erroneous conclusions that can be made without the benefit of adopting such a
      design. More broadly, species-specific behaviors can be used to inform management
      decisions about turbine placement and the potential impact to individual species.
      Additionally, the avoidance distance metrics we estimated can facilitate future
      development of models evaluating impacts of wind facilities under differing land
      use scenarios. 

PMID- 26213099
TI  - Bis(azulene) "submarine" metal dimer sandwich compounds (C10H8)2M2(M = Ti, V, Cr,
      Mn, Fe, Co, Ni): Parallel and opposed orientations.
AB  - The opposed and parallel structures for the binuclear bis(azulene) "submarine"
      sandwiches (C10H8)2M2 (M = Ti, V, Cr, Mn, Fe, Co, Ni) have been optimized using
      density functional theory. The lowest energy (C10H8)2 M2 structures of the early
      transition metals Ti, V, Cr, and Mn have the azulene units functioning as
      bis(pentahapto) ligands to each metal atom similar to the azulene ligand in the
      long-known molybdenum carbonyl complex (eta(5),eta(5)-C10H8 )Mo2 (CO)6 . The
      metal-metal bonds in these early transition metal structures have distances and
      Wiberg bond indices consistent with the formal bond orders required to give each
      metal atom an 18-electron configuration for the singlet structures and a 17
      electron configuration for the triplet structures. For the later transition
      metals Fe, Co, and Ni, the lowest energy (C10H8)2 M2 structures contain
      pentahapto-trihapto azulene ligands with an uncomplexed C=C double bond, similar
      to that in the long-known iron carbonyl complex (eta(5),eta(3)-C10H8)Fe2 (CO)5 .
      The parallel (eta(5),eta(3)-C10H8 )2M2 (M = Fe, Co, Ni) structures contain
      metallocene subunits with their metal atoms at long nonbonding distances of 3.5
      3.9 A from the other metal atom, which is located between the azulene C7 rings.
      Higher energy opposed (C10H8)2 Fe2 structures contain an unprecedented distorted
      eta(6) ,eta(4) -azulene ligand using six carbon atoms for bonding to one iron
      atom as a hexahapto fulvene ligand and the remaining four carbon atoms for
      bonding to the other iron atom as a tetrahapto diene ligand.

PMID- 26213101
TI  - Molecular identification of the strongyloid nematode Oesophagostomum aculeatum in
      the Asian wild elephant Elephas maximus.
AB  - The transmission of zoonoses by wildlife, including elephants, is a growing
      global concern. In this study, we screened for helminth infections among Asian
      wild elephants (Elephas maximus) of the Salakpra Wildlife Sanctuary,
      Kanchanaburi, Thailand. Elephant faecal samples (45) were collected from the
      sanctuary grounds during January through November 2013 and assayed individually
      using the tetranucleotide microsatellite technique. Microscopic examination
      indicated a high prevalence of strongylids (93.0%) and low prevalences of
      trichurids (2.3%) and ascarids (2.3%). To identify the strongylid species, small
      subunit (SSU) rDNA sequences were amplified from copro-DNA and compared with
      sequences in GenBank. The generated SSU-rDNA sequences comprised five distinct
      haplotypes that were closely related to Oesophagostomum aculeatum. A phylogenetic
      analysis that incorporated related nematodes yielded a tree separated into two
      main clades, one containing our samples and human and domestic animal hookworms
      and the other consisting of Strongyloides. The present results indicate that O.
      aculeatum in local elephants is a potential source of helminthiasis in human and
      domestic animals in this wild-elephant irrupted area. 

PMID- 26213100
TI  - Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects
      against stress-induced cardiomyopathy.
AB  - The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the
      ACP1 gene, is a ubiquitously expressed phosphatase whose in vivo function in the
      heart and in cardiac diseases remains unknown. To investigate the in vivo role of
      LMPTP in cardiac function, we generated mice with genetic inactivation of the
      Acp1 locus and studied their response to long-term pressure overload. Acp1(-/-)
      mice develop normally and ageing mice do not show pathology in major tissues
      under basal conditions. However, Acp1(-/-) mice are strikingly resistant to
      pressure overload hypertrophy and heart failure. Lmptp expression is high in the
      embryonic mouse heart, decreased in the postnatal stage, and increased in the
      adult mouse failing heart. We also show that LMPTP expression increases in end
      stage heart failure in humans. Consistent with their protected phenotype, Acp1(-/
      ) mice subjected to pressure overload hypertrophy have attenuated fibrosis and
      decreased expression of fibrotic genes. Transcriptional profiling and analysis of
      molecular signalling show that the resistance of Acp1(-/-) mice to pathological
      cardiac stress correlates with marginal re-expression of fetal cardiac genes,
      increased insulin receptor beta phosphorylation, as well as PKA and ephrin
      receptor expression, and inactivation of the CaMKIIdelta pathway. Our data show
      that ablation of Lmptp inhibits pathological cardiac remodelling and suggest that
      inhibition of LMPTP may be of therapeutic relevance for the treatment of human
      heart failure.

PMID- 26213102
TI  - Q-RRBS: a quantitative reduced representation bisulfite sequencing method for
      single-cell methylome analyses.
AB  - Reduced representation bisulfite sequencing (RRBS) is a powerful method of DNA
      methylome profiling that can be applied to single cells. However, no previous
      report has described how PCR-based duplication-induced artifacts affect the
      accuracy of this method when measuring DNA methylation levels. For quantifying
      the effects of duplication-induced artifacts on methylome profiling when using
      ultra-trace amounts of starting material, we developed a novel method, namely
      quantitative RRBS (Q-RRBS), in which PCR-induced duplication is excluded through
      the use of unique molecular identifiers (UMIs). By performing Q-RRBS on varying
      amounts of starting material, we determined that duplication-induced artifacts
      were more severe when small quantities of the starting material were used.
      However, through using the UMIs, we successfully eliminated these artifacts. In
      addition, Q-RRBS could accurately detect allele-specific methylation in absence
      of allele-specific genetic variants. Our results demonstrate that Q-RRBS is an
      optimal strategy for DNA methylation profiling of single cells or samples
      containing ultra-trace amounts of cells. 

PMID- 26213103
TI  - Transcutaneous port for levodopa/carbidopa intestinal gel administration in
      Parkinson's disease.
AB  - OBJECTIVE: To evaluate the safety and tolerability of the T-Port((r)) for
      intestinal infusion of levodopa/carbidopa gel in patients with advanced
      Parkinson's disease (PD). METHODS: This prospective study was carried out in 24
      patients with PD (15 males, mean age 61.8 years, mean duration PD 18.7 years).
      All adverse device effects were evaluated at 2 weeks, 3 months and 6 months and
      until explantation or death. RESULTS: Post-operative complications were similar
      to endoscopic gastrojejunostomy placement (four peritoneal irritation, one pocket
      pain). Eight patients with prior experience with the endoscopic gastrojejunostomy
      preferred the T-Port. The total device experience was 83.6 years, and the average
      survival time was 3.6 (range 1.1-5.2) years. Six T-Ports were still in use, and
      two patients had died due to non-device-related reasons. Sixteen T-Ports had been
      explanted due to 15 stoma reactions (14 inflammations and one infection) and one
      tilting of the T-Port. The T-Ports were replaced with endoscopic
      gastrojejunostomy system as replacements with T-Ports were not part of the study.
      Only two device malfunctions occurred (one catheter breakage at 3 year post
      implant and one T-Port leakage of levodopa/carbidopa gel). No tube kinking,
      dislocation or blockage occurred. The number of adverse device effects proved to
      be significantly lower as compared to the endoscopic gastrojejunostomy literature
      data. CONCLUSIONS: The T-Port is safe and well tolerated, and the low number of
      tube problems is a potential advantage compared with the endoscopic
      gastrojejunostomy system. Proper cleaning and local treatment of the stoma site
      around the T-Port are essential to prolong its longevity.

PMID- 26213104
TI  - Adenosine A1( )receptors are selectively coupled to Galpha(i-3) in postmortem
      human brain cortex: Guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS)
      binding/immunoprecipitation study.
AB  - By means of guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding
      assay combined with immunoprecipitation using anti-Galpha subunit antibody, we
      recently reported 5-HT2A receptor- and M1 muscarinic acetylcholine receptor
      mediated Galphaq activation in rat cerebral cortical membranes (Odagaki et al.,
      2014). In the present study, this method has been applied to postmortem human
      brains, with focusing on adenosine receptor-mediated G-protein activation. In the
      exploratory experiments using a series of agonists and the antibodies specific to
      each Galpha subtypes in the presence of low (10 nM) or high (50 MUM)
      concentration of GDP, the most prominent increases in specific [(35)S]GTPgammaS
      binding in the membranes prepared from human prefrontal cortex were obtained for
      the combinations of adenosine (1mM)/anti-Galphai-3 in the presence of 50 MUM GDP
      as well as 5-HT (100 MUM)/anti-Galphaq and carbachol (1mM)/anti-Galphaq in the
      presence of 10nM GDP. Adenosine-induced activation of Galphai-3 emerged only when
      GDP concentrations were increased higher than 10 MUM, and the following
      experiments were performed in the presence of 300 MUM GDP. Adenosine increased
      specific [(35)S]GTPgammaS binding to Galphai-3 in a concentration-dependent
      manner to 251.4% of the basal unstimulated binding, with an EC50 of 1.77 MUM. The
      involvement of adenosine A1 receptor was verified by the experiments using
      selective agonists and antagonists at adenosine A1 or A3 receptor. Among the
      alpha subunits of Gi/o class (Galphai-1, Galphai-2, Galphai-3, and Galphao.),
      only Galphai-3 was activated by 1mM adenosine, indicating that human brain
      adenosine A1 receptor is coupled preferentially, if not exclusively, to Galphai
      3.

PMID- 26213106
TI  - Impact of Total Knee Arthroplasty as Assessed Using Patient-Reported Pain and
      Health-Related Quality of Life Indices: Rheumatoid Arthritis Versus
      Osteoarthritis.
AB  - OBJECTIVE: To assess and compare the impact of total knee arthroplasty (TKA) in
      patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA).
      METHODS: Patients with rheumatologist-diagnosed arthritis undergoing primary TKA
      during 1999-2012 were identified. Indices of pain (overall, index knee, and
      contralateral knee) and health-related quality of life (HRQOL) were obtained in 3
      consecutive 6-month intervals: preoperative (baseline), perioperative, and
      postoperative (recovery). Descriptive statistics and one-way analysis of variance
      were used to compare TKA outcomes by diagnosis. Effect sizes and standardized
      response means (SRMs) were calculated between baseline and recovery. RESULTS: Of
      the participating 18,897 patients, 834 of those with RA (5.3%) and 315 of those
      with OA (10.2%) had undergone index TKA at similar mean ages (65 and 68 years).
      Post-TKA, significant improvements were observed for most domains of pain,
      function, and HRQOL within both disease groups, with greater impact in OA. Based
      on the SRM, the maximum improvement was shown in index knee pain (SRM -1.33 in RA
      and -1.34 in OA; effect size -1.75 and -1.94, respectively). The Health
      Assessment Questionnaire II and the Short Form 36 physical component summary were
      the most responsive HRQOL indices in detecting post-TKA improvement in RA. A
      diagnosis of RA, lower income, and preoperative anxiety were independently
      associated with a lower degree of improvement in index knee pain following TKA.
      CONCLUSION: TKA is highly effective in reducing clinically relevant knee pain (to
      a greater extent than its effect on other subjective HRQOL indices in patients
      with RA), although this improvement is less marked as compared to that among
      patients with OA. TKA serves as a "time machine" via which patients can return to
      a lifestyle with less disability, before the arthritis process catches up in RA.

PMID- 26213105
TI  - The association between intelligence and lifespan is mostly genetic.
AB  - BACKGROUND: Several studies in the new field of cognitive epidemiology have shown
      that higher intelligence predicts longer lifespan. This positive correlation
      might arise from socioeconomic status influencing both intelligence and health;
      intelligence leading to better health behaviours; and/or some shared genetic
      factors influencing both intelligence and health. Distinguishing among these
      hypotheses is crucial for medicine and public health, but can only be
      accomplished by studying a genetically informative sample. METHODS: We analysed
      data from three genetically informative samples containing information on
      intelligence and mortality: Sample 1, 377 pairs of male veterans from the NAS-NRC
      US World War II Twin Registry; Sample 2, 246 pairs of twins from the Swedish Twin
      Registry; and Sample 3, 784 pairs of twins from the Danish Twin Registry. The age
      at which intelligence was measured differed between the samples. We used three
      methods of genetic analysis to examine the relationship between intelligence and
      lifespan: we calculated the proportion of the more intelligent twins who outlived
      their co-twin; we regressed within-twin-pair lifespan differences on within-twin
      pair intelligence differences; and we used the resulting regression coefficients
      to model the additive genetic covariance. We conducted a meta-analysis of the
      regression coefficients across the three samples. RESULTS: The combined (and all
      three individual samples) showed a small positive phenotypic correlation between
      intelligence and lifespan. In the combined sample observed r = .12 (95%
      confidence interval .06 to .18). The additive genetic covariance model supported
      a genetic relationship between intelligence and lifespan. In the combined sample
      the genetic contribution to the covariance was 95%; in the US study, 84%; in the
      Swedish study, 86%, and in the Danish study, 85%. CONCLUSIONS: The finding of
      common genetic effects between lifespan and intelligence has important
      implications for public health, and for those interested in the genetics of
      intelligence, lifespan or inequalities in health outcomes including lifespan.

PMID- 26213107
TI  - CD70: An emerging target in cancer immunotherapy.
AB  - Over the last decades, advances in the knowledge of immunology have led to the
      identification of immune checkpoints, reinvigorating cancer immunotherapy.
      Although normally restricted to activated T and B cells, constitutive expression
      of CD70 in tumor cells has been described. Moreover, CD70 is implicated in tumor
      cell and regulatory T cell survival through interaction with its ligand, CD27. In
      this review, we summarize the targetable expression patterns of CD70 in a wide
      range of malignancies and the promising mechanism of anti-CD70 therapy in
      stimulating the anti-tumor immune response. In addition, we will discuss clinical
      data and future combination strategies. 

PMID- 26213108
TI  - Changes in mu-opioid receptor expression and function in the mesolimbic system
      after long-term access to a palatable diet.
AB  - The incidence of obesity in both adults and children is rising. In order to
      develop effective treatments for obesity, it is important to understand how diet
      can induce changes in the brain that could promote excessive intake of high
      calorie foods and alter the efficacy of therapeutic targets. The mu-opioid
      receptor is involved in regulating the motivation for and hedonic reaction to
      food. Here, we review the literature examining changes in the expression and
      function of mu-opioid receptors in the mesolimbic system of rodents after
      extended access to a high-fat diet. We also review how maternal diet can induce
      long-term changes in the expression or function of mu-opioid receptors in the
      mesolimbic system of offspring. Understanding the behavioural and therapeutic
      implications of these changes requires further study. 

PMID- 26213109
TI  - Pharmacological treatment of aldosterone excess.
AB  - Primary aldosteronism, caused by autonomous secretion of aldosterone by the
      adrenals, is estimated to account for at least 5% of hypertension cases.
      Hypertension explains the considerable cardiovascular morbidity caused by
      aldosteronism only partly, calling for specific anti-aldosterone drugs. The
      pharmacology of aldosterone is complex due to high homology with other steroids,
      the resemblance of steroid receptors, and the common pathways of steroid
      synthesis. Classically, pharmacological treatment of aldosteronism relied on the
      mineralocorticoid receptor (MR) antagonist spironolactone, which is highly
      effective, but causes considerable, mainly sexual side-effects due to limited
      selectivity for the MR. New agents have been developed or are being developed
      that aim at higher selectivity for MR antagonists (eplerenone, dihydropyridine
      derived calcium channel blockers (CCB)), or inhibition of aldosterone synthesis.
      Eplerenone is less potent than spironolactone, but causes fewer adverse effects
      due to its selectivity for the MR. Non-steroidal MR antagonists have been
      developed from dihydropyridine CCBs, having lost their CCB activity and being
      highly selective for the MR. The first clinical studies with these drugs are
      underway. Aldosterone synthase inhibitors are an attractive alternative, but are
      prone to interference with cortisol synthesis due to the inhibition of 11-beta
      hydroxylation, an essential step in both cortisol and aldosterone synthesis, and
      accumulation of mineralocorticoid precursors. In coming years clinical research
      will provide the answers as to which drugs and strategies to treat high
      aldosterone states are the most effective. 

PMID- 26213110
TI  - The first WFSBP Consensus Report for Biomarkers of Schizophrenia part I:
      Neurophysiology, as well as original investigations with a focus on physiological
      components of emotional states and affective disorders.

PMID- 26213111
TI  - Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for
      biomarkers and endophenotypes of schizophrenia part I: Neurophysiology.
AB  - The neurophysiological components that have been proposed as biomarkers or as
      endophenotypes for schizophrenia can be measured through electroencephalography
      (EEG) and magnetoencephalography (MEG), transcranial magnetic stimulation (TMS),
      polysomnography (PSG), registration of event-related potentials (ERPs),
      assessment of smooth pursuit eye movements (SPEM) and antisaccade paradigms. Most
      of them demonstrate deficits in schizophrenia, show at least moderate stability
      over time and do not depend on clinical status, which means that they fulfil the
      criteria as valid endophenotypes for genetic studies. Deficits in cortical
      inhibition and plasticity measured using non-invasive brain stimulation
      techniques seem promising markers of outcome and prognosis. However the utility
      of these markers as biomarkers for predicting conversion to psychosis, response
      to treatments, or for tracking disease progression needs to be further studied. 

PMID- 26213112
TI  - How and when plume zonation appeared during the 132 Myr evolution of the Tristan
      Hotspot.
AB  - Increasingly, spatial geochemical zonation, present as geographically distinct,
      subparallel trends, is observed along hotspot tracks, such as Hawaii and the
      Galapagos. The origin of this zonation is currently unclear. Recently zonation
      was found along the last ~70 Myr of the Tristan-Gough hotspot track. Here we
      present new Sr-Nd-Pb-Hf isotope data from the older parts of this hotspot track
      (Walvis Ridge and Rio Grande Rise) and re-evaluate published data from the
      Etendeka and Parana flood basalts erupted at the initiation of the hotspot track.
      We show that only the enriched Gough, but not the less-enriched Tristan,
      component is present in the earlier (70-132 Ma) history of the hotspot. Here we
      present a model that can explain the temporal evolution and origin of plume
      zonation for both the Tristan-Gough and Hawaiian hotspots, two end member types
      of zoned plumes, through processes taking place in the plume sources at the base
      of the lower mantle. 

PMID- 26213113
TI  - Clinical manifestations of neuromyelitis optica in male and female patients.
AB  - Neuromyelitis optica (NMO) is a severe, idiopathic, immuno-mediated, inflammatory
      demyelinating disease of the central nervous system. We examined the clinical
      features between male and female NMO patients, for which not much data exist. One
      hundred and eight Chinese Han patients with NMO were analysed retrospectively,
      all had been detected for the aquaporin-4 (AQP4) antibody using a cell-based
      assay. Of 108 NMO patients, 92 were female and 16 were male (female/male = 5.75).
      Ninety-four (87%) were positive for the AQP4 antibody in their serum and/or
      cerebral spinal fluid. Aquaporin-4 antibody-positive NMO patients had a higher
      female/male ratio than the negative group (P = 0.001). Female NMO patients had a
      higher positive rate of the AQP4 antibody than male NMO patients (92.4 vs 56.3%,
      P = 0.001). All NMO male patients were divided according to their AQP4 antibody
      status. 77.8% (7/9) of patients in the seropositive group had initial optic
      neuritis, while only one patient (14.3%, 1/7) in the negative group had optic
      neuritis (P = 0.041). Limb paraesthesia was reported in only one patient in the
      negative group (11.1%), but it was reported in all patients in the positive group
      (100%) (P = 0.001). The mean length of vertebral segments of the spinal cord
      lesions was 3.6 +/- 1.3 in the positive group, while it was 6.6 +/- 2.6 in the
      negative group (P < 0.0001). The involvement of the cervical spinal cord was
      found in 88.9% (8/9) of the positive members, but only 11.1% in the negative
      group (P = 0.009). However, the involvement of the thoracic spinal cord was found
      in 22.2% of patients in the positive group and 85.7% of patients in the negative
      members (P = 0.041). In conclusion, male NMO is rare and has a low positive rate
      of AQP4 antibody. 

PMID- 26213114
TI  - Metal Microporous Aromatic Polymers with Improved Performance for Small Gas
      Storage.
AB  - A novel metal-doping strategy was developed for the construction of iron
      decorated microporous aromatic polymers with high small-gas-uptake capacities.
      Cost-effective ferrocene-functionalized microporous aromatic polymers (FMAPs)
      were constructed by a one-step Friedel-Crafts reaction of ferrocene and s
      triazine monomers. The introduction of ferrocene endows the microporous polymers
      with a regular and homogenous dispersion of iron, which avoids the slow reunion
      that is usually encountered in previously reported metal-doping procedures,
      permitting a strong interaction between the porous solid and guest gases.
      Compared to ferrocene-free analogues, FMAP-1, which has a moderate BET surface
      area, shows good gas-adsorption capabilities for H2 (1.75 wt % at 77 K/1.0 bar),
      CH4 (5.5 wt % at 298 K/25.0 bar), and CO2 (16.9 wt % at 273 K/1.0 bar), as well
      as a remarkably high ideal adsorbed solution theory CO2 /N2 selectivity (107 v/v
      at 273 K/(0-1.0) bar), and high isosteric heats of adsorption of H2 (16.9 kJ mol(
      1) ) and CO2 (41.6 kJ mol(-1) ). 

PMID- 26213115
TI  - An in silico platform for predicting, screening and designing of antihypertensive
      peptides.
AB  - High blood pressure or hypertension is an affliction that threatens millions of
      lives worldwide. Peptides from natural origin have been shown recently to be
      highly effective in lowering blood pressure. In the present study, we have framed
      a platform for predicting and designing novel antihypertensive peptides. Due to a
      large variation found in the length of antihypertensive peptides, we divided
      these peptides into four categories (i) Tiny peptides, (ii) small peptides, (iii)
      medium peptides and (iv) large peptides. First, we developed SVM based regression
      models for tiny peptides using chemical descriptors and achieved maximum
      correlation of 0.701 and 0.543 for dipeptides and tripeptides, respectively.
      Second, classification models were developed for small peptides and achieved
      maximum accuracy of 76.67%, 72.04% and 77.39% for tetrapeptide, pentapeptide and
      hexapeptides, respectively. Third, we have developed a model for medium peptides
      using amino acid composition and achieved maximum accuracy of 82.61%. Finally, we
      have developed a model for large peptides using amino acid composition and
      achieved maximum accuracy of 84.21%. Based on the above study, a web-based
      platform has been developed for locating antihypertensive peptides in a protein,
      screening of peptides and designing of antihypertensive peptides. 

PMID- 26213116
TI  - Serial determinations of asymmetric dimethylarginine and homocysteine during
      pregnancy to predict pre-eclampsia: a longitudinal study.
AB  - OBJECTIVE: To evaluate the usefulness of serial determinations of asymmetric
      dimethylarginine (ADMA) and homocysteine (Hcy) concentrations during pregnancy to
      predict pre-eclampsia, taking into account maternal obesity and B vitamin status.
      DESIGN: Longitudinal study. SETTING: Two obstetric referral hospitals. SAMPLE:
      Two hundred and fifty-two of 411 women invited to participate in the study.
      METHODS: The women made monthly visits from <=20 weeks of gestation until
      delivery for measurements of plasma ADMA, Hcy, and vitamins B6 , B12, and folic
      acid, and for the recording of clinical information. MAIN OUTCOME MEASURE: Early
      elevations in plasma ADMA and Hcy related to the development of pre-eclampsia.
      RESULTS: Of the 252 women who completed the study, 179 had no complications, 49
      developed pre-eclampsia, and 24 presented with complications other than pre
      eclampsia. ADMA and Hcy increased gradually throughout pregnancy in the pre
      eclampsia group, independent of maternal B-vitamin status and obesity, but
      remained constant in women with no complications. Relative to the preceding
      month, ADMA and Hcy levels increased 1 month prior to the onset of pre-eclampsia:
      124 +/- 27 nmol (P < 0.001) and 1177 +/- 278 nmol (P = 0.001), respectively, in
      the pre-eclampsia group. The group of women with no complications did not show
      any significant changes. Increases of 80 nmol ADMA and 1000 nmol Hcy at 1 month
      prior to the onset of pre-eclampsia demonstrated the best potential for
      prediction. CONCLUSIONS: Increased ADMA and Hcy levels precede clinical
      manifestations of pre-eclampsia. Therefore, serial determinations of their
      concentrations may be helpful in identifying women at risk. TWEETABLE ABSTRACT:
      Increased ADMA and Hcy precede clinical pre-eclampsia and may identify women at
      risk.

PMID- 26213117
TI  - Repetitive acute intermittent hypoxia does not promote generalized inflammatory
      gene expression in the rat CNS.
AB  - Modest protocols of repetitive acute intermittent hypoxia (rAIH) enhance motor
      function in patients with chronic incomplete spinal injury. Since chronic
      intermittent hypoxia (CIH) elicits neuroinflammation, there is potential for rAIH
      to have similar effects. Thus, we tested the hypothesis that rAIH has minimal
      impact on microglial inflammatory gene expression, but up-regulates key
      neurotrophic factor expression in a CNS region-specific manner. Using real time
      PCR, we evaluated mRNA levels of inflammatory and neurotrophic factors in
      immunomagnetically-isolated microglia from rat frontal cortex, brainstem and
      upper and lower cervical spinal cord following rAIH (ten, 5-min episodes, thrice
      weekly, 4 weeks). In agreement with our hypothesis, rAIH had no significant
      impact on microglial inflammatory gene expression in any region studied. On the
      other hand, neurotrophic factor expression was altered in a gene- and region
      specific pattern. These results have important implications for the safety of
      rAIH as a potential therapy to enhance neuroplasticity and motor function in
      patients with spinal injury or other neurologic disorders. 

PMID- 26213118
TI  - Mechanical consequences of allergic induced remodeling on mice airway resistance
      and compressibility.
AB  - The effect of remodeling on airway function is uncertain. It may affect airway
      compressibility during forced expirations differently than airflow resistance,
      providing a tool for its assessment. The aim of the current study was to compare
      the effects of acute and chronic antigen challenge on methacholine-induced
      bronchoconstriction assessed from resistance and maximal tidal expiratory flow.
      Balb/C mice were sensitized with ovalbumin (OVA) and challenged either daily for
      three days with intra-nasal OVA or daily for 5 days and three times a week for 5
      subsequent weeks. Acute and chronic allergen challenge induced airway
      hyperresponsiveness (AHR) to methacholine. However the relationship between
      maximal tidal expiratory flow and resistance during methacholine challenge was
      different between the two conditions, suggesting that the determinants of AHR are
      not identical following acute and chronic allergen exposure. We conclude that the
      contrast of changes in maximal tidal expiratory flow and respiratory resistance
      during methacholine-induced bronchoconstriction may allow the detection of the
      mechanical consequences of airway remodeling. 

PMID- 26213122
TI  - Free energy minimization and information gain: The devil is in the details.
AB  - Contrary to Friston's previous work, this paper describes free energy
      minimization using categorical probability distributions over discrete states.
      This alternative mathematical framework exposes a fundamental, yet unnoticed
      challenge for the free energy principle. When considering discrete state spaces
      one must specify their granularity, as the amount of information gain is defined
      over this state space. The more detailed this state space, the lower the
      precision of the predictions will be, and consequently, the higher the prediction
      errors. Hence, an optimal trade-off between precision and detail is needed, and
      we call for incorporating this aspect in the free energy principle. 

PMID- 26213119
TI  - OsPIN5b modulates rice (Oryza sativa) plant architecture and yield by changing
      auxin homeostasis, transport and distribution.
AB  - Plant architecture attributes such as tillering, plant height and panicle size
      are important agronomic traits that determine rice (Oryza sativa) productivity.
      Here, we report that altered auxin content, transport and distribution affect
      these traits, and hence rice yield. Overexpression of the auxin efflux carrier
      like gene OsPIN5b causes pleiotropic effects, mainly reducing plant height, leaf
      and tiller number, shoot and root biomass, seed-setting rate, panicle length and
      yield parameters. Conversely, reduced expression of OsPIN5b results in higher
      tiller number, more vigorous root system, longer panicles and increased yield. We
      show that OsPIN5b is an endoplasmic reticulum (ER) -localized protein that
      participates in auxin homeostasis, transport and distribution in vivo. This work
      describes an example of an auxin-related gene where modulating its expression can
      simultaneously improve plant architecture and yield potential in rice, and
      reveals an important effect of hormonal signaling on these traits. 

PMID- 26213123
TI  - Electron-Phonon Coupling in CdSe/CdS Core/Shell Quantum Dots.
AB  - Resonance Raman spectra and excitation profiles have been measured and
      semiquantitatively modeled for core/shell quantum dots consisting of 2.7 nm
      diameter zincblende CdSe cores and thin (0.5 nm) or thick (1.6 nm) CdS shells.
      The Raman spectra show previously reported trends of increased peak frequency for
      both the CdSe and the CdS longitudinal optical (LO) phonons with increasing shell
      thickness. We also find a strong dependence of the peak CdS frequency on
      excitation energy and a large discrepancy between the experimental frequency of
      the CdSe + CdS combination band and the sum of the corresponding fundamental
      frequencies. This suggests that the dominant transitions at high excitation
      energies are localized on either the CdSe core or the CdS shell and thereby
      cannot enhance combination band transitions between core and shell. The CdS to
      CdSe Raman intensity ratios at high excitation energies further support this
      picture. The electron-phonon coupling for the CdSe LO phonon in the lowest
      excitonic transition is slightly weaker in the core/shell structures than in pure
      CdSe quantum dots, contrary to expectations for the Frohlich coupling mechanism.
      Possible explanations for this discrepancy are discussed. 

PMID- 26213124
TI  - Emotion impairs extrinsic source memory--An ERP study.
AB  - Substantial advancements in understanding emotional modulation of item memory
      notwithstanding, controversies remain as to how emotion influences source memory.
      Using an emotional extrinsic source memory paradigm combined with remember/know
      judgments and two key event-related potentials (ERPs)-the FN400 (a frontal
      potential at 300-500 ms related to familiarity) and the LPC (a later parietal
      potential at 500-700 ms related to recollection), our research investigated the
      impact of emotion on extrinsic source memory and the underlying processes. We
      varied a semantic prompt (either "people" or "scene") preceding a study item to
      manipulate the extrinsic source. Behavioral data indicated a significant effect
      of emotion on "remember" responses to extrinsic source details, suggesting
      impaired recollection-based source memory in emotional (both positive and
      negative) relative to neutral conditions. In parallel, differential FN400 and LPC
      amplitudes (correctly remembered - incorrectly remembered sources) revealed
      emotion-related interference, suggesting impaired familiarity and recollection
      memory of extrinsic sources associated with positive or negative items. These
      findings thus lend support to the notion of emotion-induced memory trade off:
      while enhancing memory of central items and intrinsic/integral source details,
      emotion nevertheless disrupts memory of peripheral contextual details,
      potentially impairing both familiarity and recollection. Importantly, that
      positive and negative items result in comparable memory impairment suggests that
      arousal (vs. affective valence) plays a critical role in modulating dynamic
      interactions among automatic and elaborate processes involved in memory.

PMID- 26213125
TI  - Greater aerobic fitness is associated with more efficient inhibition of task
      irrelevant information in preadolescent children.
AB  - A growing number of neuroelectric studies using event-related brain potentials
      have demonstrated that greater aerobic fitness is associated with superior
      cognitive functioning across the lifespan. However, empirical data regarding the
      association between fitness and attentional orienting is scarce, with no evidence
      in children, and the findings are inconclusive. We designed the present study to
      examine the relationship between aerobic fitness and involuntary attentional
      orientation to task-irrelevant information in preadolescent children. Lower-fit
      and higher-fit children performed a visual oddball task in which irregular (i.e.,
      rule-violating) stimuli appeared as a task-irrelevant dimension, while measures
      of task performance and the P3a component elicited by the irregular stimuli were
      assessed. Analyses revealed that higher-fit children exhibited lower miss rates
      and smaller P3a amplitude relative to lower-fit children. These findings suggest
      that greater childhood fitness is associated with more efficient inhibition of
      task-irrelevant information. 

PMID- 26213127
TI  - Parity and litter size effects on maternal behavior of Small Tail Han sheep in
      China.
AB  - The effects of parity and litter size on maternal behavior of Small Tail Han
      sheep was investigated at Linyi University, China. Sixty-eight ewes were observed
      from parturition to weaning. Continuous focal animal sampling was used to
      quantify the duration of maternal behaviors. Ewe feces were collected every 2
      days and estradiol concentration was measured with an enzyme immunoassay kit. All
      lambs were weighed 24 h after parturition and again at 35 days of age. Parity
      increased sucking, following, grooming, low-pitched bleat, head-up and udder
      refusal behavior and decreased aggressive behavior (P < 0.01, P < 0.01, P < 0.05,
      P < 0.05, P < 0.05, P < 0.05, P < 0.01, respectively), and litter size showed
      significant effect on sucking, following and low-pitched bleat behavior (P <
      0.05, P < 0.01, P < 0.05, respectively). The lambs of multiparous ewes were
      significantly heavier than primiparous ewes at birth (P < 0.01) and were
      significantly heavier at weaning age (P < 0.01). Similar results were founded for
      birth weight and weaning weight gain in litter size (P < 0.01, P < 0.01,
      respectively). Estradiol concentration in feces was higher in multiparous ewes
      than primiparous ewes. Parity and litter size may have effects on maternal
      behavior during lactation. Ewes that have 2-3 lambs may be more suitable for
      production of Small Tail Han sheep in China. 

PMID- 26213126
TI  - Von Willebrand factor-A1 domain binds platelet glycoprotein Ibalpha in multiple
      states with distinctive force-dependent dissociation kinetics.
AB  - Circulating von Willebrand factor (VWF) adopts a closed conformation that shields
      the platelet glycoprotein Ibalpha (GPIbalpha) binding site in the VWF-A1 domain.
      Immobilized at sites of vascular injury, VWF is activated by its interaction with
      collagen and the exertion of increased hemodynamic forces. Studies on native VWF
      strings and isolated A1 domains suggest the existence of multiple A1 binding
      states in different biophysical contexts. In this single-molecule study, we have
      used a biomembrane force probe (BFP) and a flow chamber to identify and
      characterize a collagen binding induced conformation with a higher affinity to
      platelet GPIbalpha. As force increases, our results show that collagen binding
      increases the stability of GPIbalpha bond with both VWF and isolated A1 domain.
      However, the collagen 2D binding affinity for VWF-A3 domain is 10 times of that
      for A1 domain, suggesting the initial VWF capture is mediated by A3-collagen
      interaction while A1-collagen regulates the subsequent VWF activation. Our
      results reveal the molecular mechanism of collagen-regulated, A1-mediated
      platelet adhesion enhancement. Characterization of different A1 states provides
      insights into binding heterogeneity of VWF in different scenarios of inflammation
      and thrombosis. 

PMID- 26213130
TI  - Development of a smartphone application for eating disorder self-monitoring.
AB  - OBJECTIVE: This case report aims to (1) describe the development and refinement
      of a smartphone application for eating disorder self-monitoring; (2) characterize
      its users in terms of demographic and clinical characteristics; and (3) explore
      its feasibility and utilization as a self-monitoring tool. METHOD: We developed a
      mobile phone application through which people with eating disorders can self
      monitor meals, emotions, behaviors, and thoughts. The application also included
      positive reinforcement, coping skill suggestions, social support, and feedback
      components. The app was made available on two Internet app stores. Data include
      number of downloads and subsequent usage statistics, consumer ratings on app
      stores are used as indicators of satisfaction, anonymous aggregate demographic
      data and Eating Disorder Examination Questionnaire scores from 57,940 individuals
      collected over a two-year period. RESULTS: The app demonstrated population-level
      utilization with over 100,000 users over a two-year period. Almost 50% percent of
      users stated that they are not currently receiving clinical treatment and 33%
      reported they had not told anyone about their eating disorder. A surprising
      number of people with severe problems are using the app. DISCUSSION: Smartphone
      apps have the capacity to reach and engage traditionally underserved individuals
      with eating disorders at a large scale. Additional work is indicated for the
      evaluation of the clinical effectiveness of applications for specific user groups
      and in clinical treatment contexts.

PMID- 26213131
TI  - Enhanced rice production but greatly reduced carbon emission following biochar
      amendment in a metal-polluted rice paddy.
AB  - Soil amendment of biochar (BSA) had been shown effective for mitigating
      greenhouse gas (GHG) emission and alleviating metal stress to plants and microbes
      in soil. It has not yet been addressed if biochar exerts synergy effects on crop
      production, GHG emission, and microbial activity in metal-polluted soils. In a
      field experiment, biochar was amended at sequential rates at 0, 10, 20, and 40 t
      ha(-1), respectively, in a cadmium- and lead-contaminated rice paddy from the Tai
      lake Plain, China, before rice cropping in 2010. Fluxes of soil carbon dioxide
      (CO2), methane (CH4), and nitrous oxide (N2O) were monitored using a static
      chamber method during the whole rice growing season (WRGS) of 2011. BSA
      significantly reduced soil CaCl2 extractable pool of Cd, and DTPA extractable
      pool of Cd and Pb. As compared to control, soil CO2 emission under BSA was
      observed to have no change at 10 t ha(-1) but decreased by 16-24% at 20 and 40 t
      ha(-1). In a similar trend, BSA at 20 and 40 t ha(-1) increased rice yield by 25
      26% and thus enhanced ecosystem CO2 sequestration by 47-55% over the control.
      Seasonal total N2O emission was reduced by 7.1, 30.7, and 48.6% under BSA at 10,
      20, and 40 t ha(-1), respectively. Overall, a net reduction in greenhouse gas
      balance (NGHGB) by 53.9-62.8% and in greenhouse gas intensity (GHGI) by 14.3
      28.6% was observed following BSA at 20 and 40 t ha(-1). The present study
      suggested a great potential of biochar to enhancing grain yield while reducing
      carbon emission in metal-polluted rice paddies.

PMID- 26213133
TI  - Removal of cyanobacteria from synthetic and real water by dielectric barrier
      discharge process.
AB  - The feasibility of cyanobacteria removal from freshwater by a dielectric barrier
      discharge (DBD) process is investigated. Seven commercial and environmental
      cyanobacteria strains, as well as real algae-laden water, were tested. The
      removal of the cyanobacteria was evaluated by analyzing the changes in
      chlorophyll a content, total organic carbon (TOC) concentration, and cell
      morphology. Nearly total removal of chlorophyll a was achieved within 20 min,
      while the TOC analysis exhibited an increase-decrease-increase trend in 60 min of
      treatment, likely due to the oxidation of intracellular and intercellular
      materials. Observation under light microscopy revealed the disruption of
      intracellular and intercellular structures within 5 min of DBD treatment and thus
      supported the TOC analysis. Increasing the salinity of the medium from 0 to 5
      parts per thousand (ppt) improved treatment efficiency, where similar level of
      chlorophyll a removal (around 93%) was achieved in only half the treatment time.
      Application of DBD on real algae-laden water from a fish farm yielded higher
      treatment efficiency than in synthetic medium, indicating the promising
      application of DBD as a means to control cyanobacteria bloom in fresh and estuary
      water bodies.

PMID- 26213132
TI  - Integron diversity in marine environments.
AB  - Integrons are bacterial genetic elements known to be active vectors of antibiotic
      resistance among clinical bacteria. They are also found in bacterial communities
      from natural environments. Although integrons have become especially efficient
      for bacterial adaptation in the particular context of antibiotic usage, their
      role in natural environments in other contexts is still unknown. Indeed, most
      studies have focused on integrons and the spread of antibiotic resistance in
      freshwater or soil impacted by anthropogenic activities, with only few on marine
      environments. Notably, integrons show a wider diversity of both gene cassettes
      and integrase gene in natural environments than in clinical environments,
      suggesting a general role of integrons in bacterial adaptation. This article
      reviews the current knowledge on integrons in marine environments. We also
      present conclusions of our studies on polluted and nonpolluted backgrounds.

PMID- 26213134
TI  - Residential heating contribution to level of air pollutants (PAHs, major, trace,
      and rare earth elements): a moss bag case study.
AB  - In areas with moderate to continental climates, emissions from residential
      heating system lead to the winter air pollution peaks. The EU legislation
      requires only the monitoring of airborne concentrations of particulate matter,
      As, Cd, Hg, Ni, and B[a]P. Transition metals and rare earth elements (REEs) have
      also arisen questions about their detrimental health effects. In that sense, this
      study examined the level of extensive set of air pollutants: 16 polycyclic
      aromatic hydrocarbons (PAHs), and 41 major elements, trace elements, and REEs
      using Sphagnum girgensohnii moss bag technique. During the winter of 2013/2014,
      the moss bags were exposed across Belgrade (Serbia) to study the influence of
      residential heating system to the overall air quality. The study was set as an
      extension to our previous survey during the summer, i.e., non-heating season.
      Markedly higher concentrations of all PAHs, Sb, Cu, V, Ni, and Zn were observed
      in the exposed moss in comparison to the initial values. The patterns of the moss
      REE concentrations normalized to North American Shale Composite and Post-Archean
      Australian Shales were identical across the study area but enhanced by
      anthropogenic activities. The results clearly demonstrate the seasonal variations
      in the moss enrichment of the air pollutants. Moreover, the results point out a
      need for monitoring of air quality during the whole year, and also of various
      pollutants, not only those regulated by the EU Directive. 

PMID- 26213135
TI  - Dose-response effect of ergocalciferol therapy on serum 25-hydroxyvitamin D
      concentration during critical illness.
AB  - OBJECTIVE: The aim of this study was to evaluate the dose-response relationship
      between ergocalciferol therapy and serum 25-hydroxyvitamin D concentrations in
      enterally fed, critically ill patients with traumatic injuries. METHODS: A
      retrospective cohort of critically ill patients with traumatic injuries and
      vitamin D deficiency (25-OH vitamin D <50 nmol/L) were given either 50 000 IU of
      liquid ergocalciferol weekly, twice weekly, or three times weekly while in the
      intensive care unit (ICU). Serum 25-OH vitamin D and ionized calcium
      concentrations were monitored weekly. Ergocalciferol therapy was stopped when the
      serum 25-OH vitamin D was >75 nmol/L, if the patient experienced hypercalcemia
      (ionized calcium >1.34 mmol/L), when the patient was discharged from the ICU, or
      if enteral nutrition was discontinued. RESULTS: Sixty-five patients (16, 18, and
      31 per dosage group) were examined. One (6%), two (11%), and eight (26%) patients
      achieved normal 25-OH vitamin D concentrations after 2 to 4 wk of ergocalciferol
      therapy for each dosage group, respectively (P < 0.001). Serum 25-OH vitamin D
      concentrations improved from 36 +/- 6, 40 +/- 7, and 37 +/- 6 nmol/L to 50 +/-
      15, 54 +/- 21, and 62 +/- 17 nmol/L, respectively, after 2 wk of ergocalciferol
      therapy (P < 0.001) Two (13%), one (6%), and seven (23%) patients developed
      hypercalcemia for each dosage group, respectively (P = NS). CONCLUSIONS:
      Ergocalciferol therapy improved baseline serum 25-OH vitamin D concentrations but
      was inadequate for consistently achieving normal serum concentrations of 25-OH
      vitamin D during critical illness. The trend in increasing appearance of mild
      hypercalcemia for the highest dosage group is concerning.

PMID- 26213136
TI  - Learning decision making through serious games.
AB  - BACKGROUND: In Serious Games (SGs), educational content is integrated into a game
      so that learning is intrinsic to play, thereby motivating players and improving
      engagement. SGs enable learning by developing situated understanding in users and
      by enabling players to practise safe clinical decision making; however, the use
      of SGs in medical education is not well established. AIMS: We aimed to design a
      game-based resource to teach clinical decision making to medical students, and to
      assess user perceptions of educational value, usability and the role for SGs in
      undergraduate training. METHODS: An SG focusing on the acute management of
      tachyarrhythmias was developed. Third- and fourth-year medical students at the
      medical school were invited to use and evaluate the game using questionnaires and
      focus groups. RESULTS: We invited 479 students, and 281 accessed the game. Only
      47 students completed the questionnaire and 31 students participated in the focus
      groups. The data suggest that SGs: (1) can allow students to rehearse taking
      responsibility for decision making; (2) are fun and motivational; (3) have a role
      in revising and consolidating knowledge; and (4) could be formative assessment
      tools. Serious Games enable learning by developing situated understanding in
      users CONCLUSIONS: SGs could be employed as adjuvant learning resources to
      develop students' skills and knowledge. Further empirical research is required to
      assess the added value of games in medical education.

PMID- 26213137
TI  - Barriers in using cardiometabolic risk information among consumers with low
      health literacy.
AB  - OBJECTIVES: To identify the barriers from the perspective of consumers with low
      health literacy in using risk information as provided in cardiometabolic risk
      assessments. DESIGN: A qualitative thematic approach using cognitive interviews
      was employed. METHODS: We performed interviews with 23 people with low health
      literacy/health numeracy, who were recruited through (1) several organisations
      and snowball sampling and (2) an online access panel. Participants completed the
      risk test of the Dutch national cardiometabolic risk assessment and viewed the
      personalized information about their risk. They were asked to answer probing
      questions about different parts of the information. The qualitative data were
      analysed by identifying main themes related to barriers in using the information,
      using a descriptive thematic approach. RESULTS: The four main themes identified
      were as follows: (1) People did not fully accept the risk message, partly because
      numerical information had ambiguous meaning; (2) people lacked an adequate
      framework for understanding their risk; (3) the purpose and setting of the risk
      assessment was unclear; and (4) current information tells nothing new: A need for
      more specific risk information. CONCLUSIONS: The main barriers were that the
      current presentation seemed to provoke undervaluation of the risk number and that
      texts throughout the test, for example about cardiometabolic diseases, did not
      match people's existing knowledge, failing to provide an adequate framework for
      understanding cardiometabolic risk. Our findings have implications for the design
      of disease risk information, for example that alternative forms of communication
      should be explored that provide more intuitive meaning of the risk in terms of
      good versus bad. STATEMENT OF CONTRIBUTION: What is already known on this
      subject? Online disease risk assessments have become widely available
      internationally. People with low SES and health literacy tend to participate less
      in health screening. Risk information is difficult to understand, yet little
      research has been carried out among people with low health literacy. What does
      this study add? People with low health literacy do not optimally use risk
      information in an online cardiometabolic risk assessment. The texts provided in
      the cardiometabolic risk assessment do not suit to their existing knowledge. The
      typical risk communication (numbers, bar graph, verbal label) seems to provoke
      undervaluation of risk.

PMID- 26213138
TI  - Prostate cancer as a chronic disease: cost-effectiveness and proper follow-up.
AB  - In western countries, prostate cancer (PCa) is the most common non-dermatological
      malignant disease in men. Bone metastases more often develop in patients with
      advanced PCa; the associated complications present a substantial disease and
      economic burden. Although the introduction of new therapeutic strategies have
      provided some advantages in terms of overall survival and quality of life in
      patients with metastatic PCa, the skeletal related events and side effects due to
      the therapies are associated with an important impact on the healthcare costs. In
      particular, the number of hospital admission, clinical consultation and the
      introduction of new expensive diagnostic modalities have changed the management
      of metastatic patients. However, the National and International guidelines
      suggest to follow patients with metastatic PCa by using clinical assessment,
      biochemical evaluation and, when necessary, diagnostic imaging. The aims of the
      present review were: 1) to summarize the information regarding the clinical and
      economic burden of metastasis; 2) to evaluate the quality of life; and 3) to
      suggest a proper follow-up in advanced PCa patients. 

PMID- 26213139
TI  - Early detection of prostate cancer relapse by biochemistry and diagnostic
      imaging.
AB  - Prostate cancer (PCa) is a common malignancy in men associated with an increase
      in the incidence rate. Radical prostatectomy (RP) or external beam radiotherapy
      (EBRT) represents the most employed treatments for the local control of disease.
      However, 10-50% of patients who experienced a recurrence of disease after primary
      treatments can benefit from salvage or palliative therapies. To date, prostate
      specific antigen (PSA) is usually used in clinical practice to monitor the status
      of disease and to early detect the recurrence of PCa. Nevertheless, PSA cannot
      discriminate the presence of local vs. distant metastatic disease. Circulating
      tumor cells are considered as a sign of disease widespread, but their correlation
      with metastatic PCa and local recurrence of disease is still indeterminate.
      Digital rectal exploration and transrectal ultrasonography are considered the
      first clinical and diagnostic approach to identify the local recurrence of PCa,
      but are associated with a low detection rate and low diagnostic accuracies.
      Conversely, magnetic resonance imaging (MRI) has gained a great importance in
      this setting of disease, being able to determine the presence of local recurrence
      with high sensitivity, also in the presence of low serum PSA levels. Lastly, the
      introduction of positron emission tomography/computed tomography (PET/CT) with
      radiolabeled choline agents let to improve the management of patients with early
      recurrence of disease, although its accuracy is linked to the PSA and PSA dynamic
      values. New radiopharmaceutical agents, like 68Ga-PSMA or 18F-FACBC and others
      could improve the diagnostic accuracy of PET/CT, but the data is still
      preliminary. In the present review we will discuss both clinical and diagnostic
      instrumentations, actually available in clinical practice, able to early identify
      the presence of recurrent PCa and to differentiate between local and distant
      relapse of tumor. 

PMID- 26213141
TI  - Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory
      lymphoma.
AB  - We conducted a phase II study of the AKT inhibitor, MK2206 in patients with
      relapsed or refractory lymphoma of any histology excluding Burkitt lymphoma or
      lymphoblastic lymphoma. MK-2206 was administered orally at 200 mg once weekly in
      28-d cycles up to 12 cycles in the absence of progression or significant
      toxicity. The dose was adjusted based on tolerance. A total of 59 patients were
      enrolled. The final doses patients received were 300 mg (n = 33), 250 mg (n = 2),
      200 mg (n = 16) and 135 mg (n = 8). Based on intent-to-treat analysis, objective
      response was observed in 8 (14%) patients (2 complete response and 6 partial
      response), with median response duration of 5.8 months. The overall response rate
      was 20% in 25 patients with classical Hodgkin lymphoma. Rash was the most common
      toxicity (any grade 53%, Grade 3 in 15%) and was observed in a dose-dependent
      manner. The correlative cytokine analysis showed paradoxical increase in several
      cytokines, which may be explained by negative feedback mechanism induced by the
      on-target effect of AKT inhibitor. Our data demonstrate that MK2206 has a
      favourable safety profile with a modest activity in patients with relapsed
      Hodgkin lymphoma. The future studies should explore mechanism-based combinations
      (clinicaltrials.gov NCT01258998). 

PMID- 26213145
TI  - A Nonlinear Least Squares Approach to Time of Death Estimation Via Body Cooling.
AB  - The problem of time of death (TOD) estimation by body cooling is revisited by
      proposing a nonlinear least squares approach that takes as input a series of
      temperature readings only. Using a reformulation of the Marshall-Hoare double
      exponential formula and a technique for reducing the dimension of the state
      space, an error function that depends on the two cooling rates is constructed,
      with the aim of minimizing this function. Standard nonlinear optimization methods
      that are used to minimize the bivariate error function require an initial guess
      for these unknown rates. Hence, a systematic procedure based on the given
      temperature data is also proposed to determine an initial estimate for the rates.
      Then, an explicit formula for the TOD is given. Results of numerical simulations
      using both theoretical and experimental data are presented, both yielding
      reasonable estimates. The proposed procedure does not require knowledge of the
      temperature at death nor the body mass. In fact, the method allows the estimation
      of the temperature at death once the cooling rates and the TOD have been
      calculated. The procedure requires at least three temperature readings, although
      more measured readings could improve the estimates. With the aid of computerized
      recording and thermocouple detectors, temperature readings spaced 10-15 min
      apart, for example, can be taken. The formulas can be straightforwardly
      programmed and installed on a hand-held device for field use.

PMID- 26213142
TI  - Social support and mental health among adults prior to HIV counseling and testing
      in Durban, South Africa.
AB  - Poor social support and mental health may be important modifiable risk factors
      for HIV acquisition, but they have not been evaluated prior to HIV testing in
      South Africa. We sought to describe self-perceived mental health and social
      support and to characterize their independent correlates among adults who
      presented for voluntary HIV testing in Durban. We conducted a large cross
      sectional study of adults (>=18 years of age) who presented for HIV counseling
      and testing between August 2010 and January 2013 in Durban, South Africa. We
      enrolled adults presenting for HIV testing and used the Medical Outcomes Study's
      Social Support Scale (0 [poor] to 100 [excellent]) and the Mental Health
      Inventory (MHI-3) to assess social support and mental health. We conducted
      independent univariate and multivariable linear regression models to determine
      the correlates of lower self-reported Social Support Index and lower self
      reported MCH scores. Among 4874 adults surveyed prior to HIV testing, 1887 (39%)
      tested HIV-positive. HIV-infected participants reported less social support (mean
      score 66 +/- 22) and worse mental health (mean score 66 +/- 16), compared to HIV
      negative participants (74 +/- 21; 70 +/- 18; p < 0.0001). In a multivariable
      analysis, significant correlates of less social support included presenting for
      HIV testing at an urban hospital, not having been tested previously, not working
      outside the home, and being HIV-infected. In a separate multivariable analysis,
      significant correlates of poor mental health were similar, but also included HIV
      testing at an urban hospital and being in an intimate relationship less than six
      months. In this study, HIV-infected adults reported poorer social support and
      worse mental health than HIV-negative individuals. These findings suggest that
      interventions to improve poor social support and mental health should be focused
      on adults who do not work outside the home and those with no previous HIV
      testing. 

PMID- 26213140
TI  - Prostate-specific membrane antigen as a target for cancer imaging and therapy.
AB  - The prostate-specific membrane antigen (PSMA) is a molecular target whose use has
      resulted in some of the most productive work toward imaging and treating prostate
      cancer over the past two decades. A wide variety of imaging agents extending from
      intact antibodies to low-molecular-weight compounds permeate the literature. In
      parallel there is a rapidly expanding pool of antibody-drug conjugates,
      radiopharmaceutical therapeutics, small-molecule drug conjugates, theranostics
      and nanomedicines targeting PSMA. Such productivity is motivated by the abundant
      expression of PSMA on the surface of prostate cancer cells and within the
      neovasculature of other solid tumors, with limited expression in most normal
      tissues. Animating the field is a variety of small-molecule scaffolds upon which
      the radionuclides, drugs, MR-detectable species and nanoparticles can be placed
      with relative ease. Among those, the urea-based agents have been most extensively
      leveraged, with expanding clinical use for detection and more recently for
      radiopharmaceutical therapy of prostate cancer, with surprisingly little
      toxicity. PSMA imaging of other cancers is also appearing in the clinical
      literature, and may overtake FDG for certain indications. Targeting PSMA may
      provide a viable alternative or first-line approach to managing prostate and
      other cancers. 

PMID- 26213146
TI  - Assessment of polyaromatic hydrocarbons and pesticide residues in domestic and
      imported pangasius (Pangasianodon hypophthalmus) fish in India.
AB  - BACKGROUND: The pangasius catfish (Pangasianodon hypophthalmus) is a ubiquitous
      item of seafood in global markets. However, pesticide residues in aquaculture
      fish, arising from agricultural run-off and/or direct application during pond
      preparation, pest control and harvest, are a potential food safety concern. This
      study assessed the level of chemical hazard in domestic and imported pangasius
      fish in India. RESULTS: A total of 119 contaminants, including polyaromatic
      hydrocarbons (PAHs), organochlorines (OCs) and other groups of pesticides, were
      screened in 148 samples during 2014-2015 as the first endeavour of its kind in an
      Indian context, employing a validated gas chromatography/tandem mass spectrometry
      (GC/MS/MS) method. Apart from the low-level incidence of OCs, pesticides such as
      quinalphos, malathion, parathion-methyl, etc. were detected in 38% of the
      samples. In comparison with Indian pangasius, fewer contaminants at low residue
      level were detected in pangasius fillets imported from Vietnam. CONCLUSION: The
      human dietary exposures of the residue concentrations detected were less than the
      maximum permissible intakes and hence appeared safe. However, detection of
      commonly used pesticides indicated their direct application in aquaculture and
      contamination from agricultural run-off. This emphasizes the need for continual
      residue monitoring in aquaculture fish. (c) 2015 Society of Chemical Industry.

PMID- 26213147
TI  - Decision precision or holistic heuristic?: Insights on on-site selection of
      student nurses and midwives.
AB  - Concerns about quality of care delivery in the UK have led to more scrutiny of
      criteria and methods for the selection of student nurses. However few substantive
      research studies of on-site selection processes exist. This study elicited and
      interpreted perspectives on interviewing processes and related decision making
      involved in on-site selection of student nurses and midwives. Individual and
      focus group interviews were undertaken with 36 lecturers, 5 clinical staff and 72
      students from seven Scottish universities. Enquiry focused primarily on
      interviewing of candidates on-site. Qualitative content analysis was used as a
      primary strategy, followed by in-depth thematic analysis. Students had very mixed
      experiences of interview processes. Staff typically took into account a range of
      candidate attributes that they valued in order to achieve holistic assessments.
      These included: interpersonal skills, team working, confidence, problem-solving,
      aptitude for caring, motivations, and commitment. Staff had mixed views of the
      validity and reliability of interview processes. A holistic heuristic for overall
      decision making predominated over belief in the precision of, and evidence base
      for, particular attribute measurement processes. While the development of
      measurement tools for particular attributes continues apace, tension between
      holism and precision is likely to persist within on-site selection procedures. 

PMID- 26213148
TI  - Professional development utilizing an oncology summer nursing internship.
AB  - The aim of this study was to examine the effect of an oncology student nursing
      internship on role socialization and professional self-concept. This mixed
      methods study utilized a convergent parallel approach that incorporated a quasi
      experimental and qualitative design. Data was collected through pre and post
      survey and open-ended questions. Participants were 11 baccalaureate nursing
      students participating in a summer oncology student nursing internship between
      their junior and senior years. Investigators completed a content analysis of
      qualitative questionnaires resulted in categories of meaning, while the Wilcoxon
      signed-ranks test was used to compare pre and post internship scores. Aggregated
      mean scores from all instruments showed an increase in professionalism, role
      socialization, and sense of belonging from pre to post-internship, although no
      differences were significant. Qualitative data showed participants refined their
      personal philosophy of nursing and solidified their commitment to the profession.
      Participants did indicate, however, that the internship, combined with weekly
      debriefing forums and conferences, proved to have a positive impact on the
      students' role socialization and sense of belonging. Despite quantitative
      results, there is a need for longitudinal research to confirm the effect of
      nursing student internships on the transition from student to professional. 

PMID- 26213149
TI  - Structural Perspectives on the Evolutionary Expansion of Unique Protein-Protein
      Binding Sites.
AB  - Structures of protein complexes provide atomistic insights into protein
      interactions. Human proteins represent a quarter of all structures in the Protein
      Data Bank; however, available protein complexes cover less than 10% of the human
      proteome. Although it is theoretically possible to infer interactions in human
      proteins based on structures of homologous protein complexes, it is still unclear
      to what extent protein interactions and binding sites are conserved, and whether
      protein complexes from remotely related species can be used to infer interactions
      and binding sites. We considered biological units of protein complexes and
      clustered protein-protein binding sites into similarity groups based on their
      structure and sequence, which allowed us to identify unique binding sites. We
      showed that the growth rate of the number of unique binding sites in the Protein
      Data Bank was much slower than the growth rate of the number of structural
      complexes. Next, we investigated the evolutionary roots of unique binding sites
      and identified the major phyletic branches with the largest expansion in the
      number of novel binding sites. We found that many binding sites could be traced
      to the universal common ancestor of all cellular organisms, whereas relatively
      few binding sites emerged at the major evolutionary branching points. We analyzed
      the physicochemical properties of unique binding sites and found that the most
      ancient sites were the largest in size, involved many salt bridges, and were the
      most compact and least planar. In contrast, binding sites that appeared more
      recently in the evolution of eukaryotes were characterized by a larger fraction
      of polar and aromatic residues, and were less compact and more planar, possibly
      due to their more transient nature and roles in signaling processes. 

PMID- 26213150
TI  - Echocardiographic assessment of right ventricular systolic function in conscious
      healthy dogs following a single dose of pimobendan versus atenolol.
AB  - OBJECTIVE: To quantify drug-induced changes in right ventricular (RV) systolic
      function after administration of pimobendan and atenolol. ANIMALS: 80 healthy
      privately-owned dogs. METHODS: Using a prospective, blinded, fully-crossed study
      design with randomized drug administration, RV systolic function was determined
      twice at two time periods; before and 3 h after administration of pimobendan
      (0.25 mg/kg PO) or atenolol (1 mg/kg PO). Indices of RV systolic function
      included tricuspid annular plane systolic excursion (TAPSE), fractional area
      change (FAC), pulsed-wave tissue Doppler-derived systolic myocardial velocity of
      the lateral tricuspid annulus (S'), and speckle-tracking-derived global
      longitudinal RV free wall strain and strain rate. The effect of treatment on
      percent change from baseline RV function was analyzed with a linear mixed model
      including the covariates heart rate, body weight, age, gender, drug sequence, and
      time period. RESULTS: All indices showed a significant (p < 0.0001) increase and
      decrease from baseline following pimobendan and atenolol, respectively.
      Significant differences from baseline were attributed to drug treatment (p <
      0.0001); whereas, effects of other covariates were not significant. The greatest
      percent changes, but also highest variability, were observed for S' and strain
      rate (p < 0.0001). Post-atenolol, a significantly greater proportion of dogs
      exceeded the repeatability coefficient of variation for FAC and S' compared to
      TAPSE (p <= 0.007). CONCLUSIONS: Echocardiographic indices in healthy dogs
      tracked expected changes in RV systolic function following pimobendan and
      atenolol and warrant study in dogs with cardiovascular disease.

PMID- 26213151
TI  - Heat and hydration status: Predictors of repeated measures of urine specific
      gravity among Tsimane' adults in the Bolivian Amazon.
AB  - OBJECTIVE: Hydration status is critical to physiological and cognitive health,
      yet it is unclear how populations living in hot-humid environments experiencing
      lifestyle transitions manage this underexplored facet of heat adaptation. This
      study assesses the predictors of repeated measures of hydration status for adults
      from two villages (close and distant from a market town) in the Bolivian Amazon.
      MATERIALS AND METHODS: Interviews and focal follows were conducted with 36
      Tsimane' (50% male). Urine samples, temperature, activity levels, and
      anthropometrics were measured pre-interview and post-follow and yielded a small
      panel (72 observations). Urine samples were analyzed for urine specific gravity
      (USG), a biomarker of hydration, with a refractometer. RESULTS: The mean USG was
      1.020 g/ml (SD +/- 0.008) with men (1.022 +/- 0.008) slightly more dehydrated
      than women (1.018 +/- 0.007). Using 1.020 as the criteria for clinical
      dehydration, 42% of the participants were dehydrated at both intervals and 21%
      were extremely dehydrated. Controlling for activity level, village membership,
      and covariates in random-effects linear regression models, each degree centigrade
      increase was associated with a USG increase of 0.0008 g/ml (P = 0.000). Adults
      from the village closer to the market town had significantly higher USG (B =
      0.0041; P = 0.04) than those in the distant village. Dehydration was predicted to
      occur at 29 degrees C, just above the thermoneutral range, and extreme
      dehydration at 37 degrees C. DISCUSSION: These findings suggest that hotter
      temperatures coupled with lifestyle transitions may create conditions that
      increase vulnerability to dehydration among rural populations through landscape
      modifications and diet changes.

PMID- 26213152
TI  - Biomimetic phantom for cardiac diffusion MRI.
AB  - PURPOSE: Diffusion magnetic resonance imaging (MRI) is increasingly used to
      characterize cardiac tissue microstructure, necessitating the use of
      physiologically relevant phantoms for methods development. Existing phantoms are
      generally simplistic and mostly simulate diffusion in the brain. Thus, there is a
      need for phantoms mimicking diffusion in cardiac tissue. MATERIALS AND METHODS: A
      biomimetic phantom composed of hollow microfibers generated using co
      electrospinning was developed to mimic myocardial diffusion properties and fiber
      and sheet orientations. Diffusion tensor imaging was carried out at monthly
      intervals over 4 months at 9.4T. 3D fiber tracking was performed using the
      phantom and compared with fiber tracking in an ex vivo rat heart. RESULTS: The
      mean apparent diffusion coefficient and fractional anisotropy of the phantom
      remained stable over the 4-month period, with mean values of 7.53 +/- 0.16 * 10(
      4) mm(2) /s and 0.388 +/- 0.007, respectively. Fiber tracking of the 1st and 3rd
      eigenvectors generated analogous results to the fiber and sheet-normal direction
      respectively, found in the left ventricular myocardium. CONCLUSION: A biomimetic
      phantom simulating diffusion in the heart was designed and built. This could aid
      development and validation of novel diffusion MRI methods for investigating
      cardiac microstructure, decrease the number of animals and patients needed for
      methods development, and improve quality control in longitudinal and multicenter
      cardiac diffusion MRI studies.

PMID- 26213154
TI  - Spontaneous Regeneration of Human Photoreceptor Outer Segments.
AB  - Photoreceptors are damaged in many common eye diseases, such as macular
      degeneration, retinal detachment, and retinitis pigmentosa. The development of
      methods to promote the repair or replacement of affected photoreceptors is a
      major goal of vision research. In this context, it would be useful to know
      whether photoreceptors are capable of undergoing some degree of spontaneous
      regeneration after injury. We report a subject who lost retinal function in a
      wide zone around the optic disc, giving rise to massive enlargement of the
      physiological blind spot. Imaging with an adaptive optics scanning laser
      ophthalmoscope (AOSLO) showed depletion of cone outer segments in the affected
      retina. A year later visual function had improved, with shrinkage of the enlarged
      blind spot. AOSLO imaging showed repopulation of cone outer segments, although
      their density remained below normal. There was a one-to-one match between sites
      of formerly missing outer segments and new outer segments that had appeared over
      the course of the year's recovery. This correspondence provided direct
      morphological evidence that damaged cones are capable, under some circumstances,
      of generating new outer segments. 

PMID- 26213155
TI  - Continuities and changes in infant attachment patterns across two generations.
AB  - This study examined the intergenerational continuities and changes in infant
      attachment patterns within a higher-risk longitudinal sample of 55 female
      participants born into poverty. Infant attachment was assessed using the Strange
      Situation when participants were 12 and 18 months as well as several decades
      later with participants' children. Paralleling earlier findings from this sample
      on the stability of attachment patterns from infancy to young adulthood, results
      provided evidence for intergenerational continuities in attachment
      disorganization but not security. Children of adults with histories of infant
      attachment disorganization were at an increased risk of forming disorganized
      attachments. Although changes in infant attachment patterns across the two
      generations were not correlated with individuals' caregiving experiences or
      interpersonal stresses and supports during childhood and adolescence, higher
      quality social support during adulthood was associated with intergenerational
      changes from insecure to secure infant-caregiver attachment relationships. 

PMID- 26213156
TI  - The change of pharmacokinetics of fexofenadine enantiomers through the single and
      simultaneous grapefruit juice ingestion.
AB  - The stereoselective pharmacokinetics of fexofenadine are associated with OATP2B1
      mediated transport, and grapefruit juice (GFJ) is an inhibitor of OATP2B1.
      Therefore, in this study, we aimed to investigate whether and to what extent GFJ
      ingestion affected the pharmacokinetics of fexofenadine enantiomers in healthy
      subjects. In a randomized, two-phase, open-label, crossover study, 14 subjects
      received 60 mg of racemic fexofenadine simultaneously with water or GFJ.
      Ingestion of GFJ significantly decreased the areas under the plasma concentration
      time curve (AUC0-24) for (R)- and (S)-fexofenadine by 39% and 52%, respectively.
      Subsequently, GFJ increased the mean R/S ratio of the AUC0-24 from 1.58 to 1.96
      (P < 0.05). Although GFJ greatly reduced the amounts of (R)- and (S)-fexofenadine
      excreted into the urine (Ae0-24) by 52% and 61%, respectively, the mean R/S
      ratios of Ae0-24 and the renal clearances of both enantiomers were unchanged
      between the control and GFJ phases. GFJ, an OATP2B1 inhibitor, significantly
      reduced the plasma concentrations of fexofenadine enantiomers, exhibiting
      clinically moderate effects. The present results suggested that changes in
      OATP2B1 activity by GFJ may alter the stereoselective pharmacokinetics of
      fexofenadine and that reduced intestinal OATP2B1 activity may affect the
      stereoselectivity of fexofenadine. 

PMID- 26213157
TI  - Polymorphisms of ABCG2, ABCB1 and HNF4alpha are associated with Lamotrigine
      trough concentrations in epilepsy patients.
AB  - Lamotrigine (LTG) is commonly used to control seizure in epilepsy patients and
      with referenced therapeutic windows in clinical practice. This study is to
      identify and characterize the function of genetic variants that influence the
      trough concentrations of LTG in epilepsy patients following monotherapy regimen
      (37.5-250 mg/d). Twelve single nucleotide polymorphisms (SNPs) involved in LTG
      metabolism and transport pathways, including UGT2B7, ABCB1, ABCG2, NR1I2 and
      HNF4alpha were genotyped in 140 Chinese epilepsy patients. Steady-state trough
      concentration of LTG was measured by a high-performance liquid chromatography
      method. Polymorphisms in ABCG2 rs2231142, rs3114020, HNF4alpha rs2071197 and
      ABCB1 rs1128503 were found to be associated with LTG CDR (concentration/dose
      normalized by body weight). In addition, multiple linear regression analysis
      revealed that ABCG2 rs2231142 had a remarkable effect on LTG concentrations which
      is stated to be 4.8% of the variability of LTG and may also help to interpret
      ethnic difference in LTG pharmacokinetics. Our findings provided new insights
      that SNPs of genes involved in the transport of LTG contribute to interpatient
      variation in LTG pharmacokinetics. Future studies are necessary to determine
      whether these SNPs can be used to provide LTG dosing guidance and influence
      seizure control and adverse reaction of LTG. 

PMID- 26213158
TI  - Ankle arthritis predicts polyarticular disease course and unfavourable outcome in
      children with juvenile idiopathic arthritis.
AB  - OBJECTIVES: To evaluate the occurrence, clinical characteristics and prognostic
      factors associated with ankle arthritis in children with juvenile idiopathic
      arthritis (JIA). METHODS: 440 children with JIA were followed for eight years in
      a prospective Nordic population-based cohort study. Data on remission was
      available for 427 of these children. Occurrence of clinically assessed ankle
      arthritis was analysed in relation to JIA category, clinical characteristics and
      remission data eight years after disease onset. RESULTS: In 440 children with
      JIA, 251 (57%) experienced ankle arthritis during the first eight years of
      disease. Ankle arthritis was least common in the persistent oligoarticular
      category (25%) and most common in children with extended oligoarticular (83%) and
      polyarticular RF-negative (85%) JIA. Children who developed ankle arthritis
      during the first year of disease were younger at disease onset (median age 4.9
      (IQR 2.1-8.8) vs. 6.6 (IQR 2.8-10.1) years, p<0.003) and had more cumulative
      affected joints at 8-year follow-up (median involved joints 10 (IQR 6-16) vs. 3
      (IQR 2-9), p<0.001). The odds ratio for not achieving remission eight years after
      disease onset, if the ankle joint was involved during the first year of disease
      was 2.0 (95 % CI:1.3-3.0, p<0.001). Hind-, mid- and forefoot involvements were
      more common compared to patients without ankle arthritis. CONCLUSIONS: In this
      Nordic population-based 8-year follow-up study, occurrence of ankle arthritis
      during the first year was associated with an unfavourable disease outcome. We
      suggest that ankle arthritis should be recognised in the assessment of prognosis
      and choice of treatment strategy in JIA.

PMID- 26213159
TI  - National Trends in Foot and Ankle Arthrodesis: 17-Year Analysis of the National
      Survey of Ambulatory Surgery and National Hospital Discharge Survey.
AB  - Foot and ankle arthrodesis reliably reduces pain and functional disability among
      patients with arthritis and deformity. Since its introduction in 1953,
      improvements in surgical technique have enhanced the outcomes and reduced
      complications. However, little is known regarding US national trends of foot and
      ankle arthrodesis. The present study sought to use the most recently available
      Centers for Disease Control and Prevention data to investigate changes in the
      usage of inpatient and ambulatory foot and ankle arthrodesis. Cases of foot and
      ankle arthrodesis were identified using the National Hospital Discharge Survey
      and National Survey of Ambulatory Surgery, and the data were analyzed for trends
      in demographics, treatment, and usage. From 1994 to 2006, the population-adjusted
      rates of foot and ankle arthrodeses increased by 146% (8.2/100,000 capita to
      20.2/100,000 capita). The number of outpatient arthrodeses performed with
      arthroscopic assistance increased by 858%. The population-adjusted rate of
      outpatient and inpatient procedures increased by 415% and 17%, respectively. The
      gender-adjusted rates increased by 59% for males and 209% for females. The age
      adjusted rates increased among patients >35 years old in both settings. The use
      of peripheral nerve blocks during ambulatory procedures increased from 3.3% to
      10.1%. Private insurance was the largest compensator. In conclusion, the rate of
      foot and ankle arthrodesis increased dramatically from 1990 to 2007 using the
      most up-to-date publicly available data. Knowledge of these national practice
      patterns could aid policy-makers and surgeons in appropriately allocating
      healthcare resources to ensure quality patient care. 

PMID- 26213160
TI  - A Specialized Fibular Locking Plate for Lateral Malleolar Fractures.
AB  - We evaluated the outcomes and complications of a specialized fibular locking
      plate in the treatment of lateral malleolar fractures. The study included 27
      patients (13 males and 14 females; mean age 46, range 16 to 73 years) with a
      minimum 1-year follow-up period. The study included 9 (33%) isolated lateral
      malleolar, 6 (23%) bimalleolar, 10 (37%) trimalleolar fractures, and 2 (7%) pilon
      fractures, all of which were treated using a specialized fibular locking plate
      for internal fixation. Bony union was monitored, and the patients' objective
      satisfaction was evaluated using the EQ-5D questionnaire (EuroQol Group). The
      patients were followed up after 1 year, and bony union was confirmed using a
      simple radiograph. The EQ-5D median +/- standard deviation was 70 +/- 15 (range
      40 to 90) points at discharge, 80 +/- 13 (range 40 to 90) at 6 weeks, 85 +/- 11
      (range 50 to 90) at 3 months, 90 +/- 8 (range 60 to 90) at 6 months, and 90 +/- 9
      (range 70 to 95) at 1 year. Therefore, the EQ-5D score increased with time. No
      significant difference was found when stratified by sex or age (Mann-Whitney U
      test, p < .05). Eight complications (29%) developed: 1 superficial infection at
      the operative site, 1 case (3%) of osteomyelitis, 2 cases (7%) of an
      osteochondral lesion of the talus, and 5 cases (19%) of metallosis. A specialized
      fibular locking plate has the advantages of being an easy procedure, providing
      good patient satisfaction, and achieving complete bony union in all patients.
      However, additional complications developed compared with other well-known
      methods for fibular fracture treatment. 

PMID- 26213161
TI  - Fracture of the Posterior Process of the Talus With Concomitant Subtalar
      Dislocation.
AB  - Fracture of the posterior process of the talus with concomitant subtalar
      dislocation is rare; thus, the mechanism of injury, appropriate treatment, and
      prognosis are unclear. We report the case of a 50-year-old male with a fracture
      of the posterior process of the talus with concomitant subtalar dislocation that
      was recognized early and successfully treated operatively. 

PMID- 26213162
TI  - Functional Outcomes After Gunshot Wounds to the Foot and Ankle.
AB  - The peer-reviewed, clinical data focusing on foot and ankle gunshot wounds are
      limited. The present study aimed to evaluate functional outcomes in a case series
      according to the area of injury, articular involvement, and the presence of
      infection. From January 2003 through February 2011 (8 years), 37 patients treated
      at Sinai-Grace Hospital (Detroit, MI) for civilian gunshot wounds localized to
      the foot and/or ankle were reviewed. Of these, 27 (72.97%) met the inclusion
      criteria. All acute wounds were thoroughly irrigated in the emergency room (8 of
      27, 29.63%) or operating room (19 of 27, 70.37%) within 1 hour of presentation.
      The injuries were categorized as either zone 1 or 2, if localized distally or
      proximally to the midtarsal joint, respectively. The Maryland Foot Score was
      recorded and compared based on the location, articular involvement, and infection
      status, using analysis of variance. The mean Maryland Foot Score in patients with
      zone 1 injuries was 89.3 (range 72 to 100) and in patients with zone 2 injures
      was 61.8 (range 13 to 97; p = .001). The mean Maryland Foot Score in patients
      with type A injuries was 93.1 (range 72 to 100) and in patients with type B
      injures was 69.2 (range 13 to 99; p = .001), regardless of location.
      Intraoperative cultures yielded Staphylococcus epidermidis (7 of 27, 25.93%) and
      Enterococcus cloacae (1 of 27, 3.7%). No cases of Pseudomonas aeruginosa were
      found, although 9 cases (33.33%) involved shoe penetration. One third of the
      cases (9 of 27) yielded intra-articular pain, of which 4 (14.82%) required joint
      arthrodesis.

PMID- 26213163
TI  - Extensive Loss of Tibialis Anterior Tendon: Surgical Repair With Split Tendon
      Transfer of Tibialis Posterior Tendon: A Case Report.
AB  - Extensive damage of the tibialis anterior tendon is rare and mainly caused by
      trauma. Surgical treatment of these injuries can become challenging owing to the
      limited availability of autogenous graft resources for reconstruction of the
      defect. In the present case report, we describe a large defect in the midfoot
      soft tissue after a traffic injury, which included complete loss of the tibialis
      anterior tendon. The tendon was reconstructed by split tendon transfer of the
      tibialis posterior tendon without sacrificing function, which was confirmed by
      the follow-up examination at 6 years after injury. We believe split tendon
      transfer of the tibialis posterior tendon can be one of the treatment options for
      patients with extensive disruption of the tibialis anterior tendon. 

PMID- 26213164
TI  - Infectious Achilles Tendinitis After Local Injection of Human Placental Extracts:
      A Case Report.
AB  - Local injections of corticosteroids or human placental extracts are sometimes
      used for the treatment of resistant tendinitis or fasciitis. We report a case of
      infectious Achilles tendinitis complicated by calcaneal osteomyelitis after
      injection of human placental extracts for the Achilles tendinitis. She was
      treated with excision of the infected bone and tendon, followed by V-Y
      lengthening of the proximal portion of the Achilles tendon in a single stage. At
      2 years postoperative, she remained symptom free without any signs of recurrence,
      and the follow-up magnetic resonance imaging scan demonstrated a well-maintained
      Achilles tendon with normal signal intensity. 

PMID- 26213165
TI  - Reconstruction of the Midfoot Using a Free Vascularized Fibular Graft After En
      Bloc Excision for Giant Cell Tumor of the Tarsal Bones: A Case Report.
AB  - We report the case of a 32-year-old Japanese female with a giant cell tumor of
      bone involving multiple midfoot bones. Giant cell tumors of bone account for
      approximately 5% of all primary bone tumors and most often arise at the ends of
      long bones. The small bones, such as those of the hands and feet, are rare sites
      for giant cell tumors. Giant cell tumors of the small bones tend to exhibit more
      aggressive clinical behavior than those of the long bones. The present patient
      underwent en bloc tumor excision involving multiple tarsals and metatarsals. We
      reconstructed the longitudinal arch of the foot with a free vascularized fibular
      graft. At the 2-year follow-up visit, bony union had been achieved, with no tumor
      recurrence. 

PMID- 26213169
TI  - ?

PMID- 26213168
TI  - Structure Elucidation and Characterization of Different Thyroxine Polymorphs.
AB  - Thyroid hormones regulate almost every process in the body, including body
      temperature, growth, and heart rate. They influence carbohydrate metabolism,
      protein synthesis and breakdown, and cardiovascular, renal, and brain function.
      Two new polymorphs of synthetic L-thyroxine (T4) are reported and the effect of
      polymorphism on the solubility of this important hormone is shown. Conformational
      changes were also discovered to have a remarkable effect on the strength of
      halogen bonding and the reactivity of the C-I bonds, which could have a
      significant effect on the hormone activity.

PMID- 26213170
TI  - ?

PMID- 26213167
TI  - Comparing the Cost of Caring for Medicare Beneficiaries in Federally Funded
      Health Centers to Other Care Settings.
AB  - OBJECTIVE: To compare total annual costs for Medicare beneficiaries receiving
      primary care in federally funded health centers (HCs) to Medicare beneficiaries
      in physician offices and outpatient clinics. DATA SOURCES/STUDY SETTINGS: Part A
      and B fee-for-service Medicare claims from 14 geographically diverse states. The
      sample was restricted to beneficiaries residing within primary care service areas
      (PCSAs) with at least one HC. STUDY DESIGN: We modeled separately total annual
      costs, annual primary care costs, and annual nonprimary care costs as a function
      of patient characteristics and PCSA fixed effects. DATA COLLECTION: Data were
      obtained from the Centers for Medicare & Medicaid Services. PRINCIPAL FINDINGS:
      Total median annual costs (at $2,370) for HC Medicare patients were lower by 10
      percent compared to patients in physician offices ($2,667) and by 30 percent
      compared to patients in outpatient clinics ($3,580). This was due to lower
      nonprimary care costs in HCs, despite higher primary care costs. CONCLUSIONS: HCs
      may offer lower total cost practice style to the Centers for Medicare & Medicaid
      Services, which administers Medicare. Future research should examine whether
      these lower costs reflect better management by HC practitioners or more limited
      access to specialty care by HC patients.

PMID- 26213171
TI  - ?

PMID- 26213172
TI  - ?

PMID- 26213173
TI  - ?

PMID- 26213175
TI  - ?

PMID- 26213174
TI  - ?

PMID- 26213176
TI  - ?

PMID- 26213177
TI  - Risk assessment and regulation of D5 in Canada: Lessons learned.

PMID- 26213178
TI  - Comparison of hospital length of stay between hospitalized non-valvular atrial
      fibrillation patients treated with either apixaban or warfarin.
AB  - BACKGROUND: Hospital length of stay (LOS) is an important cost driver for
      hospitals and payers alike. Hospitalized non-valvular atrial fibrillation (NVAF)
      patients treated with apixaban may have shorter LOS than those treated with
      warfarin because of the absence of need for INR monitoring in apixaban. Thus,
      this study compared hospital LOS between hospitalized NVAF patients treated with
      either apixaban or warfarin. METHODS: This was a retrospective, observational
      cohort study based on a large US database including diagnosis, procedure, and
      drug administration information from >600 acute-care hospitals. Patients selected
      for study were aged >=18 years and had a hospitalization record with an ICD-9-CM
      diagnosis code for atrial fibrillation (AF) in any position from 1 January 2013
      to 28 February 2014 (index hospitalization). Patients with diagnoses indicative
      of rheumatic mitral valvular heart disease or a valve replacement procedure
      during index hospitalization were excluded. Patients were required to have been
      treated with either apixaban or warfarin, and not treated with rivaroxaban or
      dabigatran, during index hospitalization. Apixaban patients were propensity score
      (PS) matched to warfarin patients at a 1:1 ratio, using patient
      demographic/clinical and hospital characteristics. The study outcome was hospital
      LOS, calculated as discharge date minus admission date; a sensitivity analysis
      calculated hospital LOS as discharge date minus first anticoagulant
      administration date. Sub-analyses were conducted among patients with a primary
      diagnosis of AF. RESULTS: The study included 832 apixaban patients matched to 832
      warfarin patients. Mean [standard deviation (SD)] and median hospital LOS were
      significantly (p < 0.001) shorter in apixaban patients (4.5 [4.2] and 3 days)
      than in warfarin patients (5.4 [5.0] and 4). Results were consistent in the
      sensitivity and sub-analyses. CONCLUSIONS: Among NVAF patients, apixaban
      treatment was associated with shorter hospital LOS when compared with warfarin
      treatment. These findings may have important clinical and economic implications
      for hospitals, payers, and patients.

PMID- 26213179
TI  - Molecular Structures of Isomeric Ortho, Meta, and Para Bromo-Substituted alpha
      Methylsulfonyl-alpha-diethoxyphosphoryl Acetophenones by X-ray and DFT Molecular
      Orbital Calculations.
AB  - The X-ray single crystal analysis of isomeric ortho, meta, and para bromo
      substituted alpha-methylsulfonyl-alpha-diethoxyphosphoryl acetophenones showed
      that this class of compound adopts synclinal (gauche) conformations for both [
      P(O)(OEt)2] and [-S(O)2Me] groups, with respect to the carbonyl functional group.
      The phosphonate, sulfonyl, and carbonyl functional groups are joined through an
      intramolecular network of attractive interactions, as detected by molecular
      orbital calculations at the M06-2X/6-31G(d,p) level. These interactions are
      responsible for the more stable conformations in the gas phase, which also
      persist in the solid-state structures. The main structural distinction in the
      title compounds relates to the torsion angle of the aryl group (with respect to
      the carbonyl group), which gives rise to different interactions in the crystal
      packing, due to the different positions of the Br atom. 

PMID- 26213180
TI  - Passively mode-locked fiber laser by a cell-type WS2 nanosheets saturable
      absorber.
AB  - A cell-type saturable absorber has been demonstrated by filling the single mode
      photonic crystal fiber (SMPCF) with tungsten disulfide (WS2) nanosheets. The
      modulation depth, saturable intensity, and non-saturable loss of this SA are
      measured to be 3.53%, 159 MW/cm(2) and 23.2%, respectively. Based on this SA, a
      passively mode-locked EDF laser has been achieved with pulse duration of 808 fs
      and repetition rate of 19.57 MHz, and signal-noise-ratio (SNR) of 60.5 dB. Our
      results demonstrate that the cell-type WS2 nanosheets SA can serve as a good
      candidate for short-pulse mode locker. 

PMID- 26213181
TI  - Editorial Comment to Transperitoneal versus extraperitoneal robot-assisted
      laparoscopic radical prostatectomy: A prospective single surgeon randomized
      comparative study.

PMID- 26213182
TI  - Response and tolerance to oral vasodilator up-titration after intravenous
      vasodilator therapy in advanced decompensated heart failure.
AB  - AIMS: The aim of this study was to assess the haemodynamic response and tolerance
      to aggressive oral hydralazine/isosorbide dinitrate (HYD/ISDN) up-titration after
      intravenous vasodilator therapy in advanced decompensated heart failure (ADHF).
      METHODS AND RESULTS: Medical records of 147 consecutive ADHF patients who
      underwent placement of a pulmonary artery catheter and received intravenous
      vasodilator therapy were reviewed. Intravenous sodium nitroprusside and sodium
      nitroglycerin as first-line agent for those with preserved blood pressures were
      utilized in 143 and 32 patients, respectively. Sixty-one percent of patients were
      converted to oral HYD/ISDN combination therapy through a standardized conversion
      protocol. These patients had a significantly higher admission mean pulmonary
      arterial wedge pressure compared with patients not converted (28 +/- 7 vs. 25 +/-
      8 mmHg, respectively; P-value 0.024). Beneficial haemodynamic response to
      decongestive therapy, defined as low cardiac filling pressures and cardiac index
      >=2.20 L/min/m(2) without emergent hypotension, was achieved in 32% and 29% of
      patients who did or did not receive oral HYD/ISDN, respectively (P-value 0.762).
      HYD/ISDN dosing was progressively and consistently decreased up to the moment of
      hospital discharge and during outpatient follow-up, primarily due to incident
      hypotension. CONCLUSION: The use of a standardized haemodynamically guided up
      titration protocol for conversion from intravenous to oral vasodilators may
      warrant subsequent dose reductions upon stabilization.

PMID- 26213183
TI  - Single cell mass cytometry reveals remodeling of human T cell phenotypes by
      varicella zoster virus.
AB  - The recent application of mass cytometry (CyTOF) to biology provides a 'systems'
      approach to monitor concurrent changes in multiple host cell factors at the
      single cell level. We used CyTOF to evaluate T cells infected with varicella
      zoster virus (VZV) infection, documenting virus-mediated phenotypic and
      functional changes caused by this T cell tropic human herpesvirus. Here we
      summarize our findings using two complementary panels of antibodies against
      surface and intracellular signaling proteins to elucidate the consequences of VZV
      mediated perturbations on the surface and in signaling networks of infected T
      cells. CyTOF data was analyzed by several statistical, analytical and
      visualization tools including hierarchical clustering, orthogonal scaling, SPADE,
      viSNE, and SLIDE. Data from the mass cytometry studies demonstrated that VZV
      infection led to 'remodeling' of the surface architecture of T cells, promoting
      skin trafficking phenotypes and associated with concomitant activation of T-cell
      receptor and PI3-kinase pathways. This method offers a novel approach for
      understanding viral interactions with differentiated host cells important for
      pathogenesis. 

PMID- 26213184
TI  - Effect of end-stage hip, knee, and ankle osteoarthritis on walking mechanics.
AB  - This study tested the hypothesis that the presence of isolated ankle (A-OA;
      N=30), knee (K-OA; N=20), or hip (H-OA; N=30) osteoarthritis (OA) compared to
      asymptomatic controls (N=15) would lead to mechanical changes in the affected
      joint but also in all other lower limb joints and gait overall. Stride length,
      stance and swing times, as well as joint angles and moments at the hip, knee, and
      ankle were derived from 3-D kinematic and kinetic data collected from seven self
      selected speed walking trial. Values were compared across groups using a 1*4
      ANCOVA, covarying for walking speed. With walking speed controlled, the results
      indicated a reduction in hip and knee extension and ankle plantar flexion in
      accordance with the joint affected. In addition, OA in one joint had strong
      effects on other joints. In both H-OA and K-OA groups the hip never passed into
      extension, and A-OA subjects significantly changed hip kinematics to compensate
      for lack of plantar flexion. Finally, OA in any joint led to lower peak vertical
      forces as well as extension and plantar flexion moments compared to controls. The
      presence of end-stage OA at various lower extremity joints results in
      compensatory gait mechanics that cause movement alterations throughout the lower
      extremity. This work reinforces our understanding of the complex interaction of
      joints of the lower limb and the importance of focusing on the mechanics of the
      entire lower limb when considering gait disability and potential interventions in
      patients with isolated OA. 

PMID- 26213185
TI  - Differences in activation properties of the hamstring muscles during overground
      sprinting.
AB  - The purpose of this study was to quantify activation of the biceps femoris (BF)
      and medial hamstring (MH) during overground sprinting. Lower-extremity kinematics
      and electromyography (EMG) of the BF and MH were recorded in 13 male sprinters
      performing overground sprinting at maximum effort. Mean EMG activity was
      calculated in the early stance, late stance, mid-swing, and late-swing phases.
      Activation of the BF was significantly greater during the early stance phase than
      the late stance phase (p<0.01). Activation of the BF muscle was significantly
      lower during the first half of the mid-swing phase than the other phases
      (p<0.05). The MH had significantly greater EMG activation relative to its
      recorded maximum values compared to that for the BF during the late stance
      (p<0.05) and mid-swing (p<0.01) phases. These results indicate that the BF shows
      high activation before and after foot contact, while the MH shows high activation
      during the late stance and mid-swing phases. We concluded that the activation
      properties of the BF and MH muscles differ within the sprinting gait cycle. 

PMID- 26213186
TI  - Significance of 18F-fluorocholine PET/CT positive pulmonary lesions in prostate
      cancer patients.
AB  - AIM: To assess the frequency and the significance of incidental pulmonary lesions
      with 18F-fluorocholine (18F-FCH) PET/CT in prostate cancer (PCa) patients.
      PATIENTS, METHODS: 225 consecutive PCa patients referred for 18F-FCH PET/CT
      (median age 68 years) were retrospectively evaluated for the presence of lesions
      in the lungs: 173 referred for restaging and 52 for initial staging regarding
      their high risk of extra prostatic extension. The final diagnosis was based on
      histopathological or on clinical and radiological follow-up. RESULTS: 13 patients
      had 18F-FCH positive pulmonary and 8 patients malignant lesions: 5 patients (38%)
      had a primary lung cancer (2 squamous cell carcinomas, 1 papillary
      adenocarcinoma, 1 typical pulmonary carcinoid, 1 bronchioloalveolar carcinoma)
      and 3 patients (23%) PCa metastases. Benign lesions were found in 5 subjects
      (38%). SUVmax and maximum diameter were neither significantly different in
      primary and metastatic tumors nor between malignant and benign lesions.
      CONCLUSIONS: Although our results suggest that incidental uptake in the lungs in
      PCa patients are nonspecific, their detection may have a significant impact on
      patient management knowing that more than 60% represent malignant disease.

PMID- 26213187
TI  - Evaluation of Lewis blood group antigens and secretor status in pemphigus
      vulgaris.
AB  - BACKGROUND: There has not been publication of any previous study about the role
      of secretory status or Lewis phenotypes in the mechanisms of pemphigus vulgaris
      (PV). AIM: To evaluate the frequencies of secretory status and Lewis phenotypes
      in patients with PV compared with healthy controls (HCs) in order determine their
      roles in this autoimmune disease. METHODS: In total, 50 patients and 100 age- and
      sex-matched HCs were selected to form the study population, and 2 mL blood were
      collected from each subject to identify their Lewis phenotype. In subjects with
      the Le(a-b-) phenotype, saliva was also collected to determine secretor status.
      RESULTS: The frequency of the nonsecretor (NS) phenotypes Le(a+b-) and Le(a-b-)
      together was significantly higher in patients than in HCs: 34/50 (68%)vs. 26/100
      (26%), respectively (P < 0.001). All the patients and HC subjects with the Le (a
      b-) phenotype were found to be NS by haemagglutination inhibition assay of saliva
      samples. CONCLUSION: Based on our results, it seems that Le/b-negative NS
      individuals are more susceptible to PV.

PMID- 26213188
TI  - Finding the Most Catalytically Active Platinum Clusters With Low Atomicity.
AB  - On a subnanometer scale, an only one-atom difference in a metal cluster may cause
      significant transitions in the catalytic activity due to the electronic and
      geometric configurations. We now report the atomicity-specific catalytic activity
      of platinum clusters with significantly small atomicity, especially below 20. The
      atomic coordination structure is completely different from that of the larger
      face-centered cubic (fcc) nanocrystals. Here, an electrochemical study on such
      small clusters, in which the atomicity ranged between 12 and 20, revealed Pt19 as
      the most catalytically active species. In combination with a theoretical study, a
      common structure that leads to a high catalytic performance is proposed. 

PMID- 26213189
TI  - Static and dynamic compression application and removal on the intervertebral
      discs of growing rats.
AB  - Fusionless implants are used to correct pediatric progressive spinal deformities,
      most of them spanning the intervertebral disc. This study aimed at investigating
      the effects of in vivo static versus dynamic compression application and removal
      on discs of growing rats. A microloading device applied compression. 48 immature
      rats (28 d.o.) were divided into two groups (43d, 53d). Each group included four
      subgroups: control (no surgery), sham (device installed without loading), static
      (0.2 MPa) and dynamic compressions (0.2 MPa +/- 30% with 0.1 Hz). In 43d
      subgroups, compression was applied for 15 days. In 53d subgroups, compression was
      followed by 10 days without loading. Disc heights, nucleus/annulus volumetric
      proportions and nucleus proteoglycan contents were analyzed using one-way ANOVA
      and post-hoc Tukey comparisons (p < 0.05). Disc heights of 43d and 53d static and
      dynamic loading rats were lower than shams (p < 0.05). Volumetric proportions
      remained similar. At 43d, nucleus proteoglycan contents increased in both static
      and dynamic loading rats. However, at 53d, static loading rats had lower
      proteoglycan content than dynamic loading rats (p < 0.05). Disc structure is
      altered following static compression removal, but nucleus proteoglycan content
      remaining elevated in dynamic group. Dynamic fusionless implants would better
      preserve disc integrity.

PMID- 26213190
TI  - [Diagnosis and diagnostic criteria of autoimmune pancreatitis].
AB  - In 1995 Yoshida et al proposed "autoimmune pancreatitis". Recent studies
      suggested the existence of two subtypes of autoimmune pancreatitis (AIP): type 1
      related with IgG4 as the pancreatic manifestation of IgG4-related disease (IgG4
      RD), and type 2 related with a granulocytic epithelial lesion. There were several
      diagnostic criteria. This review provides a overview of autoimmune pancreatitis
      from diagnostic criteria and diagnostic strategie.

PMID- 26213191
TI  - [The pathogenic role of macrophage in lupus nephritis].
AB  - Lupus nephritis is major manifestation of systemic lupus erythematosus and could
      cause nephrotic syndrome or chronic kidney disease might lead to end-stage renal
      failure. The pathogenesis of macrophage as well as lymphocyte impairment had been
      described in lupus nephritis. The interstitial macrophage accumulation and
      interstitial change or fibrosis is more important than glomerular immunoglobulin
      deposition or glomerular macrophage accumulation in terms of renal outcome and
      survival proportion. The expressions of macrophage associated proteins such as
      CCL2/MCP-1, MIP-1 family and their receptors, CCR2, CCR1 and CCR5 are major
      target of therapeutic strategy for improving renal illness. The blockade of these
      chemokines or chemokine receptors ameliorates renal impairment without reducing
      glomerular immunoglobulin deposition. Deletion of CSF-1 signaling pathway
      represented more excellent effect in experimental lupus nephritis. The effect of
      specific antagonist for macrophage associated proteins, specific thyrosine kinase
      inhibitor for macrophage signaling pathway on glomerulonephritis in lupus prone
      mice had been reported with evaluation of renal leukocyte infiltration, anti-DNA
      antibody reduction, the amount of proteinuria, and their survival. The depletion
      of macrophage could be useful therapeutic tool including M2 macrophage and have
      synergistic effect with other immunomodulating agents.

PMID- 26213192
TI  - [Difference in target antigens between central tolerance and peripheral tolerance
      deficiencies].
AB  - Failure of the immunotolerance mechanisms causes multiple organ-specific
      autoimmune disorders. Mutations of autoimmune regulator (AIRE) gene result in
      central immunotolerance deficiency named autoimmune polyendocrinopathy,
      candidiasis, ectodermal dystrophy (APECED). Mutations of FOXP3 genes cause
      regulatory T cell (Treg) deficiency named immune dysregulation,
      polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Because T cell
      tolerance influences B cell tolerance, autoantibodies seem to reflect the
      presence of autoreactive T cells with the same antigen specificity. To date many
      differences in both clinical features and autoantibody profiles have been
      described between APECED and IPEX syndrome. In addition to the differences in
      target organs, we have found differences in the target antigens in the same
      organ, small intestine, between both disorders; anti-autoimmune enteropathy
      related 75 kDa antigen (AIE-75) antibodies are specific to IPEX syndrome, whereas
      anti-tryptophan hydroxylase-1 (TPH-1) antibodies are specific to APECED. These
      facts suggest that immunotolerance to AIE-75 depends on the Treg, whereas the
      tolerance to TPH-1 depends on the central mechanisms. Furthermore, given the
      earlier onset and more serious clinical features of IPEX syndrome than APECED,
      physiological roles of Aire on the selection of Treg may be, if present, limited.

PMID- 26213193
TI  - Using proteomic and genomic methods to understand JDM.
AB  - Juvenile dermatomyositis is a complex illness characterized by
      vascular/perivascular inflammation, primarily in the skin and muscles. In this
      review, we discuss how proteomic and genomic technologies have expanded our
      understanding of the immune pathogenesis of this disease. We will also discuss
      further directions that the field may take to use existing and developing
      technologies to further our understanding of this often-perplexing disease.

PMID- 26213194
TI  - [The function and the significance of full-automated tests for detecting
      antiphospholipid antibodies].
AB  - Antiphospholipid antibodies (aPLs) are a group of heterogenous antibodies with
      immunological and functional variations that are detected in the sera of patients
      with antiphospholipid syndrome (APS). Detection of these antibodies in an
      efficient and accurate manner remains a significant issue. It requires numerous
      immunological and functional tests, burdening the laboratory departments, and as
      a consequence, not sufficiently performed in many cases. We retrospectively
      studied a total of 212 subjects with or without collagen diseases including APS
      that visited the outpatients of multiple institutions (department of internal
      medicine at Health Science University of Hokkaido, department of medicine II and
      department of gastroenterology at Hokkaido University Hospital). All the subjects
      were measured aPL (anticardio anticardiolipin antibody IgG/IgM, anti-beta2
      glycoprotein I antibody IgG/IgM) using a fully automated chemiluminescence
      analyzer and compared measurement results with those obtained using the
      conventional ELISA method. These methods were found to have similar diagnostic
      accuracy, with kappa values exceeding 0.6. Of 61 APS patients 41 (67%) were
      positive for two or more tests: significantly higher than other disease such as
      systemic lupus erythematosus (3/37, 9%) or non-SLE collagen disease (1/53, 2%).
      The fully automated chemiluminescence analyzer, which can simultaneously measure
      multiple aPLs, was thus determined to be useful for diagnosing APS.

PMID- 26213195
TI  - A case of lacrimal sarcoidosis following interstitial pneumonia: imaging and
      management.
AB  - A 60-year-old Japanese man developed a fever and dry cough. Although chest CT
      showed interstitial pneumonia, the primary disease was not revealed. The
      interstitial pneumonia was improved by treatment with oral prednisolone following
      methylprednisolone pulse therapy. After the discontinuation of prednisolone he
      developed swelling of the eyelids and polyarthralgia. Orbital magnetic resonance
      imaging showed enlargement of the bilateral lacrimal glands. (67)Gallium
      scintigraphy showed abnormal uptake of the bilateral lacrimal glands and
      pulmonary hilum. A lacrimal gland biopsy showed noncaseating granulomatous
      infiltration with occasional multinucleated giant cells consistent with
      sarcoidosis. His symptoms improved by treatment with oral prednisolone and
      triamcinolone injection into the lacrimal glands.

PMID- 26213196
TI  - Light-Driven Proton Reduction in Aqueous Medium Catalyzed by a Family of Cobalt
      Complexes with Tetradentate Polypyridine-Type Ligands.
AB  - A series of tetradentate 2,2':6',2":6",2'''-quaterpyridine-type ligands related
      to ppq (ppq = 8-(1",10"-phenanthrol-2"-yl)-2-(pyrid-2'-yl)quinoline) have been
      synthesized. One ligand replaces the 1,10-phenanthroline (phen) moiety of ppq
      with 2,2'-bipyridine and the other two ligands have a 3,3'-polymethylene subunit
      bridging the quinoline and pyridine. The structural result is that both the
      planarity and flexibility of the ligand are modified. Co(II) complexes are
      prepared and characterized by ultraviolet-visible light (UV-vis) and mass
      spectroscopy, cyclic voltammetry, and X-ray analysis. The light-driven H2
      evolving activity of these Co complexes was evaluated under homogeneous aqueous
      conditions using [Ru(bpy)3](2+) as the photosensitizer, ascorbic acid as a
      sacrificial electron donor, and a blue light-emitting diode (LED) as the light
      source. At pH 4.5, all three complexes plus [Co(ppq)Cl2] showed the fastest rate,
      with the dimethylene-bridged system giving the highest turnover frequency (2125
      h(-1)). Cyclic voltammograms showed a significant catalytic current for H2
      production in both aqueous buffer and H2O/DMF medium. Combined experimental and
      theoretical study suggest a formal Co(II)-hydride species as a key intermediate
      that triggers H2 generation. Spin density analysis shows involvement of the
      tetradentate ligand in the redox sequence from the initial Co(II) state to the
      Co(II)-hydride intermediate. How the ligand scaffold influences the catalytic
      activity and stability of catalysts is discussed, in terms of the rigidity and
      differences in conjugation for this series of ligands. 

PMID- 26213197
TI  - Psychological effects of (non)employment: A cross-national comparison of the
      United States and Japan.
AB  - The involuntary loss of employment has been shown to deteriorate subjective well
      being. Adopting a cross-cultural perspective on Jahoda's (1982) deprivation model
      this study examines several latent and manifest benefits of work that were
      expected to mediate the effects of employment status on well-being. It was
      hypothesized that in more collectivistic societies the decline in subjective well
      being would be a consequence of a diminished sense of collective purpose for the
      non-employed, whereas in individualistic societies the crucial factors would be a
      loss of social status and financial benefits. The findings from two
      representative national surveys conducted in the United States (N = 1,093) and
      Japan (N = 647) provided partial support for these hypotheses. Cultural
      differences moderated the effects of employment status on the benefits of work.
      As a consequence, different processes mediated the decline in well-being for the
      non-employed in the two countries. These results are embedded within the wider
      discourse on culture and its effect on unemployment.

PMID- 26213198
TI  - Management of Acute Postoperative Pain in Hand Surgery: A Systematic Review.
AB  - PURPOSE: To conduct a systematic review to guide hand surgeons in an evidenced
      based approach in managing postoperative pain. METHODS: We performed a literature
      review for primary research articles on management of postoperative pain in hand
      surgery patients using Medical Literature Analysis and Retrieval System Online
      (MEDLINE; PubMed), Excerpta Medica database (EMBASE), and the Cochrane
      Collaboration Library. Inclusion criteria were primary journal articles examining
      treatment of acute postoperative pain based on any modality. Data related to pain
      assessment, postoperative recovery, and total postoperative analgesic consumption
      were extracted. RESULTS: A total of 903 publications were reviewed; 184
      publications underwent abstract review. After applying inclusion and exclusion
      criteria, 10 primary articles were selected for inclusion in this review. Data
      were noted to be heterogeneous and findings were compiled. Results were divided
      into groups evaluating postoperative pain medications or pain infusion catheters.
      CONCLUSIONS: Although this review did not demonstrate a best practices model for
      postoperative pain management, it provides evidence for alternative medications
      and treatment strategies. The evidence available suggests that postoperative pain
      control should begin before surgery and that combining multiple strategies for
      pain treatment is beneficial. Given the increasing attention paid to narcotic
      prescriptions and the potential for abuse, surgeons should adopt evidence-based
      pain management practices. We provide an example algorithm for pain treatment in
      hand surgery based on available data and the authors' experience. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic III.

PMID- 26213199
TI  - Intraneural Ganglions of the Hand and Wrist.
AB  - PURPOSE: To review 15 patients who were treated for intraneural ganglions of the
      hand and wrist. METHODS: Between 1990 and 2012, 15 patients were treated for
      intraneural ganglions of the hand and wrist. There were 9 women and 6 men,
      averaged age 42 years. Ten patients presented with a mass and 5 with symptoms of
      entrapment neuropathy. The ganglions involved the ulnar nerve at the wrist in 5
      patients, the dorsal branch of the ulnar nerve in 2, the superficial radial nerve
      in 2, a digital nerve in 4, and the dorsal branch of a digital nerve in 2. Eight
      patients had magnetic resonance imaging evaluations that showed cystic masses
      that did not confirm intraneural ganglions. In all patients diagnosis was made
      intraoperatively. Ganglions were treated by intraneural dissection and excision
      of the cyst in 10 patients, excision of the articular branch and decompression of
      the cyst in 4, and excision of the ganglion and the nerve in 1. RESULTS:
      Postoperative follow-up averaged 57 months. There were no complications or
      recurrences. Five patients had transient paresthesias that improved after an
      average of 2 months. Preoperative symptoms improved in all patients. Patients
      returned to normal daily and work activities at an average of 10 days.
      CONCLUSIONS: Intraneural ganglions should be considered in the differential
      diagnosis of a mass in the vicinity of a nerve. Surgical excision is usually
      curative but simple excision of the articular branch and decompression of the
      cyst seems simpler and equally effective. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 26213200
TI  - A Comparative Study of Attitudes Regarding Digit Replantation in the United
      States and Japan.
AB  - PURPOSE: To compare the societal preferences for finger replantation between the
      United States (US) and Japan and to investigate factors influencing the
      preferences. METHODS: A sample of the general population without current hand
      disease or condition was recruited via flyers posted in public areas of 2 major
      academic centers in the US and Japan. The recruited subjects completed a survey
      presenting finger amputation scenarios and various factors that may affect
      treatment decisions. We performed univariate analysis using treatment preference
      as the outcome and all other factors as possible predictors using the chi-square
      test. RESULTS: Most respondents in both countries preferred replantation and
      there was no significant difference between the US and Japan. Treatment
      preference was significantly associated with the importance of appearance,
      recovery time, and the chance of survival of the replanted digit. There was no
      association between treatment preference and attitudes regarding body integrity
      or estimate of stigma toward finger amputees. Japanese participants agreed more
      with statements of body integrity, and Japanese respondents rated appearance,
      sensation, and chance of survival of the replant as more important than did
      American participants. CONCLUSIONS: Patient preference is not driving the
      decrease in finger replantations in the US. The general public in both countries
      prefer replantation over wound closure for digit amputations. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Economic and decision analysis III.

PMID- 26213201
TI  - Paul R. Manske 2014 Award for the Best Upper Extremity Congenital Research
      Manuscript.

PMID- 26213202
TI  - Response to "Reattachment of Flexor Digitorum Profundus Avulsion: Biomechanical
      Performance of 3 Techniques".

PMID- 26213204
TI  - The ferrocene effect: enhanced electrocatalytic hydrogen production using meso
      tetraferrocenyl porphyrin palladium(II) and copper(II) complexes.
AB  - Copper(ii) and palladium(ii) meso-tetraferrocenylporphyrins ( and ) were employed
      as catalysts for electrochemical proton reduction in DMF using trifluoroacetic
      acid (TFA) or triethylamine hydrochloride (TEAHCl) as acids. Gas analysis under
      electrocatalytic conditions at a glassy carbon working electrode confirmed the
      product as H2. showed catalytic behavior for both TFA and TEAHCl, whereas only
      TFA worked for . The performance of the two compounds for electrocatalytic
      hydrogen generation was compared to the analogous copper(ii) and palladium(ii)
      meso-tetraphenylporphyrins ( and ) under identical conditions. The presence of
      the ferrocence groups on the porphyrin favourably shift the overpotential to a
      less negative value by around 200 mV and increases the catalytic rate of hydrogen
      production in DMF/TFA by an order of magnitude to 6 * 10(3) s(-1). Moreover,
      while is fully inactive in a DMF/TEAHCl mixture, the ferrocene subunits activate
      the catalyst. Spectroelectrochemistry experiments and DFT calculations were
      consistent with a catalytic process proceeding via the phlorin anion. 

PMID- 26213203
TI  - Expression of a ULK1/2 binding-deficient ATG13 variant can partially restore
      autophagic activity in ATG13-deficient cells.
AB  - Autophagy describes an intracellular process responsible for the lysosome
      dependent degradation of cytosolic components. The ULK1/2 complex comprising the
      kinase ULK1/2 and the accessory proteins ATG13, RB1CC1, and ATG101 has been
      identified as a central player in the autophagy network, and it represents the
      main entry point for autophagy-regulating kinases such as MTOR and AMPK. It is
      generally accepted that the ULK1 complex is constitutively assembled independent
      of nutrient supply. Here we report the characterization of the ATG13 region
      required for the binding of ULK1/2. This binding site is established by an
      extremely short peptide motif at the C terminus of ATG13. This motif is mandatory
      for the recruitment of ULK1 into the autophagy-initiating high-molecular mass
      complex. Expression of a ULK1/2 binding-deficient ATG13 variant in ATG13
      deficient cells resulted in diminished but not completely abolished autophagic
      activity. Collectively, we propose that autophagy can be executed by mechanisms
      that are dependent or independent of the ULK1/2-ATG13 interaction. 

PMID- 26213205
TI  - Simulation of 3D tumor cell growth using nonlinear finite element method.
AB  - We propose a novel parallel computing framework for a nonlinear finite element
      method (FEM)-based cell model and apply it to simulate avascular tumor growth. We
      derive computation formulas to simplify the simulation and design the basic
      algorithms. With the increment of the proliferation generations of tumor cells,
      the FEM elements may become larger and more distorted. Then, we describe a remesh
      and refinement processing of the distorted or over large finite elements and the
      parallel implementation based on Message Passing Interface to improve the
      accuracy and efficiency of the simulation. We demonstrate the feasibility and
      effectiveness of the FEM model and the parallelization methods in simulations of
      early tumor growth. 

PMID- 26213206
TI  - A peculiar lamin in a peculiar mammal: Expression of lamin LIII in platypus
      (Ornithorhynchus anatinus).
AB  - Platypus (Ornithorhynchus anatinus) holds a unique phylogenetic position at the
      base of the mammalian lineage due to an amalgamation of mammalian and sauropsid
      like features. Here we describe the set of four lamin genes for platypus. Lamins
      are major components of the nuclear lamina, which constitutes a main component of
      the nucleoskeleton and is involved in a wide range of nuclear functions.
      Vertebrate evolution was accompanied by an increase in the number of lamin genes
      from a single gene in their closest relatives, the tunicates and
      cephalochordates, to four genes in the vertebrate lineage. Of the four genes the
      LIII gene is characterized by the presence of two alternatively spliced CaaX
      encoding exons. In amphibians and fish LIII is the major lamin protein in oocytes
      and early embryos. The LIII gene is conserved throughout the vertebrate lineage,
      with the notable exception of marsupials and placental mammals, which have lost
      the LIII gene. Here we show that platypus has retained an LIII gene, albeit with
      a significantly altered structure and with a radically different expression
      pattern. The platypus LIII gene contains only a single CaaX-encoding exon and the
      head domain together with coil 1a and part of coil1b of the platypus LIII protein
      is replaced by a novel short non-helical N-terminus. It is expressed exclusively
      in the testis. These features resemble those of male germ cell-specific lamins in
      placental mammals, in particular those of lamin C2. Our data suggest (i) that the
      specific functions of LIII, which it fulfills in all other vertebrates, is no
      longer required in mammals and (ii) once it had been freed from these functions
      has undergone structural alterations and has adopted a new functionality in
      monotremes. 

PMID- 26213207
TI  - A new QM/MM method oriented to the study of ionic liquids.
AB  - The interest on room temperature ionic liquids has grown in the last decades
      because of their use as all-purpose solvent and their low environmental impact.
      In the present work, a new theoretical procedure is developed to study pure ionic
      liquids within the framework of the quantum mechanics/molecular mechanics method.
      Each type of ion (cation or anion) is considered as an independent entity quantum
      mechanically described that follows a differentiated path in the liquid. The
      method permits, through an iterative procedure, the full coupling between the
      polarized charge distribution of the ions and the liquid structure around them.
      The procedure has been tested with 1-ethyl-3-methylimidazolium tetrafluoroborate.
      It was found that, similar to non-polar liquids and as a consequence of the low
      value of the reaction field, the cation and anion charge distributions are hardly
      polarized by the rest of molecules in the liquid. Their structure is
      characterized by an alternance between anion and cation shells as evidenced by
      the coincidence of the first maximum of the anion-anion and cation-cation radial
      distribution functions with the first minimum of the anion-cation. Some degree of
      stacking between the cations is also found.

PMID- 26213208
TI  - Investigation of pH Influence on Skin Permeation Behavior of Weak Acids Using
      Nonsteroidal Anti-Inflammatory Drugs.
AB  - As a continuing effort to understand the skin permeation behavior of weak acids
      and bases, the objectives of the present study were to evaluate skin permeation
      of nonsteroidal anti-inflammatory drugs (NSAIDs) under the influence of pH,
      investigate the mechanism of pH effect, and examine a previous hypothesis that
      the effective skin pH for drug permeation is different from donor solution pH. In
      vitro permeability experiments were performed in side-by-side diffusion cells
      with diclofenac, ibuprofen, flurbiprofen, ketoprofen, and naproxen and human
      skin. The donor solution pH significantly affected skin permeation of NSAIDs,
      whereas no effect of the receiver pH was observed. Similar to previous
      observations, the apparent permeability coefficient versus donor solution pH
      relationships deviated from the predictions (fractions of unionized NSAIDs)
      according to the acid/base theory. The influences of the viable epidermis
      barrier, polar pathway transport, ion permeation across skin, and effective skin
      pH were investigated. The effective pH values for skin permeation determined
      using the NSAIDs (weak acids) in this study were different from those obtained
      previously with a weak base at the same donor solution pH conditions, suggesting
      that the observed permeability-pH relationships could not be explained solely by
      possible pH differences between skin and donor solution.

PMID- 26213209
TI  - Utility of current sialendoscopes in the sinonasal cavity.
AB  - OBJECTIVES: This study assessed the utility of current sialendoscopes in the
      paranasal sinuses in a cadaveric model and evaluated novel uses for
      sialendoscopes. METHODS: Currently available sialendoscopes were used for
      visualisation and performing interventions in the paranasal sinuses. Ten cadaver
      heads were studied before and after dissection. Outcomes included ostia
      identification, sinus cannulation, success of mucosal biopsy collection and image
      clarity. RESULTS: Marchal and Erlangen sialendoscopes were found to be effective
      for both visualising and cannulating the sphenoid sinuses before and after
      dissection. Both types demonstrated poor maxillary ostia visualisation without
      dissection, but did allow treatment after antrostomy. Larger diameter
      sialendoscopes were associated with the lowest image distortion during maxillary
      ostia assessment. Mucosal biopsy collection within the sphenoid sinus, but not in
      the maxillary sinus, was possible before dissection. CONCLUSION: Sialendoscopes
      can be used for visualisation and performing interventions in the sinonasal
      cavity, but their utility is mainly limited to the sphenoid sinus. They may be
      considered a minimally invasive method for drug delivery and/or biopsy collection
      in the post-operative setting for all sinuses. Design improvements are suggested.

PMID- 26213210
TI  - Monocarboxylate transporter 4, associated with the acidification of synovial
      fluid, is a novel therapeutic target for inflammatory arthritis.
AB  - OBJECTIVE: Synovial fluid pH is decreased in patients with rheumatoid arthritis
      (RA); however, the underlying mechanisms are unclear. We undertook this study to
      examine the mechanism by which synovial fluid pH is regulated and to explore the
      possibility of a therapeutic strategy by manipulating this mechanism. METHODS: We
      determined the pH and lactate concentration in synovial fluid from 16 RA
      patients. Cultured synovial fibroblasts (SFs) from the inflamed joints of 9 RA
      patients (RASFs) were examined for the expression of ion transporters that
      regulate intracellular and extracellular pH. The ion transporter up-regulated in
      RASF lines was then suppressed in RASFs by small interfering RNA (siRNA), and the
      effect of transfection on viability and proliferation was investigated. Finally,
      we examined the therapeutic effect of electrotransfer of monocarboxylate
      transporter 4 (MCT4)-specific siRNA into the articular synovium of mice with
      collagen-induced arthritis (CIA). RESULTS: Synovial fluid pH correlated inversely
      with both the Disease Activity Score in 28 joints using the C-reactive protein
      level and the synovial fluid lactate levels. RASFs exhibited up-regulated
      transcription of MCT4 messenger RNA. MCT4 exported intracellular lactate into the
      extracellular space. RASFs had significantly higher MCT4 protein levels than did
      SFs from patients with osteoarthritis. Knockdown of MCT4 induced intrinsic
      apoptosis of RASFs, thereby inhibiting their proliferation. Moreover,
      electrotransfer of MCT4-specific siRNA into the articular synovium of mice with
      CIA significantly reduced the severity of arthritis. CONCLUSION: RA activity
      correlated with decreased synovial fluid pH. This may be due to increased MCT4
      expression in RASFs. Silencing MCT4 induced apoptosis in RASFs and reduced the
      severity of CIA, suggesting that MCT4 is a potential therapeutic target for
      inflammatory arthritis.

PMID- 26213211
TI  - Impact of early disease progression and surgical complications on adjuvant
      chemotherapy completion rates and survival in patients undergoing the surgery
      first approach for resectable pancreatic ductal adenocarcinoma - A population
      based cohort study.
AB  - BACKGROUND: Multimodality treatment (MMT) improves survival for patients with
      pancreatic ductal adenocarcinoma (PDAC). The surgery-first (SF) strategy is the
      most universally accepted approach. MATERIAL AND METHODS: Population-based
      retrospective cohort study of all cases of resectable PDAC from 2006 to 2012.
      Patients were planned for adjuvant chemotherapy (AC) with the Nordic 5
      fluorouracil/leucovorin regimen. Reasons for and rates of failure to complete AC,
      postoperative major complications (PMC), and overall survival (OS) were analysed.
      RESULTS: Of 203 patients, 85 (41.9%) completed AC, 41 (20.2%) failed to complete
      AC, and 77 (37.9%) never initiated AC. Primary reasons for not initiating or
      completing AC were early disease progression (34.7%), postoperative
      complications/poor performance status (32.2%), and age > 75 years (24.6%). Median
      OS in the whole cohort was 17.0 months, and 20.0 months in patients who initiated
      AC. Median OS in patients who completed AC was higher than in patients who did
      not (25.0 months vs. 12.0 months, p < 0.001). PMC (n = 41) were associated with
      decreased initiation rate (p < 0.001) and completion rate (p = 0.007) of AC, and
      decreased median OS (11.0 months vs. 19.0 months, p = 0.028). Among patients with
      R1 resection, PMC again were associated with worse median OS (8.0 months vs. 16.0
      months, p = 0.028). Multivariate analysis demonstrated that completion of MMT and
      tumour grade (G1/G2) were related to mortality rate (p < 0.001). Mortality risk
      for patients who completed AC was reduced also when adjusting for competing risk
      (SHR 0.426, p < 0.001). CONCLUSIONS: MMT completion is strongly associated with
      reduced mortality risk in patients with resectable PDAC undergoing the SF
      approach. Early disease progression and PMC/poor performance status preclude MMT
      completion in more than one third of the patients. These reasons for failure to
      complete MMT underscore the need for strategies to improve patient selection and
      reduce surgical morbidity in patients with resectable PDAC.

PMID- 26213213
TI  - Cell cycle timing regulation during asynchronous divisions of the early C.
      elegans embryo.
AB  - A fundamental question in developmental biology is how different cell lineages
      acquire different cell cycle durations. With its highly stereotypical asymmetric
      and asynchronous cell divisions, the early Caenorhabditis elegans embryo provides
      an ideal system to study lineage-specific cell cycle timing regulation during
      development, with high spatio-temporal resolution. The first embryonic division
      is asymmetric and generates two blastomeres of different sizes (AB>P1) and
      developmental potentials that divide asynchronously, with the anterior somatic
      blastomere AB dividing reproducibly two minutes before the posterior germline
      blastomere P1. The evolutionarily conserved PAR proteins (abnormal embryonic
      PARtitioning of cytoplasm) regulate all of the asymmetries in the early embryo
      including cell cycle asynchrony between AB and P1 blastomeres. Here we discuss
      our current understanding and open questions on the mechanism by which the PAR
      proteins regulate asynchronous cell divisions in the early C. elegans embryo. 

PMID- 26213212
TI  - Identification of methylation markers for the prediction of nodal metastasis in
      oral and oropharyngeal squamous cell carcinoma.
AB  - Hypermethylation is an important mechanism for the dynamic regulation of gene
      expression, necessary for metastasizing tumour cells. Our aim is to identify
      methylation tumour markers that have a predictive value for the presence of
      regional lymph node metastases in patients with oral and oropharyngeal squamous
      cell carcinoma (OOSCC). Significantly differentially expressed genes were
      retrieved from four reported microarray expression profiles comparing pN0 and pN+
      head-neck tumours, and one expression array identifying functionally
      hypermethylated genes. Additional metastasis-associated genes were included from
      the literature. Thus genes were selected that influence the development of nodal
      metastases and might be regulated by methylation. Methylation-specific PCR (MSP)
      primers were designed and tested on 8 head-neck squamous cell carcinoma cell
      lines and technically validated on 10 formalin-fixed paraffin-embedded (FFPE)
      OOSCC cases. Predictive value was assessed in a clinical series of 70 FFPE OOSCC
      with pathologically determined nodal status. Five out of 28 methylation markers
      (OCLN, CDKN2A, MGMT, MLH1 and DAPK1) were frequently differentially methylated in
      OOSCC. Of these, MGMT methylation was associated with pN0 status (P = 0.02) and
      with lower immunoexpression (P = 0.02). DAPK1 methylation was associated with pN+
      status (P = 0.008) but did not associate with protein expression. In conclusion,
      out of 28 candidate genes, two (7%) showed a predictive value for the pN status.
      Both genes, DAPK1 and MGMT, have predictive value for nodal metastasis in a
      clinical group of OOSCC. Therefore DNA methylation markers are capable of
      contributing to diagnosis and treatment selection in OOSCC. To efficiently
      identify additional new methylation markers, genome-wide methods are needed. 

PMID- 26213214
TI  - Differences in Adolescent Substance Use by Hispanic Subgroup: What We Know and
      What We Need to Find out.
AB  - Differences in health outcomes on the basis of racial and/or ethnic group
      membership have been documented among Hispanics in the US. As this heterogeneous
      population continues to grow, so does the importance of understanding the
      subgroups within it and the possible effect that between-group variations may
      have on health outcomes. This article highlights a major limitation of the
      existing research: that the Hispanic population is almost exclusively lumped into
      one pan-ethnic category when examining substance use behaviors. However, there is
      evidence to suggest that differences in substance use behaviors exist between
      Hispanic subgroups, which may be important when designing prevention and
      intervention programs. While the majority of research in this arena has focused
      on adults, more research is required to understand subgroup differences in
      substance use behaviors among Hispanic youth. This article provides a synopsis of
      the research on U.S. Hispanic substance use behaviors, including how factors such
      as acculturation, nativity, and culture of origin can act as risk and protective
      factors. However, there is an insufficient amount of research looking at how the
      differences between Hispanic subgroups may interact with acculturation levels to
      increase or decrease risk factors associated with substance use. Therefore, the
      authors suggest that substance use researchers attempt to improve future study
      designs by asking standardized demographic questions of national origin and/or
      ethnic/subgroup identity and take this into account in their analyses. The
      collection of such specific data could then be used to develop more targeted
      prevention and intervention programs. 

PMID- 26213215
TI  - In vitro analysis of phosphorothioate modification of DNA reveals substrate
      recognition by a multiprotein complex.
AB  - A wide variety of prokaryotes possess DNA modifications consisting of sequence
      specific phosphorothioates (PT) inserted by members of a five-gene cluster.
      Recent genome mapping studies revealed two unusual features of PT modifications:
      short consensus sequences and partial modification of a specific genomic site in
      a population of bacteria. To better understand the mechanism of target selection
      of PT modifications that underlies these features, we characterized the substrate
      recognition of the PT-modifying enzymes termed DptC, D and E in a cell extract
      system from Salmonella. The results revealed that double-stranded
      oligodeoxynucleotides underwent de novo PT modification in vitro, with the same
      modification pattern as in vivo, i. e., GpsAAC/GpsTTC motif. Unexpectedly, in
      these in vitro analyses we observed no significant effect on PT modification by
      sequences flanking GAAC/GTTC motif, while PT also occurred in the GAAC/GTTC motif
      that could not be modified in vivo. Hemi-PT DNA also served as substrate of the
      PT-modifying enzymes, but not single-stranded DNA. The PT-modifying enzymes were
      then found to function as a large protein complex, with all of three subunits in
      tetrameric conformations. This study provided the first demonstration of in vitro
      DNA PT modification by PT-modifying enzymes that function as a large protein
      complex. 

PMID- 26213216
TI  - An unexpected target of spinal direct current stimulation: Interhemispheric
      connectivity in humans.
AB  - BACKGROUND: Transcutaneous spinal Direct Current Stimulation (tsDCS) is a
      noninvasive technique based on the application of weak electrical currents over
      spinal cord. NEW METHOD: We studied the effects of tsDCS on interhemispheric
      motor connectivity and visual processing by evaluating changes in ipsilateral
      Silent Period (iSP), Transcallosal Conduction Time (TCT) and hemifield Visual
      Evoked Potentials (hVEPs), before (T0) and at a different intervals following
      sham, anodal and cathodal tsDCS (T9-T11 level, 2.0 mA, 20'). Motor Evoked
      Potentials (MEPs) were recorded from abductor pollicis brevis (APB), abductor
      hallucis (AH) and deltoid muscles. hVEPs were recorded bilaterally by reversal of
      a horizontal square wave grating with the display positioned in the right
      hemifield. RESULTS: Anodal tsDCS increased TCT (p < 0.001) and the
      interhemispheric delay for both the main VEP components (N1: p = 0.0003; P1: p <
      0.0001), dampening at the same time iSP duration (APB: p < 0.0001; AH: p =
      0.0005; deltoid: p < 0.0001), while cathodal stimulation elicited opposite
      effects (p < 0.0001). DISCUSSION: tsDCS modulates interhemispheric processing in
      a polarity-specific manner, with anodal stimulation leading to a functional
      disconnection between hemispheres. tsDCS would be a new promising therapeutic
      tool in managing a number of human diseases characterized by an impaired
      interhemispheric balance, or an early rehabilitation strategy in patients with
      acute brain lesions, when other non-invasive brain stimulation techniques (NIBS)
      are not indicated due to safety concerns.

PMID- 26213217
TI  - AICHA: An atlas of intrinsic connectivity of homotopic areas.
AB  - BACKGROUND: Atlases of brain anatomical ROIs are widely used for functional MRI
      data analysis. Recently, it was proposed that an atlas of ROIs derived from a
      functional brain parcellation could be advantageous, in particular for
      understanding how different regions share information. However, functional
      atlases so far proposed do not account for a crucial aspect of cerebral
      organization, namely homotopy, i.e. that each region in one hemisphere has a
      homologue in the other hemisphere. NEW METHOD: We present AICHA (for Atlas of
      Intrinsic Connectivity of Homotopic Areas), a functional brain ROIs atlas based
      on resting-state fMRI data acquired in 281 individuals. AICHA ROIs cover the
      whole cerebrum, each having 1-homogeneity of its constituting voxels intrinsic
      activity, and 2-a unique homotopic contralateral counterpart with which it has
      maximal intrinsic connectivity. AICHA was built in 4 steps: (1) estimation of
      resting-state networks (RSNs) using individual resting-state fMRI independent
      components, (2) k-means clustering of voxel-wise group level profiles of
      connectivity, (3) homotopic regional grouping based on maximal inter-hemispheric
      functional correlation, and (4) ROI labeling. RESULTS: AICHA includes 192
      homotopic region pairs (122 gyral, 50 sulcal, and 20 gray nuclei). As an
      application, we report inter-hemispheric (homotopic and heterotopic) and intra
      hemispheric connectivity patterns at different sparsities. COMPARISON WITH
      EXISTING METHOD: ROI functional homogeneity was higher for AICHA than for
      anatomical ROI atlases, but slightly lower than for another functional ROI atlas
      not accounting for homotopy. CONCLUSION: AICHA is ideally suited for
      intrinsic/effective connectivity analyses, as well as for investigating brain
      hemispheric specialization.

PMID- 26213218
TI  - Hypothalamic, thalamic and hippocampal lesions in the mouse MCAO model: Potential
      involvement of deep cerebral arteries?
AB  - Intraluminal monofilament occlusion of the middle cerebral artery (MCAO) in mice
      is the most used rodent model to study the pathophysiology of stroke. However,
      this model often shows brain damage in regions not supplied by the MCA such as
      the hypothalamus, hippocampus and thalamus. Several studies have suggested some
      explanations on these localized infarcts. We aim to provide an alternative
      explanation which could allow each experimenter to better grasp the MCAO model.
      We propose that the MCA occlusion by the monofilament also occludes deep and
      small cerebral arteries arising directly from the internal carotid artery,
      proximally to the origin of MCA. Then, drawbacks and pitfalls of the MCAO model
      must be appreciated and the almost systematic risk of inducing lesions in some
      unwanted territories for neuroanatomical reasons, i.e. vascular connections
      between deep arteries and hypothalamic, thalamic and hippocampal areas in rodents
      has to be integrated. 

PMID- 26213219
TI  - Methods of automated absence seizure detection, interference by stimulation, and
      possibilities for prediction in genetic absence models.
AB  - BACKGROUND: Genetic rat models for childhood absence epilepsy have become
      instrumental in developing theories on the origin of absence epilepsy, the
      evaluation of new and experimental treatments, as well as in developing new
      methods for automatic seizure detection, prediction, and/or interference of
      seizures. METHOD: Various methods for automated off and on-line analyses of ECoG
      in rodent models are reviewed, as well as data on how to interfere with the spike
      wave discharges by different types of invasive and non-invasive electrical,
      magnetic, and optical brain stimulation. Also a new method for seizure prediction
      is proposed. RESULTS: Many selective and specific methods for off- and on-line
      spike-wave discharge detection seem excellent, with possibilities to overcome the
      issue of individual differences. Moreover, electrical deep brain stimulation is
      rather effective in interrupting ongoing spike-wave discharges with low
      stimulation intensity. A network based method is proposed for absence seizures
      prediction with a high sensitivity but a low selectivity. Solutions that prevent
      false alarms, integrated in a closed loop brain stimulation system open the ways
      for experimental seizure control. CONCLUSIONS: The presence of preictal cursor
      activity detected with state of the art time frequency and network analyses shows
      that spike-wave discharges are not caused by sudden and abrupt transitions but
      that there are detectable dynamic events. Their changes in time-space-frequency
      characteristics might yield new options for seizure prediction and seizure
      control.

PMID- 26213220
TI  - Time-frequency analysis of resting state and evoked EEG data recorded at higher
      magnetic fields up to 9.4 T.
AB  - BACKGROUND: Combining both high temporal and spatial resolution by means of
      simultaneous electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI) is of relevance to neuroscientists. This combination, however,
      leads to a distortion of the EEG signal by the so-called cardio-ballistic
      artefacts. The aim of the present study was developing an approach to restore
      meaningful physiological EEG data from recordings at different magnetic fields.
      NEW METHODS: The distortions introduced by the magnetic field were corrected
      using a combination of concepts from independent component analysis (ICA) and
      mutual information (MI). Thus, the components were classified as either related
      to the cardio-ballistic artefacts or to the signals of interest. EEG data from
      two experimental paradigms recorded at different magnetic field strengths up to
      9.4 T were analyzed: (i) spontaneous activity using an eyes-open/eyes-closed
      alternation, and (ii) responses to auditory stimuli, i.e. auditory evoked
      potentials. RESULTS: Even at ultra-high magnetic fields up to 9.4 T the proposed
      artefact rejection approach restored the physiological time-frequency information
      contained in the signal of interest and the data were suitable for subsequent
      analyses. COMPARISON WITH EXISTING METHODS: Blind source separation (BSS) has
      been used to retrieve information from EEG data recorded inside the MR scanner in
      previous studies. After applying the presented method on EEG data recorded at 4
      T, 7 T, and 9.4 T, we could retrieve more information than from data cleaned with
      the BSS method. CONCLUSIONS: The present work demonstrates that EEG data recorded
      at ultra-high magnetic fields can be used for studying neuroscientific research
      question related to oscillatory activity.

PMID- 26213221
TI  - Family peer support work in an early intervention youth mental health service.
AB  - This paper describes the evolution of a family peer support programme in an early
      intervention service in Melbourne, Australia. In response to policy directions
      from Federal and State governments calling for carer participation in public
      mental health services, and feedback from the families of young people at Orygen
      Youth Health, the 'Families Helping Families' project was developed. The positive
      acceptance by families of this innovative programme also warrants further
      exploration. The programme has overcome many organizational hurdles associated
      with specifically trained and employed family carers working alongside
      professional mental health clinicians. This article describes the change
      processes involved in implementing this programme and documents preliminary
      expressions of the benefits of family peer support. The contribution of lived
      experience in treatment and consumer care plans needs rigorous research and
      evaluation.

PMID- 26213222
TI  - Partitioning in aqueous two-phase systems: Analysis of strengths, weaknesses,
      opportunities and threats.
AB  - For half a century aqueous two-phase systems (ATPSs) have been applied for the
      extraction and purification of biomolecules. In spite of their simplicity,
      selectivity, and relatively low cost they have not been significantly employed
      for industrial scale bioprocessing. Recently their ability to be readily scaled
      and interface easily in single-use, flexible biomanufacturing has led to
      industrial re-evaluation of ATPSs. The purpose of this review is to perform a
      SWOT analysis that includes a discussion of: (i) strengths of ATPS partitioning
      as an effective and simple platform for biomolecule purification; (ii) weaknesses
      of ATPS partitioning in regard to intrinsic problems and possible solutions;
      (iii) opportunities related to biotechnological challenges that ATPS partitioning
      may solve; and (iv) threats related to alternative techniques that may compete
      with ATPS in performance, economic benefits, scale up and reliability. This
      approach provides insight into the current status of ATPS as a bioprocessing
      technique and it can be concluded that most of the perceived weakness towards
      industrial implementation have now been largely overcome, thus paving the way for
      opportunities in fermentation feed clarification, integration in multi-stage
      operations and in single-step purification processes. 

PMID- 26213223
TI  - Maternal and perinatal outcomes in women planning vaginal birth after caesarean
      (VBAC) at home in England: secondary analysis of the Birthplace national
      prospective cohort study.
AB  - OBJECTIVE: To compare vaginal birth rates in women planning vaginal birth after
      caesarean (VBAC) at home versus in an obstetric unit (OU) and explore transfer
      rates in women planning home VBAC. DESIGN: Prospective cohort study. SETTING: OUs
      and planned home births in England. POPULATION: 1436 women planning VBAC in the
      Birthplace cohort, including 209 planning home VBAC. METHODS: We used Poisson
      regression to calculate relative risks adjusted for maternal characteristics.
      MAIN OUTCOME MEASURES:  MAIN OUTCOMES: (i) vaginal birth and (ii) transfer from
      planned home birth to OU during labour or immediately after birth. SECONDARY
      OUTCOMES: (i) composite of maternal blood transfusion or admission to higher
      level care, (ii) stillbirth or Apgar score <7 at 5 minutes, (iii) neonatal unit
      admission. RESULTS: Planned VBAC at home was associated with a statistically
      significant increase in the chances of having a vaginal birth compared with
      planned VBAC in an OU (adjusted relative risk 1.15, 95% confidence interval 1.06
      1.24). The risk of an adverse maternal outcome was around 2-3% in both settings,
      with a similar risk of an adverse neonatal outcome. Transfer rates were high
      (37%) and varied markedly by parity (para 1, 56.7% versus para 2+, 24.6%).
      CONCLUSION: Women in the cohort who planned VBAC at home had an increased chance
      of a vaginal birth compared with those planning VBAC in an OU, but transfer rates
      were high, particularly for women with only one previous birth, and the risk of
      an adverse maternal or perinatal outcome was around 2-3%. No change in guidance
      can be recommended. TWEETABLE ABSTRACT: Higher vaginal birth rates in planned
      VBAC at home versus in OU but 2-3% adverse outcomes and high transfer rate.

PMID- 26213224
TI  - A Home-Based Palliative Care Consult Service for Veterans.
AB  - We describe the development and implementation of a home-based palliative care
      consult service for Veterans with advanced illness. A retrospective chart review
      was performed on 73 Veterans who received a home-based palliative care consult.
      Nearly one-third were 80 years of age or older, and nearly one-third had a
      palliative diagnosis of cancer. The most common interventions of the consult team
      included discussion of advance directives, completion of a "do not resuscitate"
      form, reduction/stoppage of at least 1 medication, explanation of diagnosis,
      referral to home-based primary care program, referral to hospice, and
      assessment/support for caregiver stress. The home-based consult service was
      therefore able to address clinical and psychosocial issues that can demonstrate a
      direct benefit to Veterans, families, and referring clinicians.

PMID- 26213225
TI  - A Systematic Review of Family Meeting Tools in Palliative and Intensive Care
      Settings.
AB  - PURPOSE: Family meetings can be challenging, requiring a range of skills and
      participation. We sought to identify tools available to aid the conduct of family
      meetings in palliative, hospice, and intensive care unit settings. METHODS: We
      systematically reviewed PubMed for articles describing family meeting tools and
      abstracted information on tool type, usage, and content. RESULTS: We identified
      16 articles containing 23 tools in 7 categories: meeting guide (n = 8), meeting
      planner (n = 5), documentation template (n = 4), meeting strategies (n = 2),
      decision aid/screener (n = 2), family checklist (n = 1), and training module (n =
      1). We found considerable variation across tools in usage and content and a lack
      of tools supporting family engagement. CONCLUSION: There is need to standardize
      family meeting tools and develop tools to help family members effectively engage
      in the process.

PMID- 26213227
TI  - Troponin-like regulation in muscle thin filaments of the mussel Crenomytilus
      grayanus (Bivalvia: Mytiloida).
AB  - Muscles of bivalve molluscs have double calcium regulation--myosin-linked and
      actin-linked. While the mechanism of myosin-linked regulation is sufficiently
      studied, there is still no consensus on the mechanism of actin-linked regulation.
      Earlier we showed a high degree of Ca2+-sensitivity of thin filaments from the
      adductor muscle of the mussel Crenomytilus grayanus (Mytiloida). In order to
      elucidate the nature of this regulation, we isolated the fraction of minor
      proteins from the mussel thin filaments, which confers Ca2+-sensitivity to
      reconstituted actomyosin-tropomyosin. Proteins of this fraction, ABP-19, ABP-20,
      and ABP-28, were chromatographically purified and identified. According to the
      results of mass spectrometry and Western blot analysis, as well as by their
      functional properties, these mussel actin-binding proteins appeared to correspond
      to the troponin components from the skeletal muscles of vertebrates (TnC, TnI and
      TnT). The reconstituted mussel troponin complex confers to actomyosin-tropomyosin
      more than 80% Ca2+-sensitivity. The in vivo molar ratio of
      actin/tropomyosin/troponin was calculated to be 7:1:0.5, i.e., the content of
      troponin in mussel thin filaments is two times lower than in thin filaments of
      skeletal muscles of vertebrates. These data demonstrate that troponin-like
      regulation found in the catch muscle of the mussel C. grayanus is present at
      least in two suborders of bivalves: Pectinoida and Mytiloida.

PMID- 26213226
TI  - Progressive inflammatory pathology in the retina of aluminum-fed 5xFAD transgenic
      mice.
AB  - At least 57 murine transgenic models for Alzheimer's disease (Tg-AD) have been
      developed to overexpress the 42 amino acid amyloid-beta (Abeta42) peptide in the
      central nervous system (CNS). These 'humanized murine Tg-AD models' have greatly
      expanded our understanding of the contribution of Abeta42 peptide-mediated pro
      inflammatory neuropathology to the AD process. A number of independent
      laboratories using different amyloid-overexpressing Tg-AD models have shown that
      supplementation of murine Tg-AD diets and/or drinking water with aluminum
      significantly enhances Abeta42 peptide-mediated inflammatory pathology and AD
      type cognitive change compared to animals receiving control diets. In humans AD
      type pathology appears to originate in the limbic system and progressively
      spreads into primary processing and sensory regions such as the retina. In these
      studies, for the first time, we assess the propagation of Abeta42 and
      inflammatory signals into the retina of 5xFAD Tg-AD amyloid-overexpressing mice
      whose diets were supplemented with aluminum. The two most interesting findings
      were (1) that similar to other Tg-AD models, there was a significantly
      accelerated development of Abeta42 and inflammatory pathology in 5xFAD Tg-AD mice
      fed aluminum; and (2) in aluminum-supplemented animals, markers for inflammatory
      pathology appeared in both the brain and the retina as evidenced by an evolving
      presence of Abeta42 peptides, and accompanied by inflammatory markers -
      cyclooxygenase-2 (COX-2) and C-reactive protein (CRP). The results indicate that
      in the 5xFAD Tg-AD model aluminum not only enhances an Abeta42-mediated
      inflammatory degeneration of the brain but also appears to induce AD-type
      pathology in an anatomically-linked primary sensory area that involves vision. 

PMID- 26213228
TI  - Tridentate Lewis Acids Based on 1,3,5-Trisilacyclohexane Backbones and an Example
      of Their Host-Guest Chemistry.
AB  - Directed tridentate Lewis acids based on the 1,3,5-trisilacyclohexane skeleton
      with three ethynyl groups [CH2Si(Me)(C2H)]3 were synthesised and functionalised
      by hydroboration with HB(C6F5)2, yielding the ethenylborane
      {CH2Si(Me)[C2H2B(C6F5)2]}3, and by metalation with gallium and indium organyls
      affording {CH2Si(Me)[C2M(R)2]}3 (M = Ga, In, R = Me, Et). In the synthesis of the
      backbone the influence of substituents (MeO, EtO and iPrO groups at Si) on the
      orientation of the methyl group was studied with the aim to increase the
      abundance of the all-cis isomer. New compounds were identified by elemental
      analyses, multi-nuclear NMR spectroscopy and in some cases by IR spectroscopy.
      Crystal structures were obtained for cis-trans-[CH2Si(Me)(Cl)]3, all-cis
      [CH2Si(Me)(H)]3, all-cis-[CH2Si(Me)(C2H)]3, cis-trans-[CH2Si(Me)(C2H)]3 and all
      cis-[CH2Si(Me)(C2SiMe3)]3. A gas-phase electron diffraction experiment for all
      cis-[CH2Si(Me)(C2H)]3 provides information on the relative stabilities of the all
      equatorial and all-axial form; the first is preferred in both solid and gas
      phase. The gallium-based Lewis acid {CH2Si(Me)[C2Ga(Et)2]}3 was reacted with a
      tridentate Lewis base (1,3,5-trimethyl-1,3,5-triazacyclohexane) in an NMR
      titration experiment. The generated host-guest complexes involved in the
      equilibria during this reaction were identified by DOSY NMR spectroscopy by
      comparing measured diffusion coefficients with those of the suitable reference
      compounds of same size and shape.

PMID- 26213229
TI  - Identification of osteoblast stimulating factor 5 as a negative regulator in the
      B-lymphopoietic niche.
AB  - Recent studies have revealed the crucial role of the niche which supports B
      lymphocyte differentiation from hematopoietic stem cells. In this study, we aimed
      to identify a novel regulator of B lymphopoiesis secreted in the specific niche
      using the signal sequence trap method. Among the identified proteins from MS5
      stromal cells, expression of pleiotrophin, placental proliferin 2, and osteoblast
      stimulating factor 5 (OSF-5) was dominantly high in several stromal cell lines.
      We found that OSF-5 suppressed early B lymphopoiesis in transgenic mice producing
      the target protein. The number of pre-B and immature B cells was reduced by more
      than half compared with control in the transgenic mice. In vitro studies showed
      that a secreted variant of OSF-5 inhibited the proliferation and colony formation
      of pre-B cells, whereas cell-intrinsic form had no influence on B lymphopoiesis.
      The main components of the B-lymphopoietic niche, osteoblasts in mice and
      mesenchymal cells in humans, are primary producers of OSF-5. These results define
      a novel mechanism of B lymphopoiesis in bone marrow. In the specific niche, B
      lymphocyte differentiation is fine-tuned by negative regulators as well as
      supportive factors. 

PMID- 26213232
TI  - Emphysema: coiling up the lungs, trick or treat?
AB  - Lung volume reduction coil (LVRC) treatment is a minimally-invasive technique
      planned to achieve an improvement of exercise capacity and pulmonary function in
      subjects with advanced emphysema and hyperinflation. It has been proposed
      together with other bronchoscopic lung volume reduction approaches to reduce lung
      hyperinflation in emphysema as less invasive alternatives to LVRS and are
      currently under clinical investigation. Following the successful early
      experiences in previous pilot trials, recent studies allow further investigation
      into the feasibility, safety and efficacy of LVR coil treatment in a multi-center
      setting in a larger group of patients. According to this studies we can state
      that LVR coil treatment results in significant clinical improvements in patients
      with severe emphysema, in multicenter analysis, with a good safety profile and
      sustained results for up to 1 year. The literature on endobronchial coils
      continues to look promising with an acceptable safety profile, and positive long
      term follow-up data are certainly more and more available. However, further well
      designed, blinded, placebo (or sham) controlled trials, and even randomized
      trials against LVRS (lung volume reduction surgery), are needed before routine
      clinical use can be recommended. This is true not only for endobronchial coils,
      but also for the whole field of bronchoscopic lung volume reduction.

PMID- 26213230
TI  - The tissue inhibitor of metalloproteinases 1 increases the clonogenic efficiency
      of human hematopoietic progenitor cells through CD63/PI3K/Akt signaling.
AB  - Initially described as an endogenous inhibitor of proteases, the tissue inhibitor
      of metalloproteinases 1 (TIMP-1) also displays cytokine-like functions. TIMP-1 is
      a soluble protein whose levels are increased under inflammatory conditions. We
      recently found that TIMP-1(-/-) mice have decreased bone marrow (BM) cellularity
      and that the engraftment capability of TIMP-1(-/-) hematopoietic stem cells
      (HSCs) is impaired, owing to proliferation defects. Here, we investigated the
      role of recombinant human TIMP-1 (rhTIMP-1) in human hematopoietic
      stem/progenitor cells (HSPCs) and elucidated the downstream pathway ignited by
      rhTIMP-1. We found that rhTIMP-1 affects in vitro cell survival, proliferation,
      and particularly clonogenic expansion of CD34(+) HSPCs without compromising their
      short-term engraftment potential after transplantation into immunodeficient mice.
      These effects are independent on matrix metalloproteinase (MMP) inhibition and
      rely on TIMP-1's binding to the tetraspanin membrane receptor CD63. Further
      investigation indicated that rhTIMP-1 stimulation induces phosphatidylinositol 3
      kinase (PI3K) recruitment and Akt phosphorylation, both presiding over
      survival/proliferation pathways in HSPCs. Downstream targets of phosphorylated
      Akt (pAkt) are also modulated, including the proliferation marker cyclin D1
      (CycD1), whose levels are increased upon exposure to rhTIMP-1. These findings
      indicate that rhTIMP-1 promotes clonogenic expansion and survival in human
      progenitors via the activation of the CD63/PI3K/pAkt signaling pathway,
      suggesting that TIMP-1 might be a key player in the network of proinflammatory
      factors modulating HSPC functions. 

PMID- 26213233
TI  - Idiopathic pulmonary fibrosis landscapes: looking glass from pathology to
      therapy.
AB  - Idiopathic pulmonary fibrosis (IPF) is a rare chronic and ultimately fatal
      disease resulting in an aberrant scarring and thickening of lung tissue.
      Molecular pathogenetic mechanisms of IPF are still unknown and till now no
      effective therapy is known to really improve disease's outcome. A deeper
      understanding of IPF biology is now mandatory to clarify IPF origin in order to
      identify actionable targets. Here we discuss and analyze the data presented by a
      recent paper published by De Pianto et al. on the prestigious respiratory journal
      Thorax. The work is focused on how gene expression analysis can be applied to
      stratify IPF cases based on their risk of disease progression. Moreover they
      tried to match genetic and phenotypic profiles in order to predict therapeutic
      response and patients' prognosis.

PMID- 26213234
TI  - Investigating Alfvenic wave propagation in coronal open-field regions.
AB  - The physical mechanisms behind accelerating solar and stellar winds are a long
      standing astrophysical mystery, although recent breakthroughs have come from
      models invoking the turbulent dissipation of Alfven waves. The existence of
      Alfven waves far from the Sun has been known since the 1970s, and recently the
      presence of ubiquitous Alfvenic waves throughout the solar atmosphere has been
      confirmed. However, the presence of atmospheric Alfvenic waves does not, alone,
      provide sufficient support for wave-based models; the existence of counter
      propagating Alfvenic waves is crucial for the development of turbulence. Here, we
      demonstrate that counter-propagating Alfvenic waves exist in open coronal
      magnetic fields and reveal key observational insights into the details of their
      generation, reflection in the upper atmosphere and outward propagation into the
      solar wind. The results enhance our knowledge of Alfvenic wave propagation in the
      solar atmosphere, providing support and constraints for some of the recent Alfven
      wave turbulence models. 

PMID- 26213235
TI  - Increased glutathione contributes to stress tolerance and global translational
      changes in Arabidopsis.
AB  - Although glutathione is well known for its reactive oxygen species (ROS)
      scavenging function and plays a protective role in biotic stress, its regulatory
      function in abiotic stress still remains to be elucidated. Our previous study
      showed that exogenously applied reduced glutathione (GSH) could improve abiotic
      stress tolerance in Arabidopsis. Here, we report that endogenously increased GSH
      also conferred tolerance to drought and salt stress in Arabidopsis. Moreover,
      both exogenous and endogenous GSH delayed senescence and flowering time.
      Polysomal profiling results showed that global translation was enhanced after GSH
      treatment and by the induced increase of GSH level by salt stress. By performing
      transcriptomic analyses of steady-state and polysome-bound mRNAs in GSH-treated
      plants, we reveal that GSH has a substantial impact on translation. Translational
      changes induced by GSH treatment target numerous hormones and stress signaling
      molecules, which might contribute to the enhanced stress tolerance in GSH-treated
      plants. Our translatome analysis also revealed that abscisic acid (ABA), auxin
      and jasmonic acid (JA) biosynthesis, as well as signaling genes, were activated
      during GSH treatment, which has not been reported in previously published
      transcriptomic data. Together, our data suggest that the increased glutathione
      level results in stress tolerance and global translational changes. 

PMID- 26213236
TI  - Sustained benefit of continuous subcutaneous insulin infusion on glycaemic
      control and hypoglycaemia in adults with Type 1 diabetes.
AB  - AIM: To evaluate the sustainability of the benefits of continuous subcutaneous
      insulin infusion therapy in routine practice in a cohort of adults with diabetes.
      METHODS: The clinical records of all adults starting continuous subcutaneous
      insulin infusion over 12 years at our centre were included in this study.
      Baseline and mean annual HbA(1c) levels were recorded. The frequency of mild-to
      moderate and severe hypoglycaemia and hypoglycaemia awareness were analysed in a
      subgroup. RESULTS: Adequate data were available from 327 patients, of whom 71%
      were female. The patients' mean +/- sd age was 41 +/- 14 years, the mean +/- sd
      (range) follow-up for continuous subcutaneous insulin infusion was 4.3 +/- 2.7 (1
      12) years. The mean +/- sd HbA(1c) concentration fell by 8 +/- 5 mmol/mol (0.7 +/
      0.5%) at year 1 [to 63 +/- 12 mmol/mol from 70 +/- 18 mmol/mol (7.9 +/- 1.1%
      from 8.6 +/- 1.6%); P < 0.0005], sustained to year 5. In patients with initial
      poor control, HbA(1c) dropped by 12 +/- 11 mmol/mol (1.1 +/- 1.0%; P < 0.0005) at
      year 1, sustained to year 6. The percentage of patients with >= 5 mild to
      moderate hypoglycaemic episodes per week fell from 29 to 12% (n = 163; P =
      0.006). In the subgroup (n = 87; follow-up 2.5 +/- mean +/- sd 1.1 years), the
      frequency of severe hypoglycaemia fell from 0.6 +/- 1.7 episodes per patient per
      year to 0.3 +/- 0.9 (P = 0.047). Of 24 patients with impaired awareness of
      hypoglycaemia (Gold score >= 4), the mean +/- sd Gold score improved from 4.9 +/-
      0.9 to 3.8 +/- 1.7 (P = 0.011). Nine people regained awareness. No deterioration
      in HbA(1c) was seen in the hypoglycaemia-prone groups. CONCLUSIONS: The benefits
      of continuous subcutaneous insulin infusion with regard to improving glycaemic
      control and reducing hypoglycaemia frequency, along with improvement in
      hypoglycaemia awareness without deterioration in glycaemic control, can be
      sustained over several years in clinical practice.

PMID- 26213237
TI  - Synthesis and Antiplasmodial Activity of Novel Chloroquine Analogues with Bulky
      Basic Side Chains.
AB  - Chloroquine is commonly used in the treatment and prevention of malaria, but
      Plasmodium falciparum, the main species responsible for malaria-related deaths,
      has developed resistance against this drug. Twenty-seven novel chloroquine (CQ)
      analogues characterized by a side chain terminated with a bulky basic head group,
      i.e., octahydro-2H-quinolizine and 1,2,3,4,5,6-hexahydro-1,5-methano-8H
      pyrido[1,2-a][1,5]diazocin-8-one, were synthesized and tested for activity
      against D-10 (CQ-susceptible) and W-2 (CQ-resistant) strains of P. falciparum.
      Most compounds were found to be active against both strains with nanomolar or sub
      micromolar IC50 values. Eleven compounds were found to be 2.7- to 13.4-fold more
      potent than CQ against the W-2 strain; among them, four cytisine derivatives
      appear to be of particular interest, as they combine high potency with low
      cytotoxicity against two human cell lines (HMEC-1 and HepG2) along with easier
      synthetic accessibility. Replacement of the 4-NH group with a sulfur bridge
      maintained antiplasmodial activity at a lower level, but produced an improvement
      in the resistance factor. These compounds warrant further investigation as
      potential drugs for use in the fight against malaria. 

PMID- 26213239
TI  - Ranking Theory and Conditional Reasoning.
AB  - Ranking theory is a formal epistemology that has been developed in over 600 pages
      in Spohn's recent book The Laws of Belief, which aims to provide a normative
      account of the dynamics of beliefs that presents an alternative to current
      probabilistic approaches. It has long been received in the AI community, but it
      has not yet found application in experimental psychology. The purpose of this
      paper is to derive clear, quantitative predictions by exploiting a parallel
      between ranking theory and a statistical model called logistic regression. This
      approach is illustrated by the development of a model for the conditional
      inference task using Spohn's (2013) ranking theoretic approach to conditionals. 

PMID- 26213240
TI  - Autologous haematopoietic cell transplantation in elderly patients with multiple
      myeloma.
AB  - High-dose chemotherapy with melphalan followed by autologous haematopoietic cell
      transplantation (AHCT) is a standard of care in young patients (<65 years) with
      multiple myeloma. Most myeloma patients, however, are older than 65 years at the
      time of diagnosis, and the findings of numerous single-centre and registry
      studies provide evidence that AHCT can be a feasible and effective treatment
      option in these patients. Nevertheless, AHCT is not generally recommended as
      standard treatment in the elderly, due to the fact that a benefit of AHCT over
      conventional-dose therapy has not been demonstrated by prospective randomized
      trials. Yet, the use of AHCT has increased substantially in older patients in
      recent years, and an increasing number of reports suggest comparable outcomes for
      older and younger patients after AHCT. In this review we summarize the results of
      AHCT for elderly patients with multiple myeloma. 

PMID- 26213241
TI  - Endotoxin-induced acute lung injury in mice is protected by 5,7-dihydroxy-8
      methoxyflavone via inhibition of oxidative stress and HIF-1alpha.
AB  - Up to date, the morbidity and mortality rates of acute lung injury (ALI) still
      rank high among clinical illnesses. Endotoxin, also called lipopolysaccharide
      (LPS), induced sepsis is the major cause for ALI. Beneficial biological effects,
      such as antioxidation, anti-inflammation, and neuroprotection was found to
      express by 5,7-dihydroxy-8-methoxyflavone (DHMF). The purpose of present study
      was to investigate the potential protective effects of DHMF and the possibile
      mechanisms involved in LPS-induced ALI. In our experimental model, ALI was
      induced in mice by intratracheal injection of LPS, and DHMF at various
      concentrations was injected intraperitoneally for 30 min prior to LPS
      administration. Pretreatment with DHMF inhibited not only the histolopatholgical
      changes occurred in lungs but also leukocytes infiltration in LPS-induced ALI.
      Decreased activity of antioxidative enzymes (AOE) such as superoxide dismutase
      (SOD), catalase (CAT), and glutathione peroxidase (GPx) caused by LPS was
      reversed by DHMF. LPS-induced lipid peroxidation HIF-1alpha accumulation, NF
      kappaB phosphorylation, and IkappaBalpha degradation were all inhibited by DHMF.
      In addition, LPS-induced expression of proinflammatory mediators such as TNF
      alpha and IL-1beta were also inhibited by 5,7-dihydroxy-8-methoxyflavone. These
      results suggested that the protective mechanisms of DHMF on endotoxin-induced ALI
      might be via up-regulation of antioxidative enzymes, inhibition of NFkappaB
      phosphorylation, and HIF-1alpha accumulation. (c) 2015 Wiley Periodicals, Inc.
      Environ Toxicol 31: 1700-1709, 2016.

PMID- 26213242
TI  - Cognitive Orientation to (Daily) Occupational Performance intervention leads to
      improvements in impairments, activity and participation in children with
      Developmental Coordination Disorder.
AB  - INTRODUCTION: Children diagnosed with Developmental Coordination Disorder (DCD)
      present with a variety of impairments in fine and gross motor function, which
      impact on their activity and participation in a variety of settings. This
      research aimed to determine if a 10-week group-based Cognitive Orientation to
      Daily Occupational Performance (CO-OP) intervention improved outcome measures
      across the impairment, activity and participation levels of the International
      Classification of Functioning, Disability and Health (ICF) framework. METHODS: In
      this quasi-experimental, pre-post-test, 20 male children aged 8-10 years (x9y1m
      +/- 9 m) with a confirmed diagnosis of DCD participated in either the 10 week
      group intervention based on the CO-OP framework (n = 10) or in a control period
      of regular activity for 10 weeks (n = 10). Outcome measures relating to
      impairment (MABC-2, motor overflow assessment), activity (Handwriting Speed Test)
      and participation [Canadian Occupational Performance Measure, (COPM) and Goal
      Attainment Scale) were measured at weeks 0 and 10 in the intervention group.
      RESULTS: Children who participated in the CO-OP intervention displayed
      improvements in outcome measures for impairment, activity and participation,
      particularly a reduction in severity of motor overflow. Parent and child
      performance and satisfaction ratings on the COPM improved from baseline to week
      10 and all goals were achieved at or above the expected outcome. No significant
      changes were reported for the control group in impairment and activity
      (participation was not measured for this group). CONCLUSION: The strategies
      implemented by children in the CO-OP treatment group, targeted towards
      individualised goal attainment, show that CO-OP, when run in a group environment,
      can lead to improvements across all levels of the ICF. IMPLICATIONS FOR
      REHABILITATION: Development Coordination Disorder is a condition which has
      significant physical, academic and social impacts on a child and can lead to
      activity limitations and participation restrictions. Cognitive Orientation to
      Daily Occupational Performance is an approach which uses cognitive-based
      strategies to improve performance of specific tasks based on child chosen goals.
      The intervention program had a positive effect on self-perceived levels of
      performance which may lead to changes in quality of life. Parents felt the
      intervention enhanced socialisation, peer modelling and encouragement and felt
      that this increased confidence and independence.

PMID- 26213243
TI  - Return to work for severely injured survivors of the Christchurch earthquake:
      influences in the first 2 years.
AB  - PURPOSE: This study looked at the influences on the return to work (RTW) in the
      first 2 years for people severely injured in the 22 February 2011 Christchurch
      earthquake. METHOD: We used a constructivist grounded theory approach using semi
      structured interviews to collect data from 14 people injured in the earthquake.
      RESULTS: Analysis elicited three themes that appeared to influence the process of
      RTW following the Christchurch earthquake. Living the earthquake experience, the
      individual's experiences of the earthquake and how their injury framed their
      expectations; rebuilding normality, the desire of the participants to return to
      life as it was; while dealing with the secondary effects of the earthquake
      includes the earthquake specific effects which were both barriers and
      facilitators to returning to work. CONCLUSION: The consequences of the earthquake
      impacted on experience, process and outcome of RTW for those injured in the
      Christchurch Earthquake. Work and RTW appeared key tools to enhance recovery
      after serious injury following the earthquake. IMPLICATIONS FOR REHABILITATION:
      The altered physical, social and economic environment must be considered when
      working on the return to work (RTW) of individuals with earthquake injuries.
      Providing tangible emotional and social support so injured earthquake survivors
      feel safe in their workplace may facilitate RTW. Engaging early with employers
      may assist the RTW of injured earthquake survivors.

PMID- 26213244
TI  - Work-related problems in multiple sclerosis: a literature review on its
      associates and determinants.
AB  - PURPOSE: To explore which variables are associated to or determinants of work
      related difficulties or unemployment in persons with multiple sclerosis (MS).
      METHOD: Papers published between 1993 and February 2015 were included. Quality
      was judged as poor, acceptable, good or excellent. Determinants were extracted
      from prospective and retrospective data, associated variables from cross
      sectional data; variables were grouped by similarity. Evidence was judged as
      strong if there were at least two good studies reporting the same results;
      limited if there was only one good and some acceptable studies. RESULTS: Forty
      two papers were selected, for a total of 31,192 patients (75% females). Work
      related difficulties were referred as unemployment, lower amount of worked hours
      or job cessation. Strong evidence of impact over work-related difficulties was
      found for a core set of variables, i.e., expanded disability status scale, MS
      duration, patients' age, fatigue and walking problems. Little evidence exists on
      the impact of contextual factors. DISCUSSION: Most of the variables identified as
      associated to or determinants of work-related difficulties can be treated through
      rehabilitative interventions. It is important that future research addresses not
      only unemployment issues in MS, but also the amount and severity of problems
      affecting work-related tasks relying on specific assessment instruments.
      IMPLICATIONS FOR REHABILITATION: Multiple sclerosis (MS) affects young persons of
      working age and limitation in work activities is part of MS-related disability,
      but they are not consistently addressed in MS research: EDSS, MS duration,
      patients' age, fatigue, walking problems, cognitive and neuropsychological
      impairments were the factors most commonly found as associated to or determinant
      of difficulties with work. Evidence exists that rehabilitation interventions are
      effective for fatigue, cognitive impairment, mobility and walking difficulties.
      However, research did not address the impact of rehabilitation programmes on
      vocational outcomes. Rehabilitation researchers should include MS-specific
      assessment instruments for work-related difficulties to standardised clinical
      protocols, so that the benefits of rehabilitation on persons' ability to work can
      be demonstrated directly: in this way, cost-benefit balance analyses can be added
      to the evaluation of treatment effectiveness.

PMID- 26213245
TI  - The psychotropic education and knowledge test for nurses in nursing homes:
      striving for PEAK performance.
AB  - OBJECTIVES: The psychotropic education and knowledge test for nurses in acute
      geriatric care (PEAK-AC) measures knowledge of psychotropic indications, doses
      and adverse drug reactions in older inpatients. Given the low internal
      consistency and poor discrimination of certain items, this study aims to adapt
      the PEAK-AC, validate it in the nursing home setting and identify factors related
      to nurses' knowledge of psychotropics. METHOD: This study included nurses and
      nurse assistants employed by nursing homes (n = 13) and nursing students at
      educational institutions (n = 5) in Belgium. A Delphi technique was used to
      establish content validity, the known groups technique for construct validity
      (nrespondents = 550) and the test-retest procedure for reliability (nrespondents
      = 42). Internal consistency and item analysis were determined. RESULTS: The
      psychotropic education and knowledge test for nurses in nursing homes (PEAK-NH)
      (nitems = 19) demonstrated reliability (kappa = 0.641) and internal consistency
      (Cronbach's alpha = 0.773). Significant differences between-group median scores
      were observed by function (p < 0.001), gender (p = 0.019), educational background
      (p < 0.001), work experience (p = 0.008) and continuing education (p < 0.001) for
      depression, delirium and pharmacotherapy topics. Items were acceptably difficult
      (nitems = 15) and well-functioning discriminators (nitems = 17). Median PEAK-NH
      score was 9/19 points (interquartile range 6-11 points). Respondents' own
      estimated knowledge was related to their PEAK-NH performance (p < 0.001).
      CONCLUSION: The PEAK-NH is a valid and reliable instrument to measure nurses'
      knowledge of psychotropics. These results suggest that nurses have limited
      knowledge of psychotropic use in nursing homes and are aware of their knowledge
      deficits. The PEAK-NH enables educational initiatives to be targeted and their
      impact on nurses' knowledge to be tracked.

PMID- 26213246
TI  - Proximate composition and nutritional quality of deep sea growth sea cucumbers
      (Stichopus japonicus) from different origins.
AB  - BACKGROUND: Deep sea growth sea cucumber (Stichopus japonicus) (DSG-SC) is
      considered a most nutritious and luxurious seafood in Asia. This study compared
      the proximate composition and nutritional quality of collagen, polysaccharides,
      amino acids (AAs) and fatty acids (FAs) in DSG-SCs from different origins.
      RESULTS: The contents of protein, ash, carbohydrate, fat, collagen, saturated
      fatty acids (SFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty
      acids (PUFAs), total amino acids (TAAs), essential amino acids (EAAs), fucose and
      uronic acid differed among the origins. DSG-SC of Dalian origin had lower
      contents of ash, fat, uronic acid, TAAs and EAAs but higher contents of protein,
      collagen, PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and
      fucose compared with the other origins. DSG-SCs had a higher proportion of PUFAs
      and were richer in polysaccharides than other seafood. Glutamate and glycine were
      the dominant AAs, while leucine and threonine were the most abundant EAAs.
      CONCLUSION: DSG-SCs are a good source of collagen, polysaccharides (especially
      fucose), EAAs (especially leucine and threonine) and PUFAs (especially EPA and
      DHA). Dalian seems to be a promising origin to produce high-value sea cucumber
      with high PUFA, fucose, collagen and protein contents. (c) 2015 Society of
      Chemical Industry.

PMID- 26213247
TI  - The WHO clinical case definition for suspected cases of Ebola virus disease
      arriving at Ebola holding units: reason to worry?

PMID- 26213248
TI  - Clinical features of patients isolated for suspected Ebola virus disease at
      Connaught Hospital, Freetown, Sierra Leone: a retrospective cohort study.
AB  - BACKGROUND: The size of the west African Ebola virus disease outbreak led to the
      urgent establishment of Ebola holding unit facilities for isolation and
      diagnostic testing of patients with suspected Ebola virus disease. Following the
      onset of the outbreak in Sierra Leone, patients presenting to Connaught Hospital
      in Freetown were screened for suspected Ebola virus disease on arrival and, if
      necessary, were admitted to the on-site Ebola holding unit. Since demand for beds
      in this unit greatly exceeded capacity, we aimed to improve the selection of
      patients with suspected Ebola virus disease for admission by identifying
      presenting clinical characteristics that were predictive of a confirmed
      diagnosis. METHODS: In this retrospective cohort study, we recorded the
      presenting clinical characteristics of suspected Ebola virus disease cases
      admitted to Connaught Hospital's Ebola holding unit. Patients were subsequently
      classified as confirmed Ebola virus disease cases or non-cases according to the
      result of Ebola virus reverse-transcriptase PCR (EBOV RT-PCR) testing. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and likelihood ratio of every clinical characteristic were calculated, to
      estimate the diagnostic accuracy and predictive value of each clinical
      characteristic for confirmed Ebola virus disease. RESULTS: Between May 29, 2014,
      and Dec 8, 2014, 850 patients with suspected Ebola virus disease were admitted to
      the holding unit, of whom 724 had an EBOV RT-PCR result recorded and were
      included in the analysis. In 464 (64%) of these patients, a diagnosis of Ebola
      virus disease was confirmed. Fever or history of fever (n=599, 83%), intense
      fatigue or weakness (n=495, 68%), vomiting or nausea (n=365, 50%), and diarrhoea
      (n=294, 41%) were the most common presenting symptoms in suspected cases.
      Presentation with intense fatigue, confusion, conjunctivitis, hiccups, diarrhea,
      or vomiting was associated with increased likelihood of confirmed Ebola virus
      disease. Three or more of these symptoms in combination increased the probability
      of Ebola virus disease by 3.2-fold (95% CI 2.3-4.4), but the sensitivity of this
      strategy for Ebola virus disease diagnosis was low. In a subgroup analysis, 15
      (9%) of 161 confirmed Ebola virus disease cases reported neither a history of
      fever nor a risk factor for Ebola virus disease exposure. INTERPRETATION:
      Discrimination of Ebola virus disease cases from patients without the disease is
      a major challenge in an outbreak and needs rapid diagnostic testing. Suspected
      Ebola virus disease case definitions that rely on history of fever and risk
      factors for Ebola virus disease exposure do not have sufficient sensitivity to
      identify all cases of the disease. FUNDING: None.

PMID- 26213249
TI  - The Israeli public health response to wild poliovirus importation.
AB  - In 2013, a silent wild poliovirus type 1 importation and sustained transmission
      event occurred in southern Israel. With the aim of preventing clinical
      poliomyelitis and ensuring virus re-elimination, the public health response to
      the importation event included intensification of clinical and environmental
      surveillance activities, enhancement of vaccine coverage, and supplemental
      immunisation with a bivalent oral polio vaccine against wild poliovirus types 1
      and 3. A national campaign launched in August, 2013, resulted in vaccination of
      943,587 children younger than 10 years (79% of the eligible target population).
      Expanded environmental surveillance (roughly 80% population coverage) documented
      a gradual disappearance of wild poliovirus type 1 in the country from September,
      2013, to April, 2014. No paralytic poliomyelitis case was detected. A prompt
      extensive and coordinated national public health response, implemented on the
      basis of evidence-based decision making, successfully contained this serious
      importation and sustained transmission event of wild poliovirus to Israel. On
      April 28, 2015, WHO officially declared Israel as a polio-free country.

PMID- 26213251
TI  - Association between dental caries and out-of-hospital cardiac arrests of cardiac
      origin in Japan.
AB  - BACKGROUND: Oral infection contributes to atherosclerosis and coronary heart
      disease. We hypothesized that dental caries may be associated with out-of
      hospital cardiac arrests (OHCA) of cardiac origin, but not non-cardiac origin.
      METHODS AND RESULTS: We compared the age-adjusted incidence of OHCA (785,591
      cases of OHCA: 55.4% of cardiac origin and 44.6% of non-cardiac origin) to the
      age-adjusted prevalence of dental caries between 2005 and 2011 in the 47
      prefectures of Japan. In both the total population and males over 65 years, the
      number of cases of dental caries was significantly associated with the number of
      OHCA of total and cardiac origin from 2005 to 2011, but not those of non-cardiac
      origin. In the total population, the age-adjusted prevalence of dental caries was
      not significantly associated with the age-adjusted incidence of OHCA (total OHCA:
      r correlation coefficient=0.22, p=0.14; OHCA of cardiac origin: r=0.25, p=0.09;
      OHCA of non-cardiac origin: r=-0.002, p=0.99). Among male patients over 65 years,
      the age-adjusted prevalence of dental caries was significantly associated with
      OHCA of total and cardiac origin, but not non-cardiac origin (total OHCA: r=0.47,
      p<0.001; OHCA of cardiac origin: r=0.37, p=0.01; OHCA of non-cardiac origin:
      r=0.28, p=0.054). CONCLUSIONS: While oral hygiene is important in all age groups,
      it may be particularly associated with OHCAs of cardiac origin in males over 65
      years.

PMID- 26213250
TI  - Prevalence and distribution of coronary calcium in asymptomatic Japanese subjects
      in lung cancer screening computed tomography.
AB  - BACKGROUND: Coronary artery calcium (CAC) is associated with a risk of coronary
      heart disease. The prevalence and distribution of the CAC score have been
      examined in Western countries, but few studies have been performed in Asia, and
      especially in Japan. The goal of this study was to investigate CAC scores in an
      asymptomatic Japanese population. METHODS: CAC score and risk factors were
      analyzed in 1834 asymptomatic subjects who underwent lung cancer screening
      computed tomography. RESULTS: CAC was present in 26.9% of all the subjects, 29.8%
      of the males, and 17.1% of the females. In all age groups, the CAC score was
      higher in males. In multivariate analysis, male gender [odds ratio (OR) 2.461,
      95% confidence interval (CI) 1.361-4.452, p=0.002], aging (OR 1.102, 95% CI 1.081
      1.123, p<0.001), dyslipidemia (OR 1.740, 95% CI 1.216-2.490, p=0.002), and
      fasting glucose (OR 1.008, 95% CI 1.002-1.015, p=0.012) were significantly
      associated with a CAC score >100. CONCLUSION: The results of this study provide a
      pattern of CAC distribution based on age and gender in asymptomatic Japanese
      subjects. This pattern was similar to that in Western countries, although the
      absolute CAC scores were lower. High CAC scores were associated with male gender,
      aging, dyslipidemia, and fasting glucose.

PMID- 26213252
TI  - Transepithelial transport of phenolic acids in Flos Lonicerae Japonicae in
      intestinal Caco-2 cell monolayers.
AB  - The oral bioavailabilities of phenolic acids in Flos Lonicerae Japonicae beverage
      were low. The observation from an in vitro Caco-2 cell model showed that the
      absorptions of phenolic acids were mainly permeated via paracellular diffusion,
      and influenced by P-glycoprotein (P-gp), multidrug resistance-associated protein
      2 (MRP2) and breast cancer resistance protein (BCRP). Besides, the Papp (AP->BL)
      values in Flos Lonicerae Japonicae were significantly higher than those of
      monomers, which was attributed to the decrease of efflux ratios (<1.0) influenced
      by flavones (luteoloside and luteolin) on the P-gp, but they were still poorly
      absorbed. The results indicated that the absorptions in Flos Lonicerae Japonicae
      as well as those of monomers were mainly restricted by the tight junctions (TJs).
      Food supplements (honey and propolis) or edible excipient (chitooligosaccharide)
      as TJ enhancers will be investigated to improve the functions of Flos Lonicerae
      Japonicae healthy beverages. 

PMID- 26213253
TI  - 4D flow MRI can detect subtle right ventricular dysfunction in primary left
      ventricular disease.
AB  - PURPOSE: To investigate whether 4D flow magnetic resonance imaging (MRI) can
      detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV)
      disease. MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were
      acquired in 22 patients with mild ischemic heart disease who were stratified into
      two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher
      LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end
      diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and
      traced forwards and backwards in time to ES. The blood volume was separated into
      flow components. The Direct Flow (DF) component was defined as RV inflow passing
      directly to outflow. The kinetic energy (KE) of the DF component was calculated.
      Echocardiographic conventional RV indices were also assessed. RESULTS: The higher
      LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 +/- 32 ml/m(2)
      ; 48 +/- 13%) compared to the healthy (67 +/- 12, P = 0.002; 64 +/- 7, P < 0.001)
      and lower-LVEDI groups (62 +/- 10; 68 +/- 7, both P < 0.001). The RV 4D flow
      specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in
      the higher-LVEDVI group (38 +/- 5%; 52 +/- 6%) compared to the healthy (44 +/- 6;
      65 +/- 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 +/- 6; 64 +/- 7, P
      = 0.011 and P < 0.001). There was no difference in any of the conventional MRI
      and echocardiographic RV indices between the three groups. CONCLUSION: We found
      that in primary LV disease mild impairment of RV function can be detected by 4D
      flow-specific measures, but not by the conventional MRI and echocardiographic
      indices.

PMID- 26213254
TI  - The association between involuntary memory and emotional adjustment after
      childbirth.
AB  - OBJECTIVES: A woman's memory of her experience of giving birth can strongly
      influence her mental health, and the development of her relationship with her
      infant, in a positive or negative direction. Highly distressing, involuntary
      memories of the birth may indicate symptoms of post-traumatic stress (PTS), which
      is increasingly recognized as a possible outcome of childbirth. Involuntary
      memories are not, however, exclusive to trauma and can also be experienced after
      positive events. This study sought to investigate involuntary memories for
      childbirth, as this is an event that is known to be potentially experienced both
      as highly positive and negative, and associated with a range of emotional
      outcomes, including greater well-being and symptoms of PTS. METHODS: A total of
      122 women completed a measure of their emotional experience of giving birth
      within 3 days of the event, and 65 of these women responded to a postal follow-up
      at 6 weeks, with measures of involuntary memory experience, PTS symptoms and well
      being. RESULTS: Experiencing pleasant involuntary memories was more common than
      experiencing unpleasant involuntary memories of the birth. The frequency of these
      memories and how they were experienced as either distressing or enjoyable was
      associated with post-partum emotional adjustment, demonstrated by the development
      of PTS symptoms or greater well-being. CONCLUSIONS: These results are important
      because to date, little research has examined the development of positive
      involuntary memories and their association with positive emotional adjustment.
      Statement of contribution What is already known on this subject? Positive and
      negative emotional experiences can coexist in childbirth. Involuntary memories
      after negative events can be associated with post-traumatic stress. Involuntary
      memories can also occur after strongly positive events. What does this study add?
      Women can experience both positive and negative involuntary memories after
      childbirth. Involuntary negative memories mediate the link between birth
      experience and post-traumatic stress. Positive involuntary memories are
      associated with greater well-being in the post-partum. Transformation of
      negatively experienced events into positively experienced involuntary memories
      may facilitate adjustment after childbirth.

PMID- 26213255
TI  - Characteristics of depression in community-dwelling elderly people as indicated
      by the tree-drawing test.
AB  - BACKGROUND: The tree-drawing test (TDT) is a typical projective method, but
      previous studies have paid little attention to it for elderly people. We
      investigated the characteristics of depression in community-dwelling elderly
      people as indicated by the TDT. METHODS: This study was a complete enumeration
      survey of elderly people conducted through home visits. The contents of the
      survey included gender, age, presence or absence of housemates, frequency of
      going out, the 15-item Geriatric Depression Scale, and TDT. The subjects were
      divided into three groups (normal, depressed tendency, and depressed) according
      to the total 15-item Geriatric Depression Scale score. RESULTS: In TDT, no
      significant difference was observed in drooping crown, shadow of the whole tree,
      or shadow near the base, which have been regarded as indices of depression in
      younger people. However, the values concerning the size of the tree, such as the
      height and width of the whole tree, height and width of the crown, and number of
      occupied areas (of the paper), were significantly lower in the depressed group
      than in the other groups. In addition, the width of the trunk was significantly
      smaller in the depressed group than in the normal group. Subjects were classified
      as being in a 'depressed state' if they used 40 or fewer areas for drawing (i.e.
      occupied areas) and a 'non-depressed state' if they used 41 or more areas. This
      enabled depression to be detected (sensitivity: 71.4%; specificity: 79.9%).
      CONCLUSIONS: The size of the tree in TDT is suggested to reflect characteristics
      of depression in elderly people, such as introversion, reserve, antisocial
      attitude, a feeling of inferiority, weakness of ego, and lack of vigour.
      Furthermore, the numbers of occupied areas were found to be relatively useful in
      detecting depression in elderly people.

PMID- 26213256
TI  - Patients' experiences of adapting to multiple sclerosis: a qualitative study.
AB  - Unpleasant, unpredictable symptoms, difficult treatment regimes, and uncertainty
      about the future of Multiple Sclerosis require the patients to adapt to new life
      changes and restrictions. This study aimed to explore patients' experiences of
      adapting to Multiple Sclerosis. A qualitative content analysis method was used to
      conduct this study. The study participants were 25 patients with Multiple
      Sclerosis, chosen through purposeful sampling. Data were analyzed by using
      content analysis. The analysis resulted in the emergence of seven themes and
      eighteen subthemes. The main themes were: religiosity, information seeking,
      seeking support, hope rearing, emotional reactions, concealing the disease,
      fighting the disease and disability. These themes can represent the perceived
      characteristics and difficulties of adaptation to Multiple Sclerosis by patients.
      These findings can help nurses and families to aid patients in increasing their
      abilities to adapt to the disease and enhance their quality of life. 

PMID- 26213257
TI  - Determination of nursing students' expectations for faculty members and the
      perceived stressors during their education.
AB  - BACKGROUND: In nursing education, there are several different factors which can
      affect the efficacy and quality of the education besides the interaction between
      the students and the educator. The necessity of giving theoretical and clinical
      education together may lead to various difficulties. PURPOSE: We aimed to
      determine the features of faculties that are most sought after by nursing
      students and to identify the conditions that lead to stress in the education
      process. METHODS: This was a descriptive study. The data were gathered using a
      collection form that was prepared by the researchers and included questions about
      the students' expectations of the faculty and the conditions that caused stress
      in the students. RESULTS: The students' leading expectations of the faculty were
      'doing fair evaluation of being prepared for the lesson and knowing the subject
      well', 'knowing and using the proper education methods, techniques and strategies
      while teaching', 'the unprejudiced behaviour of the faculty towards the student
      and communicating well', 'being objective towards the students and making an
      objective assessment' and 'being good at both practice and theoretical
      knowledge'. 'Intensive theoretical lessons', 'crowded classes', 'monotonous and
      boring lessons', 'the negative behaviours of the nurses/doctors or the patients',
      'fear of failure or making mistakes during the clinical practice' and 'seeing a
      dying patient' were the most stressful conditions for the students. CONCLUSION:
      The ways in which these factors affect the education process must be evaluated in
      nursing education based on a combination of theoretical and practical education
      and learning experiences. The results obtained from this study could be a guide
      for nursing schools and faculties.

PMID- 26213258
TI  - Workplace incivility: a concept analysis.
AB  - This study aimed to describe the meaning of the concept 'workplace incivility'
      and promote consistency in its application in nursing research and practice. The
      methodology introduced by Walker and Avant was used to analyze this concept. A
      total number of 50 studies that had essentially addressed the concept of
      incivility in employees' work environment was selected. Ambiguous intent,
      violation of mutual respect, low intensity and lack of physical assault were
      identified as the defining attributes of workplace incivility. The necessary
      antecedent of workplace incivility consisted of the presence of two or more
      people, with one or more as the source of the incivility, and another or others
      as its target in the workplace. Moreover, certain individual and organisational
      factors were the potential antecedents of workplace incivility. Possible negative
      outcomes for victims, witnesses, organisations, society and perpetrators of such
      behaviours, such as increased cost for the organisation, reduced citizenship
      performance, psychological distress and anxiety were identified as outcomes of
      workplace incivility. Results of the current concept analysis can guide nurse
      managers to design interventions so that the occurrence of workplace incivility
      can be reduced. Further studies can focus on testing the psychometric properties
      of the existing workplace incivility scales, especially uncivil behaviours
      experienced by nurses across different societies or cultures. 

PMID- 26213259
TI  - Fluorescence sensing of ADP over ATP and PPi in 100% aqueous solution.
AB  - An anthracene-bridged dinuclear zinc(ii)-dipicolylamine complex was found to show
      high selectivity for ADP with a significant fluorescence enhancement over ATP,
      PPi and other common analytes in 100% aqueous solution. This complex can be used
      for fluorescence detection of ADP in living cells and for monitoring the activity
      of kinases. 

PMID- 26213261
TI  - Understanding the Outstanding Power Conversion Efficiency of Perovskite-Based
      Solar Cells.

PMID- 26213260
TI  - In Vivo Integrity and Biological Fate of Chelator-Free Zirconium-89-Labeled
      Mesoporous Silica Nanoparticles.
AB  - Traditional chelator-based radio-labeled nanoparticles and positron emission
      tomography (PET) imaging are playing vital roles in the field of nano-oncology.
      However, their long-term in vivo integrity and potential mismatch of the
      biodistribution patterns between nanoparticles and radio-isotopes are two major
      concerns for this approach. Here, we present a chelator-free zirconium-89
      ((89)Zr, t1/2 = 78.4 h) labeling of mesoporous silica nanoparticle (MSN) with
      significantly enhanced in vivo long-term (>20 days) stability. Successful radio
      labeling and in vivo stability are demonstrated to be highly dependent on both
      the concentration and location of deprotonated silanol groups (-Si-O(-)) from two
      types of silica nanoparticles investigated. This work reports (89)Zr-labeled MSN
      with a detailed labeling mechanism investigation and long-term stability study.
      With its attractive radio-stability and the simplicity of chelator-free radio
      labeling, (89)Zr-MSN offers a novel, simple, and accurate way for studying the in
      vivo long-term fate and PET image-guided drug delivery of MSN in the near future.

PMID- 26213262
TI  - Breast fibromatosis associated with breast implants.
AB  - Fibromatosis refers to an extra-abdominal desmoid tumor or aggressive
      fibromatosis. Breast fibromatosis can develop in association with the capsule
      around a breast implant, although reports of cases of fibromatosis associated
      with breast implants are rare. As the demand for breast augmentation has
      increased, it is important to understand the diseases associated with breast
      implants. In the present report, we describe a case of breast fibromatosis that
      developed adjacent to a breast implant and demonstrated a relatively well-defined
      border even though it invaded the surrounding structures. We also explore the
      specific imaging features for diagnosing breast fibromatosis in association with
      implants by reviewing previous literature. 

PMID- 26213263
TI  - Human sports drug testing by mass spectrometry.
AB  - Since the installation of anti-doping rules and regulations and their
      international enforcement in the mid-1960s, mass spectrometry has been an
      integral part of doping control procedures. Although its utility was limited in
      the first decade, instrumental improvements and method optimizations have made
      mass spectrometry, in all its facets, an indispensable tool in modern sports drug
      testing. In this review, milestones in doping control analysis accomplished in
      Germany and reaching from the early developments to the current use of hyphenated
      mass spectrometric techniques concerning low- and high molecular mass analytes
      are presented. The considered drug classes include anabolic agents, peptidic
      drugs, nucleotide-derived therapeutics, approved and non-approved organic as well
      as inorganic analytes, and particular focus is put on drug class- and instrument
      driven strategies. (c) 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:16-46, 2017.

PMID- 26213264
TI  - Bacteriophage membrane protein P9 as a fusion partner for the efficient
      expression of membrane proteins in Escherichia coli.
AB  - Despite their important roles and economic values, studies of membrane proteins
      have been hampered by the difficulties associated with obtaining sufficient
      amounts of protein. Here, we report a novel membrane protein expression system
      that uses the major envelope protein (P9) of phage phi6 as an N-terminal fusion
      partner. Phage membrane protein P9 facilitated the synthesis of target proteins
      and their integration into the Escherichia coli cell membrane. This system was
      used to produce various multi-pass transmembrane proteins, including G-protein
      coupled receptors, transporters, and ion channels of human origin. Green
      fluorescent protein fusion was used to confirm the correct folding of the
      expressed proteins. Of the 14 membrane proteins tested, eight were highly
      expressed, three were moderately expressed, and three were barely expressed in E.
      coli. Seven of the eight highly expressed proteins could be purified after
      extraction with the mild detergent lauryldimethylamine-oxide. Although a few
      proteins have previously been developed as fusion partners to augment membrane
      protein production, we believe that the major envelope protein P9 described here
      is better suited to the efficient expression of eukaryotic transmembrane proteins
      in E. coli. 

PMID- 26213265
TI  - Accuracy of 3 different impression techniques for internal connection angulated
      implants.
AB  - STATEMENT OF PROBLEM: Making implant impressions with different angulations
      requires a more precise and time-consuming impression technique. PURPOSE: The
      purpose of this in vitro study was to compare the accuracy of nonsplinted,
      splinted, and snap-fit impression techniques of internal connection implants with
      different angulations. MATERIAL AND METHODS: An experimental device was used to
      allow a clinical simulation of impression making by means of open and closed tray
      techniques. Three different impression techniques (nonsplinted, acrylic-resin
      splinted, and indirect snap-fit) for 6 internal-connected implants at different
      angulations (0, 15, 25 degrees) were examined using polyether. Impression
      accuracy was evaluated by measuring the differences in 3-dimensional (3D)
      position deviations between the implant body/impression coping before the
      impression procedure and the coping/laboratory analog positioned within the
      impression, using a coordinate measuring machine. Data were analyzed by 2-way
      ANOVA. Means were compared with the least significant difference criterion at
      P<.05. RESULTS: Results showed that at 25 degrees of implant angulation, the
      highest accuracy was obtained with the splinted technique (mean +/-SE: 0.39 +/
      0.05 mm) and the lowest with the snap-fit technique (0.85 +/-0.09 mm); at 15
      degrees of angulation, there were no significant differences among splinted (0.22
      +/-0.04 mm) and nonsplinted technique (0.15 +/-0.02 mm) and the lowest accuracy
      obtained with the snap-fit technique (0.95 +/-0.15 mm); and no significant
      differences were found between nonsplinted and splinted technique at 0 degrees of
      implant placement. CONCLUSIONS: Splinted impression technique exhibited a higher
      accuracy than the other techniques studied when increased implant angulations at
      25 degrees were involved.

PMID- 26213266
TI  - Effect of heating palladium-silver alloys on ceramic bond strength.
AB  - STATEMENT OF PROBLEM: The effects of different heat treatments on the internal
      oxidation and metal-ceramic bond in Pd-Ag alloys with different trace elements
      require further documentation. PURPOSE: The purpose of this in vitro study was to
      determine whether heat treatment affects the metal-ceramic bond strength of 2 Pd
      Ag alloys containing different trace elements. MATERIAL AND METHODS: Thirteen
      cast specimens (25*3*0.5 mm) from each of 2 Pd-Ag alloy groups (W-1 and Argelite
      61+3) were allocated to heat treatments before porcelain application: heating
      under reduced atmospheric pressure of 0.0014 MPa and 0.0026 MPa and heating under
      normal atmospheric pressure. Bond strengths were evaluated using a 3-point
      bending test according to ISO9693. Results were analyzed using 2-way ANOVA and
      Tukey HSD test (alpha=.05). Visual observation was used to determine the failure
      types of the fractured specimens. Scanning electron microscopy and energy
      dispersive spectroscopy were used to study morphologies, elemental compositions,
      and distributions in the specimens. RESULTS: The W-1 group had a mean bond
      strength significantly higher than that of Argelite 61+3 (P<.001). Heating under
      reduced atmospheric pressures of 0.0014 MPa and 0.0026 MPa resulted in similar
      bond strengths (P=.331), and both pressures had significantly higher bond
      strengths than that of heating under normal atmospheric pressure (P=.002,
      P<.001). Heating under different air pressures resulted in Pd-Ag alloys that
      contained either Sn or In and Ga, with various degrees of internal oxidation and
      different quantities of metallic nodules. CONCLUSIONS: Heating under reduced
      atmospheric pressure effectively improved the bond strength of the ceramic-to-Pd
      Ag alloys.

PMID- 26213267
TI  - Internal and marginal fit of cobalt-chromium fixed dental prostheses fabricated
      with 3 different techniques.
AB  - STATEMENT OF PROBLEM: Conventionally, the fabrication method for Co-Cr
      restorations has been casting by the lost-wax method. Milling and selective laser
      melting (SLM) are more cost effective and thereby increasingly used. The
      precision of the different methods regarding internal and marginal fit, however,
      is not fully known. PURPOSE: The purpose of this in vitro study was to examine
      and evaluate whether the 3 fabrication methods of conventional casting, milling,
      and SLM differ in internal and marginal fit for Co-Cr fixed dental prostheses
      (FDPs). MATERIAL AND METHODS: Thirty Co-Cr metal frameworks for 3-unit FDPs were
      made with 3 fabrication methods for a model with 2 abutment preparations.
      Internal fit was measured with the replica method. A white silicone indicator
      material simulated the cement space. This was measured by light microscopy at *20
      magnification and a digital measurement program. Marginal fit was evaluated with
      the direct-sight technique at *4.6 magnification and given a score from 1 to 5.
      One-way ANOVA and Tukey honest significance tests were used to evaluate
      differences among groups with regard to internal fit. The Kruskal-Wallis and Mann
      Whitney U tests were used to calculate differences among groups with regard to
      marginal gap. The Pearson r test was used for correlations calculations
      (alpha=.05). RESULTS: Statistically significant differences were found in both
      internal and marginal fit among the test groups (P<.003). The milled group had
      the best overall fit, followed by the cast and SLM groups. CONCLUSIONS: SLM
      restorations had the poorest internal and marginal fit, whereas the milling
      method had the best results. The SLM technique did not achieve clinically
      acceptable values for internal fit.

PMID- 26213268
TI  - Vertical preparation for fixed prosthesis rehabilitation in the anterior sector.
AB  - This clinical report describes a biologically oriented preparation technique
      (BOPT) for teeth and an implant for the esthetic rehabilitation of the maxillary
      anterior sector. The technique was designed to create an anatomic crown with a
      prosthetic emergence profile that simulated the shape of the natural tooth. 

PMID- 26213269
TI  - Ancient marine hunter-gatherers from Patagonia and Tierra Del Fuego: Diversity
      and differentiation using uniparentally inherited genetic markers.
AB  - OBJECTIVES: The human population history from Patagonia and Tierra del Fuego has
      been of great interest in the context of the American peopling. Different sources
      of evidence have contributed to the characterization of the local populations,
      but some main questions about their history remain unsolved. Among the native
      populations, two marine hunter-gatherers groups inhabited the Patagonian channels
      below the 478S: Kaweskar and Yamana. Regardless of their geographical proximity
      and cultural resemblance, their languages were mutually unintelligible. In this
      study we aim to evaluate the genetic diversity of uniparental genetic markers in
      both groups and to test if there is a high genetic differentiation between them,
      mirroring their linguistic differences. MATERIAL AND METHODS: Ancient DNA was
      extracted from 37 samples from both populations. We compared their genetic
      variability of their mitochondrial lineages and Y-STR as well as with other
      modern native populations from the area and further north. RESULTS AND
      DISCUSSION: We observed an important differentiation in their maternal lineages:
      while Kaweskar shows a high frequency of D (80%), Yamana shows a high frequency
      of C (90%). The analysis of paternal lineages reveals the presence of only
      Q1a2a1a1 and little variation was found between individuals. Both groups show
      very low levels of genetic diversity compared with modern populations. We also
      notice shared and unique mitochondrial DNA variants between modern and ancient
      samples of Kaweskar and Yamana.

PMID- 26213270
TI  - Decamethylcyclopentasiloxane (D5) environmental sources, fate, transport, and
      routes of exposure.
AB  - The environmental sources, fate, transport, and routes of exposure of
      decamethylcyclopentasiloxane (D5; CAS no. 541-02-6) are reviewed in the present
      study, with the objective of contributing to effective risk evaluation and
      assessment of this and related substances. The present review, which is part of a
      series of studies discussing aspects of an effective risk evaluation and
      assessment, was prompted in part by the findings of a Board of Review undertaken
      to comment on a decision by Environment Canada made in 2008 to subject D5 to
      regulation as a toxic substance. The present review focuses on the early stages
      of the assessment process and how information on D5's physical-chemical
      properties, uses, and fate in the environment can be integrated to give a
      quantitative description of fate and exposure that is consistent with available
      monitoring data. Emphasis is placed on long-range atmospheric transport and fate
      in water bodies receiving effluents from wastewater treatment plants (along with
      associated sediments) and soils receiving biosolids. The resulting exposure
      estimates form the basis for assessments of the resulting risk presented in other
      studies in this series. Recommendations are made for developing an improved
      process by which D5 and related substances can be evaluated effectively for risk
      to humans and the environment.

PMID- 26213271
TI  - Detection of central fixation using short-time autoregressive spectral estimation
      during retinal birefringence scanning.
AB  - The manuscript reports on the implementation of autoregressive spectral
      estimation aimed at improving the accuracy of detecting short-lasting events in
      signals acquired by a retinal birefringence scanning device that was reported
      earlier. A signal consisting of two frequency components is generated, where each
      frequency is a multiple of the scanning frequency. One frequency is produced
      during central fixation, while another one prevails during off-central fixation.
      These components may be of a very short duration, presenting a challenge for the
      FFT to identify them with sufficient time- and frequency resolution.
      Autoregressive spectral estimation using the Burg algorithm provided a
      satisfactory solution, capable of reliably differentiating between the two
      frequency components (96 and 192 Hz) on signal segments of duration as short as 5
      ms. The device and the signal analysis methods were developed originally with the
      purpose of checking for eye alignment and strabismus - a major risk factor for
      amblyopia. The method enables the technology to work with less-cooperative
      patients, such as young children. Other medical and non-medical applications are
      possible.

PMID- 26213272
TI  - Multicenter retrospective investigation into migration of fenestrated aortic
      stent grafts.
AB  - OBJECTIVE: Fenestrated stent grafts are subject to the same hemodynamic forces
      that have resulted in migration of standard infrarenal stent grafts. Outcome data
      for fenestrated endovascular aneurysm repair consist of short-term and midterm
      efficacy studies where migration was generally poorly investigated. This study
      investigated the migration of fenestrated stent grafts in patients treated by
      fenestrated endovascular aneurysm repair in the United Kingdom. METHODS: A total
      of 154 patients were retrospectively enrolled from nine sites across the United
      Kingdom. Patients had been treated with a Zenith fenestrated endograft (Cook
      Medical, Bloomington, Ind) between 2003 and 2010. Patients were required to have
      a baseline (first) postoperative computed tomography (CT) scan and at least one
      additional CT scan available. Measurements from the proximal stent graft to the
      superior mesenteric artery and from the distal stent graft to the iliac
      bifurcation were performed on the first postoperative CT scan. These measurements
      were repeated on all subsequent CT scans, and differences between the baseline
      and subsequent CT scans for the same anatomical location were suggestive of
      device migration. Migration was defined as cranial (-) or caudal (+) movement of
      the stent graft of >=4 mm. RESULTS: Proximal migration (median, +6.0 mm; range,
      +4.1 to +10.0 mm) was evident in 33 patients (21%). The probability of being free
      from proximal migration at 12, 24, and 36 months was estimated as 82% (95%
      confidence interval [CI], 75%-89%), 77% (95% CI, 70%-85%), and 77% (95% CI, 70%
      85%), respectively. Of 259 limbs assessed, 34 (13%) showed evidence of cranial
      migration (median, -6.1 mm; range, -21.3 to -4.1 mm). The observed probability of
      being free from any iliac limb migration at 12, 24, and 36 months was 85% (95%
      CI, 79%-92%), 82% (95% CI, 75%-90%), and 65% (95% CI, 52%-80%), respectively.
      CONCLUSIONS: Proximal migration occurs in approximately one-third of patients by
      4 years, all migration was caudal in direction, with 60% <6.0 mm in length.
      Clinical sequelae were infrequent, with no statistically significant differences
      in the number of complications or reinterventions in patients with and without
      proximal migration.

PMID- 26213273
TI  - Renal artery aneurysms.
AB  - Renal artery aneurysms are rare in the general population, although the true
      incidence and natural history remain elusive. Controversy over criteria for
      repair persists across decades. Indications for repair presently include aneurysm
      size >2 cm, female gender within childbearing age, symptoms like pain and
      hematuria, medically refractory hypertension including that associated with
      functionally important renal artery stenosis, thromboembolism, dissection, and
      rupture. Conventional surgical reconstruction options are variable and continue
      to offer technically sound and durable results. Endovascular therapies with novel
      devices also offer technical success with few major adverse events, and are
      increasingly employed as indications for intervention broaden. This review
      summarizes the accumulated evidence on true renal artery aneurysms with a
      particular focus on contemporary treatment criteria, natural history, options for
      repair and outcomes following such.

PMID- 26213274
TI  - Aortic neck enlargement after endovascular aneurysm repair using balloon
      expandable versus self-expanding endografts.
AB  - OBJECTIVE: This study evaluated changes in aortic neck diameter after
      endovascular aneurysm repair (EVAR) using a balloon-expandable stent (BES)
      endograft compared with a commercially available self-expanding stent (SES)
      endograft. We hypothesized that forces applied to the aortic neck by SES
      endografts may induce aortic neck enlargement over time and that such enlargement
      may not occur in aneurysm patients treated with a device that does not use a
      proximal SES. METHODS: This was a retrospective quantitative computed tomography
      (CT) image analysis of patients treated with the Nellix (Endologix, Irvine,
      Calif) BES (n = 49) or the Endurant II (Medtronic, Minneapolis, Minn) SES (n =
      56) endograft from 2008 to 2010. Patients with preimplant, postimplant, and at
      least 1-year serial CT scans underwent quantitative morphometric assessment by
      two independent vascular radiologists blinded to the outcome results. Changes in
      the infrarenal neck over time were compared with the suprarenal aorta for each
      patient. RESULTS: Follow-up extended to 4.8 years for the BES and to 4.6 years
      for the SES, with no significant difference in median follow-up time (34 months
      for BESs and 24 months for SESs; P = .06). There were no differences in
      preimplant neck diameter (25.2 +/- 0.9 mm vs 25.7 +/- 1.1 mm; P = .54) or length
      (27.7 +/- 3.7 mm vs 23.6 +/- 3.7 mm; P = .12) between BESs and SESs at baseline.
      After implantation, neck diameter increased by 1.1 +/- 0.5 mm in BES patients and
      2.6 +/- 0.5 mm in SES patients (P = .07) compared with the preoperative diameter.
      At 3 years, neck diameter increased by 0.5 +/- 0.9 mm in BES patients and by 3.8
      +/- 1.0 mm in SES patients (P = .0002) compared with the first postoperative CT
      scan. The annual postimplant rate of increase in the infrarenal neck diameter was
      fivefold greater in SES patients (1.1 +/- 0.1 mm/y) than in BES patients (0.22 +/
      0.04 mm/y; P < .0001). There were no significant differences in the diameter of
      the suprarenal aorta at baseline or at 3 years and no differences in the annual
      rate of change in suprarenal aortic diameter between BES and SES endografts.
      CONCLUSIONS: EVAR using SES endografts resulted in progressive infrarenal aortic
      neck enlargement, whereas EVAR using BES endografts resulted in no neck
      enlargement over time. These data suggest that infrarenal neck enlargement after
      EVAR with SES endografts is likely related to the force exerted by SES elements
      rather than disease progression in the infrarenal neck.

PMID- 26213275
TI  - A model to demonstrate that endotension is a nonvisualized type I endoleak.
AB  - OBJECTIVE: Unexplained aneurysm growth despite multimodality imaging after
      endovascular aneurysm repair is often attributed to endotension. We tested a
      hypothesis that endotension may be from a type Ia endoleak pressurizing the
      aneurysm sac, without net forward flow, not visualized on standard angiographic
      imaging. METHODS: A patient-specific aortic aneurysm phantom was constructed of
      polyvinyl alcohol using three-dimensional molding techniques. A bifurcated stent
      graft was implanted, and the phantom was connected to a hemodynamic simulator for
      testing. Type Ia endoleaks were created using 7F catheters. Three scenarios were
      studied: complete exclusion (no endoleak), inflow with no sac outflow, and inflow
      with sac outflow. Imaging with digital subtraction angiography was performed at
      48 kVp at 5 frames/s, followed by delayed imaging at 1 frame/min for 30 minutes.
      RESULTS: With no endoleak, the systemic pressure averaged 113 mm Hg and aneurysm
      sac pressure averaged 101 mm Hg. With an endoleak present without outflow, the
      systemic pressure averaged 116 mm Hg, the aneurysm sac pressure averaged 120 mm
      Hg, and endoleak flow was bidirectional with no net forward flow. With endoleak
      present with aneurysm sac outflow, the systemic pressure averaged 119 mm Hg,
      aneurysm sac pressure averaged 105.5 mm Hg, and net endoleak flow into the
      aneurysm sac was 21 mL/min across the endoleak channel. With digital subtraction
      imaging, the endoleak with no outflow was noted after >9 minutes of delayed
      imaging. CONCLUSIONS: In our model, the creation of a type Ia endoleak in the
      absence of sac outflow resulted in a mean pressure higher than the systemic mean
      pressure with zero net flow into the aneurysm sac. Consequently, the endoleak
      could only be visualized with markedly delayed imaging and not with standard
      contrast digital subtraction angiography like that used in clinical practice. Our
      findings suggest that endotension may in fact be the result of undetected
      endoleaks secondary to the limitations of present iodinated contrast imaging
      modalities.

PMID- 26213280
TI  - Atmospheric Degradation of CH2?C(CH3)C(O)OCH3 Initiated by OH Radicals:
      Mechanistic Study and Quantification of CH3C(O)C(O)OCH3 in NOx Free Air.
AB  - The product distribution of the gas-phase reaction of OH radicals with methyl
      methacrylate (CH2?C(CH3)C(O)OCH3, MMA) in the absence of NOx was studied at 298 K
      and atmospheric pressure of air. The experiments were performed in a Teflon
      chamber using solid-phase microextraction (SPME) with GC-MS and GC-FID for
      product identification and quantification, respectively. In the absence of NOx,
      methyl pyruvate (CH3C(O)C(O)OCH3) was identified with a yield of 76 +/- 13% in
      accordance with the decomposition of the 1,2-hydroxyalkoxy radicals formed. In
      addition, a detailed quantum chemical study of the degradation of MMA was
      performed by density functional theory (DFT) methods using the MPWB1K functional.
      This calculation suggests that formation of methyl pyruvate, from C1-C2 scission
      of 1,2-hydroxyalkoxy radical, is kinetically and thermodynamically the most
      favorable reaction path taking into account the electronic properties of reaction
      intermediates and transition states. The difference observed on the degradation
      mechanism of MMA in the presence and absence of NOx was explained in terms of the
      associated thermochemistry. Furthermore, this study propose that reaction between
      peroxy radical (RO2(*)) and hydroxyl radical (OH) became relevant at NOx-free
      environments. This statement is in agreement with recent studies concerning small
      peroxy radicals such as CH3OO(*). 

PMID- 26213281
TI  - Orbital Reconstruction in a Self-assembled Oxygen Vacancy Nanostructure.
AB  - We demonstrate the microscopic role of oxygen vacancies spatially confined within
      nanometer inter-spacing (about 1 nm) in BiFeO3, using resonant soft X-ray
      scattering techniques and soft X-ray spectroscopy measurements. Such vacancy
      confinements and total number of vacancy are controlled by substitution of Ca(2+)
      for Bi(3+) cation. We found that by increasing the substitution, the in-plane
      orbital bands of Fe(3+) cations are reconstructed without any redox reaction. It
      leads to a reduction of the hopping between Fe atoms, forming a localized valence
      band, in particular Fe 3d-electronic structure, around the Fermi level. This band
      localization causes to decrease the conductivity of the doped BiFeO3 system. 

PMID- 26213282
TI  - Editorial Comment to Advances in sentinel node dissection in prostate cancer from
      a technical perspective.

PMID- 26213283
TI  - Doubling Throughput of a Real-Time PCR.
AB  - The invention of polymerase chain reaction (PCR) in 1983 revolutionized many
      areas of science, due to its ability to multiply a number of copies of DNA
      sequences (known as amplicons). Here we report on a method to double the
      throughput of quantitative PCR which could be especially useful for PCR-based
      mass screening. We concurrently amplified two target genes using only single
      fluorescent dye. A FAM probe labelled olionucleotide was attached to a quencher
      for one amplicon while the second one was without a probe. The PCR was performed
      in the presence of the intercalating dye SYBR Green I. We collected the
      fluorescence amplitude at two points per PCR cycle, at the denaturation and
      extension steps. The signal at denaturation is related only to the amplicon with
      the FAM probe while the amplitude at the extension contained information from
      both amplicons. We thus detected two genes within the same well using a single
      fluorescent channel. Any commercial real-time PCR systems can use this method
      doubling the number of detected genes. The method can be used for absolute
      quantification of DNA using a known concentration of housekeeping gene at one
      fluorescent channel. 

PMID- 26213284
TI  - Crossing the generational divide.

PMID- 26213285
TI  - White-Light Emission from an Integrated Upconversion Nanostructure: Toward
      Multicolor Displays Modulated by Laser Power.
AB  - The white backlight in displays is generated by optimizing the proportions of
      individual emitters with different wavelengths by variations in materials
      composition, phase, and structure. Color pixels usually result from the
      separation of white light or the excitation with multiwavelength or multipulse
      sources. However, it is a challenge to develop a material that comprises a single
      structure and emits over the full visible spectrum, but where the emission
      wavelengths can be controlled by a simple excitation source. Herein, we report an
      upconversion nanostructure that incorporates several lanthanide ions in the same
      core@shell@shell structure. The combination of multiple narrow spectral bands
      results in the emission of white light. The emission colors can be tuned by
      changing the excitation power density, which manipulates the photon transfer
      pathways. Applications such as flat-panel displays and imaging have been
      demonstrated. 

PMID- 26213286
TI  - Atypical and malignant meningiomas: Considerations for treatment and efficacy of
      radiotherapy.
AB  - The purpose of this study was to add to the current body of literature which is
      aimed at establishing the role of postoperative adjuvant radiotherapy (RT) in the
      treatment of atypical and malignant meningiomas. Meningiomas are the most
      frequently reported primary intracranial tumours, accounting for more than 35%.
      The majority of meningiomas are benign, with atypical and malignant tumours
      accounting for only 6-18%. Utilising a prospective multi-institutional database,
      we retrospectively reviewed 67 patients with documented World Health Organisation
      (WHO) Grade II/III meningiomas, diagnosed between 1989 and 2012 and resected at
      two major Australian hospitals. Nine patients were excluded and the remaining 58
      were analysed. The patient demographics, tumour characteristics, surgical details
      and adjuvant therapy were retrieved. Kaplan-Meier curves were used to compare the
      survival of patients treated with RT versus surgery alone. The 3 year progression
      free survival (PFS) and overall survival (OS) were 44 and 76% for the entire
      cohort, respectively. Of the patients who had gross total resections, 42% had 3
      years PFS and 77% had 3 years OS, which was not significantly different from
      those with subtotal resection. The overall median survival was 11.0 years, 12.2
      for atypical and 1.6 for malignant meningiomas. The patients with malignant
      meningiomas were 14 times as likely to receive RT as the patients with atypical
      meningiomas. The patients who received RT had a 3 year PFS of 63% compared to 40%
      in those who did not receive radiation. The 3 year OS was 31% higher for females
      than males. Histopathological progression was noted in 17% of our cohort. This
      study reinforces a number of important factors that should be considered when
      treating patients presenting with WHO Grade II and III meningiomas, including
      sex, potential for grade progression, and the lack of evidence for adjuvant RT
      and the timing thereof.

PMID- 26213287
TI  - Surgical treatment of pituitary apoplexy in association with hemispheric
      infarction.
AB  - We report a patient with pituitary apoplexy in whom cerebral infarction
      developed, possibly secondary to vasospasm. Pituitary apoplexy is a clinical
      syndrome caused by acute hemorrhage or infarction of the pituitary gland. Our
      patient's clinical symptoms and radiographic findings greatly improved after
      surgical resection of the apoplectic pituitary gland. An extensive literature
      review was performed, including all previously reported cases of pituitary
      apoplexy leading to cerebral infarction. The clinical features,
      pathophysiological mechanisms, management and outcome of cerebral infarction
      following pituitary apoplexy are discussed. We show that cerebral infarction
      following pituitary apoplexy is associated with much poor prognosis. Early
      surgical decompression of the tumor and hemisphere should be performed in
      patients with severe or progressive neurological deficits, however, those with
      less severe presentations may be treated conservatively or with delayed elective
      surgery. 

PMID- 26213288
TI  - Development of a chronic inhalation reference value for hexamethylenediamine
      using an exposure model based on the dihydrochloride salt.
AB  - The Texas Commission on Environmental Quality has developed a chronic inhalation
      Reference Value (ReV) for hexamethylenediamine (HMDA, CAS 124-09-4) based on
      respiratory effects identified in an animal study. HMDA is used in the fiber and
      plastics industry as an intermediate in the production of nylon, high-strength
      resins and polyamide adhesives. As a toxicant, HMDA acts primarily as a
      respiratory irritant with effects occurring in the upper respiratory tract,
      although systemic effects have been noted at higher concentrations. ReVs are
      chemical-specific air concentrations derived to protect human health. Acute and
      chronic ReVs were developed for HDMA based on an inhalation study conducted by
      the National Toxicology Program (NTP), which used the salt of HMDA,
      hexamethylenediamine dihydrochloride (HDDC, CAS 6055-52-3). For the chronic
      evaluation, rats and mice were exposed to 0, 1.6, 5, 16, 50 and 160 mg HDDC/m(3)
      for 13 weeks. The critical effect identified for the most sensitive species was
      hyaline degeneration in the olfactory epithelium in mice. The data provided in
      this study were suitable to benchmark concentration (BMC) modeling. Dosimetric
      adjustments using the rat and mouse Multiple-Path Particle Dosimetry Model
      (version 3.0) were made to the 95% lower limit of the BMC(10) to determine the
      human equivalent point of departure. Uncertainty factors were applied to account
      for variation in sensitivity within the human population, toxicodynamic
      differences between mice and humans, and use of a subchronic study. The ReV was
      initially calculated for HDDC and then adjusted for HMDA. The chronic ReV is 1.8
      ug/m(3) for respirable HMDA <= 10 um in diameter.

PMID- 26213290
TI  - On the True Indium Content of In-Filled Skutterudites.
AB  - The incongruently melting single-filled skutterudite InxCo4Sb12 is known as a
      promising bulk thermoelectric material. However, the products of current bulk
      syntheses contain always impurities of InSb, Sb, CoSb, or CoSb2, which prevent an
      unbiased determination of its thermoelectric properties. We report a new two-step
      synthesis of high-purity InxCo4Sb12 with nominal compositions x = 0.12, 0.15,
      0.18, and 0.20 that separates the kieftite (CoSb3) formation from the topotactic
      filler insertion. This approach allows conducting the reactions at lower
      temperatures with shorter reaction times and circumventing the formation of
      impurity phases. The synthesis can be extended to other filled skutterudites.
      High-density (>98%) pellets for thermoelectric characterization were prepared by
      current-assisted short-time sintering. Sample homogeneity was demonstrated by
      potential and Seebeck microprobe measurements of the complete pellet surfaces.
      Synchrotron X-ray diffraction showed a purity of 99.9% product with traces
      (<=0.1%) of InSb in samples of nominal composition In0.18Co4Sb12 and
      In0.20Co4Sb12. Rietveld refinements revealed a linear correlation between the
      true In occupancy and the lattice parameter a. This allows the determination of
      the true In filling in skutterudites and predicting the In content of unknown
      AxCo4Sb12. The high purity of InxCo4Sb12 allowed studying the transport
      properties without bias from side phases. A figure of merit close to unity at 420
      degrees C was obtained for a sample of a true composition of In0.160(2)Co4Sb12
      (nominal composition In0.18Co4Sb12). The lower degree of In filling has a
      dramatic effect on the thermoelectric properties as demonstrated by the sample of
      nominal composition In0.20Co4Sb12. The presence of InSb in amounts of ~0.1 vol%
      led to a substantially lower degree of interstitial site filling of 0.144, and
      the figure of merit zT decreased by 18%, which demonstrates the significance of
      the true filler atom content in skutterudite materials. 

PMID- 26213289
TI  - Hypereosinophilic syndrome: an indolent rash with a serious cardiac complication.
AB  - Idiopathic hypereosinophilic syndrome (HES) is a rare disorder, characterized by
      prominent blood or tissue eosinophilia with ensuing tissue damage, which is
      diagnosed after exclusion of underlying diseases known to cause HES. Sustained
      eosinophilia is associated with cardiac disease, including endomyocardial
      thrombosis and fibrosis, leading to restrictive cardiomyopathy, valvular
      dysfunction and increased thrombotic tendency. Aneurysmal coronary artery disease
      (CAD) occurring in the absence of stenotic atherosclerotic plaques is extremely
      rare. We present a case of idiopathic HES in a 30-year-old woman with
      asymptomatic multianeurysmal CAD and a sinus of Valsalva aneurysm, and discuss a
      brief review of the literature and management strategies.

PMID- 26213291
TI  - Low-Intensity Ultrasound Promotes Clathrin-Dependent Endocytosis for Drug
      Penetration into Tumor Cells.
AB  - Ultrasound-mediated drug delivery is a field of research with promising results,
      although the exact mechanisms underlying intracellular delivery of therapeutic
      compounds remain to be elucidated. Many studies use drug carriers and cavitation
      to enhance drug uptake into tumor cells. However, cavitation could induce cell
      lysis and remain difficult to control and predict in vivo. In this study, low
      intensity ultrasound was delivered using two transducers working at 2.9 and 1.3
      MHz. The maximal peak negative pressure was 0.29 MPa to avoid cavitation. Low
      intensity ultrasound induced clathrin-mediated endocytosis and forced the
      penetration of a bisphosphonate (zoledronic acid) into MCF-7 human breast cancer
      cells potentially as a result of mechanical stresses. When sonication parameters
      were adjusted to create mild hyperthermia in addition to the mechanical stress,
      further significant accumulation of ZOL was observed. These results provide
      better insight into the role of acoustic parameters in drug uptake.

PMID- 26213292
TI  - Molecular mapping of five soybean genes involved in male-sterility, female
      sterility.
AB  - In soybean, asynaptic and desynaptic mutants lead to abnormal meiosis and
      fertility reduction. Several male-sterile, female-sterile mutants have been
      identified and studied in soybean, however, some of these mutants have not been
      mapped to locations on soybean chromosomes. The objectives of this study were to
      molecularly map five male-sterile, female-sterile genes (st2, st4, st5, st6, and
      st7) in soybean and compare the map locations of these genes with already mapped
      sterility genes. Microsatellite markers were used in bulked segregant analyses to
      locate all five male-sterile, female-sterile genes to soybean chromosomes, and
      markers from the corresponding chromosomes were used on F2 populations to
      generate genetic linkage maps. The st2, st4, st5, st6, and st7 genes were located
      on molecular linkage group (MLG) B1 (chromosome 11), MLG D1a (chromosome 01), MLG
      F (chromosome 13), MLG B2 (chromosome 14), and D1b (chromosome 02), respectively.
      The st2, st4, st5, st6, and st7 genes were flanked to 10.3 (~ 399 kb), 6.3 (~ 164
      kb), 3.9 (~ 11.8 Mb), 11.0 (~ 409 kb), and 5.3 cM (~ 224 kb), and the flanked
      regions contained 57, 17, 362, 52, and 17 predicted genes, respectively. Future
      characterization of candidate genes should facilitate identification of the male-
      and female-fertility genes, which may provide vital insights on structure and
      function of genes involved in the reproductive pathway in soybean.

PMID- 26213293
TI  - Novel intracellular N-terminal truncated matrix metalloproteinase-2 isoform in
      skeletal muscle ischemia-reperfusion injury.
AB  - Ischemia-reperfusion injury (IRI) occurs when blood returns to tissues following
      a period of ischemia. Reintroduction of blood flow results in the production of
      free radicals and reactive oxygen species that damage cells. Skeletal muscle IRI
      is commonly seen in orthopedic trauma patients. Experimental studies in other
      organ systems have elucidated the importance of extracellular and intracellular
      matrix metalloproteinase-2 (MMP-2) isoforms in regulating tissue damage in the
      setting of oxidant stress resulting from IRI. Although the extracellular full
      length isoform of MMP-2 (FL-MMP-2) has been previously studied in the setting of
      skeletal muscle IRI, studies investigating the role of the N-terminal truncated
      isoform (NTT-MMP-2) in this setting are lacking. In this study, we first
      demonstrated significant increases in FL- and NTT-MMP-2 gene expression in C2C12
      myoblast cells responding to re-oxygenation following hypoxia in vitro. We then
      evaluated the expression of FL- and NTT-MMP-2 in modulating skeletal muscle IRI
      using a previously validated murine model. NTT-MMP-2, but not FL-MMP-2 expression
      was significantly increased in skeletal muscle following IRI. Moreover, the
      expression of toll-like receptors (TLRs) -2 and -4, IL-6, OAS-1A, and CXCL1 was
      also significantly up-regulated following IRI. Treatment with the potent anti
      oxidant pyrrolidine dithiocarbamate (PDTC) significantly suppressed NTT-MMP-2,
      but not FL-MMP-2 expression and improved muscle viability following IRI. This
      data suggests that NTT-MMP-2, but not FL-MMP-2, is the major isoform of MMP-2
      involved in skeletal muscle IRI.

PMID- 26213295
TI  - Reducing Cardiovascular Disease Globally: The World Heart Federation's Roadmaps.

PMID- 26213294
TI  - Recent progress and open questions in Drosophila dosage compensation.
AB  - Sexual dimorphism is observed in many traits across diverse taxa, and often it is
      quite extreme. Within a species, individuals of opposing sex can appear
      strikingly different, reflecting differences at the molecular level that may be
      similarly striking. Among the most extreme cases of such molecular sexual
      dimorphism is the quantity of sex chromosomes that each sex possesses. Hemizygous
      sex chromosomes are common to many species, and various mechanisms have evolved
      to regulate transcriptional activity to ensure appropriate sex chromosome-to
      autosome gene expression stoichiometry. Among the most thoroughly investigated of
      these mechanisms is Drosophila melanogaster's male-specific lethal (MSL) complex
      mediated dosage compensation. In Drosophila, the male X chromosome transcription
      is upregulated approximately two-fold in somatic tissues to counterbalance the
      effects of sex chromosome hemizygosity on transcript abundance. Despite dramatic
      advances in our understanding of the Drosophila dosage compensation, many
      questions remain unanswered, and our understanding of its molecular underpinnings
      remains incomplete. In this review, we synthesize recent progress in the field as
      a means to highlight open questions, including how the MSL complex targets the X
      chromosome, how dosage compensation has shaped evolution of X-linked genes, and
      the degree to which MSL complex-mediated dosage compensation varies in activity
      across somatic tissues. 

PMID- 26213296
TI  - Reducing Premature Cardiovascular Mortality By 2025: The World Heart Federation
      Roadmap.

PMID- 26213297
TI  - Reducing Premature Cardiovascular Morbidity and Mortality in People With
      Atherosclerotic Vascular Disease: The World Heart Federation Roadmap for
      Secondary Prevention of Cardiovascular Disease.

PMID- 26213298
TI  - Reducing Cardiovascular Mortality Through Prevention and Management of Raised
      Blood Pressure: A World Heart Federation Roadmap.

PMID- 26213299
TI  - Reducing Cardiovascular Mortality Through Tobacco Control: A World Heart
      Federation Roadmap.

PMID- 26213300
TI  - Adapting the World Heart Federation Roadmaps at the National Level: Next Steps
      and Conclusions.

PMID- 26213301
TI  - [A retinal hamartoma].

PMID- 26213302
TI  - [Establishment of a normative database for retinal nerve fiber layer thickness in
      a Lebanese population].

PMID- 26213303
TI  - [Progressive essential iris atrophy associated with angioid streaks].

PMID- 26213304
TI  - [Trichofolliculoma of the eyelid].

PMID- 26213305
TI  - In vivo analysis of the time and spatial activation pattern of microglia in the
      retina following laser-induced choroidal neovascularization.
AB  - Microglia play a major role in retinal neovascularization and degeneration and
      are thus potential targets for therapeutic intervention. In vivo assessment of
      microglia behavior in disease models can provide important information to
      understand patho-mechanisms and develop therapeutic strategies. Although scanning
      laser ophthalmoscope (SLO) permits the monitoring of microglia in transgenic mice
      with microglia-specific GFP expression, there are fundamental limitations in
      reliable identification and quantification of activated cells. Therefore, we
      aimed to improve the SLO-based analysis of microglia using enhanced image
      processing with subsequent testing in laser-induced neovascularization (CNV). CNV
      was induced by argon laser in MacGreen mice. Microglia was visualized in vivo by
      SLO in the fundus auto-fluorescence (FAF) mode and verified ex vivo using retinal
      preparations. Three image processing algorithms based on different analysis of
      sequences of images were tested. The amount of recorded frames was limiting the
      effectiveness of the different algorithms. Best results from short recordings
      were obtained with a pixel averaging algorithm, further used to quantify spatial
      and temporal distribution of activated microglia in CNV. Morphologically,
      different microglia populations were detected in the inner and outer retinal
      layers. In CNV, the peak of microglia activation occurred in the inner layer at
      day 4 after laser, lacking an acute reaction. Besides, the spatial distribution
      of the activation changed by the time over the inner retina. No significant time
      and spatial changes were observed in the outer layer. An increase in laser power
      did not increase number of activated microglia. The SLO, in conjunction with
      enhanced image processing, is suitable for in vivo quantification of microglia
      activation. This surprisingly revealed that laser damage at the outer retina led
      to more reactive microglia in the inner retina, shedding light upon a new
      perspective to approach the immune response in the retina in vivo. 

PMID- 26213306
TI  - Upregulation of sodium iodide symporter (NIS) protein expression by an innate
      immunity component: Promising potential for targeting radiosensitive
      retinoblastoma.
AB  - Retinoblastoma (RB), a malignant tumour of the eye arising from developing
      retina, is the most frequent primary intraocular malignancy of childhood. Its
      primary management with chemotherapy involves combination regimen of etoposide,
      vincristine and carboplatin and intra vitreal chemotherapy using melphalan when
      vitreous seeds develop. Radiotherapy is another effective mode in treating RB. We
      recently explored the notion if radiotherapy in RB can be mediated via Sodium
      Iodide Symporter (NIS), an intrinsic membrane glycoprotein which is a key
      regulator of iodide access to thyroid gland. Its expression has been exploited
      successfully for diagnostic imaging and molecular radionuclide-based therapy of
      thyroid cancer. We determined that NIS is expressed endogenously in RB tumour
      tissues, and in retinoblastoma cell lines Y79 and Weri-Rb-1, and therefore made
      an attempt to enhance the endogenously low expression of NIS protein in both Y79
      and Weri-Rb-1 cells. Here we report about the potential of bovine lactoferrin
      (bLf) which is a known chemo preventive and emerging safe anti-cancer bio drug,
      as well as a natural transcriptional activator of genes, to enhance the
      endogenous expression of NIS in Y79 and Weri-Rb-1 cells. Real time PCR revealed
      that both cell lines express mRNA of lactoferrin receptors while flow cytometry
      and confocal microscopy showed the cells efficiently internalize bLf which
      upregulates NIS expression. These findings highlight an important step that could
      be taken towards the development of less harmful approaches for the treatment of
      RB by employing natural supplement bLf (with its clinically proven safe profile),
      and warrants further studies in future, focussing on enhancing NIS expression in
      RB cells and NIS functional assays in these cells. 

PMID- 26213307
TI  - Beneficial protective effect of pramipexole on light-induced retinal damage in
      mice.
AB  - We investigated the effects of pramipexole, a potent dopamine receptor D2/D3
      agonist, on light-induced retinal damage in mice, H2O2-induced retinal pigment
      epithelium ARPE-19 cell injury in humans, and hydroxyl radical scavenging
      activity in a cell-free system. Pramipexole (0.1 and 1 mg/kg body weight) was
      orally administered to mice 1 h before light exposure (5000 lux, 2 h).
      Electrophysiological and morphologic studies were performed to evaluate the
      effects of the pramipexole on light-induced retinal damage in mice. Pramipexole
      significantly prevented the reduction of the a- and b-wave electroretinogram
      (ERG) amplitudes caused by light exposure in a dose-dependent manner. In
      parallel, damage to the inner and outer segments (IS/OS) of the photoreceptors,
      loss of photoreceptor nuclei, and the number of Tdt-mediated dUTP nick-end
      labeling (TUNEL)-positive cells in the outer nuclear layer (ONL) caused by light
      exposure were notably ameliorated by pramipexole. Additionally, pramipexole
      suppressed H2O2-induced ARPE-19 cell death in vitro in a concentration-dependent
      manner. The effect of pramipexole was significant at concentrations of 10(-6) M
      or higher. Pramipexole also significantly prevented H2O2-induced activation of
      caspases-3/7 and the intracellular accumulation of reactive oxygen species (ROS)
      in a concentration-dependent manner ranging from 10(-5) to 10(-3) M. Furthermore,
      pramipexole increased the scavenging activity toward a hydroxyl radical generated
      from H2O2 in a Fenton reaction. Our results suggest that pramipexole protects
      against light-induced retinal damage as an antioxidant and that it may be a novel
      and effective therapy for retinal degenerative disorders, such as dry age-related
      macular degeneration. 

PMID- 26213308
TI  - Interpreting mosaicism in chorionic villi: results of a monocentric series of
      1001 mosaics in chorionic villi with follow-up amniocentesis.
AB  - OBJECTIVES: Chromosomal mosaicism in chorionic villi (CV) is detected in ~1-2% of
      cases. When a mosaic in CV is detected during prenatal diagnosis, a confirmatory
      karyotype should be performed on amniocytes to discriminate between a mosaic
      confined to the placenta [confined placental mosaicism (CPM)] and one generalized
      to the fetus [true fetal mosaicism (TFM)]. We determined the likelihood that any
      mosaic abnormalities identified through CV samples are confirmed in the fetus.
      METHODS: Over a period of 14 years, the laboratory analyzed both the
      cytotrophoblast and the mesenchyme of 60 347 CV samples. Cytogenetic results from
      CV samples showing mosaicism with follow-up amniocentesis were considered. The
      incidence of CPM and TFM and the risk of confirmation in the amniotic fluid (AF)
      were calculated. Uniparental disomy (UPD) was tested on ~300 cases at risk due to
      involvement of an imprinted chromosome. RESULTS: Overall, 1317 mosaic CV cases
      (2.18%) were detected, of which 1001 were subsequently investigated by
      amniocentesis. The overall risk of TFM was 13% and UPD incidence was 2.1%.
      CONCLUSIONS: The very large presented sample set and consistency in cytogenetic
      methodology, especially the analysis of both placental layers performed on all CV
      samples will enable genetic counselors to determine the risk of fetal involvement
      and the clinical relevance of an identified mosaic condition.

PMID- 26213309
TI  - Brief report: enhancement of patient recruitment in rheumatoid arthritis clinical
      trials using a multi-biomarker disease activity score as an inclusion criterion.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) clinical trials often exclude patients who
      have low C-reactive protein (CRP) levels, which slows enrollment into the trial.
      The purpose of this study was to determine whether high Multi-Biomarker Disease
      Activity (MBDA) scores (>44) in RA patients with low CRP levels (<=10 mg/liter)
      could be used as a complement to CRP levels >10 mg/liter to enhance patient
      recruitment without affecting clinical trial outcomes. METHODS: We evaluated
      patients from the Swedish Pharmacotherapy (SWEFOT) trial, which did not include
      any selection criteria for CRP levels. Clinical outcomes were assessed after 3
      months of methotrexate (MTX) monotherapy in MTX-naive RA patients (n = 220) and
      after 3-10 months of add-on therapy in patients who were incomplete responders to
      MTX alone (MTX-IR) (n = 127). Radiographic outcomes were assessed at 1 year in
      all patients. Within each cohort, the outcomes were compared between patients
      with a CRP level of <=10 mg/liter and an MBDA score of >44 at the start of the
      respective treatment interval versus those with a CRP level of >10 mg/liter.
      RESULTS: Patients with both a CRP level of <=10 mg/liter and an MBDA score of >44
      at baseline had clinical and radiographic outcomes that were comparable to those
      in patients with a CRP level of >10 mg/liter at baseline. This broadened
      definition of the inclusion criteria identified an additional 24% of patients in
      the MTX-naive cohort and 47% in the MTX-IR cohort. CONCLUSION: Patient
      recruitment into RA clinical trials may be substantially enhanced, without any
      decrease in clinical and radiographic outcomes, by using as an inclusion
      criterion "a CRP level of >10 mg/liter and/or an MBDA score of >44."

PMID- 26213310
TI  - The need for radiotherapy in Europe in 2020: Not only data but also a cancer
      plan.
AB  - BACKGROUND: Planning radiation oncology equipment and staffing is necessary in
      public healthcare systems in Europe. METHODS: Three different data inputs were
      considered: evidence-based indications for radiotherapy, the incidence of cancer,
      and the stage at diagnosis of each cancer type, both the latter using population
      based data from cancer registries. The availability of these data and the
      implications for the estimation of the proportion of new cancer patients who
      would need radiotherapy treatment at least once during the course of the disease
      is reviewed. RESULTS: Depending on the frequency of cancers and the stage at
      diagnosis, it has been estimated that between 47% and 53% of incident cases among
      European countries would require external beam radiotherapy. When the actual data
      of utilization is compared with the evidence-based target, only one country in
      Europe has achieved full coverage. CONCLUSION: It is argued that these should be
      considered the optimal proportions of cancer patients, but a more realistic
      policy target could be set at 80% or higher of the optimal proportion. This
      realistic target also takes into account the inherent uncertainties in the
      assessment of evidence, and other factors that influence clinical decision-making
      in cases of multi-morbidity or patient preferences. Other factors are associated
      with problems that should be dealt with in the framework of a cancer plan, such
      as accessibility, preference bias in physician evaluation of the indication or
      shortage of resources, and the impact of the reimbursement system. Finally, it is
      argued that a cancer plan is the framework for achieving policy targets in the
      appropriate coverage of the evidence-based indications for radiation oncology
      forecasts.

PMID- 26213311
TI  - Dose painting by numbers in a standard treatment planning system using inverted
      dose prescription maps.
AB  - BACKGROUND: Dose painting by numbers (DPBN) is a method to deliver an
      inhomogeneous tumor dose voxel-by-voxel with a prescription based on biological
      medical images. However, planning of DPBN is not supported by commercial
      treatment planning systems (TPS) today. Here, a straightforward method for DPBN
      with a standard TPS is presented. MATERIAL AND METHODS: DPBN tumor dose
      prescription maps were generated from (18)F-FDG-PET images applying a linear
      relationship between image voxel value and dose. An inverted DPBN prescription
      map was created and imported into a standard TPS where it was defined as a mock
      pre-treated dose. Using inverse optimization for the summed dose, a planned DPBN
      dose distribution was created. The procedure was tested in standard TPS for three
      different tumor cases; cervix, lung and head and neck. The treatment plans were
      compared to the prescribed DPBN dose distribution by three-dimensional (3D) gamma
      analysis and quality factors (QFs). Delivery of the DPBN plans was assessed with
      portal dosimetry (PD). RESULTS: Maximum tumor doses of 149%, 140% and 151%
      relative to the minimum tumor dose were prescribed for the cervix, lung and head
      and neck case, respectively. DPBN distributions were well achieved within the
      tumor whilst normal tissue doses were within constraints. Generally, high gamma
      pass rates (> 89% at 2%/2 mm) and low QFs (< 2.6%) were found. PD showed that all
      DPBN plans could be successfully delivered. CONCLUSIONS: The presented
      methodology enables the use of currently available TPSs for DPBN planning and
      delivery and may therefore pave the way for clinical implementation.

PMID- 26213312
TI  - A learning programme qualifying radiation therapists to manage daily online
      adaptive radiotherapy.

PMID- 26213313
TI  - Imaging of tumour hypoxia and metabolism in patients with head and neck squamous
      cell carcinoma.
AB  - BACKGROUND: Tumour hypoxia and a high tumour metabolism increase radioresistance
      in patients with head and neck squamous cell carcinoma (HNSCC). The aim of this
      study was to evaluate the correlation between hypoxia ([(18)F]HX4 PET) and
      glucose metabolism ([(18)F]FDG PET) molecular imaging. MATERIAL AND METHODS:
      [(18)F]HX4 and [(18)F]FDG PET/CT images of 20 HNSCC patients were acquired prior
      to (chemo)radiotherapy, in an immobilisation mask, with a median time interval of
      seven days (NCT01347281). Gross tumour volumes of the primary lesions (GTVprim)
      and pathological lymph nodes (GTVln) were included in the analysis. [(18)F]FDG
      PET/CT images were rigidly registered to the [(18)F]HX4 PET/CT images. The
      maximum and mean standardised uptake values (SUVmax, SUVmean) within both GTVs
      were determined. In addition, the overlap was compared between the [(18)F]HX4
      high volume ([(18)F]HX4 HV) with a tumour-to-muscle ratio > 1.4 and the
      [(18)F]FDG high volume ([(18)F]FDG HV) with an SUV > 50% of the SUVmax. We report
      the mean +/- standard deviation. RESULTS: PET/CT scans including 20 GTVprim and
      12 GTVln were analysed. There was a significant correlation between several
      [(18)F]FDG and [(18)F]HX4 parameters, the most pronounced being the correlation
      between [(18)F]FDG HV and [(18)F]HX4 HV (R = 0.93, p < 0.001). The fraction of
      the GTVprim with a high HX4 uptake (9 +/- 10%) was on average smaller than the
      FDG high fraction (51 +/- 26%; p < 0.001). In 65% (13/20) of the patients, the
      GTVprim was hypoxic. In four of these patients the [(18)F]HX4 HV was located
      within the [(18)F]FDG HV, whereas for the remaining nine GTVprim a partial
      mismatch was observed. In these nine tumours 25 +/- 21% (range 5-64%) of the HX4
      HV was located outside the FDG HV. CONCLUSIONS: There is a correlation between
      [(18)F]HX4 and [(18)F]FDG uptake parameters on a global tumour level. In the
      majority of lesions a partial mismatch between the [(18)F]HX4 and [(18)F]FDG high
      uptake volumes was observed, therefore [(18)F]FDG PET imaging cannot be used as a
      surrogate for hypoxia. [(18)F]HX4 PET provides complementary information to
      [(18)F]FDG PET imaging.

PMID- 26213314
TI  - Examining the profile of high-potency cannabis and its association with severity
      of cannabis dependence.
AB  - BACKGROUND: Cannabis use is decreasing in England and Wales, while demand for
      cannabis treatment in addiction services continues to rise. This could be partly
      due to an increased availability of high-potency cannabis. METHOD: Adults
      residing in the UK were questioned about their drug use, including three types of
      cannabis (high potency: skunk; low potency: other grass, resin). Cannabis types
      were profiled and examined for possible associations between frequency of use and
      (i) cannabis dependence, (ii) cannabis-related concerns. RESULTS: Frequent use of
      high-potency cannabis predicted a greater severity of dependence [days of skunk
      use per month: b = 0.254, 95% confidence interval (CI) 0.161-0.357, p < 0.001]
      and this effect became stronger as age decreased (b = -0.006, 95% CI -0.010 to 
      0.002, p = 0.004). By contrast, use of low-potency cannabis was not associated
      with dependence (days of other grass use per month: b = 0.020, 95% CI -0.029 to
      0.070, p = 0.436; days of resin use per month: b = 0.025, 95% CI -0.019 to 0.067,
      p = 0.245). Frequency of cannabis use (all types) did not predict severity of
      cannabis-related concerns. High-potency cannabis was clearly distinct from low
      potency varieties by its marked effects on memory and paranoia. It also produced
      the best high, was preferred, and most available. CONCLUSIONS: High-potency
      cannabis use is associated with an increased severity of dependence, especially
      in young people. Its profile is strongly defined by negative effects (memory,
      paranoia), but also positive characteristics (best high, preferred type), which
      may be important when considering clinical or public health interventions
      focusing on cannabis potency.

PMID- 26213315
TI  - Clearance Prediction of HIV Protease Inhibitors in Man: Role of Hepatic Uptake.
AB  - The aim of this work was to explore the contribution of the organic anion
      transporting polypeptide-1B (OATP1B) drug transporters in the hepatic clearance
      (Cl) of all marketed HIV protease inhibitors (PI) in humans. HIV PI uptake rates
      in OATP1B1/1B3-transfected Chinese hamster ovary cells were converted to uptake
      Cl values in human hepatocytes via a relative activity factor, which was
      determined by comparing uptake of known substrates between OATP1B1/3-transfected
      cells and human hepatocytes. Metabolic Cl values were determined in human liver
      microsomes. In vivo hepatic Cl values were calculated either by combining drug
      uptake and metabolism or based on one of these individual Cl processes and
      compared with published in vivo hepatic Cl values. Excellent in vitro-in vivo
      correlation (R(2) = 0.85) was observed when only uptake Cl values were used, but
      not when only metabolic Cl was used (R(2) = 0.40). The correlation did not
      improve when both processes were taken into account (R(2) = 0.85). PBPK models
      confirmed the remarkable sensitivity of predicted exposure to hepatic drug
      uptake, indicating a key role for OATP1B1/3 in hepatic disposition of several HIV
      PI in man. This may contribute to the interindividual variability in systemic and
      hepatic exposure to these drugs in the clinic.

PMID- 26213316
TI  - Combined Rostrolateral Rhinotomy for Removal of Rostral Nasal Septum Squamous
      Cell Carcinoma: Long-Term Outcome in 10 Dogs.
AB  - OBJECTIVE: To report a surgical technique for combined rostrolateral rhinotomy
      (vestibulotomy) and long-term outcome for treatment of squamous cell carcinoma
      (SCC) of the rostral nasal septum in dogs. STUDY DESIGN: Retrospective case
      series. ANIMALS: Medium sized, mixed breed dogs (n = 10), aged 7-12.5 years, with
      SCC of the rostral nasal septum that did not invade the superficial nasal planum.
      METHODS: Disease extent was assessed with computed tomography and tumor resection
      achieved solely with central nasal planum elevation and lateral rhinotomy. Owners
      were interviewed 60-2,555 days (median, 548 days) postoperatively to determine
      outcome and survival time. RESULTS: Vestibulotomy facilitated full-thickness
      resection of the nasal septum and tumor mass in 10 dogs and nasal floor resection
      in 4 dogs. There were no major intraoperative complications and all dogs had an
      excellent cosmetic outcome. Tumor removal was complete in 8 dogs and incomplete
      in 2 dogs. There was no recurrence in 6 dogs. Of the 4 dogs with recurrence, 3
      had required nasal floor resection at initial surgery. CONCLUSIONS: A combined
      rostrolateral rhinotomy technique may be used to achieve complete resection of
      SCC limited to the nasal septum with acceptable cosmetic results. This technique
      may not be suitable for tumors extending into the nasal floor.

PMID- 26213317
TI  - Supporting women to achieve breastfeeding to six months postpartum - The
      theoretical foundations of a successful program.
AB  - BACKGROUND: Although the benefits of breastfeeding to six months are well
      established, only about half of Australian women succeed. The factors associated
      with successful breastfeeding are rarely translated into effective interventions.
      A new educational and support program, called the Milky Way program has been
      demonstrated to be effective in supporting women to achieve prolonged
      breastfeeding. In the Milky Way program, breastfeeding is considered an embodied
      performance which requires an engaged combination of body, mind and spirit. This
      paper aims to explain how the two theories that informed the program were used to
      better enable women's long term breastfeeding success. METHOD: The theory of self
      efficacy is first described as a way to develop women's cognitive processes to
      organise and execute the course of actions to breastfeed for a longer period of
      time. Birth territory theory is then presented. This theory discusses women as
      embodied selves; an essential concept for breastfeeding success. Birth territory
      theory also describes the effects of the holistic environment on the woman and
      explores the effects of power that is used in the environment. This power can be
      used integratively to strengthen the woman's breastfeeding confidence and success
      or, disintergratively which reduces her confidence and undermines her success.
      CONCLUSION: Strategies based on self-efficacy theory are helpful, but are not
      sufficient to promote breastfeeding to six months. Health educators also need to
      foster the woman's connection to, and trust in, her body and her baby's body to
      breastfeed spontaneously. Being aware of environmental impacts on how the woman
      and baby breastfeed; and using one's own power integratively is crucial to women
      being able to achieve prolonged breastfeeding.

PMID- 26213318
TI  - Surrogacy: The experience of Greek commissioning women.
AB  - BACKGROUND: Available studies on surrogacy are extremely limited. Findings
      suggest that surrogacy is experienced as problem free, with a significant number
      of commissioning mothers maintaining contact with the surrogates over time. AIM:
      To explore the experiences of Greek commissioning women regarding the surrogacy
      arrangement and birth of a child through surrogacy. METHODS: The data of this
      study were collected from 7 intended mothers who had either a long history of
      infertility or serious health problems. Interviews were tape-recorded,
      transcribed and analysed employing content analysis. FINDINGS: The analysis of
      the women's accounts revealed three themes: (a) a shared journey, (b) the birth
      of a long-awaited child, and (c) the surrogacy disclosure. The surrogacy process
      became the women's affairs, with their partners offering backstage support. A
      very close bond was developed with the surrogates, characterised by daily
      contacts and care-giving behaviours. While this bond was abruptly discontinued
      after the child's birth, it was interiorised with all participants being grateful
      to their surrogate. The timing and content of the surrogacy disclosure to family
      and child(ren) were carefully chosen by participants, who avoided providing
      information when egg donation was involved. CONCLUSION: Findings are reassuring
      for women who want to parent a child through a surrogate arrangement, and suggest
      that the availability of counselling services may help intended mothers to cope
      with disclosure issues.

PMID- 26213319
TI  - A Proof-of-Concept Case Study for Personalized Noninvasive Prenatal Diagnosis:
      Can We Put It to Work?
AB  - This commentary highlights the article by van den Oever et al that describes a
      new method of prenatal diagnosis of single-mutation disorders. 

PMID- 26213320
TI  - Dynamic Covalent Chemistry of Nucleophilic Substitution Component Exchange of
      Quaternary Ammonium Salts.
AB  - Dynamic covalent libraries (DCLs) of quaternary ammonium cations were set up by
      reversible nucleophilic substitution (S(N)2' and S(N)2) exchange reactions of
      ammonium salts and tertiary amines. The reactions were conducted at 60  degrees C
      to generate thermodynamically and kinetically controlled mixtures of quaternary
      ammonium compounds and tertiary amines, and were accelerated by using iodide as a
      nucleophilic catalyst. Microwave irradiation was used to assist the exchange
      reaction between the pyridinium salts and pyridine derivatives. Finally,
      experiments towards the generation of dynamic ionic liquids were performed. The
      results of this study pave the way for the extension of dynamic combinatorial
      chemistry to nucleophilic substitution reactions.

PMID- 26213321
TI  - TP53INP2/DOR protein chaperones deacetylated nuclear LC3 to the cytoplasm to
      promote macroautophagy.

PMID- 26213322
TI  - 1, 25(OH)2D3 protects beta cell against high glucose-induced apoptosis through
      mTOR suppressing.
AB  - Diabetes mellitus is a leading cause of death and disability worldwide, which
      presents a serious public health crisis in China nowadays. It has been well
      recognized that excessive beta-cell apoptosis is the key pathogenesis of
      diabetes, of which the mammalian target of rapamycin (mTOR) serves as the
      critical signaling pathway. Emerging evidence indicates that vitamin D deficiency
      acts as a potential risk factor for diabetes. The present study aims to test the
      hypothesis that 1 alpha, 25-dihydroxyvitamin D(3) [1, 25(OH)2D3] can inhibit beta
      cell apoptosis via the suppression of mTOR signaling pathway. beta-cells (INS-1)
      were cultured in the context of normal glucose or high glucose media with or
      without 1, 25(OH)2D3 treatment. beta-cell apoptosis was evaluated by inverted
      fluorescence microscope, flow cytometry and electron microscope, respectively.
      Quantitative RT-PCR and Western blotting were performed to assess the possible
      perturbations in mTOR signaling pathway. High glucose significantly increased
      beta-cell apoptosis. Of importance, RT-PCR and Western blotting demonstrated that
      high glucose inhibited DNA-damage-inducible transcript 4 (DDIT4) and TSC1/TSC2,
      up-regulated Rheb/mTOR/p70S6K and enhanced expression of the apoptosis regulating
      proteins, such as phospho-Bcl-2, cytochrome C and cleaved caspase. Interestingly,
      1, 25(OH)2D3 treatment reversed high glucose induced pathological changes in mTOR
      signaling pathway, restored expression of DDIT4 and TSC1/TSC2, blocked aberrant
      up-regulation of Rheb/mTOR/p70S6K and the apoptosis regulating proteins, and
      effectively inhibited beta-cell apoptosis. Therefore, 1, 25(OH)2D3 treatment can
      effectively protects beta cell against high glucose-induced apoptosis mainly via
      the suppression of mTOR signaling pathway, which may be considered as a potential
      therapy for patients with diabetes. 

PMID- 26213323
TI  - Orexins (hypocretins) and energy balance: More than feeding.
AB  - Initially implicated in the regulation of feeding, orexins/hypocretins are now
      acknowledged to play a major role in the control of a wide variety of biological
      processes, such as sleep, energy expenditure, pain, cardiovascular function and
      neuroendocrine regulation, a feature that makes them one of the most pleiotropic
      families of hypothalamic neuropeptides. While the orexigenic effect of orexins is
      well described, their central effects on energy expenditure and particularly on
      brown adipose tissue (BAT) thermogenesis are not totally unraveled. Better
      understanding of these actions and their possible interrelationship with other
      hypothalamic systems controlling thermogenesis, such as AMP-activated protein
      kinase (AMPK) and endoplasmic reticulum (ER) stress, will help to clarify the
      exact role and pathophysiological relevance of these neuropeptides have on energy
      balance. 

PMID- 26213324
TI  - HDAC inhibitor prevents LPS mediated inhibition of CYP19A1 expression and 17beta
      estradiol production in granulosa cells.
AB  - LPS inhibits CYP19A1 expression and 17beta-estradiol (E2) production in granulosa
      cells (GCs). This is one of the major causes of infertility underlying postpartum
      uterine infections. However, the precise molecular mechanism is not well
      elucidated. Recently we have shown, buffalo GCs exposed to LPS (1.0 MUg/ml) in
      serum free culture, transiently increased the pro-inflammatory cytokine genes (IL
      1beta, TNF-alpha, IL-6) expression, followed by the inhibition of CYP19A1
      expression and E2 production. The present study showed that transient increase in
      pro-inflammatory cytokines was associated with HDACs (gene expression and nuclear
      activity). Therefore, we tested the hypothesis if Trichostatin A (TSA), a HDAC
      inhibitor, can attenuate LPS induced pro-inflammatory cytokine gene expression
      and can prevent LPS mediated down-regulation of CYP19A1 expression and E2 in GCs.
      Results showed that TSA pre-treatment significantly attenuated LPS induced pro
      inflammatory cytokine gene expressions, HDACs (both gene expression and enzyme
      activity in nucleus) and NF-kappaB nuclear translocation. Additionally, TSA pre
      treatment reversed the inhibitory effect of LPS on CYP19A1 expression and E2
      production. CHIP analyses of H3 (Lys 9/14) acetylation of ovary specific CYP19A1
      proximal promoter (PII) showed that TSA pre-treatment prevented the LPS mediated
      H3 deacetylation, thereby increased the acetylation of PII and restored CYP19A1
      expression and E2 production. The present study demonstrated that TSA pre
      treatment attenuated- LPS induced immune response involving NF-kappaB and HDACs,
      and thus prevented inhibition of CYP19A1 expression and E2 production through
      chromatin remodeling. Our study suggests that HDAC inhibitors could be a
      potential therapeutic strategy to treat infertility underlying postpartum uterine
      infections. 

PMID- 26213325
TI  - Role of the AMP kinase in cytokine-induced human EndoC-betaH1 cell death.
AB  - The aim of the present investigation was to delineate cytokine-induced signaling
      and death using the EndoC-betaH1 cells as a model for primary human beta-cells.
      The cytokines IL-1beta and IFN-gamma induced a rapid and transient activation of
      NF-kappaB, STAT-1, ERK, JNK and eIF-2alpha signaling. The EndoC-betaH1 cells died
      rapidly when exposed to IL-1beta + IFN-gamma, and this occurred also in the
      presence of the actinomycin D. Inhibition of NF-kappaB and STAT-1 did not protect
      against cell death, nor did the cytokines activate iNOS expression. Instead,
      cytokines promoted a rapid decrease in EndoC-betaH1 cell respiration and ATP
      levels, and we observed protection by the AMPK activator AICAR against cytokine
      induced cell death. It is concluded that EndoC-betaH1 cell death can be prevented
      by AMPK activation, which suggests a role for ATP depletion in cytokine-induced
      human beta-cell death. 

PMID- 26213326
TI  - Coupling-Reagent-Free Synthesis of Dipeptides and Tripeptides Using Amino Acid
      Ionic Liquids.
AB  - A general method for the synthesis of dipeptides has been developed, which does
      not require any coupling reagents. This method is based on the reaction of
      readily available HCl salts of amino acid methyl esters with
      tetrabutylphosphonium amino acid ionic liquids. The isolation procedure of
      stepwise treatment with AcOH is easy to carry out. The method was extended to the
      synthesis of tripeptide, tyrosyl-glycyl-glycine, present in IMREG-1, also. 

PMID- 26213327
TI  - Interstitial 5-ALA photodynamic therapy and glioblastoma: Preclinical model
      development and preliminary results.
AB  - OBJECTIVE: Photodynamic therapy (PDT) has become a well-established modality for
      the treatment of many cancers. Photodynamic eradication of tumor cells depends on
      the presence of a photosensitizer, oxygen and light. However, oxygen depletion
      during PDT is a well known problem. Modulation of light delivery could address
      this issue by counteracting tumor hypoxia, thereby improving tumor cell killing.
      This preclinical study was designed to validate an animal model incorporating 5
      aminolaevulinic acid (5-ALA)-PDT using U87 glioblastoma cells. We aimed to
      evaluate the effects of light modulation for inducing specific tumoral lesions in
      this model (i.e., necrosis or apoptosis). MATERIALS AND METHODS: U87 glioblastoma
      cells were stereotactically engrafted into the brains of male fox1 rnu/rnu rats.
      Light delivery was studied after 5-ALA injection (100 mg/kg i.p.). 26J of 635 nm
      light was interstitially delivered to U87 tumor-bearing rats at a radiant power
      of either 30 mW (high fluence rate) or 4.8 mW (low fluence rate). In each group,
      half of the population received illumination in 2 fractions with a refractory
      interval of 120 s, whereas the other half received continuous illumination.
      RESULTS: Twenty-two animals received 5-ALA-PDT, and the level of necrosis was
      scored. In the high-fluence-rate group, we observed a greater degree of tumor
      necrosis in rats receiving fractionated delivery than in rats receiving
      continuous illumination. Similar differences were not observed in the low-fluence
      rate group, which exhibited only sparse necrosis. Higher morbidity and mortality
      rates were observed in the high-fluence-rate group. CONCLUSION: We have developed
      a reproducible and reliable rodent model for interstitial 5-ALA PDT. We found
      that the effects of 5-ALA-PDT are dependent on light delivery conditions.
      Although the low-fluence-rate treatment was better tolerated, 5-ALA-PDT induced
      more necrosis using fractionated delivery at a high fluence rate. These results
      require confirmation with further studies involving larger populations and
      additional fractionation schemes.

PMID- 26213328
TI  - Marijuana Use and Its Association with Participation, Navigation, and Enrollment
      in Health Research among African Americans.
AB  - This analysis examined the association between marijuana (Mj) use, willingness to
      participate, navigation and enrollment in health research among African
      Americans. Data from HealthStreet, a community-engagement model implemented in
      North Central Florida that reduces health disparities by engaging and linking
      community members to medical and social services and health research
      opportunities, were analyzed to determine willingness of African American Mj
      users to participate, be navigated to and enroll in health research studies.
      Among 1,496 African American community members, 8.0% were current Mj users, 30.3%
      were past Mj users and 61.7% reported never using Mj. Current and past Mj users
      were more willing to volunteer for a research study that only involved the use of
      medical records, required an overnight stay in a hospital or clinic, or might
      require use of medical equipment compared to those who never used Mj. Current Mj
      users were significantly less likely to be navigated (95% CI: 0.21-0.58) to
      health research studies while past Mj users (95% CI: 1.05-2.64) were
      significantly more likely to be enrolled in health research studies. Navigating
      and enrolling Mj users into health research studies could help decrease health
      disparities and increase health equity for the entire community since study
      findings would undoubtedly be more representative of the entire community rather
      than a select few. 

PMID- 26213330
TI  - Bad-good constraints on a polarity correspondence account for the spatial
      numerical association of response codes (SNARC) and markedness association of
      response codes (MARC) effects.
AB  - Performance in numerical classification tasks involving either parity or
      magnitude judgements is quicker when small numbers are mapped onto a left-sided
      response and large numbers onto a right-sided response than for the opposite
      mapping (i.e., the spatial-numerical association of response codes or SNARC
      effect). Recent research by Gevers et al. [Gevers, W., Santens, S., Dhooge, E.,
      Chen, Q., Van den Bossche, L., Fias, W., & Verguts, T. (2010). Verbal-spatial and
      visuospatial coding of number-space interactions. Journal of Experimental
      Psychology: General, 139, 180-190] suggests that this effect also arises for
      vocal "left" and "right" responding, indicating that verbal-spatial coding has a
      role to play in determining it. Another presumably verbal-based, spatial
      numerical mapping phenomenon is the linguistic markedness association of response
      codes (MARC) effect whereby responding in parity tasks is quicker when odd
      numbers are mapped onto left-sided responses and even numbers onto right-sided
      responses. A recent account of both the SNARC and MARC effects is based on the
      polarity correspondence principle [Proctor, R. W., & Cho, Y. S. (2006). Polarity
      correspondence: A general principle for performance of speeded binary
      classification tasks. Psychological Bulletin, 132, 416-442]. This account assumes
      that stimulus and response alternatives are coded along any number of dimensions
      in terms of - and + polarities with quicker responding when the polarity codes
      for the stimulus and the response correspond. In the present study, even-odd
      parity judgements were made using either "left" and "right" or "bad" and "good"
      vocal responses. Results indicated that a SNARC effect was indeed present for the
      former type of vocal responding, providing further evidence for the sufficiency
      of the verbal-spatial coding account for this effect. However, the decided lack
      of an analogous SNARC-like effect in the results for the latter type of vocal
      responding provides an important constraint on the presumed generality of the
      polarity correspondence account. On the other hand, the presence of robust MARC
      effects for "bad" and "good" but not "left" and "right" vocal responses is
      consistent with the view that such effects are due to conceptual associations
      between semantic codes for odd-even and bad-good (but not necessarily left
      right).

PMID- 26213329
TI  - Genetic, molecular and physiological basis of variation in Drosophila gut
      immunocompetence.
AB  - Gut immunocompetence involves immune, stress and regenerative processes. To
      investigate the determinants underlying inter-individual variation in gut
      immunocompetence, we perform enteric infection of 140 Drosophila lines with the
      entomopathogenic bacterium Pseudomonas entomophila and observe extensive
      variation in survival. Using genome-wide association analysis, we identify
      several novel immune modulators. Transcriptional profiling further shows that the
      intestinal molecular state differs between resistant and susceptible lines,
      already before infection, with one transcriptional module involving genes linked
      to reactive oxygen species (ROS) metabolism contributing to this difference. This
      genetic and molecular variation is physiologically manifested in lower ROS
      activity, lower susceptibility to ROS-inducing agent, faster pathogen clearance
      and higher stem cell activity in resistant versus susceptible lines. This study
      provides novel insights into the determinants underlying population-level
      variability in gut immunocompetence, revealing how relatively minor, but
      systematic genetic and transcriptional variation can mediate overt physiological
      differences that determine enteric infection susceptibility. 

PMID- 26213331
TI  - Ganoderma neo-japonicum Imazeki revisited: Domestication study and antioxidant
      properties of its basidiocarps and mycelia.
AB  - Mushroom cultivation benefits humankind as it deliberately encourages wild
      mushrooms to be commercially propagated while recycling agricultural wastes.
      Ganoderma neo-japonicum is a rare polypore mushroom found growing on decaying
      Schizostachyum brachycladium (a tropical bamboo) clumps in Malaysia. The
      Malaysian indigenous tribes including the Temuans and Temiars use the
      basidiocarps of G. neo-japonicum to treat various ailments including diabetes. In
      this study, the domestication of G. neo-japonicum in artificial logs of different
      agricultural residues was investigated. Sawdust promoted the mycelia spawn
      colonisation in the shortest period of 38 +/- 0.5 days. However, only sawdust and
      bamboo dust supported the primodia formation. Complex medium supported mycelium
      growth in submerged cultures and 27.11 +/- 0.43 g/L of mycelia was obtained after
      2 weeks of cultivation at 28  degrees C and 200 rpm. Antioxidant potential in
      mushroom may be influenced by different cultivation and extraction methods. The
      different extracts from the wild and cultivated basidiocarps as well as mycelia
      were then tested for their antioxidant properties. Aqueous and ethanol extracts
      of mycelia and basidiocarps tested had varying levels of antioxidant activities.
      To conclude, domestication of wild G. neo-japonicum using agroresidues may ensure
      a continuous supply of G. neo-japonicum for its medicinal use while ensuring the
      conservation of this rare species.

PMID- 26213332
TI  - Patient concern as a predictor of cutaneous malignancy.

PMID- 26213334
TI  - Right-but not left-paw use in female rats provides advantage in forced swim
      tests.
AB  - Left- and right-pawed adult female Wistar rats were subjected to forced swimming
      on two consecutive days. Compared to the right-pawed group, left- pawed rats
      displayed significantly increased immobility from the first to the second swim
      test and remained significantly more immobile in the second swim test. Both
      groups performed similarly in spatial learning in the Morris water maze
      suggesting that left- pawed rats are differentially and specifically susceptible
      to depressogenic treatment. 

PMID- 26213333
TI  - Progression from severe sepsis in pregnancy to death: a UK population-based case
      control analysis.
AB  - OBJECTIVE: To identify factors associated with progression from pregnancy
      associated severe sepsis to death in the UK. DESIGN: A population-based case
      control analysis using data from the UK Obstetric Surveillance System (UKOSS) and
      the UK Confidential Enquiry into Maternal Death (CEMD). SETTING: All pregnancy
      care and death settings in UK hospitals. POPULATION: All non-influenza sepsis
      related maternal deaths (January 2009 to December 2012) were included as cases (n
      = 43), and all women who survived severe non-influenza sepsis in pregnancy (June
      2011 to May 2012) were included as controls (n = 358). METHODS: Cases and
      controls were identified using the CEMD and UKOSS. Multivariable logistic
      regression was used to estimate adjusted odds ratios (aOR) with 95% confidence
      intervals. MAIN OUTCOME MEASURES: Odds ratios for socio-demographic, medical,
      obstetric and management factors in women who died from sepsis, compared with
      those who survived. RESULTS: Four factors were included in the final regression
      model. Women who died were more likely to have never received antibiotics [aOR =
      22.7, 95% confidence interval (CI) 3.64-141.6], to have medical comorbidities
      (aOR = 2.53, 95%CI 1.23-5.23) and to be multiparous (aOR = 3.57, 95%CI 1.62
      7.89). Anaemia (aOR = 13.5, 95%CI 3.17-57.6) and immunosuppression (aOR = 15.0,
      95%CI 1.93-116.9) were the two most important factors driving the association
      between medical comorbidities and progression to death. CONCLUSIONS: There must
      be continued vigilance for the risks of infection in pregnant women with medical
      comorbidities. Improved adherence to national guidelines, alongside prompt
      recognition and treatment with antibiotics, may reduce the burden from sepsis
      related maternal deaths. TWEETABLE ABSTRACT: Medical comorbidities, multiparity
      and antibiotic delays increase the risk of death from maternal sepsis.

PMID- 26213335
TI  - Are the carrot and the stick the two sides of same coin? A neural examination of
      approach/avoidance motivation during cognitive performance.
AB  - The present study examined neural circuit activity in a working memory (WM) task
      under conditions of approach and avoidance motivation. Eighteen participants were
      scanned with functional MRI while they performed a 3-back WM task under three
      conditions: in an avoidance condition incorrect responses were punished with
      monetary loss; in an approach condition correct responses were rewarded with
      monetary gain; in a neutral control condition there was no monetary incentive.
      Compared with the control condition, activation in fronto-parietal areas - which
      are associated with WM processing - was increased in both the approach and
      avoidance conditions. The results suggest that both approach and avoidance
      motivation increase task-related cognitive activation. 

PMID- 26213337
TI  - Socioecological factors and positive aspects of caregiving: findings from the
      REACH II intervention.
AB  - OBJECTIVE: Taking a socioecological perspective, this study assessed the
      relationship of intrapersonal, interpersonal, and organizational factors to
      positive aspects of caregiving (PAC) for 642 dementia caregivers by racial/ethnic
      group from the baseline data of the multisite Resources for Enhancing Alzheimer's
      Caregiver Health II (REACH II) intervention. METHODS: Nine intrapersonal
      indicators, 4 interpersonal indicators, and 12 organizational indicators were
      used. Blocked-multiple regression analyses by three racial/ethnic groups were
      computed to examine significant factors related to PAC among caregivers after
      controlling for memory and behavioral problems. RESULTS: Data showed a
      significant difference in PAC and significantly different indicators of PAC by
      racial/ethnic group. Hispanic caregivers reported the highest level of PAC while
      White participants showed the lowest scores on the measure of PAC. Education,
      marital status, and using formal transportation services were significant
      predictors for PAC among Hispanic caregivers; age, education, caregiving
      duration, and received social support were significant for PAC among African
      American caregivers; and sex, education, being a spousal caregiver, satisfaction
      with social support, using help from homemaker and visiting nurse services, and
      participating in support groups were significant among White caregivers.
      CONCLUSION: Findings indicate that PAC varies significantly across the three
      studied racial/ethnic groups of family caregivers and that intrapersonal,
      interpersonal, and organizational factors relate uniquely to PAC. Additional
      investigations of PAC could serve an important role in the development of family
      caregiving supports and services.

PMID- 26213336
TI  - Endothelial Jagged1 promotes solid tumor growth through both pro-angiogenic and
      angiocrine functions.
AB  - Angiogenesis is an essential process required for tumor growth and progression.
      The Notch signaling pathway has been identified as a key regulator of the neo
      angiogenic process. Jagged-1 (Jag1) is a Notch ligand required for embryonic and
      retinal vascular development, which direct contribution to the regulation of
      tumor angiogenesis remains to be fully characterized. The current study addresses
      the role of endothelial Jagged1-mediated Notch signaling in the context of
      tumoral angiogenesis in two different mouse tumor models: subcutaneous Lewis Lung
      Carcinoma (LLC) tumor transplants and the autochthonous Transgenic Adenocarcinoma
      of the Mouse Prostate (TRAMP). The role of endothelial Jagged1 in tumor growth
      and neo-angiogenesis was investigated with endothelial-specific Jag1 gain- and
      loss-of-function mouse mutants (eJag1OE and eJag1cKO). By modulating levels of
      endothelial Jag1, we observed that this ligand regulates tumor vessel density,
      branching, and perivascular maturation, thus affecting tumor vascular perfusion.
      The pro-angiogenic function is exerted by its ability to positively regulate
      levels of Vegfr-2 while negatively regulating Vegfr-1. Additionally, endothelial
      Jagged1 appears to exert an angiocrine function possibly by activating
      Notch3/Hey1 in tumor cells, promoting proliferation, survival and epithelial-to
      mesenchymal transition (EMT), potentiating tumor development. These findings
      provide valuable mechanistic insights into the role of endothelial Jagged1 in
      promoting solid tumor development and support the notion that it may constitute a
      promising target for cancer therapy. 

PMID- 26213339
TI  - Prevention of sporadic Alzheimer's disease: lessons learned from clinical trials
      and future directions.
AB  - Interventions that have even quite modest effects at the individual level could
      drastically reduce the future burden of dementia associated with Alzheimer's
      disease at the population level. In the past three decades, both pharmacological
      and lifestyle interventions have been studied for the prevention of cognitive
      decline or dementia in randomised controlled trials of individuals mostly aged
      older than 50-55 years with or without risk factors for Alzheimer's disease.
      Several trials testing the effects of physical activity, cognitive training, or
      antihypertensive interventions showed some evidence of efficacy on a primary
      cognitive endpoint. However, most of these trials had short follow-up periods,
      and further evidence is needed to confirm effectiveness and establish the optimum
      design or dose of interventions and ideal target populations. Important
      innovations in ongoing trials include the development of multidomain
      interventions, and the use of biomarker or genetic inclusion criteria. Challenges
      include the use of adaptive trial designs, the development of standardised,
      sensitive outcome measures, and the need for interventions that can be
      implemented in resource-poor settings. 

PMID- 26213338
TI  - The use of the acute Pd/Pa drop after intracoronary nitroglycerin infusion to
      rule out significant FFR: CANICA (Can intracoronary nitroglycerin predict
      fractional flow reserve without adenosine?) multicenter study.
AB  - OBJECTIVE: Functional assessment of coronary artery stenosis is performed by
      measuring the fractional flow reserve (FFR) under hyperemic conditions
      (Adenosine). However, the use of adenosine portends limitations. OBJECTIVE: We
      sought to investigate the relationship and correlation between FFR and the Pd/Pa
      value obtained just after the intracoronary infusion (acute drop) of
      nitroglycerin (Pd/Pa-NTG) and if this parameter enhances diagnostic accuracy for
      FFR prediction compared to the resting baseline Pd/Pa. METHODS: We conducted a
      multicenter study including prospectively patients presenting intermediate
      coronary artery stenosis (30-70%) evaluated with pressure wire. Resting baseline
      Pd/Pa, Pd/Pa-NTG and FFR were measured. RESULTS: 283 patients (335 lesions) were
      included. Resting baseline Pd/Pa value was 0.72 to 1.0 (0.93 +/- 0.04), Pd/Pa-NTG
      was 0.60 to 1.0 (0.87 +/- 0.07) and FFR 0.55 to 1.0 (0.83 +/- 0.08). The ROC
      curves for resting baseline Pd/Pa and for Pd/Pa-NTG, using a FFR <= 0.80 showed
      an AUC of 0.88 (95% CI: 0.84-0.92, P < 0.001) and 0.94 (95% CI: 0.92-0.96, P <
      0.001) respectively. The optimal cutoff values of resting baseline Pd/Pa and
      Pd/Pa-NTG for an FFR > 0.80, were >0.96 and >0.88, respectively. These values
      were present in a 29.8% (n = 100) and a 47.1% (n = 158), of the total lesions.
      Scatter plots showed a better correlation and agreement points with Pd/Pa-NTG
      than resting baseline Pd/Pa. The cutoff value of Pd/Pa-NTG > 0.88 showed an
      excellent NPV (96.2% for FFR > 0.8 and 100% for FFR > 0.75) and sensitivity (95%
      for FFR > 0.8 and 100% for FFR > 0.75) which were consistently high across all
      the subgroups analysis. CONCLUSION: The cutoff value of acute Pd/Pa-NTG > 0.88
      has a high NPV meaning adenosine-FFR can be avoided in almost half of lesions.

PMID- 26213341
TI  - Detrimental arterial inflammatory effect of microparticles circulating in
      preeclamptic women: ex vivo evaluation in human arteries.
AB  - Elevated plasmatic levels of lympho-monocyte and platelet microparticles (MPs)
      have been reported in preeclampsia. Previous studies suggest that MPs could
      participate in preeclampsia vascular impairment. In this study, we investigated
      the ex vivo vascular effects of MPs from preeclamptic women on arteries from
      normotensive pregnant women. Omental arteries were collected from normal pregnant
      women undergoing cesarean section and incubated during 24 h with MPs from normal
      pregnant or preeclamptic women. Vascular contraction to serotonin and
      phenylephrine was studied on a wire myograph with or without pharmacological
      selective inhibitors of inducible nitric oxide synthase (iNOS) and/or cyclo
      oxygenase-2 (COX-2). Expression of iNOS, COX-2, and NF-kappaB and production of
      superoxide anion and 8-isoprostane were also assessed by immunohistological or
      biochemical staining and/or Western blot or ELISA assay, respectively.
      Microparticles from preeclamptic women, but not those from normal pregnant women,
      induced hyporeactivity to vasocontracturant agonists in omental arteries.
      Selective inhibitor of iNOS partially restored this arterial contraction,
      suggesting that nitric oxide (NO) is involved in vascular contractility
      alteration. Conversely, COX-2 induced 8-isoprostane release, a vasoconstricting
      metabolite modulating the agonist-induced contraction. COX-2 selective inhibitor
      almost abolished the arterial contraction in the same vessels. Interestingly, the
      association of iNOS and COX-2 selective inhibitors restored the contraction to
      control levels. Moreover, iNOS, COX-2, and NF-kappaB expressions are upregulated
      and superoxide anion levels increased in vessels incubated with MPs from
      preeclamptic women. In conclusion, circulating MPs from preeclamptic women induce
      vascular inflammation and enhance oxidative stress. These results suggest a
      possible role of MPs during preeclampsia-induced arterial dysfunction.

PMID- 26213342
TI  - Parental socioeconomic status and prognosis in individuals with ultra-high risk
      for psychosis: A 2-year follow-up study.
AB  - A possible relationship between socioeconomic status (SES) and the development of
      mental illness has been continuously suggested. Still, less clear is whether the
      SES has a direct effect on the development of schizophrenia. In this longitudinal
      study, we test the hypothesis that parental SES is associated with the prognosis
      of individuals at ultra-high risk (UHR) for psychosis. One hundred and sixteen
      individuals who were determined as UHR using a Comprehensive Assessment of At
      Risk Mental States (CAARMS) were classified into three groups based on the
      parental SES levels assessed by the Hollingshead-Redlich scale. There were no
      differences in the Positive and Negative Syndrome Scale (PANSS), the Scale for
      the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of
      Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS) at
      baseline. However, at the 1-year follow-up, the higher versus lower SES group
      showed significant differences in clinical measures including SAPS, SANS, PANSS
      positive and negative scales as well as BPRS scores. Most of these clinical
      differences were attenuated by the second year of follow-up with no sign of an
      increased rate of conversion to psychosis derived from a socioeconomically
      disadvantaged status. However, SAPS and PANSS positive scale still revealed sub
      threshold positive symptoms within the low SES group at the 2-year follow-up.
      Moreover, especially for the subjects who continued the follow-ups for 1year
      and/or 2years, the changes of clinical symptoms between the baseline and follow
      ups showed that there were significant symptom changes in higher and middle SES
      groups within the 1-year period already, but the lower SES group showed
      significant recovery at the second year. Our findings suggest that low parental
      SES can be detrimental to the prognosis phase of individuals at UHR. Limited
      supportive socioeconomic resources may slow the rate of symptom recovery in UHR
      subjects. 

PMID- 26213343
TI  - Premorbid multivariate prediction of adult psychosis-spectrum disorder: A high
      risk prospective investigation.
AB  - Premorbid prediction of psychosis-spectrum disorders has implications for both
      understanding etiology and clinical identification. The current study used a
      longitudinal high-risk for psychosis design that included children of parents
      with schizophrenia as well as two groups of controls (children whose parents had
      no mental illness, and children with at least one parent with a non-psychotic
      psychiatric diagnosis). Premorbid neurological factors and an indication of
      social function, as measured when participants were 10-13years of age, were
      combined to predict psychosis-spectrum disorders in adulthood. Through a
      combination of childhood predictors, the model correctly classified 82% (27 of
      33) of the participants who eventually developed a psychosis-spectrum outcome in
      adulthood. With replication, multivariate premorbid prediction, including genetic
      risk, social, and neurological variables, could potentially be a useful
      complementary approach to identifying individuals at risk for developing
      psychosis-spectrum disorders. 

PMID- 26213344
TI  - Use of demographic and pharmacy data to identify patients included within both
      the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network
      (THIN).
AB  - PURPOSE: Pharmacoepidemiology researchers often utilize data from two UK
      electronic medical record databases, the Clinical Practice Research Datalink
      (CPRD) and The Health Improvement Network (THIN), and may choose to combine the
      two in an effort to increase sample size. To minimize duplication of data,
      previous studies examined the practice-level overlap between these databases.
      However, the proportion of overlapping patients remains unknown. We developed a
      method using demographic and pharmacy variables to identify patients included in
      both CPRD and THIN, and applied this method to measure the proportion of
      overlapping patients who initiated the oral anti-diabetic drug saxagliptin.
      METHODS: We conducted a cross-sectional study among patients initiating
      saxagliptin in CPRD and THIN between October 2009 and September 2012. Within both
      databases, we identified patients: (i) >=18 years, (ii) newly prescribed
      saxagliptin, and (iii) with >=180 days enrollment prior to saxagliptin
      initiation. Demographic data (birth year, sex, patient registration date, family
      number, and marital status) and prescriptions (including dates) for the first two
      oral anti-diabetic drugs prescribed within the study period were used to identify
      matching patients. RESULTS: Among 4202 CPRD and 3641 THIN patients initiating
      saxagliptin, 2574 overlapping patients (61% of CPRD saxagliptin initiators; 71%
      of THIN saxagliptin initiators) were identified. Among these patients, 2474
      patients (96%) perfectly matched on all demographic and prescription data.
      CONCLUSIONS: Within each database, over 60% of patients initiating saxagliptin
      were included within both CPRD and THIN. Combined demographic and prescription
      data can be used to identify patients included in both CPRD and THIN.

PMID- 26213345
TI  - Pushing the limits of neutral organic electron donors: a tetra(iminophosphorano)
      substituted bispyridinylidene.
AB  - A new ground-state organic electron donor has been prepared that features four
      strongly pi-donating iminophosphorano substituents on a bispyridinylidene
      skeleton. Cyclic voltammetry reveals a record redox potential of -1.70 V vs.
      saturated calomel electrode (SCE) for the couple involving the neutral organic
      donor and its dication. This highly reducing organic compound can be isolated (44
      %) or more conveniently generated in situ by a deprotonation reaction involving
      its readily prepared pyridinium ion precursor. This donor is able to reduce a
      variety of aryl halides, and, owing to its redox potential, was found to be the
      first organic donor to be effective in the thermally induced reductive S?N bond
      cleavage of N,N-dialkylsulfonamides, and reductive hydrodecyanation of
      malonitriles. 

PMID- 26213346
TI  - Semiconducting Graphene on Silicon from First-Principles Calculations.
AB  - Graphene is a semimetal with zero band gap, which makes it impossible to turn
      electric conduction off below a certain limit. Transformation of graphene into a
      semiconductor has attracted wide attention. Owing to compatibility with Si
      technology, graphene adsorbed on a Si substrate is particularly attractive for
      future applications. However, to date there is little theoretical work on band
      gap engineering in graphene and its integration with Si technology. Employing
      first-principles calculations, we study the electronic properties of monolayer
      and bilayer graphene adsorbed on clean and hydrogen (H)-passivated Si (111)/Si
      (100) surfaces. Our calculation shows that the interaction between monolayer
      graphene and a H-passivated Si surface is weak, with the band gap remaining
      negligible. For bilayer graphene adsorbed onto a H-passivated Si surface, the
      band gap opens up to 108 meV owing to asymmetry introduction. In contrast, the
      interaction between graphene and a clean Si surface is strong, leading to
      formation of chemical bonds and a large band gap of 272 meV. Our results provide
      guidance for device designs based on integrating graphene with Si technology. 

PMID- 26213347
TI  - PPAR-gamma agonist attenuates inflammation in aortic aneurysm patients.
AB  - BACKGROUND AND OBJECTIVE: Peroxisome proliferator-activated receptor (PPAR) 
      gamma agonist, which is an anti-diabetes drug and reduces expression of tumor
      necrosis factor (TNF)-alpha, reported to have the effects for anti-inflammation
      in our body. In cardiovascular fields, this PPAR-gamma agonist already reported
      to suppress progression of coronary atherosclerosis. Various cytokines, which is
      secreted from fat tissues around artery, promote atherosclerosis and/or
      aneurysmal changes in aorta/artery. Objective of our study is to clarify whether
      PPAR-gamma agonist has anti-inflammatory effects in aorta of patients with aortic
      aneurysm (AA). PATIENTS AND METHODS: The medical ethics committee in Tokushima
      University Hospital approved protocol for this study. Sixteen patients with AA
      (more than 5 cm in diameter, scheduled open surgery) were divided into two
      groups; one is PPAR-gamma agonist administrating group [Formula: see text] n = 6,
      group P[Formula: see text], and another is the without group [Formula: see text]
      n = 10, group C[Formula: see text]. PPAR-gamma agonist, whose dose was 15 mg/day,
      was administrated in the group P for more than 2 months before aneurysectomy and
      grafting (mean; 4.2 +/- 3.4 months) (Supplemental Table 1). Biopsy specimens were
      obtained from abdominal subcutaneous fat, greater omentum, retroperitoneal
      periaortic fat and aneurysmal wall in surgical procedure. Blood examination also
      achieved before/after procedure. Harvested specimens were analyzed with histology
      (HE and EVG), immunohistochemistry (macrophage) and RT-PCR (adiponectin, MCP-1,
      TNF-alpha, CD68, matrix metalloprotease (MMP)-2, MMP-9). RESULTS: Macrophage
      infiltration in aortic wall and retroperitoneal periaortic fat among group P was
      significantly decreased compared to that among group C. Adiponectin expressions
      in both subcutaneous fat and retroperitoneal periaortic fat among the group P
      (adiponectin/beta-actin) were significantly increased compared to those among the
      group C [subcutaneous fat; 16.8 +/- 13.9 vs. 5.82 +/- 2.94 (P = 0.04),
      retroperitoneal periaortic fat; 21.3 +/- 24.1 vs. 2.12 +/- 1.69 (P = 0.04)]. On
      the other hand, expressions of TNF-alpha, and MMP-9 in both aortic aneurysmal
      wall and retroperitoneal periaortic fat among group P were significantly
      decreased. [(Aortic aneurysmal wall; TNF-alpha; 0.45 +/- 0.15 vs. 5.18 +/- 3.49
      (P = 0.02), MMP-9; 39.6 +/- 69.0 vs. 721 +/- 741 (P = 0.04)], [retroperitoneal
      periaortic fat; TNF-alpha; 1.14 +/- 0.36 vs. 26.4 +/- 25.0 (P = 0.048), MMP-9;
      0.18 +/- 0.21 vs. 50.0 +/- 41.8 (P = 0.047)]. CONCLUSION: These data may indicate
      that PPAR-gamma agonist become the way for preventing or delaying aortic aneurysm
      progression in patients. More studies will be needed to clarify this drug effects
      in detail.

PMID- 26213348
TI  - Synapsin knockdown is associated with decreased neurite outgrowth, functional
      synaptogenesis impairment, and fast high-frequency neurotransmitter release.
AB  - Synapsins (Syns) are an evolutionarily conserved family of synaptic vesicle
      associated proteins related to fine tuning of synaptic transmission. Studies with
      mammals have partially clarified the different roles of Syns; however, the
      presence of different genes and isoforms and the development of compensatory
      mechanisms hinder accurate data interpretation. Here, we use a simple in vitro
      monosynaptic Helix neuron connection, reproducing an in vivo physiological
      connection as a reliable experimental model to investigate the effects of Syn
      knockdown. Cells overexpressing an antisense construct against Helix Syn showed a
      time-dependent decrease of Syn immunostaining, confirming protein loss. At the
      morphological level, Syn-silenced cells showed a reduction in neurite linear
      outgrowth and branching and in the size and number of synaptic varicosities.
      Functionally, Syn-silenced cells presented a reduced ability to form synaptic
      connections; however, functional chemical synapses showed similar basal
      excitatory postsynaptic potentials and similar short-term plasticity paradigms.
      In addition, Syn-silenced cells presented faster neurotransmitter release and
      decreased postsynaptic response toward the end of long tetanic presynaptic
      stimulations, probably related to an impairment of the synaptic vesicle
      trafficking resulting from a different vesicle handling, with an increased
      readily releasable pool and a compromised reserve pool.

PMID- 26213349
TI  - Gradient-based MCMC samplers for dynamic causal modelling.
AB  - In this technical note, we derive two MCMC (Markov chain Monte Carlo) samplers
      for dynamic causal models (DCMs). Specifically, we use (a) Hamiltonian MCMC (HMC
      E) where sampling is simulated using Hamilton's equation of motion and (b)
      Langevin Monte Carlo algorithm (LMC-R and LMC-E) that simulates the Langevin
      diffusion of samples using gradients either on a Euclidean (E) or on a Riemannian
      (R) manifold. While LMC-R requires minimal tuning, the implementation of HMC-E is
      heavily dependent on its tuning parameters. These parameters are therefore
      optimised by learning a Gaussian process model of the time-normalised sample
      correlation matrix. This allows one to formulate an objective function that
      balances tuning parameter exploration and exploitation, furnishing an
      intervention-free inference scheme. Using neural mass models (NMMs)-a class of
      biophysically motivated DCMs-we find that HMC-E is statistically more efficient
      than LMC-R (with a Riemannian metric); yet both gradient-based samplers are far
      superior to the random walk Metropolis algorithm, which proves inadequate to
      steer away from dynamical instability.

PMID- 26213350
TI  - Maturation of language networks in children: A systematic review of 22years of
      functional MRI.
AB  - Understanding how language networks change during childhood is important for
      theories of cognitive development and for identifying the neural causes of
      language impairment. Despite this, there is currently little systematic evidence
      regarding the typical developmental trajectory for language from the field of
      neuroimaging. We reviewed functional MRI (fMRI) studies published between 1992
      and 2014, and quantified the evidence for age-related changes in localisation and
      lateralisation of fMRI activation in the language network (excluding the
      cerebellum and subcortical regions). Although age-related changes differed
      according to task type and input modality, we identified four consistent findings
      concerning the typical maturation of the language system. First, activation in
      core semantic processing regions increases with age. Second, activation in lower
      level sensory and motor regions increases with age as activation in higher-level
      control regions reduces. We suggest that this reflects increased automaticity of
      language processing as children become more proficient. Third, the posterior
      cingulate cortex and precuneus (regions associated with the default mode network)
      show increasing attenuation across childhood and adolescence. Finally, language
      lateralisation is established by approximately 5years of age. Small increases in
      leftward lateralisation are observed in frontal regions, but these are tightly
      linked to performance. 

PMID- 26213351
TI  - Cytokine profile in drug-naive, first episode patients with psychosis.
AB  - OBJECTIVE: An increasing body of evidence suggests that immunological changes may
      play a role in schizophrenia but the results of the studies are controversial and
      little is known about the presence of those changes at the onset of the disease.
      Our aim is to compare the levels of interleukin (IL) IL-2, IL-6, IL-10, IL-17 and
      transforming growth factor -beta2 (TGF-beta2) between drug-naive-first episode
      patients with psychosis and healthy controls matched for age, sex, BMI and
      smoking. METHODS: Thirty-nine drug-naive-first episode patients with psychosis
      and 39 healthy individuals (control group) were enrolled in the study. Serum
      levels of IL-2, IL-6, IL-10, IL-17 and TGF-beta2 were measured by enzyme linked
      immunosorbent assay (ELISA). RESULTS: Serum IL-2 and IL-6 levels were
      significantly higher in the drug-naive patients with psychosis group (p<0.022 and
      p<0.002 respectively) compared to healthy controls. No differences were found
      between the two groups in the levels of IL-10, IL-17. The levels of TGF-beta2 did
      not differ significantly between the two groups. CONCLUSION: The serum levels of
      IL-2 and IL-6 are increased in first episode drug-naive patients with psychosis
      compared to healthy controls. An inflammatory response mediated by IL-2 and IL-6
      may play a role in schizophrenia.

PMID- 26213353
TI  - The skeletal manifestation of malaria: An epidemiological approach using
      documented skeletal collections.
AB  - OBJECTIVES: Recent studies in paleopathology have shown promise in associating
      some skeletal lesions with malarial infection. However, malaria's skeletal
      manifestation has never been confirmed using a large clinical reference sample
      from an endemic area for malaria with known individual causes of death. MATERIALS
      AND METHODS: To pinpoint evidence of malaria infection on ancient skeletal
      remains, this study uses an epidemiological approach to compare skeletal lesions
      in a modern reference sample of 98 individuals from Uganda, where malaria is
      holoendemic, to a similar modern sample of 106 individuals from a malaria-free
      area. RESULTS: Five porous skeletal lesions are identified that appear more
      frequently in the endemic area population, especially in anemic individuals.
      These appear on the cranium, vertebral column, and humeral and femoral necks.
      Periostitis also associates strongly with individuals in the endemic population;
      however, linear enamel hypoplasias show an inverse association. The identified
      lesions are tested for their association with each other, and then tested
      individually for their diagnostic power through measures of sensitivity and
      specificity. A diagnostic outcome algorithm is formed from the remaining skeletal
      lesions and their inter-lesion associations. DISCUSSION: Several etiological
      explanations for the characteristic malarial skeletal lesions are explored,
      including severe malarial anemia, an imbalance in bone remodeling, and
      extramedullary erythropoiesis. The importance of careful differential diagnoses
      between other infectious and noninfectious causes of these lesions is discussed,
      including the potential for coinfection of malaria with other infectious
      diseases. The findings of this study are pivotal in establishing diagnostic
      criteria by which we can identify the prevalence and impact of malaria on past
      populations.

PMID- 26213352
TI  - Do personality traits moderate the manifestation of type 2 diabetes genetic risk?
AB  - OBJECTIVE: To test whether personality traits moderate type 2 diabetes (T2D)
      genetic risk. METHODS: Using a large community-dwelling sample (n=837,
      Mage=69.59+/-0.85years, 49% males) we fitted a series of linear regression models
      predicting glycated haemoglobin (HbA1c) from T2D polygenic risk - aggregation of
      small individual effects of a large number of single nucleotide polymorphisms
      (SNPs) - and five personality traits. We tested the main effects of personality
      traits and their interactions with T2D polygenic risk score, controlling for age
      and sex. The models in the final set were adjusted for cognitive ability, highest
      educational qualification, and occupational class. RESULTS: Lower levels of
      openness were associated with heightened levels of HbA1c (beta=-0.014, p=.032).
      There was a significant interaction between T2D polygenic risk score and
      agreeableness: lower agreeableness was related to a stronger association between
      T2D polygenic risk and HbA1c (beta=-0.08, p=.021). In the model adjusted for
      cognitive ability, the main effect of openness was not significant (beta=-0.08,
      p=.057). The interaction between agreeableness and T2D polygenic risk was still
      present after controlling for cognitive ability and socioeconomic status
      indicators, and the interaction between conscientiousness and polygenic risk
      score was also significant: lower conscientiousness was associated with a
      stronger association between T2D polygenic risk and HbA1c levels (beta=0.09,
      p=.04). CONCLUSIONS: Personality may be associated with markers of diabetes, and
      may moderate the expression of its genetic risk.

PMID- 26213354
TI  - Novel LRRK2 mutations in Parkinsonism.

PMID- 26213355
TI  - Parallel damage in mitochondrial and lysosomal compartments promotes efficient
      cell death with autophagy: The case of the pentacyclic triterpenoids.
AB  - The role of autophagy in cell death is still controversial and a lot of debate
      has concerned the transition from its pro-survival to its pro-death roles. The
      similar structure of the triterpenoids Betulinic (BA) and Oleanolic (OA) acids
      allowed us to prove that this transition involves parallel damage in mitochondria
      and lysosome. After treating immortalized human skin keratinocytes (HaCaT) with
      either BA or OA, we evaluated cell viability, proliferation and mechanism of cell
      death, function and morphology of mitochondria and lysosomes, and the status of
      the autophagy flux. We also quantified the interactions of BA and OA with
      membrane mimics, both in-vitro and in-silico. Essentially, OA caused
      mitochondrial damage that relied on autophagy to rescue cellular homeostasis,
      which failed upon lysosomal inhibition by Chloroquine or Bafilomycin-A1. BA
      caused parallel damage on mitochondria and lysosome, turning autophagy into a
      destructive process. The higher cytotoxicity of BA correlated with its stronger
      efficiency in damaging membrane mimics. Based on these findings, we underlined
      the concept that autophagy will turn into a destructive outcome when there is
      parallel damage in mitochondrial and lysosomal membranes. We trust that this
      concept will help the development of new drugs against aggressive cancers. 

PMID- 26213356
TI  - The medial amygdaloid nucleus modulates the baroreflex activity in conscious
      rats.
AB  - The medial amygdaloid nucleus (MeA) is involved in cardiovascular control. In the
      present study we report the effect of MeA pharmacological ablations caused by
      bilateral microinjections of the nonselective synaptic blocker CoCl2 on cardiac
      baroreflex responses in rats. MeA synaptic inhibition evoked by local bilateral
      microinjection of 100 nL of CoCl2 (1 mM) did not affect blood pressure or heart
      rate baseline, suggesting no tonic MeA influence on resting cardiovascular
      parameters. However, 10 min after CoCl2 microinjection into the MeA of male
      Wistar rats, the reflex bradycardic response evoked by intravenous infusion of
      phenylephrine was significantly enhanced when compared with the reflex
      bradycardic response observed before CoCl2. The treatment did not affect the
      tachycardic responses to the intravenous infusion of sodium nitroprusside (SNP).
      Baroreflex activity returned to control values 60 min after CoCl2
      microinjections, confirming a reversible blockade. The present results indicate
      an involvement of the MeA in baroreflex modulation, suggesting that synapses in
      the MeA have an inhibitory influence on the bradycardic component of the
      baroreflex in conscious rats.

PMID- 26213357
TI  - Isoflurane causes concentration-dependent inhibition of medullary raphe 5-HT
      neurons in situ.
AB  - BACKGROUND: Anesthetics have a profound influence on a myriad of autonomic
      processes. Mechanisms of general anesthesia, and how these mechanisms give rise
      to the multifaceted state of anesthesia, are largely unknown. The ascending and
      descending serotonin (5-HT) networks are key modulators of autonomic pathways,
      and are critically involved in homeostatic reflexes across the motor,
      somatosensory, limbic and autonomic systems. These 5-HT networks are thought to
      contribute to anesthetic effects, but how anesthetics affect 5-HT neuron function
      remains a pertinent question. We hypothesized that the volatile anesthetic
      isoflurane inhibits action potential discharge of medullary raphe 5-HT neurons.
      METHODS: We conducted extracellular recordings on individual neurons in the
      medullary raphe region of the unanesthetized in situ perfused brainstem
      preparation to determine how exposure to isoflurane affects 5-HT neurons. We
      examined changes in 5-HT neuron baseline firing in response to treatment with
      either 1, 1.5, or 2% isoflurane. We measured isoflurane concentrations by gas
      chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Exposure to
      isoflurane inhibited action potential discharge in raphe 5-HT neurons. We
      document a concentration-dependent inhibition over a range of concentrations
      approximating isoflurane MAC (minimum alveolar concentration required for
      surgical anesthesia). Delivered concentrations of isoflurane were confirmed using
      GC-MS analysis. CONCLUSIONS: These findings illustrate that halogenated
      anesthetics greatly affect 5-HT neuron firing and suggest 5-HT neuron
      contributions to mechanisms of general anesthesia.

PMID- 26213358
TI  - Surgery in oesophago-gastric cancer with metastatic disease: Treatment, prognosis
      and preoperative patient selection.
AB  - BACKGROUND: The role of surgical resection in metastatic oesophago-gastric
      adenocarcinomas (EGA) is not defined and regularly discussed in interdisciplinary
      tumour boards. Primary objective of this retrospective study was the outcome of
      patients after surgery. We additionally evaluated our preoperative prognostic
      score (PPS) based on tumour grading, clinical response to chemotherapy and
      presumed R-status. METHODS: 123 of 811 EGA patients were evaluated as cM1, either
      confirmed intraoperatively or by imaging. Response evaluation after chemotherapy
      was performed by endoscopy, CT-scan and histopathologically. The prospectively
      documented patient and outcome data were analysed retrospectively. RESULTS: 70
      patients with adenocarcinoma of the oesophago-gastric junction and 53 patients
      with gastric cancer were included. The majority had one M1 site (n = 102). 72
      received preoperative chemotherapy (CTx) and 51 underwent primary resection. 11
      were explored without resection. 49/112 (40%) had multivisceral resections and
      63/112 (56%) were completely resected (R0). 26/72 (36%) were clinical responders
      and 30 patients had a favourable PPS. Median survival was 20.0 months. Survival
      was significantly prolonged by resection, especially complete resection, and by
      preoperative CTx (all p = 0.001). Multivisceral resection, type or number of
      metastases, or primary tumour localization had no impact on survival. In patients
      undergoing preoperative CTx, clinical response and the PPS influenced survival
      significantly. In R0 resected patients, preoperative CTx, clinical response and
      the PPS remained prognostic. CONCLUSION: Primary resection without preoperative
      CTx is not appropriate for metastatic EGA. Subgroups of patients with a
      favourable PPS with response to CTx may be good candidates for surgical resection
      in metastatic oesophago-gastric cancer.

PMID- 26213359
TI  - Inner workings of thrombolites: spatial gradients of metabolic activity as
      revealed by metatranscriptome profiling.
AB  - Microbialites are sedimentary deposits formed by the metabolic interactions of
      microbes and their environment. These lithifying microbial communities represent
      one of the oldest ecosystems on Earth, yet the molecular mechanisms underlying
      the function of these communities are poorly understood. In this study, we used
      comparative metagenomic and metatranscriptomic analyses to characterize the
      spatial organization of the thrombolites of Highborne Cay, The Bahamas, an
      actively forming microbialite system. At midday, there were differences in gene
      expression throughout the spatial profile of the thrombolitic mat with a high
      abundance of transcripts encoding genes required for photosynthesis, nitrogen
      fixation and exopolymeric substance production in the upper three mm of the mat.
      Transcripts associated with denitrification and sulfate reduction were in low
      abundance throughout the depth profile, suggesting these metabolisms were less
      active during midday. Comparative metagenomics of the Bahamian thrombolites with
      other known microbialite ecosystems from across the globe revealed that, despite
      many shared core pathways, the thrombolites represented genetically distinct
      communities. This study represents the first time the metatranscriptome of living
      microbialite has been characterized and offers a new molecular perspective on
      those microbial metabolisms, and their underlying genetic pathways, that
      influence the mechanisms of carbonate precipitation in lithifying microbial mat
      ecosystems. 

PMID- 26213360
TI  - Prognostic Effect of Ultra-Staging Node-Negative Colon Cancer Without Adjuvant
      Chemotherapy: A Prospective National Cancer Institute-Sponsored Clinical Trial.
AB  - BACKGROUND: We recently reported, in a prospective randomized trial, that ultra
      staging of patients with colon cancer is associated with significantly improved
      disease-free survival (DFS) compared with conventional staging. That trial did
      not control for lymph node (LN) number or adjuvant chemotherapy use. STUDY
      DESIGN: The current international prospective multicenter cooperative group trial
      (ClinicalTrials.gov identifier NCT00949312; "Ultra-staging in Early Colon
      Cancer") evaluates the 12-LN quality measure and nodal ultra-staging impact on
      DFS in patients not receiving adjuvant chemotherapy. Eligibility criteria
      included biopsy-proven colon adenocarcinoma; absence of metastatic disease; >12
      LNs staged pathologically; pan-cytokeratin immunohistochemistry (IHC) of
      hematoxylin and eosin (H&E)-negative LNs; and no adjuvant chemotherapy. RESULTS:
      Of 445 patients screened, 203 patients were eligible. The majority of patients
      had intermediate grade (57.7%) and T3 tumors (64.9%). At a mean follow-up of 36.8
      +/- 22.1 months (range 0 to 97 months), 94.3% remain disease free. Recurrence was
      least likely in patients with >=12 LNs, H&E-negative LNs, and IHC-negative LNs
      (pN0i-): 2.6% vs 16.7% in the pN0i+ group (p < 0.0001). CONCLUSIONS: This is the
      first prospective report to demonstrate that patients with optimally staged node
      negative colon cancer (>=12 LNs, pN0i-) are unlikely to benefit from adjuvant
      chemotherapy; 97% remain disease free after primary tumor resection. Both
      surgical and pathologic quality measures are imperative in planning clinical
      trials in nonmetastatic colon cancer.

PMID- 26213362
TI  - Assessment of the injection behavior of commercially available bone BSMs for
      Subchondroplasty(r) procedures.
AB  - BACKGROUND: Bone substitute materials (BSMs) have been commercially available for
      over 30 years and have been used extensively in orthopedic procedures. Some BSMs
      are described as "injectable." With rising focus on minimally invasive surgical
      procedures, the range of applications in which these materials are injectable is
      of clinical interest. Specifically, their performance in closed, pressurized
      environments in the trabecular bone with microdamage or abnormal bone remodeling
      have not been well characterized. This issue arises often in the presence of bone
      marrow lesions of the subchondral bone in early onset osteoarthritis. The
      objective was to evaluate the in vitro injectability of several common
      commercially available BSMs. It was hypothesized that some materials self
      described as "injectable" would fail to function in a small microarchitecture in
      comparison to the large void areas. METHODS: Mechanical testing was performed and
      force data was collected. Each sample was additionally radiographed and then
      imaged under micro-computed tomography (CT). RESULTS: Most of the BSM materials
      failed to be successfully injected into a simulated trabecular model. SimplexTM,
      AccuFill(r) and StrucSureTM materials were the only ones that were injected
      successfully. Many of the materials underwent phase separation at higher
      pressures and were not able to be deployed from the injection syringe. In
      addition, a clinically relevant difference was seen between the manners in which
      the materials interdigitated into the existing structure. CONCLUSION: The
      AccuFill(r) was the only material able to inject in a closed model and
      demonstrate adequate implantation of BSM into the simulated trabecular bone.
      CLINICAL RELEVANCE: Injectability of BSMs is clinically relevant as the interest
      in minimally invasive surgical procedures is rising rapidly.

PMID- 26213361
TI  - MRI-based analysis of patellofemoral cartilage contact, thickness, and alignment
      in extension, and during moderate and deep flexion.
AB  - BACKGROUND: Several factors are believed to contribute to patellofemoral joint
      function throughout knee flexion including patellofemoral (PF) kinematics,
      contact, and bone morphology. However, data evaluating the PF joint in this
      highly flexed state have been limited. Therefore, the purpose of this study was
      to evaluate patellofemoral contact and alignment in low (0 degrees ), moderate
      (60 degrees ), and deep (140 degrees ) knee flexion, and then correlate these
      parameters to each other, as well as to femoral morphology. METHODS: Sagittal
      magnetic resonance images were acquired on 14 healthy female adult knees (RSRB
      approved) using a 1.5 T scanner with the knee in full extension, mid-flexion, and
      deep flexion. The patellofemoral cartilage contact area, lateral contact
      displacement (LCD), cartilage thickness, and lateral patellar displacement (LPD)
      throughout flexion were defined. Intra- and inter-rater repeatability measures
      were determined. Correlations between patellofemoral contact parameters,
      alignment, and sulcus morphology were calculated. RESULTS: Measurement
      repeatability ICCs ranged from 0.94 to 0.99. Patellofemoral cartilage contact
      area and thickness, LCD, and LPD were statistically different throughout all
      levels of flexion (p<0.001). The cartilage contact area was correlated to LPD,
      cartilage thickness, sulcus angle, and epicondylar width (r=0.47-0.72, p<0.05).
      DISCUSSION: This study provides a comprehensive analysis of the patellofemoral
      joint throughout its range of motion. CONCLUSIONS: This study agrees with past
      studies that investigated patellofemoral measures at a single flexion angle, and
      provides new insights into the relationship between patellofemoral contact and
      alignment at multiple flexion angles. CLINICAL RELEVANCE: The study provides a
      detailed analysis of the patellofemoral joint in vivo, and demonstrates the
      feasibility of using standard clinical magnetic resonance imaging scanners to
      image the knee joint in deep flexion.

PMID- 26213363
TI  - Tuning Sodium Ion Conductivity in the Layered Honeycomb Oxide Na(3-x)Sn(2
      x)Sb(x)NaO6.
AB  - A series of compounds with the composition Na(3-x)Sn(2-x)Sb(x)NaO6 (x = 0.0, 0.2,
      0.4, 0.6, 0.7, 0.8, 0.9, and 1.0) has been prepared by solid-state reaction and
      characterized by powder X-ray diffraction, neutron diffraction (for x = 0.0), and
      impedance spectroscopy. The compounds have a layered structure derived from that
      of alpha-NaFeO2, with alternating Na3 planes and NaSn2O6 slabs with honeycomb in
      plane ordering. The structure of the parent compound, Na2SnO3, has been
      determined as a two-layer honeycomb in monoclinic space group C2/c. Due to charge
      neutrality requirements, the substitution of Sb(5+) for Sn(4+) creates sodium
      site vacancies that facilitate high sodium ion mobility. A decrease in layer
      stacking disorder is also observed. The conductivity increases linearly with x
      and has a maximum at x = 0.8 (1.43 * 10(-3) S/cm at 500  degrees C with
      suboptimal sample densities). This material may be of interest as a solid Na ion
      electrolyte.

PMID- 26213364
TI  - The Uro Dyna-CT Enables Three-dimensional Planned Laser-guided Complex Punctures.
AB  - BACKGROUND: Ultrasound and fluoroscopy are the standard imaging techniques used
      to perform punctures in urology. Cross-sectional and three-dimensional (3D)
      imaging may enable safer procedures, especially in complex cases. OBJECTIVES: To
      assess the feasibility of 3D planned laser-guided punctures in urology performed
      with the Uro Dyna-CT (Siemens Healthcare Solutions, Erlangen, Germany). DESIGN,
      SETTING, AND PARTICIPANTS: A total of 27 punctures using the laser-guided system
      syngo iGuide (Artis Zee Ceiling; Siemens Healthcare Solutions, Erlangen, Germany)
      for the Uro Dyna-CT have been performed to date. Patients with complex puncture
      indications due to unclear ultrasound findings or a suspicion of surrounding
      bowel were included. SURGICAL PROCEDURE: Image acquisition was performed using a
      customized 8s syngo iGuide protocol of the Uro Dyna-CT. The puncture tract was
      planned after 3D and cross-sectional image reconstruction. The puncture was
      performed supported by the laser-guiding system. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: The primary end point of our assessment was accuracy and
      applicability of the system in a clinical setting. Secondary end points were
      planning time, puncture time, and radiation exposure of the patient. RESULTS AND
      LIMITATIONS: Overall, 24 of 27 punctures were successful. No severe complications
      occurred. Median radiation dose of the Uro Dyna-CT scan was 6113.1 micrograys
      meter squared (MUGym(2); range: 1081.6-7957.2MUGym(2)). The small patient cohort
      is the major limitation of our study. CONCLUSIONS: We believe the Uro Dyna-CT
      based puncture technique is an excellent additional instrument that allows the
      urologist to handle complex punctures. Image acquisition leads to higher
      radiation doses than standard fluoroscopy but does not exceed the radiation
      exposure of alternative procedures such as computed tomography (CT)-guided
      punctures with multidetector CT, which is used mainly for complex cases. PATIENT
      SUMMARY: We report our experience with a three-dimensional planning and laser
      guiding tool to perform complex punctures for urologic indications. The technique
      is feasible in the endourologic intervention suite.

PMID- 26213365
TI  - Cadaveric anatomy in the future of medical education: What is the surgeons view?
AB  - Reduced contact hours and access to cadaveric/prosection-based teaching in
      medical education has led to many doctors reporting inadequate anatomical
      knowledge of junior doctors. This trend poses significant risk, but perhaps most
      of all in surgery. Here the opinions of surgeons regarding current and future
      teaching practices in anatomy were surveyed. Eighty surgeons were invited to
      complete a questionnaire, 48 of which were returned for a 60% response rate.
      Respondents were asked to select the method they viewed as the best method of
      teaching anatomy. Sixty-five percent of respondents selected "cadaver/prosection
      demonstration" (P < 0.001), while 55% of respondents, thought it should be
      enhanced in anatomy education (P < 0.001). Finally, respondents were asked to
      select what form of imaging should be further explored in anatomical education.
      Seventy-five percent of respondents' selected computerized tomography (CT)
      imaging compared to other imaging modalities (P < 0.001). These data show that
      surgeons view cadaveric/prosection-based teaching as the most beneficial method
      of teaching anatomy and that it should be enhanced in medical education.
      Furthermore, surgeons suggested that CT should be further integrated into
      anatomical education. These findings support the continued use of
      cadaveric/prosection-based teaching, and will help inform the integration of
      radiology in the design and implementation of anatomy teaching in medical
      education.

PMID- 26213366
TI  - Stabilization of intracellular trafficking and metabolism of amyloid beta-protein
      precursor and Alcadein beta by apolipoprotein E.
AB  - Intracellular metabolism of amyloid beta-protein precursor (APP) is important for
      the pathogenesis of Alzheimer's disease (AD). Alcadeins (Alcalpha, Alcbeta, and
      Alcgamma) are neural membrane proteins similar to APP in their localization,
      metabolism, and cellular function. Isoform epsilon4 of apolipoprotein E (ApoE) is
      a major risk factor for AD. We found that ApoE expression attenuated
      intracellular trafficking of APP and Alcbeta, resulting in metabolic
      stabilization of both proteins. By contrast, Alcalpha intracellular proteolysis
      was facilitated by ApoE expression, which was not due to an increase in the
      primary cleavage of Alcalpha. This difference may result from binding of ApoE to
      membrane proteins. 

PMID- 26213367
TI  - Human Mpn1 promotes post-transcriptional processing and stability of U6atac.
AB  - Mpn1 is an exoribonuclease that modifies the spliceosomal small nuclear RNA
      (snRNA) U6 by trimming its oligouridine tail and introducing a cyclic phosphate
      group (>p). Mpn1 deficiency induces U6 3' end misprocessing, accelerated U6 decay
      and pre-mRNA splicing defects. Mutations in the human MPN1 gene are associated
      with the genodermatosis Clericuzio-type poikiloderma with neutropenia (PN). Here
      we present the deep sequencing of the >p-containing transcriptomes of mpn1Delta
      fission yeast and PN cells. While in yeast U6 seems to be the only substrate of
      Mpn1, human Mpn1 also processes U6atac snRNA. PN cells bear unstable U6atac
      species with aberrantly long and oligoadenylated 3' ends. Our data corroborate
      the link between Mpn1 and snRNA stability suggesting that PN could derive from
      pre-mRNA splicing aberrations. 

PMID- 26213368
TI  - The adenosine triphosphate method as a quality control tool to assess
      'cleanliness' of frequently touched hospital surfaces.
AB  - BACKGROUND: The adenosine triphosphate (ATP) method is widely accepted as a
      quality control method to complement visual assessment, in the specifications of
      requirements, when purchasing cleaning contractors in Swedish hospitals. AIM: To
      examine whether the amount of biological load, as measured by ATP on frequently
      touched near-patient surfaces, had been reduced after an intervention; to
      evaluate the correlation between visual assessment and ATP levels on the same
      surfaces; to identify aspects of the performance of the ATP method as a tool in
      evaluating hospital cleanliness. METHODS: A prospective intervention study in
      three phases was carried out in a medical ward and an intensive care unit (ICU)
      at a regional hospital in mid-Sweden between 2012 and 2013. Existing cleaning
      procedures were defined and baseline tests were sampled by visual inspection and
      ATP measurements of ten frequently touched surfaces in patients' rooms before and
      after intervention. The intervention consisted of educating nursing staff about
      the importance of hospital cleaning and direct feedback of ATP levels before and
      after cleaning. FINDINGS: The mixed model showed a significant decrease in ATP
      levels after the intervention (P < 0.001). Relative light unit values were lower
      in the ICU. Cleanliness as judged by visual assessments improved. In the logistic
      regression analysis, there was a significant association between visual
      assessments and ATP levels. CONCLUSION: Direct feedback of ATP levels, together
      with education and introduction of written cleaning protocols, were effective
      tools to improve cleanliness. Visual assessment correlated with the level of ATP
      but the correlation was not absolute. The ATP method could serve as an
      educational tool for staff, but is not enough to assess hospital cleanliness in
      general as only a limited part of a large area is covered.

PMID- 26213369
TI  - Combination of serum miRNAs with Cyfra21-1 for the diagnosis of non-small cell
      lung cancer.
AB  - In this study, we screened 381 miRNAs by RT-qPCR in serum samples of 44 NSCLC
      patients and 22 healthy individuals to identify altered miRNAs, and validated the
      results in a training and test cohorts with 300 serum samples (178 NSCLC and 122
      healthy individuals). Three miRNAs (miR-194, miR-652 and miR-660) were selected
      from 380 miRNAs by two normalization methods in the discovery cohort, and miR-652
      and miR-660 were confirmed to be significantly upregulated in ADC and SCC
      patients compared with healthy controls both in the training and test cohorts (p
      < 0.01). The combination of miR-652 and miR-660 exhibited significantly higher
      AUC than miR-660, CEA and CA125 for ADC and SCC diagnosis in both the training
      and test cohorts (p < 0.05). Furthermore, miR-652 + miR-660 + Cyfra21-1
      significantly improved the diagnostic ability to determine ADC patients from
      healthy controls. For SCC diagnosis, miR-652 + miR-660 + Cyfra21-1 exhibited
      comparable ability to Cyfra21-1. The results indicate that the combination of miR
      652 + miR-660 and Cyfra21-1 has the potential to help in the diagnosis of NSCLC,
      especially for ADC. 

PMID- 26213370
TI  - Heterogeneity of liver cancer and personalized therapy.
AB  - Liver cancer is an extraordinarily heterogeneous malignant disease among the
      tumors that have so far been identified. Hepatocellular carcinoma (HCC) arises
      most frequently in the setting of chronic liver inflammation and fibrosis, and
      takes a variety of course in individual patients to process to tumor. The risk
      factors such as HBV and/or HCV infections, aflatoxin infection, abuse alcohol
      intake, metabolic syndrome, obesity and diabetes are closely related to the
      environmental and genetic susceptibilities to HCC. The consequent resulting
      genomic instability, molecular and signal transduction network disorders and
      microenvironmental discrepancies are characterized by the extraordinary
      heterogeneity of liver cancer. The histology-based definition of the
      morphological heterogeneity of liver cancer has been modified and refined to
      treat patients with targeted therapies, but this still cannot solve all the
      problems. Lack of consistent outcome for anticancer agents and conventional
      therapies in liver cancer treatment calls for assessing the benefits of new
      molecularly targeted drugs and combined therapy, under the heterogeneity
      condition of tumor. The present review article will provide the complex mechanism
      and phenotype of liver cancer heterogeneity, and help us to execute precision
      medicine in a really personalized manner.

PMID- 26213371
TI  - Control of crosslinking for tailoring collagen-based scaffolds stability and
      mechanics.
AB  - We provide evidence to show that the standard reactant concentrations used in
      tissue engineering to cross-link collagen-based scaffolds are up to 100 times
      higher than required for mechanical integrity in service, and stability against
      degradation in an aqueous environment. We demonstrate this with a detailed and
      systematic study by comparing scaffolds made from (a) collagen from two different
      suppliers, (b) gelatin (a partially denatured collagen) and (c) 50% collagen-50%
      gelatin mixtures. The materials were processed, using lyophilisation, to produce
      homogeneous, highly porous scaffolds with isotropic architectures and pore
      diameters ranging from 130 to 260 MUm. Scaffolds were cross-linked using a
      carbodiimide treatment, to establish the effect of the variations in crosslinking
      conditions (down to very low concentrations) on the morphology, swelling,
      degradation and mechanical properties of the scaffolds. Carbodiimide
      concentration of 11.5mg/ml was defined as the standard (100%) and was
      progressively diluted down to 0.1%. It was found that 10-fold reduction in the
      carbodiimide content led to the significant increase (almost 4-fold) in the
      amount of free amine groups (primarily on collagen lysine residues) without
      compromising mechanics and stability in water of all resultant scaffolds. The
      importance of this finding is that, by reducing cross-linking, the corresponding
      cell-reactive carboxylate anions (collagen glutamate or aspartate residues) that
      are essential for integrin-mediated binding remain intact. Indeed, a 10-fold
      reduction in carbodiimide crosslinking resulted in near native-like cell
      attachment to collagen scaffolds. We have demonstrated that controlling the
      degree of cross-linking, and hence retaining native scaffold chemistry, offers a
      major step forward in the biological performance of collagen- and gelatin-based
      tissue engineering scaffolds. STATEMENT OF SIGNIFICANCE: This work developed
      collagen and gelatine-based scaffolds with structural, material and biological
      properties suitable for use in myocardial tissue regeneration. The novelty and
      significance of this research consist in elucidating the effect of the
      composition, origin of collagen and crosslinking concentration on the scaffold
      physical and cell-binding characteristics. We demonstrate that the standard
      carbodiimide concentrations used to crosslink collagenous scaffolds are up to 100
      times higher than required for mechanical integrity in service, and stability
      against dissolution. The importance of this finding is that, by reducing
      crosslinking, the corresponding cell-reactive carboxylate anions (essential for
      integrin-mediated binding) remain intact and the native scaffold chemistry is
      retained. This offers a major step forward in the biological performance of
      tissue engineered scaffolds.

PMID- 26213373
TI  - Does incontinence precede pregnancy and delivery, or do pregnancy and delivery
      result in incontinence symptoms-and does it matter?

PMID- 26213372
TI  - Hydrogen sulfide enhances salt tolerance through nitric oxide-mediated
      maintenance of ion homeostasis in barley seedling roots.
AB  - Hydrogen sulfide (H2S) and nitric oxide (NO) are emerging as messenger molecules
      involved in the modulation of plant physiological processes. Here, we
      investigated a signalling network involving H2S and NO in salt tolerance pathway
      of barley. NaHS, a donor of H2S, at a low concentration of either 50 or 100 MUM,
      had significant rescue effects on the 150 mM NaCl-induced inhibition of plant
      growth and modulated the K(+)/Na(+) balance by decreasing the net K(+) efflux and
      increasing the gene expression of an inward-rectifying potassium channel (HvAKT1)
      and a high-affinity K(+) uptake system (HvHAK4). H2S and NO maintained the lower
      Na(+) content in the cytoplast by increasing the amount of PM H(+)-ATPase, the
      transcriptional levels of PM H(+)-ATPase (HvHA1) and Na(+)/H(+) antiporter
      (HvSOS1). H2S and NO modulated Na(+) compartmentation into the vacuoles with up
      regulation of the transcriptional levels of vacuolar Na(+)/H(+) antiporter
      (HvVNHX2) and H(+)-ATPase subunit beta (HvVHA-beta) and increased in the protein
      expression of vacuolar Na(+)/H(+) antiporter (NHE1). H2S mimicked the effect of
      sodium nitroprusside (SNP) by increasing NO production, whereas the function was
      quenched with the addition of NO scavenger. These results indicated that H2S
      increased salt tolerance by maintaining ion homeostasis, which were mediated by
      the NO signal. 

PMID- 26213374
TI  - Retinal nerve fiber layer and macular thickness in patients with schizophrenia:
      Influence of recent illness episodes.
AB  - Optical coherence tomography (OCT) has been recently used to investigate
      neuropsychiatric disorders. We aimed to study retinal OCT measures of patients
      with schizophrenia with respect to healthy controls, and to evaluate possible
      differences between recent illness episode (RIE) and non-recent illness episode
      (NRIE) patients. Thirty schizophrenia patients were classified as RIE (n=10) or
      NRIE (n=20), and compared with 30 matched controls. Statistical analyses included
      linear mixed-effects models to study the association between OCT measures and
      group membership. Multivariate models were used to control for potential
      confounders. In the adjusted linear mixed-effects regression model, patients had
      a significantly thinner retinal nerve fiber layer (RNFL) in overall measurements,
      and in the nasal, superior and inferior quadrants. Macular inner ring thickness
      and macular volume were also significantly smaller in patients than controls.
      Compared with controls, in the adjusted model only NRIE (but not RIE) patients
      had significantly reduced RNFL overall measures, superior RNFL, nasal RNFL,
      macular volume, and macular inner ring thickness. No significant correlation was
      found between illness duration and retinal measurements after controlling for
      age. In conclusion, retinal parameters observed using OCT in schizophrenia
      patients could be related to clinical status and merit attention as potential
      state biomarkers of the disorder. 

PMID- 26213375
TI  - Increased oxidative stress and oxidative DNA damage in non-remission
      schizophrenia patients.
AB  - Increasing evidence shows that oxidative stress plays a role in the
      pathophysiology of schizophrenia. But there is not any study which examines the
      effects of oxidative stress on DNA in schizophrenia patients. Therefore we aimed
      to assess the oxidative stress levels and oxidative DNA damage in schizophrenia
      patients with and without symptomatic remission. A total of 64 schizophrenia
      patients (38 with symptomatic remission and 26 without symptomatic remission) and
      80 healthy volunteers were included in the study. 8-hydroxydeoxyguanosine (8
      OHdG), total oxidant status (TOS) and total antioxidant status (TAS) were
      measured in plasma. TOS, oxidative stress index (OSI) and 8-OHdG levels were
      significantly higher in non-remission schizophrenic (Non-R-Sch) patients than in
      the controls. TOS and OSI levels were significantly higher in remission
      schizophrenic (R-Sch) patients than in the controls. TAS level were significantly
      lower and TOS and OSI levels were significantly higher in R-Sch patients than in
      Non-R-Sch patients. Despite the ongoing oxidative stress in patients with both R
      Sch and Non-R-Sch, oxidative DNA damage was higher in only Non-R-Sch patients
      compared to controls. It is suggested that oxidative stress can cause the disease
      via DNA damage, and oxidative stress plays a role in schizophrenia through
      oxidative DNA damage. 

PMID- 26213376
TI  - Associations between adult attachment style and mental health care utilization:
      Findings from a large-scale national survey.
AB  - This study investigated the association between attachment style and the use of a
      range of mental health services controlling socio-demographic, physical and
      psychological risk factors. Using a large nationally representative sample from
      the US National Comorbidity Survey Replication (NCS-R), a total of 5645
      participants (18+) were included. The majority of participants reported their
      attachment as secure (63.5%), followed by avoidant (22.2%), unclassified (8.8%),
      and anxious (5.5%). The percentages using different health services studied
      varied widely (1.1-31.1%). People with insecure (anxious and avoidant) attachment
      were more likely to report accessing a hotline, having had a session of
      psychological counselling or therapy, getting a prescription or medicine for
      mental and behavioural problems. Individuals with anxious attachment only were
      also more likely to report the use of internet support groups or chat rooms. This
      is a first analysis to explore relationships between self-reported adult
      attachment style and a wide range of health care services. Insecurely attached
      individuals were more likely to use a wide range of health care services even
      after controlling for socio-demographic factors, psychiatric disorders and
      chronic health conditions. These findings suggest that adult attachment plays an
      important role in the use of mental health care services. 

PMID- 26213377
TI  - Meta-analysis of dopamine receptor D1 rs4532 polymorphism and susceptibility to
      antipsychotic treatment response.
AB  - Previous association results between dopamine D1 receptor (DRD1) rs4532
      polymorphism and antipsychotic treatment response in schizophrenia and
      schizoaffective subjects have been conflicting. Thus, we have conducted a
      systematic review followed by a meta-analysis. Our results indicated no
      association between DRD1 rs4532 polymorphism and overall antipsychotic response
      or clozapine monotherapy response. 

PMID- 26213378
TI  - A meta-analysis of the response of pathological hoarding to pharmacotherapy.
AB  - This meta-analysis aimed to identify all studies that have assessed treatment
      response for pathological hoarding treated with pharmacological agents. Seven
      studies were identified with a total of 92 participants. Most participants had a
      diagnosis of obsessive-compulsive disorder. Studies assessed response to
      serotonin-reuptake inhibitors (SRIs); venlafaxine; methylphenidate; and
      augmentation of SRIs with quetiapine, minocycline and naltrexone. More than half
      (ER=0.58, 95% CI=0.37-0.76) of the participants treated with pharmacotherapy
      responded. This study encourages us to consider the use of SRIs in patients with
      hoarding disorder. The study also encourages more studies of pharmacotherapy for
      pathological hoarding, noting that these studies should use validated outcome
      measures that specifically assess pathological hoarding and novel agents that
      target the unique neurobiological correlates of pathological hoarding. 

PMID- 26213379
TI  - Diminishing the self-stigma of mental illness by coming out proud.
AB  - This randomized controlled trial examined the impact of the Coming Out Proud
      (COP) program on self-stigma, stigma stress, and depression. Research
      participants who experienced mental health challenges were randomly assigned to a
      three session COP program (n=51) or a waitlist control (n=75). Outcome measures
      that assessed the progressively harmful stages of self-stigma, stigma stress
      appraisals, and depression were administered at pre-test, post-test, and one
      month follow-up. People completing COP showed significant improvement at post
      test and follow-up in the more harmful aspects of self-stigma compared to the
      control group. COP participants also showed improvements in stigma stress
      appraisals. Women participating in COP showed significant post-test and follow-up
      reductions in depression after COP compared to the control group. Men did not
      show this effect. Future research should determine whether these benefits also
      enhance attitudes related to recovery, empowerment, and self-determination. 

PMID- 26213380
TI  - The relationship between personality disorder traits and reactive versus
      proactive motivation for aggression.
AB  - There is a strong link between personality disorders (PDs) and aggression. This
      is reflected in high prevalence rates of PD diagnoses in forensic samples, and in
      several diagnostic criteria of PDs directly referring to elevated levels of
      aggression. Aggression can stem from two distinct types of motivation; reactive
      or impulsive aggression that serves as a defensive reaction to provocation, and
      proactive or premeditated aggression used to gain extrinsic benefits. Although
      some clinical conditions like antisocial, borderline, and narcissistic PDs or PD
      traits, have been empirically linked to reactive and/or proactive aggression, the
      current study pioneers assessing the relationship between reactive and proactive
      aggression and traits of all 10 PDs. A mixed sample of patient and non-patient
      (N=238) participants were administered with the SCID II to assess the level of PD
      traits; they also completed the Reactive Proactive Questionnaire to determine
      levels of reactive and proactive aggression. Results showed that paranoid PD
      traits were positively related to reactive aggression, whereas proactive
      aggression was uniquely related to antisocial PD traits. This highlights the
      importance of differentiating between distinct motivations for aggression in PD
      samples. 

PMID- 26213381
TI  - Potency and penetration of telavancin in staphylococcal biofilms.
AB  - Due to the emergence of staphylococcal biofilm infections, the need for advanced
      antibiotics is crucial. The aim of this investigation was to evaluate the potency
      and penetration of telavancin against staphylococcal biofilms using two different
      biofilm models. Multiple staphylococcal strains, including meticillin-sensitive
      Staphylococcus aureus ATCC 29213, vancomycin-intermediate S. aureus ATCC 700787,
      heterogeneously vancomycin-intermediate S. aureus ATCC 700698 and meticillin
      sensitive Staphylococcus epidermidis ATCC 12228, were grown and treated in drip
      flow reactors to determine log reductions due to telavancin treatment. After 3
      days of biofilm growth and 24 h of treatment, mean log reductions for telavancin
      ranged from 1.65 to 2.17 depending on the bacterial strain tested. Penetration
      was evaluated qualitatively using confocal scanning laser microscopy to image the
      infiltration of fluorescently labelled antibiotic into a staphylococcal biofilm
      grown in a flow cell. Fluorescently labelled telavancin rapidly penetrated the
      biofilms with no alteration in the biofilm structure.

PMID- 26213382
TI  - Optimisation of the Caenorhabditis elegans model for studying the pathogenesis of
      opportunistic Acinetobacter baumannii.
AB  - This study aimed to increase the sensitivity of Caenorhabditis elegans as an
      infection model for detection of minor differences in virulence or fitness
      between different Acinetobacter baumannii strains with known resistance and
      virulence mechanisms. Selected A. baumannii strains and mutants, comprising wild
      type strains (ATCC 17978 and 19606), colistin-resistant strains (ATCC 19606
      DeltalpxA and ATCC 19606 DeltalpxC), a clinical encapsulated isolate (AB307
      0294), an imipenem-resistant strain (ATCC 17978 Deltaomp33-36) and an sRNA knock
      out strain (ATCC 17978 Delta13573), were employed in developing killing and
      fertility assays in a C. elegans infection model. Because virulence levels of the
      strains were known, they could be used to assess assays in the nematode model for
      their ability to discriminate between degrees of virulence. The model was
      validated by microscopic analysis and in a murine sepsis infection model. The
      fertility assay, specifically utilising nematode growth medium, was able to
      detect virulence differences between the wild-type strains, ATCC 19606 DeltalpxA
      and isolate AB307-0294. Moreover, modification of an alternative culture medium
      by incremental changes in osmolarity facilitated detection of subtle virulence
      differences between isogenic mutants (ATCC 17978 Deltaomp33-36 and 17978
      Delta13573). The success of the proposed fertility model depends on establishing
      a balance between optimal C. elegans reproduction and environmental stress
      leading to maximum pathogen-induced damage. This invertebrate model may reduce
      the need for mammalian in vivo studies of A. baumannii resistance and
      pathogenicity and may additionally be validated for the study of other low
      virulence bacterial pathogens.

PMID- 26213383
TI  - Cross-Generational Reproductive Fitness Enforced by Microchimeric Maternal Cells.
AB  - Exposure to maternal tissue during in utero development imprints tolerance to
      immunologically foreign non-inherited maternal antigens (NIMA) that persists into
      adulthood. The biological advantage of this tolerance, conserved across mammalian
      species, remains unclear. Here, we show maternal cells that establish
      microchimerism in female offspring during development promote systemic
      accumulation of immune suppressive regulatory T cells (Tregs) with NIMA
      specificity. NIMA-specific Tregs expand during pregnancies sired by males
      expressing alloantigens with overlapping NIMA specificity, thereby averting fetal
      wastage triggered by prenatal infection and non-infectious disruptions of fetal
      tolerance. Therefore, exposure to NIMA selectively enhances reproductive success
      in second-generation females carrying embryos with overlapping paternally
      inherited antigens. These findings demonstrate that genetic fitness, canonically
      thought to be restricted to Mendelian inheritance, is enhanced in female
      placental mammals through vertically transferred maternal cells that promote
      conservation of NIMA and enforce cross-generational reproductive benefits.

PMID- 26213384
TI  - beta-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid
      Signaling.
AB  - alpha- and beta-neurexins are presynaptic cell-adhesion molecules implicated in
      autism and schizophrenia. We find that, although beta-neurexins are expressed at
      much lower levels than alpha-neurexins, conditional knockout of beta-neurexins
      with continued expression of alpha-neurexins dramatically decreased
      neurotransmitter release at excitatory synapses in cultured cortical neurons. The
      beta-neurexin knockout phenotype was attenuated by CB1-receptor inhibition, which
      blocks presynaptic endocannabinoid signaling, or by 2-arachidonoylglycerol
      synthesis inhibition, which impairs postsynaptic endocannabinoid release. In
      synapses formed by CA1-region pyramidal neurons onto burst-firing subiculum
      neurons, presynaptic in vivo knockout of beta-neurexins aggravated
      endocannabinoid-mediated inhibition of synaptic transmission and blocked LTP;
      presynaptic CB1-receptor antagonists or postsynaptic 2-arachidonoylglycerol
      synthesis inhibition again reversed this block. Moreover, conditional knockout of
      beta-neurexins in CA1-region neurons impaired contextual fear memories. Thus, our
      data suggest that presynaptic beta-neurexins control synaptic strength in
      excitatory synapses by regulating postsynaptic 2-arachidonoylglycerol synthesis,
      revealing an unexpected role for beta-neurexins in the endocannabinoid-dependent
      regulation of neural circuits.

PMID- 26213385
TI  - ATF5 Connects the Pericentriolar Materials to the Proximal End of the Mother
      Centriole.
AB  - Although it is known that the centrioles play instructive roles in pericentriolar
      material (PCM) assembly and that the PCM is essential for proper centriole
      formation, the mechanism that governs centriole-PCM interaction is poorly
      understood. Here, we show that ATF5 forms a characteristic 9-fold symmetrical
      ring structure in the inner layer of the PCM outfitting the proximal end of the
      mother centriole. ATF5 controls the centriole-PCM interaction in a cell-cycle-
      and centriole-age-dependent manner. Interaction of ATF5 with polyglutamylated
      tubulin (PGT) on the mother centriole and with PCNT in the PCM renders ATF5 as a
      required molecule in mother centriole-directed PCM accumulation and in PCM
      dependent centriole formation. ATF5 depletion blocks PCM accumulation at the
      centrosome and causes fragmentation of centrioles, leading to the formation of
      multi-polar mitotic spindles and genomic instability. These data show that ATF5
      is an essential structural protein that is required for the interaction between
      the mother centriole and the PCM.

PMID- 26213386
TI  - Detection of the source of hemorrhage using postmortem computerized tomographic
      angiography in a case of a giant juvenile nasopharyngeal angiofibroma after
      surgical treatment.
AB  - PURPOSE: Postmortem computerized tomographic angiography (PMCTA) has been
      increasingly used in forensic medicine to detect and locate the source of
      bleeding in cases of fatal acute hemorrhage. In this paper, we report a case of
      postoperative complication in a patient with a giant juvenile nasopharyngeal
      angiofibroma in which the source of bleeding was detected by PMCTA. METHODS: A
      case description and evaluations of the pre- and postoperative exams, postmortem
      CT angiogram, and conventional autopsy results are provided. RESULTS: The source
      of bleeding was identified by postmortem CT angiography but not by conventional
      autopsy. The established protocol, injecting contrast medium into the femoral
      artery, was effective in identifying the source of bleeding. CONCLUSIONS:
      Postoperative bleeding is a rare and frequently fatal complication of juvenile
      nasopharyngeal angiofibroma. As a complement to conventional autopsy, postmortem
      angiography is a valuable tool for the detection of lethal acute hemorrhagic
      foci, and establishing a routine procedure for PMCTA may improve its efficiency.

PMID- 26213388
TI  - The Order of Knowing: Juan Luis Vives on Language, Thought, and the Topics.

PMID- 26213387
TI  - AVP-IC50 Pred: Multiple machine learning techniques-based prediction of peptide
      antiviral activity in terms of half maximal inhibitory concentration (IC50).
AB  - Peptide-based antiviral therapeutics has gradually paved their way into
      mainstream drug discovery research. Experimental determination of peptides'
      antiviral activity as expressed by their IC50 values involves a lot of effort.
      Therefore, we have developed "AVP-IC50 Pred," a regression-based algorithm to
      predict the antiviral activity in terms of IC50 values (MUM). A total of 759 non
      redundant peptides from AVPdb and HIPdb were divided into a training/test set
      having 683 peptides (T(683)) and a validation set with 76 independent peptides
      (V(76)) for evaluation. We utilized important peptide sequence features like
      amino-acid compositions, binary profile of N8-C8 residues, physicochemical
      properties and their hybrids. Four different machine learning techniques (MLTs)
      namely Support vector machine, Random Forest, Instance-based classifier, and K
      Star were employed. During 10-fold cross validation, we achieved maximum Pearson
      correlation coefficients (PCCs) of 0.66, 0.64, 0.56, 0.55, respectively, for the
      above MLTs using the best combination of feature sets. All the predictive models
      also performed well on the independent validation dataset and achieved maximum
      PCCs of 0.74, 0.68, 0.59, 0.57, respectively, on the best combination of feature
      sets. The AVP-IC50 Pred web server is anticipated to assist the researchers
      working on antiviral therapeutics by enabling them to computationally screen many
      compounds and focus experimental validation on the most promising set of
      peptides, thus reducing cost and time efforts. The server is available at
      http://crdd.osdd.net/servers/ic50avp.

PMID- 26213389
TI  - The Ageing of Information: From Particular to Particulate.

PMID- 26213393
TI  - "Science Organized": Positivism and the Metaphysical Club, 1865-1875.

PMID- 26213397
TI  - Community-Based Participatory Research Adds Value to the National Cancer
      Institute's Research Portfolio.

PMID- 26213398
TI  - A Legacy of Science and Community Engagement via the Community Networks Program.
AB  - This special issue documents the progress of a unique group of research
      investigations that further legitimize the engagement of affected communities in
      quality cancer health disparities research and, the importance of mentoring and
      training of new and diverse health disparity researchers. The implications for
      the reduction and elimination of cancer health disparities within the United
      States are apparent. The diversity of populations included in these novel studies
      also has implications for addressing inequities in a global context.

PMID- 26213400
TI  - Cancer Screening Utilization Among Immigrant Women in Miami, Florida.
AB  - BACKGROUND: Routine cancer screening for cervical, breast, and colorectal cancers
      reduces disease-associated morbidity and mortality through early detection and
      treatment. Lack of access to health care is a major barrier to screening in
      immigrant populations. OBJECTIVES: We aimed to characterize compliance with
      national cancer screening guidelines and to assess predictors of screening
      compliance among women residing in each of two distinct immigrant communities in
      Miami-Dade County--Little Haiti (Haitian) and Hialeah (Cuban). METHODS: Through a
      collaborative community-based participatory research (CBPR) initiative,
      researchers, key community stakeholders, and community members developed the
      study design. Data were collected from a total of 234 women via a rapid
      assessment survey administered by community health workers (CHWs). RESULTS:
      Compliance with national screening guidelines for breast, cervical, and
      colorectal screening was low in both community samples relative to national
      averages, and for cervical cancer screening was significantly lower in Little
      Haiti than Hialeah (p<.01). In addition, knowledge of cervical cancer etiology
      was significantly greater in Hialeah than in Little Haiti (p<.01). Health
      insurance and having a usual source of health care were significant correlates of
      cancer screening. CONCLUSION: Given the disparities in cancer screening between
      our samples and the larger sociodemographic groups in which they are often
      included, targeted approaches that address structural barriers (lack of health
      insurance or usual source of care) may improve access to cancer screening among
      recent immigrants. Community partnerships may be essential in facilitating the
      interventions needed to overcome cancer-related disparities in these groups.

PMID- 26213402
TI  - Shifting Community-Based Participatory Infrastructure from Education/Outreach to
      Research: Challenges and Solutions.
AB  - BACKGROUND: For 10 years, the Deep South Network for Cancer Control (DSNCC)
      focused on training and deploying community health advisors (CHAs) to promote
      cancer screening and healthy lifestyle through education/outreach activities. In
      2009, the request for application (RFA) for renewal of the DSNCC required a
      controlled research intervention. Converting from education/outreach to research
      proved more problematic than expected. OBJECTIVES: The objective of this article
      was to describe the challenges and solutions during this conversion and to
      describe the importance of education/outreach to community infrastructure.
      METHODS: This is a qualitative assessment of the challenges and solutions
      encountered in conducting a controlled weight loss trial in a community setting
      in which education/outreach had been the priority. LESSON LEARNED: The DSNCC
      provides a model for overcoming the unique challenges of converting a
      longstanding education/outreach program into a controlled research program.
      CONCLUSION: Although multiple challenges were encountered in conducting a
      community-based participatory research (CBPR) controlled trial, solutions were
      developed and the trial continues as proposed.

PMID- 26213401
TI  - The National Cancer Institute's Community Networks Program Initiative to Reduce
      Cancer Health Disparities: Outcomes and Lessons Learned.
AB  - BACKGROUND: We describe reach, partnerships, products, benefits, and lessons
      learned of the 25 Community Network Programs (CNPs) that applied community-based
      participatory research (CBPR) to reduce cancer health disparities. METHODS:
      Quantitative and qualitative data were abstracted from CNP final reports.
      Qualitative data were grouped by theme. RESULTS: Together, the 25 CNPs worked
      with more than 2,000 academic, clinical, community, government, faith-based, and
      other partners. They completed 211 needs assessments, leveraged funds for 328
      research and service projects, trained 719 new investigators, educated almost
      55,000 community members, and published 991 articles. Qualitative data
      illustrated how use of CBPR improved research methods and participation; improved
      knowledge, interventions, and outcomes; and built community capacity. Lessons
      learned related to the need for time to nurture partnerships and the need to
      attend to community demand for sustained improvements in cancer services.
      IMPLICATIONS: Findings demonstrate the value of government-supported, community
      academic, CBPR partnerships in cancer prevention and control research.

PMID- 26213403
TI  - Fulfilling Ethical Responsibility: Moving Beyond the Minimal Standards of
      Protecting Human Subjects from Research Harm.
AB  - PROBLEM: Rules for protecting human subjects, in place federally since 1974, have
      focused primarily on guarding against placing research subjects at social,
      physical, or psychological risk or violating their privacy and confidentiality.
      Nevertheless, high-risk communities are routinely subjected to "sins of
      omission," which limit access to potentially significant research opportunities
      and result in the absence of studies that could confer high degree of community
      beneficence. PURPOSE OF ARTICLE: To describe "sins of omission" and provide
      examples from the Community Networks Program Centers (CNPC) to illustrate how
      community-based participatory research (CBPR) can prevent them. KEY POINTS: CBPR
      is an effective antidote to sins of omission. Activities undertaken by the CNPCs
      illustrate how adherence to CBPR principles can improve research access and
      outcomes. CONCLUSIONS: By working with community members as partners, we expand
      the concept of beneficence to include "community beneficence," thus reducing the
      probability of "sins of omission."

PMID- 26213404
TI  - Introducing Biospecimen Science to Communities: Tools from Two Cities.
AB  - BACKGROUND: This article describes community-engaged processes employed by two
      Community Network Program Center (CNPC) sites located in Tampa, Florida, and
      Buffalo, New York, toward the development of Spanish/English educational products
      about biobanking and biospecimen research. METHODS: Each CNPC carried out a
      community-based participatory research (CBPR) approach that underscored six
      essential components that moved concepts to a final educational product in a
      highly participatory fashion. The similar CBPR processes at the two locations
      focused on the same topic, resulted in different engagement approaches and tools
      for their respective communities: 1) DVD and brochure toolkit and 2) PowerPoint,
      group program with audience response system (ARS). RESULTS: We detail a
      comparison of methods and applications for using these tools among diverse
      community groups to advance understandings about genetic and biomedical research
      technologies. CONCLUSION: Ultimately, these tools and associated educational
      efforts emphasize the critical value of co-learning among academic and community
      members in biobanking and biospecimen research.

PMID- 26213405
TI  - A Tale of Two Community Networks Program Centers: Operationalizing and Assessing
      CBPR Principles and Evaluating Partnership Outcomes.
AB  - BACKGROUND: Community Networks Program (CNP) centers are required to use a
      community-based participatory research (CBPR) approach within their specific
      priority communities. Not all communities are the same and unique contextual
      factors and collaborators' priorities shape each CBPR partnership. There are also
      established CBPR and community engagement (CE) principles shown to lead to
      quality CBPR in any community. However, operationalizing and assessing CBPR
      principles and partnership outcomes to understand the conditions and processes in
      CBPR that lead to achieving program and project level goals is relatively new in
      the science of CBPR. OBJECTIVES: We sought to describe the development of surveys
      on adherence to and implementation of CBPR/CE principles at two CNP centers and
      examine commonalities and differences in program-versus project-level CBPR
      evaluation. METHODS: A case study about the development and application of
      CBPR/CE principles for the Missouri CNP, Program for the Elimination of Cancer
      Disparities, and Minnesota CNP, Padres Informados/Jovenes Preparados, surveys was
      conducted to compare project versus program operationalization of principles.
      Survey participant demographics were provided by CNP. Specific domains found in
      CBPR/CE principles were identified and organized under an existing framework to
      establish a common ground. Operational definitions and the number of survey items
      were provided for each domain by CNP. CONCLUSION: There are distinct differences
      in operational definitions of CBPR/CE principles at the program and project
      levels of evaluation. However, commonalities support further research to develop
      standards for CBPR evaluation across partnerships and at the program and project
      levels.

PMID- 26213407
TI  - Targeting and Tailoring Health Communications in Breast Screening Interventions.
AB  - BACKGROUND: Members of underrepresented minority (URM) groups are at higher risk
      of disproportionately experiencing greater breast cancer-related morbidity and
      mortality and thus, require effective interventions that both appropriately
      target and tailor to their unique characteristics. OBJECTIVES: We sought to
      describe the targeting and tailoring practices used in the development and
      dissemination of three breast cancer screening interventions among URM groups.
      METHODS: Three national Community Network Programs (CNPs) funded by the National
      Cancer Institute have focused on breast cancer screening interventions as their
      major research intervention. Each targeted different populations and used
      participatory research methods to design their intervention tailored to the needs
      of their respective audience. The Alameda County Network Program (ACNP) to Reduce
      Cancer Disparities partnered with community members to design and conduct 2-hour
      "Tea Party" education sessions for Afghan women. The Kansas Community Cancer
      Disparities Network co-developed and deployed with community members a
      computerized Healthy Living Kansas (HLK) Breast Health program for rural Latina
      and American Indian women. The Johns Hopkins Center to Reduce Cancer Disparities
      employed a train-the-trainer COACH approach to educate urban African-American
      women about breast cancer. CONCLUSIONS: Each CNP program targeted diverse URM
      women and, using participatory approaches, tailored a range of interventions to
      promote breast cancer screening. Although all projects shared the same goal
      outcome, each program tailored their varying interventions to match the target
      community needs, demonstrating the importance and value of these strategies in
      reducing breast cancer disparities.

PMID- 26213406
TI  - Considering the Role of Stress in Populations of High-Risk, Underserved Community
      Networks Program Centers.
AB  - BACKGROUND: Cancer disparities are associated with a broad range of sociocultural
      determinants of health that operate in community contexts. High-risk populations
      may be more vulnerable to social and environmental factors that lead to chronic
      stress. Theoretical and empirical research indicates that exposure to contextual
      and sociocultural stress alters biological systems, thereby influencing cancer
      risk, progression, and, ultimately, mortality. OBJECTIVE: We sought to describe
      contextual pathways through which stress likely increases cancer risk in high
      risk, underserved populations. METHODS: This review presents a description of the
      link between contextual stressors and disease risk disparities within underserved
      communities, with a focus on 1) stress as a proximal link between biological
      processes, such as cytokine responses, inflammation, and cancer and 2) stress as
      a distal link to cancer through biobehavioral risk factors such as poor diet,
      physical inactivity, circadian rhythm or sleep disruption, and substance abuse.
      These concepts are illustrated through application to populations served by three
      National Cancer Institute-funded Community Networks Program Centers (CNPCs):
      African Americans in the Deep South (the South Carolina Cancer Disparities
      Community Network [SCCDCN]), Native Hawaiians ('Imi Hale-Native Hawaiian Cancer
      Network), and Latinos in the Lower Yakima Valley of Washington State (The Center
      for Hispanic Health Promotion: Reducing Cancer Disparities). CONCLUSIONS: Stress
      experienced by the underserved communities represented in the CNPCs is marked by
      social, biological, and behavioral pathways that increase cancer risk. A case is
      presented to increase research on sociocultural determinants of health, stress,
      and cancer risk among racial/ethnic minorities in underserved communities.

PMID- 26213411
TI  - [Lymphohematopoietic cancer among semiconductor-manufacturing workers in Korea].

PMID- 26213409
TI  - Mentoring and Training of Cancer-Related Health Disparities Researchers Committed
      to Community-Based Participatory Research.
AB  - BACKGROUND AND OBJECTIVE: The National Cancer Institute's (NCI) Community
      Networks Program Centers (CNPCs) provide community-based participatory research
      (CBPR)-oriented mentoring and training to prepare early-stage/midcareer
      investigators and student trainees (trainees) in disparities reduction. This
      paper describes the academic, mentoring, training, and work-life balance
      experiences of CNPC-affiliated trainees. METHODS: We used a collaborative and
      iterative process to develop a 57-item, web-based questionnaire completed by
      trainees from the 23 CNPCs between August 2012 and February 2013. Their CNPC
      mentors completed a 47-item questionnaire. Descriptive statistics were
      calculated. RESULTS: The final analytic sample included 189 of 269 individuals
      (70%) identified as active participants in CNPC research or training/mentoring.
      Mentors (n=45) were mostly non-Hispanic White (77.8%) and 48.9% were male.
      Mentors published a median of 6 (interquartile range [IQR], 3-12) first-authored
      and 15 (IQR, 6-25) senior authored manuscripts, and secured 15 (IQR, 11-29)
      grants from the National Institutes of Health (NIH) and other sources in the
      previous 5 years. Most trainees (n=144) were female (79.2%), 43.7% were
      underrepresented racial/ethnic minorities, and 36.8% were first-generation
      college graduates. Over the previous 5 years, trainees reported a median of 4
      (IQR, 1-6) publications as first author and 4 (IQR, 2-8) as co-author; 27.1%
      reported having one or more NIH R01s. Trainees reported satisfaction with their
      CNPC mentor (79.1%) and confidence in demonstrating most CBPR competencies.
      CONCLUSION: The CNPC training program consists of a scientifically productive
      pool of mentors and trainees. Trainees reported rates of scholarly productivity
      comparable to other national training programs and provided insights into
      relationships with mentors, academic pressures, and professional-personal life
      balance.

PMID- 26213412
TI  - Bigger is better: honeybee colonies as distributed information-gathering systems.
AB  - In collectively foraging groups, communication about food resources can play an
      important role in the organization of the group's activity. For example, the
      honeybee dance communication system allows colonies to selectively allocate
      foragers among different floral resources according to their quality. Because
      larger groups can potentially collect more information than smaller groups, they
      might benefit more from communication because it allows them to integrate and use
      that information to coordinate forager activity. Larger groups might also benefit
      more from communication because it allows them to dominate high-value resources
      by recruiting large numbers of foragers. By manipulating both colony size and the
      ability to communicate location information in the dance, we show that larger
      colonies of honeybees benefit more from communication than do smaller colonies.
      In fact, colony size and dance communication worked together to improve foraging
      performance; the estimated net gain per foraging trip was highest in larger
      colonies with unimpaired communication. These colonies also had the earliest
      peaks in foraging activity, but not the highest ones. This suggests they may find
      and recruit to resources more quickly, but not more heavily. The benefits of
      communication we observed in larger colonies are thus likely a result of more
      effective informationgathering due to massive parallel search rather than
      increased competitive ability due to heavy recruitment.

PMID- 26213413
TI  - Combining MRI with PET for partial volume correction improves image-derived input
      functions in mice.
AB  - Accurate kinetic modelling using dynamic PET requires knowledge of the tracer
      concentration in plasma, known as the arterial input function (AIF). AIFs are
      usually determined by invasive blood sampling, but this is prohibitive in murine
      studies due to low total blood volumes. As a result of the low spatial resolution
      of PET, image-derived input functions (IDIFs) must be extracted from left
      ventricular blood pool (LVBP) ROIs of the mouse heart. This is challenging
      because of partial volume and spillover effects between the LVBP and myocardium,
      contaminating IDIFs with tissue signal. We have applied the geometric transfer
      matrix (GTM) method of partial volume correction (PVC) to 12 mice injected with
      18F-FDG affected by a Myocardial Infarction (MI), of which 6 were treated with a
      drug which reduced infarction size [1]. We utilised high resolution MRI to assist
      in segmenting mouse hearts into 5 classes: LVBP, infarcted myocardium, healthy
      myocardium, lungs/body and background. The signal contribution from these 5
      classes was convolved with the point spread function (PSF) of the Cambridge split
      magnet PET scanner and a non-linear fit was performed on the 5 measured signal
      components. The corrected IDIF was taken as the fitted LVBP component. It was
      found that the GTM PVC method could recover an IDIF with less contamination from
      spillover than an IDIF extracted from PET data alone. More realistic values of Ki
      were achieved using GTM IDIFs, which were shown to be significantly different
      (p<0.05) between the treated and untreated groups.

PMID- 26213414
TI  - Free energy of the edge of an open lipid bilayer based on the interactions of its
      constituent molecules.
AB  - Lipid-bilayers are the fundamental constituents of the walls of most living cells
      and lipid vesicles, giving them shape and compartment. The formation and growing
      of pores in a lipid bilayer have attracted considerable attention from an
      energetic point of view in recent years. Such pores permit targeted delivery of
      drugs and genes to the cell, and regulate the concentration of various molecules
      within the cell. The formation of such pores is caused by various reasons such as
      changes in cell environment, mechanical stress or thermal fluctuations.
      Understanding the energy and elastic behaviour of a lipid-bilayer edge is crucial
      for controlling the formation and growth of such pores. In the present work, the
      interactions in the molecular level are used to obtain the free energy of the
      edge of an open lipid bilayer. The resulted free-energy density includes terms
      associated with flexural and torsional energies of the edge, in addition to a
      line-tension contribution. The line tension, elastic moduli, and spontaneous
      normal and geodesic curvatures of the edge are obtained as functions of molecular
      distribution, molecular dimensions, cutoff distance, and the interaction
      strength. These parameters are further analyzed by implementing a soft-core
      interaction potential in the microphysical model. The dependence of the elastic
      free-energy of the edge to the size of the pore is reinvestigated through an
      illustrative example, and the results are found to be in agreement with the
      previous observations.

PMID- 26213415
TI  - A Newcomer's Guide to Peptide Crystallography.
AB  - Here we provide a guide for adapting the tools developed for protein X-ray
      crystallography to study the structures and supramolecular assembly of peptides.
      Peptide crystallography involves selecting a suitable peptide, crystallizing the
      peptide, collecting X-ray diffraction data, processing the diffraction data,
      determining the crystallographic phases and generating an electron density map,
      building and refining models, and depositing the crystallographic structure in
      the Protein Data Bank (PDB). Advances in technology make this process easy for a
      newcomer to adopt. This paper describes techniques for determining the X-ray
      crystallographic structures of peptides: incorporation of amino acids containing
      heavy atoms for crystallographic phase determination, commercially available kits
      to crystallize peptides, modern techniques for X-ray crystallographic data
      collection, and free user-friendly software for data processing and producing a
      crystallographic structure.

PMID- 26213416
TI  - Synthesis of 3,3,3-trifluoroethyl isocyanate, carbamate and ureas. Anticancer
      activity evaluation of N-(3,3,3-trifluoroethyl)-N'-substituted ureas.
AB  - A new method is described for producing 3,3,3-trifluoroethyl isocyanate from
      perfluoroisobutene (PFIB). Isocyanate was used for synthesis of carbamates and
      ureas. A series of trifluoroethyl-substituted ureas has been tested in the
      National Cancer Institute (NCI, Bethesda, USA) by the NCI-60 DTP Human Tumor Cell
      Line Screening Program at a single high dose (10-5 M). The moderate anticancer
      activity was shown against some types of cancer on the individual human cell
      lines for leukemia, non-small cell lung cancer and renal cancer.

PMID- 26213417
TI  - Geometric analysis characterizes molecular rigidity in generic and non-generic
      protein configurations.
AB  - Proteins operate and interact with partners by dynamically exchanging between
      functional substates of a conformational ensemble on a rugged free energy
      landscape. Understanding how these substates are linked by coordinated,
      collective motions requires exploring a high-dimensional space, which remains a
      tremendous challenge. While molecular dynamics simulations can provide atomically
      detailed insight into the dynamics, computational demands to adequately sample
      conformational ensembles of large biomolecules and their complexes often require
      tremendous resources. Kinematic models can provide high-level insights into
      conformational ensembles and molecular rigidity beyond the reach of molecular
      dynamics by reducing the dimensionality of the search space. Here, we model a
      protein as a kinematic linkage and present a new geometric method to characterize
      molecular rigidity from the constraint manifold Q and its tangent space Q at the
      current configuration q. In contrast to methods based on combinatorial constraint
      counting, our method is valid for both generic and non-generic, e.g., singular
      configurations. Importantly, our geometric approach provides an explicit basis
      for collective motions along floppy modes, resulting in an efficient procedure to
      probe conformational space. An atomically detailed structural characterization of
      coordinated, collective motions would allow us to engineer or allosterically
      modulate biomolecules by selectively stabilizing conformations that enhance or
      inhibit function with broad implications for human health.

PMID- 26213418
TI  - Perceptual discrimination across contexts and contrasts in preschool-aged
      children.
AB  - This paper investigates a proposed phonetically-based account of developmental
      phonological patterns that lack counterparts in adult typology. Adult listeners
      perceive some phonemic contrasts more accurately than others, and these
      differences in perceptual recoverability are posited to represent one influence
      on phonological typology. One hypothesis suggests that children and adults could
      differ in their patterns of relative perceptual sensitivity, and these
      differences could form the basis for some child-specific phonological patterns in
      production. However, there has been a lack of empirical evidence to support this
      claim. This study used a nonword discrimination task to investigate differences
      in perceptual recoverability across contrasts and contexts in typically
      developing preschool children. Participants heard nonwords that were identical or
      differed by a single segment in initial or final position. Results revealed
      general agreement between child and adult listeners in the relative
      discriminability of different featural contrasts. For certain contrasts,
      discrimination accuracy was significantly greater in initial than final position,
      mirroring an asymmetry seen in adults. Overall, these results suggest that
      perceptual discrimination in preschool-aged children is broadly congruent with
      patterns of relative sensitivity observed in adult listeners. These findings
      suggest that factors other than perceptual recoverability should be explored to
      account for child-specific phonological patterns.

PMID- 26213419
TI  - The effect of impedance to root growth on plant architecture in wheat.
AB  - BACKGROUND AND AIMS: We were interested in the effect of impedance to root growth
      on root and shoot architecture of wheat. It is known that Rht-1 semi-dwarfing
      alleles decrease the degree of leaf stunting due to root impedance. We compared
      commercial wheat cultivars containing different Rht-1 alleles to determine
      whether leaf stunting caused by root impedance differed between cultivars. We
      investigated effects of impedance to root growth on the angular spread of roots.
      METHODS: The wheat cultivars Avalon, Robigus and Battalion, carrying semi
      dwarfing alleles of Rht-1, and cv. Cadenza, carrying the tall, wild-type allele,
      were grown under two levels of soil strength in a sand culture system designed to
      allow the mechanical impedance of the root growth environment to be adjusted
      independently of water and nutrient availability. RESULTS: Impeded roots grew
      more steeply than non-impeded roots: the angular spread of roots decreased from
      55 degrees  to 43 degrees  from the vertical, but the genotypic effects were
      weak. Root impedance reduced leaf elongation and the number of tillers. Leaf area
      and total root length provided a common relationship across all genotype x
      treatment combinations. Leaf stunting in Cadenza was more severe. CONCLUSION: Our
      data support the hypothesis that the severity of leaf stunting due to root
      impedance is related to the Rht allele. Impeded roots had a smaller angular
      spread.

PMID- 26213420
TI  - Disparities in Disability Life Expectancy in US Birth Cohorts: The Influence of
      Sex and Race.
AB  - Racial and sex disparities in chronic diseases and mortality are sources of
      health inequality and have been observed from infancy to adulthood. Disparities
      in health and mortality contribute to corresponding disparities in healthy life.
      I address two previously unanswered questions in the aging literature. First,
      does the racial and sex gap in healthy life narrow, persist, or expand over age
      and time, particularly considering severity of ill health, among the oldest old?
      Second, do some race-sex groups of birth cohorts live not just longer lives, but
      longer healthier lives, while others spend additional years in illness? To
      estimate the quantities, I employ a refined definition of physical disability and
      apply a new extension of Sullivan's method to true birth cohorts. The results
      suggest among the oldest old, few racial or sex disparities exist over age and
      time in mild disability. Yet, racial and sex disparities persist over age and
      time in severe disability.

PMID- 26213421
TI  - When Do States Respond to Low Fertility? Contexts of State Concern in Wealthier
      Countries, 1976-2011.
AB  - Since the 1970s, expressions of state concern over low fertility have greatly
      increased among wealthier countries. This study asks to what extent this increase
      is explained by demographic factors, national-level economic and political
      factors, and processes of international diffusion and changing international
      norms. Analyses integrate the world polity literature on global policy diffusion
      with a social problems approach to examine international diffusion of state
      concern among more powerful members of the world polity, a process that can
      produce changes in international policy consensus. Comparisons of the
      characteristics of states that do and do not express concern over low fertility
      find that among wealthier "first-world" countries, state concern has become more
      responsive to fertility rates: fertility rates are not significantly associated
      with concern early in the study period, but are strongly associated with concern
      later in the study period. There is no evidence that integration into the world
      polity is associated with concern in these countries, and some evidence that less
      integrated countries are more likely to express concern, suggesting that
      processes shaping the diffusion of state concern may differ from those identified
      as shaping policy diffusion in the existing literature. Among "second-world"
      former Eastern bloc countries, different patterns of associations reflect
      different political histories: concern is associated only with demographic
      factors, with no significant change in this association over time.

PMID- 26213422
TI  - How can Databases assist with the Prediction of Chemical Compounds?
AB  - An overview is given on the ways databases can be employed to aid in the
      prediction of chemical compounds, in particular inorganic crystalline compounds.
      Methods currently employed and possible future approaches are discussed.

PMID- 26213423
TI  - Ionic Liquid assisted Synthesis of Zeolite-TON.
AB  - An ionic liquid assisted strategy for the synthesis of zeolitic material is
      reported. This strategy is a solid state synthetic method and the ionic liquid is
      employed as structure directing agent. A TON-type zeolite, which contains one
      dimensional 10-member-ring, is successfully synthesized with the assistance of
      the ionic liquid, 1-ethyl-3-methylimidazolium bromide. This finding improves our
      understanding about the challenge of ionothermally synthesizing siliceous and
      aluminosilicate zeolites.

PMID- 26213424
TI  - Molybdenum L-Edge XAS Spectra of MoFe Nitrogenase.
AB  - A molybdenum L-edge X-ray absorption spectroscopy (XAS) study is presented for
      native and oxidized MoFe protein of nitrogenase as well as Mo-Fe model compounds.
      Recently collected data on MoFe protein (in oxidized and reduced forms) is
      compared to previously published Mo XAS data on the isolated FeMo cofactor in NMF
      solution and put in context of the recent Mo K-edge XAS study, which showed a
      MoIII assignment for the molybdenum atom in FeMoco. The L3-edge data are
      interpreted within a simple ligand-field model, from which a time-dependent
      density functional theory (TDDFT) approach is proposed as a way to provide
      further insights into the analysis of the molybdenum L3-edges. The calculated
      results reproduce well the relative spectral trends that are observed
      experimentally. Ultimately, these results give further support for the MoIII
      assignment in protein-bound FeMoco, as well as isolated FeMoco.

PMID- 26213425
TI  - High Voltage Electrochemiluminescence (ECL) as a New Method for Detection of PAH
      During Screening for PAH-Degrading Microbial Consortia.
AB  - The search for new bacterial consortia capable of removing PAH from the
      environment is associated with the need to employ novel, simple, and economically
      efficient detection methods. A fluorimetric method (FL) as well as high voltage
      electrochemiluminescence (ECL) on a modified surface of an aluminum electrode
      were used in order to determine the changes in the concentrations of PAH in the
      studied aqueous solutions. The ECL signal (the spectrum and emission intensity
      for a given wavelength) was determined with the use of an apparatus operating in
      single photon counting mode. The dependency of ECL and FL intensity on the
      concentration of naphthalene, phenanthrene, and pyrene was linear in the studied
      concentration range. The biodegradation kinetics of the particular PAH compounds
      was determined on the basis of the obtained spectroscopic determinations. It has
      been established that the half-life of naphthalene, phenanthrene, and pyrene at
      initial concentrations of 50 mg/l (beyond the solubility limit) reached 41, 75,
      and 130 h, accordingly. Additionally, the possibility of using ECL for rapid
      determination of the soluble fraction of PAH directly in the aqueous medium has
      been confirmed. Metagenomic analysis of the gene encoding 16S rRNA was conducted
      on the basis of V4 hypervariable region of the 16S rRNA gene and allowed to
      identify 198 species of bacteria that create the S4consortium. The consortium was
      dominated by Gammaproteobacteria (78.82 %), Flavobacteria (9.25 %),
      Betaproteobacteria (7.68 %), Sphingobacteria (3.76 %), Alphaproteobacteria (0.42
      %), Clostridia (0.04 %), and Bacilli (0.03 %).

PMID- 26213426
TI  - The basal Lutetian Transgression on the Tethyan shelf of the European craton
      (Adelholzen beds, Eastern Alps, Germany).
AB  - The middle Eocene Adelholzen beds were deposited on the northern part of the
      Tethyan shelf of the European Plate. In the Eastern Alps, the Wimmern section
      near Teisendorf (Germany) is the only known outcrop exposing the basal
      unconformity of this sequence. The outcrop comprises an 8 m thick condensed
      transgressive shallow marine succession characterized by glauconite-rich weakly
      consolidated greensand and mudstone containing abundant larger benthic
      foraminifera. It spans the lower part of calcareous nannoplankton Zone NP15 (Sub
      Zones NP15a and lower part of NP15b), planktonic foraminifera Sub-Zone E7b and
      Zone E8 partim and the upper part of shallow benthic Zone SBZ13. The landward
      migration of the paleo-shoreline was not an effect of flexural downbending of the
      European Plate but can be correlated to the major unconformity at the base of
      eustatic supercycle TA3. The onset of this sea-level rise was in the latest part
      of Biochron NP14b and almost coincided with the NP14b/NP15a-boundary.

PMID- 26213427
TI  - Changing Patterns of the Floating Population in China during 2000-2010.
AB  - Using data from the 2000 and 2010 Chinese Population Censuses and applying a
      consistent definition of migration, this paper examines changing patterns of
      China's floating population during 2000-2010. We find that during the first
      decade of the 21st century, there have been significant changes in China's
      floating population, as reflected in continuing rise of interprovincial floating
      population and the rise of the floating population in China's western and
      interior regions, geographic diversification of destinations for the floating
      population, a major increase in interprovincial return migration, and significant
      improvement in education and occupational profiles among the floating population.
      We argue that these patterns are driven by a combination of complex domestic and
      international factors, including the newly released Labor Law, removal of
      agricultural tax, the western China development program, increased investment in
      education by the Chinese government, and the global financial crisis. We also
      discuss several challenges facing the floating population in the coming years,
      which include equality of educational opportunity for migrant children and
      adequate housing and social welfare protection for the floating population.
      Finally, we reflect on the future of migration research in China.

PMID- 26213428
TI  - The moderating role of specific self-efficacy in the impact of positive mood on
      cognitive performance.
AB  - Research concerning the impact of positive mood on cognitive performance is
      inconsistent. We suggest that specific self-efficacy moderates this relationship.
      The current study proposed that participants in a positive mood with a high level
      of specific self-efficacy would anticipate mood-maintaining success on a task.
      Hence, they would be more strongly motivated, and perform better on the task,
      than individuals in other moods. Conversely, participants in a positive mood with
      low specific self-efficacy should expect mood-threatening failure. Thus, these
      individuals should be less motivated and perform more poorly than individuals in
      other moods. The current study included 139 participants with different levels of
      specific self-efficacy performing a comprehension task in either a positive or
      negative mood or a control condition. Results confirmed our hypothesis whereby
      specific self-efficacy affects cognitive performance but only during a positive
      mood. These findings support the role of specific self-efficacy in maintaining
      positive mood by regulating task activity.

PMID- 26213429
TI  - Individual differences in response to uncertainty and decision making: The role
      of behavioral inhibition system and need for closure.
AB  - In two studies, we examined the influence of behavioral inhibition system (BIS)
      and need for closure (NFC) on information processing in decision making. We
      expected that BIS would regulate behavior in a decisional context and that this
      relationship would be mediated by epistemic motivation expressed by NFC. In
      addition, drawing on contradictory findings in the literature on anxiety, NFC,
      and information processing, we investigated the moderating role of decision
      rules. The results supported our predictions. BIS was strongly and positively
      related to NFC, and through NFC it was related to decision-making style.
      Moreover, decision task characteristics moderated the relationship between NFC
      and decision making. When a task did not offer a confident decision rule, high
      NFC participants prolonged the information search more than low NFC individuals.
      However, when a reliable strategy was suggested, high NFC participants behaved in
      line with it. These results are discussed within an uncertainty management
      framework.

PMID- 26213430
TI  - Maternal Behavior and Physiological Stress Levels in Wild Chimpanzees (Pan
      troglodytes schweinfurthii).
AB  - Individual differences in maternal behavior toward, and investment in, offspring
      can have lasting consequences, particularly among primate taxa characterized by
      prolonged periods of development over which mothers can exert substantial
      influence. Given the role of the neuroendocrine system in the expression of
      behavior, researchers are increasingly interested in understanding the hormonal
      correlates of maternal behavior. Here, we examined the relationship between
      maternal behavior and physiological stress levels, as quantified by fecal
      glucocorticoid metabolite (FGM) concentrations, in lactating chimpanzees, Pan
      troglodytes schweinfurthii, at Gombe National Park, Tanzania. After accounting
      for temporal variation in FGM concentrations, we found that mothers interacted
      socially (groomed and played) with and nursed their infants more on days when FGM
      concentrations were elevated compared to days when FGM concentrations were within
      the range expected given the time of year. However, the proportion of time
      mothers and infants spent in contact did not differ based on FGM concentrations.
      These results generally agree with the suggestion that elevated GC concentrations
      are related to maternal motivation and responsivity to infant cues and are the
      first evidence of a hormonal correlate of maternal behavior in a wild great ape.

PMID- 26213432
TI  - Contribution of carbonate weathering to the CO2 efflux from temperate forest
      soils.
AB  - Temperate forests provide favorable conditions for carbonate bedrock weathering
      as the soil CO2 partial pressure is high and soil water is regularly available.
      As a result of weathering, abiotic CO2 can be released and contribute to the soil
      CO2 efflux. We used the distinct isotopic signature of the abiotic CO2 to
      estimate its contribution to the total soil CO2 efflux. Soil cores were sampled
      from forests on dolomite and limestone and were incubated under the exclusion of
      atmospheric CO2. Efflux and isotopic signatures of CO2 were repeatedly measured
      of cores containing the whole mineral soil and bedrock material (heterotrophic
      respiration + CO2 from weathering) and of cores containing only the mineral top
      soil layer (A-horizon; heterotrophic respiration). An aliquot of the cores were
      let dry out during incubation to assess effects of soil moisture. Although the
      delta13C values of the CO2 efflux from the dolomite soil cores were within a
      narrow range (A-horizon -26.2 +/- 0.1 0/00; whole soil profile wet -25.8 +/- 0.1
      0/00; whole soil profile dry -25.5 +/- 0.1 0/00) the CO2 efflux from the
      separated A-horizons was significantly depleted in 13C when compared to the whole
      soil profiles (p = 0.015). The abiotic contribution to the total CO2 efflux from
      the dolomite soil cores was 2.0 +/- 0.5 % under wet and 3.4 +/- 0.5 % under dry
      conditions. No abiotic CO2 efflux was traceable from the limestone soil cores. An
      overall low contribution of CO2 from weathering was affirmed by the amount and
      13C signature of the leached dissolved inorganic carbon (DIC) and the radiocarbon
      signature of the soil CO2 efflux in the field. Together, our data point towards
      no more than 1-2 % contribution of abiotic CO2 to the growing season soil CO2
      efflux in the field.

PMID- 26213431
TI  - Using fragmentation trees and mass spectral trees for identifying unknown
      compounds in metabolomics.
AB  - Identification of unknown metabolites is the bottleneck in advancing
      metabolomics, leaving interpretation of metabolomics results ambiguous. The
      chemical diversity of metabolism is vast, making structure identification arduous
      and time consuming. Currently, comprehensive analysis of mass spectra in
      metabolomics is limited to library matching, but tandem mass spectral libraries
      are small compared to the large number of compounds found in the biosphere,
      including xenobiotics. Resolving this bottleneck requires richer data acquisition
      and better computational tools. Multi-stage mass spectrometry (MSn) trees show
      promise to aid in this regard. Fragmentation trees explore the fragmentation
      process, generate fragmentation rules and aid in sub-structure identification,
      while mass spectral trees delineate the dependencies in multi-stage MS of
      collision-induced dissociations. This review covers advancements over the past 10
      years as a tool for metabolite identification, including algorithms, software and
      databases used to build and to implement fragmentation trees and mass spectral
      annotations.

PMID- 26213433
TI  - Comparison of first pass bolus AIFs extracted from sequential 18F-FDG PET and DSC
      MRI of mice.
AB  - Accurate kinetic modelling of in vivo physiological function using positron
      emission tomography (PET) requires determination of the tracer time-activity
      curve in plasma, known as the arterial input function (AIF). The AIF is usually
      determined by invasive blood sampling methods, which are prohibitive in murine
      studies due to low total blood volumes. Extracting AIFs from PET images is also
      challenging due to large partial volume effects (PVE). We hypothesise that in
      combined PET with magnetic resonance imaging (PET/MR), a co-injected bolus of MR
      contrast agent and PET ligand can be tracked using fast MR acquisitions. This
      protocol would allow extraction of a MR AIF from MR contrast agent concentration
      time curves, at higher spatial and temporal resolution than an image-derived PET
      AIF. A conversion factor could then be applied to the MR AIF for use in PET
      kinetic analysis. This work has compared AIFs obtained from sequential DSC-MRI
      and PET with separate injections of gadolinium contrast agent and 18F-FDG
      respectively to ascertain the technique's validity. An automated voxel selection
      algorithm was employed to improve MR AIF reproducibility. We found that MR and
      PET AIFs displayed similar character in the first pass, confirmed by gamma
      variate fits (p<0.02). MR AIFs displayed reduced PVE compared to PET AIFs,
      indicating their potential use in PET/MR studies.

PMID- 26213434
TI  - Hypervigilance to Rejecting Stimuli in Rejection Sensitive Individuals:
      Behavioral and Neurocognitive Evidence.
AB  - Individuals who are high in rejection sensitivity are vigilant toward social cues
      that signal rejection, and they exhibit attention biases towards information that
      confirms expectations of rejection. Little is known, however, about the neural
      correlates of rejection sensitivity. The present study examined whether rejection
      sensitivity is associated with individuals' neural responses to rejection
      relevant information. Female participants, classified as high or average in
      rejection sensitivity, completed a modified dot-probe task in which a neutral
      face was paired with either another neutral face or a gaze-averted ("rejecting")
      face while EEG was collected and ERP components were computed. Behavioral results
      indicated that average rejection sensitive participants showed an attention bias
      away from rejecting faces, while high rejection sensitive participants were
      equally vigilant to neutral and rejecting faces. High rejection sensitivity was
      associated with ERP components signaling elevated attention and arousal to faces.
      These findings suggest that rejection sensitivity shapes behavioral and
      neurocognitive responses to faces.

PMID- 26213435
TI  - Daily interpersonal coping strategies: Implications for self-reported well-being
      and cortisol.
AB  - An important pathway by which relationships influence health may involve how
      people cope with interpersonal tensions. This study examined whether same day and
      prior day avoidance and engagement in arguments are differentially associated
      with self-reported well-being (emotional, physical) and diurnal cortisol
      patterns. Participants from Wave 2 of the National Study of Daily Experiences
      (NSDE; N =1512; ages 33-84, 57% women), completed daily phone interviews for
      eight consecutive days and provided useable saliva samples that were assayed for
      cortisol for four of those days at specific times: waking, 30 minutes after
      waking, before lunch, and bedtime. Multilevel models revealed same day arguments
      were associated with lower well-being (higher negative affect, lower positive
      affect) than same day avoidance or no tension. In contrast, previous day
      avoidance was associated with lower next day well-being (higher negative affect,
      more physical symptoms) and higher next day cortisol than having no interpersonal
      tension the previous day. Arguments have greater same day consequences for well
      being, whereas avoided arguments have greater next day consequences, which may
      indicate delayed effects of avoidance.

PMID- 26213436
TI  - Development of Condom-Use Self-Efficacy over 36 months among Early Adolescents: A
      Mediation Analysis.
AB  - This research evaluates condom-use self-efficacy and its increase throughout
      adolescence. Documentation of the development of condom-use self-efficacy would
      be important for prevention efforts given the influence of self-efficacy on
      actual condom-usage. This study assesses a hypothesized mediation mechanism of
      the development of self-efficacy using a mediation analysis approach. The
      participants, 497 grade-6 Bahamian students, were randomly assigned to the
      control condition in a 3-year longitudinal HIV prevention program trial. Condom
      use self-efficacy consistently increased and condom-use self-efficacy assessed at
      earlier periods was positively associated with its values at subsequent periods.
      Additionally, self-efficacy assessed between two time points one year apart or
      longer (e.g., 6 months between baseline and 12 months) significantly mediated the
      impact of its levels at the previous assessment on the level at the subsequent
      assessment. To sustain program effect, HIV prevention programs should strive to
      enhance self-efficacy and provide reinforcing "boosters" no later than 12 months
      post-intervention.

PMID- 26213437
TI  - Nutritional Status of Maasai Pastoralists under Change.
AB  - This study assesses the nutritional status of Maasai pastoralists living in a
      period of great social, economic and ecological changes in Kajiado County,
      southern Kenya. Data on weight, height, skinfolds, and circumferences were
      collected from 534 individuals in the year 2000. The data were used to describe
      mean differences in human nutrition between ages, sexes, and within and among
      three Group Ranches. Nutritional data and diet recall data were compared with
      past studies of Maasai nutrition from 1930 to 2000. Results indicate that
      nutritional status is poor and has remained so despite numerous changes to the
      social-ecological system including livelihood diversification, sedentarization,
      human population growth and decreased access to vegetation heterogeneity.
      Imbirikani Group Ranch had better access to infrastructure and markets and some
      measures of nutritional status were better than for individuals in other group
      ranches. However, nutritional status remains poor despite transitioning to
      greater market integration.

PMID- 26213438
TI  - Ashaninka Palm Management and Domestication in the Peruvian Amazon.
AB  - Palms are a natural resource that has been abundantly used by Amerindians for
      centuries. Only a few palm domestications have been reported in the American
      tropics, where there is great diversity of the Arecaceae family. We report the
      results of a survey combining ethnobotanical and ecological methods to study the
      past and present management and distribution of palms by the Ashaninka indigenous
      people from the Tambo river region in the Peruvian Amazon. Our objectives were to
      document palm-related traditional ecological knowledge, to examine correlation
      between palm abundance and Ashaninka management practices and social exchange of
      palm resources, and to address the question of how the Ashaninka have modified
      palm diversity and distribution in their territory. We found that most palm
      species have multiple uses; the most intensively managed were palms that provide
      thatch, notably Attalea phalerata, Oenocarpus mapora and Phytelephas macrocarpa.
      Of these, Attalea phalerata was the most commonly cultivated and was found only
      in cultivated stands. Our results have implications for understanding the
      domestication of Attalea weberbaueri, which is a landrace within the Attalea
      phalerata complex. A closer understanding of this process would require
      morphometric and genetic methods to compare wild and managed populations.

PMID- 26213439
TI  - How habitat affects the benefits of communication in collectively foraging honey
      bees.
AB  - Honey bees (Apis mellifera) use the dance language to symbolically convey
      information about the location of floral resources from within the nest. To
      figure out why this unique ability evolved, we need to understand the benefits it
      offers to the colony. Previous studies have shown that, in fact, the location
      information in the dance is not always beneficial. We ask, in which ecological
      habitats do honey bee colonies actually benefit from the dance language, and what
      is it about those habitats that makes communication useful? In this study, we
      examine the effects of floral distribution patterns on the benefits of dance
      communication across five different habitats. In each habitat, we manipulated
      colonies' ability to communicate and measured their foraging success, while
      simultaneously characterizing the naturally occurring floral distribution. We
      find that communication is most beneficial when floral species richness is high
      and patches contain many flowers. These are ecological features that could have
      helped shape the evolution of the honey bee dance language.

PMID- 26213440
TI  - Lattice strain across Na-K interdiffusion fronts in alkali feldspar: an electron
      back-scatter diffraction study.
AB  - Cation exchange experiments between gem quality sanidine [Formula: see text] and
      KCl melt produced chemical alteration of alkali feldspar starting at the grain
      surface and propagating inwards by highly anisotropic Na-K interdiffusion on the
      alkali sublattice. Diffusion fronts developing in b-direction are very sharp,
      while diffusion fronts within the a-c-plane are comparatively broad. Due to the
      composition dependence of the lattice parameters of alkali feldspar, the
      diffusion induced compositional heterogeneity induces coherency stress and
      elastic strain. Electron back-scatter diffraction combined with the cross
      correlation technique was employed to determine the lattice strain distribution
      across the Na-K interdiffusion fronts in partially exchanged single crystals of
      alkali feldspar. The strain changes gradually across the broad fronts within the
      a-c-plane, with a successive extension primarily in a-direction conferring to the
      composition strain in unstressed alkali feldspar. In contrast, lattice strain
      characterised by pronounced extension in b-direction is localised at the sharp
      diffusion fronts parallel to b, followed by a slight expansion in a-direction in
      the orthoclase-rich rim. This strain pattern does not confer with the composition
      induced lattice strain in a stress-free alkali feldspar. It may rather be
      explained by the mechanical coupling of the exchanged surface layer and the
      mechanically strong substratum. The lattice distortion localised at the sharp
      diffusion front may have an influence on the diffusion process and appears to
      produce a self-sharpening feedback, leading to a local reduction of component
      mobilities.

PMID- 26213441
TI  - First-principles investigation of the lattice vibrations in the alkali feldspar
      solid solution.
AB  - The heat capacities of Al, Si ordered alkali feldspars of different Na, K
      compositions were calculated using the density functional theory. The effect of
      the Na, K distribution, if random, ordered or clustered, on the resulting heat
      capacity was investigated on different cells with Ab50Or50 composition. For all
      compositions and distributions studied, the excess heat capacity of mixing is
      positive at low temperatures with a maximum at ~60 K. This produces an increasing
      excess vibrational entropy that reaches a constant value above ~200 K. The amount
      of the excess heat capacity of Ab50Or50, however, depends on the Na, K
      distribution. Best agreement with measured excess heat capacities is achieved, if
      the distribution of Na and K is either ordered or clustered. The positive excess
      heat capacities can be attributed to a strong softening of the acoustic and the
      lowest optical modes related to a strong increase of Na-O bond lengths in samples
      with intermediate compositions. The softening of the lowest optical mode is,
      however, not reflected by thoroughly measured literature IR data. Comparing
      calculated and measured IR spectra suggests that the resolution of the measured
      spectra was insufficient for detecting the lowest IR-active modes.

PMID- 26213442
TI  - Neutral Caregivers or Military Support? The British Red Cross, the Friends'
      Ambulance Unit, and the Problems of Voluntary Medical Aid in Wartime.
AB  - During the First World War the British Red Cross Society (BRCS) served as the
      coordinating body for voluntary medical aid giving in Britain. Among the many
      units which came within its purview was the Friends' Ambulance Unit (FAU), formed
      by a group of young men whose desire to serve their nation in wartime conflicted
      with their pacifist principles. Both the BRCS and the FAU were wracked by
      ideological conflicts in the years which preceded and throughout the war. These
      struggles over voluntarist identity highlight the contested meanings of service
      and conscience in wartime. Through a critical examination of the language of
      official histories and biographies, this article will argue that the war formed a
      key moment in the relationship between the British state and voluntary medical
      aid, with the state's increasing role in the work of such organizations raising
      questions about the voluntarist principles to which aid organizations laid claim.
      The struggles that both organizations and individuals within them faced in
      reconciling the competing pressures that this new relationship created form a
      legacy of the war which continues to have important implications for the place of
      medical voluntarism in wartime today.

PMID- 26213443
TI  - All Together Now: Measuring Staff Cohesion in Special Education Classrooms.
AB  - This study sought to validate a new measure, the Classroom Cohesion Survey (CCS),
      designed to examine the relationship between teachers and classroom assistants in
      autism support classrooms. Teachers, classroom assistants, and external observers
      showed good inter-rater agreement on the CCS and good internal consistency for
      all scales. Simple factor structures were found for both teacher- and classroom
      assistant-rated scales, with one-factor solutions for both scales. Paired t tests
      revealed that on average, classroom assistants rated classroom cohesion stronger
      than teachers. The CCS may be an effective tool for measuring cohesion between
      classroom staff and may have an important impact on various clinical and
      implementation outcomes in school settings.

PMID- 26213444
TI  - Psychometric Validation of the Self-Efficacy for Restricting Dietary Salt in
      Hemodialysis Scale.
AB  - The development and progression of left ventricular hypertrophy is a consequence
      of multiple comorbid conditions associated with end-stage renal disease and large
      variations in interdialytic weight gains. The literature suggests that dietary
      sodium restriction alone significantly reduces interdialytic weight gains. A
      total of 124 hemodialysis participants in an ongoing randomized control trial
      participated in the validation in which psychometric properties of a self
      efficacy survey were a secondary analysis. We evaluated the internal consistency,
      construct validity, and convergent validity of the instrument. The overall
      Cronbach alpha was 0.93. Three factors extracted explain 67.8% of the variance of
      the white and African American participants. The Self-Efficacy Survey has
      adequate internal consistency and construct and convergent validity. Future
      research is needed to evaluate the stability and discriminant validity of the
      instrument.

PMID- 26213445
TI  - Clinical Implications of Temperamental Characteristics in Young Children with
      Developmental Disabilities.
AB  - Temperament refers to the behavioral style of an individual, or the tendency to
      behave in a certain way in a certain situation. Although temperament has been
      studied extensively in typically developing children, relatively little research
      concerning individual differences in the behavioral styles of young children with
      developmental disabilities has been conducted. The purposes of this article are:
      (1) to provide a brief review of the literature with regard to temperament and
      outcomes for children with developmental disabilities and, (2) to explore methods
      for integrating temperament information into early intervention practice.
      Consistent with the research on temperament and goodness of fit (Chess & Thomas,
      1996), this article proposes that children with developmental disabilities who
      present with extreme scores in specific domains of temperament may benefit from
      specific early intervention practices. Ideas for linking practice with child
      temperament are presented, particularly for children who are resistant to change,
      non-persistent, or difficult to distract.

PMID- 26213446
TI  - International Human Rights to Early Intervention for Infants and Young Children
      with Disabilities: Tools for Global Advocacy.
AB  - With almost universal ratification of the Convention on the Rights of the Child
      and the growing number of States Parties that have signed or ratified the
      Convention on the Rights of Persons with Disabilities, the majority of countries
      in the world have now committed to implementing the human rights articulated in
      these treaties. In this article we first provide an overview of both Conventions,
      highlight the articles in the treaties that are relevant to early intervention
      for infants and young children with disabilities, and describe the specific
      duties required of States Parties to ensure compliance including international
      cooperation. Second, a series of early intervention action principles are put
      forward that can help States Parties translate the underlying values of the
      Conventions into practice.

PMID- 26213447
TI  - Developmental Science and Preventive Interventions for Children at Environmental
      Risk.
AB  - The current status of preventive intervention programs for young children at
      environmental risk designed to reduce the school readiness gap is examined in the
      context of developmental science. A review of program effectiveness suggests that
      future progress may depend upon committing to a specific developmental approach
      consistent with the knowledge base of developmental science and establishing a
      generally agreed upon and unambiguous framework, set of goals, and associated
      mechanisms. The Developmental Systems Approach is suggested as one model that is
      consistent with developmental and existing intervention science, supporting an
      emphasis on program continuity, relationships, and comprehensiveness. A long-term
      plan for community-based systems development is presented.

PMID- 26213448
TI  - Development of a cobinamide-based end-of-service-life indicator for detection of
      hydrogen cyanide gas.
AB  - We describe an inexpensive paper-based sensor for rapid detection of low
      concentrations (ppm) of hydrogen cyanide gas. A piece of filter paper pre-spotted
      with a dilute monocyanocobinamide [CN(H2O)Cbi] solution was placed on the end of
      a bifurcated optical fiber and the reflectance spectrum of the CN(H2O)Cbi was
      monitored during exposure to 1.0-10.0 ppm hydrogen cyanide gas. Formation of
      dicyanocobinamide yielded a peak at 583 nm with a simultaneous decrease in
      reflectance from 450-500 nm. Spectral changes were monitored as a function of
      time at several relative humidity values: 25, 50, and 85% relative humidity. With
      either cellulose or glass fiber papers, spectral changes occurred within 10 s of
      exposure to 5.0 ppm hydrogen cyanide gas (NIOSH recommended short-term exposure
      limit). We conclude that this sensor could provide a real-time end-of-service
      life alert to a respirator user.

PMID- 26213449
TI  - Facile Fabrication of Spherical Nanoparticle-Tipped AFM Probes for Plasmonic
      Applications.

PMID- 26213450
TI  - Controlling False Discovery Rate in Signal Space for Transformation-Invariant
      Thresholding of Statistical Maps.
AB  - Thresholding statistical maps with appropriate correction of multiple testing
      remains a critical and challenging problem in brain mapping. Since the false
      discovery rate (FDR) criterion was introduced to the neuroimaging community a
      decade ago, various improvements have been proposed. However, a highly desirable
      feature, transformation invariance, has not been adequately addressed, especially
      for voxel-based FDR. Thresholding applied after spatial transformation is not
      necessarily equivalent to transformation applied after thresholding in the
      original space. We find this problem closely related to another important issue:
      spatial correlation of signals. A Gaussian random vector-valued image after
      normalization is a random map from a Euclidean space to a high-dimension unit
      sphere. Instead of defining the FDR measure in the image's Euclidean space, we
      define it in the signals' hyper-spherical space whose measure not only reflects
      the intrinsic "volume" of signals' randomness but also keeps invariant under
      images' spatial transformation. Experiments with synthetic and real images
      demonstrate that our method achieves transformation invariance and significantly
      minimizes the bias introduced by the choice of template images.

PMID- 26213451
TI  - Simultaneous Longitudinal Registration with Group-Wise Similarity Prior.
AB  - Here we present an algorithm for the simultaneous registration of N longitudinal
      image pairs such that information acquired by each pair is used to constrain the
      registration of each other pair. More specifically, in the geodesic shooting
      setting for Large Deformation Diffeomorphic Metric Mappings (LDDMM) an average of
      the initial momenta characterizing the N transformations is maintained throughout
      and updates to individual momenta are constrained to be similar to this average.
      In this way, the N registrations are coupled and explore the space of
      diffeomorphisms as a group, the variance of which is constrained to be small. Our
      approach is motivated by the observation that transformations learned from images
      in the same diagnostic category share characteristics. The group-wise consistency
      prior serves to strengthen the contribution of the common signal among the N
      image pairs to the transformation for a specific pair, relative to features
      particular to that pair. We tested the algorithm on 57 longitudinal image pairs
      of Alzheimer's Disease patients from the Alzheimer's Disease Neuroimaging
      Initiative and evaluated the ability of the algorithm to produce momenta that
      better represent the long-term biological processes occurring in the underlying
      anatomy. We found that for many image pairs, momenta learned with the group-wise
      prior better predict a third time point image unobserved in the registration.

PMID- 26213452
TI  - Spatially Weighted Principal Component Regression for High-Dimensional
      Prediction.
AB  - We consider the problem of using high dimensional data residing on graphs to
      predict a low-dimensional outcome variable, such as disease status. Examples of
      data include time series and genetic data measured on linear graphs and imaging
      data measured on triangulated graphs (or lattices), among many others. Many of
      these data have two key features including spatial smoothness and intrinsically
      low dimensional structure. We propose a simple solution based on a general
      statistical framework, called spatially weighted principal component regression
      (SWPCR). In SWPCR, we introduce two sets of weights including importance score
      weights for the selection of individual features at each node and spatial weights
      for the incorporation of the neighboring pattern on the graph. We integrate the
      importance score weights with the spatial weights in order to recover the low
      dimensional structure of high dimensional data. We demonstrate the utility of our
      methods through extensive simulations and a real data analysis based on
      Alzheimer's disease neuroimaging initiative data.

PMID- 26213453
TI  - Functional Nonlinear Mixed Effects Models for Longitudinal Image Data.
AB  - Motivated by studying large-scale longitudinal image data, we propose a novel
      functional nonlinear mixed effects modeling (FNMEM) framework to model the
      nonlinear spatial-temporal growth patterns of brain structure and function and
      their association with covariates of interest (e.g., time or diagnostic status).
      Our FNMEM explicitly quantifies a random nonlinear association map of individual
      trajectories. We develop an efficient estimation method to estimate the nonlinear
      growth function and the covariance operator of the spatial-temporal process. We
      propose a global test and a simultaneous confidence band for some specific growth
      patterns. We conduct Monte Carlo simulation to examine the finite-sample
      performance of the proposed procedures. We apply FNMEM to investigate the spatial
      temporal dynamics of white-matter fiber skeletons in a national database for
      autism research. Our FNMEM may provide a valuable tool for charting the
      developmental trajectories of various neuropsychiatric and neurodegenerative
      disorders.

PMID- 26213454
TI  - Cultural Adaptation of Interventions in Real Practice Settings.
AB  - This article provides an overview of some common challenges and opportunities
      related to cultural adaptation of behavioral interventions. Cultural adaptation
      is presented as a necessary action to ponder when considering the adoption of an
      evidence-based intervention with ethnic and other minority groups. It proposes a
      roadmap to choose existing interventions and a specific approach to evaluate
      prevention and treatment interventions for cultural relevancy. An approach to
      conducting cultural adaptations is proposed, followed by an outline of a cultural
      adaptation protocol. A case study is presented, and lessons learned are shared as
      well as recommendations for culturally grounded social work practice.

PMID- 26213455
TI  - Untangling Psychiatric Comorbidity in Young Children Who Experienced Single,
      Repeated, or Hurricane Katrina Traumatic Events.
AB  - BACKGROUND: In individuals with posttraumatic stress disorder (PTSD), 70%-90%
      have at least one comorbid non-PTSD disorder. OBJECTIVE: This study tested
      several hypotheses to untangle comorbidity issues. Following McMillen et al.
      (2002), we hypothesized that few non-PTSD disorders would arise following
      traumatic events in children with substantial PTSD symptoms. Second, Repeated
      Events victims would show more internalizing and externalizing problems compared
      to Single Event and Hurricane Katrina victims. Third, we aimed to replicate in
      young children the finding from older populations that exposure to multiple
      events, not the type of event, would predict severity of symptoms. These results
      would inform speculations that repeated and prolonged traumas produce greater
      symptom complexity. METHODS: Children 3-6 years of age were recruited for three
      types of trauma: Single (n=62), Hurricane Katrina (n=85), and Repeated Events
      (n=137), and assessed with caregiver reports from a diagnostic interview.
      RESULTS: Overall, 95% of children who developed new non-PTSD disorders following
      traumas also had substantial PTSD symptoms. The Katrina and Repeated Events
      groups showed more diagnoses of oppositional defiant disorder compared to the
      Single Event group, but groups did not differ on PTSD, depression, anxiety, or
      attention-deficit/hyperactivity disorder. Cumulative number of events was the
      only significant predictor of PTSD symptoms, while type of trauma and total
      occurrences of traumas did not predict additional variance. CONCLUSION: These
      data provide empirical support for targeting interventions on PTSD following
      traumas and disasters. The homogeneity of outcomes across types of traumas
      provides little empirical support for speculations that repeated and prolonged
      traumas produce greater symptom complexity.

PMID- 26213456
TI  - Synthesis and antibacterial activity of Schiff bases and amines derived from
      alkyl 2-(2-formyl-4-nitrophenoxy)alkanoates.
AB  - A series of novel Schiff bases and secondary amines were obtained in good yields,
      as a result of the reductive amination of alkyl 2-(2-formyl-4
      nitrophenoxy)alkanoates with both aniline and 4-methoxyaniline under established
      mild reaction conditions. Sodium triacetoxyborohydride as well as hydrogen in the
      presence of palladium on carbon were used as efficient reducing agents of the
      Schiff bases, in both direct and stepwise reductive amination processes. The
      Schiff bases, amines, and amine hydrochlorides were designed as potential
      antibacterial agents, and structure-activity relationship could be established
      following in vitro assays against Gram-positive and Gram-negative bacteria. The
      minimal inhibitory concentration and zone of inhibition were also determined. In
      these tests, some of Schiff bases and secondary amine hydrochlorides showed
      moderate-to-good activity against Gram-positive bacteria, including S. aureus, M.
      luteus, and S. mutans.

PMID- 26213457
TI  - Earth Conductivity Estimation from Through-the-Earth Measurements of 94 Coal
      Mines Using Different Electromagnetic Models.
AB  - Through-the-Earth (TTE) communication systems require minimal infrastructure to
      operate. Hence, they are assumed to be more survivable and more conventional than
      other underground mine communications systems. This survivability is a major
      advantage for TTE systems. In 2006, Congress passed the Mine Improvement and New
      Emergency Response Act (MINER Act), which requires all underground coal mines to
      install wireless communications systems. The intent behind this mandate is for
      trapped miners to be able to communicate with surface personnel after a major
      accident-hence, the interest in TTE communications. To determine the likelihood
      of establishing a TTE communication link, it would be ideal to be able to predict
      the apparent conductivity of the overburden above underground mines. In this
      paper, all 94 mine TTE measurement data collected by Bureau of Mines in the 1970s
      and early 1980s, are analyzed for the first time to determine the apparent
      conductivity of the overburden based on three different models: a homogenous half
      space model, a thin sheet model, and an attenuation factor or Q-factor model. A
      statistical formula is proposed to estimate the apparent earth conductivity for a
      specific mine based on the TTE modeling results given the mine depth and signal
      frequency.

PMID- 26213458
TI  - Incorporating Mobile Phone Technologies to Expand Evidence-Based Care.
AB  - Ownership of mobile phones is on the rise, a trend in uptake that transcends age,
      region, race, and ethnicity, as well as income. It is precisely the emerging
      ubiquity of mobile phones that has sparked enthusiasm regarding their capacity to
      increase the reach and impact of health care, including mental health care.
      Community-based clinicians charged with transporting evidence-based interventions
      beyond research and training clinics are in turn, ideally and uniquely situated
      to capitalize on mobile phone uptake and functionality to bridge the efficacy to
      effectiveness gap. As such, this article delineates key considerations to guide
      these frontline clinicians in mobile phone-enhanced clinical practice, including
      an overview of industry data on the uptake of and evolution in the functionality
      of mobile phone platforms, conceptual considerations relevant to the integration
      of mobile phones into practice, representative empirical illustrations of mobile
      phone enhanced assessment and treatment, and practical considerations relevant to
      ensuring the feasibility and sustainability of such an approach.

PMID- 26213459
TI  - The Application of a Three-Tier Model of Intervention to Parent Training.
AB  - A three-tier intervention system was designed for use with parents with preschool
      children with developmental disabilities to modify parent-child interactions. A
      single-subject changing-conditions design was used to examine the utility of a
      three-tier intervention system in reducing negative parenting strategies,
      increasing positive parenting strategies, and reducing child behavior problems in
      parent-child dyads (n = 8). The three intervention tiers consisted of (a) self
      administered reading material, (b) group training, and (c) individualized video
      feedback sessions. Parental behavior was observed to determine continuation or
      termination of intervention. Results support the utility of a tiered model of
      intervention to maximize treatment outcomes and increase efficiency by minimizing
      the need for more costly time-intensive interventions for participants who may
      not require them.

PMID- 26213461
TI  - Downregulation of miR203 induces overexpression of PIK3CA and predicts poor
      prognosis of gastric cancer patients.
AB  - BACKGROUND: Despite advances in clinical therapies and technologies, the
      prognosis for patients with gastric cancer is still poor. The aim of this study
      is to investigate new predictive markers for prognosis of gastric cancer.
      METHODS: In this study, we evaluated the expression pattern of PIK3CA in 107
      gastric cancer specimens and their adjacent nontumorous tissues. PIK3CA siRNA was
      synthesized and transfected into gastric cancer cell lines. Colony formation and
      MTT assays were employed to analyze the cell proliferation. PIK3CA expression was
      examined by using immunohistochemical analysis and Western blot assay. Transwell
      invasion assay was used to detect the invasion capability of the cells.
      Luciferase activity was examined by using 3'-untranslated region luciferase
      reporter assays. RESULTS: We observed that PIK3CA was significantly upregulated
      in gastric cancer tissues. High expression level of PIK3CA was detectable in 48
      (44.86%) of the gastric cancer specimens, and correlated with poor prognosis. In
      addition, our study indicated that miR203 inhibits cell proliferation and
      invasion via directly targeting and suppressing the PIK3CA expression. MiR203
      expression is downregulated in gastric cancer tissues. Moreover, low expression
      level of miR203 predicted poor prognosis of gastric patients and induced
      overexpression of PIK3CA. Our further study also reported that overexpression of
      miR203 inhibited phosphorylation of AKT, while cotransfection of PIK3CA reversed
      the effect of miR203. CONCLUSION: Our study suggested a miR203-PIK3CA-AKT
      signaling pathway in gastric cancer cells. This signaling pathway might play an
      important role in gastric cancer genesis and development.

PMID- 26213460
TI  - Dexamethasone intravitreal implant in the treatment of diabetic macular edema.
AB  - Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory
      reaction, and is characterized by blood-retinal barrier (BRB) breakdown and
      retinal capillary leakage. Corticosteroids are of therapeutic benefit because of
      their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery
      modes include periocular and intravitreal (via pars plana) injection. To offset
      the short intravitreal half-life of corticosteroid solutions (~3 hours) and the
      need for frequent intravitreal injections, sustained-release intravitreal
      corticosteroid implants have been developed. Dexamethasone intravitreal implant
      provides retinal drug delivery for <=6 months and recently has been approved for
      use in the treatment of DME. Pooled findings (n=1,048) from two large-scale,
      randomized Phase III trials indicated that dexamethasone intravitreal implant
      (0.35 mg and 0.7 mg) administered at >=6-month intervals produced sustained
      improvements in best-corrected visual acuity (BCVA) and macular edema.
      Significantly more patients showed a >=15-letter gain in BCVA at 3 years with
      dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection
      (18.4% and 22.2% vs 12.0%). Anatomical assessments showed rapid and sustained
      reductions in macular edema and slowing of retinopathy progression. Phase II
      study findings suggest that dexamethasone intravitreal implant is effective in
      focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with
      laser therapy. Ocular complications of dexamethasone intravitreal implant in
      Phase III trials included cataract-related events (66.0% in phakic patients),
      intraocular pressure elevation >=25 mmHg (29.7%), conjunctival hemorrhage
      (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival
      hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye
      (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous
      loss, endophthalmitis) were infrequent (<2%). Dexamethasone intravitreal implant
      offers a viable treatment option for DME, especially in cases that are persistent
      or treatment (anti-vascular endothelial growth factor/laser) refractory. 

PMID- 26213462
TI  - Bacteriophage-based therapy in cystic fibrosis-associated Pseudomonas aeruginosa
      infections: rationale and current status.
AB  - Pulmonary infections involving Pseudomonas aeruginosa are among the leading
      causes of the deterioration of the respiratory status of cystic fibrosis (CF)
      patients. The emergence of multidrug-resistant strains in such populations,
      favored by iterative antibiotic cures, has led to the urgent need for new
      therapies. Among them, bacteriophage-based therapies deserve a focus. One century
      of empiric use in the ex-USSR countries suggests that bacteriophages may have
      beneficial effects against a large range of bacterial infections. Interest in
      bacteriophages has recently renewed in Western countries, and the in vitro data
      available suggest that bacteriophage-based therapy may be of significant interest
      for the treatment of pulmonary infections in CF patients. Although the clinical
      data concerning this specific population are relatively scarce, the beginning of
      the first large randomized study evaluating bacteriophage-based therapy in burn
      infections suggests that the time has come to assess the effectiveness of this
      new therapy in CF P. aeruginosa pneumonia. Consequently, the aim of this review
      is, after a brief history, to summarize the evidence concerning bacteriophage
      efficacy against P. aeruginosa and, more specifically, the in vitro studies,
      animal models, and clinical trials targeting CF. 

PMID- 26213463
TI  - Treatment of Staphylococcus aureus-induced chronic osteomyelitis with bone-like
      hydroxyapatite/poly amino acid loaded with rifapentine microspheres.
AB  - PURPOSE: The purpose of this study was to investigate the curative effect of bone
      like hydroxyapatite/poly amino acid (BHA/PAA) as a carrier for poly(lactic-co
      glycolic acid)-coated rifapentine microsphere (RPM) in the treatment of rabbit
      chronic osteomyelitis induced by Staphylococcus aureus. METHODS: RPM was prepared
      through an oil-in-water emulsion solvent evaporation method, and RPM was combined
      with BHA/PAA to obtain drug-loaded, slow-releasing materials. Twenty-six New
      Zealand white rabbits were induced to establish the animal model of chronic
      osteomyelitis. After debridement, the animals were randomly divided into three
      groups (n=8): the experimental group (with RPM-loaded BHA/PAA), the control group
      (with BHA/PAA), and the blank group. The RPM-loaded BHA/PAA was evaluated for
      antibacterial activity, dynamics of drug release, and osteogenic ability through
      in vitro and in vivo experiments. RESULTS: In vitro, RPM-loaded BHA/PAA released
      the antibiotics slowly, inhibiting the bacterial growth of S. aureus for up to 5
      weeks. In vivo, at week 4, the bacterial colony count was significantly lower in
      the experimental group than in the control and blank groups (P<0.01). At week 12,
      the chronic osteomyelitis was cured and the bone defect was repaired in the
      experimental group, whereas the infection and bone defect persisted in the
      control and blank groups. CONCLUSION: In vitro and in vivo experiments
      demonstrated that RPM-loaded BHA/PAA effectively cured S. aureus-induced chronic
      osteomyelitis. Therefore, BHA/PAA has potential value as a slow-releasing
      material in clinical setting. Further investigation is needed to determine the
      optimal dosage for loading rifapentine.

PMID- 26213465
TI  - Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting
      MRI contrast agent.
AB  - A tumor-targeting carrier, hyaluronic acid (HA)-functionalized single-walled
      carbon nanotubes (SWCNTs), was explored to deliver magnetic resonance imaging
      (MRI) contrast agents (CAs) targeting to the tumor cells specifically. In this
      system, HA surface modification for SWCNTs was simply accomplished by amidation
      process and could make this nanomaterial highly hydrophilic. Cellular uptake was
      performed to evaluate the intracellular transport capabilities of HA-SWCNTs for
      tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of
      HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI
      CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand
      as a biocompatible nanocarrier and gadolinium (Gd)/HA-SWCNTs demonstrated almost
      no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could
      significantly increase the circulation time for MRI. Finally, to investigate the
      MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of
      tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the
      highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA
      SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3,
      for the identifiable diagnosis of tumor. 

PMID- 26213464
TI  - Underdiagnosis and prognosis of chronic obstructive pulmonary disease after
      percutaneous coronary intervention: a prospective study.
AB  - BACKGROUND: Retrospective studies based on clinical data and without spirometric
      confirmation suggest a poorer prognosis of patients with ischemic heart disease
      (IHD) and chronic obstructive pulmonary disease (COPD) following percutaneous
      coronary intervention (PCI). The impact of undiagnosed COPD in these patients is
      unknown. We aimed to evaluate the prognostic impact of COPD - previously or newly
      diagnosed - in patients with IHD treated with PCI. METHODS: Patients with IHD
      confirmed by PCI were consecutively included. After PCI they underwent forced
      spirometry and evaluation for cardiovascular risk factors. All-cause mortality,
      new cardiovascular events, and their combined endpoint were analyzed. RESULTS: A
      total of 133 patients (78%) male, with a mean (SD) age of 63 (10.12) years were
      included. Of these, 33 (24.8%) met the spirometric criteria for COPD, of whom
      81.8% were undiagnosed. IHD patients with COPD were older, had more coronary
      vessels affected, and a greater history of previous myocardial infarction. Median
      follow-up was 934 days (interquartile range [25%-75%]: 546-1,160). COPD patients
      had greater mortality (P=0.008; hazard ratio [HR]: 8.85; 95% confidence interval
      [CI]: 1.76-44.47) and number of cardiovascular events (P=0.024; HR: 1.87; 95% CI:
      1.04-3.33), even those without a previous diagnosis of COPD (P=0.01; HR: 1.78;
      95% CI: 1.12-2.83). These differences remained after adjustment for sex, age,
      number of coronary vessels affected, and previous myocardial infarction (P=0.025;
      HR: 1.83; 95% CI: 1.08-3.1). CONCLUSION: Prevalence and underdiagnosis of COPD in
      patients with IHD who undergo PCI are both high. These patients have an
      independent greater mortality and a higher number of cardiovascular events during
      follow-up.

PMID- 26213466
TI  - Significance of postgrowth processing of ZnO nanostructures on antibacterial
      activity against gram-positive and gram-negative bacteria.
AB  - In this work, we highlighted the effect of surface modifications of one
      dimensional (1D) ZnO nanostructures (NSs) grown by the vapor-solid mechanism on
      their antibacterial activity. Two sets of ZnO NSs were modified separately - one
      set was modified by annealing in an Ar environment, and the second set was
      modified in O2 plasma. Annealing in Ar below 800 degrees C resulted in a
      compressed lattice, which was due to removal of Zn interstitials and increased O
      vacancies. Annealing above 1,000 degrees C caused the formation of a new
      prominent phase, Zn2SiO4. Plasma oxidation of the ZnO NSs caused an expansion in
      the lattice due to the removal of O vacancies and incorporation of excess O.
      Photoluminescence (PL) spectroscopy was employed for the quantification of
      defects associated with Zn and O in the as-grown and processed ZnO NS. Two
      distinct bands were observed, one in the ultraviolet (UV) region, due to
      interband transitions, and other in the visible region, due to defects associated
      with Zn and O. PL confirmed the surface modification of ZnO NS, as substantial
      decrease in intensities of visible band was observed. Antibacterial activity of
      the modified ZnO NSs demonstrated that the surface modifications by Ar annealing
      limited the antibacterial characteristics of ZnO NS against Staphylococcus
      aureus. However, ZnO NSs annealed at 1,000 degrees C or higher showed a
      remarkable antibacterial activity against Escherichia coli. O2 plasma-treated NS
      showed appreciable antibacterial activity against both E. coli and S. aureus. The
      minimum inhibition concentration was determined to be 0.5 mg/mL and 1 mg/mL for
      Ar-annealed and plasma-oxidized ZnO NS, respectively. It was thus proved that the
      O content at the surface of the ZnO NS was crucial to tune the antibacterial
      activity against both selected gram-negative (E. coli) and gram-positive (S.
      aureus) bacterial species. 

PMID- 26213467
TI  - Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer
      nano drug delivery system.
AB  - The study investigated the reversal of multidrug resistance (MDR) and the
      biodistribution of nanoparticles (NPs) that target leukemia cells in a nude mice
      model via a surface-bound transferrin (Tf). The cytotoxic cargo of daunorubicin
      (DNR) and tetrandrine (Tet) was protected in the NPs by an outer coat composed of
      polyethylene glycol (PEG)-poly-L-lysine (PLL)-poly(lactic-co-glycolic acid)
      (PLGA) NPs. Injection of DNR-Tet-Tf-PEG-PLL-PLGA NPs into nude mice bearing MDR
      leukemia cell K562/A02 xenografts was shown to inhibit tumor growth, and
      contemporaneous immunohistochemical analysis of tumor tissue showed the targeted
      NPs induced apoptosis in tumor cells. Targeted tumor cells exhibited a marked
      increase in Tf receptor expression, with noticeable decreases in P-glycoprotein,
      MDR protein, and nuclear factor kappaB, as assessed by quantitative real-time
      polymerase chain reaction and Western blot analysis. Moreover, the concentration
      of DNR was shown to increase in plasma, tumor tissue, and major organs. Flow
      cytometry analysis with a near-infrared fluorescent (NIRF) dye, NIR797, was used
      to study the effectiveness of Tf as a targeting group for leukemia cells, a
      finding that was supported by NIRF imaging in tumor-bearing nude mice. In
      summary, our studies show that DNR-Tet-Tf-PEG-PLL-PLGA NPs provide a specific and
      effective means to target cytotoxic drugs to MDR tumor cells.

PMID- 26213468
TI  - Effects of a micro/nano rough strontium-loaded surface on osseointegration.
AB  - We developed a hierarchical hybrid micro/nanorough strontium-loaded Ti (MNT-Sr)
      surface fabricated through hydrofluoric acid etching followed by magnetron
      sputtering and evaluated the effects of this surface on osseointegration. Samples
      with a smooth Ti (ST) surface, micro Ti (MT) surface treated with hydrofluoric
      acid etching, and strontium-loaded nano Ti (NT-Sr) surface treated with SrTiO3
      target deposited via magnetron sputtering technique were investigated in parallel
      for comparison. The results showed that MNT-Sr surfaces were prepared
      successfully and with high interface bonding strength. Moreover, slow Sr release
      could be detected when the MNT-Sr and NT-Sr samples were immersed in phosphate
      buffered saline. In in vitro experiments, the MNT-Sr surface significantly
      improved the proliferation and differentiation of osteoblasts compared with the
      other three groups. Twelve weeks after the four different surface implants were
      inserted into the distal femurs of 40 rats, the bone-implant contact in the ST,
      MT, NT-Sr, and MNT-Sr groups were 39.70%+/-6.00%, 57.60%+/-7.79%, 46.10%+/-5.51%,
      and 70.38%+/-8.61%, respectively. In terms of the mineral apposition ratio, the
      MNT-Sr group increased by 129%, 58%, and 25% compared with the values of the ST,
      MT, and NT-Sr groups, respectively. Moreover, the maximal pullout force in the
      MNT-Sr group was 1.12-, 0.31-, and 0.69-fold higher than the values of the ST,
      MT, and NT-Sr groups, respectively. These results suggested that the MNT-Sr
      surface has a synergistic effect of hierarchical micro/nano-topography and
      strontium for enhanced osseointegration, and it may be a promising option for
      clinical use. Compared with the MT surface, the NT-Sr surface significantly
      improved the differentiation of osteoblasts in vitro. In the in vivo animal
      experiment, the MT surface significantly enhanced the bone-implant contact and
      maximal pullout force than the NT-Sr surface. 

PMID- 26213469
TI  - Enhanced therapeutic efficacy of budesonide in experimental colitis with
      enzyme/pH dual-sensitive polymeric nanoparticles.
AB  - Current colon-targeted drug-delivery approaches for colitis therapy often utilize
      single pH-triggered systems, which are less reliable due to the variation of gut
      pH in individuals and in disease conditions. Herein, we prepared budesonide
      loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and
      pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic
      potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat
      colitis model and compared to single pH-triggered nanoparticles. Clinical
      activity scores, colon/body weight ratios, myeloperoxidase activity, and
      proinflammatory cytokine levels were markedly decreased by dual-sensitive
      nanoparticles compared to single pH-triggered nanoparticles and budesonide
      solution. Moreover, dual-sensitive nanoparticles accumulated selectively in
      inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma
      concentrations were lower than single pH-triggered nanoparticles, and no
      noticeable in vitro or in vivo toxicity was observed. Our results demonstrate
      that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon
      targeted delivery system for colitis therapy. 

PMID- 26213470
TI  - Stress, anxiety, and depression among medical students in a multiethnic setting.
AB  - BACKGROUND: Contemporary literature suggests that medical education might
      adversely affect students' mental health. Alfaisal University in Riyadh, Saudi
      Arabia is a developing institution; hence, there has been a concern regarding the
      mental well-being of the students. OBJECTIVES: This study was designed to assess
      the traits of depression, anxiety, and stress among students in relation to
      potential underlying reasons. METHODS: All 575 medical students across the 5
      years of study participated by filling out the Depression, Anxiety, and Stress
      Scale-21 (DASS-21) questionnaire anonymously twice. Firstly, 2-3 weeks before a
      major examination (pre-examination), and secondly, during regular classes (post
      examination). Correlation was sought regarding sex, year of scholarship,
      attendance of a premedical university preparatory program (UPP), housing, and
      smoking. Subjective comments from students were also obtained. RESULTS: A total
      of 76.8% and 74.9% of students participated in pre-and post-examination groups,
      respectively. The majority were the children of expatriate workers in Saudi
      Arabia, and included Arabs, South Asians, and North Americans. Prevalence of
      depression, anxiety, and stress was high (43%, 63%, and 41%, respectively) which
      reduced (to 30%, 47%, and 30%, respectively) to some extent after examinations.
      Saudis and those who had attended UPP had higher DASS-21 scores. Smoking and
      female sex predicted higher levels of "baseline" depression, anxiety, or stress.
      The students perceived the curriculum and schedule to be the primary causes of
      their high DASS-21 scores. CONCLUSION: The students had high "baseline" traits of
      depression, anxiety, and stress, and these were higher if an examination was
      near, especially among Saudis and those who had attended UPP. Smoking and female
      sex predicted higher levels of "baseline" depression, anxiety, or stress.
      Students suggested that study burden and a busy schedule were the major reasons
      for their high DASS-21 scores.

PMID- 26213472
TI  - The reliability and validity of a Chinese-version Short Health Anxiety Inventory:
      an investigation of university students.
AB  - BACKGROUND: The Short Health Anxiety Inventory (SHAI) is widely used in English
      speaking populations, with good reliability and validity. For further research
      needs in the Chinese population, it was translated into a Chinese version
      (CSHAI). Furthermore, the reliability, validity, and cutoff score were examined
      in a nonclinical population in the People's Republic of China. METHODS: Three
      hundred and sixteen undergraduates were evaluated by a set of questionnaires
      including CSHAI, Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating
      Depression Scale (SDS), and the State-Trait Anxiety Inventory (STAI). Fifty-eight
      students completed CSHAI again after 30 days. RESULTS: The two-factor model had
      satisfactory fit indices. The correlation coefficients between each item with the
      CSHAI total and each subscale were between 0.386 and 0.779. The Cronbach's alpha
      coefficients of CSHAI total and its subscales were 0.742, 0.743, and 0.788,
      respectively, and the split-half coefficients were 0.757, 0.788, and 0.912. The
      test-retest correlation coefficients were, respectively, 0.598 (P<0.001), 0.539
      (P<0.001), and 0.691 (P<0.001). Convergent validities were respectively 0.389
      0.453, 0.389-0.410, and 0.250-0.401, and discriminant validities were -5.689
      (P<0.001), -5.614 (P<0.001), and -3.709 (P<0.001). The cutoff score was 15.
      CONCLUSION: CSHAI showed good factor structure, reliability, convergent validity,
      and discriminant validity, and 15 was determined to be the appropriate cutoff
      score for screening health anxiety.

PMID- 26213473
TI  - Clinical predictors for severe sepsis in patients with necrotizing fasciitis: an
      observational cohort study in northern Thailand.
AB  - BACKGROUND: Necrotizing fasciitis (NF) is a life-threatening infection of skin
      and fascia. Its progress is extremely fast, with extensive necrosis. Delay in
      treatment, with subsequent huge soft tissue loss and associated severe sepsis,
      remains a major cause of death in the management of NF. OBJECTIVE: The aim of
      this study was to explore clinical characteristics that may be used to predict
      severe sepsis in patients with NF, in the context of routine clinical practice in
      northern Thailand. METHODS: A retrospective observational cohort study was
      conducted. The patient cohort in this study consisted of all patients who were
      diagnosed with NF by surgical or pathological confirmation. The follow-up period
      started with the admission date and ended with the discharge date. The clinical
      variables were collected from patients registered at three provincial hospitals
      in northern Thailand from 2009 to 2012. The clinical predictors for severe sepsis
      were analyzed using multivariable risk regression. RESULTS: A total of 1,452
      patients were diagnosed with NF, either with severe sepsis (n=237 [16.3%]) or
      without severe sepsis (n=1,215 [83.7%]). From the multivariable analysis, female
      sex (relative risk [RR] =1.51; 95% confidence interval [CI] =1.04-2.20), diabetes
      mellitus (RR =1.40; 95% CI =1.25-1.58), chronic heart disease (RR =1.31; 95% CI
      =1.15-1.49), hemorrhagic bleb (RR =1.47; 95% CI =1.32-1.63), skin necrosis (RR
      =1.45; 95% CI =1.34-1.57), and serum protein <6 g/dL (RR =2.67; 95% CI =1.60
      4.47) were all predictive factors for severe sepsis. CONCLUSION: The clinical
      predictors for severe sepsis in patients with suspicion of NF included female
      sex, diabetes mellitus, chronic heart disease, hemorrhagic bleb, skin necrosis,
      and serum protein <6 d/dL. The risk ratio was much higher in patients with total
      protein less than 6 g/dL, which is associated with malnutrition. Therefore,
      provision of sufficient nutritional support and close monitoring for these
      clinical predictors may be beneficial to reduce morbidity and mortality.

PMID- 26213471
TI  - Role of apolipoprotein E in neurodegenerative diseases.
AB  - Apolipoprotein E (APOE) is a lipid-transport protein abundantly expressed in most
      neurons in the central nervous system. APOE-dependent alterations of the
      endocytic pathway can affect different functions. APOE binds to cell-surface
      receptors to deliver lipids and to the hydrophobic amyloid-beta peptide,
      regulating amyloid-beta aggregations and clearances in the brain. Several APOE
      isoforms with major structural differences were discovered and shown to influence
      the brain lipid transport, glucose metabolism, neuronal signaling,
      neuroinflammation, and mitochondrial function. This review will summarize the
      updated research progress on APOE functions and its role in Alzheimer's disease,
      Parkinson's disease, cardiovascular diseases, multiple sclerosis, type 2 diabetes
      mellitus, Type III hyperlipoproteinemia, vascular dementia, and ischemic stroke.
      Understanding the mutations in APOE, their structural properties, and their
      isoforms is important to determine its role in various diseases and to advance
      the development of therapeutic strategies. Targeting APOE may be a potential
      approach for diagnosis, risk assessment, prevention, and treatment of various
      neurodegenerative and cardiovascular diseases in humans. 

PMID- 26213474
TI  - Prevalence of mental health disorders in inflammatory bowel disease: an
      Australian outpatient cohort.
AB  - BACKGROUND: This study aimed to characterize prevalence of anxiety and depressive
      conditions and uptake of mental health services in an Australian inflammatory
      bowel disease (IBD) outpatient setting. METHODS: Eighty-one IBD patients (39
      males, mean age 35 years) attending a tertiary hospital IBD outpatient clinic
      participated in this study. Disease severity was evaluated according to the
      Manitoba Index. Diagnosis of an anxiety or depressive condition was based upon
      the Mini-International Neuropsychiatric Interview and the Hospital Anxiety and
      Depression Scale. RESULTS: Based on Hospital Anxiety and Depression Scale
      subscale scores >8 and meeting Mini-International Neuropsychiatric Interview
      criteria, 16 (19.8%) participants had at least one anxiety condition, while nine
      (11.1%) had a depressive disorder present. Active IBD status was associated with
      higher prevalence rates across all anxiety and depressive conditions. Generalized
      anxiety was the most common (12 participants, 14.8%) anxiety condition, and major
      depressive disorder (recurrent) was the most common depressive condition reported
      (five participants, 6.2%). Seventeen participants (21%) reported currently
      seeking help for mental health issues while 12.4% were identified has having at
      least one psychological condition but not seeking treatment. CONCLUSION: We
      conclude that rates of anxiety and depression are high in this cohort, and that
      IBD-focused psychological services should be a key component of any holistic IBD
      service, especially for those identified as having active IBD.

PMID- 26213475
TI  - Evaluation of the protein biomarkers and the analgesic response to systemic
      methylene blue in patients with refractory neuropathic pain: a double-blind,
      controlled study.
AB  - AIM: This study was carried out in patients with neuropathic pain in order to
      assess the analgesic effects and changes in protein biomarkers after the
      administration of methylene blue (MB), a diaminophenothiazine with antioxidant
      and anti-inflammatory properties, and with inhibitory effects on nitric oxide.
      MATERIALS AND METHODS: Ten patients with chronic refractory neuropathic pain were
      randomized to receive either MB (10 mg/mL Methylthioninium chloride) 2 mg/kg (MB
      group) or MB 0.02 mg/kg (control group) infused over 60 minutes. Sensory function
      and pain (Numerical Rating Scale) were evaluated at baseline and at 60 minutes
      after the start of the infusion. The patients kept a pain diary during the next
      24 hours and for the following 4 days. Plasma and urinary concentrations of 8
      isoprostane-prostaglandin F2alpha (8-iso-PGF2alpha) and plasma protein biomarkers
      prior to and after the infusions were measured with radioimmunoassay and with
      proximity extension assay. RESULTS: A decrease of the Numerical Rating Scale at
      60 minutes in comparison with baseline was observed in the MB (P=0.047) group.
      The decrease was significant between the MB and the control group on the day of
      and day after MB infusion (P=0.04 and P=0.008, respectively). There was no
      difference in systemic protein expressions between groups except for prolactin
      (PRL) (P=0.02). Three patients demonstrated diminished dynamic mechanical
      allodynia. CONCLUSION: MB decreased the pain levels in patients with chronic
      therapy-resistant neuropathic pain on the first 2 days after administration.
      Known as an endocrine modulator on the anterior pituitary gland, MB infusion
      produced a decrease of PRL. The detailed role of PRL effects in chronic
      neuropathic pain remains undetermined.

PMID- 26213476
TI  - Individually based measurement of temporal summation evoked by a noxious tonic
      heat paradigm.
AB  - BACKGROUND: A model for measuring temporal summation (TS) by tonic noxious
      stimulation was recently proposed. However, methodological variations between
      studies make it difficult to reach a consensus regarding the way TS should be
      applied and calculated. The present study aimed to present a calculation method
      of TS magnitude produced by a tonic heat model in a large cohort of healthy
      subjects. METHODS: Noxious heat stimulation (46.5 degrees C/2 minutes) was
      applied to the forearm of 154 subjects who continuously rated pain intensity
      using a computerized visual analog scale. TS was calculated by "mean group" and
      "individual" approaches. RESULTS: A "typical" pattern of pain response,
      characterized by a peak pain followed by a decrease in intensity to a nadir and
      subsequently a progressive increase in pain scores, was exhibited by 86.4% of the
      subjects. Using the "mean group" and "individual" calculation approaches, the
      mean +/- standard deviation magnitudes of TS were 31.4+/-27.5 and 41.0+/-26.0,
      respectively (P<0.001). Additionally, using the individualized approach, we
      identified a different ("atypical") response pattern among the rest of the
      subjects (13.6%). CONCLUSION: The results support the tonic heat model of TS for
      future utilization. The individualized TS calculation method seems advantageous
      since it better reflects individual magnitudes of TS.

PMID- 26213477
TI  - Factors associated with four or more antenatal care services among pregnant
      women: a cross-sectional survey in eight South Central Coast provinces of
      Vietnam.
AB  - BACKGROUND: In Vietnam, four or more antenatal care (ANC4+) visits/services among
      pregnant women have not been officially reported in the health system. Moreover,
      the factors associated with the use of ANC4+ services have not been studied in
      previous studies. In this study, we conducted an exploratory analysis to identify
      the rate of utilization of ANC4+ services and factors associated with use of
      ANC4+ services among pregnant women in rural areas of Vietnam. METHODS: The study
      was conducted in eight provinces in the South Central Coast region of Vietnam
      between August 2013 and May 2014. A total of 907 women, who delivered in the past
      1 year, participated in the study. Multivariate logistic regression model was
      used to examine the association between all potential factors and utilization of
      ANC4+ services. RESULTS: The rate of utilization of ANC4+ services by women in
      eight South Central Coast provinces was 53.9%. Factors negatively associated with
      using ANC4+ services were belonging to ethnic minority groups having lower
      education, doing informal works, having lower income, having lower knowledge on
      ANC4+ services, and receiving no financial support from the husband. In
      particular, financial support from the husband was considered important in
      improving the use of ANC4+ services by women in rural areas. CONCLUSION: The
      study asserted an inadequacy for ANC4+ utilization and can contribute to missed
      opportunities to achieve better maternal outcomes for women in rural areas of
      Vietnam. The necessity of introducing ANC4+ services in the national guidelines
      on maternal health care should be disseminated to health policy-makers.
      Strategies to increase ANC4+ utilization should focus on knowledge improvement
      and on poor, low-income, and ethnic minority women.

PMID- 26213478
TI  - Phase 1 safety, tolerability, and pharmacokinetic study of single ascending doses
      of XM17 (recombinant human follicle-stimulating hormone) in downregulated healthy
      women.
AB  - BACKGROUND: XM17 is a recombinant human follicle-stimulating hormone (follitropin
      alfa) for stimulation of multifollicular development in women undergoing
      controlled ovarian hyper-stimulation during assisted reproductive therapy and for
      treatment of anovulation. Manufactured using Chinese hamster ovary cells
      transfected with the human follicle-stimulating hormone gene, XM17 has an
      identical amino acid sequence to that of the human protein as well as to those of
      the other approved recombinant human follicle-stimulating hormone products.
      Glycosylation patterns may differ slightly between products. The objectives of
      this first-in-human study were to assess the safety, tolerability,
      pharmacokinetics, and dose-proportionality of single ascending subcutaneous doses
      of XM17 in healthy young female volunteers. METHODS: Endogenous follicle
      stimulating hormone was downregulated by implanting a 1-month depot of goserelin
      acetate 3.6 mg on day 0 in eligible subjects. On day 14 of the experimental
      period, subjects received one of four ascending doses of XM17. Blood sampling to
      obtain the pharmacokinetic profile of XM17 was done at frequent intervals until
      168 hours post-dose. RESULTS: Following downregulation of endogenous follicle
      stimulating hormone to <4 IU/L, 40 subjects (of mean age 29+/-5.4 years) received
      single subcutaneous doses of 37.5 (n=4, pilot group), 75, 150, or 300 IU (n=12
      each) of XM17. The mean serum concentration-time profiles of XM17 revealed dose
      related increases in maximum concentration (Cmax) within 24 hours followed by
      monoexponential decay for the three higher dose levels. Slopes estimated by
      linear regression for Cmax and AUC0-168h were ~1.0 (0.9052 IU/L and 1.0964
      IU.h/L, respectively). For each IU of XM17 administered, Cmax and AUC0-168h rose
      by 0.032 IU/L and 2.60 IU.h/L, respectively. Geometric mean elimination half-life
      ranged from 54 to 90 hours. No antibodies to XM17 were detected. The most common
      treatment-emergent adverse events were headache (12 events in eleven [27.5%]
      subjects) and dizziness (four events in four [10%] subjects); two subjects (5%)
      reported mild pain on touch at the injection site. CONCLUSION: Single
      subcutaneous doses of XM17 up to 300 IU in healthy young women exhibited dose
      proportional pharmacokinetics with good safety and tolerability.

PMID- 26213479
TI  - Knowledge and attitudes of Latin American obstetricians and gynecologists
      regarding intrauterine contraceptives.
AB  - BACKGROUND: Intrauterine contraceptives (IUCs), including the copper intrauterine
      device and the levonorgestrel-releasing intrauterine system (LNG-IUS), are among
      the reversible contraceptive methods with high effectiveness. However, use is low
      in many settings, including some Latin American countries, mainly due to the
      influences of myths, fears, and negative attitudes, not only of users and
      potential users, but also of different cadres of health care professionals. The
      purpose of this study was to assess the knowledge and attitudes of a group of
      Latin American obstetricians and gynecologists regarding IUCs. METHODS: A survey
      was conducted during a scientific meeting organized in Chile in 2014 to present
      and discuss updated information about contraception. Obstetricians and
      gynecologists from 12 Latin American countries, who reported that they provide
      daily contraception services in both the public and private sectors, participated
      in the meeting. Participants who agreed to take part in the survey responded to a
      multiple-choice questionnaire on issues regarding knowledge, use, and attitudes
      about IUCs. RESULTS: Of the 210 obstetricians and gynecologists participating in
      the meeting, the respondents to each question varied from 168 (80.0%) to 205
      (97.6%). Almost 50% recognized that the failure rate of combined oral
      contraceptives, patches, and vaginal rings is 8%-10%. Furthermore, 10% of the
      participants did not recognize the high contraceptive effectiveness of long
      acting reversible contraceptive methods. Additionally, almost 80% of the
      respondents answered that they did not offer IUCs to nulligravidas and almost 10%
      did not offer IUCs to adolescents, albeit almost 90% of the respondents reported
      that nulligravidas are candidates for an LNG-IUS. CONCLUSION: Some deficiencies
      and contradictions in terms of knowledge and attitudes were identified from the
      answers of the Latin American obstetricians and gynecologists who participated in
      the survey. The knowledge and attitudes of health care professionals about IUCs
      are important in order to provide adequate counseling and to expand the use of
      IUCs.

PMID- 26213480
TI  - The Outcomes and Experiences Questionnaire: development and validation.
AB  - BACKGROUND: This report presents evidence regarding the development and
      validation of a new questionnaire, the Outcomes and Experiences Questionnaire
      (OEQ). The rationale for the questionnaire is to bring together into one short
      instrument questions about two distinct domains - patients' reports of the
      outcomes of their care and how they experience care. METHODS: The OEQ was
      developed from literature reviews, iterative drafting and discussion within the
      research group and cognitive testing with a sample of patients who had a hospital
      experience. Two validation studies were carried out with an eleven item OEQ. The
      goals of the studies were to examine response rates and to test specific
      hypotheses of how OEQ should relate to other variables normally collected in the
      two studies. In the first study, the OEQ was added to the follow-up
      questionnaires for patients (n=490) receiving surgery for hip or knee replacement
      or varicose vein procedures participating in the national Patient Reported
      Outcome Measures (PROMs) program permitting the analysis of the OEQ against
      change scores for the measures obtained before and after surgery. In the second
      study the OEQ was included in a sample of patients (n=586) who had been selected
      to receive the National Health Service (NHS) inpatient survey from three
      contrasting hospital trusts. RESULTS: Results from study one provided consistent
      and substantial evidence of construct validity of OEQ particularly for those
      receiving hip or knee replacement. The OEQ sub-scales behaved differently and as
      predicted against other PROMs variables. Again hypotheses of how the two sub
      scales regarding outcomes and experiences would relate to the existing domains of
      patient experience in the inpatient survey were broadly confirmed in study two.
      CONCLUSION: The report provides encouraging evidence of the OEQ's capacity to
      assess distinct reports from patients about outcomes and experiences of care
      within a single short questionnaire.

PMID- 26213481
TI  - Characteristics and lessons learned from practice-based research networks (PBRNs)
      in the United States.
AB  - Practice-based research networks (PBRNs) are organizations that involve
      practicing clinicians in asking and answering clinically relevant research
      questions. This review explores the origins, characteristics, funding, and
      lessons learned through practice-based research in the United States. Primary
      care PBRNs emerged in the USA in the 1970s. Early studies explored the etiology
      of common problems encountered in primary care practices (eg, headache,
      miscarriage), demonstrating the gap between research conducted in controlled
      specialty settings and real-world practices. Over time, national initiatives and
      an evolving funding climate have shaped PBRN development, contributing to larger
      networks, a push for shared electronic health records, and the use of a broad
      range of research methodologies (eg, observational studies, pragmatic randomized
      controlled trials, continuous quality improvement, participatory methods). Today,
      there are over 160 active networks registered with the Agency for Healthcare
      Research and Quality's PBRN Resource Center that engage primary care clinicians,
      pharmacists, dentists, and other health care professionals in research and
      quality-improvement initiatives. PBRNs provide an important laboratory for
      encouraging collaborative research partnerships between academicians and
      practices or communities to improve population health, conduct comparative
      effectiveness and patient-centered outcomes research, and study health policy
      reform. PBRNs continue to face critical challenges that include: (1) adapting to
      a changing landscape; (2) recruiting and retaining membership; (3) securing
      infrastructure support; (4) straddling two worlds (academia and community) and
      managing expectations; and (5) preparing for workforce transitions.

PMID- 26213482
TI  - Sociodemographic differences in parental satisfaction with an autism spectrum
      disorder diagnosis.
AB  - BACKGROUND: The diagnostic process for autism spectrum disorder (ASD) can be
      difficult for families. Growing evidence suggests that the diagnostic process may
      vary as a function of sociodemographic factors, such as socioeconomic status. The
      purpose of this study was to extend findings related to families' experiences
      obtaining a diagnosis and accessing services for their young child with ASD.
      METHOD: A mixed methods approach was used in this study, in which 46 families
      with children with ASD participated. A chi-square analysis compared ratings of
      parental satisfaction with the diagnostic process and current services between
      sociodemographic groups, and this was supplemented by thematic analysis of
      relevant open-ended questions. RESULTS: Results indicated that satisfaction
      ratings varied significantly by maternal education and family income levels.
      Ratings of satisfaction with the child's paediatrician also differed by family
      income. Major themes from the open-ended questions are discussed. CONCLUSIONS:
      Results support assessing satisfaction and barriers in families seeking
      healthcare and school-based services to facilitate access to services.

PMID- 26213483
TI  - Direct Arylation of Benzo[b]furan and Other Benzo-Fused Heterocycles.
AB  - The direct arylation of benzo[b]furan, benzo[b]thiophene, and indole has been
      studied by using aromatic bromides as the aryl source. The protocol employing
      common reagents and a Pd catalyst has led to the regioselective arylation of
      these heterocycles at the 2-position. A range of functional groups were
      tolerated, providing quick access to a variety of arylated benzo-fused
      heterocycles that would be accessible more elaborately using classical synthetic
      strategies. This is the first systematic study of the direct arylation of
      benzo[b]furan.

PMID- 26213484
TI  - Crossed McMurry Coupling Reactions for Porphycenic Macrocycles: Non-Statistical
      Selectivity and Rationalisation.
AB  - Crossed McMurry reactions of bifuran- or bithiophenedicarbaldehydes with
      bipyrroledicarbaldehydes have been studied for the first time. Only those
      porphycenic macrocycles derived from homocoupled McMurry products were formed.
      The results are explained by using both density functional theory and electron
      propagator computations to model the electron affinity of the dialdehyde starting
      materials. It was predicted that bifuran?bithiophene cross-coupling would indeed
      occur, and this was demonstrated by the first synthesis of a novel dioxa,dithio
      hetero-porphycenoid annulene. This approach will allow the prior identification
      of viable substrates for related crossed McMurry reactions.

PMID- 26213485
TI  - Selective Formation of Trimethylene Carbonate (TMC): Atmospheric Pressure Carbon
      Dioxide Utilization.
AB  - Carbon dioxide utilisation (CDU) is currently gaining increased interest due to
      the abundance of CO2 and its possible application as a C1 building block. We
      herein report the first example of atmospheric pressure carbon dioxide
      incorporation into oxetane to selectively form trimethylene carbonate (TMC),
      which is a significant challenge as TMC is thermodynamically less favoured than
      its corresponding co-polymer.

PMID- 26213490
TI  - Weak annihilation and new physics in charmless [Formula: see text] decays.
AB  - We use currently available data of nonleptonic charmless 2-body [Formula: see
      text] decays ([Formula: see text]) that are mediated by [Formula: see text] QCD-
      and QED-penguin operators to study weak annihilation and new-physics effects in
      the framework of QCD factorization. In particular we introduce one weak
      annihilation parameter for decays related by [Formula: see text] quark
      interchange and test this universality assumption. Within the standard model, the
      data supports this assumption with the only exceptions in the [Formula: see text]
      system, which exhibits the well-known "[Formula: see text] puzzle", and some
      tensions in [Formula: see text]. Beyond the standard model, we simultaneously
      determine weak-annihilation and new-physics parameters from data, employing model
      independent scenarios that address the "[Formula: see text] puzzle", such as QED
      penguins and [Formula: see text] current-current operators. We discuss also
      possibilities that allow further tests of our assumption once improved
      measurements from LHCb and Belle II become available.

PMID- 26213491
TI  - How The Genome Got a Life Span.
AB  - In the space of little more than a decade, ideas of the human genome have shifted
      significantly, with the emergence of the notion that the genome an individual
      changes with development, age, disease, environmental inputs, and time. This
      paper examines the emergence of the genome with a life span, one that experiences
      drift, instability and mutability, and a host of other temporal changes. We argue
      that developments in chromatin biology have provided the basis for this genomic
      embodiment of experience and exposure. We analyze how time has come to matter for
      the genome through chromatin, providing analysis of examples in which the human
      life course is being explored as a set of material changes to chromatin. A genome
      with a lifespan aligns the molecular and the experiential in new ways, shifting
      ideas of life stages, their interrelation, and the temporality of health and
      disease.

PMID- 26213492
TI  - Is the Returning Farmland to Forest Program a Success? Three Case Studies from
      Sichuan.
AB  - China's tuigeng huanlin or "Returning Farmland to Forest" (RFFP) program has been
      widely praised as the world's largest and most successful payment for ecosystem
      services program, as well as a major contributor to China's dramatic increase in
      forest cover from perhaps as low as 8% in 1960 to about 21% today. By
      compensating rural households for the conversion of marginal farmland to
      forestland and financing the afforestation of barren mountainsides, the program,
      in addition to expanding forestland, aims to reduce soil erosion and alleviate
      poverty. This paper presents qualitative and quantitative studies conducted on
      the local implementation of RFFP in three diverse townships in Sichuan. We find
      the actual results to be more mixed than the official figures would indicate.
      Though there have been some positive results, we identify problems with site and
      species selection, compensation for land taken out of cultivation, shift of labor
      to off-farm activities, and monitoring of replanted sites, which challenge the
      ecological and economic impacts of these programs and reveal much of the effort
      of the program has been misdirected. We suggest that efforts are misplaced
      because of the top-down, panacea nature of the program, which in turn is a
      feature of Chinese bureaucratic management.

PMID- 26213493
TI  - Decolorization of RhB dye by manganese oxides: effect of crystal type and
      solution pH.
AB  - BACKGROUND: Organic dye pollution in water has become a major source of
      environmental pollution. Mn(III/IV) oxides have attracted a great deal of
      attention to remove organic dye pollutants due to their unique structures and
      physicochemical properties. Numerous studies have reported the removal of dye by
      various Mn(III/IV) oxides through catalytic degradation and adsorption. The
      crystalline structures of manganese oxides and solution pH may exert substantial
      impact on the removal of dyes. However, few studies have focused on the oxidative
      degradation of RhB dye using Mn(III/IV) oxides with different crystal structures
      during a spontaneous reaction. In the present study, three manganese oxides with
      different crystal type (alpha-MnO2, beta-MnO2, and delta-MnO2) were prepared by
      refluxing process to decolorize RhB dye in various pH solutions. RESULTS: The
      results showed that the decolorization efficiencies of RhB for the three
      manganese oxides all increase with decrease solution pH. alpha-MnO2 exhibited
      highest activity and could efficiently degrade RhB at pH 2-6. The degradation of
      RhB by beta-MnO2 and delta-MnO2 could be observed at pH 2-3, and only little
      adsorption RhB on manganese oxides could be found at pH 4-6. The UPLC/MS analysis
      suggests that the decolorization of RhB by manganese oxides consists of three
      main stages: (1) cleavage of the ethyl groups from RhB molecular to form Rh; (2)
      further destruction of -COOH and -CNH2 from Rh to form the small molecular
      substances; (3) mineralization of the small molecular substances into CO2, H2O,
      NO3 (-) and NH4 (+). CONCLUSIONS: Overall, these results indicate that alpha-MnO2
      may be envisaged as efficient oxidants for the treatment of organic dye
      containing wastewater under acid conditions.

PMID- 26213494
TI  - GSK3beta mediates pancreatic cancer cell invasion in vitro via the CXCR4/MMP-2
      Pathway.
AB  - BACKGROUND: Glycogen synthase kinase-3beta (GSK3beta) expression and activity are
      upregulated in pancreatic cancer tissues. In our previous study, we found that
      stromal cell-derived factor-1/ chemokine receptor C-X-C motif chemokine receptor
      4 (SDF-1alpha/CXCR4) upregulated matrix metalloproteinase 2 (MMP-2) and promoted
      invasion in PANC1 and SW-1990 pancreatic cancer cells by activating p38 mitogen
      activated protein kinase (p38 MAPK). Additionally, inhibition of GSK3beta reduced
      MMP-2 secretion. METHODS: To investigate the molecular mechanism of GSK3beta in
      pancreatic cancer tissues, we created stable PANC1 cells up-regulation of
      GSK3beta by transfecting GSK3beta overexpression plasmid, and down-regulation of
      GSK3beta using two different types of RNA interference. RESULTS: Western blotting
      showed that overexpression of GSK3beta up-regulated CXCR4 and MMP-2 expression;
      suppression of GSK3beta down-regulated CXCR4 and MMP-2 protein expression. Up
      regulation of MMP2 induced by overexpression of GSK3beta was blocked by
      inhibition of CXCR4. Overexpression of GSK3beta promoted PANC1 cell invasion, and
      down-regulation of GSK3beta suppressed PANC1 cell invasion in the transwell
      invasion assays. However, inhibition of CXCR4 using shRNA attenuated the ability
      of GSK3beta to promote PANC1 cell invasion. CONCLUSIONS: This study demonstrated
      that GSK3beta promotes PANC1 cell invasion via the CXCR4/MMP-2 pathway.

PMID- 26213495
TI  - Association between IL-18 polymorphisms, serum levels, and HBV-related
      hepatocellular carcinoma in a Chinese population: a retrospective case-control
      study.
AB  - BACKGROUND: Interleukin (IL)-18 gene polymorphisms have been found to play
      multiple roles in various diseases. However, studies focused on its involvement
      in hepatocellular carcinoma (HCC) remains controversial, and no much study has
      taken IL-18 serum levels into consideration. This study investigates the
      association between IL-18 polymorphisms and risk of hepatitis B virus-related HCC
      and their impact on serum IL-18 serum levels. METHODS: A total of 153 patients
      and 165 healthy controls were enrolled in this study. Polymorphisms at positions 
      607C/A and -137G/C in the IL-18 gene were determined using the polymerase chain
      reaction-restriction fragment length polymorphism method. Serum IL-18 levels were
      determined with an ELISA kit. RESULTS: No relationship was found between the 
      607C/A polymorphism and an individual's susceptibility to HCC. For the -137G/C
      polymorphism, the GC genotype and C allele were found to be significantly
      associated with decreased HCC risk (OR 0.506, 95% CI 0.290-0.882, P = 0.016 and
      OR 0.520, 95% CI 0.332-0.814, P = 0.004, respectively). The A(-607)C(-137)
      haplotype was also associated with a significant decreased risk of HCC (OR 0.495,
      95% CI 0.294-0.834, P = 0.007). Serum IL-18 levels were found to be significantly
      lower in HCC patients compared to the control group in both the overall
      population and subjects with the different SNPs. Further, no association was
      found between serum IL-18 levels and the different genotypes within the same SNP.
      CONCLUSION: These findings suggest that the -137G/C SNP in IL-18 may be a
      protective factor against HCC. Nevertheless, none of the studied SNPs was
      associated with the expression of IL-18.

PMID- 26213496
TI  - Overexpression of MALT1-A20-NF-kappaB in adult B-cell acute lymphoblastic
      leukemia.
AB  - BACKGROUND: A20 is a dual inhibitor of NF-kappaB activation and apoptosis in the
      tumor necrosis factor receptor 1 signaling pathway, and both are related to
      tumorigenesis. A20 is frequently inactivated by deletions and/or mutations in
      several B and T cell lymphoma subtypes; however, knowledge of the role of A20 in
      B-cell acute lymphoblastic leukemia (B-ALL) remains limited. In this study, we
      characterized the A20 gene expression pattern, the expression level of its
      upstream regulating factor MALT1, and its downstream target NF-kappaB in adult B
      ALL. METHODS: The expression level of MALT1, A20 and NF-kappaB1 was detected in
      peripheral blood mononuclear cells (PBMCs) from 20 patients with adult B-ALL
      (including 12 de novo B-ALL and 8 refractory/relapse B-ALL cases), and nine
      patients with B-ALL in complete remission (CR) using real-time PCR. Sixteen
      healthy individuals served as controls. RESULTS: Significant A20 overexpression
      was found in the B-ALL (median: 13.489) compared with B-ALL CR (median: 3.755) (P
      = 0.003) patients and healthy individuals (median: 8.748) (P = 0.002), while
      there was no significant difference in A20 expression between B-ALL CR patients
      and healthy individuals (P = 0.107). Interestingly, the A20 expression level in
      the B-ALL samples was relatively different with approximately 50% of the B-ALL
      cases showing a relatively high A20 expression level, while the remaining 50%
      cases demonstrated slight upregulation or a similar expression level as the
      healthy controls. However, there was no significant difference in the A20
      expression level between de novo B-ALL (median 12.252) and refractory/relapse B
      ALL patients (median 21.342) (P = 0.616). Similarly, a significantly higher
      expression level of NF-kappaB1 was found in the B-ALL (median 1.062) patients
      compared with healthy individuals (median 0.335) (P < 0.0001), while the NF
      kappaB1 expression level was downregulated in the B-ALL CR group (median 0.339),
      which was significantly lower than that in those with B-ALL (P = 0.001).
      Moreover, the MALT1 expression level in B-ALL was upregulated (median 1.938) and
      significantly higher than that in healthy individuals (median 0.677) (P = 0.002)
      and B-ALL CR patients (median 0.153) (P = 0.008). The correlation of the
      expression levels of all three genes was lost in B-ALL. CONCLUSIONS: We found
      that MALT1-A20-NF-kappaB is overexpressed in adult B-ALL, which may be related to
      the pathogenesis of B-ALL, and this pathway may be considered a potentially
      attractive target for the development of B-ALL therapeutics.

PMID- 26213497
TI  - The perception of allergen-specific immunotherapy among pediatricians in the
      primary care setting.
AB  - BACKGROUND: Allergic respiratory diseases are constantly increasing in
      prevalence. Allergen Immunotherapy (AIT) represent a valuable therapeutic tool as
      symptomatic and preventative approach, expecially in children. In Italy, primary
      care pediatricians (PCP) represent the first-line contact and interface for
      prescription, use and management of AIT. We attempted to evaluate the perception
      of AIT practice among PCP. METHODS: A questionnaire was built-up, based on
      literature, guidelines and with the contribution of pediatricians. The
      questionnaire, including 12 items, was e-mailed to 180 PCP, randomly chosen from
      mailing lists. The questionnaire explored the personal perception of AIT, the
      comparison between subcutaneous and sublingual AIT and the overall awareness
      about the treatment. RESULTS: 130 questionnaires were eligible for analysis.
      There was a satisfactory knowledge of the characteristics of AIT, its aims and
      limits, although the positioning of the treatment in guidelines was
      insufficiently known. Overall, the prescription of AIT made by other specialists
      was accepted and agreed (78 %). The majority of pediatricians felt that a more
      intense divulgation and information about AIT would be needed (90 %). CONCLUSION:
      AIT is in general well known and accepted among PCP, although a more intense
      divulgation effort is required.

PMID- 26213499
TI  - A new turbidimetric immunoassay for serum calprotectin for fully automatized
      clinical analysers.
AB  - Serum and plasma calprotectin concentration is shown to be elevated when
      neutrophils are activated, and may therefore be used as a marker for inflammatory
      diseases. A serum calprotectin immunoassay was developed based on calprotectin
      values observed in samples from the intensive care unit. The polyclonal avian
      antibodies were raised and affinity purified with calprotectin antigens. The
      performance was tested and it was observed that the assay was linear in the range
      0.3-24.7 mg/L, the limit of quantitation was observed to be lower than 0.3 mg/L,
      no antigen excess was observed up to 54 mg/L, all CVs were lower than 1.8 % in
      the precision study, the calibration curve stability was longer than 6 weeks, and
      there was no significant interference detected for haemoglobin, intralipid or
      bilirubin. The serum calprotectin immunoassay presented in this paper performs
      well within the criteria carefully set from the limited clinical experience
      obtained in both serum and plasma. In addition it is commutable with Buhlmann
      MRP8/14 ELISA. 

PMID- 26213501
TI  - Research articles, labels, and prestige.

PMID- 26213500
TI  - Collateral Report of Psychopathy: Convergent and Divergent Validity of the
      Psychopathic Personality Inventory-Short Form.
AB  - Psychopathy is a personality syndrome comprised of interpersonal, affective, and
      behavioral features that has emerged as a correlate of intimate partner violence
      perpetration. One commonly used self-report measure of psychopathy is the
      Psychopathic Personality Inventory-Short Form. The current study employed a multi
      trait, multi-method approach to test convergent and discriminant validity of the
      measure in partner-violent couples by comparing males' self-report of psychopathy
      to the informant report of their female partner (N = 114). It was hypothesized
      that the female partner-report of the male's psychopathy would be highly
      correlated with the male report of his own psychopathy, thus providing evidence
      for the construct validity and interrater reliability of the PPI-SF. Analyses
      found that male and female reports were correlated significantly on the two major
      factors of the PPI-SF. Furthermore, the female-report explained a significant
      amount of variance over and above men's self-report on PAI scales designed to
      indicate antisocial personality traits.

PMID- 26213502
TI  - Keywords, discoverability, and impact.

PMID- 26213498
TI  - Coupled cell networks are target cells of inflammation, which can spread between
      different body organs and develop into systemic chronic inflammation.
AB  - Several organs in the body comprise cells coupled into networks. These cells have
      in common that they are excitable but do not express action potentials.
      Furthermore, they are equipped with Ca(2+) signaling systems, which can be
      intercellular and/or extracellular. The transport of small molecules between the
      cells occurs through gap junctions comprising connexin 43. Examples of cells
      coupled into networks include astrocytes, keratinocytes, chondrocytes, synovial
      fibroblasts, osteoblasts, connective tissue cells, cardiac and corneal
      fibroblasts, myofibroblasts, hepatocytes, and different types of glandular cells.
      These cells are targets for inflammation, which can be initiated after injury or
      in disease. If the inflammation reaches the CNS, it develops into
      neuroinflammation and can be of importance in the development of systemic chronic
      inflammation, which can manifest as pain and result in changes in the expression
      and structure of cellular components. Biochemical parameters of importance for
      cellular functions are described in this review. 

PMID- 26213503
TI  - A personalized approach to deliver health care information to diabetic patients
      in community care clinics.
AB  - OBJECTIVE: The study's purpose was to test the generalizability of an
      individualized information prescription model, which has been previously
      validated for educating patients about hypertension in emergency department and
      community health center settings. Study investigators assessed the effects of
      educational materials targeted to health literacy levels and learning styles on
      patients' diabetes knowledge in a community clinic setting. METHODS: From May to
      August 2012, 160 patients were recruited and randomized into intervention (n =
      81) and control (n = 79) groups. Inclusion criteria included 18 years or older,
      English or Spanish speaker, and a type 2 diabetes diagnosis. Measures included
      modified versions of the Diabetes Knowledge Test and Subjective Numeracy Scale,
      along with brief health literacy and learning style assessments. Study team
      members contacted both groups after 2 and 6 weeks to reassess diabetes knowledge.
      RESULTS: The control group showed no significant change in diabetes knowledge at
      both follow-ups. In contrast, the mean number of diabetes knowledge questions
      answered correctly by the intervention group increased significantly after 2
      weeks (Delta = 2.66, P = 0.000), which persisted at 6 weeks (Delta = 2.46, P =
      0.00). CONCLUSIONS: This study showed that patients' knowledge about diabetes
      increased significantly after exposure to educational materials targeted to their
      health literacy levels and learning style preferences and that the model is
      transferrable among health conditions.

PMID- 26213504
TI  - Starting the data conversation: informing data services at an academic health
      sciences library.
AB  - OBJECTIVE: The research obtained information to plan data-related products and
      services. METHODS: Biomedical researchers in an academic medical center were
      selected using purposive sampling and interviewed using open-ended questions
      based on a literature review. Interviews were conducted until saturation was
      achieved. RESULTS: Interview responses informed library planners about
      researchers' key data issues. CONCLUSIONS: This approach proved valuable for
      planning data management products and services and raising library visibility
      among clients in the research data realm.

PMID- 26213505
TI  - Retraction policies of top scientific journals ranked by impact factor.
AB  - OBJECTIVE: This study gathered information about the retraction policies of the
      top 200 scientific journals, ranked by impact factor. METHODS: Editors of the top
      200 science journals for the year 2012 were contacted by email. RESULTS: One
      hundred forty-seven journals (74%) responded to a request for information. Of
      these, 95 (65%) had a retraction policy. Of journals with a retraction policy,
      94% had a policy that allows the editors to retract articles without authors'
      consent. CONCLUSIONS: The majority of journals in this sample had a retraction
      policy, and almost all of them would retract an article without the authors'
      permission.

PMID- 26213506
TI  - Analysis of reference sources used in drug-related Wikipedia articles.
AB  - OBJECTIVE: References from drug-related Wikipedia articles and a drug information
      database were compared. METHODS: Drugs in Food and Drug Administration (FDA)
      MedWatch alerts from January-July 2013 were searched in Wikipedia and Lexicomp to
      compare reference types and to assess the time for drug safety information to be
      incorporated into Wikipedia articles. RESULTS: Wikipedia most commonly cited peer
      reviewed journal articles (49.2%) and news articles (12.0%). MedWatch citations
      were incorporated into Wikipedia on average in 5.9 days. CONCLUSIONS: Wikipedia
      cited various sources but may not be a reliable, up-to-date resource for drug
      safety information.

PMID- 26213507
TI  - An extensible and successful method of identifying collaborators for National
      Library of Medicine informationist projects.
AB  - QUESTION/PURPOSE: The New York University (NYU) Health Sciences Library used a
      new method to arrange in-depth discussions with basic science researchers. The
      objective was to identify collaborators for a new National Library of Medicine
      administrative supplement. SETTING: The research took place at the NYU Health
      Sciences Library. METHODS: Using the National Institutes of Health (NIH)
      RePORTER, forty-four researchers were identified and later contacted through
      individualized emails. RESULTS: Nine researchers responded to the email followed
      by six in-person or phone discussions. At the conclusion of this process, two
      researchers submitted applications for supplemental funding, and both of these
      applications were successful. CONCLUSIONS: This method confirmed these users
      could benefit from the skills and knowledge of health sciences librarians, but
      they are largely unaware of this.

PMID- 26213508
TI  - Bias and other limitations affect measures of journals in integrative and
      complementary medicineKa-wai Fan, PhD.
AB  - Publishing articles in a prestigious journal is a golden rule for university
      professors and researchers nowadays. Impact factor, journal rank, and citation
      count, included in Science Citation Index managed by Thomson Reuters Web of
      Science, are the most important indicators for evaluating the quality of academic
      journals. By listing the journals encompassed in the "Integrative and
      Complementary Medicine" category of Science Citation Index from 2003 to 2013,
      this paper examines the publication trends of journals in the category. The
      examination includes number, country of origin, ranking, and languages of
      journals. Moreover, newly listed or removed journals in the category, journal
      publishers, and open access strategies are examined. It is concluded that the
      role of journal publisher should not be undermined in the "Integrative and
      Complementary Medicine" category. 

PMID- 26213509
TI  - Bloom's taxonomy of cognitive learning objectives.
AB  - Information professionals who train or instruct others can use Bloom's taxonomy
      to write learning objectives that describe the skills and abilities that they
      desire their learners to master and demonstrate. Bloom's taxonomy differentiates
      between cognitive skill levels and calls attention to learning objectives that
      require higher levels of cognitive skills and, therefore, lead to deeper learning
      and transfer of knowledge and skills to a greater variety of tasks and contexts. 

PMID- 26213510
TI  - Research data management.

PMID- 26213511
TI  - Michelle Kraft, AHIP, Medical Library Association President, 2015-2016.

PMID- 26213512
TI  - Cognitive Interviews Conducted in Spanish: A Method for Enhancing a Hispanic
      Infant Feeding Questionnaire.
AB  - Research indicates that using cognitive interview techniques, that are
      qualitative in nature, can enhance the quality of health survey instruments. This
      study was conducted during the formative phase of the Un Bebe Saludable: Un
      Regalo Muy Especial (A Healthy Baby: A Very Special Gift) program. Cognitive
      interviews were conducted in Spanish in an effort to improve the quality of a
      Hispanic infant feeding behavior survey designed to evaluate a peer education
      program for Latina mothers participating in the Special Supplemental Nutrition
      Program for Women, Infants, and Children (WIC). Results indicate that a small
      sample of cognitive interviews can improve the level of question comprehension
      and the ease at which respondents can process the information from specific
      survey items. Our experience suggests that adding cognitive interviewing to
      conventional field pre-testing and back-translation techniques during the
      development of Hispanic health surveys may enhance the quality of the health
      behavior data that are generated.

PMID- 26213513
TI  - NAIRAS aircraft radiation model development, dose climatology, and initial
      validation.
AB  - [1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is
      a real-time, global, physics-based model used to assess radiation exposure to
      commercial aircrews and passengers. The model is a free-running physics-based
      model in the sense that there are no adjustment factors applied to nudge the
      model into agreement with measurements. The model predicts dosimetric quantities
      in the atmosphere from both galactic cosmic rays (GCR) and solar energetic
      particles, including the response of the geomagnetic field to interplanetary
      dynamical processes and its subsequent influence on atmospheric dose. The focus
      of this paper is on atmospheric GCR exposure during geomagnetically quiet
      conditions, with three main objectives. First, provide detailed descriptions of
      the NAIRAS GCR transport and dosimetry methodologies. Second, present a
      climatology of effective dose and ambient dose equivalent rates at typical
      commercial airline altitudes representative of solar cycle maximum and solar
      cycle minimum conditions and spanning the full range of geomagnetic cutoff
      rigidities. Third, conduct an initial validation of the NAIRAS model by comparing
      predictions of ambient dose equivalent rates with tabulated reference measurement
      data and recent aircraft radiation measurements taken in 2008 during the minimum
      between solar cycle 23 and solar cycle 24. By applying the criterion of the
      International Commission on Radiation Units and Measurements (ICRU) on acceptable
      levels of aircraft radiation dose uncertainty for ambient dose equivalent greater
      than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the
      measured data, which fall within the ICRU acceptable uncertainty limit of 30%.
      The NAIRAS model predictions of ambient dose equivalent rate are generally within
      50% of the measured data for any single-point comparison. The largest differences
      occur at low latitudes and high cutoffs, where the radiation dose level is low.
      Nevertheless, analysis suggests that these single-point differences will be
      within 30% when a new deterministic pion-initiated electromagnetic cascade code
      is integrated into NAIRAS, an effort which is currently underway.

PMID- 26213514
TI  - Space Weather Observations by GNSS Radio Occultation: From FORMOSAT-3/COSMIC to
      FORMOSAT-7/COSMIC-2.
AB  - The joint Taiwan-United States FORMOSAT-3/COSMIC (Constellation Observing System
      for Meteorology, Ionosphere, and Climate) mission, hereafter called COSMIC, is
      the first satellite constellation dedicated to remotely sense Earth's atmosphere
      and ionosphere using a technique called Global Positioning System (GPS) radio
      occultation (RO). The occultations yield abundant information about neutral
      atmospheric temperature and moisture as well as space weather estimates of slant
      total electron content, electron density profiles, and an amplitude scintillation
      index, S4. With the success of COSMIC, the United States and Taiwan are moving
      forward with a follow-on RO mission named FORMOSAT-7/COSMIC-2 (COSMIC-2), which
      will ultimately place 12 satellites in orbit with two launches in 2016 and 2019.
      COSMIC-2 satellites will carry an advanced Global Navigation Satellite System
      (GNSS) RO receiver that will track both GPS and Russian Global Navigation
      Satellite System signals, with capability for eventually tracking other GNSS
      signals from the Chinese BeiDou and European Galileo system, as well as secondary
      space weather payloads to measure low-latitude plasma drifts and scintillation at
      multiple frequencies. COSMIC-2 will provide 4-6 times (10-15X in the low
      latitudes) the number of atmospheric and ionospheric observations that were
      tracked with COSMIC and will also improve the quality of the observations. In
      this article we focus on COSMIC/COSMIC-2 measurements of key ionospheric
      parameters.

PMID- 26213516
TI  - The main pillar: Assessment of space weather observational asset performance
      supporting nowcasting, forecasting, and research to operations.
AB  - : Space weather forecasting critically depends upon availability of timely and
      reliable observational data. It is therefore particularly important to understand
      how existing and newly planned observational assets perform during periods of
      severe space weather. Extreme space weather creates challenging conditions under
      which instrumentation and spacecraft may be impeded or in which parameters reach
      values that are outside the nominal observational range. This paper analyzes
      existing and upcoming observational capabilities for forecasting, and discusses
      how the findings may impact space weather research and its transition to
      operations. A single limitation to the assessment is lack of information provided
      to us on radiation monitor performance, which caused us not to fully assess
      (i.e., not assess short term) radiation storm forecasting. The assessment finds
      that at least two widely spaced coronagraphs including L4 would provide
      reliability for Earth-bound CMEs. Furthermore, all magnetic field measurements
      assessed fully meet requirements. However, with current or even with near term
      new assets in place, in the worst-case scenario there could be a near-complete
      lack of key near-real-time solar wind plasma data of severe disturbances heading
      toward and impacting Earth's magnetosphere. Models that attempt to simulate the
      effects of these disturbances in near real time or with archival data require
      solar wind plasma observations as input. Moreover, the study finds that near
      future observational assets will be less capable of advancing the understanding
      of extreme geomagnetic disturbances at Earth, which might make the resulting
      space weather models unsuitable for transition to operations. KEY POINTS:
      Manuscript assesses current and near-future space weather assetsCurrent assets
      unreliable for forecasting of severe geomagnetic stormsNear-future assets will
      not improve the situation.

PMID- 26213515
TI  - Two-step forecast of geomagnetic storm using coronal mass ejection and solar wind
      condition.
AB  - To forecast geomagnetic storms, we had examined initially observed parameters of
      coronal mass ejections (CMEs) and introduced an empirical storm forecast model in
      a previous study. Now we suggest a two-step forecast considering not only CME
      parameters observed in the solar vicinity but also solar wind conditions near
      Earth to improve the forecast capability. We consider the empirical solar wind
      criteria derived in this study (Bz  <= -5 nT or Ey  >= 3 mV/m for t>= 2 h for
      moderate storms with minimum Dst less than -50 nT) and a Dst model developed by
      Temerin and Li (2002, 2006) (TL model). Using 55 CME-Dst pairs during 1997 to
      2003, our solar wind criteria produce slightly better forecasts for 31 storm
      events (90%) than the forecasts based on the TL model (87%). However, the latter
      produces better forecasts for 24 nonstorm events (88%), while the former
      correctly forecasts only 71% of them. We then performed the two-step forecast.
      The results are as follows: (i) for 15 events that are incorrectly forecasted
      using CME parameters, 12 cases (80%) can be properly predicted based on solar
      wind conditions; (ii) if we forecast a storm when both CME and solar wind
      conditions are satisfied (?), the critical success index becomes higher than that
      from the forecast using CME parameters alone, however, only 25 storm events (81%)
      are correctly forecasted; and (iii) if we forecast a storm when either set of
      these conditions is satisfied (?), all geomagnetic storms are correctly
      forecasted.

PMID- 26213517
TI  - MAG4 versus alternative techniques for forecasting active region flare
      productivity.
AB  - : MAG4 is a technique of forecasting an active region's rate of production of
      major flares in the coming few days from a free magnetic energy proxy. We present
      a statistical method of measuring the difference in performance between MAG4 and
      comparable alternative techniques that forecast an active region's major-flare
      productivity from alternative observed aspects of the active region. We
      demonstrate the method by measuring the difference in performance between the
      "Present MAG4" technique and each of three alternative techniques, called
      "McIntosh Active-Region Class," "Total Magnetic Flux," and "Next MAG4." We do
      this by using (1) the MAG4 database of magnetograms and major flare histories of
      sunspot active regions, (2) the NOAA table of the major-flare productivity of
      each of 60 McIntosh active-region classes of sunspot active regions, and (3) five
      technique performance metrics (Heidke Skill Score, True Skill Score, Percent
      Correct, Probability of Detection, and False Alarm Rate) evaluated from 2000
      random two-by-two contingency tables obtained from the databases. We find that
      (1) Present MAG4 far outperforms both McIntosh Active-Region Class and Total
      Magnetic Flux, (2) Next MAG4 significantly outperforms Present MAG4, (3) the
      performance of Next MAG4 is insensitive to the forward and backward temporal
      windows used, in the range of one to a few days, and (4) forecasting from the
      free-energy proxy in combination with either any broad category of McIntosh
      active-region classes or any Mount Wilson active-region class gives no
      significant performance improvement over forecasting from the free-energy proxy
      alone (Present MAG4). KEY POINTS: Quantitative comparison of performance of pairs
      of forecasting techniques Next MAG4 forecasts major flares more accurately than
      Present MAG4 Present MAG4 forecast outperforms McIntosh AR Class and total
      magnetic flux.

PMID- 26213518
TI  - Ensemble downscaling in coupled solar wind-magnetosphere modeling for space
      weather forecasting.
AB  - : Advanced forecasting of space weather requires simulation of the whole Sun-to
      Earth system, which necessitates driving magnetospheric models with the outputs
      from solar wind models. This presents a fundamental difficulty, as the
      magnetosphere is sensitive to both large-scale solar wind structures, which can
      be captured by solar wind models, and small-scale solar wind "noise," which is
      far below typical solar wind model resolution and results primarily from
      stochastic processes. Following similar approaches in terrestrial climate
      modeling, we propose statistical "downscaling" of solar wind model results prior
      to their use as input to a magnetospheric model. As magnetospheric response can
      be highly nonlinear, this is preferable to downscaling the results of
      magnetospheric modeling. To demonstrate the benefit of this approach, we first
      approximate solar wind model output by smoothing solar wind observations with an
      8 h filter, then add small-scale structure back in through the addition of random
      noise with the observed spectral characteristics. Here we use a very simple
      parameterization of noise based upon the observed probability distribution
      functions of solar wind parameters, but more sophisticated methods will be
      developed in the future. An ensemble of results from the simple downscaling
      scheme are tested using a model-independent method and shown to add value to the
      magnetospheric forecast, both improving the best estimate and quantifying the
      uncertainty. We suggest a number of features desirable in an operational solar
      wind downscaling scheme. KEY POINTS: Solar wind models must be downscaled in
      order to drive magnetospheric models Ensemble downscaling is more effective than
      deterministic downscaling The magnetosphere responds nonlinearly to small-scale
      solar wind fluctuations.

PMID- 26213519
TI  - Development of the Tongan American Health Professionals Association: Sharing,
      Mentoring and Networking for Community Health.
AB  - INTRODUCTION: Tongan-Americans face severe disparities in health including
      diabetes, cardiovascular disease, and cancer. Educational disparities also affect
      health opportunities and well-being, influencing health status and community
      capacity to address disparities. Few resources have been identified within the
      Tongan-American community to address these concerns. The Tongan American Health
      Professionals Association (TAHPA) was conceived to identify and develop health
      and health career resources for the Tongan community. Through TAHPA, the Tongan
      American community is utilizing a community-empowerment approach to address
      disparities and well-being. METHODS: TAHPA was formed in 2008 through the
      leadership of individuals with a vision of a healthier Tongan-American community.
      TAHPA's purpose was to inspire and empower the Tongan-American community by
      developing an organization of Tongan-American health care professionals and pre
      professionals, celebrating their accomplishments, and providing resources and
      support for educational and career development. Founders gathered in small work
      groups in community settings to discuss health concerns, well-being and
      solutions. Key community members facilitated the process to establish goals and
      objectives. NEXT STEPS: To date, 40 Tongan health professionals and pre
      professionals have become members. TAHPA's vision and outreach processes have
      been developed. TAHPA's uniqueness and strength is that it is rooted in the
      community, created by the community to serve the community.

PMID- 26213520
TI  - Dielectric Spectroscopy of Pressurized Saccharomyces cerevisiae.
AB  - Results of broadband dielectric spectroscopy (BDS) in Saccharomyces cerevisiae
      (baker's yeast), in situ as the function of pressure are presented. They show a
      clear evidence of a threshold to the new pattern of the pressure evolution of the
      static dielectric permittivity and DC electric conductivity already for Pt  ~
      200MPa at T = 5 oC and Pt  ~ 300MPa at T = 25 oC. BDS monitoring versus pressure
      tests up to P = 400MPa revealed particularly notable changes of properties after
      30 minutes of compressing. Finally, the correlation between the amount of the
      spectrophotometric maximum absorbance and the DC electric conductivity was found.
      All these indicate significance of BDS as the tool for testing of pressure
      properties of cells assemblies, model foods etc., in situ under high pressures.

PMID- 26213521
TI  - NMR Studies of Hetero-Association of Caffeine with di-O-Caffeoylquinic Acid
      Isomers in Aqueous Solution.
AB  - Caffeine hetero-association with 3,5-di-O-caffeoylquinic acid, 3,4-di-O
      caffeoylquinic acid and 4,5-di-O-caffeoylquinic acid in aqueous solution has been
      investigated by one-dimensional (1D) and two-dimensional (2D) high resolution 1H
      and 13C NMR spectroscopy. Self-association of the di-O-caffeoylquinic acid
      isomers has been studied as well. Caffeine-di-O-caffeoylquinic acid isomers
      association constants were measured. The value of the association constant of the
      caffeine-di-O-caffeoylquinic acid complexes is compatible with previous studies
      and within the typical range of reported association constants for other caffeine
      polyphenols complexes. Structural features of the three different complexes have
      also been investigated by NMR spectroscopy combined with quantum chemical
      calculations, and the complex conformation is discussed. Our results show that
      stacking interactions drive the formation of the complexes and that multiple
      equilibria are present in the interaction of caffeine with 3,4-di-O
      caffeoylquinic acid and 4,5-di-O-caffeoylquinic acid while the complex with 3,5
      di-O-caffeoylquinic acid seems to be better defined.

PMID- 26213522
TI  - Surface Properties of Aerated Ion-induced Whey Protein Gels.
AB  - Aerated whey protein gels were formed using calcium chloride, magnesium chloride
      or iron (II) chloride induced gelation of pre-denatured protein dispersions. The
      structure of the obtained gel surface depends on the type and concentration of
      added salt. Higher cation concentration produced gels a with higher quadratic
      mean of the surface roughness and maximum roughness height. Aerated gels of
      optimal properties for retaining air bubbles were characterized by similar
      surface roughness. The surface topography is mainly responsible for changes in
      the wettability. The contact angle of the probe liquid sample depends on the
      liquid surface tension components. An approach based on the contact angle
      hysteresis (CAH) is suitable for determining the total value of the apparent
      surface free energy of such materials. An approach based on the components of
      apparent surface free energy (LWAB) only allows the calculation of the dispersion
      component and electron donor parameter of energy in the case of added magnesium
      and iron salt. Wettability, depending on the nature of the surface, can be
      described for the hydrophilic surface by the Wenzel model, and for the
      hydrophobic surface by the Cassie - Baxter model.

PMID- 26213523
TI  - The Evidence in Support of Physicians and Health Care Providers as Physical
      Activity Role Models.
AB  - Physical inactivity constitutes the fourth leading cause of death worldwide.
      Health care providers (HCPs) should play a key role in counseling and
      appropriately referring their patients to adopt physical activity (PA). Previous
      reports suggest that active HCPs are more likely to provide better, more
      credible, and motivating preventive counseling to their patients. This review
      summarizes the available evidence on the association between HCPs' personal PA
      habits and their related PA counseling practices. Based on relevant studies, a
      snowball search strategy identified, out of 196 studies screened, a total of 47
      pertinent articles published between 1979 and 2012. Of those, 23 described HCPs'
      PA habits and/or their counseling practices and 24 analytic studies evaluated the
      association between HCPs' personal PA habits and their PA counseling practices.
      The majority of studies came from the United States (n = 33), and 9 studies
      included nonphysicians (nurses, pharmacists, and other HCPs). PA levels were
      mostly self-reported, and counseling was typically assessed as self-reported
      frequency or perceived self-efficacy in clinical practice. Most (19 out of 24)
      analytic studies reported a significant positive association between HCPs' PA
      habits and counseling frequency, with odds ratios ranging between 1.4 and 5.7 (P
      < .05), in 6 studies allowing direct comparison. This review found consistent
      evidence supporting the notion that physically active physicians and other HCPs
      are more likely to provide PA counseling to their patients and can indeed become
      powerful PA role models. This evidence appears sufficient to justify randomized
      trials to determine if adding interventions to promote PA among HCPs, also
      results in improvements in the frequency and quality of PA preventive counseling
      and referrals, delivered by HCPs, to patients in primary care settings. Future
      studies should also aim at objectively quantifying the effect of HCPs' PA role
      modeling and how it influences patients' PA levels. More evidence from low-to
      middle income countries is needed, where 80% of the deaths due to inactivity and
      related noncommunicable diseases already occur.

PMID- 26213524
TI  - The performance of integrated health care networks in continuity of care: a
      qualitative multiple case study of COPD patients.
AB  - BACKGROUND: Integrated health care networks (IHN) are promoted in numerous
      countries as a response to fragmented care delivery by providing a coordinated
      continuum of services to a defined population. However, evidence on their
      effectiveness and outcome is scarce, particularly considering continuity across
      levels of care; that is the patient's experience of connected and coherent care
      received from professionals of the different care levels over time. The objective
      was to analyse the chronic obstructive pulmonary disease (COPD) patients'
      perceptions of continuity of clinical management and information across care
      levels and continuity of relation in IHN of the public health care system of
      Catalonia. METHODS: A qualitative multiple case study was conducted, where the
      cases are COPD patients. A theoretical sample was selected in two stages: (1)
      study contexts: IHN and (2) study cases consisting of COPD patients. Data were
      collected by means of individual, semi-structured interviews to the patients,
      their general practitioners and pulmonologists and review of records. A thematic
      content analysis segmented by IHN and cases with a triangulation of sources and
      analysists was carried out. RESULTS: COPD patients of all networks perceived that
      continuity of clinical management was existent due to clear distribution of roles
      for COPD care across levels, rapid access to care during exacerbations and
      referrals to secondary care when needed; nevertheless, patients of some networks
      highlighted too long waiting times to non-urgent secondary care. Physicians
      generally agreed with patients, however, also indicated unclear distribution of
      roles, some inadequate referrals and long waiting times to primary care in some
      networks. Concerning continuity of information, patients across networks
      considered that their clinical information was transferred across levels via
      computer and that physicians also used informal communication mechanisms (e-mail,
      telephone); whereas physicians highlighted numerous problems of the information
      system, thus the need to use informal communication channels. Finally, regarding
      continuity of relation, patients of some networks pointed out high turnover of
      personnel - being frequently seen by locum doctors or assigned to new physicians 
      which hindered the development of a trusting relationship. CONCLUSION: Study
      findings suggest a generally perceived adequate performance of IHN in continuity
      of care but also the existence of a series of difficulties related to all
      continuity types. Results can provide opportunities to improving the care process
      of COPD patients but also of patients with other conditions who receive care
      across the primary and secondary care level.

PMID- 26213525
TI  - Biotechnological approaches to enhance salidroside, rosin and its derivatives
      production in selected Rhodiola spp. in vitro cultures.
AB  - Rhodiola (Crassulaceae) an arctic-alpine plant, is extensively used in
      traditional folk medicine in Asian and European countries. A number of
      investigations have demonstrated that Rhodiola preparations exhibit adaptogenic,
      neuroprotective, anti-tumour, cardioprotective, and anti-depressant effects. The
      main compounds responsible for these activities are believed to be salidroside,
      rosin and its derivatives which became the target of biotechnological
      investigations. This review summarizes the results of the diverse
      biotechnological approaches undertaken to enhance the production of salidroside,
      rosin and its derivatives in callus, cell suspension and organ in vitro cultures
      of selected Rhodiola species.

PMID- 26213526
TI  - The role of triterpenes in the management of diabetes mellitus and its
      complications.
AB  - Diabetes mellitus is a chronic metabolic disease which is a serious global
      problem. In 2010 an estimated 285 million people had diabetes and within the next
      20 years this value is expected to almost double. Many antidiabetic therapies
      focus on improving insulin sensitivity, increasing insulin production, and/or
      decreasing the level of blood glucose. Although a number of synthetic medicines
      are available, drugs of natural origin have aroused great interest. Triterpenes
      seem to demonstrate adequate properties. Many experiments have shown that these
      compounds have several antidiabetic mechanisms. They can inhibit enzymes involved
      in glucose metabolism, prevent the development of insulin resistance and
      normalize plasma glucose and insulin levels. These natural compounds, in contrast
      to synthetic drugs, apart from producing a hypoglycemic effect have also been
      found to manifest hypolipidemic and anti-obesity activity. Triterpenes are also
      promising agents in the prevention of diabetic complications. They have strong
      antioxidant activity and inhibit the formation of advanced glycation end
      products, implicated in the pathogenesis of diabetic nephropathy, embryopathy,
      neuropathy or impaired wound healing. Until now very few clinical studies have
      been concerned with the application of triterpenes in treating diabetes. However,
      due to their great therapeutic potential, these compounds deserve special
      attention.

PMID- 26213527
TI  - Benefit-Cost Analysis of a Randomized Evaluation of Communities That Care:
      Monetizing Intervention Effects on the Initiation of Delinquency and Substance
      Use Through Grade 12.
AB  - OBJECTIVE: To determine whether the Communities That Care (CTC) prevention system
      is a cost-beneficial intervention. METHODS: Data were from a longitudinal panel
      of 4,407 youth participating in a randomized controlled trial including 24 towns
      in 7 states, matched in pairs within state and randomly assigned to condition.
      Significant differences favoring intervention youth in sustained abstinence from
      delinquency, alcohol use, and tobacco use through Grade 12 were monetized and
      compared to economic investment in CTC. RESULTS: CTC was estimated to produce
      $4,477 in benefits per youth (discounted 2011 dollars). It cost $556 per youth to
      implement CTC for 5 years. The net present benefit was $3,920. The benefit-cost
      ratio was $8.22 per dollar invested. The internal rate of return was 21%. Risk
      that investment would exceed benefits was minimal. Investment was expected to be
      recouped within 9 years. Sensitivity analyses in which effects were halved
      yielded positive cost-beneficial results. CONCLUSIONS: CTC is a cost-beneficial,
      community-based approach to preventing initiation of delinquency, alcohol use,
      and tobacco use. CTC is estimated to generate economic benefits that exceed
      implementation costs when disseminated with fidelity in communities.

PMID- 26213528
TI  - Accelerometry-based Recognition of the Placement Sites of a Wearable Sensor.
AB  - This work describes an automatic method to recognize the position of an
      accelerometer worn on five different parts of the body: ankle, thigh, hip, arm
      and wrist from raw accelerometer data. Automatic detection of body position of a
      wearable sensor would enable systems that allow users to wear sensors flexibly on
      different body parts or permit systems that need to automatically verify sensor
      placement. The two-stage location detection algorithm works by first detecting
      time periods during which candidates are walking (regardless of where the sensor
      is positioned). Then, assuming that the data refer to walking, the algorithm
      detects the position of the sensor. Algorithms were validated on a dataset that
      is substantially larger than in prior work, using a leave-one-subject-out cross
      validation approach. Correct walking and placement recognition were obtained for
      97.4% and 91.2% of classified data windows, respectively.

PMID- 26213529
TI  - Micropatterning Alginate Substrates for in vitro Cardiovascular Muscle on a Chip.
AB  - Soft hydrogels such as alginate are ideal substrates for building muscle in vitro
      because they have structural and mechanical properties close to the in vivo
      extracellular matrix (ECM) network. However, hydrogels are generally not amenable
      to protein adhesion and patterning. Moreover, muscle structures and their
      underlying ECM are highly anisotropic, and it is imperative that in vitro models
      recapitulate the structural anisotropy in reconstructed tissues for in vivo
      relevance due to the tight coupling between sturcture and function in these
      systems. We present two techniques to create chemical and structural
      heterogeneities within soft alginate substrates and employ them to engineer
      anisotropic muscle monolayers: (i) microcontact printing lines of extracellular
      matrix proteins on flat alginate substrates to guide cellular processes with
      chemical cues, and (ii) micromolding of alginate surface into grooves and ridges
      to guide cellular processes with topographical cues. Neonatal rat ventricular
      myocytes as well as human umbilical artery vascular smooth muscle cells
      successfully attach to both these micropatterned substrates leading to subsequent
      formation of anisotropic striated and smooth muscle tissues. Muscular thin film
      cantilevers cut from these constructs are then employed for functional
      characterization of engineered muscular tissues. Thus, micropatterned alginate is
      an ideal substrate for in vitro models of muscle tissue because it facilitates
      recapitulation of the anisotropic architecture of muscle, mimics the mechanical
      properties of the ECM microenvironment, and is amenable to evaluation of
      functional contractile properties.

PMID- 26213530
TI  - Delivery of iPS-NPCs to the Stroke Cavity within a Hyaluronic Acid Matrix
      Promotes the Differentiation of Transplanted Cells.
AB  - Stroke is the leading cause of adult disability with ~80% being ischemic. Stem
      cell transplantation has been shown to improve functional recovery. However, the
      overall survival and differentiation of these cells is still low. The infarct
      cavity is an ideal location for transplantation as it is directly adjacent to the
      highly plastic peri-infarct region. Direct transplantation of cells near the
      infarct cavity has resulted in low cell viability. Here we deliver neural
      progenitor cells derived from induce pluripotent stem cells (iPS-NPC) to the
      infarct cavity of stroked mice encapsulated in a hyaluronic acid hydrogel matrix
      to protect the cells. To improve the overall viability of transplanted cells,
      each step of the transplantation process was optimized. Hydrogel mechanics and
      cell injection parameters were investigated to determine their effects on the
      inflammatory response of the brain and cell viability, respectively. Using
      parameters that balanced the desire to keep surgery invasiveness minimal and cell
      viability high, iPS-NPCs were transplanted to the stroke cavity of mice
      encapsulated in buffer or the hydrogel. While the hydrogel did not promote stem
      cell survival one week post-transplantation, it did promote differentiation of
      the neural progenitor cells to neuroblasts.

PMID- 26213531
TI  - Room Temperature Ferrimagnetism and Ferroelectricity in Strained, Thin Films of
      BiFe0.5Mn0.5O3.
AB  - Highly strained films of BiFe0.5Mn0.5O3 (BFMO) grown at very low rates by pulsed
      laser deposition were demonstrated to exhibit both ferrimagnetism and
      ferroelectricity at room temperature and above. Magnetisation measurements
      demonstrated ferrimagnetism (TC ~ 600K), with a room temperature saturation
      moment (MS ) of up to 90 emu/cc (~ 0.58 MUB /f.u) on high quality (001) SrTiO3. X
      ray magnetic circular dichroism showed that the ferrimagnetism arose from
      antiferromagnetically coupled Fe3+ and Mn3+. While scanning transmission electron
      microscope studies showed there was no long range ordering of Fe and Mn, the
      magnetic properties were found to be strongly dependent on the strain state in
      the films. The magnetism is explained to arise from one of three possible
      mechanisms with Bi polarization playing a key role. A signature of room
      temperature ferroelectricity in the films was measured by piezoresponse force
      microscopy and was confirmed using angular dark field scanning transmission
      electron microscopy. The demonstration of strain induced, high temperature
      multiferroism is a promising development for future spintronic and memory
      applications at room temperature and above.

PMID- 26213532
TI  - Electrostatically Directed Self-Assembly of Ultrathin Supramolecular Polymer
      Microcapsules.
AB  - Supramolecular self-assembly offers routes to challenging architectures on the
      molecular and macroscopic scale. Coupled with microfluidics it has been used to
      make microcapsules-where a 2D sheet is shaped in 3D, encapsulating the volume
      within. In this paper, a versatile methodology to direct the accumulation of
      capsule-forming components to the droplet interface using electrostatic
      interactions is described. In this approach, charged copolymers are selectively
      partitioned to the microdroplet interface by a complementary charged surfactant
      for subsequent supramolecular cross-linking via cucurbit[8]uril. This dynamic
      assembly process is employed to selectively form both hollow, ultrathin
      microcapsules and solid microparticles from a single solution. The ability to
      dictate the distribution of a mixture of charged copolymers within the
      microdroplet, as demonstrated by the single-step fabrication of distinct core
      shell microcapsules, gives access to a new generation of innovative self
      assembled constructs.

PMID- 26213534
TI  - Food dependant exercise induced anaphylaxis a retrospective study from 2 allergy
      clinics in Colombo, Sri Lanka.
AB  - The aetiology of anaphylaxis ranges from food, insect venom, drugs and various
      chemicals. Some individuals do not develop anaphylaxis with the offending agent
      unless ingestion is related temporally to physical exertion, namely food
      dependent exercise induced anaphylaxis (FDEIA). The foods implicated are wheat,
      soya, peanut, milk and sea food. A retrospective study on patients with FDEIA
      from two Allergy clinics in Sri Lanka from 2011 to 2015 is reported. Patients
      were selected who fulfilled the following criteria: clinical diagnosis of
      anaphylaxis according to the World Allergy Organization (WAO) criteria, where the
      onset of symptoms was during exertion, within 4 h of ingesting a food, the
      ability to eat the implicated food independent of exercise, or exercise safely,
      if the food was not ingested in the preceding 4 h and an in vitro (ImmunoCap
      serum IgE to the food) or in vivo (skin prick test) test indicating evidence of
      sensitivity to the food. There were 19 patients (12 males: 7 females). The ages
      ranged from 9 to 45 (mean 22.9, median 19 years). Eight patients (42.1%) were in
      the 9-16 age group. Those below 16 years had a male:female ratio of 3:5, while
      for those above 16 years it was 9:2. Wheat was the only food implicated in FDEIA
      in all patients and was confirmed by skin prick testing, or by ImmunoCap specific
      IgE to wheat or omega - 5 gliadin. All patients had urticaria, while 5/19 (26.3%)
      had angioedema of the lips. Fifteen patients (78.9%) had shortness of breath or
      wheezing, while 8 (42.1%) had lost consciousness. Nine patients (47. 3%) had
      hypotension. Fourteen (73.6%) of our patients had severe reactions, with loss of
      consciousness or hypotension, while 5 (26.3%) had symptoms related to the
      gastrointestinal tract. One patient developed anaphylaxis on two occasions
      following inhalation of ganja, a local cannabis derivative along with the
      ingestion of wheat and exertion. Wheat is the main food implicated in FDEIA in
      Sri Lanka. A local cannabis derivative, ganja has been implicated as a cofactor
      for the first time. 

PMID- 26213533
TI  - Analytical strategies for studying stem cell metabolism.
AB  - Owing to their capacity for self-renewal and pluripotency, stem cells possess
      untold potential for revolutionizing the field of regenerative medicine through
      the development of novel therapeutic strategies for treating cancer, diabetes,
      cardiovascular and neurodegenerative diseases. Central to developing these
      strategies is improving our understanding of biological mechanisms responsible
      for governing stem cell fate and self-renewal. Increasing attention is being
      given to the significance of metabolism, through the production of energy and
      generation of small molecules, as a critical regulator of stem cell functioning.
      Rapid advances in the field of metabolomics now allow for in-depth profiling of
      stem cells both in vitro and in vivo, providing a systems perspective on key
      metabolic and molecular pathways which influence stem cell biology. Understanding
      the analytical platforms and techniques that are currently used to study stem
      cell metabolomics, as well as how new insights can be derived from this
      knowledge, will accelerate new research in the field and improve future efforts
      to expand our understanding of the interplay between metabolism and stem cell
      biology.

PMID- 26213536
TI  - Alterations of the Danger Zone after Preparation of Curved Root Canals Using
      WaveOne with Reverse Rotation or Reciprocation Movements.
AB  - INTRODUCTION: The aim of this study was to compare the changes that occur in the
      danger zone (DZ) after preparation of curved mesiobuccal (MB) canals of
      mandibular first molars with WaveOne instruments in two different movements
      [reciprocation (RCP) and counter-clockwise rotation (CCWR)] by means of cone-beam
      computed tomography (CBCT). METHODS AND MATERIALS: MB canals of 30 mandibular
      molars were randomly divided into 2 groups (n=15); WaveOne/RCP and WaveOne/CCWR.
      Pre- and post-instrumentation CBCT images were assessed for changes in the dentin
      thickness in DZ (2 and 4 mm below the highest point of the root furcation) in
      both groups. Data was analyzed using the repeated measures ANOVA test. RESULTS:
      There was no statistically significant difference between two experimental groups
      in terms of remaining dentin thickness at 2 and 4 mm levels below the highest
      point of the furcation (P>0.05). CONCLUSION: The efficacy of WaveOne instrument
      on changes of the dentin thickness in the DZ was not affected by different file
      movements.

PMID- 26213535
TI  - Choice of Treatment Plan Based on Root Canal Therapy versus Extraction and
      Implant Placement: A Mini Review.
AB  - Case selection and treatment plan are important aspects of endodontic treatment.
      Dentists should organize the treatment plan based on their knowledge, abilities,
      skills and more importantly the patients' preference and dentition. Indubitably,
      the treatment plan for each patient is exclusive and "tailor-made" and cannot be
      used for all patients. Dentists' selfestimation of their abilities opens up
      treatment options; however, in difficult or complicated cases it is advisable to
      refer to a specialist. Currently, one of the most challenging aspects in
      dentistry is the choice between extraction and placement of implant (EPI) instead
      of a complicated root canal treatment (RCT). Overemphasis on one treatment plan
      while neglecting other options, not only mislead the dentist but also impose
      unnecessary charges to the patients. This mini-review compares RCT to EPI from
      various aspects to help practitioners in routine decision making. 

PMID- 26213537
TI  - Effects of Chlorhexidine and Sodium Hypochlorite on the Setting Time of Calcium
      Enriched Mixture Cement.
AB  - INTRODUCTION: The aim of the present study was to evaluate whether adding 2%
      chlorhexidine (CHX) and 2.6% sodium hypochlorite (NaOCl) to calcium-enriched
      mixture (CEM) cement would affect its setting time (ST), or not. METHODS AND
      MATERIALS: In this study, the setting time of CEM cement was evaluated in three
      groups (n=9) as follows: group 1; CEM cement, group 2; CEM cement+2% CHX and
      group 3; CEM cement+2.6% NaOCl. Then the mean values of ST were calculated and
      the Kolmogorov-Smirnov test was used to evaluate the normal distribution of data.
      The Kruskal-Wallis and Mann-Whitney U tests were used for statistical analysis.
      Statistical significance was set at 0.05. RESULTS: The mean ST for groups 1, 2
      and 3 were 105, 120 and 220 min, respectively. There was a significant increase
      in the duration of ST in group 3 (NaOCl) in comparison with the two other groups
      (P<0.05). CONCLUSION: NaOCl significantly increased the ST of CEM cement, whereas
      chlorhexidine did not alter the ST.

PMID- 26213538
TI  - Apical Extrusion of Debris after Canal Preparation with Hand-Files Used Manually
      or Installed on Reciprocating Air-Driven Handpiece in Straight and Curved Canals.
AB  - INTRODUCTION: Apical debris extrusion (DE) subsequent to root canal
      instrumentation, is one of the most important causes of endodontic flare-ups. The
      aim of this study was to compare the amount of DE after root canal
      instrumentation using nickel-titanium (NiTi) hand files with step-back manual
      technique or installed on reciprocating handpiece. METHODS AND MATERIALS: This
      study was conducted on mesiobuccal (MB) roots of extracted maxillary first molars
      (n=20) and roots of mandibular premolars (n=20) that were randomly divided into
      two groups (n=20) according to the armamentarium used for canal preparation (air
      driven reciprocating handpiece or hand instrumentation). In each group, the MB
      and premolar roots were prepared with the main apical sizes of 35 and 40,
      respectively. The extruded debris were collected and weighed. Finally, the mean
      dry weights were compared using ANOVA and t-test, and Tukey's Multiple
      Comparisons Procedures were used to determine the significant differences in
      amounts of DE. The level of significance was set at 0.05. RESULTS: Regardless of
      the type of teeth, the mean values of DE, were significantly lower in the
      handpiece group (P<0.0001). In addition, significantly lower amounts of DE was
      observed in premolars in similar group (P<0.001). However, this difference was
      not significant in MB roots of molars (P=0.20). CONCLUSION: Root canal
      preparation with reciprocating handpiece can lead to significantly lower debris
      extrusion than the manual step-back technique. In handpiece-prepared canals, the
      amount of extruded debris was significantly lower in premolar teeth.

PMID- 26213539
TI  - The Effect of Preparation Size on Efficacy of Smear Layer Removal; A Scanning
      Electron Microscopic Study.
AB  - INTRODUCTION: Enlargement of the root canal may potentially affect efficient
      smear layer (SL) removal. The aim of the present in vitro study was to compare SL
      removal following canal preparation with two different sizes/tapers by means of
      scanning electron microscopy (SEM). METHODS AND MATERIALS: A total of 50
      extracted human mandibular premolars were decoronated. The teeth were randomly
      divided into two experimental groups (n=20) and two negative control groups. In
      groups 1 and 2 the sizes of master apical file (MAF) were #25 and 40,
      respectively. Coronal part of the canals were flared with #2 Piezo drills in
      group 1 and sizes #2 to 6 in group 2. Finally FlexMaster NiTi rotary instruments
      were used to complete canal preparation (25/0.04 and 35/0.06 in groups 1 and 2,
      respectively). The irrigation protocol consisted of 10 mL of 17%
      ethylenediaminetetraacetic acid (EDTA) for 1 min followed by 10 mL of 5.25% NaOCl
      for 3 min. The patency of dentinal tubules was evaluated under SEM with Hulsmann
      scores. Data were analyzed with the Kruskal-Wallis and Mann-Whitney U tests.
      RESULTS: The number of patent dentinal tubules in coronal third of the group 1
      was significantly more than group 2 (P<0.001). However, this difference was not
      significant for the middle and apical segments. There was a significant
      difference in the number of patent dentinal tubules between coronal, middle and
      apical thirds (P<0.05). CONCLUSION: Increasing the canal preparation size did not
      lead to better cleanliness of the canal walls and more efficient smear layer
      removal.

PMID- 26213540
TI  - The Effect of Smear Layer on Antimicrobial Efficacy of Three Root Canal
      Irrigants.
AB  - INTRODUCTION: One of the main goals of endodontic treatment is to decrease the
      harboring bacteria within the root canal system and dentinal tubules. This
      experimental study attempted to investigate the antibacterial efficacy of three
      root canal irrigants in the presence and absence of smear layer (SL). METHODS AND
      MATERIALS: A total of 210 sound extracted human single-rooted teeth were
      prepared. After creating the SL and its removal in half of the samples, they were
      infected with Candida albicans (C. albicans) and Actinomyces israelii (A.
      israelii). A total of 180 specimen were used to assess the antimicrobial efficacy
      of the three irrigants in presence and absence of SL, 24 specimen were placed in
      the positive and negative controls, 2 samples were utilized for scanning electron
      microscopy (SEM) analysis and 2 were used for Gram staining. Then, they were
      exposed to irrigants including 2.61% sodium hypochlorite (NaOCl), 0.2%
      chlorhexidine gluconate (CHX) and 1% povidone-iodine (PI) for 5, 30 and 60 min.
      Presence/absence of test microorganisms was determined by incubation of specimens
      in test tubes containing brain-heart infusion (BHI) broth and then measuring the
      colony forming units (CFU) on BHI agar. A cumulative logistic model was used to
      analyze the ordinal response. RESULTS: The 2.61% solution of NaOCl was
      significantly more effective than 0.2% CHX and the latter was more efficient than
      1% PI for decreasing fungal and microbial infection of dentinal tubules in the
      presence and absence of SL. CONCLUSION: The presence of smear layer decreased the
      efficacy of antimicrobial irrigants. The minimum time required for elimination of
      fungal/microbial infection was 30 min.

PMID- 26213541
TI  - Antimicrobial Activity of Calcium Hydroxide and Betamethasone on Enterococcus
      faecalis; An in vitro Assessment.
AB  - INTRODUCTION: Calcium hydroxide (CH) is one of the most common intracanal
      medications. Corticosteroids (CS) are used in endodontics because of their anti
      inflammatory activity. This study aimed to evaluate the antimicrobial effect of
      CH+betamethasone and CH+saline against Enterococcus faecalis (E. faecalis) using
      agar diffusion test and measuring the microbial zone of inhibition (ZOI). METHODS
      AND MATERIALS: Four plates containing Mueller-Hinton broth and E. faecalis
      culture media, were prepared. In each plate, 5 holes (5*3 mm) were created and a
      creamy mixture of CH+betamethasone was inserted into the holes (10 holes for each
      material). Two holes with ampicillin disks and two empty holes were used as
      negative and positive controls, respectively. Plates were incubated for 24 h and
      then the diameter of microbial ZOI was measured. The pH of each mixture was
      measured by pH meter. Data were analyzed using the Mann-Whitney U test. RESULTS:
      The mean diameter of ZOI for CH+betamethasone and CH+saline was 3.4 and 3 mm,
      respectively. The difference was not significant (P=0.143). The pH was 12.5 for
      CH+saline and 12.3 CH+betamethasone, respectively. CONCLUSION: The mixture of
      CH+betamethasone had good antimicrobial effects against E. faecalis. Further
      studies are needed to confirm the value of this mixture in clinical settings.

PMID- 26213542
TI  - Immunohistochemical Evaluation of Fibronectin and Tenascin Following Direct Pulp
      Capping with Mineral Trioxide Aggregate, Platelet-Rich Plasma and Propolis in
      Dogs' Teeth.
AB  - INTRODUCTION: The aim of the present study was to evaluate the expression of
      fibronectin (FN) and tenascin (TN) after direct pulp capping (DPC) in dogs' teeth
      with either mineral trioxide aggregate (MTA), Propolis or Platelet-rich plasma
      (PRP), by means of immunohistochemistry. METHODS AND MATERIALS: A total of 48
      sound molars and premolars with mature apices from four dogs, were included. The
      teeth were randomly divided into 4 groups according to the material used for DPC:
      PRP, Propolis, MTA, and glass-ionomer (as the negative control group). Each group
      was divided into two 7-day and 30-day subgroups. The teeth were restored at the
      same session. The animals were sacrificed at the mentioned time intervals and the
      expression of FN and TN in each test group and between each time intervals was
      assessed with Wilcoxon and Mann-Whitney U tests, respectively. The Kruskal-Wallis
      test was used to compare FN and TN staining among the test groups. The
      significance level was set at 0.05. RESULTS: The amount of FN in the MTA group in
      the 30-day interval was significantly higher than the 7-day interval; however,
      there were no significant differences among the other groups. The amount of TN in
      the MTA and Propolis groups in the 30-day interval was significantly higher than
      that in the 7-day interval; no recognizable difference was observed in the other
      groups. Moreover, the difference in expression of FN and TN in the 7-day interval
      was not significant in the experimental groups. Nevertheless, the difference was
      significant in the 30-day interval, with the highest and lowest expressions
      belonging to the MTA and glass-ionomer groups, respectively. CONCLUSION: Based on
      the results of the present animal study, MTA is still a better choice for direct
      pulp capping.

PMID- 26213543
TI  - Effect of Metal Artifacts on Detection of Vertical Root Fractures Using Two Cone
      Beam Computed Tomography Systems.
AB  - INTRODUCTION: Vertical root fracture (VRF) is common in endodontically treated
      teeth. Conventional and digital radiographies have limitations for detection of
      VRFs. Cone-beam computed tomography (CBCT) offers greater detection accuracy of
      VRFs in comparison with conventional radiography. This study compared the effects
      of metal artifacts on detection of VRFs by using two CBCT systems. METHODS AND
      MATERIALS: Eighty extracted premolars were selected and sectioned at the level of
      the cemento enamel junction (CEJ). After preparation, root canals were filled
      with gutta-percha. Subsequently, two thirds of the root fillings were removed for
      post space preparation and a custom-made post was cemented into each canal. The
      teeth were randomly divided into two groups (n=40). In the test group, root
      fracture was created with Instron universal testing machine. The control teeth
      remained intact. CBCT scans of all teeth were obtained with either New Tom VGI or
      Soredex Scanora 3D. Three observers analyzed the images for detection of VRF. The
      sensitivity, specificity, positive predictive value (PPV) and negative predictive
      value (NPV) for VRF detection and percentage of probable cases were calculated
      for each imaging system and compared using non-parametric tests considering the
      non-normal distribution of data. The inter-observer reproducibility was
      calculated using the weighted kappa coefficient. RESULTS: There were no
      statistically significant differences in sensitivity, specificity, PPV and NPV
      between the two CBCT systems. CONCLUSION: The effect of metal artifacts on VRF
      detection was not significantly different between the two CBCT systems.

PMID- 26213545
TI  - Treatment of Dens Invagination in a Maxillary Lateral Incisor: A Case Report.
AB  - Dens invagination is a developmental anomaly requiring specific treatment
      approaches. Oehler's Type III dens in dente, extends into the root and perforates
      at the apical area or lateral surface of the root. In this case endodontic
      treatment of the invaginated tooth was carried out through the central lumen of
      the invagination with calcium hydroxide without manipulation of the main pulp
      canal, thereby leaving the tooth vital. The 18-month follow-up examinations were
      indicative of treatment success; the periapical lesion resolved completely and
      the tooth remained vital. CONCLUSION: Information about the three dimensional
      anatomy of the teeth especially those with an abnormality is necessary for a
      successful treatment.

PMID- 26213544
TI  - Microleakage of Single-Cone Gutta-Percha Obturation Technique in Combination with
      Different Types of Sealers.
AB  - INTRODUCTION: Various materials and methods have been recommended for successful
      root canal obturation. The aim of this experimental in vitro study was to compare
      the sealing ability of three root canal sealers AH-26, glass ionomer cement (GIC)
      and zinc oxide eugenol (ZOE) in single gutta-percha obturating system. METHODS
      AND MATERIALS: Seventy extracted single-rooted human teeth were decoronated. The
      teeth were randomly divided into 3 experimental groups (n=20) and 2 positive and
      negative control groups. After root canal preparation, canals were obturated with
      single-cone method using either AH-26, GIC and ZOE. The leakage was evaluated
      using the dye penetration method. The samples were sectioned to evaluate the
      linear leakage using a stereomicroscope. The data were analyzed using the One-way
      ANOVA test. RESULTS: All the specimens in the positive control group showed
      evidence of leakage. In the experimental groups, the lowest leakage scores were
      observed in the AH-26 group (P<0.05). However, there were no statistically
      significant differences between GIC and ZOE samples (P=0.676). CONCLUSION: AH-26
      showed a superior seal and less microleakage compared to the two other materials
      in single gutta-percha obturating system.

PMID- 26213546
TI  - A Successful Endodontic Outcome with Non-Obturated Canals.
AB  - This case report represents the outcome of endodontic treatment in an infected
      mandibular molar with periradicular periodontitis and inherent poor prognosis of
      root canal treatment due to severe root curvature. The tooth was successfully
      treated by leaving the mesial root non-obturated, the canal orifices were
      coronally sealed with calcium enriched mixture cement and a definitive coronal
      amalgam restoration, was placed at the subsequent visit. 

PMID- 26213547
TI  - Haploidentical hematopoietic stem cell transplantation in children and
      adolescents with acquired severe aplastic anemia.
AB  - Severe aplastic anemia (SAA) is a life-threatening disorder for which allogeneic
      hematopoietic stem cell transplantation (HSCT) is the current available curative
      treatment. HSCT from matched sibling donors (MSDs) is the preferred therapy for
      children with acquired SAA. For patients who lack MSDs, immunosuppressive therapy
      (IST) is widely accepted as a first-line treatment before considering HCT from an
      unrelated donor (URD). Given the recent progress in HSCT using URDs for childhood
      SAA, well-matched URDs became a realistic alternative for pediatric patients who
      have no suitable related donors and who are refractory to IST. However, it is
      quite challenging to treat patients with refractory SAA who lack suitable related
      or URDs. Even though haploidentical HSCT from genetically mismatched family
      members seemed to be an attractive procedure with the amazing benefit of readily
      available donors for most patients, early attempts were disappointing because of
      refractory graft-versus-host disease (GVHD) and excessively high transplant
      related mortality. Recent advances with effective ex vivo depletion of T cells or
      unmanipulated in vivo regulation of T cells, better supportive care, and optimal
      conditioning regimens have significantly improved the outcome of haploidentical
      transplant. Besides considerable progress in the treatment of malignant diseases,
      recent emerging evidences for haploidentical HSCT in SAA has provided additional
      therapeutic options for patients with refractory diseases. Further improvements
      to decrease the rates of graft failure, GVHD, and infectious complications will
      facilitate the emergence of haploidentical HSCT as a front-line therapy for
      treating acquired SAA in children and adolescents who have no suitably matched
      donors. 

PMID- 26213548
TI  - Initial steroid regimen in idiopathic nephrotic syndrome can be shortened based
      on duration to first remission.
AB  - PURPOSE: The use of a 12-week steroid regimen (long-term therapy, LT) for the
      first episode of idiopathic nephrotic syndrome (NS) reportedly induces a more
      sustained remission and lower relapse rate than previous regimens, including an 8
      week steroid regimen (short-term therapy, ST). Here, we assessed the potential
      for selective application of 2 steroid regimens (LT vs. ST) based on the days to
      remission (early responders [ER] vs. late responders [LR]) for the first
      idiopathic NS episode in children. METHODS: Patients were divided into 4
      subgroups (ST+ER, ST+LR, LT+ER, and LT+LR) according to the initial steroid
      regimen used and rapidity of response; the baseline characteristics, relapse
      rates, and cumulative percentage of children with sustained remission were then
      compared among the 4 subgroups. RESULTS: Fifty-four children received ST, and the
      remaining 45 children received LT. As observed in previous studies, children
      receiving LT showed significantly lower relapse rates during the first year after
      the first NS episode than those receiving ST. The ST+ER group showed
      significantly lower relapse rates during the first one year and two years after
      the first NS episode than the the ST+LR group, whereas there were no significant
      differences of the relapse rates and duration to the first relapse between the
      ST+ER and LT+ER groups. CONCLUSION: We suggest that the initial steroid regimen
      in idiopathic NS patients can be shortened according to the duration to remission
      i.e., LT in patients achieving remission after the first week of steroid therapy,
      and ST in those achieving remission within the first week of steroid therapy.

PMID- 26213549
TI  - Hepatitis associated with Mycoplasma pneumoniae infection in Korean children: a
      prospective study.
AB  - PURPOSE: Mycoplasma pneumoniae (MP) infection is a major cause of respiratory
      infection in school-aged children. Extrapulmonary manifestations of MP infection
      are common, but liver involvement has been rarely reported. The aim of this study
      was to determine the clinical characteristics of MP-associated hepatitis.
      METHODS: This prospective study included 1,044 pediatric patients with MP
      infection diagnosed serologically with MP IgM at one medical center from January
      2006 to December 2012. Eighty of these patients had elevated levels of serum
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT), each greater
      than 50 IU/L, without any other specific liver disorder and were compared with
      the 964 children without liver disorders. RESULTS: In total, 7.7% of patients
      with MP infection had a diagnosis of hepatitis, especially in fall and winter.
      The ratio of male to female patients was 1.7:1, and the mean age of the patients
      was 5 years and 5 months. The most common symptoms were cough, fever, and sputum.
      Anorexia was the most common gastrointestinal symptom, followed by
      nausea/vomiting, diarrhea, and abdominal pain. Mean levels of AST and ALT were
      100.65 IU/L and 118.73 IU/L, respectively. Serum AST/ALT level was normalized
      within 7.5 days on average without complications. The mean duration of
      hospitalization (11.3 days) was longer for children with hepatitis than for those
      without hepatitis (P=0.034). CONCLUSION: MP-associated hepatitis is not uncommon
      and has a relatively good prognosis. Therefore, clinicians should be concerned
      about liver involvement in MP infection but avoid further unnecessary evaluation
      of hepatitis associated with MP.

PMID- 26213550
TI  - Cardiopulmonary function and scoliosis severity in idiopathic scoliosis children.
AB  - PURPOSE: Idiopathic scoliosis is a structural lateral curvature of the spine of
      unknown etiology. The relationship between degree of spine curvature and
      cardiopulmonary function has not yet been investigated. The purpose of this study
      was to determine the association between scoliosis and cardiopulmonary
      characteristics. METHODS: Ninety children who underwent preoperative pulmonary or
      cardiac evaluation at a single spine institution over 41 months were included.
      They were divided into the thoracic-dominant scoliosis (group A, n=78) and lumbar
      dominant scoliosis (group B, n=12) groups. Scoliosis severity was evaluated using
      the Cobb method. In each group, relationships between Cobb angles and
      cardiopulmonary markers such as forced vital capacity (FVC), forced expiratory
      volume in one second (FEV1), FEV1/FVC, left ventricular ejection fraction,
      pulmonary artery flow velocity, and tissue Doppler velocities (E/E', E'/A') were
      analyzed by correlation analysis linear regression. RESULTS: In group A, 72
      patients (92.3%) underwent pulmonary function tests (PFTs), and 41 (52.6%)
      underwent echocardiography. In group B, 9 patients (75.0%) underwent PFT and 8
      (66.7%) underwent echocardiography. Cobb angles showed a significant negative
      correlation with FVC and FEV1 in group A (both P<0.05), but no such correlation
      in group B, and a significant negative correlation with mitral E/A ratio (P<0.05)
      and tissue Doppler E'/A' (P<0.05) in group A, with a positive correlation with
      mitral E/A ratio (P<0.05) in group B. CONCLUSION: Pulmonary and cardiac function
      was significantly correlated with the degree of scoliosis in patients with
      thoracic-dominant scoliosis. Myocardial diastolic function might be impaired in
      patients with the most severe scoliosis.

PMID- 26213551
TI  - Thyroid dysfunction in very low birth weight preterm infants.
AB  - PURPOSE: Thyroid dysfunction is common in preterm infants. Congenital
      hypothyroidism causes neurodevelopmental impairment, which is preventable if
      properly treated. This study was conducted to describe the characteristics of
      thyroid dysfunction in very low birth weight infants (VLBWIs), evaluate risk
      factors of hypothyroidism, and suggest the reassessment of thyroid function with
      an initially normal thyroid-stimulating hormone (TSH) as part of a newborn
      screening test. METHODS: VLBWIs (January 2010 to December 2012) were divided into
      two groups according to dysfunction-specific thyroid hormone replacement therapy,
      and associated factors were evaluated. RESULTS: Of VLBWIs, 246 survivors were
      enrolled. Only 12.2% (30/246) of enrolled subjects exhibited thyroid dysfunction
      requiring thyroid hormone replacement. Moreover, only one out of 30 subjects who
      required thyroid hormone treatment had abnormal thyroid function in the newborn
      screening test with measured TSH. Most of the subjects in the treatment group
      (22/30) exhibited delayed TSH elevation. Gestational age, Apgar score, antenatal
      steroids therapy, respiratory distress syndrome, patent ductus arteriosus,
      sepsis, intraventricular hemorrhage, postnatal steroids therapy, and duration of
      mechanical ventilation did not differ between the two groups. Birth weight was
      smaller and infants with small for gestational age were more frequent in the
      treatment group. CONCLUSION: Physicians should not rule out suggested
      hypothyroidism, even when thyroid function of a newborn screening test is normal.
      We suggest retesting TSH and free thyroxine in high risk preterm infants with an
      initially normal TSH level using a newborn screening test.

PMID- 26213552
TI  - A novel association between cerebral sinovenous thrombosis and nonketotic
      hyperglycinemia in a neonate.
AB  - Lethargy in newborns usually indicates central nervous system dysfunction, and
      many conditions such as cerebrovascular events, infections, and metabolic
      diseases should be considered in the differential diagnosis. Nonketotic
      hyperglycinemia is an autosomal recessive error of glycine metabolism,
      characterized by myoclonic jerks, hypotonia, hiccups, apnea, and progressive
      lethargy that may progress to encephalopathy or even death. Cerebral sinovenous
      thrombosis is a rare condition with various clinical presentations such as
      seizures, cerebral edema, lethargy, and encephalopathy. Here, we report the case
      of a newborn infant who presented with progressive lethargy. An initial diagnosis
      of cerebral venous sinus thrombosis was followed by confirmation of the presence
      of nonketotic hyperglycinemia. 

PMID- 26213553
TI  - Hepatic glycogenosis in type 1 diabetes mellitus mimicking Mauriac syndrome.
AB  - Hepatic glycogenosis in type 1 diabetes mellitus (DM) can be caused by poor
      glycemic control due to insulin deficiency, excessive insulin treatment for
      diabetic ketoacidosis, or excessive glucose administration to control
      hypoglycemia. Mauriac syndrome, which is characterized by hepatomegaly due to
      hepatic glycogenosis, growth retardation, delayed puberty, and Cushingoid
      features, is a rare diabetic complication. We report a case of hepatic
      glycogenosis mimicking Mauriac syndrome. A 14-year-old girl with poorly
      controlled type 1 DM was admitted to The Catholic University of Korea, Seoul St.
      Mary's Hospital for abdominal pain and distension. Physical examination revealed
      hepatomegaly and a Cushingoid face. The growth rate of the patient had decreased,
      and she had not yet experienced menarche. Laboratory findings revealed elevated
      liver enzyme levels. A liver biopsy confirmed hepatic glycogenosis. Continuous
      glucose monitoring showed hyperglycemia after meals and frequent hypoglycemia
      before meals. To control hyperglycemia, we increased insulin dosage by using an
      insulin pump. In addition, we prescribed uncooked cornstarch to prevent
      hypoglycemia. After strict blood glucose control, the patient's liver functions
      and size normalized. The patient subsequently underwent menarche. Hepatic
      glycogenosis is a complication of type 1 DM that is reversible with appropriate
      glycemic control. 

PMID- 26213554
TI  - Erratum: Validity of bag urine culture for predicting urinary tract infections in
      febrile infants: a paired comparison of urine collection methods.
AB  - [This corrects the article on p. 183 in vol. 58, PMID: 26124849.]. 

PMID- 26213555
TI  - A review of current treatment strategies for gestational diabetes mellitus.
AB  - Approximately 90% of diabetes cases in pregnant women are considered gestational
      diabetes mellitus (GDM). It is well known that uncontrolled glucose results in
      poor pregnancy outcomes in both the mother and fetus. Worldwide there are many
      guidelines with recommendations for appropriate management strategies for GDM
      once lifestyle modifications have been instituted and failed to achieve control.
      The efficacy and particularly the safety of other treatment modalities for GDM
      has been the source of much debate in recent years. Studies that have
      demonstrated the safety and efficacy of both glyburide and metformin in the
      management of patients with GDM will be reviewed. There is a lack of evidence
      with other oral and injectable non-insulin agents to control blood glucose in
      GDM. The role of insulin will be discussed, with emphasis on insulin analogs.
      Ideal patient characteristics for each treatment modality will be reviewed. In
      addition, recommendations for postpartum screening of patients will be described
      as well as recommendations for use of agents to manage subsequent type 2 diabetes
      in patients who are breastfeeding. 

PMID- 26213557
TI  - Transcriptional profiling of predator-induced phenotypic plasticity in Daphnia
      pulex.
AB  - BACKGROUND: Predator-induced defences are a prominent example of phenotypic
      plasticity found from single-celled organisms to vertebrates. The water flea
      Daphnia pulex is a very convenient ecological genomic model for studying predator
      induced defences as it exhibits substantial morphological changes under predation
      risk. Most importantly, however, genetically identical clones can be
      transcriptionally profiled under both control and predation risk conditions and
      be compared due to the availability of the sequenced reference genome. Earlier
      gene expression analyses of candidate genes as well as a tiled genomic microarray
      expression experiment have provided insights into some genes involved in predator
      induced phenotypic plasticity. Here we performed the first RNA-Seq analysis to
      identify genes that were differentially expressed in defended vs. undefended D.
      pulex specimens in order to explore the genetic mechanisms underlying predator
      induced defences at a qualitatively novel level. RESULTS: We report 230
      differentially expressed genes (158 up- and 72 down-regulated) identified in at
      least two of three different assembly approaches. Several of the differentially
      regulated genes belong to families of paralogous genes. The most prominent
      classes amongst the up-regulated genes include cuticle genes, zinc
      metalloproteinases and vitellogenin genes. Furthermore, several genes from this
      group code for proteins recruited in chromatin-reorganization or regulation of
      the cell cycle (cyclins). Down-regulated gene classes include C-type lectins,
      proteins involved in lipogenesis, and other families, some of which encode
      proteins with no known molecular function. CONCLUSIONS: The RNA-Seq transcriptome
      data presented in this study provide important insights into gene regulatory
      patterns underlying predator-induced defences. In particular, we characterized
      different effector genes and gene families found to be regulated in Daphnia in
      response to the presence of an invertebrate predator. These effector genes are
      mostly in agreement with expectations based on observed phenotypic changes
      including morphological alterations, i.e., expression of proteins involved in
      formation of protective structures and in cuticle strengthening, as well as
      proteins required for resource re-allocation. Our findings identify key genetic
      pathways associated with anti-predator defences.

PMID- 26213556
TI  - A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and
      beyond.
AB  - The prevalence of type 2 diabetes is increasing at an astounding rate. Many of
      the agents used to treat type 2 diabetes have undesirable adverse effects of
      hypoglycemia and weight gain. Glucagon-like peptide-1 (GLP-1) receptor agonists
      represent a unique approach to the treatment of diabetes, with benefits extending
      outside glucose control, including positive effects on weight, blood pressure,
      cholesterol levels, and beta-cell function. They mimic the effects of the
      incretin hormone GLP-1, which is released from the intestine in response to food
      intake. Their effects include increasing insulin secretion, decreasing glucagon
      release, increasing satiety, and slowing gastric emptying. There are currently
      four approved GLP-1 receptor agonists in the United States: exenatide,
      liraglutide, albiglutide, and dulaglutide. A fifth agent, lixisenatide, is
      available in Europe. There are important pharmacodynamic, pharmacokinetic, and
      clinical differences of each agent. The most common adverse effects seen with GLP
      1 therapy include nausea, vomiting, and injection-site reactions. Other warnings
      and precautions include pancreatitis and thyroid cell carcinomas. GLP-1 receptor
      agonists are an innovative and effective option to improve blood glucose control,
      with other potential benefits of preserving beta-cell function, weight loss, and
      increasing insulin sensitivity. Once-weekly formulations may also improve patient
      adherence. Overall, these are effective agents for patients with type 2 diabetes,
      who are either uncontrolled on metformin or intolerant to metformin. 

PMID- 26213558
TI  - New models for prediction of micronuclei formation in nuclear medicine department
      workers.
AB  - BACKGROUND: Ionizing radiation causes detrimental health effects such as cancer
      and genetic damage. The study aim was to determine predictors for micronuclei
      (MN) occurrence and frequency in peripheral blood lymphocytes of health workers
      professionally exposed to radiation. METHODS: Health workers, age matched,
      selected for the study on regular check-ups, were divided according to the
      radiation exposure. The exposed group involved nuclear medicine department
      employees (54) and the control group comprised workers from other departments
      (36). Data about workers characteristics and habits, received annual doses (AD),
      total years of service (TYS) and exposed years of service (EYS) were taken from
      each subject. Blood samples were taken and micronuclei (MN) number in peripheral
      blood lymphocytes was calculated using CBMN assay according to standard
      protocols. RESULTS: Most workers were female, technicians, with mean age of 45.67
      years and EYS about 15 years. Health workers exposed to radiation had
      significantly more MN than controls (p = 0.001). Female gender, older age, higher
      received annual doses, longer EYS and TYS increased the MN number. Technicians
      and laboratory workers have higher risk for MN occurrence. Significant predictors
      of MN formation according to constructed model were workers age, sex, AD and EYS.
      One EYS year increases MN frequency 1.017 times, while receiving 0.1 mSy raises
      MN frequency by 26 %. EYS accurately predicts 86.30 % of MN frequencies and AD
      64.60 %. CONCLUSIONS: The model, developed for the first time in this study,
      showed that received annual doses and duration of exposure to radiation can be
      used for prediction of MN numbers.

PMID- 26213559
TI  - Therapeutics for postexposure treatment of Ebola virus infection.
AB  - The current Ebola virus disease (EVD) outbreak in West Africa is the largest with
      over 5100 deaths in four West African countries as of 14 November 2014. EVD has
      high case-fatality rates but no licensed treatment or vaccine is yet available.
      Several vaccine candidates that protected nonhuman primates are not yet available
      for clinical use. Slow development of vaccine-stimulated immunity, sporadic
      nature and fast progression of EVD underlines the need for the development of
      effective postexposure therapeutic drugs. WHO encouraged the use of untested
      drugs for EVD to curb the fast-spreading outbreak. Here, we summarize
      therapeutics for EVD including monoclonal antibody-based therapy and inhibitors
      of viral replication including our recently developed small-molecule inhibitors
      of VP30 dephosphorylation.

PMID- 26213486
TI  - Constraints on the pMSSM, AMSB model and on other models from the search for long
      lived charged particles in proton-proton collisions at [Formula: see text].
AB  - Stringent limits are set on the long-lived lepton-like sector of the
      phenomenological minimal supersymmetric standard model (pMSSM) and the anomaly
      mediated supersymmetry breaking (AMSB) model. The limits are derived from the
      results presented in a recent search for long-lived charged particles in proton
      proton collisions, based on data collected by the CMS detector at a centre-of
      mass energy of 8 TeV at the Large Hadron Collider. In the pMSSM parameter sub
      space considered, 95.9 % of the points predicting charginos with a lifetime of at
      least 10 ns are excluded. These constraints on the pMSSM are the first obtained
      at the LHC. Charginos with a lifetime greater than 100 ns and masses up to about
      800 GeV in the AMSB model are also excluded. The method described can also be
      used to set constraints on other models.

PMID- 26213561
TI  - HSV-I and the cellular DNA damage response.
AB  - Peter Wildy first observed genetic recombination between strains of HSV in 1955.
      At the time, knowledge of DNA repair mechanisms was limited, and it has only been
      in the last decade that particular DNA damage response (DDR) pathways have been
      examined in the context of viral infections. One of the first reports addressing
      the interaction between a cellular DDR protein and HSV-1 was the observation by
      Lees-Miller et al. that DNA-dependent protein kinase catalytic subunit levels
      were depleted in an ICP0-dependent manner during Herpes simplex virus 1
      infection. Since then, there have been numerous reports describing the
      interactions between HSV infection and cellular DDR pathways. Due to space
      limitations, this review will focus predominantly on the most recent observations
      regarding how HSV navigates a potentially hostile environment to replicate its
      genome.

PMID- 26213560
TI  - A mechanistic overview of dendritic cell-mediated HIV-1 trans infection: the
      story so far.
AB  - Despite progress in antiretroviral therapy, HIV-1 rebound after cessation of
      antiretroviral therapy suggests that establishment of long-term cellular
      reservoirs of virus is a significant barrier to functional cure. There is
      considerable evidence that dendritic cells (DCs) play an important role in
      systemic virus dissemination. Although productive infection of DCs is
      inefficient, DCs capture HIV-1 and transfer-captured particles to CD4+ T cells, a
      mechanism of DC-mediated HIV-1 trans infection. Recent findings suggest that DC
      mediated trans infection of HIV-1 is dependent on recognition of GM3, a virus
      particle-associated host-derived ligand, by CD169 expressed on DCs. In this
      review, we describe mechanisms of DC-mediated HIV-1 trans infection and discuss
      specifically the role of CD169 in establishing infection in CD4+ T cells.

PMID- 26213562
TI  - Neurons versus herpes simplex virus: the innate immune interactions that
      contribute to a host-pathogen standoff.
AB  - Herpes simplex virus (HSV) is a prevalent neurotropic virus, which establishes
      lifelong latent infections in the neurons of sensory ganglia. Despite our long
      standing knowledge that HSV predominately infects sensory neurons during its life
      cycle, little is known about the neuronal antiviral response to HSV infection.
      Recent studies show that while sensory neurons have impaired intrinsic immunity
      to HSV infection, paracrine IFN signaling can potentiate a potent antiviral
      response. Additionally, antiviral autophagy plays an important role in neuronal
      control of HSV infection. Here we review the literature of antiviral signaling
      and autophagy in neurons, the mechanisms by which HSV can counteract these
      responses, and postulate how these two pathways may synergize to mediate neuronal
      control of HSV infection and yet result in lifelong persistence of the virus.

PMID- 26213568
TI  - An Emerging Role for Angiogenesis in Tendinopathy.

PMID- 26213567
TI  - Lipase-catalyzed biodiesel production and quality with Jatropha curcas oil:
      exploring its potential for Central America.
AB  - BACKGROUND: Extensive native Jatropha curcas L. (Jatropha) crop areas have been
      planted in Central America marginal lands since 2008 as a non-edible prospective
      feedstock alternative to high-value, edible palm oil. Jatropha biodiesel is
      currently exclusively produced in the region at commercial scale utilizing
      alkaline catalysts. Recently, a free, soluble Thermomyces lanuginosus (TL) 1,3
      specific lipase has shown promise as biocatalyst, reportedly yielding up to 96 %
      ASTM D6751 compliant biodiesel after 24 h transesterification of soybean, canola
      oils and other feedstocks. Biodiesel conversion rate and quality of enzymatically
      catalyzed transesterification of Jatropha oil was evaluated. Two lipases: free,
      soluble TL and immobilized Candida antarctica (CA) catalyzed methanolic
      transesterification of crude Jatropha and refined palm oil. RESULTS: Jatropha
      yields were similar to palm biodiesel with NaOH as catalyst. After 24 h
      transesterification, Jatropha (81 %) and palm oil (86 %) biodiesel yields with TL
      as catalyst were significantly higher than CA (<70 %) but inferior to NaOH (>90
      %). Enzymatic catalysts (TL and CA) produced Jatropha biodiesel with optimum flow
      properties but did not complied with ASTM D6751 stability parameters (free fatty
      acid content and oil stability index). CONCLUSIONS: Biodiesel production with
      filtered, degummed, low FFA Jatropha oil using a free liquid lipase (TL) as
      catalyst showed higher yielding potential than immobilized CA lipase as
      substitute of RBD palm oil with alkaline catalyst. However, Jatropha enzymatic
      biodiesel yield and stability were inferior to alkaline catalyzed biodiesel and
      not in compliance with international quality standards. Lower quality due to
      incomplete alcoholysis and esterification, potential added costs due to need of
      more than 24 h to achieve comparable biodiesel yields and extra post
      transesterification refining reactions are among the remaining drawbacks for the
      environmentally friendlier enzymatic catalysis of crude Jatropha oil to become an
      economically viable alternative to chemical catalysis.

PMID- 26213564
TI  - Prediction of mortality in patients with colorectal perforation based on
      routinely available parameters: a retrospective study.
AB  - INTRODUCTION: Even after surgery and intensive postoperative management, the
      mortality rate associated with colorectal perforation is high. Identification of
      mortality markers using routinely available preoperative parameters is important.
      METHODS: We enrolled consecutive patients with colorectal perforation who
      underwent operations from January 2010 to January 2015. We divided them into a
      mortality and survivor group and compared clinical characteristics between the
      two groups. Additionally, we compared the mortality rate between different
      etiologies: malignant versus benign and diverticular versus nondiverticular. We
      used the chi (2) and Mann-Whitney U tests and a logistic regression model to
      identify factors associated with mortality. RESULTS: We enrolled 108 patients,
      and 52 (48 %) were male. The mean age at surgery was 71 +/- 13 years. The
      postoperative mortality rate was 12 % (13 patients). Multivariate logistic
      regression analysis showed that a high patient age (odds ratio [OR], 1.09; 95 %
      confidence interval [CI], 1.020-1.181) and low preoperative systolic blood
      pressure (OR, 0.98; 95 % CI, 0.953-0.999) were independent risk factors for
      mortality in patients with colorectal perforation. In the subgroup analysis,
      there was no significant difference between the malignant and benign group (11.8
      % vs. 23.9 %, respectively; p = 0.970), while the diverticular group had a
      significantly lower mortality rate than the nondiverticular group (2.6 % vs. 17.1
      %, respectively; p = 0.027). CONCLUSIONS: Older patients and patients with low
      preoperative blood pressure had a high risk of mortality associated with
      colorectal perforation. For such patients, operations and postoperative
      management should be performed carefully.

PMID- 26213563
TI  - Downregulating viral gene expression: codon usage bias manipulation for the
      generation of novel influenza A virus vaccines.
AB  - Vaccination represents the best option to protect humans against influenza virus.
      However, improving the effectiveness of current vaccines could better stifle the
      health burden caused by viral infection. Protein synthesis from individual genes
      can be downregulated by synthetically deoptimizing a gene's codon usage. With
      more rapid and affordable nucleotide synthesis, generating viruses that contain
      genes with deoptimized codons is now feasible. Attenuated, vaccine-candidate
      viruses can thus be engineered with hitherto uncharacterized properties. With
      eight gene segments, influenza A viruses with variably recoded genomes can
      produce a spectrum of attenuation that is contingent on the gene segment targeted
      and the number of codon changes. This review summarizes different targets and
      approaches to deoptimize influenza A virus codons for novel vaccine generation.

PMID- 26213569
TI  - Visualization of Miscanthus * giganteus cell wall deconstruction subjected to
      dilute acid pretreatment for enhanced enzymatic digestibility.
AB  - BACKGROUND: The natural recalcitrance of lignocellulosic plant cell walls
      resulting from complex arrangement and distribution of heterogeneous components
      impedes deconstruction of such cell walls. Dilute acid pretreatment (DAP) is an
      attractive method to overcome the recalcitrant barriers for rendering enzymatic
      conversion of polysaccharides. In this study, the internodes of Miscanthus *
      giganteus, a model bioenergy crop, were subjected to DAP to yield a range of
      samples with altered cell wall structure and chemistry. The consequent
      morphological and compositional changes and their possible impact on
      saccharification efficiency were comprehensively investigated. The use of a
      series of microscopic and microspectroscopic techniques including fluorescence
      microscopy (FM), transmission electron microscopy (TEM) and confocal Raman
      microscopy (CRM)) enabled correlative cell wall structural and chemical
      information to be obtained. RESULTS: DAP of M. * giganteus resulted in
      solubilization of arabinoxylan and cross-linking hydroxycinnamic acids in a
      temperature-dependent manner. The optimized pretreatment (1% H2SO4, 170 degrees C
      for 30 min) resulted in significant enhancement in the saccharification
      efficiency (51.20%) of treated samples in 72 h, which amounted to 4.4-fold
      increase in sugar yield over untreated samples (11.80%). The remarkable
      improvement could be correlated to a sequence of changes occurring in plant cell
      walls due to their pretreatment-induced deconstruction, namely, loss in the
      matrix between neighboring cell walls, selective removal of hemicelluloses,
      redistribution of phenolic polymers and increased exposure of cellulose. The
      consequently occurred changes in inner cell wall structure including damaging,
      increase of porosity and loss of mechanical resistance were also found to enhance
      enzyme access to cellulose and further sugar yield. CONCLUSIONS: DAP is a highly
      effective process for improving bioconversion of cellulose to glucose by breaking
      down the rigidity and resistance of cell walls. The combination of the most
      relevant microscopic and microanalytical techniques employed in this work
      provided information crucial for evaluating the influence of anatomical and
      compositional changes on enhanced enzymatic digestibility.

PMID- 26213566
TI  - Crude triterpenoid saponins from Anemone flaccida (Di Wu) exert anti-arthritic
      effects on type II collagen-induced arthritis in rats.
AB  - BACKGROUND: Anemone flaccida Fr . Schmidt (Ranunculaceae) (Di Wu in Chinese) is
      used to treat punch injury and rheumatoid arthritis (RA). However, the active
      compounds and underlying mechanism of action mediating the anti-arthritic effects
      of A. flaccida remain unclear. This study aims to evaluate the underlying action
      mechanism of A. flaccida crude triterpenoid saponins (AFS) on RA using a type II
      collagen (CII)-induced arthritis (CIA) rat model, and to assess the anti
      inflammatory effects of the main active compounds of AFS, namely flaccidoside II,
      anhuienoside E, glycoside St-I4a, hemsgiganoside B, hederasaponin B, and 3-O
      alpha-l-rhamnopyranosyl (1 -> 2)-beta-d-glucopyranosyl oleanolic acid 28-O-beta-d
      glucopyranosyl (1 -> 6)-beta-d-glucopyranosyl ester. METHODS: Male Wistar rats (n
      = 50) were randomly separated into five groups (n = 10) and immunized by CII
      injection. AFS (200 or 400 mg/kg) and dexamethasone were orally administered for
      30 days after establishing the model. The arthritis severity was assessed by paw
      volume using a plethysmometer. After 30 days of treatment, the right hind paws of
      the rats were obtained. Paw histology was analyzed by hematoxylin and eosin
      staining, and radiologic imaging was performed by micro-computed tomography. MTT
      assays were used to evaluate the cytotoxicity of AFS and its main compounds in
      RAW264.7 cells. Enzyme-linked immunosorbent assay kits were used to measure
      interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in serum and
      supernatants from AFS- and main AFS compound-treated RAW264.7 cells stimulated by
      lipopolysaccharide (LPS). RESULTS: Anemone flaccida crude triterpenoid saponins
      inhibited redness and swelling of the right hind paw in the CIA model.
      Radiological and histological examinations indicated that inflammatory responses
      were reduced by AFS treatment. Moreover, comparing with untreated rats, serum TNF
      alpha (P = 0.0035 and P < 0.001) and IL-6 (P = 0.0058 and P = 0.0087) were lower
      in AFS-treated CIA rats at the dose of 200 and 400 mg/kg/day. AFS and its main
      compounds, including hederasaponin B, flaccidoside II, and hemsgiganoside B,
      significantly inhibited TNF-alpha (P = 0.0022, P = 0.013, P = 0.0015, and P =
      0.016) and IL-6 (P = 0.0175, P < 0.001, P < 0.001, and P < 0.001) production in
      LPS-treated RAW264.7 cells, respectively. CONCLUSIONS: Anemone flaccida crude
      triterpenoid saponins and its main bioactive components, including hederasaponin
      B, flaccidoside II, and hemsgiganoside B, decreased pro-inflammatory cytokine
      levels in a CIA rat model and LPS-induced RAW264.7 cells.

PMID- 26213565
TI  - The open abdomen, indications, management and definitive closure.
AB  - The indications for Open Abdomen (OA) are generally all those situations in which
      is ongoing the development an intra-abdominal hypertension condition (IAH), in
      order to prevent the development of abdominal compartmental syndrome (ACS). In
      fact all those involved in care of a critically ill patient should in the first
      instance think how to prevent IAH and ACS. In case of ACS goal directed therapy
      to achieve early opening and early closure is the key: paradigm of closure shifts
      to combination of therapies including negative pressure wound therapy and dynamic
      closure, in order to reduce complications and avoid incisional hernia. There have
      been huge studies and progress in survival of critically ill trauma and septic
      surgical patients: this in part has been through the great work of pioneers,
      scientific societies and their guidelines; however future studies and continued
      innovation are needed to better understand optimal treatment strategies and to
      define more clearly the indications, because OA by itself is still a morbid
      procedure. 

PMID- 26213570
TI  - Lipid production by the oleaginous yeast Yarrowia lipolytica using industrial by
      products under different culture conditions.
AB  - BACKGROUND: Microbial lipid production using renewable feedstock shows great
      promise for the biodiesel industry. RESULTS: In this study, the ability of a
      lipid-engineered Yarrowia lipolytica strain JMY4086 to produce lipids using
      molasses and crude glycerol under different oxygenation conditions and at
      different inoculum densities was evaluated in fed-batch cultures. The greatest
      lipid content, 31% of CDW, was obtained using a low-density inoculum, a constant
      agitation rate of 800 rpm, and an oxygenation rate of 1.5 L/min. When the strain
      was cultured for 450 h in a chemostat containing a nitrogen-limited medium
      (dilution rate of 0.01 h(-1); 250 g/L crude glycerol), volumetric lipid
      productivity was 0.43 g/L/h and biomass yield was 60 g CDW/L. The coefficient of
      lipid yield to glycerol consumption (Y L/gly) and the coefficient of lipid yield
      to biomass yield (Y L/X ) were equal to 0.1 and 0.4, respectively. CONCLUSIONS:
      These results indicate that lipids may be produced using renewable feedstock,
      thus providing a means of decreasing the cost of biodiesel production.
      Furthermore, using molasses for biomass production and recycling glycerol from
      the biodiesel industry should allow biolipids to be sustainably produced.

PMID- 26213571
TI  - Evaluation of hydrophobic micro-zeolite-mixed matrix membrane and integrated with
      acetone-butanol-ethanol fermentation for enhanced butanol production.
AB  - BACKGROUND: Butanol is regarded as an advanced biofuel that can be derived from
      renewable biomass. However, the main challenge for microbial butanol production
      is low butanol titer, yield and productivity, leading to intensive energy
      consumption in product recovery. Various alternative separation technologies such
      as extraction, adsorption and gas stripping, etc., could be integrated with
      acetone-butanol-ethanol (ABE) fermentation with improving butanol productivity,
      but their butanol selectivities are not satisfactory. The membrane-based
      pervaporation technology is recently attracting increasing attention since it has
      potentially desirable butanol selectivity. RESULTS: The performance of the
      zeolite-mixed polydimethylsiloxane (PDMS) membranes were evaluated to recover
      butanol from butanol/water binary solution as well as fermentation broth in the
      integrated ABE fermentation system. The separation factor and butanol titer in
      permeate of the zeolite-mixed PDMS membrane were up to 33.0 and 334.6 g/L at 80
      degrees C, respectively, which increased with increasing zeolite loading weight
      in the membrane as well as feed temperature. The enhanced butanol separation
      factor was attributed to the hydrophobic zeolites with large pore size providing
      selective routes preferable for butanol permeation. In fed-batch fermentation
      incorporated with pervaporation, 54.9 g/L ABE (34.5 g/L butanol, 17.0 g/L acetone
      and 3.4 g/L ethanol) were produced from 172.3 g/L glucose. The overall butanol
      productivity and yield increased by 16.0 and 11.1%, respectively, which was
      attributed to the alleviated butanol inhibition by pervaporation and
      reassimilation of acids for ABE production. The zeolite-mixed membrane produced a
      highly concentrated condensate containing 169.6 g/L butanol or 253.3 g/L ABE,
      which after phase separation easily gave the final product containing >600 g/L
      butanol. CONCLUSIONS: Zeolite loading in the PDMS matrix was attributed to
      improving the pervaporative performance of the membrane, showing great potential
      to recover butanol with high purity. Therefore, this zeolite-mixed PDMS membrane
      had the potential to improve biobutanol production when integrating with ABE
      fermentation.

PMID- 26213572
TI  - CFD modelling of sampling locations for early detection of spontaneous combustion
      in long-wall gob areas.
AB  - In this study, computational fluid dynamics (CFD) modeling was conducted to
      optimize gas sampling locations for the early detection of spontaneous heating in
      longwall gob areas. Initial simulations were carried out to predict carbon
      monoxide (CO) concentrations at various regulators in the gob using a bleeder
      ventilation system. Measured CO concentration values at these regulators were
      then used to calibrate the CFD model. The calibrated CFD model was used to
      simulate CO concentrations at eight sampling locations in the gob using a
      bleederless ventilation system to determine the optimal sampling locations for
      early detection of spontaneous combustion.

PMID- 26213573
TI  - CFD modelling of nitrogen injection in a longwall gob area.
AB  - This paper describes computational fluid dynamics (CFD) simulations conducted to
      investigate the effectiveness of N2 injection in an active panel and a sealed
      longwall gob area to prevent and suppress spontaneous heating of coal using
      various injection locations and flow rates. In the active panel simulations, a
      single longwall panel with a bleederless ventilation system was simulated. The
      spontaneous heating of crushed coal from pillars was simulated and N2 was
      injected from different locations on the headgate side and through boreholes from
      the surface. The N2 injection rate at each location was varied between 0.18 m3/s
      and 0.94 m3/s (380 and 2000 cfm). In the sealed longwall simulations, seal
      leakage rate was varied to determine its effect on N2 injection effectiveness.
      The results of this study should aid mine ventilation engineers in developing
      more effective N2 injection strategies to prevent and control spontaneous heating
      of coal in underground coal mines.

PMID- 26213575
TI  - Trisomy Xp and partial tetrasomy Xq resulting from gain of a rearranged X
      chromosome in a female fetus: pathogenic or not?
AB  - Cytogenetic analysis of chorionic villous sampling revealed a mosaic karyotype
      with gain of a rearranged X chromosome. Microarray and additional studies
      indicated that the rearranged X carried an inverted duplication, a deletion and a
      satellited Xqter. Gain of this rearranged X was confirmed by follow-up
      amniocentesis and postnatal cord blood sample. A full-term infant girl was
      delivered and showed normal physical findings at both birth and 21-month follow
      up examinations. Late replication studies demonstrated that the rearranged X was
      inactivated in all abnormal cells analyzed. Skewed X-inactivation may suppress
      the potentially deleterious effects of genomic imbalance; however, gain of X
      chromosomes, particularly rearranged X chromosomes, often presents challenges for
      prenatal genetic counseling. The gradation of clinical phenotype severity
      generally correlates with the number of additional X chromosomes. However, the X
      chromosome regions responsible for the abnormal phenotypes are poorly understood.
      This case will further elucidate the phenotypic effects of X inactivation and X
      chromosome abnormalities. 

PMID- 26213574
TI  - Association of circulating angiogenesis inhibitors and asymmetric dimethyl
      arginine with coronary plaque burden.
AB  - BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for the
      development and severity of coronary artery disease (CHD) and endothelial
      dysfunction. There is an increase in the circulating angiogenesis inhibitors
      endostatin (END), thrombospondin-2 (TSP), angiopoietin-2 (ANG) and the nitric
      oxide (NO) inhibitor asymmetric dimethyl arginine (ADMA) in CKD patients. The aim
      of this study was to evaluate associations of the serum level of these factors
      and of the related angiogenesis inhibitor, endoglin (ENG), with burden of
      coronary atherosclerosis. METHODS: One hundred twenty-two patients undergoing
      coronary angiography were recruited from the cardiac catheterization lab at a
      single center. The total burden of coronary plaque (mm(2)) and the presence of
      coronary collaterals were quantified using quantitative coronary angiography
      (QCA). Serum levels of angiogenesis inhibitors were measured by ELISA (ENG, END,
      and ANG), Luminex assay (TSP), or HLPC (ADMA), respectively. Associations with
      plaque burden and coronary collateral supply were analyzed in multi-variable
      linear and logistic regression models. RESULTS: There was no significant
      association found between levels of circulating ADMA, ENG, END, ANG, or TSP and
      coronary plaque burden or collateral formation. CONCLUSIONS: Our findings suggest
      that associations of circulating END, ENG, TSP, and ANG with cardiovascular
      mortality are unlikely to be mediated via direct effects on coronary plaque
      formation or by inhibition of collateral formation. Whether associations of these
      factors with mortality are mediated via local concentrations, myocardial tissue,
      or intra-plaque expression of these factors or by an effect on plaque
      vulnerability merits additional investigation.

PMID- 26213576
TI  - Periventricular heterotopia and white matter abnormalities in a girl with mosaic
      ring chromosome 6.
AB  - Ring chromosome 6 is a rare chromosome abnormality that arises typically de novo.
      The phenotypes can be highly variable, ranging from almost normal to severe
      malformations and neurological defects. We report a case of a 3-year-old girl
      with mosaic ring chromosome 6 who presented with being small for gestational age
      and intellectual disability, and whose brain MRI later revealed periventricular
      heterotopia and white matter abnormalities. Mosaicism was identified in
      peripheral blood cells examined by standard G-bands, mos
      46,XX,r(6)(p25q27)[67]/45,XX,-6[25]/46,XX,dic
      r(6:6)(p25q27:p25q27)[6]/47,XX,r(6)(p25q27) * 2[2]. Using array-comparative
      genomic hybridization, we identified terminal deletion of 6q27 (1.5 Mb) and no
      deletion on 6p. To our knowledge, this is the first report of periventricular
      heterotopia and white matter abnormalities manifested in a patient with ring
      chromosome 6. These central nervous system malformations are further discussed in
      relation to molecular genetics. 

PMID- 26213577
TI  - The catechol-O-methyltransferase inhibitor, tolcapone, increases the
      bioavailability of unmethylated (-)-epigallocatechin-3-gallate in mice.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), has been shown to inhibit cancer in vivo.
      EGCG, however, is rapidly methylated by catechol-O-methyl transferase (COMT),
      which reduces its cancer preventive efficacy. Tolcapone (TOL), is a clinically
      used COMT inhibitor. Here, we examined the effect of TOL on the bioavailability
      of EGCG in male CF-1 mice. Plasma and tissue levels of EGCG and its methyl
      metabolites were determined following intragastric administration of EGCG (100
      mg/kg), TOL (30 mg/kg), or the combination. In mice treated with EGCG,
      unmethylated plasma EGCG accounted for 63.4 % of the total. Co-administration of
      TOL increased this fraction to 87.9 %. In the urine, unmethylated EGCG accounted
      for 29.2 % of the total, whereas treatment with EGCG plus TOL increased this to
      81.8 %. Similar effects were observed in the major organs examined. TOL
      effectively inhibited the methylation of EGCG in vivo. Future studies should
      examine the cancer preventive effects of the combination.

PMID- 26213578
TI  - A reliable radiographic measurement for evaluation of normal distal tibiofibular
      syndesmosis: a multi-detector computed tomography study in adults.
AB  - BACKGROUND: Syndesmotic injury may be difficult to diagnose, and radiological
      evaluation is very important. The purpose of this study was to offer a series of
      reliable and repeatable normal tibiofibular syndesmosis parameters in diagnosing
      injuries of the syndesmosis. METHODS: Multi-detector computed tomography (MDCT)
      and radiographs of the distal tibiofibular syndesmosis in 484 cases were
      retrospectively reviewed. Relevant parameters included the tibiofibular clear
      space (TCS), the tibiofibular overlap (TFO), the depth of the incisura fibularis
      (IFD), and the height of the incisura fibularis (IFH), which were measured by
      novel three-dimensional (3-D) and two-dimensional (2-D) techniques. The distance
      between the measuring plane of the distal tibiofibular syndesmosis and the tibial
      plafond was measured. Intra- and inter-rater reliability was assessed by
      intraclass correlation coefficient (ICC) and the root mean square standard
      deviation (RMS-SD), to determine measurement precision. Sex differences of
      parameters were analyzed using analysis of covariance (ANCOVA) with body height
      as the covariate. Paired sample t-testing was used to compare parameters in
      different image modalities, including radiography, and 2-D and 3-D CT. RESULTS:
      The reliability of the 3-D images measurement (ICC range, 0.907 to 0.972) was
      greater than that for the 2-D axial images (ICC range, 0.895 to 0.927), and the
      AP view radiographs (ICC range, 0.742 to 0.838). The intra-rater RMS-SD of the 3
      D CT, 2-D CT and radiographic measurements were less than 0.94 mm, 0.26 mm, and
      2.87 mm, respectively. The measuring plane of the distal tibiofibular syndesmosis
      showed the sex difference, which was 12.1 mm proximal to the tibial plafond in
      the male group and 7.8 mm in the female group. In this plane, the parameters for
      tibiofibular syndesmosis were measured in different image modalities. All
      variables were significantly different between females and males (p < 0.05).
      CONCLUSIONS: 3-D measurement technique could be helpful to identify the precise
      measurement planes for syndesmosis, which were not at the fixed level above the
      tibial plafond because of the sex difference. In this plane, reliable measurement
      results could be provided, in either 2-D or 3-D MDCT images.

PMID- 26213580
TI  - S100A1 (S100 calcium binding protein A1).

PMID- 26213579
TI  - Effects of Souvenaid on plasma micronutrient levels and fatty acid profiles in
      mild and mild-to-moderate Alzheimer's disease.
AB  - INTRODUCTION: Circulating levels of uridine, selenium, vitamins B12, E and C,
      folate, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been
      shown to be lower in patients with Alzheimer's disease (AD) than in healthy
      individuals. These low levels may affect disease pathways involved in synapse
      formation and neural functioning. Here, we investigated whether, and to what
      extent, circulating levels of micronutrients and fatty acids can be affected by
      oral supplementation with Souvenaid (containing a specific nutrient combination),
      using data derived from three randomized clinical trials (RCT) and an open-label
      extension (OLE) study with follow-up data from 12 to 48 weeks. METHODS: Subjects
      with mild (RCT1, RCT2) or mild-to-moderate AD (RCT3) received active or control
      product once daily for 12-24 weeks or active product during the 24-week OLE
      following RCT2 (n = 212-527). Measurements included plasma levels of B vitamins,
      choline, vitamin E, selenium, uridine and homocysteine and proportions of DHA,
      EPA and total n-3 long-chain polyunsaturated fatty acids in plasma and
      erythrocytes. Between-group comparisons were made using t tests or non-parametric
      alternatives. RESULTS: We found that 12-24-week active product intake increased
      plasma and/or erythrocyte micronutrients: uridine; choline; selenium; folate;
      vitamins B6, B12 and E; and fatty acid levels of DHA and EPA (all p < 0.001). In
      the OLE study, similar levels were reached in former control product/initial
      active product users, whereas 24-week continued active product intake showed no
      suggestion of a further increase in nutrient levels. CONCLUSIONS: These data show
      that circulating levels of nutrients known to be decreased in the AD population
      can be increased in patients with mild and mild-tomoderate AD by 24-48-week oral
      supplementation with Souvenaid. In addition, to our knowledge, this is the first
      report of the effects of sustained dietary intake of uridine monophosphate on
      plasma uridine levels in humans. Uptake of nutrients is observed within 6 weeks,
      and a plateau phase is reached for most nutrients during prolonged intake, thus
      increasing the availability of precursors and cofactors in the circulation that
      may be used for the formation and function of neuronal membranes and synapses in
      the brain.

PMID- 26213581
TI  - A comparative drug utilisation study of the treatment of diabetes in Malaysia and
      Australia.
AB  - BACKGROUND: Once a disease of developed countries, type 2 diabetes mellitus
      (T2DM) has become widespread worldwide. For people with T2DM, achievement of
      therapeutic outcomes demands the rational and quality use of medicine. AIMS: The
      primary aim of this study was to examine the prevalence of diabetes and
      prescribing patterns of anti-diabetic medications in Australia and Malaysia.
      METHODS: The most recent, publicly available, statistical reports (2004-2008) on
      the use of medicines published in Australia and in Malaysia were evaluated.
      Defined daily doses (DDDs/1,000 population/day) were derived from the reports and
      used to rank and compare individual drug use. RESULTS: There was an increasing
      trend in the prevalence of diabetes in Australia, although there is a greater
      predicted increase in prevalence for Malaysia. While drugs used for the treatment
      of diabetes were not the most highly used drugs in Australia, their use increased
      during the study period, from 42.64 to 48.61 DDD/1,000/day. Anti-diabetic drugs
      were the most frequently dispensed class of drugs in Malaysia. Although the total
      consumption of anti-diabetic drugs in Malaysia decreased between 2006 and 2007
      (from 40.30 to 39.72), this was followed by a marked increase to 46.69 in 2008.
      There was a marked reduction in the dispensing of insulin in Malaysia from 2004
      to 2007 (7.77 to 3.23). CONCLUSION: The use of drugs to treat diabetes does not
      reflect the usage patterns found in Australia. Effective drug use reviews are
      required to ensure impartial access in middle- and low-income countries.

PMID- 26213582
TI  - Long-term glycaemic control (HbA1c), not admission glucose, predicts hospital re
      admission in diabetic patients.
AB  - BACKGROUND: Diabetic patients are commonly hyperglycaemic on presentation.
      Admission hyperglycaemia is associated with adverse outcomes, particularly
      prolonged hospitalisation. Improving inpatient glycaemia may reduce length of
      hospital stay (LOS) in diabetic patients. AIMS: To determine whether in-hospital
      recognition and treatment of admission hyperglycaemia in diabetic patients is
      associated with reduced LOS. METHODS: Medical records were reviewed from 1
      November 2011 to 31 May 2012 for 162 diabetic patients admitted with a blood
      glucose level (BGL) >=11.1mmol/L. In-hospital outcomes were compared. Stepwise
      multiple regression was used to evaluate factors contributing to LOS. RESULTS:
      Compared to the untreated individuals (n=67), hyperglycaemia treatment (n=95) was
      associated with a longer LOS (median eight vs. four days, p<0.01), higher HbA1c
      (9.0 vs. 7.3 per cent, p<0.01), more infections (50 vs. 25 per cent, p<0.01), and
      more patients with follow-up plans (35 vs. 10 per cent, p<0.01). Higher HbA1c was
      significantly related to more follow-up (rhos=0.30, n=110, p<0.01) with a trend
      to lower re-admission in those with follow-up plans (rhos=-1.41, n=162, p=0.07).
      CONCLUSION: Recognition and treatment of admission hyperglycaemia in diabetic
      patients was associated with longer LOS than if untreated. Contributory factors
      to LOS include: illness severity, infections, and higher HbA1c. Although follow
      up plans were few (27 per cent) for diabetic patients with hyperglycaemia, it was
      significantly more likely in those with higher HbA1c. Diabetic patients'
      complexities require timely multidisciplinary team involvement. Improved follow
      up care, particularly for hospitalised diabetic patients identified to have
      chronically poor glycaemic control, may help prevent future diabetic patient re
      admissions.

PMID- 26213583
TI  - Simultaneous gut colonisation and infection by ESBL-producing Escherichia coli in
      hospitalised patients.
AB  - BACKGROUND: Extended spectrum betalactamase (ESBL)-producing organisms are a
      major cause of hospital-acquired infections. ESBL-producing Escherichia coli (E.
      coli) have been recovered from the hospital environment. These drug-resistant
      organisms have also been found to be present in humans as commensals. The present
      investigation intended to isolate ESBL-producing E. coli from the gut of already
      infected patients; to date, only a few studies have shown evidence of the gut
      microflora as a major source of infection. AIMS: This study aimed to detect the
      presence of ESBL genes in E.coli that are isolated from the gut of patients who
      have already been infected with the same organism. METHODS: A total of 70 non
      repetitive faecal samples were collected from in-patients of our hospital. These
      in-patients were clinically diagnosed and were culture-positive for ESBL
      producing E. coli either from blood, urine, or pus. Standard microbiological
      methods were used to detect ESBL from clinical and gut isolates. Genes coding for
      major betalactamase enzymes such as bla CTX-M , bla TEM, and bla SHV were
      investigated by polymerase chain reaction (PCR). RESULTS: ESBL-producing E. coli
      was isolated from 15 (21 per cent) faecal samples of the 70 samples that were
      cultured. PCR revealed that out of these 15 isolates, the bla CTX-M gene was
      found in 13 (86.6 per cent) isolates, the bla TEM was present in 11 (73.3 per
      cent) isolates, and bla SHV only in eight (53.3 per cent) isolates. All 15
      clinical and gut isolates had similar phenotypic characters and eight of the 15
      patients had similar pattern of genes (bla TEM, bla CTX-M, and bla SHV) in their
      clinical and gut isolates. CONCLUSION: Strains with multiple betalactamase genes
      that colonise the gut of hospitalised patients are a potential threat and it may
      be a potential source of infection.

PMID- 26213584
TI  - Using care plans to better manage multimorbidity.
AB  - BACKGROUND: The health care for patients having two or more long-term medical
      conditions is fragmented between specialists, allied health professionals, and
      general practitioners (GPs), each keeping separate medical records. There are
      separate guidelines for each disease, making it difficult for the GP to
      coordinate care. The TrueBlue model of collaborative care to address key problems
      in managing patients with multimorbidity in general practice previously reported
      outcomes on the management of multimorbidities. We report on the care plan for
      patients with depression, diabetes, and/or coronary heart disease that was
      embedded in the TrueBlue study. METHODS: A care plan was designed around
      diabetes, coronary heart disease, and depression management guidelines to prompt
      implementation of best practices and to provide a single document for information
      from multiple sources. It was used in the TrueBlue trial undertaken by 400
      patients (206 intervention and 194 control) from 11 Australian general practices
      in regional and metropolitan areas. RESULTS: Practice nurses and GPs successfully
      used the care plan to achieve the guideline-recommended checks for almost all
      patients, and successfully monitored depression scores and risk factors, kept
      pathology results up to date, and identified patient priorities and goals.
      Clinical outcomes improved compared with usual care. CONCLUSION: The care plan
      was used successfully to manage and prioritise multimorbidity. Downstream
      implications include improving efficiency in patient management, and better
      health outcomes for patients with complex multimorbidities.

PMID- 26213585
TI  - Electronic activity trackers encourage family fun and fitness.

PMID- 26213587
TI  - Fractal Dimensions of Macromolecular Structures.
AB  - Quantifying the properties of macromolecules is a prerequisite for understanding
      their roles in biochemical processes. One of the less-explored geometric features
      of macromolecules is molecular surface irregularity, or 'roughness', which can be
      measured in terms of fractal dimension (D). In this study, we demonstrate that
      surface roughness correlates with ligand binding potential. We quantified the
      surface roughnesses of biological macromolecules in a large-scale survey that
      revealed D values between 2.0 and 2.4. The results of our study imply that
      surface patches involved in molecular interactions, such as ligand-binding
      pockets and protein-protein interfaces, exhibit greater local fluctuations in
      their fractal dimensions than 'inert' surface areas. We expect approximately 22 %
      of a protein's surface outside of the crystallographically known ligand binding
      sites to be ligandable. These findings provide a fresh perspective on
      macromolecular structure and have considerable implications for drug design as
      well as chemical and systems biology.

PMID- 26213586
TI  - Modulation of mu attenuation to social stimuli in children and adults with
      16p11.2 deletions and duplications.
AB  - BACKGROUND: Copy number variations (CNV) within the recurrent ~600 kb chromosomal
      locus of 16p11.2 are associated with a wide range of neurodevelopmental
      disorders, including autism spectrum disorder (ASD). However, little is known
      about the social brain phenotype of 16p11.2 CNV and how this phenotype is related
      to the social impairments associated with CNVs at this locus. The aim of this
      preliminary study was to use molecular subtyping to establish the social brain
      phenotype of individuals with 16p11.2 CNV and how these patterns relate to
      typical development and ASD. METHODS: We evaluated the social brain phenotype as
      expressed by mu attenuation in 48 children and adults characterized as
      duplication carriers (n = 12), deletion carriers (n = 12), individuals with
      idiopathic ASD (n = 8), and neurotypical controls (n = 16). Participants watched
      videos containing social and nonsocial motion during electroencephalogram (EEG)
      acquisition. RESULTS: Overall, only the typical group exhibited predicted
      patterns of mu modulation to social information (e.g., greater mu attenuation for
      social than nonsocial motion). Both 16p11.2 CNV groups exhibited more mu
      attenuation for nonsocial than social motion. The ASD group did not discriminate
      between conditions and demonstrated less mu attenuation compared to the typical
      and duplication carriers. Single-trial analysis indicated that mu attenuation
      decreased over time more rapidly for 16p11.2 CNV groups than the typical group.
      The duplication group did not diverge from typical patterns of mu attenuation
      until after initial exposure. CONCLUSIONS: These results indicate atypical but
      unique patterns of mu attenuation for deletion and duplication carriers,
      highlighting the need to continue characterizing the social brain phenotype
      associated with 16p11.2 CNVs.

PMID- 26213588
TI  - DNA methylation in ductal carcinoma in situ related with future development of
      invasive breast cancer.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-invasive
      lesion associated with an increased risk for future invasive ductal carcinoma.
      However, accurate risk stratification for development of invasive disease and
      appropriate treatment decisions remain clinical challenges. DNA methylation
      alterations are early events in the progression of cancer and represent emerging
      molecular markers that may predict invasive recurrence more accurately than
      traditional measures of DCIS prognosis. RESULTS: We measured DNA methylation
      using the Illumina HumanMethylation450K array of estrogen-receptor positive DCIS
      (n = 40) and adjacent-normal (n = 15) tissues from subjects in the New Hampshire
      Mammography Network longitudinal breast imaging registry. We identified locus
      specific methylation differences between DCIS and matched adjacent-normal tissue
      (95,609 CpGs, Q < 0.05). Among 40 DCIS cases, 13 later developed invasive disease
      and we identified 641 CpG sites that exhibited differential DNA methylation (P <
      0.01 and median |?beta| > 0.1) in these cases compared with age-matched subjects
      without invasive disease. The set of differentially methylated CpG loci
      associated with disease progression was enriched in homeobox-containing genes (P
      = 1.3E-09) and genes involved with limb morphogenesis (P = 1.0E-05). In an
      independent cohort, a subset of genes with progression-related differential
      methylation between DCIS and invasive breast cancer were confirmed. Further, the
      functional relevance of these genes' regulation by methylation was demonstrated
      in early stage breast cancers from The Cancer Genome Atlas database. CONCLUSIONS:
      This work contributes to the understanding of epigenetic alterations that occur
      in DCIS and illustrates the potential of DNA methylation as markers of DCIS
      progression.

PMID- 26213590
TI  - On the Supposed Evidence for Libertarian Paternalism.
AB  - Can the general public learn to deal with risk and uncertainty, or do authorities
      need to steer people's choices in the right direction? Libertarian paternalists
      argue that results from psychological research show that our reasoning is
      systematically flawed and that we are hardly educable because our cognitive
      biases resemble stable visual illusions. For that reason, they maintain,
      authorities who know what is best for us need to step in and steer our behavior
      with the help of "nudges." Nudges are nothing new, but justifying them on the
      basis of a latent irrationality is. In this article, I analyze the scientific
      evidence presented for such a justification. It suffers from narrow logical
      norms, that is, a misunderstanding of the nature of rational thinking, and from a
      confirmation bias, that is, selective reporting of research. These two flaws
      focus the blame on individuals' minds rather than on external causes, such as
      industries that spend billions to nudge people into unhealthy behavior. I
      conclude that the claim that we are hardly educable lacks evidence and forecloses
      the true alternative to nudging: teaching people to become risk savvy.

PMID- 26213589
TI  - Heterogeneity of Mitral Leaflet Matrix Composition and Turnover   Correlates with
      Regional Leaflet Strain.
AB  - To determine how extracellular matrix and contractile valvular cells contribute
      to the heterogeneous motion and strain across the mitral valve (MV) during the
      cardiac cycle, regional MV material properties, matrix composition, matrix
      turnover, and cell phenotype were related to regional leaflet strain. Radiopaque
      markers were implanted into 14 sheep to delineate the septal (SEPT), lateral
      (LAT), and anterior and posterior commissural leaflets (ANT-C, POST-C).
      Videofluoroscopy imaging was used to calculate radial and circumferential
      strains. Mechanical properties were assessed using uniaxial tensile testing and
      micropipette aspiration. Matrix composition and cell phenotypes were
      immunohistochemically evaluated within each leaflet region [basal leaflet (BL),
      mid-leaflet (ML), and free edge]. SEPT-BL segments were stiffer and stronger than
      other valve tissues, while LAT segments demonstrated more extensibility and
      strain. Collagens I and III in SEPT were greater than in LAT, although LAT showed
      greater collagen turnover [matrix metalloprotease (MMP)-13, lysyl oxidase] and
      cell activation [smooth muscle alpha-actin (SMaA), and non-muscle myosin (NMM)].
      MMP13, NMM, and SMaA were strongly correlated with each other, as well as with
      radial and circumferential strains in both SEPT and LAT. SMaA and MMP13 in POST-C
      ML was greater than ANT-C, corresponding to greater radial strains in POST-C.
      This work directly relates leaflet strain, material properties, and matrix
      turnover, and suggests a role for myofibroblasts in the heterogeneity of leaflet
      composition and strain. New approaches to MV repair techniques and ring design
      should preserve this normal coupling between leaflet composition and motion.

PMID- 26213591
TI  - Quantifying Maternal and Paternal Disease History Using Log-Rank Score with an
      Application to a National Cohort Study.
AB  - Both maternal and paternal disease history can be important predictors of the
      risk of common conditions such as heart disease or cancer because of shared
      environmental and genetic risk factors. Sometimes maternal and paternal history
      can have remarkably different effects on offspring's status. The results are
      often affected by how the maternal and paternal disease histories are quantified.
      We proposed using the log-rank score (LRS) to investigate the separate effect of
      maternal and paternal history on diseases, which takes parental disease status
      and the age of their disease onset into account. Through simulation studies, we
      compared the performance of the maternal and paternal LRS with simple binary
      indicators under two different mechanisms of unbalanced parental effects. We
      applied the LRS to a national cohort study to further segregate family risks for
      heart diseases. We demonstrated using the LRS rather than binary indicators can
      improve the prediction of disease risks and better discriminate the paternal and
      maternal histories. In the real study, we found that the risk for stroke is
      closely related with maternal history but not with paternal history and that
      maternal and paternal disease history have similar impact on the onset of
      myocardial infarction.

PMID- 26213592
TI  - [Penile and scrotal avulsion caused by zebu horns].

PMID- 26213593
TI  - [Fanconi anemia: report of a new case].

PMID- 26213594
TI  - Primary hepatoid carcinoma of the ovary: a case report.
AB  - Primary hepatoid carcinoma of the ovary (HCO) is a very rare type of high-grade
      invasive malignant ovarian tumor with hepatic differentiation and production of
      alpha-fetoprotein (AFP). We describe a 78-year-old Moroccan woman who presented
      to our hospital with abdominal distension and purplish nodules infiltrating the
      para umbilical skin with weight loss and impairment of her performance status.
      Excisional biopsy of the para umbilical nodule revealed a cutaneous localization
      of moderately differentiated adenocarcinoma and pelvic ultrasonography noted the
      presence of a tumoral right adnexal mass. The patient underwent an exploratory
      laparoscopy which found peritoneal carcinomatosis with pelvic adhesions allowing
      only a peritoneal biopsy. Diagnosis of primary hepatoid carcinoma of the ovary
      was established on the basis of classic histopathologic findings,
      immunohistochemical staining and marked elevation in serum of alpha-fetoprotein
      more than the carbohydrate antigen 125. The patient received 3 cycles of
      chemotherapy based on Carboplatin and Paclitaxel with disease progression. No
      second line chemotherapy was given because of the drop of patient's performance
      status to 3. The patient died one month later. 

PMID- 26213595
TI  - [Quantification of antimalarial input requirements: a contribution in updating
      hypothesis for the quantification of management inputs for severe malaria in the
      Democratic Republic of Congo].

PMID- 26213596
TI  - [Reduction of the dislocation of the radial head in the context of exostoses
      disease: report of a case].

PMID- 26213597
TI  - Forensic odontological observations in the victims of DANA air crash.
AB  - INTRODUCTION: Forensic odontology or forensic dentistry is that aspect of
      forensic science that uses the application of dental science for the
      identification of unknown human remains and bite marks. Deaths resulting from
      mass disasters such as plane crash or fire incidence have always been given mass
      burial in Nigeria. This was obviously due to the fact that Forensic Pathologists
      whose roles involve disaster victim identification were not available at that
      time. However, in the DANA air crash in Lagos in 2012, the Forensic pathologist
      and dental teams were invited for the first time to identify the victims. The
      objectives of this paper are to identify the extent of victims' identification
      using Forensic odontology alone and its combination with DNA analysis. It also
      presents the pattern of fractures seen in the mandible and maxilla of the
      victims. METHODS: The bodies were dissected using following the standard protocol
      dissection. Prior to this all the victims had Dental Radiological Examination.
      The oral cavities were exposed after which the Odontology team was invited for
      photographing first, followed by dental charting. Fractures of the mandible,
      maxilla including the anatomical regions were all recorded and photographed.
      Dental prosthesis, restorations, crowns and bridge and other findings were also
      noted, recorded and compared with ante mortem records where available. RESULTS: A
      total of 152 bodies were recovered from the crash site while 148 victims were
      eventually identified through a combination of DNA analysis and forensic
      odontology. This represented 97.4%. Forensic odontology was the primary
      identifier in 10%. There were no fingerprinting information in this country at
      present therefore, it could not be used. A total of 89 (60%) were males while
      females accounted for 59(40%). This gives a ratio of 1.5:1. Most of the victims
      were in the age group 30-49 years; this represented 52% of the victims while the
      least involved age groups were victims above 60 years of age which accounted for
      only 4.7%. Mandibular fractures were seen in 29 victims, maxilla in 15, combined
      mandibullo/maxillary in 15 victims, while 89 victims had no jaw fracture. The
      most common area of fracture in the mandible was the body which accounted for
      36.4%, closely followed by parasymphyseal region 31.9%, symphyseal 22.7% and the
      angle 9.0%. The most common fracture in the maxillae was palatal split fracture
      which accounted for 52%, this was followed by pterygoid 24%, alveolar 8% and
      multiple locations 16%. CONCLUSION: A combination of DNA analysis and forensic
      odontology was able to identify a total of 148 victims out of 152 representing
      97.4%. Forensic odontology was the primary identifier in only 10%. In the latter,
      poor and lack of dental records were responsible for this very low figure. The
      most common area of fracture in the mandible was the body which accounted for
      36.4%, while that of the maxillae was palatal fracture which accounted for 52%.
      Padding of the back of the seats in the aircraft should be canvassed for to
      provide Cushing effect for passengers.

PMID- 26213598
TI  - Spontaneous Rhinorrhea mimicking sinusitis.
AB  - Spotaneous or non-traumatic cerebrospinal fluid rhinorrhea is an uncommon
      condition and may present a diagnostic challenge to clinicians. This condition is
      often being misdiagnosed for allergic rhintis or chronic sinusitis since the
      precipitating cause is not readily apperent in most patients. The mechanism of
      rhinorrhea is stil not completely clarified. We describe a case of this condition
      occuring in association with allergic rhinitis and sinusitis. A 52 year-old,
      obese female patient presented with two weeks history of bilateral clear nasal
      discharge and postural headache. Sample of nasal discharge tested for glucose and
      protein. The result was that the collection fluid was cerebrospinal fluid. The
      origin of cerebrospinal fluid fistula could not be identified despite the
      diagnostic tests. 

PMID- 26213599
TI  - [Association sarcoidosis and Horton disease: report of a case].

PMID- 26213600
TI  - [Evaluation of tolerance and efficacy of the treatment of chronic viral hepatitis
      C in homozygous sickle cell patients].

PMID- 26213601
TI  - [Urinary tract infections in chronic renal failure patients hospitalized in
      nephrology department: bacteriological profile and risk factors].

PMID- 26213603
TI  - [Caesarean scar pregnancies: about a case report and review of literature].

PMID- 26213602
TI  - Malignant salivary gland tumours of the head and neck region: a single
      institutions review.
AB  - INTRODUCTION: Malignant salivary gland tumours (MSGTs) comprise about 3% of all
      head and neck cancers; they demonstrate an unpredictable clinical course. The
      purpose of this study is to review MSGTs seen at a tertiary Health centre, and
      compare findings with those of previous studies. METHODS: The records of the
      Department of Oral Pathology and the Department of Pathology, University College
      Hospital Ibadan were reviewed over a 19 year period and lesions diagnosed as
      MSGTs according to 2005 WHO histological classification were analysed for age,
      gender and site using SPSS for Windows (version 20.0; SPSS Inc. Chicago, IL).
      RESULTS: MSGTs were more common in males (55.2%) than females (44.8%). The mean
      age of was 47.9 (+/-17.0) years and peak age was the fifth decade. The parotid
      gland was the commonest site with 62 (28.1%) cases. The palate was the commonest
      intraoral site with 61(27.6%). The nose with 19 (8.6%) was the commonest minor
      extra-oral site. CONCLUSION: The findings were essentially similar to reports
      from Europe and America. Adenoid Cystic Carcinoma was the most common MSGT in
      this series. A high proportion of salivary gland tumours in sublingual gland were
      malignant. The reason(s) for high proportion of MSGTs in sublingual glands
      requires further investigation.

PMID- 26213604
TI  - [Isolated Adie pupil: about a case].

PMID- 26213606
TI  - Alkyl-Nitrile Adlayers as Probes of Plasmonically Induced Electric Fields.
AB  - Vibrational Stark shifts observed from mercaptoalkyl monolayers on surface
      enhanced Raman (SERS) active materials are reported to provide a direct
      measurement of the local electric field around plasmonic nanostructures. Adlayers
      of CN-, p-mercaptobenzonitrile, and n-mercaptobutylnitrile were adsorbed to a
      heterogeneous nanostructured Ag surface. The frequency of the CN moiety was
      observed to shift in a correlated fashion with the SERS intensity. These shifts
      are attributed to a vibrational Stark shift arising from rectification of the
      optical field, which gives rise to a DC potential on the surface. All three
      molecules showed CN Stark shifts on the plasmonic surfaces. P
      mercaptobenzonitrile is observed to be a well-behaved probe of the electric
      field, providing a narrow spectral line, suggesting a more uniform orientation on
      the surface. The utility of p-mercaptobenzonitrile was demonstrated by
      successfully assessing the electric field between gold nanoparticles adsorbed to
      a monolayer of the nitrile on a flat gold surface. A model is presented where the
      Stark shift of the alkyl-nitrile probe can be correlated to optical field,
      providing an intensity independent measurement of the local electric field
      environment.

PMID- 26213607
TI  - Older soft tissue sarcoma patients experience increased rates of venous
      thromboembolic events: a retrospective cohort study of SEER-Medicare data.
AB  - BACKGROUND: Venous thromboembolic co-morbidities can have a significant impact on
      treatment response, treatment options, quality of life, and ultimately, survival
      from cancer. There is a dearth of published information on venous thromboembolic
      co-morbidity among older soft tissue sarcoma patients. METHODS: SEER-Medicare
      linked data (1993-2005) was utilized for this retrospective cohort analysis (n =
      3,480 soft tissue sarcoma patients). Non-cancer patients were frequency-matched
      by age to cancer patients at a ratio of 1:1; coverage and follow-up requirements
      were the same as for soft tissue sarcoma cases. Venous thromboembolic events were
      divided into three groups of interest: deep vein thrombosis, pulmonary embolism,
      and other thromboembolic events. Relative incidence rates of venous
      thromboembolic events in soft tissue sarcoma patients with a recent history of
      cardiovascular event or venous thromboembolic event (12 months before diagnosis)
      versus soft tissue sarcoma patients without such a recent history were calculated
      using the Cox proportional hazard models. The Cox proportional hazard model was
      used to build predictive models to identify important risk factors for each
      venous thromboembolic event of interest among soft tissue sarcoma patients.
      Relative incidence rate of VTEs in cancer patients (12 months after diagnosis)
      versus non-cancer cases (12 months after index date) was calculated using
      multivariable Cox proportional hazard models. RESULTS: We observed that among
      older soft tissue sarcoma patients, 10.6% experienced a deep vein thrombosis,
      3.0% experienced a pulmonary embolism, and 3.1% experienced other thromboembolic
      events in the 12 months after sarcoma diagnosis. On average, 60% of venous
      thromboembolic events occurred in the first 90 days after sarcoma diagnosis. The
      highest rates of deep vein thrombosis and pulmonary embolism after sarcoma
      diagnosis were seen in patients with sarcoma not otherwise specified (deep vein
      thrombosis: 204/1,000 p-y and pulmonary embolism: 50/1,000 p-y). Recent history
      of a venous thromboembolic event was the strongest predictor of a subsequent
      venous thromboembolic event after soft tissue sarcoma diagnosis. CONCLUSION:
      Venous thromboembolic events are common and serious co-morbidities that should be
      closely monitored in older soft tissue sarcoma patients.

PMID- 26213605
TI  - Regulatory Interactions in the Bone Marrow Microenvironment.
AB  - Hematopoietic stem cells (HSCs) are the immature, pluripotent cells from which
      all myeloid and lymphoid cell types originate. As stem cells, HSCs are capable of
      two very different fate choices: self-renewal, ensuring they will persist
      throughout the lifetime of an organism, and differentiation to mature progeny.
      Therapeutic applications of HSCs include their routine use in stem cell
      transplantation to treat hematopoietic malignancies or bone marrow failure.
      Research and clinical experience have provided tools for the immunophenotypic
      identification and functional analysis of HSCs and there is increasing evidence
      suggesting that HSC regulation is greatly influenced by signals from their niches
      in the bone marrow. Although they represent one of the most rigorously studied
      stem cell types, still more remains to be known about how HSCs are regulated and
      respond to stress conditions.

PMID- 26213609
TI  - Differential recolonization of Atlantic intertidal habitats after disturbance
      reveals potential bottom-up community regulation.
AB  - In the spring of 2014, abundant sea ice that drifted out of the Gulf of St.
      Lawrence caused extensive disturbance in rocky intertidal habitats on the
      northern Atlantic coast of mainland Nova Scotia, Canada. To monitor recovery of
      intertidal communities, we surveyed two wave-exposed locations in the early
      summer of 2014. Barnacle recruitment and the abundance of predatory dogwhelks
      were low at one location (Tor Bay Provincial Park) but more than 20 times higher
      at the other location (Whitehead). Satellite data indicated that the abundance of
      coastal phytoplankton (the main food source for barnacle larvae) was consistently
      higher at Whitehead just before the barnacle recruitment season, when barnacle
      larvae were in the water column. These observations suggest bottom-up forcing of
      intertidal communities. The underlying mechanisms and their intensity along the
      NW Atlantic coast could be investigated through studies done at local and
      regional scales. 

PMID- 26213608
TI  - Exploratory study of tolerability and immunological effect of a short up-dosing
      immunotherapy phase with a standardised allergen extract derived from pollen of
      Olea europaea.
AB  - BACKGROUND: A new subcutaneous specific immunotherapy (SCIT) product adsorbed on
      aluminium hydroxide has been developed with a short and simplified up-dosing
      phase, containing a biologically standardized allergen pollen extract from Olea
      europaea. OBJECTIVE: To assess the tolerability profile of the updosing phase and
      its immunological effect, in terms of specific IgG4 and IgE levels and immediate
      skin reactivity. MATERIAL AND METHODS: The study was an exploratory, multi
      centre, open-label, single-arm, phase II/III clinical trial. Adults with a
      clinical history of allergic rhinoconjunctivitis with/without asthma due to
      sensitization to olive pollen were selected. Five up-dosing doses (300, 600,
      3000, 6000 and 15000SQ+) were administered at weekly intervals, followed by a
      maintenance dose (15000SQ+) after 2 weeks. Adverse events were collected during
      the 30 min observation period after injections, after a telephone contact 2 days
      after each visit, and after reviewing the subjects' diary. IgG4 and IgE levels
      and immediate skin reactivity were evaluated at the beginning and at the end of
      the trial. RESULTS: Ninety-three subjects were included in the trial (mean age,
      35.7 +/- 10.3 years; women, 66.7 %). A total of 95 adverse drug reactions, all
      mild in intensity and non-serious, were reported during the trial: 85 local in
      34.4 % subjects, 9 systemic in 4.3 % subjects and one non-specific (grade 0).
      Within 6 weeks, significant changes in IgG4 and IgE levels and in immediate skin
      reactivity to Olea europaea were accomplished. CONCLUSION: This new SCIT derived
      from pollen of Olea europaea presented a good tolerability profile and induced
      significant immunological responses already after a 6 week treatment. However,
      the non-controlled design may limit the interpretation of these results. TRIAL
      REGISTRATION: EudraCT no: 2011-004852-20; ClinicalTrials.gov Identifier:
      NCT01674595.

PMID- 26064469
TI  - ActivePapers: a platform for publishing and archiving computer-aided research.
AB  - The lack of replicability and reproducibility of scientific studies based on
      computational methods has lead to serious mistakes in published scientific
      findings, some of which have been discovered and publicized recently. Many
      strategies are currently pursued to improve the situation. This article reports
      the first conclusions from the ActivePapers project, whose goal is the
      development and application of a computational platform that allows the
      publication of computational research in a form that enables installation-free
      deployment, encourages reuse, and permits the full integration of datasets and
      software into the scientific record. The main finding is that these goals can be
      achieved with existing technology, but that there is no straightforward way to
      adapt legacy software to such a framework. 

PMID- 26213611
TI  - Case Report: Pulmonary Alveolar Calcification as a Result of Severe Hypercalcemia
      due to Acute Lymphoblatic Leukemia.
AB  - Severe hypercalcemia is a rare metabolic disorder in pediatric medicine. This
      report describes a rare case of severe hypercalcemia and its clinical
      manifestations in a 2-year-old toddler. The radiological findings caused by
      hypercalcemia and osteolysis were emblematic of the osteolytic lesions.
      Hypercalcemia led to massive pulmonary alveolar calcification. The hypercalcemia
      was successfully treated with pamidronate, a bisphosphonate drug class. Further
      investigation resulted in a diagnosis of acute lymphoblastic leukemia (ALL). The
      patient is currently on chemotherapy and has a favorable prognosis. Although
      severe hypercalcemia alone is an unusual finding as the first sign for ALL, this
      should be considered, not to mention the radiological images resulted from
      calcium deposits. 

PMID- 26213612
TI  - Neutrophil Lymphocyte Ratio as a predictor of systemic inflammation - A cross
      sectional study in a pre-admission setting.
AB  - BACKGROUND: Neutrophil:lymphocyte ratio (NLR)  is an emerging biomarker that is
      used to predict postoperative mortality and morbidity in cardiac and cancer
      surgeries. The association of this biomarker with systemic illness and its
      usefulness in risk assessment of preoperative patients has not been fully
      elucidated. OBJECTIVES: To determine the prevalence of elevated NLR in
      preoperative patients and to examine the relationship between elevated NLR and
      the presence of systemic illnesses as well as anaesthesia risk indices such as
      American Society of Anesthesia (ASA) and the revised cardiac risk index (RCRI)
      scores.   DESIGN: Cross-sectional study Setting: Anaesthesia pre-admission
      clinic, Toronto Western Hospital, Toronto, Canada Patients: We evaluated 1117 pre
      operative patients seen at an anesthesia preadmission clinic. RESULTS: NLR was
      elevated (>3.3) in 26.6% of target population. In multivariate analysis,
      congestive cardiac failure, diabetes mellitus and malignancy were independent
      risk factors predicting raised NLR. After regression analysis, a relationship
      between NLR and ASA score (Odds Ratio 1.78; 95% CI: 1.42-2.24) and revised
      cardiac risk index (RCRI, odds ratio 1.33; 95% CI: 1.09-1.64, p-value: 0.0063)
      was observed. CONCLUSIONS:  NLR was elevated (> 3.3) in 26.6% of patients.
      Congestive cardiac failure and malignancy were two constant predictors of
      elevated NLR at >3.3 and > 4.5. There was a strong association between NLR and
      anesthesia risk scoring tools of ASA and RCRI.

PMID- 26213613
TI  - Case Report: Pre- and postnatal management of an allantoic cyst with patent
      urachus and single umbilical artery.
AB  - Patent urachus is a rare congenital abnormality. Since its first description by
      Cabriolus in 1550, few cases have been reported. A 26-year-old Vietnamese
      primigravida presented at 20 weeks of gestation for evaluation of a cystic mass
      in the umbilical cord, which was first discovered at week 13 of pregnancy by
      ultrasound scan. The cystic mass originated from the root of the umbilical cord,
      connected to the urinary bladder, and no intestinal contents were enclosed
      within. Doppler ultrasound assessment showed that the single umbilical artery
      existed within the normal range. The progression of the umbilical cyst continued
      to be screened, but the mass disappeared on ultrasound images at 27 weeks of
      gestation. This led to the consideration of the cyst's rupture. After 38
      gestational weeks, the pregnant woman delivered a 3350g male infant via cesarean
      section because of an obstructed vaginal labor. The following days, a stream of
      urine was recorded leaking out from the umbilical mass whenever he cried. Seven
      weeks after delivery, an open surgical approach was successfully performed. The
      baby is now 43 months of age, growing and developing normally. Since an allantoic
      cyst with patent urachus is a rare clinical entity, early discovery, close
      monitoring and accurate diagnosis through ultrasound in the prenatal period may
      consequently allow clinicians to have suitable attitudes towards management when
      the infant is born. 

PMID- 26213614
TI  - An open ecosystem engagement strategy through the lens of global food safety.
AB  - The Global Food Safety Partnership (GFSP) is a public/private partnership
      established through the World Bank to improve food safety systems through a
      globally coordinated and locally-driven approach. This concept paper aims to
      establish a framework to help GFSP fully leverage the potential of open models.
      In preparing this paper the authors spoke to many different GFSP stakeholders who
      asked questions about open models such as: what is it?what's in it for me?why use
      an open rather than a proprietary model?how will open models generate equivalent
      or greater sustainable revenue streams compared to the current "traditional"
      approaches?  This last question came up many times with assertions that
      traditional service providers need to see opportunity for equivalent or greater
      revenue dollars before they will buy-in. This paper identifies open value
      propositions for GFSP stakeholders and proposes a framework for creating and
      structuring that value. Open Educational Resources (OER) were the primary open
      practice GFSP partners spoke to us about, as they provide a logical entry point
      for collaboration. Going forward, funders should consider requiring that
      educational resources and concomitant data resulting from their sponsorship
      should be open, as a public good. There are, however, many other forms of open
      practice that bring value to the GFSP. Nine different open strategies and tactics
      (Appendix A) are described, including: open content (including OER and open
      courseware), open data, open access (research), open government, open source
      software, open standards, open policy, open licensing and open hardware. It is
      recommended that all stakeholders proactively pursue "openness" as an operating
      principle. This paper presents an overall GFSP Open Ecosystem Engagement Strategy
      within which specific local case examples can be situated. Two different case
      examples, China and Colombia, are presented to show both project-based and crowd
      sourced, direct-to-public paths through this ecosystem. 

PMID- 26213615
TI  - Understanding carbon regulation in aquatic systems - Bacteriophages as a model.
AB  - The bacteria and their phages are the most abundant constituents of the aquatic
      environment, and so represent an ideal model for studying carbon regulation in an
      aquatic system. The microbe-mediated interconversion of bioavailable organic
      carbon (OC) into dissolved organic carbon (DOC) by the microbial carbon pump
      (MCP) has been suggested to have the potential to revolutionize our view of
      carbon sequestration. It is estimated that DOC is the largest pool of organic
      matter in the ocean and, though a major component of the global carbon cycle, its
      source is not yet well understood. A key element of the carbon cycle is the
      microbial conversion of DOC into inedible forms. The primary aim of this study is
      to understand the phage conversion from organic to inorganic carbon during phage
      host interactions. Time studies of phage-host interactions under controlled
      conditions reveal their impact on the total carbon content of the samples and
      their interconversion of organic and inorganic carbon compared to control
      samples. A total organic carbon (TOC) analysis showed an increase in inorganic
      carbon content by 15-25 percent in samples with bacteria and phage compared to
      samples with bacteria alone. Compared to control samples, the increase in
      inorganic carbon content was 60-70-fold in samples with bacteria and phage, and
      50-55-fold for samples with bacteria alone. This study indicates the potential
      impact of phages in regulating the carbon cycle of aquatic systems. 

PMID- 26213617
TI  - Characterization of an APC Promoter 1B deletion in a Patient Diagnosed with
      Familial Adenomatous Polyposis via Whole Genome Shotgun Sequencing.
AB  - Recently, deletions have been identified and published as causal for Familial
      Adenomatous Polyposis in the 1B promoter region of the APC gene.  Those deletions
      were measured using multiplex ligation-dependent probe amplification.  Here, we
      present and characterize an ~11kb deletion identified by whole genome shotgun
      sequencing.  The deletion occurred in a patient diagnosed with Familial
      Adenomatous Polyposis, and was located on chr5, between bases 112,034,824 and
      112,045,845, fully encompassing the 1B promoter region of the APC gene.   Results
      are presented here that include the sequence evidence supporting the presence of
      the deletion as well as base level characterization of the deletion site.  These
      results demonstrate the capacity of whole genome sequencing for the detection of
      large structural variants in single individuals. 

PMID- 26213616
TI  - Relationships between activation level, knowledge, self-efficacy, and self
      management behavior in heart failure patients discharged from rural hospitals.
AB  - Non-adherence to self-management guidelines accounted for 50% of hospital
      readmissions in heart failure patients. Evidence showed that patient activation
      affects self-management behaviors in populations living with chronic conditions.
      The purpose of this study was to describe patient activation level and its
      relationship with knowledge, self-efficacy and self-management behaviors in heart
      failure patients discharged from rural hospitals. Our study populations were
      recruited from two hospitals in rural areas of Nebraska. We found that two-thirds
      of the participants reported low activation levels (e.g., taking no action to
      manage their heart failure condition). In addition, low patient activation levels
      were associated with inadequate heart failure knowledge (p=.005), low self
      efficacy (p<.001) and low engagement in heart failure self-management behaviors
      (p<.001) after discharge from hospital. 

PMID- 26213618
TI  - Molecular Epidemiology of Hepatocellular Carcinoma.

PMID- 26213619
TI  - Personalized management of hepatocellular carcinoma based on molecular
      information: future prospects.

PMID- 26213620
TI  - Colonization with resistant microorganisms in patients transferred from abroad:
      who needs to be screened?
AB  - BACKGROUND: While multi-drug resistant organisms (MDRO) are a global phenomenon,
      there are significant regional differences in terms of prevalence. Traveling to
      countries with a high MDRO prevalence increases the risk of acquiring such an
      organism. In this study we determined risk factors for MDRO colonization among
      patients who returned from a healthcare system in a high-prevalence area (so
      called transfer patients). Factors predicting colonization could serve as
      screening criteria to better target those at highest risk. METHODS: This
      screening study included adult patients who had been exposed to a healthcare
      system abroad or in a high-prevalence region in Switzerland over the past six
      months and presented to our 950-bed tertiary care hospital between January 1,
      2012 and December 31, 2013, a 24-month period. Laboratory screening tests focused
      on Gram-negative MDROs and methicillin-resistant Staphylococcus aureus (MRSA).
      RESULTS: A total of 235 transfer patients were screened and analyzed, of which 43
      (18 %) were positive for an MDRO. Most of them yielded Gram-negative bacteria
      (42; 98 %), with only a single screening revealing MRSA (2 %); three screenings
      showed a combination of Gram-negative bacteria and MRSA. For the risk factor
      analysis we focused on the 42 Gram-negative MDROs. Most of them were ESBL
      producing Escherichia coli and Klebsiella pneumoniae while only two were
      carbapenemase producers. In univariate analysis, factors associated with
      screening positivity were hospitalization outside of Europe (p < 0.001), surgical
      procedure in a hospital abroad (p = 0.007), and - on admission to our hospital -
      active infection (p = 0.002), antibiotic treatment (p = 0.014) and presence of
      skin lesions (p = 0.001). Only hospitalization outside of Europe (Odds Ratio, OR
      3.2 (95 % CI 1.5- 6.8)) and active infection on admission (OR 2.7 (95 % CI 1.07-
      6.6)) remained as independent predictors of Gram-negative MDRO colonization.
      CONCLUSION: Our data suggest that a large proportion of patients (i.e., 82 %)
      transferred to Switzerland from hospitals in high MDRO prevalence areas are
      unnecessarily screened for MDRO colonization. Basing our screening strategy on
      certain criteria (such as presence of skin lesions, active infection, antibiotic
      treatment, history of a surgical procedure abroad and hospitalization outside of
      Europe) promises to be a better targeted and more cost-effective strategy.

PMID- 26213487
TI  - Measurement of the top quark mass in the [Formula: see text] and [Formula: see
      text] channels using [Formula: see text] [Formula: see text] ATLAS data.

PMID- 26213621
TI  - Genotype-phenotype relationship in hereditary amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron
      disease. It is characterized by neuronal loss and degeneration of the upper motor
      neurons (UMNs) and lower motor neurons (LMNs), and is usually fatal due to
      respiratory failure within 3-5 years of onset. Although approximately 5-10 % of
      patients with ALS have an inherited form of the disease, the distinction between
      hereditary and apparently sporadic ALS (SALS) seems to be artificial. Thus,
      genetic factors play a role in all types of ALS, to a greater or lesser extent.
      During the decade of upheaval, the evolution of molecular genetics technology has
      rapidly advanced our genetic knowledge about the causes of ALS, and the
      relationship between the genetic subtypes and clinical phenotype. In this review,
      we will focus on the possible genotype-phenotype correlation in hereditary ALS.
      Uncovering the identity of the genetic factors in ALS will not only improve the
      accuracy of ALS diagnosis, but may also provide new approaches for preventing and
      treating the disease. 

PMID- 26213623
TI  - The assessment of fidelity in a motor speech-treatment approach.
AB  - OBJECTIVE: To demonstrate the application of the constructs of treatment fidelity
      for research and clinical practice for motor speech disorders, using the Prompts
      for Restructuring Oral Muscular Phonetic Targets (PROMPT) Fidelity Measure (PFM).
      Treatment fidelity refers to a set of procedures used to monitor and improve the
      validity and reliability of behavioral intervention. While the concept of
      treatment fidelity has been emphasized in medical and allied health sciences,
      documentation of procedures for the systematic evaluation of treatment fidelity
      in Speech-Language Pathology is sparse. METHODS: The development and iterative
      process to improve the PFM, is discussed. Further, the PFM is evaluated against
      recommended measurement strategies documented in the literature. This includes
      evaluating the appropriateness of goals and objectives; and the training of
      speech-language pathologists, using direct and indirect procedures. Three expert
      raters scored the PFM to examine inter-rater reliability. RESULTS: Three raters,
      blinded to each other's scores, completed fidelity ratings on three separate
      occasions. Inter-rater reliability, using Krippendorff's Alpha, was >80% for the
      PFM on the final scoring occasion. This indicates strong inter-rater reliability.
      CONCLUSION: The development of fidelity measures for the training of service
      providers and treatment delivery is important in specialized treatment approaches
      where certain 'active ingredients' (e.g. specific treatment targets and
      therapeutic techniques) must be present in order for treatment to be effective.
      The PFM reflects evidence-based practice by integrating treatment delivery and
      clinical skill as a single quantifiable metric. PFM enables researchers and
      clinicians to objectively measure treatment outcomes within the PROMPT approach.

PMID- 26213622
TI  - Relationships between self-report and cognitive measures of hearing aid outcome.
AB  - This present study examined the relationship between cognitive measures and self
      report hearing aid outcome. A sentence-final word identification and recall
      (SWIR) test was used to investigate how hearing aid use may relate to experienced
      explicit cognitive processing. A visually based cognitive test battery was also
      administered. To measure self-report hearing aid outcome, the International
      Outcome Inventory - Hearing Aids (IOI-HA) and the Speech, Spatial and Qualities
      of Hearing Scale (SSQ) were employed. Twenty-six experienced hearing aid users
      (mean age of 59 years) with symmetrical moderate-to-moderately severe
      sensorineural hearing loss were recruited. Free recall performance in the SWIR
      test correlated negatively with item 3 of IOI-HA, which measures residual
      difficulty in adverse listening situations. Cognitive abilities related to verbal
      information processing were correlated positively with self-reported hearing aid
      use and overall success. The present study showed that reported residual
      difficulty with hearing aid may relate to experienced explicit processing in
      difficult listening conditions, such that individuals with better cognitive
      capacity tended to report more remaining difficulty in challenging listening
      situations. The possibility of using cognitive measures to predict hearing aid
      outcome in real life should be explored in future research.

PMID- 26213626
TI  - A novel approach to quantifying the spatiotemporal behavior of instrumented grey
      seals used to sample the environment.
AB  - BACKGROUND: Paired with satellite location telemetry, animal-borne instruments
      can collect spatiotemporal data describing the animal's movement and environment
      at a scale relevant to its behavior. Ecologists have developed methods for
      identifying the area(s) used by an animal (e.g., home range) and those used most
      intensely (utilization distribution) based on location data. However, few have
      extended these models beyond their traditional roles as descriptive 2D summaries
      of point data. Here we demonstrate how the home range method, T-LoCoH, can be
      expanded to quantify collective sampling coverage by multiple instrumented
      animals using grey seals (Halichoerus grypus) equipped with GPS tags and acoustic
      transceivers on the Scotian Shelf (Atlantic Canada) as a case study. At the
      individual level, we illustrate how time and space-use metrics quantifying
      individual sampling coverage may be used to determine the rate of acoustic
      transmissions received. RESULTS: Grey seals collectively sampled an area of
      11,308 km (2) and intensely sampled an area of 31 km (2) from June-December. The
      largest area sampled was in July (2094.56 km (2)) and the smallest area sampled
      occurred in August (1259.80 km (2)), with changes in sampling coverage observed
      through time. CONCLUSIONS: T-LoCoH provides an effective means to quantify
      changes in collective sampling effort by multiple instrumented animals and to
      compare these changes across time. We also illustrate how time and space-use
      metrics of individual instrumented seal movement calculated using T-LoCoH can be
      used to account for differences in the amount of time a bioprobe (biological
      sampling platform) spends in an area.

PMID- 26213624
TI  - Biocompatible D-Penicillamine Conjugated Au Nanoparticles: Targeting
      Intracellular Free Copper Ions for Detoxification.
AB  - High thiophillicicity of the Au-nanoparticle (Au NP) surface leads to covalent
      attachment of D-penicillamine molecules to Au NPs to form biocompatible D
      penicillamine conjugated Au NPs. The latter are highly water-dispersible, exhibit
      no cytotoxicity, and can readily penetrate the cell membrane to target
      intracellular free copper ions for selective copper detoxification in the
      presence of the other divalent essential metal ions including Zn(II), Fe(II),
      Mn(II), Ca(II), and Mg(II), thus opening up a new avenue for improving the
      efficacy and pharmacokinetics of D-penicillamine, an important clinical drug
      currently used to treat the copper overload-related diseases and disorders.

PMID- 26213625
TI  - Fast degradable citrate-based bone scaffold promotes spinal fusion.
AB  - It is well known that high rates of fusion failure and pseudoarthrosis
      development (5~35%) are concomitant in spinal fusion surgery, which was ascribed
      to the shortage of suitable materials for bone regeneration. Citrate was recently
      recognized to play an indispensable role in enhancing osteconductivity and
      osteoinductivity, and promoting bone formation. To address the material
      challenges in spinal fusion surgery, we have synthesized mechanically robust and
      fast degrading citrate-based polymers by incorporating N-methyldiethanolamine
      (MDEA) into clickable poly(1, 8-octanediol citrates) (POC-click), referred to as
      POC-M-click. The obtained POC-M-click were fabricated into POC-M-click-HA
      matchstick scaffolds by compositing with hydroxyapatite (HA) for interbody spinal
      fusion in a rabbit model. Spinal fusion was analyzed by radiography, manual
      palpation, biomechanical testing, and histological evaluation. At 4 and 8 weeks
      post surgery, POC-M-click-HA scaffolds presented optimal degradation rates that
      facilitated faster new bone formation and higher spinal fusion rates (11.2+/-3.7,
      80+/-4.5 at week 4 and 8, respectively) than the poly(L-lactic acid)-HA (PLLA-HA)
      control group (9.3+/-2.4 and 71.1+/-4.4) (p<0.05). The POC-M-click-HA scaffold
      fused vertebrates possessed a maximum load and stiffness of 880.8+/-14.5 N and
      843.2+/-22.4 N/mm, respectively, which were also much higher than those of the
      PLLA-HA group (maximum: 712.0+/-37.5 N, stiffness: 622.5+/-28.4 N/mm, p<0.05).
      Overall, the results suggest that POC-M-click-HA scaffolds could potentially
      serve as promising bone grafts for spinal fusion applications.

PMID- 26213628
TI  - Fluoride adsorption on gamma - Fe2O3 nanoparticles.
AB  - BACKGROUND: Fluoride contamination of groundwater, both anthropogenic and
      natural, is a major problem worldwide and hence its removal attracted much
      attention to have clean aquatic systems. In the present work, removal of fluoride
      ions from drinking water tested using synthesized gamma-Fe2O3 nanoparticles.
      METHODS: Nanoparticles were synthesized in co-precipitation method. The prepared
      particles were first characterized by X-ray diffraction (XRD) and Transmission
      Electron Microscope (TEM). Density functional theory (DFT) calculations on
      molecular cluster were used to model infrared (IR) vibrational frequencies and
      inter atomic distances. RESULTS: The average size of the particles was around 5
      nm initially and showed a aggregation upon exposure to the atmosphere for several
      hours giving average particle size of around 5-20 nm. Batch adsorption studies
      were performed for the adsorption of fluoride and the results revealed that gamma
      Fe2O3 nanoparticles posses high efficiency towards adsorption. A rapid adsorption
      occurred during the initial 15 min by removing about 95 +/- 3 % and reached
      equilibrium thereafter. Fluoride adsorption was found to be dependent on the
      aqueous phase pH and the uptake was observed to be greater at lower pH. Fourier
      transform infrared spectroscopy (FT-IR) was used for the identification of
      functional groups responsible for the adsorption and revealed that the direct
      interaction between fluoride and the gamma-Fe2O3 particles. CONCLUSIONS: The
      mechanism for fluoride removal was explained using the dehydoxylation pathway of
      the hydroxyl groups by the incoming fluoride ion. FT-IR data and other results
      from the ionic strength dependence strongly indicated that formation of inner
      spherically bonded complexes. Molecular clusters were found to be good agreement
      with experimental observations. These results show direct chemical interaction
      with fluoride ions.

PMID- 26213629
TI  - French good practice guidelines for medical and occupational surveillance of the
      low back pain risk among workers exposed to manual handling of loads.
AB  - Several clinical practice guidelines related to the assessment and management of
      low back pain (LBP) have been published with varied scopes and methods. This
      paper summarises the first French occupational guidelines for management of work
      related LBP (October 2013). There main originality is to treat all the three
      stages of primary, secondary and tertiary prevention of work-related LBP. The
      guidelines were written by a multidisciplinary working group of 24 experts,
      according to the Clinical Practice Guidelines method proposed by French National
      Health Authority, and reviewed by a multidisciplinary peer review committee of 50
      experts. Recommendations were based on a large systematic review of the
      literature carried out from 1990 to 2012 and rated as strong (Level A), moderate
      (B), limited (C) or based on expert consensus (D) according to their level of
      evidence. It is recommended to deliver reassuring and consistent information
      concerning LBP prognosis (Level B); to perform a clinical examination looking for
      medical signs of severity related to LBP (Level A), encourage continuation or
      resumption of physical activity (Level A), identify any changes in working
      conditions and evaluate the occupational impact of LBP (Level D). In case of
      persistent/recurrent LBP, assess prognostic factors likely to influence
      progression to chronic LBP, prolonged disability and delayed return to work
      (Level A). In case of prolonged/repeated sick leave, evaluate the pain,
      functional disability and their impact and main risk factors for prolonged work
      disability (Level A), promote return to work measures and inter professional
      coordination (Level D). These good practice guidelines are primarily intended for
      professionals of occupational health but also for treating physicians and
      paramedical personnel participating in the management of LBP, workers and
      employers. 

PMID- 26213630
TI  - Children, sealants, and guardians who smoke: Trends in NHANES 2001-2002 to 2010
      2012.
AB  - OBJECTIVE: There are many factors influencing dental behavior. The relationship
      of smokers who smoked inside the home toward preventive care (measured as dental
      sealant placement) of the children living in their homes is examined in this
      study. METHODS: Data from the National Health and Nutrition Examination Surveys
      in 2001-2002 and in 2011-2012 were analyzed. Data included variables to someone
      smoking inside the home, dental sealant placement in children ages 6-less than 20
      years, and sociodemographics which were obtained from a dental examination and a
      home interview. RESULTS: There were 3,352 eligible participants in 2001-2002 and
      2,374 in 2011-2012. The unadjusted odds ratio for not having dental sealants when
      there was someone who smoked inside the home as compared with not having dental
      sealants when there was no one who smoked inside the home was 1.57 (95%CI: 1.17,
      2.10) in 2001-2002. The unadjusted odds ratio was 1.56 (95% CI: 1.20, 2.03) in
      2011-2012. When the data were adjusted for age, sex, race/ethnicity, insurance,
      and income to poverty ratio, the 2001-2002 adjusted odds ratio was 1.31 (95%CI:
      0.97, 1.78). The adjusted odds ratio in 2011-2012 was 1.41 (95% CI:1.01, 1.95).
      CONCLUSIONS: Children who lived in homes in which someone smoked inside the home
      were more likely to not have dental sealants compared with children who lived in
      homes in which no one smoked inside the home. These results are important for
      understanding the factors related to access to dental care issues for children.

PMID- 26213631
TI  - The Impact of Surface Ligands and Synthesis Method on the Toxicity of Glutathione
      Coated Gold Nanoparticles.
AB  - Gold nanoparticles (AuNPs) are increasingly used in biomedical applications,
      hence understanding the processes that affect their biocompatibility and
      stability are of significant interest. In this study, we assessed the stability
      of peptide-capped AuNPs and used the embryonic zebrafish (Danio rerio) as a
      vertebrate system to investigate the impact of synthesis method and purity on
      their biocompatibility. Using glutathione (GSH) as a stabilizer, Au-GSH
      nanoparticles with identical core sizes were terminally modified with Tryptophan
      (Trp), Histidine (His) or Methionine (Met) amino acids and purified by either
      dialysis or ultracentrifugation. Au-GSH-(Trp)2 purified by dialysis elicited
      significant morbidity and mortality at 200 MUg/mL, Au-GSH-(His)2 induced
      morbidity and mortality after purification by either method at 20 and 200 MUg/mL,
      and Au-GSH-(Met)2 caused only sublethal responses at 200 MUg/mL. Overall,
      toxicity was significantly reduced and ligand structure was improved by
      implementing ultracentrifugation purifications at several stages during the multi
      step synthesis and surface modification of Au-GSH nanoparticles. When carefully
      synthesized at high purity, peptide-functionalized AuNPs showed high
      biocompatibility in biological systems.

PMID- 26213627
TI  - Pharmacology and physiology of gastrointestinal enteroendocrine cells.
AB  - Gastrointestinal (GI) polypeptides are secreted from enteroendocrine cells
      (EECs). Recent technical advances and the identification of endogenous and
      synthetic ligands have enabled exploration of the pharmacology and physiology of
      EECs. Enteroendocrine signaling pathways stimulating hormone secretion involve
      multiple nutrient transporters and G protein-coupled receptors (GPCRs), which are
      activated simultaneously under prevailing nutrient conditions in the intestine
      following a meal. The majority of studies investigate hormone secretion from EECs
      in response to single ligands and although the mechanisms behind how individual
      signaling pathways generate a hormonal output have been well characterized, our
      understanding of how these signaling pathways converge to generate a single
      hormone secretory response is still in its infancy. However, a picture is
      beginning to emerge of how nutrients and full, partial, or allosteric GPCR
      ligands differentially regulate the enteroendocrine system and its interaction
      with the enteric and central nervous system. So far, activation of multiple
      pathways underlies drug discovery efforts to harness the therapeutic potential of
      the enteroendocrine system to mimic the phenotypic changes observed in patients
      who have undergone Roux-en-Y gastric surgery. Typically obese patients exhibit
      ~30% weight loss and greater than 80% of obese diabetics show remission of
      diabetes. Targeting combinations of enteroendocrine signaling pathways that work
      synergistically may manifest with significant, differentiated EEC secretory
      efficacy. Furthermore, allosteric modulators with their increased selectivity,
      self-limiting activity, and structural novelty may translate into more promising
      enteroendocrine drugs. Together with the potential to bias enteroendocrine GPCR
      signaling and/or to activate multiple divergent signaling pathways highlights the
      considerable range of therapeutic possibilities available. Here, we review the
      pharmacology and physiology of the EEC system. 

PMID- 26213632
TI  - The dependences of osteocyte network on bone compartment, age, and disease.
AB  - Osteocytes, the most abundant bone cells, form an interconnected network in the
      lacunar-canalicular pore system (LCS) buried within the mineralized matrix, which
      allows osteocytes to obtain nutrients from the blood supply, sense external
      mechanical signals, and communicate among themselves and with other cells on bone
      surfaces. In this study, we examined key features of the LCS network including
      the topological parameter and the detailed structure of individual connections
      and their variations in cortical and cancellous compartments, at different ages,
      and in two disease conditions with altered mechanosensing (perlecan deficiency
      and diabetes). LCS network showed both topological stability, in terms of
      conservation of connectivity among osteocyte lacunae (similar to the "nodes" in a
      computer network), and considerable variability the pericellular annular fluid
      gap surrounding lacunae and canaliculi (similar to the "bandwidth" of individual
      links in a computer network). Age, in the range of our study (15-32 weeks),
      affected only the pericellular fluid annulus in cortical bone but not in
      cancellous bone. Diabetes impacted the spacing of the lacunae, while the perlecan
      deficiency had a profound influence on the pericellular fluid annulus. The LCS
      network features play important roles in osteocyte signaling and regulation of
      bone growth and adaptation.

PMID- 26213633
TI  - Text Messaging Improves Participation in Laboratory Testing in Adolescent Liver
      Transplant Patients.
AB  - BACKGROUND: In solid organ transplant patients, non-participation in all aspects
      of the medical regimen is a prevalent problem associated with adverse
      consequences particularly in the adolescent and young adult (AYA) age group. This
      study is the first to evaluate the feasibility, utility and impact of a text
      messaging (TM) intervention to improve participation in laboratory testing in
      adolescent liver transplant patients. METHODS: AYA patients, aged 12 to 21 years,
      were recruited for a prospective pilot trial evaluating a TM intervention
      delivered over a 1-year period. The intervention involved automated TM reminders
      with feedback administered according to a prescribed laboratory testing
      frequency. Participation rate in laboratory testing after the intervention was
      compared to the year prior. Patient responses and feedback by text and survey
      were used to assess feasibility, acceptability and use of the intervention.
      RESULTS: Forty-two patients were recruited and 33 patients remained enrolled for
      the study duration. Recipients of the TM intervention demonstrated a significant
      improvement in participation rate in laboratory testing from 58% to 78% (P<.001).
      This rate was also significantly higher than in non-intervention controls
      (P=.003). There was a high acceptability, response rate and a significant
      correlation with reported versus actual completion of laboratory tests by TM.
      CONCLUSIONS: TM reminders significantly improved participation in laboratory
      testing in AYA liver transplant patients. The intervention demonstrated
      feasibility, acceptability, and use with a high proportion of patients who
      engaged in and perceived a benefit from using this technology.

PMID- 26213634
TI  - Reactive Oxygen Species and Nuclear Factor Erythroid 2-Related Factor 2
      Activation in Diabetic Nephropathy: A Hidden Target.
AB  - Hyperglycemia, oxidative stress and renin-angiotensin system (RAS) dysfunction
      have been implicated in diabetic nephropathy (DN) progression, but the underlying
      molecular mechanisms are far from being fully understood. In addition to the
      systemic RAS, the existence of a local intrarenal RAS in renal proximal tubular
      cells has been recognized. Angiotensinogen is the sole precursor of all
      angiotensins (Ang). Intrarenal reactive oxygen species (ROS) generation, Ang II
      level and RAS gene expression are up-regulated in diabetes, indicating that
      intrarenal ROS and RAS activation play an important role in DN. The nuclear
      factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1
      (Keap1) pathway is one of the major protective processes that occurs in response
      to intracellular oxidative stress. Nrf2 stimulates an array of antioxidant
      enzymes that convert excessive ROS to less reactive or less damaging forms.
      Recent studies have, however, revealed that Nrf2 activation might have other
      undesirable effects in diabetic animals and in diabetic patients with chronic
      kidney disease. This mini-review summarizes current knowledge of the relationship
      between ROS, Nrf2 and intra renal RAS activation in DN progression as well as
      possible novel target(s) for DN treatment.

PMID- 26213635
TI  - Macrophage Polarization in Virus-Host Interactions.
AB  - Macrophage involvement in viral infections and antiviral states is common.
      However, this involvement has not been well-studied in the paradigm of macrophage
      polarization, which typically has been categorized by the dichotomy of classical
      (M1) and alternative (M2) statuses. Recent studies have revealed the complexity
      of macrophage polarization in response to various cellular mediators and
      exogenous stimuli by adopting a multipolar view to revisit the differential
      process of macrophages, especially those re-polarized during viral infections.
      Here, through examination of viral infections targeting macrophages/monocytic
      cells, we focus on the direct involvement of macrophage polarization during viral
      infections. Type I and type III interferons (IFNs) are critical in regulation of
      viral pathogenesis and host antiviral infection; thus, we propose to incorporate
      IFN-mediated antiviral states into the framework of macrophage polarization. This
      view is supported by the multifunctional properties of type I IFNs, which
      potentially elicit and regulate both M1- and M2-polarization in addition to
      inducing the antiviral state, and by the discoveries of viral mechanisms to adapt
      and modulate macrophage polarization. Indeed, several recent studies have
      demonstrated effective prevention of viral diseases through manipulation of
      macrophage immune statuses.

PMID- 26213488
TI  - Constraints on the off-shell Higgs boson signal strength in the high-mass ZZ and
      WW final states with the ATLAS detector.
AB  - Measurements of the ZZ and WW final states in the mass range above the [Formula:
      see text] and [Formula: see text] thresholds provide a unique opportunity to
      measure the off-shell coupling strength of the Higgs boson. This paper presents
      constraints on the off-shell Higgs boson event yields normalised to the Standard
      Model prediction (signal strength) in the [Formula: see text], [Formula: see
      text] and [Formula: see text] final states. The result is based on pp collision
      data collected by the ATLAS experiment at the LHC, corresponding to an integrated
      luminosity of 20.3 fb[Formula: see text] at a collision energy of [Formula: see
      text] TeV. Using the [Formula: see text] method, the observed 95 [Formula: see
      text] confidence level (CL) upper limit on the off-shell signal strength is in
      the range 5.1-8.6, with an expected range of 6.7-11.0. In each case the range is
      determined by varying the unknown [Formula: see text] and [Formula: see text]
      background K-factor from higher-order quantum chromodynamics corrections between
      half and twice the value of the known signal K-factor. Assuming the relevant
      Higgs boson couplings are independent of the energy scale of the Higgs boson
      production, a combination with the on-shell measurements yields an observed
      (expected) 95 [Formula: see text] CL upper limit on [Formula: see text] in the
      range 4.5-7.5 (6.5-11.2) using the same variations of the background K-factor.
      Assuming that the unknown [Formula: see text] background K-factor is equal to the
      signal K-factor, this translates into an observed (expected) 95 [Formula: see
      text] CL upper limit on the Higgs boson total width of 22.7 (33.0) MeV.

PMID- 26213636
TI  - STAT1 is Constitutively Activated in the T/C28a2 Immortalized Juvenile Human
      Chondrocyte Line and Stimulated by IL-6 Plus Soluble IL-6R.
AB  - T/C28a2 immortalized juvenile human chondrocytes were employed to determine the
      extent to which activation of Signal Transducers and Activators of Transcription
      1 (STAT1) occurred in response to recombinant human interleukin-6 (rhIL-6) or
      rhIL-6 in combination with the soluble IL-6 receptor (sIL-6R). Two forms of
      STAT1, STAT1A and STAT1B, were identified on SDS-PAGE and western blotting with
      anti-STAT1 antibody. Western blotting revealed that STAT1 was constitutively
      phosphorylated (p-STAT1). Although incubation of T/C28a2 chondrocytes with rhIL-6
      (50 ng/ml) increased p-STAT1A by Delta=22.3% after 30 min, this percent
      difference failed to reach significance by Chi-square analysis. Similarly, no
      effect of rhIL-6 (Delta=+10.7%) on p-STAT1B was seen at 30 min. In contrast,
      although the combination of rhIL-6 plus sIL-6R had no effect on p-STAT1A, rhIL-6
      plus sIL-6R increased p-STAT1B by Delta=73.3% (p<0.0001) after 30 min compared to
      the control group and by Delta=56.7% (p<0.0001) compared to rhIL-6 alone. Janex
      1, a Janus kinase-3-specific inhibitor (100 MUM) partially reduced the effect of
      rhIL-6 on p-STAT1B by Delta=27.7% (p<0.05). The results of this study showed that
      STAT1A/STAT1B was constitutively activated in T/C28a2 chondrocytes. Although rhIL
      6 increased p-STAT1B to a small extent, the combination of rhIL-6 plus sIL-6R was
      far more effective in stimulating STAT1B phosphorylation compared to controls or
      rhIL-6 alone. These data support the likelihood that although JAK3-mediated
      activation of STAT1 in T/C28a2 chondrocytes may involve the IL-6/IL-6R/gp130
      pathway, these results indicated that STAT1 activation in response to IL-6
      preferentially involved IL-6 trans-signaling via sIL-6R.

PMID- 26213637
TI  - Women's Empowerment and Microcredit: A Case Study from Rural Ghana.

PMID- 26213639
TI  - Quantifying selective pressures driving bacterial evolution using lineage
      analysis.
AB  - Organisms use a variety of strategies to adapt to their environments and maximize
      long-term growth potential, but quantitative characterization of the benefits
      conferred by the use of such strategies, as well as their impact on the whole
      population's rate of growth, remains challenging. Here, we use a path-integral
      framework that describes how selection acts on lineages -i.e. the life-histories
      of individuals and their ancestors- to demonstrate that lineage-based
      measurements can be used to quantify the selective pressures acting on a
      population. We apply this analysis to E. coli bacteria exposed to cyclical
      treatments of carbenicillin, an antibiotic that interferes with cell-wall
      synthesis and affects cells in an age-dependent manner. While the extensive
      characterization of the life-history of thousands of cells is necessary to
      accurately extract the age-dependent selective pressures caused by carbenicillin,
      the same measurement can be recapitulated using lineage-based statistics of a
      single surviving cell. Population-wide evolutionary pressures can be extracted
      from the properties of the surviving lineages within a population, providing an
      alternative and efficient procedure to quantify the evolutionary forces acting on
      a population. Importantly, this approach is not limited to age-dependent
      selection, and the framework can be generalized to detect signatures of other
      trait-specific selection using lineage-based measurements. Our results establish
      a powerful way to study the evolutionary dynamics of life under selection, and
      may be broadly useful in elucidating selective pressures driving the emergence of
      antibiotic resistance and the evolution of survival strategies in biological
      systems.

PMID- 26213641
TI  - "Bare Branches" and the Marriage Market in Rural China: Preliminary Evidence from
      a village-level survey.
AB  - Using data from a village survey in rural China, this study explores the
      relationships between current prevalence of involuntary bachelorhood and its
      causes and social consequences at the village level. We find that bachelors,
      inter-county marriage and marriage fraud exist in all regions, and are expected
      to become more frequent with the increasing surplus of males born after 1980
      entering the marriage market. The marriage squeeze and social problems related to
      the bachelors are more serious in less-developed western villages, and
      heterogeneity within central villages is significant. Economic and socio
      demographic factors are shown to be the major causes of the prevalence of
      bachelors at the village level in contemporary rural China. Our findings confirm
      the negative consequences of the marriage squeeze, and effective policies are
      urgently needed to respond to and prevent more negative consequences of gender
      imbalance in the foreseeable future.

PMID- 26213638
TI  - Use of ChemoFx(r) for Identification of Effective Treatments in Epithelial
      Ovarian Cancer.
AB  - Selection of appropriate chemotherapy, including identification of platinum
      resistance, is critical to effective management of advanced epithelial ovarian
      cancer (EOC). ChemoFx(r), a multiple treatment marker (chemoresponse assay), has
      been developed to address this challenge and to improve outcomes in patients with
      advanced EOC. While much work has been done that has demonstrated the analytical
      validity of this assay, more recent studies have highlighted the unique clinical
      benefits offered by the assay. A prospective, multicenter trial has shown an
      increase in overall survival (OS) of 14 months and an increase in progression
      free survival (PFS) by 3 months in patients with recurrent EOS treated by a
      "sensitive" therapy based on ChemoFx results. Along with other studies showing
      similar gains in OS and PFS, ChemoFx has been shown to be both a prognostic and
      predictive marker in patients with recurrent EOC where current treatment options
      are sorely lacking. In addition to these clinical benefits, economic analyses
      have shown that ChemoFx is a cost-effective intervention. Current guidelines and
      technology assessments relating to ChemoFx are largely outdated and refer
      primarily to metrics of analytical validity. Thus, in addition to analytical
      validity, the clinical validity, clinical utility and economic impact of ChemoFx
      are reviewed herein, including published literature, technology assessments by
      independent parties, and regulatory approvals of this marker. 

PMID- 26213640
TI  - Caloric restriction for treatment of geriatric obesity: Do the benefits outweigh
      the risks?
AB  - Most evidence for the health benefits of prescribing caloric restriction (CR) for
      weight loss is derived from randomized, controlled trials (RCTs) in young/middle
      aged adults; there are very few RCTs in older adults in which the isolated
      effects of CR can be deciphered. The purpose of this review is to summarize the
      RCT evidence of the benefits (and potential risks) of CR for the treatment of
      obesity in older adults. We identified only 19 published papers from 10 RCTs
      ranging from 3 to 18 months that met the criteria of independent effects of a CR
      component and were conducted in adults with a mean age >=65 yrs. Overall, the
      results show a beneficial treatment effect for improving some metabolic,
      functional and body composition outcomes with few documented risks. However, all
      outcomes were assessed immediately after treatment cessation. Thus, until
      additional scientifically rigorous evidence with long-term follow-up is
      available, the risk-to-benefit ratio of CR for the treatment of obesity in older
      adults remains unclear.

PMID- 26213642
TI  - Vascular Dementia.
AB  - The purpose of this review is to highlight existing literature on the
      epidemiology, pathophysiology, and novel risk factors for vascular dementia. We
      further examine the evidence linking chronic brain hypoperfusion induced by a
      variety of cardiovascular diseases to the development of vascular dementia. In
      the elderly, in whom cerebral perfusion is diminished by the aging process,
      additional reduction in cerebral blood flow stemming from exposure to potentially
      modifiable vascular risk factors increases the probability of developing vascular
      dementia. Finally, we discuss the association between obstructive sleep apnea, an
      underrecognized risk factor for stroke, and vascular dementia. Obstructive sleep
      apnea is linked to cerebrovascular disease through many intermediary vascular
      risk factors and may directly cause cerebrovascular damage through microvacular
      disease. Insight into how cardiovascular risk factors induce vascular dementia
      offers an enhanced understanding of the multifactorial pathophysiology by this
      disorder and ways of preventing and managing the cerebrovascular precursors of
      vascular dementia. Many vital questions about the relation of obstructive sleep
      apnea with stroke and vascular dementia are still unanswered and await future
      well-designed studies.

PMID- 26213645
TI  - Detecting When "Quality of Life" Has Been "Enhanced": Estimating Change in
      Quality of Life Ratings.
AB  - OBJECTIVE: To demonstrate challenges in the estimation of change in quality of
      life (QOL). METHODS: Data were taken from a completed clinical trial with
      negative results. Responses to 13 QOL items were obtained 12 months apart from
      258 persons with Alzheimer's disease (AD) participating in a randomized, placebo
      controlled clinical trial with two treatment arms. Two analyses to estimate
      whether "change" in QOL occurred over 12 months are described. A simple
      difference (later - earlier) was calculated from total scores (standard
      approach). A Qualified Change algorithm (novel approach) was applied to each
      item: differences in ratings were classified as either: improved, worsened,
      stayed poor, or stayed "positive" (fair, good, excellent). The strengths of
      evidence supporting a claim that "QOL changed", derived from the two analyses,
      were compared by considering plausible alternative explanations for, and
      interpretations of, results obtained under each approach. RESULTS: Total score
      approach: QOL total scores decreased, on average, in the two treatment (both 
      1.0, p < 0.05), but not the placebo (=-0.59, p > 0.3) groups. Qualified change
      approach: Roughly 60% of all change in QOL items was worsening in every arm; 17% 
      42% of all subjects experienced change in each item. CONCLUSIONS: Totalling the
      subjective QOL item ratings collapses over items, and suggests a potentially
      misleading "overall" level of change (or no change, as in the placebo arm).
      Leaving the items as individual components of "quality" of life they were
      intended to capture, and qualifying the direction and amount of change in each,
      suggests that at least 17% of any group experienced change on every item, with
      60% of all observed change being worsening. DISCUSSION: Summarizing QOL item
      ratings as a total "score" collapses over the face-valid, multi-dimensional
      components of the construct "quality of life". Qualified Change provides robust
      evidence of changes to QOL or "enhancements of" life quality.

PMID- 26213644
TI  - Social Relationships and Obesity: Benefits of Incorporating a Lifecourse
      Perspective.
AB  - Social networks reflect the structure of our interpersonal relationships. The
      effect of social networks on health is a topic of growing interest, particularly
      in an increasingly connected world. This review provides an overview of how
      social relations shape obesity risk and the effectiveness of network-based
      obesity interventions across the life course. The review highlights that, while
      the literature suggests obesity and related health behaviors are similar between
      socially-connected individuals, why this is the case and how to effectively
      intervene remains unclear. In addition, the review outlines methodological gaps
      limiting our understanding of how social networks shape obesity risk throughout
      the lifecourse. Several implications for obesity prevention and research are
      offered, including the need to examine the relationship of social networks and
      obesity across rather than within life-course stages, continued development of
      statistical social network analysis methods and the need for new cohort studies,
      particularly among children and the elderly. 

PMID- 26213643
TI  - A Review of Primary Care-Based Childhood Obesity Prevention and Treatment
      Interventions.
AB  - Effective obesity prevention and treatment interventions targeting children and
      their families are needed to help curb the obesity epidemic. Pediatric primary
      care is a promising setting for these interventions, and a growing number of
      studies are set in this context. This review aims to identify randomized
      controlled trials of pediatric primary care-based obesity interventions. A
      literature search of 3 databases retrieved 2947 publications, of which 2899
      publications were excluded after abstract (n=2722) and full-text review (n=177).
      Forty-eight publications, representing 31 studies, were included in the review.
      Eight studies demonstrated a significant intervention effect on child weight
      outcomes (e.g., BMI z-score, weight-for-length percentile). Effective
      interventions were mainly treatment interventions, and tended to focus on
      multiple behaviors, contain weight management components, and include monitoring
      of weight-related behaviors (e.g., dietary intake, physical activity, or
      sedentary behaviors). Overall, results demonstrate modest support for the
      efficacy of obesity treatment interventions set in primary care. 

PMID- 26213646
TI  - Relative availability of natural prey versus livestock predicts landscape
      suitability for cheetahs Acinonyx jubatus in Botswana.
AB  - Prey availability and human-carnivore conflict are strong determinants that
      govern the spatial distribution and abundance of large carnivore species and
      determine the suitability of areas for their conservation. For wide-ranging large
      carnivores such as cheetahs (Acinonyx jubatus), additional conservation areas
      beyond protected area boundaries are crucial to effectively conserve them both
      inside and outside protected areas. Although cheetahs prefer preying on wild
      prey, they also cause conflict with people by predating on especially small
      livestock. We investigated whether the distribution of cheetahs' preferred prey
      and small livestock biomass could be used to explore the potential suitability of
      agricultural areas in Botswana for the long-term persistence of its cheetah
      population. We found it gave a good point of departure for identifying priority
      areas for land management, the threat to connectivity between cheetah
      populations, and areas where the reduction and mitigation of human-cheetah
      conflict is critical. Our analysis showed the existence of a wide prey base for
      cheetahs across large parts of Botswana's agricultural areas, which provide
      additional large areas with high conservation potential. Twenty percent of wild
      prey biomass appears to be the critical point to distinguish between high and low
      probable levels of human-cheetah conflict. We identified focal areas in the
      agricultural zones where restoring wild prey numbers in concurrence with
      effective human-cheetah conflict mitigation efforts are the most immediate
      conservation strategies needed to maintain Botswana's still large and contiguous
      cheetah population. 

PMID- 26213647
TI  - Photos provide information on age, but not kinship, of Andean bear.
AB  - Using photos of captive Andean bears of known age and pedigree, and photos of
      wild Andean bear cubs <6 months old, we evaluated the degree to which visual
      information may be used to estimate bears' ages and assess their kinship. We
      demonstrate that the ages of Andean bear cubs <=6 months old may be estimated
      from their size relative to their mothers with an average error of <0.01 +/- 13.2
      days (SD; n = 14), and that ages of adults >=10 years old may be estimated from
      the proportion of their nose that is pink with an average error of <0.01 +/- 3.5
      years (n = 41). We also show that similarity among the bears' natural markings,
      as perceived by humans, is not associated with pedigree kinship among the bears
      (R (2) < 0.001, N = 1,043, p = 0.499). Thus, researchers may use photos of wild
      Andean bears to estimate the ages of young cubs and older adults, but not to
      infer their kinship. Given that camera trap photos are one of the most readily
      available sources of information on large cryptic mammals, we suggest that
      similar methods be tested for use in other poorly understood species. 

PMID- 26213489
TI  - Search for invisible decays of the Higgs boson produced in association with a
      hadronically decaying vector boson in pp collisions at [Formula: see text] TeV
      with the ATLAS detector.
AB  - A search for Higgs boson decays to invisible particles is performed using 20.3
      [Formula: see text] of pp collision data at a centre-of-mass energy of 8 TeV
      recorded by the ATLAS detector at the Large Hadron Collider. The process
      considered is Higgs boson production in association with a vector boson
      ([Formula: see text] or Z) that decays hadronically, resulting in events with two
      or more jets and large missing transverse momentum. No excess of candidates is
      observed in the data over the background expectation. The results are used to
      constrain VH production followed by H decaying to invisible particles for the
      Higgs boson mass range [Formula: see text] GeV. The 95 % confidence-level
      observed upper limit on [Formula: see text] varies from 1.6 pb at 115 GeV to 0.13
      pb at 300 GeV. Assuming Standard Model production and including the [Formula: see
      text] contribution as signal, the results also lead to an observed upper limit of
      78 % at 95 % confidence level on the branching ratio of Higgs bosons decays to
      invisible particles at a mass of 125 GeV.

PMID- 26213648
TI  - The seasonal reproduction number of dengue fever: impacts of climate on
      transmission.
AB  - Background. Dengue fever is a mosquito-borne viral disease and a regular epidemic
      in Thailand. The peak of the dengue epidemic period is around June to August
      during the rainy season. It is believed that climate is an important factor for
      dengue transmission. Method. A mathematical model for vector-host infectious
      disease was used to calculate the impacts of climate to the transmission of
      dengue virus. In this study, the data of climate and dengue fever cases were
      derived from Chiang Mai during 2004-2014, Thailand. The value of seasonal
      reproduction number was calculated to evaluate the potential, severity and
      persistence of dengue infection. Results. The mosquito population was increasing
      exponentially from the start of the rainy season in early May and reached its the
      peak in late June. The simulations suggest that the greatest potential for the
      dengue transmission occurs when the temperature is 28.9  degrees C. The seasonal
      reproduction numbers were larger than one from late March to end of August and
      reaching the peak in June. The highest incidences occurred in August due to the
      delay of transmission humans-mosquito-humans. Increasing mean temperature by 1 
      degrees C, the number of incidences increases 28.1%. However, a very high or very
      low temperature reduces the number of infection. Discussion and Conclusion. The
      results show that the dengue infection depends on the seasonal variation of the
      climate. The rainfall provides places for the mosquitoes to lay eggs and develop
      to the adult stage. The temperature plays an important role in the life cycle and
      behavior of the mosquitoes. A very high or very low temperature reduces the risk
      of the dengue infection. 

PMID- 26213656
TI  - Do the effects of crops on skylark (Alauda arvensis) differ between the field and
      landscape scales?
AB  - The promotion of biodiversity in agricultural areas involves actions at the
      landscape scale, and the management of cropping patterns is considered an
      important means of achieving this goal. However, most of the available knowledge
      about the impact of crops on biodiversity has been obtained at the field scale,
      and is generally grouped together under the umbrella term "crop suitability." Can
      field-scale knowledge be used to predict the impact on populations across
      landscapes? We studied the impact of maize and rapeseed on the abundance of
      skylark (Alauda arvensis). Field-scale studies in Western Europe have reported
      diverse impacts on habitat selection and demography. We assessed the consistency
      between field-scale knowledge and landscape-scale observations, using high
      resolution databases describing crops and other habitats for the 4 km(2) grid
      scales analyzed in the French Breeding Bird Survey. We used generalized linear
      models to estimate the impact of each studied crop at the landscape scale. We
      stratified the squares according to the local and geographical contexts, to
      ensure that the conclusions drawn were valid in a wide range of contexts. Our
      results were not consistent with field knowledge for rapeseed, and were
      consistent for maize only in grassland contexts. However, the effect sizes were
      much smaller than those of structural landscape features. These results suggest
      that upscaling from the field scale to the landscape scale leads to an
      integration of new agronomic and ecological processes, making the objects studied
      more complex than simple "crop * species" pairs. We conclude that the carrying
      capacity of agricultural landscapes cannot be deduced from the suitability of
      their components. 

PMID- 26213653
TI  - Taxonomic identification of Lower Pleistocene fossil hominins based on distal
      humeral diaphyseal cross-sectional shape.
AB  - The coexistence of multiple hominin species during the Lower Pleistocene has long
      presented a challenge for taxonomic attribution of isolated postcrania. Although
      fossil humeri are well-suited for studies of hominin postcranial variation due to
      their relative abundance, humeral articular morphology has thus far been of
      limited value for differentiating Paranthropus from Homo. On the other hand,
      distal humeral diaphyseal shape has been used to justify such generic
      distinctions at Swartkrans. The potential utility of humeral diaphyseal shape
      merits larger-scale quantitative analysis, particularly as it permits the
      inclusion of fragmentary specimens lacking articular morphology. This study
      analyzes shape variation of the distal humeral diaphysis among fossil hominins
      (c. 2-1 Ma) to test the hypothesis that specimens can be divided into distinct
      morphotypes. Coordinate landmarks were placed on 3D laser scans to quantify cross
      sectional shape at a standardized location of the humeral diaphysis (proximal to
      the olecranon fossa) for a variety of fossil hominins and extant hominids. The
      fossil sample includes specimens attributed to species based on associated
      craniodental remains. Mantel tests of matrix correlation were used to assess
      hypotheses about morphometric relationships among the fossils by comparing
      empirically-derived Procrustes distance matrices to hypothetical model matrices.
      Diaphyseal shape variation is consistent with the hypothesis of three distinct
      morphotypes (Paranthropus, Homo erectus, non-erectus early Homo) in both eastern
      and southern Africa during the observed time period. Specimens attributed to non
      erectus early Homo are unique among hominids with respect to the degree of
      relative anteroposterior flattening, while H. erectus humeri exhibit morphology
      more similar to that of modern humans. In both geographic regions, Paranthropus
      is characterized by a morphology that is intermediate with respect to those
      morphological features that differentiate the two forms of early Homo. This study
      demonstrates the utility of the humeral diaphysis for taxonomic identification of
      isolated postcranial remains and further documents a high degree of postcranial
      diversity in early Homo. 

PMID- 26213655
TI  - Retrodeformation and muscular reconstruction of ornithomimosaurian dinosaur
      crania.
AB  - Ornithomimosaur dinosaurs evolved lightweight, edentulous skulls that possessed
      keratinous rhamphothecae. Understanding the anatomy of these taxa allows for a
      greater understanding of "ostrich-mimic" dinosaurs and character change during
      theropod dinosaur evolution. However, taphonomic processes during fossilisation
      often distort fossil remains. Retrodeformation offers a means by which to recover
      a hypothesis of the original anatomy of the specimen, and 3D scanning
      technologies present a way to constrain and document the retrodeformation
      process. Using computed tomography (CT) scan data, specimen specific
      retrodeformations were performed on three-dimensionally preserved but
      taphonomically distorted skulls of the deinocheirid Garudimimus brevipesBarsbold,
      1981 and the ornithomimids Struthiomimus altusLambe, 1902 and Ornithomimus
      edmontonicusSternberg, 1933. This allowed for a reconstruction of the adductor
      musculature, which was then mapped onto the crania, from which muscle mechanical
      advantage and bite forces were calculated pre- and post-retrodeformation. The
      extent of the rhamphotheca was varied in each taxon to represent morphologies
      found within modern Aves. Well constrained retrodeformation allows for increased
      confidence in anatomical and functional analysis of fossil specimens and offers
      an opportunity to more fully understand the soft tissue anatomy of extinct taxa. 

PMID- 26213649
TI  - Allele specific expression in worker reproduction genes in the bumblebee Bombus
      terrestris.
AB  - Methylation has previously been associated with allele specific expression in
      ants. Recently, we found methylation is important in worker reproduction in the
      bumblebee Bombus terrestris. Here we searched for allele specific expression in
      twelve genes associated with worker reproduction in bees. We found allele
      specific expression in Ecdysone 20 monooxygenase and IMP-L2-like. Although we
      were unable to confirm a genetic or epigenetic cause for this allele specific
      expression, the expression patterns of the two genes match those predicted for
      imprinted genes. 

PMID- 26213652
TI  - Influence of a hyperlipidic diet on the composition of the non-membrane lipid
      pool of red blood cells of male and female rats.
AB  - Background and objectives. Red blood cells (RBC) are continuously exposed to
      oxidative agents, affecting their membrane lipid function. However, the amount of
      lipid in RBCs is higher than the lipids of the cell membrane, and includes
      triacylglycerols, which are no membrane components. We assumed that the extra
      lipids originated from lipoproteins attached to the cell surface, and we intended
      to analyse whether the size and composition of this lipid pool were affected by
      sex or diet. Experimental design. Adult male and female Wistar rats were fed
      control or cafeteria diets. Packed blood cells and plasma lipids were extracted
      and analysed for fatty acids by methylation and GC-MS, taking care of not
      extracting membrane lipids. Results. The absence of omega3-PUFA in RBC extracts
      (but not in plasma) suggest that the lipids extracted were essentially those in
      the postulated lipid surface pool and not those in cell membrane. In cells'
      extracts, there was a marked depletion of PUFA (and, in general, of
      insaturation). Fatty acid patterns were similar for all groups studied, with
      limited effects of sex and no effects of diet in RBC (but not in plasma) fatty
      acids. Presence of trans fatty acids was small but higher in RBC lipids, and
      could not be justified by dietary sources. Conclusions. The presence of a small
      layer of lipid on the RBC surface may limit oxidative damage to the cell outer
      structures, and help explain its role in the transport of lipophilic compounds.
      However, there may be other, so far uncovered, additional functions for this
      lipid pool. 

PMID- 26213654
TI  - Competitive interactions between a nonmycorrhizal invasive plant, Alliaria
      petiolata, and a suite of mycorrhizal grassland, old field, and forest species.
AB  - The widespread invasion of the nonmycorrhizal biennial plant, Alliaria petiolata
      in North America is hypothesized to be facilitated by the production of novel
      biochemical weapons that suppress the growth of mycorrhizal fungi. As a result,
      A. petiolata is expected to be a strong competitor against plant species that
      rely on mycorrhizal fungi for nutrient uptake services. If A. petiolata is also a
      strong competitor for soil resources, it should deplete nutrients to levels lower
      than can be tolerated by weaker competitors. Because the negative effect of
      losing the fungal symbiont for mycorrhizal plants is greatest when nutrients are
      low, the ability of A. petiolata to simultaneously suppress fungi and efficiently
      take up soil nutrients should further strengthen its competitive ability against
      mycorrhizal plants. To test this hypothesis, we grew 27 mycorrhizal tree, forb
      and grass species that are representative of invaded habitats in the absence or
      presence of competition with A. petiolata in soils that had previously been
      experimentally planted with the invader or left as a control. A history of A.
      petiolata in soil reduced plant available forms of nitrogen by >50% and
      phosphorus by 17% relative to control soil. Average mycorrhizal colonization of
      competitor species was reduced by >50% in A. petiolata history versus control
      soil. Contrary to expectations, competition between A. petiolata and other
      species was stronger in control than history soil. The invader suppressed the
      biomass of 70% of competitor species in control soil but only 26% of species in
      history soil. In addition, A. petiolata biomass was reduced by 56% in history
      versus control soil, whereas the average biomass of competitor species was
      reduced by 15%. Thus, our results suggest that the negative effect of nutrient
      depletion on A. petiolata was stronger than the negative effect of suppressing
      mycorrhizal colonization on competitor species. These findings indicate that the
      inhibitory potential of A. petiolata on competitor species via mycorrhizal
      suppression is not enhanced under nutrient limitation. 

PMID- 26213651
TI  - Urinary microRNA can be concentrated, dried on membranes and stored at room
      temperature in vacuum bags.
AB  - Urine accumulates traces of changes that occur in the body and can potentially
      serve as a better biomarker source. Urinary microRNA is a promising class of non
      invasive disease biomarkers. However, long-term frozen human urine samples are
      not a good source for the extraction of urinary microRNA. In this paper, we
      demonstrate that urinary microRNA can be concentrated, dried on membranes and
      stored in vacuum bags at room temperature for several months. The amount of total
      RNA on the membranes after storage at room temperature for three months was
      unchanged. The levels of miR-16 and miR-21 exhibited no significant differences
      (P = 0.564, 0.386). This simple and economical method makes the large-scale
      storage of clinical samples of urinary microRNA or other nucleic acids possible. 

PMID- 26213650
TI  - Using signals associated with safety in avoidance learning: computational model
      of sex differences.
AB  - Avoidance behavior involves learning responses that prevent upcoming aversive
      events; these responses typically extinguish when the aversive events stop
      materializing. Stimuli that signal safety from aversive events can paradoxically
      inhibit extinction of avoidance behavior. In animals, males and females process
      safety signals differently. These differences help explain why women are more
      likely to be diagnosed with an anxiety disorder and exhibit differences in
      symptom presentation and course compared to men. In the current study, we extend
      an existing model of strain differences in avoidance behavior to simulate sex
      differences in rats. The model successfully replicates data showing that the
      omission of a signal associated with a period of safety can facilitate extinction
      in females, but not males, and makes novel predictions that this effect should
      depend on the duration of the period, the duration of the signal itself, and its
      occurrence within that period. Non-reinforced responses during the safe period
      were also found to be important in the expression of these patterns. The model
      also allowed us to explore underlying mechanisms for the observed sex effects,
      such as whether safety signals serve as occasion setters for aversive events, to
      determine why removing them can facilitate extinction of avoidance. The
      simulation results argue against this account, and instead suggest the signal may
      serve as a conditioned reinforcer of avoidance behavior. 

PMID- 26213657
TI  - Marked increase in rat red blood cell membrane protein glycosylation by one-month
      treatment with a cafeteria diet.
AB  - Background and Objectives. Glucose, an aldose, spontaneously reacts with protein
      amino acids yielding glycosylated proteins. The compounds may reorganize to
      produce advanced glycosylation products, which regulatory importance is
      increasingly being recognized. Protein glycosylation is produced without the
      direct intervention of enzymes and results in the loss of function. Glycosylated
      plasma albumin, and glycosylated haemoglobin are currently used as index of mean
      plasma glucose levels, since higher glucose availability results in higher
      glycosylation rates. In this study we intended to detect the early changes in
      blood protein glycosylation elicited by an obesogenic diet. Experimental Design.
      Since albumin is in constant direct contact with plasma glucose, as are the red
      blood cell (RBC) membranes, we analyzed their degree or glycosylation in female
      and male rats, either fed a standard diet or subjected to a hyper-energetic self
      selected cafeteria diet for 30 days. This model produces a small increase in
      basal glycaemia and a significant increase in body fat, leaving the animals in
      the initial stages of development of metabolic syndrome. We also measured the
      degree of glycosylation of hemoglobin, and the concentration of glucose in
      contact with this protein, that within the RBC. Glycosylation was measured by
      colorimetric estimation of the hydroxymethylfurfural liberated from glycosyl
      residues by incubation with oxalate. Results. Plasma glucose was higher in
      cafeteria diet and in male rats, both independent effects. However, there were no
      significant differences induced by sex or diet in either hemoglobin or plasma
      proteins. Purified RBC membranes showed a marked effect of diet: higher
      glycosylation in cafeteria rats, which was more marked in females (not in
      controls). In any case, the number of glycosyl residues per molecule were higher
      in hemoglobin than in plasma proteins (after correction for molecular weight).
      The detected levels of glucose in RBC were lower than those of plasma, even when
      expressed in molal units, and were practically nil in cafeteria-diet fed rats
      compared with controls; there was no effect of sex. Conclusions. RBC membrane
      glycosylation is a sensitive indicator of developing metabolic syndrome-related
      hyperglycemia, more sensitive than the general measurement of plasma or RBC
      protein glycosylation. The extensive glycosylation of blood proteins does not
      seem to be markedly affected by sex; and could be hardly justified from an
      assumedly sustained plasma hyperglycemia. The low levels of glucose found within
      RBC, especially in rats under the cafeteria diet, could hardly justify the
      extensive glycosylation of hemoglobin and the lack of differences with controls,
      which contained sizeable levels of intracellular glucose. Additional studies are
      needed to study the dynamics of glucose in vivo in the RBC to understand how such
      extensive protein glycosylation could take place. 

PMID- 26213658
TI  - MetaBoot: a machine learning framework of taxonomical biomarker discovery for
      different microbial communities based on metagenomic data.
AB  - As more than 90% of species in a microbial community could not be isolated and
      cultivated, the metagenomic methods have become one of the most important methods
      to analyze microbial community as a whole. With the fast accumulation of
      metagenomic samples and the advance of next-generation sequencing techniques, it
      is now possible to qualitatively and quantitatively assess all taxa (features) in
      a microbial community. A set of taxa with presence/absence or their different
      abundances could potentially be used as taxonomical biomarkers for identification
      of the corresponding microbial community's phenotype. Though there exist some
      bioinformatics methods for metagenomic biomarker discovery, current methods are
      not robust, accurate and fast enough at selection of non-redundant biomarkers for
      prediction of microbial community's phenotype. In this study, we have proposed a
      novel method, MetaBoot, that combines the techniques of mRMR (minimal redundancy
      maximal relevance) and bootstrapping, for discover of non-redundant biomarkers
      for microbial communities through mining of metagenomic data. MetaBoot has been
      tested and compared with other methods on well-designed simulated datasets
      considering normal and gamma distribution as well as publicly available
      metagenomic datasets. Results have shown that MetaBoot was robust across datasets
      of varied complexity and taxonomical distribution patterns and could also select
      discriminative biomarkers with quite high accuracy and biological consistency.
      Thus, MetaBoot is suitable for robustly and accurately discover taxonomical
      biomarkers for different microbial communities. 

PMID- 26213659
TI  - Dysphagia Screening: Contributions of Cervical Auscultation Signals and Modern
      Signal-Processing Techniques.
AB  - Cervical auscultation is the recording of sounds and vibrations caused by the
      human body from the throat during swallowing. While traditionally done by a
      trained clinician with a stethoscope, much work has been put towards developing
      more sensitive and clinically useful methods to characterize the data obtained
      with this technique. The eventual goal of the field is to improve the
      effectiveness of screening algorithms designed to predict the risk that
      swallowing disorders pose to individual patients' health and safety. This paper
      provides an overview of these signal processing techniques and summarizes recent
      advances made with digital transducers in hopes of organizing the highly varied
      research on cervical auscultation. It investigates where on the body these
      transducers are placed in order to record a signal as well as the collection of
      analog and digital filtering techniques used to further improve the signal
      quality. It also presents the wide array of methods and features used to
      characterize these signals, ranging from simply counting the number of swallows
      that occur over a period of time to calculating various descriptive features in
      the time, frequency, and phase space domains. Finally, this paper presents the
      algorithms that have been used to classify this data into 'normal' and 'abnormal'
      categories. Both linear as well as non-linear techniques are presented in this
      regard.

PMID- 26213660
TI  - Oxygen isotopes in tree rings record variation in precipitation delta18O and
      amount effects in the south of Mexico.
AB  - [1] Natural archives of oxygen isotopes in precipitation may be used to study
      changes in the hydrological cycle in the tropics, but their interpretation is not
      straightforward. We studied to which degree tree rings of Mimosa acantholoba from
      southern Mexico record variation in isotopic composition of precipitation and
      which climatic processes influence oxygen isotopes in tree rings (delta18Otr).
      Interannual variation in delta18Otr was highly synchronized between trees and
      closely related to isotopic composition of rain measured at San Salvador, 710 km
      to the southwest. Correlations with delta13C, growth, or local climate variables
      (temperature, cloud cover, vapor pressure deficit (VPD)) were relatively low,
      indicating weak plant physiological influences. Interannual variation in
      delta18Otr correlated negatively with local rainfall amount and intensity.
      Correlations with the amount of precipitation extended along a 1000 km long
      stretch of the Pacific Central American coast, probably as a result of organized
      storm systems uniformly affecting rainfall in the region and its isotope signal;
      episodic heavy precipitation events, of which some are related to cyclones,
      deposit strongly 18O-depleted rain in the region and seem to have affected the
      delta18Otr signal. Large-scale controls on the isotope signature include
      variation in sea surface temperatures of tropical north Atlantic and Pacific
      Ocean. In conclusion, we show that delta18Otr of M. acantholoba can be used as a
      proxy for source water delta18O and that interannual variation in delta18Oprec is
      caused by a regional amount effect. This contrasts with delta18O signatures at
      continental sites where cumulative rainout processes dominate and thus provide a
      proxy for precipitation integrated over a much larger scale. Our results confirm
      that processes influencing climate-isotope relations differ between sites
      located, e.g., in the western Amazon versus coastal Mexico, and that tree ring
      isotope records can help in disentangling the processes influencing precipitation
      delta18O.

PMID- 26213661
TI  - A model-based insight into the coupling of nitrogen and sulfur cycles in a
      coastal upwelling system.
AB  - The biogeochemical cycling in oxygen-minimum zones (OMZs) is dominated by the
      interactions of microbial nitrogen transformations and, as recently observed in
      the Chilean upwelling system, also through the energetically less favorable
      remineralization of sulfate reduction. The latter process is masked, however, by
      rapid sulfide oxidation, most likely through nitrate reduction. Thus, the cryptic
      sulfur cycle links with the nitrogen cycle in OMZ settings. Here, we model the
      physical-chemical water column structure and the observed process rates as driven
      by formation and sinking of organic detritus, to quantify the nitrogen and sulfur
      cycles in the Chilean OMZ. A new biogeochemical submodule was developed and
      coupled to the Regional Ocean Model System (ROMS). The model results generally
      agree with the observed distribution of reactive species and the measured process
      rates. Modeled heterotrophic nitrate reduction and sulfate reduction are
      responsible for 47% and 36%, respectively, of organic remineralization in a 150 m
      deep zone below mixed layer. Anammox contributes to 61% of the fixed nitrogen
      lost to N2 gas, while the rest of the loss is through canonical denitrification
      as a combination of organic matter oxidation by nitrite reduction and sulfide
      driven denitrification. Mineralization coupled to heterotrophic nitrate reduction
      supplies ~48% of the ammonium required by anammox. Due to active sulfate
      reduction, model results suggest that sulfide-driven denitrification contributes
      to 36% of the nitrogen loss as N2 gas. Our model results highlight the importance
      of considering the coupled nitrogen and sulfur cycle in examining open-ocean
      anoxic processes under present, past, and future conditions.

PMID- 26213662
TI  - Management and climate contributions to satellite-derived active fire trends in
      the contiguous United States.
AB  - : Fires in croplands, plantations, and rangelands contribute significantly to
      fire emissions in the United States, yet are often overshadowed by wildland fires
      in efforts to develop inventories or estimate responses to climate change. Here
      we quantified decadal trends, interannual variability, and seasonality of Terra
      Moderate Resolution Imaging Spectroradiometer (MODIS) observations of active
      fires (thermal anomalies) as a function of management type in the contiguous U.S.
      during 2001-2010. We used the Monitoring Trends in Burn Severity database to
      identify active fires within the perimeter of large wildland fires and land cover
      maps to identify active fires in croplands. A third class of fires defined as
      prescribed/other included all residual satellite active fire detections. Large
      wildland fires were the most variable of all three fire types and had no
      significant annual trend in the contiguous U.S. during 2001-2010. Active fires in
      croplands, in contrast, increased at a rate of 3.4% per year. Cropland and
      prescribed/other fire types combined were responsible for 77% of the total active
      fire detections within the U.S and were most abundant in the south and southeast.
      In the west, cropland active fires decreased at a rate of 5.9% per year, likely
      in response to intensive air quality policies. Potential evaporation was a
      dominant regulator of the interannual variability of large wildland fires, but
      had a weaker influence on the other two fire types. Our analysis suggests it may
      be possible to modify landscape fire emissions within the U.S. by influencing the
      way fires are used in managed ecosystems. KEY POINTS: Wildland, cropland, and
      prescribed fires had different trends and patternsSensitivity to climate varied
      with fire typeIntensity of air quality regulation influenced cropland burning
      trends.

PMID- 26213663
TI  - A multidimensional stability model for predicting shallow landslide size and
      shape across landscapes.
AB  - The size of a shallow landslide is a fundamental control on both its hazard and
      geomorphic importance. Existing models are either unable to predict landslide
      size or are computationally intensive such that they cannot practically be
      applied across landscapes. We derive a model appropriate for natural slopes that
      is capable of predicting shallow landslide size but simple enough to be applied
      over entire watersheds. It accounts for lateral resistance by representing the
      forces acting on each margin of potential landslides using earth pressure theory
      and by representing root reinforcement as an exponential function of soil depth.
      We test our model's ability to predict failure of an observed landslide where the
      relevant parameters are well constrained by field data. The model predicts
      failure for the observed scar geometry and finds that larger or smaller conformal
      shapes are more stable. Numerical experiments demonstrate that friction on the
      boundaries of a potential landslide increases considerably the magnitude of
      lateral reinforcement, relative to that due to root cohesion alone. We find that
      there is a critical depth in both cohesive and cohesionless soils, resulting in a
      minimum size for failure, which is consistent with observed size-frequency
      distributions. Furthermore, the differential resistance on the boundaries of a
      potential landslide is responsible for a critical landslide shape which is longer
      than it is wide, consistent with observed aspect ratios. Finally, our results
      show that minimum size increases as approximately the square of failure surface
      depth, consistent with observed landslide depth-area data.

PMID- 26213665
TI  - Laboratory simulations of acid-sulfate weathering under volcanic hydrothermal
      conditions: Implications for early Mars.
AB  - We have completed laboratory experiments and thermochemical equilibrium models to
      investigate secondary mineral formation under conditions akin to volcanic,
      hydrothermal acid-sulfate weathering systems. Our research used the basaltic
      mineralogy at Cerro Negro Volcano, Nicaragua, characterized by plagioclase,
      pyroxene, olivine, and volcanic glass. These individual minerals and whole-rock
      field samples were reacted in the laboratory with 1 molal sulfuric acid at
      varying temperatures (65, 150, and 200 degrees C), fluid:rock weight ratios (1:1,
      4:1, and 10:1), and durations (1-60 days). Thermochemical equilibrium models were
      developed using Geochemist's Workbench. To understand the reaction products and
      fluids, we employed scanning electron microscopy/energy dispersive spectroscopy,
      X-ray diffraction, and inductively coupled plasma-atomic emission spectroscopy.
      The results of our experiments and models yielded major alteration minerals that
      include anhydrite, natroalunite, minor iron oxide, and amorphous Al-Si gel. We
      found that variations in experimental parameters did not drastically change the
      suite of minerals produced; instead, abundance, size, and crystallographic shape
      changed. Our results also suggest that it is essential to separate phases formed
      during experiments from those formed during fluid evaporation to fully understand
      the reaction processes. Our laboratory reacted and model predicted products are
      consistent with the mineralogy observed at places on Mars. However, our results
      indicate that determination of the formation conditions requires microscopic
      imagery and regional context, as well as a thorough understanding of
      contributions from both experiment precipitation and fluid evaporation minerals.

PMID- 26213664
TI  - Radiostratigraphy and age structure of the Greenland Ice Sheet.
AB  - : Several decades of ice-penetrating radar surveys of the Greenland and Antarctic
      ice sheets have observed numerous widespread internal reflections. Analysis of
      this radiostratigraphy has produced valuable insights into ice sheet dynamics and
      motivates additional mapping of these reflections. Here we present a
      comprehensive deep radiostratigraphy of the Greenland Ice Sheet from airborne
      deep ice-penetrating radar data collected over Greenland by The University of
      Kansas between 1993 and 2013. To map this radiostratigraphy efficiently, we
      developed new techniques for predicting reflection slope from the phase recorded
      by coherent radars. When integrated along track, these slope fields predict the
      radiostratigraphy and simplify semiautomatic reflection tracing. Core
      intersecting reflections were dated using synchronized depth-age relationships
      for six deep ice cores. Additional reflections were dated by matching reflections
      between transects and by extending reflection-inferred depth-age relationships
      using the local effective vertical strain rate. The oldest reflections, dating to
      the Eemian period, are found mostly in the northern part of the ice sheet. Within
      the onset regions of several fast-flowing outlet glaciers and ice streams,
      reflections typically do not conform to the bed topography. Disrupted
      radiostratigraphy is also observed in a region north of the Northeast Greenland
      Ice Stream that is not presently flowing rapidly. Dated reflections are used to
      generate a gridded age volume for most of the ice sheet and also to determine the
      depths of key climate transitions that were not observed directly. This
      radiostratigraphy provides a new constraint on the dynamics and history of the
      Greenland Ice Sheet. KEY POINTS: Phase information predicts reflection slope and
      simplifies reflection tracingReflections can be dated away from ice cores using a
      simple ice flow modelRadiostratigraphy is often disrupted near the onset of fast
      ice flow.

PMID- 26213666
TI  - Surface energy budget and thermal inertia at Gale Crater: Calculations from
      ground-based measurements.
AB  - The analysis of the surface energy budget (SEB) yields insights into soil
      atmosphere interactions and local climates, while the analysis of the thermal
      inertia (I) of shallow subsurfaces provides context for evaluating geological
      features. Mars orbital data have been used to determine thermal inertias at
      horizontal scales of ~104 m2 to ~107 m2. Here we use measurements of ground
      temperature and atmospheric variables by Curiosity to calculate thermal inertias
      at Gale Crater at horizontal scales of ~102 m2. We analyze three sols
      representing distinct environmental conditions and soil properties, sol 82 at
      Rocknest (RCK), sol 112 at Point Lake (PL), and sol 139 at Yellowknife Bay (YKB).
      Our results indicate that the largest thermal inertia I = 452 J m-2 K-1 s-1/2 (SI
      units used throughout this article) is found at YKB followed by PL with I = 306
      and RCK with I = 295. These values are consistent with the expected thermal
      inertias for the types of terrain imaged by Mastcam and with previous satellite
      estimations at Gale Crater. We also calculate the SEB using data from
      measurements by Curiosity's Rover Environmental Monitoring Station and dust
      opacity values derived from measurements by Mastcam. The knowledge of the SEB and
      thermal inertia has the potential to enhance our understanding of the climate,
      the geology, and the habitability of Mars.

PMID- 26213667
TI  - Mars Science Laboratory relative humidity observations: Initial results.
AB  - : The Mars Science Laboratory (MSL) made a successful landing at Gale crater
      early August 2012. MSL has an environmental instrument package called the Rover
      Environmental Monitoring Station (REMS) as a part of its scientific payload. REMS
      comprises instrumentation for the observation of atmospheric pressure,
      temperature of the air, ground temperature, wind speed and direction, relative
      humidity (REMS-H), and UV measurements. We concentrate on describing the REMS-H
      measurement performance and initial observations during the first 100 MSL sols as
      well as constraining the REMS-H results by comparing them with earlier
      observations and modeling results. The REMS-H device is based on polymeric
      capacitive humidity sensors developed by Vaisala Inc., and it makes use of
      transducer electronics section placed in the vicinity of the three humidity
      sensor heads. The humidity device is mounted on the REMS boom providing
      ventilation with the ambient atmosphere through a filter protecting the device
      from airborne dust. The final relative humidity results appear to be convincing
      and are aligned with earlier indirect observations of the total atmospheric
      precipitable water content. The water mixing ratio in the atmospheric surface
      layer appears to vary between 30 and 75 ppm. When assuming uniform mixing, the
      precipitable water content of the atmosphere is ranging from a few to six
      precipitable micrometers. KEY POINTS: Atmospheric water mixing ratio at Gale
      crater varies from 30 to 140 ppmMSL relative humidity observation provides good
      dataHighest detected relative humidity reading during first MSL 100 sols is RH75.

PMID- 26213668
TI  - Diagenesis and clay mineral formation at Gale Crater, Mars.
AB  - The Mars Science Laboratory rover Curiosity found host rocks of basaltic
      composition and alteration assemblages containing clay minerals at Yellowknife
      Bay, Gale Crater. On the basis of the observed host rock and alteration minerals,
      we present results of equilibrium thermochemical modeling of the Sheepbed
      mudstones of Yellowknife Bay in order to constrain the formation conditions of
      its secondary mineral assemblage. Building on conclusions from sedimentary
      observations by the Mars Science Laboratory team, we assume diagenetic, in situ
      alteration. The modeling shows that the mineral assemblage formed by the reaction
      of a CO2-poor and oxidizing, dilute aqueous solution (Gale Portage Water) in an
      open system with the Fe-rich basaltic-composition sedimentary rocks at 10-50
      degrees C and water/rock ratio (mass of rock reacted with the starting fluid) of
      100-1000, pH of ?7.5-12. Model alteration assemblages predominantly contain
      phyllosilicates (Fe-smectite, chlorite), the bulk composition of a mixture of
      which is close to that of saponite inferred from Chemistry and Mineralogy data
      and to that of saponite observed in the nakhlite Martian meteorites and
      terrestrial analogues. To match the observed clay mineral chemistry,
      inhomogeneous dissolution dominated by the amorphous phase and olivine is
      required. We therefore deduce a dissolving composition of approximately 70%
      amorphous material, with 20% olivine, and 10% whole rock component.

PMID- 26213669
TI  - Instability of some equatorially trapped waves.
AB  - [1] A high-frequency asymptotics approach within the Lagrangian framework shows
      that some exact equatorially trapped three-dimensional waves are linearly
      unstable when their steepness exceeds a specific threshold. Citation: Constantin,
      A., and P. Germain (2013), Instability of some equatorially trapped waves, J.
      Geophys. Res. Oceans, 118, 2802-2810, doi:10.1002/jgrc.20219.

PMID- 26213670
TI  - A 3-D variational assimilation scheme in coupled transport-biogeochemical models:
      Forecast of Mediterranean biogeochemical properties.
AB  - [1] Increasing attention is dedicated to the implementation of suitable marine
      forecast systems for the estimate of the state of the ocean. Within the framework
      of the European MyOcean infrastructure, the pre-existing short-term Mediterranean
      Sea biogeochemistry operational forecast system has been upgraded by assimilating
      remotely sensed ocean color data in the coupled transport-biogeochemical model
      OPATM-BFM using a 3-D variational data assimilation (3D-VAR) procedure. In the
      present work, the 3D-VAR scheme is used to correct the four phytoplankton
      functional groups included in the OPATM-BFM in the period July 2007 to September
      2008. The 3D-VAR scheme decomposes the error covariance matrix using a sequence
      of different operators that account separately for vertical covariance,
      horizontal covariance, and covariance among biogeochemical variables. The
      assimilation solution is found in a reduced dimensional space, and the innovation
      for the biogeochemical variables is obtained by the sequential application of the
      covariance operators. Results show a general improvement in the forecast skill,
      providing a correction of the basin-scale bias of surface chlorophyll
      concentration and of the local-scale spatial and temporal dynamics of typical
      bloom events. Further, analysis of the assimilation skill provides insights into
      the functioning of the model. The computational costs of the assimilation scheme
      adopted are low compared to other assimilation techniques, and its modular
      structure facilitates further developments. The 3D-VAR scheme results especially
      suitable for implementation within a biogeochemistry operational forecast system.

PMID- 26213671
TI  - The great 2012 Arctic Ocean summer cyclone enhanced biological productivity on
      the shelves.
AB  - [1] A coupled biophysical model is used to examine the impact of the great Arctic
      cyclone of early August 2012 on the marine planktonic ecosystem in the Pacific
      sector of the Arctic Ocean (PSA). Model results indicate that the cyclone
      influences the marine planktonic ecosystem by enhancing productivity on the
      shelves of the Chukchi, East Siberian, and Laptev seas during the storm. Although
      the cyclone's passage in the PSA lasted only a few days, the simulated biological
      effects on the shelves last 1 month or longer. At some locations on the shelves,
      primary productivity (PP) increases by up to 90% and phytoplankton biomass by up
      to 40% in the wake of the cyclone. The increase in zooplankton biomass is up to
      18% on 31 August and remains 10% on 15 September, more than 1 month after the
      storm. In the central PSA, however, model simulations indicate a decrease in PP
      and plankton biomass. The biological gain on the shelves and loss in the central
      PSA are linked to two factors. (1) The cyclone enhances mixing in the upper
      ocean, which increases nutrient availability in the surface waters of the
      shelves; enhanced mixing in the central PSA does not increase productivity
      because nutrients there are mostly depleted through summer draw down by the time
      of the cyclone's passage. (2) The cyclone also induces divergence, resulting from
      the cyclone's low-pressure system that drives cyclonic sea ice and upper ocean
      circulation, which transports more plankton biomass onto the shelves from the
      central PSA. The simulated biological gain on the shelves is greater than the
      loss in the central PSA, and therefore, the production on average over the entire
      PSA is increased by the cyclone. Because the gain on the shelves is offset by the
      loss in the central PSA, the average increase over the entire PSA is moderate and
      lasts only about 10 days. The generally positive impact of cyclones on the marine
      ecosystem in the Arctic, particularly on the shelves, is likely to grow with
      increasing summer cyclone activity if the Arctic continues to warm and the ice
      cover continues to shrink.

PMID- 26213672
TI  - The salinity signature of the cross-shelf exchanges in the Southwestern Atlantic
      Ocean: Satellite observations.
AB  - : Satellite-derived sea surface salinity (SSS) data from Aquarius and SMOS are
      used to study the shelf-open ocean exchanges in the western South Atlantic near
      35 degrees S. Away from the tropics, these exchanges cause the largest SSS
      variability throughout the South Atlantic. The data reveal a well-defined
      seasonal pattern of SSS during the analyzed period and of the location of the
      export of low-salinity shelf waters. In spring and summer, low-salinity waters
      over the shelf expand offshore and are transferred to the open ocean primarily
      southeast of the river mouth (from 36 degrees S to 37 degrees 30'S). In contrast,
      in fall and winter, low-salinity waters extend along a coastal plume and the
      export path to the open ocean distributes along the offshore edge of the plume.
      The strong seasonal SSS pattern is modulated by the seasonality of the along
      shelf component of the wind stress over the shelf. However, the combined analysis
      of SSS, satellite-derived sea surface elevation and surface velocity data suggest
      that the precise location of the export of shelf waters depends on offshore
      circulation patterns, such as the location of the Brazil Malvinas Confluence and
      mesoscale eddies and meanders of the Brazil Current. The satellite data indicate
      that in summer, mixtures of low-salinity shelf waters are swiftly driven toward
      the ocean interior along the axis of the Brazil/Malvinas Confluence. In winter,
      episodic wind reversals force the low-salinity coastal plume offshore where they
      mix with tropical waters within the Brazil Current and create a warmer variety of
      low-salinity waters in the open ocean. KEY POINTS: Satellite salinity sensors
      capture low-salinity detrainment events from shelves SW Atlantic low-salinity
      detrainments cause highest basin-scale variability In summer low-salinity
      detrainments cause extended low-salinity anomalies.

PMID- 26213673
TI  - The salinity signature of the cross-shelf exchanges in the Southwestern Atlantic
      Ocean: Numerical simulations.
AB  - A high-resolution model is used to characterize the dominant patterns of sea
      surface salinity (SSS) variability generated by the freshwater discharges of the
      Rio de la Plata (RdlP) and the Patos/Mirim Lagoon in the southwestern Atlantic
      region. We identify three dominant modes of SSS variability. The first two, which
      have been discussed in previous studies, represent the seasonal and the
      interannual variations of the freshwater plumes over the continental shelf. The
      third mode of SSS variability, which has not been discussed hitherto, represents
      the salinity exchanges between the shelf and the deep ocean. A diagnostic study
      using floats and passive tracers identifies the pathways taken by the freshwater
      plumes. During the austral winter (JJA), the plumes leave the shelf region north
      of the BMC. During the austral summer (DJF), the plumes are entrained more
      directly into the BMC. A sensitivity study indicates that the high-frequency
      component of the wind stress forcing controls the vertical structure of the
      plumes while the low-frequency component of the wind stress forcing and the
      interannual variations of the RdlP discharge controls the horizontal structure of
      the plumes. Dynamical analysis reveals that the cross-shelf flow has a dominant
      barotropic structure and, therefore, the SSS anomalies detected by Aquarius
      represent net mass exchanges between the shelf and the deep ocean. The net cross
      shelf volume flux is 1.21 Sv. This outflow is largely compensated by an inflow
      from the Patagonian shelf.

PMID- 26213674
TI  - On the nature of the sea ice albedo feedback in simple models.
AB  - We examine the nature of the ice-albedo feedback in a long-standing approach used
      in the dynamic-thermodynamic modeling of sea ice. The central issue examined is
      how the evolution of the ice area is treated when modeling a partial ice cover
      using a two-category-thickness scheme; thin sea ice and open water in one
      category and "thick" sea ice in the second. The problem with the scheme is that
      the area evolution is handled in a manner that violates the basic rules of
      calculus, which leads to a neglected area evolution term that is equivalent to
      neglecting a leading-order latent heat flux. We demonstrate the consequences by
      constructing energy balance models with a fractional ice cover and studying them
      under the influence of increased radiative forcing. It is shown that the
      neglected flux is particularly important in a decaying ice cover approaching the
      transitions to seasonal or ice-free conditions. Clearly, a mishandling of the
      evolution of the ice area has leading-order effects on the ice-albedo feedback.
      Accordingly, it may be of considerable importance to reexamine the relevant
      climate model schemes and to begin the process of converting them to fully
      resolve the sea ice thickness distribution in a manner such as remapping, which
      does not in principle suffer from the pathology we describe.

PMID- 26213675
TI  - Decadal trends in global pelagic ocean chlorophyll: A new assessment integrating
      multiple satellites, in situ data, and models.
AB  - Quantifying change in ocean biology using satellites is a major scientific
      objective. We document trends globally for the period 1998-2012 by integrating
      three diverse methodologies: ocean color data from multiple satellites, bias
      correction methods based on in situ data, and data assimilation to provide a
      consistent and complete global representation free of sampling biases. The
      results indicated no significant trend in global pelagic ocean chlorophyll over
      the 15 year data record. These results were consistent with previous findings
      that were based on the first 6 years and first 10 years of the SeaWiFS mission.
      However, all of the Northern Hemisphere basins (north of 10 degrees  latitude),
      as well as the Equatorial Indian basin, exhibited significant declines in
      chlorophyll. Trend maps showed the local trends and their change in percent per
      year. These trend maps were compared with several other previous efforts using
      only a single sensor (SeaWiFS) and more limited time series, showing remarkable
      consistency. These results suggested the present effort provides a path forward
      to quantifying global ocean trends using multiple satellite missions, which is
      essential if we are to understand the state, variability, and possible changes in
      the global oceans over longer time scales.

PMID- 26213676
TI  - Salinity fronts in the tropical Pacific Ocean.
AB  - This study delineates the salinity fronts (SF) across the tropical Pacific, and
      describes their variability and regional dynamical significance using Aquarius
      satellite observations. From the monthly maps of the SF, we find that the SF in
      the tropical Pacific are (1) usually observed around the boundaries of the fresh
      pool under the intertropical convergence zone (ITCZ), (2) stronger in boreal
      autumn than in other seasons, and (3) usually stronger in the eastern Pacific
      than in the western Pacific. The relationship between the SF and the
      precipitation and the surface velocity are also discussed. We further present
      detailed analysis of the SF in three key tropical Pacific regions. Extending
      zonally around the ITCZ, where the temperature is nearly homogeneous, we find the
      strong SF of 1.2 psu from 7 degrees  to 11 degrees N to be the main contributor
      of the horizontal density difference of 0.8 kg/m3. In the eastern Pacific, we
      observe a southward extension of the SF in the boreal spring that could be driven
      by both precipitation and horizontal advection. In the western Pacific, the
      importance of these newly resolved SF associated with the western Pacific
      warm/fresh pool and El Nino southern oscillations are also discussed in the
      context of prior literature. The main conclusions of this study are that (a)
      Aquarius satellite salinity measurements reveal the heretofore unknown
      proliferation, structure, and variability of surface salinity fronts, and that
      (b) the fine-scale structures of the SF in the tropical Pacific yield important
      new information on the regional air-sea interaction and the upper ocean dynamics.

PMID- 26213677
TI  - Costs of Development and Maintenance of an Internet Program for Teens with Type 1
      Diabetes.
AB  - Many adolescents with type 1 diabetes (T1D) have difficulty completing self
      management tasks within the context of their social environments. Group-based
      approaches to psycho-educational support have been shown to prevent declines in
      glucose control, but are challenging to implement due to youths' many activities
      and costs. A novel solution is providing psycho-educational support via the
      internet. The purpose of this study is to describe the cost of developing and
      maintaining two internet psycho-educational programs, both of which have been
      shown to improve health outcomes in adolescents with T1D. We calculated actual
      costs of personnel and programming in the development of TEENCOPETM and Managing
      Diabetes, two highly interactive programs that were evaluated in a multi-site
      clinical trial (n=320). Cost calculations were set at U.S. dollars and converted
      to value for 2013 as expenses were incurred over 6 years. Development costs over
      1.5 years totaled $324,609, with the majority of costs being for personnel to
      develop and write content in a creative and engaging format, to get feedback from
      teens on content and a prototype, and IT programming. Maintenance of the program,
      including IT support, a part-time moderator to assure safety of the discussion
      board (0.5-1 hour/week), and yearly update of content was $43,845/year, or
      $137.00 per youth over 4.5 years. Overall, program and site development were
      relatively expensive, but the program reach was high, including non-white youth
      from 4 geographically distinct regions. Once developed, maintenance was minimal.
      With greater dissemination, cost-per-youth would decrease markedly, beginning to
      offset the high development expense.

PMID- 26213678
TI  - The creation of modulated monoclinic aperiodic composites in n-alkane/urea
      compounds.
AB  - n-Dodecane/urea is a member of the prototype series of n-alkane/urea inclusion
      compounds. At room temperature, it presents a quasi-one dimensional liquid-like
      state for the confined guest molecules within the rigid, hexagonal framework of
      the urea host. At lower temperatures, we report the existence of two other
      phases. Below Tc=248 K there appears a phase with rank four superspace group
      P6122(00gamma), the one typically observed at room temperature in n-alkane/urea
      compounds with longer guest molecules. A misfit parameter, defined by the ratio
      gamma=ch /cg (chost/cguest), is found to be 0.632+/-0.005. Below Tc1=123 K, a
      monoclinic modulated phase is created with a constant shift along c of the guest
      molecules in adjacent channels. The maximal monoclinic space group for this
      structure is P1211(alpha0gamma). Analogies and differences with n-heptane/urea,
      which also presents a monoclinic, modulated low-temperature phase, are discussed.

PMID- 26213679
TI  - Relationship of biofilm formation and different virulence genes in uropathogenic
      Escherichia coli isolates from Northwest Iran.
AB  - BACKGROUND AND OBJECTIVES: The Escherichia coli (E. coli) bacterium is one of the
      main causative agents of urinary tract infections (UTI) worldwide. The ability of
      this bacterium to form biofilms on medical devices such as catheters plays an
      important role in the development of UTI. The aim of the present study was to
      investigate the possible relationship between virulence factors and biofilm
      formation of E. coli isolates responsible for urinary tract infection. MATERIALS
      AND METHODS: A total of 100 E. coli isolates isolated from patients with UTI were
      collected and characterized by routine bacteriological methods. In vitro biofilm
      formation by these isolates was determined using the 96-well microtiter-plate
      test, and the presence of fimA, papC, and hly virulence genes was examined by PCR
      assay. Data analysis was performed using SPSS 16.0 software. RESULTS: From 100 E.
      coli isolates isolated from UTIs, 92% were shown to be biofilm positive. The
      genes papC, fimA, and hly were detected in 43%, 94% and 26% of isolates,
      respectively. Biofilm formation in isolates that expressed papC, fimA, and hly
      genes was 100%, 93%, and 100%, respectively. A significant relationship was found
      between presence of the papC gene and biofilm formation in E. coli isolates
      isolated from UTI (P<0.01), but there was no statistically significant
      correlation between presence of fimA and hly genes with biofilm formation
      (P<0.072, P<0.104). CONCLUSION: RESULTS showed that fimA and hly genes do not
      seem to be necessary or sufficient for the production of biofilm in E. coli, but
      the presence of papC correlates with increased biofilm formation of urinary tract
      isolates. Overall, the presence of fimA, papC, and hly virulence genes coincides
      with in vitro biofilm formation in uropathogenic E. coli isolates.

PMID- 26213680
TI  - Epidemiological alteration in pathogens found in ground meat in Iran: unexpected
      predominance of vancomycin-resistant Enterococcus faecalis.
AB  - Colonization of the human and animal intestinal tract with potential pathogenic
      bacteria is correlated with the risk of contamination of food products. The
      current study analyzed the prevalence of Enterococcus faecalis and Escherichia
      coli O157H7 in ground meat in Ilam, Iran. Both index organisms were identified
      following standard food microbiological methods. For E. faecalis, the
      susceptibility to vancomycin was tested, and PCR was used to check for the vanA
      gene. E. faecalis was present in all 24 ground meat samples, with no E. coli
      O157H7 detected in samples. The analysis showed the presence of the vanA gene in
      5/24 vancomycin resistant enterococci. In conclusion, this study for the first
      time demonstrates the presence of vancomycin-resistant enterococci in ground meat
      in Iran. This observation warrants further epidemiologic investigation and should
      be followed up in the future. 

PMID- 26213681
TI  - Mechanistic Role of MicroRNA in Cancer Chemoprevention by Nonsteroidal Anti
      inflammatory Drugs.
AB  - Over the past several decades, studies have documented the significance of
      nonsteroidal anti-inflammatory drugs (NSAIDs) on cancer chemoprevention by
      lowering incidence and slowing down progression of malignant disease, which
      consequently lead to decline of cancer-related mortality and improvement of
      disease progression free survival (PFS). Inhibition of cyclooxygenase (COX) has
      been primarily believed to be the key mechanism responsible for anticancer
      activity of NSAIDs, while the serious toxicity caused by COX inhibitory effect
      reduces the enthusiasm to use NSAIDs as chemoprevention agents in the clinic.
      Recently, more and more studies demonstrate that non-COX inhibitory mechanisms
      may account for anticancer properties of NSAIDs, at least partially, which
      potentially support the indication of NSAIDs on cancer chemoprevention. MicroRNAs
      (miRNAs) are a set of non-coding and small RNA molecules with master regulatory
      effect on over 30% human genes through the post-transcriptional and translational
      modulation. Although miRNAs have been reported to be involved in many normal and
      pathological processes including cell proliferation, apoptosis, differentiation,
      as well as tumorigenesis, their roles in NSAIDs' properties of cancer
      chemoprevention have not yet been studied exclusively. Here, we will review the
      prior studies reporting interactions between miRNAs and COX/non-COX pathways with
      intent to provide insights into better understanding molecular mechanisms of
      cancer chemoprevention by NSAIDs.

PMID- 26213682
TI  - The acute effect of exercise modality and nutrition manipulations on post
      exercise resting energy expenditure and respiratory exchange ratio in women: a
      randomized trial.
AB  - BACKGROUND: The purpose of this study was to examine the effect of exercise
      modality and pre-exercise carbohydrate (CHO) or protein (PRO) ingestion on post
      exercise resting energy expenditure (REE) and respiratory exchange ratio (RER) in
      women. METHODS: Twenty recreationally active women (mean +/- SD; age 24.6 +/- 3.9
      years; height 164.4 +/- 6.6 cm; weight 62.7 +/- 6.6 kg) participated in this
      randomized, crossover, double-blind study. Each participant completed six
      exercise sessions, consisting of three exercise modalities: aerobic endurance
      exercise (AEE), high-intensity interval running (HIIT), and high-intensity
      resistance training (HIRT); and two acute nutritional interventions: CHO and PRO.
      Salivary samples were collected before each exercise session to determine
      estradiol-beta-17 and before and after to quantify cortisol. Post-exercise REE
      and RER were analyzed via indirect calorimetry at the following: baseline,
      immediately post (IP), 30 minutes (30 min) post, and 60 minutes (60 min) post
      exercise. A mixed effects linear regression model, controlling for estradiol, was
      used to compare mean longitudinal changes in REE and RER. RESULTS: On average,
      HIIT produced a greater REE than AEE and HIRT (p < 0.001) post exercise. Effects
      of AEE and HIRT were not significantly different for post-exercise REE (p =
      0.1331). On average, HIIT produced lower RER compared to either AEE or HIRT after
      30 min (p < 0.001 and p = 0.0169, respectively) and compared to AEE after 60 min
      (p = 0.0020). On average, pre-exercise PRO ingestion increased post-exercise REE
      (p = 0.0076) and decreased post-exercise RER (p < 0.0001) compared to pre
      exercise CHO ingestion. CONCLUSION: HIIT resulted in the largest increase in REE
      and largest reduction in RER.

PMID- 26213683
TI  - Communication practices about HPV testing among providers in Federally Qualified
      Health Centers.
AB  - OBJECTIVE: Little is known about the information providers share with patients
      when ordering a co-test, or combined human papillomavirus (HPV) and Papanicolaou
      (Pap) test, for cervical cancer screening. We assessed provider perceptions of
      such communication practices with female patients aged 30-60 years. METHODS: We
      analyzed data from 98 providers in 15 Federally Qualified Health Center clinics
      across Illinois (2009-2010). RESULTS: About 70% of the providers reported that
      when ordering a co-test, they would usually or always communicate information
      about the HPV test to their patients, explain the test detects a sexually
      transmitted infection, and discuss how the test results may determine their next
      screening interval. Most (>85%) reported that they were comfortable discussing co
      test results. Compared with concordant positive results (HPV positive/Pap
      positive), providers were more likely to perceive that discordant results (HPV
      positive/Pap negative) would be too complex for patients to understand (25% vs.
      15%, p = 0.006), and make patients feel less assured that they were getting the
      best standard of care (67% vs. 88%, p < 0.001). CONCLUSION: As HPV testing plays
      a more prominent role in cervical cancer screening, more attention should be
      given to communications between providers and patients about the benefits and
      harms of different screening options.

PMID- 26213684
TI  - Polygenic Case of Long QT Syndrome Confirmed through Functional Characterization
      Informs the Interpretation of Genetic Screening Results.

PMID- 26213685
TI  - The use of urinary and kidney SILAM proteomics to monitor kidney response to high
      dose morpholino oligonucleotides in the mdx mouse.
AB  - Phosphorodiamidate morpholino oligonucleotides (PMO) are used as a promising exon
      skipping gene therapy for Duchenne Muscular Dystrophy (DMD). One potential
      complication of high dose PMO therapy is its transient accumulation in the
      kidneys. Therefore new urinary biomarkers are needed to monitor this treatment.
      Here, we carried out a pilot proteomic profiling study using stable isotope
      labeling in mammals (SILAM) strategy to identify new biomarkers to monitor the
      effect of PMO on the kidneys of the dystrophin deficient mouse model for DMD (mdx
      23). We first assessed the baseline renal status of the mdx-23 mouse compared to
      the wild type (C57BL10) mouse, and then followed the renal outcome of mdx-23
      mouse treated with a single high dose intravenous PMO injection (800 mg/kg).
      Surprisingly, untreated mdx-23 mice showed evidence of renal injury at baseline,
      which was manifested by albuminuria, increased urine output, and changes in
      established urinary biomarker of acute kidney injury (AKI). The PMO treatment
      induced further transient renal injury, which peaked at 7 days, and returned to
      almost the baseline status at 30 days post-treatment. In the kidney, the SILAM
      approach followed by western blot validation identified changes in Meprin A
      subunit alpha at day 2, then returned to normal levels at day 7 and 30 after PMO
      injection. In the urine, SILAM approach identified an increase in Clusterin and
      gamma-glutamyl transpeptidase 1 as potential candidates to monitor the transient
      renal accumulation of PMO. These results, which were confirmed by Western blots
      or ELISA, demonstrate the value of the SILAM approach to identify new candidate
      biomarkers of renal injury in mdx-23 mice treated with high dose PMO. Chemical
      compounds studied in this article: Phosphorodiamidate morpholino (PubChem CID:
      22140692); isoflurane (PubChem CID: 3763); formic acid (PubChem CID: 284);
      acetonitrile (PubChem CID: 6342); acetone (PubChem CID: 180); methanol (PubChem
      CID: 887).

PMID- 26213686
TI  - Cancer biomarker discovery and validation.
AB  - With the emergence of genomic profiling technologies and selective molecular
      targeted therapies, biomarkers play an increasingly important role in the
      clinical management of cancer patients. Single gene/protein or multi-gene
      "signature"-based assays have been introduced to measure specific molecular
      pathway deregulations that guide therapeutic decision-making as predictive
      biomarkers. Genome-based prognostic biomarkers are also available for several
      cancer types for potential incorporation into clinical prognostic staging systems
      or practice guidelines. However, there is still a large gap between initial
      biomarker discovery studies and their clinical translation due to the challenges
      in the process of cancer biomarker development. In this review we summarize the
      steps of biomarker development, highlight key issues in successful validation and
      implementation, and overview representative examples in the oncology field. We
      also discuss regulatory issues and future perspectives in the era of big data
      analysis and precision medicine.

PMID- 26213687
TI  - Molecular and Genetic Characterization of Depression: Overlap with other
      Psychiatric Disorders and Aging.
AB  - Genome-wide expression and genotyping technologies have uncovered the genetic
      bases of complex diseases at unprecedented rates; However despite its heavy
      burden and high prevalence, the molecular characterization of major depressive
      disorder (MDD) has lagged behind. Transcriptome studies report multiple brain
      disturbances but are limited by small sample sizes. Genome-wide association
      studies (GWAS) report weak results but suggest overlapping genetic risk with
      other neuropsychiatric disorders. We performed systematic molecular
      characterization of altered brain function in MDD, using meta-analysis of
      differential expression in eight gene array studies in three corticolimbic brain
      regions in 101 subjects. The identified "metaA-MDD" genes suggest altered
      neurotrophic support, brain plasticity and neuronal signaling in MDD. Notably,
      metaA-MDD genes display low connectivity and hubness in coexpression networks,
      and uniform genomic distribution, consistent with diffuse polygenic mechanisms.
      We next integrated these findings with results from over 1800 published GWAS and
      show that genetic variations nearby metaA-MDD genes predict greater risk for
      neuropsychiatric disorders and notably for age-related phenotypes, but not for
      other medical illnesses, including those frequently co-morbid with depression, or
      body characteristics. Collectively, the intersection of unbiased investigations
      of gene function (transcriptome) and structure (GWAS) provides novel leads to
      investigate molecular mechanisms of MDD and suggest common biological pathways
      between depression, other neuropsychiatric diseases, and brain aging.

PMID- 26213688
TI  - Optimism and Cardiovascular Health: Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - OBJECTIVES: We examined the cross-sectional association between optimism and
      cardiovascular health (CVH). METHODS: We used data collected from adults aged 52
      84 who participated in the Multi-Ethnic Study of Atherosclerosis (MESA) (n=5,134)
      during the first follow-up visit (2002-2004). Multinomial logistic regression was
      used to examine associations of optimism with ideal and intermediate CVH (with
      reference being poor CVH), after adjusting for socio-demographic factors and
      psychological ill-being. RESULTS: Participants in the highest quartile of
      optimism were more likely to have intermediate [OR=1.51:95%CI=1.25,1.82] and
      ideal [OR=1.92:95%CI=1.30,2.85] CVH when compared to the least optimistic group.
      Individual CVH metrics of diet, physical activity, BMI, smoking, blood sugar and
      total cholesterol contributed to the overall association. CONCLUSIONS: We offer
      evidence for a cross-sectional association between optimism and CVH.

PMID- 26213689
TI  - Two Distinct Hepatitis C Virus Genotype 1a Clades Have Different Geographical
      Distribution and Association With Natural Resistance to NS3 Protease Inhibitors.
AB  - Background.  Hepatitis C virus (HCV) genotype 1 is the most prevalent worldwide.
      Subtype 1a, compared with 1b, shows lower response rates and higher propensity to
      select for drug resistance to NS3 and selected NS5A and nonnucleoside NS5B
      inhibitors. Two distinct clades of subtype 1a have been described. Methods. 
      Using Bayesian methodology, we performed a time-scaled phylogeny reconstruction
      of clade separation and characterized the geographic distribution, phylodynamics,
      and association with natural resistance variants of NS3 sequences from 362
      patients carrying subtype 1a HCV. Results.  All sequences segregated in 2 clearly
      distinct clades. Clade I showed an earlier origin from the common ancestor
      compared with clade II. Clade I virus was more prevalent in non-European
      countries, represented mostly by United States, compared with European (75.7% vs
      49.3%; P < .001). The prevalence of the natural NS3 variant Q80K, associated with
      resistance to the macrocyclic protease inhibitor simeprevir, was detected in
      51.6% of clade I and 0% of clade II (P < .001); clade I showed a lower genetic
      barrier for Q80K, whereas no sign of selective pressure at any protease inhibitor
      resistance-associated codon was detected. Conclusions.  Hepatitis C virus subtype
      1a clades have a clearly different distribution in Europe and the United States,
      and the natural resistance mutation Q80K is exclusively associated with clade I. 

PMID- 26213690
TI  - Cryptococcal Antigenemia in Immunocompromised Human Immunodeficiency Virus
      Patients in Rural Tanzania: A Preventable Cause of Early Mortality.
AB  - Background.  Cryptococcal meningitis is a leading cause of death in people living
      with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The
      World Health Organizations recommends pre-antiretroviral treatment (ART)
      cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/uL. We
      assessed the prevalence and outcome of cryptococcal antigenemia in rural southern
      Tanzania. Methods.  We conducted a retrospective study including all ART-naive
      adults with CD4 <150 cells/uL prospectively enrolled in the Kilombero and Ulanga
      Antiretroviral Cohort between 2008 and 2012. Cryptococcal antigen was assessed in
      cryopreserved pre-ART plasma. Cox regression estimated the composite outcome of
      death or loss to follow-up (LFU) by CRAG status and fluconazole use. Results.  Of
      750 ART-naive adults, 28 (3.7%) were CRAG-positive, corresponding to a prevalence
      of 4.4% (23 of 520) in CD4 <100 and 2.2% (5 of 230) in CD4 100-150 cells/uL.
      Within 1 year, 75% (21 of 28) of CRAG-positive and 42% (302 of 722) of CRAG
      negative patients were dead or LFU (P<.001), with no differences across CD4
      strata. Cryptococcal antigen positivity was an independent predictor of death or
      LFU after adjusting for relevant confounders (hazard ratio [HR], 2.50; 95%
      confidence interval [CI], 1.29-4.83; P = .006). Cryptococcal meningitis occurred
      in 39% (11 of 28) of CRAG-positive patients, with similar retention-in-care
      regardless of meningitis diagnosis (P = .8). Cryptococcal antigen titer >1:160
      was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24-8.41;
      P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients
      (HR, 0.18; 95% CI, .04-.78; P = .022). Conclusions.  Cryptococcal antigenemia
      predicted mortality or LFU among ART-naive HIV-infected persons with CD4 <150
      cells/uL, and fluconazole increased survival or retention-in-care, suggesting
      that targeted pre-ART CRAG screening may decrease early mortality or LFU. A CRAG
      screening threshold of CD4 <100 cells/uL missed 18% of CRAG-positive patients,
      suggesting guidelines should consider a higher threshold. 

PMID- 26213691
TI  - Nontuberculous Mycobacteria: An Underestimated Cause of Bioprosthetic Valve
      Infective Endocarditis.
AB  - Background.  Atypical mycobacteria, or nontuberculous mycobacteria (NTM), have
      been barely reported as infective endocarditis (IE) agents. Methods.  From
      January 2010 to December 2013, cardiac valve samples sent to our laboratory as
      cases of blood culture-negative suspected IE were analyzed by 16S rDNA polymerase
      chain reaction (PCR). When positive for NTM, hsp PCR allowed species
      identification. Demographic, clinical, echocardiographic, histopathological, and
      Ziehl-Neelsen staining data were then collected. Results.  Over the study period,
      6 of 370 cardiac valves (belonging to 5 patients in 3 hospitals) were positive
      for Mycobacterium chelonae (n = 5) and Mycobacterium lentiflavum (n = 1)
      exclusively on bioprosthetic material. The 5 patients presented to the hospital
      for heart failure without fever 7.1-18.9 months (median 13.1 months) after
      biological prosthetic valve implantation. Echocardiography revealed paravalvular
      regurgitation due to prosthesis dehiscence in all patients. Histopathological
      examination of the explanted material revealed inflammatory infiltrates in all
      specimens, 3 of which were associated with giant cells. Gram staining and
      conventional cultures remained negative, whereas Ziehl-Neelsen staining showed
      acid-fast bacilli in all patients. Allergic etiology was ruled out by antiporcine
      immunoglobulin E dosages. These 5 cases occurred exclusively on porcine
      bioprosthetic material, revealing a statistically significant association between
      bioprosthetic valves and NTM IE (P < .001). Conclusions.  The body of evidence
      confirmed the diagnosis of prosthetic IE. The statistically significant
      association between bioprosthetic valves and NTM IE encourages systematic Ziehl
      Neelsen staining of explanted bioprosthetic valves in case of early bioprosthesis
      dysfunction, even without an obvious sign of IE. In addition, we strongly
      question the cardiac bioprosthesis conditioning process after animal sacrifice. 

PMID- 26213692
TI  - Potential Influence of Staphylococcus aureus Clonal Complex 30 Genotype and
      Transcriptome on Hematogenous Infections.
AB  - Background.  The contemporary Staphylococcus aureus clonal complex (CC) 30
      lineage is associated with complicated infections, including endocarditis and
      osteomyelitis. This lineage diverged from the phage-type 80/81 S aureus clone
      responsible for a major bacterial epidemic of the 20th century. The genome and
      transcriptome features that contribute to complicated infections of the CC30
      lineage are unknown. Methods.  Twenty-nine clinical methicillin-resistant S
      aureus (MRSA) strains (8 from CC30 and 21 from other major CCs were evaluated for
      virulence using murine and Galleria mellonella sepsis models. Genomic features of
      CC30 were identified by comparative genome sequencing and RNA-Seq transcriptome
      analysis of the 29 strains and 31 previously sequenced S aureus genomes. Results.
      The CC30 isolates displayed lower virulence in the sepsis models compared with
      other CCs [P < .0001]. Comparisons of orthologous proteins and transcriptome
      analysis identified genes (eg, nitric oxide reductase) and changes in metabolic
      pathways (eg, pyrimidine metabolism) that contribute to the distinct CC30
      phenotype. Previously reported nonsynonymous single-nucleotide polymorphisms
      (SNPs) were found in accessory gene regulator C (agrC) and alpha-hemolysin (hla),
      molecules important for virulence. Additional nonsynonymous SNPs conserved across
      clinical CC30 isolates when compared with the first sequenced contemporary CC30
      clone, MRSA-16, were identified in multiple genes, suggesting continuing
      evolutionary divergence in this lineage. Conclusions.  Genomic and
      transcriptional analyses suggest that the CC30 lineage has acquired metabolic
      features that contribute to persistent and complicated infections. Absence of
      sepsis-induced mortality in animal models may be due in part to its unique
      genomic profile and suggests that specific genotypes of S aureus elicit distinct
      types of infection types. 

PMID- 26213693
TI  - Syphilis? An Unusual Cause of Surgical Emergency in a Human Immunodeficiency
      Virus-Infected Man.
AB  - We report on a human immunodeficiency virus-infected man undergoing urgent
      anorectal surgery, with multi-centimeter fungating masses discovered inside the
      anus. Initial pathology was inconclusive. After the patient developed a
      disseminated rash postoperatively determined to be secondary syphilis, the
      anorectal pathology was reviewed and Treponema pallidum DNA was amplified by
      polymerase chain reaction from the mass. 

PMID- 26213695
TI  - QuantitativeT2: interactive quantitative T2 MRI witnessed in mouse glioblastoma.
AB  - The aim of this study was to establish an advanced analytical platform for
      complex in vivo pathologies. We have developed a software program,
      QuantitativeT2, for voxel-based real-time quantitative T2 magnetic resonance
      imaging. We analyzed murine brain tumors to confirm feasibility of our method for
      neurological conditions. Anesthetized mice (with invasive gliomas, and controls)
      were imaged on a 9.4 Tesla scanner using a Carr-Purcell-Meiboom-Gill sequence.
      The multiecho T2 decays from axial brain slices were analyzed using
      QuantitativeT2. T2 distribution histograms demonstrated substantial
      characteristic differences between normal and pathological brain tissues. Voxel
      based quantitative maps of tissue water fraction (WF) and geometric mean T2
      (gmT2) revealed the heterogeneous alterations to water compartmentalization
      caused by pathology. The numeric distribution of WF and gmT2 indicated the extent
      of tumor infiltration. Relative evaluations between in vivo scans and ex vivo
      histology indicated that the T2s between 30 and 150 ms were related to cellular
      density and the integrity of the extracellular matrix. Overall, QuantitativeT2
      has demonstrated significant advancements in qT2 analysis with real-time
      operation. It is interactive with an intuitive workflow; can analyze data from
      many MR manufacturers; and is released as open-source code to encourage
      examination, improvement, and expansion of this method. 

PMID- 26213694
TI  - A Randomized Comparison of Anthropomorphic Changes With Preferred and Alternative
      Efavirenz-Based Antiretroviral Regimens in Diverse Multinational Settings.
AB  - Background.  Existing data on anthropomorphic changes in resource-limited
      settings primarily come from observational or cross-sectional studies. Data from
      randomized clinical trials are needed to inform treatment decisions in these
      areas of the world. Methods.  The AIDS Clinical Trials Group Prospective
      Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a
      prospective, randomized evaluation of the efficacy of emtricitabine/tenofovir +
      efavirenz (FTC/TDF + EFV) vs lamivudine/zidovudine + efavirenz (3TC/ZDV + EFV)
      for the initial treatment of human immunodeficiency virus (HIV)-1-infected
      individuals from resource-diverse settings. Changes in anthropomorphic measures
      were analyzed using mixed-effect models for repeated measurements, using all
      available measurements at weeks 48, 96, and 144. Intent-to-treat results are
      presented; as-treated results were similar. Results.  Five hundred twenty-six
      participants were randomized to FTC/TDF + EFV, and 519 participants were
      randomized to 3TC/ZDV + EFV. Significantly greater increases from baseline to
      week 144 were seen among those randomized to FTC/TDF + EFV vs 3TC/ZDV + EFV in
      all measures except waist-to-hip ratio, with the following mean changes: weight,
      4.8 vs 3.0 kg; body mass index, 1.8 vs 1.1 kg/m(2); mid-arm, 1.7 vs 0.7 cm;
      waist, 5.2 vs 4.3 cm; hip, 3.8 vs 1.4 cm; and mid-thigh circumference, 3.1 vs 0.9
      cm. There were 7 clinical diagnoses of lipoatrophy in the 3TC/ZDV + EFV arm
      compared with none in the FTC/TDF + EFV arm. The proportion of overweight or
      obese participants increased from 25% (week 0) to 42% (week 144) for FTC/TDF +
      EFV and from 26% to 38% for 3TC/ZDV + EFV. Conclusions.  Our findings support
      first-line use of FTC/TDF + EFV in resource-limited settings and emphasize the
      need for interventions to limit weight gain among overweight or obese HIV
      infected participants in all settings. 

PMID- 26213696
TI  - Modulation of Epidermal Growth Factor Stimulated ERK Phosphorylation and Cell
      Motility by Inositol Trisphosphate Kinase.
AB  - Epidermal growth factor [EGF] mediated stimulation of its receptor in endothelial
      cell [EC] is accompanied by phosphorylation of the EGF-receptor [EGFR] and
      activation of phospholipase C-gamma, resulting in the breakdown of
      phosphatidylinositol(4,5)-bisphosphate and generating inositol (1,4,5)
      trisphosphate [IP3] and diacylglycerol. IP3 thus formed can be further converted
      to inositol (1,3,4,5)-tetrakisphosphate [IP4] by an enzyme called IP3-kinase
      [IP3K]. In this study we have investigated the effect of modulation of
      intracellular IP3K activity by the use of an inhibitor, 2-trifluoromethyl [6-(4
      nitrobenzyl)-purine] [IP3KI] and siRNA against IP3KB on EGF-induced ERK
      phosphorylation and cell motility. EGF stimulated ERK-phosphorylation that has
      been implicated in EGF-stimulated cell migration was inhibited by both IP3KI and
      siRNA against IP3KB. Inhibition of ERK-phosphorylation was accompanied by
      decreased cell migration in the presence of IP3KI.

PMID- 26213697
TI  - Avascular Necrosis of the Femoral Head: Are Any Genes Involved?
AB  - Avascular necrosis of the femoral head (ANFH) is a pathologic process that
      results from interruption of blood supply to the femur bone resulting in the
      death of bone cells and collapse of the femoral head. Nontraumatic ANFH continues
      to be a significant challenge to orthopedic surgeons. While the exact mechanisms
      remain elusive, many new insights have emerged from research in the last decade
      that has given us a clearer picture of the pathogenesis of nontraumatic ANFH.
      Progression to the end stage of ANFH appears to be related to five main
      mechanisms: hypercoagulable conditions, angiogenesis suppressions,
      hyperadipogenesis, heritable states, and switching the bone remodelling into bone
      resorption. Researchers have been examining the pathogenic mechanisms of ANFH but
      none of these theories have been firmly confirmed although some appear more
      plausible than the others. All of these factors can switch bone remodelling into
      bone resorption, which can further lead to ANFH progression ending up to femoral
      head collapse. 

PMID- 26213698
TI  - Radial Tunnel Syndrome, Diagnostic and Treatment Dilemma.
AB  - Radial tunnel syndrome is a disease which we should consider it in elbow and
      forearm pains. It is diagnosed with lateral elbow and dorsal forearm pain may
      radiate to the wrist and dorsum of the fingers. The disease is more prevalent in
      women with the age of 30 to 50 years old. It occurs by intermittent compression
      on the radial nerve from the radial head to the inferior border of the supinator
      muscle, without obvious extensor muscle weakness. Compression could happen in
      five different sites but the arcade of Frose is the most common area that radial
      nerve is compressed. To diagnosis radial tunnel syndrome, clinical examination is
      more important than paraclinic tests such as electrodiagnsic test and imaging
      studies. The exact site of the pain which can more specified by rule of nine test
      and weakness of the third finger and wrist extension are valuable physical exams
      to diagnosis. MRI studies my show muscle edema or atrophy along the distribution
      of the posterior interosseous nerve. Although non-surgical treatments such as
      rest, NSAIDs, injections and physiotherapy do not believe to have permanent
      relief, but it is justify undergoing them before surgery. Surgery could diminish
      pain and symptoms in 67 to 93 percents of patients completely. 

PMID- 26213699
TI  - Reliability, Readability and Quality of Online Information about Femoracetabular
      Impingement.
AB  - BACKGROUND: The Internet has become the most widely-used source for patients
      seeking information more about their health and many sites geared towards this
      audience have gained widespread use in recent years. Additionally, many
      healthcare institutions publish their own patient-education web sites with
      information regarding common conditions. Little is known about how these
      resources impact patient health, though, as they have the potential both to
      inform and to misinform patients regarding their prognosis and possible
      treatments. In this study we investigated the reliability, readability and
      quality of information about femoracetabular impingement, a condition which
      commonly affects young patients. METHODS: The terms "hip impingement" and
      "femoracetabular impingement" were searched in Google(r) in November 2013 and the
      first 30 results were analyzed. The LIDA scale was used to assess website
      accessibility, usability and reliability. The DISCERN scale was used to assess
      reliability and quality of information. The FRE score was used to assess
      readability. RESULTS: The patient-oriented sites performed significantly worse in
      LIDA reliability, and DISCERN reliability. However, the FRE score was
      significantly higher in patient-oriented sites. CONCLUSION: According to our
      results, the websites intended to attract patients searching for information
      regarding femoroacetabular impingement are providing a highly accessible,
      readable information source, but do not appear to apply a comparable amount of
      rigor to scientific literature or healthcare practitioner websites in regard to
      matters such as citing sources for information, supplying methodology and
      including a publication date. This indicates that while these resources are
      easily accessed by patients, there is potential for them to be a source of
      misinformation.

PMID- 26213700
TI  - Ultrasound-guided Percutaneous Medial Pinning of Pediatric Supracondylar Humeral
      Fractures to avoid Ulnar Nerve Injury.
AB  - BACKGROUND: Medial pinning is one of the most controversial aspects of the
      surgical treatment of supracondylar fractures (SHF) owing to the risk of ulnar
      nerve injury. AIM: To evaluate the safety and usefulness of medial pinning for
      SHF using ultrasound imaging for ulnar nerve visualization. METHODS: Fifteen
      children, with a mean age of 60 months, with displaced SHF were treated with a
      crossed-pinning configuration after fracture reduction. Intraoperative ultrasound
      was used to guide medial pin insertion to avoid ulnar nerve injury. RESULTS:
      Cubital tunnel anatomy was easily identified in all children. All children showed
      a subluxating ulnar nerve that required elbow extension to about 90o before
      medial pin insertion. None suffered ulnar nerve dysfunction after using the
      referred technique. CONCLUSIONS: Although technically demanding, ultrasound may
      be a valuable adjuvant to avoid ulnar nerve injury while performing a medial
      pinning in pediatric SHF.

PMID- 26213701
TI  - Clinical Results of Meniscal Repair Using Submeniscal Horizontal Sutures.
AB  - BACKGROUND: Parts of the implants placed over the meniscus during meniscal repair
      can wear down the cartilage in the contact zones and cause chronic synovitis.
      Placing horizontal sutures under the meniscus may overcome this potential hazard.
      The purpose of this prospective study was to evaluate the midterm results of
      arthroscopic meniscal repair using submeniscally placed out-in horizontal
      sutures. METHODS: One hundred and three meniscal repairs with submeniscal
      horizontal out-in technique in 103 patients were performed between 2009 and 2012.
      Our indications for meniscal repair were all longitudinal tear in red-red and red
      white zone with acceptable tissue quality. Clinical evaluation included the
      Tegner and Lysholm knee scores and clinical success was defined as absence of
      joint-line tenderness, locking, swelling, and a negative McMurray test. RESULTS:
      The average follow-up was 19 months (range, 14 to 40 months). The time interval
      from injury to meniscal repair ranged from 2 days to 390 days (median, 96 days).
      At the end of follow-up, the clinical success rate was 86.5%. Fourteen of 103
      repaired menisci (13.5%) were considered failures according to Barrett's
      criteria. The mean Lysholm score significantly improved from 39.6 preoperatively
      to 84.5 postoperatively (P<0.001). Eighty five patients (82.5%) had an excellent
      or good result according to Lysholm knee score. Tegner activity score improved
      significantly (P<0.01) from an average of 3.4 (range, 2-6) preoperatively to 5.9
      (range, 5-8) postoperatively. Statistical analysis showed that age, simultaneous
      anterior cruciate ligament reconstruction, chronicity of injury did not affect
      the clinical outcome. CONCLUSION: Our results showed that acceptable midterm
      results are expected from submeniscal horizontal out-in repair technique. This
      technique is cheap, safe and has the advantage of avoiding chondral abrasion
      caused by solid implants and suture materials placed over the meniscus.

PMID- 26213702
TI  - Hardware Removal Due to Infection after Open Reduction and Internal Fixation:
      Trends and Predictors.
AB  - BACKGROUND: Little is known about trends and predictors of hardware related
      infection following open reduction and internal fixation (ORIF) of extremity
      fractures, one of the major causes of failure following ORIF. The present study
      was designed and conducted to determine trends and predictors of infection
      related hardware removal following ORIF of extremities using a nationally
      representative database. METHODS: We used Nationwide Inpatient Sample data from
      2002 to 2011 to identify cases of ORIF following upper and lower extremity
      fractures, as well as cases that underwent infection-related hardware removal
      following ORIF. Multivariate analysis was performed to identify independent
      predictors of infection-related hardware removal, controlling for patient
      demographics and comorbidities, hospital characteristics, site of fracture, and
      year. RESULTS: For all ORIF procedures, the highest rate of hardware removal
      related to infection was observed in tarsal fractures (5.56%), followed by tibial
      (3.65%) and carpal (3.37%) fractures. Hardware removal rates due to infection
      increased in all fractures except radial/ulnar fractures. Tarsal fractures(odds
      ratio (OR)=1.06, 95% confidence interval (CI): 1.04-1.09, P<0.001), tibial
      fractures (OR=1.04, 95% CI: 1.03-1.06, P<0.001) and those patients with diabetes
      mellitus (OR=2.64, 95% CI: 2.46-2.84, P<0.001), liver disease (OR=2.04, 95% CI:
      1.84- 2.26, P<0.001), and rheumatoid arthritis (OR=2.06, 95% CI: 1.88-2.25
      P<0.001) were the main predictors of infection-related removals; females were
      less likely to undergo removal due to infection (OR= 0.61, 95% CI: 0.59-0.63
      P<0.001). CONCLUSIONS: Hardware removal rates due to infection increased in all
      fractures except radial/ulnar fractures. Diabetes, liver disease, and rheumatoid
      arthritis were important predictors of infection-related hardware removal. The
      study identified some risk factors for hardwarerelated infection following ORIF,
      such as diabetes, liver disease, and rheumatoid arthritis, that should be studied
      further in an attempt to implement strategies to reduce rate of infection
      following ORIF.

PMID- 26213703
TI  - Effectiveness of the Gastrocsoleous Flap for Coverage of Soft Tissue Defects in
      Leg with Emphasis on the Distal Third.
AB  - BACKGROUND: The standard methods for reconstruction of soft tissue defects in the
      leg include gastrocnemius flap for proximal third defects, soleus flap for middle
      third and free flap in the distal third. However, there are problems with the use
      of free flap, like increased operative time, damage of major vessels and the need
      for experienced microsurgeon. METHODS: This prospective study was undertaken on
      23 patients (20 male and 3 female) with the mean age 32.13 years (14 to 65). This
      group consisted of all of the patients referred to Dr Bahonar Hospital, Kerman
      with soft tissue defects between April 2011 and April 20012 and would give
      informed consent for participation in the study and treatment of the defect with
      muscle flaps. 8 patients with proximal third defects were treated with were
      treated with gastrocnemius flap, 4 with middle third defects with soleus flap and
      3 with reverse soleus flap and 8 with distal third defects with reverse soleus
      flap. The patients were followed up for at least 1 year. Finally the results were
      analyzed by SPSS 16. RESULTS: In patients with soft tissue defect in proximal and
      middle third of leg repair was successful in all. In 5 patients with soft tissue
      defect in distal third of leg repair was complete but in 3 of them flap failure
      was seen. Overall success rate for reverse soleous flap was 72.7%. CONCLUSION:
      The success rate of the flap for the upper and lower thirds was similar to other
      studies and seems that this is the standard method. In the distal third defects
      the reverse soleous flap failed in 3 cases and it seems that preoperative
      investigations such as angiography must be performed before embarking on such a
      procedure.

PMID- 26213704
TI  - Factors Associated with Operative Treatment of De Quervain Tendinopathy.
AB  - BACKGROUND: Geographic and doctor-to-doctor variations in care are a focus of
      quality and safety efforts in medicine. This study addresses factors associated
      with variation in the rate of operative treatment of de Quervain tendinopathy.
      METHODS: We used a database including all patient encounters at 2 large medical
      centers, to study the experience of 10 hand surgeons and 1 physiatrist working in
      a hand surgery office in the treatment of 2,513 patients with de Quervain
      tendinopathy over a 12-year period. Survival analysis using the Kaplan-Meier
      method was used to compare surgery rates and time to surgery. Cox multivariable
      regression analysis was applied to identify factors associated with operative
      treatment. RESULTS: One hundred ninety nine (7.9%) patients had surgery. The odds
      of operative treatment were 1.7 times greater after corticosteroid injection and
      varied more than 10-fold among providers. There was substantial variation in the
      overall rate of surgery by provider. Corticosteroid injection delayed surgery
      slightly, but was associated with a higher rate of surgery. CONCLUSION: Providers
      have substantial influence on treatment of de Quervain tendinopathy. The use of
      decision aids and other methods that help involve the patient in decision-making
      merit investigation as interventions to help reduce doctor-to-doctor variation.

PMID- 26213705
TI  - Pedicle Subtraction Osteotomy in a 5-Year-Old Child with Congenital Kyphosis.
AB  - Vertebral anomalies may also distort the normal regional or global spinal
      alignment and necessitate some therapeutic interventions. Hemiepiphysiodesis is a
      traditional procedure usually described for these young patients but in more
      severe cases some type of osteotomy seems to be necessary. In this technical
      note, we describe a 5-year-old boy with failed previous hemiepiphysiodesis
      surgery, who was successfully treated with one level pedicle subtraction
      osteotomy. This procedure not only corrects the kyphotic deformity at the time of
      the procedure (not relying on future spinal growth), but also avoids more
      hazardous anterior approach. 

PMID- 26213706
TI  - Short-Term Clinical Outcomes of Radial Shortening Osteotomy and Capitates
      Shortening Osteotomy in Kienbock Disease.
AB  - BACKGROUND: There is no consensus on the best surgical treatment in Kienbock
      disease. We compared the short-term outcomes of radial shortening osteotomy and
      capitate shortening osteotomy in patients affected with this disease. METHODS: In
      a retrospective study of 21 patients with Lichtman stage IIIA of Kienbock
      disease, 12 patients with an average follow up of 3.2 +/- 0.6 years had radial
      shortening osteotomy (group I) and 9 patients with an average follow up of 3.1 +/
      0.7 years had capitate shortening osteotomy (group II). The two groups were
      comparable in age, sex, operated side, initial Lichtman stage, and follow-up
      duration. At the last follow-up the patients were evaluated for pain, wrist range
      of motion, grip strength, wrist functional status and change in their Lichtman
      stage. The overall results were evaluated by the Cooney wrist function score and
      DASH score. RESULTS: All the patients in the two groups had improvement of their
      wrist pains. According to the Cooney wrist function score group I had 1
      excellent, 9 good, and 2 fair scores and group II had 1 excellent, 6 good, and 2
      fair scores. Comparisons between the means of pain VAS scores, wrist range of
      movement, grip strength, DASH score, and Cooney wrist function score in the two
      groups were not significant. Also, the changes of the Lichtman stage in the two
      groups were not significant. CONCLUSIONS: Both groups had reasonable short-term
      outcomes. We were unable to recognize a substantial clinical difference between
      the two surgical treatments in short-term outcomes.

PMID- 26213707
TI  - Hip Arthroplasty and its Revision in a Child: Case Report and Literature Review.
AB  - Juvenile idiopathic arthritis is the leading cause of hip replacement in young
      children. However, arthroplasty in this population is challenging with several
      concerns about quality of the growing bone, young age for revision surgery, and
      difficulties in potential several revisions. In this study we introduce a case of
      a 12-year old who is one of the youngest patients to undergo revision hip
      arthroplasty. The index operation was done as a hybrid replacement, cemented for
      stem and press fit for acetabular component. Two years later revision was done
      with severe femoral deficiency. This second procedure was challenging but with
      short-term promising results. So we reviewed the literature for arthroplasty in
      this young population regarding recent findings and trends. According to the
      literature survival of the prosthesis is longer with a cemented acetabular
      component and press fit stem; however, there are evidences that show poor outcome
      of joint replacement after the first revision in juvenile idiopathic arthritis
      patients. 

PMID- 26213708
TI  - Overlapped Pubic Symphysis; a Case Report and Review of the Literature.
AB  - Overlapped pubic symphysis is a rare but serious pelvic injury. This study
      presents a case of overlapped dislocation of the pubic symphysis. He was managed
      by closed reduction under general anesthesia. The patient had urethral trans
      section. At the latest follow up, seven months post injury; he was able to walk
      well without any pelvic pain. However, his urologic problems were continued. We
      also reviewed the literature and analyzed the data of the previous reports as
      well as the current case collectively. The two terms of "locked pubic symphysis"
      and "overlapped pubic symphysis" have been used synonymously in the literature.
      Overlapped pubic symphysis is commonly associated with fracture of the sacrum and
      urethral injury in the male patients. After closed or open reduction, if pelvic
      instability persists, it needs anterior and may posterior internal fixation to
      achieve a stable pelvis. 

PMID- 26213709
TI  - Femoral Condyle Fracture during Anterior Cruciate Ligament Reconstruction.

PMID- 26213710
TI  - Relationship of Edentulism, Sleep Disordered Breathing and Cardiovascular
      Disease: NHANES, 2007-2008.
AB  - BACKGROUND: Edentulism, though declining in younger adults, remains prevalent in
      the U.S. older adult population. Poorer health outcomes, including cardiovascular
      outcomes have been associated with edentulism. Sleep disorders are also common in
      older adults and have been associated with cardiovascular disease. The purpose of
      this study is to determine if edentulism is associated with cardiovascular
      disease when sleep disorders are included in the analyses. METHODS: Data from the
      National Health and Nutrition Examination Survey, 2007-2008 were used in this
      study. Adjusted logistic regression analyses were performed with cardiovascular
      disease as the dependent variable and dental status (edentulism, dentate) as the
      key independent variable and sleep variables introduced as potential confounders.
      RESULTS: In multivariable analyses, edentulism was independently associated with
      cardiovascular disease with an adjusted odds ratio of 2.15 (95% CI: 1.54, 3.00).
      The model included a sleep summary variable, race, sex, education, smoking
      status, and drinking status, physical activity, body mass index, conditions or
      disease count, family poverty index, and insurance status. CONCLUSIONS:
      Edentulism was associated with cardiovascular disease independent of sleep
      disordered breathing.

PMID- 26213711
TI  - Social Determinants and Health Behaviors: Conceptual Frames and Empirical
      Advances.
AB  - Health behaviors shape health and well-being in individuals and populations.
      Drawing on recent research, we review applications of the widely applied "social
      determinants" approach to health behaviors. This approach shifts the lens from
      individual attribution and responsibility to societal organization and the myriad
      institutions, structures, inequalities, and ideologies undergirding health
      behaviors. Recent scholarship integrates a social determinants perspective with
      biosocial approaches to health behavior dynamics. Empirical advances model
      feedback among social, psychological and biological factors. Health behaviors are
      increasingly recognized as multidimensional and embedded in health lifestyles,
      varying over the life course and across place and reflecting dialectic between
      structure and agency that necessitates situating individuals in context. Advances
      in measuring and modeling health behaviors promise to enhance representations of
      this complexity.

PMID- 26213712
TI  - Dysregulated intrahepatic CD4+ T-cell activation drives liver inflammation in
      ileitis-prone SAMP1/YitFc mice.
AB  - BACKGROUND AND AIMS: Liver inflammation is a common extraintestinal manifestation
      of inflammatory bowel disease (IBD); however, whether liver involvement is a
      consequence of a primary intestinal defect or results from alternative pathogenic
      processes remains unclear. Therefore, we sought to determine the potential
      pathogenic mechanism(s) of concomitant liver inflammation in an established
      murine model of IBD. METHODS: Liver inflammation and immune cell subsets were
      characterized in ileitis-prone SAMP1/YitFc (SAMP) and AKR/J (AKR) control mice,
      lymphocyte-depleted SAMP (SAMPxRag-1-/-), and immunodeficient SCID recipient mice
      receiving SAMP or AKR donor CD4+ T-cells. Proliferation and suppressive capacity
      of CD4+ T-effector (Teff) and T-regulatory (Treg) cells from gut-associated
      lymphoid tissue (GALT) and livers of SAMP and AKR mice were measured. RESULTS:
      Surprisingly, prominent inflammation was detected in 4-wk-old SAMP livers, prior
      to histologic evidence of ileitis, while both disease phenotypes were absent in
      age-matched AKRs. SAMP liver disease was characterized by abundant infiltration
      of lymphocytes, required for hepatic inflammation to occur, a Th1-skewed
      environment, and phenotypically-activated CD4+ T-cells. SAMP intrahepatic CD4+ T
      cells also had the ability to induce liver and ileal inflammation when adoptively
      transferred into SCID recipients, whereas GALT-derived CD4+ T-cells produced
      milder ileitis, but not liver inflammation. Interestingly, SAMP intrahepatic CD4+
      Teff cells showed increased proliferation compared to both SAMP GALT- and AKR
      liver-derived CD4+ Teff cells, while SAMP intrahepatic Tregs were decreased among
      CD4+ T-cells and impaired in in vitro suppressive function compared to AKR.
      CONCLUSIONS: Activated intrahepatic CD4+ T-cells induce liver inflammation and
      contribute to experimental ileitis via locally-impaired hepatic immunosuppressive
      function.

PMID- 26213714
TI  - Autonomic Function is Associated with Fitness Level in HIV-Infected Individuals.
AB  - BACKGROUND: Cardiovascular fitness can improve autonomic function (AF) in human
      immunodeficiency virus (HIV)-infected individuals. METHODS: Cross-sectional study
      investigating relationship between AF and cardiovascular fitness in HIV+
      individuals on antiretroviral therapy. Participants' (n=29) maximal oxygen
      consumption (VO2MAX) were assessed by graded exercise test and scaled
      allometrically, then divided into tertiles by fitness level (Unfit, Low-fit, and
      Moderately-fit). Heart rate variability (HRV) and the Autonomic Reflex Screen
      were used to assess AF. RESULTS: Median VO2MAX were 104.9, 130.5, and 150.2 mL*kg
      .67*min-1 for Unfit (n=10), Low-fit (n=10), and Moderately-fit (n= 9) groups
      respectively (p<0.05). Positive correlations were found between VO2MAX and HRV
      (Spearman's rho range 0.383 to 0.553) were found. Quantitative Sudomotor Axon
      Reflex Test (QSART) Distal Leg volumes was lower in Unfit compared to Low-fit
      (p=0.007) and Moderately-fit groups (p=0.018). Unfit QSART total volumes was
      lower than Moderately-fit (p=0.014). CONCLUSION: A positive relationship existed
      between AF and fitness levels. HIV+ individuals could benefit from improved
      fitness.

PMID- 26213713
TI  - Hypoxia Inducible Factor-1alpha in Astrocytes and/or Myeloid Cells Is Not
      Required for the Development of Autoimmune Demyelinating Disease
AB  - Hypoxia-like tissue alterations, characterized by the upregulation of hypoxia
      inducible factor-1alpha (HIF-1alpha), have been described in the normal appearing
      white matter and pre-demyelinating lesions of multiple sclerosis (MS) patients.
      As HIF-1alpha regulates the transcription of a wide set of genes involved in
      neuroprotection and neuroinflammation, HIF-1alpha expression may contribute to
      the pathogenesis of inflammatory demyelination. To test this hypothesis, we
      analyzed the effect of cell-specific genetic ablation or overexpression of HIF
      1alpha on the onset and progression of experimental autoimmune encephalomyelitis
      (EAE), a mouse model for MS. HIF-1alpha was mainly expressed in astrocytes and
      microglia/macrophages in the mouse spinal cord at the peak of EAE. However,
      genetic ablation of HIF-1alpha in astrocytes and/or myeloid cells did not
      ameliorate clinical symptoms. Furthermore, conditional knock-out of Von Hippel
      Lindau, a negative regulator of HIF-1alpha stabilization, failed to exacerbate
      the clinical course of EAE. In accordance with clinical symptoms, genetic
      ablation or overexpression of HIF-1alpha did not change the extent of spinal cord
      inflammation and demyelination. Overall, our data indicate that despite dramatic
      upregulation of HIF-1alpha in astrocytes and myeloid cells in EAE, HIF-1alpha
      expression in these two cell types is not required for the development of
      inflammatory demyelination. Despite numerous reports indicating HIF-1alpha
      expression in glia, neurons, and inflammatory cells in the CNS of MS patients,
      the cell-specific contribution of HIF-1alpha to disease pathogenesis remains
      unclear. Here we show that although HIF-1alpha is dramatically upregulated in
      astrocytes and myeloid cells in EAE, cell-specific depletion of HIF-1alpha in
      these two cell types surprisingly does not affect the development of
      neuroinflammatory disease. Together with two recently published studies showing a
      role for oligodendrocyte-specific HIF-1alpha in myelination and T-cell-specific
      HIF-1alpha in EAE, our results demonstrate a tightly regulated cellular
      specificity for HIF-1alpha contribution in nervous system pathogenesis.

PMID- 26213715
TI  - Colonization and Persistence of Labeled and "Foreign" Strains of Aggregatibacter
      actinomycetemcomitans Inoculated into the Mouths of Rhesus Monkeys.
AB  - Aggregatibacter actinomycetemcomitans (Aa) is a pathobiont and part of a
      consortium of bacteria that can lead to periodontitis in humans. Our aim was to
      develop a model for oral inoculation of labeled Aa into a suitable host in order
      to study Aa traits and ecological factors that either enhance or repress its
      persistence. Primate species were screened for Aa to select a host for
      colonization studies. Macaca mulatta (Rhesus/Rh) was selected. Rh Aa strains were
      isolated, subjected to sequencing and functional analysis for comparison to human
      strains. "Best" methods for microbial decontamination prior to inoculation were
      assessed. Three groups were studied; Group 1 (N=5) was inoculated with Aa
      Spectinomycin resistant (SpecR) Rh strain 4.35, Group 2 (N=5) inoculated with Aa
      SpecR human strain IDH 781, and Group 3 (N=5) the un-inoculated control. Repeated
      feeding with pancakes spiked with SpecRAa followed high dose oral inoculation.
      Cheek, tongue, and plaque samples collected at baseline 1, 2, 3, and 4 weeks
      after inoculation were plated on agar; 1) selective for Aa, 2) enriched for total
      counts, and 3) containing 50 ug/ml of Spec. Aa was identified by colonial
      morphology and DNA analysis. Rh and human Aa had > 93-98 % genome identity. Rh Aa
      attached to tissues better than IDH 781 in vitro (p < 0.05). SpecR IDH 781 was
      not recovered from any tissue at any time; whereas, RhSpecR 4.35 was detected in
      plaque, but never tongue or cheek, in all monkeys at all times (> 1 * 105
      colonies/ml; p < 0.001). In conclusion, the primate model provides a useful
      platform for studying integration of Aa strains into a reduced but established
      oral habitat. Primate derived SpecRAa was consistently detected in plaque at all
      collection periods; however, human derived Aa was never detected. The model
      demonstrated both microbial as well as tissue specificity.

PMID- 26213716
TI  - Serpine1 Mediates Porphyromonas gingivalis Induced Insulin Secretion in the
      Pancreatic Beta Cell Line MIN6.
AB  - Periodontitis is an inflammatory disease resulting in destruction of gingiva and
      alveolar bone caused by an exuberant host immunological response to periodontal
      pathogens. Results from a number of epidemiological studies indicate a close
      association between diabetes and periodontitis. Results from cross-sectional
      studies indicate that subjects with periodontitis have a higher odds ratio of
      developing insulin resistance (IR). However, the mechanisms by which
      periodontitis influences the development of diabetes are not known. Results from
      our previous studies using an animal model of periodontitis suggest that
      periodontitis accelerates the onset of hyperinsulinemia and IR. In addition, LPS
      from a periodontal pathogen, Porphyromonas gingivalis (Pg), stimulates Serpine1
      expression in the pancreatic beta cell line MIN6. Based on these observations, we
      hypothesized that a periodontal pathogen induces hyperinsulinemia and Serpine1
      may be involved in this process. To test this hypothesis, we co-incubated Pg with
      the pancreatic beta cell line MIN6 and measured the effect on insulin secretion
      by MIN6 cells. We further determined the involvement of Serpine1 in insulin
      secretion by downregulating Serpine1 expression. Our results indicated that Pg
      stimulated insulin secretion by approximately 3.0 fold under normoglycemic
      conditions. In a hyperglycemic state, Pg increased insulin secretion by 1.5 fold.
      Pg significantly upregulated expression of the Serpine1 gene and this was
      associated with increased secretion of insulin by MIN6 cells. However, cells with
      downregulated Serpine1 expression were resistant to Pg stimulated insulin
      secretion under normoglycemic conditions. We conclude that the periodontal
      pathogen, Pg, induced insulin secretion by MIN6 cells and this induction was, in
      part, Serpine1 dependent. Thus, Serpine1 may play a pivotal role in insulin
      secretion during the accelerated development of hyperinsulinemia and the
      resulting IR in the setting of periodontitis.

PMID- 26213717
TI  - Cuff-Free Blood Pressure Estimation Using Pulse Transit Time and Heart Rate.
AB  - It has been reported that the pulse transit time (PTT), the interval between the
      peak of the R-wave in electrocardiogram (ECG) and the fingertip
      photoplethysmogram (PPG), is related to arterial stiffness, and can be used to
      estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP).
      This phenomenon has been used as the basis to design portable systems for
      continuously cuff-less blood pressure measurement, benefiting numerous people
      with heart conditions. However, the PTT-based blood pressure estimation may not
      be sufficiently accurate because the regulation of blood pressure within the
      human body is a complex, multivariate physiological process. Considering the
      negative feedback mechanism in the blood pressure control, we introduce the heart
      rate (HR) and the blood pressure estimate in the previous step to obtain the
      current estimate. We validate this method using a clinical database. Our results
      show that the PTT, HR and previous estimate reduce the estimated error
      significantly when compared to the conventional PTT estimation approach (p<0.05).

PMID- 26213718
TI  - Landmark-Based Indoor Positioning for Visually Impaired Individuals.
AB  - Position localization is essential for visually impaired individuals to live
      independently. Comparing with outdoor environment in which the global positioning
      system (GPS) can be utilized, indoor positioning is more difficult due to the
      absence of the GPS signal and complex or unfamiliar building structure. In this
      paper, a novel landmark-based assistive system is presented for indoor
      positioning. Our preliminary tests in several buildings indicate that this system
      can provide accurate indoor location information.

PMID- 26213719
TI  - A Feasibility Study on a Single-Unit Wireless EEG Sensor.
AB  - The electroencephalography (EEG) is a widely used diagnostic tool for a number of
      clinical applications, such as diagnosis of epilepsy and study of sleep.
      Traditionally, to acquire a single channel of EEG signal, at least three
      electrodes must be installed on the skin separated at certain distances. They
      must also be connected to an amplifier by electrode leads. These basic
      requirements are acceptable in most clinical laboratories, but are unacceptable
      in certain point-of-care applications, such as during patient transportation. In
      order to remove these requirements, we are designing a single-unit EEG sensor in
      the size of a U.S. penny. It contains multiple closely spaced dry electrodes that
      can hook onto the skin, an electronic circuitry for signal amplification,
      digitization and wireless transmission, and a battery providing power. In this
      paper, we answer two key questions regarding the feasibility of the single-unit
      design: 1) can the closely-spaced electrodes obtain EEG signal reliably? and 2)
      will the electrodes orientated in certain ways improve signal quality? We
      conducted experiments utilizing closely spaced electrodes to record the alpha
      wave in the EEG. Our results have shown positive answers to the two feasibility
      questions.

PMID- 26213720
TI  - A Method for Automated Cortical Surface Registration and Labeling.
AB  - Registration and delineation of anatomical features in MRI of the human brain
      play an important role in the investigation of brain development and disease.
      Accurate, automatic and computationally efficient cortical surface registration
      and delineation of surface-based landmarks, including regions of interest (ROIs)
      and sulcal curves (sulci), remain challenging problems due to substantial
      variation in the shapes of these features across populations. We present a method
      that performs a fast and accurate registration, labeling and sulcal delineation
      of brain images. The new method presented in this paper uses a multiresolution,
      curvature based approach to perform a registration of a subject brain surface
      model to a delineated atlas surface model; the atlas ROIs and sulcal curves are
      then mapped to the subject brain surface. A geodesic curvature flow on the
      cortical surface is then used to refine the locations of the sulcal curves sulci
      and label boundaries further, such that they follow the true sulcal fundi more
      closely. The flow is formulated using a level set based method on the cortical
      surface, which represents the curves as zero level sets. We also incorporate a
      curvature based weighting that drives the curves to the bottoms of the sulcal
      valleys in the cortical folds. Finally, we validate our new approach by comparing
      sets of automatically delineated sulcal curves it produced to corresponding sets
      of manually delineated sulcal curves. Our results indicate that the proposed
      method is able to find these landmarks accurately.

PMID- 26213721
TI  - Weak aurophilic interactions in a series of Au(III) double salts.
AB  - In this work, several new examples of rare Au(III)Au(III) aurophilic contacts are
      reported. A series of gold(iii) double salts and complexes, viz. [AuX2(L)][AuX4]
      (L = 2,2'-bipyridyl, X = Cl , Br ; L = 2,2'-bipyrimidine, X = Cl , Br ; L = 2,2'
      dipyridylamine, X = Cl , Br ), [AuX3(biq)] (biq = 2,2'-biquinoline, X = Cl , Br
      ), [LH][AuX4] (L = 2,2'-bipyridyl, X = Cl ; L = 2,2'-bipyrimidine, X = Cl ; L =
      2,2'-dipyridylamine, X = Cl , Br ; L = 2,2'-biquinoline, X = Cl , Br ),
      [AuBr2(bpy)]2[AuBr4][AuBr2] , [AuCl2(bpm)][AuCl2] , (bpmH)2[AuBr4][AuBr2] , and
      (dpaH)[AuBr2] (, , and were reported earlier) was synthesized by coordination of
      a particular ligand to the Au(III) center and subsequent reduction of the formed
      product with acetone. Inspection of the X-ray structural data for , , and
      indicates that the Au(III) metal centers approach each other closer than the sum
      of their van der Waals radii, thus forming the aurophilic contacts, which were
      confirmed by topological charge density analysis according to the Quantum Theory
      of Atoms in Molecules (QTAIM). In , , and , such contacts are located only
      between the metal centers of the ion pair, whereas in , the aurophilic
      interactions form the cation-anion-anion array, and in , the aurophilicity exists
      between the gold atoms of the cations. It was also demonstrated that the
      interatomic distance alone is not a reliable measure of the aurophilic
      interactions, at least at the weakest limit of the interaction strength, and it
      needs to be complemented with structural analysis of the whole molecule and
      computational results. 

PMID- 26213723
TI  - Author Response: Atul Krishnan Ramesh, New  York:.

PMID- 26213722
TI  - Author Response: Andrea J. Boon, Eric J. Sorenson,  Jeffery A. Strommen, James C.
      Watson, Rochester,  MN.

PMID- 26213724
TI  - Preface.

PMID- 26213725
TI  - Author's reply.

PMID- 26213726
TI  - Author's reply.

PMID- 26213727
TI  - Author's Reply.

PMID- 26213728
TI  - Author's Reply.

PMID- 26213729
TI  - Author's Reply.

PMID- 26213730
TI  - Author's Reply.

PMID- 26213731
TI  - Interacting with Diverse Realities.

PMID- 26213732
TI  - Natural User Interfaces for  Adjustable Autonomy in Robot  Control.

PMID- 26213733
TI  - Data-Driven Discoveries: Pushing  Visualization Research Further.

PMID- 26213734
TI  - Dr. Francesco Epifano.

PMID- 26213735
TI  - Preface.

PMID- 26213736
TI  - Guest editorial: special issue micro- and nanomachines.

PMID- 26213737
TI  - Combined Rewarding Mechanisms   Can be Implemented to Incentivize   the Best
      Reviewers.

PMID- 26213738
TI  - Spatial autocorrelation and congruence in the distribution of language and mammal
      richness: a reply to Cardillo et al. (2015).

PMID- 26213739
TI  - Thresholds for impaired species recovery.
AB  - Studies on small and declining populations dominate research in conservation
      biology. This emphasis reflects two overarching frameworks: the small-population
      paradigm focuses on correlates of increased extinction probability; the declining
      population paradigm directs attention to the causes and consequences of
      depletion. Neither, however, particularly informs research on the determinants,
      rate or uncertainty of population increase. By contrast, Allee effects (positive
      associations between population size and realized per capita population growth
      rate, r(realized), a metric of average individual fitness) offer a theoretical
      and empirical basis for identifying numerical and temporal thresholds at which
      recovery is unlikely or uncertain. Following a critique of studies on Allee
      effects, I quantify population-size minima and subsequent trajectories of marine
      fishes that have and have not recovered following threat mitigation. The data
      suggest that threat amelioration, albeit necessary, can be insufficient to effect
      recovery for populations depleted to less than 10% of maximum abundance (N(max)),
      especially when they remain depleted for lengthy periods of time. Comparing
      terrestrial and aquatic vertebrates, life-history analyses suggest that
      population-size thresholds for impaired recovery are likely to be comparatively
      low for marine fishes but high for marine mammals.Articulation of a 'recovering
      population paradigm' would seem warranted. It might stimulate concerted efforts
      to identify generic impaired recovery thresholds across species. It might also
      serve to reduce the confusion of terminology, and the conflation of causes and
      consequences with patterns currently evident in the literature on Allee effects,
      thus strengthening communication among researchers and enhancing the practical
      utility of recovery-oriented research to conservation practitioners and resource
      managers.

PMID- 26213741
TI  - New taxa and distributional notes on Abbottella and related taxa (Gastropoda:
      Littorinoidea: Annulariidae).
AB  - Seven new species of Abbottella and related taxa are described from Hispaniola:
      Abbottella calliotropis n. sp., Abbottella diadema n. sp., Abbottella dichroa n.
      sp., Abbottella nitens n. sp., Abbottella paradoxa n. sp., Abbottella tenebrosa
      n. sp., and Leiabbottella thompsoni n. sp. Distributional and habitat notes are
      given for additional taxa.

PMID- 26213740
TI  - Two functional types of attachment pads on a single foot in the Namibia bush
      cricket Acanthoproctus diadematus (Orthoptera: Tettigoniidae).
AB  - Insects have developed different structures to adhere to surfaces. Most common
      are smooth and hairy attachment pads, while nubby pads have also been described
      for representatives of Mantophasmatodea, Phasmida and Plecoptera. Here we report
      on the unusual combination of nubby and smooth tarsal attachment structures in
      the !nara cricket Acanthoproctus diadematus. Their three proximal tarsal pads
      (euplantulae) have a nubby surface, whereas the most distal euplantula is rather
      smooth with a hexagonal ground pattern resembling that described for the great
      green bush-cricket Tettigonia viridissima. This is, to our knowledge, the first
      report on nubby euplantulae in Orthoptera and the co-occurrence of nubby and
      smooth euplantulae on a single tarsus in a polyneopteran species. When adhering
      upside down to a horizontal glass plate, A. diadematus attaches its nubby
      euplantulae less often, compared to situations in which the animal is hanging
      upright or head down on a vertical plate. We discuss possible reasons for this
      kind of clinging behaviour, such as morphological constrains, the different role
      of normal and shear forces in attachment enhancement of the nubby and smooth
      pads, ease of the detachment process, and adaptations to walking on cylindrical
      substrates.

PMID- 26213742
TI  - Description of three females of the genus Acanthagrion (Odonata: Coenagrionidae)
      with a key to the females of Argentina.
AB  - The neotropical genus Acanthagrion Selys (Odonata: Coenagrionidae) is composed of
      44 species, of which the females of 31 species are currently known. In this
      contribution the females of A. aepiolum Tennessen and A. minutum Leonard are
      described and that of A. ascendens Calvert is redescribed. Distribution maps and
      new records are provided for all three species. Finally, a key to females of the
      genus Acanthagrion from Argentina is provided.

PMID- 26213743
TI  - A new species and new records of Gymnolaelaps Berlese from Iran (Acari:
      Laelapidae), with a review of the species occurring in the Western Palaearctic
      Region.
AB  - This paper reports on five species of mites of the genus Gymnolaelaps associated
      with ants and soil in Iran--G. artavilensis sp. nov. from Pheidole pallidula, G.
      laevis (Michael) and G. myrmecophilus (Berlese) from Tetramorium caespitum, G.
      myrmophila (Michael) from Formica sp., and G obscuroides Costa from soil.
      Gymnolaelaps australicus Womersley and G. hospes (Berlese) have also been
      reported from Iran, in association with P. pallidula, but those records are
      incorrect. A key to the species of Gymnolaelaps occurring in the Western
      Palaearctic Region is presented. We review the related genus Laelaspisella Marais
      & Loots, and transfer Gymnolaelaps kabitae Bhattacharyya and G. canestrinii
      (Berlese) sensu Costa to Laelaspisella.

PMID- 26213744
TI  - Review of Scirtidae (Coleoptera: Scirtoidea) described by Johan Christian
      Fabricius (1745-1808).
AB  - Scirtidae described by J. Ch. Fabricius are listed. Poorly known South American
      and Indian species are redescribed, illustrated and figured. Cyphon depressus
      Fabricius is transferred to Ora Clark, and Cistela livida Fabricius is
      transferred to Pseudomicrocara Armstrong. Ora complanata (Guerin-Meneville) is
      probably a junior synonym of Ora depressa (Fabricius). Data on Scirtidae
      collections studied by Fabricius are summarized.

PMID- 26213745
TI  - Geoparnus loebli, a new species of terrestrial dryopid from Peninsular Malaysia
      (Coleoptera: Dryopidae).
AB  - Three species have been recognized in the genus Geoparnus Besuchet, 1978, all
      collected by sifting ground debris from tropical rainforests of Malaysia. The new
      species Geoparnus loebli sp. nov. is described; morphological similarities to
      known species G setifer Besuchet, 1978 and G rhinoceros Kodada, Jach, Ciampor Jr
      & (Camporova-Zat'ovicova, 2007 are discussed. Habitus of adult, male and female
      genitalia as well as other diagnostic characters are illustrated.

PMID- 26213747
TI  - A new species of Lasianobia Hampson, 1905 (Lepidoptera, Noctuinae) from China.

PMID- 26213746
TI  - Three new earthworm species of the genus Amynthas (Clitellata: Megascolecidae)
      from Mt. Chiak National Park, Korea.
AB  - Earthworm specimens collected from Mt. Chiak, National Park, Korea were found to
      represent three new species of megascolecid earthworms: Amynthas chiakensis sp.
      nov., Amynthas gyeongriae sp. nov., and Amynthas wonjuensis sp. nov. Amynthas
      chiakensis sp. nov. has two pairs of spermathecae in VII and VIII, small
      transverse oval male porophores each with C-shaped small patches of genital
      papillae, 0.22-0.31 circumference apart. Amynthas gyeongriae sp. nov. has
      spermathecae in VI-VIII, male field with large circular-shaped raised pads and
      seminal grooves, with pores 0.16-0.28 circumference apart. Amynthas wonjuensis
      sp. nov. has spermathecae in VI and VII, male pores superficial in XVIII on small
      oval-shaped white porophores lateral to large roughly circular raised genital
      papillae, 0.15 circumference apart.

PMID- 26213748
TI  - The genus Neoanthrenus Armstrong, 1941 (Coleoptera: Dermestidae: Anthrenini): A
      new synonym of Anthrenus Geoffroy, 1762.
AB  - A new synonym is proposed for Anthrenus Geoffroy, 1762 (= Neoanthrenus Armstrong,
      1941 syn. n.) and the following species are transferred to Anthrenus (Nathrenus):
      Anthrenus (Nathrenus) armstrongielus replacement name for Neoanthrenus armstrongi
      Kalik, 1957; Anthrenus (Nathrenus) consobrinus (Hava), 2005 new combination;
      Anthrenus (Nathrenus) frater Arrow, 1915 return to former combination; Anthrenus
      (Nathrenus) king (Hava), 2002 new combination; Anthrenus (Nathrenus) macqueeni
      (Armstrong), 1949 new combination; Anthrenus (Nathrenus) niveosparsus
      (Armstrong), 1941 new combination; Anthrenus (Nathrenus) ocellifer Blackburn,
      1891 return to former combination; Anthrenus (Nathrenus) parallelus (Armstrong),
      1941 new combination; and Anthrenus (Nathrenus) svatopluki replacement name for
      Neoanthrenus bilyi Hava, 2003b.

PMID- 26213749
TI  - Nomenclatural and bibliographic corrections to the Catalog of Nabidae (Hemiptera:
      Heteroptera) for the Neotropical Region.
AB  - The recent catalog of Neotropical Nabidae is corrected and updated. Synonymies,
      species, and references that were overlooked are now included. 11 genera and 83
      species are presently known from this region.

PMID- 26213750
TI  - First record of Latris lineata (Forster, 1801) in the Southwest Atlantic Ocean.

PMID- 26213751
TI  - Review of Xenochironomus Kieffer, 1921 (Diptera: Chironomidae) with description
      of six new species.
AB  - The genus Xenochironomus Kieffer is reviewed. Five new species are described from
      Brazil, X. alaidae, X. amazonensis and X. martini as male; X. grini and X.
      mendesi as male, pupa and larva, and X. ethiopensis from Ethiopia is described as
      adult male. X. canterburyensis (Freeman) is redescribed as male, pupa and larva;
      X. trochanteratus (Thompson), X. trisetosus (Kieffer), X. ugandae (Goetghebuer)
      and X. tuberosus Wang as males; notes on X. xenolabis (Kieffer), X. flaviventris
      (Kieffer), X. longicrus (Kieffer), X. lacertus Dutta et Chaudhuri and X. ceciliae
      Roque et Trivinho-Strixino are also given. The species X. nigricaudus Hashimoto
      is recognized as nomen dubium. Keys to males, pupae and larvae are presented.

PMID- 26213752
TI  - A revision of the endemic Chinese genus Cornopsylla (Hemiptera: Psyllidae), with
      potential pests on Zanthoxylum (Rutaceae).
AB  - The endemic Chinese psyllid genus Cornopsylla Li is reviewed with a revised
      generic diagnosis. Cornopsylla zanthoxylae Li and C. trichotoma Li are
      redescribed, and Cornopsylla magna sp. nov. and C. rotundiconis sp. nov. are
      described. Keys to adults and nymphs of this genus are given, and the systematic
      position of Cornopsylla is reviewed. The potential of Cornopsylla spp. as major
      pests on cultivated Zanthoxylum is discussed. Psylla sarcospermae (Li) comb. nov.
      is proposed for this species that does not share the generic characters of
      Cornopsylla.

PMID- 26213753
TI  - New sea anemone (Anthozoa: Actiniaria) from Patagonia: Andvakia manoloi sp. nov.
AB  - A new species of sea anemone from the intertidal zone of San Matias Gulf is
      described. Andvakia manoloi sp. nov. is a small and inconspicuous species that
      differs from other species of the genus in number of tentacles, number of
      mesenteries at proximal and distal part of the column, column division, muscles,
      cnidae, size, habit and distribution. Andvakia manoloi sp. nov. is the first
      species of the genus from South America and the southernmost record of the genus.

PMID- 26213754
TI  - An index to new genera and species of Nematoda in Zootaxa from 2007 to 2012.
AB  - Of 104 papers on nematodes published in Zootaxa from 2007 to 2012, seventy five,
      by 136 authors from 27 countries, described eight new genera and 155 new species.
      A bibliographic analysis of these papers and a list of new genera and species are
      presented in this paper.

PMID- 26213755
TI  - A new species of the hippolytid genus Paralebbeus Bruce & Chace, 1986 (Crustacea:
      Decapoda: Caridea) from the Coral Seamount, southwestern Indian Ocean.
AB  - The hippolytid genus Paralebbeus Bruce & Chace, 1986, is only known from two
      species, P. zotheculatus Bruce & Chace, 1986 (type species) and P. zygius Chace,
      1997. Both are known from the western Pacific, though P zotheculatus was
      originally described from the Australian Northwest Shelf in the Indian Ocean. In
      this paper, a new species, P. mollis, is described and illustrated on the basis
      of a single ovigerous female from the Coral Seamount, southwestern Indian Ocean,
      at a depth of 952 m as the third representative of the genus. The new species is
      readily distinguished from its congeners by the rostrum being armed with one
      tooth on both the dorsal and ventral margin and the conspicuous pterygostomial
      tooth on the carapace. Because of these characteristics of the new species, the
      diagnosis of Paralebbeus is slightly emended. The holotype of P mollis n. sp. was
      associated with an unidentified hexactinellid sponge, like the other two known
      species.

PMID- 26213756
TI  - Revision of Cerozodus Bigot, 1857 (Diptera, Asilidae, Asilinae) with description
      of a new species from Brazil.
AB  - The second species of the Neotropical genus Cerozodus Bigot, 1857, Cerozodus
      brachylobus sp. nov. is described from Mirador, Maranhao state, Brazil and
      Cerozodus nodicornis (Wiedemann, 1828) is redescribed. The habitus, wing and male
      terminalia structures are described and illustrated.

PMID- 26213757
TI  - Notes on the correct taxonomic status of Haliotis rugosa Lamarck, 1822, and
      Haliotis pustulata Reeve, 1846, with description of a new subspecies from
      Rodrigues Island, Mascarene Islands, Indian Ocean (Mollusca: Vetigastropoda:
      Haliotidae).

PMID- 26213758
TI  - On the available names for the northern and eastern South American subspecies of
      Puma concolor (Linnaeus, 1771) (Mammalia: Felidae) and their type localities.

PMID- 26213759
TI  - Haludaria, a replacement generic name for Dravidia (Teleostei: Cyprinidae).

PMID- 26213760
TI  - A New Species of Seed-harvester Ant, Pogonomyrmex hoelldobleri (Hymenoptera:
      Formicidae), from the Mohave and Sonoran Deserts of North America.
AB  - Pogonomyrmex magnacanthus Cole was described as a distinct species; unusually
      large eyes and a high ocular index (maximum eye diameter/head width) were listed
      as diagnostic characters. However, examination of numerous series of P.
      magnacanthus revealed that both characters were highly variable, and that these
      series consisted of P. magnacanthus plus an undescribed species, Pogonomyrmex
      hoelldobleri Johnson, Overson & Moreau sp. nov. This paper describes all three
      castes of P. hoelldobleri as well as the alate queen of P mohavensis, which is
      very similar to that of P. hoelldobleri. A molecular phylogeny that consisted of
      3,703 bp from one mitochondrial and five nuclear gene fragments-supported the
      monophyly of P. hoelldobleri, P. magnacanthus, and P mohavensis. Pogonomyrnex
      inagnacanthus can be separated from other P. californicus group species based on:
      (1) its unusually large eyes, (2) a high ocular index, and (3) a malar ratio that
      is typically < or = 1.0. Pogonomyrmex hoelldobleri can be separated from other P.
      californicus group species based on the combination of: (1) eyes not unusually
      large, (2) cephalic rugae not forming circumocular whorls, but rather converging
      posterior to the eyes, usually near the vertex, (3) mandible with seven teeth,
      and (4) interrugal spaces on pronotal sides moderately to strongly granulate,
      dull to weakly shining. Pogonomyrmex mohavensis can be separated from other P.
      californicus group species based on the combination of: (1) eyes not unusually
      large, (2) cephalic rugae not forming circumocular whorls, but rather extending
      more or less directly to the vertex or converging only slightly near the vertex,
      (3) mandible with six teeth (a seventh sometimes occurs as a denticle between the
      basal and sub-basal teeth), and (4) interrugal spaces on pronotal sides smooth
      and shining to weakly punctate and moderately shining. We also provide field
      observations and distribution maps for P. magnacanthus, P. hoelldobleri, and P.
      mohavensis, and an updated key to P californicus group species that occur in
      central and western North America.

PMID- 26213761
TI  - A new species of Szelenyiopria Fabritius (Hymenoptera: Diapriidae), larval
      parasitoid of Acromyrmex subterraneus subterraneus (Forel) (Hymenoptera:
      Formicidae) from Brazil.
AB  - Szelenyiopria talitae sp. nov. is described and illustrated. This species is
      shown to be a larval parasitoid of Acromynnex subterraneus subterraneus (Forel).

PMID- 26213762
TI  - Distribution of Sipuncula in the Gulf of Valencia and Cape Nao (western
      Mediterranean).
AB  - The present study analyses the distribution and diversity of sipunculan species
      inhabiting soft substrata in the Gulf of Valencia and Cape Nao (western
      Mediterranean) in relation to the characteristics of the sediment. Eighty-seven
      stations in 14 localities were sampled annually from 2004 to 2008. Nine species
      were reported, with Aspidosiphon (Aspidosiphon) muelleri being the dominant
      species in the area and Thysanocardia procera the most widely distributed.
      Pearson correlation coefficient and multivariate analysis showed how sipunculan
      abundances of certain species were related to the sediment characteristics,
      especially grain size. The shell-dwelling species A. (A.) muelleri and Phascolion
      (Phascolion) caupo were dominant in stations with high amount of coarse sand and
      gravel, while Sipunculus (Sipunculus) nudus appeared in stations dominated by
      fine sand with low organic content. Pn. (Pn.) caupo and T procera were reported
      for the first time in the study area. Moreover, it was the second record of Pn.
      (Pn.) caupo for the Mediterranean Sea.

PMID- 26213763
TI  - The identity of Rana margaritifera Laurenti, 1768 (Anura, Bufonidae).
AB  - Rana margaritifera was described by Laurenti in 1768 and currently is associated
      to the genus Rhinella, under the combination Rhinella margaritifera. Currently,
      the R. margaritifera species group consists of 16 recognized species.
      Furthermore, many additional species have been suggested to exist in this group
      which highlights the ambiguity surrounding the identity of Rhinella margaritifera
      and impend further description of the species in this group. After an exhaustive
      bibliographic review, we concluded that the recent designation of a lectotype for
      R. margaritifera is invalid according with Art. 73, ICZN, 1999. Herein, we
      designate and provide the description of a neotype for Rana margaritifera
      Laurenti, 1768.

PMID- 26213764
TI  - Monophyly of the Agoniatinae (Characiformes: Characidae).
AB  - The Characidae is the most diverse family of Neotropical fishes, currently
      encompassing more than one thousand valid species. Some subgroups within this
      family still lack phylogenetic definitions, being diagnosed on the basis of
      combination of characters, a common procedure in pre-cladistic studies.
      Agoniatinae, currently composed by two valid species, Agoniates anchovia and A.
      halecinus, is one of them. In the present study the Agoniatinae is redefined
      using a phylogenetically oriented comparative survey that included the two
      Agoniates species plus 114 species representing all the major clades of the
      Characidae and their closest relatives. Six derived morphological characters are
      identified as synapomorphies for the Agoniatinae: deep notch on the posterior
      region of the maxilla joining the ventral margin of the infraorbital 2;
      dentigerous portion of premaxilla shorter than the ascending process of this
      bone; dentary canine preceded by tricuspid teeth; ventral margin of the urohyal
      markedly convex; base of the uppermost ray of the ventral lobe of the caudal fin
      much expanded, being as deep as the distal margin of hypural 2; and levator arcus
      palatini muscle with a posterodorsal bundle of fibers attaching to the dorsal
      face of the sphenotic spine.

PMID- 26213765
TI  - Taxonomic study on the planthopper genus Macrocixius Matsumura (Hemiptera:
      Fulgoromorpha: Cixiidae) with descriptions of two new species from China.
AB  - The cixiid planthopper genus Macrocixius Matsumura, 1914 (Hemiptera:
      Fulgoromorpha: Cixiidae: Cixiini) is known to from two species: M. giganteus
      Matsumura, 1914 and M. grossus Tsaur & Hsu, 1991 which are redescribed and
      illustrated. Two new species, M. rarimaculatus sp. nov. and M. unispinus sp. nov.
      from south China, are described and illustrated. The generic characteristics are
      redefined and a key to the species is provided.

PMID- 26213766
TI  - A new species of the genus Opisthotropis Gunther, 1872 (Squamata: Colubridae:
      Natricinae) from Guangdong Province, China.
AB  - A new natricid snake of the genus Opisthotropis Gunther, 1872, Opisthotropis laui
      sp. nov., is described from Mt. Gudou, Jiangmen City, Guangdong Province, China.
      The new species can be distinguished from other congeners by the combination of
      the following characters: dorsal scales weakly keeled throughout, in 25:23:23
      rows; 10 supralabials; 11 infralabials; two internasals, longer than wide, not
      touching the loreal; one loreal, not touching the eye; one preocular; two
      postoculars; one anterior temporal scale; 152 ventrals; 53 subcaudals; body and
      tail dark olive above, with light yellow crossbars.

PMID- 26213767
TI  - A new species of Quwatanabius Smetana (Coleoptera, Staphylinidae, Staphylininae)
      from Guangxi, South China.
AB  - A new species of Quwatanabius Smetana, Q. dayaoensis Hu, Li & Zhao sp. n. from
      Dayao Mountain, Guangxi Province, China, is described and illustrated. An
      identification key to species of Quwatanabius is provided.

PMID- 26213768
TI  - Descriptions of ten known species of the superfamily Mononchoidea (Mononchida:
      Nematoda) from North India with a detailed account on their variations.
AB  - Ten species of the superfamily Mononchoidea from fourteen populations collected
      during a survey of terrestrial and freshwater habitats of North India, are
      described and illustrated. The species include Clarkus papillatus (Bastian, 1865)
      Jairajpuri, 1970, Prionchulus muscorum (Dujardin, 1845) Wu & Hoeppli, 1929,
      Mylonchulus contractus Jairajpuri, 1970, M. hawaiiensis (Cassidy, 1931) Andrassy,
      1958, M. lacustris (Cobb in Cobb, 1915) Andrdssy, 1958, M. minor (Cobb, 1893)
      Andrassy, 1958, M. obtusicaudatus (Daday, 1899) AndrAssy, 1958, M. vasis Yeates,
      1992, Sporonchulus ibitiensis (Carvalho, 1951) Andrassy, 1958 and S. vagabundus
      Jairajpuri, 1971. Mylonchulus vasis Yeates, 1992 is reported for the first time
      from India. The variable, as well as the relatively consistent characters are
      discussed in different populations to assess their role in the diagnosis of
      species.

PMID- 26213769
TI  - A new species of Duttaphrynus (Anura:Bufonidae) from Northeast India.
AB  - A new species of montane toad Duttaphrynus is described from Nagaland state of
      Northeast India. The new species is diagnosable based on following combination of
      characters: absence of preorbital, postorbital and orbitotympanic ridges,
      elongated and broad parotid gland, first finger longer than second and presence
      of a mid-dorsal line. The tympanum is hidden under a skin fold (in male) or
      absent (in female). The species is compared with its congers from India and Indo
      China. We propose to consider Duttaphrynus wokhaensis as junior synonym of
      Duttaphrynus melanostictus.

PMID- 26213770
TI  - Eriophyes species (Acari: Eriophyoidea) inhabiting lime trees (Tilia spp.:
      Tiliaceae)--supplementary description and morphological variability related to
      host plants and female forms.
AB  - Three poorly known species of the subfamily Eriophyinae living on Tilia spp.
      (Tiliaceae) are illustrated and supplementary descriptions are provided. Two of
      them, Eriophyes exilis (Nalepa 1892) and Eriophyes nervalis (Nalepa 1918), were
      recorded both in vein angle galls on leaves of Tilia platyphyllos Scop. and in
      erinea on leaves of Tilia tomentosa Moench, Tilia americana L. 'Moltkei', Tilia
      americana var. heterophylla (Vent.) Loudon, Tilia cordata Mill., Tiliajaponica
      (Miq.) Simonk., Tilia petiolaris DC. and Tilia zamoyskiana Wr6bl. The third
      species, Eriophyes tiliae Nalepa 1890, was found in nail galls on leaves of T
      platyphyllos, T americana and T. cordata. All of these Eriophyes species showed
      noticeable morphological differences between protogyne and deutogyne females in
      terms of the number of dorsal annuli, location of setae d, length of setae e and
      3a, distance between tubercles 3a and the length and pattern of the prodorsal
      shield. Based on a comparative morphological analysis of this original data with
      that published by A. Nalepa, new synonyms for the following species are proposed:
      Erophyes exilis (Nalepa) = Eriophyes leiosoma Nalepa syn. nov.; Eriophyes
      nervalis (Nalepa) = Eriophyes tiliaceus Nalepa syn. nov., Eriophyes tiliae Nalepa
      = Eriophyes rudis Nalepa syn. nov. = Eriophyes tomentosae Nalepa syn. nov. A key
      to all studied Eriophyes species living on lime trees is included.

PMID- 26213771
TI  - Bathydorus laniger and Docosaccus maculatus (Lyssacinosida; Hexactinellida): Two
      new species of glass sponge from the abyssal eastern North Pacific Ocean.
AB  - Two new species of glass sponge were discovered from the abyssal plain 200 km
      west of the coast of California (Station M). The sponges have similar gross
      morphology--an unusual plate-like form with basalia stilling the body above soft
      abyssal sediments. Bathydorus laniger sp. n. differs from its congeners by the
      presence of dermal and atrial stauractins; it is also supported by smooth
      hypodermal pentactins and hypoatrial hexactins. Microscleres include oxyhexasters
      and oxyhemihexasters. Docosaccus maculatus sp. n. contains large hexactins (>1
      cm), characteristic of the genus. Megascleres include dermal hexactins, atrial
      pentactins, and choanosomal hexactins and diactins. Microscleres include
      oxytipped hemihexasters and floricomes. Several features serve to differentiate
      this species from its only known congener.

PMID- 26213772
TI  - A review of the subgenus Cladoconnus Reitter of the genus Euconnus Thomson
      (Coleoptera: Staphylinidae: Scydmaeninae) from the Balkan Peninsula, Turkey and
      Caucasus.
AB  - The subgenus Cladoconnus Reitter, 1909 of the megadiverse genus Euconnus Thomson,
      1859 is redescribed and revised for the Balkan Peninsula, Turkey and Caucasus.
      The following species are described: Euconnus (Cladoconnus) gagranicus sp. nov.,
      E. (C.) ispartaensis sp. nov., E. (C.) meybohmi sp. nov., E. (C.) brachati sp.
      nov. and E. (C.) croaticus sp. nov. Lectotypes are designated for E. (C.)
      anatolicus Franz, 1997, E. (C.) dodecanicus Franz, 1966, E. (C.) robustus
      Reitter, 1882 and E. (C.) winneguthi Apfelbeck, 1907. Euconnus (Cladoconnus)
      major (Motschulsky, 1851) is placed as a junior synonym of E. (C.) motschulskii
      (Motschulsky, 1837). Two species groups, schlosseri and denticornis are defined;
      identification keys to the groups and species are given.

PMID- 26213773
TI  - A new treefrog (Hylidae: Litoria) from Kroombit Tops, east Australia, and an
      assessment of conservation status.
AB  - The Litoria phyllochroa species-group are small hylid frogs that occur in wet
      forests of south-east Australia. This group has had a long history of taxonomic
      confusion and has received little attention in the last decade. A population of
      this species-group at Kroombit Tops, several hundred kilometers north of all
      other populations, has been recognised for some time as being genetically highly
      distinct. Here we describe this population as a new species, L. kroombitensis sp.
      nov. This species is most similar to L. barringtonensis and L. pearsoniana but is
      readily distinguished based on differences in morphology, colour pattern, mating
      call and genetics. Litoria kroombitensis sp. nov. is restricted to Kroombit Tops,
      an isolated area of wet forest in south-east Queensland. The species inhabits
      slow and intermittently flowing streams in rainforest and adjoining wet
      sclerophyll forest. The tadpole of L. kroombitensis sp. nov., described herein,
      is similar in morphology and behaviour to the tadpoles of other species within
      the Litoria phyllochroa species-group, in particular L. pearsoniana. Li toria
      kroombitensis sp. nov. has a very small distribution, with all records coming
      from the headwaters of five streams, Extensive surveys since the mid-1990s have
      revealed population declines, attributable to amphibian chytrid fungus
      (Batrachochytrium dendrobatidis). Other threats include degradation of riparian
      habitat due to invasive weeds, feral pigs and livestock, and fire. Further, the
      extent of wet forest habitats at Kroombit Tops is likely to be reduced by climate
      change impacts. Litoria kroombitensis sp. nov. meets IUCN Red List criteria for
      critically endangered CR B lab (i-v) due to its small geographic range, naturally
      fragmented distribution, and observed and projected decline in populations. In
      this paper we also assess the validity of the names L. barringtonensis, L.
      pearsoniana and L. piperata. We conclude that the names L. barringtonensis and L.
      pearsoniana are valid but the validity of L. piperata requires further
      investigation.

PMID- 26213774
TI  - A synopsis of the pin-hole borers of Thailand (Coleoptera: Curculionidae:
      Platypodinae).
AB  - The present state of knowledge of the pin-hole borers of Thailand is summarised
      to provide a basis for future studies of the fauna and its economic importance in
      forestry and timber production. A checklist of the fauna is provided with
      information on local and world distribution, host trees, biology and taxonomy.
      Six faunal elements based on geographical distribution, and the host preferences
      of species are discussed. Ninety-two species have now been recorded in Thailand,
      of which forty-three are recorded here for the first time. Three species are
      endemic to Thailand. The following new combinations are given: Dinoplatypus
      piniperda (Schedl), Treptoplatypusfulgens (Schedl), both transferred from
      Platypus.

PMID- 26213775
TI  - Revision of Apocharips Fergusson (Hymenoptera: Figitidae: Charipinae) with
      description of three new species from Colombia.
AB  - The genus Apocharips is here revised. Three previously described species are
      considered as valid: Apocharips angelicae Pujade-Villar & Evenhuis, 2002, A.
      hansoni Menke, 1993, and A. trapezoidea (Hartig, 1841). Apocharips eleaphila
      (Silvestri, 1915) and A. peraperta (Silvestri, 1915) are synonymyzed with A.
      trapezoidea. Three new species are here described: Apocharips colombiana Ferrer
      Suay & Pujade-Villar n. sp., Apocharips tamanii Paretas-Martinez & Pujade-Villar
      n. sp. and Apocharips tropicale Ferrer-Suay & Paretas-Martinez n. sp. A key to
      the six species included in Apocharips is given.

PMID- 26213776
TI  - Soil insect research in South Africa. (1) A new genus of terricolous weevils with
      four new species from the Richtersveld National Park (Coleoptera: Curculionidae:
      Entiminae: Trachyphloeini).
AB  - The new genus, Nama gen. n., and four new species, N. richtersveldiana sp. n., N.
      pentamera sp. n., N. iuliae sp. n. and N. erikae sp. n., are described from the
      Richtersveld National Park. The taxonomic position of the new genus is discussed,
      and it is compared with the other Trachyphloeini native to South Africa and with
      some genera of Trachyphloeini occurring in the Palaearctic region. A key to the
      species of Nama is provided.

PMID- 26213777
TI  - The genus Boreviulisoma Brolemann, 1928--an Iberian-N African outlier of a mainly
      tropical tribe of millipedes (Diplopoda: Polydesmida: Paradoxosomatidae.
AB  - The genus Boreviulisoma Brolemann, 1928, is revised. The synonymy of Liliputia
      Attems, 1952, under Boreviulisoma is confirmed, but L. badia Attems, 1951, from
      Spain, is resurrected, as Boreviulisoma badium, from synonymy under B. liouvillei
      Brolemann, 1928 (the type species of Boreviulisoma) from Morocco. Boreviulisoma
      barrocalense n. sp. is described from the subterranean environment of the
      Algarve, the southernmost province of Portugal. The distribution of the three
      known species of Boreviulisoma is mapped, main characters of the genus and its
      species are reviewed and a key to species of the genus is included. The isolated
      occurrence of Boreviulisoma badium and B. barrocalense n. sp. in the southern
      Iberian Peninsula, together with B. liouvillei and Eviulisoma abadi Mauries,
      1985, in Morocco, as northern outposts of the chiefly Afrotropical-Neotropical
      tribe Eviulisomatini, is discussed.

PMID- 26213778
TI  - New species of the cleptoparasitic bee genus Stelis (Hymenoptera: Megachilidae,
      Anthidiini) from the Nearctic Region.
AB  - Descriptions and diagnoses of ten new Nearctic species of Stelis subgenus Stelis
      are presented: S. alta, S. anasazi, S. anthocopae, S. broemelingi, S. imperialis,
      S. joanae, S. lamelliterga, S. occidentalis, S. paiute, and S. shoshone. Six of
      these species have been reared from trapnests. Host associations, all within the
      tribe Osmiini (Megachilidae), are provided.

PMID- 26213779
TI  - Review of the Chinese species of Gynnidomorpha Turner, 1916 (Lepidoptera:
      Tortricidae: Cochylini).
AB  - Ten species of Gynnidomorpha Turner, 1916 occur in China. Gynnidomorpha
      curviphalla, sp. nov., is described, and G datetis (Diakonoff, 1984) is recorded
      from China for the first time. Images of adults and genitalia are provided, along
      with a key to all known Chinese species based on the male genitalia. A map
      showing the geographic distribution of the species is also provided.

PMID- 26213780
TI  - Revision of the genus Synelmis Chamberlin, 1919 (Annelida: Phyllodocida:
      Pilargidae) in Australia.
AB  - We provide accounts of four species of Synelmis Chamberlin, 1919 (Annelida:
      Phyllodocida: Pilargidae) from Australian and adjacent seas, including one new
      species, S. sergi sp. nov. The only previous, positively identified, record of a
      Synelmis species in the region, S. gibbsi Salazar-Vallejo, 2003, has been checked
      and the specimens re-identified here as S. knoxi Glasby, 2003, which extends the
      known range of this species to include Australia as well as New Zealand. Newly
      collected material of S. gibbsi is described from the Joseph Bonaparte Gulf, NW
      Australia. Specimens collected from NE Australia are identified here as S. rigida
      (Fauvel, 1919). Synelmis knoxi, S. gibbsi and S. rigida are all new records for
      Australia. A key to Australian species of Synelmis is provided and we tabulate
      information on the distinguishing features of all 17 species in the genus.

PMID- 26213781
TI  - A new species of the rare nematode genus Margollus Pena-Santiago, Peralta &
      Siddiqi, 1993 (Nematoda: Tylencholaimoidea) from Turkey.
AB  - Margollus turcicus sp. n., is described and illustrated from vineyard soil in
      Turkey. The new species is characterized by having a medium sized body (L=1.0-1.2
      mm); cuticle with distinct striations; radial refractive elements abundant; lip
      region distinctly narrower than the adjoining body and slightly offset from the
      body contour by a depression; cephalic and labial papillae not discernible;
      strong labial and post-labial sclerotization present; amphids well developed with
      sclerotized walls; stylet 27-28.5 microm long, odontophore distinctly flanged,
      0.3 times the odontostyle length; pharyngeal bulb offset by constriction, 33-37
      microm long; mono-opisthodelphic female genital system with anterior branch 22-41
      microm long; spicules 49 microm long; single weak ventromedian supplement and
      short hemispheroid tail in both sexes.

PMID- 26213782
TI  - Description of larvae of the Feather Blenny, Hypsoblennius hentz (Pisces:
      Blenniidae), from New York Waters.
AB  - Hypsoblennius hentz (Lesueur) larvae are described from specimens recently
      collected in the vicinity of New York Harbor and Raritan Bay. Previous
      descriptions (Hildebrand and Cable 1938) were erroneous and additionally we
      provide the first yolk-sac larval descriptions for Western Atlantic
      Hypsoblennius. H. hentz larvae are distinguished from the other Atlantic species
      by the size and distribution of preopercular spines.

PMID- 26213783
TI  - Redescription of Lystrocteisa Simon, 1884 (Araneae: Salticidae) from New
      Caledonia.
AB  - The monotypic jumping spider genus Lystrocteisa Simon, 1884 is redescribed. A new
      generic diagnosis is provided, based on both sexes, together with redescriptions
      of the male and description and illustration of the hitherto unknown female of
      the type species.

PMID- 26213784
TI  - Lamprista gen. nov. of Lecithoceridae (Lepidoptera, Gelechioidea) from New
      Guinea, with descriptions of two new species.
AB  - Lamprista gen. nov., morphologically allied to Crocanthes Meyrick, 1886, is
      described from New Guinea, based on the type species, L. emmeli sp. nov., and an
      additional species, L. ortholepida sp. nov., is described. Illustrations of the
      imagos, male and female genitalia, and wing venation of the new species are
      given. A new combination from Crocanthes is proposed: Lamprista hemipyra
      (Meyrick, 1938), comb. nov. A key to the species of Lamprista is given.

PMID- 26213786
TI  - Callyaerins from the Marine Sponge Callyspongia aerizusa: Cyclic Peptides with
      Antitubercular Activity.
AB  - Chemical investigation of the Indonesian sponge Callyspongia aerizusa afforded
      five new cyclic peptides, callyaerins I-M (1-5), along with the known callyaerins
      A-G (6-12). The structures of the new compounds were unambiguously elucidated on
      the basis of one- and two-dimensional NMR spectroscopy and mass spectrometry. In
      addition, the structures of callyaerins D (9), F (11), and G (12), previously
      available in only small amounts, have been reinvestigated and revised. All
      compounds were tested in vitro against Mycobacterium tuberculosis, as well as
      against THP-1 (human acute monocytic leukemia) and MRC-5 (human fetal lung
      fibroblast) cell lines, in order to assess their general cytotoxicity.
      Callyaerins A (6) and B (7) showed potent anti-TB activity with MIC90 values of 2
      and 5 MUM, respectively. Callyaerin C (8) was found to be less active, with an
      MIC90 value of 40 MUM. Callyaerin A (6), which showed the strongest anti-TB
      activity, was not cytotoxic to THP-1 or MRC-5 cells (IC50 > 10 MUM), which
      highlights the potential of these compounds as promising anti-TB agents.

PMID- 26213787
TI  - Electrochemiluminescence imaging for parallel single-cell analysis of active
      membrane cholesterol.
AB  - Luminol electrochemiluminescence (ECL) imaging was developed for the parallel
      measurement of active membrane cholesterol at single living cells, thus
      establishing a novel electrochemical detection technique for single cells with
      high analysis throughput and low detection limit. In our strategy, the
      luminescence generated from luminol and hydrogen peroxide upon the potential was
      recorded in one image so that hydrogen peroxide at the surface of multiple cells
      could be simultaneously analyzed. Compared with the classic microelectrode array
      for the parallel single-cell analysis, the plat electrode only was needed in our
      ECL imaging, avoiding the complexity of electrode fabrication. The optimized ECL
      imaging system showed that hydrogen peroxide as low as 10 MUM was visible and the
      efflux of hydrogen peroxide from cells could be determined. Coupled with the
      reaction between active membrane cholesterol and cholesterol oxidase to generate
      hydrogen peroxide, active membrane cholesterol at cells on the electrode was
      analyzed at single-cell level. The luminescence intensity was correlated with the
      amount of active membrane cholesterol, validating our system for single-cell
      cholesterol analysis. The relative high standard deviation on the luminescence
      suggested high cellular heterogeneities on hydrogen peroxide efflux and active
      membrane cholesterol, which exhibited the significance of single-cell analysis.
      This success in ECL imaging for single-cell analysis opens a new field in the
      parallel measurement of surface molecules at single cells. 

PMID- 26213788
TI  - Perspectives of family and veterans on family programs to support reintegration
      of returning veterans with posttraumatic stress disorder.
AB  - Combat deployment and reintegration are challenging for service members and their
      families. Although family involvement in mental health care is increasing in the
      U.S. Department of Veterans Affairs (VA) system, little is known about family
      members' preferences for services. This study elicited the perspectives of
      returning Afghanistan and Iraq war veterans with posttraumatic stress disorder
      and their families regarding family involvement in veterans' mental health care.
      Semistructured qualitative interviews were conducted with 47 veterans receiving
      care for posttraumatic stress disorder at the Central Arkansas Veterans
      Healthcare System or Oklahoma City VA Medical Center and 36 veteran-designated
      family members. Interviews addressed perceived needs related to veterans'
      readjustment to civilian life, interest in family involvement in joint
      veteran/family programs, and desired family program content. Interview data were
      analyzed using content analysis and constant comparison. Both groups strongly
      supported inclusion of family members in programs to facilitate veterans'
      postdeployment readjustment and reintegration into civilian life. Both desired
      program content focused on information, practical skills, support, and gaining
      perspective on the other's experience. Although family and veteran perspectives
      were similar, family members placed greater emphasis on parenting-related issues
      and the kinds of support they and their children needed during and after
      deployment. To our knowledge, this is the first published report on preferences
      regarding VA postdeployment reintegration support that incorporates the
      perspectives of returning male and female veterans and those of their families.
      Findings will help VA and community providers working with returning veterans
      tailor services to the needs and preferences of this important-to-engage
      population.

PMID- 26213789
TI  - Efficacy of structured approach therapy in reducing PTSD in returning veterans: A
      randomized clinical trial.
AB  - The U.S. military deployed in support to Operation Iraqi Freedom (OIF) and
      Operation Enduring Freedom (OEF) show high rates of posttraumatic stress disorder
      (PTSD) and relationship, partner, and parenting distress. Given the pervasive
      effect of combat-related PTSD on returning veterans and its effect on their loved
      ones, the investigators have developed a couples-based treatment, structured
      approach therapy (SAT), to reduce PTSD while simultaneously decreasing
      relationship and partner distress. This study presents treatment outcome data
      measuring PTSD and relationship outcomes from a randomized clinical trial (RCT)
      comparing SAT, a manualized 12-session novel couples-based PTSD treatment, to a
      manualized 12-session couples-based educational intervention (PTSD Family
      Education [PFE]). Data were collected from 57 returning veterans meeting
      Diagnostic and Statistical Manual of Mental Disorders (fourth edition, text
      revision; DSM-IV-TR) criteria for PTSD and their cohabiting partners; data
      collection was scheduled for pretreatment, posttreatment, and 3-month follow-up.
      Findings from an intent-to-treat analysis revealed that veterans receiving SAT
      showed significantly greater reductions in self-rated (PTSD Checklist; p < .0006)
      and Clinician-Administered PTSD Scale (CAPS)-rated PTSD (p < .0001) through the 3
      month follow-up compared with veterans receiving PFE; 15 of 29 (52%) veterans
      receiving SAT and 2 of 28 (7%) receiving PFE no longer met DSM-IV-TR criteria for
      PTSD. Furthermore, SAT was associated with significant improvements in veteran
      relationship adjustment, attachment avoidance, and state anxiety. Partners showed
      significant reductions in attachment anxiety. This couples-based treatment for
      combat-related PTSD appears to have a strong therapeutic effect on combat-related
      PTSD in recently returned veterans.

PMID- 26213790
TI  - Coming home: A prospective study of family reintegration following deployment to
      a war zone.
AB  - The consequences of deployment extend beyond the service member to impact the
      entire family. The current investigation evaluated the unique challenges of
      family reintegration for partnered service members using a prospective design. In
      total, 76 partnered service members who deployed on a year-long, high-risk
      mission to Iraq were assessed across the entirety of the deployment cycle, i.e.,
      pre-, during, and postdeployment. At follow-up, nearly 1 in 5 partnered service
      members reported moderate to severe difficulties in multiple aspects of family
      reintegration. Prospective interpersonal indicators such as preparations for
      deployment as a couple, shared commitment to the military, and predeployment
      relationship distress predicted postdeployment family reintegration difficulties.
      Significant interpersonal risk factors were medium to large in their effect
      sizes. Airmen's willingness to disclose deployment- and combat-related
      experiences, and postdeployment relationship distress served as concurrent
      interpersonal correlates of difficulties with family reintegration. Intrapersonal
      factors, including posttraumatic stress symptoms and alcohol misuse were
      concurrently related to challenges with family reintegration; predeployment
      alcohol misuse also predicted subsequent family reintegration difficulties.
      Additional analyses indicated that pre- and postdeployment relationship distress,
      combat disclosure, and postdeployment alcohol misuse each contributed to family
      reintegration when controlling for other intra- and interpersonal risk factors.
      Implications for prevention and early intervention strategies as well as future
      research are discussed.

PMID- 26213791
TI  - Evaluation of a psychological health and resilience intervention for military
      spouses: A pilot study.
AB  - The decade long conflicts in Iraq and Afghanistan have placed considerable strain
      on military families. Given robust data showing high rates of deployment-related
      psychological health problems in spouses and children, and the near absence of
      evidence-based psychological health programs for military families in the
      community, interventions are urgently needed to support and strengthen spouses as
      they adjust to deployment transitions and military life experiences. This Phase 1
      pilot study evaluated the feasibility and acceptability of a resiliency
      intervention for military spouses in civilian communities (HomeFront Strong;
      HFS), and generated preliminary efficacy data regarding impacts on psychological
      health and adjustment. Through two group cohorts, 14 women completed the
      intervention, with 10 women providing pre- and postgroup assessment data.
      Findings support feasibility of the intervention and high rates of program
      satisfaction. Participants reported learning new strategies and feeling more
      knowledgeable in their ability to use effective coping skills for managing
      deployment and military-related stressors. Participation in HFS was also
      associated with reduction in levels of anxiety and perceived stress, and
      improvements in life satisfaction and life engagement. HFS is a promising
      community-based intervention for military spouses designed to enhance resiliency,
      reduce negative psychological health symptoms, and improve coping.

PMID- 26213792
TI  - Help seeking by parents in military families on behalf of their young children.
AB  - Over the past decade, many children have experienced a parental deployment,
      increasing their risk for emotional and behavioral problems. Research in the
      general population has shown that while many services are available for families
      with children experiencing problems, the rate of service utilization is low. This
      study examined help-seeking processes in military families in relation to
      children's problems. We collected data on emotional and behavioral problems from
      a sample of military parents with children ranging in age from zero to 10 years.
      While prevalence of children with problems was similar to prior research, results
      in this study suggested that military parents were alert to problems. Although
      military parents' help-seeking processes were similar to those documented in
      civilian studies in many respects, we did not find a significant gender
      difference in the recognition of problems. Furthermore, we found that children's
      experiences of deployment were related to use of services. Families who used
      services most often relied on primary care providers. These findings suggest
      military families are mindful of the possibility of their children having
      problems. In addition, many families utilize civilian services. Therefore, it is
      important to ensure that front-line civilian providers fully understand the
      context of military family issues.

PMID- 26213793
TI  - Family stressors and postdeployment mental health in single versus partnered
      parents deployed in support of the wars in Afghanistan and Iraq.
AB  - Little is known about the family-related stress and postdeployment adjustment of
      single versus partnered parents deployed in support of the wars in Iraq and
      Afghanistan. This study examined exposure to family-related stressors during and
      after deployment, as well as postdeployment psychological symptoms in a national
      sample of 318 single (n = 74) and partnered (n = 244) parent veterans of
      Operation Enduring Freedom and Operation Iraqi Freedom. Results demonstrated that
      single parents experienced higher levels of concern about life and family
      disruptions during deployment, lower levels of social support during and after
      deployment, and poorer postdeployment family functioning than partnered parents.
      Single parents also reported higher posttraumatic stress symptom severity, but
      not depression or anxiety symptom severity, compared with partnered parents.
      Family-related stressors demonstrated different associations with mental health
      for single and partnered parents, suggesting that some stressor-symptom relations
      may be more salient for single parents, and others may be more salient for
      partnered parents. Findings suggest that the deployment and postdeployment
      experiences of parents differ based on their partnered status, which has
      implications for the design and provision of services to single and partnered
      parents.

PMID- 26213794
TI  - Associations of contextual risk and protective factors with fathers' parenting
      practices in the postdeployment environment.
AB  - Deployment separation and reunifications are salient contexts that directly
      impact effective family functioning and parenting for military fathers. Yet, we
      know very little about determinants of postdeployed father involvement and
      effective parenting. The present study examined hypothesized risk and protective
      factors of observed parenting for 282 postdeployed fathers who served in the
      National Guard/Reserves. Preintervention data were employed from fathers
      participating in the After Deployment, Adaptive Parenting Tools randomized
      control trial. Parenting practices were obtained from direct observation of
      father-child interaction and included measures of problem solving, harsh
      discipline, positive involvement, encouragement, and monitoring. Risk factors
      included combat exposure, negative life events, months deployed, and
      posttraumatic stress disorder symptoms. Protective factors included education,
      income, dyadic adjustment, and social support. Results of a structural equation
      model assessing risk and protective factors for an effective parenting construct
      indicated that months deployed, income, and father age were most related to
      observed parenting, explaining 16% of the variance. We are aware of no other
      study using direct parent-child observations of fathers' parenting skills
      following overseas deployment. Implications for practice and preventive
      intervention are discussed.

PMID- 26213795
TI  - MilitaryKidsConnect: Web-based prevention services for military children.
AB  - Military children often present with psychological health concerns related to
      their experience of deployments, reintegration, and frequent moves common in
      military life. MilitaryKidsConnect is a Department of Defense (DoD) Web site
      designed to enhance the coping of military children in the context of their
      military life experience. The purpose of this paper is to describe the
      development of the Web site as a resource that provides psychoeducation, coping
      strategies, and peer support to military children.

PMID- 26213785
TI  - The Regulation of Steroid Action by Sulfation and Desulfation.
AB  - Steroid sulfation and desulfation are fundamental pathways vital for a functional
      vertebrate endocrine system. After biosynthesis, hydrophobic steroids are
      sulfated to expedite circulatory transit. Target cells express transmembrane
      organic anion-transporting polypeptides that facilitate cellular uptake of
      sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate
      esters to their unconjugated, and usually active, forms. Because most steroids
      can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and
      estrone, understanding the function, tissue distribution, and regulation of
      sulfation and desulfation processes provides significant insights into normal
      endocrine function. Not surprisingly, dysregulation of these pathways is
      associated with numerous pathologies, including steroid-dependent cancers,
      polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a
      comprehensive examination of our current knowledge of endocrine-related sulfation
      and desulfation pathways. We describe the interplay between sulfatases and
      sulfotransferases, showing how their expression and regulation influences steroid
      action. Furthermore, we address the role that organic anion-transporting
      polypeptides play in regulating intracellular steroid concentrations and how
      their expression patterns influence many pathologies, especially cancer. Finally,
      the recent advances in pharmacologically targeting steroidogenic pathways will be
      examined. 

PMID- 26213796
TI  - Gender and ethnicity as moderators: Integrative data analysis of multidimensional
      family therapy randomized clinical trials.
AB  - This study examined gender and ethnicity as moderators of Multidimensional Family
      Therapy (MDFT) effectiveness for adolescent drug abuse and illustrated the
      utility of integrative data analysis (IDA; Bauer & Hussong, 2009) for assessing
      moderation. By pooling participant data from 5 independent MDFT randomized
      clinical trials (RCTs), IDA increased power to test moderation. Participants were
      646 adolescents receiving treatment for drug use, aged 11 to 17 years (M = 15.31,
      SD = 1.30), with 19% female (n = 126), 14% (n = 92) European American, 35% (n =
      225) Hispanic, and 51% (n = 329) African American. Participants were randomized
      to MDFT or active comparison treatments, which varied by study. Drug use
      involvement (i.e., frequency and consequences) was measured at study entry, 6-,
      and 12-months by a 4-indicator latent variable. Growth curve change parameters
      from multiple calibration samples were regressed on treatment effects overall and
      by moderator subgroups. MDFT reduced drug use involvement (p < .05) for all
      participant groups. Pooled comparison groups reduced drug use involvement only
      for females and Hispanics (ps < .05). MDFT was more effective than comparisons
      for males, African Americans, and European Americans (ps <.05; Cohen's d = 1.17,
      1.95, and 1.75, respectively). For females and Hispanics, there were no
      significant differences between MDFT and pooled comparison treatments, Cohen's d
      = 0.63 and 0.19, respectively. MDFT is an effective treatment for drug use among
      adolescents of both genders and varied ethnicity with males, African American,
      and European American non-Hispanic adolescents benefitting most from MDFT.

PMID- 26213797
TI  - Familial Apple Peel Jejunal Atresia with Helical Umbilical Cord Ulcerations in
      Three Consecutive Pregnancies.
AB  - Apple peel deformity is a rare form of upper intestinal atresia of unknown
      etiology. Umbilical cord ulcers can occur secondary to reflux of gastric juice
      and bile as a result of the atresia and can cause lethal intrauterine hemorrhage.
      The authors report 3 instances of congenital apple peel jejunal atresia with
      helical umbilical cord ulcers afflicting all female offspring in consecutive
      pregnancies in a single nonconsanguineous family. There was no hemorrhage from
      the cord ulcers, but all 3 pregnancies resulted in perinatal death. Although
      familial occurrence is known, our case series is probably the 1st from the Indian
      subcontinent and warrants further research into the genetic mechanisms and
      possible ethnic differences of congenital upper intestinal atresia. The causation
      of sudden fetal demise in the absence of antecedent cord hemorrhage remains
      elusive. 

PMID- 26213798
TI  - Latent Tuberculosis Infection Screening and 2-Year Outcome in Antiretroviral
      Naive HIV-Infected Patients in a Low-Prevalence Country.
AB  - BACKGROUND: Diagnosis and treatment of latent tuberculous infection decrease the
      incidence of tuberculosis (TB) in HIV-infected patients. OBJECTIVES: To evaluate
      the diagnostic yield of two IFN-gamma release assays and tuberculin skin testing
      for the screening of latent infection in HIV-infected patients. METHODS: We
      performed a prospective study in 29 referral centers for HIV care in France.
      Asymptomatic, antiretroviral-naive patients infected with HIV-1 who consented to
      participate underwent two commercial tests (T-SPOT.TB and QuantiFERON-TB Gold In
      Tube ELISA test [QFT]) and skin test at enrollment and were followed up for
      clinical events during 24 months. RESULTS: Between March 2009 and 2011, 506
      patients were included, of whom 415 performed the three tests. Median age was 38
      years (interquartile range, 31-45 yr), with median CD4 cell count of 466/MUL (337
      615 MUL), and HIV viral load of 4.5 log10 copies/ml (3.6-4.9 log10 copies/ml). At
      least one IFN-gamma release assay was positive for 55 (13.5%) patients: QFT (n =
      43), T-SPOT.TB (n = 34), both (n = 22). Skin test was positive (>5 mm) in 66
      (15.9%) patients, with intertest agreement at 81 to 86%. On multivariate
      analysis, positive IFN-gamma release assay was only correlated with country of
      birth (8.4% for France vs. 17.9% for high-prevalence countries, P = 0.004). Of
      the 55 patients with positive IFN-gamma release assay, 8 (14.5%) developed active
      TB, all within 120 days. No other case of active TB was diagnosed. Once active TB
      was excluded, IFN-gamma release assay-based latent infection prevalence was
      11.8%. CONCLUSIONS: Systematic screening for latent TB infection by IFN-gamma
      release assay identifies a population at high risk of active TB over the next
      months. An extensive diagnostic work-up for active TB must follow positive IFN
      gamma release assay, before considering treatment of latent infection. Clinical
      trial registered with www.clinicaltrials.gov (NCT00805272).

PMID- 26213800
TI  - "It's Complicated"--Sex Differences in Perceptions of Cross-Sex Friendships.
AB  - Surprisingly, little is known about how a person's sex relates to beliefs about
      cross-sex friendships. In this study, participants completed a survey in which
      they provided separate estimates for the percentage of cross-sex friendships that
      contained secret "female-on-male" and "male-on female" sexual interest, indicated
      their optimism in the idea that males and females could be "just friends," and
      reported their comfort with their partner forming a cross-sex friendship. Males
      were just as optimistic as females about the possibility and indicated similar
      levels of discomfort in response to imagining their partner entering into a cross
      sex friendship. Furthermore, males did not provide higher estimates of sexual
      interest in cross-sex friendships compared to females. Instead, a more nuanced
      pattern emerged. Males (vs. females) provided higher estimates of male-to-female
      sexual interest, but females (vs. males) provided higher estimates of female-to
      male sexual interest. 

PMID- 26213799
TI  - Why do pictures, but not visual words, reduce older adults' false memories?
AB  - Prior work shows that false memories resulting from the study of associatively
      related lists are reduced for both young and older adults when the auditory
      presentation of study list words is accompanied by related pictures relative to
      when auditory word presentation is combined with visual presentation of the word.
      In contrast, young adults, but not older adults, show a reduction in false
      memories when presented with the visual word along with the auditory word
      relative to hearing the word only. In both cases of pictures relative to visual
      words and visual words relative to auditory words alone, the benefit of picture
      and visual words in reducing false memories has been explained in terms of
      monitoring for perceptual information. In our first experiment, we provide the
      first simultaneous comparison of all 3 study presentation modalities (auditory
      only, auditory plus visual word, and auditory plus picture). Young and older
      adults show a reduction in false memories in the auditory plus picture condition,
      but only young adults show a reduction in the visual word condition relative to
      the auditory only condition. A second experiment investigates whether older
      adults fail to show a reduction in false memory in the visual word condition
      because they do not encode perceptual information in the visual word condition.
      In addition, the second experiment provides evidence that the failure of older
      adults to show the benefits of visual word presentation is related to reduced
      cognitive resources. (PsycINFO Database Record 

PMID- 26213801
TI  - Meta-Analysis of Associations Between Interleukin-10 Polymorphisms and
      Susceptibility to Vasculitis.
AB  - OBJECTIVE: This study determined whether interleukin-10 (IL-10) polymorphisms are
      associated with susceptibility to vasculitis. METHODS: A meta-analysis was
      conducted of the associations between the IL-10 -1082 G/A, -819 C/T, and -592 C/A
      polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A
      polymorphisms and vasculitis. RESULTS: A total of 21 comparative studies
      involving 4121 patients and 5504 controls were considered in the meta-analysis.
      Meta-analysis revealed no association between the IL-10-1082 G allele and
      vasculitis in all study subjects (OR = 0.927, 95% CI = 0.780-1.102, p = 0.389).
      However, disease-specific meta-analysis showed an association between Wegener's
      granulomatosis (WG) and the IL-10-1082 G allele (OR = 0.729, 95% CI = 0.547
      0.971, p = 0.031). Meta-analysis revealed an association between vasculitis and
      the IL-10-819 C allele (OR = 0.804, 95% CI = 0.706-0.916, p = 0.001) in all study
      subjects and Behcet's disease (BD) (OR = 0.724, 95% CI = 0.679-0.781, p < 1.0 *
      10(-9)). Meta-analysis of the IL-10-592 C allele showed an association with
      vasculitis in all study subjects (OR = 0.805, 95% CI = 0.619-0.938, p = 0.005)
      and BD (OR = 0.718, 95% CI = 0.661-0.781, p < 1.0 * 10(-9)). Meta-analysis of the
      IL-10 haplotype revealed an association between the GCC haplotype and vasculitis
      in Europeans (OR = 1.239, 95% CI = 1.105-1.513, p = 0.035). CONCLUSIONS: This
      meta-analysis showed that IL-10 polymorphisms are associated with vasculitis
      susceptibility, especially in WG and BD.

PMID- 26213802
TI  - An Acid-Triggered Degradable and Fluorescent Nanoscale Drug Delivery System with
      Enhanced Cytotoxicity to Cancer Cells.
AB  - To reduce side-effects of anticancer drugs, development of nanocarriers with
      precise biological functions is a critical requirement. In this study, the
      multifunctional nanoparticles combining imaging and therapy for tumor-targeted
      delivery of hydrophobic anticancer drugs were prepared via self-assembly of
      amphiphilic copolymers obtained using RAFT polymerization, specifically, acid
      labile ortho ester and galactose. First, boron-dipyrromethene dye-conjugated
      chain transfer agent provides fluorescent imaging capability for diagnostic
      application. Second, nanoparticles were stable under physiological conditions but
      degraded in acidic tumor microenvironment, leading to enhanced anticancer
      efficacy. Third, the application of biocompatible glycopolymers efficiently
      increased the target-to-background ratio through carbohydrate-protein
      interactions. Data from cell viability, cellular internalization, flow cytometry,
      biodistribution and anticancer efficacy tests showed that the drug-loaded
      nanoparticles were capable of inhibiting cancer cell proliferation with
      significantly enhanced capacity. Our newly developed multifunctional
      nanoparticles may thus facilitate the development of effective drug delivery
      systems for application in diagnosis and therapy of cancer. 

PMID- 26213803
TI  - Mitotic lifecycle of chromosomal 3xHMG-box proteins and the role of their N
      terminal domain in the association with rDNA loci and proteolysis.
AB  - The high mobility group (HMG)-box is a DNA-binding domain characteristic of
      various eukaryotic DNA-binding proteins. 3xHMG-box proteins (containing three
      copies of the HMG-box domain and a unique basic N-terminal domain) are specific
      for plants and the Arabidopsis genome encodes two versions termed 3xHMG-box1 and
      3xHMG-box2, whose expression is cell cycle-dependent, peaking during mitosis.
      Here, we analysed in detail the spatiotemporal expression, subcellular
      localisation and chromosome association of the Arabidopsis thaliana 3xHMG-box
      proteins. Live cell imaging and structured illumination microscopy revealed that
      the expression of the 3xHMG-box proteins is induced in late G2 phase of the cell
      cycle and upon nuclear envelope breakdown in prophase they rapidly associate with
      the chromosomes. 3xHMG-box1 associates preferentially with 45S rDNA loci and the
      basic N-terminal domain is involved in the targeting of rDNA loci. Shortly after
      mitosis the 3xHMG-box proteins are degraded and an N-terminal destruction-box
      mediates the proteolysis. Ectopic expression/localisation of 3xHMG-box1 in
      interphase nuclei results in reduced plant growth and various developmental
      defects including early bolting and abnormal flower morphology. The remarkable
      conservation of 3xHMG-box proteins within the plant kingdom, their characteristic
      expression during mitosis, and their striking association with chromosomes,
      suggest that they play a role in the organisation of plant mitotic chromosomes. 

PMID- 26213804
TI  - Simulation of muscle and adipose tissue deformation in the passive human pharynx.
AB  - Quantifying the contribution of passive mechanical deformation in the human
      pharynx to upper airway collapse is fundamental to understanding the competing
      biomechanical processes that maintain airway patency. This study uses finite
      element analysis to examine deformation in the passive human pharynx using an
      intricate 3D anatomical model based on computed tomography scan images. Linear
      elastic properties are assigned to bone, cartilage, ligament, tendon, and
      membrane structures based on a survey of values reported in the literature.
      Velopharyngeal and oropharyngeal cross-sectional area versus airway pressure
      slopes are determined as functions of Young's moduli of muscle and adipose
      tissue. In vivo pharyngeal mechanics for small deformations near atmospheric
      pressure are matched by altering Young's moduli of muscle and adipose tissue. The
      results indicate that Young's moduli ranging from 0.33 to 14 kPa for muscle and
      adipose tissue matched the in vivo range of area versus pressure slopes. The
      developed anatomical model and determined Young's moduli range are expected to be
      useful as a starting point for more complex simulations of human upper airway
      collapse and obstructive sleep apnea therapy.

PMID- 26213805
TI  - One-phase controlled synthesis of Au25 nanospheres and nanorods from 1.3 nm Au :
      PPh3 nanoparticles: the ligand effects.
AB  - We report the controlled synthesis of [Au25(PPh3)10(SR1)5X2](2+) nanorods (H-SR1:
      alkyl thiol, H-SC2H4Ph and H-S(n-C6H13)) and Au25(SR2)18 nanospheres (H-SR2:
      aromatic thiol, H-SPh and H-SNap) under the one-phase thiol etching reaction of
      the polydisperse Aun(PPh3)m parent-particles (core diameter: 1.3 +/- 0.4 nm, 20 <
      n < 50). These as-obtained gold nanoclusters are identified by UV-vis
      spectroscopy and matrix-assisted laser desorption ionization mass spectrometry.
      Furthermore, the conversion process, from Aun(PPh3)m nanoparticles to
      Au25(SNap)18 nanospheres, is monitored by UV-vis spectroscopy. It is observed
      that the Au25(PPh3)10(SR1)5X2 nanorods cannot convert to Au25(SR)18 nanospheres
      in the presence of excess thiol (both the alkyl and aromatic thiol) even under
      thermal conditions (e.g., 55 and 80  degrees C), indicating that both the Au25
      nanorods and nanospheres are in a stable state during the alkyl and aromatic
      thiol etching reactions, respectively. The two different conversion pathways
      (i.e., to Au25(PPh3)10(SR1)5X2 nanorods and Au25(SR2)18 nanospheres) mainly are
      attributed to the different electronic properties and the steric effects of the
      alkyl and aromatic thiol ligands. The significant ligand effect also is observed
      in catalytic CO oxidation. The Au25(SC2H4Ph)18/CeO2 catalyst shows catalytic
      activity at 80  degrees C and reaches up to 80.7% and 98.5% (based on CO
      conversion) at 100 and 150  degrees C, while Au25(SNap)18/CeO2 and
      Au25(PPh3)10(SC2H4Ph)5X2/CeO2 give rise to a low activity at 100  degrees C with
      only 3.3% and 10.2% CO conversion and 98.0% and 94.6% at 150  degrees C. 

PMID- 26213806
TI  - The Irish experience of Symphysiotomy: 40 years onwards.
AB  - The art of symphysiotomy for delivery in the instance of cephalopelvic
      disproportion has been a dying art since the advent of caesarean section but in
      Ireland this surgical procedure was not abolished until 1992. This practice is
      still present in the developing world and in some circumstances used in developed
      countries. This study offers some insights on the 40-year follow-up of patients
      who had undergone symphysiotomy. 

PMID- 26213807
TI  - gamma-Carbon Activation through N-Heterocyclic Carbene/Bronsted Acids Cooperative
      Catalysis: A Highly Enantioselective Route to delta-Lactams.
AB  - A gamma-carbon activation method that operates through N-heterocyclic
      carbene/Bronsted acid cooperative catalysis for highly enantioselective synthesis
      of delta-lactams is reported. The protocol allows the challenging remote gamma
      carbon control of regioselectivity and enantioselectivity through introduction of
      an appropriate gamma-leaving group in the enals. The reaction offers good yields
      and excellent enantioselectivities, and the resulting cyclic products can be
      easily converted into high-value drug-like derivatives. 

PMID- 26213808
TI  - Velocity asymmetry of Dzyaloshinskii domain walls in the creep and flow regimes.
AB  - We have carried out measurements of domain wall dynamics in a Pt/Co/GdOx(t) wedge
      sample with perpendicular magnetic anisotropy. When driven by an easy-axis field
      Hz in the presence of an in-plane field Hx, the domain wall propagation is
      different along [Formula: see text]x, as expected for samples presenting
      Dzyaloshinskii-Moriya (DMI) interaction. In the creep regime, the sign and the
      value of the domain wall velocity asymmetry changes along the wedge. We show that
      in our samples the domain wall speed versus Hx curves in the creep regime cannot
      be explained simply in terms of the variation of the domain wall energy with Hx,
      as suggested by previous works. For this reason the strength and the sign of the
      DMI cannot be extracted from these measurements. To obtain reliable information
      on the DMI strength using magnetic field-induced domain wall dynamics,
      measurements have been performed with high fields, bringing the DW close to the
      flow regime of propagation. In this case we find large values of the DMI,
      consistent in magnitude and sign with those obtained from Brillouin light
      scattering measurements. 

PMID- 26213809
TI  - [Complementary medicine in dermatology].

PMID- 26213810
TI  - [Obituary for Walter Burgdorf, the longtime co-editor of JDDG].

PMID- 26213811
TI  - Allergy--current insights into prevention and diagnostic workup of immediate-type
      allergy and treatment of allergic rhinoconjunctivitis.
AB  - In recent decades, the incidence of allergic diseases has dramatically increased,
      by now affecting a large percentage of the population. For a long time, allergen
      avoidance was considered the most crucial measure in primary allergy prevention.
      However, studies have increasingly shown that exposure to allergens is an
      essential prerequisite for the development of immunological tolerance. Diagnostic
      workup is based on patient history, skin tests, and measurement of specific IgE
      antibodies. The introduction of component-based diagnostic workup offer an option
      to differentiate between primary sensitization and cross-reactivity caused by
      sensitization to panallergens or sensitization to cross-reactive carbohydrate
      epitopes. Symptomatic treatment only leads to temporary relief of allergic
      symptoms. By contrast, specific immunotherapy (SIT) may have long-lasting
      therapeutic effects and potentially even result in a complete cure. The selection
      of allergens for SIT is guided by the principle of major allergens. It is
      recommended to use those preparations that have been proven safe and effective in
      controlled clinical studies. With respect to subcutaneous immunotherapy, a host
      of tested and approved extracts are available for a wide range of different
      allergens. Large clinical trials have also confirmed the efficacy of sublingual
      immunotherapy with grass and also birch pollen extracts, which has led to the
      official approval of some preparations containing these allergens. 

PMID- 26213814
TI  - Incidence trends of nonmelanoma skin cancer in Germany from 1998 to 2010.
AB  - BACKGROUND AND OBJECTIVES: Nonmelanoma skin cancer (NMSC) is the most common
      malignant neoplasm in Germany. However, little is known about incidence trends of
      NMSC and its main subtypes basal cell carcinoma (BCC) and squamous cell carcinoma
      (SCC) in Germany. MATERIAL AND METHODS: Cancer registry data from fourteen German
      federal states was used to estimate age-standardized incidence rates by
      histologic subtype. Annual percentage changes (APC) were estimated in joinpoint
      regression models, in order to assess trend shifts in the years from 1998 to
      2010. RESULTS: In Germany, incidence rates of NMSC showed a significant increase
      from 43.1 cases/100 000 in 1998 to 105.2 cases/100 000 in 2010. Incidence rates
      and incidence increases revealed large regional variations. Basal cell carcinoma
      was the most common tumor followed by SCC. Men were more frequently affected than
      women, but incidence increases were steeper in women. CONCLUSIONS: Results are
      consistent with national and international observations. The heterogeneity of
      incidence rates and their changes among federal states indicate that incidence
      changes are most likely related to improved case registration practices in German
      cancer registries.

PMID- 26213820
TI  - Cutaneous PEComa of the right lower leg.

PMID- 26213818
TI  - Waiting time and practice organization in dermatology.

PMID- 26213822
TI  - Long-term control of pleural metastasis in Stewart-Treves syndrome with single
      agent chemotherapies followed by maintenance chemotherapy.

PMID- 26213826
TI  - Therapy-resistant chronic leg ulcers.

PMID- 26213827
TI  - S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous
      pemphigoid.

PMID- 26213830
TI  - [First network meeting of the certified skin tumor centers].

PMID- 26213831
TI  - [20 years of dermatologic surgery in in Austria (AOD, OGDC) -- an inventory].

PMID- 26213832
TI  - [Obituary for Prof. Dr. med. Christiane Voit (Berlin)].

PMID- 26213834
TI  - Long-term interference at the semantic level: Evidence from blocked-cyclic
      picture matching.
AB  - Processing semantically related stimuli creates interference across various
      domains of cognition, including language and memory. In this study, we identify
      the locus and mechanism of interference when retrieving meanings associated with
      words and pictures. Subjects matched a probe stimulus (e.g., cat) to its
      associated target picture (e.g., yarn) from an array of unrelated pictures.
      Across trials, probes were either semantically related or unrelated. To test the
      locus of interference, we presented probes as either words or pictures. If
      semantic interference occurs at the stage common to both tasks, that is, access
      to semantic representations, then interference should occur in both probe
      presentation modalities. Results showed clear semantic interference effects
      independent of presentation modality and lexical frequency, confirming a semantic
      locus of interference in comprehension. To test the mechanism of interference, we
      repeated trials across 4 presentation cycles and manipulated the number of
      unrelated intervening trials (zero vs. two). We found that semantic interference
      was additive across cycles and survived 2 intervening trials, demonstrating
      interference to be long-lasting as opposed to short-lived. However, interference
      was smaller with zero versus 2 intervening trials, which we interpret to suggest
      that short-lived facilitation counteracted the long-lived interference. We
      propose that retrieving meanings associated with words/pictures from the same
      semantic category yields both interference due to long-lasting changes in
      connection strength between semantic representations (i.e., incremental learning)
      and facilitation caused by short-lived residual activation. (PsycINFO Database
      Record 

PMID- 26213835
TI  - Hitting a high note on math tests: Remembered success influences test
      preferences.
AB  - Remembered utility is the retrospective evaluation about the pleasure and pain
      associated with a past experience. It can influence choices about repeating or
      avoiding similar situations in the future (Kahneman, 2000). A set of 5
      experiments explored the remembered utility of effortful test episodes and how it
      impacted future test choices. Experiments 1-3 mimicked Kahneman, Fredrickson,
      Schreiber, and Redelmeier's (1993) cold pressor study, but used a challenging
      test experience in place of submerging one's hand in painfully cold ice water.
      Participants took a short and an extended test of difficult math problems. The
      short test was made of 30 difficult math problems. The extended test used 30
      difficult problems plus 10 moderately difficult problems. Participants made
      retrospective evaluations about the tests and chose which kind of test (short or
      extended) they wanted for their next test and for a hypothetical test 1 day
      later. Results showed that a challenging test episode extended by a more moderate
      interval was preferred to an unextended interval. Future test choices reflected
      this preference. This pattern was evidenced even when points were awarded only to
      correctly answered difficult items but not to moderately answered difficult
      items. Experiment 4 directly compared preferences for a moderate end versus a
      moderate start test, and Experiment 5 contrasted those test conditions with a
      moderate middle test condition. The findings demonstrated test-takers' bias in
      favor of test experiences that start or end on a high note. (PsycINFO Database
      Record 

PMID- 26213836
TI  - Correction to Van Moorselaar et al. (2015).
AB  - Reports an error in "Forgotten But Not Gone: Retro-Cue Costs and Benefits in a
      Double-Cueing Paradigm Suggest Multiple States in Visual Short-Term Memory" by
      Dirk van Moorselaar, Christian N. L. Olivers, Jan Theeuwes, Victor A. F. Lamme
      and Ilja G. Sligte (Journal of Experimental Psychology: Learning, Memory, and
      Cognition, Advanced Online Publication, Apr 13, 2015, np). The Figure 2 (b)
      legend printed incorrectly. The correct figure is present in the erratum. All
      versions of this article have been corrected. (The following abstract of the
      original article appeared in record 2015-15672-001.) Visual short-term memory
      (VSTM) performance is enhanced when the to-be-tested item is cued after encoding.
      This so-called retro-cue benefit is typically accompanied by a cost for the
      noncued items, suggesting that information is lost from VSTM upon presentation of
      a retrospective cue. Here we assessed whether noncued items can be restored to
      VSTM when made relevant again by a subsequent second cue. We presented either 1
      or 2 consecutive retro-cues (80% valid) during the retention interval of a change
      detection task. Relative to no cue, a valid cue increased VSTM capacity by 2
      items, while an invalid cue decreased capacity by 2. Importantly, when a second,
      valid cue followed an invalid cue, capacity regained 2 items, so that performance
      was back on par. In addition, when the second cue was also invalid, there was no
      extra loss of information from VSTM, suggesting that those items that survived a
      first invalid cue, automatically also survived a second. We conclude that these
      results are in support of a very versatile VSTM system, in which memoranda adopt
      different representational states depending on whether they are deemed relevant
      now, in the future, or not at all. We discuss a neural model that is consistent
      with this conclusion.

PMID- 26213837
TI  - "Stimulus control in intermittent and daily smokers": Correction to Shiffman,
      Dunbar, and Ferguson (2015).
AB  - In the article "Stimulus Control in Intermittent and Daily Smokers" by Saul
      Shiffman, Michael S.Dunbar, and Stuart G. Ferguson (Psychology of Addictive
      Behaviors, Advance online publication.February 23, 2015.
      http://dx.doi.org/10.1037/adb0000052), there was an error in the reported value
      in the Discussion section. The second sentence of the second paragraph should
      have read, "Notably,DS also showed strong stimulus control in this analysis,
      implying 85% accuracy in identifying smoking situations." This was a result of a
      transcription error. All versions of this article have been corrected.

PMID- 26213839
TI  - Primary Health Networks: Towards commissioning for outcomes.

PMID- 26213838
TI  - A Motion Videogame for Opioid Relapse Prevention.
AB  - OBJECTIVE: This study examined the feasibility and acceptability of a body motion
      activated videogame, targeting the prevention of opioid relapse among youth in
      the context of outpatient treatment. MATERIALS AND METHODS: Participants attended
      four weekly gameplay sessions. Surveys were conducted at baseline and following
      each week's gameplay and assessed satisfaction with gameplay, craving intensity,
      and self-efficacy to refuse opioids. RESULTS: Participants expressed a high level
      of satisfaction with the videogame throughout the 4 weeks and agreed with the
      statement that they would be more likely to attend treatment sessions if the game
      was present (mean=4.6; standard deviation [SD]=0.7) and would recommend the
      videogame to other people in treatment (mean=4.2; SD=0.8). All participants
      recommended playing the videogame as part of treatment at least weekly, with a
      third recommending playing daily. Self-reported cravings declined over the 4-week
      period from baseline (mean=12.7; SD=8.4) to Week 4 (mean=9.8; SD=8.3), although
      the decline was not significant. Although participants stated that they liked the
      game, one-third of participants had dropped out of the study by the fourth
      session of gameplay. CONCLUSIONS: Preliminary evidence indicates that a motion
      videogame for addiction recovery may be feasible and acceptable within the
      context of outpatient treatment, although additional efforts are needed to keep
      youth in treatment. Future studies are needed to assess the impact of the game on
      long-term abstinence, treatment adherence, and engagement.

PMID- 26213840
TI  - The Top End of remote and rural health need.

PMID- 26213841
TI  - Predictors of Motor Weakness and Delayed Recovery in Cervical Disk Herniation.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To identify the significant risk
      factors for motor weakness caused by cervical disk herniation and for delayed
      recovery after surgery. SUMMARY OF BACKGROUND DATA: There were a few clinical
      trials for detecting the significant risk factors for motor weakness after
      anterior cervical surgery. MATERIALS AND METHODS: We retrospectively examined 72
      patients with degenerative disk disease of the cervical spine who were treated
      with single-level anterior cervical discectomy and fusion. The possible risk
      factors, including age, sex, symptom duration, operation time, surgery level,
      preoperative radiologic parameters, and preoperative Neck Disability Index score,
      were evaluated using multivariate logistic regression analysis. RESULTS: The
      patients included 22 women and 50 men; average age, 47.1+/-7.8 years. Of these 72
      patients, 38 (52.8%) patients had motor deficit before surgery. Complete recovery
      of motor deficit was seen in 33 (86.8%) patients, and the average duration from
      surgery to complete recovery was 4.2 months. Multivariate logistic regression
      analysis showed that disk height (P=0.001, odds ratio=0.32), percentage of
      herniated nucleus pulposus (HNP) in the spinal canal (P=0.0012, odds ratio=1.24),
      and presence of signal intensity change in the spinal cord (P=0.0015, odds
      ratio=35.57) were important risk factors for motor weakness. When the cut-off
      value of disk height was 5.8 mm, the sensitivity and specificity were 39.5% and
      94.1%, respectively. When the cut-off value of HNP in the spinal canal was 28.1%,
      the sensitivity and specificity were 57.9% and 82.4%, respectively. Furthermore,
      signal intensity change was identified as an important risk factor for delayed
      recovery. CONCLUSIONS: Decreased disk height, percentage of HNP in the spinal
      canal, or presence of signal intensity change in the spinal cord seem to be the
      important risk factors for motor weakness in patients with cervical disk
      herniation. Moreover, the presence of signal intensity change in the spinal cord
      seems to be an important risk factor for delayed recovery.

PMID- 26213842
TI  - Retrospective Analysis of Thoracolumbar Junction Injuries Using the Thoracolumbar
      Injury Severity and Classification Score, American Spinal Injury Association
      Class, Injury Severity Score, Age, Sex, and Length of Hospitalization.
AB  - STUDY DESIGN: Retrospective review of patient cohort. OBJECTIVE: Our goal was to
      assess the validity of the Thoracolumbar Injury Classification and Severity
      (TLICS) score system by comparing the TLICS system to prior management of
      thoracolumbar injuries at our institution between January 1, 2006 to March 31,
      2011. SUMMARY OF BACKGROUND DATA: TLICS was introduced in 2005 to classify and
      assign treatment recommendations for injuries based on 3 axes: mechanism of
      injury, integrity of the posterior ligamentous complex, and neurological status.
      METHODS: We retrospectively obtained and analyzed patient data regarding
      thoracolumbar junction injuries at a major academic medical center servicing
      level I trauma. In addition, we compared the American Spinal Injury Association
      (ASIA) class at time of injury to last follow-up to determine if there was any
      change in neurological status after intervention. We also compared sex, injury
      severity score (ISS), length of hospitalization, and age between nonoperatively
      and operatively treated patients. RESULTS: Included in our study were 201
      patients (70% male and 30% female). We found the TLICS system agreed with prior
      thoracolumbar junction injury management at our institution 98% of the time in
      nonoperatively treated patients and 78% of the time in operatively treated
      patients. Age, sex, and ISS were not statistically significant factors in
      patients who were treated operatively versus nonoperatively, however, there was a
      trend towards higher ISS in operatively treated patients. Average TLICS score
      between nonoperative and operative groups was 1.56 and 4.8, respectively, and was
      a statistically significant difference. There was no statistically significant
      difference in ASIA class improvement between operative and nonoperative
      treatment, however, this is likely because of having only 20 patients in this
      subcohort. Of note, about 50% of the 17 operatively treated patients had
      improvement in ASIA class. CONCLUSIONS: Our data suggest that TLICS is a valuable
      tool in a spine surgeon's armamentarium in treating thoracolumbar junction
      injuries. Some surgeons might be more likely to operate on thoracolumbar junction
      injuries that should be treated nonoperatively according to the TLICS score. As
      with all classification schemes, the TLICS system should be used in conjunction
      with sound clinical judgment.

PMID- 26213843
TI  - Dexamethasone Perioperative Coanalgesia in Lumbar Spine Fusion: A Controlled
      Cohort Study of Efficacy and Safety.
AB  - PURPOSE: A 48-hour trial of dexamethasone coanalgesia became our standard
      practice in May 2008. This is our research Ethics Board-approved review of this
      experience to date with attention to perioperative narcotics use and pain scores
      for the first 48 hours after surgery as well as length of stay (LOS), wound
      healing complications, and infections in the first 6 months, compared with the
      historical precedent control cohort. METHODS: Surgical case logs identified cases
      of 1- and 2-level elective lumbar decompression and fusion surgery performed
      since protocol initiation (cases) and for a like period beforehand (controls).
      Minimum of 6 months follow-up (sufficient to identify acute and subacute wound
      healing problems and perioperative infections) information was required.
      Hospital, Pain Service, and office records were reviewed for the extraction of
      outcomes data. RESULTS: We identified 132 cases and 146 controls. In 41
      additional cases records were deficient. Baseline characteristics were
      equivalent. Cases included 70 males (53%) and 62 females (47%) of mean age 54
      years (range, 18-84 y). Seventy-five (57%) cases were narcotics dependant (mean
      of 79.5 mg-morphine-equivalent daily). Controls included 78 males (53%) and 68
      females (47%) of mean age 55 years (range, 27-85 y). Eighty-nine (61%) controls
      were narcotics dependant (mean 101.2 mg-morphine-equivalents daily). Mean
      morphine-equivalents narcotic consumption for 48 hours after surgery was 262.9 mg
      in cases and 280.7 mg in controls. VAS pain scores at 48 hours after surgery
      averaged 4.4 and 6.9 during rest and activity in the cases, and 3.7 and 6.3
      during rest and activity in the controls. LOS averaged 3.9 days in cases and 5.2
      days in controls. Delayed wound healing and surgical site infections were not
      observed in either group. CONCLUSIONS: Systemic dexamethasone after 1- and 2
      level lumbar fusion surgery demonstrated minimal impact on 48 hours perioperative
      narcotics use with no detriment to pain control, wound healing, or infections.
      LOS was shortened by 25%.

PMID- 26213844
TI  - Documentation of Ultrastructural Changes in Nucleus and Microvilli by Fish Oil in
      Experimental Colon Carcinogenesis.
AB  - Fish oil (FO) exerts a chemopreventive effect by regulating apoptosis in colon
      carcinogenesis. The present study reports the ultrastructural changes in various
      organelles on supplementation of FO in experimental colon carcinogenesis. The
      carcinogen treatment led to abnormal nuclear shape and alteration in microvilli
      number indicating cancer establishment. On the other hand, different ratios of FO
      and corn oil increased chromatin condensation along with an extensive loss of
      microvilli in a dose- and time-dependent manner which depicts an increase in
      apoptosis. The associated ultrastuctural alterations support the facilitation of
      apoptosis by FO as a mechanism for its beneficial effect in colon carcinogenesis.

PMID- 26213845
TI  - eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and
      p27Kip1 translation.
AB  - The eukaryotic translation initiation factor 3a (eIF3a) is one of the core
      subunits of the translation initiation complex eIF3, responsible for ribosomal
      subunit joining and mRNA recruitment to the ribosome. Our previous study
      identified that it was correlated with platinum response in lung cancer. The
      current study aims to test the hypothesis that eIF3a may affect the drug response
      and prognosis of ovarian cancer patients receiving platinum-based chemotherapy by
      regulating xeroderma pigmentosum complementation group C (XPC) and p27(Kip1).
      Immunohistochemistry and western blot was used to determine the expression of
      eIF3a in 126 human ovarian cancer tissues followed by association analysis of
      eIF3a expression with patient's response and survival. Ectopic over-expression
      and RNA interference knockdown of eIF3a were carried out in A2780/cisplatin (DDP)
      and its parental A2780 cells, respectively, to determine the effect of altered
      eIF3a expression on cellular response to cisplatin by employing MTT assay.
      Western Blot analyses were also carried out to determine the regulation of eIF3a
      on XPC and p27(Kip1). eIF3a expression was associated with response of ovarian
      cancer patients to DDP-based chemotherapy and their survival. Overexpression and
      knockdown of eIF3a increased and decreased the cellular response to cisplatin in
      A2780/DDP and A2780 cells, respectively. In addition, XPC and p27(Kip1) were down
      regulated by eIF3a. eIF3a improves ovarian cancer patients' response to DDP-based
      chemotherapy via down regulating XPC and p27(Kip1).

PMID- 26213846
TI  - NOP14 suppresses breast cancer progression by inhibiting NRIP1/Wnt/beta-catenin
      pathway.
AB  - NOP14, which is functionally conserved among eukaryotes, has been implicated in
      cancer development. Here, we show that NOP14 is poorly expressed in breast cancer
      cells and invasive breast cancer tissues. In vivo and in vitro studies indicated
      that NOP14 suppressed the tumorigenesis and metastasis of breast cancer cells.
      Further investigations revealed that NOP14 enhanced ERalpha expression and
      inhibited the Wnt/beta-catenin pathway by up-regulating NRIP1 expression.
      Survival analysis indicated that low NOP14 expression was significantly
      associated with poor overall survival (P = 0.0006) and disease-free survival (P =
      0.0007), suggesting that NOP14 is a potential prognostic factor in breast cancer.
      Taken together, our findings reveal that NOP14 may suppress breast cancer
      progression and provide new insights into the development of targeted therapeutic
      agents for breast cancer. 

PMID- 26213847
TI  - OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances
      the therapeutic effect of gemcitabine both in vitro and in vivo.
AB  - Despite its relative rarity, pancreatic ductal adenocarcinoma (PDAC) accounts for
      a large percentage of cancer deaths. In this study, we investigated the in vitro
      efficacy of OSI-027, a selective inhibitor of mammalian target of rapamycin
      complex 1 (mTORC1) and mTORC2, to treat PDAC cell lines alone, and in combination
      with gemcitabine (GEM). Similarly, we tested the efficacy of these two compounds
      in a xenograft mouse model of PDAC. OSI-027 significantly arrested cell cycle in
      G0/G1 phase, inhibited the proliferation of Panc-1, BxPC-3, and CFPAC-1 cells,
      and downregulated mTORC1, mTORC2, phospho-Akt, phospho-p70S6K, phospho-4E-BP1,
      cyclin D1, and cyclin-dependent kinase 4 (CDK4) in these cells. Moreover, OSI-027
      also downregulated multidrug resistance (MDR)-1, which has been implicated in
      chemotherapy resistance in PDAC cells and enhanced apoptosis induced by GEM in
      the three PDAC cell lines. When combined, OSI-027 with GEM showed synergistic
      cytotoxic effects both in vitro and in vivo. This is the first evidence of the
      efficacy of OSI-027 in PDAC and may provide the groundwork for a new clinical
      PDAC therapy. 

PMID- 26213848
TI  - Methylated arsenic metabolites bind to PML protein but do not induce cellular
      differentiation and PML-RARalpha protein degradation.
AB  - Arsenic trioxide (As2O3) is one of the most effective therapeutic agents used for
      patients with acute promyelocytic leukemia (APL). The probable explanation for
      As2O3-induced cell differentiation is the direct targeting of PML-RARalpha
      oncoprotein by As2O3, which results in initiation of PML-RARalpha degradation.
      However, after injection, As2O3 is rapidly methylated in body to different
      intermediate metabolites such as trivalent monomethylarsonous acid (MMA(III)) and
      dimethylarsinous acid (DMA(III)), therefore, it remains unknown that which
      arsenic specie is actually responsible for the therapeutic effects against APL.
      Here we have shown the role of As2O3 (as iAs(III)) and its intermediate
      metabolites (i.e., MMA(III)/DMA(III)) in NB4 cells. Inorganic iAs(III)
      predominantly showed induction of cell differentiation, while MMA(III) and
      DMA(III) specifically showed to induce mitochondria and endoplasmic reticulum
      mediated apoptosis, respectively. On the other hand, in contrast to iAs(III),
      MMA(III) showed stronger binding affinity for ring domain of PML recombinant
      protein, however, could not induce PML protein SUMOylation and
      ubiquitin/proteasome degradation. In summary, our results suggest that the
      binding of arsenicals to the ring domain of PML proteins is not associated with
      the degradation of PML-RARalpha fusion protein. Moreover, methylated arsenicals
      can efficiently lead to cellular apoptosis, however, they are incapable of
      inducing NB4 cell differentiation.

PMID- 26213849
TI  - Conditional survival estimate of acute-on-chronic hepatitis B liver failure: a
      dynamic prediction based on a multicenter cohort.
AB  - OBJECTIVES: Counseling patients with acute-on-chronic hepatitis B liver failure
      (ACHBLF) on their individual risk of short-term mortality is challenging. This
      study aimed to develop a conditional survival estimate (CSE) for predicting
      individualized mortality risk in ACHBLF patients. METHODS: We performed a large
      prospective cohort study of 278 ACHBLF patients from December 2010 to December
      2013 at three participating medical centers. The Kaplan-Meier method was used to
      calculate the cumulative overall survival (OS). Cox proportional hazard
      regression models were used to analyze the risk factors associated with OS. 4
      week CSE at "X" week after diagnostic established were calculated as CS4 =
      OS(X+4)/OS(X). RESULTS: The actual OS at 2, 4, 6, 8, 12 weeks were 80.5%, 71.8%,
      69.3%, 66.0% and 63.7%, respectively. Using CSE, the probability of surviving an
      additional 4 weeks, given that the patient had survived for 1, 3, 5, 7, 9 weeks
      was 74%, 86%, 92%, 93%, 97%, respectively. Patients with worse prognostic
      feathers, including MELD > 25, Child grade C, age > 45, HE, INR > 2.5,
      demonstrated the greatest increase in CSE over time, when compared with the
      "favorable" one (Delta36% vs. Delta10%; Delta28% vs. Delta16%; Delta29% vs.
      Delta15%; Delta60% vs. Delta12%; Delta33% vs. Delta12%; all P < 0.001;
      respectively). CONCLUSIONS: This easy-to-use CSE can accurately predict the
      changing probability of survival over time. It may facilitate risk communication
      between patients and physicians.

PMID- 26213850
TI  - Elements Provide a Clue: Nanoscale Characterization of Thin-Film Composite
      Polyamide Membranes.
AB  - In this study, we exploit the nitrogen-sulfur elemental contrast of thin-film
      composite (TFC) polyamide membranes and present, for the first time, the
      application of two elemental analysis techniques, scanning transmission electron
      microscopy-energy-dispersive X-ray spectroscopy (STEM-EDX) and X-ray
      photoelectron spectroscopy (XPS) C60+ ion-beam sputtering, to elucidate the
      nanoscale structure and chemical composition of the polyamide-polysulfone
      interface. Although STEM-EDX elemental mapping depicts the presence of a dense
      polyamide layer at the interface, it is incapable of resolving the elemental
      contrast at nanoscale resolution at the interfacial zone. Depth-resolved XPS C60+
      ion-beam sputtering enabled nanoscale characterization of the polyamide
      polysulfone interface and revealed the presence of a heterogeneous layer that
      contains both polyamide and polysulfone signatures. Our results have important
      implications for future studies to elucidate the structure-property-performance
      relationship of TFC membranes.

PMID- 26213851
TI  - Predicting the sequence specificities of DNA- and RNA-binding proteins by deep
      learning.
AB  - Knowing the sequence specificities of DNA- and RNA-binding proteins is essential
      for developing models of the regulatory processes in biological systems and for
      identifying causal disease variants. Here we show that sequence specificities can
      be ascertained from experimental data with 'deep learning' techniques, which
      offer a scalable, flexible and unified computational approach for pattern
      discovery. Using a diverse array of experimental data and evaluation metrics, we
      find that deep learning outperforms other state-of-the-art methods, even when
      training on in vitro data and testing on in vivo data. We call this approach
      DeepBind and have built a stand-alone software tool that is fully automatic and
      handles millions of sequences per experiment. Specificities determined by
      DeepBind are readily visualized as a weighted ensemble of position weight
      matrices or as a 'mutation map' that indicates how variations affect binding
      within a specific sequence. 

PMID- 26213852
TI  - Pharmacokinetic Profile and Acute Toxicological Properties of a Novel
      Radiosensitizer Cytosine-Phosphate-Guanosine Oligodeoxynucleotide 107 in Mice
      Following Intravenous and Orthotopic Administration.
AB  - The synthetic cytosine-phosphate-guanosine oligodeoxynucleotide 107 (CpG ODN107)
      is a novel radiosensitizer for glioma treatment. However, the information related
      to its pharmacokinetics and toxicity remains unclear. Therefore, the plasma
      pharmacokinetics, distribution, elimination, and acute toxicity of CpG ODN107 in
      mice were investigated in the present experiments. The results from the liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) assay showed that the plasma
      elimination half-life (t1/2beta) of CpG ODN107 in BALB/c mice varied slightly
      with the dose, and it was 0.65, 0.49, and 0.50 h at the intravenous doses of 2.5,
      5, and 10 mg/kg, respectively. CpG ODN107 rapidly and widely distributed in
      organs/tissues, except the brain and testes. The highest concentrations were
      found in the liver (28.6% of the administered dose after 0.5 h) and the kidneys
      (5.7% of the administered dose after 1 h). CpG ODN107 (0.3, 3, and 30 MUg/mL)
      could highly bind to human and mouse plasma proteins in vitro. CpG ODN107 in the
      forms of prototype was excreted in urine (1.79%) and feces (0.91%), and its
      shortened metabolites were excreted in urine (2.1%) and feces (2.2%) within the
      first 24 h. The mice in vivo optical image showed CpG ODN107 labeled with Alexa
      Fluor 680 fluorochrome (AF680) accumulated in the brain after orthotopic
      injection, eliminated very slowly, and excreted in urine compared with poly T
      labeled with AF680. The median lethal dose (LD50) of CpG ODN107 was 75.7 mg/kg
      for mice; this dose only could produce apparent spleen and liver damage, in line
      with the distribution features of CpG ODN. In conclusion, our present
      pharmacokinetic and toxicity investigation will provide helpful information to
      further pharmacodynamic and pharmacokinetic research of CpG ODN107 and other
      oligodeoxynucleotide drugs in the future.

PMID- 26213854
TI  - Anti-Proliferative and Apoptotic Effects of Methanolic Extracts from Different
      Cladonia Species on Human Breast Cancer Cells.
AB  - This study tries to elucidate the anti-proliferative and apoptotic effects of
      methanolic lichen extracts from Cladonia rangiformis and Cladonia convolute in
      MCF-7 human breast cancer cells. Lichen extracts (0-2 mg/ml) were added to MCF-7
      cells for 24 h. Cell viability was tested using 3-(4,5-dimethylthiazol- 2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay. Cell proliferation was observed using
      bromodeoxyuridine (BrdU) labelling and proliferating cell nuclear antigen (PCNA)
      by immunocytochemistry. The TUNEL method was used for cell death detection. The
      effective dose (ED50) values of methanolic extracts from C. rangiformis and C.
      convolute were found to be 0.905 and 0.977 mg/ml, respectively. Treatment with C.
      rangiformis methanolic extract (0.2-0.8 mg/ml) dose-dependently inhibited
      proliferation of MCF-7 cells as detected by BrdU incorporation. The inhibition
      was started in 0.2 mg/ml concentration of C. convoluta methanolic extract. The
      percent of PCNA immunopositive cells showed a decrease in MCF-7 cells treated
      with two lichen extracts compared to control MCF-7. Both methanolic extracts
      showed a significant increase in percentage of apoptosis-positive cells. These
      results indicate that methanolic lichen extracts from C. rangiformis and C.
      convolute inhibited proliferation of MCF-7 cells and caused apoptosis in MCF-7
      cells. The lichens may be novel natural agents for treating breast cancer
      disease. 

PMID- 26213853
TI  - Preparing Triple-Compound Heterozygous Control Material for Molecular Diagnostics
      of TPMT Allelic Variants.
AB  - The aim of the study is to present a novel approach for preparing triple-compound
      heterozygous reference material (TCH-RM) for thiopurine S-methyltransferase
      (TPMT) genotyping by using the gene synthesis technology. The polynucleotide
      chain we prepared consisted of three wild-type and three mutant segments
      corresponding to the TPMT 238G>C, 460G>A, and 719A>G polymorphic sites. TCH-RM
      characteristics were assessed via four methods: reverse hybridization, real-time
      PCR with hydrolysis probes, real-time PCR followed by subsequent melting
      temperature analysis, and DNA sequencing. Consequently, we investigated the TPMT
      genotype of 371 patients suffering from autoimmune diseases requiring
      immunosuppressive therapy with thiopurine drugs, mostly inflammatory bowel
      disease. All methods confirmed the triple heterozygous character and
      commutability of TCH-RM. In evaluating its stability we obtained very comparable
      data before and after six months of storage at -80  degrees C. The determined
      genotypes were as follows: 352 wild-type subjects (94.8%), 17 TPMT*3A
      heterozygotes (460G>A and 719A>G, 4.6%), one patient heterozygous for the TPMT*2
      allele (238G>C, 0.3%), and one TPMT*3C heterozygote (719A>G, 0.3%). The
      frequencies of TPMT*1, *3A, *3C, and *2 in the patients were 97.5%, 2.3%, 0.1%,
      and 0.1 %, respectively. Assembling segments of synthetic DNA into long
      polynucleotide chains is a universal way of obtaining compound heterozygous
      material for performing any simultaneous analysis of polymorphic sites in the
      human genome. The batches are manufactured with a perfect concentration match of
      wildtype and mutant fragments, and can be made in large quantities for most
      diagnostic techniques.

PMID- 26213855
TI  - Effect of Asenapine on the Activity of Hypocretin Neurons in Normal and
      Unpredictable Mild Stress Preconditioned Rats.
AB  - Asenapine (ASE) is a novel atypical antipsychotic used in schizophrenia
      treatment. Here, the effect of ASE on Fos expression in hypocretin (Hcrt) neurons
      in medial and lateral portions of the lateral hypothalamus (LH) and the effect of
      chronic unpredictable variable mild stress (CMS) preconditioning were studied.
      CMS consisted of restraint, social isolation, crowding, swimming, and cold and
      lasted 21 days. The rats were sacrificed on day 22, 90 min after a single
      injection of vehicle (saline 300 MUl/rat subcutaneously--s.c.) or ASE (0.3 mg/kg
      s.c.). Control (CON), ASE, CMS, and CMS+ASE groups were used. Fos protein was
      visualized by the avidin biotin peroxidase technique, while Hcrt perikarya by
      fluorescent dye. Fos/Hcrt co-localizations were evaluated under parallel light
      and fluorescent illuminations. In the single Fos expression assessment, the Fos
      number was significantly higher in the medial in comparison with the lateral LH
      portion in each group. No differences in Fos amount were observed between the
      individual groups within the medial and lateral LH portions. In the Fos/Hcrt co
      localization assessments, ASE significantly reduced the number of Fos/Hcrt
      neurons in the medial, but not lateral, LH portion in ASE and CMS+ASE groups. CMS
      only slightly contributed to the inhibitory effect of ASE in the CMS+ASE groups.
      The present data show as the first that ASE may reduce the activity of Hcrt cells
      in the medial LH portion, which might correspond with the relatively low weight
      gain liability of ASE. CMS preconditioning did not significantly interfere with
      this impact of ASE.

PMID- 26213856
TI  - Anthocyanin-Rich Diet in Chemically Induced Colitis in Mice.
AB  - The aetiology of inflammatory bowel diseases is unclear, but oxidative stress
      plays a key role in the pathogenesis. Anthocyanins--plant polyphenols--were shown
      to have antioxidant and anti-inflammatory properties. The aim of this study was
      to investigate the potential protective effects of anthocyanins on the oxidative
      status in mice with chemically induced colitis. Adult male mice were randomly
      divided into a control group drinking tap water and a colitis group drinking 1%
      dextran sulphate sodium solution. Animals had ad libitum access to a control
      wheat-based diet or food based on wheat producing anthocyanins. Bodyweight and
      stool consistency were monitored daily for 14 days. At the end of the experiment,
      colon length was measured and tissue samples were collected for the assessment of
      histology and oxidative status. Mice with colitis had lower body weight, higher
      stool score and shorter colon than control mice. Anthocyanins had neither an
      effect on stool consistency, nor on bodyweight loss and colon length. In the
      colon, liver and plasma, analysis of oxidative stress markers and antioxidant
      status revealed no significant differences between the groups. Food made from
      wheat producing anthocyanins did not protect mice from the consequences of
      chemically induced colitis. The measured biomarkers do not confirm the role of
      oxidative stress in this model of colitis. Further optimization of the
      anthocyanin-rich food might be needed before further experiments are conducted.

PMID- 26213857
TI  - The Effect of Ascorbic Acid on Mancozeb-Induced Toxicity in Rat Thymocytes.
AB  - Mancozeb, as a dithiocarbamate fungicide, has been found to exhibit toxicological
      manifestations in different cells, mainly by generation of free radicals which
      may alter antioxidant defence systems in cells. The effect of mancozeb on the
      cells of a primary lymphoid organ has not been studied. In the present study, the
      effects of mancozeb (0.2, 2 and 5 MUg/ml) or mancozeb+ascorbic acid (100 MUg/ml),
      or ascorbic acid alone or control medium alone on the levels of cell viability,
      apoptosis, intracellular reactive oxygen species production (ROS), mitochondrial
      membrane potential (MMP) and ATP levels in rat thymocytes were examined in vitro.
      Cells treated with mancozeb displayed a concentration-dependent increase of
      hypodiploid cells and ROS production followed by markedly decreased viability of
      the cells, MMP and ATP levels. Application of ascorbic acid significantly reduced
      cytotoxicity in cell cultures treated with 0.2 and 2 MUg/ml of mancozeb, together
      with significantly decreased ROS levels and increased MMP and ATP levels. In
      cells treated with 5 MUg/ml of mancozeb, ascorbic acid failed to reduce toxicity
      while simultaneously increasing the apoptosis rate of thymocytes. These results
      suggest that ROS plays a significant role in mancozeb-induced toxicity, through
      alteration of mitochondrial function. Ascorbic acid administration reduced the
      toxicity rate in cells treated with lower mancozeb concentrations, while it may
      have the ability to shift cells from necrosis to apoptosis in the presence of
      highest mancozeb concentrations. 

PMID- 26213858
TI  - miR-204 Regulates the Proliferation of Dairy Goat Spermatogonial Stem Cells via
      Targeting to Sirt1.
AB  - The regulation of spermatogonial stem cell (SSC) proliferation and self-renewal
      is a complex process. Several studies on the microRNA regulation of mammalian
      spermatogenesis have been reported. Here, we predicted miRNA targeting of Sirt1,
      and a dual luciferase experiment confirmed that miR-204 interacted with the Sirt1
      3'-untranslated region (3'-UTR). The expression of miR-204 and Sirt1 in dairy
      goat testicles was investigated, and the results showed that the expression
      pattern of Sirt1 was similar to that of miR-204 in the temporal-spatial
      distribution. The over-expression of Sirt1 in goat SSCs can promote SSCs' self
      renewal gene expression and cell proliferation. Furthermore, miRNA sequencing
      results showed that Sirt1 had a higher expression level in dairy goat CD49f(+)
      and CD90(+) SSCs, but the expression level of miR-204 was lower. In an in vitro
      assay, Sirt1 was significantly down-regulated in dairy goat SSCs when transfected
      with miR-204 mimics, indicating that Sirt1 was a target of miR-204 in the dairy
      goat. On the basis of the results of RT-qPCR, fluorescence-activated cell sorting
      (FACS), and western blotting, we found that the over-expression of Sirt1 in goat
      SSCs can promote cellular proliferation and change self-renewal and pluripotent
      gene expression. Thus, miR-204 was involved in the regulation of dairy goat SSCs
      proliferation via Sirt1. 

PMID- 26213860
TI  - Quantum State-to-State Dynamics of the H + LiH -> H2 + Li Reaction.
AB  - State-to-state quantum dynamics calculations for the H + LiH (v = 0-1, j = 0) ->
      H2 + Li reactions are performed based on an ab initio ground electronic state
      potential energy surface (PES). Total and product state-resolved integral and
      differential cross sections and rate constants are calculated. The present total
      integral cross sections and rate constants for the H + LiH (v = 0, j = 0)
      reaction are found to be in agreement with previous literature results. Product
      state-resolved integral cross sections and rate constants reveal that the H2
      products are preferred to be formed in their rovibrational excited states. The
      differential cross sections show that the intensity of forward scattering for the
      H2 products in their rovibrational excited states is stronger than other states.
      The mechanisms for the v = 0 and v = 1 reactions are found to be highly
      consistent with each other. Further, the influence of the stripping mechanism on
      the H + LiH reaction is studied. It is found that the stripping mechanism could
      be responsible for the decrease of the reactivity, the product state
      distribution, and scattering direction of the H2 products. It is related to the
      "attractive" feature of the underlying PES. 

PMID- 26213859
TI  - Forkhead Transcription Factor FOXO1 Is Regulated by Both a Stimulatory
      Thyrotropin Receptor Antibody and Insulin-Like Growth Factor-1 in Orbital
      Fibroblasts from Patients with Graves' Ophthalmopathy.
AB  - BACKGROUND: Activation of thyrotropin receptor (TSHR) and/or insulin-like growth
      factor (IGF-1) receptor (IGF-1R) enhances HA production and adipogenesis in
      orbital fibroblasts from patients with Graves' ophthalmopathy (GO) and
      recapitulates the tissue remodeling characteristic of the orbit in GO. A
      functional relationship between TSHR and IGF-1R has long been postulated, and
      recently bidirectional crosstalk between the receptors in GO fibroblasts was
      demonstrated. Because the transcription factor Forkhead box O-1 (FOXO1) was
      recently shown to be a critical downstream mediator of TSH and IGF-1 effects on
      thyrocyte proliferation, studies were designed to determine whether FOXO1 might
      similarly act as a common mediator of M22, a stimulatory TSHR antibody (TSAb),
      and IGF-1 in GO orbital fibroblasts. METHODS: FOXO1 mRNA and protein were
      measured in orbital tissue specimens derived from normal individuals and patients
      with GO. In addition, the control of FOXO1 cellular localization was investigated
      using quantitative Western blotting of fractionated cell lysates from orbital
      fibroblasts treated with M22 and/or IGF-1 with or without specific TSHR, IGF-1R,
      or PI3K/AKT1/2 inhibitors. RESULTS: Significantly lower levels of both FOXO1 mRNA
      and protein were found in GO orbital tissue specimens compared with normal
      orbital tissues (M = 39%, p = 0.043; M = 46.4%; p = 0.028, respectively). In
      addition, treatment of GO orbital cultures with M22, IGF-1, or M22 plus IGF-1
      increased cytoplasmic FOXO1 compared with control (1.63-fold, p = 0.008; 1.68
      fold, p = 0.001; 1.61-fold, p <= 0.001, respectively) and decreased nuclear FOXO1
      (M = 28%, p = 0.002; M = 38%, p <= 0.001; M = 35%, p = 0.007, respectively).
      These effects were inhibited by co-treatment with the respective, but not the
      opposite, receptor antagonist. AKT inhibition of M22 or IGF-1-treated cultures
      was found to increase nuclear (1.4-fold, p = 0.026; 1.3-fold, p = 0.001,
      respectively) and decrease cytoplasmic (24.2%, p = 0.001; 36%, p = 0.004,
      respectively) FOXO1 localization. CONCLUSIONS: These data point to FOXO1 as an
      important mediator of TSAb and IGF-1 action via their cognate receptors in GO
      orbital fibroblasts. These findings provide a link between the low FOXO1 protein
      levels demonstrated in GO orbital tissue and the tissue remodeling characteristic
      of GO, and suggest novel therapy for GO aimed at increasing nuclear expression of
      FOXO1 in GO target cells.

PMID- 26213861
TI  - Surgical technique of endometrioma excision impacts on the ovarian reserve.
      Single-port access laparoscopy versus multiport access laparoscopy: a case
      control study.
AB  - Several recent studies report the detrimental effect of endometrioma excision on
      the ovarian reserve. Surgical technique and the excessive use of bipolar
      coagulation could be the key factors. Single-port access laparoscopy (SPAL)
      ovarian cystectomy has been reported as a comparable procedure to conventional
      laparoscopy in terms of operative outcomes. The aim of this study was to evaluate
      whether the single-port surgery affects the ovarian reserve whilst performing
      laparoscopic ovarian cystectomy for unilateral endometrioma. This was a
      prospective, case-control study of 99 women with unilateral endometrioma. Forty
      nine women underwent single-port cystectomy and 50 women underwent multiport
      laparoscopic (MPL) conventional cystectomy. The primary outcome was the
      assessment of the ovarian reserve. We evaluated the serum anti-Mullerian hormone
      (AMH) levels before, 4-6 weeks and 3 months after surgery. At T2 we performed an
      ultrasound assessment of the antral follicular count (AFC). We have drawn
      attention to a statistically significant decrease of the mean AMH value and AFC
      in the SPAL group at the 4-6-week and 3-month follow-up compared to the
      conventional laparoscopy group. In conclusion, our results suggest that SPAL
      cystectomy should not be recommended to patients undergoing surgery for
      endometrioma excision who want to preserve their fertility. 

PMID- 26213862
TI  - Association of clinical androgen excess with radial artery intima media thickness
      in women with polycystic ovary syndrome.
AB  - This study explores the relationship between clinical cardiovascular risk factors
      and clinical androgen excess, with direct comparison to radial artery intima
      media thickness (rIMT). rIMT of 91 patients with polycystic ovary syndrome (PCOS)
      were compared with 72 healthy women. Patients were divided into three groups with
      regard to body mass index (BMI). Group1 = 56 women (31 controls and 25 PCOS) with
      low BMI(18-22.49 kg/m(2)), Group2 = 36 women (15 controls and 21 PCOS) with
      normal BMI (22.5-24.99 kg/m(2)) and Group3 = 71 women (26 controls and 45 PCOS)
      with high BMI (25-30 kg/m(2)). rIMT was significantly higher in patients with
      PCOS (p = 0.007). rIMT was significantly higher group1 and group3 in patients
      with PCOS compared to controls (p = 0.007 and p = 0.042, respectively). There was
      a significant positive association between rIMT levels and fT in women with PCOS
      in group1 (r = 0.24, p = 0.04). rIMT levels correlated to fT levels in women with
      PCOS in group3 (r = 0.32, p = 0.03). Modified Ferriman-Gallwey (mFG) scores
      demonstrated a positive association with free testosterone, total testosterone,
      free androgen index, waist circumference (WC), LH levels, insulin levels,
      Homeostasis Model Assessment index(HOMA-IR), rIMT and a negative correlation with
      sex hormone binding globulin in group1 and group2. mFG scores demonstrated a
      positive association with free testosterone (r = 0.33, p = 0.029) in group3, but
      no association was found between mFG and WC, HOMA-IR in group3. Our findings
      indicate that clinical androgen excess may be associated with cardiovascular
      disease in patients with PCOS. 

PMID- 26213863
TI  - Bleeding profile in users of an etonogestrel sub-dermal implant: effects of
      anthropometric variables. An observational uncontrolled preliminary study in
      Italian population.
AB  - PURPOSE: The purpose of this study is to evaluate the menstrual profile in users
      of the etonogestrel (ENG)-releasing implant (Nexplanon(r)) and the possible
      correlation with anthropometric variables. METHODS: Ninety-two healthy women,
      desiring long-term contraception with the ENG implant were enrolled in a
      prospective observational study. Anthropometric variables were measured at
      baseline and after 3, 6, 9, and 12 months. Patients recorded daily the occurrence
      of any bleeding or spotting. The bleeding/spotting pattern was evaluated over
      consecutive 90-day intervals ("Reference Periods" - RPs). Patients who showed a
      favourable bleeding profile (amenorrhoea, infrequent, or normal bleeding) for 50%
      or more of the RPs were assigned to group A, while patients with a favourable
      bleeding profile for less than 50% of the RPs were assigned to group B. RESULTS:
      Sixty-eight women (79%) were assigned to group A; 18 (21%) to group B. Group B
      had a lower baseline body mass index (BMI) than group A (24.84 +/- 4.95 kg/m(2)
      versus 20.75 +/- 4.41 kg/m(2); p < 0.005). CONCLUSIONS: The ENG sub-dermal
      implant is a well-tolerated contraceptive method, with a high proportion of women
      experiencing a favourable bleeding profile. The lower basal BMI in Group B in
      comparison with Group A may account for the higher percentage of irregular
      bleeding.

PMID- 26213864
TI  - Reframing the land-sparing/land-sharing debate for biodiversity conservation.
AB  - Conservation biologists are devoting an increasing amount of energy to debating
      whether land sparing (high-yielding agriculture on a small land footprint) or
      land sharing (low-yielding, wildlife-friendly agriculture on a larger land
      footprint) will promote better outcomes for local and global biodiversity. In
      turn, concerns are mounting about how to feed the world, given increasing demands
      for food. In this review, I evaluate the land-sparing/land-sharing framework-
      does the framework stimulate research and policy that can reconcile agricultural
      land use with biodiversity conservation, or is a revised framing needed? I review
      (1) the ecological evidence in favor of sparing versus sharing; (2) the evidence
      from land-use change studies that assesses whether a relationship exists between
      agricultural intensification and land sparing; and (3) how that relationship may
      be affected by socioeconomic and political factors. To address the trade-off
      between biodiversity conservation and food production, I then ask which forms of
      agricultural intensification can best feed the world now and in the future. On
      the basis of my review, I suggest that the dichotomy of the land-sparing/land
      sharing framework limits the realm of future possibilities to two, largely
      undesirable, options for conservation. Both large, protected regions and
      favorable surrounding matrices are needed to promote biodiversity conservation;
      they work synergistically and are not mutually exclusive. A "both-and" framing of
      large protected areas surrounded by a wildlife-friendly matrix suggests different
      research priorities from the "either-or" framing of sparing versus sharing.
      Furthermore, wildlife-friendly farming methods such as agroecology may be best
      adapted to provide food for the world's hungry people.

PMID- 26213865
TI  - Understanding the Selectivity of a Multichannel Fluorescent Probe for
      Peroxynitrite Over Hypochlorite.
AB  - Peroxynitrite is a prominent biological reactive nitrogen species from radical
      combination of nitric oxide and superoxide and fundamentally involved in broad
      spectrum physiological and pathological processes. Though redox-inert itself,
      peroxynitrite anion (OONO(-)) attacks various biological electrophiles to
      generate an array of potent 2-e(-) or 1-e(-) oxidants, which result in cell
      injuries. Development of fluorescent probes for peroxynitrite, free from
      interference from hypochlorite, has been an active endeavor of the chemical
      community. We previously reported a peroxynitrite probe (PN600), which could
      differentiate hypochlorite from peroxynitrite through a multichannel signaling
      mechanism. Herein, this intriguing selectivity was accounted for through a
      structure-reactivity relationship study. Also, this work, together with rich
      literature contributions, has allowed a qualitative guideline in the use of
      electron-rich aromatic moieties to design probes against peroxynitrite and/or
      hypochlorite. The viability of this guideline was further testified by
      development of another list of peroxynitrite selective probes. 

PMID- 26213866
TI  - Silica shelled and block copolymer encapsulated red-emissive AIE nanoparticles
      with 50% quantum yield for two-photon excited vascular imaging.
AB  - A polymer and silica co-protection strategy has been developed to encapsulate
      organic fluorogens with aggregation-induced emission and charge transfer
      characteristics into small nanoparticles (NPs). The co-pretected NPs show bright
      red fluorescence (50% quantum yield) with a large two-photon action cross-section
      (450 GM at 840 nm), which have been sucessfully used for two-photon fluorescence
      imaging of vasculature of the mouse tibial muscle. 

PMID- 26213867
TI  - What Is Value to You?

PMID- 26213870
TI  - Implementing Evidence-Based Practice to Reduce Infections Following Arthroplasty.
AB  - Surgical site infections can have a devastating effect on a patient's morbidity
      impacting their quality of life and productivity in society. Financial burdens
      are placed on healthcare organizations because of surgical site infections as
      well. Evidence has shown that it is a worthwhile endeavor to implement a practice
      to screen and treat patients who are nasal carriers of Staphylococcus aureus and
      methicillin-resistant Staphylococcus aureus. Implementing evidence-based
      practices to combat surgical site infections can help ensure quality healthcare,
      while producing best possible patient outcomes; however, getting evidence to the
      bedside can be a challenge. The Johns Hopkins nursing evidence-based practice
      model is designed to help nurses translate evidence into practice. This article
      describes the steps one community hospital took to implement an evidence-based
      practice using the Johns Hopkins model to decrease the likelihood of methicillin
      resistant Staphylococcus aureus surgical site infections in patients undergoing
      total knee arthroplasty and total hip arthroplasty. 

PMID- 26213872
TI  - The Effect of Early Ambulation on Patient Outcomes for Total Joint Replacement.
AB  - The National Association of Orthopaedic Nurses published clinical practice
      guidelines in 2010 to improve outcomes with day of surgery mobilization in the
      total joint replacement patient (). With the cost of healthcare skyrocketing and
      reimbursement marginally covering costs, healthcare professionals must look for
      ways to reduce length of stay for elective procedures. The purpose of this change
      project was to provide and measure the effectiveness of an educational
      intervention on the benefits of day of surgery mobility for nurses and physical
      therapy staff. Acquisition of caregivers' knowledge, attitudes, and practice was
      measured along with three patient outcomes (length of stay, discharge
      destination, and day of ambulation). The findings from this change project
      resulted in improvements in structure (new practice protocol), processes (nursing
      and physical therapy care processes), and patient and organization outcomes. 

PMID- 26213874
TI  - Do Elderly Patients Use Patient-Controlled Analgesia Medication Delivery Systems
      Correctly?
AB  - BACKGROUND: Although prior studies have shown patient-controlled analgesia (PCA)
      to be appropriate for use by children and adults, no studies have specifically
      evaluated the ability of elderly patients to use the technology correctly.
      PURPOSE: To determine whether elderly, postoperative patients can properly use
      PCA devices. METHODS: Using a descriptive study design, a convenience sample of
      elderly, postoperative orthopedic patients was observed while using a PCA device
      and surveyed about the proper use of the device. Participants were observed and
      surveyed 12 to 20 hours after admission to the postoperative patient care unit.
      Frequency and amount of analgesic medication administration over the
      postoperative time period were also recorded. Data were summarized with
      descriptive statistics and multiple regression analysis was used to determine
      whether confounding variables explained problems using the PCA device correctly.
      RESULTS: A total of 58 orthopedic patients were studied during the first day
      after surgery. Patients had used the PCA device for 16.6 +/- 3.0 (mean +/-SD)
      hours at the time of the observation and survey. Virtually all patients correctly
      identified and depressed the PCA activation button when instructed, knew when to
      use the PCA device, and who was allowed to depress the PCA button. Slightly more
      than half of the patients (57%) correctly identified how often they could have
      PCA medication, with 38% not sure of PCA medication frequency. The PCA medication
      was requested an average of 23.3 +/- 52.7 times during the study period. The
      majority of the patients (86%) requested PCA medication less than 25% of the
      times that they could receive PCA medication. All patients in the study had PCA
      devices programmed to deliver up to 5 doses per hour of PCA medication, yet an
      average of 11.2 +/- 10.8 doses of PCA medication were actually delivered during
      the entire study period (average 16.6 hours). Average doses of fentanyl and
      morphine sulfate received by patients were 13.5 MUg/hour and 1.0 mg/hour,
      respectively. CONCLUSION: Elderly patients were very knowledgeable about how to
      use the PCA device but not about how often they could receive PCA medication.
      This lack of knowledge may have influenced how often they requested pain
      medication, because almost 90% of patients received less than 25% of the PCA
      allowable medication dose. This low usage of PCA medication delivery calls into
      question the cost-effectiveness of this method of medication delivery for the
      elderly. Additional studies are needed to verify these findings in other elderly
      patients.

PMID- 26213876
TI  - Impact of a Focused Approach for Discharge Teaching Regarding the Use of Aspirin
      as Anticoagulant After Joint Replacement Surgery.
AB  - BACKGROUND: Patient education for the use and administration of aspirin (ASA) as
      an anticoagulant may be deficient. PURPOSE: To pilot a knowledge assessment tool
      regarding the use of aspirin (ASA) as an anticoagulant and to evaluate the impact
      of a focused approach for discharge teaching. DESIGN: One-group pretest-posttest
      pilot study. SAMPLE: Convenience sample of patients hospitalized for total knee
      and total hip arthroplasty. MEASURE: Researcher developed ASA quiz. INTERVENTION:
      Focused education on aspirin as an anticoagulant. RESULTS: There was a
      statistically significant improvement in knowledge (Wilcoxon rank sum test Z =
      3.880, p < .001).

PMID- 26213878
TI  - Cement Allergy: A Case Study.
AB  - The purpose of this article was to educate nurses about the possibility of
      patients having an allergic reaction to polymethyl methacrylate (PMMA). Although
      rare, an allergic reaction to PMMA or the bone cement used to adhere the metal
      components of a total knee arthroplasty (TKA) to the bone can cause aseptic
      loosening of a TKA ( S. A. Edwards & J. Gardiner, 2007). The prevalence of PMMA
      allergies in the population has not been reported in the literature; therefore,
      no high-level research studies on the subject are available ( K. Kaplan, C. Della
      Valle, K. Haines, & J. D. Zuckerman, 2002). A case study and literature review
      was used to construct this article. The patient, L.W., a 61-year-old, white
      woman, is a nail technician with a history of right knee pain, stiffness,
      soreness, and a decreased range of motion for one and a half years following a
      TKA. The complications from a PMMA allergy could be avoided by adding one or two
      questions to the patient's history and physical form. A complete history could
      also do away with the need for additional testing and increased medical expenses
      for the patient and the healthcare system as a whole.

PMID- 26213879
TI  - Effect of a Brief Massage on Pain, Anxiety, and Satisfaction With Pain Management
      in Postoperative Orthopaedic Patients.
AB  - BACKGROUND: The majority of massage therapy studies have evaluated 20- to 45
      minute interventions in nonsurgical patients. Studies are needed to evaluate the
      effects of a brief massage intervention that would be more clinically feasible
      for bedside clinicians to administer as an adjunct to pharmacologic pain
      management in acutely ill surgical patients. PURPOSE: To evaluate the impact of a
      brief massage intervention in conjunction with analgesic administration on pain,
      anxiety, and satisfaction with pain management in postoperative orthopaedic
      inpatients. METHODS: A convenience sample of postoperative orthopaedic patients
      was studied during two therapeutic pain treatments with an oral analgesic
      medication. A pretest, posttest, randomized, controlled trial study design, with
      crossover of subjects, was used to evaluate the effect of a 5-minute hand and arm
      massage at the time of analgesic administration. Each patient received both
      treatments (analgesic administration alone [control]; analgesic administration
      with massage) during two sequential episodes of postoperative pain. Prior to
      administration of the analgesic medication, participants rated their level of
      pain and anxiety with valid and reliable tools. Immediately after analgesic
      administration, a study investigator provided the first, randomly assigned
      treatment. Pain and anxiety were rated by the participant 5 and 45 minutes after
      medication administration. Satisfaction with pain management was also rated at
      the 45-minute time point. Study procedures were repeated for the participant's
      next requirement for analgesic medication, with the participant receiving the
      other randomly assigned treatment. Analysis of variance was used to determine
      whether pain, anxiety, and/or satisfaction with pain management differed between
      the two treatment groups and/or if treatment order was a significant factor. The
      level of significance for all tests was set at p < .05. RESULTS: Twenty-five
      postoperative patients were studied during two sequential episodes of pain, which
      required analgesic medication administration (N = 25 analgesic alone; N = 25
      analgesic with massage). Patient ages ranged from 32 to 86 years (average +/-SD =
      61.2 +/- 11.5 years). Pain and anxiety scores after medication administration
      decreased in both groups, with no significant differences found between the
      analgesic alone or analgesic with massage treatments (p > .05). Patient
      satisfaction with pain management was higher for pain treatment with massage than
      medication only (F = 6.8, df = 46, p = .012). CONCLUSION: The addition of a 5
      minute massage treatment at the time of analgesic administration significantly
      increased patient satisfaction with pain management.

PMID- 26213880
TI  - Workarounds in the Workplace: A Second Look.
AB  - Nursing workarounds have garnered increased attention over the past 15 years,
      corresponding with an increased focus on patient safety and evidence-based
      practice and a rise in the use of health information technologies (HITs).
      Workarounds have typically been viewed as deviations from best practice that put
      patients at risk for poor outcomes. However, this narrow view fails to take into
      consideration the multifactorial origins of workarounds. The authors explore the
      ways in which evidence-based protocols and HIT, designed to improve patient
      safety and quality, can have an unintended consequence of increasing the
      likelihood of nurses engaging in workarounds. The article also examines
      workarounds considering the ethical obligations of both nurses and administrative
      leaders to optimize patient safety and quality. 

PMID- 26213882
TI  - Conservative Management Following Closed Reduction of a Traumatic Anterior
      Dislocation of the Shoulder.

PMID- 26213884
TI  - Recurrent squamous cell carcinoma of the scalp treated with serial free flaps: A
      case report.
AB  - Reconstruction of large full thickness scalp defects is always a challenge. Many
      different techniques can be used, but larger defects often call for a free tissue
      transfer. The purpose of this report is to present one successful way of treating
      multiple large scalp defects. A 61-year-old man was seen with recurrent squamous
      cell carcinoma of the scalp. The lesions were of full thickness, about 10-15 cm
      in diameter and included the calvarial bone and the dura layer. The
      reconstruction process included split-thickness skin grafting, local flaps, and
      three free microvascular flaps; two latissimus dorsi flaps and one anterolateral
      thigh flap. No total flap loss was seen, but partial flap necrosis called for
      secondarily reconstruction. The final result was cosmetically acceptable and the
      patient is of good health. In conclusion, serial free microvascular flaps may be
      used with good results when dealing with large difficult and recurrent scalp
      defects.

PMID- 26213885
TI  - Targeting Adenosine Monophosphate-Activated Protein Kinase by Metformin Adjusts
      Post-Ischemic Hyperemia and Extracellular Neuronal Discharge in Transient Global
      Cerebral Ischemia.
AB  - OBJECTIVE: I/R and its subsequent reactive hyperemia results in different adverse
      effects such as brain edema and BBB disruption. AMPK activation has been
      perceived as one of the target factors for I/R treatment. We investigated the
      effect of Met (an AMPK activator) on some physiological parameters including
      vascular responses, hyperemia, BBB disruption, and electrophysiological activity
      following tGCI. METHODS: Rats were pretreated with Met for two weeks and CC was
      administered half an hour before tGCI. Brain vascular responses, hyperemia, BBB
      disruption, and electrophysiological activity were evaluated following the
      ischemia. RESULTS: Met attenuated BBB disruption and reactive hyperemia in tGCI
      rats compared with the untreated I/R rats (p < 0.001). Met administration along
      with CC in the ischemic rats reversed the beneficial effects of Met on BBB
      disruption and reactive hyperemia (p < 0.001). Electrophysiological records
      indicated that Met increased spike rates in the ischemic rats comparing with I/R
      rats (p < 0.001), whereas, CC administration blocked the beneficial effects of
      Met on the neuronal discharges (p < 0.05). CONCLUSION: We established a
      regulatory role for AMPK in vascular and electrophysiological responses to tGCI.
      Studies are ongoing to determine if activation of AMPK in the reperfusion period
      would offer similar protection.

PMID- 26213890
TI  - Predictors of HIV-related stigmas among African American and Latino religious
      congregants.
AB  - OBJECTIVES: To inform church-based stigma interventions by exploring dimensions
      of HIV stigma among African American and Latino religious congregants and
      determining how these are related to drug addiction and homosexuality stigmas and
      knowing someone HIV-positive. METHOD: In-person, self-administered surveys of
      congregants 18+ years old across 2 African American and 3 Latino churches (n =
      1,235, response rate 73%) in a western U.S. city with high HIV prevalence.
      Measures included 12 items that captured dimensions of HIV stigma, a 5-item scale
      that assessed attitudes toward people who are addicted to drugs, a 7-item scale
      assessing attitudes toward homosexuality, and questions regarding
      sociodemographics and previous communication about HIV. RESULTS: Of the survey
      participants, 63.8% were women, mean age was 40.2 years, and 34.4% were African
      American, 16.8% were U.S.-born Latinos, 16.0% were foreign-born, English-speaking
      Latinos, and 32.9% were foreign-born, Spanish-speaking Latinos. Exploratory and
      confirmatory factor analyses identified 4 dimensions of HIV stigma: discomfort
      interacting with people with HIV (4 items, alpha = .86), feelings of shame "if
      you had HIV" (3 items, alpha = .78), fears of rejection "if you had HIV" (3
      items, alpha = .71), and feelings of blame toward people with HIV (2 items, alpha
      = .65). Across all dimensions, after controlling for sociodemographic
      characteristics and previous communication about HIV, knowing someone with HIV
      was associated with lower HIV stigma, and greater stigma concerning drug
      addiction and homosexuality were associated with higher HIV stigma. CONCLUSIONS:
      Congregation-based HIV stigma reduction interventions should consider
      incorporating contact with HIV-affected people. It may also be helpful to address
      attitudes toward drug addiction and sexual orientation. (PsycINFO Database Record

PMID- 26213891
TI  - The Historical Loss Scale: Longitudinal measurement equivalence and prospective
      links to anxiety among North American indigenous adolescents.
AB  - OBJECTIVES: Thoughts of historical loss (i.e., the loss of culture, land, and
      people as a result of colonization) are conceptualized as a contributor to the
      contemporary distress experienced by North American Indigenous populations.
      Although discussions of historical loss and related constructs (e.g., historical
      trauma) are widespread within the Indigenous literature, empirical efforts to
      understand the consequence of historical loss are limited, partially because of
      the lack of valid assessments. In this study we evaluated the longitudinal
      measurement properties of the Historical Loss Scale (HLS)-a standardized measure
      that was developed to systematically examine the frequency with which Indigenous
      individuals think about historical loss-among a sample of North American
      Indigenous adolescents. We also test the hypothesis that thoughts of historical
      loss can be psychologically distressing. METHODS: Via face-to-face interviews,
      636 Indigenous adolescents from a single cultural group completed the HLS and a
      measure of anxiety at 4 time-points, which were separated by 1- to 2-year
      intervals (Mage = 12.09 years, SD = .86, 50.0% girls at baseline). RESULTS:
      Responses to the HLS were explained well by 3-factor (i.e., cultural loss, loss
      of people, and cultural mistreatment) and second-order factor structures. Both of
      these factor structures held full longitudinal metric (i.e., factor loadings) and
      scalar (i.e., intercepts) equivalence. In addition, using the second-order factor
      structure, more frequent thoughts of historical loss were associated with
      increased anxiety. CONCLUSIONS: The identified 3-factor and second-order HLS
      structures held full longitudinal measurement equivalence. Moreover, as
      predicted, our results suggest that historical loss can be psychologically
      distressing for Indigenous adolescents.

PMID- 26213892
TI  - Dual identity among immigrants: Comparing different conceptualizations, their
      measurements, and implications.
AB  - OBJECTIVES: This article aims to make a contribution to the literature by
      comparing 3 existing and often used conceptualizations and measurements of
      immigrants' dual identity: (a) high levels of identification with separate ethnic
      and national identities (Studies 1 and 2), (b) dual self-identification (Study
      1), and (c) the strength of dual identification (Study 2). METHOD: Large-scale
      survey data are used in 2 studies, capturing 6 recent immigrant groups (Afghanis,
      Chinese, Iranians, Iraqis, Polish, and Somalis; Study 1, N = 5,877) and
      immigrants from Turkey (Study 2, N = 427) to The Netherlands. We investigate the
      associations between the different measures of dual identity as well as how each
      relates to indicators of intergroup relations (perceived subgroup respect and
      perceived discrimination) and immigrants' psychological outcomes (feeling at home
      in The Netherlands, happiness, affect toward the Dutch). RESULTS: The findings
      show that dual self-identification differs most markedly from high identification
      on separate ethnic and national identities. The latter conceptualization largely
      overlaps with the strength of dual identification, both in terms of the
      classification of who is a dual identifier, as well as the associations with
      intergroup relations and immigrants' psychological outcomes. CONCLUSIONS: These
      findings help to clarify discrepant approaches to dual identity in the existing
      literature and provide guidelines for future research into dual identity among
      immigrants in Western societies. In particular, they suggest that a distinction
      between dual self-identification and measures of group identification is needed.

PMID- 26213894
TI  - Natural competence in Vibrio cholerae is controlled by a nucleoside scavenging
      response that requires CytR-dependent anti-activation.

PMID- 26213893
TI  - The catalyzed hydrogen sorption mechanism in alkali alanates.
AB  - The hydrogen sorption pathways of alkali alanates were analyzed and a mechanism
      for the catalytic hydrogen sorption was developed. Gibbs free energy values of
      selected intermediate steps were calculated based on experimentally determined
      thermodynamic data (enthalpies and entropies) of individual hydrides: MAlH4,
      M3AlH6, and MH. The values of the activation energies, based on the intermediates
      M(+), H(-), MH, and AlH3, were obtained. The mechanism of the catalytic activity
      of Ti is finally clarified: we present an atomistic model, where MAlH4 desorbs
      hydrogen through the intermediates M(+), H(-), MH, and AlH3 to the hexahydride
      M3AlH6 and finally the elemental hydride MH. The catalyst acts as a bridge to
      transfer M(+) and H(-) from MAlH4(-) to the neighboring AlH4(-), forming AlH6(3-)
      and finally isolated MH, leaving AlH3 behind, which spontaneously desorbs
      hydrogen to give Al and 1.5H2. The proposed mechanism is symmetric in the
      direction of hydrogen desorption as well as readsorption processes. 

PMID- 26213895
TI  - KdmA, a histone H3 demethylase with bipartite function, differentially regulates
      primary and secondary metabolism in Aspergillus nidulans.

PMID- 26213896
TI  - Treatment with anti-OX40L or anti-TSLP does not alter the frequency of T
      regulatory cells in allergic asthmatics.
AB  - OX40-OX40L interactions and thymic stromal lymphopoietin (TSLP) are important in
      the induction and maintenance of Th2 responses in allergic disease, whereas T
      regulatory cells (Treg) have been shown to suppress pro-inflammatory Th2
      responses. Both OX40L and TSLP have been implicated in the negative regulation of
      Treg. The effect of anti-asthma therapies on Treg is not well known. Our aim was
      to assess the effects of two monoclonal antibody therapies (anti-OX40L and anti
      TSLP) on Treg frequency using a human model of allergic asthma. We hypothesized
      that the anti-inflammatory effects of these therapies would result in an increase
      in circulating Treg (CD4(+) CD25(+) CD127(low) Foxp3(+) cells) frequency. We
      measured Treg using flow cytometry, and our results showed that neither allergen
      challenge nor monoclonal antibody therapy altered circulating Treg frequency.
      These data highlight the need for assessment of airway Treg and for a more
      complete understanding of Treg biology so as to develop pharmacologics/biologics
      that modulate Treg for asthma therapy. 

PMID- 26213897
TI  - A pH-responsive supramolecular polymer gel as an enteric elastomer for use in
      gastric devices.
AB  - Devices resident in the stomach-used for a variety of clinical applications
      including nutritional modulation for bariatrics, ingestible electronics for
      diagnosis and monitoring, and gastric-retentive dosage forms for prolonged drug
      delivery-typically incorporate elastic polymers to compress the devices during
      delivery through the oesophagus and other narrow orifices in the digestive
      system. However, in the event of accidental device fracture or migration, the non
      degradable nature of these materials risks intestinal obstruction. Here, we show
      that an elastic, pH-responsive supramolecular gel remains stable and elastic in
      the acidic environment of the stomach but can be dissolved in the neutral-pH
      environment of the small and large intestines. In a large animal model, prototype
      devices with these materials as the key component demonstrated prolonged gastric
      retention and safe passage. These enteric elastomers should increase the safety
      profile for a wide range of gastric-retentive devices. 

PMID- 26213898
TI  - Time-domain separation of optical properties from structural transitions in
      resonantly bonded materials.
AB  - The extreme electro-optical contrast between crystalline and amorphous states in
      phase-change materials is routinely exploited in optical data storage and future
      applications include universal memories, flexible displays, reconfigurable
      optical circuits, and logic devices. Optical contrast is believed to arise owing
      to a change in crystallinity. Here we show that the connection between optical
      properties and structure can be broken. Using a combination of single-shot
      femtosecond electron diffraction and optical spectroscopy, we simultaneously
      follow the lattice dynamics and dielectric function in the phase-change material
      Ge2Sb2Te5 during an irreversible state transformation. The dielectric function
      changes by 30% within 100 fs owing to a rapid depletion of electrons from
      resonantly bonded states. This occurs without perturbing the crystallinity of the
      lattice, which heats with a 2-ps time constant. The optical changes are an order
      of magnitude larger than those achievable with silicon and present new routes to
      manipulate light on an ultrafast timescale without structural changes. 

PMID- 26213899
TI  - Directing cell migration and organization via nanocrater-patterned cell-repellent
      interfaces.
AB  - Although adhesive interactions between cells and nanostructured interfaces have
      been studied extensively, there is a paucity of data on how nanostructured
      interfaces repel cells by directing cell migration and cell-colony organization.
      Here, by using multiphoton ablation lithography to pattern surfaces with
      nanoscale craters of various aspect ratios and pitches, we show that the surfaces
      altered the cells' focal-adhesion size and distribution, thus affecting cell
      morphology, migration and ultimately localization. We also show that nanocrater
      pitch can disrupt the formation of mature focal adhesions to favour the migration
      of cells towards higher-pitched regions, which present increased planar area for
      the formation of stable focal adhesions. Moreover, by designing surfaces with
      variable pitch but constant nanocrater dimensions, we were able to create
      circular and striped cellular patterns. Our surface-patterning approach, which
      does not involve chemical treatments and can be applied to various materials,
      represents a simple method to control cell behaviour on surfaces. 

PMID- 26213901
TI  - Quantification of naive and memory T-cell turnover during HIV-1 infection.
AB  - BACKGROUND: In HIV infection, the homeostasis of CD4 and CD8 T cells is
      dramatically disturbed, and several studies have pointed out that T-cell turnover
      rates are increased. To understand how the CD4 and CD8 T-cell pools are affected,
      it is important to have quantitative insights into the lifespans of the cells
      constituting the different T-lymphocyte populations. METHODS: We used long-term
      in-vivo H2O labeling and mathematical modeling to estimate the average lifespans
      of naive and memory CD4 and CD8 T cells in untreated (n = 4) and combination
      antiretroviral therapy-treated (n = 3) HIV-1-infected individuals. RESULTS:
      During untreated chronic HIV-1 infection, naive CD4 and CD8 T cells lived on
      average 618 and 271 days, whereas memory CD4 and CD8 T cells had average
      lifespans of 53 and 43 days, respectively. These lifespans were at least three
      fold shorter than those in healthy controls (n = 5). In patients on effective
      combination antiretroviral therapy with total CD4 T-cell counts in the normal
      range, we found that naive CD4 and CD8 T-cell lifespans had not completely
      normalized and were still two-fold shortened. CONCLUSION: The average lifespan of
      both naive and memory CD4 and CD8 T cells decreased during untreated chronic HIV
      1 infection. Although the turnover of the memory T-cell populations nearly
      normalized during effective treatment, the turnover of naive CD4 and CD8 T cells
      did not seem to normalize completely.

PMID- 26213902
TI  - Classification of non-Hodgkin lymphoma in South-eastern Europe: review of 632
      cases from the international non-Hodgkin lymphoma classification project.
AB  - The distribution of non-Hodgkin lymphoma (NHL) subtypes varies around the world,
      but a systematic study of South-eastern Europe (SEEU) has never been done.
      Therefore, we evaluated the relative frequencies of NHL subtypes in three SEEU
      countries--Croatia, Romania and Macedonia. Five expert haematopathologists
      reviewed 632 consecutive cases of newly diagnosed NHL from the three SEEU
      countries using the World Health Organization classification. The results were
      compared to 399 cases from North America (NA) and 580 cases from Western Europe
      (WEU). The proportions of B- and T-cell NHL and the sex distribution in SEEU were
      similar to WEU and NA. However, the median ages of patients with low- and high
      grade B-NHL in SEEU (60 and 59 years, respectively) were significantly lower than
      in NA (64 and 68 years, respectively; P < 0.05). SEEU had a significantly lower
      proportion of low-grade B-NHL (46.6%) and higher proportion of high-grade B-NHL
      (44.5%) compared to both WEU (54.5% and 36.4%, respectively) and NA (56.1% and
      34.3%, respectively). There were no significant differences in the relative
      frequencies of T-NHL subtypes. This study provides new insights into differences
      in the relative frequencies of NHL subtypes in different geographic regions.
      Epidemiological studies are needed to better characterize and explain these
      differences.

PMID- 26213900
TI  - Fluctuation-driven mechanotransduction regulates mitochondrial-network structure
      and function.
AB  - Cells can be exposed to irregular mechanical fluctuations, such as those arising
      from changes in blood pressure. Here, we report that ATP production, assessed
      through changes in mitochondrial membrane potential, is downregulated in vascular
      smooth muscle cells in culture exposed to monotonous stretch cycles when compared
      with cells exposed to a variable cyclic stretch that incorporates physiological
      levels of cycle-by-cycle variability in stretch amplitude. Variable stretch
      enhances ATP production by increasing the expression of ATP synthase's catalytic
      domain, cytochrome c oxidase and its tyrosine phosphorylation, mitofusins and PGC
      1alpha. Such a fluctuation-driven mechanotransduction mechanism is mediated by
      motor proteins and by the enhancement of microtubule-, actin- and mitochondrial
      network complexity. We also show that, in aorta rings isolated from rats,
      monotonous stretch downregulates-whereas variable stretch maintains-physiological
      vessel-wall contractility through mitochondrial ATP production. Our results have
      implications for ATP-dependent and mechanosensitive intracellular processes. 

PMID- 26213903
TI  - Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in the
      rectosigmoid: systematic review and meta-analysis.
AB  - OBJECTIVES: To review the diagnostic accuracy of transvaginal ultrasound (TVS) in
      the preoperative detection of rectosigmoid endometriosis in patients with
      clinical suspicion of deep infiltrating endometriosis (DIE), comparing enhanced
      (E-TVS) and non-enhanced approaches. METHODS: An extensive search was performed
      in MEDLINE (PubMed) and EMBASE for studies published between January 1989 and
      December 2014. The eligibility criterion was use of TVS for preoperative
      detection of rectosigmoid endometriosis in women with clinical suspicion of DIE,
      using surgical data as the reference standard. Study quality was assessed using
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines and the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2)
      tool. RESULTS: Our extended search identified a total of 801 citations, among
      which 19 studies (n = 2639) were considered eligible and included in the meta
      analysis. Overall pooled sensitivity, specificity, positive likelihood ratio
      (LR+) and negative likelihood ratio (LR-) of TVS for detecting DIE in the
      rectosigmoid were 91% (95%CI, 85-94%), 97% (95%CI, 95-98%), 33.0 (95%CI, 18.6
      58.6) and 0.10 (95%CI, 0.06-0.16), respectively. Significant heterogeneity was
      found for sensitivity (I(2) , 90.8%; Cochran Q, 195.2; P < 0.001) and specificity
      (I(2) , 76.8%; Cochran Q, 77.7; P < 0.001). We did not find statistical
      differences between non-enhanced TVS and E-TVS (P = 0.304). CONCLUSION: Overall
      diagnostic performance of TVS for DIE of the rectosigmoid is good. However,
      further studies with improved quality in design are needed. Copyright (c) 2015
      ISUOG. Published by John Wiley & Sons Ltd.

PMID- 26213904
TI  - Amorphous metal-organic frameworks for drug delivery.
AB  - We report the encapsulation of the hydrophilic model molecule calcein in the Zr
      based MOF UiO-66, followed by amorphization of the framework by ball-milling. We
      show controlled release of calcein over more than 30 days, compared with the 2
      day release period from crystalline UiO-66. 

PMID- 26213905
TI  - Predictors of the variability in neuromuscular block duration following
      succinylcholine: A prospective, observational study.
AB  - BACKGROUND: The duration of neuromuscular block (NMB) following succinylcholine
      administration is characterised by a high interindividual variability. However,
      this has not yet been quantified in a large sample of surgical patients. The
      significance of underlying clinical factors is unknown. OBJECTIVE: The objective
      of this study was to profile the variability in NMB duration following a standard
      dose of succinylcholine and to investigate contributing clinical and genetic
      factors. DESIGN: A prospective, observational study. SETTING: Tertiary referral
      centre. PATIENTS: In a total of 1630 surgical patients undergoing a rapid
      sequence induction and intubation, clinical risk factors for a prolongation in
      NMB duration following succinylcholine were assessed. In a subset of 202
      patients, additional biochemical and molecular genetic investigations of
      butyrylcholinesterase were performed. INTERVENTION: A standard 1 mg kg dose of
      succinylcholine after administration of an induction drug and an opioid. MAIN
      OUTCOME: NMB duration measured as the time between administration of
      succinylcholine until reappearance of palpable muscular response to supramaximal
      transcutaneous ulnar nerve stimulation. RESULTS: NMB varied from 80 s to 44 min
      with a median duration of 7.3 min. Sixteen percent of patients had NMB duration
      in excess of 10 min. A multivariable survival model identified physical status,
      sex, age, hepatic disease, pregnancy, history of cancer and use of etomidate or
      metoclopramide as independent risk factors for a prolonged NMB. Three novel
      butyrylcholinesterase variants were identified: p.Ile5Thr; p.Val178Ile; and
      p.Try231Ser. CONCLUSION: Neuromuscular blockade duration in excess of 10 min
      occurred in 16% of a general surgical population following a single dose of
      succinylcholine. The multivariable model of clinical risk factors for prolonged
      NMB revealed a negative predictive value of 87%, thereby indicating that absence
      of such risk factors may reliably predict a shorter duration of NMB. In patients
      with clinical risk factors for a prolonged NMB or with butyrylcholinesterase
      mutations, an alternative to succinylcholine should be considered.

PMID- 26213906
TI  - Recent Developments and Biological Activities of N-Substituted Carbazole
      Derivatives: A Review.
AB  - Carbazoles represent an important class of heterocycles. These have been reported
      to exhibit diverse biological activities such as antimicrobial, antitumor,
      antiepileptic, antihistaminic, antioxidative, anti-inflammatory, antidiarrhoeal,
      analgesic, neuroprotective and pancreatic lipase inhibition properties. A series
      of carbazole derivatives such as N-substituted carbazoles, benzocarbazoles,
      furocarbazoles, pyrrolocarbazoles, indolocarbazoles, imidazocarbazoles, etc. have
      been synthesized. The N-substituted derivatives have gained the attention of
      researchers due to their therapeutic potential against neurological disorders and
      cell proliferation. Herein an attempt is made to review the medicinal importance
      of recently synthesized N-substituted carbazoles. 

PMID- 26213907
TI  - Hepatocyte Growth Factor Mediates the Antifibrogenic Action of Ocimum bacilicum
      Essential Oil against CCl4-Induced Liver Fibrosis in Rats.
AB  - The current investigation aimed to evaluate the antifibrogenic potential of
      Ocimum basilicum essential oil (OBE) and further to explore some of its
      underlying mechanisms. Three groups of rats were used: group I (control), group
      II (CCl4 model) and group III (OBE-treated) received CCl4 and OBE 2 weeks after
      the start of CCl4 administration. Oxidative damage was assessed by the
      measurement of MDA, NO, SOD, CAT, GSH and total antioxidant capacity (TAC). Liver
      fibrosis was assessed histopathologically by Masson's trichrome staining and
      alpha-smooth muscle actin (alpha-SMA) immunostaining. Expression of hepatocyte
      growth factor (HGF) and cytochrome P450 (CYP2EI isoform) was estimated using real
      time PCR and immunohistochemistry. OBE successfully attenuated liver injury, as
      shown by histopathology, decreased serum transaminases and improved oxidative
      status of the liver. Reduced collagen deposition and alpha-SMA immuopositive
      cells indicated an abrogation of hepatic stellate cell activation by OBE.
      Furthermore, OBE was highly effective in stimulating HGF mRNA and protein
      expression and inhibiting CCl4-induced CYP2E1 down-regulation. The mechanism of
      antifibrogenic action of OBE is hypothesized to proceed via scavenging free
      radicals and activating liver regeneration by induction of HGF. These data
      suggest the use of OBE as a complementary treatment in liver fibrosis. 

PMID- 26213908
TI  - Antibacterial Activity of Protocatechuic Acid Ethyl Ester on Staphylococcus
      aureus Clinical Strains Alone and in Combination with Antistaphylococcal Drugs.
AB  - The aim of the presented study was to examine in vitro the antibacterial activity
      of protocatechuic acid ethyl ester (ethyl 3,4-dihydroxybenzoate, EDHB) against
      Staphylococcus aureus clinical isolates alone and in the combination with four
      selected antibiotics. The EDHB antimicrobial activity was tested against twenty
      S. aureus strains isolated from the clinical samples, and three reference
      strains. The phenotypes and genotypes of resistance to methicillin for the tested
      strains were defined as well as the phenotypic resistance to macrolides,
      lincosamides and streptogramin B (MLSB). EDHB displayed diverse activity against
      examined S. aureus strains with the minimal inhibitory concentration (MIC) within
      the range from 64 to 1024 ug/mL. Addition of 1/4 MIC of EDHB into the Mueller
      Hinton Agar (MHA) resulted in augmented antibacterial effect in the presence of
      clindamycin. In the case of cefoxitin no synergistic effect with EDHB was noted.
      For erythromycin and vancomycin the decrease of mean MICs in the presence of EDHB
      was observed but did not reach statistical significance. The results of the
      present study showed that in vitro EDHB possesses antibacterial activity against
      S. aureus clinical strains and triggers a synergistic antimicrobial effect with
      clindamycin and to the lesser extent with erythromycin and vancomycin. 

PMID- 26213909
TI  - A Fungal alpha-Galactosidase from Tricholoma matsutake with Broad Substrate
      Specificity and Good Hydrolytic Activity on Raffinose Family Oligosaccharides.
AB  - An acidic alpha-galactosidase designated as TMG was purified from the fruiting
      bodies The purification protocol entailed ion exchange chromatography on Q
      Sepharose and of Tricholoma matsutake with 136-fold purification and a specific
      activity of 909 units/mg. Mono-Q and fast protein liquid chromatography on
      Superdex 75. TMG is a monomeric protein exhibiting a molecular mass of 47 kDa in
      SDS-PAGE and gel filtration. The purified enzyme was identified by LC-MS/MS and
      three inner amino acid sequences were obtained. The optimum pH and temperature
      for TMG with pNPGal as substrate were pH 4.5 and 55  degrees C, respectively. The
      alpha-galactosidase activity was strongly inhibited by K+, Ca2+, Cd2+, Hg2+, Ag+
      and Zn2+ ions. The enzyme activity was inhibited by the chemical modification
      agent N-bromosuccinimide (NBS), indicating the importance of tryptophan
      residue(s) at or near the active site. Besides hydrolyzing pNPGal, TMG also
      efficaciously catalyzed the degradation of natural substrates such as stachyose,
      raffinose, and melibiose. Thus TMG can be exploited commercially for improving
      the nutritional value of soy milk by degradation of indigestible
      oligosaccharides. 

PMID- 26213910
TI  - Isolation and Identification of Cytotoxic Compounds from Aeschynomene
      fascicularis, a Mayan Medicinal Plant.
AB  - The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional
      medicine in the Yucatan peninsula. However, the compounds present in the plant
      responsible for its curative properties have not yet been investigated.
      Aeschynomene fascicularis root bark was extracted with 100% methanol to obtain a
      crude extract. The methanol extract was partitioned successively with solvents
      with increasing polarity to obtain the corresponding hexane (Hx), dichloromethane
      (DCM) and ethyl acetate fractions (EtOAc), as well as a residual water-alcoholic
      fraction. These fractions were tested for their cytotoxic activities using an MTT
      assay against Hep-2 cancer cell lines. The Hx fraction led to the isolation of
      spinochalcone C (1), spinochalcone A (2), isocordoin (3) and secundiflorol G (4).
      Their structures were identified based on spectroscopic evidence and chemical
      properties. All compounds were subjected to cytotoxicity and antiproliferative
      assays against a panel of seven cell lines, including one normal-type cell line.
      Spinochalcone A (2) exhibited cytotoxic activity against DU-145 cell line and
      antiproliferative activity against the KB cell line. Secundiflorol G (4) showed
      strong cytotoxic activity towards KB and Hep-2 cell lines. In addition,
      isocordoin (3) showed moderate activity on KB, Hep-2 and DU-145 cell lines. The
      active Compounds 2, 3 and 4 are potential therapeutic entities against cancer. 

PMID- 26213911
TI  - Photochemical and Photophysical Properties of Phthalocyanines Modified with
      Optically Active Alcohols.
AB  - Three phthalocyanine derivatives were synthesized and characterized: one modified
      with a racemic mixture of 1-(4-bromophenyl)ethanol and two other macrocycles
      modified with each one of the enantioenriched isomers (R)-1-(4
      bromophenyl)ethanol and (S)-1-(4-bromophenyl)ethanol. The compounds were
      characterized by 1H-NMR spectroscopy, mass spectrometry, UV-Vis absorption, and
      excitation and emission spectra. Additionally, partition coefficient values and
      the quantum yield of the generation of oxygen reactive species were determined.
      Interestingly, the phthalocyanine containing a (R)-1-(4-bromophenyl)ethoxy moiety
      showed higher quantum yield of reactive oxygen species generation than other
      compounds under the same conditions. In addition, the obtained fluorescence
      microscopy and cell viability results have shown that these phthalocyanines have
      different interactions with mammary MCF-7 cells. Therefore, our results indicate
      that the photochemical and biological properties of phthalocyanines with chiral
      ligands should be evaluated separately for each enantiomeric species. 

PMID- 26213912
TI  - Synthesis and Enzymatic Incorporation of Modified Deoxyuridine Triphosphates.
AB  - To expand the chemical functionality of DNAzymes and aptamers, several new
      modified deoxyuridine triphosphates have been synthesized. An important precursor
      that enables this aim is 5-aminomethyl dUTP, whereby the pendent amine serves as
      a handle for further synthetic functionalization. Five functional groups were
      conjugated to 5-aminomethyl dUTP. Incorporation assays were performed on several
      templates that demand 2-5 sequential incorporation events using several
      commercially available DNA polymerases. It was found that Vent (exo-) DNA
      polymerase efficiently incorporates all five modified dUTPs. In addition, all
      nucleoside triphosphates were capable of supporting a double-stranded exponential
      PCR amplification. Modified PCR amplicons were PCR amplified into unmodified DNA
      and sequenced to verify that genetic information was conserved through
      incorporation, amplification, and reamplification. Overall these modified dUTPs
      represent new candidate substrates for use in selections using modified
      nucleotide libraries. 

PMID- 26213913
TI  - A Near Infrared Spectroscopy (NIRS) and Chemometric Approach to Improve Apple
      Fruit Quality Management: A Case Study on the Cultivars "Cripps Pink" and
      "Braeburn".
AB  - The potential of near infrared spectroscopy (NIRS) in the wavelength range of
      1000-2500 nm for predicting quality parameters such as total soluble solids
      (TSS), acidity (TA), firmness, and individual sugars (glucose, fructose, sucrose,
      and xylose) for two cultivars of apples ("Braeburn" and "Cripps Pink") was
      studied during the pre- and post-storage periods. Simultaneously, a qualitative
      investigation on the capability of NIRS to discriminate varieties, harvest dates,
      storage periods and fruit inhomogeneity was carried out. In order to generate a
      sample set with high variability within the most relevant apple quality traits,
      three different harvest time points in combination with five different storage
      periods were chosen, and the evolution of important quality parameters was
      followed both with NIRS and wet chemical methods. By applying a principal
      component analysis (PCA) a differentiation between the two cultivars, freshly
      harvested vs. long-term stored apples and, notably, between the sun-exposed vs.
      shaded side of apples could be found. For the determination of quality parameters
      effective prediction models for titratable acid (TA) and individual sugars such
      as fructose, glucose and sucrose by using partial least square (PLS) regression
      have been developed. Our results complement earlier reports, highlighting the
      versatility of NIRS as a fast, non-invasive method for quantitative and
      qualitative studies on apples. 

PMID- 26213914
TI  - Impact of the beta-Lactam Resistance Modifier (-)-Epicatechin Gallate on the Non
      Random Distribution of Phospholipids across the Cytoplasmic Membrane of
      Staphylococcus aureus.
AB  - The polyphenol (-)-epicatechin gallate (ECg) inserts into the cytoplasmic
      membrane (CM) of methicillin-resistant Staphylococcus aureus (MRSA) and
      reversibly abrogates resistance to beta-lactam antibiotics. ECg elicits an
      increase in MRSA cell size and induces thickened cell walls. As ECg partially
      delocalizes penicillin-binding protein PBP2 from the septal division site,
      reduces PBP2 and PBP2a complexation and induces CM remodelling, we examined the
      impact of ECg membrane intercalation on phospholipid distribution across the CM
      and determined if ECg affects the equatorial, orthogonal mode of division. The
      major phospholipids of the staphylococcal CM, lysylphosphatidylglycerol (LPG),
      phosphatidylglycerol (PG), and cardiolipin (CL), were distributed in highly
      asymmetric fashion; 95%-97% of LPG was associated with the inner leaflet whereas
      PG (~90%) and CL (~80%) were found predominantly in the outer leaflet. ECg
      elicited small, significant changes in LPG distribution. Atomic force microscopy
      established that ECg-exposed cells divided in similar fashion to control
      bacteria, with a thickened band of encircling peptidoglycan representing the most
      recent plane of cell division, less distinct ribs indicative of previous sites of
      orthogonal division and concentric rings and "knobbles" representing stages of
      peptidoglycan remodelling during the cell cycle. Preservation of staphylococcal
      membrane lipid asymmetry and mode of division in sequential orthogonal planes
      appear key features of ECg-induced stress. 

PMID- 26213915
TI  - Identification of New Potential Interaction Partners for Human Cytoplasmic Copper
      Chaperone Atox1: Roles in Gene Regulation?
AB  - The human copper (Cu) chaperone Atox1 delivers Cu to P1B type ATPases in the
      Golgi network, for incorporation into essential Cu-dependent enzymes. Atox1
      homologs are found in most organisms; it is a 68-residue ferredoxin-fold protein
      that binds Cu in a conserved surface-exposed Cys-X-X-Cys (CXXC) motif. In
      addition to its well-documented cytoplasmic chaperone function, in 2008 Atox1 was
      suggested to have functionality in the nucleus. To identify new interactions
      partners of Atox1, we performed a yeast two-hybrid screen with a large human
      placenta library of cDNA fragments using Atox1 as bait. Among 98 million
      fragments investigated, 25 proteins were found to be confident interaction
      partners. Nine of these were uncharacterized proteins, and the remaining 16
      proteins were analyzed by bioinformatics with respect to cell localization,
      tissue distribution, function, sequence motifs, three-dimensional structures and
      interaction networks. Several of the hits were eukaryotic-specific proteins
      interacting with DNA or RNA implying that Atox1 may act as a modulator of gene
      regulation. Notably, because many of the identified proteins contain CXXC motifs,
      similarly to the Cu transport reactions, interactions between these and Atox1 may
      be mediated by Cu. 

PMID- 26213916
TI  - Diurnal Expression of the Per2 Gene and Protein in the Lateral Habenular Nucleus.
AB  - The suprachiasmatic nucleus plays an important role in generating circadian
      rhythms in mammals. The lateral habenular nucleus (LHb) is closely linked to this
      structure. Interestingly, the LHb shows a rhythmic firing rate in vivo and in
      vitro, and sustained oscillation of rhythmic genes in vitro. However, under the
      in vivo condition, whether rhythmic gene expression in the LHb has circadian
      rhythms remains unknown. In this study, we examined LHb tissue in rats to
      determine Period2 (Per2) gene and protein expression at six zeitgeber time points
      (ZT2, ZT6, ZT10, ZT14, ZT18, and ZT22) in a 12-h light and 12-h dark (LD)
      environment. We found that in the LD environment, Per2 gene expression and PER2
      protein levels in the LHb were higher in the day and lower in the night, showing
      periodic oscillation, with a peak at ZT10 and a trough at ZT22 (Per2 mRNA) and
      ZT18 (PER2 protein). We conclude that Per2 expression and PER2 protein levels in
      the LHb have rhythmic oscillation in vivo. This study provides a basis for
      further study on the role of the LHb in the circadian rhythm system. 

PMID- 26213917
TI  - Characterization of a Type 1 Metallothionein Gene from the Stresses-Tolerant
      Plant Ziziphus jujuba.
AB  - Plant metallothioneins (MTs) are a family of low molecular weight, cysteine-rich,
      and metal-binding proteins, which play an important role in the detoxification of
      heavy metal ions, osmotic stresses, and hormone treatment. Sequence analysis
      revealed that the open-reading frame (ORF) of ZjMT was 225 bp, which encodes a
      protein composed of 75 amino acid residues with a calculated molecular mass of
      7.376 kDa and a predicated isoelectric point (pI) of 4.83. ZjMT belongs to the
      type I MT, which consists of two highly conserved cysteine-rich terminal domains
      linked by a cysteine free region. Our studies showed that ZjMT was primarily
      localized in the cytoplasm and the nucleus of cells and ZjMT expression was up
      regulated by NaCl, CdCl2 and polyethylene glycol (PEG) treatments. Constitutive
      expression of ZjMT in wild type Arabidopsis plants enhanced their tolerance to
      NaCl stress during the germination stage. Compared with the wild type, transgenic
      plants accumulate more Cd2+ in root, but less in leaf, suggesting that ZjMT may
      have a function in Cd2+ retension in roots and, therefore, decrease the toxicity
      of Cd2+. 

PMID- 26213918
TI  - Get to Understand More from Single-Cells: Current Studies of Microfluidic-Based
      Techniques for Single-Cell Analysis.
AB  - This review describes the microfluidic techniques developed for the analysis of a
      single cell. The characteristics of microfluidic (e.g., little sample amount
      required, high-throughput performance) make this tool suitable to answer and to
      solve biological questions of interest about a single cell. This review aims to
      introduce microfluidic related techniques for the isolation, trapping and
      manipulation of a single cell. The major approaches for detection in single-cell
      analysis are introduced; the applications of single-cell analysis are then
      summarized. The review concludes with discussions of the future directions and
      opportunities of microfluidic systems applied in analysis of a single cell. 

PMID- 26213919
TI  - Effects of the Bradyrhizobium japonicum waaL (rfaL) Gene on Hydrophobicity,
      Motility, Stress Tolerance, and Symbiotic Relationship with Soybeans.
AB  - We cloned and sequenced the waaL (rfaL) gene from Bradyrhizobium japonicum, which
      infects soybean and forms nitrogen-fixing nodules on soybean roots. waaL has been
      extensively studied in the lipopolysaccharide (LPS) biosynthesis of enteric
      bacteria, but little is known about its function in (brady)rhizobial LPS
      architecture. To characterize its role as O-antigen ligase in the LPS
      biosynthesis pathway, we constructed a waaL knock-out mutant and its complemented
      strain named JS015 and CS015, respectively. LPS analysis showed that an LPS
      structure of JS015 is deficient in O-antigen as compared to that of the wild type
      and complemented strain CS015, suggesting that WaaL ligates the O-antigen to
      lipid A-core oligosaccharide to form a complete LPS. JS015 also revealed
      increased cell surface hydrophobicity, but it showed decreased motility in soft
      agar plates. In addition to the alteration in cell surface properties, disruption
      of the waaL gene caused increased sensitivity of JS015 to hydrogen peroxide,
      osmotic pressure, and novobiocin. Specifically, plant tests revealed that JS015
      failed to nodulate the host plant soybean, indicating that the rhizobial waaL
      gene is responsible for the establishment of a symbiotic relationship between
      soybean and B. japonicum. 

PMID- 26213920
TI  - Human Leukocyte Antigen Class II Alleles Are Associated with Hepatitis C Virus
      Natural Susceptibility in the Chinese Population.
AB  - Human leukocyte antigen (HLA) class II molecule influences host antigen
      presentation and anti-viral immune response. The aim of this study was to
      investigate whether single nucleotide polymorphisms (SNPs) within HLA class II
      gene were associated with different clinical outcomes of hepatitis C virus (HCV)
      infection. Three HLA class II SNPs (rs3077, rs2395309 and rs2856718) were
      genotyped by TaqMan assay among Chinese population, including 350 persistent HCV
      infection patients, 194 spontaneous viral clearance subjects and 973 HCV
      uninfected control subjects. After logistic regression analysis, the results
      indicated that the rs2856718 TC genotype was significantly associated with the
      protective effect of the HCV natural susceptibility (adjusted OR: 0.712, 95% CI:
      0.554-0.914) when compared with reference TT genotype, and this remained
      significant after false discovery rate (FDR) correction (p = 0.024). Moreover,
      the protective effect of rs2856718 was observed in dominant genetic models
      (adjusted OR: 0.726, 95% CI: 0.574-0.920), and this remained significant after
      FDR correction (p = 0.024). In stratified analysis, a significant decreased risk
      was found in rs2856718C allele in the male subgroup (adjusted OR: 0.778, 95% CI:
      0.627-0.966) and hemodialysis subgroup (adjusted OR: 0.713, 95% CI: 0.552-0.921).
      Our results indicated that the genetic variations of rs2856718 within the HLA-DQ
      gene are associated with the natural susceptibility to HCV infection among the
      Chinese population. 

PMID- 26213921
TI  - Novel Radiolytic Rotenone Derivative, Rotenoisin B with Potent Anti-Carcinogenic
      Activity in Hepatic Cancer Cells.
AB  - Rotenone, isolated from roots of derris plant, has been shown to possess various
      biological activities, which lead to attempting to develop a potent drug against
      several diseases. However, recent studies have demonstrated that rotenone has the
      potential to induce several adverse effects such as a neurodegenerative disease.
      Radiolytic transformation of the rotenone with gamma-irradiation created a new
      product, named rotenoisin B. The present work was designed to investigate the
      anticancer activity of rotenoisin B with low toxicity and its molecular mechanism
      in hepatic cancer cells compared to a parent compound, rotenone. Our results
      showed rotenoisin B inhibited hepatic cancer cells' proliferation in a dose
      dependent manner and increased in apoptotic cells. Interestingly, rotenoisin B
      showed low toxic effects on normal cells compared to rotenone. Mitochondrial
      transmembrane potential has been decreased, which leads to cytochrome c release.
      Down regulation of anti-apoptotic Bcl-2 levels as well as the up regulation of
      proapoptotic Bax levels were observed. The cleaved PARP (poly ADP-ribose
      polymerase) level increased as well. Moreover, phosphorylation of extracellular
      signal regulated kinase (ERK) and p38 slightly up regulated and intracellular
      reactive oxygen species (ROS) increased as well as cell cycle arrest
      predominantly at the G2/M phase observed. These results suggest that rotenoisin B
      might be a potent anticancer candidate similar to rotenone in hepatic cancer
      cells with low toxicity to normal cells even at high concentrations compared to
      rotenone. 

PMID- 26213922
TI  - Differential DNA Methylation in Relation to Age and Health Risks of Obesity.
AB  - The aim of this study was to evaluate whether genome-wide levels of DNA
      methylation are associated with age and the health risks of obesity (HRO);
      defined according to BMI categories as "Low HRO" (overweight and class 1 obesity)
      versus "High HRO" (class 2 and class 3 obesity). Anthropometric measurements were
      assessed in a subsample of 48 volunteers from the Metabolic Syndrome Reduction in
      Navarra (RESMENA) study and 24 women from another independent study, Effects of
      Lipoic Acid and Eicosapentaenoic Acid in Human Obesity (OBEPALIP study). In the
      pooled population; the methylation levels of 55 CpG sites were significantly
      associated with age after Benjamini-Hochberg correction. In addition, DNA
      methylation of three CpG sites located in ELOVL2; HOXC4 and PI4KB were further
      negatively associated with their mRNA levels. Although no differentially
      methylated CpG sites were identified in relation to HRO after multiple testing
      correction; several nominally significant CpG sites were identified in genes
      related to insulin signaling; energy and lipid metabolism. Moreover,
      statistically significant associations between BMI or mRNA levels and two HRO
      related CpG sites located in GPR133 and ITGB5 are reported. As a conclusion,
      these findings from two Spanish cohorts add knowledge about the important role of
      DNA methylation in the age-related regulation of gene expression. In addition; a
      relevant influence of age on DNA methylation in white blood cells was found, as
      well as, on a trend level, novel associations between DNA methylation and
      obesity. 

PMID- 26213923
TI  - The miR-200 Family: Versatile Players in Epithelial Ovarian Cancer.
AB  - The role of microRNAs (miRNAs or miRs) in the pathology of epithelial ovarian
      cancer (EOC) has been extensively studied. Many miRNAs differentially expressed
      in EOC as compared to normal controls have been identified, prompting further
      inquiry into their role in the disease. miRNAs belonging to the miR-200 family
      have repeatedly surfaced over multiple profiling studies. In this review, we
      attempt to consolidate the data from different studies and highlight mechanisms
      by which these miRNAs influence progression of metastasis and chemo-resistance in
      EOC. 

PMID- 26213925
TI  - Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to
      Compensatory K2P3.1- and KV1.3-Dependent Mechanisms.
AB  - Lymphocytes express potassium channels that regulate physiological cell
      functions, such as activation, proliferation and migration. Expression levels of
      K2P5.1 (TASK2; KCNK5) channels belonging to the family of two-pore domain
      potassium channels have previously been correlated to the activity of
      autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid
      arthritis. In humans, K2P5.1 channels are upregulated upon T cell stimulation and
      influence T cell effector functions. However, a further clinical translation of
      targeting K2P5.1 is currently hampered by a lack of highly selective inhibitors,
      making it necessary to evaluate the impact of KCNK5 in established preclinical
      animal disease models. We here demonstrate that K2P5.1 knockout (K2P5.1-/-) mice
      display no significant alterations concerning T cell cytokine production,
      proliferation rates, surface marker molecules or signaling pathways. In an
      experimental model of autoimmune neuroinflammation, K2P5.1-/- mice show a
      comparable disease course to wild-type animals and no major changes in the
      peripheral immune system or CNS compartment. A compensatory upregulation of the
      potassium channels K2P3.1 and KV1.3 seems to counterbalance the deletion of
      K2P5.1. As an alternative model mimicking autoimmune neuroinflammation,
      experimental autoimmune encephalomyelitis in the common marmoset has been
      proposed, especially for testing the efficacy of new potential drugs. Initial
      experiments show that K2P5.1 is functionally expressed on marmoset T lymphocytes,
      opening up the possibility for assessing future K2P5.1-targeting drugs. 

PMID- 26213924
TI  - Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open
      Questions.
AB  - Spinal cord injury (SCI) is a major health problem and is associated with a
      diversity of neurological symptoms. Pathophysiologically, dysfunction after SCI
      results from the culmination of tissue damage produced both by the primary insult
      and a range of secondary injury mechanisms. The application of hypothermia has
      been demonstrated to be neuroprotective after SCI in both experimental and human
      studies. The myriad of protective mechanisms of hypothermia include the slowing
      down of metabolism, decreasing free radical generation, inhibiting excitotoxicity
      and apoptosis, ameliorating inflammation, preserving the blood spinal cord
      barrier, inhibiting astrogliosis, promoting angiogenesis, as well as decreasing
      axonal damage and encouraging neurogenesis. Hypothermia has also been combined
      with other interventions, such as antioxidants, anesthetics, alkalinization and
      cell transplantation for additional benefit. Although a large body of work has
      reported on the effectiveness of hypothermia as a neuroprotective approach after
      SCI and its application has been translated to the clinic, a number of questions
      still remain regarding its use, including the identification of hypothermia's
      therapeutic window, optimal duration and the most appropriate rewarming rate. In
      addition, it is necessary to investigate the neuroprotective effect of combining
      therapeutic hypothermia with other treatment strategies for putative synergies,
      particularly those involving neurorepair. 

PMID- 26213926
TI  - Technologies for Single-Cell Isolation.
AB  - The handling of single cells is of great importance in applications such as cell
      line development or single-cell analysis, e.g., for cancer research or for
      emerging diagnostic methods. This review provides an overview of technologies
      that are currently used or in development to isolate single cells for subsequent
      single-cell analysis. Data from a dedicated online market survey conducted to
      identify the most relevant technologies, presented here for the first time, shows
      that FACS (fluorescence activated cell sorting) respectively Flow cytometry (33%
      usage), laser microdissection (17%), manual cell picking (17%), random
      seeding/dilution (15%), and microfluidics/lab-on-a-chip devices (12%) are
      currently the most frequently used technologies. These most prominent
      technologies are described in detail and key performance factors are discussed.
      The survey data indicates a further increasing interest in single-cell isolation
      tools for the coming years. Additionally, a worldwide patent search was performed
      to screen for emerging technologies that might become relevant in the future. In
      total 179 patents were found, out of which 25 were evaluated by screening the
      title and abstract to be relevant to the field. 

PMID- 26213929
TI  - An Autonomous Satellite Time Synchronization System Using Remotely Disciplined VC
      OCXOs.
AB  - An autonomous remote clock control system is proposed to provide time
      synchronization and frequency syntonization for satellite to satellite or ground
      to satellite time transfer, with the system comprising on-board voltage
      controlled oven controlled crystal oscillators (VC-OCXOs) that are disciplined to
      a remote master atomic clock or oscillator. The synchronization loop aims to
      provide autonomous operation over extended periods, be widely applicable to a
      variety of scenarios and robust. A new architecture comprising the use of
      frequency division duplex (FDD), synchronous time division (STDD) duplex and code
      division multiple access (CDMA) with a centralized topology is employed. This new
      design utilizes dual one-way ranging methods to precisely measure the clock
      error, adopts least square (LS) methods to predict the clock error and employs a
      third-order phase lock loop (PLL) to generate the voltage control signal. A
      general functional model for this system is proposed and the error sources and
      delays that affect the time synchronization are discussed. Related algorithms for
      estimating and correcting these errors are also proposed. The performance of the
      proposed system is simulated and guidance for selecting the clock is provided. 

PMID- 26213928
TI  - Analysis of Android Device-Based Solutions for Fall Detection.
AB  - Falls are a major cause of health and psychological problems as well as
      hospitalization costs among older adults. Thus, the investigation on automatic
      Fall Detection Systems (FDSs) has received special attention from the research
      community during the last decade. In this area, the widespread popularity,
      decreasing price, computing capabilities, built-in sensors and multiplicity of
      wireless interfaces of Android-based devices (especially smartphones) have
      fostered the adoption of this technology to deploy wearable and inexpensive
      architectures for fall detection. This paper presents a critical and thorough
      analysis of those existing fall detection systems that are based on Android
      devices. The review systematically classifies and compares the proposals of the
      literature taking into account different criteria such as the system
      architecture, the employed sensors, the detection algorithm or the response in
      case of a fall alarms. The study emphasizes the analysis of the evaluation
      methods that are employed to assess the effectiveness of the detection process.
      The review reveals the complete lack of a reference framework to validate and
      compare the proposals. In addition, the study also shows that most research works
      do not evaluate the actual applicability of the Android devices (with limited
      battery and computing resources) to fall detection solutions. 

PMID- 26213930
TI  - Selective Surface Acoustic Wave-Based Organophosphorus Sensor Employing a Host
      Guest Self-Assembly Monolayer of beta-Cyclodextrin Derivative.
AB  - Self-assembly and molecular imprinting technologies are very attractive
      technologies for the development of artificial recognition systems and provide
      chemical recognition based on need and not happenstance. In this paper, we
      employed a b-cyclodextrin derivative surface acoustic wave (SAW) chemical sensor
      for detecting the chemical warfare agents (CWAs) sarin (O-Isoprophyl
      methylphosphonofluoridate, GB). Using sarin acid (isoprophyl hydrogen
      methylphosphonate) as an imprinting template, mono[6-deoxy-6
      [(mercaptodecamethylene)thio]]-beta-cyclodextrin was prepared by self-assembled
      method on one of the SAW oscillators. After templates' removal, a sensitive and
      selective molecular imprinting (MIP) monolayer for GB was prepared.
      Electrochemical impedance spectroscopy and atomic force microscope (AFM) were
      used to characterize this film. Comparing the detection results to GB by MIP film
      and non-MIP film, the molecularly imprinting effect was also proved. The
      resulting SAW sensor could detect sarin as low as 0.10 mg/m3 at room temperature
      and the frequency shift was about 300 Hz. The response frequency increased
      linearly with increasing sarin concentration in the range of 0.7 mg/m3~3.0 mg/m3.
      When sarin was detected under different temperatures, the SAW sensor exhibited
      outstanding sensitivity and reliability. 

PMID- 26213931
TI  - Development of a Plug-and-Play Monitoring System for Cabled Observatories in the
      East China Sea.
AB  - Seafloor observatories enable long term, continuous and multidisciplinary
      observations, promising major breakthroughs in marine environment research. The
      effort to remotely control in situ multidisciplinary equipment performing
      individual and cooperative tasks is both a challenge and a guarantee for the
      stable operations of functional observatories. With China starting to establish
      ocean observatory sensor networks, in this study we describe a monitoring system
      for cabled observatories in the East China Sea (ESOMS) that enables this effort
      in a plug and play way. An information oriented monitoring architecture for ESOMS
      was first introduced, derived from a layered control model for ocean observatory
      sensor network. The architecture contained three components and enabled
      bidirectional information flow of observation data and commands, based on which
      architecture components were designed to enable plug-and-play control within
      related model layers. A control method enabled by general junction box (GJB) and
      ocean sensor markup language (OSML) was thus proposed as the plug-and-play
      solution for implementing ESOMS. The GJB-OSML enabled control method (GOE Control
      Method) mainly actualized two processes, one of which was that the in situ GJB
      interfaced and represented every attached sensor as a Sensing Endpoint in the
      cabled observatory network. The other process was that the remote ESOMS utilized
      the same IP/Port related information modeled by OSML to create/operate a Function
      Node acted as agent of the in situ sensor. A case study for using ESOMS in the
      Xiaoqushan Seafloor Observatory was finally presented to prove its performance
      and applicability. Given this successful engineering trial, the ESOMS design and
      implementation could be applicable and beneficial for similar efforts in future
      construction of seafloor observatory network both at home and abroad. 

PMID- 26213927
TI  - Autonomic Dysregulation in Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is a chronic, progressive central neurological disease
      characterized by inflammation and demyelination. In patients with MS,
      dysregulation of the autonomic nervous system may present with various clinical
      symptoms including sweating abnormalities, urinary dysfunction, orthostatic
      dysregulation, gastrointestinal symptoms, and sexual dysfunction. These autonomic
      disturbances reduce the quality of life of affected patients and constitute a
      clinical challenge to the physician due to variability of clinical presentation
      and inconsistent data on diagnosis and treatment. Early diagnosis and initiation
      of individualized interdisciplinary and multimodal strategies is beneficial in
      the management of autonomic dysfunction in MS. This review summarizes the current
      literature on the most prevalent aspects of autonomic dysfunction in MS and
      provides reference to underlying pathophysiological mechanisms as well as means
      of diagnosis and treatment. 

PMID- 26213932
TI  - Fusion of Visible and Thermal Descriptors Using Genetic Algorithms for Face
      Recognition Systems.
AB  - The aim of this article is to present a new face recognition system based on the
      fusion of visible and thermal features obtained from the most current local
      matching descriptors by maximizing face recognition rates through the use of
      genetic algorithms. The article considers a comparison of the performance of the
      proposed fusion methodology against five current face recognition methods and
      classic fusion techniques used commonly in the literature. These were selected by
      considering their performance in face recognition. The five local matching
      methods and the proposed fusion methodology are evaluated using the standard
      visible/thermal database, the Equinox database, along with a new database, the
      PUCV-VTF, designed for visible-thermal studies in face recognition and described
      for the first time in this work. The latter is created considering visible and
      thermal image sensors with different real-world conditions, such as variations in
      illumination, facial expression, pose, occlusion, etc. The main conclusions of
      this article are that two variants of the proposed fusion methodology surpass
      current face recognition methods and the classic fusion techniques reported in
      the literature, attaining recognition rates of over 97% and 99% for the Equinox
      and PUCV-VTF databases, respectively. The fusion methodology is very robust to
      illumination and expression changes, as it combines thermal and visible
      information efficiently by using genetic algorithms, thus allowing it to choose
      optimal face areas where one spectrum is more representative than the other. 

PMID- 26213933
TI  - Towards Semi-Automatic Artifact Rejection for the Improvement of Alzheimer's
      Disease Screening from EEG Signals.
AB  - A large number of studies have analyzed measurable changes that Alzheimer's
      disease causes on electroencephalography (EEG). Despite being easily
      reproducible, those markers have limited sensitivity, which reduces the interest
      of EEG as a screening tool for this pathology. This is for a large part due to
      the poor signal-to-noise ratio of EEG signals: EEG recordings are indeed usually
      corrupted by spurious extra-cerebral artifacts. These artifacts are responsible
      for a consequent degradation of the signal quality. We investigate the
      possibility to automatically clean a database of EEG recordings taken from
      patients suffering from Alzheimer's disease and healthy age-matched controls. We
      present here an investigation of commonly used markers of EEG artifacts:
      kurtosis, sample entropy, zero-crossing rate and fractal dimension. We
      investigate the reliability of the markers, by comparison with human labeling of
      sources. Our results show significant differences with the sample entropy marker.
      We present a strategy for semi-automatic cleaning based on blind source
      separation, which may improve the specificity of Alzheimer screening using EEG
      signals. 

PMID- 26213936
TI  - Energy-Efficient Channel Handoff for Sensor Network-Assisted Cognitive Radio
      Network.
AB  - The visiting and less-privileged status of the secondary users (SUs) in a
      cognitive radio network obligates them to release the occupied channel instantly
      when it is reclaimed by the primary user. The SU has a choice to make: either
      wait for the channel to become free, thus conserving energy at the expense of
      delayed transmission and delivery, or find and switch to a vacant channel,
      thereby avoiding delay in transmission at the expense of increased energy
      consumption. An energy-efficient decision that considers the tradeoff between
      energy consumption and continuous transmission needs to be taken as to whether to
      switch the channels. In this work, we consider a sensor network-assisted
      cognitive radio network and propose a backup channel, which is sensed by the SU
      in parallel with the operating channel that is being sensed by the sensor nodes.
      Imperfect channel sensing and residual energy of the SU are considered in order
      to develop an energy-efficient handoff strategy using the partially observable
      Markov decision process (POMDP), which considers beliefs about the operating and
      backup channels and the remaining energy of the SU in order to take an optimal
      channel handoff decision on the question "Should we switch the channel?" The
      objective is to dynamically decide in each time slot whether the SU should switch
      the channel or not in order to maximize throughput by utilizing energy
      efficiently. Extensive simulations were performed to show the effectiveness of
      the proposed channel handoff strategy, which was demonstrated in the form of
      throughput with respect to various parameters, i.e., detection probability, the
      channel idle probabilities of the operating and backup channels, and the maximum
      energy of the SU. 

PMID- 26213934
TI  - Zn(II)-Coordinated Quantum Dot-FRET Nanosensors for the Detection of Protein
      Kinase Activity.
AB  - We report a simple detection of protein kinase activity using Zn(II)-mediated
      fluorescent resonance energy transfer (FRET) between quantum dots (QDs) and dye
      tethered peptides. With neither complex chemical ligands nor surface modification
      of QDs, Zn(II) was the only metal ion that enabled the phosphorylated peptides to
      be strongly attached on the carboxyl groups of the QD surface via metal
      coordination, thus leading to a significant FRET efficiency. As a result, protein
      kinase activity in intermixed solution was efficiently detected by QD-FRET via
      Zn(II) coordination, especially when the peptide substrate was combined with
      affinity-based purification. We also found that mono- and di-phosphorylation in
      the peptide substrate could be discriminated by the Zn(II)-mediated QD-FRET. Our
      approach is expected to find applications for studying physiological function and
      signal transduction with respect to protein kinase activity. 

PMID- 26213935
TI  - Hyperspectral Analysis of Soil Total Nitrogen in Subsided Land Using the Local
      Correlation Maximization-Complementary Superiority (LCMCS) Method.
AB  - The measurement of soil total nitrogen (TN) by hyperspectral remote sensing
      provides an important tool for soil restoration programs in areas with subsided
      land caused by the extraction of natural resources. This study used the local
      correlation maximization-complementary superiority method (LCMCS) to establish TN
      prediction models by considering the relationship between spectral reflectance
      (measured by an ASD FieldSpec 3 spectroradiometer) and TN based on spectral
      reflectance curves of soil samples collected from subsided land which is
      determined by synthetic aperture radar interferometry (InSAR) technology. Based
      on the 1655 selected effective bands of the optimal spectrum (OSP) of the first
      derivate differential of reciprocal logarithm ([log{1/R}]'), (correlation
      coefficients, p < 0.01), the optimal model of LCMCS method was obtained to
      determine the final model, which produced lower prediction errors (root mean
      square error of validation [RMSEV] = 0.89, mean relative error of validation
      [MREV] = 5.93%) when compared with models built by the local correlation
      maximization (LCM), complementary superiority (CS) and partial least squares
      regression (PLS) methods. The predictive effect of LCMCS model was optional in
      Cangzhou, Renqiu and Fengfeng District. Results indicate that the LCMCS method
      has great potential to monitor TN in subsided lands caused by the extraction of
      natural resources including groundwater, oil and coal. 

PMID- 26213937
TI  - PEG Functionalization of Whispering Gallery Mode Optical Microresonator
      Biosensors to Minimize Non-Specific Adsorption during Targeted, Label-Free
      Sensing.
AB  - Whispering Gallery Mode (WGM) optical microresonator biosensors are a powerful
      tool for targeted detection of analytes at extremely low concentrations. However,
      in complex environments, non-specific adsorption can significantly reduce their
      signal to noise ratio, limiting their accuracy. To overcome this, poly(ethylene
      glycol) (PEG) can be employed in conjunction with appropriate recognition
      elements to create a nonfouling surface capable of detecting targeted analytes.
      This paper investigates a general route for the addition of nonfouling elements
      to WGM optical biosensors to reduce non-specific adsorption, while also retaining
      high sensitivity. We use the avidin-biotin analyte-recognition element system, in
      conjunction with PEG nonfouling elements, as a proof-of-concept, and explore the
      extent of non-specific adsorption of lysozyme and fibrinogen at multiple
      concentrations, as well as the ability to detect avidin in a concentration
      dependent fashion. Ellipsometry, contact angle measurement, fluorescence
      microscopy, and optical resonator characterization methods were used to study non
      specific adsorption, the quality of the functionalized surface, and the
      biosensor's performance. Using a recognition element ratio to nonfouling element
      ratio of 1:1, we showed that non-specific adsorption could be significantly
      reduced over the controls, and that high sensitivity could be maintained. Due to
      the frequent use of biotin-avidin-biotin sandwich complexes in functionalizing
      sensor surfaces with biotin-labeled recognition elements, this chemistry could
      provide a common basis for creating a non-fouling surface capable of targeted
      detection. This should improve the ability of WGM optical biosensors to operate
      in complex environments, extending their application towards real-world
      detection. 

PMID- 26213938
TI  - MOS-FET as a Current Sensor in Power Electronics Converters.
AB  - This paper presents a current sensing principle appropriate for use in power
      electronics' converters. This current measurement principle has been developed
      for metal oxide semiconductor field effect transistor (MOS-FET) and is based on
      U(DS) voltage measurement. In practice, shunt resistors and Hall effect sensors
      are usually used for these purposes, but the presented principle has many
      advantages. There is no need for additional circuit elements within high current
      paths, causing parasitic inductances and increased production complexity. The
      temperature dependence of MOS-FETs conductive resistance R(DS-ON) is considered
      in order to achieve the appropriate measurement accuracy. The "MOS-FET sensor" is
      also accompanied by a signal acquisition electronics circuit with an appropriate
      frequency bandwidth. The obtained analogue signal is therefore interposed to an A
      D converter for further data acquisition. In order to achieve sufficient
      accuracy, a temperature compensation and appropriate approximation is used (R(DS
      ON) = R(DS-ON)(thetaj)). The MOS-FET sensor is calibrated according to a
      reference sensor based on the Hall-effect principle. The program algorithm is
      executed on 32-bit ARM M4 MCU, STM32F407.

PMID- 26213939
TI  - Dynamic Reconfiguration of a RGBD Sensor Based on QoS and QoC Requirements in
      Distributed Systems.
AB  - The inclusion of embedded sensors into a networked system provides useful
      information for many applications. A Distributed Control System (DCS) is one of
      the clearest examples where processing and communications are constrained by the
      client's requirements and the capacity of the system. An embedded sensor with
      advanced processing and communications capabilities supplies high level
      information, abstracting from the data acquisition process and objects
      recognition mechanisms. The implementation of an embedded sensor/actuator as a
      Smart Resource permits clients to access sensor information through distributed
      network services. Smart resources can offer sensor services as well as computing,
      communications and peripheral access by implementing a self-aware based
      adaptation mechanism which adapts the execution profile to the context. On the
      other hand, information integrity must be ensured when computing processes are
      dynamically adapted. Therefore, the processing must be adapted to perform tasks
      in a certain lapse of time but always ensuring a minimum process quality. In the
      same way, communications must try to reduce the data traffic without excluding
      relevant information. The main objective of the paper is to present a dynamic
      configuration mechanism to adapt the sensor processing and communication to the
      client's requirements in the DCS. This paper describes an implementation of a
      smart resource based on a Red, Green, Blue, and Depth (RGBD) sensor in order to
      test the dynamic configuration mechanism presented. 

PMID- 26213940
TI  - Surface and Electrical Characterization of Ag/AgCl Pseudo-Reference Electrodes
      Manufactured with Commercially Available PCB Technologies.
AB  - Lab-on-Chip is a technology that could potentially revolutionize medical Point-of
      Care diagnostics. Considerable research effort is focused towards innovating
      production technologies that will make commercial upscaling financially viable.
      Printed circuit board manufacturing techniques offer several prospects in this
      field. Here, we present a novel approach to manufacturing Printed Circuit Board
      (PCB)-based Ag/AgCl reference electrodes, an essential component of biosensors.
      Our prototypes were characterized both structurally and electrically. Scanning
      Electron Microscopy (SEM) and X-Ray Photoelectron Spectroscopy (XPS) were
      employed to evaluate the electrode surface characteristics. Electrical
      characterization was performed to determine stability and pH dependency. Finally,
      we demonstrate utilization along with PCB pH sensors, as a step towards a fully
      integrated PCB platform, comparing performance with discrete commercial reference
      electrodes. 

PMID- 26213941
TI  - Air Temperature Error Correction Based on Solar Radiation in an Economical
      Meteorological Wireless Sensor Network.
AB  - Air temperature (AT) is an extremely vital factor in meteorology, agriculture,
      military, etc., being used for the prediction of weather disasters, such as
      drought, flood, frost, etc. Many efforts have been made to monitor the
      temperature of the atmosphere, like automatic weather stations (AWS).
      Nevertheless, due to the high cost of specialized AT sensors, they cannot be
      deployed within a large spatial density. A novel method named the meteorology
      wireless sensor network relying on a sensing node has been proposed for the
      purpose of reducing the cost of AT monitoring. However, the temperature sensor on
      the sensing node can be easily influenced by environmental factors. Previous
      research has confirmed that there is a close relation between AT and solar
      radiation (SR). Therefore, this paper presents a method to decrease the error of
      sensed AT, taking SR into consideration. In this work, we analyzed all of the
      collected data of AT and SR in May 2014 and found the numerical correspondence
      between AT error (ATE) and SR. This corresponding relation was used to calculate
      real-time ATE according to real-time SR and to correct the error of AT in other
      months. 

PMID- 26213942
TI  - On the Accuracy Potential in Underwater/Multimedia Photogrammetry.
AB  - Underwater applications of photogrammetric measurement techniques usually need to
      deal with multimedia photogrammetry aspects, which are characterized by the
      necessity of handling optical rays that are refracted at interfaces between
      optical media with different refractive indices according to Snell's Law. This so
      called multimedia geometry has to be incorporated into geometric models in order
      to achieve correct measurement results. The paper shows a flexible yet strict
      geometric model for the handling of refraction effects on the optical path, which
      can be implemented as a module into photogrammetric standard tools such as
      spatial resection, spatial intersection, bundle adjustment or epipolar line
      computation. The module is especially well suited for applications, where an
      object in water is observed by cameras in air through one or more planar glass
      interfaces, as it allows for some simplifications here. In the second part of the
      paper, several aspects, which are relevant for an assessment of the accuracy
      potential in underwater/multimedia photogrammetry, are discussed. These aspects
      include network geometry and interface planarity issues as well as effects caused
      by refractive index variations and dispersion and diffusion under water. All
      these factors contribute to a rather significant degradation of the geometric
      accuracy potential in underwater/multimedia photogrammetry. In practical
      experiments, a degradation of the quality of results by a factor two could be
      determined under relatively favorable conditions. 

PMID- 26213943
TI  - Insights on Capacitive Interdigitated Electrodes Coated with MOF Thin Films:
      Humidity and VOCs Sensing as a Case Study.
AB  - A prototypical metal-organic framework (MOF), a 2D periodic porous structure
      based on the assembly of copper ions and benzene dicarboxylate (bdc) ligands
      (Cu(bdc).xH2O), was grown successfully as a thin film on interdigitated
      electrodes (IDEs). IDEs have been used for achieving planar CMOS-compatible low
      cost capacitive sensing structures for the detection of humidity and volatile
      organic compounds (VOCs). Accordingly, the resultant IDEs coated with the
      Cu(bdc).xH2O thin film was evaluated, for the first time, as a capacitive sensor
      for gas sensing applications. A fully automated setup, using LabVIEW interfaces
      to experiment conduction and data acquisition, was developed in order to measure
      the associated gas sensing performance. 

PMID- 26213944
TI  - A Micro-Preconcentrator Combined Olfactory Sensing System with a Micromechanical
      Cantilever Sensor for Detecting 2,4-Dinitrotoluene Gas Vapor.
AB  - Preventing unexpected explosive attacks and tracing explosion-related molecules
      require the development of highly sensitive gas-vapor detection systems. For that
      purpose, a micromechanical cantilever-based olfactory sensing system including a
      sample preconcentrator was developed to detect 2,4-dinitrotoluene (2,4-DNT),
      which is a well-known by-product of the explosive molecule trinitrotoluene (TNT)
      and exists in concentrations on the order of parts per billion in the atmosphere
      at room temperature. A peptide receptor (His-Pro-Asn-Phe-Ser-Lys-Tyr-Ile-Leu-His
      Gln-Arg) that has high binding affinity for 2,4-DNT was immobilized on the
      surface of the cantilever sensors to detect 2,4-DNT vapor for highly selective
      detection. A micro-preconcentrator (uPC) was developed using Tenax-TA adsorbent
      to produce higher concentrations of 2,4-DNT molecules. The preconcentration was
      achieved via adsorption and thermal desorption phenomena occurring between target
      molecules and the adsorbent. The uPC directly integrated with a cantilever sensor
      and enhanced the sensitivity of the cantilever sensor as a pretreatment tool for
      the target vapor. The response was rapidly saturated within 5 min and sustained
      for more than 10 min when the concentrated vapor was introduced. By calculating
      preconcentration factor values, we verified that the cantilever sensor provides
      up to an eightfold improvement in sensing performance. 

PMID- 26213945
TI  - Twenty Years of Rad-Hard K14 SPAD in Space Projects.
AB  - During last two decades, several photon counting detectors have been developed in
      our laboratory. One of the most promising detector coming from our group silicon
      K14 Single Photon Avalanche Diode (SPAD) is presented with its valuable features
      and space applications. Based on the control electronics, it can be operated in
      both gated and non-gated mode. Although it was designed for photon counting
      detection, it can be employed for multiphoton detection as well. With respect to
      control electronics employed, the timing jitter can be as low as 20 ps RMS.
      Detection efficiency is about 40%in range of 500 nm to 800 nm. The detector
      including gating and quenching circuitry has outstanding timing stability. Due to
      its radiation resistivity, the diode withstands 100 krad gamma ray dose without
      parameters degradation. Single photon detectors based on K14 SPAD were used for
      planetary altimeter and atmospheric lidar in MARS92/96 and Mars Surveyor '98
      space projects, respectively. Recent space applications of K14 SPAD comprises
      LIDAR and mainly time transfer between ground stations and artificial satellites.
      These include Laser Time Transfer, Time Transfer by Laser Link, and European
      Laser Timing projects. 

PMID- 26213946
TI  - Colorimetric Sensor Array for White Wine Tasting.
AB  - A colorimetric sensor array was developed to characterize and quantify the taste
      of white wines. A charge-coupled device (CCD) camera captured images of the
      sensor array from 23 different white wine samples, and the change in the R, G, B
      color components from the control were analyzed by principal component analysis.
      Additionally, high performance liquid chromatography (HPLC) was used to analyze
      the chemical components of each wine sample responsible for its taste. A two
      dimensional score plot was created with 23 data points. It revealed clusters
      created from the same type of grape, and trends of sweetness, sourness, and
      astringency were mapped. An artificial neural network model was developed to
      predict the degree of sweetness, sourness, and astringency of the white wines.
      The coefficients of determination (R2) for the HPLC results and the sweetness,
      sourness, and astringency were 0.96, 0.95, and 0.83, respectively. This research
      could provide a simple and low-cost but sensitive taste prediction system, and,
      by helping consumer selection, will be able to have a positive effect on the wine
      industry. 

PMID- 26213947
TI  - Toxicological Studies of 212Pb Intravenously or Intraperitoneally Injected into
      Mice for a Phase 1 Trial.
AB  - Faced with the novelty of a 212Pb-labeled monoclonal antibody (mAb) for clinical
      translation, concerns were expressed by the Food and Drug Administration (FDA)
      regarding 212Pb prematurely released from the mAb-chelate conjugate. The
      objective of this study was to simulate the worst case scenario of such a
      failure. Groups of Balb/c mice (n = 9-20) were administered 212Pb by
      intraperitoneal (0.0925-1.85 MBq) or intravenous (0.0925-1.11 MBq) injection and
      then euthanized at 7 or 90 days to assess acute or chronic effects. Weights were
      recorded prior to injection of the 212Pb and at the end of the observation
      periods. Blood samples were collected for clinical chemistry and blood cell
      analysis. Thirty tissues were harvested and formalin fixed for histopathological
      examination. Treatment related effects of the 212Pb were observed in the bone
      marrow, spleen, kidneys and the liver. Histological alterations in these organs
      were considered mild to moderate, indicating low grade toxicity, and not
      considered severe enough to affect function. This data was presented to the FDA
      and determined to be acceptable. The clinical trial with 212Pb-TCMC-trastuzumab
      was approved in January 2011 and the trial opened at the University of Alabama at
      Birmingham (UAB) in July. 

PMID- 26213948
TI  - Chitinolytic Bacteria-Assisted Conversion of Squid Pen and Its Effect on Dyes and
      Pigments Adsorption.
AB  - The aim of this work was to produce chitosanase by fermenting from squid pen, and
      recover the fermented squid pen for dye removal by adsorption. One chitosanase
      induced from squid pen powder (SPP)-containing medium by Bacillus cereus TKU034
      was purified in high purification fold (441) and high yield of activity recovery
      (51%) by ammonium sulfate precipitation and combined column chromatography. The
      SDS-PAGE results showed its molecular mass to be around 43 kDa. The TKU034
      chitosanase used for the chitooligomers preparation was studied. The enzyme
      products revealed that the chitosanase could degrade chitosan with various
      degrees of polymerization, ranging from 3 to 9, as well as the chitosanase in an
      endolytic manner. Besides, the fermented SPP was recovered and displayed a better
      adsorption rate (up to 99.5%) for the disperse dyes (red, yellow, blue, and
      black) than the water-soluble food colorants, Allura Red AC (R40) and Tartrazine
      (Y4). The adsorbed R40 on the unfermented SPP and the fermented SPP was eluted by
      distilled water and 1 M NaOH to confirm the dye adsorption mechanism. The
      fermented SPP had a slightly higher adsorption capacity than the unfermented, and
      elution of the dye from the fermented SPP was easier than from the unfermented.
      The main dye adsorption mechanism of fermented SPP was physical adsorption, while
      the adsorption mechanism of unfermented SPP was chemical adsorption. 

PMID- 26213949
TI  - A Brief Review of Bioactive Metabolites Derived from Deep-Sea Fungi.
AB  - Deep-sea fungi, the fungi that inhabit the sea and the sediment at depths of over
      1000 m below the surface, have become an important source of industrial,
      agricultural, and nutraceutical compounds based on their diversities in both
      structure and function. Since the first study of deep-sea fungi in the Atlantic
      Ocean at a depth of 4450 m was conducted approximately 50 years ago, hundreds of
      isolates of deep-sea fungi have been reported based on culture-dependent methods.
      To date more than 180 bioactive secondary metabolites derived from deep-sea fungi
      have been documented in the literature. These include compounds with anticancer,
      antimicrobial, antifungal, antiprotozoal, and antiviral activities. In this
      review, we summarize the structures and bioactivities of these metabolites to
      provide help for novel drug development. 

PMID- 26213950
TI  - Physico-Chemical and Microbial Analysis of Selected Borehole Water in Mahikeng,
      South Africa.
AB  - Groundwater is generally considered a "safe source" of drinking water because it
      is abstracted with low microbial load with little need for treatment before
      drinking. However, groundwater resources are commonly vulnerable to pollution,
      which may degrade their quality. An assessment of microbial and physicochemical
      qualities of borehole water in the rural environs of Mahikeng town, South Africa,
      was carried out. The study aimed at determining levels of physicochemical
      (temperature, pH, turbidity and nitrate) and bacteriological (both faecal and
      total coliform bacteria) contaminants in drinking water using standard
      microbiology methods. Furthermore, identities of isolates were determined using
      the API 20E assay. Results were compared with World Health Organisation (WHO) and
      Department of Water Affairs (DWAF-SA) water quality drinking standards. All
      analyses for physicochemical parameters were within acceptable limits except for
      turbidity while microbial loads during spring were higher than the WHO and DWAF
      thresholds. The detection of Escherichia coli, Salmonella and Klebsiella species
      in borehole water that was intended for human consumption suggests that water
      from these sources may pose severe health risks to consumers and is unsuitable
      for direct human consumption without treatment. The study recommends mobilisation
      of onsite treatment interventions to protect the households from further possible
      consequences of using the water. 

PMID- 26213951
TI  - Effect of Temperature on Fimbrial Gene Expression and Adherence of
      Enteroaggregative Escherichia coli.
AB  - The influence of temperature on bacterial virulence has been studied worldwide
      from the viewpoint of climate change and global warming. The bacterium
      enteroaggregative Escherichia coli (EAEC) is the causative agent of watery
      diarrhea and shows an increasing incidence worldwide. Its pathogenicity is
      associated with the virulence factors aggregative adherence fimbria type I and II
      (AAFI and AAFII), encoded by aggA and aafA in EAEC strains 17-2 and 042,
      respectively. This study focused on the effect of temperature increases from 29 
      degrees C to 40  degrees C on fimbrial gene expression using real-time PCR, and
      on its virulence using an aggregative adherence assay and biofilm formation
      assay. Incubation at 32  degrees C caused an up-regulation in both EAEC strains
      17-2 and strain 042 virulence gene expression. EAEC strain 042 cultured at
      temperature above 32  degrees C showed down-regulation of aafA expression except
      at 38  degrees C. Interestingly, EAEC cultured at a high temperature showed a
      reduced adherence to cells and an uneven biofilm formation. These results provide
      evidence that increases in temperature potentially affect the virulence of
      pathogenic EAEC, although the response varies in each strain. 

PMID- 26213952
TI  - Experience of Multisensory Environments in Public Space among People with Visual
      Impairment.
AB  - This qualitative study explored the role of sensory characteristics embedded in
      the built environment and whether they support or hinder people with visual
      impairment in their use of public spaces. An online survey link was e-mailed to
      the presidents and committee members of each state's chapters and associations of
      the National Federation of the Blind in the United States, resulting in 451
      direct invitations to participate. Written responses of the survey questions from
      48 respondents with visual impairment were analyzed. Three main themes: Barriers,
      Supporters, and Context-Dependence emerged from the respondents' experience of
      multisensory characteristics within the built environment. The four subthemes
      subsumed in Barriers were: (1) Population specific design, (2) Extreme sensory
      backgrounds, (3) Uneven ground surfaces and objects, and (4) Inconsistent
      lighting. For Supporters, respondents provided specific examples of various
      sensory characteristics in built environments, including audible cues and echoes,
      smells, tactile quality of the ground surface, and temperature. Context
      Dependence referred to the effects of sensory characteristics embedded in public
      spaces depending on one's vision condition, the proximity to the sensory cues and
      the purpose of the activities one was performing at that moment. Findings provide
      occupational therapy practitioners an in-depth understanding of the transactional
      relationship between embedded sensory characteristics in the built environment,
      occupations, and people with visual impairment in order to make appropriate
      modifications or removal of barriers that affect occupational performance and
      engagement. Suggestions for occupational therapists as well as architects,
      designers, planners, policy makers/legislators related to functional sensory cues
      in the design of built environments were provided to increase accessibility in
      the use of public spaces by people with visual impairment. 

PMID- 26213953
TI  - Effect of Disinfectants on Preventing the Cross-Contamination of Pathogens in
      Fresh Produce Washing Water.
AB  - The potential cross-contamination of pathogens between clean and contaminated
      produce in the washing tank is highly dependent on the water quality. Process
      wash water disinfectants are applied to maintain the water quality during
      processing. The review examines the efficacy of process wash water disinfectants
      during produce processing with the aim to prevent cross-contamination of
      pathogens. Process wash water disinfection requires short contact times so
      microorganisms are rapidly inactivated. Free chlorine, chlorine dioxide, ozone,
      and peracetic acid were considered suitable disinfectants. A disinfectant's
      reactivity with the organic matter will determine the disinfectant residual,
      which is of paramount importance for microbial inactivation and should be
      monitored in situ. Furthermore, the chemical and worker safety, and the
      legislative framework will determine the suitability of a disinfection technique.
      Current research often focuses on produce decontamination and to a lesser extent
      on preventing cross-contamination. Further research on a sanitizer's efficacy in
      the washing water is recommended at the laboratory scale, in particular with
      experimental designs reflecting industrial conditions. Validation on the
      industrial scale is warranted to better understand the overall effects of a
      sanitizer. 

PMID- 26213954
TI  - Evaluation of Combined Disinfection Methods for Reducing Escherichia coli O157:H7
      Population on Fresh-Cut Vegetables.
AB  - Most current disinfection strategies for fresh-cut industry are focused on the
      use of different chemical agents; however, very little has been reported on the
      effectiveness of the hurdle technology. The effect of combined decontamination
      methods based on the use of different sanitizers (peroxyacetic acid and chlorine
      dioxide) and the application of pressure (vacuum/positive pressure) on the
      inactivation of the foodborne pathogen E. coli O157:H7 on fresh-cut lettuce
      (Lactuca sativa) and carrots (Daucus carota) was studied. Fresh produce,
      inoculated with E. coli O157:H7, was immersed (4  degrees C, 2 min) in tap water
      (W), chlorine water (CW), chlorine dioxide (ClO2: 2 mg/L) and peroxyacetic acid
      (PAA: 100 mg/L) in combination with: (a) vacuum (V: 10 mbar) or (b) positive
      pressure application (P: 3 bar). The product quality and antimicrobial effects of
      the treatment on bacterial counts were determined both in process washing water
      and on fresh-cut produce. Evidence obtained in this study, suggests that the use
      of combined methods (P/V + sanitizers) results in a reduction on the
      microorganism population on produce similar to that found at atmospheric
      pressure. Moreover, the application of physical methods led to a significant
      detrimental effect on the visual quality of lettuce regardless of the solution
      used. Concerning the process water, PAA proved to be an effective alternative to
      chlorine for the avoidance of cross-contamination. 

PMID- 26213955
TI  - The Impact of Ambient Temperature on Childhood HFMD Incidence in Inland and
      Coastal Area: A Two-City Study in Shandong Province, China.
AB  - Hand, foot and mouth disease (HFMD) has been a substantial burden throughout the
      Asia-Pacific countries over the past decades. For the purposes of disease
      prevention and climate change health impact assessment, it is important to
      understand the temperature-disease association for HFMD in different geographical
      locations. This study aims to assess the impact of temperature on HFMD incidence
      in an inland city and a coastal city and investigate the heterogeneity of
      temperature-disease associations. Daily morbidity data and meteorological
      variables of the study areas were collected for the period from 2007 to 2012. A
      total of 108,377 HFMD cases were included in this study. A distributed lag non
      linear model (DLNM) with Poisson distribution was used to examine the nonlinear
      lagged effects of daily mean temperature on HFMD incidence. After controlling
      potential confounders, temperature showed significant association with HFMD
      incidence and the two cities demonstrated different impact modes ( I2= 96.1%; p <
      0.01). The results highlight the effect of temperature on HFMD incidence and the
      impact pattern may be modified by geographical localities. Our findings can be a
      practical reference for the early warning and intervention strategies of HFMD. 

PMID- 26213956
TI  - Impact of National Smoke-Free Legislation on Educational Disparities in Smoke
      Free Homes: Findings from the SIDRIAT Longitudinal Study.
AB  - Families with lower socioeconomic status are less likely to adopt household
      smoking bans (HSB). The aim of this study was to determine whether socioeconomic
      disparities in HSB prevalence in Italy decreased 7-9 years after the introduction
      of the Italian ban on smoking in public places. A longitudinal, 12-year, two-wave
      study was conducted on a sample of 3091 youths aged 6-14 years in 2002; 1763
      (57%) were re-interviewed in 2012-2014. A Poisson regression with a robust error
      variance was used to assess the association between socioeconomic disparities and
      HSB prevalence. The adoption of HSBs significantly increased from 60% in 2002 to
      75% in 2012-2014, with the increase recorded in youths with >=1 smoking parent
      only (from 22% at baseline to 46% at follow-up). The presence of HSBs at baseline
      was more likely in families with >=1 graduate parent compared to those with no
      graduate parents (prevalence ratio (PR) = 1.34, 95% confidence interval (CI) =
      1.15-1.57), either in families with >=1 smoking parent (PR = 1.36, 95% CI = 1.17
      1.58) or in families with non-smoking parents (PR = 1.61, 95% CI = 1.01-2.56).
      Conversely, at follow-up socioeconomic disparities dropped since families with no
      graduate parents were 1.5-fold more likely to introduce a HSB between the two
      waves. The Italian ban on smoking in public places may have increased the
      adoption of smoke-free homes in families with smoking and non-graduate parents,
      causing the drop of the socioeconomic gap in smoke-free homes. 

PMID- 26213957
TI  - Inventory of Engineered Nanoparticle-Containing Consumer Products Available in
      the Singapore Retail Market and Likelihood of Release into the Aquatic
      Environment.
AB  - Consumer products containing engineered nanoparticles (ENP) are already entering
      the marketplace. This leads, inter alia, to questions about the potential for
      release of ENP into the environment from commercial products. We have inventoried
      the prevalence of ENP-containing consumer products in the Singapore market by
      carrying out onsite assessments of products sold in all major chains of retail
      and cosmetic stores. We have assessed their usage patterns and estimated release
      factors and emission quantities to obtain a better understanding of the
      quantities of ENP that are released into which compartments of the aquatic
      environment in Singapore. Products investigated were assessed for their
      likelihood to contain ENP based on the declaration of ENP by producers, feature
      descriptions, and the information on particle size from the literature. Among the
      1,432 products investigated, 138 were "confirmed" and 293 were "likely" to
      contain ENP. Product categories included sunscreens, cosmetics, health and
      fitness, automotive, food, home and garden, clothing and footwear, and
      eyeglass/lens coatings. Among the 27 different types of nanomaterials identified,
      SiO2 was predominant, followed by TiO2 and ZnO, Carbon Black, Ag, and Au. The
      amounts of ENP released into the aquatic system, which was estimated on the basis
      of typical product use, ENP concentration in the product, daily use quantity,
      release factor, and market share, were in the range of several hundred tons per
      year. As these quantities are likely to increase, it will be important to further
      study the fate of ENP that reach the aquatic environment in Singapore. 

PMID- 26213958
TI  - Injury Risk Factors in a Small-Scale Gold Mining Community in Ghana's Upper East
      Region.
AB  - Occupational injury is one of many health concerns related to small-scale gold
      mining (ASGM), but few data exist on the subject, especially in sub-Saharan
      Africa. In 2011 and 2013, we examined accidents, injuries, and potential risk
      factors in a Ghanaian ASGM community. In 2011, 173 participants were surveyed on
      occupational history and health, and 22 of these were surveyed again in 2013.
      Injury rates were estimated at 45.5 and 38.5 injuries per 100 person-years in
      2011 and in 2013, respectively; these rates far surpass those of industrialized
      mines in the U.S. and South Africa. Demographic and job characteristics generally
      were not predictive of injury risk, though there was a significant positive
      association with injury risk for males and smokers. Legs and knees were the most
      common body parts injured, and falling was the most common cause of injury. The
      most common type of injuries were cuts or lacerations, burns and scalds, and
      contusions and abrasions. Only two miners had ever received any occupational
      safety training, and PPE use was low. Our results suggest that injuries should be
      a priority area for occupational health research in ASGM. 

PMID- 26213959
TI  - Long-Term Effectiveness of Antiretroviral Therapy in China: An Observational
      Cohort Study from 2003-2014.
AB  - In order to assess the effectiveness of the Chinese government's expanded access
      program, a cohort study on all adult HIV patients in Shenzhen was conducted from
      December 2003 to February 2014 to estimate the effects of antiretroviral therapy
      (ART) on mortality, tuberculosis and CD4 cell counts. Marginal structural
      regression models adjusted for baseline and time-varying covariates. Of the 6897
      patients enrolled and followed up for a maximum of 178 months, 44.92% received
      ART. Among patients who commenced receiving ART during the study, there were 98
      deaths and 59 new tuberculosis diagnoses, while there were 410 deaths and 201 new
      tuberculosis diagnoses among those without ART. ART was associated with both
      lower mortality (hazard ratio [HR] = 0.18; 95% confidence interval [CI] = 0.11
      0.27) and the presence of tuberculosis (HR = 0.27; 95% CI = 0.19-0.37). Each
      month of ART was associated with an average increase in CD4 cell count of 6.52
      cells/uL (95% CI = 6.08-7.12 cells/uL). In conclusions, the effectiveness of ART
      provided by China government health services is the same as that in higher-income
      countries. Accounting to higher mortality rates from the delay of starting ART,
      faster expansion and timely imitation of ART are urgent. 

PMID- 26213960
TI  - Screening of mRNA Chemical Modification to Maximize Protein Expression with
      Reduced Immunogenicity.
AB  - Chemical modification of nucleosides in mRNA is an important technology to
      regulate the immunogenicity of mRNA. In this study, various previously reported
      mRNA formulations were evaluated by analyzing in vitro protein expression and
      immunogenicity in multiple cell lines. For the macrophage-derived cell line, RAW
      264.7, modified mRNA tended to have reduced immunogenicity and increased protein
      expression compared to the unmodified mRNA. In contrast, in some cell types, such
      as hepatocellular carcinoma cells (HuH-7) and mouse embryonic fibroblasts (MEFs),
      protein expression was decreased by mRNA modification. Further analyses revealed
      that mRNA modifications decreased translation efficiency but increased nuclease
      stability. Thus, mRNA modification is likely to exert both positive and negative
      effects on the efficiency of protein expression in transfected cells and optimal
      mRNA formulation should be determined based on target cell types and transfection
      purposes. 

PMID- 26213961
TI  - Highly Effective Non-Viral Antitumor Gene Therapy System Comprised of
      Biocompatible Small Plasmid Complex Particles Consisting of pDNA, Anionic
      Polysaccharide, and Fully Deprotected Linear Polyethylenimine.
AB  - We have reported that ternary complexes of plasmid DNA with conventional linear
      polyethylenimine (l-PEI) and certain polyanions were very stably dispersed, and,
      with no cryoprotectant, they could be freeze-dried and re-hydrated without the
      loss of transfection ability. These properties enabled the preparation of a
      concentrated suspension of very small pDNA complex, by preparing the complexes at
      highly diluted conditions, followed by condensation via lyophilization-and
      rehydration procedure. Recently, a high potency linear polyethylenimine having no
      residual protective groups, i.e., Polyethylenimine "Max" (PEI "Max"), is
      available, which has been reported to induce much higher gene expression than
      conventional l-PEI. We tried to prepare the small DNA/PEI "Max"/polyanion
      complexes by a similar freeze-drying method. Small complex particles could be
      obtained without apparent aggregation, but transfection activity of the
      rehydrated complexes was severely reduced. Complex-preparation conditions were
      investigated in details to achieve the freeze-dried DNA/PEI "Max"/polyanion small
      ternary complexes with high transfection efficiency. DNA/PEI "Max"/polyanion
      complexes containing cytokine-coding plasmids were then prepared, and their anti
      tumor therapeutic efficacy was examined in tumor-bearing mice. 

PMID- 26213962
TI  - Novel Antitumor Strategy Utilizing a Plasmid Expressing a Mycobacterium
      tuberculosis Antigen as a "Danger Signal" to Block Immune Escape of Tumor Cells.
AB  - Immune escape of tumor cells is one of the main obstacles hindering the
      effectiveness of cancer immunotherapy. We developed a novel strategy to block
      immune escape by transfecting tumor cells in vivo with genes of pathogenic
      antigens from Mycobacterium tuberculosis (TB). This induces presentation of the
      TB antigen on tumor cell surfaces, which can be recognized by antigen presenting
      cells (APCs) as a "danger signal" to stimulate antitumor immune response. This
      strategy is also expected to amplify the immune response against tumor-associated
      antigens, and block immune escape of the tumor. DNA/PEI/chondroitin sulfate
      ternary complex is a highly effective non-viral gene vector system for in vivo
      transfection. A therapeutic complex was prepared using a plasmid encoding the TB
      antigen, early secretory antigenic target-6 (ESAT-6). This was injected
      intratumorally into syngeneic tumor-bearing mice, and induced significant tumor
      growth suppression comparable to or higher than similar complexes expressing
      cytokines such as interleukin-2 (IL-2) and interleukin-12 (IL-12). Co
      transfection of the cytokine-genes and the ESAT-6-gene enhanced the antitumor
      efficacy of either treatment alone. In addition, complete tumor regression was
      achieved with the combination of ESAT-6 and IL-2 genes. 

PMID- 26213963
TI  - Higher Body Iron Is Associated with Greater Depression Symptoms among Young Adult
      Men but not Women: Observational Data from the Daily Life Study.
AB  - Studies investigating possible associations between iron status and mood or
      depressive symptoms have reported inconsistent results. However, they have
      neither used body iron to measure iron status nor measured mood using daily
      measures. We investigated whether body iron was associated with depressive
      symptoms, daily mood, daily tiredness, difficulty concentrating, and stress in
      young adult women and men. Young adult (17-25 years) women (n = 562) and men (n =
      323) completed the Center for Epidemiologic Studies Depression Scale, then
      reported negative and positive mood, and other states daily for 13 days. Non
      fasting venous blood was collected to determine hemoglobin, serum ferritin and
      soluble transferrin receptor (to calculate body iron), C-reactive protein, and
      alpha-1-acid glycoprotein concentration. Regression models tested linear
      associations between body iron and the outcome variables, controlling for
      possible confounders. No associations were found between body iron and the
      outcome variables in women. However, higher body iron was associated with more
      depressive symptoms in men (3.4% more per body iron mg/kg; 95% confidence
      intervals (CI): 0.8%, 5.9%). In young adult women, body iron is unlikely to be
      associated with significant deficits in mood or depressive symptoms. However,
      higher body iron may be associated with more depressive symptoms in young adult
      men. 

PMID- 26213964
TI  - Consumption Patterns of Fruit and Vegetable Juices and Dietary Nutrient Density
      among French Children and Adults.
AB  - BACKGROUND: Fruit and vegetable consumption is a marker of higher-quality diets;
      less is known about the contribution of 100% fruit and vegetable juices (FVJ) to
      diet quality. OBJECTIVE: To explore FVJ consumption patterns in relation to
      dietary nutrient density among French children (aged 3-14 years old) and adults
      (>=21 years old). METHODS: Analyses were based on the nationally representative
      2013 CCAF (Comportements et Consommations Alimentaires en France) survey of 1930
      respondents, stratified by age group, FVJ consumption, and socioeconomic status
      (SES). Dietary nutrient density was based on the Nutrient Rich Food (NRF9.3)
      index, adjusted for gender and age. RESULTS: Mean total consumption of fruits and
      vegetables was 2.6 servings/day for children and 3.8 servings/day for adults.
      Mean population consumption of FVJ was 83 mL/day for children and 54.6 mL/day for
      adults, equivalent to 0.4 servings/day and 0.3 servings/day respectively. FVJ
      consumers had higher quality diets than did non-consumers, after adjusting for
      covariates. The respective NRF9.3 values were 486.4 +/- 4.3 vs. 428.7 +/- 7.5 for
      children and 460.7 +/- 4.4 vs. 435.4 +/- 4.4 for adults. FVJ consumers had
      similar or higher intakes of fruits and vegetables than did non-consumers. The
      socioeconomic gradient for FVJ consumption was much weaker (p < 0.046) than for
      whole fruit (p < 0.01). CONCLUSIONS: In a nationally representative sample of
      French children and adults, fruit and vegetable consumption fell short of
      recommended values. Higher FVJ consumption was associated with higher-quality
      diets and better compliance with the French National Plan for Nutrition and
      Health (PNNS).

PMID- 26213965
TI  - Molecular Cloning and Functional Analysis of Gene Clusters for the Biosynthesis
      of Indole-Diterpenes in Penicillium crustosum and P. janthinellum.
AB  - The penitremane and janthitremane families of indole-diterpenes are abundant
      natural products synthesized by Penicillium crustosum and P. janthinellum. Using
      a combination of PCR, cosmid library screening, and Illumina sequencing we have
      identified gene clusters encoding enzymes for the synthesis of these compounds.
      Targeted deletion of penP in P. crustosum abolished the synthesis of penitrems A,
      B, D, E, and F, and led to accumulation of paspaline, a key intermediate for
      paxilline biosynthesis in P. paxilli. Similarly, deletion of janP and janD in P.
      janthinellum abolished the synthesis of prenyl-elaborated indole-diterpenes, and
      led to accumulation in the latter of 13-desoxypaxilline, a key intermediate for
      the synthesis of the structurally related aflatremanes synthesized by Aspergillus
      flavus. This study helps resolve the genetic basis for the complexity of indole
      diterpene natural products found within the Penicillium and Aspergillus species.
      All indole-diterpene gene clusters identified to date have a core set of genes
      for the synthesis of paspaline and a suite of genes encoding multi-functional
      cytochrome P450 monooxygenases, FAD dependent monooxygenases, and prenyl
      transferases that catalyse various regio- and stereo- specific oxidations that
      give rise to the diversity of indole-diterpene products synthesized by this group
      of fungi. 

PMID- 26213966
TI  - Functional Characterization of New Polyketide Synthase Genes Involved in
      Ochratoxin A Biosynthesis in Aspergillus Ochraceus fc-1.
AB  - Ochratoxin A (OTA), a potentially carcinogenic mycotoxin which contaminates
      grains, is produced by several Aspergillus species. A comparative sequence
      analysis of the OTA-producing Aspergillus ochraceus fc-1 strain and other
      Aspergillus species was performed. Two new OTA-related polyketide synthase (PKS)
      (AoOTApks) genes were identified. The predicted amino acid sequence of AoOTApks-1
      displayed high similarity to previously identified PKSs from OTA-producing A.
      carbonarius ITEM 5010 (67%; [PI] No. 173482) and A. niger CBS 513.88 (62%;
      XP_001397313). However, the predicted amino acid sequence of AoOTApks-2 displayed
      lower homology with A. niger CBS 513.88 (38%) and A. carbonarius ITEM 5010 (28%).
      A phylogenetic analysis of the beta-ketosynthase and acyl-transferase domains of
      the AoOTApks proteins indicated that they shared a common origin with other OTA
      producing species, such as A. carbonarius, A. niger, and A. westerdijkiae. A real
      time reverse-transcription PCR analysis showed that the expression of AoOTApks-1
      and -2 was positively correlated with the OTA concentration. The pks gene deleted
      mutants ?AoOTApks-1 and ?AoOTApks-2 produced nil and lesser OTA than the wild
      type strain, respectively. Our study suggests that AoOTApks-1 could be involved
      in OTA biosynthesis, while AoOTApks-2 might be indirectly involved in OTA
      production. 

PMID- 26213967
TI  - Acetylcholinesterase in Biofouling Species: Characterization and Mode of Action
      of Cyanobacteria-Derived Antifouling Agents.
AB  - Effective and ecofriendly antifouling (AF) compounds have been arising from
      naturally produced chemicals. The objective of this study is to use cyanobacteria
      derived agents to investigate the role of acetylcholinesterase (AChE) activity as
      an effect and/or mode of action of promising AF compounds, since AChE inhibitors
      were found to inhibit invertebrate larval settlement. To pursue this objective,
      in vitro quantification of AChE activity under the effect of several
      cyanobacterial strain extracts as potential AF agents was performed along with in
      vivo AF (anti-settlement) screening tests. Pre-characterization of different
      cholinesterases (ChEs) forms present in selected tissues of important biofouling
      species was performed to confirm the predominance of AChE, and an in vitro AF
      test using pure AChE activity was developed. Eighteen cyanobacteria strains were
      tested as source of potential AF and AChE inhibitor agents. Results showed
      effectiveness in selecting promising eco-friendly AF agents, allowing the
      understanding of the AF biochemical mode of action induced by different
      compounds. This study also highlights the potential of cyanobacteria as source of
      AF agents towards invertebrate macrofouling species. 

PMID- 26213968
TI  - The Father, Son and Cholix Toxin: The Third Member of the DT Group Mono-ADP
      Ribosyltransferase Toxin Family.
AB  - The cholix toxin gene (chxA) was first identified in V. cholerae strains in 2007,
      and the protein was identified by bioinformatics analysis in 2008. It was
      identified as the third member of the diphtheria toxin group of mono-ADP
      ribosyltransferase toxins along with P. aeruginosa exotoxin A and C. diphtheriae
      diphtheria toxin. Our group determined the structure of the full-length, three
      domain cholix toxin at 2.1 A and its C-terminal catalytic domain (cholixc) at
      1.25 A resolution. We showed that cholix toxin is specific for elongation factor
      2 (diphthamide residue), similar to exotoxin A and diphtheria toxin. Cholix toxin
      possesses molecular features required for infection of eukaryotes by receptor
      mediated endocytosis, translocation to the host cytoplasm and inhibition of
      protein synthesis. More recently, we also solved the structure of full-length
      cholix toxin in complex with NAD+ and proposed a new kinetic model for cholix
      enzyme activity. In addition, we have taken a computational approach that
      revealed some important properties of the NAD+-binding pocket at the residue
      level, including the role of crystallographic water molecules in the NAD+
      substrate interaction. We developed a pharmacophore model of cholix toxin, which
      revealed a cationic feature in the side chain of cholix toxin active-site
      inhibitors that may determine the active pose. Notably, several recent reports
      have been published on the role of cholix toxin as a major virulence factor in V.
      cholerae (non-O1/O139 strains). Additionally, FitzGerald and coworkers prepared
      an immunotoxin constructed from domains II and III as a cancer treatment strategy
      to complement successful immunotoxins derived from P. aeruginosa exotoxin A. 

PMID- 26213969
TI  - Deoxynivalenol & Deoxynivalenol-3-Glucoside Mitigation through Bakery Production
      Strategies: Effective Experimental Design within Industrial Rusk-Making
      Technology.
AB  - In the scientific field, there is a progressive awareness about the potential
      implications of food processing on mycotoxins especially concerning thermal
      treatments. High temperatures may cause, in fact, transformation or degradation
      of these compounds. This work is aimed to study the fate of mycotoxins during
      bakery processing, focusing on deoxynivalenol (DON) and deoxynivalenol-3
      glucoside (DON3Glc), along the chain of industrial rusk production. Starting from
      naturally contaminated bran, we studied how concentrations of DON and DON3Glc are
      influenced by modifying ingredients and operative conditions. The experiments
      were performed using statistical Design of Experiment (DoE) schemes to
      synergistically explore the relationship between mycotoxin reduction and the
      indicated processing transformation parameters. All samples collected during
      pilot plant experiments were analyzed with an LC-MS/MS multimycotoxin method. The
      obtained model shows a good fitting, giving back relevant information in terms of
      optimization of the industrial production process, in particular suggesting that
      time and temperature in baking and toasting steps are highly relevant for
      minimizing mycotoxin level in rusks. A reduction up to 30% for DON and DON3Glc
      content in the finished product was observed within an acceptable technological
      range. 

PMID- 26213970
TI  - Temporomandibular Myofacial Pain Treated with Botulinum Toxin Injection.
AB  - This article reviews the diagnoses and treatment of temporomandibular disorders
      (TMD) and outlines of the role of botulinum toxin (BoNT) in the treatment of
      myofacial TMD. This manuscript includes a brief history of the use of BoNT in the
      treatment of pain, the mechanism of action of BoNT, and the techniques for
      injections, adverse effects and contraindications when using BoNT to treat
      mayofacial pain caused by TMD. 

PMID- 26213971
TI  - Vitamins and Melanoma.
AB  - A tremendous amount of information was published over the past decades in
      relation to the role of vitamins in various neoplastic diseases. In particular,
      several studies showed an inverse relationship between selected vitamins intake
      and cancer risk. In this review we will focus on the role played by vitamins in
      melanoma with particular regard to vitamin A, D, K, E and C. Given that vitamin
      supplementation is easy, convenient, and readily accepted by patients, in the
      future the use of vitamins in chemoprevention and therapy of melanoma could be
      encouraged if supported by pre-clinical and clinical evidence. 

PMID- 26213972
TI  - Complete Genomic Characterization of Porcine Reproductive and Respiratory
      Syndrome Virus Strain HB-XL.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is the causal agent
      of a serious disease of swine. Here, we report the genome sequence of PRRSV
      strain HB-XL isolated from a pig farm with a clinical outbreak of porcine
      reproductive and respiratory syndrome. The genome is 15,323 bp long and has nine
      open reading frames (GenBank: KP162169). Comparative and phylogenetic analysis
      showed that HB-XL belongs to the highly pathogenic PRRSV (HP-PRRSV) subfamily in
      the family PRRSV. The viral nonstructural protein 2 (Nsp2) of the HB-XL strain
      contained 30 discontinuous amino acid (AA) deletions relative to that of the Nsp2
      of the VR2332 strain. The AA substitutions R13 and R151 suggested high virulence
      of the HB-XL strain. The unique mutations in glycoprotein 5 (GP5) and Nsp2
      revealed that HB-XL might be a novel variant PRRSV strain recombined with vaccine
      strains. However, the low morbidity and mortality in the pig herd from which HB
      XL was isolated indicate that the virulence of the virus was weak, so it has
      potential as a future vaccine strain. 

PMID- 26213974
TI  - Full Genome Sequence Analysis of Two Isolates Reveals a Novel Xanthomonas Species
      Close to the Sugarcane Pathogen Xanthomonas albilineans.
AB  - Xanthomonas albilineans is the bacterium responsible for leaf scald, a lethal
      disease of sugarcane. Within the Xanthomonas genus, X. albilineans exhibits
      distinctive genomic characteristics including the presence of significant genome
      erosion, a non-ribosomal peptide synthesis (NRPS) locus involved in albicidin
      biosynthesis, and a type 3 secretion system (T3SS) of the Salmonella
      pathogenicity island-1 (SPI-1) family. We sequenced two X. albilineans-like
      strains isolated from unusual environments, i.e., from dew droplets on sugarcane
      leaves and from the wild grass Paspalum dilatatum, and compared these genomes
      sequences with those of two strains of X. albilineans and three of Xanthomonas
      sacchari. Average nucleotide identity (ANI) and multi-locus sequence analysis
      (MLSA) showed that both X. albilineans-like strains belong to a new species close
      to X. albilineans that we have named "Xanthomonas pseudalbilineans". X.
      albilineans and "X. pseudalbilineans" share many genomic features including (i)
      the lack of genes encoding a hypersensitive response and pathogenicity type 3
      secretion system (Hrp-T3SS), and (ii) genome erosion that probably occurred in a
      common progenitor of both species. Our comparative analyses also revealed
      specific genomic features that may help X. albilineans interact with sugarcane,
      e.g., a PglA endoglucanase, three TonB-dependent transporters and a glycogen
      metabolism gene cluster. Other specific genomic features found in the "X.
      pseudalbilineans" genome may contribute to its fitness and specific ecological
      niche. 

PMID- 26213973
TI  - The Structural Determinants behind the Epigenetic Role of Histone Variants.
AB  - Histone variants are an important part of the histone contribution to chromatin
      epigenetics. In this review, we describe how the known structural differences of
      these variants from their canonical histone counterparts impart a chromatin
      signature ultimately responsible for their epigenetic contribution. In terms of
      the core histones, H2A histone variants are major players while H3 variant CenH3,
      with a controversial role in the nucleosome conformation, remains the genuine
      epigenetic histone variant. Linker histone variants (histone H1 family) haven't
      often been studied for their role in epigenetics. However, the micro
      heterogeneity of the somatic canonical forms of linker histones appears to play
      an important role in maintaining the cell-differentiated states, while the cell
      cycle independent linker histone variants are involved in development. A picture
      starts to emerge in which histone H2A variants, in addition to their individual
      specific contributions to the nucleosome structure and dynamics, globally impair
      the accessibility of linker histones to defined chromatin locations and may have
      important consequences for determining different states of chromatin metabolism. 

PMID- 26213975
TI  - Neutrophils Do Not Express IL-17A in the Context of Acute Oropharyngeal
      Candidiasis.
AB  - IL-17 protects against pathogens by acting on nonhematopoietic cells to induce
      neutrophil recruitment through upregulation of chemokines and G-CSF. IL-17- and
      Th17-deficient humans and mice are susceptible to mucosal Candida albicans
      infections, linked to impaired neutrophil responses. IL-17 production is
      traditionally associated with CD4+ Th17 cells. However, IL-17 is also expressed
      during innate responses to facilitate rapid pathogen clearance. Innate IL-17
      expressing cells include various lymphocyte-type subsets, including ILC3, NKT,
      gammadelta-T and "natural" Th17 (nTh17) cells. Some reports suggest that
      neutrophils can express IL-17 during fungal infections. Here, we asked whether
      neutrophils serve as a source of IL-17 during acute oropharyngeal candidiasis
      (OPC) using an IL-17A fate-tracking reporter mouse. Mice were subjected to OPC
      for two days, and oral tissue was analyzed by flow cytometry. IL-17A was
      expressed by gammadelta-T cells and TCRbeta+ natural Th17 (nTh17) cells, as
      recently reported. Although infiltrating neutrophils were recruited to the tongue
      following infection, they did not express the IL-17A reporter. Moreover,
      neutrophil-depleted mice exhibited normal transcription of both Il17a and
      downstream IL-17-dependent gene targets after Candida challenge. Thus, in acute
      OPC, neutrophils are not a measurable source of IL-17 production, nor are they
      necessary to trigger IL-17-dependent gene expression, although they are essential
      for ultimate pathogen control. 

PMID- 26213976
TI  - Coordination of Candida albicans Invasion and Infection Functions by
      Phosphoglycerol Phosphatase Rhr2.
AB  - The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme,
      is required for biofilm formation in vitro and in vivo. Prior studies indicate
      that RHR2 is ultimately required for expression of adhesin genes, such as ALS1.
      In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed
      from an RHR2-independent promoter. Here, we describe two additional biological
      processes that depend upon RHR2: invasion into an abiotic substrate and
      pathogenicity in an abdominal infection model. We report here that abiotic
      substrate invasion occurs concomitantly with biofilm formation, and a screen of
      transcription factor mutants indicates that biofilm and hyphal formation ability
      correlates with invasion ability. However, analysis presented here of the
      rhr2Delta/Delta mutant separates biofilm formation and invasion. We found that an
      rhr2Delta/Delta mutant forms a biofilm upon overexpression of the adhesin gene
      ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming
      strains do not invade the substrate. These results indicate that RHR2 has an
      adhesin-independent role in substrate invasion, and mathematical modeling argues
      that RHR2 is required to generate turgor. Previous studies have shown that
      abdominal infection by C. albicans has two aspects: infection of abdominal organs
      and persistence in abscesses. We report here that an rhr2Delta/Delta mutant is
      defective in both of these infection phenotypes. We find here that overexpression
      of ALS1 in the mutant restores infection of organs, but does not improve
      persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in
      abdominal infection, just as it does in substrate invasion. This report suggests
      that RHR2, through glycerol synthesis, coordinates adherence with host- or
      substrate-interaction activities that enable proliferation of the C. albicans
      population. 

PMID- 26213977
TI  - Opportunistic Pathogens Mycobacterium Avium Complex (MAC) and Legionella spp.
      Colonise Model Shower.
AB  - Legionella spp. and Mycobacterium avium complex (MAC) are opportunistic pathogens
      of public health concern. Hot water systems, including showers, have been
      identified as a potential source of infection. This paper describes the
      colonization of Legionella and MAC on the flexible tubing within a model potable
      shower system, utilizing thermostatic mixing and a flexible shower head. A MAC
      qPCR method of enumeration was also developed. MAC and Legionella spp. were
      detected within the biofilm at maximum concentrations of 7.0 * 104 and 2.0 * 103
      copies/cm2 PVC tubing respectively. No significant changes were observed between
      sample of the flexible shower tubing that dried between uses and those that
      remained filled with water. This suggested the "unhooking" showerheads and
      allowing them to dry is not an effective method to reduce the risk of Legionella
      or MAC colonisation. 

PMID- 26213978
TI  - The Effect of Superstructures Connected to Implants with Different Surface
      Properties on the Surrounding Bone.
AB  - The objective of this study was to investigate how the connection of
      superstructures to implants with different surface properties affects the
      surrounding bone. The right and left mandibular premolars and molars of 5 dogs
      were extracted. After 12 weeks, a machined implant was placed mesially and an
      anodized implant was placed distally on one side of the edentulous jaw, with the
      positions reversed on the opposite side. Twelve weeks after implantation,
      splinted superstructures were set to the implants. At 24 weeks after
      implantation, the implant stability quotient (ISQ) was measured, radiographs were
      obtained. Removal torque values were measured and histologic observation was
      performed. The ISQ values at 24 weeks after implantation were not significantly
      different between the groups. The removal torque values were significantly
      different between the distal anodized and distal machined implants (p < 0.05).
      From 12 to 24 weeks, marginal bone losses were not significantly different
      between the groups. Fluorescent observation of tissue samples revealed bone
      remodeling activity around all of the implants. The results of this study suggest
      that when implants with different surface properties are connected, machined
      implants at the most distal sites might be a potential risk factor for implant
      bone binding. 

PMID- 26213979
TI  - SPR Biosensor Probing the Interactions between TIMP-3 and Heparin/GAGs.
AB  - Tissue inhibitor of metalloproteinases-3 (TIMP-3) belongs to a family of proteins
      that regulate the activity of matrix metalloproteinases (MMPs), which can process
      various bioactive molecules such as cell surface receptors, chemokines, and
      cytokines. Glycosaminoglycans (GAGs) interact with a number of proteins, thereby
      playing an essential role in the regulation of many physiological/patho
      physiological processes. Both GAGs and TIMP/MMPs play a major role in many cell
      biological processes, including cell proliferation, migration, differentiation,
      angiogenesis, apoptosis, and host defense. In this report, a heparin biosensor
      was used to map the interaction between TIMP-3 and heparin and other GAGs by
      surface plasmon resonance spectroscopy. These studies show that TIMP-3 is a
      heparin-binding protein with an affinity of ~59 nM. Competition surface plasmon
      resonance analysis indicates that the interaction between TIMP-3 and heparin is
      chain-length dependent, and N-sulfo and 6-O-sulfo groups (rather than the 2-O
      sulfo groups) in heparin are important in the interaction of heparin with TIMP-3.
      Other GAGs (including chondroitin sulfate (CS) type E (CS-E)and CS type B (CS
      B)demonstrated strong binding to TIMP-3, while heparan sulfate (HS), CS type A
      (CSA), CS type C (CSC), and CS type D (CSD) displayed only weak binding affinity.

PMID- 26213980
TI  - Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for
      Human Galectin-3.
AB  - Carbohydrate-lectin interactions are relatively weak. As they play an important
      role in biological recognition processes, multivalent glycan ligands are designed
      to enhance binding affinity and inhibitory potency. We here report on novel neo
      glycoproteins based on bovine serum albumin as scaffold for multivalent
      presentation of ligands for galectins. We prepared two kinds of tetrasaccharides
      (N-acetyllactosamine and N,N-diacetyllactosamine terminated) by multi-step chemo
      enzymatic synthesis utilizing recombinant glycosyltransferases. Subsequent
      conjugation of these glycans to lysine groups of bovine serum albumin via squaric
      acid diethyl ester yielded a set of 22 different neo-glycoproteins with tuned
      ligand density. The neo-glycoproteins were analyzed by biochemical and
      chromatographic methods proving various modification degrees. The neo
      glycoproteins were used for binding and inhibition studies with human galectin-3
      showing high affinity. Binding strength and inhibition potency are closely
      related to modification density and show binding enhancement by multivalent
      ligand presentation. At galectin-3 concentrations comparable to serum levels of
      cancer patients, we detect the highest avidities. Selectivity of N,N
      diacetyllactosamine terminated structures towards galectin-3 in comparison to
      galectin-1 is demonstrated. Moreover, we also see strong inhibitory potency of
      our scaffolds towards galectin-3 binding. These novel neo-glycoproteins may
      therefore serve as selective and strong galectin-3 ligands in cancer related
      biomedical research. 

PMID- 26213981
TI  - Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity.
AB  - alpha-Synuclein inclusion bodies are a pathological hallmark of several
      neurodegenerative diseases, including Parkinson's disease, and contain aggregated
      alpha-synuclein and a variety of recruited factors, including protein chaperones,
      proteasome components, ubiquitin and the small ubiquitin-like modifier, SUMO-1.
      Cell culture and animal model studies suggest that misfolded, aggregated alpha
      synuclein is actively translocated via the cytoskeletal system to a region of the
      cell where other factors that help to lessen the toxic effects can also be
      recruited. SUMO-1 covalently conjugates to various intracellular target proteins
      in a way analogous to ubiquitination to alter cellular distribution, function and
      metabolism and also plays an important role in a growing list of cellular
      pathways, including exosome secretion and apoptosis. Furthermore, SUMO-1 modified
      proteins have recently been linked to cell stress responses, such as oxidative
      stress response and heat shock response, with increased SUMOylation being
      neuroprotective in some cases. Several recent studies have linked SUMOylation to
      the ubiquitin-proteasome system, while other evidence implicates the lysosomal
      pathway. Other reports depict a direct mechanism whereby sumoylation reduced the
      aggregation tendency of alpha-synuclein, and reduced the toxicity. However, the
      precise role of SUMO-1 in neurodegeneration remains unclear. In this review, we
      explore the potential direct or indirect role(s) of SUMO-1 in the cellular
      response to misfolded alpha-synuclein in neurodegenerative disorders. 

PMID- 26213983
TI  - Physical Activity and Risk of Lung Cancer: A Meta-analysis.
AB  - OBJECTIVE: Previous studies concerning the association between physical activity
      (PA) and risk of lung cancer yielded mixed results. We investigated the
      association by performing a meta-analysis. DATA SOURCES: Relevant studies were
      identified by searching PubMed and EMBASE to January 2014. Twelve cohort studies
      and 6 case-control studies involving 2 468 470 participants and 26 453 cases of
      lung cancer were selected for meta-analysis. MAIN RESULTS: We calculated the
      summary relative risk (RR) and 95% confidence intervals (CIs) using random
      effects models. The analyses showed that individuals who participated in any
      amount of PA had an RR of 0.79 (95% CI, 0.73-0.86) for risk of lung cancer. Those
      who participated in high PA (vs low PA) had an RR of 0.75 (95% CI, 0.68-0.84).
      Stratifying by study design (case-control and cohort studies), smoking status
      (current, former, and never smokers), and gender, similar inverse associations
      were found for all the subgroups except for never smokers subgroup. CONCLUSIONS:
      Pooled results from observational studies support a protective effect of PA
      against lung cancer.

PMID- 26213982
TI  - Pre-mRNA Splicing in Plants: In Vivo Functions of RNA-Binding Proteins Implicated
      in the Splicing Process.
AB  - Alternative pre-messenger RNA splicing in higher plants emerges as an important
      layer of regulation upon exposure to exogenous and endogenous cues. Accordingly,
      mutants defective in RNA-binding proteins predicted to function in the splicing
      process show severe phenotypic alterations. Among those are developmental
      defects, impaired responses to pathogen threat or abiotic stress factors, and
      misregulation of the circadian timing system. A suite of splicing factors has
      been identified in the model plant Arabidopsis thaliana. Here we summarize recent
      insights on how defects in these splicing factors impair plant performance. 

PMID- 26213985
TI  - A Systematic Review and Meta-Analysis of Brief Versus Ultrabrief Right Unilateral
      Electroconvulsive Therapy for Depression.
AB  - OBJECTIVE: Electroconvulsive therapy (ECT) is an effective depression treatment,
      but it has potential cognitive side effects. Ultrabrief pulse (UBP) right
      unilateral (RUL) ECT is an increasingly used treatment option that can
      potentially combine efficacy with lesser cognitive side effects. However, current
      trials are underpowered or have conflicting results. A systematic review and meta
      analysis was conducted to evaluate the relative efficacy and cognitive effects of
      brief pulse (BP) and UBP RUL ECT. DATA SOURCES: MEDLINE, EMBASE, PsycINFO,
      CENTRAL, DARE, and the International Clinical Trials Registry Platform were
      searched with the search terms ECT, electroconvulsive therapy, electroconvulsive
      shock, electroconvulsive shock therapy, electrical stimulation, electroconvulsive
      combined with brief, ultra*, pulse, and trial in English, all fields including
      title, abstract, subject heading, and full text up to June 20, 2013, for studies
      comparing BP and UBP RUL ECT in depressed patients that reported formalized mood
      ratings for depression. STUDY SELECTION: Six studies met the inclusion criteria,
      comprising a total of 689 patients. DATA EXTRACTION: Efficacy, cognitive,
      response, and remission outcomes were extracted from each publication or obtained
      directly from authors. RESULTS: BP RUL ECT was significantly more efficacious in
      treating depression than UBP RUL ECT (standardized mean difference = 0.25; 95%
      CI, 0.08-0.41; P = .004) but showed significantly more cognitive side effects in
      all cognitive domains examined (global cognition, anterograde learning and
      recall, retrograde memory) (P < .01). The mean number of treatment sessions given
      was 8.7 for BP ECT and 9.6 for UBP ECT (P < .001). UBP had a lower remission rate
      (OR = 0.71; 95% CI, 0.51-0.99; P = .045), with a number needed to treat of 12.1.
      CONCLUSIONS: BP compared with UBP RUL ECT was slightly more efficacious in
      treating depression and required fewer treatment sessions, but led to greater
      cognitive side effects. The decision of whether to use BP or UBP RUL ECT should
      be made on an individual patient basis and should be based on a careful weighing
      of the relative priorities of efficacy versus minimization of cognitive
      impairment.

PMID- 26213984
TI  - A Man in His 40s With Headache, Lethargy, and Altered Mental Status.
AB  - A man in his 40s presented with 1 month of worsening confusion, fatigue, and
      headache. Results from laboratory analyses were notable for a complete white
      blood cell count of 17 000/MUL (31% blast cells), a platelet count of 76 000/MUL,
      and a hemoglobin level of 16.6 g/dL. Imaging studies revealed a large mixed
      attenuation subdural collection in the right frontal region with prominent mass
      effect. The patient underwent an emergency neurosurgical procedure. The
      differential diagnosis, pathologic findings, and diagnosis are discussed.

PMID- 26213986
TI  - The 'Ireland' one-pot alcohol oxidation coupling reactions: celebrating 30 years
      of diverse synthesis.
AB  - In 1985, Robert Ireland and co-worker were devising synthetic routes to polyether
      ionophore antibiotics and during this process several highly reactive aldehydes
      were encountered, which made their isolation and subsequent elaboration
      difficult. To circumvent this problem, the synthetic route commenced from the
      alcohol which was oxidized to the aldehyde and, to the crude mixture, was added
      the nucleophile. This procedure, dubbed the 'Ireland' oxidative process was found
      to be highly successful and adapted by many research groups the world over. As we
      celebrate 30 years since this landmark discovery, the following review will take
      a journey of the most innovative and wonderful applications of this process. 

PMID- 26213988
TI  - Biomechanics of the Median Nerve During Stretching as Assessed by
      Ultrasonography.
AB  - The objective of this observational cross-sectional study was to investigate the
      normal motion of the median nerve when stretched during a neurodynamic exercise.
      In recent years, ultrasonography has been increasingly accepted as an imaging
      technique for examining peripheral nerves in vivo, offering a reliable and
      noninvasive method for a precise evaluation of nerve movement. Transverse motion
      of the median nerve in the arm during a neurodynamic test was measured. A
      volunteer sample of 22 healthy subjects (11 women) participated in the study.
      Nerve displacement and deformation were assessed by dynamic ultrasonography.
      Excellent interobserver agreement was obtained, with kappa coefficient of .7-.8.
      Ultrasonography showed no lateral motion during wrist extension in 68% of nerves,
      while 73% moved dorsally, with statistically significant differences between
      sexes (ORlat = 6.3; 95% CI = 1.4-27.7 and ORdor = 8.3; 95% CI = 1.6-44.6). The
      cross-sectional area was significantly greater in men (3.6 mm2). Quantitative
      analysis revealed no other statistically significant differences. Our results
      provide evidence of substantial individual differences in median nerve transverse
      displacement in response to a neurodynamic exercise. 

PMID- 26213987
TI  - Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic
      Lupus Erythematosus.
AB  - OBJECTIVE: To validate clinical indices of lupus nephritis activity and damage
      when used in children against the criterion standard of kidney biopsy findings.
      METHODS: In 83 children requiring kidney biopsy, the Systemic Lupus Erythematosus
      Disease Activity Index renal domain (SLEDAI-R), British Isles Lupus Assessment
      Group index renal domain (BILAG-R), Systemic Lupus International Collaborating
      Clinics (SLICC) renal activity score (SLICC-RAS), and SLICC Damage Index renal
      domain (SDI-R) were measured. Fixed effects and logistic models were calculated
      to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS)
      class; low-to-moderate versus high lupus nephritis activity (National Institutes
      of Health [NIH] activity index [AI]) score: <=10 versus >10; tubulointerstitial
      activity index (TIAI) score: <=5 versus >5; or the absence versus presence of
      lupus nephritis chronicity (NIH chronicity index) score: 0 versus >=1. RESULTS:
      There were 10, 50, and 23 patients with ISN/RPS class I/II, III/IV, and V,
      respectively. Scores of the clinical indices did not differentiate among patients
      by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with
      lupus nephritis activity status defined by NIH-AI scores, while only the SLEDAI-R
      scores differed between lupus nephritis activity status based on TIAI scores. The
      sensitivity and specificity of the SDI-R to capture lupus nephritis chronicity
      was 23.5% and 91.7%, respectively. Despite being designed to measure lupus
      nephritis activity, SLICC-RAS and SLEDAI-R scores significantly differed with
      lupus nephritis chronicity status. CONCLUSION: Current clinical indices of lupus
      nephritis fail to discriminate ISN/RPS class in children. Despite its
      shortcomings, the SLEDAI-R appears best for measuring lupus nephritis activity in
      a clinical setting. The SDI-R is a poor correlate of lupus nephritis chronicity.

PMID- 26213989
TI  - Photodynamic Treatment of Tumor with Bacteria Expressing KillerRed.
AB  - Photodynamic therapy (PDT) is a cancer treatment modality in which a
      photosensitizing dye is administered and exposed to light to kill tumor cells via
      the production of reactive oxygen species (ROS). A fundamental obstacle for PDT
      is the low specificity for staining solid tumors with dyes. Recently, a tumor
      targeting system guided by anaerobic bacteria was proposed for tumor imaging and
      treatment. Here, we explore the feasibility of the genetically encoded
      photosensitizer KillerRed, which is expressed in Escherichia coli, to treat
      tumors. Using nitroblue tetrazolium (NBT), we detected a lengthy ROS diffusion
      from the bodies of KillerRed-expressing bacteria in vitro, which demonstrated the
      feasibility of using bacteria to eradicate cells in their surroundings. In nude
      mice, Escherichia coli (E. coli) expressing KillerRed (KR-E. coli) were
      subcutaneously injected into xenografts comprising CNE2 cells, a human
      nasopharyngeal carcinoma cell line, and HeLa cells, a human cervical carcinoma
      cell line. KR-E. coli seemed to proliferate rapidly in the tumors as observed
      under an imaging system. When the intensity of fluorescence increased and the
      fluorescent area became as large as the tumor one day after KR-E. coli injection,
      the KR-E. coli-bearing tumor was irradiated with an orange light (lambda = 540
      580 nm). In all cases, the tumors became necrotic the next day and were
      completely eliminated in a few days. No necrosis was observed after the
      irradiation of tumors injected with a vehicle solution or a vehicle carrying the
      E. coli without KillerRed. In successfully treated mice, no tumor recurrence was
      observed for more than two months. E. coli genetically engineered for KillerRed
      expression are highly promising for the diagnosis and treatment of tumors when
      the use of bacteria in patients is cleared for infection safety.

PMID- 26213990
TI  - Investigation of Fatigability during Repetitive Robot-Mediated Arm Training in
      People with Multiple Sclerosis.
AB  - BACKGROUND: People with multiple sclerosis (MS) are encouraged to engage in
      exercise programs but an increased experience of fatigue may impede sustained
      participation in training sessions. A high number of movements is, however,
      needed for obtaining optimal improvements after rehabilitation. METHODS: This
      cross-sectional study investigated whether people with MS show abnormal
      fatigability during a robot-mediated upper limb movement trial. Sixteen people
      with MS and sixteen healthy controls performed five times three minutes of
      repetitive shoulder anteflexion movements. Movement performance, maximal
      strength, subjective upper limb fatigue and surface electromyography (median
      frequency and root mean square of the amplitude of the electromyography (EMG)
      signal of the anterior deltoid) were recorded during or in-between these
      exercises. After fifteen minutes of rest, one extra movement bout was performed
      to investigate how rest influences performance. RESULTS: A fifteen minutes upper
      limb movement protocol increased the perceived upper limb fatigue and induced
      muscle fatigue, given a decline in maximal anteflexion strength and changes of
      both the amplitude and the median frequency of EMG the anterior deltoid. In
      contrast, performance during the 3 minutes of anteflexion movements did not
      decline. There was no relation between changes in subjective fatigue and the
      changes in the amplitude and the median frequency of the anterior deltoid muscle,
      however, there was a correlation between the changes in subjective fatigue and
      changes in strength in people with MS. People with MS with upper limb weakness
      report more fatigue due to the repetitive movements, than people with MS with
      normal upper limb strength, who are comparable to healthy controls. The weak
      group could, however, keep up performance during the 15 minutes of repetitive
      movements. DISCUSSION AND CONCLUSION: Albeit a protocol of repetitive shoulder
      anteflexion movements did not elicit a performance decline, fatigue feelings
      clearly increased in both healthy controls and people with MS, with the largest
      increase in people with MS with upper limb weakness. Objective fatigability was
      present in both groups with a decline in the muscle strength and increase of
      muscle fatigue, shown by changes in the EMG parameters. However, although weak
      people with multiple sclerosis experienced more fatigue, the objective signs of
      fatigability were less obvious in weak people with MS, perhaps because this
      subgroup has central limiting factors, which influence performance from the start
      of the movements.

PMID- 26213993
TI  - An ultrafast spectroscopic and quantum mechanical investigation of multiple
      emissions in push-pull pyridinium derivatives bearing different electron donors.
AB  - A joint experimental and theoretical approach, involving state-of-the-art
      femtosecond fluorescence up-conversion measurements and quantum mechanical
      computations including vibronic effects, was employed to get a deep insight into
      the excited state dynamics of two cationic dipolar chromophores (Donor-pi
      Acceptor(+)) where the electron deficient portion is a N-methyl pyridinium and
      the electron donor a trimethoxyphenyl or a pyrene, respectively. The ultrafast
      spectroscopic investigation, and the time resolved area normalised emission
      spectra in particular, revealed a peculiar multiple emissive behaviour and
      allowed the distinct emitting states to be remarkably distinguished from
      solvation dynamics, occurring in water in a similar timescale. The two and three
      emissions experimentally detected for the trimethoxyphenyl and pyrene
      derivatives, respectively, were associated with specific local emissive minima in
      the potential energy surface of S1 on the ground of quantum-mechanical
      calculations. A low polar and planar Locally Excited (LE) state together with a
      highly polar and Twisted Intramolecular Charge Transfer (TICT) state is
      identified to be responsible for the dual emission of the trimethoxyphenyl
      compound. Interestingly, the more complex photobehaviour of the pyrenyl
      derivative was explained considering the contribution to the fluorescence coming
      not only from the LE and TICT states but also from a nearly Planar Intramolecular
      Charge Transfer (PICT) state, with both the TICT and the PICT generated from LE
      by progressive torsion around the quasi-single bond between the methylpyridinium
      and the ethene bridge. These findings point to an interconversion between
      rotamers for the pyrene compound taking place in its excited state against the
      Non-equilibrated Excited Rotamers (NEER) principle. 

PMID- 26213991
TI  - Risk Factors for Development of Acute Kidney Injury in Patients with Urinary
      Tract Infection.
AB  - Acute kidney injury (AKI) is associated with high morbidity and mortality.
      Urinary tract infection (UTI) may be associated with sepsis or septic shock, and
      cause sudden deterioration of renal function. This study investigated the
      clinical characteristics and change of renal function to identify the risk
      factors for development of AKI in UTI patients. This retrospective study was
      conducted in a tertiary referral center. From January 2006 to January 2013, a
      total of 790 UTI patients necessitating hospital admission were included for
      final analysis. Their demographic and clinical characteristics and comorbidities
      were collected and compared. Multivariate logistic regression analysis was
      performed to evaluate the risk factors for AKI in UTI patients. There were 97
      (12.3%) patients developing AKI during hospitalization. Multivariate logistic
      regression analysis showed that patients with older age (OR 1.02, 95% CI 1.00
      1.04, P = 0.04), diabetes mellitus (DM) (OR 2.23, 95% CI 1.35-3.68, P = 0002),
      upper UTI (OR 2.63, 95% CI 1.53-4.56, P = 0001), afebrile during hospitalization
      (OR 1.71, 95% CI 1.04-2.83, P = 0036) and lower baseline eGFR [baseline eGFR 45
      59 mL/min/1.73 m2 (OR 2.12, 95% CI 1.12-4.04, P = 0.022), baseline eGFR 30-44
      mL/min/1.73 m2 (OR 4.44, 95% CI 2.30-8.60 P < 0.001) baseline eGFR < 30
      mL/min/1.73 m2 (OR 4.72, 95% CI 2.13-10.45, P <0.001), respectively] were
      associated with increased risk for development of AKI. were associated with
      increased risk for development of AKI. Physicians should pay attention to UTI
      patients at risk of AKI (advancing age, DM, upper UTI, afebrile, and impaired
      baseline renal function). 

PMID- 26213992
TI  - Identification of Cryptosporidium Species in Fish from Lake Geneva (Lac Leman) in
      France.
AB  - Cryptosporidium, a protozoan parasite that can cause severe diarrhea in a wide
      range of vertebrates including humans, is increasingly recognized as a parasite
      of a diverse range of wildlife species. However, little data are available
      regarding the identification of Cryptosporidium species and genotypes in wild
      aquatic environments, and more particularly in edible freshwater fish. To
      evaluate the prevalence of Cryptosporidiumspp. in fish from Lake Geneva (Lac
      Leman) in France, 41 entire fish and 100 fillets (cuts of fish flesh) were
      collected from fishery suppliers around the lake. Nested PCR using degenerate
      primers followed by sequence analysis was used. Five fish species were identified
      as potential hosts of Cryptosporidium: Salvelinus alpinus, Esox lucius, Coregonus
      lavaretus, Perca fluviatilis, and Rutilus rutilus. The presence of
      Cryptosporidium spp. was found in 15 out of 41 fish (37%), distributed as
      follows: 13 (87%) C. parvum, 1 (7%) C. molnari, and 1 (7%) mixed infection (C.
      parvum and C. molnari). C. molnari was identified in the stomach, while C. parvum
      was found in the stomach and intestine. C. molnari was also detected in 1 out of
      100 analyzed fillets. In order to identify Cryptosporidium subtypes, sequencing
      of the highly polymorphic 60-kDa glycoprotein (gp60) was performed. Among the C.
      parvum positive samples, three gp60 subtypes were identified: IIaA15G2R1,
      IIaA16G2R1, and IIaA17G2R1. Histological examination confirmed the presence of
      potential developmental stages of C. parvum within digestive epithelial cells.
      These observations suggest that C. parvum is infecting fish, rather than being
      passively carried. Since C. parvum is a zoonotic species, fish potentially
      contaminated by the same subtypes found in terrestrial mammals would be an
      additional source of infection for humans and animals, and may also contribute to
      the contamination of the environment with this parasite. Moreover, the risk of
      human transmission is strengthened by the observation of edible fillet
      contamination. 

PMID- 26213994
TI  - Purification and biochemical characterization of an alkaline protease from marine
      bacteria Pseudoalteromonas sp. 129-1.
AB  - An extracellular alkaline protease produced by marine bacteria strain
      Pseudoalteromonas sp. 129-1 was purified by ammonium sulphate precipitation,
      anion exchange chromatography, and gel filtration. The purity of the protease was
      confirmed by SDS-PAGE and molecular mass was estimated to be 35 kDa. The protease
      maintained considerable activity and stability at a wide temperature range of 10
      60  degrees C and pH range of 6-11, and optimum activity was detected at
      temperature of 50  degrees C and pH of 8. Metallo-protease inhibitor, EDTA, had
      no inhibitory effect on protease activity even at concentration up to 15 mM,
      whereas 15 mM PMSF, a common serine protease inhibitor, greatly inactivated the
      protease. The high stability of the protease in the presence of surfactants (SDS,
      Tween 80, and Triton X-100), oxidizing agent H(2)O(2), and commercial detergents
      was observed. Moreover, the protease was tolerant to most of the tested organic
      solvents, and saline tolerant up to 30%. Interestingly, biofilm of Pseudomonas
      aeruginosa PAO1 was greatly reduced by 0.01 mg ml(-1) of the protease, and nearly
      completely abolished with the concentration of 1 mg ml(-1). Collectively, the
      protease showed valuable feathers as an additive in laundry detergent and non
      toxic anti-biofilm agent.

PMID- 26213995
TI  - The properties of substituted 3D-aromatic neutral carboranes: the potential for
      sigma-hole bonding.
AB  - The calculated properties of substituted carboranes such as dipole moment,
      polarisability, the magnitude of the sigma-hole and the desolvation free energy
      are compared with these properties in comparable aromatic and cyclic aliphatic
      organic compounds. Dispersion and charge transfer energies are similar. However,
      the predicted strength of the halogen bonds with the same electron donor (based
      on the magnitude of the sigma-hole) is larger for neutral C-vertex halogen
      substituted carboranes than for their organic counterparts. Furthermore, the
      desolvation penalties of substituted carboranes are smaller than those of the
      corresponding organic compounds, which should further strengthen the halogen
      bonds of the former in the solvent. It is predicted that substituted carboranes
      have the potential to form stronger halogen bonds than comparable aromatic
      hydrocarbons, which will be even more pronounced in the medium. This theoretical
      study thus lays ground for the rational engineering of halogen bonding in
      inorganic crystals as well as in biomolecular complexes. 

PMID- 26213996
TI  - Let's Make Gender Diversity in Data Science a Priority Right from the Start.
AB  - The emergent field of data science is a critical driver for innovation in all
      sectors, a focus of tremendous workforce development, and an area of increasing
      importance within science, technology, engineering, and math (STEM). In all of
      its aspects, data science has the potential to narrow the gender gap and set a
      new bar for inclusion. To evolve data science in a way that promotes gender
      diversity, we must address two challenges: (1) how to increase the number of
      women acquiring skills and working in data science and (2) how to evolve
      organizations and professional cultures to better retain and advance women in
      data science. Everyone can contribute. 

PMID- 26213997
TI  - Differential expression of microRNA-206 and its target genes in preeclampsia.
AB  - OBJECTIVES: Preeclampsia is a multisystem disease that significantly contributes
      to maternal and foetal morbidity and mortality. In this study, we used a
      nonbiased microarray approach to identify novel circulating miRNAs in maternal
      plasma that may be associated with preeclampsia. METHODS: Plasma samples were
      obtained at 16 and 28 weeks of gestation from 18 women who later developed
      preeclampsia (cases) and 18 matched women with normotensive pregnancies
      (controls). We studied miRNA expression profiles in plasma and subsequently
      confirmed miRNA and target gene expression in placenta samples. Placental samples
      were obtained from an independent cohort of 19 women with preeclampsia matched
      with 19 women with normotensive pregnancies. RESULTS: From the microarray, we
      identified one miRNA that was significantly differentially expressed between
      cases and controls at 16 weeks of gestation and six miRNAs that were
      significantly differentially expressed at 28 weeks. Following qPCR validation,
      only one miR-206 was found to be significantly increased in 28-week samples in
      women who later developed preeclampsia (1.4-fold change +/- 0.2). The trend for
      increase in miR-206 expression was mirrored within placental tissue from women
      with preeclampsia. In parallel, IGF-1, a target gene of miR-206, was also found
      to be downregulated (0.41 +/- 0.04) in placental tissue from women with
      preeclampsia. miR-206 expression was also detectable in myometrium tissue and
      trophoblast cell lines. CONCLUSION: Our pilot study has identified miRNA-206 as a
      novel factor upregulated in preeclampsia within the maternal circulation and in
      placental tissue.

PMID- 26213998
TI  - Electron beam induced evolution in Au, Ag, and interfaced heterogeneous Au/Ag
      nanoparticles.
AB  - A sintering process of nanoparticles made of Ag, Au, and interfaced Ag/Au
      heterodimers was investigated by in situ transmission electron microscopy at room
      temperature. Such a process is driven by the illumination of a high-energy
      electron beam accelerated at 200 kV that promotes atom diffusion in the
      nanoparticles that are in physical contact. Upon electron illumination, adjacent
      Au nanoparticles gradually merge together to form a larger particle along with
      the reduction of the surface area despite the fact that orientated attachment is
      not observed. According to the detailed analysis of the size change of the
      particles and the contact area, it was found that the nanoparticle fusion process
      is significantly different from the well-established thermal diffusion mechanism.
      In addition to the similar fusion process of Au nanoparticles, Ag nanoparticles
      undergo apparent sublimation induced by knock on damage because the transferred
      energy from the electron beam to nanoparticles is higher than the surface binding
      energy of Ag atoms when the electron scattering angle is larger than 112 degrees
      . The particles with a smaller size diffuse faster. Surface diffusion dominates
      at the beginning of the fusion process followed by slower lattice diffusion.
      Electron beam illumination can transform the interfaced Au/Ag dimers to Au@Ag
      core-shell particles followed by a slow removal of the Ag shells. This process
      under normal electron beam illumination is a lot faster than the thermally driven
      process. Both diffusion and sublimation of Ag atoms are dependent on the
      intensity of the electron beam, i.e., a higher beam intensity is favorable to
      accelerate both the processes. 

PMID- 26214000
TI  - Discovery and Structure Determination of an Unusual Sulfide Telluride through an
      Effective Combination of TEM and Synchrotron Microdiffraction.
AB  - The structure elucidation of the novel sulfide telluride Pb8Sb8S15Te5
      demonstrates a new versatile procedure that exploits the synergism of electron
      microscopy and synchrotron diffraction methods for accurate structure analyses of
      side-phases in heterogeneous microcrystalline samples. Suitable crystallites of
      unknown compounds can be identified by transmission electron microscopy and
      relocated and centered in a microfocused synchrotron beam by means of X-ray
      fluorescence scans. The refined structure model is then confirmed by simulating
      HRTEM images of the same crystallite. Pb8Sb8S15Te5 consists of chains of
      heterocubane-like units. Cation coordination polyhedra form unusually entwined
      chains of edge- and face-sharing bicapped trigonal prisms. The structure data are
      precise enough for bond-valence calculations, which confirm the disordered atom
      distribution. On this basis, optimization of physical properties becomes
      feasible.

PMID- 26214001
TI  - An Optimization Model for the Selection of Bus-Only Lanes in a City.
AB  - The planning of urban bus-only lane networks is an important measure to improve
      bus service and bus priority. To determine the effective arrangement of bus-only
      lanes, a bi-level programming model for urban bus lane layout is developed in
      this study that considers accessibility and budget constraints. The goal of the
      upper-level model is to minimize the total travel time, and the lower-level model
      is a capacity-constrained traffic assignment model that describes the passenger
      flow assignment on bus lines, in which the priority sequence of the transfer
      times is reflected in the passengers' route-choice behaviors. Using the proposed
      bi-level programming model, optimal bus lines are selected from a set of
      candidate bus lines; thus, the corresponding bus lane network on which the
      selected bus lines run is determined. The solution method using a genetic
      algorithm in the bi-level programming model is developed, and two numerical
      examples are investigated to demonstrate the efficacy of the proposed model. 

PMID- 26213999
TI  - Evolutionary Analyses and Natural Selection of Betaine-Homocysteine S
      Methyltransferase (BHMT) and BHMT2 Genes.
AB  - Betaine-homocysteine S-methyltransferase (BHMT) and BHMT2 convert homocysteine to
      methionine using betaine and S-methylmethionine, respectively, as methyl donor
      substrates. Increased levels of homocysteine in blood are associated with
      cardiovascular disease. Given their role in human health and nutrition, we
      identified BHMT and BHMT2 genes and proteins from 38 species of deuterostomes
      including human and non-human primates. We aligned the genes to look for
      signatures of selection, to infer evolutionary rates and events across lineages,
      and to identify the evolutionary timing of a gene duplication event that gave
      rise to two genes, BHMT and BHMT2. We found that BHMT was present in the genomes
      of the sea urchin, amphibians, reptiles, birds and mammals; BHMT2 was present
      only across mammals. BHMT and BHMT2 were present in tandem in the genomes of all
      monotreme, marsupial and placental species examined. Evolutionary rates were
      accelerated for BHMT2 relative to BHMT. Selective pressure varied across
      lineages, with the highest dN/dS ratios for BHMT and BHMT2 occurring immediately
      following the gene duplication event, as determined using GA Branch analysis.
      Nine codons were found to display signatures suggestive of positive selection;
      these contribute to the enzymatic or oligomerization domains, suggesting
      involvement in enzyme function. Gene duplication likely occurred after the
      divergence of mammals from other vertebrates but prior to the divergence of
      extant mammalian subclasses, followed by two deletions in BHMT2 that affect
      oligomerization and methyl donor specificity. The faster evolutionary rate of
      BHMT2 overall suggests that selective constraints were reduced relative to BHMT.
      The dN/dS ratios in both BHMT and BHMT2 was highest following the gene
      duplication, suggesting that purifying selection played a lesser role as the two
      paralogs diverged in function. 

PMID- 26214002
TI  - Distributional Learning of Lexical Tones: A Comparison of Attended vs. Unattended
      Listening.
AB  - This study examines whether non-tone language listeners can acquire lexical tone
      categories distributionally and whether attention in the training phase modulates
      the effect of distributional learning. Native Australian English listeners were
      trained on a Thai lexical tone minimal pair and their performance was assessed
      using a discrimination task before and after training. During Training,
      participants either heard a Unimodal distribution that would induce a single
      central category, which should hinder their discrimination of that minimal pair,
      or a Bimodal distribution that would induce two separate categories that should
      facilitate their discrimination. The participants either heard the distribution
      passively (Experiments 1A and 1B) or performed a cover task during training
      designed to encourage auditory attention to the entire distribution (Experiment
      2). In passive listening (Experiments 1A and 1B), results indicated no effect of
      distributional learning: the Bimodal group did not outperform the Unimodal group
      in discriminating the Thai tone minimal pairs. Moreover, both Unimodal and
      Bimodal groups improved above chance on most test aspects from Pretest to
      Posttest. However, when participants' auditory attention was encouraged using the
      cover task (Experiment 2), distributional learning was found: the Bimodal group
      outperformed the Unimodal group on a novel test syllable minimal pair at Posttest
      relative to at Pretest. Furthermore, the Bimodal group showed above-chance
      improvement from Pretest to Posttest on three test aspects, while the Unimodal
      group only showed above-chance improvement on one test aspect. These results
      suggest that non-tone language listeners are able to learn lexical tones
      distributionally but only when auditory attention is encouraged in the
      acquisition phase. This implies that distributional learning of lexical tones is
      more readily induced when participants attend carefully during training,
      presumably because they are better able to compute the relevant statistics of the
      distribution. 

PMID- 26214003
TI  - Does Hooke's law work in helical nanosprings?
AB  - Hooke's law is a principle of physics that states that the force needed to extend
      a spring by some distance is proportional to that distance. The law is always
      valid for an initial portion of the elastic range for nearly all helical
      macrosprings. Here we report the sharp nonlinear force-displacement relation of
      tightly wound helical carbon nanotubes at even small displacement via a molecular
      mechanics model. We demonstrate that the van der Waals (vdW) interaction between
      the intertube walls dominates the nonlinear relation based on our analytical
      expressions. This study provides physical insights into the origin of huge
      nonlinearity of the helical nanosprings. 

PMID- 26214004
TI  - Improving Manufacturer Reporting of Adverse Events to the US Food and Drug
      Administration.

PMID- 26214006
TI  - Reactivity of a pyridinium-substituted dimethyldihydropyrene switch under aerobic
      conditions: self-sensitized photo-oxygenation and thermal release of singlet
      oxygen.
AB  - The behavior of a pyridinium-substituted dimethyldihydropyrene photo-switch under
      aerobic conditions was investigated. During irradiation with red light (lambda >=
      630 nm), this compound plays the role of oxygen sensitizer and is quantitatively
      converted into an endoperoxide derivative. The photo-produced endoperoxide then
      thermally releases singlet oxygen to regenerate the starting compound. 

PMID- 26214007
TI  - Early bronchus-associated lymphoid tissue lymphoma diagnosed using immunoglobulin
      heavy chain molecular testing.

PMID- 26214005
TI  - Different Stability and Proteasome-Mediated Degradation Rate of SMN Protein
      Isoforms.
AB  - The key pathogenic steps leading to spinal muscular atrophy (SMA), a genetic
      disease characterized by selective motor neuron degeneration, are not fully
      clarified. The full-length SMN protein (FL-SMN), the main protein product of the
      disease gene SMN1, plays an established role in the cytoplasm in snRNP biogenesis
      ultimately leading to mRNA splicing within the nucleus. It is also involved in
      the mRNA axonal transport. However, to what extent the impairment of these two
      SMN functions contributes to SMA pathogenesis remains unknown. A shorter SMN
      isoform, axonal-SMN or a-SMN, with more specific axonal localization, has been
      discovered, but whether it might act in concert with FL-SMN in SMA pathogenesis
      is not known. As a first step in defining common or divergent intracellular roles
      of FL-SMN vs a-SMN proteins, we here characterized the turn-over of both proteins
      and investigated which pathway contributed to a-SMN degradation. We performed
      real time western blot and confocal immunofluorescence analysis in easily
      controllable in vitro settings. We analyzed co-transfected NSC34 and HeLa cells
      and cell clones stably expressing both a-SMN and FL-SMN proteins after specific
      blocking of transcript or protein synthesis and inhibition of known intracellular
      degradation pathways. Our data indicated that whereas the stability of both FL
      SMN and a-SMN transcripts was comparable, the a-SMN protein was characterized by
      a much shorter half-life than FL-SMN. In addition, as already demonstrated for FL
      SMN, the Ub/proteasome pathway played a major role in the a-SMN protein
      degradation. We hypothesize that the faster degradation rate of a-SMN vs FL-SMN
      is related to the protection provided by the protein complex in which FL-SMN is
      assembled. The diverse a-SMN vs FL-SMN C-terminus may dictate different protein
      interactions and complex formation explaining the different localization and role
      in the neuronal compartment, and the lower expression and stability of a-SMN. 

PMID- 26214008
TI  - Challenges in developing primary care physicians' motivational interviewing
      skills.
AB  - INTRODUCTION: Motivational interviewing (MI) skills are relevant for primary care
      providers (PCPs) who are responsible for caring for patients with diseases
      affected by behavior. There are significant challenges associated with developing
      PCP's MI skills. We report on an effort to document the acquisition of MI skills
      by PCPs using an objective measure of MI competence, the Motivational
      Interviewing Treatment Integrity (MITI) coding system. METHOD: Eleven PCPs
      volunteered to participate in 6 MI workshops over a period of 6 months and to
      submit work samples between each of these workshops to be assessed with the MITI
      coding system. RESULTS: Thirteen of the expected 55 work samples were submitted
      before the final workshop. A revised approach was implemented in which each
      participant completed 2 simulated patient encounters. None of the providers
      reached the MITI's Beginning Proficiency threshold of MI skill. DISCUSSION: Six
      MI workshops were not sufficient to help motivated PCPs achieve Beginning
      Proficiency as measured by the MITI. Participants failed to submit most of the
      work samples for feedback on their MI practice, which may have contributed to
      their limited acquisition of MI skills. Helping PCPs develop MI skills likely
      requires more than participation in a series of workshops totaling 18 h.
      Questions remain about the feasibility of training PCPs to be competent in MI.
      Approaches such as use of simulated patients, peer observation, or specific
      protected time for obtaining work samples may be required. (PsycINFO Database
      Record

PMID- 26214010
TI  - Towards a scale-bridging description of ferrogels and magnetic elastomers.
AB  - Ferrogels and magnetic elastomers differentiate themselves from other materials
      by their unique capability of reversibly changing shape and mechanical properties
      under the influence of an external magnetic field. A crucial issue in the study
      of these outstanding materials is the interaction between the mesoscopic magnetic
      particles and the polymer matrix in which they are embedded. Here we analyze
      interactions between two such particles connected by a polymer chain, a situation
      representative for particle-crosslinked magnetic gels. To make a first step
      towards a scale-bridging description of the materials, effective pair potentials
      for mesoscopic configurational changes are specified using microscopic input
      obtained from simulations. Furthermore, the impact of the presence of magnetic
      interactions on the probability distributions and thermodynamic quantities of the
      system is considered. The resulting mesoscopic model pair potentials can be used
      to economically model the system on the particle length scales. This first coarse
      graining step is important to realize simplified but realistic scale-bridging
      models for these promising materials. 

PMID- 26214009
TI  - Location of care for patients with borderline personality disorder: Challenges
      and opportunities in finding a home.
AB  - Patients with borderline personality disorder (BPD) represent a population with
      increased care needs and high provider demand, even in the best cases of quality
      integrated primary care. The current article outlines the complexities of working
      with patients with BPD in primary care, including when the transition to the
      specialty mental health sector may be warranted. Core factors around transitions
      of care (between integrated primary care and the specialty mental health sector)
      have been identified. These factors included suicidal ideations, psychiatric
      hospitalizations/conditions, physician consultation availability, behavioral
      provider availability, supervision availability, finances, and patient
      preferences. (PsycINFO Database Record 

PMID- 26214012
TI  - "Positive and negative item wording and its influence on the Assessment of
      Callous-Unemotional Traits": Correction to Ray et al. (2015).

PMID- 26214013
TI  - Scenes for Social Information Processing in Adolescence: Item and factor analytic
      procedures for psychometric appraisal.
AB  - Relatively little is known about measures used to investigate the validity and
      applications of social information processing theory. The Scenes for Social
      Information Processing in Adolescence includes items built using a participatory
      approach to evaluate the attribution of intent, emotion intensity, response
      evaluation, and response decision steps of social information processing. We
      evaluated a sample of 802 Portuguese adolescents (61.5% female; mean age = 16.44
      years old) using this instrument. Item analysis and exploratory and confirmatory
      factor analytic procedures were used for psychometric examination. Two measures
      for attribution of intent were produced, including hostile and neutral; along
      with 3 emotion measures, focused on negative emotional states; 8 response
      evaluation measures; and 4 response decision measures, including prosocial and
      impaired social behavior. All of these measures achieved good internal
      consistency values and fit indicators. Boys seemed to favor and choose overt and
      relational aggression behaviors more often; girls conveyed higher levels of
      neutral attribution, sadness, and assertiveness and passiveness. The Scenes for
      Social Information Processing in Adolescence achieved adequate psychometric
      results and seems a valuable alternative for evaluating social information
      processing, even if it is essential to continue investigation into its internal
      and external validity.

PMID- 26214011
TI  - Formation of Chlorination Byproducts and Their Emission Pathways in Chlorine
      Mediated Electro-Oxidation of Urine on Active and Nonactive Type Anodes.
AB  - Chlorination byproducts (CBPs) are harmful to human health and the environment.
      Their formation in chlorine mediated electro-oxidation is a concern for
      electrochemical urine treatment. We investigated the formation of chlorate,
      perchlorate, and organic chlorination byproducts (OCBPs) during galvanostatic
      (10, 15, 20 mA . cm(-2)) electro-oxidation of urine on boron-doped diamond (BDD)
      and thermally decomposed iridium oxide film (TDIROF) anodes. In the beginning of
      the batch experiments, the production of perchlorate was prevented by competing
      active chlorine and chlorate formation as well as by direct oxidation of organic
      substances. Perchlorate was only formed at higher specific charges (>17 Ah . L(
      1) on BDD and >29 Ah . L(-1) on TDIROF) resulting in chlorate and perchlorate
      being the dominant CBPs (>90% of initial chloride). BDD produced mainly short
      chained OCBPs (dichloromethane, trichloromethane, and tetrachloromethane),
      whereas longer chained OCBPs (1,2-dichloropropane and 1,2-dichloroethane) were
      more frequently found on TDIROF. The OCBPs were primarily eliminated by
      electrochemical stripping: On BDD, this pathway accounted for 40%
      (dichloromethane) to 100% (tetrachloromethane) and on TDIROF for 90% (1,2
      dichloroethane) to 100% (trichloromethane) of what was produced. A post-treatment
      of the liquid as well as the gas phase should be foreseen if CBP formation cannot
      be prevented by eliminating chloride or organic substances in a pretreatment.

PMID- 26214014
TI  - The performance of the K6 scale in a large school sample: A follow-up study
      evaluating measurement invariance on the Idaho Youth Prevention Survey.
AB  - Since 2013, Idaho has been building capacity and infrastructure through the
      Strategic Prevention Framework State Incentive Grant to prevent substance abuse
      and related problems, namely psychiatric morbidity. As this federal initiative
      requires states to engage in data-driven strategic planning at the state and
      community levels, clinically validated instruments are particularly valuable in
      the context of school surveys that have limited space and require timely
      administration. Thus, the K6 scale was included on the 2014 Idaho Youth
      Prevention Survey as a measure of nonspecific psychological distress. To verify
      the unidimensional structure of the K6, principal axis and confirmatory factor
      analyses were performed in a school-based sample of Idaho students (n = 12,150).
      A series of multigroup confirmatory factor analyses were then performed to
      evaluate measurement invariance across gender, age, and race. Overall, the
      prevalence of serious psychological distress in the past 30 days was 17.2% in
      Idaho. Factor analyses confirmed the 1-factor solution of the K6. Four levels of
      measurement invariance were demonstrated across gender, age, and race. Together,
      these results further illustrate the construct validity of the K6 for use in
      adolescent populations. Other states are encouraged to include the K6 on their
      school surveys to facilitate policy planning and resource allocation as well as
      generate cross-state comparisons. (PsycINFO Database Record

PMID- 26214015
TI  - The Chinese version of the 8-item Committed Action Questionnaire (ChCAQ-8): A
      preliminary analysis of the factorial and criterion validity.
AB  - Committed action is a key component of the psychological flexibility model that
      recently has been applied in chronic pain settings. Developed within the Western
      context, the 8-item Committed Action Questionnaire (CAQ-8) demonstrated good
      psychometric properties. This study aimed to translate the original English
      version of the CAQ-8 into Chinese (ChCAQ-8) and to assess its reliability, factor
      structure and concurrent criterion validity. A total of 210 Chinese patients with
      chronic pain completed the ChCAQ-8, the Chronic Pain Grade, the Pain
      Catastrophizing Scale, and the depression subscale of the Hospital Anxiety and
      Depression Scale. Results of confirmatory factor analysis showed both the 2
      factor correlated (CFI = .99) and hierarchical (CFI = .98) models met the minimum
      acceptable fit criterion. The 2 subscales and the entire scale of ChCAQ-8
      demonstrated good internal consistency (Cronbach's alphas ranging .70-.86). The
      ChCAQ-8 negative subscale score was significantly correlated with pain intensity,
      disability, pain catastrophizing, and depression in the expected direction. The
      ChCAQ-8 positive subscale was significantly correlated with pain castastrophizing
      and depression. Results of multivariate regression modeling showed the ChCAQ-8
      negative subscale predicted depression (std beta = .19, p < .01) and disability
      (std beta = .14, p < .05), after adjusting for pain intensity, pain duration and
      pain catastrophizing. Our findings offer preliminary data for the reliability,
      factorial and concurrent criterion validity of the ChCAQ-8 in the Chinese
      population. (PsycINFO Database Record

PMID- 26214016
TI  - A cognitive psychometric model for the psychodiagnostic assessment of memory
      related deficits.
AB  - Clinical tests used for psychodiagnostic purposes, such as the well-known
      Alzheimer's Disease Assessment Scale: Cognitive subscale (ADAS-Cog), include a
      free-recall task. The free-recall task taps into latent cognitive processes
      associated with learning and memory components of human cognition, any of which
      might be impaired with the progression of Alzheimer's disease (AD). A Hidden
      Markov model of free recall is developed to measure latent cognitive processes
      used during the free-recall task. In return, these cognitive measurements give us
      insight into the degree to which normal cognitive functions are differentially
      impaired by medical conditions, such as AD and related disorders. The model is
      used to analyze the free-recall data obtained from healthy elderly participants,
      participants diagnosed as having mild cognitive impairment, and participants
      diagnosed with early AD. The model is specified hierarchically to handle item
      differences because of the serial position curve in free recall, as well as
      within-group individual differences in participants' recall abilities. Bayesian
      hierarchical inference is used to estimate the model. The model analysis suggests
      that the impaired patients have the following: (1) long-term memory encoding
      deficits, (2) short-term memory (STM) retrieval deficits for all but very short
      time intervals, (3) poorer transfer into long-term memory for items successfully
      retrieved from STM, and (4) poorer retention of items encoded into long-term
      memory after longer delays. Yet, impaired patients appear to have no deficit in
      immediate recall of encoded words in long-term memory or for very short time
      intervals in STM.

PMID- 26214019
TI  - Ferroelectricity in molecular solids: a review of electrodynamic properties.
AB  - In conventional ferroelectrics the polarization is induced either by the relative
      displacement of positive and negative ions due to a lattice distortion or by the
      collective alignment of permanent electric dipoles. Strongly correlated materials
      with the inversion-symmetry-broken ground states feature electronic
      ferroelectricity, a phenomenon which has recently caught the attention of
      condensed matter physicists due to its great fundamental and technological
      importance. The discovery of electronic ferroelectricity in one and two
      dimensional molecular solids is an exciting development because they show a rich
      variety of nonlinear properties and complex electrodynamics, including nontrivial
      emergent excitations. We summarize key experimental results, sketch the current
      theoretical understanding and outline promising prospects of this phenomenon
      which have great potential for future electronic devices. 

PMID- 26214017
TI  - Isotope-edited FTIR reveals distinct aggregation and structural behaviors of
      unmodified and pyroglutamylated amyloid beta peptides.
AB  - Amyloid beta peptide (Abeta) is causatively associated with Alzheimer's disease
      (AD), and N-terminally truncated and pyroglutamylated Abeta peptides (AbetapE)
      exert hypertoxic effect by an unknown mechanism. Recent evidence has identified
      the prefibrillar oligomers of Abeta, not the fibrils, as the prevalent cytotoxic
      species. Structural characterization of Abeta and AbetapE oligomers is therefore
      important for better understanding of their toxic effect. Here we have used
      isotope-edited Fourier transform infrared (FTIR) spectroscopy to identify the
      conformational changes in Abeta(1-42) and AbetapE(3-42) upon aggregation,
      individually and in 1 : 1 molar combination. During the first two hours of
      exposure to aqueous buffer, the peptides undergo transition from mostly alpha
      helical to mostly beta-sheet structure. Data on peptides (13)C,(15)N-labeled at
      K(16)L(17)V(18) or V(36)G(37)G(38)V(39) allowed construction of structural models
      for the monomer and early oligomers. The peptide monomer comprises a beta-hairpin
      that involves residues upstream of the K(16)L(17)V(18) sequence and an N-terminal
      alpha-helix. The oligomers form by non-H-bonding interactions between the beta
      strands of neighboring beta-hairpins, in lateral or staggered manner, with the
      strands running parallel or antiparallel. Relative alpha-helical and beta-sheet
      propensities of Abeta(1-42) and AbetapE(3-42) depend on the ionic strength of the
      buffer, emphasizing the importance of ionic interactions in Abeta peptide
      structure and aggregation. It is inferred that N-terminal modification of
      AbetapE(3-42) affects the helix stability and thereby modulates beta-sheet
      oligomer formation. The data thus provide new insight into the molecular
      mechanism of Abeta oligomerization by emphasizing the role of the N-terminal
      transient alpha-helical structure and by identifying structural constraints for
      molecular organization of the oligomers.

PMID- 26214020
TI  - A Photobasic Functional Group.
AB  - Controlling chemical reactivity using light is a longstanding practice within
      organic chemistry, yet little has been done to modulate the basicity of
      compounds. Reported herein is a triazabutadiene that is rendered basic upon
      photoisomerization. The pH of an aqueous solution containing the water-soluble
      triazabutadiene can be adjusted with 350 nm light. Upon synthesizing a
      triazabutadiene that is soluble in aprotic organic solvents, we noted a similar
      light-induced change in basicity. As a proof of concept we took this photobase
      and used it to catalyze a condensation reaction. 

PMID- 26214018
TI  - The MIA pathway: a key regulator of mitochondrial oxidative protein folding and
      biogenesis.
AB  - Mitochondria are fundamental intracellular organelles with key roles in important
      cellular processes like energy production, Fe/S cluster biogenesis, and
      homeostasis of lipids and inorganic ions. Mitochondrial dysfunction is
      consequently linked to many human pathologies (cancer, diabetes,
      neurodegeneration, stroke) and apoptosis. Mitochondrial biogenesis relies on
      protein import as most mitochondrial proteins (about 10-15% of the human
      proteome) are imported after their synthesis in the cytosol. Over the last
      several years many mitochondrial translocation pathways have been discovered.
      Among them, the import pathway that targets proteins to the intermembrane space
      (IMS) stands out as it is the only one that couples import to folding and
      oxidation and results in the covalent modification of the incoming precursor that
      adopt internal disulfide bonds in the process (the MIA pathway). The discovery of
      this pathway represented a significant paradigm shift as it challenged the
      prevailing dogma that the endoplasmic reticulum is the only compartment of
      eukaryotic cells where oxidative folding can occur. The concept of the oxidative
      folding pathway was first proposed on the basis of folding and import data for
      the small Tim proteins that have conserved cysteine motifs and must adopt
      intramolecular disulfides after import so that they are retained in the
      organelle. The introduction of disulfides in the IMS is catalyzed by Mia40 that
      functions as a chaperone inducing their folding. The sulfhydryl oxidase Erv1
      generates the disulfide pairs de novo using either molecular oxygen or,
      cytochrome c and other proteins as terminal electron acceptors that eventually
      link this folding process to respiration. The solution NMR structure of Mia40
      (and supporting biochemical experiments) showed that Mia40 is a novel type of
      disulfide donor whose recognition capacity for its substrates relies on a
      hydrophobic binding cleft found adjacent to a thiol active CPC motif. Targeting
      of the substrates to this pathway is guided by a novel type of IMS targeting
      signal called ITS or MISS. This consists of only 9 amino acids, found upstream or
      downstream of a unique Cys that is primed for docking to Mia40 when the substrate
      is accommodated in the Mia40 binding cleft. Different routes exist to complete
      the folding of the substrates and their final maturation in the IMS.
      Identification of new Mia40 substrates (some even without the requirement of
      their cysteines) reveals an expanded chaperone-like activity of this protein in
      the IMS. New evidence on the targeting of redox active proteins like thioredoxin,
      glutaredoxin, and peroxiredoxin into the IMS suggests the presence of redox
      dependent regulatory mechanisms of the protein folding and import process in
      mitochondria. Maintenance of redox balance in mitochondria is crucial for normal
      cell physiology and depends on the cross-talk between the various redox signaling
      processes and the mitochondrial oxidative folding pathway. 

PMID- 26214022
TI  - Ennio De Renzi (1924-2014). A loving remembrance.

PMID- 26214021
TI  - 5-hydroxytryptamine receptor (5-HT1DR) promotes colorectal cancer metastasis by
      regulating Axin1/beta-catenin/MMP-7 signaling pathway.
AB  - Overexpression of 5-hydroxytryptamine (5-HT) in human cancer contributes to tumor
      metastasis, but the role of 5-HT receptor family in cancer has not been
      thoroughly explored. Here, we report overexpression of 5-HT(1D) receptor (5
      HT(1D)R) was associated with Wnt signaling pathway and advanced tumor stage. The
      underlying mechanism of 5-HT(1D)R-promoted tumor invasion was through its
      activation on the Axin1/beta-catenin/MMP-7 pathway. In an orthotopic colorectal
      cancer mouse model, we demonstrated that a 5-HT(1D)R antagonist (GR127935)
      effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in
      intestinal epithelium cells, we observed that 5-HT(1D)R played an important role
      in cell invasion via Axin1/beta-catenin/MMP-7 pathway. Together, our findings
      reveal an essential role of the physiologic level of 5-HT(1D)R in pulmonary
      metastasis of colorectal cancer.

PMID- 26214023
TI  - Integration of multimodal neuroimaging methods: a rationale for clinical
      applications of simultaneous EEG-fMRI.
AB  - Functional magnetic resonance imaging (fMRI), which has high spatial resolution,
      is increasingly used to evaluate cerebral functions in neurological and
      psychiatric diseases. The main limitation of fMRI is that it detects neural
      activity indirectly, through the associated slow hemodynamic variations. Because
      neurovascular coupling can be regionally altered by pathological conditions or
      drugs, fMRI responses may not truly reflect neural activity.
      Electroencephalography (EEG) recordings, which directly detect neural activity
      with optimal temporal resolution, can now be obtained during fMRI data
      acquisition. Therefore, there is a growing interest in combining the techniques
      to obtain simultaneous EEG-fMRI recordings. The EEG-fMRI approach has several
      promising clinical applications. The first is the detection of cortical areas
      involved in interictal and ictal epileptic activity. Second, combining evoked
      potentials with fMRI could be an accurate way to study eloquent cortical areas
      for the planning of neurosurgery or rehabilitation, circumventing the above
      mentioned limitation of fMRI. Finally, the use of this approach to evaluate the
      functional connectivity of resting-state networks would extend the applications
      of EEG-fMRI to uncooperative or unconscious patients. Integration of multimodal
      neuroimaging methods: a rationale for clinical applications of simultaneous EEG
      fMRI. 

PMID- 26214024
TI  - How genetics affects the brain to produce higher-level dysfunctions in myotonic
      dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is a multisystemic disorder dominated by muscular
      impairment and brain dysfunctions. Although brain damage has previously been
      demonstrated in DM1, its associations with the genetics and
      clinical/neuropsychological features of the disease are controversial. This study
      assessed the differential role of gray matter (GM) and white matter (WM) damage
      in determining higher-level dysfunctions in DM1. Ten patients with genetically
      confirmed DM1 and 16 healthy How genetics affects the brain to produce higher
      level dysfunctions in myotonic dystrophy type 1 matched controls entered the
      study. The patients underwent a neuropsychological assessment and quantification
      of CTG triplet expansion. All the subjects underwent MR scanning at 3T, with
      studies including T1-weighted volumes and diffusion-weighted images. Voxel-based
      morphometry and tractbased spatial statistics were used for unbiased
      quantification of regional GM atrophy and WM integrity. The DM1 patients showed
      widespread involvement of both tissues. The extent of the damage correlated with
      CTG triplet expansion and cognition. This study supports the idea that genetic
      abnormalities in DM1mainly target the WM, but GM involvement is also crucial in
      determining the clinical characteristics of DM1.

PMID- 26214025
TI  - Impact of C24:0 on actin-microtubule interaction in human neuronal SK-N-BE cells:
      evaluation by FRET confocal spectral imaging microscopy after dual staining with
      rhodamine-phalloidin and tubulin tracker green.
AB  - Disorganization of the cytoskeleton of neurons has major consequences on the
      transport of neurotransmitters via the microtubule network. The interaction of
      cytoskeleton proteins (actin and tubulin) was studied in neuronal SK-N-BE cells
      treated with tetracosanoic acid (C24:0), which is cytotoxic and increased in
      Alzheimer's disease patients. When SK-N-BE cells were treated with C24:0,
      mitochondrial dysfunctions and a non-apoptotic mode of cell death were observed.
      Fluorescence microscopy revealed shrunken cells with perinuclear condensation of
      actin and tubulin. Impact of C24:0 on actin-microtubule interaction in human
      neuronal SK-N-BE cells: evaluation by FRET confocal spectral imaging microscopy
      after dual staining with rhodamine-phalloidin and tubulin tracker green After
      staining with rhodamine-phalloidin and with an antibody raised against alpha
      /beta-tubulin, modifications of F-actin and alpha-/beta-tubulin levels were
      detected by flow cytometry. Lower levels of alpha-tubulin were found by Western
      blotting. In C24:0-treated cells, spectral analysis and fluorescence recovery
      after photobleaching (FRAP) measured by confocal microscopy proved the existence
      of fluorescence resonance energy transfer (FRET) when actin and tubulin were
      stained with tubulin tracker and rhodamine-phalloidin demonstrating actin and
      tubulin co-localization/interaction. In control cells, no FRET was observed. Our
      data demonstrate quantitative changes in actin and tubulin, and modified
      interactions between actin and tubulin in SK-N-BE cells treated with C24:0. They
      also show that FRET confocal imaging microscopy is an interesting method for
      specifying the impact of cytotoxic compounds on cytoskeleton proteins. 

PMID- 26214026
TI  - Influence of intensive multifunctional neurorehabilitation on neuronal oxidative
      damage in patients with Huntington's disease.
AB  - The influence of intensive multifunctional neurorehabilitation on serum levels of
      Cu/Zn-superoxide dismutase (Cu/Zn-SOD), neuron-specific enolase (NSE), and 8
      hydroxy-2-deoxyguanosine (8-OHdG), as markers of oxidative damage, was evaluated
      in symptomatic patients with Huntington's disease (HD). Improved clinical outcome
      measures were observed after neurorehabilitation. Baseline levels of Cu/Zn-SOD,
      NSE and 8-OHdG were higher than those observed in controls. Cu/Zn-SOD and NSE
      values decreased after neurorehabilitation, but were still higher than those
      measured in controls. Cu/Zn-SOD and NSE correlated positively before (r=0.659;
      p=0.003) and after rehabilitation (r=0.553, p=0.017). 8-OHdG values decreased
      after neurorehabilitation without reaching significance when compared with
      baseline values (p=0.145). No correlation was observed between the measured
      oxidative markers and the assessed clinical outcome measures, either before or
      after neurorehabilitation. The findings reported in the present paper provide
      evidence of the effectiveness of neurorehabilitation in reducing oxidative damage
      in HD patients and underline the limit of serum oxidative markers for the
      evaluation of clinical features of HD. 

PMID- 26214028
TI  - Dual task-related gait changes in patients with mild cognitive impairment.
AB  - Mild cognitive impairment (MCI) entails a high risk of developing Alzheimer's
      dementia. In MCI patients gait impairment, which increases the risk of falls and
      institutionalization, is an early motor sign. A dualtask (DT) paradigm might
      improve the observation of this phenomenon. The aim of this study was to
      investigate motor-cognitive interference in a sample of MCI patients and a group
      of matched healthy controls submitted to DT conditions. To this end, three
      different cognitive tasks were used: counting backwards, short story recall and a
      phonemic fluency task. Overall, the patients, compared with the healthy
      participants, performed worse on the cognitive tasks and showed some degree of
      gait impairment. In the DT conditions, both groups showed significant gait
      disruption independently of the concomitant cognitive task. As regards cognitive
      performance, counting backwards worsened during dual tasking, while short story
      recall improved in both groups. Overall, our results suggest that the use of a DT
      paradigm does not improve the early detection of MCI. Our findings of enhanced
      story recall during walking might have interesting implications for
      rehabilitation of memory function. 

PMID- 26214029
TI  - Minimally symptomatic posterior reversible encephalopathy in Guillain-Barre
      syndrome.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a rare occurrence in
      patients with Guillain-Barre syndrome (GBS). Two patients with neuroradiological
      evidence of PRES without central nervous system (CNS) symptoms were recently
      reported. We present the case of a GBS patient with minimal CNS symptoms and
      magnetic resonance imaging findings consistent with PRES. PRES in GBS might be an
      underestimated condition. It should be suspected in GBS patients in the presence
      of even mild CNS symptoms. A timely PRES diagnosis along with early correction of
      autonomic system dysfunction in GBS patients is recommended to prevent possible
      dangerous CNS complications. 

PMID- 26214030
TI  - Successful treatment with intravenous recombinant tissue plasminogen activator in
      an acute stroke patient presenting with hemiballism.
AB  - A 79-year-old woman with hypertension was evaluated 3 hours and 20 minutes after
      the sudden onset of left-sided weakness which lasted about 15 minutes and was
      followed by involuntary, coarse, flinging movements of the left extremities
      (hemiballistic), occurring every few minutes, and facial asymmetry. Brain
      computed tomography revealed no abnormalities. The patient received intravenous
      thrombolysis with 0.9 mg/kg of alteplase 4 hours after the symptom onset.
      Involuntary movements and central facial nerve paresis subsided within 48 hours
      of the thrombolysis. Magnetic resonance imaging at day 5 revealed restricted
      diffusion within the right globus pallidus, which was a new ischemic lesion.
      Thrombolysis should be considered in hemiballism as a presenting symptom of acute
      stroke. 

PMID- 26214031
TI  - Golgi and Ranvier: from the black reaction to a theory of referred pain.
AB  - In his brief report on the structure of the gray matter of the central nervous
      system (1873), in which he described the "black reaction", Golgi noted the
      ramifications of the axon. This discovery prompted the French histologist Louis
      Antoine Ranvier, one of the first to try the black reaction outside Italy, to
      propose an ingenious theory of referred pain in his Traite technique
      d'histologie. Ranvier suggested that the nerve fibers originating from the
      irritated area and those coming from the region to which the sensation is
      referred converge on the same axon and thus the same cell body, causing the
      spatial dislocation of sensation. This theory of referred pain is a powerful
      example of the extraordinary clinical-physiological impact of the first of
      Golgi's neurocytological discoveries. 

PMID- 26214032
TI  - Drug repurposing and beyond: the fundamental role of pharmacology.

PMID- 26214033
TI  - Delayed gratification: A grey parrot (Psittacus erithacus) will wait for a better
      reward.
AB  - Delay of gratification, the ability to forgo an immediate reward to gain either
      better quality or quantity, has been used as a metric for temporal discounting,
      self-control, and the ability to plan for the future in both humans (particularly
      children) and nonhumans. The task involved can be parsed in several ways, such
      that the subjects can be required to wait, not only for a better or a larger
      reward, but also such that the rewards can either be in view or hidden during the
      delay interval. We have demonstrated that a Grey parrot (Psittacus erithacus)
      trained in the use of English speech could respond to the label "wait" for up to
      15 min, in a task that has many similarities to those used with young children,
      to receive a better quality reward, whether or not the better quality reward or
      the experimenter was in view.

PMID- 26214034
TI  - Development of a Short Version of the Thyroid-Related Patient-Reported Outcome
      ThyPRO.
AB  - BACKGROUND: Thyroid diseases affect quality of life (QoL). The Thyroid-Related
      Patient-Reported Outcome (ThyPRO) is an international comprehensive well
      validated patient-reported outcome, measuring thyroid-related QoL. The current
      version is rather long--85 items. The purpose of the present study was to develop
      an abbreviated version of the ThyPRO, with conserved good measurement properties.
      METHODS: A cross-sectional (N = 907) and a longitudinal sample (N = 435) of
      thyroid patients were analyzed. A graded item response theory (IRT) model was
      fitted to the cross-sectional data. Short-form scales with three items were aimed
      for, by selecting items with best fit according to the IRT model, avoiding cross
      culturally noninvariant items. Seven scales measuring mental and social well
      being and function as well as one overall QoL impact item were analyzed in a
      bifactor model, to develop a supplementary composite score. Short-form scales
      were linked to original scales with IRT-based summed-score-linking. Agreement
      between the short and long form was estimated by agreement plots, intraclass
      correlations, and mean score levels. Responsiveness was compared by relative
      validity indices, clinical validity by ability to detect clinically relevant
      differences, and test-retest reliability by intra-class correlation. RESULTS: One
      four-item scale was not abbreviated and one two-item scale was omitted from the
      short-form. For the 11 scales undergoing abbreviation, 10 with three and one with
      four items were developed. A bifactor model with good overall fit was fitted to
      the composite score, including the single QoL item. Responsiveness and clinical
      validity of the short-form scales were preserved, as were test-retest reliability
      (0.75-0.89). Short- versus long-form intraclass correlations were high (0.89
      0.98), and the mean scale levels were similar. CONCLUSIONS: A 39-item version of
      the ThyPRO, with good measurement properties, was developed and is recommended
      for clinical use.

PMID- 26214035
TI  - Chemiluminescence detection of a protein through the aptamer-controlled catalysis
      of a porphyrin probe.
AB  - Sensitive and selective protein detection based on the aptamer-controlled
      noncovalent porphyrin probe self-assembly is reported for the first time.
      Vascular endothelial growth factor (VEGF) is a predominant biomarker in cancer
      angiogenesis. In this work, a positively charged porphyrin probe, manganese(III)
      meso-tetrakis(N-methylpyridinum-4-yl)porphyrin (Mn-PyP), was prepared. Using it
      as a catalyst, a label-free chemiluminescence (CL) turn-on approach for sensitive
      VEGF detection is developed. Mn-PyP could catalyze the luminol CL reaction. The
      VEGF aptamer could induce aggregation of Mn-PyP. As a result, the Mn-PyP
      catalyzed CL reaction is efficiently suppressed. Upon the addition of VEGF, the
      specific binding of VEGF to the aptamer weakens the interactions between the
      aptamer and Mn-PyP. The Mn-PyP monomers are released, and a turn-on CL signal is
      thus detected. Our method is quite sensitive; 50 pM of VEGF could be easily
      detected. It is also very selective against other proteins. Our assay provides an
      aptamer-based efficient way for protein quantification. 

PMID- 26214036
TI  - Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of
      D2 in Myocytes.
AB  - The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in
      skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly
      leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed
      Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin
      light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental
      stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50%
      in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in
      isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured
      soleus T3 content and found it to be normal. We also looked at the expression of
      T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, alpha-actin,
      myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in
      neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2
      activity in control animals. In adult soleus the baseline level of D2 activity
      was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of
      five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals
      performed indistinguishably from controls on a treadmill test, running for
      approximately 16 minutes and reached a speed of about 23 m/min; muscle strength
      was about 0.3 mN/m.g body weight in SKM-D2KO and control ankle muscles. In
      conclusion, there are multiple sources of D2 in the mouse SKM, and its role is
      limited in postnatal skeletal muscle fibers. 

PMID- 26214037
TI  - Coenzyme Q10 Prevents Insulin Signaling Dysregulation and Inflammation Prior to
      Development of Insulin Resistance in Male Offspring of a Rat Model of Poor
      Maternal Nutrition and Accelerated Postnatal Growth.
AB  - Low birth weight and rapid postnatal growth increases the risk of developing
      insulin resistance and type 2 diabetes in later life. However, underlying
      mechanisms and potential intervention strategies are poorly defined. Here we
      demonstrate that male Wistar rats exposed to a low-protein diet in utero that had
      a low birth weight but then underwent postnatal catch-up growth (recuperated
      offspring) had reductions in the insulin signaling proteins p110-beta (13% +/- 6%
      of controls [P < .001]) and insulin receptor substrate-1 (39% +/- 10% of controls
      [P < .05]) in adipose tissue. These changes were not accompanied by any change in
      expression of the corresponding mRNAs, suggesting posttranscriptional regulation.
      Recuperated animals displayed evidence of a proinflammatory phenotype of their
      adipose tissue with increased IL-6 (139% +/- 8% [P < .05]) and IL1-beta (154% +/-
      16% [P < .05]) that may contribute to the insulin signaling protein
      dysregulation. Postweaning dietary supplementation of recuperated animals with
      coenzyme Q (CoQ10) (1 mg/kg of body weight per day) prevented the programmed
      reduction in insulin receptor substrate-1 and p110-beta and the programmed
      increased in IL-6. These findings suggest that postweaning CoQ10 supplementation
      has antiinflammatory properties and can prevent programmed changes in insulin
      signaling protein expression. We conclude that CoQ10 supplementation represents
      an attractive intervention strategy to prevent the development of insulin
      resistance that results from suboptimal in utero nutrition. 

PMID- 26214038
TI  - Iodine(III)-Mediated Oxy-fluorination of Alkenyl Oximes: An Easy Path to
      Monofluoromethyl-Substituted Isoxazolines.
AB  - A highly regioselective intramolecular oxy-fluorination of alkenyl oximes was
      achieved. This new transformation represents an efficient method for the
      preparation of monofluoromethyl-substituted isoxazolines. The synthetic
      application of the oxy-fluorination product was demonstrated by a one-step
      synthesis of monofluoromethyl-substituted beta-hydroxyl ketone derivatives. 

PMID- 26214040
TI  - A Candidate Dengue Vaccine Walks a Tightrope.

PMID- 26214041
TI  - Lignin-Based Triple Shape Memory Polymers.
AB  - Lignin-based triple shape memory polymers comprised of both permanent covalent
      cross-links and physical cross-links have been synthesized. A mixing phase with
      poly(ester-amine) and poly(ester-amide) network having two distinct glass
      transitions was hot mixed with more structurally homogenized methanol soluble
      lignin fraction by one-pot, two-step method. Triple shape properties arise from
      the combined effect of the glass transition of polyester copolymers and lignin
      and the dissociation of self-complementary hydrogen bonding and cross-link
      density. The percentage of recovery in each stage was investigated and it was
      proved that the first recovery is related with lignin-poly(ester-amine) rich
      network and the second recovery stage is related with lignin-poly(ester-amide)
      rich network. The thermal and mechanical properties of the lignin-copolymer
      networks were also investigated using differential scanning calorimetry and
      dynamic mechanical analysis. 

PMID- 26214039
TI  - Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease.
AB  - BACKGROUND: A candidate tetravalent dengue vaccine is being assessed in three
      clinical trials involving more than 35,000 children between the ages of 2 and 16
      years in Asian-Pacific and Latin American countries. We report the results of
      long-term follow-up interim analyses and integrated efficacy analyses. METHODS:
      We are assessing the incidence of hospitalization for virologically confirmed
      dengue as a surrogate safety end point during follow-up in years 3 to 6 of two
      phase 3 trials, CYD14 and CYD15, and a phase 2b trial, CYD23/57. We estimated
      vaccine efficacy using pooled data from the first 25 months of CYD14 and CYD15.
      RESULTS: Follow-up data were available for 10,165 of 10,275 participants (99%) in
      CYD14 and 19,898 of 20,869 participants (95%) in CYD15. Data were available for
      3203 of the 4002 participants (80%) in the CYD23 trial included in CYD57. During
      year 3 in the CYD14, CYD15, and CYD57 trials combined, hospitalization for
      virologically confirmed dengue occurred in 65 of 22,177 participants in the
      vaccine group and 39 of 11,089 participants in the control group. Pooled relative
      risks of hospitalization for dengue were 0.84 (95% confidence interval [CI], 0.56
      to 1.24) among all participants, 1.58 (95% CI, 0.83 to 3.02) among those under
      the age of 9 years, and 0.50 (95% CI, 0.29 to 0.86) among those 9 years of age or
      older. During year 3, hospitalization for severe dengue, as defined by the
      independent data monitoring committee criteria, occurred in 18 of 22,177
      participants in the vaccine group and 6 of 11,089 participants in the control
      group. Pooled rates of efficacy for symptomatic dengue during the first 25 months
      were 60.3% (95% CI, 55.7 to 64.5) for all participants, 65.6% (95% CI, 60.7 to
      69.9) for those 9 years of age or older, and 44.6% (95% CI, 31.6 to 55.0) for
      those younger than 9 years of age. CONCLUSIONS: Although the unexplained higher
      incidence of hospitalization for dengue in year 3 among children younger than 9
      years of age needs to be carefully monitored during long-term follow-up, the risk
      among children 2 to 16 years of age was lower in the vaccine group than in the
      control group. (Funded by Sanofi Pasteur; ClinicalTrials.gov numbers,
      NCT00842530, NCT01983553, NCT01373281, and NCT01374516.).

PMID- 26214042
TI  - The Clinical Significance of Abnormal Tim-3 Expression on NK Cells from Patients
      with Gastric Cancer.
AB  - AIM: To investigate the clinical significance of Tim-3 (T-cell immunoglobulin-
      and mucin-domain-containing molecule 3) expression in natural killer (NK) cells
      from patients with gastric cancer. MATERIALS AND METHODS: Sixty-two patients with
      gastric cancer and 32 healthy controls were recruited for this study. Tim-3
      expression in peripheral blood samples was analyzed using flow cytometry. The
      expression pattern of Tim-3 on NK cells was also confirmed using a gastric cancer
      bearing mouse model. To further investigate the mechanisms that regulate Tim-3
      expression, T-bet(-/-), Eomes(-/-), and Eomes/T-bet double knockout mice were
      utilized. Additionally, we statistically analyzed the clinical significance of
      Tim-3 expression on NK cells. RESULTS: We found that the levels of Tim-3 in NK
      cells obtained from patients with gastric cancer were significantly higher than
      the levels in healthy controls. Clinical analyses showed that Tim-3 levels on NK
      cells were associated with advanced tumor stage. In a tumor-bearing mouse model,
      Tim-3 levels in NK cells increased with tumor growth, indicating that tumor
      progression could induce Tim-3 expression in NK cells. Finally, we report that T
      bet is a key factor involved in regulating Tim-3 expression. CONCLUSION: Our data
      indicate that Tim-3 expression on NK cells is regulated by T-bet, and that Tim-3
      levels correlate with advanced stages of gastric cancer.

PMID- 26214044
TI  - Analysis of Mitochondrial Network Morphology in Cultured Myoblasts from Patients
      with Mitochondrial Disorders.
AB  - Mitochondrial morphology was studied in cultivated myoblasts obtained from
      patients with mitochondrial disorders, including CPEO, MELAS and TMEM70
      deficiency. Mitochondrial networks and ultrastructure were visualized by
      fluorescence microscopy and transmission electron microscopy, respectively. A
      heterogeneous picture of abnormally sized and shaped mitochondria with
      fragmentation, shortening, and aberrant cristae, lower density of mitochondria
      and an increased number of "megamitochondria" were found in patient myoblasts.
      Morphometric Fiji analyses revealed different mitochondrial network properties in
      myoblasts from patients and controls. The small number of cultivated myoblasts
      required for semiautomatic morphometric image analysis makes this tool useful for
      estimating mitochondrial disturbances in patients with mitochondrial disorders. 

PMID- 26214045
TI  - The Influence of Exercise on Cognitive Performance in Normobaric Hypoxia.
AB  - Although previous reports indicate that exercise improves cognitive function in
      normoxia, the influence of exercise on cognitive function in hypoxia is unknown.
      The purpose of this study was to determine if the impaired cognitive function in
      hypoxia can be restored by low to moderate intensity exercise. Sixteen young
      healthy men completed the ANAM versions of the Go/No-Go task (GNT) and Running
      Memory Continuous Performance Task (RMCPT) in normoxia to serve as baseline (B
      Norm) (21% O2). Following 60 minutes of exposure to normobaric hypoxia (B-Hypo)
      (12.5% O2), these tests were repeated at rest and during cycling exercise at 40%
      and 60% of adjusted Vo2max. At B-Hypo, the % correct (p<=0.001) and throughput
      score (p<=0.001) in RMCPT were significantly impaired compared to B-Norm. During
      exercise at 40% (p=0.023) and 60% (p=0.006) of adjusted Vo2max, the throughput
      score in RMCPT improved compared to B-Hypo, and there was no significant
      difference in throughput score between the two exercise intensities. Mean
      reaction time also improved at both exercise intensities compared to B-Hypo
      (p<=0.028). Both peripheral oxygen saturation (Spo2) and regional cerebral oxygen
      saturation (rSo2) significantly decreased during B-Hypo (p<=0.001) and further
      decreased at 40% (p<=0.05) and 60% (p<=0.039) exercise. There was no significant
      difference in Spo2 or rSo2 between two exercise intensities. These data indicate
      that low to moderate exercise (i.e., 40%-60% adjusted Vo2max) may attenuate the
      risk of impaired cognitive function that occurs in hypoxic conditions.

PMID- 26214043
TI  - Long-Range Optical Coherence Tomography of the Neonatal Upper Airway for Early
      Diagnosis of Intubation-related Subglottic Injury.
AB  - RATIONALE: Subglottic edema and acquired subglottic stenosis are potentially
      airway-compromising sequelae in neonates following endotracheal intubation. At
      present, no imaging modality is capable of in vivo diagnosis of subepithelial
      airway wall pathology as signs of intubation-related injury. OBJECTIVES: To use
      Fourier domain long-range optical coherence tomography (LR-OCT) to acquire
      micrometer-resolution images of the airway wall of intubated neonates in a
      neonatal intensive care unit setting and to analyze images for histopathology and
      airway wall thickness. METHODS: LR-OCT of the neonatal laryngotracheal airway was
      performed a total of 94 times on 72 subjects (age, 1-175 d; total intubation, 1
      104 d). LR-OCT images of the airway wall were analyzed in MATLAB. Medical records
      were reviewed retrospectively for extubation outcome. MEASUREMENTS AND MAIN
      RESULTS: Backward stepwise regression analysis demonstrated a statistically
      significant association between log(duration of intubation) and both laryngeal (P
      < 0.001; multiple r(2) = 0.44) and subglottic (P < 0.001; multiple r(2) = 0.55)
      airway wall thickness. Subjects with positive histopathology on LR-OCT images had
      a higher likelihood of extubation failure (odds ratio, 5.9; P = 0.007). Longer
      intubation time was found to be significantly associated with extubation failure.
      CONCLUSIONS: LR-OCT allows for high-resolution evaluation and measurement of the
      airway wall in intubated neonates. Our data demonstrate a positive correlation
      between laryngeal and subglottic wall thickness and duration of intubation,
      suggestive of progressive soft tissue injury. LR-OCT may ultimately aid in the
      early diagnosis of postintubation subglottic injury and help reduce the
      incidences of failed extubation caused by subglottic edema or acquired subglottic
      stenosis in neonates. Clinical trial registered with www.clinicaltrials.gov (NCT
      00544427).

PMID- 26214046
TI  - Peptide Bioink: Self-Assembling Nanofibrous Scaffolds for Three-Dimensional
      Organotypic Cultures.
AB  - Printable scaffolds with adequate mechanical strength and stiffness are sought
      after to ensure viability of printed cells and tissues. We report the first
      peptide bioinks-lysine-containing hexapeptides that self-assemble into stable,
      nanofibrous three-dimensional hydrogels with unprecedented stiffness of up to 40
      kPa. These biocompatible scaffolds support the three-dimensional culture of human
      stem cells and differentiation of primary cells into organotypic
      (gastrointestinal and skin) structures for high-throughput screening, diagnosis,
      and tissue engineering. 

PMID- 26214047
TI  - Cystochromones, Unusual Chromone-Containing Polyketides from the Myxobacterium
      Cystobacter sp. MCy9104.
AB  - Seven new chromone-containing polyketides, termed cystochromones A-G, were
      isolated from the myxobacterial strain Cystobacter sp. MCy9104. Their structures
      were elucidated using comprehensive NMR spectroscopy and HR-MS/MS. Cystochromones
      bear a pentadecyl moiety unusually attached at C-5 of the chromone ring.
      Moreover, isotope-labeled substrate feeding experiments and NMR analysis
      suggested a hybrid iso-fatty acid and polyketide synthase biosynthetic pathway
      for these secondary metabolites. 

PMID- 26214048
TI  - Boron Nitride Surface Activity as Route to Composite Dielectric Films.
AB  - The propensity of boron nitride sheets to stack creates obstacles for their
      application as multifunctional materials despite their unique thermal,
      mechanical, and electrical properties. To address this challenge, we use a
      combination of molecular dynamics simulations and experimental techniques to
      demonstrate surfactant-like properties of BN sheets at the interface between
      immiscible solvents. The spreading of two-dimensional BN sheets at a high-energy
      oil/water interface lowers the free energy of the system, creating films of
      overlapping BN sheets that are more thermodynamically favorable than stacked
      sheets. Coating such films onto polymers results in composite materials with
      exceptional barrier and dielectric properties. 

PMID- 26214049
TI  - New cyclic tetrapeptide from the coral-derived endophytic bacteria Brevibacterium
      sp. L-4 collected from the South China Sea.
AB  - One new cyclic tetrapeptide cyclic-(Tyr-Ala-Leu-Ser) (1) along with four natural
      compounds firstly obtained 3H-imidazole-4-carboxylic acid (2), 2-methyl-3H
      imidazole-4-carboxylic acid (3), 3-ethylidene-6-isopropyl-piperazine-2,5-dione
      (4), and 3-isobutylidene-6-methyl piperazine-2,5-dione (5) have been isolated
      from the coral derived endophytic bacteria Brevibacterium sp. L-4 collected from
      the South China Sea. Their structures were elucidated through spectroscopic
      techniques including NMR (1D and 2D), MS, and EA, and their relative
      configurations were also assigned by NMR analysis. 

PMID- 26214050
TI  - The natural history of neural tube defects in the setting of an Irish tertiary
      referral foetal medicine unit.
AB  - Neural tube defects (NTDs) carry a heavy burden for affected individuals and
      their family. Physical and neurological outcome measures may help in counselling
      couples. The aim of this audit was to review all cases of NTDs seen at a tertiary
      referral foetal medicine unit. Cases were identified from obstetric, neonatal and
      neurosurgical records. Thirty-six cases of NTDs were identified. Of the 36, 25%
      (n = 9, one trisomy 18) opted for termination of pregnancy abroad. Of the
      remaining 27, 19% (n = 5) died in the antepartum period. 81% (n = 22) were
      liveborn with four neonatal deaths (one trisomy 18). Of 15 cases, 14 had
      neurosurgical repair within a median time of 3 days and 9 of these also had a
      ventriculoperitoneal shunt inserted. Antenatal ultrasound accurately diagnosed
      lesion level in the majority of cases. The survival rate for babies diagnosed
      with non-lethal neural tubes defects is high when multidisciplinary care is
      initiated early. 

PMID- 26214051
TI  - Antioxidative properties of ginsenoside Ro against UV-B-induced oxidative stress
      in human dermal fibroblasts.
AB  - Ginsenoside Ro (Ro), an oleanolic acid-type ginsenoside, exhibited suppressive
      activities on reactive oxygen species (ROS) and matrix metalloproteinase-2 (MMP
      2) elevation in UV-B-irradiated fibroblasts. Ro could overcome the reduction of
      the total glutathione (GSH) contents in UV-B-irradiated fibroblasts. Ro could not
      interfere with cell viabilities in UV-B-irradiated fibroblasts. Collectively, Ro
      possesses a potential skin anti-photoaging property against UV-B radiation in
      fibroblasts. 

PMID- 26214052
TI  - A chain kinematic model to assess the movement of lower-limb including wobbling
      masses.
AB  - Computer simulation models have shown that wobbling mass on the lower limb
      affects the joint kinetics. Our objective was to propose a non-invasive method to
      estimate bones and wobbling mass kinematics in the lower limb during hopping. The
      chain kinematic model has set degrees of freedom at the joints and free wobbling
      bodies. By comparison to a model without wobbling bodies, the marker residual was
      reduced by 20% but the joint kinematics remains unchanged. Wobbling bodies'
      displacements reached 6.9 +/- 3.5 degrees  and 6.9 +/- 2.4 mm relative to the
      modelled bones. This original method is a first step to assess wobbling mass
      effect on joint kinetics.

PMID- 26214054
TI  - Prevalence and predictors of type 2 diabetes mellitus in people with bipolar
      disorder: a systematic review and meta-analysis.
AB  - OBJECTIVE: This systematic review and meta-analysis assessed the prevalence and
      predictors of type 2 diabetes mellitus (T2DM) in people with bipolar disorder. We
      also compared the prevalence of T2DM in people with bipolar disorder versus age-
      and gender-matched healthy controls. DATA SOURCES: PubMed, EMBASE, PsycARTICLES,
      and CINAHL were searched from inception till October 23, 2014 using the medical
      subject headings terms bipolar disorder AND diabetes OR glucose. There was no
      language restriction. Observational studies including retrospective, cross
      sectional, and prospective designs were eligible if they included participants
      with bipolar disorder diagnosed according to recognized diagnostic criteria (DSM
      or ICD). STUDY SELECTION: Nineteen studies were included (n = 18,060; 54.8%
      male). DATA EXTRACTION: Two independent authors extracted data in accordance with
      the meta-analysis of observational studies in epidemiology guidelines and PRISMA
      statement. A random effects meta-analysis was utilized. RESULTS: The overall
      prevalence of T2DM was 9.4% (95% CI, 6.5%-12.7%). Compared with age- and gender
      matched controls (n = 783,049; 48.7% male), people with bipolar disorder (n =
      6,595; 48.6% male) had double the risk of T2DM (relative risk = 1.98; 95% CI, 1.6
      2.4, P < .001). No significant moderators were found. In an exploratory
      regression analysis, the variance in T2DM prevalence in the background population
      was associated with the variance in T2DM prevalence in people with bipolar
      disorder (5 studies, n = 4,983) (r(2) = 0.85, t = 4.09, P = .03). CONCLUSIONS:
      T2DM is significantly more common in people with bipolar disorder than in healthy
      controls of similar age and sex. The current meta-analysis furthermore indicates
      that changes in food, built, and social environments are needed in order to curb
      the diabetes epidemic in this high-risk population.

PMID- 26214055
TI  - A palladium-doped ceria@carbon core-sheath nanowire network: a promising catalyst
      support for alcohol electrooxidation reactions.
AB  - A novel palladium-doped ceria and carbon core-sheath nanowire network (Pd-CeO2@C
      CSNWN) is synthesized by a template-free and surfactant-free solvothermal
      process, followed by high temperature carbonization. This hierarchical network
      serves as a new class of catalyst support to enhance the activity and durability
      of noble metal catalysts for alcohol oxidation reactions. Its supported Pd
      nanoparticles, Pd/(Pd-CeO2@C CSNWN), exhibit >9 fold increase in activity toward
      the ethanol oxidation over the state-of-the-art Pd/C catalyst, which is the
      highest among the reported Pd systems. Moreover, stability tests show a virtually
      unchanged activity after 1000 cycles. The high activity is mainly attributed to
      the superior oxygen-species releasing capability of Pd-doped CeO2 nanowires by
      accelerating the removal of the poisoning intermediate. The unique interconnected
      one-dimensional core-sheath structure is revealed to facilitate immobilization of
      the metal catalysts, leading to the improved durability. This core-sheath
      nanowire network opens up a new strategy for catalyst performance optimization
      for next-generation fuel cells. 

PMID- 26214053
TI  - Association between SLC30A8 rs13266634 Polymorphism and Type 2 Diabetes Risk: A
      Meta-Analysis.
AB  - BACKGROUND: Accumulating but inconsistent data about the role of rs13266634
      variant of SLC30A8 in type 2 diabetes have been reported, partly due to small
      sample sizes and non-identical ethnicity. MATERIAL AND METHODS: We searched
      PubMed and Cochrane Library to identify eligible studies and extract data of
      baseline characteristics, genotype count, odds ratio (OR), and 95% confidence
      interval (CI). Both adjusted OR with 95% CI and genotype counts were employed to
      assess the association. Genotype data were further pooled to provide estimates
      under different genetic models and the most appropriate model was determined.
      Sensitivity and cumulative analysis were conducted to assure the strength of
      results. RESULTS: Fifty-five datasets of 39 studies (including 38 of 24 with
      genotype count) were included. Significant associations were found in allelic
      contrasts using adjusted ORs and raw genotype count, respectively, overall in
      Asian and European populations (overall: OR=1.147/1.157, 95% CI 1.114-1.181/1.135
      1.180; Asian: OR=1.186/1.165, 95% CI 1.150-1.222/1.132-1.198; European:
      OR=1.100/1.151, 95% CI 1.049-1.153/1.120-1.183; All p=0.00), but not in African
      populations (African: OR=1.255/1.111, 95% CI 0.964-1.634/0.908-1.360,
      p=0.091/0.305). Further analysis with genotype count under different genetic
      models all showed that individuals with CC genotype had 33.0% and 16.5% higher
      risk of type 2 diabetes than those carrying TT and CT genotypes, respectively,
      under the most likely codominant model. Cumulative analysis indicated gradually
      improved precision of estimation after studies accumulated. CONCLUSIONS: Our
      results suggest that rs13266634 may be an important genetic factor of type 2
      diabetes risk among Asian and European but not African populations.

PMID- 26214056
TI  - Mechanistic details of energy transfer and soft landing in ala2-H(+) collisions
      with a F-SAM surface.
AB  - Previous chemical dynamics simulations (Phys. Chem. Chem. Phys., 2014, 16, 23769
      23778) were analyzed to delineate atomistic details for collision of N-protonated
      dialanine (ala2-H(+)) with a C8 perfluorinated self-assembled monolayer (F-SAM)
      surface. Initial collision energies Ei of 5-70 eV and incident angles thetai of 0
      degrees  and 45 degrees , with the surface normal, were considered. Four
      trajectory types were identified: (1) direct scattering; (2) temporary
      sticking/physisorption on top of the surface; (3) temporary penetration of the
      surface with additional physisorption on the surface; and (4) trapping on/in the
      surface, by physisorption or surface penetration, when the trajectory is
      terminated. Direct scattering increases from 12 to 100% as Ei is increased from 5
      to 70 eV. For the direct scattering at 70 eV, at least one ala2-H(+) heavy atom
      penetrated the surface for all of the trajectories. For ~33% of the trajectories
      all eleven of the ala2-H(+) heavy atoms penetrated the F-SAM at the time of
      deepest penetration. The importance of trapping decreased with increase in Ei,
      decreasing from 84 to 0% with Ei increase from 5 to 70 eV at thetai = 0 degrees .
      Somewhat surprisingly, the collisional energy transfers to the F-SAM surface and
      ala2-H(+) are overall insensitive to the trajectory type. The energy transfer to
      ala2-H(+) is primarily to vibration, with the transfer to rotation ~10% or less.
      Adsorption and then trapping of ala2-H(+) is primarily a multi-step process, and
      the following five trapping mechanisms were identified: (i) physisorption
      penetration-physisorption (phys-pen-phys); (ii) penetration-physisorption
      penetration (pen-phys-pen); (iii) penetration-physisorption (pen-phys); (iv)
      physisorption-penetration (phys-pen); and (v) only physisorption (phys). For Ei =
      5 eV, the pen-phys-pen, pen-phys, phys-pen, and phys trapping mechanisms have
      similar probabilities. For 13.5 eV, the phys-pen mechanism, important at 5 eV, is
      unimportant. The radius of gyration of ala2-H(+) was calculated once it is
      trapped on/in the F-SAM surface and trapping decreases the ion's compactness, in
      part by breaking hydrogen bonds. The ala2-H(+) + F-SAM simulations are compared
      with the penetration and trapping dynamics found in previous simulations of
      projectile + organic surface collisions. 

PMID- 26214057
TI  - Handle Shape Affects the Grip Force Distribution and the Muscle Loadings During
      Power Grip Tasks.
AB  - The objectives of this study were to investigate the effect of handle shape on
      the grip force distribution in the hand and on the muscle forces during maximal
      power grip tasks. Eleven subjects maximally grasped 3 handles with different
      external shapes (circular, elliptic, and double-frustum). A handle dynamometer,
      equipped with both a force sensor and a pressure map, was used to record the
      forces exerted at the hand/handle interface. The finger and wrist joint postures
      were also computed from synchronized kinematic measurement. These processed data
      were then used as input of a biomechanical hand model to estimate muscle forces.
      The results showed that handle shape influences the maximal grip force, the grip
      force distribution, and the finger joint postures. Particularly, we observed that
      the elliptical shape resulted in a 6.6% lower maximal grip force compared with
      the circular and double-frustum handle. Concomitantly, the estimated muscle
      forces also varied significantly according to the handle shape, with up to 48%
      differences for the flexor digitorum superficialis muscle for example.
      Interestingly, different muscle coordination strategies were observed depending
      on the handle shape, therefore suggesting a potential influence of these
      geometrical characteristics on pathological risks such as tendonitis. 

PMID- 26214058
TI  - A simple model of burst nucleation.
AB  - We introduce a comprehensive quantitative treatment for burst nucleation (BN)-a
      kinetic pathway toward self-assembly or crystallization defined by an extended
      post-supersaturation induction period, followed by a burst of nucleation, and
      finally the growth of existing stable assemblages absent the formation of new
      ones-based on a hybrid mean field rate equation model incorporating thermodynamic
      treatment of the saturated solvent from classical nucleation theory. A key
      element is the inclusion of a concentration-dependent critical nucleus size,
      determined self-consistently along with the subcritical cluster population
      density. The model is applied to an example experimental study of crystallization
      in tetracene films prepared by organic vapor-liquid-solid deposition, where good
      agreement is observed with several aspects of the experiment using a single,
      physically well-defined adjustable parameter. The model predicts many important
      features of the experiment, and can be generalized to describe other self
      organizing systems exhibiting BN kinetics. 

PMID- 26214059
TI  - Organopromoted direct synthesis of 6-iodo-3-methylthioimidazo[1,2-a]pyridines via
      convergent integration of three self-sorting domino sequences.
AB  - An NH2CN-promoted convergent integration of three self-sorting domino sequences
      is described for the construction of 6-iodo-3-methylthioimidazo[1,2-a]pyridines
      from aryl methyl ketones and 2-aminopyridines. This strategy allows the
      construction of an imidazo[1,2-a]pyridine ring along with methylthiolation at C-3
      and iodination at C-6. Preliminary mechanistic studies indicate that this process
      terminates at the iodination stage without Kornblum oxidation in the presence of
      I2 and DMSO. 

PMID- 26214060
TI  - The remarkable activity and stability of a dye-sensitized single molecular layer
      MoS2 ensemble for photocatalytic hydrogen production.
AB  - Single layer MoS2 synthesized by exfoliation with Li is demonstrated to take up
      the dye molecule, Eosin Y, with strong binding affinity via sulfur vacancies.
      This dye-sensitized single layer MoS2 ensemble exhibits remarkable activity and
      stability for photocatalytic hydrogen production from water. 

PMID- 26214061
TI  - Enantio-differentiation of molecules with diverse functionalities using a single
      probe.
AB  - This study reports (1S,2S)-N,N'-dihydroxy-N,N'-bis(diphenylacetyl)-1,2
      cyclohexanediamine, a C2 symmetric chiral hydroxamic acid ((S)-CBHA-DPA), as a
      unique probe for discrimination of molecules with diverse functionalities. The
      proposed CSA is also utilized for the accurate measurement of enantiomeric
      excess. 

PMID- 26214062
TI  - Correlation between hierarchical structure of crystal networks and macroscopic
      performance of mesoscopic soft materials and engineering principles.
AB  - This review examines how the concepts and ideas of crystallization can be
      extended further and applied to the field of mesoscopic soft materials. It
      concerns the structural characteristics vs. the macroscopic performance, and the
      formation mechanism of crystal networks. Although this subject can be discussed
      in a broad sense across the area of mesoscopic soft materials, our main focus is
      on supramolecular materials, spider and silkworm silks, and biominerals. First,
      the occurrence of a hierarchical structure, i.e. crystal network and domain
      network structures, will facilitate the formation kinetics of mesoscopic phases
      and boost up the macroscopic performance of materials in some cases (i.e. spider
      silk fibres). Second, the structure and performance of materials can be
      correlated in some way by the four factors: topology, correlation length,
      symmetry/ordering, and strength of association of crystal networks. Moreover,
      four different kinetic paths of crystal network formation are identified, namely,
      one-step process of assembly, two-step process of assembly, mixed mode of
      assembly and foreign molecule mediated assembly. Based on the basic mechanisms of
      crystal nucleation and growth, the formation of crystal networks, such as
      crystallographic mismatch (or noncrystallographic) branching (tip branching and
      fibre side branching) and fibre/polymeric side merging, are reviewed. This
      facilitates the rational design and construction of crystal networks in
      supramolecular materials. In this context, the (re-)construction of a
      hierarchical crystal network structure can be implemented by thermal,
      precipitate, chemical, and sonication stimuli. As another important class of soft
      materials, the unusual mechanical performance of spider and silkworm silk fibres
      are reviewed in comparison with the regenerated silk protein derivatives. It
      follows that the considerably larger breaking stress and unusual breaking strain
      of spider silk fibres vs. silkworm silk fibres can be interpreted according to
      the synergistically correlated hierarchical structures of the domain and crystal
      networks, which can be quantified by the hierarchical structural correlation and
      the four structural parameters. Based on the concept of crystal networks, the new
      understanding acquired will transfer the research and engineering of mesoscopic
      materials, particularly, soft functional materials, to a new phase. 

PMID- 26214063
TI  - Catalytic polymeric nanocomposites via cucurbit[n]uril host-guest interactions.
AB  - Polymeric nanocomposites were prepared by using cucurbit[7]uril as a
      'supramolecular anchor', as well as stabilising ligand to immobilise catalytic
      transition-metal nanoparticles on the surface of methyl viologen-bearing
      polymeric colloids. This facile and spontaneous supramolecular approach allows
      for control over size, morphology and composition of the nanocomposites. The
      small metallic nanoparticles impart the nanocomposites with great potential in
      catalysis. 

PMID- 26214064
TI  - Photochemistry of nitrate chemisorbed on various metal oxide surfaces.
AB  - Atmospheric aerosols are known to provide an important surface for gas-solid
      interfaces that can lead to heterogeneous reactions impacting tropospheric
      chemistry. In this work, alpha-Fe2O3, TiO2, gamma-Al2O3, SiO2 and ZnO, common
      components of atmospheric aerosols, served as models to investigate the gas-solid
      interface of nitric acid with aerosols in the presence of simulated solar
      radiation. Adsorbed nitrate and gaseous products can be continuously monitored
      with infrared spectroscopy (IR). Kinetic studies of adsorbed species were carried
      out using attenuated total reflectance infrared spectroscopy (ATR-FTIR). Ex situ
      simultaneous infrared spectroscopy of gas-phase products using a 2 m long path
      cell allowed the detection of gaseous products at early stages of the
      heterogeneous photochemical reaction. In addition, photoactive gaseous products,
      such as HONO, were detected as gas analysis was carried out outside the region of
      irradiation. All reactions were found to be first order with respect to adsorbed
      nitric acid and yielded gas-phase products such as NO, NO2, N2O4, N2O, and HONO.
      While the correlation between semiconductor properties of the metal oxide and the
      heterogeneous photochemical rate constant (j) is not direct, the semiconductor
      properties were found to play a role in the formation of relatively high
      proportions of greenhouse gas nitrous oxide (N2O). 

PMID- 26214065
TI  - No influence of CYP2D6*10 genotype and phenotype on the pharmacokinetics of
      nebivolol in healthy Chinese subjects.
AB  - WHAT IS KNOWN AND OBJECTIVE: Nebivolol, a clinically important antihypertensive
      drug, mainly metabolized by cytochrome P450 (CYP) 2D6, shows wide interindividual
      variability in pharmacokinetics. The CYP2D6*10 allele (100C>T; rs1065852),
      present at a high frequency in the Chinese population, is associated with
      alteration in the pharmacokinetics of many drugs, but its effect on the
      pharmacokinetics of nebivolol is unknown. The aim of our study was to investigate
      whether the CYP2D6*10 genotype and phenotype are associated with changes in the
      pharmacokinetics of nebivolol in Chinese subjects. METHODS: Twenty-four healthy
      subjects were divided into three groups according to CYP2D6*1/*1 (n = 7),
      CYP2D6*1/*10 (n = 5) and CYP2D6*10/*10 (n = 12) genotypes. The *1/*1 homozygotes
      and *1/*10 heterozygotes were C allele carriers. All subjects received oral
      single dose of nebivolol and dextromethorphan. Blood and urine samples were
      gathered at various times. RESULTS: There were no statistically significant
      differences in the pharmacokinetics of nebivolol between the three CYP2D6*10
      genotypes, and no gene-dose effect was seen. The pharmacokinetic parameters of
      CYP2D6*10/*10 subjects were also similar to those of CYP2D6*1 carriers. A weak
      relationship between CYP2D6 phenotype and nebivolol clearance was found. WHAT IS
      NEW AND CONCLUSION: The CYP2D6*10 genotype and phenotype were not associated with
      significant alterations in the pharmacokinetics of nebivolol. CYP2D6*10 alone
      does not account for the large interindividual differences observed in the
      disposition of nebivolol among Chinese healthy subjects.

PMID- 26214066
TI  - Gray Matter Alterations in Young Children with Autism Spectrum Disorders:
      Comparing Morphometry at the Voxel and Regional Level.
AB  - BACKGROUND AND PURPOSE: Sophisticated algorithms to infer disease diagnosis,
      pathology progression and patient outcome are increasingly being developed to
      analyze brain MRI data. They have been successfully implemented in a variety of
      diseases and are currently investigated in the field of neuropsychiatric
      disorders, including autism spectrum disorder (ASD). We aim to test the ability
      to predict ASD from subtle morphological changes in structural magnetic resonance
      imaging (sMRI). METHODS: The analysis of sMRI of a cohort of male ASD children
      and controls matched for age and nonverbal intelligence quotient (NVIQ) has been
      carried out with two widely used preprocessing software packages (SPM and
      Freesurfer) to extract brain morphometric information at different spatial
      scales. Then, support vector machines have been implemented to classify the brain
      features and to localize which brain regions contribute most to the ASD-control
      separation. RESULTS: The features extracted from the gray matter subregions
      provide the best classification performance, reaching an area under the receiver
      operating characteristic curve (AUC) of 74%. This value is enhanced to 80% when
      considering only subjects with NVIQ over 70. CONCLUSIONS: Despite the subtle
      impact of ASD on brain morphology and a limited cohort size, results from sMRI
      based classifiers suggest a consistent network of altered brain regions.

PMID- 26214067
TI  - Polymorphisms in CYP-mediated arachidonic acid routes affect the outcome of renal
      transplantation.
AB  - BACKGROUND: Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP) enzymes
      to vasoactive metabolites (mainly epoxyeicosatrienoic acids) which are known to
      play a protective role against damaging processes that may occur after re
      oxygenation of the graft. We aimed to investigate whether the presence of
      functional polymorphisms along these metabolic routes may play a role in the
      outcome of renal transplantation. DESIGN: One-hundred and forty Caucasian renal
      transplant recipients and 137 donors were included. We determined the presence of
      seven common functional polymorphisms in the five genes governing the CYP
      mediated AA metabolic pathway (CYP2C8, CYP2C9, CYP2J2, CYP4A11 and CYP4F2).
      Associations with parameters and events related to graft function and survival
      were retrospectively investigated throughout the first year after grafting.
      RESULTS: The CYP2J2*7 allele of the donor was significantly associated with
      higher risk for delayed graft function [OR = 4.40 (1.45-13.37), P < 0.01] and
      lower death-censored graft survival [107.90 (84.19-131.62) vs. 176.89 (166.47
      187.32) months for CYP2J2*1/*1 grafts; log-rank P = 0.015]. In addition, patients
      whose donors carried the CYP4A11 434S variant of the F434S polymorphism displayed
      impaired creatinine clearance, with statistically significant differences vs.
      434FF subjects throughout the whole period of study (P < 0.05, P < 0.01, P <
      0.001 and P < 0.05 for 1 week, 1 month, 5 months and 1 year after grafting,
      respectively). CONCLUSIONS: Taken together, these results indicate that
      variability in the CYP450 genes involved in the synthesis of eicosanoids from AA
      may have a significant impact on graft function and survival in renal
      transplantation.

PMID- 26214068
TI  - Anaphylaxis and ethnicity: higher incidence in British South Asians.
AB  - BACKGROUND: The incidence of anaphylaxis in South Asians (Indian, Pakistani and
      Bangladeshi ethnicity) is unknown. Birmingham is a British city with a
      disproportionately large population of South Asians (22.5%) compared with the
      rest of the UK (4.9%). The main aims of this study were to determine the
      incidence and severity of anaphylaxis in this population and to investigate the
      differences between the South Asian and White populations. METHODS: A
      retrospective electronic search of emergency department attendances at three
      hospitals in Birmingham during 2012 was carried out. Wide search terms were used,
      medical notes were scrutinized, and the World Allergy Organization diagnostic
      criteria for anaphylaxis were applied. Patients' age, sex, ethnicity and home
      postal code were collected, reactions were graded by severity, and other relevant
      details including specialist assessment were extracted. Multivariate analysis was
      undertaken using 2011 UK census data. RESULTS: Age-, sex- and ethnicity
      standardized incidence rate of anaphylaxis was 34.5 per 100 000 person-years.
      Multivariate logistic regression which controlled for the confounders of age, sex
      and level of socioeconomic deprivation showed that incidence was higher in the
      South Asian population (OR 1.48, P = 0.005). Incidence rate in the South Asian
      population was 58.3 cases per 100 000 person-years compared to 31.5 in the White
      population. South Asian children were more likely to present with severe
      anaphylaxis (OR 5.31, P = 0.002). CONCLUSIONS: Incidence of anaphylaxis is
      significantly higher in British South Asians compared to the white population.
      British South Asian children are at a greater risk of severe anaphylaxis than
      White children.

PMID- 26214069
TI  - Risk factors for DSM-5 posttraumatic stress symptoms (PTSS) among Israeli
      civilians during the 2014 Israel-Hamas war.
AB  - In light of current modifications in the 5th edition of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for
      posttraumatic stress disorder (PTSD), this study aimed to revalidate well-known
      PTSD risk factors related to terrorism and war in Israel, namely, proximity to
      the Gaza Strip, dissociative symptoms, acute stress disorder (ASD) symptoms, and
      social support. One hundred and sixty Israeli civilians were assessed during the
      2014 Israel-Hamas war at 2 time points: 1 week after the beginning of the
      operation (t1) and 1 month after initial evaluation (t2), using the DSM-5 PTSD
      Symptom Levels Scale (PSLS; Gil, Weinberg, Or-Chen, & Harel, 2015). A paired t
      test analysis showed significant reduction in the respondents' posttraumatic
      stress symptoms (PTSS) 1 month after the initial assessment point. A structural
      equation model (SEM) showed that higher ASD symptoms at t1 and higher
      dissociative symptoms at t2 increased the risk for PTSS at t2. Conversely, higher
      peritraumatic dissociation at t1 decreased the risk for PTSS at t2. Proximity to
      the Gaza Strip, and social support, failed to demonstrate significant association
      with PTSS at t2. DSM-5 PTSS 1 month after prolonged traumatic exposure are
      strongly associated with high ASD symptoms at 1 week as a risk factor; high
      levels of peritraumatic dissociation at 1 week as a protective factor; and high
      levels of dissociative symptoms at 1 month as a risk factor. Theoretically and
      clinically the findings of the study further suggest that ongoing massive
      terrorism and war cannot be viewed or treated as identical to other traumas.

PMID- 26214070
TI  - Shattering world assumptions: A prospective view of the impact of adverse events
      on world assumptions.
AB  - Shattered Assumptions theory (Janoff-Bulman, 1992) posits that experiencing a
      traumatic event has the potential to diminish the degree of optimism in the
      assumptions of the world (assumptive world), which could lead to the development
      of posttraumatic stress disorder. Prior research assessed the assumptive world
      with a measure that was recently reported to have poor psychometric properties
      (Kaler et al., 2008). The current study had 3 aims: (a) to assess the
      psychometric properties of a recently developed measure of the assumptive world,
      (b) to retrospectively examine how prior adverse events affected the optimism of
      the assumptive world, and (c) to measure the impact of an intervening adverse
      event. An 8-week prospective design with a college sample (N = 882 at Time 1 and
      N = 511 at Time 2) was used to assess the study objectives. We split adverse
      events into those that were objectively or subjectively traumatic in nature. The
      new measure exhibited adequate psychometric properties. The report of a prior
      objective or subjective trauma at Time 1 was related to a less optimistic
      assumptive world. Furthermore, participants who experienced an intervening
      objectively traumatic event evidenced a decrease in optimistic views of the world
      compared with those who did not experience an intervening adverse event. We found
      support for Shattered Assumptions theory retrospectively and prospectively using
      a reliable measure of the assumptive world. We discuss future assessments of the
      measure of the assumptive world and clinical implications to help rebuild the
      assumptive world with current therapies. (PsycINFO Database Record

PMID- 26214071
TI  - Effects of Dietary Supplementation with Brazil Nuts on Microvascular Endothelial
      Function in Hypertensive and Dyslipidemic Patients: A Randomized Crossover
      Placebo-Controlled Trial.
AB  - OBJECTIVE: To investigate the effects of dietary supplementation with GBNs on
      microvascular endothelial function in hypertensive and dyslipidemic patients.
      METHODS: Ninety-one patients of both sexes aged 62.1 +/- 9.3 years received 13
      g/day of GBNs or a placebo for three months with a washout period of one month
      between treatments. Microvascular endothelial function was assessed using LSCI
      coupled with iontophoresis of ACh and PORH. We also used skin video
      capillaroscopy to measure capillary density and recruitment at rest and during
      PORH. Plasma concentrations of NOx were also measured as a marker of nitric oxide
      bioavailability. RESULTS: Supplementation with GBNs significantly increased the
      plasma levels of Se (p < 0.05) and NOx (p < 0.05). However, we did not observe
      any effects of GBN consumption on microvascular vasodilator responses to ACh or
      PORH (p > 0.05), and GBNs did not improve capillary density at baseline or
      recruitment during PORH (p > 0.05). CONCLUSIONS: Supplementation with GBNs
      induced significant increases in the plasma Se concentration and systemic
      bioavailability of nitric oxide. Nevertheless, GBN supplementation did not lead
      to any improvement in systemic microvascular reactivity or density in patients
      with arterial hypertension and dyslipidemia who were undergoing multiple drug
      therapies.

PMID- 26214072
TI  - Multienzyme Inkjet Printed 2D Arrays.
AB  - The use of printing to produce 2D arrays is well established, and should be
      relatively facile to adapt for the purpose of printing biomaterials; however,
      very few studies have been published using enzyme solutions as inks. Among the
      printing technologies, inkjet printing is highly suitable for printing
      biomaterials and specifically enzymes, as it offers many advantages. Formulation
      of the inkjet inks is relatively simple and can be adjusted to a variety of
      biomaterials, while providing nonharmful environment to the enzymes. Here we
      demonstrate the applicability of inkjet printing for patterning multiple enzymes
      in a predefined array in a very straightforward, noncontact method. Specifically,
      various arrays of the enzymes glucose oxidase (GOx), invertase (INV) and
      horseradish peroxidase (HP) were printed on aminated glass surfaces, followed by
      immobilization using glutardialdehyde after printing. Scanning electrochemical
      microscopy (SECM) was used for imaging the printed patterns and to ascertain the
      enzyme activity. The successful formation of 2D arrays consisting of enzymes was
      explored as a means of developing the first surface confined enzyme based logic
      gates. Principally, XOR and AND gates, each consisting of two enzymes as the
      Boolean operators, were assembled, and their operation was studied by SECM. 

PMID- 26214073
TI  - Evidence for a zwitterionic transition state in double bond rotations within
      tungsten-vinyl complexes.
AB  - The trianionic pincer supported tungsten-vinyl complex [CF3
      ONO]W(O){(CH3)3CC[double bond, length as m-dash]C(CH3)2} (3syn) undergoes facile
      double bond rotation at ambient temperature. The degenerate methyl exchange rates
      were measured via selective inversion-recovery experiments. DFT computations in
      conjunction with experimentally determined rate constants support a double bond
      rotation that proceeds via a Zwiterionic transition state. 

PMID- 26214074
TI  - Understanding action control of parental support behavior for child physical
      activity.
AB  - OBJECTIVE: Parental support is the critical family-level variable linked to child
      physical activity (PA), yet the antecedents of support are poorly understood, and
      its relationship with intention is modest. The purpose of this study was to apply
      a framework designed to evaluate the intention-behavior gap, known as
      multiprocess action control (M-PAC), to understand parental support for regular
      child PA. METHOD: Mothers (N = 1,253) with children 5-12 years of age completed
      measures of attitudes, perceived control over support, behavioral regulation
      tactics (e.g., planning, self-monitoring), and intention to support. Over half
      (58%) reported on subsequent support behaviors 6 months later. RESULTS: Three
      intention-behavior profiles emerged: (a) nonintenders (26.4%; n = 331), (b)
      unsuccessful intenders (36.6%; n = 458), and (c) successful intenders (33%; n =
      414). Congruent with M-PAC, a discriminant function analysis showed that
      affective attitude about support (r = .18), perceived behavioral control over
      support (r = .55), and behavioral regulation (r = .55) distinguished between all
      3 intention-behavior profiles. A disaggregated analysis of specific behavioral
      regulation tactics showed that most distinguished all 3 profiles, yet planning,
      information seeking, and monitoring were the critical correlates of the
      discriminant function. CONCLUSION: The majority of mothers had positive
      intentions to support regular child PA, yet over half failed to enact this
      support. Difficulty of intention translating into support behavior arises from
      compromised control over support, self-regulation skills, and perceptions that
      the support experience is unenjoyable. Interventions aimed at strengthening these
      factors are recommended to improve parental support action control.

PMID- 26214075
TI  - "Priming" hand hygiene compliance in clinical environments.
AB  - INTRODUCTION: Effective hand hygiene is the single most important procedure in
      preventing hospital-acquired infections. Traditional information/education-based
      interventions have shown only modest benefits on compliance. This study set out
      to investigate whether priming via olfactory and visual cues influences hand
      hygiene compliance. METHOD: Randomized controlled trial set in a surgical
      intensive care unit (SICU) at a teaching hospital in Miami, Florida. The primary
      outcome data involved observations-a mix of health professionals and service
      users were observed entering the SICU by 2 trained observers and their hand
      hygiene compliance was independently verified. Interventions included either an
      olfactory prime (clean, citrus smell) or visual prime (male or female eyes). The
      primary outcome measure was hand hygiene compliance (HHC) measured by the visitor
      using the hand gel dispenser. RESULTS: At a 5% level there was significant
      evidence that a clean, citrus smell significantly improves HHC (46.9% vs. 15.0%,
      p = .0001). Compared to the control group, a significant improvement in HHC was
      seen when a picture of "male eyes" was placed over the hand gel dispenser (33.3%
      vs. 15.0%, p < .038). No significant improvement in HHC was seen when a picture
      of female eyes was placed over the same hand gel dispenser (10.0% vs. 15.0%, p =
      .626). CONCLUSIONS: This is one of the first studies to demonstrate that priming
      can influence HHC in a clinical setting. The findings suggest that priming
      interventions could be used to change other behaviors relevant to public health.

PMID- 26214077
TI  - Correction to Daly, Boyce, and Wood (2014).

PMID- 26214076
TI  - Mediation and moderation of an efficacious theory-based abstinence-only
      intervention for African American adolescents.
AB  - OBJECTIVE: This secondary data analysis sought to determine what mediated
      reductions in self-reported sexual initiation over the 24-month postintervention
      period in early adolescents who received "Promoting Health among Teens," a theory
      based, abstinence-only intervention (Jemmott, Jemmott, & Fong, 2010). METHOD:
      African American Grade 6 and 7 students at inner-city public middle schools were
      randomized to 1 of 5 interventions grounded in social-cognitive theory and the
      theory of reasoned action: 8-hr abstinence-only targeting reduced sexual
      intercourse; 8-hr safer-sex-only targeting increased condom use; 8-hr and 12-hr
      comprehensive interventions targeting sexual intercourse and condom use; 8-hr
      control intervention targeting physical activity and diet. Primary outcome was
      self-report of vaginal intercourse by 24 months postintervention. Potential
      mediators, assessed immediately postintervention, were theory-of-reasoned-action
      variables, including behavioral beliefs about positive consequences of abstinence
      and negative consequences of sex, intention to have sex, normative beliefs about
      sex, and HIV and sexually transmitted infection (STI) knowledge. We tested single
      and serial mediation models using the product-of-coefficients approach. RESULTS:
      Of 509 students reporting never having vaginal intercourse at baseline (324 girls
      and 185 boys; mean age = 11.8 years, SD = 0.8), 500 or 98.2% were included in
      serial mediation analyses. Consistent with the theory of reasoned action, the
      abstinence-only intervention increased positive behavioral beliefs about
      abstinence, which reduced intention to have sex, which in turn reduced sexual
      initiation. Negative behavioral beliefs about sex, normative beliefs about sex,
      and HIV/STI knowledge were not mediators. CONCLUSIONS: Abstinence-only
      interventions should stress the gains to be realized from abstinence rather than
      the deleterious consequences of sexual involvement.

PMID- 26214078
TI  - Permanently densified SiO2 glasses: a structural approach.
AB  - Densified silica can be obtained by different pressure and temperature paths and
      for different stress conditions, hydrostatic or including shear. The density is
      usually the macroscopic parameter used to characterize the different compressed
      silica samples. The aim of our present study is to compare structural
      modifications for silica glass, densified from several routes. For this,
      densified silica glasses are prepared from cold and high temperature (up to 1020 
      degrees C) compressions. The different densified glasses obtained in our study
      are characterized by micro-Raman spectroscopy. Intertetrahedral angles from the
      main band relative to the bending mode decrease and their values are larger for
      densified samples from high temperature compression than those samples from cold
      compression. The relative amount of 3-membered rings deduced from the D2 line
      area increases as a function of density for cold compression. The temperature
      increase during the compression process induces a decrease of the 3 fold ring
      population. Moreover, 3 fold rings are more deformed and stressed for densified
      samples at room temperature at the expense of those densified at high
      temperature. Temperature plays a main role in the reorganization structure during
      the densification and leads to obtaining a more relaxed structure with lower
      stresses than glasses densified from cold compression. The role of hydrostatic or
      non-hydrostatic applied stresses on the glass structure is discussed. From the
      Sen and Thorpe central force model, intertetrahedral angle average value and
      their distribution are estimated. 

PMID- 26214079
TI  - Chemical Force Spectroscopy Evidence Supporting the Layer-by-Layer Model of
      Organic Matter Binding to Iron (oxy)Hydroxide Mineral Surfaces.
AB  - The adsorption of dissolved organic matter (DOM) to metal (oxy)hydroxide mineral
      surfaces is a critical step for C sequestration in soils. Although equilibrium
      studies have described some of the factors controlling this process, the
      molecular-scale description of the adsorption process has been more limited.
      Chemical force spectroscopy revealed differing adhesion strengths of DOM
      extracted from three soils and a reference peat soil material to an iron
      (oxy)hydroxide mineral surface. The DOM was characterized using ultrahigh
      resolution negative ion mode electrospray ionization Fourier Transform ion
      cyclotron resonance mass spectrometry. The results indicate that carboxyl-rich
      aromatic and N-containing aliphatic molecules of DOM are correlated with high
      adhesion forces. Increasing molecular mass was shown to decrease the adhesion
      force between the mineral surface and the DOM. Kendrick mass defect analysis
      suggests that mechanisms involving two carboxyl groups result in the most stable
      bond to the mineral surface. We conceptualize these results using a layer-by
      layer "onion" model of organic matter stabilization on soil mineral surfaces.

PMID- 26214080
TI  - A detailed study of cholinium chloride and levulinic acid deep eutectic solvent
      system for CO2 capture via experimental and molecular simulation approaches.
AB  - Choline chloride + levulinic acid deep eutectic solvent is studied as a suitable
      material for CO2 capturing purposes. The most relevant physicochemical properties
      of this solvent are reported together with the CO2 solubility as a function of
      temperature. The corrosivity of this solvent is studied showing better
      performance than amine-based solvents. A theoretical study using both density
      functional theory and molecular dynamics approaches is carried out to analyze the
      properties of this fluid from the nanoscopic viewpoint, and their relationship
      with the macroscopic behavior of the system and its ability for CO2 capturing.
      The behavior of the liquid-gas interface is also studied and its role on the CO2
      absorption mechanism is analyzed. The reported combined experimental and
      theoretical approach leads to a complete picture of the behavior of this new
      sorbent with regard to CO2, which together with its low cost, and the suitable
      environmental and toxicological properties of this solvent, lead to a promising
      candidate for CO2 capturing technological applications. 

PMID- 26214081
TI  - Meniere's Syndrome or Disease: Time Trends in Management and Quality of Evidence
      Over the Last Two Decades.
AB  - OBJECTIVE: To evaluate the evidence and trends in published literature on the
      treatment of Meniere's syndrome or disease (MS/D) by comparing studies published
      in the last two decades. DATA SOURCES: A literature search was performed on AMED,
      EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH BUSINESS ELITE, CENTRAL and
      Cochrane Ear, Nose and Throat disorders groups trials register using a
      combination of MeSH. The date of last search was October 2014. STUDY SELECTION
      AND DATA EXTRACTION: Two hundred five studies (104 in decade I and 101 in decade
      II) were evaluated to report trends in the management of this condition, the
      differing levels of evidence published for each treatment modality, evaluate
      whether the guidelines published by the AAOHNS-Committee on Hearing and
      Equilibrium had been correctly employed, and whether the randomized controlled
      trials (RCTs) were compliant with the CONSORT guidelines. RESULTS: The number of
      published RCTs almost tripled from decade I (1994-2003) to decade II (2004-2103).
      There was a significant decline in the use of surgical intervention (p = 0.013);
      however, the number of studies involving the use of intratympanic injection
      remained largely unchanged. There was a shift in the level of evidence in
      published studies; studies with level 1 evidence tripled from decade I to II (4.8
      to 17.8%, respectively) (p = 0.03); however, compliance with the AAOHNS-CHE
      criteria for reporting treatment outcomes and the CONSORT checklist was still
      poor. CONCLUSION: Although the evidence base on published literature on MS/D has
      improved over the last decade with an increase in emphasis on RCTs and quality of
      life (QoL) studies, a significant number of studies failed to follow AAOHNS-CHE
      criteria for reporting treatment outcome and the CONSORT criteria for reporting
      RCTs.

PMID- 26214082
TI  - Long-term survival with paclitaxel and gemcitabine for germ cell tumors after
      progression following high-dose chemotherapy with tandem transplant.
AB  - OBJECTIVES: Germ cell tumor patients progressing after high-dose chemotherapy
      (HDCT) have a dismal prognosis. A prior retrospective study of paclitaxel and
      gemcitabine enrolled 32 patients. All failed first-line chemotherapy and salvage
      therapy with HDCT. We now present long-term results. METHODS: Eligible patients
      received BEP or similar first-line chemotherapy and subsequent HDCT. They were
      treated with paclitaxel (100 mg/m) on days 1, 8, and 15 and gemcitabine (1000
      mg/m) on days 1, 8, and 15 every 4 weeks for a maximum of 6 cycles. RESULTS: Ten
      of 32 (31%) had an objective response (4 partial remissions and 6 complete
      responses). Four patients (12.5% of total) have enjoyed long-term survival; 3 are
      continuously disease free for 64, 94, and 122 months. None of these 3 received
      subsequent chemotherapy or surgery. A fourth patient relapsed after 72 months,
      and has now reachieved remission for 36+ months after treatment with the same
      regimen. These patients had 2, 2, 2, and 4 prior therapies, respectively, and a
      rising serum human chorionic gonadotropin (69 and 138 mIU/mL), alpha-fetoprotein
      (525 ng/mL), or increasing intrathoracic metastases. Longest prior response
      ranged from 5 to 24 months. CONCLUSIONS: Paclitaxel and gemcitabine salvage
      chemotherapy can offer long-term survival and probable cure in
      relapsed/refractory germ cell tumor patients after HDCT. This is an appropriate
      regimen in a taxane-naive and gemcitabine-naive patient population. This is the
      first example of a nonplatinum curative chemotherapy regimen in patients
      progressing after HDCT.

PMID- 26214083
TI  - Prognostic significance of Ki67 expression in malignant peritoneal mesothelioma.
AB  - OBJECTIVES: Although Ki67 measurement by immunohistochemistry has been widely
      used as a prognostic index in cancers, it has not been reported in malignant
      peritoneal mesothelioma (MPM). Hence, this study examines the prognostic
      significance of Ki67 in MPM. METHODS: Specimens from 42 MPM patients were
      screened for Ki67 expression using immunohistochemistry. Ki67 expression was
      classified into 2 groups on the basis of expression (<25%=low; >=25%=high) using
      standard methods. Using Kaplan-Meier survival analysis, the significance of Ki67
      was assessed in different clinicopathologic categories. RESULTS: High expression
      of Ki67 (>=25% by immunohistochemical evaluation) was correlated with poor
      survival in the overall group (P=0.001); male sex (P=0.001); female sex
      (P=0.001); epithelioid tumors (P=0.001): male epithelioid (P=0.001), female
      epithelioid (P=0.003); peritoneal cancer index (PCI): PCI<20 (P=0.001), PCI>=20
      (P=0.002); and age at diagnosis (AAD): AAD<60 years (P=0.001), AAD>=60 years
      (P=0.004). Independent of Ki67, male sex (P=0.007), sarcomatoid histology
      (P=0.001), PCI>=20 (P=0.013), and AAD>=60 years (P=0.004) correlated with poor
      survival. Multivariate analysis showed that only AAD>=60 years (P=0.049) and high
      Ki67 expression for all tumors (P=0.031), male sex (P=0.038), female sex
      (P=0.021), epithelioid tumors (P=0.044), and AAD<60 years (P=0.029) were
      statistically significant. CONCLUSIONS: Ki67 expression affects prognosis in MPM
      patients and helps to predict survival within the various clinicopathologic
      categories.

PMID- 26214084
TI  - Results of a phase II study of Short-course Accelerated Radiation Therapy
      (SHARON) for multiple brain metastases.
AB  - OBJECTIVES: To assess the effectiveness of a SHort-course Accelerated RadiatiON
      therapy (SHARON) in the treatment of patients with multiple brain metastases.
      MATERIALS AND METHODS: A phase II clinical trial was designed. Eligibility
      criteria included patients with at least 3 brain metastases or metastatic disease
      in >3 organ systems, and Eastern Cooperative Oncology Group performance status of
      <=3. Fifty patients were treated with whole brain radiotherapy at 18 Gy (4.5 Gy
      per fraction) in 2 days with a twice daily fractionation. The primary endpoint
      was the assessment of efficacy in terms of overall survival. RESULTS:
      Characteristics of the 50 enrolled patients were: male/female: 24/26; median age:
      65 years (range, 45 to 80 y). Eastern Cooperative Oncology Group performance
      status was <3 in 42 patients (84%). Nineteen patients (38%) were considered to
      have recursive partitioning analysis class 3 disease. Grade 1-2 acute
      neurological (46%) and skin (24%) toxicities were recorded. Three patients (6%)
      experienced neurological grade 3 acute toxicity. With a median follow-up time of
      6 months (range, 1 to 18 mo) 2 skin grade 1 late toxicities has been observed.
      Seventeen of 27 symptomatic patients showed an improvement or resolution of
      baseline symptoms (overall palliative response rate: 63.0%; 95% confidence
      interval, 36.6%-82.4%).Two-month overall survival was 86% (median survival time=7
      mo). CONCLUSIONS: Short-course accelerated whole brain radiotherapy of 18 Gy in
      twice daily fractions for 2 consecutive days is tolerated and effective in terms
      of symptom relief and median survival time. These results justify a phase III
      comparison against the standard-of-care in this patient population (30 Gy in 10
      fractions).

PMID- 26214085
TI  - Phase I and pharmacokinetic study of erlotinib administered in combination with
      amrubicin in patients with previously treated, advanced non-small cell lung
      cancer.
AB  - OBJECTIVES: We conducted a phase I trial of erlotinib, an epidermal growth factor
      receptor tyrosine kinase inhibitor, combined with amrubicin, a topoisomerase II
      inhibitor. The aim was to determine the maximum tolerated dose, the dose-limiting
      toxicities (DLTs), and the pharmacokinetics of this combination in patients with
      non-small cell lung cancer who had received previous chemotherapy. METHODS: A
      total of 9 patients with stage IV disease were treated at 3-week intervals with
      erlotinib once daily on days 1 through 21 plus a 5-minute intravenous injection
      of amrubicin on days 1 through 3. RESULTS: The dose levels evaluated were
      erlotinib (mg/body)/amrubicin (mg/m): 100/30 (n=3), 100/35 (n=3), and 150/30
      (n=3). The maximum tolerated dose of erlotinib and amrubicin was 100 mg/body and
      35 mg/m because 2 of the 3 patients experienced DLTs during the first cycle of
      treatment at the third dose level of 150 mg/body and 30 mg/m. Cessation of
      erlotinib administration for 8 days because of grade 3 leukopenia and grade 3
      skin infection (erysipelas) were the DLTs. No drug-drug interactions between
      erlotinib and amrubicin were observed in this study. The overall response rate
      was 33%, including 3 partial responses, in the 9 patients. The median progression
      free survival for all patients was quite long, 11.3 months, and the median
      overall survival has not yet been reached. CONCLUSIONS: Combined erlotinib plus
      amrubicin therapy seems to be highly effective, with acceptable toxicity, against
      non-small cell lung cancer. The recommended dose for phase II studies was
      erlotinib 100 mg once daily on days 1 through 21, and amrubicin 35 mg/m on days 1
      through 3 administered every 21 days.

PMID- 26214086
TI  - Development of Dural Arteriovenous Fistulas After Cerebral Venous Sinus
      Thrombosis.
AB  - A 57-year-old man presented with papilledema due to partially recanalized dural
      sinus thrombosis and was treated with anticoagulation and acetazolamide. One year
      after treatment and resolution of his symptoms, he had an increase in his optic
      disc edema accompanied by headaches. Subsequent neuroimaging indicated
      development of arteriovenous fistulas resulting in cortical and deep venous
      reflux. Given the high risk of mortality from intracranial hemorrhage, the
      patient underwent urgent treatment with a liquid embolic agent, which resulted in
      the resolution of his optic disc edema. Our case is unique in that recurrence of
      bilateral optic disc edema led to discovery of the rare complication of dural
      arteriovenous fistulas developing after dural sinus thrombosis. Ongoing
      monitoring of patients after cerebral venous sinus thrombosis is, therefore,
      important. 

PMID- 26214087
TI  - Out of control: A self-control perspective on the link between surface acting and
      abusive supervision.
AB  - In this study, we examined how leaders' customer interactions influence their
      tendency to abuse their followers. Specifically, we drew from ego-depletion
      theory to suggest that surface acting during customer interactions depletes
      leaders of their self-control resources, resulting in elevated levels of abusive
      supervision. Furthermore, we hypothesized that the effect of surface acting on
      abusive supervision is moderated by leaders' trait self-control, such that
      leaders with high trait self-control will be less affected by the depleting
      effects of surface acting than their peers. Results from a multiwave, multisource
      leader-follower dyad study in the service and sales industries provided support
      for our hypotheses. This research contributes to several literatures,
      particularly to an emerging area of study--the antecedents of leaders' abusive
      behaviors.

PMID- 26214088
TI  - The lives of others: Third parties' responses to others' injustice.
AB  - This research takes a moral perspective to studying third parties' reactions to
      injustice as a function of their moral identity. Drawing from theories of deontic
      justice, moral intuition, moral heuristics, and moral identity, we develop and
      test a model of the moral underpinnings of third parties' reactions to injustice.
      First, we compare third parties' responses with interpersonal, distributive, and
      procedural justice violations. We hypothesize that third parties are more likely
      to intuit that interpersonal justice violations are morally wrong, compared with
      distributive and procedural justice violations. As a result, third parties are
      more likely to experience stronger moral anger and punish violators in response
      to interpersonal transgressions compared with distributive and procedural justice
      transgressions. Second, we test the proposition that third parties with a strong
      moral identity will react more strongly to justice violations than third parties
      with a comparatively weak moral identity. Results from 3 studies support these
      predictions.

PMID- 26214089
TI  - Healthy volunteer effect in a lung cancer screening study.

PMID- 26214091
TI  - Finasteride for postmenopausal breast cancer prevention.

PMID- 26214090
TI  - 'Diagnostic radiography and thyroid cancer' - causation or simply an association?

PMID- 26214092
TI  - 1,4-Functionalization of 1,3-dienes with low-valent iron catalysts.
AB  - Iron-catalyzed or -mediated transformations of organic substrates have been
      important throughout the development of organic chemistry due to iron's
      abundance, low cost, and favorable toxicity profile. Highly reduced iron species,
      although difficult to isolate and characterize, have proven valuable as catalysts
      for a variety of C-C and C-heteroatom bond forming processes, as well as
      cyclization and cycloisomerization reactions. We have developed iminopyridine
      ligated low-valent iron catalysts that facilitate selective 1,4-hydrovinylation,
      hydoboration, hydrosilylation, and polymerization of 1,3-dienes. The catalysts
      are generated in situ from iron(II) precursors in the presence of activated
      magnesium metal or trialkylaluminum reductants. The 1,4-addition processes
      provide access to valuable products such as 1,4-dienes, allylboronic esters,
      allylsilanes, and highly regioregular polyisoprene. In these transformations,
      addition is stereoselective, providing (E)-alkene isomers selectively, and (1,2)
      addition products are generally not observed. Moreover, modification of steric
      bulk on the iminopyridine ligand can be used to change selectivity for (1,4)-
      versus (4,1)-addition to dienes with nonsymmetric substitution. Access to low
      valent iron precursor complexes is limited, and we have developed a
      diaryliron(II) precursor that undergoes smooth reductive elimination in the
      presence of iminopyridine ligands to provide easy access to low-valent iron
      catalysts without the use of heterogeneous reductants, which complicate the
      isolation and study of low-valent iron complexes. We obtained crystal structures
      of our iron(II) catalyst precursor and an iminopyridine-ligated reduced iron
      species generated from it. Spectroscopic analysis suggests that although this
      species is formally iron(0), the redox-active iminopyridine ligands accept
      electron density from the metal and the complex is more properly formulated as
      iron(II) coordinated by two radical-anion ligands. We believe that a closely
      related set of reaction manifolds is responsible for the 1,4-functionalization
      reactivity displayed by the iron(iminopyridine) complexes (see text). Kinetics
      experiments and deuterium-labeling studies provide evidence for the proposed
      catalytic cycle. The geometry of the double bond remaining after 1,4-addition is
      set by the requirement that the diene bind to the iron center in an s-cis
      geometry, and the regioselectivity of addition can be rationalized by the
      location of steric bulk on the iminopyridine ligand. The transformations
      presented in this Account utilize iron catalysts to provide access to valuable
      diene 1,4-addition products such as 1,4-dienes, allylboronate esters, and
      allylsilanes, as well as highly regioregular polyisoprene. The development of a
      stable diaryliron(II) precatalyst, structural characterization of an
      iminopyridine-ligated iron(0) complex, and mechanistic insights into the
      selective nature of this transformation provide a window into the reactivity
      profile of low-valent iron. 

PMID- 26214093
TI  - Comparison of different counting chambers using a computer-assisted semen
      analyzer.
AB  - A routine computer-assisted sperm analysis is an important diagnostic test in the
      andrology laboratory. To evaluate the accuracy and precision of the different
      types of counting chambers for human semen analysis in combination with a
      computer-assisted semen analyzer (CASA), a quality-control study that compared
      human sperm analysis results obtained using different counting chambers (Makler
      chamber, disposable 8-cell GoldCyto chamber, disposable 4-cell Leja chamber, a
      plain glass slide, and a tissue culture dish cover with a 24 * 24 mm(2)
      coverslip) in conjunction with the CASA systems was performed. Significantly
      higher counts of sperm concentration were obtained from the reusable Makler
      chamber than from the other counting chambers. Sperm motility from drop loaded
      counting chambers was significantly higher than that of capillary-loaded
      chambers. A plain glass slide and a tissue culture dish cover used with a
      coverslip showed rather better performance in semen assessment. Disposable
      chambers are suitable for routine semen analysis with CASA in a diagnostic
      andrology setting. With the proper workflow and quality control, a plain glass
      slide and the tissue culture dish cover are acceptable alternatives for routine
      counting chambers with CASA as necessary. The type of counting chamber should be
      specified in test reports.

PMID- 26214094
TI  - Concerted Halogen-Bonded Networks with N-Alkyl Ammonium Resorcinarene Bromides:
      From Dimeric Dumbbell to Capsular Architectures.
AB  - N-Alkyl ammonium resorcinarene bromides and 1,4-diiodooctafluorobutane via
      multiple intermolecular halogen bonds (XB) form different exotic supramolecular
      architectures through subtle changes of the upper rim substituents. Dimeric
      dumbbell-like assembly with encapsulated guest molecules is generated with N
      benzyl substituents. The N-hexyl groups engender an XB-induced polymeric
      pseudocapsule and an XB-induced dimeric capsule with entrapped 1,4-dioxane guest
      molecules. The N-propyl and N-cyclohexyl groups generate deep cavity cavitands.
      The deep cavity cavitands possess cavities for self-inclusion leading to
      polymeric herringbone arrangement in one direction and that pack into 3D
      polymeric arrangement resembling egg crate-like supramolecular networks. These
      assemblies are studied in solution via NMR spectroscopy and in the solid state
      via X-ray crystallography. 

PMID- 26214096
TI  - Posttraumatic stress, effort regulation, and academic outcomes among college
      students: A longitudinal study.
AB  - Entering college with posttraumatic stress disorder (PTSD) symptomatology has
      been linked to poor academic performance and increased risk for dropping out of
      college; however, little is known regarding the mechanisms by which PTSD symptoms
      have deleterious effects on college outcomes. Drawing from a self-regulated
      learning (SRL) perspective, which suggests that students' learning behaviors and
      outcomes can be influenced by contextual and developmental factors, we
      hypothesized that students who enter college with high PTSD symptomatology may
      experience difficulties in effort regulation, which in turn, may have deleterious
      effects on their academic performance and college persistence. These hypothesized
      relationships, as well as the potential gender differences in these relationships
      were examined using a longitudinal study design and a multigroup structural
      equation modeling approach. Of the 928 1st-year students who participated in the
      study, 484 (52.2%) students who reported lifetime exposure to traumatic events
      constituted the final sample of the study. The prevalence of PTSD among the
      trauma-exposed participants was 12.4%. After controlling for participation in on
      campus activities and American College Testing (ACT) assessment scores, the
      relationship between PTSD symptomatology in the 1st semester of college and 2nd
      year enrollment was mediated by effort regulation and 1st-year cumulative grade
      point average (GPA). Specifically, participants who started college with higher
      levels of PTSD symptomatology also reported lower levels of effort regulation,
      which in turn, had a significant indirect effect on 2nd-year enrollment through
      1st-year GPA. Results also indicated that the paths in the hypothesized model
      were not significantly different for men and women. (PsycINFO Database Record 

PMID- 26214095
TI  - Human saliva as route of inter-human infection for mouse mammary tumor virus.
AB  - Etiology of human breast cancer is unknown, whereas the Mouse Mammary Tumor Virus
      (MMTV) is recognized as the etiologic agent of mouse mammary carcinoma. Moreover,
      this experimental model contributed substantially to our understanding of many
      biological aspects of the human disease. Several data strongly suggest a
      causative role of MMTV in humans, such as the presence of viral sequences in a
      high percentage of infiltrating breast carcinoma and in its preinvasive lesions,
      the production of viral particles in primary cultures of breast cancer, the
      ability of the virus to infect cells in culture. This paper demonstrates that
      MMTV is present in human saliva and salivary glands. MMTV presence was
      investigated by fluorescent PCR, RT-PCR, FISH, immunohistochemistry, and whole
      transcriptome analysis. Saliva was obtained from newborns, children, adults, and
      breast cancer patients. The saliva of newborns is MMTV-free, whereas MMTV is
      present in saliva of children (26.66%), healthy adults (10.60%), and breast
      cancer patients (57.14% as DNA and 33.9% as RNA). MMTV is also present in 8.10%
      of salivary glands. RNA-seq analysis performed on saliva of a breast cancer
      patient demonstrates a high expression of MMTV RNA in comparison to negative
      controls. The possibility of a contamination by murine DNA was excluded by murine
      mtDNA and IAP LTR PCR. These findings confirm the presence of MMTV in humans,
      strongly suggest saliva as route in inter-human infection, and support the
      hypothesis of a viral origin for human breast carcinoma. 

PMID- 26214097
TI  - Personality Structure Among Centenarians: The Georgia Centenarian Study.
AB  - BACKGROUND/STUDY CONTEXT: We demonstrate that observer-rated factor structure of
      personality in centenarians is congruent with the normative structure. Prevalence
      of cognitive impairment, which has previously been linked to changes in
      personality in younger samples, is high in this age group, requiring observer
      ratings to obtain valid data in a population-based context. Likewise, the broad
      range of cognitive functioning necessitates synthesis of results across multiple
      measures of cognitive performance. METHODS AND RESULTS: Data from 161
      participants in the Georgia Centenarian Study (GCS; MAge = 100.3 years, 84%
      women, 20% African American, 40% community-dwelling, 30% low cognitive
      functioning) support strong overall correspondence with reference structure (full
      sample: .94; higher cognitive functioning: .94; lower cognitive functioning:
      .90). Centenarians with lower cognitive functioning are higher on neuroticism and
      lower on openness to experience, agreeableness, and conscientiousness. Facet
      level differences (higher N1-N6: anxiety, hostility, depression, self
      consciousness, impulsiveness, vulnerability to stress; lower E1: warmth; lower O4
      O6: actions, ideas, values; lower A1, A3, A4: trust, altruism, compliance; C1,
      C5: competence, self-discipline) are also observed. Multivariate factor-level
      models indicate only neuroticism of the five broad factors predicts membership in
      cognitively impaired group; facet-level models showed that lower-order scales
      from three of the five domains were significant. Centenarians with higher self
      consciousness (N4), impulsiveness (N5), and deliberation (C6) but lower ideas
      (O5), compliance (A4), and self-discipline (C5) were more likely to be in the
      lower cognitive functioning category. CONCLUSION: Results present first normative
      population-based data for personality structure in centenarians and offer
      intriguing possibilities for the role of personality in cognitive impairment
      centered on neuroticism.

PMID- 26214098
TI  - Normative Data for the Cognitively Intact Oldest-Old: The Framingham Heart Study.
AB  - BACKGROUND/STUDY CONTEXT: The number of individuals who reach extreme age is
      quickly increasing. Much of the current literature focuses on impaired cognition
      in extreme age, and debate continues regarding what constitutes "normal"
      cognition in extreme age. This study aimed to provide oldest-old normative data
      and to compare cognitive performances of cognitively intact elderly individuals
      from the Framingham Heart Study. METHODS: A total of 1302 individuals aged 65+
      years from the Framingham Heart Study were separated into 5-year age bands and
      compared on cognitive tests. Multivariate linear regression analyses were
      conducted, adjusting for gender, the Wide Range Achievement Test-Third Edition
      (WRAT-III) Reading score, and cohort. Analyses also included comparisons between
      418 individuals aged 80+ and 884 individuals aged 65-79, and comparisons within
      oldest-old age bands. RESULTS: Normative data for all participants are presented.
      Significant differences were found on most tests between age groups in the
      overall analysis between young-old and oldest-old, and analysis of oldest-old age
      bands also revealed select significant differences (all ps <.05). CONCLUSION: As
      aging increases, significant cognitive differences and increased variability in
      performances are evident. These results support the use of age-appropriate
      normative data for oldest-old individuals.

PMID- 26214099
TI  - Positive Perception of Aging and Performance in a Memory Task: Compensating for
      Stereotype Threat?
AB  - BACKGROUND/STUDY CONTEXT: The aim of this research is to explore whether segments
      of seniors might be immune to aging stereotypes of the older adult group.
      Stereotype threat research indicates that older adults show low memory recall
      under conditions of stereotype threat. Stereotype internalization theory (Levy,
      2009) predicts that a positive perception of aging has favorable effects on the
      behavior and health of older people. METHODS: A total of 112 older adult
      participants (62% women, aged 55 to 78) attending the University Programme for
      Older Adults were assigned to one of two conditions: stereotype threat condition
      and positive information condition. A control group was included from
      participants in the same program (n = 34; 61% women, aged 55 to 78). Individual
      differences in self-perception of aging were considered as continuous variable.
      RESULTS: Participants with better self-perception of aging showed better memory
      performance than those with poorer self-perception of aging in the stereotype
      threat condition and control condition. However, no differences were found in the
      positive information condition between participants with high and low self
      perception of aging. These results indicate that positive self-perception of
      aging moderates the effects of stereotype threat, and that positive information
      promotes better memory performance for those older adults with a poorer self
      perception of aging. CONCLUSION: As expected, individuals with a positive
      perception of their own aging were less vulnerable to the activation of a
      negative older adult stereotype in the stereotype threat condition.

PMID- 26214100
TI  - Naturalistic Assessment of Everyday Memory Performance Among Older Adults.
AB  - BACKGROUND/STUDY CONTEXT: Memory performance in everyday life (EDL) and its
      change through aging is still unclear because laboratory results are often not
      transferable to real-life situations. Therefore, a naturalistic memory task was
      designed to investigate memory performance in older adults in a representative
      task design. METHODS: The memory performance of 23 older (70.28 +/- 4.65 years)
      and 20 younger adults (24.89 +/- 3.16 years) was assessed by using four
      established tasks of short-term and working memory (Digit Simple Span, Digit
      Complex Span, Grid Simple Span, and Grid Complex Span) that differed in
      difficulty and domain (verbal vs. visual-spatial). To simulate an EDL context, a
      "Supermarket" was constructed within the laboratory. RESULTS: The results showed
      that memory performance presents alterations in older adults. This was especially
      true for the "Supermarket" task, in which the younger adults showed benefits in
      the common environment as opposed to older adults. A factor analysis showed that
      the four memory laboratory tasks measured different memory processes as compared
      with the EDL task. CONCLUSION: These findings suggest that memory performance in
      EDL is a different construct than when it is measured in the laboratory and that
      memory alterations in older adults are especially pronounced in EDL tasks.
      Following these findings, the authors recommend an EDL approach to measure memory
      performance further to the well-established laboratory approaches.

PMID- 26214101
TI  - If You Are Old and Do Not Want to Fall into The Traditional Stereotype--Be
      Physically Active!
AB  - BACKGROUND/STUDY CONTEXT: Based on the stereotype content model and the behaviors
      from intergroup affect and stereotypes map (Cuddy et al., 2008; Advances in
      experimental social psychology [Vol. 40, pp. 61-149], New York: Academic Press),
      we examined whether being physically active may challenge the traditional
      stereotypes related to older adults. METHODS: We compared how 94 participants
      (M(age) = 24.48 years, SD = 7.15 years) judged one of three target groups (older
      adults in general, physically active older adults, and socially active older
      adults), with regard to perceived status and competition, warmth and competence
      judgments, emotional and behavioral reactions. RESULTS: Results showed that being
      physically active was associated with higher status and competence. Physically
      active older adults were specifically viewed as an admired group eliciting both
      active (helping) and passive facilitation (associating) tendencies. CONCLUSION:
      Beyond the well-known health perspective related to the regular participation of
      older adults in physical activity, the present results open a social optimistic
      perspective, in which being physically active seems a promising way to challenge
      the widespread and resistant stereotype content of older people commonly
      perpetuated.

PMID- 26214102
TI  - Pain Intensity Moderates the Relationship Between Age and Pain Interference in
      Chronic Orofacial Pain Patients.
AB  - BACKGROUND/STUDY CONTEXT: Chronic pain is associated with increased interference
      in daily functioning that becomes more pronounced as pain intensity increases.
      Based on previous research showing that older adults maintain well-being in the
      face of pain as well as or better than their younger counterparts, the current
      study examined the interaction of age and pain intensity on interference in a
      sample of chronic orofacial pain patients. METHODS: Data were obtained from the
      records of 508 chronic orofacial pain patients being seen for an initial
      evaluation from 2008 to 2012. Collected data included age (range: 18-78) and self
      reported measures of pain intensity and pain interference. Bivariate correlations
      and regression models were used to assess for statistical interactions. RESULTS:
      Regression analyses revealed that pain intensity positively predicted pain
      interference (R(2) = .35, B = 10.40, SE = 0.62, t(507) = 16.70, p < .001). A
      significant interaction supported the primary hypothesis that aging was
      associated with reduced interference at high levels of pain intensity (DeltaR(2)
      = .01, B = -1.31, SE = 0.63, t(505) = -2.90, p = .04). CONCLUSION: At high levels
      of pain intensity, interference decreased with age, although the age by pain
      intensity interaction effect was small. This evidence converges with aging
      theories, including socioemotional selectivity theory, which posits that as
      people age, they become more motivated to maximize positive emotions and minimize
      negative ones. The results highlight the importance of studying the mechanisms
      older adults use to successfully cope with pain.

PMID- 26214103
TI  - Assessing health care in Canada's North: what can we learn from national and
      regional surveys?
AB  - BACKGROUND: Health surveys are a rich source of information on a variety of
      health issues, including health care. OBJECTIVES: This article compares various
      national and regional surveys in terms of their geographical coverage with
      respect to the Canadian North, especially their Aboriginal population, and the
      comparability of the survey contents relating to health care. METHODS: Three
      surveys were selected as providing some information on health care, with separate
      estimates for the North and its Aboriginal populations. They are the Canadian
      Community Health Survey (CCHS), Aboriginal Peoples Survey (APS) and the First
      Nations Regional Health Survey (RHS). RESULTS: Different surveys focus on
      different categories of Aboriginal people, and no single survey has covered all
      categories of Aboriginal people in the North consistently. RHS is targeted at the
      on-reserve First Nations population only. APS and CCHS sample the off-reserve
      First Nations population as well as Metis and Inuit. To achieve adequate sample
      size for North-South comparisons and comparisons among Aboriginal groups within
      the North, several cycles of the biennial/annual CCHS can be merged, producing a
      large data set with consistent coverage of topics using comparable questions. The
      content areas of the 3 surveys can be broadly categorized as health status,
      health determinants and health care. Substantial variation exists across surveys
      in the domains covered. There are also changes over time in terms of definitions,
      questions and even basic concepts. The available health care content of the 3
      surveys focus on access to different types of health services, contact with
      different categories of health professionals, unmet health needs and the use of
      preventive services. Many important dimensions of health care are not covered.
      Not all these basic indicators are available for the North or its Aboriginal
      populations. CONCLUSIONS: A comprehensive survey of health care in the North with
      sufficient sample size to provide reliable estimates for its subpopulations -
      urban and remote, Aboriginal and non-Aboriginal, and First Nations, Inuit and
      Metis - would provide useful information to decision-makers and service
      providers. Analytical studies can also be conducted to investigate the
      correlations and interactions among health status, health determinants and health
      care and assess whether such relationships differ among the different population
      groups.

PMID- 26214104
TI  - Simultaneous assessment of protein heterogeneity and affinity by capillary
      electrophoresis-mass spectrometry.
AB  - Most conventional analytical tools for the assessment of protein-protein
      interactions yield information on the bulk sample. By employing the efficient
      separation of intact proteins, affinity capillary electrophoresis (ACE) can
      measure the interaction of components of heterogeneous proteins with a target
      protein. In this work, the hyphenation of ACE with mass spectrometry (MS) is
      presented as a novel, highly selective tool for the assessment of protein-protein
      interactions. The binding of the protease inhibitor aprotinin to trypsinogen was
      used as protein-protein affinity model. A trypsinogen sample comprising several
      modifications was analyzed using a background electrolyte of 25 mM ammonium
      acetate (pH 8.0) containing increasing concentrations of aprotinin (0-300 MUM). A
      capillary coating of polybrene-dextran sulfate-polybrene (PB-DS-PB) was employed
      to prevent adsorption of the proteins to the capillary wall. The trypsinogen
      variants were separated and could be assigned based on detected molecular masses
      and relative migration. In presence of aprotinin, both free and aprotinin-bound
      trypsinogen were detected revealing a 1:1 binding stoichiometry. For most
      trypsinogen variants, shifts in electrophoretic mobility were observed upon
      raising the aprotinin concentration, allowing determination of their dissociation
      constants (Kd's). The interacting trypsinogen variants showed similar affinity
      toward aprotinin (Kd's of 3-9 MUM), which were not significantly different from
      the values obtained with ACE-UV and were in agreement with an earlier reported
      value. The use of the ratio of obtained MS signal intensities of free and protein
      protein complex for the determination of Kd's was also explored. Derived Kd
      values (20-104 MUM) for the binding variants were similar to those obtained with
      direct-infusion MS, but higher and less precise as compared with values based on
      mobility shifts. The suitability of the ACE-MS methodology for the affinity
      profiling of heterogeneous protein samples was evaluated, and components with
      high, medium, or low affinity toward aprotinin could be successfully
      discriminated. 

PMID- 26214105
TI  - THYROID FUNCTION AND METABOLIC SYNDROME: A CROSS-SECTIONAL STUDY IN OBESE AND
      OVERWEIGHT PATIENTS.
AB  - OBJECTIVE: Metabolic syndrome (MetS) is associated with increased risks of
      developing cardiovascular disease and type 2 diabetes. Thyroid dysfunction is
      also a known cardiovascular risk factor. In obese patients, serum thyroid
      stimulating hormone (TSH) levels tend to be higher than in lean controls. The
      objective of this study was to assess potential associations between serum TSH
      levels and MetS as well as individual components of MetS. METHODS: This was a
      cross-sectional observational study of obese and overweight patients seen for
      initial evaluation at the Boston Medical Center weight-management clinic between
      February 1, 2013 and February 1, 2014. Demographic, anthropometric, and
      laboratory data including serum TSH, insulin, glucose, hemoglobin A1c, and lipid
      levels were obtained from electronic medical records. Associations between serum
      TSH levels and presence of MetS and its components were assessed. RESULTS: A
      total of 3,447 patients, 75.6% female and 38% African American, without known
      thyroid dysfunction, were included. Mean +/- SD age was 46.74 +/- 15.11 years,
      and mean +/- SD body mass index was 36.06 +/- 9.89 kg/m(2). Among 1,005 patients
      without missing data, the prevalence of MetS was 71.84%. In patients with MetS,
      the median serum TSH was 1.41 MUIU/mL, compared with 1.36 MUIU/mL in patients
      without MetS (P = .45). In multivariate models, there was no significant
      association between serum TSH levels and the presence of MetS, adjusting for age,
      sex, race, education, socioeconomic status, and smoking. There were also no
      significant associations between serum TSH and individual components of the MetS.
      CONCLUSION: Serum TSH level does not appear to be a potentially modifiable risk
      factor for MetS in obese and overweight individuals.

PMID- 26214106
TI  - A MUCH-NEEDED HISTORIC PERSPECTIVE ON THE THERAPEUTIC USE OF THYROID HORMONES.

PMID- 26214107
TI  - INSULIN-LIKE GROWTH FACTOR-1 AND ANEMIA IN OLDER SUBJECTS: THE INCHIANTI STUDY.
AB  - OBJECTIVE: Recent studies indicate a role for the age-related decline of anabolic
      hormones, especially testosterone, in the onset of "anemia of aging." Some of
      testosterone's erythropoietic activities are mediated by insulin-like growth
      factor (IGF)-1, which also seems to have independent erythropoietic effects.
      However, the associations among IGF-1, anemia, and hemoglobin (Hb) have not been
      adequately investigated in older populations. METHODS: We used data from a
      representative sample of 953 subjects >=65 years who participated in the
      InCHIANTI (Invecchiare in Chianti) Study and were not on growth hormone (GH) or
      erythropoietin therapy and were not diagnosed with hematologic malignancies or
      other cancers. Anemia was defined according to the World Health Organization
      (WHO) criteria by Hb level <=13 g/dL in males and <=12 g/dL in females. Backward
      multiple regression analyses including age, IGF binding protein (IGFBP)-3,
      testosterone, comorbidities, inflammatory markers, and anemia-related measures
      were used to address the relationship between IGF-1 and Hb and between IGF-1 and
      anemia in both sexes. RESULTS: We found that 46/410 (11.2%) males and 71/543
      (13.0%) females were defined as anemic. After adjustment for age, anemic males
      (100 +/- 54 vs. 130 +/- 56, P<.001) and females (89.1 +/- 48 vs. 110 +/- 52, P =
      .001) exhibited lower IGF-1 levels than their nonanemic counterparts. IGF-1
      levels were independently and negatively associated with anemia in males (beta +/
      SE = -0.0005 +/- 0.0002, P = .04) but not in females (beta +/- SE = -0.0002 +/-
      0.0002, P = .40). In both males (beta +/- SE = 0.002 +/- 0.001, P = .03) and
      females (beta +/- SE = 0.002 +/- 0.0009, P = .03), IGF-1 levels were
      independently and positively associated with Hb levels. CONCLUSION: In older
      males but not in females, IGF-1 levels are negatively associated with anemia. IGF
      1 levels are independent and positive determinants of Hb concentration in both
      sexes.

PMID- 26214109
TI  - MAXIMIZING PATIENT SAFETY WITH NEWLY APPROVED THERAPIES: FOCUS ON SGLT2
      INHIBITORS.

PMID- 26214108
TI  - GLYCATED ALBUMIN AT 4 WEEKS CORRELATES WITH A1C LEVELS AT 12 WEEKS AND REFLECTS
      SHORT-TERM GLUCOSE FLUCTUATIONS.
AB  - OBJECTIVE: Evaluate the performance of glycated albumin (GA) monitoring by
      comparing it to other measures of glycemic control during intensification of
      antidiabetic therapy. METHODS: This 12-week, prospective, multicenter study
      compared the diagnostic clinical performance of GA to glycated hemoglobin A1C
      (A1C), fructosamine corrected for albumin (FRA), fasting plasma glucose (FPG),
      and mean blood glucose (MBG) estimated from self-monitoring of blood glucose
      (SMBG) and continuous glucose monitoring (CGM) in 30 patients with suboptimally
      controlled type 1 or 2 diabetes. RESULTS: Mean A1C decreased from 9.5% to 8.1%.
      Mean SMBG correlated closely with CGM (Pearson r = 0.783 for daily estimates and
      r = 0.746 for weekly estimates, P<.0001). Both GA and FRA levels significantly
      correlated with changes from baseline in A1C and mean weekly SMBG (P<.001). The
      lowest observed median GA occurred at 4 weeks, followed by a small increase and
      then a slight reduction, mirroring changes in overall mean SMBG values. The
      median A1C fell throughout the treatment period, failing to reflect short-term
      changes in SMBG. A >=1% reduction in GA at 4 weeks was significantly associated
      with a >=0.5% change in A1C at 12 weeks (odds ratio [OR] = 19.0, 95% confidence
      interval [CI]: 1.4, 944, P = .018). CONCLUSION: In patients receiving glucose
      lowering therapy, changes in GA at 4 weeks were concordant with changes in A1C at
      12 weeks, and both GA and FRA more accurately reflected short-term blood glucose
      fluctuations than A1C.

PMID- 26214111
TI  - THE SYNERGY TO ENABLE GLYCEMIC CONTROL FOLLOWING EMERGENCY DEPARTMENT DISCHARGE
      PROGRAM FOR ADULTS WITH TYPE 2 DIABETES: STEP-DIABETES.
AB  - OBJECTIVE: To evaluate a diabetes (DM) care delivery model among hyperglycemic
      adults with type 2 DM being discharged from the emergency department (ED) to
      home. The primary hypothesis was that a focused education and medication
      management intervention would lead to a greater short-term improvement in
      glycemic control compared to controls. METHODS: A 4-week, randomized controlled
      trial provided antihyperglycemic medications management using an evidence-based
      algorithm plus survival skills diabetes self-management education (DSME) for ED
      patients with blood glucose (BG) levels >=200 mg/dL. The intervention was
      delivered by endocrinologist-supervised certified diabetes educators. Controls
      received usual ED care. RESULTS: Among 101 participants (96% Black, 54% female,
      62.3% Medicaid and/or Medicare insurance), 77% completed the week 4 visit.
      Glycated hemoglobin A1C (A1C) went from 11.8 +/- 2.4 to 10.5 +/- 1.9% (P<.001)
      and 11.5 +/- 2.0 to 11.1 +/- 2.1% in the intervention and control groups,
      respectively (P = .012). At 4 weeks, the difference in A1C reduction between
      groups was 0.9% (P = .01). Mean BG decreased for both groups (P<.001), with a
      higher percentage of intervention patients (65%) reaching a BG <180 mg/dL
      compared to 29% of controls (P = .002). Hypoglycemia rates did not differ by
      group, and no severe hypoglycemia was reported. Medication adherence (Modified
      Morisky Score((c))) improved from low to medium (P<.001) among intervention
      patients and did not improve among controls. CONCLUSIONS: This study provides
      evidence that a focused diabetes care delivery intervention can be initiated in
      the ED among adults with type 2 diabetes and hyperglycemia and safely and
      effectively completed in the ambulatory setting. Improvement in short-term
      glycemic outcomes and medication adherence were observed.

PMID- 26214112
TI  - TRANSGENDER CARE: TRANSITIONING THE TRAINEE.

PMID- 26214113
TI  - GERMLINE DELETION OF ARMC5 IN FAMILIAL PRIMARY MACRONODULAR ADRENAL HYPERPLASIA.
AB  - OBJECTIVE: Primary macronodular adrenal hyperplasia (PMAH) is considered a
      predominantly sporadic disease, but familial forms are well recognized. Genetic
      studies revealed germline mutations in the armadillo repeat containing 5 gene
      (ARMC5) in the majority of PMAH cases. Furthermore, somatic ARMC5 mutations, as
      different types of second-hit mutations and loss of heterozygosity have been
      reported in each adrenal nodule in PMAH. Here, we describe the involvement of
      ARMC5 alteration in a familial case of PMAH. METHODS: In our study, we performed
      clinical and genetic evaluations in a mother and her son with familial PMAH. To
      search for mutations and deletion of ARMC5, we used Sanger sequencing and droplet
      digital polymerase chain reaction (ddPCR), respectively. RESULTS: Both patients
      showed the same phenotype of subclinical Cushing syndrome, with mild excess of
      mineralocorticoids and vasopressin-responsive cortisol secretion. The ddPCR
      analysis demonstrated that both mother and son had germline deletions in exons 1
      to 5 of the ARMC5 gene locus. Furthermore, Sanger sequencing of DNA from the
      right and left adrenal nodules as well as peripheral blood of the son revealed
      the presence of another germline, missense mutation in ARMC5 exon 3 (p.P347S).
      CONCLUSION: This is the first report demonstrating germline deletion of ARMC5 in
      familial PMAH. In addition to investigating mutations, germline and somatic
      deletions of ARMC5 could be examined by ddPCR, which permits rapid and accurate
      evaluation of the ARMC5 allelic status.

PMID- 26214114
TI  - THE VALUE OF GROSS VISUAL ASSESSMENT OF SPECIMEN ADEQUACY FOR LIQUID-BASED
      CYTOLOGY DURING ULTRASOUND-GUIDED, FINE-NEEDLE ASPIRATION OF THYROID NODULES.
AB  - OBJECTIVE: Major problems of fine-needle aspiration (FNA) of thyroid nodules
      arise due to nondiagnostic results caused by inadequately obtained FNA specimens.
      The purpose of this study was to evaluate the value of visual assessment of
      liquid-based cytology specimens during FNA of thyroid nodules for predicting
      sampling adequacy. METHODS: For 3 months, visual assessment of FNA specimens was
      used for 534 consecutive nodules in 534 patients. The FNA specimens were visually
      graded immediately following aspiration for each nodule, and the visual grades
      were classified into 2 categories: inadequate (<6 cell groups) and adequate (>6
      cell groups). The cytology results were classified as diagnostic or nondiagnostic
      based on the Bethesda system. We compared the ultrasound features and FNA
      characteristics between the diagnostic and nondiagnostic results. Multiple
      logistic regression analysis was used to determine factors independently
      predictive of nondiagnostic results. We also evaluated the interobserver
      agreement regarding the visual assessment. RESULTS: Visual assessment was
      feasible in all patients, and the nondiagnostic rate was 11.6% (62 of 534).
      Nondiagnostic results were more frequent in the inadequate visual assessment
      group (38.1%) than in the adequate visual assessment group (10.5%) (P = .001).
      Independent predictive factors for nondiagnostic results were inadequate visual
      assessment (odds ratio, 5.18), >50% vascularity (odds ratio, 3.98), and
      macrocalcification (odds ratio, 3.60). Interobserver agreement for the prediction
      of visual assessment was good (kappa value, 0.767; P<.001). CONCLUSION: Immediate
      visual assessment of a specimen during FNA of a thyroid nodule is a feasible
      method for predicting sampling adequacy.

PMID- 26214115
TI  - Stereoselective Synthesis of 3-Carboxy-4,5-dihydropyrroles via an Intramolecular
      Iminium Ion Cyclization Reaction.
AB  - An efficient and practical method has been developed for the synthesis of trans
      4,5-disubstituted 3-carboxy-4,5-dihydropyrroles via an intramolecular iminium ion
      cyclization reaction of readily accessible Baylis-Hillman derivatives and
      aldehydes in moderate to high yield. These new dihydropyrroles could be easily
      converted to pyrroles or pyrrolidines. 

PMID- 26214117
TI  - CYP24A1 Mutations in a Cohort of Hypercalcemic Patients: Evidence for a Recessive
      Trait.
AB  - CONTEXT: Loss-of-function mutations of CYP24A1 (which encodes the 25-OH-D3-24
      hydroxylase) have recently been reported to cause hypercalcemia. OBJECTIVES: The
      aims of this study were: 1) to evaluate the frequency of CYP24A1 mutations in
      patients with medical history of hypercalcemia; 2) to show the clinical utility
      of a simultaneous assay of serum 25-hydroxyvitamin D3 (25-OH-D3) and 24,25
      dihydroxyvitamin D3 (24,25-[OH]2D3) by liquid chromatography tandem mass
      spectrometry (LC-MS/MS); and 3) to investigate biochemical parameters in
      heterozygous gene carriers with CYP24A1 mutations. PATIENTS AND METHODS: We
      screened for CYP24A1 mutations in 72 patients with serum calcium levels > 2.6
      mmol/L and PTH levels < 20 pg/mL and recruited 24 relatives after genetic
      counseling for subsequent investigations. Vitamin D metabolite concentrations
      were assessed in a subset of patients by LC-MS/MS and results expressed as a
      ratio (R) of 25-OH-D3:24,25-(OH)2D3. RESULTS: Twenty-five patients with
      hypercalcemia (35%) harbored CYP24A1 variations. Twenty (28%) had biallelic
      variations, mostly found in subjects with nephrocalcinosis or renal stones
      (19/20). Five patients, all neonates, were heterozygous, without renal disease.
      We describe 15 new variations leading to loss-of-function according to
      pathogenicity prediction programs, and we functionally characterized 5 of them in
      vitro. A dramatic increase of R, usually >80, was found in patients harboring
      biallelic mutations providing evidence in vivo for the loss of CYP24A1 activity.
      In contrast, R value remains <25 in patients without CYP24A1 mutations. Subjects
      carrying one mutant allele, hypercalcemic individuals, as well as gene-carrier
      relatives, had a detectable 24,25-(OH)2D3 level and R < 25, indicating normal 24
      hydroxylase activity. CONCLUSION: CYP24A1 biallelic mutations are frequently
      found in patients presenting with hypercalcemia, low PTH, and renal disease. We
      confirm the accuracy and effectiveness of a novel blood test estimating the ratio
      between relevant vitamin D metabolites as a useful screening tool for CYP24A1
      mutations. Haploinsufficiency is not associated with CYP24A1 deficiency.

PMID- 26214116
TI  - Repetitive Mild Traumatic Brain Injury in the Developing Brain: Effects on Long
      Term Functional Outcome and Neuropathology.
AB  - Although accumulating evidence suggests that repetitive mild TBI (rmTBI) may
      cause long-term cognitive dysfunction in adults, whether rmTBI causes similar
      deficits in the immature brain is unknown. Here we used an experimental model of
      rmTBI in the immature brain to answer this question. Post-natal day (PND) 18 rats
      were subjected to either one, two, or three mild TBIs (mTBI) or an equivalent
      number of sham insults 24 h apart. After one or two mTBIs or sham insults,
      histology was evaluated at 7 days. After three mTBIs or sham insults, motor (d1
      5), cognitive (d11-92), and histological (d21-92) outcome was evaluated. At 7
      days, silver degeneration staining revealed axonal argyrophilia in the external
      capsule and corpus callosum after a single mTBI, with a second impact increasing
      axonal injury. Iba-1 immunohistochemistry showed amoeboid shaped microglia within
      the amygdalae bilaterally after mTBI. After three mTBI, there were no differences
      in beam balance, Morris water maze, and elevated plus maze performance versus
      sham. The rmTBI rats, however, showed impairment in novel object recognition and
      fear conditioning. Axonal silver staining was observed only in the external
      capsule on d21. Iba-1 staining did not reveal activated microglia on d21 or d92.
      In conclusion, mTBI results in traumatic axonal injury and microglial activation
      in the immature brain with repeated impact exacerbating axonal injury. The rmTBI
      in the immature brain leads to long-term associative learning deficit in
      adulthood. Defining the mechanisms damage from rmTBI in the developing brain
      could be vital for identification of therapies for children.

PMID- 26214118
TI  - Timing of Environmental Exposures as a Critical Element in Breast Cancer Risk.
AB  - OBJECTIVE: The role of the chemical environment in disease initiation or
      progression is becoming more evident. Endocrine disruption via environmental
      chemicals is now well documented in humans, rodent research models, and wildlife.
      Breast cancer is an endocrine-based disease whose risk may be modified by
      environmental exposures. Our purpose is to encourage more investigation into
      early life environmental exposures as they relate to breast cancer risk factors
      and disease over a lifetime. EVIDENCE: The 2009 President's Cancer Panel, 2012
      Institute of Medicine, 2013 Interagency Breast Cancer and the Environment
      Research Coordinating Committee reports, and research publications dated >=2012
      in PubMed were used to inform our perspective. CONSENSUS PROCESS: Literature was
      reviewed and evidence gathered on the effects of the environment on risk of
      breast cancer or mammary tumor development in animal research models as it
      pertained to the influence of timing of exposure on later-life outcomes.
      CONCLUSIONS: Evidence has accumulated for several chemicals that environmental
      factors have a stronger effect on breast cancer risk when exposure occurred early
      in life. The insecticide, dichlorodiphenyltrichloroethane, is an excellent
      example and is just one of several chemicals for which there seems to be both
      animal and human evidence for the developmental basis of adult disease. The
      developing breast undergoes many changes in early life, leaving it vulnerable to
      the effects of epigenetic marks, endocrine disruption, and carcinogens. More
      research is needed in the area of early beginnings of breast cancer, with
      prevention of the disease as the ultimate goal.

PMID- 26214119
TI  - Pulmonary Phototherapy for Treating Carbon Monoxide Poisoning.
AB  - RATIONALE: Carbon monoxide (CO) exposure is a leading cause of poison-related
      mortality. CO binds to Hb, forming carboxyhemoglobin (COHb), and produces tissue
      damage. Treatment of CO poisoning requires rapid removal of CO and restoration of
      oxygen delivery. Visible light is known to effectively dissociate CO from Hb,
      with a single photon dissociating one CO molecule. OBJECTIVES: To determine
      whether illumination of the lungs of CO-poisoned mice causes dissociation of COHb
      from blood transiting the lungs, releasing CO into alveoli and thereby enhancing
      the rate of CO elimination. METHODS: We developed a model of CO poisoning in
      anesthetized and mechanically ventilated mice to assess the effects of direct
      lung illumination (phototherapy) on the CO elimination rate. Light at wavelengths
      between 532 and 690 nm was tested. The effect of lung phototherapy administered
      during CO poisoning was also studied. To avoid a thoracotomy, we assessed the
      effect of lung phototherapy delivered to murine lungs via an optical fiber placed
      in the esophagus. MEASUREMENTS AND MAIN RESULTS: In CO-poisoned mice,
      phototherapy of exposed lungs at 532, 570, 592, and 628 nm dissociated CO from Hb
      and doubled the CO elimination rate. Phototherapy administered during severe CO
      poisoning limited the blood COHb increase and improved the survival rate.
      Noninvasive transesophageal phototherapy delivered to murine lungs via an optical
      fiber increased the rate of CO elimination while avoiding a thoracotomy.
      CONCLUSIONS: Future development and scaling up of lung phototherapy for patients
      with CO exposure may provide a significant advance for treating and preventing CO
      poisoning.

PMID- 26214120
TI  - Scanning Electron Microscope Characterization of Erosive Enamel in Human Teeth.
AB  - This study aimed to examine the surface characteristics of erosive enamel in
      extracted human teeth by scanning electron microscopy. Morphologic changes in
      naturally eroded enamel depend on the stages of dental erosion. In its early
      stages, the enamel surfaces show a honeycomb appearance due to the dissolution of
      enamel rod ends. In its advanced stages, the erosive process involves the
      underlying dentin and the eroded dentin shows exposed dentinal tubules and the
      dentinal matrix may be exposed due to the dissolution of the peri- and
      intertubular dentin. Evidence of remineralization is seen at the early stage of
      natural dental erosion. 

PMID- 26214121
TI  - Clinical efficacy and safety of ruxolitinib in the management of myelofibrosis: A
      single institution experience in Taiwan.
AB  - OBJECTIVE: Myelofibrosis (MF) is a pathologic entity of myeloproliferative
      neoplasm (MPN) characterized by bone marrow fibrosis, extramedullary
      hematopoiesis, splenomegaly, and constitutional symptoms that severely affect the
      quality of life accompanied with the risk of leukemia development. Conventional
      treatment is usually ineffective and has limited impact on prolongation of
      survival. Dysregulated Janus kinase (JAK) signaling is common in MPN. In two
      randomized controlled trials, ruxolitinib, a potent pan-JAK inhibitor, has been
      shown to be highly effective in patients with intermediate- and high-risk MF.
      METHOD: We retrospectively analyzed the therapeutic outcome of 10 MF patients
      treated with ruxolitinib in our institute. Basic clinical data, JAK2V617F
      mutational status and Myelofibrosis Symptoms Assessment Form (MF-SAF) to evaluate
      disease-related symptoms were recorded initially, and at every visit. RESULT:
      Among these patients, only half of the patients harbored JAK2V617F mutation.
      After treatment with ruxolitinib, all patients had reduction of splenic size and
      reached nadir by week 24. Nine patients had body weight increment, and four of
      them had body weight increment more than 10%. Seven patients had their total
      symptom score reduced by more than 50% after therapy. The efficacy of ruxolitinib
      was irrelevant to JAK2V617F mutational status. Adverse events were mainly
      hematological and easily manageable. DISCUSSION AND CONCLUSION: Ruxolitinib is
      both safe and efficacious in a cohort of Asian patients with MF. The efficacy of
      ruxolitinib is irrelevant to the mutational status of JAK2V617F.

PMID- 26214122
TI  - Hybridization in Three Dimensions: A Novel Route toward Plasmonic Metamolecules.
AB  - Plasmonic metamolecules have received much interest in the last years because
      they can produce a wide spectrum of different hybrid optical resonances. Most of
      the configurations presented so far, however, considered planar resonators lying
      on a dielectric substrate. This typically yields high damping and radiative
      losses, which severely limit the performance of the system. Here we show that
      these limits can be overcome by considering a 3D arrangement made from slanted
      nanorod dimers extruding from a silver baseplate. This configuration mimics an
      out-of-plane split ring resonator capable of a strong near-field interaction at
      the terminations and a strong diffractive coupling with nearby nanostructures.
      Compared to the corresponding planar counterparts, higher values of electric and
      magnetic fields are found (about a factor 10 and a factor 3, respectively). High
      quality-factor resonances (Q ~ 390) are produced in the mid-IR as a result of the
      efficient excitation of collective modes in dimer arrays. 

PMID- 26214123
TI  - Environmental and Pathogenic Factors Inducing Brown Apical Necrosis on Fruit of
      English (Persian) Walnut.
AB  - Brown apical necrosis (BAN) is a most recently described disease affecting
      English (Persian) walnut fruit. BAN was only recorded in intensively managed
      walnut orchards and was found to be a disease complex mainly caused by Fusarium
      species. All fungi associated with this disease are polyphagous and ubiquitous,
      not specific to walnut. Consequently, BAN occurrence is more strictly dependent,
      than generally, on the interaction between pathological features and
      environmental conditions. Environmental variables identified with regression
      analysis showed that maximum temperature, angle of main wind direction versus
      tree row orientation, and orchard distance to the closest river/canal, all
      representative of climatic conditions occurring in the orchard, were related to
      fruit drop. The factor displaying the highest influence on severity of BAN fruit
      drop was maximum temperature and only subordinately factors are associated with
      relative humidity. BAN symptoms were reproduced with in planta artificial
      inoculation, and fruit drop of symptomatic fruit was significantly higher than
      that of the noninoculated trees for each type of inoculum (Fusarium semitectum,
      F. graminearum, and Alternaria spp.). F. semitectum and F. graminearum were more
      aggressive than Alternaria species, and the earliest artificial inoculations in
      mid-May resulted in the highest fruit drop. The extension of walnut fruit
      susceptibility and the conducive environmental factors to BAN are discussed. 

PMID- 26214124
TI  - In Vitro Transcripts of Wild-Type and Fluorescent Protein-Tagged Triticum mosaic
      virus (Family Potyviridae) are Biologically Active in Wheat.
AB  - Triticum mosaic virus (TriMV) (genus Poacevirus, family Potyviridae) is a
      recently described eriophyid mite-transmitted wheat virus. In vitro RNA
      transcripts generated from full-length cDNA clones of TriMV proved infectious on
      wheat. Wheat seedlings inoculated with in vitro transcripts elicited mosaic and
      mottling symptoms similar to the wild-type virus, and the progeny virus was
      efficiently transmitted by wheat curl mites, indicating that the cloned virus
      retained pathogenicity, movement, and wheat curl mite transmission
      characteristics. A series of TriMV-based expression vectors was constructed by
      engineering a green fluorescent protein (GFP) or red fluorescent protein (RFP)
      open reading frame with homologous NIa-Pro cleavage peptides between the P1 and
      HC-Pro cistrons. We found that GFP-tagged TriMV with seven or nine amino acid
      cleavage peptides efficiently processed GFP from HC-Pro. TriMV-GFP vectors were
      stable in wheat for more than 120 days and for six serial passages at 14-day
      intervals by mechanical inoculation and were transmitted by wheat curl mites
      similarly to the wild-type virus. Fluorescent protein-tagged TriMV was observed
      in wheat leaves, stems, and crowns. The availability of fluorescent protein
      tagged TriMV will facilitate the examination of virus movement and distribution
      in cereal hosts and the mechanisms of cross protection and synergistic
      interactions between TriMV and Wheat streak mosaic virus. 

PMID- 26214125
TI  - Kadcoccinic Acids A-J, Triterpene Acids from Kadsura coccinea.
AB  - Eleven triterpene acids including 10 new compounds (kadcoccinic acids A-J, 1-10)
      were isolated from the stems of Kadsura coccinea. Except for 10, these compounds
      feature a rearranged lanostane skeleton with a 6/6/5/6 tetracyclic ring system,
      and compounds 1 and 2 are the first examples of 2,3-seco-6/6/5/6-fused
      tetracyclic triterpenoids. Their structures were established primarily by
      spectroscopic and spectrometric methods. Additionally, the absolute configuration
      of 3 was determined by single-crystal X-ray diffraction. Several of the compounds
      isolated were tested for their anti-HIV-1 and cytotoxic activities. 

PMID- 26214126
TI  - Fine-Tuning the Surface of Forward Osmosis Membranes via Grafting Graphene Oxide:
      Performance Patterns and Biofouling Propensity.
AB  - Graphene oxide (GO) nanosheets were attached to the polyamide selective layer of
      thin film composite (TFC) forward osmosis (FO) membranes through a poly L-Lysine
      (PLL) intermediary using either layer-by-layer or hybrid (H) grafting strategies.
      Fourier transform infrared spectroscopy, zeta potential, and thermogravimetric
      analysis confirmed the successful attachment of GO/PLL, the surface modification
      enhancing both the hydrophilicity and smoothness of the membrane's surface
      demonstrated by water contact angle, atomic force microscopy, and transmission
      electron microscopy. The biofouling resistance of the FO membranes determined
      using an adenosine triphosphate bioluminescence test showed a 99% reduction in
      surviving bacteria for GO/PLL-H modified membranes compared to pristine membrane.
      This antibiofouling property of the GO/PLL-H modified membrane was reflected in
      reduced flux decline compared to all other samples when filtering brackish water
      under biofouling conditions. Further, the high density and tightly bound GO
      nanosheets using the hybrid modification reduced the reverse solute flux compared
      to the pristine, which reflects improved membrane selectivity. These results
      illustrate that the GO/PLL-H modification is a valuable addition to improve the
      performance of FO TFC membranes.

PMID- 26214127
TI  - Chemical composition and antibacterial activity of the essential oil from
      Pyrrosia tonkinensis (Giesenhagen) Ching.
AB  - The present study aimed to analyse the chemical components of the essential oil
      from Pyrrosia tonkinensis by GC-MS and evaluate the in vitro antibacterial
      activity. Twenty-eight compounds, representing 88.1% of the total essential oil,
      were identified and the major volatile components were trans-2-hexenal (22.1%),
      followed by nonanal (12.8%), limonene (9.6%), phytol (8.4%), 1-hexanol (3.8%), 2
      furancarboxaldehyde (3.5%) and heptanal (3.1%). The antibacterial assays showed
      that the essential oil of P. tonkinensis had good antibacterial activities
      against all the tested microorganisms. This paper first reported the chemical
      composition and antimicrobial activity of the essential oil from P. tonkinensis. 

PMID- 26214128
TI  - A microfluidic device for epigenomic profiling using 100 cells.
AB  - The sensitivity of chromatin immunoprecipitation (ChIP) assays poses a major
      obstacle for epigenomic studies of low-abundance cells. Here we present a
      microfluidics-based ChIP-seq protocol using as few as 100 cells via drastically
      improved collection of high-quality ChIP-enriched DNA. Using this technology, we
      uncovered many new enhancers and super enhancers in hematopoietic stem and
      progenitor cells from mouse fetal liver, suggesting that enhancer activity is
      highly dynamic during early hematopoiesis. 

PMID- 26214129
TI  - Ultrafast, temporally stochastic STED nanoscopy of millisecond dynamics.
AB  - Electro-optical scanning (>1,000 frames/s) with pixel dwell times on the order of
      the lifetime of the fluorescent molecular state renders stimulated emission
      depletion (STED) nanoscopy temporally stochastic. Photon detection from a
      molecule occurs stochastically in one of several scanning frames, and the spatial
      origin of the photon is known with subdiffraction precision. Images are built up
      by binning consecutive frames, making the time resolution freely adjustable. We
      demonstrated nanoscopy of vesicle motions in living Drosophila larvae and the
      cellular uptake of viral particles with 5- to 10-ms temporal resolution. 

PMID- 26214130
TI  - Efficient and quantitative high-throughput tRNA sequencing.
AB  - Despite its biological importance, tRNA has not been adequately sequenced by
      standard methods because of its abundant post-transcriptional modifications and
      stable structure, which interfere with cDNA synthesis. We achieved efficient and
      quantitative tRNA sequencing in HEK293T cells by using engineered demethylases to
      remove base methylations and a highly processive thermostable group II intron
      reverse transcriptase to overcome these obstacles. Our method, DM-tRNA-seq,
      should be applicable to investigations of tRNA in all organisms. 

PMID- 26214131
TI  - Placental laterality and uterine blood flow at 20-40 weeks' gestation in low-risk
      pregnancies.
AB  - We sought to examine flow velocity waveforms of the uterine arteries with respect
      to placental location at 20-40 weeks' gestation. Blood flow (BF) volume,
      pulsatility index (PI), resistance index (RI), end-diastolic velocity, mean
      velocity, peak systolic velocity and systolic/diastolic ratio (S/D) were obtained
      by colour Doppler ultrasonography from bilateral uterine arteries in 288 low-risk
      singleton pregnancies. In cases with lateral placentation the mean PI and RI
      values at 36-40 weeks' gestation and the mean S/D value at 38-40 weeks were
      significantly higher in the contralateral than in the ipsilateral uterine
      arteries. Both BF volume and RI correlated inversely with gestational age in
      these groups (r = - 0.20 and p = 0.01; r = - 0.17 and p = 0.03, respectively).
      The contralateral and central uterine arteries were comparable for all Doppler
      indices. In conclusion, lateral placentation may affect uterine artery blood flow
      throughout gestation and some Doppler indices near term. Clinical significance of
      these findings needs to be elucidated. 

PMID- 26214132
TI  - Generation of vascular endothelial and smooth muscle cells from human pluripotent
      stem cells.
AB  - The use of human pluripotent stem cells for in vitro disease modelling and
      clinical applications requires protocols that convert these cells into relevant
      adult cell types. Here, we report the rapid and efficient differentiation of
      human pluripotent stem cells into vascular endothelial and smooth muscle cells.
      We found that GSK3 inhibition and BMP4 treatment rapidly committed pluripotent
      cells to a mesodermal fate and subsequent exposure to VEGF-A or PDGF-BB resulted
      in the differentiation of either endothelial or vascular smooth muscle cells,
      respectively. Both protocols produced mature cells with efficiencies exceeding
      80% within six days. On purification to 99% via surface markers, endothelial
      cells maintained their identity, as assessed by marker gene expression, and
      showed relevant in vitro and in vivo functionality. Global transcriptional and
      metabolomic analyses confirmed that the cells closely resembled their in vivo
      counterparts. Our results suggest that these cells could be used to faithfully
      model human disease. 

PMID- 26214135
TI  - Correction to Fragment-Based Discovery of Indole Inhibitors of Matrix
      Metalloproteinase-13.

PMID- 26214133
TI  - Intestinal inhibition of Atg7 prevents tumour initiation through a microbiome
      influenced immune response and suppresses tumour growth.
AB  - Here, we show that autophagy is activated in the intestinal epithelium in murine
      and human colorectal cancer and that the conditional inactivation of Atg7 in
      intestinal epithelial cells inhibits the formation of pre-cancerous lesions in
      Apc(+/-) mice by enhancing anti-tumour responses. The antibody-mediated depletion
      of CD8(+) T cells showed that these cells are essential for the anti-tumoral
      responses mediated by the inhibition of autophagy. We show that Atg7 deficiency
      leads to intestinal dysbiosis and that the microbiota is required for anticancer
      responses. In addition, Atg7 deficiency resulted in a stress response accompanied
      by metabolic defects, AMPK activation and p53-mediated cell-cycle arrest in
      tumour cells but not in normal tissue. This study reveals that the inhibition of
      autophagy within the epithelium may prevent the development and progression of
      colorectal cancer in genetically predisposed patients. 

PMID- 26214134
TI  - NF-kappaB activation impairs somatic cell reprogramming in ageing.
AB  - Ageing constitutes a critical impediment to somatic cell reprogramming. We have
      explored the regulatory mechanisms that constitute age-associated barriers,
      through derivation of induced pluripotent stem cells (iPSCs) from individuals
      with premature or physiological ageing. We demonstrate that NF-kappaB activation
      blocks the generation of iPSCs in ageing. We also show that NF-kappaB repression
      occurs during cell reprogramming towards a pluripotent state. Conversely, ageing
      associated NF-kappaB hyperactivation impairs the generation of iPSCs by eliciting
      the reprogramming repressor DOT1L, which reinforces senescence signals and
      downregulates pluripotency genes. Genetic and pharmacological NF-kappaB
      inhibitory strategies significantly increase the reprogramming efficiency of
      fibroblasts from Nestor-Guillermo progeria syndrome and Hutchinson-Gilford
      progeria syndrome patients, as well as from normal aged donors. Finally, we
      demonstrate that DOT1L inhibition in vivo extends lifespan and ameliorates the
      accelerated ageing phenotype of progeroid mice, supporting the interest of
      studying age-associated molecular impairments to identify targets of rejuvenation
      strategies. 

PMID- 26214136
TI  - Numerical investigations of rib fracture failure models in different dynamic
      loading conditions.
AB  - Rib fracture is one of the most common thoracic injuries in vehicle traffic
      accidents that can result in fatalities associated with seriously injured
      internal organs. A failure model is critical when modelling rib fracture to
      predict such injuries. Different rib failure models have been proposed in
      prediction of thorax injuries. However, the biofidelity of the fracture failure
      models when varying the loading conditions and the effects of a rib fracture
      failure model on prediction of thoracic injuries have been studied only to a
      limited extent. Therefore, this study aimed to investigate the effects of three
      rib failure models on prediction of thoracic injuries using a previously
      validated finite element model of the human thorax. The performance and
      biofidelity of each rib failure model were first evaluated by modelling rib
      responses to different loading conditions in two experimental configurations: (1)
      the three-point bending on the specimen taken from rib and (2) the anterior
      posterior dynamic loading to an entire bony part of the rib. Furthermore, the
      simulation of the rib failure behaviour in the frontal impact to an entire thorax
      was conducted at varying velocities and the effects of the failure models were
      analysed with respect to the severity of rib cage damages. Simulation results
      demonstrated that the responses of the thorax model are similar to the general
      trends of the rib fracture responses reported in the experimental literature.
      However, they also indicated that the accuracy of the rib fracture prediction
      using a given failure model varies for different loading conditions. 

PMID- 26214137
TI  - Identification and characterization of cytosolic fructose-1,6-bisphosphatase in
      Euglena gracilis.
AB  - Euglena gracilis has the ability to accumulate a storage polysaccharide, a beta
      1,3-glucan known as paramylon, under aerobic conditions. Under anaerobic
      conditions, E. gracilis cells degrade paramylon and synthesize wax esters.
      Cytosolic fructose-1,6-bisphosphatase (FBPase) appears to be a key enzyme in
      gluconeogenesis and position branch point of carbon partitioning between
      paramylon and wax ester biosynthesis. We herein identified and characterized
      cytosolic FBPase from E. gracilis. The Km and Vmax values of EgFBPaseIII were
      16.5 +/- 1.6 MUM and 30.4 +/- 7.2 MUmol min(-1) mg protein(-1), respectively. The
      activity of EgFBPaseIII was not regulated by AMP or reversible redox modulation.
      No significant differences were observed in the production of paramylon in
      transiently suppressed EgFBPaseIII gene expression cells by RNAi (KD
      EgFBPaseIII); nevertheless, FBPase activity was markedly decreased in KD
      EgFBPaseIII cells. On the other hand, the growth of KD-EgFBPaseIII cells was
      slightly higher than that of control cells.

PMID- 26214139
TI  - Autologous reconstitution leading to sustained JAK2-V617F negativity post
      allogeneic hematopoietic stem cell transplant in JAK2-V617F positive
      myelofibrosis.

PMID- 26214138
TI  - Predicting survival using clinical risk scores and non-HLA immunogenetics.
AB  - Previous studies of non-histocompatibility leukocyte antigen (HLA) gene single
      nucleotide polymorphisms (SNPs) on subgroups of patients undergoing allogeneic
      haematopoietic stem cell transplantation (HSCT) revealed an association with
      transplant outcome. This study further evaluated the association of non-HLA
      polymorphisms with overall survival in a cohort of 762 HSCT patients using data
      on 26 polymorphisms in 16 non-HLA genes. When viewed in addition to an already
      established clinical risk score (EBMT-score), three polymorphisms: rs8177374 in
      the gene for MyD88-adapter-like (MAL; P=0.026), rs9340799 in the oestrogen
      receptor gene (ESR; P=0.003) and rs1800795 in interleukin-6 (IL-6; P=0.007) were
      found to be associated with reduced overall survival, whereas the haplo-genotype
      (ACC/ACC) in IL-10 was protective (P=0.02). The addition of these non-HLA
      polymorphisms in a Cox regression model alongside the EBMT-score improved
      discrimination between risk groups and increased the level of prediction compared
      with the EBMT-score alone (gain in prediction capability for EBMT-genetic-score
      10.8%). Results also demonstrated how changes in clinical practice through time
      have altered the effects of non-HLA analysis. The study illustrates the
      significance of non-HLA genotyping prior to HSCT and the importance of further
      investigation into non-HLA gene polymorphisms in risk prediction. 

PMID- 26214140
TI  - High-resolution electrohydrodynamic jet printing of small-molecule organic light
      emitting diodes.
AB  - The development of alternative organic light-emitting diode (OLED) fabrication
      technologies for high-definition and low-cost displays is an important research
      topic as conventional fine metal mask-assisted vacuum evaporation has reached its
      limit to reduce pixel sizes and manufacturing costs. Here, we report an
      electrohydrodynamic jet (e-jet) printing method to fabricate small-molecule OLED
      pixels with high resolution (pixel width of 5 MUm), which significantly exceeds
      the resolutions of conventional inkjet or commercial OLED display pixels. In
      addition, we print small-molecule emitting materials which provide a significant
      advantage in terms of device efficiency and lifetime compared to those with
      polymers. 

PMID- 26214141
TI  - Structure-property relationship of donor-acceptor acridones - an optical,
      electrochemical and computational study.
AB  - The synthesis of two neutral acridone derivatives was carried out to design media
      sensitive chromophores by taking advantage of intramolecular charge transfer
      (ICT) features. The molecules comprised two different donor-acceptor-donor
      triads, with absorption maxima at 425 nm and 520 nm, for the ketone and
      dicyanomethylene derivatives, respectively. The ketone variant exhibited
      fluorescence at room temperature, whereas the dicyanomethylene derivative was
      only emissive in frozen hexane. The ketone emission was highly solvatochromic,
      with Stokes shifts that ranged from 5000 cm(-1) to 10 000 cm(-1).
      Electrochemically, both compounds displayed similar oxidation potentials at
      approximately 0.35 V versus ferrocene/ferrocenium, which was anticipated since
      both systems employ the same ethynylaniline donor portion of the molecule,
      whereas only the 9-dicyanomethylene derivative showed a reduction peak at -1.5 V
      vs. Fc/Fc(+). Additional spectroelectro-chemical experiments supported a
      delocalized cationic charge on the ethynylaniline fragments during oxidation and
      that during electrochemical reduction the dicyanomethylene moieties show
      localized anionic charge. All of the experimental observations are finally
      compared to DFT, TDDFT and NICS(0) computations to gain insight into the
      transitions involved and deduce the role of the acridone core in stabilizing its
      oxidized and reduced forms. 

PMID- 26214142
TI  - Adherence to a Yoga Program in Older Women with Knee Osteoarthritis.
AB  - Yoga is beneficial for osteoarthritis (OA) management in older adults; however,
      adherence to yoga practice is unknown. The purposes of this secondary analysis
      were to examine: (1) yoga adherence during the intervention and follow-up
      periods; (2) the relationship between social cognitive theory (SCT) constructs
      and adherence; and (3) the impact of adherence on OA-related symptoms in 36
      community-dwelling older women with knee OA. SCT was used as a framework to
      promote adherence to a yoga intervention program that included both
      group/homebased practices. Adherence to yoga was high during the intervention
      period but decreased over time. Although SCT was a useful framework for reducing
      attrition during the intervention, self-efficacy was the only construct that
      correlated with class attendance. Higher yoga adherence was correlated with
      improved symptoms, physical function, sleep quality, and quality of life. Yoga
      adherers were likely to be older, less educated, and had a lower body mass index
      than nonadherers. 

PMID- 26214143
TI  - Selenium supplementation for critically ill adults.
AB  - BACKGROUND: Selenium is a trace mineral essential to health and has an important
      role in immunity, defence against tissue damage and thyroid function. Improving
      selenium status could help protect against overwhelming tissue damage and
      infection in critically ill adults. This Cochrane review was originally published
      in 2004 updated in 2007 and again 2015. OBJECTIVES: The primary objective was to
      examine the effect of nutrition supplemented with selenium or ebselen on
      mortality in critically ill patients.The secondary objective was to examine the
      relationship between selenium or ebselen supplementation and number of
      infections, duration of mechanical ventilation, length of intensive care unit
      stay and length of hospital stay. SEARCH METHODS: In this update, we searched the
      current issue of the Cochrane Central Register of Controlled Trials, the Cochrane
      Library (2014, Issue 5); MEDLINE (Ovid SP, to May 20, 2014), EMBASE (Ovid SP, to
      May 20, 2014), CAB, BIOSIS and CINAHL. We handsearched the reference lists of the
      newest reviews and cross-checked with our search in MEDLINE. We contacted the
      main authors of included studies to request any missed, unreported or ongoing
      studies. The latest search was performed up to 21 May 2014. The search is now
      from inception until 21 May 2014. SELECTION CRITERIA: We included randomized
      controlled trials (RCTs) irrespective of publication status, date of publication,
      blinding status, outcomes published or language. We contacted the trial
      investigators and authors in order to retrieve relevant and missing data. DATA
      COLLECTION AND ANALYSIS: Two review authors independently extracted data and we
      resolved any disagreements by discussion. Our primary outcome measure was all
      cause mortality. We performed several subgroup and sensitivity analyses to assess
      the effects of selenium in critically ill patients. We presented pooled estimates
      of the effects of intervention as risk ratios (RRs) with 95% confidence intervals
      (CIs). We assessed the risk of bias through assessment of trial methodological
      components and the risk of random error through trial sequential analysis. MAIN
      RESULTS: We included six new RCTs in this review update. In total we included 16
      RCTs (2084 participants) in this review. Most trials were at high risk of bias.
      The availability of outcome data was limited and trials involving selenium
      supplementation were, with the exception of one trial, small regarding sample
      size. Thus the results must be interpreted with caution.Thirteen trials of
      intravenous sodium selenite showed a statistically significant reduction in
      overall mortality (RR 0.82, 95% CI 0.72 to 0.93, 1391 participants, very low
      quality of evidence). However, the overall point estimate on mortality is
      primarily influenced by trials of high risk of bias. Meta-analysis of three
      trials of ebselen had a RR of 0.83 (95% CI 0.52 to 1.34, 693 participants, very
      low quality of evidence).Nine trials of intravenous sodium selenite were analysed
      for 28 days mortality with no statistically significant difference (RR 0.84, 95%
      CI 0.69 to 1.02, 1180 participants, very low quality of evidence) while three
      trials were analysed for 90 days mortality with similar findings (RR 0.96, 95% Cl
      0.78 to 1.18, 614 participants, very low quality of evidence).Two trials of
      ebselen were analysed for 90 days mortality and were not found to yield any
      benefit (RR 0.72, 95% Cl 0.42 to 1.22, 588 participants, very low quality of
      evidence).For mortality among intensive care patients selenium supplementation
      failed to indicate any statistically significant advantage (RR 0.88, 95% CI 0.77
      to 1.01, nine trials, 1168 participants, very low quality of evidence).Six trials
      of intravenous sodium selenite found no statistically significant difference for
      participants developing infection (RR 0.96, 95% CI 0.75 to 1.23, 934 patients,
      very low quality of evidence). Similarly, three trials of ebselen provided data
      for participants developing infections (pyrexia, respiratory infections or
      meningitis) with no obvious benefit (RR 0.60, 95% CI 0.36 to 1.02, 685
      participants, very low quality of evidence).Our analyses showed no effect of
      selenium or ebselen on adverse events (Selenium: RR 1.03, 95% Cl 0.85 to 1.24;
      six trials, 925 participants ; Ebselen: RR 1.16, 95% CI 0.40 to 3.36; two trials,
      588 participants, very low quality of evidence).No clear evidence emerged in
      favour of selenium supplementation for outcomes such as number of days on a
      ventilator (mean difference (MD) -0.86, 95% CI -4.39 to 2.67, four trials, 191
      participants, very low quality of evidence), length of intensive care unit stay
      (MD 0.54, 95% CI -2.27 to 3.34, seven trials, 934 participants, very low quality
      of evidence) or length of hospital stay (MD -3.33, 95% Cl -5.22 to -1.44, five
      trials, 693 participants, very low quality of evidence).The quality of trial
      methodology was low. Due to high risk of bias in the included trials, results
      must be interpreted with caution. AUTHORS' CONCLUSIONS: Despite publication of a
      number of trials, the current evidence to recommend supplementation of critically
      ill patients with selenium or ebselen remains disputed. Trials are required which
      overcome the methodological inadequacies of the reviewed studies, particularly in
      relation to sample size, design and outcomes.

PMID- 26214144
TI  - Inverted methoxypyridinium phthalocyanines for PDI of pathogenic bacteria.
AB  - Phthalocyanines (Pc) are photoactive molecules that can absorb and emit light in
      a large range of the UV-Vis spectrum with recognized potential for medical
      applications. Considering the biomedical applications an important limitation of
      these compounds is their low solubility in water. The use of suitable pyridinium
      groups on Pc is a good strategy to solve this drawback and to make them more
      effective to photoinactivate Gram-negative bacteria via a photodynamic
      inactivation (PDI) approach. Herein, an easy synthetic access to obtain inverted
      tetra- and octa-methoxypyridinium phthalocyanines (compounds 5 and 6) and also
      their efficiency to photoinactivate a recombinant bioluminescent strain of
      Escherichia coli is described. The obtained results were compared with the ones
      obtained when more conventional thiopyridinium phthalocyanines (compounds 7 and
      8) were used. This innovative study comparing thiopyridinium and inverted
      methoxypyridinium moieties on cationic Pc is reported for the first time taking
      into account the efficiency of singlet oxygen ((1)O2) generation, water
      solubility and uptake properties.

PMID- 26214145
TI  - Effect of intrinsic and extrinsic factors on the simulated D-band length of type
      I collagen.
AB  - A signature feature of collagen is its axial periodicity visible in TEM as
      alternating dark and light bands. In mature, type I collagen, this repeating
      unit, D, is 67 nm long. This periodicity reflects an underlying packing of
      constituent triple-helix polypeptide monomers wherein the dark bands represent
      gaps between axially adjacent monomers. This organization is visible distinctly
      in the microfibrillar model of collagen obtained from fiber diffraction. However,
      to date, no atomistic simulations of this diffraction model under zero-stress
      conditions have reported a preservation of this structural feature. Such a
      demonstration is important as it provides the baseline to infer response
      functions of physiological stimuli. In contrast, simulations predict a
      considerable shrinkage of the D-band (11-19%). Here we evaluate systemically the
      effect of several factors on D-band shrinkage. Using force fields employed in
      previous studies we find that irrespective of the temperature/pressure coupling
      algorithms, assumed salt concentration or hydration level, and whether or not the
      monomers are cross-linked, the D-band shrinks considerably. This shrinkage is
      associated with the bending and widening of individual monomers, but employing a
      force field whose backbone dihedral energy landscape matches more closely with
      our computed CCSD(T) values produces a small D-band shrinkage of < 3%. Since this
      force field also performs better against other experimental data, it appears that
      the large shrinkage observed in earlier simulations is a force-field artifact.
      The residual shrinkage could be due to the absence of certain atomic-level
      details, such as glycosylation sites, for which we do not yet have suitable data.

PMID- 26214146
TI  - Rational design of octahedron and nanowire CeO2@MnO2 core-shell heterostructures
      with outstanding rate capability for asymmetric supercapacitors.
AB  - Two kinds of novel CeO2@MnO2 nanostructures have been synthesized via a self
      assembly strategy. The as-prepared CeO2 nanowire@MnO2 nanostructures exhibited
      unprecedented pseudocapacitance performance (255 F g(-1)) with outstanding rate
      capability. A new mechanism based on the synergistic effect between CeO2 and MnO2
      was proposed to interpret this phenomenon. When assembled as an asymmetric
      supercapacitor, an energy density of 27.5 W h kg(-1) with a maximum power density
      of 1.6 kW kg(-1) was achieved for CeO2 nanowire@MnO2 nanostructures. 

PMID- 26214147
TI  - Self-assembled NIR nanovesicles for long-term photoacoustic imaging in vivo.
AB  - We report a supramolecular approach for the preparation of photostable NIR
      nanovesicles based on a cyanine dye derivative as a photoacoustic (PA) contrast
      agent for high-performance nano-imaging. 

PMID- 26214148
TI  - Job Accommodations Availability and Utilization Among People With Lupus: An
      Examination of Workplace Activity Limitations and Work Context Factors.
AB  - OBJECTIVE: The aim of this study was to examine the availability of diverse job
      accommodations (or flexible working arrangements) and to describe their use among
      people with systemic lupus erythematosus (lupus), as well as to examine factors
      associated with the use of job accommodations. METHODS: A mail survey was sent to
      adult lupus patients receiving care from a lupus clinic based in Toronto, Canada.
      The survey assessed demographic information, self-reported disease activity, work
      history, workplace activity limitations, job strain, and the availability and use
      of job accommodations. Standard multivariable linear regression analysis was used
      to examine factors associated with the use of job accommodations. RESULTS: We
      received 362 responses of 604 mailed surveys (60% response rate). Participants
      who were employed within the last 5 years, but who were not currently working,
      were less likely than currently employed participants to report having had job
      accommodations available to them at their last place of employment. The use of
      job accommodations was reported by 70% of currently employed respondents and by
      72% of those not currently employed. The most common job accommodation used was
      sick leave days. Factors positively associated with the use of job accommodations
      among those who were employed included higher levels of education, being
      diagnosed with fibromyalgia, at least 1 episode of short-term work disability,
      not belonging to a union, greater workplace activity limitations, and greater job
      strain. CONCLUSION: The use of job accommodations among people with lupus is
      common. Work context factors, such as workplace activity limitations and job
      strain, are the main factors associated with the use of job accommodations.

PMID- 26214149
TI  - The Psychological Effects of Lung Cancer Screening on Heavy Smokers: Another
      Reason for Concern.

PMID- 26214151
TI  - RBC micromotors carrying multiple cargos towards potential theranostic
      applications.
AB  - Red blood cell (RBC)-based micromotors containing both therapeutic and diagnostic
      modalities are described as a means for potential theranostic applications. In
      this natural RBC-based multicargo-loaded micromotor system, quantum dots (QDs),
      anti-cancer drug doxorubicin (DOX), and magnetic nanoparticles (MNPs), were co
      encapsulated into RBC micromotors. The fluorescent emission of both QDs and DOX
      provides direct visualization of their loading inside the RBC motors at two
      distinct wavelengths. The presence of MNPs within the RBCs allows for efficient
      magnetic guidance under ultrasound propulsion along with providing the potential
      for magnetic resonance imaging. The simultaneous encapsulation of the imaging
      nanoparticles and therapeutic payloads within the same RBC micromotor has a
      minimal effect upon its propulsion behavior. The ability of the RBC micromotors
      to transport imaging and therapeutic agents at high speed and spatial precision
      through a complex microchannel network is also demonstrated. Such ability to load
      and transport diagnostic imaging agents and therapeutic drugs within a single
      cell-based motor, in addition to a lower toxicity observed once the drug is
      encapsulated within the multicargo RBC motor, opens the door to the development
      of theranostic micromotors that may simultaneously treat and monitor diseases. 

PMID- 26214150
TI  - Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle
      Aged Adults at Risk for Alzheimer Disease.
AB  - IMPORTANCE: Converging evidence suggests that Alzheimer disease (AD) involves
      insulin signaling impairment. Patients with AD and individuals at risk for AD
      show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled
      positron emission tomography (FDG-PET). OBJECTIVES: To determine whether insulin
      resistance predicts AD-like global and regional glucose metabolism deficits in
      late middle-aged participants at risk for AD and to examine whether insulin
      resistance-predicted variation in regional glucose metabolism is associated with
      worse cognitive performance. DESIGN, SETTING, AND PARTICIPANTS: This population
      based, cross-sectional study included 150 cognitively normal, late middle-aged
      (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for
      Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD
      parental history. Participants underwent cognitive testing, fasting blood draw,
      and FDG-PET at baseline. We used the homeostatic model assessment of peripheral
      insulin resistance (HOMA-IR). Regression analysis tested the statistical effect
      of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to
      determine whether HOMA-IR predicted regional glucose metabolism. Finally,
      predicted variation in regional glucose metabolism was regressed against
      cognitive factors. Covariates included age, sex, body mass index, apolipoprotein
      E epsilon4 genotype, AD parental history status, and a reference region used to
      normalize regional uptake. MAIN OUTCOMES AND MEASURES: Regional glucose uptake
      determined using FDG-PET and neuropsychological factors. RESULTS: Higher HOMA-IR
      was associated with lower global glucose metabolism (beta = -0.29; P < .01) and
      lower regional glucose metabolism across large portions of the frontal, lateral
      parietal, lateral temporal, and medial temporal lobes (P < .05, familywise error
      corrected). The association was especially robust in the left medial temporal
      lobe (R2 = 0.178). Lower glucose metabolism in the left medial temporal lobe
      predicted by HOMA-IR was significantly related to worse performance on the
      immediate memory (beta = 0.317; t148 = 4.08; P < .001) and delayed memory (beta =
      0.305; t148 = 3.895; P < .001) factor scores. CONCLUSIONS AND RELEVANCE: Our
      results show that insulin resistance, a prevalent and increasingly common
      condition in developed countries, is associated with significantly lower regional
      cerebral glucose metabolism, which in turn may predict worse memory performance.
      Midlife may be a critical period for initiating treatments to lower peripheral
      insulin resistance to maintain neural metabolism and cognitive function.

PMID- 26214152
TI  - Myocardial T1 mapping at 3.0 tesla using an inversion recovery spoiled gradient
      echo readout and bloch equation simulation with slice profile correction
      (BLESSPC) T1 estimation algorithm.
AB  - BACKGROUND: To develop an accurate and precise myocardial T1 mapping technique
      using an inversion recovery spoiled gradient echo readout at 3.0 Tesla (T).
      THEORY AND METHODS: The modified Look-Locker inversion-recovery (MOLLI) sequence
      was modified to use fast low angle shot (FLASH) readout, incorporating a BLESSPC
      (Bloch Equation Simulation with Slice Profile Correction) T1 estimation
      algorithm, for accurate myocardial T1 mapping. The FLASH-MOLLI with BLESSPC
      fitting was compared with different approaches and sequences with regards to T1
      estimation accuracy, precision and image artifact based on simulation, phantom
      studies, and in vivo studies of 10 healthy volunteers and three patients at 3.0
      Tesla. RESULTS: The FLASH-MOLLI with BLESSPC fitting yields accurate T1
      estimation (average error = -5.4 +/- 15.1 ms, percentage error = -0.5% +/- 1.2%)
      for T1 from 236-1852 ms and heart rate from 40-100 bpm in phantom studies. The
      FLASH-MOLLI sequence prevented off-resonance artifacts in all 10 healthy
      volunteers at 3.0T. In vivo, there was no significant difference between FLASH
      MOLLI-derived myocardial T1 values and "ShMOLLI+IE" derived values (1458.9 +/-
      20.9 ms versus 1464.1 +/- 6.8 ms, P = 0.50); However, the average precision by
      FLASH-MOLLI was significantly better than that generated by "ShMOLLI+IE" (1.84 +/
      0.36% variance versus 3.57 +/- 0.94%, P < 0.001). CONCLUSION: The FLASH-MOLLI
      with BLESSPC fitting yields accurate and precise T1 estimation, and eliminates
      banding artifacts associated with bSSFP at 3.0T.

PMID- 26214153
TI  - Vibrational mode assignment of finite temperature infrared spectra using the
      AMOEBA polarizable force field.
AB  - The calculation of infrared spectra by molecular dynamics simulations based on
      the AMOEBA polarizable force field has recently been demonstrated [Semrouni et
      al., J. Chem. Theory Comput., 2014, 10, 3190]. While this approach allows access
      to temperature and anharmonicity effects, band assignment requires additional
      tools, which we describe in this paper. The Driven Molecular Dynamics approach,
      originally developed by Bowman, Kaledin et al. [Bowman et al. J. Chem. Phys.,
      2003, 119, 646, Kaledin et al. J. Chem. Phys., 2004, 121, 5646] has been adapted
      and associated with AMOEBA. Its advantages and limitations are described. The IR
      spectrum of the Ac-Phe-Ala-NH2 model peptide is analyzed in detail. In addition
      to differentiation of conformations by reproducing frequency shifts due to non
      covalent interactions, DMD allows visualizing the temperature-dependent
      vibrational modes. 

PMID- 26214154
TI  - Waterproof Alkyl Phosphate Coated Fluoride Phosphors for Optoelectronic
      Materials.
AB  - A facile approach for coating red fluoride phosphors with a moisture-resistant
      alkyl phosphate layer with a thickness of 50-100 nm is reported. K2 SiF6 :Mn(4+)
      particles were prepared by co-precipitation and then coated by esterification of
      P2 O5 with alcohols (methanol, ethanol, and isopropanol). This route was adopted
      to encapsulate the prepared phosphors using transition-metal ions as cross
      linkers between the alkyl phosphate moieties. The coated phosphor particles
      exhibited a high water tolerance and retained approximately 87 % of their initial
      external quantum efficiency after aging under high-humidity (85 %) and high
      temperature (85  degrees C) conditions for one month. Warm white-light-emitting
      diodes that consisted of blue InGaN chips, the prepared K2 SiF6 :Mn(4+)
      phosphors, and either yellow Y3 Al5 O12 :Ce(3+) phosphors or green beta-SiAlON:
      Eu(2+) phosphors showed excellent color rendition. 

PMID- 26214155
TI  - Programmable chemical reaction networks: emulating regulatory functions in living
      cells using a bottom-up approach.
AB  - Living cells are able to produce a wide variety of biological responses when
      subjected to biochemical stimuli. It has become apparent that these biological
      responses are regulated by complex chemical reaction networks (CRNs). Unravelling
      the function of these circuits is a key topic of both systems biology and
      synthetic biology. Recent progress at the interface of chemistry and biology
      together with the realisation that current experimental tools are insufficient to
      quantitatively understand the molecular logic of pathways inside living cells has
      triggered renewed interest in the bottom-up development of CRNs. This builds upon
      earlier work of physical chemists who extensively studied inorganic CRNs and
      showed how a system of chemical reactions can give rise to complex spatiotemporal
      responses such as oscillations and pattern formation. Using purified biochemical
      components, in vitro synthetic biologists have started to engineer simplified
      model systems with the goal of mimicking biological responses of intracellular
      circuits. Emulation and reconstruction of system-level properties of
      intracellular networks using simplified circuits are able to reveal key design
      principles and molecular programs that underlie the biological function of
      interest. In this Tutorial Review, we present an accessible overview of this
      emerging field starting with key studies on inorganic CRNs followed by a
      discussion of recent work involving purified biochemical components. Finally, we
      review recent work showing the versatility of programmable biochemical reaction
      networks (BRNs) in analytical and diagnostic applications. 

PMID- 26214156
TI  - Thermal diffusivity measured using a single plasmonic nanoparticle.
AB  - A method to measure thermal diffusivity around a single heated gold nanoparticle
      is presented. It is based on photothermal single particle microscopy and employs
      the phase delay of temperature modulation due to finite thermal diffusivity. The
      phase delay is detected optically averaging over the focal volume of a
      diffraction limited beam of light. Thermal diffusivity is extracted by comparison
      to electromagnetic scattering calculations of the photothermal signal.
      Measurements in the solid (polymer) and liquid (water) are presented and compare
      well with literature data. The method paves the way for extended measurements of
      non-diffusive and heterogeneous heat transport in complex media. 

PMID- 26214157
TI  - What is your diagnosis? Swelling of the left antebrachium and carpus in a horse.

PMID- 26214158
TI  - Enhanced resistance in Theobroma cacao against oomycete and fungal pathogens by
      secretion of phosphatidylinositol-3-phosphate-binding proteins.
AB  - The internalization of some oomycete and fungal pathogen effectors into host
      plant cells has been reported to be blocked by proteins that bind to the
      effectors' cell entry receptor, phosphatidylinositol-3-phosphate (PI3P). This
      finding suggested a novel strategy for disease control by engineering plants to
      secrete PI3P-binding proteins. In this study, we tested this strategy using the
      chocolate tree Theobroma cacao. Transient expression and secretion of four
      different PI3P-binding proteins in detached leaves of T. cacao greatly reduced
      infection by two oomycete pathogens, Phytophthora tropicalis and Phytophthora
      palmivora, which cause black pod disease. Lesion size and pathogen growth were
      reduced by up to 85%. Resistance was not conferred by proteins lacking a
      secretory leader, by proteins with mutations in their PI3P-binding site, or by a
      secreted PI4P-binding protein. Stably transformed, transgenic T. cacao plants
      expressing two different PI3P-binding proteins showed substantially enhanced
      resistance to both P. tropicalis and P. palmivora, as well as to the fungal
      pathogen Colletotrichum theobromicola. These results demonstrate that secretion
      of PI3P-binding proteins is an effective way to increase disease resistance in T.
      cacao, and potentially in other plants, against a broad spectrum of pathogens.

PMID- 26214159
TI  - The association of antihypertensives with postural blood pressure and falls among
      seniors residing in the community: a case-control study.
AB  - BACKGROUND: A drop in postural blood pressure (BP) may contribute to falls, while
      antihypertensives have been considered to induce postural drop or orthostatic
      hypotension (OH) and falls among older people. However, this relationship between
      antihypertensives, postural BP and the risk of falls has never been evaluated in
      a single study. OBJECTIVE: To examine the association of postural BP changes and
      BP therapy with the risk of falls among community-dwelling older people in a case
      control manner. METHOD: Cases (n = 202) included participants aged >= 65 years
      with two falls or one injurious fall while controls (n = 156) included
      participants >= 65 years with no falls in the preceding 12 months.
      Antihypertensives usage and medical history were recorded. Supine BP measurements
      were obtained at 10 min rest and at 1, 2 and 3 min after standing. Orthostatic
      hypotension was defined as a reduction in BP of 20/10 mmHg within 3 min of
      standing. RESULTS: Individual antihypertensive classes were not associated with
      falls. Minimal standing systolic BP (SBP) was significantly lower among fallers
      [128 (+/- 27.3) vs. 135.7 (+/- 24.7) mmHg; P = 0.01], but fallers were not more
      likely to fulfil the diagnostic criteria for OH. Diuretics were associated with
      OH and alpha-blockers were associated with minimal standing SBP. Univariate
      analysis revealed that the use of >= 2 antihypertensives was associated with
      recurrent and injurious falls [OR,1.97;CI,1.2-3.1], which was no longer
      significant aftermultivariateadjustment for age and number of comorbidities [OR,
      1.6; CI, 0.95-2.6]. DISCUSSION: Minimal standing SBP or a lower SBP at 2 or
      3minutes standing was associated with falls rather than OH using consensus
      definition. Association between >= 2 antihypertensives and falls was attenuated
      by increasing age and comorbidities. Our findings challenge previous assumptions
      that OH or the use of antihypertensives is associated with falls. Future studies
      should now seek to link these findings prospectively with falls in order to guide
      decision-making for BP lowering therapy among older patients.

PMID- 26214160
TI  - Breast milk fatty acid composition has a long-term effect on the risk of asthma,
      eczema, and sensitization.
AB  - BACKGROUND: Levels of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs in
      breast milk are associated with the development of allergic diseases up to school
      age. However, it is unknown whether this relationship persists when the child
      becomes older. We therefore studied the association between levels of n-3 PUFAs
      and n-6 PUFAs in breast milk of allergic- and nonallergic mothers and asthma,
      eczema and sensitization up to the age of 14 years. METHODS: The study was nested
      in the ongoing PIAMA birth cohort. At the child's age of 3 months, 276 mothers
      provided a breast milk sample. Asthma (N total = 269) and eczema (N total = 274)
      were self-reported up to the child's age of 14 years. Specific serum IgE levels
      were measured at the ages of 4, 8 and 12 years (N total = 216). Generalized
      estimating equations analyses were used to take account of repeated observations.
      RESULTS: Asthma up to the age of 14 years is less prevalent in children of
      allergic mothers receiving breast milk with higher levels of n-3 long chain
      polyunsaturated (LCP) fatty acids (OR 0.50; 95% CI 0.31-0.79), and more prevalent
      in children of nonallergic mothers receiving breast milk with higher levels of n
      6LCP (OR 1.86; 95% CI 1.14-3.03). Weaker associations in similar direction were
      observed for eczema and sensitization. Direction of associations were consistent
      and of similar magnitude throughout childhood. CONCLUSION: The association
      between breast milk fatty acid composition and asthma, eczema and sensitization
      persists up to the age of 14 years in children of both allergic and nonallergic
      mothers.

PMID- 26214161
TI  - Circulating Endothelial Cells Expressing the Angiogenic Transcription Factor
      Kruppel-Like Factor 4 are Decreased in Patients with Coronary Artery Disease.
AB  - OBJECTIVE: The zinc finger transcription factor KLF4 is known to control diverse
      EC functions. METHODS: The functional role of KLF4 for angiogenesis and its
      association with CAD was examined in HUVECs and human CECs. RESULTS: In two
      different angiogenesis assays, siRNA-mediated KLF4 downregulation impaired HUVEC
      sprouting and network formation. Conversely, KLF4 overexpression increased HUVEC
      sprouting and network formation. Similar findings were observed after incubation
      of HUVECs with CdM from KLF4 cDNA-transfected cells, suggesting a role of
      paracrine factors for mediating angiogenic KLF4 effects. In this regard, VEGF
      expression was increased in KLF4-overexpressing HUVECs, whereas its expression
      was reduced in HUVECs transfected with KLF4 siRNA. To examine the relevance of
      our in vitro findings for human endothelial dysfunction, we analyzed the
      expression of KLF4 in CECs of patients with stable CAD. Flow cytometry analyses
      revealed decreased numbers of KLF4-positive CECs in peripheral blood from CAD
      patients compared to healthy controls. CONCLUSIONS: Our findings suggest that
      KLF4 may represent a potential biomarker for EC dysfunction. In the future,
      (therapeutic) modulation of KLF4 may be useful in regulating EC function during
      vascular disease processes.

PMID- 26214162
TI  - Covalently Coupled Ultrafine H-TiO2 Nanocrystals/Nitrogen-Doped Graphene Hybrid
      Materials for High-Performance Supercapacitor.
AB  - Hydrogenated TiO2 (H-TiO2) are considered one of the most promising materials for
      supercapacitors given its low-cost, high conductivity, and enhanced
      electrochemical activity. However, the electrochemical performances of H-TiO2 due
      to lacking suitable structures is unsatisfactory, and thus how to design
      energetic H-TiO2-based electrode architectures still remains a great challenge.
      Herein, covalently coupled ultrafine H-TiO2 nanocrystals/nitrogen-doped graphene
      (H-TiO2/NG) hybrid materials were developed through a simple hydrothermal route
      followed by hydrogenation. Within this architecture, the strong interaction
      between H-TiO2 nanocrystals and NG sheets via covalent chemical bonding affords
      high structural stability inhibiting the aggregation of H-TiO2 nanocrystals.
      Meanwhile, the NG matrices function as an electrical highway and a mechanical
      backbone so that most of well-dispersed ultrafine H-TiO2 nanocrystals are
      electrochemically active but stable. As a result, the optimized H-TiO2/NG (H
      TiO2/NG-B) exhibited high reversible specific capacity of 385.2 F g(-1) at 1 A g(
      1), enhanced rate performance of 320.1 F g(-1) at a high current density of 10 A
      g(-1), and excellent cycling stability with 98.8% capacity retention. 

PMID- 26214163
TI  - Perspective-taking in comprehension, production, and memory: An individual
      differences approach.
AB  - The ability to take a different perspective is central to a tremendous variety of
      higher level cognitive skills. To communicate effectively, we must adopt the
      perspective of another person both while speaking and listening. To ensure the
      successful retrieval of critical information in the future, we must adopt the
      perspective of our own future self and construct cues that will survive the
      passage of time. Here we explore the cognitive underpinnings of perspective
      taking across a set of tasks that involve communication and memory, with an eye
      toward evaluating the proposal that perspective-taking is domain-general (e.g.,
      Wardlow, 2013). We measured participants' perspective-taking ability in a
      language production task, a language comprehension task, and a memory task in
      which people generated their own cues for the future. Surprisingly, there was
      little variance common to the 3 tasks, a result that suggests that perspective
      taking is not domain-general. Performance in the language production task was
      predicted by a measure of working memory, whereas performance in the cue
      generation memory task was predicted by a combination of working memory and long
      term memory measures. These results indicate that perspective-taking relies on
      differing cognitive capacities in different situations.

PMID- 26214164
TI  - Hormones and ethics: Understanding the biological basis of unethical conduct.
AB  - Globally, fraud has been rising sharply over the last decade, with current
      estimates placing financial losses at greater than $3.7 trillion annually.
      Unfortunately, fraud prevention has been stymied by lack of a clear and
      comprehensive understanding of its underlying causes and mechanisms. In this
      paper, we focus on an important but neglected topic--the biological antecedents
      and consequences of unethical conduct--using salivary collection of hormones
      (testosterone and cortisol). We hypothesized that preperformance cortisol levels
      would interact with preperformance levels of testosterone to regulate cheating
      behavior in 2 studies. Further, based on the previously untested cheating-as
      stress-reduction hypothesis, we predicted a dose-response relationship between
      cheating and reductions in cortisol and negative affect. Taken together, this
      research marks the first foray into the possibility that endocrine-system
      activity plays an important role in the regulation of unethical behavior.

PMID- 26214165
TI  - Individual differences in the perception of melodic contours and pitch-accent
      timing in speech: Support for domain-generality of pitch processing.
AB  - Do the same mechanisms underlie processing of music and language? Recent
      investigations of this question have yielded inconsistent results. Likely factors
      contributing to discrepant findings are use of small samples and failure to
      control for individual differences in cognitive ability. We investigated the
      relationship between music and speech prosody processing, while controlling for
      cognitive ability. Participants (n = 179) completed a battery of cognitive
      ability tests, the Montreal Battery of Evaluation of Amusia (MBEA) to assess
      music perception, and a prosody test of pitch peak timing discrimination (early,
      as in insight vs. late, incite). Structural equation modeling revealed that only
      music perception was a significant predictor of prosody test performance. Music
      perception accounted for 34.5% of variance on prosody test performance; cognitive
      abilities and music training added only about 8%. These results indicate musical
      pitch and temporal processing are highly predictive of pitch discrimination in
      speech processing, even after controlling for other possible predictors of this
      aspect of language processing.

PMID- 26214166
TI  - Correction to Kreuzbauer, King, and Basu (2015).
AB  - Reports an error in "The Mind in the Object-Psychological Valuation of
      Materialized Human Expression" by Robert Kreuzbauer, Dan King and Shankha Basu
      (Journal of Experimental Psychology: General, Advanced Online Publication, Jun
      15, 2015, np). In the article the labels on the X-axis of Figure 1 "Remove
      Variance" and "Preserve Variance" should be switched. (The following abstract of
      the original article appeared in record 2015-26264-001.) Symbolic material
      objects such as art or certain artifacts (e.g., fine pottery, jewelry) share one
      common element: The combination of generating an expression, and the
      materialization of this expression in the object. This explains why people place
      a much greater value on handmade over machine-made objects, and originals over
      duplicates. We show that this mechanism occurs when a material object's symbolic
      property is salient and when the creator (artist or craftsman) is perceived to
      have agency control over the 1-to-1 materialized expression in the object.
      Coactivation of these 2 factors causes the object to be perceived as having high
      value because it is seen as the embodied representation of the creator's unique
      personal expression. In 6 experiments, subjects rated objects in various object
      categories, which varied on the type of object property (symbolic, functional,
      aesthetic), the production procedure (handmade, machine-made, analog, digital)
      and the origin of the symbolic information (person or software). The studies
      showed that the proposed mechanism applies to symbolic, but not to functional or
      aesthetic material objects. Furthermore, they show that this specific form of
      symbolic object valuation could not be explained by various other related
      psychological theories (e.g., uniqueness, scarcity, physical touching, creative
      performance). Our research provides a universal framework that identifies a core
      mechanism for explaining judgments of value for one of our most uniquely human
      symbolic object categories.

PMID- 26214167
TI  - Consequences of joint action: Entanglement with your partner.
AB  - Primates are expert tool users because they can adapt their body schemas to form
      a hand-tool joint representation that affords effective wielding. Here we extend
      the scope of this mechanism by proposing that humans are experts in social tasks
      because they can adjust their body schemas to incorporate the kinematics of
      partners, thus forming an interpersonal joint body schema. Participants engaged
      with a confederate in a 2-handed sawing task requiring each to use 1 hand. After
      active movement coordination, an interpersonal body schema was demonstrated in 2
      ways. First, there was interference between visual stimulation near 1 person's
      body and vibrotactile localization on the other person's body. Second, after
      active movement coordination, the motor output of 1 partner (attempting to draw
      straight lines) was affected by the viewed actions of the other partner (drawing
      ovals). This adaptation of the body schema may underlie the formation of cultural
      groups. In fact, participants with interdependent self-construals (typical of
      Asian cultures) form a stronger interpersonal joint body schema than do
      participants with independent self-construals (typical of North American and
      Western European cultures).

PMID- 26214168
TI  - Do subtle reminders of money change people's political views?
AB  - A number of researchers have reported studies showing that subtle reminders of
      money can alter behaviors and beliefs that are seemingly unrelated to money. In 1
      set of studies published in this journal, Caruso, Vohs, Baxter, and Waytz (2013)
      found that incidental exposures to money led subjects to indicate greater support
      for inequality, socioeconomic differences, group-based discrimination, and free
      market economies. We conducted high-powered replication attempts of these 4 money
      priming effects and found no evidence of priming (weighted Cohen's d = 0.03). We
      later learned that Caruso et al. also found several null effects in their line of
      research that were not reported in the original article. In addition, the money
      priming effect observed in the first study of Caruso et al. was included in the
      Many Labs Replication Project (Klein et al., 2014), and only 1 of the 36 labs was
      able to find the effect.

PMID- 26214169
TI  - Money priming can change people's thoughts, feelings, motivations, and behaviors:
      An update on 10 years of experiments.
AB  - Caruso, Vohs, Baxter, and Waytz (2013) posited that because money is used in free
      market exchanges, cues of money would lead people to justify and support the
      systems that allow those exchanges to take place. Hence, the authors predicted
      that money primes would boost system justification, social dominance, belief in a
      just world, and free market ideology, and found supportive evidence. Rohrer,
      Pashler, and Harris (2015) failed to replicate those effects. This article
      discusses the factors that predict priming effects, and particularly those
      pertinent to differences between Caruso et al. and Rohrer et al. Variations in a
      prime's meaning, the ease with which primed content comes to mind, the prime's
      motivational importance, and the ambiguity of the outcome situation influence the
      impact of the prime. Money priming experiments (totaling 165 to date, from 18
      countries) point to at least 2 major effects. First, compared to neutral primes,
      people reminded of money are less interpersonally attuned. They are not
      prosocial, caring, or warm. They eschew interdependence. Second, people reminded
      of money shift into professional, business, and work mentality. They exert effort
      on challenging tasks, demonstrate good performance, and feel efficacious. Money
      priming is not the same as priming another popular means of exchange, credit
      cards, and can have bigger effects when there is an implied connection between
      the self and having money. The practical benefits of money have been studied by
      other disciplines for decades, and the time is now for psychologists to study the
      effects of merely being reminded of money.

PMID- 26214170
TI  - Survival and prognostic factors in patients with connective tissue disease
      associated pulmonary hypertension diagnosed by echocardiography: results from a
      Korean nationwide registry.
AB  - OBJECTIVES: Pulmonary arterial hypertension (PAH) is a major cause of mortality
      in connective tissue disease (CTD). The survival rates and mortality-predictive
      factors of a nationwide registry of Korean patients with CTD-PH measured by
      echocardiography were determined. METHODS: Patients with CTD-PH were enrolled
      between April 2008 and December 2012. Hemodynamic parameters and clinical data
      (WHO-functional class [FC], organ involvement, laboratory tests and treatment
      agents) were recorded. Survival rates were calculated by using the Kaplan-Meier
      method. Mortality-associated factors were examined by Cox proportional hazards
      regression analysis. RESULTS: In total, 174 incident PH cases (61 with systemic
      lupus erythematosus, 50 with systemic sclerosis, 10 with mixed CTD, 22 with
      rheumatoid arthritis (RA) and 31 with other CTDs) were diagnosed by Doppler
      echocardiography. Of these, 25 (14%) died during the 3.8 +/- 2.7 year follow-up
      period after PH diagnosis. The 1- and 3-year survival rates were 90.7% and 87.3%,
      respectively. Compared to the other CTD-PHs, RA-PH had the lowest survival rates
      (56% 3 year survival; P = 0.022). Multiple regression analysis revealed that low
      diffusion capacity of carbon monoxide (DLCO), pleural effusion and diabetes
      mellitus were poor prognostic factors (P = 0.008, 0.04 and 0.009, respectively).
      Anti-UI-RNP (ribonucleoprotein) antibody positivity was protective (P = 0.022).
      In patients with WHO-FC III/IV, patients who received vasodilators had lower
      mortality than those who did not (P = 0.038). CONCLUSIONS: In Korean patients
      with CTD-PH, the 3-year survival rate was 87%. Low diffusion capacity of carbon
      monoxide (DLCO), pleural effusion and diabetes mellitus were independent poor
      prognostic factors. Anti-UI-RNP antibody was protective. Prompt PAH-specific
      vasodilator therapy may improve the survival of patients with severe CTD-PH.

PMID- 26214171
TI  - Azole-resistant Aspergillus fumigatus isolates carrying TR34/L98H mutations in
      Taiwan.
AB  - Cumulative evidence described the emergence and geographical expansion of azole
      resistant A. fumigatus associated with azole treatment failure. To investigate
      the status of azole resistance in A. fumigatus in Taiwan, we studied 38 A.
      fumigatus clinical isolates cultivated from 31 patients at two teaching hospitals
      from 2011 to 2014. Three isolates obtained from respiratory samples of two azole
      naive patients with pulmonary aspergillosis were found to display multi-azole
      resistance and cross resistance to agricultural azole fungicides, and all carried
      TR34/L98H mutations in cyp51A gene. The prevalence rates of azole resistance were
      7.9% and 6.5% based on isolates and patients respectively. A phylogenetic
      analysis suggested genetic diversity of the TR34/L98H isolates in Taiwan,
      including a unique genotype distinct from strains outside Taiwan. The result
      underlines the emergence of such isolates in Taiwan as well, emphasising the
      importance of further surveillance for azole-resistant A. fumigatus and
      implementation of strategies that prevent fungicide-driven resistance selection.

PMID- 26214172
TI  - UV Sensitivity of Vegetative and Reproductive Tissues of Two Antarctic Brown
      Algae is Related to Differential Allocation of Phenolic Substances.
AB  - UV sensitivity of the vegetative and reproductive tissues of two Antarctic brown
      macroalgae was compared. Photosynthesis as well as the content and localization
      of phenolic substances were determined. Responses to UV radiation were quantified
      as chlorophyll fluorescence (Fv /Fm ). Ascoseira mirabilis showed high UV
      tolerance, while in Cystosphaera jacquinotii Fv /Fm decreased by 15-21%, the
      receptacles being more tolerant than the vegetative blades. The phlorotannin
      contents showed an opposite pattern: the soluble fraction dominated in C.
      jacquinotii while in A. mirabilis the insoluble fraction was more abundant.
      Soluble phlorotannins were higher in the reproductive than in vegetative tissues
      in both species. Images of tissue cross-sections under violet-blue light
      excitation confirmed a high allocation of phenolic compounds (as blue
      autofluorescence) in C. jacquinotii, both in reproductive and vegetative blades.
      The allocation and proportions of the soluble and insoluble phlorotannins could
      be related with the observed UV tolerance of the vegetative and reproductive
      tissues. 

PMID- 26214173
TI  - A biofuel cell in non-aqueous solution.
AB  - We report the first example of a biofuel cell operating in organic solvents. The
      cell utilises glucose oxidase and bilirubin oxidase immobilised on nanoporous
      gold. The power output of the cell decreases with increasing solvent
      hydrophobicity in the alcohols, methanol (MeOH), ethanol (EtOH), 1-propanol
      (PrOH), 1-butanol (BuOH) and 1-pentanol (PeOH). 

PMID- 26214174
TI  - Effect of Sediment Gas Voids and Ebullition on Benthic Solute Exchange.
AB  - The presence of free gas in sediments and ebullition events can enhance the pore
      water transport and solute exchange across the sediment-water interface. However,
      we experimentally and theoretically document that the presence of free gas in
      sediments can counteract this enhancement effect. The apparent diffusivities (Da)
      of Rhodamine WT and bromide in sediments containing 8-18% gas (Da,YE) were
      suppressed by 7-39% compared to the control (no gas) sediments (Da,C). The
      measured ratios of Da,YE:Da,C were well within the range of ratios predicted by a
      theoretical soil model for gas-bearing soils. Whereas gas voids in sediments
      reduce the Da for soluble species, they represent a shortcut for low-soluble
      species such as methane and oxygen. Therefore, the presence of even minor amounts
      of gas can increase the fluxes of low-soluble species (i.e., gases) by several
      factors, while simultaneously suppressing fluxes of dissolved species. 

PMID- 26214176
TI  - Can Optimism, Pessimism, Hope, Treatment Credibility and Treatment Expectancy Be
      Distinguished in Patients Undergoing Total Hip and Total Knee Arthroplasty?
AB  - OBJECTIVES: The constructs optimism, pessimism, hope, treatment credibility and
      treatment expectancy are associated with outcomes of medical treatment. While
      these constructs are grounded in different theoretical models, they nonetheless
      show some conceptual overlap. The purpose of this study was to examine whether
      currently available measurement instruments for these constructs capture the
      conceptual differences between these constructs within a treatment setting.
      METHODS: Patients undergoing Total Hip and Total Knee Arthroplasty (THA and TKA)
      (Total N = 361; 182 THA; 179 TKA), completed the Life Orientation Test-Revised
      for optimism and pessimism, the Hope Scale, the Credibility Expectancy
      Questionnaire for treatment credibility and treatment expectancy. Confirmatory
      factor analysis was used to examine whether the instruments measure distinct
      constructs. Four theory-driven models with one, two, four and five latent factors
      were evaluated using multiple fit indices and Deltachi2 tests, followed by some
      posthoc models. RESULTS: The results of the theory driven confirmatory factor
      analysis showed that a five factor model in which all constructs loaded on
      separate factors yielded the most optimal and satisfactory fit. Posthoc, a
      bifactor model in which (besides the 5 separate factors) a general factor is
      hypothesized accounting for the commonality of the items showed a significantly
      better fit than the five factor model. All specific factors, except for the hope
      factor, showed to explain a substantial amount of variance beyond the general
      factor. CONCLUSION: Based on our primary analyses we conclude that optimism,
      pessimism, hope, treatment credibility and treatment expectancy are
      distinguishable in THA and TKA patients. Postdoc, we determined that all
      constructs, except hope, showed substantial specific variance, while also sharing
      some general variance.

PMID- 26214177
TI  - Tracking the History and Ecological Changes of Rising Double-Crested Cormorant
      Populations Using Pond Sediments from Islands in Eastern Lake Ontario.
AB  - In the Laurentian Great Lakes region, the double-crested cormorant (Phalacrocorax
      auritus) has seen a thousand-fold population increase in recent decades. These
      large colonies of birds now often conflict with socioeconomic interests,
      particularly due to perceived competition with fisheries and the destruction of
      terrestrial vegetation in nesting habitats. Here we use dated sediment cores from
      ponds on islands in eastern Lake Ontario that receive waste inputs from dense
      colonies of cormorants and ring-billed gulls (Larus delawarensis) to chronicle
      the population rise of these species and assess their long-term ecological
      impacts. Modern water chemistry sampling from these sites reveals drastically
      elevated nutrient and major ion concentrations compared to reference ponds not
      influenced by waterbirds. Geochemical tracers in dated sediment cores,
      particularly delta15N and chlorophyll-a concentrations, track waterbird
      influences over time. Fossil diatom assemblages were dominated by species
      tolerant of hyper-eutrophic and polluted systems, which is in marked contrast to
      assemblages in reference sites. In addition to establishing long-term ecological
      impacts, this multi-proxy paleoecological approach can be used to determine
      whether islands of concern have been long-term nesting sites or were only
      recently colonized by cormorant or ring-billed gull populations across the Great
      Lakes, facilitating informed management decisions about controversial culling
      programs. 

PMID- 26214178
TI  - Calibration and Validation of the Dutch-Flemish PROMIS Pain Interference Item
      Bank in Patients with Chronic Pain.
AB  - The Dutch-Flemish PROMIS Group translated the adult PROMIS Pain Interference item
      bank into Dutch-Flemish. The aims of the current study were to calibrate the
      parameters of these items using an item response theory (IRT) model, to evaluate
      the cross-cultural validity of the Dutch-Flemish translations compared to the
      original English items, and to evaluate their reliability and construct validity.
      The 40 items in the bank were completed by 1085 Dutch chronic pain patients.
      Before calibrating the items, IRT model assumptions were evaluated using
      confirmatory factor analysis (CFA). Items were calibrated using the graded
      response model (GRM), an IRT model appropriate for items with more than two
      response options. To evaluate cross-cultural validity, differential item
      functioning (DIF) for language (Dutch vs. English) was examined. Reliability was
      evaluated based on standard errors and Cronbach's alpha. To evaluate construct
      validity correlations with scores on legacy instruments (e.g., the Disabilities
      of the Arm, Shoulder and Hand Questionnaire) were calculated. Unidimensionality
      of the Dutch-Flemish PROMIS Pain Interference item bank was supported by CFA
      tests of model fit (CFI = 0.986, TLI = 0.986). Furthermore, the data fit the GRM
      and showed good coverage across the pain interference continuum (threshold
      parameters range: -3.04 to 3.44). The Dutch-Flemish PROMIS Pain Interference item
      bank has good cross-cultural validity (only two out of 40 items showing DIF),
      good reliability (Cronbach's alpha = 0.98), and good construct validity (Pearson
      correlations between 0.62 and 0.75). A computer adaptive test (CAT) and Dutch
      Flemish PROMIS short forms of the Dutch-Flemish PROMIS Pain Interference item
      bank can now be developed. 

PMID- 26214179
TI  - Planckian Power Spectral Densities from Human Calves during Posture Maintenance
      and Controlled Isometric Contractions.
AB  - BACKGROUND: The relationship between muscle anatomy and physiology and its
      corresponding electromyography activity (EMGA) is complex and not well
      understood. EMGA models may be broadly divided in stochastic and motor-unit-based
      models. For example, these models have successfully described many muscle
      physiological variables such as the value of the muscle fiber velocity and the
      linear relationship between median frequency and muscle fiber velocity. However
      they cannot explain the behavior of many of these variables with changes in
      intramuscular temperature, or muscle PH acidity, for instance. Here, we propose
      that the motor unit action potential can be treated as an electromagnetic
      resonant mode confined at thermal equilibrium inside the muscle. The motor units
      comprising the muscle form a system of standing waves or modes, where the energy
      of each mode is proportional to its frequency. Therefore, the power spectral
      density of the EMGA is well described and fit by Planck's law and from its
      distribution we developed theoretical relationships that explain the behavior of
      known physiological variables with changes in intramuscular temperature or muscle
      PH acidity, for instance. METHODS: EMGA of the calf muscle was recorded during
      posture maintenance in seven participants and during controlled isometric
      contractions in two participants. The power spectral density of the EMGA was then
      fit with the Planckian distribution. Then, we inferred nine theoretical
      relationships from the distribution and compared the theoretically derived values
      with experimentally obtained values. RESULTS: The power spectral density of EMGA
      was fit by Planckian distributions and all the theoretical relationships were
      validated by experimental results. CONCLUSIONS: Only by considering the motor
      unit action potentials as electromagnetic resonant modes confined at thermal
      equilibrium inside the muscle suffices to predict known or new theoretical
      relationships for muscle physiological variables that other models have failed to
      do.

PMID- 26214181
TI  - Physical properties of the hybrid lipid POPC on micrometer-sized domains in mixed
      lipid membranes.
AB  - Macro-phase separation in mixed lipid membranes containing the hybrid lipid
      palmitoyloleoylphosphatidylcholine (POPC) was observed by fluorescent and
      confocal laser scanning microscopy. In a binary system consisting of the
      saturated lipid dipalmitoylphosphatidylcholine (DPPC) and the hybrid lipid POPC,
      the hybrid lipid forms a liquid-disordered (Ld) phase. In a ternary system
      consisting of this binary system and an unsaturated lipid
      dioleoylphosphatidylcholine (DOPC), three-phase coexistence is observed. The POPC
      rich phase appears around DPPC-rich domains, and the hybrid lipid is expected to
      behave like a line-active agent (linactant). Finally, phase separation in a four
      component system, composed of this ternary system and cholesterol, was examined.
      Domains with a size that is smaller than 1 MUm are found, and domain-induced
      budding is also observed. To explain small domain formation and domain-induced
      budding, chain ordering was evaluated based on Laurdan generalized polarization
      measurements. Our observations revealed that the hybrid lipid acted like a
      linactant to solid domains and disturbed chain ordering in liquid-ordered (Lo)
      domains. In both cases, the hybrid lipid reduced line tension at the domain
      boundary. 

PMID- 26214180
TI  - Predictive Ability of Laboratory Indices for Liver Fibrosis in Patients with
      Chronic Hepatitis C after the Eradication of Hepatitis C Virus.
AB  - Liver fibrosis remains an important risk factor for hepatocarcinogenesis in
      patients with chronic hepatitis C even after the eradication of hepatitis C virus
      (HCV). However, it is difficult to estimate liver fibrosis based on liver biopsy
      after the eradication of HCV. We investigated the ability of laboratory indices
      to predict liver fibrosis in patients with sustained virologic response (SVR) to
      antiviral therapy. Three laboratory liver fibrosis indices (aspartate
      aminotransferase-platelet ratio index (APRI), FIB-4 index, and Forns index) were
      calculated based on data at the time of initial pretreatment liver biopsy and at
      second liver biopsy performed approximately 5 years after SVR in 115 patients who
      underwent serial liver biopsies. The indices at the time of initial biopsy were
      compared to histological degree of liver fibrosis in initial biopsy, and
      laboratory indices at the time of second liver biopsy were compared to the degree
      of fibrosis in second biopsy. In both comparisons, there were significant
      increases in all 3 indices with the increase of liver fibrosis grade as assessed
      in liver biopsy specimens. All 3 indices at the time of second biopsy were able
      to predict moderate to advanced (METAVIR score F2-4) and advanced (F3-4) fibrosis
      on liver biopsy, with the area under the receiver-operating characteristics curve
      >0.8 and the accuracy >70%. All 3 laboratory indices of fibrosis accurately
      reflected liver fibrosis in patients with SVR for 5 years despite the
      normalization of serum liver transaminase activity and the lack of liver
      inflammation. 

PMID- 26214182
TI  - Extracting Environmental Benefits from a New Canal in Nicaragua: Lessons from
      Panama.
AB  - Biologists have raised objections to a new canal in Nicaragua, but in this Essay
      I argue that dire predictions of environmental catastrophe are exaggerated. I
      present an alternative view based on my research experience in Panama, where
      Canal operations foster forest conservation. Currently in Nicaragua, the rate of
      forest loss is so rapid that the canal cannot make it worse. Rather, I contend,
      adoption of international standards in canal construction could lead to net
      environmental and social benefits for the country. 

PMID- 26214183
TI  - Prevalence and Impact of Sleep Disordered Breathing in Patients with Severe
      Aortic Stenosis.
AB  - BACKGROUND: Unlike the well-established association between sleep disordered
      breathing (SDB) and chronic heart failure, the relationship between SDB and
      severe aortic stenosis (AS) is not well investigated. Given the increasing
      prevalence of AS, and the improving prognosis of high risk AS patients
      attributable to transcatheter aortic valve implantation (TAVI), the prevalence
      and impact of SDB needs to be better understood. METHODS AND RESULTS: In this
      study, 140 patients with severe AS underwent polygraphy prior to TAVI. Clinical
      and hemodynamic parameters were recorded. Patients were followed for 573+/-405
      days. We found that 99/140 patients (71%) had SDB with a mean apnoea-hypopnoea
      index of 24+/-17/h. SDB was mild in 27%, moderate in 23% and severe in 21% of
      patients. In addition, 35 patients (25%) had obstructive sleep apnoea (OSA),
      whereas 64 patients (46%) had central sleep apnoea (CSA). Patients with OSA had
      predominantly mild SDB (20/38 pts.), and patients with CSA mostly had severe SDB
      (24/29 pts.). The prevalence and distribution of OSA and CSA were independent of
      left ventricular function. Overall, 1 and 2 year survival rates (74% and 71%,
      resp.) did not differ significantly between patients without SDB or those with
      OSA and CSA (p=0.81). CONCLUSIONS: SDB, with a preponderance of CSA, was found to
      be highly prevalent in patients with high-grade AS scheduled for TAVI. SDB
      prevalence was independent of left ventricular function. Mortality after TAVI was
      not influenced by the type or severity of SDB.

PMID- 26214184
TI  - Improving lifestyle interventions for people with serious mental illnesses:
      Qualitative results from the STRIDE study.
AB  - OBJECTIVE: Individuals with serious mental illnesses are disproportionately
      affected by overweight and obesity. Understanding the factors that facilitate or
      hinder lifestyle change in this population could lead to better interventions and
      improved health outcomes. METHODS: A subset of intervention and usual-care
      participants (n = 84) in the STRIDE randomized trial were interviewed at 3, 9,
      and 18 months, yielding 101 interviews (some were interviewed more than once).
      Participants had a mean age of 48.1 (SD = 10.1); 64% were female. Participants
      had diagnoses of schizophrenia or schizoaffective disorder (41%), bipolar
      disorder (20%), affective psychoses (37%), or PTSD (2%). Interviews were
      transcribed verbatim, coded using Atlas.ti, and analyzed for common themes.
      RESULTS: Barriers to behavior change were similar to those described for the
      general population, including lack of support from significant others, the lure
      of unhealthy foods, and poor weather impeding exercise. Additional challenges
      included the effects of psychiatric symptoms, or consequences of symptoms (i.e.,
      social isolation), on ability to make and sustain lifestyle changes. We found a
      strong preference for ongoing, group-based support to foster a sense of
      accountability which motivated and helped to sustain behavior changes.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Individuals with serious mental
      illnesses encounter many of the same barriers to weight loss seen in the general
      population, but they may be more vulnerable to additional obstacles. Lifestyle
      change interventions for this population should help participants develop the
      ability to iteratively cope with fluctuating mood and subsequent changes in
      motivation to eat healthfully and exercise regularly.

PMID- 26214185
TI  - The Stability of Ribosome Biogenesis Factor WBSCR22 Is Regulated by Interaction
      with TRMT112 via Ubiquitin-Proteasome Pathway.
AB  - The human WBSCR22 protein is a 18S rRNA methyltransferase involved in pre-rRNA
      processing and ribosome 40S subunit biogenesis. Recent studies have shown that
      the protein function in ribosome synthesis is independent of its enzymatic
      activity. In this work, we have studied the WBSCR22 protein interaction partners
      by SILAC-coupled co-immunoprecipitation assay and identified TRMT112 as the
      interaction partner of WBSCR22. Knock-down of TRMT112 expression decreased the
      WBSCR22 protein level in mammalian cells, suggesting that the stability of
      WBSCR22 is regulated through the interaction with TRMT112. The localization of
      the TRMT112 protein is determined by WBSCR22, and the WBSCR22-TRMT112 complex is
      localized in the cell nucleus. We provide evidence that the interaction between
      WBSCR22/Bud23 and TRMT112/Trm112 is conserved between mammals and yeast,
      suggesting that the function of TRMT112 as a co-activator of methyltransferases
      is evolutionarily conserved. Finally, we show that the transiently expressed
      WBSCR22 protein is ubiquitinated and degraded through the proteasome pathway,
      revealing the tight control of the WBSCR22 protein level in the cells. 

PMID- 26214187
TI  - Polymeric 3D nano-architectures for transport and delivery of therapeutically
      relevant biomacromolecules.
AB  - A promising approach for addressing a range of diseases lies in the delivery of
      functional biomacromolecules such as nucleic acids or proteins to cells.
      Polymers, peptides and the different shapes accessible through self-assembly of
      polymeric and peptidic amphiphiles have been widely explored as carriers and as
      containers for reactions on the nanoscale. These building blocks are particularly
      interesting, because several essential parameters such as physical
      characteristics, conditions for degradation or biocompatibility can be tuned to
      suit specific requirements. In this review, different three-dimensional
      architectures ranging from dendrimers and hyperbranched molecules to micelles,
      vesicles and nanoparticles assembled from synthetic polymers and peptides are
      discussed. It is focused on their function as a carrier for biologically active
      macromolecules, highlighting seminal examples from the current literature and
      pointing out the remaining and upcoming challenges in this important area of
      research. 

PMID- 26214189
TI  - Cancer-targeted near infrared imaging using rare earth ion-doped ceramic
      nanoparticles.
AB  - The use of near-infrared (NIR) light over 1000 nm (OTN-NIR or second NIR) is
      advantageous for bioimaging because it enables deep tissue penetration due to low
      scattering and autofluorescence. In this report, we describe the application of
      rare earth ion-doped ceramic nanoparticles to cancer-targeted NIR imaging using
      erbium and ytterbium ion-doped yttrium oxide nanoparticles (YNP) functionalized
      with streptavidin via bi-functional PEG (SA-YNP). YNP has NIR emission at 1550
      nm, with NIR excitation at 980 nm (NIR-NIR imaging). Cancer-specific NIR-NIR
      imaging was demonstrated using SA-YNP and biotinylated antibodies on cancer cells
      and human colon cancer tissues. NIR-NIR imaging through porcine meat of 1 cm
      thickness was also demonstrated, supporting the possible application of deep
      tissue NIR-NIR bioimaging using YNP as a probe. Our results suggest that non
      invasive imaging using YNP has great potential for general application in cancer
      imaging in living subjects. 

PMID- 26214188
TI  - Elastomeric nanocomposite scaffolds made from poly(glycerol sebacate) chemically
      crosslinked with carbon nanotubes.
AB  - Carbon nanotube (CNT)-based nanocomposites often possess properties such as high
      stiffness, electrical conductivity, and thermal stability and have been studied
      for various biomedical and biotechnological applications. However, the current
      design approaches utilize CNTs as physical fillers, and thus, the true potential
      of CNT-based nanocomposites has not been realized. Here, we introduce a general
      approach to fabricating stiff, elastomeric nanocomposites from poly(glycerol
      sebacate) (PGS) and CNTs. The covalent crosslinking between the nanotubes and
      polymer chains resulted in novel property combinations that are not observed in
      conventional nanocomposites. The addition of 1% CNTs resulted in a five-fold
      increase in the tensile modulus and a six-fold increase in compression modulus
      compared with PGS alone, which is far superior to the previously reported studies
      for CNT-based nanocomposites. Despite a significant increase in mechanical
      stiffness, the elasticity of the network was not compromised and the resulting
      nanocomposites showed more than 94% recovery. This study demonstrates that the
      chemical conjugation of CNTs to a PGS backbone results in stiff and elastomeric
      nanocomposites. Additionally, in vitro studies using human mesenchymal stem cells
      (hMSCs) indicated that the incorporation of CNTs into the PGS network
      significantly enhanced the differentiation potential of the seeded hMSCs,
      rendering them potentially suitable for applications ranging from scaffolding in
      musculoskeletal tissue engineering to biosensors in biomedical devices. 

PMID- 26214190
TI  - Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord.
AB  - Spinal cord injury is a debilitating condition that currently lacks effective
      clinical treatment. Neurotrophin-3 (NT-3) has been demonstrated in experimental
      animal models to induce axonal regeneration and functional improvements, yet its
      local delivery remains challenging. For ultimate clinical translation, a drug
      delivery system is required for localized, sustained, and minimally invasive
      release. Here, an injectable composite drug delivery system (DDS) composed of
      biodegradable polymeric nanoparticles dispersed in a hyaluronan/methyl cellulose
      hydrogel was injected into the intrathecal space to achieve acute local delivery
      to the spinal cord after a thoracic clip compression injury. NT-3 was
      encapsulated in the DDS and released in vitro for up to 50 d. With a single
      injection of the DDS into the intrathecal space of the injured spinal cord, NT-3
      diffused ventrally through the cord and was detectable in the spinal cord for at
      least 28 d therein. Delivery of NT-3 resulted in significant axon growth with no
      effect on the astroglial response to injury in comparison with vehicle and injury
      controls. NT-3 treatment promoted functional improvements at 21 d according to
      the Basso Beattie Bresnahan locomotor scale in comparison with the DDS alone. The
      sustained delivery of bioactive NT-3 to the injured spinal cord achieved in this
      study demonstrates the promise of this DDS for central nervous system repair. 

PMID- 26214191
TI  - Heparin-induced conformational changes of fibronectin within the extracellular
      matrix promote hMSC osteogenic differentiation.
AB  - An increasing body of evidence suggests important roles of extracellular matrix
      (ECM) in regulating stem cell fate. This knowledge can be exploited in tissue
      engineering applications for the design of ECM scaffolds appropriate to direct
      stem cell differentiation. By probing the conformation of fibronectin (Fn) using
      fluorescence resonance energy transfer (FRET), we show here that heparin
      treatment of the fibroblast-derived ECM scaffolds resulted in more extended
      conformations of fibrillar Fn in ECM. Since heparin is a highly negatively
      charged molecule while fibronectin contains segments of positively charged
      modules, including FnIII13, electrostatic interactions between Fn and heparin
      might interfere with residual quaternary structure in relaxed fibronectin fibers
      thereby opening up buried sites. The conformation of modules FnIII12-14 in
      particular, which contain one of the heparin binding sites as well as binding
      sites for many growth factors, may be activated by heparin, resulting in
      alterations in growth factor binding to Fn. Indeed, upregulated osteogenic
      differentiation was observed when hMSCs were seeded on ECM scaffolds that had
      been treated with heparin and were subsequently chemically fixed. In contrast,
      either rigidifying relaxed fibers by fixation alone, or heparin treatment without
      fixation had no effect. We hypothesize that fibronectin's conformations within
      the ECM are activated by heparin such as to coordinate with other factors to
      upregulate hMSC osteogenic differentiation. Thus, the conformational changes of
      fibronectin within the ECM could serve as a 'converter' to tune hMSC
      differentiation in extracellular matrices. This knowledge could also be exploited
      to promote osteogenic stem cell differentiation on biomedical surfaces. 

PMID- 26214192
TI  - Biomimetic honeycomb-patterned surface as the tunable cell adhesion scaffold.
AB  - Inspired by the typically adhesive behaviors of fish skin and Parthenocissus
      tricuspidata, two different decorations of polystyrene honeycomb membrane (PSHCM)
      prepared by the breath figure approach were carried out with poly(N-(3
      Sulfopropyl)-N-(methacryloxyethyl)-N,N-dimethylammonium betaine)(polySBMA) to
      explore controllable bioadhesive surfaces. Casting and dip-coating were employed
      to graft polySBMA onto the plasma treated PSHCM. The polySBMA casted PSHCM showed
      a uniform covering layer on the PSHCM similar to the mucus layer of fish skin,
      presenting excellent antifouling properties. On the contrary, a dip-coated one
      showed the polySBMA aggregating on the honeycomb pore walls forming a large
      number of sucking disks such as the adhesive disks of the tendrils of P.
      tricuspidata, which remarkably boosts cell adhesion on substrates. Thus,
      bioadhesion could be regulated as desired by tuning the distribution of
      zwitterionic polymer on the honeycomb surface. The results may provide a new
      approach for the design of biomaterial surfaces. 

PMID- 26214193
TI  - Patterning of supported lipid bilayers and proteins using material selective
      nitrodopamine-mPEG.
AB  - We present a generic patterning process by which biomolecules in a passivated
      background are patterned directly from physiological buffer to microfabricated
      surfaces without the need for further processing. First, nitrodopamine-mPEG is
      self-assembled to selectively render TiO2 patterns non-fouling to biomolecule
      adsorption on hydrophilic and adhesive glass surfaces. After the controlled TiO2
      passivation, the biomolecules can be directly adsorbed from solution in a single
      step creating large scale micropatterned and highly homogeneous arrays of
      biomolecules with very high pattern definition. We demonstrate the formation of
      fluid supported lipid bilayers (SLBs) down to the single MUm-level limited only
      by the photolithographic process. Non-specific adsorption of lipid vesicles to
      the TiO2 background was found to be almost completely suppressed. The SLB
      patterns can be further selectively functionalized with retained mobility, which
      we demonstrate through biotin-streptavidin coupling. We envision this single step
      patterning approach to be very beneficial for membrane-based biosensors and for
      pattering of cells on a passivated background with complex, sub-cellular
      geometries; in each application the adherent areas have a tunable mobility of
      interaction sites controlled by the fluidity of the membrane. 

PMID- 26214194
TI  - Targeted delivery of a novel anticancer compound anisomelic acid using chitosan
      coated porous silica nanorods for enhancing the apoptotic effect.
AB  - Targeted cancer therapies are currently a strong focus in biomedical research.
      The most common approach is to use nanocarrier-based targeting to specifically
      deliver conventional anticancer drugs to enhance their therapeutic efficacy,
      increase bioavailability, and decrease the side-effects on normal cells. A step
      further towards higher specificity and efficacy would be to employ specific novel
      drugs along with specific nanocarrier-based targeting. Our recent studies have
      demonstrated that a plant-derived diterpenoid compound, anisomelic acid (AA),
      induces apoptosis in cervical cancer cells. In this work, we describe the
      development of a folic acid (FA)-targeted AA delivery system using chitosan
      coated rod-shaped mesoporous silica particles (Chitosan-NR-MSP). The cellular
      internalization and uptake enhancement of the FA-Chitosan-NR-MSP towards
      cancerous folate receptor (FR)-positive (SiHa and HeLa) and/or normal FR-negative
      (HEK 293) cells were assessed, which indicated that the intracellular uptake of
      FA-conjugated Chitosan-NR-MSP was more target-specific. Furthermore, the
      induction of apoptosis by AA-loaded chitosan-coated rod-shaped particles on SiHa
      cells was studied. By employing caspase-3 activation and PARP cleavage as measure
      of apoptosis, the FA-particle mediated AA treatment was clearly more effective,
      significantly enhancing apoptosis in comparison to non-targeted Chitosan-NR-MSP
      or free AA in SiHa cells, suggesting that the FA-Chitosan-NR-MSPs can be
      potentially utilized as a drug delivery system for cervical cancer treatment. 

PMID- 26214195
TI  - Reducible, dibromomaleimide-linked polymers for gene delivery.
AB  - Polycations have been successfully used as gene transfer vehicles both in vitro
      and in vivo; however, their cytotoxicity has been associated with increasing
      molecular weight. Polymers that can be rapidly degraded after internalization are
      typically better tolerated by mammalian cells compared to their non-degradable
      counterparts. Here, we report the use of a dibromomaleimide-alkyne (DBM-alkyne)
      linking agent to reversibly bridge cationic polymer segments for gene delivery
      and to provide site-specific functionalization by azide-alkyne cycloaddition
      chemistry. A panel of reducible and non-reducible, statistical copolymers of (2
      dimethylamino)ethyl methacrylate (DMAEMA) and oligo(ethylene glycol)methyl ether
      methacrylate (OEGMA) were synthesized and evaluated. When complexed with plasmid
      DNA, the reducible and non-reducible polymers had comparable DNA condensation
      properties, sizes, and transfection efficiencies. When comparing cytotoxicity,
      the DBM-linked, reducible polymers were significantly less toxic than the non
      reducible polymers. To demonstrate polymer functionalization by click chemistry,
      the DBM-linked polymers were tagged with an azide-fluorophore and were used to
      monitor cellular uptake. Overall, this polymer system introduces the use of a
      reversible linker, DBM-alkyne, to the area of gene delivery and allows for
      facile, orthogonal, and site-specific functionalization of gene delivery
      vehicles. 

PMID- 26214196
TI  - Topographically grooved gel inserts for aligning epithelial cells during air
      liquid-interface culture.
AB  - Epithelial tissues are a critical component of all tubular organs. Engineering
      artificial epithelium requires an understanding of the polarization of epithelia:
      both apicobasal and in a planar fashion. Air liquid interface (ALI) culture is
      typically used to generate apicobasal polarized airway epithelium in vitro;
      however, this approach does not provide any signalling cues to induce
      morphological planar polarization of the generated epithelial layer. Here we
      describe a microgrooved gelatin hydrogel insert that can induce alignment of
      confluent epithelial cell sheets under ALI conditions to induce both apicobasal
      and morphologically planar polarized epithelium. Microgrooves are imprinted into
      the surface of the gelatin insert using elastomeric stamps moulded from a
      diffraction grating film and gels are stabilized by crosslinking with
      glutaraldehyde. We show that microgrooved gelatin inserts produce alignment of
      3T3 fibroblasts and a number of epithelial cell lines (ARPE-19, BEAS2B and IMCD3
      cells). Furthermore, we show that BEAS2B apicobasally polarize and form a similar
      density of cilia on both gelatin inserts and standard transwell filters used for
      ALI culture but that as apicobasal polarization progresses cell alignment on the
      grooves is lost. Our method provides a simple strategy that can easily be adopted
      by labs without microfabrication expertise for manipulating epithelial
      organization in transwell culture and studying the interplay of various
      polarization forces. 

PMID- 26214197
TI  - mRNA delivery using non-viral PCL nanoparticles.
AB  - Messenger RNA (mRNA) provides a promising alternative to plasmid DNA as a genetic
      material for delivery in non-viral gene therapy strategies. However, it is
      difficult to introduce mRNA in vivo mainly because of the instability of mRNA
      under physiological conditions. Here, mRNA-protamine complex encapsulated
      poly(epsilon-caprolactone) (PCL) nanoparticles (NPs) are proposed for the
      intracellular delivery of mRNA molecules. The nanoparticles with a size of about
      247 nm in diameter have a core-shell structure with an mRNA-containing inner core
      surrounded by PCL layers, providing high stability and stealth properties to the
      nanoparticles. The partial neutralization of the negatively charged mRNA
      molecules with the cationic protamine allows one to modulate the release kinetics
      in a pH-dependent manner. At pH 7.4, mimicking the conditions found in the
      systemic circulation, only 25% of the mRNA is released after 48 hours post
      incubation, whereas at pH 5.0, recreating the cell endosomal environment, about
      60% of the mRNA molecules are released within the same time window post
      incubation. These NPs show no cytotoxicity to NIH 3T3 fibroblasts, HeLa cells and
      MG63 osteoblasts up to 8 days of incubation. Given the stability, preferential
      release behavior, and well-known biocompatibility properties of PCL
      nanostructures, our non-viral PCL nanoparticles are a promising system that
      simultaneously resolved the two major problems of mRNA introduction and the
      instability, opening the door to various new therapeutic strategies using mRNA. 

PMID- 26214198
TI  - pH and glucose responsive nanofibers for the reversible capture and release of
      lectins.
AB  - A dual pH and glucose responsive boronic acid containing nanofiber was
      constructed for the reversible capture and release of lectins. The effects of
      surface groups and pH values on selective lectin capture were investigated by
      fluorescence microscopy. Compared to the pristine nanofibrous membrane, glucose
      and galactose functionalized nanofiber surfaces showed significantly higher
      capture of ConA and Jacalin, under alkaline conditions. On the other hand,
      treatment of the modified nanofibers with an acidic solution resulted in the
      detachment of both the lectins and glycopolymers from the nanofiber surface. As
      expected, once the glycopolymers are displaced, no lectins were adhered to the
      nanofiber surface under alkaline conditions. These functional nanofibers can
      therefore be easily modified and hence can be used for quick removal of selective
      proteins or toxins from the solution. 

PMID- 26214199
TI  - Dual-drug delivery of curcumin and platinum drugs in polymeric micelles enhances
      the synergistic effects: a double act for the treatment of multidrug-resistant
      cancer.
AB  - Combinational chemotherapy is often used to prevent drug induced resistance in
      cancer. The aim of this work is to test whether the co-delivery of drugs within
      one nanoparticle can result in increased synergistic effects of both drugs.
      Therefore, a micelle system with two different compartments, one for the drug
      curcumin and one for the conjugation of platinum drugs was designed. A triblock
      copolymer, based on the biodegradable polycaprolactone PCL, a PEG based shell and
      an amine bearing polymer as the interphase for the conjugation of platinum drugs
      was prepared by combination of ring-opening polymerization and RAFT
      polymerization. Curcumin was incorporated into the self-assembled onion-type
      micelle by physical encapsulation into the PCL core with an entrapment capacity
      of 6 wt%. The platinum(iv) drug oxoplatin was reacted with succinic anhydride to
      yield Pt(NH3)2Cl2[(COOH)2], which acted as the drug and as a crosslinker for the
      stabilisation of micelles. The size of the dual drug micelles was measured to be
      38 nm by DLS, which was confirmed by TEM. The toxicity of the dual drug delivery
      system was tested against the A2780 human ovarian cancer cell line and compared
      with the IC50 value of micelles that deliver either curcumin or the platinum drug
      alone. The results were analysed using the CalcuSyn software. While curcumin and
      the platinum drug together without a carrier already showed synergy with a
      combination index ranging from 0.4 to 0.8, the combined delivery in one
      nanoparticle did enhance the synergistic effects resulting in a combination index
      of approximately 0.2-0.35. For comparison, a mixture of two nanoparticles, one
      with curcumin and the other with the platinum drug, was tested revealing a less
      noticeable synergistic effect compared to the co-delivery of both drugs in one
      drug carrier. 

PMID- 26214200
TI  - Thiol-ene immobilisation of carbohydrates onto glass slides as a simple
      alternative to gold-thiol monolayers, amines or lipid binding.
AB  - Carbohydrate arrays are a vital tool in studying infection, probing the
      mechanisms of bacterial, viral and toxin adhesion and the development of new
      treatments, by mimicking the structure of the glycocalyx. Current methods rely on
      the formation of monolayers of carbohydrates that have been chemically modified
      with a linker to enable interaction with a functionalised surface. This includes
      amines, biotin, lipids or thiols. Thiol-addition to gold to form self-assembled
      monolayers is perhaps the simplest method for immobilisation as thiolated glycans
      are readily accessible from reducing carbohydrates in a single step, but are
      limited to gold surfaces. Here we have developed a quick and versatile
      methodology which enables the use of thiolated carbohydrates to be immobilised as
      monolayers directly onto acrylate-functional glass slides via a 'thiol
      ene'/Michael-type reaction. By combining the ease of thiol chemistry with glass
      slides, which are compatible with microarray scanners this offers a cost
      effective, but also useful method to assemble arrays. 

PMID- 26214175
TI  - The Effect of Incidental Consolidation on Management and Outcomes in COPD
      Exacerbations: Data from the European COPD Audit.
AB  - OBJECTIVE: There is controversy regarding the significance of radiological
      consolidation in the context of COPD exacerbation (eCOPD). While some studies
      into eCOPD exclude these cases, consolidation is a common feature of eCOPD
      admissions in real practice. This study aims to address the question of whether
      consolidation in eCOPD is a distinct clinical phenotype with implications for
      management decisions and outcomes. PATIENTS AND METHODS: The European COPD Audit
      was carried out in 384 hospitals from 13 European countries between 2010 and 2011
      to analyze guideline adherence in eCOPD. In this analysis, admissions were split
      according to the presence or not of consolidation on the admission chest
      radiograph. Groups were compared in terms of clinical and epidemiological
      features, existing treatment, clinical care utilized and mortality. RESULTS:
      14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397
      (80.8%) without. The risk of radiographic consolidation increased with age,
      female gender, cardiovascular diseases, having had two or more admissions in the
      previous year, and sputum color change. Previous treatment with inhaled steroids
      was not associated. Patients with radiographic consolidation were significantly
      more likely to receive antibiotics, oxygen and non-invasive ventilation during
      the admission and had a lower survival from admission to 90-day follow-up.
      CONCLUSIONS: Patients admitted for COPD exacerbation who have radiological
      consolidation have a more severe illness course, are treated more intensively by
      clinicians and have a poorer prognosis. We recommend that these patients be
      considered a distinct subset in COPD exacerbation.

PMID- 26214201
TI  - Overcoming tumor resistance to cisplatin through micelle-mediated combination
      chemotherapy.
AB  - The main obstacles to cancer therapy are the inability to target cancer cells and
      the acquired drug resistance after a period of chemotherapy. Reduced drug uptake
      and DNA repair are the two main mechanisms involved in cisplatin resistance. In
      the present investigation, canthaplatin, a Pt(iv) pro-drug of cisplatin and a
      protein phosphatase 2A (PP2A) inhibitor (4-(3-carboxy-7-oxa-bicyclo[2.2.1]heptane
      2-carbonyl)piperazine-1-carboxylic acid tert-butyl ester), was designed and
      delivered using PEG-b-PLGA micelles for combination chemotherapy.
      Polymer/canthaplatin micelles facilitated the delivery of the drug into cancer
      cells through endocytosis and diminished DNA repair by PP2A inhibition, resulting
      in enhanced anti-tumor efficiency and excellent reversal ability of tumor
      resistance to cisplatin both in vitro and in vivo. Additionally, the
      polymer/canthaplatin micelles could prolong drug residence in the blood and
      decrease the side effects when compared to cisplatin. 

PMID- 26214203
TI  - Warfarin Discontinuation in Patients With Unprovoked Venous Thromboembolism: A
      Large US Insurance Database Analysis.
AB  - This study examined warfarin therapy discontinuation and its risk factors among
      patients with unprovoked venous thromboembolism (VTE) in the US clinical practice
      setting. Adult patients with unprovoked VTE were identified from the MarketScan
      claims database from January 1, 2006 to December 31, 2012. The index date was
      defined as the date of first VTE diagnosis. Patients were required to have no VTE
      diagnosis in the 6 months before index date and continuous health plan enrollment
      for 6 months before and 12 months after the index date. Warfarin discontinuation
      rates and adjusted hazard ratios (HRs) were reported. Of 21,163 eligible
      patients, 15,463 were diagnosed with deep vein thrombosis (DVT) only (73.1%),
      5027 with pulmonary embolism (PE) only (23.7%), and 673 with DVT and PE (3.2%).
      The average duration of warfarin therapy was 5.2 months (SD = 3.0). During 1-year
      follow-up, 21.4% patients discontinued therapy within 3 months, 42.8% within 6
      months, and 70.1% within 12 months. PE versus DVT [HR = 0.77, 95% confidence
      interval (CI) = 0.74-0.80], comorbid atrial fibrillation (HR = 0.73, 95% CI =
      0.66-0.81), thrombophilia (HR = 0.62, 95% CI = 0.54-0.71), and age >40 years (41
      65 years: HR = 0.86, 95% CI = 0.81-0.91; >65 years: HR = 0.82, 95% CI = 0.77
      0.87) were significantly associated with reduced risk of warfarin
      discontinuation. Alcohol abuse/dependence (HR = 1.36, 95% CI = 1.20-1.55), cancer
      history (HR = 1.13, 95% CI = 1.07-1.19), bleeding (HR = 1.07, 95% CI = 1.01
      1.15), and catheter ablation (HR = 1.10, 95% CI = 1.00-1.20) in the 6 months
      before index date were significantly associated with increased risk for warfarin
      discontinuation. In conclusion, nearly 1 of 4 patients with unprovoked VTE
      discontinued warfarin within 3 months. Three of 4 patients discontinued therapy
      within 1 year. Younger age and multiple clinical factors are associated with
      warfarin therapy discontinuation.

PMID- 26214202
TI  - Assembling Mn:ZnSe quantum dots-siRNA nanoplexes for gene silencing in tumor
      cells.
AB  - In this work, we demonstrate the use of manganese doped zinc selenide QDs
      (Mn:ZnSe d-dots) for gene delivery in vitro. Specifically, the d-dots were
      prepared as nanoplexes for facilitating the intracellular delivery of small
      interfering RNA (siRNA) molecules to pancreatic cancer cells (Panc-1), thereby
      inducing sequence-specific silencing of oncogenic K-Ras mutations in pancreatic
      carcinoma. For nanoplex preparation, a layer-by-layer (LBL) assembling method was
      adopted to modify the d-dot surface with cationic polymer poly(allylamine
      hydrochloride) (PAH) or polyethylenimine (PEI) for generating positive surface
      potential for complexing with K-Ras siRNA molecules. Owing to the unique and
      stable PL properties of the d-dots, siRNA transfection and the subsequent
      intracellular release profile from the d-dot/polymer-siRNA nanoplexes were
      monitored by fluorescence imaging. Quantitative results from flow cytometry study
      suggested that a high gene transfection efficiency was achieved. The expression
      of the mutant K-Ras mRNA in Panc-1 cells was observed to be significantly
      suppressed upon transfecting them with the nanoplex formulation. More
      importantly, cell viability studies showed that the d-dot/PAH nanoplexes were
      biocompatible and non-toxic even at concentrations as high as 160 MUg mL(-1).
      Furthermore, the amine-terminated surface could be further modified to obtain
      multiple bio-functions. Based on these results, we envision that the designed d
      dot nanoplexes can be developed as a flexible nanoplatform for both fundamental
      and practical clinical research applications. 

PMID- 26214204
TI  - Fogarty Maneuver to Restore Coronary Flow in ST-Segment Elevation Myocardial
      Infarction: Desperate Times Call for Desperate Measures.
AB  - Nonatherosclerotic embolism is a rare cause (4%-7%) of coronary occlusion in ST
      segment elevation myocardial infarction (STEMI) patients, approximately half of
      which occur in inadequately anticoagulated patients with prosthetic valves. We
      report a rare case of a patient with severe rheumatic heart disease and 3
      mechanical valves presenting with STEMI that was successfully managed by Fogarty
      maneuver thrombus extraction after failed thrombus aspiration and balloon
      angioplasty. A 56-year-old woman presented with an acute anterior STEMI and
      Killip class III heart failure. She had severe rheumatic heart disease with
      mechanical tricuspid, mitral and aortic valve prostheses, and atrial fibrillation
      on warfarin anticoagulation. The international normalized ratio on admission was
      1.1. Emergency coronary angiography revealed normal right and circumflex coronary
      arteries and a total occlusion in the mid left anterior descending artery with a
      meniscus appearance. Multiple attempts at thrombus aspiration and balloon
      angioplasty failed to restore flow in the left anterior descending artery.
      Ultimately, a Fogarty maneuver using a compliant balloon inflated at a low
      pressure was performed successfully, removing the thrombus into the guiding
      catheter. There was Thrombolysis in Myocardial Infarction flow grade 3 and near
      normal myocardial blush at the end of the procedure. Signs and symptoms of heart
      failure resolved quickly. 

PMID- 26214206
TI  - Magnetic structure of the ferromagnetic Kondo-lattice compounds YbPtGe and
      YbPdGe.
AB  - YbPtGe and YbPdGe exhibit ferromagnetic ordering below Tc = 5.4 and 11.4 K with
      enhanced electronic specific heat coefficients of gamma = 209 and 150 mJ K(-2)
      mol, respectively. In order to shed light on the origin of the coexistence of a
      ferromagnetic state and heavy-fermion behavior, we studied the powder neutron
      diffraction of YbPtGe and YbPdGe at low temperatures. Weak reflections due to
      magnetic ordering have been resolved. The data were analyzed using the Rietveld
      method together with group theory analysis. It has been found that YbPtGe
      exhibits a non-collinear ferromagnetic structure, with a spontaneous moment along
      the c-axis and a weak antiferromagnetic component along the a-axis. The presence
      of this antiferromagnetic component explains the origin of the observed
      metamagnetic-like behavior. In the case of YbPdGe, magnetization measurements
      confirmed the ferromagnetic moment along the b-axis and revealed a metamagnetic
      transition at 0.2 T for a field parallel to the c-axis. The neutron diffraction
      results indicate that the magnetic structure of YbPdGe is also of a non-collinear
      type, with ferromagnetic moments parallel to the b-axis and weak
      antiferromagnetic components along the c-axis, which is consistent with the
      magnetization data. A comparison of the results for YbPtGe and YbPdGe has been
      made. It is suggested that both the Kondo screening effect of ferromagnetic
      moments and the fluctuation of antiferromagnetic components can contribute to the
      enhanced mass in the ferromagnetic state.

PMID- 26214205
TI  - Perioperative Management of Anticoagulation-Review of Latest Evidence.
AB  - Periprocedural anticoagulation bridging is recommended to reduce the risk of
      thromboembolic events in patients at a higher risk of developing thromboembolism
      during the perioperative period. The optimal periprocedural anticoagulation
      strategy has not been established. Unfractionated heparin and low molecular
      heparin are used in preventing thromboembolism in the special population. Novel
      oral anticoagulants that directly inhibit thrombin (dabigatran) or factor Xa
      (rivaroxaban, apixaban) are shown as effective anticoagulants in preventing
      thromboembolism (venous thromboembolism) in various medical conditions. They have
      the advantage of having a faster onset, shorter half-lives, easier monitoring,
      and predicable doses. But there are disadvantages to newer anticoagulants such as
      the unavailability of definitive reversal agents and lack of data in patients
      with renal insufficiency. We review the latest evidence on the effects of newer
      oral anticoagulants in preventing thromboembolism and its bleeding risks. 

PMID- 26214207
TI  - The diversity of platelet microparticles.
AB  - PURPOSE OF REVIEW: Platelet microparticles are small extracellular vesicles
      abundant in blood. The present review will introduce the mechanisms underlying
      the generation of microparticles, and will describe the diverse microparticle
      subtypes identified to date. The most appropriate methodologies used to
      distinguish microparticle subtypes will be also presented. RECENT FINDINGS: Both
      the megakaryocytes and platelets can generate microparticles. Circulating
      microparticles originating from megakaryocytes are distinguished from those
      derived from activated platelets by the presence of CD62P, LAMP-1, and
      immunoreceptor-based activation motif receptors. Close examination of platelet
      activation has shed light on a novel mechanism leading to microparticle
      production. Under physiologic flow, microparticles bud off from long membrane
      strands formed by activated platelets. Furthermore, mounting evidence supports
      the notion of microparticle heterogeneity. Platelet microparticles are commonly
      characterized by the expression of surface platelet antigens and
      phosphatidylserine. In fact, only a fraction of platelet microparticles harbor
      phosphatidylserine, and a distinct subset contains respiratory-competent
      mitochondria. During disease, the microparticle surface may undergo
      posttranslational modifications such as citrullination, further supporting the
      concept of microparticle diversity. SUMMARY: An appreciation of the microparticle
      heterogeneity will support their development as potential biomarkers and may
      reveal functions unique to each microparticle subtype in health and disease.

PMID- 26214208
TI  - The roles of central amygdala D1 and D2 receptors on attentional performance in a
      five-choice task.
AB  - The central amygdala (CeA) has been shown to play an important role in mediating
      several attentional processes, including selective and sustained attention.
      Emerging evidence suggests that the connections between the CeA and the midbrain
      dopamine areas are important for attentional processing. However, little is known
      about the role of dopaminergic input into the CeA in mediating attentional
      processes. To investigate how dopamine activity in the CeA modulates attentional
      processing, CeA D1 and D2 receptors were temporarily inactivated during testing
      in a 5-choice task. In this task, rats were trained to detect 1 of 5 recessed
      ports that briefly illuminated in order to receive a food reward, therefore
      requiring the rats to successfully sustain their attention to monitor all 5 ports
      and selectively attend to the lit port. Then, rats were tested in several altered
      versions of the task to increase attentional load (e.g., variable ready period).
      In 2 experiments, the D1 antagonist CH 23390 or the D2 antagonist raclopride were
      infused into the bilateral CeA preceding the test sessions. D1, but not D2,
      inactivation reduced performance in the more demanding versions of the 5-choice
      task. Therefore, CeA D1 receptors might mediate attentional functions important
      for visual cue detection in a 5-choice task.

PMID- 26214210
TI  - Developmental exposure to methimazole increases anxiety behavior in zebrafish.
AB  - The role of thyroid hormones in vertebrate development has been well documented
      for several decades. As hypothyroidism during critical periods of development can
      cause defects to the development of every major organ system, including brain,
      eye, and general morphology, we hypothesized that hypothyroidism would affect
      specific behaviors. To assess this, we treated zebrafish with the hypothyroid
      drug methimazole (MMI) and examined changes in anxiety, shoaling, vision, and
      locomotion. Following low-dose MMI exposure for the first 10 days of life, a time
      of rapid and significant development, larvae were removed from treatment and
      allowed to develop until 1 month of age. Comparisons between treated and controls
      took place between 10 and 30 days postfertilization to examine times both during
      and after treatment. Using the novel tank and startle response tests, we found
      that anxiety behaviors are significantly increased following MMI treatment. These
      effects persisted for several days following removal from treatment and indicate
      a prolonged effect of early hypothyroidism. However, permanent MMI effects on
      anxiety were not observed, as anxiety behaviors of early treated zebrafish
      recovered to control levels following 10 days out of treatment. In contrast to
      the strong link between MMI treatment and anxiety, shoaling and visual behaviors
      were not significantly affected within our experimental parameters. This
      indicates that disruption of thyroid system functioning early in life can
      differentially affect behavior by specifically altering anxiety responses without
      producing indiscriminate changes to overall behavioral development.

PMID- 26214211
TI  - Correction to Ward et al. (2015).
AB  - Reports an error in "The impact of motivation on cognitive performance in an
      animal model of the negative and cognitive symptoms of schizophrenia" by Ryan D.
      Ward, Vanessa Winiger, Kerin K. Higa, Julia B. Kahn, Eric R. Kandel, Peter D.
      Balsam and Eleanor H. Simpson (Behavioral Neuroscience, 2015[Jun], Vol 129[3],
      292-299). There is a text error in the 4th paragraph of the Discussion section.
      The explanation for the abbreviation OFC was incorrectly listed as
      occipitofrontal circumference. It should have been orbitofrontal cortex. (The
      following abstract of the original article appeared in record 2015-18639-001.)
      Interactions between motivation and cognition are implicated in producing
      functional impairments and poor quality of life in psychiatric patients. This
      interaction, however, is not well understood at either the behavioral or neural
      level. We developed a procedure for mice in which a cognitive measure, sustained
      attention, is modulated by a motivationally relevant signal that predicts reward
      probability on a trial-by-trial basis. Using this paradigm, we tested the
      interaction between motivation and cognition in mice that model the increased
      striatal D2 receptor activity observed in schizophrenia patients (D2R-OE mice).
      In control mice, attention was modulated by signaled-reward probability. In D2R
      OE mice, however, attention was not modulated by reward-related cues. This
      impairment was not due to any global deficits in attention or maintenance of the
      trial-specific information in working memory. Turning off the transgene in D2R-OE
      mice rescued the motivational modulation of attention. These results indicate
      that deficits in motivation impair the ability to use reward-related cues to
      recruit attention and that improving motivation improves functional cognitive
      performance. These results further suggest that addressing motivational
      impairments in patients is critical to achieving substantive cognitive and
      functional gains.

PMID- 26214209
TI  - Long-term behavioral effects in a rat model of prolonged postnatal morphine
      exposure.
AB  - Prolonged morphine treatment in neonatal pediatric populations is associated with
      a high incidence of opioid tolerance and dependence. Despite the clinical
      relevance of this problem, our knowledge of long-term consequences is sparse. The
      main objective of this study was to investigate whether prolonged morphine
      administration in a neonatal rat is associated with long-term behavioral changes
      in adulthood. Newborn animals received either morphine (10 mg/kg) or equal volume
      of saline subcutaneously twice daily for the first 2 weeks of life. Morphine
      treated animals underwent 10 days of morphine weaning to reduce the potential for
      observable physical signs of withdrawal. Animals were subjected to nonstressful
      testing (locomotor activity recording and a novel-object recognition test) at a
      young age (Postnatal Days [PDs] 27-31) or later in adulthood (PDs 55-56), as well
      as stressful testing (calibrated forceps test, hot plate test, and forced swim
      test) only in adulthood. Analysis revealed that prolonged neonatal morphine
      exposure resulted in decreased thermal but not mechanical threshold. Importantly,
      no differences were found for total locomotor activity (proxy of drug
      reward/reinforcement behavior), individual forced swim test behaviors (proxy of
      affective processing), or novel-object recognition test. Performance on the novel
      object recognition test was compromised in the morphine-treated group at the
      young age, but the effect disappeared in adulthood. These novel results provide
      insight into the long-term consequences of opioid treatment during an early
      developmental period and suggest long-term neuroplastic differences in sensory
      processing related to thermal stimuli.

PMID- 26214212
TI  - Greater avoidance of a heroin-paired taste cue is associated with greater
      escalation of heroin self-administration in rats.
AB  - Heroin addiction is a disease of chronic relapse affecting over half of its
      users. Therefore, modeling individual differences in addiction-like behavior is
      needed to better reflect the human condition. In a rodent model, avoidance of a
      cocaine-paired saccharin cue is associated with greater cocaine seeking and
      taking. Here, we tested whether rats would avoid a saccharin cue when paired with
      the opportunity to self-administer heroin and whether the rats that most greatly
      avoid the heroin-paired taste cue would exhibit the greatest drug escalation over
      time, the greatest willingness to work for drug, and the greatest heroin-induced
      relapse. Adult male Sprague-Dawley rats received 5 min access to a 0.15%
      saccharin solution followed by the opportunity to self-administer either saline
      or heroin for 3 hr (short access) or 6 hr (extended access). Following 16 to 18
      pairings, terminal saccharin intake was used to categorize the rats into small
      (>200 licks/5min) or large (<200 licks/5min) suppressors and responding for drug
      was examined accordingly. Only 5% of the short access rats reached the criteria
      for large suppressors. This large suppressor did not differ from the small
      suppressors in drug-taking behavior. On the other hand, 50% of the extended
      access saccharin-heroin rats were large suppressors and showed the largest
      escalation of drug intake, drug-loading behavior, and the greatest relapse-like
      behaviors. Extended access small suppressors displayed drug-taking behaviors that
      were similar to rats in the short access heroin condition. Avoidance of a heroin
      paired taste cue reliably identifies individual differences in addiction-like
      behavior for heroin using extended drug access.

PMID- 26214213
TI  - Oxytocin reduces amygdala activity, increases social interactions, and reduces
      anxiety-like behavior irrespective of NMDAR antagonism.
AB  - Standard dopamine therapies for schizophrenia are not efficacious for negative
      symptoms of the disease, including asociality. This reduced social behavior may
      be due to glutamatergic dysfunction within the amygdala, leading to increased
      fear and social anxiety. Several studies have demonstrated the prosocial effects
      of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect
      of subchronic oxytocin on EEG activity in amygdala of mice during performance of
      the three-chamber social choice and open field tests following acute ketamine as
      a model of glutamatergic dysfunction. Oxytocin did not restore social deficits
      introduced by ketamine but did significantly increase sociality in comparison to
      the control group. Ketamine had no effect on time spent in the center during the
      open field trials, whereas oxytocin increased overall center time across all
      groups, suggesting a reduction in anxiety. Amygdala activity was consistent
      across all drug groups during social and nonsocial behavioral trials. However,
      oxytocin reduced overall amygdala EEG power during the two behavioral tasks.
      Alternatively, ketamine did not significantly affect EEG power throughout the
      tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related
      to both reduced anxiety and increased social behaviors. Data suggest that
      separate prosocial and social anxiety pathways may mediate social preference.

PMID- 26214214
TI  - Correction to Smith et al. (2013).
AB  - Reports an error in "Noradrenergic alpha-2 receptor modulators in the ventral bed
      nucleus of the stria terminalis: Effects on anxiety behavior in postpartum and
      virgin female rats" by Carl D. Smith, Christopher C. Piasecki, Marcus Weera,
      Joshua Olszewicz and Joseph S. Lonstein (Behavioral Neuroscience, 2013[Aug], Vol
      127[4], 582-597). Table 2 should have used the ratio of 5HIAA/serotonin - rather
      than the inverse - as the indicator of serotonin turnover. Using the correct
      ratio, differences in serotonin turnover between the postpartum and virgin
      females are: BSTv - 1.11 0.06 vs 0.79 0.11 (t 2.57, p 0.05); BSTd - 1.01 0.07 vs
      0.68 0.11 (t 2.58, p 0.05). That is, contrary to what was originally reported,
      postpartum females had higher serotonin turnover in both subregions of the BST
      compared to virgins. The penultimate sentence in the abstract noting serotonin
      turnover in mothers has been corrected in the online version of this article.
      (The following abstract of the original article appeared in record 2013-22430
      001.) Emotional hyperreactivity can inhibit maternal responsiveness in female
      rats and other animals. Maternal behavior in postpartum rats is disrupted by
      increasing norepinephrine release in the ventral bed nucleus of the stria
      terminalis (BSTv) with the alpha2-autoreceptor antagonist, yohimbine, or the more
      selective alpha2-autoreceptor antagonist, idazoxan (Smith et al., 2012). Because
      high noradrenergic activity in the BSTv can also increase anxiety-related
      behaviors, increased anxiety may underlie the disrupted mothering of dams given
      yohimbine or idazoxan. To assess this possibility, anxiety-related behaviors in
      an elevated plus maze were assessed in postpartum rats after administration of
      yohimbine or idazoxan. It was further assessed if the alpha2-autoreceptor agonist
      clonidine (which decreases norepinephrine release) would, conversely, reduce
      dams' anxiety. Groups of diestrous virgins were also examined. It was found that
      peripheral or intra-BSTv yohimbine did increase anxiety-related behavior in
      postpartum females. However, BSTv infusion of idazoxan did not reproduce
      yohimbine's anxiogenic effects and anxiety was not reduced by peripheral or intra
      BSTv clonidine. Because yohimbine is a weak 5HT1A receptor agonist, other groups
      of females received BSTv infusion of the 5HT1A receptor agonist 8OH-DPAT, but it
      did not alter their anxiety-related behavior. Lastly, levels of norepinephrine
      and serotonin in tissue punches from the BSTv did not differ between postpartum
      and diestrous rats, but serotonin turnover was higher in mothers. These results
      suggest that the impaired maternal behavior after BSTv infusion of yohimbine or
      idazoxan cannot both be readily explained by an increase in dams' anxiety, and
      that BSTv alpha2-autoreceptor modulation alone has little influence on anxiety
      related behaviors in postpartum or diestrous rats.

PMID- 26214215
TI  - Hippocampal acetylcholine depletion has no effect on anxiety, spatial novelty
      preference, or differential reward for low rates of responding (DRL) performance
      in rats.
AB  - We investigated the role of the septo-hippocampal cholinergic projection in
      anxiety, spatial novelty preference, and differential reward for low rates of
      responding (DRL) performance. Cholinergic neurons of the rat medial septum (MS)
      and the vertical limb of the diagonal band of Broca (VDB) were lesioned using the
      selective immunotoxin, 192 IgG-saporin. Rats were then tested on several
      behavioral tests previously shown to be sensitive to either (a) hippocampal
      lesions or (b) nonselective MS/VDB lesions which target both cholinergic and
      gamma-aminobutyric acid (GABA)-ergic projections, or both. Saporin lesions
      substantially reduced hippocampal cholinergic innervation, resulting in an
      absence of acetyl cholinesterase staining and markedly reduced choline
      acetyltransferase activity (mean reduction: 80 +/- 5%; range: 50-97%). However,
      the saporin-lesioned rats did not differ from control rats in any of the
      behavioral tests. Thus we found no evidence from these lesion studies that the
      septo-hippocampal cholinergic projection plays an essential role in anxiety,
      spatial novelty preference, or DRL.

PMID- 26214217
TI  - Hippocampectomy disrupts trace eye-blink conditioning in rabbits.
AB  - The role of the hippocampus (HFC) in trace eye-blink conditioning was evaluated
      using a 100-ms tone conditioned stimulus (CS), a 300- or 500-ms trace interval,
      and a 150-ms air puff unconditioned stimulus (UCS). Rabbits received complete
      hippocampectomy (dorsal & ventral), sham lesions, or neocortical lesions.
      Hippocampectomy produced differential effects in relation to the trace interval
      used. With a 300-ms trace interval, HPC-lesioned Ss showed profound resistance to
      extinction after acquisition. With a 500-ms trace interval, HPC-lesioned Ss did
      not learn the task (only 22% conditioned responses (CRs) after 25 sessions,
      whereas controls showed >80% after 10 sessions), and on the few trials in which a
      CR occurred, most were "nonadaptive" short-latency CRs (i.e., they started during
      or just after the CS and always terminated prior to UCS onset). The authors
      conclude that the HPC encodes a temporal relationship between CS and UCS, and
      when the trace interval is long enough (e.g., 500 ms), that the HPC is necessary
      for associative learning of the conditioned eye-blink response.

PMID- 26214216
TI  - The impact of hippocampal lesions on trace-eyeblink conditioning and forebrain
      cerebellar interactions.
AB  - Behavioral Neuroscience published a pivotal paper by Moyer, Deyo, and Disterhoft
      (1990) 25 years ago that described the impaired acquisition of trace-eyeblink
      conditioning in rabbits with complete removal of the hippocampus. As part of the
      Behavioral Neuroscience celebration commemorating the 30th anniversary of the
      journal, we reflect upon the impact of that study on understanding the role of
      the hippocampus, forebrain, and forebrain-cerebellar interactions that mediate
      acquisition and retention of trace-conditioned responses, and of declarative
      memory more globally. We discuss the expansion of the conditioning paradigm to
      species other than the rabbit, the heterogeneity of responses among hippocampal
      neurons during trace conditioning, the responsivity of hippocampal neurons
      following consolidation of conditioning, the role of awareness in conditioning,
      how blink conditioning can be used as a translational tool by assaying potential
      therapeutics for cognitive enhancement, how trace and delay classical
      conditioning may be used to investigate neurological disorders including
      Alzheimer's disease and schizophrenia, and how the 2 paradigms may be used to
      understand the relationship between declarative (explicit) and nondeclarative
      (implicit) memory systems.

PMID- 26214218
TI  - Using the spatial learning index to evaluate performance on the water maze.
AB  - The Morris water maze was developed in 1981 and quickly became the standard task
      for assessing spatial memory and spatial navigation. Twenty years ago, Gallagher,
      Burwell, and Burchinal (1993) reported new variables and measures, including a
      spatial learning index, that greatly enhanced the utility of the Morris water
      maze for assessing subtle differences in performance on the task. The learning
      index provided a single number that could be used to elucidate neurobiological
      measures of hippocampal dysfunction, for example, correlation of learning
      performance with a biomarker of aging. In this review, as part of the
      commemoration of the 30th anniversary of Behavioral Neuroscience, we describe how
      the spatial learning index has contributed to the field of learning and memory,
      how it has advanced our understanding of normal and pathological cognitive aging,
      and how it has contributed to translation of findings into other species.
      Finally, we provide instruction into how the learning index can be extended to
      other tasks and data sets.

PMID- 26214219
TI  - Severity of spatial learning impairment in aging: Development of a learning index
      for performance in the Morris water maze.
AB  - The Morris water maze task was originally designed to assess the rat's ability to
      learn to navigate to a specific location in a relatively large spatial
      environment. This article describes new measures that provide information about
      the spatial distribution of the rat's search during both training and probe trial
      performance. The basic new measure optimizes the use of computer tracking to
      identify the rat's position with respect to the target location. This proximity
      measure was found to be highly sensitive to age-related impairment in an
      assessment of young and aged male Long-Evans rats. Also described is the
      development of a learning index that provides a continuous, graded measure of the
      severity of age-related impairment in the task. An index of this type should be
      useful in correlational analyses with other neurobiological or behavioral
      measures for the study of individual differences in functional/biological decline
      in aging.

PMID- 26214220
TI  - LAT gel for laceration repair in the emergency department: not only for children?
AB  - OBJECTIVE: LAT (lidocaine, adrenaline, and tetracaine) gel is a topical
      anesthetic that can be applied on lacerations before suturing. It is considered
      easy to use and less painful than infiltrative anesthesia. Its use in laceration
      management has been studied the most in younger children.We aimed to describe the
      potential value of the use of LAT gel in older children and adults with simple
      lacerations. MATERIALS AND METHODS: As part of a quality audit project, we
      reviewed all emergency department records of patients who had LAT gel applied for
      laceration repair in a 3-month period following the initial protocol
      implementation. Patients younger than 8 years of age, under the influence of
      alcohol or drugs, or those who received additional sedation were excluded. The
      need for additional anesthesia after needle probing was used as the primary
      endpoint. RESULTS: Of the 89 patients included, 21 (23.6%) needed additional
      anesthesia. The length of the wound was significantly longer in the group who
      needed additional anesthesia (difference between medians 1 cm; 95% confidence
      interval 0.5-2; P<0.005). Lacerations located on the
      extremities/trunk/fingers/toes needed significantly more additional anesthesia
      compared with lacerations located on the head (19.1% difference between
      proportions; 95% confidence interval 1-34.8%; P<0.05). CONCLUSION: LAT gel is a
      valuable alternative to infiltrative anesthesia for laceration repair. Its use
      should not be limited to children. The application of LAT gel seems to be
      specifically suitable for short lacerations (<4 cm), lacerations located on the
      head, and simple finger lacerations.

PMID- 26214221
TI  - Tri-icosahedral Gold Nanocluster [Au37(PPh3)10(SC2H4Ph)10X2](+): Linear Assembly
      of Icosahedral Building Blocks.
AB  - The [Au37(PPh3)10(SR)10X2](+) nanocluster (where SR = thiolate and X = Cl/Br) was
      theoretically predicted in 2007, but since then, there has been no experimental
      success in the synthesis and structure determination. Herein, we report a
      kinetically controlled, selective synthesis of [Au37(PPh3)10(SC2H4Ph)10X2](+)
      (counterion: Cl(-) or Br(-)) with its crystal structure characterized by X-ray
      crystallography. This nanocluster shows a rod-like structure assembled from three
      icosahedral Au13 units in a linear fashion, consistent with the earlier
      prediction. The optical absorption and the electrochemical and catalytic
      properties are investigated. The successful synthesis of this new nanocluster
      allows us to gain insight into the size, structure, and property evolution of
      gold nanoclusters that are based upon the assembly of icosahedral units (i.e.,
      cluster of clusters). Some interesting trends are identified in the evolution
      from the monoicosahedral [Au13(PPh3)10X2](3+) to the bi-icosahedral
      [Au25(PPh3)10(SC2H4Ph)5X2](2+) and to the tri-icosahedral
      [Au37(PPh3)10(SC2H4Ph)10X2](+) nanocluster, which also points to the possibility
      of achieving even longer rod nanoclusters based upon assembly of icosahedral
      building blocks. 

PMID- 26214222
TI  - Testicular yolk sac tumor and impaired spermatogenesis in a Holstein Friesian
      calf.
AB  - Yolk sac tumors are testicular germ-cell tumors of the non-seminoma type. In
      cattle, this neoplasm is very rare and to date has only been described three
      times. In human males, it usually occurs in infants and children.
      Immunohistochemistry provides solid criteria for diagnostics. Especially present
      pathognomonic Schiller-Duval bodies are helpful for identification. In this
      report, a 32-day-old Holstein Friesian calf presented with a highly enlarged
      right testis. Sonographic examination was performed and blood samples were taken
      to measure testosterone and estrogen levels. Furthermore, the testis was
      surgically removed and macroscopically, histologically, and immunohistochemically
      examined which lead to the diagnosis of testicular yolk sac tumor. The second
      testis was descended until the age of nine months and histology revealed impaired
      spermatogenesis. This report provides the first sonographic images of bovine
      testicular yolk sac tumor as well as the first information about hormone levels
      in calves with this neoplasm. It also shows the importance to combine anamnesis,
      histomorphological, and immunohistochemical findings in order to diagnose yolk
      sac tumors when pathognomonic structures are not present. 

PMID- 26214223
TI  - Catalytic Asymmetric Cascade Vinylogous Mukaiyama 1,6-Michael/Michael Addition of
      2-Silyloxyfurans with Azoalkenes: Direct Approach to Fused Butyrolactones.
AB  - An unprecedented cascade vinylogous Mukaiyama 1,6-MA/MA of 2-silyloxyfurans and
      azoalkenes was realized with a Cu(II)/(t)Bu-Box complex. An array of fused
      butyrolactones containing multiple stereocenters was generally obtained in good
      yield (up to 90% yield) with exclusive diastereoselectivity (>20:1 dr) and
      excellent enantioselectivity (up to 99% ee). Carbon isotope effects measured by
      (13)C NMR revealed a stepwise mechanism for this annulation process. 

PMID- 26214224
TI  - Intracellular expression of an anti-idiotypic antibody single-chain variable
      fragment reduces porcine reproductive and respiratory syndrome virus infection in
      MARC-145 cells.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is the
      causative agent of porcine reproductive and respiratory syndrome; it is one of
      the most economically important viral diseases affecting the swine industry
      worldwide. At present, neither live-attenuated nor inactivated PRRSV vaccines can
      provide sustainable disease control. Our previous studies have demonstrated that
      PRRSV infection can produce the auto-anti-idiotypic antibodies (aAb2s) specific
      to the idiotypic antibodies against PRRSV GP5, which plays an important role in
      the host immune responses to PRRSV infection. In the present study, a single
      chain variable antibody fragment (scFv) from the monoclonal anti-idiotypic
      antibody specific for the idiotypic antibody against GP5 was expressed in MARC
      145 cells and its effect on virus infection in vitro was evaluated. METHODS: An
      scFv was constructed from the anti-idiotypic antibody (Mab2-5G2) and was named
      5G2scFv. The lentiviral vector system was used as a vehicle to deliver 5G2scFv
      into MARC-145 cells. The effect of 5G2scFv expression in MARC-145 was analysed by
      determining the PRRSV N protein level and the virus titre in the supernatant.
      Virus attachment and the level of type I interferon (IFN) were determined to
      elucidate the mechanism of the scFv effect. RESULTS: 5G2scFv was delivered in
      MARC-145 cells using the lentiviral vector system as confirmed by the western
      blot and indirect immunofluorescence assays. The PRRSV challenge experiments
      demonstrated that expressed 5G2scFv in MARC-145 strongly reduced PRRSV infection
      and replication by inhibiting protein synthesis and progeny virus production.
      This effect was not due to the change of viability or virus binding, but
      increased IFN-alpha at messenger RNA and protein levels. CONCLUSIONS: The
      expression of the anti-idiotypic antibody 5G2scFv in MARC-145 cells has the
      interferential effect on PRRSV infection in the cells by induction of IFN-alpha,
      which provides a novel therapeutic approach for PRRSV infection.

PMID- 26214225
TI  - "Now I know I can make a difference": Generativity and activity engagement as
      predictors of meaning making in adolescents and emerging adults.
AB  - This study examined generativity (concern for future generations as a legacy of
      the self) and activity engagement as predictors of meaning making in young
      people's personal accounts of their key activity experiences. We elicited stories
      regarding events within participants' "most engaging activity," self-reports on
      generativity, and behavioral participation and psychological engagement in
      activities in 2 separate samples: an emerging adult sample and an adolescent
      sample. The stories were coded for meaning making, defined as degree of insight
      into individuals' understanding of themselves or the world (McLean & Pratt,
      2006). Psychological engagement, but not behavioral participation, was positively
      associated with meaning making. Moreover, generativity was significantly and
      positively related to psychological engagement, and predicted meaning making,
      even after controlling for psychological engagement. Findings suggest that
      different types of activities can offer a potential context for fostering early
      generativity and meaning making, and that generativity in adolescence and
      emerging adulthood is related to the development of insight and meaning making.

PMID- 26214226
TI  - Antecedents and outcomes of level and rates of change in perceived control: The
      moderating role of age.
AB  - Perceived control is interrelated with aging-related outcomes across adulthood
      and old age. Relatively little is known, however, about resources as antecedents
      of longitudinal change in perceived control and the role of perceived control as
      a buffer against mortality risk when these resources are low. We examined
      functional limitations, depressive symptoms, and emotional support as antecedents
      of level and rates of change in perceived control and whether level and rates of
      change in perceived control buffer the relations between high functional
      limitations and depressive symptoms and lack of emotional support and mortality
      risk. In addition, age was investigated as a moderator of these associations. To
      do so, we used 16-year longitudinal data from participants in the Americans'
      Changing Lives (ACL) Study who were at least 40 years old at Wave 1 (N = 2,540;
      mean age = 62.85, SD = 12.15; 65% women). With respect to the antecedents of
      perceived control, results indicated that more functional limitations and
      depressive symptoms, as well as having less emotional support, were each
      associated with lower levels of and stronger declines in perceived control over
      time. Additionally, more functional limitations and less emotional support were
      more detrimental to levels of perceived control in midlife compared to old age.
      Focusing on outcomes of perceived control, more positive rates of change in
      perceived control protected against mortality risk for those with fewer
      functional limitations and depressive symptoms and more emotional support, and
      this was more pronounced for functional limitations and depressive symptoms in
      old age as compared to midlife. Our discussion focuses on the complex interplay
      among perceived control, functional limitations, depressive symptoms, and
      emotional support; how they vary with age; and the implications of our findings
      for interventions.

PMID- 26214227
TI  - The development of leisure boredom in early adolescence: Predictors and
      longitudinal associations with delinquency and depression.
AB  - The literature proposes that leisure boredom may systematically increase during
      adolescence. Moreover, some authors assume that this hypothesized developmental
      trend is associated with increases in youthful delinquency and depression.
      Individual dispositions (e.g., temperamental disinhibition) are believed to
      exacerbate the relationship between boredom and delinquency. This study
      investigated whether (1) leisure boredom really is an increasing phenomenon
      during early adolescence; (2) gender, temperamental disinhibition, shyness,
      family relationship quality, peer rejection, a deprived school context, and
      rural/urban living explain developmental variations in boredom; (3) boredom is
      longitudinally and reciprocally related to delinquency and depression; and (4)
      bored disinhibited adolescents are particularly likely to become delinquent and
      to use delinquent acts to mitigate boredom. Analyses were based on a German
      sample of school students (N = 722) who provided annual self-reports on study
      variables from age 10 to 14 years. Bivariate growth curve models captured
      correlations between developmental trajectories of boredom and
      delinquency/depression. Cross-lagged models examined reciprocal short-term
      associations. Analyses revealed a modest increase in leisure boredom during early
      adolescence. Disinhibition and qualities of proximal social contexts (family,
      peers, school) were related to boredom with peer rejection showing the most
      consistent longitudinal association. Boredom was developmentally associated with
      depression whereas longitudinal associations with delinquency were weaker and
      more short-term. Temperamentally disinhibited adolescents appeared to buffer
      leisure boredom by means of delinquency. Results support person-context models of
      leisure boredom with regard to its etiology and consequences. Findings further
      demonstrate that leisure boredom plays a prominent role in the developmental
      adaptation of adolescents.

PMID- 26214228
TI  - Developmental investigation of the domain-specific nature of the life
      satisfaction construct across the post-school transition.
AB  - This study evaluated the nature of the life satisfaction construct with an
      emphasis on the comparison between a global or domain-specific operationalization
      during the transition from adolescence to adulthood. A combination of person
      centered and variable-centered methods were used to analyze 7 waves of data
      covering the postschool transition from a sample of 24,721 youth participating in
      Longitudinal Study of Australian Youth (LSAY) between 1998 and 2010. Evidence for
      the increasing importance of a domain-specific approach as adolescents entered
      adulthood was provided by: (1) factor analyses identifying a 3-factor model
      covering achievement, family, and leisure satisfaction that proved invariant
      across time waves; (2) factor mixture analyses showing shape-related differences
      between profiles (i.e., within-profile differences between domains) that
      increased as young people moved into adulthood.

PMID- 26214229
TI  - Effects of learning with gesture on children's understanding of a new language
      concept.
AB  - Asking children to gesture while being taught a concept facilitates their
      learning. Here, we investigated whether children benefitted equally from
      producing gestures that reflected speech (speech-gesture matches) versus gestures
      that complemented speech (speech-gesture mismatches), when learning the concept
      of palindromes. As in previous studies, we compared the utility of each gesture
      strategy to a speech alone strategy. Because our task was heavily based on
      language ability, we also considered children's phonological competency as a
      predictor of success at posttest. Across conditions, children who had low
      phonological competence were equally likely to perform well at posttest. However,
      gesture use was predictive of learning for children with high phonological
      competence: Those who produced either gesture strategy during training were more
      likely to learn than children who used a speech alone strategy. These results
      suggest that educators should be encouraged to use either speech-gesture match or
      mismatch strategies to aid learners, but that gesture may be especially
      beneficial to children who possess basic skills related to the new concept, in
      this case, phonological competency. Results also suggest that there are
      differences between the cognitive effects of naturally produced speech-gesture
      matches and mismatches, and those that are scripted and taught to children.

PMID- 26214230
TI  - Educational, employment, and social participation of young adult graduates from
      the paediatric Southern Cochlear Implant Programme, New Zealand.
AB  - OBJECTIVES: The purpose of this study is to observe the education and vocational
      achievements and social participation of cochlear implant recipients as they
      graduate from a paediatric cochlear implant programme and identify any
      significant associations that might exist. METHOD: This study identified 56
      patients from the Southern Cochlear Implant Programme (SCIP) who received
      cochlear implants before the age of 19 (paediatric) and are now over the age of
      19 (adult). A questionnaire investigated their education, employment, and
      identity with the hearing and deaf communities. Also included were the
      satisfaction with life scale and Hearing Participation Scale (HPS). Subjects
      ranged in age from 19 to 32. RESULTS: Twenty-six patients responded to the
      questionnaire, including one non-user. Twenty identified strongly or very
      strongly with the hearing community. There was weak evidence of a linear
      association between strong identity with the hearing community and a higher HPS
      score. No other statistically significant associations were detected.
      Interestingly, 12 out of 26 participants found employment through family.
      CONCLUSION: Positive outcome trends in education and employment were seen in this
      study although no statistical significance was achieved. There is a strong bias
      for those who use their cochlear implants regularly, and there are no data
      available for those who do not use their cochlear implants for comparison as only
      one non-user completed the survey, despite efforts to include this group. This
      study shows that there is perceived benefit in implantation for patients who use
      it regularly but further research is needed with a more diverse group of cochlear
      implant recipients.

PMID- 26214231
TI  - Effectiveness and clinical response rates of a residential eating disorders
      facility.
AB  - The purpose of this study was to determine the effectiveness of a residential
      treatment program for adults and adolescents with eating disorders across a wide
      spectrum of measures. Data on body mass, eating disorder severity, depression,
      anxiety, and two measures of quality of life were collected on 139 consecutively
      admitted adolescents and 111 adults at a residential treatment program (N = 250).
      The same measures were completed at post-treatment. Group level analyses showed
      that adults and adolescents improved on all measures analyzed. Only 1.7% of
      adolescents and 2.3% of adults were below a Body Mass Index of 18.5 at discharge.
      Positive results across diagnoses and ages are reported for three subscales of
      the Eating Disorder Inventory-3, with clinical response rates reported. Using
      clinical responder analyses, it was found that for all individuals struggling
      with secondary issues, 74.7% were responders on the Beck Depression Inventory-II,
      41.0% on the Beck Anxiety Inventory, 63.5% on a measure of quality of life, and
      95.8% were responders on the physical subscale and 72.6% on the mental subscale
      of the SF-36-v2. This study suggests that residential treatment for eating
      disorders is effective at the group level, and it was effective for the majority
      of individuals within the group. 

PMID- 26214232
TI  - Shift Work and Prostate Cancer Incidence in Industrial Workers: A Historical
      Cohort Study in a German Chemical Company.
AB  - BACKGROUND: There is inconsistent evidence for a possible carcinogenic effect of
      shift work. In particular, little is known about the putative association of
      shift work with prostate cancer. METHOD: We studied a cohort of 27,828 male
      industrial production workers residing in the German federal state of Rhineland
      Palatinate who worked for at least one year in a chemical company in the period
      1995-2005. We obtained data on shift work and potential confounders including
      age, occupational task, and duration of employment from personnel files and from
      the records of the occupational health service. New cases of cancer in the period
      2000-2009 were ascertained from the state cancer registry. Differences in risk
      between shift workers and daytime workers were analyzed with Cox regression,
      stratified by stage of cancer, and adjusted for potential confounding effects.
      RESULTS: There were 146 new cases of prostate cancer in 12,609 rotating shift
      workers and 191 in 15,219 daytime workers. The median year of birth was 1960 in
      the first group and 1959 in the second. The shift workers did not have an
      elevated hazard ratio for prostate cancer in comparison to the daytime workers
      (HR = 0.93, 95% confidence interval [CI] 0.73-1.18). Some differences were seen
      depending on tumor stage. Both groups of workers had a higher incidence of
      prostate carcinoma than the general population (standardized incidence rate [SIR]
      = 1.44, 95% CI 1.22-1.70 for daytime workers; SIR = 1.51, 95% CI 1.30-1.74 for
      shift workers). CONCLUSION: In this well-documented, large-scale cohort study,
      the incidence of prostate cancer among shift workers did not differ from that
      among daytime workers. In the authors' opinion, further follow-up of this
      relatively young cohort is required.

PMID- 26214233
TI  - Evaluating Guidelines: A Review of Key Quality Criteria.
AB  - BACKGROUND: Guidelines of high methodological quality make an essential
      contribution to the quality assurance of medical knowledge. The detailed
      evaluation of guideline quality is a complex and time-consuming task. The answers
      to a few key questions generally suffice for an initial, rapid assessment of the
      quality and utility of a guideline. METHOD: We selectively searched the pertinent
      literature for guideline-assessing instruments and analyzed selected ones with
      respect to their target group, purpose, orientation, and comprehensiveness. We
      identified key questions from brief instruments that can be used to assess
      guideline quality rapidly. RESULTS: A comparison of ten instruments revealed that
      most were designed to provide a highly detailed assessment of guideline quality.
      Four recently developed instruments enable a rough and rapid assessment. They
      focus, in essence, on four key questions: Was the evidence analyzed
      systematically? Does the evidence support the recommendations? Is the goal of the
      guideline formulated, and are the authors named? Is the organization of the
      guideline easy to follow, and are the recommendations clearly signposted?
      CONCLUSION: Alongside the comprehensive instruments for assessing guidelines,
      such as DELBI and AGREE II, rapid-assessment instruments are a convenient tool
      for gaining a quick impression of the value of a guideline.

PMID- 26214234
TI  - The Diagnosis and Treatment of Bronchopulmonary Carcinoid.
AB  - BACKGROUND: The spectrum of primary neuroendocrine tumors of the lungs ranges
      from typical carcinoid tumors, which are relatively benign, to highly aggressive
      small-cell carcinoma. In this review, we summarize the treatment of
      bronchopulmonary carcinoid, a disease with an incidence of 0.5 per 100,000
      persons per year in Western countries. METHOD: We selectively searched the PubMed
      database for scientific evidence on the treatment of bronchopulmonary carcinoid,
      considering only articles published up to February 2015. We also performed a
      survival analysis of 84 patients with this disease who underwent
      interdisciplinary treatment at the University of Freiburg Medical Center.
      RESULTS: Carcinoid tumors account for less than 1% of all lung tumors. They
      manifest themselves clinically with cough (35%), hemoptysis (25%), and/or
      bronchial obstruction (40%), depending on their location, size, and pattern of
      growth. 30% of patients are asymptomatic, and less than 1% have hormone
      associated symptoms. Typical and atypical carcinoid tumors are distinguished on a
      histological basis; the histologic differential diagnosis also includes large
      cell neuroendocrine tumors and small-cell carcinoma of the lung. 80% of patients
      who undergo resection of typical carcinoid tumors survive at least 10 years.
      Atypical carcinoid tumors recur more commonly than typical ones. If the
      mediastinal lymph nodes are involved, adjuvant treatment should be considered.
      CONCLUSION: Because of their rarity, the treatment of bronchopulmonary carcinoid
      tumors presents an interdisciplinary challenge. Surgical resection, the treatment
      of choice for local carcinoid tumors, generally leads to long-term survival. The
      existing registers should be made more comprehensive so that the treatment of
      this disease can be better in the future.

PMID- 26214235
TI  - Duration of Immobilization to Be Factored in.

PMID- 26214236
TI  - Age Should Be no Obstacle to Treatment.

PMID- 26214237
TI  - Take Courage to Perform Open Articular Surface Repair.

PMID- 26214238
TI  - In Reply.

PMID- 26214239
TI  - Pterin-Dependent Mono-oxidation for the Microbial Synthesis of a Modified
      Monoterpene Indole Alkaloid.
AB  - Monoterpene indole alkaloids (MIAs) have important therapeutic value, including
      as anticancer and antimalarial agents. Because of their chemical complexity,
      therapeutic MIAs, or advanced intermediates thereof, are often isolated from the
      native plants. The microbial synthesis of MIAs would allow for the rapid and
      scalable production of complex MIAs and MIA analogues for therapeutic use. Here,
      we produce the modified MIA hydroxystrictosidine from glucose and the monoterpene
      secologanin via a pterin-dependent mono-oxidation strategy. Specifically, we
      engineered the yeast Saccharomyces cerevisiae for the high-level synthesis of
      tetrahydrobiopterin to mono-oxidize tryptophan to 5-hydroxytryptophan, which,
      after decarboxylation to serotonin, is coupled to exogenously fed secologanin to
      produce 10-hydroxystrictosidine in an eight-enzyme pathway. We selected
      hydroxystrictosidine as our synthetic target because hydroxylation at the 10'
      position of the alkaloid core strictosidine provides a chemical handle for the
      future chemical semisynthesis of therapeutics. We show the generality of the
      pterin-dependent mono-oxidation strategy for alkaloid synthesis by hydroxylating
      tyrosine to L-DOPA-a key intermediate in benzylisoquinoline alkaloid (BIA)
      biosynthesis-and, thereafter, further converting it to dopamine. Together, these
      results present the first microbial synthesis of a modified alkaloid, the first
      production of tetrahydrobiopterin in yeast, and the first use of a pterin
      dependent mono-oxidation strategy for the synthesis of L-DOPA. This work opens
      the door to the scalable production of MIAs as well as the production of modified
      MIAs to serve as late intermediates in the semisynthesis of known and novel
      therapeutics. Further, the microbial strains in this work can be used as plant
      pathway discovery tools to elucidate known MIA biosynthetic pathways or to
      identify pathways leading to novel MIAs. 

PMID- 26214240
TI  - Iodine-Catalyzed Direct Olefination of 2-Oxindoles and Alkenes via Cross
      Dehydrogenative Coupling (CDC) in Air.
AB  - A direct intermolecular olefination of sp(3) C-H bond between 2-oxindoles and
      simple alkenes via a Cross-Dehydrogenative Coupling (CDC) strategy has been
      developed. In the absence of additional base, moderate to excellent yields have
      been obtained by using a catalytic amount of iodine with atmospheric oxygen as
      the reoxidant. Based on the observation of a radical capture experiment, the
      transformation is proposed to proceed via a radical process. 

PMID- 26214241
TI  - Frustrated Lewis Pairs.
AB  - The articulation of the notion of "frustrated Lewis pairs" (FLPs), which emerged
      from the discovery that H2 can be reversibly activated by combinations of
      sterically encumbered Lewis acids and bases, has prompted a great deal of recent
      activity. Perhaps the most remarkable consequence has been the development of FLP
      catalysts for the hydrogenation of a range of organic substrates. In the past 9
      years, the substrate scope has evolved from bulky polar species to include a wide
      range of unsaturated organic molecules. In addition, effective stereoselective
      metal-free hydrogenation catalysts have begun to emerge. The mechanism of this
      activation of H2 has been explored, and the nature and range of Lewis acid/base
      combinations capable of effecting such activation have also expanded to include a
      variety of non-metal species. The reactivity of FLPs with a variety of other
      small molecules, including olefins, alkynes, and a range of element oxides, has
      also been developed. Although much of this latter chemistry has uncovered unique
      stoichiometric transformations, metal-free catalytic hydroamination, CO2
      reduction chemistry, and applications in polymerization have also been achieved.
      The concept is also beginning to find applications in bioinorganic and materials
      chemistry as well as heterogeneous catalysis. This Perspective highlights many of
      these developments and discusses the relationship between FLPs and established
      chemistry. Some of the directions and developments that are likely to emerge from
      FLP chemistry in the future are also presented. 

PMID- 26214242
TI  - Contusion Contrast Extravasation Depicted on Multidetector Computed Tomography
      Angiography Predicts Growth and Mortality in Traumatic Brain Contusion.
AB  - Traumatic brain injury (TBI) is the main cause of death in trauma victims and
      causes high rates of disability and neurological sequelae. Approximately 38-65%
      of traumatic brain contusions (TBC) demonstrate hemorrhagic expansion on serial
      computed tomography (CT) scans. Thus far, however, no single variable can
      accurately predict the hemorrhage expansion of a TBC. Our purpose was to evaluate
      contrast extravasation (CE) as a predictor of expansion, mortality, and poor
      outcome in TBC in a Brazilian cohort. After Institutional Review Board approval,
      we used multidetector CT angiography (MDCTA) to study 121 consecutive patients
      (106 men, 87.6%) with ages varying from 10 to 85 years. Informed consent was
      obtained from all subjects. The clinical and imaging findings were correlated
      with the findings on the initial MDCTA using either the Fisher exact test or
      Student t test and a multivariate logistic regression model. Of the persons who
      presented CE in TBC, 21.8% died (in-hospital mortality), whereas in the absence
      of this sign, the mortality rate was 7.6% (p = 0.014). In addition, expansion of
      the hemorrhagic component of the TBC was detected in 61.1% of the CE-positive
      patients, whereas expansion was only observed in 10% of the CE-negative patients
      (p < 0.001). Poor outcome was observed in 24.2% of the patients in the CE
      negative group, but in the presence of CE, 72.7% evolved with poor outcome (p <
      0.001). The CE was a strong independent predictor of expansion, poor outcome, and
      increased risk of in-hospital mortality in our series of patients with TBC.

PMID- 26214243
TI  - The association of cytokine genes polymorphisms and susceptibility to aplastic
      anemia in Egyptian patients.
AB  - BACKGROUND AND OBJECTIVE: Aplastic anemia (AA) remains a rare disease, with very
      interesting pathophysiology that is being investigated for years now. The present
      study aimed to determine the association between cytokine gene polymorphisms (TGF
      beta1 -509 C/T, TNF-alpha -308 G/A, IFN-gamma +874 A/T) and susceptibility to AA
      in Egyptian patients. METHODS: The study included 80 participants subjected to
      determination of gene polymorphisms on genomic DNA using polymerase chain
      reaction-restriction fragment length polymorphism assay. RESULTS: It was found
      that IFN-gamma +874 A/T gene polymorphism is associated with three-fold increased
      risk of development of AA (odds ratio (OR) 3.116, P = 0.019), while TNF-alpha 
      308 G/A gene polymorphism is associated with decreased risk (OR 0.318, P =
      0.026). TGF-beta1 -509 C/T gene polymorphism showed comparable risk between
      patients and controls (P = 0.263). CONCLUSION: IFN-gamma +874 A/T gene
      polymorphism is associated with the etiology of AA in Egyptian patients.

PMID- 26214244
TI  - Recent Trends in the Identification of Incidental Pulmonary Nodules.
AB  - RATIONALE: Pulmonary nodules are common incidental findings, but information
      about their incidence in the era of computed tomography (CT) is lacking.
      OBJECTIVES: To examine recent trends in pulmonary nodule identification. METHODS:
      We used electronic health records and natural language processing to identify
      members of an integrated health system who had nodules measuring 4 to 30 mm. We
      calculated rates of chest CT imaging, nodule identification, and receipt of a new
      lung cancer diagnosis within 2 years of nodule identification, and standardized
      rates by age and sex to estimate the frequency of nodule identification in the
      U.S. population in 2010. MEASUREMENTS AND MAIN RESULTS: Between 2006 and 2012,
      more than 200,000 adult members underwent 415,581 chest CT examinations. The
      annual frequency of chest CT imaging increased from 1.3 to 1.9% for all adult
      members, whereas the frequency of nodule identification increased from 24 to 31%
      for all scans performed. The annual rate of chest CT increased from 15.4 to 20.7
      per 1,000 person-years, and the rate of nodule identification increased from 3.9
      to 6.6 per 1,000 person-years, whereas the rate of a new lung cancer diagnosis
      remained stable. By extrapolation, more than 4.8 million Americans underwent at
      least one chest CT scan and 1.57 million had a nodule identified, including
      63,000 who received a new lung cancer diagnosis within 2 years. CONCLUSIONS:
      Incidental pulmonary nodules are an increasingly common consequence of routine
      medical care, with an incidence that is much greater than recognized previously.
      More frequent nodule identification has not been accompanied by increases in the
      diagnosis of cancerous nodules.

PMID- 26214245
TI  - Plasmonic Properties of Silicon Nanocrystals Doped with Boron and Phosphorus.
AB  - Degenerately doped silicon nanocrystals are appealing plasmonic materials due to
      silicon's low cost and low toxicity. While surface plasmonic resonances of boron
      doped and phosphorus-doped silicon nanocrystals were recently observed, there
      currently is poor understanding of the effect of surface conditions on their
      plasmonic behavior. Here, we demonstrate that phosphorus-doped silicon
      nanocrystals exhibit a plasmon resonance immediately after their synthesis but
      may lose their plasmonic response with oxidation. In contrast, boron-doped
      nanocrystals initially do not exhibit plasmonic response but become plasmonically
      active through postsynthesis oxidation or annealing. We interpret these results
      in terms of substitutional doping being the dominant doping mechanism for
      phosphorus-doped silicon nanocrystals, with oxidation-induced defects trapping
      free electrons. The behavior of boron-doped silicon nanocrystals is more
      consistent with a strong contribution of surface doping. Importantly, boron-doped
      silicon nanocrystals exhibit air-stable plasmonic behavior over periods of more
      than a year. 

PMID- 26214246
TI  - Microplicae--Specialized Surface Structure of Epithelial Cells of Wet-Surfaced
      Oral Mucosa.
AB  - The surface structure of the superficial cells of the oral mucosa is decorated
      with numerous membrane ridges, termed microplicae (MPLs). The MPL structure is
      typical of the epithelial surfaces that are covered with protective mucus. Cell
      membrane MPLs are no longer seen as passive consequences of cellular activity.
      The interaction between MPLs and the mucins has been demonstrated, however the
      role of MPL structure seen on the upper surface of the oral epithelial cells is
      speculative. The cell surface is of potentially great significance, as it harbors
      many markers for refined prognosis and targets for oral mucosal diseases and
      cancer therapy. With these aspects in mind, we conducted the present review of
      the MPL structure and function in order to form the basis for further studies of
      MPLs of the oral epithelial cells. 

PMID- 26214247
TI  - N-Cinnamoyltetraketide Derivatives from the Leaves of Toussaintia orientalis.
AB  - Seven N-cinnamoyltetraketides (1-7), including the new Z-toussaintine E (2),
      toussaintine F (6), and toussaintine G (7), were isolated from the methanol
      extract of the leaves of Toussaintia orientalis using column chromatography and
      HPLC. The configurations of E-toussaintine E (1) and toussaintines A (3) and D
      (5) are revised based on single-crystal X-ray diffraction data from racemic
      crystals. Both the crude methanol extract and the isolated constituents exhibit
      antimycobacterial activities (MIC 83.3-107.7 MUM) against the H37Rv strain of
      Mycobacterium tuberculosis. Compounds 1, 3, 4, and 5 are cytotoxic (ED50 15.3
      105.7 MUM) against the MDA-MB-231 triple negative aggressive breast cancer cell
      line. 

PMID- 26214248
TI  - Further developments in summarising and meta-analysing single-case data: An
      illustration with neurobehavioural interventions in acquired brain injury.
AB  - Data analysis for single-case designs is an issue that has prompted many
      researchers to propose a variety of alternatives, including use of randomisation
      tests, regression-based procedures, and standardised mean difference. Another
      option consists in computing unstandardised or raw differences between
      conditions: the changes in slope and in level, or the difference between the
      projected baseline (including trend) and the actual treatment phase measurements.
      Apart from the strengths of these procedures (potentially easier interpretation
      clinically, separate estimations and an overall quantification of effects,
      reasonable performance), they require further development, such as (a) creating
      extensions for dealing with methodologically strong designs such as multiple
      baseline, (b) achieving comparability across studies and making possible meta
      analytical integrations, and (c) implementing software for the extensions. The
      proposals are illustrated herein in the context of a meta-analysis of 28 studies
      on (neuro)behavioural interventions in adults who have challenging behaviours
      after acquired brain injury. 

PMID- 26214249
TI  - Evaluation of chemical constitute, fatty acids and antioxidant activity of the
      fruit and seed of sea buckthorn (Hippophae rhamnoides L.) grown wild in Iran.
AB  - In this investigation, the chemical compositions of berries from sea buckthorn
      were studied. The amount of ascorbic acid and beta-carotene determined by HPLC
      was 170 mg/100 g FW and 0.20 mg/g FW, respectively. Total phenols, anthocyanins,
      acidity and total soluble solids (TSS) contents were 247 mg GAE/100 g FW, 3 mg/L
      (cyanidin-3-glucoside), 5.32% and 13.8%, respectively. Fruit antioxidant activity
      determined by the ferric reducing ability of plasma (FRAP) method was 24.85 mM
      Fe/100 g FW. Results confirmed the presence of six dominant fatty acids
      (determined by GC) in fruit including linoleic (34.2%), palmitoleic (21.37%),
      palmitic (17.2%), oleic (12.8%), linolenic (5.37%) and stearic acid (1.67%). Five
      dominant fatty acids of the seeds were linoleic (42.36%), linolenic (21.27%),
      oleic (21.34%), palmitic (6.54%) and stearic acid (2.54%). The nitrogen content
      was 3.96%. The P, K, Ca, Mg, Fe, Zn, Mn, Cu, Cd and Cl contents of fruit were
      491, 1674, 1290, 990, 291, 29.77, 108.37, 17.87, 0.021 and 2.18 mg/kg DW,
      respectively.

PMID- 26214250
TI  - Distinguishing adjacent molecules on a surface using plasmon-enhanced Raman
      scattering.
AB  - Unambiguous chemical identification of individual molecules closely packed on a
      surface can offer the possibility to address single chemical species and monitor
      their behaviour at the individual level. Such a degree of spatial resolution can
      in principle be achieved by detecting their vibrational fingerprints using tip
      enhanced Raman scattering (TERS). The chemical specificity of TERS can be
      combined with the high spatial resolution of scanning probe microscopy
      techniques, an approach that has stimulated extensive research in the field.
      Recently, the development of nonlinear TERS in a scanning tunnelling microscope
      has pushed the spatial resolution down to ~0.5 nm, allowing the identification of
      the vibrational fingerprints of isolated molecules on Raman-silent metal
      surfaces. Although the nonlinear TERS component is likely to help sharpen the
      optical contrast of the acquired image, the TERS signal still contains a
      considerable contribution from the linear term, which is spatially less confined.
      Therefore, in the presence of different adjacent molecules, a mixing of Raman
      signals may result. Here, we show that using a nonlinear scanning tunnelling
      microscope-controlled TERS set-up, two different adjacent molecules that are
      within van der Waals contact and of very similar chemical structure (a metal
      centred porphyrin and a free-base porphyrin) on a silver surface can be
      distinguished in real space. In addition, with the help of density functional
      theory simulations, we are also able to determine their adsorption configurations
      and orientations on step edges and terraces. 

PMID- 26214251
TI  - Deterministic photon-emitter coupling in chiral photonic circuits.
AB  - Engineering photon emission and scattering is central to modern photonics
      applications ranging from light harvesting to quantum-information processing. To
      this end, nanophotonic waveguides are well suited as they confine photons to a
      one-dimensional geometry and thereby increase the light-matter interaction. In a
      regular waveguide, a quantum emitter interacts equally with photons in either of
      the two propagation directions. This symmetry is violated in nanophotonic
      structures in which non-transversal local electric-field components imply that
      photon emission and scattering may become directional. Here we show that the
      helicity of the optical transition of a quantum emitter determines the direction
      of single-photon emission in a specially engineered photonic-crystal waveguide.
      We observe single-photon emission into the waveguide with a directionality that
      exceeds 90% under conditions in which practically all the emitted photons are
      coupled to the waveguide. The chiral light-matter interaction enables
      deterministic and highly directional photon emission for experimentally
      achievable on-chip non-reciprocal photonic elements. These may serve as key
      building blocks for single-photon optical diodes, transistors and deterministic
      quantum gates. Furthermore, chiral photonic circuits allow the dissipative
      preparation of entangled states of multiple emitters for experimentally
      achievable parameters, may lead to novel topological photon states and could be
      applied for directional steering of light. 

PMID- 26214252
TI  - A monolithic white laser.
AB  - Monolithic semiconductor lasers capable of emitting over the full visible-colour
      spectrum have a wide range of important applications, such as solid-state
      lighting, full-colour displays, visible colour communications and multi-colour
      fluorescence sensing. The ultimate form of such a light source would be a
      monolithic white laser. However, realizing such a device has been challenging
      because of intrinsic difficulties in achieving epitaxial growth of the mismatched
      materials required for different colour emission. Here, we demonstrate a
      monolithic multi-segment semiconductor nanosheet based on a quaternary alloy of
      ZnCdSSe that simultaneously lases in the red, green and blue. This is made
      possible by a novel nanomaterial growth strategy that enables separate control of
      the composition, morphology and therefore bandgaps of the segments. Our nanolaser
      can be dynamically tuned to emit over the full visible-colour range, covering 70%
      more perceptible colours than the most commonly used illuminants. 

PMID- 26214253
TI  - Ballistic Josephson junctions in edge-contacted graphene.
AB  - Hybrid graphene-superconductor devices have attracted much attention since the
      early days of graphene research. So far, these studies have been limited to the
      case of diffusive transport through graphene with poorly defined and modest
      quality graphene/superconductor interfaces, usually combined with small critical
      magnetic fields of the superconducting electrodes. Here, we report graphene-based
      Josephson junctions with one-dimensional edge contacts of molybdenum rhenium. The
      contacts exhibit a well-defined, transparent interface to the graphene, have a
      critical magnetic field of 8 T at 4 K, and the graphene has a high quality due to
      its encapsulation in hexagonal boron nitride. This allows us to study and exploit
      graphene Josephson junctions in a new regime, characterized by ballistic
      transport. We find that the critical current oscillates with the carrier density
      due to phase-coherent interference of the electrons and holes that carry the
      supercurrent caused by the formation of a Fabry-Perot cavity. Furthermore,
      relatively large supercurrents are observed over unprecedented long distances of
      up to 1.5 MUm. Finally, in the quantum Hall regime we observe broken symmetry
      states while the contacts remain superconducting. These achievements open up new
      avenues to exploit the Dirac nature of graphene in interaction with the
      superconducting state. 

PMID- 26214254
TI  - Role of Lipoylation of the Immunodominant Epitope of Pyruvate Dehydrogenase
      Complex: Toward a Peptide-Based Diagnostic Assay for Primary Biliary Cirrhosis.
AB  - Primary biliary cirrhosis is an immune-mediated chronic liver disease whose
      diagnosis relies on the detection of serum antimitochondrial antibodies directed
      against a complex set of proteins, among which pyruvate dehydrogenase complex is
      considered the main autoantigen. We studied the immunological role of the lipoyl
      domain of this protein using synthetic lipoylated peptides, showing that the
      lipoyl chain chirality does not affect autoantibody recognition and, most
      importantly, confirming that both lipoylated and unlipoylated peptides are able
      to recognize specific autoantibodies in patients sera. In fact, 74% of patients
      sera recognize at least one of the tested peptides but very few positive sera
      recognized exclusively the lipoylated peptide, suggesting that the lipoamide
      moiety plays a marginal role within the autoreactive epitope. These results are
      supported by a conformational analysis showing that the lipoyl moiety of pyruvate
      dehydrogenase complex appears to be involved in hydrophobic interactions, which
      may limit its exposition and thus its contribution to the complex antigenic
      epitope. A preliminary analysis of the specificity of the two most active
      peptides indicates that they could be part of a panel of synthetic antigens
      collectively able to mimic in a simple immunoenzymatic assay the complex
      positivity pattern detected in immunofluorescence. 

PMID- 26214255
TI  - The amylase inhibitor montbretin A reveals a new glycosidase inhibition motif.
AB  - The complex plant flavonol glycoside montbretin A is a potent (Ki = 8 nM) and
      specific inhibitor of human pancreatic alpha-amylase with potential as a
      therapeutic for diabetes and obesity. Controlled degradation studies on
      montbretin A, coupled with inhibition analyses, identified an essential high
      affinity core structure comprising the myricetin and caffeic acid moieties linked
      via a disaccharide. X-ray structural analyses of the montbretin A-human alpha
      amylase complex confirmed the importance of this core structure and revealed a
      novel mode of glycosidase inhibition wherein internal pi-stacking interactions
      between the myricetin and caffeic acid organize their ring hydroxyls for optimal
      hydrogen bonding to the alpha-amylase catalytic residues D197 and E233. This
      novel inhibitory motif can be reproduced in a greatly simplified analog, offering
      potential for new strategies for glycosidase inhibition and therapeutic
      development.

PMID- 26214257
TI  - Circular Dichroism in Mass Spectrometry: Quantum Chemical Investigations for the
      Differences between (R)-3-Methylcyclopentanone and Its Cation.
AB  - In mass spectrometry enantiomers can be distinguished by multiphoton ionization
      employing circular polarized laser pulses. The circular dichroism (CD) is
      detected from the normalized difference in the ion yield after excitation with
      light of opposite handedness. While there are cases in which fragment and parent
      ions exhibit the same sign of the CD in the ion yield, several experiments show
      that they might also differ in sign and magnitude. Supported by experimental
      observations it has been proposed that the parent ion, once it has been formed,
      is further excited by the laser, which may result in a change of the CD in the
      ion yield of the formed fragments compared to the parent ion. To gain a deeper
      insight in possible excitation pathways we calculated and compared the electronic
      CD absorption spectra of neutral and cationic (R)-3-methylcyclopentanone,
      applying density functional theory. In addition, electron wavepacket dynamics
      were used to compare the CD of one- and two-photon transitions. Our results
      support the proposed subsequent excitation of the parent ion as a possible origin
      of the difference of the CD in the ion yield between parent ion and fragments.

PMID- 26214256
TI  - Tunable and reversible drug control of protein production via a self-excising
      degron.
AB  - An effective method for direct chemical control over the production of specific
      proteins would be widely useful. We describe small molecule-assisted shutoff
      (SMASh), a technique in which proteins are fused to a degron that removes itself
      in the absence of drug, resulting in the production of an untagged protein.
      Clinically tested HCV protease inhibitors can then block degron removal, inducing
      rapid degradation of subsequently synthesized copies of the protein. SMASh allows
      reversible and dose-dependent shutoff of various proteins in multiple mammalian
      cell types and in yeast. We also used SMASh to confer drug responsiveness onto an
      RNA virus for which no licensed inhibitors exist. As SMASh does not require the
      permanent fusion of a large domain, it should be useful when control over protein
      production with minimal structural modification is desired. Furthermore, as SMASh
      involves only a single genetic modification and does not rely on modulating
      protein-protein interactions, it should be easy to generalize to multiple
      biological contexts.

PMID- 26214258
TI  - Estimation of the error between experimental tetanic force curves of MUs of rat
      medial gastrocnemius muscle and their models by summation of equal successive
      contractions.
AB  - More accurate muscle models require appropriate modelling of individual twitches
      of motor units (MUs) and their unfused tetanic contractions. It was shown in our
      previous papers, using a few MUs, that modelling of unfused tetanic force curves
      by summation of equal twitches is not accurate, especially for slow MUs. The aim
      of this study was to evaluate this inaccuracy using a statistical number of MUs
      of the rat medial gastrocnemius muscle (15 of slow, 15 of fast resistant and 15
      of fast fatigable type). Tetanic contractions were evoked by trains of 41 stimuli
      at random interpulse intervals and different mean frequencies, resembling
      discharge patterns observed during natural muscle activity. The tetanic curves
      were calculated by the summation of equal twitches according to the respective
      experimental patterns. The previously described 6-parameter analytical function
      for twitch modelling was used. Comparisons between the experimental and the
      modelled curves were made using two coefficients: the fit coefficient and the
      area coefficient. The errors between modelled and experimental tetanic forces
      were substantially different between the three MU types. The error was the most
      significant for slow MUs, which develop much higher forces in real contractions
      than could be predicted based on the summation of equal twitches, while the
      smallest error was observed for FF MUs--their recorded tetanic forces were
      similar to those predicted by modelling. The obtained results indicate the
      importance of the inclusion of the type-specific non-linearity in the summation
      of successive twitch-like contractions of MUs in order to increase the
      reliability of modelling skeletal muscle force.

PMID- 26214259
TI  - Cytotoxicity of CdSe-based quantum dots incorporated in glass nanoparticles
      evaluated using human keratinocyte HaCaT cells.
AB  - CdSe quantum dots (QDs) are potential fluorescent reagents, but leakage of Cd and
      Se often induces cytotoxicity. Here we prepared CdSe-based QDs with glass to
      reduce their leakage and examined their cytotoxicity using keratinocyte cells.
      The cytotoxicity of the QDs with glass was obviously lower than that of the
      commercial QDs with polymer, suggesting their safety for biological applications.

PMID- 26214260
TI  - Developing measures for information ergonomics in knowledge work.
AB  - Information ergonomics is an evolving application domain of ergonomics focusing
      on the management of workload in the real-world contexts of information-intensive
      tasks. This study introduces a method for the evaluation of information
      ergonomics in knowledge work. To this end, five key dimensions of information
      ergonomics were identified: contextual factors of knowledge work, multitasking,
      interruptions at work, practices for managing information load, and perceived job
      control and productivity. In total, 24 measures focusing on the above dimensions
      were constructed. The measures include, for example, the number of fragmented
      work tasks per work day. The measures were preliminarily tested in two Finnish
      organisations, making use of empirical data gathered by interviews, electronic
      questionnaires and log data applications tracking work processes on personal
      computers. The measures are applicable to the evaluation of information
      ergonomics, even though individual measures vary with regard to the amount of
      work and time needed for data analysis. Practitioner Summary: The study
      introduces a method for the evaluation of information ergonomics in knowledge
      work. To this end, 24 measures were constructed and tested empirically. The
      measures focus on contextual factors of knowledge work, multitasking,
      interruptions at work, practices for managing information load, and perceived job
      control and productivity. 

PMID- 26214261
TI  - Membrane-Sugar Interactions Probed by Pulsed Electron Paramagnetic Resonance of
      Spin Labels.
AB  - Sugars can stabilize biological systems under extreme desiccation and freezing
      conditions. Hypothetical molecular mechanisms suggest that the stabilization
      effect may be determined either by specific interactions of sugars with
      biological molecules or by the influence of sugars on the solvating shell of the
      biomolecule. To explore membrane-sugar interactions, we applied electron spin
      echo envelope modulation (ESEEM) spectroscopy, a pulsed version of electron
      paramagnetic resonance (EPR), to phospholipid bilayers with spin-labeled lipids
      added and solvated by aqueous deuterated sucrose and trehalose solutions. The
      phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). The spin
      labeled lipids were 1,2-dipalmitoyl-sn-glycero-3-phospho(TEMPO)choline (T-PCSL),
      with spin-label TEMPO at the lipid polar headgroup. The deuterium ESEEM amplitude
      was calibrated using known concentrations of glassy deuterated sugar solvents.
      The data obtained indicated that the sugar concentration near the membrane
      surface obeyed a simple Langmuir model of monolayer adsorption, which assumes
      direct sugar-molecule bonding to the bilayer surface. 

PMID- 26214262
TI  - beta-Sarcoglycan gene transfer decreases fibrosis and restores force in LGMD2E
      mice.
AB  - Limb-girdle muscular dystrophy type 2E (LGMD2E) results from mutations in the
      beta-sarcoglycan (SGCB) gene causing loss of functional protein and concomitant
      loss of dystrophin-associated proteins. The disease phenotype is characterized by
      muscle weakness and wasting, and dystrophic features including muscle fiber
      necrosis, inflammation and fibrosis. The Sgcb-null mouse recapitulates the
      clinical phenotype with significant endomysial fibrosis providing a relevant
      model to test whether gene replacement will be efficacious. We directly addressed
      this question using a codon optimized human beta-sarcoglycan gene (hSGCB) driven
      by a muscle-specific tMCK promoter (scAAVrh74.tMCK.hSGCB). Following isolated
      limb delivery (5 * 10(11) vector genome (vg)), 91.2% of muscle fibers in the
      lower limb expressed beta-sarcoglycan, restoring assembly of the sarcoglycan
      complex and protecting the membrane from Evans blue dye leakage. Histological
      outcomes were significantly improved including decreased central nucleation,
      normalization of muscle fiber size, decreased macrophages and inflammatory
      mononuclear cells, and an average of a 43% reduction in collagen deposition in
      treated muscle compared with untreated muscle at end point. These measures
      correlated with improvement of tetanic force and resistance to eccentric
      contraction. In 6-month-old mice, as indicated by collagen staining,
      scAAVrh74.tMCK.hSGCB treatment reduced fibrosis by 42%. This study demonstrates
      the potential for gene replacement to reverse debilitating fibrosis, typical of
      muscular dystrophy, thereby providing compelling evidence for movement to
      clinical gene replacement for LGMD2E. 

PMID- 26214263
TI  - POZylation: a new approach to enhance nanoparticle diffusion through mucosal
      barriers.
AB  - The increasing use of nanoparticles in the pharmaceutical industry is generating
      concomitant interest in developing nanomaterials that can rapidly penetrate into,
      and permeate through, biological membranes to facilitate drug delivery and
      improve the bioavailability of active pharmaceutical ingredients. Here, we
      demonstrate that the permeation of thiolated silica nanoparticles through porcine
      gastric mucosa can be significantly enhanced by their functionalization with
      either 5 kDa poly(2-ethyl-2-oxazoline) or poly(ethylene glycol). Nanoparticle
      diffusion was assessed using two independent techniques; Nanoparticle Tracking
      Analysis, and fluorescence microscopy. Our results show that poly(2-ethyl-2
      oxazoline) and poly(ethylene glycol) have comparable abilities to enhance
      diffusion of silica nanoparticles in mucin dispersions and through the gastric
      mucosa. These findings provide a new strategy in the design of nanomedicines, by
      surface modification or nanoparticle core construction, for enhanced transmucosal
      drug delivery. 

PMID- 26214264
TI  - Theoretical studies of molecular orientation and charge recombination in poly
      paraphenylenevinylene light-emitting diodes.
AB  - Poly-paraphenylenevinylene (PPV), a material used in organic light-emitting
      diodes (OLEDs), for which improving the efficiency is an important issue. In
      general, the molecular orientations of organic compounds in the crystal form are
      an essential factor determining electron and hole transfer, which are closely
      related to the efficiency of OLEDs. We have investigated the effects of the
      rotation of each molecule and the intermolecular distance in the dimer system of
      PPV, which consists of donor and acceptor molecules, on its charge-recombination
      process by performing constrained density functional calculations. Starting from
      the structure of the crystal, it was clarified that the rotation of the donor
      decreases the charge-recombination factor, to nearly zero, while that of the
      acceptor increases it to about 10(6) s(-1). We found that this is caused by the
      repulsive interaction between the donor and acceptor molecules and the formation
      of a transport pathway resulting from the acceptor rotation. 

PMID- 26214265
TI  - Older Adults' Uptake and Adherence to Exercise Classes: Instructors'
      Perspectives.
AB  - Exercise classes provide a range of benefits for older adults, but adherence
      levels are poor. We know little of instructors' experiences of delivering
      exercise classes to older adults. Semistructured interviews, informed by the
      Theory of Planned Behavior (TPB), were conducted with instructors (n = 19)
      delivering multicomponent exercise classes to establish their perspectives on
      older adults' uptake and adherence to exercise classes. Analysis revealed
      'barriers' to uptake related to identity, choice/control, cost, and venue, and
      'solutions' included providing choice/control, relating exercise to identity, a
      personal touch, and social support. Barriers to adherence included unrealistic
      expectations and social influences, and solutions identified were encouraging
      commitment, creating social cohesion, and an emphasis on achieving outcomes.
      Older adults' attitudes were an underlying theme, which related to all barriers
      and solutions. The instructor plays an important, but not isolated, role in older
      adults' uptake and adherence to classes. Instructors' perspectives help us to
      further understand how we can design successful exercise classes. 

PMID- 26214266
TI  - Mepolizumab versus placebo for asthma.
AB  - BACKGROUND: Mepolizumab is a human monoclonal antibody against interleukin-5 (IL
      5), the main cytokine involved in the activation of eosinophils, which in turn
      causes airway inflammation. Recent studies have suggested these agents may have a
      role in reducing exacerbations and improving health-related quality of life
      (HRQoL). There are no recommendations for the use of mepolizumab in adults or
      children in the recent update of the BTS/SIGN guidelines (BTS/SIGN 2014).
      OBJECTIVES: To compare the effects of mepolizumab with placebo on exacerbations
      and HRQoL in adults and children with chronic asthma. SEARCH METHODS: We searched
      the Cochrane Airways Group Register (CAGR) of trials, clinical trial registries,
      manufacturers' websites and the reference lists of included studies. Searches
      were conducted in November 2013 and updated in November 2014. SELECTION CRITERIA:
      We included randomised controlled trials comparing mepolizumab versus placebo in
      adults and children with asthma. DATA COLLECTION AND ANALYSIS: Two authors
      independently extracted data and analysed outcomes using a random-effects model.
      We used standard methods expected by The Cochrane Collaboration. MAIN RESULTS:
      Eight studies on 1707 participants met the inclusion criteria. Only two studies
      included children (over 12 years of age), but they did not report separate
      findings for the adolescents. Seven studies involved intravenous mepolizumab
      alone; one included a subcutaneous arm. There was heterogeneity in the severity
      and clinical pattern of asthma among the participants in the eight studies,
      varying from mild to moderate atopic asthma, to persistent asthma and
      eosinophilic asthma with recurrent exacerbations. Selection bias was a concern in
      several of the studies included in this review.Four trials compared intravenous
      mepolizumab to placebo in relation to HRQoL. Two studies measured scores from the
      Asthma Quality of Life Questionnaire (AQLQ), which showed a non-significant
      difference between mepolizumab and placebo (mean difference (MD) 0.21, 95%
      confidence interval (CI) - 0.01 to 0.44; participants = 682), in the direction
      favouring mepolizumab. The third study used the St. George's Respiratory
      Questionnaire (SGRQ) and found a significant difference between mepolizumab and
      placebo (MD 6.40, 95% CI 3.15 to 9.65; participants = 576), which indicated a
      clinically important benefit favouring mepolizumab. A fourth study noted that
      there was no significant difference but did not provide any data. The two studies
      in people with eosinophilic asthma showed a reduction in clinically significant
      exacerbation rates (Risk Ratio 0.52, 95% CI 0.43 to 0.64; participants = 690).
      However, an analysis of four studies that were not confined to people with
      eosinophilic asthma indicated considerable heterogeneity and no significant
      difference in people with one or more exacerbations between mepolizumab and
      placebo using a random-effects model (Risk Ratio 0.67, 95% CI 0.34 to 1.31;
      participants = 468; I(2) = 59%).The analysis of serious adverse events indicated
      a significant difference favouring mepolizumab (Risk ratio 0.49, 95% CI 0.30 to
      0.80; participants = 1441; studies = 5; I(2) = 0%). It was not possible to
      combine the results for adverse events, and we deemed the quality of this
      evidence to be low.A single study compared subcutaneous mepolizumab to placebo in
      385 adults with severe eosinophilic asthma and found an improvement in HRQoL
      scores and a reduction in asthma exacerbations, including exacerbations requiring
      admission to hospital. AUTHORS' CONCLUSIONS: It is not possible to draw firm
      conclusions from this review with respect to the role of mepolizumab in patients
      with asthma. Our confidence in the results of this review are limited by the fact
      that the intravenous route is not currently licensed for mepolizumab, and the
      evidence for the currently licenced subcutaneous route is limited to a single
      study in participants with severe eosinophilic asthma.The currently available
      studies provide evidence that mepolizumab can lead to an improvement in health
      related quality of life scores and reduce asthma exacerbations in people with
      severe eosinophilic asthma.Further research is needed to clarify which subgroups
      of patients with asthma could potentially benefit from this treatment. Dosage,
      ideal dosing regimens and duration of treatment need to be clarified, as the
      studies included in this review differed in their protocols. There are no studies
      reporting results from children, so we cannot comment on treatment for this age
      group. At the present time, larger studies using licenced treatment regimens are
      required to establish the role of mepolizumab in the treatment of severe asthma.

PMID- 26214267
TI  - Investigation of neurotrophic factor concentrations with a novel in vitro concept
      for peripheral nerve regeneration.
AB  - The regeneration of nerves of the peripheral nervous system after injuries is a
      complex process. This study presents a novel in vitro neurite regeneration
      concept to investigate the regeneration of neurons and their processes with
      different concentrations of neurotrophic factors. The core part of the concept is
      a transparent microfluidic neurite isolation (NI) device affixed on top of a
      microelectrode array (MEA), providing a fast and easy way to assess both the
      growth and the electrical activity of neurites. The NI-MEA isolates neurites from
      the culture with microchannels that serve as guidance tubes, equipped with
      microelectrodes. Thus, the NI-MEA allows neurite growth, as observed by
      microscopy, to be correlated with neurite electrical activity, as measured by
      electrophysiological recordings. To demonstrate proof of concept of neurite
      regeneration, we cultured cells from the superior cervical ganglion of postnatal
      mice under different concentrations of nerve growth factor (NGF). During the
      regeneration process, we observed an increase in the number of neurites entering
      the microchannels along with an increase in spike activity recorded by the
      microelectrodes in the microchannels. We also observed a concentration-dependent
      effect of neurotrophic factor on the excitability of the growing neurites, with
      neurites bathed in 20 ng/ml NGF exhibiting enhanced early growth. Thus, our
      neurite regeneration concept with the NI-MEA device allows further study of
      neurotrophic factors and reduces the requirement for in vivo experiments on the
      regeneration of peripheral nerves after injury.

PMID- 26214268
TI  - Probing protease sensitivity of recombinant human erythropoietin reveals alpha3
      alpha4 inter-helical loop as a stability determinant.
AB  - Although unglycosylated HuEpo is fully functional, it has very short serum half
      life. However, the mechanism of in vivo clearance of human Epo (HuEpo) remains
      largely unknown. In this study, the relative importance of protease-sensitive
      sites of recombinant HuEpo (rHuEpo) has been investigated by analysis of
      structural data coupled with in vivo half-life measurements. Our results identify
      alpha3-alpha4 inter-helical loop region as a target site of lysosomal protease
      Cathepsin L. Consistent with previously-reported lysosomal degradation of HuEpo,
      these results for the first time identify cleavage sites of rHuEpo by specific
      lysosomal proteases. Furthermore, in agreement with the lowered exposure of the
      peptide backbone around the cleavage site, remarkably substitutions of residues
      with bulkier amino acids result in significantly improved in vivo stability.
      Together, these results have implications for the mechanism of in vivo clearance
      of the protein in humans.

PMID- 26214269
TI  - Effective Treatment for Rapid Improvement of Both Disease Activity and Self
      Reported Physical Activity in Early Rheumatoid Arthritis.
AB  - OBJECTIVE: To investigate the longitudinal relationship between disease activity
      and self-reported physical activity (PA) in patients with early rheumatoid
      arthritis during the first year of treatment with combination therapy. METHODS:
      PA was measured with the Short Questionnaire to Assess Health-Enhancing Physical
      Activity at baseline, 13 weeks, 26 weeks, and 52 weeks after start of treatment
      in the context of the Combinatietherapie Bij Reumatoide Artritis-Light trial. The
      reported PA classified patients as meeting or not meeting the World Health
      Organization (WHO) PA guideline (cutoff: 150 minutes of moderate-to-intense
      activity per week). Other measurements included the Disease Activity Score (DAS).
      Since both treatment arms showed equal treatment effect, these were analyzed as 1
      group with simple before-after analyses and generalized estimating equations
      (GEE). RESULTS: In these analyses, 140 patients (86% of the trial population, 66%
      women, mean age 52 years) with complete data were included. At entry, 69% of the
      patients met the WHO PA guideline, increasing to 90% at week 13, and remaining
      stable at 89% after 1 year (P < 0.001). Mean DAS improved from 4.0 to 1.8 during
      the first year of treatment (P < 0.001). In GEE analyses, DAS decreases were
      significantly associated with PA increases (P = 0.008). Patients with clinically
      relevant responses (expressed as DAS remission, European League Against
      Rheumatism good response or American College of Rheumatology criteria for 70%
      improvement response) showed higher PA levels compared to nonresponders,
      regardless of the definition of response, for both the WHO and Dutch PA
      guideline. CONCLUSION: Early rheumatoid arthritis patients using combination
      therapy improved both disease activity and PA, a beneficial effect persisting for
      at least 1 year.

PMID- 26214270
TI  - The Concern for Supply-Sensitive Neonatal Intensive Care Unit Care: If You Build
      Them, They Will Come.

PMID- 26214271
TI  - Encapsulating Inorganic Acetylene, HBNH, Using Flanking Coordinative
      Interactions.
AB  - A stable donor-acceptor coordination complex of the elusive parent inorganic
      iminoborane HBNH (a structural analogue of acetylene) is reported. This species
      was generated via thermally induced N2 elimination/1,2-H migration from a
      hydrido(azido)borane adduct NHC?BH2N3 (NHC=N-heterocyclic carbene) in the
      presence of a fluorinated triarylborane. The mechanism of this process was also
      investigated by computational and isotopic labeling studies. This transformation
      represents a new and potentially modular route to unsaturated inorganic building
      blocks for advanced material synthesis.

PMID- 26214272
TI  - Immobilization of a molecular cobalt electrocatalyst by hydrophobic interaction
      with a hematite photoanode for highly stable oxygen evolution.
AB  - A unique modification of a hematite photoanode with perfluorinated Co
      phthalocyanine (CoFPc) by strong binding associated with hydrophobic interaction
      is demonstrated. The resultant molecular electrocatalyst - a hematite photoanode
      hybrid material showed a significant onset shift and high stability for the
      photoelectrochemical oxidation evolution reaction (OER). 

PMID- 26214273
TI  - Disclosure of Boxed Warnings to Research Participants.

PMID- 26214274
TI  - Exploring the Properties of Genetically Engineered Silk-Elastin-Like Protein
      Films.
AB  - Free standing films of a genetically engineered silk-elastin-like protein (SELP)
      were prepared using water and formic acid as solvents. Exposure to methanol
      saturated air promoted the formation of aggregated beta-strands rendering aqueous
      insolubility and improved the mechanical properties leading to a 10-fold increase
      in strain-to-failure. The films were optically clear with resistivity values
      similar to natural rubber and thermally stable up to 180  degrees C. Addition of
      glycerol showed to enhance the flexibility of SELP/glycerol films by interacting
      with SELP molecules through hydrogen bonding, interpenetrating between the
      polymer chains and granting more conformational freedom. This detailed
      characterization provides cues for future and unique applications using SELP
      based biopolymers.

PMID- 26214275
TI  - Experimental approach to the fundamental limit of the extinction coefficients of
      ultra-smooth and highly spherical gold nanoparticles.
AB  - The theoretical extinction coefficients of gold nanoparticles (AuNPs) have been
      mainly verified by the analytical solving of the Maxwell equation for an ideal
      sphere, which was firstly founded by Mie (generally referred to as Mie theory).
      However, in principle, it has not been directly feasible with experimental
      verification especially for relatively large AuNPs (i.e., >40 nm), as
      conventionally proposed synthetic methods have inevitably resulted in a polygonal
      shaped, non-ideal Au nanosphere. Here, mono-crystalline, ultra-smooth, and highly
      spherical AuNPs of 40-100 nm were prepared by the procedure reported in our
      recent work (ACS Nano, 2013, 7, 11064). The extinction coefficients of the
      ideally spherical AuNPs of 40-100 nm were empirically extracted using the Beer
      Lambert law, and were then compared with the theoretical limits obtained by the
      analytical and numerical methods. The obtained extinction coefficients of the
      ideally spherical AuNPs herein agree much more closely with the theoretical
      limits, compared with those of the faceted or polygonal shaped AuNPs. In
      addition, in order to further elucidate the importance of being spherical, we
      systematically compared our ideally spherical AuNPs with the polygonal
      counterparts; effectively addressing the role of the surface morphology on the
      spectral responses in both theoretical and experimental manners. 

PMID- 26214277
TI  - New faces of porous Prussian blue: interfacial assembly of integrated hetero
      structures for sensing applications.
AB  - Prussian blue (PB), the oldest synthetic coordination compound, is a classic and
      fascinating transition metal coordination material. Prussian blue is based on a
      three-dimensional (3-D) cubic polymeric porous network consisting of alternating
      ferric and ferrous ions, which provides facile assembly as well as precise
      interaction with active sites at functional interfaces. A fundamental
      understanding of the assembly mechanism of PB hetero-interfaces is essential to
      enable the full potential applications of PB crystals, including chemical
      sensing, catalysis, gas storage, drug delivery and electronic displays.
      Developing controlled assembly methods towards functionally integrated hetero
      interfaces with adjustable sizes and morphology of PB crystals is necessary. A
      key point in the functional interface and device integration of PB nanocrystals
      is the fabrication of hetero-interfaces in a well-defined and oriented fashion on
      given substrates. This review will bring together these key aspects of the hetero
      interfaces of PB nanocrystals, ranging from structure and properties, interfacial
      assembly strategies, to integrated hetero-structures for diverse sensing. 

PMID- 26214276
TI  - Genetic Modifiers of Age at Onset in Carriers of the G206A Mutation in PSEN1 With
      Familial Alzheimer Disease Among Caribbean Hispanics.
AB  - IMPORTANCE: The present study identified potential genetic modifiers that may
      delay or accelerate age at onset of familial Alzheimer disease (AD) by examining
      age at onset in PSEN1 mutation carrier families, and further investigation of
      these modifiers may provide insight into the pathobiology of AD and potential
      therapeutic measures. OBJECTIVE: To identify genetic variants that modify age at
      onset of AD. DESIGN, SETTING, AND PARTICIPANTS: Using a subset of Caribbean
      Hispanic families that carry the PSEN1 p.G206A mutation, we performed a 2-stage
      genome study. The mutation carrier families from an ongoing genetic study served
      as a discovery set, and the cohort of those with LOAD served as a confirmation
      set. To identify candidate loci, we performed linkage analysis using 5 p.G206A
      carrier families (n = 56), and we also performed whole-exome association analysis
      using 31 p.G206A carriers from 26 families. To confirm the genetic modifiers
      identified from the p.G206A carrier families, we analyzed the GWAS data for 2888
      elderly individuals with LOAD. All study participants were Caribbean Hispanics.
      MAIN OUTCOMES AND MEASURES: Age at onset of AD. RESULTS: Linkage analysis of AD
      identified the strongest linkage support at 4q35 (LOD [logarithm of odds] score,
      3.69), and the GWAS of age at onset identified variants on 1p13.1, 2q13, 4q25,
      and 17p11. In the confirmation stage, genewise analysis identified SNX25, PDLIM3,
      and 3 SH3 domain genes (SORBS2, SH3RF3, and NPHP1) to be significantly associated
      with LOAD. Subsequent allelic association analysis confirmed SNX25, PDLIM3, and
      SORBS2 as genetic modifiers of age at onset of EOAD and LOAD and provided modest
      support for SH3RF3 and NPHP1. CONCLUSIONS AND RELEVANCE: Our 2-stage analysis
      revealed that SNX25, PDLIM3, and SORBS2 may serve as genetic modifiers of age at
      onset in both EOAD and LOAD.

PMID- 26214278
TI  - Wispy and Orb cooperate in the cytoplasmic polyadenylation of localized gurken
      mRNA.
AB  - BACKGROUND: In Drosophila, the dorsal-ventral (D-V) axis of the oocyte is
      dependent on Gurken (Grk) protein distribution. This is achieved through the
      cytoplasmic localization of grk mRNA and regulation of its translation. During
      mid-late stages of oogenesis, grk mRNA and protein are localized to the dorsal
      anterior of the oocyte, while unlocalized grk transcripts are translationally
      silenced. As females carrying mutations in the gene encoding the CPEB protein Orb
      lay ventralized eggs due to insufficient Grk levels, it seemed likely that
      cytoplasmic polyadenylation of grk transcripts may play a role in their
      translational regulation. RESULTS: We have found that grk is polyadenylated
      throughout oogenesis, with poly(A) tails of approximately 30-50 A residues.
      Hyperadenylated grk transcripts, with poly(A) tails of 50-90 As, are detected in
      late stage egg chambers, but they fail to accumulate in oocytes deficient in Orb
      or the poly(A) polymerase Wispy (Wisp). wisp females also lay weakly ventralized
      eggs, demonstrating that they produce inadequate amounts of Grk. Finally,
      unlocalized grk transcripts are also not appropriately hyperadenylated.
      CONCLUSIONS: Localized cytoplasmic polyadenylation of grk mRNA by Wisp and Orb is
      necessary to achieve appropriate Grk protein accumulation in the D/A corner of
      the oocyte during mid to late oogenesis.

PMID- 26214279
TI  - An enantioselective organocatalyzed aza-Morita-Baylis-Hillman reaction of isatin
      derived ketimines with acrolein.
AB  - A highly enantioselective aza-Morita-Baylis-Hillman (aza-MBH) reaction of isatin
      derived ketimines with acrolein was established using beta-isocupreidine (beta
      ICD) or alpha-isocupreine (alpha-ICPN) as a chiral acid-base organocatalyst. The
      present protocol readily furnished (S) or (R)-aza-MBH adducts with a chiral
      tetrasubstituted carbon stereogenic center in up to 98% ee. 

PMID- 26214280
TI  - A fast self-cleaning SERS-active substrate based on an inorganic-organic hybrid
      nanobelt film.
AB  - Surface-enhanced Raman scattering (SERS) spectroscopy, as a robust and attractive
      spectroscopic technique, has been widely used for the unequivocal identification
      of analytes, and an ideal SERS substrate that is highly sensitive and
      reproducible. Currently, existing substrates usually exhibit substantial
      sensitivity, however, achieve recyclable utilization through multi-step and
      complex procedures with the prerequisite of external facilities. Herein, an
      inorganic-organic hybrid nanobelt film assembled by novel Ag@Ag(DMSO)xCl
      nanobelts was proposed as an active SERS substrate. This unique substrate
      exhibits highly sensitive SERS detection properties, and realizes ultrafast self
      cleaning by in situ photocatalytic degradation of targeted molecules adsorbed
      onto the film during the detection process, showing the potential for real-time
      online monitoring. Our study demonstrates a new concept for preparing an in situ
      self-cleaning substrate by the rational design and assembly of special
      nanomaterials. 

PMID- 26214281
TI  - Solution-driven approaches to generic substitution challenges - a survey among
      international experts.
AB  - The main objective of this study was to explore the perception and understanding
      of economic, legal, and social barriers that may restrain generic uptake among
      recognized international experts in health care, and to identify and verify
      recommendations on how to streamline generic substitution (GS) at no expense of
      therapeutic safety. A questionnaire survey was devised, and experts with world
      renowned expertise in the field of generic medicinal products were selected.
      Almost 3/4 of respondents claimed that all drugs that satisfy bioequivalence
      criteria represent similar efficacy and adverse effects, and 1/4 of respondents
      believed that some differences could be reported. The majority of experts
      supported (i) the right of patients to refuse GS, (ii) the right of physicians to
      veto GS, and (iii) the introduction of a statutory obligation to provide patients
      with access to the cheapest generics available on the market. The main obstacles
      to more general uptake of generics were as follows: (i) perception of generics as
      lower quality products, (ii) absence of a transparent policy governing GS, and
      (iii) disincentives to pharmacists and physicians. Among the most popular
      recommendations were as follows: (i) introduction of various measures to aid
      physicians in generic prescribing, (ii) setting clear guidelines specifying when
      GS is not advisable, (iii) supporting competition on the generic market. The
      views of experts and the resulting recommendations were strongly affected by
      their opinion on the bioequivalence of generics. From this analysis, we have
      selected several principal recommendations which could help shape successful
      healthcare policies regarding GS. 

PMID- 26214282
TI  - From gene to harvest: insights into upstream process development for the GMP
      production of a monoclonal antibody in transgenic tobacco plants.
AB  - The EU Sixth Framework Programme Integrated Project 'Pharma-Planta' developed an
      approved manufacturing process for recombinant plant-made pharmaceutical proteins
      (PMPs) using the human HIV-neutralizing monoclonal antibody 2G12 as a case study.
      In contrast to the well-established Chinese hamster ovary platform, which has
      been used for the production of therapeutic antibodies for nearly 30 years, only
      draft regulations were initially available covering the production of recombinant
      proteins in transgenic tobacco plants. Whereas recombinant proteins produced in
      animal cells are secreted into the culture medium during fermentation in
      bioreactors, intact plants grown under nonsterile conditions in a glasshouse
      environment provide various 'plant-specific' regulatory and technical challenges
      for the development of a process suitable for the acquisition of a manufacturing
      licence for clinical phase I trials. During upstream process development, several
      generic steps were addressed (e.g. plant transformation and screening, seed bank
      generation, genetic stability, host plant uniformity) as well as product-specific
      aspects (e.g. product quantity). This report summarizes the efforts undertaken to
      analyse and define the procedures for the GMP/GACP-compliant upstream production
      of 2G12 in transgenic tobacco plants from gene to harvest, including the design
      of expression constructs, plant transformation, the generation of production
      lines, master and working seed banks and the detailed investigation of
      cultivation and harvesting parameters and their impact on biomass, product yield
      and intra/interbatch variability. The resulting procedures were successfully
      translated into a prototypic manufacturing process that has been approved by the
      German competent authority.

PMID- 26214283
TI  - Development of a PtSn bimetallic catalyst for direct fuel cells using bio-butanol
      fuel.
AB  - Pt and PtSn catalysts were studied for n-butanol electro-oxidation at various
      temperatures. PtSn showed a higher activity towards butanol electro-oxidation
      compared to Pt in acidic media. The onset potential for n-butanol oxidation on
      PtSn is ~520 mV lower than that found on Pt, and significantly lower activation
      energy was found for PtSn compared with that for Pt. 

PMID- 26214284
TI  - alpha-tocopherol decreases interleukin-1beta and -6 and increases human beta
      defensin-1 and -2 secretion in human gingival fibroblasts stimulated with
      Porphyromonas gingivalis lipopolysaccharide.
AB  - BACKGROUND AND OBJECTIVE: Periodontitis, a disease associated with chronic
      inflammation, results in significant destruction of periodontal tissues.
      Uncontrolled, periodontal disease negatively affects general patient health. We
      sought to evaluate the effect of alpha-tocopherol on gingival fibroblast behavior
      following exposure to Porphyromonas gingivalis lipopolysaccharide (LPS). MATERIAL
      AND METHODS: Primary human gingival fibroblasts were cultured for 24 and 48 h
      with alpha-tocopherol at various concentrations (0, 50, 100 and 200 MUm) in the
      presence or absence of 1 MUg/mL of LPS. At the end of each time point, cell
      adhesion and growth were evaluated by means of optical microscope observations
      and MTT assay. The secretion levels of cytokines interleukin (IL)-1beta and IL-6
      and human beta-defensins 1 and 2 were measured by specific enzyme-linked
      immunosorbent assay. Finally, an in vitro scratch wound assay was performed to
      investigate the effect of alpha-tocopherol on fibroblast migration. RESULTS:
      alpha-tocopherol alone had no adverse effect on cell adhesion and morphology.
      Fibroblast proliferation increased in the presence of alpha-tocopherol with and
      without LPS. alpha-tocopherol alone had no effect on inflammatory cytokine (IL
      1beta and IL-6) secretion. Interestingly, following cell exposure to P.
      gingivalis LPS, alpha-tocopherol significantly (p < 0.01) decreased the secretion
      of these two cytokines and increased human beta-defensin-1 and -2 secretion.
      Finally, alpha-tocopherol increased the healing rate of the gingival fibroblasts
      from 12 h up to 48 h. CONCLUSION: These results suggest that alpha-tocopherol may
      play an active role in countering the damaging effect of LPS by reducing
      inflammatory cytokines, increasing beta-defensins and promoting fibroblast
      growth, migration and wound healing.

PMID- 26214285
TI  - No association between vitamin D and atopy, asthma, lung function or atopic
      dermatitis: a prospective study in adults.
AB  - Studies suggest that vitamin D may be involved in the pathogenesis of allergic
      disorders, asthma and decreased lung function. However, results are inconsistent
      and only few prospective studies have examined adults. The purpose of this study
      was to investigate the association of serum 25-hydroxy vitamin D (s25(OH)D) with
      atopy, atopic dermatitis (AD), asthma, wheezing and impaired lung function in a
      prospective study of Danish adults. A random sample of 3471 persons was examined
      in 2006-2008. Of these, 2308 were re-examined 5 years later. s25(OH)D and
      specific IgE against four common inhalant allergens were measured by standard
      procedures. Wheezing, asthma and AD were assessed from questionnaires and lung
      function was measured by spirometry. We found no statistically significant
      associations between s25(OH)D and prevalence or incidence of atopy, AD, asthma or
      wheezing. Associations with lung function were inconsistent. We conclude that
      vitamin D status does not influence these conditions in adults.

PMID- 26214286
TI  - Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12
      creates an additive effect on bone formation onset and volume.
AB  - Bone morphogenetic protein-2 (BMP-2) gene delivery has shown to induce bone
      formation in vivo in cell-based tissue engineering. In addition, the
      chemoattractant stromal cell-derived factor-1alpha (SDF-1alpha, also known as
      CXCL12) is known to recruit multipotent stromal cells towards its release site
      where it enhances vascularisation and possibly contributes to osteogenic
      differentiation. To investigate potential cooperative behaviour for bone
      formation, we investigated combined release of BMP-2 and SDF-1alpha on ectopic
      bone formation in mice. Multipotent stromal cell-seeded and cell-free constructs
      with BMP-2 plasmid DNA and /or SDF-1alpha loaded onto gelatin microparticles,
      were implanted subcutaneously in mice for a period of 6 weeks. Histological
      analysis and histomorphometry revealed that the onset of bone formation and the
      formed bone volume were both enhanced by the combination of BMP-2 and SDF-1alpha
      compared to controls in cell-seeded constructs. Samples without seeded
      multipotent stromal cells failed to induce any bone formation. We conclude that
      the addition of stromal cell-derived factor-1alpha to a cell-seeded alginate
      based bone morphogenetic protein-2 plasmid DNA construct has an additive effect
      on bone formation and can be considered a promising combination for bone
      regeneration. 

PMID- 26214287
TI  - Evolving concepts of chondrogenic differentiation: history, state-of-the-art and
      future perspectives.
AB  - As a cell source, multipotent mesenchymal stromal cells or mesenchymal stem cells
      (MSCs) are promising candidates for chondrogenic differentiation and subsequent
      cartilage regeneration. From previous literature, it is known that chondrogenic
      differentiation of MSCs inevitably leads to hypertrophy and subsequent
      endochondral ossification. In this review, we examine the history of currently
      established protocols of chondrogenic differentiation and elaborate on the roles
      of individual components of chondrogenic differentiation medium. We also
      summarise the effects of physical, chemical and biological factors involved, and
      propose potential strategies to differentiate MSCs into articular chondrocytes
      with homogenous mature phenotypes through spatial-temporal incorporation of cell
      differentiation and chondrogenesis. 

PMID- 26214288
TI  - In vivo effect of immobilisation of bone morphogenic protein 2 on titanium
      implants through nano-anchored oligonucleotides.
AB  - The aim of the present study was to test the hypothesis that immobilisation of
      bone morphogenic proteins on the surface of titanium implants through nano
      anchored oligonucleotides can enhance peri-implant bone formation. Non-coding 60
      mer DNA oligonucleotides (ODN) were anchored to the surface of custom made
      sandblasted acid etched (SAE) titanium screw implants through anodic
      polarisation, gamma-sterilised with a standard dose of 25 kGy, and were
      hybridised with complementary 30-mer strands of DNA oligonucleotides conjugated
      to rhBMP2. Blank SAE implants, SAE implants with nano-anchored ODN and SAE
      implants with nano-anchored ODN and non-conjugated rhBMP2 served as controls. The
      implants were inserted into the tibiae of 36 Sprague Dawley rats. Perforations at
      the head and the tip of the implants allowed for bone ingrowth. Bone ingrowth
      into perforations and bone implant contact (BIC) as well as bone density (BD) at
      a distance of 200 um from the implant surface were assessed after 1 , 4 and 13
      weeks. Implants with nano-anchored ODN strands hybridised with conjugated rhBMP2
      exhibited enhanced bone ingrowth into the perforations and increased BIC after 1
      week as well as increased BIC after 4 weeks compared to controls. No difference
      was seen after 13 weeks. Bone density around the outer implant surface did not
      differ significantly at any of the intervals. It is concluded that rhBMP2
      immobilised on the surface of titanium implants through nano-anchored
      oligonucleotide strands can enhance bone implant contact. The conditions of
      sterilisation tested allowed for handling under clinically relevant conditions.

PMID- 26214289
TI  - TIPS to manipulate myogenesis: retention of myoblast differentiation capacity
      using microsphere culture.
AB  - Cell therapy is an emerging option for regenerating skeletal muscle. Improved
      delivery methods for anchorage-dependent myoblasts are likely to improve
      integration and function of transplanted muscle cells. Highly porous
      microspheres, produced using thermally induced phase separation (TIPS), have
      features ideally suited for minimally invasive cell delivery. The purpose of this
      study was to investigate, for the first time, the use of TIPS microspheres as
      highly porous microcarriers for manipulation of human skeletal muscle myoblasts
      (HSMM) under defined culture conditions. HSMM cells readily attached to the
      surface of poly (DL-lactide-co-glycolide) (PLGA) TIPS microcarriers, where they
      were induced to continue proliferating or to be driven towards differentiation
      whilst under static-dynamic culture conditions for 7 days. Switching from
      proliferation medium to differentiation medium for 7 days, resulted in increased
      protein expression of skeletal muscle cell contractile apparatus components, MyoD
      and skeletal muscle myosin heavy chain, compared with cells cultured on
      conventional culture plasticware for the same duration (p < 0.001). Growth of
      myoblasts on the surface of the microcarriers and their migration following
      simulated delivery, caused no change to the proliferative capacity of cells over
      7 days. Results from this study demonstrate that TIPS microspheres provide an
      ideal vehicle for the expansion and delivery of myoblasts for therapeutic
      applications. Transplantation of myoblasts anchored to a substrate, rather than
      in suspension, will reduce the amount of ex vivo manipulation required during
      preparation of the product and allows cells to be delivered in a more natural
      state. This will improve the ability to control cell dosage and increase the
      likelihood of efficacy.

PMID- 26214290
TI  - Charge Transfer and Orbital Reconstruction in Strain-Engineered
      (La,Sr)MnO3/LaNiO3 Heterostructures.
AB  - We investigate charge transfer, orbital reconstruction, and the emergence of
      exchange bias in (La,Sr)MnO3/LaNiO3 heterostructures. We demonstrate that charge
      transfer from Mn(3+) ions to Ni(3+) ions is accompanied by the formation of
      hybridized Mn/Ni 3z(2) - r(2) orbits at the interface, instead of strain
      stabilized Mn and Ni x(2) - y(2) orbits in the bulk films. In the
      heterostructures with ultrathin LaNiO3, orbital reconstruction induced by charge
      transfer results in magnetization frustration of (La,Sr)MnO3 at the interface.
      But the strain effect exerted by the growth of the LaNiO3 top layer plays a
      dominant role on orbital reconstruction in the heterostructures with thick
      LaNiO3, stabilizing 3z(2) - r(2) orbits. In this case, robust spin glass,
      associated with larger magnetization frustration, accounts for the exchange bias
      effect. Our work builds a bridge between the microscopic electronic structure and
      the macroscopic magnetic property, providing the possibility of manipulating the
      exotic states with the aid of strain engineering in oxide-based electronics. 

PMID- 26214291
TI  - In this issue September 2015.

PMID- 26214292
TI  - News from the pediatric anesthesia societies: Society for Pediatric Anesthesia
      (SPA).

PMID- 26214293
TI  - Whither dexmedetomidine?
AB  - Dexmedetomidine has established a firm position in the armamentarium of
      anesthesia pharmacology. However, it is still a relatively new drug and its
      application is based on early evidence that is intriguing but far from
      conclusive. Based on experience with previous cure-alls, anesthesia clinicians
      and researchers must insist on more information and formulate appropriate science
      that will allow us to truly understand the role of this dexmedetomidine in our
      specialty-as wonder drug or also-ran.

PMID- 26214294
TI  - How may a mathematical model using ultrasound measurement of antral area be
      predictive of the gastric volume?

PMID- 26214295
TI  - Response to Dr. Phelps et al.: High-dose dexmedetomidine for noninvasive
      pediatric procedural sedation and discharge readiness.

PMID- 26214296
TI  - Correct use of the terms first- and second-generation supraglottic airway
      devices.

PMID- 26214297
TI  - Use of the laryngeal mask airway for pediatric resuscitation.

PMID- 26214298
TI  - Aspiration risk in pyloric stenosis.

PMID- 26214299
TI  - Evaluation of Patients with Community-Acquired Pneumonia Caused by Zoonotic
      Pathogens in an Area with a High Density of Animal Farms.
AB  - Intensive animal farming could potentially lead to outbreaks of infectious
      diseases. Clinicians are at the forefront of detecting unusual diseases, but the
      lack of specificity of zoonotic disease symptoms makes this a challenging task.
      We evaluated patients with community-acquired pneumonia (CAP) with known and
      unknown aetiology in an area with a high livestock density and a potential
      association with animal farms in the proximity. Between 2008 and 2009, a period
      coinciding with a large Q fever outbreak in the Netherlands, patients with CAP
      were tested for the presence of possible respiratory pathogens. The presence and
      number of farm animals within 1 km of the patients' home address were assessed
      using geographic information system (GIS) and were compared between cases and age
      matched control subjects. Of 408 patients with CAP, pathogens were detected in
      275 (67.4%) patients. The presence of sheep and the number of goats were
      associated with CAP caused by Coxiella burnetii in a multiple logistic regression
      model (P < 0.05). CAP with unknown aetiology was not associated with the presence
      of animal farms (P > 0.10). The use of GIS in combination with aetiology of CAP
      could be potentially used to target diagnostics and to identify outbreaks of rare
      zoonotic disease.

PMID- 26214300
TI  - Prevalence of oral Candida in the first year of life.
AB  - Colonisation of the gastrointestinal tract is influenced by primary microbial
      exposure and bioactive factors in breastmilk. The aim was to explore the
      prevalence of oral Candida in the first year of life in relation to selected
      exposures. Oral Candida was studied in 100 healthy infants at 4 and 8 weeks, 3, 6
      and 12 months of age and related to delivery mode, birth weight, infant health
      and feeding, antibiotics, antimycotics, steroids and probiotics in mother and
      infant, living conditions, maternal smoking and infections The association
      between lactoferrin and antisecretory factor in breastmilk and maternal serum
      haemoglobin, transferrin, and ferritin levels in relation to oral Candida was
      also explored. About 11% to 15% of the infants had oral Candida at the respective
      age. Colonisation was fairly stable until 6 months of age. There was no
      conclusive impact of the investigated exposures at entry. Infants with a furry
      pet at home had a lower frequency of Candida at 3 months, (P < 0.05) whereas all
      but one colonised infant had older siblings at 12 months (P < 0.01). Lactoferrin
      in breastmilk was negatively associated with colonisation at 6 months of age. It
      is concluded that 11 to 15% had oral Candida. Exposure to furry pets and siblings
      impacted oral Candida.

PMID- 26214301
TI  - Risk of violence by inmates with childhood trauma and mental health needs.
AB  - Inmates who experienced childhood trauma have higher rates of institutional
      violence. However, the potential intermediate roles of co-occurring mental health
      and substance use needs and early justice involvement have not previously been
      considered. The current study examined the relationships between trauma, mental
      health, substance abuse, youth criminal charges, and institutional violence
      during the first 180 days of incarceration. As secondary aims, we explored
      whether these associations differed by sex or differed for inmates of Aboriginal
      ethnicity. Secondary data from prison records for all 5,154 inmates admitted to a
      federal prison during 2011 were collected. Path analysis was used to estimate the
      direct and indirect associations between trauma and institutional violence.
      Approximately 45% of inmates reported childhood trauma, which was associated with
      a higher prevalence of co-occurring mental health and substance abuse needs, and
      youth criminal charges. Although mental health, substance abuse, and youth
      criminal charges interacted with one another in predicting violence, their
      associations were similar for those with and without histories of trauma. A
      direct association between trauma and institutional incidents remained (Relative
      Risk [RR] = 1.38, 95% CI [1.07, 1.78]) after accounting for indirect associations
      through these co-occurring risk factors. There was insufficient evidence to
      suggest that these associations differed between men and women or between
      Aboriginal and non-Aboriginal inmates. Given the high co-occurrence of multiple
      health and behavioral risk factors for inmates with traumatic histories,
      clarifying which factors are causally associated and reversible is needed to
      inform effective trauma informed care.

PMID- 26214302
TI  - Distinct tubulin dynamics in cancer cells explored using a highly tubulin
      specific fluorescent probe.
AB  - A highly specific fluorescent probe (OC9) was discovered exhibiting tubulin
      specific affinity fluorescence, which allowed selective labeling of cellular
      tubulin in microtubules. Moreover, distinct tubulin dynamics in various cellular
      bio-settings such as drug resistant or epithelial-mesenchymal transition (EMT)
      cancer cells were directly observed for the first time via OC9 staining. 

PMID- 26214303
TI  - African Viper Poly-His Tag Peptide Fragment Efficiently Binds Metal Ions and Is
      Folded into an alpha-Helical Structure.
AB  - Snake venoms are complex mixtures of toxic and often spectacularly biologically
      active components. Some African vipers contain polyhistidine and polyglycine
      peptides, which play a crucial role in the interaction with metal ions during the
      inhibition of snake metalloproteases. Polyhistidine peptide fragments, known as
      poly-His tags, play many important functions, e.g., in metal ion transport in
      bacterial chaperon proteins. In this paper, we report a detailed characterization
      of Cu(2+), Ni(2+), and Zn(2+) complexes with the EDDHHHHHHHHHG peptide fragment
      (pHG) derived from the venom of the rough scale bush viper (Atheris squamigera).
      In order to determine the thermodynamic properties, stoichiometry, binding sites,
      and structures of the metal-pHG complexes, we used a combination of experimental
      techniques (potentiometric titrations, electrospray ionization mass spectrometry,
      UV-vis spectroscopy, circular dichroism spectroscopy, and electron paramagnetic
      resonance spectroscopy) and extensive computational tools (molecular dynamics
      simulations and density functional theory calculations). The results showed that
      pHG has a high affinity toward metal ions. The numerous histidine residues
      located along this sequence are efficient metal ion chelators with high
      affinities toward Cu(2+), Ni(2+), and Zn(2+) ions. The formation of an alpha
      helical structure induced by metal ion coordination and the occurrence of
      polymorphic binding states were observed. It is proposed that metal ions can
      "move along" the poly-His tag, which serves as a metal ion transport pathway. The
      coordination of Cu(2+), Ni(2+), and Zn(2+) ions to the histidine tag is very
      effective in comparison with other histidine-rich peptides. The stabilities of
      the metal-pHG complexes increase in the order Zn(2+) < Ni(2+)? Cu(2+). 

PMID- 26214304
TI  - Personal Continuity of Care in a University-Based Primary Care Practice: Impact
      on Blood Pressure Control.
AB  - Continuity of care is an important quality outcome of patient care. This study
      aimed to investigate the relationship between personal continuity and blood
      pressure (BP) control among the patients with hypertension in an academic primary
      care centre. Between January and May 2012, we conducted a retrospective review of
      medical records of patients with hypertension who had been followed up for at
      least 1 year in the Primary Care Clinic, University of Malaya Medical Centre,
      Malaysia. In this setting, doctors who provided care for hypertension included
      postgraduate family medicine trainees, non-trainee doctors and academic staff.
      Systematic random sampling (1:4) was used for patient selection. BP control was
      defined as less than 130/80 mm Hg for patients with diabetes mellitus,
      proteinuria and chronic kidney disease and less than 140/90 mm Hg for all other
      patients. Continuity of care was assessed using the usual provider continuity
      index (UPCI), which is the ratio of patient visits to the usual provider to the
      total number of visits to all providers in 1 year. A UPC index of zero denotes no
      continuity while an index of one reflects perfect continuity with only the usual
      provider. We reviewed a total of 1060 medical records. The patients' mean age was
      62.0 years (SD 10.4). The majority was women (59.2%) and married (85.7%). The
      mean number of visits in a year was 3.85 (SD 1.36). A total of 72 doctors had
      provided consultations (55 postgraduate family medicine trainees, 8 non-trainee
      doctors and 9 academic staff). The mean UPCI was 0.43 (SD 0.34). Target BP was
      achieved in 42% of the patients. There was no significant relationship between BP
      control and personal continuity after adjustment for total number of visits.
      Continuity of care was not associated with BP control in our centre. Further
      studies are needed to explore the reasons for this. 

PMID- 26214305
TI  - Development of a Targeted Multi-Disorder High-Throughput Sequencing Assay for the
      Effective Identification of Disease-Causing Variants.
AB  - BACKGROUND: While next generation sequencing (NGS) is a useful tool for the
      identification of genetic variants to aid diagnosis and support therapy decision,
      high sequencing costs have limited its application within routine clinical care,
      especially in economically depressed areas. To investigate the utility of a multi
      disease NGS based genetic test, we designed a custom sequencing assay targeting
      over thirty disease-associated areas including cardiac disorders, intellectual
      disabilities, hearing loss, collagenopathies, muscular dystrophy, Ashkenazi
      Jewish genetic disorders, and complex Mendelian disorders. We focused on these
      specific areas based on the interest of our collaborative clinical team,
      suggesting these diseases being the ones in need for the development of a
      sequencing-screening assay. RESULTS: We targeted all coding, untranslated regions
      (UTR) and flanking intronic regions of 650 known disease-associated genes using
      the Roche-NimbleGen EZ SeqCapV3 capture system and sequenced on the Illumina
      HiSeq 2500 Rapid Run platform. Eight controls with known variants and one HapMap
      sample were first sequenced to assess the performance of the panel. Subsequently,
      as a proof of principle and to explore the possible utility of our test, we
      analyzed test disease subjects (n = 16). Eight had known Mendelian disorders and
      eight had complex pediatric diseases. In addition to assess whether copy number
      variation may be of utility as a companion assay relative to these specific
      disease areas, we used the Affymetrix Genome-Wide SNP Array 6.0 to analyze the
      same samples. CONCLUSION: We identified potentially disease-associated variants:
      22 missense, 4 nonsense, 1 frameshift, and 1 splice variants (16 previously
      identified, 12 novel among dbSNP and 15 novel among NHLBI Exome Variant Server).
      We found multi-disease targeted high-throughput sequencing to be a cost efficient
      approach in detecting disease-associated variants to aid diagnosis.

PMID- 26214306
TI  - Comparative Proteomics of Activated THP-1 Cells Infected with Mycobacterium
      tuberculosis Identifies Putative Clearance Biomarkers for Tuberculosis Treatment.
AB  - Biomarkers for determining clearance of Mycobacterium tuberculosis (Mtb)
      infection during anti-tuberculosis therapy or following exposure could facilitate
      enhanced monitoring and treatment. We screened for biomarkers indicating
      clearance of Mtb infection in vitro. A comparative proteomic analysis was
      performed using GeLC MSI/MS. Intracellular and secreted proteomes from activated
      THP-1 cells infected with the Mtb H37Rv strain (MOI = 1) and treated with
      isoniazid and rifampicin for 1 day (infection stage) and 5 days (clearance stage)
      were analyzed. Host proteins associated with early infection (n = 82), clearance
      (n = 121), sustained in both conditions (n = 34) and suppressed by infection (n =
      46) were elucidated. Of the potential clearance markers, SSFA2 and CAECAM18
      showed the highest and lowest protein intensities, respectively. A western blot
      of CAECAM18 validated the LC MS/MS result. For three clearance markers (SSFA2,
      PARP14 and PSME4), in vivo clinical validation was concordantly reported in
      previous patient cohorts. A network analysis revealed that clearance markers were
      enriched amongst four protein interaction networks centered on: (i) CD44/CCND1,
      (ii) IFN-beta1/NF-kappaB, (iii) TP53/TGF-beta and (iv) IFN-gamma/CCL2. After
      infection, proteins associated with proliferation, and recruitment of immune
      cells appeared to be enriched possibly reflecting recruitment of defense
      mechanisms. Counteracting proteins (CASP3 vs. Akt and NF-kappaB vs. TP53)
      associated with apoptosis regulation and its networks were enriched among the
      early and sustained infection biomarkers, indicating host-pathogen competition.
      The BRCA1/2 network was suppressed during infection, suggesting that cell
      proliferation suppression is a feature of Mtb survival. Our study provides
      insights into the mechanisms of host-Mtb interaction by comparing the stages of
      infection clearance. The identified clearance biomarkers may be useful in
      monitoring tuberculosis treatment. 

PMID- 26214307
TI  - Genome-Wide Mapping of 5mC and 5hmC Identified Differentially Modified Genomic
      Regions in Late-Onset Severe Preeclampsia: A Pilot Study.
AB  - Preeclampsia (PE) is a leading cause of perinatal morbidity and mortality.
      However, as a common form of PE, the etiology of late-onset PE is elusive. We
      analyzed 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in the
      placentas of late-onset severe PE patients (n = 4) and normal controls (n = 4)
      using a (hydroxy)methylated DNA immunoprecipitation approach combined with deep
      sequencing ([h]MeDIP-seq), and the results were verified by (h)MeDIP-qPCR. The
      most significant differentially methylated regions (DMRs) were verified by
      MassARRAY EppiTYPER in an enlarged sample size (n = 20). Bioinformatics analysis
      identified 714 peaks of 5mC that were associated with 403 genes and 119 peaks of
      5hmC that were associated with 61 genes, thus showing significant differences
      between the PE patients and the controls (>2-fold, p<0.05). Further, only one
      gene, PTPRN2, had both 5mC and 5hmC changes in patients. The ErbB signaling
      pathway was enriched in those 403 genes that had significantly different 5mC
      level between the groups. This genome-wide mapping of 5mC and 5hmC in late-onset
      severe PE and normal controls demonstrates that both 5mC and 5hmC play epigenetic
      roles in the regulation of the disease, but work independently. We reveal the
      genome-wide mapping of DNA methylation and DNA hydroxymethylation in late-onset
      PE placentas for the first time, and the identified ErbB signaling pathway and
      the gene PTPRN2 may be relevant to the epigenetic pathogenesis of late-onset PE.

PMID- 26214308
TI  - Epigenetic potential of resveratrol and analogs in preclinical models of prostate
      cancer.
AB  - Lifestyle, particularly diet, is a risk factor for prostate cancer. Dietary
      polyphenols such as resveratrol possess anticancer properties and therefore have
      chemopreventive and therapeutic potential. Resveratrol has pleiotropic effects,
      exerting its biological activity through multiple pathways and targets, including
      those associated with cancer. Numerous studies have demonstrated the anticancer
      effects of resveratrol and, to a lesser extent, its analogs, in tissue culture,
      while in vivo observations are limited. Here, we provide a concise summary of our
      results on epigenetic mechanisms of resveratrol and analogs mediated through
      regulation of chromatin modifier metastasis-associated protein 1 (MTA1) and
      microRNAs (miRNAs), and highlight the anticancer effects of these compounds in
      preclinical models of prostate cancer. We suggest that the identified stilbene
      responsive mechanism-based biomarkers, such as MTA1 and oncogenic miRNAs, may
      become indicative of treatment efficacy in prostate cancer. Resveratrol analogs
      with better bioavailability, conferring superior pharmacological potencies and
      greater anticancer effects, may become stronger candidates for clinical
      development. 

PMID- 26214309
TI  - Estimating the Number of Heterosexual Persons in the United States to Calculate
      National Rates of HIV Infection.
AB  - BACKGROUND: This study estimated the proportions and numbers of heterosexuals in
      the United States (U.S.) to calculate rates of heterosexually acquired human
      immunodeficiency virus (HIV) infection. Quantifying the burden of disease can
      inform effective prevention planning and resource allocation. METHODS:
      Heterosexuals were defined as males and females who ever had sex with an opposite
      sex partner and excluded those with other HIV risks: persons who ever injected
      drugs and males who ever had sex with another man. We conducted meta-analysis
      using data from 3 national probability surveys that measured lifetime (ever)
      sexual activity and injection drug use among persons aged 15 years and older to
      estimate the proportion of heterosexuals in the United States population. We then
      applied the proportion of heterosexual persons to census data to produce
      population size estimates. National HIV infection rates among heterosexuals were
      calculated using surveillance data (cases attributable to heterosexual contact)
      in the numerators and the heterosexual population size estimates in the
      denominators. RESULTS: Adult and adolescent heterosexuals comprised an estimated
      86.7% (95% confidence interval: 84.1%-89.3%) of the U.S. population. The estimate
      for males was 84.1% (CI: 81.2%-86.9%) and for females was 89.4% (95% CI: 86.9%
      91.8%). The HIV diagnosis rate for 2013 was 5.2 per 100,000 heterosexuals and the
      rate of persons living with diagnosed HIV infection in 2012 was 104 per 100,000
      heterosexuals aged 13 years or older. Rates of HIV infection were >20 times as
      high among black heterosexuals compared to white heterosexuals, indicating
      considerable disparity. Rates among heterosexual men demonstrated higher
      disparities than overall population rates for men. CONCLUSIONS: The best
      available data must be used to guide decision-making for HIV prevention. HIV
      rates among heterosexuals in the U.S. are important additions to cost
      effectiveness and other data used to make critical decisions about resources for
      prevention of HIV infection.

PMID- 26214310
TI  - DFT study on endohedral and exohedral B38 fullerenes: M@B38 (M = Sc, Y, Ti) and
      M&B38 (M = Nb, Fe, Co, Ni).
AB  - The structures, stabilities and electronic properties of endohedral and exohedral
      B38 fullerenes with transition metal atoms (M = Sc, Y, Ti, Nb, Fe, Co, Ni) are
      studied using all-electron density functional theory. M@B38 (M = Sc, Y, Ti)
      possess endohedral structures as their lowest energy structures, while Nb, Fe, Co
      and Ni atoms favor the coordination of B38 fullerenes in an exohedral manner.
      Sizable HOMO-LUMO gaps and high binding energies imply the viability of M@B38
      towards experimental realization. The distributions of electron density and
      frontier orbitals are analyzed in detail. The analysis of vertical ionization
      potential and vertical electron affinity indicates that M@B38 are good electron
      acceptors and bad electron donors. 

PMID- 26214311
TI  - Identification of Glial Activation Markers by Comparison of Transcriptome Changes
      between Astrocytes and Microglia following Innate Immune Stimulation.
AB  - The activation of astrocytes and microglia is often associated with diseases of
      the central nervous system (CNS). Understanding how activation alters the
      transcriptome of these cells may offer valuable insight regarding how activation
      of these cells mediate neurological damage. Furthermore, identifying common and
      unique pathways of gene expression during activation may provide new insight into
      the distinct roles these cells have in the CNS during infection and inflammation.
      Since recent studies indicate that TLR7 recognizes not only viral RNA but also
      microRNAs that are released by damaged neurons and elevated during neurological
      diseases, we first examined the response of glial cells to TLR7 stimulation using
      microarray analysis. Microglia were found to generate a much stronger response to
      TLR7 activation than astrocytes, both in the number of genes induced as well as
      fold induction. Although the primary pathways induced by both cell types were
      directly linked to immune responses, microglia also induced pathways associated
      with cellular proliferation, while astrocytes did not. Targeted analysis of a
      subset of the upregulated genes identified unique mRNA, including Ifi202b which
      was only upregulated by microglia and was found to be induced during both
      retroviral and bunyavirus infections in the CNS. In addition, other genes
      including Birc3 and Gpr84 as well as two expressed sequences AW112010 and
      BC023105 were found to be induced in both microglia and astrocytes and were
      upregulated in the CNS following virus infection. Thus, expression of these genes
      may a useful measurement of glial activation during insult or injury to the CNS. 

PMID- 26214312
TI  - Effects of a 60 Hz Magnetic Field Exposure Up to 3000 MUT on Human Brain
      Activation as Measured by Functional Magnetic Resonance Imaging.
AB  - Several aspects of the human nervous system and associated motor and cognitive
      processes have been reported to be modulated by extremely low-frequency (ELF, <
      300 Hz) time-varying Magnetic Fields (MF). Due do their worldwide prevalence;
      power-line frequencies (60 Hz in North America) are of particular interest.
      Despite intense research efforts over the last few decades, the potential effects
      of 60 Hz MF still need to be elucidated, and the underlying mechanisms to be
      understood. In this study, we have used functional Magnetic Resonance Imaging
      (fMRI) to characterize potential changes in functional brain activation following
      human exposure to a 60 Hz MF through motor and cognitive tasks. First, pilot
      results acquired in a first set of subjects (N=9) were used to demonstrate the
      technical feasibility of using fMRI to detect subtle changes in functional brain
      activation with 60 Hz MF exposure at 1800 MUT. Second, a full study involving a
      larger cohort of subjects tested brain activation during 1) a finger tapping task
      (N=20), and 2) a mental rotation task (N=21); before and after a one-hour, 60 Hz,
      3000 MUT MF exposure. The results indicate significant changes in task-induced
      functional brain activation as a consequence of MF exposure. However, no impact
      on task performance was found. These results illustrate the potential of using
      fMRI to identify MF-induced changes in functional brain activation, suggesting
      that a one-hour 60 Hz, 3000 MUT MF exposure can modulate activity in specific
      brain regions after the end of the exposure period (i.e., residual effects). We
      discuss the possibility that MF exposure at 60 Hz, 3000 MUT may be capable of
      modulating cortical excitability via a modulation of synaptic plasticity
      processes. 

PMID- 26214313
TI  - Axial Myopia Is Associated with Visual Field Prognosis of Primary Open-Angle
      Glaucoma.
AB  - PURPOSE: To identify whether myopia was associated with the visual field (VF)
      progression of primary open-angle glaucoma (POAG). METHODS: A total of 270 eyes
      of 270 POAG followed up for more than 3 years with >=9 reliable VFs by Octopus
      perimetry were retrospectively reviewed. Myopia was divided into: mild myopia (
      2.99 diopter [D], 0), moderate myopia (-5.99, 3.00 D), marked myopia (-9.00, 
      6.00 D) and non-myopia (0 D or more). An annual change in the mean defect (MD)
      slope >0.22 dB/y and 0.30 dB/y was defined as fast progression, respectively.
      Logistic regression was performed to determine prognostic factors for VF
      progression. RESULTS: For the cutoff threshold at 0.22 dB/y, logistic regression
      showed that vertical cup-to-disk ratio (VCDR; p = 0.004) and the extent of myopia
      (p = 0.002) were statistically significant. When logistic regression was repeated
      after excluding the extent of myopia, axial length (AL; p = 0.008, odds ratio
      [OR] = 0.796) reached significance, as did VCDR (p = 0.001). Compared to eyes
      with AL<=23 mm, the OR values were 0.334 (p = 0.059), 0.309 (p = 0.044), 0.266 (p
      = 0.019), 0.260 (p = 0.018), respectively, for 23 <AL<=24 mm, 24 <AL<=25 mm, 25
      <AL <=26 mm, and AL>26 mm. The significance of vertical cup-to-disk ratio of (p =
      0.004) and the extent of myopia (p = 0.008) did not change for the cutoff
      threshold at 0.30dB/y. CONCLUSIONS: VCDR and myopia were associated with VF
      prognosis of POAG. Axial myopia may be a protective factor against VF
      progression.

PMID- 26214314
TI  - Did alpha-Synuclein and Glucocerebrosidase Coevolve? Implications for Parkinson's
      Disease.
AB  - Mutations in the GBA1 gene are associated with increased risk of Parkinson's
      disease, and the protein produced by the gene, glucocerebrosidase, interacts with
      alpha-synuclein, the protein at the center of the disease etiology. One
      possibility is that the mutations disrupt a beneficial interaction between the
      proteins, and a beneficial interaction would imply that the proteins have
      coevolved. To explore this possibility, a correlated mutation analysis has been
      performed for all 72 vertebrate species where complete sequences of alpha
      synuclein and glucocerebrosidase are known. The most highly correlated pair of
      residue variations is alpha-synuclein A53T and glucocerebrosidase G115E.
      Intriguingly, the A53T mutation is a Parkinson's disease risk factor in humans,
      suggesting the pathology associated with this mutation and interaction with
      glucocerebrosidase might be connected. Correlations with beta-synuclein are also
      evaluated. To assess the impact of lowered species number on accuracy, intra and
      inter-chain correlations are also calculated for hemoglobin, using mutual
      information Z-value and direct coupling analyses. 

PMID- 26214315
TI  - A SURGICAL APPROACH TO LARGE SUBRETINAL HEMORRHAGE USING PARS PLANA VITRECTOMY
      AND 360 degrees  RETINOTOMY.
AB  - PURPOSE: To evaluate the surgical approach of pars plana vitrectomy combined with
      360 degrees  retinotomy and silicon oil tamponade in the treatment of patients
      with large subretinal hemorrhage. METHODS: Prospective, nonrandomized, and
      noncomparative case series study. Consecutive patients with breakthrough vitreous
      hemorrhage and massive subretinal hemorrahge were recruited to have combined
      surgery of pars plana vitrectomy with 360 degrees  retinotomy and silicone oil
      temponade. The main outcomes were best-corrected visual acuity, retina status,
      and postoperative complications. RESULTS: Twenty-one patients (21 eyes) were
      included. The mean follow-up was 19.9 +/- 7.4 months. The mean preoperative
      thickness of subretinal hemorrhage was 4.25 +/- 0.69 mm. All the patients were
      observed to have choroidal neovascularization during the surgical procedure. The
      mean logarithm of the minimum angle of resolution best-corrected visual acuity
      (Snellen equivalent) significantly improved from preoperatively 2.64 (hand
      movement) to 1.73 (7/400), 1.50 (6/200), 1.51 (6/200), and 1.45 (7/200) at 1
      month, 3 months, 6 months after the initial surgery, and final follow-up.
      Postoperative complications included temporary higher intraocular pressure,
      silicone oil emulsification, lens opacification, epimacular membrane, retinal
      pigment epithelium loss, and subretinal fibrosis. At the end of the follow-up,
      retinas were all reattached without any recurrence of choroidal
      neovascularization. CONCLUSION: Pars plana vitrectomy combined with retinotomy
      and silicone oil tamponade is effective for eyes with breakthrough vitreous
      hemorrhage and massive subretinal hemorrahge.

PMID- 26214316
TI  - MP1 AND MAIA FUNDUS PERIMETRY IN HEALTHY SUBJECTS AND PATIENTS AFFECTED BY
      RETINAL DYSTROPHIES.
AB  - PURPOSE: To compare retinal sensitivity obtained with MP1 and MAIA
      microperimeters in patients affected by retinal dystrophies (RD) and in healthy
      subjects. METHODS: Thirty-six patients affected by RD and 25 healthy subjects
      were considered for the study. All patients and controls underwent a complete
      ophthalmic examination including fundus-related perimetry, performed by means of
      two microperimeters, the MP1 (Nidek Technologies) and the MAIA (CenterVue). Main
      outcome of the study was the comparison of retinal sensitivity. Such comparison
      was performed converting the MP1 decibel (dB) values to their MAIA equivalent dB
      values. RESULTS: Mean retinal sensitivity in patients affected by RD was 5.68 +/-
      6.08 dB (mean +/- SD) on MP1 (9.66 +/- 10.06 dB converted to their equivalent
      MAIA values) and 14.66 +/- 9.37 dB on MAIA (P < 0.0001). Mean retinal sensitivity
      in healthy subjects was 18.46 +/- 3.10 dB on MP1 (22.44 +/- 7.08 dB on their
      converted equivalent MAIA values) and 28.52 +/- 1.12 dB on MAIA (P < 0.0001).
      Thirty eyes affected by RD (41%) showed retinal areas characterized by
      sensitivity under 1 dB on MP1, whereas the MAIA examination of the same areas
      revealed a mean retinal sensitivity of 4.7 dB. Moreover, 28 of these eyes
      disclosed also areas of absolute scotoma on MP1, but examining the same areas on
      MAIA, just 13 of these eyes (46%) disclosed an absolute scotoma. In addition, in
      a subgroup of 6 eyes affected by RD (8%) showing a retinal sensitivity of 20 dB
      on MP1, the corresponding value on MAIA varied from 26.3 dB to 30.0 dB, with a
      mean value of 27.8 +/- 1.3 dB. CONCLUSION: The MAIA microperimeter provides a
      more accurate characterization of functional impairment in RD with respect to the
      MP1 system, especially in cases with low and high retinal sensitivity. MAIA
      microperimeter could reveal particularly useful in precisely identifying and
      monitoring subtle changes in retinal sensitivity, especially in view of the
      availability of therapies aiming at a functional rescue in patients with RD.

PMID- 26214317
TI  - Nanomaterial-based activatable imaging probes: from design to biological
      applications.
AB  - Activatable imaging probes as alternatives to "always on" imaging probes have
      attracted more and more attention due to their improved sensitivity and
      specificity. They are commonly designed to amplify or boost imaging signals only
      in response to specific biomolecular recognition or interaction. Thus, the design
      strategies play a vital role in the fabrication of activatable imaging probes. In
      this review, we focus on the design mechanisms and biological applications of
      those nanomaterial-based activatable imaging probes reported in the past five
      years, benefitting greatly from the good development of nanotechnology. These
      probes not only include the most studied activatable fluorescence imaging probes,
      but also cover more activatable MR imaging probes based on nanoparticle contrast
      agents and activatable photoacoustic imaging probes, providing more bases for
      clinical translation. 

PMID- 26214318
TI  - The Impact of Socioeconomic Status on the Utilization of Spinal Imaging.
AB  - BACKGROUND: Few studies have examined the general correlation between
      socioeconomic status and imaging. This study is the first to analyze this
      relationship in the spine patient population. OBJECTIVE: To assess the effect of
      socioeconomic status on the frequency with which imaging studies of the lumbar
      spine are ordered and completed. METHODS: Patients that were diagnosed with
      lumbar radiculopathy and/or myelopathy and had at least 1 subsequent lumbar
      magnetic resonance imaging (MRI), computed tomography (CT), or X-ray ordered were
      retrospectively identified. Demographic information and the number of ordered and
      completed imaging studies were among the data collected. Patient insurance status
      and income level (estimated based on zip code) served as representations of
      socioeconomic status. RESULTS: A total of 24,105 patients met the inclusion
      criteria for this study. Regression analyses demonstrated that uninsured patients
      were significantly less likely to have an MRI, CT, or X-ray study ordered (P <
      .001 for all modalities) and completed (P < .001 for MRI and X-ray, P = .03 for
      CT). Patients with lower income had higher rates of MRI, CT, and X-ray (P < .001
      for all) imaging ordered but were less likely to have an ordered X-ray be
      completed (P = .009). There was no significant difference in the completion rate
      of ordered MRIs or CTs. CONCLUSION: Disparities in image utilization based on
      socioeconomic characteristics such as insurance status and income level highlight
      a critical gap in access to health care. Physicians should work to mitigate the
      influence of such factors when deciding whether to order imaging studies,
      especially in light of the ongoing shift in health policy in the United States.

PMID- 26214319
TI  - Repeat Radiosurgery for Trigeminal Neuralgia.
AB  - BACKGROUND: Repeat Gamma Knife radiosurgery (GKRS) is an established option for
      patients whose pain has recurred after the initial procedure, with reported
      success rates varying from 68% to 95%. Predictive factors for response to the
      repeat GKRS are ill-defined. OBJECTIVE: This cohort study aimed to report the
      outcomes and factors predictive of success for patients who have undergone
      repeated GKRS for trigeminal neuralgia at Wake Forest University Baptist Medical
      Center. METHODS: Between 1999 and 2013, 152 patients underwent repeat GKRS at
      Wake Forest, 125 of whom were available for long-term follow-up. A retrospective
      chart review and telephone interviews were conducted to determine background
      medical history, dosimetric data, outcomes, and adverse effects of the procedure.
      RESULTS: Eighty-four percent of patients achieved at least Barrow Neurological
      Institute (BNI) IIIb pain relief, with 46% achieving BNI I. The 1-, 3-, and 5
      year rates of BNI I pain relief were 63%, 50%, and 37%, respectively. The 1-, 3-,
      and 5-year rates of BNI IIIb or better pain relief were 74%, 59%, and 46%,
      respectively. One patient experienced bothersome numbness and 2 patients
      developed anesthesia dolorosa. The dominant predictive factors for pain relief
      were facial numbness after the first GKRS and a positive pain response to the
      first GKRS. CONCLUSION: Repeat GKRS is an effective method of treating recurrent
      trigeminal neuralgia. Patients who have facial numbness after the first treatment
      and a positive pain response to the first GKRS are significantly more likely to
      respond well to the second treatment.

PMID- 26214320
TI  - Surgical Outcomes for Minimally Invasive vs Open Transforaminal Lumbar Interbody
      Fusion: An Updated Systematic Review and Meta-analysis.
AB  - BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (TLIF)-or
      MI-TLIF-has been increasing in prevalence compared with open TLIF (O-TLIF)
      procedures. The use of MI-TLIF is an evolving technique with conflicting reports
      in the literature about outcomes. OBJECTIVE: To investigate the impact of MI-TLIF
      in comparison with O-TLIF for early and late outcomes by using the Visual Analog
      Scale for back pain (VAS-back) and the Oswestry Disability Index (ODI). Secondary
      end points include blood loss, operative time, radiation exposure, length of
      stay, fusion rates, and complications between the 2 procedures. METHODS: During
      August 2014, a systematic literature search was performed identifying 987
      articles. Of these, 30 met inclusion criteria. A random-effects meta-analysis was
      performed by using both pooled and subset analyses based on study type. RESULTS:
      Our meta-analysis demonstrated that MI-TLIF reduced blood loss (P < .001), length
      of stay (P < .001), and complications (P = .001) but increased radiation exposure
      (P < .001). No differences were found in fusion rate (P = .61) and operative time
      (P = .34). A decrease in late VAS-back scores was demonstrated for MI TLIF (P <
      .001), but no differences were found in early VAS-back, early ODI, and late ODI.
      CONCLUSION: MI-TLIF is associated with reduced blood loss, decreased length of
      stay, decreased complication rates, and increased radiation exposure. The rates
      of fusion and operative time are similar between MI-TLIF and O-TLIF. Differences
      in long-term outcomes in MI-TLIF vs O-TLIF are inconclusive and require more
      research, particularly in the form of large, multi-institutional prospective
      randomized controlled trials. ABBREVIATIONS: CI, confidence intervalMCID, minimal
      clinically important differenceMI-TLIF, minimally invasive transforaminal lumbar
      interbody fusionODI, Oswestry Disability IndexO-TLIF, open transforaminal lumbar
      interbody fusionVAS, Visual Analog Scale.

PMID- 26214321
TI  - Carvacrol inhibits proliferation and induces apoptosis in human colon cancer
      cells.
AB  - Colon cancer is one of the most common malignancies worldwide and has a high
      mortality rate. Carvacrol is a major component of oregano and thyme essential
      oils and shows antitumor properties. Here, we investigated the effects of
      carvacrol on the proliferation and apoptosis of two human colon cancer cell
      lines, HCT116 and LoVo, and studied the molecular mechanisms of its antitumor
      properties. We found that carvacrol inhibited the proliferation and migration of
      the two colon cancer cell lines in a concentration-dependent manner. Cell
      invasion was suppressed after carvacrol treatment by decreasing the expression of
      matrix metalloprotease-2 (MMP-2) and MMP-9. Carvacrol treatment also caused cell
      cycle arrest in the G2/M phase and decreased cyclin B1 expression. Finally,
      carvacrol induced cell apoptosis in a dose-dependent manner. At the molecular
      level, carvacrol downregulated the expression of Bcl-2 and induced the
      phosphorylation of the extracellular-regulated protein kinase and protein kinase
      B (p-Akt). In parallel, carvacrol upregulated the expression of Bax and c-Jun N
      terminal kinase. These results indicate that carvacrol might induce apoptosis in
      colon cancer cells through the mitochondrial apoptotic pathway and the MAPK and
      PI3K/Akt signaling pathways. Together, our results suggest that carvacrol may
      have therapeutic potential for the prevention and treatment of colon cancer. 

PMID- 26214322
TI  - The impact of computer use on therapeutic alliance and continuance in care during
      the mental health intake.
AB  - Advances in information technology within clinical practice have rapidly expanded
      over recent years. Despite the documented benefits of using electronic health
      records, which often necessitate computer use during the clinical encounter,
      little is known about the impact of computer use during the mental health visit
      and its effect on the quality of the therapeutic alliance. We investigated the
      association between computer use and quality of the working alliance and
      continuance in care in 104 naturalistic mental health intake sessions. Data were
      collected from 8 safety-net outpatient clinics in the Northeast offering mental
      health services to a diverse client population. All intakes were video recorded.
      Use of computer during the intake session was ascertained directly from the
      recording of the session (n = 22; 22.15% of intakes). Working alliance was
      assessed from the session videotapes by independent reliable coders, using the
      Working Alliance Inventory, Observer Form-bond scale. Therapist computer use was
      significantly associated with the quality of the observer-rated therapeutic
      alliance (Coefficient = -6.29, SE = 2.2, p < .01; Cohen's effect size of d = 
      0.76), and client's continuance in care (Odds ratio = .11, CI = 0.03-0.38; p <
      .001). The quality of the observer-rated working alliance and client's
      continuance in care were significantly lower in intakes in which the therapist
      used a computer during the session. Findings indicate a cautionary call in
      advancing computer use within the mental health intake, and demonstrate the need
      for future research to identify the specific behaviors that promote or hinder a
      strong working alliance within the context of psychotherapy in the technological
      era.

PMID- 26214323
TI  - Streamlining the OncoScan(r) Array Procedure for Use in a Clinical Laboratory.
AB  - Microarray analysis has found tremendous utility in the clinical laboratory
      testing for detection of copy number changes (CNCs) and loss of heterozygosity
      (LOH). Recently the OncoScan(r) array was introduced as a tool for identification
      of CNCs and LOH in formalin-fixed paraffin-embedded oncology samples. The
      objective of this study was to identify steps in the OncoScan procedure that
      could be modified to make the process more efficient and technician-friendly in
      the clinical laboratory setting. Eighteen samples previously processed according
      to the manufacturer-recommended protocol were reprocessed using a modified
      protocol. The two primary modifications to the protocol included the elimination
      of a brief "chill and spin" step and an adjustment to the overnight hybridization
      temperature to allow for simultaneous hybridization of OncoScan and CytoScan(r)
      arrays. A comparison of paired samples processed using both protocols showed that
      our modified protocol performs similarly to the manufacturer-recommended
      protocol, yielding equivalent quality control metrics and calls. 

PMID- 26214324
TI  - The Influence of Sex and Laterality on Clubfoot Severity.
AB  - BACKGROUND: Idiopathic clubfoot is bilateral in approximately 50% of cases and
      has been widely reported to affect males more frequently than females. Despite
      these observations, the correlation between sex and severity of the deformity has
      not been established. As well, the difference in severity between unilateral and
      bilateral clubfeet has not been extensively investigated. Therefore, the goals of
      the present study were to: (1) examine the relationship between sex and severity
      of deformity and (2) determine the relationship between laterality and severity
      of deformity. METHODS: The families of infants with idiopathic clubfoot deformity
      treated at our institution were prospectively invited to participate in this
      institutional review board-approved study. Severity of the deformity was assessed
      by a single surgeon for each patient using the Dimeglio criteria at the first
      clinic visit. After evaluating the distributions, the correlations were
      quantified by nonparametric analyses. RESULTS: Over 8 years, 240 infants met the
      inclusion criteria. There was no significant difference in the severity of
      deformity due to sex (P=0.61): the median Dimeglio score for males was 13
      (variance 4.8) and for females, the median was 13.0 (variance of 5.1). In
      contrast, severity was distributed differently among unilateral versus bilateral
      patients. Although both unilateral and bilateral patients had a median Dimeglio
      score of 13, the ratio of bilateral patients was higher among those with moderate
      or very severe deformities compared with those with severe deformities (P<0.01).
      CONCLUSIONS: Although idiopathic clubfoot is commonly considered to affect male
      patients disproportionately, this is the first study to document no difference in
      severity due to sex. Further, this study demonstrated that on average, bilateral
      patients did not have increased severity, but presented with a larger range of
      severity than those patients with unilateral deformity. LEVEL OF EVIDENCE: Level
      III-prognostic.

PMID- 26214325
TI  - Femoral Version and Tibial Torsion are Not Associated With Hip or Knee Arthritis
      in a Large Osteological Collection.
AB  - BACKGROUND: Tibial torsion and femoral anteversion are common rotational
      abnormalities in children, and their courses are most often benign and self
      resolving. Although neither usually requires surgical treatment, the decision to
      perform a derotational osteotomy is usually based on the degree of functional
      impairment. Neither condition is thought to influence the development of
      osteoarthritis of the hip or knee; however, to date there have been no large
      scale studies confirming this. METHODS: Tibial torsion and femoral version in
      1158 cadaveric tibiae and femora were measured using a camera setup based on
      previously described radiographic landmarks. Any specimens with obvious
      traumatic, rheumatic, or metabolic abnormalities were excluded. Degenerative
      joint disease of the hip and knee were each graded from 0 to 6. Correlations
      between tibial torsion, femoral version, age, race, and sex with osteoarthritis
      of the hip and knee joints were evaluated with multiple regression analysis.
      RESULTS: The mean and SDs of tibial torsion and femoral anteversion were 7.9+/
      8.8 and 11.4+/-12.0 degrees, respectively. African Americans had significantly
      increased tibial torsion (5.1+/-8.7 vs. 9.2+/-8.5 degrees, P<0.0005) and greater
      femoral anteversion (14.1+/-11.9 vs. 10.2+/-11.8 degrees, P<0.0005) compared with
      whites. The average grades for hip and knee osteoarthritis were 3.1+/-1.4 and
      2.7+/-1.4. Using multiple regression analysis neither tibial torsion nor femoral
      version were independent predictors of hip or knee arthritis (P>0.05 for all).
      DISCUSSION: This study confirmed previously reported differences in the
      rotational profiles between races and sexes. However, neither tibial torsion nor
      femoral anteversion had a significant influence on the development of arthritis
      of the hip or knee. CLINICAL RELEVANCE: These results support the practice of
      treating tibial torsion and femoral anteversion based on the symptomatology of
      the patient. Parents of asymptomatic children can be reassured that long-term
      consequences are unlikely.

PMID- 26214326
TI  - Wound Closure in Nonidiopathic Scoliosis: Does Closure Matter?
AB  - BACKGROUND: Postoperative wound complications after posterior spinal fusion are
      difficult to manage. The incidence in the nonidiopathic patient population is
      significantly higher than the adolescent idiopathic population. A comparison of
      wound complications after posterior spinal fusion for nonidiopathic scoliosis
      between the utilization of the orthopaedic surgical team at the time of closure
      performing a nonstandardized wound closure versus a plastic surgeon with a
      plastic multilayered closure technique and rotational flap coverage when needed
      had not previously been evaluated. The purpose of this study was to compare the
      complication rate between nonstandardized and plastic multilayered closure of the
      surgical incision in patients undergoing posterior spinal fusion for
      nonidiopathic scoliosis. METHODS: The charts of 76 patients with a primary
      diagnosis of scoliosis associated with a syndrome or neuromuscular disease and
      who underwent a posterior spinal fusion were reviewed. Forty-two patients had
      their incisions closed using the nonstandardized technique and 34 using the
      plastic multilayered technique. These 2 groups were compared for age, sex,
      primary diagnosis, number of levels fused, estimated blood loss, number of units
      transfused, operating room time, wound complication, and return to operating
      room. RESULTS: The wound complication rate in the nonstandardized closure group
      was 19% (8/42) compared with 0% (0/34) in the plastic multilayered closure group
      (P=0.007). The unanticipated return to the operating room rate was 11.9% (5/42)
      for the nonstandardized closure patients versus 0% (0/34) for the plastic
      multilayered closure patients (P=0.061). CONCLUSIONS: The use of the plastic
      multilayered closure technique in this patient population is important in an
      effort to decrease postoperative wound complications. The ability of the surgical
      team to decrease the infection rate of nonidiopathic scoliosis cannot be
      overstated. The method of wound closure plays a major role in lowering this
      incidence. LEVEL OF EVIDENCE: Level III-therapeutic.

PMID- 26214327
TI  - Use of a Novel Pathway for Early Discharge Was Associated With a 48% Shorter
      Length of Stay After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.
AB  - INTRODUCTION: Hospital stay after posterior spinal fusion (PSF) for adolescent
      idiopathic scoliosis (AIS) has decreased only modestly over time despite a
      healthy patient population. The purpose of this study was to evaluate the impact
      of a novel postoperative pathway on length of stay (LOS) and complications.
      METHODS: A retrospective review of patients undergoing PSF for AIS in 2011 to
      2012 was performed at 2 institutions evaluating demographics, preoperative Cobb
      angles, surgical duration, blood loss, LOS, and postoperative complications.
      Patients at one center were managed using an accelerated discharge (AD) pathway
      emphasizing early transition to oral pain medications mobilization with physical
      therapy 2 to 3 times/d, and discharge regardless of return of bowel function.
      Expectations were set with the family before surgery for early discharge.
      Patients at the other center were managed without a standardized pathway.
      RESULTS: One hundred five patients underwent PSF and were treated by an AD
      pathway, whereas 45 patients were managed using a traditional discharge (TD)
      pathway. There was no difference in proximal thoracic and main thoracic Cobb
      magnitudes and a small difference in thoracolumbar curve magnitudes (35.2+/-13.0
      degrees AD vs. 40.6+/-11.4 degrees TD, P=0.004) between groups. Surgical time was
      slightly shorter in AD patients (median 3.1 vs. 3.9 h, P=0.0003) with no
      difference in estimated blood loss. LOS was 48% shorter in the AD group (2.2 vs.
      4.2 d, P<0.0001). There was no difference in readmissions or wound complications
      between groups. CONCLUSIONS: Hospital stay was nearly 50% shorter in patients
      managed by the AD pathway without any increase in readmissions or early
      complications. SIGNIFICANCE: Discharge after PSF for AIS may be expedited using a
      coordinated postoperative pathway. No increase in complications was seen using
      the AD pathway. Earlier discharge may reduce health care costs and allow an
      earlier return to normalcy for families. LEVEL OF EVIDENCE: Level III-case
      control study.

PMID- 26214328
TI  - Ankle Range of Motion After Posterior Subtalar and Ankle Capsulotomy for Relapsed
      Equinus in Idiopathic Clubfoot.
AB  - INTRODUCTION: Posterior capsulotomy can correct residual clubfoot deformity, but
      has been associated with ankle stiffness. The purpose of this study was to
      evaluate clinical ankle range of motion (ROM) following posterior capsulotomy
      immediately postsurgery and during long-term follow-up. METHODS: A retrospective
      clinical and radiographic review of 257 patients (398 feet) was performed to
      evaluate all patients who required a posterior capsulotomy as part of their
      clubfoot management. Twenty feet (16 patients) were identified with a mean age of
      73.3+/-37.7 months and mean Pirani score of 5.2+/-0.8 points. Following
      capsulotomy, a long-leg cast was placed and maintained for a mean of 26 days
      (range, 21 to 35 d). At cast removal, parents were trained and instructed to
      immediately begin home physiotherapy. The capsulotomy cohort was age and sex
      matched to a cohort treated exclusively with the Ponseti method for comparison.
      Children in the comparison cohort had a mean Pirani score of 5.7+/-0.8 points.
      RESULTS: The mean dorsiflexion in the capsulotomy cohort significantly increased
      comparing the preoperative to the immediate postoperative ROM (from -6.5 to +9.7
      degrees). No significant reduction in this gain was observed at latest follow-up
      (to +8.3 degrees). No significant difference in the plantar-flexion angle was
      found. Radiographically, a significant improvement in the lateral anterior tibial
      calcaneal angle angles was found (P<0.05). CONCLUSIONS: If utilizing our protocol
      for early mobilization, limited use of capsulotomy to treat relapsed clubfoot
      does not necessarily reduce ankle ROM. Our protocol of placing the feet in casts
      for a shorter duration of time and providing early physiotherapy helps maintain
      ankle ROM after a posterior capsulotomy. LEVEL OF EVIDENCE: Level III-therapeutic
      study.

PMID- 26214329
TI  - Percutaneous Subtrochanteric Osteotomy for Painful Dislocated Hips in Patients
      With Cerebral Palsy.
AB  - BACKGROUND: Treatment of a painful, chronically dislocated hip in nonambulatory
      children with cerebral palsy (CP) is challenging and controversial. Although many
      surgical options have been described, there is limited information, including
      patient-centered outcomes, following treatment. The purpose of our study was to
      evaluate the effect of a percutaneous subtrochanteric valgus osteotomy (SVO)
      using external fixation (EF) on hip abduction, radiographic parameters, and
      quality of life (QOL) measures in such patients. METHODS: Fifteen nonambulatory
      patients (8 male, 7 female) with CP with 19 chronically dislocated hips underwent
      SVO using EF and adductor tenotomy at an average age of 14.3 years (range, 10.7
      to 26.8 y). Changes in hip abduction and radiographic angular correction
      following surgery were assessed. Caregivers completed 2 surveys detailing
      differences in the patient's QOL measures, including severity and duration of
      pain and ease of nursing care, and the modified Child Health Index of Life with
      Disabilities (CPCHILD). RESULTS: Caregivers of 11 patients completed both surveys
      at an average follow-up of 50 months (range, 17 to 119 mo) after fixator removal.
      There was improvement in pain, sitting tolerance, ease of transfers, and perineal
      care in the majority (9/11) of patients. The modified CPCHILD (possible score, 10
      to 50) improved from 27.2 to 16.23 (P=0.05). Hip abduction improved from -7
      degrees (range, -32 to 5 degrees) to 24 degrees (range, 0 to 40 degrees)
      (P<0.0001). The average valgus osteotomy correction was 48.2 degrees (range, 2.2
      to 93.2 degrees). The pelvic femoral shaft angle improved from -15.2 degrees
      (range, -47.7 to 7.4 degrees) to 15.4 degrees (-44.3 to 44.6 degrees). There was
      some correlation of both, change in hip abduction (R=0.55) and osteotomy angle
      (R=0.60), with improvement in QOL measures. There were 3 major complications
      (20%) in 15 patients. CONCLUSIONS: On the basis of preliminary results,
      percutaneous SVO stabilized with EF improves QOL in the majority of nonambulatory
      CP patients despite untoward events and is a viable alternative to open osteotomy
      with internal fixation. More robust comparative studies are needed to further
      assess the optimal salvage technique in this patient population. LEVEL OF
      EVIDENCE: Level IV.

PMID- 26214330
TI  - The Conclusions Reached by MJ Heffernan et al, May be Incorrect (MJ Heffernan et
      al, "Treatment of Femur Fractures in Young Children: A Multicenter Comparison of
      Flexible Intramedullary Nails to Spica Casting in Young Children Aged 2 to 6
      Years").

PMID- 26214331
TI  - Letter to the Editor Regarding: "Two Cases of Avascular Necrosis After
      Prophylactic Pinning of the Asymptomatic, Contralateral Femoral Head for Slipped
      Capital Femoral Epiphysis: Case Report and Review of the Literature".

PMID- 26214332
TI  - The current status of molecular diagnosis of inherited retinal dystrophies.
AB  - PURPOSE OF REVIEW: We are witnessing lightning-fast advances in the molecular
      diagnosis of inherited retinal dystrophies, mainly due to the widespread use of
      next-generation sequencing technologies. The purpose of this review is to
      highlight the breadth of findings from this in-depth testing approach, and to
      propose changes to our traditional testing and diagnostic paradigms. Lessons
      learned from modern molecular testing suggest that the previous concept of
      inherited retinal dystrophies as a group of 'single gene diseases' may require a
      significant update. RECENT FINDINGS: All of the known retinal dystrophies genes
      can now be sequenced. In many cases, this nonhypothesis driven testing strategy
      is uncovering mutations in unsuspected genes, generating data that challenges
      established concepts of genetic mechanisms and provides insights regarding genes
      previously thought to be exclusively related to syndromic disease. Recent
      advances in testing have improved not only the breadth, but also the depth of
      genetic data. For example, deep intronic sequencing has uncovered many novel
      intronic mutations/variations in the ABCA4 gene. SUMMARY: Currently, in
      approximately 50-60% of patients with nonsyndromic retinal dystrophy, the disease
      mechanism can be identified. The presence of pathogenic alleles in more than one
      gene is not uncommon. Retinal dystrophy, with relatively defined clinical
      presentations and a large but limited number of genes involved, is becoming a
      model for the next-generation study of molecular disease mechanisms.

PMID- 26214333
TI  - To Be or Not to Be: Bayesian Correction for Misclassification of Self-reported
      Sexual Behaviors Among Men Who Have Sex with Men.
AB  - BACKGROUND: Inferring sexual behavior of a stigmatized minority through self
      reported sexual identity is subject to misclassification and can lead to biased
      results. We quantify the degree of this misclassification and perform a Bayesian
      correction of the risk of HIV infection in relation to self-reported sexual
      behavior. METHODS: Sensitivity and specificity of self-reported men who have sex
      with men in ascertaining sexual behavior was derived from validation data, as was
      the informative prior on the association of same-sex behavior with self-reported
      HIV infection. Using these priors, we performed two separate Bayesian analyses of
      National Epidemiologic Survey on Alcohol and Related Conditions data for the odds
      of self-reported HIV positivity, adjusting for differential misclassification of
      self-reported same-sex behavior indicated by either partner gender or sexual
      identity. RESULTS: We found differential exposure misclassification with
      specificity exceeding sensitivity, and higher misclassification rates based on
      sexual identity compared with partner gender. Sexual identity and partner gender
      displayed different associations with HIV infection in the raw data but these
      became virtually identical when adjusted for estimates of misclassification of
      sexual behavior by these two indicators. The estimate of prevalence of same-sex
      behavior associated with an elevated risk of HIV infection decreased after
      adjustment for misclassification. CONCLUSIONS: Studies of risk due to same-sex
      behavior are likely biased when they rely on self-identification for
      ascertainment of risk factors, especially when self-reported identity is used.
      The implications of our findings on risk modeling cannot be assumed to be trivial
      due to substantial shifts in distributions of risk and prevalence of exposure.

PMID- 26214335
TI  - Commentary: Breaking Bias: Improved Methods for Analyzing HIV/AIDS Data.

PMID- 26214334
TI  - Estimating HIV Incidence, Time to Diagnosis, and the Undiagnosed HIV Epidemic
      Using Routine Surveillance Data.
AB  - BACKGROUND: Estimates of the size of the undiagnosed HIV-infected population are
      important to understand the HIV epidemic and to plan interventions, including
      "test-and-treat" strategies. METHODS: We developed a multi-state back-calculation
      model to estimate HIV incidence, time between infection and diagnosis, and the
      undiagnosed population by CD4 count strata, using surveillance data on new HIV
      and AIDS diagnoses. The HIV incidence curve was modelled using cubic splines. The
      model was tested on simulated data and applied to surveillance data on men who
      have sex with men in The Netherlands. RESULTS: The number of HIV infections could
      be estimated accurately using simulated data, with most values within the 95%
      confidence intervals of model predictions. When applying the model to Dutch
      surveillance data, 15,400 (95% confidence interval [CI] = 15,000, 16,000) men who
      have sex with men were estimated to have been infected between 1980 and 2011. HIV
      incidence showed a bimodal distribution, with peaks around 1985 and 2005 and a
      decline in recent years. Mean time to diagnosis was 6.1 (95% CI = 5.8, 6.4) years
      between 1984 and 1995 and decreased to 2.6 (2.3, 3.0) years in 2011. By the end
      of 2011, 11,500 (11,000, 12,000) men who have sex with men in The Netherlands
      were estimated to be living with HIV, of whom 1,750 (1,450, 2,200) were still
      undiagnosed. Of the undiagnosed men who have sex with men, 29% (22, 37) were
      infected for less than 1 year, and 16% (13, 20) for more than 5 years.
      CONCLUSIONS: This multi-state back-calculation model will be useful to estimate
      HIV incidence, time to diagnosis, and the undiagnosed HIV epidemic based on
      routine surveillance data.

PMID- 26214336
TI  - Simultaneous Treatment of Missing Data and Measurement Error in HIV Research
      Using Multiple Overimputation.
AB  - BACKGROUND: Both CD4 count and viral load in HIV-infected persons are measured
      with error. There is no clear guidance on how to deal with this measurement error
      in the presence of missing data. METHODS: We used multiple overimputation, a
      method recently developed in the political sciences, to account for both
      measurement error and missing data in CD4 count and viral load measurements from
      four South African cohorts of a Southern African HIV cohort collaboration. Our
      knowledge about the measurement error of ln CD4 and log10 viral load is part of
      an imputation model that imputes both missing and mismeasured data. In an
      illustrative example, we estimate the association of CD4 count and viral load
      with the hazard of death among patients on highly active antiretroviral therapy
      by means of a Cox model. Simulation studies evaluate the extent to which multiple
      overimputation is able to reduce bias in survival analyses. RESULTS: Multiple
      overimputation emphasizes more strongly the influence of having high baseline CD4
      counts compared to both a complete case analysis and multiple imputation (hazard
      ratio for >200 cells/mm vs. <25 cells/mm: 0.21 [95% confidence interval: 0.18,
      0.24] vs. 0.38 [0.29, 0.48], and 0.29 [0.25, 0.34], respectively). Similar
      results are obtained when varying assumptions about measurement error, when using
      p-splines, and when evaluating time-updated CD4 count in a longitudinal analysis.
      The estimates of the association with viral load are slightly more attenuated
      when using multiple imputation instead of multiple overimputation. Our simulation
      studies suggest that multiple overimputation is able to reduce bias and mean
      squared error in survival analyses. CONCLUSIONS: Multiple overimputation, which
      can be used with existing software, offers a convenient approach to account for
      both missing and mismeasured data in HIV research.

PMID- 26214337
TI  - Brief Report: Respondent-driven Sampling Estimators Under Real and Theoretical
      Recruitment Conditions of Female Sex Workers in China.
AB  - We compare the performance of multiple respondent-driven sampling estimators
      under different sample recruitment conditions in hidden populations of female sex
      workers in the midst of China's ongoing epidemic of sexually transmitted
      infections. We first examine empirically calibrated simulations grounded in
      survey data to evaluate the relative performance of each estimator under ideal
      sampling conditions consistent with respondent-driven sampling assumptions and
      under conditions that mimic observed respondent-driven sampling recruitment
      processes. One estimator, which incorporates respondents' reports on their
      network of contacts, substantially out-performs the others under all conditions.
      We then apply the estimators to empirical samples of female sex workers collected
      in two Chinese cities that include unique data on respondents' networks. These
      empirical results are consistent with the simulation results, suggesting that
      traditional respondent-driven sampling estimators overestimate the proportion of
      female sex workers working in low tiers of sex work and are likely to overstate
      the sexually transmitted infection risk profiles of these populations. 

PMID- 26214338
TI  - Multiple Imputation to Account for Measurement Error in Marginal Structural
      Models.
AB  - BACKGROUND: Marginal structural models are an important tool for observational
      studies. These models typically assume that variables are measured without error.
      We describe a method to account for differential and nondifferential measurement
      error in a marginal structural model. METHODS: We illustrate the method
      estimating the joint effects of antiretroviral therapy initiation and current
      smoking on all-cause mortality in a United States cohort of 12,290 patients with
      HIV followed for up to 5 years between 1998 and 2011. Smoking status was likely
      measured with error, but a subset of 3,686 patients who reported smoking status
      on separate questionnaires composed an internal validation subgroup. We compared
      a standard joint marginal structural model fit using inverse probability weights
      to a model that also accounted for misclassification of smoking status using
      multiple imputation. RESULTS: In the standard analysis, current smoking was not
      associated with increased risk of mortality. After accounting for
      misclassification, current smoking without therapy was associated with increased
      mortality (hazard ratio [HR]: 1.2 [95% confidence interval [CI] = 0.6, 2.3]). The
      HR for current smoking and therapy [0.4 (95% CI = 0.2, 0.7)] was similar to the
      HR for no smoking and therapy (0.4; 95% CI = 0.2, 0.6). CONCLUSIONS: Multiple
      imputation can be used to account for measurement error in concert with methods
      for causal inference to strengthen results from observational studies.

PMID- 26214339
TI  - Comparison of spatial filters and features for the detection and classification
      of movement-related cortical potentials in healthy individuals and stroke
      patients.
AB  - OBJECTIVE: The possibility of detecting movement-related cortical potentials
      (MRCPs) at the single trial level has been explored for closing the motor control
      loop with brain-computer interfaces (BCIs) for neurorehabilitation. A distinct
      feature of MRCPs is that the movement kinetic information is encoded in the brain
      potential prior to the onset of the movement, which makes it possible to timely
      drive external devices to provide sensory feedback according to the efferent
      activity from the brain. The aim of this study was to compare methods for the
      detection (different spatial filters) and classification (features extracted from
      various domains) of MRCPs from continuous electroencephalography recordings from
      executed and imagined movements from healthy subjects (n = 24) and attempted
      movements from stroke patients (n = 6) to optimize the performance of MRCP-based
      BCIs for neurorehabilitation. APPROACH: The MRCPs from four cue-based tasks were
      detected with a template matching approach and a set of spatial filters, and
      classified with a linear support vector machine using the combination of
      temporal, spectral, time-scale, or entropy-based features. MAIN RESULTS: The best
      spatial filter (large Laplacian spatial filter (LLSF)) resulted in a true
      positive rate of 82 +/- 9%, 78 +/- 12% and 72 +/- 9% (with detections occurring ~
      200 ms before the onset of the movement) for executed, imagined and attempted
      movements (stroke patients). The best feature combination (temporal and spectral)
      led to pairwise classification of 73 +/- 9%, 64 +/- 10% and 80 +/- 12%. When the
      detection was combined with classification, 60 +/- 10%, 49 +/- 10% and 58 +/- 10%
      of the movements were both correctly detected and classified for executed,
      imagined and attempted movements. A similar performance for detection and
      classification was obtained with optimized spatial filtering. SIGNIFICANCE: A
      simple setup with an LLSF is useful for detecting cued movements while the
      combination of features from the time and frequency domain can optimize the
      decoding of kinetic information from MRCPs; this may be used in neuromodulatory
      BCIs.

PMID- 26214340
TI  - A Flexible Microporous Hydrogen-Bonded Organic Framework for Gas Sorption and
      Separation.
AB  - A microporous three-dimensional hydrogen-bonded organic framework (HOF-5) has
      been constructed from a new organic linker 4,4',4",4'''-tetra(2,4-diamino-1,3,5
      triazin-6-yl)tetraphenylethene. Activated HOF-5a exhibits a stepwise N2
      adsorption isotherm at 77 K, suggesting framework flexibility. The structure of
      activated HOF-5a has been established by powder X-ray diffraction studies,
      indicating a significant framework contraction from as-synthesized HOF-5 to
      activated HOF-5a of ~21% by volume. HOF-5a shows moderately high porosity with a
      Brunauer-Emmett-Teller (BET) surface area of 1101 m(2)/g, and takes up a large
      amount of acetylene and carbon dioxide under ambient conditions. Powder neutron
      diffraction studies and theoretical calculations reveal that suitable pore sizes,
      curvatures, and functional sites collectively enable HOF-5a to encapsulate a high
      density of carbon dioxide molecules packed in a pseudo-one-dimensional array
      along the pore channel. 

PMID- 26214342
TI  - Total Synthesis of (-)-N-Methylwelwitindolinone C Isothiocyanate Based on a Pd
      Catalyzed Tandem Enolate Coupling Strategy.
AB  - The highly stereocontrolled total synthesis of (-)-N-methylwelwitindolinone C
      isothiocyanate is described, which features the expeditious construction of a
      bicyclo[4.3.1]decane ring system by a palladium-catalyzed tandem enolate
      allylation/arylation reaction. 

PMID- 26214341
TI  - Pioglitazone for Hepatic Steatosis in HIV/Hepatitis C Virus Coinfection.
AB  - Chronic hepatitis C infection frequently coexists with human immunodeficiency
      virus (HIV) and together are associated with increased hepatic steatosis.
      Steatosis is a risk factor for progression of liver disease and may persist
      despite a sustained virologic response to hepatitis C treatment. Therefore,
      therapies to target hepatic steatosis are important for individuals with HIV and
      hepatitis C virus (HCV) coinfection. We completed a 48-week, randomized, double
      blind, placebo-controlled trial of pioglitazone (45 mg/day) in 13 subjects with
      HIV/HCV coinfection. The primary outcome variable was hepatic fat content,
      measured by magnetic resonance spectroscopy (MRS) imaging. Individuals randomized
      to pioglitazone had a significant decrease in hepatic fat content measured by MRS
      from baseline (15.1 +/- 7.0%) to week 48 (7.6 +/- 3.9%), with a mean difference
      of -7.4% (p = 0.02, n = 5). There was no significant change in hepatic fat
      content with placebo. Glycemic control as measured by oral glucose challenge
      improved significantly with pioglitazone (p = 0.047). Though not statistically
      significant, there were trends toward improved alanine aminotransferase (ALT) and
      histopathologic grade of steatosis in subjects who received pioglitazone.
      Pioglitazone was well tolerated and no one discontinued due to side effects. This
      study demonstrates that 48 weeks of pioglitazone therapy, and not placebo,
      results in significant reductions in hepatic fat content as measured by MRS in
      subjects with HIV and HCV coinfection and hepatic steatosis. This small study
      shows that pioglitazone helps ameliorate steatosis in the context of HIV/HCV
      coinfection. 

PMID- 26214343
TI  - Supramolecular Assembly of Artificial Metalloenzymes Based on the Dimeric Protein
      LmrR as Promiscuous Scaffold.
AB  - Supramolecular anchoring of transition metal complexes to a protein scaffold is
      an attractive approach to the construction of artificial metalloenzymes since
      this is conveniently achieved by self-assembly. Here, we report a novel design
      for supramolecular artificial metalloenzymes that exploits the promiscuity of the
      central hydrophobic cavity of the transcription factor Lactococcal multidrug
      resistance Regulator (LmrR) as a generic binding site for planar coordination
      complexes that do not provide specific protein binding interactions. The success
      of this approach is manifested in the excellent enantioselectivities that are
      achieved in the Cu(II) catalyzed enantioselective Friedel-Crafts alkylation of
      indoles. 

PMID- 26214344
TI  - Consideration of Future Consequences and HPV Vaccine Uptake Among Young Adults.
AB  - The authors investigated the effect of individual difference in consideration of
      future consequences (CFC) on the uptake of the HPV vaccine among a group of young
      adults. A cross-sectional survey of 676 college students was conducted. Findings
      indicated that CFC had no direct effect on HPV vaccine uptake. However, CFC had
      significant effects on a number of HPV-related health beliefs in that greater CFC
      was associated with less perceived susceptibility to HPV, greater perceived
      severity of HPV, less perceived logistic/financial barriers, and higher perceived
      vaccine efficacy. CFC exerted a significant indirect effect on vaccine uptake
      through perceived vaccine efficacy. Implications of the findings for health
      communication are discussed. 

PMID- 26214345
TI  - Hellmann-Feynman forces within the DFT + U in Wannier functions basis.
AB  - The most general way to describe localized atomic-like electronic states in
      strongly correlated compounds is to use Wannier functions. In the present paper
      we continue development of widely-used DFT + U method with the Wannier function
      basis set and propose a technique to calculate Hubbard contribution to atomic
      forces. The technique was implemented as a part of plane-waves pseudopotential
      code Quantum-ESPRESSO and tested on two compounds: charge transfer insulator NiO
      with cubic crystal structure and correlated metal SrVO3 with perovskite
      structure. 

PMID- 26214346
TI  - Regulatory and scientific issues in studies to evaluate sexual dysfunction in
      antidepressant drug trials.
AB  - OBJECTIVE: Sexual dysfunction is an important side effect of serotonergic
      antidepressants, as it often leads to treatment nonadherence. However, sexual
      dysfunction is often underestimated in clinical trials submitted in support of
      drug approval. This is because such assessments are based mainly on unsolicited
      reporting. As a result, the characterization of sexual adverse events has become
      an important component of many of the development programs for new
      antidepressants. The purpose of this article is to discuss US Food and Drug
      Administration's (FDA's) current thinking on possible approaches to
      characterizing the effects of drugs on sexual function in depression drug trials.
      PARTICIPANTS: FDA's Division of Psychiatry Products, together with the Division
      of Biometrics I, in particular the authors of this article. EVIDENCE: The above
      referenced FDA divisions conducted a regulatory science forum on measuring sexual
      dysfunction in depression trials. CONSENSUS PROCESS: Considering the evidence
      presented and discussed at the forum, we developed our preliminary regulatory
      views on the scientific issues with regard to study design, study population, use
      of available scales, testing strategy, and statistical analysis plans.
      CONCLUSIONS: Sexual dysfunction associated with antidepressants is an important
      entity that should be adequately assessed during clinical trials with the use of
      available instruments and described in product labels. It is important to
      appreciate the need for a positive control to establish assay sensitivity for any
      trial evaluating the impact of antidepressant medications on sexual function.
      Methodological improvement and additional data as well as experience with these
      approaches will be needed prior to further consideration of a formal regulatory
      guidance document by the FDA.

PMID- 26214348
TI  - Physiologically Based Pharmacokinetic Model for Inorganic and Methylmercury in a
      Marine Fish.
AB  - A physiologically based pharmacokinetic (PBPK) model was developed to simulate
      the uptake, distribution, and elimination of inorganic mercury [Hg(II)] and
      methylmercury (MeHg) in a marine fish, Terapon jarbua. In this model, fish were
      schematized as a six-compartment model by assuming that blood was the medium
      linking the exchange between the different compartments. The transfer rates
      between blood and other compartments were determined during a period of 10-day
      dietary Hg(II) or MeHg exposure, followed by a 30-day depuration. For both Hg
      species, the exchange rates between liver and blood were high, indicating that
      liver served as a "transferring station" in the distribution. Their accumulation
      in the kidney was relatively constant and low. The carcass (mainly muscle)
      represented a large sink for both Hg(II) and MeHg with the highest input rate
      constants and relatively lower output rate constants. Significant differences
      were observed in the rate constants between the two Hg species, suggesting great
      variations in their exchange and transportation routes. Modeling simulation for
      the first time demonstrated that the gill was the most important route in Hg(II)
      elimination in marine fish, with a rate constant of 0.90 d(-1). A long time frame
      is needed to study the exact rate of MeHg elimination in marine fish. This study
      showed that the PBPK modeling provided critical information for the uptake,
      distribution and elimination of Hg(II) and MeHg in the fish body, especially in
      elucidating the role of each compartment.

PMID- 26214347
TI  - Comparative Study of Different Methods for the Prediction of Drug-Polymer
      Solubility.
AB  - In this study, a comparison of different methods to predict drug-polymer
      solubility was carried out on binary systems consisting of five model drugs
      (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and
      polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer
      weight ratios. The drug-polymer solubility at 25  degrees C was predicted using
      the Flory-Huggins model, from data obtained at elevated temperature using thermal
      analysis methods based on the recrystallization of a supersaturated amorphous
      solid dispersion and two variations of the melting point depression method. These
      predictions were compared with the solubility in the low molecular weight liquid
      analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The
      predicted solubilities at 25  degrees C varied considerably depending on the
      method used. However, the three thermal analysis methods ranked the predicted
      solubilities in the same order, except for the felodipine-PVP system.
      Furthermore, the magnitude of the predicted solubilities from the
      recrystallization method and melting point depression method correlated well with
      the estimates based on the solubility in the liquid analogues, which suggests
      that this method can be used as an initial screening tool if a liquid analogue is
      available. The learnings of this important comparative study provided general
      guidance for the selection of the most suitable method(s) for the screening of
      drug-polymer solubility. 

PMID- 26214349
TI  - Steroid cell tumour, not otherwise specified: Rare case with primary amenorrhoea
      in a 16-year-old.

PMID- 26214350
TI  - The Burden of Pulmonary Nontuberculous Mycobacterial Disease in the United
      States.
AB  - RATIONALE: State-specific case numbers and costs are critical for quantifying the
      burden of pulmonary nontuberculous mycobacterial disease in the United States.
      OBJECTIVES: To estimate and project national and state annual cases of
      nontuberculous mycobacterial disease and associated direct medical costs.
      METHODS: Available direct cost estimates of nontuberculous mycobacterial disease
      medical encounters were applied to nontuberculous mycobacterial disease
      prevalence estimates derived from Medicare beneficiary data (2003-2007).
      Prevalence was adjusted for International Classification of Diseases, 9th
      Revision, undercoding and the inclusion of persons younger than 65 years of age.
      U.S. Census Bureau data identified 2010 and 2014 population counts and 2012
      primary insurance-type distribution. Medical costs were reported in constant 2014
      dollars. Projected 2014 estimates were adjusted for population growth and assumed
      a previously published 8% annual growth rate of nontuberculous mycobacterial
      disease prevalence. MEASUREMENTS AND MAIN RESULTS: In 2010, we estimated 86,244
      national cases, totaling to $815 million, of which 87% were inpatient related
      ($709 million) and 13% were outpatient related ($106 million). Annual state
      estimates varied from 48 to 12,544 cases ($503,000-$111 million), with a median
      of 1,208 cases ($11.5 million). Oceanic coastline states and Gulf States
      comprised 70% of nontuberculous mycobacterial disease cases but 60% of the U.S.
      population. Medical encounters among individuals aged 65 years and older ($562
      million) were twofold higher than those younger than 65 years of age ($253
      million). Of all costs incurred, medications comprised 76% of nontuberculous
      mycobacterial disease expenditures. Projected 2014 estimates resulted in 181,037
      national annual cases ($1.7 billion). CONCLUSIONS: For a relatively rare disease,
      the financial cost of nontuberculous mycobacterial disease is substantial,
      particularly among older adults. Better data on disease dynamics and more recent
      prevalence estimates will generate more robust estimates.

PMID- 26214351
TI  - Advancing the Assessment of Personality Pathology With the Cognitive-Affective
      Processing System.
AB  - The Cognitive-Affective Processing System (CAPS) is a dynamic and expansive model
      of personality proposed by Mischel and Shoda (1995) that incorporates
      dispositional and processing frameworks by considering the interaction of the
      individual and the situation, and the patterns of variation that result. These
      patterns of cognition, affect, and behavior are generally defined through the use
      of if ... then statements, and provide a rich understanding of the individual
      across varying levels of assessment. In this article, we describe the CAPS model
      and articulate ways in which it can be applied to conceptualizing and assessing
      personality pathology. We suggest that the CAPS model is an ideal framework that
      integrates a number of current theories of personality pathology, and
      simultaneously overcomes a number of limits that have been empirically identified
      in the past. 

PMID- 26214352
TI  - Toward nonsystemic delivery of therapeutics across the blood-brain barrier.

PMID- 26214353
TI  - Recent nanomedicine articles of outstanding interest: nanoparticle
      functionalization for disease diagnostics and therapy.

PMID- 26214354
TI  - Accumulation of amino-polyvinyl alcohol-coated superparamagnetic iron oxide
      nanoparticles in bone marrow: implications for local stromal cells.
AB  - AIMS: First, it will be investigated if amino-polyvinyl alcohol-coated
      superparamagnetic iron oxide nanoparticles (A-PVA-SPIONs) are suitable for MRI
      contrast enhancement in bone marrow. Second, the impact of A-PVA-SPION exposure
      in vivo on the viability and key functions of local bone marrow stromal cells
      (BMSCs) will be investigated. MATERIAL & METHODS: Animals were systemically
      injected with A-PVA-SPIONs, followed by a 7-day survival time. Accumulation of A
      PVA-SPIONs was confirmed by MRI, histology and inductively coupled plasma optical
      emission spectrometry. BMSCs were isolated from bone marrow for in vitro
      assessment of their viability and regenerative key functions. RESULTS: In this
      study, A-PVA-SPIONs were found to accumulate in bone marrow and increase the
      BMSCs' metabolic activity and migration rate. CONCLUSION: A-PVA-SPIONs appear
      suitable for contrast enhancement in bone marrow while our data suggest an
      influence on the BMSCs biology that necessitates future research.

PMID- 26214355
TI  - An efficient injectable formulation with block copolymer micelles for hydrophobic
      antitumor candidate-pyridazinone derivatives.
AB  - AIM: To make delivery improvements via delivery systems for 6-(4-morpholino-3
      (trifluoromethyl)phenyl)pyridazin-3(2H)-one (DZO) - a model compound of
      hydrophobic antitumor candidate pyridazinone derivatives. MATERIALS & METHODS:
      Methoxy poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PDLLA) micelle was employed
      as a vector, and DZO was encapsulated in. The DZO-loaded micelles were
      characterized in detail and its cytotoxicity, maximum tolerated dose (MTD) and
      pharmacokinetic experiments were done. In vivo anticancer activity was studied
      through a subcutaneous 4T1 tumor model. RESULTS: Compared with free DZO, the DZO
      loaded micelles possessed a sustained release property, an improved MTD, better
      pharmacokinetic parameters and an enhanced antitumor activity for subcutaneous
      4T1 model in vivo. CONCLUSION: An effective injectable delivery system for DZO
      was developed successfully.

PMID- 26214357
TI  - Nanocarriers for delivery of siRNA and co-delivery of siRNA and other therapeutic
      agents.
AB  - A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors
      have great advantages to solve the problem, if the bottleneck of their delivery
      could be well addressed by the various nanocarriers. Moreover, co-delivery of
      siRNA together with the various anticancer agents in one nanocarrier may maximize
      their additive or synergistic effect. This review provides a comprehensive
      summary on the state-of-the-art of the nanocarriers, which may include prodrugs,
      micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles,
      nanoparticles of biodegradable polymers and nucleic acid nanocarriers for
      delivery of siRNA and co-delivery of siRNA together with anticancer agents with
      focus on synthesis of the nanocarrier materials, design and characterization, in
      vitro and in vivo evaluation, and prospect and challenges of nanocarriers. 

PMID- 26214356
TI  - Arg-Gly-Asp-D-Phe-Lys peptide-modified PEGylated dendrimer-entrapped gold
      nanoparticles for targeted computed tomography imaging of breast carcinoma.
AB  - AIM: To investigate cyclo (Arg-Gly-Asp-D-Phe-Lys) peptide (RGD)-modified
      PEGylated dendrimer-entrapped gold nanoparticles (PEGylated Au DENPs-RGD) for
      targeted computed tomography (CT) imaging of breast carcinomas. MATERIALS &
      METHODS: PEGylated Au DENPs-RGD were synthesized and characterized. Then, the
      PEGylated Au DENPs-RGD for targeted CT imaging were investigated using the MDA-MB
      435 cell line, an integrin-rich breast carcinoma cells, and mice with MDA-MB-435
      xenograft tumors. Finally, silver enhancement staining and integrin alphavbeta3
      immunohistochemistry of the tumors were performed. RESULTS: The synthesized
      PEGylated Au DENPs-RGD were spherical, water dispersible and biocompatible
      nanoprobes with a gold nanoparticle core size of 2.8 nm. Due to the presence of
      the Au nanoparticles, the PEGylated Au DENPs-RGD displayed a higher x-ray
      attenuation intensity than Omnipaque at the same Au or I concentrations. The
      conjugated RGD ligand can specifically identify and target overexpressed integrin
      receptors on MDA-MB-435 cells. After intravenous injection, these nanoprobes
      accumulated in the targeted area of mice with MDA-MB-435 xenograft tumors, which
      enabled the tumor to be detected by CT imaging. The histological results
      confirmed the imaging results. CONCLUSION: The PEGylated Au DENPs-RGD can be used
      as targeted nanoprobes with good biocompatibility for targeted CT imaging and
      diagnosis of integrin-positive tumors.

PMID- 26214358
TI  - Therapeutic and safety considerations of nanoparticle-mediated drug delivery in
      pregnancy.
AB  - Advances in nanotechnology have resulted in the design of effective, safe and
      tissue-selective nanocarriers for delivering therapeutics to treat malignancies,
      infections and other diseases. In pregnancy, nanoparticle-based drug formulations
      could have the potential to selectively target either the placenta and/or fetus,
      enabling 'fetal-friendly' drugs to be administered in pregnancy with minimal risk
      of off-target effects. A considerable amount of research has been carried out on
      maternal-placental-fetal nanoparticle uptake, transfer and toxicity using rodent
      and ex vivo models. However, the development of placental targeting strategies
      and the therapeutic evaluation of nanoformulations in pregnancy remains in its
      infancy. While some promising avenues are currently under investigation, much
      work is needed to bring the advantages of nanoparticle-based drug therapy in
      pregnancy to clinical reality. 

PMID- 26214359
TI  - Carbohydrate-based materials for targeted delivery of drugs and genes to the
      liver.
AB  - The insult to liver by toxic materials leads to cirrhosis, hepatitis and cancer.
      Upon administration, drugs accumulate in liver, which is systemically cleared by
      reticuloendothelial system. However, specific targeting of drugs to liver is a
      serious challenge. Specific delivery of molecules to hepatocytes is accomplished
      by targeting cell surface lectins, asialoglycoprotein receptors. Asialofetuin, N
      acetyl glucosamine and galactose are high-affinity ligands of asialoglycoprotein
      receptors. The bioconjugation of drugs, fluorescent molecules and gene delivery
      vectors with lectin-targeting agents, and their delivery in liver hepatocytes, is
      discussed. Mannose and N-acetyl glucosamine conjugates are evaluated for their
      delivery to hepatic stellate and kupffer cells. The glycosylated gene and drug
      delivery vectors in clinical trials are outlined. 

PMID- 26214360
TI  - Co-Occurring Non-Suicidal Self-Injury and Firesetting Among At-Risk Adolescents:
      Experiences of Negative Life Events, Mental Health Problems, Substance Use, and
      Suicidality.
AB  - Co-occurring internalizing and externalizing problem behaviors in adolescence
      typically marks more severe psychopathology and poorer psychosocial functioning
      than engagement in a single problem behavior. We examined the negative life
      events, emotional and behavioral problems, substance use, and suicidality of
      school-based adolescents reporting both non-suicidal self-injury (NSSI) and
      repetitive firesetting, compared to those engaging in either behavior alone.
      Differences in NSSI characteristics among self-injurers who set fires, compared
      to those who did not, were also assessed. A total of 384 at-risk adolescents aged
      12-18 years (58.8% female) completed self-report questionnaires measuring NSSI,
      firesetting, and key variables of interest. Results suggest that adolescents who
      both self-injure and deliberately set fires represent a low-prevalence but
      distinct high-risk subgroup, characterized by increased rates of interpersonal
      difficulties, mental health problems and substance use, more severe self-injury,
      and suicidal behavior. Implications for prevention and early intervention
      initiatives are discussed. 

PMID- 26214361
TI  - Structural integrity of the limbic-prefrontal connection: Neuropathological
      correlates of anxiety in Williams syndrome.
AB  - Williams syndrome (WS) is a genetic condition characterized by a hypersocial
      personality and desire to form close relationships, juxtaposed with significant
      anxieties of nonsocial events. The neural underpinnings of anxiety in individuals
      with WS are currently unknown. Aberrations in the anatomical and microstructural
      integrity of the uncinate fasciculus (UF) have been recently implicated in social
      and generalized anxiety disorders. Based on these findings, we tested the
      hypothesis that the reported anxieties in individuals with WS share similar
      neuropathological correlates. Toward this end, diffusion tensor imaging (DTI)
      methods were employed to examine the microstructural integrity (fractional
      anisotropy, mean diffusivity, longitudinal diffusivity) of the UF in 18 WS and 15
      typically developing adults (TD). Anxiety and sociability questionnaires were
      administered to determine associations with DTI indices of UF across groups.
      Results revealed comparable white matter integrity of the UF across groups, yet
      elevated subjective experience of anxiety in those with WS. Additionally,
      sociability and UF microstructural properties were dissociated across both
      groups. Whereas no relationships were found between DTI indices and anxiety in TD
      participants, strong negative associations were observed between these constructs
      in individuals with WS. Findings indicated that increased anxiety manifested by
      individuals with WS was associated with DTI measures of the UF and may signal
      structural or possibly physiological aberration involving this tract within the
      prefrontal-temporal network. 

PMID- 26214363
TI  - Optically Pumped Two-Dimensional MoS2 Lasers Operating at Room-Temperature.
AB  - The discovery of direct bandgap semiconducting two-dimensional (2D) transition
      metal dichalcogenides (TMDCs) has opened a new era in flexible optoelectronic
      devices. Critical to this development is the realization of a semiconductor laser
      using the emerging 2D TMDCs. Here, by embedding 2D MoS2 at the interface between
      a free-standing microdisk and microsphere, we have demonstrated, for the first
      time, room-temperature lasing from 2D TMDCs. The devices exhibit multiple lasing
      peaks in the wavelength range of ~600 to 800 nm. The threshold is measured to be
      ~5 MUW under continuous wave operation at room temperature. No saturation in the
      output power is measured for pump powers more than 2 orders of magnitude larger
      than the threshold. The superior performance is attributed to the large gain of
      2D TMDCs and the strong coupling between the 2D MoS2 gain medium and optical
      modes in the unique optical cavity. 

PMID- 26214362
TI  - Subtle Chemical Shifts Explain the NMR Fingerprints of Oligomeric
      Proanthocyanidins with High Dentin Biomodification Potency.
AB  - The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the
      biomechanical properties of dentin involves collagen cross-linking of the 1.3-4.5
      nm wide space via protein-polyphenol interactions. A systematic interdisciplinary
      search for the bioactive principles of pine bark has yielded the trimeric PAC,
      ent-epicatechin-(4beta->8)-epicatechin-(2beta->O->7,4beta->8)-catechin (3),
      representing the hitherto most potent single chemical entity capable of enhancing
      dentin stiffness. Building the case from two congeneric PAC dimers, a detailed
      structural analysis decoded the stereochemistry, spatial arrangement, and
      chemical properties of three dentin biomodifiers. Quantum-mechanics-driven (1)H
      iterative full spin analysis (QM-HiFSA) of NMR spectra distinguished previously
      unrecognized details such as higher order J coupling and provided valuable
      information about 3D structure. Detection and quantification of H/D-exchange
      effects by QM-HiFSA identified C-8 and C-6 as (re)active sites, explain
      preferences in biosynthetic linkage, and suggest their involvement in dentin
      cross-linking activity. Mapping of these molecular properties underscored the
      significance of high delta precision in both (1)H and (13)C NMR spectroscopy.
      Occurring at low- to subppb levels, these newly characterized chemical shift
      differences in ppb are small but diagnostic measures of dynamic processes
      inherent to the OPAC pharmacophores and can help augment our understanding of
      nanometer-scale intermolecular interactions in biomodified dentin macromolecules.

PMID- 26214364
TI  - Chemical composition, cytotoxicity, antimicrobial and antifungal activity of
      several essential oils.
AB  - Essential oils (EOs) are known and used for their biological, antibacterial,
      antifungal and antioxidant properties. Numerous studies have shown that EOs
      exhibit a large spectrum of biological activities in vitro. The incidence of drug
      resistant pathogens and the toxicity of antibiotics have drawn attention to the
      antimicrobial activity of natural products, encouraging the development of
      alternative treatments. The aim of this study was to analyse the phytochemical
      and the cytotoxic characteristic of 36 EOs; we then evaluated the antimicrobial
      activity of the less-toxic EOs on Gram-positive, Gram-negative and fungi strains.
      The results showed low cytotoxicity in seven EOs and good activity against Gram
      negative and Candida spp. strains. Based on our results, EOs could be proposed as
      a novel group of therapeutic agents. Further experiments are necessary to confirm
      their pharmacological effectiveness, and to determine potential toxic effects and
      the mechanism of their activity in in vivo models. 

PMID- 26214366
TI  - Enthalpic Forces Correlate with the Selectivity of Transthyretin-Stabilizing
      Ligands in Human Plasma.
AB  - The plasma protein transthyretin (TTR) is linked to human amyloidosis.
      Dissociation of its native tetrameric assembly is a rate-limiting step in the
      conversion from a native structure into a pathological amyloidogenic fold.
      Binding of small molecule ligands within the thyroxine binding site of TTR can
      stabilize the tetrameric integrity and is a potential therapeutic approach.
      However, through the characterization of nine different tetramer-stabilizing
      ligands we found that unspecific binding to plasma components might significantly
      compromise ligand efficacy. Surprisingly the binding strength between a
      particular ligand and TTR does not correlate well with its selectivity in plasma.
      However, through analysis of the thermodynamic signature using isothermal
      titration calorimetry we discovered a better correlation between selectivity and
      the enthalpic component of the interaction. This is of specific interest in the
      quest for more efficient TTR stabilizers, but a high selectivity is an almost
      universally desired feature within drug design and the finding might have wide
      ranging implications for drug design. 

PMID- 26214365
TI  - Dynamics and Membrane Interactions of Protein Kinase C.
AB  - Protein kinase C (PKC) is a family of Ser/Thr kinases that regulate a multitude
      of cellular processes through participation in the phosphoinositide signaling
      pathway. Significant research efforts have been directed at understanding the
      structure, function, and regulatory modes of the enzyme since its discovery and
      identification as the first receptor for tumor-promoting phorbol esters. The
      activation of PKC involves a transition from the cytosolic autoinhibited latent
      form to the membrane-associated active form. The membrane recruitment step is
      accompanied by the conformational rearrangement of the enzyme, which relieves
      autoinhibitory interactions and thereby allows PKC to phosphorylate its targets.
      The multidomain structure and intrinsic flexibility of PKC present remarkable
      challenges and opportunities for the biophysical and structural biology studies
      of this class of enzymes and their interactions with membranes, the major focus
      of this Current Topic. I will highlight the recent advances in the field, outline
      the current challenges, and identify areas where biophysics and structural
      biology approaches can provide insight into the isoenzyme-specific regulation of
      PKC activity. 

PMID- 26214368
TI  - Critical Anomalies of Two SN1 Hydrolysis Reactions in Critical Binary Solutions.
AB  - Rates of SN1 hydrolysis reactions for 2-chloro-2-methylbutane in the critical
      solution of isobutyric acid + water and for 2-bromo-2-methylpropane in the
      critical solution of triethylamine + water in the one-phase region and at various
      temperatures have been determined respectively by conductance measurements. It
      was found that the reaction rates at different temperatures for those two SN1
      reactions were well described by the Arrhenius equation in the noncritical
      region, whereas near the critical points the critical slowing down was clearly
      detected. These results are inconsistent with a previous report in the literature
      (J. Phys. Chem. A 2003, 107, 8435 - 8443). Reanalyzing the literature data, we
      found that if an Arrhenius equation appropriate to either the one-phase region or
      the two-phase region being examined was used as the background, a critical
      slowing down rather than a speeding up was detected for the reaction in both the
      one-phase region and the two-phase region. The experimental data from different
      sources were fitted with a simplified crossover formalism characterizing the
      critical effect on the reactions to determine the critical slowing down
      exponents, which were found to be about 0.04, showing that only a dynamic
      critical slowing down could be detected for these reaction systems. This
      phenomenon was attributed to the fact that the SN1 hydrolysis reaction is neither
      a first-order nor a pseudo-first-order reaction in the reverse direction and the
      kinetic measurements were carried out in a region quite far from the equilibrium
      of the reactions.

PMID- 26214367
TI  - Structural basis for plasmepsin V inhibition that blocks export of malaria
      proteins to human erythrocytes.
AB  - Plasmepsin V, an essential aspartyl protease of malaria parasites, has a key role
      in the export of effector proteins to parasite-infected erythrocytes.
      Consequently, it is an important drug target for the two most virulent malaria
      parasites of humans, Plasmodium falciparum and Plasmodium vivax. We developed a
      potent inhibitor of plasmepsin V, called WEHI-842, which directly mimics the
      Plasmodium export element (PEXEL). WEHI-842 inhibits recombinant plasmepsin V
      with a half-maximal inhibitory concentration of 0.2 nM, efficiently blocks
      protein export and inhibits parasite growth. We obtained the structure of P.
      vivax plasmepsin V in complex with WEHI-842 to 2.4-A resolution, which provides
      an explanation for the strict requirements for substrate and inhibitor binding.
      The structure characterizes both a plant-like fold and a malaria-specific helix
      turn-helix motif that are likely to be important in cleavage of effector
      substrates for export. 

PMID- 26214370
TI  - Coding the direct/indirect pathways by D1 and D2 receptors is not valid for
      accumbens projections.
AB  - It is widely accepted that D1 dopamine receptor-expressing striatal neurons
      convey their information directly to the output nuclei of the basal ganglia,
      whereas D2-expressing neurons do so indirectly via pallidal neurons. Combining
      optogenetics and electrophysiology, we found that this architecture does not
      apply to mouse nucleus accumbens projections to the ventral pallidum. Thus,
      current thinking attributing D1 and D2 selectivity to accumbens projections akin
      to dorsal striatal pathways needs to be reconsidered. 

PMID- 26214369
TI  - LSD1n is an H4K20 demethylase regulating memory formation via transcriptional
      elongation control.
AB  - We found that a neuron-specific isoform of LSD1, LSD1n, which results from an
      alternative splicing event, acquires a new substrate specificity, targeting
      histone H4 Lys20 methylation, both in vitro and in vivo. Selective genetic
      ablation of LSD1n led to deficits in spatial learning and memory, revealing the
      functional importance of LSD1n in neuronal activity-regulated transcription that
      is necessary for long-term memory formation. LSD1n occupied neuronal gene
      enhancers, promoters and transcribed coding regions, and was required for
      transcription initiation and elongation steps in response to neuronal activity,
      indicating the crucial role of H4K20 methylation in coordinating gene
      transcription with neuronal function. Our results indicate that this alternative
      splicing of LSD1 in neurons, which was associated with altered substrate
      specificity, serves as a mechanism acquired by neurons to achieve more precise
      control of gene expression in the complex processes underlying learning and
      memory. 

PMID- 26214371
TI  - Oscillatory dynamics coordinating human frontal networks in support of goal
      maintenance.
AB  - Humans have a capacity for hierarchical cognitive control-the ability to
      simultaneously control immediate actions while holding more abstract goals in
      mind. Neuropsychological and neuroimaging evidence suggests that hierarchical
      cognitive control emerges from a frontal architecture whereby prefrontal cortex
      coordinates neural activity in the motor cortices when abstract rules are needed
      to govern motor outcomes. We utilized the improved temporal resolution of human
      intracranial electrocorticography to investigate the mechanisms by which frontal
      cortical oscillatory networks communicate in support of hierarchical cognitive
      control. Responding according to progressively more abstract rules resulted in
      greater frontal network theta phase encoding (4-8 Hz) and increased prefrontal
      local neuronal population activity (high gamma amplitude, 80-150 Hz), which
      predicts trial-by-trial response times. Theta phase encoding coupled with high
      gamma amplitude during inter-regional information encoding, suggesting that inter
      regional phase encoding is a mechanism for the dynamic instantiation of complex
      cognitive functions by frontal cortical subnetworks. 

PMID- 26214374
TI  - Human upper-limb force capacities evaluation with robotic models for ergonomic
      applications: effect of elbow flexion.
AB  - The aim of this study was to apply models derived from the robotics field to
      evaluate the human upper-limb force generation capacity. Four models were
      compared: the force ellipsoid (FE) and force polytope (FP) based on unit joint
      torques and the scaled FE (SFE) and scaled FP (SFP) based on maximum isometric
      joint torques. The four models were assessed from four upper-limb postures with
      varying elbow flexion (40 degrees , 60 degrees , 80 degrees  and 100 degrees )
      measured by an optoelectronic system and their corresponding isometric joint
      torques. Ten subjects were recruited. Three specific ellipsoids and polytopes
      parameters were compared: isotropy, principal force orientation and volume.
      Isotropy showed that the ellipsoids and polytopes were elongated. The angle
      between the two ellipsoids main axis and the two polytopes remained low but
      increased with the elbow flexion. The FE and FP volumes increased and those of
      SFE and SFP decreased with the elbow flexion. The interest and limits of such
      models are discussed in the framework of ergonomics and rehabilitation. 

PMID- 26214372
TI  - Determinants of different deep and superficial CA1 pyramidal cell dynamics during
      sharp-wave ripples.
AB  - Sharp-wave ripples represent a prominent synchronous activity pattern in the
      mammalian hippocampus during sleep and immobility. GABAergic interneuronal types
      are silenced or fire during these events, but the mechanism of pyramidal cell
      (PC) participation remains elusive. We found opposite membrane polarization of
      deep (closer to stratum oriens) and superficial (closer to stratum radiatum) rat
      CA1 PCs during sharp-wave ripples. Using sharp and multi-site recordings in
      combination with neurochemical profiling, we observed a predominant inhibitory
      drive of deep calbindin (CB)-immunonegative PCs that contrasts with a prominent
      depolarization of superficial CB-immunopositive PCs. Biased contribution of
      perisomatic GABAergic inputs, together with suppression of CA2 PCs, may explain
      the selection of CA1 PCs during sharp-wave ripples. A deep-superficial gradient
      interacted with behavioral and spatial effects to determine cell participation
      during sleep and awake sharp-wave ripples in freely moving rats. Thus, the firing
      dynamics of hippocampal PCs are exquisitely controlled at subcellular and
      microcircuit levels in a cell type-selective manner. 

PMID- 26214373
TI  - Identification of neurodegenerative factors using translatome-regulatory network
      analysis.
AB  - For degenerative disorders of the CNS, the main obstacle to therapeutic
      advancement has been the challenge of identifying the key molecular mechanisms
      underlying neuronal loss. We developed a combinatorial approach including
      translational profiling and brain regulatory network analysis to search for key
      determinants of neuronal survival or death. Following the generation of
      transgenic mice for cell type-specific profiling of midbrain dopaminergic
      neurons, we established and compared translatome libraries reflecting the
      molecular signature of these cells at baseline or under degenerative stress.
      Analysis of these libraries by interrogating a context-specific brain regulatory
      network led to the identification of a repertoire of intrinsic upstream
      regulators that drive the dopaminergic stress response. The altered activity of
      these regulators was not associated with changes in their expression levels. This
      strategy can be generalized for the identification of molecular determinants
      involved in the degeneration of other classes of neurons. 

PMID- 26214375
TI  - The impact of structural modification of 1,2,4-thiadiazole derivatives on
      thermodynamics of solubility and hydration processes.
AB  - The influence of a structural modification on thermodynamic aspects of solubility
      and hydration processes of 1,2,4-thiadiazole drug-like compounds was
      investigated. A substitution in the phenyl ring of the 1,2,4-thiadiazole molecule
      leads to a significant decrease of the solubility of these compounds. In order to
      rationalize the relationship between the structures of 1,2,4-thiadiazoles and
      their solubility, the latter was considered in terms of two fundamental
      processes: sublimation and hydration. It was found that for most of the compounds
      solubility decline is a result of a differently directed action of the
      sublimation and hydration contributions, i.e., the introduction of substituents
      leads to the simultaneous growth of the sublimation Gibbs energy and decrease in
      the hydration Gibbs energy. 

PMID- 26214376
TI  - Solvation Dynamics of Trimethylamine N-Oxide in Aqueous Solution Probed by
      Terahertz Spectroscopy.
AB  - We have studied the hydration dynamics of trimethylamine N-oxide (TMAO) in
      aqueous solution using a combination of concentration-dependent terahertz/far
      infrared (THz/FIR) and Raman spectroscopic techniques. Terahertz/FIR absorption
      was measured using narrowband (76-93 cm(-1)) p-Ge laser and broad band (30-400
      cm(-1)) Fourier transform spectroscopy. We used principal component analysis in
      combination with a semi-ideal chemical equilibrium model to dissect the spectra
      into linear and nonlinear contributions of the solvated solute extinction. We
      attribute the linear part to the average extinction and Raman scattering of TMAO
      water aggregates with approximately 3-4 water strongly hydrogen bonded to TMAO.
      An additional nonlinear concentration dependence indicates a decrease of the
      number of attached water molecules with increasing TMAO concentrations due to a
      shift in association equilibria. The Raman spectra reveal a frequency shift of
      the (narrowband) intramolecular vibrations with decreasing dilution. Based on the
      results of a detailed analysis and isotopic substitution, the experimentally
      observed absorption bands at 0, 176, and 388 cm(-1) could be assigned to water
      relaxation modes, an intermolecular TMAO-H2O stretch, and the C-N-C bending mode,
      respectively. Our results provide evidence for a local modification of the water
      structure. 

PMID- 26214377
TI  - Limiting early mortality: Do's and don'ts in the management of patients with
      newly diagnosed multiple myeloma.
AB  - In the era of novel biological agents, multiple myeloma (MM) is often approached
      as a chronic condition. While survival continues to improve, population-level
      data indicate that early mortality remains a substantial barrier to advances in
      MM outcomes. Here we provide "do's and don'ts" management recommendations that
      may minimize the risk of early mortality and ensure that patients have the
      opportunity to benefit from the long term impact of new effective MM agents. Such
      recommendations encompass the early introduction of novel agents even in the
      presence of comorbidities and advanced age and aggressive management of MM
      related complications.

PMID- 26214378
TI  - Solution-processed assembly of ultrathin transparent conductive cellulose
      nanopaper embedding AgNWs.
AB  - Natural biomass based cellulose nanopaper is becoming a promising transparent
      substrate to supersede traditional petroleum based polymer films in realizing
      future flexible paper-electronics. Here, ultrathin, highly transparent,
      outstanding conductive hybrid nanopaper with excellent mechanical flexibility was
      synthesized by the assembly of nanofibrillated cellulose (NFC) and silver
      nanowires (AgNWs) using a pressured extrusion paper-making technique. The hybrid
      nanopaper with a thickness of 4.5 MUm has a good combination of transparent
      conductive performance and mechanical stability using bamboo/hemp NFC and AgNWs
      cross-linked by hydroxypropylmethyl cellulose (HPMC). The heterogeneous fibrous
      structure of BNFC/HNFC/AgNWs endows a uniform distribution and an enhanced
      forward light scattering, resulting in high electrical conductivity and optical
      transmittance. The hybrid nanopaper with an optimal weight ratio of BNFC/HNFC to
      AgNWs shows outstanding synergistic properties with a transmittance of 86.41% at
      550 nm and a sheet resistance of 1.90 ohm sq(-1), equal to the electronic
      conductivity, which is about 500 S cm(-1). The BNFC/HNFC/AgNW hybrid nanopaper
      maintains a stable electrical conductivity after the peeling test and bending at
      135 degrees  for 1000 cycles, indicating remarkably strong adhesion and
      mechanical flexibility. Of importance here is that the high-performance and low
      cost hybrid nanopaper shows promising potential for electronics application in
      solar cells, flexible displays and other high-technology products. 

PMID- 26214379
TI  - Skin sites to predict deep-body temperature while wearing firefighters' personal
      protective equipment during periodical changes in air temperature.
AB  - The aim of this study was to investigate stable and valid measurement sites of
      skin temperatures as a non-invasive variable to predict deep-body temperature
      while wearing firefighters' personal protective equipment (PPE) during air
      temperature changes. Eight male firefighters participated in an experiment which
      consisted of 60-min exercise and 10-min recovery while wearing PPE without self
      contained breathing apparatus (7.75 kg in total PPE mass). Air temperature was
      periodically fluctuated from 29.5 to 35.5  degrees C with an amplitude of 6 
      degrees C. Rectal temperature was chosen as a deep-body temperature, and 12 skin
      temperatures were recorded. The results showed that the forehead and chest were
      identified as the most valid sites to predict rectal temperature (R(2) = 0.826
      and 0.824, respectively) in an environment with periodically fluctuated air
      temperatures. This study suggests that particular skin temperatures are valid as
      a non-invasive variable when predicting rectal temperature of an individual
      wearing PPE in changing ambient temperatures. Practitioner Summary: This study
      should offer assistance for developing a more reliable indirect indicating system
      of individual heat strain for firefighters in real time, which can be used
      practically as a precaution of firefighters' heat-related illness and utilised
      along with physiological monitoring. 

PMID- 26214380
TI  - Psoriasis in the US Medicare Population: Prevalence, Treatment, and Factors
      Associated with Biologic Use.
AB  - Psoriasis is a common chronic inflammatory disorder, primarily of the skin.
      Despite an aging population, knowledge of the epidemiology of psoriasis and its
      treatments among the elderly is limited. We examined the prevalence of psoriasis
      and its treatments, with a focus on biologics and identification of factors
      associated with biologic use, using a nationally representative sample of
      Medicare beneficiaries in 2011. On the basis of several psoriasis identification
      algorithms, the claims-based prevalence for psoriasis in the United States ranged
      from 0.51 to 1.23%. Treatments used for moderate-to-severe psoriasis
      (phototherapy, oral systemic, or biologic therapies) were received by 27.3% of
      the total psoriasis sample, of whom 37.2% used biologics. Patients without a
      Medicare Part D low-income subsidy (LIS) had 70% lower odds of having received
      biologics than those with LIS (odds ratio 0.30; 95% confidence interval, 0.19
      0.46). Similarly, the odds of having received biologics were 69% lower among
      black patients compared with white patients (0.31; 0.16-0.60). This analysis
      identified potential financial and racial barriers to receipt of biologic
      therapies and underscores the need for additional studies to further define the
      epidemiology and treatment of psoriasis among the elderly. 

PMID- 26214381
TI  - Hyaluronidase-1 Is Mainly Functional in the Upper Granular Layer, Close to the
      Epidermal Barrier.

PMID- 26214382
TI  - Androgens Attenuate Vitamin D Production Induced by UVB Irradiation of the Skin
      of Male Mice by an Enzymatic Mechanism.
AB  - Cutaneous exposure to UVB irradiation is an important source of vitamin D. Here,
      we examined sex-specific differences in cutaneous vitamin D production in mice.
      Both male and female mice on a vitamin D-deficient diet manifested vitamin D
      deficiency, with mineral abnormalities, secondary hyperparathyroidism, and
      osteomalacia. UVB irradiation significantly increased vitamin D levels in the
      skin of female mice and normalized serum 25-hydroxyvitamin D3 and 1,25
      dihydroxyvitamin D3 levels, as well as mineral and skeletal abnormalities.
      However, in male mice, the vitamin D response to UVB was attenuated and mineral
      and skeletal abnormalities were not normalized. The vitamin D precursor, 7
      dehydrocholesterol (7DHC), was significantly lower in the skin of male than
      female mice. This reduction was due to local androgen action in the skin as
      demonstrated by castration studies and skin-specific androgen receptor deletion
      in male mice, both of which reversed the male phenotype. Local androgen
      regulation in the skin of the CYP11A1 gene, which encodes a crucial enzyme that
      metabolizes cholesterol, 7DHC, and vitamin D, appeared to contribute to the
      gender differences in UVB-induced vitamin D production and to its reversal of
      vitamin D deficiency. Sex-specific, enzymatically regulated differences in
      cutaneous production of vitamin D may therefore be of importance to ensure
      vitamin D sufficiency. 

PMID- 26214383
TI  - FRET sensor-based quantification of intracellular trehalose in mammalian cells.
AB  - Trehalose acts as a stress protectant and an autophagy inducer in mammalian
      cells. The molecular mechanisms of action remain obscure because intracellular
      trehalose at micromolar level is difficult to quantitate. Here, we show a novel
      trehalose monitoring technology based on FRET. FLIP-suc90MU?1Venus sensor
      expressed in mammalian cells enables to quickly and non-destructively detect an
      infinitesimal amount of intracellular trehalose.

PMID- 26214385
TI  - Redox-dependent self-sorting toggles a rotary nanoswitch.
AB  - The pyridine-pyrimidine (py-pym) arm as the moving part of the two-state
      nanomechanical rotary switch [Cu(1)](+) is toggled reversibly between two
      stations using one-electron oxidation/reduction. In state I, the arm is attached
      via Cu(+) complexation to a sterically encumbered phenanthroline and in state II
      to a zinc porphyrin station. Toggling is realised by charging and discharging an
      external input signal, the ferrocene-appended diimine ligand 2. Addition of 2
      leads to formation of the intermolecular complex [Cu(1)(2)](+) paralleled by a
      move of the py-pym arm to the zinc porphyrin station. Upon oxidation at the
      ferrocenyl unit, 2(+) detaches from [Cu(1)(2)](2+) so that [Cu(1)](+) is formed
      in state I. Switching was ascertained by NMR, UV-Vis spectroscopy and cyclic
      voltammetry. 

PMID- 26214384
TI  - Efficient heterocyclisation by (di)terpene synthases.
AB  - While cyclic ether forming terpene synthases are known, the basis for such
      heterocyclisation is unclear. Here it is reported that numerous (di)terpene
      synthases, particularly including the ancestral ent-kaurene synthase, efficiently
      produce isomers of manoyl oxide from the stereochemically appropriate substrate.
      Accordingly, such heterocyclisation is easily accomplished by terpene synthases.
      Indeed, the use of single residue changes to induce production of the appropriate
      substrate in the upstream active site leads to efficient bifunctional enzymes
      producing isomers of manoyl oxide, representing novel enzymatic activity. 

PMID- 26214386
TI  - A Chronic, Nonhealing Wound of the Finger Caused by Polypropylene Suture
      Material.
AB  - Chronic wounds usually result from poor peripheral circulation, neuropathy,
      pressure, radiation, or infection. Such common types of chronic wounds are easily
      diagnosed and managed with traditional wound care techniques. In contrast,
      chronic nonhealing wounds caused by cancerous skin lesions, mycobacterial
      infections, and foreign-body reactions that are refractory to traditional wound
      therapy present a particular diagnostic challenge, resulting in erroneous or
      delayed diagnosis. Therefore, an unusual presentation of a chronic wound should
      be taken into account when establishing differential diagnosis. In an effort to
      enhance recognition of chronic wounds caused by foreign-body reactions and
      facilitate their proper management, the authors report a case of a chronic
      nonhealing wound on the dorsum of a finger that was associated with the use of
      polypropylene suture and lasted for 3 years. 

PMID- 26214387
TI  - Epidemiologic Trends in Neonatal Intensive Care, 2007-2012.
AB  - IMPORTANCE: Neonatal intensive care has been highly effective at improving
      newborn outcomes but is expensive and carries inherent risks. Existing studies of
      neonatal intensive care have focused on specific subsets of newborns and lack a
      population-based perspective. OBJECTIVES: To describe admission rates to neonatal
      intensive care units (NICUs) for US newborns across the entire continuum of birth
      weight and how these rates have changed across time, as well as describe the
      characteristics of infants admitted to NICUs. DESIGN, SETTING, AND PARTICIPANTS:
      An epidemiologic time-trend analysis was conducted on April 1, 2015, of live
      births (>=500 g) from January 1, 2007, to December 31, 2012, to residents of 38
      US states and the District of Columbia, recorded using the 2003 revision of the
      US Standard Certificate of Live Birth (N = 17,896,048). EXPOSURE: Birth year.
      MAIN OUTCOMES AND MEASURES: Crude, stratified (by birth weight), and adjusted
      admission rates. Trends in birth weight, gestational age, weight for gestational
      age, and use of assisted ventilation are presented to describe the cohort of
      admitted newborns. RESULTS: In 2012, there were 43.0 NICU admissions per 1000
      normal-birth-weight infants (2500-3999 g), while the admission rate for very low
      birth-weight infants (<1500 g) was 844.1 per 1000 live births. Overall, admission
      rates during the 6-year study period increased from 64.0 to 77.9 per 1000 live
      births (relative rate, 1.22; 95% CI, 1.21-1.22 [P < .001]). Admission rates
      increased for all birth weight categories. Trends in relative rates adjusted for
      maternal and newborn characteristics showed a similar 23% increase (95% CI, 1.22
      1.23 [P < .001]). During the study period, newborns admitted to a NICU were
      larger and less premature, although no consistent trend was seen in weight for
      gestational age or the use of assisted ventilation. CONCLUSIONS AND RELEVANCE:
      After adjustment for infant and maternal risk factors, US newborns at all birth
      weights are increasingly likely to be admitted to a NICU, which raises the
      possibility of overuse of neonatal intensive care in some newborns. Further study
      is needed into the causes of the increased use observed in our study as well as
      its implications for payers, policymakers, families, and newborns.

PMID- 26214388
TI  - A non-regular layer arrangement of a pillared-layer coordination polymer:
      avoiding interpenetration via symmetry breaking at nodes.
AB  - A coordination terpolymerization strategy is introduced to alter the connectivity
      within layers of a pillared-layer coordination polymer. Assembling two different
      dicarboxylate linkers around a metal cluster in the layer suppresses
      interpenetration while enabling formation of a rectangular 2D grid structure. 

PMID- 26214389
TI  - Selective refinement and selection of near-native models in protein structure
      prediction.
AB  - In recent years in silico protein structure prediction reached a level where
      fully automated servers can generate large pools of near-native structures.
      However, the identification and further refinement of the best structures from
      the pool of models remain problematic. To address these issues, we have developed
      (i) a target-specific selective refinement (SR) protocol; and (ii) molecular
      dynamics (MD) simulation based ranking (SMDR) method. In SR the all-atom
      refinement of structures is accomplished via the Rosetta Relax protocol, subject
      to specific constraints determined by the size and complexity of the target. The
      best-refined models are selected with SMDR by testing their relative stability
      against gradual heating through all-atom MD simulations. Through extensive
      testing we have found that Mufold-MD, our fully automated protein structure
      prediction server updated with the SR and SMDR modules consistently outperformed
      its previous versions.

PMID- 26214391
TI  - A systematic review of the effectiveness of whole-of-community interventions by
      socioeconomic position.
AB  - Whole-of-community (WOC) interventions have led to modest reductions in
      population weight gain. Whether they exhibit differential effectiveness by
      socioeconomic position (SEP) remains unknown. We aimed to summarize evidence of
      differential effectiveness of WOC interventions by SEP. Electronic databases and
      grey literature were searched to identify studies that evaluated the
      effectiveness of a WOC intervention on behavioural change measures, energy
      balance behaviours and/or anthropometric outcomes according to any measure of
      SEP. Interventions were assessed for the following characteristics: structural
      changes to the environment, number of settings the intervention acted in,
      presence of community engagement and whether equity was considered in its design.
      Ten studies were included. Nine reported a greater or equal effect among low SEP
      groups compared with high SEP groups. These studies commonly featured
      interventions that incorporated structural changes to the environment, acted
      across more than three settings and/or employed community engagement. Conclusions
      did not change when excluding low-quality studies (n = 4). WOC interventions
      represent an effective and equitable approach for the reduction of population
      weight. Structural components, a larger number of settings and community
      engagement were common in equitable WOC interventions and should be considered in
      the design of future WOC interventions.

PMID- 26214394
TI  - Big Bad Bill is sweet William now.

PMID- 26214395
TI  - Drug Manufacturers' Delayed Disclosure of Serious and Unexpected Adverse Events
      to the US Food and Drug Administration.

PMID- 26214396
TI  - T cells are the critical source of IL-4/IL-13 in a mouse model of allergic
      asthma.
AB  - BACKGROUND: IL-4 and IL-13 play a crucial role during allergic asthma. Both
      cytokines can be produced by T cells and a variety of cell types of the innate
      immune system. The relative contribution of T-cell-derived vs innate IL-4/IL-13
      for allergic inflammation and airway hyperreactivity remains unclear. METHODS: We
      compared the severity of OVA/alum-induced allergic lung inflammation in WT BALB/c
      mice to mice that lack expression of IL-4/IL-13 only in T cells (4-13Tko) or in
      all cell types (4-13ko). RESULTS: T-cell-derived IL-4/IL-13 was required for IgG1
      and IgE production, recruitment of eosinophils and basophils to the lung, goblet
      cell hyperplasia, expression of Muc5ac, Clca3, and RELMbeta, differentiation of
      alternatively activated macrophages, and airway hyperreactivity. Interestingly,
      ILC2 recruitment to the lung occurred independently of T-cell-derived IL-4/IL-13
      but was diminished in the absence of IL-4/IL-13 from all cell types. Thus, the
      number of IL-4/IL-13-competent ILC2s did not correlate with the severity of lung
      pathology. CONCLUSIONS: Th2 cells appear to be the critical IL-4/IL-13-expressing
      cell type for the induction of allergic airway inflammation and airway
      hyperreactivity. The translational perspective of our results indicates that
      inhibition or reprogramming of Th2 cells may be very effective for the treatment
      of allergic asthma.

PMID- 26214397
TI  - Measles Outbreak as a Catalyst for Stricter Vaccine Exemption Legislation.

PMID- 26214398
TI  - Sialoblastoma. diagnosis by FNAC: A case report.
AB  - Tumors of salivary gland are very uncommon in children and comprise of <5% of all
      salivary gland tumors. Most of these neoplasms originate in the parotid gland
      with 10-15% arising from the submandibular, sublingual, and minor salivary
      glands. We report a case of sialoblastoma in an 8-year-old male child who
      presented with a history of slowly progressive swelling of the parotid gland
      since birth, which was soft to firm in consistency and mobile in all directions.
      Magnetic resonance imaging showed a well encapsulated tumor located in the
      superficial lobe of the left parotid gland. Fine needle aspiration was performed,
      which revealed a parotid tumor with closest resemblance to sialoblastoma.
      Superficial parotidectomy was performed. The histopathology confirmed the
      diagnosis of sialoblastoma. Sialoblastoma should always be considered when the
      lesion is known or suspected to be congenital.

PMID- 26214399
TI  - Geminiviruses for biotechnology: the art of parasite taming.
AB  - Viruses are intracellular pathogens that have evolved efficient strategies for
      replication and expression of their proteins in the host cells. Geminiviruses -
      plant viruses with small circular single-stranded DNA genomes - effectively
      manipulate plant cell processes for viral functions, entailing great potential
      for biotechnological applications. This potentiality has been realized in the
      form of protein expression and gene-silencing vectors, and, more recently,
      vectors for genome editing - a technology that these viruses seem particularly
      well-suited to facilitate. This insight offers an overview of the biological
      properties of geminiviruses, with emphasis on those leveraging development of
      geminivirus-based replicons. It illustrates the basis for engineering geminivirus
      based replicons and their applications. Furthermore, it discusses the reported
      use and future perspectives of geminivirus-based replicons for genome editing.

PMID- 26214400
TI  - Molecular pillar supported graphene oxide framework: conformational heterogeneity
      and tunable d-spacing.
AB  - n-Alkylamines were grafted on the basal plane oxygen functionalities of graphene
      oxide (GO), yielding molecular pillar supported graphene oxide frameworks (GOFs)
      with tunable interlayer spacing. A major fraction of n-alkylamines was found to
      covalently interact with the basal plane epoxy groups via nucleophilic
      substitution reactions. The d-spacing in GOFs could be tailored between 10.5 and
      28.9 A by varying the chain length of the n-alkylamines. (13)C SSNMR explicitly
      showed the coexistence of both trans and gauche conformation modes. The relative
      populations of these modes control the conformational heterogeneity and
      orientation of n-alkylamines in the GOFs. A plausible bilayer structural model of
      the GOFs was demonstrated. The terminal methyl and methylene units of the n
      alkylamines grafted on the GO basal plane were interdigitated with the counter
      layer and afforded a double-layer structure of alkyl chain supported GOFs. 

PMID- 26214401
TI  - Formic acid oxidation on platinum: a simple mechanistic study.
AB  - The oxidation of small organic acids on noble metal surfaces under
      electrocatalytic conditions is important for the operation of fuel cells and is
      of scientific interest, but the basic reaction mechanisms continue to be a matter
      of debate. Formic acid oxidation on platinum is one of the simplest of these
      reactions, yet even this model system remains poorly understood. Historically,
      proposed mechanisms for the oxidation of formic acid involve the acid molecule as
      a reactant, but recent studies suggest that the formate anion is the reactant. Ab
      initio studies of this reaction do not address formate as a possible reactant,
      likely because of the difficulty of calculating a charged species near a charged
      solvated surface under potential control. Using the recently-developed joint
      density functional theory (JDFT) framework for electrochemistry, we perform ab
      initio calculations on a Pt(111) surface to explore this reaction and help
      resolve the debate. We find that when a formate anion approaches the platinum
      surface at typical operating voltages, with H pointing towards the surface, it
      reacts to form CO2 and adsorbed H with no barrier on a clean Pt surface. This
      mechanism leads to a reaction rate proportional to formate concentration and
      number of available platinum sites. Additionally, high coverages of adsorbates
      lead to large reaction barriers, and consequently, we expect the availability of
      metal sites to limit the experimentally observed reaction rate. 

PMID- 26214402
TI  - Toward Zero Micro/Macro-Scale Wear Using Periodic Nano-Layered Coatings.
AB  - Wear is an important phenomenon that affects the efficiency and life of all
      moving machines. In this regard, extensive efforts have been devoted to achieve
      the lowest possible wear in sliding systems. With the advent of novel materials
      in recent years, technology is moving toward realization of zero wear. Here, we
      report on the development of new functional coatings comprising periodically
      stacked nanolayers of amorphous carbon and cobalt that are extremely wear
      resistant at the micro and macro scale. Because of their unique structure, these
      coatings simultaneously provide high elasticity and ultrahigh shear strength. As
      a result, almost zero wear was observed even after one million sliding cycles
      without any lubrication. The wear rate was reduced by 8-10-fold compared with the
      best previously reported data on extremely low wear materials. 

PMID- 26214403
TI  - N'-Alkylaminosulfonyl Analogues of 6-Fluorobenzylideneindolinones with Desirable
      Physicochemical Profiles and Potent Growth Inhibitory Activities on
      Hepatocellular Carcinoma.
AB  - The benzylideneindolinone 6-chloro-3-(3'-trifluoromethylbenzylidene)-1,3
      dihydroindol-2-one (4) was reported to exhibit potent and selective growth
      inhibitory effects on hepatocellular carcinoma (HCC). Corroborative evidence
      supported multi-receptor tyrosine kinase (RTK) inhibition as a possible mode of
      action. However, the poor physicochemical properties of 4 limited its furtherance
      as a lead compound. In this study, the modification of 4 was investigated with
      the aim of improving its potency and physicochemical profile. The 6
      fluorobenzylideneindolinone 3-12 bearing a 3'-N-propylaminosulfonyl substituent
      was found to be a promising substitute. Compound 3-12 [6-fluoro-3-(3'-N
      propylaminosulfonylbenzylidene)-1,3-dihydroindol-2-one] was found to be tenfold
      more soluble than 4 and to have sub-micromolar growth inhibitory activities on
      HCC cells. It is apoptogenic and inhibits the phosphorylation of several RTKs in
      HuH7, of which the inhibition of FGFR4 and HER3 are prominent. Compound 3-12
      decreased the tumor load in a physiologically relevant orthotopic HCC xenograft
      murine model. Structure-activity relationships support pivotal roles for the
      fluoro and N'-propylaminosulfonyl moieties in enhancing cell-based activity and
      moderating the physicochemical profile (solubility, permeability) of 3-12. 

PMID- 26214404
TI  - Effects of isoflurane preconditioning in the delayed phase on myocardial tumor
      necrosis factor alpha levels and caspase-3 protein expression in a rabbit model
      of ischemia-reperfusion injury.
AB  - This study aimed to investigate the protective effects and the mechanisms
      underlying these effects of isoflurane preconditioning in the delayed phase of
      myocardial ischemia-reperfusion injury. We randomly divided 30 healthy male New
      Zealand white rabbits into three groups with 10 rabbits in each group as follows:
      sham operation group (C group), ischemia-reperfusion group (I/R group), and 2.0%
      isoflurane preconditioning group (S group). Rabbits in the C group received
      thoracotomy for 160 min. Rabbits in the I/R group underwent left coronary artery
      occlusion for 40 min and reperfusion for 120 min. Rabbits in the S group received
      inhalation of 2.0% isoflurane and 100% oxygen for 2 h; after 24 h, rabbits in
      this group received the same treatment as that administered to rabbits in the I/R
      group. We examined the tumor necrosis factor alpha (TNF-alpha) levels in each
      group 20 min before occlusion of the left coronary, 20 and 40 min after occlusion
      of the left coronary artery, and 1 and 2 h after myocardial reperfusion. After
      reperfusion, immunoblotting was used to measure the myocardial caspase-3
      expression levels, and the infarct size was measured using Evans blue and
      tetrazolium chloride staining. The levels of TNF-alpha and caspase-3 were lower
      in the S group than in the I/R group, and the myocardial infarct size decreased
      in the S group. Thus, isoflurane preconditioning in the delayed phase exerted
      protective effects by decreasing the myocardial caspase-3 expression and TNF
      alpha production in a rabbit model of ischemia-reperfusion injury. 

PMID- 26214405
TI  - Development of microsatellite markers for Hancornia speciosa Gomes (Apocynaceae).
AB  - Herein, we describe 34 microsatellite loci developed using an enrichment genomic
      library for the tree species Hancornia speciosa Gomes (Apocynaceae). Thirty-five
      individuals were genotyped using 34 primers to analyze the polymorphisms at each
      locus. The number of alleles per locus ranged from 4 to 20. The average number of
      alleles was 8.11, and the expected heterozygosity ranged from 0.62 to 0.94. These
      microsatellite primers will be useful in population genetics studies for this
      species. 

PMID- 26214406
TI  - MicroRNAs as novel biomarkers for the differentiation of malignant versus benign
      thyroid lesions: a meta-analysis.
AB  - The aim of this meta-analysis was to systematically evaluate the diagnostic
      accuracy of microRNAs (miRNAs) in distinguishing malignant thyroid lesions from
      benign ones and to determine the potential of miRNAs as diagnostic biomarkers for
      thyroid cancer. The random-effect model was used to summarize the pooled
      estimates of diagnostic accuracy, including sensitivity, specificity, positive
      likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds
      ratio (DOR). The summary receiver-operating characteristic curve (SROC) and area
      under the SROC curve (AUC) were used to further evaluate the overall diagnostic
      value. Overall, 20 studies from 7 articles, including 266 thyroid cancer patients
      and 277 controls with benign thyroid disease, were available for analysis. The
      pooled sensitivity, specificity, PLR, NLR, and DOR were: 0.78 (95%CI = 0.74
      0.81), 0.73 (95%CI = 0.69-0.77), 3.17 (95%CI = 2.28-4.40), 0.30 (95%CI = 0.23
      0.39), and 12.6 (95%CI = 8.26-19.4), respectively, and the AUC value was 0.85.
      The multiple miRNA assay yielded better diagnostic performance than the single
      miRNA assay, with sensitivity of 0.90 versus 0.75, specificity of 0.86 versus
      0.71, PLR of 6.14 versus 2.71, NLR of 0.13 versus 0.36, DOR of 44.5 versus 8.81,
      and AUC of 0.95 versus 0.82, suggesting that the multiple miRNA assay is a more
      credible method for thyroid cancer detection. In summary, miRNA assays,
      especially multiple miRNA assays, may play an important role as a second-line
      diagnostic tool to improve the diagnostic accuracy of fine needle aspiration
      biopsy in indeterminate lesions. However, further studies are warranted to
      confirm our findings.

PMID- 26214407
TI  - Correlation of CD4+ CD25+ Foxp3+ Treg with the recovery of joint function after
      total knee replacement in rats with osteoarthritis.
AB  - In this study, we observed changes in CD4(+) CD25(+) Foxp3(+) Treg expression in
      rats with osteoarthritis (OA) to explore the role that CD4(+) CD25(+) Foxp3(+)
      Treg plays in the decline in the condition of OA rats. Thirty rats were randomly
      divided into 2 groups equally and OA was induced in rats in the model group by
      injection of papain and l-cysteine into the right knee joint. Cartilage lesions
      were scored by the modified Mankin scale; pulmonary function was assessed by
      spirometry; interleukin (IL)-17 and IL-4 levels were evaluated by the enzyme
      linked immunosorbent assay; and the levels of CD4(+) CD25(+) Foxp3(+) Treg in
      peripheral blood were measured by flow cytometry. The left knee joints of the
      model rats appeared palpable swelling and osteophytes, while the body weight,
      heart and lung function of these rats decreased. The serum IL-4 level was lower,
      whereas the serum IL-17 level was higher in the model group (P < 0.05). The
      peripheral blood CD4(+) CD25(+) Foxp3(+) Treg of CD4(+)T cells was significantly
      lower. Correlation of the changes in the levels of IL-4, IL-17, and Treg suggests
      that the underlying mechanism may be a reduction of the regulatory effect of
      Treg. The specific mechanism still requires further study. 

PMID- 26214408
TI  - Biotechnological prospecting of foliar endophytic fungi of guaco (Mikania
      glomerata Spreng.) with antibacterial and antagonistic activity against
      phytopathogens.
AB  - Mikania glomerata (Spreng.), popularly known as "guaco", is a plant from the
      Asteraceae family that has many therapeutic properties. The use of medicinal
      plants has been examined in studies on endophytic diversity and bioprospecting;
      endophytes inhabit the interior of plants without harming them. Microorganism
      host complex interactions are related to the production of compounds that may
      confer resistance to pathogens or to production of bioactive compounds or growth
      regulators. In this study, we evaluated foliar endophytic fungi of M. glomerata
      to examine the control of plant pathogens, molecular identification, and
      production of compounds with antimicrobial activity. In the antagonism test, 6-mm
      diameter disks were placed equidistant from the endophyte and plant pathogen, and
      pathogen growth area was measured. The endophytic strains G-01, G-02, and G-03
      were effective against Fusarium solani and Didymella bryoniae. The endophyte rDNA
      regions corresponding to internal transcribed spacer 1-5.8S-internal transcribed
      spacer 2 were sequenced, and the results were compared with sequences deposited
      in the NCBI database. The G-01, G-02, and G-03 strains were identified as
      Diaporthe citri. This identification was confirmed by phylogenetic analysis. The
      crude extract of the secondary metabolites of the G-01 strain was tested against
      Escherichia coli and Staphylococcus aureus; the metabolites showed antimicrobial
      activity against S. aureus. The endophytes tested in this study have potential
      for use in biotechnological applications. 

PMID- 26214409
TI  - Allele frequencies of combined DNA index system (CODIS) and non-CODIS short
      tandem repeat loci in Goias, Central Brazil.
AB  - In studies of human identification, obtaining a high standard of outcomes and
      satisfactory conclusions are directly related to the use of highly polymorphic
      molecular markers. In addition to the combined DNA index system (CODIS) group, it
      is also important to implement non-CODIS markers into the analysis, as they
      increase the power of discrimination. During the identification process, it is
      essential to consider the genetic variation among distinct groups of populations,
      as the allele frequencies are directly associated with the power of
      discrimination. However, the population of Goias, a State located in Central
      Brazil, is characterized by a highly mixed population due to its diverse ethnic
      origins. In this study, a survey of the allelic frequencies in the Goias
      population was carried out using a molecular assembly composed of 21 autosomal
      loci both from and external to the CODIS group. The new data, for some of the
      markers used, were statistically similar to those from previous studies. This
      consistency means that the use of these markers might serve as a parameter for
      future population comparisons. The results from these analyses further our
      knowledge of the study of human identification. 

PMID- 26214410
TI  - Wnt1-induced MAFK expression promotes osteosarcoma cell proliferation.
AB  - Osteosarcoma is one of the most common primary bone tumors in children and young
      adults. In this study, we investigated the role of musculoaponeurotic
      fibrosarcoma oncogene homolog K (MAFK) in osteosarcoma cell proliferation in
      vitro and the possible pathways that contributed to MAFK-related osteosarcoma
      development. We first reported that MAFK was expressed at low levels in an
      osteosarcoma cell line. Furthermore, a significant correlation between MAFK and
      the Wnt signaling pathway was observed in osteosarcoma by using a gene microarray
      assay. We found that expression of MAFK could be induced by Wnt1 in a dose
      dependent manner. Furthermore, Wnt1-induced MAFK expression caused a significant
      increase of cell viability, whereas a Wnt pathway inhibitor, IWR-1-endo,
      abolished Wnt1-induced effects on MAFK. Finally, cell cycle analysis showed that
      enhanced cell proliferation might be attributed to re-distribution of the cell
      cycle. Together, our results suggested that Wnt1-induced MAFK expression promoted
      cell proliferation in MG63 cells, and that the role of MAFK in osteosarcoma might
      be closely linked to the Wnt signaling pathway. 

PMID- 26214412
TI  - Phenotypic correlations between ovum pick-up in vitro production traits and
      pregnancy rates in Zebu cows.
AB  - The growth of the Gyr breed in Brazil in terms of genetic gain for milk, along
      with conditions for market, has led to the use of ovum pick-up in vitro
      production (OPU-IVP) as a leader in biotechnology for the multiplication of
      genetic material. The aim of this study was to investigate phenotypic
      correlations between OPU-IVP-linked characteristics and pregnancy rates
      registered in an embryo transfer program using Gyr cows as oocyte donors. Data
      collected from 211 OPU sessions and 298 embryo transfers during the years 2012
      and 2013 were analyzed and statistical analysis was performed. Estimates of
      simple Pearson correlations were calculated for NVcoc and PVcoc (number and
      proportion of viable cumulus-oocyte complexes, respectively); NcleavD4 and
      PcleavD4 (number and proportion of cleaved embryos on day 4 of culture,
      respectively); NTembD7 and PTembD7 (number and proportion of transferable embryos
      on day 7 of culture, respectively); NPrD30 and PPrD30 (number and proportion of
      pregnancies 30 days after transfer, respectively); and NPrD60 and PPrD60 (number
      and proportion of pregnancies 60 days after transfer, respectively). Moderate to
      moderately high correlations were found for all numerical characteristics,
      suggesting these as the most suitable parameters for selection of oocyte donors
      in Gyr programs. NVcoc is proposed as a selection trait due to positive
      correlations with percentage traits and pregnancy rates 30 and 60 days after
      transfer. 

PMID- 26214411
TI  - Genetic polymorphism in sex hormone metabolism and prostate cancer risk.
AB  - We compared single-nucleotide polymorphisms for point mutations in cytochrome
      P450 genes, including cytochrome P450c17alpha (CYP17), cytochrome P450 aromatase
      (CYP19), steroid-5-a-reductase (SRD5A2), and prostate-specific antigen (PSA)
      involved in androgen and estrogen production. Between January 2008 and January
      2010, 90 patients were enrolled in the study. Of these patients, 28 were
      diagnosed with benign prostatic hyperplasia and 32 with prostate cancer, while 30
      subjects were included as a control group. CYP19 1531 C>T, SRD5A2 gene V89L,
      CYP17 gene -34 T/C, PSA-158 (G/A) regions were evaluated for the association
      between polymorphisms and benign prostatic hyperplasia and prostate cancer in
      study population. Age, body mass index, peak urinary flow rate (Q max), voided
      urine volume, post-void residual urine volume, total PSA, free PSA, free/total
      PSA ratio, prostate weights measured by transrectal ultrasonography, erectile
      dysfunction score, and international prostate symptom score were compared between
      groups. No statistically significant difference in CYP19 1531 C>T, SRD5A2 V89L,
      and CYP17 -34T/C was observed in both groups when compared to the control group.
      The homozygote variant of PSA- 158 (G/A) was significantly lower for prostate
      cancer. Age, total PSA, free PSA, free/total PSA ratio, prostate weight, and Q
      max were evaluated using multi-variant analysis. Only Q max was significant for
      the homozygote variant. The probability of being homozygous was 5.8- fold higher
      in subjects with Q max >14 mL/s. In the Turkish population, the homozygote
      variant of PSA-158 (G/A) was significantly lower for prostate cancer.

PMID- 26214413
TI  - Functional molecular markers (EST-SSR) in the full-sib reciprocal recurrent
      selection program of maize (Zea mays L.).
AB  - This study aimed to improve grain yield in the full-sib reciprocal recurrent
      selection program of maize from the North Fluminense State University. In the
      current phase of the program, the goal is to maintain, or even increase, the
      genetic variability within and among populations, in order to increase heterosis
      of the 13th cycle of reciprocal recurrent selection. Microsatellite expressed
      sequence tags (EST-SSRs) were used as a tool to assist the maximization step of
      genetic variability, targeting the functional genome. Eighty S1 progenies of the
      13th recur-rent selection cycle, 40 from each population (CIMMYT and Piranao),
      were analyzed using 20 EST-SSR loci. Genetic diversity, observed heterozygosity,
      information content of polymorphism, and inbreeding co-efficient were estimated.
      Subsequently, analysis of genetic dissimilarity, molecular variance, and a
      graphical dispersion of genotypes were conducted. The number of alleles in the
      CIMMYT population ranged from 1 to 6, while in the Piranao population the range
      was from 2 to 8, with a mean of 3.65 and 4.35, respectively. As evidenced by the
      number of alleles, the Shannon index showed greater diversity for the Piranao
      population (1.04) in relation to the CIMMYT population (0.89). The genic SSR
      markers were effective in clustering genotypes into their respective populations
      before selection and an increase in the variation between populations after
      selection was observed. The results indicate that the study populations have
      expressive genetic diversity, which cor-responds to the functional genome,
      indicating that this strategy may contribute to genetic gain, especially in
      association with the grain yield of future hybrids.

PMID- 26214414
TI  - Characterization and expression analysis of microRNAs in Qira black sheep and
      Hetian sheep ovaries using Solexa sequencing.
AB  - The role of microRNAs (miRNAs) in the regulation of mammalian reproduction has
      been demonstrated previously. However, only a few studies have assessed the role
      of miRNAs in the reproduction processes of sheep. The elucidation of miRNA
      expression profiles in the ovaries of different sheep breeds representing
      fecundity extremes will be useful in understanding the roles of miRNAs in sheep
      reproduction. In this study, two small RNA libraries were constructed from ovary
      tissue taken from Qira black sheep and Hetian sheep during the estrous period and
      then sequenced using the Solexa sequencing method. We obtained 9,565,212 and
      9,563,426 high-quality reads from Qira black sheep and Hetian sheep,
      respectively. In total, 531 miRNAs, including 98 putative miRNAs, were
      identified. Among the conserved miRNAs, 125 known miRNAs were significantly
      differentially expressed in the Qira black sheep and Hetian sheep libraries, with
      24 upregulated and 101 downregulated in the Hetian sheep compared to the Qira
      black sheep. Four differentially expressed miRNAs were analyzed using real-time
      quantitative PCR to validate the reliability of the Solexa sequencing results.
      These results provide a foundation for future research on the regulation of
      miRNAs in sheep fertility and enrich the sheep miRNA databases. 

PMID- 26214415
TI  - Codon usage bias analysis for the spermidine synthase gene from Camellia sinensis
      (L.) O. Kuntze.
AB  - The spermidine synthase (SPDS) gene exists widely in all types of plants. In this
      paper, the codon usage of the SPDS gene from Camellia sinensis (CsSPDS) was
      analyzed. The results showed that the codon usage of the CsSPDS gene is biased
      towards the T-ended or A-ended codons, which is similar to that observed in 73
      genes selected from the C. sinensis genome. An ENC-plot for 15 SPDS genes from
      various plant species suggested that mutational bias was the major factor in
      shaping codon usage in these genes. Codon usage frequency analysis indicated that
      there was little difference between the CsSPDS gene and dicot genomes, such as
      Arabidopsis thaliana and Nicotiana tabacum, but significant differences in codon
      usage were observed between the CsSPDS gene and monocot genomes, such as Triticum
      aestivum and Zea mays. Therefore, A. thaliana and N. tabacum expression systems
      may be more suitable for the expression of the CsSPDS gene.

PMID- 26214416
TI  - Correlation between the BRAF V600E mutation status and the clinicopathologic
      features of papillary thyroid carcinoma.
AB  - This study sought to investigate the correlations of V-raf murine sarcoma viral
      oncogene homolog B1 (BRAF) gene mutations with the clinicopathologic features of
      papillary thyroid carcinoma and central lymph node metastasis. We retrospectively
      analyzed the 2-year medical records of patients who underwent surgery for
      papillary thyroid carcinoma. After screening, the records of 126 patients who met
      the study requirements were used to assess the characteristics associated with
      the BRAF V600E gene mutation. The BRAF mutation incidence rate among patients
      with papillary thyroid carcinoma was 69.0% (87/126). Univariate analysis revealed
      that the BRAF mutation status was correlated significantly with both tumor size
      and lymph node metastasis (P < 0.05). Multivariate analysis revealed a
      significant correlation between lymph node metastasis and BRAF mutation status (P
      < 0.05). When the tumor diameter was <=10 mm, the BRAF mutation status had no
      effect on lymph node metastasis (P > 0.05). When the tumor diameter was >10 mm,
      the incidence of lymph node metastasis was significantly higher among BRAF
      mutation-positive patients than among BRAF mutation-negative patients (P < 0.05).
      BRAF gene mutations independently predicted central lymph node metastasis in
      patients with papillary thyroid carcinoma. For patients preoperatively diagnosed
      to be BRAF mutation-positive, the importance of central lymph node dissection
      should be emphasized because the tumor diameter increases; regional lymphatic and
      adipose tissue dissection should be routinely conducted. However, in mutation
      negative patients with tumor diameters of <=5 mm, the need for central lymph node
      dissection should be re-examined. 

PMID- 26214417
TI  - Temporal and tissue expression of genes involved in buds of earliness cotton
      cultivar.
AB  - Gene sequences previously identified in Arabidopsis buds were used as references
      in order to estimate temporal and tissue expression in buds, leaves, stem, and
      root tissues in cotton plants. Buds were evaluated during 3 phases: 2-8, 10-12,
      and 14-20 mm. Primers were designed for the ARF6, ATFY, and SEUSS genes for use
      in semi-quantitative reverse transcription-polymerase chain reaction and
      quantitative reverse transcription-polymerase chain reaction. Different levels of
      expression of the 3 genes were confirmed in cotton buds as well as in other
      tissues. The peak of gene expression was observed in buds sized 10-12 mm, after
      which expression decreased in larger buds. The gene GhFYPP3 was the most
      promising for further prospection of promoter regions, with regular expression
      patterns observed in bud sizes 10-12 and 14-20 mm. This trait was not observed in
      others genes. 

PMID- 26214418
TI  - rbcS SRS4 promoter from Glycine max and its expression activity in transgenic
      tobacco.
AB  - The regulatory region of the ribulose-1,5-bisphosphate carboxylase small subunit
      gene SRS4 from soybean (Glycine max) was cloned using TAIL-PCR and general PCR,
      and named the rbcS promoter. The promoter was fused with the GUS gene and
      introduced into Nicotiana tabacum via Agrobacterium-mediated leaf disk
      transformation. In 4-week-old transgenic tobacco plants, the highest GUS
      expression levels were observed in the leaves, GUS activity was 7.13- and 7.40
      fold higher in leaves than in stems and roots, respectively. Moreover, GUS
      activity was stimulated by light. In conclusion, spatial and light regulation of
      the soybean rbcS promoter was observed in N. tabacum, thus illustrating a leaf
      specific and light-induced promoter.

PMID- 26214419
TI  - Characterization and expression of the calpastatin gene in Cyprinus carpio.
AB  - Calpastatin, an important protein used to regulate meat quality traits in
      animals, is encoded by the CAST gene. The aim of the present study was to clone
      the cDNA sequence of the CAST gene and detect the expression of CAST in the
      tissues of Cyprinus carpio. The cDNA of the C. carpio CAST gene, amplified using
      rapid amplification of cDNA ends PCR, is 2834 bp in length (accession No.
      JX275386), contains a 2634-bp open reading frame, and encodes a protein with 877
      amino acid residues. The amino acid sequence of the C. carpio CAST gene was 88,
      80, and 59% identical to the sequences observed in grass carp, zebrafish, and
      other fish, respectively. The C. carpio CAST was observed to contain four
      conserved domains with 54 serine phosphorylation loci, 28 threonine
      phosphorylation loci, 1 tyrosine phosphorylation loci, and 6 specific protein
      kinase C phosphorylation loci. The CAST gene showed widespread expression in
      different tissues of C. carpio. Surprisingly, the relative expression of the CAST
      transcript in the muscle and heart tissues of C. carpio was significantly higher
      than in other tissues (P < 0.01). 

PMID- 26214420
TI  - Genetic diversity in intraspecific hybrid populations of Eucommia ulmoides Oliver
      evaluated from ISSR and SRAP molecular marker analysis.
AB  - Eucommia ulmoides Oliver, the only extant species of Eucommiaceae, is a second
      category state-protected endangered plant in China. Evaluation of genetic
      diversity among some intraspecific hybrid populations of E. ulmoides Oliver is
      vital for breeding programs and further conservation of this rare species. We
      studied the genetic diversity of 130 accessions from 13 E. ulmoides intraspecific
      hybrid populations using inter-simple sequence related (ISSR) and sequence
      related amplified polymorphism (SRAP) markers. Of the 100 ISSR primers and 100
      SRAP primer combinations screened, eight ISSRs and eight SRAPs were used to
      evaluate the level of polymorphism and discriminating capacity. A total number of
      65 bands were amplified using eight ISSR primers, in which 50 bands (76.9%) were
      polymorphic, with an average of 8.1 polymorphic fragments per primer.
      Alternatively, another 244 bands were observed using eight SRAP primer
      combinations, and 163 (66.8%) of them were polymorphic, with an average of 30.5
      polymorphic fragments per primer. The unweighted pair-group method (UPGMA)
      analysis showed that these 13 populations could be classified into three groups
      by the ISSR marker and two groups by the SRAP marker. Principal coordinate
      analysis using SRAP was completely identical to the UPGMA-based clustering,
      although this was partly confirmed by the results of UPGMA cluster analysis using
      the ISSR marker. This study provides insights into the genetic background of E.
      ulmoides intraspecific hybrids. The progenies of the variations "Huazhong-3",
      "big fruit", "Yanci", and "smooth bark" present high genetic diversity and offer
      great potential for E. ulmoides breeding and conservation. 

PMID- 26214421
TI  - Meta-analysis of the association between the HNF1B rs4430796 (A>G) polymorphism
      and risk of prostate cancer based on case-control studies.
AB  - Genome-wide studies have reported an association between the HNF1B rs4430796
      (A>G) polymorphism and prostate cancer risk, but results have been inconsistent
      and recent meta-analyses have been inadequate. This study aimed to integrate
      previous results and explore the validity of this association. Electronic
      searches for all relevant publications through May 18, 2014, were conducted
      across several databases. Additional studies were identified manually, and only
      the most recent or complete were used in this meta-analysis. Crude odds ratios
      (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the
      association. Seven eligible case-control studies were identified, incorporating a
      total of 14,049 patients and 12,674 controls. Overall, we found that the
      rs4430796 (A>G) polymorphism had a decreased risk of prostate cancer (GG vs AA:
      OR = 0.661, 95%CI = 0.615-0.710, P = 0.304; AG vs AA: OR = 0.782, 95%CI = 0.739
      0.828, P = 0.435; dominant model: OR = 0.743, 95%CI = 0.704-0.784, P = 0.912;
      recessive model: OR = 0.764, 95%CI = 0.718-0.813, P = 0.01). Furthermore, in the
      stratified analysis, there were significantly decreased risks among studies with
      population- and hospital-based controls. In the subgroup analysis by ethnicity,
      significantly decreased risks were also found among Caucasians, Americans, and
      Asians. Our results suggested that the HNF1B rs4430796 (A>G) polymorphism
      decreased the risk of prostate cancer. In the future, additional and larger
      studies on patients from across of the world might be required to validate our
      findings.

PMID- 26214422
TI  - Anastomosis groups and molecular variation in Pseudocercospora griseola.
AB  - The fungus Pseudocercospora griseola is the causal agent of angular leaf spot, a
      common bean (Phaseolus vulgaris L.) disease. The successful development of
      angular leaf spot-resistant cultivars depends on understanding the levels of
      variability in pathogen populations. P. griseola shows great pathogenic and
      genetic variation using inoculation on differential bean cultivars and molecular
      markers. Nevertheless, how this variability develops is not clearly understood.
      Parasexuality has been presented as a mechanism used by asexual fungi to increase
      variation. Hyphal fusion is the first step for the parasexual cycle, and it can
      be considered an additional trait for population studies. The aim of this study
      was to identify hyphal fusion (anastomosis) among P. grisola isolates and to
      evaluate the variability of isolates using analyses of anastomosis groups and
      RAPD markers. Hyphal anastomosis was observed in all isolates. Three isolates
      showed 85.0% compatibility and were compatible with 17 isolates. This is the
      first report of the occurrence of anastomosis between P. griseola isolates.
      Sixteen anastomosis groups were observed and only one group was formed by five
      isolates (Pg-01, Pg-02, Pg-07, Pg-08, and Pg-12). There was a large number of
      anastomosis groups and absence of clustering among isolates for hyphal fusion,
      demonstrating the existence of genetic variability for loci involved in the
      control of this trait. High genotypic variability by RAPD markers was detected,
      but there was no relationship between genotype and anastomosis group. More
      studies are necessary to elucidate further the process of asexual recombination
      in this phytopathogen. 

PMID- 26214424
TI  - Meiotic behavior and chromosome number of Urochloa adspersa (Trin.) R. D. Webster
      from the Brazilian Chaco.
AB  - This is the first report of meiotic division in Uro-chloa adspersa (Trin.)
      collected from the Brazilian Chaco. Meiotic analyses were performed on three
      specimens of U. adspersa named G10, G15, and G16. Inflorescences were collected
      and fixed in a mixture of ethanol and acetic acid (3:1, v/v) for 24 h and then
      stored in 70% alcohol. Diakinesis revealed different chromosome numbers and
      ploidy levels. All three plants were polyploids: G10 and G15 exhibited 2n = 6x =
      54 chromosomes (arranged in 27 bivalents), while G16 exhibited 2n = 4x = 36
      chromosomes (18 bivalents). Meiotic behavior was mainly normal in the hexaploid
      G15 and the tetraploid G16 (5.3 and 6.2% of the cells were abnormal, respective
      ly), revealing only a few meiotic abnormalities that are common to polyploids,
      i.e., those related to irregular chromosome segregation. G10 exhibited other
      meiotic abnormalities during meiosis II, such as chromosome stickiness, irregular
      spindle orientation, and irregular cytokinesis, which led to the formation of a
      few triads, resulting in 16.9% of the cells being abnormal. The origin of these
      abnormalities is discussed, and we suggest that the genes that control meiotic
      steps may be present in the Urochloa gene pool. 

PMID- 26214423
TI  - Forkhead box protein O1 mediates apoptosis in a cancer cervical cell line treated
      with the antitumor agent tumor necrosis factor-alpha.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important pro-apoptotic cytokine,
      which performs a broad range of immune and inflammatory functions in several
      vital processes. TNF-alpha-induced apoptosis has been confirmed, however,
      relatively little is known regarding the role of forkhead box class-O 1 (FOXO1)
      in mediating TNF-alpha-induced apoptosis in cervical cancer. In our study, we
      used the well-characterized cervical cancer cell line C-33A to investigate the
      role of FOXO1. The results showed that the antitumor agent TNF-alpha increased
      the expression level of FOXO1 (P < 0.05) and enhanced its transcriptional
      activity (P < 0.05). Furthermore, knockdown of FOXO1 repressed TNF-alpha-induced
      apoptosis and caspase-3, 8, and 9 expressions (P < 0.05). Collectively, these
      findings suggest that TNF-alpha upregulated the transcriptional factor FOXO1,
      leading to an increased expression of apoptotic gene, which leads to an increase
      in apoptosis. 

PMID- 26214425
TI  - Boswellic acid attenuates asthma phenotype by downregulation of GATA3 via
      nhibition of PSTAT6.
AB  - To study the role of boswellic acid in reducing asthma phenotype severity and the
      relationship between the expression of pSTAT6 and GATA3, thirty-six mice were
      randomly divided into normal control group, asthma group, and boswellic acid
      group (treatment group). The asthma model was established through an
      intraperitoneal injection of sensitization liquid (0.15 mL aluminum hydroxide gel
      at 88.67 mg/mL and 0.05 mg ovalbumin). pSTAT6 and GATA3 expression levels in
      peripheral blood were detected by reverse transcription-polymerase chain reaction
      and Western blot analysis. pSTAT6 and GATA3 gene expressions in the asthmatic
      group were significantly higher than in the normal control group; they were
      markedly lower in the treatment group than the asthma group, and there was no
      significant difference when compared with the normal control group. The pSTAT6
      expressions in the asthma, control and treatment groups were 2.256 +/- 0.125,
      0.524 +/- 0.210, and 0.897 +/- 0.134 at gray level, respectively. The GATA3
      expressions in the asthma, control, and treatment groups were 3.521 +/- 0.631,
      0.435 +/- 0.136, and 0.743 +/- 0.149 at gray level, respectively. pSTAT6 and
      GATA3 expression levels were similar in the treatment and control groups. GATA3
      expression had a positive correlation with pSTAT6 expression. Boswellic acid may
      improve asthma symptoms by inhibiting pSTAT6 expression, which consequently
      reduces GATA3 expression. 

PMID- 26214426
TI  - Transcriptomic identification of chemoreceptor genes in the red palm weevil
      Rhynchophorus ferrugineus.
AB  - Olfaction is crucial for insects' survival because it enables them to recognize
      various environmental information. It is primarily mediated by a large family of
      chemoreceptors, including olfactory receptors (ORs), gustatory receptors (GRs),
      and ionotropic receptors (IRs). Here, we assembled the transcriptome of the
      economically important pest of palms, Rhynchophorus ferrugineus, to reveal its
      chemoreceptor gene repertoire. About 8.08 Gbp data were generated using a HiSeq
      platform and their assembly led to a total of 24,439 unigenes. Among the
      transcripts, 12,523 (51.24%) showed significant similarity (E-value <10(-5)) to
      known proteins in the National Center for Biotechnology Information Nr database.
      From these sequences, 18 candidate genes of ORs were identified. Nine putative
      transcripts were homologous to GR genes, while 9 were similar to IR genes. The
      expression profiles of all identified chemoreceptor genes were determined by
      quantitative real-time PCR in antenna, head, thorax, abdomen, and legs of both
      sexes. Most chemoreceptor genes were antenna-enriched. This study demonstrated a
      successful application of a transcriptome for discovering a large number of
      divergent chemoreceptor genes of a non-model organism. The findings provide a
      valuable sequence resource and gene tissue distribution information for
      systematic functional analysis of molecular mechanisms underlying chemoreception
      in this pest.

PMID- 26214427
TI  - Effect of melatonin on oncosis of myocardial cells in the myocardial
      ischemia/reperfusion injury rat and the role of the mitochondrial permeability
      transition pore.
AB  - We aimed to evaluate the effect of melatonin on myo-cardial cell oncosis in the
      myocardial ischemia/reperfusion injury rat, and the role of the mitochondrial
      permeability transition pore (MPTP) therein. Sprague Dawley rats (N = 60) were
      randomly divided into five groups of 12 rats each: control, ischemia/reperfusion
      (I/R), melatonin treatment (MT), melatonin treatment + atractyloside (MT+ATR),
      and atractyloside (ATR). We prepared the myocardial ischemia/reperfusion model by
      reperfusion after the left anterior descending coronary artery was ligated for 30
      min. The MT rats were given a 10 mg/kg MT intra-venous injection immediately
      thereafter; the MT+ATR rats were also given a 5 mg/kg ATR intravenous injection
      15 min before the ischemia; the ATR rats were given the ATR injection only. After
      2-h re-perfusion, myocardial tissue was extracted, the infarction size was
      determined, and myocardial ultrastructures were observed using electron
      microscopy. The expression level of the preoncosis receptor (porimin), which can
      induce membrane injury, was determined by western blot; the nicotinamide adenine
      dinucleotide (NAD(+)) content was determined spectrophotometrically. The four
      treatment groups showed upregulat-ed expression of myocardial porimin, increased
      myocardial infarction size, and reduced NAD(+) content (P < 0.05). Compared with
      the I/R and MT+ATR groups, MT rats showed downregulated expression of myo-cardial
      porimin, reduced myocardial infarct size, and increased myo-cardial cell NAD(+)
      content (P < 0.05). The above indices between the ATR and MT+ATR groups were not
      significantly different (P > 0.05). Thus, MT might protect myocardial
      ischemia/reperfusion rats by inhibiting MPTP opening and reducing myocardial cell
      oncosis.

PMID- 26214428
TI  - Proton pump inhibitor use and risk of spontaneous bacterial peritonitis in
      cirrhotic patients: a systematic review and meta-analysis.
AB  - We used a meta-analysis approach to investigate the association between proton
      pump inhibitor (PPI) use and risk of spontaneous bacterial peritonitis (SBP) in
      cirrhotic patients. We searched Ovid Medline, Embase, and the Cochrane Library to
      identify eligible studies. We included studies that compared cirrhotic patients
      who did or did not use PPIs. The primary outcome was SBP, and the secondary
      outcome was overall bacterial infection. Results were pooled using random-effect
      models. This process led to identification of 12 journal articles and 5
      conference abstracts. The pooled data showed that PPI use in patients with
      cirrhosis and ascites was significantly associated with an increased risk of SBP
      [odds ratio (OR) = 2.17; 95% confidence interval (CI) = 1.46-3.23; P < 0.05; I2 =
      85.6%] and overall risk of bacterial infection (OR = 1.98; 95%CI = 1.36-2.87; P <
      0.05; I2 = 0). Subgroup analysis revealed that journal articles and studies
      reporting adjusted effect estimates demonstrated that PPI users had a
      significantly increased risk of SBP (OR = 2.13; 95%CI = 1.61-2.82; P < 0.05; I2 =
      29.4%; and OR = 1.98; 95%CI = 1.42-2.77; P < 0.05; I2 = 67%, respectively). In
      conclusion, PPI use increased the risk of SBP and overall bacterial infection in
      patients with cirrhosis and ascites. PPIs should be administered after careful
      assessment of the indications in cirrhotic patients. Future well-designed
      prospective studies are warranted to clarify the dose relationships and to
      compare infection risks associated with different classes of PPIs. 

PMID- 26214429
TI  - Genetic diversity, population structure, and association mapping of agronomic
      traits in waxy and normal maize inbred lines.
AB  - Understanding genetic diversity, population structure, and linkage disequilibrium
      is a prerequisite for the association mapping of complex traits in a target
      population. In this study, the genetic diversity and population structure of 40
      waxy and 40 normal inbred maize lines were investigated using 10 morphological
      traits and 200 simple sequence repeat (SSR) markers. Based on a population
      structure analysis, the 80 maize inbred lines were divided into three groups: I,
      II, and admixed. Significant marker-trait associations were identified between
      the markers and the 10 morphological traits, which were studied according to the
      model used to confirm the association. Using a general linear model, the lowest
      R(2) value (9.03) was detected in umc1139, which was associated with ear number,
      and the highest (43.97) was in umc1858, which was associated with plant height.
      Using a mixed linear model, the lowest R(2) value (18.74) was in umc1279, which
      was associated with ear weight; the highest (27.66) was in umc1858, which was
      associated with 100-kernel weight. The SSR markers identified in the present
      study may serve as useful molecular markers for selecting important yield and
      agronomic traits. These results will be useful for marker-assisted selection in
      maize breeding programs, to help breeders choose parental lines and markers for
      crosses.

PMID- 26214430
TI  - Treatment of Moyamoya disease by multipoint skull drilling for indirect
      revascularization combined with mobilization of autologous bone marrow stem
      cells.
AB  - This study discusses the clinical efficacy of multipoint skull drilling for
      indirect revascularization combined with mobilization of autologous bone marrow
      stem cells and use of simvastatin in the treatment of moyamoya disease. Seventy
      eight patients [control group (group A), 39 patients; experimental group (group
      B), 39 patients] with moyamoya disease were selected. Group A underwent indirect
      revascularization, and group B, in addition to indirect revascularization,
      received alternate subcutaneous injections from day 7 post-surgery. The number
      and differentiation of the mobilized bone marrow stem cells were detected by the
      proportion of hematopoietic progenitor cell (HPCs) in mononuclear cells (MNCs) in
      the peripheral blood. There was no statistical difference in the BI (80.2 +/-
      13.7) and NIHSS (6.7 +/- 2.3) scores between the groups before treatment (P >
      0.05). The CSS score of group B was 13.5 +/- 0.6 and there was a statistical
      significance compared to group A (18.2 +/- 0.8) (P < 0.05). There was no
      statistical difference in the proportion of CD34+ CDl33+ cells in MNCs in
      peripheral blood before surgery between the two groups (P > 0.05) and the
      proportions of CD34+ CDl33+ cells in MNCs in peripheral blood in groups A and B
      at 30 days after surgery were significantly higher than those before surgery (P <
      0.05). Treating moyamoya disease by multipoint skull drilling for indirect
      revascularization combined with mobilization of autologous bone marrow stem cells
      and simvastatin is a safe and effective method as it can promote recovery of
      neurological functions and improve patients' daily living abilities and quality
      of life.

PMID- 26214431
TI  - Propofol suppresses proliferation and invasion of pancreatic cancer cells by
      upregulating microRNA-133a expression.
AB  - Propofol is a commonly used intravenous anesthetic. We evaluated its effects on
      the behavior of human pancreatic cancer cells and the underlying molecular
      mechanisms. The effects of propofol on Panc-1 cell proliferation, apoptosis, and
      invasion were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay, caspase-3 activity measurement, and Matrigel invasion assay.
      Quantitative polymerase chain reaction (qPCR) was used to assess microRNA-133a
      (miR-133a) expression. Anti-miR-133a was transfected into Panc-1 cells to assess
      the role of miR-133a in propofol-induced antitumor activity. Propofol
      significantly inhibited Panc-1 cell proliferation and invasion, and promoted
      apoptosis. Propofol also efficiently elevated miR-133a expression. Moreover,
      transfection of anti-miR-133a reversed the effects of propofol on the biological
      behavior of Panc-1 cells. Propofol can effectively inhibit proliferation and
      invasion, and induce apoptosis of pancreatic cancer cells, at least partly
      through the upregulation of miR-133a expression.

PMID- 26214432
TI  - Effects of 6-week specific low-intensity training on selected aerobic capacity
      parameters and HSPA1A, HSPB1, and LDHb gene expression in high-level rowers.
AB  - The aim of this study was to demonstrate the effects of 6-week low-intensity
      training on changes in indicators of aerobic capacity and on HSPA1A, HSPB1, and
      LDHb expression in white blood cells in high level rowers. We hypothesized that
      the type of training would have an impact not only on the adaptation of athletes
      to the aerobic nature of the exercises, but also on the expression of genes,
      designated during exercises "until refusal". Nine Polish lightweight male rowers
      (21.8 +/- 3.77 years of age, 74.2 +/- 1.7 6 kg, 184.8 +/- 4.58 cm) of high level
      participated in the experiment. To determine the anaerobic threshold (AnT) and
      peak oxygen uptake (VO2max) at the beginning and end of the 6-week training
      period, the subjects performed the test "till exhaustion", with increasing load.
      Directly before and after the test, blood samples were collected from the ulnar
      vein for isolation of RNA. Consecutively, reverse transcription and real time
      polymerase chain reaction amplification was performed. A significant influence of
      applied training on physiological parameters such as VO2max (P = 0.0001), AnT
      (W/AT) (P = 0.0007), and maximal acid lactate concentration (P = 0.018) as well
      as on HSPA1A expression (P = 0.0129) in rowers were detected. The 6-week low
      intensity aerobic training significantly affected the physiological parameters
      and HSPA1A expression in the rowers. Therefore, we suggest that the response of
      leukocytes by activating HSPA1A was dependent on the type of training. The 6-week
      period proved sufficiently long to of adapting leukocytes in athletes to high
      intensity exercises. 

PMID- 26214433
TI  - Inhibitory effects of a dendritic cell vaccine loaded with radiation-induced
      apoptotic tumor cells on tumor cell antigens in mouse bladder cancer.
AB  - Herein, the preparation of a dendritic cell (DC) vaccine with radiation-induced
      apoptotic tumor cells and its immunological effects on bladder cancer in C57BL/6
      mice was investigated. We used radiation to obtain a MB49 cell antigen that was
      sensitive to bone marrow-derived DCs to prepare a DC vaccine. An animal model of
      tumor-bearing mice was established with the MB49 mouse bladder cancer cell line.
      Animals were randomly allocated to an experimental group or control group. DC
      vaccine or phosphate-buffered saline was given 7 days before inoculation with
      tumor cells. Each group consisted of 2 subgroups in which tumor volume and the
      survival of tumor-bearing mice were recorded. Tumor volumes and average tumor
      masses of mice administered DC vaccine loaded with radiation-induced apoptotic
      cells were significantly lower than those in the control group (P < 0.01).
      Survival in the experimental group was also longer than that in the control
      group, and 2 mice survived without tumor formation. In the DC vaccine group, 2
      mice were alive without tumor growth after 30 days, and no tumor was observed at
      30 days after subcutaneous inoculation of MB49 cells. The DC vaccine loaded with
      radiation-induced apoptotic tumor cells had an anti-tumor effect and was
      associated with increased survival in a bladder cancer model in mice. 

PMID- 26214434
TI  - Genetic diversity analysis of tree peony germplasm using iPBS markers.
AB  - We examined the genetic diversity of 10 wild species (populations) and 55
      varieties of tree peony using inter-primer binding site (iPBS) markers. From a
      total of 36 iPBS primers, 16 were selected based on polymorphic amplification.
      The number of bands amplified by each primer ranged from 9 to 19, with an average
      of 12.88 bands per primer. The length of bands ranged from 100 to 2000 bp,
      concentrated at 200 to 1800 bp. Sixteen primers amplified 206 bands in total, of
      which 173 bands were polymorphic with a polymorphism ratio of 83.98%. Each primer
      amplified 10.81 polymorphic bands on average. The data were then used to
      construct a phylogenetic tree using unweighted pair group method with arithmetic
      mean methods. Clustering analysis showed that the genetic relationships among the
      varieties were not only related to the genetic background or geographic origin,
      but also to the flowering phase, flower color, and flower type. Our data also
      indicated that iPBS markers were useful tools for classifying tree peony
      germplasms and for tree peony breeding, and the specific bands were helpful for
      molecular identification of tree peony varieties. 

PMID- 26214435
TI  - Endophytic bacteria from Piper tuberculatum Jacq.: isolation, molecular
      characterization, and in vitro screening for the control of Fusarium solani f. sp
      piperis, the causal agent of root rot disease in black pepper (Piper nigrum L.).
AB  - Endophytic bacteria have been found to colonize internal tissues in many
      different plants, where they can have several beneficial effects, including
      defense against pathogens. In this study, we aimed to identify endophytic
      bacteria associated with roots of the tropical piperaceae Piper tuberculatum,
      which is known for its resistance to infection by Fusarium solani f. sp piperis,
      the causal agent of black pepper (Piper nigrum) root rot disease in the Amazon
      region. Based on 16S rRNA gene sequence analysis, we isolated endophytes
      belonging to 13 genera: Bacillus, Paenibacillus, Pseudomonas, Enterobacter,
      Rhizobium, Sinorhizobium, Agrobacterium, Ralstonia, Serratia, Cupriavidus,
      Mitsuaria, Pantoea, and Staphylococcus. The results showed that 56.52% of
      isolates were associated with the phylum Proteobacteria, which comprised alpha,
      beta, and gamma classes. Other bacteria were related to the phylum Firmicutes,
      including Bacillus, which was the most abundant genus among all isolates.
      Antagonistic assays revealed that Pt12 and Pt13 isolates, identified as
      Pseudomonas putida and Pseudomonas sp, respectively, were able to inhibit F.
      solani f. sp piperis growth in vitro. We describe, for the first time, the
      molecular identification of 23 endophytic bacteria from P. tuberculatum, among
      which two Pseudomonas species have the potential to control the pathogen
      responsible for root rot disease in black pepper in the Amazon region. 

PMID- 26214436
TI  - Development of expressed sequence tag-simple sequence repeat markers for
      Chrysanthemum morifolium and closely related species.
AB  - With the development of chrysanthemum breeding in recent years, an increasing
      number of wild species in genera related to Chrysanthemum were introduced to
      extend the genetic resources and facilitate the genetic improvement of
      chrysanthemums via hybridization. However, few simple sequence repeat (SSR)
      markers are available for marker-assisted breeding and population genetic studies
      of chrysanthemum and closely related species. Expressed sequence tags (ESTs) in
      public databases and cross-species transferable markers are considered to be a
      cost-effective means for developing sequence-based markers. In this study, 25 EST
      SSRs were successfully developed from Chrysanthemum EST sequences for
      Chrysanthemum morifolium and closely related species. In total, 4164 unigene
      sequences were assembled from 7180 ESTs of chrysanthemum in GenBank, which were
      subsequently used to screen for the presence of microsatellites with the SSRIT
      software. The screening criteria were 8, 5, 4, and 3 repeating units for di-, tri
      , tetra-, and penta- and higher-order nucleotides, respectively. Moreover, 310
      SSR loci from 296 sequences were identified, and 198 primer pairs for SSR
      amplification were designed with the Primer Premier 5.0 software, of which 25 SSR
      loci showed polymorphic amplification in 52 species and varieties belonging to
      Chrysanthemum, Ajania, and Opisthopappus. The application of EST-SSR markers to
      the identification of intergeneric hybrids between Chrysanthemum and Ajania was
      demonstrated. Therefore, EST-SSRs can be developed for species that lack gene
      sequences or ESTs by utilizing ESTs of closely related species. 

PMID- 26214437
TI  - Genetic diversity in Tunisian populations of faba bean (Vicia faba L.) based on
      morphological traits and molecular markers.
AB  - Genetic diversity within Vicia faba L. is key to the genetic improvement of this
      important species. In this study, morphological traits and RAPD molecular markers
      were used to assess the levels of polymorphism across 12 Tunisian populations,
      three major and nine minor from different locations. Analysis of morphological
      traits indicated that the three major populations showed significant differences
      and the nine minor populations exhibited considerable variation for most traits.
      The grain yield of the Alia population could be increased by inoculation. Of the
      seven primers tested, it was clear that the Cs12 primer would be recommend for
      genetic diversity analysis of V. faba.Within population genetic diversity
      exhibited 94% of total diversity. Intra-population genetic diversity (HS) was
      0.16, which was clearly higher than between population genetic diversity (DST =
      0.06) UPG-MA showed a high level of genetic variation between major and minor
      populations of V. faba L. Particularly the minor populations showed a high level
      of diversity and was divided into two subclusters. Ltaifia was separated from the
      other populations. In addition to a high grain yield, these populations showed
      the lowest Nei and Shannon indices (H = 0.08 and I = 0.13) justifying their
      homogeneity. For these reasons, these cultivars can be considered a selected
      population. However, the Takelsa population showed the highest Nei and Shannon
      indices (H = 0.13 and I = 0.21), indicating that this population was the most
      heterogeneous, which is interesting for breeding programs.

PMID- 26214438
TI  - Bispectral index for monitoring anesthetic depth in patients with severe burns
      receiving target-controlled infusion of remifentanil and propofol.
AB  - This study evaluated the feasibility and effectiveness of using the bispectral
      index (BIS) to monitor anesthetic depth in patients with severe burns receiving
      intravenous target-controlled infusion (TCI) of remifentanil and propofol. We
      randomly assigned 80 patients undergoing elective escharectomy (<1 week) to BIS
      (A) and control (B) groups. All patients received remifentanil and propofol as
      intravenous TCI anesthesia. Clinical data were recorded at different time points.
      The time from drug withdrawal to eye opening upon the patient hearing his/her
      name called and upon reaching an Aldrete score of 9 points was also recorded.
      During anesthesia maintenance, the target concentrations of remifentanil and
      propofol in group A were significantly lower than that in group B (2.12 +/- 0.35
      vs 2.50 +/- 0.21 ng/mL and 2.54 +/- 0.22 vs 2.86 +/- 0.31 MUg/mL, respectively; P
      < 0.01). The time from drug withdrawal to eye opening upon the patient hearing
      his/her name called and reaching an Aldrete score of 9 points in group A was
      considerably shorter than that in group B (7.90 +/- 0.58 vs 8.35 +/- 0.66 min and
      9.15 +/- 0.69 vs 11.13 +/- 0.96 min, respectively; P < 0.01). In both groups,
      mean arterial pressure and heart rate values at each time point after loss of
      consciousness were significantly lower than the baseline values (P < 0.05), with
      the exception of 2 min after intubation. The use of BIS to monitor anesthetic
      depth in patients with severe burns receiving TCI of remifentanil and propofol
      during the perioperative period reduces propofol consumption and shortens the
      consciousness recovery time in patients.

PMID- 26214439
TI  - Synergistic effect of BMP9 and TGF-beta in the proliferation and differentiation
      of osteoblasts.
AB  - We investigated the synergistic effect of bone morphogenetic protein 9 (BMP9) and
      transforming growth factor (TGF)-b in the transformation of mesenchymal stem
      cells into osteoblasts. We evaluated the effect of BMP9 and TGF-b on the
      induction of osteoblast formation. Mitogen-activated protein kinase (MAPK)
      pathway-related proteins such as p38, extracellular receptor kinase 1/2, and c
      Jun N-terminal kinase (JNK) were analyzed. The interactions between TGF-Smad and
      BMP-MAPK were also studied. BMP9 alone induced the differentiation of mesenchymal
      stem cells (MSCs) into osteoblasts and enhanced phosphorylation of p38,
      extracellular receptor kinase 1/2, and JNK. TGF-b alone failed to induce
      transformation, but could increase the effect of BMP9. In this process the
      activation of Smad resulted in activation of the JNK pathway in the MAPK pathway.
      BMP9 induced osteogenesis of MSC differentiation through the MAKP pathway, while
      TGF-b contributed to BMP9 enhancement through the Smad-JNK pathway.

PMID- 26214440
TI  - Radiofrequency thermocoagulation combined with pulsed radiofrequency helps
      relieve postoperative complications of trigeminal neuralgia.
AB  - Trigeminal neuralgia is a sudden, severe condition characterized by stabbing and
      recurrent pain. Radiofrequency thermocoagulation (RFT) and pulsed radiofrequency
      (PRF) are common surgical interventions used to treat trigeminal neuralgia. This
      study aimed to investigate the therapeutic effects and associated complications
      of a combination of RFT and PRF in the treatment of trigeminal neuralgia.
      Computed tomography-guided percutaneous RFT of the Gasserian ganglion was
      performed on 80 patients with trigeminal neuralgia. Patients were randomly
      assigned to either group A (RFT at 70 degrees C) or group B (RFT at 75 degrees
      C). Patients in each group were divided into 2 subgroups, receiving percutaneous
      RFT (240 s) with or without PRF (42 degrees C, 2 Hz, 240 s). Six months later,
      pain relief and complication status were evaluated. There was no significant
      difference in visual analogue scores among groups with RFT at 70 degrees  or 75
      degrees C, with or without PRF. Data showed that facial numbness and
      postoperative masticatory muscle weakness recovered more rapidly in patients
      receiving combined RFT and PRF treatment. Decreased corneal reflex was relieved
      to a significantly greater extent in groups receiving PRF than those without.
      Thus, compared to the use of RFT at 75 degrees C alone, the combination of PRF
      and RFT helped eliminate postoperative complications, such as facial numbness,
      masticatory muscle weakness, and decreased corneal reflex, indicating that it
      could be useful for surgically treating trigeminal neuralgia.

PMID- 26214441
TI  - Expression changes in epithelial cell adhesion molecule during colorectal cancer
      tumorigenesis.
AB  - We investigated the relationship between the expression of epithelial cell
      adhesion molecule (EpCAM) and the occurrence and development of colon cancer.
      Fifty colon cancer tissues and adjacent normal tissues were collected, while 40
      normal intestinal mucosa tissues were collected as the blank group. EpCAM
      expression was detected by immunohistochemistry and the patients were followed-up
      to evaluate the prognosis. The positive expression rate of EpCAM reached 93.7% in
      patients with colorectal carcinoma, which was significantly higher than that in
      the negative control group and blank group (14.8 and 12.7%, P < 0.05,
      respectively). There was no significant difference between the control group and
      blank group regarding EpCAM expression. No direct relationship was observed
      between EpCAM expression and patient age, gender, and other characteristics.
      EpCAM was overexpressed in colorectal cancer and had a high detection rate. EpCAM
      can be used as a diagnostic biomarker for clinical detection of colorectal
      cancer. 

PMID- 26214442
TI  - Isolation and characterization of microsatellite loci in the purpleback flying
      squid (Sthenoteuthis oualaniensi).
AB  - The purpleback flying squid (Sthenoteuthis oualaniensis) is a pelagic squid with
      tremendous potential for commercial exploitation. We isolated and characterized
      21 polymorphic microsatellite loci for S. oualaniensis using a (GT)13-enriched
      genomic library. The number of alleles per locus varied from 6 to 32. The
      observed and expected heterozygosities ranged from 0.188 to 0.890, and 0.537 to
      0.968, respectively. No significant linkage disequilibrium was detected at these
      loci. Five loci significantly deviated from the Hardy-Weinberg equilibrium, and
      four loci may have exhibited null alleles. These microsatellite markers will
      facilitate further studies in population genetics and the sustainable utilization
      of S. oualaniensis. 

PMID- 26214443
TI  - Predictive value of vascular endothelial growth factor polymorphisms on the risk
      of renal cell carcinomas.
AB  - We conducted a case-control study in a Chinese population to assess whether 5
      common single-nucleotide polymorphisms in the vascular endothelial growth factor
      gene (VEGF) affect the risk of renal cell carcinoma (RCC). The study population
      included 266 RCC patients who were newly diagnosed and histologically confirmed
      to have RCC as well as 532 cancer-free controls. Genotyping of VEGF -2578C/A, 
      1156G/A, +1612G/A, +936C/T, and -634G/C was conducted by polymerase chain
      reaction-restriction fragment length polymorphism. RCC patients were more likely
      to have higher body mass index, and have a habit of tobacco smoking as well as
      suffer from diabetes. Conditional logistic regression analyses showed that
      individuals with the AA genotype and A allele of -2578C/A significantly increased
      the risk of RCC when compared with the CC genotype. Individuals carrying the CT
      and TT geno-types of +936C/T were correlated with an increased risk of RCC
      compared to the CC genotype. The T allele of +936C/T was associated with an
      increased risk of RCC. The -2578C/A and +936C/T polymorphisms in the VEGF gene
      may play a role in the etiology of RCC.

PMID- 26214444
TI  - Branches of NF-kappab signaling pathway regulate hepatocyte proliferation in rat
      liver regeneration.
AB  - Previous studies have demonstrated that the nuclear factor kappaB (NF-kappaB)
      pathway is involved in promoting cell proliferation. To further explore the
      regulatory branches and their sequence in the NF-kappaB pathway in the promotion
      of hepatocyte proliferation at the transcriptional level during rat liver
      regeneration, Rat Genome 230 2.0 array was used to detect the expression changes
      of the isolated hepatocytes. We found that many genes involved in the NF-kappaB
      pathway (including 73 known genes and 19 homologous genes) and cell proliferation
      (including 484 genes and 104 homologous genes) were associated with liver
      regeneration. Expression profile function (Ep) was used to analyze the biological
      processes. It was revealed that the NF-kappaB pathway promoted hepatocyte
      proliferation through three branches. Several methods of integrated statistics
      were applied to extract and screen key genes in liver regeneration, and it
      indicated that eight genes may play a vital role in rat liver regeneration. To
      confirm the above predicted results, Ccnd1, Jun and Myc were analyzed using qRT
      PCR, and the results were generally consistent with that of microarray data. It
      is concluded that 3 branches and 8 key genes involved in the NF-kappaB pathway
      regulate hepatocyte proliferation during rat liver regeneration. 

PMID- 26214445
TI  - Association between polymorphisms in insulin-like growth factor-1 and risk of
      osteoporosis.
AB  - We conducted a case-control study to assess the relation-ship between rs35767,
      rs2288377, and rs5742612 insulin-like growth factor-1 (IGF-1) and osteoporosis
      risk in a Chinese female population. The genotypes of rs35767, rs2288377, and
      rs5742612 of IGF-1 were determined by polymerase chain reaction-restriction
      fragment length polymorphism. Patients with osteoporosis were more likely to have
      drinking and smoking habits and have lower bone mineral density in the L2-L4
      vertebrae, femoral neck, and total hip. According to conditional regression
      analysis, individuals carrying the TT genotype of rs35767 had an increased risk
      of osteoporosis, with an adjusted odds ratio (95% confidence interval) of 2.29
      (1.35-4.97). In conclusion, our results sug-gest that the TT genotype of IGF-I
      rs35767 was associated with an in-creased risk of osteoporosis, suggesting that
      this polymorphism can be used as a predictive factor for osteoporosis risk. 

PMID- 26214446
TI  - Purification of the insecticidal Cry2Ad protein from a Bt-isolated BRC-HZP10
      strain and toxin assay to the diamondback moth, Plutella xylostella (L.).
AB  - The present study aims to characterize the Cry2Ad toxin protein isolated from a
      Bacillus thuringiensis strain, BRC-HZP10, which have a potential insecticidal
      activity against larvae of the diamondback moth, Plutella xylostella (L.). The
      crude Bt toxin proteins were isolated and purified by cation exchange
      chromatography, then equilibrated with 0.2 M NaOH buffer, pH 4.0, followed by
      ultraviolet detection at 280 nm and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. A refined Cry2Ad toxin protein with 88.34% purity was eventually
      obtained and used for a bioassay by feeding it to P. xylostella. The results
      showed conspicuous insecticidal activity towards P. xylostella with 50% lethal
      concentration of 6.84 MUg/mL and 95% confidence interval of 5.77-7.91 mg/mL. At a
      concentration of 16.38 MUg/mL, the intake of Cry2Ad protein significantly
      shortened the oviposition period and larval developmental duration, but
      significantly reduced the fecundity and egg hatchability of the population
      compared to those of control (without treatment with Cry2Ad protein) (P < 0.05).
      These results indicate that the Cry2Ad protein plays an effective role in
      controlling the population of P. xylostella. 

PMID- 26214447
TI  - Fructus polygoni orentalis extract inhibited liver regeneration and proliferation
      of bone marrow cells of rat after partial hepatectomy.
AB  - To study the effect of fructus polygoni orentalis extract (EFPO) on liver
      regeneration and proliferation of bone marrow cells on rat model of partial
      hepatectomy, EFPO was extracted, and 60 adult male Wistar rats were divided
      randomly into 6 experimental groups. Rats were treated with intergastric
      administration (ig) with EFPO daily. All rats were euthanized 7 days after
      administration, and the livers and bone marrow cells were collected. The levels
      of taxifolin and quercetin in EFPO were 1.238 and 0.381 mg/g, respectively. EFPO
      decreased the proliferating cell nuclear antigen expression of the regenerating
      liver. Obvious tissue damage was observed in the EFPO groups, such as a widened
      hepatic sinusoid cavity, several enlarged nuclei, slightly ballooning
      degeneration, and spotty and focal necrosis as compared to the control group.
      Additionally, 1.8 and 3.6 g/kg EFPO significantly inhibited proliferating cell
      nuclear antigen expression in bone marrows cells (P < 0.05), and induced
      gathering of these cells during the GO/G1 phases (P < 0.05). The karyocyte and
      myelosis of bone marrows cells clearly decreased, and mature erythrocytes
      increased (P < 0.05) in the EFPO groups. Additionally, 3.6 g/kg EFPO induced
      active proliferation, while the sham operation and control groups showed apparent
      active myelo-proliferation. The maximum dosage of mice ig EFPO was 148.8 g/kg.
      Our results indicate that EFPO inhibits rat liver regeneration and bone marrow
      cell proliferation in regenerating rat liver.

PMID- 26214448
TI  - Association between the hsa-miR-146a rs2910164 functional polymorphism with
      susceptibility to intracranial aneurysm.
AB  - Vascular inflammation has been shown to be involved in the pathogenesis of
      intracranial aneurysms (IA). MiRNAs are key molecules that participate in the
      regulation of many important biological processes including inflammation. Studies
      on the hsa-miR-146a rs2910164 polymorphism and its association with different
      inflammatory related diseases have engendered inconsistent results, and until
      now, there have been no reports on the association between this polymorphism and
      the susceptibility to IA. In this study, we aimed to investigate whether the
      rs2910164 polymorphism is involved in the process of IA. We genotyped 164
      patients with IA and 478 healthy controls using a polymerase chain reaction
      restriction fragment length polymorphism assay. All subjects were Chinese. The
      distributions of rs2910164 genotypes and alleles between patients with IA and
      healthy controls were similar [CG vs CC: odds ratio (OR) = 0.701, 95% confidence
      interval (CI) = 0.456-1.080; GG vs CC: OR = 0.920, 95%CI = 0.524-1.617; G vs C:
      OR = 0.939, 95%CI = 0.731-1.208, respectively]. No association was found between
      the hsa-miR-146a rs2910164 polymorphism and the risk of IA in the analyzed
      population. 

PMID- 26214449
TI  - Accumulation of flavanols and expression of leucoanthocyanidin reductase induced
      by postharvest UV-C irradiation in grape berry.
AB  - To examine the effect of postharvest ultraviolet C (UV-C) irradiation on flavanol
      polyphenol accumulation in the grape berry, we investigated total flavanol
      polyphenol content, the enzyme activity of leucoanthocyanidin reductase (LAR),
      and transcription of Vv lar1 and Vv lar2 using spectrophotometry, real-time
      polymerase chain reaction, and western blot analysis in 5-year-old Vitis vinifera
      L. cv. Cabernet Sauvignon plants. Our results indicated that the accumulation of
      flavanol polyphenol reached its highest value when exposed to UV-C irradiation
      for 30 min. Additionally, UV-C irradiation induced the transcription of Vv lar1
      and Vv lar2 and the synthesis of LAR1 and LAR2 proteins, resulting in increased
      accumulation of flavanol polyphenol in the grape berry. Moreover, these effects
      were associated with the length of time of UV-C irradiation. 

PMID- 26214450
TI  - Neuroprotective effects of Bcl-2 overexpression on nerve cells of rats with acute
      cerebral infarction.
AB  - We aimed to investigate the influence of lentiviral-mediated Bcl-2 overexpression
      in cerebral tissues of rats with acute cerebral infarction. Forty-five rats were
      randomly divided into sham, model, and treatment groups. The sham and model
      groups were administered a control lentiviral vector via the intracranial
      arteries 10 days before surgery, while the treatment group received lentivirus
      encoding a Bcl-2 overexpression vector. We induced cerebral artery infarction
      using a suture-occlusion method and analyzed the cerebral expression levels of
      apoptosis-related genes (caspase-3, Bax), total cerebral apoptosis, range of
      cerebral tissue infarction, and changes in nerve cell function after 72 h. The
      Bcl-2-encoding lentivirus was well expressed in rat cerebral tissues. The
      treatment group had significantly higher expression levels of Bcl-2 than the
      other two groups. After cerebral infarction, the model group had significantly
      increased expression levels of caspase-3 and Bax protein in cerebral tissues than
      the sham (P < 0.05). Expression of these apoptosis-related proteins in the
      treatment group was obviously lower than that in the model group (P < 0.05), but
      significantly higher than in the sham group (P < 0.05). Compared to sham,
      neuronal apoptosis levels and infarction range of cerebral tissues was increased
      in the model and treatment groups; however, these values in the treatment group
      were significantly lower than that in the model group (P < 0.05). Importantly,
      the treatment group had significantly decreased neurological impairment scores (P
      < 0.05). In conclusion, Bcl-2 over-expression can decrease neuronal apoptosis in
      rat cerebral tissue, and thus is neuroprotective after cerebral ischemia.

PMID- 26214451
TI  - Effects of sex and age on chicken TBC1D1 gene mRNA expression.
AB  - The objective of this study was to investigate the effects of sex and slaughter
      age of chickens on fatty acid composition and TBC1D1 gene expression in 4
      different tissues: breast muscle, thigh muscle, abdominal fat, and subcutaneous
      fat. Sixty Erlang mountainous chickens (hybrid SD02 x SD03) were raised under the
      same conditions and slaughtered at 8, 10, and 13 weeks of age. The results showed
      that the sex of the animal significantly affected the content of arachidic acid
      (C20:0), sinapic (C22:1), linoleic (C18:2n-6), eicosapentaenoic (C20:5n-3), and
      docosahexaenoic acids (C22:6n-3), whereas other fatty acid contents were not
      affected. Age had a significant effect on most monounsaturated fatty acids,
      except for octadecenoic acid (C18:1). TBC1D1 mRNA was abundant in all tissues at
      all 3 ages of slaughter. Cocks exhibited higher TBC1D1 mRNA levels than hens in
      the thigh muscle and abdominal fat at 10 and 13 weeks, respectively. 

PMID- 26214452
TI  - Development of novel chloroplast microsatellite markers for Ginkgo biloba.
AB  - Ginkgo biloba is considered to be a living fossil that can be used to understand
      the ancient evolutionary history of gymnosperms, but little attention has been
      given to the study of its population genetics, molecular phylogeography, and
      genetic resources assessment. Chloroplast simple sequence repeat (cpSSR) markers
      are powerful tools for genetic studies of plants. In this study, a total of 30
      perfect cpSSRs of Ginkgo were identified and characterized, including di-, tri,
      tetra-, penta-, and hexanucleotide repeats. Fifteen of 21 designed primer pairs
      were successfully amplified to yield specific polymerase chain reaction products
      from 16 Ginkgo cultivars. Polymorphic cpSSRs were further applied to determine
      the genetic variation of 116 individuals in 5 populations of G. biloba. The
      results showed that 24 and 76% genetic variation existed within and among
      populations of this species, respectively. These polymorphic and monomorphic
      cpSSR markers can be used to trace the origin and evolutionary history of Ginkgo.

PMID- 26214453
TI  - Stimulation of bacterial biofilms on Th17 immune cells.
AB  - We investigated the role of bacterial biofilms in stimulating T helper 17 (Th17)
      cells in infected organisms. The formation of bacterial biofilms isolated from
      clinical lavage fluid samples was measured. Th17 cells and interleukin 17 (IL-17)
      levels in the peripheral blood of healthy individuals, people infected by biofilm
      bacteria, people infected by non-biofilm bacteria, and in the lavage fluid from
      people infected by bacteria were determined. Differences in those data were
      tested using the SPSS 17.0 statistical software. Th17 cells and IL-17 levels in
      the peripheral blood of biofilm bacteria-infected people, non-biofilm bacteria
      infected people, and healthy controls were 0.59 +/- 0.18% and 108.8 +/- 20.5
      pg/mL; 0.58 +/- 0.18% and 100.1 +/- 20.7 pg/mL; and 0.55 +/- 0.17% and 100.0 +/-
      21.4 pg/mL, respectively; there were no statistically significant differences (P
      > 0.05). Th17 cells and IL-17 levels in the lavage fluid of biofilm bacteria
      infected people and non-biofilm bacteria-infected people were 1.37 +/- 0.34% and
      157.4 +/- 30.8 pg/mL; and 1.11 +/- 0.21% and 136.2 +/- 24.3 mg/mL, respectively;
      the differences were statistically significant (P < 0.05). Bacterial biofilms can
      increase the expression levels of Th17 cells and IL-17 in local infections; this
      may be the mechanism by which chronic injuries are caused by biofilm infections. 

PMID- 26214454
TI  - Genetic diversity of the endemic flat-needle pine Pinus krempfii (Pinaceae) from
      Vietnam revealed by SSR markers.
AB  - Pinus krempfii Lecomte (Pinaceae) is an endemic tree to Vietnam with restricted
      habitats at higher altitudes in the highlands. In this study, genetic variation
      of four populations of P. krempfii was assessed using 17 microsatellite markers
      (single sequence repeats). Of these 17 markers, eight were polymorphic, and among
      the 42 putative alleles amplified, 32 were polymorphic (accounting for 76.19%).
      The Cong Troi population was found to be the most genetically diverse (Shannon's
      information index, I = 0.415, and percentage of polymorphic bands, PPB = 52.95%),
      whereas the Hon Giao population was found to have the lowest diversity (I = 0.330
      and PPB = 47.06%). The genetic diversity at species level was also estimated (I =
      0.414, PPB = 76.19%). Molecular variance was found to be low among populations
      (11.94%) and high among individuals within the populations (88.06%). Private
      alleles were not detected in the Hon Giao population. The Yang Ly population had
      a positive FIS (inbreeding coefficient) value of 0.071, while the three remaining
      populations had negative values (-0.116 for Cong Troi, -0.316 for Chu Yang Sin,
      and -0.350 for Hon Giao). The results obtained show an excess of homozygosity in
      the Yang Ly population, and also suggest a deficiency of heterozygosity for this
      population. Several approaches and measures of conservation for P. krempfii are
      discussed and proposed. 

PMID- 26214455
TI  - Molecular cloning, characterization, and expression of Rab5B, Rab6A, and Rab7
      from Litopenaeus vannamei (Penaeidae).
AB  - The Rab protein family belongs to a superfamily of ras-like GTP-binding proteins.
      Rab proteins regulate many steps of membrane trafficking. In this study, three
      Rab family members, Rab5B, Rab6A, and Rab7, designated LvRab5B, LvRab6A, and
      LvRab7, were cloned from Litopenaeus vannamei. The full-length cDNA sequences of
      LvRab5B, LvRab6A, and LvRab7 were 1383, 873, and 767 nucleotides in length and
      they encoded proteins of 211, 212, and 205 amino acids, respectively. Using qRT
      PCR, the mRNA expression levels of the three proteins were determined in the
      hepatopancreas of L. vannamei at different stages after infectious hypodermal and
      hematopoietic necrosis virus and white spot syndrome virus challenge. The results
      indicated that the mRNA expression levels of LvRab5B, LvRab6A, and LvRab7 were
      all significantly up-regulated after virus injection, suggesting that these genes
      may play essential roles in the immune response to viral infection in shrimp. 

PMID- 26214456
TI  - Relationship between a lipoprotein lipase gene polymorphism in placental tissue
      and insulin resistance in patients with gestational diabetes mellitus.
AB  - The aim of this study was to investigate the relationship between a lipoprotein
      lipase (LPL) gene polymorphism in placental tissue and insulin resistance (IR) in
      patients with gestational diabetes mellitus. Using polymerase chain reaction
      restriction enzyme fragment length polymorphism (PCR-RFLP) analysis, the LPL
      HindIII RFLP was examined in the placental tissue of 110 patients with
      gestational diabetes mellitus (observation group) and 110 women with normal
      gestation (control group). The relationships between fasting plasma glucose
      (FPG), postprandial plasma glucose (PPG), fasting insulin (FINS), cholesterol
      (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein
      (LDL), body mass index (BMI), and IR indices and the LPL polymorphism in the two
      study groups and their offspring were determined. The frequency of the H+ allele
      was significantly higher in the observation group than in the controls (P <
      0.05). There were statistically significant differences in the observation group
      between the FPG, PPG, LDL, TC, TG, HDL, BMI, FINS, and IR indices of the H+H+
      group and those of the non H+H+ type patients (P < 0.05). Correlation analysis
      showed that the LPL gene polymorphism was positively related to IR. There were
      statistically significant differences between HDL, BMI, and IR indices between
      the two study groups (P < 0.05). In conclusion, the LPL gene polymorphism was
      determined to be the main factor related to IR in women with gestational
      diabetes, and was also found to be related to the IR of their offspring. 

PMID- 26214457
TI  - Genetic fidelity and variability of micropropagated cassava plants (Manihot
      esculenta Crantz) evaluated using ISSR markers.
AB  - Molecular markers are efficient for assessing the genetic fidelity of various
      species of plants after in vitro culture. In this study, we evaluated the genetic
      fidelity and variability of micropropagated cassava plants (Manihot esculenta
      Crantz) using inter-simple sequence repeat markers. Twenty-two cassava accessions
      from the Embrapa Cassava & Fruits Germplasm Bank were used. For each accession,
      DNA was extracted from a plant maintained in the field and from 3 plants grown in
      vitro. For DNA amplification, 27 inter-simple sequence repeat primers were used,
      of which 24 generated 175 bands; 100 of those bands were polymorphic and were
      used to study genetic variability among accessions of cassava plants maintained
      in the field. Based on the genetic distance matrix calculated using the
      arithmetic complement of the Jaccard's index, genotypes were clustered using the
      unweighted pair group method using arithmetic averages. The number of bands per
      primer was 2-13, with an average of 7.3. For most micropropagated accessions, the
      fidelity study showed no genetic variation between plants of the same accessions
      maintained in the field and those maintained in vitro, confirming the high
      genetic fidelity of the micropropagated plants. However, genetic variability was
      observed among different accessions grown in the field, and clustering based on
      the dissimilarity matrix revealed 7 groups. Inter-simple sequence repeat markers
      were efficient for detecting the genetic homogeneity of cassava plants derived
      from meristem culture, demonstrating the reliability of this propagation system. 

PMID- 26214458
TI  - An improved K-means clustering method for cDNA microarray image segmentation.
AB  - Microarray technology is a powerful tool for human genetic research and other
      biomedical applications. Numerous improvements to the standard K-means algorithm
      have been carried out to complete the image segmentation step. However, most of
      the previous studies classify the image into two clusters. In this paper, we
      propose a novel K-means algorithm, which first classifies the image into three
      clusters, and then one of the three clusters is divided as the background region
      and the other two clusters, as the foreground region. The proposed method was
      evaluated on six different data sets. The analyses of accuracy, efficiency,
      expression values, special gene spots, and noise images demonstrate the
      effectiveness of our method in improving the segmentation quality. 

PMID- 26214459
TI  - A new method to induce myasthenia gravis models and the protective effect of
      soluble decay accelerating factors.
AB  - It is expensive to induce experimental autoimmune myasthenia gravis (EAMG) by
      active immunity, and difficult to obtain natural acetylcholine receptor (AChR).
      We sought a new method of inducing EAMG by immunizing rats with artificially
      synthesized AChR. The AChR mRNA in TE671 cells was extracted and reverse
      transcribed. The inclusion body was purified and protein concentration was
      determined, and the EAMG animal model was used for induction. The serum was
      extracted from rat blood. The antibody titer was determined using enzyme-linked
      immunosorbant assay (ELISA). The concentration of decay accelerating factor (DAF)
      in the rat serum was determined by ELISA, and the metabolism of serum rDAF was
      determined by western blot. We evaluated the inhibition of rDAF by determining
      the 50% complement hemolysis unit in the rat serum. The extracellular domain
      (ECD) nucleotide sequence clone produced by polymerase chain reaction was
      completely consistent with that in the human gene bank; it was induced by
      isopropyl beta-D-1-thiogalactopyranoside to express the protein after insertion
      into vector pET16b. Sodium dodecyl sulfate polyacrylamide gel electrophoresis
      demonstrated that the inclusion body protein was the exact target. The ECD
      protein was able to bind with mAb35 after dialysis and renaturation, which
      demonstrated protein activity. The soluble ECD protein was used to immunize rats
      and obtain the EAMG models. The inhibitory effect of the complement was
      unsatisfactory owing to high decay rate after rDAF injection into the EAMG
      models. It is easy to induce the EAMG model by obtaining the AChRTEalpha1 subunit
      ECD protein using the substitution method. 

PMID- 26214460
TI  - Large-scale detection and application of expressed sequence tag single nucleotide
      polymorphisms in Nicotiana.
AB  - Single nucleotide polymorphisms (SNPs) are widespread in the Nicotiana genome.
      Using an alignment and variation detection method, we developed 20,607,973 SNPs,
      based on the expressed sequence tag sequences of 10 Nicotiana species. The
      replacement rate was much higher than the transversion rate in the SNPs, and SNPs
      widely exist in the Nicotiana. In vitro verification indicated that all of the
      SNPs were high quality and accurate. Evolutionary relationships between 15
      varieties were investigated by polymerase chain reaction with a special primer;
      the specific 302 locus of these sequence results clearly indicated the origin of
      Zhongyan 100. A database of Nicotiana SNPs (NSNP) was developed to store and
      search for SNPs in Nicotiana. NSNP is a tool for researchers to develop SNP
      markers of sequence data. 

PMID- 26214461
TI  - Effect of GBOT on blood lipid and blood glucose metabolism in rats with
      atherosclerosis.
AB  - We observed the variation in in vivo blood lipid and blood glucose metabolism in
      rats with atherosclerosis after 5-(3,4-dihydroxy-phenyl)-1-piperidin-1-yl-penta
      2,4-dien-1-one (GBOT) administration. Wistar rats aged 10 weeks received a high
      fat diet to establish the atherosclerosis model. Metabolic indices related to
      blood lipid and blood glucose were measured before modeling and at 4 and 8 weeks
      after modeling. Liver fat levels in rats were measured at 8 weeks to analyze the
      relationship between liver fat and blood lipid levels. We examined the mechanism
      of blood lipid reduction. The levels of serum triglycerides, total cholesterol,
      and very-low-density lipoprotein cholesterol in rats in the control group were
      significantly decreased (P < 0.05) compared with those in the 4-week control
      group at 4 weeks and decreased significantly and continuously until the 8th week
      (P < 0.05). Compared with the 8-week control group, the blood glucose level in
      rats in the 8-week experimental group decreased significantly (P < 0.05), and the
      level of insulin sensitivity index decreased significantly (P < 0.05). Compared
      with the control group, triglyceride and total cholesterol levels per unit mass
      in rat liver tissue in the 8-week experimental group decreased significantly (P <
      0.05). Western blotting indicated that GBOT significantly increased the
      expression of lecithin-cholesterol acyltransferase, low-density lipoprotein
      receptor, and cholesterol 7 alpha-hydroxylase proteins. GBOT can significantly
      decrease the levels of blood lipid and blood glucose in rat models of
      atherosclerosis, and its mechanism may be associated with the promotion of
      expression of lecithin-cholesterol acyltransferase, low-density lipoprotein
      receptor, and cholesterol 7 alpha-hydroxylase proteins. 

PMID- 26214462
TI  - Comprehensive identification and expression analysis of Hsp90s gene family in
      Solanum lycopersicum.
AB  - Heat shock protein 90 (Hsp90) is a protein produced by plants in response to
      adverse environmental stresses. In this study, we identified and analyzed Hsp90
      gene family members using a bioinformatic method based on genomic data from
      tomato (Solanum lycopersicum L.). The results illustrated that tomato contains at
      least 7 Hsp90 genes distributed on 6 chromosomes; protein lengths ranged from 267
      794 amino acids. Intron numbers ranged from 2-19 in the genes. The phylogenetic
      tree revealed that Hsp90 genes in tomato (Solanum lycopersicum L.), rice (Oryza
      sativa L.), and Arabidopsis (Arabidopsis thaliana L.) could be divided into 5
      groups, which included 3 pairs of orthologous genes and 4 pairs of paralogous
      genes. Expression analysis of RNA-sequence data showed that the Hsp90-1 gene was
      specifically expressed in mature fruits, while Hsp90-5 and Hsp90-6 showed
      opposite expression patterns in various tissues of cultivated and wild tomatoes.
      The expression levels of the Hsp90-1, Hsp90-2, and Hsp90- 3 genes in various
      tissues of cultivated tomatoes were high, while both the expression levels of
      genes Hsp90-3 and Hsp90-4 were low. Additionally, quantitative real-time
      polymerase chain reaction showed that these genes were involved in the responses
      to yellow leaf curl virus in tomato plant leaves. Our results provide a
      foundation for identifying the function of the Hsp90 gene in tomato.

PMID- 26214463
TI  - An expression profiling analysis of hybrid millet and its parents at grain
      filling stage.
AB  - Heterosis has been widely used in crop breeding and production. However, a
      shortage of genes known to function in heterosis significantly limits our
      understanding of the molecular basis underlying heterosis. Here, we report 740
      differentially expressed genes (DEGs) in the leaves of the hybrid millet Zhang
      No.5 and its parents at the grain filling stage determined using Solexa Illumina
      digital gene expression. Of the 740 DEGs, 546 were from the hybrid and its
      parents and most were up-regulated in the hybrid. Particularly, a large number of
      DEGs related to starch and carbohydrate metabolism and 2 DEGs encoding
      chlorophyll a/b binding proteins were up-regulated in hybrid millet. Moreover,
      all DEGs were enriched in the biological process and molecular function, and no
      DEGs were found to be enriched in the cellular component of GO terms. Pathway
      enrichment using KEGG showed that several DEGs were enriched in the circadian
      rhythm pathway. Further analysis revealed that the altered circadian rhythm,
      which mediates photosynthesis and carbohydrate accumulation, may play an
      important role in heterosis of the hybrid millet. 

PMID- 26214464
TI  - Replication timing regulation in adults with chromosomal balance rearrangements.
AB  - The alternative forms of the alleles in biallelic genes display a synchronous
      pattern of replication that is different from genes subjected to monoallelic
      expression, which exhibit an asynchronous mode of replication. The present study
      sought to gain insight into changes in the allele-specific replication timing in
      phenotypically normal humans with balanced chromosomal rearrangements, and to
      investigate the potential mechanism for chromosomal rearrangements. We used
      fluorescence in situ hybridization and chose biallelic gene expression of RB1 and
      monoallelic expression of SNRPN in phytohemagglutinin-stimulated lymphocytes to
      compare differences in the allelic replication timing. We found that compared to
      genetically normal adult controls, adults with a normal phenotype despite
      chromosomal rearrangements showed normal replication timing (synchronous or
      asynchronous) for the RB1 gene and SNRPN genes. Our data support a link between
      chromosomal aberrations and epigenetic stability in phenotypically normal humans,
      independent of the breakpoints in chromosomal structural disruption, and
      represent an epigenetic mark for allelic exclusion in balanced chromosomal
      rearrangements in patients with normal phenotypes. 

PMID- 26214465
TI  - Differentiation-inducing effects of betamethasone on human glioma cell line U251.
AB  - We studied the differentiation-inducing effect of beta-methasone on human glioma
      cell line U251 cultured in vitro, and the underlying mechanism. U251 cells were
      divided into two groups: control group cells, cultured in Dulbecco's Modified
      Eagle's medium containing 10% fetal bovine serum; and medication group cells,
      treated with 15 MUM betamethasone. Morphological cell changes were observed by
      inverted microscope, cell cycle changes were ascertained by flow cytometry, and
      vimentin expression was checked by immunocytochemistry. The expression levels of
      extracellular signal-regulated protein ki-nase (ERK), phosphorylated ERK (pERK),
      and glial fibrillary acidic protein (GFAP) were assessed by western blot.
      Compared with the control group, U251 cell processes increased significantly, but
      declined 96 h after betamethasone took effect. After 48 h, the percentage of S
      phase cells decreased significantly (28.77 to 20.42%; P = 0.014); the percent-age
      of strongly positive vimentin cells decreased significantly (91 to 51%; P =
      0.0092); and the ratio of expression of GFAP protein to the internal control beta
      actin increased significantly (0.24 to 0.53; P = 0.1). The level of ERK protein
      did not change significantly 48 and 96 h after the action of betamethasone, and
      the pERK/ERK ratios were 0.37 and 0.23, respectively, which were significantly
      reduced compared with the control group (P = 0.028 and 0.006). Betamethasone has
      a significant effect on the induction and differentiation of U251 cells, and its
      mechanism may be related to the inhibition of the abnormal activation of the ERK
      signal pathway.

PMID- 26214466
TI  - Heterogeneity and diversity of ABO and Rh blood group genes in select Saudi
      Arabian populations.
AB  - In order to investigate the diversity of ABO and Rh blood group genes in the
      Saudi Arabian population, we assembled the phenotypic data of approximately
      66,000 subjects from ten representative Saudi populations: Al-Khobar, Riyadh,
      Tabuk/Madina Al-Munawaara, Jeddah, Abha, South region, Sakaka, Domah, Al-Qurayat,
      and Sweer. The frequencies of p[A], q[B], and r[O] alleles at the ABO locus were
      observed to be 0.1688, 0.1242, and 0.7070, respectively, and the frequency of the
      D allele at the Rh locus was 0.7138. The heterozygosities at the ABO and Rh loci
      were 0.4563 and 0.4086, respectively, while the combined heterozygosity was
      0.4324. Homogeneity tests revealed the population of Abha to be the most
      heterogeneous while that of Tabuk/Madina was found to be the least heterogeneous.
      Homogeneity was higher among the Northern populations while Southern populations
      demonstrated subdivisions and stratification. Gene diversity analyses yielded a
      total heterozygosity value of 0.4449. The coefficient of gene differentiation was
      0.0090. Nei's genetic distance analyses showed that there was close affinity
      between the populations of Al-Khobar and Riyadh. The largest differences were
      observed between the populations of Sakaka and Domah. Furthermore, negative
      correlations were found between p[A] and r[O] alleles, and between q[B] and r[O]
      alleles at the ABO locus. Clinal analyses revealed that the r[O] allele showed an
      increasing trend from North-East to South-West, and conversely the q[B] allele
      exhibited a decreasing trend at these coordinates. These analyses present
      interesting aspects of the blood group allele distribution across the geography
      of Saudi Arabia. 

PMID- 26214467
TI  - Manipulation of primer affinity improves high-resolution melting accuracy for
      imprinted genes.
AB  - High-resolution melting (HRM) is considered an inexpensive, rapid, and attractive
      methodology for methylation analysis. In the application of the polymerase chain
      reaction (PCR) to methylation analysis, amplification efficiencies are biased
      towards unmethylated, rather than methylated, templates: a phenomenon known as
      PCR bias. To overcome PCR bias, primers that include CpG site(s) and are fully
      complementary to the methylated sequence have been proposed. However, genes
      mapped within imprinted regions usually present higher methylation levels, and an
      unusual PCR bias towards the methylated template can therefore arise. The
      manipulation of primer affinity attempts to overcome this problem. We attempted
      to show that mismatches at the primer's methylated binding sites increase the
      area between the 50 and 100% methylation plots on the melting curves, and may
      increase HRM accuracy for samples that have high methylation levels. Sets of
      primers for imprinted genes that included CpG sites at their binding sequences
      were designed, and were complementary to methylated or unmethylated templates.
      Primers fully complementary to methylated templates produced a very small area
      between the 50 and 100% methylation plots. When using primers that were fully
      complementary to the unmethylated sequence, we were able to increase the area
      between the 50 and 100% methylation plots. Therefore, when samples are highly
      methylated, such as targets in genes mapped in imprinted regions, we propose that
      primers should favor amplification of the rarest, unmethylated sequence. Primers
      may be designed to include one CpG at its binding site and be fully complementary
      to the unmethylated template. 

PMID- 26214468
TI  - Effect of skeletal muscle fibers on porcine meat quality at different stages of
      growth.
AB  - In this study, we examined changes in meat quality and content of muscle types
      during porcine growth. The influence of the longissimus dorsi muscle fiber
      composition on meat quality and the correlation between 2 fiber-typing methods
      (histochemistry and real-time quantitative polymerase chain reaction) were
      examined. Type IIx and type IIb fibers accounted for most of the total number of
      fibers; the proportion of these fibers increased during porcine growth (75.42,
      80.09, and 79.88%, respectively, at 3 different stages of growth). There was a
      strong positive correlation between the 2 fiber-typing methods; the correlation
      coefficients of type I, IIa, and IIx+IIb fiber contents were 0.65, 0.88, and
      0.92, respectively. The a* value of meat color was significantly lower at 98 days
      and negatively correlated with white fiber content (r = -0.69, P < 0.01). Water
      holding capacity decreased during porcine growth. The drip loss parameter was
      positively correlated with type IIx+IIb fiber content (r = 0.55, P < 0.05).
      Decreased pH was strongly positively correlated with type IIx+IIb fiber content
      (r = 0.61, P < 0.01) and negatively correlated with type IIa fiber content (r = 
      0.44, P < 0.05). Therefore, we found that the composition of muscle fibers
      influenced the establishment of meat quality and its alteration during the early
      postmortem period. 

PMID- 26214469
TI  - Expression differences in TEL-AML1 fusion gene in leukemia glucocorticoid
      sensitive and -resistant cell lines.
AB  - We investigated the expression differences of the TEL-AML1 fusion gene in a
      leukemia glucocorticoid (GC)-sensitive cell line (CEM) and a GC-resistant cell
      line (Jurkat). Changes in TEL-AML1 expression before and after GC exposure were
      analyzed. Expression of GC-sensitive and GC-resistant leukemia cells following
      initial diagnosis and during treatment was simulated. Leukemia cells were divided
      into a GC-unexposed or a GC-exposed group. A methyl thiazolyl tetrazolium assay
      was used to detect cell proliferation inhibition, flow cytometry was used to
      observe cell apoptosis, reverse transcription-polymerase chain reaction was used
      to detect the mRNA expression of TEL-AML1 before and after exposure, and western
      blotting was used to analyze protein levels of TEL-AML1 before and after
      exposure. Inhibitory concentrations of 50% of cells in the Jurkat and CEM cells
      at 24 h were 382 and 9 mM, respectively, and at 48 h they were 216 and 2 mM. The
      proliferation inhibition effect of dexamethasone sodium phosphate on Jurkat cells
      was much lower than that on CEM cells. Jurkat cells showed obvious apoptosis
      after exposure to 100 mM dexamethasone sodium phosphate for 48 h. In the exposed
      group, Jurkat cells showed higher TEL-AML1 expression than did CEM cells (P <
      0.05). In the unexposed group, TEL-AML1 gene expression in Jurkat cells was not
      affected by GC exposure (P > 0.05), while the CEM cells presented significant
      differences before and after exposure (P < 0.05). Sustained high expression of
      TEL-AML1 participated in and maintained the occurrence of GC resistance.
      Inhibition of TEL-AML1 may provide a new therapeutic approach to reverse GC
      resistance. 

PMID- 26214470
TI  - Molecular variation of Sporisorium scitamineum in Mainland China revealed by
      internal transcribed spacers.
AB  - Sugarcane smut caused by the fungus Sporisorium scitamineum is a worldwide
      disease and also one of the most prevalent diseases in sugarcane production in
      mainland China. To study molecular variation in S. scitamineum, 23 S. scitamineum
      isolates from the 6 primary sugar-cane production areas in mainland, China
      (Guangxi, Yunnan, Guangdong, Hainan, Fujian, and Jiangxi Provinces), were
      assessed using internal transcribed spacer (ITS) methods. The results of ITS
      sequence analysis showed that the organisms can be defined at the genus level,
      including Ustilago and Sporisorium, and can also differentiate between closely
      related species. This method was not suitable for phylogenetic relationship
      analysis of different S. scitamineum isolates and could not provide support
      regarding their race ascription at the molecular level. The results of the
      present study will be useful for studies examining the molecular diversity of S.
      scitamineum and for establishing a genetic foundation for their pathogenicity
      differentiation and new race detection. In addition, our results can provide
      useful information for the pathogen selection principle in sugarcane smut
      resistance breeding and variety distribution.

PMID- 26214471
TI  - Rapid development of polymorphic microsatellite markers for the Amur sturgeon
      (Acipenser schrenckii) using next-generation sequencing technology.
AB  - Anthropogenic activities have seriously impacted wild resources of the Amur
      sturgeon, Acipenser schrenckii, and more information on local and regional
      population genetic structure is required to aid the conservation of this species.
      In this study, we report the development of 12 novel polymorphic microsatellite
      loci using next-generation sequencing technology, and the genotyping of 24
      individuals collected from a sturgeon farm. The results show that the mean number
      of ob-served alleles per locus is 6.6 (ranging from 2 to 17). Observed and
      expected heterozygosity values ranged from 0 to 0.958 and from 0.508 to 0.940,
      respectively. Not a single locus showed significant departure from Hardy-Weinberg
      equilibrium and no linkage disequilibrium was observed among any pairwise loci.
      These highly informative microsatellite markers will be useful for genetic
      diversity and population structure analyses of A. schrenckii and other species of
      this genus.

PMID- 26214472
TI  - Development of EST-SSR and TRAP markers from transcriptome sequencing data of the
      mango.
AB  - Mango is one of the most commercially important fruit crops in tropical and
      subtropical regions. To increase the efficiency of breeding strategies, two EST
      derived marker systems were developed in the present study using information from
      the mango fruit transcriptome. Using simple sequence repeats, 218 of 230 primer
      pairs showed stable amplification for 7 mango genotypes with amplicons ranging
      from 84 to 160 bp; 93 of the primer pairs yielded polymorphic products. The
      proportion of polymorphic bands ranged from 16.67 to 100%, with a mean of 55.64%.
      In contrast, 86 primer pairs exhibited good amplification with clear bands for
      target region amplification polymorphism analysis, and a total of 66 primer
      combinations were polymorphic. These two novel sets of EST-derived markers will
      be of use in future studies of genetic diversity, genetic map construction, and
      marker-assisted selection in mango. 

PMID- 26214473
TI  - Association between the rs3795879 G/A polymorphism of the SERPINE2 gene and
      chronic obstructive pulmonary disease: a meta-analysis.
AB  - The present study aimed to investigate the effects of the rs3795879 polymorphism
      of the SERPINE2 gene on the development of chronic obstructive pulmonary disease
      (COPD) based on a systematic meta-analysis. An extensive literature search was
      performed to retrieve previously published case-control studies on the
      polymorphisms of SERPINE2 in COPD patients. Odds ratios (ORs) with 95% confidence
      intervals (CIs) were used to assess the association between SERPINE2
      polymorphisms and risk of developing COPD. A total of 5 studies including 3034
      COPD cases and 3068 controls were incorporated in the present meta-analysis.
      Generally, no significant association was identified between the rs3795879
      polymorphism of SERPINE2 and the risk of developing COPD (G allele vs A allele:
      OR = 1.23, 95%CI = 0.97-1.32; GG vs GA: OR = 1.19, 95%CI = 0.81-1.76; GG vs AA:
      OR = 1.23, 95%CI = 0.89-1.70; dominant model: OR = 1.18, 95%CI = 0.85- 1.62;
      recessive model: OR = 1.19, 95%CI = 0.85-1.66). In addition, subgroup analyses
      according to different ethnicities and the source of controls suggest no
      statistically significant association between the rs3795879 polymorphism of
      SERPINE2 and COPD risk. The results suggest that the rs3795879 polymorphism of
      SERPINE2 is not a risk factor for COPD. 

PMID- 26214474
TI  - Pathology of the lower nasolacrimal duct mucosa at multiple time points after
      lacrimal retrograde catheterization in rabbit.
AB  - Lacrimal duct obstruction is a common eye disease, and obstruction of the
      nasolacrimal duct accounts for over 50% of these cases. Nasolacrimal duct
      obstruction is usually treated surgically. Lacrimal retrograde catheterization is
      a novel surgical approach with a high success rate and a relatively high
      recurrence rate. In this study, we examined the postoperative pathological
      changes in the lower nasolacrimal duct mucosa at multiple time points (2, 4, 6,
      8, 10, 12, and 14 weeks) after retrograde lacrimal dilated drainage tube
      implantation in rabbits. One side of the nasolacrimal duct was obstructed in 14
      rabbits. Compared to the control side, the 2-, 4-, 6-, and 8-week groups
      presented no obvious changes in hematoxylin and eosin (H&E)-stained tissue. The
      10-week group presented isolated granulomas. The 12- and 14-week groups presented
      scattered granulomas. The granulomas were smaller and the density of fibroblasts
      was lower in the 12-week group compared with the 14-week group. Transforming
      growth factor-beta1 immunohistochemistry resulted in strong immunoreactivity in
      the 14-week group and weak immunoreactivity in the 12-week group, and the
      difference was statistically significant (P < 0.05). Fibroblast apoptosis was
      observed in the 4- and 6-week groups, and disorganized fibers were observed in
      the 10-week group. Most fibroblasts in the 12- and 14-week groups were the active
      type with mechanocytes. Granulomas were induced after a long time by the
      implantation of silicone tubes in rabbits. Thus, recurrent obstructions of the
      nasolacrimal duct may be caused by granulomas, progressive fibrosis, and/or
      adhesion of the surrounding tissues. 

PMID- 26214475
TI  - Transferability of microsatellite markers of Capsicum annuum L. to C. frutescens
      L. and C. chinense Jacq.
AB  - In order to support further genetic, diversity, and phylogeny studies of Capsicum
      species, the transferability of a Capsicum annuum L. simple sequence repeat (SSR)
      microsatellite set was analyzed for C. frutescens L. ("malagueta" and "tabasco"
      peppers) and C. chinense Jacq. (smell peppers, among other types). A total of 185
      SSR primers were evaluated in 12 accessions from 115 C. frutescens L. and 480 C.
      chinense Jacq, representing different types within each species. Transferability
      to C. frutescens L. and C. chinense Jacq. occurred for 116 primers (62.7%).
      Nineteen (16.37%) were polymorphic in C. frutescens L. and 36 (31.03%) in C.
      chinense Jacq., 17 of which were coincident and could be used to analyze samples
      obtained for the 2 species. Among these primers, CA49 showed a different
      amplitude range of alleles between the 2 species (130-132 base pairs for C.
      frutescens L. and 120-128 base pairs for C. chinense Jacq.), and could
      differentiate the species. A total of 55 alleles were identified among the 19
      polymorphic SSR loci among accessions of C. frutescens L., with the number of
      alleles per locus ranging from 2 to 5, a mean of 2.89, and the polymorphic
      information content ranging from 0.30 to 0.65. The number of alleles identified
      in C. chinense Jacq. was 119, ranging from 2 to 5 alleles per locus, an average
      of 3.30, and polymorphic information content from 0.19 to 0.68. The C. annuum L.
      SSR primers were most often transfer-able and polymorphic for C. frutescens L.
      and C. chinense Jacq., and we present a set of SSR for each species.

PMID- 26214476
TI  - In silico analysis of gene content in tomato genomic regions mapped to the Ty-2
      resistance gene.
AB  - Tomato yellow leaf curl virus is one of the main diseases affecting tomato
      production worldwide. Previous studies have shown that Ty-2 is an important
      resistance gene located between molecular markers C2_At2g28250 (82.3 cM) and
      T0302 (89.0 cM), and exhibits strong resistance to tomato yellow leaf curl virus
      in Asia. In this study, Ty-2 candidate genes were subjected to bioinformatic
      analysis for the sequenced tomato genome. We identified 69 genes between
      molecular markers C2_At2g28250 and T0302, 22 of which were disease-related
      resistant genes, including nucleotide binding site-leucine-rich repeat disease
      resistance genes, protease genes (protein kinase, kinase receptor, and protein
      isomerase), cytochromes, and transcription factors. Expressed sequence tag
      analysis revealed that 77.3% (17/22) of candidate disease-resistance genes were
      expressed, involving 143 expressed sequence tags. Based on full-length cDNA
      sequence analysis, 7 candidate genes were found, 4 of which were involved in
      tomato responses to pathogens. Microarray expression analysis also showed that
      most candidate genes were involved in the tomato responses to multiple pathogens,
      including fungi, viruses, and bacteria. RNA-seq expression analysis revealed that
      all candidate genes participated in tomato growth and development.

PMID- 26214477
TI  - Reduced cortisol in the absence of bacterial infection in patients with hepatitis
      B virus cirrhosis.
AB  - In liver cirrhosis with bacterial infection, hepatoadrenal syndrome has been
      described recently as a progressive impairment in the adrenocortical reserve,
      with deficient production or action of glucocorticoids resulting in adrenal
      insufficiency. The aim of this study was to explore the characteristics of
      cortisol in hepatitis B virus (HBV) cirrhosis patients in the absence of
      bacterial infection. Fasting peripheral venous blood samples were collected from
      107 patients with HBV cirrhosis in the absence of bacterial infection and 18
      patients with chronic hepatitis B (CHB) infection at 7 a.m. in the morning. The
      carbohydrate, cortisol-binding globulin, routine chemistry, liver function, and
      hepatitis B indicators were tested, and free cortisol was calculated. Cortisol
      (COR) levels were 18.72 +/- 6.60 MUg/dL in the CHB group and 14.20 +/- 7.55
      MUg/dL in the HBV cirrhosis group (P = 0.002). COR levels were 15.11 +/- 5.56,
      14.88 +/- 6.96, and 12.68 +/- 8.36 MUg/dL in Child-Pugh class A, B, and C
      cirrhotic patients, respectively (P = 0.006). Adrenocorticotropic hormone levels
      were 35.42 +/- 24.49, 26.57 +/- 15.72, and 19.65 +/- 10.72 pg/mL in Child-Pugh
      class A, B, and C cirrhotic patients, respectively (P = 0.000). Patients with HBV
      cirrhosis had significantly lower serum COR levels compared with those of CHB
      patients, even if they are in the absence of bacterial infection. COR levels
      negatively correlated with Child-Pugh scores. The hypothalamic-pituitary-adrenal
      axis might be damaged in patients with HBV cirrhosis. 

PMID- 26214478
TI  - Characterization of a TIR-NBS-LRR gene associated with downy mildew resistance in
      grape.
AB  - Grapevine downy mildew, caused by Plasmopara viticola, is a devastating disease
      that results in considerable economic losses as well as environmental damage
      through the repeated application of fungicides. The nucleotide-binding site
      leucine-rich repeat gene family functions in plant immunoactivity against various
      pathogens and pests. In this study, the 5' and 3' ends of the resistance gene
      homology fragment RGA5 were obtained by rapid amplification of cDNA ends. The
      4282-base pair full-length cDNA was obtained using gene-specific primers, and the
      corresponding 1335-amino acid protein sequence contained characteristic
      nucleotide-binding site leucine-rich repeat domains of plant resistance proteins,
      including the toll-interleukin receptor type region. Expression of RGA5 during P.
      viticola infection and abiotic stress was investigated using quantitative real
      time polymerase chain reaction. The results showed that treatment with P.
      viticola and 4 abiotic stimuli (salicyclic acid, methyl-jasmonate, abscisic acid,
      H2O2) significantly induced RGA5 within 12 days of inoculation. Therefore, RGA5
      may play a critical role in protecting grapevines against P. viticola via
      signaling pathways involving these molecules. 

PMID- 26214479
TI  - Relationship between UV-irradiated HaCaT cell cytokines and Th1/Th2 imbalance.
AB  - We have previously found that an imbalance of Tc1/Tc2 T cell subtypes in vivo
      impacts the development of photodermatitis. The aim of this study was to
      investigate the relationship between cytokines derived from keratinocytes
      exposure to UV and the imbalance of Th subgroups. We used different doses of UVA
      and UVB to irradiate HaCaT cells. Twelve hours after irradiation, the expression
      of IL-10R, IL-4R, IL-12R, and IFN-gammaR proteins was observed using the S-P
      method, and the percentage of positive cells calculated. Protein levels of the
      respective ligands in the supernatant was measured by ELISA. Our results showed
      low levels of expression of the interrogated proteins in unirradiated HaCaT
      cells, and little or no expression could be detected in the supernatant. Little
      or no expression was also observed for IL-12R and IFN-gammaR 12 h after UVA or
      UVB irradiation. However, the expression of IL-10R and IL-10 was upregulated 12 h
      following UVB irradiation, as well as following lower dose UVA irradiation. In
      contrast, higher dose UVA decreased the expression of IL-10R and IL-10. The
      expression of IL-4R was increased following high doses of UVA and UVB
      irradiation, whereas no expression was observed after lower dose UV exposure.
      There was no change in IL-4 secretion into the supernatant. Our results
      demonstrate that the effects of UV exposure on keratinocyte-derived cytokines are
      different according to the doses of irradiation and the types of cytokines, and
      suggest that keratinocyte-derived cytokines after UV exposure might cause an
      imbalance of Th1/Th2. 

PMID- 26214480
TI  - Characterization of microsatellite markers for the Restinga Antwren, Formicivora
      littoralis (Thamnophilidae), an endangered bird endemic to Brazil.
AB  - Molecular markers are important tools in determining parentage, gene flow, and
      the genetic structure of species. In the case of rare, endemic, and/or threatened
      species, these markers can be used to understand key ecological questions and
      support conservation actions. We developed seven microsatellite markers for the
      only bird endemic to the Restinga ecosystem. Microsatellite loci were isolated
      from a library that was based on 10 individuals (six males and four females).
      Primers were tested in 107 individuals of the same population. The number of
      alleles per locus ranged from 4 to 19, and the observed and expected
      heterozygosity varied from 0.15 to 0.84 and from 0.60 to 0.89, respectively. We
      expect that the polymorphic microsatellite loci we describe will be useful for
      other studies, particularly in the Tropics. 

PMID- 26214481
TI  - Characterization of FeDREB1 promoter involved in cold- and drought-inducible
      expression from common buckwheat (Fagopyrum esculentum).
AB  - C-repeat-binding factor (CBF)/dehydration-responsive element (DREB) transcription
      factors play key roles in plant stress responses. However, little information is
      available on the regulation of CBF/DREB expression. In this study, we isolated
      and characterized the FeDREB1 promoter sequence from the common buckwheat
      accession Xinong 9976. To identify the upstream region of the FeDREB1 gene
      required for promoter activity, we constructed a series of FeDREB1 promoter
      deletion derivatives. Each deletion construct was analyzed through Agrobacterium
      mediated transient transformation in tobacco leaves treated with 4 degrees C cold
      or drought stress. Promoter-beta-glucuronidase fusion assays revealed that the
      pCD1 (-270 bp) deletion in the upstream region of FeDREB1 could activate
      expression of the GUS gene at 4 degrees C. The pCD1 (-270 bp), pCD2 (-530 bp),
      and pCD3 (-904 bp) deletion induced low-level GUS expression under drought
      stress. However, the pCD4 (-1278 bp) deletion clearly activated GUS gene
      expression. Our results suggest that sections pCD1 (-270 bp) and pCD4 (-1278 bp)
      in the FeDREB1 gene promoter are new sources of induced promoters for adversity
      resistance breeding in plant genetic engineering. 

PMID- 26214482
TI  - A simple, fast, and inexpensive CTAB-PVP-silica based method for genomic DNA
      isolation from single, small insect larvae and pupae.
AB  - In this study, we report a modified CTAB-PVP method combined with silicon dioxide
      (silica) treatment for the extraction of high quality genomic DNA from a single
      larva or pupa. This method efficiently obtains DNA from small specimens, which is
      difficult and challenging because of the small amount of starting tissue.
      Maceration with liquid nitrogen, phenol treatment, and the ethanol precipitation
      step are eliminated using this methodology. The A260/A280 absorbance ratios of
      the isolated DNA were approximately 1.8, suggesting that the DNA is pure and can
      be used for further molecular analysis. The quality of the isolated DNA permits
      molecular applications and represents a fast, cheap, and effective alternative
      method for laboratories with low budgets. 

PMID- 26214483
TI  - Molecular cloning, characterization, and expression of vacuolar-type-H+-ATPase B1
      (VHAB1) gene in the gill of Anguilla marmorata.
AB  - We explored the molecular mechanism of the regulation of vacuolar-type-H+-ATPase
      B1 (VHAB1) in elvers in the response to salinity. The full-length cDNA of VHAB1
      in Anguilla marmorata (designated as AmVHAB1), which was 1741 base pairs (bp) in
      length, was found to encompass a 1512-bp open reading frame encoding a
      polypeptide with 503 amino acids (55.9 kDa), an 83-bp 5'-untranslated region, and
      a 146-bp 3'-untranslated region. The mRNA and protein expression levels of
      AmVHAB1 in the gill were evaluated at different time points (0, 1, 3, 6, 12, 24,
      48, 72, and 96 h, and 15 days) during the exposure to various salinity levels (0,
      10, and 250/00). The results indicated that the expression levels of AmVHAB1 mRNA
      in the gill significantly increased and reached the highest level at 1 h exposure
      in the brackish water (BW, 100/00) group and at 6 h exposure in the seawater (SW,
      250/00) group. The salinity level affected the relative expression level of
      AmVHAB1 mRNA in the gill, which was increased by approximately 44-fold in the SW
      group when compared with that in fresh water. Immunoblotting analysis showed that
      VHA expression was significantly higher in the BW and SW groups, with the highest
      expression level was detected at 96 h exposure. We found that the AmVHAB1 gene in
      elvers from A. marmorata plays an important role in the adaptation to seawater.

PMID- 26214484
TI  - Correlation between MTHFR gene methylation and pre-eclampsia, and its clinical
      significance.
AB  - We investigated the correlation between 5,10-methylenetetrahydrofolate reductase
      (MTHFR) gene methylation and pre-eclampsia, and its clinical significance, by
      comparing methylation in the MTHFR gene promoter of the placenta and peripheral
      venous blood in pre-eclampsia and normal gravidas. We enrolled 259 gravidas from
      the People's Liberation Army 202nd Hospital, China, between January 2011 and
      September 2011, including 127 pre-eclampsia and 132 nor-mal gravidas. Methylation
      levels of the MTHFR gene in placentas in two sets of gravidas were detected by
      methylation-specific polymerase chain reaction, plasma homocysteine levels were
      detected by enzyme-linked immunosorbent assay, and folic acid and vitamin B12
      levels were detected by electrochemiluminescence. The chi-square test results
      were analyzed using the SPSS19.0 statistical software. In placentas, the
      methylation indices were 26.8% (34/127) and 15.2% (20/132) in the pre-eclampsia
      and normal groups, respectively (chi(2) = 5.30, P < 0.05, odds ratio (OR) = 2.04,
      95% confidence interval (95%CI) = 1.10-3.73). In peripheral venous blood, the
      methylation indices were 22.8% (29/127) and 12.1% (16/132) in pre-eclampsia and
      normal groups, respectively (chi(2) = 5.17, P < 0.05, OR = 2.15, 95%CI = 1.11
      4.15). The plasma methylation level of the pre-eclampsia group was consistent
      with the normal group. The plasma homocysteine level in the pre-eclampsia group
      was higher than in the normal group (P < 0.05). Levels of folic acid and vitamin
      B12 in the pre-eclampsia and normal groups were not statistically significant (P
      > 0.05). Patients with pre-eclampsia have hypermethylation in the MTHFR gene
      promoter, which may be one of its causes.

PMID- 26214485
TI  - Protective effect and mechanism of probucol in the treatment of spinal cord
      injury.
AB  - To investigate the effects of probucol on the treatment of spinal cord injury in
      rat, 80 rats were randomly divided into two groups of 40: a group treated with
      probucol and a control group. Allen's method was used to establish a rat model of
      spinal cord injury. After establishment, probucol (500 mg.kg(-1).day(-1)) was
      intraperitoneally injected into the treatment group rats for 1 week, while the
      same amount of saline was used to treat the control group. On days 1, 7, 14, 21,
      and 28 after treatment, the function of rats' spinal cord was evaluated according
      to the Bresnahan locomotor rating scale. Serum protein and mRNA levels of the
      cytokines [interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and
      interleukin (IL)-17] were measured using enzyme-linked immunosorbent assay and
      quantitative polymerase chain reaction, respectively. Protein levels of IFN
      gamma, TNF-alpha, IL-17, and the downstream markers signal transducer and
      activator of transcription (STAT)-1 and STAT-3 were measured using western blot.
      In addition, the oxidative stress-related parameters, superoxide dismutase (SOD)
      and malondialdehyde (MDA), were also measured. It was found that compared to
      control group, rats from the treatment group had significantly lower levels of
      IFN-gamma, TNF-alpha, and IL-17 (P < 0.05) on days 1 and 7, as well as lower MDA
      levels and higher SOD activity on days 7, 21, and 28 (P < 0.05). In summary,
      probucol improved the recovery of locomotion function after spinal cord injury in
      rats through downregulation of inflammation and upregulation of anti-oxidative
      activity. 

PMID- 26214486
TI  - Screening of differentially-expressed genes in the muscles of rabbit breeds with
      expression profile chip.
AB  - The molecular mechanism underlying muscle development in rabbits is not well
      understood. In the current study, differentially-expressed genes were scanned
      using an expression profile chip in New Zealand white rabbits (introduced breed)
      and Fujian yellow rabbits (local breed), and some of the genes were tested using
      reverse transcription-polymerase chain reaction. The amplification results were
      consistent with the microarray data. Fourteen and 13 genes involved in muscle
      development were identified in the dorsal longissimus and leg muscles,
      respectively. Myh6, Myh7, Myh7b, Myo5b, Tnnc1, Tpm3, and Acta2 were scanned in
      the longissimus and leg muscles. Thus, these genes may be involved in muscle
      fiber formation and muscle development in rabbits. This study provides a
      theoretical basis for improving meat quality, as well as for the future
      development and utilization of local meat rabbit breeds. 

PMID- 26214487
TI  - Estimation of genetic structure of a Mycosphaerella musicola population using
      inter-simple sequence repeat markers.
AB  - Among the diseases affecting banana (Musa sp), yellow Sigatoka, caused by the
      fungal pathogen Mycosphaerella musicola Leach, is considered one of the most
      important in Brazil, causing losses throughout the year. Understanding the
      genetic structure of pathogen populations will provide insight into the life
      history of pathogens, including the evolutionary processes occurring in
      agrosystems. Tools for estimating the possible emergence of pathogen variants
      with altered pathogenicity, virulence, or aggressiveness, as well as resistance
      to systemic fungicides, can also be developed from such data. The objective of
      this study was to analyze the genetic diversity and population genetics of M.
      musicola in the main banana-producing regions in Brazil. A total of 83 isolates
      collected from different banana cultivars in the Brazilian states of Bahia, Rio
      Grande do Norte, and Minas Gerais were evaluated using inter-simple sequence
      repeat markers. High variability was detected between the isolates, and 85.5% of
      the haplotypes were singletons in the populations. The highest source of genetic
      diversity (97.22%) was attributed to variations within populations. Bayesian
      cluster analysis revealed the presence of 2 probable ancestral groups, however,
      showed no relationship to population structure in terms of collection site, state
      of origin, or cultivar. Similarly, we detected noevidence of genetic
      recombination between individuals within different states, indicating that
      asexual cycles play a major role in M. musicola reproduction and that long
      distance dispersal of the pathogen is the main factor contributing to the lack of
      population structure in the fungus. 

PMID- 26214488
TI  - Genetic structure and genetic diversity of single-variety Lonicera macranthoides
      populations in China, as indicated by SCoT markers.
AB  - Lonicera macranthoides is an important traditional Chinese herb. The lack of
      information regarding the genetic structure and genetic relationships among its
      cultivars has hindered the conservation and utilization of this resource. This
      study used start codon targeted markers to assess the genetic diversity and other
      genetic characteristics of five single-variety L. macranthoides populations in
      China. Using 22 primers produced a total of 266 bands, of which 227 were
      polymorphic, indicating a high level of polymorphism. At the species level,
      genetic diversity was high: percentage of polymorphic loci (PPB) = 85.34%,
      effective number of alleles (NE) = 1.3479, Nei's gene diversity (H) = 0.2075, and
      Shannon's information index (Hsp, species level) = 0.3198. However, at the
      varietal population level, genetic diversity was lower, with averages of: PPB =
      19.74%, NE = 1.0946, H = 0.0561, Hpop = 0.0850 (population level). Nei's genetic
      differentiation coefficient was 0.7319, which is consistent with Shannon's
      population genetic differentiation coefficient (0.7324). This indicates that most
      of the genetic variation in this species exists among the varietal populations.
      The differentiation among varieties may have been caused by artificial selection,
      mode of reproduction, and barriers to gene flow (0.1831). The genetic similarity
      coefficient ranged from 0.7222 to 0.9419. Phylogenetic analysis showed the five
      varieties to form two major clades. Results suggest that cultivar breeders should
      strengthen the exchange of germplasm and increase the mutual penetration of
      useful genes, which would broaden the hereditary basis of L. macranthoides. 

PMID- 26214489
TI  - Meta-analysis of angiotensin-converting enzyme insertion/deletion polymorphism
      and myocardial infarction in Han Chinese.
AB  - It has been suggested that the angiotensin-converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphism is linked to susceptibility to myocardial
      infarction (MI). In this study, we performed a meta-analysis to assess the
      relationship between ACE I/D polymorphism and MI in the Chinese Han population.
      Eight studies including a total of 1609 subjects were selected for inclusion in
      the analysis. The references were retrieved using the PubMed and China National
      Knowledge Infrastructure databases. The analyses were performed using the STATA
      12.0 software. ORs and 95%CI were assessed after the collected data were pooled
      for analysis. There was a significant association between ACE I/D polymorphism
      and MI in the Chinese Han population (II vs DD: OR = 0.40, 95%CI = 0.31-0.53; II
      vs DI: OR = 0.72, 95%CI = 0.57-0.91; the dominant model: OR = 1.74, 95%CI = 1.41
      2.16; the recessive model: OR = 0.47, 95%CI = 0.38-0.60). The sensitivity
      analysis further confirmed the result. Publication bias was not observed in this
      meta-analysis. The ACE I/D polymorphism may be a risk factor for MI in the
      Chinese Han population. However, larger studies with a stratified case-control
      population and biological characterization are needed to validate this finding.

PMID- 26214490
TI  - Stripe rust resistance and dough quality of new wheat - Dasypyrum villosum
      translocation lines T1DL*1V#3S and T1DS*1V#3L and the location of HMW-GS genes.
AB  - The transfer of agronomically useful genes from wild wheat species into
      cultivated wheat is one of the most effective approaches to improvement of wheat
      varieties. To evaluate the transfer of genes from Dasypyrum villosum into
      Triticum aestivum, wheat quality and disease resistance was evaluated in two new
      translocation lines, T1DL*1V#3S and T1DS*1V#3L. We examined the levels of stripe
      rust resistance and dough quality in the two lines, and identified and located
      the stripe rust resistant genes and high molecular weight glutenin subunit (HMW
      GS) genes Glu-V1 of D. villosum. Compared to the Chinese Spring (CS) variety,
      T1DL*1V#3S plants showed moderate resistance to moderate susceptibility to the
      stripe rust races CYR33 and Su11-4. However, T1DS*1V#3L plants showed high
      resistance or immunity to these stripe rusts. The genes for resistance to stripe
      rust were located on 1VL of D. villosum. In comparison to CS, the dough from
      T1DS*1V#3L had a significantly shorter developing time (1.45 min) and stable time
      (1.0 min), a higher weakness in gluten strength (208.5 FU), and a lower
      farinograph quality index (18). T1DL*1V#3S had a significantly longer developing
      time (4.2 min) and stable time (5.25 min), a lower weakness in gluten strength
      (53 FU) and a higher farinograph quality index (78.5). We also found that
      T1DS*1V#3L had reduced gluten strength and dough quality compared to CS, but
      T1DL*1V#3S had increased gluten strength and dough quality. The results of SDS
      PAGE analysis indicated that Glu-V1 of D. villosum was located on short arm 1VS
      and long arm 1VL. These results prove that the new translocation lines,
      T1DS*1V#3L and T1DS*1V#3L, have valuable stripe rust resistance and dough quality
      traits that will be important for improving wheat quality and resistance in
      future wheat breeding programs.

PMID- 26214491
TI  - Lentinan depresses 3T3-L1 fat cell formation by inhibiting PPARgamma/AKT
      signaling pathway.
AB  - We investigated the mechanism of the effect of lentinan on 3T3-L1 fat cell
      formation by inhibiting the peroxisome proliferator-activated receptor gamma
      (PPARgamma)/protein kinase B (AKT) signaling pathway. 3T3-L1 fat cells were
      treated with 80 mM lentinan with or without the PPARgamma activator, 100 mM
      rosiglitazone for 24 h. Reverse transcription-polymerase chain reaction was
      applied to detect PPARgamma and AKT mRNA expression levels. Western blotting was
      used to detect AKT protein expression level. Compared with the control group, 80
      mM lentinan increased PPARgamma mRNA expression and downregulated AKT mRNA
      expression. After treatment with rosiglitazone, PPARgamma mRNA expression
      increased by 78% (P < 0.05), while AKT mRNA expression decreased by 71% (P <
      0.05). Lentinan treatment decreased AKT protein expression by 33%, and AKT
      protein expression in the lentinan and rosiglitazone co-treatment group was
      reduced by 28% compared with the lentinan treatment group. We found that 80 mM
      lentinan increased PPARgamma mRNA expression and reduced AKT mRNA. Combination
      treatment with rosiglitazone increased this effect. This suggests that lentinan
      can depress 3T3-L1 fat cell formation by inhibiting the PPARgamma/AKT signaling
      pathway.

PMID- 26214492
TI  - Correlation of plasma soluble cluster of differentiation 40 ligand, alpha
      fetoprotein A, and pregnancy-associated plasma protein A with carotid plaque in
      patients with ischemic stroke.
AB  - This study investigated the correlation of plama levels of inflammatory
      biomarkers [soluble cluster of differentiation 40 ligand (sCD40L), alpha
      fetoprotein A (fetuin-A), and pregnancy-associated protein A (PAPP-A)] with
      carotid plaque in patients with acute ischemic stroke. After undergoing color
      Doppler ultrasonography of the bilateral carotid arteries, 200 patients with
      acute ischemic stroke were grouped into plaque and non-plaque groups. The plaque
      group was further divided into stable and unstable plaque sub-groups by carotid
      plaque stability. Inter-group and -subgroup comparisons included demographic
      characteristics, current condition and medical history, and clinical laboratory
      and plama inflammatory biomarker data, and logistic regression explored the
      correlations between plama inflammatory biomarker levels and carotid plaques.
      Significantly higher sCD40L and fetuin-A levels were found in the plaque group
      than in the non-plaque group (all P < 0.05), with odds ratios (plaque vs non
      plaque) of 6.372 and 4.101, respectively. Increased plama inflammatory biomarker
      levels were accompanied by a high risk of carotid plaque formation. Similarly,
      significantly higher plama sCD40L and PAPP-A levels were found in the unstable
      plaque subgroup than in the stable plaque subgroup (all P < 0.05), and the odds
      ratios (unstable vs stable) were 5.290 and 4.125, respectively. Increased plama
      inflammatory biomarker levels were accompanied by a high risk of carotid plaque
      instability. The study findings showed that plasma sCD40L, fetuin-A, and PAPP-A
      levels are associated with carotid plaque formation and instability. Fetuin-A and
      sCD40L might be predictors of carotid plaque formation, while PAPP-A and sCD40L
      might be predictors of carotid plaque instability. 

PMID- 26214493
TI  - Selection and molecular identification of fungal isolates that produce
      xylanolytic enzymes.
AB  - Xylan is a heteropolysaccharide and its complete hydrolysis involves a complex
      set of xylanolytic enzymes. Fungal xylanases have been widely used in the
      holocellulose industry to obtain by-products or for its elimination. The aim of
      this study was to select and identify filamentous fungi from different ecosystems
      that produce extracellular xylanases showing biotechnological potential. One
      hundred three fungal isolates were obtained from orchard, horticultural, and
      forest ecosystems. The ability of fungi to degrade xylan was measured by
      quantifying their xylanolytic indices after growth on solid culture media and
      their extracellular xylanolytic and cellulolytic activities after submerged
      fermentation. All fungal isolates grew on solid medium supplemented with xylan as
      the sole carbon source, but only 44% of isolates showed xylanolytic indices
      greater than 1.0. In submerged fermentation, 39% of the fungi tested showed no
      cellulolytic activity. Filamentous fungi were chosen from correspondence analysis
      and were identified by molecular tools using internal transcribed spacers. One of
      the 9 isolates selected belonged to the Phoma genus and the remaining were from
      the Fusarium genus. Fusarium solani (isolate 59) showed the highest xylanolytic
      index (0.964 +/- 0.042), rapid growth on solid medium (1.233 +/- 0.050 cm/day),
      significant xylanolytic activity (3.823 +/- 0.210 U/mg), and a total deficiency
      of cellulolytic activity compared to other fungal isolates. In the zymogram, a
      clear zone was observed, indicating that F. solani possesses at least 1 xylanase.
      Fusarium solani was selected for its ability to produce extracellular xylanases
      with biotechnological potential. 

PMID- 26214494
TI  - Propofol suppresses proliferation and invasion of gastric cancer cells via
      downregulation of microRNA-221 expression.
AB  - Propofol is one of the extensively and commonly used intravenous anesthetic
      agents. The current study aimed to evaluate the effects of propofol on the
      behavior of human gastric cancer cells and the molecular mechanisms of this
      activity. The effects of propofol on SGC7901 and AGS cell proliferation,
      apoptosis, and invasion were detected by MTT assay, flow cytometric analysis, and
      matrigel invasion assay. Real-time polymerase chain reaction (PCR) was used to
      assess microRNA (miR)-221 expression. miR-221 mimics were transfected into
      SGC7901 and AGS cells to assess the role of miR- 221 in propofol-induced anti
      tumor activity. Propofol significantly inhibited cell proliferation and invasion
      and promoted apoptosis of SGC7901 and AGS cells. Propofol also efficiently
      reduced miR-221 expression. Moreover, transfection of miR-221 mimics reversed the
      effects of propofol on the biological behavior of gastric cancer cells. Propofol
      can effectively inhibit proliferation and invasion and induce apoptosis of
      gastric cancer cells through, at least partly, downregulation of miR-221
      expression. 

PMID- 26214495
TI  - Urinary L-FABP as a mortality predictor in <5-year-old children with sepsis in
      Bangladesh.
AB  - BACKGROUND: Although sepsis is often associated with high mortality in severely
      malnourished children, data are very limited on appropriate diagnostic tools to
      predict mortality. We examined the role of urinary liver-type fatty acid-binding
      protein (L-FABP) in children <5 years old with sepsis who died. METHODS: This
      prospective observational study was conducted at the Dhaka Hospital of the
      International Centre for Diarrhoeal Disease Research, Bangladesh. Children aged 6
      59 months admitted with sepsis from April 2010 to December 2011 were enrolled.
      Comparison of clinical and laboratory characteristics was made between children
      who survived (n = 83) and those who did not survive (n = 22). RESULTS: On
      multiple Poisson regression analysis, after adjusting for potential confounders
      such as mid-upper arm circumference < 115 mm, plasma albumin < 2.5 g/dL,
      potassium > 5.0 mmol/L, and blood urea nitrogen > 20 mg/dL on admission, first
      urine L-FABP >= 370 ng/mL (relative risk [RR], 2.76; 95%CI: 1.22-6.25), weight
      for-length/height z score < -3 (RR, 2.54; 95%CI: 1.26-5.09), capillary refilling
      time > 2.0 s (RR, 5.16; 95%CI: 1.46-18.3), and sodium > 160 mmol/L (RR, 2.72;
      95%CI: 1.07-6.90) were identified as significant risk factors of mortality in
      children with sepsis. Diagnostic performance of first urine L-FABP was analyzed
      using receiver operating characteristic curve, and the area under the curve was
      0.647 (95%CI: 0.500-0.795). CONCLUSION: Urinary L-FABP may be a useful predictor
      of mortality in septic children. Urinary examination is non-invasive and easy to
      apply at the bedside.

PMID- 26214496
TI  - High diversity of non-sporulating moulds in respiratory specimens of
      immunocompromised patients: should all the species be reported when diagnosing
      invasive aspergillosis?
AB  - Non-sporulating moulds (NSMs) isolated from respiratory specimens are usually
      discarded without further testing although they may have pathogenic effects in
      immunocompromised patients. The objective of this study was to determine the
      identity and frequency of NSMs in patients with haematological malignancies. We
      analysed the mycological results of 251 consecutive respiratory samples from 104
      haematology patients. Yeast and sporulating moulds were identified at the
      genus/species level according to their phenotypic features. NSMs were identified
      by internal transcribed spacer (ITS) sequencing. We detected 179 positive
      samples, of which 10.1% (18/179) were mixtures of moulds and 26.3% (47/179) were
      mixtures of moulds and yeast. We identified 142 moulds belonging to 11 different
      genera/species or groups, with Aspergillus fumigatus (n = 50), Penicillium spp.
      (n = 31) and NSM (n = 24) being the most frequently isolated species. Twenty-two
      NSMs were successfully sequenced: 18 were basidiomycetes and six were
      ascomycetes, corresponding to 16 different genera/species. NSMs were isolated
      with A. fumigatus in the same sample or in a subsequent sample in five patients
      with probable invasive aspergillosis. The conclusion is that the respiratory
      specimens of immunocompromised patients frequently contain very diverse mould
      species that may increase the virulence of pathogenic species. Reporting all
      mould species isolated when diagnosing invasive fungal infection could test this
      hypothesis.

PMID- 26214497
TI  - There's more than one way to conduct a replication study: Beyond statistical
      significance.
AB  - As the field of psychology struggles to trust published findings, replication
      research has begun to become more of a priority to both scientists and journals.
      With this increasing emphasis placed on reproducibility, it is essential that
      replication studies be capable of advancing the field. However, we argue that
      many researchers have been only narrowly interpreting the meaning of replication,
      with studies being designed with a simple statistically significant or
      nonsignificant results framework in mind. Although this interpretation may be
      desirable in some cases, we develop a variety of additional "replication goals"
      that researchers could consider when planning studies. Even if researchers are
      aware of these goals, we show that they are rarely used in practice-as results
      are typically analyzed in a manner only appropriate to a simple significance
      test. We discuss each goal conceptually, explain appropriate analysis procedures,
      and provide 1 or more examples to illustrate these analyses in practice. We hope
      that these various goals will allow researchers to develop a more nuanced
      understanding of replication that can be flexible enough to answer the various
      questions that researchers might seek to understand.

PMID- 26214498
TI  - Nonequivalence of measurement in latent variable modeling of multigroup data: A
      sensitivity analysis.
AB  - In studies of multiple groups of respondents, such as cross-national surveys and
      cross-cultural assessments in psychological or educational testing, an important
      methodological consideration is the comparability or "equivalence" of measurement
      across the groups. Ideally full equivalence would hold, but very often it does
      not. If nonequivalence of measurement is ignored when it is present,
      substantively interesting comparisons between the groups may become distorted. We
      consider this question in multigroup latent variable modeling of multiple-item
      scales, specifically latent trait models for categorical items. We use numerical
      sensitivity analyses to examine the nature and magnitude of the distortions in
      different circumstances, and the factors that affect them. The results suggest
      that estimates of multigroup latent variable models can be sensitive to
      assumptions about measurement, in that nonequivalence of measurement does not
      need to be extreme before ignoring it may substantially affect cross-group
      comparisons. We also discuss the implications of such findings on the analysis of
      large comparative studies.

PMID- 26214499
TI  - A fluorescent G-quadruplex probe for the assay of base excision repair enzyme
      activity.
AB  - A sensitive and selective assay of uracil DNA glycosylase (UDG) activity is
      developed by utilizing a G-quadruplex probe incorporating 2-aminopurine (2-AP),
      based on a novel design that excision reaction promoted by UDG triggers the
      formation of G-quadruplex structure with significant fluorescence enhancement of
      2-AP within the probe. 

PMID- 26214500
TI  - False pop out.
AB  - A single, unique target often pops out quickly and efficiently from a field of
      homogenous distractors in visual search. Pop out has helped shape theories of
      visual attention and feature integration as well as to identify basic features in
      human vision. Here we report a new phenomenon, false pop out, wherein one of the
      homogenous distractors competes with the singleton target to pop out, perhaps by
      breaking an overall grouping or pattern emerging from the display. We show the
      effect occurs with more than 1 type of stimulus, and we discuss the implications
      of such a counterintuitive finding for theories of visual search.

PMID- 26214501
TI  - Endogenous strategy in exploration.
AB  - We examined the characteristics of endogenous exploratory behaviors in a
      generalized search task in which guidance signals (e.g., landmarks, semantics,
      visual saliency, layout) were limited or precluded. Individuals looked for the
      highest valued cell in an array and were scored on the quality of the best value
      they could find. Exploration was guided only by the cells that had been
      previously examined, and the value of this guidance was manipulated by adjusting
      spatial autocorrelation to produce relatively smooth and rough landscapes-that
      is, arrays in which nearby cells had unrelated values (low correlation = rough)
      or similar values (high correlation = smooth). For search in increasingly rough
      as compared with smooth arrays, we found reduced performance despite increased
      sampling and increased time spent searching after revelation of a searcher's best
      cell. Spatially, sampling strategies tended toward more excursive, branching, and
      space-filling patterns as correlation decreased. Using a novel generalized
      recurrence analysis, we report that these patterns reflect an increase in
      systematic search paths, characterized by regularized sweeps with localized
      infilling. These tendencies were likewise enhanced for high-performance as
      compared with low-performance participants. The results suggest a trade-off
      between guidance (in smooth arrays) and systematicity (in rough arrays), and they
      provide insight into the particular strategic approaches adopted by searchers
      when exogenous guiding information is minimized.

PMID- 26214502
TI  - Flexible human collective wisdom.
AB  - Group decisions typically outperform individual decisions. But how do groups
      combine their individual decisions to reach their collective decisions? Previous
      studies conceptualize collective decision making using static combination rules,
      be it a majority-voting rule or a weighted-averaging rule. Unknown is whether
      groups adapt their combination rules to changing information environments. We
      implemented a novel paradigm for which information obeyed a mixture of
      distributions, such that the optimal Bayesian rule is nonlinear and often follows
      minority opinions, while the majority rule leads to suboptimal but above chance
      performance. Using perceptual (Experiment 1) and cognitive (Experiment 2) signal
      detection tasks, we switched the information environment halfway through the
      experiments to a mixture of distributions without informing participants. Groups
      gradually abandoned the majority rule to follow any minority opinion advocating
      signal presence with high confidence. Furthermore, groups with greater ability to
      abandon the majority rule achieved higher collective-decision accuracies. It is
      important to note that this abandonment was not triggered by performance loss for
      the majority rule relative to the first half of the experiment. Our results
      propose a new theory of human collective decision making: Humans make inferences
      about how information is distributed across individuals and time, and dynamically
      alter their joint decision algorithms to enhance the benefits of collective
      wisdom.

PMID- 26214503
TI  - When aging does not increase distraction: Evidence from pure auditory and visual
      oddball tasks.
AB  - Past research indicates that age increases deviance distraction in cross-modal
      oddball tasks, but results are few and less conclusive in purely auditory oddball
      tasks, with 3 studies not reporting age-related increase in deviance distraction
      against 1 that did (d = 1.04). This study aimed to (a) examine the effect of age
      on deviance distraction using the largest sample size to date to ensure adequate
      statistical power and (b) extend the study of same-modality deviance distraction
      to the visual modality. We compared 42 young and 42 older adults in auditory and
      visual duration discrimination tasks in which stimuli were presented with rare
      and unexpected task-irrelevant changes in pitch (in the auditory task) or
      location (in the visual task). The statistical power of our experiment to detect
      an effect size (d) of 1.04 was .999. Our results showed deviance distraction
      (longer response times for deviant stimuli than for standard stimuli) in both
      modalities. Importantly, these effects did not vary with age. Strong support for
      the absence of age-related variation in deviance distraction was further
      demonstrated by Bayes factor analysis. We conclude that aging does not appear to
      increase behavioral distraction by deviant stimuli in same-modality oddball
      tasks.

PMID- 26214504
TI  - Defusing Complexity in Intermetallics: How Covalently Shared Electron Pairs
      Stabilize the FCC Variant Mo2Cu(x)Ga(6-x) (x ~ 0.9).
AB  - Simple sphere packings of metallic atoms are generally assumed to exhibit highly
      delocalized bonding, often visualized in terms of a lattice of metal cations
      immersed in an electron gas. In this Article, we present a compound that
      demonstrates how covalently shared electron pairs can, in fact, play a key role
      in the stability of such structures: Mo2Cu(x)Ga(6-x) (x ~ 0.9). Mo2Cu(x)Ga(6-x)
      adopts a variant of the common TiAl3 structure type, which itself is a binary
      coloring of the fcc lattice. Electronic structure calculations trace the
      formation of this compound to a magic electron count of 14 electrons/T atom (T =
      transition metal) for the TiAl3 type, for which the Fermi energy coincides with
      an electronic pseudogap. This count is one electron/T atom lower than the
      electron concentration for a hypothetical MoGa3 phase, making this structure less
      competitive relative to more complex alternatives. The favorable 14 electron
      count can be reached, however, through the partial substitution of Ga with Cu.
      Using DFT-calibrated Huckel calculations and the reversed approximation Molecular
      Orbital (raMO) method, we show that the favorability of the 14 electron count has
      a simple structural origin in terms of the 18 - n rule of T-E intermetallics (E =
      main group element): the T atoms of the TiAl3 type are arranged into square nets
      whose edges are bridged by E atoms. The presence of shared electron pairs along
      these T-T contacts allows for 18 electron configurations to be achieved on the T
      atoms despite possessing only 18 - 4 = 14 electrons/T atom. This bonding scheme
      provides a rationale for the observed stability range of TiAl3 type TE3 phases of
      ca. 13-14 electrons/T atom, and demonstrates how the concept of the covalent bond
      can extend even to the most metallic of structure types.

PMID- 26214505
TI  - Anti-NeuGcGM3 reactivity: a possible role of natural antibodies and B-1 cells in
      tumor immunosurveillance.
AB  - While not naturally expressed in normal human tissues, N-glycolylated (NeuGc)
      gangliosides are overexpressed in several tumors and have immunosuppressive
      capacity, which contributes to cancer progression. Naturally occurring antibodies
      against NeuGcGM3 exist in healthy donors that specifically recognize and kill
      tumor cells expressing the antigen by complement-dependent and -independent
      mechanisms, the latter resembling an oncotic necrosis-type of cell death. Both
      the levels of anti-NeuGcGM3 antibodies in the sera of healthy donors and the
      percentage of donors with these natural antibodies decrease with age. Our work
      has shown that anti-NeuGcGM3 antibodies are not detected in the sera of non-small
      cell lung cancer (NSCLC) patients, compared to age- and sex-matched healthy
      donors, which have anti-NeuGcGM3. Interestingly, the level of serum total IgM,
      but not IgG, was significantly lower in cancer patients than in healthy donors.
      Screening of immortalized mouse splenic and peritoneal-derived hybridomas showed
      that peritoneal B-1 cells secrete anti-NeuGcGM3 with tumor cytotoxic capacity.
      Defects in the natural surveillance against tumor antigens could increase the
      risk of elderly donors developing cancer and affect the capacity of cancer
      patients to effectively fight against tumor cells. 

PMID- 26214506
TI  - Probing the coordination environment of Ti(3+) ions coordinated to nitrogen
      containing Lewis bases.
AB  - Multi-frequency continuous-wave and pulsed EPR techniques are employed to
      investigate the coordination of nitrogen-containing ligands to Ti(3+)-chloro
      complexes. Frozen solutions of TiCl3 and TiCl3(Py)3 dissolved in nitrogen
      containing solvents have been investigated together with the TiCl3(Py)3 solid
      state complex. For these different systems, the hyperfine and nuclear quadrupole
      data of Ti(3+)-bound (14)N nuclei are reported and discussed in the light of DFT
      computations, allowing for a detailed description of the microscopic structure of
      these systems. 

PMID- 26214507
TI  - Ready Access to Proquinazid Haptens via Cross-Coupling Chemistry for Antibody
      Generation and Immunoassay Development.
AB  - Bioconjugate preparation is a fundamental step for antibody generation and
      immunoassay development to small chemical compounds. For analytical targets
      holding in their structure an aryl halogen atom, cross-coupling reactions may be
      a simple and efficient way to obtain functionalized derivatives; thus offering
      great potential to elicit robust and selective immune responses after being
      coupled to immunogenic carrier proteins. However, substitution of the halogen
      atom by an aliphatic chain might eventually compromise the affinity and
      specificity of the resulting antibodies. In order to address this issue,
      proquinazid, a new-generation fungicide with outstanding performance, was chosen
      as model analyte. Two functionalized derivatives differing in spacer arm rigidity
      were synthesized by Sonogashira cross-coupling chemistry. These haptens were
      covalently coupled to bovine serum albumin and the resulting immunoconjugates
      were employed for rabbit vaccination. Antibodies were tested for proquinazid
      recognition by direct and indirect competitive immunoassay, and IC50 values in
      the low nanomolar range were found, thus demonstrating the suitability of this
      straightforward synthetic strategy for the generation of immunoreagents to
      compounds bearing an aryl halide. Following antibody characterization,
      competitive immunoassays were developed and employed to determine proquinazid
      residues in grape musts, and their analytical performance was satisfactorily
      validated by comparison with GC-MS. Besides having described the development of
      the first immunochemical method for proquinazid analysis, an efficient
      functionalization approach for analytes comprising aryl halides is reported. 

PMID- 26214508
TI  - Monocyte Chemoattractant Protein-Induced Protein 1 (MCPIP1) Enhances Angiogenic
      and Cardiomyogenic Potential of Murine Bone Marrow-Derived Mesenchymal Stem
      Cells.
AB  - The current evidence suggests that beneficial effects of mesenchymal stem cells
      (MSCs) toward myocardial repair are largely due to paracrine actions of several
      factors. Although Monocyte chemoattractant protein-induced protein 1 (MCPIP1) is
      involved in the regulation of inflammatory response, apoptosis and angiogenesis,
      whether MCPIP1 plays any role in stem cell-induced cardiac repair has never been
      examined. By employing retroviral (RV)-transduced overexpression of MCPIP1, we
      investigated the impact of MCPIP1 on viability, apoptosis, proliferation,
      metabolic activity, proteome, secretome and differentiation capacity of murine
      bone marrow (BM) - derived MSCs. MCPIP1 overexpression enhanced angiogenic and
      cardiac differentiation of MSCs compared with controls as indicated by elevated
      expression of genes accompanying angiogenesis and cardiomyogenesis in vitro. The
      proangiogenic activity of MCPIP1-overexpressing MSCs (MCPIP1-MSCs) was also
      confirmed by increased capillary-like structure formation under several culture
      conditions. This increase in differentiation capacity was associated with
      decreased proliferation of MCPIP1-MSCs when compared with controls. MCPIP1-MSCs
      also expressed increased levels of proteins involved in angiogenesis, autophagy,
      and induction of differentiation, but not adverse inflammatory agents. We
      conclude that MCPIP1 enhances endothelial and cardiac differentiation of MSCs.
      Thus, modulating MCPIP1 expression may be a novel approach useful for enhancing
      the immune-regulatory, anti-apoptotic, anti-inflammatory and regenerative
      capacity of BM-derived MSCs for myocardial repair and regeneration of ischemic
      tissues. 

PMID- 26214509
TI  - Beech Fructification and Bank Vole Population Dynamics--Combined Analyses of
      Promoters of Human Puumala Virus Infections in Germany.
AB  - The transmission of wildlife zoonoses to humans depends, amongst others, on
      complex interactions of host population ecology and pathogen dynamics within host
      populations. In Europe, the Puumala virus (PUUV) causes nephropathia epidemica in
      humans. In this study we investigated complex interrelations within the epidemic
      system of PUUV and its rodent host, the bank vole (Myodes glareolus). We suggest
      that beech fructification and bank vole abundance are both decisive factors
      affecting human PUUV infections. While rodent host dynamics are expected to be
      directly linked to human PUUV infections, beech fructification is a rather
      indirect predictor by serving as food source for PUUV rodent hosts. Furthermore,
      we examined the dependence of bank vole abundance on beech fructification. We
      analysed a 12-year (2001-2012) time series of the parameters: beech
      fructification (as food resource for the PUUV host), bank vole abundance and
      human incidences from 7 Federal States of Germany. For the first time, we could
      show the direct interrelation between these three parameters involved in human
      PUUV epidemics and we were able to demonstrate on a large scale that human PUUV
      infections are highly correlated with bank vole abundance in the present year, as
      well as beech fructification in the previous year. By using beech fructification
      and bank vole abundance as predictors in one model we significantly improved the
      degree of explanation of human PUUV incidence. Federal State was included as
      random factor because human PUUV incidence varies considerably among states.
      Surprisingly, the effect of rodent abundance on human PUUV infections is less
      strong compared to the indirect effect of beech fructification. Our findings are
      useful to facilitate the development of predictive models for host population
      dynamics and the related PUUV infection risk for humans and can be used for plant
      protection and human health protection purposes. 

PMID- 26214510
TI  - Maternal Smoking History Enhances the Expression of Placental Growth Factor in
      Invasive Trophoblasts at Early Gestation Despite Cessation of Smoking.
AB  - Maternal smoking during early pregnancy is associated with a reduced risk for
      preeclampsia even after smoking cessation during pregnancy. Although the
      pathophysiology of preeclampsia has not been established, placental growth factor
      (PlGF) is believed to be a key factor. The aim of this study was to assess the
      effect of maternal smoking on the PlGF expression in invasive trophoblasts at
      early gestation. We collected villous tissues from women requesting surgical
      termination due to non-medical reasons at 7-8 weeks of gestation. The maternal
      smoking status was evaluated by measuring the serum cotinine level and patients
      were divided into two groups: active smokers and non-smokers. After separating
      invasive trophoblasts from villous tissues cultured initially under 2% O2 for 24
      hours, the separated invasive trophoblasts were cultured under 2% or 8% O2 for 48
      hours. The expression levels of the PlGF gene in villous tissue specimens and in
      invasive trophoblasts cultured after the conditions were quantified using qRT
      PCR. The levels of PlGF protein in the medium were quantified using an ELISA. The
      gene expression level of PlGF in the villi in the active-smokers was
      significantly higher than that of the non-smokers. In comparison of the invasive
      trophoblasts under normoxia and oxygenated conditions, the ratio of PlGF gene
      expression and protein expression under oxygenation (2% O2+8% O2 / 2% O2+2% O2)
      in the active-smokers were both significantly higher than in the non-smokers.
      Maternal smoking history appears to stimulate PlGF expression in invasive
      trophoblasts under oxygenated conditions. This may be one of several causes
      leading to the protective effect of maternal smoking on preeclampsia. 

PMID- 26214511
TI  - Frequency and Severity of Parenteral Nutrition Medication Errors at a Large
      Children's Hospital After Implementation of Electronic Ordering and Compounding.
AB  - INTRODUCTION: The Institute for Safe Medication Practices has stated that
      parenteral nutrition (PN) is considered a high-risk medication and has the
      potential of causing harm. Three organizations--American Society for Parenteral
      and Enteral Nutrition (A.S.P.E.N.), American Society of Health-System
      Pharmacists, and National Advisory Group--have published guidelines for ordering,
      transcribing, compounding and administering PN. These national organizations have
      published data on compliance to the guidelines and the risk of errors. The
      purpose of this article is to compare total compliance with ordering,
      transcription, compounding, administration, and error rate with a large pediatric
      institution. METHOD: A computerized prescriber order entry (CPOE) program was
      developed that incorporates dosing with soft and hard stop recommendations and
      simultaneously eliminating the need for paper transcription. A CPOE team
      prioritized and identified issues, then developed solutions and integrated
      innovative CPOE and automated compounding device (ACD) technologies and practice
      changes to minimize opportunities for medication errors in PN prescription,
      transcription, preparation, and administration. Thirty developmental processes
      were identified and integrated in the CPOE program, resulting in practices that
      were compliant with A.S.P.E.N. safety consensus recommendations. Data from 7
      years of development and implementation were analyzed and compared with published
      literature comparing error, harm rates, and cost reductions to determine if our
      process showed lower error rates compared with national outcomes. RESULTS: The
      CPOE program developed was in total compliance with the A.S.P.E.N. guidelines for
      PN. The frequency of PN medication errors at our hospital over the 7 years was
      230 errors/84,503 PN prescriptions, or 0.27% compared with national data that
      determined that 74 of 4730 (1.6%) of prescriptions over 1.5 years were associated
      with a medication error. Errors were categorized by steps in the PN process:
      prescribing, transcription, preparation, and administration. There were no
      transcription errors, and most (95%) errors occurred during administration.
      CONCLUSION: We conclude that PN practices that conferred a meaningful cost
      reduction and a lower error rate (2.7/1000 PN) than reported in the literature
      (15.6/1000 PN) were ascribed to the development and implementation of practices
      that conform to national PN guidelines and recommendations. Electronic ordering
      and compounding programs eliminated all transcription and related opportunities
      for errors.

PMID- 26214512
TI  - Experience in Bedside Placement, Clinical Validity, and Cost-Efficacy of a Self
      Propelled Nasojejunal Feeding Tube.
AB  - BACKGROUND: The procedures needed to insert nasojejunal tubes (NJTs) are often
      invasive or uncomfortable for the patient and require hospital resources. The
      objectives of this study were to describe our experience in inserting a self
      propelling NJT with distal pigtail end and evaluate clinical validity and cost
      efficacy of this enteral nutrition (EN) approach compared with parenteral
      nutrition (PN). MATERIALS AND METHODS: Prospective study from July 2009 to
      December 2010, including hospitalized noncritical patients who required short
      term jejunal EN. The tubes were inserted at bedside, using intravenous
      erythromycin as a prokinetic drug. Positioning was considered correct when the
      distal end was beyond the ligament of Treitz. Migration failure was considered
      when the tube was not positioned into the jejunum within 48 hours postinsertion.
      RESULTS: Fifty-six insertions were recorded in 47 patients, most frequently in
      severe acute pancreatitis (69.6%). The migration rates at 18 and 48 hours
      postinsertion were 73.2% and 82.1%, respectively. There was migration failure in
      8.9% of cases, and 8.9% were classified null (the tube was no longer in the
      gastrointestinal tract at 18 hours). There were no reported or observed
      complications. The mean duration of the EN was 12 +/- 10.8 days. Five different
      types of EN formula were used. The total study cost was 53.9% lower compared with
      using PN in all patients. CONCLUSIONS: Our study demonstrated that bedside
      insertion of a self-propelling NJT is a safe, cost-effective, and successful
      technique for postpyloric enteral feeding in at least 73% of the patients, and
      only 18% of patients could eventually need other placement techniques. It can
      avoid the need for more aggressive or expensive placement techniques or even PN
      if we cannot achieve enteral access.

PMID- 26214513
TI  - Pneumococal Surface Protein A (PspA) Regulates Programmed Death Ligand 1
      Expression on Dendritic Cells in a Toll-Like Receptor 2 and Calcium Dependent
      Manner.
AB  - Pneumonia leads to high mortality in children under the age of five years
      worldwide, resulting in close to 20 percent of all deaths in this age group.
      Therefore, investigations into host-pathogen interactions during Streptococcus
      pneumoniae infection are key in devising strategies towards the development of
      better vaccines and drugs. To that end, in this study we investigated the role of
      S. pneumoniae and its surface antigen Pneumococcal surface protein A (PspA) in
      modulating the expression of co-stimulatory molecule Programmed Death Ligand 1
      (PD-L1) expression on dendritic cells (DCs) and the subsequent effects of
      increased PD-L1 on key defence responses. Our data indicate that stimulation of
      DCs with PspA increases the surface expression of PD-L1 in a time and dose
      dependent manner. Characterization of mechanisms involved in PspA induced
      expression of PD-L1 indicate the involvement of Toll-Like Receptor 2 (TLR2) and
      calcium homeostasis. While calcium release from intracellular stores positively
      regulated PD-L1 expression, calcium influx from external milieu negatively
      regulated PD-L1 expression. Increase in PD-L1 expression, when costimulated with
      PspA and through TLR2 was higher than when stimulated with PspA or through TLR2.
      Further, knockdown of TLR2 and the intermediates in the TLR signaling machinery
      pointed towards the involvement of a MyD88 dependent pathway in PspA induced PD
      L1 expression. Incubation of DCs with S. pneumoniae resulted in the up-regulation
      of PD-L1 expression, while infection with a strain lacking surface PspA failed to
      do so. Our data also suggests the role of PspA in ROS generation. These results
      suggest a novel and specific role for PspA in modulating immune responses against
      S. pneumoniae by regulating PD-L1 expression. 

PMID- 26214514
TI  - Study of the BCG Vaccine-Induced Cellular Immune Response in Schoolchildren in
      Antananarivo, Madagascar.
AB  - OBJECTIVE: Although the Bacillus Calmette-Guerin vaccine (BCG) protects young
      children against serious forms of TB, protection against pulmonary TB is
      variable. We assessed BCG vaccine-induced cellular immune responses and
      determined for how long they could be detected during childhood in Antananarivo,
      Madagascar. METHODS: We assessed BCG vaccine-induced cellular immune responses by
      TST and IGRA (in-house ELISPOT assay) using BCG and PPD as stimulation antigen,
      and compared results between vaccinated and non-vaccinated schoolchildren of two
      age groups, 6-7 and 13-14 years old. RESULTS: Three hundred and sixty-three
      healthy schoolchildren were enrolled. TST was performed on 351 children and IGRA
      on 142. A high proportion (66%; 229/343) of the children had no TST reactivity
      (induration size 0 mm). TST-positive responses (>=15 mm) were more prevalent
      among 13-14 year-old (31.7%) than 6-7 year old (16.5%) children, both in the non
      vaccinated (43% vs. 9%, p<0.001) and vaccinated (29% vs. 13%, p=0.002) subgroups.
      There were no significant differences in TST responses between vaccinated and non
      vaccinated children in either of the age groups. The IGRA response to BCG and to
      PPD stimulation was not significantly different according to BCG vaccination
      record or to age group. A high rate (15.5%; 22/142) of indeterminate IGRA
      responses was observed. There was very poor agreement between TST and IGRA-PPD
      findings (k= 0.08) and between TST and IGRA-BCG findings (k= 0.02). CONCLUSION:
      Analysis of TST and IGRA response to stimulation with BCG and PPD revealed no
      difference in immune response between BCG-vaccinated and non-vaccinated children;
      also no decrease of the BCG vaccine-induced cellular immune response over time
      was observed. We conclude that TST and IGRA have limitations in assessing a role
      of BCG or tuberculosis-related immunity.

PMID- 26214515
TI  - A Quantitative Analysis of Undisclosed Conflicts of Interest in Pharmacology
      Textbooks.
AB  - BACKGROUND: Disclosure of potential conflicts of interest (CoI) is a standard
      practice for many biomedical journals but not for educational materials. The goal
      of this investigation was to determine whether the authors of pharmacology
      textbooks have undisclosed financial CoIs and to identify author characteristics
      associated with CoIs. METHODS AND FINDINGS: The presence of potential CoIs was
      evaluated by submitting author names (N = 403; 36.3% female) to a patent database
      (Google Scholar) as well as a database that reports on the compensation ($USD)
      received from 15 pharmaceutical companies (ProPublica's Dollars for Docs). All
      publications (N = 410) of the ten highest compensated authors from 2009 to 2013
      and indexed in Pubmed were also examined for disclosure of additional companies
      that the authors received research support, consulted, or served on speaker's
      bureaus. A total of 134 patents had been awarded (Maximum = 18/author) to
      textbook authors. Relative to DiPiro's Pharmacotherapy: A Pathophysiologic
      Approach, contributors to Goodman and Gilman's Pharmacological Basis of
      Therapeutics and Katzung's Basic and Clinical Pharmacology were more frequently
      patent holders (OR = 6.45, P < .0005). Female authors were less likely than males
      to have > 1 patent (OR = 0.15, P < .0005). A total of $2,411,080 USD (28.3% for
      speaking, 27.0% for consulting, and 23.9% for research), was received by 53
      authors (Range = $299 to $310,000/author). Highly compensated authors were from
      multiple fields including oncology, psychiatry, neurology, and urology. The
      maximum number of additional companies, not currently indexed in the Dollars for
      Docs database, for which an author had potential CoIs was 73. CONCLUSIONS:
      Financial CoIs are common among the authors of pharmacology and pharmacotherapy
      textbooks. Full transparency of potential CoIs, particularly patents, should
      become standard procedure for future editions of educational materials in
      pharmacology.

PMID- 26214516
TI  - Early Mortality during Initial Treatment of Tuberculosis in Patients Co-Infected
      with HIV at the Yaounde Central Hospital, Cameroon: An 8-Year Retrospective
      Cohort Study (2006-2013).
AB  - BACKGROUND: Understanding contributors to mortality during the initial phase of
      tuberculosis (TB) treatment in patients co-infected with HIV would guide targeted
      interventions to improve survival. The aim of this study was to ascertain the
      incidence of death during the initial 2 months (new cases) and 3 months
      (retreatment cases) of TB treatment and to assess correlates of mortality in HIV
      co-infected patients. METHODS: We conducted a hospital-based retrospective cohort
      study from January 2006 to December 2013 at Yaounde Central Hospital, Cameroon.
      We reviewed medical records to identify co-infected TB/HIV inpatients aged 15
      years and older who died during TB treatment. Death was defined as any death
      occurring during TB treatment, as per World Health Organization recommendations.
      We collected socio-demographic, clinical and laboratory data. We conducted
      multivariable logistic binary regression analysis to identify factors associated
      with death during the intensive phase of TB treatment. Magnitudes of associations
      were expressed by adjusted odds ratio (aOR) with 95% confidence interval. A p
      value < 0.05 was considered statistically significant. RESULTS: The 99 patients
      enrolled had a mean age of 39.5 (standard deviation 10.9) years and 53% were
      male. Patients were followed for 276.3 person-months of observation (PMO). Forty
      nine patients were died during intensive phase of TB treatment. Death incidence
      during the intensive phase of TB treatment was 32.2 per 100 PMO. Having a non
      AIDS comorbidity (aOR 2.47, 95%CI 1.22-5.02, p = 0.012), having extra-pulmonary
      TB (aOR 1.89, 95%CI 1.05-3.43, p = 0.035), and one year increase in duration of
      known HIV infection (aOR 1.23, 95%CI 1.004-1.49) were independently associated
      with death during the intensive phase of TB treatment. CONCLUSIONS: Mortality
      incidence during intensive phase of TB treatment was high among TB/HIV co
      infected patients during TB treatment; and strongly associated with extra
      pulmonary TB suggesting advanced stage of immunosuppression and non-AIDS
      comorbidities. Early HIV diagnosis and care and good management of non
      comorbidities can reduce this incidence.

PMID- 26214517
TI  - PDIA3 Knockdown Exacerbates Free Fatty Acid-Induced Hepatocyte Steatosis and
      Apoptosis.
AB  - Nonalcoholic fatty liver disease (NAFLD) has emerged as one of the most common
      chronic liver disease over the past decades. Endoplasmic reticulum stress (ERS)
      plays a pivotal role during the development of NAFLD. This study aims to analyze
      the potential role of protein disulfide isomerase A3 precursor (PDIA3), one of
      the ER chaperones, in free fatty acid-induced cell model of NAFLD. Human liver
      L02 cell line was treated with sodium palmitate for 24 hours, which developed
      severe intracellular lipid accumulation. The increased protein level of PDIA3 was
      detected via immunoblotting analysis in the fat loaded cell models of NAFLD.
      siRNA-mediated knockdown of PDIA3 in L02 cells not only increased the cellular
      lipid accumulation, but also exacerbated hepatocytes apoptosis induced by sodium
      palmitate. Further investigation revealed that knockdown of PDIA3 up-regulated
      protein expression of fatty acid synthase (FAS), a key enzyme involved in fatty
      acid synthesis. PDIA3 knockdown also up-regulated key molecules of ERS pathway,
      including glucose-regulated protein 78 (GRP78), phospho-PKR-like ER kinase (p
      PERK), and C/EBP homologous protein (CHOP). Our results suggested that ER
      chaperone PDIA3 plays a pivotal role in FFA-induced hepatocyte steatosis and
      apoptosis. 

PMID- 26214518
TI  - Lymphatic vessel development: fluid flow and valve-forming cells.
AB  - Hemodynamic forces regulate many aspects of blood vessel disease and development,
      including susceptibility to atherosclerosis and remodeling of primary blood
      vessels into a mature vascular network. Vessels of the lymphatic circulatory
      system are also subjected to fluid flow-associated forces, but the molecular and
      cellular mechanisms by which these forces regulate the formation and maintenance
      of lymphatic vessels remain largely uncharacterized. This issue of the JCI
      includes two articles that begin to address how fluid flow influences lymphatic
      vessel development and function. Sweet et al. demonstrate that lymph flow is
      essential for the remodeling of primary lymphatic vessels, for ensuring the
      proper distribution of smooth muscle cells (SMCs), and for the development and
      maturation of lymphatic valves. Kazenwadel et al. show that flow-induced
      lymphatic valve development is initiated by the upregulation of GATA2, which has
      been linked to lymphedema in patients with Emberger syndrome. Together, these
      observations and future studies inspired by these results have potential to lead
      to the development of strategies for the treatment of lymphatic disorders. 

PMID- 26214519
TI  - Emerging roles for macrophages in cardiac injury: cytoprotection, repair, and
      regeneration.
AB  - The mammalian heart contains a population of resident macrophages that expands in
      response to myocardial infarction through the recruitment of monocytes. Infarct
      macrophages exhibit high phenotypic diversity and respond to microenvironmental
      cues by altering their functional properties and secretory profile. In this issue
      of the JCI, de Couto and colleagues demonstrate that infiltrating macrophages can
      be primed to acquire a cardioprotective phenotype in ischemic heart and exert
      this proactive effect through activation of an antiapoptotic program in
      cardiomyocytes. This study supports the growing body of evidence that suggests
      that macrophage subpopulations can be modulated to mediate cytoprotective,
      reparative, and even regenerative functions in the infarcted heart. The cellular
      mechanisms and molecular signals driving these macrophage phenotypes are yet
      unknown; however, harnessing the remarkable potential of the macrophage in
      regulating cell survival and tissue regeneration may hold therapeutic promise for
      myocardial infarction. 

PMID- 26214520
TI  - PTP1B: a new therapeutic target for Rett syndrome.
AB  - Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that is
      characterized by successive loss of acquired cognitive, social, and motor skills
      and development of autistic behavior. RTT affects approximately 1 in 10,000 live
      female births and is the second most common cause of severe mental retardation in
      females, after Down syndrome. Currently, there is no cure or effective therapy
      for RTT. Approved treatment regimens are presently limited to supportive
      management of specific physical and mental disabilities. In this issue, Krishnan
      and colleagues reveal that the protein tyrosine phosphatase PTP1B is upregulated
      in patients with RTT and in murine models and provide strong evidence that
      targeting PTP1B has potential as a viable therapeutic strategy for the treatment
      of RTT. 

PMID- 26214521
TI  - Therapeutic cancer vaccines.
AB  - The clinical benefit of therapeutic cancer vaccines has been established. Whereas
      regression of lesions was shown for premalignant lesions caused by HPV, clinical
      benefit in cancer patients was mostly noted as prolonged survival. Suboptimal
      vaccine design and an immunosuppressive cancer microenvironment are the root
      causes of the lack of cancer eradication. Effective cancer vaccines deliver
      concentrated antigen to both HLA class I and II molecules of DCs, promoting both
      CD4 and CD8 T cell responses. Optimal vaccine platforms include DNA and RNA
      vaccines and synthetic long peptides. Antigens of choice include mutant
      sequences, selected cancer testis antigens, and viral antigens. Drugs or physical
      treatments can mitigate the immunosuppressive cancer microenvironment and include
      chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors,
      inhibitors of T cell checkpoints, agonists of selected TNF receptor family
      members, and inhibitors of undesirable cytokines. The specificity of therapeutic
      vaccination combined with such immunomodulation offers an attractive avenue for
      the development of future cancer therapies. 

PMID- 26214522
TI  - PTP1B inhibition suggests a therapeutic strategy for Rett syndrome.
AB  - The X-linked neurological disorder Rett syndrome (RTT) presents with autistic
      features and is caused primarily by mutations in a transcriptional regulator,
      methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are
      limited to alleviating some neurological symptoms; hence, more effective
      therapeutic strategies are needed. We identified the protein tyrosine phosphatase
      PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the
      PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of
      MECP2 function was associated with increased levels of PTP1B in RTT models.
      Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption
      in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice
      and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated
      that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine
      kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF).
      Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in
      RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased
      tyrosine phosphorylation of TRKB in the brain, which would augment BDNF
      signaling. This study presents PTP1B as a mechanism-based therapeutic target for
      RTT, validating a unique strategy for treating the disease by modifying signal
      transduction pathways with small-molecule drugs. 

PMID- 26214523
TI  - Lymph flow regulates collecting lymphatic vessel maturation in vivo.
AB  - Fluid shear forces have established roles in blood vascular development and
      function, but whether such forces similarly influence the low-flow lymphatic
      system is unknown. It has been difficult to test the contribution of fluid forces
      in vivo because mechanical or genetic perturbations that alter flow often have
      direct effects on vessel growth. Here, we investigated the functional role of
      flow in lymphatic vessel development using mice deficient for the platelet
      specific receptor C-type lectin-like receptor 2 (CLEC2) as blood backfills the
      lymphatic network and blocks lymph flow in these animals. CLEC2-deficient animals
      exhibited normal growth of the primary mesenteric lymphatic plexus but failed to
      form valves in these vessels or remodel them into a structured, hierarchical
      network. Smooth muscle cell coverage (SMC coverage) of CLEC2-deficient lymphatic
      vessels was both premature and excessive, a phenotype identical to that observed
      with loss of the lymphatic endothelial transcription factor FOXC2. In vitro
      evaluation of lymphatic endothelial cells (LECs) revealed that low, reversing
      shear stress is sufficient to induce expression of genes required for lymphatic
      valve development and identified GATA2 as an upstream transcriptional regulator
      of FOXC2 and the lymphatic valve genetic program. These studies reveal that lymph
      flow initiates and regulates many of the key steps in collecting lymphatic vessel
      maturation and development. 

PMID- 26214524
TI  - Helicobacter urease-induced activation of the TLR2/NLRP3/IL-18 axis protects
      against asthma.
AB  - Inflammasome activation and caspase-1-dependent (CASP1-dependent) processing and
      secretion of IL-1beta and IL-18 are critical events at the interface of the
      bacterial pathogen Helicobacter pylori with its host. Whereas IL-1beta promotes
      Th1 and Th17 responses and gastric immunopathology, IL-18 is required for Treg
      differentiation, H. pylori persistence, and protection against allergic asthma,
      which is a hallmark of H. pylori-infected mice and humans. Here, we show that
      inflammasome activation in DCs requires the cytoplasmic sensor NLRP3 as well as
      induction of TLR2 signaling by H. pylori. Screening of an H. pylori transposon
      mutant library revealed that pro-IL-1beta expression is induced by LPS from H.
      pylori, while the urease B subunit (UreB) is required for NLRP3 inflammasome
      licensing. UreB activates the TLR2-dependent expression of NLRP3, which
      represents a rate-limiting step in NLRP3 inflammasome assembly. ureB-deficient H.
      pylori mutants were defective for CASP1 activation in murine bone marrow-derived
      DCs, splenic DCs, and human blood-derived DCs. Despite colonizing the murine
      stomach, ureB mutants failed to induce IL-1beta and IL-18 secretion and to
      promote Treg responses. Unlike WT H. pylori, ureB mutants were incapable of
      conferring protection against allergen-induced asthma in murine models. Together,
      these results indicate that the TLR2/NLRP3/CASP1/IL-18 axis is critical to H.
      pylori-specific immune regulation.

PMID- 26214525
TI  - GATA2 is required for lymphatic vessel valve development and maintenance.
AB  - Heterozygous germline mutations in the zinc finger transcription factor GATA2
      have recently been shown to underlie a range of clinical phenotypes, including
      Emberger syndrome, a disorder characterized by lymphedema and predisposition to
      myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). Despite well-defined
      roles in hematopoiesis, the functions of GATA2 in the lymphatic vasculature and
      the mechanisms by which GATA2 mutations result in lymphedema have not been
      characterized. Here, we have provided a molecular explanation for lymphedema
      predisposition in a subset of patients with germline GATA2 mutations.
      Specifically, we demonstrated that Emberger-associated GATA2 missense mutations
      result in complete loss of GATA2 function, with respect to the capacity to
      regulate the transcription of genes that are important for lymphatic vessel valve
      development. We identified a putative enhancer element upstream of the key
      lymphatic transcriptional regulator PROX1 that is bound by GATA2, and the
      transcription factors FOXC2 and NFATC1. Emberger GATA2 missense mutants had a
      profoundly reduced capacity to bind this element. Conditional Gata2 deletion in
      mice revealed that GATA2 is required for both development and maintenance of
      lymphovenous and lymphatic vessel valves. Together, our data unveil essential
      roles for GATA2 in the lymphatic vasculature and explain why a select catalogue
      of human GATA2 mutations results in lymphedema. 

PMID- 26214526
TI  - Fibrinolysis is essential for fracture repair and prevention of heterotopic
      ossification.
AB  - Bone formation during fracture repair inevitably initiates within or around
      extravascular deposits of a fibrin-rich matrix. In addition to a central role in
      hemostasis, fibrin is thought to enhance bone repair by supporting inflammatory
      and mesenchymal progenitor egress into the zone of injury. However, given that a
      failure of efficient fibrin clearance can impede normal wound repair, the precise
      contribution of fibrin to bone fracture repair, whether supportive or
      detrimental, is unknown. Here, we employed mice with genetically and
      pharmacologically imposed deficits in the fibrin precursor fibrinogen and fibrin
      degrading plasminogen to explore the hypothesis that fibrin is vital to the
      initiation of fracture repair, but impaired fibrin clearance results in
      derangements in bone fracture repair. In contrast to our hypothesis, fibrin was
      entirely dispensable for long-bone fracture repair, as healing fractures in
      fibrinogen-deficient mice were indistinguishable from those in control animals.
      However, failure to clear fibrin from the fracture site in plasminogen-deficient
      mice severely impaired fracture vascularization, precluded bone union, and
      resulted in robust heterotopic ossification. Pharmacological fibrinogen depletion
      in plasminogen-deficient animals restored a normal pattern of fracture repair and
      substantially limited heterotopic ossification. Fibrin is therefore not essential
      for fracture repair, but inefficient fibrinolysis decreases endochondral
      angiogenesis and ossification, thereby inhibiting fracture repair. 

PMID- 26214529
TI  - Ocular Graft-Versus-Host Disease: A Review.
AB  - Hematopoietic stem cell transplantation is important in the management of several
      lymphoproliferative and bone marrow disorders. Graft-versus-host disease (GVHD)
      involves inflammatory manifestations that arise after transplant and can affect
      many organs. Ocular manifestations of GVHD are common, and eye care providers
      must understand this disease entity. The ocular surface is most commonly
      involved, but GVHD can affect all parts of the eye. Ocular GVHD can be relapsing
      and remitting, can decrease quality of life, and can be challenging to diagnose
      and adequately treat. The diagnostic criteria for and grading of ocular GVHD
      continue to evolve. This review aims to summarize current definitions, clinical
      findings, diagnostic criteria, and management of ocular GVHD. The care of
      patients with ocular GVHD requires a multidisciplinary approach. 

PMID- 26214527
TI  - Macrophages mediate cardioprotective cellular postconditioning in acute
      myocardial infarction.
AB  - Ischemic injury in the heart induces an inflammatory cascade that both repairs
      damage and exacerbates scar tissue formation. Cardiosphere-derived cells (CDCs)
      are a stem-like population that is derived ex vivo from cardiac biopsies; they
      confer both cardioprotection and regeneration in acute myocardial infarction
      (MI). While the regenerative effects of CDCs in chronic settings have been
      studied extensively, little is known about how CDCs confer the cardioprotective
      process known as cellular postconditioning. Here, we used an in vivo rat model of
      ischemia/reperfusion (IR) injury-induced MI and in vitro coculture assays to
      investigate how CDCs protect stressed cardiomyocytes. Compared with control
      animals, animals that received CDCs 20 minutes after IR had reduced infarct size
      when measured at 48 hours. CDCs modified the myocardial leukocyte population
      after ischemic injury. Specifically, introduction of CDCs reduced the number of
      CD68+ macrophages, and these CDCs secreted factors that polarized macrophages
      toward a distinctive cardioprotective phenotype that was not M1 or M2. Systemic
      depletion of macrophages with clodronate abolished CDC-mediated cardioprotection.
      Using both in vitro coculture assays and a rat model of adoptive transfer after
      IR, we determined that CDC-conditioned macrophages attenuated cardiomyocyte
      apoptosis and reduced infarct size, thereby recapitulating the beneficial effects
      of CDC therapy. Together, our data indicate that CDCs limit acute injury by
      polarizing an effector macrophage population within the heart. 

PMID- 26214530
TI  - Use of Scleral Lenses and Miniscleral Lenses After Penetrating Keratoplasty.
AB  - PURPOSE: To examine the clinical outcomes of scleral lenses for visual
      rehabilitation after penetrating keratoplasty (PK). METHODS: A retrospective
      review was conducted for 34 patients (48 eyes) who had a history of prior PK and
      were fit with scleral lenses between October 2009 and December 2013 at the UC
      Davis Eye Center. RESULTS: The most common initial indication for PK was
      keratoconus in 27 eyes (56%). Thirty-three eyes (69%) had previously been fit
      with other types of contact lenses, with small-diameter rigid gas-permeable
      lenses being the most common. The improvement in best-corrected visual acuity
      with a scleral lens compared with prior spectacle refraction or other contact
      lens was a mean of two best-corrected visual acuity lines. Forty-four eyes
      (91.7%) achieved functional vision with best scleral lens-corrected visual
      acuities of 20/40 or better. Patients who continued wearing scleral lenses were
      significantly more likely to report "good" subjective vision compared with
      patients who abandoned scleral lens wear (P=0.009), although change in objective
      best-corrected visual acuity did not differ significantly. There were no cases of
      infectious keratitis. Six eyes (12.5%) developed graft rejection; 3 were able to
      resume scleral lens wear. Nineteen eyes (39.5%) discontinued scleral lens wear
      for various reasons, the most common reason for discontinuation of lens wear was
      difficulty with scleral lens insertion or removal (8 eyes, 42.1%). CONCLUSION:
      Scleral lenses are effective and safe in patients who have had PK. There was a
      mean gain in visual acuity, with the majority of patients achieving 20/40 vision
      or better. The patient's subjective perception of vision was a significant factor
      in determining whether scleral lens wear was continued or abandoned.

PMID- 26214528
TI  - Resilience, traumatic brain injury, depression, and posttraumatic stress among
      Iraq/Afghanistan war veterans.
AB  - OBJECTIVE: We examined the prospective influence of the resilient,
      undercontrolled, and overcontrolled personality prototypes on depression and
      posttraumatic stress disorder (PTSD) symptoms among Iraq/Afghanistan war
      veterans. After accounting for the possible influence of combat exposure, we
      expected that the resilient prototype would predict lower depression and PTSD
      over time and would be associated with adaptive coping strategies, higher social
      support, lower psychological inflexibility, and higher self-reported resilience
      relative to overcontrolled and undercontrolled prototypes, independent of
      traumatic brain injury (TBI) status. METHOD: One hundred twenty-seven veterans
      (107 men, 20 women; average age = 37) participated in the study. Personality was
      assessed at baseline, and PTSD and depression symptoms were assessed 8 months
      later. Path analysis was used to test the direct and indirect effects of
      personality on distress. RESULTS: No direct effects were observed from
      personality to distress. The resilient prototype did have significant indirect
      effects on PTSD and depression through its beneficial effects on social support,
      coping and psychological inflexibility. TBI also had direct effects on PTSD.
      CONCLUSIONS: A resilient personality prototype appears to influence veteran
      adjustment through its positive associations with greater social support and
      psychological flexibility, and lower use of avoidant coping. Low social support,
      avoidant coping, and psychological inflexibility are related to overcontrolled
      and undercontrolled personality prototypes, and these behaviors seem to
      characterize veterans who experience problems with depression and PTSD over time.
      A positive TBI status is directly and prospectively associated with PTSD
      symptomology independent of personality prototype. Implications for clinical
      interventions and future research are discussed.

PMID- 26214531
TI  - Drug augmented hepatobiliary scintigraphy for evaluation of neonatal cholestasis:
      what does the evidence point to?

PMID- 26214532
TI  - Drug-augmented hepatobiliary scintigraphy for evaluation of neonatal cholestasis:
      What does the evidence point to?

PMID- 26214533
TI  - News and Views--September 2015.

PMID- 26214534
TI  - Analyzing Cancer Disparities: A New Policy Landscape Calls for New Approaches to
      Research.

PMID- 26214535
TI  - National Trends and Disparities in Mammography Among Commercially Insured Women,
      2001-2010.
AB  - CONTEXT: Prior research suggests that mammography declined from 2000 to 2005 and
      that socioeconomic disparities remained wide. OBJECTIVE: To assess national
      trends and disparities in mammography among commercially insured women from 2001
      to 2010. DESIGN, SETTING, PARTICIPANTS: This study used a longitudinal time
      series design to examine mammography rates among 5.4 million US women aged 40 to
      64 years from 2001 to 2010. Adjusted annual rates stratified by age group (40-49
      years/50-64 years) and neighborhood-level socioeconomic characteristics including
      poverty and race/ethnicity were plotted. Mammography disparities were defined as
      the absolute percentage difference in adjusted screening rates between population
      subgroups in a given year. Trends in 2001-2010 screening rates and socioeconomic
      disparities were fitted as annual percentage changes (APCs) using join point
      analysis, which can determine changes in trends. MAIN OUTCOME MEASURE: Annual and
      biennial mammogram. RESULTS: Adjusted annual mammography rates among women aged
      40 to 49 years increased from 38.5% to 45.5% (0.78% APC, P < .001) over the
      decade. Among women aged 50 to 64 years, 2001-2004 rates decreased from 49.7% to
      47.4% (-0.78% APC, P = .035) and then increased to 51.8% by 2010 (APC of 0.80%, P
      < .001). Women aged 40 to 49 years had an unchanged high-low neighborhood poverty
      screening disparity of 11.0% over the decade (APC -0.05%, P = .508). The
      estimated white-black disparity decreased from 9.6% to 7.7% from 2001 to 2010 (
      0.21% APC, P = .042). The white-Hispanic disparity decreased from 9.6% to 6.2%
      between 2001 and 2003 (APC -1.69%, P = .143) and then to 5.3% by 2010 (APC 
      0.14%, P = .343). Among women aged 50 to 64 years, estimated high-low poverty and
      white-black disparities declined (11.0%-9.5% [-0.16% APC, P = .026] and 8.6%-6.3%
      [-0.26% APC, P = .008], respectively) while the white-Hispanic disparity
      decreased from 14.9% to 5.4% between 2001 and 2003 (-4.77% APC, P = .023) and was
      6.5% by 2010. CONCLUSIONS: Mammography increased among women aged 40 to 49 years
      from 2001 to 2010 and after 2004 among women aged 50 to 64 years. Women from
      black and Hispanic neighborhoods experienced reduced disparities, but disparities
      by poverty level changed little.

PMID- 26214536
TI  - Taking a Step Forward in Public Health Finance: Establishing Standards for a
      Uniform Chart of Accounts Crosswalk.
AB  - In its 2012 report on the current and future states of public health finance, the
      Institute of Medicine noted, with concern, the relative lack of capacity for
      practitioners and researchers alike to make comparisons between health department
      expenditures across the country. This is due in part to different accounting
      systems, service portfolios, and state- or agency-specific reporting
      requirements. The Institute of Medicine called for a uniform chart of accounts,
      perhaps building on existing efforts such as the Public Health Uniform National
      Data Systems (PHUND$). Shortly thereafter, a group was convened to work with
      public health practitioners and researchers to develop a uniform chart of
      accounts crosswalk. A year-long process was undertaken to create the crosswalk.
      This commentary discusses that process, challenges encountered along the way and
      provides a draft crosswalk in line with the Foundational Public Health Services
      model that, if used by health departments, could allow for meaningful comparisons
      between agencies. 

PMID- 26214537
TI  - Transitioning From "Public Health Has the Data" to "Public Health Has the
      Answers".

PMID- 26214538
TI  - Joint Recommendations for the Public Health Informatics Infrastructure.

PMID- 26214539
TI  - Women's knowledge about heart disease: Differences among ethnic and cultural
      groups in the Israeli Women's Health in Midlife Study.
AB  - The current investigation aimed to assess levels of knowledge about risk factors
      for heart disease among midlife Israeli women, and to evaluate the relationship
      of knowledge to personal risk factors and vulnerability to heart disease. Face-to
      face interviews with women aged 45-64 years were conducted during 2004-2006
      within three population groups: long-term Jewish residents (LTR), immigrants from
      the former Soviet Union, and Arab women. The survey instrument included six
      knowledge statements relating to: the risk after menopause, family history,
      elevated cholesterol level, diabetes, obesity, and warning signs of a heart
      attack. The findings showed wide disparities in knowledge by educational level
      and between immigrants and LTR, after taking into account personal risk factors
      and education. Personal risk factors were not significantly related to the
      knowledge items, except for personal history of cardiovascular disease, which was
      associated with knowledge about "warning signs of a heart attack" and "family
      history." Women who perceived themselves as more vulnerable to heart disease were
      more likely to identify several risk factors correctly. These findings stress the
      need to increase knowledge about heart disease, especially among less educated
      and minority women, and to emphasize the risk of patients' personal status by
      health providers. 

PMID- 26214540
TI  - Changes in posttraumatic cognitions predict changes in posttraumatic stress
      disorder symptoms during cognitive processing therapy.
AB  - OBJECTIVE: Although cognitive processing therapy (CPT) has strong empirical
      support as a treatment for posttraumatic stress disorder (PTSD), studies have not
      directly examined the proposed change mechanisms that underlie CPT-that change in
      trauma-related cognitions produces change in PTSD and depression symptoms. To
      improve the understanding of underlying mechanisms of psychotherapeutic change,
      this study investigated longitudinal association between trauma-related
      cognitions, PTSD, and depression among veterans receiving CPT during a 7-week
      residential PTSD treatment program. METHOD: All 195 veterans met DSM-IV-TR
      diagnosis for PTSD. The sample was 53% male with a mean age of 48 years. Self
      reported race was 50% White and 45% African American. The Posttraumatic
      Cognitions Inventory was used to assess trauma-related cognitions. The PTSD
      Checklist and Beck Depression Inventory-II were used to assess PTSD and
      depression, respectively. Cross-lagged panel models were used to test the
      longitudinal associations between trauma-related cognitions, PTSD, and
      depression. Measures were administered at three time points: pre-, mid-, and
      posttreatment. RESULTS: Change in posttraumatic cognitions (self-blame; negative
      beliefs about the self) preceded change in PTSD. In addition, (a) change in
      negative beliefs about the self preceded change in depression, (b) change in
      depression preceded change in self-blame cognitions, and (c) change in depression
      preceded change in PTSD. CONCLUSION: Findings support the hypothesized underlying
      mechanisms of CPT in showing that change in trauma-related cognitions precedes
      change in PTSD symptoms. Results suggest that reduction of depression may be
      important in influencing reduction of PTSD among veterans in residential PTSD
      treatment.

PMID- 26214541
TI  - Testing gene * environment moderation of tobacco and marijuana use trajectories
      in adolescence and young adulthood.
AB  - OBJECTIVE: This study examines the main and interaction effects of known social
      risk factors for substance use (inadequate parental monitoring and substance
      using friends) in adolescence and a polygenic score in predicting marijuana and
      tobacco use in adolescence and young adulthood. METHOD: Phenotypic and genetic
      data were derived from a longitudinal study of a cohort of urban, predominately
      African American youth. Last year substance-use measures were collected annually
      from 8th grade through age 22. Participant self-reports of substance-using
      friends and parent monitoring were obtained yearly from Grades 8 to 12. Using
      longitudinal latent class analysis, the authors identified parallel developmental
      trajectories of tobacco and marijuana use and parent monitoring and the
      proportion of substance-using friends. RESULTS: Two trajectories were identified
      for tobacco and marijuana use, characterized by moderate versus little-to-no use.
      Additionally, 2 latent profiles were found for the social environment profiles:
      those characterized by higher parent monitoring and a lower proportion of
      substance-using friends versus lower parent monitoring and a higher proportion of
      substance-using friends. CONCLUSIONS: We found main and interaction effects for
      the polygenic score and social environment profile in predicting the longitudinal
      classes of marijuana and tobacco use. With respect to the interaction effect,
      membership in the moderate-use classes of marijuana and tobacco use was highest
      among those in the social environment profile characterized by lower parent
      monitoring and a higher proportion of substance-using friends.

PMID- 26214542
TI  - Identifying moderators of the adherence-outcome relation in cognitive therapy for
      depression.
AB  - OBJECTIVE: Little is known about the influence of patients' pretreatment
      characteristics on the adherence-outcome relation in cognitive therapy (CT) for
      depression. In a sample of 57 depressed adults participating in CT, the authors
      examined interactions between pretreatment patient characteristics and therapist
      adherence in predicting session-to-session symptom change. METHOD: Using items
      from the Collaborative Study Psychotherapy Rating Scale, the authors assessed 3
      facets of therapist adherence: cognitive methods, negotiating/structuring, and
      behavioral methods/homework. Two graduate students rated Sessions 1-4 for
      adherence. Symptoms were assessed prior to each session with the Beck Depression
      Inventory-II. Moderators were assessed as part of patients' intake evaluations.
      RESULTS: After correcting for multiple comparisons, patient gender remained a
      significant moderator of the relationship between cognitive methods and next
      session symptom change; cognitive methods more strongly predicted greater symptom
      improvement for women as compared to men. Pretreatment anxiety and number of
      prior depressive episodes were significant moderators of the relationship between
      behavioral methods/homework and next-session symptom change, with greater
      behavioral methods/homework predicting symptom improvement more strongly among
      patients high in pretreatment anxiety and among patients with relatively few
      prior depressive episodes. CONCLUSIONS: This is the first study to provide
      evidence of how therapist adherence is differentially related to outcome among
      depressed patients with different characteristics. If replicated, these findings
      may inform clinical decisions regarding the use of specific facets of adherence
      in CT for depression with specific patients.

PMID- 26214543
TI  - Children of divorce-coping with divorce: A randomized control trial of an online
      prevention program for youth experiencing parental divorce.
AB  - OBJECTIVE: Evaluate an online coping skills program to prevent mental health
      problems in children and adolescents from divorced or separated families. METHOD:
      Children ages 11-16 (N = 147) whose families had filed for divorce were recruited
      using public court records. Participants were blocked by risk-score and randomly
      assigned to either a control (Internet self-study condition, Best of the Net
      (BTN) or the experimental intervention, Children of Divorce-Coping With Divorce
      (CoD-CoD), a 5-module highly interactive online program to promote effective
      coping skills. Program effects were tested on measures of children's self
      reported coping and parent and youth reports of children's mental health
      problems. RESULTS: Significant main effects indicated that youth in CoD-CoD
      improved more on self-reported emotional problems relative to BTN youth (d = .37)
      and had a lower rate of clinically significant self-reported mental health
      problems (OR = .58, p = .04). A significant Baseline * Treatment interaction
      indicated that the 55% of youth with highest baseline problems improved more than
      those in BTN on their self-report of total mental health problems. A significant
      interaction effect indicated that CoD-CoD improved youth coping efficacy for the
      30% of those with the lowest baseline coping efficacy. For the 10% of youth with
      lowest parent-reported risk at baseline, those who received BTN had lower
      problems than CoD-CoD participants. CONCLUSIONS: CoD-CoD was effective in
      reducing youth-reported mental health problems and coping efficacy particularly
      for high risk youth. Parent-report indicated that, relative to BTN, CoD-CoD had a
      negative effect on mental health problems for a small group with the lowest risk.

PMID- 26214545
TI  - Correction to Grilo et al. (2015).
AB  - Reports an error in "Predicting meaningful outcomes to medication and self-help
      treatments for binge-eating disorder in primary care: The significance of early
      rapid response" by Carlos M. Grilo, Marney A. White, Robin M. Masheb and Ralitza
      Gueorguieva (Journal of Consulting and Clinical Psychology, 2015[Apr], Vol 83[2],
      387-394). The axis labels are missing on Figure 3. A corrected figure appears in
      the correction. (The following abstract of the original article appeared in
      record 2015-02674-001.) OBJECTIVE: We examined rapid response among obese
      patients with binge-eating disorder (BED) in a randomized clinical trial testing
      antiobesity medication and self-help cognitive-behavioral therapy (shCBT), alone
      and in combination, in primary-care settings. METHOD: One hundred four obese
      patients with BED were randomly assigned to 1 of 4 treatments: sibutramine,
      placebo, shCBT + sibutramine, or shCBT + placebo. Treatments were delivered by
      generalist primary-care physicians and the medications were given double-blind.
      Independent assessments were performed by trained and monitored doctoral research
      clinicians monthly throughout treatment, posttreatment (4 months), and at 6- and
      12-month follow-ups (i.e., 16 months after randomization). Rapid response,
      defined as >=65% reduction in binge eating by the fourth treatment week, was used
      to predict outcomes. RESULTS: Rapid response characterized 47% of patients, was
      unrelated to demographic and baseline clinical characteristics, and was
      significantly associated, prospectively, with remission from binge eating at
      posttreatment (51% vs. 9% for nonrapid responders), 6-month (53% vs. 23.6%), and
      12-month (46.9% vs. 23.6%) follow-ups. Mixed-effects model analyses revealed that
      rapid response was significantly associated with greater decreases in binge
      eating or eating-disorder psychopathology, depression, and percent weight loss.
      DISCUSSION: Our findings, based on a diverse obese patient group receiving
      medication and shCBT for BED in primary-care settings, indicate that patients who
      have a rapid response achieve good clinical outcomes through 12-month follow-ups
      after ending treatment. Rapid response represents a strong prognostic indicator
      of clinically meaningful outcomes, even in low-intensity medication and self-help
      interventions. Rapid response has important clinical implications for stepped
      care treatment models for BED. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov:
      NCT00537810

PMID- 26214544
TI  - Effect of patient choice in an adaptive sequential randomization trial of
      treatment for alcohol and cocaine dependence.
AB  - OBJECTIVE: To evaluate the effect of providing choice of treatment alternatives
      to patients who fail to engage in or drop out of intensive outpatient programs
      (IOPs) for substance dependence. METHOD: Alcohol- and/or cocaine-dependent
      patients (N = 500) participated in a sequential, multiple-assignment, randomized
      trial (SMART). Those who failed to engage in an IOP at Week 2 (N = 189) or who
      dropped out after engagement (N = 84) were randomized for motivational
      interviewing (MI) telephone calls that focused on engagement in an IOP (MI-IOP)
      or provided a choice of IOP type or 3 treatment options (MI-PC, or patient
      choice). Those not engaged at both 2 and 8 weeks (N = 102) were re-randomized
      either to MI-PC or no further outreach. Outcomes were treatment attendance and
      measures of alcohol and cocaine use obtained at 1, 2, 3, and 6 months. RESULTS:
      MI-PC produced better attendance than comparison conditions in patients who
      dropped out after initial engagement and in those re-randomized at 8 weeks.
      However, contrary to study hypotheses, MI-IOP produced significantly better
      alcohol-use outcomes than MI-PC in alcohol-dependent patients not engaged at Week
      2. There were no other significant differences between treatment conditions on
      other main-effect analyses with alcohol- or cocaine-outcome measures. CONCLUSION:
      Providing treatment options via telephone calls to patients who failed to engage
      in IOP did not produce better substance-use outcomes than outreach calls focused
      on engagement in IOP. Future researchers should investigate the potential
      benefits of choice at other points in treatment (e.g., at intake) as well as
      choice of other combinations of treatments.

PMID- 26214546
TI  - Hemorheological Approach for Early Detection of Chronic Kidney Disease and
      Diabetic Nephropathy in Type 2 Diabetes.
AB  - BACKGROUND: Hemorheologic alterations or changes in blood viscosity have been
      suggested to play a role in the pathogenesis of microvascular complications in
      diabetes. We measured various hemorheologic parameters in type 2 diabetes
      patients at different stages of chronic kidney disease (CKD) and assessed their
      possible role as early markers of diabetic nephropathy and renal insufficiency.
      SUBJECTS AND METHODS: One hundred-five patients with type 2 diabetes were divided
      into four groups according to glomerular filtration rate (GFR), which represents
      the kidney function. Hemorheologic parameters, including erythrocyte
      deformability, fibrinogen/elongation index (EI), and aggregation index (AI) were
      measured using a microfluidic hemorheometer, and critical shear stress (CSS) was
      measured using a microfluidic technique. Various metabolic parameters were
      assessed from fasting blood samples, and the urine albumin-to-creatinine ratio
      (ACR) was calculated from first morning voided urine. RESULTS: There were
      significant differences in red blood cell (RBC) deformability, AI, CSS,
      fibrinogen/EI, and ACR among patients in different stages of CKD (all P<0.05).
      RBC deformability and fibrinogen/EI significantly differed between normal (GFR
      >90 mL/min/1.73 m(2)) and CKD stage 2 (GFR 60-90 mL/min/1.73 m(2)) patients,
      whereas there was no such difference in ACR. In multiple regression analysis,
      fibrinogen/EI under a moderate shear stress of 3 Pa was an independent predictor
      of GFR (beta=-0.328, P<0.05). Also, AI, CSS, and fibrinogen/EI were significantly
      different among patients at different stages of diabetic nephropathy, with a
      significant difference in fibrinogen/EI between normal and microalbuminuric
      patients (all P<0.05). CONCLUSIONS: RBC deformability and fibrinogen/EI are
      sensitive parameters measured via point-of-care testing for detecting erythrocyte
      alterations in early CKD and nephropathy in patients with type 2 diabetes.
      Further studies are warranted to verify their use as screening tools for diabetic
      nephropathy and renal impairment.

PMID- 26214547
TI  - The Influence of Weight-of-Evidence Messages on (Vaccine) Attitudes: A Sequential
      Mediation Model.
AB  - Media coverage of contentious risk issues often features competing claims about
      whether a risk exists and what scientific evidence shows, and journalists often
      cover these issues by presenting both sides. However, for topics defined by
      scientific agreement, balanced coverage erroneously heightens uncertainty about
      scientific information and the issue itself. In this article, we extend research
      on combating so-called information and issue uncertainty using weight of
      evidence, drawing on the discredited autism-vaccine link as a case study. We
      examine whether people's perceptions of issue uncertainty (about whether a link
      exists) change before and after they encounter a news message with weight-of
      evidence information. We also explore whether message exposure is associated with
      broader issue judgments, specifically vaccine attitudes. Participants (n = 181)
      read news articles that included or omitted weight-of-evidence content stating
      that scientific studies have found no link and that scientists agree that none
      exists. Postexposure issue uncertainty decreased-in other words, issue certainty
      increased-from preexposure levels across all conditions. Moreover, weight-of
      evidence messages were associated with positive vaccine attitudes indirectly via
      reduced information uncertainty (i.e., one's belief that scientific opinion and
      evidence concerning a potential link is unclear) as well as issue uncertainty. We
      discuss implications for risk communication. 

PMID- 26214549
TI  - Thermochemistry of Multiferroic Organic-Inorganic Hybrid Perovskites
      [(CH3)2NH2][M(HCOO)3] (M = Mn, Co, Ni, and Zn).
AB  - Organic-inorganic hybrid materials have enormous potential for applications in
      catalysis, gas storage, sensors, drug delivery, and energy generation, among
      others. A class of hybrid materials adopts the ABX3 perovskite topology. We
      report here the synthesis and characterization of an isostructural series of
      dense hybrid perovskites, [(CH3)2NH2][M(HCOO)3], with M = Mn, Co, Ni, and Zn.
      These compounds have shown promising multiferroic behavior. Understanding their
      stability is crucial for their practical application. We report their formation
      enthalpies based on direct measurement by room-temperature acid solution
      calorimetry. The enthalpy of formation of this dimethylammonium metal formate
      series becomes less exothermic in the order Mn, Zn, Co, Ni. The stability of the
      hybrid perovskite decreases as the tolerance factor increases, unlike trends seen
      in inorganic perovskites. However, the trends are similar to those seen in a
      number of ternary transition metal oxides, suggesting that specific bonding
      interactions rather than geometric factors dominate the energetics. 

PMID- 26214548
TI  - HIV Transmission Patterns Among Immigrant Latinos Illuminated by the Integration
      of Phylogenetic and Migration Data.
AB  - Latinos represent a growing proportion of HIV cases in North Carolina (NC).
      Understanding how immigrants are involved in local HIV transmission is important
      to guide interventions. We used phylogenetics to characterize Latino involvement
      in local HIV transmission chains. Transmission clusters were identified from
      maximum-likelihood phylogenies constructed with HIV pol sequences from 177
      Latinos and 1,496 non-Latinos receiving care in NC. Highly supported clusters
      involving one or more Latinos were characterized. Migration data were obtained
      from interviews and chart review. Factors associated with cluster membership were
      identified using log-binomial regression. Most Latinos were male (76%),
      immigrants (83%), and had HIV-1B (99%). Immigrants were more likely to report
      heterosexual risk (67% vs. 23%) than U.S.-born Latinos (p < 0.01). We identified
      32 clusters that included one or more Latinos; these involved 53 Latinos (30%)
      and 41 non-Latinos. Immigrant and U.S.-born Latinos were equally likely to be in
      clusters, but immigrants were more likely to be in clusters with another Latino
      (78% vs. 29%; p = 0.02). Cluster composition by ethnicity and risk behavior
      varied by cluster size; larger clusters contained fewer immigrants and more men
      who have sex with men (MSM). Factors associated with immigrant membership in
      local transmission clusters included age <30 years [RR 2.34 (95% CI 1.47-3.73)],
      Mexican origin [RR 2.55 (95% CI 1.29-6.88)], and residing in the United States
      longer before diagnosis [RR 1.53 (95% CI 1.09-2.15), per 10 years]. While some
      Latinos immigrate with HIV infection, many immigrants are involved in
      transmission networks after arrival, particularly MSM. HIV testing and prevention
      interventions must consider this heterogeneity and may be better targeted by
      integrating phylogenetic analyses. 

PMID- 26214550
TI  - A New Approach to Pathogen Containment in the Operating Room: Sheathing the
      Laryngoscope After Intubation.
AB  - BACKGROUND: Anesthesiologists may contribute to postoperative infections by means
      of the transmission of blood and pathogens to the patient and the environment in
      the operating room (OR). Our primary aims were to determine whether contamination
      of the IV hub, the anesthesia work area, and the patient could be reduced after
      induction of anesthesia by removing the risk associated with contaminants on the
      laryngoscope handle and blade. Therefore, we conducted a study in a simulated OR
      where some of the participants sheathed the laryngoscope handle and blade in a
      glove immediately after it was used to perform an endotracheal intubation.
      METHODS: Forty-five anesthesiology residents (postgraduate year 2-4) were
      enrolled in a study consisting of identical simulation sessions. On entry to the
      simulated OR, the residents were asked to perform an anesthetic, including
      induction and endotracheal intubation timed to approximately 6 minutes. Of the 45
      simulation sessions, 15 were with a control group conducted with the intubating
      resident wearing single gloves, 15 with the intubating resident using double
      gloves with the outer pair removed and discarded after verified intubation, and
      15 wearing double gloves and sheathing the laryngoscope in one of the outer
      gloves after intubation. Before the start of the scenario, the lips and inside of
      the mouth of the mannequin were coated with a fluorescent marking gel. After each
      of the 45 simulations, an observer examined the OR using an ultraviolet light to
      determine the presence of fluorescence on 25 sites: 7 on the patient and 18 in
      the anesthesia environment. RESULTS: Of the 7 sites on the patient, ultraviolet
      light detected contamination on an average of 5.7 (95% confidence interval, 4.4
      7.2) sites under the single-glove condition, 2.1 (1.5-3.1) sites with double
      gloves, and 0.4 (0.2-1.0) sites with double gloves with sheathing. All 3
      conditions were significantly different from one another at P < 0.001. Of the 18
      environmental sites, ultraviolet light detected fluorescence on an average of
      13.2 (95% confidence interval, 11.3-15.6) sites under the single-glove condition,
      3.5 (2.6-4.7) with double gloves, and 0.5 (0.2-1.0) with double gloves with
      sheathing. Again, all 3 conditions were significantly different from one another
      at P < 0.001. CONCLUSIONS: The results of this study suggest that when an
      anesthesiologist in a simulated OR sheaths the laryngoscope immediately after
      endotracheal intubation, contamination of the IV hub, patient, and intraoperative
      environment is significantly reduced.

PMID- 26214551
TI  - The Analgesic Effect of Rolipram, a Phosphodiesterase 4 Inhibitor, on
      Chemotherapy-Induced Neuropathic Pain in Rats.
AB  - BACKGROUND: Chemotherapy-induced neuropathic pain is a significant side effect of
      chemotherapeutic agents. Currently, there are no effective analgesics for
      chemotherapy-induced neuropathic pain. Rolipram is a selective phosphodiesterase
      4 inhibitor, which increases intracellular cyclic AMP in nerve and immune cells.
      The aim of our study was to determine the analgesic effects of rolipram on
      paclitaxel (PAC)-induced neuropathic pain in rats. METHODS: Chemotherapy-induced
      neuropathic pain was produced by intraperitoneal injection of PAC on 4 alternate
      days in male Sprague-Dawley rats. Mechanical allodynia was measured by using von
      Frey filaments. RESULTS: After the rats developed PAC-induced pain behavior (such
      as mechanical allodynia), a single intraperitoneal injection and continuous
      infusion of rolipram ameliorated PAC-induced pain behavior. In addition, systemic
      infusion of the drug during the early phase of developing pain behavior did not
      prevent the development of mechanical allodynia induced by PAC. CONCLUSIONS:
      These results suggest that rolipram alleviated mechanical allodynia induced by
      PAC in rats. Thus, phosphodiesterase 4 inhibitors may prove useful in the
      treatment of chemotherapy-induced neuropathic pain. However, further studies are
      needed to clarify their effects in clinical settings.

PMID- 26214553
TI  - Evidence that Additions of Grignard Reagents to Aliphatic Aldehydes Do Not
      Involve Single-Electron-Transfer Processes.
AB  - Addition of allylmagnesium reagents to an aliphatic aldehyde bearing a radical
      clock gave only addition products and no evidence of ring-opened products that
      would suggest single-electron-transfer reactions. The analogous Barbier reaction
      also did not provide evidence for a single-electron-transfer mechanism in the
      addition step. Other Grignard reagents (methyl-, vinyl-, t-Bu-, and
      triphenylmethylmagnesium halides) also do not appear to add to an alkyl aldehyde
      by a single-electron-transfer mechanism. 

PMID- 26214552
TI  - Balancing Model Performance and Simplicity to Predict Postoperative Primary Care
      Blood Pressure Elevation.
AB  - BACKGROUND: Because of uncertainty regarding the reliability of perioperative
      blood pressures and traditional notions downplaying the role of anesthesiologists
      in longitudinal patient care, there is no consensus for anesthesiologists to
      recommend postoperative primary care blood pressure follow-up for patients
      presenting for surgery with an increased blood pressure. The decision of whom to
      refer should ideally be based on a predictive model that balances performance
      with ease-of-use. If an acceptable decision rule was developed, a new practice
      paradigm integrating the surgical encounter into broader public health efforts
      could be tested, with the goal of reducing long-term morbidity from hypertension
      among surgical patients. METHODS: Using national data from US veterans receiving
      surgical care, we determined the prevalence of poorly controlled outpatient
      clinic blood pressures >=140/90 mm Hg, based on the mean of up to 4 readings in
      the year after surgery. Four increasingly complex logistic regression models were
      assessed to predict this outcome. The first included the mean of 2 preoperative
      blood pressure readings; other models progressively added a broad array of
      demographic and clinical data. After internal validation, the C-statistics and
      the Net Reclassification Index between the simplest and most complex models were
      assessed. The performance characteristics of several simple blood pressure
      referral thresholds were then calculated. RESULTS: Among 215,621 patients, poorly
      controlled outpatient clinic blood pressure was present postoperatively in 25.7%
      (95% confidence interval [CI], 25.5%-25.9%) including 14.2% (95% CI, 13.9%-14.6%)
      of patients lacking a hypertension history. The most complex prediction model
      demonstrated statistically significant, but clinically marginal, improvement in
      discrimination over a model based on preoperative blood pressure alone (C
      statistic, 0.736 [95% CI, 0.734-0.739] vs 0.721 [95% CI, 0.718-0.723]; P for
      difference <0.0001). The Net Reclassification Index was 0.088 (95% CI, 0.082
      0.093); P < 0.0001. A preoperative blood pressure threshold >=150/95 mm Hg,
      calculated as the mean of 2 readings, identified patients more likely than not to
      demonstrate outpatient clinic blood pressures in the hypertensive range. Four of
      5 patients not meeting this criterion were indeed found to be normotensive during
      outpatient clinic follow-up (positive predictive value, 51.5%; 95% CI, 51.0-52.0;
      negative predictive value, 79.6%; 95% CI, 79.4-79.7). CONCLUSIONS: In a national
      cohort of surgical patients, poorly controlled postoperative clinic blood
      pressure was present in >1 of 4 patients (95% CI, 25.5%-25.9%). Predictive
      modeling based on the mean of 2 preoperative blood pressure measurements
      performed nearly as well as more complicated models and may provide acceptable
      predictive performance to guide postoperative referral decisions. Future studies
      of the feasibility and efficacy of such referrals are needed to assess possible
      beneficial effects on long-term cardiovascular morbidity.

PMID- 26214554
TI  - Characterization of Resistances of a Capacitive Deionization System.
AB  - Capacitive deionization (CDI) is a promising desalination technology, which
      operates at low pressure, low temperature, requires little infrastructure, and
      has the potential to consume less energy for brackish water desalination.
      However, CDI devices consume significantly more energy than the theoretical
      thermodynamic minimum, and this is at least partly due to resistive power
      dissipation. We here report our efforts to characterize electric resistances in a
      CDI system, with a focus on the resistance associated with the contact between
      current collectors and porous electrodes. We present an equivalent circuit model
      to describe resistive components in a CDI cell. We propose measurable figures of
      merit to characterize cell resistance. We also show that contact pressure between
      porous electrodes and current collectors can significantly reduce contact
      resistance. Lastly, we propose and test an alternative electrical contact
      configuration which uses a pore-filling conductive adhesive (silver epoxy) and
      achieves significant reductions in contact resistance.

PMID- 26214555
TI  - Low-Dose Fluvastatin and Valsartan Rejuvenate the Arterial Wall Through
      Telomerase Activity Increase in Middle-Aged Men.
AB  - BACKGROUND AND AIM: Previously, we have shown that slightly to moderately aged
      arteries in middle-aged males can be rejuvenated functionally by sub-therapeutic,
      low-dose fluvastatin and valsartan treatment. Here, we explore whether this
      treatment could also increase telomerase activity. We hypothesized that
      telomerase activity might be associated with (1) an improvement of arterial wall
      properties and (2) a reduction of inflammatory/oxidative stress parameters (both
      observed in our previous studies). METHODS: The stored blood samples from 130
      apparently healthy middle-aged males treated with fluvastatin (10 mg daily),
      valsartan (20 mg daily), fluvastatin and valsartan combination (10 and 20 mg),
      respectively, and placebo (control), were analyzed. The samples were taken before
      and after treatment lasting 30 days, and 5 months after treatment
      discontinuation. Telomerase activity was measured in blood leukocytes by a TaqMan
      Gene Expression Assay. RESULTS: Low-dose fluvastatin or valsartan increased
      telomerase activity (106.9% and 59.5% respectively; both p < 0.05, vs. control),
      whereas their combination was even more effective (an increase of 228.0%; p <
      0.001, vs. control). No change was noted in the control group. Importantly,
      increased telomerase activity obtained in the combination group significantly
      correlated with arterial function, measured by flow-mediated dilation (FMD) (r =
      0.79; p < 0.001) and C-reactive protein concentration (r = -0.54; p = 0.02) and
      total anti-oxidative status (r = 0.50; p = 0.03). CONCLUSION: We found that a low
      dose combination of fluvastatin and valsartan substantially increased telomerase
      activity, which significantly correlated with an improvement of endothelial
      function and a decrease of inflammation/oxidative stress. These findings could
      lead to a new innovative approach to arterial rejuvenation.

PMID- 26214556
TI  - Mental/Behavioral Health Services: Medicaid Home and Community-Based Services
      1915(c) Waiver Allocation for People With Intellectual and Developmental
      Disabilities.
AB  - Research has indicated that people who have intellectual and developmental
      disabilities (IDD) appear to be more vulnerable to having a co-existing
      psychiatric diagnosis. This study examined Medicaid 1915(c) Home and Community
      Based Services (HCBS) waiver applications for people with IDD to determine the
      mental/behavioral health services proposed. We found that a large variance exists
      across states in projected spending for services, spending per participant,
      annual hours of service per participant, and hourly reimbursement rates.
      Moreover, compared to overall funding we found a general lack of state commitment
      to mental/behavioral services. States must shore up the capacity of their HCBS
      1915 

PMID- 26214557
TI  - Adapting Phonological Awareness Interventions for Children With Down Syndrome
      Based on the Behavioral Phenotype: A Promising Approach?
AB  - Many children with Down syndrome demonstrate deficits in phonological awareness,
      a prerequisite to learning to read in an alphabetic language. The purpose of this
      study was to determine whether adapting a commercially available phonological
      awareness program to better align with characteristics associated with the
      behavioral phenotype of Down syndrome would increase children's learning of
      phonological awareness, letter sounds, and words. Five children with Down
      syndrome, ages 6 to 8 years, participated in a multiple baseline across
      participants single case design experiment in which response to an adapted
      phonological awareness intervention was compared with response to the nonadapted
      program. Results indicate a functional relation between the adapted program and
      phonological awareness. Suggestions for future research and implications for
      practice are provided. 

PMID- 26214558
TI  - Psychotropic and Anticonvulsant Medication: Individuals With Intellectual and
      Developmental Disabilities Who Transitioned to the Community From an Institution.
AB  - Influenced by Georgia's settlement agreement with the United States Department of
      Justice relating to the enforcement of the Americans with Disabilities Act, an
      increasing number of individuals with intellectual and developmental disabilities
      (IDD) are transitioning from institutions to community living. In this study we
      evaluate the pattern of medication use among individuals who recently
      transitioned to the community (IRTC), comparing results to the IDD population
      already residing in the community (comparison group). Average use and prevalence
      rates were trended over time, between January 1, 2010, and December 31. 2012.
      Findings indicate a significant increase in medication use in the IRTC and
      comparison group, with a greater and faster increase in the IRTC population. We
      suggest the transition process should be examined and revised, ensuring adequate
      preparation time and training for each person and relevant staff, particularly on
      medications and challenging behaviors. Several demographic trends were also
      significant and are discussed. 

PMID- 26214559
TI  - Validating the Learning Disability Screening Questionnaire Against the Weschler
      Adult Intelligence Scale, Fourth Edition.
AB  - The Learning Disability Screening Questionnaire (LDSQ), a brief screening tool
      for intellectual disability, was originally validated against the Weschler Adult
      Intelligence Scale, Third Edition (WAIS-III), which was superseded by the
      Weschler Adult Intelligence Scale, Fourth Edition (WAIS-IV) in the United Kingdom
      in 2010. This study examines the performance of the LDSQ using the WAIS-IV as the
      diagnostic intellectual assessment. Based on the original optimal cut-off score,
      the LDSQ sensitivity value was equivalent (91%) to that obtained in the original
      validation study, and the specificity value was higher at 92%. This suggests that
      the LDSQ remains valid when using the WAIS-IV as the comparative intellectual
      assessment. 

PMID- 26214560
TI  - The Negative Effects of Public Benefits on Individual Employment: A Multilevel
      Analysis of Work Hours.
AB  - Public benefits are widely used by people with intellectual and development
      disabilities (IDD) as crucial financial supports. Using Rehabilitation Service
      Administration 911 and Annual Review Report datasets to account for individual
      and state vocational rehabilitation (VR) agency variables, a sample of 21,869
      people with IDD were analyzed using hierarchical linear modeling to model the
      effects of public benefits on hours worked per week. Findings point to
      associations that indicate that public benefits not only limit access to
      employment participation, they also have a restricting effect on growth of weekly
      hours that typically come with higher wage positions, compared those that do not
      access benefits. The article also lays out important implications and
      recommendations to increase the inclusion of people with IDD in the workplace. 

PMID- 26214563
TI  - Multiband superconductivity in Ta4Pd3Te16 with anisotropic gap structure.
AB  - We carried out measurements of the magnetoresistance, magnetic susceptibility and
      specific heat on crystals of the low-dimensional transition metal telluride
      Ta4Pd3Te16. Our results indicate that Ta4Pd3Te16 is an anisotropic type-II
      superconductor in the clean limit with the extracted Ginzburg-Landau parameter
      KGL = 84. The upper critical field Hc2(T) shows an anomalous temperature
      dependence at low temperatures and the anisotropy of Hc2(T) is strongly T
      dependent, both of which indicate a multiband scenario. The electronic specific
      heat Cel(T) can be consistently described by a two-gap (s   +   d waves) model
      from the base temperature T/Tc ~ 0.12 up to Tc. Our results suggest nodal and
      multiband superconductivity in Ta4Pd3Te16.

PMID- 26214564
TI  - Clinical Use of Loop Gain Measures to Determine Continuous Positive Airway
      Pressure Efficacy in Patients with Complex Sleep Apnea. A Pilot Study.
AB  - RATIONALE: Measures of unstable ventilatory control (loop gain) can be obtained
      directly from the periodic breathing duty ratio on polysomnography in patients
      with Cheyne-Stokes respiration/central sleep apnea and can predict the efficacy
      of continuous positive airway pressure (CPAP) therapy. OBJECTIVES: In this pilot
      study, we aimed to determine if this measure could also be applied to patients
      with complex sleep apnea (predominant obstructive sleep apnea, with worsening or
      emergent central apneas on CPAP). We hypothesized that loop gain was higher in
      patients whose central events persisted 1 month later despite CPAP treatment
      versus those whose events resolved over time. METHODS: We calculated the duty
      ratio of the periodic central apneas remaining on the CPAP titration (or second
      half of the split night) while patients were on optimal CPAP with the airway open
      (obstructive apnea index < 1/h). Loop gain was calculated by the formula: LG =
      2pi/[(2piDR - sin(2piDR)]. Patients were followed on CPAP for 1 month. Post
      treatment apnea-hypopnea index and compliance data were recorded from smart
      cards. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients with complex sleep
      apnea were identified, and 17 patients had full data sets. Eight patients
      continued to have a total of more than five events per hour (11.8 +/- 0.5/h)
      (nonresponders). The remaining nine patients had an apnea-hypopnea index less
      than 5/h (2.2 +/- 0.4/h) (responders). Loop gain was higher in the nonresponders
      versus responders (2.0 +/- 0.1 vs. 1.7 +/- 0.2, P = 0.026). Loop gain and the
      residual apnea-hypopnea index 1 month after CPAP were associated (r = 0.48, P =
      0.02). CPAP compliance was similar between groups. CONCLUSIONS: In this pilot
      study, loop gain was higher for patients with complex sleep apnea in whom central
      apneas persisted after 1 month of CPAP therapy (nonresponders). Loop gain
      measurement may enable an a priori determination of those who need alternative
      modes of positive airway pressure.

PMID- 26214566
TI  - Comparison of blood transfusion and surgical complications in peripartum
      hysterectomy when anticipated and unanticipated.
AB  - The aim of the study was to determine the incidence and aetiology of peripartum
      hysterectomy (PH) for major obstetric haemorrhage (MOH) in our population and to
      compare estimated blood loss (EBL), blood transfusion, surgical complications and
      duration of hospital stay in PH that was anticipated and PH that was
      unanticipated. 26 cases of MOH requiring PH were identified from 50,548 women who
      delivered between 1 January 2006 and 31 December 2011 (0.5/1000). PH was
      anticipated in 17 and unanticipated in 9 cases. When compared, the anticipated
      group was more likely to have placenta accreta 15/17 (88%) vs 4/9 (44%): p = 0.03
      and a gynaecological oncologist as the principal operator 15/17 (88%) vs 3/9
      (33%): p = 0.007. The EBL 5.5 +/- 3.7 SD vs 6.6 +/- 3.9 SD l; p = 0.5, units of
      red cell concentrate or RCC transfused 7 +/- 5 SD vs 9 +/- 5 SD: p = 0.3, and
      mean operating time 134 +/- 60 SD vs 190 +/- 96 SD min: p = 0.07 were less in the
      anticipated than the unanticipated group, but not significantly so. The
      intraoperative complication rate 7/17 (41%) vs 3/9 (33%): p = 1.0 and the mean
      duration of hospital stay 7 +/- 1 SD vs 8 +/- 3 SD days: p = 0.27 were similar in
      both groups. PH is associated with a large volume of blood loss and significant
      surgical complications regardless of whether the procedure is anticipated or not.

PMID- 26214567
TI  - Is envy categorical or dimensional? An empirical investigation using taxometric
      analysis.
AB  - Researchers frequently disagree about the latent structure of emotions.
      Taxometric analysis--a method for determining whether the latent structure of a
      construct is best defined as categorical or purely dimensional--can be a useful
      tool for resolving these debates. The present study used taxometric analysis to
      investigate the latent structure of envy. Scholars disagree about whether envy is
      necessarily malicious or whether it can also be benign. Van de Ven, Zeelenberg,
      and Pieters (2009) claim that benign envy exists, and that it is distinct from
      malicious envy. Much of their evidence for this claim relies on latent class
      analysis, which can be biased toward creating categories with data that actually
      vary dimensionally (Cleland, Rothschild, & Haslam, 2000; Uebersax, 1999).
      Therefore, taxometric analysis provides a more conservative test for an
      underlying categorical structure. A daily diary procedure was used to measure
      participants' day-to-day experiences of envy. The results support van de Ven et
      al.'s claim that benign envy exists, and that is distinct from malicious envy.

PMID- 26214569
TI  - Limited time perspective increases the value of calm.
AB  - Previous findings indirectly suggest that the more people perceive their time in
      life as limited, the more they value calm. No study, however, has directly tested
      this hypothesis. To this end, using a combination of survey, experience sampling,
      and experimental methods, we examined the relationship between future time
      perspective and the affective states that people ideally want to feel (i.e.,
      their "ideal affect"). In Study 1, the more people reported a limited time
      perspective, the more they wanted to feel calm and experience other low-arousal
      positive states. In Study 2, participants were randomly assigned to a limited
      time or an expanded time condition. Participants in the limited time condition
      reported valuing calm and other low arousal positive states more than those in
      the expanded time condition. We discuss the implications of these findings for
      broadening our understanding of the factors that shape how people ideally want to
      feel, and their consequences for decision making.

PMID- 26214568
TI  - Observed emotion frequency versus intensity as predictors of socioemotional
      maladjustment.
AB  - The purpose of this study was to assess whether observed emotional frequency (the
      proportion of instances an emotion was observed) and intensity (the strength of
      an emotion when it was observed) uniquely predicted kindergartners' (N = 301)
      internalizing and externalizing problems. Analyses were tested in a structural
      equation modeling (SEM) framework with data from multireporters (reports of
      problem behaviors from teachers and parents) and naturalistic observations of
      emotion in the fall semester. For observed positive emotion, both frequency and
      intensity negatively predicted parent- or teacher-reported internalizing
      symptoms. Anger frequency positively predicted parent- and teacher-reported
      externalizing symptoms, whereas anger intensity positively predicted parent- and
      teacher-reported externalizing and parent-reported internalizing symptoms. The
      findings support the importance of examining both aspects of emotion when
      predicting maladjustment.

PMID- 26214570
TI  - Stuck in a sad place: Biased attentional disengagement in rumination.
AB  - Previous research has demonstrated that heightened ruminative disposition is
      characterized by an attentional bias to depressogenic information at 1,000-ms
      exposure durations. However, it is unknown whether this attentional bias reflects
      facilitated attentional engagement with depressogenic information, or impaired
      attentional disengagement from such information. The present study was designed
      to address this question. In keeping with recent theoretical proposals, our
      findings demonstrate that heightened ruminative disposition is associated only
      with impaired attentional disengagement from depressogenic information, and does
      not involve facilitated attentional engagement with such information. In addition
      to resolving this key issue, the present study provided converging support for
      the previous claim that rumination-linked attentional bias is specific to
      depressogenic information, and also lends weight to the contention that
      rumination-linked attentional bias may be evident only when controlled
      attentional processing is readily permitted by using stimulus exposure durations
      of 1,000 ms. We discuss the theoretical implications of these findings and
      highlight key issues for future research.

PMID- 26214571
TI  - Enhanced visual detection in trait anxiety.
AB  - There is much evidence suggesting that trait anxiety is associated with
      impairments in the cognitive control of attention. Recent findings, though, have
      suggested that anxiety may also influence perception, conversely enhancing early
      information processing. The present study investigated this claim within a visual
      detection task. Participants searched for a target letter among a number of
      nontarget letters, varied to modulate the demands or load on perception, while
      also reporting whether an additional stimulus appeared on trials. Self-reported
      trait anxiety levels did not affect performance in the letter search task under
      any level of load. However, visual detection for the additional stimulus, as
      measured by d' sensitivity, was positively correlated with levels of anxiety
      regardless of the perceptual difficulty of the search task. These results suggest
      that trait vulnerability to anxiety is associated with improved visual detection,
      providing direct evidence that anxiety may modulate sensory processing.

PMID- 26214572
TI  - On improving the credibility of candidate gene studies: A review of candidate
      gene studies published in Emotion.
AB  - The discovery of genetic variants associated with psychological traits deepens
      our knowledge about causes and consequences of individual differences. In
      psychology, the standard approach to identify these variants is the "candidate
      gene study." In a candidate gene study, a limited set of genetic variants is
      selected based on their hypothesized or known biological function, and these
      variants are tested for association with the psychological trait of interest. The
      successful replication of published candidate gene studies, however, is
      alarmingly scarce. In this article we describe the challenges to successfully
      identifying genetic associations, and review the candidate gene studies published
      in Emotion. We conclude that the implementation of 4 methodological guidelines
      developed by the Behavior Genetics Association for evaluating candidate gene
      studies will help to increase the credibility of candidate gene study findings.

PMID- 26214573
TI  - The Association between Anhedonia, Suicidal Ideation, and Suicide Attempts in a
      Large Student Sample.
AB  - Depression is a significant risk factor for suicide. Evidence suggests that
      anhedonia may be a symptom of depression that is uniquely associated with
      suicidality. However, exactly how anhedonia is related to suicide is unclear. To
      provide more specific evidence regarding this association, we investigated
      relationships between anhedonia, suicidal ideation, and suicide attempts. A large
      combined undergraduate sample completed the novel Specific Loss of Interest and
      Pleasure Scale (SLIPS), the Center of Epidemiological Studies Depression Scale
      (CES-D), and the Suicidal Behaviors Questionnaire-Revised (SBQ-R). Anhedonia was
      associated with suicidal ideation, even when accounting for depressive symptoms.
      Additionally, anhedonia was not associated with suicide attempts when symptoms of
      depression were held constant. The current study provides novel evidence
      regarding the relationship between anhedonia and risk of attempting suicide.
      Future research can examine the role anhedonia plays in the unfolding of suicidal
      behavior over time. 

PMID- 26214574
TI  - Actigraphically assessed activity in unipolar depression: a comparison of
      inpatients with and without motor retardation.
AB  - OBJECTIVE: To compare the activity patterns of inpatients with unipolar
      depression, who had been divided into groups with and without motor retardation
      prior to actigraphy monitoring. METHOD: Twenty-four-hour actigraphy recordings
      from 52 consecutively, acutely admitted inpatients with unipolar depression (ICD
      10) were compared to recordings from 28 healthy controls. The patients, admitted
      between September 2011 and April 2012, were separated into 2 groups: 25 with
      motor retardation and 27 without motor retardation. Twenty-eight healthy controls
      were also included. Twenty-four-hour recordings, 9-hour daytime sequences, and 64
      minute periods of continuous motor activity in the morning and evening were
      analyzed for mean activity, variability, and complexity. RESULTS: Patients with
      motor retardation had a reduced mean activity level (P = .04) and higher
      intraindividual variability, as shown by increased standard deviation (SD) (P =
      .003) and root mean square successive difference (RMSSD) (P = .025), during 24
      hours compared to the patients without motor retardation. Both patient groups
      demonstrated significantly lower mean activity compared to healthy controls (P <
      .001) as well as higher SD (P < .02) and RMSSD (P < .001) and a higher RMSSD/SD
      ratio (P = .04). In the active morning period, the patients without motor
      retardation displayed significantly increased complexity compared to motor
      retarded patients (P = .006). CONCLUSIONS: The patients with and without motor
      retardation differ in activity patterns. Findings in depressed inpatients without
      motor retardation closely resemble those of inpatients with mania.

PMID- 26214575
TI  - Spontaneous Hot-Electron Light Emission from Electron-Fed Optical Antennas.
AB  - Nanoscale electronics and photonics are among the most promising research areas
      providing functional nanocomponents for data transfer and signal processing. By
      adopting metal-based optical antennas as a disruptive technological vehicle, we
      demonstrate that these two device-generating technologies can be interfaced to
      create an electronically driven self-emitting unit. This nanoscale plasmonic
      transmitter operates by injecting electrons in a contacted tunneling antenna
      feedgap. Under certain operating conditions, we show that the antenna enters a
      highly nonlinear regime in which the energy of the emitted photons exceeds the
      quantum limit imposed by the applied bias. We propose a model based upon the
      spontaneous emission of hot electrons that correctly reproduces the experimental
      findings. The electron-fed optical antennas described here are critical devices
      for interfacing electrons and photons, enabling thus the development of optical
      transceivers for on-chip wireless broadcasting of information at the nanoscale. 

PMID- 26214576
TI  - Introduction of Peripheral Carboxylates to Decrease the Charge on Tm(3+) DOTAM
      Alkyl Complexes: Implications for Detection Sensitivity and in Vivo Toxicity of
      PARACEST MRI Contrast Agents.
AB  - A series of structurally modified Tm(3+) DOTAM-alkyl complexes as potential
      PARACEST MRI contrast agents has been synthesized with the aim to decrease the
      overall positive charge associated with these molecules and increase their
      biocompatibility. Two types of structural modification have been performed, an
      introduction of terminal carboxylate arms to the alkyl side chains and a
      conjugation of one of the alkyl side chains with aspartic acid. Detailed
      evaluation of the magnetic resonance imaging chemical exchange contrast
      associated with the structurally modified contrast agents has been performed. In
      contrast to the acutely toxic Tm(3+) DOTAM-alkyl complexes, the structurally
      modified compounds were found to be tolerated well during in vivo MRI studies in
      mice; however, only the aspartic acid modified chelates produced an amide proton
      based PARACEST signal. 

PMID- 26214577
TI  - Lack of Aggregation of Molecules on Ice Nanoparticles.
AB  - Multiple molecules adsorbed on the surface of nanosized ice particles can either
      remain isolated or form aggregates, depending on their mobility. Such
      (non)aggregation may subsequently drive the outcome of chemical reactions that
      play an important role in atmospheric chemistry or astrochemistry. We present a
      molecular beam experiment in which the controlled number of guest molecules is
      deposited on the water and argon nanoparticles in a pickup chamber and their
      aggregation is studied mass spectrometrically. The studied molecules (HCl, CH3Cl,
      CH3CH2CH2Cl, C6H5Cl, CH4, and C6H6) form large aggregates on argon nanoparticles.
      On the other hand, no aggregation is observed on ice nanoparticles. Molecular
      simulations confirm the experimental results; they reveal a high degree of
      aggregation on the argon nanoparticles and show that the molecules remain mostly
      isolated on the water ice surface. This finding will influence the efficiency of
      ice grain-mediated synthesis (e.g., in outer space) and is also important for the
      cluster science community because it shows some limitations of pickup experiments
      on water clusters.

PMID- 26214578
TI  - Combined transcriptome studies identify AFF3 as a mediator of the oncogenic
      effects of beta-catenin in adrenocortical carcinoma.
AB  - Adrenocortical cancer (ACC) is a very aggressive tumor, and genomics studies
      demonstrate that the most frequent alterations of driver genes in these cancers
      activate the Wnt/beta-catenin signaling pathway. However, the adrenal-specific
      targets of oncogenic beta-catenin-mediating tumorigenesis have not being
      established. A combined transcriptomic analysis from two series of human tumors
      and the human ACC cell line H295R harboring a spontaneous beta-catenin activating
      mutation was done to identify the Wnt/beta-catenin targets. Seven genes were
      consistently identified in the three studies. Among these genes, we found that
      AFF3 mediates the oncogenic effects of beta-catenin in ACC. The Wnt response
      element site located at nucleotide position -1408 of the AFF3 transcriptional
      start sites (TSS) mediates the regulation by the Wnt/beta-catenin signaling
      pathway. AFF3 silencing decreases cell proliferation and increases apoptosis in
      the ACC cell line H295R. AFF3 is located in nuclear speckles, which play an
      important role in RNA splicing. AFF3 overexpression in adrenocortical cells
      interferes with the organization and/or biogenesis of these nuclear speckles and
      alters the distribution of CDK9 and cyclin T1 such that they accumulate at the
      sites of AFF3/speckles. We demonstrate that AFF3 is a new target of Wnt/beta
      catenin pathway involved in ACC, acting on transcription and RNA splicing. 

PMID- 26214579
TI  - Inhibition of Light Chain 6aJL2-R24G Amyloid Fiber Formation Associated with
      Light Chain Amyloidosis.
AB  - Light chain amyloidosis (AL) is a deadly disease characterized by the deposition
      of monoclonal immunoglobulin light chains as insoluble amyloid fibrils in
      different organs and tissues. Germ line lambda VI has been closely related to
      this condition; moreover, the R24G mutation is present in 25% of the proteins of
      this germ line in AL patients. In this work, five small molecules were tested as
      inhibitors of the formation of amyloid fibrils from the 6aJL2-R24G protein. We
      have found by thioflavin T fluorescence and transmission electron microscopy that
      EGCG inhibits 6aJL2-R24G fibrillogenesis. Furthermore, using nuclear magnetic
      resonance spectroscopy, dynamic light scattering, and isothermal titration
      calorimetry, we have determined that the inhibition is due to binding to the
      protein in its native state, interacting mainly with aromatic residues. 

PMID- 26214581
TI  - Conjunctival Leiomyosarcoma: A Report of Two Cases.
AB  - PURPOSE: Leiomyosarcoma is a common soft tissue tumor in the body. However,
      ocular leiomyosarcoma is rather uncommon. Herein, we describe the clinical and
      histopathological features of two cases of conjunctival leiomyosarcoma. There
      have only been three previously documented cases of conjunctival leiomyosarcoma.
      RESULTS: A 34-year-old male presented with a 2-year history of a whitish mass in
      the right eye. He underwent an incisional biopsy of the mass, which supported the
      diagnosis of leiomyosarcoma on histopathological examination. Computed tomography
      showed orbital extension of the mass, following which he underwent an eyelid
      sparing orbital exenteration of the right side. The second case was that of a 39
      year-old male, who had a history of a whitish limbal mass, which had been
      previously excised elsewhere. The pre-operative clinical photographs and
      histopathology slides of the excised mass were reviewed. A histopathological
      diagnosis of conjunctival leiomyosarcoma was established and due to base
      positivity, he was treated with plaque radiotherapy. Both the cases showed no
      tumor recurrence or systemic metastasis at one-year follow-up. CONCLUSION:
      Primary conjunctival leiomyosarcoma is uncommon. Appropriate treatment of the
      tumor is associated with good prognosis.

PMID- 26214580
TI  - Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or
      lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The
      GRAALL experience.
AB  - Central nervous system (CNS) thrombotic events are a well-known complication of
      acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments
      including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is
      still lacking in adult patients. We report on the clinical evolution of 22 CNS
      venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic
      lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia
      (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) )
      infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred
      after a median of 18 days (range: 11-31) when patients had received a median of
      three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a
      median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3
      D28), and 95% of them exhibited AT levels lower than 60%. There were no evident
      increase in hereditary thrombotic risk factors prevalence, and thrombosis
      occurred despite heparin prophylaxis which was performed in 90% of patients.
      Acquired AT deficiency was frequently detected in patients with l-ASP-based
      therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less
      frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS
      thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One
      patient received all planned l-ASP infusions without recurrence of CNS thrombotic
      whereas l-ASP injections were discontinued in 20 patients during the management
      of thrombosis without a significant impact on overall survival (P = 0.4).

PMID- 26214582
TI  - Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression.
AB  - Liver sinusoidal endothelial cells (LSECs) are involved in the transport of
      nutrients, lipids, and lipoproteins, and LSEC injury occurs in various liver
      diseases including nonalcoholic fatty liver disease (NAFLD). However, the
      association between LSEC injury and NAFLD progression remains elusive.
      Accordingly, in this study, we aimed to elucidate the precise role of LSEC in the
      pathophysiology of NAFLD using two different mouse models, namely the choline
      deficient, L-amino acid-defined and high-fat diet models. Administration of these
      diets resulted in liver metabolic dysregulation mimicking human NAFLD, such as
      steatosis, ballooning, lobular inflammation, and fibrosis, as well as central
      obesity, insulin resistance, and hyperlipidemia. LSEC injury appeared during the
      simple steatosis phase, and preceded the appearance of activated Kupffer cells
      and hepatic stellate cells (HSCs). These results indicate that LSEC injury may
      have a 'gatekeeper' role in the progression from simple steatosis to the early
      nonalcoholic steatohepatitis (NASH) stage, and LSEC injury may be necessary for
      the activation of Kupffer cells and HSCs, which in turn results in the
      development and perpetuation of chronic liver injuries. Taken together, our data
      provide new insights into the role of LSEC injury in NAFLD/NASH pathogenesis. 

PMID- 26214583
TI  - HDAC is essential for epigenetic regulation of Thy-1 gene expression during
      LPS/TLR4-mediated proliferation of lung fibroblasts.
AB  - Lipopolysaccharide (LPS)-induced proliferation of lung fibroblasts is closely
      correlated with loss of gene expression of thymocyte differentiation antigen-1
      (Thy-1), accompanied with deacetylation of histones H3 and H4 at the Thy-1 gene
      promoter region; however, the mechanism remains enigmatic. We report here that
      LPS downregulates Thy-1 gene expression by activating histone deacetylases
      (HDACs) via Toll-like receptor 4 (TLR4) signaling. Treatment of primary cultured
      mouse lung fibroblasts with LPS resulted in significant upregulation of TLR4 and
      enhanced cell proliferation that was abolished by silencing TLR4 with lentivirus
      delivered TLR4 shRNA. Interestingly, LPS increased the mRNA and protein levels of
      HDAC-4, -5, and -7, an effect that was abrogated by HDAC inhibitor trichostatin A
      (TSA) or TLR4-shRNA-lentivirus. Consistent with these findings, Ace-H3 and Ace-H4
      were decreased by LPS that was prevented by TSA. Most importantly, chromosome
      immunoprecipitation (ChIP) analysis demonstrated that LPS decreased the
      association of Ace-H4 at the Thy-1 promoter region that was efficiently restored
      by pretreatment with TSA. Accordingly, LPS decreased the mRNA and protein levels
      of Thy-1 that was inhibited by TSA. Furthermore, silencing the Thy-1 gene by
      lentivirus-delivered Thy-1 shRNA could promote lung fibroblast proliferation,
      even in the absence of LPS. Conversely, overexpressing Thy-1 gene could inhibit
      lung fibroblast proliferation and reduce LPS-induced lung fibroblast
      proliferation. Our data suggest that LPS upregulates and activates HDACs through
      TLR4, resulting in deacetylation of histones H3 and H4 at the Thy-1 gene promoter
      that may contribute to Thy-1 gene silencing and lung fibroblast proliferation. 

PMID- 26214586
TI  - Condensation of Methane in the Metal-Organic Framework IRMOF-1: Evidence for Two
      Critical Points.
AB  - Extensive grand canonical Monte Carlo simulations in combination with successive
      umbrella sampling are used to investigate the condensation of methane in the
      nanoporous crystalline material IRMOF-1. Two different types of novel
      condensation transitions are found, each of them ending in a critical point: (i)
      a fluid-fluid transition at higher densities (the analog of the liquid-gas
      transition in the bulk) and (ii) a phase transition at low densities on the
      surface of the IRMOF-1 structure. The nature of these transitions is different
      from the usual capillary condensation in thin films and cylindrical pores where
      the coexisting phases are confined in one or two of the three spatial dimensions.
      In contrast to that, in IRMOF-1 the different phases can be described as bulk
      phases that are inhomogeneous due to the presence of the metal-organic framework.
      As a consequence, the condensation transitions in IRMOF-1 belong to the three
      dimensional (3D) Ising universality class. 

PMID- 26214587
TI  - Self-healing dynamic bond-based rubbers: understanding the mechanisms in
      ionomeric elastomer model systems.
AB  - While it is traditionally accepted that the chain interactions responsible for
      the elastic response in an elastomeric network are ideally permanent and
      instantaneously active, the ongoing investigation of self-healing materials
      reveals that the introduction of self-healing properties into elastomers requires
      high mechanical integrity under dynamic load conditions, while on long timescales
      (or at extended temperatures), the chain and bond dynamics must allow for an
      intrinsic repair of micro cracks occurring during operation and aging. Based on
      an acrylate-based amorphous ionomer model system with pendant carboxylate groups
      allowing the systematic variation of the composition and the nature of the
      counter ion, we demonstrate the interrelation between the morphological, thermal,
      and mechanical properties, and identify the prerequisites and tools for property
      adjustment and optimization of self-healing efficiency. While the ion fraction is
      directly related to the effective network density and elastic performance, the
      crossover frequency between viscous and elastic behavior is influenced by the
      nature of the counter ion. In order to achieve reliable elastic response and
      optimal damage repair, the ion fraction in these systems should be in the range
      of 5 mol% and the chain dynamics should be appropriate to allow for excellent
      self-healing behavior at moderate healing temperatures. 

PMID- 26214584
TI  - Enhancing eNOS activity with simultaneous inhibition of IKKbeta restores vascular
      function in Ins2(Akita+/-) type-1 diabetic mice.
AB  - The balance of nitric oxide (NO) versus superoxide generation has a major role in
      the initiation and progression of endothelial dysfunction. Under conditions of
      high glucose, endothelial nitric oxide synthase (eNOS) functions as a chief
      source of superoxide rather than NO. In order to improve NO bioavailability
      within the vessel wall in type-1 diabetes, we investigated treatment strategies
      that improve eNOS phosphorylation and NO-dependent vasorelaxation. We evaluated
      methods to increase the eNOS activity by (1) feeding Ins2(Akita) spontaneously
      diabetic (type-1) mice with l-arginine in the presence of sepiapterin, a
      precursor of tetrahydrobiopterin; (2) preventing eNOS/NO deregulation by the
      inclusion of inhibitor kappa B kinase beta (IKKbeta) inhibitor, salsalate, in the
      diet regimen in combination with l-arginine and sepiapterin; and (3)
      independently increasing eNOS expression to improve eNOS activity and associated
      NO production through generating Ins2(Akita) diabetic mice that overexpress human
      eNOS predominantly in vascular endothelial cells. Our results clearly
      demonstrated that diet supplementation with l-arginine, sepiapterin along with
      salsalate improved phosphorylation of eNOS and enhanced vasorelaxation of
      thoracic/abdominal aorta in type-1 diabetic mice. More interestingly, despite the
      overexpression of eNOS, the in-house generated transgenic eNOS-GFP (TgeNOS-GFP)
      Ins2(Akita) cross mice showed an unanticipated effect of reduced eNOS
      phosphorylation and enhanced superoxide production. Our results demonstrate that
      enhancement of endogenous eNOS activity by nutritional modulation is more
      beneficial than increasing the endogenous expression of eNOS by gene therapy
      modalities. 

PMID- 26214585
TI  - Virtual Screening for UDP-Galactopyranose Mutase Ligands Identifies a New Class
      of Antimycobacterial Agents.
AB  - Galactofuranose (Galf) is present in glycans critical for the virulence and
      viability of several pathogenic microbes, including Mycobacterium tuberculosis,
      yet the monosaccharide is absent from mammalian glycans. Uridine 5'-diphosphate
      galactopyranose mutase (UGM) catalyzes the formation of UDP-Galf, which is
      required to produce Galf-containing glycoconjugates. Inhibitors of UGM have
      therefore been sought, both as antimicrobial leads and as tools to delineate the
      roles of Galf in cells. Obtaining cell permeable UGM probes by either design or
      high throughput screens has been difficult, as has elucidating how UGM binds
      small molecule, noncarbohydrate inhibitors. To address these issues, we employed
      structure-based virtual screening to uncover new inhibitor chemotypes, including
      a triazolothiadiazine series. These compounds are among the most potent
      antimycobacterial UGM inhibitors described. They also facilitated determination
      of a UGM-small molecule inhibitor structure, which can guide optimization. A
      comparison of results from the computational screen and a high-throughput
      fluorescence polarization (FP) screen indicated that the scaffold hits from the
      former had been evaluated in the FP screen but missed. By focusing on promising
      compounds, the virtual screen rescued false negatives, providing a blueprint for
      generating new UGM probes and therapeutic leads. 

PMID- 26214588
TI  - 2'-O-[(4-CF3-triazol-1-yl)methyl] Uridine - A Sensitive (19)F NMR Sensor for the
      Detection of RNA Secondary Structures.
AB  - A sensitive uridine-derived sensor (viz., 2'-O-[(4-CF3-triazol-1
      yl)methyl]uridine, 1) for (19)F NMR spectroscopic monitoring of RNA secondary
      structures is described. The applicability of 1 is demonstrated by monitoring the
      thermal denaturation of the following double and triple helical RNA models: (1) a
      miR 215 hairpin, (2) a poly U-A*U triple helix RNA (bearing two C-G*C(H+)
      interrupts), and (3) a polyadenylated nuclear-nuclear retention element complex.
      In these RNA models, the (19)F NMR shift of the 2'-O-(CF3-triazolylmethyl) group
      shows high sensitivity to secondary structural arrangements. Moreover, 1 favors
      the desired N-conformation, and its effect on both RNA duplex and triplex
      stabilities is marginal. 

PMID- 26214589
TI  - Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a
      GGAA microsatellite.
AB  - Deciphering the ways in which somatic mutations and germline susceptibility
      variants cooperate to promote cancer is challenging. Ewing sarcoma is
      characterized by fusions between EWSR1 and members of the ETS gene family,
      usually EWSR1-FLI1, leading to the generation of oncogenic transcription factors
      that bind DNA at GGAA motifs. A recent genome-wide association study identified
      susceptibility variants near EGR2. Here we found that EGR2 knockdown inhibited
      proliferation, clonogenicity and spheroidal growth in vitro and induced
      regression of Ewing sarcoma xenografts. Targeted germline deep sequencing of the
      EGR2 locus in affected subjects and controls identified 291 Ewing-associated
      SNPs. At rs79965208, the A risk allele connected adjacent GGAA repeats by
      converting an interspaced GGAT motif into a GGAA motif, thereby increasing the
      number of consecutive GGAA motifs and thus the EWSR1-FLI1-dependent enhancer
      activity of this sequence, with epigenetic characteristics of an active
      regulatory element. EWSR1-FLI1 preferentially bound to the A risk allele, which
      increased global and allele-specific EGR2 expression. Collectively, our findings
      establish cooperation between a dominant oncogene and a susceptibility variant
      that regulates a major driver of Ewing sarcomagenesis. 

PMID- 26214590
TI  - Exome sequencing identifies recurrent mutations in NF1 and RASopathy genes in sun
      exposed melanomas.
AB  - We report on whole-exome sequencing (WES) of 213 melanomas. Our analysis
      established NF1, encoding a negative regulator of RAS, as the third most
      frequently mutated gene in melanoma, after BRAF and NRAS. Inactivating NF1
      mutations were present in 46% of melanomas expressing wild-type BRAF and RAS,
      occurred in older patients and showed a distinct pattern of co-mutation with
      other RASopathy genes, particularly RASA2. Functional studies showed that NF1
      suppression led to increased RAS activation in most, but not all, melanoma cases.
      In addition, loss of NF1 did not predict sensitivity to MEK or ERK inhibitors.
      The rebound pathway, as seen by the induction of phosphorylated MEK, occurred in
      cells both sensitive and resistant to the studied drugs. We conclude that NF1 is
      a key tumor suppressor lost in melanomas, and that concurrent RASopathy gene
      mutations may enhance its role in melanomagenesis. 

PMID- 26214593
TI  - Hydrogen-doping induced reduction in the phase transition temperature of VO2: a
      first-principles study.
AB  - VO2 is a promising thermochromic material that can intelligently control the
      transmittance of sunlight in the near-infrared region in response to temperature
      change, although the high phase transition temperature (Tc) of 340 K restricts
      its wide application. Our first-principles calculations show that hydrogen is an
      efficient dopant which can stabilize the metallic VO2 phase at ambient
      temperature through reducing Tc by 38 K/at% H. The reduction in Tc is coupled
      with the changes in atomic and electronic structures, i.e., the V-V chains
      feature the dimerization characteristics in H-doped VO2(R) and the V-O bonds
      become less ionic due to the formation of a typical H-O covalent bond. In
      addition, hydrogen-doped VO2 is more sensitive to external strain as compared
      with pure VO2, implying that Tc can be further regulated through a combination of
      H-doping and strain. 

PMID- 26214594
TI  - Dynamics of quiet human stance: computer simulations of a triple inverted
      pendulum model.
AB  - For decades, the biomechanical description of quiet human stance has been
      dominated by the single inverted pendulum (SIP) paradigm. However, in the past
      few years, the SIP model family has been falsified as an explanatory approach.
      Double inverted pendulum models have recently proven to be inappropriate. Human
      topology with three major leg joints suggests in a natural way to examine triple
      inverted pendulum (TIP) models as an appropriate approach. In this study, we
      focused on formulating a TIP model that can synthesise stable balancing
      attractors based on minimalistic sensor information and actuation complexity. The
      simulated TIP oscillation amplitudes are realistic in vertical direction. Along
      with the horizontal ankle, knee and hip positions, though, all simulated joint
      angle amplitudes still exceed the measured ones about threefold. It is likely
      that they could be eventually brought down to the physiological range by using
      more sensor information. The TIP systems' eigenfrequency spectra come out as
      another major result. The eigenfrequencies spread across about 0.1 Hz...20 Hz.
      Our main result is that joint stiffnesses can be reduced even below statically
      required values by using an active hip torque balancing strategy. When reducing
      mono- and bi-articular stiffnesses further down to levels threatening dynamic
      stability, the spectra indicate a change from torus-like (stable) to strange
      (chaotic) attractors. Spectra of measured ground reaction forces appear to be
      strange-attractor-like. We would conclude that TIP models are a suitable starting
      point to examine more deeply the dynamic character of and the essential
      structural properties behind quiet human stance. Abbreviations and technical
      terms Inverted pendulum body exposed to gravity and pivoting in a joint around
      position of unstable equilibrium (operating point) SIP single inverted pendulum:
      one rigid body pivoting around fixation to the ground (external joint) DIP double
      inverted pendulum: two bodies; external and internal joint operate around
      instability TIP triple inverted pendulum: three bodies; external and both
      internal joints operate around instability QIP quadruple inverted pendulum: four
      bodies, foot replaces external joint; all three internal joints operate around
      instability Eigenfrequency characteristic frequency that a physical system is
      oscillating at when externally excited at a limited energy level DOF degree of
      freedom; in mechanics: linear displacement or angle or combination thereof Mono
      articular stiffness: coefficient of proportionality between mechanical
      displacement of a DOF and restoring force/torque component in the respective DOF
      Bi-articular stiffness coefficient of proportionality between mechanical
      displacement of a DOF and restoring force/torque component in another DOF GRF
      ground reaction force HAT segment including head, arms and trunk COM centre of
      mass COP centre of pressure in the plane of the force platform surface.

PMID- 26214595
TI  - Active Site of the NAD(+)-Reducing Hydrogenase from Ralstonia eutropha Studied by
      EPR Spectroscopy.
AB  - Pulsed ENDOR and HYSCORE measurements were carried out to characterize the active
      site of the oxygen-tolerant NAD(+)-reducing hydrogenase of Ralstonia eutropha.
      The catalytically active Nia-C state exhibits a bridging hydride between iron and
      nickel in the active site, which is photodissociated upon illumination. Its
      hyperfine coupling is comparable to that of standard hydrogenases. In addition, a
      histidine residue could be identified, which shows hyperfine and nuclear
      quadrupole parameters in significant variance from comparable histidine residues
      that are conserved in standard [NiFe] hydrogenases, and might be related to the
      O2 tolerance of the enzyme. 

PMID- 26214596
TI  - N-heterocyclic carbene-palladium(II)-1-methylimidazole complex catalyzed alpha
      arylation reactions of tetralones with aryl chlorides and further transformation
      of the products.
AB  - NHC-Pd(II)-Im complex 1 has proven to be an efficient catalyst in the reaction
      between tetralones 2 and aryl chlorides 3, giving the alpha-arylated tetralones 4
      in good to high yields. In addition, if the above reaction mixture was exposed to
      air at room temperature for another 3 h, the normal alpha-arylated products 4 can
      be fully oxidized to 2-aryl-2'-hydroxytetralones 6 in good yields in a one-pot
      procedure. Furthermore, if the reaction mixture containing the oxidized products
      6 was treated with TsOH/toluene solution under reflux for 19 h, the final
      aromatized products, 2-aryl-naphthalen-1-ols 5 can be achieved in acceptable to
      moderate yields. All reactions can tolerate various substituents on the
      tetralones 2 and aryl chlorides 3, thus giving an efficient method for the alpha
      arylation of tetralones and further transformation of the products, and also
      enriching the applications of NHC-Pd(II) complexes in organic synthesis.

PMID- 26214592
TI  - Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic
      leukemia identifies recurrent mutation patterns and therapeutic options.
AB  - TCF3-HLF-positive acute lymphoblastic leukemia (ALL) is currently incurable.
      Using an integrated approach, we uncovered distinct mutation, gene expression and
      drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1
      positive ALL. We identified recurrent intragenic deletions of PAX5 or VPREB1 in
      constellation with the fusion of TCF3 and HLF. Moreover somatic mutations in the
      non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF
      ALL suggest cooperation within a restricted genetic context. The enrichment for
      stem cell and myeloid features in the TCF3-HLF signature may reflect
      reprogramming by TCF3-HLF of a lymphoid-committed cell of origin toward a hybrid,
      drug-resistant hematopoietic state. Drug response profiling of matched patient
      derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance
      to conventional chemotherapeutics but sensitivity to glucocorticoids,
      anthracyclines and agents in clinical development. Striking on-target sensitivity
      was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This
      integrated approach thus provides alternative treatment options for this deadly
      disease. 

PMID- 26214597
TI  - Development of a quantitative GC-FID method for the determination of sucrose mono
      and diesters in foods.
AB  - Sucrose esters (E 473) are emulsifiers used in foods to improve different
      technological properties. They should conform to the specifications laid down in
      Commission Regulation No. 231/2012 and be used at amounts not exceeding the
      maximal ones set by Commission Regulation No. 1129/2011. In order to be able to
      characterise commercial sucrose ester formulations and to evaluate whether they
      are used correctly by the food industry, a quantitative GC-FID method was
      developed. Standards of monoesters and diesters were isolated from commercial
      additive preparations because no commercial ones were available. Commercial
      sucrose monolaureate and in-house-synthesised sucrose diarachidonate were used as
      internal standards. The method showed limits of detection and quantification of
      2.9 and 5.7 ug ml(-1) respectively for the monoesters and 42.8 and 129.7 ug ml(
      1) respectively for the diesters. The analysed commercial additive formulations
      contained mainly mono- and diesters of palmitic and stearic acid with low amounts
      of free fatty acid and sucrose. Different food matrices were incurred with
      commercial sucrose esters formulations and recoveries ranged between 92% and 118%
      for the monoesters and between 77% and 120% for the diesters. Recovery of sucrose
      monoesters in cake was around 34% when no enzymatic treatment was applied, and
      about 64% when enzymatic treatment with Clara-Diastase was applied. This
      indicated that sucrose esters can interact strongly with the matrix during food
      production and that treatment with enzymes is essential to determine the esters'
      content accurately in some classes of food products.

PMID- 26214598
TI  - New guidance is needed on diagnosing microcephaly in severely malnourished
      children.

PMID- 26214599
TI  - Extraction and composition characterisation of amino acids from tung meal.
AB  - The most desirable content of amino acids (AAs) in the extracted products from
      tung (Aleurites fordii) meal was 93.88%, which was obtained from shelled tung
      meal at a hydrolysis temperature of 45  degrees C and a isoelectric precipitation
      pH value of 4.4. Furthermore, the cytotoxic activity of extracted AAs was also
      evaluated by MTT assay. Antioxidant activity of extracted AAs was also measured
      by the DPPH assay. As a result, the high yield of extracted AAs exhibited so low
      cytotoxic and high antioxidant activity that had the potential use as a
      functional ingredient.

PMID- 26214591
TI  - Analysis of mammalian gene function through broad-based phenotypic screens across
      a consortium of mouse clinics.
AB  - The function of the majority of genes in the mouse and human genomes remains
      unknown. The mouse embryonic stem cell knockout resource provides a basis for the
      characterization of relationships between genes and phenotypes. The EUMODIC
      consortium developed and validated robust methodologies for the broad-based
      phenotyping of knockouts through a pipeline comprising 20 disease-oriented
      platforms. We developed new statistical methods for pipeline design and data
      analysis aimed at detecting reproducible phenotypes with high power. We acquired
      phenotype data from 449 mutant alleles, representing 320 unique genes, of which
      half had no previous functional annotation. We captured data from over 27,000
      mice, finding that 83% of the mutant lines are phenodeviant, with 65%
      demonstrating pleiotropy. Surprisingly, we found significant differences in
      phenotype annotation according to zygosity. New phenotypes were uncovered for
      many genes with previously unknown function, providing a powerful basis for
      hypothesis generation and further investigation in diverse systems. 

PMID- 26214601
TI  - Tuning of fluorine content in graphene: towards large-scale production of
      stoichiometric fluorographene.
AB  - The availability of well-defined modified graphene derivatives such as
      fluorographene, graphane, thiographene or hydroxygraphene is of pivotal
      importance for tuning the resulting material properties in numerous potential
      applications. A series of fluorinated graphene with various contents of fluorine
      was synthesized by a simple fluorination procedure in an autoclave with a
      nitrogen/fluorine atmosphere at different exposure times and temperatures. To
      investigate the composition, structure and properties all samples were
      characterized in detail by a number of analytical techniques such as SEM, XRD,
      EDS, AFM, STEM, combustible elemental analysis, STA, XPS, Raman spectroscopy, UV
      VIS spectroscopy and cyclic voltammetry. The fully fluorinated graphene with the
      overall stoichiometry C1F1.05 had a bright white color indicating a significant
      change of band-gap. In comparison to other samples such a high concentration of
      fluorine led to the occurrence of exotic thermal behavior, strong luminescence in
      the visible spectral region and also the unique super-hydrophobic behavior
      observed on the material surface. The described tunable fluorination should pave
      the way to fluorographene based devices with tailored properties. 

PMID- 26214600
TI  - Chronic Cadmium Exposure Lead to Inhibition of Serum and Hepatic Alkaline
      Phosphatase Activity in Wistar Rats.
AB  - Alkaline phosphatase (ALP) activity in the serum and liver from rats administered
      with cadmium (Cd) in drinking water was studied. After metal administration, Cd
      showed a time-dependent accumulation in the liver, meanwhile metallothionein had
      a maximum increase at 1 month, remaining in this level until the end of the
      study. On the other hand, serum and liver ALP activity was decreased after 3
      months exposure. To determine if Cd produced an inhibition on enzyme, apo-ALP
      prepared from both nonexposed and exposed rats was reactivated with Zn, showing
      60% more activity as compared with the enzyme isolated from nonexposed rats. In
      vitro assays showed that Cd-ALP was partially reactivated with Zn; however, in
      the presence of cadmium, Zn-ALP was completely inhibited. Kinetic studies
      indicate a noncompetitive inhibition by Cd; these results suggest that Cd can
      substitute Zn, and/or Cd can interact with nucleophilic ligands essential for the
      enzymatic activity. 

PMID- 26214602
TI  - Phase dependent thermal and spectroscopic responses of Al2O3 nanostructures with
      different morphogenesis.
AB  - In this review, we discuss new developments and recent trends in both amorphous
      and crystalline Al2O3 oxide nanofluids related to their phase dependent
      characteristics in detail. Nowadays, nanofluids have gained significant attention
      with the enhanced energy/heat efficiency, which is highly desirable to improve
      the performance of any energy based devices and technology. This review article
      systematically describes the various chemical synthesis routes followed by bottom
      up approaches, surface morphologies, and detailed microstructure characteristics,
      and phase dependent thermal as well as optical properties for potential use of
      such materials in various applications. 

PMID- 26214603
TI  - Engineering polypeptide folding through trans double bonds: transformation of
      miniature beta-meanders to hybrid helices.
AB  - Utilization of conjugated double bonds to engineer the novel folded miniature
      beta-meander type structures, single step transformation of miniature beta
      meanders into alphaalphagamma(4)-hybrid peptide 10/12-helices using catalytic
      hydrogenation, their solution and single crystal conformations are reported. 

PMID- 26214604
TI  - Logic Models--Tools to Bridge the Theory-Research-Practice Divide.

PMID- 26214605
TI  - Non-alcoholic fatty liver disease as a consequence of autonomic imbalance and
      circadian desynchronization.
AB  - The circadian system, headed by the suprachiasmatic nucleus, synchronizes
      behaviour and metabolism according to the external light-dark cycle through
      neuroendocrine and autonomic signals. Metabolic diseases, such as steatosis,
      obesity and glucose intolerance, have been associated with conditions of
      circadian misalignment wherein the feeding schedule has been moved to the resting
      phase. Here we describe the physiological processes involved in liver lipid
      accumulation and show how they follow a circadian pattern importantly regulated
      by both the autonomic nervous system and the feeding-fasting cycle. We propose
      that an unbalanced activity of the sympathetic-parasympathetic branches between
      organs induced by circadian misalignment provides the conditions for the
      development and progression of non-alcoholic fatty liver disease. 

PMID- 26214606
TI  - Freestanding Ultrathin Metallic Nanosheets: Materials, Synthesis, and
      Applications.
AB  - Freestanding ultrathin metallic nanosheets (FUMNSs) with atomic thickness attract
      extensive attention because they display remarkable advantages over their bulk
      counterparts by virtue of their large specific area, high aspect ratio, and
      unsaturated surface coordination. The state of the art of research on FUMNSs is
      reviewed here, wherein the important progress from the aspects of material
      category, synthetic strategy, and practical application are introduced, and it is
      demonstrated that FUMNSs will play an important role in the fields of
      optoelectrics, catalysis, and magnetism. 

PMID- 26214607
TI  - Effects of bisphosphonates to treat osteoporosis in children with cerebral palsy:
      a meta-analysis.
AB  - BACKGROUND: In childhood and adolescence, some patients with cerebral palsy (CP)
      have long-term limited mobility, which can lead to secondary osteoporosis,
      Prevention and treatment strategies have been evaluated for the management of low
      bone mineral density (BMD) and fragility fractures. Currently, however, there are
      no established guidelines for the stratification and individualization of
      therapeutic interventions. Recently, an increasing number of studies have
      reported on the use of bisphosphonates to increase BMD in various pediatric
      conditions, and bisphosphonates have been suggested as a method to treat
      osteoporosis and prevent fractures. PURPOSE: We performed the current meta
      analysis to assess the effects of bisphosphonates on increasing BMD in children
      who have CP with secondary osteoporosis. MATERIALS AND METHODS: A search of
      PubMed, Cochrane, and Embase from inception to April 2014 was performed with the
      following keywords: (bone disease, metabolic OR osteoporosis OR osteopenia) AND
      (child OR pediatric OR adolescent) AND (cerebral palsy) AND (bisphosphonate).
      Four studies were ultimately included in the meta-analysis: one randomized,
      double-blinded, placebo-controlled study and three case-controlled studies.
      RESULTS: The Z-score of lumbar spine was significantly improved after
      bisphosphonates treatment compared with pre-treatment values (standardized mean
      difference [SMD], 0.799; 95% confidence interval [CI], 0.499-1.100; p<0.001). The
      Z-score of femur was also improved significantly compared with that of the
      baseline value (SMD, 0.748; 95% CI, 0.382-1.114; p<0.001). CONCLUSIONS:
      Bisphosphonates have a significant effect on improving BMD in children with CP.
      Further standardization of treatment protocols including treatment dosage and
      duration needs to be established, and long-term follow up studies are needed.

PMID- 26214608
TI  - Chemical composition, antitumor activity, and toxicity of essential oil from the
      leaves of Lippia microphylla.
AB  - The chemical composition, antitumor activity and toxicity of the essential oil
      from Lippia microphylla leaves (OEL) were investigated. The major constituents
      were thymol (46.5%), carvacrol (31.7%), p-cymene (9%), and gamma-terpinene
      (2.9%). To evaluate the toxicity of OEL in non-tumor cells, the hemolytic assay
      with Swiss mice erythrocytes was performed. The concentration producing 50%
      hemolysis (HC50) was 300 MUg/mL. Sarcoma 180 tumor growth was inhibited in vivo
      38% at 50 mg/kg, and 60% at 100 mg/kg, whereas 5-FU at 50 mg/kg caused 86%
      inhibition. OEL displays moderate gastrointestinal and hematological toxicity
      along with causing some alteration in liver function and morphology. However, the
      changes were considered reversible and negligible in comparison to the effects of
      several anticancer drugs. In summary, OEL displays in vivo antitumor activity and
      a moderate toxicity, which suggests further pharmacological study. 

PMID- 26214609
TI  - Assessment of the impacts of traditional Persian medical schemes and
      recommendations on functional chronic constipation compared to a classic medicine
      lactulose, a randomized clinical trial.
AB  - BACKGROUND: To manage chronic constipation, numerous lifestyle modification
      schemes and recommendations as well as applications of natural medicaments have
      been mentioned in manuscripts of traditional Persian medicine (TPM). This study
      was aimed to compare the impacts of some of those recommendations with lactulose,
      on functional chronic constipation. METHODS: Via a blocked randomization, 100
      patients were enrolled. Schemes and recommendations from TPM as intervention
      group were evaluated versus lactulose as control by weekly follow-ups with
      standard questionnaire for 3 months. Stool frequency, hard stool, painful
      defecation, incomplete evacuation sensation, anorectal obstruction sensation and
      manual maneuvers were considered as outcome measures. RESULTS: Eighty-six
      patients (42 in schemes and 44 in lactulose groups) completed the study. Median
      weekly stool frequency in 0, 4, 8 and 12 weeks of treatment was 1.76+/-1.79,
      2.88+/-0.89, 2.95+/-1.05 and 2.93+/-1.11 in the schemes and 2.41+/-1.67, 2.57+/
      0.90, 2.84+/-0.91 and 2.77+/-1.00 in lactulose groups, respectively (p=0.10,
      0.11, 0.60, 0.51). Thirty-two (76.2%) patients in schemes and 24 (54.5%) patients
      in lactulose groups were treated at the end of the protocol as they did not meet
      the Rome III criteria for constipation (p=0.04). In schemes group, patients
      reported no undesirable effects, whereas seven (15.9%) in lactulose group
      reported flatulence (p=0.02). CONCLUSIONS: Studied schemes were as effective as
      lactulose, a gold standard to manage constipation. Results demonstrated that TPM
      schemes and recommendations, as lifestyle modification, for at least 3 months can
      be introduced as cheap, available and accessible approaches for the management of
      constipation.

PMID- 26214610
TI  - Newtonoate as an active principle of Newtonia griffoniana for anxiolytic activity
      in Swiss mice.
AB  - BACKGROUND: Newtonia griffoniana (Mimosaceae) is a Central African rain forest
      tree, whose bark extracts are used in Cameroonian folk medicine for the treatment
      of anxiety and sleep disorders. METHODS: We evaluated the anxiolytic effects of
      N. griffoniana stem bark methanol extract and its major isolated constituent
      2,3,4-trihydroxybutylpentatriacontanoate (newtonoate) on the elevated plus maze.
      RESULTS: Significant increases in the percentage of entries into open arms were
      induced by both N. griffoniana extract (100 and 150 mg/kg BW; p<0.01) and
      newtonoate (doses of 3 and 15 mg/kg BW; p<0.05). Conversely, decreases in the
      percentage of entries into closed arms were observed at the same doses. In
      addition, N. griffoniana methanol extract (100 mg/kg) and the isolated newtonoate
      (30 mg/kg) induced significant (p<0.01 and p<0.05, respectively) increases in the
      time spent in the open arms, while inducing a decrease in the time spent in the
      closed arms. Newtonoate treatment also decreased head dipping number at doses of
      3 and 15 mg/kg, while N. griffoniana methanol extract induced the same effect at
      200 mg/kg. CONCLUSIONS: These results suggest that N. griffoniana bark extract
      has anxiolytic properties, which justify its use in folk medicine. Such effects
      are at least partly mediated by newtonoate.

PMID- 26214611
TI  - Predictive factors of persistent infantile atopic dermatitis up to 6 years old in
      Taiwan: a prospective birth cohort study.
AB  - BACKGROUND: Atopic dermatitis affects 15-30% of children worldwide. Onset of
      disease usually occurs within the first year of life, over half of which regress
      by 6 years of age. The aim of this study was to investigate the risk factors
      related to the persistence of infantile atopic dermatitis. METHODS: In this birth
      cohort study, patients were enrolled prenatally and followed until 6 years of
      age; 246 patients had infantile atopic dermatitis at 6 months of age. Family
      history, maternal and paternal total and specific Immunoglobulin E (IgE) levels,
      and cord blood IgE were recorded. Clinical examination, questionnaire survey, and
      blood samples for total and specific IgE of the children were collected at each
      follow-up visit. RESULTS: Of the 246 patients with infantile atopic dermatitis at
      6 months of age, 48 patients had persisted atopic dermatitis at 6 years of age
      (19.5%). Risk factors associated with persistent infantile atopic dermatitis
      included egg white sensitization (odds ratio: 3.801, P = 0.020), and atopic
      dermatitis involving two or more areas at 6 months old (odds ratio: 2.921, P =
      0.018) after multivariate analysis with logistic regression. Patients with
      persistent infantile atopic dermatitis had a higher risk of asthma before 6 years
      old (39.6% vs 24.2%, P = 0.032). CONCLUSION: Egg white sensitization and the
      initial involvement of two or more areas at 6 months of age were associated with
      the persistent infantile atopic dermatitis. Patients with persistent infantile
      atopic dermatitis are more likely to develop asthma by 6 years of age.

PMID- 26214612
TI  - Attitudes and Perceptions About Smoking Cessation in the Context of Lung Cancer
      Screening.
AB  - IMPORTANCE: Broad adoption of lung cancer screening may inadvertently lead to
      negative population health outcomes if it is perceived as a substitute for
      smoking cessation. OBJECTIVE: To understand views on smoking cessation from
      current smokers in the context of being offered lung cancer screening as a
      routine service in primary care. DESIGN, SETTING, AND PARTICIPANTS: As an
      ancillary study to the launch of a lung cancer screening program at 7 sites in
      the Veterans Health Administration, 45 in-depth semi-structured qualitative
      interviews about health beliefs related to smoking and lung cancer screening were
      administered from May 29 to September 22, 2014, by telephone to 37 current
      smokers offered lung cancer screening by their primary care physician. Analysis
      was conducted from June 15, 2014, to March 29, 2015. MAIN OUTCOMES AND MEASURES:
      Attitudes and perceptions about the importance of smoking cessation in the
      context of lung cancer screening. RESULTS: Lung cancer screening prompted most
      current smokers to reflect for the first time on what smoking means for their
      current and future health. However, 17 of 35 (49%) participants described
      mechanisms whereby screening lowered their motivation for cessation, including
      the perception that undergoing an imaging test yields the same health benefits as
      smoking cessation. Other misperceptions include the belief that everyone who
      participates in screening will benefit; the belief that screening and being able
      to return for additional screening offers protection from lung cancer; the
      perception by some individuals that findings from screenings have saved their
      lives by catching their cancer early when indeterminate findings are identified
      that can be monitored rather than immediately treated; and a reinforced belief in
      some individuals that a cancer-free screening test result indicates that they are
      among the lucky ones who will avoid the harms of smoking. CONCLUSIONS AND
      RELEVANCE: In this qualitative, lung cancer screening prompted many current
      smokers to reflect on their health and may serve as a potential opportunity to
      engage patients in discussions about smoking cessation. However, several
      concerning pathways were identified in which screening, when offered as part of
      routine care and described as having proven efficacy, may negatively influence
      smoking cessation. Health care professionals should be aware that the opportunity
      for early detection of lung cancer may be interpreted as a way of avoiding the
      harms of smoking. To promote cessation, discussions should focus on the emotional
      response to screening rather than clinical details (eg, nodule size) and address
      misperceptions about the value of early detection so that screening does not
      lower motivation to quit smoking.

PMID- 26214614
TI  - Determining adsorbate configuration on alumina surfaces with (13)C nuclear
      magnetic resonance relaxation time analysis.
AB  - Relative strengths of surface interaction for individual carbon atoms in acyclic
      and cyclic hydrocarbons adsorbed on alumina surfaces are determined using
      chemically resolved (13)C nuclear magnetic resonance (NMR) T1 relaxation times.
      The ratio of relaxation times for the adsorbed atoms T1,ads to the bulk liquid
      relaxation time T1,bulk provides an indication of the mobility of the atom. Hence
      a low T1,ads/T1,bulk ratio indicates a stronger surface interaction. The carbon
      atoms associated with unsaturated bonds in the molecules are seen to exhibit a
      larger reduction in T1 on adsorption relative to the aliphatic carbons,
      consistent with adsorption occurring through the carbon-carbon multiple bonds.
      The relaxation data are interpreted in terms of proximity of individual carbon
      atoms to the alumina surface and adsorption conformations are inferred.
      Furthermore, variations of interaction strength and molecular configuration have
      been explored as a function of adsorbate coverage, temperature, surface pre
      treatment, and in the presence of co-adsorbates. This relaxation time analysis is
      appropriate for studying the behaviour of hydrocarbons adsorbed on a wide range
      of catalyst support and supported-metal catalyst surfaces, and offers the
      potential to explore such systems under realistic operating conditions when
      multiple chemical components are present at the surface. 

PMID- 26214613
TI  - Endemic Mimosa species from Mexico prefer alphaproteobacterial rhizobial
      symbionts.
AB  - The legume genus Mimosa has > 500 species, with two major centres of diversity,
      Brazil (c. 350 spp.) and Mexico (c. 100 spp.). In Brazil most species are
      nodulated by Burkholderia. Here we asked whether this is also true of native and
      endemic Mexican species. We have tested this apparent affinity for
      betaproteobacteria by examining the symbionts of native and endemic species of
      Mimosa in Mexico, especially from the central highlands where Mimosa spp. have
      diversified. Nodules were tested for betaproteobacteria using in situ
      immunolocalization. Rhizobia isolated from the nodules were genetically
      characterized and tested for their ability to nodulate Mimosa spp. Immunological
      analysis of 25 host taxa suggested that most (including all the highland
      endemics) were not nodulated by betaproteobacteria. Phylogenetic analyses of 16S
      rRNA, recA, nodA, nodC and nifH genes from 87 strains isolated from 20 taxa
      confirmed that the endemic Mexican Mimosa species favoured alphaproteobacteria in
      the genera Rhizobium and Ensifer: this was confirmed by nodulation tests. Host
      phylogeny, geographic isolation and coevolution with symbionts derived from very
      different soils have potentially contributed to the striking difference in the
      choice of symbiotic partners by Mexican and Brazilian Mimosa species. 

PMID- 26214615
TI  - Evaluation of light scattering and absorption properties of in vivo rat liver
      using a single-reflectance fiber probe during preischemia, ischemia-reperfusion,
      and postmortem.
AB  - Diffuse reflectance spectroscopy (DRS) has been extensively used for
      characterization of biological tissues as a noninvasive optical technique to
      evaluate the optical properties of tissue. We investigated a method for
      evaluating the reduced scattering coefficient MU(s)', the absorption coefficient
      MU(a), the tissue oxygen saturation StO2, and the reduction of heme aa3 in
      cytochrome c oxidase CcO of in vivo liver tissue using a single-reflectance fiber
      probe with two source-collector geometries. We performed in vivo recordings of
      diffuse reflectance spectra for exposed rat liver during the ischemia-reperfusion
      induced by the hepatic portal (hepatic artery, portal vein, and bile duct)
      occlusion. The time courses of MU a at 500, 530, 570, and 584 nm indicated the
      hemodynamic change in liver tissue as well as StO2. Significant increase in
      MU(a)(605)/MU(a)(620) during ischemia and after euthanasia induced by nitrogen
      breathing was observed, which indicates the reduction of heme aa3, representing a
      sign of mitochondrial energy failure. The time courses of MU(s)' at 500, 530,
      570, and 584 nm were well correlated with those of MU(a), which also reflect the
      scattering by red blood cells. On the other hand, at 700 and 800 nm, a temporary
      increase in MU(s)' and an irreversible decrease in MU(s)' were observed during
      ischemia-reperfusion and after euthanasia induced by nitrogen breathing,
      respectively. The change in MU(s)' in the near-infrared wavelength region during
      ischemia is indicative of the morphological changes in the cellular and
      subcellular structures induced by the ischemia, whereas that after euthanasia
      implies the hepatocyte vacuolation. The results of the present study indicate the
      potential application of the current DRS system for evaluating the
      pathophysiological conditions of in vivo liver tissue.

PMID- 26214616
TI  - Optically-tracked handheld fluorescence imaging platform for monitoring skin
      response in the management of soft tissue sarcoma.
AB  - Standard clinical management of extremity soft tissue sarcomas includes surgery
      with radiation therapy. Wound complications (WCs) arising from treatment may
      occur due to bacterial infection and tissue breakdown. The ability to detect
      changes in these parameters during treatment may lead to earlier interventions
      that mitigate WCs. We describe the use of a new system composed of an
      autofluorescence imaging device and an optical three-dimensional tracking system
      to detect and coregister the presence of bacteria with radiation doses. The
      imaging device visualized erythema using white light and detected bacterial
      autofluorescence using 405-nm excitation light. Its position was tracked relative
      to the patient using IR reflective spheres and registration to the computed
      tomography coordinates. Image coregistration software was developed to spatially
      overlay radiation treatment plans and dose distributions on the white light and
      autofluorescence images of the surgical site. We describe the technology, its use
      in the operating room, and standard operating procedures, as well as demonstrate
      technical feasibility and safety intraoperatively. This new clinical tool may
      help identify patients at greater risk of developing WCs and investigate
      correlations between radiation dose, skin response, and changes in bacterial load
      as biomarkers associated with WCs.

PMID- 26214617
TI  - The role of CDCP1 (CUB domain-containing protein 1) and ADAM12 (a disintegrin and
      metalloproteinase 12) in ovarian cancer.
AB  - Ovarian cancer (OC) is the second most common gynecological cancer and the
      deadliest in industrialized countries, with poor outcomes that indicate an urgent
      need to provide a greater insight into the molecular mechanisms underlying OC.
      Insights into the complex tumor microenviroment show that besides tumor islets,
      OC biomarkers can derive from newly formed blood vessels that have endothelial
      cells with a different molecular signature in comparison with their normal
      counterparts. In this view, recent research has been able to highlight promising
      candidates such as CDCP1 and ADAM12. Our present review summarises their
      implications in cancer progression with a focus on OC. 

PMID- 26214618
TI  - HIF-1alpha in colorectal carcinoma: review of the literature.
AB  - Colorectal cancer (CRC) is the third most common cancer worldwide and despite the
      abundance of molecular pathways and markers continually being reported, the
      mortality rates remain high. Hypoxia inducible factor 1alpha (HIF-1alpha) plays a
      major role in the response of tumors to hypoxia, and contributes to tumor
      aggressiveness, invasiveness and resistance to radiotherapy and chemotherapy.
      Targeting HIF-1alpha is an attractive strategy, with the potential for disrupting
      multiple pathways crucial for tumor growth. In the current study, HIF-1alpha
      immunohistochemical expression in CRC is reviewed along with the relation to
      clinical outcome and prognosis. In addition, the significant correlation of HIF
      1alpha to vascular endothelial growth factor (VEGF) expression is reported, as
      well as the possible role of HIF-1alpha in predicting the therapeutic response to
      anti-EGFR therapies. Herein, an overview of the HIF-1alpha expression in CRC is
      presented. This review delineates the crucial role that HIF-1alpha plays in
      carcinogenesis, tumor angiogenesis and cancer progression. The evaluation of HIF
      1alpha in patient biopsies could be useful as a prognostic and/or predictive
      biomarker in personalized cancer treatment.

PMID- 26214619
TI  - Oral administration of antineoplastic agents: the challenges for healthcare
      professionals.
AB  - Recent progress in cancer treatment has increased the use of oral antineoplastic
      agents. It is now estimated that at least 25% of the existing antineoplastic
      agents are planned to be used as oral agents and this mode of administration is
      likely to increase in the coming years. The use of oral anti- neoplastic agents
      affects many aspects of cancer treatment, and despite advantages, it also poses
      challenges to health care professionals and patients, many of which refer to the
      adherence and safety. Low patient adherence demonstrates the need for better
      management and monitoring of patients on oral antineoplastic agents. Patient
      education is essential to maintain adherence to oral antineoplastic therapy,
      promoting a better understanding of the patient treatment regimen, treatment
      goals and potential side-effects, patient safety and implementation of self-care
      measurement. This article discusses the above-mentioned challenges, as well as
      the possibilities of patient and family education to improve adherence, outcomes
      of treatment and quality of life, and offers recommendations for practice and
      further research. 

PMID- 26214620
TI  - Current insights into the association of Nestin with tumor angiogenesis.
AB  - Tumor angiogenesis is regarded as a hallmark of cancer and provides an important
      target for therapy. Nestin is an intermediate filament protein (IF) originally
      recognized as a neural stem cell marker. Development and progression of cancer
      requires sustained angiogenesis, dependent on the proliferation and migration of
      endothelial cells which seem to be better portrayed by nestin expression in
      various malignancies such as central nervous system, gastro-intestinal cancers,
      malignant melanoma, lung, prostate or breast cancer. The purpose of the present
      review was to emphasize the insights into nestin expression in relation to tumor
      angiogenesis in different types of cancer. Current evidence suggests that nestin
      positivity in tumor cells reflects stem-like properties of those cells. Whether
      or not expressed in both tumor and endothelial cells, nestin overexpression might
      reflect the extent of angiogenesis and function as a molecular anti-angiogenic
      target for cancer. 

PMID- 26214621
TI  - Quercetin reverses tamoxifen resistance in breast cancer cells.
AB  - PURPOSE: To investigate the effect of quercetin on the reversal of tamoxifen
      resistance in breast cancer cells, and explore the underlying mechanism. METHODS:
      We established a tamoxifen-resistant breast cancer cell line (MCF-7Ca/TAM-R), and
      exposed it to different concentrations of quercetin (experimental group 1: 10
      MUM, group 2: 25 MUM, and group 3: 50MUM). Each group was further subdivided into
      2 subgroups: 1) simultaneous administration of quercetin and 4-hydroxytamoxifen
      (OHT); 2) sequential administration of quercetin (12-h induction) followed by
      OHT. No drug exposure and OHT alone were used as controls. We determined cell
      survival, apoptosis, and expression of ERalpha (estrogen receptor alpha) and Her
      2 (human epidermal growth factor receptor 2). RESULTS: With increasing dosage of
      quercetin, significant decrease in proliferation and increase in apoptosis was
      observed. Low concentrations of quercetin (10 MUM) had no effects. We found no
      significant difference between simultaneous and sequential mode of drug
      administration. Further, with increasing dosage of quercetin, we observed a
      gradual reduction in Her-2 expression and upregulation of ERalpha. Again, no
      difference in Her-2 and ERalpha protein levels between simultaneous and
      sequential drug administration was noticed. CONCLUSIONS: Proliferation inhibition
      and apoptosis in MCF-7Ca/TAM-R cells increase with increasing dosage of
      quercetin. This suggests that quercetin can reverse tamoxifen resistance in
      breast cancer cells. The underlying mechanism likely involves upregulation of
      ERalpha combined with downregulation of Her-2. However, this effect is
      independent of whether quercetin and tamoxifen are administered simultaneously or
      sequentially.

PMID- 26214622
TI  - Are neutrophil/lymphocyte ratio and platelet/lymphocyte ratio associated with
      prognosis in patients with HER2-positive early breast cancer receiving adjuvant
      trastuzumab?
AB  - PURPOSE: To investigate whether the pretreatment neutrophil lymphocyte ratio
      (NLR) and the platelet lymphocyte ratio (PLR) have any prognostic significance in
      patients with HER2-positive early breast cancer receiving adjuvant trastuzumab.
      METHODS: 187 patients were retrospectively analyzed. The patients were separated
      into two groups according to the mean value of NLR and PLR (low NLR<=2.38, high
      NLR>2.38; and low PLR<=161.28, high PLR>161.28, respectively). The relationship
      between pretreatment NLR, PLR and clinicopathological factors was investigated.
      Univariate and multivariate Cox regression analyses were performed. To evaluate
      survival rates, the Kaplan-Meier method with log rank test were used. RESULTS:
      The median duration of follow up was 26.0 months (range 6.0-84.0). In high NLR
      and PLR groups, the mean age was lower, tumor size was larger and the number of
      hormone receptor positive patients was higher. No statistically significant
      relationship was found between clinicopathological factors and both NLR and PLR
      groups. During follow up, the rate of relapse was 12.6% in the low NLR group,
      16.2 % in the high NLR group, 12.6% in the low PLR group and 15.8% in the high
      PLR group (p=non significant). Although median disease free survival (DFS) was
      shorter in the high NLR than in the low NLR group, the difference was not
      statistically significant (p=0.45). No statistically significant difference was
      found between high and low PLR groups with regard to median DFS and overall
      survival (OS) (p=0.76, p=0.29, respectively). CONCLUSION: We conclude that in
      HER2-positive early breast cancer patients receiving adjuvant trastuzumab with
      high pretreatment NLR, DFS was shorter. As for PLR, no effect either on DFS or on
      OS was registered. Prospective studies with larger number of patients are
      required in order to evaluate the prognostic effect of NLR and PLR in HER2
      positive breast cancer patients.

PMID- 26214623
TI  - Breast cancer in postmenopausal patients: Impact of age.
AB  - PURPOSE: We analyzed the significance of age together with other classic
      prognostic parameters on the course of breast cancer in postmenopausal patients.
      METHODS: Our study included 151 postmenopausal patients with primary breast
      cancer, of which 55% received adjuvant tamoxifen therapy and 45% did not receive
      any kind of therapy. Probabilities of disease-free interval (DFI) were estimated
      using the Kaplan-Meier method and were compared by the log-rank test. A p
      value<0.05 was considered as statistically significant. RESULTS: In the tamoxifen
      treated subgroup, patients with estrogen receptor (ER) or progesterone receptor
      (PR) concentration>=5 fmol/mg had favorable course of disease (p<0.01, p<0.04),
      respectively. Patients>=66 years of age had a worse disease course compared to
      those<66 years. Also, patients>=66 years with pT1 tumors had a worse disease
      course compared to those<66 years and pT1 tumors. This result was repeated in
      other groups as well. In pT2 (>=2 cm), ER-positive, PR-positive and invasive
      ductal carcinoma (IDC) subgroups, patients>=66 years always had a worse disease
      course compared to patients<66 years. In the untreated subgroup, patients with
      ER>=52 fmol/mg (p<0.01), tumors>=2 cm (p<0.01), IDC (p<0.01) type or >=56 years
      (p<0.04) had statistically more recurrences. Among patients>=56 years, those with
      ER-positive or pT2 tumors had shorter DFI compared to ER-negative or pT1.
      Positive correlation between ER, PR and age of patients was also shown in this
      subgroup (p<0.03, p<0.02). CONCLUSION: Age of patients, ER and PR are significant
      prognostic factors in the tamoxifen-treated subgroup. In the untreated subgroup
      relevant prognostic parameters are age, tumor size, histological type and ER. The
      above prognostic factors retained their value in the long-term follow up in both
      the investigated subgroups of patients.

PMID- 26214624
TI  - Importance of Ki-67 in human epidermal growth factor receptor 2 positive breast
      cancer.
AB  - PURPOSE: The aim of this study was to evaluate the importance of Ki-67 in Human
      Epidermal Growth Factor Receptor 2 (Her-2) positive breast cancer patients.
      METHODS: We reviewed the records of patients diagnosed with Her-2-positive non
      metastatic breast cancer between 2005 and 2011. Paraffin-embedded tissue samples
      were stained with MIB-1 mouse monoclonal antibody to find Ki-67 levels. Patients
      were grouped as low Ki-67<20% and high Ki-67>=20%. Demographic and clinical
      features were compared. RESULTS: One hundred and six patients were included in
      the study. Median follow up time was 41 months (range 15-100). Median age was
      49.5 years (range 29-79). Twenty-nine patients (27.4%) were in the Ki-67 low
      group. Demographic features were similar in both groups. Lymphovas cular invasion
      was more frequent in the Ki-67 high group, and hormone receptor (HR) positivity
      was more frequent in the Ki-67 low group (p=0.03, p=0.03, respectively).
      Recurrence rate was not significantly different in both groups (p=0.36). T stage
      (p=0.02), stage (p<0.01), lymphovascular invasion (p=0.02), ER status (p=0.02),
      and HR status (p<0.01) were related with recurrence. In multivariate analysis,
      stage and HR negativity were independent factors for recurrence (p<0.01, p=0.01,
      respectively). Recurrence sites were also similar in both groups. Survival rates
      at the third year for Ki-67 low group and Ki-67 high group were 94% and 92%,
      respectively. CONCLUSION: Her-2 positive patients with low Ki-67 and high Ki-67
      had similar demographic and pathologic features except lymphovascular invasion
      and HR status. HR status was an important factor for disease course. Clinical
      course was determined by HR status rather than Ki-67.

PMID- 26214625
TI  - The lymph node ratio as an independent prognostic factor for non-metastatic node
      positive breast cancer recurrence and mortality.
AB  - PURPOSE: To examine the prognostic value of lymph node ratio (LNR) in
      pathological nodal (pN) stage breast cancer patients. Also, to analyse additional
      clinical and pathologic prognostic factors and the impact of LNR among molecular
      subtypes. METHODS: Among a total of 3088 patients, 1004 women with non-metastatic
      lymph node-positive breast cancer were analysed. The patients were classified
      into low (<=0.20), intermediate (0.20 to 0.65) and high-risk (>0.65) LNR groups.
      Univariate and multivariate Cox proportional hazards regression model for disease
      free survival (DFS), and overall survival (OS) were performed to evaluate the
      prognostic value of LNR. RESULTS: The median LNR was 0.17 (range 0.02-1.00). Of
      the patients, 55.7% were in low, 32.1% in intermediate, and 12.3% in high risk
      group. When compared with low risk group, high risk group had more often large
      tumor size and high grade tumor with lymphovascular invasion. The median follow
      up period was 46.8 months. The 5-year breast cancer-specific OS and DFS rates for
      patients with low, intermediate, and high were 88%-67%, 65%-48% and 53%-24%,
      respectively (both plog-rank<0.0001). On multivariate analysis, pN stage and LNR
      were both independent predictors of survival, however, an overlapping between N1
      (250 months, 95% confidence interval [CI] 88.15-413.21) and N2 (176 months, 95%
      CI 129.51-222.93) curves in pN staging was determined. We also observed clear
      prognostic separation for triple negative breast cancer with LNR survival over pN
      staging. CONCLUSION: The LNR predicts survival more accurately than pN staging in
      node-positive breast cancer patients. The use of LNR may standardize the staging
      and guide decisions for adjuvant treatments.

PMID- 26214626
TI  - CALy Prognostic Score (CEA, ALP, Lymphocyte Count) as a predictor of survival
      after hepatectomy for liver-only colorectal metastases.
AB  - PURPOSE: The discovery of prognostic factors for patients who undergo hepatectomy
      for colorectal liver metastases (CRLM) in the era of neoadjuvant chemotherapy is
      imperative. This study aimed to establish a simple, cheap and easily available
      prognostic score for these patients. METHODS: Preoperative carcinoembryonic
      antigen (CEA), serum alkaline phosphatase (ALP), and lymphocyte count (LC) were
      used for the establishment of a prognostic score (CALy PS). The cut-off levels of
      these variables were determined by applying receiver operating curve (ROC)
      analysis. The final prognostic score assigned one risk point for each variable
      (CEA>4 MUg/L, ALP>93 U/L, and LC>=1.6x10(9)/L). RESULTS: One hundred and thirty
      five patients were included. Two risk categories were established with 0-1 and 2
      3 points, respectively. CALy 0-1 vs CALy 2-3, and CALy 2-3 were associated with
      decreased disease free survival (DFS) and overall survival (OS) both in
      univariate and multivariate analysis (DFS: HR 1.84; 95% CI 1.18-2.86; p=0.007;
      OS: HR 2.25; 95% CI 1.23-4.11; p=0.008). When four risk categories were
      established with 0,1,2,and 3 points,CALy was again associated with decreased DFS
      and OS both in univariate and in multivariate analysis (DFS: HR 1.37; 95% CI
      1.083-1.74; p=0.009; OS:HR 1.84; 95% CI 1.31-2.59; p<0.001). Three-year DFS rates
      for these categories (CALy 0, CALy 1, CALy 2, and CALy 3) were 45, 38, 15 and 7%,
      respectively, and the 5-year OS rates were 78, 68, 32, and 24%, respectively.
      CONCLUSION: This simple, cheap, and easily available risk score provides good
      prognostic accuracy for both DFS and OS for patients undergoing liver resection
      for liver-only colorectal metastases after neoadjuvant chemotherapy.

PMID- 26214627
TI  - Investigation of treatment methods in obstructive colorectal cancer.
AB  - PURPOSE: The aim of this study was to explore the treatment strategies for
      patients with obstructive colorectal cancer at different sites. METHODS:
      Treatment strategies were adopted according to the location of colorectal cancer
      and the condition of the patients when they were admitted to the hospital. Among
      a total of 134 patients, 29 patients were subjected to stent placement to relieve
      the obstruction before undergoing colorectal resection, 15 patients underwent per
      anum ileus catheterization to alleviate the symptoms of obstruction and waited
      for removal of the tumor within a limited time; 39 underwent intraoperative
      colonic lavage and colon resection with anastomosis and the remaining 51 patients
      were subjected to emergency surgery due to strangulation of the bowel,
      perforation, septic shock or other conditions before surgery. RESULTS: Stent
      placement was successfully performed on 23 patients, with a success rate of 79%.
      Ninety-five of 134 patients (71% had stage I anastomosis and only one case had
      anastomotic fistula. Infection of incision happened in 9 (7%) cases and 2 (1.5%)
      patients died of infection. CONCLUSIONS: Individualized treatment for patients
      with obstructive colorectal cancer can lead to tumor resection and stage I
      anastomosis, thereby avoiding the suffering of second-stage surgery or colostomy.

PMID- 26214628
TI  - Assessment and biological significance of JC polyomavirus in colorectal cancer in
      Tunisia.
AB  - PURPOSE: Several reports have indicated the presence of JC polyomavirus (JCV) in
      many human tumors, including colorectal cancers (CRCs). The presence of JCV
      infection in CRC patients has not been investigated in African countries.
      METHODS: We examined the prevalence and the biological significance of JCV in
      Tunisian CRC patients. The presence of JCV was assessed by polymerase chain
      reaction (PCR) in a series of 105 CRCs and 89 paired non-tumor colonic mucosa
      samples from Tunisian patients. Results were correlated with the
      clinicopathological features and immunohistochemical expression of beta-catenin,
      p53, and the proliferation marker Ki-67. RESULTS: JCV DNA was detected in 58.1%
      (61/105) of CRC and in only 14.6% (13/89) of paired non tumor colonic mucosa
      samples (p=0.03). The presence of JCV was significantly correlated with tumor
      differentiation (p=0.03). Moreover, JCV presence was significantly correlated
      with nuclear accumulation of beta-catenin (p=0.008) and p53 accumulation
      (p=0.0001). Multivariate logistic regression analysis showed that tumor
      differentiation, beta-catenin and p53 accumulation were independent parameters
      significantly associated with the presence of JCV in CRC (p=0.04; p=0.05;
      p=0.001, respectively). CONCLUSION: We support a role of JCV in colorectal
      carcinogenesis in Tunisian patients, especially of well differentiated
      morphology.

PMID- 26214629
TI  - Lack of associations between XPC polymorphisms and colorectal cancer: a meta
      analysis.
AB  - PURPOSE: The relationships between XPC polymorphisms (Lys939Gln and Ala499Val)
      and the susceptibility to colorectal cancer (CRC) have been studied by several
      researchers, but the results were inconclusive. To get a more precise estimation
      of the relationships, we conducted this meta-analysis. METHODS: A total of 9 case
      control studies, including 3679 cases and 33551 controls for Lys939Gln and 1327
      cases and 30438 controls for Ala499Val, were selected. Crude odds ratios (ORs)
      with 95% confidence intervals (CIs) were used to assess the strength of
      association in the additive, dominant and recessive models. RESULTS: When all the
      studies were pooled into the meta-analysis, no evidence showing a significant
      association between XPC polymorphisms and CRC risk was noticed. In the subgroup
      analysis by ethnicity and study design, no significant association was also
      found. CONCLUSION: In conclusion, this meta-analysis indicated that the XPC
      polymorphisms were not risk factors for the development of CRC.

PMID- 26214630
TI  - Important prognostic factors for the long-term survival in non-small cell lung
      cancer patients treated with combination of chemotherapy and conformal
      radiotherapy.
AB  - PURPOSE: Combined modality therapy is standard of care for patients with
      unresectable locally advanced non-small cell lung cancer (NSCLC), however,
      insufficient data exist regarding prognostic factors in this disease setting.
      METHODS: To evaluate the treatment results and prognostic variables, 85 NSCLC
      patients treated from October 2005 to April 2008 were randomly assigned to one of
      the two treatment arms. In the first arm (sequential arm), 45 patients received
      sequential chemotherapy with 4 cycles of carboplatin and etoposide followed by
      conformal 3-dimensional (3D) radiotherapy (RT). In the second arm (concurrent
      arm), 40 patients received concomitant chemotherapy with cisplatin and etoposide
      and conformal RT, followed by two cycles of consolidation chemotherapy with
      carboplatin and etoposide. RESULTS: The median survival was 13 months for the
      patients in the sequential arm and 19 months for those in the concurrent
      treatment arm (p=0.0039). The disease-free survival (DFS) was 9 months in the
      sequential arm and 16 months in the concurrent treatment arm (p=0.0023). The
      following prognostic factors significantly influenced the survival of the
      patients treated with combination of RT and chemotherapy: age (p<0.05),
      performance status (PS) (p<0.001), weight loss (p<0.001), tumor size (p<0.05),
      nodal involvement (p<0.05). CONCLUSIONS: Given the higher toxicity in the second
      arm, this should be reserved for younger patients (<70 years), having good PS and
      minimal weight loss. We highly recommend precise stage and prognostic factors
      definitions in such patients so that they receive the most beneficial treatment.

PMID- 26214631
TI  - An approach of selecting appropriate markers from the primary tumor to enable
      detection of circulating tumor cells in patients with non-small cell lung cancer.
AB  - PURPOSE: Circulating tumor cells (CTCs) are rare and difficult to isolate, and
      require selecting minimal but appropriate markers. The aim of this study was to
      identify markers in the primary non small cell lung cancer (NSCLC) tissue to
      guide isolation of CTCs from the peripheral blood of patients with lung cancer.
      METHODS: The expression of CK-19, EGFR and MUC-1 was evaluated by RT-PCR in the
      NSCLC tumor and paired adjacent normal tissues from 27 patients. The normal
      cytology, and the neoplastic and fibrotic pathology of the tissue were analyzed
      by histochemistry. The expression of the markers was analyzed in relation to the
      stage and grade of disease. RESULTS: Expression analysis showed that 42% of the
      tumors were positive for CK-19, whereas 85% for both EGFR and MUC-1. Ninety two
      percent of the tumors expressed any one marker. All (100%) adjacent normal
      tissues were CK-19 negative, 52% EGFR negative and 44% MUC-1 negative. CK-19
      expression was specific to the tumor tissue but it was expressed by only 42% of
      them, manifesting a need for at least three markers to guide the detection of
      CTCs isolated from the peripheral blood of NSCLC patients. Histopathology
      demonstrated that 58% were adenocarcinomas, 35% squamous cell carcinomas and 7%
      had mixed pathology. CONCLUSIONS: This data serves as a prelude and emphasizes
      the importance of selecting markers expressed in the primary tumor tissue to
      facilitate and enable enumeration of CTCs.

PMID- 26214632
TI  - Risk factors for recurrence in patients with resected N1 non-small cell lung
      cancer - a systematic review and meta-analysis.
AB  - PURPOSE: To evaluate the rates of locoregional failure (LRF) vs distant
      metastasis (DM), and find risk factors for recurrence in patients with completely
      resected N1 non-small cell lung cancer (NSCLC). METHODS: By searching Pubmed,
      Embase and the Cochrane Controlled Trials Register from 1995 through 2014,
      eligible randomized clinical trials (RCTs) were identified. In addition, the
      reference lists of articles and conference abstracts were searched. The logarithm
      of the risk ratio (RR) and its standard error (SE) were calculated, and a fixed
      effect model was used to combine the estimates. RESULTS: 3 RCTs and 9
      retrospective studies, which included 889 patients, were identified and selected.
      All studies dealt with resected N1 NSCLC, LRF vs DM, and risk factors such as
      visceral pleural invasion (VPI) and lymphovascular invasion (LVI). There was
      statistically significant benefit on 5-year overall survival (OS) for LRF
      (RR=0.68,95% CI=0.60-0.78, p<0.00001). Further analysis for patients with LRF
      also showed that VPI (RR=1.25, 95% confidence interval/CI=1.09-1.42, p=0.0009),
      LVI (RR=1.16, 95% CI=1.04-1.30, p=0.009), were the main risk factors for
      recurrence. CONCLUSIONS: The present study indicates that in patients with
      resected N1 NSCLC, the incidence of LRF is lower than DM. Advanced T stage
      classification, VPI, and LVI were predictors of poor survival. These patients
      represent a subgroup with N1 disease who might benefit from additional therapy,
      including adjuvant radiotherapy (RT). However, large, well-designed prospective
      studies should be conducted to confirm this conclusion.

PMID- 26214633
TI  - Early initiation of fluorouracil-based adjuvant chemotherapy improves survival in
      patients with resectable gastric cancer.
AB  - PURPOSE: Several clinical trials have suggested that adjuvant chemotherapy
      improves the survival of patients with resected gastric cancer, but the optimal
      time at which to initiate post-operative adjuvant chemotherapy has not been
      studied. This study investigated the association between time to adjuvant
      chemotherapy and survival in gastric cancer. METHODS: We retrospectively
      identified 266 patients with stage IB-IIIC gastric cancer who received
      fluorouracil-based adjuvant chemotherapy after radical gastrectomy. Overall
      survival (OS) was compared between patients grouped according to time from
      surgery to adjuvant chemotherapy (<45 and >=45 days). The Cox proportional
      hazards model was used to analyze the effects of time to initiation of
      chemotherapy and other clinical covariates on survival. RESULTS: Of 266 patients,
      141 (53%) started adjuvant chemotherapy within 45 days after surgery and 125
      (47%) started adjuvant chemotherapy more than 45 days after surgery. The 3-year
      OS rates were 81.2 and 65.8% for patients starting chemotherapy within 45 days
      and after 45 days, respectively (p=0.006). Multivariate analysis identified early
      initiation of adjuvant chemotherapy, completion of the planned chemotherapy, and
      early-stage disease as favorable prognostic factors in terms of OS (p<0.05).
      Subgroup analysis suggested that starting chemotherapy within 45 days after
      surgery was associated with significant OS benefit compared with initiation of
      chemotherapy after 45 days from surgery in most subgroups. CONCLUSIONS: This
      retrospective analysis suggests that delaying adjuvant chemotherapy for longer
      than 45 days after surgery may be associated with poorer survival in patients
      with resected gastric cancer.

PMID- 26214634
TI  - Revisiting post-gastrectomy anemia with a brief survey among a group of Turkish
      medical oncologists.
AB  - PURPOSE: Total or subtotal gastrectomy are performed as curative or palliative
      treatment in patients with gastric cancer. Anemia is a frequent complication of
      gastrectomy. Patients undergoing total or subtotal gastrectomy should be
      carefully monitored for the development of anemia and be given appropriate
      treatment when indicated. This survey-based study aimed to determine the level of
      knowledge about post-gastrectomy anemia in Turkish medical oncologists. METHODS:
      The study included 110 Turkish medical oncologists that agreed voluntarily to
      participate in the survey and answer an 8-item questionnaire. The survey was
      distributed as a questionnaire during the 5th Turkish Medical Oncology Congress
      in March 2014. RESULTS: All participants completed the questionnaire. Most of the
      participants would not recommend oral iron or cobalamin replacement after
      gastrectomy. CONCLUSION: The results of the survey indicate that Turkish medical
      oncologists have some knowledge about post-gastrectomy anemia, but need to learn
      more about appropriate follow-up and replacement therapies for post-gastrectomy
      anemia.

PMID- 26214635
TI  - TNM staging system may be superior to Lugano and Ann Arbor systems in predicting
      the overall survival of patients with primary gastrointestinal lymphoma.
AB  - PURPOSE: To assess the survival predicting value of TNM, Lugano, and Ann Arbor
      staging systems in patients with primary gastrointestinal lymphoma (PGL).
      METHODS: 101 patients with PGL were reviewed. All of them were staged according
      to TNM, Lugano, or Ann Arbor staging system. Five-year survival overall
      survival/OS rate was used as major clinical outcome. The prognostic value of
      different variables like depth of tumor infiltration (T), lymph node status (N),
      metastasis (M), sex, age, LDH, ECOG performance status (PS), subtypes, and tumor
      sites were assessed in relation to clinical outcome. RESULTS: The median follow
      up time was 46.6 months (range 1.3-158.6). The estimated 5-year OS rate was
      74.22%. In gastric lymphoma ,the 5-year OS rate was well correlated with stage in
      the TNM system (stage I 100.00%, stage II 87.18%, stage III 75.17%, and stage IV
      16.67%. p<0.0001), but there were inverse 5-year OS or overlapped survival in the
      Lugano (81.48% in stage II, 85.71% in stage IIE) and Ann Arbor systems (69.47% in
      stage IIE, 66.67% in stage IIIE). In aggressive lymphomas, the 5-year OS of TNM
      stage I, stage II, stage III , and stage IV was 100.00%, 81.34%, 63.52%, and
      16.00%, respectively (p=0.0002), but there were overlapped survival curves in
      Lugano and Ann Arbor systems. The 5-year OS of patients with T1 or T2 was
      significantly superior compared to patients with T3 or T4 (96.15 vs 67.92%,
      p=0.0087), and multivariate Cox analysis showed that T (p=0.0181) and M
      (p=0.0031) were the covariates prognostically significant for OS. CONCLUSION: TNM
      staging system may be superior to Lugano and Ann Arbor system in predicting OS of
      patients with PGL.

PMID- 26214636
TI  - BCL2 positive and BCL6 negative diffuse large B cell lymphoma patients benefit
      from R-CHOP therapy irrespective of germinal and non germinal center B cell like
      subtypes.
AB  - PURPOSE: Despite major advances in the treatment of diffuse large B cell lymphoma
      (DLBCL), approximately one third of the patients progress or die, suggesting the
      existence of additional oncogenic events. The purpose of this study was to
      evaluate the prognostic value of the "Hans classifier", and BCL2 and MYC protein
      expression and gene alterations in DLBCL patients treated with CHOP or R-CHOP
      chemotherapy over a 5-year period. Furthermore, we tried to correlate these
      parameters with the International Prognostic Index (IPI). METHODS: The
      immunohistochemical (IHC) expression of CD10, BCL6, MUM1 and BCL2 on paraffin
      embedded formalin-fixed tumor samples from 103 centroblastic DLBCLs was analyzed.
      IHC expression of MYC and fluorescence in situ hybridization (FISH) for MYC and
      BCL2 gene alterations was performed on 67 samples using the tissue microarray
      (TMA) method. RESULTS: The Hans algorithm was not predictive of survival in both
      therapy groups. No significant difference in BCL2 and MYC alterations or MYC
      protein expression in relation to complete response (CR), event-free survival
      (EFS) and overall survival (OS) was observed in our study. High IPI correlated
      significantly with poor outcome and it was identified as independent prognostic
      factor for OS and EFS (both p=0.000). The 5-year OS was 61% in the R-CHOP
      compared to 38% in the CHOP group (p=0.007). Rituximab significantly improved the
      OS in the BCL2 positive (60 vs 29%, p=0.008), and the BCL6 negative (73 vs 25%,
      p=0.001) cases. CONCLUSION: IPI is an independent prognosticator for DL-BCL
      patients and the addition of rituximab significantly improved survival.
      Furthermore, patients with BCL2+ and BCL6-DLBCL benefited from R-CHOP.

PMID- 26214637
TI  - Association of miR-146a rs2910164 polymorphism with squamous cell carcinoma risk:
      a meta-analysis.
AB  - PURPOSE: Recent evidence suggests that the rs2910164 variant of miR-146a is
      associated with the development of certain types of malignancies. Hence, the aim
      of this study was to investigate the association between this genetic variant and
      the susceptibility of squamous cell carcinoma (SCC). METHODS: We performed a
      systematic search using PubMed, EMBASE, ISI Web of Science, Cochrane Central
      Register of Controlled Trials, ScienceDirect, Wiley Online Library and Chinese
      National Knowledge Infrastructure (CNKI) databases with the last search updated
      on November 15, 2014. Studies were pooled and summary odds ratios (ORs) were
      calculated. Potential sources of heterogeneity were sought out via subgroup
      analysis. RESULTS: A total of 12 studies (5192 cases and 9945 controls) were
      found to be eligible for meta-analysis. Overall, no significant associations were
      found between miR-146a G/C polymorphism and SCC risk when all studies were pooled
      into the meta-analysis. In the subgroup analysis by cancer location,
      statistically significantly increased risks were found for cervical SCC/CSCC (CC
      vs CG+GG:OR = 0.521, 95% CI=0.412-0.657,p<0.001; CC+CG vs GG:OR=1.583,
      95%CI=1.215-2.062,p=0.001); and for skin SCC (GC vs CC+GG:OR=2.533, 95% CI=1.989
      3.224, p<0.001). In addition, the C allele and CC genotype of rs2910164 were
      found to be associated with an inverse risk of nasopharyngeal carcinoma (GG vs
      CC:OR=0.586, 95% CI=0.405-0.847, p=0.005; CC vs CG+GG:OR=1.496, 95% CI=1.189
      1.881, p=0.001). Similarly, CC genotpe of rs2910164 was found to be inversely
      related to susceptibility of oral SCC (CC+CG vs. GG: OR=0.726, 95% CI=0.607
      0.869, p<0.001). CONCLUSIONS: The miR-146a rs2910164 polymorphism is associated
      with increased risk for cervical and skin SCC. In contrast, rs2910164 in miR-146a
      is related to decreased risk for nasopharyngeal and oral SCC.

PMID- 26214638
TI  - Performance indicators collected from primary health centres included in
      organised cervical cancer screening programme in the Republic of Serbia.
AB  - PURPOSE: To present the performance indicators for monitoring the cervical cancer
      screening process conducted in primary health centres (PHCs) and to identify any
      shortcomings in the implementation of the Organized Cervical Cancer Screening
      Programme (OCCSP). METHODS: This study included 16 PHCs participating in the
      OCCSP in the Republic of Serbia. The data were analysed from the moment the
      methodology in the PHCs has been accurately and consistently applied in
      accordance with the European guidelines (earliest from 20th December 2012 until
      30th November 2014). We constructed "the standardised" model (adjusted on the
      number of working months). Performance indicators analysed in this study were:
      coverage by invitation, coverage by examination, and compliance with invitation.
      RESULTS: According to "the standardised" model, coverage by invitation was 61.9%,
      coverage by examination was 35.5% and compliance to invitation was 57.3%.
      CONCLUSION: Social mobilization, education, effective promotion strategies and
      training about cervical cancer screening program-especially in women of target
      population-as well as better coordination and planning of capacity-building, and
      staff resources in PHCs, are needed in the future in order to obtain higher
      values for our performance indicators. Screening registration will provide
      additional information about demographic characteristics of the tested women.

PMID- 26214639
TI  - Does neoadjuvant chemotherapy plus cytoreductive surgery improve survival rates
      in patients with advanced epithelial ovarian cancer compared with cytoreductive
      surgery alone?
AB  - PURPOSE: The purpose of this study was to compare the outcomes of interval
      debulking surgery after neoadjuvant chemotherapy (NAC/IDS) with primary debulking
      surgery (PDS) in patients diagnosed with advanced epithelial ovarian cancer
      (EOC). METHODS: A total of 292 patients with IIIC and IV disease stages, who were
      treated with either NAC/IDS or PDS between 1995 and 2012 were retrospectively
      reviewed. The study population was divided into two groups: the NAC/IDS group
      (N=84) and the PDS group (N=208). Progression-free survival (PFS), overall
      survival (OS), and optimal cytoreduction were compared. RESULTS: The mean patient
      age was significantly higher in the NAC/IDS group (61.5+/-11.5 vs 57.8+/-11.1,
      p=0.01). Optimal cytoreduction was achieved in 34.5% (29/84) of the patients in
      the NAC/IDS group and in 32.2% (69/208) in the PDS group (p=0.825). The survival
      rates were comparable. The survival rate of patients who received optimal
      cytoreductive surgery in either the PDS or the NAC/IDS arm was significantly
      higher than that of patients who received suboptimal cytoreductive surgery
      (p<0.01 and p<0.01, respectively). Multivariate analysis confirmed the treatment
      method, amount of ascitic fluid, and optimal cytoreduction as independent factors
      for OS. CONCLUSIONS: There was no definitive evidence regarding whether NAC/IDS
      increases survival rates compared with PDS. NAC should be reserved for patients
      who cannot tolerate PDS or when optimal cytoreduction is not feasible.

PMID- 26214640
TI  - Kallikrein expression as a prognostic factor in ovarian cancer: a systematic
      review and meta-analysis.
AB  - PURPOSE: Kallikrein is considered as a mediator of tumorigenesis. Various studies
      examing the relationship between high kallikrein expressions with the clinical
      outcome in patients with ovarian cancer have yielded controversial conclusions.
      METHODS: We conducted a meta-analysis of 10 studies (N=1478) that evaluated the
      relationship between positive kallikrein expression and overall survival and
      progression-free survival (PFS). Data were analyzed with random effect and
      combined hazard ratios (HR) by STATA software. RESULTS: Positive kallikrein
      expression was significantly associated with worse OS (HR for OS was 2.01, 95%CI:
      1.68-2.34, p<0.05). Subgroup analysis showed that kallikrein detected by RT-PCR
      was related with OS (HR=2.51, 95%CI: 2.16-2.86, p<0.05), as well as by nonY-PCR
      methods (HR=1.6, 95%CI: 1.08-2.12, p<0.05). The heterogeneity among studies was
      significant (I2-91%, p=0.000). Begg's and Egger's test showed p=0.813 and
      p=0.938, respectively. The estimated HR for PFS was 1.83, 95%CI: 1.51-2.14,
      p<0.05). The heterogeneity among studies was significant (I2=88.9%, p=0.000).
      Begg's and Egger's test showed p=0.93 and p=0.88, respectively. Furthermore,
      confunnel plot (contour-enhanced funnel plot) was undertaken which also showed
      absence of publication bias for both OS and PFS. CONCLUSION: Although the
      presence of some modest bias cannot be avoided, positive kallikrein expression
      seems to be associated with worse OS and PFS in patients with ovarian cancer.

PMID- 26214641
TI  - Utilization of ultrasound as a diagnostic tool in the preoperative assessment of
      patients with adnexal masses.
AB  - PURPOSE: To evaluate the reliability of ultrasound scan (US) findings in the
      preoperative assessment of the nature of adnexal masses in females. METHODS:
      After detailed history, a preoperative US examination was performed in all women.
      Tumor diameter, localization, the presence of solid, cystic and multilocular
      components, excrescences, metastasis and free fluid were assessed. Doppler scan
      was done and pulsatility (PI) and resistance indices (RI) were determined. These
      data were compared with postoperatively obtained histopathological findings and
      statistically analyzed. RESULTS: The study included 609 women out of which 20.7%
      had malignant, 73.7% benign, and 5.6% border-line tumors. Patients with malignant
      tumors were oldest (p<0.001). There were significantly more positive US
      parameters in malignant than in benign tumors (p<0.001). Also, there were
      significant differences (p<0.001) between malignant, benign and borderline tumors
      regarding all examined US and Doppler parameters except tumor multilocularity. RI
      had sensitivity 75%, specificity 61.2%, positive predictive value (PPV) 42.70%
      and negative predictive value (NPV) 96.16%. PI had sensitivity 50%, specificity
      35.3%, PPV 8.37% and NPV 25.93%. Sensitivity of US characteristics was 94.34%,
      specificity 30.62%, PPV 22.27% and NPV 96.25%. CONCLUSIONS: US pattern
      characteristics and Doppler parameters were found to be moderately reliable in
      discriminating malignant, benign and borderline adnexal tumors. Tumor of solid or
      mixed consistency, presence of ascites and excrescences were the best predictors
      of malignancy.

PMID- 26214642
TI  - Prognostic value of vascular endothelial growth factor expression in women with
      ovarian cancer: A meta-analysis.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is a signal protein which is
      responsible for angiogenesis through promoting migration and mitosis of
      endothelial cells. The aim of our study was to investigate the existing evidence
      about whether VEGF is associated with prognosis of ovarian cancer. METHODS: We
      conducted a meta-analysis of 19 studies (n=1352 patients) that focused on the
      correlation of VEGF expression with overall survival (OS), disease-free survival
      (DFS) and progression-free survival (PFS). Data were synthesized with random or
      fixed effect hazard ratios (HR). The studies were categorized by author/year,
      number of patients, FIGO stage, histology, cutoff value for VEGF positivity,
      methods of detection, types of survival analysis, methods of HR estimation, and
      HR and their 95% confidence interval (CI). RESULTS: Combined HR suggested that
      VEGF positivity was associated with poor OS, but not with DFS and PFS. The HR and
      95% CI were: HR=1.66, 1.22-2.00 in OS; 1.85, 0.56-3.15 in DFS; and 1.23, 0.62
      1.84 in PFS. Subgroup analysis showed that VEGF was irrelevant with OS in
      specimens from tissues (HR=1.32, 95% CI: 0.82-1.82) with 95% CI overlapping 1,
      but could indicate poor prognosis in specimens from serum (HR=2.07, 95% CI: 1.45
      2.70) CONCLUSION: The OS of the VEGF-positive group with ovarian cancer was
      significantly poorer than the VEGF-negative group. However, VEGF positivity seems
      not to be connected with DFS and PFS.

PMID- 26214643
TI  - Supracricoid partial laryngectomy: oncological and functional results.
AB  - PURPOSE: The purpose of this study was to evaluate the oncological and functional
      results of patients affected by laryngeal squamous cell carcinoma (SCC) and
      surgically treated by supracricoid partial laryngectomy (SCPL) at the ENT
      Department of the University Hospital of Ferrara. METHODS: In this retrospective
      study a total of 155 patients (149 males/l96.1% and 6 females/3.9%), have been
      included. All patients were treated between January 1st 1998 and December 31st
      2010, by SCPL, including 126 cricohyoidopexies (CHP) and 29
      cricohyoidoepiglottopexies (CHEP). RESULTS: The overall survival (OS) at 3 and 5
      years was 88.77 and 83.24%, respectively and the disease-free survival (DFS) at 3
      and 5 years was 84.4 and 81.55%, respectively.The recurrence rate was 17.5%, with
      local recurrences in 12.1% of the cases, regional in 4.7% and distant metastasis
      in 0.7% of the cases. Synchronous second primary tumors were 0.7% and
      metachronous second primary cancers (MSPCs) 5.4%. Removal of nasogastric feeding
      tube (NGT) or percutaneous endoscopic gastrostomy (PEG) was performed in 98.7% of
      the patients and lasted 22 days on average after SCPL (range 9-60), while
      decannulation was performed in all of patients at the 27th day on average after
      surgery. CONCLUSIONS: Oncological outcomes of this series are consistent with
      those of the literature, showing that SCPL is an effective and safe procedure in
      terms of survival rate and disease control. Functional outcomes confirmed that
      SCPL allows a good organ preservation and recovery of laryngeal functions.

PMID- 26214644
TI  - Effect on long-term survival of psychiatric disorder, inflammation, malnutrition,
      and radiotherapy-related toxicity in patients with locally advanced head and neck
      cancer.
AB  - PURPOSE: To evaluate the effects on the long-term survival of psychiatric
      disorders, inflammation, malnutrition, and radiotherapy (RT)-related toxicity in
      patients with locally advanced head and neck cancer. METHODS: Included were 47
      patients who received RT for non-metastatic locally advanced head and neck
      cancer. The diagnosis of psychiatric disorder was made by the Diagnostic and
      Statistical Manual of Mental disorders (4th edn) (DSM-IV) criteria. Malnutrition
      was defined as weight loss >5% of baseline during RT. Interleukin 1beta (IL
      1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were analyzed by enzyme
      linked immunosorbent assay (ELISA). RT-related acute toxicity was evaluated once
      a week using the National Cancer Institute Common Toxicity Criteria (NCI-CTC)
      version 2.0. RESULTS: The mean patient age was 57.3+/-11.4 years (range 33-80);
      42 (89.4%) patients were male. Mean disease-free (DFS) and overall survival (OS)
      were 53 and 55 months, respectively. Mean DFS was significantly lower in patients
      with psychiatric disorder compared with those without (35 vs 59 months, p=0.013)
      and the same applied for mean OS (41 vs 61 months, p=0.008). There was no
      significant difference between patients with and without malnutrition in terms of
      OS. Similarly, no significant difference was seen between patients with and
      without RT-related toxicities in terms of OS. Age, psychiatric disorder, T
      status, and stage differed significantly between these groups (p<0.10) in
      univariate analysis. The multivariate Cox regression analysis identified that the
      OS was significantly associated only with psychiatric disorder (odds ratio/OR:
      3.22, 95% confidence interval/CI: 1.29-8.41, p=0.013). CONCLUSION: Psychiatric
      disorders had unfavorable effects on OS in patients with locally advanced head
      and neck cancer. Inflammation, malnutrition and RT-related toxicity had no
      significant impact on OS.

PMID- 26214645
TI  - Gefitinib causes growth arrest and inhibition of metastasis in human
      chondrosarcoma cells.
AB  - PURPOSE: Chondrosarcomas are primary malignant cartilage-forming tumors of bone
      which are not responsive either to chemotherapy or radiation treatment and
      display potent capacity to invade locally and cause distant metastasis. Epidermal
      growth factor receptor (EGFR) pathway plays an important role in the development
      and progression of many cancers. However, the effect of EGFR inhibitor gefitinib
      on cell growth and metastasis in human chondrosarcoma cells is largely unknown.
      METHODS: Features of the protein expression of EGFR in 3 human chondrosarcoma
      cell lines JJ2012, SW1353 and OUMS27 were analyzed. The inhibitory effects of
      EGFR inhibitor gefitinib on cell proliferation, cell cycle and metastasis were
      assessed by using MTS, flow cytometry and migration assays, respectively. The
      expression of metastasis-related proteins was evaluated by western blotting.
      RESULTS: All the three human chondrosarcoma cell lines expressed EGFR protein.
      Gefitinib significantly inhibited the growth, induced cell cycle arrest and
      decreased the migra- tion ability of human chondrosarcoma cells. In addition,
      gefitinib also reduced the expression of metastasis-related proteins, basic
      fibroblast growth factor (bFGF), matrix metalloproteinases-2 (MMP-2) and matrix
      metalloproteinases-9 (MMP-9). CONCLUSIONS: The discovery that gefitinib inhibited
      the proliferation and reduced the metastatic capacity of chondrosarcoma cells may
      help increase the understanding of the mechanism underlying human chondrosarcoma
      growth and metastasis. Thus, gefitinib may represent a promising agent for
      controlling chondrosarcoma proliferation and metastasis.

PMID- 26214646
TI  - Increased cancer risk associated with the -607C/A polymorphism in interleukin-18
      gene promoter: an updated meta-analysis including 12,502 subjects.
AB  - PURPOSE: Increasing investigations have been performed on the association of 
      607C/A polymorphism in Interleukin-18 (IL-18) gene promoter with cancer risk and
      have yielded conflicting results. To derive a more precise estimation of the
      association, we performed an updated meta-analysis of all eligible studies.
      METHODS: We searched all eligible studies by using PubMed, MEDLINE, EMBASE, and
      China National Knowledge Infrastructure (CNKI) databases. The odds ratios (ORs)
      were pooled by the fixed-effects/random-effects model in STATA 12.0 software.
      RESULTS: This meta-analysis included 29 studies with 6,026 cases and 6,476
      controls. Overall, significantly increased cancer risk was observed (A vs C:
      OR=1.10, 95% CI: 1.01,1.19, Pheterogeneity=0.001; AA vs CC: OR=1.17, 95% CI:
      1.01,1.37, Pheterogeneity=0.007; CA vs CC: OR=1.15, 95% CI: 1.05,1.25,
      Pheterogeneity=0.152; AA/CA vs CC: OR=1.17, 95% CI: 1.06,1.31,
      Pheterogeneity=0.042). In subgroup analyses based on ethnicity, the results
      suggested a significantly increased risk of cancer in Asian population (CA vs CC:
      OR=1.11, 95% CI: 1.00-1.24, Pheterogeneity=0.353; AA/CA vs CC: OR=1.14, 95% CI:
      1.02-1.29, Pheterogeneity=0.081) and in Mixed population (A vs C: OR=1.72, 95%
      CI: 1.22-2.43, Pheterogeneity=NA; AA vs CC: OR=2.84, 95% CI: 1.43-5.64,
      Pheterogeneity=NA; AA vs CC/CA: OR=2.43, 95% CI: 1.34-4.42, Pheterogeneity=NA;
      AA/CA vs CC: OR=1.69, 95% CI: 1.00-2.85, Pheterogeneity=NA); however, no
      significant association was found in Caucasian or African populations. In the
      subgroup analysis by cancer type we found a significantly increased
      susceptibility to breast cancer (A vs C: OR=1.33, 95% CI: 1.00
      1.75,Pheterogeneity=0.155; AA vs CC: OR=1.80, 95% CI: 1.02
      3.21,Pheterogeneity=0.162; AA7sol;CA vs CC: OR=1.33, 95% CI: 1.00
      1.78,Pheterogeneity=0.546), nasopharyngeal carcinoma (A vs C: OR=1.16, 95% CI:
      1.01-1.32, Pheterogeneity=0.921; AA vs CC: OR=1.34, 95% CI: 1.02-1.75,
      Pheterogeneity=0.863; CA vs. CC: OR=1.36, 95% CI: 1.08-1.70,
      Pheterogeneity=0.824; AA/CA vs CC: OR=1.35, 95% CI: 1.09
      1.68,Pheterogeneity=0.904), and esophageal cancer (CA vs CC: OR=1.37, 95% CI:
      1.04-1.80, Pheterogeneity=0.528; AA/CA vs CC: OR =1.29, 95% CI: 1.00-1.66,
      Pheterogeneity=0.700). CONCLUSIONS: The current meta-analysis suggests that the 
      607C/A polymorphism in IL-18 gene promoter is associated with a significantly
      increased risk of cancer, especially of breast cancer, nasopharyngeal carcinoma
      and esophageal cancer and in Asian and Mixed populations. More studies with
      diverse ethnic groups, larger sample size, and well controlled confounding
      factors are warranted to further investigate the association.

PMID- 26214648
TI  - Feasibility of rapid infusion of the initial dose of bevacizumab in patients with
      cancer.
AB  - PURPOSE: Bevacizumab is a monoclonal antibody against vascular endothelial growth
      factor (VEGF) widely used in clinical oncology. Bevacizumab is commonly co
      adminis- tered with chemotherapy. It is recommended that the first infusion of
      the antibody last 90 min, the second 60 and all subsequent 30 min. Since there is
      no clear rationale for the proposed schedule of administration, our study
      assessed the feasibility of a 30 min initial infusion. METHODS: Cancer patients
      eligible for de novo bevacizumab treatment were enrolled. All patients received
      standard bevacizumab dose of 5, 7.5 or 10 mg/kg according to the indication,
      diluted in 250 ml normal saline, as a 30-min intravenous infusion. RESULTS:
      Thirty two patients were enrolled: male 18, female 14, median age 58 years, range
      42-78. Oncologic diagnosis: lung cancer 16, colorectal 4, breast 3, ovarian 7,
      renal 2. All patients tolerated the infusion well. No hypersensitivity reactions
      were noted. Mean systolic and diastolic blood pressures were 122 and 73 mm/Hg
      respectively prior to the infusion and 125 and 75 mm/Hg 15 min after the infusion
      (p=0.3). During the observation period of 1 hour, blood pressure did not change.
      Transient grade 3 systolic hypertension was noted in 1 patient, with spontaneous
      regression in 45 min. CONCLUSION: Rapid administration of bevacizumab in 30 min,
      rather than the recommended in the package insert 90 min is feasible and safe.
      Such a practice limits the time of confinement in the treatment area to patients'
      satisfaction and would result in cost savings by reducing health resource
      utilization.

PMID- 26214647
TI  - A meta-analysis of MTRR A66G polymorphism and colorectal cancer susceptibility.
AB  - PURPOSE: A meta-analysis was performed to determine the association between MTRR
      A66G polymorphism and colorectal cancer (CRC) susceptibility. METHODS: Based on
      comprehensive searches of the MEDLINE, EMBASE and ISI Web of knowledge, China
      National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified
      eligible studies about the association between MTRR A66G polymorphism and CRC
      susceptibility. RESULTS: A total of 6020 cases and 8317 controls in 15 studies
      were pooled together for evaluation of the overall association between MTRR A66G
      polymorphism and susceptibility of CRC. The allele model (G vs A: p=0.01;
      OR=1.07, 95% CI=1.02-1.12), and homozygous model (GG vs AA: p=0.006; OR=1.15, 95%
      CI=1.04-1.28) showed increased risk for CRC development. Similarly, the dominant
      model (GG+GA vs AA: p=0.04; OR=1.11, 95% CI=1.01-1.22) and the recessive model
      (GG vs GA+AA: p=0.04; OR=1.08, 95% CI=1.00-1.17) showed increased risk for CRC
      development. In the analysis stratified by ethnicity (Caucasian and East Asian),
      significant associations were found between MTRR A66G polymorphism and
      susceptibility to CRC among Caucasians. CONCLUSION: Our pooled data suggest an
      association between MTRR A66G polymorphism and CRC susceptibility among
      Caucasians.

PMID- 26214649
TI  - Bleomycin-induced pneumonitis in three patients treated with chemotherapy for
      primary advanced seminoma.
AB  - PURPOSE: Bleomycin, etoposide and cisplatinum (BEP) comprise the most common
      regimen in the treatment of advanced testicular tumors, including seminoma.
      Common side effects are of hematologic, renal, and cardiovascular origin. One of
      the most prominent side effects is pulmonary toxicity attributed to bleomycin. We
      describe three patients who developed bleomycin-induced pneumonitis (BIP) with
      full recovery. METHODS: Pre-and post-treatment clinical, biochemical (including
      specific tumor markers) and radiological response assessment of 26 patients with
      primary advanced seminoma (AS) who were referred to our hospital for platinum
      based chemotherapy between 1989-2010 are described. RESULTS: All patients were
      assessable for evaluation and all achieved long-term complete remission. Side
      effects were mild and manageable. Three patients developed bleomycin pulmonary
      toxicity after reaching cumulative doses of 180-240 units. All three patients
      presented with classical symptoms of non-productive cough, exertional dyspnea,
      and low-grade fever. Radiologically, the patients presented in the first months
      following completion of chemotherapy with initial bilateral interstitial and
      alveolar infiltrates, which worsened and progressed into consolidation and then
      regressed until total disappearance. All patients were treated with high-dose
      steroids and broad-spectrum antibiotics. CONCLUSION: AS is a very chemotherapy
      responsive and sensitive disease, and approximately 90% of the patients enjoy
      complete regression of tumor masses and durable and sustained long-term survival
      with no evidence of disease. BIP may be a dangerous acute and chronic side
      effect, even in doses lower than 360 units. Considering the favorable clinical
      outcome of our patients, prompt diagnosis should be made and rapid medical
      intervention should be implemented.

PMID- 26214650
TI  - Colonic polyp harboring lung cancer metastasis: An unpleasant surprise.

PMID- 26214651
TI  - Peri-operative maintenance of dual antiplatelet therapy is safe in patients
      requiring laser cordectomy for laryngeal cancer.

PMID- 26214652
TI  - Can aromatase inhibitors cause forgetfulness in women with breast cancer ?

PMID- 26214653
TI  - Electromagnetic machines in cancer treatment: The "Priore affair".
AB  - In the 1960s and 1970s the Italian born scientist Antonio Priore, working in
      France, amazed the public and divided the scientific world with his invention, a
      machine which could cure a variety of illnesses, including cancer. Gaining the
      support of the French government and several scientific organizations, Priore
      received a great amount of money in funds to sustain his research. Without
      exposing his exact method, the scientific world questioned the legitimacy of
      Priore's research. For almost two decades scientists, institutes, journalists and
      cancer patients were implicated in a sensational case, known as the "Priore
      affair". 

PMID- 26214654
TI  - Thin films of size-selected Mo clusters: growth modes and structures.
AB  - Thin films of MoO3 were prepared by deposition of size-selected ligand-free Mo
      clusters under high vacuum conditions and subsequent exposure to air. The growth
      pattern is highly dependent on the cluster size. At low coverage, small clusters
      (Mo51) form a continuous monolayer of fused particles. On top of this monolayer,
      additional clusters survive as individual entities. Medium sized clusters (Mo251
      and Mo1253) do not coalesce and form a monolayer of clusters. Close examination
      using in situ scanning tunneling microscopy reveals a local order of the
      particles. At higher coverage a new pattern of large 3-dimensional aggregations
      of clusters (pylons) appears. The pylons are not formed under high vacuum
      conditions. Their formation is most likely caused by the air exposure. For the
      largest clusters (Mo3349) studied here, no monolayer is formed. Instead, the
      clusters are randomly distributed as expected for particles with zero mobility.
      These results demonstrate the high potential of cluster deposition for the
      production of new types of nanostructured surfaces, thin films and nanomaterials.

PMID- 26214655
TI  - Click-In Ferroelectric Nanoparticles for Dielectric Energy Storage.
AB  - Polymer-ceramic nanocomposites have been thoroughly investigated previously for
      high energy storage devices. However, the increase in performance of these
      nanocomposites has proven to be significantly lower than predicted values.
      Through surface functionalization of high dielectric constant nanoparticles (NP),
      the flaws that reduce composite performance can be eliminated to form high energy
      density composite materials. Functionalization methods utilize high throughput
      printing and curing techniques (i.e., inkjet printing and xenon flash lamp
      curing) that are crucial for rapid adoption into industrial production. (Ba,Ca)
      (Zr,Ti)O3 NPs (50 nm) are synthesized through the solvothermal method and
      functionalized with alkene terminated methoxysilanes. A thiol-ene monomer ink
      system, PTD3 [pentaerythritol tetrakis (3-mercaptopropionate) (PEMP, P), 1,3
      Diisopropenylbenzene (DPB, D), 2,4,6-Triallyloxy-1,3,5-triazine (TOTZ, T)], is
      used as a high breakdown polymer matrix. Neat polymer, alkene terminated NP
      polymer composites, and hydrophilic, TBAOH functionalized NP-polymer composites
      were spin coated onto both copper laminated glass slides and printed onto copper
      substrates in 1 cm(2) patterns for testing. Alkene functionalized NPs increased
      the breakdown strength by ~38% compared to the nonfunctionalized NPs.
      Functionalized NPs increased both the breakdown strength and dielectric constant
      compared to the neat polymer, increasing the energy density nearly 3-fold from
      13.3 to 36.1 J.cm(-3). 

PMID- 26214656
TI  - Posaconazole for primary antifungal prophylaxis in patients with acute myeloid
      leukaemia or myelodysplastic syndrome during remission induction chemotherapy: a
      single-centre retrospective study in Korea and clinical considerations.
AB  - Posaconazole was introduced as the primary antifungal prophylaxis (PAP) in acute
      myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) patients during
      remission induction chemotherapy. Data on breakthrough invasive fungal infections
      (IFIs) from various centres are essential, as there are several considerations in
      treating IFIs in the posaconazole era. The aim of this study was to evaluate the
      effectiveness of posaconazole PAP and identify characteristics of IFIs at a
      single centre in Korea. We retrospectively reviewed consecutive patients with
      AML/MDS undergoing remission induction chemotherapy between December 2010 and
      November 2013. Of the 424 patients, 140 received posaconazole and 284 received
      fluconazole prophylaxis. The incidence of breakthrough proven/probable IFIs
      (15.5% vs. 2.9%, P < 0.001) and empirical antifungal treatment (EAFT) (45.8% vs.
      12.9%, P < 0.001) decreased in the posaconazole group compared to the fluconazole
      group. In the posaconazole PAP group, two cases of breakthrough mucormycosis were
      noted among 13 proven/probable/possible IFI cases (15.4%). Overall and IFI
      related mortality was 12.1% and 1.9% respectively. Fungus-free survival was
      significantly higher in the posaconazole group (74.7% vs. 87.1%, P = 0.028).
      Breakthrough IFIs and EAFT decreased significantly after posaconazole PAP. The
      benefit in fungus-free survival was noted with posaconazole PAP. Clinicians
      should be vigilant to identify non-Aspergillus IFIs with active diagnostic
      effort.

PMID- 26214657
TI  - Pulsed light induced damages in Listeria innocua and Escherichia coli.
AB  - AIMS: Pulsed light (PL) is an upcoming nonthermal decontamination technology
      mainly used for surface sterilization. The objective of this study was to
      investigate the extent of cellular damage caused by PL treatments of Listeria
      innocua and Escherichia coli on a polysaccharide surface in order to gain
      knowledge about the main inactivation pathways. METHODS AND RESULTS: The impact
      of PL on the cellular ATP level was investigated as well as the bacterial ability
      to take up fluorescently labelled glucose (2-NBDG). Furthermore, the extent of
      DNA damages was assessed by qPCR. The ability of L. innocua and E. coli to
      photorepair under artificial daylight exposure was quantified. Finally, the
      induction of reactive oxygen species (ROS) and lipid peroxidation were studied by
      fluorometric detection of ROS and thiobarbituric acid reactive substances
      (TBARS). It is shown that intracellular ATP levels and glucose uptake ability do
      not correlate with the immediate loss of bacterial reproducibility, which
      indicates that cellular activity and energy may remain on a relatively high
      level, although growth on tryptic soy agar is not observable. Sequence specific
      investigation of PL induced DNA damages by qPCR revealed distinct differences
      between L. innocua and E. coli although the observed inactivation efficacy of PL
      by the culture based method was similar. Photoreactivation has been observed for
      both bacteria, a higher recovery rate of up to 2 log was seen in case of E. coli.
      Intracellular ROS and lipid peroxides were both detectable at relatively high
      fluencies with E. coli so the contribution of oxidative damage to microbial
      inactivation of PL cannot be excluded. CONCLUSIONS: Escherichia coli as well as
      L. innocua cells have proven to maintain residual cellular activity after having
      been exposed to PL even when they are not able to reproduce any more. High
      proportions of sublethal damages were also obvious with regard to occurring
      photoreactivation. The destruction of bacterial DNA seems to be the primary
      mechanism of inactivation of PL but the involvement of other factors like
      oxidative stress cannot be excluded. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      observed data underline that bacteria are not immediately inactivated after
      exposure to PL as different indicators of cellular energy are still detectable
      even when cells do not reproduce on solid media any more. DNA is the primary
      target of PL, but as the extent of damage among different bacteria may not reveal
      their actual sensitivity, other destructive effects should also be considered.

PMID- 26214658
TI  - Facile synthesis of multiple enzyme-containing metal-organic frameworks in a
      biomolecule-friendly environment.
AB  - The one-step and facile synthesis of multi-enzyme-containing metal-organic
      framework (MOF) nanocrystals in aqueous solution at 25  degrees C was reported in
      this study. The GOx&HRP/ZIF-8 nanocomposite displayed high catalytic efficiency,
      high selectivity and enhanced stability due to the protecting effect of the
      framework. 

PMID- 26214660
TI  - Intact information sampling in mesial temporal lobe epilepsy.
AB  - OBJECTIVE: Previous studies have reported deficits in decision making under
      ambiguity for patients with mesial temporal lobe epilepsy (mTLE). It is unknown
      whether mTLE is also associated with alterations at a predecisional stage. This
      study aimed to gain insight into predecisional processing of patients with mTLE.
      METHOD: We compared performance of patients with mTLE (n = 25) with that of
      healthy controls (n = 75) on the information sampling task (IST), a task
      assessing reflection-impulsivity and predecisional information sampling. RESULTS:
      Patients and healthy controls showed a similar performance pattern in both
      conditions of the IST as indicated by the amount of information gathered, the
      degree of uncertainty tolerated, and the number of decision errors made. They
      both also demonstrated a significant sensitivity to the different reward
      characteristics of the task. For the patient group, we found no significant
      effects on performance on the IST of epilepsy lateralization, abnormality side,
      structural abnormality (hippocampus vs. amygdala), and medication (monotherapy
      vs. polytherapy). CONCLUSIONS: Reflection processes and predecisional information
      sampling as tested by the IST are intact in mTLE. Patients collect as much
      information as healthy individuals and adapt their behavior according to the
      changing reward conditions. Our findings indicate that in well-defined risk
      situations, where memory demands are sufficiently minimized, patients with mTLE
      should be able to gather sufficient information, weight risks and benefits, and
      make advantageous decisions.

PMID- 26214659
TI  - Does processing speed mediate the effect of pediatric traumatic brain injury on
      working memory?
AB  - OBJECTIVE: Processing speed (PS) and working memory (WM), core abilities that
      support learning, are vulnerable to disruption following traumatic brain injury
      (TBI). Developmental increases in WM are related to age-related changes in PS.
      The purpose of this study was to investigate whether WM deficits in children with
      TBI are mediated by PS. METHOD: The performance of children with complicated
      mild, moderate, and severe TBI (n = 77) was examined relative to an orthopedic
      injury (n = 30) and a healthy comparison group (n = 40) an average of 4 years
      after injury (range 8 months to 12 years). Coding was utilized as a measure of
      PS, while the WM measures included complex verbal and visual-spatial span tasks
      with parallel processing requirements. Mediation analysis examined whether TBI
      might have an indirect effect on WM through PS. RESULTS: Children in the TBI
      group performed more poorly than the combined comparison groups on coding and
      visual-spatial WM. Verbal WM scores were lower in TBI and the healthy comparison
      relative to the orthopedic group. TBI severity group differences were found on
      coding, but not WM measures. The relation between coding and both the WM tasks
      was similar. Bootstrap regression analyses suggested that PS, as measured by
      coding, might partially mediate the effect of group performance on WM.
      CONCLUSIONS: TBI disrupts core PS and WM abilities that scaffold more complex
      abilities. Importantly, slowed PS was associated with WM deficits commonly
      identified following pediatric TBI. Implications of our findings regarding the
      relation between PS and WM may suggest interventions for children and adolescents
      following TBI.

PMID- 26214661
TI  - On the appropriateness of norm- and criterion-referenced assessments in medical
      education.

PMID- 26214662
TI  - Erratum.
AB  - In Ear Nose Throat J 2015;94(4-5):150-2, an editing error was made in the title.
      The correct title is "Perineural spread of cutaneous squamous cell carcinoma
      along the great auricular nerve."

PMID- 26214663
TI  - Intratympanic membrane congenital cholesteatoma.

PMID- 26214664
TI  - Diplopia: An uncommon presentation of silent sinus syndrome.

PMID- 26214665
TI  - Salivary gland adenoid cystic carcinoma.

PMID- 26214666
TI  - Fetal rhabdomyoma of the tongue in a newborn.

PMID- 26214667
TI  - A rare case of malignant fibrous histiocytoma (pleomorphic undifferentiated
      sarcoma NOS) of the vocal fold.
AB  - Malignant fibrous histiocytoma, also known as pleomorphic undifferentiated
      sarcoma not otherwise specified, arises in numerous organs. The first-line
      treatment is complete excision of the mass, but in some cases postoperative chemo
      and/or radiotherapy is recommended. Only a few cases of malignant fibrous
      histiocytoma of the vocal fold have been previously reported in the literature.
      We report a new case, which originated in the true vocal fold of a 65-year-old
      man. The mass was removed via CO2 laser excision with preservation of the vocal
      fold and without the need for further treatment. At 3 years of follow-up, the
      patient remained recurrence-free. 

PMID- 26214668
TI  - Anthracosis: An unusual cause of vocal fold paralysis.
AB  - Anthracotic pigmentation in the bronchial mucosa is a bronchoscopic finding of
      pneumoconiosis, or evidence of heavy atmospheric soot. This pigmentation in the
      tracheobronchial mucosa is surrounded by calcified or noncalcified lymph nodes.
      Anthracosis is not a previously known cause of left vocal fold paralysis. We
      present what we believe to be the first reported case of anthracosis-caused vocal
      fold paralysis. 

PMID- 26214669
TI  - Post-thyroidectomy hypocalcemia: Impact on length of stay.
AB  - Hypocalcemia is a recognized complication following thyroid surgery. Variability
      in the definition of hypocalcemia and different opinions on its management can
      lead to unnecessary patient morbidity and longer hospital stays as a result of
      inappropriate or untimely treatment. Therefore, we developed a management
      guideline for the recognition and treatment of post-thyroidectomy hypocalcemia,
      and we conducted a retrospective study to assess its impact on length of stay
      (LOS). Between April 1, 2007, and March 31, 2009, 29 adults had undergone a total
      or completion thyroidectomy at our large district general hospital. Of this
      group, postoperative hypocalcemia (defined as a serum calcium level of <2.00
      mmol/L) developed in 13 patients (44.8%) during the first 3 postoperative days.
      Our guideline went into effect on July 1, 2009, and from that date through June
      30, 2010, 18 more adults had undergone a total or completion thyroidectomy. Of
      that group, hypocalcemia developed in 7 patients (38.9%); the guideline was
      actually followed in 5 of these 7 cases (71.4%). In the preguideline group, the
      development of hypocalcemia increased the mean LOS from 2.0 days to 7.0 days (p <
      0.001). The management of postoperative hypocalcemia in these cases was highly
      variable and was dictated by variations in practice rather than patient needs. In
      the postguideline group, postoperative hypocalcemia increased the mean LOS from
      2.7 days to only 3.7 days (p = 0.07). While the difference between LOS in the two
      hypocalcemic groups did not reach statistical significance, we believe it merely
      reflects the relatively small number of patients rather than any lack of
      guideline efficacy. The implementation of a simple flowchart guideline for the
      management of postoperative hypocalcemia in our hospital has resulted in more
      uniform management and a reduced LOS. 

PMID- 26214670
TI  - Sweet syndrome: A case report and review of the literature.
AB  - Sweet syndrome (acute febrile neutrophilic dermatosis) is a disorder of unknown
      etiology. It has been associated with autoimmune processes, malignancies,
      infections, drug reactions, and gastrointestinal disorders such as inflammatory
      bowel disease. We describe the case of a 51-year-old man who presented with
      severe pain in his tongue and throat and referred pain in his right ear, along
      with odynophagia, fever, and hoarseness of 48 hours'duration. An oral and
      oropharyngeal examination revealed the presence of aphthous ulcerations, as well
      as a 3 * 3-cm raised inflammatory lesion on the right anterior lateral tongue and
      a 5 * 5-mm bulla on the hard palate in the midline. In addition, erythematous
      papules and macules were noted on his face, neck, and extremities. Cultures, a
      biopsy, and laboratory tests yielded a diagnosis of Sweet syndrome. The patient
      was prescribed oral prednisone, and his signs and symptoms resolved within 2
      months. Although Sweet syndrome is uncommon, even in dermatology practice, its
      head and neck and oral manifestations and its association with paraneoplastic
      disease warrant the need for otolaryngologists to be aware of the condition. 

PMID- 26214671
TI  - Maxillary sinus angiomyolipoma: A case report and overview.
AB  - Otolaryngologists are called upon to evaluate and treat sinonasal masses
      discovered incidentally on imaging studies. Although common conditions such as
      sinonasal polyps and mucus retention cysts predominate, it is prudent practice to
      formulate a differential diagnosis to identify unusual conditions. We present a
      case of a maxillary sinus mass in a 78-year-old man that was discovered
      incidentally on brain imaging and subsequently identified on biopsy as an
      angiomyolipoma (AML). AMLs are benign hamartomatous tumors that rarely occur in
      extrarenal locations. Only a few cases have been reported in the nasal cavity. We
      believe our case represents the first reported instance of AML arising within a
      maxillary sinus. Identification of intratumoral fat within the mass on imaging
      studies may suggest the diagnosis of AML preoperatively. Close interdisciplinary
      collaboration among the otorhinolaryngology, radiology, and pathology services is
      beneficial for patient management. We report this case to raise awareness that
      AML can arise in this previously unreported location. Moreover, we wish to
      emphasize that AML should be considered in the differential diagnosis when
      imaging studies demonstrate a well-defined, heterogeneous, fat-containing
      solitary mass in the nasal cavity or maxillary sinus. 

PMID- 26214672
TI  - Oncocytic mucoepidermoid carcinoma of the parotid gland: A case report and review
      of the literature.
AB  - Oncocytic metaplasia rarely has been reported in mucoepidermoid carcinomas. Most
      salivary gland lesions with oncocytic change are benign; therefore, it is
      important to distinguish mucoepidermoid carcinoma from other entities that may
      show prominent oncocytic change. We report a rare case of oncocytic
      mucoepidermoid carcinoma in a 65-year-old woman. 

PMID- 26214673
TI  - Primary melanoma of the petrous temporal bone.
AB  - Melanoma is a malignant tumor of melanocytes that is predominantly found in the
      skin. In rare cases, it arises from mucosal melanocytes. We describe a case of a
      solitary melanoma of the petrous apex of the temporal bone in a 67-year-old woman
      who presented with sudden hearing loss, aural fullness, and headaches, all on the
      right side. Magnetic resonance imaging identified a mass located at the right
      petrous apex; the lesion was hyperintense on T1-weighted imaging and isointense
      on T2 weighting, and it enhanced brightly with gadolinium contrast. The patient
      underwent removal of the lesion via a transcochlear approach with facial nerve
      translocation. Intra- and postoperative pathology identified a poorly
      differentiated malignancy consistent with a melanoma. Further investigations
      found no evidence of metastasis. Given a concern for residual disease, the
      patient was treated with radiation to the primary site. To the best of our
      knowledge, only 1 other case of primary melanoma of the petrous apex has been
      described in the literature. 

PMID- 26214674
TI  - Two cases of thyroid rupture after blunt cervical trauma.
AB  - The consequences of thyroid gland rupture following blunt cervical trauma can be
      quite grave. Almost all of these cases are associated with preexisting thyroid
      lesions; the traumatic rupture of a previously normal thyroid gland is very rare.
      Both surgical and nonsurgical management techniques have been advocated for
      thyroid injuries, but there is still no consensus on treatment. We report cases
      of thyroid gland rupture following blunt cervical trauma in 2 patients: a 24-year
      old man with a previously normal thyroid and an 8-year-old boy with a preexisting
      thyroid nodule. The man was treated surgically and the boy was treated
      conservatively. Based on our experience with these cases and our review of the
      literature, we propose treatment guidelines for thyroid injuries. 

PMID- 26214675
TI  - Nasal myiasis: A case report.
AB  - Nasal myiasis is a rare condition, with only a few reported cases and no
      treatment consensus. We propose a conservative treatment approach with saline
      irrigation and debridement. Two patients in the ICU of Norfolk General Hospital,
      a tertiary academic referral center, presented simultaneously with nasal myiasis.
      Both patients were negative for necrotic masses or tumors, and neither patient
      had any contributory medical comorbidities. Both patients were treated
      conservatively with a single dose of pyrantel pamoate, daily sinus irrigation
      with saline, and daily bedside endoscopic debridement. After 2 days, the nasal
      myiasis resolved, and both patients recovered without sequelae. We conclude that
      this conservative, nonsurgical approach to management is both safe and effective.

PMID- 26214676
TI  - Radiographic findings of a well-differentiated sinonasal neuroendocrine neoplasm:
      Case report and review of the literature.
AB  - Typical carcinoid is a rare tumor among other neuroendocrine neoplasms that occur
      in the nasal cavity. Only a few cases of typical carcinoids in the nasal cavity
      have been reported. We report a case of typical carcinoid of the nasal cavity in
      a 61-year-old man who had a history of persistent nasal obstruction and epistaxis
      for approximately 17 years. Computed tomography revealed a huge, lobulated mass
      in the nasal cavity with extension into the posterior sphenoid sinus. Extensive
      bone destruction could be seen in the neighboring sphenoid sinus. MR imaging
      suggested that the tumor was close to the dura. The final histologic evaluation
      of the excised biopsy specimen yielded a diagnosis of a well-differentiated
      neuroendocrine neoplasm (typical carcinoid). In this article, the relevant
      reports in the literature are reviewed, and the role of radiographic findings on
      tumor diagnosis and on the establishment of a surgery plan is emphasized. 

PMID- 26214677
TI  - Upper aerodigestive amyloidosis.

PMID- 26214678
TI  - The ostium of the posterior ethmoid sinus seen in the superior meatus.

PMID- 26214679
TI  - Cervical necrotizing fasciitis as a complication of acute epiglottitis managed
      with minimally aggressive surgical intervention: Case report.
AB  - Cervical necrotizing fasciitis secondary to epiglottitis is rare. The standard
      treatment of this severe condition has long been early and aggressive surgical
      debridement and adequate antimicrobial therapy. We report the case of an
      immunocompetent 59-year-old man who developed cervical necrotizing fasciitis as a
      complication of acute epiglottitis. We were able to successfully manage this
      patient with conservative surgical treatment (incision and drainage, in addition
      to antibiotic therapy) that did not involve aggressive debridement. 

PMID- 26214680
TI  - Cervical lipoblastoma: An uncommon presentation.
AB  - Lipoblastoma is extremely rare and mainly occurs in children younger than 3 years
      old. It is predominantly found in the extremities and trunk. Head and neck region
      occurrences are rare; only 4 such cases involving patients who presented with
      stridor have been previously reported. We report the fifth case of lipoblastoma
      of the neck with stridor in a 9-year-old girl, which had gradually worsened over
      the previous year. Imaging showed a retrotracheal mass extending superiorly to
      the thyroid level and inferiorly to below the carina of the trachea. Total
      resection of the tumor was performed, and the histopathologic findings were
      consistent with lipoblastoma. Postoperatively, the patient was well with no
      complications. 

PMID- 26214681
TI  - Manipulation of health span and function by dietary caloric restriction mimetics.
AB  - After nearly a century of rigorous investigation and testing, dietary caloric
      restriction (CR) remains the most robust and reproducible method for slowing
      aging and maintaining health, function, and vitality. This intervention has been
      applied to species across the evolutionary spectrum, but for a number of reasons,
      practical applicability to humans has been questioned. To overcome these issues,
      we initiated the field of CR mimetics in 1998 and have observed its development
      into a full-fledged antiaging industry. Basically, strategies that enable
      individuals to obtain the biological benefits of CR without reducing actual food
      intake can be considered CR mimetics, whether functional, pharmaceutical,
      nutraceutical, or other. Some of the best known candidates include resveratrol
      and related agents, the antidiabetic drug metformin, and rapamycin and other mTOR
      regulators. While the mechanisms of action vary, these and essentially all CR
      mimetic candidates work through at least some of the same pathways as actual CR.
      While the entire field continues to evolve rapidly, the current status will be
      reviewed here, with particular focus on recent developments, the most practical
      relevance and applicability for potential consumers, and new strategies for the
      future. 

PMID- 26214682
TI  - Semitransparent polymer solar cells with simultaneously improved efficiency and
      color rendering index.
AB  - Herein, we demonstrate a kind of high performance semi-transparent polymer solar
      cell (STPSC) with a significantly improved color rendering index (CRI) and power
      conversion efficiency (PCE) by introducing one-dimensional photonic crystals
      (1DPCs), which are intentionally designed to strongly reflect the pristine weak
      absorbed light to flatten the concavo-convex transmittance spectrum of STPSCs.
      The transmitted light from the STPSC device with 4 pairs of 1DPCs under AM 1.5G
      illumination shows extraordinary color rendering capacities, which contribute an
      increased CRI from 79 to 91, combined with an enhanced PCE from 4.14% to 5.01%
      compared to devices without 1DPCs. The simultaneously improved optical and
      electrical performance suggests that STPSCs can provide a unique feature, which
      is suitable for building integrated photovoltaic applications. 

PMID- 26214684
TI  - Shamba Maisha: randomized controlled trial of an agricultural and finance
      intervention to improve HIV health outcomes.
AB  - OBJECTIVES: Food insecurity and HIV/AIDS outcomes are inextricably linked in sub
      Saharan Africa. We report on health and nutritional outcomes of a multisectoral
      agricultural intervention trial among HIV-infected adults in rural Kenya. DESIGN:
      This is a pilot cluster randomized controlled trial. METHODS: The intervention
      included a human-powered water pump, a microfinance loan to purchase farm
      commodities, and education in sustainable farming practices and financial
      management. Two health facilities in Nyanza Region, Kenya were randomly assigned
      as intervention or control. HIV-infected adults 18 to 49 years' old who were on
      antiretroviral therapy and had access to surface water and land were enrolled
      beginning in April 2012 and followed quarterly for 1 year. Data were collected on
      nutritional parameters, CD4 T-lymphocyte counts, and HIV RNA. Differences in
      fixed-effects regression models were used to test whether patterns in health
      outcomes differed over time from baseline between the intervention and control
      arms. RESULTS: We enrolled 72 and 68 participants in the intervention and control
      groups, respectively. At 12 months follow-up, we found a statistically
      significant increase in CD4 cell counts (165 cells/MUl, P < 0.001) and proportion
      virologically suppressed in the intervention arm compared with the control arm
      (comparative improvement in proportion of 0.33 suppressed, odds ratio 7.6, 95%
      confidence interval: 2.2-26.8). Intervention participants experienced significant
      improvements in food security (3.6 scale points higher, P < 0.001) and frequency
      of food consumption (9.4 times per week greater frequency, P = 0.013) compared to
      controls. CONCLUSION: Livelihood interventions may be a promising approach to
      tackle the intersecting problems of food insecurity, poverty and HIV/AIDS
      morbidity.

PMID- 26214685
TI  - A descriptivist approach to trait conceptualization and inference.
AB  - In their recent article, How Functionalist and Process Approaches to Behavior Can
      Explain Trait Covariation, Wood, Gardner, and Harms (2015) underscore the need
      for more process-based understandings of individual differences. At the same
      time, the article illustrates a common error in the use and interpretation of
      latent variable models: namely, the misuse of models to arbitrate issues of
      causation and the nature of latent variables. Here, we explain how latent
      variables can be understood simply as parsimonious summaries of data, and how
      statistical inference can be based on choosing those summaries that minimize
      information required to represent the data using the model. Although Wood,
      Gardner, and Harms acknowledge this perspective, they underestimate its
      significance, including its importance to modeling and the conceptualization of
      psychological measurement. We believe this perspective has important implications
      for understanding individual differences in a number of domains, including
      current debates surrounding the role of formative versus reflective latent
      variables.

PMID- 26214683
TI  - Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated
      with Poor Survival.
AB  - Oral squamous cell carcinoma (OSCC) is an aggressive disease accounting for more
      than 260,000 cancer cases diagnosed and 128,000 deaths worldwide. A large
      majority of cancer deaths result from cancers that have metastasized beyond the
      primary tumor. The relationship between genetic changes and clinical outcome can
      reflect the biological events that promote cancer's aggressive behavior, and
      these can serve as molecular markers for improved patient management and
      survival. To this end, epithelial-mesenchymal transition (EMT) is a major process
      that promotes tumor invasion and metastasis, making EMT-related proteins
      attractive diagnostic biomarkers and therapeutic targets. In this study, we used
      immunohistochemistry to study the expression of a panel of transcription factors
      (TWIST1, SNAI1/2, ZEB1 and ZEB2) and other genes intimately related to EMT (CDH1
      and LAMC2) at the invasive tumor front of OSCC tissues. The association between
      the expression of these proteins and clinico-pathological parameters were
      examined with Pearson Chi-square and correlation with survival was analyzed using
      Kaplan Meier analysis. Our results demonstrate that there was a significant
      differential expression of CDH1, LAMC2, SNAI1/2 and TWIST1 between OSCC and
      normal oral mucosa (NOM). Specifically, CDH1 loss was significantly associated
      with Broder's grading, while diffused LAMC2 was similarly associated with non
      cohesive pattern of invasion. Notably, co-expression of TWIST1 and ZEB2 in OSCC
      was significantly associated with poorer overall survival, particularly in
      patients without detectable lymph node metastasis. This study demonstrates that
      EMT-related proteins are differentially expressed in OSCC and that the co
      expression of TWIST1 and ZEB2 could be of clinical value in identifying patients
      with poor survival for appropriate patient management. 

PMID- 26214686
TI  - Concentric Forster resonance energy transfer imaging.
AB  - Concentric Forster resonance energy transfer (cFRET) configurations based on
      semiconductor quantum dots (QDs) are promising probes for biological sensing
      because they offer multiplexing capability in a single vector with robust
      ratiometric detection by exploiting a network of FRET pathways. To expand the
      scope and utility of cFRET probes, it is necessary to develop and validate cFRET
      imaging methodology. In this technical note, we present such a methodology using
      a protease-sensitive cFRET configuration that comprises a green-emitting QD,
      Alexa Fluor 555 (A555), and Alexa Fluor 647 (A647). Photoluminescence (PL) images
      were acquired with three filter-based emission channels to permit measurement of
      A555/QD and A647/QD PL ratios. With reference to calibration samples, these PL
      ratios were used to calculate quantitative progress curves for proteolytic
      activity in regions of interest in the acquired images. Importantly, the imaging
      methodology reproduces quantitative results obtained with a monochromator-based
      fluorescence plate reader. Spatiotemporal resolution is demonstrated by tracking
      the activity of two prototypical proteases, trypsin and chymotrypsin, as they
      diffuse down the length of a capillary. This methodology is expected to enable
      the future use of cFRET probes for cellular sensing and other imaging assays. 

PMID- 26214687
TI  - A Screen for Epigenetically Silenced microRNA Genes in Gastrointestinal Stromal
      Tumors.
AB  - BACKGROUND: Dysregulation of microRNA (miRNA) has been implicated in
      gastrointestinal stromal tumors (GISTs) but the mechanism is not fully
      understood. In this study, we aimed to explore the involvement of epigenetic
      alteration of miRNA genes in GISTs. METHODS: GIST-T1 cells were treated with 5
      aza-2'-deoxycytidine (5-aza-dC) and 4-phenylbutyric acid (PBA), after which miRNA
      expression profiles were analyzed using TaqMan miRNA arrays. DNA methylation was
      then analyzed using bisulfite pyrosequencing. The functions of miRNAs were
      examined using MTT assays, wound-healing assays, Boyden chamber assays and
      Matrigel invasion assays. Gene expression microarrays were analyzed to assess
      effect of ectopic miRNA expression in GIST-T1 cells. RESULTS: Of the 754 miRNAs
      analyzed, 61 were significantly upregulated in GIST-T1 cells treated with 5-aza
      dC plus PBA. Among those, 21 miRNA genes were associated with an upstream CpG
      island (CGI), and the CGIs of miR-34a and miR-335 were frequently methylated in
      GIST-T1 cells and primary GIST specimens. Transfection of miR-34a or miR-335
      mimic molecules into GIST-T1 cells suppressed cell proliferation, and miR-34a
      also inhibited migration and invasion by GIST-T1 cells. Moreover, miR-34a
      downregulated a number of predicted target genes, including PDGFRA. RNA
      interference-mediated knockdown of PDGFRA in GIST-T1 cells suppressed cell
      proliferation, suggesting the tumor suppressive effect of miR-34a is mediated, at
      least in part, through targeting PDGFRA. CONCLUSIONS: Our results suggest that
      miR-34a and miR-335 are candidate tumor suppressive miRNAs in GISTs, and that
      they are frequent targets of epigenetic silencing in GISTs.

PMID- 26214688
TI  - Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism
      of Liver Fibrosis in Hepatitis C.
AB  - BACKGROUND: Chronic hepatitis C is a major cause of liver fibrosis and cirrhosis.
      It is generally accepted that inflammation that occurs in response to hepatocyte
      infection by the hepatitis C virus (HCV) is the main mechanism that triggers
      myofibroblast differentiation and stimulation in chronic hepatitis C. The aim of
      this study was to determine if HCV might infect human liver myofibroblasts (HLMF)
      and directly stimulate their fibrogenic activities. METHODS: We evaluated the
      expression of the viral entry receptors, levels of HCV-RNA and HCV-protein and
      the expression of fibrosis markers in HLMF by using quantitative PCR, western
      blot and immunofluorescence analyses. Pseudoparticles (HCVpp) and cell culture
      derived HCV (HCVcc) were used to study the ability of HLMF to support viral
      entry, replication and fibrosis induction. RESULTS: We showed that HLMF expressed
      all known molecules of the HCV receptor complex, i.e. CD81, LDL-R, scavenger
      receptor-BI, claudin-1 and occludin. These cells were also permissive to HCVpp
      entry. Inoculation with HCVcc caused short-term infection of these cells, as
      shown by their content in positive- and negative-strand HCV RNA, in core and NS3
      viral proteins, and by their release of core protein levels in the culture
      supernatants. HCV infection stimulated myofibroblastic differentiation,
      proliferation and collagen production in these cells. In addition, evidence of in
      vivo infection was provided by the detection of positive- and negative-strand HCV
      RNA in preparations of HLMF obtained from HCV-infected patients. CONCLUSION:
      These findings indicate that HCV infection of HLMF can occur and trigger
      extracellular matrix overproduction, thereby contributing to the development of
      HCV-related liver fibrosis.

PMID- 26214689
TI  - Genetic Loci Associated with Allergic Sensitization in Lithuanians.
AB  - Allergic rhinitis (AR) is a common and complex disease. It is associated with
      environmental as well as genetic factors. Three recent genome-wide association
      studies (GWAS) reported altogether 47 single nucleotide polymorphisms (SNPs)
      associated with AR or allergic sensitization (AS) in Europeans and North
      Americans. Two follow up studies in Swedish and Chinese replicated 15
      associations. In these studies individuals were selected based on the self
      reported AR, or AR/AS diagnosed using blood IgE test or skin prick test (SPT),
      which were performed often without restriction to specific allergens. Here we
      performed third replication study in Lithuanians. We used SPT and carefully
      selected set of allergens prevalent in Lithuania, as well as Illumina Core Exome
      chip for SNP detection. We genotyped 270 SPT-positive individuals (137 Betulaceae
      -, 174 Poaceae-, 199 Artemisia-, 70 Helianthus-, 22 Alternaria-, 22 Cladosporium
      , 140 mites-, 95 cat- and 97 dog dander-sensitive cases) and 162 SPT-negative
      controls. We found altogether 13 known SNPs associated with AS (p <=0.05). Three
      SNPs were found in Lithuanians sensitive to several allergens, and 10 SNPs were
      found in Lithuanians sensitive to a certain allergen. For the first time, SNP
      rs7775228:C was associated with patient sensitivity to dog allergens (F_A=0,269,
      F_U=0.180, P=0.008). Thus, careful assessment of AS allowed us to detect known
      genetic variants associated with AS/AR in relatively small cohort of Lithuanians.

PMID- 26214690
TI  - CXCR4 Antagonism Attenuates the Development of Diabetic Cardiac Fibrosis.
AB  - Heart failure (HF) is an increasingly recognized complication of diabetes.
      Cardiac fibrosis is an important causative mechanism of HF associated with
      diabetes. Recent data indicate that inflammation may be particularly important in
      the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism
      by which cardiac fibrosis develops and to specifically investigate the role of
      the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin
      treated mice) or type II diabetes (Israeli Sand-rats) and controls were
      randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control.
      Additional groups of mice also underwent bone marrow transplantation (GFP+ donor
      marrow) to investigate the potential role of bone marrow derived cell
      mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models
      of diabetes were accompanied by the development of significant cardiac fibrosis.
      CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes,
      similar in magnitude to that seen with candesartan. In contrast to candesartan,
      the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure
      independent manner. Whilst the induction of diabetes did not increase the overall
      myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells
      expressing the fibroblast marker alpha-smooth muscle actin and this was
      attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by
      increased levels of circulating regulatory T cells. Taken together the current
      data indicate that pharmacological inhibition of CXCR4 significantly reduces
      diabetes induced cardiac fibrosis, providing a potentially important therapeutic
      approach. 

PMID- 26214691
TI  - Optimization of Causative Factors for Landslide Susceptibility Evaluation Using
      Remote Sensing and GIS Data in Parts of Niigata, Japan.
AB  - This paper assesses the potentiality of certainty factor models (CF) for the best
      suitable causative factors extraction for landslide susceptibility mapping in the
      Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a
      landslide inventory map provided by National Research Institute for Earth Science
      and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the
      landslides in the inventory to be used for building the CF based model; (ii) 30%
      of the landslides to be used for the validation purpose. A spatial database with
      fifteen landslide causative factors was then constructed by processing ALOS
      satellite images, aerial photos, topographical and geological maps. CF model was
      then applied to select the best subset from the fifteen factors. Using all
      fifteen factors and the best subset factors, landslide susceptibility maps were
      produced using statistical index (SI) and logistic regression (LR) models. The
      susceptibility maps were validated and compared using landslide locations in the
      validation data. The prediction performance of two susceptibility maps was
      estimated using the Receiver Operating Characteristics (ROC). The result shows
      that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is
      slightly higher than those obtained from the SI model (AUC = 0.801). Further, it
      is noted that the SI and LR models using the best subset outperform the models
      using the fifteen original factors. Therefore, we conclude that the optimized
      factor model using CF is more accurate in predicting landslide susceptibility and
      obtaining a more homogeneous classification map. Our findings acknowledge that in
      the mountainous regions suffering from data scarcity, it is possible to select
      key factors related to landslide occurrence based on the CF models in a GIS
      platform. Hence, the development of a scenario for future planning of risk
      mitigation is achieved in an efficient manner. 

PMID- 26214692
TI  - Determinants of Children's Exhaled Nitric Oxide: New Insights from Quantile
      Regression.
AB  - While the fractional concentration of exhaled nitric oxide (FeNO) has proven
      useful in asthma research, its exact role in clinical care remains unclear, in
      part due to unexplained inter-subject heterogeneity. In this study, we assessed
      the hypothesis that the effects of determinants of the fractional concentration
      of exhaled nitric oxide (FeNO) vary with differing levels of FeNO. In a
      population-based cohort of 1542 school children aged 12-15 from the Southern
      California Children's Health Study, we used quantile regression to investigate if
      the relationships of asthma, socio-demographic and clinical covariates with FeNO
      vary across its distribution. Differences in FeNO between children with and
      without asthma increased steeply as FeNO increased (Estimated asthma effects (in
      ppb) at selected 20th, 50th and 80th percentiles of FeNO are 2.4, 6.3 and 22.2,
      respectively) but the difference was steeper with increasing FeNO in boys and in
      children with active rhinitis (p-values<0.01). Active rhinitis also showed
      significantly larger effects on FeNO at higher concentrations of FeNO (Estimated
      active rhinitis effects (in ppb) at selected 20th, 50th and 80th percentiles of
      FeNO are 2.1, 5.7 and 14.3, respectively). Boys and children of Asian descent had
      higher FeNO than girls and non-Hispanic whites; these differences were
      significantly larger in those with higher FeNO (p-values<0.01). In summary,
      application of quantile regression techniques provides new insights into the
      determinants of FeNO showing substantially varying effects in those with high
      versus low concentrations. 

PMID- 26214693
TI  - Clinical Parameters vs Cytokine Profiles as Predictive Markers of IgE-Mediated
      Allergy in Young Children.
AB  - BACKGROUND: Allergy afflicts one third of children, negatively impacting their
      quality of life and generating a significant socio-economic burden. To this day,
      this disorder remains difficult to diagnose early in young patients, with no
      predictive test available. OBJECTIVE: This study was designed to correlate
      cytokine profiles with clinical phenotypes of allergy development. METHODS: Three
      hundred patients were recruited and followed from birth to 18 months of age. They
      were given a clinical exam at birth and at 2, 6, 12, and 18 months of age, with
      skin prick tests at 6, and 18 months, in order to have a record of their medical
      history and determine their allergic status. In addition, mononuclear cells from
      131 patients were isolated from cord blood and from peripheral blood samples at
      2, 6 and 18 months of age, to analyse their cytokine and chemokine production.
      RESULTS: Cord blood mononuclear cells (CBMCs) from future Immunoglobulin (Ig) E
      mediated allergic children produced significantly less Interleukin (IL)-12p70 and
      IL-15 than cells from the rest of the cohort. Multivariate analyses revealed that
      the best predictive model of allergy was built on cytokine data, whereas the best
      predictive model of IgE-mediated allergy was built on clinical parameters.
      CONCLUSIONS AND CLINICAL RELEVANCE: Although univariate analyses can yield
      interesting information regarding the immune responses of allergic children,
      finding predictive markers of the disorder will likely rely on monitoring
      multiple parameters. Nonetheless these analyses suggest a potential key role for
      IL-15 in the development of atopic disease. In addition, the study highlights the
      importance of clinical parameters in predicting the development of IgE-mediated
      allergy.

PMID- 26214694
TI  - Three-Dimensional Power Doppler Ultrasonography for Diagnosing Abnormally
      Invasive Placenta and Quantifying the Risk.
AB  - OBJECTIVE: To test an objective ultrasound marker for diagnosing the presence and
      severity of abnormally invasive placenta. METHODS: Women at risk of abnormally
      invasive placenta underwent a three-dimensional power Doppler ultrasound scan.
      The volumes were examined offline by a blinded observer. The largest area of
      confluent three-dimensional power Doppler signal (Area of Confluence [Acon], cm)
      at the uteroplacental interface was measured and compared in women subsequently
      diagnosed with abnormally invasive placenta and women in a control group who did
      not have abnormally invasive placenta. Receiver operating characteristic curves
      were plotted for prediction of abnormally invasive placenta and abnormally
      invasive placenta requiring cesarean hysterectomy. RESULTS: Ninety-three women
      were recruited. Results were available for 89. Abnormally invasive placenta was
      clinically diagnosed in 42 women; 36 required hysterectomy and had abnormally
      invasive placenta confirmed histopathologically. Median and interquartile range
      for Acon was greater for abnormally invasive placenta (44.2 [31.4-61.7] cm)
      compared with women in the control group (4.5 cm [2.9-6.6], P<.001) and even
      greater in the 36 requiring hysterectomy (46.6 cm [37.2-72.6], P<.001). Acon rose
      with histopathologic diagnosis: focal accreta (32.2 cm [17.2-57.3]), accreta
      (59.6 cm [40.1-89.9]), and percreta (46.6 cm [37.5-71.5]; P<.001 analysis of
      variance for linear trend). Receiver operating characteristic analysis for
      prediction of abnormally invasive placenta revealed that with an Acon of 12.4 cm
      or greater, 100% sensitivity (95% confidence interval [CI] 91.6-100) could be
      obtained with 92% specificity (95% CI 79.6-97.6); area under the curve is 0.99
      (95% CI 0.94-1.0). For prediction of abnormally invasive placenta requiring
      hysterectomy, 100% sensitivity (95% CI 90.3-100) can be obtained with an Acon of
      17.4 cm or greater with 87% specificity (95% CI 74.7-94.5; area under the curve
      0.98 [0.93-1.0]). CONCLUSION: The marker Acon provides a quantitative means for
      diagnosing abnormally invasive placenta and assessing severity. If further
      validated, subjectivity could be eliminated from the diagnosis of abnormally
      invasive placenta. LEVEL OF EVIDENCE: II.

PMID- 26214695
TI  - Virulence Factors of Streptococcus pneumoniae. Comparison between African and
      French Invasive Isolates and Implication for Future Vaccines.
AB  - BACKGROUND: Many surface proteins thought to promote Streptocococcus pneumoniae
      virulence have recently been discovered and are currently being considered as
      future vaccine targets. We assessed the prevalence of 16 virulence genes among
      435 S. pneumoniae invasive isolates from France and the "African meningitis belt"
      region, with particular focus on serotype 1 (Sp1), to compare their geographical
      distribution, assess their association with site of infection and evaluate their
      potential interest as new vaccine candidates. METHODS: Detection by PCR of pspA
      (+families), pspC (+pspC.4), pavA, lytA, phtA,B,D,E, nanA,B,C, rrgA (Pilus-1),
      sipA (Pilus-2), pcpA and psrp was performed on all isolates, as well as
      antibiotic resistance testing and MLVA typing (+MLST on 54 representative
      strains). Determination of ply alleles was performed by sequencing (Sp1
      isolates). RESULTS: MLVA and virulence genes profiles segregated Sp1 isolates
      into 2 groups that followed continent distribution. The ply allele 5 and most of
      the genes that were variable (nanC, Pilus-2, psrp, pcpA, phtD) were present in
      the French Sp1 isolates (PMEN clone Sweden(1)-28, ST306) but absent from the
      African ones. Whereas all African Sp1 isolates clustered into a single MLST CC
      (CC217), MLVA distinguished two CCs that followed temporal evolution. Pilus-2 and
      psrp were more prevalent in bacteraemic pneumonia yielded isolates and phtB in
      meningitis-related isolates. Considering vaccine candidates, phtD was less
      prevalent than anticipated (50%) and pcpA varied importantly between France and
      Africa (98% versus 34%). Pilus-1 was carried by 7-11% of isolates and associated
      with beta-lactams resistance. CONCLUSIONS: Most virulence genes were carried by
      the European ST306 clone but were lacking on Sp1 isolates circulating in the
      African meningitis belt, where a more serious pattern of infection is observed.
      While virulence proteins are now considered as vaccine targets, the geographical
      differences in their prevalence could affect the efficacy expected from future
      vaccines.

PMID- 26214696
TI  - Promoting Policy, Systems, and Environment Change to Prevent Chronic Disease:
      Lessons Learned From the King County Communities Putting Prevention to Work
      Initiative.
AB  - CONTEXT: Initiatives that convene community stakeholders to implement policy,
      systems, environment, and infrastructure (PSEI) change have become a standard
      approach for promoting community health. OBJECTIVE: To assess the PSEI changes
      brought about by the King County, Washington, Communities Putting Prevention to
      Work initiative and describe how initiative structures and processes contributed
      to making changes. DESIGN: The impact evaluation used a logic model design,
      linking PSEI changes to longer-term behavioral impacts in healthy eating active
      living and tobacco use and exposure. Qualitative methods, including stakeholder
      interviews and surveys, were used to identify initiative success factors.
      SETTING: Communities Putting Prevention to Work activities occurred throughout
      King County, with a focus on 7 low-income communities in South Seattle/King
      County. PARTICIPANTS: The focus communities had a combined population of 652 000,
      or 35% of the county total, with lower incomes and higher rates of physical
      inactivity, tobacco use, poor diet, and chronic disease. INTERVENTION: Twenty
      four PSEI strategies were pursued by organizations in sectors including schools,
      local governments, and community organizations, supported by the public health
      department. There were 17 healthy eating active living strategies (eg,
      enhancements to school menus, city planning policies) and 7 tobacco strategies
      (eg, smoke-free policies in schools, housing, and hospitals). MAIN OUTCOME
      MEASURE: PSEI changes made and numbers of residents reached. RESULTS: Twenty-two
      of the 24 strategies achieved significant progress toward implementing PSEI
      changes. The most common success factor was a "dyad" consisting of a dedicated
      technical assistance provider-either an outside consultant or public health
      department staff-working closely with a champion from the participating
      organizations to bring about PSEI changes. CONCLUSIONS: An initiative structure
      that creates and supports external consultant/internal organizational champion
      dyads in key community sectors offers a promising approach that may be adopted by
      similar community health efforts in the future.

PMID- 26214704
TI  - Piezofluorochromic Metal-Organic Framework: A Microscissor Lift.
AB  - We have successfully constructed a metal-organic framework, denoted as PCN-128W,
      starting from chromophoric linker and zirconium salt. PCN-128W exhibits
      interesting piezofluorochromic behavior, the color reversibly changes from white
      to yellow and so does the emission maximum from 470 to 538 nm. The stepwise
      fluorescence change was monitored by fluorospectroscopy which demonstrated
      gradual shift of the emission maximum when sequential compression was exerted. In
      order to gain deep insights into the piezofluorochromic mechanism, both the white
      and yellow phases are structurally characterized. 

PMID- 26214703
TI  - The Molecular Characterization of Intestinal Explant HIV Infection Using
      Polymerase Chain Reaction-Based Techniques.
AB  - The ex vivo mucosal explant model is frequently used to test the efficacy of
      microbicides that have the potential for preventing HIV-1 transmission. The
      conventional assessment of product efficacy has been the extent of HIV-1 p24
      suppression in supernatant fluids sampled up to day 14 after HIV-1 challenge ex
      vivo. The purpose of this study was to determine if measurement of HIV-1 nucleic
      acids by real-time PCR and HIV-1 integration by Alu-gag PCR provides advantages
      with regard to monitoring HIV-1 infection in explants. Rectal biopsies from HIV-1
      negative individuals were challenged with 1 * 10(5) virions/ml of HIV-1BaL or HIV
      1CH077 ex vivo. HIV-1 RNA and HIV-1 p24 in supernatant fluids and HIV-1 nucleic
      acids and integrated provirus in individual biopsies were measured at days 1-14
      after infection. HIV-1 RNA and proviral DNA were measured by quantitative real
      time PCR (qRT-PCR) while integrated virus was detected by Alu-gag PCR. Real-time
      PCR assays detecting HIV-1 DNA and RNA performed similarly provided that the
      infecting virus sequences were a good match with the sequences of the assay
      primers and probes. Increased HIV-1 nucleic acid levels and DNA integration were
      measurable on days 11 and 14 after infection. The magnitude of explant infection
      was similar after challenge with HIV-1BaL and HIV-1CH077, although the trajectory
      of infection was delayed in the HIV-1CH077-infected biopsies. In the majority of
      experiments, qRT-PCR did not appreciably shorten the time necessary to detect
      evidence of HIV-1 infection. 

PMID- 26214705
TI  - Usefulness of mean platelet volume for predicting stroke risk in paroxysmal
      atrial fibrillation patients.
AB  - Atrial fibrillation is the most common sustained arrhythmia in clinical practice.
      It is important to specify patients with a high risk of thromboembolus due to
      elevated procoagulant and prothrombotic state. The aim of this study is to assess
      the relation of stroke/transient ischaemic attack (TIA) with mean platelet volume
      (MPV), which is an indicator of platelet activation in patients with paroxysmal
      atrial fibrillation (PAF). Patients with PAF were enrolled in this study during
      years of 2012-2014. Patients were divided into two groups according to the
      presence or absence of stroke/TIA. Demographic data were registered and
      CHA2DS2VASc scores of patients were calculated. It was investigated whether there
      was a difference among groups regarding MPV levels. Ninety patients, 31 of whom
      had history of stroke/TIA (symptomatic group), were enrolled to study.
      CHA2DS2VASc score of symptomatic group was 4.77 +/- 1.26, while CHA2DS2VASc score
      of asymptomatic group was 2.63 +/- 1.41. Nevertheless, there was not any
      difference regarding CHA2DS2VASc score among two groups when 2 points due to
      stroke/TIA were subtracted in symptomatic patients. MPV was detected higher in
      symptomatic patients than asymptomatic patients (11.1 +/- 1.3 vs. 9.1 +/- 1.0 fL,
      P < 0.001, respectively). A value of 9.85 for the MPV ascertained with receiver
      operating characteristic (ROC) curve analysis to predict stroke/TIA was found to
      have a sensitivity of 87% and specificity of 78%. Elevated MPV levels were
      ascertained to be related with stroke/TIA in patients with PAF. Assessment of MPV
      apart from CHA2DS2VASc score in patients with PAF might be subsidiary to specify
      patients with an enhanced risk of stroke/TIA. 

PMID- 26214706
TI  - On the role of entropy in determining transport properties in metallic melts.
AB  - We performed ab initio molecular dynamics simulations to study the relationship
      between dynamic and structural properties of liquid Al1-xNix alloys along the T =
      1795 K isotherm. Our findings show a strong non-linear dependence of self
      diffusion coefficients and the viscosity as a function of composition, in fair
      agreement with available experimental data. We demonstrate that this non-linear
      dependence can be related to the detailed description of local structural
      ordering and more particularly to a pronounced increase of icosahedral short
      range order (ISRO) in the Ni-rich composition range. We evidence that the
      composition dependence of local structural ordering is not captured by the Stokes
      Einstein relation but can be understood in terms of the partial excess entropy
      approximated by the two-body contribution. 

PMID- 26214707
TI  - Refactoring the Six-Gene Photosystem II Core in the Chloroplast of the Green
      Algae Chlamydomonas reinhardtii.
AB  - Oxygenic photosynthesis provides the energy to produce all food and most of the
      fuel on this planet. Photosystem II (PSII) is an essential and rate-limiting
      component of this process. Understanding and modifying PSII function could
      provide an opportunity for optimizing photosynthetic biomass production,
      particularly under specific environmental conditions. PSII is a complex
      multisubunit enzyme with strong interdependence among its components. In this
      work, we have deleted the six core genes of PSII in the eukaryotic alga
      Chlamydomonas reinhardtii and refactored them in a single DNA construct.
      Complementation of the knockout strain with the core PSII synthetic module from
      three different green algae resulted in reconstitution of photosynthetic activity
      to 85, 55, and 53% of that of the wild-type, demonstrating that the PSII core can
      be exchanged between algae species and retain function. The strains, synthetic
      cassettes, and refactoring strategy developed for this study demonstrate the
      potential of synthetic biology approaches for tailoring oxygenic photosynthesis
      and provide a powerful tool for unraveling PSII structure-function relationships.

PMID- 26214708
TI  - Blunted neural response to rewards as a vulnerability factor for depression:
      Results from a family study.
AB  - Depressive disorders are associated with significant economic and public health
      burdens as well as increased morbidity. Yet, perhaps due to the heterogeneous
      nature of the disease, prevention and intervention efforts are only moderately
      efficacious. A better understanding of core mechanisms of depressive disorders
      might aid in the development of more targeted intervention, and perhaps help
      identify individuals at risk. One mechanism that may be particularly important to
      depressive phenotypes is reward insensitivity. Examination of neurobiological
      correlates of reward-processing, which should relate more directly to the
      neuropathology of depression, may be helpful in identifying liability for the
      disorder. To that end, we used a family study design to examine whether a neural
      response to rewards is a familial risk factor for depression in a sample of
      probands with a wide range of internalizing psychopathology, as well as their
      biological siblings. Event-related potentials were recorded during a simple
      forced-choice gambling paradigm, in which participants could either win or lose
      small amounts of money. Lower levels of positive affect in probands predicted a
      reduced neural response to rewards in siblings, even over and above the sibling's
      own level of positive and negative affect. Additionally, the neural response to
      rewards was familial (i.e., correlated among siblings). Combined, these analyses
      suggest that a blunted neural response to rewards may be useful in identifying
      individuals vulnerable to depressive illnesses.

PMID- 26214709
TI  - Ecological Engineering Approaches to Improve Hydraulic Properties of Infiltration
      Basins Designed for Groundwater Recharge.
AB  - Infiltration systems are increasingly used in urban areas for groundwater
      recharge. The reduction of sediment permeability by physical and/or biological
      processes is a major problem in management of infiltration systems often
      requiring expensive engineering operations for hydraulic performance maintenance.
      To reduce these costs and for the sake of sustainable development, we proposed to
      evaluate the ability of ecological engineering approaches to reduce the
      biological clogging of infiltration basins. A 36-day field-scale experiment using
      enclosures was performed to test the influences of abiotic (light reduction by
      shading) and biotic (introduction of the macrophyte Vallisneria spiralis (L.) or
      the gastropod Viviparus viviparus (Linnaeus, 1758)) treatments to limit benthic
      biofilm biomass and to maintain or even increase hydraulic performances. We
      coupled biological characterization of sediment (algal biomass, bacterial
      abundance, total organic carbon, total nitrogen, microbial enzymatic activity,
      photosynthetic activity, and photosystem II efficiency) with hydraulic
      conductivity measurements to assess the effects of treatments on sediment
      permeability. The grazer Viviparus viviparus significantly reduced benthic
      biofilm biomass and enhanced hydraulic conductivity. The other treatments did not
      produce significant changes in hydraulic conductivity although Vallisneria
      spiralis affected photosynthetic activity of biofilm. Finally, our results
      obtained with Viviparus viviparus are promising for the development of ecological
      engineering solutions to prevent biological fouling in infiltration systems.

PMID- 26214710
TI  - Role of the Cell Cycle Re-Initiation in DNA Damage Response of Post-Mitotic Cells
      and Its Implication in the Pathogenesis of Neurodegenerative Diseases.
AB  - Neurodegenerative diseases are often associated with both normal and premature
      aging. Resumption of the cell cycle by neurons induced by DNA damage may lead to
      their apoptosis, which contributes to the degeneration of neuronal tissue. Cell
      cycle and DNA replication proteins are frequently found in patients with
      neurodegenerative diseases. Oxidative stress, which is considered to play an
      important role in aging and pathogenesis of many neurodegenerative diseases, can
      induce DNA damage and stimulate cell cycle re-entry by neuronal cells. DNA damage
      activates ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3
      related (ATR), breast cancer 1 (BRCA1), E2F transcription factor 1 (E2F1), and
      other proteins that regulate the cell cycle, DNA damage repair, and apoptosis.
      Because the E2F complexes associate with histone-modifying enzymes, histone
      modifications, including histone acetylation and methylation, are required for
      cell cycle re-entry and may play a regulatory role in DNA repair or apoptosis.
      Aberrant cell cycle regulation has been shown to play a role in age-related
      macular degeneration (AMD) in which retinal cells are affected and in inclusion
      body myositis, which is characterized by muscle cell dysfunction. There is also
      evidence to suggest that cytostatic chemotherapy could decrease dementia in
      Alzheimer's disease and multiple myeloma, supporting the use of cell cycle
      inhibitors in the therapy of degenerative diseases. 

PMID- 26214712
TI  - Absence of superconductivity in fluorine-doped neptunium pnictide NpFeAsO.
AB  - X-ray diffraction, specific heat, magnetic susceptibility and inelastic x-ray
      scattering measurements on the transurarium oxypnictides NpFeAsO and
      NpFeAsO0.85F0.15 are presented. No superconductivity down to 2 K was observed
      upon fluorine doping, contrary to the structurally analogous rare-earth
      pnictides. No modification of the phonon density of states was observed upon
      doping with fluorine. We discuss our results in light of the latest experimental
      and theoretical studies on the role of phonons in the superconducting pnictide
      compounds. 

PMID- 26214711
TI  - Transgenic Wheat Expressing a Barley UDP-Glucosyltransferase Detoxifies
      Deoxynivalenol and Provides High Levels of Resistance to Fusarium graminearum.
AB  - Fusarium head blight (FHB), mainly caused by Fusarium graminearum, is a
      devastating disease of wheat that results in economic losses worldwide. During
      infection, F. graminearum produces trichothecene mycotoxins, including
      deoxynivalenol (DON), that increase fungal virulence and reduce grain quality.
      Transgenic wheat expressing a barley UDP-glucosyltransferase (HvUGT13248) were
      developed and evaluated for FHB resistance, DON accumulation, and the ability to
      metabolize DON to the less toxic DON-3-O-glucoside (D3G). Point-inoculation tests
      in the greenhouse showed that transgenic wheat carrying HvUGT13248 exhibited
      significantly higher resistance to disease spread in the spike (type II
      resistance) compared with nontransformed controls. Two transgenic events
      displayed complete suppression of disease spread in the spikes. Expression of
      HvUGT13248 in transgenic wheat rapidly and efficiently conjugated DON to D3G,
      suggesting that the enzymatic rate of DON detoxification translates to type II
      resistance. Under field conditions, FHB severity was variable; nonetheless,
      transgenic events showed significantly less-severe disease phenotypes compared
      with the nontransformed controls. In addition, a seedling assay demonstrated that
      the transformed plants had a higher tolerance to DON-inhibited root growth than
      nontransformed plants. These results demonstrate the utility of detoxifying DON
      as a FHB control strategy in wheat. 

PMID- 26214713
TI  - Safety and Efficacy of Fibrinolytic Therapy in Restoring Function of an
      Obstructed Tunneled Pleural Catheter.
AB  - RATIONALE: Tunneled pleural catheters have been established to be safe and
      effective in the management of recurrent symptomatic pleural effusions.
      Obstruction of the tunneled pleural catheter is rare; however, when obstructed
      the catheter fails to achieve its primary goal of symptom palliation. The
      management of pleural catheter obstruction has not been studied. OBJECTIVES: We
      aimed to determine if the use of intracatheter fibrinolytic therapy is safe and
      effective in restoring catheter function. METHODS: One hundred seventy-two
      patients with tunneled pleural catheters placed from 2009 to 2014 were reviewed
      to identify patients who received fibrinolysis for catheter obstruction, defined
      by a sudden reduction to less than 10 ml in pleural fluid drainage with fluid
      visualized in the thorax on ultrasound/radiography. The technique involved
      intracatheter instillation of 2 to 5 mg of alteplase, which was allowed to remain
      in the catheter for 60 to 120 minutes, after which drainage was performed.
      MEASUREMENTS AND MAIN RESULTS: Obstruction occurred in 37 pleural catheters at a
      median of 2 months from insertion. One hundred percent (37/37) of obstructed
      catheters resumed drainage after fibrinolytic instillation, from a median of 4 ml
      before to 300 ml after fibrinolysis (P < 0.001). Twenty-four (65%) were performed
      in an outpatient setting, and no complications were encountered during or after
      fibrinolytic therapy. There were 18 episodes of reobstruction, all of which were
      successfully treated with intracatheter fibrinolytic therapy without
      complication. CONCLUSIONS: Fibrinolytic instillation through a tunneled pleural
      catheter is safe and effective in restoring function of an obstructed catheter,
      as evidenced by the lack of complications and success in achieving catheter
      patency. The procedure can also be performed safely in an outpatient setting.
      Patients who experience catheter obstruction may be prone to reobstruction;
      however, fibrinolysis was safe and effective in reestablishing patency of the
      reobstructed catheter.

PMID- 26214714
TI  - The Lancet, Gaza and academic publishing: defending political engagement.

PMID- 26214716
TI  - Sociodemographic factors associated with anaemia in pregnancy at booking for
      antenatal care.
AB  - Late patronage of antenatal care by women in low-resource areas makes timely
      intervention at correcting anaemia difficult. This study aimed to identify
      modifiable sociodemographic factors that predict anaemia before commencing
      antenatal care and make appropriate recommendation. A survey of sociodemographic
      features and haemoglobin concentrations of 232 women booking for antenatal care
      was conducted. Anaemia was diagnosed in 119 (51.3%), of which 87 (37.5%) had mild
      anaemia and 32 (13.8%) were moderately anaemic. There was no severe anaemia.
      Anaemia was highest among respondents who were 35 years of age, Muslims, of Igbo
      ethnicity (64.3%), single (55.0%), student/unemployed (58.8%), nulliparous
      (57.3%) and those who registered at 21 weeks' gestation (54.2%). Only occupation
      of the woman showed association with anaemia before antenatal care (p 0.007). A
      personal source of income may reduce anaemia in pregnancy; and it is advisable to
      have a social welfare package for unemployed pregnant women.

PMID- 26214717
TI  - Self-Fulfilling Prophecies in Ability Settings.
AB  - Previous research has demonstrated that one person's expectations can influence
      the behavior of another person, thereby creating a self-fulfilling prophecy. This
      study examined the effects of ability-based expectations in an experiment in
      which some participants ("coaches") were assigned false expectations of the
      basketball free-throw shooting ability of other participants ("players"). Coaches
      allocated more opportunities to players for whom the false expectation was
      positive, and fewer shots to players for whom the false expectation was negative.
      In turn, players who were allocated more shots made a higher percentage of them,
      thereby confirming their coaches' expectations about their shooting ability, and
      were more confident in their shooting ability following the task, than players
      who were allocated fewer shots. 

PMID- 26214718
TI  - Integrating Substrateless Electrospinning with Textile Technology for Creating
      Biodegradable Three-Dimensional Structures.
AB  - The present study describes a unique way of integrating substrateless
      electrospinning process with textile technology. We developed a new collector
      design that provided a pressure-driven, localized cotton-wool structure in free
      space from which continuous high strength yarns were drawn. An advantage of this
      integration was that the textile could be drug/dye loaded and be developed into a
      core-sheath architecture with greater functionality. This method could produce
      potential nanotextiles for various biomedical applications. 

PMID- 26214719
TI  - Treatment of Sixth Nerve Palsy.

PMID- 26214720
TI  - "Why Does My Baby. . .Have a Large Blue Right Eye?". Congenital anterior
      staphyloma.

PMID- 26214721
TI  - Somewhere Over the Rainbow.

PMID- 26214722
TI  - The Natural History of Small-Angle Intermittent Exotropia.

PMID- 26214723
TI  - Idiopathic Frosted Branch Angiitis in a 2-Year-Old Boy.

PMID- 26214724
TI  - Acute Bilateral Leber Hereditary Optic Neuropathy.

PMID- 26214726
TI  - Introductory address for the American Pediatric Society's 2015 John Howland Award
      Recipient, Catherine D. DeAngelis.
AB  - Presented by Julia A. McMillan, MD, Professor of Pediatrics, Executive Vice
      Chair, Department of Pediatrics, and Associate Dean for Graduate Medical
      Education, Johns Hopkins University School of Medicine, at the 2015 Annual
      Meeting of the Pediatric Academic Societies, San Diego, CA. 

PMID- 26214727
TI  - American Pediatric Society 2015 presidential address: life's lessons learned.
AB  - Presented at the 2015 Annual Meeting of the American Pediatric Society, San
      Diego, California, USA. 

PMID- 26214725
TI  - Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: a
      pilot randomized placebo-controlled trial.
AB  - OBJECTIVE: Obsessive-compulsive disorder (OCD) affects approximately 2.5% of the
      population and is associated with significant morbidity. Many patients receive
      little benefit from the best available treatments, and even those who do respond
      often suffer from significant residual symptoms. Convergent evidence suggests
      that abnormalities in glutamate homeostasis and neurotransmission may contribute
      to OCD and that glutamate-modulating medications may be of benefit in patients
      whose symptoms are refractory to standard interventions. Small open-label trials
      of augmentation of serotonin reuptake inhibitor (SRI) pharmacotherapy with the
      glutamate modulator riluzole have suggested benefit in adults with refractory
      symptoms. We report a pilot randomized placebo-controlled trial of riluzole
      augmentation of ongoing SRI treatment in SRI-refractory patients. METHOD:
      Outpatients (n = 27) and inpatients (n = 11) with DSM-IV OCD on stable SRI
      pharmacotherapy were randomized between November 2006 and December 2012 to
      receive riluzole 50 mg or placebo twice a day and followed for 12 weeks after a 2
      week placebo lead-in phase. RESULTS: Riluzole was well tolerated; 1 patient
      experienced moderate nausea, but none discontinued treatment due to side effects.
      While there was nominally greater Y-BOCS improvement in the riluzole group (our
      primary outcome) compared to placebo, it did not reach statistical significance.
      In the outpatient subsample, a trend suggesting benefit from riluzole
      augmentation for obsessions (P = .056, 2-tailed, uncorrected) was found in a
      secondary analysis. Among outpatients, more achieved at least a partial response
      (> 25% improvement) with riluzole than with placebo (P = .02 in a secondary
      analysis). CONCLUSIONS: Riluzole may be of benefit to a subset of patients.
      Larger samples would be required to detect effects of the order suggested by the
      nominal improvement in our outpatient subsample. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00523718.

PMID- 26214728
TI  - High-Performance Pressure-Sensitive Adhesives from Renewable Triblock Copolymers.

PMID- 26214730
TI  - Atomistic Mechanisms for the Nucleation of Aluminum Oxide Nanoparticles.
AB  - A predictive model for nanoparticle nucleation has not yet been successfully
      achieved. Classical nucleation theory fails because the atomistic nature of the
      seed has to be considered. Indeed, geometrical structure as well as stoichiometry
      do not always match the bulk values. We present a fully microscopic approach
      based on a first-principle study of aluminum oxide clusters. We calculated stable
      structures of AlxOy and their associated thermodynamic properties. From these
      data, the chemical composition of a gas composed of aluminum and oxygen atoms can
      be calculated as a function of temperature, pressure, and aluminum to oxygen
      ratio. We demonstrate the accuracy of this approach in reproducing experimental
      results obtained with time-resolved spectroscopy of a laser-induced plasma from
      an Al2O3 target. We thus extended the calculation to lower temperatures, i.e.,
      longer time scales, to propose a scenario of composition gas evolution leading to
      the first alumina seeds. 

PMID- 26214729
TI  - N-Lipidated Peptide Dimers: Effective Antibacterial Agents against Gram-Negative
      Pathogens through Lipopolysaccharide Permeabilization.
AB  - Treating infections caused by multidrug-resistant Gram-negative pathogens is
      challenging, and there is concern regarding the toxicity of the most effective
      antimicrobials for Gram-negative pathogens. We hypothesized that conjugating a
      fatty acid moiety onto a peptide dimer could maximize the interaction with
      lipopolysaccharide (LPS) and facilitate the permeabilization of the LPS barrier,
      thereby improving potency against Gram-negative pathogens. We systematically
      designed a series of N-lipidated peptide dimers that are active against Gram
      negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). The
      optimized lipid length was 6-10 carbons. At these lipid lengths, the N-lipidated
      peptide dimers exhibited strong LPS permeabilization. Compound 23 exhibited
      synergy with select antibiotics in most of the combinations tested. 23 and 32
      also displayed rapid bactericidal activity. Importantly, 23 and 32 were
      nonhemolytic at 10 mg/mL, with no cellular or in vivo toxicity. These
      characteristics suggest that these compounds can overcome the limitations of
      current Gram-negative-targeted antimicrobials such as polymyxin B. 

PMID- 26214731
TI  - Pediatric Pathology In The Year 2050.
AB  - The study of pathology in fetuses, infants, and children had its beginnings in
      the mid-19th century. Now, 165 years later, hundreds of pediatric pathologists
      are in up-to-date practices throughout the world. They, and all medical
      practitioners, are just beginning to delve into the nanotechnical wave.
      Nanotechnology refers to the structure and activity of minute particles,
      molecules, compounds, and atoms. By 2050, as nanotechnical studies develop
      further, new diseases and variations of old diseases will be discovered.
      Aggregation of medical data from billions of people, a process known as crowd
      sourcing, will be digitally interconnected to the new findings with computers.
      Pediatric pathologists will contribute to this expanding science with new
      laboratory instruments, including ultramodern microscopes known as Omniscopes.
      Robots will be programmed to perform autopsies and process surgical specimens.
      Analyzers in chemistry, microbiology, hematology, and genetics will, in 2050,
      produce dozens or even hundreds of results within minutes. These advances will
      lead to better treatments and overall better health for everyone. 

PMID- 26214733
TI  - Half-sandwich rare-earth-catalyzed olefin polymerization, carbometalation, and
      hydroarylation.
AB  - The search for new catalysts for more efficient, selective chemical
      transformations and for the synthesis of new functional materials has been a long
      standing research subject in both academia and industry. To develop new
      generations of catalysts that are superior or complementary to the existing ones,
      exploring the potential of untapped elements is an important strategy. Rare-earth
      elements, including scandium, yttrium, and the lanthanides (La-Lu), constitute
      one important frontier in the periodic table. Rare-earth elements possess unique
      chemical and physical properties that are different from those of main-group and
      late-transition metals. The development of rare-earth-based catalysts by taking
      the advantage of these unique properties is of great interest and importance. The
      most stable oxidation state of rare-earth metals is 3+, which is difficult to
      change under many reaction conditions. The oxidative addition and reductive
      elimination processes often observed in catalytic cycles involving late
      transition metals are generally difficult in the case of rare-earth complexes.
      The 18-electron rule that is applicable to late-transition-metal complexes does
      not fit rare-earth complexes, whose structures are mainly governed by the sterics
      (rather than the electron numbers) of the ligands. In the lanthanide series (La
      Lu), the ionic radius gradually decreases with increasing atomic number because
      of the influence of the 4f electrons, which show poor shielding of nuclear
      charge. Rare-earth metal ions generally show strong Lewis acidity and
      oxophilicity. Rare-earth metal alkyl and hydride species are highly reactive,
      showing both nucleophilicity and basicity. The combination of these features,
      such as the strong nucleophilicity and moderate basicity of the alkyl and hydride
      species and the high stability, strong Lewis acidity, and unsaturated C-C bond
      affinity of the 3+ metal ions, can make rare-earth metals unique candidates for
      the formation of excellent single-site catalysts. This Account is intended to
      give an overview of our recent studies on organo rare-earth catalysis, in
      particular the synthesis and application of half-sandwich rare-earth alkyl
      complexes bearing monocyclopentadienyl ligands for olefin polymerization,
      carbometalation, and hydroarylation. Treatment of half-sandwich rare-earth
      dialkyl complexes having the general formula CpMR2 with an equimolar amount of an
      appropriate borate compound such as [Ph3C][B(C6F5)4] can generate the
      corresponding cationic monoalkyl species, which serve as excellent single-site
      catalysts for the polymerization and copolymerization of a wide range of olefin
      monomers such as ethylene, 1-hexene, styrene, conjugated and nonconjugated
      dienes, and cyclic olefins. The cationic half-sandwich rare-earth alkyl complexes
      can also catalyze the regio- and stereoselective alkylative alumination of
      alkenes and alkynes through insertion of the unsaturated C-C bond into the metal
      alkyl bond followed by transmetalation between the resulting new alkyl or alkenyl
      species and an alkylaluminum compound. Moreover, a combination of deprotonative C
      H bond activation of appropriate organic compounds such as anisoles and pyridines
      by the rare-earth alkyl species and insertion of alkenes into the resulting new
      metal-carbon bond can lead to catalytic C-H bond alkylation of the organic
      substrates. Most of these transformations are unique to the rare-earth catalysts
      with selectivity and functional group tolerance different from those of late
      transition-metal catalysts. 

PMID- 26214732
TI  - Outcomes of primary refractory multiple myeloma and the impact of novel
      therapies.
AB  - Over the past decade, use of novel agents, including immunomodulatory drugs
      (IMiDs) and proteasome inhibitors (PIs) has resulted in high response rates and
      improvement in overall survival (OS) for patients with multiple myeloma (MM);
      however, the prognostic significance of refractoriness to these agents when used
      as initial therapy has not been extensively studied. We reviewed the outcomes of
      816 consecutive patients treated for MM at our institution since 2006 to evaluate
      the survival difference between those achieving at least a partial response (PR)
      to induction therapy and those who were primary refractory. The median OS from
      start of therapy was significantly shorter for the primary refractory group at
      3.6 vs. 7.6 years for the responding patients (P < 0.001). The difference in
      median OS persisted when only patients receiving a novel agent as part of
      induction therapy were considered (3.6 vs. 7.9 years, P < 0.001) and in a 4-month
      landmark analysis (4.2 vs. 7.6 years, P < 0.001). The median OS for patients
      achieving a complete response (CR), very good partial response (VGPR), PR, or
      less than PR was not reached (NR), 6.1, 6.4, and 4.2 years from the 4-month
      landmark, respectively (P < 0.001). The comparatively poor outcomes of patients
      refractory to induction therapy in the current era of novel agents suggests that
      this high-risk subpopulation must be further studied for predictors of resistance
      and, when identified, should be targeted for clinical trials.

PMID- 26214734
TI  - Tuning the Optical Properties of Cesium Lead Halide Perovskite Nanocrystals by
      Anion Exchange Reactions.
AB  - We demonstrate that, via controlled anion exchange reactions using a range of
      different halide precursors, we can finely tune the chemical composition and the
      optical properties of presynthesized colloidal cesium lead halide perovskite
      nanocrystals (NCs), from green emitting CsPbBr3 to bright emitters in any other
      region of the visible spectrum, and back, by displacement of Cl(-) or I(-) ions
      and reinsertion of Br(-) ions. This approach gives access to perovskite
      semiconductor NCs with both structural and optical qualities comparable to those
      of directly synthesized NCs. We also show that anion exchange is a dynamic
      process that takes place in solution between NCs. Therefore, by mixing solutions
      containing perovskite NCs emitting in different spectral ranges (due to different
      halide compositions) their mutual fast exchange dynamics leads to homogenization
      in their composition, resulting in NCs emitting in a narrow spectral region that
      is intermediate between those of the parent nanoparticles. 

PMID- 26214735
TI  - Multicomponent Coupling Reaction Using Arynes: Synthesis of Xanthene Derivatives.
AB  - One-pot synthesis of xanthene derivatives was achieved by a route involving the
      cascade three-component coupling reaction of arynes with DMF and active
      methylenes followed by the SN2' reaction of three-component coupling products
      with thiols. The reactivity of three-component coupling products toward
      nucleophiles and the further conversion of oxygen heterocycles allowing facile
      incorporation of structural variety were studied. 

PMID- 26214736
TI  - Molecular dynamics of dibenz[a,h]anthracene and its metabolite interacting with
      lung surfactant phospholipid bilayers.
AB  - The interaction of dibenz[a,h]anthracene and its ultimate carcinogenic 3,4-diol
      1,2-epoxide with lung surfactant phospholipid bilayers was successfully performed
      using molecular dynamics. The DPPC/DPPG/cholesterol bilayer (64 : 64 : 2) was
      used as the lung surfactant phospholipid bilayer model and compared with the DPPC
      bilayer as a reference. Dibenz[a,h]anthracene and its 3,4-diol-1,2-epoxide were
      inserted in water and lipid phases in order to investigate their interactions
      with the lung surfactant phospholipid bilayers. The radial distribution function
      between two P atoms in polar heads shows that the 3,4-diol-1,2-epoxide affects
      the order between the P atoms in the DPPC/DPPG/cholesterol model more than
      dibenz[a,h]anthracene, which is a consequence of its preference for the polar
      heads and dibenz[a,h]anthracene prefers to be located in the hydrocarbon chain of
      the phospholipid bilayers. Dibenz[a,h]anthracene and its 3,4-diol-1,2-epoxide may
      form aggregates in water and lipid phases, and in the water-lipid interface. The
      implications for the possible effect of dibenz[a,h]anthracene and its 3,4-diol
      1,2-epoxide in the lung surfactant phospholipid bilayers are discussed. 

PMID- 26214737
TI  - A self-organized biomechanical network drives shape changes during tissue
      morphogenesis.
AB  - Tissue morphogenesis is orchestrated by cell shape changes. Forces required to
      power these changes are generated by non-muscle myosin II (MyoII) motor proteins
      pulling filamentous actin (F-actin). Actomyosin networks undergo cycles of
      assembly and disassembly (pulses) to cause cell deformations alternating with
      steps of stabilization to result in irreversible shape changes. Although this
      ratchet-like behaviour operates in a variety of contexts, the underlying
      mechanisms remain unclear. Here we investigate the role of MyoII regulation
      through the conserved Rho1-Rok pathway during Drosophila melanogaster germband
      extension. This morphogenetic process is powered by cell intercalation, which
      involves the shrinkage of junctions in the dorsal-ventral axis (vertical
      junctions) followed by junction extension in the anterior-posterior axis. While
      polarized flows of medial-apical MyoII pulses deform vertical junctions, MyoII
      enrichment on these junctions (planar polarity) stabilizes them. We identify two
      critical properties of MyoII dynamics that underlie stability and pulsatility:
      exchange kinetics governed by phosphorylation-dephosphorylation cycles of the
      MyoII regulatory light chain; and advection due to contraction of the motors on F
      actin networks. Spatial control over MyoII exchange kinetics establishes two
      stable regimes of high and low dissociation rates, resulting in MyoII planar
      polarity. Pulsatility emerges at intermediate dissociation rates, enabling
      convergent advection of MyoII and its upstream regulators Rho1 GTP, Rok and MyoII
      phosphatase. Notably, pulsatility is not an outcome of an upstream Rho1
      pacemaker. Rather, it is a self-organized system that involves positive and
      negative biomechanical feedback between MyoII advection and dissociation rates. 

PMID- 26214739
TI  - A Comparison of Gluteus Maximus, Biceps Femoris, and Vastus Lateralis
      Electromyographic Activity in the Back Squat and Barbell Hip Thrust Exercises.
AB  - The back squat and barbell hip thrust are both popular exercises used to target
      the lower body musculature; however, these exercises have yet to be compared.
      Therefore, the purpose of this study was to compare the surface electromyographic
      (EMG) activity of the upper and lower gluteus maximus, biceps femoris, and vastus
      lateralis between the back squat and barbell hip thrust. Thirteen trained women
      (n = 13; age = 28.9 years; height = 164 cm; mass = 58.2 kg) performed estimated
      10-repetition maximums (RM) in the back squat and barbell hip thrust. The barbell
      hip thrust elicited significantly greater mean (69.5% vs 29.4%) and peak (172% vs
      84.9%) upper gluteus maximus, mean (86.8% vs 45.4%) and peak (216% vs 130%) lower
      gluteus maximus, and mean (40.8% vs 14.9%) and peak (86.9% vs 37.5%) biceps
      femoris EMG activity than the back squat. There were no significant differences
      in mean (99.5% vs 110%) or peak (216% vs 244%) vastus lateralis EMG activity. The
      barbell hip thrust activates the gluteus maximus and biceps femoris to a greater
      degree than the back squat when using estimated 10RM loads. Longitudinal training
      studies are needed to determine if this enhanced activation correlates with
      increased strength, hypertrophy, and performance. 

PMID- 26214738
TI  - Regulation of mitochondrial morphology and function by stearoylation of TFR1.
AB  - Mitochondria are involved in a variety of cellular functions, including ATP
      production, amino acid and lipid biogenesis and breakdown, signalling and
      apoptosis. Mitochondrial dysfunction has been linked to neurodegenerative
      diseases, cancer and ageing. Although transcriptional mechanisms that regulate
      mitochondrial abundance are known, comparatively little is known about how
      mitochondrial function is regulated. Here we identify the metabolite stearic acid
      (C18:0) and human transferrin receptor 1 (TFR1; also known as TFRC) as
      mitochondrial regulators. We elucidate a signalling pathway whereby C18:0
      stearoylates TFR1, thereby inhibiting its activation of JNK signalling. This
      leads to reduced ubiquitination of mitofusin via HUWE1, thereby promoting
      mitochondrial fusion and function. We find that animal cells are poised to
      respond to both increases and decreases in C18:0 levels, with increased C18:0
      dietary intake boosting mitochondrial fusion in vivo. Intriguingly, dietary C18:0
      supplementation can counteract the mitochondrial dysfunction caused by genetic
      defects such as loss of the Parkinson's disease genes Pink or Parkin in
      Drosophila. This work identifies the metabolite C18:0 as a signalling molecule
      regulating mitochondrial function in response to diet. 

PMID- 26214740
TI  - The transcription factor TCF-1 initiates the differentiation of T(FH) cells
      during acute viral infection.
AB  - Induction of the transcriptional repressor Bcl-6 in CD4(+) T cells is critical
      for the differentiation of follicular helper T cells (T(FH) cells), which are
      essential for B cell-mediated immunity. In contrast, the transcription factor
      Blimp1 (encoded by Prdm1) inhibits T(FH) differentiation by antagonizing Bcl-6.
      Here we found that the transcription factor TCF-1 was essential for both the
      initiation of T(FH) differentiation and the effector function of differentiated
      T(FH) cells during acute viral infection. Mechanistically, TCF-1 bound directly
      to the Bcl6 promoter and Prdm1 5' regulatory regions, which promoted Bcl-6
      expression but repressed Blimp1 expression. TCF-1-null T(FH) cells upregulated
      genes associated with non-T(FH) cell lineages. Thus, TCF-1 functions as an
      important hub upstream of the Bcl-6-Blimp1 axis to initiate and secure the
      differentiation of T(FH) cells during acute viral infection.

PMID- 26214741
TI  - LEF-1 and TCF-1 orchestrate T(FH) differentiation by regulating differentiation
      circuits upstream of the transcriptional repressor Bcl6.
AB  - Follicular helper T cells (T(FH) cells) are specialized effector CD4(+) T cells
      that help B cells develop germinal centers (GCs) and memory. However, the
      transcription factors that regulate the differentiation of T(FH) cells remain
      incompletely understood. Here we report that selective loss of Lef1 or Tcf7
      (which encode the transcription factor LEF-1 or TCF-1, respectively) resulted in
      T(FH) cell defects, while deletion of both Lef1 and Tcf7 severely impaired the
      differentiation of T(FH) cells and the formation of GCs. Forced expression of LEF
      1 enhanced T(FH) differentiation. LEF-1 and TCF-1 coordinated such
      differentiation by two general mechanisms. First, they established the
      responsiveness of naive CD4(+) T cells to T(FH) cell signals. Second, they
      promoted early T(FH) differentiation via the multipronged approach of sustaining
      expression of the cytokine receptors IL-6Ralpha and gp130, enhancing expression
      of the costimulatory receptor ICOS and promoting expression of the
      transcriptional repressor Bcl6.

PMID- 26214743
TI  - Facile hydrothermal synthesis of NiMoO4@CoMoO4 hierarchical nanospheres for
      supercapacitor applications.
AB  - A novel binder-free electrode material of NiMoO4@CoMoO4 hierarchical nanospheres
      anchored on nickel foam with excellent electrochemical performance has been
      synthesized via a facile hydrothermal strategy. Microstructures and morphologies
      of samples are characterized by X-ray diffraction (XRD), Raman, scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), energy dispersive
      spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). Besides, the
      effect of Ni/Co molar ratios of raw materials on electrochemical behaviors is
      also investigated by cyclic voltammetry, galvanostatic charge-discharge
      measurements, cycling tests and electrochemical impedance spectroscopy methods.
      Remarkably, the resulting NiMoO4@CoMoO4 hierarchical nanospheres with a Ni/Co
      molar ratio of 4 : 1 exhibit greatly enhanced capacitive properties relative to
      other components and display a high specific capacitance of 1601.6 F g(-1) at the
      current density of 2 A g(-1), as well as better cycling stability and rate
      capability. Moreover, a symmetric supercapacitor is constructed using
      NiMoO4@CoMoO4 nanospheres as the positive and negative electrodes with one piece
      of cellulose paper as the separator, which shows good electrochemical
      performance. Such enchanced capacitive properties are mostly attributed to the
      synergistic effect of nickel and cobalt molybdates directly deposited on the
      conductive substrate and their novel hierarchical structure, which can provide
      pathways for fast diffusion and transportation of ions and electrons and a large
      number of active sites. The results imply that the NiMoO4@CoMoO4 hierarchical
      nanospheres could be promising candidates for electrochemical energy storage. 

PMID- 26214742
TI  - The ubiquitin-specific protease USP8 is critical for the development and
      homeostasis of T cells.
AB  - The modification of proteins by ubiquitin has a major role in cells of the immune
      system and is counteracted by various deubiquitinating enzymes (DUBs) with poorly
      defined functions. Here we identified the ubiquitin-specific protease USP8 as a
      regulatory component of the T cell antigen receptor (TCR) signalosome that
      interacted with the adaptor Gads and the regulatory molecule 14-3-3beta. Caspase
      dependent processing of USP8 occurred after stimulation of the TCR. T cell
      specific deletion of USP8 in mice revealed that USP8 was essential for thymocyte
      maturation and upregulation of the gene encoding the cytokine receptor IL-7Ralpha
      mediated by the transcription factor Foxo1. Mice with T cell-specific USP8
      deficiency developed colitis that was promoted by disturbed T cell homeostasis, a
      predominance of CD8(+) gammadelta T cells in the intestine and impaired
      regulatory T cell function. Collectively, our data reveal an unexpected role for
      USP8 as an immunomodulatory DUB in T cells. 

PMID- 26214744
TI  - Computational analysis of pediatric ventricular assist device implantation to
      decrease cerebral particulate embolization.
AB  - Stroke is the most devastating complication after ventricular assist device (VAD)
      implantation with a 19% incidence and 65% mortality in the pediatric population.
      Current pediatric VAD technology and anticoagulation strategies alone are
      suboptimal. VAD implantation assisted by computational methods (CFD) may
      contribute reducing the risk of cerebral embolization. Representative three
      dimensional aortic arch models of an infant and a child were generated. An 8 mm
      VAD outflow-graft (VAD-OG) anastomosed to the aorta was rendered and CFD was
      applied to study blood flow patterns. Particle tracks, originating in the VAD,
      were computed with a Lagrangian phase model and the percentage of particles
      entering the cerebral vessels was calculated. Eight implantation configurations
      (infant = 5 and child = 3) and 5 particle sizes (0.5, 1, 2, 3, and 4 mm) were
      considered. For the infant model, percentage of particles entering the cerebral
      vessels ranged from 15% for a VAD-OG anastomosed at 90 degrees  to the aorta, to
      31% for 30 degrees  VAD-OG anastomosis (overall percentages: X(2) = 10,852, p <
      0.0001). For the child model, cerebral embolization ranged from 9% for the 30
      degrees  VAD-OG anastomosis to 15% for the 60 degrees  anastomosis (overall
      percentages: chi(2) = 10,323, p < 0.0001). Using detailed CFD calculations, we
      demonstrate that the risk of stroke depends significantly on the VAD implantation
      geometry. In turn, the risk probably depends on patient-specific anatomy. CFD can
      be used to optimize VAD implantation geometry to minimize stroke risk.

PMID- 26214746
TI  - Ionic liquid effects on a multistep process. Increased product formation due to
      enhancement of all steps.
AB  - The reaction of a series of substituted benzaldehydes with hexylamine was
      examined in acetonitrile and an ionic liquid. In acetonitrile, as the electron
      withdrawing nature of the substituent increases, the overall addition-elimination
      process becomes faster as does the build-up of the aminol intermediate. Under
      equivalent conditions in an ionic liquid, less intermediate build up is observed,
      and the effect on the rate on varying the substituent is different to that in
      acetonitrile. Extensive kinetic analysis shows that the ionic liquid solvent
      increases the rate constant of all steps of the reaction, resulting in faster
      product formation relative to acetonitrile; these effects increase with the
      proportion of ionic liquid in the reaction mixture. Differences in the
      equilibrium position of the addition step in the ionic liquid were found to
      account for both the decrease in intermediate build up relative to acetonitrile,
      as well as the differing trend in the overall rate of product formation as the
      substituent was changed. The microscopic origins of these ionic liquid effects
      were probed through temperature dependent analyses, highlighting the subtle
      balance of interactions between the ionic liquid and species along the reaction
      coordinate, particularly the importance of charge development in the transition
      state. 

PMID- 26214745
TI  - B Cell Activating Factor (BAFF) and BAFF Receptor Expression in Autoimmune and
      Nonautoimmune Thyroid Diseases.
AB  - BACKGROUND: The B cell activating factor (BAFF) is a member of the tumor necrosis
      factor family, which controls the survival/proliferation of B cells and is
      involved in the pathogenesis of a number of autoimmune diseases. The objective of
      the present study was to investigate the expression of BAFF and BAFF receptor
      (BAFF-R) in the thyroid tissue of patients affected with autoimmune thyroid
      disorders (AITD) or multinodular goiter (MNG) compared with those with normal
      thyroids. METHODS: Immunohistochemistry was performed using a panel of antibodies
      against BAFF, BAFF-R, CD3, CD4, CD8, CD20, CD34, CD79a, CD1a, CD68, and CD163 on
      the thyroid sections of 27 patients affected with Graves' disease (GD), 23 with
      Hashimoto's thyroiditis (HT), 16 with nontoxic nodular goiter (NTG), and 15 with
      toxic nodular goiter (TG), submitted to total thyroidectomy between 2000 and
      2011. RESULTS: The overall BAFF-R expression in thyrocytes was weak and not
      different in AITD and MNG. Conversely, a stronger BAFF expression was observed in
      MNG compared with AITD. BAFF and BAFF-R expression in the infiltrating
      lymphocytes was higher in AITD compared with MNG. Interestingly, in lymphocytes
      of follicular-like structures observed in HT, BAFF and BAFF-R were localized in
      the germinal center or in the mantle, respectively. CONCLUSIONS: This study shows
      that BAFF and BAFF-R are expressed in the thyrocytes derived from patients with
      either AITD or MNG, in addition to the expected expression of BAFF and its
      receptor in the infiltrating immune cells of GD and HT. These findings suggest a
      possible involvement of BAFF and its receptors in the pathophysiology of AITD.

PMID- 26214747
TI  - Acute heart failure in patients with acute aortic syndrome: pathophysiology and
      clinical-prognostic implications.
AB  - AIMS: Although acute heart failure (AHF) is a potential complication of acute
      aortic syndromes (AAS), its clinical details and management implications have
      been scarcely evaluated. This study aimed to assess prevalence,
      pathophysiological mechanisms, impact on treatment, and in-hospital mortality of
      AHF in AAS. METHODS AND RESULTS: Data were collected from a prospective AAS
      registry (398 patients diagnosed between 2000 and 2013). Patients with AHF were
      identified by the presence of dyspnoea as the presentation symptom or
      radiological signs of pulmonary congestion or cardiogenic shock, including
      patients with cardiac tamponade (CT). AHF frequency was 28% (Stanford type A 32%
      vs. type B 20%, P = 0.01). Four mechanisms leading to AHF were identified, alone
      or in combination: CT (26%), aortic regurgitation (25%), myocardial ischaemia
      (17%), and hypertensive crisis (10%). In type A patients, aortic regurgitation
      and CT were the most frequent mechanisms, whereas myocardial ischaemia and
      hypertensive crisis were the most frequent in type B patients. Although no
      difference was noted for diagnostic times, AHF at presentation led to a longer
      surgical delay in type A AAS. In-hospital mortality was higher in patients with
      AHF compared with those without (34% vs. 17%, P < 0.001). After multivariable
      analysis, AHF was associated with increased risk of in-hospital death (adjusted
      odds ratio 1.97, 95% confidence interval 1.14-3.36, P = 0.014). CONCLUSION: AHF
      occurs in more than a quarter of patients with AAS of both type A and type B, is
      due to a variety of pathophysiological mechanisms, and is associated with
      increased surgical delay and in-hospital mortality.

PMID- 26214748
TI  - Bacillus radicibacter sp. nov., a new bacterium isolated from root nodule of
      Oxytropis ochrocephala Bunge.
AB  - A Gram-positive, facultative anaerobic, rod-shaped, and endospore-forming strain,
      designated 53-2(T) was isolated from the root nodule of Oxytropis ochrocephala
      Bunge growing on Qilian mountain, China. The strain can grow at pH 7.0-8.0, 10-50
      degrees C and tolerate up to 11% NaCl. Optimal growth occurred at pH 7.2 and 37 
      degrees C. The result of BLASTn search based on 16S rRNA gene sequence revealed
      that strain 53-2(T) , being closest related to Bacillus acidicola 105-2(T) ,
      possessed remote similarity (less than 95.64%) to the species within genus
      Bacillus. The DNA G + C content was 37.8%. Chemotaxonomic data (major quinone is
      MK-7; major polar lipids are diphosphatidylglycerol, phosphatidylglycerol,
      unknown phospholipid, and aminoglycophospholipid; fatty acids are anteiso-C15: 0
      , iso-C15:0 and anteiso-C17: 0 ) supported the affiliation of the isolate to the
      genus Bacillus. On the basis of physiological, phylogenetic, and biochemical
      properties, strain 53-2(T) represents a novel species within genus Bacillus, for
      which the name Bacillus radicibacter is proposed. The type strain is 53-2(T)
      (=DSM27302(T) =ACCC06115(T) =CCNWQLS5(T) ). 

PMID- 26214749
TI  - Kinetically controlled synthesis of large-scale morphology-tailored silver
      nanostructures at low temperature.
AB  - Ag nanostructures are widely used in catalysis, energy conversion and chemical
      sensing. Morphology-tailored synthesis of Ag nanostructures is critical to tune
      physical and chemical properties. In this study, we develop a method for
      synthesizing the morphology-tailored Ag nanostructures in aqueous solution at a
      low temperature (45  degrees C). With the use of AgCl nanoparticles as the
      precursor, the growth kinetics of Ag nanostructures can be tuned with the pH
      value of solution and the concentration of Pd cubes which catalyze the reaction.
      Ascorbic acid and cetylpyridinium chloride are used as the mild reducing agent
      and capping agent in aqueous solution, respectively. High-yield Ag nanocubes,
      nanowires, right triangular bipyramids/cubes with twinned boundaries, and
      decahedra are successfully produced. Our method opens up a new environmentally
      friendly and economical route to synthesize large-scale and morphology-tailored
      Ag nanostructures, which is significant to the controllable fabrication of Ag
      nanostructures and fundamental understanding of the growth kinetics. 

PMID- 26214750
TI  - Treatment of neonatal fungal infective endocarditis with recombinant tissue
      plasminogen: activator in a low birth weight infant case report and review of the
      literature.
AB  - With advances in medical sciences, an increase in survival rates of low birth
      weight; increased incidence in use of catheter and antibiotics, and total
      parenteral nutrition are reported, therefore, the rate of fungal infections in
      late and very late onset neonatal sepsis have increased. Although fungal
      endocarditis rarely occur in newborns, it has a high morbidity and mortality.
      Antifungal therapy is often insufficient in cases who develop fungal endocarditis
      and surgical treatment is not preferred due to its difficulty and high mortality.
      Herein, fungal endocarditis in a preterm newborn treated with single-dose
      recombinant tissue plasminogen activator in addition to antifungal therapy is
      presented and relevant literature has been reviewed. The vegetation completely
      disappeared following treatment and no complication was observed. 

PMID- 26214751
TI  - Informed Consent and Communicating Risk and Benefits of Research on Higher-Risk
      Medications.

PMID- 26214752
TI  - Acidosis-Induced Changes in Proteome Patterns of the Prostate Cancer-Derived
      Tumor Cell Line AT-1.
AB  - Under various pathological conditions, such as inflammation, ischemia and in
      solid tumors, physiological parameters (local oxygen tension or extracellular pH)
      show distinct tissue abnormalities (hypoxia and acidosis). For tumors, the
      prevailing microenvironment exerts a strong influence on the phenotype with
      respect to proliferation, invasion, and metastasis formation and therefore
      influences prognosis. In this study, we investigate the impact of extracellular
      metabolic acidosis (pH 7.4 versus 6.6) on the proteome patterns of a prostate
      cancer-derived tumor cell type (AT-1) using isobaric labeling and LC-MS/MS
      analysis. In total, 2710 proteins were identified and quantified across four
      biological replicates, of which seven were significantly affected with changes
      >50% and used for validation. Glucose transporter 1 and farnesyl pyrophosphatase
      were found to be down-regulated after 48 h of acidic treatment, and
      metallothionein 2A was reduced after 24 h and returned to control values after 48
      h. After 24 and 48 h at pH 6.6, glutathione S transferase A3 and NAD(P)H
      dehydrogenase 1, cellular retinoic acid-binding protein 2, and Na-bicarbonate
      transporter 3 levels were found to be increased. The changes in protein levels
      were confirmed by transcriptome and functional analyses. In addition to the
      experimental in-depth investigation of proteins with changes >50%, functional
      profiling (statistical enrichment analysis) including proteins with changes >20%
      revealed that acidosis upregulates GSH metabolic processes, citric acid cycle,
      and respiratory electron transport. Metabolism of lipids and cholesterol
      biosynthesis were downregulated. Our data comprise the first comprehensive report
      on acidosis-induced changes in proteome patterns of a tumor cell line. 

PMID- 26214753
TI  - New dammarane and ursane-type triterpenoids from the flower of Ixora coccinea
      Linn.
AB  - Two new esters of dammarane triterpenoids ixorene isovalerate (1), ixorene 3',8'
      dimethyloctanoate (2) and a new ursane-type triterpenoids Ixoroid acid (3) were
      isolated from the methanolic extract of flowers of Ixora coccinea Linn., along
      with the three known constituents. The structures of compounds 1 and 3 were
      elucidated on the basis of extensive 1D,2D NMR studies and mass spectrometry as
      17beta-dammara-12,20-diene-3beta-isovelarate and 3beta-hydroxy-18beta-urs-12ene
      29beta-oic acid, respectively, whereas 2 was identified as 17beta-dammara-12,20
      diene-3beta-3',8'-dimethyloctanoate through (1)H NMR and mass spectral data.
      Compounds 1, 2, 4 and 5 were evaluated for their in vitro cytotoxic activity,
      which exhibited weak activity against the 3T3, PC3 and HeLa cell lines with the
      IC50 value >30 MUM. Antioxidant results of 1 - 5 revealed that only compound 5
      showed antioxidant activity in DPPH radical scavenging inhibition with the IC50
      1.31 * 10(- 6) +/- 0.005 MUm mL(- 1). Both activities are the first records of
      these isolated compounds from the flowers of Ixora coccinea Linn.

PMID- 26214754
TI  - Coordination-Driven Self-Assembly of Carbazole-Based Metallodendrimers with
      Generation-Dependent Aggregation-Induced Emission Behavior.
AB  - A new family of 120 degrees  carbazole-based dendritic donors D1-D3 have been
      successfully designed and synthesized, from which a series of novel
      supramolecular carbazole-based metallodendrimers with well-defined shapes and
      sizes were successfully prepared by [2+2] and [3+3] coordination-driven self
      assembly. The structures of newly designed rhomboidal and hexagonal
      metallodendrimers were characterized by multinuclear NMR ((1) H and (31) P)
      spectroscopy, ESI-TOF mass spectrometry, FTIR spectroscopy, and the PM6
      semiempirical molecular orbital method. The fluorescence emission behavior of
      ligands D1-D3, rhomboidal metallodendrimers R1-R3, and hexagonal
      metallodendrimers H1-H3 in mixtures of dichloromethane and n-hexane with
      different n-hexane fractions were investigated. The results indicated that D1-D3
      featured typical aggregation-induced emission (AIE) properties. However,
      different from ligands D1-D3, metallodendrimers R1-R3 and H1-H3 presented
      interesting generation-dependent AIE properties. Furthermore, evidence for the
      aggregation of these metallodendrimers was confirmed by a detailed investigation
      of dynamic light-scattering, Tyndall effect, and SEM. This research not only
      provides a highly efficient strategy for constructing carbazole-based dendrimers
      with well-defined shapes and sizes, but also presents a new family of carbazole
      based dendritic ligands and rhomboidal and hexagonal metallodendrimers with
      interesting AIE properties. 

PMID- 26214757
TI  - Cytotoxicity, tumor targeting and PET imaging of sub-5 nm KGdF4 multifunctional
      rare earth nanoparticles.
AB  - Ultrasmall sub-5 nm KGdF4 rare earth nanoparticles were synthesized as
      multifunctional probes for fluorescent, magnetic, and radionuclide imaging. The
      cytotoxicity of these nanoparticles in human glioblastoma U87MG and human non
      small cell lung carcinoma H1299 cells was evaluated, and their application for in
      vitro and in vivo tumor targeted imaging has also been demonstrated. 

PMID- 26214755
TI  - Fertility preservation knowledge, counseling, and actions among adolescent and
      young adult patients with cancer: A population-based study.
AB  - BACKGROUND: The fertility of adolescent and young adult (AYA) patients with
      cancer can be threatened by treatments, but to the authors' knowledge little is
      known regarding the extent to which providers discuss this with patients or
      recommend fertility preservation, or the patient and physician characteristics
      associated with these interactions. METHODS: Questionnaires from 459 AYA patients
      with cancer who were diagnosed between 2007 and 2008 and recruited through 7 US
      population-based cancer registries were analyzed using sex-specific multivariable
      models. The authors assessed characteristics associated with not discussing
      therapy effects on fertility or fertility preservation options, and not making
      fertility preservation arrangements. RESULTS: Males without a medical oncologist
      were more likely not to be told that therapy might affect fertility than those
      with a medical oncologist (male odds ratio [OR], 2.28; 95% confidence interval
      [95% CI], 1.03-5.00). Individuals without insurance (male OR, 2.91 [95% CI, 1.41
      5.91] and female OR, 5.46 [95% CI, 1.59-18.72]); those raising children aged <18
      years; and, among males only, those who received treatment posing no or a low
      fertility risk (OR, 3.39; 95% CI, 1.60-7.16) were more likely not to discuss
      fertility preservation with providers. Finally, among males, those without a
      college degree (OR, 1.98; 95% CI, 1.00-3.97), lacking private insurance (OR,
      2.97; 95% CI, 1.16-7.63), and raising children aged <18 years (OR, 3.53; 95% CI,
      1.63-7.65) were more likely to not make fertility preservation arrangements; too
      few females had made fertility preservation arrangements for similar analyses to
      be performed. CONCLUSIONS: Discussion and action surrounding fertility
      preservation for AYA patients with cancer are associated with medical factors,
      patient socioeconomic data, and child-rearing status. These results highlight the
      need for insurance coverage for fertility preservation and increased awareness of
      fertility preservation options.

PMID- 26214758
TI  - An ultra-microporous organic polymer for high performance carbon dioxide capture
      and separation.
AB  - Rational design concepts were used to prepare a novel porous benzimidazole-linked
      polymer (BILP-101) in a simple one-pot reaction. BILP-101 has exhibited ultra
      microporosity (0.54 nm), very high CO2 uptake (~1 mmol g(-1), 4 wt%, 0.15 bar/298
      K) and exceptional CO2/N2 selectivity of 80 (298 K), which results in remarkable
      working capacity and regenerability for CO2 capture applications. 

PMID- 26214756
TI  - Pathologic Manifestations on Surgical Biopsy and Their Correlation with Clinical
      Indices in Dogs with Degenerative Mitral Valve Disease.
AB  - BACKGROUND: Evaluation of myocardial function is clinically challenging in dogs
      with degenerative mitral valve disease (DMVD). Although myocardial dysfunction is
      caused by pathologic degeneration, histopathologic progression is poorly
      understood. OBJECTIVES: To characterize myocardial and pulmonary pathologic
      changes according to severity in dogs with naturally occurring DMVD, and to
      investigate whether or not pathologic degeneration is reflected by traditional
      clinical indices. ANIMALS: One hundred and seventeen dogs with naturally
      occurring DMVD. METHODS: Prospective observational study. Biopsied left atrium
      (LA), left ventricle (LV), and lung were evaluated histologically, and an attempt
      was made to correlate pathologic findings with clinical indices. RESULTS: Severe
      myocardial changes were observed in all International Small Animal Cardiac Health
      Council classes. In the lung, heart failure cell levels were significantly
      increased in class III patients (P < .0001). In a paired comparison, the LA
      showed significantly more severe degeneration than the LV, including myocardial
      fatty replacement, immune cell infiltration, and interstitial fibrosis (P <
      .0001). In contrast, myocardial cells were more hypertrophied in the LV than in
      the LA (P < .0001). Left ventricular end-diastolic dimension (LVEDd) was
      associated with fatty replacement (P = .033, R(2) = 0.584) and myocardial
      vacuolization (P = .003, R(2) = 0.588) in the LA. CONCLUSIONS AND CLINICAL
      IMPORTANCE: In DMVD, although severe pathologic changes may be evident even in
      early stages, there may be pathologic discrepancy between the LA and the LV.
      Myocardial degeneration may be reflected by clinical indices such as LVEDd and
      EF.

PMID- 26214759
TI  - The ferroelectric polarization of Y2CoMnO6 aligns along the b-axis: the first
      principles calculations.
AB  - Double-perovskite A2BB'O6 oxides with magnetic B and B' ions and E*-type
      antiferromagnetic order (E*-AFM, i.e. the ???? structure) are believed to exhibit
      promising multiferroic properties, and Y2CoMnO6 (YCMO) is one candidate in this
      category. However, the microscopic origins for magnetically induced
      ferroelectricity in YCMO remain unclear. In this study, we perform detailed
      symmetry analysis on the exchange striction effect and lattice distortion, plus
      the first-principles calculations on YCMO. The E*-AFM state as the ground state
      with other competing states such as ferromagnetic and A-antiferromagnetic orders
      is confirmed. It is observed that the ferroelectricity is generated by the
      exchange striction associated with the E*-AFM order and chemically ordered Mn/Co
      occupation. Both the lattice symmetry consideration and first-principles
      calculations predict that the electric polarization aligns along the b-axis. The
      calculated polarization reaches up to 0.4682 MUC cm(-2), mainly from the ionic
      displacement contribution. The present study presents a comprehensive
      understanding of the multiferroic mechanisms in YCMO and is of general
      significance for predicting emergent multiferroicity in other double-perovskite
      magnetic oxides. 

PMID- 26214760
TI  - Heritability and genetic correlations of personality traits in a wild population
      of yellow-bellied marmots (Marmota flaviventris).
AB  - Describing and quantifying animal personality is now an integral part of
      behavioural studies because individually distinctive behaviours have ecological
      and evolutionary consequences. Yet, to fully understand how personality traits
      may respond to selection, one must understand the underlying heritability and
      genetic correlations between traits. Previous studies have reported a moderate
      degree of heritability of personality traits, but few of these studies have
      either been conducted in the wild or estimated the genetic correlations between
      personality traits. Estimating the additive genetic variance and covariance in
      the wild is crucial to understand the evolutionary potential of behavioural
      traits. Enhanced environmental variation could reduce heritability and genetic
      correlations, thus leading to different evolutionary predictions. We estimated
      the additive genetic variance and covariance of docility in the trap, sociability
      (mirror image stimulation), and exploration and activity in two different
      contexts (open-field and mirror image simulation experiments) in a wild
      population of yellow-bellied marmots (Marmota flaviventris). We estimated both
      heritability of behaviours and of personality traits and found nonzero additive
      genetic variance in these traits. We also found nonzero maternal, permanent
      environment and year effects. Finally, we found four phenotypic correlations
      between traits, and one positive genetic correlation between activity in the open
      field test and sociability. We also found permanent environment correlations
      between activity in both tests and docility and exploration in the MIS test. This
      is one of a handful of studies to adopt a quantitative genetic approach to
      explain variation in personality traits in the wild and, thus, provides important
      insights into the potential variance available for selection. 

PMID- 26214761
TI  - Micelles of d-alpha-Tocopheryl Polyethylene Glycol 2000 Succinate (TPGS 2K) for
      Doxorubicin Delivery with Reversal of Multidrug Resistance.
AB  - The purpose of this study is to investigate the ability of doxorubicin (DOX)
      loaded d-alpha-tocopheryl polyethylene glycol 2000 succinate (TPGS 2K) micelles
      to overcome MDR in breast cancer treatment. The DOX-loaded TPGS 2K micelles
      exhibited an average size of around 23 nm, a near neutral zeta potential of
      around 4 mv and high encapsulation efficiency (85.22 +/- 1.89%). The TPGS 2K
      conjugate did not have significant influences on the reduction of mitochondrial
      membrane potential (MMP) and the depletion of intracellular ATP level of MCF
      7/ADR cells but had an evident effect on the inhibition of Verapamil-induced P-gp
      ATPase activity. In vitro cell culture experiments demonstrated the DOX-loaded
      TPGS 2K micelles, resulting in higher cellular uptake and more significant
      cytotoxicity effect against MCF-7/MDR cells than the free DOX solution.
      Additionally, the in vivo imaging study revealed DiR-loaded TPGS 2K micelles
      distributed selectively in MCF-7/ADR tumor-bearing nude mice and had a sufficient
      residence time. In the anticancer efficacy test with MCF-7/ADR tumor bearing nude
      mice, the DOX-loaded TPGS 2K micelles displayed significantly higher antitumor
      activity compared with free DOX solution at the same DOX dosage but less toxicity
      evaluated by the change of body weight and histological examination. Therefore,
      this drug delivery micellar system based on TPGS 2K conjugates can serve as a
      potential nanomedicine for reversing MDR. 

PMID- 26214763
TI  - Niacin supplement in schizophrenia: Hit two birds with one stone.

PMID- 26214762
TI  - Pollen-derived nonallergenic substances enhance Th2-induced IgE production in B
      cells.
AB  - BACKGROUND: B cells play a central role in IgE-mediated allergies. In damaged
      airway epithelium, they are exposed directly to aeroallergens. We aimed to assess
      whether direct exposure of B cells to pollen constituents affects allergic
      sensitization. METHODS: B cells from murine splenocytes and from blood samples of
      healthy donors were incubated for 8 days under Th2-like conditions with aqueous
      ragweed pollen extracts (Amb-APE) or its constituents. Secreted total IgM, IgG,
      and IgE was quantified by ELISA. Additionally, birch, grass, or pine-pollen
      extracts were tested. The number of viable cells was evaluated by ATP
      measurements. B-cell proliferation was measured by CFSE staining. IgE class
      switch was analyzed by quantitation of class switch transcripts. In an OVA/Alum
      i.p.-sensitization mouse model, Amb-APE was intranasally instilled for 11
      consecutive days. RESULTS: Upon Th2 priming of murine B cells, ragweed pollen
      extract caused a dose-dependent increase in IgE production, while IgG and IgM
      were not affected. The low-molecular-weight fraction and phytoprostane E1 (PPE1)
      increased IgE production, while Amb a 1 did not. PPE1 enhanced IgE also in human
      memory B cells. Under Th1 conditions, Amb-APE did not influence immunoglobulin
      secretion. The IgE elevation was not ragweed specific. It correlated with
      proliferation of viable B cells, but not with IgE class switch. In vivo, Amb-APE
      increased total IgE and showed adjuvant activity in allergic airway inflammation.
      CONCLUSIONS: Aqueous pollen extracts, the protein-free fraction of Amb-APE, and
      the pollen-contained substance PPE1 specifically enhance IgE production in Th2
      primed B cells. Thus, pollen-derived nonallergenic substances might be
      responsible for B-cell-dependent aggravation of IgE-mediated allergies.

PMID- 26214764
TI  - Correlation does not imply causation.

PMID- 26214765
TI  - Concha bullosa related headache disability.
AB  - OBJECTIVE: Rhinogenic headache (RH) is a headache or facial pain syndrome
      secondary to mucosal contact points in the sino-nasal cavities, in the absence of
      inflammatory signs, hyperplastic mucosa, purulent discharge, sino-nasal polyps or
      masses. It may result from pressure on the nasal mucosa due to anatomical
      variations among which the pneumatization of the middle turbinate, concha
      bullosa, a variant of the development of ethmoidal cells, is the most commonly
      observed. Clinical practice suggests a close correlation between concha bullosa,
      mucosal contacts and rhinogenic headache, with high impact on the QoL. However
      diagnostic and therapeutic difficulties still remain. Aim of the present study is
      to evaluate the impact of medical or surgical care on the QoL of patients
      suffering from concha bullosa related headache from the patients' perspective.
      PATIENTS AND METHODS: One-hundred-two subjects with concha bullosa and headache
      anamnesis were randomized into two groups and given medical or surgical
      treatment. To assess the Quality of life (QoL) we used visual analogue scale and
      for the first time, the migraine disability score before and after treatment.
      RESULTS: After treatment the severity of the headache decreased as well as the
      discomfort in the surgical group compared with medical group. CONCLUSIONS: The
      improvement of symptoms and QoL suggests that the endoscopic surgical plastic may
      promote the rapid resolution of concha bullosa related headache improving the and
      reducing health care costs.

PMID- 26214766
TI  - Granulomatosis with polyangiitis in pregnancy - clinical implications and
      treatment possibilities.
AB  - Granulomatosis with polyangiitis (GPA) is an autoimmune disease which has a
      variable clinical presentation and usually progresses from a localized to a
      generalized form over the course of weeks to years. Histopathologically, it is a
      necrotizing systematic vasculitis that can cause sino-nasal, pulmonary, renal,
      ocular, and cutaneous manifestations. Diagnostic workup should include serologic,
      radiologic, endoscopic and histopathological examination. Autoantibody c-ANCA may
      be used as a marker of disease activity and individual follow-up. An appropriate
      local and systemic treatment should be implemented, which is particularly
      important in pregnancy. Comprehensive management should be planned, including the
      needs of both mother and fetus (particularly if vasculitis is diagnosed de novo
      during pregnancy). Pregnancy in patients with GPA is burdened with the risk of
      possible complications and increased mortality and the conception should be
      delayed until remission of the disease. A flare-up of GPA may be life threatening
      for both mother and fetus. The immunosuppressants, which are used during
      pregnancy include glucocorticosteroids (GCS) and azathioprine. Studies of GPA in
      pregnancy are scarce, and this calls for individualized management. Thus, the
      approach to care for pregnant women with GPA is interdisciplinary, and firmly
      places the rheumatologist, gynecologist, pulmonologist, otorhinolaryngologist and
      nephrologist on the management team. 

PMID- 26214767
TI  - Retrospective evaluation of risk factors and perinatal outcome of umbilical cord
      prolapse during labor.
AB  - OBJECTIVE: Umbilical cord prolapse has a reported prevalence of 0.1-0.6%. In
      previous studies, risk factors for umbilical prolapse have been identified as
      multiparity, preterm delivery, non-vertex presentation, and obstetric
      manipulation for labor induction. In the present study, we aimed to investigate
      the risk factors for umbilical cord prolapse and to determine the factors that
      may relate to neonatal morbidity in these patients. PATIENTS AND METHODS: This
      study consisted of recorded cases of umbilical cord prolapse at Dr Zekai Tahir
      Burak Research and Training Hospital between January 2008 and May 2013. Clinical
      and demographic data were obtained by reviewing the patients' medical records.
      Student's t test was performed for parametric variables between groups, and a Chi
      square test was performed for nonparametric variables between groups. A logistic
      regression was performed to investigate the effects of clinical parameters such
      as gestational age, diagnosis to delivery interval, and fetal presentation on
      neonatal morbidity. RESULTS: The patients with umbilical cord prolapse during
      labor had higher rates of preterm deliveries, low-birth-weight infants, and non
      vertex presentations than the control group did. Preterm delivery, non-vertex
      presentation, presence of polyhydramnios, and spontaneous membrane rupture
      increased the risk of umbilical cord prolapse significantly. In the regression
      analysis, gestational age and diagnosis to delivery interval greater than 10
      minutes predicted adverse neonatal outcomes independently. CONCLUSIONS: Umbilical
      cord prolapse is more common in cases of preterm delivery, non-vertex fetal
      presentation, and spontaneous rupture of membranes. A diagnosis to delivery
      interval greater than ten minutes is independently associated with an adverse
      neonatal outcome.

PMID- 26214768
TI  - External cephalic version for singleton breech presentation: proposal of a
      practical check-list for obstetricians.
AB  - OBJECTIVE: External cephalic version (ECV) for breech presentation is not
      routinely performed by obstetricians in many clinical settings. The aim of this
      work is to assess to what extent the factors involved in performing ECV are
      relevant for the success and safety of ECV, in order to propose a practical check
      list for assessing the feasibility of ECV. METHODS: Review of 214 references.
      Factors involved in the success and risks of ECV (feasibility of ECV) were
      extracted and were scored in a semi-quantitative way according to textual
      information, type of publication, year of publication, number of cases. Simple
      conjoint analysis was used to describe the relevance found for each factor.
      RESULTS: Parity has the pivotal role in ECV feasibility (relevance 16.6%),
      followed by tocolysis (10.8%), gestational age (10.6%), amniotic fluid volume
      (4.7%), breech variety (1.9%), and placenta location (1.7%). Other factors with
      estimated relevance around 0 (regional anesthesia, station, estimated fetal
      weight, fetal position, obesity/BMI, fetal birth weight, duration of
      manoeuvre/number of attempts) have some role in the feasibility of ECV. Yet other
      factors, with negative values of estimated relevance, have even less importance.
      CONCLUSIONS: From a logical interpretation of the relevance of each factor
      assessed, ECV should be proposed with utmost prudence if a stringent check-list
      is followed. Such a check-list should take into account: parity, tocolytic
      therapy, gestational age, amniotic fluid volume, breech variety, placenta
      location, regional anesthesia, breech engagement, fetal well-being, uterine
      relaxation, fetal size, fetal position, fetal head grasping capability and fetal
      turning capability.

PMID- 26214769
TI  - The correlation analysis of human embryonic MMP-9 secretion and embryo quality.
AB  - OBJECTIVE: The correlation of the embryo matrix metalloproteinase-9 (MMP-9)
      secretion, embryonic development and clinical pregnancy was investigated.
      MATERIALS AND METHODS: The embryo culture from in vitro fertilization-embryo
      transfer (IVF-ET) patients were collected in the Xuzhou Central Hospital from
      January 2013 to September 2014. At the same time, the embryo grade was recorded.
      The secretion of the MMP-9 in the embryo culture was detected through
      hybridization (Dot-blot) and enzyme-linked immunosorbent assay (ELISA). The
      clinical pregnancy outcome was followed after one month of the embryo transfer.
      RESULTS: With the embryonic development from 2-cell to 8-cell, embryonic MMP-9
      secretion increased gradually (p < 0.05). Though 8/I embryo, the secretion of MMP
      9 are not identical. The quantitative detection of the MMP-9 secretion of the 8
      cell embryo by ELISA is higher as is the embryo score, but the low secretion of
      embryo score is lower (p < 0.001). As 8/I embryos, the clinical pregnancy rate
      (77.3%) of the MMP-9 high secretion embryos is higher than the low secretion
      embryos (16.7%) (p < 0.001). CONCLUSIONS: The secretion of the embryonic MMP-9 is
      closely related to the quality of the embryo and embryo implantation. It is
      speculated that MMP-9 may become one of the criteria to evaluate the quality of
      the embryos.

PMID- 26214770
TI  - Chest and breast MRI: the added value of a fast imaging for a new diagnostic
      approach in the planning of augmentation surgery in patients with thoracic
      asymmetries.
AB  - OBJECTIVE: In breast augmentation surgery, breast symmetry depends on the breast
      tissue, implants and chest wall. Any asymmetry of the anterior thoracic wall can
      influence the breast shape. If breast asymmetry is detected in the preoperative
      evaluation, a chest wall deformity should be suspected. Until now, very few
      reports describe the use of MRI to objectively assess breast and chest
      measurements with the aim of providing customized augmentation. This study
      describes the use of MRI to evaluate breast and chest wall asymmetry, and
      considers the feasibility of preoperative measurements which are useful for
      performing an objective preoperative evaluation. PATIENTS AND METHODS: Between
      April 2012 and February 2013, 13 patients underwent chest/breast MRI scan. Scans
      were performed on a 1.5 T scanner using a single T1 FSE non-suppressed axial
      sequence, without contrast administration. Acquisitions included the breast and
      chest wall. Specific measurements were obtained to assess the overall shape of
      the chest wall and breast, as well as any asymmetry. RESULTS: All patients showed
      some degree of left-right side asymmetry on specific thoracic, breast and implant
      measurements. MRI provided detailed and objective data. CONCLUSIONS: Preliminary
      findings revealed the value of breast/chest wall MRI in the planning of
      augmentation surgery. MRI is a valuable technique in young women because there is
      no use of ionizing radiation. Scans allow surgeons to determine the best surgical
      approach and obtain reproducible and better aesthetic results.

PMID- 26214771
TI  - Mesenchymal stem cells ameliorate LPS-induced acute lung injury through KGF
      promoting alveolar fluid clearance of alveolar type II cells.
AB  - OBJECTIVE: It has been shown that Mesenchymal stem cells (MSCs) could prevent or
      alleviate acute lung injury (ALI) when transplanted into lung; however, the
      mechanisms involved remains elusive. The study aimed to investigate the effect of
      MSCs in repairing alveolar fluid clearance (AFC) of alveolar type-II (AT-II)
      cells through paracrine factors. MATERIALS AND METHODS: Keratinocyte growth
      factor (KGF) concentration in the supernatant of MSC culture medium was measured,
      and MSCs in lung after intravenous administration was traced. Next, MSCs
      transfected with or without KGF SiRNA were injected intravenously into LPS
      induced ALI rats. Histological change and wet/dry ratio were determined. AT-II
      cells were co-cultured with MSCs under different experimental situations to
      analyze the variation of alpha1 and beta1 subunits of Na+-K+-ATPase in AT-II
      cells. RESULTS: LPS-induced ALI was characterized by the typical inflammatory
      infiltrates, interalveolar septal thickening and increased wet/dry ratio. MSC
      administration significantly reduced the injury, while MSCs with KGF knockdown
      did no show the same effect. In vitro study also confirmed that expressions of
      alpha1 and beta1 subunit were up-regulated as impaired AT-II cells co-cultured
      with MSCs. Furthermore, expression of alpha1 subunit was down-regulated, while
      beta1 subunit showed no apparent change as AT-II cells were co-cultured with MSCs
      that were transfected with KGF siRNA. CONCLUSIONS: AFC was impaired by
      inflammation insult. MSCs-derived KGF reduced the impaired AFC through up
      regulated alpha1 subunit but not beta1 subunit, which might provide a novel
      therapeutic strategy for ALI.

PMID- 26214772
TI  - Efficacy of standard dose rituximab for refractory idiopathic thrombocytopenic
      purpura in children.
AB  - OBJECTIVE: The present study intends to investigate the efficacy and safety of
      standard dose rituximab for treatment of refractory idiopathic thrombocytopenic
      purpura (RITP) in children. PATIENTS AND METHODS: A total of 50 cases of children
      hospitalized with RITP in a hospital were enrolled in this study, and randomly
      divided into two treatment groups according to the therapeutic methods: rituximab
      group (n = 26) and vincristine group (n = 24). Another 20 healthy children
      receiving physical examination in the hospital during the corresponding period
      were enrolled as the control group. Before treatment the thrombocytes were
      counted with hematology analyzer and the CD19+/CD20+ B cells in peripheral blood
      tested with flow cytometry in rituximab group. Then the children in the rituximab
      group were given standard dose rituximab at 375 mg/m2 via four weekly intravenous
      drip, while those in vincristine group treated with vincristine at 0.02 mg/kg by
      intravenous drip once a week for three months. During the treatment the adverse
      drug reactions were observed and recorded. After the treatment, the efficacy of
      two drugs was each evaluated, and the thrombocytes and CD19+/CD20+ B cells in
      peripheral blood of rituximab group were quantified in the same way, and the
      children in both treatment groups were followed up and the recurrence rate
      recorded. RESULTS: The total efficiency including complete response and partial
      response in rituximab group was significantly higher than that in vincristine
      group (69.2% vs. 37.5%, chi2 = 9.74, p < 0.01). The prevalence rates of adverse
      reactions were statistically indifferent between two treatment groups during the
      therapy (11.5% vs. 8.3%, chi2 = 0.62, p > 0.05). The follow-up visit showed that
      the recurrence rate of rituximab group including those showing complete response
      and partial response was significantly lower than that of vincristine group
      (22.2% vs. 55.6%, chi2 = 7.24, p < 0.05). The peripheral blood platelet number of
      children showing complete response and partial response in group of rituximab was
      106.7 +/- 32.5 * 109/L after treatment and significantly higher compared with
      that before treatment (t = 12.48, p < 0.01). The amount of CD19+/CD20+ B cells in
      peripheral blood of rituximab group after treatment was significantly lower than
      that before treatment (t = 6.71, p > 0.05). CONCLUSIONS: Rituximab may play a
      role in the efficacy by depleting B cells and can cure RITP in children without
      causing serious adverse reactions.

PMID- 26214773
TI  - The expression of miR-181a-5p and miR-371b-5p in chondrosarcoma.
AB  - OBJECTIVE: Chondrosarcomas are malignant tumors of chondrocytes that affect bones
      and joints, and it represents the third most common type of primary bone tumors.
      Chondrosarcoma is difficult to treat because it is relatively resistant to both
      chemotherapy and radiation. Thus, surgery remains the best available treatment.
      It is important to find new diagnostic markers and improve treatment options.
      BACKGROUND: miRNAs are small non-coding transcripts (19-25 nucleotides) that
      regulate gene expression via targeting complementary sequences within messenger
      RNAs (mRNAs). miRNAs have been shown to be involved in regulation of many
      biochemical pathways. Dysregulated expression of many miRNAs has also been
      associated with multiple human diseases, such as cancer. PATIENTS AND METHODS: 18
      surgical chondrosarcoma specimens were obtained from patients. RNA extractions
      were performed from decalcified paraffin embedded tissues. The aim of this study
      was to investigate the expression levels of miR-181a and miR-371b in patients
      with chondrosarcoma by using RT-PCR and to evaluate the relationship between
      these miRNAs and chondrosarcoma. RESULTS: miR-181a was found to be upregulated in
      chondrosarcoma specimens whereas no significant alteration was found for miR-371b
      expression. CONCLUSIONS: It has been proposed that miRNA expression studies might
      be used as diagnostic, prognostic marker in cancer. miRNA expression data
      produced in our study may contribute future chondrosarcoma diagnosis and therapy.

PMID- 26214774
TI  - Knockdown of CD24 inhibits proliferation, invasion and sensitizes breast cancer
      MCF-7 cells to tamoxifen in vitro.
AB  - OBJECTIVE: CD24 is overexpressed in breast cancer, and patients with high CD24
      expression was resistant to tamoxifen treatment. Furthermore, treatment with CD24
      antibody to inhibit CD24 expression could induce apoptosis and inhibits migration
      in breast cancer cells in vitro. In this study, we investigated the anti-tumor
      efficacy of CD24 knockdown using siRNA targeting CD24 on proliferation, invasion
      and sensitivity to tamoxifen (TAM) of breast cancer MCF-7 cells in vitro.
      MATERIALS AND METHODS: CD24 siRNA vector (CD24-siRNA) and empty plasmid vector
      (EP) were transiently transfected into the breast cancer MCF-7 cells and the
      knockdown efficacy was assessed by Western blot analysis. The effects of CD24
      knockdown on cell viability, apoptosis and sensitivity to TAM in MCF-7 cells were
      determined using methyl thiazolyl blue tetrazolium bromide (MTT), ELISA and
      terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) assays.
      The effects of CD24 knockdown on cell invasion and migration were determined
      using chemoinvasion assay and wound scratch assay, respectively. RESULTS:
      Transfection of CD24-siRNA effectively down-regulated CD24 expression in MCF-7
      cells in vitro. CD24 suppressed showed significantly decreased proliferation,
      invasion and increased apoptosis as well as increased sensitivity to TAM in vitro
      in MCF-7 cells. CONCLUSIONS: Knockdown of CD24 expression by CD24-siRNA
      significantly inhibited invasion and cell viability, and induced apoptosis and
      increased sensitivity of MCF-7 cells to TAM, indicating that knockdown of CD24 by
      siRNA might be a potential therapeutic approach against human breast cancer.

PMID- 26214775
TI  - Analysis of the treatment of gliomas with SEC therapy combined with
      radiochemotherapy.
AB  - OBJECTIVE: To investigate the anti-glioma effects of staphylococcal enterotoxin C
      (SEC) combined with surgery, radiotherapy and chemotherapy, and the IL-2 of
      lymphocytes activated by SEC. PATIENTS AND METHODS: A total of 92 patients with
      gliomas which had been surgically removed, were randomly divided into a control,
      and treatment groups A (systemic application of SEC) and B (local application of
      lymphocytes activated by SEC). The treatment effects were observed on a CT scan
      of the head. The SEC's induction on the IL-2 secretion by lymphocytes was
      determined using immunohistochemistry and RT-PCR methods. RESULTS: Clinical
      materials showed that the effective rate (CR and PR) in the control group was
      32.0%. In the treatment group A, the effective rate was 51.6% and 63.6% in the
      group B. The IL-2 of lymphocytes secreting activity activated by SEC began to
      secrete IL-2 on the 1st day and reached a peak during the 3rd day and the 5th
      day. CONCLUSIONS: As a superantigen, SEC combined with surgery, radiotherapy and
      chemotherapy can improve treatment. The lymphocytes activated by SEC can release
      IL-2.

PMID- 26214776
TI  - Olanzapine inhibits the proliferation and induces the differentiation of glioma
      stem-like cells through modulating the Wnt signaling pathway in vitro.
AB  - OBJECTIVE: Olanzapine, a D2/5-HT2 antagonist, is often used as an atypical
      antipsychotic drug in clinical. Previous research has found its new
      pharmacological influence on enhancing the differentiation of neural stem cells
      (NSCs) to oligodendrocyte-like cells (ODLCs). Glioblastomas are associated with
      poor prognoses owing to the glioma stem-like cells (GSLCs), which have a great
      many of similarities with adult NSCs. Hence, in this article, we aim to study the
      effects and associated mechanisms of olanzapine on GSLCs derived from human U87MG
      glioblastoma cell lines. MATERIALS AND METHODS: The methyl thiazolyl tetrazolium
      (MTT) colorimetric assay was conducted to investigate the effects of olanzapine
      on cell viability of GSLCs. Flow cytometric analysis was applied to study the
      cell cycle dynamics of GSLCs and Cell Counting Kit-8 (CCK-8) was used to further
      investigate the proliferation of GSLCs after treated with olanzapine or dimethyl
      sulfoxide (DMSO) for 48 h. Cell differentiation assay was carried out to study
      the differentiation of GSLCs and then Image-Pro Plus image analysis was used to
      measure the protrusion length of the differentiated cells. Furthermore, the
      confocal [Ca2+]c measurement was conducted to observe the influence of olanzapine
      on the opening function of Ca2+ channel. After the application of olanzapine for
      48 h, RT-PCR was conducted to measure mRNA levels of calcium-sensing receptor
      (CaSR) and stromal interaction molecule 1 (STIM1), and Western blotting analysis
      was carried out to examine the expression of myelin basic protein (MBP), glial
      fibrillary acidic protein (GFAP), CaSR protein, STIM1 protein and beta-catenin
      protein. RESULTS: Our results demonstrated that olanzapine inhibited the
      proliferation of GSLCs by arresting cell cycle in G0/G1 phase and facilitated the
      differentiation of such cells to ODLCs. After treated with olanzapine for 48 h,
      cells were very sensitive to 100 mM K+ stimulation, with increased spontaneous
      calcium wave. We also found olanzapine increased the protein expression of MBP
      and GFAP. In addition, the mRNA transcription and protein expression of CaSR and
      STIM1 were enhanced after treated with olanzapine for 48h, while the protein
      expression of beta-catenin was suppressed. CONCLUSIONS: Our results suggest that
      olanzapine modulates the Wnt signaling pathway through activating the Ca2+
      pathway and restraining the beta-catenin pathway, leading to the differentiation
      of GSLCs to ODLCs. It provides exciting prospects that olanzapine might be a new
      novel chemotherapeutic modality targeting GSLCs for the treatment of
      glioblastomas.

PMID- 26214777
TI  - Role of Delta133p53 in Tumor Necrosis Factor-induced survival of p53 functions in
      MKN45 gastric cancer cell line.
AB  - OBJECTIVE: To explore the role of Delta133p53 in the effect of recombinant mutant
      human Tumor Necrosis Factor (rmhTNF) on two gastric cancer cell lines. MATERIALS
      AND METHODS: MKN45 (with Delta133p53 expression) or SGC7901 (without Delta133p53
      expression) cells were treated with rmhTNF of different concentrations only or
      combined with fluorouracil (5-FU), and the growth inhibition rate was detected by
      a cell counting kit, and apoptosis by flow cytometry. The mRNA of Delta133p53,
      p53, Gadd45alpha, MDM2, PTEN and Bax was measured by reverse transcription PCR
      (RT-PCR) or Nested PCR (nPCR). RESULTS: On Delta133p53-positive MKN-45 cells, the
      effect of rmhTNF was significant in growth inhibition test (t = -9.558, p <
      0.01); also, the effect of 5-FU was improved by rmhTNF with remarkable time- and
      dose-effect (F = 82.742, p < 0.01; F = 128.583, p < 0.01). However, on
      Delta133p53-negative SGC-7901 cells, no growth inhibition was showed by rmhTNF
      only (t = -0.121, p > 0.05). In apoptosis test, the effect of rmhTNF was
      significant on MKN45 cells, and the effect of 5-FU was improved significantly by
      rmhTNF (F = 123.931, p < 0.05). In mRNA measurement, rmhTNF-induced up-regulation
      of p53 accompanied with down-regulation of Delta133p53, which correlated
      significantly to the change of p53 downstream molecules, including MDM2, PTEN,
      Gadd45alpha, and Bax. CONCLUSIONS: The results in these experiments suggested
      that Delta133p53 play a pivotal role in rmhTNF-induced survival of p53 functions
      in Delta133p53-positive MKN-45 cells.

PMID- 26214778
TI  - Integrated regulatory network involving differently expressed genes and protein
      protein interaction on pancreatic cancer.
AB  - OBJECTIVE: Pancreatic cancer is a deadly disease with poor prognosis. However,
      comprehensive understanding about its pathogenesis remains insufficient. In this
      study, we aimed to find potential novel approaches for the treatment of
      pancreatic cancer and explore the regulatory mechanisms underlying pancreatic
      cancer progression. MATERIALS AND METHODS: The gene expression profile data
      GSE32688 were downloaded from Gene Expression Omnibus database followed by
      background correction and normalization through GCRMA (GC Robust Multi-array
      Average) method. Then DEGs (differentially expressed genes) were identified using
      t-test method and DEGs-related PPIs (protein-protein interaction) were extracted
      from STRING database. The PPI networks were constructed by calculating the
      pearson correlation coefficient under different conditions. Moreover, the network
      was divided into a number of unit modules, and KEGG pathway and GO analysis were
      performed for genes in module networks using clusterProfiler. RESULTS: In total,
      199 DEGs (165 up-regulated genes and 34 down-regulated genes) were screened
      between tumor and normal samples. The integrated DEG. PPI network was established
      by comparing two different networks under tumor and normal conditions
      respectively. The top ten genes with high degrees such as ANLN, PSRC1 and ECT2
      were identified in the integrated network, and they were mainly enriched in cell
      cycle pathway. CONCLUSIONS: ECT2 and PSRC1 might be used as two novel biomarkers
      for diagnosis and management of pancreatic cancer.

PMID- 26214779
TI  - Chest imaging comparison between non-tuberculous and tuberculosis mycobacteria in
      sputum acid fast bacilli smear-positive patients.
AB  - OBJECTIVE: The aim of this study was to distinguish and compare the chest imaging
      features of non-tuberculous mycobacteria lung disease (NTM-LD) and pulmonary
      tuberculosis (PTB) in patients with sputum acid fast bacillus (AFB)-smear
      positive since an earlier differential diagnosis between these two is very
      important in clinical practice. PATIENTS AND METHODS: A total of 4167 previously
      untreated cases with AFB smear-positive sputum were collected from January 2011
      to January 2014, in Shanghai Pulmonary Hospital, Tongji University, China. Among
      them, 124 cases were identified with NTM-LD after specimen culture and strain
      identification. A cohort of 210 patients with PTB was randomly selected from the
      remaining 4043 cases with PTB as comparator. The clinical and chest computed
      tomography (CT) imaging data were compared. RESULTS: The most prevalent pathogens
      in patients with NTM-LD were Mycobacterium abscessus (42%, 52/124) and
      Mycobacterium intracellulare (34%, 42/124). Univariate analysis showed patients
      with NTM-LD more frequently had bronchiectasis (85.5% vs. 45.7%, p < 0.001), thin
      walled cavity (D >= 3 cm) (16.9% vs. 7.6%, p = 0.011) compared to PTB patients.
      Additionally, the location of lesion also differed and the right middle lobe
      (23.9% vs. 16.3%, p < 0.001) and left lingual segment bronchiectasis (19.9% vs.
      8.2%, p < 0.001) were more prominent in NTM-LD. Multivariate analysis showed,
      bronchiectasis (OR = 8.521, 95% CI: 4.209-17.250, p < 0.001) and thin-walled
      cavity (D >= 3 cm) (OR = 3.561, 95% CI: 1.394-9.097, p = 0.008) were also the
      independent predictors for the diagnosis of NTM-LD. CONCLUSIONS: Bronchiectasis
      in the right middle lobe or left lingual segment and thin-walled cavity with a
      diameter of more than 3 cm are the frequently the chest CT features in patients
      with NTM-LD, which might be helpful for an early diagnosis in patients with AFB
      smear positive.

PMID- 26214780
TI  - Catheter-related bloodstream infections by opportunistic pathogens in
      immunocompromised hosts.
AB  - Catheter-related bloodstream infections (CRBI) represent a frequent complication
      of immune-compromised hosts with a high mortality rate. In this setting,
      opportunistic pathogens can create a biofilm on implanted devices, being the
      source of infection. We provide a mini-review of the literature, starting from
      the description of two cases of CRBI by opportunistic pathogens in poly-morbid
      patients, successfully treated by antibiotic lock-therapy. 

PMID- 26214781
TI  - Mini invasive skeletal muscle biopsy technique with a tri-axial end cut needle.
AB  - OBJECTIVE: Skeletal Muscle Biopsy is a minor surgical procedure for the diagnosis
      of different neuromuscular pathological conditions and has recently gained
      popularity also in the research field of age-related muscular modifications and
      sarcopenia. Few studies focused on the application of mini-invasive muscular
      biopsy in both normal and pathological conditions. The aim of our study was to
      describe a mini invasive ultrasound-guided skeletal muscular biopsy technique in
      complete spinal cord injured (SCI) patients and healthy controls with a tri-axial
      end-cut needle. PATIENTS AND METHODS: Skeletal muscle biopsies were collected
      from 6 chronic SCI patients and 3 healthy controls vastus lateralis muscle with a
      tri-axial end cut needle (Biopince(c) - Angiotech). Muscle samples were stained
      for ATPase to determine fibers composition, moreover, gene expression of
      cyclooxygenase-1 (COX-1) and prostaglandin E2 receptor has been analyzed by Real
      Time RT-PCR. RESULTS: All the procedures were perfomed easily without failures
      and complications. Control tissue was macroscopically thicker than SCI one.
      Control specimen displayed an equal distribution of type I and type II fibers,
      while SCI sample displayed a prevalence of type II fibers SCI specimen displayed
      a significant reduction in COX-1 gene expression. This mini-invasive approach was
      easy, accurate and with low complication rate in performing skeletal muscle
      biopsy in both SCI patients and controls. CONCLUSIONS: This technique could be
      useful in conditions in which the overall quantity of specimen required is small
      like for molecular biology analysis. For histological diagnostic purposes and/or
      conditions in which the original tissue is already pathologically modified, this
      technique should be integrated with more invasive techniques.

PMID- 26214782
TI  - Neuropathophysiology of paroxysmal, systemic, and other related movement
      disorders.
AB  - Movement disorders are neurological conditions affecting the ability to produce
      and control voluntary as well as involuntary movements, and may be categorized
      into akinetic/rigid and hyperkinetic disorders. The hyperkinetic disorders are
      generally perceived as being the most difficult to diagnose correctly. They are
      manifested by excessive, abnormal involuntary movements, and are referred to as
      dyskinesias. The conditions are further designated paroxysmal dyskinesias when
      the abnormal movements occur episodically, followed by a rapid return to
      normality without impaired consciousness between episodes. The events can be
      precipitated by sudden voluntary movements, or may occur spontaneously at rest,
      or precipitated by exertion or sleep. Most conditions are either inherited or
      sporadic, and some cases are associated with specific conditions. Although
      clinical scenarios can be confusing, considerable advances in the phenotype
      characterisation and genetic studies have provided important information that
      allowed simplifying the clinical definitions and diagnosis of the paroxysmal
      dyskinesias. These advances have helped understand the pathophysiology of these
      disorders and their variants. 

PMID- 26214783
TI  - Epicardial adipose tissue thickness in patients with chronic obstructive
      pulmonary disease having right ventricular systolic dysfunction.
AB  - OBJECTIVE: The aim of the present study was to evaluate epicardial fat thickness
      (EFT) in patients with chronic obstructive pulmonary disease (COPD) having right
      ventricular systolic dysfunction (RVSD). PATIENTS AND METHODS: This study was
      comprised of 98 patients with COPD and 40 healthy controls. All the study
      participants underwent 2-dimensional, pulsed and tissue-doppler transthoracic
      echocardiographic examination for the measurements of EFT and parameters of right
      and left ventricular functions. Patients with COPD were divided into mild and
      severe RVSD groups according to right ventricular fractional area changes
      (RVFACs). RESULTS: Age, gender, prevalence of diabetes mellitus, hypertension,
      body-mass-index (BMI) and dyslipidemia were similar between COPD patients and
      controls, as were between mild, and severe RVSD groups. Prevalence of smoking
      were higher in COPD patients than in controls. Right ventricular end-diastolic
      diameter, myocardial performance index and peak pulmonary systolic pressure were
      found to be higher in COPD patients, while tricuspid annular plane systolic,
      excursion, isovolumic accelerating time, EFT and EFT/BMI were found to be lower
      in COPD patients. COPD patients with severe RVSD had thinner EFT and lower
      EFT/BMI values than those with mild RVSD (4.10 +/- 0.77 vs 5.48 +/- 1.28 mm, p <
      0.001, respectively). CONCLUSIONS: The present study shows that the EFT decreases
      in patients with COPD and it is also associated with the degree of RVSD.
      Therefore, evaluating EFT in patient with COPD may provide information about the
      severity of the disease.

PMID- 26214784
TI  - The combined effect of rosuvastatin and ischemic pre- or post-conditioning on
      myocardial ischemia-reperfusion injury in rat heart.
AB  - OBJECTIVE: To investigate the combined effect of rosuvastatin and ischemic
      preconditioning or postconditioning on ischemia-reperfusion injury in in vivo rat
      heart. MATERIALS AND METHODS: Ninenty-six male adult Wistar rats were randomly
      assigned to eight groups: Sham group, ischemia-reperfusion, rosuvastatin
      preconditioning, rosuvastatin postconditioning, ischemic preconditioning,
      ischemic postconditioning, ischemic + pharmacologic preconditioning and ischemic
      + pharmacologic postconditioning groups. Blood samples were taken for creatine
      kinase evaluation at selected time points. Six rats in each group were separated
      for either infarct size assessment or immunohistochemical staining with Bcl-2
      antibody. RESULTS: The staining with Bcl-2 was significantly lower in groups
      Sham, ischemic + pharmacologic preconditioning and ischemic + pharmacologic
      postconditioning groups which is well correlated with the decrease in infarct
      size for the same groups. The creatine kinase enzyme levels were also reduced to
      their lowest levels in ischemic + pharmacologic preconditioning and ischemic +
      pharmacologic postconditioning groups. CONCLUSIONS: These findings suggest that
      enriching the composition of reperfusate with rosuvastatin along with ischemic
      preconditioning or postconditioning procedures at the opposite sides of ischemia
      may interact synergistically for protecting ischemic myocardium from reperfusion
      injury. The combined application of rosuvastatin with ischemic preconditioning or
      ischemic postconditioning may provide a new therapeutic option in clinical
      interventions when compared to single treatment with ischemic and rosuvastatin
      preconditioning or postconditioning.

PMID- 26214785
TI  - Iginio Tansini revisited.
AB  - The origin of the muscolocutaneous latissimus dorsi flap dates back to 1906 when
      Igino Tansini, an Italian surgeon, described a procedure to reconstruct the
      mastectomy defect. After a detailed study of Tansini's original description and
      drawings, new insights about the pedicle of its compound flap have been found,
      showing that it has the same pedicle of the scapular flap. In the end, Tansini's
      flap should be more correctly considered as a compound musculocutaneous scapular
      flap. 

PMID- 26214786
TI  - Differential roles of Porphyromonas gingivalis lipopolysaccharide and Escherichia
      coli lipopolysaccharide in maturation and antigen-presenting functions of
      dentritic cells.
AB  - OBJECTIVE: The aim of this research is to study the roles of Porphyromonas
      gingivalis-lipopolysaccharide (P. gingivalis-LPS) and Escherichia coli
      lipopolysaccharide (E. coli-LPS) on maturation and antigen-presenting functions
      of dendritic cells (DCs), and to provide experimental evidences to explore the
      possible mechanism of DCs in periodontitis. MATERIALS AND METHODS: Flow cytometry
      was used to detect CD11c, MHC-II, CD80, CD86 and CD40 expression on DCs which
      were stimulated by P. gingivalis-LPS or E. coli-LPS and ELISA was used to detect
      IL-12, IFN-gamma, IL-10 and IL-13 secreted by DCs. CCK8 was used to assay CD4+T
      cells proliferation after co-cultured with DCs stimulated by P. gingivalis-LPS or
      E. coli-LPS and ELISA was used to detect IL-2, IFN-gamma, IL-10 and IL-13
      secreted by T cells. TLR4 inhibitor (polymyxin B) or TLR2 and TLR4 inhibitor
      (OxPAPC) was added to P. gingivalis-LPS group and E. coli-LPS group to observe
      the effects of these two TLR inhibitors on the maturation and antigen-presenting
      functions of DCs. RESULTS: The capacity of P. gingivalis-LPS to stimulate DCs
      maturation was similar to that of E. coli-LPS. The amount of IL-12 and IFN-gamma
      secreted by DCs in P. gingivalis-LPS group was significantly lower than that of
      E. coli-LPS group (p < 0.05), meanwhile, IL-10 and IL-13 secreted by DCs in P.
      gingivalis-LPS group was significantly higher than that of E. coli-LPS group (p <
      0.05). DCs stimulated by both P. gingivalis-LPS and E. coli-LPS could promote the
      proliferation of CD4+T cells. The amount of IL-2 and IFN-gamma secreted by T
      cells stimulated by DCs in P. gingivalis-LPS group was significantly lower than
      that of E. coli-LPS group (p < 0.05), meanwhile, IL-10 secreted by T cells
      stimulated by DCs in P. gingivalis-LPS group was significantly higher than that
      of E. coli-LPS group (p < 0.05). When TLR4 inhibitor was added to E. coli-LPS
      group, maturation and antigen-presenting functions of DCs were significantly
      inhibited. When TLR4 inhibitor was added to P. gingivalis-LPS group, maturation
      and antigen-presenting functions of DCs were not significantly inhibited. When
      TLR2 and TLR4 inhibitor was added to P. gingivalis-LPS group, maturation and
      antigen-presenting functions of DCs were significantly inhibited. CONCLUSIONS: P.
      gingivalis-LPS could prime DCs maturation and antigen-presenting functions. DCs
      stimulated by P. gingivalis-LPS are prone to induce a stronger Th2 cell responses
      while DCs stimulated by E. coli-LPS are prone to induce a stronger Th1 cell
      responses. P. gingivalis-LPS triggers DCs through TLR2 pathway while E. coli-LPS
      triggers DCs through TLR4 pathway.

PMID- 26214787
TI  - Anesthesia management for the super obese: is sevoflurane superior to propofol as
      a sole anesthetic agent? A double-blind randomized controlled trial.
AB  - OBJECTIVE: General anesthesia in obese patients is both challenging and
      demanding. With the rates of obesity in the general population increasing, more
      patients undergo bariatric surgery. The aim of this study was to compare the
      performance, effectiveness and recovery from anesthesia of sevoflurane and
      propofol in combination with remifentanil, with and without bispectral index
      (BIS) monitoring in super obese patients undergoing bariatric surgery. PATIENTS
      AND METHODS: In this prospective, double-blind, randomized, controlled study a
      total of 100 super obese patients (body mass index, BMI > 50 kg/m2) undergoing
      bariatric surgery were randomly allocated in four groups: a sevoflurane group (n
      = 25), a sevoflurane with BIS monitoring group (n = 25), a propofol group (n=25)
      and a propofol with BIS monitoring group (n=25). Hemodynamic parameters, depth of
      anesthesia, recovery from anesthesia and postoperative pain were recorded.
      RESULTS: The mean age of patients was 37.7 +/- 9.2 years and the median BMI was
      57.86 +/- 9.33. There were no statistically significant differences between the
      four groups with respect to patient characteristics, comorbidities and duration
      of surgery. The intraoperatively mean arterial pressure was significantly higher
      in both propofol groups. No significant difference was observed between the four
      groups in respect to heart rate changes during anesthesia. Although the time to
      eye-opening and extubation was significantly shorter in both propofol groups,
      recovery from anesthesia, assessed with the Aldrete, Chung and White recovery
      scores, was significantly faster in sevoflurane groups. No significant difference
      was observed in postoperative pain between the four groups. CONCLUSIONS: Although
      both propofol and sevoflurane provide adequate general anesthesia, sevoflurane
      may be preferable in super obese patients because of superior hemodynamic
      stability and faster recovery from anesthesia.

PMID- 26214788
TI  - Metformin plus proton pump inhibitors therapy: the cobalamin deficiency
      challenge.
AB  - OBJECTIVE: It is known in literature that metformin and proton pump inhibitors
      (PPIs) are associated to cobalamin levels reduction independently but still very
      little is known about the combination of the two drugs in cobalamin levels
      decrease. Currently there are no published data concerning the management of
      patients with cobalamin deficiency related to the concomitant use of the
      aforementioned drugs. CASE REPORT: We present the case of a 65 year-old white man
      with an history of renal cell carcinoma, melanoma and hepatic nodular sclerosis
      Hodgkin's lymphoma, who was under treatment with metformin because of diabetes
      and with pantoprazole because of Barrett's esophagus. He came to our attention
      because of a progressive reduction of cobalamin levels without related anemia. We
      decided to continue metformin and pantoprazole therapy and we treated the patient
      with intramuscular injection of cobalamin to avoid the vitamin deficiency
      consequences. DISCUSSION: Up to now no published data are available concerning
      the management of patients with cobalamin deficiency related to the concomitant
      use of metformin and PPIs. Our case report faces this clinical problem in terms
      of therapeutic management.

PMID- 26214789
TI  - A synergistic interaction between magnesium sulphate and ketamine on the
      inhibition of acute nociception in rats.
AB  - OBJECTIVE: Magnesium is an endogenous voltage-dependent NMDA receptor-channel
      blocker and ketamine is a non-competitive NMDA receptor antagonist. Magnesium may
      potentiate the effect of ketamine in analgesia and anaesthesia, but may also
      interact in an opposing manner. This study aimed at evaluating type of the
      interaction between magnesium sulphate and ketamine administered systemically in
      rats with an acute nociceptive pain (tail-immersion test). MATERIALS AND METHODS:
      Analgesic activity was assessed by tail-immersion test in male Wistar rats (200
      250 g). The distal 5 cm of the tail was immersed in a warm water bath (55 +/- 0.5
      degrees C) and the time for tail-withdrawal was measured as response latency.
      RESULTS: Magnesium sulphate (2.5-30 mg/kg, s.c.) and ketamine (2.5-30 mg/kg,
      i.p.) administered alone did not produce any effect. However, significant
      antinociception (synergistic interaction) was revealed at the following doses of
      ketamine: magnesium sulphate of 5:5 mg/kg, 2.5:5 mg/kg and 10:5 mg/kg. The effect
      was not dose-dependent, and a greater response was obtained when ketamine was
      administered before magnesium sulphate. CONCLUSIONS: This study revealed that (1)
      magnesium sulphate and ketamine given alone were not effective against acute
      nociceptive pain in rats, but (2) a combination of both drugs resulted in
      synergistically inhibited nociception, (3) which occurred only at selected low
      doses and proportions of the medications in a combination and (4) suggested the
      importance of the order of drug administration.

PMID- 26214790
TI  - Antidepressant activities of Feijoa sellowiana fruit.
AB  - OBJECTIVE: Many pharmacological activities have been reported for Feijoa
      sellowiana. The aim of present study was to investigate antidepressant activities
      of its leaf and fruit extracts. MATERIALS AND METHODS: Antidepressant activities
      of methanolic extracts were evaluated by modified forced swimming test (FST) and
      tail suspension tests (TST) in male Swiss albino mice. RESULTS: Extracts showed
      signicant antidepressant activity in both models. They shortened remarkably the
      immobility period in both FST and TST and exhibited a dose dependent activity (p
      < 0.001). Leaf extract showed better activity than fruit extract. At 800 mg kg-1,
      it showed far better activity than imipramine in FST (p < 0.001). Both extracts
      showed significantly better activity than imipramine in increasing climbing time
      (p < 0.001). They showed significant activity in increasing in swimming time as
      compared to the control group (p < 0.001). CONCLUSIONS: Our studies indicate that
      Feijoa showed significant antidepressant activity. It produced dose dependent
      effect on both models. It seems this effect is mainly mediated by inhibition of
      reuptake of catecholamines. These results introduced these plants as easily
      accessible source of natural antidepressant.

PMID- 26214791
TI  - Sex differences in the kinetic profiles of d- and l- methylphenidate in the
      brains of adult rats.
AB  - OBJECTIVE: Methylphenidate is commonly used in the treatment of Attention Deficit
      Hyperactivity Disorder and narcolepsy. Methylphenidate is administered as a
      racemic mixture of the d- and l- threo enantiomers; however, the d-enantiomer is
      primarily responsible for the pharmacologic activity. Previous studies of the
      behavioral effects of methylphenidate have highlighted sex differences in the
      responsiveness to the drug, namely an increased sensitivity of females to its
      stimulatory effects. These differences may be due to differences in the uptake,
      distribution, and elimination of methylphenidate from male and female brains.
      Therefore, we compared the pharmacokinetics of d- and l- threo methylphenidate in
      the brains of male and female rats. MATERIALS AND METHODS: Adult male and female
      Sprague-Dawley rats were injected with 5 mg/kg d, l- threo methylphenidate, and
      whole brains were collected at various time points following injection. We
      measured methylphenidate concentrations utilizing chiral high pressure liquid
      chromatography followed by mass spectrometry. RESULTS: Females exhibited
      consistently higher brain concentrations of both d- and l- methylphenidate and a
      slower clearance of methylphenidate from brain as compared to males, particularly
      with the active d-enantiomer. CONCLUSIONS: The increased sensitivity of females
      to methylphenidate may be partially explained by an increase in total brain
      exposure to the drug.

PMID- 26214792
TI  - Trade-offs between seed output and life span - a quantitative comparison of
      traits between annual and perennial congeneric species.
AB  - Perennial plants allocate more resources belowground, thus sustaining important
      ecosystem services. Hence, shifting from annual to perennial crops has been
      advocated towards a more sustainable agriculture. Nevertheless, wild perennial
      species have lower seed production than selected annuals, raising the questions
      of whether there is a fundamental trade-off between reproductive effort and life
      span, and whether such trade-off can be overcome through selection. In order to
      address these questions and to isolate life span from phylogenetic and
      environmental factors, we conducted a meta-analysis encompassing c. 3000
      congeneric annual/perennial pairs from 28 genera. This meta-analysis is
      complemented with a minimalist model of long-term productivity in perennial
      species. Perennials allocate more resources belowground and less to seeds than
      congeneric annuals, independently of selection history. However, existing
      perennial wheat and rice could achieve yields similar to annuals if they survived
      three years and each year doubled their biomass, as other perennial grasses do.
      Selected perennial crops maintain the large belowground allocation of wild
      perennials, and thus can provide desired regulatory ecosystem services. To match
      the seed yield of annuals, biomass production of perennial grains must be
      increased to amounts attained by some perennial grasses - if this goal can be
      met, perennial crops can provide a more sustainable alternative to annuals.

PMID- 26214793
TI  - "Mom, You Have to Trust Me".

PMID- 26214794
TI  - Erratum.

PMID- 26214795
TI  - Corrigendum.

PMID- 26214796
TI  - Spontaneously electrical solids in a new light.
AB  - Reflection-absorption infrared spectroscopy (RAIRS) of nitrous oxide (N2O) thin
      films is shown to provide an independent means of observing the spontelectric
      state, the first new structural phase of matter, with unique electrical
      properties, to have emerged in decades. The presence of a spontaneous and
      powerful static electric field within the film, the defining characteristic of
      spontelectric solids, is demonstrated through observations of longitudinal
      transverse optical (LO-TO) splitting in RAIR spectra, using an analysis based on
      the vibrational Stark effect. In particular the dependence of the LO-TO splitting
      on the film deposition temperature may be wholly attributed to the known
      temperature dependence of the spontelectric field. 

PMID- 26214797
TI  - High performance Li-ion sulfur batteries enabled by intercalation chemistry.
AB  - The unstable interface of lithium metal in high energy density Li sulfur (Li-S)
      batteries raises concerns of poor cycling, low efficiency and safety issues,
      which may be addressed by using intercalation types of anode. Herein, a new
      prototype of Li-ion sulfur battery with high performance has been demonstrated by
      coupling a graphite anode with a sulfur cathode (2 mA h cm(-2)) after
      successfully addressing the interface issue of graphite in an ether based
      electrolyte. 

PMID- 26214798
TI  - Role of mitochondrial dysfunction and dysregulation of Ca(2+) homeostasis in
      insulin insensitivity of mammalian cells.
AB  - Mitochondria and endoplasmic reticulum (ER) play an important role in the
      maintenance of intracellular Ca(2+) homeostasis, and their defects may be
      etiological factors contributing to insulin resistance and type 2 diabetes (T2D).
      Recent studies indicate that alterations of Ca(2+) levels and Ca(2+) -dependent
      signaling pathways can impede the insulin signaling cascade, resulting in insulin
      resistance of beta cells and insulin-responsive cells. Mitochondria-associated ER
      membranes (MAMs) are essential for efficient communication between the ER and
      mitochondria. Thus, abnormalities in the structure and function of MAMs in
      affected tissue cells in T2D are an important area of study. Recently, we
      demonstrated that a deficiency of Cisd2, an iron-sulfur protein localized on
      MAMs, could lead to mitochondrial dysfunction and disturbance of intracellular
      Ca(2+) homeostasis. Moreover, we first elucidated that defects in the function of
      MAMs in Ca(2+) uptake resulted in insulin insensitivity of adipocytes, which
      plays an important role in the pathogenesis of diabetes in Cisd2 knockout mice.
      On the basis of these observations, we suggest improving the bioenergetic
      function of mitochondria and the function of MAMs in maintaining Ca(2+)
      homeostasis as a novel strategy for the development of new therapeutics aimed at
      preventing and treating insulin resistance and T2D. 

PMID- 26214799
TI  - Selective electrochemical reduction of CO2 to CO on CuO-derived Cu nanowires.
AB  - In this work, we report a new synthesis method to prepare a Cu nanowire
      electrocatalyst for selective CO2 reduction at room temperature and atmospheric
      pressure. Cu nanowire array electrodes were prepared through a two-step synthesis
      of Cu(OH)2 and CuO nanowire arrays on Cu foil substrates and a subsequent
      electrochemical reduction of the CuO nanowire arrays. The Cu nanowire arrays are
      able to electrochemically reduce CO2 to CO with a faradaic efficiency of ~50% at
      a moderate overpotential of 490 mV, which is significantly higher than that of
      polycrystalline Cu foil catalysts at identical conditions. The improved faradaic
      efficiency for the reduction of CO2 to CO is ascribed to the enhanced
      stabilization for the CO2(-) intermediate on the high surface area Cu nanowire
      arrays. 

PMID- 26214800
TI  - Enhanced Performance of "Flower-like" Li4Ti5O12 Motifs as Anode Materials for
      High-Rate Lithium-Ion Batteries.
AB  - "Flower-like" motifs of Li4Ti5O12 were synthesized by using a facile and large
      scale hydrothermal process involving unique Ti foil precursors followed by a
      short, relatively low-temperature calcination in air. Moreover, a detailed time
      dependent growth mechanism and a reasonable reaction scheme were proposed to
      clearly illustrate and highlight the structural evolution and subsequent
      formation of this material. Specifically, the resulting "flower-like" Li4Ti5O12
      microspheres consisting of thin nanosheets provide for an enhanced surface area
      and a reduced lithium-ion diffusion distance. The high surface areas of the
      exposed roughened, thin petal-like component nanosheets are beneficial for the
      interaction of the electrolyte with Li4Ti5O12 , which thereby ultimately provides
      for improved high-rate performance and favorable charge/discharge dynamics.
      Electrochemical studies of the as-prepared nanostructured Li4Ti5O12 clearly
      revealed their promising potential as an enhanced anode material for lithium-ion
      batteries, as they present both excellent rate capabilities (delivering 148, 141,
      137, 123, and 60 mAh g(-1) under discharge rates of 0.2, 10, 20, 50, and 100 C,
      at cycles of 50, 55, 60, 65, and 70, respectively) and stable cycling performance
      (exhibiting a capacity retention of ~97 % from cycles 10-100, under a discharge
      rate of 0.2 C, and an impressive capacity retention of ~87 % by using a more
      rigorous discharge rate of 20 C from cycles 101-300).

PMID- 26214801
TI  - Automated Peritoneal Dialysis Is Associated with Better Survival Rates Compared
      to Continuous Ambulatory Peritoneal Dialysis: A Propensity Score Matching
      Analysis.
AB  - INTRODUCTION: The impact of peritoneal dialysis modality on patient survival and
      peritonitis rates is not fully understood, and no large-scale randomized clinical
      trial (RCT) is available. In the absence of a RCT, the use of an advanced
      matching procedure to reduce selection bias in large cohort studies may be the
      best approach. The aim of this study is to compare automated peritoneal dialysis
      (APD) and continuous ambulatory peritoneal dialysis (CAPD) according to
      peritonitis risk, technique failure and patient survival in a large nation-wide
      PD cohort. METHODS: This is a prospective cohort study that included all incident
      PD patients with at least 90 days of PD recruited in the BRAZPD study. All
      patients who were treated exclusively with either APD or CAPD were matched for 15
      different covariates using a propensity score calculated with the nearest
      neighbor method. Clinical outcomes analyzed were overall mortality, technique
      failure and time to first peritonitis. For all analysis we also adjusted the
      curves for the presence of competing risks with the Fine and Gray analysis.
      RESULTS: After the matching procedure, 2,890 patients were included in the
      analysis (1,445 in each group). Baseline characteristics were similar for all
      covariates including: age, diabetes, BMI, Center-experience, coronary artery
      disease, cancer, literacy, hypertension, race, previous HD, gender, pre-dialysis
      care, family income, peripheral artery disease and year of starting PD. Mortality
      rate was higher in CAPD patients (SHR1.44 CI95%1.21-1.71) compared to APD, but no
      difference was observed for technique failure (SHR0.83 CI95%0.69-1.02) nor for
      time till the first peritonitis episode (SHR0.96 CI95%0.93-1.11). CONCLUSION: In
      the first large PD cohort study with groups balanced for several covariates using
      propensity score matching, PD modality was not associated with differences in
      neither time to first peritonitis nor in technique failure. Nevertheless, patient
      survival was significantly better in APD patients.

PMID- 26214802
TI  - Improved Variable Selection Algorithm Using a LASSO-Type Penalty, with an
      Application to Assessing Hepatitis B Infection Relevant Factors in Community
      Residents.
AB  - OBJECTIVES: In epidemiological studies, it is important to identify independent
      associations between collective exposures and a health outcome. The current
      stepwise selection technique ignores stochastic errors and suffers from a lack of
      stability. The alternative LASSO-penalized regression model can be applied to
      detect significant predictors from a pool of candidate variables. However, this
      technique is prone to false positives and tends to create excessive biases. It
      remains challenging to develop robust variable selection methods and enhance
      predictability. MATERIAL AND METHODS: Two improved algorithms denoted the two
      stage hybrid and bootstrap ranking procedures, both using a LASSO-type penalty,
      were developed for epidemiological association analysis. The performance of the
      proposed procedures and other methods including conventional LASSO, Bolasso,
      stepwise and stability selection models were evaluated using intensive
      simulation. In addition, methods were compared by using an empirical analysis
      based on large-scale survey data of hepatitis B infection-relevant factors among
      Guangdong residents. RESULTS: The proposed procedures produced comparable or less
      biased selection results when compared to conventional variable selection models.
      In total, the two newly proposed procedures were stable with respect to various
      scenarios of simulation, demonstrating a higher power and a lower false positive
      rate during variable selection than the compared methods. In empirical analysis,
      the proposed procedures yielding a sparse set of hepatitis B infection-relevant
      factors gave the best predictive performance and showed that the procedures were
      able to select a more stringent set of factors. The individual history of
      hepatitis B vaccination, family and individual history of hepatitis B infection
      were associated with hepatitis B infection in the studied residents according to
      the proposed procedures. CONCLUSIONS: The newly proposed procedures improve the
      identification of significant variables and enable us to derive a new insight
      into epidemiological association analysis.

PMID- 26214803
TI  - Significant Correlation between Retinal Venous Tortuosity and Aqueous Vascular
      Endothelial Growth Factor Concentration in Eyes with Central Retinal Vein
      Occlusion.
AB  - PURPOSE: To determine whether the degree of venous tortuosity is significantly
      correlated with the aqueous vascular endothelial growth factor (VEGF)
      concentration in eyes with a central retinal vein occlusion (CRVO). METHODS: We
      reviewed the medical records of 32 eyes of 32 patients who had macular edema due
      to a CRVO. All of the patients were examined at the Nagoya University Hospital
      and were scheduled to receive an intravitreal injection of bevacizumab (IVB) or
      ranibizumab (IVR) within 12 weeks of the onset of the CRVO to treat the macular
      edema. Aqueous humor was collected just before the IVB or IVR, and the VEGF
      concentration was determined by enzyme-linked immunosorbent assay (ELISA). The
      venous tortuosity index was calculated by dividing the length of the retinal
      veins by the chord length of the same segment. The correlation between the mean
      tortuosity index of the inferotemporal and supratemporal branches of the retinal
      vein and the aqueous VEGF concentration was determined. RESULTS: The mean aqueous
      VEGF concentration was 384 +/- 312 pg/ml with a range of 90 to 1077 pg/ml. The
      degree of venous tortuosity was significantly correlated with the VEGF
      concentration in the aqueous. (r = 0.49, P = 0.004), with the foveal thickness (r
      = 0.40, P = 0.02), and with the best-corrected visual acuity (r = 0.38, P =
      0.03). CONCLUSIONS: The significant correlation between the aqueous VEGF
      concentration and the venous tortuosity indicates that the degree of retinal
      venous tortuosity can be used to identify eyes that are at a high risk of
      developing neovascularization.

PMID- 26214804
TI  - The Clinical Effectiveness and Cost-Effectiveness of Screening for Age-Related
      Macular Degeneration in Japan: A Markov Modeling Study.
AB  - OBJECTIVE: To investigate the cost-effectiveness of screening and subsequent
      intervention for age-related macular degeneration (AMD) in Japan. METHODS: The
      clinical effectiveness and cost-effectiveness of screening and subsequent
      intervention for AMD were assessed using a Markov model. The Markov model
      simulation began at the age of 40 years and concluded at the age of 90 years. The
      first-eye and second-eye combined model assumed an annual state-transition
      probability, development of prodromal symptoms, choroidal neovascularization
      (CNV), and reduction in visual acuity. Anti-vascular-endothelial-growth-factor
      (anti-VEGF) intravitreal injection therapy and photodynamic therapy (PDT) were
      performed to treat CNV. Intake of supplements was recommended to patients who had
      prodromal symptoms and unilateral AMD. Data on prevalence, morbidity, transition
      probability, utility value of each AMD patient, and treatment costs were obtained
      from published clinical reports. RESULTS: In the base-case analysis, screening
      for AMD every 5 years, beginning at the age of 50 years, showed a decrease of 41%
      in the total number of blind patients. The screening program reduced the
      incidence of blindness more than did the additional intake of supplements.
      However, the incremental cost-effectiveness ratio (ICER) of screening versus no
      screening was 27,486,352 Japanese yen (JPY), or 259,942 US dollars (USD) per
      quality-adjusted life year (QALY). In the sensitivity analysis, prodromal symptom
      related factors for AMD had great impacts on the cost-effectiveness of screening.
      The lowest ICER obtained from the best scenario was 4,913,717 JPY (46,470 USD)
      per QALY, which was approximately equal to the willingness to pay in Japan.
      CONCLUSIONS: Ophthalmologic screening for AMD in adults is highly effective in
      reducing the number of patients with blindness but not cost-effective as
      demonstrated by a Markov model based on clinical data from Japan.

PMID- 26214805
TI  - Adherence to Disease Modifying Drugs among Patients with Multiple Sclerosis in
      Germany: A Retrospective Cohort Study.
AB  - BACKGROUND: Long-term therapies such as disease modifying therapy for Multiple
      Sclerosis (MS) demand high levels of medication adherence in order to reach
      acceptable outcomes. The objective of this study was to describe adherence to
      four disease modifying drugs (DMDs) among statutorily insured patients within two
      years following treatment initiation. These drugs were interferon beta-1a i.m.
      (Avonex), interferon beta-1a s.c. (Rebif), interferon beta-1b s.c. (Betaferon)
      and glatiramer acetate s.c. (Copaxone). METHODS: This retrospective cohort study
      used pharmacy claims data from the data warehouse of the German Institute for
      Drug Use Evaluation (DAPI) from 2001 through 2009. New or renewed DMD
      prescriptions in the years 2002 to 2006 were identified and adherence was
      estimated during 730 days of follow-up by analyzing the medication possession
      ratio (MPR) as proxy for compliance and persistence defined as number of days
      from initiation of DMD therapy until discontinuation or interruption. FINDINGS: A
      total of 52,516 medication profiles or therapy cycles (11,891 Avonex, 14,060
      Betaferon, 12,353 Copaxone and 14,212 Rebif) from 50,057 patients were included
      into the analysis. Among the 4 cohorts, no clinically relevant differences were
      found in available covariates. The Medication Possession Ratio (MPR) measured
      overall compliance, which was 39.9% with a threshold MPR>=0.8. There were small
      differences in the proportion of therapy cycles during which a patient was
      compliant for the following medications: Avonex (42.8%), Betaferon (40.6%), Rebif
      (39.2%), and Copaxone (37%). Overall persistence was 32.3% at the end of the 24
      months observation period, i.e. during only one third of all included therapy
      cycles patients did not discontinue or interrupt DMD therapy. There were also
      small differences in the proportion of therapy cycles during which a patient was
      persistent as follows: Avonex (34.2%), Betaferon (33.4%), Rebif (31.7%) and
      Copaxone (29.8%). CONCLUSIONS: Two years after initiating MS-modifying therapy,
      only 30-40% of patients were adherent to DMDs.

PMID- 26214806
TI  - Coastal Upwelling Drives Intertidal Assemblage Structure and Trophic Ecology.
AB  - Similar environmental driving forces can produce similarity among geographically
      distant ecosystems. Coastal oceanic upwelling, for example, has been associated
      with elevated biomass and abundance patterns of certain functional groups, e.g.,
      corticated macroalgae. In the upwelling system of Northern Chile, we examined
      measures of intertidal macrobenthic composition, structure and trophic ecology
      across eighteen shores varying in their proximity to two coastal upwelling
      centres, in a hierarchical sampling design (spatial scales of >1 and >10 km). The
      influence of coastal upwelling on intertidal communities was confirmed by the
      stable isotope values (delta13C and delta15N) of consumers, including a dominant
      suspension feeder, grazers, and their putative resources of POM, epilithic
      biofilm, and macroalgae. We highlight the utility of muscle delta15N from the
      suspension feeding mussel, Perumytilus purpuratus, as a proxy for upwelling,
      supported by satellite data and previous studies. Where possible, we used
      corrections for broader-scale trends, spatial autocorrelation, ontogenetic
      dietary shifts and spatial baseline isotopic variation prior to analysis. Our
      results showed macroalgal assemblage composition, and benthic consumer assemblage
      structure, varied significantly with the intertidal influence of coastal
      upwelling, especially contrasting bays and coastal headlands. Coastal topography
      also separated differences in consumer resource use. This suggested that coastal
      upwelling, itself driven by coastline topography, influences intertidal
      communities by advecting nearshore phytoplankton populations offshore and cooling
      coastal water temperatures. We recommend the isotopic values of benthic
      organisms, specifically long-lived suspension feeders, as in situ alternatives to
      offshore measurements of upwelling influence. 

PMID- 26214807
TI  - Vaccination against IL-33 Inhibits Airway Hyperresponsiveness and Inflammation in
      a House Dust Mite Model of Asthma.
AB  - In several clinical and experimental studies IL-33 and its receptor have been
      found to play important roles in the development of asthma and allergic airway
      inflammation. We evaluated the effects of vaccination against IL-33 in a mouse
      model of airway inflammation induced by house dust mite (HDM) allergen. Balb/c
      mice received the IL-33 vaccine subcutaneously, followed by intranasal
      administration of HDM for up to six weeks. Vaccination against IL-33 induced high
      titers of specific anti-IL-33 IgG antibodies that inhibited HDM-induced airway
      hyperresponsiveness (AHR) in the conducting airways and tissue damping. The
      vaccination also attenuated the HDM-induced elevation in the numbers of
      eosinophils in bronchoalveolar lavage fluid (BALF) and suppressed the
      accumulation of inflammatory cells in the airways. Furthermore, the levels of IL
      17A, IL-25, IL-33 and TSLP in lung tissue homogenates were reduced by vaccination
      against IL-33. These observations demonstrate that vaccination against IL-33
      inhibits HDM-induced development of AHR, airway inflammation and production of
      inflammatory cytokines. The results also indicate an important role of IL-33 in
      the regulation of AHR of the distal lung compartments. Thus, administration of
      such a vaccine is potentially an effective therapeutic tool for treating allergic
      asthma. 

PMID- 26214810
TI  - Utilization and Safety of a Pulmonary Embolism Treatment Protocol in an Emergency
      Department Observation Unit.
AB  - Pulmonary embolism (PE) is a common disease in emergency medicine and treatment
      approaches vary greatly. Emergency department observation units (EDOUs) have
      provided the opportunity to complete a PE workup, initiate treatment, and arrange
      appropriate follow-up for low-risk patients. OBJECTIVE: We sought to evaluate the
      utilization and safety of a treatment protocol for low-risk PE in an EDOU.
      METHODS: A prospective evaluation was performed in our EDOU for the treatment of
      low-risk PE between December 1, 2010 and May 31, 2012. The PE treatment protocol
      included telemetry monitoring, initiation of anticoagulation, performance of an
      echocardiogram, bilateral lower extremity duplex ultrasound, and consultation by
      the hospital's thrombosis service to arrange outpatient follow-up. The primary
      outcome measure was inpatient admission and any complications during the EDOU
      stay or during a 30-day follow-up period. RESULTS: Twelve patients were assigned
      to the EDOU for the PE treatment protocol during the 18-month study period. Six
      patients (50%) were admitted to an inpatient unit following the EDOU stay.
      Reasons for inpatient admission included hypoxia/worsening dyspnea (2), right
      ventricular strain on echocardiogram (1), large clot burden on duplex ultrasound
      (1), and lack of availability of testing/thrombosis service consultation during
      the EDOU stay (2). There were no adverse events in the EDOU. All patients
      reported compliance with outpatient follow-up, and none of the patients reported
      hospitalization or adverse events during the 30-day follow-up period. Utilization
      of the PE treatment protocol in our EDOU was surprisingly low (<1 patient/month),
      possibly because of provider awareness of the protocol. CONCLUSIONS: Although the
      overall inpatient admission rate from the EDOU was high, some of these cases
      related to logistical issues rather than medical concerns or complications.
      Further evaluation of an EDOU PE protocol may continue to demonstrate the safety
      and efficiency of this approach when compared with inpatient admission.

PMID- 26214808
TI  - Assessment of Sex Differences for Treatment, Procedures, Complications, and
      Associated Conditions Among Adolescents Hospitalized with Crohn's Disease.
AB  - BACKGROUND: Sex differences among adults in healthcare treatment and outcomes
      have been reported; however, there is a paucity of literature regarding pediatric
      populations, particularly adolescents with Crohn's disease (CD). The objective
      was to identify whether sex differences exist with respect to complications,
      procedures, and medication usage (corticosteroids, biological agents, and total
      parenteral nutrition) among hospitalized adolescents with CD. METHODS:
      Adolescents with CD (n = 5782) hospitalized between April 1, 2004, and June 30,
      2012, were selected from the Pediatric Health Information System database with a
      1:1 ratio of males to females by hospital. Frequency of disease complications,
      associated conditions, procedures performed, and medication usage were analyzed
      with nonparametric statistical tests for the existence of sex differences.
      RESULTS: Five thousand seven hundred eighty-two patients were included with a
      median age of 15 years. Females were slightly more likely to have anemia (29%
      versus 25%, P = 0.012), infection (12% versus 8%, P = 0.001), and mood disorder
      (9% versus 6%, P < 0.001), whereas males had more maturational delays (3% versus
      1%, P = 0.004) and malnutrition (18% versus 14%, P = 0.027). Among procedures,
      only one category demonstrated a sex difference: females had more blood product
      transfusions (9% versus 6%, P < 0.001). Female rates for corticosteroids (62%),
      biological agents (16%), and total parenteral nutritionTPN (18%) were not
      statistically different from those for males (62%, 15%, and 20%, respectively).
      There were no differences in length of stay by sex. CONCLUSIONS: This cross
      sectional study of an administrative database identified few sex differences
      among adolescents with CD. The effect sizes were universally small and generally
      consistent with known sex differences unrelated to IBD.

PMID- 26214811
TI  - Acute Pulmonary Embolism Network and Multidisciplinary Response Team Approach to
      Treatment.
AB  - BACKGROUND: The ideal treatment strategy for acute pulmonary embolism (PE)
      remains a subject of debate. Treatment strategies vary based on numerous factors
      including the clinical scenario, hemodynamic variables, PE location, and
      personnel who are trained in advanced PE management therapies. METHODS: Similar
      to an acute myocardial infarction network, we created a regional referral system
      called the Acute PE Network to facilitate the transport of patients with PE from
      referring facilities and improve access to advanced therapies. Simultaneously, we
      created a multidisciplinary PE response team (PERT), developed diagnostic
      protocols, and created a therapeutic pathway that includes the use of ultrasound
      assisted catheter-directed thrombolysis (USAT) for submassive PE. Data were
      collected on patient characteristics, echocardiographic findings, and clinical
      outcomes for patients treated with USAT utilizing this pathway. RESULTS: From
      January 2012 to May 2014, 31 patients who were treated with USAT for acute PE
      were identified. Fourteen of these patients were transferred through our Acute PE
      Network, whereas 17 patients presented directly to the emergency department. All
      patients were consulted upon by our PERT. Among those patients who had both pre
      USAT and post-USAT echocardiograms performed for comparison (n = 19), right
      ventricular function improved or was preserved in 94% of patients, and right
      ventricular size improved or was preserved in 88% of patients. CONCLUSIONS:
      Through the development of an Acute PE Network, with incorporation of a PERT and
      implementation of a critical care pathway, we report an innovative treatment
      approach to acute PE that includes utilization of USAT for submassive PE.

PMID- 26214812
TI  - Prevalence and Overlap of Noncardiac Conditions in the Evaluation of Low-risk
      Acute Chest Pain Patients.
AB  - BACKGROUND: When patients present to the emergency department with a complaint
      concerning for heart disease, this often becomes the primary focus of their
      evaluation. While patients with noncardiac causes of chest pain outnumber those
      with cardiac causes, noncardiac etiologies are frequently overlooked. We
      investigated symptoms and noncardiac conditions in a cohort of patients with
      chest pain at low risk of cardiac disease. METHODS: We analyzed data from a
      prospective registry of patients who were evaluated in our chest pain evaluation
      center. Registry participants completed standardized and validated instruments
      for depression (by Patient Health Questionnaire PHQ-9), anxiety (by Generalized
      Anxiety Disorder GAD-7), and Gastroesophageal Reflux Disorder (GERD; by GERD
      Symptom Frequency Questionnaire). Chest pain characteristics were recorded;
      severity was reported on a 10-point scale. RESULTS: A total of 195 patients were
      included in the investigation. Using the instruments noted above, the prevalence
      of depression was 34%, anxiety was 30%, and GERD was 44%, each of at least
      moderate severity. 32.5% of patients had 2 or more conditions. The median for the
      severity of angina was 7/10 and the number of episodes over the preceding week
      was 2, respectively. Severity of angina was associated with PHQ-9 (r = 0.238; P <
      0.001) and GAD-7 (r = 0.283; P < 0.001) scores. The number of angina episodes
      over the prior week correlated with GERD Symptom Frequency Questionnaire (r =
      0.256; P < 0.001) and PHQ-9 (r = 0.175; P = 0.019) scores. No correlation was
      observed between any of the scores and body mass index, smoking tobacco, diabetes
      mellitus, hypertension, or hyperlipidemia. CONCLUSION: In our cohort of low-risk
      acute chest pain patients, depression, anxiety, and GERD were common, substantial
      overlap was observed. The severity of these noncardiac causes of chest pain
      causes correlated with the self-reported severity and frequency of angina, but
      weakly. These conditions should be part of a comprehensive plan of care for chest
      pain management.

PMID- 26214813
TI  - Temporal Trends in Disease Severity and Predicted Surgical Risk at the Time of
      Referral for Echocardiography in Patients Diagnosed with Aortic Stenosis.
AB  - BACKGROUND: Calcific aortic stenosis (AS) is the most common underlying pathology
      in patients undergoing heart valve surgery, with an expected increasing
      prevalence among the aging population. METHODS AND RESULTS: We identified the
      temporal trends in referral patterns, disease severity, and associated surgical
      risk among patients with AS between January 1, 1995 and December 31, 2012 at the
      Duke University Hospital. A total of 6103 patients had a finding of mild (n =
      3303), moderate (n = 1648), or severe AS (n = 1152) in a native aortic valve.
      Overall presence of severe AS increased significantly over time (P = 0.009) with
      the most substantial increase occurring from 2010 and onward. Median age upon
      referral (P < 0.001) and attendant predicted surgical risk (P < 0.001) increased
      significantly in the observation period among patients with a finding of severe
      AS. Among patients with a finding of severe AS, the proportion of patients aged
      older than 80 years increased to 51.0% in the most recent time period (2010-2012)
      compared with 32.6% in the preceding time period (P < 0.001 for overall time
      trend). Similarly, the proportion of patients with a logistic EuroSCORE greater
      than 20% increased to 21.3% (2010-2012) from 12.1% (pre-2010). CONCLUSIONS: Among
      patients referred for echocardiography to a high-volume tertiary hospital center,
      a significant increase in the prevalence of severe AS was observed over time.
      This trend occurred in parallel with increasing age and predicted surgical risk
      at referral. Health-care resource planning should account for an increasing
      number of patients in need of high-risk aortic valve replacements in the near
      future.

PMID- 26214815
TI  - Relationship Between Red Blood Cell Distribution Width and Mortality of Patients
      with Acute Myocardial Infarction Referring to Tehran Heart Center.
AB  - OBJECTIVE: Coronary heart disease is the most common cause of death in most
      countries and also in Iran. Among novel prognostic markers suggested in recent
      studies for coronary heart disease, red blood cell distribution width (RDW) has
      been found to be associated with poor prognosis. Therefore, we aimed to evaluate
      the relationship between RDW and 6-month mortality and cardiovascular events
      after the initial attack of myocardial infarction (MI). METHODS: Medical records
      of 642 patients with MI were investigated for basic and clinical characteristics,
      as well as patients' first hemoglobin, RDW, and mean corpuscular volume at the
      time of admission. Then based on patients' time of hospitalization, they were
      followed up by telephone for readmission and mortality 6 months later. RESULTS:
      Mean +/- SD age of patients was 62.7 +/- 12.7 years. In 6-month telephone follow
      up, 443 patients (69%) had readmission. Six-month mortality occurred in 70
      patients (10.9%). Patients with RDW level of 14.6% and higher were significantly
      older (P < 0.001). Three percent of patients with low RDW and 14.8% in high RDW
      group had renal failure (P < 0.001). Six-month mortality was observed in 24.3% of
      patients with high RDW and 7.9% of those with low RDW (P < 0.001). In
      multivariate logistic regression analysis, RDW (odds ratio: 1.98, 95% confidence
      interval: 1.06-3.68, P = 0.03), age, and ejection fraction were significant
      independent prognostic factors for mortality. CONCLUSIONS: Six-month mortality
      was significantly higher in patients with MI with high RDW. Thus given that RDW
      is an inexpensive and available laboratory test, it could be used for mortality
      risk assessment and follow up the patients for stricter control of other
      modifiable risk factors.

PMID- 26214816
TI  - Novel Hepatitis C Treatment and the Impact on Kidney Transplantation.
AB  - With a worldwide prevalence of 6% to 40% among patients with end-stage renal
      disease, hepatitis C virus (HCV) infection is a significant cause of comorbidity
      in kidney transplant candidates and recipients alike. Hepatitis C infection
      negatively impacts patient and allograft outcomes, predisposes to progressive
      liver disease and increases the risks of glomerular disease as well as new onset
      diabetes after transplantation. Treatment options until now have revolved around
      interferon, limited in efficacy, restricted to pretransplant administration
      because of concerns related to allograft dysfunction and immune stimulation, and
      fraught with high rates of intolerance. Direct-acting antivirals therapies are
      now emerging, providing the opportunity to effectively cure chronic HCV infection
      and to reduce the burden of hepatic and extrahepatic complications of HCV that
      are observed in kidney recipients, thereby offering hope of improved patient
      outcomes. Against a description of the major outcomes and risks that HCV+ kidney
      candidates and recipients encounter, and a summary of the pertinent studies of
      interferon-based therapies in this population, this review discusses the
      potential role for emerging direct-acting antivirals, proposing treatment
      algorithms that should be considered in the management of these complex patients.
      Conundrums relating to the new treatment, including the potential impact on the
      utilization of kidneys from HCV-infected donors, are presented. 

PMID- 26214818
TI  - Taming the Beast: Tailored Therapy for Hepatitis E in Organ Transplant
      Recipients.

PMID- 26214817
TI  - An Early Viral Response Predicts the Virological Response to Ribavirin in
      Hepatitis E Virus Organ Transplant Patients.
AB  - BACKGROUND: Ribavirin is efficient at treating chronic hepatitis E virus
      infection in solid-organ transplant patients. However, the early kinetics of
      viral replication under therapy and the impact of immunosuppressant regimens on
      viral replication are unknown: thus, determining the aim of our study. METHODS:
      Thirty-five patients with a solid-organ transplant and chronic hepatitis E virus
      infection were given ribavirin for 3 months. The hepatitis E virus (HEV) RNA
      concentrations were determined before treatment, at days 7, 15, and 21 and at
      months 1, 2, and 3 during therapy and after ribavirin cessation. RESULTS: A
      sustained virological response (SVR) occurred in 63%. Decreased viral
      concentration within the first week post-ribavirin therapy was an independent
      predictive factor for SVR, and a decreased HEV concentration of 0.5 log copies/mL
      or greater had an 88% positive predictive value. No correlation between ribavirin
      trough level on day 7 or at month 2 with a virological response or an SVR was
      observed. Before therapy, HEV RNA concentration was significantly greater in
      patients receiving mechanistic target of rapamycin inhibitor-based
      immunosuppression compared to patients given calcineurin inhibitors. The use of
      mycophenolic acid did not impact on the response to ribavirin. CONCLUSION: An
      early response to ribavirin can be used to define the optimal duration of therapy
      in the setting of HEV infection.

PMID- 26214819
TI  - Lanthanide Template Synthesis of Trefoil Knots of Single Handedness.
AB  - We report on the assembly of 2,6-pyridinedicarboxamide ligands (1) with point
      chirality about lanthanide metal ion (Ln(3+)) templates, in which the helical
      chirality of the resulting entwined 3:1 ligand:metal complexes is covalently
      captured by ring-closing olefin metathesis to form topologically chiral molecular
      trefoil knots of single handedness. The ligands do not self-sort (racemic ligands
      form a near-statistical mixture of homoleptic and heteroleptic lanthanide
      complexes), but the use of only (R,R)-1 leads solely to a trefoil knot of Lambda
      handedness, whereas (S,S)-1 forms the Delta-trefoil knot with complete
      stereoselectivity. The knots and their isomeric unknot macrocycles were
      characterized by NMR spectroscopy, mass spectrometry, and X-ray crystallography
      and the expression of the chirality that results from the topology of the knots
      studied by circular dichroism. 

PMID- 26214820
TI  - The State of Graduate Medical Education Funding and Meeting Our Nation's Health
      Care Needs.

PMID- 26214821
TI  - Accuracy of Anterior Superior Iliac Spine Symmetry Assessment by Routine
      Structural Examination.
AB  - CONTEXT: Assessment of the anterior superior iliac spine (ASIS) is a key
      component in generating the pelvic diagnosis of somatic dysfunction, but studies
      have shown poor reliability between examiners. OBJECTIVE: To assess the influence
      of homogeneous training, years of experience, and eye dominance on the percentage
      of correctness, sensitivity, and specificity of ASIS evaluation. METHODS:
      Osteopathic physicians, predoctoral teaching fellows, and first- and second-year
      osteopathic medical students from a single teaching institute assessed 3 plastic
      pelvic models with ASIS anatomic landmarks set at different levels: even and 5-
      and 10-mm descrepancies. Dominant and nondominant eyes were used independently to
      assess ASIS levels. RESULTS: A total of 147 examiners (participants) participated
      in this study (66 first-year and 61 second-year medical students, 15 fellows, and
      5 osteopathic physicians). The overall percentages of correct results were 31.0%
      (even levels), 82.8% (5-mm discrepancy), and 91.7% (10-mm discrepancy).
      Differences by level of training were statistically significant only for the 5-mm
      ASIS discrepancy, where participants with more experience performed better. The
      overall sensitivity was 82.8% (5-mm discrepancy) and 91.7% (10-mm discrepancy),
      and the specificity was 31.0%. No statistically significant differences were
      found in the percentage of correct results by eye dominance. CONCLUSION:
      Assessment of ASIS is sensitive but not specific at discrepancies of 5 mm or
      greater. Length of experience positively influences the percentage of correct
      results, and eye dominance does not significantly change this outcome. This form
      of assessment can be used to screen for ASIS asymmetry.

PMID- 26214822
TI  - Modeled Osteopathic Manipulative Treatments: A Review of Their in Vitro Effects
      on Fibroblast Tissue Preparations.
AB  - A key osteopathic tenet involves the body's ability to self-heal. Osteopathic
      manipulative treatment (OMT) has been evolved to improve this healing capacity.
      The authors' in vitro work has focused on modeling 2 common OMT modalities:
      myofascial release (MFR) and counterstrain. Their studies have evaluated the
      effects of these modalities on wound healing, cytokine secretion, and muscle
      repair. The key components of the host response to mechanical forces are
      fibroblasts, which are the main fascial cells that respond to different types of
      strain by secreting anti-inflammatory chemicals and growth factors, thus
      improving wound healing and muscle repair processes. The purpose of this review
      is to discuss the cellular and molecular mechanisms by which MFR and other OMT
      modalities work, in particular, the role of strained fibroblasts in inflammation,
      wound healing, and muscle repair and regeneration. Changing MFR parameters, such
      as magnitude, duration, direction, and frequency of strain, might uniquely affect
      the physiologic response of fibroblasts, muscle contraction, and wound healing.
      If such results are clinically translatable, the mechanisms underlying the
      clinical outcomes of OMT modalities will be better understood, and these
      treatments will be more widely accepted as evidence-based, first-line therapies. 

PMID- 26214823
TI  - Using Simulation-Based Medical Education to Meet the Competency Requirements for
      the Single Accreditation System.
AB  - Simulation-based medical education can provide medical training in a
      nonjudgmental, patient-safe, and effective environment. Although simulation has
      been a relatively new addition to medical education, the aeronautical, judicial,
      and military fields have used simulation training for hundreds of years, with
      positive outcomes. Simulation-based medical education can be used in a variety of
      settings, such as hospitals, outpatient clinics, medical schools, and simulation
      training centers. As the author describes in the present article, residencies
      currently accredited by the American Osteopathic Association can use a simulation
      based medical education curriculum to meet training requirements of the 6
      competencies identified by the Accreditation Council for Graduate Medical
      Education. The author also provides specific guidance on providing training and
      assessment in the professionalism competency. 

PMID- 26214824
TI  - Role Modeling in the First 2 Years of Medical School.
AB  - Role modeling opportunities for osteopathic physician teachers during a student's
      first 2 years of medical school are emerging as more colleges of osteopathic
      medicine strive to connect basic science didactics with clinically based learning
      activities. Examples of positive modeling by physician teachers during the first
      years of medical school are illustrated by 10 vignettes that can be incorporated
      into faculty development programs to increase awareness of such opportunities.
      The physician teacher in each vignette interacts with the student demonstrating
      desired professional behaviors. These vignettes also illustrate the effect of a
      positive "hidden curriculum" on a student's professional development. By
      recognizing these valuable teachable moments, teachers can incorporate role
      modeling into their daily practice. 

PMID- 26214825
TI  - Bilateral Shoulder Dislocation Presenting as a Unilateral Shoulder Dislocation:
      Case Report.
AB  - Shoulder dislocations are a common condition seen by orthopedic surgeons and
      emergency medicine physicians. Shoulder dislocations typically present
      unilaterally and are anterior in nature. Bilateral simultaneous posterior
      shoulder dislocations are typically associated with seizure or electrocution and
      are more common than bilateral simultaneous anterior dislocations, which occur
      because of trauma or fall. In a traumatic setting, a shoulder dislocation may be
      accompanied by a distracting injury, and a thorough examination must be conducted
      to avoid overlooking concomitant diagnosis. The authors highlight the case of a
      patient who presented to the emergency department with the rare incidence of
      traumatic bilateral anterior shoulder dislocations, which resolved after 2 closed
      reductions. Orthopedic surgery and emergency medicine teams must maintain a high
      index of suspicion for injury to the contralateral limb to avoid missing
      pathologic changes due to distracting injuries. 

PMID- 26214826
TI  - Iliac Crest Herniation Secondary to Autogenous Bone Grafting Found on Osteopathic
      Examination.
AB  - Surgical repair of difficult or nonunion fractures is frequently performed with
      autogenous bone grafts, most commonly from the iliac crest. Complications from
      this procedure may include vessel injury, nerve injury, pelvic instability, bowel
      herniation, and ileus. The authors report a case of iliac crest herniation in a
      patient presenting with a small-bowel obstruction 2 years after anterior iliac
      crest graft harvest for an open reduction and internal fixation repair of a right
      humeral shaft fracture. An emergency operation revealed that the right colon had
      herniated through an opening in the right iliac crest. The appendix had adhered
      to new osseous bone formed postoperatively, requiring an appendectomy. The hernia
      defect was successfully repaired with polypropylene mesh. A high index of
      suspicion for graft site herniation is needed for patients with a history of
      iliac crest bone grafting who present with symptoms of abdominal pain, flank or
      hip pain, ileus, or small-bowel obstruction. 

PMID- 26214827
TI  - Little League Shoulder.

PMID- 26214828
TI  - A Physician's Living Will-'Till Death Do Us Part.

PMID- 26214831
TI  - XMCD studies of thin Co films on BaTiO3.
AB  - Different layer thicknesses of cobalt ranging from 2.6 A (1.5 ML) up to 55 A
      (30.5 ML) deposited on ferroelectric BaTiO3 have been studied regarding their
      magnetic behavior. The layers have been characterized using XMCD spectroscopy at
      remanent magnetization. After careful data analysis the magnetic moments of the
      cobalt could be determined using the sum rule formalism. There is a sudden and
      abrupt onset in magnetism starting at thicknesses of 9 A (5 ML) of cobalt for
      measurements at 120 K and of 10 A (5.5 ML) if measured at room temperature.
      Initial island growth and subsequent coalescence of Co on BaTiO3 is suggested to
      explain the sudden onset. In that context, no magnetically dead layers are
      observed. 

PMID- 26214829
TI  - Prevalence of Non-Volitional Sex Types and Associated Factors: A National Sample
      of Young People.
AB  - BACKGROUND: Non-volitional sex (NVS) in young people continues to be a major
      public health problem with long-term negative health outcomes. For the first
      time, the prevalence of different types of NVS and associated factors are
      compared between young people with same-sex sexual activities and those who have
      not. METHODS: We obtained data from 10,401 young women and men (aged 12 to 25
      years) who participated in a population study on sexual health, the Netherlands.
      We calculated and compared the prevalence of six types of NVS between women who
      had sex with men (yWSM) or women (yWSW), and men who had sex with women (yMSW) or
      men (yMSM). In sexually experienced participants (n = 5986) logistic regression
      analyses were applied to assess associations with NVS by assault or penetration.
      Analyses were weighted to represent the Dutch population. RESULTS: The prevalence
      of NVS ranged from 1% to 61%, depending on type. Prevalence was higher for young
      women (any: 40.6%) than men (any: 20.4%), and highest for yMSM and yWSW.
      Prevalence of NVS by assault or penetration was related to a range of socio
      demographic, behavioral and social factors, which were largely similar regardless
      of sex or same-sex-experiences. The NVS perpetrators were in over 70% of cases
      known to the victim; 1 in 4 cases of NVS by penetration were accompanied by
      violence. CONCLUSION: A substantial proportion of young people in the Netherlands
      have experienced NVS. Medical professionals, educators and caregivers should
      integrate services to continue to address NVS by targeting young people's
      multifaceted risk profiles and evidenced based interventions for doing so are
      needed.

PMID- 26214830
TI  - Rotavirus Gastroenteritis in a Neonatal Unit of a Greek Tertiary Hospital:
      Clinical Characteristics and Genotypes.
AB  - INTRODUCTION: Rotavirus (RV) infection in neonatal age can be mild or even
      asymptomatic. Several studies have reported that RV is responsible for 31%-87% of
      pediatric nosocomial diarrhea and causes gastroenteritis outbreaks in pediatric
      and neonatal units. OBJECTIVES: Study clinical characteristics, genotypes and
      risk factors of RV infection in neonatal age. METHODS: A prospective study was
      conducted from April 2009 till April 2013 in the neonatal special care unit of
      the largest tertiary pediatric hospital of Greece. Fecal samples and
      epidemiological data were collected from each neonate with gastrointestinal
      symptoms. RV antigen was detected with a rapid immunochromatography test. RV
      positive samples were further genotyped with RT PCR and sequencing using specific
      VP7 and VP4 primers. RESULTS: Positive for RV were 126/415 samples (30.4%). Mean
      age of onset was 18 days. Seventy four cases (58%) were hospital acquired.
      Seasonality of RV infection did not differ significantly throughout the year with
      the exception of 4 outbreaks. Genotypes found during the study period were G4P[8]
      (58.7%), G1P[8] (14.7%), G12P[8] (9.3%), G3P[8] (9.3%), G12P[6] (5.3%), G9P[8]
      (1.3%) and G2P[4] (1.3%). RV cases presented with: diarrhea (81%), vomiting
      (26.2%), fever (34.9%), dehydration (28.6%), feeding intolerance (39.7%), weight
      loss (54%), whilst 19% of cases were asymptomatic. Comparing community with
      hospital acquired cases differences in clinical manifestations were found.
      CONCLUSIONS: Significant incidence of nosocomially transmitted RV infection in
      neonatal age including asymptomatic illness exists. Genotypes causing nosocomial
      outbreaks are not different from community strains. Circulating vaccines can be
      effective in prevention of nosocomial RV infection through herd immunity.

PMID- 26214832
TI  - OUTPATIENT MEDICATION USE AND IMPLICATIONS FOR DENTAL CARE: GUIDANCE FOR
      CONTEMPORARY DENTAL PRACTICE.
AB  - BACKGROUND: Adverse effects of medication used in dental care are likely to
      increase as North Americans live longer, experience more and greater severity of
      chronic conditions and take more medications. Thus, documentation of medication
      use and the implications for contemporary dental practice is of increasing
      importance. METHODS: We recorded medication use in patients referred to a large
      private periodontal practice in Ottawa, Ontario. Patients self-reported
      medication use and medication allergies in their health history forms on
      admission. RESULTS: Of 322 sequential patients enrolled, 164 were female and the
      overall median age was 52 (range 6-94 years). Participants reported taking 249
      unique medications in 28 categories. Two-thirds of patients (63.7%) were taking
      prescription or over-the-counter (OTC) medications or both. The average number of
      medications per patient was 1.9 (range 0-14). The average number of OTC
      medications per patient was 0.5 for those not taking prescription medications and
      0.4 for patients taking prescription medications concurrently. The number of OTC
      products per patient was 0-7. CONCLUSIONS: Given the prevalence of the use of
      both prescription and OTC products, accurate recording of the medication profile
      is necessary in contemporary dental practice. Medication use and medication
      allergies provide information on patients' medical history and diagnoses that may
      have implications for their oral condition and delivery of dental care.
      Additional concerns include potential interactions between frequently used
      medications reported by patients and medications that are commonly used in
      dentistry. CLINICAL IMPLICATIONS: The increase in the use of multiple medications
      and OTC products by the outpatient community has an impact on dental care and
      prescribed medications in dental care. Thus, it is important to have a complete
      and accurate medication history to ensure a high standard of care in dental
      practice.

PMID- 26214833
TI  - RADIATION-INDUCED MUCOSITIS IN PATIENTS WITH HEAD AND NECK CANCER: SHOULD THE
      SIGNS OR THE SYMPTOMS BE MEASURED?
AB  - OBJECTIVE: To improve understanding of how patient-reported outcomes following
      radiation therapy for head and neck cancer may be influenced by factors beyond
      the local effects of the radiotherapy. METHODS: Initially, 50 patients with head
      and neck cancer who were scheduled to undergo radiation therapy consented to
      participate in this prospective observational study. The participants underwent
      an oral examination before commencement of therapy and twice weekly over the
      therapy period. The 33 participants who finished the therapy underwent one more
      examination 4 to 6 weeks after its completion. At each session, clinical signs of
      oral mucositis were recorded with clinician-based scoring tools, and participants
      completed a questionnaire based on a visual analogue scale to record the
      perceived degree of impairment of common oral functions caused by oral mucositis.
      The strength of the correlation between these signs and symptoms at various
      points throughout the study period was appraised using a linear mixed model with
      robust repeated measures. The study participants with the most extensive
      manifestations of oral mucositis but only minor pain and limited adverse effects
      on oral functions (n=6) were contrasted with those who had limited mucositis but
      more severe pain and adverse effects (n=7). In addition, study participants with
      poor to moderate correlations between signs and symptoms (n=5) were contrasted
      with those who had very good correlations (n=10). Simple bivariate tests were
      used for these comparisons. RESULTS: Correlations between various signs and
      symptoms at all time points varied markedly at the individual level. The
      characteristics of study participants in the 2 subcohorts defined by poor to
      moderate and very good correlations between signs and symptoms were comparable,
      except perhaps in terms of age (p<0.05, t test). Similarly, the participants in
      the 2 subcohorts defined by high manifestation with minor complaints and vice
      versa did not differ with regard to the variables recorded. CONCLUSION: Patients
      with head and neck cancer often report adverse effects of radiation-related oral
      mucositis on daily oral functions that are discordant with objective clinical
      findings. Patient-reported outcomes should be included in any interventional
      studies of oral mucositis, and trends over time should be analyzed within
      individuals, rather than between individuals.

PMID- 26214834
TI  - ANATOMICAL VARIATIONS OF THE GREATER PALATINE NERVE IN THE GREATER PALATINE
      CANAL.
AB  - The greater palatine nerve and the greater palatine canal are common sites for
      maxillary anesthesia during dental and maxillo-facial procedures. The greater
      palatine nerve is thought to course as a single trunk through the greater
      palatine canal, branching after its exit from the greater palatine foramen. We
      describe intra-canalicular branching variations of the greater palatine nerve
      found in 8 of 20 embalmed dissection specimens. Such variation is previously
      unreported in the literature. We characterize the variations in branching pattern
      and discuss the possible implications for clinical practice. 

PMID- 26214835
TI  - Femoral head bone viability after free vascularized fibular grafting for
      osteonecrosis: SPECT/CT study.
AB  - PURPOSE: To evaluate femoral head bone viability following free vascularized
      fibular grafting (FVFG) for osteonecrosis using SPECT/CT imaging. METHODS: Ten
      hips (9 patients) with osteonecrosis of the femoral head (ONFH) undergoing FVFG
      were prospectively enrolled. Four cases showed ARCO stage II, while six showed
      ARCO stage III. The mean age at surgery was 15.7 years (range, 13-22 years). Hip
      Harris Score (HHS) was measured pre- and post-operative. Bone scintigraphy with
      SPECT/CT was performed at 2 weeks and 6 months following surgery. RESULTS: Mean
      follow-up was 4.0 years (range, 2-5.9 years). Mean HHS increased from 37.2 to
      92.3. SPECT/CT findings revealed a progressive increase of femoral head uptake in
      all cases, suggesting subchondral graft bone viability. No progressive
      deformation of the femoral head was evidenced in radiographic evaluation at final
      follow-up. CONCLUSIONS: This study demonstrates FVFG's capacity for revitalizing
      femoral head subchondral bone grafting in patients with ONFH, surgically treated
      following Urbaniak's technique. (c) 2015 Wiley Periodicals, Inc. Microsurgery
      36:573-577, 2016.

PMID- 26214837
TI  - Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via
      LFA-1 integrin.
AB  - Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune
      cells have been shown to contribute to disease pathogenesis. In two transgenic
      models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated
      and were present in areas with amyloid-beta (Abeta) deposits, where they released
      neutrophil extracellular traps (NETs) and IL-17. Abeta42 peptide triggered the
      LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin
      ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS
      and intraparenchymal motility. In transgenic Alzheimer's disease models,
      neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade
      reduced Alzheimer's disease-like neuropathology and improved memory in mice
      already showing cognitive dysfunction. Temporary depletion of neutrophils for 1
      month at early stages of disease led to sustained improvements in memory.
      Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from
      cognitive decline and had reduced gliosis. In humans with Alzheimer's disease,
      neutrophils adhered to and spread inside brain venules and were present in the
      parenchyma, along with NETs. Our results demonstrate that neutrophils contribute
      to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the
      inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease. 

PMID- 26214836
TI  - The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly
      normalized after treatment.
AB  - We carried out metagenomic shotgun sequencing and a metagenome-wide association
      study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals
      with rheumatoid arthritis (RA) and healthy controls. Concordance was observed
      between the gut and oral microbiomes, suggesting overlap in the abundance and
      function of species at different body sites. Dysbiosis was detected in the gut
      and oral microbiomes of RA patients, but it was partially resolved after RA
      treatment. Alterations in the gut, dental or saliva microbiome distinguished
      individuals with RA from healthy controls, were correlated with clinical measures
      and could be used to stratify individuals on the basis of their response to
      therapy. In particular, Haemophilus spp. were depleted in individuals with RA at
      all three sites and negatively correlated with levels of serum autoantibodies,
      whereas Lactobacillus salivarius was over-represented in individuals with RA at
      all three sites and was present in increased amounts in cases of very active RA.
      Functionally, the redox environment, transport and metabolism of iron, sulfur,
      zinc and arginine were altered in the microbiota of individuals with RA.
      Molecular mimicry of human antigens related to RA was also detectable. Our
      results establish specific alterations in the gut and oral microbiomes in
      individuals with RA and suggest potential ways of using microbiome composition
      for prognosis and diagnosis. 

PMID- 26214838
TI  - Effects of Fatigue on Running Mechanics: Spring-Mass Behavior in Recreational
      Runners After 60 Seconds of Countermovement Jumps.
AB  - The purpose of this study was to investigate the effects of acute fatigue on
      spring-mass model (SMM) parameters among recreational runners at different
      speeds. Eleven participants (5 males and 6 females) performed running trials at
      slower, self-selected, and faster speeds on an indoor track before and after
      performing a fatigue protocol (60 s of countermovement jumps). Maximal vertical
      force (Fmax), impact peak force (Fpeak), loading rate (LR), contact time (Tc),
      aerial time (Ta), step frequency (SF), step length (SL), maximal vertical
      displacement of the center of mass (DeltaZ), vertical stiffness (Kvert), and leg
      work (Wleg) were measured using a force plate integrated into the track. A
      significant reduction (-43.1 +/- 8.6%; P < .05) in mechanical power during jumps
      indicated that the subjects became fatigued. The results showed that under
      fatigue conditions, the runners adjusted their running mechanics at slower (~2.7
      ms-1; DeltaZ -12% and SF +3.9%; P < .05), self-selected (~3.3 ms-1; SF +3%, SL 
      6.8%, Ta -16%, and Fmax -3.3%; P < .05), and faster (~3.6 ms-1 SL -6.9%, Ta -14%
      and Fpeak -9.8%; P < .05) speeds without significantly altering Kvert (P > .05).
      During constant running, the previous 60 s of maximal vertical jumps induced
      mechanical adjustments in the spatiotemporal parameters without altering Kvert. 

PMID- 26214839
TI  - Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens.
AB  - Could some vaccines drive the evolution of more virulent pathogens? Conventional
      wisdom is that natural selection will remove highly lethal pathogens if host
      death greatly reduces transmission. Vaccines that keep hosts alive but still
      allow transmission could thus allow very virulent strains to circulate in a
      population. Here we show experimentally that immunization of chickens against
      Marek's disease virus enhances the fitness of more virulent strains, making it
      possible for hyperpathogenic strains to transmit. Immunity elicited by direct
      vaccination or by maternal vaccination prolongs host survival but does not
      prevent infection, viral replication or transmission, thus extending the
      infectious periods of strains otherwise too lethal to persist. Our data show that
      anti-disease vaccines that do not prevent transmission can create conditions that
      promote the emergence of pathogen strains that cause more severe disease in
      unvaccinated hosts.

PMID- 26214840
TI  - Biological control of toxigenic citrus and papaya-rotting fungi by Streptomyces
      violascens MT7 and its extracellular metabolites.
AB  - An Indian indigenous, Loktak Lake soil isolate Streptomyces violascens MT7 was
      assessed for its biocontrol potential both in vitro and in vivo against toxigenic
      fruit-rotting fungi. Strain MT7 exhibited broad-spectrum antifungal activity
      against various pathogenic postharvest fungi of citrus and papaya. In shake-flask
      fermentation, antagonist S. violascens MT7 highly produced extracellular
      antifungal metabolites in early stationary growth phase in glucose-yeast extract
      malt extract (M93) broth. Both extracellular culture fluid (ECF) and its n
      butanol extract showed significant broad-spectrum fungal mycelial inhibition of
      several tested fruit-rotting fungi. Antifungal metabolite was found to be heat
      stable, nonpeptidic, and polyene type antibiotic. The lowest minimum inhibitory
      concentration (MIC) of n-butanol extract against Colletotrichum gloeosporioides
      MTCC 9664 and Aspergillus niger MTCC 281 was 0.0312 and 0.0625 mg/ml,
      respectively. Purification of n-butanol extract through silica gel chromatography
      resulted in partial purification of bioactive metabolite and the TLC
      autobiography revealed the presence of single antifungal metabolite with Rf value
      of 0.755. In vivo bioassays demonstrated the biocontrol potential of tested
      biocontrol agents on fruit-rotting fungi. Use of cell suspension of S. violascens
      MT7, extracellular metabolite(s), and n-butanol extract significantly (p < 0.05)
      reduced sour-rot development on Citrus reticulata Blanco (oranges) and soft-rot
      development on papaya fruits. Therefore, these results strongly suggest a high
      potential for application of S. violascens MT7 and its extracellular metabolites
      as an effective eco-friendly alternative to synthetic fungicides for controlling
      toxigenic citrus and papaya-rotting fungi.

PMID- 26214842
TI  - Medicine in a Disaster Area: Lessons From the 2015 Earthquake in Nepal.

PMID- 26214841
TI  - A powerful test for Balaam's design.
AB  - The crossover trial design (AB/BA design) is often used to compare the effects of
      two treatments in medical science because it performs within-subject comparisons,
      which increase the precision of a treatment effect (i.e., a between-treatment
      difference). However, the AB/BA design cannot be applied in the presence of
      carryover effects and/or treatments-by-period interaction. In such cases,
      Balaam's design is a more suitable choice. Unlike the AB/BA design, Balaam's
      design inflates the variance of an estimate of the treatment effect, thereby
      reducing the statistical power of tests. This is a serious drawback of the
      design. Although the variance of parameter estimators in Balaam's design has been
      extensively studied, the estimators of the treatment effect to improve the
      inference have received little attention. If the estimate of the treatment effect
      is obtained by solving the mixed model equations, the AA and BB sequences are
      excluded from the estimation process. In this study, we develop a new estimator
      of the treatment effect and a new test statistic using the estimator. The aim is
      to improve the statistical inference in Balaam's design. Simulation studies
      indicate that the type I error of the proposed test is well controlled, and that
      the test is more powerful and has more suitable characteristics than other
      existing tests when interactions are substantial. The proposed test is also
      applied to analyze a real dataset.

PMID- 26214843
TI  - Interpreting the real-time dynamic 'sliding sign' and predicting pouch of Douglas
      obliteration: an interobserver, intraobserver, diagnostic-accuracy and learning
      curve study.
AB  - OBJECTIVE: To determine inter- and intraobserver agreement, diagnostic accuracy
      and the learning curve required for interpreting the 'sliding sign' and
      predicting pouch of Douglas (POD) obliteration. METHODS: This was an inter
      /intraobserver, diagnostic-accuracy and learning-curve study involving six
      observers with different medical backgrounds, clinical skill sets and prior
      gynecological ultrasound experience: five non-specialist observers who had
      performed 0-750 previous gynecological scans and an expert sonologist who had
      performed  > 15 000. Following a formal theoretical and practical training
      session, they each viewed 64 offline transvaginal ultrasound (TVS) 'sliding-sign'
      videos from two anatomical locations (retrocervix and posterior uterine fundus
      (PUF)) in 32 women presenting with chronic pelvic pain, interpreting the videos
      as positive or negative for sliding sign and predicting, on that basis, the POD
      status. For intraobserver agreement analysis they re-analyzed the same video
      sets, in a different order, at least 7 days later. The expert sonologist was the
      reference standard for interpreting the sliding sign and the gold standard,
      laparoscopy, was used for the POD analysis. Learning-curve cumulative summation
      (LC-CUSUM) tests were conducted to assess if observer performance reached
      acceptable levels, using LC-CUSUM score < -2.45 as a cut-off. RESULTS: With
      respect to interpretation of the sliding sign, the overall multiple-rater
      agreement was moderate (Fleiss' kappa, K = 0.499). Observers were more consistent
      in their interpretation of the second compared with the first observation set (K
      = 0.547 vs 0.453) and for the retrocervical compared with the PUF region (K =
      0.556 vs 0.346). Regarding prediction of POD status, the accuracy, sensitivity,
      specificity and positive and negative predictive values for individual observers
      ranged from 65.4 to 96.2%, 80.0 to 100%, 64.7 to 100%, 50.0 to 100% and 94.7 to
      100%, respectively. Using LC-CUSUM score < -2.45, the observer with experience of
      200 previous gynecological scans reached acceptable levels for predicting POD
      obliteration and interpreting the sliding sign at each region (retrocervix and
      PUF) at 39, 54 and 28 videos and the observer with experience of 750 scans at 56,
      53 and 53 videos. CONCLUSIONS: Performance of a minimum number of gynecological
      ultrasound examinations is necessary for interpreting offline videos of the real
      time dynamic sliding sign and predicting POD obliteration. Non-specialist
      observers with prior experience of 200 or more gynecological scans were more
      consistent in interpreting the sliding sign at the retrocervix vs PUF. Copyright
      (c) 2015 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 26214844
TI  - Doctors or mid-level providers for abortion.
AB  - BACKGROUND: The World Health Organization recommends that abortion can be
      provided at the lowest level of the healthcare system. Training mid-level
      providers, such as midwives, nurses and other non-physician providers, to conduct
      first trimester aspiration abortions and manage medical abortions has been
      proposed as a way to increase women's access to safe abortion procedures.
      OBJECTIVES: To assess the safety and effectiveness of abortion procedures
      administered by mid-level providers compared to doctors. SEARCH METHODS: We
      searched the CENTRAL Issue 7, MEDLINE and POPLINE databases for comparative
      studies of doctor and mid-level providers of abortion services. We searched for
      studies published in any language from January 1980 until 15 August 2014.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) (clustered or not
      clustered), prospective cohort studies or observational studies that compared the
      safety or effectiveness (or both) of any type of first trimester abortion
      procedure, administered by any type of mid-level provider or doctors, were
      eligible for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two
      independent review authors screened abstracts for eligibility and double
      extracted data from the included studies using a pre-tested form. We meta
      analysed primary outcome data using both fixed-effect and random-effects models
      to obtain pooled risk ratios (RR) with 95% confidence intervals (CIs). We carried
      out separate analyses by study design (RCT or cohort) and type of abortion
      procedure (medical versus surgical). MAIN RESULTS: Eight studies involving 22,018
      participants met our eligibility criteria. Five studies (n = 18,962) assessed the
      safety and effectiveness of surgical abortion procedures administered by mid
      level providers compared to doctors. Three studies (n = 3056) assessed the safety
      and effectiveness of medical abortion procedures. The surgical abortion studies
      (one RCT and four cohort studies) were carried out in the United States, India,
      South Africa and Vietnam. The medical abortion studies (two RCTs and one cohort
      study) were carried out in India, Sweden and Nepal. The studies included women
      with gestational ages up to 14 weeks for surgical abortion and nine weeks for
      medical abortion.Risk of selection bias was considered to be low in the three
      RCTs, unclear in four observational studies and high in one observational study.
      Concealment bias was considered to be low in the three RCTs and high in all five
      observational studies. Although none of the eight studies performed blinding of
      the participants to the provider type, we considered the performance bias to be
      low as this is part of the intervention. Detection bias was considered to be high
      in all eight studies as none of the eight studies preformed blinding of the
      outcome assessment. Attrition bias was low in seven studies and high in one, with
      over 20% attrition. We considered six studies to have unclear risk of selective
      reporting bias as their protocols had not been published. The remaining two
      studies had published their protocols. Few other sources of bias were found.Based
      on an analysis of three cohort studies, the risk of surgical abortion failure was
      significantly higher when provided by mid-level providers than when procedures
      were administered by doctors (RR 2.25, 95% CI 1.38 to 3.68), however the quality
      of evidence for this outcome was deemed to be very low. For surgical abortion
      procedures, we found no significant differences in the risk of complications
      between mid-level providers and doctors (RR 0.99, 95% CI 0.17 to 5.70 from RCTs;
      RR 1.38, 95% CI 0.70 to 2.72 from observational studies). When we combined the
      data for failure and complications for surgical abortion we found no significant
      differences between mid-level providers and doctors in both the observational
      study analysis (RR 1.36, 95% CI 0.86 to 2.14) and the RCT analysis (RR 3.07, 95%
      CI 0.16 to 59.08). The quality of evidence of the outcome for RCT studies was
      considered to be low and for observational studies very low. For medical abortion
      procedures the risk of failure was not different for mid-level providers or
      doctors (RR 0.81, 95% CI 0.48 to 1.36 from RCTs; RR 1.09, 95% CI 0.63 to 1.88
      from observational studies). The quality of evidence of this outcome for the RCT
      analysis was considered to be high, although the quality of evidence of the
      observational studies was considered to be very low. There were no complications
      reported in the three medical abortion studies. AUTHORS' CONCLUSIONS: There was
      no statistically significant difference in the risk of failure for medical
      abortions performed by mid-level providers compared with doctors. Observational
      data indicate that there may be a higher risk of abortion failure for surgical
      abortion procedures administered by mid-level providers, but the number of
      studies is small and more robust data from controlled trials are needed. There
      were no statistically significant differences in the risk of complications for
      first trimester surgical abortions performed by mid-level providers compared with
      doctors.

PMID- 26214845
TI  - Robotic versus Laparoscopic Approach in Colonic Resections for Cancer and Benign
      Diseases: Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: The aim of this systematic review and meta-analysis is to compare
      robotic colectomy (RC) with laparoscopic colectomy (LC) in terms of
      intraoperative and postoperative outcomes. MATERIALS AND METHODS: A systematic
      literature search was performed to retrieve comparative studies of robotic and
      laparoscopic colectomy. The databases searched were PubMed, Embase and the
      Cochrane Central Register of Controlled Trials from January 2000 to October 2014.
      The Odds ratio, Risk difference and Mean difference were used as the summary
      statistics. RESULTS: A total of 12 studies, which included a total of 4,148
      patients who had undergone robotic or laparoscopic colectomy, were included and
      analyzed. RC demonstrated a longer operative time (MD 41.52, P<0.00001) and
      higher cost (MD 2.42, P<0.00001) than did LC. The time to first flatus passage
      (MD -0.51, P = 0.003) and the length of hospital stay (MD -0.68, P = 0.01) were
      significantly shorter after RC. Additionally, the intraoperative blood loss (MD 
      16.82, P<0.00001) was significantly less in RC. There was also a significantly
      lower incidence of overall postoperative complications (OR 0.74, P = 0.02) and
      wound infections (RD -0.02, P = 0.03) after RC. No differences in the
      postoperative ileus, in the anastomotic leak, or in the conversion to open
      surgery rate and in the number of harvested lymph nodes outcomes were found
      between the approaches. CONCLUSIONS: The present meta-analysis, mainly based on
      observational studies, suggests that RC is more time-consuming and expensive than
      laparoscopy but that it results in faster recovery of bowel function, a shorter
      hospital stay, less blood loss and lower rates of both overall postoperative
      complications and wound infections.

PMID- 26214846
TI  - Est16, a New Esterase Isolated from a Metagenomic Library of a Microbial
      Consortium Specializing in Diesel Oil Degradation.
AB  - Lipolytic enzymes have attracted attention from a global market because they show
      enormous biotechnological potential for applications such as detergent
      production, leather processing, cosmetics production, and use in perfumes and
      biodiesel. Due to the intense demand for biocatalysts, a metagenomic approach
      provides methods of identifying new enzymes. In this study, an esterase
      designated as Est16 was selected from 4224 clones of a fosmid metagenomic
      library, revealing an 87% amino acid identity with an esterase/lipase (accession
      number ADM63076.1) from an uncultured bacterium. Phylogenetic studies showed that
      the enzyme belongs to family V of bacterial lipolytic enzymes and has sequence
      and structural similarities with an aryl-esterase from Pseudomonas fluorescens
      and a patented Anti-Kazlauskas lipase (patent number US20050153404). The protein
      was expressed and purified as a highly soluble, thermally stable enzyme that
      showed a preference for basic pH. Est16 exhibited activity toward a wide range of
      substrates and the highest catalytic efficiency against p-nitrophenyl butyrate
      and p-nitrophenyl valerate. Est16 also showed tolerance to the presence of
      organic solvents, detergents and metals. Based on molecular modeling, we showed
      that the large alpha-beta domain is conserved in the patented enzymes but not the
      substrate pocket. Here, it was demonstrated that a metagenomic approach is
      suitable for discovering the lipolytic enzyme diversity and that Est16 has the
      biotechnological potential for use in industrial processes. 

PMID- 26214847
TI  - Expression Profiles of Neuropeptides, Neurotransmitters, and Their Receptors in
      Human Keratocytes In Vitro and In Situ.
AB  - Keratocytes, the quiescent cells of the corneal stroma, play a crucial role in
      corneal wound healing. Neuropeptides and neurotransmitters are usually associated
      with neuronal signaling, but have recently been shown to be produced also by non
      neuronal cells and to be involved in many cellular processes. The aim of this
      study was to assess the endogenous intracellular and secreted levels of the
      neuropeptides substance P (SP) and neurokinin A (NKA), and of the
      neurotransmitters acetylcholine (ACh), catecholamines (adrenaline, noradrenaline
      and dopamine), and glutamate, as well as the expression profiles of their
      receptors, in human primary keratocytes in vitro and in keratocytes of human
      corneal tissue sections in situ. Cultured keratocytes expressed genes encoding
      for SP and NKA, and for catecholamine and glutamate synthesizing enzymes, as well
      as genes for neuropeptide, adrenergic and ACh (muscarinic) receptors. Keratocytes
      in culture produced SP, NKA, catecholamines, ACh, and glutamate, and expressed
      neurokinin-1 and -2 receptors (NK-1R and NK-2R), dopamine receptor D2, muscarinic
      ACh receptors, and NDMAR1 glutamate receptor. Human corneal sections expressed
      SP, NKA, NK-1R, NK-2R, receptor D2, choline acetyl transferase (ChAT), M3, M4 and
      M5 muscarinic ACh receptors, glutamate, and NMDAR1, but not catecholamine
      synthesizing enzyme or the alpha1 and beta2 adrenoreceptors, nor M1 receptor. In
      addition, expression profiles assumed significant differences between keratocytes
      from the peripheral cornea as compared to those from the central cornea, as well
      as differences between keratocytes cultured under various serum concentrations.
      In conclusion, human keratocytes express an array of neuropeptides and
      neurotransmitters. The cells furthermore express receptors for
      neuropeptides/neurotransmitters, which suggests that they are susceptible to
      stimulation by these substances in the cornea, whether of neuronal or non
      neuronal origin. As it has been shown that neuropeptides/neurotransmitters are
      involved in cell proliferation, migration, and angiogenesis, it is possible that
      they play a role in corneal wound healing. 

PMID- 26214848
TI  - Measuring Patient Adherence to Malaria Treatment: A Comparison of Results from
      Self-Report and a Customised Electronic Monitoring Device.
AB  - BACKGROUND: Self-report is the most common and feasible method for assessing
      patient adherence to medication, but can be prone to recall bias and social
      desirability bias. Most studies assessing adherence to artemisinin-based
      combination therapies (ACTs) have relied on self-report. In this study, we use a
      novel customised electronic monitoring device--termed smart blister packs--to
      examine the validity of self-reported adherence to artemether-lumefantrine (AL)
      in southern Tanzania. METHODS: Smart blister packs were designed to look
      identical to locally available AL blister packs and to record the date and time
      each tablet was removed from packaging. Patients obtaining AL at randomly
      selected health facilities and drug stores were followed up at home three days
      later and interviewed about each dose of AL taken. Blister packs were requested
      for pill count and extraction of smart blister pack data. RESULTS: Data on
      adherence from both self-report verified by pill count and smart blister packs
      were available for 696 of 1,204 patients. There was no difference between methods
      in the proportion of patients assessed to have completed treatment (64% and 67%,
      respectively). However, the percentage taking the correct number of pills for
      each dose at the correct times (timely completion) was higher by self-report than
      smart blister packs (37% vs. 24%; p<0.0001). By smart blister packs, 64% of
      patients completing treatment did not take the correct number of pills per dose
      or did not take each dose at the correct time interval. CONCLUSION: Smart blister
      packs resulted in lower estimates of timely completion of AL and may be less
      prone to recall and social desirability bias. They may be useful when data on
      patterns of adherence are desirable to evaluate treatment outcomes. Improved
      methods of collecting self-reported data are needed to minimise bias and maximise
      comparability between studies.

PMID- 26214849
TI  - Characteristics and Propagation of Airgun Pulses in Shallow Water with
      Implications for Effects on Small Marine Mammals.
AB  - Airguns used in seismic surveys are among the most prevalent and powerful
      anthropogenic noise sources in marine habitats. They are designed to produce most
      energy below 100 Hz, but the pulses have also been reported to contain medium-to
      high frequency components with the potential to affect small marine mammals,
      which have their best hearing sensitivity at higher frequencies. In shallow water
      environments, inhabited by many of such species, the impact of airgun noise may
      be particularly challenging to assess due to complex propagation conditions. To
      alleviate the current lack of knowledge on the characteristics and propagation of
      airgun pulses in shallow water with implications for effects on small marine
      mammals, we recorded pulses from a single airgun with three operating volumes (10
      in3, 25 in3 and 40 in3) at six ranges (6, 120, 200, 400, 800 and 1300 m) in a
      uniform shallow water habitat using two calibrated Reson 4014 hydrophones and
      four DSG-Ocean acoustic data recorders. We show that airgun pulses in this
      shallow habitat propagated out to 1300 meters in a way that can be approximated
      by a 18log(r) geometric transmission loss model, but with a high pass filter
      effect from the shallow water depth. Source levels were back-calculated to 192 dB
      re uPa2s (sound exposure level) and 200 dB re 1 uPa dB Leq-fast (rms over 125 ms
      duration), and the pulses contained substantial energy up to 10 kHz, even at the
      furthest recording station at 1300 meters. We conclude that the risk of causing
      hearing damage when using single airguns in shallow waters is small for both
      pinnipeds and porpoises. However, there is substantial potential for significant
      behavioral responses out to several km from the airgun, well beyond the commonly
      used shut-down zone of 500 meters. 

PMID- 26214850
TI  - Effects of Radiation on Spinal Dura Mater and Surrounding Tissue in Mice.
AB  - PURPOSE: Spinal surgery in a previously irradiated field carries increased risk
      of perioperative complications, such as delayed wound healing or wound infection.
      In addition, adhesion around the dura mater is often observed clinically.
      Therefore, similar to radiation-induced fibrosis--a major late-stage radiation
      injury in other tissue--epidural fibrosis is anticipated to occur after spinal
      radiation. In this study, we performed histopathologic assessment of
      postirradiation changes in the spinal dura mater and peridural tissue in mice.
      MATERIALS AND METHODS: The thoracolumbar transition of ddY mice was irradiated
      with a single dose of 10 or 20 Gy. After resection of the irradiated spine,
      occurrence of epidural fibrosis and expression of transforming growth factor beta
      1 in the spinal dura mater were evaluated. In addition, microstructures in the
      spinal dura mater and peridural tissue were assessed using an electron
      microscope. RESULTS: In the 20-Gy irradiated mice, epidural fibrosis first
      occurred around 12 weeks postirradiation, and was observed in all cases from 16
      weeks postirradiation. In contrast, epidural fibrosis was not observed in the
      nonirradiated mice. Compared with the nonirradiated mice, the 10- and 20-Gy
      irradiated mice had significantly more overexpression of transforming growth
      factor beta 1 at 1 week postirradiation and in the late stages after irradiation.
      In microstructural assessment, the arachnoid barrier cell layer was thinned at 12
      and 24 weeks postirradiation compared with that in the nonirradiated mice.
      CONCLUSION: In mice, spinal epidural fibrosis develops in the late stages after
      high-dose irradiation, and overexpression of transforming growth factor beta 1
      occurs in a manner similar to that seen in radiation-induced fibrosis in other
      tissue. Additionally, thinning of the arachnoid barrier cell layer was observed
      in the late stages after irradiation. Thus, consideration should be given to the
      possibility that these phenomena can occur as radiation-induced injuries of the
      spine.

PMID- 26214851
TI  - Not Just the Demographic Change--The Impact of Trends in Risk Factor Prevalences
      on the Prediction of Future Cases of Myocardial Infarction.
AB  - BACKGROUND: Previous predictions of population morbidity consider demographic
      changes only. To model future morbidity, however, changes in prevalences of risk
      factors should be considered. We calculated the number of incident cases of first
      myocardial infarction (MI) in Mecklenburg-Western Pomerania in 2017 considering
      the effects of demographic changes and trends in the prevalences of major risk
      factors simultaneously. METHODS: Data basis of the analysis were two population
      based cohorts of the German Study of Health in Pomerania (SHIP-baseline [1997
      2001] and the 5-year follow-up and SHIP-Trend-baseline [2008-2011] respectively).
      SHIP-baseline data were used to calculate the initial coefficients for major risk
      factors for MI with a Poisson regression model. The dependent variable was the
      number of incident cases of MI between SHIP-baseline and SHIP-5-year follow-up.
      Explanatory variables were sex, age, a validated diagnosis of hypertension and/or
      diabetes, smoking, waist circumference (WC), increased blood levels of
      triglycerides (TG) and low-density-lipoprotein cholesterol (LDL), and low blood
      levels of high-density-lipoprotein cholesterol (HDL). Applying the coefficients
      determined for SHIP baseline to risk factor prevalences, derived from the new
      cohort SHIP-Trend together with population forecast data, we calculated the
      projected number of incident cases of MI in 2017. RESULTS: Except for WC and
      smoking in females, prevalences of risk factors in SHIP-Trend-baseline were lower
      compared to SHIP-baseline. Based on demographic changes only, the calculated
      incidence of MI for 2017 compared to the reference year 2006 yields an increase
      of MI (males: +11.5%, females: +8.0%). However, a decrease of MI (males: -23.7%,
      females: -17.1%) is shown considering the changes in the prevalences of risk
      factors in the projection. CONCLUSIONS: The predicted number of incident cases of
      MI shows large differences between models with and without considering changes in
      the prevalences of major risk factors. Hence, the prediction of incident MI
      should preferably not only be based on demographic changes.

PMID- 26214852
TI  - Training of upper respiratory endoscopy in the horse using preserved head and
      neck.
AB  - Endoscopy of the upper respiratory tract (URT) is one of the minimally invasive
      techniques used for diagnosis and treatment of diseases in horses. Training in
      the use of an endoscope follows an apprenticeship approach, with extensive
      practice needed to help achieve effective skills acquisition. The use of live
      animals for training presents the risk of injury to both the animal and the
      trainee. The increased number of students and practitioners, a shortage of
      facilities, and limited time available from expert clinicians add more challenges
      to the training process. In this work, we focused on the development of a
      preserved head and neck model that can be used as an effective training tool for
      training novices on the basics of upper respiratory endoscopy. The aim of the
      training is to become familiar with handling the endoscope and identification of
      the endoscopic depictions of normal anatomical structures encountered in the
      upper respiratory tract. Using the model, anatomical structures were clearly
      visible, recognized by their shape, architecture and topographical location. The
      model solved many of the aforementioned practical challenges, and has great
      potential as a replacement alternative to the use of live animals. There are
      opportunities for the application of such models intraining other clinical skills
      and for a variety of species.

PMID- 26214853
TI  - Impact of Adjuvant Chemotherapy on Breast Cancer Survival: A Real-World
      Population.
AB  - BACKGROUND: The impact of adjuvant chemotherapy on breast cancer prognosis has
      been demonstrated in randomized trials, but its impact is unknown in real-world
      populations. The aim of this study was to evaluate the effect of adjuvant
      chemotherapy on the survival of breast cancer patients in an unselected
      population. METHODS: This prospective cohort study included 32,502 women treated
      at the Institut Curie between 1981 and 2008 for a first invasive breast cancer
      without metastasis. The patients were matched based on their propensity score to
      receive adjuvant chemotherapy. RESULTS: The matching generated a subsample of
      9,180 patients with an overlapping propensity score. In the group without
      chemotherapy, the overall survival (OS) rates at 5 and 10 years of follow-up were
      87.6% (95% CI [86.7-88.6]) and 75.0% (95% CI [73.6-76.5]), respectively, versus
      92.1% (95% CI [91.3-92.9]) and 81.9% (95% CI [80.6-83.2]), respectively, in the
      chemotherapy group. Distant disease-free survival (DDFS) was significantly
      improved in the five first years (absolute benefit of 3.5%). In a multivariate
      analysis, adjuvant chemotherapy was associated with better OS (HR = 0.75, 95% CI
      [0.69-0.83], p<0.0001) and DDFS (HR = 0.82, 95% CI [0.75-0.90], p<0.0001).
      CONCLUSION: Adjuvant chemotherapy significantly improves OS and DDFS rates in an
      unselected population, in accordance with previous results reported by randomized
      trials.

PMID- 26214854
TI  - Detecting Subtle Shifts in Ecosystem Functioning in a Dynamic Estuarine
      Environment.
AB  - Identifying the effects of stressors before they impact ecosystem functioning can
      be challenging in dynamic, heterogeneous 'real-world' ecosystems. In aquatic
      systems, for example, reductions in water clarity can limit the light available
      for photosynthesis, with knock-on consequences for secondary consumers, though in
      naturally turbid wave-swept estuaries, detecting the effects of elevated
      turbidity can be difficult. The objective of this study was to investigate the
      effects of shading on ecosystem functions mediated by sandflat primary producers
      (microphytobenthos) and deep-dwelling surface-feeding macrofauna (Macomona
      liliana; Bivalvia, Veneroida, Tellinidae). Shade cloths (which reduced incident
      light intensity by ~80%) were deployed on an exposed, intertidal sandflat to
      experimentally stress the microphytobenthic community associated with the
      sediment surface. After 13 weeks, sediment properties, macrofauna and fluxes of
      oxygen and inorganic nutrients across the sediment-water interface were measured.
      A multivariate metric of ecosystem function (MF) was generated by combining flux
      based response variables, and distance-based linear models were used to determine
      shifts in the drivers of ecosystem function between non-shaded and shaded plots.
      No significant differences in MF or in the constituent ecosystem function
      variables were detected between the shaded and non-shaded plots. However, shading
      reduced the total explained variation in MF (from 64% in non-shaded plots to 15%
      in shaded plots) and affected the relative influence of M. liliana and other
      explanatory variables on MF. This suggests that although shade stress may shift
      the drivers of ecosystem functioning (consistent with earlier investigations of
      shading effects on sandflat interaction networks), ecosystem functions appear to
      have a degree of resilience to those changes. 

PMID- 26214855
TI  - MnO(x) Nanoparticle-Dispersed CeO2 Nanocubes: A Remarkable Heteronanostructured
      System with Unusual Structural Characteristics and Superior Catalytic
      Performance.
AB  - Understanding the interface-induced effects of heteronanostructured catalysts
      remains a significant challenge due to their structural complexity, but it is
      crucial for developing novel applied catalytic materials. This work reports a
      systematic characterization and catalytic evaluation of MnOx nanoparticle
      dispersed CeO2 nanocubes for two important industrial applications, namely,
      diesel soot oxidation and continuous-flow benzylamine oxidation. The X-ray
      diffraction and Raman studies reveal an unusual lattice expansion in CeO2 after
      the addition of MnOx. This interesting observation is due to conversion of
      smaller sized Ce(4+) (0.097 nm) to larger sized Ce(3+) (0.114 nm) in cerium oxide
      led by the strong interaction between MnOx and CeO2 at their interface. Another
      striking observation noticed from transmission electron microscopy, high angle
      annular dark-field scanning transmission electron microscopy, and electron energy
      loss spectroscopy studies is that the MnOx species are well-dispersed along the
      edges of the CeO2 nanocubes. This remarkable decoration leads to an enhanced
      reducible nature of the cerium oxide at the MnOx/CeO2 interface. It was found
      that MnOx/CeO2 heteronanostructures efficiently catalyze soot oxidation at lower
      temperatures (50% soot conversion, T50 ~660 K) compared with that of bare CeO2
      nanocubes (T50 ~723 K). Importantly, the MnOx/CeO2 heteronanostructures exhibit a
      noticeable steady performance in the oxidation of benzylamine with a high
      selectivity of the dibenzylimine product (~94-98%) compared with that of CeO2
      nanocubes (~69-91%). The existence of a strong synergistic effect at the
      interface sites between the CeO2 and MnOx components is a key factor for
      outstanding catalytic efficiency of the MnOx/CeO2 heteronanostructures. 

PMID- 26214856
TI  - THE CHERNOBYL ACCIDENT, THE MALE TO FEMALE RATIO AT BIRTH AND BIRTH RATES.

PMID- 26214857
TI  - The Chernobyl accident, the male to female ratio at birth and birth rates.

PMID- 26214858
TI  - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)/TRICARE:
      TRICARE Pharmacy Benefits Program. Final rule.
AB  - This final rule implements new authority for an over-the-counter (OTC) drug
      program, makes several administrative changes to the TRICARE Pharmacy Benefits
      Program regulation in order to conform it to the statute, and clarifies some
      procedures regarding the operation of the uniform formulary. Specifically, the
      final rule: Provides implementing regulations for the OTC drug program that has
      recently been given permanent statutory authority; conforms the pharmacy program
      regulation to the statute (including recent statutory changes contained in the
      Carl Levin and Howard P. "Buck" McKeon National Defense Authorization Act for
      Fiscal Year 2015) regarding point-of-service availability of non-formulary drugs
      and copayments for all categories of drugs; clarifies the process for formulary
      placement of newly approved drugs; and clarifies several other uniform formulary
      practices.

PMID- 26214859
TI  - Developmental Disabilities Program. Final rule.
AB  - This rule implements the Developmental Disabilities Assistance and Bill of Rights
      Act of 2000. The previous regulations were completed in 1997 before the current
      law was passed. The rule will align the regulations and current statute and will
      provide guidance to AIDD grantees.

PMID- 26214860
TI  - Chronic Kidney Diseases - Recent Advances in Clinical and Basic Research.
      Preface.

PMID- 26214861
TI  - TRICHLOROETHYLENE, TETRACHLOROETHYLENE, AND SOME OTHER CHLORINATED AGENTS.

PMID- 26214862
TI  - [Preparation Technique of Tetraploid of Dioscorea zingiberensis Synthetic Seed
      Based on Embryogenic Callus].
AB  - OBJECTIVE: To provide technical support for industrialization promotion of
      tetraploid of Dioscorea zingiberensis, the manufacturing method for synthetic
      seeds of tetraploid of Dioscorea zingiberensis was established and the correlated
      influential factors were studied. METHODS: By taking embryogenic calluses of
      tetraploid of Dioscorea zingiberensis as propagation materials, the influential
      factors such as components of artificial endosperm, seed coats,storage conditions
      and germination materials on germination and seedling of the synthetic seeds were
      evaluated. RESULTS: When 4% alginate +2% CaCl2 + 2% chitosan was served as seed
      coat materials, and 1/2 MS +0. 2 mg/L BA +0. 5 mg/L NAA + 0. 1 mg/L penicillin +
      0. 3% carhendazim powder + 0. 2% sodium benzoate + 1. 0% sucrose + 0. 5%
      activated carbon + 1. 0% tapioca starch was served as endosperm, the synthetic
      seeds had high germination rate and seedling rate. After storing at 4  degrees C
      for 20 d, the germination rate and seedling rate of synthetic seeds was 76. 7%
      and 71. 7%, respectively. CONCLUSION: Manufacturing technology of synthetic seeds
      of tetraploid of Dioscorea zingiberensis with embryogenic calluses as propagation
      materials has production prospects.

PMID- 26214863
TI  - [Biological and Phenological Properties of Salvia miltiorrhiza f. alba for Anti
      continuous Cropping].
AB  - OBJECTIVE: Morphological characteristics and phenological phase of Salvia
      miltiorrhiza f. alba for anti-continuous cropping was studied in the field.
      METHODS: The data of fixed plants of different stages were collected and
      analyzed. RESULTS: The resistance of the strains for anti-continuous cropping was
      obviously higher than the others. The phenological phase of strains for anti
      continuous cropping was divided into seedling stage, elongation stage,flower
      stage, fructification stage,root enlargement stage and dead stage. The whole
      development period was divided into the vegetative growth and reproduction growth
      by the flower stage. CONCLUSION: From the appearance characteristics and
      resistance observation, the growth of Salvia miltiorrhiza f. dlba for anti
      continuous cropping was better than the other strains in the next year.

PMID- 26214864
TI  - [Effects of Aphid Occurring on Lonicera macranthoides Bud Yield and Quality].
AB  - OBJECTIVE: To study the effects of aphid occurring on the quality of Lonicera
      macranthoides bud. METHODS: The fresh and dry bud yields of different aphid
      damage in the same plant were caculated. Contents of chlorogenic acid caffeic
      acid, luteolin-7-O-gluco-side, isochlbrogenic acid A, macranthoidin B and
      dipsacoside B in Lonicera macranthoides bud damaged by aphid were determined by
      HPLC-ELSD. RESULTS: Aphid significantly affected the contents of luteolin-7-O
      glucoside, macranthoidin B, dipsacoside B, and chlorogenic acid (P < 0. 01 or P
      <0. 05), but had no obvious effect on the content of caffeic acid and
      isochlorogenic acid A in the bud of Lonicera macranthoides. CONCLUSIONS: It is
      supposed to regulate prevention and control of aphids in Lonicera macranthoides
      GAP base.

PMID- 26214865
TI  - [Effect of Water Extracts from Rhizosphere Soil of Cultivated Astragalus
      membranaceus var. mongholicus on It's Seed Germination and Physiological
      Characteristics].
AB  - OBJECTIVE: To explore the relationship between continuous cropping obstacle and
      autotoxicity of Astragalus membranaceus var. mongholicus. METHODS: Distilled
      water(CK), water extracts of rhizosphere soil(50, 100, 200 and 400 mg/mL) were
      applied to test their effect on early growth and physiological characteristics of
      Astragalus membranaceus var. mongholicus. RESULTS: The water extracts from
      rhizospher soil of cultivated Astragalus membranaceus var. mongholicus
      significantly increased seedling emergence rate, root length and vigor index of
      Astragalus membranaceus var. mongholicus seedling when at the concentration of
      100 mg/mL or below, however,there was no significant effect at 200 mg/mL or
      higher. The water extracts from rhizosphere soil of cultivated Astragalus
      membranaceus var. mongholicus significantly reduced the SOD activity in
      Astragalus membranaceus var. mongholicus seedling at 400 mg/mL and POD activity
      at 200 mg/mL and 400 mg/mL,while significantly increased the MDA content.
      CONCLUSION: Water extracts from Astragalus membranaceus var. mongholicus
      rhizosphere soil significantly affected Astragalus membranaceus var. mongholicus
      germination and seedling growth in a concentration-dependent manner, generally,
      low concentrations increased the SOD and POD activity which improved seed
      germination and seedling growth, while high concentrations caused cell membrane
      damage of the seedling.

PMID- 26214866
TI  - [Characterization of Aldoses in Edible Bird's Nest from Southeast Asia by Gas
      Chromatography].
AB  - OBJECTIVE: To develop a method for the determination of aldoses in edible bird' s
      nest (EBN) from Southeast Asia. METHODS: Firstly, the sample was hydrolyzed by 2
      mol/L HCl-methanol, neutralized by 2 mol/L potassium hydroxide methanol solution,
      and acetylated by acetic anhydride in pyridine. Then, four aldoses were separated
      completely with HP-5 capillary chromatogram column,by using FID tester, through
      programmed temperature. RESULTS: The EBN's GC spectrum was significantly
      different from its adulterants. CONCLUSION: The GC method is characteristic,
      simple and reliable, which can be used to control the quality of EBN.

PMID- 26214867
TI  - [Analysis and Evaluation of Inorganic Elements in Euryale Semen from Different
      Habitats by Microwave Digestion-ICP-OES].
AB  - OBJECTIVE: To establish a simple, rapid and efficient method for determination of
      different inorganic elements in Euryale Semen from different habitats. METHODS:
      Inductively coupled plasma-optical emission spectrometry(ICP-OES) was applied to
      determine inorganic elements in Euryale Semen, and the results were analyzed by
      principal component analysis. RESULTS: Euryale Semen from different habitats
      contained the kind of inorganic elements ranging from 22 to 26, including
      micronutrient elements like Iron, Zinc, Selenium, Copper, Molybdenum, Chrome and
      Cobalt, as well as macronutrient elements such as Potassium, Calcium, Sodium,
      Magnesium and Phosphorus. Five factors were extracted and used to comprehensively
      evaluate Euryale Semen from 20 different habitats covered almost China. The
      comprehensive function was F = 0. 38828F1 + 0. 25603F2 + 0. 07617F3 + 0. 06860F4
      + 0. 04868F5, which resulted in the top three samples coming from Jiangsu Gaoyou,
      Hunan Xiangxi and Jiangsu Suzhou respectively. CONCLUSION: The study indicates
      that ICP-OES is a quick, accurate and sensitive method to determine the contents
      of inorganic elements in Euryale Semen,which provides scientific and reliable
      reference for its quality control and safety assessment.

PMID- 26214868
TI  - [Assay of Tetramethylpyrazine in Szechwan Lovage Rhizome and Cnidium Rhizome by
      HPLC-DAD-MS].
AB  - OBJECTIVE: To quantity the amount of tetramethylpyrazine in Szechwan Lovage
      Rhizome (Chuanxiong, the rhizome of Ligusticum chuanxiong Hort., CX) and Cnidium
      Rhizome(Japanese Chuanxiong, the rhizome of Cnidium officinale Makino, JCX) for
      quality assessment. METHODS: An HPLC-DAD-MS technique was employed to detect
      tetramethylpyrazine in 27 CX and 10 JCX samples. Tetramethylpyrazine was
      separated on a Waters Symmetry C,, column (250 mm x 4. 6 mm, 5 um). The mobile
      phase was methanol-acetonitrile-water(27: 1: 72) at a flow rate of 1. 0 mL/min.
      The column temperature was 35  degrees C. DAD detection wavelength was 280 nm,
      while electrospray ionization detector was set at positive mode to collect MS
      spectrum. RESULTS: In the total of 37 herb samples, 11 samples were found to
      contain tetramethylpyrazine with the mean amount of 2. 19 ug/g(n = 11). 6 of 27
      CX samples and 5 of 10 JCX sample were found the existence of tetramethylpyrazine
      with the amount of 0. 60 - 11. 75 ug and 0. 61 - 3. 05 ug/g,respectively. The
      correlation was not found between tetramethylpyrazine and the cultivation area,
      morphological character, processing or storage method for CX and JCX samples. It
      was possible that tetramethylpyrazine resulted from the microbes in soil.
      CONCLUSION: The developed method is accurate to quantify tetramethylpyrazine in
      CX and JCX herbs. Both the two herbs indeed contain tetramethylpyrazine, but it
      is not suitable to be a chemical marker to assess the quality of CX and JCX owing
      to low content.

PMID- 26214869
TI  - [Study on Precursors for Synthesis of Anthraquinone Metabolites from Rheum
      tanguticum].
AB  - OBJECTIVE: To explore the potential precursors of the anthraquinone metabolites
      from Rheum tanguticum and preliminanly identify the synthesis pathway thereof.
      METHODS: Sterile seedlings sprouted from the seeds of Rheum tanguticum were
      chosen as materials for inducing callus. The effects of different precursors and
      feeding duration on the callus of Rheum tanguticum and the anthraquinone yield in
      adult rheum were studied. RESULTS: The greatest improvement of anthraquinone
      yield was achieved by acetic acid, increasing 43. 9% for the callus and 45. 8% in
      the adult rheum; the second greatest improvement was achieved by malonic acid,
      increasing 15. 8% for the callus and only 3. 6% in the adult rheum. The yield of
      anthraquinone was not influenced significantly by benzoic acid and p
      benzoquinone, and in contrast, was inhibited in some degree by shikimic acid and
      alpha-ketoglutaric acid. A suitable feeding duration was 36 h, which worked well
      for the effects of precursors. CONCLUSION: The precursor for synthesis of
      anthraquinone metabolites from Rheum tan- guticum is acetic acid, which improves
      the yields of callus and anthraquinone in adult rheum, concluding that the
      anthraquinone metabolites are synthesized via polyketone pathway.

PMID- 26214870
TI  - [Effects of Wine-processing on Rhei Radix et Rhizoma on Upper-energizer Disease
      and Effects on Activities of Energy Metabolism Enzymes in Liver].
AB  - OBJECTIVE: To compare the effects of crude and wine-processed Rhei Radix et
      Rhizoma on upper-energizer disease and hepatic energy metabolism in mice.
      METHODS: The streptococcal pneumonia rats model and acetic acid burning mouth
      ulcers rats model were established and randomly divided into three groups: model
      group, crude Rhei Radix et Rhizoma group and wine-processed Rhei Radix et Rhizoma
      group. The pathologic changes were observed after the rats had been administrated
      with water extracts of crude and wine-processed Rhei Radix et Rhizoma
      respectively. The normal ICR mice were randomly divided into three groups:
      control group, crude Rhei Radix et Rhizoma group and wine-processed Rhei Radix et
      Rhizoma group. The influence of water extracts of crude and wine-processed Rhei
      Radix et Rhizoma on the activities of Na+, K-ATPase, Ca2+ -ATPase and succinic
      dehydrogenase(SDH) in the mice were compared. RESULTS: Compared with the crude
      one,the wine-processed Rhei Radix et Rhizoma significantly decreased the
      inflammation scores (P <0. 05), and promoted the tissue repair of acetic acid
      burning mouth ulcers rats model. The wine-processed one could also obviously
      reduce and normalize the level of leucocyte and neutrophilic granulocyte, lower
      the TNF-alpha level (P <0. 05), and relieve inflammatory exudation of the lung
      tissue. The inhibitory effects of wine-processed Rhei Radix et Rhizoma on the
      activities of SDH, Ca2+-ATPase and Na+, K + -ATPase were weaker than those of the
      crude one (P > 0. 05). CONCLUSION: After having been processed with wine, the
      efficacy of Rhei Radix et Rhizoma on upper-energizer disease is enhanced, and the
      inhibition on the activity of energy metabolism enzyme in liver tends to be
      weakened.

PMID- 26214871
TI  - [Study on HPLC Fingerprint of Trichosanthes Fruit and Its Processed Products].
AB  - OBJECTIVE: To study the correlation on chemical fingerprint features between
      Trichosanthis Fructus and its processed products. METHODS: The chemical
      fingerprints were established by HPLC for the ethyl acetate extraction and the n
      butanol extraction in Trichosanthis Fructus and its processed products,the common
      pattern was established by the mean and the median, and the similarity degree
      between Trichosanthis Fructus and its processed products was calculated by the
      correlation coefficient method and the included angle cosine method. RESULTS:
      There were 24 common peaks in the fingerprints of ethyl acetate extraction of
      Trichosanthis Fructus and its processed products,the average similarity degree
      was calculated separately by the correlation coefficient method and the included
      angle cosine method:the former as the value was 0. 8497(mean), 0. 8344(median);
      and the latter as the value was 0. 8429(mean), 0. 8536 (median); there were 6
      common peaks in the fingeprints of n-butanol extraction of Trichosanthis Fructus
      and its processed products, the average similarity degree was calculated by the
      correlation coefficient method and the included angle cosine method:the former as
      the value was 0. 9044 (mean), 0. 9076 (median); and the latter as the value was
      0. 9075 (mean), 0. 9081 (median). CONCLUSION: Main peaks have good correlation
      between Trichosanthis Fructus and its processed products. This method can provide
      theoretical basis for processing and quality control of Trichosanthis Fructus.

PMID- 26214872
TI  - [Study on Identification of Three Medicinal Plant Leaves from Elaeagnus Genus by
      Infrared Spectroscopy].
AB  - OBJECTIVE: To study and identify the three species of dry medicinal plant leaves
      trom Elaeagnus genus (E. pungens, E. lanceolata and E. henryi) by Infrared
      Spectroscopy(IR). METHODS: Fourier transform infrared spectroscopy and second
      derivative infrared spectroscopy were used to study and compare the
      characteristics of leaves of three Elaeagnus medicinal plants. RESULTS: The IR
      spectra and second derivative infrared spectra of the three Elaeagnus plants
      leaves were similar on the whole, the intensity or ratio of intensity of some
      absorption peaks still had certain distinctions, and the differences of the
      second derivative infrared spectra were more obvious. There were only slight
      differences between large and small leaf type of samples of Elaeagnus lanceolata;
      the differences of the plant leaves of one species collected in different harvest
      periods were far smaller than those of others belonging to the same genus.
      CONCLUSION: IR can be relatively reliably used for identification of the three
      Elaeagnus leaves.

PMID- 26214873
TI  - [Study on Chemical Constituents of Kalimeris indica].
AB  - OBJECTIVE: To study the chemical constituents from the active fractions of
      Kalimeris indica. METHODS: The chemical constituents were extracted of different
      concentrations and isolated by silica gel, Sephadex LH-20 column and preparative
      HPLC. The chemical structures were further elucidated by the physicochemical
      characters, MS and NMR spectral data. RESULTS: Fourteen compounds were isolated
      and identified as alpha-spinasterol(1), dibutylphthalate (2), (22E,24R)
      5alpha,8alpha-epidioxy-ergosta-6,22-dien-3beta-ol(3), oleanolic acid(4),
      coniferyl alcohol(5), umbelliferone(6), syringaresinol(7), 15-oxo-14,16H-strictic
      acid(8), lariciresinol(9), (Z)-3,7,11-trimethyl-1,6-dodecadien-3,10,11-triol(10),
      neoechinulin A(11), pinoresinol(12), 4-allyl-3,5-dimethoxyphenol(13), and 3,4,5
      tri-methoxyacetophenone (14). CONCLUSION: Except compound 1, the other compounds
      are isolated from this genus for the first time.

PMID- 26214874
TI  - [Study on Chemical Constituents from Hypocotyls of Mangrove Bruguiera
      gymnorrhiza].
AB  - OBJECTIVE: To study the chemical constituents from the hypocotyls of mangrove
      Bruguiera gymnorrhiza. METHODS: The chemical constituents were isolated and
      purified by recrystallization, silica gel column chromatography and semi
      preparative HPLC. Their structures were identified by spectroscopic analysis and
      comparison with literatures. RESULTS: Seven compounds were isolated and their
      structures were identified as 3-beta-(Z)-coumaroyllupeol (1), dioslupecin (2),
      cholesterol (3), menisdaurillide (4), aquilegiolide (5) vomifoliol (6) and
      roseoside II (7). CONCLUSION: Compounds 1,2 and 4 - 7 are isolated from this
      plant for the first time.

PMID- 26214876
TI  - [Study on Chemical Constituents of Petroleum Ether Fraction from Rubus
      alceaefolius].
AB  - OBJECTIVE: To investigate the chemical constituents of Rubus alceaefolius.
      METHODS: Nine compounds were isolated and purified from the petroleum ether
      extract of 95% alcohol extract of Rubus alceaefolius by repeated column
      chromatography on silica, Sephadex LH-20 and structurally identified by spectral
      analysis. RESULTS: The compounds were identified as chrysophanol(1), physcion
      (2), beta-sitosterol(3), 3-oxotirucalla-7, 24-dien-21-oic acid(4), myricadiol(5),
      19-alpha-hydroxy-3-acetyl-ursolic acid(6), N-benzoylphenylalaninyl-N
      benzoylphenylalaninate(7), aurantiamide acetate(8) and euscaphic acid(9).
      CONCLUSION: Compounds land 4~8 are isolated from this plant for the first time,
      and compounds 4 - 8 are found in plants of Rubus genus for the first time.

PMID- 26214875
TI  - [Chemical Constituents with Anti-hypoxia Activity from Saussurea involucrata].
AB  - OBJECTIVE: To investigate the chemical constituents with anti-hypoxia activity
      from Saussurea involucrata. METHODS: The chemical constituents, isolated and
      purified by column chromatography from Saussurea involucrata, were identified by
      several spectroscopic methods. The anti-hypoxic activities of these compounds
      were examined using the normobaric hypoxic model of mice. RESULTS: Twelve
      compounds were isolated from petroleum ether extract of Saussurea involucrata and
      identified as n-octacosane (1), 1-undecanol (2), heptadecan-l-ol(3), heptacosan-1
      ol(4), myristicin (5), apiol(6), beta-sitosterol(7), lupeol(8), moslosooflavone
      (9), mosloflavone (10), negletein(11), and 5, 6-dihydroxy-7, 8
      dimethoxyflavone(12). CONCLUSION: All compounds except 7 and 8 are isolated from
      this plant for the first time. Compound 1, 5 and 8 - 12 can significantly prolong
      the survival time of hypoxic mice.

PMID- 26214877
TI  - [Chemical Constituents from Cynanchum paniculatum].
AB  - OBJECTIVE: To investigate the chemical constituents from Gynanchum paniculatum.
      METHODS: The constituents were isolated and purified by silica gel, Sephadex LH
      20 column chromatography, and preparative TLC. Their structures were identified
      on the basis of spectral data and physiochemical characteristics. RESULTS: 15
      compounds were isolated from 70% ethanol extract and identified as beta
      sitosterol(1), beta-daucosterin (2), mudanoside A (3), paeonolide (4), santamarin
      (5), paeonol(6), annobraine (7), laricircsinol (8), alpha-asarone(9), 7
      angelyheliotridine(10), beta-amyrin(11), uridine(12), kaempferol-3-O-beta-D
      glucopyranosyl(1->2)alpha-L-arabinopyranoside(13), kaempferol-7-O-(4", 6"-di-p
      hydroxycinnamoyl-2", 3"-diacetyl)-beta-D-glucopyranoside(14), and (2S, E)-N-[2
      hydroxy-2-(4-hydroxyphenyl) ethyl] ferulamide (15). CONCLUSION: Compounds 4, 6,
      8, 11, 12 and 15 are isolated from this plant for the first time, compounds 5 and
      14 are firstly isolated from the palnts of Cynanchum genus.

PMID- 26214878
TI  - [Phenylpropanoids from Saussureae hieracioides].
AB  - OBJECTIVE: To isolate and identify the phenylpropanoids from Saussurea
      hieracioides. METHODS: The compounds were isolated by chromatographic and their
      structures were elucidated on the basis of spectra data. RESULTS: Seven compounds
      were isolated and identified as umbelliferone (1), scopoletin(2), caffeic acid
      (3), esculetin (4), skimmin (5), scopolin (6) and chlorogenic acid (7),
      respectively. CONCLUSION: Compounds 3, 4 and 7 are isolated from this plant for
      the first time.

PMID- 26214879
TI  - [Protective Effect of Polygonum orientale Flower Extract with Different
      Preparation Methods on Acute Myocardial Ischemia in Mongrel Dogs].
AB  - OBJECTIVE: To observe the effect of Polygonum orientale flower extract with
      different preparation methods on acute myocardial ischemia in mongrel dogs.
      METHODS: The acute myocardial ischemia model of dog was set up though ligation of
      anterior descending branch of coronary artery in dogs, then the epicardium
      electrocardiogram was used to measure the degree of myocardial ischemia and the
      quantitative histological assay was adopted to determine the area of myocardial
      ischemia. At the same time, the lactic dehydrogense (LDH) and creatine kinase(CK)
      levels in serum were analyzed. All of them were used to evaluate the protective
      effect of Polygonum orientale flower with different preparation methods on acute
      myocardial ischemia in mongrel dog. RESULTS: Compared with the model group, the
      sample whose preparation methods was extracted by n-butanol after water
      extracting and alcohol precipitation showed obvious reduction in the area of
      myocardial ischemia,with decline in ?ST and NST. Moreover,the LDH and CK levels
      in serum were decreased (P <0. 05 or P <0. 01). CONCLUSION: The sample which is
      extracted by n-butanol after water extracting and alcohol precipitation has a
      protective effect on injury induced by acute myocardial ischemia in mongrel dog.

PMID- 26214880
TI  - [Synthesis and Identification of Artificial Antigen of Mangiferin].
AB  - OBJECTIVE: To establish an enzyme linked immunosorbent assay(ELISA) for
      mangiferin (MRn), artificial antigen of MRn was synthesized. METHODS: Oxidation
      method using sodium iodide was used to synthesize immunogenic antigen (MRn-BSA)
      and coating antigen(MRn-OVA) of MRn. The characterization of the synthesis was
      examined by UV spectrometry. BALB/c mice were immunized with the prepared MRn-BSA
      immunogenic antigen. The titer of the anti-serum was detected by ELISA, in the
      meanwhile the immunogenicity of MRn-BSA was confirmed by indirect competitive
      ELISA (icELISA). RESULTS: UV spectroscopy showed that MRn was successfully
      conjugated with OVA and BSA,so the new compound of MRn-BSA was synthesized, the
      coupling ratio was 6: 1. After immuned MRn-BSA, the mice could produce anti-MRn
      antibodies specifically, of which titer was up to 1: 4 000, and the general range
      was 1 - 100 ug/mL. CONCLUSION: Anti-MRn antibodies are discovered in the serum of
      mice, which indicates that artificial antigen of MRn is successfully
      synthesized,for the purpose of preparing monoclonal antibodies, as well as the
      establishment of appropriate immune methods.

PMID- 26214881
TI  - [Effect of Qige Powder on Angiogenesis Induced by Esophageal Cancer Cell Line Eca
      9706].
AB  - OBJECTIVE: To study the effect Qige powder on esophageal cancer angiogenesis.
      METHODS: Inhibitive effect of Qige powder ethanol extract on proliferation of
      Esophageal cancer cell line Eca-9706 was detected by MTT assay. The Eca-9706
      cells conditioned medium in Qige powder IC50 concentration were collected.
      Angiogenesis, as well as proliferation, migration and tube formation of human
      umbilical vein endothelial cells were observed by Chick embryo chorioallantoic
      membrane model(CAM), MTT assay, the migration and tube formation assay. VEGF and
      IL-6 contents in culture medium supernatant of Eca-9706 cells and human umbilical
      vein endothelial cells were detected by ELISA. RESULTS: Qige powder ethanol
      extract could inhibit the proliferation of Eca-9706 cells, with a certain dose
      effect relationship, IC50 value was 96 ug/mL. Eca-9706 cells conditioned medium
      could significantly increase the CAM generating total vessel area, human
      umbilical vein endothelial cells proliferation,migration and tube formation,
      while the Eca-9706 cell conditioned medium of Qige powder ethanol extract could
      reduce CAM angiogenesis, human umbilical vein endothelial cells proliferation and
      tube formation, but increase endothelial cells migration. Qige powder ethanol
      extract could reduce endothelial cells secreting VEGF and IL-6 while increase Eca
      9706 cells secreting. CONCLUSION: Qige powder ethanol extract can inhibit
      angiogenesis, endothelial cell proliferation, and tube formation induced by Eca
      9706 cells, while reduce VEGF and IL-6 secretion of endothelial cells.

PMID- 26214882
TI  - [Extracts from Testudinis Carapacis et Plastri Regulates Expression of ID1 in
      Mscs].
AB  - OBJECTIVE: To explore BMP4 affecting the Extracts from Testudinis Carapacis et
      Plastri (PTE) stimulating proliferation of MSCs and the mechanism. METHODS:
      Cotransfected PGL3-IDI and pEGFP-BMP4 of 0, 0. 1,0. 3, 0. 5 and 1 ug/mL
      respectively using the calcium phosphate co-precipitation method in rat MSCs. One
      of transfected cells were divided into control group and PTE group. PTE group was
      stimulated by PTE of 30 u/L for 36 h, while control group was not. Collected
      cells using lucifease activity measurement to detect the activity of ID. Then 0.
      3 ug/mL pEGFP-BMP4 was chose to cotransfect. MSCs was divided into control group,
      PTE group, BMP4 group, BMP4 + PTE group. BMP4 and BMP4 + PTE group were
      cotransfected with PGL3-ID1 and pEGFP-BMP4 but control or PTE groups were not.
      PTE and BMP4 + PTE groups were stimulated by PTE of 30 ug/mL for 36 h but the
      either two groups were not. The activities of ID1, BMP4 and RARalpha were
      detected using RT-PCR. RESULTS: The expressions of ID1, BMP4 and RARa rose in PTE
      group. The expression of BMP4 and RARalpha rose while IDI decreased in BMP4
      groups. BMP4, ID1 and RARalpha decreased remarkable in BMP4 + PTE group comparing
      with BMP4 group. CONCLUSION: PTE promotes the proliferation of MSCs, it also
      regulates the expression of BMP4 to prevent excessive proliferation of MSCs.

PMID- 26214883
TI  - [Pharmacokinetics and Intestinal Absorption of Curcumin Chitosan Hydrochloride
      Coated Liposome in Rats].
AB  - OBJECTIVE: To investigate the pharmacokinetics and intestinal absorption
      characteristic of curcumin chitosan hydrochloride coated liposome(CCLP) in SD
      rats. METHODS: Blood samples were collected after oral administration.
      Pharmacokinetic parameters were analyzed by DAS program. Rat single pass
      intestinal perfusion method was employed to investigate the absorption mechanism.
      RESULTS: The AUC0-t, AUC0-infinity, t1/2, and Cmax of CCLP were 1. 73-fold, 1. 95
      fold, 1. 56-fold and 1. 91-fold of the free drug. The intestinal absorption rate
      constant (Ka) of CCLP in duodenum, jejunum, ileum and colon were 1. 48, 1. 28, 1.
      17 , and 4. 01 times as much as the free drug and the effective
      permeability(Peff) of CCLP were 1. 58, 1.-33, 1. 30 and 4. 55 times of the free
      drug, respectively. CONCLUSION: The bioavailability of CCLP in rats is increased
      remarkably and Ka is increased in various intestinal segments by CCLP, especially
      in colon, as well as Peff.

PMID- 26214884
TI  - [Simultaneous Determination of Five Astragalosides in Astragali Radix and Jinqi
      Jiangtang Tablet by HPLC-ELSD].
AB  - OBJECTIVE: To develop an HPLC-ELSD method for simultaneous determination of
      Astragaloside IV Astragaloside I, Astragaloside II, Astragaloside III and
      Isostragaloside II in Astragali Radix and Jinqi Jiangtang tablet. METHODS: The
      chromatographic conditions were as follows: Grace Apollo C18 column (250 mm x 4.
      6 mm, 5 um), acetonitrile (A) and water(B) as mobile phases for gradient elution,
      and the flow rate being 1. 0 mL/min. RESULTS: Five components showed good
      linearity. The average recoveries were between 95% - 105%. Five Astragalosides
      were determined in twelve batches of Astragali Radix and ten batches of Jinqi
      Jiangtang tablet. CONCLUSION: This is a specific, sensitive and simple method for
      simultaneous determination of Astragaloside IV, Astragaloside I Astragaloside II,
      Astragaloside III and Isostragaloside II in Astragali Radix and Jinqi Jiangtang
      tablet.

PMID- 26214885
TI  - [Study on Glycosides Constituents from Guangdong Liangcha Granules(II)].
AB  - OBJECTIVE: To study the glycosides from Guangdong Liangcha Granules. METHODS: The
      chemical constituents were isolated by various chromatographic techniques and the
      structures of chemical constituents were identified by spectroscopic analysis and
      literature. RESULTS: Six compounds were isolated and identified as ilexoside B
      (1), asprellanosides B (2), asprellanoside A (3), 4', 5 ,7 -tri- hydroxyflavone-6
      O-beta3-D-glucopyranosyl ester(4), isoviolanthin (5),3-O-methy-lellagic acid 4'-O
      rhamnopyranoside (6). CONCLUSION: Compounds 1 - 5 are firstly obtained from
      Guangdong Liangcha Granules.

PMID- 26214886
TI  - [Preparation of Curcumin Nanosuspensions and Its Pharmacokinetic Behavior in
      Rats].
AB  - OBJECTIVE: To prepare curcumin nanosuspensions (Cur-NS), and to study the
      pharmacokinetics of Cur-NS in rats. METHODS: Cur-NS was prepared by the high
      pressure homogenization technology. The particle size, PdI and Zeta electric
      potential of nanosuspensions were taken as the indexes to determinate the factors
      that influenced the preparation process greatly. Curcumin concentrations in
      plasma were determined by HPLC and the pharmacokinetic parameters were
      calculated. RESULTS: The particle size, polydisper- sion index, Zeta potential of
      Cur-NS were found to be 396. 4 +/- 67. 2 nm, 0. 369 +/- 0. 061 and -16.7 +/- 3. 5
      mV,respectively. AUC(0-t) of curcumin bulk drugs and Cur-NS were estimated to be
      3. 62 +/- 0. 66 mg/(L . h) and 14. 36 +/- 1. 20 mg/( L . h), half lifes(t1/2)
      were 0. 62 +/- 0. 06 h and 2. 15 +/- 0. 15 h tmax were 1. 83 +/- 0. 11 h and 1.
      02 +/- 0. 09 h, Cmax were 0. 94 +/- 0.12 mg/L and 5. 78 +/- 0. 46 mg/L,
      respectively. CONCLUSION: The pharmacokinetic results demonstrate that the
      curcumin bulk drugs prepared into Cur-NS can increase the drug's bioavailability
      in rats significantly.

PMID- 26214887
TI  - [Clinical Efficacy of Supplementary Treatment of Gukang Capsules to the Elder
      Patients with Fracture of Distal Radius].
AB  - OBJECTIVE: To study the clinical efficacy of supplementary treatment of tukang
      Capsules to the elder patients with fracture of the distal radius. METHODS: A
      total of 108 elder patients with fracture of the distal radius diagnosed by X
      ray,who visited orthopedics department of Pu' ai Hospital in January 2012 -
      December 2013, were randomly divided into observation group and control group.
      Cases in both groups received the operation of internal fixation by T-type plate.
      Cases in control group received oral Calcium Carbonate Tablets, and cases in
      observation group received Gukang Capsules besides Calcium Carbonate Tablets.
      Treatment duration was four weeks. The painful and swelling degree of wrist
      joints, levels of type I propeptide carboxy-terminal procollagen (P I CP) and
      bone glaprotein(BGP) in serum were compared. Hospitalization and fracture healing
      time, as well as recovery condition of wrist joints in the sixth month after
      operation were compared. RESULTS: The VAS of both groups was not significantly
      different before operation and in the 28th day after operation(P >0. 05), but the
      VAS in observation group was significantly lower than that in control group in
      the 3rd,5th, 7th, 14th and 21th day after operation(P <0. 01). The swelling scale
      of both groups was not significantly different before operation and in the 28th
      day after operation(P >0. 05), but the swelling scale in observation group was
      significantly lower than that in control group in the 3rd, 5th, 7th, 14th and
      21th day after operation(P <0. 01). The levels of P I CP and BGP in serum of both
      groups were not significantly different before operation(P >0. 05), but the
      levels of P I CP and BGP in serum of observation groups were significantly higher
      than that in control group one and two months after operation (P <0. 01).
      Hospitalization and fracture healing time in observation group was significantly
      shortened compared with control group (P <0. 05). The effective ratio in
      observation group was 79. 63%, significantly higher than that in control group (P
      <0. 05). CONCLUSION: Gukang Capsules supplementary to internal fixation by T-type
      plate has favorable efficacy to fracture of the distal radius, which can reduce
      pain and swelling, increase levels of P I CP and BGP in serum, as well as promote
      the heal of fracture and recovery of wrist joints function.

PMID- 26214888
TI  - [Progress in Eye Preserving Therapies for Retinoblastoma].

PMID- 26214889
TI  - [Clinical Research of Factors Influencing Visual Outcomes in Patients with
      Hemorrhagic Retinal Arterial Macroaneurysms].
AB  - PURPOSE: To identify factors influencing visual outcomes in patients with
      hemorrhagic retinal arterial macroaneurysms (MA). METHODS: We retrospectively
      reviewed the charts of 13 eyes of 13 patients with hemorrhagic MAs. We evaluated
      factors. including age, blood pressure, ocular perfusion pressure, optic disc-MA
      distance, MA-fovea distance, the area of the hemorrhage, the time between onset
      and treatment, initial visual acuity, and the presence of subfoveal hemorrhage.
      Additionally, we measured the retinal cross-sectional area of the fovea with
      optical coherence tomography (OCT). RESULTS: There were significant differences
      in MA-fovea distance, area of the subretinal hemorrhage, and visual outcome in
      eyes with or without subfoveal hemorrhage (p < 0.05). Spearman's correlation
      analysis showed a significant negative correlation between visual outcome
      (logMAR) and disc-MA distance (rS = -0.61, p < 0.05), as well as MA-fovea
      distance (rS = -0.79, p < 0.01). A multivariate analysis showed an independent
      negative correlation between visual outcome and MA-fovea distance (Stdbeta = 
      0.66, t = 3.21, p < 0.01). In addition, there was a significant positive
      correlation between MA-fovea distance and the affected-/healthy-eye ratio of
      outer-retinal-layer cross-sectional area in the fovea (rS = 0.64, p < 0.05). The
      cutoff value of MA-fovea distance for subfoveal hemorrhage was 3000 microns, with
      a sensitivity of 100, specificity of 77.8, positive predictive value of 66.7 and
      a negative predictive value of 100. CONCLUSIONS: When hemorrhagic MAs are located
      closer to the fovea, the outer retinal layer is more severely affected and visual
      outcomes are poorer. Subfoveal hemorrhage should be considered even when it is
      not apparent, especially when the hemorrhagic MA is located within 3000 microns
      of the fovea.

PMID- 26214890
TI  - [Analysis of Cytokines Related to Helper T and Regulatory T Cells in the Vitreous
      of Uveitis Patients].
AB  - PURPOSE: To investigate helper T (Th) cell-related cytokines elevated in the
      vitreous of endogenous uveitis (EU), and to compare these with those of acute
      retinal necrosis (ARN). METHODS: Vitreous fluids were obtained from 23 eyes of EU
      patients, 4 eyes of ARN patients, and 14 eyes of patients with epiretinal
      membrane (ERM) who had had vitrectomy surgery. The vitreous levels of interleukin
      (IL)-1, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL
      33, interferon (IFN)-gamma, soluble CD40 ligand (sCD40L) and tumor necrosis
      factor (TNF)-alpha were measured. RESULTS: The vitreous cytokine levels of IL-6,
      IL-10, IL-31, IFN-gamma and TNF-alpha in the EU patients were significantly
      higher than in the ERM patients. On the other hand, the levels of IL-1beta, IL-6,
      IL-10, IL-31, IFN-gamma, sCD40L and TNF-alpha were significantly higher in the
      ARN patients than in the EU patients, while those of IL-4, IL-17A and IL-22 were
      higher in the EU patients than in the ARN patients although they were not
      significant. CONCLUSIONS: It is suggested that Th1-, Th2- and Th17 cells are
      related to the development of EU, and Th1- and regulatory T cells to that of ARN,
      and that the severity of ocular inflammation may be associated with the activity
      of Th1 cells.

PMID- 26214891
TI  - [Incidence of Postoperative Retinal Detachment after 25-gauge Vitrectomy for
      Macular Diseases].
AB  - PURPOSE: To examine the rate of postoperative retinal detachment following 25
      gauge vitrectomy with extensive peripheral vitreous shaving in eyes with macular
      diseases. METHODS: A retrospective non-randomized study of 925 macular surgery
      cases was undertaken. All surgery was performed using 25-gauge vitrectomy and
      peripheral vitrectomy was done with scleral indentation. Epiretinal membrane
      (ERM) surgery (n = 523) and idiopathic macular hole (MH) surgery (n = 402) were
      performed between June 2005 and January 2014 by one surgeon (H. N.) and all cases
      were followed up for more than six months. We studied the rate of preexisting
      posterior vitreous detachment (PVD), endolaser treatment performed for retinal
      hole/tear and postoperative retinal detachment. RESULTS: Preexisting PVD was
      observed in 61.8% of eyes with ERM and in 10.7% of eyes with MH. The rate of
      endolaser treatment was 41.5% in ERM and 18.0% in MH cases, a statistically
      significant difference. Postoperative retinal detachment was seen in four of 925
      eyes (0.43%) overall. CONCLUSION: Extensive peripheral vitrectomy using scleral
      indentation reduced the incidence of postoperative detachment occurring after 25
      gauge macular surgery.

PMID- 26214892
TI  - [EFFICIENCY OF INTRODUCING CAROTENE PRODUCING STRAINS BACILLUS SP. 1.1 AND B.
      AMYLOLIQUEFACIENS UCM B-5113 INTO THE CHIKENS DIET].
AB  - It was shown the efficiency of carotene producing strains Bacillus sp. 1.1 and B.
      amyloliquefaciens UCM B-5113 in the diet of chickens. Also it was detected the
      lowering of the quantitative content of bacterial genera Enterococcus,
      Staphylococcus, family Enterobacteriaceae in the gut after eating by chickens
      cross "H&N Brown Nick" fodder with strains Bacillus sp. 1.1 and B.
      amyloliquefaciens UCM B-5113 alone and in composition in quantities 1 x 10(10)
      CFU per 1 g of feed. On the 18th day after introduction of cultures Bacillus sp.
      1.1, B. amyloliquefaciens UCM B-5113 and their composition in the diet of poultry
      we revealed the increasing of body weight by 21.6, 7.6 and 22.0%, respectively,
      comparesing to controls. Also due to Bacillus sp. 1.1 it was detected the restore
      of intestinal villous structures, tissues of spleen, liver and heart. We found
      the additive effect of the composition of the investigated strains of bacteria
      genus Bacillus to the chickens.

PMID- 26214893
TI  - [WET-MODE SCANNING ELECTRON MICROSCOPY AS AN INSTRUMENT FOR STUDIES OF
      BIOGEOCHEMICAL PROCESSES OF FUNGAL BIOMINERALS FORMATION].
AB  - The aim of this work was to examine the potential of the use of one of the modern
      approaches in scanning electron microscopy--the wet mode ESEM to study
      biogeochemical processes of biominerals formation by micromycetes. The object of
      the study was microscopic fungus Beauveria caledonica known for its ability to
      transform metals and minerals. In response to the presence of copper phosphate in
      the medium, it was observed the abundant formation of copper oxalate crystals in
      fungal mycelium. Optimal visualization at wet mode was achieved at the sample
      chamber pressure around 6 torr and relative humidity 85 - 90%. The comparison of
      the observations obtained using high-vacuum mode and wet mode scanning electron
      microscopy showed that in their natural state fungal hyphae and mycelial cords
      are surrounded by thick hydrated mucilaginous sheath which serves as a matrix for
      biogeochemical processes of secondary minerals formation and growth. The wet mode
      and high-vacuum mode scanning electron microscopies complement each other in
      comprehensive study of biogeochemical role of microscopic fungi in
      transformations of metals and minerals.

PMID- 26214894
TI  - [ABILITY OF MICROORGANISMS FROM DIFFERENT ECOLOGICAL NICHES TO HYDROLYZE THE
      INSOLUBLE PROTEINS].
AB  - Screening of protease producers with specificity to insoluble and hard soluble
      protein substrates of animal origin (collagen, fibrin, elastin and keratin) was
      carried out. It was studied the bacterial cultures (24 strains) isolated from
      water and periphyton of enclosures with dolphins, and also from exhalations, oral
      cavity and skin of dolphins. Some bacterial strains isolated from water and
      periphyton of enclosures hydrolyzed collagen (5-23 U/ml) and elastin (20-32
      U/ml). Thus all tested cultures did not possess the property of extracellular
      keratinases synthesis. The streptomycetes (48 strains) were isolated from the
      soil of Black Sea coastal strip near Odessa and Saky, from parkland and the
      shores of freshwater lake in Saky and from the soil of Atlantic Ocean coastal
      strip near Albufena (Portugal). Several streptomycetes have been found to appeare
      the perspective producers of extracellular keratinase and collagenase. The
      strains isolated from the soil of the coastal strip area both sea and freshwater
      lake in Saky possessed the highest activity (up to 5 U/mg).

PMID- 26214895
TI  - ANTIMICROBIAL ACTIVITY OF EXTRACTS FROM ECUADORIAN LICHENS.
AB  - Antimicrobial activity of the ethanolic, isopropanolic, acetone, DMSO and aqueous
      extracts of the two lichen species from Ecuadorian highland, Usnea sp. and
      Stereocaulon sp. were explored in vitro against bacteria Bacillus subtilis,
      Escherichia coli and Staphylococcus aureus by the disc-diffusion method. Also the
      minimal inhibitory concentration (MIC) was determined. The strongest
      antimicrobial activity was found in DMSO extract of Usnea sp. compared to
      antibacterial activity of ciprfloxacin and cefazolin antibiotics. The inhibition
      zone was 28 mm, 30 mm, 31mm (DMSO extract, ciprfloxacin and cefazolin
      respectively) in case of B. subtilis usage as the test bacteria. MIC value for
      Usnea sp. and Stereocaulon sp. DMSO extracts was 0.4 mg/ml. E. coli was resistant
      to all kinds of extracts. The S. aureus sensitivity to lichen DMSO extracts was
      comparable to sensitivity of these microorganisms to tetracycline and vancomycin.
      Thereby, most kinds of extracts (ethanol, isopropanol, hexane, DMSO and acetone
      solvents) from Ecuadorian lichens Usnea sp. and Stereocaulon sp. with the
      exception of aqueous Stereocaulon sp. extracts possessed antibacterial activity
      against B. subtilis. DMSO lichen extracts had also antimicrobial activity against
      S. aureus. At the same time the extracts studied didn't demonstrate antibacterial
      activity against the representatives of the most common and harmful
      phytopathogenic bacteria tested. Further investigations of Ecuadorian lichens
      especially study of plants collected from extremal highland biotops can be very
      important in study of possibility of treatment of numerous diseases caused by
      pathogenic microorganisms.

PMID- 26214896
TI  - [BIOCONVERSION OF CRUDE GLYCEROL AND MOLASSES MIXTURE IN BIOSURFACTANTS OF
      NOCARDIA VACCINII IMB B-7405].
AB  - The possibility of replacing glucose and pure glycerol in mixed substrates for
      surtace-active substances (SAS, biosurfactants) biosynthesis of Nocardia vaccinii
      IMB B-7405 on molasses (sugar production waste) and crude glycerol (by-product of
      biodiesel production) was established. It was established that the increasing
      concentration of crude glycerol to 6% in mixture with 1.0% molasses was
      accompanied by increase of amount of SAS synthesized more than twice, and the
      increasing content of molasses to 3.0% in mixture with 1.0% crude glycerol--by
      some decrease in the level of surfactant as compared to that in a medium
      containing 1.0% monosubstrates. It was shown that the increasing concentration of
      sodium nitrate to 2-fold in medium cultivation of N. vaccinii IMB B-7405 allowed
      to increase to 7.0% content of grude glycerol in mixture with 1.0% molasses.
      Under such conditions of cultivation concentration of exocellular SAS synthesized
      was 7,5 g/l, that to 1,3 fold higher than in basic medium with a lower content of
      nitrogen source.

PMID- 26214897
TI  - VIRION MORPHOLOGY AND STRUCTURAL ORGANIZATION OF POLYVALENT BACTERIOPHAGES TT10
      27 AND KEY.
AB  - Fine ultrastructure of polyvalent bacteriophages TT10-27 and KEY isolated from
      affected with fire blight disease plant tissues, was studied using electron
      microscopy. Phages have isometric heads connected to short complex tail (TT10-27,
      C1-morphotype) or long non-contractile tail (KEY B-1 morphotype). Maximum
      diameter of TT10-27 head, measured as the distance between opposite vertices, is
      71.3 nm; tail tube of 22 nm in diameter and 9.0 nm in width is framed with 12
      appendages that form flabellate structure of 47.0-58.6 nm in diameter. KEY
      features capsid of 78.6 nm in diameter and flexible non-contractile tail of 172.5
      nm long, which ends with a conical tip. Due to a number of features phage TT10-27
      was assigned to a group of N4-like phages of Podoviridae family. KEY is a
      representative of family Siphoviridae, the least freaquent group of Erwinia
      amylovora phages.

PMID- 26214898
TI  - [EFFECT OF CALCIUM AND IRON IONS ON THE LEVEL OF DIESEL FUEL UTILIZATION BY
      ACTINOBACTERIA STRAINS].
AB  - It has been established that the presence in the medium Ca2+ and Fe2+ ions in 1.2
      - 1.3 times increases the assimilation of hydrocarbon by actinobacteria. The
      possibility of joint growth of binary actinobacteria cultures on mineral medium
      with diesel fuel without reducing the assimilation of this substrate compared to
      monocultures it was shown. In the conditions of co-batch culture Rhodococcus
      erythropolis IMV B-7277 and Dietzia maris IMV B-7278 strains in the laboratory
      fermenter "Biotec" (stirring speed 500 r.p.m., degree of aeration 0.3 1/1 per
      min, sulfite number 1.5 g O2 /1 h,) on the medium with 1.0% diesel oil in the
      presence of 4 mg/l Ca2+, Fe2+ and 1 g/l yeast extract for 30 hours the substrate
      assimilation rate was 87.8% and the concentration of biomass - 2.0 g/l.

PMID- 26214899
TI  - MULTIPLEX PCR ASSAY FOR DETECTION OF HUMAN SOMATOTROPIN AND INTERFERON ALPHA2b
      GENES IN PLANT MATERIAL.
AB  - Using transgenic plants as factories for production of physiologically active
      human proteins arouses special concern because occasional escape of such
      transgenes into environment may cause health problems. Creation of plant
      varieties producing pharmaceutically valuable proteins should be accompanied by
      development of detection methods suitable for controlling the transgene behavior.
      Here we describe a multiplex PCR protocol for revealing of two human genes
      (encoding growth hormone and interferon alpha2b) that have been successfully
      introduced into plant genomes. The primer pair designed for detection of human
      growth hormone coding sequence amplifies fragments of different size from the
      full-length gene in the human genome and the intronless coding sequence usually
      used for plant transformation. Application of this primer pair may be recommended
      for ruling out false positive results due to sample contamination with human DNA.
      Such a control may be useful also in PCR analysis during establishing of
      transgenic plants carrying genes of human origin.

PMID- 26214900
TI  - [THE ROLE OF STREPTOMYCES NOGALATER Lv65 snoaM, snoaL and snoaE GENES IN
      NOGALAMYCIN BIOSYNTHESIS].
AB  - The results of phylogenetic analysis indicate high similarity of SnoaM, SnoaL
      SnoaE to the cyclases involved in the biosynthesis of various antibiotics. Genes
      snoaM, snoaL and snoaE disruption in S. nogalater chromosome was carried on and
      S. nogalater MI, LI and EI strains were generated. The gene replacement events in
      M1, L1 and E1 were verified by Southern hybridization. Recombinant strains were
      characterised by lack of nogalamycin biosynthesis. Originally, M1, L1 and E1 were
      complemented with plasmids expressing putative cyclase genes from S. nogalater
      leading to restoration of nogalamycine production. The complementation results
      clearly indicate that obtained strains are cyclase deficient mutants.
      Furthermore, complementation of M1, L1 and E1 with a cyclase genes from wild-type
      strain is consistent with the suggested function of these enzymes.

PMID- 26214901
TI  - [MORPHOFUNCTIONAL PARAMETERS OF BLOOD CELLS OF THE RAT WITH 1,2-DIMETHYLHYDRAZINE
      INDUCED COLON CARCINOGENESIS].
AB  - Morphofunctional parameters of blood cells of the rats with dimethylhydrazine
      induced colon carcinogenesis have been investigated. The reduction of Mean
      corpuscular hemoglobin (MCH) and Mean corpuscular hemoglobin concentration (MCHC)
      whereas increasing of reticulocytes number and indirect bilirubin after 20 weeks
      of experiment of dimethylhydrazine (DMH)-induced colon carcinogenesis indicate
      the hemolysis of red blood cells due to the DMH influence during tumors
      development. The moderate increasing of monocytes and platelets number, as well
      as increment of eosinophilic granulocytes number have been observed. 26 weeks of
      experiment (after 6 weeks discontinuation of DMH) leads to reduction of
      hemoglobin and erythrocytes number, a moderate increase of monocytes number and
      increment of platelets number in rats blood. The anemia with thrombocytosis
      accompany cancer in humans and the model of DMH-induced colon cancer is
      appropriate not only for studies of carcinogenesis and searching of new
      antineoplastic drugs, but also for the development of the correctional approaches
      of cancer-associated changes in the hematopoietic system.

PMID- 26214902
TI  - IS THE AMPLIFICATION OF c-MYC, MLL AND RUNX1 GENES IN AML AND MDS PATIENTS WITH
      TRISOMY 8, 11 AND 21 A FACTOR FOR A CLONAL EVOLUTION IN THEIR KARYOTYPE?
AB  - The aim of our study was 1) to define if the amplification of c-MYC, MLL and
      RUNX1 genes is related to the progressive changes of the karyotype in patients
      with AML and MDS with trisomy 8, 11 and 21 (+8, +11 and +21) in bone marrow and
      2) can that amplification be accepted as part of the clonal evolution (CE).
      Karyotype analysis was performed in 179 patients with AML or MDS with the
      different chromosomal aberrations (CA) aged 16-81. The findings were distributed
      as follow: initiating balanced CA (n = 60), aneuploidia (n = 55), unbalanced CA
      (n = 64). Amplification of c-MYC, MLL and RUNX1 genes by means of fluorescence in
      situ hybridization (FISH) was found in 35% (7 out of 20) of AML and MDS patients
      with +8, +11 u +21 as single CA in their karyotype; in 63.6% of pts (7 out of 11)
      -with additional numerical or structural CA and in 75% (9 out of 12)--with
      complex karyotype. We assume that the amplification of the respective chromosomal
      regions in patients with +8, +11 and +21 is related to CE. Considering the
      amplification as a factor of CE, we established 3 patterns of karyotype
      development depending on the type of the initiating CA in it. Significant
      statistical differences were found between the three patterns regarding the
      karyotype distribution in the different stages of progression (p < 0.001).

PMID- 26214903
TI  - [CHROMOSOMAL ABNORMALITIES IN PATIENTS WITH INFERTILITY].
AB  - To assess the frequency and structure of chromosomal abnormalities in patients
      with infertility, a retrospective analysis of cytogenetic studies of 3414
      patients (1741 females and 1673 males), referred to the Clinic of reproductive
      medicine "Nadiya" from 2007 to 2012, was performed. Chromosomal abnormalities
      were detected in 2.37% patients: 2.79% in males and 1.95% in females. Balanced
      structural chromosomal abnormalities prevailed over numerical abnormalities and
      corresponded to 80.2% of all chromosomal abnormalities detected in the studied
      group. Sex chromosome abnormalities made up 23.5% of chromosomal pathology
      (19/81) and included gonosomal aneuploidies in 84% of cases (16/19) and
      structural abnormalities of chromosome Y in 16% of cases (3/19). The low level
      sex chromosome mosaicism was detected with the frequency of 0.55%. Our results
      highlight the importance of cytogenetic studies in patients seeking infertility
      treatment by assisted reproductive technologies, since an abnormal finding not
      only provide a firm diagnosis to couples with infertility, but also influences
      significantly the approach to infertility treatment in such patients.

PMID- 26214904
TI  - [IDENTIFICATION OF MUTATION IVS1-5(G > C) OF THE beta-HEMOGLOBIN GENE (Hbbeta) BY
      RDBH-METHOD IN PATIENTS WITH beta-THALASSEMIA IN AZERBAIJAN].
AB  - The hematological and molecular-genetics analyses of patients with suspected beta
      thalassemia were done by the RDBH StripAssay. The complete blood evaluation (HB,
      MCH, MCV, MCHC, RBC, Hct, HbA2, HbF), monitoring of serum iron and ferritin,
      molecular analysis--RDBH (Reverse Dot-Blot Hybridization StripAssay) were done.
      Two persons were carriers of the beta-thalassemic trait as beta+ thalassemia
      minor IVS1-5(G > > C)/wt. Mutation IVS1-5 (G > C) in the compound with a mutation
      IVS1-110 (G > A) or mutation IVS1-6 (T > C) determines the development of beta
      thalassemia intermedia. RDBH-method is easy and economical method in molecular
      diagnosis of beta-thalassemia, if hematological parameters are incorrect.

PMID- 26214905
TI  - [MICROSATELLITE ANALYSIS OF HOMOEOLOGOUS CHROMOSOME GROUP 5 OF INTROGRESSIVE
      WHEAT LINES TRITICUM AESTIVUM/AMBLYOPYRUM MUTICUM].
AB  - Introgressive hybridization of common wheat is still one of the most effective
      way of wheat genome enrichment with resistance genes to stresses. In this
      context, T genome of Amblyopyrum muticum is a promising one for such wheat
      improvement. Genome substitution amphidiploid Aurotica (AABBTT) with A and B
      subgenomes from common wheat cultivar Aurora and with T subgenome from
      Amblyopyrum muticum is characterized by high level of cold resistance. In wheat,
      this characteristic associated with chromosomes of the homoeologous group 5.
      Comparative microsatellite analysis of Aurora and Aurotica identified 9 SSR loci
      specific to D genome which produced other amplicons with Aurotica DNA spectrum.
      Primers for these loci were used for screening (Aurora x Aurotica)F5 progeny (234
      plants) in purpose to find those individuals, which carry 5T chromosome or its
      fragments in their genomes. In this study were detected 24 plants with disomic
      substitutions 5D/5T. All of them were offspring of five F4 plants, which in turn
      derived from two F2 individuals. A significant number of plants contain
      recombinant chromosome 5D/5T. The recombination event could occur in any
      generation since F2.

PMID- 26214906
TI  - Using optimization methods to align food production and biodiversity conservation
      beyond land sharing and land sparing.
AB  - Aligning food production with biodiversity conservation is one of the greatest
      challenges of our time. One framing of this challenge is the land-sharing vs.
      land-sparing debate. Much empirical research has focused on identifying the
      relationship between agricultural yields and species populations, and using the
      relative number of species with particular relationships to inform landscape
      level management. We feel this is misguided, as such an approach does not
      guarantee the existence of every species of conservation concern. Here, we show
      that constrained optimization methods can be used to identify landscape-level
      solutions which maximize agricultural yields and populations for any number of
      species. Our results suggest that the relative number of species with particular
      yield-density curves is not a good indicator as to how landscapes should be
      managed. Likewise, choosing between blanket sharing or sparing strategies leads
      to suboptimal outcomes at the landscape scale in many cases. Our framework makes
      maximum use of the rich information contained in yield-density curves to move
      beyond black-and-white choices and toward more nuanced, context-specific
      solutions to aligning biodiversity conservation and agricultural production. Such
      optimal landscapes will likely have features of both sharing and sparing
      strategies.

PMID- 26214907
TI  - Phylogenetic signal in amphibian sensitivity to copper sulfate relative to
      experimental temperature.
AB  - The release of large quantities of chemicals into the environment represents a
      major source of environmental disturbance. In recent years, the focus of
      ecotoxicology has shifted from describing the effects of chemical contaminants on
      individual species to developing more integrated approaches for predicting and
      evaluating long term effects of chemicals across species and ecosystems.
      Traditional ecotoxicology is typically based on data of sensitivity to a
      contaminant of a few surrogate species and often considers little variability in
      chemical sensitivity within and among taxonomic groups. This approach assumes
      that evolutionary history and phylogenetic relatedness among species have little
      or no impact on species' sensitivity to chemical compounds. Few studies have
      tested this assumption. Using phylogenetic comparative methods and published data
      for amphibians, we show that sensitivity to copper sulfate, a commonly used
      pesticide, exhibits a strong phylogenetic signal when controlling for
      experimental temperature. Our results indicate that evolutionary history needs to
      be accounted for to make accurate predictions of amphibian sensitivity to this
      contaminant under different temperature scenarios. Since physiological and
      metabolic traits showing high phylogenetic signal likely underlie variation in
      species sensitivity to chemical stressors, future studies should evaluate and
      predict species vulnerability to pollutants using evolutionarily informed
      approaches.

PMID- 26214908
TI  - Temperature is the evil twin: effects of increased temperature and ocean
      acidification on reproduction in a reef fish.
AB  - Reproduction in many organisms can be disrupted by changes to the physical
      environment, such as those predicted to occur during climate change. Marine
      organisms face the dual climate change threats of increasing temperature and
      ocean acidification, yet no studies have examined the potential interactive
      effects of these stressors on reproduction in marine fishes. We used a long-term
      experiment to test the interactive effects of increased temperature and CO2 on
      the reproductive performance of the anemonefish, Amphiprion melanopus. Adult
      breeding pairs were kept for 10 months at three temperatures (28.5 degrees C
      [+0.0 degrees C], 30.0 degrees C [-1.5 degrees C] and 31.5 degrees C [+3.0
      degrees C]) cross-factored with three CO2 levels (a current-day control [417
      uatm] and moderate [644 uatm] and high [1134 uatm]) treatments consistent with
      the range of CO2 projections for the year 2100. We recorded each egg clutch
      produced during the breeding season, the number of eggs laid per clutch, average
      egg size, fertilization success, survival to hatching, hatchling length, and yolk
      provisioning. Adult body condition, hepatosomatic index, gonadosomatic index, and
      plasma 17beta-estradiol concentrations were measured at the end of the breeding
      season to determine the effect of prolonged exposure to increased temperature and
      elevated. CO2 on adults, and to examine potential physiological mechanisms for
      changes in reproduction. Temperature had by far the stronger influence on
      reproduction, with clear declines in reproduction occurring in the +1.5 degrees C
      treatment and ceasing altogether in the +3.0 degrees C treatment. In contrast,
      CO2 had a minimal effect on the majority of reproductive traits measured, but
      caused a decline in offspring quality in combination with elevated temperature.
      We detected no significant effect of temperature or Co2 on adult body condition
      or hepatosomatic index. Elevated temperature had a significant negative effect on
      plasma 17beta-estradiol concentrations, suggesting that declines in reproduction
      with increasing temperature were due to the thermal sensitivity of reproductive
      hormones rather than a reduction in energy available for reproduction. Our
      results show that elevated temperature exerts a stronger influence than high CO2
      on reproduction in A. melanopus. Understanding how these two environmental
      variables interact to affect the reproductive performance of marine organisms
      will be important for predicting the future impacts of climate change.

PMID- 26214909
TI  - Multi-scale model of epidemic fade-out: Will local extirpation events inhibit the
      spread of white-nose syndrome?
AB  - White-nose syndrome (WNS) is an emerging infectious disease that has resulted in
      severe declines of its hibernating bat hosts in North America. The ongoing
      epidemic of white-nose syndrome is a multi-scale phenomenon becau.se it causes
      hibernaculum-level extirpations, while simultaneously spreading over larger
      spatial scales. We investigate a neglected topic in ecological epidemiology: how
      local pathogen-driven extirpations impact large-scale pathogen spread. Previous
      studies have identified risk factors for propagation of WNS over hibernaculum and
      landscape scales but none of these have tested the hypothesis that separation of
      spatial scales and disease-induced mortality at the hibernaculum level might slow
      or halt its spread. To test this hypothesis, we developed a mechanistic multi
      scale model parameterized using white-nose syndrome.county and site incidence
      data that connects hibernaculum-level susceptible-infectious-removed (SIR)
      epidemiology to the county-scale contagion process. Our key result is that
      hibernaculum-level extirpations will not inhibit county-scale spread of WNS. We
      show that over 80% of counties of the contiguous USA are likely to become
      infected before the current epidemic is over and that geometry of habitat
      connectivity is such that host refuges are exceedingly rare. The macroscale
      spatiotemporal infection pattern that emerges from local SIR epidemiological
      processes falls within a narrow spectrum of possible outcomes, suggesting that
      recolonization, rescue effects, and multi-host complexities at local scales are
      not important to forward propagation of WNS at large spatial scales. If effective
      control measures are not implemented, precipitous declines in bat populations are
      likely, particularly in cave-dense regions that constitute the main geographic
      corridors of the USA, a serious concern for bat conservation.

PMID- 26214910
TI  - Polar bear population dynamics in the southern Beaufort Sea during a period of
      sea ice decline.
AB  - In the southern Beaufort Sea of the United States and Canada, prior
      investigations have linked declines in summer sea ice to reduced physical
      condition, growth, and survival of polar bears (Ursus maritimus). Combined with
      projections of population decline due to continued climate warming and the
      ensuing loss of sea ice habitat, those findings contributed to the 2008 decision
      to list the species as threatened under the U.S. Endangered Species Act. Here, we
      used mark-recapture models to investigate the population dynamics of polar bears
      in the southern Beaufort Sea from 2001 to 2010, years during which the spatial
      and temporal extent of summer sea ice generally declined. Low survival from 2004
      through 2006 led to a 25-50% decline in abundance. We hypothesize that low
      survival during this period resulted from (1) unfavorable ice conditions that
      limited access to prey during multiple seasons; and possibly, (2) low prey
      abundance. For reasons that are not clear, survival of adults and cubs began to
      improve in 2007 and abundance was comparatively stable from 2008 to 2010, with
      ~900 bears in 2010 (90% CI 606-1212). However, survival of subadult bears
      declined throughout the entire period. Reduced spatial and temporal availability
      of sea ice is expected to increasingly force population dynamics of polar bears
      as the climate continues to warm. However, in the short term, our findings
      suggest that factors other than sea ice can influence survival. A refined
      understanding of the ecological mechanisms underlying polar bear population
      dynamics is necessary to improve projections of their future status and
      facilitate development of management strategies.

PMID- 26214911
TI  - Trophic cascades in agricultural landscapes: indirect effects of landscape
      composition on crop yield.
AB  - The strength and prevalence of trophic cascades, defined as positive, indirect
      effects of natural enemies (predatory and parasitic arthropods) on plants, is
      highly variable in agroecosystems. This variation may in part be due to the
      spatial or landscape context in which hese trophic cascades occur. In 2011 and
      2012, we conducted a natural enemy exclusion experiment in soybean fields along a
      gradient of landscape composition across southern Wisconsin and Michigan, USA. We
      used structural equation modeling to ask (1) whether natural enemies influence
      biocontrol of soybean aphids (SBA) and soybean yield and (2) whether landscape
      effects on natural enemies influence the strength of the trophic cascades. We
      found that natural enemies (NE) suppressed aphid populations in both years of our
      study, and, in 2011, the yield of soybean plants exposed to natural enemies was
      37% higher than the yield of plants with aphid populations protected from natural
      enemies. The strength of the :rophic cascade was also influenced by landscape
      context. We found that landscapes with a higher proportion of soybean and higher
      diversity habitats resulted in more NE, fewer aphids, and, in some cases, a trend
      toward greater soybean yield. These results indicate that landscape context is
      important for understanding spatial variability in biocontrol and yield, but
      other factors, such as environmental variability and compensatory growth, might
      overwhelm the beneficial effects of biocontrol on crop yield.

PMID- 26214912
TI  - Spatial heterogeneity increases diversity and stability in grassland bird
      communities.
AB  - Grasslands are inherently dynamic in space and time, evolving with frequent
      disturbance from fire and herbivores. As a consequence of human actions, many
      remaining grasslands have become homogenous, which has led to reduced ecosystem
      function, biodiversity loss, and decreased ecological services. Previous research
      has shown that restoring inherent heterogeneity to grasslands can increase avian
      diversity, but the amount of heterogeneity (i.e., number of patches or fire
      return interval) and the impact on avian community stability have yet to be
      investigated. We used a unique landscape-level design to examine avian response
      to interacting fire and grazing across multiple experimental landscapes that
      represented a gradient of fire- and grazing-dependent heterogeneity. We used
      seven landscapes (430-980 ha; x = 627 ha) with varying levels of patchiness
      ranging from annually burned (one single patch) with spring-only fires to a four
      year fire return interval with spring and summer fires (eight patches). This
      design created a range of heterogeneity as a result of pyric herbivory, an
      ecological process in which fire and grazing are allowed to interact in space and
      time. We found that greater heterogeneity across experimental landscapes resulted
      in increased avian diversity and stability over time. An index of bird community
      change, quantified as the sum of the range of detrended correspondence analysis
      axis site scores, was nearly four times greater in the most homogenous
      experimental landscape when compared to the most heterogeneous experimental
      landscape. Species responses were consistently positively associated with
      increased heterogeneity at the landscape scale, and within-experimental-landscape
      responses were most often related to litter cover, litter accumulation, and
      vegetation height. We conclude that increased fire- and grazig-dependent
      heterogeneity can result in high variability in the bird community at finer,
      transect scales, but increased diversity and stability at broad landscape scales.
      We recommend that future management efforts in rangelands focus on restored
      disturbance processes to increase heterogeneity and improve grassland bird
      conservation.

PMID- 26214913
TI  - Patterns in diurnal airspace use by migratory landbirds along an ecological
      barrier.
AB  - Migratory bird populations and survival are affected by conditions experienced
      during migration. While many studies and conservation and management efforts
      focus on terrestrial stoppage and staging areas, the aerial environment through
      which migrants move also is subjected to anthropogenic impacts with potential
      consequences to migratory movement and survival. During autumn migration, the
      northern coastline of Lake Superior acts as an ecological barrier for many
      landbirds migrating out of the boreal forests of North America. From 24
      observation points, we assessed the diurnal movements of birds throughout autumn
      migration, 2008-2010, within a 210 * 10 km coastal region along the northern
      coast of Lake Superior. Several raptor species showed patterns in airspace
      associated with topographic features such as proximity to the coastline and
      presence of ridgelines. Funneling movement, commonly used to describe the
      concentration of raptors along a migratory diversion line that either prevents or
      enhances migration progress, occurred only for Bald and Golden Eagles. This
      suggests a "leaky" migration funnel for most migratory raptors (e.g., migrating
      birds exiting the purported migration corridor). Passerines migrating during the
      late season showed more spatial and temporal structure in airspace distribution
      than raptors did, including funneling and an association with airspace near the
      coast. We conclude that (1) the diurnal use of airspace by many migratory
      landbirds is patterned in space and time, (2) autumn count sites situated along
      ecological barriers substantially underestimate the number of raptors due to
      "leakage" out of these concentration areas, and (3) the magnitude and structure
      of diurnal passerine movements in airspace have been overlooked. The heavy and
      structured use of airspace by migratory landbirds, especially the airspace
      associated with anthropogenic development (e.g., buildings, towers, turbines)
      necessitates a shift in focus to airspace management and conservation attention
      for these animals.

PMID- 26214914
TI  - Community occupancy before-after-control-impact (CO-BACI) analysis of Hurricane
      Gudrun on Swedish forest birds.
AB  - Resilience of ecological communities to perturbation is important in the face of
      increased global change from anthropogenic stressors. Monitoring is required to
      detect the impact of, and recovery from, perturbations, and before-after-control
      impact (BACI) analysis provides a powerful framework in this regard. However,
      species in a community are not observed with perfect detection, and occupancy
      analysis is required to correct for imperfect detectability of species. We
      present a Bayesian community occupancy before-after-control-impact (CO-BACI)
      framework to monitor ecological community response to perturbation when
      constituent species are imperfectly detected. We test the power of the model to
      detect changes in community composition following an acute perturbation with
      simulation. We then apply the model to a study of the impact of a large hurricane
      on the forest bird community of Sweden, using data from the national bird survey
      scheme. Although simulation shows the model can detect changes in community
      occupancy following an acute perturbation, application to a Swedish forest bird
      community following a major hurricane detected no change in community occupancy
      despite widespread forest loss. Birds with landscape occupancy less than 50%
      required correcting for detectability. We conclude that CO-BACI analysis is a
      useful tool that can incorporate rare species in analyses and detect occupancy
      changes in ecological communities following perturbation, but, because it does
      not include abundance, some impacts may be overlooked.

PMID- 26214915
TI  - Spatial capture-recapture model performance with known small-mammal densities.
AB  - Abundance and density of wild animals are important ecological metrics. However,
      estimating either is fraught with challenges; spatial capture-recapture (SCR)
      models are a relatively new class of models that attempt to ameliorate common
      challenges, providing a statistically coherent framework to estimate abundance
      and density. SCR models are increasingly being used in ecological and
      conservation studies of mammals worldwide, but have received little testing with
      empirical field data. We use data collected via a web and grid sampling design to
      evaluate the basic SCR model where small-mammal abundance (N) and density (D) are
      known (via exhaustive sampling). We fit the basic SCR model with and without a
      behavioral effect to 11 small-mammal populations for each sampling design using a
      Bayesian and likelihood SCR modeling approach. We compare SCR and ad hoc density
      estimators using frequentist performance measures. We found Bayesian and
      likelihood SCR estimates of density (D) and abundance (N) to be similar. We also
      found SCR models to have moderately poor frequentist coverage of D and N (45
      73%), high deviation from truth (i.e., accuracy; D, 17-29%; N, 16-29%), and
      consistent negative bias across inferential paradigms, sampling designs, and
      models. With the trapping grid data, the basic SCR model generally performed more
      poorly than the best ad hoc estimator (behavior CR super-population estimate
      divided by the full mean maximum distance moved estimate of the effective
      trapping area), whereas with the trapping web data, the best-performing SCR model
      (null) was comparable to the best distance model. Relatively poor frequentist SCR
      coverage resulted from higher precision (SCR coefficients of variation [CVs] < ad
      hoc CVs); however D and D were fairly well correlated (r2 range of 0.77-0.96).
      SCR's negative relative bias (i.e., average underestimation of the true density)
      suggests additional heterogeneity in detection and/or that small mammals
      maintained asymmetric home ranges. We suggest caution in the use of the basic SCR
      model when trapping animals in a sampling grid and more generally when small
      sample sizes necessitate the spatial scale parameter (sigma) apply to all
      individuals. When possible, researchers should consider variation in detection
      and incorporate individual biological and/or ecological variation at the trap
      level when modeling sigma.

PMID- 26214916
TI  - Ecological impacts of invasive alien species along temperature gradients: testing
      the role of environmental matching.
AB  - Invasive alien species (IAS) can cause substantive ecological impacts, and the
      role of temperature in mediating these impacts may become increasingly
      significant in a changing climate. Habitat conditions and physiological optima
      offer predictive information for IAS impacts in novel environments. Here, using
      meta-analysis and laboratory experiments, we tested the hypothesis that the
      impacts of IAS in the field are inversely correlated with the difference in their
      ambient and optimal temperatures. A meta-analysis of 29 studies of consumptive
      impacts of IAS in inland waters revealed that the impacts of fishes and
      crustaceans are higher at temperatures that more closely match their thermal
      growth optima. In particular, the maximum impact potential was constrained by
      increased differences between ambient and optimal temperatures, as indicated by
      the steeper slope of a quantile regression on the upper 25th percentile of impact
      data compared to that of a weighted linear regression on all data with measured
      variances. We complemented this study with an experimental analysis of the
      functional response (the relationship between predation rate and prey supply) of
      two invasive predators (freshwater mysid shrimp, Hemimysis anomala and Mysis
      diluviana) across. relevant temperature gradients; both of these species have
      previously been found to exert strong community-level impacts that are
      corroborated by their functional responses to different prey items. The
      functional response experiments showed that maximum feeding rates of H. anomala
      and M. diluviana have distinct peaks near their respective thermal optima.
      Although variation in impacts may be caused by numerous abiotic or biotic habitat
      characteristics, both our analyses point to temperature as a key mediator of IAS
      impact levels in inland waters and suggest that IAS management should prioritize
      habitats in the invaded range that more closely match the thermal optima of
      targeted invaders.

PMID- 26214917
TI  - Rating impacts in a multi-stressor world: a quantitative assessment of 50
      stressors affecting the Great Lakes.
AB  - Ecosystems often experience multiple environmental stressors simultaneously that
      can differ widely in their pathways and strengths of impact. Differences in the
      relative impact of environmental stressors can guide restoration and management
      prioritization, but few studies have empirically assessed a comprehensive suite
      of stressors acting on a given ecosystem. To fill this gap in the Laurentian
      Great Lakes, where considerable restoration investments are currently underway,
      we used expert elicitation via a detailed online survey to develop ratings of the
      relative impacts of 50 potential stressors. Highlighting the multiplicity of
      stressors in this system, experts assessed all 50 stressors as having some impact
      on ecosystem condition, but ratings differed greatly among stressors. Individual
      stressors related to invasive and nuisance species (e.g., dreissenid mussels and
      ballast invasion risk) and climate change were assessed as having the greatest
      potential impacts. These results mark a shift away from the longstanding emphasis
      on nonpoint phosphorus and persistent bioaccumulative toxic substances in the
      Great Lakes. Differences in impact ratings among lakes and ecosystem zones were
      weak, and experts exhibited surprisingly high levels of agreement on the relative
      impacts of most stressors. Our results provide a basin-wide, quantitative summary
      of expert opinion on the present-day influence of all major Great Lakes
      stressors. The resulting ratings can facilitate prioritizing stressors to achieve
      management objectives in a given location, as well as providing a baseline for
      future stressor impact assessments in the Great Lakes and elsewhere.

PMID- 26214918
TI  - Managing the wildlife tourism commons.
AB  - The nonlethal effects of wildlife tourism can threaten the conservation status of
      targeted animal populations. In turn, such resource depletion can compromise the
      economic viability of the industry. Therefore, wildlife tourism exploits
      resources that can become common pool and that should be managed accordingly. We
      used a simulation approach to test whether different management regimes (tax, tax
      and subsidy, cap, cap and trade) could provide socioecologically sustainable
      solutions. Such schemes are sensitive to errors in estimated management targets.
      We determined the sensitivity of each scenario to various realistic uncertainties
      in management implementation and in our knowledge of the population. Scenarios
      where time quotas were enforced using a tax and subsidy approach, or they were
      traded between operators were more likely to be sustainable. Importantly,
      sustainability could be achieved even when operators were assumed to make simple
      rational economic decisions. We suggest that a combination of the two regimes
      might offer a robust solution, especially on a small spatial scale and under the
      control of a self-organized, operator-level institution. Our simulation platform
      could be parameterized to mimic local conditions and provide a test bed for
      experimenting different governance solutions in specific case studies.

PMID- 26214919
TI  - Profiling crop pollinators: life history traits predict habitat use and crop
      visitation by Mediterranean wild bees.
AB  - Wild pollinators, bees in particular, may greatly contribute to crop pollination
      and provide a safety net against declines in commercial pollinators. However, the
      identity, life history traits, and environmental sensitivities of main crop
      pollinator species.have received limited attention. These are crucial for
      predicting pollination services of different communities and for developing
      management practices that enhance crop pollinators. We sampled wild bees in three
      crop systems (almond, confection sunflower, and seed watermelon) in a mosaic
      Israeli Mediterranean landscape. Bees were sampled in field/orchard edges and
      interiors, and in seminatural scrub surrounding the fields/orchards. We also
      analyzed land cover at 50-2500 m radii around fields/orchards. We used this data
      to distinguish crop from non-crop pollinators based on a set of life history
      traits (nesting, lecty, sociality, body size) linked to habitat preference and
      crop visitation. Bee abundance and species richness decreased from the
      surrounding seminatural habitat to the field/orchard interior, especially across
      the seminatural habitat-field edge ecotone. Thus, although rich bee communities
      were found near fields, only small fractions crossed the ecotone and visited crop
      flowers in substantial numbers. The bee assemblage in agricultural
      fields/orchards and on crop flowers was dominated by ground-nesting bees of the
      tribe Halictini, which tend to nest within fields. Bees' habitat preferences were
      determined mainly by nesting guild, whereas crop visitation was determined mainly
      by sociality. Lecty and body size also affected both measures. The percentage of
      surrounding seminatural habitat at 250-2500 m radii had a positive effect on wild
      bee diversity in field edges, for all bee guilds, while at 50-100 m radii, only
      aboveground nesters were positively affected. In sum, we found that crop and non
      crop pollinators are distinguished by behavioral and morphological traits. Hence,
      analysis of life-history traits of bee communities can help assess the
      pollination services they are likely to provide (when taking into account single
      visit pollination efficiency). The ecotone between agricultural fields and
      surrounding habitats is a major barrier that filters many bee species,
      particularly with regard to their nesting requirements. Thus, greater attention
      should be given to management practices that encourage pollinators to live and
      nest, and not only forage, within fields.

PMID- 26214920
TI  - Connecting differential responses of native and invasive riparian plants to
      climate change and environmental alteration.
AB  - Climate change is predicted to impact river systems in the southeastern United
      States through alterations of temperature, patterns of precipitation and
      hydrology. Future climate scenarios for the southeastern United States predict
      (1) surface water temperatures will warm in concert with air temperature, (2)
      storm flows will increase and base flows will decrease, and (3) the annual
      pattern of synchronization between hydroperiod and water temperature will be
      altered. These alterations are expected to disturb floodplain plant communities,
      making them more vulnerable to establishment of invasive species. The primary
      objective of this study is to evaluate whether native and invasive riparian plant
      assemblages respond differently to alterations of climate and land use. To study
      the response of riparian wetlands to watershed and climate alterations, we
      utilized an existing natural experiment imbedded in gradients of temperature and
      hydrology-found among dammed and undammed rivers. We evaluated a suite of
      environmental variables related to water temperature, hydrology, watershed
      disturbance, and edaphic conditions to identify the strongest predictors of
      native and invasive species abundances. We found that native species abundance is
      strongly influenced by climate-driven variables such as temperature and
      hydrology, while invasive species abundance is more strongly influenced by site
      specific factors such as land use and soil nutrient availability. The patterns of
      synchronization between plant phenology, annual hydrographs, and annual water
      temperature cycles may be key factors sustaining the viability of native riparian
      plant communities. Our results demonstrate the need to understand the
      interactions between climate, land use, and nutrient management in maintaining
      the species diversity of riparian plant communities. Future climate change is
      likely to result in diminished competitiveness of native plant species, while the
      competitiveness of invasive species will increase due to anthropogenic watershed
      disturbance and accelerated nutrient and sediment export.

PMID- 26214921
TI  - Bumble bee nest abundance, foraging distance, and host-plant reproduction:
      implications for management and conservation.
AB  - Recent reports of global declines in pollinator species imply an urgent need to
      assess the abundance of native pollinators and density-dependent benefits for
      linked plants. In this study, we investigated (1) pollinator nest distributions
      and estimated colony abundances, (2) the relationship between abundances of
      foraging workers and the number of nests they represent, (3) pollinator foraging
      ranges, and (4) the relationship between pollinator abundance and plant
      reproduction. We examined these questions in an alpine ecosystem in the Colorado
      Rocky Mountains, focusing on four alpine bumble bee species (Bombus balteatus, B.
      flavifrons, B. bifarius, and B. sylvicola), and two host plants that differ in
      their degrees of pollinator specialization (Trifolium dasyphyllum and T. parryi).
      Using microsatellites, we found that estimated colony abundances among Bombus
      species ranged from ~18 to 78 colonies/0.01 km2. The long-tongued species B.
      balteatus was most common, especially high above treeline, but the subalpine
      species B. bifarius was unexpectedly abundant for this elevation range. Nests
      detected among sampled foragers of each species were correlated with the number
      of foragers caught. Foraging ranges were smaller than expected for all Bombus
      species, ranging from 25 to 110 m. Fruit set for the specialized plant, Trifolium
      parryi, was positively related to the abundance of its Bombus pollinator. In
      contrast, fruit set for the generalized plant, T. dasyphyllum, was related to
      abundance of all Bombus species. Because forager abundance was related to nest
      abundance of each Bombus species and was an equally effective predictor of plant
      fecundity, forager inventories are probably suitable for assessing the health of
      outcrossing plant populations. However, nest abundance, rather than forager
      abundance, better reflects demographic and genetic health in populations of
      eusocial pollinators such as bumble bees. Development of models incorporating the
      parameters we have measured here (nest abundance, forager abundance, and foraging
      distance) could increase the usefulness of foraging worker inventories in
      nionitoring, managing, and conserving pollinator populations.

PMID- 26214922
TI  - NDVI as a predictor of canopy arthropod biomass in the Alaskan arctic tundra.
AB  - The physical and biological responses to rapid arctic warming are proving acute,
      and as such, there is a need to monitor, understand, and predict ecological
      responses over large spatial and temporal scales. The use of the normalized
      difference vegetation index (NDVI) acquired from airborne and satellite sensors
      addresses this need, as it is widely used as a tool for detecting and quantifying
      spatial and temporal dynamics of tundra vegetation cover, productivity, and
      phenology. Such extensive use of the NDVI to quantify vegetation characteristics
      suggests that it may be similarly applied to characterizing primary and secondary
      consumer communities. Here, we develop empirical models to predict canopy
      arthropod biomass with canopy-level measurements of the NDVI both across and
      within distinct tundra vegetation communities over four growing seasons in the
      Arctic Foothills region of the Brooks Range, Alaska, USA. When canopy arthropod
      biomass is predicted with the NDVI across all four growing seasons, our overall
      model that includes all four vegetation communities explains 63% of the variance
      in canopy arthropod biomass, whereas our models specific to each of the four
      vegetation communities explain 74% (moist tussock tundra), 82% (erect shrub
      tundra), 84% (riparian shrub tundra), and 87% (dwarf shrub tundra) of the
      observed variation in canopy arthropod biomass. Our field-based study suggests
      that measurements of the NDVI made from air- and spaceborne sensors may be able
      to quantify spatial and temporal variation in canopy arthropod biomass at
      landscape to regional scales.

PMID- 26214923
TI  - Short-term priority over exotic annuals increases the initial density and longer
      term cover of native perennial grasses.
AB  - Temporal priority can affect individual performance and reproduction, as well as
      community assembly, but whether these effects persist over time remains unclear,
      and their demographic mechanisms have been little explored. The continued
      dominance of exotic annual grasses in California has been commonly attributed to
      their demonstrated early germination and rapid early growth relative to native
      perennial grasses. This advantage may play a crucial role in the structure of
      California exotic annual grasslands, as well as in the practice of native
      grassland restoration. We tested whether a two-week planting advantage under
      field conditions increased individual survival, growth, and reproduction for four
      native perennial grass species and whether these effects persisted over three
      years. We show that short-term priority significantly increased the establishment
      success of' native perennial grasses. Increased density of native grass seedlings
      presaged later large increases in cover that were not evident in the first year
      after planting. Although priority effects at the individual level may diminish
      over time, short differences in emergence timing can have long-lasting effects on
      community structure. Earlier germination and faster initial growth of exotic
      annual species may help explain their unprecedented invasion and continued
      dominance of California grasslands. Finally, these results highlight the
      importance of priority effects for effective exotic annual control during native
      grassland restoration in California: initial control can increase the
      establishment of native perennial seedlings, which then results in long-term
      control by mature native individuals.

PMID- 26214924
TI  - Living near the edge: Being close to mature forest increases the rate of
      succession in beetle communities.
AB  - In increasingly fragmented landscapes, it is important to understand how mature
      forest affects adjacent secondary forest (forest influence). Forest influence on
      ecological succession of beetle communities is largely unknown. We investigated
      succession and forest influence using 235 m long transects across boundaries
      between mature and secondary forest at 15 sites, sampling a chronosequence of
      three forest age classes (5-10, 23- 29, and 42-46 years since clear-cutting) in
      tall eucalypt forest in Tasmania, Australia. Our results showed that ground
      dwelling beetle communities showed strong successional changes, and in the oldest
      secondary forests, species considered indicators of mature forest had recolonized
      to abundance levels similar to those observed within adjacent mature forest
      stands. However, species composition also showed forest influence gradients in
      all age classes. Forest influence was estimated to extend 13 m and 20 m in the
      youngest and intermediate-aged secondary forests, respectively. However, the
      estimated effect extended to at least 176 m in the oldest secondary forest. Our
      environmental modeling suggests that leaf litter, microclimate, and soil
      variables were all important in explaining the spatial variation in beetle
      assemblages, and the relative importance of factors varied between secondary
      forest age classes. Mature-forest beetle communities can recolonize successfully
      from the edge, and our results provide a basis for land managers to build mature
      habitat connectivity into forest mosaics typical of production forests. Our
      results also indicate the importance of forest influence in determining potential
      conservation value of older secondary forest for beetles.

PMID- 26214925
TI  - Relative effects of landscape-scale wetland amount and landscape matrix quality
      on wetland vertebrates: a 'meta-analysis.
AB  - Conservation management of wetland-dependent species generally focuses on
      preserving or increasing wetland habitat. However, the quality of the landscape
      matrix (the intervening non-wetland portion of the landscape) has been shown to
      be more important than wetland availability for some wetland-dependent species.
      We used meta-analysis to compare the effects of wetland amount (measured as the
      area of wetland habitat in a landscape) and matrix quality (measured as the area
      of forest cover in the same landscape) on the population abundance of wetland
      dependent vertebrates. We combined data across 63 studies conducted in forested
      ecoregions worldwide and extracted 330 population responses for 155 species, at
      the spatial scale that best predicted the effects of wetland. amount and forest
      amount for each response. In addition, to ensure that our results were not biased
      by the scale selected, we assessed whether the relative effects of wetland and
      forest amount were scale dependent. We found that the amount of wetland in a
      landscape had a larger effect than the amount of forest on the abundance of
      mammals and birds whereas, surprisingly, for amphibians the amount of forest in a
      landscape was more important than the amount of wetland. For reptiles, both
      wetland amount and forest amount showed only weak,effects on abundance. These
      results were not scale dependent, i.e., they were consistent across spatial
      scales. Our results suggest that the population distribution of wetland-dependent
      amphibians is more strongly related to landscape matrix quality than to wetland
      availability in a landscape, likely due to their requirement for access to
      terrestrial resources. We conclude that conservation policies for wetland
      biodiversity that focus only on wetland habitat will be ineffective in conserving
      many of these species. In addition, population viability analyses based only on
      wetland amount may overestimate the capacity of a landscape to support
      populations of wetland-dependent species.

PMID- 26214926
TI  - From forager tracks to prey distributions: an application to tuna vessel
      monitoring systems (VMS).
AB  - In the open ocean, movements of migratory fish populations are typically surveyed
      using tagging methods that are subject to low sample sizes for archive tags,
      except for a few notable examples, and poor temporal resolution for conventional
      tags. Alternatively, one can infer patterns of movement of migratory fish by
      tracking movements of their predators, i.e., fishing vessels, whose navigational
      systems (e.g., GPS) provide accurate and frequent VMS (vessel monitoring system)
      records of movement in pursuit of prey. In this paper, we develop a state-space
      model that infers the foraging activities of fishing vessels from their tracks.
      Second, we link foraging activities to probabilities of tuna presence. Finally,
      using multivariate geostatistical interpolation (cokriging) we map the
      probability of tuna presence together with their estimation variances and produce
      a time series of indices of abundance. While the segmentation of the trajectories
      is validated by observers' data, the present VMS-index is compared to catch rate
      and proved to be useful for management perspectives. The approach reported in
      this manuscript extends beyond the case study considered. It can be applied to
      any foragers that engage in an attempt of capture when they see prey and for whom
      this attempt is linked to a tractable change in behavior.

PMID- 26214927
TI  - Quantifying canopy complexity and effects on productivity and resilience in late
      successional hemlock-hardwood forests.
AB  - The regrowing forests of eastern North America have been an important global C
      sink over the past 100+ years, but many are now transitioning into late
      succession. The consequences of this transition are unclear due to uncertainty
      around the C dynamics of old- growth forests. Canopy structural complexity (CSC)
      has been shown to be an important source of variability in C dynamics in younger
      forests (e.g., in productivity and resilience to disturbance), but its role in
      late-successional forests has not been widely addressed. We investigated patterns
      of CSC in two old-growth forest landscapes in the Upper Peninsula of Michigan,
      USA, to assess factors associated with CSC and its influence on productivity and
      disturbance resilience (to moderate-severity windstorm). CSC was quantified using
      a portable below-canopy LiDAR (PCL) system in 65 plots that also had long-term
      (50-70+ years). inventory data, which were used to quantify aboveground net
      primary productivity (ANPP), disturbance history, and stand characteristics. We
      found high and variable CSC relative to younger forests across a suite of PCL
      derived metrics. Variation in CSC was driven by species composition and size
      structure, rather than disturbance history or site characteristics. Recent
      moderate severity wind disturbance decreased plot-scale CSC, but increased stand
      scale variation in CSC. The strong positive correlation between CSC and
      productivity illustrated in younger forests was not present in undisturbed
      portions of these late-successional ecosystems. Moderate severity disturbance
      appeared to reestablish the positive link between CSC and productivity, but this
      relationship was scale and severity dependent. A positive CSC-productivity
      relationship was evident at the plot scale with low-severity, dispersed
      disturbance, but only at a patch scale in more severely disturbed areas. CSC does
      not appear to strongly correlate With variation in productivity in undisturbed
      old-growth forests, but may play a very important (and scale/severity-dependent)
      role in their response to disturbance. Understanding potential, drivers and
      consequences of CSC in late-successional forests will inform management focused
      on promoting complexity and old-growth conditions, and illustrate potential
      inipacts of such treatments on regional C dynamics.

PMID- 26214928
TI  - Species-abundance--seed-size patterns within a plant community affected by
      grazing disturbance.
AB  - Seed size has been advanced as a key factor that influences the dynamics of plant
      communities, but there are few empirical or theoretical predictions of how
      community dynamics progress based on seed size patterns. Information on the
      abundance of adults, seedlings, soil seed banks, seed rains, and the seed mass of
      96 species was collected in alpine meadows of the Qinghai-Tibetan Plateau
      (China), which had different levels of grazing disturbance. The relationships
      between seed-mass-abundance patterns for adults, seedlings, the soil seed bank,
      and seed rain in the plant community were evaluated using regression models.
      Results showed that grazing levels affected the relationship between seed size
      and abundance properties of adult species, seedlings, and the soil seed bank,
      suggesting that there is a shift in seed-size--species-abundance relationships as
      a response to the grazing gradient. Grazing had no effect on the pattern of seed
      size-seed-rain-abundance at four grazing levels. Grazing also had little effect
      on the pattern of seed-size--species-abundance and pattern of seed-size--soil
      seed-bank-abundance in meadows with no grazing, light grazing, and moderate
      grazing), but there was a significant negative effect in meadows with heavy
      grazing. Grazing had little effect on the pattern of seed-size--seedling
      abundance with no grazing, but had significant negative effects with light,
      moderate, and heavy grazing, and the |r| values increased with grazing levels.
      This indicated that increasing grazing pressure enhanced the advantage of smaller
      seeded species in terms of the abundances of adult species, seedlings, and soil
      seed banks, whereas only the light grazing level promoted the seed rain abundance
      of larger-seeded species in the plant communities. This study suggests that
      grazing disturbances are favorable for increasing the species abundance for
      smaller-seeded species but not for the larger-seeded species in an alpine meadow
      community. Hence, there is a clear advantage of the smaller-seeded species over
      the larger-seeded species with increases in the grazing level.

PMID- 26214929
TI  - Low-to-moderate nitrogen and phosphorus concentrations accelerate microbially
      driven litter breakdown rates.
AB  - Particulate organic matter (POM) processing is an important driver of aquatic
      ecosystem productivity that is sensitive to nutrient enrichment and.drives
      ecosystem carbon (C) loss. Although studies of single concentrations of nitrogen
      (N) or phosphorus (P) have shown effects at relatively low concentrations,
      responses of litter breakdown rates along gradients of low-to-moderate N and P
      concentrations are needed to establish likely interdependent effects of dual N
      and P enrichment on baseline activity in stream ecosystems. We established 25
      combinations of dissolved inorganic N (DIN; 55-545 ug/L) and soluble reactive P
      (SRP; 4-86 ug/L) concentrations with corresponding N:P molar ratios of 2-127 in
      experimental stream channels. We excluded macroinvertebrates, focusing on
      microbially driven breakdown of maple (Acer rubrum L.) and rhododendron
      (Rhododendron maximum L.) leaf litter. Breakdown rates, k, per day (d-1) and per
      degree-day (dd-l), increased by up to 6X for maple and 12* for rhododendron over
      our N and P enrichment gradient compared to rates at low ambient N and P
      concentrations. The best models of k (d- and dd-1) included litter species
      identity and N and P concentrations; there was evidence for both additive and
      interactive effects of N and P. Models explaining variation in k dd-1 were
      supported by N and P for both maple and rhododendron (R =0.67 and 0.33,
      respectively). Residuals in the relationship between k dd-1 and N concentration
      were largely explained by P, but residuals for k dd-1 and P. concentration were
      less adequately explained by N. Breakdown rates were more closely related to
      nutrient concentrations than variables associated with measurements of two
      mechanistic parameters associated with C loss (fungal biomass and microbial
      respiration rate). We also determined the effects of nutrient addition on litter
      C: nutrient stoichiometry and found reductions in litter C:N and C:P along our
      experimental nutrient gradient. Our results indicate that microbially driven
      litter processing rates increase across low-to-moderate nutrient gradients that
      are now common throughout human-modified landscapes.

PMID- 26214930
TI  - Do microorganism stoichiometric alterations affect carbon sequestration in paddy
      soil subjected to phosphorus input?
AB  - Ecological stoichiometry provides a powerful tool for integrating microbial
      biomass stoichiometry with ecosystem processes, opening far-reaching
      possibilities for linking microbial dynamics to soil carbon (C) metabolism in
      response to agricultural nutrient management. Despite its importance to crop
      yield, the role of phosphorus (P) with respect to ecological stoichiometry and
      soil C sequestration in paddy fields remains poorly understood, which limits our
      ability to predict nutrient-related soil C cycling. Here, we collected soil
      samples from a paddy field experiment after seven years of superphosphate
      application along a gradient of 0, 30, 60, and 90 (P-0 through P-90,
      respectively) kg.ha-1.yr-1 in order to evaluate the role of exogenous P on soil C
      sequestration through regulating microbial stoichiometry. P fertilization
      increased soil total organic C and labile organic C by 1-14% and 4-96%,
      respectively, while rice yield is a function of the activities of soil beta-1,4
      glucosidase (BG), acid phosphatase (AP), and the level of available soil P
      through a stepwise linear regression model. P input induced C limitation, as
      reflected by decreases in the ratios of C:P in soil and microbial biomass. An eco
      enzymatic ratio indicating microbial investment in C vs. P acquisition, i.e.,
      ln(BG): ln(AP), changed the ecological function of microbial C acquisition, and
      was stoichiometrically related to P input. This mechanism drove a shift in soil
      resource availability by increasing bacterial community richness and diversity,
      and stimulated soil C sequestration in the paddy field by enhancing C-degradation
      related bacteria for the breakdown of plant-derived carbon sources. Therefore,
      the decline in the C:P stoichiometric ratio of soil microorganism biomass under P
      input was beneficial for soil C sequestration, which offered a "win-win"
      relationship for the maximum balance point between C sequestration and P
      availability for rice production in the face of climate change.

PMID- 26214931
TI  - Nurse Staffing: The Knowns and Unknowns.

PMID- 26214932
TI  - Do Associate Degree Registered Nurses Fare Differently in the Nurse Labor Market
      Compared to Baccalaureate-Prepared RNs?
AB  - Roughly 40% of the nearly 3 million registered nurses (RNs) in the United States
      have an associate's degree (ADN) as their highest level of nursing education. Yet
      even before the recent Institute of Medicine report on The Future of Nursing,
      employers of RNs have increasingly preferred baccalaureate-prepared RNs (BSNs),
      at least anecdotally. Data from the American Community Survey (2003-2013) were
      analyzed with respect to employment setting, earnings, and employment outcomes of
      ADN and BSN-prepared RNs. The data reveal a divergence in employment setting: the
      percentage of ADN-prepared RNs employed in hospitals dropped from 65% to 60%
      while the percentage of BSN-prepared RNs employed in hospitals grew from 67% to
      72% over this period. Many ADNs who would have otherwise been employed in
      hospitals seem to have shifted to long-term care settings.

PMID- 26214933
TI  - Nursing Care Value-Based Financial Models.
AB  - Nursing care makes up one of the largest expenditures in the health care system,
      yet patient-level nursing intensity and costs are essentially unknown. Prior
      efforts to define nursing care value have been stymied by a lack of available
      data; however, emerging information from electronic health records provide an
      opportunity to measure nursing care in ways that have not been possible. New
      metrics using these data will allow improved measurement of cost, quality, and
      intensity at the level of each nurse and patient across many different settings
      which can be used to inform operational and clinical decision making. In this
      article, the initial results and recommendations of an expert panel tasked with
      defining and measuring nursing care value as part of a larger effort to address
      evolving issues related to big data and nursing knowledge development are
      described.

PMID- 26214934
TI  - Measurement of Nursing's Complex Health Care Work: Evolution of the Science For
      Determining the Required Staffing For Safe and Effective Patient Care.
AB  - The availability of technology to monitor and manage data increases our ability
      to better understand the processes and outcomes needed for patient care. It is
      important to remember this work requires not only the science of data management,
      but also the art of integrating the multiple variables involved in the dynamic of
      safe staffing. Fasoli and Haddock (2010) provided an excellent summary of the
      literature. Nurse leaders must be open to new additions to this work and the
      possibility that the essential ingredient of the gold standard for patient
      classification systems (PCS) might still be missing. The goal of a new approach
      to determine time for nurse work was to advance the science of PCS from the
      perspective of the characteristics identified by Fasoli and Haddock.

PMID- 26214935
TI  - Preserving Staffing Resources As a System: Nurses Leading Operations and
      Efficiency Initiatives.
AB  - Nurse leaders have struggled for generations with using the right staff in
      appropriate roles and numbers to optimally cover patient care services and yet
      preserve salary dollars when possible. The Baptist Health system identified
      opportunities to enhance communication across facilities and encouraged
      executives and department leaders to work together to achieve common goals of
      efficiency and quality. Baptist Health created an operations and efficiency
      council with representation from each of the seven hospitals in the system, as
      well as corporate leaders and support staff. Beginning in April 2014, the system
      began consistently exceeding productivity targets and effectively eliminated a
      $30 million dollar salary variance from the spring of 2013.

PMID- 26214936
TI  - Evaluating the Veterans Health Administration's Staffing Methodology Model: A
      Reliable Approach.
AB  - All Veterans Health Administration facilities have been mandated to use a
      standardized method of determining appropriate direct-care staffing by nursing
      personnel. A multi-step process was designed to lead to projection of full-time
      equivalent employees required for safe and effective care across all inpatient
      units. These projections were intended to develop appropriate budgets for each
      facility. While staffing levels can be increased, even in facilities subject to
      budget and personnel caps, doing so requires considerable commitment at all
      levels of the facility. This commitment must come from front-line nursing
      personnel to senior leadership, not only in nursing and patient care services,
      but throughout the hospital. Learning to interpret and rely on data requires a
      considerable shift in thinking for many facilities, which have relied on
      historical levels to budget for staffing, but which does not take into account
      the dynamic character of nursing units and patient need.

PMID- 26214937
TI  - Nine Principles for Improved Nurse Staffing.
AB  - Nurse staffing is complex. Nursing leaders have taken many initiatives to
      incorporate evidence and scientific data into nurse staffing. Midland Memorial
      Hospital (Texas) developed nine principles to improve nurse staffing. The
      principles include budgeting nursing resources and reconciling the position
      control or hiring plan created on a National Database of Nurse-Sensitive Quality
      Indicators 50th percentile for registered nurse hours per patient day. Nursing
      leaders must understand data-driven nurse staffing plans to communicate clearly
      and budget appropriately for nursing resources.

PMID- 26214939
TI  - Beyond a Band-Aid Approach: An Internal Agency Solution to Nurse Staffing.
AB  - The Institute of Medicine (IOM) affirmed that the employment of temporary or per
      diem nurses augments risk to patient safety. The IOM recommends health care
      facilities avoid hiring nurses working from a temporary external agency. The IOM
      recognizes the need for health care facilities to have a plan in place for
      situations when confronted with short staffing, higher acuity, and increased
      patient census. Based on recommendations from the IOM, an internal agency was
      developed in a university-based health care system. Cost savings were realized
      because of the collaborative efforts of human resources to fill vacancies, unit
      management managing their respective budgets by flexing staff based on patient
      census, and the development and implementation of the Enterprise Staffing Pool.

PMID- 26214940
TI  - Nursing-Sensitive Indicators in Ambulatory Care.
AB  - Ambulatory nursing care can be difficult to comprehend in all its complexity. In
      August 2013, the American Academy of Ambulatory Care Nursing commissioned a task
      force to identify nursing-sensitive indicators specific to ambulatory care
      settings. Given the great variation in settings, staff mix, patient populations,
      role dimensions, skill sets, documentation systems, and resources, determining
      metrics that apply across the entire continuum of care is a daunting task.
      However, it is incumbent upon nurse leaders to define the metrics that will
      promote the value of the registered nurse in ambulatory practice and care
      coordination. Once initial measures are identified, piloted, and validated, the
      infrastructure can be created for ongoing benchmarking and collaboration. The
      long-term goal is to leverage professional nursing practice, based in the
      ambulatory care setting, to improve quality, safety, and cost in health care.

PMID- 26214941
TI  - Hours per Patient Day: Not the Problem, Nor the Solution.
AB  - Hours per patient day (HPPD) is a metric that is easy to use in determining
      budgeted FTE and in comparing staffing across organizations. There are many
      considerations in determining the appropriate HPPD. The combination of automated
      patient acuity, staffing, and human resource systems provide a wealth of
      information for determining the budgeted HPPD and in making defensible requests
      for adjustments in HPPD. No matter how much data we have about staffing levels,
      nurse education and skill levels, the environment of care, or patient acuity, the
      real key is determining the outcomes we need to compare staffing against. We must
      quantify the savings associated with positive outcomes and get this information
      in the hands of the public so they can make informed decisions.

PMID- 26214942
TI  - TELEHEALTH - HAS ITS TIME ARRIVED?

PMID- 26214943
TI  - TELEHEALTH AND TELEMEDICINE TODAY.

PMID- 26214945
TI  - WHY DID HE DO THAT?--A GUIDE TO UNDERSTANDING ALMOST ANYBODY. .

PMID- 26214944
TI  - TIME CAN MARK THE DIFFERENCE BETWEEN LIFE AND DEATH.

PMID- 26214946
TI  - PHYSICIAN TURNOVER: A COSTLY PROBLEM.

PMID- 26214947
TI  - REIMBURSEMENT, NETWORKS AND DEBT: NAVIGATING THE HEALTH INSURANCE MARKETPLACE.

PMID- 26214948
TI  - PHYSICIANS: WILL GETTING RID OF THE ACA CURE WHAT AILS YOU?

PMID- 26214949
TI  - WORKPLACE WELLNESS PROGRAMS RIGHT OR WRONG?

PMID- 26214951
TI  - MINDFULNESS MATTERS: A POWERFUL RESOURCE FOR OVER-STRESSED PHYSICIAN LEADERS.

PMID- 26214950
TI  - THE ECONOMIC IMPACT OF MEDICAL SCRIBES IN HOSPITALS.

PMID- 26214952
TI  - USING ADVANCE PRACTICE REGISTERED NURSES AND PHYSICIAN ASSISTANTS TO EASE
      PHYSICIAN SHORTAGE.

PMID- 26214953
TI  - EMERGENCY DEPARTMENT MEDICAL STAFF FACILITATORS PLAY KEY ROLES.

PMID- 26214954
TI  - Some medical societies would make lousy students.

PMID- 26214955
TI  - Think Tank: Clinical Data Analytics. Solving data analytics delivery problems.

PMID- 26214956
TI  - Healthcare IT's future. Is it mobile and wearable?.

PMID- 26214957
TI  - The questions you should ask about your EHR/EMR.

PMID- 26214958
TI  - LIS trends for 2015 and beyond. How will the laboratory information system adapt
      to the restructuring of healthcare?

PMID- 26214959
TI  - Simplifying RAC audit issues.

PMID- 26214960
TI  - Viewing patient data holistically. A modular collaboration platform is the key.

PMID- 26214961
TI  - TOO MANY MEDICS. Why we don't need Johnny & Roy on steroids.

PMID- 26214962
TI  - HEMORRHAGE CONCERNS.

PMID- 26214963
TI  - Authors Dennis Filips, MD & Joe Holley, MD, FACEP, respond.

PMID- 26214964
TI  - STAYING ON TOPIC. Be productive with your meeting time & agenda.

PMID- 26214965
TI  - CAR VS. TREE. Which came first, the trauma or the STEMI?

PMID- 26214966
TI  - BLOOD PRESSURE RESCUE. Treat hypotension without IV fluids.

PMID- 26214967
TI  - TXA in the USA. Tranexamic acid's potentially bright future relies on
      collaborative data.

PMID- 26214968
TI  - Medical waste. Dispelling the stigma of trash generated by healthcare providers.

PMID- 26214969
TI  - Australia's flying doctors. How the world's largest aeromedical response service
      provides effective patient retrieval in the Outback.

PMID- 26214970
TI  - Resuscitating the heartmobile. The nation's first ALS response vehicle is
      restored to preserve its place in EMS history.

PMID- 26214971
TI  - Pediatric deficiencies. How can we improve proficiency in pediatric patient care?

PMID- 26214972
TI  - Accountable care. Understanding EMS' role in the chain of care.

PMID- 26214973
TI  - Managing patient-centric care. Montgomery County, Texas, community paramedicine
      program sees early success.

PMID- 26214974
TI  - Scorched skin. A guide to prehospital burn management.

PMID- 26214975
TI  - CLOSING THE GAP. The intersection of EMS & public health.

PMID- 26214976
TI  - FLYING BLIND. Staying composed while 'meeting the Mexican ambulance'.

PMID- 26214977
TI  - WHAT MATTERS. For veterans, it's still a war out there.

PMID- 26214978
TI  - It can make nurses sick. Aiming to prevent incivility, bullying, violence.

PMID- 26214979
TI  - Medicare payment 'fix' includes key provisions for nurses.

PMID- 26214980
TI  - To eat or not to eat? Nurses offer healthy advice to colleagues and their
      patients.

PMID- 26214981
TI  - Mitigating the risks of emotional labor.

PMID- 26214982
TI  - Florida nurse's triple aim. Exploring stress-related interventions for
      immigrants, strengthening minority workforce, developing health disparity
      researchers.

PMID- 26214983
TI  - An innovative leader aimed at developing the best and brightest.

PMID- 26214984
TI  - Who's smiling now?

PMID- 26214985
TI  - HISTORY OF OTOSURGERY - THE 20th CENTURY HISTORY OF MASTOID SURGERY AND
      TYMPANOPLASTY.

PMID- 26214986
TI  - IMMUNOHISTOCHEMICAL EXPRESSION OF P16INK4a IN INFLAMMATORY, PRENEOPLASTIC AND
      NEOPLASTIC CERVICAL LESIONS.
AB  - INTRODUCTION: High-risk human papilloma viruses play a main role in the
      development of cervical dysplasias and carcinomas. p16INK4a can be considered as
      a surrogate marker of active high-risk human papillomaviruses infection in
      dysplastic and neoplastic cells of the cervix. This study was aimed at
      determining the presence and level of pl6INK4a expression in inflammatory,
      preneoplastic and neoplastic lesions of the cervix. MATERIAL AND METHODS: The
      study was performed on 109 samples of cervical biopsy. Cervical cancer was
      diagnosed in 36 patients, 34 patients had a preneoplastic change (dysplasia) in
      stratified squamous cervix epithelium and a nonspecific inflammatory process was
      found in 39 patients. In all samples, immunohistochemical analysis using
      antibodies to pl6INK4a was performed. RESULTS: The expression of pl6INK4a was
      verified in all cases of cervical cancer (100%), in 67.65% of dysplastic cervical
      lesions and in 38.5% of inflammatory lesions. A statistically highly significant
      difference was found in the presence and level of expression among neoplasic,
      dysplastic and inflammatory lesions of the cervix (chi2 = 76.02, p <0.001). The
      expression was more frequent and had a higher level in neoplastic and high grade
      dysplastic lesions compared to expression in inflammatory lesions and low grade
      dysplasias. CONCLUSION: The analysis of the presence of pl6INK4a can
      differentiate non-neoplastic, high grade preneoplastic and neoplastic changes of
      the cervix. The use of pl6INK4a in interpreting borderline lesions of the cervix
      can enable a rational theraDeutic treatment of patients.

PMID- 26214987
TI  - ANALYSIS OF DIFFERENCES IN BLOOD PRESSURE OF WOMEN BELONGING TO DIFFERENT AGE
      GROUPS.
AB  - INTRODUCTION: One of the risk factors for the occurrence of arteriosclerosis and
      coronary heart diseases is physical inactivity. Together with hypokinesia,
      excessive feeding, age and other factors, make a multifactorial cause of
      cardiovascular disease. Positive effects of physical activities have been proved
      in the primary, secondary and tertiary prevention of coronary heart diseases.
      MATERIAL AND METHODS: This study included 119 women from 20 to 76 years of age.
      All subjects vere nonsmokers who did not have a cardiovascular disease, and were
      divided into five different age groups. Systolic and diastolic blood pressure was
      measured by the digital blood pressure measuring device with cuff OMRON M4-1. The
      evaluation of blood pressure was performed at the Faculty of Sport and Physical
      Education in Novi Sad. The data processing was done by the statistical package
      SPSS 20.0. RESULTS: According to the obtained data it can be concluded that there
      are statistically significant differences in both individual and general system
      of the observed variables in different age groups. In addition, there are
      statistically significant differences between pairs of groups, which were
      observed when comparing with the oldest age group. CONCLUSION: The programmes of
      prevention and control of cardiovascular diseases should decrease the influence
      of risk factors and improve diagnostics and therapy of cardiovascular diseases.

PMID- 26214988
TI  - THE LEVEL OF GRAMMAR SCHOOL STUDENTS' KNOWLEDGE ON CARDIOVASCULAR DISEASE RISK
      FACTORS.
AB  - INTRODUCTION: Cardiovascular diseases are one of the leading causes of mortality
      and morbidity worldwide. The atherosclerotic process in the aorta starts in
      childhood, while atheroclerotic changes of coronary heart vessels start in
      adolescence. The aim of the study was to evaluate the knowledge of the students
      attending all four grades of grammar school about the risk factors for
      cardiovascular disease, with special attention to the risk factors that can be
      influenced by modification of life-style. MATERIAL AND METHODS: Data from the
      entrance and exit tests were collected from 197 students attending a grammar
      school in Novi Sad. Chi-square test and Student T-test or Mann-Whitney U test
      were used to examine the statistical difference between categorized variables and
      the continuous variables, respectively. RESULTS: The difference between the
      number of correct answers for all the students on the entrance test and exit test
      was statistically significant (p<0.0005) and the overall knowledge level after
      lectures was increased by 29.4%. The lowest level of knowledge on the entrance
      tests was noted among the students of the third grade of grammar school and after
      the lectures, the student's knowledge level was increased by 82.3% (p<0.0005).
      CONCLUSION: Children and adolescents from Vojvodina and Serbia should be well
      informed about the cardiovascular disease risk factors and their prevention with
      special attention paid to the risk factors that can be influenced by changing
      lifestyle habits.

PMID- 26214989
TI  - ASSESSMENT OF QUALITY OF LIFE IN PATIENTS AFTER LOWER LIMB AMPUTATION.
AB  - INTRODUCTION: Lower extremity amputation is a surgical procedure resulting in
      important anatomical, functional, psychological, and social consequences that can
      influence the quality of life of these patients. The aim of this research was to
      compare the quality of life of patients with lower extremity amputation and
      people without amputation taking into account gender differences as well as the
      amputation level. MATERIAL AND METHODS: The study was designed as a cross
      sectional study which included 56 subjects. The patients from the experimental
      group underwent prosthetic rehabilitation treatment at the Department of Medical
      Rehabilitation, Clinical Centre of Vojvodina. The experimental group included 28
      patients (21 male, 7 female) with lower extremity amputation, their average age
      being 65.36+/-13.64. The control group consisted of 28 age and gender matching
      subjects without amputation. Research ANd Development (RAND) 36--Item Health
      Survey 1.0 (SF-36) was used to measure the quality of life. RESULTS: The results
      showed that patients with lower extremity amputation scored lower than the
      control group on all SF-36 variables (p<0.05). None of the SF-36 variables
      differed between the genders (p>0.05). Seventeen (61%) patients were with
      transfemoral, and 11 (39%) with transtibial level of amputation. The patients
      with transtibial amputations scored higher on physical functioning and general
      health status variables (p<0.05). CONCLUSION: The patients with lower extremity
      amputations have numerous limitations compared to the control group, regardless
      of gender, while the patients with lower level of amputation have a higher level
      of physical functioning.

PMID- 26214990
TI  - RELIABILITY OF POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY IN EVALUATION OF
      TESTICULAR CARCINOMA PATIENTS.
AB  - INTRODUCTION: The study was aimed at assessing the reliability of 18F
      fluorodeoxyglucose positron emission tomography-computed tomography scan in
      evaluation of testicular carcinoma patients. MATERIAL AND METHODS: The study
      sample consisted of 26 scans performed in 23 patients with testicular carcinoma.
      According to the pathohistological finding, 14 patients had seminomas, 7 had
      nonseminomas and 2 patients had a mixed histological type. In 17 patients, the
      initial treatment was orchiectomy+chemotherapy, 2 patients had
      orchiectomy+chemotherapy+retroperitoneal lymph node dissection, 3 patients had
      orchiectomy only and one patient was treated with chemotherapy only. Abnormal
      computed tomography was the main cause for the oncologist to refer the patient to
      positron emission tomography-computed tomography scan (in 19 scans), magnetic
      resonance imaging abnormalities in 1 scan, high level oftumor markers in 3 and 3
      scans were perforned for follow-up. Positron emission tomography-computed
      tomography imaging results were compared with histological results, other imaging
      modalities or the clinical follow-up of the patients. RESULTS: Positron emission
      tomography-computed tomography scans were positive in 6 and negative in 20
      patients. In two patients, positron emission tomography-computed tomography was
      false positive. There were 20 negative positron emission omography-computed
      tomography scans perforned in 18 patients, one patient was lost for data
      analysis. Clinically stable disease was confirmed in 18 follow-up scans performed
      in 16 patients. The values of sensitivty, specificity, accuracy, and positive-
      and negative predictive value were 60%, 95%, 75%, 88% and 90.5%, respectively.
      CONCLUSION: A hgh negative predictive value obtained in our study (90.5%)
      suggests that there is a small possibility for a patient to have future relapse
      after normal positron emission tomography-computed tomography study. However,
      since the sensitivity and positive predictive value of the study ire rather low,
      there are limitations of positive positron emission tomography-computed
      tomography scan to suggest persistent disease.

PMID- 26214991
TI  - INFLUENCE OF DIFFERENT LEVELS OF SPORTS ACTIVITIES ON THE QUALITY OF LIFE AFTER
      THE RECONSTRUCTION OF ANTERIOR CRUCIATE LIGAMENT.
AB  - INTRODUCTION: The goal of this study was to examine the nature and presence of
      influence of different levels of sports activity on the life quality of the
      patients a year after the reconstruction of anterior cruciate ligament. MATERIAL
      AND METHODS: The study included 185 patients operated at the Department of
      Orthopedic Surgery and Traumatology of the Clinical Centre of Vojvodina, who were
      followed for twelve months. Data were collected using the modified Knee Injury
      and Osteoarthritis Outcome Score questionnaire which included the Lysholm scale.
      RESULTS: This study included 146 male and 39 female subjects. The reconstruction
      of anterior cruciate ligament was equally successful in both gender groups. In
      relation to different types of sports activity, there were no differences in the
      overall life quality measured by the questionnaire and its subscales, regardless
      of the level (professional or recreational). However, regarding the level of
      sports activities, there were differences among the subjects engaged in sports
      activities at the national level as compared with those going in for sports
      activities at the recreational level, and particularly in comparison with
      physically inactive population. A significant correlation was not found by
      examining the aforementioned relationship between sports activities. CONCLUSIONS:
      This study has shown that the overall life quality a year after the
      reconstruction of the anterior cruciate ligament does not differ in relation to
      either the gender of the subjects or the type of sports activity, while the level
      of sports activity does have some influence on the quality of life. Professional
      athletes have proved to train significantly more intensively after this
      reconstruction than those going in for sports recreationally.

PMID- 26214992
TI  - CHIKUNGUNYA - A SERIOUS THREAT FOR PUBLIC HEALTH.
AB  - INTRODUCTION: Chikungunya is a contagious disease caused by Chikungunya virus, an
      arbovirus from the Togaviridae family. This infection is mostly spread by
      mosquitoes from the genus Aedes, especially Aedes albopiclus, which have spread
      from Asia to America and Europe including some countries surrounding Serbia.
      EPIDEMIOLOGIC FEATURES: The outbreak of epidemics has been reported in
      Philippines, Sumatra, Java, Indonesia, West Africa region (from Senegal to
      Cameroon), Congo, Nigeria, Angola, Uganda, Guinea, Malawi, Central African
      Republic, Burundi, South Africa and India. At the beginning of the 21st century,
      large outbreaks were recorded on the island of Reunion. During 2006, 1.400.000
      cases of chikungunya infection were recorded in India. Local transmission of
      infection in continental Europe was reported from Northeast Italy (254 suspected
      and 78 laboratory confirmed cases in Emilia-Romagna region) and France (two cases
      in 2010). From December 2013 to June 2014, 5.294 confirmed cases and more than
      180.000 suspected cases of chikungunya were reported in the Caribbean. CLINICAL
      FINDINGS: The disease presents suddenly with fever, rush and arthralgia. In
      general, chikungunya is a mild self - limited disease. Less often, it may be
      presented with signs of meningoencephalitis or fulminant hepatitis, sometimes
      with fatal outcome. CONCLUSION: Fast developing international traffic and booming
      tourism as well as the vector spreading from its homeland make chikungunya a real
      threat to our country.

PMID- 26214993
TI  - FROM ANEURYSMAL BONE CYST TO TELANGIECTATIC OSTEOSARCOMA WITH METASTASIS IN
      INGUINAL LYMPH NODES - CASE REPORT.
AB  - INTRODUCTION: Aneurysmal bone cyst is a benign bone lesion composed of blood
      filled cystic cavities lined by fibrous septa. Its malignant transformation of is
      a rare event. CASE REPORT: We report a case of a lesion in the second metatarsal
      bone in a 29-year-old male, presented as a slight swelling of the right foot.
      After the curettage had been done, the diagnosis of aneurysmal bone cyst was made
      but the recurrence occurred 4 years later. The biopsy of the recurrent tumor
      showed compact neoplastic tissue consistent with diagnosis of giant cell tumor
      with malignancy. The malignant component was recognized as a high grade sarcoma
      with osteoid production. A tumor mass with the whole II metatarsal bone was
      extirpated and a resected part of fibula was transplanted. A year later, another
      recurrence occurred, an amputation was performed and a teleangiectatic
      osteosarcoma with ingvinal lymph nodes metastases was diagnosed. No other tumor
      mass was confirmed, either clinically or by imaging techniques at the time of his
      third operation. He died 4 months later with multiple pulmonary metastases.
      CONCLUSION: We emphasize the importance of team work in order to achieve the
      accurate diagnosis, highlighting careful radiological examinations, good sampling
      and awareness of unusual cases in bone tumor pathology.

PMID- 26214994
TI  - PYODERMA GANGRENOSUM IN BURNED PATIENT - CASE REPORT.
AB  - INTRODUCTION: Pyoderma gangrenosum is a rare, chronic, destructive, ulcerating
      skin disease of uncertain etiology. It develops most frequently in patients
      between 25-45 years of age and affects both sexes equally. CASE REPORT: We
      present a case of pyoderma gangrenosum in a young female patient who sustained a
      burn injury of 40% total body surface area. She underwent four operations. She
      developed a wound infection and urinary infection during her hospital stay. By
      the end of hospitalization, the papules followed with coalesce of ulcerations
      formed on the previously epithelized areas of her legs. The patient complained of
      the intensive pain localized on these surfaces. Since pyoderma gangrenosum was
      suspected, a dermatologist was included in treatment. Therapy was initiated
      (methylprednisolone 60 mg per day intravenously) with gradual reduction of the
      dosage. The patient was discharged from hospital two weeks later with almost
      fully complete cicatrization and epithelization. CONCLUSION: Pyoderma gangrenosum
      is still difficult to be diagnosed in the absence of specific and sensitive
      diagnostic methods; however, it is crucial to be suspected as early as possible
      and to start treatment immediately. Multidisciplinary approach is essential for
      ontimal results.

PMID- 26214995
TI  - DEFINITE MANAGEMENT OF BILATERAL LOWER LEG NONUNION FRACTURES BY ILIZAROV
      APPARATUS IN POLYTRAUMATIZED PATIENT - CASE REPORT.
AB  - INTRODUCTION: Nonunion of long bones may often be associated with significant
      function loss of affected extremity, joint stiffness, and even extremity
      amputation or systemic manifestations in the case of infection. The aim of this
      case report is to highlight the possibilities of Ilizarov apparatus in the
      treatment of fracture nonunions of both lower legs treated by different operative
      methods and to show that it is not necessary to remove osteosynthetic material
      (intramedullary nail) in every case when nonunion occurs to achieve its recovery.
      CASE REPORT: A 62 year-old man was injured in a traffic accident as a pedestrian
      in April2012, when he experienced polytrauma, including shaft fracture of the
      right femur, and segmental open fractures of the right (Gustillo-Anderson grade
      I) and left (Gustillo-Anderson grade II) lower leg. The fractures of right femur
      and right tibia were stabilized initially with intramedullary nails, while the
      left lower leg fracture was treated by unilateral external fixator. After 5
      months, there were no clinical and radiographic signs of union on lower legs,
      therefore the patient underwent re-surgery. Ilizarov apparatus was applied on
      both lower legs. The patient was early verticalized and both apparatus were
      removed after 4 months. According to the modified protocol of the Association for
      the Study and Application of Methods of Ilizarov, the lower leg bony results were
      good and excellent, and the functional results were excellent on both sides.
      CONCLUSION: Nonunion fracture of the right lower leg initially treated by the
      method of intramedullary osteosynthesis and afterwards by placing Ilizarov
      apparatus shows that in some cases it is not indicated to remove fixative
      material in order to achieve full recovery of fracture, thus eliminating the
      danger of all negative effects resulting from the classical extensive surgical
      treatment.

PMID- 26214996
TI  - Pulmonary oedema producing toxin from Mesobuthus tamulus venom augments cardio
      respiratory reflexes through B2 kinin receptors.
AB  - The current study was undertaken to compare the effects of pulmonary oedema
      producing toxin (PO-Tx) isolated from Mesobuthus tamulus venom on cardio
      respiratory reflexes with exogenously administered bradykinin (BK) and to
      delineate the type of BK receptors mediating these responses. Jugular venous
      injection of phenyldiguanide (PDG) in anaesthetized rats produced reflex
      bradycardia, hypotension and apnoea. The PDG-induced reflex was augmented (two
      folds) by PO-Tx. The pulmonary water content in PO-Tx treated group was also
      increased. The PO-Tx-induced reflex changes as well as pulmonary oedema were
      blocked by-Hoe-140 implicating the involvement of B2 kinin receptors. Exogenous
      BK also produced augmentation (two folds) of the PDG-induced reflexes and
      increased the pulmonary water content. The BK-induced augmentation was blocked by
      pre-treatment with des-Arg10 Hoe 140 (a B1 receptor antagonist) and Hoe 140 (B2
      receptor antagonist). However, these antagonists did not prevent the development
      of BK-induced pulmonary oedema. Present results indicate that PO-Tx augmented the
      PDG-induced reflex responses similar to BK and the PO-Tx induced augmentation of
      reflexes is mediated through B2 receptors.

PMID- 26214997
TI  - Effect of Orexin-A infusion in to the Nucleus Accumbens on consummatory behaviour
      and alcohol preference in male Wistar rats.
AB  - BACKGROUND: Effect of administration of Orexin-A into nucleus accumbens (NAcc) in
      relation to the regulation of feeding behavior and alcohol consumption at
      specific time intervals is relatively unknown. MATERIALS AND METHODS: In this
      study, Male Wistar albino rats (n = 54) weighing about 250 +/- 10 grams were
      implanted bilaterally with guide cannula (22 gauze) to target NAcc by stereotaxic
      surgery. Saline (0.9%) for control and Orexin-A for experimental groups (100 pmol
      or 250 pmol) were infused by Harvard picoplus pump. Food, water and alcohol (10%)
      consumption were measured at 1, 2, 4 and 24 hours to evaluate the effect of
      Orexin-A in fasted rats (24 hours). Preference study was carried out by two
      bottle choice test. RESULTS: Orexin-A infusion into NAcc showed significant
      increase in food at 1 hr in all groups compared to controls (p < 0.05) and
      alcohol (p < 0.02) intake. The changes were dose dependent. There was no
      noticeable preference or alcohol. CONCLUSIONS FOR: These findings showed that
      Orexin-A in NAcc could be involved in feeding and drinking but not alcohol
      preference. The results highlight the effect of Orexin A infusion into NAcc in
      consummatory behaviour besides other hypothalamic and mesolimbic centres.

PMID- 26214998
TI  - Influence of genetic variability at the ACE locus in intron 16 on Diabetic
      Nephropathy in T1DM patients.
AB  - BACKGROUND: Diallelic [insertion/deletion (L/D)] polymorphism in the angiotensin
      converting enzyme (ACE) gene has been reported inconsistently as being associated
      with risk of diabetic nephropathy (DN). OBJECTIVE: To examine the three ACE poly
      morphic variants in intron 16 for a possible role in modulating DN in T1DM
      patients from Kutch region, Gujarat. DESIGN AND SETTING: I/D polymorphism in
      intron 16 of the ACE gene was examined in a case-control group (280 participants
      with T1DM, case participants n = 138; control participants n = 142) for
      association with nephropathy. All recruited individuals were carefully phenotyped
      and genotyping was performed using polymerase chain reaction and gel
      electrophoresis methods. Suitable descriptive statistics was used for different
      variables. RESULTS: No departure from Hardy-Weinberg equilibrium was observed in
      cases or controls. Genetic polymorphism at the ACE locus in intron 16 were
      significantly associated with nephropathy when analyzed either by genotype or
      allele frequencies and D/D variant were significantly (p = 0.0002) associated
      with nephropathy at the 5% level. In multivariate analysis, D/D variant had an
      independent and strongest influence on the micro-albumin excretion (p = 0.002, OR
      = 2.11, 95% CI = 1.26-4.48). However, it did not independently change the odds of
      having macroalbuminuria versus microalbuminuria. CONCLUSION: Genotype-associated
      differences in ACE in intron 16, have functional consequences in genetic
      susceptibility to diabetic nephropathy in a population with T1DM, and thus
      represent a potential DN genetic susceptibility locus worthy of replication.

PMID- 26214999
TI  - Effect of intrapleural oxytocin injection on blood glucose level in rat (rattus
      norvegicous).
AB  - BACKGROUND AND PURPOSE: The effect of Oxytocin on energy metabolism is still
      question. The aim of the present study was to investigate the effect of exogenous
      oxytocin injection in different dose and timetable on blood glucose level in rat.
      EXPERIMENTAL APPROACH: In this study 16 adult female rats were divided into 2
      groups (Treatment 1(T1) and Treatment 2(T2)). T1 with 8 adult female rats
      received 0.2 IU/Kg oxytocin via intrapleural (IP) and blood glucose level was
      tested at 0th, 20th, 40th and 60th min after injection by collecting the blood
      from jugular vein. In T2 eight female rats received 0.4 IU/kg oxytocin via IP
      taking blood glucose measure at the same minutes as T1. The experiment tested in
      three replicates. Blood glucose meter (Model: 3TMSO1G) was used with glucose
      smart blood glucose monitoring system to the measurement of blood glucose level
      in rats. Data were analyzed using the GLM procedure of SAS (SAS, version 9) PDIFF
      was used to compare least square means among treatments adjusting by tukey test.
      KEY RESULTS: There were hypoglycemic tendency in the changes of the blood glucose
      level in both T1 and T2, 20th min after injection (88.79 +/- 3.28, 68.58 +/-
      3.63, respectively), while in the remaining subjects (4th and 60th min) blood
      glucose level increased (115.54 +/- 4, 79.7 +/- 2.09 and 136.33 +/- 5.8, 123.54
      +/- 0.9, respectively). These results showed that blood glucose level in T1
      significantly higher than T2 (p < 0.0001). CONCLUSIONS AND IMPLICATIONS: These in
      vivo results showed that exogenous oxytocin can be good choice to decrease the
      blood glucose level very fast.

PMID- 26215000
TI  - Beneficial effect of Omega-3 polyunsaturated fatty acids on neurosensorial
      impairments and oxidative status in Streptozotocin induced diabetic rats.
AB  - OBJECTIVES: The present study evaluated the beneficial effects of omega 3 PUFA
      present in fish oil on neurosensorial impairments, namely learning, memory and
      anxiety in Streptozotocin (STZ) induced diabetic rats. The brain homogenate was
      analysed for oxidative status following Omega 3 PUFA treatment. METHODS: Male,
      Wistar rats of 2-3 months old were divided into non diabetic controls, diabetic
      control, & fish oil treated diabetic rats (n = 6). Diabetes was induced by
      injection of STZ (48 mg/kg, ip). Animals were treated orally for 30 days with a
      dose in each group of 0.5 g/kg/day of fish oil. All experiments were conducted
      after ethical committee clearance was obtained. RESULTS: Memory and exploratory
      behavior were improved (p < 0.01) in fish oil treated rats as compared with
      diabetic rats. A significant (p < 0.001) decrease in MDA and a significant
      increase (p < 0.001) in total antioxidant level (TAO) were observed in fish oil
      treated rats. CONCLUSION: Omega 3 PUFA present in fish oil could be used an
      adjuvant therapy for treatment and prevention of neurosensorial impairment in
      diabetes mellitus.

PMID- 26215001
TI  - Correlation between lipid profile & carotid intima media thickness in cerebral
      ischemia.
AB  - Cerebrovascular accident or stroke is defined by an abrupt onset of neurological
      deficit that is attributable to a focal vascular cause. Stroke is a major cause
      of morbidity and mortality worldwide. This may result from brain infarction or
      hemorrhage. Carotid atherosclerosis is a reasonable risk factor for cerebral
      ischemic stroke. Deranged lipid metabolism due to various modifiable and non
      modifiable risk factors leads to the pathogenesis of atherosclerosis. This study
      is intended to find out any association between altered lipid metabolism
      (Cholesterol, Triglycerides, LDL : HDL ratio) and development of cerebral
      ischemia. An observational case control study was conducted with 50 cases of
      cerebral ischemia and 50 age & sex matched healthy controls within age group 50
      70 years. After inclusion of cases and controls and taking informed consent they
      underwent history taking, proper clinical examination & biochemical
      investigations (lipid profile). Then data were collected and results were
      statistically analyzed using Chi-square test & Independent Sample "T-test". The
      study showed altered lipid profile is associated with cerebral ischemia by
      increasing carotid intima media thickness (IMT). There was significant (p <
      0.001) dyslipidemia (NCEP ATP III guidelines) in cases as compared to controls.
      Hence early diagnosis and monitoring of dyslipidemia and treatment of the high
      risk group with anti hyperlipidemic drugs will help to prevent the incidence of
      cerebral ischemic stroke thereby reducing morbidity and mortality.

PMID- 26215002
TI  - Physical exercise and cardiac autonomic activity in healthy adult men.
AB  - Physical inactivity is an important risk factor for cardiovascular mortality and
      morbidity. Regular exercise is known to improve health and maintain physical
      fitness. The heart rate response to exercise reflects autonomic control of heart
      and has shown to predict cardiovascular prognosis. Decreased heart rate
      variability (HRV) is known as a risk factor for cardiovascular mortality. The
      objective of this study was to study the effect of exercise on cardiac autonomic
      activity. Thirty two healthy adult men in the age group of 18-25 years with
      normal body mass index (BMI) were recruited from different physical fitness
      centers, who were undergoing regular exercise for past 3 months. Resting ECG was
      recorded for 5 minutes and analyzed for frequency analysis of HRV. HRV parameters
      of the subjects were compared with fifty age and BMI matched subjects who were
      not undergoing any exercise program. Physical activity level of all subjects was
      assessed by using Global Physical Activity Questionnaire. The exercising (E)
      subjects were found to have a lesser heart rate (73.27 +/- 8.6 vs 74.41 +/- 8.59)
      compared to non-exercising (NE) group, which was not significant. No significant
      difference was found in frequency domain parameters of HRV between exercising and
      non-exercising group with LF (47.12 +/- 19.17 vs 43.55 +/- 16.66), HF (41.03 +/-
      17.65 vs 46.03 +/- 15.89) and LF/HF (1.61 +/- 1.16 vs 1.22 +/- 0.93)
      respectively. Physical activity level was significantly different between the two
      groups (4175 +/- 1481.53 vs 1176.4?1103.83, p<0.001). This study showed 3 months
      of exercise did not have any effect on cardiac autonomic activity despite the
      difference in physical activity.

PMID- 26215003
TI  - Protective role of ascorbic acid in hemorrhage-induced cardiovascular depression.
AB  - Haemorrhagic shock is associated with hyperproduction of free radicals. Hence
      ascorbic acid (AA), a free radical scavenger, may be of benefit in such cases. We
      investigated in Wistar rats the role of free radicals in causing cardiovascular
      depression and the protective role of ascorbic acid, if any, in acute
      haemorrhage. The rats were catheterized for recording hemodynamic parameters.
      Acute haemorrhage was induced through phlebotomy followed by resuscitation. The
      test group received AA for 3 days before inducing haemorrhage and was
      resuscitated with AA and Ringer's lactate. The controls received only ringer
      lactate. Malondialdehyde was estimated to assess free-radical production. All
      rats showed significant fall in cardiovascular parameters with simultaneous
      increase in MDA level. While all rats showed significant improvement following
      resuscitation, the recovery was greater in the test group. The MDA levels
      decreased significantly in the ascorbic acid treated group. Our results
      demonstrate the involvement of free radicals in hemorrhage-induced cardiovascular
      depression and the cardio-protective effect of ascorbic acid.

PMID- 26215004
TI  - Long-term stay at low altitude (1,200 m) promotes better hypoxia adaptation and
      performance.
AB  - Acute exposure to high altitude hypoxia is known to decrease physical
      performance. The exercise performance increases during moderate altitude training
      (2000-3000 m) but benefits are overshadowed by adverse effect associated with
      hypoxia. Therefore, the study was designed to address whether low altitude of
      1200 m could increase exercise performance without any adverse effects and a
      correlation with stay period (stay > 6 month) was optimized. In the present study
      residents of lower altitude (1200 m altitude) (LA) and sea level (SL) residents
      were subjected to sub-maximal exercise test and their exercise response in terms
      of post-exercise heart rate and change in oxygen saturation was compared. Post
      exercise peak heart rate (129.89 +/- 13.42 vs 146.00 +/- 11.81, p < 0.05) was
      significantly lower and arterial oxygen saturation (SpO2) after exercise had a
      significant fall (95.3 +/- 2.26% vs 98 +/- 0% p < 0.001) in LA residents. The
      hematological parameters like hemoglobin (Hb) and hematocrit (Hct) taken as
      markers of physiological adaptation, were also found to be significantly higher
      in LA as compared to SL residents (Hb 16.13 +/- 0.70 vs 14.2 +/- 0.87, p < 0.001
      and Hct 47.4 +/- ?2.08 vs 44.0 +/- ?0.72, p <0.001). Overall, the study
      highlights that physiological adaptation at 1200 m results into a better exercise
      response and hematological benefit compared to sea level residents.

PMID- 26215005
TI  - Age and gender might influence big five factors of personality: a preliminary
      report in Indian population.
AB  - Age and gender are two important physiological variables which might influence
      the personality of an individual. The influence of age and gender on big five
      personality domains in Indian population was assessed in this cross-sectional
      study that included 155 subjects (female = 76, male = 79) aged from 16-75 years.
      Big five personality factors were evaluated using 60-item NEO-Five Factor
      Inventory (NEO-FFI) at a single point in time. Among the big five factors of
      personality, Conscientiousness was positively correlated (r = 0.195; P < 0.05)
      with age in total study population, and retained the significance (P < 0.05) in
      men only when analyzed by gender subgroups. Further, age and gender sub-group
      analysis also showed that Neuroticism was inversely correlated with age in women
      aged 26-35 years (P < 0.05). Neuroticism and Extraversion showed a positive
      correlation with age in men aged 36-45 years (P < 0.001 and P < 0.05,
      respectively). Neuroticism was inversely correlated with age in men aged 46-55
      years (P < 0.05). This preliminary report suggested that personality traits might
      change with age, and is gender-dependent.

PMID- 26215006
TI  - Effect of dual task activity on reaction time in males and females.
AB  - The present study was designed to compare the auditory and visual reaction time
      on an Audiovisual Reaction Time Machine with the concomitant use of mobile phones
      in 52 women and 30 men in the age group of 18-40 years. Males showed
      significantly (p < 0.05) shorter reaction times, both auditory and visual, than
      females both during single task and multi task performance. But the percentage
      increase from their respective baseline auditory reaction times, was more in men
      than women during multitasking, in hand held (24.38% & 18.70% respectively) and
      hands free modes (36.40% & 18.40% respectively) of the use of cell phone. VRT
      increased non significantly during multitasking in both the groups. However, the
      multitasking per se has detrimental effect on the reaction times in both the
      groups studied. Hence, it should best be avoided in crucial and high attention
      demanding tasks like driving.

PMID- 26215007
TI  - Effect of mobile usage on serum melatonin levels among medical students.
AB  - Exposure to extremely low frequency (ELF) electromagnetic radiations from mobile
      phones may affect the circadian rhythm of melatonin in mobile users. The study
      was designed with objective to evaluate the influence of mobile phone on
      circadian rhythm of melatonin and to find the association if any between the
      hours of mobile usage with serum melatonin levels. All the volunteers medical
      students using mobiles for > 2 hrs/day were included in high users group and
      volunteers who used mobile for <= 2 hrs where included in low users group. Both
      high and low users volunteers were sampled three times in the same day (Morning-3
      4 am, Noon 1-2 pm, Evening-5-6 pm) for estimation of serum melatonin levels:
      Comparsion of sernum melatonin levels in high users and low users were done by
      Mann Whitney "U" Test. Reduced morning melatonin levels (3-4 am) was observed in
      high users (> 2 hrs/day) i.e high users had a disturbed melatonin circadian
      rhythm.There was a negative correlation between melatonin secretion and hours of
      mobile usages.

PMID- 26215008
TI  - Reliability of sexual dimorphism in blood.
AB  - BACKGROUND: Demonstration of sex chromatin forms an important aspect of human
      genetics. It also establishes the interrelationship between sex chromatin and an
      inactive X-chromosome. The term "sex chromatin" in blood refers to the
      "Drumsticks of polymorphonuclear leukocytes" or "Davidson's bodies". OBJECTIVE:
      This correlative study evaluates the presence of these drumsticks quantitatively
      and also highlights the concept of blood chimaerism in humans. METHOD: Leishman
      stained peripheral blood smears from 60 individuals (30 males and 30 females)
      were obtained and studied under bright-field microscope (40X) for presence of
      Drumstick appendages. RESULTS AND CONCLUSION: On comparing mean numbers of
      Davidson's bodies in females and males, an extremely significant correlation (P <
      0.0001) was seen. Hence, it could be surmised that the presence of appendages in
      neutrophils (Drumstick bodies) can be useful in gender differentiation.

PMID- 26215009
TI  - Type 2 diabetes mellitus affects male fertility potential.
AB  - OBJECTIVE: Diabetes is a syndrome that affects all the physiological systems of
      the body, therefore this study was undertaken to compare the seminogram
      parameters in diabetics and non-diabetics. STUDY DESIGN: The study was carried
      out at Male Infertility and Reproductive Physiology unit in the Department of
      Physiology, MGIMS, Sevagram, Wardha. 25 normozoospermic subjects with type 2
      diabetes and 25 normozoospermic non diabetic subjects were recruited in the
      study. The semen samples were analyzed for sperm concentration, motility and
      morphology. RESULTS: In diabetic group the sperm concentration was 24.6
      millions/ml with the motility of 52.3% and normal morphology 31.5%, while in non
      diabetic group the sperm concentration was 42.7 millions/ml with 63.1% motility
      and 47.2% normal morphology. CONCLUSION: Thus our observations indicate that
      there is a detrimental effect of type 2 diabetes mellitus on semen parameters.

PMID- 26215010
TI  - Ethanolic extract of Ficus carica leave Suppresses Angiogenesis by Regulating
      VEGF-A and Integrin beta3 mRNA Expression in Human umbilical vein endothelial
      cells.
AB  - BACKGROUND: In the present study, we investigated the anti-angiogenic effects of
      the ethanol extract of Ficus carica leave on human umbilical vein endothelial
      cells (HUVECs). METHODS: HUVECs were used in this study. The cells were cultured
      in DMEM medium and then incubated with different concentrations of ethanolic
      extract of Ficus carica leave (0-25 MUg?ml) in the presence or absence of the
      extract for 24 hours. Cell viability was analyzed using neutral red assay.
      Endothelial cell tube formation was measured with the Matrigel basement membrane
      matrix. The level of VEGF and Integrin beta3 mRNA expression in the HUVECs was
      measured with reverse-transcription quantitative real-time polymerase chain
      reaction (RT-q real time PCR). RESULTS: We observed that the extract dose
      dependently inhibited the tube formation of HUVECs. Furthermore, the extract
      significantly decreased mRNA expression levels of VEGF-A and Integrin beta3 in
      HUVECs at 20 MUg?ml concentration of the extract compared to untreated control
      cells (P < 0.05). CONCLUSION: Our findings suggest that ethanolic extract of
      Ficus carica leave contains anti-angiogenic activities and could be a candidate
      as a potential agent for the prevention of angiogenesis related disorders.

PMID- 26215011
TI  - Ellagic acid modulates sodium valproate induced reproductive toxicity in male
      Wistar rats.
AB  - This study evaluated the protective effect of ellagic acid on sodium valproate
      induced sperm abnormalities in male Wistar rats. A total of 30 rats were grouped
      into five groups, each having 6 animals. Vehicle, sodium valproate (400 mg/kg)
      and ellagic acid (10, 25, 50 mg/kg) were given orally from day 1 to day 7, and
      ellagic acid was continued for 3 more days. On day fourteen, animals were
      sacrificed and the different parameters were recorded. There was a significant
      decrease in the sperm count and sperm motility after the exposure to sodium
      valproate. The percentage of abnormal sperms increased in a dose-dependent
      manner. The histopathological examination revealed that sodium valproate had
      caused degeneration and desquamation of germinal cells in the epithelium and also
      showed a decrease in the Johnsen's scoring. Ellagic acid provided partial
      protection at the doses of 10 and 25 mg/kg and complete protection at 50 mg/kg,
      against sodium valproate induced testicular and spermatozoal damage.

PMID- 26215012
TI  - Modification of mercury-induced biochemical alterations by Triticum Aestivum Linn
      in rats.
AB  - The present investigation has been undertaken to evaluate role of Wheat grass
      extract in modifying mercury-induced biochemical alterations in albino rats.
      Mercuric chloride 5 mg/kg body weight i.p. was given on 11, 13 & 15th day of the
      experiment. Wheat grass extract (400 mg/kg) and Quercetin (10 mg/kg) were
      administered 10 days before mercuric chloride administration and continued up to
      30 days after mercuric chloride administration. The animals were sacrificed on 1,
      15 and 30 days, the activity of serum alkaline and acid phosphatase and the iron,
      calcium, BUN, creatinine, SGPT, SGOT, total bilirubin, total protein levels were
      measured. Tissue lipid peroxidation content, glutathione (GSH) level, anti
      oxidant enzymes- CAT and GR were measured. Hematological indices were also
      estimated. Mercury intoxication causes significant increase (P < 0.001) in
      calcium level, acid phosphatase, BUN, creatinine, SGOT, SGPT, total bilirubin,
      lipid peroxidation content and significant decrease in iron level, alkaline
      phosphatase, total protein, and CAT, GR and glutathione level. Wheat grass
      extract pre- and post-treatment ameliorated mercury-induced alterations in terms
      of biochemical and hematological parameters. Concomitant treatment of Wheatgrass
      extract with Mercury showed prominent recovery and normal architecture with mild
      residual degeneration in the tissues. Thus from present investigation, it can be
      concluded that Wheat grass extract pre- and post-treatment with HgCl2
      significantly modulate or modify mercury-induced biochemical alteration in albino
      rats.

PMID- 26215013
TI  - Assessment of auditory evoked potential in long-term mobile phone users.
AB  - Mobile phones emit strong electromagnetic wave which causes structural and
      functional changes in the cell membrane within the central nervous system
      especially auditory system. The effect of duration of mobile phone use on
      auditory function was examined One hundred and seventy three long-term mobile
      phone users aged around 17-39 yrs (both male and female) were recruited in this
      study. The subjects were divided into three groups according to their age Group I
      (17-19 yrs), Group II (20-29 yrs), Group III (30-39 yrs). After getting informed
      consent the subjects were instructed to fill the questionnaire for the history
      related to our study, conduction deafness auditory brainstem response in both the
      ears were assessed. Significant difference was observed among three groups in
      their duration of mobile phone use. Latency of Waves in three groups showed
      significant difference. The average latency (both right and left ear) of waves I
      V was found to be prolonged in Group II when compared to Group I and Group III.
      Interpeak latencies I-V and I-III showed differences among three groups. The
      findings of present study showed abnormalities in the conduction of electrical
      signals in different levels of auditory pathway.

PMID- 26215015
TI  - Volunteerism: Is It Still Alive and Well?

PMID- 26215014
TI  - Polyphenol extract of ichnocarpus frutescens leaves modifies hyperglycemia in
      dexamethasone (dex) treated rats.
AB  - INTRODUCTION: The leaves of Ichnocarpus frutescens are used extensively as a
      decoction for the treatment of diabetes mellitus by the tribals of Karnataka and
      Uttar Pradesh states. METHODS: Anti-diabetic activity of polyphenol extract of
      Ichnocarpus frutescens was investigated using dexamethasone (DEX) induced
      hyperglycemia in Wistar rats. Experimental animals were injected subcutaneously
      with dexamethasone 3 mg/kg/day. After one week, hyperglycemic rats were orally
      treated with polyphenol extract (PPE) extracts at the dose of 300 mg/kg/day and
      150 mg/kg/day for a period of 14 days. RESULTS: Administration of DEX to fasted
      rats for 21 days resulted in insulin resistance evidenced by the significant
      increase in mean fasting blood glucose level (162.33 +/- 4.72 mg/dl). Both 300
      mg/kg and 150 mg/kg of PPE markedly reversed DEX induced mean fasting blood
      glucose level to 104.00 +/- 3.30 mg/dl and 145.5 +/- 1.99 mg/dl, respectively
      when compared with the positive control (p < 0.01). CONCLUSION: The possible
      mechanism by which polyphenol extract of I. frutescens brings about its
      antihyperglycemic action might be through potentiation of insulin sensitivity
      enhanced transport of blood glucose to the peripheral tissues. However, these
      findings suggest that polyphenol extract of I. frutescens therapy may reduce the
      risk of dexamethasone induced hyperglycemia in Wistar rats. These observations
      suggest that I. frutescens is a potential glucose lowering agent to ameliorate
      glucocorticoids induced hyperglycemia.

PMID- 26215016
TI  - Antibiotic Regimens--Full or Partial?

PMID- 26215017
TI  - Dentists Employed as Independent Contractors.

PMID- 26215018
TI  - Who Owns the Practice?

PMID- 26215019
TI  - Oral Pathology Quiz #86 Case Number 1.Unicystic ameloblastoma.

PMID- 26215020
TI  - Oral Pathology Quiz #86. Case Number 2. Proliferative verrucous leukoplakia.

PMID- 26215021
TI  - Oral Pathology Quiz #86. Case Number 3. Pyogenic granuloma.

PMID- 26215022
TI  - Oral Pathology Quiz #86. Case Number 4. Peripheral ossifying fibroma.

PMID- 26215023
TI  - Bruxism--Are You Helping or Hurting Your Patients?

PMID- 26215028
TI  - Dental Injuries and PIP: A Primer.

PMID- 26215029
TI  - Case Report--Fabrication Of Hinged Sectional Dentures In Restricted Mouth Opening
      Patients.

PMID- 26215031
TI  - Influence of Using Clinical Microscope as Auxiliary to Perform Mechanical
      Cleaning of Post Space: A Bond Strength Analysis.
AB  - INTRODUCTION: The aim of the present study was to evaluate the influence of using
      a clinical microscope while performing mechanical cleaning of post space walls on
      the bond strength of a fiberglass post to dentin. METHODS: Forty-five bovine
      roots were used. After preparation, roots were filled using gutta-percha and Pulp
      Canal Sealer (SybronEndo, Orange, CA). Subsequently, for post space preparation,
      the roots were divided into 3 groups: control (only heat condenser + specific bur
      of the post system); cleaning without a microscope, mechanical cleaning (after
      the procedure described in the control group, round burs were used to improve
      cleaning); and cleaning with a microscope, mechanical cleaning performed with
      round burs visualized under a clinical microscope. Then, fiberglass posts were
      cemented. The roots were prepared and evaluated by the push-out test. Data were
      analyzed using Kruskal-Wallis and Student-Newman-Keuls tests (P < .05). The
      failure pattern was classified as follows: adhesive between the cement and
      dentin, adhesive dentin/cement/post, mixed cohesive within dentin, mixed cohesive
      post, and mixed cohesive post/dentin. RESULTS: The bond strength values (mean +/-
      standard deviation) were control (cervical 1.17 +/- 1.1, middle 0.40 +/- 0.3,
      apical 0.52 +/- 0.3, and total 0.95 +/- 1.9), cleaning without a microscope
      (cervical 1.66 +/- 2.3, middle 0.65 +/- 1.1, apical 0.79 +/- 1.2, and total1.04
      +/- 1.7), and cleaning with a microscope (cervical 3.26 +/- 2.8, middle 1.97 +/-
      3.5, apical 1.85 +/- 4.1, and total 2.37 +/- 3.5). In the cleaning with a
      microscope group, the bond strength values were significantly higher than those
      in the other groups. In all groups, the main failure pattern was adhesive between
      cement and dentin. CONCLUSIONS: The use of a clinical microscope while performing
      mechanical cleaning during post space preparation improved the bond strength of a
      fiberglass post to dentin.

PMID- 26215030
TI  - Rapid parallel measurements of macroautophagy and mitophagy in mammalian cells
      using a single fluorescent biosensor.
AB  - Mitochondrial dysfunction is implicated in many human diseases and occurs in
      normal aging. Mitochondrial health is maintained through organelle biogenesis and
      repair or turnover of existing mitochondria. Mitochondrial turnover is
      principally mediated by mitophagy, the trafficking of damaged mitochondria to
      lysosomes via macroautophagy (autophagy). Mitophagy requires autophagy, but is
      itself a selective process that relies on specific autophagy-targeting
      mechanisms, and thus can be dissociated from autophagy under certain
      circumstances. Therefore, it is important to assess autophagy and mitophagy
      together and separately. We sought to develop a robust, high-throughput,
      quantitative method for monitoring both processes in parallel. Here we report a
      flow cytometry-based assay capable of rapid parallel measurements of mitophagy
      and autophagy in mammalian cells using a single fluorescent protein biosensor. We
      demonstrate the ability of the assay to quantify Parkin-dependent selective
      mitophagy in CCCP-treated HeLa cells. In addition, we show the utility of the
      assay for measuring mitophagy in other cell lines, as well as for Parkin
      independent mitophagy stimulated by deferiprone. The assay makes rapid
      measurements (10,000 cells per 6 seconds) and can be combined with other
      fluorescent indicators to monitor distinct cell populations, enabling design of
      high-throughput screening experiments to identify novel regulators of mitophagy
      in mammalian cells.

PMID- 26215032
TI  - Temporal trends in the incidence and relative survival of non-small cell lung
      cancer in Canada: A population-based study.
AB  - OBJECTIVES: The objective of this study was to estimate trends in incidence and
      relative survival ratio in patients diagnosed with invasive lung cancer in Canada
      over the period of 1992-2007. MATERIALS AND METHODS: We identified patients with
      primary invasive non-small cell lung cancers in the Canadian Cancer Registry
      (CCR) dataset. Patients younger than 18 years of age were excluded in this
      analysis. A flexible parametric model was used to estimate one- and five-year
      relative survival ratios and excess mortality rate. RESULTS: In total 182,417,
      patients from CCR dataset with invasive lung cancer were identified of which
      57.2% (n=106,197) were male and the mean age at diagnosis was 68.8 (SD=11.0)
      years. The incidence rate of lung cancer decreased in men and increased in women.
      Although one-year relative survival ratio slightly improved over time for both
      genders and most age groups, five-year relative survival decreased for most of
      the groups. CONCLUSIONS: Although the incidence rate of invasive lung cancer
      continued to decrease in men, it is increasing in women and the gap in incidence
      between men and women is narrowing. The one-year relative survival ratio
      gradually increased for most age groups over the study period, particularly for
      the younger age groups. Additionally, excess mortality rate is at its peak
      shortly after diagnosis and for the first 6 months and thereafter gradually
      decreases.

PMID- 26215034
TI  - Immunogenetics of rheumatoid arthritis: Understanding functional implications.
AB  - The last decade has seen a dramatic technological revolution. The
      characterisation of the majority of the common variations in our genetic code in
      2003 precipitated the discovery of the genetic risk factors predisposing to
      Rheumatoid Arthritis development and progression. Prior to 2007, only a handful
      of genetic risk factors had been identified, HLA, PTPN22 and CTLA4. Since then,
      over 100 genetic risk loci have been described, with the prediction that an ever
      increasing number of risk alleles with consistently decreasing effect sizes will
      be discovered in the years to come. Each risk locus harbours multiple candidate
      genes and the proof of causality of each of these candidates is as yet unknown.
      An enrichment of these RA-associated genes is found in three pathways: T-cell
      receptor signalling, JAK-STAT signalling and the NF-kappaB signalling cascade,
      and currently drugs targeting these pathways are available for the treatment of
      RA. However, the role that RA-associated genes have in these pathways and how
      they contribute to disease is not always clear. Major efforts in understanding
      the contribution of genetic risk factors are currently under way with studies
      querying the role of genetic variation in gene expression of coding and non
      coding genes, epigenetic marks and other regulatory mechanisms yielding ever more
      valuable insights into mechanisms of disease. Recent work has suggested a
      possible enrichment of non-coding RNAs as well as super-enhancers in RA genetic
      loci indicating possible new insights into disease mechanism. This review brings
      together these emerging genetic data with an emphasis on the immunogenetic links
      these findings have provided and what we expect the future will bring.

PMID- 26215033
TI  - The immunogenetics of Psoriasis: A comprehensive review.
AB  - Psoriasis vulgaris is a common, chronic inflammatory skin disease with a complex
      etiology involving genetic risk factors and environmental triggers. Here we
      describe the many known genetic predispositions of psoriasis with respect to
      immune genes and their encoded pathways in psoriasis susceptibility. These genes
      span an array of functions that involve antigen presentation (HLA-Cw6, ERAP1,
      ERAP2, MICA), the IL-23 axis (IL12Bp40, IL23Ap19, IL23R, JAK2, TYK2), T-cell
      development and T-cells polarization (RUNX1, RUNX3, STAT3, TAGAP, IL4, IL13),
      innate immunity (CARD14, c-REL, TRAF3IP2, DDX58, IFIH1), and negative regulators
      of immune responses (TNIP1, TNFAIP3, NFKBIA, ZC3H12C, IL36RN, SOCS1). The
      contribution of some of these gene products to psoriatic disease has also been
      revealed in recent years through targeting of key immune components, such as the
      Th17/IL-23 axis which has been highly successful in disease treatment. However,
      many of the genetic findings involve immune genes with less clear roles in
      psoriasis pathogenesis. This is particularly the case for those genes involved in
      innate immunity and negative regulation of immune specific pathways. It is
      possible that risk alleles of these genes decrease the threshold for the initial
      activation of the innate immune response. This could then lead to the onslaught
      of the pathogenic adaptive immune response known to be active in psoriatic skin.
      However, precisely how these various genes affect immunobiology need to be
      determined and some are speculated upon in this review. These novel genetic
      findings also open opportunities to explore novel therapeutic targets and
      potentially the development of personalized medicine, as well as discover new
      biology of human skin disease.

PMID- 26215035
TI  - Propensity score interval matching: using bootstrap confidence intervals for
      accommodating estimation errors of propensity scores.
AB  - BACKGROUND: Propensity score methods have become a popular tool for reducing
      selection bias in making causal inference from observational studies in medical
      research. Propensity score matching, a key component of propensity score methods,
      normally matches units based on the distance between point estimates of the
      propensity scores. The problem with this technique is that it is difficult to
      establish a sensible criterion to evaluate the closeness of matched units without
      knowing estimation errors of the propensity scores. METHODS: The present study
      introduces interval matching using bootstrap confidence intervals for
      accommodating estimation errors of propensity scores. In interval matching, if
      the confidence interval of a unit in the treatment group overlaps with that of
      one or more units in the comparison group, they are considered as matched units.
      RESULTS: The procedure of interval matching is illustrated in an empirical
      example using a real-life dataset from the Nursing Home Compare, a national
      survey conducted by the Centers for Medicare and Medicaid Services. The empirical
      example provided promising evidence that interval matching reduced more selection
      bias than did commonly used matching methods including the rival method, caliper
      matching. Interval matching's approach methodologically sounds more meaningful
      than its competing matching methods because interval matching develop a more
      "scientific" criterion for matching units using confidence intervals.
      CONCLUSIONS: Interval matching is a promisingly better alternative tool for
      reducing selection bias in making causal inference from observational studies,
      especially useful in secondary data analysis on national databases such as the
      Centers for Medicare and Medicaid Services data.

PMID- 26215036
TI  - Blockade of bone morphogenetic protein signaling potentiates the pro-inflammatory
      phenotype induced by interleukin-17 and tumor necrosis factor-alpha combination
      in rheumatoid synoviocytes.
AB  - INTRODUCTION: Bone morphogenetic proteins (BMPs) are multifunctional secreted
      growth factors regulating a broad spectrum of functions in numerous systems. An
      increased expression and production of specific BMPs have been described in the
      rheumatoid arthritis (RA) synovium. The aim of this study was to analyze the
      involvement of the BMP signaling pathway in RA synoviocytes in response to
      interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-alpha). METHODS: The
      expression of components of the BMP signaling pathway (BMP receptors, BMP
      ligands, BMP signal transducers, and BMP antagonists) was analyzed by
      quantitative polymerase chain reaction before and after treatment of RA
      synoviocytes with TNF-alpha or IL-17 or both. Regulation was studied in the
      presence of the specific BMP inhibitor DMH1 (dorsomorphin homologue 1) or an
      exogenous BMP ligand, BMP6. Expression and production of pro-inflammatory
      cytokines (IL-6 and granulocyte-macrophage colony-stimulating factor), chemokines
      (IL-8, CCL2, CCL5, and CXCL10), and matrix metalloproteinases (MMP-1, -2, -3, -9,
      and -13) were analyzed. RESULTS: RA synoviocytes express BMP receptors (mainly
      BMPRIA, ACTRIA, and BMPRII), signal transducers of the Smad family (Smad1 and 5
      and co-Smad4), and different BMP antagonists. The modulation of the expression of
      the BMP target genes-Id (inhibitor of DNA-binding/differentiation) proteins and
      Runx (Runt-related transcription factor) transcription factors-after the addition
      of exogenous BMP shows that the BMP signaling pathway is active. RA synoviocytes
      also express BMP ligands (BMP2, BMP6, and BMP7) which are highly upregulated
      after activation with TNF-alpha and IL-17. Autocrine BMP signaling pathway can be
      blocked by treatment with the inhibitor DMH1, leading to an increase in the
      upregulated expression of pro-inflammatory cytokines, chemokines, and MMPs
      induced by the activation of RA synoviocytes with TNF-alpha and IL-17.
      Conversely, the additional stimulation of the BMP pathway with the exogenous
      addition of the BMP6 ligand decreases the expression of those pro-inflammatory
      and pro-destructive factors. CONCLUSION: The results indicate that the canonical
      BMP pathway is functionally active in human RA synoviocytes and that the
      inhibition of autocrine BMP signaling exacerbates the pro-inflammatory phenotype
      induced in RA synoviocytes by the stimulation with IL-17 and TNF-alpha.

PMID- 26215037
TI  - Increased SHP-1 expression results in radioresistance, inhibition of cellular
      senescence, and cell cycle redistribution in nasopharyngeal carcinoma cells.
AB  - BACKGROUND: Radioresistance is the main limit to the efficacy of radiotherapy in
      nasopharyngeal carcinoma (NPC). SHP-1 is involved in cancer progression, but its
      role in radioresistance and senescence of NPC is not well understood. This study
      aimed to assess the role of SHP-1 in the radioresistance and senescence of NPC
      cells. METHODS: SHP-1 was knocked-down and overexpressed in CNE-1 and CNE-2 cells
      using lentiviruses. Cells were irradiated to observe their radiosensitivity by
      colony forming assay. BrdU incorporation assay and flow cytometry were used to
      monitor cell cycle. A beta-galactosidase assay was used to assess senescence.
      Western blot was used to assess SHP-1, p21, p53, pRb, Rb, H3K9Me3, HP1gamma,
      CDK4, cyclin D1, cyclin E, and p16 protein expressions. RESULTS: Compared with
      CNE-1-scramble shRNA cells, SHP-1 downregulation resulted in increased senescence
      (+107%, P < 0.001), increased radiosensitivity, higher proportion of cells in
      G0/G1 (+33%, P < 0.001), decreased expressions of CDK4 (-44%, P < 0.001), cyclin
      D1 (-41%, P = 0.001), cyclin E (-97%, P < 0.001), Rb (-79%, P < 0.001), and pRb (
      76%, P = 0.001), and increased expression of p16 (+120%, P = 0.02). Furthermore,
      SHP-1 overexpression resulted in radioresistance, inhibition of cellular
      senescence, and cell cycle arrest in the S phase. Levels of p53 and p21 were
      unchanged in both cell lines (all P > 0.05). CONCLUSION: SHP-1 has a critical
      role in radioresistance, cell cycle progression, and senescence of NPC cells.
      Down-regulating SHP-1 may be a promising therapeutic approach for treating
      patients with NPC.

PMID- 26215038
TI  - The Psychological Inflexibility in Pain Scale (PIPS) - validation, factor
      structure and comparison to the Chronic Pain Acceptance Questionnaire (CPAQ) and
      other validated measures in German chronic back pain patients.
AB  - BACKGROUND: Acceptance and Commitment Therapy (ACT) for pain offers an
      alternative to traditional Cognitive Behavioural Therapy (CBT) approaches. ACT
      focuses on the enhancement of 'psychological flexibility' that enables
      individuals to pursue their values and goals despite pain. To assess specific
      treatment effect or mediators and moderators of change, questionnaires measuring
      ACT constructs are needed. METHODS: The Psychological Inflexibility in Pain Scale
      (PIPS) was translated into German and completed by 182 participants with chronic
      back pain (70.3 % women, age 51.0 +/- 10.5 years). Item analyses and a
      confirmatory factor analysis were computed as well as correlations with the
      Chronic Pain Acceptance Questionnaire (CPAQ), which measures related, but
      slightly different ACT-related constructs, and self-reported disability, pain
      intensity and further pain-related questionnaires. RESULTS: The confirmatory
      factor analysis reproduced the original structure with two subscales and a good
      fit. The internal consistencies of the subscales were Cronbach's alpha = .91
      (Avoidance) and alpha = .26 (Fusion). Average item-whole correlations of the
      items with the respective subscales were r = .71 (Avoidance) and r = .20
      (Fusion). The highest correlations were observed for Avoidance with the CPAQ (r =
      -.81), the Tampa Scale of Kinesiophobia (r = .58) and the Pain Catastrophizing
      Scale (r = .56) and for Fusion with the CPAQ subscale Pain willingness (r = 
      .55). The PIPS subscale Avoidance predicted pain-related disability even after
      controlling for catastrophizing and fear of movement. CONCLUSIONS: The PIPS
      subscale Avoidance may be a valuable instrument to assess treatment processes in
      future RCTs. The PIPS subscale Fusion seemed more problematic in the German
      sample with chronic back pain. More research on the comparison between PIPS and
      other questionnaires assessing psychological flexibility and the usefulness of
      the concept 'Fusion' for chronic pain are needed.

PMID- 26215039
TI  - The pain of a heart being broken: pain experience and use of analgesics by
      caregivers of patients with Alzheimer's disease.
AB  - BACKGROUND: It has been observed that psychical suffering (e.g. the feeling of
      losing a significant person) tends to reduce the physical pain tolerance
      threshold, as well as to increase the subjective sense of painfulness. The
      purpose of this study was to assess pain sensation among a group of caregivers of
      patients with Alzheimer's disease, and to determine the psychological factors
      (emotional and relational) that contribute to both pain perception and coping
      with pain via the use of analgesics. METHODS: The study comprised 127 caregivers
      of patients with Alzheimer's disease. Questionnaires were used to elicit pain
      intensity, strength of emotional relationship between caregiver and patient,
      sense of painfulness of the loss experienced, depression level, and somatic
      ailments. RESULTS: A large majority (87.4%) of participants reported pain
      complaints, while 93% took analgesics without a doctor's recommendation at least
      once a week; 8% took painkillers daily. The strongest predictors of both
      perceived pain and tendency to use analgesics were sense of loss and painfulness
      of loss in relation to the patient's deteriorating condition. CONCLUSIONS: The
      pain experienced by caregivers may be connected to social pain resulting from the
      experience of losing someone they are close to. Caregivers may resort to
      excessive use of analgesics as a pain-coping strategy.

PMID- 26215040
TI  - The complex remuneration of human resources for health in low-income settings:
      policy implications and a research agenda for designing effective financial
      incentives.
AB  - BACKGROUND: Human resources for health represent an essential component of health
      systems and play a key role to accelerate progress towards universal health
      coverage. Many countries in sub-Saharan Africa face challenges regarding the
      availability, distribution and performance of health workers, which could be in
      part addressed by providing effective financial incentives. METHODS: Based on an
      overview of the existing literature, the paper highlights the gaps in the
      existing research in low-income countries exploring the different components of
      health workers' incomes. It then proposes a novel approach to the analysis of
      financial incentives and delineates a research agenda, which could contribute to
      shed light on this topic. FINDINGS: The article finds that, while there is ample
      research that investigates separately each of the incomes health workers may earn
      (for example, salary, fee-for-service payments, informal incomes, "top-ups" and
      per diems, dual practice and non-health activities), there is a dearth of studies
      which look at the health workers' "complex remuneration", that is, the whole of
      the financial incentives available. Little research exists which analyses
      simultaneously all revenues of health workers, quantifies the overall
      remuneration and explores its complexity, its multiple components and their
      features, as well as the possible interaction between income components. However,
      such a comprehensive approach is essential to fully comprehend health workers'
      incentives, by investigating the causes (at individual and system level) of the
      fragmentation in the income structure and the variability in income levels, as
      well as the consequences of the "complex remuneration" on motivation and
      performance. This proposition has important policy implications in terms of
      devising effective incentive packages as it calls for an active consideration of
      the role that "complex remuneration" plays in determining recruitment, retention
      and motivation patterns, as well as, more broadly, the performance of health
      systems. CONCLUSIONS: This paper argues that research focusing on the health
      workers' "complex remuneration" is critical to address some of the most
      challenging issues affecting human resources for health. An empirical research
      agenda is proposed to fill the gap in our understanding.

PMID- 26215041
TI  - Phototropins maintain robust circadian oscillation of PSII operating efficiency
      under blue light.
AB  - The circadian system allows plants to coordinate metabolic and physiological
      functions with predictable environmental variables such as dusk and dawn. This
      endogenous oscillator is comprised of biochemical and transcriptional rhythms
      that are synchronized with a plant's surroundings via environmental signals,
      including light and temperature. We have used chlorophyll fluorescence techniques
      to describe circadian rhythms of PSII operating efficiency (Fq'/Fm') in the
      chloroplasts of Arabidopsis thaliana. These Fq'/Fm' oscillations appear to be
      influenced by transcriptional feedback loops previously described in the nucleus,
      and are induced by rhythmic changes in photochemical quenching over circadian
      time. Our work reveals that a family of blue photoreceptors, phototropins,
      maintain robust rhythms of Fq'/Fm' under constant blue light. As phototropins do
      not influence circadian gene expression in the nucleus our imaging methodology
      highlights differences between the modulation of circadian outputs in distinct
      subcellular compartments. 

PMID- 26215042
TI  - Effect of a topical anaesthetic formulation on the cortisol response to surgical
      castration of unweaned beef calves.
AB  - Impracticality and cost of existing pain management strategies during surgical
      castration of beef cattle have limited their widespread implementation on-farm. A
      farmer-applied topical anaesthetic formulation, originally developed and used
      commercially to mitigate the pain of mulesing in lambs, was investigated for its
      potential use for managing pain in surgically castrated calves. This formulation
      contained lidocaine, bupivacaine, adrenalin and cetrimide. In this study, 24
      Angus bull calves were randomly allocated to (1) surgical castration (C, n=8),
      (2) surgical castration with the post-operative application of topical
      anaesthetic (CTA, n=8) and (3) sham castration/control (CON, n=8). The experiment
      was conducted over 2 days, with treatment groups evenly represented across each
      day. Calves were habituated to handling before the experiment and blood samples
      were collected for plasma cortisol measurement at defined time periods before, at
      and post treatment, (at -0.5, 0 h, then +0.5, 1, 1.5, 2, 4 and 6 h). There was a
      significant effect of time on cortisol concentrations across all treatment groups
      (P<0.01), with lowest concentrations at -0.5 and 6 h and peak concentration at
      0.5 h being significantly higher than the cortisol response at 0 h. The effect of
      treatment was not significant (P=0.077), however, there was a trend for CON
      calves to display lower cortisol concentrations than C and CTA calves and CTA
      calves to display lower cortisol concentrations than C calves. The mean area
      under the curve (AUC) of CON calves was significantly lower than those of C and
      CTA calves (P=0.04), however, there was no significant difference between the
      AUCs of CTA and C calves. Immediate application of topical anaesthetic after
      surgical castration did not significantly reduce plasma cortisol concentrations.
      However, the trend for CTA calves to display lower cortisol concentrations than C
      calves warrants further investigation into the use of TA for pain relief of
      surgically castrated beef calves. 

PMID- 26215043
TI  - Clinical trials: subgroup analyses in randomized trials--more rigour needed.

PMID- 26215045
TI  - Urological cancer: management of patients with prostate cancer: evolution towards
      a risk-stratified approach.

PMID- 26215044
TI  - First-line chemotherapy for mCRC-a review and evidence-based algorithm.
AB  - The response to first-line therapy is a primary determinant of outcome in
      patients with metastatic colorectal cancer (mCRC), for three main reasons:
      effective upfront therapy provides a unique opportunity to cure some patients;
      can be crucial in delaying disease progression and achieving symptom relief; and
      can improve patient eligibility for, and the effectiveness of, further
      treatments. In the past decade, decision-making regarding the choice of first
      line therapy for mCRC has been complicated by the availability of many different
      options without a definitive consensus on a specific standard of care (despite
      major advances in categorizing predictive molecular disease subtypes). Most of
      the efforts of the scientific community have been directed at establishing the
      best biologic agent to be combined with a chemotherapy doublet, although a
      different branch of research has produced new data that underscore the importance
      of defining the optimal chemotherapy backbone. Herein, we review the key clinical
      trials completed in the past 10 years that have investigated and compared the use
      of chemotherapy doublets, triplets, and monotherapies, with or without
      molecularly targeted biologic agents, in the first-line treatment of patients
      with mCRC. Our examination of the literature led us to propose a new patient
      oriented algorithm to guide clinicians' decisions on the best choice of upfront
      therapy for mCRC. 

PMID- 26215046
TI  - Splenogonadal fusion: a rare scrotal mass in a 9-year-old boy.

PMID- 26215047
TI  - Investigation into the mechanism of action of the antimicrobial peptides Os and
      Os-C derived from a tick defensin.
AB  - Os and Os-C are two novel antimicrobial peptides, derived from a tick defensin,
      which have been shown to have a larger range of antimicrobial activity than the
      parent peptide, OsDef2. The aim of this study was to determine whether the
      peptides Os and Os-C are mainly membrane acting, or if these peptides have
      possible additional intracellular targets in Escherichia coli and Bacillus
      subtilis. Transmission electron microscopy revealed that both peptides adversely
      affected intracellular structure of both bacteria causing different degrees of
      granulation of the intracellular contents. At the minimum bactericidal
      concentrations, permeabilization as determined with the SYTOX green assay seemed
      not to be the principle mode of killing when compared to melittin. However,
      fluorescent triple staining indicated that the peptides caused permeabilization
      of stationary phase bacteria and TEM indicated membrane effects. Studies using
      fluorescently labeled peptides revealed that the membrane penetrating activity of
      Os and Os-C was similar to buforin II. Os-C was found to associate with the septa
      of B. subtilis. Plasmid binding studies showed that Os and Os-C binds E. coli
      plasmid DNA at a similar charge ratio as melittin. These studies suggest membrane
      activity for Os and Os-C with possible intracellular targets such as DNA. The
      differences in permeabilization at lower concentrations and binding to DNA
      between Os and Os-C, suggest that the two peptides have dissimilar modes of
      action. 

PMID- 26215049
TI  - The cost of training.

PMID- 26215048
TI  - Signalling pathways involved in the detection of peptones by murine small
      intestinal enteroendocrine L-cells.
AB  - Glucagon like peptide-1 is an insulinotropic hormone released from intestinal L
      cells in response to food ingestion. Here, we investigated mechanisms underlying
      the sensing of peptones by primary small intestinal L-cells. Meat, casein and
      vegetable-derived peptones (5 mg/ml), the L-amino acids Phe, Trp, Gln and Ala (20
      mM each), and the dipeptide glycine-sarcosine (20 mM) stimulated GLP-1 secretion
      from primary cultures prepared from the small intestine. Further mechanistic
      studies were performed with meat peptone, and revealed the elevation of
      intracellular calcium in L-cells. Inhibition of the calcium sensing receptor
      (CaSR), transient receptor potential (TRP) channels and Q-type voltage gated
      calcium channels (VGCC) significantly attenuated peptone-stimulated GLP-1 release
      and reduced intracellular Ca(2+) responses. CaSR inhibition also attenuated the
      GLP-1 secretory response to Gln. Targeting these pathways in L-cells could be
      used to increase endogenous production of GLP-1 and offer exploitable avenues for
      the development of therapeutics to treat diabetes and obesity. 

PMID- 26215050
TI  - Genomic analyses of pneumococci reveal a wide diversity of bacteriocins -
      including pneumocyclicin, a novel circular bacteriocin.
AB  - BACKGROUND: One of the most important global pathogens infecting all age groups
      is Streptococcus pneumoniae (the 'pneumococcus'). Pneumococci reside in the
      paediatric nasopharynx, where they compete for space and resources, and one
      competition strategy is to produce a bacteriocin (antimicrobial peptide or
      protein) to attack other bacteria and an immunity protein to protect against self
      destruction. We analysed a collection of 336 diverse pneumococcal genomes dating
      from 1916 onwards, identified bacteriocin cassettes, detailed their genetic
      composition and sequence diversity, and evaluated the data in the context of the
      pneumococcal population structure. RESULTS: We found that all genomes maintained
      a blp bacteriocin cassette and we identified several novel blp cassettes and
      genes. The composition of the 'bacteriocin/immunity region' of the blp cassette
      was highly variable: one cassette possessed six bacteriocin genes and eight
      putative immunity genes, whereas another cassette had only one of each. Both
      widely-distributed and highly clonal blp cassettes were identified. Most
      surprisingly, one-third of pneumococcal genomes also possessed a cassette
      encoding a novel circular bacteriocin that we called pneumocyclicin, which shared
      a similar genetic organisation to well-characterised circular bacteriocin
      cassettes in other bacterial species. Pneumocyclicin cassettes were mainly of one
      genetic cluster and largely found among seven major pneumococcal clonal
      complexes. CONCLUSIONS: These detailed genomic analyses revealed a novel
      pneumocyclicin cassette and a wide variety of blp bacteriocin cassettes,
      suggesting that competition in the nasopharynx is a complex biological
      phenomenon.

PMID- 26215051
TI  - Asteroid Risk Assessment: A Probabilistic Approach.
AB  - Following the 2013 Chelyabinsk event, the risks posed by asteroids attracted
      renewed interest, from both the scientific and policy-making communities. It
      reminded the world that impacts from near-Earth objects (NEOs), while rare, have
      the potential to cause great damage to cities and populations. Point estimates of
      the risk (such as mean numbers of casualties) have been proposed, but because of
      the low-probability, high-consequence nature of asteroid impacts, these averages
      provide limited actionable information. While more work is needed to further
      refine its input distributions (e.g., NEO diameters), the probabilistic model
      presented in this article allows a more complete evaluation of the risk of NEO
      impacts because the results are distributions that cover the range of potential
      casualties. This model is based on a modularized simulation that uses
      probabilistic inputs to estimate probabilistic risk metrics, including those of
      rare asteroid impacts. Illustrative results of this analysis are presented for a
      period of 100 years. As part of this demonstration, we assess the effectiveness
      of civil defense measures in mitigating the risk of human casualties. We find
      that they are likely to be beneficial but not a panacea. We also compute the
      probability-but not the consequences-of an impact with global effects
      ("cataclysm"). We conclude that there is a continued need for NEO observation,
      and for analyses of the feasibility and risk-reduction effectiveness of space
      missions designed to deflect or destroy asteroids that threaten the Earth. 

PMID- 26215052
TI  - Does azithromycin modify viral load during severe respiratory syncytial virus
      bronchiolitis?

PMID- 26215053
TI  - Gas1 Knockdown Increases the Neuroprotective Effect of Glial Cell-Derived
      Neurotrophic Factor Against Glutamate-Induced Cell Injury in Human SH-SY5Y
      Neuroblastoma Cells.
AB  - Growth arrest-specific 1 (Gas1) protein acts as an inhibitor of cell growth and a
      mediator of cell death in nervous system during development and is also re
      expressed in adult neurons during excitotoxic insult. Due to its structural
      similarity to the glial cell-derived neurotrophic factor family receptors alpha
      (GFRalpha), Gas1 is likely to interfere with the neuroprotective effect of GDNF.
      In the present study, we investigated the expression profile of Gas1 during
      glutamate insults in human SH-SY5Y neuroblastoma cells as well as the influence
      of Gas1 inhibition on the protective effect of GDNF against glutamate-induced
      cell injury. Our data showed that Gas1 expression was significantly increased
      with the treatment of glutamate in SH-SY5Y cells. The silencing of Gas1 by small
      interfering RNA promoted the protective effect of GDNF against glutamate-induced
      cytotoxicity as well as cell apoptosis, which effect was likely mediated through
      activating Akt/PI3 K-dependent cell survival signaling pathway and inhibiting
      mitochondrial-dependent cell apoptosis signaling pathway via Bad
      dephosphorylation blockade. In summary, this study showed the synergistic effect
      of Gas1 inhibition and GDNF against glutamate-induced cell injury in human SH
      SY5Y neuroblastoma cells, which information might significantly contribute to
      better understanding the function of Gas1 in neuronal cells and form the basis of
      the therapeutic development of GDNF in treating human neurodegenerative diseases
      in the future. 

PMID- 26215054
TI  - Gastro-protective and Anti-stress Efficacies of Monomethyl Fumarate and a Fumaria
      indica Extract in Chronically Stressed Rats.
AB  - Results of the very first experiments conducted to evaluate therapeutic
      potentials of a fumarate containing Fumaria indica extract and of fairly low
      daily oral doses of monomethyl fumarate for prevention of chronic unavoidable
      foot-shock stress-induced gastric ulcers, and possible involvement of diverse
      neuro-hormonal and oxidative process in their stress response desensitizing
      effects are reported and discussed in this article. Preventive effects of 21
      daily oral 60, 120, and 240 mg/kg doses of a standardized 50 % methanolic F.
      indica extract (MFI) and 1.25, 2.50, and 5.00 mg/kg/day of pure monomethyl
      fumarate (MMF) were compared in rats subjected to one hour daily unavoidable foot
      shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract
      was used as a reference herbal anti-stress agent in all experiments. Effects of
      the treatments on stress-induced alterations in body weight, adrenal and spleen
      weights, gastric ulcer and ulcer index, weight of glandular stomach, protective
      mucosal glycoprotein content, cellular proliferation, oxidative stress on stomach
      fundus, and brain tissues of male rats were quantified. Other parameters
      quantified were plasma corticosterone levels, brain monoamine levels, and
      expressions of the cytokines TNF-alpha, IL-10, and IL-1beta in blood and brain of
      stressed and treated rats. Most but not every observed stress-induced anomalies
      were suppressed or completely prevented by both MFI and pure MMF treatments in
      dose-dependent manner. Qualitatively, the observed activity profiles of both of
      them were similar to those of WS dose tested. These results reveal that both MFI
      and MMF are potent gastro-protective agents against chronic unavoidable stress
      induced ulcers and strongly suggest that they act as regulators or modulators of
      monoamine, corticosterone, and cytokine homeostasis. 

PMID- 26215056
TI  - StARTing to understand membrane contact sites.
AB  - Lipid transport proteins localized to membrane contact sites mediate the
      distribution of lipids between organelles. Recently identified StART-like sterol
      transporting proteins in yeast can explain sterol delivery within the cell. The
      multiple localizations of these proteins could provide alternative routes for
      sterol delivery and mediate inter-regulation of membrane contact sites. 

PMID- 26215055
TI  - Recognition- and reactivity-based fluorescent probes for studying transition
      metal signaling in living systems.
AB  - Metals are essential for life, playing critical roles in all aspects of the
      central dogma of biology (e.g., the transcription and translation of nucleic
      acids and synthesis of proteins). Redox-inactive alkali, alkaline earth, and
      transition metals such as sodium, potassium, calcium, and zinc are widely
      recognized as dynamic signals, whereas redox-active transition metals such as
      copper and iron are traditionally thought of as sequestered by protein ligands,
      including as static enzyme cofactors, in part because of their potential to
      trigger oxidative stress and damage via Fenton chemistry. Metals in biology can
      be broadly categorized into two pools: static and labile. In the former, proteins
      and other macromolecules tightly bind metals; in the latter, metals are bound
      relatively weakly to cellular ligands, including proteins and low molecular
      weight ligands. Fluorescent probes can be useful tools for studying the roles of
      transition metals in their labile forms. Probes for imaging transition metal
      dynamics in living systems must meet several stringent criteria. In addition to
      exhibiting desirable photophysical properties and biocompatibility, they must be
      selective and show a fluorescence turn-on response to the metal of interest. To
      meet this challenge, we have pursued two general strategies for metal detection,
      termed "recognition" and "reactivity". Our design of transition metal probes
      makes use of a recognition-based approach for copper and nickel and a reactivity
      based approach for cobalt and iron. This Account summarizes progress in our
      laboratory on both the development and application of fluorescent probes to
      identify and study the signaling roles of transition metals in biology. In
      conjunction with complementary methods for direct metal detection and genetic
      and/or pharmacological manipulations, fluorescent probes for transition metals
      have helped reveal a number of principles underlying transition metal dynamics.
      In this Account, we give three recent examples from our laboratory and
      collaborations in which applications of chemical probes reveal that labile copper
      contributes to various physiologies. The first example shows that copper is an
      endogenous regulator of neuronal activity, the second illustrates cellular
      prioritization of mitochondrial copper homeostasis, and the third identifies the
      "cuprosome" as a new copper storage compartment in Chlamydomonas reinhardtii
      green algae. Indeed, recognition- and reactivity-based fluorescent probes have
      helped to uncover new biological roles for labile transition metals, and the
      further development of fluorescent probes, including ones with varied Kd values
      and new reaction triggers and recognition receptors, will continue to reveal
      exciting and new biological roles for labile transition metals. 

PMID- 26215057
TI  - Galectin-11: A novel host mediator targeting specific stages of the
      gastrointestinal nematode parasite, Haemonchus contortus.
AB  - Galectin-11 is released from epithelial cells of the gastrointestinal tract,
      specifically following infection with gastrointestinal parasites including the
      highly pathogenic nematode, Haemonchus contortus. The function(s) of galectin-11
      are currently unknown but seem to be associated with the development of immunity
      by the host. The aim of the present study was to examine the interaction of
      galectin-11 with the different parasitic life cycle stages of H. contortus and
      determine any effects on parasite development. The results of this study showed
      that galectin-11 binds to the surface of the L4 and adult stages of the parasite
      but not to the exsheathed L3 stage. In addition, at a lower concentration,
      binding to the L4 was specifically localised to the pharynx region. Subsequent in
      vitro assays demonstrated significant inhibition of larval growth and development
      in the presence of recombinant galectin-11. These results indicate, to our
      knowledge for the first time, a functional role for galectin-11 in
      gastrointestinal nematode infection of ruminants and a mechanism of action of
      galectin-11, targeting the development and growth of the L4 and possibly the
      adult parasite stage. 

PMID- 26215059
TI  - Clinical and genetic analysis of pediatric patients with Wilson disease.
AB  - BACKGROUND/AIMS: Wilson disease (WD, MIM# 277900) is an autosomal recessive
      disorder of copper transport resulting from the defective function of a copper
      transporting P-type ATPase. Detecting mutations and single nucleotide
      polymorphisms (SNPs) of the ATP7B gene in Turkish pediatric WD patients (n=32)
      and controls (n=52) is the aim of this research. MATERIALS AND METHODS: For
      screening mutations and SNPs of the ATP7B gene, sequencing was performed.
      RESULTS: Mutations were determined in the ATP7B gene in 23 out of the 32
      pediatric patients. The mutation detection rate in the ATP7B gene of the
      pediatric Turkish WD patients was 71.875%. Fifteen different mutations were
      determined in the ATP7B gene. These mutations were distributed throughout the
      ATP7B gene and were as follows: 2 deletion, 1 insertion, 3 nonsense, and 9
      missense mutations. Four of these, including c.3111delC (1 deletion) and
      c.2363C>T, c.3733C>A, and c.3451C>T (3 missense) mutations, were detected in the
      Turkish WD patients. Eleven polymorphisms were detected in both groups. Among
      these, c.3727G>A (SNP) was reported in the Wilson Disease Mutation Database by
      our group. Nine out of the thirty-two pediatric Turkish WD patients had no
      mutations in the ATP7B gene. CONCLUSION: To find the cause of WD in pediatric
      patients who have no mutation in ATP7B, additional research is necessary.

PMID- 26215058
TI  - Leishmania major UDP-sugar pyrophosphorylase salvages galactose for
      glycoconjugate biosynthesis.
AB  - Leishmaniases are a set of tropical and sub-tropical diseases caused by protozoan
      parasites of the genus Leishmania whose severity ranges from self-healing
      cutaneous lesions to fatal visceral infections. Leishmania parasites synthesise a
      wide array of cell surface and secreted glycoconjugates that play important roles
      in infection. These glycoconjugates are particularly abundant in the promastigote
      form and known to be essential for establishment of infection in the insect
      midgut and effective transmission to the mammalian host. Since they are rich in
      galactose, their biosynthesis requires an ample supply of UDP-galactose. This
      nucleotide-sugar arises from epimerisation of UDP-glucose but also from an
      uncharacterised galactose salvage pathway. In this study, we evaluated the role
      of the newly characterised UDP-sugar pyrophosphorylase (USP) of Leishmania major
      in UDP-galactose biosynthesis. Upon deletion of the USP encoding gene, L. major
      lost the ability to synthesise UDP-galactose from galactose-1-phosphate but its
      ability to convert glucose-1-phosphate into UDP-glucose was fully maintained.
      Thus USP plays a role in UDP-galactose activation but does not significantly
      contribute to the de novo synthesis of UDP-glucose. Accordingly, USP was shown to
      be dispensable for growth and glycoconjugate biosynthesis under standard growth
      conditions. However, in a mutant seriously impaired in the de novo synthesis of
      UDP-galactose (due to deficiency of the UDP-glucose pyrophosphorylase) addition
      of extracellular galactose increased biosynthesis of the cell surface
      lipophosphoglycan. Thus under restrictive conditions, such as those encountered
      by Leishmania in its natural habitat, galactose salvage by USP may play a
      substantial role in biosynthesis of the UDP-galactose pool. We hypothesise that
      USP recycles galactose from the blood meal within the midgut of the insect for
      synthesis of the promastigote glycocalyx and thereby contributes to successful
      vector infection. 

PMID- 26215060
TI  - Increased plasma CgA levels associated with nonalcoholic fatty liver disease.
AB  - BACKGROUND/AIMS: Chromogranin A (CgA), a major soluble protein released by the
      neuroendocrine system, functions as a prohormone by giving rise to several
      biologically active peptides. Our study aimed to evaluate the relationship
      between CgA levels and nonalcoholic fatty liver disease (NAFLD). MATERIALS AND
      METHODS: In total, 111 NAFLD patients and 120 healthy controls were enrolled in
      the trial. The levels of plasma CgA were quantified by an available enzyme-linked
      immunosorbent assay kit. Pearson's correlation analysis was conducted to detect
      whether CgA levels correlated with oxidative stress, insulin resistance, and
      inflammation profile. A multiple stepwise regression model was used to explore
      independent determinants for plasma CgA levels. Multivariate logistic regression
      analysis was conducted to assess whether CgA levels were independent predictors
      of NAFLD. RESULTS: The levels of plasma CgA between the case and control groups
      were significantly different (70.9+/-8.1 MUg/L vs 47.6+/-11.3 MUg/L). The levels
      of plasma CgA positively correlated with high-sensitivity C-reactive protein (hs
      CRP; p=0.000), fasting blood glucose (FBG; p=0.025), homeostasis model assessment
      of insulin resistance index (HOMA-IR; p=0.012), and malondialdehyde (MDA;
      p=0.037) levels, but negatively associated with superoxide dismutase (SOD;
      p=0.041) levels. The multiple stepwise regression model indicated that hs-CRP,
      MDA, and HOMA-IR were independent determinants for plasma CgA levels. The
      logistic regression analysis showed that plasma levels of CgA were independent
      predictors of NAFLD. CONCLUSION: Increased plasma CgA levels were associated with
      NAFLD.

PMID- 26215061
TI  - The development of a clinical score for the prediction of nonalcoholic
      steatohepatitis in patients with nonalcoholic fatty liver disease using routine
      parameters.
AB  - BACKGROUND/AIMS: To develop a clinical score for the prediction of nonalcoholic
      steatohepatitis (NASH) using routine parameters in patients with nonalcoholic
      fatty liver disease who had abnormal liver function tests and/or fatty liver
      detected by ultrasonography. MATERIALS AND METHODS: To identify parameters
      associated with the presence of NASH by evaluating anthropometric characteristics
      and routine biomarkers of 82 patients with histologically proven NAFLD and to
      develop a clinical score for predicting NASH according to the area under the
      curve of receiver operating characteristics (AUC) of parameters. RESULTS: Four
      parameters [alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), C
      reactive protein (CRP), and apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1)
      ratio] were significantly linked to NASH. The AUROCs of ALT, GGT, CRP, and
      ApoB/ApoA1 ratio for the prediction of NASH were 0.829, 0.892, 0.708, and 0.712,
      respectively. The AUROC of the combined clinical score for the prediction of NASH
      was 0.904 (95% CI, 0.885-1.002) at a cut-off of 3.8 points with a sensitivity of
      90.2%, specificity of 87.0%, positive predictive value of 88.3%, and negative
      predictive value of 91.5%. CONCLUSION: In the present study, a clinical score was
      developed for the noninvasive prediction of NASH; the score was based on a
      combination of routine biochemical parameters and was useful in distinguishing
      NASH from NAFLD.

PMID- 26215062
TI  - Prognostic markers for metastatic colon cancer patients undergoing multiple
      metastasectomies.
AB  - BACKGROUND/AIMS: Following metastasis resection, 5-year survival rate has been
      reported as approximately 40%. There is no consensus regarding prognostic factors
      related to progression-free survival after repeated metastasectomies. MATERIALS
      AND METHODS: A total of 21 patients with metastatic colorectal cancer who
      underwent repeated metastasectomies were retrospectively analyzed. The periods
      between the first and second metastasectomies and that between the second
      metastasectomy and progression were defined as metastasis-free survival 1 (MFS1)
      and metastasis-free survival 2 (MFS2), respectively. Univariate analysis was used
      to analyze factors related to MFS1 and MFS2. RESULTS: Approximately two-thirds of
      the patients had synchronous metastasis, which were localized mostly in the liver
      (90%). During a 49-months follow-up, MFS1 was 15.7 (8.4-23) months and MFS2 was
      26.3 (12.3-40.4) months. Systemic chemotherapy followed the first metastasectomy
      (p=0.01), and the recurrence site (p=0.03) was found to be related to MFS1.
      Furthermore, the number of metastases during the first metastasectomy (p=0.02),
      the type of the chemotherapy regimen administered following the first
      metastasectomy (p=0.04), and the number of metastases before the second
      metastasectomy (p=0.03) were significantly related to MFS2. CONCLUSION: Surgical
      resection is currently the most effective and curative form of therapy for
      colorectal metastasis, whenever possible. Repeated metastasectomies can be
      achieved safely in experienced centers; thus, the operability of the patients
      should be evaluated by a multidisciplinary approach during treatment.

PMID- 26215063
TI  - Mismatch repair gene expression in gastroesophageal cancers.
AB  - BACKGROUND/AIMS: Mismatch repair (MMR) genes play a critical role in maintaining
      genomic stability, and the impairment of MMR machinery is associated with
      different human cancers, mainly colorectal cancer. The purpose of our study was
      to analyze gene expression patterns of three MMR genes (MSH2, MHS6, and EXO1) in
      gastroesophageal cancers, a pathology in which the contribution of DNA repair
      genes remains essentially unclear. MATERIALS AND METHODS: A total of 45 Romanian
      patients diagnosed with sporadic gastroesophageal cancers were included in this
      study. For each patient, MMR mRNA levels were measured in biopsied tumoral (T)
      and peritumoral (PT) tissues obtained by upper endoscopy. Quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) with specific TaqMan probes was
      used to measure gene expression levels for MSH2, MSH6, and EXO1 genes. RESULTS: A
      significant association was observed for the investigated MMR genes, all of which
      were detected to be upregulated in gastroesophageal tumor samples when compared
      with paired normal samples. In the stratified analysis, the association was
      limited to gastric adenocarcinoma samples. We found no statistically significant
      associations between MMR gene expression and tumor site or histological grade.
      CONCLUSION: In our study, MSH2, MSH6, and EXO1 genes were overexpressed in
      gastroesophageal cancers. Further investigations based on more samples are
      necessary to validate our findings.

PMID- 26215064
TI  - Lack of association of two common polymorphisms rs2910164 and rs11614913 with
      susceptibility to gastric cancer: A meta-analysis.
AB  - BACKGROUND/AIMS: MicroRNAs post-transcriptionally regulate the expression of
      their target genes and their function in a wide range of physiological pathways.
      Aberrant expression of microRNAs has been implicated in the development of human
      malignant tumors. Recent reports showed that two single nucleotide polymorphisms
      (SNPs), miR-146a rs2910164 and miR-196a2 rs11614913, are associated with
      increased risk of human gastric cancer. Nevertheless, results from the published
      reports are still inconsistent and inconclusive. Thus, we conducted this meta
      analysis study to further evaluate the effects of these two SNPs on
      susceptibility to human gastric cancer. MATERIALS AND METHODS: Using specific
      inclusion and exclusion criteria, we extracted data from selected studies that
      were identified from electronic databases, such as PubMed, Embase, and Wanfang.
      Odds ratio (ORs) and 95% CIs were then obtained to determine the impact of the
      two SNPs on susceptibility to human gastric cancer using the statistical software
      Stata. RESULTS: We identified six studies on rs2910164 and five reports regarding
      rs11614913 for our meta-analysis. Our data demonstrated that the two SNPs
      rs2910164 and rs11614913 do not produce any effects on the risk of human gastric
      cancer under all genetic models. CONCLUSION: There is no significant association
      between rs2910164 and rs11614913 and the risk of human gastric cancer. However,
      future studies with large and homogeneous population of patients with gastric
      cancer and well-matched controls are needed to validate these findings.

PMID- 26215065
TI  - Possible relationship between the resistin gene C-420G polymorphism and
      colorectal cancer in a Turkish population.
AB  - BACKGROUND/AIMS: In recent years, with improvements in genotyping, a possible
      relationship between obesity-related gene polymorphisms and colorectal cancer
      (CRC) has been studied. The promoter region C-420G of the resistin gene is
      believed to have an important role in the development of malignancy. We
      prospectively evaluated the possible effect of the resistin C-420G polymorphism
      on the risk and prognosis of CRC. MATERIALS AND METHODS: One hundred twenty-three
      patients with CRC and 79 healthy individuals were included in the study. Blood
      samples were genotyped, and the relationship between the resistin C-420G
      polymorphism and demographic characteristics and tumor features was evaluated.
      RESULTS: No statistically significant difference was found in genotype
      distribution between the patient and control groups and among patients in the
      means of gender, biochemical findings, and tumor characteristics (p>0.05).
      CONCLUSION: The relationship between the C-420G polymorphism and various diseases
      has been evaluated in many studies to date. With the increased importance of
      obesity in etiopathogenesis, studies have focused on CRC. According to our
      results, the GG genotype may be associated with a decreased CRC risk. Our study
      is important because to our knowledge, it is the first one to be conducted in a
      Turkish population to date, but we believe that more patients and controls are
      needed to obtain statistically significant results.

PMID- 26215066
TI  - Squamous cell carcinoma of the cecum developing in a patient with long-standing
      ulcerative colitis and a coexistent carcinoid tumor in the appendix: A case
      report.
AB  - Squamous cell carcinoma (SCC) of the colon is a rare tumor that accounts for 0.1%
      0.2% of colonic malignancies. However, pure SCC of the cecum is extremely rare.
      Although SCC of the colon is a rare complication of idiopathic inflammatory bowel
      disease (IBD), SCC of the cecum in the context of IBD has not been previously
      reported in the English literature. We report a case of the coexistence of SCC of
      the cecum and a carcinoid tumor in a 46-year-old female with long-standing pan
      ulcerative colitis. 

PMID- 26215067
TI  - Prevalence of Barrett's esophagus in Lebanon.

PMID- 26215068
TI  - How to evaluate gastroesophageal sphincter incompetence.

PMID- 26215069
TI  - Eosinophilic colitis presenting with lower gastrointestinal bleeding: An uncommon
      entity with a rare presentation.

PMID- 26215070
TI  - Important factors determining prognosis based on SUVmax in PET imaging.

PMID- 26215072
TI  - Erosion or vascular channel?

PMID- 26215071
TI  - Structure of silent transcription intervals and noise characteristics of
      mammalian genes.
AB  - Mammalian transcription occurs stochastically in short bursts interspersed by
      silent intervals showing a refractory period. However, the underlying processes
      and consequences on fluctuations in gene products are poorly understood. Here, we
      use single allele time-lapse recordings in mouse cells to identify minimal models
      of promoter cycles, which inform on the number and durations of rate-limiting
      steps responsible for refractory periods. The structure of promoter cycles is
      gene specific and independent of genomic location. Typically, five rate-limiting
      steps underlie the silent periods of endogenous promoters, while minimal
      synthetic promoters exhibit only one. Strikingly, endogenous or synthetic
      promoters with TATA boxes show simplified two-state promoter cycles. Since
      transcriptional bursting constrains intrinsic noise depending on the number of
      promoter steps, this explains why TATA box genes display increased intrinsic
      noise genome-wide in mammals, as revealed by single-cell RNA-seq. These findings
      have implications for basic transcription biology and shed light on interpreting
      single-cell RNA-counting experiments. 

PMID- 26215073
TI  - [Adverse transfusion reactions in recipients with anti-vitamin K treatment].
AB  - PURPOSE OF THE STUDY: Vitamin K antagonist treated patients are exposed to a risk
      of haemorrhage in case of overdose leading to a need for transfusion. In order to
      determine the incidence of adverse transfusion reactions in these patients, the
      reports indicating a vitamin K antagonist treatment were analyzed. PATIENTS AND
      METHODS: In the treated and transfused patient population, the diagnosis
      following the adverse transfusion reactions, the incidence, the degree of
      severity, the blood component involved and its imputability were evaluated.
      RESULTS: From January 1st 2000 to December 31st 2014, 142 reports were notified
      in 141 patients. Haemorrhage was observed in 102 cases (71.8%). Overdose of anti
      vitamin K was reported in 43 cases only (30.3%). The most frequent adverse
      transfusion reaction was the anti-erythrocyte alloimmunization (66 cases, 46.5%)
      followed by the febrile non-haemolytic reaction (37 cases, 26.1%). Most adverse
      reactions were non-severe (131 cases, 92.3%). The most involved blood component
      was the red blood cells concentrate (139 cases, 97.9%). The imputability of the
      blood product was certain in 39 cases only (27.5%). CONCLUSION: In patients
      treated with vitamin K antagonists and transfused, the anti-erythrocyte
      alloimmunization was the most frequent adverse transfusion reaction. Overdose of
      the vitamin K antagonists was notified in approximately a third of cases.

PMID- 26215074
TI  - Ground-State Electronic Structure of RC-LH1 and LH2 Pigment Assemblies of Purple
      Bacteria via the EBF-MO Method.
AB  - Light-harvesting antennas are protein-pigment complexes that play a crucial role
      in natural photosynthesis. The antenna complexes absorb light and transfer energy
      to photosynthetic reaction centers where charge separation occurs. This work
      focuses on computational studies of the electronic structure of the pigment
      networks of light-harvesting complex I (LH1), LH1 with the reaction center (RC
      LH1), and light-harvesting complex II (LH2) found in purple bacteria. As the
      pigment networks of LH1, RC-LH1, and LH2 contain thousands of atoms, conventional
      density functional theory (DFT) and ab initio calculations of these systems are
      not computationally feasible. Therefore, we utilize DFT in conjunction with the
      energy-based fragmentation with molecular orbitals method and a semiempirical
      approach employing the extended Huckel model Hamiltonian to determine the
      electronic properties of these pigment assemblies. Our calculations provide a
      deeper understanding of the electronic structure of natural light-harvesting
      complexes, especially their pigment networks, which could assist in rational
      design of artificial photosynthetic devices. 

PMID- 26215075
TI  - A conserved pi-cation and an electrostatic bridge are essential for 11R
      lipoxygenase catalysis and structural stability.
AB  - Lipoxygenases (LOXs) are lipid-peroxidizing enzymes that consist of a regulatory
      calcium- and membrane-binding PLAT (polycystin-1, lipoxygenase, alpha-toxin)
      domain and a catalytic domain. In a previous study, the crystal structure of an
      11R-LOX revealed a conserved pi-cation bridge connecting these two domains which
      could mediate the regulatory effect of the PLAT domain to the active site. Here
      we analyzed the role of residues Trp107 and Lys172 that constitute the pi-cation
      bridge in 11R-LOX along with Arg106 and Asp173-a potential salt bridge, which
      could also contribute to the inter-domain communication. According to our kinetic
      assays and protein unfolding experiments conducted using differential scanning
      fluorimetry and circular dichroism spectroscopy, mutants with a disrupted link
      display diminished catalytic activity alongside reduced stability of the protein
      fold. The results demonstrate that both these bridges contribute to the two
      domain interface, and are important for proper enzyme activation. 

PMID- 26215076
TI  - Signaling network of lipids as a comprehensive scaffold for omics data
      integration in sputum of COPD patients.
AB  - Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive
      inflammatory condition that has been linked to the dysregulation of many
      metabolic pathways including lipid biosynthesis. How lipid metabolism could
      affect disease progression in smokers with COPD remains unclear. We cross
      examined the transcriptomics, proteomics, metabolomics, and phenomics data
      available on the public domain to elucidate the mechanisms by which lipid
      metabolism is perturbed in COPD. We reconstructed a sputum lipid COPD (SpLiCO)
      signaling network utilizing active/inactive, and functional/dysfunctional lipid
      mediated signaling pathways to explore how lipid-metabolism could promote COPD
      pathogenesis in smokers. SpLiCO was further utilized to investigate signal
      amplifiers, distributers, propagators, feed-forward and/or -back loops that link
      COPD disease severity and hypoxia to disruption in the metabolism of
      sphingolipids, fatty acids and energy. Also, hypergraph analysis and calculations
      for dependency of molecules identified several important nodes in the network
      with modular regulatory and signal distribution activities. Our systems-based
      analyses indicate that arachidonic acid is a critical and early signal
      distributer that is upregulated by the sphingolipid signaling pathway in COPD,
      while hypoxia plays a critical role in the elevated dependency to glucose as a
      major energy source. Integration of SpLiCo and clinical data shows a strong
      association between hypoxia and the upregulation of sphingolipids in smokers with
      emphysema, vascular disease, hypertension and those with increased risk of lung
      cancer. 

PMID- 26215077
TI  - Unique pharmacology of tapentadol for treating acute and chronic pain.
AB  - INTRODUCTION: Even though pain is a complex process involving many different
      mediators, enzymes, receptors and ion channels, pain medications usually address
      only individual targets. Nucynta, which addresses multiple pain targets, was the
      first new centrally acting analgesic to be approved by the FDA in 2008. AREAS
      COVERED: Pharmacology: Tapentadol is a centrally acting opioid with two
      mechanisms of action, including agonism at the MU-opioid receptor (MOR) and
      inhibition of norepinephrine reuptake (NRI), producing analgesia individually and
      via a combination of both acts synergistically at the spinal and supraspinal
      levels. The pharmacokinetics of both forms of tapentadol (immediate release-IR
      and extended release-ER) is relatively predictable and stable in healthy
      individuals. Clinical efficacy: Tapentadol IR was studied in clinical trials
      involving patients mainly with postoperative pain, but also in patients suffering
      from acute low back pain and osteoarthritis-related pain. Tapentadol ER was
      approved for management of pain severe enough to require daily, around-the-clock,
      long-term opioid treatment and for which alternative treatment options are
      inadequate. EXPERT OPINION: Although future improved, well-designed prospective,
      randomized double-blind controlled studies are needed to determine both the
      relative efficacy of tapentadol and its safety, we believe that tapentadol has
      the potential to become a uniquely suited opioid medication in the multi-modal
      management of moderate-to-severe acute and chronic pain conditions.

PMID- 26215078
TI  - Pupil Response to Threat in Trauma-Exposed Individuals With or Without PTSD.
AB  - An infrequently studied and potentially promising physiological marker for
      posttraumatic stress disorder (PTSD) is pupil response. This study tested the
      hypothesis that pupil responses to threat would be significantly larger in trauma
      exposed individuals with PTSD compared to those without PTSD. Eye-tracking
      technology was used to evaluate pupil response to threatening and neutral images.
      Recruited for participation were 40 trauma-exposed individuals; 40.0% (n = 16)
      met diagnostic criteria for PTSD. Individuals with PTSD showed significantly more
      pupil dilation to threat-relevant stimuli compared to the neutral elements
      (Cohen's d = 0.76), and to trauma-exposed controls (Cohen's d = 0.75). Pupil
      dilation significantly accounted for 12% of variability in PTSD after time
      elapsed since most recent trauma, cumulative violence exposure, and trait anxiety
      were statistically adjusted. The final logistic regression model was associated
      with 85% of variability in PTSD status and correctly classified 93.8% of
      individuals with PTSD and 95.8% of those without. Pupil reactivity showed promise
      as a physiological marker for PTSD.

PMID- 26215079
TI  - The Synthesis, Characterization, Crystal Structure and Photophysical Properties
      of a New Meso-BODIPY Substituted Phthalonitrile.
AB  - A new highly fluorescent difluoroboradipyrromethene (BODIPY) dye (4) bearing an
      phthalonitrile group at meso-position of the chromophoric core has been
      synthesized starting from 4-(4-meso-dipyrromethene-phenoxy)phthalonitrile (3)
      which was prepared by the oxidation of 4-(2-meso-dipyrromethane
      phenoxy)phthalonitrile (2). The structural, electronic and photophysical
      properties of the prepared dye molecule were investigated. The final product
      exhibit noticeable spectroscopic properties which were examined by its absorption
      and fluorescence spectra. The original compounds prepared in the reaction pathway
      were characterized by the combination of FT-IR, (1)H and (13)C NMR, UV-vis and MS
      spectral data. It has been calculated; molecular structure, vibrational
      frequencies, (1)H and (13)C NMR chemical shifts and HOMO and LUMO energies of the
      title compound by using B3LYP method with 6-311++G(dp) basis set, as well. The
      final product (4) was obtained as single crystal which crystallized in the
      triclinic space group P-1 with a = 9.0490 (8) A, b = 10.5555 (9) A, c = 11.7650
      (9) A, alpha = 77.024 (6) degrees , beta = 74.437 (6) degrees , gamma = 65.211
      (6) degrees  and Z = 2. The crystal structure has intermolecular C-H...F weak
      hydrogen bonds. The singlet oxygen generation ability of the dye (4) was also
      investigated in different solvents to determine of using in photodynamic therapy
      (PDT).

PMID- 26215080
TI  - Fluorescence Detection of Single DNA Molecules.
AB  - Single-molecule detection (SMD) and single-molecule fluorescence resonance energy
      transfer (smFRET) were conducted using Cy3- and Cy5-labeled single-strand DNAs
      (ssDNAs) either immobilized on substrates or encapsulated in microdroplets. High
      quality fluorescent images were obtained using a total internal reflection
      fluorescence microscope (TIRFM). In the substrate system, deposition of a low
      concentration of fluorescence molecules on substrates through electrostatic
      adsorption showed that most of the fluorescence spots were single molecules, and
      the mean value of signal to noise ratio (S/N) reached 6.9 +/- 0.34. smFRET
      analysis was conducted through immobilization of donor- and acceptor-labeled
      oligonucleotides on substrates. In the droplet system, fluorophor-labeled
      oligonucleotides were injected into T-type microfluidics. Single and double
      fluorophor-labeled DNA molecules encapsulated in droplets were detected, the FRET
      efficiency and inter-dye distance of a single donor-acceptor pair were measured
      accurately. smFRET was conducted detailedly in the tortuous channel for the first
      time.

PMID- 26215081
TI  - A New Schiff Base Chemodosimeter for Fluorescent Imaging of Ferric Ions in Living
      Cells.
AB  - A new and efficient chemodosimeter for ferric ions has been developed. The visual
      and fluorescent behaviors of the compound toward various metal ions were
      investigated: ferric ions are distinguished from other cations by selective color
      change and unusual fluorescence enhancement in mixed aqueous solution.
      Fluorescence microscopy experiments showed that this receptor is effective for
      detection of Fe(3+) in vitro, developing a good image of the biological
      organelles. The sensing mechanism is shown to involve a hydrolysis process. 

PMID- 26215082
TI  - Silk coating on a bioactive ceramic scaffold for bone regeneration: effective
      enhancement of mechanical and in vitro osteogenic properties towards load-bearing
      applications.
AB  - Bioactive ceramic scaffolds represent competitive choices for clinical bone
      reconstruction, but their widespread use is restricted by inherent brittleness
      and weak mechanical performance under load. This study reports the development of
      strong and tough bioactive scaffolds suitable for use in load-bearing bone
      reconstruction. A strong and bioactive ceramic scaffold (strontium-hardystonite
      gahnite) is combined with single and multiple coating layers of silk fibroin to
      enhance its toughness, producing composite scaffolds which match the mechanical
      properties of cancellous bone and show enhanced capacity to promote in vitro
      osteogenesis. Also reported for the first time is a comparison of the coating
      effects obtained when a polymeric material is coated on ceramic scaffolds with
      differing microstructures, namely the strontium-hardystonite-gahnite scaffold
      with high-density struts as opposed to a conventional ceramic scaffold, such as
      biphasic calcium phosphate, with low-density struts. The results show that silk
      coating on a unique ceramic scaffold can lead to simple and effective enhancement
      of its mechanical and biological properties to suit a wider range of applications
      in clinical bone reconstruction, and also establish the influence of ceramic
      microstructure on the effectiveness of silk coating as a method of reinforcement
      when applied to different types of ceramic bone graft substitutes. Copyright (c)
      2015 John Wiley & Sons, Ltd.

PMID- 26215084
TI  - A Priori Estimation of Organic Reaction Yields.
AB  - A thermodynamically guided calculation of free energies of substrate and product
      molecules allows for the estimation of the yields of organic reactions. The non
      ideality of the system and the solvent effects are taken into account through the
      activity coefficients calculated at the molecular level by perturbed-chain
      statistical associating fluid theory (PC-SAFT). The model is iteratively trained
      using a diverse set of reactions with yields that have been reported previously.
      This trained model can then estimate a priori the yields of reactions not
      included in the training set with an accuracy of ca. +/-15 %. This ability has
      the potential to translate into significant economic savings through the
      selection and then execution of only those reactions that can proceed in good
      yields.

PMID- 26215083
TI  - Can an Arthroplasty Registry Help Decrease Transfusions in Primary Total Joint
      Replacement? A Quality Initiative.
AB  - BACKGROUND: Standardized care plans are effective at controlling cost and
      quality. Registries provide insights into quality and outcomes for use of
      implants, but most registries do not combine implant and care quality data. In
      2012, several Michigan area hospitals and a major insurance provider formed a
      voluntary statewide total joint database/registry, the Michigan Arthroplasty
      Registry Collaborative Quality Initiative (MARCQI), to collect procedural,
      hospital, discharge, and readmission data. Noting substantial variation in
      transfusion practices after total joint arthroplasty (TJA) in our institutions,
      we used these prospectively collected data to examine whether awareness and
      education of the American Association of Blood Banks' (AABB) transfusion
      guidelines would result in decreased transfusions. QUESTIONS/PURPOSES: (1) Can an
      established arthroplasty registry help implement a quality initiative (QI)
      designed to decrease the proportion of transfused postoperative patients
      undergoing TJA? (2) Do data-driven transfusion protocols decrease length of stay
      without increasing ischemic complications (myocardial infarctions and
      cerebrovascular accidents)? (3) Are decreased transfusion proportions associated
      with decreased readmissions, nonischemic morbidity (including deep vein
      thrombosis and deep prosthetic infection), and mortality in postoperative
      patients who had undergone TJA? METHODS: After reviewing data from the recently
      established MARCQI registry, the orthopaedic department noticed many
      discrepancies and practice variances regarding blood transfusions among their
      providers. In October 2013, a QI was implemented to raise awareness of the
      discrepancies and education about the AABB guidelines was presented at the
      monthly orthopaedic service line meeting. A total of 1872 TJA cases were
      reviewed; 50 were excluded for incomplete data and two for intraoperative
      transfusions for the period before education (May 2012 to June 2013, n = 1240)
      and after education (November 2013 to April 2014, n = 580). Data collected
      included gender, age, length of stay, body mass index, preoperative hemoglobin
      level, lowest postoperative hemoglobin level during admission, transfusion
      status, number of units transfused, ischemic and nonischemic morbidity, hospital
      readmissions within 90 days, and mortality. Pre- and post-QI transfusion
      proportions were calculated. Chi-square test, Student's t-test, and a
      multivariate analysis were performed to compare differences in transfusion
      proportions for patients with a postoperative hemoglobin >= 8 g/dL. RESULTS:
      Overall, the percentage of patients transfused with a postoperative hemoglobin >=
      8 g/dL decreased 80% (6.5% [71 of 1092] versus 1.3% [seven of 538]; odds ratio,
      5.3; 95% confidence interval, 2.4-11.6; p < 0.001) after the educational
      intervention. Before education, 16% (195 of 1240) of all patients undergoing TJA
      were transfused, whereas 6.5% (71 of 1092) were outside recommended AABB
      guidelines (hemoglobin >= 8 g/dL). In the 6 months after QI initiation, overall
      transfusions decreased to 6% (35 of 580) with 1.3% (seven of 538) having a
      hemoglobin >= 8 g/dL. The mean length of stay for nontransfused patients was
      shorter (2.4 days +/- 0.9 versus 3.3 days +/- 1.1, p < 0.001) and ischemic
      complications did not differ between groups (0.32% [four of 1240] versus 0.34%
      [two of 580], p = 0.61). Before and after education, neither the number of
      readmissions (5.4% [67 of 1240] versus 4.7% [27 of 580], p = 0.50) nor morbidity
      (3.6% [45 of 1240] versus 2.4% [14 of 580], p = 0.17) differed between time
      periods. There were no deaths. CONCLUSIONS: Simple education and awareness of
      quality practices drive safety and compliance. The impact can be immediate and
      lasting. Arthroplasty registries that combine procedural and care quality data
      are vital and may be used for important data-driven QIs. LEVEL OF EVIDENCE: Level
      III, therapeutic study.

PMID- 26215085
TI  - Pharmacokinetic digital phantoms for accuracy assessment of image-based dosimetry
      in (177)Lu-DOTATATE peptide receptor radionuclide therapy.
AB  - Patient-specific image-based dosimetry is considered to be a useful tool to limit
      toxicity associated with peptide receptor radionuclide therapy (PRRT). To
      facilitate the establishment and reliability of absorbed-dose response
      relationships, it is essential to assess the accuracy of dosimetry in clinically
      realistic scenarios. To this end, we developed pharmacokinetic digital phantoms
      corresponding to patients treated with (177)Lu-DOTATATE. Three individual voxel
      phantoms from the XCAT population were generated and assigned a dynamic activity
      distribution based on a compartment model for (177)Lu-DOTATATE, designed
      specifically for this purpose. The compartment model was fitted to time-activity
      data from 10 patients, primarily acquired using quantitative scintillation camera
      imaging. S values for all phantom source-target combinations were calculated
      based on Monte-Carlo simulations. Combining the S values and time-activity
      curves, reference values of the absorbed dose to the phantom kidneys, liver,
      spleen, tumours and whole-body were calculated. The phantoms were used in a
      virtual dosimetry study, using Monte-Carlo simulated gamma-camera images and
      conventional methods for absorbed-dose calculations. The characteristics of the
      SPECT and WB planar images were found to well represent those of real patient
      images, capturing the difficulties present in image-based dosimetry. The phantoms
      are expected to be useful for further studies and optimisation of clinical
      dosimetry in (177)Lu PRRT. 

PMID- 26215086
TI  - Metabolic network capacity of Escherichia coli for Krebs cycle-dependent proline
      hydroxylation.
AB  - BACKGROUND: Understanding the metabolism of the microbial host is essential for
      the development and optimization of whole-cell based biocatalytic processes, as
      it dictates production efficiency. This is especially true for redox biocatalysis
      where metabolically active cells are employed because of the cofactor/cosubstrate
      regenerative capacity endogenous in the host. Recombinant Escherichia coli was
      used for overproducing proline-4-hydroxylase (P4H), a dioxygenase catalyzing the
      hydroxylation of free L-proline into trans-4-hydroxy-L-proline with a
      ketoglutarate (a-KG) as cosubstrate. In this whole-cell biocatalyst, central
      carbon metabolism provides the required cosubstrate a-KG, coupling P4H
      biocatalytic performance directly to carbon metabolism and metabolic activity. By
      applying both experimental and computational biology tools, such as metabolic
      engineering and (13)C-metabolic flux analysis ((13)C-MFA), we investigated and
      quantitatively described the physiological, metabolic, and bioenergetic response
      of the whole-cell biocatalyst to the targeted bioconversion and identified
      possible metabolic bottlenecks for further rational pathway engineering. RESULTS:
      A proline degradation-deficient E. coli strain was constructed by deleting the
      putA gene encoding proline dehydrogenase. Whole-cell biotransformations with this
      mutant strain led not only to quantitative proline hydroxylation but also to a
      doubling of the specific trans-4-L-hydroxyproline (hyp) formation rate, compared
      to the wild type. Analysis of carbon flux through central metabolism of the
      mutant strain revealed that the increased a-KG demand for P4H activity did not
      enhance the a-KG generating flux, indicating a tightly regulated TCA cycle
      operation under the conditions studied. In the wild type strain, P4H synthesis
      and catalysis caused a reduction in biomass yield. Interestingly, the DeltaputA
      strain additionally compensated the associated ATP and NADH loss by reducing
      maintenance energy demands at comparably low glucose uptake rates, instead of
      increasing the TCA activity. CONCLUSIONS: The putA knockout in recombinant E.
      coli BL21(DE3)(pLysS) was found to be promising for productive P4H catalysis not
      only in terms of biotransformation yield, but also regarding the rates for
      biotransformation and proline uptake and the yield of hyp on the energy source.
      The results indicate that, upon a putA knockout, the coupling of the TCA-cycle to
      proline hydroxylation via the cosubstrate a-KG becomes a key factor constraining
      and a target to further improve the efficiency of a-KG-dependent
      biotransformations.

PMID- 26215087
TI  - P2 of Rice grassy stunt virus (RGSV) and p6 and p9 of Rice ragged stunt virus
      (RRSV) isolates from Vietnam exert suppressor activity on the RNA silencing
      pathway.
AB  - In Vietnam, the two main viruses that cause disease in rice are the Rice grassy
      stunt virus (RGSV) and the Rice ragged stunt virus (RRSV). Outbreaks of these two
      viruses have dramatically decreased rice production in Vietnam. Because natural
      resistance genes are unknown, an RNAi strategy may be an alternative method to
      develop resistance to RGSV and RRSV. However, this strategy will be efficient
      only if putative silencing suppressors encoded by the two viruses are
      neutralized. To identify these suppressors, we used the classical green
      fluorescent protein (GFP) agroinfiltration method in Nicotiana benthamiana. Then,
      we investigated the effects of viral candidate proteins on GFP expression and GFP
      siRNA accumulation and their interference with the short- or long-range signal of
      silencing. RGSV genes s2gp1, s5gp2, and s6gp1 and RRSV genes s5gp1, s6gp1, s9gp1,
      and s10gp1 were selected for viral silencing suppressor investigation according
      to their small molecular weight, the presence of cysteines, or the presence of a
      GW motif in related protein products. We confirmed that protein p6 of RRSV
      displays mild silencing suppressor activity and affects long-range silencing by
      delaying the systemic silencing signal. In addition, we identified two new
      silencing suppressors that displayed mild activity: p2 of RGSV and p9 of RRSV.

PMID- 26215088
TI  - DiscoGel(r) in patients with discal lumbosciatica. Retrospective results in 25
      consecutive patients.
AB  - INTRODUCTION: Discogenic lumbosciatica is a common disorder in patients between
      30 and 40 years old. Because of the frequency and socio-professional impact of
      this entity, it represents a real public health problem. DiscoGel(r) is a class
      III medical device used for nucleolysis to avoid discectomy. The goal of this
      study was to evaluate the effectiveness of this treatment in patients with
      discogenic lumbosciatica following unsuccessful conservative medical treatment.
      MATERIALS AND METHODS: This is a retrospective, single-center study including 25
      patients who were treated with DiscoGel(r) between 2010 and 2011 at Niort
      Hospital, France. The severity of lumbar and radicular pain was assessed by a
      verbal numeric scale (VNS) and patient satisfaction. Patients were classified as
      successes or failures. RESULTS: Treatment was found to reduce the severity of
      lumbar pain in 73% and of radicular pain in 80% of patients in the success group.
      Treatment was a failure in 64% of patients. A comparison of the two groups showed
      that a preoperative MODIC 2 MRI signal of the adjacent vertebral end plate was
      significantly associated with treatment failure (Chi(2)=8572, P < 0.01).
      DISCUSSION: The VNS for lumbar pain and radicular pain decreased in 42% and 50%
      of patients respectively after the use of DiscoGel(r). In our series, DiscoGel(r)
      treatment was unsuccessful for discogenic lumbosciatica in 16 patients. These
      results do not support others in the literature. A lack of statistical power
      could partly explain these results. The most important result of this study is
      found in the subgroup analysis which suggests that indications for DiscoGel(r)
      treatment could be modified in the future in relation to preoperative imaging
      data. LEVEL OF EVIDENCE: 4.

PMID- 26215089
TI  - Severe slipped capital femoral epiphysis: A French multicenter study of 186 cases
      performed by the SoFOP.
AB  - INTRODUCTION: The treatment of severe slipped capital femoral epiphysis (SCFE)
      remains controversial. Despite numerous treatments being available, the outcome
      of published studies has been variable. Recent studies emphasize that poor
      reduction of the severe SCFE is responsible for the appearance of joint cartilage
      lesions and progression towards early osteoarthritis. But surgical reduction of
      severe SCFE also results in a significant rate of necrosis. OBJECTIVE: Evaluate
      the results of various treatment strategies for severe SCFE and identify the
      optimal course of action. MATERIAL AND METHODS: This was a French multicenter
      retrospective study of severe SCFE cases (>45 degrees  displacement) evaluated a
      minimum of 12 months after treatment. The stability of the slipped epiphysis,
      type of the treatment, delay before treatment, early and short-term
      complications, Harris and WOMAC functional scores and radiological signs of
      femoroacetabular impingement (FAI) at the last review were evaluated. A total of
      186 cases of severe SCFE in 182 patients were included. One hundred and seven
      (58.7%) of these were male. The average age was 13 years. The average follow-up
      was 23 months. The average displacement was 60 degrees . The SCFE was considered
      stable in 94 cases (50.5%) and unstable in 92 cases (49.5%). The main surgical
      treatments used by the various centers were in situ fixation (ISF), lateral Dunn,
      anterior Dunn and reduction using traction or under anesthesia (for unstable
      forms). RESULTS: In the stable SCFE cases, there were 6 cases of necrosis (6.4%),
      all of which occurred after reduction by osteotomy; there were 32 cases of
      radiological FAI (34%), 30 of which occurred after ISF. The necrosis rate in the
      unstable SCFE cases was 21.7%: one (11%) after ISF, seven (19%) after anterior
      Dunn, eight (21%) after preoperative reduction and three (43%) after lateral
      Dunn. CONCLUSIONS: The results of this study confirm the diverse nature of SCFE
      treatments available and the variability of their results. When selecting a
      treatment for severe SCFE, the goal is to stop the slip and also to prevent
      osteoarthritis by correcting the hip deformities. The "anterior" Dunn procedure
      was able to achieve these two goals, while having a lower complication rate than
      the other reduction techniques.

PMID- 26215090
TI  - Surgical treatment of femoral diaphyseal fractures in children using elastic
      stable intramedullary nailing by open reduction at Yopougon Teaching Hospital.
AB  - INTRODUCTION: Elastic stable intramedullary nailing (ESIN) has transformed
      children's femoral shaft fracture treatment, but this technique requires an image
      intensifier. Without it, open reduction is used to check fracture reduction and
      pin passage. The aim of this study was to describe our techniques and to evaluate
      our results at the middle term. HYPOTHESIS: The open reduction and ESIN technique
      provides satisfactory results with few major complications. PATIENTS AND METHODS:
      This was a retrospective study that focused on femoral diaphyseal fractures
      treated in the pediatric surgery unit at Yopougon Teaching Hospital (Abidjan,
      Cote d'Ivoire) between January 2007 and December 2013. Twenty children older than
      6 years of age who underwent open reduction and ESIN without image intensifier
      assistance were included. Functional outcomes were assessed using Flynn's
      criteria. Postoperative complications and sequelae were recorded. RESULTS: At the
      16-month follow-up, the results were excellent in 11 (55%) cases, good in eight
      (40%), and poor in one (5%) case. The mean duration of surgery was 71min (range,
      57-103 min). The mean time for bone healing was 11.6 weeks (range, 7-15 weeks)
      and the average time to nail removal was 6 months. Complications included wood
      infection (n=3), skin irritation (n=3), knee stiffness (n=2), malunion (n=3),
      scar (n=5), and leg length discrepancy (n=3). DISCUSSION: Open reduction and ESIN
      yielded satisfactory results with few major complications. This method could be
      an alternative in low-income countries where the image intensifier is often
      unavailable. LEVEL OF EVIDENCE: Level IV retrospective study.

PMID- 26215091
TI  - Protective practices against zoonotic infections among rural and slum communities
      from South Central Chile.
AB  - BACKGROUND: Despite well-recognized recommendations to reduce human exposure to
      zoonotic pathogens, the use of personal and herd-level protective practices is
      inconsistent in communities where human interactions with animals are common.
      This study assessed household-level participation in rodent- (extermination,
      proper food storage, trash disposal), occupational- (preventive veterinary care,
      boot-wearing, glove-wearing), and garden-associated (restricting animal access,
      boot-wearing, glove-wearing) protective practices in farms, villages, and slums
      in the Los Rios region, Chile, where zoonotic pathogens are endemic. METHODS:
      Questionnaires administered at 422 households across 12 communities recorded
      household-level socio-demographic characteristics and participation in nine
      protective practices. Household inclusion in the analysis of occupational
      practices required having livestock and a household member with occupational
      exposure to livestock (n = 127), and inclusion in analysis of garden practices
      required having a garden and at least one animal (n = 233). The proportion of
      households participating in each protective practice was compared across
      community types through chi-square analyses. Mixed effects logistic regression
      assessed household-level associations between socio-demographic characteristics
      and participation in each protective practice. RESULTS: Most households (95.3 %)
      reported participation in rodent control, and a positive association between the
      number of rodent signs in a household and rodent extermination was observed (OR:
      1.75, 95 % CI: 1.41, 2.16). Occupational protective practices were reported in
      61.8 % of eligible households; household size (OR: 1.63, 95 % CI: 1.17, 5.84) and
      having children (OR: 0.22, 95 % CI: 0.06, 0.78) were associated with preventive
      veterinary care. Among eligible households, 73.8 % engaged in protective
      practices when gardening, and species diversity was positively associated with
      wearing boots (OR: 1.27, 95 % CI: 1.03, 1.56). Household-level participation in
      all three protective practices within any exposure category was limited (<10.4 %)
      and participation in any individual protective practice varied considerably
      within and across community types. CONCLUSIONS: The levels of participation in
      protective practices reported in this study are consistent with descriptions in
      the literature of imperfect use of methods that reduce human exposure to zoonotic
      pathogens. The wide differences across communities in the proportion of
      households participating in protective practices against human exposure to
      zoonotic pathogens, suggests that future research should identify community-level
      characteristics that influence household participation in such practices.

PMID- 26215092
TI  - Applying a perceptions and practicalities approach to understanding nonadherence
      to antiepileptic drugs.
AB  - OBJECTIVE: Nonadherence to antiepileptic drugs (AEDs) is a common cause of poor
      seizure control. This study examines whether reported adherence to AEDs is
      related to variables identified in the National Institute for Health and Clinical
      Excellence (NICE) Medicines Adherence Guidelines as being important to adherence:
      perceptual factors (AED necessity beliefs and concerns), practical factors
      (limitations in capability and resources), and perceptions of involvement in
      treatment decisions. METHODS: This was a cross-sectional study of people with
      epilepsy receiving AEDs. Participants completed an online survey hosted by the
      Epilepsy Society (n = 1,010), or as an audit during inpatient admission (n =
      118). Validated questionnaires, adapted for epilepsy, assessed reported adherence
      to AEDs (Medication Adherence Report Scale [MARS]), perceptions of AEDs (Beliefs
      about Medicines Questionnaire [BMQ]), and patient perceptions of involvement in
      treatment decisions (Treatment Empowerment Scale [TES]). RESULTS: Low adherence
      was related to AED beliefs (doubts about necessity: t(577) = 3.90, p < 0.001; and
      concerns: t(995) = 3.45, p = 0.001), reported limitations in capability and
      resources (t(589) = 7.78, p < 0.001), and to perceptions of a lack of involvement
      in treatment decisions (t(623) = 4.48, p < 0.001). In multiple logistic
      regression analyses, these factors significantly (p < 0.001) increased variance
      in reported adherence, above that which could be explained by age and clinical
      variables (seizure frequency, type, epilepsy duration, number of AEDs
      prescribed). SIGNIFICANCE: Variables identified in the NICE Medicines Adherence
      Guidelines as potentially important factors for adherence were found to be
      related to adherence to AEDs. These factors are potentially modifiable.
      Interventions to support optimal adherence to AEDs should be tailored to address
      doubts about AED necessity and concerns about harm, and to overcome practical
      difficulties, while engaging patients in treatment decisions.

PMID- 26215098
TI  - Fabricating an Accurate Implant Master Cast: A Technique Report.
AB  - The technique for fabricating an accurate implant master cast following the 12
      week healing period after Teeth in a Day(r) dental implant surgery is detailed.
      The clinical, functional, and esthetic details captured during the final master
      impression are vital to creating an accurate master cast. This technique uses the
      properties of the all-acrylic resin interim prosthesis to capture these details.
      This impression captures the relationship between the remodeled soft tissue and
      the interim prosthesis. This provides the laboratory technician with an accurate
      orientation of the implant replicas in the master cast with which a passive
      fitting restoration can be fabricated. 

PMID- 26215093
TI  - MCM8-9 complex promotes resection of double-strand break ends by MRE11-RAD50-NBS1
      complex.
AB  - MCM8-9 complex is required for homologous recombination (HR)-mediated repair of
      double-strand breaks (DSBs). Here we report that MCM8-9 is required for DNA
      resection by MRN (MRE11-RAD50-NBS1) at DSBs to generate ssDNA. MCM8-9 interacts
      with MRN and is required for the nuclease activity and stable association of MRN
      with DSBs. The ATPase motifs of MCM8-9 are required for recruitment of MRE11 to
      foci of DNA damage. Homozygous deletion of the MCM9 found in various cancers
      sensitizes a cancer cell line to interstrand-crosslinking (ICL) agents. A cancer
      derived point mutation or an SNP on MCM8 associated with premature ovarian
      failure (POF) diminishes the functional activity of MCM8. Therefore, the MCM8-9
      complex facilitates DNA resection by the MRN complex during HR repair, genetic or
      epigenetic inactivation of MCM8 or MCM9 are seen in human cancers, and genetic
      inactivation of MCM8 may be the basis of a POF syndrome. 

PMID- 26215099
TI  - S6 Kinase is essential for MYC-dependent rDNA transcription in Drosophila.
AB  - Increased rates of ribosome biogenesis and biomass accumulation are fundamental
      properties of rapidly growing and dividing malignant cells. The MYC oncoprotein
      drives growth predominantly via its ability to upregulate the ribosome biogenesis
      program, in particular stimulating the activity of the RNA Polymerase I (Pol I)
      machinery to increase ribosomal RNA (rRNA) transcription. Although MYC function
      is known to be highly dependent on the cellular signalling context, the pathways
      interacting with MYC to regulate transcription of ribosomal genes (rDNA) in vivo
      in response to growth factor status, nutrient availability and cellular stress
      are only beginning to be understood. To determine factors critical to MYC
      dependent stimulation of rDNA transcription in vivo, we performed a transient
      expression screen for known oncogenic signalling pathways in Drosophila.
      Strikingly, from the broad range of pathways tested, we found that ribosomal
      protein S6 Kinase (S6K) activity, downstream of the TOR pathway, was the only
      factor rate-limiting for the rapid induction of rDNA transcription due to
      transiently increased MYC. Further, we demonstrated that one of the mechanism(s)
      by which MYC and S6K cooperate is through coordinate activation of the essential
      Pol I transcription initiation factor TIF-1A (RRN 3). As Pol I targeted therapy
      is now in phase 1 clinical trials in patients with haematological malignancies,
      including those driven by MYC, these data suggest that therapies dually targeting
      Pol I transcription and S6K activity may be effective in treating MYC-driven
      tumours. 

PMID- 26215100
TI  - Screening a mouse liver gene expression compendium identifies modulators of the
      aryl hydrocarbon receptor (AhR).
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates the biological and toxic effects of 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD), dioxin-like compounds (DLC) as well as some drugs and endogenous
      tryptophan metabolites. Short-term activation of AhR can lead to hepatocellular
      steatosis, and chronic activation can lead to liver cancer in mice and rats.
      Analytical approaches were developed to identify biosets in a genomic database in
      which AhR activity was altered. A set of 63 genes was identified (the AhR gene
      expression biomarker) that was dependent on AhR for regulation after exposure to
      TCDD or benzo[a]pyrene and includes the known AhR targets Cyp1a1 and Cyp1b1. A
      fold-change rank-based test (Running Fisher's test; p-value <= 10(-4)) was used
      to evaluate the similarity between the AhR biomarker and a test set of 37 and 41
      biosets positive or negative, respectively for AhR activation. The test resulted
      in a balanced accuracy of 95%. The rank-based test was used to identify factors
      that activate or suppress AhR in an annotated mouse liver/mouse primary
      hepatocyte gene expression database of ~ 1850 comparisons. In addition to the
      expected activation of AhR by TCDD and DLC, AhR was activated by AP20189 and
      phenformin. AhR was suppressed by phenobarbital and 1,4-Bis[2-(3,5
      dichloropyridyloxy)] benzene (TCPOBOP) in a constitutive activated receptor (CAR)
      dependent manner and pregnenolone-16alpha-carbonitrile in a pregnane X receptor
      (PXR)-dependent manner. Inactivation of individual genes in nullizygous models
      led to AhR activation (Pxr, Ghrhr, Taf10) or suppression (Ahr, Ilst6st, Hnf1a).
      This study describes a novel screening strategy for identifying factors in mouse
      liver that perturb AhR in a gene expression compendium.

PMID- 26215101
TI  - Neonatal chlorpyrifos exposure induces loss of dopaminergic neurons in young
      adult rats.
AB  - Increasing epidemiological and toxicological evidence suggests that pesticides
      and other environmental exposures may be associated with the development of
      Parkinson's disease (PD). Chlorpyrifos (CPF) is a widely used organophosphorous
      pesticide with developmental neurotoxicity. Its neurotoxicity, notably on the
      monoamine system, suggests that exposure of CPF may induce dopaminergic neuronal
      injury. We investigated whether neonatal exposure to CPF contributes to
      initiation and progression of dopaminergic neurotoxicity and explored the
      possible underlying mechanisms. The newborn rats were administrated 5 mg/kg CPF
      subcutaneously from postnatal day (PND) 11 to PND 14 daily. The effect of CPF on
      dopaminergic neurons, microglia, astrocyte, nuclear factor-kappaB (NF-kappaB) p.
      65 and p. 38 mitogen-activated protein kinase (MAPK) signaling pathways was
      analyzed in the substantia nigra of rats at 12h, 24h, 72 h, 16d and 46 d after
      exposure. CPF-treated rats exhibited significant reduction of dopaminergic
      neurons at 16d and 46 d after exposure, and a significant increase in the
      expression of microglia and astrocytes in the substantia nigra after CPF
      exposure. Intense activation of NF-kappaB p. 65 and p. 38 MAPK inflammatory
      signaling pathways was observed. Our findings indicate that neonatal exposure to
      CPF may induce long-term dopaminergic neuronal damage in the substantia nigra
      mediated by the activation of inflammatory response via NF-kappaB p. 65 and p. 38
      MAPK pathways in the nigrostriatal system.

PMID- 26215102
TI  - Evolutionary insights from de novo transcriptome assembly and SNP discovery in
      California white oaks.
AB  - BACKGROUND: Reference transcriptomes provide valuable resources for understanding
      evolution within and among species. We de novo assembled and annotated a
      reference transcriptome for Quercus lobata and Q. garryana and identified single
      nucleotide polymorphisms (SNPs) to provide resources for forest genomicists
      studying this ecologically and economically important genus. We further performed
      preliminary analyses of genes important in interspecific divergent (positive)
      selection that might explain ecological differences among species, estimating
      rates of nonsynonymous to synonymous substitutions (d N/d S) and Fay and Wu's H.
      Functional classes of genes were tested for unusually high d N/d S or low H
      consistent with divergent positive selection. RESULTS: Our draft transcriptome is
      among the most complete for oaks, including 83,644 contigs (23,329 >= 1 kbp),
      14,898 complete and 13,778 partial gene models, and functional annotations for
      9,431 Arabidopsis orthologs and 19,365 contigs with Pfam hits. We identified 1.7
      million possible sequence variants including 1.1 million high-quality diallelic
      SNPs - among the largest sets identified in any tree. 11 of 18 functional
      categories with significantly elevated d N/d S are involved in disease response,
      including 50+ genes with d N/d S > 1. Other high-d N/d S genes are involved in
      biotic response, flowering and growth, or regulatory processes. In contrast,
      median d N/d S was low (0.22), suggesting that purifying selection influences
      most genes. No functional categories have unusually low H. CONCLUSIONS: These
      results offer preliminary support for the hypothesis that divergent selection at
      pathogen resistance are important factors in species divergence in these
      hybridizing California oaks. Our transcriptome provides a solid foundation for
      future studies of gene expression, natural selection, and speciation in Quercus.

PMID- 26215103
TI  - Multicenter study on hemorrhagic risk of heparin bridging therapy for
      periendoscopic thromboprophylaxis.
AB  - BACKGROUND: For endoscopic interventions, heparin bridging therapy is recommended
      in patients who are at high risk from interruption of antithrombotic therapy.
      Although heparin bridging has been reported to be effective in preventing
      thrombosis, several reports have raised concerns about increased risk of
      bleeding. The aim of this study was to clarify complications of hepari bridging
      therapy in therapeutic endoscopy. METHODS: A nationwide multicenter survey using
      questionnaire was performed about patients undergoing therapeutic endoscopy with
      heparin bridging. Patients who underwent therapeutic endoscopy without heparin
      bridging therapy were considered as controls. Compliance scores of heparin
      bridging therapy guideline were employed, and association was analyzed between
      the score and occurrence of post-procedural bleeding. RESULTS: The incidence of
      post-procedural bleeding was significantly higher (13.5%, 33/245) in the heparin
      group compared with the control group (2.7%, 299/11102)(p < 0.001). Thrombosis
      occurred in 1 patient each in the two groups. In the heparin group, post
      procedural bleeding was more likely to be delayed bleeding. Dose adjustment of
      heparin was a significant factor contributing to bleeding. The compliance score
      of heparin bridging therapy guideline was significantly higher in those who
      suffered bleeding. CONCLUSIONS: Heparin bridging therapy significantly increased
      the risk of post-procedural bleeding compared with the control. The bleeding risk
      was associated with greater adherence with guidelines for heparin bridging
      therapy.

PMID- 26215104
TI  - Oxygen exchange and transport in dual phase ceramic composite electrodes.
AB  - Composites consisting of a perovskite-based electronic or mixed conductor with a
      fluorite-structured ionic conductor are often used as electrodes in solid oxide
      electrochemical energy conversion devices. After sintering the materials, there
      is often evidence for inter-reaction between the two phases, or inter-diffusion
      of cations or impurities between the two phases. We studied the (18)O exchange
      properties of a composite consisting of CGO and LSCF in a 50 : 50 ratio. High
      resolution ToF-SIMS mapping reveals that the (18)O fraction at the very outer
      surface of grains of the CGO phase is much higher than expected from D* and k*
      values for the single-phase parent material. Surface compositional analysis by
      ToF-SIMS and low energy ion scattering (LEIS) spectroscopy suggests that the
      surfaces of the CGO grains in the composite do not show the impurities which
      typically segregate to the surface in single-phase CGO. Thus, the "cleaning" of
      impurities from the CGO surface by dissolution into the perovskite phase may be
      one explanation for the apparent enhanced surface exchange for CGO in these
      composites. 

PMID- 26215106
TI  - Whole-brain radiation therapy for brain metastases: detrimental or beneficial?
AB  - Stereotactic radiosurgery is frequently used, either alone or together with whole
      brain radiation therapy to treat brain metastases from solid tumors. Certain
      experts and radiation oncology groups have proposed replacing whole-brain
      radiation therapy with stereotactic radiosurgery alone for the management of
      brain metastases. Although randomized trials have favored adding whole-brain
      radiation therapy to stereotactic radiosurgery for most end points, a recent meta
      analysis demonstrated a survival disadvantage for patients treated with whole
      brain radiation therapy and stereotactic radiosurgery compared with patients
      treated with stereotactic radiosurgery alone. However the apparent detrimental
      effect of adding whole-brain radiation therapy to stereotactic radiosurgery
      reported in this meta-analysis may be the result of inhomogeneous distribution of
      the patients with respect to tumor histologies, molecular histologic subtypes,
      and extracranial tumor stages between the groups rather than a real effect.
      Unfortunately, soon after this meta-analysis was published, even as an abstract,
      use of whole-brain radiation therapy in managing brain metastases has become
      controversial among radiation oncologists. The American Society of Radiation
      Oncology recently recommended, in their "Choose Wisely" campaign, against
      routinely adding whole-brain radiation therapy to stereotactic radiosurgery to
      treat brain metastases. However, this situation creates conflict for radiation
      oncologists who believe that there are enough high level of evidence for the
      effectiveness of whole-brain radiation therapy in the treatment of brain
      metastases. 

PMID- 26215107
TI  - Enhanced recovery after surgery (ERAS) protocols for colorectal cancer in Japan.
AB  - BACKGROUND: Japan has one of the highest five-year relative survival rates for
      colorectal cancer in the world, with its own traditions of perioperative care and
      a unique insurance system. The benefits of enhanced recovery after surgery (ERAS)
      protocols in the Japanese population have yet to be clarified. METHODS: We
      evaluated 352 consecutive cases of colorectal cancer resection at Tokyo
      Metropolitan Bokutoh Hospital between July 2009 and November 2012. Of these, 95
      cases were performed according to traditional protocols (traditional group), and
      257 according to ERAS protocols (ERAS group), which were introduced to the
      hospital in July 2010. Primary endpoints included length of postoperative
      hospital stay, postoperative short-term morbidity, and rate of readmission within
      30 days. Intensive pre-admission counselling, no pre- and postoperative fasting
      (provision of oral nutrition), avoidance of sodium/fluid overload, intraoperative
      warm-air body heating, enforced postoperative mobilization, and multimodal team
      care were among the main changes brought about by the introduction of ERAS
      protocols. RESULTS: The median (interquartile range) length of postoperative
      hospital stay was 10 (10-12.75) days in the traditional group and seven (6-8)
      days in the ERAS group, i.e., a three-day reduction (p < 0.05) in the ERAS group.
      Moreover, the proportion of patients discharged within one week dramatically
      increased from 1 % to 77 % in the ERAS group. The overall incidence of grade 2
      and 3 postoperative complications according to the Clavien-Dindo classification
      was 9.5 % in the traditional group and 9.3 % in the ERAS group, and 30-day
      readmission rates were 8.3 % and 6.6 % in the traditional and ERAS groups,
      respectively. There were no significant differences between the two groups.
      Although operative time and blood loss did not differ significantly between the
      two groups, the volume of intraoperative infusion was significantly decreased in
      the ERAS group (p < 0.05), possibly due to ERAS recommendations to avoid
      dehydration (i.e., avoidance of sodium/fluid overload, no preoperative fasting).
      CONCLUSION: ERAS protocols for colorectal surgery helped reduce the length of
      postoperative hospital stay without adversely affecting morbidity, indicating
      that ERAS protocols are feasible and effective in Japanese settings as well.

PMID- 26215105
TI  - The effects of joint aspiration and intra-articular corticosteroid injection on
      flexion reflex excitability, quadriceps strength and pain in individuals with
      knee synovitis: a prospective observational study.
AB  - INTRODUCTION: Substantial weakness of the quadriceps muscles is typically
      observed in patients with arthritis. This is partly due to ongoing neural
      inhibition that prevents the quadriceps from being fully activated. Evidence from
      animal studies suggests enhanced flexion reflex excitability may contribute to
      this weakness. This prospective observational study examined the effects of joint
      aspiration and intra-articular corticosteroid injection on flexion reflex
      excitability, quadriceps muscle strength and knee pain in individuals with knee
      synovitis. METHODS: Sixteen patients with chronic arthritis and clinically active
      synovitis of the knee participated in this study. Knee pain flexion reflex
      threshold, and quadriceps peak torque were measured at baseline, immediately
      after knee joint aspiration alone and 5 +/- 2 and 15 +/- 2 days after knee joint
      aspiration and the injection of 40 mg of methylprednisolone acetate. RESULTS:
      Compared to baseline, knee pain was significantly reduced 5 (p = 0.001) and 15
      days (p = 0.009) post intervention. Flexion reflex threshold increased
      immediately after joint aspiration (p = 0.009) and 5 (p = 0.01) and 15 days (p =
      0.002) post intervention. Quadriceps peak torque increased immediately after
      joint aspiration (p = 0.004) and 5 (p = 0.001) and 15 days (p <0.001) post
      intervention. CONCLUSIONS: The findings from this study suggest that altered
      sensory output from an inflamed joint may increase flexion reflex excitability in
      humans, as has previously been shown in animals. Joint aspiration and
      corticosteroid injection may be a clinically useful intervention to reverse
      quadriceps muscle weakness in individuals with knee synovitis.

PMID- 26215109
TI  - Dual RCA: culprit or companion.

PMID- 26215108
TI  - Barriers and facilitators to physical activity amongst overweight and obese women
      in an Afro-Caribbean population: A qualitative study.
AB  - BACKGROUND: The proportion of obese women is nearly twice the proportion of obese
      men in Barbados, and physical inactivity may be a partial determinant. Using
      qualitative interviews and 'semi-structured' participant observation, the aim of
      this study was to identify modifiable barriers to physical activity and to
      explore the factors that facilitate physical activity amongst overweight and
      obese women in this low-resourced setting. METHODS: Seventeen women aged 25 to 35
      years with a BMI >=25, purposefully sampled from a population-based cross
      sectional study conducted in Barbados, were recruited in 2014 to participate in
      in-depth semi-structured interviews. Twelve of these women participated in one or
      more additional participant observation sessions in which the researcher joined
      and observed a routine activity chosen by the participant. More than 50 hours of
      participant observation data collection were accumulated and documented in field
      notes. Thematic content analysis was performed on transcribed interviews and
      field notes using the software Dedoose. RESULTS: Social, structural and
      individual barriers to physical activity were identified. Social factors related
      to gender norms and expectations. Women tended to be active with their female
      friends rather than partners or male peers, and reported peer support but also
      alienation. Being active also competed with family responsibilities and
      expectations. Structural barriers included few opportunities for active
      commuting, limited indoor space for exercise in the home, and low perceived
      access to convenient and affordable exercise classes. Several successful
      strategies associated with sustained activity were observed, including walking
      and highly social, low-cost exercise groups. Individual barriers related to
      healthy living strategies included perceptions about chronic disease and viewing
      physical activity as a possible strategy for desired weight loss but less
      effective than dieting. CONCLUSIONS: It is important to understand why women face
      barriers to physical activity, particularly in low-resourced settings, and to
      investigate how this could be addressed. This study highlights the role that
      gender norms and health beliefs play in shaping experiences of physical activity.
      In addition, structural barriers reflect a mix of resource-scarce and resource
      rich factors which are likely to be seen in a wide variety of developing
      contexts.

PMID- 26215110
TI  - Raymond syndrome and conjugate gaze palsy from a paramedian pontine infarct.

PMID- 26215111
TI  - Heterogeneous cytogenetic subgroups and outcomes in childhood acute
      megakaryoblastic leukemia: a retrospective international study.
AB  - Comprehensive clinical studies of patients with acute megakaryoblastic leukemia
      (AMKL) are lacking. We performed an international retrospective study on 490
      patients (age <=18 years) with non-Down syndrome de novo AMKL diagnosed from 1989
      to 2009. Patients with AMKL (median age 1.53 years) comprised 7.8% of pediatric
      AML. Five-year event-free (EFS) and overall survival (OS) were 43.7% +/- 2.7% and
      49.0% +/- 2.7%, respectively. Patients diagnosed in 2000 to 2009 were treated
      with higher cytarabine doses and had better EFS (P = .037) and OS (P = .003) than
      those diagnosed in 1989 to 1999. Transplantation in first remission did not
      improve survival. Cytogenetic data were available for 372 (75.9%) patients:
      hypodiploid (n = 18, 4.8%), normal karyotype (n = 49, 13.2%), pseudodiploid (n =
      119, 32.0%), 47 to 50 chromosomes (n = 142, 38.2%), and >50 chromosomes (n = 44,
      11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106,
      28.5%), +19 (n = 93, 25.0%), +8 (n = 77, 20.7%). Losses occurred in 65 patients
      (17.5%): -7 (n = 13, 3.5%). Common structural chromosomal aberrations were
      t(1;22)(p13;q13) (n = 51, 13.7%) and 11q23 rearrangements (n = 38, 10.2%);
      t(9;11)(p22;q23) occurred in 21 patients. On the basis of frequency and
      prognosis, AMKL can be classified to 3 risk groups: good risk-7p abnormalities;
      poor risk-normal karyotypes, -7, 9p abnormalities including t(9;11)(p22;q23)/MLL
      MLLT3, -13/13q-, and -15; and intermediate risk-others including
      t(1;22)(p13;q13)/OTT-MAL (RBM15-MKL1) and 11q23/MLL except t(9;11). Risk-based
      innovative therapy is needed to improve patient outcomes. 

PMID- 26215112
TI  - Novel whole blood assay for phenotyping platelet reactivity in mice identifies
      ICAM-1 as a mediator of platelet-monocyte interaction.
AB  - Testing of platelet function is central to the cardiovascular phenotyping of
      genetically modified mice. Traditional platelet function tests have been
      developed primarily for testing human samples and the volumes required make them
      highly unsuitable for the testing of mouse platelets. This limits research in
      this area. To address this problem, we have developed a miniaturized whole blood
      aggregometry assay, based on a readily accessible 96-well plate format coupled
      with quantification of single platelet depletion by flow cytometric analysis.
      Using this approach, we observed a concentration-dependent loss of single
      platelets in blood exposed to arachidonic acid, collagen, U46619 or protease
      activated receptor 4 activating peptide. This loss was sensitive to well
      established antiplatelet agents and genetic manipulation of platelet activation
      pathways. Observations were more deeply analyzed by flow cytometric imaging,
      confocal imaging, and measurement of platelet releasates. Phenotypic analysis of
      the reactivity of platelets taken from mice lacking intercellular adhesion
      molecule (ICAM)-1 identified a marked decrease in fibrinogen-dependent platelet
      monocyte interactions, especially under inflammatory conditions. Such findings
      exemplify the value of screening platelet phenotypes of genetically modified mice
      and shed further light upon the roles and interactions of platelets in
      inflammation. 

PMID- 26215114
TI  - Mycorrhizal synthesis between Lactarius deliciosus and Arbutus unedo L.
AB  - Arbutoid mycorrhizae were synthesized in vitro between Arbutus unedo L. and two
      isolates of Lactarius deliciosus. The fungal isolates were obtained from
      sporocarps collected under Pinus sylvestris and in a mixed forest stand of
      Quercus suber and Pinus pinea. Synthesis tubes filled with a mixture of
      sterilized peat, vermiculite, and perlite imbibed with nutrient solution were
      used. Two inoculation methods using solid and liquid media were tested. Shoots
      from an adult selected clone of A. unedo were used after in vitro rooting by
      auxin dipping. After 3 months of shoots transfer to the substrate, the root
      systems were examined for arbutoid mycorrhizae formation and later on ex vitro
      conditions, 9 months after acclimatization. The inoculum treatment with liquid
      medium improved the mycorrhizal development for both isolates, in vitro.
      Sterilized substrate for plant acclimatization increased the mycorrhizal
      development. The arbutoid mycorrhizae were observed in vitro as well as 9 months
      after acclimatization. Standard arbutoid mycorrhiza features were observed: pale
      yellow mantle, typical cruciform appearance, Hartig net (HN), and intracellular
      hyphal complexes, both confined to the epidermis. L. deliciosus mycorrhizae
      synthetized in vitro persisted 9 months after plant acclimatization.
      Morphological observations were confirmed by molecular techniques.

PMID- 26215113
TI  - von Willebrand factor propeptide: biology and clinical utility.
AB  - von Willebrand factor (VWF) is a large multimeric glycoprotein that mediates the
      attachment of platelets to damaged endothelium and also serves as the carrier
      protein for coagulation factor VIII (FVIII), protecting it from proteolytic
      degradation. Quantitative or qualitative defects in VWF result in von Willebrand
      disease (VWD), a common inherited bleeding disorder. VWF is synthesized with a
      very large propeptide (VWFpp) that is critical for intracellular processing of
      VWF. VWFpp actively participates in the process of VWF multimerization and is
      essential for trafficking of VWF to the regulated storage pathway. Mutations
      identified within VWFpp in VWD patients are associated with altered VWF structure
      and function. The assay of plasma VWFpp has clinical utility in assessing acute
      and chronic vascular perturbation associated with diseases such as thrombotic
      thrombocytopenic purpura, sepsis, and diabetes among others. VWFpp assay also has
      clear utility in the diagnosis of VWD subtypes, particularly in discriminating
      true type 3 subjects from type 1C (reduced plasma survival of VWF), which is
      clinically important and has implications for therapeutic treatment. 

PMID- 26215115
TI  - EUS-FNA can be an effective procedure for the transesophageal drainage of a
      patient with intra-peritoneal abscess.
AB  - Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is considered
      to be a highly beneficial and safe diagnostic tool. EUS-FNA now has a greater
      clinical impact because the technique is currently being applied for therapeutic
      as well as diagnostic purposes. The treatment of intra-peritoneal abscess after
      peptic ulcer perforation has traditionally been by surgery, especially when
      percutaneous abscess drainage is unfeasible. We report that less invasive
      drainage using EUS-FNA was useful in treating a patient with an abscess who had
      no other option but to select surgical treatment. 

PMID- 26215116
TI  - Acute infection by hepatitis E virus with a slight immunoglobulin M antibody
      response.
AB  - The anti-hepatitis E virus (HEV) immunoglobulin (Ig) M antibody response is
      generally regarded as a useful marker for diagnosing primary infection. However,
      in some cases, this antibody is not detected during the acute phase of infection.
      An 81-year-old man with stable membranous nephropathy who presented with
      asymptomatic acute liver dysfunction came to our hospital. HEV RNA of genotype 3
      was detected in his serum, and he was diagnosed with acute hepatitis E. According
      to an enzyme-linked immunosorbent assay, high-level positivity for anti-HEV IgG
      and IgA antibodies was observed, but the assay was negative for IgM antibody
      throughout the clinical course of infection. The patient was not
      immunosuppressed. We further investigated the presence of IgM antibody using two
      other polyclonal antibodies against human IgM as secondary antibodies and another
      recombinant ORF2 protein of genotype 3 as an immobilized antigen. IgM was weakly
      detected in the serum during the acute phase only by the test with the antigen of
      genotype 3. Multi-genotype antigens can detect a slight IgM antibody response;
      however, anti-HEV IgA is more useful in diagnosing primary HEV infection,
      particularly in cases with a low IgM antibody response. 

PMID- 26215117
TI  - Gender-dependent and genotype-sensitive monoaminergic changes induced by
      polychlorinated biphenyl 153 in the rat brain.
AB  - Polychlorinated biphenyls (PCBs) are present as ortho- and non-ortho-substituted
      PCBs, with most of the ortho-substituted congeners being neurotoxic. The present
      study examined effects of the ortho-substituted PCB 153 on dopamine, serotonin
      and amino acid neurotransmitters in the neostriatum of both male and female
      Wistar Kyoto (WKY) and spontaneously hypertensive rat (SHR) genotypes. PCB 153
      exposure at p8, p14 and p20 had no effects on levels of these transmitters when
      examined at p55, but led to increased levels of both homovanillic acid and 5
      hydroxyindoleacetic acid, the degradation products of dopamine and serotonin,
      respectively, in all groups except the female SHR. Immunoblotting showed that PCB
      exposure induced gender-specific decreases in dopaminergic synaptic proteins.
      These included a novel finding of decreased levels of the dopamine D5 receptor in
      both genders and genotypes, whereas male-specific changes included decreases in
      the postsynaptic density (PSD)-95 protein in the WKY and SHRs and a decrease in
      the presynaptic dopamine transporter in both the WKY and, less clearly in the
      male SHR. A female-specific tendency of increased vesicular monoamine transporter
      2 was observed in the SHRs after PCB exposure. No changes were seen in tyrosine
      hydroxylase, the cytoskeletal neurotubulin or the plasma membrane marker
      Na(+)/K(+)-ATPase in any strain. Hence, PCB-exposure led to increases in
      monoamine transmitter turnover in both male and female animals, whereas decreases
      in both pre- and postsynaptic dopaminergic proteins were predominantly seen in
      male animals. PCB 153 may therefore induce neostriatal toxicity through both
      presynaptic and postsynaptic mechanisms in both genotypes and genders, including
      effects on the aspiny interneurons, which employ the D5 receptor to mediate
      dopamine effects on interneurons in the basal ganglia. 

PMID- 26215118
TI  - Developmental exposure to manganese induces lasting motor and cognitive
      impairment in rats.
AB  - Exposure to high manganese (Mn) levels may damage the basal ganglia, leading to a
      syndrome analogous to Parkinson's disease, with motor and cognitive impairments.
      The molecular mechanisms underlying Mn neurotoxicity, particularly during
      development, still deserve further investigation. Herein, we addressed whether
      early-life Mn exposure affects motor coordination and cognitive function in
      adulthood and potential underlying mechanisms. Male Wistar rats were exposed
      intraperitoneally to saline (control) or MnCl2 (5, 10 or 20 mg/kg/day) from post
      natal day (PND) 8-12. Behavioral tests were performed on PND 60-65 and
      biochemical analysis in the striatum and hippocampus were performed on PND14 or
      PND70. Rats exposed to Mn (10 and 20 mg/kg) performed significantly worse on the
      rotarod test than controls indicating motor coordination and balance impairments.
      The object and social recognition tasks were used to evaluate short-term memory.
      Rats exposed to the highest Mn dose failed to recognize a familiar object when
      replaced by a novel object as well as to recognize a familiar juvenile rat after
      a short period of time. However, Mn did not alter olfactory discrimination
      ability. In addition, Mn-treated rats displayed decreased levels of non-protein
      thiols (e.g. glutathione) and increased levels of glial fibrillary acidic protein
      (GFAP) in the striatum. Moreover, Mn significantly increased hippocampal
      glutathione peroxidase (GPx) activity. These findings demonstrate that acute low
      level exposure to Mn during a critical neurodevelopmental period causes cognitive
      and motor dysfunctions that last into adulthood, that are accompanied by
      alterations in antioxidant defense system in both the hippocampus and striatum.

PMID- 26215120
TI  - Transiently impaired neurogenesis in MPTP mouse model of Parkinson's disease.
AB  - It is still being debated whether neurogenesis in the subventricular zone (SVZ)
      is enhanced in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      injury in the adult mouse brain. Our previous studies provided evidence that MPTP
      induces apoptosis of migrating neuroblasts (neural progenitor cells, A cells) in
      the SVZ and rostral migratory stream (RMS). We investigated cellular kinetics in
      the adult SVZ and olfactory bulb (OB) after MPTP damage. Cells were labeled with
      bromodeoxyuridine (BrdU), and the effects of MPTP on the survival and fate of
      migrating and residing neuroblasts were evaluated. Two days after BrdU labeling
      and MPTP treatment, the number of BrdU-positive cells in the SVZ and OB of MPTP
      treated mice was significantly lower than in the SVZ and OB of saline controls.
      Additionally, fewer BrdU-positive cells migrated to the OB of treated mice than
      to that of saline controls, and the cells that did migrate diffused radially into
      the granule cell layer (GCL) when observed at 7, 14, and 28 days. In the OB GCL,
      the differentiation of BrdU-positive cells into mature neurons significantly
      attenuated 14 and 28 days after MPTP injury. Moreover, the impaired neurogenesis
      was followed by a recovery of A cells in the SVZ and OB, suggesting activation of
      the self-repair process as a result of MPTP-induced depletion of BrdU-positive
      cells. Our findings clarify the kinetics underlying neurogenesis in MPTP-treated
      mice and may contribute to the development of an animal model of Parkinson's
      disease, and the demonstration of cellular kinetics in SVZ may also provide a new
      insight into assessing neurogenesis in MPTP-treated mouse. 

PMID- 26215121
TI  - Pacing Strategies of Ultracyclists in the "Race Across AMerica".
AB  - PURPOSE: To examine pacing strategies of ultracyclists competing in the Race
      Across AMerica (RAAM), the world's longest ultracycling race, covering ~4860 km
      from the West to the East coast of America. METHODS: Age, cycling speed at and
      across time stations, race distance, relative difference in altitude between time
      stations, wind velocity, wind gradient, and temperature at each time station were
      recorded for women and men competing from 2010 to 2014. Changes in cycling speed
      and power output of elite and age-group finishers were analyzed using mixed
      effects regression analyses. RESULTS: Cycling speed decreased across time
      stations for women and men where men were faster than women. Power output
      decreased across time stations in women and men and was lower for women for all
      finishers, the annual 3 fastest, and age group 60-69 y but not for age groups 18
      49 and 50-59 y. The change in temperature and altitude had an influence on
      cycling speed and power output in all finishers, the annual top 3, nonfinishers,
      and in all different age groups for both women and men but in the age group 50-59
      y altitude had no influence on cycling speed. CONCLUSIONS: Positive pacing (ie,
      decrease in speed throughout the race) seemed to be the adequate strategy in the
      RAAM. The top 3 finishers started faster and had a higher power output at the
      start than less successful competitors, achieved the highest peak cycling speeds
      and power output, and maintained peak cycling speed and power output longer
      before slowing down.

PMID- 26215119
TI  - Comparative effects of parathion and chlorpyrifos on endocannabinoid and
      endocannabinoid-like lipid metabolites in rat striatum.
AB  - Parathion and chlorpyrifos are organophosphorus insecticides (OPs) that elicit
      acute toxicity by inhibiting acetylcholinesterase (AChE). The endocannabinoids
      (eCBs, N-arachidonoylethanolamine, AEA; 2-arachidonoylglycerol, 2AG) are
      endogenous neuromodulators that regulate presynaptic neurotransmitter release in
      neurons throughout the central and peripheral nervous systems. While substantial
      information is known about the eCBs, less is known about a number of
      endocannabinoid-like metabolites (eCBLs, e.g., N-palmitoylethanolamine, PEA; N
      oleoylethanolamine, OEA). We report the comparative effects of parathion and
      chlorpyrifos on AChE and enzymes responsible for inactivation of the eCBs, fatty
      acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and changes in
      the eCBs AEA and 2AG and eCBLs PEA and OEA, in rat striatum. Adult, male rats
      were treated with vehicle (peanut oil, 2 ml/kg, sc), parathion (27 mg/kg) or
      chlorpyrifos (280 mg/kg) 6-7 days after surgical implantation of microdialysis
      cannulae into the right striatum, followed by microdialysis two or four days
      later. Additional rats were similarly treated and sacrificed for evaluation of
      tissue levels of eCBs and eCBLs. Dialysates and tissue extracts were analyzed by
      LC-MS/MS. AChE and FAAH were extensively inhibited at both time-points (85-96%),
      while MAGL activity was significantly but lesser affected (37-62% inhibition) by
      parathion and chlorpyrifos. Signs of toxicity were noted only in parathion
      treated rats. In general, chlorpyrifos increased eCB levels while parathion had
      no or lesser effects. Early changes in extracellular AEA, 2AG and PEA levels were
      significantly different between parathion and chlorpyrifos exposures.
      Differential changes in extracellular and/or tissue levels of eCBs and eCBLs
      could potentially influence a number of signaling pathways and contribute to
      selective neurological changes following acute OP intoxications.

PMID- 26215122
TI  - What is the perceived impact of Alexander technique lessons on health status,
      costs and pain management in the real life setting of an English hospital? The
      results of a mixed methods evaluation of an Alexander technique service for those
      with chronic back pain.
AB  - BACKGROUND: Randomised controlled trial evidence indicates that Alexander
      Technique is clinically and cost effective for chronic back pain. The aim of this
      mixed methods evaluation was to explore the role and perceived impact of
      Alexander Technique lessons in the naturalistic setting of an acute hospital Pain
      Management Clinic in England. METHODS: To capture changes in health status and
      resource use amongst service users, 43 service users were administered three
      widely used questionnaires (Brief Pain Inventory, MYMOP and Client Service
      Resource Inventory) at three time points: baseline, six weeks and three months
      after baseline. We also carried out 27 telephone interviews with service users
      and seven face-to-face interviews with pain clinic staff and Alexander Technique
      teachers. Quantitative data were analysed using descriptive statistics and
      qualitative data were analysed thematically. RESULTS: Those taking Alexander
      Technique lessons reported small improvements in health outcomes, and condition
      related costs fell. However, due to the non-randomised, uncontrolled nature of
      the study design, changes cannot be attributed to the Alexander Technique
      lessons. Service users stated that their relationship to pain and pain management
      had changed, especially those who were more committed to practising the
      techniques regularly. These changes may explain the reported reduction in pain
      related service use and the corresponding lower associated costs. CONCLUSIONS:
      Alexander Technique lessons may be used as another approach to pain management.
      The findings suggests that Alexander Technique lessons can help improve self
      efficacy for those who are sufficiently motivated, which in turn may have an
      impact on service utilisation levels.

PMID- 26215123
TI  - New Eugenol Glucoside-based Derivative Shows Fungistatic and Fungicidal Activity
      against Opportunistic Candida glabrata.
AB  - A new series of glucosides modified in their saccharide units were synthesized,
      evaluated against Candida sp., and compared to prototype 1, an eugenol tetracetyl
      glucoside previously synthesized and shown to be active against Candida glabrata.
      Among the new glucosides, benzyl derivative 5 was the most promising, showing
      fungistatic activity at IC50 18.1 MUm against Candida glabrata (threefold higher
      than fluconazole) and fungicidal activity with a low IC90 value of 36.2 MUm.
      Moreover, the cytotoxic activity of compound 5 (CC50 : 580.9 MUm), tested in
      peripheral blood mononuclear cells, suggests its potential as an agent to treat
      Candida glabrata infections, with a selectivity index of 32. The new eugenol
      glucoside 5 may be considered as a novel structural pattern in the development of
      new anti-Candida drugs.

PMID- 26215125
TI  - Pragmatic Randomized Trials Without Standard Informed Consent?: A National
      Survey.
AB  - BACKGROUND: Significant debate surrounds the issue of whether written consent is
      necessary for pragmatic randomized, controlled trials (RCTs) with low risk.
      OBJECTIVE: To assess the U.S. public's views on alternatives to written consent
      for low-risk pragmatic RCTs. DESIGN: National experimental survey (2 * 2
      factorial design) examining support for written consent versus general
      notification or verbal consent in 2 research scenarios. SETTING: Web-based survey
      conducted in December 2014. PARTICIPANTS: 2130 U.S. adults sampled from a
      nationally representative, probability-based online panel (response rate, 64.0%).
      MEASUREMENTS: Respondent's recommendation to an ethics review board and personal
      preference as a potential participant on how to obtain consent or notification in
      the 2 research scenarios. RESULTS: Most respondents in each of the 4 groups
      (range, 60.3% to 71.5%) recommended written informed consent, and personal
      preferences were generally in accord with that advice. Most (78.9%) believed that
      the pragmatic RCTs did not pose additional risks, but 62.5% of these respondents
      would still recommend written consent. In contrast, a substantial minority in all
      groups (28.5% to 39.7%) recommended the alternative option (general notification
      or verbal consent) over written consent. LIMITATION: Framing effects could have
      affected respondents' attitudes, and nonrespondents may have differed in levels
      of trust toward research or health care institutions. CONCLUSION: Most of the
      public favored written informed consent over the most widely advocated
      alternatives for low-risk pragmatic RCTs; however, a substantial minority favored
      general notification or verbal consent. PRIMARY FUNDING SOURCE: Time-sharing
      Experiments for the Social Sciences and Intramural Research Program of the
      National Institutes of Health Clinical Center.

PMID- 26215124
TI  - Liver-infiltrating CD8(+) lymphocytes as prognostic factor for tumour recurrence
      in hepatitis C virus-related hepatocellular carcinoma.
AB  - BACKGROUND: Chronic liver inflammation and immune/inflammatory response promote
      hepatocellular carcinoma. The aim of this study was to characterize the immune
      status of HCV-related cirrhosis in patients with hepatocellular carcinoma (HCV
      HCC) as compared to HCV patients without hepatocellular carcinoma. METHOD: Immune
      markers (CD3, CD4, CD8, CD20, CD56, TCRgammadelta, FoxP3) and gene expression
      profiles (CD8alpha, CD8beta, FoxP3, IL-6, IFN-gamma, perforin, RANTES) were
      analysed in a test cohort by immunohistochemistry and quantitative RT-PCR
      analysis on serial non-tumorous and tumorous tissues. RESULTS: Immune micro
      environment was more inflammatory in HCV-HCC than HCV cirrhotic livers. The
      number of CD3(+) , CD4(+) , CD8(+) and CD20(+) liver-infiltrating lymphocytes was
      significantly higher, whereas the number of CD56(+) cells was significantly lower
      in HCV-HCC compared to HCV cirrhotic parenchyma. These differences were
      restricted to fibrous septa for CD4(+) and CD20(+) cells and to nodular
      parenchyma for CD8(+) cells. Gene expressions of CD8alpha, FoxP3 and RANTES were
      also significantly higher in HCV-HCC than in HCV cirrhosis. Interestingly, in a
      large cohort of 63 HCV-HCC patients. The number of CD8(+) cells >=100/field was
      associated with significant higher tumour recurrence (P = 0.003) and lower
      overall survival (P = 0.05) at 5 years. CONCLUSION: High densities of liver
      infiltrating lymphocytes in HCV-HCC cirrhotic parenchyma prevail inflammatory
      conditions and could contribute to tumorigenesis and tumour recurrence. These
      results could contribute towards better clinical evaluation of patients
      susceptible for HCC recurrence after curative surgery.

PMID- 26215126
TI  - The Chagas disease domestic transmission cycle in Guatemala: Parasite-vector
      switches and lack of mitochondrial co-diversification between Triatoma dimidiata
      and Trypanosoma cruzi subpopulations suggest non-vectorial parasite dispersal
      across the Motagua valley.
AB  - Parasites transmitted by insects must adapt to their vectors and reservoirs.
      Chagas disease, an American zoonosis caused by Trypanosoma cruzi, is transmitted
      by several species of triatomines. In Central America, Triatoma dimidiata is a
      widely dispersed vector found in sylvatic and domestic habitats, with distinct
      populations across the endemic region of Guatemala. Our aim was to test the
      strength of association between vector and parasite genetic divergence in
      domestic environments. Microsatellite (MS) loci were used to characterize
      parasites isolated from T. dimidiata (n=112) collected in domestic environments.
      Moderate genetic differentiation was observed between parasites north and south
      of the Motagua Valley, an ancient biogeographic barrier (FST 0.138, p=0.009).
      Slightly reduced genotypic diversity and increased heterozygosity in the north
      (Allelic richness (Ar)=1.00-6.05, FIS -0.03) compared to the south (Ar=1.47-6.30,
      FIS 0.022) suggest either a selective or demographic process during parasite
      dispersal. Based on parasite genotypes and geographic distribution, 15 vector
      specimens and their parasite isolates were selected for mitochondrial co
      diversification analysis. Genetic variability and phylogenetic congruence were
      determined with mitochondrial DNA sequences (10 parasite maxicircle gene
      fragments and triatomine ND4+CYT b). A Mantel test as well as phylogenetic,
      network and principal coordinates analyses supported at least three T. dimidiata
      haplogroups separated by geographic distance across the Motagua Valley.
      Maxicircle sequences showed low T. cruzi genetic variability (pi nucleotide
      diversity 0.00098) with no evidence of co-diversification with the vector, having
      multiple host switches across the valley. Sylvatic Didelphis marsupialis captured
      across the Motagua Valley were found to be infected with T. cruzi strains sharing
      MS genotypes with parasites isolated from domiciliated triatomines. The current
      parasite distribution in domestic environments can be explained by multiple
      parasite-host switches between vector populations and selection or bottleneck
      processes across the Motagua Valley, with a possible role for didelphids in
      domestic transmission. 

PMID- 26215127
TI  - Agent-based mathematical modeling as a tool for estimating Trypanosoma cruzi
      vector-host contact rates.
AB  - The parasite Trypanosoma cruzi, spread by triatomine vectors, affects over 100
      mammalian species throughout the Americas, including humans, in whom it causes
      Chagas' disease. In the U.S., only a few autochthonous cases have been documented
      in humans, but prevalence is high in sylvatic hosts (primarily raccoons in the
      southeast and woodrats in Texas). The sylvatic transmission of T. cruzi is spread
      by the vector species Triatoma sanguisuga and Triatoma gerstaeckeri biting their
      preferred hosts and thus creating multiple interacting vector-host cycles. The
      goal of this study is to quantify the rate of contacts between different host and
      vector species native to Texas using an agent-based model framework. The contact
      rates, which represent bites, are required to estimate transmission coefficients,
      which can be applied to models of infection dynamics. In addition to quantitative
      estimates, results confirm host irritability (in conjunction with host density)
      and vector starvation thresholds and dispersal as determining factors for vector
      density as well as host-vector contact rates. 

PMID- 26215128
TI  - Effectiveness of hyperbaric oxygen for experimental treatment of schistosomiasis
      mansoni using praziquantel-free and encapsulated into liposomes: assay in adult
      worms and oviposition.
AB  - The treatment of schistosomiasis depends on a single drug: praziquantel (PZQ).
      However, this treatment presents limitations such as low and/or erratic
      bioavailability that can contribute to cases of tolerance. Improvements to the
      available drug are urgently needed and studies with a controlled system of drug
      release, like liposomes, have been gaining prominence. The present study
      evaluated the activity and synergy between liposomal-praziquantel (lip.PZQ) and
      hyperbaric oxygen therapy (HBO). Mice received doses of 60 or 100mg/kg PZQ or
      lip.PZQ, 50 days post-infection, and after the treatment, were exposed to HBO (3
      atmosphere absolute - ATA) for 1h. The viability of adult worms and oviposition
      were analyzed, by necropsy and Kato-Katz examination performed after 15 days of
      treatment. A concentration of 100mg/kg of lip.PZQ+HBO was more effective (48.0%
      reduction of worms, 83.3% reduction of eggs/gram of feces) and 100% of the mice
      had altered of oograms (indicating interruption of oviposition) compared to other
      treatments and to the Control group (infected and untreated). It is known that
      PZQ requires participation of the host immune system to complete its
      antischistosomal activity and that HBO is able to stimulate the immune system.
      The drug became more available in the body when incorporated into liposomes and,
      used with HBO, the HBO worked as an adjuvant. This explains the decreases of
      oviposition and worms recovered form hepatic portal system.

PMID- 26215129
TI  - DDT and pyrethroid resistance status and laboratory evaluation of bio-efficacy of
      long lasting insecticide treated nets against Culex quinquefasciatus and Culex
      decens in Ghana.
AB  - Nuisance from Culex mosquitoes in Ghana has a serious negative impact on the
      standard of living in many urban communities. In addition, a perceived lack of
      efficacy of long lasting insecticide treated nets (LLINs) against nuisance
      mosquitoes contributes to their discontinued use. This again compromises malaria
      control, even if Anopheles species themselves would still be susceptible to the
      insecticides used. Control strategies involve pyrethroid insecticides but
      information on Culex mosquito susceptibility to these insecticides is limited. A
      nationwide survey was conducted to address this problem. In adults,
      susceptibility to permethrin, deltamethrin and DDT as well as enzyme activity and
      kdr mutation were determined. Cone and tunnel bioassay were also carried out to
      determine the efficacy of LLINs against the mosquitoes. Culex quinquefasciatus
      and Culex decens were identified in the study area. Higher deltamethrin and DDT
      resistance and relatively low permethrin resistance were observed in both
      species. High enzyme activities and kdr mutations were observed in C.
      quinquefasciatus but not in C. decens. However, reduced efficacy of LLINs was
      observed in both mosquito species. This adds up to the evidence of the spread of
      pyrethroid resistance in mosquitoes and its negative impact on control
      strategies.

PMID- 26215130
TI  - Real-time PCR for detection of Strongyloides stercoralis in human stool samples
      from Cote d'Ivoire: diagnostic accuracy, inter-laboratory comparison and patterns
      of hookworm co-infection.
AB  - Human infections with the helminth species Strongyloides stercoralis encompass a
      wide clinical spectrum, ranging from asymptomatic carriage to life-threatening
      disease. The diagnosis of S. stercoralis is cumbersome and the sensitivity of
      conventional stool microscopy is low. New molecular tools have been developed to
      increase sensitivity. We compared the diagnostic accuracy of real-time PCR with
      microscopy for the detection of S. stercoralis and hookworm in human stool
      samples, and investigated the inter-laboratory agreement of S. stercoralis
      specific real-time PCR in two European laboratories. Stool specimens from 256
      randomly selected individuals in rural Cote d'Ivoire were examined using three
      microscopic techniques (i.e. Kato-Katz, Koga agar plate (KAP) and Baermann (BM)).
      Additionally, ethanol-fixed stool aliquots were subjected to molecular diagnosis.
      The prevalence of S. stercoralis and hookworm infection was 21.9% and 52.0%,
      respectively, whilst co-infections were detected in 35 (13.7%) participants. The
      diagnostic agreement between real-time PCR and microscopy was excellent when both
      KAP and BM tested positive for S. stercoralis, but was considerably lower when
      only one microscopic technique was positive. The sensitivity of KAP, BM and real
      time PCR for detection of S. stercoralis as compared to a combination of all
      diagnostic techniques was 21.4%, 37.5% and 76.8%, respectively. The inter
      laboratory agreement of S. stercoralis-specific PCR was substantial (kappa=0.63,
      p<0.001). We conclude that a combination of real-time PCR and stool microscopy
      shows high accuracy for S. stercoralis diagnosis. Besides high sensitivity, PCR
      may also enhance specificity by reducing microscopic misdiagnosis of
      morphologically similar helminth larvae (i.e. hookworm and S. stercoralis) in
      settings where both helminth species co-exist.

PMID- 26215131
TI  - Fluorinated Nanocarbons Cytotoxicity.
AB  - As the research in nanotechnology progresses, there will eventually be an influx
      in the number of commercial products containing different types of nanomaterials.
      This phenomenon might damage our health and environment if the nanomaterials used
      are found to be toxic and they are released into the waters when the products
      degrade. In this study, we investigated the cytotoxicity of fluorinated
      nanocarbons (CXFs), a group of nanomaterials which can find applications in solid
      lubricants and lithium primary batteries. Our cell viability findings indicated
      that the toxicological effects induced by the CXF are dependent on the dose,
      size, shape, and fluorine content of the CXF. In addition, we verified that CXFs
      have insignificant interactions with the cell viability assays
      methylthiazolyldiphenyl-tetrazolium bromide (MTT) and water-soluble tetrazolium
      salt (WST-8), thus suggesting that the cytotoxicity data obtained are unlikely to
      be affected by CXF-induced artifacts and the results will be reliable. 

PMID- 26215133
TI  - Acquired bilateral telangiectatic macularis eruptiva perstans on the arms of
      Asian men: A common but unrecognized disorder.

PMID- 26215132
TI  - Heterozygous modulation of TGF-beta signaling does not influence Muller glia cell
      reactivity or proliferation following NMDA-induced damage.
AB  - The stimulation of progenitor or stem cells proliferation in the retina could be
      a therapeutic avenue for the treatment of various ocular neurodegenerative
      disorders. Muller glia cells have been discussed to represent a progenitor cell
      population in the adult retina. In the brain, TGF-beta signaling regulates the
      fate of stem cells; however, its role in the vertebrate retina is unclear. We
      therefore investigated whether manipulation of the TGF-beta signaling pathway is
      sufficient to promote Muller glia cell proliferation and subsequently their trans
      differentiation into retinal neurons. To this end, we used mice with heterozygous
      deficiency of the essential TGF-beta receptor type II or of the inhibitory
      protein SMAD7, in order to down- or up-regulate the activity of TGF-beta
      signaling, respectively. Excitotoxic damage was applied by intravitreal N-methyl
      D-aspartate injection, and BrdU pulse experiments were used to label
      proliferative cells. Although we successfully stimulated Muller glia cell
      reactivity, our findings indicate that a moderate modulation of TGF-beta
      signaling is not sufficient to provoke Muller glia cell proliferation. Hence, TGF
      beta signaling in the retina might not be the essential causative factor to
      maintain mammalian Muller cells in a quiescent, non-proliferative state that
      prevents a stem cell-like function. 

PMID- 26215134
TI  - Evaluation of promising algal strains for sustainable exploitation coupled with
      CO2 fixation.
AB  - The photosynthetic activity of three microalgae, Chlamydomonas reinhardtii,
      Chlorella AU1, Scenedesmus AU1, and six cyanobacteria, Spirulina platensis,
      Anabaena cylindrica, Oscillatoria AU1, Nostoc muscurum, Synechococcus AU1,
      Synechocystis sp. PCC6803, was investigated. Strains S. platensis, Scenedesmus
      AU1 sp. and Chlorella AU1 sp. showed the highest fluorescence quenching than
      other strains tested. Thus, these were selected for CO2 mitigation analysis in a
      designed tubular photobioreactor system at 0.06%, 6%, 12%, 18% and 24% CO2
      concentrations. Spirulina showed maximum biomass productivity of 1.03 g L(-1) d(
      1) with the highest CO2 fixation rate of 0.678 g [Formula: see text] L(-1) d(-1)
      at 6% CO2 concentration. The maximum protein content (66.63%) was also achieved
      in Spirulina sp. at 6% CO2 concentration. Thus, Spirulina could be utilized as a
      source of protein supplement coupled with CO2 fixation. Maximum carbohydrate
      proportion (51.71%) was noted with Scenedesmus AU1 sp. at 12% CO2. Scenedesmus
      AU1 sp. also accumulated the maximum lipid content (25.07%) at 6% CO2
      concentration, which was further analysed for biodiesel production. The extracted
      Scenedesmus oil was mainly rich in short chain fatty acids (C-16 : 0, C-18:1, C
      18:2, C-18:3) which is an ideal combination for efficient biodiesel. Thus, this
      is vital in helping to choose Scenedesmus as a biodiesel feedstock, coupled with
      CO2 fixation.

PMID- 26215135
TI  - Quality of Life after Young Ischemic Stroke of Mild Severity Is Mainly Influenced
      by Psychological Factors.
AB  - BACKGROUND: Long-term prognosis in terms of quality of life (QoL) in young stroke
      patients is of importance because they usually have a long life expectancy and
      extensive daily life demands. We aimed at determining which medical and
      psychological factors influence the QoL in young stroke patients (<50 years),
      after long-term follow-up. METHODS: Young ischemic stroke patients admitted to
      the St. Elisabeth Hospital and the TweeSteden Hospital, Tilburg, the Netherlands,
      between 2000 and 2010 were included. One hundred seventy patients and 61 controls
      filled out the following questionnaires: (1) the Hospital Anxiety and Depression
      Scale, (2) the Fatigue Assessment Scale, and (3) the shortened World Health
      Organization Quality of Life scale. Using linear multiple regression analysis, we
      assessed the factors influencing QoL. RESULTS: QoL did not differ significantly
      between patients (median modified Rankin Scale score at follow-up, 0) and
      controls after a mean follow-up of 4.5 (standard deviation, 2.8) years. The
      presence of excessive fatigue was associated with lower scores on all domains of
      the QoL (P <= .003), but not for general health domain (P = .010). Similarly,
      depression was associated with worse QoL on the physical (P = .004) and
      psychological (P = .001) domains and anxiety with lower scores on the
      psychological (P < .001) QoL domain. No relationship was found between stroke
      specific factors and QoL. CONCLUSIONS: Fatigue and to a lesser extent depression
      and anxiety affect the QoL in young adults after ischemic stroke of mild
      severity. Therefore, young stroke patients should be informed about, screened,
      and, if possible, treated for fatigue, depression, and anxiety.

PMID- 26215136
TI  - Endovascular Treatment of Ruptured Large or Wide-Neck Basilar Tip Aneurysms
      Associated with Moyamoya Disease Using the Stent-Assisted Coil Technique.
AB  - BACKGROUND: Endovascular coiling is preferred to surgical clipping for the
      treatment of basilar tip aneurysms (BTAs) associated with moyamoya disease (MMD).
      However, there are few reports addressing the safety of stent treatment of
      aneurysms located on unaffected arteries in MMD patients. We report our
      experiences of stent-assisted coil embolization for ruptured large or wide-neck
      BTAs associated with MMD. METHODS: A retrospective review was conducted of 5
      patients with ruptured BTAs associated with MMD treated by stent-assisted coil
      from January 2010 to December 2013 in our hospital. All presented with
      subarachnoid hemorrhage, and the diagnosis was confirmed by digital subtraction
      angiography. The procedure-related complications, immediate angiographic results,
      and clinical and angiographic follow-ups were analyzed. RESULTS: Successful
      embolization was performed without procedure-related complications in all 5
      patients, of whom 3 were treated by single stent-assisted coiling, and the others
      were treated by Y-configured stent technique. Immediate angiographic results
      showed complete occlusion in 2 patients, neck residual in 1, and partial
      occlusion in 2. Postoperative angiographic follow-ups were obtained in all 5
      cases at a mean time of 17.6 +/- 9.3 months (range, 6-28 months). Follow-up
      angiographic examinations demonstrated total occlusion without in-stent
      restenosis in all cases, and all the patients reported good outcomes (modified
      Rankin Scale score, 0-2). CONCLUSIONS: Endovascular embolization using stent
      assisted coiling proved to be a safe and efficient treatment for ruptured large
      or wide-neck BTAs associated with MMD; however, the long-term safety still
      remains to be confirmed.

PMID- 26215137
TI  - Assessment of bilateral cerebral peduncular infarction: Magnetic resonance
      imaging, clinical features, and prognosis.
AB  - BACKGROUND: Bilateral cerebral peduncular infarction (BCPI) is an extremely rare
      neurological disorder, and related literature is scarce. This study investigated
      the clinical manifestations, magnetic resonance imaging (MRI) features and
      prognosis of BCPI. METHOD: We retrospectively reviewed the clinical features, MRI
      and magnetic resonance angiography manifestations, and prognosis of 14 patients
      with BCPI, confirmed by diffusion-weighted MRI from 5050 cerebral infarction
      patients at our medical center from January 2007 to June 2013. RESULT: Eleven of
      the 14 (78.6%) patients had quadriplegia and 9 (64.3%) had decreased
      consciousness. At the most severe stage, the National Institutes of Health Stroke
      Scale scores ranged from grades 4 to 26 (mean grade, 18.9). Eleven (78.6%) cases
      were caused by large artery atherosclerosis. Besides the bilateral cerebral
      peduncle, the pons (85.7%) and cerebellum (42.9%) were the other infarct
      locations. Twelve (85.7%) patients had vertebrobasilar artery occlusion or severe
      stenosis, and 12 (85.7%) did not have collateral patency of the posterior
      cerebral artery. Thirteen (92.9%) patients had poor prognosis and 9 of them died.
      OCCLUSION: BCPI is a very rare disorder and associated with severe
      vertebrobasilar artery stenosis or occlusion without collateral patency of the
      posterior communicating artery. It has a very poor prognosis.

PMID- 26215138
TI  - Improving Efficiency of Interventional Service by Lean Six Sigma.

PMID- 26215139
TI  - Different gap junction-propagated effects on cisplatin transfer result in
      opposite responses to cisplatin in normal cells versus tumor cells.
AB  - Previous work has shown that gap junction intercellular communication (GJIC)
      enhances cisplatin (Pt) toxicity in testicular tumor cells but decreases it in
      non-tumor testicular cells. In this study, these different GJIC-propagated
      effects were demonstrated in tumor versus non-tumor cells from other organ
      tissues (liver and lung). The downregulation of GJIC by several different
      manipulations (no cell contact, pharmacological inhibition, and siRNA
      suppression) decreased Pt toxicity in tumor cells but enhanced it in non-tumor
      cells. The in vivo results using xenograft tumor models were consistent with
      those from the above-mentioned cells. To better understand the mechanism(s)
      involved, we studied the effects of GJIC on Pt accumulation in tumor and non
      tumor cells from the liver and lung. The intracellular Pt and DNA-Pt adduct
      contents clearly increased in non-tumor cells but decreased in tumor cells when
      GJIC was downregulated. Further analysis indicated that the opposite effects of
      GJIC on Pt accumulation in normal versus tumor cells from the liver were due to
      its different effects on copper transporter1 and multidrug resistance-associated
      protein2, membrane transporters attributed to intracellular Pt transfer. Thus,
      GJIC protects normal organs from cisplatin toxicity while enhancing it in tumor
      cells via its different effects on intracellular Pt transfer. 

PMID- 26215140
TI  - Functionalized PHB granules provide the basis for the efficient side-chain
      cleavage of cholesterol and analogs in recombinant Bacillus megaterium.
AB  - BACKGROUND: Cholesterol, the precursor of all steroid hormones, is the most
      abundant steroid in vertebrates and exhibits highly hydrophobic properties,
      rendering it a difficult substrate for aqueous microbial biotransformations. In
      the present study, we developed a Bacillus megaterium based whole-cell system
      that allows the side-chain cleavage of this sterol and investigated the
      underlying physiological basis of the biocatalysis. RESULTS: CYP11A1, the side
      chain cleaving cytochrome P450, was recombinantly expressed in the Gram-positive
      soil bacterium B. megaterium combined with the required electron transfer
      proteins. By applying a mixture of 2-hydroxypropyl-beta-cyclodextrin and Quillaja
      saponin as solubilizing agents, the zoosterols cholesterol and 7
      dehydrocholesterol, as well as the phytosterol beta-sitosterol could be
      efficiently converted to pregnenolone or 7-dehydropregnenolone. Fluorescence
      microscopic analysis revealed that cholesterol accumulates in the carbon and
      energy storage-serving poly(3-hydroxybutyrate) (PHB) bodies and that the membrane
      proteins CYP11A1 and its redox partner adrenodoxin reductase (AdR) are likewise
      localized to their surrounding phospholipid/protein monolayer. The capacity to
      store cholesterol was absent in a mutant strain devoid of the PHB-producing
      polymerase subunit PhaC, resulting in a drastically decreased cholesterol
      conversion rate, while no effect on the expression of the recombinant proteins
      could be observed. CONCLUSION: We established a whole-cell system based on B.
      megaterium, which enables the conversion of the steroid hormone precursor
      cholesterol to pregnenolone in substantial quantities. We demonstrate that the
      microorganism's PHB granules, aggregates of bioplastic coated with a
      protein/phospholipid monolayer, are crucial for the high conversion rate by
      serving as substrate storage. This microbial system opens the way for an
      industrial conversion of the abundantly available cholesterol to any type of
      steroid hormones, which represent one of the biggest groups of drugs for the
      treatment of a wide variety of diseases.

PMID- 26215141
TI  - Development of a Canadian socioeconomic status index for the study of health
      outcomes related to environmental pollution.
AB  - BACKGROUND: Socioeconomic status (SES) is an important determinant of health and
      potential modifier of the effects of environmental contaminants. There has been a
      lack of comprehensive indices for measuring overall SES in Canada. Here, a more
      comprehensive SES index is developed aiming to support future studies exploring
      health outcomes related to environmental pollution in Canada. METHODS: SES
      variables (n = 22, Census Canada 2006) were selected based on: cultural
      identities, housing characteristics, variables identified in Canadian
      environmental injustice studies and a previous deprivation index (Pampalon
      index). Principal component analysis with a single varimax rotation (factor
      loadings >= ?60?) was performed on SES variables for 52974 census dissemination
      areas (DA). The final index was created by averaging the factor scores per DA
      according to the three components retained. The index was validated by examining
      its association with preterm birth (gestational age < 37 weeks), term low birth
      weight (LBW, <2500 g), small for gestational age (SGA, <10 percentile of birth
      weight for gestational age) and PM2.5 (particulate matter <= 2.5 MUm) exposures
      in Edmonton, Alberta (1999-2008). RESULTS: Index values exhibited a relatively
      normal distribution (median = 0.11, mean = 0.0, SD = 0.58) across Canada. Values
      in Alberta tended to be higher than in Newfoundland and Labrador, Northwest
      Territories and Nunavut (Pearson chi-square p < 0.001 across provinces). Lower
      quintiles of our index and the Pampalon's index confirmed know associations with
      a higher prevalence of LBW, SGA, preterm birth and PM2.5 exposure. Results with
      our index exhibited greater statistical significance and a more consistent
      gradient of PM2.5 levels and prevalence of pregnancy outcomes. CONCLUSIONS: Our
      index reflects more dimensions of SES than an earlier index and it performed
      superiorly in capturing gradients in prevalence of pregnancy outcomes. It can be
      used for future research involving environmental pollution and health in Canada.

PMID- 26215142
TI  - Rapid and sensitive identification of marine bacteria by an improved in situ DNA
      hybridization chain reaction (quickHCR-FISH).
AB  - Catalyzed reporter deposition-fluorescence in situ hybridization (CARD-FISH) with
      rRNA-targeted oligonucleotide probes has significantly improved the
      identification of microorganisms in various environmental samples. However, one
      of the major constraints of CARD-FISH is the low probe penetration due to the
      high molecular weight of the horseradish peroxidase (HRP) label. Recently, this
      limitation has been overcome by a novel signal amplification approach termed in
      situ DNA-hybridization chain reaction (in situ DNA-HCR). In this study, we
      present an improved and accelerated in situ DNA-HCR protocol (quickHCR-FISH) with
      increased signal intensity, which was approximately 2 times higher than that of
      standard in situ DNA-HCR. In addition, the amplification time was only 15 min for
      the extension of amplifier probes from the initiator probe compared to 2h in the
      original protocol. The quickHCR-FISH was successfully tested for the
      quantification of marine bacteria with low rRNA contents in both seawater and
      sediment samples. It was possible to detect the same number of marine bacteria
      with quickHCR-FISH compared to CARD-FISH within only 3h. Thus, this newly
      developed protocol could be an attractive alternative to CARD-FISH for the
      detection and visualization of microorganisms in their environmental context.

PMID- 26215143
TI  - [Maintenance treatment in opioid-dependent patients with migration background].
AB  - BACKGROUND: No regional analyses regarding opioid-dependent patients in
      maintenance treatment with a migration background have so far been performed in
      German-speaking countries. OBJECTIVES: This study examined patients with and
      without a migration background regarding socioeconomic parameters,
      characteristics of dependency and attitude towards opiate maintenance treatment
      (OMT). MATERIAL AND METHODS: From May to October 2011 patients in OMT from all of
      the 20 psychiatry clinics and 110 physician practices in Berlin with a licence to
      provide OMT were included in this analysis. RESULTS: Out of the 986 participating
      patients, 956 gave information on migration background and of these, 204 (21.3 %)
      originated from a country other than Germany. Compared to patients without a
      migration background, their participation in a maintenance program was
      significantly shorter and they more often expressed a desire to end OMT and
      wanted a limited duration of OMT. CONCLUSION: The differences regarding duration
      of OMT and the wish to end OMT can reflect a stronger desire for abstinence and a
      different attitude towards maintenance treatment of patients with a migration
      background.

PMID- 26215145
TI  - [Cranial nerve palsy and ageusia caused by carotid artery dissection].

PMID- 26215144
TI  - [High resolution manometry study of pharyngeal function in patients with myotonic
      dystrophy].
AB  - BACKGROUND: Patients with myotonic dystrophy (MD) are known to suffer from
      oropharyngeal dysphagia and esophageal motility disorders, which are often the
      cause of aspiration pneumonia. So far only little is known about the pharyngeal
      contractility and the function of the upper esophageal sphincter in these
      patients, in particular only few data are available for manometric investigations
      allowing assessment of the pharyngeal pressure build-up during swallowing. The
      aim of this study was to collect such data in patients with MD using high
      resolution manometry. METHOD: In two patients with MD high resolution manometry
      studies were performed during swallowing and phonation to determine pressure
      dependent parameters. The results were compared with normal values from healthy
      subjects. RESULTS: In both patients a reduced pressure in the entire pharynx
      during swallowing was determined. The duration of the contraction in the
      velopharynx and tongue base region was shortened. The structural course of the
      swallowing process and the opening and closing functions of the upper esophageal
      sphincter were regular. During realization of closed vowels a reduced pressure
      build-up in the velopharyngeal region was observed. CONCLUSION: The force of
      contraction and the associated pharyngeal pressure build-up during swallowing
      were reduced resulting in an incomplete clearing of the pharynx. Beside myopathic
      disorders, neuromuscular disorders also have to be considered. The functional
      course of the swallowing process and the swallowing pattern was retained. The
      reduced pressure build-up in the velopharyngeal region can be considered as the
      cause for rhinophonia. To evaluate the pharyngeal function in patients with MD,
      high resolution manometry is a useful tool for assessing the pharyngeal function
      besides the basic diagnostics.

PMID- 26215146
TI  - [Visual snow].

PMID- 26215147
TI  - Rethinking the roles of CRP, cAMP, and sugar-mediated global regulation in the
      Vibrionaceae.
AB  - Many proteobacteria modulate a suite of catabolic genes using the second
      messenger cyclic 3', 5'-AMP (cAMP) and the cAMP receptor protein (CRP). Together,
      the cAMP-CRP complex regulates target promoters, usually by activating
      transcription. In the canonical model, the phosphotransferase system (PTS), and
      in particular the EIIA(Glc) component for glucose uptake, provides a mechanistic
      link that modulates cAMP levels depending on glucose availability, resulting in
      more cAMP and activation of alternative catabolic pathways when glucose is
      unavailable. Within the Vibrionaceae, cAMP-CRP appears to play the classical role
      in modulating metabolic pathways; however, it also controls functions involved in
      natural competence, bioluminescence, pheromone signaling, and colonization of
      animal hosts. For this group of marine bacteria, chitin is an ecologically
      relevant resource, and chitin's monomeric sugar N-acetylglucosamine (NAG)
      supports robust growth while also triggering regulatory responses. Recent studies
      with Vibrio fischeri indicate that NAG and glucose uptake share EIIA(Glc), yet
      the responses of cAMP-CRP to these two carbon sources are starkly different.
      Moreover, control of cAMP levels appears to be more dominantly controlled by
      export and degradation. Perhaps more surprisingly, although CRP may require cAMP,
      its activity can be controlled in response to glucose by a mechanism independent
      of cAMP levels. Future studies in this area promise to shed new light on the role
      of cAMP and CRP. 

PMID- 26215148
TI  - Oral narratives in monolingual and bilingual preschoolers with SLI.
AB  - BACKGROUND: The body of literature on narratives of bilingual children with and
      without specific language impairment (SLI) is growing. However, little is known
      about the narrative abilities of bilingual preschool children with SLI and their
      patterns of growth. AIMS: To determine the similarities and differences in
      narrative abilities between preschoolers with and without SLI who are either
      monolingual or bilingual at two time points. METHODS & PROCEDURES: Forty children
      completed a narrative retell task in English at two test points. The mean ages
      were 52 and 58 months at Times 1 and 2, respectively. We examined performance on
      measures of narrative macrostructure (narrative information) and microstructure
      (sentence length, number of different words, verb accuracy, first mentions) in
      monolingual and bilingual children with and without SLI. The bilingual children
      were from diverse first-language backgrounds and all spoke English most of the
      time. OUTCOMES & RESULTS: A series of repeated-measures analyses of variance was
      used with language ability (typical development or SLI) and bilingual status
      (monolingual versus bilingual) as the between-subjects factors and time (Times 1
      or 2) as the within-subjects factor. Results indicated a significant main effect
      of time for four measures (i.e., Information Score, lexical diversity, sentence
      length and verb accuracy). The between-subjects analyses indicated a significant
      difference between the typically developing children and the children with SLI in
      all measures and a significant difference between monolingual and bilingual
      children for verb accuracy only. CONCLUSIONS & IMPLICATIONS: This study showed
      that all four groups of children showed growth over a 6-month period and that
      bilingual children exposed predominantly to English in the home performed
      similarly to their monolingual peers in measures of narrative information,
      sentence length, number of different words and first mentions.

PMID- 26215149
TI  - A novel mutation within the lactase gene (LCT): the first report of congenital
      lactase deficiency diagnosed in Central Europe.
AB  - BACKGROUND: Congenital lactase deficiency is an extremely rare gastrointestinal
      disorder characterized by neonatal-onset watery diarrhoea and failure to thrive.
      We present the first genetically confirmed case of congenital lactase deficiency
      in Central Europe. CASE PRESENTATION: After an uneventful pregnancy and birth, a
      male newborn of consanguineous parents of Turkish origin presented with watery
      diarrhoea. On day 17, he was admitted to hospital with weight loss, hypertonic
      dehydration, and metabolic acidosis. Additionally, the patient showed an elevated
      calcium concentration in blood and urine as well as nephrocalcinosis. Diarrhoea
      stopped during intravenous rehydration and when feeding a glucose-, galactose-,
      and lactose-free formula. Therefore, glucose-galactose-malabsorption was assumed.
      However, genetic testing of the SGLT1 (SLC5A1) gene was negative and, indeed,
      feeding maltodextrine did not result in recurrence of diarrhoea. In contrast,
      lactose feeding immediately caused watery diarrhoea, suggesting congenital
      lactase deficiency. Genetic testing of the LCT gene revealed homozygosity for a 1
      bp deletion in exon 8 (c.3448delT). Because of the nature of the mutation,
      causing a frame shift and a premature termination of translation, congenital
      lactase deficiency was confirmed and intestinal biopsies were unnecessary. The
      patient's general condition improved substantially on a lactose-free diet,
      including hypercalcaemia, hypercalciuria, and nephrocalcinosis which, however,
      only disappeared after months. CONCLUSION: This case demonstrates (a) that
      congenital lactase deficiency should be considered in cases of severe neonatal
      diarrhoea, (b) that intestinal biopsies can be avoided in typical cases that are
      confirmed by genetic testing, and

PMID- 26215150
TI  - On differences in radiosensitivity estimation: TCP experiments versus survival
      curves. A theoretical study.
AB  - We have compared two methods of estimating the cellular radiosensitivity of a
      heterogeneous tumour, namely, via cell-survival and via tumour control
      probability (TCP) pseudo-experiments. It is assumed that there exists intra
      tumour variability in radiosensitivity and that the tumour consists predominantly
      of radiosensitive cells and a small number of radio-resistant cells.Using a multi
      component, linear-quadratic (LQ) model of cell kill, a pseudo-experimental cell
      survival versus dose curve is derived. This curve is then fitted with a mono
      component LQ model describing the response of a homogeneous cell population. For
      the assumed variation in radiosensitivity it is shown that the composite pseudo
      experimental survival curve is well approximated by the survival curve of cells
      with uniform radiosensitivity.For the same initial cell radiosensitivity
      distribution several pseudo-experimental TCP curves are simulated corresponding
      to different fractionation regimes. The TCP model used accounts for clonogen
      proliferation during a fractionated treatment. The set of simulated TCP curves is
      then fitted with a mono-component TCP model. As in the cell survival experiment
      the fit with a mono-component model assuming uniform radiosensitivity is shown to
      be highly acceptable.However, the best-fit values of cellular radiosensitivity
      produced via the two methods are very different. The cell-survival pseudo
      experiment yields a high radiosensitivity value, while the TCP pseudo-experiment
      shows that the dose-response is dominated by the most resistant sub-population in
      the tumour, even when this is just a small fraction of the total. 

PMID- 26215151
TI  - Complement factor H R1210C among Japanese patients with age-related macular
      degeneration.
AB  - PURPOSE: To evaluate the genotype distribution of a rare age-related macular
      degeneration (AMD)-susceptibility variant, complement factor H (CFH) R1210C,
      among a large Japanese cohort with AMD. METHODS: One thousand three hundred and
      sixty-four Japanese patients with neovascular AMD were evaluated. We screened for
      CFH R1210C (rs121913059) by genotyping with the Taqman method; the mutation was
      confirmed by Sanger sequencing. We also searched for this mutation in the human
      genome variant database, which contains the whole-exome sequencing data for 1208
      Japanese individuals. The detailed characteristics of patients with this mutation
      were reviewed. RESULTS: The mean age of the patients was 74.5 years (standard
      deviation 8.7); men accounted for 71.8 % of the patients. The CFH R1210C variant
      was found in only 1 of the 1364 AMD patients, and was heterozygous (minor allele
      frequency (MAF) = 0.037 %); it was not found in any of the 1208 individuals in
      the control group (MAF = 0 %). The patient with CFH R1210C was a 70-year-old
      woman whose main complaint was visual loss in the right eye. Dilated fundus
      examination, optical coherence tomography, and fluorescein and indocyanine
      angiography revealed polypoidal choroidal neovasculopathy (PCV), but no drusen in
      either eye. Despite treatment, her visual acuity had decreased to 1/50 by 6.8
      years after her first visit. CONCLUSIONS: The CFH R1210C variant was found to be
      rare among Japanese patients with AMD. The patient with the mutation did have the
      PCV subtype, but no drusen formation. Considering their ethnicity-specific
      nature, such rare variants should be studied by use of next-generation sequencing
      for each ethnicity.

PMID- 26215152
TI  - Intravitreal liposomal amphotericin B for treatment of endogenous candida
      endophthalmitis.
AB  - PURPOSE: To evaluate the outcomes of intravitreal liposomal amphotericin B (L
      AmB) for treatment of endogenous candida endophthalmitis. METHODS: Medical
      records of four patients with endogenous candida endophthalmitis treated with
      intravitreal L-AmB injection alone or combined with vitrectomy were reviewed.
      RESULTS: Endogenous candida endophthalmitis developed in two patients after
      gastrointestinal surgery, in one patient with sepsis, and in one patient
      undergoing systemic chemotherapy for metastatic breast cancer. Three eyes of two
      patients exhibited toxic uveitis following repetitive intravitreal injection of
      amphotericin B deoxycholate (AmB-D, 10 MUg/0.1 ml). The other patients had
      general health issues that restricted the use of AmB-D due to the potential risk
      of systemic toxicity. Seven eyes underwent intravitreal injection of L-AmB (10
      MUg/0.1 ml) with or without vitrectomy. In these patients, intraocular
      inflammation and vitreous opacities resolved, and chorioretinal infiltrates
      evolved into fibrotic scars. Visual acuity improved and stabilized in all eyes
      during the follow-up period. CONCLUSIONS: Intravitreal L-AmB seems to be well
      tolerated and effective in the treatment of endogenous candida endophthalmitis,
      and may be a reasonable alternative for patients who cannot endure the side
      effects or toxicity associated with conventional AmB-D therapy.

PMID- 26215153
TI  - The genome of the truffle-parasite Tolypocladium ophioglossoides and the
      evolution of antifungal peptaibiotics.
AB  - BACKGROUND: Two major mycoparasitic lineages, the family Hypocreaceae and the
      genus Tolypocladium, exist within the fungal order, Hypocreales. Peptaibiotics
      are a group of secondary metabolites almost exclusively described from
      Trichoderma species of Hypocreaceae. Peptaibiotics are produced by nonribosomal
      peptide synthetases (NRPSs) and have antibiotic and antifungal activities.
      Tolypocladium species are mainly truffle parasites, but a few species are insect
      pathogens. RESULTS: The draft genome sequence of the truffle parasite
      Tolypocladium ophioglossoides was generated and numerous secondary metabolite
      clusters were discovered, many of which have no known putative product. However,
      three large peptaibiotic gene clusters were identified using phylogenetic
      analyses. Peptaibiotic genes are absent from the predominantly plant and insect
      pathogenic lineages of Hypocreales, and are therefore exclusive to the largely
      mycoparasitic lineages. Using NRPS adenylation domain phylogenies and
      reconciliation of the domain tree with the organismal phylogeny, it is
      demonstrated that the distribution of these domains is likely not the product of
      horizontal gene transfer between mycoparasitic lineages, but represents
      independent losses in insect pathogenic lineages. Peptaibiotic genes are less
      conserved between species of Tolypocladium and are the product of complex
      patterns of lineage sorting and module duplication. In contrast, these genes are
      more conserved within the genus Trichoderma and consistent with diversification
      through speciation. CONCLUSIONS: Peptaibiotic NRPS genes are restricted to
      mycoparasitic lineages of Hypocreales, based on current sampling. Phylogenomics
      and comparative genomics can provide insights into the evolution of secondary
      metabolite genes, their distribution across a broader range of taxa, and their
      possible function related to host specificity.

PMID- 26215154
TI  - Instruments for reproducible setting of defects in cartilage and harvesting of
      osteochondral plugs for standardisation of preclinical tests for articular
      cartilage regeneration.
AB  - BACKGROUND: Standardisation is required in research, so are approval procedures
      for advanced therapy medical products and other procedures for articular
      cartilage therapies. The process of creating samples needs to be reproducible.
      The aim of this study was to design, create and validate instruments (1) to
      create reproducible and accurate defects and (2) to isolate samples in the shape
      of osteochondral cylinders in a quick, reliable and sterile manner. METHODS:
      Adjustable instruments were created: a crown mill with a resolution of 0.05 mm
      and a front mill to create defects in articular cartilage and subchondral bone.
      The instruments were tested on knee joints of pigs from the slaughterhouse; 48
      defects were created and evaluated. A punching machine was designed to harvest
      osteochondral plugs. These were validated in an in vivo animal study. RESULTS:
      The instruments respect the desired depth of 0.5 and 1.5 mm when creating the
      defects, depending on whether the person using the instrument is highly
      experienced (0.451 mm; confidence interval (CI): 0.390 mm; 0.512 mm and 1.403 mm;
      CI: 1.305 mm; 1.502 mm) or less so (0.369 mm; CI: 0.297 mm; 0.440 mm and 1.241
      mm; CI: 1.141 mm; 1.341 mm). Eighty samples were taken from knee joints of
      Gottingen Minipigs with this punching technique. The time needed for the
      harvesting of the samples was 7.52 min (+/-2.18 min), the parallelism of the
      sides of the cylinders deviated by -0.63 degrees  (CI: -1.33 degrees ; 0.08
      degrees ) and the surface of the cartilage deviated from the perpendicularity by
      4.86 degrees  (CI: 4.154 degrees ; 5.573 degrees ). In all assessed cases, a
      sterile procedure was observed. CONCLUSIONS: Instruments and procedures for
      standardised creation and validation of defects in articular cartilage and
      subchondral bone were designed. Harvesting of samples in the shape of
      osteochondral cylinders can now be performed in a quick, reliable and sterile
      manner. The presented instruments and procedures can serve as helpful steps
      towards standardised operating procedures in the field of regenerative therapies
      of articular cartilage in research and for regulatory requirements.

PMID- 26215155
TI  - Secure Cloud-Based Solutions for Different eHealth Services in Spanish Rural
      Health Centers.
AB  - BACKGROUND: The combination of eHealth applications and/or services with cloud
      technology provides health care staff-with sufficient mobility and accessibility
      for them-to be able to transparently check any data they may need without having
      to worry about its physical location. OBJECTIVE: The main aim of this paper is to
      put forward secure cloud-based solutions for a range of eHealth services such as
      electronic health records (EHRs), telecardiology, teleconsultation, and
      telediagnosis. METHODS: The scenario chosen for introducing the services is a set
      of four rural health centers located within the same Spanish region. iCanCloud
      software was used to perform simulations in the proposed scenario. We chose
      online traffic and the cost per unit in terms of time as the parameters for
      choosing the secure solution on the most optimum cloud for each service. RESULTS:
      We suggest that load balancers always be fitted for all solutions in
      communication together with several Internet service providers and that
      smartcards be used to maintain identity to an appropriate extent. The solutions
      offered via private cloud for EHRs, teleconsultation, and telediagnosis services
      require a volume of online traffic calculated at being able to reach 2 Gbps per
      consultation. This may entail an average cost of ?500/month. CONCLUSIONS: The
      security solutions put forward for each eHealth service constitute an attempt to
      centralize all information on the cloud, thus offering greater accessibility to
      medical information in the case of EHRs alongside more reliable diagnoses and
      treatment for telecardiology, telediagnosis, and teleconsultation services.
      Therefore, better health care for the rural patient can be obtained at a
      reasonable cost.

PMID- 26215156
TI  - The effects of two common edible herbs, Ipomoea aquatica and Enhydra fluctuans,
      on cadmium-induced pathophysiology: a focus on oxidative defence and anti
      apoptotic mechanism.
AB  - BACKGROUND: Ipomoea aquatica (Convolvulaceae) and Enhydra fluctuans (Asteraceae),
      two aquatic vegetables, are traditionally used against heavy metal toxicity in
      traditional medicines in India. The present study aimed to explore the protective
      role of edible (aqueous) extracts of I. aquatica (AEIA) and E. fluctuans (AEEF)
      against Cd-intoxication. METHODS: The extracts were chemically standardized by
      spectroscopic and HPLC analysis. The cytoprotective roles of AEIA and AEEF were
      measured on mouse hepatocytes. The effect on redox status were measured after
      incubating the hepatocytes with CdCl2 (30 MUM) along with AEIA or AEEF (400
      MUg/ml). The effects on the expressions of apoptotic signal proteins were
      estimated. The protective roles of AEIA or AEEF were measured by in vivo assay in
      mice. Haematological, serum biochemical, tissue redox status, Cd bioaccumulation
      and histological parameters were evaluated to estimate the protective role of
      AEIA or AEEF (100 mg/kg) against CdCl2 (4 mg/kg) intoxication. RESULTS:
      Phytochemical analysis revealed presence of substantial quantities of phenolics,
      flavonoids, saponins, carbohydrates and ascorbic acid in AEIA or AEEF. CdCl2
      treated murine hepatocytes showed a gradual reduction of cell viability in a
      concentration dependent manner with an IC50 of ~30 MUM. CdCl2 treated hepatocytes
      exhibited significantly enhanced levels (p < 0.01) of ROS production, lipid
      peroxidation, protein carbonylation and NADPH oxidase with concomitant depletion
      (p < 0.01) of antioxidant enzymes and GSH. However, AEIA or AEEF treatment along
      with CdCl2 significantly restored the aforementioned parameters in murine
      hepatocytes near to normalcy. Besides, AEIA or AEEF significantly counteracted (p
      < 0.05-0.01) with ROS mediated alteration of transcription levels of signal
      proteins viz. Bcl-2, BAD, Cyt-C, Caspases, Fas and Bid. In in vivo bioassay,
      CdCl2 treatment caused significantly high Cd bioaccumulation and oxidative stress
      in the liver, kidney, heart, brain and testes in mice. In addition, the
      haematological and serum biochemical parameters were significantly altered in the
      CdCl2 treated animals. Simultaneous administration of AEIA or AEEF could
      significantly restore the tested parameters to the near-normal status.
      CONCLUSION: The extracts would offer the overall protective effect via
      counteracting with Cd mediated oxidative stress and/or promoting the elimination
      of Cd by chelating.

PMID- 26215157
TI  - Autoimmune hemolytic anemia associated with renal urothelial cancer: A case
      report and literature review.
AB  - BACKGROUND: Autoimmune hemolytic anemia (AIHA) is hemolytic anemia characterized
      by autoantibodies directed against red blood cells. AIHA can be induced by
      hematological neoplasms such as malignant lymphoma, but is rarely observed in the
      urological field. We report a case of renal urothelial cancer inducing Coombs
      positive warm AIHA and severe thrombocytopenia that was responsive to
      nephroureterectomy. CASE PRESENTATION: A 52-year-old man presented with a 1-month
      history of general weakness and dizziness. Hemoglobin level was 4.2 g/dL, and
      direct and indirect Coombs tests both yielded positive results. Abdominal
      computed tomography revealed huge left hydronephrosis due to a renal pelvic tumor
      measuring 4.0 x 4.0 x 3.0 cm, and renal regional lymph-node involvement was also
      observed and suspected as metastasis. Corticosteroid therapy was administered,
      and nephroureterectomy was performed. After surgical resection, the hemoglobin
      level gradually normalized, and direct and indirect Coombs tests yielded negative
      results. We thus diagnosed warm AIHA associated with renal urothelial cancer.
      CONCLUSION: To the best of our knowledge, this represents the first report of
      AIHA associated with renal urothelial cancer and severe thrombocytopenia
      responsive to nephroureterectomy. Renal urothelial cancer needs to be included in
      the differential diagnoses for warm AIHA, and nephroureterectomy represents a
      treatment option for AIHA.

PMID- 26215158
TI  - Factors affecting the tissues composition of pork belly.
AB  - Bellies derived from the commercial population of pig carcasses are diverse in
      terms of tissue composition. Knowledge of the factors influencing it and the
      expected results, permits quick and easy evaluation of raw material. The study
      was designed to determine the factors affecting the tissues composition of pork
      bellies and to estimate their lean meat content. The research population (n=140
      pig carcasses) was divided into groups according to sex (gilts, barrows), half
      carcass mass (<40, 40 to 43.9, 44 to 46.9, ?47 kg) and lean meat content class: S
      (?60%), E (55% to 60%), U (50% to 55%), R (<50%). Bellies were subjected to a
      detailed dissection. Half-carcass mass affected the levels of all the analysed
      parameters. The only exception was the mass of the fat with the skin in the 40 to
      43.9 kg group, for which the value did not differ statistically between the two
      groups <40 and 44 to 46.9 kg. Decrease in lean meat content affected the growth
      of the fat and skin mass in a linear way. No differences were observed between
      class S and E in terms of belly muscle mass. A 0.37% higher share of belly in the
      half-carcass was found for barrows (P<0.001), although bellies issued from
      barrows were characterized by a higher proportion of fat with skin compared with
      gilts (P=0.02). Interactions were observed between sex and half-carcass mass, so
      the sex of heavy half-carcasses becomes an important determinant for conditioning
      the muscle content. Equations were calculated and allow a fast and highly
      accurate determination of the lean meat content in bellies, suggesting they may
      be used directly in the production line. 

PMID- 26215159
TI  - Responsive hairpin DNA aptamer switch to program the strand displacement reaction
      for the enhanced electrochemical assay of ATP.
AB  - A responsive hairpin DNA aptamer switch was ingeniously designed for enzyme-free,
      sensitive and selective electrochemical detection of ATP. It takes full advantage
      of the target-triggered liberation effect of the toehold region and the
      concomitant proximity effect with the branch-migration region to execute the
      toehold-mediated strand displacement reaction on the electrode surface. 

PMID- 26215160
TI  - Effects of dietary extra virgin olive oil and its fractions on antioxidant status
      and DNA damage in the heart of rats co-exposed to aluminum and acrylamide.
AB  - Oxidative stress generated by an excessive production of free radicals has been
      linked to the development of several health problems such as cardiovascular
      diseases. We investigated the protective efficacy of Extra Virgin Olive Oil
      (EVOO) and its lipophilic fraction (OOLF) and hydrophilic fraction (OOHF) against
      the cardiotoxicity and DNA damage induced by co-exposure to aluminum (AlCl3) and
      acrylamide (ACR). Rats were divided into eight groups of six each: controls,
      AlCl3 (50 mg per kg body weight) administered via drinking water and ACR (20 mg
      per kg body weight) given by gavage, combined group plus EVOO (300 MUl); combined
      group plus the hydrophilic fraction (1 ml); combined group plus the lipophilic
      fraction (300 MUl); extra virgin olive oil (EVOO) and its fractions were
      administered daily by gavage for 21 days. Three other groups, considered as
      positive controls, received either EVOO, OOLF or OOLH. Exposure of rats to both
      AlCl3 and ACR provoked oxidative stress objectified by an increase in MDA, AOPP
      and a decrease in GSH, NPSH and vitamin C levels. The activities of CAT, GPx and
      SOD were also decreased. EVOO and its OOLF fraction exhibited a pronounced
      enhancement of antioxidant status while a partial recovery in the antioxidant
      status was obtained with the OOHF fraction. Plasma LDH and CK activities, TC, LDL
      C levels, TC/HDL-C and LDL-C/HDL-C ratios were increased, while HDL-C and TG
      decreased in rats treated with both AlCl3 and ACR. Co-administration of EVOO,
      OOLF or OOHF to treated rats restored cardiac biomarkers and lipid profile to
      near-normal values. Histological studies and DNA damage confirmed the biochemical
      parameters and the beneficial role of EVOO and its two fractions. Our results
      suggest that extra virgin olive oil and its two fractions can decrease the
      frequency of cardiac complications and genotoxicity. 

PMID- 26215162
TI  - Pressure-induced oligomerization of alanine at 25  degrees C.
AB  - Pressure-induced oligomerization was found from high-pressure experiments at 25 
      degrees C on alanine powder soaked in its saturated aqueous solution. The
      oligomerization to alanylalanine occurred at 5 GPa. The maximum yields of
      alanylalanine and trialanine were, respectively, 1.1 * 10(-3) and 1.3 * 10(-4) at
      11 GPa. 

PMID- 26215161
TI  - Kinetic discrimination of self/non-self RNA by the ATPase activity of RIG-I and
      MDA5.
AB  - BACKGROUND: The cytoplasmic RIG-like receptors are responsible for the early
      detection of viruses and other intracellular microbes by activating the innate
      immune response mediated by type I interferons (IFNs). RIG-I and MDA5 detect
      virus-specific RNA motifs with short 5'-tri/diphosphorylated, blunt-end double
      stranded RNA (dsRNA) and >0.5-2 kb long dsRNA as canonical agonists,
      respectively. However, in vitro, they can bind to many RNA species, while in
      cells there is an activation threshold. As SF2 helicase/ATPase family members,
      ATP hydrolysis is dependent on co-operative RNA and ATP binding. Whereas
      simultaneous ATP and cognate RNA binding is sufficient to activate RIG-I by
      releasing autoinhibition of the signaling domains, the physiological role of the
      ATPase activity of RIG-I and MDA5 remains controversial. RESULTS: A cross
      analysis of a rationally designed panel of RNA binding and ATPase mutants and
      truncated receptors, using type I IFN promoter activation as readout, allows us
      to refine our understanding of the structure-function relationships of RIG-I and
      MDA5. RNA activation of RIG-I depends on multiple critical RNA binding sites in
      its helicase domain as confirmed by functional evidence using novel mutations. We
      found that RIG-I or MDA5 mutants with low ATP hydrolysis activity exhibit
      constitutive activity but this was fully reverted when associated with mutations
      preventing RNA binding to the helicase domain. We propose that the turnover
      kinetics of the ATPase domain enables the discrimination of self/non-self RNA by
      both RIG-I and MDA5. Non-cognate, possibly self, RNA binding would lead to fast
      ATP turnover and RNA disassociation and thus insufficient time for the caspase
      activation and recruitment domains (CARDs) to promote downstream signaling,
      whereas tighter cognate RNA binding provides a longer time window for downstream
      events to be engaged. CONCLUSIONS: The exquisite fine-tuning of RIG-I and MDA5
      RNA-dependent ATPase activity coupled to CARD release allows a robust IFN
      response from a minor subset of non-self RNAs within a sea of cellular self RNAs.
      This avoids the eventuality of deleterious autoimmunity effects as have been
      recently described to arise from natural gain-of-function alleles of RIG-I and
      MDA5.

PMID- 26215164
TI  - "Are Your Clients Having Fun?" The Implications of Respondents' Preferences for
      the Delivery of Group Exercise Programs for Falls Prevention.
AB  - BACKGROUND: Group exercise has been shown to be effective in preventing falls;
      however, adherence to these interventions is often poor. Older adults'
      preferences for how these programs can be delivered are unknown. OBJECTIVE: To
      identify older people's preferences for how group exercise programs for falls
      prevention can be delivered. DESIGN: A two-wave, cross-sectional, state-wide
      telephone survey was undertaken. Respondents were community-dwelling men and
      women aged 70+ in Victoria, Australia. METHODS: Open-ended questions were asked
      to elicit information regarding respondent preferences of the program, which were
      analyzed using a framework approach. RESULTS: Ninety-seven respondents completed
      the follow-up survey. The results indicate that older adults most frequently
      report the short-term advantages and disadvantages when describing their
      preferences for group exercise, such as enjoyment, social interaction, and leader
      qualities. Longer-term advantages such as falls prevention were described less
      frequently. CONCLUSIONS: This study indicates the importance of interpersonal
      skills, and that the opportunity for social interaction should not be overlooked
      as a positive feature of a group exercise program.

PMID- 26215163
TI  - Key innovation or adaptive change? A test of leaf traits using Triodiinae in
      Australia.
AB  - The evolution of novel traits ("key innovations") allows some lineages to move
      into new environments or adapt to changing climates, whereas other lineages may
      track suitable habitat or go extinct. We test whether, and how, trait shifts are
      linked to environmental change using Triodiinae, C4 grasses that form the
      dominant understory over about 30% of Australia. Using phylogenetic and relaxed
      molecular clock estimates, we assess the Australian biogeographic origins of
      Triodiinae and reconstruct the evolution of stomatal and vascular bundle
      positioning. Triodiinae diversified from the mid-Miocene, coincident with the
      aridification of Australia. Subsequent niche shifts have been mostly from the
      Eremaean biome to the savannah, coincident with the expansion of the latter.
      Biome shifts are correlated with changes in leaf anatomy and radiations within
      Triodiinae are largely regional. Symplectrodia and Monodia are nested within
      Triodia. Rather than enabling biome shifts, convergent changes in leaf anatomy
      have probably occurred after taxa moved into the savannah biome-they are likely
      to have been subsequent adaptions rather than key innovations. Our study
      highlights the importance of testing the timing and origin of traits assumed to
      be phenotypic innovations that enabled ecological shifts. 

PMID- 26215165
TI  - Observation of optical solitons in PT-symmetric lattices.
AB  - Controlling light transport in nonlinear active environments is a topic of
      considerable interest in the field of optics. In such complex arrangements, of
      particular importance is to devise strategies to subdue chaotic behaviour even in
      the presence of gain/loss and nonlinearity, which often assume adversarial roles.
      Quite recently, notions of parity-time (PT) symmetry have been suggested in
      photonic settings as a means to enforce stable energy flow in platforms that
      simultaneously employ both amplification and attenuation. Here we report the
      experimental observation of optical solitons in PT-symmetric lattices. Unlike
      other non-conservative nonlinear arrangements where self-trapped states appear as
      fixed points in the parameter space of the governing equations, discrete PT
      solitons form a continuous parametric family of solutions. The possibility of
      synthesizing PT-symmetric saturable absorbers, where a nonlinear wave finds a
      lossless path through an otherwise absorptive system is also demonstrated. 

PMID- 26215168
TI  - High-throughput HPLC-MS/MS determination of the persistence of neonicotinoid
      insecticide residues of regulatory interest in dietary bee pollen.
AB  - The aim of this work is the development of a simple, fast, quantitative, and
      economic method for the determination of neonicotinoid insecticide residues in
      dietary bee pollen. Several parameters of the method, such as extraction solvent,
      extraction time, and solid-phase extraction sorbents for purification [silica,
      C18, primary-secondary amine (PSA), and Envi-Carb II/PSA], were studied. The
      final proposed method based on solid-liquid extraction with hexane, cleanup with
      SupelcleanTM Envi-Carb II/PSA cartridges, and subsequent analysis by high
      performance liquid chromatography with tandem mass spectrometry was validated and
      applied to the analysis of commercial bee pollen samples from different
      geographical zones. Method performance was assessed by the evaluation of several
      quality parameters of the method, such as recovery values, repeatability,
      reproducibility, linearity, and limits of detection and quantification. Matrix
      effects on the chromatographic signal were also studied. The quality parameters
      of the method were equivalent to or better than those obtained with previously
      published methods, with recoveries between 81 and 99% and repeatabilities lower
      than 8.8%. The detection and quantification limits were in the ranges 0.2-2.2 MUg
      kg(-1) and 0.4-4.3 MUg kg(-1), respectively.

PMID- 26215167
TI  - Community Trial of a Faith-Based Lifestyle Intervention to Prevent Diabetes Among
      African-Americans.
AB  - About 75% of African-Americans (AAs) ages 20 or older are overweight and nearly
      50% are obese, but community-based programs to reduce diabetes risk in AAs are
      rare. Our objective was to reduce weight and fasting plasma glucose (FPG) and
      increase physical activity (PA) from baseline to week-12 and to month-12 among
      overweight AA parishioners through a faith-based adaptation of the Diabetes
      Prevention Program called Fit Body and Soul (FBAS). We conducted a single
      blinded, cluster randomized, community trial in 20 AA churches enrolling 604 AAs,
      aged 20-64 years with BMI >= 25 kg/m(2) and without diabetes. The church (and
      their parishioners) was randomized to FBAS or health education (HE). FBAS
      participants had a significant difference in adjusted weight loss compared with
      those in HE (2.62 vs. 0.50 kg, p = 0.001) at 12-weeks and (2.39 vs. -0.465 kg, p
      = 0.005) at 12-months and were more likely (13%) than HE participants (3%) to
      achieve a 7% weight loss (p < 0.001) at 12-weeks and a 7% weight loss (19 vs. 8%,
      p < 0.001) at 12-months. There were no significant differences in FPG and PA
      between arms. Of the 15.2% of participants with baseline pre-diabetes, those in
      FBAS had, however, a significant decline in FPG (10.93 mg/dl) at 12-weeks
      compared with the 4.22 mg/dl increase in HE (p = 0.017), and these differences
      became larger at 12-months (FBAS, 12.38 mg/dl decrease; HE, 4.44 mg/dl increase)
      (p = 0.021). Our faith-based adaptation of the DPP led to a significant reduction
      in weight overall and in FPG among pre-diabetes participants. CLINICALTRIALS. GOV
      IDENTIFIER: NCT01730196.

PMID- 26215169
TI  - Probing the kinetics of quantum dot-based proteolytic sensors.
AB  - As an enzyme superfamily, proteases are rivaled only by kinases in terms of their
      abundance within the human genome. Two ratiometric quantum dot (QD) Forster
      resonance energy transfer-based sensors designed to monitor the activity of the
      proteolytic enzymes collagenase and elastase are investigated here. Given the
      unique material constraints of these sensing constructs, assays are realized
      utilizing excess enzyme and fixed substrate in progress curve format to yield
      enzyme specificity or k cat/K m ratios. The range of k cat/Km values derived is
      0.5-1.1 mM(-1) s(-1) for the collagenase sensor and 3.7-4.2 mM(-1) s(-1) for the
      elastase sensor. Of greater interest is the observation that the elastase sensor
      can be well represented by the Michaelis-Menten model while the collagenase
      sensor cannot. The latter demonstrates increased specificity at higher peptide
      substrate/QD loading values and an apparent QD-caused reversible inhibition as
      the reaction progresses. Understanding the detailed kinetic mechanisms that
      underpin these types of sensors will be important especially for their further
      quantitative utilization. 

PMID- 26215170
TI  - Analysis of IS6110 insertion sites provide a glimpse into genome evolution of
      Mycobacterium tuberculosis.
AB  - Insertion sequence (IS) 6110 is found at multiple sites in the Mycobacterium
      tuberculosis genome and displays a high degree of polymorphism with respect to
      copy number and insertion sites. Therefore, IS6110 is considered to be a useful
      molecular marker for diagnosis and strain typing of M. tuberculosis. Generally
      IS6110 elements are identified using experimental methods, useful for analysis of
      a limited number of isolates. Since short read genome sequences generated using
      next-generation sequencing (NGS) platforms are available for a large number of
      isolates, a computational pipeline for identification of IS6110 elements from
      these datasets was developed. This study shows results from analysis of NGS data
      of 1377 M. tuberculosis isolates. These isolates represent all seven major global
      lineages of M. tuberculosis. Lineage specific copy number patterns and
      preferential insertion regions were observed. Intra-lineage differences were
      further analyzed for identifying spoligotype specific variations. Copy number
      distribution and preferential locations of IS6110 in different lineages imply
      independent evolution of IS6110, governed mainly through ancestral insertion,
      fitness (gene truncation, promoter activity) and recombinational loss of some
      copies. A phylogenetic tree based on IS6110 insertion data of different isolates
      was constructed in order to understand genome level variations of different
      markers across different lineages. 

PMID- 26215171
TI  - [The development and validation of a standardised transfer sheet for care
      transitions between residential and acute care settings in Leuven, Belgium].
AB  - BACKGROUND: When elderly patients are transferred from a residential to an acute
      care setting, important information regarding their health care can be lost. Over
      the past years, the concept of advance care planning has also been given a more
      prominent place in the care for the elderly. However it remains a challenge to
      communicate the results achieved by this process when patients are referred to
      another health care setting. Developing a sound method for transferring
      information is a key element in the transitional care for the elderly patient.
      OBJECTIVES: In collaboration with the residential and acute care settings in
      Leuven, Flemish Brabant, Belgium this study aimed to develop a validated,
      standardized transfer-sheet. METHODS: After a literature search a topic list was
      generated to be used as the basis for a Delphi-procedure in which 16 experts from
      both the acute and the residential care settings participated. The transfer-sheet
      was then evaluated for content validity by an expert-panel (n = 9) from the acute
      and residential care settings. Face validity was assessed by two nurses and two
      doctors, randomly selected from the above settings. RESULTS: All 44 subthemes in
      the transfer-sheet showed excellent content validity. The scale content validity
      universal agreement (S CVIUA) for the entire transfer-sheet was 0.68. The average
      scale content validity (S CVIAve) was 0.96. After a second and final Delphi-round
      a final transfer-sheet was constructed consisting of 8 themes and 50 sub-themes.
      CONCLUSIONS: Based on these results standardized transfer-sheet was developed and
      validated.

PMID- 26215166
TI  - OX40, OX40L and Autoimmunity: a Comprehensive Review.
AB  - The tumour necrosis factor receptor OX40 (CD134) is activated by its cognate
      ligand OX40L (CD134L, CD252) and functions as a T cell co-stimulatory molecule.
      OX40-OX40L interactions have been proposed as a potential therapeutic target for
      treating autoimmunity. OX40 is expressed on activated T cells, and in the mouse
      at rest on regulatory T cells (Treg). OX40L is found on antigen-presenting cells,
      activated T cells and others including lymphoid tissue inducer cells, some
      endothelia and mast cells. Expression of both molecules is increased after
      antigen presentation occurs and also in response to multiple other pro
      inflammatory factors including CD28 ligation, CD40L ligation and interferon-gamma
      signaling. Their interactions promote T cell survival, promote an effector T cell
      phenotype, promote T cell memory, tend to reduce regulatory function, increase
      effector cytokine production and enhance cell mobility. In some circumstances,
      OX40 agonism may be associated with increased tolerance, although timing with
      respect to antigenic stimulus is important. Further, recent work has suggested
      that OX40L blockade may be more effective than OX40 blockade in reducing
      autoimmunity. This article reviews the expression of OX40 and OX40L in health,
      the effects of their interactions and insights from their under- or over
      expression. We then review OX40 and OX40L expression in human autoimmune disease,
      identified associations of variations in their genes (TNFRSF4 and TNFSF4,
      respectively) with autoimmunity, and data from animal models of human diseases. A
      rationale for blocking OX40-OX40L interaction in human autoimmunity is then
      presented along with commentary on the one trial of OX40L blockade in human
      disease conducted to date. Finally, we discuss potential problems with clinical
      use of OX40-OX40L directed pharmacotherapy. 

PMID- 26215172
TI  - Postexercise autonomic function after repeated-sprints training.
AB  - PURPOSE: We examined the effects of an 8-week repeated-sprint (RS) training
      protocol on postexercise parasympathetic reactivation (PNSr) in healthy adults.
      METHODS: Eighteen male adults (24.3 +/- 3.7 years) were assigned to either of two
      groups. One group (n = 9) performed RS training (EXP, 3 times week(-1), 18
      maximal all-out 15-m sprints interspersed with 17 s of passive recovery); the
      other served as the control group (CON, n = 9). Performance before, during, and
      after was assessed by measuring RS ability time (S dec) and total sprint time.
      The subjects were then seated for 10 min immediately after each trial and
      postexercise HR recovery (HRR), and vagal-related HR variability (HRV) indices
      were measured. RESULTS: All subjects demonstrated a decrease in S dec. However,
      only EXP showed a decrease in total sprint time (-10.5 % of baseline value).
      Using a qualitative statistical analysis method, we found a likely to almost
      certain positive effect of RS training on HR. The mean of each HRR and HRV index
      indicated a greater change in PNSr in EXP than in CON (e.g. with a 78/22/1 %
      chance to demonstrate a positive/trivial/negative effect on HRR60s after RS
      training; 74/21/5 % on LN rMSSD5-10min). Large correlations were noted between
      the changes in S dec [r = 0.59, 90 % CI (0.43)], total sprint time [r = -0.61
      (0.42)] and HRR60s. CONCLUSION: RS training seems to be an effective method to
      improve postexercise PNSr in healthy adults. Also, HRR60s appears to be a method
      for evaluating positive adaption to RS training.

PMID- 26215174
TI  - EUROSPINE 2015 Copenhagen, Denmark, September 2 - 4 : QUICK FIRES (Concurrent
      Short 7 Communications).

PMID- 26215175
TI  - EUROSPINE 2015 Copenhagen, Denmark, September 2 - 4 : POSTER PRESENTATIONS.

PMID- 26215173
TI  - Negative Affect and Child Internalizing Symptoms: The Mediating Role of
      Perfectionism.
AB  - Separate lines of research have linked the temperament factor negative affect and
      perfectionism with internalizing disorders. Despite theory, no previous studies
      have connected these lines of research to examine internalizing pathology. The
      current study tested a path model to investigate the mediating effect of
      perfectionism domains on the relation between negative affect and child anxiety,
      worry, and depression symptoms. Participants were 61 parent-child dyads recruited
      from the community. Children were 7-13 years old (54.1 % male; 88.2 % Caucasian).
      Overall the model fit the data well. Analyses indicated that separate domains of
      perfectionism mediated separate relations between negative affect and child
      anxiety, worry, and depression symptoms. The findings suggest that domains of
      perfectionism may be implicated in specific paths between negative affect and
      child anxiety, depression, and worry. Implications and future directions are
      discussed. 

PMID- 26215176
TI  - Subarachnoidal pleural fistula after resection of intradural thoracic disc
      herniation and multimodal treatment with noninvasive positive pressure
      ventilation (NPPV).
AB  - Subarachnoid pleural fistula (SPF) is a type of cerebrospinal fluid (CSF) fistula
      that can arise as a complication following transthoracic resection of
      intervertebral disc herniation in the thoracic spine. It is an abnormal
      communication between the subarachnoid and pleural space. Negative intrapleural
      pressure promotes CSF leak due to a suction effect into the pleural cavity, with
      little chance of spontaneous closure. Due to the risk of severe complications
      with CSF leak into the thoracic cavity, early diagnosis and treatment are
      mandatory. However, management can be challenging. We report a case of a 72-year
      old woman who underwent anterior thoracic surgery to treat thoracic myelopathy
      caused by an ossified intradural disc herniation. The postoperative period was
      complicated by a subarachnoidal pleural fistula. We describe our successful
      treatment of this using noninvasive positive pressure ventilation and lumbar CSF
      drainage and review other methods reported in the literature. 

PMID- 26215177
TI  - Duration-dependent influence of dynamic torsion on the intervertebral disc: an
      intact disc organ culture study.
AB  - PURPOSE: Mechanical loading is an important parameter that alters the homeostasis
      of the intervertebral disc (IVD). Studies have demonstrated the role of
      compression in altering the cellular metabolism, anabolic and catabolic events of
      the disc, but little is known how complex loading such as torsion-compression
      affects the IVD cell metabolism and matrix homeostasis. Studying how the duration
      of torsion affects disc matrix turnover could provide guidelines to prevent
      overuse injury to the disc and suggest possible beneficial effect of torsion. The
      aim of the study was to evaluate the biological response of the IVD to different
      durations of torsional loading. METHODS: Intact bovine caudal IVD were isolated
      for organ culture in a bioreactor. Different daily durations of torsion were
      applied over 7 days at a physiological magnitude (+/-2 degrees ) in combination
      with 0.2 MPa compression, at a frequency of 1 Hz. RESULTS: Nucleus pulpous (NP)
      cell viability and total disc volume decreased with 8 h of torsion-compression
      per day. Gene expression analysis suggested a down-regulated MMP13 with increased
      time of torsion. 1 and 4 h per day torsion-compression tended to increase the
      glycosaminoglycans/hydroxyproline ratio in the NP tissue group. CONCLUSIONS: Our
      result suggests that load duration thresholds exist in both torsion and
      compression with an optimal load duration capable of promoting matrix synthesis
      and overloading can be harmful to disc cells. Future research is required to
      evaluate the specific mechanisms for these observed effects.

PMID- 26215178
TI  - Expert's comment concerning Grand Rounds case entitled "Subarachnoidal pleural
      fistula after resection of intradural thoracic disc herniation and multimodal
      treatment with noninvasive positive pressure ventilation (NPPV)" (H. R. Schlag,
      S. Muquit, T. B. Hristov, G. Morassi, B. M. Boszczyk, M. Shafafy).

PMID- 26215179
TI  - The Impact of Modic-2 changes on the clinical outcomes of single-level anterior
      cervical discectomy and fusion.
AB  - PURPOSE: The purpose of the study was to explore the impact of Modic-2 changes on
      the clinical outcomes of single-level anterior cervical discectomy and fusion.
      METHODS: This study retrospectively reviewed the medical records of 35 ACDF
      patients with Modic-2 changes at adjacent level (Group A) and 213 patients
      without Modic-2 changes at adjacent level (Group B). Clinical and radiographic
      evaluations were performed preoperatively and repeated at 3, 6, 12, and 60 months
      after surgery. RESULT: All patients were followed up for an average of 60 months.
      The clinical improvements in terms of NDI and JOA scores were achieved in both
      groups (P < 0.05), and no significant differences were found between the two
      groups (P > 0.05). The radiologic review demonstrated ASD was proven in 9
      patients in Group A and 52 patients in Group B. A significant increase in ROM at
      the adjacent segments after surgery was observed in both groups (P < 0.05). No
      significant differences in adjacent segment ROM and DH were observed between two
      groups (P > 0.05). Comparing the outcome VAS of axial symptoms with Group A after
      surgery, patients in the Group B reported significantly lower VAS of axial
      symptoms at 1-year follow-up (P < 0.05). There were no significant differences
      between the two groups at the final follow-up (P > 0.05). CONCLUSION: Modic-2
      changes at adjacent level at baseline does not affect fusion rate or clinical
      outcome based on functional status but could negatively impact axial symptoms
      intensity and ASD, compared to patients without Modic-2 changes.

PMID- 26215180
TI  - Predictors of long-term stability of maxillary dental arch dimensions in patients
      treated with a transpalatal arch followed by fixed appliances.
AB  - BACKGROUND: The aim of this retrospective study was to identify which dental
      and/or cephalometric variables were predictors of long-term maxillary dental arch
      stability in patients treated with a transpalatal arch (TPA) during the mixed
      dentition phase followed by full fixed appliances in the permanent dentition.
      METHODS: Thirty-six patients, treated with TPA followed up by full fixed
      appliances, were divided into stable and relapse groups based on the long-term
      presence or not of relapse. Intercuspid, interpremolar and intermolar widths,
      arch length and perimeter, crowding, and upper incisor proclination were
      evaluated before treatment (T 0), post-TPA treatment (T 1), post-fixed appliance
      treatment (T 2), and a minimum of 3 years after full fixed appliances' removal (T
      3). A binary logistic regression was performed thereafter to evaluate the impact
      of the dental arch and cephalometric measurements at T 1 and the changes between
      T 0 and T 1 as predictive variables for relapse at T 3. RESULTS: The proposed
      model explained 42.7 % of the variance in treatment stability and correctly
      classified 72.2 % of the sample. Of the seven predictive variables, only upper
      anterior crowding (p = 0.029) was statistically significant. For every millimeter
      of decreased crowding at T 1 (after TPA treatment/before starting the fixed
      orthodontic treatment), there was an increase of 3.57 times in the odds of having
      stability. CONCLUSIONS: The best predictor of relapse was maxillary crowding
      before treatment. The odds of relapse increase by 3.6 times for every millimeter
      of crowding at baseline.

PMID- 26215181
TI  - The report of sequence analysis on familial Mediterranean fever gene (MEFV) in
      South-eastern Mediterranean region (Kahramanmaras) of Turkey.
AB  - Familial Mediterranean fever (FMF) is defined as an inherited and autosomal
      recessive disease. Many researches have been done about this subject, and we
      believe that it should be necessary to focus on phenotype-genotype correlation,
      especially novel mutation types. We aim to announce the results of FMF sequence
      analysis in Kahramanmaras/Turkey. The number of participants is 380 males and 451
      females who clinically diagnosed as FMF subjects of different age groups. Genomic
      sequences of exons 2 and 10 and in some cases exon 3 of the MEFV gene were
      scanned for mutations by sequence analyzer. The most common mutation identified
      in 230 (57.07 %) patients is heterozygous. The frequencies of mutation types in
      heterozygous subjects are R202Q (39.13 %), E148Q (18.70 %), M680I (16.52 %),
      M694V (13.91 %), and V726A (4.78 %), respectively. The most striking point among
      the compound heterozygous subjects is R202Q/M694V mutation type found at the
      highest rate (32 subjects). Fever and peritonitis are the most frequent signs of
      homozygous M694V and combine heterozygous mutations. Interestingly, the rate of
      homozygous mutation types (M694V/M694V+ R202Q/R202Q) is 96.70 % among all
      compound homozygous mutation types. The most frequent rate of homozygous patients
      is M680I mutation types (68.42 % in all homozygous mutation types). Two novel
      mutations were found in this study: N206K (p.Asn206Lys) and S208T (p.Ser208Tyr).
      Our findings in this study on the FMF sequence analysis are different from the
      results obtained from the other regions of Turkey.

PMID- 26215183
TI  - Validation of QTL for resistance to Aphanomyces euteiches in different pea
      genetic backgrounds using near-isogenic lines.
AB  - KEY MESSAGE: Marker-assisted backcrossing was used to generate pea NILs carrying
      individual or combined resistance alleles at main Aphanomyces resistance QTL. The
      effects of several QTL were successfully validated depending on genetic
      backgrounds. Quantitative trait loci (QTL) validation is an important and often
      overlooked step before subsequent research in QTL cloning or marker-assisted
      breeding for disease resistance in plants. Validation of QTL controlling partial
      resistance to Aphanomyces root rot, one of the most damaging diseases of pea
      worldwide, is of major interest for the future development of resistant
      varieties. The aim of this study was to validate, in different genetic
      backgrounds, the effects of various resistance alleles at seven main resistance
      QTL recently identified. Five backcross-assisted selection programs were
      developed. In each, resistance alleles at one to three of the seven main
      Aphanomyces resistance QTL were transferred into three genetic backgrounds,
      including two agronomically important spring (Eden) and winter (Isard) pea
      cultivars. The subsequent near-isogenic lines (NILs) were evaluated for
      resistance to two reference strains of the main A. euteiches pathotypes under
      controlled conditions. The NILs carrying resistance alleles at the major-effect
      QTL Ae-Ps4.5 and Ae-Ps7.6, either individually or in combination with resistance
      alleles at other QTL, showed significantly reduced disease severity compared to
      NILs without resistance alleles. Resistance alleles at some minor-effect QTL,
      especially Ae-Ps2.2 and Ae-Ps5.1, were also validated for their individual or
      combined effects on resistance. QTL * genetic background interactions were
      observed, mainly for QTL Ae-Ps7.6, the effect of which increased in the winter
      cultivar Isard. The pea NILs are a novel and valuable resource for further
      understanding the mechanisms underlying QTL and their integration in breeding
      programs.

PMID- 26215182
TI  - The influence of host genetics on erythrocytes and malaria infection: is there
      therapeutic potential?
AB  - As parasites, Plasmodium species depend upon their host for survival. During the
      blood stage of their life-cycle parasites invade and reside within erythrocytes,
      commandeering host proteins and resources towards their own ends, and
      dramatically transforming the host cell. Parasites aptly avoid immune detection
      by minimizing the exposure of parasite proteins and removing themselves from
      circulation through cytoadherence. Erythrocytic disorders brought on by host
      genetic mutations can interfere with one or more of these processes, thereby
      providing a measure of protection against malaria to the host. This review
      summarizes recent findings regarding the mechanistic aspects of this protection,
      as mediated through the parasites interaction with abnormal erythrocytes. These
      novel findings include the reliance of the parasite on the host enzyme
      ferrochelatase, and the discovery of basigin and CD55 as obligate erythrocyte
      receptors for parasite invasion. The elucidation of these naturally occurring
      malaria resistance mechanisms is increasing the understanding of the host
      parasite interaction, and as discussed below, is providing new insights into the
      development of therapies to prevent this disease.

PMID- 26215184
TI  - Identification of candidate genes associated with fertility restoration of
      cytoplasmic male-sterility in onion (Allium cepa L.) using a combination of
      bulked segregant analysis and RNA-seq.
AB  - KEY MESSAGE: A combination of BSA and RNA-seq was performed to identify
      candidates for the restorer-of-fertility gene in onion. The AcPMS1 involved in
      DNA mismatch repair was identified as the best candidate. To identify candidate
      genes of the restorer-of-fertility gene (Ms) responsible for fertility
      restoration of onion cytoplasmic male-sterility, a combined approach of bulked
      segregant analysis and RNA-seq was employed. From 32,674 de novo assembled
      contigs, 430 perfectly homozygous SNPs between male-fertile (MF) and male-sterile
      (MS) bulks were identified in 141 contigs. After verifying the homozygosity of
      the SNPs by PCR amplification and sequencing, the SNPs on 139 of the contigs were
      genotypes for the two recombinants which contained crossover events between the
      Ms locus and two tightly linked molecular markers. As a result, 30 contigs
      showing perfect linkage with the Ms locus in the large-sized segregating
      population were identified. Among them, 14 showed perfect linkage disequilibrium
      (LD) with the Ms locus, as determined by genotyping 251 domestic breeding lines.
      Furthermore, molecular markers tagging the 14 contigs also showed almost perfect
      LD with each other in 124 exotic accessions introduced from 21 countries, except
      for one accession which contained a crossover event by which the 14 markers were
      divided into two groups. After sequencing of the full-length cDNA of the 14
      contigs showing perfect LD, the deduced amino acids sequences of the MF and MS
      alleles were compared. Four genes were shown to harbor putative critical amino
      acid changes in the known domains. Among them, the gene encoding PMS1, involved
      in the DNA mismatch repair pathway, was assumed to be the best candidate gene
      responsible for fertility restoration of male-sterility in onion.

PMID- 26215185
TI  - Are area-based initiatives able to improve area safety in deprived areas? A quasi
      experimental evaluation of the Dutch District Approach.
AB  - BACKGROUND: Numerous area-based initiatives have been implemented in deprived
      areas across Western-Europe with the aim to improve the socio-economic and
      environmental conditions in these areas. Only few of these initiatives have been
      scientifically evaluated for their impact on key social determinants of health,
      like perceived area safety. Therefore, this study aimed to assess the impact of a
      Dutch area-based initiative called the District Approach on trends in perceived
      area safety and underlying problems in deprived target districts. METHODS: A
      quasi-experimental design was used. Repeated cross-sectional data on perceived
      area safety and underlying problems were obtained from the National Safety
      Monitor (2005-2008) and its successor the Integrated Safety Monitor (2008-2011).
      Study population consisted of 133,522 Dutch adults, including 3,595 adults from
      target districts. Multilevel logistic regression analyses were performed to
      assess trends in self-reported general safety, physical order, social order, and
      non-victimization before and after the start of the District Approach mid-2008.
      Trends in target districts were compared with trends in various control groups.
      RESULTS: Residents of target districts felt less safe, perceived less physical
      and social order, and were victimized more often than adults elsewhere in the
      Netherlands. For non-victimization, target districts showed a somewhat more
      positive change in trend after the start of the District Approach than the rest
      of the Netherlands or other deprived districts. Differences were only
      statistically significant in women, older adults, and lower educated adults. For
      general safety, physical order, and social order, there were no differences in
      trend change between target districts and control groups. CONCLUSIONS: Results
      suggest that the District Approach has been unable to improve perceptions of area
      safety and disorder in deprived areas, but that it did result in declining
      victimization rates.

PMID- 26215186
TI  - Self-harm in young people: Prevalence, associated factors, and help-seeking in
      school-going adolescents.
AB  - Adolescent self-harm is recognized as a serious public health problem; however,
      there is little reliable comparative data on its prevalence or characteristics,
      or on the extent of help-seeking for self-harm. The aims of the present study
      were to determine the prevalence and associated factors of adolescent self-harm
      in an urban region in Ireland, and to investigate help-seeking behaviours for
      self-harm. This was a cross-sectional study of 856 school-going adolescents,
      employing an anonymous self-report questionnaire. A lifetime history of self-harm
      was reported by 12.1% of adolescents. Factors independently associated with self
      harm included exposure to self-harm of a friend/family member. Professional help
      seeking was uncommon prior to (9%) and after (12%) self-harm. Furthermore, only
      6.9% of adolescents presented to hospital as a result of their last self-harm
      act. These findings indicate that self-harm is common in adolescents; however,
      seeking professional help is not a common phenomenon, and those who present to
      hospital represent the 'tip of the iceberg' of adolescent self-harm. Identifying
      the prevalence of self-harm and associated factors, in addition to help-seeking
      behaviours, in young people is important to determine the preventative programmes
      to target 'at-risk' groups. Mental health nurses have an important and increasing
      role to play in such school-based initiatives. 

PMID- 26215187
TI  - Development and evaluation of a specifically designed website for haematopoietic
      stem cell transplant patients in Leeds.
AB  - The purpose of this project was to develop and evaluate a specifically designed
      website (ALLograft INformation EXchange - ALLINEX) for adult allogeneic
      haematopoietic stem cell transplant (allo-HSCT) patients in Leeds. Specifications
      included information on the transplant journey and supportive care services,
      discussion forum and patient-clinical team electronic messaging service. The
      method followed a participatory action research approach in a five-phase project
      involving stakeholders. Phase 1 involved information gathering; Phase 2
      development of content; Phase 3 building of website and usability testing; Phase
      4 preliminary evaluation; and Phase 5 clinical implementation. Results concluded
      that Phase 1 patients were unaware of all services and reported unmet needs; gaps
      in support services were identified from a service evaluation; Phase 2 content
      was collected from experts, collated and synthesised; Phase 3 patient and staff
      feedback was positive and constructive resulting in more than 50 changes; Phase 4
      ALLINEX evaluation demonstrated acceptable usability with good layout, content
      and aesthetics reported; Phase 5, over 15 weeks, ALLINEX had 6630 page hits, 9
      new forum topics posted and received 3 clinical messages. The clinical team
      embraced responsibility for reviewing and monitoring ALLINEX. Financial and
      indemnity cover was secured for 3 years. ALLINEX, adopted locally, is sustainable
      and has functionality to roll-out to other UK allo-HSCT centres. 

PMID- 26215188
TI  - Reusable Inorganic Templates for Electrostatic Self-Assembly of Individual
      Quantum Dots, Nanodiamonds, and Lanthanide-Doped Nanoparticles.
AB  - In this paper, we present an electrostatic self-assembly method for the
      controlled placement of individual nanoparticle emitters based on reusable
      inorganic templates. This method can be used to integrate quantum emitters into
      nanophotonic structures over macroscopic areas and is applicable to a variety of
      patterning materials and emitter systems. By utilizing surface-charge-mediated
      self-assembly, highly ordered arrays of nanoparticle emitters were created. To
      illustrate the broad applicability of this technique, we demonstrate self
      assembly using colloidal quantum dots (QD), nitrogen vacancy (NV) centers in
      diamond nanoparticles, and lanthanide-doped upconversion nanoparticles (UCNP).
      Placement of single QDs and NV centers was confirmed by performing photon
      antibunching measurements using a Hanbury-Brown Twiss setup. In addition,
      template reusability was demonstrated through daily redeposition experiments over
      a one month period. 

PMID- 26215189
TI  - Gene-Expression-Based Predictors for Breast Cancer.
AB  - An important and often complicated management decision in early stage hormone
      receptor (HR)-positive breast cancer relates to the use of adjuvant systemic
      chemotherapy. Although traditional clinicopathologic markers exist, tremendous
      progress has been achieved in the field of predictive biomarkers and genomics
      with both prognostic and predictive capabilities to identify patients who will
      potentially benefit from additional therapy. The use of these genomic tests in
      the neoadjuvant setting is also being studied and may lead to these tests
      providing clinical benefit even earlier in the disease course. Landmark articles
      published in the last few years have expanded our knowledge of breast cancer
      genomics to an unprecedented level, and mutational analysis via next-generation
      sequencing methods allows the identification of molecular targets for novel
      targeted therapeutic agents and clinical trials testing efficacy of targeted
      therapies, such as PI3K inhibitors, in addition to endocrine therapy for HR
      positive breast cancer, are ongoing. We provide an in-depth review on the role of
      gene expression-based predictors in early stage breast cancer and an overview of
      future directions, including next-generation sequencing. Over the coming years,
      we anticipate a significant increase in utilization of genomic-based predictors
      for individualized selection and duration of endocrine therapy with and without
      genotype-driven targeted therapy, and a major decrease in the use of
      chemotherapy, possibly even leading to a chemotherapy-free road for early stage
      HR-positive breast cancer. 

PMID- 26215191
TI  - Genetics, Genomics, and Pharmacogenomics.

PMID- 26215190
TI  - Practical Value of Molecular Pathology in Stage I-III Lung Cancer: Implications
      for the Clinical Surgeon.
AB  - Over a decade since the discovery of EGFR mutation, and 6 years since prospective
      clinical trial data proved that routine molecular pathology tests improve
      survival in stage IV lung cancer, there is still debate whether to test patients
      with earlier stages of disease (stage I-III). As discoveries of targeted drugs
      for stage IV patients accelerate-prompting routine testing for ALK, ROS1, RET,
      BRAF V600E, and HER2, among others-there is an argument that all lung cancers
      should be genotyped for the purpose of classification, regardless of stage of
      disease. The counterargument is that because targeted drugs have only been
      validated for use in stage IV disease, these molecular tests need only be
      conducted at the time of disease recurrence. This review will describe current,
      practical applications of molecular pathology testing in early stage lung cancer,
      focusing on the immediate diagnostic, prognostic, and therapeutic implications
      for individual patient management. Meanwhile, large-scale clinical trials are
      underway to test targeted drugs as adjuvant therapies in patients with early
      stage disease.

PMID- 26215192
TI  - Prognostic and Predictive Biomarkers in Colorectal Cancer: Implications for the
      Clinical Surgeon.
AB  - Colorectal cancer is a heterogeneous disease with a wide range of long-term
      outcomes and responses to treatment. Recent advances in the genetic and molecular
      characterization of tumors has yielded a set of prognostic and predictive
      biomarkers that aid the identification of patients at higher risk for disease
      recurrence and progression, and in some cases indicate the likelihood of response
      to a specific treatment. Increasingly, these biomarkers have become integral to
      the treatment algorithm for managing patients with colorectal cancer. Prognostic
      and predictive factors in colorectal cancer can broadly be categorized into
      treatment impact, clinicopathologic factors, and molecular markers. This review
      will focus primarily on molecular markers, which are foundational to the
      paradigmatic shift toward personalized cancer therapy. 

PMID- 26215193
TI  - Decreasing Recurrence Rates for Ductal Carcinoma In Situ: Analysis of 2996 Women
      Treated with Breast-Conserving Surgery Over 30 Years.
AB  - BACKGROUND: Randomized trials of radiation after breast-conserving surgery (BCS)
      for ductal carcinoma in situ (DCIS) found substantial rates of recurrence, with
      half of the recurrences being invasive. Decreasing local recurrence rates for
      invasive breast carcinoma have been observed and are largely attributed to
      improvements in systemic therapy. In this study, we examine recurrence rates
      after BCS for DCIS over 3 decades at one institution. METHODS: We retrospectively
      reviewed a prospectively maintained database of DCIS patients undergoing BCS from
      1978 to 2010. Cox proportional hazard models were used to investigate the
      association between the treatment period and recurrence, controlling for other
      variables. RESULTS: Overall, 363 (12%) recurrences among 2996 cases were
      observed. Median follow-up for patients without recurrence was 75 months (range 0
      30 years); 732 patients were followed for >=10 years. The 5-year recurrence rate
      for the period 1978-1998 was 13.6 versus 6.6% for the period 1999-2010 [hazard
      ratio (HR) 0.62, p < 0.0001]. Controlling for age, family history, presentation,
      nuclear grade, necrosis, number of excisions, margin status, radiation, and
      endocrine therapy, treatment period remained significantly associated with
      recurrence, with later years associated with a lower HR (0.74, p = 0.02) compared
      to earlier. After stratification by radiation use, association of recurrence with
      treatment period persisted in those treated without radiation (HR 0.62, p =
      0.003). CONCLUSIONS: Recurrence rates for DCIS have fallen over time, with
      increases in screen detection, negative margins, and use of adjuvant therapies
      only partially explaining this decrease. The unexplained decline persists in
      women not receiving radiation, suggesting it is not due to changes in radiation
      efficacy but may be due to improvements in radiologic detection and pathologic
      assessment.

PMID- 26215194
TI  - Negative Genetic Testing Does Not Deter Contralateral Prophylactic Mastectomy in
      Younger Patients with Greater Family Histories of Breast Cancer.
AB  - BACKGROUND: Increasing rates of contralateral prophylactic mastectomy (CPM)
      correlate with adoption of total skin-sparing mastectomy (TSSM). We aimed to
      characterize patients with unilateral breast cancer who underwent TSSM with CPM
      or without CPM (No CPM). METHODS: We reviewed all patients with unilateral breast
      cancer who underwent TSSM from 2006 to 2013. Trends in CPM and genetic testing
      were evaluated across time. Patient characteristics and complications were
      compared between CPM and No CPM groups. RESULTS: We identified 591 patients (293
      No CPM and 298 CPM) with median follow-up of 25 (interquartile range [IQR] 13-52)
      months. All patients with deleterious mutations and 58% of those who tested
      negative for mutations underwent CPM. In patients who tested negative for
      mutations, CPM was correlated with younger patient age, greater family history,
      and younger age of relatives diagnosed with breast/ovarian cancer. CPM was
      associated with an increased risk of superficial nipple necrosis (relative risk
      [RR] 2.1, 95% confidence interval [CI] 1.12-4.0), wound breakdown (RR 1.62, 95%
      CI 1.04-2.5), and infections requiring oral antibiotics (RR 1.59, 95% CI 1.16
      2.2). In patients with tissue expander/implant reconstruction, CPM was associated
      with an increased risk of implant exposure (RR 1.95, 95% CI 1.03-3.7) but did not
      affect the risk of implant loss (RR 0.91, 95% CI 0.56-1.48). CONCLUSIONS:
      Patients who choose CPM fit the profile of patients with higher risk of
      contralateral breast cancer (CBC), which may be due to polygenic risk factors
      that are currently under investigation. Physicians should address patients' fears
      of CBC, screening concerns, and the risk of complications when considering CPM.

PMID- 26215195
TI  - Rethinking the Local Therapy of Breast Cancer: Integration of Biology and
      Anatomy.
AB  - Local control has traditionally been considered a function of disease burden.
      Local control is now known to differ among biologic subtypes of breast cancer and
      is greatly improved with the use of systemic therapy. This offers opportunities
      for decreasing the morbidity of treatment and individualizing local therapy. The
      use of smaller margins in breast-conserving surgery and elimination of axillary
      dissection for some node-positive breast cancer patients are current examples of
      leveraging the benefits of systemic therapy to reduce surgery. Emerging evidence
      indicates that molecular profiling can identify patients at high and low risk for
      locoregional recurrence after surgery in a more accurate way than tumor burden,
      potentially allowing individualization of the use of postmastectomy and
      comprehensive node field irradiation. Future clinical trials should incorporate
      both disease burden and molecular profiling when examining treatment strategies. 

PMID- 26215196
TI  - The Importance of Applying ACOSOG Z0011 Criteria in the Axillary Management of
      Invasive Lobular Carcinoma: A Multi-institutional Cohort Study.
AB  - BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial
      led to a significant change in the management of patients with early stage breast
      cancer and limited sentinel lymph node (SLN) metastases. However, only 27
      patients with invasive lobular carcinoma (ILC) were randomized to the completion
      axillary lymph node dissection (ALND) arm. To assess the generalizability of the
      Z0011 trial, the primary aim of this study was to determine the risk of residual
      nodal burden (RNB) for ILC. METHODS: A multi-institutional cohort study was
      completed. RNB was determined for women of any age with an ILC and at least one
      positive SLN who underwent a primary breast procedure (lumpectomy or mastectomy)
      and both a SLN biopsy followed by a completion ALND between July 1, 1999, and
      June 30, 2009, at two large academic centers. RESULTS: A total of 59 patients (60
      ILCs) met the inclusion criteria. Although the overall RNB was 40%, it was
      significantly greater in the T3+ group compared to T1/T2 (87 vs. 24%,
      respectively, p < 0.0001). When comparing only ILCs that met all of the inclusion
      criteria for ACOSOG Z0011 (T1 or T2, 1 or 2 SLNs positive, no SLN extranodal
      extension, and breast conservation) to those ILCs that did not, the RNB was
      significantly greater in the latter (56 vs. 17 %; p < 0.003). CONCLUSIONS:
      Overall, the clinical practice changes that have occurred after publication of
      the ACOSOG Z0011 trial appear to be generalizable to ILCs within the inclusion
      criteria of the study.

PMID- 26215197
TI  - Contemporary Challenges in Genetic Testing for Breast Cancer: A Collaboration
      Opportunity for Genetic Counselors and Breast Surgeons.

PMID- 26215199
TI  - Defining a Valid Age Cutoff in Staging of Well-Differentiated Thyroid Cancer.
AB  - BACKGROUND: Age 45 years is used as a cutoff in the staging of well
      differentiated thyroid cancer (WDTC) as it represents the median age of most
      datasets. The aim of this study was to determine a statistically optimized age
      threshold using a large dataset of patients treated at a comprehensive cancer
      center. METHODS: Overall, 1807 patients with a median follow-up of 109 months
      were included in the study. Recursive partitioning was used to determine which
      American Joint Committee on Cancer (AJCC) variables were most predictive of
      disease-specific death, and whether a different cutoff for age would be found.
      From the resulting tree, a new age cutoff was picked and patients were restaged
      using this new cutoff. RESULTS: The 10-year disease-specific survival (DSS) by
      Union for International Cancer Control (AJCC/UICC) stage was 99.6, 100, 96, and
      81 % for stages I-IV, respectively. Using recursive partitioning, the presence of
      distant metastasis was the most powerful predictor of DSS. For M0 patients, age
      was the next most powerful predictor, with a cutoff of 56 years. For M1 patients,
      a cutoff at 54 years was most predictive. Having reviewed the analysis, age 55
      years was selected as a more robust age cutoff than 45 years. The 10-year DSS by
      new stage (using age 55 years as the cutoff) was 99.2, 98, 100, and 74 % for
      stages I-IV, respectively. CONCLUSION: A change in age cutoff in the AJCC/UICC
      staging for WDTC to 55 years would improve the accuracy of the system and
      appropriately prevent low-risk patients being overstaged and overtreated.

PMID- 26215198
TI  - Toolbox to Reduce Lumpectomy Reoperations and Improve Cosmetic Outcome in Breast
      Cancer Patients: The American Society of Breast Surgeons Consensus Conference.
AB  - BACKGROUND: Multiple recent reports have documented significant variability of
      reoperation rates after initial lumpectomy for breast cancer. To address this
      issue, a multidisciplinary consensus conference was convened during the American
      Society of Breast Surgeons 2015 annual meeting. METHODS: The conference mission
      statement was to "reduce the national reoperation rate in patients undergoing
      breast conserving surgery for cancer, without increasing mastectomy rates or
      adversely affecting cosmetic outcome, thereby improving value of care." The goal
      was to develop a toolbox of recommendations to reduce the variability of
      reoperation rates and improve cosmetic outcomes. Conference participants included
      providers from multiple disciplines involved with breast cancer care, as well as
      a patient representative. Updated systematic reviews of the literature and
      invited presentations were sent to participants in advance. After topic
      presentations, voting occurred for choice of tools, level of evidence, and
      strength of recommendation. RESULTS: The following tools were recommended with
      varied levels of evidence and strength of recommendation: compliance with the SSO
      ASTRO Margin Guideline; needle biopsy for diagnosis before surgical excision of
      breast cancer; full-field digital diagnostic mammography with ultrasound as
      needed; use of oncoplastic techniques; image-guided lesion localization; specimen
      imaging for nonpalpable cancers; use of specialized techniques for intraoperative
      management, including excisional cavity shave biopsies and intraoperative
      pathology assessment; formal pre- and postoperative planning strategies; and
      patient-reported outcome measurement. CONCLUSIONS: A practical approach to
      performance improvement was used by the American Society of Breast Surgeons to
      create a toolbox of options to reduce lumpectomy reoperations and improve
      cosmetic outcomes.

PMID- 26215200
TI  - Is There a Correlation Between Clinical Complete Response and Pathological
      Complete Response After Neoadjuvant Chemoradiotherapy for Esophageal Squamous
      Cell Cancer?
AB  - OBJECTIVE: The aim of this study was to investigate the correlation between
      clinical complete response (cCR) and pathologic complete response (pCR) after
      neoadjuvant chemoradiotherapy (CRT) for esophageal squamous cell cancer (ESCC).
      METHODS: Between May 2001 and April 2013, a total of 158 patients with thoracic
      ESCC treated with neoadjuvant CRT followed by surgery were analyzed. Of these
      patients, 31 had stage IIb disease and 127 had stage III disease. All patients
      received concurrent platinum-based chemotherapy with conformal radiotherapy (40
      Gy in 20 fractions, five fractions per week for 4 weeks). RESULTS: A total of 65
      patients (41.1 %) achieved pCR. Of 44 patients (27.8 %) who achieved cCR after
      neoadjuvant CRT, 32 (72.7 %) also achieved pCR. On the other hand, only 33 (28.9
      %) of 114 patients with non-cCR had pCR. The sensitivity, specificity, positive
      predictive value, and negative predictive value of cCR for predicting pCR was
      87.1, 49.2, 71.1, and 72.7 %, respectively. The median follow-up period was 28.9
      months, and overall survival (OS) for the entire group was 38.1 months. Patients
      who achieved cCR had significantly better 3-year OS than those with non-cCR (71.6
      % vs. 46.9 %; p = 0.012). CONCLUSIONS: Our results indicate that cCR after
      neoadjuvant CRT is significantly correlated with pCR and survival of patients
      with ESCC. Further studies are required to confirm the prognostic value of cCR
      after neoadjuvant CRT.

PMID- 26215201
TI  - Association Between Obesity and BRAFV600E Mutation Status in Patients with
      Papillary Thyroid Cancer.
AB  - BACKGROUND: The prevalence of papillary thyroid cancer (PTC) is thought to be
      related to obesity, which affects the prognosis for PTC patients. However, the
      mechanisms implicated in the relationship between obesity and PTC is a matter for
      debate. In this study, we aimed to gain insight into the relationship between
      obesity and the clinicopathological features of PTC, including the BRAFV600E
      mutation. METHODS: The medical records of 1121 PTC patients were reviewed and the
      relationships between anthropometric factors, biochemical parameters, and
      clinicopathological parameters, including BRAFV600E mutation status, were
      analyzed. RESULTS: Body mass index (BMI) showed a strong association with
      advanced TNM stage (p < 0.001) and BRAFV600E mutation status (p = 0.008). We also
      found that BRAFV600E (+) patients had a higher body weight (p = 0.024) and a
      higher BMI (p = 0.003) than patients with BRAFV600E (-) PTC. In addition,
      BRAFV600E (+) PTC patients had a significantly higher incidence of extrathyroidal
      extension (p = 0.025) and more advanced T, N, TNM stage (p < 0.001) than
      BRAFV600E (-) PTC patients. Consistent with this observation, female BRAFV600E
      (+) PTC patients had a higher BMI (p = 0.011) and more aggressive tumor behaviors
      than female BRAFV600E (-) PTC patients. In multivariate analysis, BMI was
      persistently associated with BRAFV600E mutation in the entire cohort (odds ratio
      [OR] 1.387; 95 % CI 1.036-1.859; p = 0.028) and in the female subcohort (OR
      1.221; 95 % CI 1.014-1.631; p = 0.046). CONCLUSION: The positive association
      between BMI and BRAFV600E supports the hypothesis that excessive bodyweight
      influences tumor progression.

PMID- 26215202
TI  - Identification of Patients with Intermediate Thickness Melanoma at Low Risk for
      Sentinel Lymph Node Positivity.
AB  - INTRODUCTION: Sentinel lymph node (SLN) biopsy is recommended for all patients
      with intermediate-thickness melanomas. We sought to identify such patients at low
      risk of SLN positivity. METHODS: All patients with intermediate-thickness
      melanomas (1.01-4 mm) undergoing SLN biopsy at a single institution from 1995
      2011 were included in this retrospective cohort study. Univariate and
      multivariate logistic regression determined factors associated with a low risk of
      SLN positivity. Classification and regression tree (CART) analysis was used to
      stratify groups based on risk of positivity. RESULTS: Of the 952 study patients,
      157 (16.5 %) had a positive SLN. In the multivariate analysis, thickness <1.5 mm
      (odds ratio [OR] 0.29), age >=60 (OR 0.69), present tumor-infiltrating
      lymphocytes (OR 0.60), absent lymphovascular invasion (OR 0.46), and absent
      satellitosis (OR 0.44) were significantly associated with a low risk of SLN
      positivity. CART analysis identified thickness of 1.5 mm as the primary cut point
      for risk of SLN metastasis. Patients with a thickness of <1.5 mm represented 36 %
      of the total cohort and had a SLN positivity rate of 6.6 % (95 % confidence
      interval 3.8-9.4 %). In patients with melanomas <1.5 mm in thickness, the
      presence of additional low risk factors identified 257 patients (75 % of patients
      with <1.5 mm melanomas) in which the rate of SLN positivity was <5 %.
      CONCLUSIONS: Despite a SLN positivity rate of 16.5 % overall, substantial
      heterogeneity of risk exists among patients with intermediate-thickness melanoma.
      Most patients with melanoma between 1.01 and 1.5 mm have a risk of SLN positivity
      similar to that in patients with thin melanomas.

PMID- 26215204
TI  - Photocatalytic Water Splitting with the Acridine Chromophore: A Computational
      Study.
AB  - The hydrogen-bonded acridine-water complex is considered as a model system for
      the exploration of photochemical reactions which can lead to the splitting of
      water into H(*) and OH(*) radicals. The vertical excitation energies of the
      lowest singlet and triplet excited states of the complex were calculated with the
      CASSCF/CASPT2 and ADC(2) ab initio electronic-structure methods. In addition to
      the well-known excited states of the acridine chromophore, excited states of
      charge-transfer character were identified, in which an electron is transferred
      from the p orbital of the H2O molecule to the pi* orbital of acridine. The low
      energy barriers which separate these reactive charge-transfer states from the
      spectroscopic states of the acridine-water complex have been characterized by the
      calculation of two-dimensional relaxed potential-energy surfaces as functions of
      the H atom-transfer coordinate and the donor (O)-acceptor (N) distance. When
      populated, these charge-transfer states drive the transfer of a proton from the
      water molecule to acridine, which results in the acridinyl-hydroxyl biradical.
      The same computational methods were employed to explore the photochemistry of the
      (N-hydrogenated) acridinyl radical. The latter possesses low-lying (about 3.0 eV)
      pipi* excited states with appreciable oscillator strengths in addition to a low
      lying dark pipi* excited state. The bound potential-energy functions of the pipi*
      excited states are predissociated by the potential-energy function of an excited
      state of pisigma* character which is repulsive with respect to the NH stretching
      coordinate. The dissociation threshold of the pisigma* state is about 2.7 eV and
      thus below the excitation energies of the bright pipi* states. The conical
      intersections of the pisigma* state with the pipi* excited states and with the
      electronic ground state provide a mechanism for the direct and fast
      photodetachment of the H atom from the acridinyl radical. These computational
      results indicate that the H2O molecule in the acidine-H2O complex can be
      dissociated into H(*) and OH(*) radicals by the absorption of two
      visible/ultraviolet photons. 

PMID- 26215203
TI  - Characterisation of cell-substrate interactions between Schwann cells and three
      dimensional fibrin hydrogels containing orientated nanofibre topographical cues.
AB  - The generation of complex three-dimensional bioengineered scaffolds that are
      capable of mimicking the molecular and topographical cues of the extracellular
      matrix found in native tissues is a field of expanding research. The systematic
      development of such scaffolds requires the characterisation of cell behaviour in
      response to the individual components of the scaffold. In the present
      investigation, we studied cell-substrate interactions between purified
      populations of Schwann cells and three-dimensional fibrin hydrogel scaffolds, in
      the presence or absence of multiple layers of highly orientated electrospun
      polycaprolactone nanofibres. Embedded Schwann cells remained viable within the
      fibrin hydrogel for up to 7 days (the longest time studied); however, cell
      behaviour in the hydrogel was somewhat different to that observed on the two
      dimensional fibrin substrate: Schwann cells failed to proliferate in the fibrin
      hydrogel, whereas cell numbers increased steadily on the two-dimensional fibrin
      substrate. Schwann cells within the fibrin hydrogel developed complex process
      branching patterns, but, when presented with orientated nanofibres, showed a
      strong tendency to redistribute themselves onto the nanofibres, where they
      extended long processes that followed the longitudinal orientation of the
      nanofibres. The process length along nanofibre-containing fibrin hydrogel reached
      near-maximal levels (for the present experimental conditions) as early as 1 day
      after culturing. The ability of this three-dimensional, extracellular matrix
      mimicking scaffold to support Schwann cell survival and provide topographical
      cues for rapid process extension suggest that it may be an appropriate device
      design for the bridging of experimental lesions of the peripheral nervous system.

PMID- 26215205
TI  - Radiological study of the anatomy of the keystone area of the nasal septum using
      computed tomography to aid septal surgery.
AB  - OBJECTIVES: An optimum septoplasty result may require complete detachment of the
      superior osseocartilaginous junction (OCJ), but this may lead to disruption of
      the keystone area with loss of nasal support and consequent supratip depression
      deformity. The aim of this study was to analyse normal keystone anatomy using CT
      scan images and to estimate the incidence of risk of supratip depression when
      completely detaching the OCJ. DESIGN: Retrospective study. SETTING: Tertiary
      referral centre. PARTICIPANTS: Adult patients who underwent CT paranasal sinuses
      prior to transsphenoidal hypophysectomy in a tertiary referral centre between
      2009 and 2013. MAIN OUTCOME MEASURES: Length of the keystone area. A length of <5
      mm and certain anatomical configurations were considered at risk of a supratip
      depression with complete detachment of the OCJ. RESULTS: CT scans of 91 patients
      were reviewed. The mean keystone length was 9.04 mm (range 0-23 mm). Twenty-nine
      (32%) cases were at risk of supratip depression. Relatively shorter nasal bones
      (nasal bone length: overall dorsal length <0.37) (n = 26) were associated with a
      shorter keystone area (P = 0.0051). CONCLUSIONS: Thirty-two per cent of patients
      have keystone anatomy on radiology predisposing them to supratip depression with
      complete detachment of the OCJ. Relatively shorter nasal bones were significantly
      associated with a shorter, higher risk keystone area. In cases with a high septal
      deviation undergoing a septoplasty, a preoperative CT enables the surgeon to
      assess the keystone area and determine whether it is safe to completely detach
      the OCJ.

PMID- 26215206
TI  - Effect of stroke volume variation-directed fluid management on blood loss during
      living-donor right hepatectomy: a randomised controlled study.
AB  - Reducing blood loss is beneficial in living liver donor hepatectomy. Although it
      has been suggested that maintaining a low central venous pressure is important,
      it is known that low stroke volume variation may be associated with increased
      blood loss. Therefore, we compared the effect on blood loss of 40 patients
      randomly assigned to a high stroke volume variation group (maintaining 10-20% of
      stroke volume variation) vs 38 patients in a control group (maintaining < 10%
      stroke volume variation) during living-donor right hepatectomy. Mean (SD) blood
      loss during donor hepatectomy was significantly lower in the high stroke volume
      variation group than in the control group: 476 (131) ml vs 836 (341) ml,
      respectively (p < 0.001). Blood pressure and peri-operative laboratory values did
      not differ between the two groups. However, in the high stroke volume variation
      group, central venous pressure values were also significantly lower. We were
      unable to disentangle the effects of stroke volume variation and central venous
      pressure, but our results confirm that the two together appear beneficial.

PMID- 26215207
TI  - Online processing of sentences containing noun modification in young children
      with high-functioning autism.
AB  - BACKGROUND: There is variability in the language of children with autism, even
      those who are high functioning. However, little is known about how they process
      language structures in real time, including how they handle potential ambiguity,
      and whether they follow referential constraints. Previous research with older
      autism spectrum disorder (ASD) participants has shown that these individuals can
      use context to access rapidly the meaning of ambiguous words. The severity of
      autism has also been shown to influence the speed in which children with ASD
      access lexical information. AIMS: To understand more about how children with ASD
      process language in real time (i.e., as it unfolds). The focus was the
      integration of information and use of referential constraints to identify a
      referent named in a sentence. METHODS & PROCEDURES: We used an eye-tracking task
      to compare performance between young, high-functioning children with autism (HFA)
      and children with typical development (TD). A large sample of 5-9-year-old
      children (mean age = 6;8 years), 48 with HFA and 56 with TD participated; all
      were attending mainstream schools. For each item participants were shown a
      display of four images that differed in two dimensions. Each sentence contained
      an adjective and noun that restricted the choice from four to two (the target and
      competitor), followed by a prepositional phrase (e.g., the blue square with
      dots); this added modifying information to provide a unique description of the
      target. We calculated looking time at the target, the competitor and the two
      distractors for each 200 ms time interval as children processed the sentence and
      looked at the display. Generalized estimating equations were used to carry out
      repeated-measures analyses on the proportion of looking time to target and
      competitor and time to fixate to target. OUTCOMES & RESULTS: Children in both
      groups (HFA and TD) looked at the target and competitor more than at the
      distractors following the adjective and noun and following the modifying
      information in the prepositional phrase more at the target. However, the HFA
      group was significantly slower in both phases and looked proportionally less at
      the target. Across the sample, IQ and language did not affect the results;
      however, age and attention had an impact. The older children showed an advantage
      in processing the information as did the children with higher attention scores.
      CONCLUSIONS & IMPLICATIONS: The HFA group took longer than the TD group to
      integrate the disambiguating information provided in the course of processing a
      sentence and integrate it with the visual information, indicating that for the
      ASD group incremental processing was not as advanced as for children with ASD,
      and they were less sensitive to referential conventions. Training for young
      children with ASD on the use of referential conventions and available contextual
      clues may be of benefit to them in understanding the language they hear.

PMID- 26215208
TI  - Clinical remission of pityriasis rubra pilaris with adalimumab in an adolescent
      patient.

PMID- 26215210
TI  - Photoaging Mobile Apps: A Novel Opportunity for Smoking Cessation?

PMID- 26215211
TI  - Polypharmacy in Older Adults With Hypertension: A Comprehensive Review.
AB  - Older adults are more likely to take more than two medications for medical
      conditions, and polypharmacy is associated with increased risk of adverse events
      (fall injury, hyperkalemia and hypokalemia, heart failure, and blood pressure
      exacerbation), polypharmacy mismanagement, drug-drug interaction, and increased
      costs. Knowledge of drugs that interact with known antihypertensive agents is
      paramount to avoiding or reducing adverse events, hospitalizations, and health
      care dollars. Innovative approaches such as use of a fixed-dose combination pill,
      ingestible sensor system, electronic reminder system, medical audits, and the
      integration of a pharmacist in the care of patients should be implemented to
      avoid polypharmacy mismanagement. 

PMID- 26215213
TI  - A novel visible light mediated radical cyclization of enol lactones: a concise
      method for fluorinated polycyclic lactone scaffolds.
AB  - A novel visible light mediated radical cyclization of enol lactones with
      difluoroacyl arenes is presented. The reaction experienced a tandem radical
      cyclization and tolerated a wide range of substrates, resulting in fluorinated
      gamma-butyrolactones in good chemical yield and with excellent
      diastereoselectivity. 

PMID- 26215212
TI  - [NiFe]-hydrogenase is essential for cyanobacterium Synechocystis sp. PCC 6803
      aerobic growth in the dark.
AB  - The cyanobacterium Synechocystis sp. PCC 6803 has a bidirectional [NiFe]
      hydrogenase (Hox hydrogenase) which reversibly reduces protons to H2. This enzyme
      is composed of a hydrogenase domain and a diaphorase moiety, which is distinctly
      homologous to the NADH input module of mitochondrial respiratory Complex I. Hox
      hydrogenase physiological function is still unclear, since it is not required for
      Synechocystis fitness under standard growth conditions. We analyzed the phenotype
      under prolonged darkness of three Synechocystis knock-out strains, lacking either
      Hox hydrogenase (DeltaHoxE-H) or one of the proteins responsible for the assembly
      of its NiFe active site (DeltaHypA1 and DeltaHypB1). We found that Hox
      hydrogenase is required for Synechocystis growth under this condition, regardless
      of the functional status of its catalytic site, suggesting an additional role
      beside hydrogen metabolism. Moreover, quantitative proteomic analyses revealed
      that the expression levels of several subunits of the respiratory
      NADPH/plastoquinone oxidoreductase (NDH-1) are reduced when Synechocystis is
      grown in the dark. Our findings suggest that the Hox hydrogenase could contribute
      to electron transport regulation when both photosynthetic and respiratory
      pathways are down-regulated, and provide a possible explanation for the close
      evolutionary relationship between mitochondrial respiratory Complex I and
      cyanobacterial [NiFe]-hydrogenases. 

PMID- 26215214
TI  - In vitro fermentation of chewed mango and banana: particle size, starch and
      vascular fibre effects.
AB  - Fruits (and vegetables) contain cellular structures that are not degraded by
      human digestive enzymes. Therefore, the structure of the insoluble fraction of
      swallowed fruits is mostly retained until intestinal microbial fermentation. In
      vitro fermentation of mango and banana cell structures, which survived in vivo
      mastication and in vitro gastrointestinal digestion, were incubated with porcine
      faecal inoculum and showed intensive metabolic activity. This included
      degradation of cell walls, leading to the release of encapsulated cell contents
      for further microbial metabolism. Production of cumulative gas, short chain fatty
      acids and ammonia were greater for mango than for banana. Microscopic and
      spectroscopic analyses showed this was due to a major fermentation-resistant
      starch fraction present in banana, that was absent in mango. This study
      demonstrated distinctive differences in the fermentability of banana and mango,
      reflecting a preferential degradation of (parenchyma) fleshy cell walls over
      resistant starch in banana, and the thick cellulosic vascular fibres in mango. 

PMID- 26215215
TI  - Identification of accelerants, fuels and post-combustion residues using a
      colorimetric sensor array.
AB  - A linear (1 * 36) colorimetric sensor array has been integrated with a pre
      oxidation technique for detection and identification of a variety of fuels and
      post-combustion residues. The pre-oxidation method permits the conversion of fuel
      vapor into more detectable species and therefore greatly enhances the sensitivity
      of the sensor array. The pre-oxidation technique used a packed tube of chromic
      acid on an oxide support and was optimized in terms of the support and
      concentration. Excellent batch to batch reproducibility was observed for
      preparation and use of the disposable pre-oxidation tubes. Twenty automotive
      fuels including gasolines and diesel from five gasoline retailers were
      individually identifiable with no confusions or misclassifications in
      quintuplicate trials. Limits of detection were at sub-ppm concentrations for
      gasoline and diesel fuels. In addition, burning tests were performed on commonly
      used fire accelerants, and clear differentiation was achieved among both the
      fuels themselves and their volatile residues after burning. 

PMID- 26215216
TI  - A Technique to Facilitate Tooth Modification for Removable Partial Denture
      Prosthesis Guide Planes.
AB  - The technique in this article was developed to provide a means to create prepared
      guide planes of proper dimension to ensure a more stable and retentive removable
      partial denture prosthesis (RPDP) framework when providing this service for a
      patient. Using commonly found clinical materials, a paralleling device can be
      fabricated from the modified diagnostic cast of the patient's dental arch
      requiring an RPDP. Polymethyl methacrylate or composite added to an altered
      thermoplastic form can be positioned intraorally and used as a guide to
      predictably adjust tooth structure for guide planes. Since it can potentially
      minimize the number of impressions and diagnostic casts made during the
      procedure, this can help achieve the desired result more efficiently and quickly
      for the patient. 

PMID- 26215218
TI  - Ectopic Pancreas Presenting as a Solid Mediastinal Mass.
AB  - Ectopic pancreas is a well-known developmental anomaly found in approximately 2%
      of all autopsies, frequently in the gastrointestinal tract. Mediastinal
      pancreatic ectopia is very rare; only a few cases have been described in the
      English-language literature. According to previous reports, the pancreatic tissue
      is detected in the cyst wall or appears as small solid components of cystic
      masses within the anterior mediastinum. In this report, we present a case of
      ectopic pancreas appearing as a large solid mass in the anterior mediastinum of a
      17-year-old male patient. 

PMID- 26215217
TI  - A Wolf in Sheep's Clothing: A Sporadic Juvenile Polyp of the Colon Harboring an
      Intramucosal Adenocarcinoma.
AB  - We describe a solitary peduncolated polypoid lesion with a bilobated head in the
      transverse colon mucosa of a 51-year-old Caucasian man. Histologically, the
      lesion was consistent with juvenile polyp (JP), but showing a few dysplastic
      glands and a focus of intramucosal adenocarcinoma. This finding suggests that, at
      least in adults, even the sporadic JPs might carry an inherent potential for
      malignancy, which has so far only been pointed out for syndromic lesions.
      Additionally, we observed p53 overexpression in both the dysplastic lesions and
      in the invasive cells but not in the remaining epithelium. We can argue that p53
      immunohistochemistry may be helpful in differentiating hyperplastic regenerative
      atypia of the epithelium, frequently found in JPs, from true dysplasia, a much
      more rare change in the sporadic JPs. 

PMID- 26215219
TI  - Intraneural Extension of Synovial Sarcoma: Exceptional, or Simply
      Underrecognized?
AB  - Intraneural extension of soft tissue sarcomas is uncommon; it is most frequently
      seen in malignant peripheral nerve sheath tumor, but its occurrence is
      exceptional in synovial sarcoma. We describe a case arising extraneurally within
      the deep soft tissues of the forearm, which recurred and resulted in above-elbow
      amputation, revealing an unexpected finding of diffuse intraneural extension of
      tumor within a macroscopically normal major nerve. Despite macroscopic and
      microscopically clear soft tissue margins, the neoplasm had "traveled" a
      significant distance intraneurally to involve the neural resection margin. This
      feature does not appear to have been described before; it highlights the issue of
      whether intraneural spread of synovial sarcoma might have been previously
      underrecognized, and we discuss briefly some practical implications. 

PMID- 26215220
TI  - A Note of Caution: Variable Cytokeratin Staining in Sentinel Node Metastases.
AB  - Sentinel lymph node biopsy is the current standard procedure used to stage
      patients with breast cancer. The best histological method in evaluating sentinel
      nodes is highly debated among institutions and is thus not standardized. The
      optimal histological analysis is a balance between comprehensive evaluation of
      the sentinel nodes and cost effectiveness. One commonly used approach is serial
      sectioning and alternately staining with hemotoxylin and eosin and AE1/AE3
      cytokeratin immunohistochemistry analysis. We report 2 cases of metastatic
      carcinoma demonstrating negative staining for AE1/AE3. This observation
      highlights a rare but potential pitfall to this commonly used strategy in
      assessing sentinel lymph node biopsies in breast cancer. 

PMID- 26215221
TI  - Hepatobiliary IgG4 Cholangiopathy: Case Series and Literature Review.
AB  - IgG4 cholangiopathy is a recently described distinctive type of hepatobiliary
      manifestation of IgG4-related disease. This is often misdiagnosed as a malignancy
      of the hepatobiliary system on clinical presentation and imaging. Accurate
      diagnosis is crucial for appropriate management. Histopathology provides crucial
      information and is characterized by IgG4-positive lymphoplasmacytic infiltration
      with storiform fibrosis and obliterative phlebitis. We present the
      clinicopathological spectrum of a retrospective series of 6 cases of IgG4
      cholangiopathy that clinically masqueraded as hepatobiliary malignancies. 

PMID- 26215222
TI  - Lymphocytic Infiltration as a Prognostic Factor in Patients With Colon Cancer.
AB  - Host-defense mechanisms may have an important role in predicting the outcome of
      colorectal cancer patients. We designed our study to evaluate the possible
      prognostic significance of the presence of lymphocytic infiltration (LI) and
      subgroups of lymphocytes (CD3 and CD20) in the primary tumors. We randomly
      selected 195 patients operated for colorectal carcinoma from a larger cohort of
      1527 patients with colorectal cancer. Histological slides were blindly
      reevaluated for the presence of LI that was graded 0 to 3. Immunohistochemical
      phenotyping of the lymphocytes was performed only for tumors with LI score 3 and
      included antibodies CD3 and CD20. CD3 and CD20 immunostaining were graded in the
      same manner as LI. The mean duration of follow-up was 63.8 months. The
      distribution of patients with colorectal cancer according to LI scores was as
      follows: score 0, 20/195 (10.2%); score 1, 61/195 (31.3%); score 2, 78/195 (40%);
      and score 3, 36/195 (18.5%). There was no correlation between any
      clinicopathological pattern and LI. Score 3 staining for CD3 was more common than
      for CD20 (64.7% vs 8.8%, P < .0001). Prominent lymphocytic infiltration (score 3)
      was associated with better disease-free survival (P = .062). Recurrence was
      diagnosed among 2/22 (9.1%) patients with prominent CD3 staining versus 62/171
      (36.2%) of all other patient groups (P = .054) and they correspondingly had
      better disease-free survival (P = .018). It seems we can identify a group of
      patients with colorectal cancer who have an excellent prognosis according to a
      single immunological test unrelated to other known prognostic factors. 

PMID- 26215223
TI  - Desmoid Tumor of the Pancreas: Case Report and Review of a Rare Entity.
AB  - Desmoid tumors, also known as desmoid-type fibromatoses or aggressive
      fibromatoses, are clonal fibroblastic proliferations that arise in the deep soft
      tissues. They are characterized by infiltrative growth, a tendency toward local
      recurrence and the inability to metastasize. We present a case of a 63-year-old
      woman who complained of abdominal pain, and a contrast-enhanced computed
      tomography scan revealed a well-circumscribed tumor in the pancreatic tail,
      measuring 5.1 cm. A left-sided, spleen-preserving pancreatic resection was
      performed, and pathological analysis showed a mesenchymal tumor. The diagnosis of
      a pancreatic desmoid tumor was made based on the characteristic morphology and
      the immune phenotype of the tumor. The English-language literature on pancreatic
      desmoid tumors was reviewed. In total, 16 previous cases were identified. 

PMID- 26215224
TI  - Improving Balance in Older People: A Double-Blind Randomized  Clinical Trial of
      Three Modes of Balance Training.
AB  - The aim of this study was to examine and compare the effects of conventional,
      multisensory, and dual-task exercises on balance ability in a group of older
      community dwellers over a four-week period. Forty-four older people were randomly
      assigned to one of the three training groups. The score on the Fullerton Advanced
      Balance (FAB) scale, gait stability ratio, and walking speed were evaluated at
      baseline and after four weeks of training. All three groups showed significant (p
      < .001) improvement in the FAB scores following the three training programs (on
      average, 3 points for the conventional and multisensory groups and 3.8 points for
      the dual-task group). The improvements were comparable across the three
      intervention groups (p = .23). There were no statistically significant
      differences, neither within nor between groups, in the gait stability ratio and
      walking speed across the three training groups. In a four-week period, all the
      training modes were effective in improving balance of older adults, with no
      significant superiority of one mode of training over another.

PMID- 26215225
TI  - Trauma: A Potential Gateway to Primary Care.

PMID- 26215226
TI  - Conversion of a Remotely Performed Gastroplasty Procedure to a Roux-en-Y Gastric
      Bypass.

PMID- 26215227
TI  - Laparoscopic Right Hemicolectomy in a Morbidly Obese Patient Using a Medial
      Approach with an Intracorporeal Anastomosis.

PMID- 26215228
TI  - Comparison of Attending and Resident Surgeons' Opinions of Robotic Surgery
      Training in General Surgery Residency.

PMID- 26215229
TI  - Facial Fractures with Oronasal Hemorrhage in the Elderly: Impact on Outcome.

PMID- 26215230
TI  - An Unusual Case of Anorectal Avulsion after Blunt Traumatic Injury.

PMID- 26215231
TI  - Transabdominal Preperitoneal Inguinal Hernia Repair as a Salvage Operation after
      Failure of Prior Total Extraperitoneal Repair.

PMID- 26215232
TI  - Intracranial Hemangiopericytoma: A Rare but Aggressive Tumor.

PMID- 26215233
TI  - Constipation-Induced Acute Urinary Retention in the Intensive Care Unit.

PMID- 26215234
TI  - Moans, Bones, Groans, and a Thyroid Mass.

PMID- 26215235
TI  - A NSQIP Analysis of MELD and Perioperative Outcomes in General Surgery.
AB  - It is well known that liver disease has an adverse effect on postoperative
      outcomes. However, what is still unknown is how to appropriately risk stratify
      this patient population based on the degree of liver failure. Because data are
      limited, specifically in general surgery practice, we analyzed the model of end
      stage liver disease (MELD) in terms of predicting postoperative complications
      after one of three general surgery operations: inguinal hernia repair (IHR),
      umbilical hernia repair (UHR), and colon resection (CRXN). National Surgical
      Quality Improvement Program data on 17,812 total patients undergoing one of three
      general surgery operations from 2008 to 2012 were analyzed retrospectively. There
      were 7402 patients undergoing IHR; 5014 patients undergoing UHR; 5396 patients
      undergoing CRXN. MELD score was calculated using international normalized ratio,
      total bilirubin, and creatinine. The primary end point was any postoperative
      complication. The statistical method used was logistic regression. For IHR, UHR,
      and CRXN, the overall complication rates were 3.4, 6.4, and 45.9 per cent,
      respectively. The mean MELD scores were 8.6, 8.5, and 8.5, respectively. For
      every 1-point increase greater than the mean MELD score, there was a 7.8, 13.8,
      and 11.6 per cent increase in any postoperative complication. The overall 30-day
      mortality rate was 0.9 per cent. In conclusion, the MELD score continuum
      adequately predicts patients' increased risk of postoperative complications after
      IHR, UHR, and CRXN. Therefore, MELD could be used for preoperative risk
      stratification and guide clinical decision making for general surgery in the
      cirrhotic patient. 

PMID- 26215236
TI  - Safety of Outpatient Chest Tube Management of Air Leaks After Pulmonary
      Resection.
AB  - Prolonged air leaks are the most common postoperative complication following
      pulmonary resection, leading to increased hospital length of stay (LOS) and cost.
      This study assesses the safety of discharging patients home with a chest tube
      (CT) after pulmonary resection. A retrospective review was performed of a single
      surgeon's experience with pulmonary resections from January 2010 to January 2015.
      All patients discharged home with a CT were included. Discharge criteria included
      a persistent air leak controlled by water seal, resolution of medical conditions
      requiring hospitalization, and pain managed by oral analgesics. Patient
      demographics, type of resection, LOS, and 30-day morbidity and mortality data
      were analyzed. Comparisons were made with the Society of Thoracic Surgery
      database January 2011 to December 2013. Four hundred ninety-six patients
      underwent pulmonary resection. Sixty-five patients (13%) were discharged home
      postoperatively with a CT. Fifty-eight patients underwent a lobectomy, two
      patients a bilobectomy, and five patients had a wedge excision. Two patients were
      readmitted: One with a lower extremity deep venous thrombosis and the other with
      a nonlife threatening pulmonary embolus. Four patients developed superficial CT
      site infections that resolved after oral antibiotics. Patients discharged home
      with a CT following lobectomy had a shorter mean LOS compared to lobectomy
      patients (3.65 vs 6.2 days). Mean time to CT removal after discharge was 4.7 days
      (range 1-22 days) potentially saving 305 inpatient hospital days. Select patients
      can be discharged home with a CT with reduced postoperative LOS and without
      increase in major morbidity or mortality. 

PMID- 26215237
TI  - Surgical Site Occurrences of Simultaneous Panniculectomy and Incisional Hernia
      Repair.
AB  - Horizontal panniculectomy (PAN) offers the advantage of wide exposure for hernia
      repair with elimination of excess skin and adiposity, at the expense of massive
      subcutaneous flap creation and its attendant risks. We report our experience with
      ventral hernia repair (VHR) with PAN compared with patients with hernia repair
      alone. A prospective database was reviewed retrospectively for all patients
      undergoing open VHR + PAN. A matched cohort of patients without PAN was used for
      comparison, resulting in 43 study and 43 control patients. Incidence of surgical
      site occurrences (SSO), surgical site infection (SSI), and recurrence were
      analyzed. A total of 43 patients underwent PAN + VHR with mesh. Mean body mass
      index was 34.3 kg/m(2), with 35 per cent having undergone prior bariatric
      surgery. Repair techniques included retromuscular (74.4%), preperitoneal (11.6%),
      intraperitoneal (6.9%), onlay (4.6%), and suture (2.3%). Mesh used was
      polypropylene (76.7%), polyester (18.6%), bioabsorbable (2.3%), and
      polytetrafluoroethylene (ePTFE) (2.3%). Component separation was performed in
      44.2 per cent of patients. There was a significant difference in total SSO
      between PAN + VHR and VHR alone (46.5% vs 27.9%; P < 0.001), though the
      difference for individual SSOs was not significant. There was no difference in
      SSI between groups (16.3% vs 20.9%; P = 0.776). Mean follow-up was 11.4 months,
      with recurrence rate of 11.6 per cent in the PAN group and 9.3 per cent in the
      control group (P = 0.725). Panniculectomy at the time of VHR does not increase
      the incidence of SSI, though higher rates of skin necrosis and cellulitis were
      seen. There is no difference in recurrence. This approach is a valid option for
      patients with excessive abdominal panniculus requiring VHR. 

PMID- 26215238
TI  - Permissive Hypotension: Potentially Harmful in the Elderly? A National Trauma
      Data Bank Analysis.
AB  - Permissive hypotension is a component of damage control resuscitation that aims
      to provide a directed, controlled resuscitation, while countering the "lethal
      triad." This principle has not been specifically studied in elderly (ELD) trauma
      patients (>=55 years). Given the ELD population's lack of physiologic reserve and
      risk of inadequate perfusion with "normal" blood pressures, we hypothesized that
      utilized a permissive hypotension strategy in ELD trauma patients would result in
      worse outcomes compared with younger patients (18-54 years). A retrospective
      review of National Trauma Data Bank reports from 2009 and 2010, identifying
      critically ill patients undergoing a "damage control laparotomy," was performed
      to determine the effect of age and systolic blood pressure on outcome. Logistic
      regression analysis, including evaluation of an interaction between age and
      admission blood pressure, was performed on mortality using admission
      demographics, physiology, injury severity, mechanism of injury, and in-hospital
      complications. Although there was a higher likelihood of death with greater age,
      lower admission systolic blood pressure, lower Glasgow Coma Score, increased
      injury severity score, and acute renal failure, a synergistic effect of age and
      blood pressure on mortality was not identified. Permissive hypotension appears to
      be a possible management strategy in ELD trauma patients. 

PMID- 26215239
TI  - National Outcomes for Open Ventral Hernia Repair Techniques in Complex Abdominal
      Wall Reconstruction.
AB  - Modern adjuncts to complex, open ventral hernia repair often include component
      separation (CS) and/or panniculectomy (PAN). This study examines nationwide data
      to determine how these techniques impact postoperative complications. The
      National Surgical Quality Improvement Program database was queried from 2005 to
      2013 for inpatient, elective open ventral hernia repairs (OVHR). Cases were
      grouped by the need for and type of concomitant advancement flaps: OVHR alone
      (OVHRA), OVHR with CS, OVHR with panniculectomy (PAN), or both CS and PAN (BOTH).
      Multivariate regression to control for confounding factors was conducted. There
      were 58,845 OVHR: 51,494 OVHRA, 5,357 CS, 1,617 PAN, and 377 BOTH. Wound
      complications (OVHRA 8.2%, CS 12.8%, PAN 14.4%, BOTH 17.5%), general
      complications (15.2%, 24.9%, 25.2%, 31.6%), and major complications (6.9%, 11.4%,
      7.2%, 13.5%) were different between groups (P < 0.0001). There was no difference
      in mortality. Multivariate regression showed CS had higher odds of wound [odds
      ratio (OR) 1.7, 95% confidence interval (CI) 1.5-2.0], general (OR 1.5, 95% CI:
      1.3-1.8), and major complications (OR 2.1, 95%, CI: 1.8-2.4), and longer length
      of stay by 2.3 days. PAN had higher odds of wound (OR 1.5, 95%, CI: 1.3-1.8) and
      general complications (OR 1.7, 95%CI: 1.5-2.0). Both CS and PAN had higher odds
      of wound (OR 2.2, 95%, CI: 1.5-3.2), general (OR 2.5, 95%, CI: 1.8-3.4), and
      major complications (OR 2.2, 95%CI: 1.4-3.4), and two days longer length of stay.
      In conclusion, patients undergoing OVHR that require CS or PAN have a higher
      independent risk of complications, which increases when the procedures are
      combined. 

PMID- 26215240
TI  - Present Status of Autonomy in Surgical Residency--a Program Director's
      Perspective.
AB  - As surgery residents graduate and begin their careers as junior attending
      surgeons, the question of whether a surgeon can complete a case alone still
      lingers. Allowing autonomy during residency answers this question. The purpose of
      this study was to gather input from general surgery residency program directors
      on how they achieve autonomy for residents in their programs. An online survey of
      18 questions was sent to all general surgery residency program directors in the
      United States between April and June of 2013 via e-mail. Questions were asked
      regarding classification of autonomy, percentage of case completed by the
      resident independently, and in what area a resident worked with minimal
      supervision. Of the 202 delivered, 85 program directors were responded (42%).
      Seventy-eight per cent of programs classified a resident as surgeon junior
      whether the resident completed more than 50 per cent of the case. Most classified
      autonomy as either the resident completing >75 per cent of a case (41%) or
      completing the critical steps of a surgery (41%). Eighty-eight per cent stated
      that chief residents completed the majority of cases under supervision, whereas
      only 12 per cent stated the chief had autonomy in the operating room and also
      acted as teaching assistant. While, 60 per cent stated their chief residents did
      not work in any area of the hospital independently. Despite differences in how
      autonomy is defined among programs, most program directors feel that their chief
      residents do not achieve complete autonomy. Programs should allow their residents
      to work in a progressive responsibility as they progress into their fourth and
      fifth years of residency to achieve autonomy. 

PMID- 26215241
TI  - A Single Institution's First 100 Patients Undergoing Laparoscopic Anti-Reflux
      Fundoplications: Where Are They 20 Years Later?
AB  - Although anti-reflux surgery has been used liberally over the past decades for
      the treatment of gastroesophageal reflux disease (GERD), few studies report
      follow-up after 10 years. This study was undertaken to report follow-up on 100
      consecutive GERD patients up to 22 years after utilizing a laparoscopic
      fundoplication. Hundred consecutive patients undergoing laparoscopic
      fundoplication for GERD were prospectively followed beginning in 1992. The
      frequency and severity of symptoms before and after laparoscopic fundoplication
      were scored on a Likert scale (1 = never/none to 10 = always/very bothersome).
      Median data are reported. Of the 100 patients who underwent laparoscopic
      fundoplication for their GERD, nine were reoperations. Twenty-six patients are
      deceased on average 11 years after their fundoplications. Seventy-four patients
      are alive, with 27 patients, actively followed for 19 years after their
      fundoplications. At most recent follow-up, patients experienced long-term
      amelioration of symptom frequency and severity after fundoplication (e.g.,
      heartburn frequency = 8-2, severity = 8-1; P < 0.01 for each). Eighty-four per
      cent of patients rated their symptom frequency as less than once per month.
      Eighty-eight per cent of patients were satisfied with their postoperative
      results, and 95 per cent of patients confirmed they would have the operation
      again knowing what they know now. Long-term follow-up documents high patient
      satisfaction and durable symptomatic relief up to two decades after laparoscopic
      fundoplication for GERD. Patients should seek this operation not only for
      symptomatic relief, but to mitigate the deleterious effects of long-term acid
      exposure and anti-acid therapy. 

PMID- 26215242
TI  - Torso Computed Tomography Can Be Bypassed after Thorough Trauma Bay Examination
      of Patients Who Fall from Standing.
AB  - Reliance on CT imaging in the evaluation of low-impact blunt trauma is a major
      source of radiation exposure, cost, and resource utilization. This study sought
      to determine if torso (chest and abdomen) CT could be avoided in patients with
      ground level falls. This was a retrospective chart review of patients admitted to
      the trauma service between January 2013 and April 2014. The mechanism of injury
      was ground level fall or fall from sitting. Patient demographics, physical
      examination (PE) findings, imaging results, length of stay, and complications
      were reviewed. History and physical data were based on chief resident or
      attending documentation. A significant thoracic injury was defined as a
      hemothorax, a pneumothorax, greater than three rib fractures, or aortic injury. A
      significant abdominal injury was defined as a solid organ injury, an intra
      abdominal hematoma, a hollow viscus injury, aortic injury, or a urologic injury.
      The trauma service evaluated 156 patients. Nine patients were excluded for
      intubation or Glasgow Coma Scale (GCS) < 13. Of the 147 remaining, mean age was
      69 years, mean GCS was 14.8. A chest CT was obtained in 111 (76%). Eight (7%) had
      a significant thoracic injury. All patients with significant thoracic injury had
      positive examination findings. No patient with a normal PE was found to have a
      significant thoracic injury (negative predictive value of 100%). An abdominal CT
      was obtained in 86 (59%). Five (6%) were found to have a significant abdominal
      injury. All patients who had a significant radiographic injury had an abnormal PE
      (negative predictive value of 100%). In conclusion, thorough history and physical
      in the trauma bay allow the clinician to obtain selective torso CT imaging.
      Routine torso CT warrants re-evaluation in low-impact injury mechanisms as there
      appears to be little benefit compared with the resource utilization and expense. 

PMID- 26215243
TI  - Dramatic Increase in the Incidence and Mortality from Merkel Cell Carcinoma in
      the United States.
AB  - Merkel cell carcinoma is a cutaneous neuroendocrine neoplasm that has been poorly
      studied in contemporary cohorts. Patients with Merkel cell carcinoma from 1986 to
      2011 were identified in the Surveillance Epidemiology and End Results registry. A
      total of 5211 patients met the inclusion criteria. The mean age was 74.9 years;
      majority were male (61.4%) and white (94.9%). Patients were divided into two
      cohorts: Group 1 (1986 and 1999) and Group 2 (1999-2010). Group 2 was more likely
      to have Stage III disease (14.6 vs 23.3%, P < 0.001) and less likely to have
      Stage I/II disease (71.8 vs 65.1%, P < 0.0001). The increase in Stage III was
      likely secondary to increased use of sentinel lymph node biopsy. Disease-specific
      five-year survival for Stages I/II was 78.1 per cent and Stage III was 54 per
      cent. Disease-specific five-year survival was unchanged between Groups 1 and 2,
      69.9 versus 66.6 per cent, respectively (P = 0.44). Both incidence and mortality
      significantly increased over the study period with P value for both trends
      <0.0001. In 1986, incidence and mortality rates per 100,000 were 0.22 and 0.03,
      respectively, and increased to 0.79 and 0.43 in 2011, respectively. There has
      been a greater than 333 per cent increase in mortality from Merkel cell
      carcinoma. 

PMID- 26215244
TI  - Cost-effectiveness of Bariatric Surgery: Increasing the Economic Viability of the
      Most Effective Treatment for Type II Diabetes Mellitus.
AB  - There has been considerable debate on the cost-effectiveness of bariatric surgery
      within larger population groups. Despite the recognition that morbid obesity and
      its comorbidities are best treated surgically, insurance coverage is not
      universally available. One of the more costly comorbidities of obesity is Type II
      diabetes mellitus (T2DM). We propose a model that demonstrates the cost
      effectiveness of increasing the number of bariatric surgical operations performed
      on patients with T2DM in the United States. We applied published population cost
      estimates (2012) for medical care of T2DM to a retrospective cohort of morbidly
      obese patients in South Carolina. We compared differences in 10-year medical
      costs between those having bariatric surgery and controls. Resolution of T2DM in
      the bariatric cohort was assumed to be 40 per cent. Considering only the direct
      medical costs of T2DM, the 10-year aggregate cost savings compared with a control
      group is $2.7 million/1000 patients; the total (direct and indirect) cost savings
      is $5.4 million/1000 patients. When considering resolution of T2DM alone,
      increasing the number of bariatric operations for a given population leads to a
      substantial cost savings over a 10-year period. This study adds to the growing
      body of evidence suggesting that bariatric surgery is a cost-effective means of
      caring for the obese patient. 

PMID- 26215245
TI  - Preservation of Fat-free Mass after Bariatric Surgery: A Comparison of
      Malabsorptive and Restrictive Procedures.
AB  - The Roux-en-Y gastric bypass (RYGB) has been shown to cause significant weight
      loss. However, fat-free mass (FFM) is often lost with this rapid weight change.
      It is suggested that the loss of FFM is minimized with restrictive-only
      procedures, such as the vertical sleeve gastrectomy (VSG), when compared with
      malabsorptive surgery. The purpose of the study was to determine the difference
      in the postoperative loss of FFM between RYBG and VSG patients. We reviewed all
      patients who underwent RYGB or VSG between May 2012 and January 2013. Patients
      were evaluated one month before their procedure and 12 months after for
      comparison of results. Preoperative and postoperative body analysis data were
      procured using a body composition analysis device. Within the study period, 33
      patients underwent a RYGB procedure and 20 patients a VSG. After 12 months, RYGB
      patients had an average increase of 38.15 per cent in their proportion of FFM,
      whereas VSG patients had an average FFM increase of 22.09 per cent, a statically
      significant difference (P = 0.004). The RYGB helps preserve overall FFM as
      compared with the VSG. These findings are unexpected because malabsorptive
      procedures require increased protein intake, resulting in a stronger likelihood
      of inadequate protein intake, which may lead to protein malnutrition. 

PMID- 26215246
TI  - Understanding Gram-negative Central Line-Associated Blood Stream Infection in a
      Surgical Trauma ICU.
AB  - The purpose of this study was to review central line-associated blood stream
      infection (CLABSI) data from a surgical trauma intensive care unit to better
      understand patient risk factors, pathogens, and treatment interventions. We
      performed a retrospective review of all surgical ICU patients who met the Centers
      for Disease Control definition for Gram-negative CLABSI from 2006 through 2013.
      Demographics, pathogens, interventions, and outcomes were evaluated. A total of
      40 patients were included with an average age of 49.9 +/- 19 years and 72.5 per
      cent male. The average length of central venous line (CVL) was 11 +/- 5.9 days
      with average time from line placement to positive culture 9.4 +/- 6.8 days. Most
      common organisms were Enterobacter species (37.5%) with 17.8 per cent of all
      cultured organisms considered multidrug resistant. Piperacillin-tazobactam
      (67.5%) was the most commonly used antibiotic. Overall mortality rate was 22.5
      per cent. A total of 11 patients who developed a recurrence did so at 10.7 +/- 8
      days and were similar to those without recurrence. Predominant pathogens
      associated with surgical trauma intensive care unit CLABSI in this study are
      different from those Gram-negative bacteria associated with published studies in
      the general hospital population. Further investigation into risk factors for
      infection and relapse is important to minimize such consequences. Understanding
      appropriate line placement and use as well as clarifying optimal duration of
      therapy is integral in improving outcomes. 

PMID- 26215247
TI  - Risk Factors for Postoperative Unplanned Intubation: Analysis of a National
      Database.
AB  - Postoperative unplanned intubation (PUI) is a significant complication and is
      associated with severe adverse events and mortality. By participating in the
      National Surgical Quality Improvement Program (NSQIP), we learned that PUI
      occurred more frequently than expected at our institution. The aim of this study
      was to identify risk factors that are predictors of PUI at our institution. We
      reviewed the NSQIP data from our institution and the NSQIP national database for
      surgery patients from 2010 through 2013. The rate of PUI at our institution was
      1.54 per cent compared with the national rate of 1.03 per cent. Perioperative
      risk factors were analyzed by multivariate logistic regression. Analysis of the
      national NSQIP database identified 14 independent risk factors for PUI. Analysis
      of the NSQIP data at our institution demonstrated that emergent cases,
      preoperative ventilator status, smoking, chronic obstructive pulmonary disease,
      and older age were independent risk factors. In conclusion, patients at our
      institution with these five risk factors were at higher risk of requiring PUI.
      These risk factors could be used to help identify patients at high risk and
      possibly help prevent postoperative respiratory failure and unplanned intubation.

PMID- 26215248
TI  - Effect of Pain Medication Choice on Emergency Room Visits for Pain after
      Ambulatory Laparoscopic Cholecystectomy.
AB  - Inadequate pain control after ambulatory surgery can lead to unexpected return
      visits to the hospital. The purpose of this study was to compare patients based
      on which medications they were prescribed and to see whether this affected the
      rate of return to the hospital. A retrospective chart review of patients who
      underwent ambulatory laparoscopic cholecystectomy between January 2009 and
      December 2013 was performed. Patients were divided into two groups based on the
      pain medication prescribed after surgery: Opioids and nonopioids. Patients
      returning to the Emergency room (ER) within seven days were evaluated. If no
      complication or other diagnosis was identified, the patient was considered to
      have returned for inadequate pain control. The two groups were statistically
      compared with each other using Fisher's exact chi-squared test. A total of 749
      patients underwent laparoscopic cholecystectomy during the study period: 180
      (25.2%) were prescribed opioids, whereas, 560 (74.8%) were prescribed nonopioids.
      In the nonopioid group, 14 (1.9%) returned to the ER for pain, whereas no patient
      in the opioid group returned for pain. This difference was statistically
      significant (P = 0.027). In conclusion, patients who were given opioid pain
      medications after ambulatory laparoscopic cholecystectomy were less likely to
      return to the ER for pain. This implied that opioids were better at pain control
      and helped avoid the costs of unnecessary ER visits. Future research should be
      aimed at more direct measures of pain control, as well as the role of opioids
      after inpatient surgery. 

PMID- 26215249
TI  - Emergency General Surgery: Defining Burden of Disease in the State of Maryland.
AB  - Acute care surgery services continue expanding to provide emergency general
      surgery (EGS) care. The aim of this study is to define the characteristics of the
      EGS population in Maryland. Retrospective review of the Health Services Cost
      Review Commission database from 2009 to 2013 was performed. American Association
      for the Surgery of Trauma-defined EGS ICD-9 codes were used to define the EGS
      population. Data collected included patient demographics, admission origin
      [emergency department (ED) versus non-ED], length of stay (LOS), mortality, and
      disposition. There were 3,157,646 encounters. In all, 817,942 (26%) were EGS
      encounters, with 76 per cent admitted via an ED. The median age of ED patients
      that died was 74 years versus 61 years for those that lived (P < 0.001). Twenty
      one per cent of ED admitted patients had a LOS > 7 days. Of 78,065 non-ED
      admitted patients, the median age of those that died was 68 years versus 59 years
      for those that lived (P < 0.001). Twenty eight per cent of non-ED admits had LOS
      > 7 days. In both ED and non-ED patients, there was a bimodal distribution of
      death, with most patients dying at LOS <= 2 or LOS > 7 days. In this study, EGS
      diagnoses are present in 26 per cent of inpatient encounters in Maryland. The EGS
      population is elderly with prolonged LOS and a bimodal distribution of death. 

PMID- 26215250
TI  - Access to primary care is associated with better autoimmune hepatitis outcomes in
      an urban county hospital.
AB  - BACKGROUND: Autoimmune hepatitis causes chronic hepatitis and often leads to
      cirrhosis and death without treatment. We wanted to see if having access to
      primary care or insurance prior to diagnosis is associated with better outcomes
      for patients in an urban, public hospital with mostly socioeconomically
      disadvantaged Hispanic patients. METHODS: We did a retrospective study at our
      institution. Kaplan Meier survival analysis was done looking at transplant-free
      overall survival for patients diagnosed at our institution. The log-rank test was
      done to compare survival between patients with and without prior access to
      primary care, and between patients with and without insurance at diagnosis.
      RESULTS: Overall 5- and 10-year transplant-free overall survival was 91% (95% CI,
      83-100%) and 75% (95% CI, 50-99%), respectively. Patients with primary care prior
      to diagnosis had significantly better transplant-free overall survival than those
      without (log rank test p = 0.019). Patients with primary care also had better
      clinical markers at diagnosis. Having insurance at diagnosis was not associated
      with better outcomes. CONCLUSIONS: Outcomes of autoimmune hepatitis are poor in
      our setting but access to primary care prior to diagnosis was associated with
      better outcomes. This is likely due to the important role that primary care plays
      in detecting disease and initiating treatment earlier. With the expansion of
      access to healthcare that the Affordable Care Act provides, future patients are
      likely to do better with even rare diseases like autoimmune hepatitis.

PMID- 26215251
TI  - Quantum Monte Carlo study of the phase diagram of solid molecular hydrogen at
      extreme pressures.
AB  - Establishing the phase diagram of hydrogen is a major challenge for experimental
      and theoretical physics. Experiment alone cannot establish the atomic structure
      of solid hydrogen at high pressure, because hydrogen scatters X-rays only weakly.
      Instead, our understanding of the atomic structure is largely based on density
      functional theory (DFT). By comparing Raman spectra for low-energy structures
      found in DFT searches with experimental spectra, candidate atomic structures have
      been identified for each experimentally observed phase. Unfortunately, DFT
      predicts a metallic structure to be energetically favoured at a broad range of
      pressures up to 400 GPa, where it is known experimentally that hydrogen is non
      metallic. Here we show that more advanced theoretical methods (diffusion quantum
      Monte Carlo calculations) find the metallic structure to be uncompetitive, and
      predict a phase diagram in reasonable agreement with experiment. This greatly
      strengthens the claim that the candidate atomic structures accurately model the
      experimentally observed phases. 

PMID- 26215252
TI  - Feline hippocampal and piriform lobe necrosis as a consequence of severe cluster
      seizures in two cats in Finland.
AB  - Feline hippocampal and piriform lobe necrosis (FHN) has been reported from
      several countries worldwide and is considered an important aetiology for feline
      epileptic seizures. The aetiology of FHN remains unclear, however it is suspected
      that FHN might occur secondary to intense epileptic activity as described in
      humans and dogs although this has not yet been documented in cats. The purpose of
      our report is to describe the first cases of FHN in Finland diagnosed by magnetic
      resonance imaging (MRI) and histopathology. The two cases we describe had a well
      documented history of pre-existing seizures with normal brain MRI at the onset of
      cluster seizures but MRI done when the cats exhibited clinical deterioration
      secondary to severe seizure activity, revealed lesions in the hippocampus and
      piriform lobes typical of FHN. Our report confirms that feline hippocampus and
      piriform lobe necrosis does occur in the Finnish cat population and should
      therefore be considered as a differential diagnosis in cats with seizures. In
      addition, the presentation, clinical findings, results of MRI and/or
      histopathology shows that cats may develop FHN secondary to severe seizure
      activity. 

PMID- 26215253
TI  - Cyclometalated Iridium(III) Complexes as Two-Photon Phosphorescent Probes for
      Specific Mitochondrial Dynamics Tracking in Living Cells.
AB  - Five cyclometalated iridium(III) complexes with 2-phenylimidazo[4,5
      f][1,10]phenanthroline derivatives (IrL1-IrL5) were synthesized and developed to
      image and track mitochondria in living cells under two-photon (750 nm)
      excitation, with two-photon absorption cross-sections of 48.8-65.5 GM at 750 nm.
      Confocal microscopy and inductive coupled plasma-mass spectrometry (ICP-MS)
      demonstrated that these complexes selectively accumulate in mitochondria within 5
      min, without needing additional reagents for membrane permeabilization, or
      replacement of the culture medium. In addition, photobleaching experiments and
      luminescence measurements confirmed the photostability of these complexes under
      continuous laser irradiation and physiological pH resistance. Moreover, results
      using 3D multicellular spheroids demonstrate the proficiency of these two-photon
      luminescent complexes in deep penetration imaging. Two-photon excitation using
      such novel complexes of iridium(III) for exclusive visualization of mitochondria
      in living cells may substantially enhance practical applications of bioimaging
      and tracking.

PMID- 26215254
TI  - Barriers and Facilitators of Mental Health Treatment-Seeking in U.S. Active Duty
      Soldiers With Sexual Assault Histories.
AB  - Despite significant mental health needs among sexual assault (SA) victims in the
      military, little is known about treatment-seeking patterns or factors associated
      with service use. This study examined service use behavior, barriers, and
      facilitators of mental health treatment-seeking in an active duty sample of 927
      U.S. Army soldiers with mental health problems. SA victims (n = 113) did not
      differ from non-victims on barriers or facilitators after adjusting for
      demographic and mental health variables, with stigma rated as the largest
      barrier. Most SA victims (87.6%) had sought informal support and 59.3% had sought
      formal treatment. One third of treatment-seekers had dropped out of treatment.
      Multivariate logistic regression analyses identified several correlates of
      treatment-seeking among SA victims: Black race (OR = 7.57), SA during the
      military (OR = 4.34), positive treatment beliefs (OR = 2.22), social support for
      treatment (OR = 2.14), self-reliance (OR = 0.47), and stigma towards treatment
      seekers (OR = 0.43). Mental health symptoms were not associated with treatment
      seeking. Findings suggested that treatment-facilitating interventions should
      focus on improving recognition of mental health symptoms, altering perceptions
      related to self-reliance, and reducing stigma. Interventions should also enlist
      support for treatment-seeking from unit members, leaders, and significant others.

PMID- 26215255
TI  - Head-to-Tail Zig-Zag Packing of Dipolar Merocyanine Dyes Affords High-Performance
      Organic Thin-Film Transistors.
AB  - Attachment of bulky substituents at both thiophene donor (D) and thiazole
      acceptor (A) heterocycles of a dipolar (MU(g)=10.4 D) D-pi-A merocyanine dye
      affords a more than 1 A expansion of the common antiparallel supramolecular dimer
      motif in the solid state, enabling very close pi-contacts (3.36 A) to two other
      neighbor molecules on each of the two remaining pi-faces. This unusual packing
      motif leads to three-dimensional percolation pathways for hole transport and
      affords thin-film transistors with mobility up to 0.64 cm(2)  V(-1)  s(-1).

PMID- 26215256
TI  - Cluster-pi electronic interaction in a superatomic Au13 cluster bearing sigma
      bonded acetylide ligands.
AB  - An organometallic Au13 cluster having two sigma-bonded acetylide ligands was
      synthesized and its structure was determined by X-ray crystallography. Absorption
      spectral studies indicated the presence of electronic coupling between the
      superatomic Au13 core and the acetylide pi-orbitals, which was supported by
      theoretical considerations. 

PMID- 26215257
TI  - Muscle ring finger-3 protects against diabetic cardiomyopathy induced by a high
      fat diet.
AB  - BACKGROUND: The pathogenesis of diabetic cardiomyopathy (DCM) involves the
      enhanced activation of peroxisome proliferator activating receptor (PPAR)
      transcription factors, including the most prominent isoform in the heart,
      PPARalpha. In cancer cells and adipocytes, post-translational modification of
      PPARs have been identified, including ligand-dependent degradation of PPARs by
      specific ubiquitin ligases. However, the regulation of PPARs in cardiomyocytes
      and heart have not previously been identified. We recently identified that muscle
      ring finger-1 (MuRF1) and MuRF2 differentially inhibit PPAR activities by mono
      ubiquitination, leading to the hypothesis that MuRF3 may regulate PPAR activity
      in vivo to regulate DCM. METHODS: MuRF3-/- mice were challenged with 26 weeks 60%
      high fat diet to induce insulin resistance and DCM. Conscious echocardiography,
      blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of
      intracellular signaling, heart and skeletal muscle morphometrics, and PPARalpha,
      PPARbeta, and PPARgamma1 activities were assayed. RESULTS: MuRF3-/- mice
      exhibited a premature systolic heart failure by 6 weeks high fat diet (vs. 12
      weeks in MuRF3+/+). MuRF3-/- mice weighed significantly less than sibling-matched
      wildtype mice after 26 weeks HFD. These differences may be largely due to
      resistance to fat accumulation, as MRI analysis revealed MuRF3-/- mice had
      significantly less fat mass, but not lean body mass. In vitro ubiquitination
      assays identified MuRF3 mono-ubiquitinated PPARalpha and PPARgamma1, but not
      PPARbeta. CONCLUSIONS: These findings suggest that MuRF3 helps stabilize cardiac
      PPARalpha and PPARgamma1 in vivo to support resistance to the development of DCM.
      MuRF3 also plays an unexpected role in regulating fat storage despite being found
      only in striated muscle.

PMID- 26215258
TI  - Transcriptome analysis of bacteriophage communities in periodontal health and
      disease.
AB  - BACKGROUND: The role of viruses as members of the human microbiome has gained
      broader attention with the discovery that human body surfaces are inhabited by
      sizeable viral communities. The majority of the viruses identified in these
      communities have been bacteriophages that predate upon cellular microbiota rather
      than the human host. Phages have the capacity to lyse their hosts or provide them
      with selective advantages through lysogenic conversion, which could help
      determine the structure of co-existing bacterial communities. Because conditions
      such as periodontitis are associated with altered bacterial biota, phage mediated
      perturbations of bacterial communities have been hypothesized to play a role in
      promoting periodontal disease. Oral phage communities also differ significantly
      between periodontal health and disease, but the gene expression of oral phage
      communities has not been previously examined. RESULTS: Here, we provide the first
      report of gene expression profiles from the oral bacteriophage community using
      RNA sequencing, and find that oral phages are more highly expressed in subjects
      with relative periodontal health. While lysins were highly expressed, the high
      proportion of integrases expressed suggests that prophages may account for a
      considerable proportion of oral phage gene expression. Many of the transcriptome
      reads matched phages found in the oral cavities of the subjects studied,
      indicating that phages may account for a substantial proportion of oral gene
      expression. Reads homologous to siphoviruses that infect Firmicutes were amongst
      the most prevalent transcriptome reads identified in both periodontal health and
      disease. Some genes from the phage lytic module were significantly more highly
      expressed in subjects with periodontal disease, suggesting that periodontitis may
      favor the expression of some lytic phages. CONCLUSIONS: As we explore the
      contributions of viruses to the human microbiome, the data presented here suggest
      varying expression of bacteriophage communities in oral health and disease.

PMID- 26215260
TI  - Genetics: Response to antidiabetic drugs affected by SNPs that alter genomic
      binding of PPARgamma.

PMID- 26215261
TI  - Diabetes: Dysglycaemia as a cause of cardiovascular outcomes.

PMID- 26215266
TI  - Characterizing LipR from Pseudomonas sp. R0-14 and Applying in Enrichment of
      Polyunsaturated Fatty Acids from Algal Oil.
AB  - In this study, Pseudomonas R0-14, which was isolated from Arctic soil samples,
      showed a clear halo when grown on M9 medium agarose plates containing olive oil
      rhodamine B as substrate, suggesting that it expressed putative lipase(s). A
      putative lipase gene, lipR, was cloned from R0-14 by genome walking and Touchdown
      PCR. lipR encodes a 562-amino-acid polypeptide showing a typical alpha/beta
      hydrolase structure with a catalytic triad consisting of Ser153-Asp202-His260 and
      one alpha-helical lid (residues 103-113). A phylogenetic analysis revealed that
      LipR belongs to the lipase subfamily I.3. LipR was successfully expressed in
      Escherichia coli, purified, and biochemically characterized. Recombinant LipR
      exhibited its maximum activity towards p-nitrophenyl butyrate at pH 8.5 and 60
      degrees C with a Km of 0.37 mM and a kcat of 6.42 s(-1). It retained over 90% of
      its original activity after incubation at 50 degrees C for 12 h. In addition,
      LipR was activated by Ca(2+), Mg(2+), Ba(2+), and Sr(2+), while strongly
      inhibited by Cu(2+), Zn(2+), Mn(2+), and ethylenediaminetetraacetic acid.
      Moreover, it showed a certain tolerance to organic solvents, including
      acetonitrile, isopropanol, acetone, methanol, and tert-butanol. When algal oil
      was hydrolyzed by LipR for 24 h, there was an enrichment of n-3 long-chain
      polyunsaturated fatty acids, including eicosapentaenoic acid (1.22%, 1.65-fold),
      docosapentaenoic acid (21.24%, 2.04-fold), and docosahexaenoic acid (36.98%, 1.33
      fold), and even a certain amount of diacylglycerols was also produced. As a
      result, LipR has great prospect in industrial applications, especially in food
      and/or cosmetics applications. 

PMID- 26215259
TI  - Physiological and pathophysiological roles of NAMPT and NAD metabolism.
AB  - Nicotinamide phosphoribosyltransferase (NAMPT) is a regulator of the
      intracellular nicotinamide adenine dinucleotide (NAD) pool. NAD is an essential
      coenzyme involved in cellular redox reactions and is a substrate for NAD
      dependent enzymes. In various metabolic disorders and during ageing, levels of
      NAD are decreased. Through its NAD-biosynthetic activity, NAMPT influences the
      activity of NAD-dependent enzymes, thereby regulating cellular metabolism. In
      addition to its enzymatic function, extracellular NAMPT (eNAMPT) has cytokine
      like activity. Abnormal levels of eNAMPT are associated with various metabolic
      disorders. NAMPT is able to modulate processes involved in the pathogenesis of
      obesity and related disorders such as nonalcoholic fatty liver disease (NAFLD)
      and type 2 diabetes mellitus (T2DM) by influencing the oxidative stress response,
      apoptosis, lipid and glucose metabolism, inflammation and insulin resistance.
      NAMPT also has a crucial role in cancer cell metabolism, is often overexpressed
      in tumour tissues and is an experimental target for antitumour therapies. In this
      Review, we discuss current understanding of the functions of NAMPT and highlight
      progress made in identifying the physiological role of NAMPT and its relevance in
      various human diseases and conditions, such as obesity, NAFLD, T2DM, cancer and
      ageing. 

PMID- 26215267
TI  - Molecular Cloning and Co-Expression of Phytoene Synthase Gene from Kocuria
      gwangalliensis in Escherichia coli.
AB  - A phytoene synthase gene, crtB, was isolated from Kocuria gwangalliensis. The
      crtB with 1,092 bp full-length has a coding sequence of 948 bp and encodes a 316
      amino-acids protein. The deduced amino acid sequence showed a 70.9% identity with
      a putative phytoene synthase from K. rhizophila. An expression plasmid, pCcrtB,
      containing the crtB gene was constructed, and E. coli cells containing this
      plasmid produced the recombinant protein of approximately 34 kDa , corresponding
      to the molecular mass of phytoene synthase. Biosynthesis of lycopene was
      confirmed when the plasmid pCcrtB was co-transformed into E. coli containing
      pRScrtEI carrying the crtE and crtI genes encoding lycopene biosynthetic pathway
      enzymes. The results obtained from this study will provide a base of knowledge
      about the phytoene synthase of K. gwangalliensis and can be applied to the
      production of carotenoids in a non-carotenoidproducing host.

PMID- 26215268
TI  - Purification and Characterization of a Novel Extracellular Thermostable Alkaline
      Protease from Streptomyces sp. M30.
AB  - A novel alkaline protease from Streptomyces sp. M30, SapHM, was purified by
      ammonium sulfate precipitation, hydrophobic interaction chromatography, and DEAE
      Sepharose chromatography, with a yield of 15.5% and a specific activity of 29,070
      U/mg. Tryptic fragments of the purified SapHM were obtained by electrospray
      ionization quadrupole time-of- flight mass spectrometry. Nucleotide sequence
      analysis revealed that the gene sapHM contained 1,179 bp, corresponding to 392
      amino acids with conserved Asp156, His187, and Ser339 residues of alkaline
      protease. The first 24 amino acid residues were predicted to be a signal peptide,
      and the molecular mass of the mature peptide was 37.1 kDa based on amino acid
      sequences and mass spectrometry. Pure SapHM was optimally active at 80 degrees C
      in 50 mM glycine-NaOH buffer (pH 9.0), and was broadly stable at 0-50  degrees C
      and pH 4.0-9.0. The protease relative activity was increased in the presence of
      Ni(2+), Mn(2+), and Cu(2+) to 112%, 113%, and 147% of control, respectively. Pure
      SapHM was also activated by dimethylformamide, dimethyl sulfoxide, Tween 80, and
      urea. The activity of the purified enzyme was completely inhibited by
      phenylmethylsulfonyl fluoride, indicating that it is a serine-type protease. The
      Km and Vmax values were estimated to be 35.7 mg/ml, and 5 * 10(4) U/mg for
      casein. Substrate specificity analysis showed that SapH was active on casein,
      bovine serum albumin, and bovine serum fibrin.

PMID- 26215269
TI  - Building Triketide alpha-Pyrone-Producing Yeast Platform Using Heterologous
      Expression of Sporopollenin Biosynthetic Genes.
AB  - Sporopollenin is a poorly characterized mixed aliphatic and aromatic polymer with
      ester and ether linkages. Recent studies have reported that alpha-pyrone
      polyketide compounds generated by Arabidopsis thaliana, polyketide synthase A
      (PKSA) and tetraketide alpha-pyrone reductase 1 (TKPR1), are previously unknown
      sporopollenin precursors. Here, the yeast Saccharomyces cerevisiae was introduced
      to test potential sporopollenin biosynthetic pathways in vivo. A PKSA/TKPR1 dual
      expressor was generated and various chain-length alkyl alpha-pyrones were
      identified by GC-MS. The growth rate of the strain containing PKSA/TKPR1 appeared
      normal. These results indicate that PKSA/TKPR1-expressing yeast would be a
      starting platform to investigate in vivo sporopollenin metabolism. 

PMID- 26215270
TI  - Antimicrobial Peptide, Lumbricusin, Ameliorates Motor Dysfunction and
      Dopaminergic Neurodegeneration in a Mouse Model of Parkinson's Disease.
AB  - We recently reported that the antimicrobial peptide Lumbricusin (NH2
      RNRRWCIDQQA), isolated from the earthworm, increases cell proliferation in
      neuroblastoma SH-SY5Y cells. Here, we investigated whether Lumbricusin has
      neurotropic activity in mouse neural stem cells (MNSCs) and a protective effect
      in a mouse model of Parkinson's disease (PD). In MNSCs isolated from mouse
      brains, Lumbricusin treatment significantly increased cell proliferation (up to
      12%) and reduced the protein expression of p27(Kip1) through proteasomal protein
      degradation but not transcriptional regulation. Lumbricusin inhibited the 6-OHDA
      induced apoptosis of MNSCs, and also showed neuroprotective effects in a mouse PD
      model, ameliorating the motor impairments seen in the pole, elevated body swing,
      and rotation tests. These results suggest that the Lumbricusin-induced promotion
      of neural cell proliferation via p27(Kip1) degradation has a protective effect in
      an experimental PD model. Thus, the antimicrobial peptide Lumbricusin could
      possibly be developed as a potential therapeutic agent for the treatment of PD. 

PMID- 26215271
TI  - Role of flgA for Flagellar Biosynthesis and Biofilm Formation of Campylobacter
      jejuni NCTC11168.
AB  - The complex roles of flagella in the pathogenesis of Campylobacter jejuni, a
      major cause of worldwide foodborne diarrheal disease, are important. Compared
      with the wild-type, an insertional mutation of the flgA gene (cj0769c)
      demonstrated significant decrease in the biofilm formation of C. jejuni NCTC11168
      on major food contact surfaces, such as polystyrene, stainless steel, and
      borosilicate glass. The flgA mutant was completely devoid of flagella and non
      motile whereas the wild-type displayed the full-length flagella and motility. In
      addition, the biofilm formation of the wild-type was inversely dependent on the
      viscosity of the media. These results support that flagellar-mediated motility
      plays a significant role in the biofilm formation of C. jejuni NCTC11168.
      Moreover, our adhesion assay suggests that it plays an important role during
      biofilm maturation after initial attachment. Furthermore, C. jejuni NCTC11168
      wild-type formed biofilm with a net-like structure of extracellular fiber-like
      material, but such a structure was significantly reduced in the biofilm of the
      flgA mutant. It supports that the extracellular fiber-like material may play a
      significant role in the biofilm formation of C. jejuni. This study demonstrated
      that flgA is essential for flagellar biosynthesis and motility, and plays a
      significant role in the biofilm formation of C. jejuni NCTC11168. 

PMID- 26215272
TI  - Roles of the Peptide Transport Systems and Aminopeptidase PepA in Peptide
      Assimilation by Helicobacter pylori.
AB  - Peptide assimilation in Helicobacter pylori necessitates a coordinated working of
      the peptide transport systems (PepTs) and aminopeptidase (PepA). We found that H.
      pylori hydrolyzes two detector peptides, L-phenylalanyl-L-3-thiaphenylalanine
      (PSP) and L-phenylalanyl-L-2- sulfanilylglycine (PSG), primarily before intake
      and excludes their antibacterial effects, whereas Escherichia coli readily
      transports them with resultant growth inhibition. PSP assimilation by H. pylori
      was inhibited by aminopeptidase inhibitor bestatin, but not by dialanine or
      cyanide-m-chlorophenylhydrazone, contrary to that of E. coli. RT- and qRT-PCR
      analyses showed that H. pylori may express first the PepTs (e.g., DppA and DppB)
      and then PepA. In addition, western blot analysis of PepA suggested that the
      bacterium secretes PepA in response to specific inducers. 

PMID- 26215273
TI  - Quantification of LV function and mass by cardiovascular magnetic resonance:
      multi-center variability and consensus contours.
AB  - BACKGROUND: High reproducibility of LV mass and volume measurement from cine
      cardiovascular magnetic resonance (CMR) has been shown within single centers.
      However, the extent to which contours may vary from center to center, due to
      different training protocols, is unknown. We aimed to quantify sources of
      variation between many centers, and provide a multi-center consensus ground truth
      dataset for benchmarking automated processing tools and facilitating training for
      new readers in CMR analysis. METHODS: Seven independent expert readers,
      representing seven experienced CMR core laboratories, analyzed fifteen cine CMR
      data sets in accordance with their standard operating protocols and SCMR
      guidelines. Consensus contours were generated for each image according to a
      statistical optimization scheme that maximized contour placement agreement
      between readers. RESULTS: Reader-consensus agreement was better than inter-reader
      agreement (end-diastolic volume 14.7 ml vs 15.2-28.4 ml; end-systolic volume 13.2
      ml vs 14.0-21.5 ml; LV mass 17.5 g vs 20.2-34.5 g; ejection fraction 4.2 % vs 4.6
      7.5 %). Compared with consensus contours, readers were very consistent (small
      variability across cases within each reader), but bias varied between readers due
      to differences in contouring protocols at each center. Although larger contour
      differences were found at the apex and base, the main effect on volume was due to
      small but consistent differences in the position of the contours in all regions
      of the LV. CONCLUSIONS: A multi-center consensus dataset was established for the
      purposes of benchmarking and training. Achieving consensus on contour drawing
      protocol between centers before analysis, or bias correction after analysis, is
      required when collating multi-center results.

PMID- 26215274
TI  - Determination of a shear rate threshold for thrombus formation in intracranial
      aneurysms.
AB  - BACKGROUND: Particular intra-aneurysmal blood flow conditions, created naturally
      by the growth of an aneurysm or induced artificially by implantation of a flow
      diverter stent (FDS), can potentiate intra-aneurysmal thrombosis. The aim of this
      study was to identify hemodynamic indicators, relevant to this process, which
      could be used as a prediction of the success of a preventive endovascular
      treatment. METHOD: A cross sectional study on 21 patients was carried out to
      investigate the possible association between intra-aneurysmal spontaneous
      thrombus volume and the dome to neck aspect ratio (AR) of the aneurysm. The
      mechanistic link between these two parameters was further investigated through a
      Fourier analysis of the intra-aneurysmal shear rate (SR) obtained by
      computational fluid dynamics (CFD). This analysis was first applied to 10
      additional patients (4 with and 6 without spontaneous thrombosis) and later to 3
      patients whose intracranial aneurysms only thrombosed after FDS implantation.
      RESULTS: The cross sectional study revealed an association between intra
      aneurysmal spontaneous thrombus volume and the AR of the aneurysm (R(2)=0.67,
      p<0.001). Fourier analysis revealed that in cases where thrombosis occurred, the
      SR harmonics 0, 1, and 2 were always less than 25/s, 10/s, and 5/s, respectively,
      and always greater than these values where spontaneous thrombosis was not
      observed. CONCLUSIONS: Our study suggests the existence of an SR threshold below
      which thrombosis will occur. Therefore, by analyzing the SR on patient specific
      data with CFD techniques, it may be potentially possible to predict whether or
      the intra-aneurysmal flow conditions, after FDS implantation, will become
      prothrombotic.

PMID- 26215275
TI  - The Ashtanga Yoga Hindi Scale: An Assessment Tool Based on Eastern Philosophy of
      Yoga.
AB  - The study imports the concept of Ashtanga Yoga from the eastern philosophy of
      Yoga. There is a major disconnect between theory and data in Indian Psychology.
      Indian Psychology provides a rich theoretical base for understanding optimal
      human functioning. However, the theories have not been tested due to paucity of
      tools. A test developed on Ashtanga Yoga is reported. Data were collected in two
      phases from 550 participants. The data were analyzed using exploratory factor
      analysis. Seven factors were extracted as the theory indicates. Overall
      reliability of the scale was found to be excellent (alpha = 0.88), and the
      criterion-related validity was satisfactory as correlations were found to be 0.46
      and 0.48 (p < 0.01) for Flourishing and SPANE-P, respectively, and -0.22 (p <
      0.01) for SPANE-N.

PMID- 26215276
TI  - Performance on the adult rheumatology in-training examination and relationship to
      outcomes on the rheumatology certification examination.
AB  - OBJECTIVE: The American College of Rheumatology (ACR) Adult Rheumatology In
      Training Examination (ITE) is a feedback tool designed to identify strengths and
      weaknesses in the content knowledge of individual fellows-in-training and the
      training program curricula. We determined whether scores on the ACR ITE, as well
      as scores on other major standardized medical examinations and competency-based
      ratings, could be used to predict performance on the American Board of Internal
      Medicine (ABIM) Rheumatology Certification Examination. METHODS: Between 2008 and
      2012, 629 second-year fellows took the ACR ITE. Bivariate correlation analyses of
      assessment scores and multiple linear regression analyses were used to determine
      whether ABIM Rheumatology Certification Examination scores could be predicted on
      the basis of ACR ITE scores, United States Medical Licensing Examination scores,
      ABIM Internal Medicine Certification Examination scores, fellowship directors'
      ratings of overall clinical competency, and demographic variables. Logistic
      regression was used to evaluate whether these assessments were predictive of a
      passing outcome on the Rheumatology Certification Examination. RESULTS: In the
      initial linear model, the strongest predictors of the Rheumatology Certification
      Examination score were the second-year fellows' ACR ITE scores (beta = 0.438) and
      ABIM Internal Medicine Certification Examination scores (beta = 0.273). Using a
      stepwise model, the strongest predictors of higher scores on the Rheumatology
      Certification Examination were second-year fellows' ACR ITE scores (beta = 0.449)
      and ABIM Internal Medicine Certification Examination scores (beta = 0.276). Based
      on the findings of logistic regression analysis, ACR ITE performance was
      predictive of a pass/fail outcome on the Rheumatology Certification Examination
      (odds ratio 1.016 [95% confidence interval 1.011-1.021]). CONCLUSION: The
      predictive value of the ACR ITE score with regard to predicting performance on
      the Rheumatology Certification Examination supports use of the Adult Rheumatology
      ITE as a valid feedback tool during fellowship training.

PMID- 26215277
TI  - Effects of soy phytoestrogens on pituitary-ovarian function in middle-aged female
      rats.
AB  - The aim of this study was to assess the effects of genistein (G) and daidzein (D)
      on the histological, hormonal, and functional parameters of the pituitary-ovarian
      axis in middle-aged female rats, and to compare these effects with the effects of
      estradiol (E), commonly used in the prevention and treatment of menopausal
      symptoms. Middle-aged (12 month old) Wistar female rats subcutaneously received
      35 mg/kg of G, or 35 mg/kg of D, or 0.625 mg/kg of E every day for 4 weeks. Each
      of the treated groups had a corresponding control group. An intact control group
      was also established. G and D did not change the intracellular protein content
      within gonadotropic and lactotropic cells, but vacuolization was observed in all
      the cell types. In contrast, E caused an inhibition of gonadotropic and
      stimulation of lactotropic cells. Also, ovaries of middle-aged female rats
      exposed to G or D have more healthy primordial and primary follicles and less
      atretic follicles. E treatment in the ovaries had a mostly negative effect, which
      is reflected by the increased number of atretic follicles in all tested classes.
      G and D provoked decrease in CuZnSOD and CAT activity, while E treatment
      increased MnSOD and decreased CuZnSOD and GSHPx activity. All the treatments
      increased serum estradiol and decreased testosterone levels, while D and E
      increased the serum progesterone level. In conclusion, soy phytoestrogens
      exhibited beneficial effects on pituitary-ovarian function in middle-aged female
      rats, as compared to estradiol.

PMID- 26215278
TI  - Management of Cushing's disease: a single-center experience.
AB  - The purpose of this study was to review therapeutic outcomes and comorbidities of
      patients with Cushing's disease (CD) in a single center. We conducted a
      retrospective study of 33 patients with CD undergoing transsphenoidal surgery
      from January 2007 to February 2014 (27 females and 6 males, median age 38 years,
      range 18-71 years). The diagnosis of Cushing's syndrome was established on the
      basis of the patient's history, characteristic clinical features, and laboratory
      data including an elevated 24-h urinary free cortisol level, lack of serum
      cortisol suppression after dexamethasone suppression tests and an elevated
      midnight cortisol level. In 28/33 patients, the tumor was visualized on MR of the
      sellar region, while in 5 it was diagnosed using an inferior petrosal sinus
      sampling. Out of the 33 patients, 10 had macroadenoma and the remaining 23 had
      microadenoma. Twenty-one patients (63.6%) had hypertension, 17 (51.5%)
      dyslipidemia, and 7 (21.2%) had type 2 diabetes or impaired glucose tolerance.
      The median follow-up period was 28 months. Remission after transsphenoidal
      surgery was achieved in 78.8% of patients, while 7 patients failed to achieve
      disease remission. Those patients were treated with second-line treatment
      modalities (second operation, radiotherapy, bilateral adrenalectomy, and/or
      ketoconazole). One patient rejected all the treatment modalities after surgery.
      Cumulative remission after all the treatment modalities was achieved in 87.9%
      patients. Patients with Cushing's disease should be managed in centers with much
      experience due to high patient load. In our Center, the remission of the disease
      has been achieved in 78.8% of the patients following transsphenoidal surgery.
      Multimodal treatment which included radiotherapy and medical treatment led to
      biochemical remission of the disease in 87.9% of patients.

PMID- 26215279
TI  - Preclinical testing of selective Aurora kinase inhibitors on a medullary thyroid
      carcinoma-derived cell line.
AB  - Deregulated expression of the Aurora kinases (Aurora-A, B, and C) is thought to
      be involved in cell malignant transformation and genomic instability in several
      cancer types. Over the last decade, a number of small-molecule inhibitors of
      Aurora kinases have been developed, which have proved to efficiently restrain
      malignant cell growth and tumorigenicity. Regarding medullary thyroid carcinoma
      (MTC), we previously showed the efficacy of a pan-Aurora kinase inhibitor (MK
      0457) in impairing growth and survival of the MTC-derived cell line TT. In the
      present study, we sought to establish if one of the Aurora kinases might
      represent a preferential target for MTC therapy. The effects of selective
      inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on TT cell
      proliferation, apoptosis, cell cycle, and ploidy. The two inhibitors reduced TT
      cell proliferation in a time- and dose-dependent manner, with IC50 of 19.0 +/-
      2.4 nM for MLN8237 and 401.6 +/- 44.1 nM for AZD1152. Immunofluorescence
      experiments confirmed that AZD1152 inhibited phosphorylation of histone H3
      (Ser10) by Aurora-B, while it did not affect Aurora-A autophosphorylation.
      MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations
      required to achieve the maximum antiproliferative effects it also abolished H3
      (Ser10) phosphorylation. Cytofluorimetry experiments showed that both inhibitors
      induced accumulation of cells in G2/M phase and increased the subG0/G1 fraction
      and polyploidy. Finally, both inhibitors triggered apoptosis. We demonstrated
      that inhibition of either Aurora-A or Aurora-B has antiproliferative effects on
      TT cells, and thus it would be worthwhile to further investigate the
      therapeutical potential of Aurora kinase inhibitors in MTC treatment.

PMID- 26215280
TI  - Incidence of gastric cancer among patients with gastric precancerous lesions:
      observational cohort study in a low risk Western population.
AB  - OBJECTIVE: To accurately measure the incidence of gastric cancer among patients
      with gastric precancerous lesions, and to quantify the excess incidence in
      comparison with people with normal mucosa on endoscopy and a general population.
      DESIGN: Population based cohort study. SETTING: Population of Sweden using data
      from its national disease registers. PARTICIPANTS: 405,172 patients who had
      gastric biopsy samples taken for non-malignant indications between 1979 and 2011.
      MAIN OUTCOME MEASURES: Incidence of gastric cancer, reported separately for
      patients with different mucosal changes in biopsy samples. Standardised incidence
      ratios provided estimation of the relative risk, using the general Swedish
      population as reference; and hazard ratios were derived from Cox regression
      modelling for internal comparisons with patients with normal gastric mucosa.
      RESULTS: After excluding the first two years of follow-up, 1599 cases of gastric
      cancer were identified. The annual crude incidence of gastric cancer was 20 * 10(
      5) for those in the normal mucosa group (standardised incidence ratio 1.0), 42 *
      10(-5) for those with minor changes (1.5), 59 * 10(-5) for the gastritis group
      (1.8), 100 * 10(-5) for the atrophic gastritis group (2.8), 129 * 10(-5) for the
      intestinal metaplasia group (3.4), and 263 * 10(-5) for the dysplasia group
      (6.5). Cox regression modelling confirmed that excess risks increased
      monotonically with progressive severity of gastric lesions, with the highest
      hazard ratio of 10.9 (dysplasia versus normal mucosa, 95% confidence interval 7.7
      to 15.4). The increased incidence was stable throughout the follow-up period, and
      the gaps between cumulative incidence curves grew continuously. CONCLUSIONS:
      Among patients who undergo gastroscopy with biopsy for clinical indications,
      approximately 1 in 256 with normal mucosa, 1 in 85 with gastritis, 1 in 50 with
      atrophic gastritis, 1 in 39 with intestinal metaplasia, and 1 in 19 with
      dysplasia will develop gastric cancer within 20 years. These numbers, along with
      cost-benefit analyses, should guide future surveillance policies for these
      particular patient groups.

PMID- 26215281
TI  - Risk assessment as a tool for improving external biosecurity at farm level.
AB  - BACKGROUND: Biosecurity routines at herd level may reduce the probability of
      introduction of disease into the herd, but some measures may be regarded as
      expensive and cumbersome for the farmers. Custom-made measures based on
      individual farm characteristics may aid in improving the actual application of on
      farm biosecurity. The aim of the study was to provide a tool for calculating the
      effects of different biosecurity measures and strategies on the individual farm
      level. A simple model was developed to assess the risk of disease introduction
      and the need for biosecurity measures in individual farms. To illustrate the
      general applicability of the tool, it was applied to theoretical examples of
      Swedish cattle and pig farms and diseases endemic in those animal species in the
      EU, in two scenarios with different between-farm contact patterns. RESULTS: The
      model illustrated that the most important factors affecting the risk, and the
      effect of biosecurity measures such as quarantine routines and protective
      clothing, were the frequency of between-farm contacts and prevalence of the
      disease. The risk of introduction as well as the effect of biosecurity measures
      differed between farm types and disease transmission routes. Adapting contact
      patterns to mitigate a specific disease risk was as important as biosecurity
      measures for some farm types, but the largest effect was seen when combining
      biosecurity measures with more planned contact patterns. CONCLUSIONS: The risk
      assessment model proved useful for illustrating the risk of introduction of
      endemic diseases and the mitigating effect of different biosecurity measures on
      farm level. Model outputs could be used to justify prioritisation of measures or
      adapting contact patterns. The theoretic exercise of adjusting model inputs and
      comparing outputs may help veterinary advisors to understand farm-specific risks
      and motivate farmers to improve biosecurity in their individual farm, as it can
      be tailored to each farmer's needs and preferences.

PMID- 26215282
TI  - Thermodynamic analysis of sol-gel transition of gelatin in terms of water
      activity in various solutions.
AB  - Sol-gel transition of gelatin was analyzed as a multisite stoichiometric reaction
      of a gelatin molecule with water and solute molecules. The equilibrium sol-gel
      transition temperature, Tt , was estimated from the average of gelation and
      melting temperature measured by differential scanning calorimetry. From Tt and
      the melting enthalpy, DeltaHsol , the equilibrium sol-to-gel ratio was estimated
      by the van't Hoff equation. The reciprocal form of the Wyman-Tanford equation,
      which describes the sol-to-gel ratio as a function of water activity, was
      successfully applied to obtain a good linear relationship. From this analysis,
      the role of water activity on the sol-gel transition of gelatin was clearly
      explained and the contributions of hydration and solute binding to gelatin
      molecules were separately discussed in sol-gel transition. The general solution
      for the free energy for gel-stabilization in various solutions was obtained as a
      simple function of solute concentration.

PMID- 26215283
TI  - Studies into the phenolic patterns of different tissues of pineapple (Ananas
      comosus [L.] Merr.) infructescence by HPLC-DAD-ESI-MS (n) and GC-MS analysis.
AB  - In a comprehensive study, more than 60 phenolic compounds were detected in
      methanolic extracts from different tissues of pineapple infructescence by high
      performance liquid chromatography with diode array detection and electrospray
      ionisation multiple-stage mass spectrometry (HPLC-DAD-ESI-MS (n) ) as well as by
      gas chromatography-mass spectrometry (GC-MS). The analytical workflow combining
      both methods revealed numerous compounds assigned for the first time as pineapple
      constituents by their mass fragmentations. Pineapple crown tissue was
      characterised by depsides of p-coumaric and ferulic acid. In contrast, major
      phenolic compounds in pineapple pulp extracts were assigned to diverse S-p
      coumaryl, S-coniferyl and S-sinapyl derivatives of glutathione, N-L-gamma
      glutamyl-L-cysteine and L-cysteine, which were also identified in the peel. The
      latter was additionally characterised by elevated concentrations of p-coumaric,
      ferulic and caffeic acid depsides and glycerides, respectively. Two peel-specific
      cyanidin hexosides were found. Elevated concentrations of isomeric N,N'
      diferuloylspermidines may be a useful tool for the detection of fraudulent peel
      usage for pineapple juice production. Mass fragmentation pathways of
      characteristic pineapple constituents are proposed, and their putative biological
      functions are discussed. 

PMID- 26215284
TI  - Exfoliated MoS2 Sheets and Reduced Graphene Oxide-An Excellent and Fast Anode for
      Sodium-ion Battery.
AB  - Three dimensional (3D) MoS2 nanoflowers are successfully synthesized by
      hydrothermal method. Further, a composite of as prepared MoS2 nanoflowers and rGO
      is constructed by simple ultrasonic exfoliation technique. The crystallography
      and morphological studies have been carried out by XRD, FE-SEM, TEM, HR-TEM and
      EDS etc. Here, XRD study revealed, a composite of exfoliated MoS2 with expanded
      spacing of (002) crystal plane and rGO can be prepared by simple 40 minute of
      ultrasonic treatment. While, FE-SEM and TEM studies depict, individual MoS2
      nanoflowers with an average diameter of 200 nm are uniformly distributed
      throughout the rGO surface. When tested as sodium-ion batteries anode material by
      applying two different potential windows, the composite demonstrates a high
      reversible specific capacity of 575 mAhg(-1) at 100 mAg(-1) in between 0.01 V-2.6
      V and 218 mAhg(-1) at 50 mAg(-1) when discharged in a potential range of 0.4 V
      2.6 V. As per our concern, the results are one of the best obtained as compared
      to the earlier published one on MoS2 based SIB anode material and more
      importantly this material shows such an excellent reversible Na-storage capacity
      and good cycling stability without addition of any expensive additive stabilizer,
      like fluoroethylene carbonate (FEC), in comparison to those in current
      literature.

PMID- 26215286
TI  - "It Wasn't About Being Slim": Understanding Eating Disorders in the Context of
      Abuse.
AB  - This article explores how women understand and experience the relationship
      between physical, sexual, and emotional abuse and the emergence of an eating
      disorder in their lives. The past three decades have seen increased attention to
      the links between abuse and eating disorders; however, the social contexts of
      abuse, the specific emotions involved, and how these might link to an eating
      disorder have not been explored. Through an in-depth interview study with 14
      women, narrative-discursive analysis reveals how socially situated, abuse-related
      emotions, such as shame and self-contempt, can play out in an eating disorder and
      are located within social power relations framed primarily by gender but also by
      race and class. 

PMID- 26215285
TI  - Stopping Preemptive Antiviral Therapy for Hepatitis B Virus Can Be Considered for
      Patients with Favorable Predictors.
AB  - BACKGROUND: Preemptive antiviral therapy is recommended for chronic hepatitis B
      virus (HBV)-infected patients receiving cytotoxic chemotherapy. However, little
      data are available for the stopping therapy. AIMS: We evaluated clinical outcome
      and predictors of off-treatment virological response of patients who discontinued
      therapy. METHODS: Ninety-five adult patients who discontinued therapy were
      enrolled. They were analyzed for sustained off-treatment virological response,
      defined as HBV DNA levels below 2000 IU/ml for at least 12 months after the end
      of therapy. RESULTS: Sustained off-treatment virological response was seen in 52
      patients (54.7%). The baseline HBV DNA level was an independent factor associated
      with sustained off-treatment virological response, and the rate was 72.1 and
      23.5% for those with HBV DNA < 2000 IU/ml and >= 2000 IU/ml, respectively (P <
      0.001). The duration of consolidation treatment showed marginal association with
      sustained off-treatment virological response [odd ratio (95% confidence interval)
      1.20 (0.98-1.47), P = 0.069] for those with baseline HBV DNA < 2000 IU/ml, but
      not for those with >= 2000 IU/ml. The sustained off-treatment virological
      response rate was 54.5, 71.4, 73.9, and 100% for consolidation treatment duration
      of <3, 3-6, 6-12, and >= 12 months, respectively, among those with baseline HBV
      DNA < 2000 IU/ml. CONCLUSIONS: The baseline HBV DNA level was indicator for
      sustained off-treatment virological response after stopping preemptive antiviral
      therapy. Consolidation treatment duration showed association with sustained off
      treatment virological response only for those with low baseline HBV DNA levels.

PMID- 26215287
TI  - Violence Against Women: Globalizing the Integrated Ecological Model.
AB  - Globalization theories have proliferated over the past two decades. However,
      global developments have yet to be systematically incorporated into theories
      around violence against women. This article proposes to add a global level to the
      existing ecological model framework, popularized by Lori Heise in 1998, to
      explore the relationships between global processes and experiences of violence
      against women. Data from the Maldives and Cambodia are used to assess how
      globalized ideologies, economic development and integration, religious
      fundamentalisms, and global cultural exchange, as components of a larger
      globalization process, have affected men and women's experiences and perceptions
      of violence against women. 

PMID- 26215289
TI  - Destroying lignocellulosic matters for enhancing methane production from excess
      sludge.
AB  - A lot of lignocellulosic matters are usually present in excess sludge, which are
      hardly degraded in anaerobic digestion (AD) and thus remains mostly in digested
      sludge. This is a reason why the conversion rate of sludge organics into energy
      (CH4) is often low. Obviously, the hydrolysis of AD cannot destruct the structure
      of lignocellulosic matters. Structural destruction of lignocellulosic matters has
      to be performed in AD. In this study, pretreatments with the same principles as
      cell disintegration of sludge were applied to destruct lignocellulosic matters so
      that these materials could be converted to CH4 via AD. Acid, alkali, thermal
      treatment and ultrasonic were used in the experiments to observe the
      destructed/degraded efficiency of lignocellulosic matters. Thermal treatment was
      found to be the most effective pretreatment. Under optimized conditions (T = 150 
      degrees C and t = 30  min), pretreated sludge had a degraded rate of 52.6% in AD,
      due to easy destruction and/or degradation of hemicelluloses and celluloses in
      pretreatment. The sludge pretreated by thermal treatment could enhance the CH4
      yield (mL CH4 g(-1) VSS) by 53.6% compared to raw sludge. Economically, the
      thermal treatment can balance the input energy with the produced energy (steam
      and electricity).

PMID- 26215288
TI  - Potential protective properties of flax lignan secoisolariciresinol diglucoside.
AB  - Lignans are a group of phytonutrients which are widely distributed in the plant
      kingdom. Flaxseed is the richest source of providing lignan precursor such as
      secoisolariciresinol diglucoside (SDG). This article reviews the studies relevant
      to experimental models in animals and humans demonstrating the possible
      nutraceutical actions of SDG to prevent and alleviate lifestyle-related diseases.
      A local and international web-based literature review for this project was
      carried out to provide information relating to the study. The major key word
      "SDG" was selected to gather information using the electronic databases
      pertaining to the current state of flaxseed lignans composition, bioactive
      compounds, metabolism and to find out their role in terms of chemopreventive
      action. The extraction methods vary from simple to complex depending on
      separation, fractionation, identification and detection of the analytes. The
      majority of studies demonstrate that SDG interferes with the development of
      different types of diseases like cardiovascular, diabetic, lupus nephritis, bone,
      kidney, menopause, reproduction, mental stress, immunity, atherosclerosis,
      hemopoietic, liver necrosis and urinary disorders due to its various biological
      properties including anti-inflammatory, antioxidant, antimutagenic,
      antimicrobial, antiobesity, antihypolipidemic and neuroprotective effects.
      Moreover, SDG has a defending mediator against various cancers by modulating
      multiple cell signaling pathways. As discussed in this review, SDG has shown
      therapeutic potential against a number of human diseases and can be recommended
      for discerning consumers. 

PMID- 26215290
TI  - Time to unsafe sexual practice among cross-border female sex workers in Metemma
      Yohannes, North West Ethiopia.
AB  - BACKGROUND: Because of the nature of their work, female sex workers are at risk
      of sexually transmitted diseases. Cross-border areas are places where this
      situation becomes worse. In Ethiopia, there has been a serious scarcity of
      studies on the time at which unsafe sexual practice starts and on factors which
      determine the practice among female sex workers there. Therefore, this study
      aimed to fill this identified gap. METHOD: A total of 467 women who had been sex
      workers at least for three months prior to the resumption of the study were
      included. A structured and pre-tested questionnaire was used to collect data from
      July-August, 2010. Descriptive statistics was used to explore the data, and the
      Extended Cox-Regression model was employed to identify the predictors of time-to
      unsafe sexual practice. RESULT: The study participants were followed for 6, 643
      person-months. The overall incidence density of unsafe sexual practice was 44.71
      persons per 1000 persons-months. The hazard of unsafe sexual practice increased
      by 3.0 % every month (p-value =0.040) due to problem-drinking. Those female sex
      workers with familiarized clients had a two-fold hazard of practicing unsafe sex
      compared to their counterparts (AHR = 1.94 95 % CI 1.49, 2.53). The predominant
      sexual client type and the work place of sex workers were the other significant
      predictors of unsafe sexual practice. CONCLUSIONS: The incidence of unsafe sexual
      practice was found to be high among sex workers in the cross-border area. Time-to
      unsafe sexual practice was significantly associated with female sex workers'
      status of familiarity with their clients, predominant sexual client type, their
      work place, and the interaction term of time and problem-drinking. Interventions
      need to be made on these controllable social and behavioral characteristics to
      help sex workers extend the duration of their safe sexual practice beyond the
      time they will quit sex work.

PMID- 26215292
TI  - Atherosclerosis at your fingertips?

PMID- 26215291
TI  - Remote magnetic navigation vs. manual navigation for ablation of ventricular
      tachycardia: a meta-analysis.
AB  - BACKGROUND: The purpose of this study was to prospectively evaluate the efficacy
      and safety of remote magnetic navigation (RMN) in comparison with manual catheter
      navigation (MCN) in performing ventricular tachycardia ablation. METHODS: An
      electronic search was performed using PubMed (1948-2013) and EMBASE (1974-2013)
      studies comparing RMN with MCN which were published prior to 31 December 2013.
      Outcomes of interest were as follows: acute success, recurrence rate,
      complications, total procedure and fluoroscopic times. Standard mean difference
      (SMD) and its 95 % confidence interval (CI) were used for continuous outcomes;
      odds ratios (OR) were reported for dichotomous variables. RESULTS: Four non
      randomised studies, including a total of 328 patients, were identified. RMN was
      deployed in 191 patients. Acute success and long-term freedom from arrhythmias
      were not significantly different between the RMN and control groups (OR 1.845, 95
      % CI 0.731-4.659, p = 0.195 and OR 0.676, 95 % CI 0.383-1.194, p = 0.177,
      respectively). RMN was associated with less peri-procedural complications (OR
      0.279, 95 % CI 0.092-0.843, p = 0.024). Shorter procedural and fluoroscopy times
      were achieved (95 % CI -0.487 to -0.035, p = 0.024 and 95 % CI -1.467 to -0.984,
      p<0.001, respectively). CONCLUSION: The acute and long-term success rates for VT
      ablation are equal between RMN and MCN, whereas the RMN-guided procedure can be
      performed with a lower complication rate and less procedural and fluoroscopic
      times. More prospective randomised trials will be needed to better evaluate the
      superior role of RMN for catheter ablation of ventricular tachycardia.

PMID- 26215293
TI  - Impact of Smoking and Excess Body Weight on Overall and Site-Specific Cancer
      Mortality Risk.
AB  - BACKGROUND: Smoking and excess body weight are major preventable risk factors for
      premature death. This study aimed at analyzing their single and combined
      association with site-specific cancer mortality. METHODS: Our study population
      comprised 35,784 men and women of ages 14 to 99 years, who participated in
      population-based health surveys conducted 1977-1993 in Switzerland and were
      followed up for mortality until 2008. Multivariable Cox proportional hazards
      models were calculated for different cancer sites, and population attributable
      fractions were derived. RESULTS: The hazard ratio of dying from cancer (all
      sites) was 2.32 (95% confidence interval, 2.04-2.63) for heavy smokers (vs. never
      smokers) and 1.15 (1.01-1.32) for obese [body mass index (BMI) >= 30 kg/m(2)] vs.
      normal weight individuals. Heavy smoking (>=20 cigarettes/day) was associated
      with increased mortality due to cancer of the lung, upper aero-digestive tract,
      pancreas, bladder, liver, and the total of remaining sites. Obesity was
      associated with higher risk of dying from cancer of the liver and the female
      genital tract (essentially corpus or cervix uteri and ovary). More than 20% of
      all cancer deaths in our population were attributable to ever smoking and
      overweight (BMI >= 25 kg/m(2)). CONCLUSIONS: Smoking was a much stronger risk
      factor for cancer than excess body weight. For lung, liver, and pancreatic
      cancer, the combination of excess body weight and smoking lead to cumulated
      higher risks. IMPACT: Our findings support recommendations for obese persons to
      quit smoking despite potential postcessation weight gain.

PMID- 26215295
TI  - Ecological Change and Aging: A Need to Think Deeply and Act Quickly.

PMID- 26215296
TI  - Spirituality and Aging in Place: The Impact of Extreme Climatic Conditions on
      Domestic Gardening Practice.
AB  - There is limited research exploring how domestic water restrictions imposed as a
      result of drought conditions impact upon the lives of independently living older
      people. Within this age group (60 years plus), the domestic garden frequently
      forms an intrinsic component of ongoing health and well-being. Gardening practice
      offers components of both mental and physical activity and, for many older
      people, leads to emotional and spiritual connection on a number of levels. The
      capacity of older people to maintain a garden during a period of water
      restrictions is greatly reduced, and the resulting impact on health and well
      being is considerable. A recent study, conducted in south-eastern Australia,
      aimed to determine the benefits to health and well-being of maintaining a
      domestic garden for older people and the impact of water restrictions on garden
      practice. This occurred at a time following a prolonged period of drought and, in
      central Victoria, a complete ban on outside watering. In-depth qualitative
      interviews were conducted with 10 gardeners aged between 60 and 83 who had tended
      their garden over an extended period. The lived experience of gardening was
      explored through hermeneutic phenomenological analysis. Clear benefits to health
      and well-being were established, and yet, the essence of this experience lay in
      the capacity of gardeners to remain connected to their garden despite change. The
      crisis imposed by ongoing drought and restricted use of water generated a strong
      impetus for adaptation, resilience and acceptance of change. The spiritual nature
      of gardening practice clearly emerged and appeared to intensify the experience of
      gardening and consolidate adaption to change on a number of levels. 

PMID- 26215294
TI  - Time Trends in Rates of Hodgkin Lymphoma Histologic Subtypes: True Incidence
      Changes or Evolving Diagnostic Practice?
AB  - BACKGROUND: Histologic subtypes of classical Hodgkin lymphoma [cHL; e.g., nodular
      sclerosis, mixed cellularity, not otherwise specified (NOS)] are
      epidemiologically and prognostically distinctive. Therefore, unexplained, ongoing
      incidence rate declines for mixed cellularity and increases for NOS require
      examination. METHODS: We analyzed detailed histology-specific Hodgkin lymphoma
      incidence rates in 1992 through 2011 U.S. SEER data (n = 21,372) and reviewed a
      regional subset of 2007 through 2011 NOS pathology reports for insight into
      diagnostic practices. RESULTS: cHL rates were stable until 2007, then decreased
      for whites [annual percent change (APC) and 95% confidence interval (CI), -3.6% (
      5.6% to -1.5%)]. Nodular sclerosis rates declined after 2007 by 5.9% annually,
      with variation by gender, age, and race/ethnicity. In 1992 through 2011, mixed
      cellularity rates declined [APC -4.0% (-4.7% to -3.3%)], whereas NOS rates rose
      [5.3% (4.5%-6.2%)] overall and in most patient groups. The 2007-2011 NOS age
      specific rates were more similar to mixed cellularity rates for 1992-1996 than
      2007-2011. Trends in combined rates were minimal, supporting increasing
      misclassification of mixed cellularity, lymphocyte depletion, and specific
      nodular sclerosis subtypes as NOS. Eighty-eight of 165 reviewed NOS pathology
      reports addressed classification choice. Twenty (12.1%) justified the
      classification, 21 (12.7%) described insufficient biopsy material, and coders
      missed specific subtype information for 27 (16.4%). CONCLUSION: Recent nodular
      sclerosis rate declines largely represent true incidence changes. Long-term rate
      decreases for mixed cellularity and other less common subtypes, and increases for
      NOS (comprising ~30% of cHL cases in 2011), likely reflect changes in diagnostic
      and/or classification practice. IMPACT: Diminishing histologic subtyping
      undermines future surveillance and epidemiologic study of Hodgkin lymphoma.
      Guideline-based use of excisional biopsies and more coding quality control are
      warranted.

PMID- 26215297
TI  - Intergenerational Efforts to Develop a Healthy Environment for Everyone:
      Sustainability as a Human Rights Issue.
AB  - As climate change proceeds at an unprecedented rate, concern for the natural
      environment has increased. The world's population aging also continues to rise at
      an unprecedented rate, giving greater attention to the implications of an older
      population. The two trends are linked through the fact that changes to the
      environment affect older adults, and older adults affect the environment.
      Sustainability is, therefore, an intergenerational phenomenon, and protecting
      resources today leaves a positive legacy and enhances quality of life for future
      generations. Older adults have much to share with younger generations about
      behaviors that promote sustainable living, yet few sustainability efforts are
      intergenerational in nature. As large numbers of people currently subsist without
      secure access to basic needs, ensuring equitable resource consumption for all
      generations is urgent and aligns with the Universal Declaration of Human Rights.
      Through exploring linkages between aging and sustainability, we identify
      intergenerational strategies to protect the environment and promote human rights
      and quality of life for older adults. 

PMID- 26215298
TI  - Older Adults' Current and Potential Uses of Information Technologies in a
      Changing World: A Theoretical Perspective.
AB  - Technologies have become a major force in people's lives. They change how people
      interact with the environment, even as the environment changes. We propose that
      technology use in the setting of changing environments is motivated by essential
      needs and tensions experienced by the individual. We apply three developmental
      and behavioral theories (Erikson's stages of psychosocial development, Maslow's
      hierarchy of needs, and Bronfenbrenner's ecological model) to explain technology
      related behaviors among older adults. We consider how technology use has
      addressed and can address major ecological changes, in three areas: health
      promotion, natural disasters, and disparities. We propose that considering these
      theories can help researchers and developers ensure that technologies will help
      promote a healthier world for older adults. 

PMID- 26215299
TI  - Overcoming Objections by Elders to Action on Climate Change.

PMID- 26215300
TI  - Understanding Resistance to Climate Change Resistance.
AB  - Fifty years after the emergence of warnings over the effects of the environmental
      impacts of industrialization and other conditions of a planet subjugated by
      humans, we are still entertaining discussions about the existence of the
      phenomena of climate change. Worse still, we have not checked the behaviors and
      conditions that exacerbate the rate of environmental destruction. Older people,
      particularly those who are economically vulnerable, are among those most at risk
      in disasters, including events resulting from climate change. By applying the
      "epistemologies of ignorance" outlined by Nancy Tuana, I attempt to understand
      the rooted ignorance that prevents acceptance of the environmental impact of
      human kind's unrepentant misuse of the world's natural resources and the refusal
      to curb the excesses that have lead to environmental damage that has had, and
      that will continue to have, dire consequences on the planet and for the most
      vulnerable denizens of Earth. Far from being a pessimistic project of abjection
      and despair, this article proposes that an examination of climate change denial
      can provide guidance for the development of a better counter-narrative. 

PMID- 26215301
TI  - Gray Is Green Presence at People's Climate March.

PMID- 26215302
TI  - Healthy Environments Across Generations=Healthy Aging.

PMID- 26215303
TI  - Public Justice: Emphasizing the Social in Health and the Health in Social.

PMID- 26215304
TI  - GABA diffusion across neuronal columns for efficient sensory tuning.
AB  - Synaptic (phasic) lateral inhibition between neuronal columns mediated by
      GABAergic interneurons is, in general, essential for primary sensory cortices to
      respond selectively to elemental features. We propose here a neural network model
      with a nonsynaptic (tonic) lateral inhibitory mechanism. While firing,
      intrasynaptic GABA molecules spill over into extracellular space and accumulate
      in neuronal columns. Through accumulation in and diffusion across these columns,
      a level of ambient (extracellular) GABA changes in a neuronal activity-dependent
      manner. Ambient GABA molecules act on extrasynaptic receptors and provide neurons
      with tonic inhibitory currents. We examined whether and how the diffusion of GABA
      molecules across neuronal columns affects tuning performance of the network to a
      feature stimulus: selective responsiveness. The GABA diffusion led to reducing
      ambient GABA in the stimulus-relevant column while augmenting ambient GABA in
      stimulus-irrelevant columns, thereby improving the tuning performance. The GABA
      diffusion was effective especially when provided with a broader sensory input.
      Interestingly, this diffusion-based, nonsynaptic (tonic) lateral inhibitory
      scheme worked well together with the conventional, synaptic (phasic) lateral
      inhibitory scheme, enhancing the sensory tuning. We suggest that the nonsynaptic
      lateral inhibition, mediated through GABA diffusion across neuronal columns, may
      be beneficial for the cortex to tune to sensory features. 

PMID- 26215306
TI  - Compliance Measurements of the Upper Airway in Pediatric Down Syndrome Sleep
      Apnea Patients.
AB  - Compliance of soft tissue and muscle supporting the upper airway are two of
      several factors contributing to pharyngeal airway collapse. We present a novel,
      minimally invasive method of estimating regional variations in pharyngeal
      elasticity. Magnetic resonance images for pediatric sleep apnea patients with
      Down syndrome [9.5 +/- 4.3 years (mean age +/- standard deviation)] were analyzed
      to segment airways corresponding to baseline (no mask pressure) and two positive
      pressures. A three dimensional map was created to evaluate axial and
      circumferential variation in radial displacements of the airway, dilated by the
      positive pressures. The displacements were then normalized with respect to the
      appropriate transmural pressure and radius of an equivalent circle to obtain a
      measure of airway compliance. The resulting elasticity maps indicated the least
      and most compliant regions of the pharynx. Airway stiffness of the most compliant
      region [403 +/- 204 (mean +/- standard deviation) Pa] decreased with severity of
      obstructive sleep apnea. The non-linear response of the airway wall to continuous
      positive airway pressure was patient specific and varied between anatomical
      locations. We identified two distinct elasticity phenotypes. Patient phenotyping
      based on airway elasticity can potentially assist clinical practitioners in
      decision making on the treatments needed to improve airway patency.

PMID- 26215307
TI  - Influence of Geometry and Mechanical Properties on the Accuracy of Patient
      Specific Simulation of Women Pelvic Floor.
AB  - The woman pelvic system involves multiple organs, muscles, ligaments, and fasciae
      where different pathologies may occur. Here we are most interested in abnormal
      mobility, often caused by complex and not fully understood mechanisms. Computer
      simulation and modeling using the finite element (FE) method are the tools
      helping to better understand the pathological mobility, but of course patient
      specific models are required to make contribution to patient care. These models
      require a good representation of the pelvic system geometry, information on the
      material properties, boundary conditions and loading. In this contribution we
      focus on the relative influence of the inaccuracies in geometry description and
      of uncertainty of patient-specific material properties of soft connective
      tissues. We conducted a comparative study using several constitutive behavior
      laws and variations in geometry description resulting from the imprecision of
      clinical imaging and image analysis. We find that geometry seems to have the
      dominant effect on the pelvic organ mobility simulation results. Provided that
      proper finite deformation non-linear FE solution procedures are used, the
      influence of the functional form of the constitutive law might be for practical
      purposes negligible. These last findings confirm similar results from the fields
      of modeling neurosurgery and abdominal aortic aneurysms. 

PMID- 26215305
TI  - New insights into the architecture of the islet of Langerhans: a focused cross
      species assessment.
AB  - The human genome project and its search for factors underlying human diseases has
      fostered a major human research effort. Therefore, unsurprisingly, in recent
      years we have observed an increasing number of studies on human islet cells,
      including disease approaches focusing on type 1 and type 2 diabetes. Yet, the
      field of islet and diabetes research relies on the legacy of rodent-based
      investigations, which have proven difficult to translate to humans, particularly
      in type 1 diabetes. Whole islet physiology and pathology may differ between
      rodents and humans, and thus a comprehensive cross-species as well as species
      specific view on islet research is much needed. In this review we summarise the
      current knowledge of interspecies islet cytoarchitecture, and discuss its
      potential impact on islet function and future perspectives in islet
      pathophysiology research. 

PMID- 26215308
TI  - Computational Modeling of Healthy Myocardium in Diastole.
AB  - In order to better understand the mechanics of the heart and its disorders,
      engineers increasingly make use of the finite element method (FEM) to investigate
      healthy and diseased cardiac tissue. However, FEM is only as good as the
      underlying constitutive model, which remains a major challenge to the
      biomechanics community. In this study, a recently developed structurally based
      constitutive model was implemented to model healthy left ventricular myocardium
      during passive diastolic filling. This model takes into account the orthotropic
      response of the heart under loading. In-vivo strains were measured from magnetic
      resonance images (MRI) of porcine hearts, along with synchronous catheterization
      pressure data, and used for parameter identification of the passive constitutive
      model. Optimization was performed by minimizing the difference between MRI
      measured and FE predicted strains and cavity volumes. A similar approach was
      followed for the parameter identification of a widely used phenomenological
      constitutive law, which is based on a transversely isotropic material response.
      Results indicate that the parameter identification with the structurally based
      constitutive law is more sensitive to the assigned fiber architecture and the fit
      between the measured and predicted strains is improved with more realistic sheet
      angles. In addition, the structurally based model is capable of generating a more
      physiological end-diastolic pressure-volume relationship in the ventricle. 

PMID- 26215309
TI  - Cardiac Extracellular Matrix Scaffold Generated Using Sarcomeric Disassembly and
      Antigen Removal.
AB  - Xenogeneic cardiac extracellular matrix (cECM) scaffolds for reconstructive
      cardiac surgery applications have potential to overcome the limitations of
      current clinically utilized patch materials. A potentially ideal cECM scaffold
      would be immunologically acceptable while preserving the native cECM niche.
      Production of such a scaffold necessitates removal of cellular and antigenic
      components from cardiac tissue while preserving cECM structure/function
      properties. Existing decellularization methodologies predominantly utilize
      denaturing detergents which might irreversibly alter cECM material properties. To
      overcome potential deficiencies of current approaches, the effect of sarcomere
      relaxation and disassembly on resultant cECM scaffold cellularity was
      investigated. Additionally, the ability of sequential differential protein
      solubilization (antigen removal-AR) to reduce cECM scaffold antigenicity was
      examined. Sarcomeric relaxation and disassembly were necessary to achieve
      scaffold acellularity. All groups in which AR was employed displayed
      statistically significant decreases in residual antigenicity regardless of their
      degree of acellularity. AR combined with sarcomeric disassembly preserved
      structural, biochemical, mechanical and recellularization properties of the cECM
      scaffold. However, sodium dodecyl sulfate significantly altered cECM properties.
      This study demonstrates the importance of solubilizing cellular elements and
      antigenic components in a stepwise manner for production of a potentially ideal
      cECM scaffold and may have implications for future tissue engineering and
      regenerative medicine applications. 

PMID- 26215311
TI  - Health-related quality of life and aerobic fitness in people with schizophrenia.
AB  - The purpose of this cross-sectional study was to investigate whether aerobic
      fitness contributes to the health-related quality of life (HRQoL) in people with
      schizophrenia, while adjusting for other previously-established contributory
      factors. Thirty-four male (34.1 +/- 12.0 years) and 13 female (34.3 +/- 9.2
      years) participants performed a submaximal Astrand-Rhyming cycle ergometer test
      and completed the 36-item Short-Form Health Survey, the International Physical
      Activity Questionnaire, and the Psychosis Evaluation tool for Common Use by
      Caregivers. After controlling for age and sex, illness duration (12.4 +/- 11.2
      years, r(2) = 0.38, P < 0.001), fewer positive (9.3 +/- 4.3, r(2) = 0.30, P =
      0.006) and cognitive (8.4 +/- 3.8, r(2) = 0.28, P = 0.011) symptoms, and higher
      aerobic fitness (34.5 +/- 8.7 ml O2  min(-1) kg(-1), r(2) = 0.36, P = 0.001) were
      found to be independent significant predictors of physical HRQoL (mean score 66.6
      +/- 18.5). However, when all variables were included in the same regression
      model, only illness duration (P = 0.004) and positive symptoms (P = 0.045)
      remained significant predictors, while there was a trend (P < 0.10) for age and
      aerobic fitness. The final model explained 54% of the variability in physical
      HRQoL. No significant correlates for mental HRQoL (54.9 +/- 18.5) were found.
      People with schizophrenia might improve their physical HRQoL by improving their
      aerobic fitness. Mental health nurses should assist in facilitating improvements
      in aerobic fitness through facilitating physical activity participation in
      patients with schizophrenia.

PMID- 26215310
TI  - Molecular characterization and primary functional analysis of PeMPEC, a magnesium
      protoporphyrin IX monomethyl ester cyclase gene of bamboo (Phyllostachys edulis).
AB  - KEY MESSAGE: A homologous gene of MPEC from Phyllostachys edulis was isolated and
      characterized. Its overexpression in Arabidopsis thaliana increased chlorophyll
      concentration and photosynthesis efficiency, indicating it is involved in
      chlorophyll biosynthesis. Magnesium-protoporphyrin IX monomethyl ester cyclase
      (MPEC) is an essential enzyme in the biosynthesis of chlorophyll, which plays an
      important role in photosynthesis. However, limited information is available on
      the roles of MPEC gene in bamboo. A homologous gene, PeMPEC was identified from
      Phyllostachys edulis, which comprised 1474 bp and contained an open reading frame
      encoding 415 amino acids. PeMPEC was transcribed abundantly in leaf blade where
      photosynthesis predominantly occurs, which agreed with the protein accumulation
      pattern confirmed by Western blotting. The PeMPEC transcription was promoted by
      continuous darkness for 24 h, and was suppressed by increasing light intensity
      (100-1500 umo1 m(-2) s(-1)) and high temperature (42  degrees C). However,
      transcription was induced within 0.5 h and thereafter declined with prolonged
      treatment (up to 12 h) under low temperature (4  degrees C). Although PeMPEC
      expressed weakly in etiolated leaves, transcript levels increased gradually with
      subsequent light treatment (200 umol m(-2) s(-1)). Overexpression of PeMPEC in
      Arabidopsis thaliana resulted in increased chlorophyll concentration and
      photosynthesis efficiency in sense transgenic plants compared with a reduction in
      antisense transgenic plants. These changes were consistent with the transcript
      levels of PeMPEC. These results indicated that PeMPEC might be involved in
      chlorophyll biosynthesis and play important roles in maintaining the stability of
      photosystems, and provide a basis for the study of chlorophyll biosynthesis and
      dissection of photosynthesis in bamboo.

PMID- 26215312
TI  - The 1-h oral glucose tolerance test glucose and insulin values are associated
      with markers of clinical deterioration in cystic fibrosis.
AB  - AIMS: Cystic fibrosis (CF) is associated with the emergence of CF-related
      diabetes (CFRD). CFRD is associated with increased risk of accelerated weight
      and/or lung function loss (clinical degradation). Data in the CF pediatric
      population reported an association between higher 60-min oral glucose tolerance
      test (OGTT) plasma glucose values and reduced lung function. Our objective was to
      evaluate the relationship between the 60-min OGTT insulin and glucose values and
      markers of clinical degradation in adult patients with CF. METHODS: This study
      was based on an ongoing observational cohort of CF adult patients (>=18 years).
      All patients underwent a 2-h OGTT with 30-min interval sample measurements.
      Plasma insulin and glucose levels were measured. Adult patients (N = 240) were
      categorized based on the 60-min OGTT median values of glucose (G60, 11.0 mmol/L)
      and/or insulin (I60, 43.4 MUU/mL). RESULTS: A negative association was observed
      between the 60-min OGTT glucose value and pulmonary function (FEV1; P = 0.001),
      whereas 60-min OGTT insulin values were positively associated with BMI (P =
      0.004). Patients with high G60 values displayed lower FEV1 than patients with low
      G60 values (P = 0.025). Patients with higher I60 values demonstrated higher
      values of both FEV1 (P = 0.022) and BMI (P = 0.003) than patients with low I60
      values. More importantly, when adjusting for BMI, the difference in FEV1 between
      both groups no longer existed (P = 0.166). CONCLUSIONS: Both insulin and glucose
      values at 60-min OGTT are associated with indicators of clinical degradation in
      adult patients with CF. Future prospective analyses are essential in establishing
      the clinical utility of these indicators.

PMID- 26215313
TI  - Junctional rhythm during hypoglycaemic encephalopathy.

PMID- 26215314
TI  - Spirituality, quality of life, psychological adjustment in terminal cancer
      patients in hospice.
AB  - The purpose of this study was to show the different components of spirituality in
      the last few weeks of life for advanced cancer patients admitted to hospice and
      to evaluate quality of life (QoL), pain, anxiety, depression and psychological
      adjustment to cancer. One hundred and fifteen patients were interviewed with a
      series of rating scales: the Functional Assessment of Chronic Illness Therapy -
      Spiritual Well-Being Scale, the Hospital Anxiety and Depression Scale, the Visual
      Analogue Scale for pain, the Brief Coping Orientation to Problem Experienced and
      the Functional Assessment of Cancer Therapy Scale - General Measure. Workers and
      single patients with higher education level showed a worse QoL. Moreover, anxiety
      and pain were negatively associated with QoL, while spirituality and
      'Instrumental Support' coping style were positively associated with QoL. In the
      Italian sample, it was observed that when patients are close to death, faith is a
      more important component of spirituality than meaning/peace. This study confirms
      that QoL could be related to physical and psychological symptoms, and this
      reiterates the importance of faith in end-of-life care.

PMID- 26215315
TI  - Phosphorescent Platinum(II) Complexes with C^C* Cyclometalated NHC Dibenzofuranyl
      Ligands: Impact of Different Binding Modes on the Decay Time of the Excited
      State.
AB  - Two C^C* cyclometalated platinum(II) N-heterocyclic carbene (NHC) complexes with
      the general formula [(C^C*)Pt(O^O)] (C^C*=1-dibenzofuranyl-3
      methylbenzimidazolylidene; O^O=dimesitoylmethane) have been synthesized and
      extensively characterized, including solid-state structure determination, (195)
      Pt NMR spectroscopy, and 2D NMR (COSY, HSQC, HMBC, NOESY) spectroscopy to
      elucidate the impact of their structural differences. The two regioisomers differ
      in the way the dibenzofuranyl (DBF) moiety of the NHC ligand is bound to the
      metal center, which induces significant changes in their physicochemical
      properties, especially on the decay time of the excited state. Quantum yields of
      over 80 % and blue emission colors were measured. 

PMID- 26215316
TI  - Gene-expression analysis of cementoblasts and osteoblasts.
AB  - BACKGROUND AND OBJECTIVE: Cementum and bone are similar mineralized tissues, but
      cementum accumulates much more slowly than bone, does not have vasculature or
      innervation and does not undergo remodeling. Despite these differences, there are
      no well-established markers to distinguish cementoblasts from other mature
      mineralizing cells such as osteoblasts and odontoblasts. The purpose of this
      study was to assess differences in gene expression between cementoblasts and
      osteoblasts using gene profiling of cell populations isolated directly from
      osteocalcin-green fluorescent protein (OC-GFP) transgenic mice. MATERIAL AND
      METHODS: OC-GFP reporter mice were used as they show labeling of cementoblasts,
      osteoblasts and odontoblasts, but not of periodontal ligament fibroblasts, within
      the periodontium. We sorted cells digested from the molar root surface to isolate
      OC-GFP(+) cementoblasts. Osteoblasts were isolated from calvarial digests.
      Microarray analysis was performed, and selected results were confirmed by real
      time PCR and immunostaining or in situ hybridization. RESULTS: Microarray
      analysis identified 95 genes that were expressed at least two-fold higher in
      cementoblasts than in osteoblasts. Our analysis indicated that the Wnt signaling
      pathway was differentially regulated, as were genes related to skeletal
      development. Real-time PCR confirmed that expression of the Wnt inhibitors Wnt
      inhibitory factor 1 (Wif1) and secreted frizzled-related protein 1 (Sfrp1) was
      elevated in cementoblasts compared with osteoblasts, and Wif1 expression was
      localized to the apical root region. In addition, the transcription factor BARX
      homeobox 1 (Barx1) was expressed at higher levels in cementoblasts, and
      immunohistochemistry indicated that BARX1 was expressed in apical cementoblasts
      and cementocytes, but not in osteoblasts or odontoblasts. CONCLUSION: The OC-GFP
      mouse provides a good model for selectively isolating cementoblasts, and allowed
      for identification of differentially expressed genes between cementoblasts and
      osteoblasts.

PMID- 26215317
TI  - Mason type II and III radial head fracture in patients older than 65: is there
      still a place for radial head resection?
AB  - PURPOSE: To evaluate the clinical outcomes of radial head excision for
      multifragmentary radial head fracture in patients over 65 years old. METHODS: We
      retrospectively examined 30 patients over 65 years of age treated with radial
      head excision for comminuted radial head fractures. Patients were evaluated
      through clinical examinations, administrative questionnaires (DASH--Disabilities
      of the Arm, Shoulder and Hand; MEPS--Mayo Elbow Performance Score, VAS--Visual
      Analog Scale) and plain films. RESULTS: The mean follow-up was 40 months (range
      24-72 months); 27 out of 30 patients claimed to be satisfied. The mean DASH score
      was 13 (range 3-45.8) and mean MEPS was 79 (range 65-97). The radiographic
      evaluation showed 21 cases of elbow arthritis; only two of them complained about
      pain. Heterotopic ossification was evident in six cases with functional
      impairment in only one patient. Six patients with increased ulnar variance had
      clinical distal radio-ulnar joint instability. DISCUSSION: Radial head excision
      has been considered a safe surgical procedure with satisfactory clinical
      outcomes. Development in biomechanical studies and prosthetic replacement of the
      radial head question the validity of radial head excision. In current literature,
      there are neither long-term follow-up studies on radial head prosthesis outcomes
      nor studies which consider elderly patient samples. CONCLUSION: Radial head
      resection remains a good option when a radial head fracture occurs in elderly
      patients, taking into account the influence of poor bone quality and
      comorbidities on the outcome. Radial head excision is not indicated in the
      presence of associated lesions, because of the risk of residual elbow
      instability; complications associated with advanced age must be considered and a
      strict follow-up granted.

PMID- 26215318
TI  - Clinical characteristics of population referred to an Italian center for
      dementia: an update.

PMID- 26215319
TI  - Prenatal exposure to common environmental factors affects brain lipids and
      increases risk of developing autism spectrum disorders.
AB  - The prevalence of autism spectrum disorders (ASDs) has been on the rise over
      recent years. The presence of diverse subsets of candidate genes in each
      individual with an ASD and the vast variability of phenotypical differences
      suggest that the interference of an exogenous environmental component may greatly
      contribute to the development of ASDs. The lipid mediator prostaglandin E2 (PGE2
      ) is released from phospholipids of cell membranes, and is important in brain
      development and function; PGE2 is involved in differentiation, synaptic
      plasticity and calcium regulation. The previous review already described
      extrinsic factors, including deficient dietary supplementation, and exposure to
      oxidative stress, infections and inflammation that can disrupt signaling of the
      PGE2 pathway and contribute to ASDs. In this review, the structure and
      establishment of two key protective barriers for the brain during early
      development are described: the blood-brain barrier; and the placental barrier.
      Then, the first comprehensive summary of other environmental factors, such as
      exposure to chemicals in air pollution, pesticides and consumer products, which
      can also disturb PGE2 signaling and increase the risk for developing ASDs is
      provided. Also, how these exogenous agents are capable of crossing the protective
      barriers of the brain during critical developmental periods when barrier
      components are still being formed is described. This review underlines the
      importance of avoiding or limiting exposure to these factors during vulnerable
      periods in development.

PMID- 26215320
TI  - Calycosin induces apoptosis by the regulation of ERbeta/miR-17 signaling pathway
      in human colorectal cancer cells.
AB  - Prior studies have suggested that a high intake of isoflavonoids is associated
      with a protective effect against hormone-related cancers, such as colorectal
      cancer (CRC). Calycosin, a main component of isoflavones, has been shown to
      suppress the growth of hormone-dependent tumors through an ERbeta-mediated
      signaling pathway. However, the effects of calycosin on CRC remain unclear. In
      this study, we aimed to investigate the anti-tumor activities of calycosin on CRC
      and its potential mechanism. HCT-116 cells were treated with calycosin. Cell
      proliferation, apoptosis and invasiveness were measured by MTT assay, flow
      cytometry and transwell invasion assay, respectively. mRNA levels of ER beta
      (ERbeta) and miR-17 were quantified by real-time PCR. Protein expressions of
      ERbeta and phosphatase and tensin homolog deleted on chromosome ten (PTEN) were
      determined by western blotting. We found that calycosin significantly induced
      apoptosis, and inhibited proliferation and invasiveness of HCT-116 cells in a
      dose-dependent manner. In addition, ERbeta expression significantly increased in
      calycosin-treated HCT-116 cells, followed by a decrease of miR-17, and up
      regulation of PTEN. Our results indicate that calycosin has an inhibitory effect
      on CRC, which might be obtained by ERbeta-mediated regulation of miR-17 and PTEN
      expression. 

PMID- 26215321
TI  - Comparative efficacy and safety of antidiabetic drug regimens added to stable and
      inadequate metformin and thiazolidinedione therapy in type 2 diabetes.
AB  - AIMS: Determine the efficacy and safety of antidiabetic agents added-on to
      metformin and a thiazolidinedione (TZD) in patients with inadequately controlled
      type 2 diabetes (T2D). METHODS: MEDLINE and CENTRAL were searched for randomised
      controlled trials (RCTs) evaluating the addition of an antidiabetic agent in
      patients with T2D inadequately controlled on stable, optimised metformin and TZD
      therapy (>= 1500 mg metformin and >= 50% maximum TZD dose for >= 4 weeks).
      Frequentist network meta-analysis was performed on identified studies. RESULTS:
      Eleven RCTs evaluating dipeptidyl peptidase-4 inhibitors (linagliptin,
      sitagliptin), sulfonylureas (SUs) (glibenclamide, glimepiride), glucagon-like
      peptide-1 (GLP-1) analogues (exenatide, liraglutide, dulaglutide, taspoglutide)
      and sodium-glucose cotransporter2 (SGLT2) inhibitors (canagliflozin,
      empagliflozin) were identified. The mean reduction in HbA1c from baseline was
      significant for all agents (range, 0.55-1.17%) vs. placebo. SUs were associated
      with weight gain (range, 3.31-7.29 kg), while weight loss was seen with all GLP-1
      analogues (range, 1.53-2.20 kg) and SGLT2 inhibitors (range, 2.08-2.95 kg) vs.
      placebo. Relative risk of hypoglycaemia was increased with dulaglutide, exenatide
      and glimepiride vs. placebo (RR range, 2.65-6.17); and trended higher with all
      other agents except linagliptin. GLP-1 analogues and canagliflozin reduced
      systolic blood pressure vs. placebo (range, 2.39-5.05 mmHg). No agent with
      available data increased the risk of urinary or genital tract infection vs.
      placebo. CONCLUSION: When added to stable, optimised metformin and TZD, all
      evaluated antidiabetic agents reduced HbA1c; albeit not to the same degree.
      Moreover, agents differed in their effects on body weight, hypoglycaemia and
      systolic blood pressure.

PMID- 26215322
TI  - Ti(3+) Aqueous Solution: Hybridization and Electronic Relaxation Probed by State
      Dependent Electron Spectroscopy.
AB  - The electronic structure of a Ti(3+) aqueous solution is studied by liquid-jet
      soft X-ray photoelectron (PE) spectroscopy. Measured valence and Ti 2p core-level
      binding energies, together with the Ti 2p resonant photoelectron (RPE) spectra
      and the derived partial electron-yield L-edge X-ray absorption (PEY-XA) spectra,
      reveal mixing between metal 3d and water orbitals. Specifically, ligand states
      with metal character are identified through the enhancement of signal intensities
      in the RPE spectra. An observed satellite 3d peak structure is assigned to
      several different metal-ligand states. Experimental energies and the delocalized
      nature of the respective orbitals are supported by ground-state electronic
      structure calculations. We also show that by choice of the detected Auger
      electron-decay channel, from which different PEY-XA spectra are obtained, the
      experimental sensitivity to the interactions of the metal 3d electrons with the
      solvent can be varied. The effect of such a state-dependent electronic relaxation
      on the shape of the PEY-XA spectra is discussed in terms of different degrees of
      electron delocalization. 

PMID- 26215324
TI  - Ramucirumab, another anti-angiogenic agent for metastatic colorectal cancer in
      second-line setting--its impact on clinical practice.
AB  - The recent FDA approval of ramucirumab (RAISE trial) has added a third agent to
      our existing armamentarium of angiogenesis inhibitors (bevacizumab and ziv
      aflibercept) for the second-line treatment of metastatic colorectal cancer, which
      may have some impacts in the current clinic practice. 

PMID- 26215323
TI  - Associations of coffee consumption with markers of liver injury in the insulin
      resistance atherosclerosis study.
AB  - BACKGROUND: Coffee consumption has been associated with reduced risk of
      developing type 2 diabetes mellitus (T2DM) however, the mechanism for this
      association has yet to be elucidated. Non-alcoholic fatty liver disease (NAFLD)
      characterizes and predicts T2DM yet the relationship of coffee with this disorder
      remains unclear. Our aim was to investigate the associations of coffee with
      markers of liver injury in 1005 multi-ethnic, non-diabetic adults in the Insulin
      Resistance Atherosclerosis Study. METHODS: Dietary intake was assessed using a
      validated 114-item food frequency questionnaire. Alanine aminotransferase (ALT),
      aspartate aminotransferase (AST) and fetuin-A were determined in fasting blood
      samples and the validated NAFLD liver fat score was calculated. Multivariate
      linear regression assessed the contribution of coffee to variation in markers of
      liver injury. RESULTS: Caffeinated coffee showed significant inverse associations
      with ALT (beta = -0.08, p = 0.0111), AST (beta = -0.05, p = 0.0155) and NAFLD
      liver fat score (beta = -0.05, p = 0.0293) but not with fetuin-A (beta = 0.04, p
      = 0.17). When the highest alcohol consumers were excluded, these associations
      remained (ALT beta = -0.11, p = 0.0037; AST beta = -0.05, p = 0.0330; NAFLD liver
      fat score beta = -0.06, p = 0.0298). With additional adjustment for insulin
      sensitivity, the relationship with ALT remained significant (ALT beta = -0.08, p
      = 0.0400; AST beta = -0.03, p = 0.20; NAFLD liver fat score beta = -0.03, p =
      0.27). There were no significant associations of decaffeinated coffee with liver
      markers. CONCLUSIONS: These analyses indicate a beneficial impact of caffeinated
      coffee on liver morphology and/or function, and suggest that this relationship
      may mediate the well-established inverse association of coffee with risk of T2DM.

PMID- 26215325
TI  - A survey on the developmental intestinal microbiota research in China: The
      history, funding, and frontiers of gut bacteria.
AB  - Up to 100 trillion bacteria are harbored in the human intestine with a
      mutualistic and interdependent relationship with the host during a long period of
      co-evolution. The so-called intestinal microbiota (IM) fulfill important
      metabolic tasks and the impaired stability may lead to IM-related diseases,
      including inflammatory bowel disease (IBD), colorectal cancer (CRC), metabolic
      syndrome (MS), liver diseases, and so on. Here, we review the past and
      development of IM research in China, including the achievements that Chinese
      researchers have made both in basic and clinical scientific field. Moreover, we
      evaluate the contributions of the National Natural Science Foundation of China
      (NSFC), the 973 National Basic Research Program of China (973 Program), the 863
      National High Technology Research and Development Program of China (863 Program),
      and funds from the public health industry in the field of IM research. 

PMID- 26215326
TI  - Does the clinical presentation of a prior preterm birth predict risk in a
      subsequent pregnancy?
AB  - OBJECTIVE: The objective of the study was to determine whether risk of recurrent
      preterm birth differs based on the clinical presentation of a prior spontaneous
      preterm birth (SPTB): advanced cervical dilatation (ACD), preterm premature
      rupture of membranes (PPROM), or preterm labor (PTL). STUDY DESIGN: This
      retrospective cohort study included singleton pregnancies from 2009 to 2014
      complicated by a history of prior SPTB. Women were categorized based on the
      clinical presentation of their prior preterm delivery as having ACD, PPROM, or
      PTL. Risks for sonographic short cervical length and recurrent SPTB were compared
      between women based on the clinical presentation of their prior preterm birth.
      Log-linear regression was used to control for confounders. RESULTS: Of 522
      patients included in this study, 96 (18.4%) had prior ACD, 246 (47.1%) had prior
      PPROM, and 180 (34.5%) had prior PTL. Recurrent PTB occurred in 55.2% of patients
      with a history of ACD compared with 27.2% of those with PPROM and 32.2% with PTL
      (P = .001). The mean gestational age at delivery was significantly lower for
      those with a history of ACD (34.0 weeks) compared with women with prior PPROM
      (37.2 weeks) or PTL (37.0 weeks) (P = .001). The lowest mean cervical length
      prior to 24 weeks was significantly shorter in patients with a history of
      advanced cervical dilation when compared with the other clinical presentations.
      CONCLUSION: Patients with a history of ACD are at an increased risk of having
      recurrent preterm birth and cervical shortening in a subsequent pregnancy
      compared with women with prior preterm birth associated PPROM or PTL.

PMID- 26215327
TI  - Magnetic resonance imaging of acute appendicitis in pregnancy: a 5-year
      multiinstitutional study.
AB  - OBJECTIVE: The purpose of this study was to determine the diagnostic performance
      of magnetic resonance imaging (MRI) in the diagnosis of acute appendicitis during
      pregnancy in a multiinstitutional study. STUDY DESIGN: In this multicenter
      retrospective study, the cases of pregnant women who underwent MRI evaluation of
      abdominal or pelvic pain and who had clinical suspicion of acute appendicitis
      between June 1, 2009, and July 31, 2014, were reviewed. All MRI examinations with
      positive findings for acute appendicitis were confirmed with surgical pathologic
      information. Sensitivity, specificity, negative predictive values, and positive
      predictive values were calculated. Receiver operating characteristic curves were
      generated, and area under the curve analysis was performed for each participating
      institution. RESULTS: Of the cases that were evaluated, 9.3% (66/709) had MRI
      findings of acute appendicitis. Sensitivity, specificity, accuracy, positive
      predictive value, and negative predictive values were 96.8%, 99.2%, 99.0%, 92.4%,
      and 99.7%, respectively. There was no statistically significant difference
      between centers that were included in the study (pair-wise probability values
      ranged from 0.12-0.99). CONCLUSION: MRI is useful and reproducible in the
      diagnosis of suspected acute appendicitis during pregnancy.

PMID- 26215328
TI  - Depletion of polymorphonuclear leukocytes has no effect on preterm delivery in a
      mouse model of Escherichia coli-induced labor.
AB  - OBJECTIVE: The objective of the study was to investigate the role of
      polymorphonuclear leukocytes (PMNs) in a mouse model of Escherichia coli-induced
      labor. STUDY DESIGN: Intraperitoneal injection of rabbit antimouse PMN antiserum
      or control was performed in CD-1 mice 29 hours and 5 hours prior to laparotomy
      and intrauterine injection of either killed E coli or phosphate-buffered saline
      on day 14.5 of pregnancy. Preterm delivery was defined as delivery of at least 1
      pup within 48 hours. Circulating leukocyte counts were determined manually or by
      flow cytometry at the time of surgery and 8, 24, and 48 hours afterward. Maternal
      and fetal tissues were analyzed in a separate group of animals 8 hours after
      surgery. RESULTS: Pretreatment with anti-PMN antiserum significantly decreased
      the numbers of circulating leukocytes and the proportion of neutrophils among all
      leukocytes by 70-80% at surgery and at least 8 hours thereafter. Neutrophil
      depletion significantly reduced 2 markers of neutrophil activation in the uterus
      and placenta (neutrophil elastase and myeloperoxidase activity) and neutrophil
      infiltration into gestational tissues in bacterially treated animals to baseline
      (control) levels but did not affect preterm birth rates. The large E coli-induced
      increases in uterine inflammatory markers (interleukin-1beta, tumor necrosis
      factor, chemokine ligand-5, cyclooxygenase-2) were not affected or were only
      minimally affected by neutrophil depletion. CONCLUSION: Although PMN antiserum
      reduces both neutrophil number and activity, it does not diminish sensitivity to
      bacterially induced delivery or meaningfully alter the expression of inflammatory
      markers in the mouse model. Preterm birth and inflammation in this model are not
      likely to depend on neutrophil function.

PMID- 26215329
TI  - Urolithiasis in pregnancy: a cost-effectiveness analysis of ureteroscopic
      management vs ureteral stenting.
AB  - OBJECTIVE: The purpose of this study was to determine the cost-effectiveness of
      serial stenting vs ureteroscopy for treatment of urolithiasis during pregnancy as
      a function of gestational age (GA) at diagnosis. STUDY DESIGN: We built decision
      analytic models for a hypothetical cohort of pregnant women who had received a
      diagnosis of symptomatic ureteral calculi and compared serial stenting to
      ureteroscopy. We assumed ureteral stent replacement every 4 weeks during
      pregnancy, intravenous sedation for stent placement, and spinal anesthetic for
      ureteroscopy. Outcomes were derived from the literature and included stent
      infection, migration, spontaneous kidney stone passage, ureteral injury, failed
      ureteroscopy, postoperative urinary tract infection, sepsis, and anesthetic
      complications. Four separate analyses were run based on the GA at diagnosis of
      urolithiasis. Using direct costs and quality-adjusted life years, we reported the
      incremental costs and effectiveness of each strategy based on GA at kidney stone
      diagnosis and calculated the net monetary benefit. We performed 1-way and Monte
      Carlo sensitivity analyses to assess the strength of the model. RESULTS:
      Ureteroscopy was less costly and more effective for urolithiasis, irrespective of
      GA at diagnosis. The incremental cost of ureteroscopy increased from -$74,469 to 
      $7631, and the incremental effectiveness decreased from 0.49 to 0.05 quality
      adjusted life years for a kidney stone diagnosed at 12 and 36 weeks of gestation,
      respectively. The net monetary benefit of ureteroscopy progressively decreased
      for kidney stones that were diagnosed later in pregnancy. The model was robust to
      all variables. CONCLUSION: Ureteroscopy is less costly and more effective
      relative to serial stenting for urolithiasis, regardless of the GA at diagnosis.
      Ureteroscopy is most beneficial for women who received the diagnosis early during
      pregnancy.

PMID- 26215330
TI  - The association between maternal antioxidant levels in midpregnancy and
      preeclampsia.
AB  - OBJECTIVE: We sought to determine whether midpregnancy antioxidant levels are
      associated with preeclampsia, overall and by timing of onset. STUDY DESIGN: We
      carried out a case-control study, nested within a cohort of 5337 pregnant women
      in Montreal, Quebec, Canada. Blood samples obtained at 24-26 weeks were assayed
      for nonenzymatic antioxidant levels among cases of preeclampsia (n = 111) and
      unaffected controls (n = 441). We excluded women diagnosed with gestational
      hypertension only. We used logistic regression with the z-score of each
      antioxidant level as the main predictor variable for preeclampsia risk. We
      further stratified early-onset (<34 weeks) and late-onset preeclampsia and
      carried out multinomial logistic regression. Finally, we assessed associations
      between antioxidant biomarkers and timing of onset (in weeks) by Cox regression,
      with appropriate selection weights. We summed levels of correlated biomarkers
      (r(2) > 0.3) and log-transformed positively skewed distributions. We adjusted for
      body mass index, nulliparity, preexisting diabetes, hypertension, smoking, and
      proxies for ethnicity and socioeconomic status. RESULTS: The odds ratios for
      alpha-tocopherol, alpha-tocopherol:cholesterol, lycopene, lutein, and carotenoids
      (sum of alpha-carotene, beta-carotene, anhydrolutein, alpha-cryptoxanthin, and
      beta-cryptoxanthin) suggested an inverse association between antioxidant levels
      and overall preeclampsia risk; however, only lutein was significantly associated
      with overall preeclampsia in adjusted models (odds ratio, 0.60; 95% confidence
      interval, 0.46-0.77) per SD. In multinomial logistic models, the relative risk
      ratio (RRR) estimates for the early-onset subgroup were farther from the null
      than those for the late-onset subgroup. The ratio of alpha-tocopherol to
      cholesterol and retinol were significantly associated with early- but not late
      onset preeclampsia: RRRs (95% confidence intervals) for early-onset preeclampsia
      0.67 (0.46-0.99) and 1.61 (1.12-2.33), respectively. Lutein was significantly
      associated with both early- and late-onset subtypes in adjusted models; RRRs 0.53
      (0.35-0.80) and 0.62 (0.47-0.82), respectively. Survival analyses confirmed these
      trends. CONCLUSION: Most antioxidants were more strongly associated with early
      onset preeclampsia, suggesting that oxidative stress may play a greater role in
      the pathophysiology of early-onset preeclampsia. Alternatively, reverse causality
      may explain this pattern. Lutein was associated with both early- and late-onset
      preeclampsia and may be a promising nutrient to consider in preeclampsia
      prevention trials, if this finding is corroborated.

PMID- 26215331
TI  - Simultaneous left ventricular assist device placement and laparoscopic sleeve
      gastrectomy as a bridge to transplant for morbidly obese patients with severe
      heart failure.

PMID- 26215332
TI  - Creatine supplementation attenuates pulmonary and systemic effects of lung
      ischemia and reperfusion injury.
AB  - BACKGROUND: Creatine (Cr) is a dietary supplement that presents beneficial
      effects in experimental models of heart and brain ischemia and reperfusion (I/R)
      injury. It can improve adenosine 5'-triphosphate generation and reduce cell
      damage. This study evaluated the effects of Cr supplementation in a model of lung
      I/R. METHODS: Forty male Wistar rats were divided into 4 groups: sham operated,
      Cr+sham, I/R, and Cr+I/R. We investigated the effects of 5 days of Cr
      supplementation (0.5 g/kg/day by gavage) before left pulmonary artery ischemia
      (90 minutes) and reperfusion (120 minutes) on pulmonary and systemic response.
      RESULTS: Cr inhibited the I/R-induced increase in exhaled nitric oxide (p <
      0.05), total cells (p < 0.01), and neutrophils (p < 0.001) in bronchoalveolar
      lavage fluid and in the systemic circulation (p < 0.001). The levels of
      interleukin-1beta (p < 0.05), tissue damping, and tissue elastance (p < 0.05)
      were also minimized. Cr also inhibited pulmonary edema formation (total proteins
      in bronchoalveolar lavage fluid, p < 0.001; histologic edema index, p < 0.001)
      and neutrophils accumulation in lung tissue (p < 0.001). As possible mechanisms
      underlying Cr effects, we observed a reduced expression of caspase 3 (p < 0.05),
      reduced expression of Toll-like receptor (TLR) 4, and increased expression of
      TLR7 in lung tissue (p < 0.001). CONCLUSIONS: Cr supplementation presents
      pulmonary and systemic protective effects in acute lung injury induced by I/R in
      rats. These beneficial effects seem to be related to the anti-inflammatory and
      anti-oxidant properties of Cr and modulation of TLRs.

PMID- 26215333
TI  - Clinical utility of invasive exercise hemodynamic evaluation in LVAD patients.

PMID- 26215334
TI  - Prevalence and characterization of Chlamydia DNA in zoo animals in Japan.
AB  - Because many people visit zoos, prevention of zoonoses is important from the
      standpoint of public health. This study examined the prevalence of Chlamydia
      among zoo animals in Japan by PCR and characterized these bacteria by performing
      phylogenetic analyses of the sequences of the variable domain (VD) 2 and VD4
      regions of the ompA gene, which encodes the Chlamydia major outer membrane
      protein. Fecal samples were collected from 1150 zoo animals in five zoos and
      examined for Chlamydia DNA. Chlamydia psittaci DNA was found in 3.9% of mammals,
      7.2% of birds and 8.1% of reptiles. The prevalence of Chlamydia pneumoniae DNA
      was significantly higher in reptiles (5.8%) than in mammals (0.3%) and birds
      (0.3%). Phylogenetic analysis of the ompA VD2 region from 18 samples showed that
      nine were in three different clusters containing C. psittaci strains, six were in
      a cluster containing C. pneumoniae strains and three each formed a distinct
      branch. Furthermore, phylogenetic analysis of the ompA VD4 region showed that C.
      pneumoniae DNAs from reptiles were close to those from human patients. The C.
      pneumoniae DNAs from the European glass lizard, Emerald tree boa, and Panther
      chameleon were classified in clusters that were distinct from other strains,
      suggesting that these reptiles had each been infected with a specific C.
      pneumoniae genotype. This study showed that diverse Chlamydia strains have been
      prevalent among a variety of zoo animals.

PMID- 26215335
TI  - Point-of-care testing for respiratory viruses in adults: The current landscape
      and future potential.
AB  - Respiratory viruses are responsible for a large proportion of acute respiratory
      illness in adults as well as children, and are associated with a huge socio
      economic burden worldwide. Development of accurate point-of-care tests (POCT) for
      respiratory viruses has been listed as a priority by the World Health
      Organisation and replacing the current paradigm of empirical antimicrobial use
      with directed use is a listed goal of the movement for reduction in antimicrobial
      resistance. POCTs for respiratory viruses have previously been limited by the
      poor sensitivity of antigen detection based tests and by a limited range of
      detectable viruses. Highly accurate molecular platforms are now able to test for
      a comprehensive range of viruses, can be operated by non-laboratory staff and can
      generate a result in approximately 1 h, making them potentially deployable as
      POCTs. The potential clinical benefits of POC testing for respiratory viruses in
      adults include a reduction in unnecessary antibiotic use, improved antiviral
      prescribing for influenza and rationalisation of isolation facilities. We review
      here the burden of disease, the currently available molecular platforms with
      potential for POCT use and the existing evidence for clinical and economic
      benefits of testing for respiratory viruses in adults. 

PMID- 26215336
TI  - Myocardial Iron Loading Assessment by Automatic Left Ventricle Segmentation with
      Morphological Operations and Geodesic Active Contour on T2* images.
AB  - Myocardial iron loading thalassemia patients could be identified using T2*
      magnetic resonance images (MRI). To quantitatively assess cardiac iron loading,
      we proposed an effective algorithm to segment aligned free induction decay
      sequential myocardium images based on morphological operations and geodesic
      active contour (GAC). Nine patients with thalassemia major were recruited (10
      male and 16 female) to undergo a thoracic MRI scan in the short axis view. Free
      induction decay images were registered for T2* mapping. The GAC were utilized to
      segment aligned MR images with a robust initialization. Segmented myocardium
      regions were divided into sectors for a region-based quantification of cardiac
      iron loading. Our proposed automatic segmentation approach achieve a true
      positive rate at 84.6% and false positive rate at 53.8%. The area difference
      between manual and automatic segmentation was 25.5% after 1000 iterations.
      Results from T2* analysis indicated that regions with intensity lower than 20 ms
      were suffered from heavy iron loading in thalassemia major patients. The proposed
      method benefited from abundant edge information of the free induction decay
      sequential MRI. Experiment results demonstrated that the proposed method is
      feasible in myocardium segmentation and was clinically applicable to measure
      myocardium iron loading.

PMID- 26215337
TI  - The achievement of public health services in pharmacy practice: A literature
      review.
AB  - BACKGROUND: It is known that pharmacists are currently contributing to public
      health; however, the extent of this contribution as reported in the literature
      has not been examined. Investigating the ways that pharmacists are currently
      participating in public health is critical for the profession of pharmacy,
      pharmacy educators, and the public health community. OBJECTIVES: The purpose of
      this study was to determine the reported contributions of pharmacy to each of the
      ten essential services of public health, and which of the five core competencies
      of public health were most frequently utilized in those contributions. METHODS: A
      PubMed search was used to extract references that included both the words
      pharmacy and services in the title or abstract, and the words public health in
      any part of the document. A total of 247 references were extracted and
      categorized into the essential services and core competencies. RESULTS: The
      essential services Inform, Educate, and Empower, and Link to/Provide Care were
      more frequently represented in the literature, and the core competency of Health
      Policy and Administration was most frequently utilized. CONCLUSION: To further
      contribute to and integrate their contributions within population health,
      pharmacists must consider ways to strategically contribute to the essential
      services of public health and seek to increase competency in public health.

PMID- 26215338
TI  - A novel thermostable GH5_7 beta-mannanase from Bacillus pumilus GBSW19 and its
      application in manno-oligosaccharides (MOS) production.
AB  - A novel thermostable mannanase from a newly isolated Bacillus pumilus GBSW19 has
      been identified, expressed, purified and characterized. The enzyme shows a
      structure comprising a 28 amino acid signal peptide, a glycoside hydrolase family
      5 (GH5) catalytic domain and no carbohydrate-binding module. The recombinant
      mannanase has molecular weight of 45 kDa with an optimal pH around 6.5 and is
      stable in the range from pH 5-11. Meanwhile, the optimal temperature is around 65
      degrees C, and it retains 50% relative activity at 60  degrees C for 12h. In
      addition, the purified enzyme can be activated by several ions and organic
      solvents and is resistant to detergents. Bpman5 can efficiently convert locus
      bean gum to mainly M2, M3 and M5, and hydrolyze manno-oligosaccharides with a
      minimum DP of 3. Further exploration of the optimum condition using HPLC to
      prepare oligosaccharides from locust bean gum was obtained as 10mg/ml locust bean
      gum incubated with 10 U/mg enzyme at 50  degrees C for 24h. By using this enzyme,
      locust bean gum can be utilized to generate high value-added oligosaccharides
      with a DP of 2-6.

PMID- 26215339
TI  - Ethanol induced astaxanthin accumulation and transcriptional expression of
      carotenogenic genes in Haematococcus pluvialis.
AB  - Haematococcus pluvialis is one of the most promising natural sources of
      astaxanthin. However, inducing the accumulation process has become one of the
      primary obstacles in astaxanthin production. In this study, the effect of ethanol
      on astaxanthin accumulation was investigated. The results demonstrated that
      astaxanthin accumulation occurred with ethanol addition even under low-light
      conditions. The astaxanthin productivity could reach 11.26 mg L(-1) d(-1) at 3%
      (v/v) ethanol, which was 2.03 times of that of the control. The transcriptional
      expression patterns of eight carotenogenic genes were evaluated using real-time
      PCR. The results showed that ethanol greatly enhanced transcription of the
      isopentenyl diphosphate (IPP) isomerase genes (ipi-1 and ipi-2), which were
      responsible for isomerization reaction of IPP and dimethylallyl diphosphate
      (DMAPP). This finding suggests that ethanol induced astaxanthin biosynthesis was
      up-regulated mainly by ipi-1 and ipi-2 at transcriptional level, promoting
      isoprenoid synthesis and substrate supply to carotenoid formation. Thus ethanol
      has the potential to be used as an effective reagent to induce astaxanthin
      accumulation in H. pluvialis.

PMID- 26215340
TI  - Functional evaluation of residues in the herbicide-binding site of Mycobacterium
      tuberculosis acetohydroxyacid synthase by site-directed mutagenesis.
AB  - Mycobacterium tuberculosis acetohydroxyacid synthase (M. tuberculosis AHAS) has
      been proposed to bean essential target for novel herbicide- and chemical-based
      antibacterial agents. Therefore, here we investigated the roles of multiple
      conserved herbicide-binding site residues (R318, A146, Q148, M512, and V513) in
      M. tuberculosis AHAS through site-directed mutagenesis by characterizing the
      kinetic parameters and herbicide sensitivities of various point mutants.
      Interestingly, all mutant enzymes showed significantly altered kinetic
      parameters, specifically reduced affinity towards both the substrate and
      cofactor. Importantly, mutation of R318 led to a complete loss of AHAS activity,
      indicating a key role for this residue in substrate binding. Furthermore, all
      mutants demonstrated significant herbicide resistance against chlorimuron ethyl
      (CE), with several-fold higher IC50 than that of wild type AHAS. Docking analysis
      also indicated that binding of CE was slightly affected upon mutation of these
      residues. Taken together, these data suggest that the residues examined here
      mediate CE binding and may also be important for the catalytic activity of AHAS.
      This study will pave the way for future structure-function studies of CE and will
      also aid the development of novel anti-tuberculosis agents based on this chemical
      scaffold. 

PMID- 26215341
TI  - Co-production of S-adenosyl-L-methionine and L-isoleucine in Corynebacterium
      glutamicum.
AB  - In this study, production of S-adenosyl-L-methionine in Corynebacterium
      glutamicum was investigated by overexpressing genes metK and vgb. Compared with
      vector control, overexpression of metK alone in C. glutamicum ATCC13032 and
      IWJ001 increased SAM production 5.11 and 11.65 times, respectively; while
      overexpression of metK and vgb in C. glutamicum ATCC13032 and IWJ001 increased
      SAM production 5.83 and 14.95 times, respectively. Further studies on IWJ001/pDXW
      8-metk-vgb showed that the limiting factor for SAM production is intracellular
      ATP supply. Since IWJ001 is an L-isoleucine production strain, IWJ001/pDXW-8-metk
      vgb could produce both SAM and L-isoleucine. After 72 h fermentation, SAM and L
      isoleucine in IWJ001/pDXW-8-metk-vgb reached 0.67 g/L and 13.8 g/L, respectively.
      The results demonstrate the potential application of C. glutamicum for co
      production of SAM and amino acids.

PMID- 26215342
TI  - Continuous hydrolysis of carboxymethyl cellulose with cellulase aggregates
      trapped inside membranes.
AB  - Enzymatic hydrolysis of cellulose is often conducted in batch processes in which
      hydrolytic products tend to inhibit enzyme activity. In this study, we report a
      method for continuous hydrolysis of carboxymethyl cellulose (CMC) by using cross
      linked cellulase aggregate (XCA) trapped inside a membrane. XCA particles
      prepared by using a millifluidic reactor have a uniform size distribution around
      350 nm. Because of their large size, XCA particles in solutions can be filtered
      through a polyethersulfone membrane to collect 87.1 +/- 0.9% of XCA particles.
      The membrane with impregnated XCA can be used as a catalyst for hydrolysis of CMC
      in a continuous mode. When the CMC concentration is 1.0 g/l and the flow rate is
      2 MUl/min, 53.9% of CMC is hydrolyzed to reducing sugars. The membrane with XCA
      is very stable under continuously flowing solutions. After 72 h of reaction,
      97.5% of XCA remains inside the membrane.

PMID- 26215343
TI  - Glucose biosensor based on glucose oxidase immobilized at gold nanoparticles
      decorated graphene-carbon nanotubes.
AB  - Biopolymer pectin stabilized gold nanoparticles were prepared at graphene and
      multiwalled carbon nanotubes (GR-MWNTs/AuNPs) and employed for the determination
      of glucose. The formation of GR-MWNTs/AuNPs was confirmed by scanning electron
      microscopy, X-ray diffraction, UV-vis and FTIR spectroscopy methods. Glucose
      oxidase (GOx) was successfully immobilized on GR-MWNTs/AuNPs film and direct
      electron transfer of GOx was investigated. GOx exhibits highly enhanced redox
      peaks with formal potential of -0.40 V (vs. Ag/AgCl). The amount of electroactive
      GOx and electron transfer rate constant were found to be 10.5 * 10(-10) mol cm(
      2) and 3.36 s(-1), respectively, which were significantly larger than the
      previous reports. The fabricated amperometric glucose biosensor sensitively
      detects glucose and showed two linear ranges: (1) 10 MUM - 2 mM with LOD of 4.1
      MUM, (2) 2 mM - 5.2 mM with LOD of 0.95 mM. The comparison of the biosensor
      performance with reported sensors reveals the significant improvement in overall
      sensor performance. Moreover, the biosensor exhibited appreciable stability,
      repeatability, reproducibility and practicality. The other advantages of the
      fabricated biosensor are simple and green fabrication approach, roughed and
      stable electrode surface, fast in sensing and highly reproducible.

PMID- 26215344
TI  - A yeast co-culture-based biosensor for determination of waste water contamination
      levels.
AB  - Artificial microbial co-cultures were formed to develop the receptor element of a
      biosensor for assessment of biological oxygen demand (BOD). The co-cultures
      possessed broad substrate specificities and enabled assays of water and
      fermentation products within a broad BOD range (2.4-80 mg/dm(3)) with a high
      correlation to the standard method (R = 0.9988). The use of the co-cultures of
      the yeasts Pichia angusta, Arxula adeninivorans and Debaryomyces hansenii
      immobilized in N-vinylpyrrolidone-modified poly(vinyl alcohol) enabled developing
      a BOD biosensor possessing the characteristics not inferior to those in the known
      biosensors. The results are indicative of a potential of using these co-cultures
      as the receptor element base in prototype models of instruments for broad
      application.

PMID- 26215345
TI  - Modulating the regioselectivity of a Pasteurella multocida sialyltransferase for
      biocatalytic production of 3'- and 6'-sialyllactose.
AB  - Several bacterial sialyltransferases have been reported to be multifunctional
      also catalysing sialidase and trans-sialidase reactions. In this study, we
      examined the trans-sialylation efficacy and regioselectivity of mutants of the
      multifunctional Pasteurella multocida sialyltransferase (PmST) for catalysing the
      synthesis of 3'- and 6'-sialyllactose using casein glycomacropeptide as sialyl
      donor and lactose as acceptor. The mutation P34H led to a 980-fold increase in
      alpha-2,6-sialyltransferase activity (with cytidine-5'-monophospho-N
      acetylneuraminic acid as donor), while its alpha-2,3-sialyltransferase activity
      was abolished. Histidine in this position is conserved in alpha-2,6
      sialyltransferases and has been suggested, and recently confirmed, to be the
      determinant for strict regiospecificity in the sialyltransferase reaction. Our
      data verified this theorem. In trans-sialidase reactions, the P34H mutant
      displayed a distinct preference for 6'-sialyllactose synthesis but low levels of
      3'-sialyllactose were also produced. The sialyllactose yield was however lower
      than when using PmSTWT under optimal conditions for 6'-sialyllactose formation.
      The discrepancy in regiospecificity between the two reactions could indicate
      subtle differences in the substrate binding site in the two reactions. In
      contrast, the two mutations E271F and R313Y led to preferential synthesis of 3'
      sialyllactose over 6'-sialyllactose and the double mutant (PmSTE271F/R313Y)
      exhibited the highest alpha-2,3-regioselectivity via reduced sialidase and alpha
      2,6-trans-sialidase activity. The double mutant PmSTE271F/R313Y thus showed the
      highest alpha-2,3-regioselectivity and constitutes an interesting enzyme for
      regioselective synthesis of alpha-2,3-sialylated glycans. This study has expanded
      the understanding of the structure-function relationship of multifunctional,
      bacterial sialyltransferases and provided new enzymes for regioselective glycan
      sialylation. 

PMID- 26215346
TI  - Novel thermophilic hemicellulases for the conversion of lignocellulose for second
      generation biorefineries.
AB  - The biotransformation of lignocellulose biomasses into fermentable sugars is a
      very complex procedure including, as one of the most critical steps, the (hemi)
      cellulose hydrolysis by specific enzymatic cocktails. We explored here, the
      potential of stable glycoside hydrolases from thermophilic organisms, so far not
      used in commercial enzymatic preparations, for the conversion of glucuronoxylan,
      the major hemicellulose of several energy crops. Searches in the genomes of
      thermophilic bacteria led to the identification, efficient production, and
      detailed characterization of novel xylanase and alpha-glucuronidase from
      Alicyclobacillus acidocaldarius (GH10-XA and GH67-GA, respectively) and a alpha
      glucuronidase from Caldicellulosiruptor saccharolyticus (GH67-GC). Remarkably,
      GH10-XA, if compared to other thermophilic xylanases from this family, coupled
      good specificity on beechwood xylan and the best stability at 65  degrees C (3.5
      days). In addition, GH67-GC was the most stable alpha-glucuronidases from this
      family and the first able to hydrolyse both aldouronic acid and aryl-alpha
      glucuronic acid substrates. These enzymes, led to the very efficient hydrolysis
      of beechwood xylan by using 7- to 9-fold less protein (concentrations <0.3 MUM)
      and in much less reaction time (2h vs 12h) if compared to other known
      biotransformations catalyzed by thermophilic enzymes. In addition, remarkably,
      together with a thermophilic beta-xylosidase, they catalyzed the production of
      xylose from the smart cooking pre-treated biomass of one of the most promising
      energy crops for second generation biorefineries. We demonstrated that search by
      the CAZy Data Bank of currently available genomes and detailed enzymatic
      characterization of recombinant enzymes allow the identification of glycoside
      hydrolases with novel and interesting properties and applications.

PMID- 26215347
TI  - Protein engineering of Bacillus acidopullulyticus pullulanase for enhanced
      thermostability using in silico data driven rational design methods.
AB  - Thermostability has been considered as a requirement in the starch processing
      industry to maintain high catalytic activity of pullulanase under high
      temperatures. Four data driven rational design methods (B-FITTER, proline theory,
      PoPMuSiC-2.1, and sequence consensus approach) were adopted to identify the key
      residue potential links with thermostability, and 39 residues of Bacillus
      acidopullulyticus pullulanase were chosen as mutagenesis targets. Single
      mutagenesis followed by combined mutagenesis resulted in the best mutant E518I
      S662R-Q706P, which exhibited an 11-fold half-life improvement at 60  degrees C
      and a 9.5  degrees C increase in Tm. The optimum temperature of the mutant
      increased from 60 to 65  degrees C. Fluorescence spectroscopy results
      demonstrated that the tertiary structure of the mutant enzyme was more compact
      than that of the wild-type (WT) enzyme. Structural change analysis revealed that
      the increase in thermostability was most probably caused by a combination of
      lower stability free-energy and higher hydrophobicity of E518I, more hydrogen
      bonds of S662R, and higher rigidity of Q706P compared with the WT. The findings
      demonstrated the effectiveness of combined data-driven rational design approaches
      in engineering an industrial enzyme to improve thermostability.

PMID- 26215348
TI  - Effect of PFM Firing Cycles on the Mechanical Properties, Phase Composition, and
      Microstructure of Nickel-Chromium Alloy.
AB  - PURPOSE: The purpose of this study was to compare the mechanical properties of
      beryllium-free nickel-chromium (Ni-Cr) dental casting alloy before and after each
      porcelain firing cycle (once fired, twice fired, and thrice fired) and to relate
      these properties to the microstructural changes and changes in X-ray diffraction
      patterns of Ni-Cr alloy that occur after each porcelain firing cycle. MATERIAL
      AND METHODS: Forty tensile bar specimens and 20 disc-shaped specimens of Ni-Cr
      alloy were prepared. These specimens were divided into four groups. The first
      group was not heat treated and tested in the as-cast condition, thus serving as
      control group. The second, third, and fourth groups were fired once, twice, and
      thrice, respectively. Tensile bar specimens were loaded to failure in tension
      using a universal testing machine. Values of ultimate tensile strength, 0.1%
      yield strength, and percentage elongations were determined. Microstructural study
      and hardness testing were done using an optical microscope and digital Vickers
      hardness tester, respectively, on disc-shaped specimens. Disc-shaped specimens
      were again used to obtain the X-ray diffraction patterns by using diffractometer
      Bruker D8 focus. Statistical comparisons of the mechanical properties and
      hardness of the alloy were made with ANOVA. Intergroup comparisons of the data in
      the as-cast and fired specimens were analyzed by applying Tukey's HSD multiple
      comparison tests. RESULTS: Before porcelain firing, the alloy exhibited higher
      ultimate tensile strength (548 MPa), 0.1% yield strength (327 MPa), hardness (192
      HV), and lower elongation values (18%). After each firing cycle, there was a
      significant (p < 0.001) decrease in ultimate strength (464 MPa for three times
      fired specimens), 0.1% yield strength (284 MPa for three times fired group), and
      hardness (164 HV for three times fired group) and significant (p < 0.001)
      increase in elongation value (28% for three times fired group) of Ni-Cr alloy.
      The microstructure of the control group specimen exhibited heterogeneous
      microstructure, and after each firing, microstructure of the alloy was gradually
      homogenized by formation of grain boundaries at the interdendritic interfaces. X
      ray diffraction pattern shows that the alloy exhibited four strong diffraction
      peaks within the range of 2theta = 40 degrees  to 100 degrees . After a third
      firing, intensity of these planes increased. CONCLUSIONS: Results of this study
      confirmed that nickel-based alloys become weaker after each firing process. After
      firing treatment, the microstructure of alloys showed decreased dendritic
      structure (i.e., homogenization, which was responsible for decrease in strength
      and an increase in ductility of the alloy); however, this decreased strength and
      hardness of Ni-Cr alloy after heat treatment was still superior to those of the
      most noble metal alloys used in dentistry. X-ray diffraction study showed that
      firing process led to relieving of stresses, which ultimately resulted in
      stability in the crystal structure of alloy.

PMID- 26215350
TI  - Formation and maintenance of the BBB.
AB  - The central nervous system (CNS) is vascularized by a dense capillary network
      that is critical to deliver oxygen and nutrients, and remove carbon dioxide and
      waste products, from the neural tissue. These blood vessels contain a series of
      properties, termed the blood-brain barrier (BBB), which distinguishes them from
      vasculature in other tissues, enabling CNS vessels to stringently regulate the
      transfer of ions, molecules and cells between the blood and the tissue. This
      barrier is critical to maintain brain homeostasis which allows for proper
      neuronal function and also to protect the tissue from injury and disease and many
      neurological diseases are associated with BBB dysfunction, including traumatic
      brain injuries, Alzheimer's disease, stroke, epilepsy, and multiple sclerosis.
      Therefore, a better understanding of the mechanisms controlling the development
      of the BBB may lead to improved comprehension of the pathophysiology of these
      diseases, and further aid in the identification of targets to modulate the
      barrier to treat different neurological diseases. Many of the properties of the
      BBB are possessed by the endothelial cells that form the walls of the blood
      vessels but are acquired through a series of complex cellular interactions with
      the microenvironment throughout its development. We will review what is known
      about the induction and regulation of BBB properties during development. 

PMID- 26215349
TI  - The boundary paradox in the Bithorax complex.
AB  - The parasegment-specific expression of the three Drosophila Bithorax complex
      homeotic genes is orchestrated by nine functionally autonomous regulatory
      domains. Functional autonomy depends upon special elements called boundaries or
      insulators that are located between each domain. The boundaries ensure the
      independent activity of each domain by blocking adventitious interactions with
      initiators, enhancers and silencers in the neighboring domains. However, this
      blocking activity poses a regulatory paradox--the Bithorax boundaries are also
      able to insulate promoters from regulatory interactions with enhancers and
      silencers and six of the nine Bithorax regulatory domains are separated from
      their target genes by at least one boundary element. Here we consider several
      mechanisms that have been suggested for how the Bithorax regulatory domains are
      able to bypass intervening boundary elements and direct the appropriate
      parasegment-specific temporal and spatial expression of their target gene.

PMID- 26215352
TI  - Specific Photochemical Dehydrocoupling of N-Heterocyclic Phosphanes and Their Use
      in the Photocatalytic Generation of Dihydrogen.
AB  - N-Heterocyclic phosphanes react under UV irradiation in a highly selective
      dehydrocoupling reaction to diphosphanes and H2. Computational studies suggest
      that the product formation is initiated by the formation of dimeric molecular
      associates whose electronic excitation yields H2 and a diphosphane. Combining the
      dehydrocoupling of sterically demanding phosphanes with Mg-reduction of the
      formed diphosphanes allows constructing a reaction cycle for the photocatalytic
      reductive generation of H2 from Et3NH(+).

PMID- 26215351
TI  - Signs and symptoms associated with primary tooth eruption: a clinical trial of
      nonpharmacological remedies.
AB  - BACKGROUND: To evaluate disturbances in primary tooth eruption and their
      management with nonpharmacological remedies. METHODS: In this nonrandomized
      clinical trial, 270 children aged between 8 and 36 months were selected and
      divided into 5 groups with 54 children initially enrolled in each group. The
      children were seen during an 8-day period during tooth eruption. At each
      appointment data were recorded from oral examination, tympanic temperature
      measurement and a questionnaire. The five methods used as remedies to reduce
      teething symptoms were: 1) cuddle therapy, 2) ice, 3) rubbing the gums, 4)
      teething rings and 5) food for chewing. Teething symptoms, the type of erupted
      tooth, symptoms of recovery and the mother's satisfaction with treatment were
      evaluated. RESULTS: Two hundred and fifty four children (mean age 16 +/- 7.2
      months) completed the study. The most frequent teething symptoms were drooling
      (92%), sleep disturbances (82.3%) and irritability (75.6%). These symptoms were
      more pronounced in low birth weight children (p > 0.05). Canine eruption led to
      more loss of appetite than incisor (p = 0.033) or molars eruption (p = 0.014).
      Low grade increases in body temperature were observed only on the day of eruption
      (36.70 +/- 0.39  degrees C), when body temperature was significantly different
      compared to the day before and the day after eruption (both p < 0.001). There was
      no significant correlation between fever as reported by mothers and temperature
      readings obtained by the investigators. The most favorable results for time to
      recovery and the mother's satisfaction were seen when teething rings were used,
      followed by cuddle therapy and rubbing the gums. CONCLUSIONS: There was no
      association between teething and symptoms such as fever or diarrhea. Low birth
      weight children may have more teething symptoms. Teething rings, cuddle therapy
      and rubbing the gums were the most effective methods to reduce symptoms. TRIAL
      REGISTRATION: Iranian Registry of Clinical Trials: code IRCT201211127402N3.

PMID- 26215353
TI  - Outcomes of surgery for young children with multivessel pulmonary vein stenosis.
AB  - OBJECTIVE: We pursued a multimodality approach to the treatment of patients with
      pulmonary vein stenosis, incorporating sutureless surgical repair, catheter
      interventions, and adjunctive chemotherapy. We report our outcomes after surgery.
      METHODS: Between January 2007 and August 2013, 49 patients with multivessel
      pulmonary vein stenosis underwent operations at our institution. We
      retrospectively reviewed data from a pulmonary vein stenosis registry and the
      medical records. RESULTS: At the time of the index operation, the median patient
      age was 6 months (range, 32 days-48 months) and weight was 4.9 kg (range, 2.1
      13.4 kg). Fourteen patients (28%) died during the follow-up period (median follow
      up was 0.5 years [range, 0.04-4.9 years]). There were 2 deaths (4%) within 30
      days. Age at repair <6 months, weight at repair <3 kg, and a preoperative right
      ventricular systolic pressure < 3/4 systemic were found to be associated with
      mortality. One patient required repeat operation for recurrent stenosis. Thirty
      nine patients (80%) underwent postoperative catheterizations. The median number
      of catheterizations per patient was 2 (range, 0-14). Twenty-nine patients (59%)
      underwent catheterizations with pulmonary vein intervention. The median number of
      catheterizations with intervention per patient was 1 (range, 0-14). There were no
      identifiable associations with need for or number of catheterizations with
      intervention. Ten patients were listed for lung transplantation: 4 patients were
      de-listed, 3 patients died waiting, and 3 patients underwent transplant.
      CONCLUSIONS: Using a multimodality approach, we observed acceptable early
      survival after operation in patients with pulmonary vein stenosis, despite the
      need for catheter reinterventions. Lung transplantation remains a viable option.

PMID- 26215354
TI  - Discussion.

PMID- 26215355
TI  - External stenting of vein grafts: Primum non nocere.

PMID- 26215356
TI  - Lung autotransplantation technique for postpneumonectomy-like syndrome.

PMID- 26215357
TI  - Discussion.

PMID- 26215358
TI  - Paravalvular regurgitation after conventional aortic and mitral valve
      replacement: A benchmark for alternative approaches.
AB  - OBJECTIVE: Paravalvular regurgitation is a known complication after transcatheter
      and sutureless aortic valve replacement. Paravalvular regurgitation also may
      develop in patients undergoing percutaneous mitral valve replacement. There are
      few studies on contemporary surgical valve replacement for comparison. We sought
      to determine the contemporary occurrence of paravalvular regurgitation after
      conventional surgical valve replacement. METHODS: We performed a single-center
      retrospective database review involving 1774 patients who underwent valve
      replacement surgery from April 2004 to December 2012: aortic in 1244, mitral in
      386, and combined aortic and mitral in 144. Follow-up echocardiography was
      performed in 73% of patients. Patients with endocarditis were analyzed separately
      from noninfectious paravalvular leaks. Statistical comparisons were performed to
      determine differences in paravalvular regurgitation incidence and survival.
      RESULTS: During follow-up, 1+ or greater (mild or more) paravalvular
      regurgitation occurred in 2.2% of aortic cases and 2.9% of mitral cases. There
      was 2+ or greater (moderate or more) paravalvular regurgitation in 0.9% of aortic
      and 2.2% of mitral cases (P = .10). After excluding endocarditis, late
      noninfectious regurgitation 2+ or greater was detected in 0.5% of aortic and 0.4%
      of mitral cases (P = .93); there were no reoperations or percutaneous closures
      for noninfectious paravalvular regurgitation. CONCLUSIONS: In an academic medical
      center, the overall rate of paravalvular regurgitation is low, and late
      clinically significant noninfectious paravalvular regurgitation is rare. The
      benchmark for paravalvular regurgitation after conventional valve replacement is
      high and should be considered when evaluating patients for transcatheter or
      sutureless valve replacement.

PMID- 26215359
TI  - Right anterior minithoracotomy for aortic valve replacement: 10-year experience
      of a single center.
AB  - OBJECTIVE: Minimally invasive aortic valve replacement (AVR) has been associated
      with several better outcomes over the standard full sternotomy approach. We
      revised our 10-year experience with right anterior minithoracotomy (RAMT) for
      AVR. METHODS: Between 2004 and 2014, a total of 593 patients (310 men; median
      age: 73.8 years) underwent AVR via RAMT. Preoperatively, a mixed valve lesion was
      diagnosed in 55 (9.3%) patients; and pure aortic regurgitation in 86 (14.5%).
      Mean logistic EuroSCORE I (European system for cardiac operative risk evaluation)
      was 7.4 (median: 5.76). RESULTS: In 302 (50.9%) patients, a sutureless or rapidly
      implantable biological prosthesis was used; in 23 (3.9%), a mechanical
      prosthesis; and in the remainder, a conventional biological prosthesis. A total
      of 113 (19.1%) patients had a small aortic annulus (<=21 mm). Operative times
      averaged 80 (median: 74) minutes of crossclamping time, and 117 (107) minutes of
      perfusion time; these were significantly shorter with a sutureless prostheses,
      compared with a sutured prostheses: perfusion 99 versus 134 minutes, P < .0005;
      aortic crossclamping time: 64 versus 97 minutes, P < .0005. The mean (median)
      assisted ventilation time was 9.8 (6) hours; intensive care unit stay was 1.5 (1)
      days; hospital length of stay was 6.6 (6) days. Overall in-hospital mortality was
      9 deaths (1.5%). At 31.5 months mean follow-up time (1531 cumulative patient
      years), 94.8% survival was observed. CONCLUSIONS: Minimally invasive AVR is a
      safe procedure, with low perioperative morbidity, and low rates of reoperation
      and death at late follow-up. Excellent outcomes can be achieved with minimally
      invasive AVR via right anterior minithoracotomy. Sutureless prostheses facilitate
      minimally invasive AVR and are associated with reduced operative times.

PMID- 26215360
TI  - The effect of surgeon volume on procedure selection in non-small cell lung cancer
      surgeries.
AB  - OBJECTIVES: Procedure selection by the surgeon can greatly affect patients'
      operative and long-term survival. This selection potentially reflects comfort
      with technically challenging surgeries. This study aims to examine surgeon
      choices for non-small cell lung cancer and whether surgeon volume predicts the
      type of procedure chosen, controlling for patient demographics, comorbidity, year
      of surgery, and institutional factors. METHODS: Data were abstracted from an
      Ontario population-based linked database from 2004 to 2011. Patient demographics,
      comorbidities, year of surgery, and institutional and surgical factors were
      evaluated. Three-level, random-effect, multilevel regression analyses were
      performed to examine factors influencing operative selection. RESULTS: Over the
      interval, 8070 patients (50.4% were male) underwent surgical resection, including
      pneumonectomy (n = 842), lobectomy (n = 6212), and wedge resection (n = 1002).
      Resections were performed by 124 unique physicians in 45 institutions. The
      proportion of patients undergoing pneumonectomy decreased from 14.8% in 2004 to
      7.6% in 2011. Multilevel regression analysis showed physician volume, age, year
      of procedure, gender, and comorbidities were predictive of performing a
      pneumonectomy. By adjusting for these variables, the results indicated that for
      each 10-unit increase in physician volume, the relative risk of performing a
      pneumonectomy decreased by 9.1% (95% confidence interval, 8.2-10.0, P = .04).
      CONCLUSIONS: Although patient and temporal factors influence the type of
      resection a patient receives for non-small cell lung cancer, surgeon volume also
      is a strong predictor. This study may be limited by minimal stage data, but the
      suggestion that a surgeon's total procedural volume for non-small cell lung
      cancer significantly influences procedure selection has implications on how we
      deliver care to this patient population.

PMID- 26215361
TI  - Impact of aortic annular geometry on aortic valve insufficiency: Insights from a
      preclinical, ex vivo, porcine model.
AB  - OBJECTIVES: We sought to create a model of aortic insufficiency in a left heart
      simulator combined with 3-dimensional echocardiography and finite element
      modeling of the aortic valve. We examined the effects of aortic root geometry
      alteration on aortic insufficiency. METHODS: Porcine aortic roots were analyzed
      on a left heart simulator before (control, n = 8) and after intervention (n = 8).
      Intervention entailed 3 vertical incisions at the sinotubular junction with
      diamond-shaped patches incorporated into the defects to increase the sinotubular
      junction diameter. Hemodynamic parameters were assessed, including regurgitant
      volume and fraction. Video and echocardiography images evaluated aortic valve
      function, coaptation surface area, aortic insufficiency, and effective
      regurgitant orifice area. Finite element modeling corroborated relationships
      between root geometry and aortic insufficiency, and examined cusp stress.
      RESULTS: The intervention resulted in a sinotubular junction diameter increase of
      55% +/- 4%. The sinotubular junction to ventriculo-aortic junction diameter ratio
      was significantly higher in the intervention group (1.89 +/- 0.16 vs 1.47 +/-
      0.04, P = .02). Increased sinotubular junction diameter resulted in aortic
      insufficiency assessed by regurgitant volume (28 +/- 7 mL vs 5 +/- 2 mL, P =
      .004), regurgitant fraction (36% +/- 5% vs 7% +/- 1%, P < .001), and effective
      regurgitant orifice (15 +/- 5 mm(2) vs 0 mm(2), P = .016). Intervention
      coaptation surface area was smaller (1.03 +/- 0.11 cm(2) vs 1.80 +/- 0.08 cm(2),
      P < .001). There was a linear correlation between increased sinotubular
      junction/ventriculo-aortic junction ratio and regurgitant fraction (R(2) = 0.65,
      P = .003). The finite element modeling demonstrated a similar relationship
      between increasing sinotubular junction diameter and aortic insufficiency
      severity, and between end-diastolic cusp stresses and sinotubular junction
      diameters (R(2) = 0.98, P < .001). CONCLUSIONS: In this model, increasing
      sinotubular junction diameter is linearly related to reduced coaptation surface
      area and increasing aortic insufficiency severity. This model provides new
      insights into aortic insufficiency mechanisms and may be used to evaluate novel
      interventions for aortic valve repair.

PMID- 26215362
TI  - Effects of bioDensity Training and Power Plate Whole-Body Vibration on Strength,
      Balance, and Functional Independence in Older Adults.
AB  - Reduced strength, balance, and functional independence diminish quality of life
      and increase health care costs. Sixty adults (82.2 +/- 4.9 years) were randomized
      to a control or three 12-week intervention groups: bioDensity (bD); Power Plate
      (PP) whole-body vibration (WBV); or bD+PP. bD involved one weekly 5-s maximal
      contraction of four muscle groups. PP involved two 5-min WBV sessions. Primary
      outcomes were strength, balance, and Functional Independence Measure (FIM). No
      groups differed initially. Strength significantly increased 22-51% for three
      muscle groups in bD and bD+PP (P < .001), with no changes in control and PP.
      Balance significantly improved in PP and bD+PP but not in control or bD. bD, PP,
      and bD+PP differentially improved FIM self-care and mobility. Strength
      improvements from weekly 5-min sessions of bD may impart health/clinical
      benefits. Balance and leg strength improvements suggest WBV beneficially impacts
      fall risk and incidence. Improved FIM scores are encouraging and justify larger
      controlled trials on bD and bD+PP efficacy. 

PMID- 26215363
TI  - Sternal gland structures in males of bean flower thrips, Megalurothrips
      sjostedti, and Poinsettia thrips, Echinothrips americanus, in comparison with
      those of western flower thrips, Frankliniella occidentalis (Thysanoptera:
      Thripidae).
AB  - Sternal pores are important features for identification of male thrips,
      especially within the subfamily Thripinae. They vary in shape, size and
      distribution even between species of one genus. Their functional role is
      speculated to be that of sex- and/or aggregation pheromone production. Yet,
      sexual aggregations are not reported in Echinothrips americanus, known to have
      sternal pores, while we observed aggregations in Megalurothrips sjostedti,
      previously reported to lack them. We examined the sternal glands and pores of the
      thripine species E. americanus and M. sjostedti males, in comparison with those
      of Frankliniella occidentalis using light microscopy, as well as scanning and
      transmission electron microscopy. Pore plates of F. occidentalis were ellipsoid
      and medial on sternites III-VII, while in E. americanus they were distributed as
      multiple micro pore plates on sternites III-VIII. In M. sjostedti they appeared
      as an extremely small pore in front of the posterior margin of each of sternites
      IV-VII. Pore plate and pore plate area were distributed similarly on sternites
      III-VII in F. occidentalis. However, in E. americanus the total pore plate area
      increased significantly from sternites III to VIII. Ultrastructure of cells
      associated with sternal glands showed typical characteristics of gland cells that
      differ in size, shape and number. The function of sternal glands is further
      discussed on the basis of morphological comparisons with other thrips species. 

PMID- 26215364
TI  - Transumbilical single incision laparoscopic sleeve gastrectomy (with video).

PMID- 26215365
TI  - [Embryonal paratesticular rhabdomyosarcoma: a case report and a literature
      review].
AB  - Paratesticular rhabdomyosarcoma is a rare tumor. Multimodality treatment should
      involve surgery, radiotherapy and chemotherapy, which are indicated according to
      risk groups. Risk group stratification depends on pretreatment staging and
      definitive histology. Patients older than 10years or those with suspected lymph
      nodes on imaging have higher incidence of lymph node involvement. Prognosis is
      excellent for localized tumors, survival rates exceed 90%. We report a case of
      embryonal paratesticular rhabdomyosarcoma treated in our institution. 

PMID- 26215366
TI  - [Long-term outcome of neoadjuvant radiochemotherapy followed by surgery for
      esophageal cancer: a single institution retrospective study of 102 patients].
AB  - PURPOSE AND OBJECTIVES: To report survival and morbidity of a large homogeneous
      cohort of patients with a locally advanced esophageal or cardia carcinoma and put
      in evidence predictive factors of locoregional control and survival. PATIENTS AND
      METHODS: Hundred and two patients were treated at the university hospital of
      Tours between 1990 and 2010 and received neo-adjuvant chemoradiation therapy with
      external irradiation (40Gy-44Gy) and two courses of chemotherapy (5-fluoro
      uracile and cisplatine). Esophagectomy associated with lymph node dissection was
      performed about ten weeks after the end of chemoradiation therapy. RESULTS: The
      median follow-up was 22.4 months [6-185 months]. The overall survival rates at 2
      and 5years were 53% and 27%, respectively. The median overall survival was
      estimated at 27months. The overall 2-year survival between patients "responders"
      and patients "non-responders" was 67% vs 26%, respectively (P<0.0001). In case of
      histological response, there was a benefit in terms of overall survival
      (P<0.0001), locoregional control (P<0.0036) and disease-free survival (P<0.001).
      Overall survival at 2years was 64% for ypN0 group vs 32% for ypN1 group
      (P<0.0001). The median survival was estimated at 37months against 15months in the
      absence of lymph node involvement (P<0.0001). CONCLUSION: Our results in terms of
      survival, tolerance and morbidity and mortality were comparable to those in the
      literature. Complete histological response of lymph node was associated with an
      improvement of local control, disease-free survival and overall survival.

PMID- 26215367
TI  - [Primary neuroendocrine tumors of the breast: a retrospective study of 21 cases
      and literature review].
AB  - PURPOSE: The aim of the present study was to discuss the epidemiology, clinical
      and pathologic features, treatment, and prognosis of primary neuroendocrine
      carcinomas of the breast. PATIENTS AND METHODS: We report 21 cases diagnosed over
      a period of 12 years (1995-2011) at the university hospital of Sfax. A review of
      the clinical data with pathology and immunohistochemistry study was carried out
      for all the cases. RESULTS: The average age was 62 years (34-86 years). At the
      time of the diagnosis, tumours were classified T1 and T2 (16 cases), N1 (11
      cases) and M1 in two cases. The histological examination has shown 13 cases of
      solid neuroendocrine carcinoma, six cases of large cell type and two cases of
      atypical carcinoid. Grade I and II SBR were found in 18 cases. Eighty-one percent
      of the tumours were reactive for synaptophysin; all tumours were positive for
      chromogranin. Thirteen (61.9%) tumours were estrogen receptor-positive and 12
      (57.5%) progesterone receptor-positive. Nineteen (90.5%) tumours were negative
      for HER2/neu. Overall five-year survival was 72.7%. All patients had surgical
      treatment with modified radical mastectomy in 13 cases. Adjuvant treatment was
      indicated according to histopronostic elements. CONCLUSION: For primary
      neuroendocrine carcinoma of the breast, multivariate analysis identified three
      predictive factors for mortality: disease stage, histological grade and lymph
      node involvement.

PMID- 26215368
TI  - Representing virus-host interactions and other multi-organism processes in the
      Gene Ontology.
AB  - BACKGROUND: The Gene Ontology project is a collaborative effort to provide
      descriptions of gene products in a consistent and computable language, and in a
      species-independent manner. The Gene Ontology is designed to be applicable to all
      organisms but up to now has been largely under-utilized for prokaryotes and
      viruses, in part because of a lack of appropriate ontology terms. METHODS: To
      address this issue, we have developed a set of Gene Ontology classes that are
      applicable to microbes and their hosts, improving both coverage and quality in
      this area of the Gene Ontology. Describing microbial and viral gene products
      brings with it the additional challenge of capturing both the host and the
      microbe. Recognising this, we have worked closely with annotation groups to test
      and optimize the GO classes, and we describe here a set of annotation guidelines
      that allow the controlled description of two interacting organisms. CONCLUSIONS:
      Building on the microbial resources already in existence such as ViralZone,
      UniProtKB keywords and MeGO, this project provides an integrated ontology to
      describe interactions between microbial species and their hosts, with mappings to
      the external resources above. Housing this information within the freely
      accessible Gene Ontology project allows the classes and annotation structure to
      be utilized by a large community of biologists and users.

PMID- 26215369
TI  - Factors associated with non-vaccination against measles in northeastern Brazil:
      Clues about causes of the 2015 outbreak.
AB  - Measles is a highly contagious disease that can be effectively prevented through
      vaccination. The recent increase in vaccination coverage was successful in
      reducing the mortality globally of the disease by 74%. As a whole, the Americas
      have been considered a disease-free zone. However, it is known that if an
      immunization programs fails, there will be an accumulation of susceptible people
      that can lead to disease outbreaks. Recently, both the United States and Brazil
      faced outbreaks of measles. The present study aims to identify the determining
      factors of non-vaccination in Brazil in two different vaccination coverage
      moments, to provide clues as to the causes of current outbreaks. Data were drawn
      from five population-based cross-sectional studies that surveyed a representative
      sample of preschool children from 1987 to 2007 (9585 children in total). To
      assess children's vaccination status, two different information sources were
      used: information provided by mothers and information from children's health
      cards. Multivariate analyses with logistic binary regression models were
      conducted. After adjustment for confounding factors, it was observed that in
      1987, with 48.2% vaccination coverage, socioeconomic, maternal, nutritional
      factors and access to health facilities were important, while in 2007 (96.7%
      coverage), nutritional and maternal factors were important. Distinct patterns of
      determinants of non-vaccination were also found. In addition, the low coverage in
      1987 resulted in a current pool of adults who were not immunized as children;
      this may have contributed to the beginning of the current Brazilian outbreak.
      Globally, there are two standards of vaccination coverage (low and high).
      Therefore, discussion of the determinants of non-vaccination is important. Our
      findings suggest vulnerable groups should receive special attention to ensure
      they are protected. It is also important to consider the possible impact of pools
      of adults not immunized. 

PMID- 26215370
TI  - Measles seroprevalence in Chiradzulu district, Malawi: Implications for
      evaluating vaccine coverage.
AB  - INTRODUCTION: Self-reported measles vaccination coverage is frequently used to
      inform vaccination strategies in resource-poor settings. However, little is known
      to what extent this is a reliable indicator of underlying seroprotection,
      information that could provide guidance ensuring the success of measles control
      and elimination strategies. METHODS: As part of a study exploring HIV infection
      and measles susceptibility, we conveniently sampled consenting HIV-uninfected
      patients presenting at the HIV voluntary counselling and testing centre, and HIV
      infected patients presenting for regular care, in Chiradzulu district hospital,
      Malawi, between January and September 2012. RESULTS: A total of 2106 participants
      were recruited between January and September 2012, three quarters of whom were
      HIV positive. Vaccination cards were available for just 7 participants (0.36%).
      91.9% of participants were measles seropositive. Older age (OR=1.11 per year
      increase in age; 95%CI: 1.09-1.14) and being female (OR=1.90; 95%CI: 1.26-2.87)
      were both associated with significantly increased odds for seroprotection. Prior
      vaccination history was associated with lower odds (Odds Ratio (OR)=0.44; 95%
      confidence interval (CI): 0.22-0.85) for confirmed seropositivity. Previous
      measles infection was not significantly associated with seroprotection (OR=1.31;
      95%CI: 0.49-3.51). Protection by history and serological status were concordant
      for 64.3% of participants <35 years old. However, analysis by age group reveals
      important differences in concordance between the ages, with a greater degree of
      discordance among younger ages. Vaccination and/or infection history as a
      predictor of seropositivity was 75.8% sensitive, but just 10.3% specific.
      CONCLUSION: Reported vaccination and previous infection were poor predictors of
      seropositivity, suggesting these may be unreliable indicators of seroprotection
      status. Such serosurveys may be indicated in similar settings in which
      overestimation of the proportion of seroprotected individuals could have
      important ramifications if used to guide vaccination strategies.

PMID- 26215371
TI  - Expert Involvement and Adherence to Medical Evidence in Medical Mobile Phone
      Apps: A Systematic Review.
AB  - BACKGROUND: Both clinicians and patients use medical mobile phone apps. Anyone
      can publish medical apps, which leads to contents with variable quality that may
      have a serious impact on human lives. We herein provide an overview of the
      prevalence of expert involvement in app development and whether or not app
      contents adhere to current medical evidence. OBJECTIVE: To systematically review
      studies evaluating expert involvement or adherence of app content to medical
      evidence in medical mobile phone apps. METHODS: We systematically searched 3
      databases (PubMed, The Cochrane Library, and EMBASE), and included studies
      evaluating expert involvement or adherence of app content to medical evidence in
      medical mobile phone apps. Two authors performed data extraction independently.
      Qualitative analysis of the included studies was performed. RESULTS: Based on
      inclusion criteria, 52 studies were included in this review. These studies
      assessed a total of 6520 apps. Studies dealt with a variety of medical
      specialties and topics. As much as 28 studies assessed expert involvement, which
      was found in 9-67% of the assessed apps. Thirty studies (including 6 studies that
      also assessed expert involvement) assessed adherence of app content to current
      medical evidence. Thirteen studies found that 10-87% of the assessed apps adhered
      fully to the compared evidence (published studies, recommendations, and
      guidelines). Seventeen studies found that none of the assessed apps (n=2237)
      adhered fully to the compared evidence. CONCLUSIONS: Most medical mobile phone
      apps lack expert involvement and do not adhere to relevant medical evidence.

PMID- 26215372
TI  - Establishment of a heterotypic 3D culture system to evaluate the interaction of
      TREG lymphocytes and NK cells with breast cancer.
AB  - Three-dimensional (3D) culture approaches to investigate breast tumour
      progression are yielding information more reminiscent of the in vivo
      microenvironment. We have established a 3D Matrigel system to determine the
      interactions of luminal phenotype MCF-7 cells and basal phenotype MDA-MB-231
      cells with regulatory T lymphocytes and Natural Killer cells. Immune cells were
      isolated from peripheral blood using magnetic cell sorting and their phenotype
      validated using flow cytometry both before and after activation with IL-2 and
      phytohaemagglutinin. Following the establishment of the heterotypic culture
      system, tumour cells displayed morphologies and cell-cell associations distinct
      to that observed in 2D monolayer cultures, and associated with tissue remodelling
      and invasion processes. We found that the level of CCL4 secretion was influenced
      by breast cancer phenotype and immune stimulation. We further established that
      for RNA extraction, the use of proteinase K in conjunction with the Qiagen RNeasy
      Mini Kit and only off-column DNA digestion gave the best RNA yield, purity and
      integrity. We also investigated the efficacy of the culture system for
      immunolocalisation of the biomarkers oestrogen receptor-alpha and the
      glycoprotein mucin 1 in luminal phenotype breast cancer cells; and epidermal
      growth factor receptor in basal phenotype breast cancer cells, in formalin-fixed,
      paraffin-wax embedded cultures. The expression of these markers was shown to vary
      under immune mediation. We thus demonstrate the feasibility of using this co
      culture system for downstream applications including cytokine analysis,
      immunolocalisation of tumour biomarkers on serial sections and RNA extraction in
      accordance with MIQE guidelines. 

PMID- 26215373
TI  - Optical Activity in the Near-IR Region: The lambda=980 nm Multiplet of Chiral
      Yb3+ Complexes.
AB  - We used a very simplified electrostatic model based on charge and polarizability
      of atoms and groups on an organic ligand around a lanthanide ion to predict the
      near-infrared electronic circular dichroism (NIR ECD) spectra of Yb3+ (a
      monoelectronic ion). We tuned our method by using two widely different complexes.
      The first was the heterobimetallic species CsYb(hfbc)4 [hfbc=(-)-3
      heptafluorobutyrylcamphorate], in which the ligand is a diketonate and, as such,
      is endowed with a chromophore with strong UV absorption (pi-pi* ). Its oxygen
      atoms define a square antiprism, which provides a symmetric coordination
      polyhedron. The second system was Yb DOTMA [DOTMA=(1R,4R,7R,10R)
      alpha,alpha',alpha'',alpha'''-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid], a chiral Yb analogue of Gd DOTA (DOTA=1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid), in which the ligand lacks
      relevant electronic transitions and provides a dissymmetric cage. The relative
      weights of dynamic (ligand polarization) and static contributions to Yb NIR ECD
      were evaluated, and the spectra appear to have been well predicted by theory
      through the introduction of a heuristic weight factor. To validate the approach
      and to confirm the value of the weight factor, we applied it to two other
      compounds, namely, Na3 Yb(BINOLate)3 and Yb(BINOLAM)3 [BINOLate=2,2'-dihydroxy
      1,1'-binaphthyl; BINOLAM=3,3'-bis(diethylaminomethyl)-1-1'-bi-2-naphthol].

PMID- 26215374
TI  - Bone marrow-derived macrophages exclusively expressed caveolin-2: The role of
      inflammatory activators and hypoxia.
AB  - Caveolins are specific proteins involved in regulation of signal transduction to
      intracellular space. Still, their contribution to immune functions has not been
      completely clarified. Thus, we decided to characterize the expression of
      caveolins in bone marrow-derived macrophages (BMDMs) under resting and
      inflammatory conditions. The effect of classical activators (lipopolysaccharide,
      LPS; interferon-gamma, IFN-gamma) was further potentiated with hypoxic (5% O2)
      conditions. The activation of p44/42-extracellular signal-regulated kinases 1 and
      2 (ERK1/2) and expression of caveolin-1, -2, and -3, hypoxia inducible factor-1
      alpha (HIF-1alpha), as well as inducible nitric oxide synthase (iNOS) was
      monitored using the Western blot technique. The production of nitric oxide (NO)
      and tumor necrosis factor-alpha (TNFalpha) was analyzed by Griess method or
      ELISA, respectively. BMDMs were also transfected with siRNA against caveolin-2.
      Importantly, our study showed for the first time that BMDMs expressed only
      caveolin-2, and its level decreased after activation of macrophages with LPS, IFN
      gamma, and/or hypoxia. The expression of caveolin-2 negatively correlates with
      the iNOS and HIF-1alpha protein levels, as well as with the LPS/IFN-gamma- and
      hypoxia-induced activation of ERK1/2. We concluded that caveolin-2 is most
      probably involved in regulation of pro-inflammatory responses of BMDMs, triggered
      via activation of ERK1/2. 

PMID- 26215375
TI  - A label-free cyclic assembly of G-quadruplex nanowires for cascade amplification
      detection of T4 polynucleotide kinase activity and inhibition.
AB  - Several fluorescence methods have been developed for sensitive detection of PNK
      activity based on signal amplification techniques, but they need fluorescently
      labeled DNA probes and superabundant assistant enzymes. We have addressed these
      limitations and report here a label-free and enzyme-free amplification strategy
      for sensitively and specifically studying PNK activity and inhibition via
      hybridization chain reaction (HCR). First, the phosphorylation of hairpin DNA H1
      by T4 PNK makes it be specifically digested by lambda exonuclease (lambda exo)
      from 5' to 3' direction to generate a single-stranded initiator which can
      successively open hairpins H2 and H3 to trigger an autonomous assembly of long
      DNA nanowires. Meanwhile, an intermolecular G-quadruplex is formed between H2 and
      H3, thereby providing fluorescence enhancement of N-methyl mesoporphyrin IX (NMM)
      which is a highly quadruplex-selective fluorophore. So, the PNK activity can be
      facilely and sensitively detected by using NMM as a signal probe which provides a
      low background signal to improve the overall sensitivity, resulting in the
      detection limit of 3.37 * 10(-4) U mL(-1). More importantly, its successful
      application for detecting PNK activity in a complex biological matrix and
      studying the inhibition effects of PNK inhibitors demonstrated that it provides a
      promising platform for screening PNK inhibitors as well as detecting PNK
      activity. Therefore, it is a highly sensitive, specific, reliable and cost
      effective strategy which shows great potential for biological process research,
      drug discovery, and clinical diagnostics. 

PMID- 26215376
TI  - Functional characterization of PeIF5B as eIF5B homologue from Pisum sativum.
AB  - We earlier reported 'PeIF5B' as a novel factor from Pisum sativum that has
      sequence similarity to eIF5B (S. Rasheedi, S. Ghosh, M. Suragani et al., P.
      sativum contains a factor with strong homology to eIF5B, Gene 399 (2007) 144
      151). The main aim of the present study was to perform functional
      characterization of PeIF5B as an eIF5B homologue from plant system. PeIF5B shows
      binding to Met - tRNA(f)(Met), hydrolyses GTP and interacts with ribosomes. In
      vivo growth complementation analysis shows that PeIF5B partially complements its
      yeast homologue. Interestingly, PeIF5B mainly localizes in the nucleus as
      confirmed by nuclear localization signal (NLS) prediction, confocal imaging and
      immunoblots of cellular fractions. Similar to the yeast eIF5B but unlike the
      human orthologue, PeIF5B is an intron-less gene. This study highlights PeIF5B's
      role as a functional eIF5B homologue possibly participating in nuclear
      translation in plant system.

PMID- 26215377
TI  - DNA replication restart and cellular dynamics of Hef helicase/nuclease protein in
      Haloferax volcanii.
AB  - Understanding how frequently spontaneous replication arrests occur and how
      archaea deal with these arrests are very interesting and challenging research
      topics. Here we will described how genetic and imaging studies have revealed the
      central role of the archaeal helicase/nuclease Hef belonging to the
      XPF/MUS81/FANCM family of endonucleases in repair of arrested replication forks.
      Special focus will be on description of a recently developed combination of
      genetic and imaging tools to study the dynamic localization of a functional
      Hef::GFP (Green Fluorescent Protein) fusion protein in the living cells of
      halophilic archaea Haloferax volcanii. As Archaea provide an excellent and unique
      model for understanding how DNA replication is regulated to allow replication of
      a circular DNA molecule either from single or multiple replication origins, we
      will also summarize recent studies that have revealed peculiar features regarding
      DNA replication, particularly in halophilic archaea. We strongly believe that
      fundamental knowledge of our on-going studies will shed light on the evolutionary
      history of the DNA replication machinery and will help to establish general rules
      concerning replication restart and the key role of recombination proteins not
      only in bacteria, yeast and higher eukaryotes but also in archaea. 

PMID- 26215378
TI  - The Role of Immigrant Concentration Within and Beyond Residential Neighborhoods
      in Adolescent Alcohol Use.
AB  - Neighborhoods are salient contexts for youth that shape adolescent development
      partly through informal social controls on their behavior. This research examines
      how immigrant concentration within and beyond the residential neighborhood
      influences adolescent alcohol use. Residential neighborhood immigrant
      concentration may lead to a cohesive, enclave-like community that protects
      against adolescent alcohol use. But heterogeneity in the immigrant concentrations
      characterizing the places residents visit as they engage in routine activities
      outside of the neighborhood where they live may weaken the social control
      benefits of the social ties and shared cultural orientations present in enclave
      communities. This study investigates whether the protective influence of
      residential neighborhood immigrant concentration on adolescent alcohol
      consumption diminishes when youth live in communities where residents
      collectively are exposed to areas with more diverse immigrant concentrations.
      This study tests this contention by analyzing survey and geographic routine
      activity space data from the Los Angeles Family and Neighborhood Survey, and the
      2000 census. The sample includes 793 adolescents (48.7% female, 16.5% foreign
      born Latino, 42.5% US-born Latino, 11.0% black, 30% white/other) between the ages
      of 12 and 17 who live in 65 neighborhoods in Los Angeles County. Immigrant
      concentration among these neighborhoods derives primarily from Latin America. The
      results from multilevel models show that immigrant concentration protects against
      adolescent alcohol use only when there is low neighborhood-level diversity of
      exposures to immigrant concentration among the contexts residents visit outside
      of their residential neighborhood. This research highlights the importance of
      considering the effects of aggregate exposures to non-home contexts on adolescent
      wellbeing.

PMID- 26215379
TI  - Parental Involvement Across Middle and High School: Exploring Contributions of
      Individual and Neighborhood Characteristics.
AB  - Parental involvement in education is crucial during adolescence when grades
      decline and youth autonomy increases. This study examined parental involvement
      trajectories from 7th to 11th grade and explored whether individual and
      neighborhood characteristics affected this change. European American and African
      American (66 %) families participated (N = 1377, primary caregivers: 92 % female;
      adolescents: 51 % male, initial age range: 11-14). Results showed that, over
      time, parents reduced home- and school-based involvement but consistently engaged
      in academic socialization. Individual and neighborhood characteristics
      contributed differentially to parental involvement trajectories. These findings
      suggest that parental investment in adolescents' education persists during this
      critical developmental period, but individual and contextual differences impact
      the use of these strategies, which has implications for family-school
      partnerships and interventions. 

PMID- 26215381
TI  - Placental plasticity in monochorionic twins: Impact on birth weight and placental
      weight.
AB  - INTRODUCTION: The knowledge about adaptive mechanisms of monochorionic placentas
      to fulfill the demands of two instead of one fetus is largely speculative. The
      aim of our study was to investigate the impact of chorionicity on birth weight
      and placental weight in twin pregnancies. METHODS: Forty Monochorionic (MC) and
      43 dichorionic (DC) twin pregnancies were included in this retrospective study.
      Individual and total (sum of both twins) birth weights, placental weights ratios
      between placental and birth weights and observed-to-expected (O/E)-ratios were
      calculated and analyzed. Additionally, we investigated whether in twin
      pregnancies placental and birth weights follow the law of allometric metabolic
      scaling. RESULTS: MC pregnancies showed higher placental O/E-ratios than DC ones
      (2.25 +/- 0.85 versus 1.66 +/- 0.61; p < 0.05), whereas the total neonatal birth
      weight O/E-ratios were not different. In DC twins total placental weights
      correlated significantly with gestational age (r = 0.74, p < 0.001), but not in
      MC twins. Analysis of deliveries <=32 weeks revealed that the placenta to birth
      weight ratio in MC twins was higher than in matched DC twins (0.49 +/- 0.3 versus
      0.24 +/- 0.03; p = 0.03). Allometric metabolic scaling revealed that dichorionic
      twin placentas scale with birth weight, while the monochorionic ones do not.
      DISCUSSION: The weight of MC placentas compared to that of DC is not gestational
      age dependent in the third trimester. Therefore an early accelerated placental
      growth pattern has to be postulated which leads to an excess placental mass
      particularly below 32 weeks of gestation. The monochorionic twins do not follow
      allometric metabolic scaling principle making them more vulnerable to placental
      compromise.

PMID- 26215380
TI  - The iBeetle large-scale RNAi screen reveals gene functions for insect development
      and physiology.
AB  - Genetic screens are powerful tools to identify the genes required for a given
      biological process. However, for technical reasons, comprehensive screens have
      been restricted to very few model organisms. Therefore, although deep sequencing
      is revealing the genes of ever more insect species, the functional studies
      predominantly focus on candidate genes previously identified in Drosophila, which
      is biasing research towards conserved gene functions. RNAi screens in other
      organisms promise to reduce this bias. Here we present the results of the iBeetle
      screen, a large-scale, unbiased RNAi screen in the red flour beetle, Tribolium
      castaneum, which identifies gene functions in embryonic and postembryonic
      development, physiology and cell biology. The utility of Tribolium as a screening
      platform is demonstrated by the identification of genes involved in insect
      epithelial adhesion. This work transcends the restrictions of the candidate gene
      approach and opens fields of research not accessible in Drosophila. 

PMID- 26215382
TI  - Initial clinical experience with BRAF(V600E) mutation analysis of core-needle
      biopsy specimens from thyroid nodules.
AB  - OBJECTIVE: The accurate diagnosis of thyroid nodules is important for making
      management decisions. The purpose of this study was to evaluate the feasibility
      of core-needle biopsy with BRAF(V600E) mutation analysis (CNB + BRAF(V600E) ) and
      to compare the clinical usefulness of CNB + BRAF(V600E) and fine-needle
      aspiration with BRAF(V600E) mutation analysis (FNA + BRAF(V600E) ) in the
      diagnosis of thyroid malignancy. DESIGN, PATIENTS AND MEASUREMENTS: The results
      of BRAF(V600E) mutation analyses of 820 nodules from 820 patients (153 men, 667
      women; mean age, 51.1 years), who underwent CNB + BRAF(V600E) (n = 256) or FNA +
      BRAF(V600E) (n = 564) between January 2011 and March 2012 were retrospectively
      evaluated. The feasibility of CNB + BRAF(V600E) was assessed by comparing its
      rate of detection of BRAF(V600E) mutations and positive predictive value with
      those of FNA + BRAF(V600E) . The clinical usefulness of CNB + BRAF(V600E) was
      determined by comparing rates of inconclusive results, the additional value of
      BRAF(V600E) mutation analysis, diagnostic surgery and diagnostic performance with
      those of FNA + BRAF(V600E) . RESULTS: CNB + BRAF(V600E) and FNA + BRAF(V600E) had
      similar rates of BRAF(V600E) mutation detection (66.3% vs 64.4%, P = 0.883) and
      positive predictive value (100.0% vs 96.6%, P = 0.135). CNB + BRAF(V600E) had a
      significantly higher diagnostic accuracy rate (95.7% vs 85.9%, P < 0.001), and
      significantly lower rates of inconclusive results (8.2% vs 51.8%, P < 0.001), and
      diagnostic surgery (8.9% vs 22.3%, P = 0.006), than FNA + BRAF(V600E) .
      CONCLUSIONS: The greater diagnostic performance of CNB + BRAF(V600E) and its
      lower rate of inconclusive results than FNA + BRAF(V600E) suggest that CNB +
      BRAF(V600E) can reduce rates of preventable diagnostic surgery.

PMID- 26215383
TI  - Detection of the posterior superior alveolar artery in the lateral sinus wall
      using computed tomography/cone beam computed tomography: a prevalence meta
      analysis study and systematic review.
AB  - A systematic search of MEDLINE, Embase, and Proceedings Web of Science was
      undertaken to assess the prevalence of the posterior superior alveolar artery
      (PSAA) in the lateral sinus wall in sinus lift patients, as identified using
      computed tomography (CT)/cone beam computed tomography (CBCT). For inclusion, the
      article had to report PSAA detection in the bony wall using CT and/or CBCT in
      patients with subsinus edentulism. Studies on post-mortem findings, mixed samples
      (living and cadaveric), those presenting pooled results only, or studies
      performed for a sinus pathology were excluded. Heterogeneity was checked using an
      adapted version of the DerSimonian and Laird Q test, and quantified by
      calculating the proportion of the total variance due to between-study variance
      (Ri statistic). Eight hundred and eleven single papers were reviewed and filtered
      according to the inclusion/exclusion criteria. Ten studies were selected (1647
      patients and 2740 maxillary sinuses (study unit)). The pooled prevalence of PSAA
      was 62.02 (95% confidence interval (CI) 46.33-77.71). CBCT studies detected PSAA
      more frequently (78.12, 95% CI 61.25-94.98) than CT studies (51.19, 95% CI 42.33
      60.05). Conventional CT revealed thicker arteries than CBCT. It is concluded that
      PSAA detection is more frequent when CBCT explorations are used. Additional
      comparative studies controlling for potential confounding factors are needed to
      ascertain the actual diagnostic value of radiographic explorations for assessing
      the PSAA prior to sinus floor elevation procedures. 

PMID- 26215384
TI  - Lighting, sleep and circadian rhythm: An intervention study in the intensive care
      unit.
AB  - Patients in an intensive care unit (ICU) may risk disruption of their circadian
      rhythm. In an intervention research project a cycled lighting system was set up
      in an ICU room to support patients' circadian rhythm. Part I aimed to compare
      experiences of the lighting environment in two rooms with different lighting
      environments by lighting experiences questionnaire. The results indicated
      differences in advantage for the patients in the intervention room (n=48), in
      perception of daytime brightness (p=0.004). In nighttime, greater lighting
      variation (p=0.005) was found in the ordinary room (n=52). Part II aimed to
      describe experiences of lighting in the room equipped with the cycled lighting
      environment. Patients (n=19) were interviewed and the results were presented in
      categories: "A dynamic lighting environment", "Impact of lighting on patients'
      sleep", "The impact of lighting/lights on circadian rhythm" and "The lighting
      calms". Most had experiences from sleep disorders and half had nightmares/sights
      and circadian rhythm disruption. Nearly all were pleased with the cycled lighting
      environment, which together with daylight supported their circadian rhythm. In
      night's actual lighting levels helped patients and staff to connect which
      engendered feelings of calm. 

PMID- 26215385
TI  - Summaries for Patients. Variation in Blood Pressure Readings and the Risk for
      Cardiovascular Disease.

PMID- 26215386
TI  - Gut microbiota: Microbiota and neuroimmune signalling-Metchnikoff to microglia.

PMID- 26215387
TI  - Biliary tract: Solving the conundrum of cholangiocyte differentiation.

PMID- 26215388
TI  - Surgery: Bile diversion comparable to bariatric surgery in mice.

PMID- 26215389
TI  - Barriers and alternatives to pediatric rheumatology referrals: survey of general
      pediatricians in the United States.
AB  - BACKGROUND: Access to pediatric rheumatology (PR) care is limited, however the
      impact that limited access to PR has on pediatricians has not been examined. The
      goal of this study was to investigate barriers to PR referrals and resulting
      alternative referral patterns among primary pediatricians. METHODS: A web-based
      survey was emailed to primary pediatricians practicing in Minnesota, North
      Dakota, and South Dakota in order to investigate access to PR care issues. Basic
      descriptive analysis was performed. RESULTS: The response rate was 15 % (93/609).
      Twenty-nine percent (27/92) of respondents' clinics were at least two hours by
      car from a pediatric rheumatologist, and 9 % (8/92) were more than six hours
      away. Ninety-two percent (85/92) had referred a patient to PR at least once, but
      89 % (83/93) had experienced a situation in which they considered a referral to
      PR but ultimately did not. Many had referred to other subspecialists instead: 29
      % (24/83) to pediatric infectious disease, 20 % to adult rheumatology, and 12 %
      to pediatric orthopedics, while 34 % managed the patient themselves. Thirty-five
      percent (32/60) had referred to an adult rheumatologist, commonly due to
      decreased travel (44 %), while physician preference was never selected as a
      reason. CONCLUSION: Pediatricians often refer children with possible rheumatic
      disease to specialists other than PR mainly due to long travel distances.
      Referral to adult rheumatologists occurs, but not based on pediatrician
      preference. These findings suggest that the PR workforce is inadequate to meet
      demand, at least in the Upper Midwest. Interventions are needed to improve access
      to PR care.

PMID- 26215390
TI  - Fulminant hepatitis B reactivation leading to liver transplantation in a patient
      with chronic hepatitis C treated with simeprevir and sofosbuvir: a case report.
AB  - INTRODUCTION: Hepatitis B and C coinfection is commonly seen in clinical
      practice. In coinfected individuals, high levels of hepatitis C viremia are often
      associated with low levels of serum hepatitis B DNA. Hepatitis B reactivation in
      hepatitis C-infected patients treated with pegylated interferon and ribavirin has
      been reported, but severe or fulminant reactivation is uncommon. Hepatitis C
      treatment-associated hepatitis B reactivation in patients with chronic hepatitis
      C and isolated core antibody has not been reported previously. CASE PRESENTATION:
      A 59-year-old white woman with chronic hepatitis C genotype 1B and isolated
      hepatitis B core antibody initiated treatment with simeprevir, sofosbuvir, and
      ribavirin for treatment of chronic hepatitis C. She responded very well to
      treatment initially with near normalization of aminotransferases and hepatitis C
      viral load suppressed to below the level of quantification after 4 weeks of
      treatment. At week 11 of a planned 12-week course, she developed fulminant
      hepatic failure due to hepatitis B reactivation and ultimately required liver
      transplantation. Fortunately, her posttransplant clinical course was
      unremarkable. CONCLUSIONS: This is the first report of hepatitis B reactivation
      in a patient with isolated hepatitis B core antibody leading to fulminant hepatic
      failure and liver transplantation after initiation of treatment with sofosbuvir,
      simeprevir, and ribavirin for hepatitis C. This case raises the concern for the
      risk of severe hepatitis B reactivation in hepatitis B and C-coinfected patients
      or chronic hepatitis C-infected patients with isolated hepatitis B core antibody
      treated with direct-acting antiviral drugs for hepatitis C.

PMID- 26215391
TI  - Polio-Like Illness Associated With Outbreak of Upper Respiratory Tract Infection
      in Children.
AB  - Poliomyelitis is a historically devastating neurological complication of
      poliovirus infection. Poliovirus vaccines have decreased the incidence of
      poliomyelitis to 209 global cases in 2014, with new cases of acute flaccid
      myelitis primarily associated with nonpolio enteroviruses. Recently, during
      outbreaks of enterovirus D68 throughout North America and Europe, cases of acute
      flaccid myelitis have been reported, suggesting another nonpolio enterovirus
      associated with acute flaccid myelitis. The authors describe 3 patients diagnosed
      with acute flaccid myelitis during a province-wide outbreak of enterovirus D68
      with the virus detected in 2 of the patients. Given the significant morbidity
      associated with acute flaccid myelitis and potential for nonpolio enterovirus to
      cause outbreaks, prompt identification and notification of public health
      authorities are warranted. 

PMID- 26215392
TI  - Seizure Recurrence in Developmentally and Neurologically Normal Children With a
      Newly Diagnosed Unprovoked Seizure.
AB  - This study aims to assess recurrence risk in developmentally and neurologically
      normal children with a newly diagnosed unprovoked seizure. The medical record was
      retrospectively reviewed in 393 children who had a newly diagnosed, unprovoked
      seizure. A total of 152 children met inclusion criteria. The relationship between
      seizure recurrence and variables was examined. Seventy cases had recurrent
      seizures. Total 113 cases had follow-up data and 70 cases of these (63.7%)
      experienced recurrent seizures. EEG was abnormal in 65 (44.8%): focal
      epileptiform abnormality in 34 cases (23.4%) and generalized epileptiform
      abnormality in 23 cases (15.9%). Brain MRI revealed any structural abnormality in
      14 of 86 cases (16.3%). Neither EEG abnormality nor brain MRI abnormality was
      statistically significantly associated with increased seizure recurrence in this
      cohort. Further study is required to confirm the EEG and brain MRI findings in
      otherwise normal children with a newly diagnosed unprovoked seizure. 

PMID- 26215393
TI  - Young men being treated for cancer are more likely than women to make fertility
      preservation arrangements, US study shows.

PMID- 26215394
TI  - Attenuated Semliki Forest virus for cancer treatment in dogs: safety assessment
      in two laboratory Beagles.
AB  - BACKGROUND: Dogs suffer from spontaneous tumors which may be amenable to
      therapies developed for human cancer patients, and dogs may serve as large-animal
      cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously
      showed promise in targeting human tumor xenografts in mice, but the oncolytic
      capacity of the virus in canine cancer cells and the safety of the virus in
      higher mammals such as dogs, are not known. We therefore assessed the oncolytic
      potency of VA7-EGFP against canine cancer cells by infectivity and viability
      assays in two dog solid tumor cell lines. Furthermore we performed a 3-week
      safety study in two adult Beagles which received a single intravenous injection
      of ~2 * 10(5) plaque forming units of parental A7(74) strain. RESULTS: VA7-EGFP
      was able to replicate in and kill both canine cancer cell lines tested. No
      adverse events were observed in either of the two virus-injected adult Beagles
      and no infective virus could be recovered from any of the biological samples
      collected over the course of the study. Neutralizing antibodies to Semliki Forest
      virus became detectable in the dogs at 5 days post infection and remained
      elevated until study termination. CONCLUSIONS: Based on these results, testing of
      the oncolytic potential of attenuated Semliki Forest virus in canine cancer
      patients appears feasible.

PMID- 26215395
TI  - Effectiveness and Safety of Autologous Bone Marrow Stromal Cells Transplantation
      After Ischemic Stroke: A Meta-Analysis.
AB  - BACKGROUND: Autologous bone marrow stromal cells (BM-SCs) transplantation might
      be a potential therapy for stroke. Although a series of clinical trials were
      performed to assess the effectiveness and safety of BM-SCs transplantation after
      ischemic stroke, the results are still conflicting. This study aimed to pool
      previous controlled trials to assess the effectiveness of BM-SCs-based cell
      therapy after ischemic stroke. MATERIAL AND METHODS: Relevant studies were
      searched among online databases. Barthel index (BI) or modified Barthel index
      (mBI), National Institutes of Health Stroke Scale (NIHSS), and Rankin Score (mRS)
      were used to assess therapeutic effects. The frequencies of adverse events were
      extracted for assessing safety of stem cell therapy. Data analysis was performed
      by using Review Manager 5.3. RESULTS: Patients who received cell therapy had
      significantly lower NIHSS score (-1.85) than the controls. In addition, there
      might be some benefits in daily activity measured by mBI, but this meta-analysis
      failed to demonstrate significant benefits of BM-SCs-based cell therapy in
      increasing the proportion of mRS <=2 patients. We did not find any severe adverse
      events associated with BM-SCs-based cell therapy. CONCLUSIONS: Although BM
      MNCs/MSCs transplantation might generate some benefits in lowering the grade of
      impairment caused by ischemic stroke, large RCTs are required to further confirm
      the effectiveness of BM-MSCs/MNCs-based cell therapy and to optimize the
      conditions require for best therapeutic effects.

PMID- 26215396
TI  - The effect of short-term high versus normal protein intake on whole-body protein
      synthesis and balance in children following cardiac surgery: a randomized double
      blind controlled clinical trial.
AB  - BACKGROUND: Infants undergoing cardiac surgery are at risk of a negative protein
      balance, due to increased proteolysis in response to surgery and the
      cardiopulmonary bypass circuit, and limited intake. The aim of the study was to
      quantify the effect on protein kinetics of a short-term high-protein (HP) diet in
      infants following cardiac surgery. METHODS: In a prospective, double-blinded,
      randomized trial we compared the effects of a HP (5 g . kg(-1) . d(-1)) versus
      normal protein (NP, 2 g . kg(-1) . d(-1)) enteral diet on protein kinetics in
      children <24 months, on day 2 following surgical repair of congenital heart
      disease. Valine kinetics and fractional albumin synthesis rate (FSRalb) were
      measured with mass spectrometry using [1-(13)C]valine infusion. The Mann-Whitney
      U test was used to investigate differences between group medians. Additionally,
      the Hodges-Lehmann procedure was used to create a confidence interval with a
      point estimate of median differences between groups. RESULTS: Twenty-eight
      children (median age 9 months, median weight 7 kg) participated in the study, of
      whom in only 20 subjects isotopic data could be used for final calculations. Due
      to underpowering of our study, we could not draw conclusions on the primary
      outcome parameters. We observed valine synthesis rate of 2.73 (range: 0.94 to
      3.36) and 2.26 (1.85 to 2.73) MUmol . kg(-1) . min(-1) in the HP and NP diet,
      respectively. The net valine balance was 0.54 (-0.73 to 1.75) and 0.24 (-0.20 to
      0.63) MUmol . kg(-1) . min(-1) in the HP and NP group. Between groups, there was
      no difference in FSRalb. We observed increased oxidation and BUN in the HP diet,
      compared to the NP diet, as a plausible explanation of the metabolic fate of
      surplus protein. CONCLUSIONS: It is plausible that the surplus protein in the HP
      group has caused the increase of valine oxidation and ureagenesis, compared to
      the NP group. Because too few patients had completed the study, we were unable to
      draw conclusions on the effect of a HP diet on protein synthesis and balance. We
      present our results as new hypothesis generating data. TRIAL REGISTRATION: Dutch
      Trial Register NTR2334.

PMID- 26215398
TI  - Quality Management in Epileptology: Can It Really Improve Care for Patients?

PMID- 26215397
TI  - Exposure to cooking fuels and birth weight in Lanzhou, China: a birth cohort
      study.
AB  - BACKGROUND: Early studies have suggested that biomass cooking fuels were
      associated with increased risk of low birth weight (LBW). However it is unclear
      if this reduced birth weight was due to prematurity or intrauterine growth
      restriction (IUGR). METHODS: In order to understand the relationship between
      various cooking fuels and risk of LBW and small for gestational age (SGA), we
      analyzed data from a birth cohort study conducted in Lanzhou, China which
      included 9,895 singleton live births. RESULTS: Compared to mothers using gas as
      cooking fuel, significant reductions in birth weight were observed for mothers
      using coal (weight difference = 73.31 g, 95 % CI: 26.86, 119.77) and biomass
      (weight difference = 87.84 g, 95 % CI: 10.76, 164.46). Using biomass as cooking
      fuel was associated with more than two-fold increased risk of LBW (OR = 2.51, 95
      % CI: 1.26, 5.01), and the risk was mainly seen among preterm births (OR = 3.43,
      95 % CI: 1.21, 9.74). No significant associations with LBW were observed among
      mothers using coal or electromagnetic stoves for cooking. CONCLUSIONS: These
      findings suggest that exposure to biomass during pregnancy is associated with
      risk of LBW, and the effect of biomass on LBW may be primarily due to prematurity
      rather than IUGR.

PMID- 26215399
TI  - A New Concept of Health Can Improve the Definition of Frailty.
AB  - Following a newly developed concept of health, this viewpoint suggests that the
      concept of frailty can usefully be defined as: the weakening of health, i.e. the
      resilience or capacity to cope, and to maintain and restore one's integrity,
      equilibrium, and sense of wellbeing in three domains: physical, mental, and
      social. 

PMID- 26215400
TI  - Intrahepatic cholestasis of pregnancy: observational study of the treatment with
      low-dose ursodeoxycholic acid.
AB  - BACKGROUND: To exam the biochemical, obstetric management and pregnancy outcome
      in women with intrahepatic cholestasis of pregnancy (ICP) and treatment with
      ursodeoxycholic acid (UDCA). METHODS: Pregnancy outcome in patients with ICP (N =
      307) was studied and patients treated with UDCA (N = 208) vs. no UDCA were
      compared. The data of the antenatal visits, deliveries and neonatal outcome of
      307 pregnancies with ICP was collected from the hospital computerized delivery
      room log book. UDCA was used in 208 pregnancies. The diagnosis was made by
      maternal pruritus and elevation of total fasting bile acid (BA) (>6 MUmol/l) and
      elevation of serum alanine aminotransferases (ALT) (>45 U/l). Maternal and
      neonatal data was analysed and data of the patients who used UDCA during
      pregnancy was analysed separately and compared with the data from patients
      without medication. RESULTS: UDCA was well tolerated. Mothers receiving UDCA had
      ICP diagnosed five weeks earlier than mothers without medication. At the
      diagnosis, levels of total BA and ALT were higher in the group using UDCA
      compared to the group without medication. Most deliveries were induced and
      perinatal outcome was good. Apgar scores at 5 min were significantly lower in
      UDCA group (p < 0.05), but fetal umbilical artery pH values were similar in both
      groups (p > 0.05). There were 30 patients with total BA > 40 MUmol/l at
      diagnosis, 24 with UDCA and 6 without medication and those deliveries were
      induced soon after diagnosis. The preterm labour was also more common in these
      patents (p < 0.05). Women with preterm babies had significantly early onset
      pruritus and ICP was diagnosed earlier. Serum ALT and total BA levels were
      significantly higher in those pregnancies at diagnosis and also at first control.
      CONCLUSIONS: Preterm labour was associated in severe ICP (total BA > 40 MUmol/l),
      ALT levels were also significantly higher and ICP was diagnosed earlier (p <
      0.05). Apgar scores were lower in preterm babies (p < 0.05), but umbilical artery
      pHvalues were not significantly lower. UDCA was well tolerated by pregnant women.
      With low-dose UDCA treatment the obstetric outcome was good. We still recommend
      careful obstetrical follow-up.

PMID- 26215401
TI  - Review: animal models as a tool to dissect pivotal pathways driving
      spondyloarthritis.

PMID- 26215402
TI  - Association of Extubation Failure and Functional Outcomes in Patients with Acute
      Neurologic Illness.
AB  - BACKGROUND: An association between extubation failure and neurologic and
      functional outcomes in patients with primary neurologic illness has not been
      investigated rigorously. We plan to conduct a retrospective chart review to study
      this association. METHODS: A total of 949 unique patients intubated and
      ventilated for at least 48 h in Neuro ICU (NICU) were obtained. Extubation
      failure was defined as need for reintubation within 48 h of initial extubation.
      Independent and dependent association between extubation failure and clinical
      parameters was assessed. RESULTS: The patients had a median age [interquartile
      range (IQR)] of 58.5 (23.0) years. 60.5% were male and 81.9% were Caucasian.
      Extubation failure occurred in 108 (12.8%) patients. There was no difference in
      age, APACHE 3 score, FOUR score, or GCS score of patients at ICU admission
      between those who experienced extubation failure and those who did not.
      Extubation failure was associated with longer NICU and hospital LOS [median
      (IQR); 13.7 (11.3) vs. 9.1(8.2) days, P < 0.01 and 24.5 (20.0) vs. 16.8 (16.7)
      days, P < 0.01]. Patients with extubation failure had worse functional outcomes
      at 6 months as measured by the modified Rankin score [MRS; median (IQR), 5.0
      (2.0) vs. 4.0 (3.0), P < 0.01]. After adjusting for confounders, extubation
      failure was associated with longer hospital and ICU LOS and worse functional
      outcomes. CONCLUSIONS: In patients with acute neurological illness, extubation
      failure is associated with longer ICU and hospital stays but does not impact
      hospital mortality. Patients with extubation failure may experience a worsening
      of their functional status over time.

PMID- 26215403
TI  - Thymoquinone enhances cisplatin-response through direct tumor effects in a
      syngeneic mouse model of ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy
      characterized by the frequent development of resistance to platinum chemotherapy.
      Finding new drug combinations to overcome platinum resistance is a key clinical
      challenge. Thymoquinone (TQ) is a component of black seed oil that exerts
      multiple anti-tumorigenic effects on cells, including inhibition of NF-kappaB and
      promotion of DNA damage. We aimed to determine whether TQ enhances cisplatin
      cytotoxicity in cultured ovarian cancer cells and in an established murine
      syngeneic model of ovarian cancer. METHODS: Ovarian cancer cell viability in
      vitro was measured by sulforhodamine B (SRB) assays, and drug interactions tested
      for synergism by isobologram analysis. ID8-NGL mouse ovarian cancer cells stably
      expressing an NF-kappaB reporter transgene were injected intra-peritoneally into
      C57BL/6 mice. After 30 day TQ and/or cisplatin treatment, we measured the
      following indices: tumor burden (ascites volume, number of peritoneal implants
      and mesenteric tumor mass); NF-kappaB reporter activity (luciferase assay);
      protein expression of the double-strand DNA break marker, pH2AX(ser139), the
      proliferation markers, Ki67/mib-1 and PCNA, and the apoptosis markers, cleaved
      caspase-3, cleaved PARP and Bax; and mRNA expression of NF-kappaB targets, TNF
      alpha and IL-1beta. Two-tailed Mann-Whitney tests were used for measuring
      differences between groups in mouse experiments. RESULTS: In SRB assays, TQ and
      cisplatin synergized in ID8-NGL cells. In mice, cisplatin significantly reduced
      cell proliferation and increased apoptosis in tumors, resulting in decreased
      overall tumor burden. Combining TQ with cisplatin further decreased these
      indices, indicating co-operative effects between the drugs. TQ treatment promoted
      cisplatin-induced pH2AX expression in cultured cells and in tumors. While NF
      kappaB inhibition by TQ induced anti-tumor effects in vitro, we made the
      unexpected observation that TQ alone increased both tumor NF-kappaB activity and
      formation of ascites in vivo. CONCLUSIONS: TQ enhanced cisplatin-mediated
      cytoxicity in ovarian cancer cells in vitro and in a mouse syngeneic model,
      effects associated with increased DNA damage. However, our results strongly
      caution that TQ treatment alone may have an overall deleterious effect in the
      immunocompetent host through stimulation of ascites. Since TQ is a potential
      candidate for future clinical trials in ovarian cancer patients, this finding has
      considerable potential relevance to the clinic.

PMID- 26215405
TI  - Is near-infrared spectroscopy clinically useful in the preterm infant?
AB  - Near-infrared spectroscopy (NIRS) has been used to study cerebral haemodynamics
      and oxygenation in the preterm infant for many years, but its use as a clinical
      tool has remained elusive. This has partly been due to the challenges of
      providing a continuous quantitative measurement that is valid and reliable, as
      well as demonstrating that interventions based on NIRS measurements improve
      clinical outcome. Recent studies investigating cerebral oxygenation targeted
      treatment, and defining optimal blood pressure based on an assessment of
      cerebrovascular reactivity, suggest ways in which this technology may yet be
      clinically useful. 

PMID- 26215404
TI  - The remaining dentin thickness investigation of the attempt to remove broken
      instrument from mesiobuccal canals of maxillary first molars with virtual
      simulation technique.
AB  - BACKGROUND: To investigate differences in the estimated minimum remaining dentin
      thickness (RDT) between periapical radiographs using the paralleling and parallax
      technique, after simulated removal of broken instrument from the mesiobuccal (MB)
      canal of maxillary first molar in virtual simulation model. The 3D measurement
      was taken as the standard for comparison. METHODS: Thirty-six maxillary first
      molars were scanned by micro-CT and reconstructed as 3-dimensional (3D) model. A
      virtual fragment of an instrument was created within the MB canal in software.
      Removal of the broken instrument was simulated in both the 3D and 2D dataset.
      Then, the models of all specimens were submitted to 2D and 3D measurements for
      the lowest (RDT) value in each. Differences in the values between the paralleling
      and parallax radiographic technique and the 3D-RDT value were analyzed with two
      way Analysis of Variance. The Intra-class Correlation Coefficient (ICC) was used
      to assess consistency of the RDT measurements between the two periapical
      radiographic and techniques and 3D analysis. RESULTS: There was significant
      difference between RDT value obtained from the paralleling technique and 3D-RDT.
      There were no differences between RDT obtained from parallax (angled) technique
      and 3D-RDT. The ICC of RDT values between paralleling technique and 3D
      measurement were lower than 0.75. ICC between angled radiographs and 3D technique
      was close to 0.75. The optimal horizontal angle for the parallax technique was
      about 21 degrees . CONCLUSIONS: The virtual simulation technique can provide
      valuable insight into the benefit/risk analysis before removal of a broken
      instrument. Parallel radiographs overestimate the actual remain dentin thickness
      in mesiobuccal canals of maxillary first molars, whereas the parallel technique
      would give a closer estimate to the actual thickness at a projection angle of
      about 21 degrees .

PMID- 26215406
TI  - Personality of adults who were born very preterm.
AB  - OBJECTIVES: To examine very preterm (gestational age at birth <32 weeks) and/or
      very low birth weight (birth weight <1500 g: VP/VLBW) adults' personality and
      risk taking when compared with term controls. To investigate whether differences
      between VP/VLBW adults and controls remain after taking their general cognitive
      abilities into account. DESIGN: The Bavarian Longitudinal Study is a
      geographically defined prospective cohort study of neonatal at-risk children born
      in 1985/1986 in Germany. A total of 200 VP/VLBW and 197 controls completed main
      outcome measures including broad autism phenotype, personality traits (eg,
      introversion, neuroticism), and risk taking at 26 years of age. RESULTS: When
      compared with term controls, VP/VLBW adults scored significantly higher in
      autistic features, introversion and neuroticism but not in conscientiousness and
      closeness scales. They also reported lower risk taking. Profile analysis showed
      higher introversion, autistic features and neuroticism and lower risk taking as
      unique features of VP/VLBW adults (F(within-group)=0.81, ns; F(between
      group)=49.56, p<0.001). These characteristics were found to load onto a single
      profile factor which was equivalent between the VP/VLBW and control samples
      (chi(2)=12.49, df=7, ns; comparative fit index=0.98). VP/VLBW birth significantly
      predicted the profile factor (beta=0.33, p<0.001) and explained 11% of its
      variance. Adjusting for general cognitive deficits did not alter the findings.
      CONCLUSIONS: VP/VLBW birth poses an important risk for a global withdrawn
      personality, as indicated by being less socially engaged (introversion), low in
      taking risks, poor in communication (autistic features) and easily worried
      (neuroticism). This profile might help to explain the social difficulties VP/VLBW
      individuals experience in adult roles, such as in peer/partner relationships and
      career.

PMID- 26215407
TI  - [Angiotensin converting enzyme: the antigenic properties of the domain, role in
      Alzheimer's disease and tumor progression].
AB  - Angiotensin converting enzyme (ACE, EC 3.4.15.1) was discovered and characterized
      in the Laboratory of biochemistry and chemical pathology of proteins under the
      direction of academician V.N. Orekhovich, where its physiological function,
      associated with a key role in the regulation of the renin-angiotensin (RAS) and
      the kallikrein-kinin systems that control blood flow in the body and homeostasis
      was first deciphered. We carried out a search for structural differences between
      the two highly homologous domains (N- and C-domains) of somatic ACE (sACE); it
      was based on a comparative analysis of antigenic determinants (or B-epitopes) of
      both domains. The revealed epitopes were classified with variable and conserved
      regions and functionally important sites of the molecule ACE. Essential
      difference was demonstrated between locations of the epitopes in the N- and C
      domains. These data indicate the existence of structural differences between the
      domains of sACE. We studied the role of the domains of ACE in the metabolism of
      human amyloid beta peptide (Ab) - the main component of senile plaques, found in
      the brains of patients with Alzheimer's disease (AD). Our results demonstrated
      that only N-domain ACE cleaved the Ab between residues R5-H6, while, the C-domain
      of ACE failed to hydrolyze this region. In addition, the effect of post
      translational modifications of Ab on its hydrolysis by the ACE was investigated.
      We show that isomerization of residue D7, a common non-enzymatic age-related
      modification found in AD-associated species, does not reduce the affinity of the
      peptide to the N-domain of ACE, and conversely, it increases. According to our
      data, the role of ACE in the metabolism of Ab becomes more significant in the
      development of AD. RAS is involved in malignant transformation and tumor
      progression. RAS components, including ACE and angiotensin II receptors type 1
      (AT1R) are expressed in various human tumors. We found a significant increase in
      the level of ACE activity in the tumor tissue of squamous cell carcinoma of the
      cervix. In our viewpoint, the increase in ACE activity may be a marker of poor
      clinical prognosis. 

PMID- 26215408
TI  - [Bacterial recombinant L-asparaginases: properties, structure and anti
      proliferative activity].
AB  - For more than 40 years L-asparaginases are used in combined therapy of acute
      lymphoblastic leukemia in children and the range of tumors sensitive to these
      enzymes constantly extends. This review summarizes results of studies aimed at
      creation of new systems for heterological expression of bacterial L-asparaginases
      as Erwinia carotovora (EwA), Helicobacter pylori (HpA), Yersinia
      pseudotuberculosis (YpA) and Rhodospirillum rubrum (RrA); special attention is
      paid to isolation of purified enzymes and their crystallization, modification by
      chitosan/polyethylene, physicochemical, kinetic and structural properties
      characterization, and the study of the cytotoxic or anti-proliferative activity
      of new recombinant L-asparaginases on cell cultures in vitro. The resultant
      recombinant L-asparaginases (EwA, YpA, HpA i RrA) exhibit reasonable cytotoxic
      action on the human leukemia cells comparable to the pharmacologically available
      L-asparaginase EcA and represent practical interest in respect to creation, on
      their basis, new effective antineoplastic remedies. Further prospects of
      researches on bacterial L-asparaginases are associated with development of
      analogs of Rhodospirillum rubrum L-asparaginase (RrA) by means of directed
      changes of the protein structure using genetic engineering, development of chito
      PEGylation for receiving L-asparaginase preparations with improved
      pharmacokinetic characteristics. 

PMID- 26215409
TI  - [Molecularly imprinted polymers in electro analysis of proteins].
AB  - In the review the main approaches to creation of recognition materials capable of
      competing with biological specific receptors, (polymeric analogs of antibodies or
      molecularly imprinted polymers, MIP) for the electro analysis of functionally
      significant proteins such as a myoglobin, troponin T, albumin, human ferritin,
      calmodulin are considered. The main types of monomers for MIP fabrication, and
      methods for MIP/protein interactions, such as a surface plasmon resonance (SPR),
      nanogravimetry with use of the quartz crystal resonator (QCM), spectral and
      electrochemical methods are discussed. Experimental data on electrochemical
      registration of a myoglobin using MIP/electrode are presented. For a development
      of electrochemical sensor systems based on MIPs, o-phenylenediamine (1,2
      diaminobenzene was used as a monomer. It was shown that the imprinting factor
      Imax(MIP)/Imax(NIP), calculated as a myoglobin signal ratio when embedding in MIP
      to a myoglobin signal when embedding in the polymer received without molecular
      template (NIP) corresponds 2-4. 

PMID- 26215410
TI  - [Hedgehog signaling in the pathogenesis of neuro-oncology diseases].
AB  - The review summarizes current knowledge on the Hedgehog signaling pathway, its
      role in normal embryogenesis and/or initiation and progression of neuro
      oncological diseases, especially of high-grade gliomas, the most malignant
      neuroepithelial tumors. The main proteins forming the Hedgehog signaling pathway
      include Shh, PTCH1, SMO, HHIP, SUFU and GLI1 isoforms. Effects of other signaling
      pathways on the family of transcription factors GLI and other proteins are
      described. The review summarizes modern data about the impact of the Hedgehog
      signaling pathway on proliferation, migration activity and invasiveness, and also
      on tumor neoangiogenesis and tumor cell chemoresistance. The role of the Hedgehog
      signaling pathway in origin of cancer stem cells and epithelial-mesenchymal
      transition is also analyzed. Some prospects for new anticancer drugs acting on
      components of the Hedgehog signaling pathway inhibitors are demonstrated. 

PMID- 26215411
TI  - [The influence of doxorubicin incorporated in phospholipid drug delivery
      nanosystem on HEPG2 cells proteome].
AB  - A phospholipid drug delivery nanosystem with particle size up to 30 nm elaborated
      at the Institute of Biomedical Chemistry has been used earlier for incorporation
      of doxorubicin (Doxolip). This system demonstrated higher antitumor effect in
      vivo as compared with free doxorubicin. In this study the effect of this
      nanosystem containing doxorubicin on HepG2 cell proteome has been investigated.
      Cells were incubated in a medium containing phospholipid nanoparticles (0.5 mg/ml
      doxorubicin, 10 mg/mL phosphatidylcholine). After incubation for 48 h their
      survival represented 10% as compared with untreated cells. Cell proteins were
      analyzed by quantitative two-dimensional gel electrophoresis followed by
      identification of differentially expressed proteins with MALDI-TOF mass
      spectrometry. The phospholipid transport nanosystem itself insignificantly
      influenced the cell proteome thus confirming previous data on its safety.
      Doxorubicin, as both free substance and Doxolip (i.e. included into phospholipid
      nanoparticles) induced changes in expression of 28 proteins. Among these proteins
      only four of them demonstrated different in response to the effect of the free
      drug substance and Doxolip. Doxolip exhibited a more pronounced effect on
      expression of certain proteins; the latter indirectly implies increased
      penetration of the drug substance (included into nanoparticles) into the tumor
      cells. Increased antitumor activity of doxorubicin included into phospholipid
      nanoparticles may be associated with more active increase of specific protein
      expression. 

PMID- 26215412
TI  - [Analysis of proteomic profile changes of zebrafish embryos during exposure to
      doxorubicin, built-in the phospholipid transport nanosystem].
AB  - The proteome profile of Danio rerio embryos grown in the medium containing
      doxorubicin, included in the phospholipid transport nanosystem (doxolip) has been
      investigated using combination of 1D-electrophoresis with subsequent MALDI-TOF
      PMF mass spectrometry. Cultivation of growing of D. rerio embryos in the medium
      with doxolip caused a substantial increase in expression of the cytoskeletal
      proteins, a decrease in the number of nuclear proteins involved in DNA and RNA
      synthesis and disappearance of vitellogenin 2 in comparison with control (the
      cultivation medium containing the phospholipid transport nanosystem). Analysis of
      the proteomic profiles of doxolip-treated embryos suggests lower toxicity of
      doxorubicin incorporated in the phospholipid nanosystem. 

PMID- 26215413
TI  - [Allele polymorphism analysis in coagulation factors F2, F5 and folate metabolism
      gene MTHFR by using microchip-based multiplex real time PCR].
AB  - Single nucleotide polymorphism (SNP) genotyping methods are widely used for the
      detection of hereditary thrombophilias caused by genetic defects in the
      coagulation system. The hereditary thrombophilias are frequently associated with
      higher incidences of point mutations in hemostasis (F2 20210G>A, F5 1691G>A) and
      folate metabolism (MTHFR 677C>T, MTHFR 1298A>C) genes. Moreover, the combination
      of gene abnormalities in F2 or/and MTHFR with F5 Leiden mutation leads to
      increased risk of developing thrombosis. Thus, simultaneous detection of the
      multiple gene mutations in a sample has important clinical relevance. The
      microchip-based multiplex real time PCR for estimation of allele specific
      polymorphism in hemostatic and folate metabolism genes presented here has a high
      efficiency and may be used for laboratory diagnosis. The optimized protocol for
      estimation of 4 different types of genetic polymorphisms allowed PCR to be
      performed with minimal quantity of DNA template and PCR reagents including Taq
      polymerase and a short-term thermocycling. 

PMID- 26215414
TI  - [Atomic force microscopy fishing of gp120 on immobilized aptamer and its mass
      spectrometry identification].
AB  - A method of atomic force microscopy-based fishing (AFM fishing) has been
      developed for protein detection in the analyte solution using a chip with an
      immobilized aptamer. This method is based on the biospecific fishing of a target
      protein from a bulk solution onto the small AFM chip area with the immobilized
      aptamer to this protein used as the molecular probe. Such aptamer-based approach
      allows to increase an AFM image contrast compared to the antibody-based approach.
      Mass spectrometry analysis used after the biospecific fishing to identify the
      target protein on the AFM chip has proved complex formation. Use of the AFM chip
      with the immobilized aptamer avoids interference of the antibody and target
      protein peaks in a mass spectrum. 

PMID- 26215415
TI  - [Cytokines neuroinflammatory reaction to the action of homoaggregatic and
      liposomal forms of b-amyloid 1-40 in rats].
AB  - An injection model of preclinical stages of Alzheimer's disease has been
      reproduced in rats. It was accompanied by the decrease in the latent period of
      conditioned reflex avoidance, increasing levels of endogenous b-amyloid peptide 1
      40 and activation of inflammatory cytokines (IL-1b, TNF-a, IL-6, IL-10) in the
      cerebral cortex, hippocampus and blood serum of experimental animals. We belive
      that changes identified at the biochemical level are prerequisite to modulate
      neuronal functions in rats induced by Ab40_Human administration. The toxic effect
      of exogenous b-amyloid 1-40 homoaggregates caused intense response of the
      cytokine system, while its liposomal form caused the soft information signal to
      the activation of innate immunity. 

PMID- 26215416
TI  - [Effects of berberine on the recovery of rat liver xenobiotic-metabolizing
      enzymes after partial hepatectomy].
AB  - We have studied the effect of berberine on the recovery processes of liver
      xenobiotic-metabolizing function during its compensatory growth after 70% partial
      hepatectomy. It was found the hepatic ability to metabolize foreign substances
      are not restored up to day 8. Administration of berberine (10 mg/kg
      intraperitoneally) for 6 days led to normalization of both cytochrome P450
      dependent and flavin-containing monooxygenases. It is suggested that in the
      biotransformation of berberine involved not only cytochrome P450, but also flavin
      containing monooxygenases. 

PMID- 26215417
TI  - [Role of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) in the obtaining
      of stabilized magnetite nanoparticles for biomedical application].
AB  - Magnetite nanoparticles (NPs) are studied as agents for magnetic resonance
      imaging, hyperthermia of malignant tumors, targeted drug delivery as well as anti
      anemic action. One of the main problems of such NPs is their aggregation that
      requires creation of methods for magnetite NPs stabilization during preparation
      of liquid medicinal forms on their basis. The present work is devoted to the
      possibility of mexidol (2-ethyl-6-methyl-3-hydroxypyridine succinate) use for
      solubilization of magnetite NPs in hydrophilic medium. For this purpose, the
      condensate produced by electron-beam evaporation and condensation, with magnetite
      particles of size 5-8 nm deposited into the crystals of sodium chloride were used
      in conjunction with substance of mexidol (2-ethyl-6-methyl-3-hydroxypyridine
      succinate), and low molecular weight polyvinylpyrrolidone (PVP). The NP
      condensate was dispersed in distilled water or PVP or mexidol solutions. NPs size
      distribution in the liquid phase of the systems was determined by photon
      correlation spectroscopy, iron (Fe) concentration was evaluated by atomic
      emission spectrometry. It is shown that in the dispersion prepared in distilled
      water, the major amount of NPs was of 13-120 nm in size, in mexidol solution -
      270-1700 nm, in PVP solution - 30-900 nm. In the fluid containing magnetite NPs
      together with mexidol and PVP, the main fraction (99.9%) was characterized by the
      NPs size of 14-75 nm with maximum of 25 nm. This system had the highest iron
      concentration: it was similar to that in the sample with mexidol solution and 6.6
      7.3 times higher than the concentration in the samples with distilled water or
      PVP. Thus, in the preparation of aqueous dispersions based on magnetite NPs
      condensate, mexidol provides a transition of Fe to the liquid phase in amount
      necessary to achieve its biological activity, and PVP stabilizes such modified
      NPs. 

PMID- 26215418
TI  - [Effect of the thyroid status on the proteinases/inhibitors system under stress].
AB  - The alarm-stage of stress reaction (an hour after the stress of swimming of rats
      in a cage during an hour) is characterized by the stimulation of trypsine-like
      activity (TLA) in the liver, and especially in the blood. At the resistance stage
      (48 hours after the stress) there is normalization of TLA in the blood and
      limitation of its growth in the liver. At the stage of exhaustion (an hour of
      stress during 10 days) the most significant increase of TLA in the liver and
      blood develops. Experimental hypothyroidism (25 mg/kg merkazolil within 20 days)
      per se causes a reduction of TLA, defines more pronounced stimulation of
      proteolysis in the alarm-stage, prevents its normalization at the resistance
      stage, and promotes its excessive activation at the stage of exhaustion.
      Introduction of small doses of L-thyroxine (1.5-3.0 g/kg during 28 days) does not
      affect the system of proteolysis, limitis the increase of TLA at the alarm- and
      exhaustion stages, prevents its stimulation at the resistance-stage. The
      dependence of the changes in the proteases/inhibitors system under stress from
      the level of iodine-containing thyroid hormones in the blood is due to their
      influence on the activity of endogenous proteinase inhibitors (a1-antitrypsin and
      a2-macroglobulin) and on the permeability of lysosomes membranes. 

PMID- 26215419
TI  - [Effect of melatonin on antioxidant enzyme activities in blood erythrocytes of
      rats during acute emotional stress].
AB  - The effect of the epiphyseal hormone melatonin on the activity of antioxidant
      enzymes, glutathione peroxidase (GPx), glutathione reductase (GR), and Cu/Zn
      superoxide dismutase (Cu/Zn-SOD) was studied in peripheral blood erythrocytes of
      behaviorally passive and active Wistar rats. Acute emotional stress was modeled
      by immobilization of animals for1 h with simultaneous electrocutaneous
      stimulation. Basal activity of antioxidant glutathione enzymes in erythrocytes of
      behaviorally passive rats was higher than that in active animals. Administration
      of melatonin (2 mg/kg, intraperitoneally) was accompanied by a decrease in the
      activity of GPx and GR in erythrocytes from non-stressed passive animals. After
      experimental stress, passive rats demonstrated a significant increase in the
      activity of Cu/Zn-SOD and GPx in peripheral blood erythrocytes. The absence of
      stress-induced changes in functional activity of antioxidant defense enzymes in
      the blood of behaviorally active animals suggests a relatively constant oxidative
      status of tissues in these animals under stress conditions. Melatonin
      administration had little effect on stress-induced changes in functional activity
      of the erythrocyte antioxidant system in passive rats. Active specimens
      pretreated with melatonin before stress exposure were characterized by activation
      of study antioxidant enzymes. Quantitative parameters of the erythrocyte
      antioxidant defense enzymes did not differ in behaviorally active and passive
      rats subjected to experimental stress after melatonin injection. Thus, exogenous
      melatonin abolishes differences in the activity of study antioxidant enzymes in
      erythrocytes of animals with different behavioral parameters under basal
      conditions and after experimental stress. In passive rats melatonin mainly
      reduced the initial tension of oxidative processes. By contrast, administration
      of this hormone to active specimens is followed by an increase in functional
      activity of the antioxidant enzyme system under conditions of acute stress. 

PMID- 26215420
TI  - [Intensity of apoptotic processes, aconitate hydratase activity and citrate level
      in patients with type 2 diabetes mellitus complicated steatohepatitis under
      application of epifamin at basic therapy].
AB  - DNA fragmentation, caspase-1 and caspase-3, aconitate hydratase (AH) activities,
      and citrate content have been investigated in the blood of patients with type 2
      diabetes mellitus complicated by steatohepatitis. These indicators of apoptotic
      processes intensity and oxidative stress development were estimated after basic
      treatment and a combined therapy including epifamin. Before treatment DNA
      fragmentation blood leukocytes, decrease of AH activity and increase of caspases
      activities in the serum of patients were detected. Treatment with epifamin
      provided more pronounced changes in the investigated parameters towards control
      values as compared to basis therapy. Epifamin caused a positive effect on the
      citrate content in the serum of patients. Epifamin inclusion to the basic therapy
      was accompanied by a more pronounced changes towards the normal values of such
      biochemical parameters as ALT, AST, b-lipoproteins, cholesterol, fasting glucose
      and postprandial glucose levels. All these changes may be obviously attributed to
      epifamin-induced correction of the melatonin level and manifestation of
      adaptogenic properties and antioxidant effects of the hormone. 

PMID- 26215421
TI  - Study of fluorescence interaction and conformational changes of bovine serum
      albumin with histamine H1 -receptor--drug epinastine hydrochloride by
      spectroscopic and time-resolved fluorescence methods.
AB  - The fluorescence, ultraviolet (UV) absorption, time resolved techniques, circular
      dichroism (CD), and infrared spectral methods were explored as tools to
      investigate the interaction between histamine H1 drug, epinastine hydrochloride
      (EPN), and bovine serum albumin (BSA) under simulated physiological conditions.
      The experimental results showed that the quenching of the BSA by EPN was static
      quenching mechanism and also confirmed by lifetime measurements. The value of n
      close to unity indicated that one molecule of EPN was bound to protein molecule.
      The binding constants (K) at three different temperatures were calculated (7.1 *
      10(4), 5.5 * 10(4), and 3.9 * 10(4) M(-1)). Based on the thermodynamic parameters
      (DeltaH(0), DeltaG(0), and DeltaS(0)), the nature of binding forces operating
      between drug and protein was proposed. The site of binding of EPN in the protein
      was proposed to be Sudlow's site I based on displacement experiments using site
      markers viz, warfarin, ibuprofen, and digitoxin. Based on the Forster's theory of
      non-radiation energy transfer, the binding average distance, r between the donor
      (BSA) and acceptor (EPN) was evaluated and found to be 4.48 nm. The UV-visible,
      synchronous fluorescence, CD, and three-dimensional fluorescence spectral results
      revealed the changes in secondary structure of the protein upon its interaction
      with EPN.

PMID- 26215422
TI  - Recruitment of cyanobacteria from the sediments in the eutrophic Shanzi
      Reservoir.
AB  - This study investigated the impact of four environmental factors on the
      recruitment of cyanobacteria from bottom sediments in the eutrophic Shanzi
      Reservoir. Temperature and light were identified as the key determinants for the
      recruitment of Microcystis and Oscillatoria. Cyanobacteria became dominant at
      higher temperature (20  degrees C) and light intensity (2000 lx) and Microcystis
      and Oscillatoria were the major species. Detailed recruitment simulation
      undertaken with the respective gradients of temperature and light suggested that
      both Microcystis and Oscillatoria are temperature sensitive and that their
      critical temperature point was 10  degrees C. However, distinct light impacts
      were observed only on Microcystis. The recruitment of Oscillatoria was light
      independent, whereas Microcystis had a positive relationship with light
      intensity. Physical disturbance promoted Microcystis recruitment and also
      affected the structure of the recruited cyanobacterial community at the water
      sediment interface, based on quantitative polymerase chain reaction (qPCR) and
      phylogenetic analysis.

PMID- 26215423
TI  - Genetic analysis reveals diversity and genetic relationship among Trichoderma
      isolates from potting media, cultivated soil and uncultivated soil.
AB  - BACKGROUND: Trichoderma is one of the most common fungi in soil. However, little
      information is available concerning the diversity of Trichoderma in soil with no
      previous history of cultivation. This study was conducted to investigate the most
      common species and the level of genetic relatedness of Trichoderma species from
      uncultivated soil in relation to cultivated soil and potting media. RESULTS: A
      total of 24, 15 and 13 Trichoderma isolates were recovered from 84 potting media
      samples, 45 cultivated soil samples and 65 uncultivated soil samples,
      respectively. Analysis based on the internal transcribed spacer region of the
      ribosomal RNA (rRNA) and the translation elongation factor gene (EF1) indicated
      the presence of 9 Trichoderma species: T. harzianum (16 isolates), T. asperellum
      (13), T. citrinoviride (9), T. orientalis (3), T. ghanense (3), T. hamatum (3),
      T. longibrachiatum (2), T. atroviride (2), and T. viride (1). All species were
      found to occur in potting media samples, while five Trichoderma species were
      recovered from the cultivated soils and four from the uncultivated soils. AFLP
      analysis of the 52 Trichoderma isolates produced 52 genotypes and 993 polymorphic
      loci. Low to moderate levels of genetic diversity were found within populations
      of Trichoderma species (H = 0.0780 to 0.2208). Analysis of Molecular Variance
      indicated the presence of very low levels of genetic differentiation (Fst =
      0.0002 to 0.0139) among populations of the same Trichoderma species obtained from
      the potting media, cultivated soil and uncultivated soil. CONCLUSION: The study
      provides evidence for occurrence of Trichoderma isolates in soil with no previous
      history of cultivation. The lack of genetic differentiation among Trichoderma
      populations from potting media, cultivated soil and uncultivated soil suggests
      that some factors could have been responsible for moving Trichoderma propagules
      among the three substrates. The study reports for the first time the presence of
      4 Trichoderma species in Oman: T. asperellum, T. ghanense, T. longibrachiatum and
      T. orientalis.

PMID- 26215424
TI  - Biochemical Characterization of the DASH-Type Cryptochrome CryD From Fusarium
      fujikuroi.
AB  - Proteins from the cryptochrome/photolyase family utilize UV-A, blue or even red
      light to achieve such diverse functions as repair of DNA lesions by photolyases
      and signaling by cryptochromes. DASH-type cryptochromes retained the ability to
      repair cyclobutane pyrimidine dimers (CPDs) in single-stranded DNA regions in
      vitro. However, most organisms possess conventional CPD photolyases responsible
      for repair of these lesions in vivo. Recent work showed that the DASH-type
      cryptochrome CryD plays a regulatory role in diverse light-dependent processes in
      Fusarium fujikuroi. Here, we report our in vitro studies on heterologously
      expressed FfCryD. The purified protein contains N(5) ,N(10) 
      methenyltetrahydrofolate and flavin adenine dinucleotide as cofactors.
      Photoreduction and DNA photorepair experiments confirmed that FfCryD is active in
      light-driven electron transfer processes. However, the protein showed comparable
      affinities for CPD-comprising and undamaged DNA probes. Surprisingly, after
      purification, full-length FfCryD as well as a truncated version containing only
      the PHR domain bound RNA which influenced their behavior in vitro. Moreover,
      binding of FfCryD to RNA indicates a putative role in RNA metabolism or in
      posttranscriptional control of gene expression.

PMID- 26215425
TI  - Decision-related action orientation predicts police officers' shooting
      performance under pressure.
AB  - BACKGROUND AND OBJECTIVES: We aimed to test whether police officers' trait self
      control strength decreases negative effects of high pressure (HP) on state
      anxiety, shooting behavior, and shooting performance. DESIGN AND METHODS: Forty
      two officers performed a shooting test under both high and low-pressure (LP)
      conditions. Self-control strength was assessed with the decision-related action
      orientation (AOD) scale of the Action Control Scale (ACS-90). Effects of AOD on
      perceived anxiety, heart rate, shooting time, and shot accuracy were estimated
      and controlled for those of other individual difference measures (i.e. age,
      police working experience, trait anxiety, and threat-related action orientation).
      RESULTS: After controlling for baseline values in the LP condition as well as the
      other individual difference measures, AOD significantly predicted shot accuracy
      in the HP condition. CONCLUSIONS: Results suggest that trait self-control
      strength in the form of AOD helps officers cope with anxiety and maintain
      perceptual-motor performance under HP.

PMID- 26215427
TI  - Recyclable Hypervalent-Iodine-Mediated Dehydrogenative alpha,beta'
      Bifunctionalization of beta-Keto Esters Under Metal-Free Conditions.
AB  - We have developed a method for recyclable hypervalent-iodine-mediated direct
      dehydrogenative alpha,beta'- bifunctionalization of beta-ketoesters and beta
      diketones under metal-free conditions, which affords a straightforward way to
      synthesize benzo-fused 2,3-dihydrofurans. This efficient, mild method, which has
      a wide substrate scope and good functional-group tolerance, was used for the
      multistep synthesis of the protected aglycone of a naturally occurring phenolic
      glycoside. A mechanism involving Michael addition to an enone intermediate and
      subsequent oxidative cyclization is proposed. 

PMID- 26215426
TI  - Health effects of the 2012 Valencia (Spain) wildfires on children in a cohort
      study.
AB  - In July 2012, two simultaneous wildfires burnt a big area in Valencia (Spain),
      where a birth cohort study (INMA) is being developed. The heavy smoke covered the
      whole INMA study area for several days. We aimed at evaluating the 2012 Valencia
      wildfire effects on the health of children enrolled in the INMA-Valencia cohort.
      Two weeks after the extinction of the wildfires, a phone survey was conducted and
      finally 460 individuals were enrolled. We considered a wildfire period (12-day
      interval when they were active) and a control period (12-day interval just before
      wildfires). Parents were asked about respiratory symptoms experienced during both
      periods, and during wildfires only about the preventive measures adopted and the
      perception of exposure, along with individual data collected through the
      different follow-up surveys of the cohort. Conditional logistic regression models
      were applied, and we included interaction terms for asthma/rhinitis and level of
      perception of exposure; 82.4 % perceived smoke smell outdoors, 40 % indoors and
      more than 90 % of the families observed the presence of ash. An adjusted odds
      ratio of 3.11 [95 % confidence interval 1.62-5.97] for itchy/watery eyes and 3.02
      [1.41-6.44] for sore throat was obtained. Significant interaction terms for
      rhinitis and asthma in itchy/watery eyes and sneezing, and only asthma for sore
      throat were obtained. Exposure to wildfire smoke was associated with increased
      respiratory symptoms in this child population, particularly affecting susceptible
      individuals with asthma or rhinitis. 

PMID- 26215428
TI  - Usefulness of in-house PCR methods for hepatitis B virus DNA detection.
AB  - The aim of the present study was to evaluate the performance of three in-house
      PCR techniques for HBV DNA detection and compare it with commercial quantitative
      methods to evaluate the usefulness of in-house methods for HBV diagnosis. Three
      panels of HBsAg reactive sera samples were evaluated: (i) 50 samples were
      examined using three methods for in-house qualitative PCR and the Cobas Amplicor
      HBV Monitor Assay; (ii) 87 samples were assayed using in-house semi-nested PCR
      and the Cobas TaqMan HBV test; (iii) 11 serial samples obtained from 2 HBV
      infected individuals were assayed using the Cobas Amplicor HBV test and semi
      nested PCR. In panel I, HBV DNA was detected in 44 samples using the Cobas
      Amplicor HBV test, 42 samples using semi-nested PCR (90% concordance with Cobas
      Amplicor), 22 samples using PCR for the core gene (63.6% concordance) and 29
      samples using single-round PCR for the pre-S/S gene (75% concordance). In panel
      II, HBV DNA was quantified in 78 of the 87 HBsAg reactive samples using Cobas
      TaqMan but 52 samples using semi-nested PCR (67.8% concordance). HBV DNA was
      detected in serial samples until the 17th and 26th week after first donation
      using in-house semi-nested PCR and the Cobas Amplicor HBV test, respectively. In
      house semi-nested PCR presented adequate concordance with commercial methods as
      an alternative method for HBV molecular diagnosis in low-resource settings. 

PMID- 26215429
TI  - Functional ferroelectric tunnel junctions on silicon.
AB  - The quest for solid state non-volatility memory devices on silicon with high
      storage density, high speed, low power consumption has attracted intense research
      on new materials and novel device architectures. Although flash memory dominates
      in the non-volatile memory market currently, it has drawbacks, such as low
      operation speed, and limited cycle endurance, which prevents it from becoming the
      "universal memory". In this report, we demonstrate ferroelectric tunnel junctions
      (Pt/BaTiO3/La0.67Sr0.33MnO3) epitaxially grown on silicon substrates. X-ray
      diffraction spectra and high resolution transmission electron microscope images
      prove the high epitaxial quality of the single crystal perovskite films grown on
      silicon. Furthermore, the write speed, data retention and fatigue properties of
      the device compare favorably with flash memories. The results prove that the
      silicon-based ferroelectric tunnel junction is a very promising candidate for
      application in future non-volatile memories. 

PMID- 26215430
TI  - Extent, causes and impact of road traffic crashes in the Solomon Islands 1993
      2012: data from the orthopaedic department at the National Referral Hospital,
      Honiara.
AB  - INTRODUCTION: Road traffic crashes constitute a considerable public health burden
      and represent the eighth leading cause of death and tenth leading cause of
      disability adjusted life years (DALYs) globally. However, very little is known
      about the extent, causes and impact of crashes in low- and middle-income
      countries including those in the Pacific. This lack of data is particularly true
      for the Solomon Islands. METHODS: The study is a retrospective record review of a
      pre-existing, de-identified dataset. A standardised trauma form is completed for
      all patients presenting to the orthopaedic department at the National Referral
      Hospital in Honiara with a suspected fracture following a trauma. Data are coded
      using one of 27 unique codes. Data related to road traffic crashes were extracted
      from the larger dataset, cleaned and analysed in Microsoft Excel. RESULTS: The
      database contained 699 records coded with one of seven codes related to road
      traffic crashes. Patients in the database were most frequently injured whilst a
      passenger in a car (27.8%), as a pedestrian (24.0%), or as a passenger in an open
      truck (21.6%). Almost three-quarters of patients were male. Just under half
      (48.5%) were aged between 10 and 29 years. Alcohol was listed as a contributing
      factor in 23.8% of presentations. CONCLUSIONS: This is one of the first studies
      to provide data on road traffic crashes in the Solomon Islands. In this database,
      young males were most likely to be involved in a crash that resulted in a
      suspected fracture. Young males are in their prime years of productivity, and
      injuries that remove them from the workforce could have severe socioeconomic
      implications. This study found that more than half of injuries were borne by
      vulnerable road users such as pedestrians and motorcyclists, indicating a need
      for interventions that take these users into account. Finally, the study provides
      insight into the large impact that alcohol has on the risk of road traffic
      crashes.

PMID- 26215431
TI  - Interventions do not enhance medication persistence and compliance in patients
      with overactive bladder: a 24 weeks, randomised, open-label, multi-center trial.
AB  - OBJECTIVES: Anticholinergics are currently the mainstay for the management of
      overactive bladder (OAB). However, low drug adherence has been noted with these
      medications. The aim of this study was to determine whether a health education
      intervention (HEI) could improve drug persistence with anticholinergics in OAB
      patients. METHODS: We enrolled 682 OAB patients who were randomly distributed
      into either the HEI plus fesoterodine (HEI) group or the fesoterodine alone
      (control) group. The HEI consists of four education sections: understanding OAB
      disease, dietary control, bladder training and understanding anticholinergics.
      The primary end-point was the difference in drug persistence between the HEI and
      control groups at 24 weeks. Persistence was defined as a gap <= 30 days between
      successive prescription pills. RESULTS: Among the 682 patients, 210 (30.8%)
      completed 24 weeks of study. Persistence of the HEI group at 6 months was not
      statistically higher than that of the control group (40.4% vs. 34.9%, p = 0.181).
      Compliance at 6 months was also similar between the two groups (38.5% vs. 32.5%,
      p = 0.128). Using OAB symptom score questionnaire, the efficacy of the two groups
      was not different at each follow-up (p > 0.05). The global response was similar
      between the two groups. However, the HEI group was more satisfied with treatment
      than the control group (p = 0.034). The most common reason for discontinuation
      was satisfaction with the treatment so that they did not need to follow-up,
      followed by inadequate efficacy in both groups. Adverse events were reported in
      12.3% of patients. CONCLUSIONS: The health education intervention was not
      effective to increase drug persistence in OAB patients on anticholinergics.

PMID- 26215432
TI  - Joint action changes valence-based action coding in an implicit attitude task.
AB  - Recent studies suggest that co-acting with another person induces a problem to
      discriminate between one's own and the other's actions which can be resolved by
      emphasizing action features that discriminate best between both persons' actions
      in a given task context. Mostly, overt action features like the spatial position
      of responses have been suggested as discriminating action features. In the
      present study, we tested whether non-externally perceivable, covert action
      features can be used for resolving the action discrimination problem during joint
      action. Therefore, we compared task performance between a joint and an individual
      version of the Go/Nogo Association Task, a task requiring the association of a
      valence to the response. We found a larger implicit attitude effect in the joint
      than in the individual setting for person-related (self and other, Experiment 1)
      as well as for non-person-related attitude objects (fruit and insect, Experiment
      2) suggesting that the weight of valence information is increased in the internal
      coding of responses when valence discriminates between both responses. In
      contrast, we found a smaller implicit attitude effect in a person present setting
      than an individual setting (Experiment 3) indicating that the enhanced implicit
      attitude effect observed in the joint settings of Experiments 1 and 2 is not due
      to social facilitation. Our results suggest that action discrimination during
      joint action can rely on covert action features. The results are in line with the
      referential coding account, and specify the kind of action features that are
      represented when sharing a task with another person. 

PMID- 26215433
TI  - Proactive control of irrelevant task rules during cued task switching.
AB  - In task-switching paradigms, participants are often slower on incongruent than
      congruent trials, a pattern known as the task-rule congruency effect. This effect
      suggests that irrelevant task rules or associated responses may be retrieved
      automatically in spite of task cues. The purpose of the present study was to
      examine whether the task-rule congruency effect may be modulated via
      manipulations intended to induce variation in proactive control. Manipulating the
      proportion of congruent to incongruent trials strongly influenced the magnitude
      of the task-rule congruency effect. The effect was significantly reduced in a
      mostly incongruent list relative to a mostly congruent list, a pattern that was
      observed for not only biased but also 50 % congruent items. This finding
      implicates a role for global attentional control processes in the task-rule
      congruency effect. In contrast, enhancing the preparation of relevant (cued) task
      rules by the provision of a monetary incentive substantially reduced mixing costs
      but did not affect the task-rule congruency effect. These patterns support the
      view that there may be multiple routes by which proactive control can influence
      task-switching performance; however, only select routes appear to influence the
      automatic retrieval of irrelevant task rules. 

PMID- 26215434
TI  - Inducing attention not to blink: auditory entrainment improves conscious visual
      processing.
AB  - Our ability to allocate attention at different moments in time can sometimes fail
      to select stimuli occurring in close succession, preventing visual information
      from reaching awareness. This so-called attentional blink (AB) occurs when the
      second of two targets (T2) is presented closely after the first (T1) in a rapid
      serial visual presentation (RSVP). We hypothesized that entrainment to a rhythmic
      stream of stimuli-before visual targets appear-would reduce the AB. Experiment 1
      tested the effect of auditory entrainment by presenting sounds with a regular or
      irregular interstimulus interval prior to a RSVP where T1 and T2 were separated
      by three possible lags (1, 3 and 8). Experiment 2 examined visual entrainment by
      presenting visual stimuli in place of auditory stimuli. Results revealed that
      irrespective of sensory modality, arrhythmic stimuli preceding the RSVP triggered
      an alerting effect that improved the T2 identification at lag 1, but impaired the
      recovery from the AB at lag 8. Importantly, only auditory rhythmic entrainment
      was effective in reducing the AB at lag 3. Our findings demonstrate that
      manipulating the pre-stimulus condition can reduce deficits in temporal attention
      characterizing the human cognitive architecture, suggesting innovative trainings
      for acquired and neurodevelopmental disorders. 

PMID- 26215435
TI  - Continuation or discontinuation of pioglitazone when starting bedtime insulin in
      patients with poorly controlled type 2 diabetes in an inner-city population.
AB  - OBJECTIVE: We studied the impact of continuing versus discontinuing pioglitazone
      on hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and weight when starting
      bedtime insulin in patients with poor glycemic control. METHODS: We
      retrospectively analyzed data from a 13-month randomized control trial on 77
      patients with type 2 diabetes mellitus (DM), who despite maximum doses of three
      oral diabetes medications (metformin, sulfonylurea and pioglitazone) had HbA1C
      levels above 7.5%. Patients were randomized to either continuing or discontinuing
      pioglitazone in addition to starting and up-titrating bedtime insulin. HbA1C,
      FPG, and weight were assessed at baseline, 3months, 7months and 13months with the
      differences from baseline for the two groups compared at each of the three time
      points using the Wilcoxon rank sum test. RESULTS: We found that HbA1c was
      significantly lower at the 7-month (p=0.01) and 13-month time points (p=0.036),
      and FPG was significantly lower at all three time points in the group continuing
      pioglitazone compared with those discontinuing pioglitazone. Continuing
      pioglitazone resulted in a greater increase in weight at the 3-month (p=0.002), 7
      month (p=0.0001) and 13-month (p=0.00003) time points. Patients with the lowest
      HbA1c (<8.2%) at baseline were more likely to benefit from continuing
      pioglitazone than those with higher baseline HbA1c. Patients who started insulin
      and discontinued pioglitazone had similar HbA1c, FPG and weight at the three time
      points as at baseline, suggesting that pioglitazone and bedtime insulin has
      similar glycemic effect in this population. CONCLUSIONS: We conclude that in
      patients with uncontrolled type 2 DM, continuing pioglitazone while concurrently
      starting bedtime insulin within a 13-month period led to a significant decrease
      in both HbA1c and FPG levels compared with those who did not receive
      pioglitazone; however weight increased during this period.

PMID- 26215436
TI  - Prognostic significance of increased bone marrow microcirculation in newly
      diagnosed multiple myeloma: results of a prospective DCE-MRI study.
AB  - OBJECTIVES: Aim of this prospective study was to investigate prognostic
      significance of increased bone marrow microcirculation as detected by dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local
      complications in patients with multiple myeloma (MM). METHODS: We performed DCE
      MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data
      according to the Brix model to acquire amplitude A and exchange rate constant
      kep. In 61 patients a second MRI performed after therapy was evaluated to assess
      changes in vertebral height and identify vertebral fractures. RESULTS:
      Correlation analysis revealed significant positive association between beta2
      microglobulin as well as immunoparesis with DCE-MRI parameters A and kep.
      Additionally, A was negatively correlated with haemoglobin levels and kep was
      positively correlated with LDH levels. Higher baseline kep values were associated
      with decreased vertebral height in a second MRI (P = 0.007) and A values were
      associated with new vertebral fractures in the lower lumbar spine (P = 0.03 for
      L4). Pre-existing lytic bone lesions or remission after therapy had no impact on
      the occurrence of vertebral fractures. Multivariate analysis revealed that
      amplitude A is an independent adverse risk factor for overall survival.
      CONCLUSION: DCE-MRI is a non-invasive tool with significance for systemic
      prognosis and vertebral complications. KEY POINTS: * Qualitative parameters from
      DCE-MRI are correlated with established factors of disease activity * Increased
      marrow microcirculation might be a risk factor for loss of vertebral height and
      fractures * Amplitude A is an independent predictor for shortened overall
      survival.

PMID- 26215437
TI  - Toric Intraocular Lens Calculations Using Ratio of Anterior to Posterior Corneal
      Cylinder Power.
AB  - PURPOSE: To evaluate the accuracy of toric intraocular lens (IOL) calculation
      using estimated total corneal astigmatism based on the anterior-to-posterior
      corneal cylinder power ratio according to the axis orientation of anterior
      corneal astigmatism. DESIGN: Retrospective cross-sectional study. METHODS: Nine
      hundred twenty-eight eyes of 928 reference subjects and 20 cataract patients (20
      eyes) implanted with a toric IOL were enrolled. Linear regression analysis
      parameters (beta0 and beta1) of relationship between the simulated keratometry
      cylinder (CylSimK) and posterior corneal cylinder power of reference subjects
      were used to calculate the estimated posterior corneal astigmatism (-[beta1 *
      CylSimK + beta0] @ 90). When regression analysis was not significant, estimated
      posterior corneal astigmatism was defined as the negative value of the mean
      posterior corneal cylinder power @ 90. Estimated total corneal astigmatism was
      defined as the vectorial sum of anterior corneal astigmatism and estimated
      posterior corneal astigmatism. Residual astigmatism error, predicted using SimK,
      was compared with that predicted using estimated total corneal astigmatism.
      RESULTS: Estimated posterior corneal astigmatism was determined to be -(0.15 *
      CylSimK + 0.22) @ 90 in eyes with with-the-rule astigmatism, -(0.05 * CylSimK +
      0.27) @ 90 in oblique astigmatism, and -0.27 @ 90 in against-the-rule
      astigmatism. The median magnitude of the predicted residual astigmatism error
      calculated using estimated total corneal astigmatism (0.30 cylinder diopters) was
      significantly smaller than that calculated with SimK (0.50 cylinder diopters).
      CONCLUSIONS: Toric IOL calculations using estimated total corneal astigmatism
      based on the anterior-to-posterior corneal cylinder power ratio provided a more
      appropriate toric IOL cylinder power than calculations using SimK astigmatism.

PMID- 26215438
TI  - Torn between dual roles: the experiences of nurse-family members when a loved one
      is hospitalised in a critical condition.
AB  - AIMS AND OBJECTIVES: To understand and interpret the experiences of nurse-family
      members when a family member or loved one is hospitalised in a critical
      condition. BACKGROUND: Having a family member hospitalised with a critical
      illness is a traumatic stressor, often with long-term sequelae. Providing
      holistic care for family members who are also nurses makes the provision of care
      more complex because of their professional expertise; yet few studies have
      explored this issue. DESIGN: In this descriptive study, qualitative data were
      collected using a questionnaire and analysed using van Manen's (Researching Lived
      Experience: Human Science for an Action Sensitive Pedagogy, 1990, State
      University of New York Press, London, ON) six-step approach. METHODS: Twenty
      nurse-family members completed an online questionnaire in June 2013. Qualitative
      findings from 19 participants were included in the analysis. The phenomenological
      analysis approach described by van Manen (Researching Lived Experience: Human
      Science for an Action Sensitive Pedagogy, 1990, State University of New York
      Press, London, ON) was used to describe and interpret nurse-family member
      experiences. RESULTS: Nurse-family members experience significant dual role
      conflicts between their personal and professional personas due to their
      specialised knowledge, need for watchfulness and competing expectations. Our
      findings describe how dual role conflicts developed and were managed, and reveal
      the resultant emotional toll and psychological distress as nurse-family members
      struggled to resolve these conflicts. CONCLUSIONS: Nurse-family members require a
      different type of care than general public family members, yet their unique needs
      are often unmet, leading to increased anxiety and distress that could potentially
      be minimised. An increased awareness and emphasis on the nurse-family member
      experience can ensure health care professionals are better placed to provide
      appropriate and targeted care to minimise distressing dual role conflicts.
      RELEVANCE TO CLINICAL PRACTICE: There is a need for targeted and specialised
      communication appropriate to each nurse-family members' needs and level of
      understanding, and to clarify expectations to ensure nurse-family members'
      professional knowledge and skills are recognised and respected without being
      exploited.

PMID- 26215439
TI  - A genetically adjuvanted influenza B virus vector increases immunogenicity and
      protective efficacy in mice.
AB  - The existence of multiple antigenically distinct types and subtypes of influenza
      viruses allows the construction of a multivalent vector system for the mucosal
      delivery of foreign sequences. Influenza A viruses have been exploited
      successfully for the expression of extraneous antigens as well as
      immunostimulatory molecules. In this study, we describe the development of an
      influenza B virus vector whose functional part of the interferon antagonist NS1
      was replaced by human interleukin 2 (IL2) as a genetic adjuvant. We demonstrate
      that IL2 expressed by this viral vector displays immune adjuvant activity in
      immunized mice. Animals vaccinated with the IL2 viral vector showed an increased
      hemagglutination inhibition antibody response and higher protective efficacy
      after challenge with a wild-type influenza B virus when compared to mice
      vaccinated with a control virus. Our results demonstrate that it is feasible to
      construct influenza B vaccine strains expressing immune-potentiating foreign
      sequences from the NS genomic segment. Based on these data, it is now
      hypothetically possible to create a trivalent (or quadrivalent) live attenuated
      influenza vaccine in which each component expresses a selected genetic adjuvant
      with tailored expression levels. 

PMID- 26215440
TI  - Establishment of persistent foot-and-mouth disease virus (FMDV) infection in MDBK
      cells.
AB  - In addition to acute infection and disease, foot-and-mouth disease virus (FMDV)
      can cause persistent infection in ruminants. Such "carrier" animals represent a
      potential risk for FMDV transmission to susceptible animals. However, the
      mechanisms and the factors that determine FMDV persistence remain unknown. We
      describe here the establishment of FMDV type O persistent infection in a bovine
      epithelial cell line (Madin-Darby bovine kidney; MDBK). Preliminary experiments
      to assess the permissivity of MDBK cells to FMDV O infection revealed an unusual
      pattern of infection: after the initial phase of acute cell lysis, new monolayers
      formed within 48-72 h post-infection. We found that some cells survived cytolytic
      infection and subsequently regrew, thereby demonstrating that this bovine cell
      line can be persistently infected with FMDV type O. Further evidence that MDBK
      cells were persistently infected with FMDV includes: (i) detection of viral RNA
      in cells as well as in cell culture supernatants, (ii) detection of viral
      antigens in the cells by immunofluorescence analysis, and (iii) production of
      infectious viral particles for up to 36 cell passages. Furthermore, preliminary
      sequence analysis of persistent virus revealed a single nucleotide substitution
      within the VP1 coding region, resulting in the V50A amino acid substitution. This
      bovine model of FMDV persistence holds promise for the investigation of the viral
      and cellular molecular determinants that promote FMDV persistence. 

PMID- 26215441
TI  - Priming with two DNA vaccines expressing hepatitis C virus NS3 protein targeting
      dendritic cells elicits superior heterologous protective potential in mice.
AB  - Development an effective vaccine may offer an alternative preventive and
      therapeutic strategy against HCV infection. DNA vaccination has been shown to
      induce robust humoral and cellular immunity and overcome many problems associated
      with conventional vaccines. In this study, mice were primed with either
      conventional pVRC-based or suicidal pSC-based DNA vaccines carrying DEC-205
      targeted NS3 antigen (DEC-NS3) and boosted with type 5 adenoviral vectors
      encoding the partial NS3 and core antigens (C44P). The prime boost regimen
      induced a marked increase in antigen-specific humoral and T-cell responses in
      comparison with either rAd5-based vaccines or DEC-205-targeted DNA immunization
      in isolation. The protective effect against heterogeneous challenge was
      correlated with high levels of anti-NS3 IgG and T-cell-mediated immunity against
      NS3 peptides. Moreover, priming with a suicidal DNA vaccine (pSC-DEC-NS3), which
      elicited increased TNF-alpha-producing CD4+ and CD8+ T-cells against NS3-2
      peptides (aa 1245-1461), after boosting, showed increased heterogeneous
      protective potential compared with priming with a conventional DNA vaccine (pVRC
      DEC-NS3). In conclusion, a suicidal DNA vector (pSC-DEC-NS3) expressing DEC-205
      targeted NS3 combined with boosting using an rAd5-based HCV vaccine (rAd5-C44P)
      is a good candidate for a safe and effective vaccine against HCV infection. 

PMID- 26215442
TI  - First molecular detection and characterization of Akabane virus in small
      ruminants in Turkey.
AB  - Abortion outbreaks associated with congenital malformations in two distinct small
      ruminant flocks were reported in Turkey in 2013-2014. This paper describes the
      first molecular characterization of Turkish Akabane virus strains in small
      ruminant flocks using partial sequence analysis of the S segment and pathological
      findings. 

PMID- 26215443
TI  - Detection and molecular characterization of zoonotic viruses in swine fecal
      samples in Italian pig herds.
AB  - Gastrointestinal disease is frequent in pigs, and among the different etiological
      agents involved, viruses are considered the leading cause of infection in this
      animal species. Furthermore, about half of the newly identified swine pathogens
      are viruses, many of which may be transmitted to humans by direct contact or by
      indirect transmission pathways. In this study, the prevalence of astrovirus
      (AstV), group A rotavirus (RVA), norovirus (NoV) and hepatitis E virus (HEV)
      infections in pigs was investigated. During 2012-2014, 242 fecal samples were
      collected from pigs at different production stages (5 to 220 days old) on eight
      swine farms located in northern, central and southern Italy. Seven out of eight
      farms analyzed were positive for AstV, which was detected in 163 out of 242
      (67.4%) samples and was the most prevalent virus; 61 of the 163 AstV-positive
      animals (37.4%) had diarrhea. HEV was detected on six farms and in 45 (18.6%) of
      the 242 samples analyzed. Twenty-three HEV-infected pigs had diarrhea (51.1%). A
      lower prevalence was observed for RVA, which was found in 10 of the 242 samples
      (4.1%) from three positive farms, and diarrhea was present only in six infected
      pigs (60.0%). No swine samples were found to be positive for NoV. Genetic
      diversity and phylogenetic relationships of some strains representative of the
      different viruses detected were investigated, confirming a wide heterogeneity of
      viral strains circulating among pigs.

PMID- 26215445
TI  - Molecular characterizations of two grapevine rupestris stem pitting-associated
      virus isolates from China.
AB  - The complete nucleotide sequences of two isolates of grapevine rupestris stem
      pitting-associated virus (LSL and JF) collected from grapevine of Xingcheng in
      Liaoning Province, China, were determined. The genomes of both LSL and JF were
      found to contain five open reading frames (ORFs). Sequence alignments showed that
      the genomic sequences of JF were 76.1 %-83.5 % identical to the other ten GRSPaV
      isolates that have been reported previously and that the nucleotide sequence
      identity of isolate LSL to other isolates was no more than 78 %. Phylogenetic
      analysis based on the complete genome sequence indicated that JF belongs to group
      III and that LSL belongs to a new group (group IV). The average genetic distances
      of the new genetic lineage from groups I, II and III were 0.34, 0.32 and 0.33,
      respectively. 

PMID- 26215444
TI  - Roles of the programmed cell death 1, T cell immunoglobulin mucin-3, and cluster
      of differentiation 288 pathways in the low reactivity of invariant natural killer
      T cells after chronic hepatitis B virus infection.
AB  - One of the main responses of invariant natural killer T (iNKT) cells to antigen
      stimulation is the rapid production of interleukin (IL)-4 and interferon (IFN)
      gamma cytokines. There is a decline in the function of iNKT cells in chronic
      hepatitis B (CHB) patients. In this study, we explored the impact of programmed
      cell death 1 (PD-1), T cell immunoglobulin mucin-3 (Tim-3), and cluster of
      differentiation 28 (CD28) expression on iNKT cell functions in CHB patients. Flow
      cytometry was used to test iNKT frequencies and levels of PD-1, Tim-3, CD28, IL
      4, and IFN-gamma secreted by iNKT cells. An enzyme-linked immunosorbent assay
      (ELISA) was used to measure IL-4 and IFN-gamma secretion upon alpha
      galactosylceramide (alpha-GalCer) activation ex vivo. We found that the levels of
      expression of PD-1 and Tim-3 from iNKT cells in CHB patients were significantly
      higher than in healthy donors (p < 0.05), but there was lower expression of CD28
      (p < 0.05) and an impaired capability to produce IL-4 and IFN-gamma (p < 0.05).
      In vitro alpha-GalCer stimulation upregulated the expression of PD-1(+) iNKT
      cells (p < 0.05), Tim-3(+) iNKT cells (p < 0.05), and CD28(+) iNKT cells (p <
      0.05). In response to combination therapies consisting of alpha-GalCer and anti
      PDL1 monoclonal antibody (mAb) and/or anti-Tim-3 mAbs and/or anti-CD80/anti-CD28
      mAbs, IL-4(+) and IFN-gamma(+) iNKT cells demonstrated different degrees of
      growth (p < 0.05). The functional decline of iNKT cells was closely related to
      the decrease in CD28 expression and the increases of Tim-3 and PD-1. In addition,
      clinical antiviral treatment with lamivudine could partially restore the immune
      function of iNKT cells in CHB patients. 

PMID- 26215446
TI  - Human norovirus genogroup II recombinants in Thailand, 2009-2014.
AB  - Norovirus (NoV) is a major cause of nonbacterial acute gastroenteritis worldwide.
      New strains emerge partly due to viral recombination. In Thailand, there is a
      lack of data on NoV recombinants among clinical isolates. We screened stool
      samples from pediatric diarrheal patients for norovirus by RT-PCR and found GII.4
      to be the most prevalent genotype. Phylogenetic and SimPlot analyses detected
      seven intra-genogroup recombinant strains: three GII.21/GII.3, two GII.12/GII.3,
      and two GII.12/GII.1 recombinants. Maximum chi-square analysis indicated that all
      had similar breakpoints near the ORF1/ORF2 junction (p < 0.001), either slightly
      upstream within the C-terminus of RdRp or downstream within the N-terminal domain
      of VP1. 

PMID- 26215447
TI  - [Detection of alcohol prior to liver transplant, recurrence or continued use?].

PMID- 26215448
TI  - ABX464: a good drug candidate instead of a magic bullet.
AB  - Despite the significant number of antiviral drugs that are currently available in
      the clinics of developed countries, none of these affect the production stage of
      HIV-1 replication, more specifically the process of viral gene expression. For
      instance, several early attempts failed to generate inhibitors of the viral Tat
      protein, the small activator of viral transcription from the long terminal repeat
      (LTR) promoter. A recent study published in Retrovirology by Campos et al.
      presents a new small molecule inhibitor, ABX464, that targets the other small
      viral protein essential for viral gene expression, the Rev protein (Retrovirology
      12:30, 2015). Targeting of multiple virus replication steps and silencing the
      generation of new progeny may be of particular value for current attempts to
      develop novel therapeutic strategies that provide a cure or functional cure for
      HIV-1 infection (Nat Rev Immunol 12: 607-614, 2012). We will briefly review some
      of the unique antiviral properties of ABX464, with the focus on its surprising
      ability to exhibit a sustained antiviral effect in a humanized mouse model.
      Although ABX464 may remain an important new addition to the anti-HIV arsenal, we
      do present a sobering alternative explanation for the long-lasting reduction in
      viral load after treatment cessation.

PMID- 26215449
TI  - Retrospective observational analysis of non-irradiated non-functioning pituitary
      adenomas.
AB  - PURPOSE: The management of choice of non-functioning pituitary adenomas (NFPAs)
      remains debulking surgery when symptomatic. However, patient series
      systematically reporting the NFPAs outcome that were not treated either
      surgically, medically or with radiotherapy during long follow-up thereby giving
      an indication of their natural history are limited. Aim of the present study was
      to evaluate the natural course of presumed NFPAs, the outcome of confirmed NFPAs
      during a long follow-up period. METHODS: Between 1993 and 2013, 84 patients with
      presumed NFPA were studied retrospectively. Patients were enrolled based on the
      following criteria: imaging suggestive of pituitary adenoma, absence of any
      biochemical/clinical evidence of hormonal excess, exclusion of prolactinomas and
      at least one sequential imaging during the follow-up. Repeated assessment of the
      pituitary function, visual fields and imaging was performed at regular intervals.
      The follow-up duration was evaluated from the first and last imaging dates.
      RESULTS: In group F (follow-up without surgery, 33 patients), the macroadenomas
      showed a 15% probability of tumor growth and reduction. Similar tumor size
      alterations were observed also for the microadenomas. In group S (surgery, 51
      patients), both residual tumors (>1 and <1 cm) following initial surgical
      resection remain mainly stable until the last imaging. CONCLUSIONS: Based on the
      given lack of approved medical treatment and the possible risks of surgical
      intervention in presence of significant comorbidities, our study proposes a
      conservative approach with a careful follow-up in patients with NFPAs without
      visual or neurological abnormalities.

PMID- 26215450
TI  - Mitochondrial CB1 receptor is involved in ACEA-induced protective effects on
      neurons and mitochondrial functions.
AB  - Mitochondrial dysfunction contributes to cell death after cerebral
      ischemia/reperfusion (I/R) injury. Cannabinoid CB1 receptor is expressed in
      neuronal mitochondrial membranes (mtCB1R) and involved in regulating
      mitochondrial functions under physiological conditions. However, whether mtCB1R
      affords neuroprotection against I/R injury remains unknown. We used mouse models
      of cerebral I/R, primary cultured hippocampal neurons exposed to oxygen-glucose
      deprivation/reoxygenation (OGD/R) and Ca(2+)-induced injury in purified neuronal
      mitochondria to investigate the role of mtCB1R in neuroprotection. Our results
      showed selective cell-permeant CB1 receptor agonist, arachidonyl-2
      chloroethylamide (ACEA), significantly up-regulated the expression of mtCB1R
      protein in hippocampal neurons and tissue. In vitro, ACEA restored cell
      viability, inhibited generation of reactive oxygen species (ROS), decreased
      lactate dehydrogenase (LDH) release and reduced apoptosis, improved mitochondrial
      function. In vivo, ACEA ameliorated neurological scores, diminished the number of
      TUNEL-positive neurons and decreased the expression of cleaved caspase-3.
      However, ACEA-induced benefits were blocked by the selective cell-permeant CB1
      receptor antagonist AM251, but just partially by the selective cell-impermeant
      CB1 receptor antagonist hemopressin. In purified neuronal mitochondria, mtCB1R
      activation attenuated Ca(2+)-induced mitochondrial injury. In conclusion, mtCB1R
      is involved in ACEA-induced protective effects on neurons and mitochondrial
      functions, suggesting mtCB1R may be a potential novel target for the treatment of
      brain ischemic injury. 

PMID- 26215451
TI  - Rural Patient Access to Primary Percutaneous Coronary Intervention Centers is
      Improved by a Novel Integrated Telemedicine Prehospital System.
AB  - BACKGROUND: As per American Heart Association/American College of Cardiology
      guidelines, the delay between first medical contact and balloon inflation should
      not exceed 90 min for primary percutaneous coronary intervention (PCI). In North
      America, few prehospital systems have been developed to grant rural populations
      timely access to PCI. OBJECTIVES: The objective of the present study was to
      evaluate the ability of an ST-segment elevation myocardial infarction (STEMI)
      system serving suburban and rural populations to achieve the recommended 90-min
      interval benchmark for PCI. METHODS: A prehospital telemedicine program was
      implemented in a rural and suburban region of the Quebec province. Three patient
      groups with STEMI were created according to trajectory: 1) patients already en
      route to a PCI center, 2) patients initially directed to the nearest hospital who
      were subsequently diverted to a PCI center during transport, and 3) patients
      directed to the nearest hospital without transfer for PCI. Time intervals were
      compared across groups. RESULTS: Of the 208 patients diagnosed with STEMI, 14.9%
      were already on their way to a hospital with PCI capabilities, 75.0% were
      rerouted to a PCI center, and 10.1% were directed to the nearest local hospital.
      All patients but one arrived at the PCI center within the 60-min prehospital care
      interval, considering an additional 30 min for balloon inflation at the PCI
      center. CONCLUSION: This study demonstrated that a regionalized prehospital
      system for STEMI patients could achieve the recommended 90-min interval benchmark
      for PCI, while giving timely access to PCI to rural populations that would not
      otherwise have access to this treatment.

PMID- 26215452
TI  - Whipple's disease diagnosed during anti-tumor necrosis factor alpha treatment:
      two case reports and review of the literature.
AB  - INTRODUCTION: Whipple's disease is a rare infectious disease caused by Tropheryma
      whipplei with protean clinical manifestations. This infection may mimic chronic
      inflammatory rheumatisms. CASE PRESENTATION: We report two cases of Whipple's
      disease diagnosed in the context of an inflammatory disease with anti-tumor
      necrosis factor alpha failure. The first patient was a 58-year-old white man with
      psoriatic spondylarthritis, who was treated with adalimumab, etanercept,
      infliximab, tocilizumab and golimumab. The second was a 73-year-old white man
      with rheumatoid arthritis, who received treatment with infliximab, then
      etanercept and rituximab. CONCLUSIONS: Whipple's disease should be suspected in
      all patients diagnosed with chronic inflammatory rheumatism, partially controlled
      or not controlled by treatment with tumor necrosis factor alpha blockers, whose
      condition worsens after treatment.

PMID- 26215453
TI  - Angiotensin II down-regulates natriuretic peptide receptor-A expression and
      guanylyl cyclase activity in H9c2 (2-1) cardiac myoblast cells: Role of ROS and
      NF-kappaB.
AB  - Atrial natriuretic peptide (ANP)/natriuretic peptide receptor-A (NPR-A) system is
      suggested as an endogenous anti-hypertrophic protective mechanism of the heart.
      We have shown previously that Angiotensin II (ANG II), an effector molecule of
      renin-angiotensin-aldosterone system, down-regulates NPR-A expression and its
      activity in vivo rat heart. However, the underlying mechanism by which ANG II
      down-regulates NPR-A expression in the heart is not well understood. Hence, the
      present investigation was aimed to determine whether ANG II-stimulated reactive
      oxygen species (ROS) and NF-kappaB are involved in the down-regulation of NPR-A
      activity in H9c2 (2-1) cardiac myoblast cells. The H9c2 (2-1) cardiac myoblast
      cells were exposed to ANG II (10(-7) M for 20 h) with/or without blocker
      treatment (losartan-10 uM, N-acetyl cysteine (NAC)-10 mM and pyrrolidine
      dithiocarbamate (PDTC)-100 uM). On exposure, ANG II induced a significant
      decrease (P < 0.001) in the expression of Npr1 (coding for NPR-A) gene and NPR-A
      receptor-dependent guanylyl cyclase (GC) activity. The level of expression of
      proto-oncogenes (c-fos, c-myc, and c-jun) and natriuretic peptides (ANP and BNP)
      was increased in ANG II-treated cells when compared with control cells.
      Interestingly, ANG II-dependent repression of Npr1 gene expression and guanylyl
      cyclase (GC) activity was completely restored on treatment with losartan, while
      only a partial reversal was observed in NAC- and PDTC-co-treated cells. In
      conclusion, the results of this study suggest that ROS-mediated NF-kappaB
      activation mechanism is critically involved in the ANG II-mediated down
      regulation of NPR-A expression and its GC activity. 

PMID- 26215455
TI  - The influence of hypermodified nucleosides lysidine and t(6)A to recognize the
      AUA codon instead of AUG: a molecular dynamics simulation study.
AB  - Hypermodified nucleosides lysidine (L) and N(6)-threonylcarbamoyladenosine
      (t(6)A) influence codon-anticodon interactions during the protein biosynthesis
      process. Lysidine prevents the misrecognition of the AUG codon as isoleucine and
      that of AUA as methionine. The structural significance of these modified bases
      has not been studied in detail at the atomic level. Hence, in the present study
      we performed multiple molecular dynamics (MD) simulations of anticodon stem loop
      (ASL) of tRNA(Ile) in the presence and absence of modified bases 'L' and 't(6)A'
      at the 34th and 37th positions respectively along with trinucleotide 'AUA' and
      'AUG' codons. Hydrogen bonding interactions formed by the tautomeric form of
      lysidine may assist in reading the third base adenine of the 'AUA' codon, unlike
      the guanine of the 'AUG' codon. Such interactions might be useful to restrict
      codon specificity to recognize isoleucine tRNA instead of methionine tRNA. The
      t(6)A side chain interacts with the purine ring of the first codon nucleotide
      adenine, which might provide base stacking interactions and could be responsible
      for restricting extended codon-anticodon recognition. We found that ASL tRNA(Ile)
      in the absence of modifications at the 34th and 37th positions cannot establish
      proper hydrogen bonding interactions to recognize the isoleucine codon 'AUA' and
      subsequently disturbs the anticodon loop structure. The binding free energy
      calculations revealed that tRNA(Ile) ASL with modified nucleosides prefers the
      codon AUA over AUG. Thus, these findings might be useful to understand the role
      of modified bases L and t(6)A to recognize the AUA codon instead of AUG. 

PMID- 26215454
TI  - Oleanolic acid alleviated pressure overload-induced cardiac remodeling.
AB  - Previous study has demonstrated that oleanolic acid (OA) possessing the anti
      inflammatory and anti-oxidant properties blunted high-glucose-induced diabetic
      cardiomyopathy and ameliorated experimental autoimmune myocarditis in mice.
      However, little is known about its effects on pressure overload-induced cardiac
      remodeling. Herein, we investigated the effect of OA on cardiac remodeling and
      underlying mechanism. Mice, subjected to aortic banding (AB), were randomly
      assigned into control group and experimental group. OA premixed in diets was
      administered to mice after 3 days of AB. Echocardiography and catheter-based
      measurements of hemodynamic parameters were performed after 8 weeks' treatment of
      OA. Histologic examination and molecular analyses were used to assess cardiac
      hypertrophy and tissue fibrosis. In addition, the inhibitory effects of OA on
      H9c2 cardiomyocytes and cardiac primary fibroblast responded to the stimulation
      of AngII were also investigated. OA ameliorated the systolic and diastolic
      dysfunction induced by pressure overload evidenced by echocardiography and
      catheter-based measurements. OA also decreased the mRNA expression of cardiac
      hypertrophy and fibrosis markers evidenced by RT-PCR. It has been shown in our
      study that pressure overload activated the phosphorylations of Akt, mTOR, p70s6k,
      S6, GSK3beta, and FoxO3a, and treatment of OA attenuated the phosphorylation of
      these proteins. In addition, hypertrophy of cardiomyocytes and fibrosis markers
      induced by AngII was inhibited by OA in vitro. Our findings uncover that OA
      suppressed AB-induced cardiac hypertrophy, partly by inhibiting the activity of
      Akt/mTOR pathway, and suggest that treatment of OA may have a benefit on
      retarding the progress of cardiac remodeling under long terms of pressure
      overload. 

PMID- 26215456
TI  - Synthesis of 3,4,5-Trisubstituted Isoxazoles from Morita-Baylis-Hillman Acetates
      by an NaNO2 /I2 -Mediated Domino Reaction.
AB  - An efficient NaNO2 /I2 -mediated one-pot transformation of Morita-Baylis-Hillman
      (MBH) acetates into alkyl 3-nitro-5-(aryl/alkyl)isoxazole-4-carboxylates is
      described. In a cascade event, initial Michael addition of NaNO2 to the MBH
      acetate furnishes the allylnitro intermediate which undergoes I2 -catalyzed
      oxidative alpha-C?H nitration of the nitromethyl subunit followed by [3+2]
      cycloaddition to afford the title compounds. Structural elaborations of these
      highly substituted isoxazoles by SN Ar reactions and hydrogenolysis allows access
      to useful products. 

PMID- 26215457
TI  - Efficiency of Indigenous Filamentous Fungi for Biodegradation of Petroleum
      Hydrocarbons in Medium and Soil: Laboratory Study from Ecuador.
AB  - The competence of two fungal isolates for degrading petroleum hydrocarbons was
      evaluated. The filamentous fungi were isolated from a crude oil-contaminated soil
      in northeastern Ecuador, and were 99 %-100 % similar in 18S rDNA sequence to the
      genus Geomyces. Their efficiencies of degradation were tested in vitro for 30
      days, using medium and soil microcosm. Residual hydrocarbons were tracked by gas
      liquid chromatography with a flame ionization detector. The maximum removal
      percentages of total petroleum hydrocarbons were 77.3 % and 79.9 % for
      experiments in the medium and soil microcosm, respectively. The percent
      germination of cow pea (Vigna unguiculata) seeds was increased from 20 % to 100 %
      upon bioremediation. Isolates sporulated optimally on minimal salts agar medium
      at pH 5, 25 degrees C temperature, 1 %-1.5 % substrate (crude oil) and 4-6 g L(
      1) N-P-K. These findings suggest that these fungal isolates are potential
      degraders for bioremediation in crude oil-contaminated areas in Ecuador.

PMID- 26215458
TI  - Dustfall Heavy Metal Pollution During Winter in North China.
AB  - In order to study heavy metal pollution in dustfall during Winter in North China,
      forty-four dustfall samples were collected in North China Region from November
      2013 to March 2014. Then forty trace elements content were measured for each
      sample by inductively coupled plasma-mass spectrometry. Finally, the
      contamination characteristics of the main heavy metals were studied through a
      multi-method analysis, including variability analysis, Pearson correlation
      analysis and principal component analysis. Results showed that the relative
      contents of cadmium (Cd), zinc (Zn), copper (Cu), bismuth (Bi), lead (Pb)
      exceeded the standards stipulated in Chinese soil elements background values by
      amazing 4.9 times. In this study, conclusions were drawn that dustfall heavy
      metal pollution in the region was mainly caused by transport pollution,
      metallurgy industrial pollution, coal pollution and steel industrial pollution. 

PMID- 26215459
TI  - Expression Profile of Antioxidant Enzymes in Hemocytes from Freshwater Prawn
      Macrobrachium rosenbergii Exposed to an Elevated Level of Copper.
AB  - This study evaluated the expression level of antioxidant enzymes Cu, Zn
      superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GPx)
      and glutathione S-transferase (GST) in hemocytes of Macrobrachium rosenbergii
      exposed to copper by real-time PCR (qRT-PCR). Results showed that the mRNA
      expression of Cu, Zn-SOD increased to reach a peak at 6 h, then recovered to its
      normal level at 48 h. CAT expression level was significantly increased at 12 h
      and reached a peak at 24 h, but recovered to its normal level later. GPx
      expression level was significantly increased at 6 h and reached the peak at 12 h.
      GST expression level was significantly induced from 12 to 24 h and then dropped
      to its normal level at 48 h. These results indicated that antioxidant enzymes
      were inducible, possibly for removing excessive reactive oxygen species to
      protect prawn from oxidative stress. 

PMID- 26215460
TI  - Copper Uptake Efficiency and Its Distribution Within Bioenergy Grass Giant Reed.
AB  - To evaluate copper uptake and its toxicity on bioenergy grass giant reed (Arundo
      donax L.), experiments were carried out using two epigenetic clonal lines -
      American (BL) and Hungarian (20SZ) ecotypes - grown on elevated Cu concentrations
      up to 26.8 mg L(-1). Neither ecotype showed any noticeable foliar symptoms of Cu
      toxicity at concentrations tested up to 10 mg L(-1). Dry mass of plants of both
      ecotypes significantly increased at the highest Cu treatment compared to control.
      Although the BL ecotype had greater capacity to uptake Cu than 20SZ, the dry mass
      and shoot length of BL was higher than that of 20SZ. Values of bioconcentration
      and transportation factors were higher in the BL than in the 20SZ ecotype. Almost
      45 % of total Cu content within the whole plant was found in the plant root of
      both ecotypes. This demonstrated both ecotypes can be utilized for Cu
      phytoremediation alongside with significant biomass production. 

PMID- 26215461
TI  - Sampling times influence the estimate of parameters in the Weibull dissolution
      model.
AB  - The aim is to determine how well the parameters of the Weibull model of
      dissolution can be estimated in dependency on the chosen times to measure the
      empirical data. The approach is based on the theory of Fisher information. We
      show that in order to obtain the best estimates the data should be collected at
      time instants when tablets actively dissolve or at their close proximity. This is
      in a sharp contrast with commonly used experimental protocols when sampling times
      are distributed rather uniformly. 

PMID- 26215462
TI  - Basal buffer systems for a newly glycosylated recombinant human interferon-beta
      with biophysical stability and DoE approaches.
AB  - The purpose of this study was to develop a basal buffer system for a biobetter
      version of recombinant human interferon-beta 1a (rhIFN-beta 1a), termed R27T, to
      optimize its biophysical stability. The protein was pre-screened in solution as a
      function of pH (2-11) using differential scanning calorimetry (DSC) and dynamic
      light scattering (DLS). According to the result, its experimental pI and optimal
      pH range were 5.8 and 3.6-4.4, respectively. Design of experiment (DoE) approach
      was developed as a practical tool to aid formulation studies as a function of pH
      (2.9-5.7), buffer (phosphate, acetate, citrate, and histidine), and buffer
      concentration (20 mM and 50 mM). This method employed a weight-based procedure to
      interpret complex data sets and to investigate critical key factors representing
      protein stability. The factors used were Tm, enthalpy, and relative helix
      contents which were obtained by DSC and Fourier Transform Infrared spectroscopy
      (FT-IR). Although the weights changed by three responses, objective functions
      from a set of experimental designs based on four buffers were highest in 20 mM
      acetate buffer at pH 3.6 among all 19 scenarios tested. Size exclusion
      chromatography (SEC) was adopted to investigate accelerated storage stability in
      order to optimize the pH value with susceptible stability since the low pH was
      not patient-compliant. Interestingly, relative helix contents and storage
      stability (monomer remaining) increased with pH and was the highest at pH 4.0. On
      the other hand, relative helix contents and thermodynamic stability decreased at
      pH 4.2 and 4.4, suggesting protein aggregation issues. Therefore, the optimized
      basal buffer system for the novel biobetter was proposed to be 20 mM acetate
      buffer at pH 3.8+/-0.2.

PMID- 26215463
TI  - Skin penetration behavior of lipid-core nanocapsules for simultaneous delivery of
      resveratrol and curcumin.
AB  - Polyphenols, which are secondary plant metabolites, gain increasing research
      interest due to their therapeutic potential. Among them, resveratrol and curcumin
      are two agents showing antioxidant, anti-inflammatory, antimicrobial as well as
      anticarcinogenic effects. In addition to their individual therapeutic effect,
      increased activity was reported upon co-delivery of the two compounds. However,
      due to the poor water solubility of resveratrol and curcumin, their clinical
      application is currently limited. In this context, lipid-core nanocapsules (LNC)
      composed of an oily core surrounded by a polymeric shell were introduced as drug
      carrier systems with the potential to overcome this obstacle. Furthermore, the
      encapsulation of polyphenols into LNC can increase their photostability. As the
      attributes of the polyphenols make them excellent candidates for skin treatment,
      the aim of this study was to investigate the effect of co-delivery of resveratrol
      and curcumin by LNC upon topical application on excised human skin. In contrast
      to the formulation with one polyphenol, resveratrol penetrated into deeper skin
      layers when the co-formulation was applied. Based on vibrational spectroscopy
      analysis, these effects are most likely due to interactions of curcumin and the
      stratum corneum, facilitating the skin absorption of the co-administered
      resveratrol. Furthermore, the interaction of LNC with primary human skin cells
      was analyzed encountering a cellular uptake within 24h potentially leading to
      intracellular effects of the polyphenols. Thus, the simultaneous delivery of
      resveratrol and curcumin by LNC provides an intelligent way for immediate and
      sustained polyphenol delivery for skin disease treatment. 

PMID- 26215464
TI  - Influence of coating material on the flowability and dissolution of dry-coated
      fine ibuprofen powders.
AB  - This study investigates the effects of a variety of coating materials on the
      flowability and dissolution of dry-coated cohesive ibuprofen powders, with the
      ultimate aim to use these in oral dosage forms. A mechanofusion approach was
      employed to apply a 1% (w/w) dry coating onto ibuprofen powder with coating
      materials including magnesium stearate (MgSt), L-leucine, sodium stearyl fumarate
      (SSF) and silica-R972. No significant difference in particle size or shape was
      measured following mechanofusion with any material. Powder flow behaviours
      characterised by the Freeman FT4 system indicated coatings of MgSt, L-leucine and
      silica-R972 produced a notable surface modification and substantially improved
      flow compared to the unprocessed and SSF-mechanofused powders. ToF-SIMS provided
      a qualitative measure of coating extent, and indicated a near-complete layer on
      the drug particle surface after dry coating with MgSt or silica-R972. Of
      particular note, the dissolution rates of all mechanofused powders were enhanced
      even with a coating of a highly hydrophobic material such as magnesium stearate.
      This surprising increase in dissolution rate of the mechanofused powders was
      attributed to the lower cohesion and the reduced agglomeration after mechanical
      coating.

PMID- 26215465
TI  - Population data analysis of dissolution time profiles: Assessment of
      physicochemical properties of the drug, drug particles and the pharmaceutical
      formulation.
AB  - Disintegration of finished dosage forms (FDF) and drug dissolution are
      fundamentally important processes that affect bioavailability. Established
      theories do not account for disintegration and usually assume sink conditions for
      drug dissolution that often do not apply. We present the theory to describe the
      disintegration of FDF with subsequent dissolution of liberated particles
      containing the active pharmaceutical ingredient (API) and its application using
      population data analysis. Population modeling, using dissolution profiles of
      400mg cefditoren pivoxil tablets manufactured under various tableting pressures,
      characterized the intrinsic lifetime distribution of the particles and identified
      the presence of crystalline API in the formulation that was proven by X-ray
      diffraction. Modeling further estimated the disintegration time of FDF, the
      solubility of the amorphous API and its chemical instability in the medium that
      were in agreement with the experimentally determined values. This novel approach
      provides a quantitative understanding of the manufacturing process of FDF and can
      substantially contribute to the targeted development of finished dosage forms. 

PMID- 26215466
TI  - Aversive learning shapes neuronal orientation tuning in human visual cortex.
AB  - The responses of sensory cortical neurons are shaped by experience. As a result
      perceptual biases evolve, selectively facilitating the detection and
      identification of sensory events that are relevant for adaptive behaviour. Here
      we examine the involvement of human visual cortex in the formation of learned
      perceptual biases. We use classical aversive conditioning to associate one out of
      a series of oriented gratings with a noxious sound stimulus. After as few as two
      grating-sound pairings, visual cortical responses to the sound-paired grating
      show selective amplification. Furthermore, as learning progresses, responses to
      the orientations with greatest similarity to the sound-paired grating are
      increasingly suppressed, suggesting inhibitory interactions between orientation
      selective neuronal populations. Changes in cortical connectivity between
      occipital and fronto-temporal regions mirror the changes in visuo-cortical
      response amplitudes. These findings suggest that short-term behaviourally driven
      retuning of human visual cortical neurons involves distal top-down projections as
      well as local inhibitory interactions. 

PMID- 26215467
TI  - Effectiveness of Lateral Bone Augmentation on the Alveolar Crest Dimension: A
      Systematic Review and Meta-analysis.
AB  - Lateral ridge augmentation procedures are aimed to reconstruct deficient alveolar
      ridges or to build up peri-implant dehiscence and fenestrations. The objective of
      this systematic review was to assess the efficacy of these interventions by
      analyzing data from 40 clinical studies evaluating bone augmentation through
      either the staged or the simultaneous approach. The PRISMA (Preferred Reporting
      Items for Systematic Reviews and Meta-analyses) guideline for systematic reviews
      was used. The primary outcomes were the changes at reentry, in the ridge width,
      and in the vertical and horizontal dimensions of the peri-implant defect,
      measured in millimeters, in the staged and simultaneous approaches, respectively.
      The results of the meta-analysis showed, for the simultaneous approach, a
      statistically significant defect height reduction when all treatments were
      analyzed together (weighted mean difference [WMD] = -4.28 mm; 95% confidence
      interval: [CI] -4.88, -3.69; P < 0.01). The intervention combining bone
      replacement grafts with barrier membranes was associated with superior outcomes
      The most frequently used intervention was the combination of xenograft and
      bioabsorbable membrane. Similarly, for the staged approach, there was a
      statistically significant horizontal gain when all treatment groups were combined
      (WMD = 3.90 mm; 95% CI: 3.52, 4.28; P < 0.001). The most frequently used
      intervention was the use of autogenous bone blocks. Both treatment strategies led
      to high survival and success rates (>95%) for the implants placed on the
      regenerated sites. Nonexposed sites gained significantly more in the simultaneous
      and staged approaches (WMD = 1.1 and 3.1 mm). 

PMID- 26215468
TI  - Griseofulvin and Fluconazole Reduce Transmission of Tinea Capitis in
      Schoolchildren.
AB  - OBJECTIVE: We evaluated the efficacy of griseofulvin and fluconazole in reducing
      the potential for person-to-person transmission of tinea capitis (TC) in
      children. METHODS: Children with TC with positive fungal cultures were treated
      with griseofulvin 25 mg/kg/day (group A) or fluconazole 6 mg/kg/day (group B) for
      at least 21 days and up to 12 weeks until cure was achieved. Clinical and
      mycologic examinations occurred before treatment and on days 3, 7, 10, 14, and 21
      of treatment. During each visit, mycologic examination was performed from scalp
      lesions of children and fingertips of medical staff and parents after a brief
      touch of the patient's scalp lesions. RESULTS: Ninety patients were enrolled: 48
      treated with griseofulvin and 42 with fluconazole. The predominant species were
      Trichophyton violaceum (n = 44) and Microsporum canis (n = 41), followed by
      Trichophyton mentagrophytes (n = 3) and Trichophyton rubrum (n = 2). Ten days
      after treatment more than 75% of patients from both treatment groups were
      noncontagious. At day 21, all patients from group A were noncontagious and two
      (7%) with positive culture of M. canis from group B were still contagious.
      CONCLUSIONS: No statistically significant differences were found between
      treatment groups. Griseofulvin and fluconazole reduced the potential for disease
      transmission in children with TC, with griseofulvin being more effective for M.
      canis infections, although children with TC may be potentially contagious even
      after up to 3 weeks of treatment. These data should be considered regarding
      school attendance of children with TC.

PMID- 26215469
TI  - Pharmacological approaches in either intermittent or permanent hypoxia: A tale of
      two exposures.
AB  - Hypoxia induces several responses at cardiovascular, pulmonary and reproductive
      levels, which may lead to chronic diseases. This is relevant in human populations
      exposed to high altitude (HA), in either chronic continuous (permanent
      inhabitants) or intermittent fashion (HA workers, tourists and mountaineers). In
      Chile, it is estimated that 1.000.000 people live at highlands and more than
      55.000 work in HA shifts. Initial responses to hypoxia are compensatory and
      induce activation of cardioprotective mechanisms, such as those seen under
      intermittent hypobaric (IH) hypoxia, events that could mediate preconditioning.
      However, whenever hypoxia is prolonged, the chronic activation of cellular
      responses induces long-lasting modifications that may result in acclimatization
      or produce maladaptive changes with increase in cardiovascular risk. HA exposure
      during pregnancy induces hypoxia and oxidative stress, which in turn may promote
      cellular responses and epigenetic modifications resulting in severe impairment in
      growth and development. Sadly, this condition is accompanied with an increased
      fetal and neonatal morbi-mortality. Further, developmental hypoxia may program
      cardio-pulmonary circulations later in postnatal life, ending in vascular
      structural and functional alterations with augmented risk on pulmonary and
      cardiovascular failure. Additionally, permanent HA inhabitants have augmented
      risk and prevalence of chronic hypoxic pulmonary hypertension, right ventricular
      hypertrophy and cardiopulmonary remodeling. Similar responses are seen in adults
      that are intermittently exposed to chronic hypoxia (CH) such as shift workers in
      HA areas. The mechanisms involved determining the immediate, short and long
      lasting effects are still unclear. For several years, the study of the responses
      to hypoxic insults and pharmacological targets has been the motivation of our
      group. This review describes some of the mechanisms underlying hypoxic responses
      and potential therapeutic approaches with antioxidants such as melatonin,
      ascorbate, omega 3 (Omega3) or compounds that increase the nitric oxide (NO)
      bioavailability. 

PMID- 26215471
TI  - Histogram-based normalization technique on human brain magnetic resonance images
      from different acquisitions.
AB  - BACKGROUND: Intensity normalization is an important preprocessing step in brain
      magnetic resonance image (MRI) analysis. During MR image acquisition, different
      scanners or parameters would be used for scanning different subjects or the same
      subject at a different time, which may result in large intensity variations. This
      intensity variation will greatly undermine the performance of subsequent MRI
      processing and population analysis, such as image registration, segmentation, and
      tissue volume measurement. METHODS: In this work, we proposed a new histogram
      normalization method to reduce the intensity variation between MRIs obtained from
      different acquisitions. In our experiment, we scanned each subject twice on two
      different scanners using different imaging parameters. With noise estimation, the
      image with lower noise level was determined and treated as the high-quality
      reference image. Then the histogram of the low-quality image was normalized to
      the histogram of the high-quality image. The normalization algorithm includes two
      main steps: (1) intensity scaling (IS), where, for the high-quality reference
      image, the intensities of the image are first rescaled to a range between the low
      intensity region (LIR) value and the high intensity region (HIR) value; and (2)
      histogram normalization (HN),where the histogram of low-quality image as input
      image is stretched to match the histogram of the reference image, so that the
      intensity range in the normalized image will also lie between LIR and HIR.
      RESULTS: We performed three sets of experiments to evaluate the proposed method,
      i.e., image registration, segmentation, and tissue volume measurement, and
      compared this with the existing intensity normalization method. It is then
      possible to validate that our histogram normalization framework can achieve
      better results in all the experiments. It is also demonstrated that the brain
      template with normalization preprocessing is of higher quality than the template
      with no normalization processing. CONCLUSIONS: We have proposed a histogram-based
      MRI intensity normalization method. The method can normalize scans which were
      acquired on different MRI units. We have validated that the method can greatly
      improve the image analysis performance. Furthermore, it is demonstrated that with
      the help of our normalization method, we can create a higher quality Chinese
      brain template.

PMID- 26215472
TI  - Comparative pathology in bivalves: Aetiological agents and disease processes.
AB  - Comparative pathology as a scientific discipline studies animal diseases in
      relation to their aetiology, pathogenesis and prognosis. Among the main aspects
      of this discipline, regressive changes, host defense responses with pathological
      implications and progressive changes, represent the majority of the possible
      responses of cells and tissues to pathogens and exposure to chemicals. One of the
      most persistent issues in the field of invertebrate pathology is the variability
      in terminology and definition, which has led to confusion in scientific
      communication. The aim of this paper is to provide an overview of the
      pathological basis of bivalve disease (defensive, regressive and progressive
      phenomena) and contribute to the standardised terminology for bivalve molluscan
      disease in the context of comparative pathology. 

PMID- 26215470
TI  - Genomic approaches to identifying targets for treating beta hemoglobinopathies.
AB  - Sickle cell disease and beta thalassemia are common severe diseases with little
      effective pathophysiologically-based treatment. Their phenotypic heterogeneity
      prompted genomic approaches to identify modifiers that ultimately might be
      exploited therapeutically. Fetal hemoglobin (HbF) is the major modulator of the
      phenotype of the beta hemoglobinopathies. HbF inhibits deoxyHbS polymerization
      and in beta thalassemia compensates for the reduction of HbA. The major success
      of genomics has been a better understanding the genetic regulation of HbF by
      identifying the major quantitative trait loci for this trait. If the targets
      identified can lead to means of increasing HbF to therapeutic levels in
      sufficient numbers of sickle or beta-thalassemia erythrocytes, the
      pathophysiology of these diseases would be reversed. The availability of new
      target loci, high-throughput drug screening, and recent advances in genome
      editing provide the opportunity for new approaches to therapeutically increasing
      HbF production. 

PMID- 26215473
TI  - Earlier adolescent substance use onset predicts stronger connectivity between
      reward and cognitive control brain networks.
AB  - BACKGROUND: Early adolescent onset of substance use is a robust predictor of
      future substance use disorders. We examined the relation between age of substance
      use initiation and resting state functional connectivity (RSFC) of the core
      reward processing (nucleus accumbens; NAcc) to cognitive control (prefrontal
      cortex; PFC) brain networks. METHOD: Adolescents in a longitudinal study of
      Mexican-origin youth reported their substance use annually from ages 10 to 16
      years. At age 16, 69 adolescents participated in a resting state functional
      magnetic resonance imaging scan. Seed-based correlational analyses were conducted
      using regions of interest in bilateral NAcc. RESULTS: The earlier that
      adolescents initiated substance use, the stronger the connectivity between
      bilateral NAcc and right dorsolateral PFC, right dorsomedial PFC, right pre
      supplementary motor area, right inferior parietal lobule, and left medial
      temporal gyrus. DISCUSSION: The regions that demonstrated significant positive
      linear relationships between the number of adolescent years using substances and
      connectivity with NAcc are nodes in the right frontoparietal network, which is
      central to cognitive control. The coupling of reward and cognitive control
      networks may be a mechanism through which earlier onset of substance use is
      related to brain function over time, a trajectory that may be implicated in
      subsequent substance use disorders.

PMID- 26215474
TI  - Biological fuel cells: Divergence of opinion.

PMID- 26215476
TI  - A single fluorophore to address multiple logic gates.
AB  - Logic gates with different radixes have been constructed using a biologically
      active molecule, 2-(4'-N,N-dimethylaminophenyl)imidazo[4,5-b]pyridine (DMAPIP-b).
      Taking advantage of the multiple binding sites of the fluorophore, a series of
      different molecular logic gates are developed using fluorescence intensities at
      different wavelengths. The high emission of the molecule is drastically quenched
      in the presence of Fe(3+). It is regained by the addition of an equivalent amount
      of F(-). The fluorescence On-Off nature has been used to construct molecular full
      subtractor and molecular keypad lock system with Boolean logic. A ternary system
      is generated by considering three defined fluorescence intensities at particular
      wavelengths. The smooth dependency of emission intensities with analyte
      concentration is utilized to construct an infinite-valued fuzzy logic system. The
      fuzzy logic system is further coupled with a neuro-adaptation method to predict
      more accurately the dependency of molecular intensity on external inputs. 

PMID- 26215477
TI  - Margaret McCartney: Taking patient safety seriously means minimum staffing
      levels.

PMID- 26215475
TI  - The STIM1-ORAI1 microdomain.
AB  - The regulatory protein STIM1 controls gating of the Ca(2+) channel ORAI1 by a
      direct protein-protein interaction. Because STIM1 is anchored in the ER membrane
      and ORAI1 is in the plasma membrane, the STIM-ORAI pathway can support Ca(2+)
      influx only where the two membranes come into close apposition, effectively
      demarcating a microdomain for Ca(2+) signalling. This review begins with a brief
      summary of the STIM-ORAI pathway of store-operated Ca(2+) influx, then turns to
      the special geometry of the STIM-ORAI microdomain and the expected
      characteristics of the microdomain Ca(2+) signal. A final section of the review
      seeks to place the STIM-ORAI microdomain into a broader context of cellular
      Ca(2+) signalling. 

PMID- 26215478
TI  - Active Smarter Kids (ASK): Rationale and design of a cluster-randomized
      controlled trial investigating the effects of daily physical activity on
      children's academic performance and risk factors for non-communicable diseases.
AB  - BACKGROUND: Evidence is emerging from school-based studies that physical activity
      might favorably affect children's academic performance. However, there is a need
      for high-quality studies to support this. Therefore, the main objective of the
      Active Smarter Kids (ASK) study is to investigate the effect of daily physical
      activity on children's academic performance. Because of the complexity of the
      relation between physical activity and academic performance it is important to
      identify mediating and moderating variables such as cognitive function, fitness,
      adiposity, motor skills and quality of life (QoL). Further, there are global
      concerns regarding the high prevalence of lifestyle-related non-communicable
      diseases (NCDs). The best means to address this challenge could be through
      primary prevention. Physical activity is known to play a key role in preventing a
      host of NCDs. Therefore, we investigated as a secondary objective the effect of
      the intervention on risk factors related to NCDs. The purpose of this paper is to
      describe the design of the ASK study, the ASK intervention as well as the scope
      and details of the methods we adopted to evaluate the effect of the ASK
      intervention on 5 (th) grade children. METHODS & DESIGN: The ASK study is a
      cluster randomized controlled trial that includes 1145 fifth graders (aged 10
      years) from 57 schools (28 intervention schools; 29 control schools) in Sogn and
      Fjordane County, Norway. This represents 95.3 % of total possible recruitment.
      Children in all 57 participating schools took part in a curriculum-prescribed
      physical activity intervention (90 min/week of physical education (PE) and 45
      min/week physical activity, in total; 135 min/week). In addition, children from
      intervention schools also participated in the ASK intervention model (165
      min/week), i.e. a total of 300 min/week of physical activity/PE. The ASK study
      was implemented over 7 months, from November 2014 to June 2015. We assessed
      academic performance in reading, numeracy and English using Norwegian National
      tests delivered by The Norwegian Directorate for Education and Training. We
      assessed physical activity objectively at baseline, midpoint and at the end of
      the intervention. All other variables were measured at baseline and post
      intervention. In addition, we used qualitative methodologies to obtain an in
      depth understanding of children's embodied experiences and pedagogical processes
      taking place during the intervention. DISCUSSION: If successful, ASK could
      provide strong evidence of a relation between physical activity and academic
      performance that could potentially inform the process of learning in elementary
      schools. Schools might also be identified as effective settings for large scale
      public health initiatives for the prevention of NCDs. TRIAL REGISTRATION:
      Clinicaltrials.gov ID nr: NCT02132494 . Date of registration, 6(th) of May, 2014.

PMID- 26215479
TI  - Characteristics of regional cerebral oxygen saturation levels in patients with
      out-of-hospital cardiac arrest with or without return of spontaneous circulation:
      A prospective observational multicentre study.
AB  - AIM: Our study aimed at filling the fundamental knowledge gap on the
      characteristics of regional brain oxygen saturation (rSO2) levels in out-of
      hospital cardiac arrest (OHCA) patients with or without return of spontaneous
      circulation (ROSC) upon arrival at the hospital for estimating the quality of
      cardiopulmonary resuscitation and neurological prognostication in these patients.
      METHODS: We enrolled 1921 OHCA patients from the Japan - Prediction of
      Neurological Outcomes in Patients Post-cardiac Arrest Registry and measured their
      rSO2 immediately upon arrival at the hospital by near-infrared spectroscopy using
      two independent forehead probes (right and left). We also assessed the percentage
      of patients with a good neurological outcome (defined as cerebral performance
      categories 1 or 2) 90 days post cardiac arrest. RESULTS: After 90 days, 79 (4%)
      patients had good neurological outcomes and a median lower rSO2 level of 15% (15
      20%). Compared to patients without ROSC upon arrival at the hospital, those with
      ROSC had significantly higher rSO2 levels (56% [39-65%] vs. 15% [15-17%],
      respectively; P<0.01), and significantly correlated right- and left-sided
      regional brain oxygen saturation levels (R=0.94 vs. 0.66, respectively). In both
      groups, the percentage of patients with a good 90-day neurological outcome
      increased significantly in proportion to their rSO2 levels upon arrival at the
      hospital (P<0.01). CONCLUSION: Our data indicate that measuring rSO2 levels might
      be effective for both monitoring the quality of resuscitation and neurological
      prognostication in patients with OHCA.

PMID- 26215480
TI  - No difference in mortality between men and women after out-of-hospital cardiac
      arrest.
AB  - AIM: Comparing the outcome after out-of-hospital cardiac arrest (OHCA) in men and
      women and to determine whether sex modifies the effect of targeted temperature
      management (TTM) at 33 or 36 degrees C. METHODS: The TTM trial randomized 950
      patients to TTM at 33 or 36 degrees C for 24h. This predefined sub-study of the
      TTM trial assessed survival and neurological outcome defined as Cerebral
      Performance Category (CPC) and modified Rankin Scale (mRS) using female sex as
      main predictor of outcome, in relation to level of TTM and other confounding
      factors. RESULTS: Compared to men, women more often had OHCA at home, p=0.04 and
      less often had bystander defibrillation, p=0.01. No other differences in arrest
      circumstances were found. Coronary angiography (CAG) and percutaneous coronary
      intervention (PCI) <24h after ROSC was less often performed in women, both:
      p=0.02. Female sex was associated with higher mortality in univariate analysis,
      hazard ratio (HR)=1.29, CI=1.04-1.61, p=0.02 compared to men. Adjusting for
      demographic factors (age and comorbidity), arrest circumstances, pre-hospital
      findings, inclusion sites, treatments and status at admission reduced this:
      HR=1.11, CI=0. 87-1.41, p=0.42, and sex was no longer an independent risk factor
      for death. The effect of sex did not modify the effect of TTM at 33 and 36
      degrees C, pinteraction=0.73. CONCLUSION: Female sex seems associated with
      adverse outcome, but this association is largely explained by differences in
      arrest circumstances and in-hospital treatment. Our data shows no interaction
      between sex and the effect of targeting 33 vs. 36 degrees C.

PMID- 26215481
TI  - Cardiac arrest in the workplace and its outcome: a systematic review and meta
      analysis.
AB  - INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) in the workplace appears to
      be managed more effectively than OHCA occurring in other places. A systematic
      review and meta-analysis of the available epidemiological data was performed,
      comparing the rate of survival for OHCA in the workplace, versus survival in
      other locations. METHODS: Four databases (Pub-Med, Scopus, Web of science, "Base
      de Donnees de Sante Publique", BDSP, i.e. the French Public Health Database) were
      searched from 01/2000 to 03/2015, using the key words: ("Cardiac arrest") and
      ("occupational" OR "workplace" OR "public location"). A two stage process with
      two independent readers was used to select relevant papers. Numbers of subjects
      who suffered from OHCA in the workplace versus other locations were extracted
      when possible, as well as their respective outcomes (admitted alive to the
      hospital, discharged alive, good neurological outcome). Metarisks were calculated
      using the generic variance approach (meta-odds ratios metaOR). RESULTS: After
      full-text reading, 17 papers were included, from 9 countries, mostly published
      after 2005, and coming mostly from prospective registers. "Workplace" was defined
      differently in different studies, mostly in terms of industrial sites and
      offices. The workplace was an exceptional location for occurrences of OHCA (from
      0.3% to 4.7% of all OHCA, from 1.3 to 23.8 events per million people per year),
      based on 2077 OHCA. In the quantitative analyses (survival available, 10
      studies), MetaOR were found to be relatively consistent and high (from 1.9 (1.5
      2.3) to 5.9(2.7-13.0)). When OHCA occurring at workplaces were compared to other
      public sites, no significant differences were found. CONCLUSION: There is
      sufficient evidence to support the view that there will be better outcomes for
      OHCA cases that occur in the workplace than for those occurring elsewhere.
      Requirements for occupational health and safety should include prevention of such
      major (albeit rare) events.

PMID- 26215482
TI  - Macromolecular Crowding Modifies the Impact of Specific Hofmeister Ions on the
      Coil-Globule Transition of PNIPAM.
AB  - Macromolecular crowding alters many biological processes ranging from protein
      folding and enzyme reactions in vivo to the precipitation and crystallization of
      proteins in vitro. Herein, we have investigated the effect of specific monovalent
      Hofmeister salts (NaH2PO4, NaF, NaCl, NaClO4, and NaSCN) on the coil-globule
      transition of poly(N-isopropylacrylamide) (PNIPAM) in a crowded macromolecular
      environment as a model for understanding the specific-ion effect on the
      solubility and stability of proteins in a crowded macromolecular environment. It
      was found that although the salts (NaH2PO4, NaF, and NaCl) and the macromolecular
      crowder (polyethylene glycol) lowered the transition temperature almost
      independently, the macromolecular crowder had a great impact on the transition
      temperature in the case of the chaotropes (NaClO4 and NaSCN). The electrostatic
      repulsion between the chaotropic anions (ClO4(-) or SCN(-)) adsorbed on PNIPAM
      may reduce the entropic gain of water associated with the excluded volume effect,
      leading to an increase in the transition temperature, especially in the crowded
      environment. Furthermore, the affinity of the chaotropic anions for PNIPAM
      becomes small in the crowded environment, leading to further modification of the
      transition temperature. Thus, we have revealed that macromolecular crowding
      alters the effect of specific Hofmeister ions on the coil-globule transition of
      PNIPAM. 

PMID- 26215484
TI  - Epicardial Adipose Tissue Thickness, Is It a Reason or a Consequence?

PMID- 26215483
TI  - A national survey on current use of mycophenolate mofetil for childhood-onset
      systemic lupus erythematosus in Japan.
AB  - PURPOSE: To conduct a national survey of systemic lupus erythematosus (SLE)
      patients treated with mycophenolate mofetil (MMF). Based on current information
      on the use of MMF, we aimed to evaluate its efficacy and safety for childhood
      onset (c-) SLE. TARGET: We evaluated 115 patients by questionnaire on MMF use for
      c-SLE in medical facilities specializing in pediatric rheumatic and renal
      diseases. RESULTS: Average age at SLE onset was 10.6 (range, 2-15) years; average
      age at the time of starting MMF was 12.3 (range, 2-15) years. Average dose per
      body surface area was 1,059.3 mg/m(2)/day. Corticosteroid dosing was 20.9 mg/day
      before treatment but 7.7 mg/day after treatment. Laboratory values before and
      after MMF treatment were as follows: C3 increased from 67.0 to 84.9 mg/dl (p <
      0.001), C4 increased from 10.2 to 15.1 mg/dl (p < 0.001), and anti-DNA antibody
      decreased from 154.2 to 18.4 IU/ml (p < 0.001). 24 adverse events in 21 cases
      were reported, but MMF was not discontinued in any. CONCLUSIONS: The amount of
      MMF for c-SLE in Japan is similar to the standard dose in other countries.
      Reduction of corticosteroid dose and improvement of laboratory values represent
      efficacy of MMF. The side effects recorded here indicated tolerability of the
      drug.

PMID- 26215485
TI  - Tuning of temporo-occipital activity by frontal oscillations during virtual
      mirror exposure causes erroneous self-recognition.
AB  - Self-face recognition, a hallmark of self-awareness, depends on 'off-line' stored
      information about one's face and 'on-line' multisensory-motor face-related cues.
      The brain mechanisms of how on-line sensory-motor processes affect off-line
      neural self-face representations are unknown. This study used 3D virtual reality
      to create a 'virtual mirror' in which participants saw an avatar's face moving
      synchronously with their own face movements. Electroencephalographic (EEG)
      analysis during virtual mirror exposure revealed mu oscillations in sensory-motor
      cortex signalling on-line congruency between the avatar's and participants'
      movements. After such exposure and compatible with a change in their off-line
      self-face representation, participants were more prone to recognize the avatar's
      face as their own, and this was also reflected in the activation of face-specific
      regions in the inferotemporal cortex. Further EEG analysis showed that the on
      line sensory-motor effects during virtual mirror exposure caused these off-line
      visual effects, revealing the brain mechanisms that maintain a coherent self
      representation, despite our continuously changing appearance. 

PMID- 26215486
TI  - [Mesenchymal stem cell therapy, a new hope for eye disease].
AB  - Mesenchymal stem cells (MSC) are adult stem cells, first identified in skeletal
      tissues and then found in the entire body. MSC are able to not only differentiate
      into specialized cells within skeletal tissue - chondrocytes, osteocytes,
      adipocytes and fibroblasts - but also secrete a large range of soluble mediators
      defining their secretome and allowing their interaction with a number of cell
      protagonists. Thus, in a general sense, MSC are involved in tissue homeostasis
      through their secretome and are specifically responsible for cell turn-over in
      skeletal tissues. For a decade and a half, safety and efficiency of MSC has led
      to the development of many clinical trials in various fields. However, results
      were often disappointing, probably because of difficulties in methods and
      evaluation. At a time when the first clinical trials using MSC are emerging in
      ophthalmology, the goal of this literature review is to gather and put into
      perspective preclinical and clinical results in order to better predict the
      future of this innovative therapeutic pathway.

PMID- 26215487
TI  - Letter to the Editor.

PMID- 26215488
TI  - Visual Loss After Intraoral Local Anesthesia for the Removal of Circumzygomatic
      and Circum-Mandibular Wires: A Case Report.
AB  - Many types of complications occur after intraoral local anesthesia; however,
      visual loss is a rare one. There have been only a few case reports of visual
      disturbance after intraoral local anesthesia. A 67-year-old man with systemic
      hypertension complained of visual disturbance after a dental local injection for
      circumzygomatic and circum-mandibular wire removal. Forty-nine days later, he had
      partly recovered his vision. To date, the exact mechanism of visual loss after
      dental injection remains unclear. This rare case could provide another clue to
      the etiology and caution against similar complications. 

PMID- 26215489
TI  - Acceleration of Alveolar Ridge Augmentation Using a Low Dose of Recombinant Human
      Bone Morphogenetic Protein-2 Loaded on a Resorbable Bioactive Ceramic.
AB  - PURPOSE: The aim of the present study was to evaluate the effect of a porous
      silica-calcium phosphate composite (SCPC50) loaded with and without recombinant
      human bone morphogenetic protein-2 (rhBMP-2) on alveolar ridge augmentation in
      saddle-type defects. MATERIALS AND METHODS: Micro-granules of SCPC50 resorbable
      bioactive ceramic were coated with rhBMP-2 10 mg and then implanted into a saddle
      type defect (12 * 7 mm) in a dog mandible and covered with a collagen membrane.
      Control groups included defects grafted with SCPC50 granules without rhBMP-2 and
      un-grafted defects. Bone healing was evaluated at 8 and 16 weeks using histologic
      and histomorphometric techniques. The increase in bone height and total defect
      fill were assessed for each specimen using the ImageJ 1.46 program. The release
      kinetics of rhBMP-2 was determined in vitro. The height of the bone in the
      grafted defects and the total defect fill were statistically analyzed. RESULTS:
      SCPC50 enhanced alveolar ridge augmentation as indicated by the increased
      vertical bone height, bone surface area, and bone volume after 16 weeks. SCPC50
      rhBMP-2 provided a sustained release profile of a low effective dose (BMP-2 4.6
      +/- 1.34 pg/mL per hour) during the 1- to 21-day period. The slow rate of release
      of rhBMP-2 from SCPC50 accelerated synchronized complete bone regeneration and
      graft material resorption in 8 weeks. Successful rapid reconstruction of the
      alveolar ridge by SCPC50 and SCPC50-rhBMP-2 occurred without any adverse
      excessive bone formation, inflammation, or fluid-filled voids. CONCLUSIONS:
      Results of this study suggest that SCPC50 is an effective graft material to
      preserve the alveolar ridge after tooth extraction. Coating SCPC50-rhBMP-2
      further accelerated bone regeneration and a considerable increase in vertical
      bone height. These findings make SCPC50 the primary choice as a carrier for rhBMP
      2. SCPC50-rhBMP-2 can serve as an alternative to autologous bone grafting.

PMID- 26215490
TI  - Histopathological Effects of Teriparatide in Medication-Related Osteonecrosis of
      the Jaw: An Animal Study.
AB  - PURPOSE: Osteonecrosis of the jaw after tooth extraction is a major complication
      in patients using bisphosphonates (BPs) for bone lesions, such as for the
      treatment of osteoporosis. The purpose of this study was to investigate the
      histopathologic effects of teriparatide (a synthetic parathyroid hormone) on rats
      developing osteonecrosis with BP use. MATERIALS AND METHODS: Rats (n = 80) that
      had been injected intraperitoneally with zoledronic acid for 7 weeks were used.
      Maxillary first molar extractions and bone defects were established in the same
      region in the eighth week. Teriparatide was administered subcutaneously to
      prevent osteonecrosis. Animals were sacrificed and histopathologic changes were
      examined. Osteoblasts, osteoclasts, inflammatory phase of bone healing, and
      osteonecrotic areas were evaluated. RESULTS: The osteoclast numbers were larger
      in the experimental groups (teriparatide administered before and immediately
      after tooth extraction) than in the control group (administered zoledronic acid).
      The inflammatory phase of bone healing was more pronounced in the experimental
      group (teriparatide administered before tooth extraction) than in the control
      group. There were significant differences in osteoclast numbers and in the
      inflammatory phase of bone healing between the experimental and control groups (P
      < .05). The osteoblast numbers and osteonecrotic areas were similar in size
      between the experimental and control groups. There were no significant
      differences (P > .05). CONCLUSIONS: BPs have negative effects on osteoclasts and
      the inflammatory phase of bone healing, whereas teriparatide was found to be
      effective in eliminating the negative effects of BPs. Teriparatide had positive
      effects in preventing osteonecrosis; therefore, teriparatide could be an
      effective agent for MRONJ.

PMID- 26215491
TI  - Single-Camera Closed-Form Real-Time Needle Tracking for Ultrasound-Guided Needle
      Insertion.
AB  - Many common needle intervention procedures are performed with ultrasound guidance
      because it is a flexible, cost-effective and widely available intra-operative
      imaging modality. In a needle insertion procedure with ultrasound guidance, real
      time calculation and visualization of the needle trajectory can help to guide the
      choice of puncture site and needle angle to reach the target depicted in the
      ultrasound image. We found that it is feasible to calculate the needle trajectory
      with a single camera mounted directly on the ultrasound transducer by using the
      needle markings. Higher accuracy is achieved compared with other similar
      transducer-mounted needle trackers. We used an inexpensive, real-time and easy-to
      use tracking method based on an automatic feature extraction algorithm and a
      closed-form method for pose estimation of the needle. The overall accuracy was
      0.94 +/- 0.46 mm. 

PMID- 26215493
TI  - Ultrasonographic Features of the Major Salivary Glands after Radioactive Iodine
      Ablation in Patients with Papillary Thyroid Carcinoma.
AB  - The aim of this study was to evaluate the ultrasonographic features of the major
      salivary glands (MSGs) after post-operative radioactive iodine ablation (RIA) in
      patients with papillary thyroid carcinoma (PTC). The study population comprised
      202 consecutively registered PTC patients who had undergone total thyroidectomy,
      RIA and follow-up neck ultrasonography. The ultrasonographic features of the MSGs
      in each patient were retrospectively evaluated by a single radiologist, and the
      presence of post-RIA changes was determined by direct comparisons of pre- and
      post-RIA follow-up ultrasonographic scans. Of the 202 patients, 94 (46.5%) had
      post-RIA changes in the MSGs on follow-up ultrasonography. RIA dose was closely
      associated with the prevalence of post-RIA changes. Post-RIA changes were more
      common in the parotid glands (n = 93, 46.0%) than in the submandibular glands (n
      = 7, 3.5%). Common ultrasonographic findings representing post-RIA changes in
      MSGs included coarse echotexture, decreased echogenicity, lobulated margin and
      decreased gland size.

PMID- 26215492
TI  - In Vivo Measures of Shear Wave Speed as a Predictor of Tendon Elasticity and
      Strength.
AB  - The purpose of this study was to assess the potential for ultrasound shear wave
      elastography (SWE) to measure tissue elasticity and ultimate stress in both
      intact and healing tendons. The lateral gastrocnemius (Achilles) tendons of 41
      New Zealand white rabbits were surgically severed and repaired with growth factor
      coated sutures. SWE imaging was used to measure shear wave speed (SWS) in both
      the medial and lateral tendons pre-surgery, and at 2 and 4 wk post-surgery.
      Rabbits were euthanized at 4 wk, and both medial and lateral tendons underwent
      mechanical testing to failure. SWS significantly (p < 0.001) decreased an average
      of 17% between the intact and post-surgical state across all tendons. SWS was
      significantly (p < 0.001) correlated with both the tendon elastic modulus (r =
      0.52) and ultimate stress (r = 0.58). Thus, ultrasound SWE is a potentially
      promising non-invasive technology for quantitatively assessing the mechanical
      integrity of pre-operative and post-operative tendons.

PMID- 26215494
TI  - QSAR studies on 3-(4-biphenylmethyl) 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c]
      Pyridine derivatives as angiotensin II (AT1) receptor antagonist.
AB  - QSAR studies were performed for correlating the chemical composition of 3-(4
      biphenylmethyl) 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridines bearing aryl
      acetic acid esters and acetamides as angiotensin II AT(1) receptor antagonist.
      Four different quantitative structure-property relationship (QSAR) methods namely
      two-dimensional (2D-QSAR), group-based QSAR, k-nearest neighbor and Pharmacophore
      Modeling were employed to obtain statistically significant models. The
      statistically significant best 2D-QSAR model having correlation coefficient r(2)
      = 0:8940 and cross-validated squared correlation coefficient q(2) = 0:7648 with
      external predictive ability of pred_r(2) = 0:8177,pred_r(2)se = 0.4119 and best
      group-based QSAR model having r(2) = 0:7392 and q(2) = 0:6710with pred_r(2) =
      0:7503was developed by SA-principal component regression. The most predictive k
      nearest neighbor model derived from the superposition of conformations has good
      cross-validated q(2) = 0:7637 and satisfied predictive ability r(2)_pred =
      0.7143. Continuing with compounds of substituted 4, 5-dihydro-4-oxo-3H-imidazo
      [4, 5-c] pyridine derivatives chemical feature-based pharmacophore models with
      lowest RMSD value (0.3292 A) consists of two Hac (Hydrogen bond acceptor),
      negative ionizable, and two AroC (Aromatic) features are important for the
      activity. The study suggested that substitution of group at R, R 1, R 2 and Ar,
      and position on 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridine ring with more
      electronegative nature and low bulkiness are favorable for the antihypertensive
      activity. These theoretical results may provide a useful reference for
      understanding the action mechanism and designing potential angiotensin II (AT1)
      receptor antagonist.

PMID- 26215496
TI  - A rare case of neurofibromatosis type I presenting as giant pelvic mass.

PMID- 26215495
TI  - Navigating uncharted territory: a qualitative study of the experience of
      transitioning to wheelchair use among older adults and their care providers.
AB  - BACKGROUND: An increasing number of older adults are procuring a wheelchair for
      mobility; however, the corresponding impact on related injuries, caregiver
      burden, and participation restriction is concerning. To inform the development of
      a wheelchair training program, we pursued a clearer understanding of the
      experience transitioning to wheelchair use for older adult users and their care
      provider. METHODS: Six focus groups were conducted with older experienced
      wheelchair users (n = 10) and care providers (n = 4). Transcripts were analyzed
      using a Conventional Content approach; a coding framework enabled inductive
      theming and summary of the data. RESULTS: Three themes emerged from the user
      group: On My Own reflected both limited training and the necessity of venturing
      out, More Than Meets the Eye addressing barriers to use, and Interdependence
      between wheelchair users and the ambulatory community. Care provider responses
      fell into two themes: the All Encompassing impact of assumed responsibilities and
      Even the Best Laid Plans, where unpredictable and inaccessible environments
      sabotaged participation. CONCLUSIONS: The transition from ambulatory to
      wheelchair mobility can feel like uncharted territory. Balanced support and
      appropriate mentorship are fundamentally important and real-world encounters
      optimize independence and proficiency with skills. The impact on care providers
      is extensive, highlighting the importance of skills training.

PMID- 26215497
TI  - Mature cystic teratoma of the lumbar spine without fat in the cystic cavity.

PMID- 26215498
TI  - Sacral and iliac aneurysmal bone cyst involving the sacroiliac joint.

PMID- 26215499
TI  - Primary intraspinal glioblastoma multiforme in a child.

PMID- 26215500
TI  - Giant immature teratoma.

PMID- 26215501
TI  - Thoracic pneumorachis.

PMID- 26215502
TI  - Mapping a Decade of Physical Activity Interventions for Primary Prevention: A
      Protocol for a Scoping Review of Reviews.
AB  - BACKGROUND: Physical activity is a key behavioral component for the primary
      prevention of noncommunicable disease. The uptake of physical activity is
      influenced by individual and broader factors including social, economic, and
      environmental conditions. OBJECTIVE: The purpose of this paper is to describe a
      protocol for a scoping review of reviews (SRR) that aims to map a decade of
      research focused on physical activity interventions within the domain of primary
      prevention. METHODS: The 5 stages of our SRRs design were adapted from a seminal
      scoping review methodology. Our search strategy was developed for the following
      databases: SPORTDiscus, PubMed, Scopus, the Cochrane Library, the Cumulative
      Index to Nursing and Allied Health Literature, PsycINFO, and Educational
      Resources Information Centre. Two reviewers (LG and AK) independently screened
      eligible studies and compared results to determine the final study selection. One
      reviewer will conduct the data extraction (LG); a second reviewer (AK) will
      assess the results to ensure comprehensiveness and accuracy of the scoping review
      synthesis. RESULTS: The SRRs will provide a broad overview of the physical
      activity research literature specific to primary prevention, and will describe
      key features of physical activity interventions. Potential gaps in the physical
      activity action areas will be identified, and thus, the results will inform
      future research directions. CONCLUSIONS: This paper describes an innovative
      approach for comprehensively mapping an important topic's research trends in the
      last decade.

PMID- 26215503
TI  - Regarding Trauelsen et al. 2015: General versus specific adversity in
      aetiological research into psychosis.

PMID- 26215505
TI  - Cluster analysis differentiates high and low community functioning in
      schizophrenia: Subgroups differ on working memory but not other neurocognitive
      domains.
AB  - BACKGROUND: Schizophrenia is characterized by impairment in multiple aspects of
      community functioning. Available literature suggests that community functioning
      may be enhanced through cognitive remediation, however, evidence is limited
      regarding whether specific neurocognitive domains may be treatment targets. We
      characterized schizophrenia subjects based on their level of community
      functioning through cluster analysis in an effort to identify whether specific
      neurocognitive domains were associated with variation in functioning. METHODS:
      Schizophrenia (SCZ, n=60) and control (CON, n=45) subjects completed a functional
      capacity task, social competence role-play, functional attainment interview, and
      a neuropsychological battery. Multiple cluster analytic techniques were used on
      the measures of functioning in the schizophrenia subjects to generate
      functionally-defined subgroups. MANOVA evaluated between-group differences in
      neurocognition. RESULTS: The cluster analysis revealed two distinct groups,
      consisting of 36 SCZ characterized by high levels of community functioning (HF
      SCZ) and 24 SCZ with low levels of community functioning (LF-SCZ). There was a
      main group effect for neurocognitive performance (p<0.001) with CON outperforming
      both SCZ groups in all neurocognitive domains. Post-hoc tests revealed that HF
      SCZ had higher verbal working memory compared to LF-SCZ (p<=0.05, Cohen's d=0.78)
      but the two groups did not differ in remaining domains. CONCLUSION: The cluster
      analysis classified schizophrenia subjects in HF-SCZ and LF-SCZ using a
      multidimensional assessment of community functioning. Moreover, HF-SCZ
      demonstrated rather preserved verbal working memory relative to LF-SCZ. The
      results suggest that verbal working memory may play a critical role in community
      functioning, and is a potential cognitive treatment target for schizophrenia
      subjects.

PMID- 26215504
TI  - Rare variants in the neurotrophin signaling pathway implicated in schizophrenia
      risk.
AB  - Multiple lines of evidence corroborate impaired signaling pathways as relevant to
      the underpinnings of schizophrenia. There has been an interest in neurotrophins,
      since they are crucial mediators of neurodevelopment and in synaptic connectivity
      in the adult brain. Neurotrophins and their receptors demonstrate aberrant
      expression patterns in cortical areas for schizophrenia cases in comparison to
      control subjects. There is little known about the contribution of neurotrophin
      genes in psychiatric disorders. To begin to address this issue, we conducted high
      coverage targeted exome capture in a subset of neurotrophin genes in 48
      comprehensively characterized cases with schizophrenia-related psychosis. We
      herein report rare missense polymorphisms and novel missense mutations in
      neurotrophin receptor signaling pathway genes. Furthermore, we observed that
      several genes have a higher propensity to harbor missense coding variants than
      others. Based on this initial analysis we suggest that rare variants and missense
      mutations in neurotrophin genes might represent genetic contributions involved
      across psychiatric disorders. 

PMID- 26215506
TI  - Effort-based decision making as an objective paradigm for the assessment of
      motivational deficits in schizophrenia.
AB  - BACKGROUND: Negative symptoms and motivational deficits are prevalent features of
      schizophrenia, and represent robust predictors of real-world functional outcomes.
      The standard for assessment of these symptoms is clinical interview and severity
      ratings on standardized rating scales. In the present study we examined the
      psychometric properties of a performance-based measure of motivational deficits
      in patients with schizophrenia. METHODS: Ninety-seven patients with schizophrenia
      were included in this investigation. Patients' willingness to expend effort for
      reward (i.e., motivation) was evaluated using an effort-based decision making
      paradigm where participants chose over a series of trials whether to expend a
      greater amount of effort for a larger monetary reward versus less effort for a
      smaller reward. Effort performance was evaluated twice, separated by a two-week
      interval. RESULTS: Patients with schizophrenia opted to expend greater effort for
      trials with higher reward value and greater likelihood of reward receipt.
      Patients did not find the task overly difficult and reported being motivated to
      perform well, underscoring the tolerability of the task for patients. Test-retest
      consistency was good and there was only minimal change in scores over time.
      Effort performance was not related to sociodemographic or clinical variables
      (e.g., positive symptoms); however, deficit syndrome patients exerted effort for
      reward at a significantly lower rate than nondeficit patients. CONCLUSIONS: The
      effort-based decision making task used in the present study represents an
      objective paradigm that can be used to evaluate motivational impairments in
      patients with schizophrenia. Such performance-based measures of motivation may
      also serve as viable endpoints in clinical trials.

PMID- 26215507
TI  - Heritability of cortical thickness changes over time in twin pairs discordant for
      schizophrenia.
AB  - BACKGROUND: Cortical thickness and surface area changes have repeatedly been
      found in schizophrenia. Whether progressive loss in cortical thickness and
      surface area are mediated by genetic or disease related factors is unknown. Here
      we investigate to what extent genetic and/or environmental factors contribute to
      the association between change in cortical thickness and surface area and
      liability to develop schizophrenia. METHOD: Longitudinal magnetic resonance
      imaging study over a 5-year interval. Monozygotic (MZ) and dizygotic (DZ) twin
      pairs discordant for schizophrenia were compared with healthy control twin pairs
      using repeated measures analysis of variance (RM-ANOVA) and structural equation
      modeling (SEM). Twins discordant for schizophrenia and healthy control twins were
      recruited from the twin cohort at the University Medical Centre Utrecht, The
      Netherlands. A total of 90 individuals from 46 same sex twin pairs were included:
      9 MZ and 10 DZ discordant for schizophrenia and 14 MZ and 13 (11 complete and 2
      incomplete) DZ healthy twin-pairs. Age varied between 19 and 57years. RESULTS:
      Higher genetic liability for schizophrenia was associated with progressive global
      thinning of the cortex, particularly of the left superior temporal cortex. Higher
      environmental liability for schizophrenia was associated with global attenuated
      thinning of the cortex, and including of the left superior temporal cortex.
      Cortical surface area change was heritable, but not significantly associated with
      higher genetic or environmental liability for schizophrenia. CONCLUSIONS:
      Excessive cortical thinning, particularly of the left superior temporal cortex,
      may represent a genetic risk marker for schizophrenia.

PMID- 26215509
TI  - Chronic kidney disease: ECGs help predict risk of death in CKD.

PMID- 26215508
TI  - Can animal data translate to innovations necessary for a new era of patient
      centred and individualised healthcare? Bias in preclinical animal research.
AB  - BACKGROUND: The public and healthcare workers have a high expectation of animal
      research which they perceive as necessary to predict the safety and efficacy of
      drugs before testing in clinical trials. However, the expectation is not always
      realised and there is evidence that the research often fails to stand up to
      scientific scrutiny and its 'predictive value' is either weak or absent.
      DISCUSSION: Problems with the use of animals as models of humans arise from a
      variety of biases and systemic failures including: 1) bias and poor practice in
      research methodology and data analysis; 2) lack of transparency in scientific
      assessment and regulation of the research; 3) long-term denial of weaknesses in
      cross-species translation; 4) profit-driven motives overriding patient interests;
      5) lack of accountability of expenditure on animal research; 6) reductionist
      materialism in science which tends to dictate scientific inquiry and control the
      direction of funding in biomedical research. Bias in animal research needs to be
      addressed before medical research and healthcare decision-making can be more
      evidence-based. Research funding may be misdirected on studying 'disease
      mechanisms' in animals that cannot be replicated outside tightly controlled
      laboratory conditions, and without sufficient critical evaluation animal research
      may divert attention away from avenues of research that hold promise for human
      health. The potential for harm to patients and trial volunteers from reliance on
      biased animal data(1) requires measures to improve its conduct, regulation and
      analysis. This article draws attention to a few of the many forms of bias in
      animal research that have come to light in the last decade and offers a strategy
      incorporating ten recommendations stated at the end of each section on bias. The
      proposals need development through open debate and subsequent rigorous
      implementation so that reviewers may determine the value of animal research to
      human health. The 10Rs + are protected by a Creative Commons Attribution 3.0
      Unported License and therefore may be 'shared, remixed or built on, even
      commercially, so long as attributed by giving appropriate credit with a link to
      the license, and indicate if changes were made.'

PMID- 26215510
TI  - Chronic kidney disease: Reductions in FGF-23 levels associated with improved
      outcomes.

PMID- 26215511
TI  - Acute kidney injury: Can remote ischaemic preconditioning prevent AKI?

PMID- 26215512
TI  - Management of hypertension in chronic kidney disease.
AB  - Hypertension is a common comorbidity in patients with impaired kidney function.
      The kidney exerts a marked degree of control over blood pressure through various
      mechanisms, such as by regulating sodium balance and hormone secretion through
      the activity of the renin-angiotensin system. The kidney is susceptible to
      injury, and if already damaged can be at risk of further loss of function as a
      consequence of elevated blood pressure. Once elevated blood pressure is
      identified, a combination of sensible lifestyle measures, such as sodium
      restriction and weight loss, with pharmacological intervention to reduce blood
      pressure will usually achieve blood pressure goals. In this Review, we outline
      the importance of blood pressure control for patients with chronic kidney disease
      (CKD), the mechanisms that affect blood pressure control, and the basis for non
      drug and drug therapies. We further discuss the rationale for <140 mmHg systolic
      and <90 mmHg diastolic targets for blood pressure in patients with CKD, with
      consideration for tighter targets in the setting of proteinuria. 

PMID- 26215514
TI  - Renal injury: Prevention of talin-1-mediated activation of neutrophils protects
      against renal ischaemia-reperfusion injury.

PMID- 26215513
TI  - Development and application of human adult stem or progenitor cell organoids.
AB  - Adult stem or progenitor cell organoids are 3D adult-organ-derived epithelial
      structures that contain self-renewing and organ-specific stem or progenitor cells
      as well as differentiated cells. This organoid culture system was first
      established in murine intestine and subsequently developed for several other
      organs and translated to humans. Organoid cultures have proved valuable for basic
      research and for the study of healthy tissue homeostasis and the biology of
      disease. In addition, data from proof-of-principle experiments support promising
      clinical applications of adult stem or progenitor cell organoids. Although renal
      organoids have many potential applications, an adult stem or progenitor cell
      organoid culture system has not yet been developed for the kidney. The
      development of such a system is likely to be challenging because of the intricate
      renal architecture. Differentiated 3D cultures and stem or progenitor cell 3D
      sphere cultures are, however, available for the kidney. These cultures indicate
      the feasibility of renal organoid culture and provide a solid basis for its
      development. In this Review, we discuss the state-of-the-art of human adult stem
      or progenitor cell organoid culture and the potential of renal organoids as tools
      in basic and clinical research. 

PMID- 26215515
TI  - Renal physiology: The proximal tubule and albuminuria-at last a starring role.

PMID- 26215516
TI  - Correction: A ring to rule them all: a cyclic ketene acetal comonomer controls
      the nitroxide-mediated polymerization of methacrylates and confers tunable
      degradability.
AB  - Correction for 'A ring to rule them all: a cyclic ketene acetal comonomer
      controls the nitroxide-mediated polymerization of methacrylates and confers
      tunable degradability' by Vianney Delplace et al., Chem. Commun., 2015, DOI:
      10.1039/c5cc04610f.

PMID- 26215517
TI  - The Effect of C4?H and C5?H on the Microstructure of Aqueous Solutions of 1-Alkyl
      3-methylimidazolium Tetrafluoroborate Ionic Liquids.
AB  - As is well-known, the C2?H proton of 1-ethyl-3-methylimidazolium
      tetrafluoroborate ([Emim]BF4 ) and 1-butyl-3-methylimidazolium tetrafluoroborate
      ([Bmim]BF4 ) has a strong ability to form hydrogen bonds. The purpose of this
      work is to evaluate the effect of the interactions of the C4?H and C5?H protons
      on the microstructure of [Emim]BF4 and [Bmim]BF4 with water by using 1 H NMR
      spectroscopy. The differences between the relative 1 H NMR chemical shifts of
      C2?H, C4?H, and C5?H and between the interaction-energy parameters obtained from
      these chemical shifts are minor, thus suggesting that the interactions of C4?H
      and C5?H may have a considerable effect on the microstructure. To confirm this,
      the viscosities of the systems are estimated by using the interaction-energy
      parameters obtained from the 1 H NMR chemical shifts of the three studied
      aromatic protons and water, showing that the interactions of C4?H and C5?H also
      play an important role in the microstructure.

PMID- 26215518
TI  - Integration of Different Risk Assessment Tools to Improve Stratification of
      Patients with Coronary Artery Disease.
AB  - Cardiovascular disease (CVD) causes unaffordable social and health costs that
      tend to increase as the European population ages. In this context, clinical
      guidelines recommend the use of risk scores to predict the risk of a
      cardiovascular disease event. Some useful tools have been developed to predict
      the risk of occurrence of a cardiovascular disease event (e.g. hospitalization or
      death). However, these tools present some drawbacks. These problems are addressed
      through two methodologies: (i) combination of risk assessment tools: fusion of
      naive Bayes classifiers complemented with a genetic optimization algorithm and
      (ii) personalization of risk assessment: subtractive clustering applied to a
      reduced-dimensional space to create groups of patients. Validation was performed
      based on two ACS-NSTEMI patient data sets. This work improved the performance in
      relation to current risk assessment tools, achieving maximum values of
      sensitivity, specificity, and geometric mean of, respectively, 79.8, 83.8, and
      80.9 %. Additionally, it assured clinical interpretability, ability to
      incorporate of new risk factors, higher capability to deal with missing risk
      factors and avoiding the selection of a standard CVD risk assessment tool to be
      applied in the clinical practice. 

PMID- 26215519
TI  - Robust estimation of the motile cilia beating frequency.
AB  - The estimation of the cilia beating frequency (CBF) is of great interest in
      understanding how the CBF modulates liquid fluxes and how it is controlled by the
      ciliated cell intra- and/or extracellular medium composition in physiological
      processes. Motion artifacts and camera defaults may hinder the computation of the
      frequency variations during long-lasting experiments. We have developed a new
      analysis approach consisting of a preliminary corrective step (removal of a grid
      pattern on the image sequence and shift compensation), followed by a harmonic
      model of the observed cilia using a maximum likelihood estimator framework. It is
      shown that a more accurate estimation of the frequency can be obtained by
      averaging the squared Fourier transform of individual pixels followed by a
      particular summation over the different frequencies, namely the compressed
      spectrum. Robustness of the proposed method over traditional approaches is shown
      by several examples and simulations. The method is then applied to images of
      samples containing ciliated ependymal cells located in the third cerebral
      ventricle of mouse brains, showing that even small variations in CBF in response
      to changes in the amount of oxygenation, pH or glucose were clearly visible in
      the computed frequencies. As a conclusion, this method reveals a fine metabolic
      tuning of the cilia beating in ependimocytes lining the third cerebral ventricle.
      Such regulations are likely to participate in homeostatic mechanisms regulating
      CSF movements and brain energy supply. 

PMID- 26215520
TI  - Extraction of Cole parameters from the electrical bioimpedance spectrum using
      stochastic optimization algorithms.
AB  - Fitting the measured bioimpedance spectroscopy (BIS) data to the Cole model and
      then extracting the Cole parameters is a common practice in BIS applications. The
      extracted Cole parameters then can be analysed as descriptors of tissue
      electrical properties. To have a better evaluation of physiological or
      pathological properties of biological tissue, accurate extraction of Cole
      parameters is of great importance. This paper proposes an improved Cole parameter
      extraction based on bacterial foraging optimization (BFO) algorithm. We employed
      simulated datasets to test the performance of the BFO fitting method regarding
      parameter extraction accuracy and noise sensitivity, and we compared the results
      with those of a least squares (LS) fitting method. The BFO method showed better
      robustness to the noise and higher accuracy in terms of extracted parameters. In
      addition, we applied our method to experimental data where bioimpedance
      measurements were obtained from forearm in three different positions of the arm.
      The goal of the experiment was to explore how robust Cole parameters are in
      classifying position of the arm for different people, and measured at different
      times. The extracted Cole parameters obtained by LS and BFO methods were applied
      to different classifiers. Two other evolutionary algorithms, GA and PSO were also
      used for comparison purpose. We showed that when the classifiers are fed with the
      extracted feature sets by BFO fitting method, higher accuracy is obtained both
      when applying on training data and test data. 

PMID- 26215522
TI  - The Value of Computerized Provider Order Entry: Is It Time for the Debate to Be
      Over?

PMID- 26215523
TI  - Implementing Computerized Provider Order Entry in Acute Care Hospitals in the
      United States Could Generate Substantial Savings to Society.
AB  - BACKGROUND: Computerized provider order entry (CPOE) with clinical decision
      support is a basic criterion for hospitals' meaningful use of electronic health
      record systems. A study was conducted to evaluate from the societal perspective
      the cost-utility of implementing CPOE in acute care hospitals in the United
      States. METHODS: A decision-analytical model compared CPOE with paper ordering
      among patients admitted to acute care hospitals with >25 beds. Parameters
      included start-up and maintenance costs, as well as costs for provider time use,
      medication and laboratory test ordering, and preventable adverse drug events.
      Probabilistic analyses produced incremental costs, effectiveness, and cost
      effectiveness ratios for hospitals in four bed-size categories (25-72, 72-141,
      141-267, 267-2,249). RESULTS: Relative to paper ordering and using typical
      estimates of implementation costs, CPOE had, on average, >99% probability of
      yielding savings to society and improving health. Per hospital in each size
      category, mean life-time savings -in millions-were $11.6 (standard deviation,
      $9.30), $34.4 ($21.2), $71.8 ($43.8), and $170 ($119) (2012 dollars),
      respectively, and quality-adjusted life-years (QALYs) gained were 19.9 (16.9),
      53.7 (38.7), 109 (79.6), and 249 (205). Incremental effectiveness and costs were
      less favorable in certain circumstances, such as high implementation costs.
      Nationwide, anticipated increases in CPOE implementation from 2009 through 2015
      could save $133 billion and 201,000 QALYs. CONCLUSIONS: In addition to improving
      health, implementing CPOE with clinical decision support could yield substantial
      long-term savings to society in the United States, although results for
      individual hospitals are likely to vary.

PMID- 26215524
TI  - Advancing Medication Safety: Establishing a National Action Plan for Adverse Drug
      Event Prevention.
AB  - BACKGROUND: Adverse drug events (ADEs) are important contributors to preventable
      morbidity and mortality, comprising one third of all hospital adverse events. In
      response to growing evidence detailing the high prevalence of ADEs, particularly
      among vulnerable older adults, Congress requested that the Secretary of the
      Department of Health and Human Services (HHS) convene a Federal Interagency
      Steering Committee to establish a National Action Plan to focus on ADE
      prevention. In August 2014, the Office of Disease Prevention and Health Promotion
      released the final version of the National Action Plan for Adverse Drug Event
      Prevention. The Action Plan directly supports the goals of the HHS Strategic Plan
      and the Patient Protection and Affordable Care Act by providing guidance on
      tracking and preventing ADEs, as well as describing evidence-based tools and
      resources to enhance medication safety. ADE ACTION PLAN CONTENT: The Federal
      Interagency Steering Committee focused the Action Plan on ADEs that are
      clinically significant, account for the greatest number of measurable harms as
      identified by using existing surveillance tools, and are largely preventable. As
      such, the decision was made to target three medication classes: anticoagulants,
      diabetes agents (insulin and oral hypoglycemic agents), and opioids. The Action
      Plan is organized around four key areas: surveillance; evidence-based prevention;
      payment, policy incentives, and oversight; and research opportunities to advance
      medication safety. CONCLUSION: One measure of the ADE Action Plan's success will
      be the wider dissemination of information and educational resources to providers
      and patients (or consumers) regarding the risks associated with medications.
      Future Action Plan iterations are likely to consider other high-priority
      medication classes and update the recommendations.

PMID- 26215525
TI  - Facilitation of a Multihospital Community of Practice to Increase Enrollment in
      the Hospital to Home National Quality Improvement Initiative.
AB  - BACKGROUND: Hospital to Home (H2H) is a national quality improvement (QI)
      initiative composed of three recommended hospital interventions to improve the
      transition of care for hospitalized patients with heart disease. A study was
      conducted to determine if enrollment of Department of Veterans Affairs (VA)
      hospitals in H2H and adoption of the recommended interventions would both
      increase following facilitation of an existing Heart Failure (HF) provider-based
      community of practice (COP) within the VA health care system. The VA HF COP
      includes more than 800 VA providers and other VA staff from VA inpatient medical
      centers. METHODS: In 2010, 122 VA hospitals were randomized to facilitation using
      the VA HF COP (intervention) or no facilitation (control). COP members from
      intervention hospitals were invited to periodic teleconferences promoting H2H and
      received multiple e-mails asking members to report interest and then progress in
      H2H implementation. RESULTS: Among the 61 hospitals randomized to HF COP
      facilitation, 33 (54%) enrolled in H2H, compared with 6 (10%) of 61 control
      hospitals (p<.001) at five months after randomization. Of 38 intervention
      hospitals responding to the follow-up survey, 13 stated they had initiated 22 QI
      projects as a result of the H2H campaign. Another 7 hospitals had planned H2H
      projects. Of 20 control hospitals that responded, 5 had initiated 9 projects as a
      result of H2H, and no additional hospitals had plans to do so. CONCLUSIONS:
      Facilitation using the VA HF COP was successful in increasing enrollment in the
      H2H initiative and providing implementation support for recommended QI projects.
      Multihospital provider groups are a potentially valuable tool for implementation
      of national QI campaigns.

PMID- 26215526
TI  - Accuracy of the Adverse Outcome Index: An Obstetrical Quality Measure.
AB  - BACKGROUND: In obstetrics, a nationally accepted set of quality indicators for
      patient safety was not available in the United States until the development of a
      set of 10 adverse outcome measures-the Adverse Outcome Index (AOI). The National
      Perinatal Information Center (NPIC) developed hospital discharge data-based
      algorithms combined with a small set of supplemental patient data for calculation
      of the AOI. A study was conducted to determine the specificity, sensitivity,
      positive predictive value (PPV), and negative predictive value (NPV) of the AOI
      by using the National Perinatal Information Center (NPIC) algorithm. METHODS: A
      retrospective chart review of 4,252 obstetrical and neonatal charts from 2003
      through 2007 was performed. NPIC definitions were compared with the "gold
      standard"-chart review. RESULTS: A total of 229 deliveries among the 4,000
      randomly selected charts had at least one adverse outcome, reflecting an AOI of
      5.7%. For detection of the 10 adverse outcomes within the AOI, the overall
      sensitivity of the AOI was 81.7%, specificity was 98.2%, PPV was 86.3%, and NPV
      was 97.4%. The Kappa value for agreement between the coded charts and the chart
      review was 0.82 (standard deviation=0.01, 95% confidence interval [CI]=0.80
      0.85), which is considered very good. DISCUSSION: The AOI is highly reliant on
      accurate coding and provider documentation and requires validation with manual
      chart review. Concurrent chart review improves the accuracy of the AOI. Caution
      is advised when using the AOI as an exclusive measure of assessing obstetric
      quality because it may be heavily influenced by a single outcome measure;
      perineal laceration rates represented twice the frequency of all other outcomes
      combined. The AOI should be modified to better measure preventable adverse events
      and include a means of accounting for preexisting conditions.

PMID- 26215527
TI  - Connecting Patients and Clinicians: The Anticipated Effects of Open Notes on
      Patient Safety and Quality of Care.

PMID- 26215528
TI  - Loss of DJ-1 elicits retinal abnormalities, visual dysfunction, and increased
      oxidative stress in mice.
AB  - DJ-1/PARK7 mutations or deletions cause autosomal recessive early onset
      Parkinson's disease (PD). Thus, DJ-1 protein has been extensively studied in
      brain and neurons. PD patients display visual symptoms; however, the visual
      symptoms specifically attributed to PD patients carrying DJ-1/PARK7 mutations are
      not known. In this study, we analyzed the structure and physiology of retinas of
      3- and 6-month-old DJ-1 knockout (KO) mice to determine how loss of function of
      DJ-1 specifically contributes to the phenotypes observed in PD patients. As
      compared to controls, the DJ-1 KO mice displayed an increase in the amplitude of
      the scotopic ERG b-wave and cone ERG, while the amplitude of a subset of the dc
      ERG components was decreased. The main structural changes in the DJ-1 KO retinas
      were found in the outer plexiform layer (OPL), photoreceptors and retinal pigment
      epithelium (RPE), which were observed at 3 months and progressively increased at
      6 months. RPE thinning and structural changes within the OPL were observed in the
      retinas in DJ-1 KO mice. DJ-1 KO retinas also exhibited disorganized outer
      segments, central decrease in red/green cone opsin staining, decreased labeling
      of ezrin, broader distribution of ribeye labeling, decreased tyrosine hydroxylase
      in dopaminergic neurons, and increased 7,8-dihydro-8-oxoguanine-labeled DNA
      oxidation. Accelerated outer retinal atrophy was observed in DJ-1 KO mice after
      selective oxidative damage induced by a single tail vein injection of NaIO3,
      exposing increased susceptibility to oxidative stress. Our data indicate that DJ
      1-deficient retinas exhibit signs of morphological abnormalities and
      physiological dysfunction in association with increased oxidative stress.
      Degeneration of RPE cells in association with oxidative stress is a key hallmark
      of age-related macular degeneration (AMD). Therefore, in addition to detailing
      the visual defects that occur as a result of the absence of DJ-1, our data is
      also relevant to AMD pathogenesis. 

PMID- 26215529
TI  - Prevalence of cirrhosis in hepatitis C patients in the Chronic Hepatitis Cohort
      Study (CHeCS): a retrospective and prospective observational study.
AB  - OBJECTIVES: The severity of liver disease in the hepatitis C virus (HCV)-infected
      population in the United States remains uncertain. We estimated the prevalence of
      cirrhosis in adults with chronic hepatitis C (CHC) using multiple parameters
      including liver biopsy, diagnosis/procedure codes, and a biomarker. METHODS:
      Patients enrolled in the Chronic Hepatitis Cohort Study (CHeCS) who received
      health services during 2006-2010 were included. Cirrhosis was identified through
      liver biopsy reports, diagnosis/procedure codes for cirrhosis or hepatic
      decompensation, and Fibrosis-4 (FIB-4) scores >=5.88. Demographic and clinical
      characteristics associated with cirrhosis were identified through multivariable
      logistic modeling. RESULTS: Among 9,783 patients, 2,788 (28.5%) were cirrhotic by
      at least one method. Biopsy identified cirrhosis in only 661 (7%) patients,
      whereas FIB-4 scores and diagnosis/procedure codes for cirrhosis and hepatic
      decompensation identified cirrhosis in 2,194 (22%), 557 (6%), and 482 (5%)
      patients, respectively. Among 661 patients with biopsy-confirmed cirrhosis, only
      356 (54%) had an International Classification of Diseases, Ninth Revision,
      Clinical Modification (ICD-9-CM) code for cirrhosis. Older age, male gender,
      Asian race, Hispanic ethnicity, genotype 3 infection, HIV coinfection, diabetes,
      history of antiviral therapy, and history of alcohol abuse were independently
      associated with higher odds of cirrhosis (all, P<0.05). Conversely, private
      health insurance coverage, black race, and HCV genotype 2 were associated with
      lower odds of cirrhosis. CONCLUSIONS: A high proportion of patients with biopsy
      confirmed cirrhosis are not assigned ICD-9 codes for cirrhosis. Consequently, ICD
      9 codes may not be reliable as the sole indicator of the prevalence of cirrhosis
      in cohort studies. Use of additional parameters suggests a fourfold higher
      prevalence of cirrhosis than is revealed by biopsy alone. These findings suggest
      that cirrhosis in CHC patients may be significantly underdocumented and
      underdiagnosed.

PMID- 26215530
TI  - Treatment of chronic HCV with sofosbuvir and simeprevir in patients with
      cirrhosis and contraindications to interferon and/or ribavirin.
AB  - OBJECTIVES: Patients with chronic hepatitis C virus (HCV) and cirrhosis are in
      critical need of treatment that is both effective and tolerable. The combination
      of simeprevir (SMV), a protease inhibitor, and sofosbuvir (SOF), a polymerase
      inhibitor, without peginterferon and/or ribavirin (PEGINF/RBV) has been shown to
      achieve sustained virologic response (SVR) exceeding 90% in patients with HCV
      genotype 1 with prior nonresponse and/or cirrhosis. The present report describes
      the efficacy of SMV and SOF in patients with cirrhosis, prior or current hepatic
      decompensation, and other contraindications to PEGINF/RBV. METHODS: A total of
      120 consecutive patients with cirrhosis and contraindications to PEGINF/RBV were
      treated with SMV and SOF for 12 weeks. The primary end point was SVR at 12 weeks
      after the completion of treatment. RESULTS: The mean age of the cohort was 60
      years; 63% were male, 48% were Caucasian, 44% were African American, 69% were of
      genotype 1A, 49% were treatment naive, 96% were interleukin-28B non-CC, 33% were
      of Child class B or C, and 25% had prior hepatic decompensation. The SVR by
      intention-to-treat was 81% with a relapse rate of 14%. The SVR by per-protocol
      analysis was 87% with a relapse rate of 13%. The only baseline factor associated
      with SVR by multifactor analysis was Child class. SVR in patients with Child
      class A, B, and C was 87, 77, and 67%, respectively. Eleven percent of the
      patients developed severe adverse events, which included sepsis (two), variceal
      bleeding (two), hepatocellular carcinoma (two), and hyperbilirubinemia (eight).
      One of the patients with sepsis died. Two patients developed relapse more than 12
      weeks after stopping SMV and SOF. CONCLUSIONS: The combination of SMV and SOF
      achieves high rates of SVR in patients with advanced cirrhosis but is lower with
      worsening Child class.

PMID- 26215531
TI  - Detection of Small Bowel Mucosal Healing and Deep Remission in Patients With
      Known Small Bowel Crohn's Disease Using Biomarkers, Capsule Endoscopy, and
      Imaging.
AB  - OBJECTIVES: Mucosal healing (MH) and deep remission (DR) are associated with
      improved outcomes in Crohn's disease (CD). However, most of the current data
      pertain to colonic MH and DR, whereas the evidence regarding the prevalence and
      impact of small bowel (SB) MH is scarce. The aim of this study was to to evaluate
      the prevalence of SBMH and DR in quiescent SBCD. METHODS: Patients with known
      SBCD in clinical remission (CDAI<150) or with mild symptoms (CDAI<220) were
      prospectively recruited and underwent video capsule endoscopy after verification
      of SB patency. Inflammation was quantified using the Lewis score (LS). SBMH was
      defined as LS<135, whereas a significant inflammation was defined as LS>790.
      Clinico-biomarker remission was defined as a combination of clinical remission
      and normal biomarkers. DR was defined as a combination of clinico-biomarker
      remission and MH. RESULTS: Fifty-six patients with proven SB patency were
      enrolled; 52 (92.9%) patients were in clinical remission and 21 (40.4%) in
      clinico-biomarker remission. SBMH was demonstrated in 8/52 (15.4%) of patients in
      clinical remission. Moderate-to-severe SB inflammation was demonstrated in 11/52
      (21.1%) of patients in clinical remission and in 1/21 (4.7%) of patients in
      clinical and biomarker remission. Only 7/52 (13.5%) patients were in DR.
      CONCLUSIONS: SB inflammation is detected in the majority of CD patients in
      clinical and biomarker remission. SBMH and DR were rare and were independent of
      treatment modality. Our findings represent the true inflammatory burden in
      quiescent patients with SBCD.

PMID- 26215532
TI  - Prevalence and Severity of Nonalcoholic Fatty Liver Disease in Non-Obese
      Patients: A Population Study Using Proton-Magnetic Resonance Spectroscopy.
AB  - OBJECTIVES: Some studies suggest that non-obese patients with nonalcoholic fatty
      liver disease (NAFLD) may have more severe disease. We aim to study the
      epidemiology and severity of non-obese NAFLD. METHODS: A total of 911 community
      subjects were randomly recruited from the census database of the Hong Kong
      Government. Intrahepatic triglycerides (IHTG) and liver fibrosis were assessed by
      proton-magnetic resonance spectroscopy and transient elastography, respectively.
      The Asian body mass index cutoff of 25 kg/m(2) was used to define non-obese
      NAFLD. RESULTS: The prevalence of NAFLD was 19.3% in non-obese subjects and 60.5%
      in obese subjects (P<0.001). Compared with obese NAFLD patients, non-obese NAFLD
      patients had similar IHTG content (median 9.8% vs. 9.9%; P=0.100) but lower
      cytokeratin-18 fragments (149 vs. 182 IU/l; P=0.019) and liver stiffness (4.6 vs.
      5.6 kPa; P<0.001). The G allele at the patatin-like phospholipase domain
      containing protein 3 gene (PNPLA3 rs738409) was more common in non-obese than
      obese NAFLD patients (78.4% vs. 59.8%; P=0.001). Obesity, high hemoglobin A1c,
      insulin resistance, hyperferritinemia, and the PNPLA3 G allele were independent
      factors associated with NAFLD in non-obese subjects. Even among non-obese
      subjects with normoglycemia, those with NAFLD were more insulin resistant (mean
      homeostasis model assessment of insulin resistance: 2.0+/-1.0 vs. 1.1+/-1.1;
      P<0.001). CONCLUSIONS: One-fifth of the general non-obese Chinese population has
      NAFLD. Non-obese patients with NAFLD do not have a higher risk of steatohepatitis
      or advanced fibrosis. Patients with risk factors of advanced fibrosis such as
      metabolic syndrome and PNPLA3 G allele carriage should be assessed for severe
      NAFLD.

PMID- 26215534
TI  - Hypertension and its association with anthropometric indexes among pre-university
      students.
AB  - Hypertension has become increasingly common among adolescents. This study aimed
      to investigate the prevalence of hypertension and its association with
      anthropometric indexes among pre-university students. This was a cross-sectional
      study carried out among pre-university students of a public university.
      Anthropometric measurements were conducted using mobile stadiometers, digital
      body fat scales and measuring tapes. Body fat percentage was measured with a body
      composition analyzer, and blood pressure was determined using digital blood
      pressure monitors. Statistical analyses were done using Statistical Package for
      Social Sciences (SPSS) Statistics 20. A total of 218 respondents participated in
      the study. The prevalence of hypertension at risk was 7.3%, which was higher
      among males (16.7%). About 22% of the respondents were overweight and obese. The
      majority of males had a normal waist circumference (WC) (75.9%), but almost half
      of females had a WC value in the unhealthy category (47.0%). Females had higher
      conicity indexes and body fat compared to males. Respondents who were found to
      have hypertension at risk had a higher prevalence of being overweight and having
      unhealthy WC and waist-to-height ratio and had high conicity indexes and a high
      percentage of fat. Risk factors independently associated with hypertension at
      risk included male gender (odds ratio=4.213, 95% CI, 1.238-14.342) and body mass
      index (odds ratio=7.865, 95% CI, 1.165-53.099). Regular screening of hypertension
      at risk among adolescents and initiation of early treatment for those affected
      should be conducted to avoid further complication in later life.

PMID- 26215533
TI  - A TLR9 agonist enhances the anti-tumor immunity of peptide and lipopeptide
      vaccines via different mechanisms.
AB  - The toll-like receptor 9 (TLR9) agonists CpG oligodeoxynucleotides (CpG ODNs)
      have been recognized as promising adjuvants for vaccines against infectious
      diseases and cancer. However, the role of TLR9 signaling in the regulation of
      antigen uptake and presentation is not well understood. Therefore, to investigate
      the effects of TLR9 signaling, this study used synthetic peptides (IDG) and
      lipopeptides (lipoIDG), which are internalized by dendritic cells (DCs) via
      endocytosis-dependent and endocytosis-independent pathways, respectively. Our
      data demonstrated that the internalization of lipoIDG and IDG by bone marrow
      derived dendritic cells (BMDCs) was not enhanced in the presence of CpG ODNs;
      however, CpG ODNs prolonged the co-localization of IDG with CpG ODNs in early
      endosomes. Surprisingly, CpG ODNs enhanced CD8(+) T cell responses, and the anti
      tumor effects of IDG immunization were stronger than those of lipoIDG
      immunization. LipoIDG admixed with CpG ODNs induced low levels of CD8(+) T cells
      and partially inhibit tumor growth. Our findings suggest that CpG ODNs increase
      the retention of antigens in early endosomes, which is important for eliciting
      anti-tumor immunity. These results will facilitate the application of CpG
      adjuvants in the design of different vaccines. 

PMID- 26215535
TI  - Simultaneous Bayesian analysis of contingency tables in genetic association
      studies.
AB  - Genetic association studies lead to simultaneous categorical data analysis. The
      sample for every genetic locus consists of a contingency table containing the
      numbers of observed genotype-phenotype combinations. Under case-control design,
      the row counts of every table are identical and fixed, while column counts are
      random. The aim of the statistical analysis is to test independence of the
      phenotype and the genotype at every locus. We present an objective Bayesian
      methodology for these association tests, which relies on the conjugacy of
      Dirichlet and multinomial distributions. Being based on the likelihood principle,
      the Bayesian tests avoid looping over all tables with given marginals. Making use
      of data generated by The Wellcome Trust Case Control Consortium (WTCCC), we
      illustrate that the ordering of the Bayes factors shows a good agreement with
      that of frequentist p-values. Furthermore, we deal with specifying prior
      probabilities for the validity of the null hypotheses, by taking linkage
      disequilibrium structure into account and exploiting the concept of effective
      numbers of tests. Application of a Bayesian decision theoretic multiple test
      procedure to the WTCCC data illustrates the proposed methodology. Finally, we
      discuss two methods for reconciling frequentist and Bayesian approaches to the
      multiple association test problem. 

PMID- 26215536
TI  - Experimental techniques for screening of antiosteoporotic activity in
      postmenopausal osteoporosis.
AB  - Postmenopausal osteoporosis, a silent epidemic, has become a major health hazard,
      afflicting about 50% of postmenopausal women worldwide and is thought to be a
      disease with one of the highest incidences in senile people. It is a chronic,
      progressive condition associated with micro-architectural deterioration of bone
      tissue that results in low bone mass, decreased bone strength that predisposes to
      an increased risk of fracture. Women are more likely to develop osteoporosis than
      men due to reduction in estrogen during menopause which leads to decline in bone
      formation and increase in bone resorption activity. Estrogen is able to suppress
      the production of proinflammatory cytokines like interleukin (IL)-1, IL-6, IL-7
      and tumor necrosis factor (TNF-alpha). This is why these cytokines are elevated
      in postmenopausal women. In this review article we have made an attempt to
      collate the various methods and parameters most frequently used for screening of
      antiosteoporotic activity in postmenopausal osteoporosis. Pertaining to
      ovariectomized animal model, this is the most appropriate model for studying the
      efficacy of different drugs to prevent bone loss in postmenopausal osteoporosis. 

PMID- 26215537
TI  - Gender and estrous cycle influences on behavioral and neurochemical alterations
      in adult rats neonatally administered ketamine.
AB  - Neonatal N-methyl-D-aspartate (NMDA) receptor blockade in rodents triggers
      schizophrenia (SCZ)-like alterations during adult life. SCZ is influenced by
      gender in age of onset, premorbid functioning, and course. Estrogen, the hormone
      potentially driving the gender differences in SCZ, is known to present
      neuroprotective effects such as regulate oxidative pathways and the expression of
      brain-derived neurotrophic factor (BDNF). Thus, the aim of this study was to
      verify if differences in gender and/or estrous cycle phase during adulthood would
      influence the development of behavioral and neurochemical alterations in animals
      neonatally administered ketamine. The results showed that ketamine-treated male
      (KT-male) and female-in-diestrus (KTF-diestrus, the low estrogen phase) presented
      significant deficits in prepulse inhibition of the startle reflex and spatial
      working memory, two behavioral SCZ endophenotypes. On the contrary, female
      ketamine-treated rats during proestrus (KTF-proestrus, the high estradiol phase)
      had no behavioral alterations. This correlated with an oxidative imbalance in the
      hippocampus (HC) of both male and KTF-diestrus female rats, that is, decreased
      levels of GSH and increased levels of lipid peroxidation and nitrite. Similarly,
      BDNF was decreased in the KTF-diestrus rats while no alterations were observed in
      KTF-proestrus and male animals. The changes in the HC were in contrast to those
      in the prefrontal cortex in which only increased levels of nitrite in all groups
      studied were observed. Thus, there is a gender difference in the adult rat HC in
      response to ketamine neonatal administration, which is based on the estrous
      cycle. This is discussed in relation to neuropsychiatric conditions and in
      particular SCZ.

PMID- 26215538
TI  - An enzootic outbreak of acute disease associated with pathogenic E. coli in Adler
      monkey colony.
AB  - BACKGROUND: In spring 2009 in Adler colony of the Institute of Medical
      Primatology, a large enzootic outbreak of acute intestine infection associated
      with pathogenic E. coli occurred and caused 5% mortality of population (209
      animals). METHODS: The epidemiological analysis, bacteriological investigation,
      postmortem examination, histological analysis, and PCR were used to identify the
      infectious agent. RESULTS: Marked hemorrhagic diathesis, lethargy, dehydration,
      diarrhea with blood, wasting, and sometimes dystrophic changes in articular
      cartilages were noted. Morphologically, hemorrhagic enterocolitis and massive
      hemorrhages were found. PCR investigation of bacteriologically isolated E. coli
      characterized it as enteropathogenic and enteroinvasive E. coli. CONCLUSIONS: The
      outbreak in Adler colony slightly differed from similar outbreak in Florida in
      2014 by more marked hemorrhagic diathesis and articular changes in some monkeys
      caused by polyavitaminosis developed in the course of infection. Sensitive to
      infection were M. mulatta, M. fascicularis, Cercopithecus aethiops, P. hamadryas
      and anubis, and Cebus capucinus.

PMID- 26215539
TI  - Effectiveness and Implications of Alternative Placebo Treatments: A Systematic
      Review and Network Meta-analysis of Osteoarthritis Trials.
AB  - BACKGROUND: Placebo controls are essential in evaluating the effectiveness of
      medical treatments. Although it is unclear whether different placebo
      interventions for osteoarthritis vary in efficacy, systematic differences would
      substantially affect interpretation of the results of placebo-controlled trials.
      OBJECTIVE: To evaluate the effects of alternative placebo types on pain outcomes
      in knee osteoarthritis. DATA SOURCES: MEDLINE, EMBASE, Web of Science, Google
      Scholar, and Cochrane Database from inception through 1 June 2015 and unpublished
      data. STUDY SELECTION: 149 randomized trials of adults with knee osteoarthritis
      that reported pain outcomes and compared widely used pharmaceuticals against
      oral, intra-articular, topical, and oral plus topical placebos. DATA EXTRACTION:
      Study data were independently double-extracted; study quality was assessed by
      using the Cochrane risk of bias tool. DATA SYNTHESIS: Placebo effects that were
      evaluated by using a network meta-analysis with 4 separate placebo nodes
      (differential model) showed that intra-articular placebo (effect size, 0.29 [95%
      credible interval, 0.09 to 0.49]) and topical placebo (effect size, 0.20
      [credible interval, 0.02 to 0.38]) had significantly greater effect sizes than
      did oral placebo. This differential model showed marked differences in the
      relative efficacies and hierarchy of the active treatments compared with a
      network model that considered all placebos equivalent. In the model accounting
      for differential effects, intra-articular and topical therapies were superior to
      oral treatments in reducing pain. When these differential effects were ignored,
      oral nonsteroidal anti-inflammatory drugs were superior. LIMITATIONS: Few studies
      compared different placebos directly. The study could not decisively conclude
      whether disease severity and co-interventions systematically differed between
      trials evaluating different placebos. CONCLUSION: All placebos are not equal, and
      some can trigger clinically relevant responses. Differential placebo effects can
      substantially alter estimates of the relative efficacies of active treatments, an
      important consideration for the design of clinical trials and interpretation of
      their results. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and
      Quality.

PMID- 26215540
TI  - Effect of intraoperative PEEP application on colonic anastomoses healing: An
      experimental animal study.
AB  - PURPOSE: This study aimed to assess the effect of intraoperative PEEP
      intervention on the healing of colonic anastomoses in rabbits. MATERIALS AND
      METHODS: Thirty-two New Zealand type male rabbits were divided into two groups of
      sixteen animals each. Following ventilation with tracheostomy, colonic resection
      and anastomosis were performed in both groups. While 10 cm H2O PEEP level was
      applied in Group I (PEEP), Group II (ZEEP) was ventilated without PEEP throughout
      the surgery. Half of the both PEEP and ZEEP group animals were killed on the
      third postoperative day, while the remaining half on the seventh. Anastomotic
      bursting pressures, the tissue concentrations in hydroxyproline, and histological
      assessments were performed. Besides, intraoperative oxygen saturation and
      postoperative arterial blood gas parameters were also compared. RESULTS: On the
      first postoperative day, both arterial oxygen tension (PO2) and oxygen saturation
      (SO2) in the PEEP group were significantly higher than in the ZEEP group. On the
      seventh postoperative day, the bursting pressures of the anastomoses were
      significantly higher in the PEEP group, however the hydroxyproline content was
      significantly lower in the PEEP group than that in the ZEEP group. At day 7, PEEP
      group was significantly associated with increased neoangiogenesis compared with
      the ZEEP group. CONCLUSION: The anastomotic healing process is positively
      influenced by the intraoperative PEEP application.

PMID- 26215541
TI  - RETRACTED ARTICLE: TN-2 Exerts Anti-Inflammatory Effects on LPS-Induced Rat
      Dorsal Root Ganglion Neurons by Inhibiting TLR4-Mediated NF-kappaB and MAPK
      Pathways.

PMID- 26215543
TI  - A retrospective analysis of environmental risk factors for the diagnosis of deep
      stromal abscess in 390 horses in North Central Florida from 1991 to 2013.
AB  - PURPOSE: The purpose of this investigation was to identify potential
      environmental risk factors for the diagnosis of equine deep stromal abscesses
      (DSA) in the subtropical climate at the University of Florida Veterinary Medical
      Center (UFVMC). METHODS: Cases included were selected from the UFVMC medical
      record and imaging database, and included all cases of equine DSA diagnosed
      during the period from December 1991 to December 2013 in patients residing in
      north central Florida. Patient date of diagnosis and atmospheric data was
      obtained for north central Florida for the corresponding time period. Univariate
      and multivariate general linear models were generated testing effects and
      interactions between environmental conditions. RESULTS: When year, sulfur dioxide
      (SO2 ) and wind were analyzed in the presence of each other, a one-mile per hour
      increase in wind (P = 0.005) significantly increased the number of DSA cases by
      1.63 cases per year. When the influence of temperature was evaluated in
      conjunction with year and nitrogen dioxide (NO2 ), the number of cases decreased
      by 0.1534 per year for every degree increase in temperature ( degrees C) (P =
      0.039). CONCLUSIONS: Wind speed is the first significant atmospheric risk factor
      to be identified for DSA formation in the horse. The importance of environmental
      variance in the incidence of DSA indicates that the pathogenesis of DSA formation
      may be multifactorial, interdependent and provides support in some horses for the
      micropuncture hypothesis of DSA formation related to the involvement of
      environmental conditions causing precorneal tear film and epithelial damage.

PMID- 26215542
TI  - Bioaccessibility and Health Risk Assessment of Cu, Cd, and Zn in "Colored"
      Oysters.
AB  - Bioaccessibility describes the fraction of contaminants released from the food
      matrix into the digestive tracts of humans, which is beneficial for improving the
      health risk assessment of contaminants. In this study, the bioaccessibilities of
      cadmium (Cd), copper (Cu), and zinc (Zn) in two severely contaminated green
      oyster (Crassostrea angulate) and blue oyster (Crassostrea hongkongensis)
      populations were investigated. A human health risk assessment of these metals was
      then performed based on bioaccessibility measurements. Among the three metals,
      the bioaccessibility was the highest for Cu (42-95%), and Cd and Zn had
      comparable bioaccessibility (13-58%). There was no major difference in the
      bioaccessibility between green and blue oysters. A significant correlation
      between the tissue Cu and Zn concentrations was found in these highly
      contaminated oysters. A health risk assessment showed that all three metals in
      both oyster species seriously exceeded the levels recommended by the United
      States Environmental Protection Agency. Thus, oysters from these locations, and
      the metals contained therein, presented quite high risks for human consumption,
      which should be a great cause of concern. A significant relationship was only
      found between metal bioaccessibility and its tissue concentration instead of
      between metal bioaccessibility and subcellular distribution. In addition, a
      significant relationship was only observed between metal health risks and its
      tissue concentration. The influence of metal bioaccessibilities on the health
      risks was limited. This may suggest that in the case of the colored oysters
      examined in this study, metal concentration instead of metal subcellular
      distribution could be the driving factor of the metal bioaccessibility, and metal
      concentration, instead of metal bioaccessibility, could be the driving factor of
      the metal health risks.

PMID- 26215544
TI  - Rural vs. urban disparities in association with lower urinary tract symptoms and
      benign prostatic hyperplasia in ageing men, NHANES 2001-2008.
AB  - OBJECTIVE: The objective of this study was to investigate rural/urban and socio
      demographic disparities in lower urinary tract symptoms and benign prostatic
      hyperplasia (LUTS/BPH) in a nationally representative population of men. METHODS:
      Data on men age >=40 years (N = 4,492) in the 2001-2008 National Health and
      Nutrition Examination Surveys were analysed. Self-report of physician-diagnosed
      enlarged prostate and/or BPH medication use defined recognised LUTS/BPH. Urinary
      symptoms without BPH diagnosis/medications defined unrecognised LUTS/BPH. Rural
      Urban Commuting Area Codes assessed urbanisation. Unadjusted and multivariable
      associations (odds ratios (OR)) between LUTS/BPH and covariates were calculated
      using logistic regression. RESULTS: Recognised and unrecognised LUTS/BPH weighted
      prevalence estimates were 16.5% and 9.6%. There were no significant associations
      between LUTS/BPH and rural/urban status. Significant predisposing factors for
      increased adjusted odds of recognised and unrecognised LUTS/BPH included age,
      hypertension (OR=1.4;1.4), analgesic use (OR=1.4;1.4) and PSA level >4 ng/mL
      (OR=2.3;1.9) when adjusted for rural/urban status, race, education, income,
      alcohol, health insurance, health care and proton pump inhibitor (PPI) use (all p
      <= 0.1). Restricting to urban men only (N = 3,371), healthcare use
      (>=4visits/year) and PPI's increased adjusted odds of recognised LUTS/BPH
      (OR=2.0;1.6); no health insurance and <high school education decreased odds
      (OR=0.5;0.6) after adjusting for variables listed above, antidepressant and
      calcium channel blocker use (p <= 0.1). Also among urban men, adjusted odds of
      unrecognised LUTS/BPH increased for blacks (OR=1.9), Hispanic/Other (OR=1.9) and
      income<$34,999 (OR=1.6). Among rural men only (N = 1,121), adjusted odds of
      recognised and unrecognised LUTS/BPH increased for age, hypertension (OR=1.9;1.7)
      and analgesic use (OR=2.0;1.5) when adjusting for race, CRP, antidepressant and
      dyslipidaemic use (p <= 0.1). CONCLUSION: Rural/urban status was not associated
      with significantly increased adjusted odds of either recognised or unrecognised
      LUTS/BPH.

PMID- 26215545
TI  - Mouse genome annotation by the RefSeq project.
AB  - Complete and accurate annotation of the mouse genome is critical to the
      advancement of research conducted on this important model organism. The National
      Center for Biotechnology Information (NCBI) develops and maintains many useful
      resources to assist the mouse research community. In particular, the reference
      sequence (RefSeq) database provides high-quality annotation of multiple mouse
      genome assemblies using a combinatorial approach that leverages computation,
      manual curation, and collaboration. Implementation of this conservative and
      rigorous approach, which focuses on representation of only full-length and non
      redundant data, produces high-quality annotation products. RefSeq records
      explicitly link sequences to current knowledge in a timely manner, updating
      public records regularly and rapidly in response to nomenclature updates,
      addition of new relevant publications, collaborator discussion, and user
      feedback. Whole genome re-annotation is also conducted at least every 12-18
      months, and often more frequently in response to assembly updates or availability
      of informative data. This article highlights key features and advantages of
      RefSeq genome annotation products and presents an overview of NCBI processes to
      generate these data. Further discussion of NCBI's resources highlights useful
      features and the best methods for accessing our data.

PMID- 26215546
TI  - Best behaviour? Ontologies and the formal description of animal behaviour.
AB  - The development of ontologies for describing animal behaviour has proved to be
      one of the most difficult of all scientific knowledge domains. Ranging from
      neurological processes to human emotions, the range and scope needed for such
      ontologies is highly challenging, but if data integration and computational tools
      such as automated reasoning are to be fully applied in this important area the
      underlying principles of these ontologies need to be better established and
      development needs detailed coordination. Whilst the state of scientific knowledge
      is always paramount in ontology and formal description framework design, this is
      a particular problem with neurobehavioural ontologies where our understanding of
      the relationship between behaviour and its underlying biophysical basis is
      currently in its infancy. In this commentary, we discuss some of the fundamental
      problems in designing and using behaviour ontologies, and present some of the
      best developed tools in this domain. 

PMID- 26215547
TI  - Made to Measure: Designs Tailored to Your Study Needs.
AB  - What is the best study design? Why would we prefer one to another? With many
      different designs, what should we be looking for in our critical reading of the
      literature? We discuss a variety of designs, and their appropriate use. 

PMID- 26215548
TI  - Comparison of Complications for Internal and External Fixation for Charcot
      Reconstruction: A Systematic Review.
AB  - The surgical reconstruction of Charcot deformity can be a challenge for foot and
      ankle surgeons. Consensus is lacking among surgeons regarding the best method of
      surgical fixation to be used in reconstruction, and clear strong evidence is also
      lacking in published studies. We undertook a systematic review of electronic
      databases and other relevant sources in an attempt to better understand the
      complications and outcomes associated with internal and external fixation for
      Charcot foot and ankle reconstruction. A total of 23 level 4 studies with 616
      procedures were identified. Of these, 12 studies with 275 procedures used
      internal fixation, and 11 studies with 341 procedures used external fixation. The
      odds of a successful outcome with internal fixation was 6.86. The odds of a
      successful outcome with external fixation was 13.20 (odds ratio 0.52, 95%
      confidence interval 0.30 to 0.90). The odds of success for internal fixation was
      0.52 times as likely as the odds of success with external fixation. Because the
      odds ratio did not include 1, this difference was statistically significant at
      the p < .05 level. An identified trend was that external fixation was used more
      often in cases deemed to be difficult by the surgeon preoperatively. These
      findings could prove helpful to foot and ankle surgeons when making decisions
      regarding fixation for Charcot reconstruction. 

PMID- 26215549
TI  - Hybrid External Fixation for Arbeitsgemeinschaft fur Osteosynthesefragen (AO) 43
      C Tibial Plafond Fractures.
AB  - Arbeitsgemeinschaft fur Osteosynthesefragen (AO) type 43-C tibial plafond/pilon
      fractures represent a challenge for the treating orthopedic surgeon. We assessed
      the outcomes of using hybrid external fixation for this fracture type. The
      present prospective cohort study was started in August 2009 and ended by July
      2012. Thirty consecutive patients (mean age 37.4 +/- 10.7 years) with a type C
      tibial plafond fracture who had presented to our tertiary care orthopedic
      hospital were included. Motor vehicle accidents and fall from height were the
      cause of the fracture in 14 (46.7%) and 13 (43.3%) patients, respectively. A type
      C3 fracture was present in 25 patients (83.3%), and type C1 and C2 fractures were
      present in 2 (6.7%) and 3 (10.0%) patients, respectively. Nine fractures (30.0%)
      were open. Hybrid external fixation was used for all fractures. All fractures
      were united; clinical healing was achieved by a mean of 18.1 +/- 2.2 weeks
      postoperatively and radiologic healing at a mean of 18.9 +/- 1.9 weeks. The
      fixator was removed at a mean of 20.4 +/- 2.0 weeks postoperatively. At a mean
      follow-up point of 13.4 +/- 2.6 months, the mean modified Mazur ankle score was
      84.6 +/- 10.4. It was not associated with wound classification (p = .256). The
      most commonly seen complication was ankle osteoarthritis (17 patients; 56.7%);
      however, it was mild in >50.0% of the affected patients. In conclusion, using
      hybrid external fixation for type C tibial plafond fractures resulted in good
      outcomes. However, this should be investigated further in studies with a higher
      level of evidence. 

PMID- 26215550
TI  - Posterior Ankle Impingement in Two Athletic Twin Brothers, Could Genetics Play a
      Role?
AB  - Pain posteriorly in the ankle can be caused by bony impingement of the
      posterolateral process of the talus. This process impinges between the tibia and
      calcaneus during deep forced plantar flexion. If this occurs it is called
      posterior ankle impingement syndrome. We report the case of 2 athletic
      monozygotic twin brothers with bony impingement posteriorly in the left ankle.
      Treatment consisted of ankle arthroscopy in both patients during which the
      symptomatic process was easily removed. At 3 months after surgery, both patients
      were completely free of pain, and 1 of the brothers had already returned to
      sports. The posterior ankle impingement syndrome is not a rare syndrome, but it
      has not been described in siblings thus far. That these 2 patients are
      monozygotic twin brothers suggests that genetics could play a role in the
      development of skeletal deformities that can result in posterior ankle
      impingement syndrome. 

PMID- 26215551
TI  - Treatment Outcomes of Corticosteroid Injection and Extracorporeal Shock Wave
      Therapy as Two Primary Therapeutic Methods for Acute Plantar Fasciitis: A
      Prospective Randomized Clinical Trial.
AB  - The outcome of corticosteroid injection (CSI) and extracorporeal shock wave
      therapy (ESWT) as primary treatment of acute plantar fasciitis has been debated.
      The purpose of the present study was to evaluate and compare the therapeutic
      effects of CSI and ESWT in patients with acute (<6-week duration) symptomatic
      plantar fasciitis. Of the 116 eligible patients, 68 were randomized to 2 equal
      groups of 34 patients, each undergoing either ESWT or CSI. The ESWT method
      included 2000 impulses with energy of 0.15 mJ/mm(2) and a total energy flux
      density of 900 mJ/mm(2) for 3 consecutive sessions at 1-week intervals. In the
      CSI group, 40 mg of methyl prednisolone acetate plus 1 mL of lidocaine 2% was
      injected into the maximal tenderness point at the inframedial calcaneal
      tuberosity. The success and recurrence rates and pain intensity measured using
      the visual analog scale, were recorded and compared at the 3-month follow-up
      visit. The pain intensity had reduced significantly in all patients undergoing
      either technique. However, the value and trend of pain reduction in the CSI group
      was significantly greater than those in the ESWT group (p < .0001). In the ESWT
      and CSI groups, 19 (55.9%) and 5 (14.7%) patients experienced treatment failure,
      respectively. Age, gender, body mass index, and recurrence rate were similar
      between the 2 groups (p > .05). Both ESWT and CSI can be used as the primary
      and/or initial treatment option for treating patients with acute plantar
      fasciitis; however, the CSI technique had better therapeutic outcomes. 

PMID- 26215552
TI  - Symptomatic Hardware Removal After First Tarsometatarsal Arthrodesis.
AB  - Severe hallux valgus deformity with proximal instability creates pain and
      deformity in the forefoot. First tarsometatarsal joint arthrodesis is performed
      to reduce the intermetatarsal angle and stabilize the joint. Dorsomedial locking
      plate fixation with adjunctive lag screw fixation is used because of its superior
      construct strength and healing rate. Despite this, questions remain regarding
      whether this hardware is more prominent and more likely to need removal. The
      purpose of the present study was to determine the incidence of symptomatic
      hardware at the first tarsometatarsal joint and to determine the incidence of
      hardware removal resulting from prominence and/or discomfort. A review of 165
      medical records of consecutive patients who had undergone first tarsometatarsal
      joint arthrodesis with plate fixation was conducted. The outcome of interest was
      the incidence of symptomatic hardware removal in patients with clinical union.
      The mean age was 55 (range 18.4 to 78.8) years. The mean follow-up duration was
      65.9 +/- 34.0 (range 7.0 to 369.0) weeks. In our cohort, 25 patients (15.2%) had
      undergone hardware removed because of pain and irritation. Of these patients, 18
      (72.0%) had a locking plate and lag screw removed, and 7 (28.0%) had crossing lag
      screws removed. The fixation of a first tarsometatarsal joint fusion poses a
      difficult situation owing to minimal soft tissue coverage and the inherent need
      for robust fixation to promote fusion. Hardware can become prominent
      postoperatively and can become painful and/or induce cutaneous compromise. The
      results of the present observational investigation imply that surgeons can
      reasonably inform patients that the incidence of symptomatic hardware removal
      after first tarsometatarsal arthrodesis is approximately 15% within a median
      duration of 9.0 months after surgery.

PMID- 26215553
TI  - Late Onset Osteonecrosis of the Proximal Phalanx of the Great Toe in a Child.
AB  - Osteonecrosis, also known as avascular necrosis or osteochondrosis, refers to the
      death of bone tissue resulting from a to lack of blood supply. Osteonecrosis of
      the foot is most commonly seen in the talus and metatarsals and not as frequently
      in other bones. We report an extremely rare case of late-onset osteonecrosis of
      the proximal phalangeal head of the great toe in a 9-year-old male. Plain
      radiographs and computed tomography did not show any findings of osteonecrosis
      initially. However, because of persistent pain at the interphalangeal joint of
      the first toe and a decrease in the range of movement at the interphalangeal
      joint at 7 months after injury, the patient underwent additional examination with
      repeated radiographs and magnetic resonance imaging. We diagnosed late-onset
      osteonecrosis as a result of a subtle traumatic type I dislocation. Conservative
      treatment led to spontaneous recovery, leaving a bony fragment in the
      interphalangeal joint. To our knowledge, this is the first report of late-onset
      proximal phalangeal osteonecrosis after trauma in the great toe. 

PMID- 26215554
TI  - Podiatric Resident Performance on a Basic Competency Examination in
      Musculoskeletal Medicine.
AB  - A basic competency examination in musculoskeletal medicine has previously been
      administered to residents across a variety of medical specialties and has
      demonstrated that medical school preparation in musculoskeletal medicine might be
      inadequate. The objectives of the present study were to assess podiatric surgical
      resident performance on this examination and to assess podiatric surgical
      residency director opinions of the level of importance of the test subject areas.
      A total of 117 podiatric surgical residents from 15 residency programs completed
      the 25-question examination. The residents scored a mean +/- standard deviation
      of 60.32% +/- 12.60% (range 22.00% to 92.00%). On the 7 questions rated by
      podiatric residency directors as >=8 on a 10-point scale of relative importance,
      this score improved to 84.92% +/- 11.93% (range 39.29% to 100.0%). Senior level
      residents did not outperform junior level residents (60.76% versus 60.44%; p =
      .898), and those who had completed a general orthopedics rotation at some point
      in their education did not outperform those who had not (61.12% versus 58.64%; p
      = .370). The podiatric residency directors assigned a mean +/- standard deviation
      importance score of 6.97 +/- 2.07 out of 10 for the 25 questions and suggested a
      mean +/- standard deviation passing score of 69.14% +/- 9.03% for the
      examination. The results of the present investigation provide original data on
      podiatric surgical resident performance on a basic competency examination in
      musculoskeletal medicine. Although the residents scored well for some specific
      test areas, the overall performance was similar to that of previous iterations of
      the examination given to general surgery and internal medicine residents. The
      lower scores compared with those from the orthopedic and physical therapy
      specialties might indicate a need for improved general musculoskeletal medicine
      education within the podiatric curriculum.

PMID- 26215555
TI  - Can Double Osteotomy Be a Solution for Adult Hallux Valgus Deformity With an
      Increased Distal Metatarsal Articular Angle?
AB  - No previous study has reported the results of double metatarsal osteotomy for
      adult hallux valgus deformity with an increased distal metatarsal articular angle
      (DMAA). The purpose of the present study was to evaluate the results after double
      metatarsal osteotomy in adult patients with incongruent hallux valgus deformity.
      We retrospectively reviewed 16 cases of consecutive first metatarsal double
      metatarsal osteotomy without lateral soft tissue release in 14 patients with
      symptomatic hallux valgus associated with an increased DMAA (>=15 degrees  after
      proximal chevron osteotomy on intraoperative radiographs). Clinical results were
      assessed using the American Orthopaedic Foot and Ankle Society scale and the
      visual analog scale. The radiographic results were assessed over time, and
      changes in the DMAA and the relative length of the first metatarsal were assessed
      by measuring each value preoperatively and at the last follow-up visit. The
      American Orthopaedic Foot and Ankle Society and visual analog scale scores were
      significantly improved after surgery. The hallux valgus angle and intermetatarsal
      angle were stabilized >3 months after surgery. The sesamoid position did not
      increase significantly beyond the immediate postoperative period. The mean DMAA
      was corrected from 21.6 degrees  (range 15 degrees  to 29 degrees )
      preoperatively to 11.1 degrees  (range -2 degrees  to 17 degrees ) at the last
      follow-up visit. The mean amount of shortening of the first metatarsal after
      surgery was 5.5 (range 4 to 7) mm. In conclusion, double metatarsal osteotomy
      without lateral soft tissue release in adult hallux valgus deformity results in
      high postoperative recurrence and complication rates.

PMID- 26215556
TI  - Blastomyces Tenosynovitis of the Foot and Ankle: A Case Report and Review of the
      Literature.
AB  - Deep fungal infection localized to the foot is not common, and when it occurs it
      often affects immunocompromised individuals. In this report, we describe the case
      of an adult diabetic patient who suffered with with Blastomycosis infection of
      the flexor digitorum longus and peroneal tendon sheaths. The condition was
      treated with systemic antifungal therapy and surgical debridement. 

PMID- 26215557
TI  - Interventions to facilitate recovering from job stress in an oncology setting:
      One size does not fit all.

PMID- 26215559
TI  - Correlation of tumor-infiltrating lymphocytes with bladder cancer recurrence in
      patients with solitary low-grade urothelial carcinoma.
AB  - The aim of the present study was to correlate tumor-infiltrating lymphocytes
      (TIL) with bladder cancer recurrence in patients with solitary low-grade non
      muscle-invasive bladder cancer (NMIBC). We retrospectively identified from the
      institutional database 115 patients with solitary low-grade NMIBC after
      transurethral resection (TURBT) without adjuvant therapy and with complete follow
      up, between 1996 and 2006. Tumor specimens were retrieved and tissue microarrays
      were constructed. Patients were divided in two groups: those who developed
      recurrent disease (n = 69) and those without recurrence (n = 46) during a follow
      up period of a minimum of 5 years. Immunohistochemical staining for TIL with anti
      CD3, CD4, CD8, CD20, CD56, CD68, and granzyme B (GrB) was performed. Student's t
      test, Mann-Whitney U test, as well as uni- and multivariate analyses were applied
      to compare the two patient groups. TIL were predominantly observed in cancer
      stroma. The number of CD3+ and CD8+ lymphocytes observed in the non-recurrent
      group of patients was lower than that in recurrent patients (p = 0.0001, p =
      0.0002, respectively). Also, in uni- and multivariate analyses, levels of CD3+
      TIL (OR = 5.4035; p = 0.0001 and OR = 5.8280; p = 0.0102) and CD8+ TIL (OR =
      3.2857; p = 0.0036 and OR = 5.3257; p = 0.0092) showed prognostic value with
      regard to NMIBC recurrence. Our results suggest that CD3+ and CD8+ TIL are
      predictive of bladder cancer recurrence in patients with solitary low-grade NMIBC
      which might facilitate identification of patients with higher risk of recurrence.
      However, prospective validating studies have to confirm these results before
      immunohistochemical staining for CD3 and CD8 TIL can be included in the clinical
      workup of these patients.

PMID- 26215560
TI  - Discerning the healing path--how nurses assist patient spirituality in diverse
      health care settings.
AB  - AIMS AND OBJECTIVES: To examine nurses' experiences in spiritual care in diverse
      clinical settings, preferably not palliative care. BACKGROUND: Spirituality is
      part of holistic nursing care. The concept of spiritual literacy is introduced as
      the nurse's ability to read the spiritual signs of the human experience. DESIGN:
      Classical grounded theory methodology with open and selective coding was used to
      identify the participants' main concern and the strategies they used to resolve
      it, and to develop a substantive grounded theory. METHOD: Data were collected in
      2008 and 2014 during eight focus group interviews with a total of 22 nurses
      recruited from a master's programme, postgraduate programmes and a local
      hospital. Data were analysed through constant comparison until the grounded
      theory emerged. RESULTS: The participants' main concern was how to assist the
      patient to alleviation. The participants resolved this by Discerning the healing
      path, which comprises three stages: Tuning in on spirituality, Uncovering deep
      concerns and Facilitating the healing process. These three stages are accompanied
      all the way by the participants' Willingness to overcome own comfort zone and
      Building a trusting relationship. CONCLUSION: Spirituality is of relevance for
      all areas of nursing care, not just dying patients or those in palliative care.
      Spirituality relates to the deep and important things in life and affects how
      patients face health issues. Nurses attend to spirituality in patients because
      the pain of the soul touches them and the calmness of spiritual peace amazes
      them. RELEVANCE TO CLINICAL PRACTICE: The professional culture in the health care
      team socialises nurses into the workplace, and leaders need to pay close
      attention to how they can foster openness to spiritual matters. The personal and
      professional maturity of the nurse is fundamental to his or her willingness and
      ability to overcome own comfort zone.

PMID- 26215562
TI  - Special issue in computational modeling on biological systems.

PMID- 26215563
TI  - Term abdominal pregnancy: a case report.
AB  - INTRODUCTION: Abdominal pregnancy is a rare form of ectopic pregnancy with very
      high maternal and fetal morbidity and mortality. A high index of suspicion is
      crucial for prompt diagnosis and management especially in low-resource countries.
      CASE PRESENTATION: A 32-year-old gravida III para II Amhara woman presented with
      shortness of breath and progressive abdominal distension and pain. An emergency
      laparotomy was performed with the impression of abdominal pregnancy.
      Intraoperatively, the fetus was seen in an intact amniotic sac in her abdomen,
      her uterus was ruptured at the fundus and the placenta was extensively adhered to
      the edge of the ruptured site. The patient and neonate progressed well and were
      discharged. CONCLUSIONS: Term abdominal pregnancy is an extremely rare diagnosis
      and requires a high index of suspicion. The life-threatening complication is
      bleeding from the detached placental site. A thorough examination of the newborn
      is important to rule out congenital anomalies.

PMID- 26215561
TI  - Molecular mechanisms of gravity perception and signal transduction in plants.
AB  - Gravity is one of the environmental cues that direct plant growth and
      development. Recent investigations of different gravity signalling pathways have
      added complexity to how we think gravity is perceived. Particular cells within
      specific organs or tissues perceive gravity stimulus. Many downstream signalling
      events transmit the perceived information into subcellular, biochemical, and
      genomic responses. They are rapid, non-genomic, regulatory, and cell-specific.
      The chain of events may pass by signalling lipids, the cytoskeleton,
      intracellular calcium levels, protein phosphorylation-dependent pathways,
      proteome changes, membrane transport, vacuolar biogenesis mechanisms, or nuclear
      events. These events culminate in changes in gene expression and auxin lateral
      redistribution in gravity response sites. The possible integration of these
      signalling events with amyloplast movements or with other perception mechanisms
      is discussed. Further investigation is needed to understand how plants coordinate
      mechanisms and signals to sense this important physical factor. 

PMID- 26215565
TI  - XXXIVth Seminar of the French-Speaking Society for Theoretical Biology: Saint
      Flour (Cantal), France, 26-28 May, 2014.

PMID- 26215564
TI  - HIV-1 Vpu utilizes both cullin-RING ligase (CRL) dependent and independent
      mechanisms to downmodulate host proteins.
AB  - BACKGROUND: Hijacking of the cullin-RING E3 ubiquitin ligase (CRL) machinery is a
      common mechanism employed by diverse groups of viruses for the efficient
      counteraction and degradation of host proteins. In particular, HIV-1 Vpu usurps
      the SCF(beta-TrCP) E3 ubiquitin ligase complex to mark CD4 for degradation by the
      26S proteasome. Vpu also interacts with and downmodulates a number of other host
      proteins, including the restriction factor BST-2. However, whether Vpu primarily
      relies on a cullin-dependent or -independent mechanism to antagonize its cellular
      targets has not been fully elucidated. RESULTS: We utilized a sulphamate AMP
      analog, MLN4924, to effectively block the activation of CRLs within infected
      primary CD4(+) T cells. MLN4924 treatment, in a dose dependent manner,
      efficiently relieved surface downmodulation and degradation of CD4 by NL4-3 Vpu.
      MLN4924 inhibition was highly specific, as this inhibitor had no effect on Nef's
      ability to downregulate CD4, which is accomplished by a CRL-independent
      mechanism. In contrast, NL4-3 Vpu's capacity to downregulate BST-2, NTB-A and
      CCR7 was not inhibited by the drug. Vpu's from both a transmitted founder (T/F)
      and chronic carrier (CC) virus preserved the ability to downregulate BST-2 in the
      presence of MLN4924. Finally, depletion of cellular pools of cullin 1 attenuated
      Vpu's ability to decrease CD4 but not BST-2 surface levels. CONCLUSIONS: We
      conclude that Vpu employs both CRL-dependent and CRL-independent modes of action
      against host proteins. Notably, we also establish that Vpu-mediated reduction of
      BST-2 from the cell surface is independent of beta-TrCP and the CRL- machinery
      and this function is conserved by Vpu's from primary isolates. Therefore,
      potential therapies aimed at antagonizing the activities of Vpu may need to
      address these distinct mechanisms of action in order to achieve a maximal effect.

PMID- 26215566
TI  - miR-431 promotes differentiation and regeneration of old skeletal muscle by
      targeting Smad4.
AB  - The myogenic capacity of myoblasts decreases in skeletal muscle with age. In
      addition to environmental factors, intrinsic factors are important for
      maintaining the regenerative potential of muscle progenitor cells, but their
      identities are largely unknown. Here, comparative analysis of microRNA (miRNA)
      expression profiles in young and old myoblasts uncovered miR-431 as a novel miRNA
      showing markedly reduced abundance in aged myoblasts. Importantly, elevating miR
      431 improved the myogenic capacity of old myoblasts, while inhibiting endogenous
      miR-431 lowered myogenesis. Bioinformatic and biochemical analyses revealed that
      miR-431 directly interacted with the 3' untranslated region (UTR) of Smad4 mRNA,
      which encodes one of the downstream effectors of TGF-beta signaling. In keeping
      with the low levels of miR-431 in old myoblasts, SMAD4 levels increased in this
      myoblast population. Interestingly, in an in vivo model of muscle regeneration
      following cardiotoxin injury, ectopic miR-431 injection greatly improved muscle
      regeneration and reduced SMAD4 levels. Consistent with the finding that the mouse
      miR-431 seed sequence in the Smad4 3' UTR is conserved in the human SMAD4 3' UTR,
      inhibition of miR-431 also repressed the myogenic capacity of human skeletal
      myoblasts. Taken together, our results suggest that the age-associated miR-431
      plays a key role in maintaining the myogenic ability of skeletal muscle with age.

PMID- 26215567
TI  - A novel 3' splice site recognition by the two zinc fingers in the U2AF small
      subunit.
AB  - The pre-mRNA splicing reaction of eukaryotic cells has to be carried out
      extremely accurately, as failure to recognize the splice sites correctly causes
      serious disease. The small subunit of the U2AF heterodimer is essential for the
      determination of 3' splice sites in pre-mRNA splicing, and several single-residue
      mutations of the U2AF small subunit cause severe disorders such as
      myelodysplastic syndromes. However, the mechanism of RNA recognition is poorly
      understood. Here we solved the crystal structure of the U2AF small subunit
      (U2AF23) from fission yeast, consisting of an RNA recognition motif (RRM) domain
      flanked by two conserved CCCH-type zinc fingers (ZFs). The two ZFs are positioned
      side by side on the beta sheet of the RRM domain. Further mutational analysis
      revealed that the ZFs bind cooperatively to the target RNA sequence, but the RRM
      domain acts simply as a scaffold to organize the ZFs and does not itself contact
      the RNA directly. This completely novel and unexpected mode of RNA-binding
      mechanism by the U2AF small subunit sheds light on splicing errors caused by
      mutations of this highly conserved protein. 

PMID- 26215569
TI  - High Performance Polymer Nanowire Field-Effect Transistors with Distinct
      Molecular Orientations.
AB  - Polymer nanowires based on two diketopyrrolopyrrole conjugated polymers with
      similar chemical structures are shown to have distinct "edge-on" and "face-on"
      configurations in addition to high well-balanced hole and electron mobilities of
      5.47 and 5.33 cm(2) V(-1) s(-1) in field-effect transistors. 

PMID- 26215570
TI  - Gastrointestinal Metastases from Breast Cancer, a Comprehensive Review.

PMID- 26215571
TI  - Computer use in primary care and patient-physician communication.
AB  - OBJECTIVES: This study evaluated how physicians and patients perceive the impact
      of computer use on clinical communication, and how a patient-centered orientation
      can influence this impact. METHODS: The study followed a descriptive cross
      sectional design and included 106 family physicians and 392 patients. An original
      questionnaire assessed computer use, participants' perspective of its impact, and
      patient centered strategies. RESULTS: Physicians reported spending 42% of
      consultation time in contact with the computer. A negative impact of computer in
      patient-physician communication regarding the consultation length,
      confidentiality, maintaining eye contact, active listening to the patient, and
      ability to understand the patient was reported by physicians, while patients
      reported a positive effect for all the items. Physicians considered that the
      usual computer placement in their consultation room was significantly unfavorable
      to patient-physician communication. CONCLUSIONS: Physicians perceive the impact
      of computer use on patient-physician communication as negative, while patients
      have a positive perception of computer use on patient-physician communication.
      PRACTICE IMPLICATIONS: Consultation support can represent a challenge to
      physicians who recognize its negative impact in patient centered orientation.
      Medical education programs aiming to enhance specific communication skills and to
      better integrate computer use in primary care settings are needed.

PMID- 26215568
TI  - Paracrine signaling between tumor subclones of mouse SCLC: a critical role of ETS
      transcription factor Pea3 in facilitating metastasis.
AB  - Tumor heterogeneity can create a unique symbiotic tumor microenvironment.
      Earlier, we showed that clonal evolution in mouse small cell lung cancer (SCLC)
      can result in subclones that, upon cografting, endow the neuroendocrine tumor
      cells with metastatic potential. We now show that paracrine signaling between
      SCLC subclones is a critical requirement in the early steps of the metastatic
      process, such as local invasion and intravasation. We further show evidence that
      paracrine signaling via fibroblast growth factor 2 (Fgf2) and Mapk between these
      diverged tumor subclones causes enhanced expression of the Pea3 (polyomavirus
      enhancer activator 3) transcription factor, resulting in metastatic dissemination
      of the neuroendocrine tumor subclones. Our data reveal for the first time
      paracrine signaling between tumor cell subclones in SCLC that results in
      metastatic spread of SCLC. 

PMID- 26215572
TI  - Accurate diagnosis of patients' distress levels: The effect of family physicians'
      ability to take the patient's perspective.
AB  - OBJECTIVE: Previous research on diagnosis of distress among patients with
      physical ailments has focused on physicians who specialize in the treatment of
      chronic illness. This study explores family physicians' accuracy in diagnosing
      patients' emotional distress. METHODS: Questionnaires were administered to family
      physicians (N=61) and their patients (N=496) immediately after a medical
      encounter. Patients reported their distress levels. Physicians evaluated
      patients' distress levels and filled out a questionnaire measuring perspective
      taking, i.e., the tendency to perceive the point of view of others. RESULTS:
      Mixed model analyses of nested data showed a moderate positive relationship
      between physicians' evaluations of patients' distress and patients' self-reported
      distress. Diagnosis of distress was more accurate among family physicians with a
      better ability to take the patient's perspective. CONCLUSION: Family physicians'
      capacity to accurately diagnose patient distress is positively related to their
      ability to adopt patients' viewpoint. PRACTICE IMPLICATIONS: Family physicians'
      training should include enhancement of physicians' ability to take the patient's
      perspective.

PMID- 26215573
TI  - Shared decision making: Concepts, evidence, and practice.
AB  - OBJECTIVE: Shared decision-making (SDM) is advocated as the model for decision
      making in preference-sensitive decisions. In this paper we sketch the history of
      the concept of SDM, evidence on the occurrence of the steps in daily practice,
      and provide a clinical audience with communication strategies to support the
      steps involved. Finally, we discuss ways to improve the implementation of SDM.
      RESULTS: The plea for SDM originated almost simultaneously in medical ethics and
      health services research. Four steps can be distinguished: (1) the professional
      informs the patient that a decision is to be made and that the patient's opinion
      is important; (2) the professional explains the options and their pros and cons;
      (3) the professional and the patient discuss the patient's preferences and the
      professional supports the patient in deliberation; (4) the professional and
      patient discuss the patient's wish to make the decision, they make or defer the
      decision, and discuss follow-up. In practice these steps are seen to occur to a
      limited extent. DISCUSSION: Knowledge and awareness among both professionals and
      patients as well as tools and skills training are needed for SDM to become widely
      implemented. PRACTICE IMPLICATIONS: Professionals may use the steps and
      accompanying communication strategies to implement SDM.

PMID- 26215574
TI  - Environmental manipulation affects depressive-like behaviours in female Wistar
      Kyoto rats.
AB  - While the efficacy of pharmacological interventions to treat depression has been
      well-studied in animal models, much less work has been done to shed light on how
      changes in the immediate environment can impact behaviour. Furthermore, most
      studies have focused on male rodents despite the prevalence of mood disorders in
      women. In this study, 36 Wistar Kyoto (validated animal model of depression) and
      36 Wistar (control) female rats were used to examine the effects of environmental
      manipulation on depressive- and anxiety-like behaviours. Animals were assigned to
      one of three groups: standard (3 rats/cage), enriched (6 rats/cage plus physical
      enrichment), and isolation (1 rat/cage) housing. The elevated plus maze (EPM) and
      forced swim test (FST) were conducted prior to, and four weeks after
      environmental assignment to measure anxiety-like and depressive-like behaviours,
      respectively. Sucrose preference assessed anhedonia both before and after
      environmental assignment. Weight was measured every week to monitor weight-gain
      over time. Post-environment sucrose preference was significantly increased in
      animals in enriched housing as compared to those in isolated housing in both
      strains. While there were significant differences between strains in measures of
      open arm duration in the EPM and immobility in the FST, there appeared to be no
      differences between environmental groups. The results of this study highlight the
      importance of environmental factors in the expression of anhedonia. Enrichment
      appears to reduce anhedonia while isolation increases anhedonia. These effects
      should be studied further to assess whether longer periods of social and physical
      enrichment alleviate other symptoms of depression. 

PMID- 26215575
TI  - Shining light on memory: Effects of bright light on working memory performance.
AB  - This study examined whether diurnal non-image forming (NIF) effects of
      illuminance level on cognitive task performance depend on task difficulty and
      time of day. We employed a balanced crossover design with two 60-min sessions of
      200 vs. 1000 lux at eye level. Digit-span task difficulty was manipulated within
      subjects (forward (FDST) vs. backward (BDST) digit-span task), n-back task
      difficulty was manipulated between subjects (n=1, 2, or 3). Bright light exposure
      improved FDST performance during the final measurement block, especially in the
      afternoon. In contrast, BDST performance deteriorated slightly under bright light
      in the afternoon. Two-back performance was significantly worse under bright light
      in the afternoon, while no effect of illuminance level was found on 3-back
      performance. Thus, the more difficult BDST was affected differently by light
      intensity as compared to the easier FDST. N-back accuracy, however, did not
      confirm this role of task difficulty. Future studies should investigate whether
      similar results hold for other types of tasks and how other variables (e.g., time
      of day, physiological arousal, or other task characteristics) may influence the
      direction and magnitude of NIF effects on performance.

PMID- 26215576
TI  - Reply: To PMID 25784513.

PMID- 26215577
TI  - Age-associated reduction of cell spreading induces mitochondrial DNA common
      deletion by oxidative stress in human skin dermal fibroblasts: implication for
      human skin connective tissue aging.
AB  - BACKGROUND: Reduced cell spreading is a prominent feature of aged dermal
      fibroblasts in human skin in vivo. Mitochondrial DNA (mtDNA) common deletion has
      been reported to play a role in the human aging process, however the relationship
      between age-related reduced cell spreading and mtDNA common deletion has not yet
      been reported. RESULTS: To examine mtDNA common deletion in the dermis of aged
      human skin, the epidermis was removed from full-thickness human skin samples
      using cryostat. mtDNA common deletion was significantly elevated in the dermis of
      both naturally aged and photoaged human skin in vivo. To examine the relationship
      between age-related reduced cell spreading and mtDNA common deletion, we
      modulated the shape of dermal fibroblasts by disrupting the actin cytoskeleton.
      Reduced cell spreading was associated with a higher level of mtDNA common
      deletion and was also accompanied by elevated levels of endogenous reactive
      oxygen species (ROS). Boosting cellular antioxidant capacity by using
      antioxidants was found to be protective against mtDNA common deletion associated
      with reduced cell spreading. CONCLUSION: mtDNA common deletion is highly
      prevalent in the dermis of both naturally aged and photoaged human skin in vivo.
      mtDNA common deletion in response to reduced cell spreading is mediated, at least
      in part, by elevated oxidative stress in human dermal fibroblasts. These data
      extend current understanding of the mitochondrial theory of aging by identifying
      the connection between mtDNA common deletion and age-related reduction of cell
      spreading.

PMID- 26215578
TI  - Epiregulin contributes to breast tumorigenesis through regulating matrix
      metalloproteinase 1 and promoting cell survival.
AB  - BACKGROUND: The epidermal growth factor (EGF) family of ligands has been
      implicated in promoting breast cancer initiation, growth and progression. The
      contributions of EGF family ligands and their receptors to breast cancer are
      complex, and the specific mechanisms through which different ligands regulate
      breast tumor initiation and growth are not well-defined. These studies focus on
      the EGF family member epiregulin (EREG) as a mediator of early stage breast
      tumorigenesis. METHODS: EREG expression levels were assessed in both cell lines
      and human samples of ductal carcinoma in situ (DCIS) using quantitative RT-PCR,
      ELISA and immunohistochemistry. Gene knock-down approaches using shRNA-based
      strategies were used to determine the requirement of EREG for growth of MCF10DCIS
      cells in vivo, and for identifying mechanisms through which EREG promotes tumor
      cell survival. Experiments were performed using a combination of two-dimensional
      culture, three-dimensional culture and tumor growth in vivo. RESULTS: In
      comparison with other EGF family members, EREG was induced in MCF10DCIS cells
      compared with MCF10A and MCF10AT cells and its expression was partially regulated
      by fibroblast growth factor receptor (FGFR) activity. Reduced EREG expression in
      MCF10DCIS cells led to decreased tumor growth in vivo, which was associated with
      reduced cell survival. Furthermore, treatment of MCF10A cells with exogenous EREG
      enhanced cell survival both in three-dimensional culture and in response to
      chemotherapeutic agents. Examination of EREG-induced signaling pathways
      demonstrated that EREG promoted survival of MCF10A cells through regulating
      expression of matrix metalloproteinase-1 (MMP-1). To determine the relevance of
      these findings in human tumors, samples of DCIS were analyzed for EREG and MMP-1
      expression. EREG was induced in DCIS lesions compared to normal breast
      epithelium, and EREG and MMP-1 were correlated in a subset of DCIS samples.
      CONCLUSIONS: Together, these studies lead to identification of a novel pathway
      involving EREG and MMP-1 that contributes to the formation of early stage breast
      cancer. Understanding these complex pathways could ultimately lead to the
      development of novel biomarkers of neoplastic progression and/or new therapeutic
      strategies for patients with early stage cancer.

PMID- 26215579
TI  - Combinations of dexmedetomidine and alfaxalone with butorphanol in cats:
      application of an innovative stepwise optimisation method to identify optimal
      clinical doses for intramuscular anaesthesia.
AB  - OBJECTIVES: The aim of this study was to optimise dexmedetomidine and alfaxalone
      dosing, for intramuscular administration with butorphanol, to perform minor
      surgeries in cats. METHODS: Initially, cats were assigned to one of five groups,
      each composed of six animals and receiving, in addition to 0.3 mg/kg butorphanol
      intramuscularly, one of the following: (A) 0.005 mg/kg dexmedetomidine, 2 mg/kg
      alfaxalone; (B) 0.008 mg/kg dexmedetomidine, 1.5 mg/kg alfaxalone; (C) 0.012
      mg/kg dexmedetomidine, 1 mg/kg alfaxalone; (D) 0.005 mg/kg dexmedetomidine, 1
      mg/kg alfaxalone; and (E) 0.012 mg/kg dexmedetomidine, 2 mg/kg alfaxalone.
      Thereafter, a modified 'direct search' method, conducted in a stepwise manner,
      was used to optimise drug dosing. The quality of anaesthesia was evaluated on the
      basis of composite scores (one for anaesthesia and one for recovery), visual
      analogue scales and the propofol requirement to suppress spontaneous movements.
      The medians or means of these variables were used to rank the treatments;
      'unsatisfactory' and 'promising' combinations were identified to calculate,
      through the equation first described by Berenbaum in 1990, new dexmedetomidine
      and alfaxalone doses to be tested in the next step. At each step, five
      combinations (one new plus the best previous four) were tested. RESULTS: None of
      the tested combinations resulted in adverse effects. Four steps and 120 animals
      were necessary to identify the optimal drug combination (0.014 mg/kg
      dexmedetomidine, 2.5 mg/kg alfaxalone and 0.3 mg/kg butorphanol). CONCLUSIONS AND
      RELEVANCE: The investigated drug mixture, at the doses found with the
      optimisation method, is suitable for cats undergoing minor clinical procedures.

PMID- 26215581
TI  - Lobular breast cancer--the most common special subtype or a most special common
      subtype?
AB  - Lobular breast cancer is not only the second most common breast cancer subtype,
      known for decades, but also a tumour entity that still poses many unresolved
      questions. These include questions about the targets and cooperation partners of
      E-cadherin, the best model systems for translational research, and the best tools
      for detection, surveillance and therapy. Leading experts review the molecular and
      cellular bases, the model systems, the histopathology and profiling approaches,
      risk factors, imaging tools and therapeutic options for lobular breast cancer. 

PMID- 26215580
TI  - Adiponectin secreted by tubular renal cells during LPS exposure worsens the
      cellular inflammatory damage.
AB  - The pathogenetic role of adiponectin (ADPN) in kidney failure is not yet
      elucidated, since in vitro and in vivo studies have demonstrated that ADPN exerts
      both anti-inflammatory and pro-inflammatory effects. Starting from our previous
      findings demonstrating that HK-2 cells express and secrete ADPN, in this study we
      investigated the autocrine role of ADPN in tubular inflammatory damage induced by
      lipopolysaccharide (LPS) and the underlying molecular mechanisms. Firstly, we
      observed that short-term exposure to LPS enhanced ADPN protein expression as well
      as the adiponectin receptor ADIPOR1 mRNA content together with its signaling
      pathway downstream, pAMPK/pERK/pJNK, whose up-regulation status was reversed when
      ADPN gene knockdown occurred. Interestingly, in the same experimental conditions,
      we observed that ADPN mediated the nuclear translocation of the transcription
      factors nuclear factor kappa B (NFkB) and pcFos/pcJun (activator protein 1, AP
      1), both induced by the pJNK pathway and involved in tumor necrosis factor (TNF)
      alpha transactivation. Indeed, by transient transfection assay, we observed that
      the LPS-induced increase of TNF-alpha promoter activity was abrogated in cells
      pretreated with the inhibitors of NFkB and AP-1. Collectively our results suggest
      that in HK-2 cells, ADPN produced upon LPS stimulus could worsen the inflammatory
      damage in an autocrine-dependent manner.

PMID- 26215582
TI  - Effect of Prosthodontic Rehabilitation of Maxillary Defects on Hypernasality of
      Speech.
AB  - PURPOSE: To establish a correlation between the effective internal diameter of
      the maxillary defect, the resonating frequency, and the effectiveness of the
      definitive obturator in reducing the percentage nasality. MATERIALS AND METHODS:
      Twenty-nine patients who underwent maxillectomy confined only to the hard palate
      (Aramany's class I and class II defect) and were wearing a definitive obturator
      for at least 3 months were included. The percentage nasality and resonating
      frequency were calculated with the help of Praat software. The patients were
      asked to read out a "Rainbow" passage and also to phonate and articulate vowels.
      Both parameters were assessed with and without the obturator prosthesis. RESULTS:
      Following obturator use, a mean change of 1.07 +/- 0.83 kHz was observed in the
      resonating frequency (p < 0.001). The percentage change in resonating frequency
      was found to be 27.48 +/- 4.99% following obturator use (p < 0.001). The
      effective internal diameter of the maxillary defect was calculated with the help
      of a Vernier calliper. The correlation between absolute and percentage values of
      resonating frequency and nasality before and after obturator use was found to be
      negative. CONCLUSION: This study found that efficacy of the obturator prosthesis
      in reducing nasality was greater in smaller defects than in large defects.

PMID- 26215583
TI  - Impact of feeding tubes on prospective functional outcomes in patients with
      locally advanced head and neck cancer undergoing radiation therapy.
AB  - PURPOSE: The optimal timing of enteral feeding tube (FT) insertion during
      radiation therapy for head and neck cancer remains controversial. This study
      compares prospectively collected functional outcomes for prophylactic versus
      reactive insertion. METHODS AND MATERIALS: Patients undergoing primary radiation
      therapy for stage III-IV head and neck cancer between 2004 and 2009 underwent
      functional outcome assessment at baseline and 3, 6, 12, 24, and 36 months
      posttreatment. Instruments included the Royal Brisbane Hospital Outcome Measure
      for Swallowing, Performance Status Scale for Head and Neck Cancer Patients, and
      modified Edmonton Symptom Assessment Scale. Multivariable regression analysis was
      conducted to determine the impact of FT use on functional outcomes. RESULTS: A
      total of 178 patients were assessed with a median follow-up of 36.4 months. Use
      of an FT was prophylactic in 92 and reactive in 24; no tube was used in 62
      patients. Compared with prophylactic placement, reactive FT use was not
      associated with worse function for Performance Status Scale for Head and Neck
      Cancer Patients Normalcy of Diet for soft foods (adjusted odds ratio [AOR] 1.16,
      P = .85) or Eating in Public (AOR 1.87, P = .31). Similarly, there were no
      differences in the Royal Brisbane Hospital Outcome Measure for Swallowing for
      modified diet (AOR 1.27, P = .7) or FT dependence (AOR 3.01, P = .2).
      CONCLUSIONS: There were no significant differences in long-term swallowing
      function between patients who received a prophylactic versus reactive FT.

PMID- 26215584
TI  - Factors associated with event reporting in the pediatric radiation oncology
      population using an electronic incident reporting system.
AB  - PURPOSE: Pediatric patients may receive complex treatment. In our department, an
      electronic incident reporting system (condition reporting system [CRS]) was
      developed and made available to all members. METHODS AND MATERIALS: The CRS
      system is available on all departmental computers. Entered events are evaluated
      and graded by a supervisor as follows: "A"(dose deviation or patient harm), "B"
      (near miss), "C" (interruption in care process), or "D" (inconvenience). Data for
      pediatric patients for whom events were entered were reviewed retrospectively and
      compared to the entire treated pediatric population. RESULTS: Over 2 years, 503
      pediatric patients received radiation therapy (median age 10.1 years; range, 0.5
      18.8 years), and 592 pediatric CRS events were entered (9.8% of 6020 total
      institutional CRS entries). These concerned 275 patients with an average of 2.1
      entries each; 59% (348) were graded as severity D, 39% (230) as C, 2% (14) as B,
      and none as A. Events were most commonly related to treatment process (32%, n =
      188), followed by planning/dosimetry (19%, n = 109), anesthesia (15%, n = 86),
      scheduling/transport (13%, n = 73), and physics (10%, n = 62). Delays associated
      with events were <=1 hour for most cases (83%, n = 474). Patient and treatment
      factors associated with CRS entry included total duration of radiation therapy,
      primary brain tumor, receipt of proton therapy, and receipt of double-scattered
      proton therapy. No significant differences were found based on age, sex, race,
      treatment intent (curative vs palliative), type of photon treatment (conformal vs
      intensity modulated radiation therapy vs arc), use of total body irradiation, or
      use of pencil beam scanning proton therapy. CONCLUSIONS: An incident reporting
      system is a widely used part of the safety culture at our institution, which
      treats one of the largest pediatric patient volumes in North America. Most
      pediatric CRS-reported events are of minor severity. Longer treatment course and
      use of new and complex technologies appear to increase the likelihood of a CRS
      event within the pediatric population, which supports the need for increased
      safety processes when new techniques are initiated.

PMID- 26215585
TI  - Prospective contouring rounds: A novel, high-impact tool for optimizing quality
      assurance.
AB  - PURPOSE: This study was designed to present the results of a novel prospective
      contouring rounds (CR), in which peer review occurs once the contours and written
      directive are completed but before initiation of treatment planning. METHODS AND
      MATERIALS: Beginning in 2012, all patients undergoing conventionally fractionated
      radiation therapy at a high-volume academic center were reviewed in a newly
      initiated daily, prospective, multidisciplinary CR. Cases were scheduled for
      presentation 2 days after simulation with the expectation that contours would be
      complete. The clinical suitability of the clinical plan, prescription, contours,
      and written directive were evaluated and recorded in a prospective database.
      Treatment planning did not commence until CR approval. Patient information and
      the prospective database from the first 6 months since program inception, which
      represented 581 consecutive treatment plans, were pooled and analyzed
      retrospectively to determine the impact of the prospective peer review at this
      stage of care delivery. RESULTS: Sixty-four percent of cases were completed on
      time without correction. The remaining 36% of cases required modification before
      treatment planning was initiated. Incomplete contours, target-volume
      modifications, and alterations to the written directive were the most common
      corrections or reasons for delay. Decreasing rates of incomplete contours,
      contour modifications, and miscellaneous delays were seen over time as the
      program became established. The percentage of cases that had no delays or
      modifications increased continuously as the program matured in the first 6
      months, from 59% to 70%. CONCLUSIONS: Prospective CR is a meaningful and
      impactful tool in the quality assurance process. More than one-third of cases
      required contour, directive, or scheduling modification. The establishment of CR
      improved quality of care, with the percentage of timely, errorless cases
      increasing steadily over time. The impact of clinical peer review may be
      optimized by implementation at this early stage of delivery of care rather than
      at the time of traditional chart rounds.

PMID- 26215586
TI  - Automatic detection of patient identification and positioning errors in radiation
      therapy treatment using 3-dimensional setup images.
AB  - PURPOSE: To develop an automated system that detects patient identification and
      positioning errors between 3-dimensional computed tomography (CT) and kilovoltage
      CT planning images. METHODS AND MATERIALS: Planning kilovoltage CT images were
      collected for head and neck (H&N), pelvis, and spine treatments with
      corresponding 3-dimensional cone beam CT and megavoltage CT setup images from
      TrueBeam and TomoTherapy units, respectively. Patient identification errors were
      simulated by registering setup and planning images from different patients. For
      positioning errors, setup and planning images were misaligned by 1 to 5 cm in the
      6 anatomical directions for H&N and pelvis patients. Spinal misalignments were
      simulated by misaligning to adjacent vertebral bodies. Image pairs were assessed
      using commonly used image similarity metrics as well as custom-designed metrics.
      Linear discriminant analysis classification models were trained and tested on the
      imaging datasets, and misclassification error (MCE), sensitivity, and specificity
      parameters were estimated using 10-fold cross-validation. RESULTS: For patient
      identification, our workflow produced MCE estimates of 0.66%, 1.67%, and 0% for
      H&N, pelvis, and spine TomoTherapy images, respectively. Sensitivity and
      specificity ranged from 97.5% to 100%. MCEs of 3.5%, 2.3%, and 2.1% were obtained
      for TrueBeam images of the above sites, respectively, with sensitivity and
      specificity estimates between 95.4% and 97.7%. MCEs for 1-cm H&N/pelvis
      misalignments were 1.3%/5.1% and 9.1%/8.6% for TomoTherapy and TrueBeam images,
      respectively. Two-centimeter MCE estimates were 0.4%/1.6% and 3.1/3.2%,
      respectively. MCEs for vertebral body misalignments were 4.8% and 3.6% for
      TomoTherapy and TrueBeam images, respectively. CONCLUSIONS: Patient
      identification and gross misalignment errors can be robustly and automatically
      detected using 3-dimensional setup images of different energies across 3 commonly
      treated anatomical sites.

PMID- 26215588
TI  - Regulation of acetylcholine receptors during differentiation of bone mesenchymal
      stem cells harvested from human reaming debris.
AB  - Acetylcholine (ACh) is an important signaling molecule in non-neuronal systems
      where it is involved in regulation of viability, proliferation, differentiation
      and migration of mesenchymal stem cells (MSC) that are capable to differentiate
      into osteoblasts, chondrocytes and adipocytes. Patients with the systemic disease
      osteoporosis show altered MSC properties, reduced bone formation and mineral
      density followed by increased bone fragility and high fracture incidence. Here we
      asked whether nicotinic and muscarinic acetylcholine receptors (AChR) are
      expressed in osteoblasts, adipocytes and chondrocytes differentiated from bone
      MSC extracted from human reaming debris (RDMSC) that was harvested during surgery
      of long bone diaphyseal fractures. Using RT-PCR, AChR were detected in RDMSC,
      osteoblasts, chondrocytes and adipocytes of male and female bone-healthy and of
      female osteoporotic donors. An up-regulation in multiplicity and occurrence of
      AChR subtypes was found in female compared to male donors and in osteoblast of
      male donors compared to adipocytes. Real-time RT-PCR analysis resulted in a
      significant increase in relative expression of nAChR alpha9 in chondrocytes
      compared to adipocytes of healthy female donors. The nAChR subunit alpha10 was
      significantly up-regulated in osteoblasts of healthy compared to osteoporotic
      donors as well as the mAChR M5 that is additionally decreased in osteoporotic
      osteoblasts compared to MSC and chondrocytes of osteoporotic donors. In summary,
      the gene expression of AChR during differentiation of RDMSC and its regulation in
      cells of osteoporotic donors lead to the assumption that AChR signaling is
      involved in bone formation and might be utilized to stimulate bone remodeling
      processes. 

PMID- 26215587
TI  - Association between acetylsalicylic acid and the risk of dialysis-related
      infections or septicemia among incident hemodialysis patients: a nested case
      control study.
AB  - BACKGROUND: Vascular access-related infections and septicemia are the main causes
      of infections among hemodialysis patients, the majority of them caused by
      Staphylococcus species. Acetylsalicylic acid (ASA) has recently been reported
      with a probable antistaphylococcal activity. This study aimed to evaluate the
      effect of ASA on the risk of dialysis-related infection and septicemia among
      incident chronic hemodialysis patients. METHODS: In a nested case-control study,
      we identified 449 cases of vascular access-related infections and septicemia, and
      4156 controls between 2001 and 2007 from our incident chronic hemodialysis
      patients' cohort. Cases were defined as patients hospitalized with a main
      diagnosis of vascular access-related infection or septicemia on the discharge
      sheet (ICD-9 codes). Up to ten controls per case were selected by incidence
      density sampling and matched to cases on age, sex and follow-up time. ASA
      exposure was measured at the admission and categorized as: no use, low dose (80
      324 mg/d), high dose (>=325 mg/d). Odds ratios (OR) for infections were estimated
      using multivariable conditional logistic regression analysis, adjusting for
      potential confounders. RESULTS: Compared to no use, neither dose of ASA was
      associated with a decreased risk of infection: low dose (OR 1.03, 95 % CI 0.82
      1.28) and high dose (OR 1.30, 95 % CI 0.96-1.75). However, diabetes (OR = 1.32,
      95 % CI = 1.07-1.62) and anticoagulant use (OR = 1.62, 95 % CI = 1.30-2.02) were
      associated with a higher risk. CONCLUSION: Among hemodialysis patients, ASA use
      was not associated with a reduced risk of hospitalizations for dialysis-related
      infections or septicemia. However, ASA may remain beneficial for its
      cardiovascular indications.

PMID- 26215590
TI  - An Illness of Power: Gender and the Social Causes of Depression.
AB  - There is considerable discourse surrounding the disproportionate diagnosis of
      women with depression as compared to men, often times cited at a rate around 2:1.
      While this disparity clearly draws attention to gender, a focus on gender tends
      to fall away in the study and treatment of depression in neuroscience and
      psychiatry, which largely understand its workings in mechanistic terms of brain
      chemistry and neurological processes. I first consider how this brain-centered
      biological model for depression came about. I then argue that the authoritative
      scientific models for disorder have serious consequences for those diagnosed.
      Finally, I argue that mechanistic biological models of depression have the effect
      of silencing women and marginalizing or preventing the examination of social
      structural causes of depression, like gender oppression, and therein contribute
      to the ideological reproduction of oppressive social relations. I argue that
      depression is best understood in terms of systems of power, including gender, and
      where a given individual is situated within such social relations. The result is
      a model of depression that accounts for the influence of biological,
      psychological, and social factors. 

PMID- 26215589
TI  - Design and baseline characteristics of the PerfectFit study: a multicenter
      cluster-randomized trial of a lifestyle intervention in employees with increased
      cardiovascular risk.
AB  - BACKGROUND: The prevalence of unhealthy lifestyles and preventable chronic
      diseases is high. They lead to disabilities and sickness absence, which might be
      reduced if health promotion measures were applied. Therefore, we developed the
      PerfectFit health promotion intervention with a "blended care"-approach, which
      consists of a web-based health risk assessment (HRA) including tailored and
      personalized advice, followed by motivational interviewing (MI). We hypothesize
      that adding MI to a web-based HRA leads to better health outcomes. The objective
      is to describe the design and baseline characteristics of the PerfectFit study,
      which is being conducted among employees with high cardiovascular risk in the
      military workforce, the police organization and an academic hospital. METHODS:
      PerfectFit is a cluster randomized controlled trial, consisting of two arms.
      Based on cardiovascular risk profiling, done between 2012 and 2014, we included
      employees based on one or more risk factors and motivation to participate. One
      arm is the 'limited' health program (control) that consists of: (a) an HRA as a
      decision aid for lifestyle changes, including tailored and personalized advice,
      and pros and cons of the options, and (b) a newsletter every 3 months. The other
      arm is the 'extensive' program (intervention), which is additionally offered MI
      sessions by trained occupational physicians, 4 face-to-face and 3 by telephone,
      and is offered more choices of health promotion activities in the HRA. During the
      follow-up period, participants choose the health promotion activities they
      personally prefer. After six and twelve months, outcomes will be assessed by
      online questionnaires. After twelve months the cardiovascular risk profiling will
      be repeated. The primary outcome is self-reported general health. Secondary
      outcomes are self-reported work ability, CVD-risk score, sickness absence,
      productivity loss at work, participation in health promotion activities, changes
      in lifestyle (smoking, alcohol consumption, physical activity, stress management)
      and body mass index. Furthermore, a process evaluation and an economic analysis
      will be performed. DISCUSSION: Additional coaching using MI is expected to be a
      key factor for success of the web-based HRA in employees with increased
      cardiovascular risk. This "blended care"-approach may be an essential strategy
      for effective health promotion activities. TRIAL REGISTRATION: Dutch Trial
      Register by registration number NTR4894 , 14/11/2014.

PMID- 26215591
TI  - Ethical decision making in dental education: a preliminary study.
AB  - BACKGROUND: In terms of ethical decision making, every clinical case, when seen
      as an ethical problem, may be analyzed by means of four topics: medical
      indications, patient preferences, quality of life, contextual features. The aim
      of this study was to compare the performance of 4th year dental students on
      Ethical Decision Making before and after a course on ethics. METHODS: Fourth year
      dental students (n = 37) from academic year 2013-2014 participated in the study.
      A 3-h lecture, which was about four topics approach to clinical ethical case
      analysis, was given to the students. The lecture was based on case scenarios
      related with dental ethics. After the completion of lectures,a case scenario was
      presented to the students to assess their ethical decision making abilities. At
      the end of the exam, four topics and ethical judgment were evaluated. Their
      performances on this examination were evaluated before and after lectures.
      Statistical evaluation was performed with the significance level set at p < 0.05.
      RESULTS: A statistically significant difference was found between the means of
      four topics (p < 0.05). There was no statistically significant difference between
      the mean scores of judgment of ethical decision (p > 0.05). The mean total score
      of the students after the course was significantly higher than before course
      (67.5 and 54.4, respectively; p < 0.05). CONCLUSION: More lectures should be
      implemented to the curriculum to increase the student awareness of ethical issues
      and to reach the ultimate goals of dental education.

PMID- 26215592
TI  - The Cipher Code of Simple Sequence Repeats in "Vampire Pathogens".
AB  - Blood inside mammals is a forbidden area for the majority of prokaryotic
      microbes; however, red blood cells tropism microbes, like "vampire pathogens"
      (VP), succeed in matching scarce nutrients and surviving strong immunity
      reactions. Here, we found VP of Mycoplasma, Rhizobiales, and Rickettsiales showed
      significantly higher counts of (AG)n dimeric simple sequence repeats (Di-SSRs) in
      the genomes, coding and non-coding regions than non Vampire Pathogens (N_VP).
      Regression analysis indicated a significant correlation between GC content and
      the span of (AG)n-Di-SSR variation. Gene Ontology (GO) terms with abundance of
      (AG)3-Di-SSRs shared by the VP strains were associated with purine nucleotide
      metabolism (FDR < 0.01), indicating an adaptation to the limited availability of
      purine and nucleotide precursors in blood. Di-amino acids coded by (AG)n-Di-SSRs
      included all three six-fold code amino acids (Arg, Leu and Ser) and significantly
      higher counts of Di-amino acids coded by (AG)3, (GA)3, and (TC)3 in VP than N_VP.
      Furthermore, significant differences (P < 0.001) on the numbers of triplexes
      formed from (AG)n-Di-SSRs between VP and N_VP in Mycoplasma suggested the
      potential role of (AG)n-Di-SSRs in gene regulation.

PMID- 26215593
TI  - Delivering thrombectomy for acute stroke using cardiology services.

PMID- 26215594
TI  - New grassroots movement aims to champion general practice.

PMID- 26215596
TI  - Carotid Intima Media Thickness in Mainly Female HIV-Infected Subjects in Rural
      South Africa: Association With Cardiovascular but Not HIV-Related Factors.
AB  - BACKGROUND: In sub-Saharan Africa, the number of persons living with human
      immunodeficiency virus (HIV) has increased immensely. In parallel, rates of
      noncommunicable diseases, especially cardiovascular disease, are rising rapidly
      in resource-limited settings. This study aims to evaluate the relation between
      subclinical atherosclerosis and HIV-related and traditional cardiovascular risk
      factors in HIV-infected patients in rural South Africa. METHODS: A cross
      sectional study was performed among HIV-infected patients visiting a health
      center in Limpopo, South Africa. Demographic and HIV-related information was
      collected, and cardiovascular risk was assessed. Carotid intima media thickness
      (CIMT) was measured and the prevalence of subclinical atherosclerosis (CIMT >0.78
      mm) was calculated. The association between cardiovascular or HIV-related
      determinants with CIMT was analyzed using linear and logistic regression models
      adjusted for age and sex. RESULTS: The median CIMT in 866 subjects (median age
      [interquartile range], 41 [35-48] years; 69% female) was 0.589 mm (interquartile
      range, 0.524-0.678 mm), and values seemed higher than in healthy Western
      reference populations. In fact 12% of subjects (106 of 866) had subclinical
      atherosclerosis. Hypertension, high body mass index, previous cardiovascular
      event, diabetes mellitus, total and low-density lipoprotein cholesterol,
      estimated glomerular filtration rate, metabolic syndrome, and the Framingham
      Heart Risk score were independently associated with CIMT. No HIV-related
      determinants were associated with CIMT. CONCLUSIONS: In a predominantly female
      HIV-infected population in South Africa, CIMT values are considerably high and
      associated with cardiovascular risk factors, rather than HIV-related factors.
      This finding emphasizes the need to screen for cardiovascular disease among
      persons with HIV infection in resource-limited settings. Ideally, this screening
      would be integrated into care for chronic HIV infection, posing a major challenge
      for the future.

PMID- 26215595
TI  - Comprehensive meta-analysis, co-expression, and miRNA nested network analysis
      identifies gene candidates in citrus against Huanglongbing disease.
AB  - BACKGROUND: Huanglongbing (HLB), the most devastating disease of citrus, is
      associated with infection by Candidatus Liberibacter asiaticus (CaLas) and is
      vectored by the Asian citrus psyllid (ACP). Recently, the molecular basis of
      citrus-HLB interactions has been examined using transcriptome analyses, and these
      analyses have identified many probe sets and pathways modulated by CaLas
      infection among different citrus cultivars. However, lack of consistency among
      reported findings indicates that an integrative approach is needed. This study
      was designed to identify the candidate probe sets in citrus-HLB interactions
      using meta-analysis and gene co-expression network modelling. RESULTS: Twenty-two
      publically available transcriptome studies on citrus-HLB interactions, comprising
      18 susceptible (S) datasets and four resistant (R) datasets, were investigated
      using Limma and RankProd methods of meta-analysis. A combined list of 7,412
      differentially expressed probe sets was generated using a Teradata in-house
      Structured Query Language (SQL) script. We identified the 65 most common probe
      sets modulated in HLB disease among different tissues from the S and R datasets.
      Gene ontology analysis of these probe sets suggested that carbohydrate
      metabolism, nutrient transport, and biotic stress were the core pathways that
      were modulated in citrus by CaLas infection and HLB development. We also
      identified R-specific probe sets, which encoded leucine-rich repeat proteins,
      chitinase, constitutive disease resistance (CDR), miraculins, and lectins.
      Weighted gene co-expression network analysis (WGCNA) was conducted on 3,499 probe
      sets, and 21 modules with major hub probe sets were identified. Further, a miRNA
      nested network was created to examine gene regulation of the 3,499 target probe
      sets. Results suggest that csi-miR167 and csi-miR396 could affect ion
      transporters and defence response pathways, respectively. CONCLUSION: Most of the
      potential candidate hub probe sets were co-expressed with gibberellin pathway
      (GA)-related probe sets, implying the role of GA signalling in HLB resistance.
      Our findings contribute to the integration of existing citrus-HLB transcriptome
      data that will help to elucidate the holistic picture of the citrus-HLB
      interaction. The citrus probe sets identified in this analysis signify a robust
      set of HLB-responsive candidates that are useful for further validation.

PMID- 26215597
TI  - Arsenic trioxide regulates adipogenic and osteogenic differentiation in bone
      marrow MSCs of aplastic anemia patients through BMP4 gene.
AB  - The typical pathological feature of aplastic anemia (AA) is the rise in the
      number of fat cells and the reduction of osteoblasts in bone marrow. However,
      both fat cells and osteobalsts in bone marrow are derived from the mesenchymal
      stem cells (MSCs). Generally, the adipogenic and osteogenic differentiation is a
      dynamic and balanceable process. The imbalance of the adipogenic and osteogenic
      differentiation may participate in the occurrence and progress of many diseases.
      Arsenic trioxide (ATO) could induce differentiation and apoptosis in tumor cells.
      In this study, Oil Red-O and Alizarin red were used to detect the adipogenic and
      osteogenic differentiation. The ability of adipogenic differentiation is much
      higher, whereas the osteogenic differentiation is much lower in the MSCs of AA
      patients compared with healthy controls. ATO inhibits adipogenic differentiation
      and promotes osteogenic differentiation in the MSC of AA patients. The expression
      of BMP4 is increased with ATO treatment. The ability of adipogenic
      differentiation is decreased, whereas the osteogenic differentiation is increased
      after transfection of BMP4 gene into the MSCs of AA patients. This study shows
      that ATO regulates the adipogenic and osteogenic differentiation balance of MSCs
      in AA, which provides a theoretical basis for the adjunctive therapy of ATO on
      AA. The BMP4 gene is involved in the ATO regulation of adipogenic and osteogenic
      differentiation balance, which provides a new target for the treatment of AA. 

PMID- 26215598
TI  - Synthetic sialylglycopolymer receptor for virus detection using cantilever-based
      sensors.
AB  - We describe the rapid, label-free detection of Influenza A viruses using a
      cantilever transducer modified with a synthetic sialylglycopolymer receptor
      layer. Surface stresses induced by viruses binding to the receptor layer were
      used as the analytical signal. The synthetic sialylglycopolymer receptor layer
      can be used in nanoscale strain-gauge cantilever transducers for highly sensitive
      virus detection. Strain-gage transducers using such sensor layers exhibit long
      lifetimes, high sensitivities, and possible regeneration. Nanomechanical
      cantilever systems using optical detectors were used for the surface stress
      measurements. We demonstrated the positive, label-free detection of Influenza A
      at concentrations below 10(6) viruses per ml. In contrast to hemagglutination
      assays, cantilever sensors are label free, in situ, and rapid (less than 30 min),
      and they require minimal or nearly no sample preparation. 

PMID- 26215599
TI  - Enculturating science: Community-centric design of behavior change interactions
      for accelerating health impact.
AB  - Despite significant advancements in the scientific evidence base of interventions
      to improve newborn survival, we have not yet been able to "bend the curve" to
      markedly accelerate global rates of reduction in newborn mortality. The ever
      widening gap between discovery of scientific best practices and their mass
      adoption by families (the evidence-practice gap) is not just a matter of
      improving the coverage of health worker-community interactions. The design of the
      interactions themselves must be guided by sound behavioral science approaches
      such that they lead to mass adoption and impact at a large scale. The main
      barrier to the application of scientific approaches to behavior change is our
      inability to "unbox" the "black box" of family health behaviors in community
      settings. The authors argue that these are not black boxes, but in fact
      thoughtfully designed community systems that have been designed and upheld, and
      have evolved over many years keeping in mind a certain worldview and a common
      social purpose. An empathetic understanding of these community systems allows us
      to deconstruct the causal pathways of existing behaviors, and re-engineer them to
      achieve desired outcomes. One of the key reasons for the failure of interactions
      to translate into behavior change is our failure to recognize that the content,
      context, and process of interactions need to be designed keeping in mind an
      organized community system with a very different worldview and beliefs. In order
      to improve the adoption of scientific best practices by communities, we need to
      adapt them to their culture by leveraging existing beliefs, practices, people,
      context, and skills. The authors present a systems approach for community-centric
      design of interactions, highlighting key principles for achieving intrinsically
      motivated, sustained change in social norms and family health behaviors,
      elucidated with progressive theories from systems thinking, management sciences,
      cross-cultural psychology, learning and social cognition, and the behavioral
      sciences. These are illustrated through a case study of designing effective
      interactions in Shivgarh, India, that led to rapid and substantial changes in
      newborn health behaviors and reduction in NMR by half over a span of 16 months. 

PMID- 26215600
TI  - Re: Scott A. Tomlins, John R. Day, Robert J. Lonigro, et al. Urine TMPRSS2:ERG
      Plus PCA3 for Individualized Prostate Cancer Risk Assessment. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2015.04.039.

PMID- 26215601
TI  - Reply to Per-Uno Malmstrom and Bruce J. Trock's Letter to the Editor re: Richard
      J. Sylvester, Willem Oosterlinck, Sten Holmang, et al. Systematic Review and
      Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single
      Immediate Instillation of Chemotherapy After Transurethral Resection with
      Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma
      of the Bladder: Which Patients Benefit from the Instillation? Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2015.05.050.

PMID- 26215602
TI  - Re: Robert J. van Soest, Ellen S. de Morree, Charlotte F. Kweldam, et al.
      Targeting the Androgen Receptor Confers In Vivo Cross-resistance Between
      Enzalutamide and Docetaxel, But Not Cabazitaxel, in Castration-resistant Prostate
      Cancer. Eur Urol 2015;67:981-5.

PMID- 26215603
TI  - Re: Richard J. Sylvester, Willem Oosterlinck, Sten Holmang, et al. Systematic
      Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a
      Single Immediate Instillation of Chemotherapy After Transurethral Resection with
      Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma
      of the Bladder: Which Patients Benefit from the Instillation? Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2015.05.050.

PMID- 26215604
TI  - Accuracy of Magnetic Resonance Imaging for Local Staging of Prostate Cancer: A
      Diagnostic Meta-analysis.
AB  - CONTEXT: Correct assessment of tumour stage is crucial for prostate cancer (PCa)
      management. OBJECTIVE: To assess the diagnostic accuracy of magnetic resonance
      imaging (MRI) for local PCa staging and explore the influence of different
      imaging protocols. EVIDENCE ACQUISITION: We searched the PubMed, Embase, and
      Cochrane databases from 2000 up to August 2014. We included studies that used MRI
      for detection of extracapsular extension (ECE; T3a), seminal vesicle invasion
      (SVI; T3b), or overall stage T3 PCa, with prostatectomy as the reference
      standard. Methodologic quality was assessed using the Quality Assessment of
      Diagnostic Accuracy Studies tool by two independent reviewers. Data necessary to
      complete 2*2 tables were obtained, and patient, study, and imaging
      characteristics were extracted. Accuracy was reported for the most experienced or
      first reader. Results were pooled and plotted in summary receiver operating
      characteristics plots. EVIDENCE SYNTHESIS: A total of 75 studies (9796 patients)
      could be analysed. Pooled data for ECE (45 studies, 5681 patients), SVI (34
      studies, 5677 patients), and overall stage T3 detection (38 studies, 4001
      patients) showed sensitivity and specificity of 0.57 (95% confidence interval
      [CI] 0.49-0.64) and 0.91 (95% CI 0.88-0.93), 0.58 (95% CI 0.47-0.68) and 0.96
      (95% CI 0.95-0.97), and 0.61 (95% CI 0.54-0.67) and 0.88 (95% CI 0.85-0.91),
      respectively. Functional imaging in addition to T2-weighted imaging and use of
      higher field strengths (3 T) improved sensitivity for ECE and SVI. ECE
      sensitivity was not improved by endorectal coil use. CONCLUSIONS: MRI has high
      specificity but poor and heterogeneous sensitivity for local PCa staging. An
      endorectal coil showed no additional benefit for ECE detection, but slightly
      improved sensitivity for SVI detection. Higher field strengths and the use of
      functional imaging techniques can slightly improve sensitivity. PATIENT SUMMARY:
      We pooled the results from all previous studies that evaluated magnetic resonance
      imaging (MRI) for detection of tumour growth outside the prostate. MRI is not
      sensitive enough to find all tumours with extraprostatic growth.

PMID- 26215606
TI  - On Molecular Classification of Bladder Cancer: Out of One, Many.
AB  - Comparative analysis showed that bladder cancer classification systems identify
      overlapping subtypes but at different levels. Muscle-invasive bladder cancer
      shows remarkable heterogeneity, and six subtypes were identified that differ in
      transcriptional networks, marker profiles, and expression of actionable targets. 

PMID- 26215605
TI  - Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma.
AB  - BACKGROUND: Metastatic renal cell carcinoma (mRCC) patients receiving first-line
      sunitinib typically survive >2 yr, with chronic treatment sometimes extending to
      >=6 yr. OBJECTIVE: To analyze long-term safety with sunitinib in mRCC patients.
      DESIGN, SETTING, AND PARTICIPANTS: Data were pooled from 5739 patients in nine
      trials, comprising seven phase II studies, a phase III study, and an expanded
      access trial in various treatment settings (e.g., cytokine refractory or
      treatment-naive). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Interval and
      cumulative time-period analyses evaluated the incidence of treatment-related
      adverse events (TRAEs) for up to 6 yr, in the overall population and in those
      with long-term (>=2 yr) sunitinib treatment. RESULTS AND LIMITATIONS: Among long
      term patients (n=807), most TRAEs occurred initially in the first year and then
      decreased in frequency; TRAEs following this pattern included decreased appetite,
      diarrhea, dysgeusia, dyspepsia, fatigue, hypertension, mucosal inflammation,
      nausea, and stomatitis. However, hypothyroidism increased by interval analysis
      from 6% at 0-<6 mo to 42% at 5-<6 yr and by cumulative analysis from 14% at 0-<1
      yr to 36% over 6 yr. Grade 3/4 TRAEs in long-term patients peaked during the
      first year and then steadily decreased. The overall population displayed only
      minor differences from long-term patients, with no clinically significant
      differences between grade >=3 TRAE profiles (<5% difference in incidence rates at
      all intervals). Limitations included retrospective design, assessment
      variability, lack of pharmacokinetic data, and absence of baseline
      characteristics for long-term patients. CONCLUSIONS: Prolonged sunitinib was not
      associated with new types or increased severity of TRAEs. Except hypothyroidism,
      toxicity was not cumulative. PATIENT SUMMARY: More than 800 mRCC patients
      received sunitinib for between 2 and 6 yr without experiencing new or more severe
      treatment-related toxicity. Clinicians may be able to prescribe chronic sunitinib
      treatment for as long as patients continue to derive clinical benefit, without
      untoward additional risk.

PMID- 26215607
TI  - The Evolution of Active Surveillance for Prostate Cancer.

PMID- 26215608
TI  - Totally Robotic Approach with Transvaginal Insertion for Kidney Transplantation.

PMID- 26215609
TI  - Re: Johan Lindberg, Anna Kristiansen, Peter Wiklund, Henrik Gronberg, Lars
      Egevad. Tracking the Origin of Metastatic Prostate Cancer. Eur Urol 2015;67:819
      22.

PMID- 26215611
TI  - Improving Outcomes from Prostate Cancer: Unlocking the Treasure Trove of
      Information in Cancer Registries.

PMID- 26215610
TI  - The UGT2B28 Sex-steroid Inactivation Pathway Is a Regulator of Steroidogenesis
      and Modifies the Risk of Prostate Cancer Progression.
AB  - BACKGROUND: Androgen inactivation occurs mainly through the glucuronidation
      conjugative reaction mediated by UDP-glucuronosyltransferases (UGTs). This
      metabolic process is involved in the control of systemic and local androgen
      bioavailability. OBJECTIVE: To examine the relationship among expression of the
      androgen-inactivating UGT2B28 enzyme, circulating steroid hormone levels, and
      clinical phenotype in prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS:
      We conducted an analysis of a high-density prostate tumor tissue microarray
      consisting of 239 localized PCa cases. The study of 51 additional PCa patients
      with no copies of UDP glucuronosyltransferase 2B subfamily, polypeptide B28
      (UGT2B28) in their genomes was performed to confirm the importance of the enzyme
      on circulating hormone levels. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      Steroid hormones were measured by mass spectrometry. Multivariate Cox
      proportional hazard models assessed the influence of UGT2B28 on progression, and
      general linear model regression evaluated variations in hormone levels. RESULTS
      AND LIMITATIONS: Tumor overexpression of UGT2B28 was associated with lower
      prostate-specific antigen levels at diagnosis, higher Gleason scores, margin and
      nodal invasion status, and it was shown to be an independent prognostic factor
      associated with progression. Enzyme overexpression correlated with 30% higher
      circulating levels of testosterone (T) and dihydrotestosterone (DHT). Patients
      with no copies of UGT2B28 in their genomes have lower levels of T (19%), DHT
      (17%), its glucuronide metabolites (18-38%), and enhanced levels of the adrenal
      precursor androstenedione (36%). CONCLUSIONS: The UGT2B28 steroid-inactivating
      pathway modifies circulating T and DHT levels, and UGT2B28 overexpression is
      associated with high-grade PCa. Our work has uncovered the role of UGT2B28 as a
      regulator of steroidogenesis and underscores the interconnectivity among the
      steroid-inactivation capacity of cancer cells, hormone levels, disease
      characteristics, and the risk of cancer progression. PATIENT SUMMARY: The
      androgen-inactivating UGT2B28 enzyme influences hormone levels, clinical and
      pathologic factors, and the risk of cancer progression.

PMID- 26215612
TI  - Oral Nadolol for the Treatment of Infantile Hemangiomas: A Single-Institution
      Retrospective Cohort Study.
AB  - BACKGROUND: Beta-blockers have become the treatment of choice for problematic
      infantile hemangiomas (IHs). Nadolol, a nonselective beta-blocker with potential
      dosing advantages and a better safety profile than that of other beta-blockers,
      has been studied as an alternative therapeutic option. Our objective was to
      characterize the efficacy and safety of oral nadolol in the treatment of
      proliferating IHs. METHODS: A retrospective cohort study was conducted at the
      Hospital for Sick Children between February 2010 and April 2012 in patients
      treated with nadolol for proliferating IHs causing functional impairment or
      cosmetic disfigurement. The primary outcome was the percentage involution
      measured independently by two assessors who scored changes in the extent of IHs
      by comparing serial photographs using a 100-mm visual analogue scale (VAS), on
      which 5 mm represented 10% change. RESULTS: Forty-four patients treated with
      nadolol for IHs with adequate photographic documentation were identified. The
      median age at presentation was 4.5 months (interquartile range 1.5-7.9 mos).
      There was a mean improvement of 91.8 +/- 11.1%. At least 50% improvement was
      noted in 42 (95%) patients and 75% improvement in 39 (89%) patients. The mean
      time to 50% and 75% improvement was 2.9 and 3.7 months, respectively. Analysis of
      variance showed that younger age at the time of treatment start was associated
      with a higher mean VAS score (% involution) (p < 0.05). Treatment duration (mean
      9.5 +/- 5.6 months) had no significant effect on VAS score. Test of interobserver
      correlation showed good agreement (intraclass correlation coefficient = 0.86, p =
      0.001). CONCLUSIONS: Oral nadolol is efficacious in patients with problematic
      IHs. Further large-scale prospective comparative studies are warranted to compare
      nadolol with other beta-blockers.

PMID- 26215613
TI  - Impact of intra-operative intraperitoneal chemotherapy on organ/space surgical
      site infection in patients with gastric cancer.
AB  - BACKGROUND: Various risk factors for surgical site infection (SSI) have been
      identified such as age, overweight, duration of surgery, blood loss, etc.
      Intraperitoneal chemotherapy during surgery is a common procedure in patients
      with gastric cancer, yet its impact on SSI has not been evaluated. AIM: To
      evaluate whether intra-operative intraperitoneal chemotherapy is a key risk
      factor for organ/space SSI in patients with gastric cancer. METHODS: All patients
      with gastric cancer who underwent surgery at the Department of Gastrointestinal
      Surgery between January 2008 and December 2013 were studied. The organ/space SSI
      rates were compared between patients who received intra-operative intraperitoneal
      chemotherapy and patients who did not receive intra-operative intraperitoneal
      chemotherapy, and the risk factors for organ/space SSI were analysed by
      univariate and multi-variate regression analyses. The microbial causes of
      organ/space SSI were also identified. FINDINGS: Of the eligible 845 patients, 356
      received intra-operative intraperitoneal chemotherapy, and the organ/space SSI
      rate was higher in these patients compared with patients who did not receive
      intra-operative intraperitoneal chemotherapy (9.01% vs 3.88%; P = 0.002).
      Univariate analysis confirmed the significance of this finding (odds ratio 2.443;
      P = 0.003). As a result, hospital stay was increased in patients who received
      intra-operative intraperitoneal chemotherapy {mean 20.91 days [95% confidence
      interval (CI) 19.76-22.06] vs 29.72 days (95% CI 25.46-33.99); P = 0.000}. The
      results also suggested that intra-operative intraperitoneal chemotherapy may be
      associated with more Gram-negative bacterial infections. CONCLUSION: Intra
      operative intraperitoneal chemotherapy is a significant risk factor for
      organ/space SSI in patients with gastric cancer.

PMID- 26215614
TI  - A biphasic epigenetic switch controls immunoevasion, virulence and niche
      adaptation in non-typeable Haemophilus influenzae.
AB  - Non-typeable Haemophilus influenzae contains an N(6)-adenine DNA
      methyltransferase (ModA) that is subject to phase-variable expression (random
      ON/OFF switching). Five modA alleles, modA2, modA4, modA5, modA9 and modA10,
      account for over two-thirds of clinical otitis media isolates surveyed. Here, we
      use single molecule, real-time (SMRT) methylome analysis to identify the DNA
      recognition motifs for all five of these modA alleles. Phase variation of these
      alleles regulates multiple proteins including vaccine candidates, and key
      virulence phenotypes such as antibiotic resistance (modA2, modA5, modA10),
      biofilm formation (modA2) and immunoevasion (modA4). Analyses of a modA2 strain
      in the chinchilla model of otitis media show a clear selection for ON switching
      of modA2 in the middle ear. Our results indicate that a biphasic epigenetic
      switch can control bacterial virulence, immunoevasion and niche adaptation in an
      animal model system. 

PMID- 26215615
TI  - Structures of the Ultra-High-Affinity Protein-Protein Complexes of Pyocins S2 and
      AP41 and Their Cognate Immunity Proteins from Pseudomonas aeruginosa.
AB  - How ultra-high-affinity protein-protein interactions retain high specificity is
      still poorly understood. The interaction between colicin DNase domains and their
      inhibitory immunity (Im) proteins is an ultra-high-affinity interaction that is
      essential for the neutralisation of endogenous DNase catalytic activity and for
      protection against exogenous DNase bacteriocins. The colicin DNase-Im interaction
      is a model system for the study of high-affinity protein-protein interactions.
      However, despite the fact that closely related colicin-like bacteriocins are
      widely produced by Gram-negative bacteria, this interaction has only been studied
      using colicins from Escherichia coli. In this work, we present the first crystal
      structures of two pyocin DNase-Im complexes from Pseudomonas aeruginosa, pyocin
      S2 DNase-ImS2 and pyocin AP41 DNase-ImAP41. These structures represent divergent
      DNase-Im subfamilies and are important in extending our understanding of protein
      protein interactions for this important class of high-affinity protein complex. A
      key finding of this work is that mutations within the immunity protein binding
      energy hotspot, helix III, are tolerated by complementary substitutions at the
      DNase-Immunity protein binding interface. Im helix III is strictly conserved in
      colicins where an Asp forms polar interactions with the DNase backbone. ImAP41
      contains an Asp-to-Gly substitution in helix III and our structures show the role
      of a co-evolved substitution where Pro in DNase loop 4 occupies the volume
      vacated and removes the unfulfilled hydrogen bond. We observe the co-evolved
      mutations in other DNase-Immunity pairs that appear to underpin the split of this
      family into two distinct groups. 

PMID- 26215616
TI  - Restless legs syndrome-current therapies and management of augmentation.
AB  - Idiopathic restless legs syndrome (RLS) can severely affect quality of life and
      disturb sleep, so that pharmacological treatment is necessary, especially for
      elderly patients. Treatment guidelines recommend initiation of therapy with
      dopamine agonists (pramipexole, ropinirole or the rotigotine transdermal patch,
      all approved in most countries) or alpha-2-delta ligands (gabapentin enacarbil,
      approved in the USA and Japan), depending on the country and availability. Where
      approved, opioids (prolonged release oxycodone-naloxone, approved in Europe) are
      also recommended as a second-line therapy for severe RLS. Several iron
      formulations can be effective but are not yet approved for RLS therapy, whereas
      benzodiazepines and other anticonvulsants are not recommended or approved. Less
      is known about effective management of RLS that is associated with other
      conditions, such as uraemia or pregnancy. Furthermore, very little data are
      available on the management of RLS when first-line treatment fails or patients
      experience augmentation. In this Review, we summarize state-of-the-art therapies
      for RLS in the context of the diagnostic criteria and available guidelines, based
      on knowledge ranging from Class I evidence for the treatment of idiopathic RLS to
      Class IV evidence for the treatment of complications such as augmentation. We
      consider therapies, including combination therapies, that are used in clinical
      practice for long-term management of RLS, despite a lack of trials and approval,
      and highlight the need for practical long-term evaluation of current trials. 

PMID- 26215622
TI  - Parkinson disease: Depression-risk factor or early symptom in Parkinson disease?

PMID- 26215625
TI  - Alzheimer disease: Cerebrospinal fluid markers for AD change during middle age.

PMID- 26215621
TI  - Lyme neuroborreliosis-epidemiology, diagnosis and management.
AB  - Lyme disease, caused by the Borrelia burgdorferi bacterium, is the most common
      vector-borne disease in the northern hemisphere. The clinical presentation varies
      with disease stage, and neurological manifestations (often referred to as Lyme
      neuroborreliosis) are reported in up to 12% of patients with Lyme disease. Most
      aspects of the epidemiology, clinical manifestation and treatment of Lyme
      neuroborreliosis are well known and accepted; only the management of so-called
      chronic Lyme disease is surrounded by considerable controversy. This term is used
      for disparate patient groups, including those who have untreated late-stage
      infection (for example, late neuroborreliosis), those with subjective symptoms
      that persist after treatment (termed 'post-treatment Lyme disease syndrome'
      [PTLDS]), and those with unexplained subjective complaints that may or may not be
      accompanied by positive test results for B. burgdorferi infection in serum (here
      called 'chronic Lyme disease'). The incidence of PTLDS is still a matter of
      debate, and its pathogenesis is unclear, but there is evidence that these
      patients do not have ongoing B. burgdorferi infection and, thus, do not benefit
      from additional antibiotic therapy. Chronic Lyme disease lacks an accepted
      clinical definition, and most patients who receive this diagnosis have other
      illnesses. Thus, a careful diagnostic work-up is needed to ensure proper
      treatment. 

PMID- 26215627
TI  - Stroke: Poststroke cognitive impairment-what are we measuring?

PMID- 26215628
TI  - [Hybrid and uncemented hip arthroplasty: Contribution margin in the German lump
      sum reimbursement system].
AB  - BACKGROUND: The economization of inpatient care began when lump sum reimbursement
      was introduced into the hospital sector. Since then, total hip arthroplasty (THA)
      has experienced a rapid development in terms of annual procedures and the
      optimization of the clinical pathway. Therefore, it is obvious to highlight THA
      as one of the most common procedures in the German health care system. In this
      work, the two most common techniques for the fixation of THA are investigated
      with regard to their cost structure and their influence on the clinical result.
      OBJECTIVES: In Germany, uncemented and hybrid fixation are used for THA. In this
      study we investigated the differences in material costs, the duration of surgery,
      and the length of stay. MATERIALS AND METHODS: For each fixation technique a
      retrospective cost analysis was carried out, based on the data from the treatment
      documentation of the University Hospital for Orthopedics, Rostock (OUK). The mean
      values of the parameters and expenses have been reviewed with descriptive
      statistics for differences. RESULTS: With regard to total costs and the
      contribution margin there was no statistically significant difference.
      CONCLUSIONS: Although there are differences in individual cost areas, in total
      costs, cost advantages and disadvantages cancel each other out. Thus, from an
      economic perspective no particular technique can be recommended.

PMID- 26215629
TI  - Leiomyomatosis peritonealis disseminata associated with appendiceal
      endometriosis: a case report.
AB  - INTRODUCTION: Leiomyomatosis peritonealis disseminata is a very rare benign
      condition of the peritoneal cavity that may mimic peritoneal carcinomatosis or
      metastatic leiomyosarcomas. It mainly develops in association with pregnancy, but
      is also rarely associated with endometriosis. CASE PRESENTATION: A 31-year-old
      Asian woman presented to our hospital with abdominal pain in the right lower
      quadrant. Her abdominopelvic computed tomography scan showed a 1.2cm-sized nodule
      at the appendiceal tip, but no other abnormal findings. We suspected acute
      appendicitis and performed an exploratory laparoscopy. Her appendix was enlarged
      at the tip portion. Also noted were blood-colored fluid collections in her pelvic
      cavity and bilateral ovarian cysts. Additionally, several small whitish firm
      solid nodules, ranging from 0.5 to 1.0cm in size, were present on her pelvic
      peritoneum. Her histological examination confirmed that the endometriosis of her
      appendix coexisted with leiomyomatosis peritonealis disseminata. CONCLUSIONS: We
      report a case involving a 31-year-old woman with acute symptoms of endometriosis
      of the appendix associated with leiomyomatosis peritonealis disseminata.
      Appendiceal endometriosis with leiomyomatosis peritonealis disseminata presenting
      as acute appendicitis is extremely rare. To the best of our knowledge, this is
      the first such case reported in the literature.

PMID- 26215630
TI  - Effects of Natural Osmolytes on the Protein Structure in Supercritical CO2:
      Molecular Level Evidence.
AB  - Protein instability in supercritical CO2 limits the application of this green
      solvent in enzyme-catalyzed reactions. CO2 molecules act as a protein denaturant
      at high pressure under supercritical conditions. Here, for the first time, we
      show that natural osmolytes could stabilize protein conformation in supercritical
      CO2. Molecular dynamics simulation is used to monitor the effects of adding
      different natural osmolytes on the conformation and dynamics of chymotrypsin
      inhibitor 2 (CI2) in supercritical CO2. Simulations showed that CI2 is denatured
      at 200 bar in supercritical CO2, which is in agreement with experimental
      observations. Interestingly, the protein conformation remains native after
      addition of ~1 M amino acid- and sugar-based osmolyte models. These molecules
      stabilize protein through the formation of supramolecular self-assemblies
      resulting from macromolecule-osmolyte hydrogen bonds. Nevertheless,
      trimethylamine N-oxide, which is known as a potent osmolyte for protein
      stabilization in aqueous solutions, amplifies protein denaturation in
      supercritical CO2. On the basis of our structural analysis, we introduce a new
      mechanism for the osmolyte effect in supercritical CO2, an "inclusion mechanism".
      To the best of our knowledge, this is the first study that introduces the
      application of natural osmolytes in a supercritical fluid and describes
      mechanistic insights into osmolyte action in nonaqueous media. 

PMID- 26215631
TI  - Myositis ossificans circumscripta.

PMID- 26215632
TI  - Heterotopic ossification.

PMID- 26215633
TI  - Cytokines and Postoperative Delirium in Older Patients Undergoing Major Elective
      Surgery.
AB  - BACKGROUND: A proinflammatory state has been associated with several age
      associated conditions; however, the inflammatory mechanisms of delirium remain
      poorly characterized. METHODS: Using the Successful Aging after Elective Surgery
      Study of adults age >=70 undergoing major noncardiac surgery, 12 cytokines were
      measured at four timepoints: preoperative, postanesthesia care unit,
      postoperative day 2 (POD2) and 30 days later (POD1M). We conducted a nested,
      longitudinal matched (on age, sex, surgery type, baseline cognition, vascular
      comorbidity, and Apolipoprotein E genotype) case-control study: delirium cases
      and no-delirium controls were selected from the overall cohort (N = 566; 24%
      delirium). Analyses were independently conducted in discovery, replication, and
      pooled cohorts (39, 36, 75 matched pairs, respectively). Nonparametric signed
      rank tests evaluating differences in cytokine levels between matched pairs were
      used to identify delirium-associated cytokines. RESULTS: In the discovery and
      replication cohorts, matching variables were similar in cases and controls.
      Compared to controls, cases had (*p < .05, **p < .01) significantly higher
      interleukin-6 on POD2 in the discovery, replication, and pooled cohorts (median
      difference [pg/mL] 50.44**, 20.17*, 39.35**, respectively). In the pooled cohort,
      cases were higher than controls for interleukin-2 (0.99*, 0.77*, 1.07**, 0.73* at
      preoperative, postanesthesia care unit, POD2, POD1M, respectively), vascular
      endothelial growth factor (4.10* at POD2), and tumor necrosis factor-alpha (3.10*
      at POD1M), while cases had lower interleukin-12 at POD1M (-4.24*). CONCLUSIONS:
      In this large, well-characterized cohort assessed at multiple timepoints, we
      observed an inflammatory signature of delirium involving elevated interleukin-6
      at POD2, which may be an important disease marker for delirium. We also observed
      preliminary evidence for involvement of other cytokines.

PMID- 26215634
TI  - The pseudokinase SgK223 promotes invasion of pancreatic ductal epithelial cells
      through JAK1/Stat3 signaling.
AB  - BACKGROUND: Characterization of molecular mechanisms underpinning development of
      pancreatic ductal adenocarcinoma (PDAC) may lead to the identification of novel
      therapeutic targets and biomarkers. SgK223, also known as Pragmin, is a
      pseudokinase and scaffolding protein closely related to SgK269/PEAK1. Both
      proteins are implicated in oncogenic tyrosine kinase signaling, but their
      mechanisms and function remain poorly characterized. METHODS: Expression of
      SgK223 in PDAC and PDAC cell lines was characterized using gene expression
      microarrays, mass spectrometry (MS)-based phosphoproteomics and Western blotting.
      SgK223 was overexpressed in human pancreatic ductal epithelial (HPDE) cells via
      retroviral transduction, and knocked down in PDAC cells using siRNA. Cell
      proliferation was determined using a colorimetric cell viability assay, and cell
      migration and invasion using transwells. Expression of markers of epithelial
      mesenchyme transition (EMT) was assayed by quantitative PCR. SgK223 and Stat3
      signaling was interrogated by immunoprecipitation, Western blot and gene reporter
      assays. The functional role of specific kinases and Stat3 was determined using
      selective small molecule inhibitors. RESULTS: Elevated site-selective tyrosine
      phosphorylation of SgK223 was identified in subsets of PDAC cell lines, and
      increased expression of SgK223 detected in several PDAC cell lines compared to
      human pancreatic ductal epithelial (HPDE) cells and in PDACs compared to normal
      pancreas. Expression of SgK223 in HPDE cells at levels comparable to those in
      PDAC did not alter cell proliferation but led to a more elongated morphology,
      enhanced migration and invasion and induced gene expression changes
      characteristic of a partial EMT. While SgK223 overexpression did not affect
      activation of Erk or Akt, it led to increased Stat3 Tyr705 phosphorylation and
      Stat3 transcriptional activity, and SgK223 and Stat3 associated in vivo. SgK223
      overexpressing cells exhibited increased JAK1 activation, and use of selective
      inhibitors determined that the increased Stat3 signaling driven by SgK223 was JAK
      dependent. Pharmacological inhibition of Stat3 revealed that Stat3 activation was
      required for the enhanced motility and invasion of SgK223-overexpressing cells.
      CONCLUSIONS: Increased expression of SgK223 occurs in PDAC, and overexpression of
      SgK223 in pancreatic ductal epithelial cells promotes acquisition of a migratory
      and invasive phenotype through enhanced JAK1/Stat3 signaling. This represents the
      first association of SgK223 with a particular human cancer, and links SgK223 with
      a major signaling pathway strongly implicated in PDAC progression.

PMID- 26215635
TI  - Direct epoxidation of propylene over stabilized Cu(+) surface sites on titanium
      modified Cu2O.
AB  - Direct propylene epoxidation by O2 is a challenging reaction because of the
      strong tendency for complete combustion. Results from the current study
      demonstrate that by generating highly dispersed and stabilized Cu(+) active sites
      in a TiCuOx mixed oxide the epoxidation selectivity can be tuned. The TiCuOx
      surface anchors the key surface intermediate, an oxametallacycle, leading to
      higher selectivity for epoxidation of propylene. 

PMID- 26215636
TI  - Lipidic dispersion to reduce food dependent oral bioavailability of fenofibrate:
      In vitro, in vivo and in silico assessments.
AB  - Novel formulations that overcome the solubility limitations of poorly water
      soluble drugs (PWSD) are becoming ever more critical to a drug development
      process inundated with these compounds. There is a clear need for developing bio
      enabling formulation approaches to improve oral bioavailability for PWSD, but
      also to establish a range of predictive in vitro and in silico biopharmaceutics
      based tools for guiding formulation design and forecasting in vivo effects. The
      dual aim of this study was to examine the potential for a novel lipid based
      formulation, termed a lipidic dispersion, to enhance fasted state oral
      bioavailability of fenofibrate, while also assessing the predictive ability of
      biorelevant in vitro and in silico testing. Formulation as a lipidic dispersion
      improved both dissolution and solubilisation of fenofibrate through a combination
      of altered solid state characteristics and incorporation of solubilising lipidic
      excipients. These changes resulted in an increased rate of absorption and
      increased maximal plasma concentrations compared to a commercial, micronised
      product (Lipantil(r) Micro) in a pig model. Combination of biorelevant in vitro
      measurements with in silico physiologically based pharmacokinetic (PBPK)
      modelling resulted in an accurate prediction of formulation performance and
      forecasts a reduction in food effects on fenofibrate bioavailability through
      maximising its fasted state dissolution. 

PMID- 26215637
TI  - Risk of disability pension in patients following rectal cancer treatment and
      surgery.
AB  - BACKGROUND: Aspects of survivorship, such as long-term ability to work, are
      increasingly relevant owing to the improved survival of patients with rectal
      cancer. The aim of this study was to assess risk and determinants of disability
      pension (DP) in this patient group. METHODS: Using Swedish national clinical and
      population-based registers, patients with stage I-III rectal cancer aged 18-61
      years in 1995-2009 were identified at diagnosis and matched with population
      comparators. Prospectively registered records of DP during follow-up were
      retrieved up to 2013. Non-proportional and proportional hazards models were used
      to estimate the incidence rate ratio (IRR) for DP annually and overall. Potential
      variations in risk by demographic and clinical factors were calculated, with
      relapse as a time-varying exposure. RESULTS: A total of 2815 patients were
      identified and compared with 13 465 population comparators. During a median
      follow-up of 6.0 (range 0-10) years, 23.3 per cent of the relapse-free patients
      and 10.3 per cent of the population comparators received DP (IRR 2.40, 95 per
      cent c.i. 2.17 to 2.65). An increased annual risk of DP was evident almost every
      year until the tenth year of follow-up. Abdominoperineal resection was associated
      with an increased DP risk compared with anterior resection (IRR 1.44, 1.19 to
      1.75). Surgical complications (IRR 1.33, 1.10 to 1.62) and reoperation (IRR 1.42,
      1.09 to 1.84), but not radiotherapy or chemotherapy, were associated with risk of
      DP. CONCLUSION: Relapse-free patients with rectal cancer of working age are at
      risk of disability pension.

PMID- 26215638
TI  - FusionCancer: a database of cancer fusion genes derived from RNA-seq data.
AB  - BACKGROUND: Fusion genes are chimeric results originated from previous separate
      genes with aberrant functions. The resulting protein products may lead to
      abnormal status of expression levels, functions and action sites, which in return
      may cause the abnormal proliferation of cells and cancer development. RESULTS:
      With the emergence of next-generation sequencing technology, RNA-seq has spurred
      gene fusion discovery in various cancer types. In this work, we compiled 591
      recently published RNA-seq datasets in 15 kinds of human cancer, and the gene
      fusion events were comprehensively identified. Based on the results, a database
      was developed for gene fusion in cancers (FusionCancer), with the attempt to
      provide a user-friendly utility for the cancer research community. A flexible
      query engine has been developed for the acquisition of annotated information of
      cancer fusion genes, which would help users to determine the chimera events
      leading to functional changes. FusionCancer can be accessible at the following
      hyperlink website: http://donglab.ecnu.edu.cn/databases/FusionCancer/ CONCLUSION:
      To the best of our knowledge, FusionCancer is the first comprehensive fusion gene
      database derived only from cancer RNA-seq data.

PMID- 26215639
TI  - Molecular basis and drug sensitivity of the delayed rectifier (IKr) in the fish
      heart.
AB  - Fishes are increasingly used as models for human cardiac diseases, creating a
      need for a better understanding of the molecular basis of fish cardiac ion
      currents. To this end we cloned KCNH6 channel of the crucian carp (Carassius
      carassius) that produces the rapid component of the delayed rectifier K(+)
      current (IKr), the main repolarising current of the fish heart. KCNH6 (ccErg2)
      was the main isoform of the Kv11 potassium channel family with relative
      transcript levels of 98.9% and 99.6% in crucian carp atrium and ventricle,
      respectively. KCNH2 (ccErg1), an orthologue to human cardiac Erg (Herg) channel,
      was only slightly expressed in the crucian carp heart. The native atrial IKr and
      the cloned ccErg2 were inhibited by similar concentrations of verapamil,
      terfenadine and KB-R7943 (P>0.05), while the atrial IKr was about an order of
      magnitude more sensitive to E-4031 than ccErg2 (P<0.05) suggesting that some
      accessory beta-subunits may be involved. Sensitivity of the crucian carp atrial
      IKr to E-4031, terfenadine and KB-R7943 was similar to what has been reported for
      the Herg channel. In contrast, the sensitivity of the crucian carp IKr to
      verapamil was approximately 30 times higher than the previously reported values
      for the Herg current. In conclusion, the cardiac IKr is produced by non
      orthologous gene products in fish (Erg2) and mammalian hearts (Erg1) and some
      marked differences exist in drug sensitivity between fish and mammalian Erg1/2
      which need to be taken into account when using fish heart as a model for human
      heart. 

PMID- 26215640
TI  - Short-term exposure to L-type calcium channel blocker, verapamil, alters the
      expression pattern of calcium-binding proteins in the brain of goldfish,
      Carassius auratus.
AB  - The influx of calcium ions (Ca(2+)) is responsible for various physiological
      events including neurotransmitter release and synaptic modulation. The L-type
      voltage dependent calcium channels (L-type VDCCs) transport Ca(2+) across the
      membrane. Calcium-binding proteins (CaBPs) bind free cytosolic Ca(2+) and prevent
      excitotoxicity caused by sudden increase in cytoplasmic Ca(2+). The present study
      was aimed to understand the regulation of expression of neuronal CaBPs, namely,
      calretinin (CR) and parvalbumin (PV) following blockade of L-type VDCCs in the
      CNS of Carassius auratus. Verapamil (VRP), a potent L-type VDCC blocker,
      selectively blocks Ca(2+) entry at the plasma membrane level. VRP present in the
      aquatic environment at a very low residual concentration has shown
      ecotoxicological effects on aquatic animals. Following acute exposure for 96h,
      median lethal concentration (LC50) for VRP was found to be 1.22mg/L for goldfish.
      At various doses of VRP, the behavioral alterations were observed in the form of
      respiratory difficulty and loss of body balance confirming the cardiovascular
      toxicity caused by VRP at higher doses. In addition to affecting the
      cardiovascular system, VRP also showed effects on the nervous system in the form
      of altered expression of PV. When compared with controls, the pattern of CR
      expression did not show any variations, while PV expression showed significant
      alterations in few neuronal populations such as the pretectal nucleus, inferior
      lobes, and the rostral corpus cerebellum. Our result suggests possible regulatory
      effect of calcium channel blockers on the expression of PV. 

PMID- 26215641
TI  - Relationship between activation of ankle muscles and quasi-joint stiffness in
      early and middle stances during gait in patients with hemiparesis.
AB  - It is unclear whether muscle contraction is necessary to increase quasi-joint
      stiffness (QJS) of the ankle joint during gait in patients with hemiparesis. The
      purpose of the present study was to investigate the relationship between QJS and
      muscle activation at the ankle joint in the stance phase during gait in patients
      with hemiparesis. Spatiotemporal and kinetic gait parameters and activation of
      the medial head of the gastrocnemius (MG), soleus (SOL), and tibialis anterior
      (TA) muscles were measured using a 3-dimensional motion analysis system and
      surface electromyography, in 21 patients with hemiparesis due to stroke and 10
      healthy individuals. In the early stance, the QJS on the paretic side (PS) of
      patients was greater than that on the non-PS (p<0.05) and not significantly
      correlated with activation of the three muscles. In the middle stance, the QJS on
      the PS was lower than that on the non-PS (p<0.05) and that on the right side of
      controls (p<0.001), which was positively correlated with activation of the MG
      (r=0.51, p<0.05) and SOL (r=0.49, p<0.05). In the patients with hemiparesis,
      plantarflexor activation may not contribute to QJS in the early stance. On the
      other hand, QJS in the middle stance may be attributed to activation of the MG
      and SOL. Our findings suggest that activation of the MG and SOL in the middle
      stance on the PS may require to be enhanced to increase QJS during gait in
      patients with hemiparesis. 

PMID- 26215642
TI  - On the implementation of predictive methods to locate the hip joint centres.
AB  - The purpose of this short communication is to discuss the relative benefits of
      various anthropometric parameters to drive predictive equations to locate the hip
      joint centres. The effect of soft tissue thickness over the anterior and
      posterior superior iliac spines on pelvic depth, pelvic width and leg length and
      position of the hip joint centres was discussed theoretically and experimentally,
      from a secondary analysis of previously published data. Results highlighted that
      anthropometric measurements of pelvic width and leg length were similar when
      obtained from MRI images or during gait analysis whereas pelvic depth was
      different. The secondary analysis showed that Harrington et al. [5] equations
      using either only pelvic width or only leg length would lead to 3mm improvement,
      in average over 164 limbs, over the equations using the best anthropometric
      predictors from MRI data. 

PMID- 26215643
TI  - Urinary phosphorus excretion per creatinine clearance as a prognostic marker for
      progression of chronic kidney disease: a retrospective cohort study.
AB  - BACKGROUND: Whether phosphate itself has nephrotoxicity in patients with chronic
      kidney disease (CKD) is controversial, although phosphate excretion into urine
      may cause tubular damage in rat models. To evaluate actual phosphate load on each
      nephron, we examined the association between 24-h urinary phosphorus excretion
      per creatinine clearance (24-h U-P/CCr), a newly proposed index that is a
      surrogate for nephron load, and CKD progression in patients with CKD. METHODS: We
      conducted a single-center, retrospective cohort study. To avoid potential
      confounders for protein intake, only patients on our educational program for CKD
      with a fixed diet regimen and aged 20 years or older were included. The
      observation period was 3 years. Primary outcomes were CKD progression defined as
      a composite of end-stage kidney disease (ESKD) or 50 % reduction of estimated
      glomerular filtration rate. Patients were stratified by quartiles of 24-h U-P/CCr
      levels as Quartiles 1-4. The association was examined in three models: unadjusted
      (Model 1), adjusted for risk factors for CKD progression (Model 2), and factors
      that affect renal phosphate handling (Model 3). RESULTS: A total of 191 patients
      met the eligibility criteria. Patients with higher 24-h U-P/CCr showed a higher
      risk for the composite outcomes. The hazard ratios [95 % confidence interval] for
      24-h U-P/CCr levels in Quartile 2, 3, and 4, respectively, versus Quartile 1 were
      2.56 (1.15-6.24), 7.53 (3.63-17.62), and 12.17 (5.82-28.64) in Model 1; 1.66
      (0.63-4.97), 3.57 (1.25-11.71), and 5.34 (1.41-22.32) in Model 2; and 3.07 (0.97
      11.85), 7.52 (2.13-32.69), and 7.89 (1.74-44.33) in Model 3. CONCLUSIONS: Our
      study showed that higher phosphorus excretion per creatinine clearance was
      associated with CKD progression.

PMID- 26215645
TI  - Successful removal of a foreign body from a gallbladder remnant by using a new
      single-operator digital cholangioscope.

PMID- 26215644
TI  - Municipal return to work management in cancer survivors undergoing cancer
      treatment: a protocol on a controlled intervention study.
AB  - BACKGROUND: Cancer survivors are often left on their own to deal with the
      challenges of resuming work during or after cancer treatment, mainly due to
      unclear agreements between stakeholders responsible for occupational
      rehabilitation. Social inequality exists in cancer risk, survival probability and
      continues with regard to the chance of being able to return to work. The aim is
      to apply an early, individually tailored occupational rehabilitation intervention
      to cancer survivors in two municipalities parallel with cancer treatment focusing
      on enhancing readiness for return to work. METHODS/DESIGN: In a controlled trial
      municipal job consultants use acceptance and commitment therapy dialogue and
      individual-placement-and-support-inspired tools with cancer survivors to engage
      them in behaviour changes toward readiness for return to work. The workplace is
      involved in the return to work process. Patients referred to surgery,
      radiotherapy or chemotherapy at the Oncology Department, Aarhus University
      Hospital, Denmark for the diagnoses; breast, colon-rectal, head and neck, thyroid
      gland, testicular, ovarian or cervix cancer are eligible for the study. Patients
      must be residents in the municipalities of Silkeborg or Randers, 18-60 years of
      age and have a permanent or temporary employment (with at least 6 months left of
      their contract) at inclusion. Patients, for whom the treating physician considers
      occupational rehabilitation to be unethical, or who are not reading or talking
      Danish are excluded. The control group has identical inclusion and exclusion
      criteria except for municipality of residence. Return to work is the primary
      outcome and is indentified in a social transfer payment register. Effect is
      assessed as relative cumulative incidences within 52 weeks and will be analysed
      in generalised linear regression models using the pseudo values method. As a
      secondary outcome; co-morbidity and socio-economic status is analysed as effect
      modifiers of the intervention effect on return to work. DISCUSSION: The
      innovative element of this intervention is the timing of the occupational
      rehabilitation which is much earlier initiated than usual and the active
      involvement of the workplace. We anticipate that vulnerable cancer survivors will
      benefit from this approach and reduce the effects of social inequality on
      workability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN50753764 .
      Registered August 21(st), 2014.

PMID- 26215646
TI  - EUS-guided gastroenterostomy: the first U.S. clinical experience (with video).
AB  - BACKGROUND AND AIMS: There are limitations to enteral self-expandable metal
      stents and surgical gastrojejunostomy in the treatment of patients with gastric
      outlet obstruction (GOO). EUS-guided gastroenterostomy (EUS-GE) is a novel
      procedure that potentially offers long-lasting luminal patency without the risk
      of tumor ingrowth and/or overgrowth, while avoiding the morbidity of a surgical
      procedure. The aims of this study were to report the first U.S. clinical
      experience with EUS-GE in terms of technical success, clinical success, and
      adverse events and to detail the technical aspects of performing EUS-GE. METHODS:
      This was a retrospective study from two tertiary-care centers. EUS-GE was
      performed by using either the direct EUS-GE or balloon-assisted EUS-GE technique.
      Technical success was defined as adequate positioning and deployment of the stent
      as determined endoscopically and radiologically. Clinical success was defined as
      the patient's ability to tolerate oral intake without vomiting. RESULTS: A total
      of 10 patients underwent attempted EUS-GE. Malignant GOO was present in 3
      patients, whereas benign obstruction was found in the remaining 7. One patient
      had complete GOO and underwent successful direct EUS-GE. In the remaining 9
      patients, balloon-assisted EUS-GE was attempted and was successful in 8. Thus,
      technical success occurred in 9 patients (90%). There were no procedure-related
      adverse events. Mean procedure time was 96 minutes (range 45-152 minutes), and
      mean length of hospital stay was 2.2 days. Clinical success with resumption of
      solid oral intake was achieved in all 9 patients (100%) who underwent successful
      EUS-GE. A total of 8 patients were able to tolerate almost a normal diet and/or
      full diet, and 1 patient tolerated a soft diet. There was no symptom recurrence
      during a mean follow-up period of 150 days. CONCLUSIONS: EUS-GE is a promising
      new technique for the treatment of symptoms of benign and malignant GOO.
      Prospective, multicenter trials are needed to confirm these results.

PMID- 26215647
TI  - Endoscopic reversal of Roux-en-Y gastric bypass.

PMID- 26215648
TI  - Biliary drainage: role of EUS guidance.
AB  - BACKGROUND AND AIMS: EUS-guided biliary drainage is a technique being
      increasingly used when ERCP fails, and it has been the focus of multiple studies
      and investment in recent years. However, the proportion of cases for which it is
      really indicated has not been established. The aim of this study is to determine
      how often EUS-guided biliary drainage is needed in a tertiary-care level
      therapeutic endoscopy unit. METHODS: This is a prospective cohort study at a
      single tertiary-care center with a high volume of therapeutic endoscopy. A
      thousand consecutive ERCPs performed from November 1, 2013 to September 12, 2014
      were screened, and those with previous biliary intervention were excluded (n =
      476). EUS-guided biliary drainage was performed in suitable patients with failed
      ERCP and malignant biliary obstruction. The main outcome measures were the rates
      of ERCP failure and EUS-guided biliary drainage. RESULTS: A total of 524 native
      papilla ERCPs were performed (41.2% male; median age 60 years, range 6-97 years;
      9.4% outside failed ERCP; 1.9% surgically altered anatomy). The ampulla was
      reached in 518 (98.9%) and not reached in 6 (1.1%) because of surgically altered
      anatomy (n = 2), malignant duodenal stenosis (n = 3), or both (n = 1). The
      overall ERCP failure rate was 1.7% (9/524). Cannulation was successful in 99.4%
      (515/518) and unsuccessful in 0.6% (3/518) of cases in which the ampulla was
      reached. EUS-guided biliary drainage was indicated in 0.6% (3/524) of all
      referred native papilla ERCPs, or 33% (3/9) of those patients with failed ERCP;
      EUS-biliary drainage was successful in all cases. CONCLUSIONS: In a tertiary-care
      center, use of advanced ERCP techniques results in a high technical success rate.
      EUS-guided biliary drainage was required in only 0.6% of native papilla ERCPs,
      and although a number of excellent indications exist, it should not replace good
      ERCP technique.

PMID- 26215649
TI  - Endoscopic submucosal dissection of ectopic pancreas with pancreatitis and
      pseudocyst formation.

PMID- 26215650
TI  - The CHANGE Study: Methods and Sample Description for a Cross-Sectional Study of
      Heroin Cessation in New York City.
AB  - The CHANGE (Cessation of Heroin: A Neighborhood Grounded Exploration) Study aimed
      to understand factors associated with the initiation and maintenance of sustained
      heroin cessation from the perspective of users themselves and specifically set
      out to document the correlates of natural recovery. The CHANGE Study was a case
      control study conducted in New York City from 2009 to 2011. Cases were former
      heroin users, abstinent for 1-5 years in the past 5 years. Controls used heroin
      at least weekly during the past 5 years and were (1) continuous heroin users
      without a quit attempt of >=2 weeks' duration or (2) relapsed heroin users who
      were currently using and had a quit attempt of >=2 weeks' duration during the
      past 5 years. Recruitment and data collection methods are described along with
      limitations and a brief description of the study sample. In contrast to many
      studies of drug use and cessation, the CHANGE Study was designed to model success
      (i.e., initiation and maintenance of heroin cessation) and not failure.

PMID- 26215652
TI  - Role of the immune system and inflammation in ionizing radiation effects.

PMID- 26215651
TI  - Details of development of the resource for adults with asthma in the RAISIN
      (randomized trial of an asthma internet self-management intervention) study.
AB  - BACKGROUND: Around 300 million people worldwide have asthma and prevalence is
      increasing. Self-management can be effective in improving a range of outcomes and
      is cost effective, but is underutilised as a treatment strategy. Supporting
      optimum self-management using digital technology shows promise, but how best to
      do this is not clear. We aimed to develop an evidence based, theory informed,
      online resource to support self-management in adults with asthma, called 'Living
      well with Asthma', as part of the RAISIN (Randomized Trial of an Asthma Internet
      Self-Management Intervention) study. METHODS: We developed Living well with
      Asthma in two phases. Phase 1: A low fidelity prototype (paper-based) version of
      the website was developed iteratively through input from a multidisciplinary
      expert panel, empirical evidence from the literature, and potential end users via
      focus groups (adults with asthma and practice nurses). Implementation and
      behaviour change theories informed this process. Phase 2: The paper-based designs
      were converted to a website through an iterative user centred process. Adults
      with asthma (n = 10) took part in think aloud studies, discussing the paper based
      version, then the web-based version. Participants considered contents, layout,
      and navigation. Development was agile using feedback from the think aloud
      sessions immediately to inform design and subsequent think aloud sessions. Think
      aloud transcripts were also thematically analysed, further informing resource
      development. RESULTS: The website asked users to aim to be symptom free. Key
      behaviours targeted to achieve this include: optimising medication use (including
      inhaler technique); attending primary care asthma reviews; using asthma action
      plans; increasing physical activity levels; and stopping smoking. The website had
      11 sections, plus email reminders, which promoted these behaviours. Feedback on
      the contents of the resource was mainly positive with most changes focussing on
      clarification of language, order of pages and usability issues mainly relating to
      navigation difficulties. CONCLUSIONS: Our multifaceted approach to online
      intervention development underpinned by theory, using evidence from the
      literature, co-designed with end users and a multidisciplinary panel has resulted
      in a resource which end users find relevant to their needs and easy to use.
      Living well with Asthma is undergoing evaluation within a randomized controlled
      trial.

PMID- 26215653
TI  - Autoregressive spectral analysis of cortical electroencephalographic signals in a
      rat model of post-traumatic epilepsy.
AB  - OBJECTIVES: Post-traumatic epilepsy (PTE) is a common consequence of traumatic
      brain injury (TBI) and significant predictor of poor prognosis in TBI patients.
      To develop clinical interventions for PTE risk reduction, there is a need to
      elucidate the epileptogenic mechanisms induced by brain injury. METHODS: The iron
      induced rat model of epilepsy used here mimics many aspects of human PTE.
      Intracortical injection of iron results in local neuronal damage and the
      establishment of an epileptic focus, leading to chronic spontaneous
      electroencephalographic (EEG) signals and motor seizures, with progressively
      increasing frequency over many months. Identifying unique aspects of PTE seizure
      semiology for prognosis and treatment may be aided by novel methods of EEG
      analysis. Here, autoregressive (AR) methods were compared to the conventional
      fast Fourier transform (FFT) for processing EEG signals in iron-induced epilepsy.
      RESULTS: Power spectra obtained using AR showed higher frequency resolution over
      a given epoch than the spectra obtained using FFT. Moreover, changes in total AR
      spectral power and frequency distribution over brief successive periods provided
      convenient indexes for long-term monitoring of seizures. DISCUSSION:
      Autoregression analysis may prove complementary to FFT for EEG analysis in PTE
      patients.

PMID- 26215654
TI  - Occupational contact dermatitis caused by nickel in scratchcards.

PMID- 26215655
TI  - Monitoring the sensory quality of canned white asparagus through cluster
      analysis.
AB  - BACKGROUND: White asparagus is one of the 30 vegetables most consumed in the
      world. This paper unifies the stages of their sensory quality control. The aims
      of this work were to describe the sensory properties of canned white asparagus
      and their quality control and to evaluate the applicability of agglomerative
      hierarchical clustering (AHC) for classifying and monitoring the sensory quality
      of manufacturers. RESULTS: Sixteen sensory descriptors and their evaluation
      technique were defined. The sensory profile of canned white asparagus was high
      flavor characteristic, little acidity and bitterness, medium firmness and very
      light fibrosity, among other characteristics. The dendrogram established groups
      of manufacturers that had similar scores in the same set of descriptors, and each
      cluster grouped the manufacturers that had a similar quality profile. CONCLUSION:
      The sensory profile of canned white asparagus was clearly defined through the
      intensity evaluation of 16 descriptors, and the sensory quality report provided
      to the manufacturers is in detail and of easy interpretation. AHC grouped the
      manufacturers according to the highest quality scores in certain descriptors and
      is a useful tool because it is very visual. (c) 2015 Society of Chemical
      Industry.

PMID- 26215656
TI  - The Phytoene synthase gene family of apple (Malus x domestica) and its role in
      controlling fruit carotenoid content.
AB  - BACKGROUND: Carotenoid compounds play essential roles in plants such as
      protecting the photosynthetic apparatus and in hormone signalling. Coloured
      carotenoids provide yellow, orange and red colour to plant tissues, as well as
      offering nutritional benefit to humans and animals. The enzyme phytoene synthase
      (PSY) catalyses the first committed step of the carotenoid biosynthetic pathway
      and has been associated with control of pathway flux. We characterised four PSY
      genes found in the apple genome to further understand their involvement in fruit
      carotenoid accumulation. RESULTS: The apple PSY gene family, containing six
      members, was predicted to have three functional members, PSY1, PSY2, and PSY4,
      based on translation of the predicted gene sequences and/or corresponding cDNAs.
      However, only PSY1 and PSY2 showed activity in a complementation assay. Protein
      localisation experiments revealed differential localization of the PSY proteins
      in chloroplasts; PSY1 and PSY2 localized to the thylakoid membranes, while PSY4
      localized to plastoglobuli. Transcript levels in 'Granny Smith' and 'Royal Gala'
      apple cultivars showed PSY2 was most highly expressed in fruit and other
      vegetative tissues. We tested the transient activation of the apple PSY1 and PSY2
      promoters and identified potential and differential regulation by AP2/ERF
      transcription factors, which suggested that the PSY genes are controlled by
      different transcriptional mechanisms. CONCLUSION: The first committed carotenoid
      pathway step in apple is controlled by MdPSY1 and MdPSY2, while MdPSY4 play
      little or no role in this respect. This has implications for apple breeding
      programmes where carotenoid enhancement is a target and would allow co
      segregation with phenotypes to be tested during the development of new cultivars.

PMID- 26215657
TI  - A composite likelihood approach for estimating HIV prevalence in the presence of
      spatial variation.
AB  - Since 1990, the World Health Organization has recommended HIV surveillance among
      pregnant women as an essential surveillance activity for countries with
      generalized HIV epidemics. Despite the widespread availability and potential
      usefulness of antenatal HIV surveillance, analyses of such data present important
      challenges. Within an individual clinic, the HIV status of its attendees may be
      correlated because of similarities in HIV risk among women close in age. Between
      clinic correlation may also arise as women often seek antenatal care at clinics
      located close to their home, and individuals living in nearby communities may
      share important characteristics or behaviours related to susceptibility. A
      general estimating equation-based approach for spatially-correlated, binary data
      such as that antenatal HIV surveillance based on a pairwise composite likelihood
      has been described. We present an extended version of this model that can
      accommodate penalized spline estimators and apply it to antenatal HIV
      surveillance data collected in 2011 in Botswana to estimate the effects of
      proximity to the 'hotspot' of the country's HIV epidemic and age on HIV
      prevalence. Finally, we compare the results with a logistic regression analysis,
      which ignores potential correlation of responses.

PMID- 26215658
TI  - Role of Ryanodine and NMDA Receptors in Tetrabromobisphenol A-Induced Calcium
      Imbalance and Cytotoxicity in Primary Cultures of Rat Cerebellar Granule Cells.
AB  - The study assessed the role of ryanodine receptors (RyRs) and NMDA receptors
      (NMDARs) in the Ca(2+) transients and cytotoxicity induced in neurons by the
      brominated flame retardant tetrabromobisphenol A (TBBPA). Primary cultures of rat
      cerebellar granule cells (CGC) were exposed to 7.5, 10, or 25 uM TBBPA for 30
      min, and cell viability was assessed after 24 h. Moreover, (45)Ca uptake was
      measured, and changes in the intracellular Ca(2+) concentration ([Ca(2+)]i) were
      studied using the fluo-3 probe. The involvement of NMDARs and RyRs was verified
      using the pertinent receptor antagonists, 0.5 uM MK-801 and 2.5 uM bastadin 12,
      which was co-applied with 200 uM ryanodine, respectively. The results show that
      TBBPA concentration-dependently induces an increase in [Ca(2+)]i. This effect was
      partly suppressed by the inhibitors of RyRs and NMDARs when administered
      separately, and completely abrogated by their combined application. A
      concentration-dependent activation of (45)Ca uptake by TBBPA was prevented by MK
      801 but not by RyR inhibitors. Application of >= 10 uM TBBPA concentration
      dependently reduced neuronal viability, and this effect was only partially and to
      an equal degree reduced by NMDAR and RyR antagonists given either separately or
      in combination. Our results directly demonstrate that both the RyR-mediated
      release of intracellular Ca(2+) and the NMDAR-mediated influx of Ca(2+) into
      neurons participate in the mechanism of TBBPA-induced Ca(2+) imbalance in CGC and
      play a significant, albeit not exclusive, role in the mechanisms of TBBPA
      cytotoxicity.

PMID- 26215660
TI  - Major Lung Resections Using Manual Suturing Versus Staplers During Fiscal Crisis.
AB  - : AbstractObjective: During fiscal crisis there was a period of shortage of
      staplers in our hospital, which drove us to manual suturing of bronchi and
      pulmonary vessels during major lung resections. We present our experience during
      that period in comparison to a subsequent period when staplers became available
      again. METHODS: A total of 256 lobectomies and 78 pneumonectomies were performed
      using manual suturing (group A), between September 2009 and September 2010, and
      compared regarding surgical outcome to 248 lobectomies and 60 pneumonectomies
      using staplers (group B), between September 2011 and September 2012. RESULTS:
      Although we did not observe statistically significant differences but only a
      trend towards less operative time, for both lobectomies (p=0.21) and
      pneumonectomies (p=0.31), we actually noted a 41 and 47 minutes saving of
      operative time using staplers (group B), in comparison to manual suturing (group
      A). We also observed a trend towards less morbidity rates in patients of group B,
      who underwent lobectomy (10.48%), and pneumonectomy (20%), versus patients of
      group A, who underwent lobectomy (15.62%), and pneumonectomy (30.76%); we did not
      observe any substantial differences in the other surgical outcome variables, and
      in patients' demographics comorbidities, and anatomic allocation of surgical
      procedures performed. CONCLUSIONS: The use of staplers offers safety with secure
      bronchial or vascular sealing, and saving of operative time. Their unavailability
      at an interval during fiscal crisis although it did not affect surgical outcome,
      revealed their usefulness and value.

PMID- 26215659
TI  - Histamine resets the circadian clock in the suprachiasmatic nucleus through the
      H1R-CaV 1.3-RyR pathway in the mouse.
AB  - Histamine, a neurotransmitter/neuromodulator implicated in the control of arousal
      state, exerts a potent phase-shifting effect on the circadian clock in the rodent
      suprachiasmatic nucleus (SCN). In this study, the mechanisms by which histamine
      resets the circadian clock in the mouse SCN were investigated. As a first step,
      Ca(2+) -imaging techniques were used to demonstrate that histamine increases
      intracellular Ca(2+) concentration ([Ca(2+) ]i ) in acutely dissociated SCN
      neurons and that this increase is blocked by the H1 histamine receptor (H1R)
      antagonist pyrilamine, the removal of extracellular Ca(2+) and the L-type Ca(2+)
      channel blocker nimodipine. The histamine-induced Ca(2+) transient is reduced,
      but not blocked, by application of the ryanodine receptor (RyR) blocker
      dantrolene. Immunohistochemical techniques indicated that CaV 1.3 L-type Ca(2+)
      channels are expressed mainly in the somata of SCN cells along with the H1R,
      whereas CaV 1.2 channels are located primarily in the processes. Finally,
      extracellular single-unit recordings demonstrated that the histamine-elicited
      phase delay of the circadian neural activity rhythm recorded from SCN slices is
      blocked by pyrilamine, nimodipine and the knockout of CaV 1.3 channel. Again,
      application of dantrolene reduced but did not block the histamine-induced phase
      delays. Collectively, these results indicate that, to reset the circadian clock,
      histamine increases [Ca(2+) ]i in SCN neurons by activating CaV 1.3 channels
      through H1R, and secondarily by causing Ca(2+) -induced Ca(2+) release from RyR
      mediated internal stores. 

PMID- 26215661
TI  - Centrifugal microfluidic platform for single-cell level cardiomyocyte-based drug
      profiling and screening.
AB  - Drug screening and profiling is an important phase in drug discovery,
      development, and marketing. However, some profiling tests are not routinely done
      because of the needed additional technical skills and costly maintenance, which
      leads to cases of unexpected side effects or adverse drug reactions (ADRs). This
      study presents the design and operation of a microfluidic chip for single-cell
      level drug screening and profiling as an alternative platform for this purpose.
      Centrifugation was utilized to trap isolated single and groups of primary
      cultured neonatal rat cardiomyocytes in the same chip. In the off-spin operation
      of the chip, the cells can be observed under a microscope and movies of the beat
      motion can be recorded. The beat profiles of the cells were generated by image
      correlation analysis of the recorded video to study the contractile
      characteristics (beating rate, beating strength, and inter-beat duration). By
      utilizing this non-invasive tool, long term continuous monitoring, right after
      trapping, was made possible and cell growth and dynamics were successfully
      observed in the chip. Media and liquid replacement does not require further
      centrifugation but instead utilizes capillary flow only. The effect of carbachol
      (100 MUM) and isoproterenol (4 MUg mL(-1)) on single cells and groups of cells
      was demonstrated and the feature for immunostaining (beta-actin) applicability of
      the chip was revealed. Furthermore, these findings can be helpful for the headway
      of non-invasive profiling of cardiomyocytes and for future chip design and
      operation of high-throughput lab-on-a-chip devices. 

PMID- 26215662
TI  - Asymptomatic Brugada Syndrome: Clinical Characterization and Long-Term Prognosis.
AB  - BACKGROUND: Among Brugada syndrome patients, asymptomatic individuals are
      considered to be at the lowest risk. Nevertheless, arrhythmic events and sudden
      cardiac death are not negligible. Literature focused on this specific group of
      patients is sparse. The purpose of this study is to investigate the clinical
      characteristics, management, and long-term prognosis of asymptomatic Brugada
      syndrome patients. METHODS AND RESULTS: Patients presenting with spontaneous or
      drug-induced Brugada type I ECG and no symptoms at our institution were
      considered eligible. A total of 363 consecutive patients (200 men, 55.1%; mean
      age, 40.9+/-17.2 years; 41 [11.3%] with spontaneous type I ECG) were included.
      Electrophysiological study was performed in 321 (88.4%) patients, and ventricular
      arrhythmias were induced in 32 (10%) patients. An implantable cardioverter
      defibrillator was implanted in 61 (16.8%) patients. After a mean follow-up time
      of 73.2+/-58.9 months, 9 arrhythmic events occurred, accounting for an annual
      incidence rate of 0.5%. Event-free survival was 99.0% at 1 year, 96.2% at 5
      years, and 95.4% at 10 and 15 years. Univariate analysis identified as risk
      factors: electrophysiological study inducibility (hazard ratio, 11.4; P<0.01),
      spontaneous type I (hazard ratio, 4.0; P=0.04), and previous sinus node
      dysfunction (hazard ratio, 8.0; 95% confidence interval, 1.0-63.9; P=0.05). At
      the multivariate analysis, only inducibility remained significant (hazard ratio,
      9.1; P<0.01). CONCLUSIONS: Arrhythmic events in asymptomatic Brugada syndrome
      patients are not insignificant. Ventricular arrhythmia inducibility, spontaneous
      type I ECG, and presence of sinus node dysfunction might be considered as risk
      factors and used to drive long-term management.

PMID- 26215663
TI  - Atrioventricular Conduction Changes After CoreValve Transcatheter Aortic Valve
      Implantation.
AB  - INTRODUCTION AND OBJECTIVES: Conduction disturbances often occur after CoreValve
      transcatheter aortic valve implantation. The aim was to analyze which cardiac
      conduction changes occur in patients with aortic stenosis treated with this type
      of prosthesis. METHODS: A total of 181 patients with severe aortic stenosis
      treated with this prosthesis and studied by electrocardiography between April
      2008 and December 2013 were selected. A subgroup of 137 (75.7%) consecutive
      patients was studied by intracardiac electrocardiogram before and after
      prosthesis implantation. The primary endpoint of the study was the need for a
      permanent pacemaker within 72 hours after prosthesis implantation. Numerous
      variables to predict this possibility were analyzed. RESULTS: Following
      implantation, PR and QRS intervals were increased from 173+/-47 ms to 190+/-52ms
      (P < .01) and from 98+/-22ms to 129+/-24 ms (P < .01), whereas the A-H and H-V
      intervals were prolonged from 95+/-39ms to 108+/-41ms (P < .01) and from 54+/
      10ms to 66+/-23ms (P < .01). A total of 89 (49%) patients had new-onset left
      bundle-branch block, and 33 (25%) required a pacemaker within the first 72hours.
      The independent predictors for a pacemaker were baseline right bundle-branch
      block and prosthetic depth. Intracardiac intervals had no predictive value. In
      addition, 13 patients required a pacemaker after 72 hours. CONCLUSIONS: CoreValve
      prosthesis implantation has a high incidence of conduction disturbance, with left
      bundle-branch block being the most common. A total of 25% of patients required a
      permanent pacemaker. The need for a pacemaker was related to baseline right
      bundle-branch block and prosthetic depth.

PMID- 26215664
TI  - Healthcare practitioners' personal and professional values.
AB  - Personal and professional values of healthcare practitioners influence their
      clinical decisions. Understanding these values for individuals and across
      healthcare professions can help improve patient-centred decision-making by
      individual practitioners and interprofessional teams, respectively. We aimed to
      identify these values and integrate them into a single framework using Schwartz's
      values model. We searched Medline, Embase, PsycINFO, CINAHL and ERIC databases
      for articles on personal and professional values of healthcare practitioners and
      students. We extracted values from included papers and synthesized them into a
      single framework using Schwartz's values model. We summarised the framework
      within the context of healthcare practice. We identified 128 values from 50
      included articles from doctors, nurses and allied health professionals. A new
      framework for the identified values established the following broad healthcare
      practitioner values, corresponding to Schwartz values (in parentheses): authority
      (power); capability (achievement); pleasure (hedonism); intellectual stimulation
      (stimulation); critical-thinking (self-direction); equality (universalism);
      altruism (benevolence); morality (tradition); professionalism (conformity);
      safety (security) and spirituality (spirituality). The most prominent values
      identified were altruism, equality and capability. This review identified a
      comprehensive set of personal and professional values of healthcare
      practitioners. We integrated these into a single framework derived from
      Schwartz's values model. This framework can be used to assess personal and
      professional values of healthcare practitioners across professional groups, and
      can help improve practitioners' awareness of their values so they can negotiate
      more patient-centred decisions. A common values framework across professional
      groups can support shared education strategies on values and help improve
      interprofessional teamwork and decision-making.

PMID- 26215665
TI  - Evidence for a Pneumocystis carinii Flo8-like transcription factor: insights into
      organism adhesion.
AB  - Pneumocystis carinii (Pc) adhesion to alveolar epithelial cells is well
      established and is thought to be a prerequisite for the initiation of
      Pneumocystis pneumonia. Pc binding events occur in part through the major Pc
      surface glycoprotein Msg, as well as an integrin-like molecule termed PcInt1.
      Recent data from the Pc sequencing project also demonstrate DNA sequences
      homologous to other genes important in Candida spp. binding to mammalian host
      cells, as well as organism binding to polystyrene surfaces and in biofilm
      formation. One of these genes, flo8, a transcription factor needed for downstream
      cAMP/PKA-pathway-mediated activation of the major adhesion/flocculin Flo11 in
      yeast, was cloned from a Pc cDNA library utilizing a partial sequence available
      in the Pc genome database. A CHEF blot of Pc genomic DNA yielded a single band
      providing evidence this gene is present in the organism. BLASTP analysis of the
      predicted protein demonstrated 41 % homology to the Saccharomyces cerevisiae
      Flo8. Northern blotting demonstrated greatest expression at pH 6.0-8.0, pH
      comparable to reported fungal biofilm milieu. Western blot and
      immunoprecipitation assays of PcFlo8 protein in isolated cyst and tropic life
      forms confirmed the presence of the cognate protein in these Pc life forms.
      Heterologous expression of Pcflo8 cDNA in flo8Delta-deficient yeast strains
      demonstrated that the Pcflo8 was able to restore yeast binding to polystyrene and
      invasive growth of yeast flo8Delta cells. Furthermore, Pcflo8 promoted yeast
      binding to HEK293 human epithelial cells, strengthening its functional
      classification as a Flo8 transcription factor. Taken together, these data suggest
      that PcFlo8 is expressed by Pc and may exert activity in organism adhesion and
      biofilm formation.

PMID- 26215666
TI  - The ring vaccination trial: a novel cluster randomised controlled trial design to
      evaluate vaccine efficacy and effectiveness during outbreaks, with special
      reference to Ebola.
AB  - A World Health Organization expert meeting on Ebola vaccines proposed urgent
      safety and efficacy studies in response to the outbreak in West Africa. One
      approach to communicable disease control is ring vaccination of individuals at
      high risk of infection due to their social or geographical connection to a known
      case. This paper describes the protocol for a novel cluster randomised controlled
      trial design which uses ring vaccination.In the Ebola ca suffit ring vaccination
      trial, rings are randomised 1:1 to (a) immediate vaccination of eligible adults
      with single dose vaccination or (b) vaccination delayed by 21 days. Vaccine
      efficacy against disease is assessed in participants over equivalent periods from
      the day of randomisation. Secondary objectives include vaccine effectiveness at
      the level of the ring, and incidence of serious adverse events. Ring vaccination
      trials are adaptive, can be run until disease elimination, allow interim
      analysis, and can go dormant during inter-epidemic periods.

PMID- 26215667
TI  - Exploring the Potential of Predictive Analytics and Big Data in Emergency Care.
AB  - Clinical research often focuses on resource-intensive causal inference, whereas
      the potential of predictive analytics with constantly increasing big data sources
      remains largely unexplored. Basic prediction, divorced from causal inference, is
      much easier with big data. Emergency care may benefit from this simpler
      application of big data. Historically, predictive analytics have played an
      important role in emergency care as simple heuristics for risk stratification.
      These tools generally follow a standard approach: parsimonious criteria, easy
      computability, and independent validation with distinct populations. Simplicity
      in a prediction tool is valuable, but technological advances make it no longer a
      necessity. Emergency care could benefit from clinical predictions built using
      data science tools with abundant potential input variables available in
      electronic medical records. Patients' risks could be stratified more precisely
      with large pools of data and lower resource requirements for comparing each
      clinical encounter to those that came before it, benefiting clinical
      decisionmaking and health systems operations. The largest value of predictive
      analytics comes early in the clinical encounter, in which diagnostic and
      prognostic uncertainty are high and resource-committing decisions need to be
      made. We propose an agenda for widening the application of predictive analytics
      in emergency care. Throughout, we express cautious optimism because there are
      myriad challenges related to database infrastructure, practitioner uptake, and
      patient acceptance. The quality of routinely compiled clinical data will remain
      an important limitation. Complementing big data sources with prospective data may
      be necessary if predictive analytics are to achieve their full potential to
      improve care quality in the emergency department. 

PMID- 26215668
TI  - Negative Studies Are Usually Right: Vetting the Pseudoaxioms.

PMID- 26215669
TI  - Triage in the Time of Ebola: Research Across the Plexiglas Partition.

PMID- 26215670
TI  - The Effect of Pay for Performance in the Emergency Department on Patient Waiting
      Times and Quality of Care in Ontario, Canada: A Difference-in-Differences
      Analysis.
AB  - STUDY OBJECTIVE: In 2008, a pay-for-performance program was implemented in
      sequential waves in Ontario emergency departments (EDs), with the aim of reducing
      length of stay. We seek to evaluate its effects on ED length of stay and quality
      of care. METHODS: This was a retrospective observational study of ED visits in
      Ontario from April 1, 2007, to March 31, 2011, using multivariable difference-in
      differences analysis. Pay-for-performance hospitals and matched control sites
      were selected for each of 3 waves of the program. The primary outcome was 90th
      percentile ED length of stay; we also examined quality-of-care indicators.
      RESULTS: Pay-for-performance hospitals had a modest reduction in overall adjusted
      90th percentile ED length of stay in wave 1 (-36 minutes; 95% confidence interval
      [CI] -50 to -21 minutes), but not in wave 2 (-14 minutes; 95% CI -30 to 2
      minutes) or wave 3 (-7 minutes; 95% CI -23 to 8 minutes). ED admitted patients
      had a pronounced reduction in adjusted 90th percentile length of stay in wave 1 (
      225 minutes; 95% CI -263 to -188 minutes) and wave 2 (-133 minutes; 95% CI -175
      to -91 minutes). Nonadmitted low-acuity patients had reductions in adjusted 90th
      percentile ED length of stay in wave 1 (-24 minutes; 95% CI -29 to -18 minutes)
      and wave 3 (-19 minutes; 95% CI -24 to -14 minutes). The program did not
      negatively affect ED quality-of-care measures, such as 30-day mortality or
      readmission rates. CONCLUSION: Pay-for-performance was associated with modest
      overall benefits for ED length of stay without adversely affecting quality of
      care.

PMID- 26215671
TI  - Adverse drug reactions to self-medication: a study in a pharmacovigilance
      database.
AB  - Although self-medication is widely developed, there are few detailed data about
      its adverse drug reactions (ADRs). This study investigated the main
      characteristics of ADRs with self-medication recorded in the Midi-Pyrenees
      PharmacoVigilance between 2008 and 2014. Self-medication included first OTC drugs
      and second formerly prescribed drugs later used without medical advice (reuse of
      previously prescribed drugs). Among the 12 365 notifications recorded, 160 (1.3%)
      were related to SM with 186 drugs. Around three-forth of the ADRs were 'serious'.
      Mean age was 48.8 years with 56.3% females. The most frequent ADRs were
      gastrointestinal and neuropsychiatric and main drug classes involved NSAIDs,
      analgesics, and benzodiazepines. Phytotherapy-homeopathy accounted for 9.1% of
      drugs. 

PMID- 26215672
TI  - Trends over 30 years in the prevalence and severity of alveolar bone loss and the
      influence of smoking and socio-economic factors--based on epidemiological surveys
      in Sweden 1983-2013.
AB  - OBJECTIVE: Epidemiological studies of the prevalence of periodontitis over an
      extended time using the same methodology to investigate and classify
      periodontitis are sparse in the literature. Smoking and socio-economic factors
      have been proven to increase the risk for periodontal disease. The objective of
      this study was to investigate 30-year time trends, using the same methodology to
      classify the prevalence and severity in alveolar bone loss (ABL) and to
      investigate the influence of tobacco and socio-economic factors. METHODS: Four
      cross-sectional epidemiological studies in an adult population were performed in
      the county of Dalarna, Sweden, in 1983, 2003, 2008 and 2013. Random samples of
      787-1133 individuals aged 35-85 who answered a questionnaire about tobacco use
      and socio-economic factors were radiographically and clinically examined. A
      number of teeth, ABL and calculus visible on radiographs were registered. The
      severity of ABL as detected on radiographs was classified into no bone loss,
      moderate or severe. RESULTS: The prevalence of moderate ABL decreased from 45% in
      1983 to 16% in 2008, but increased to 33% in 2013 (P < 0.05). The prevalence of
      severe ABL remained the same from 1983 (7%) to 2013 (6%). Calculus visible on
      radiographs increased from 22% in 2008 to 32% in 2013 (P < 0.05). Socio-economic
      factors had limited impact on the severity of ABL. CONCLUSION: Moderate ABL and
      calculus visible on radiographs significantly increased between 2008 and 2013.
      Smoking was the strongest factor associated with ABL overall.

PMID- 26215673
TI  - Hyperpolarized NMR of plant and cancer cell extracts at natural abundance.
AB  - Natural abundance (13)C NMR spectra of biological extracts are recorded in a
      single scan provided that the samples are hyperpolarized by dissolution dynamic
      nuclear polarization combined with cross polarization. Heteronuclear 2D
      correlation spectra of hyperpolarized breast cancer cell extracts can also be
      obtained in a single scan. Hyperpolarized NMR of extracts opens many perspectives
      for metabolomics. 

PMID- 26215674
TI  - Relationship between dialysis adequacy and sleep quality in haemodialysis
      patients.
AB  - AIM AND OBJECTIVES: The aim of this study is to examine the relationship between
      dialysis adequacy and sleep quality in haemodialysis patients. BACKGROUND: Sleep
      problems are common in haemodialysis patients. Dialysis adequacy is one of the
      factors associated with sleep quality. Studies evaluating the association between
      dialysis adequacy and sleep quality in haemodialysis patients present different
      results. DESIGN: Descriptive and cross-sectional study. METHODS: This study was
      performed with a total of 119 patients who had applied to dialysis centres for
      haemodialysis treatment between January and March 2014. The data collection form
      consists of socio-demographic and medical characteristics as well as laboratory
      parameters. A modified Post-Sleep Inventory was used to examine sleep quality in
      the research. RESULTS: There were no statistically significant relationship
      between sleep quality and dialysis adequacy (p > 0.05). When the Post-Sleep
      Inventory scores were evaluated according to sleep quality, 63.0% of patients had
      poor sleep quality, and 37.0% had good sleep quality. Sleep quality was worse in
      unemployed patients (X(2) = 4.852; p = 0.025) and patients who smoked heavily (Z
      = 2.289; p = 0.022). CONCLUSIONS: In this study, there is no statistically
      significant relationship between dialysis adequacy and sleep quality. However, it
      was found that the majority of haemodialysis patients had poor sleep quality.
      RELEVANCE TO CLINICAL PRACTICE: Even if the dialysis adequacy of patients is at
      the recommended level, their sleep qualities may be poor. Therefore, evaluations
      of the sleep quality of haemodialysis patients during the clinical practice must
      be taken into consideration.

PMID- 26215675
TI  - Survival of patients with structurally-grouped TP53 mutations in ovarian and
      breast cancers.
AB  - The objective of this study was to determine if ovarian cancer patients with a
      TP53 mutation grouped by location of the mutation within the p53 protein
      structure exhibit differential survival outcomes. Data from patients with high
      grade serous ovarian cancer (HGS OvCa) (N = 316) or breast cancer (BrCa) (N =
      981) sequenced by The Cancer Genome Atlas (TCGA) was studied by Kaplan-Meier and
      Cox proportional hazards survival analysis. A TP53 DNA binding domain (BD)
      missense mutation (MM) occurred in 58.5% (185/316) of HGS OvCas and 16.8%
      (165/981) of BrCas. Patients with a TP53 DNA BD MM grouped by structural location
      had significantly different overall survival (OS) and progression free survival
      (PFS). Median OS (months) of HGS OvCa patients by structural group were: Sheet
      loop-helix stabilizers, 31.1; DNA minor groove residue R248, 33.6; Wild-type,
      34.2; all other MMs, 44.5; DNA major groove residues, 84.1, and zinc ion
      coordinating residues, 87.0 (log-rank p = 0.006). PFS of DNA major groove MM
      cases was longer than TP53 wild-type cases (19.1 versus 10.1 months, log-rank p =
      0.038). HGS OvCa and BrCa patients with structurally-grouped TP53 DNA BD MMs have
      different survival outcomes. 

PMID- 26215676
TI  - A contrasting function for miR-137 in embryonic mammogenesis and adult breast
      carcinogenesis.
AB  - MicroRNAs are differentially expressed in breast cancer cells and have been
      implicated in cancer formation, tumour invasion and metastasis. We investigated
      the miRNA expression profiles in the developing mammary gland. MiR-137 was
      expressed prominently in the developing mammary gland. When the miR-137 was over
      expressed in the embryo, the mammary epithelium became thickened. Moreover, genes
      associated with mammary gland formation such as Tbx3 and Lef1 were not expressed.
      This suggests that miR-137 induces gland formation and invasion. When miR-137 was
      over-expressed in MDA-MB-231 cells, their ability to form tumours in adult mice
      was significantly reduced. These data support miR-137 decides epithelial cell
      behavior in the human breast cancer. It also suggests that miR-137 is a potential
      therapeutic target for amelioration of breast cancer progression. 

PMID- 26215678
TI  - Should cost considerations be included in medical decisions? Not so sure....

PMID- 26215677
TI  - The pioneer factor PBX1 is a novel driver of metastatic progression in ERalpha
      positive breast cancer.
AB  - Over 30% of ERalpha breast cancer patients develop relapses and progress to
      metastatic disease despite treatment with endocrine therapies. The pioneer factor
      PBX1 translates epigenetic cues and mediates estrogen induced ERalpha binding.
      Here we demonstrate that PBX1 plays a central role in regulating the ERalpha
      transcriptional response to epidermal growth factor (EGF) signaling. PBX1
      regulates a subset of EGF-ERalpha genes highly expressed in aggressive breast
      tumours. Retrospective stratification of luminal patients using PBX1 protein
      levels in primary cancer further demonstrates that elevated PBX1 protein levels
      correlate with earlier metastatic progression. In agreement, PBX1 protein levels
      are significantly upregulated during metastatic progression in ERalpha-positive
      breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive
      tumours is partly mediated by genomic amplification of the PBX1 locus.
      Correspondingly, ERalpha-positive breast cancer patients carrying PBX1
      amplification are characterized by poor survival. Notably, we demonstrate that
      PBX1 amplification can be identified in tumor derived-circulating free DNA of
      ERalpha-positive metastatic patients. Metastatic patients with PBX1 amplification
      are also characterized by shorter relapse-free survival. Our data identifies PBX1
      amplification as a functional hallmark of aggressive ERalpha-positive breast
      cancers. Mechanistically, PBX1 amplification impinges on several critical
      pathways associated with aggressive ERalpha-positive breast cancer. 

PMID- 26215679
TI  - Should cost considerations be included in medical decisions? No.

PMID- 26215680
TI  - Hyperoxia: is it a biomarker for mortality?

PMID- 26215681
TI  - Should cost considerations be included in medical decisions? Yes.

PMID- 26215682
TI  - Understanding the benefits and harms of oxygen therapy: response to comments by
      Akca.

PMID- 26215683
TI  - Perioperative and bedside cerebral monitoring identifies cerebral injury after
      surgical correction of congenital aortic arch obstruction.

PMID- 26215684
TI  - Intensive care medicine curricula in Europe.

PMID- 26215685
TI  - Porokeratotic eccrine ostial and dermal duct nevus with a somatic homozygous or
      monoallelic variant of connexin 26.

PMID- 26215686
TI  - Toward a unifying framework for evolutionary processes.
AB  - The theory of population genetics and evolutionary computation have been evolving
      separately for nearly 30 years. Many results have been independently obtained in
      both fields and many others are unique to its respective field. We aim to bridge
      this gap by developing a unifying framework for evolutionary processes that
      allows both evolutionary algorithms and population genetics models to be cast in
      the same formal framework. The framework we present here decomposes the
      evolutionary process into its several components in order to facilitate the
      identification of similarities between different models. In particular, we
      propose a classification of evolutionary operators based on the defining
      properties of the different components. We cast several commonly used operators
      from both fields into this common framework. Using this, we map different
      evolutionary and genetic algorithms to different evolutionary regimes and
      identify candidates with the most potential for the translation of results
      between the fields. This provides a unified description of evolutionary processes
      and represents a stepping stone towards new tools and results to both fields. 

PMID- 26215687
TI  - Exon capture phylogenomics: efficacy across scales of divergence.
AB  - The evolutionary histories of species are not measured directly, but estimated
      using genealogies inferred for particular loci. Individual loci can have
      discordant histories, but in general we expect to infer evolutionary histories
      more accurately as more of the genome is sampled. High Throughput Sequencing
      (HTS) is now providing opportunities to incorporate thousands of loci in
      'phylogenomic' studies. Here, we used target enrichment to sequence c.3000
      protein-coding exons in a group of Australian skink lizards (crown group age c.80
      Ma). This method uses synthetic probes to 'capture' target exons that were
      identified in the transcriptomes of selected probe design (PD) samples. The
      target exons are then enriched in sample DNA libraries prior to performing HTS.
      Our main goal was to study the efficacy of enrichment of targeted loci at
      different levels of phylogenetic divergence from the PD species. In taxa sharing
      a common ancestor with PD samples up to c.20 Ma, we detected little reduction in
      efficacy, measured here as sequencing depth of coverage. However, at around 80
      Myr divergence from the PD species, we observed an approximately two-fold
      reduction in efficacy. A secondary goal was to develop a workflow for analysing
      exon capture studies of phylogenetically diverse samples, while minimizing
      potential bias. Our approach assembles each exon in each sample separately, by
      first recruiting short sequencing reads having homology to the corresponding
      protein sequence. In sum, custom exon capture provides a complement to existing,
      more generic target capture methods and is a practical and robust option across
      low-moderate levels of phylogenetic divergence. 

PMID- 26215688
TI  - Kidney cancer: Novel targets in altered tumour metabolism in kidney cancer.

PMID- 26215689
TI  - Paediatrics: Doxorubicin is not necessary in postoperative chemotherapy for Wilms
      tumour.

PMID- 26215693
TI  - Prostate cancer: Intrapatient heterogeneity in prostate cancer.

PMID- 26215695
TI  - Infectious disease: Blocking mTOR inhibits HIV-1.

PMID- 26215696
TI  - Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self
      interaction.
AB  - Laminins are key basement membrane molecules that influence several biological
      activities and are linked to a number of diseases. They are secreted as
      heterotrimeric proteins consisting of one alpha, one beta, and one gamma chain,
      followed by their assembly into a polymer-like sheet at the basement membrane.
      Using sedimentation velocity, dynamic light scattering, and surface plasmon
      resonance experiments, we studied self-association of three laminin (LM) N
      terminal fragments alpha-1 (hLM alpha-1N), alpha-5 (hLM alpha-5N) and beta-3 (hLM
      beta-3N) originating from the short arms of the human laminin alphabetagamma
      heterotrimer. Corresponding studies of the hLM alpha-1N C49S mutant, equivalent
      to the larval lethal C56S mutant in zebrafish, have shown that this mutation
      causes enhanced self-association behavior, an observation that provides a
      plausible explanation for the inability of laminin bearing this mutation to
      fulfill functional roles in vivo, and hence for the deleterious pathological
      consequences of the mutation on lens function. 

PMID- 26215697
TI  - Residual Conformational Entropies on the Sugar-Phosphate Backbone of Nucleic
      Acids: An Analysis of the Nucleosome Core DNA and the Ribosome.
AB  - A nucleic acid folds according to its free energy, but persistent residual
      conformational fluctuations remain along its sugar-phosphate backbone even after
      secondary and tertiary structures have been assembled, and these residual
      conformational entropies provide a rigorous lower bound for the folding free
      energy. We extend a recently reported algorithm to calculate the residual
      backbone entropy along a RNA or DNA given configuration of its bases and apply it
      to the crystallographic structures of the 23S ribosomal subunit and DNAs in the
      nucleosome core particle. In the 23S rRNAs, higher entropic strains are
      concentrated in helices and certain tertiary interaction platforms while residues
      with high surface accessibility and those not involved in base pairing generally
      have lower strains. Upon folding, residual backbone entropy in the 23S subunit
      accounts for an average free energy penalty of +0.47 (kcal/mol)/nt (nt =
      nucleotide) at 310 K. In nucleosomal DNAs, backbone entropies show periodic
      oscillations with sequence position correlating with the superhelical twist and
      shifts in the base-pair-step geometries, and nucleosome positioning on the bound
      DNA exerts strong influence over where entropic strains are located. In contrast
      to rRNAs, residual backbone entropies account for a free energy penalty of only
      +0.09 (kcal/mol)/nt in duplex relative to single-stranded DNAs. 

PMID- 26215698
TI  - Response surface methodology approach for optimization of simultaneous dye and
      metal ion ultrasound-assisted adsorption onto Mn doped Fe3O4-NPs loaded on AC:
      kinetic and isothermal studies.
AB  - In the present work, the usefulness of ultrasonic power as a dispersion and
      mixing tool to accelerate the adsorption of Safranin O (SO), methylene blue (MB),
      Pb(2+) ions and Cr(3+) ions onto the novel composite Fe3O4-NPs-AC adsorbent was
      investigated. This new material was extensively characterized and analyzed by
      different techniques such as XRD, FESEM, Raman spectroscopy and FT-IR. Central
      composite design (CCD) based on designed runs revealed that adsorbent mass,
      sonication time, MB concentration, SO concentration, Pb(2+) ion and Cr(3+) ion
      concentration and some of their interactions have significant contributions to
      the target compounds removal percentages. A combination of response surface
      methodology and Design-Expert software was used to qualify and estimate the
      influence and magnitude of each terms contribution to the response. An
      optimization study using the following investigated increments of the effective
      variables, adsorbent mass (0.01-0.03 g), sonication time (2-6 min), initial dye
      concentration (5-25 mg L(-1)), and initial metal ion concentration (20-60 mg L(
      1)), revealed that fixing the experimental variables at 0.025 g of Mn-Fe3O4-NPs
      AC, with a 3 min sonication time, and 20 mg L(-1) of MB, 10 mg L(-1) of SO, 38 mg
      L(-1) of Pb(2+) ions and 42 mg L(-1) of Cr(3+) ions at room temperature lead to
      the achievement of the best characteristics and performance. Conduction of 32
      experiments according to the limitations of CCD and a subsequent analysis of
      variance (ANOVA) gave useful information about the significant and also
      approximate contributions of each term (main and interaction of variables) in an
      empirical equation for the expected response. The results indicate that the R(2)
      values are more than 0.988 and the adjusted R(2) values are in reasonable
      agreement with R(2). Under the optimal conditions, the MB, SO, Pb(2+) ion and
      Cr(3+) ion removal efficiencies reached 99.54%, 98.87%, 80.25% and 99.54% after 3
      min, while their equilibrium data with high performance can be represented by
      Langmuir isotherms and a pseudo second-order kinetic model. The maximum
      adsorption capacities for the single component system, 229.4 mg g(-1) for MB,
      159.7 mg g(-1) for SO, 139.5 mg g(-1) for Pb(2+) ions and 267.4 mg g(-1) for
      Cr(3+) ions, support the high efficiency of Mn-Fe3O4-NPs-AC as a new adsorbent. 

PMID- 26215699
TI  - JTP-103237, a monoacylglycerol acyltransferase inhibitor, prevents fatty liver
      and suppresses both triglyceride synthesis and de novo lipogenesis.
AB  - AIM: Monoacyglycerol acyltransferases (MGATs) are known to play important roles
      in intestinal TG absorption. In contrast, the role of MGATs in the liver is still
      unclear. We investigated the effects of JTP-103237, a novel MGAT inhibitor, on
      hepatic MGAT activity and hepatic lipid metabolism. RESULTS: JTP-103237 reduced
      hepatic triglyceride content and hepatic MGAT activity in a high sucrose very low
      fat (HSVLF) diet induced fatty liver model. Interestingly, JTP-103237 suppressed
      not only triglyceride (TG) and diacylglycerol (DG) synthesis, but also fatty acid
      (FA) synthesis (de novo lipogenesis) in this model. JTP-103237 also suppressed
      lipogenesis-related gene expression, such as sterol regulatory element-binding
      protein 1-c. Moreover, JTP-103237 decreased plasma glucose levels and total
      cholesterol and reduced the accumulation of epididymal fats in HSVLF diet fed
      mice. CONCLUSION: In the present study, JTP-103237 prevented carbohydrate-induced
      fatty liver and suppressed both TG synthesis and de novo lipogenesis, suggesting
      MGAT inhibitor may prevent carbohydrate-induced metabolic disorders, including
      NAFLD, obesity and diabetes.

PMID- 26215700
TI  - Sodium-activated macrophages: the salt mine expands.
AB  - High sodium consumption has been raising interest as a putative environmental
      factor linking Western lifestyle to the growing epidemic of autoimmune and
      inflammatory diseases. Now Zhang and colleagues show that high sodium drives
      macrophage to acquire a new proinflammatory effector phenotype with a distinct
      signature, paving the path to assess the role of salt-activated macrophages in
      human disease. 

PMID- 26215702
TI  - Effect of Cements at Different Temperatures on the Clinical Performance and
      Marginal Adaptation of Inlay-Onlay Restorations In Vivo.
AB  - PURPOSE: To evaluate the clinical performance of inlays and onlays luted with two
      different resin cements, mixed at different temperatures and to evaluate the
      marginal adaptation of the restorations. MATERIALS AND METHODS: One hundred IPS
      e.max restorations (82 onlays, 18 inlays; 84 molars, 16 premolars) were placed in
      50 patients (28 females, 22 males, mean age, 33 years). The restorations were
      assigned to six groups according to the luting agent temperature (25 degrees C,
      37 degrees C, and 54 degrees C) and cement type (Variolink N high viscosity or G
      Cem Automix). All restorations were evaluated after 1 week and 1 year by two
      examiners using modified USPHS criteria. Replicas of 30 selected onlay
      restorations (5 per group) were assessed for marginal quality under a scanning
      electron microscope (SEM) at 200*. Marginal adaptation was quantitatively
      evaluated in terms of percentage of gap formation, and marginal gap width was
      measured. RESULTS: After 1 year, the total survival rates of the Variolink N high
      viscosity group and G-Cem Automix group were 100% and 93.8%, respectively. Three
      debondings occurred with the G-Cem Automix group, one from each temperature
      group. For 1-year clinical service time, no significant difference was noticed in
      the marginal adaptation of Variolink N high viscosity groups and the 37 degrees C
      G-Cem Automix group, while 25 degrees C and 54 degrees C G-Cem Automix groups'
      marginal adaptation scores decreased (p < 0.05). Regarding the SEM evaluations,
      Variolink N high viscosity cement groups showed better marginal adaptation than G
      Cem Automix cement groups (p < 0.05). Cementation with the cements preheated to
      37 degrees C increased continuous margins in both enamel-cement and cement
      ceramic interfaces, but these results were not statistically significant (p >
      0.05). Cements at different temperatures did not have significant effects on
      marginal gap widths of the restorations. CONCLUSIONS: The restorations cemented
      with Variolink N high viscosity cement mixed at the three tested temperatures
      exhibited better treatment options than the self-adhesive groups. Preheating the
      self-adhesive cement (G-Cem Automix) to 37 degrees C can be an effective method
      to have better marginal adaptation than the other self-adhesive groups (25
      degrees C, 54 degrees C) tested in this study.

PMID- 26215703
TI  - Cytotoxicity and migration of fibroblasts on two types of calcium sulfate
      dihydrate.
AB  - AIM: The aim of the present study was to compare cytotoxicity and migration
      ability of L929 on medical-grade calcium sulfate dihydrate (MCS) with commercial
      calcium sulfate dihydrate (CCS). METHODS: Samples of both freshly-mixed and set
      states of MCS and CCS were extracted in culture medium and tested for
      cytotoxicity according to International Organization of Standardization 10993
      5:2009. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
      was used, and the percentage of cell viability was calculated. Thirty petri
      dishes were divided into three equal groups: polystyrene (control), CCS, and MCS.
      In each petri dish, triplicate wells were made on the agarose overlay on the
      material. The central well was occupied with L929 cell suspension, one well was
      filled with platelet-derived growth factor-BB, and the remaining well with Hanks'
      Balanced Salt Solution. After incubation, the migration distances were measured
      and the corrected migration distances were calculated. The final step involved
      scanning electron microscopy (SEM). RESULTS: The CCS had significantly less cell
      viability than MCS at a high extracted concentration (P < 0.001) in both samples.
      The mean corrected migration of MCS was significantly greater than that of CCS (P
      < 0.05). SEM showed that L929 cells on MCS exhibited an elongated spindle shape.
      CONCLUSION: MCS was less cytotoxic and provided greater migration of L929
      fibroblasts compared with CCS.

PMID- 26215701
TI  - RHOBTB3 promotes proteasomal degradation of HIFalpha through facilitating
      hydroxylation and suppresses the Warburg effect.
AB  - Hypoxia-inducible factors (HIFs) are master regulators of adaptive responses to
      low oxygen, and their alpha-subunits are rapidly degraded through the
      ubiquitination-dependent proteasomal pathway after hydroxylation. Aberrant
      accumulation or activation of HIFs is closely linked to many types of cancer.
      However, how hydroxylation of HIFalpha and its delivery to the ubiquitination
      machinery are regulated remains unclear. Here we show that Rho-related BTB domain
      containing protein 3 (RHOBTB3) directly interacts with the hydroxylase PHD2 to
      promote HIFalpha hydroxylation. RHOBTB3 also directly interacts with the von
      Hippel-Lindau (VHL) protein, a component of the E3 ubiquitin ligase complex,
      facilitating ubiquitination of HIFalpha. Remarkably, RHOBTB3 dimerizes with
      LIMD1, and constructs a RHOBTB3/LIMD1-PHD2-VHL-HIFalpha complex to effect the
      maximal degradation of HIFalpha. Hypoxia reduces the RHOBTB3-centered complex
      formation, resulting in an accumulation of HIFalpha. Importantly, the expression
      level of RHOBTB3 is greatly reduced in human renal carcinomas, and RHOBTB3
      deficiency significantly elevates the Warburg effect and accelerates xenograft
      growth. Our work thus reveals that RHOBTB3 serves as a scaffold to organize a
      multi-subunit complex that promotes the hydroxylation, ubiquitination and
      degradation of HIFalpha. 

PMID- 26215704
TI  - Infrared nanospectroscopy characterization of oligomeric and fibrillar aggregates
      during amyloid formation.
AB  - Amyloids are insoluble protein fibrillar aggregates. The importance of
      characterizing their aggregation has steadily increased because of their link to
      human diseases and material science applications. In particular, misfolding and
      aggregation of the Josephin domain of ataxin-3 is implicated in spinocerebellar
      ataxia-3. Infrared nanospectroscopy, simultaneously exploiting atomic force
      microscopy and infrared spectroscopy, can characterize at the nanoscale the
      conformational rearrangements of proteins during their aggregation. Here we
      demonstrate that we can individually characterize the oligomeric and fibrillar
      species formed along the amyloid aggregation. We describe their secondary
      structure, monitoring at the nanoscale an alpha-to-beta transition, and couple
      these studies with an independent measurement of the evolution of their intrinsic
      stiffness. These results suggest that the aggregation of Josephin proceeds from
      the monomer state to the formation of spheroidal intermediates with a native
      structure. Only successively, these intermediates evolve into misfolded
      aggregates and into the final fibrils. 

PMID- 26215705
TI  - Early and dynamic changes in gene expression in septic shock patients: a genome
      wide approach.
AB  - BACKGROUND: As early and appropriate care of severe septic patients is associated
      with better outcome, understanding of the very first events in the disease
      process is needed. Pan-genomic analyses offer an interesting opportunity to study
      global genomic response within the very first hours after sepsis. The objective
      of this study was to investigate the systemic genomic response in severe
      intensive care unit (ICU) patients and determine whether patterns of gene
      expression could be associated with clinical severity evaluated by the severity
      score. METHODS: Twenty-eight ICU patients were enrolled at the onset of septic
      shock. Blood samples were collected within 30 min and 24 and 48 h after shock and
      genomic response was evaluated using microarrays. The genome-wide expression
      pattern of blood leukocytes was sequentially compared to healthy volunteers and
      after stratification based on Simplified Acute Physiology Score II (SAPSII) score
      to identify potential mechanisms of dysregulation. RESULTS: Septic shock induces
      a global reprogramming of the whole leukocyte transcriptome affecting multiple
      functions and pathways (>71% of the whole genome was modified). Most altered
      pathways were not significantly different between SAPSII-high and SAPSII-low
      groups of patients. However, the magnitude and the duration of these alterations
      were different between these two groups. Importantly, we observed that the more
      severe patients did not exhibit the strongest modulation. This indicates that
      some regulation mechanisms leading to recovery seem to take place at the early
      stage. CONCLUSIONS: In conclusion, both pro- and anti-inflammatory processes,
      measured at the transcriptomic level, are induced within the very first hours
      after septic shock. Interestingly, the more severe patients did not exhibit the
      strongest modulation. This highlights that not only the responses mechanisms by
      themselves but mainly their early and appropriate regulation are crucial for
      patient recovery. This reinforces the idea that an immediate and tailored
      aggressive care of patients, aimed at restoring an appropriately regulated immune
      response, may have a beneficial impact on the outcome.

PMID- 26215706
TI  - Neutrophil extracellular traps in the host defense against sepsis induced by
      Burkholderia pseudomallei (melioidosis).
AB  - BACKGROUND: Neutrophil extracellular traps (NETs) are a central player in the
      host response to bacteria: neutrophils release extracellular DNA (nucleosomes)
      and neutrophil elastase to entrap and kill bacteria. We studied the role of NETs
      in Burkholderia pseudomallei infection (melioidosis), an important cause of Gram
      negative sepsis in Southeast Asia. METHODS: In a prospective observational study,
      circulating nucleosomes and neutrophil elastase were assayed in 44 patients with
      Gram-negative sepsis caused by B. pseudomallei (melioidosis) and 82 controls.
      Functional assays included human neutrophil stimulation and killing assays and a
      murine model of B. pseudomallei infection in which NET function was compromised
      using DNase. Specified pathogen-free 8- to 12-week-old C57BL/6 mice were
      sacrificed post-infection to assess bacterial loads, inflammation, and pathology.
      RESULTS: Nucleosome and neutrophil elastase levels were markedly elevated in
      patients compared to controls. NETs killed B. pseudomallei effectively, and
      neutrophils stimulated with B. pseudomallei showed increased elastase and DNA
      release in a time- and dose-dependent matter. In mice, NET disruption with
      intravenous DNase administration resulted in decreased nucleosome levels.
      Although DNase treatment of mice resulted in diminished liver inflammation, no
      differences were observed in bacterial dissemination or systemic inflammation.
      CONCLUSION: B. pseudomallei is a potent inducer of NETosis which was reflected by
      greatly increased levels of NET-related components in melioidosis patients.
      Although NETs exhibited antibacterial activity against B. pseudomallei, NET
      formation did not protect against bacterial dissemination and inflammation during
      B. pseudomallei-induced sepsis.

PMID- 26215707
TI  - The receptor for advanced glycation end products in ventilator-induced lung
      injury.
AB  - BACKGROUND: Mechanical ventilation (MV) can cause ventilator-induced lung injury
      (VILI). The innate immune response mediates this iatrogenic inflammatory
      condition. The receptor for advanced glycation end products (RAGE) is a
      multiligand receptor that can amplify immune and inflammatory responses. We
      hypothesized that RAGE signaling contributes to the pro-inflammatory state
      induced by MV. METHODS: RAGE expression was analyzed in lung brush and lavage
      cells obtained from ventilated patients and lung tissue of ventilated mice.
      Healthy wild-type (WT) and RAGE knockout (KO) mice were ventilated with
      relatively low (approximately 7.5 ml/kg) or high (approximately 15 ml/kg) tidal
      volume. Positive end-expiratory pressure was set at 2 cm H2O during both MV
      strategies. Also, WT and RAGE KO mice with lipopolysaccharide (LPS)-induced lung
      injury were ventilated with the above described ventilation strategies. In
      separate experiments, the contribution of soluble RAGE, a RAGE isoform that may
      function as a decoy receptor, in ventilated RAGE KO mice was investigated. Lung
      wet-to-dry ratio, cell and neutrophil influx, cytokine and chemokine
      concentrations, total protein levels, soluble RAGE, and high-mobility group box 1
      (HMGB1) presence in lung lavage fluid were analyzed. RESULTS: MV was associated
      with increased RAGE mRNA levels in both human lung brush samples and lung tissue
      of healthy mice. In healthy high tidal volume-ventilated mice, RAGE deficiency
      limited inflammatory cell influx. Other VILI parameters were not affected. In our
      second set of experiments where we compared RAGE KO and WT mice in a 2-hit model,
      we observed higher pulmonary cytokine and chemokine levels in RAGE KO mice
      undergoing LPS/high tidal volume MV as compared to WT mice. Third, in WT mice
      undergoing the LPS/high tidal volume MV, we observed HMGB1 presence in lung
      lavage fluid. Moreover, MV increased levels of soluble RAGE in lung lavage fluid,
      with the highest levels found in LPS/high tidal volume-ventilated mice.
      Administration of soluble RAGE to LPS/high tidal volume-ventilated RAGE KO mice
      attenuated the production of inflammatory mediators. CONCLUSIONS: RAGE was not a
      crucial contributor to the pro-inflammatory state induced by MV. However, the
      presence of sRAGE limited the production of pro-inflammatory mediators in our 2
      hit model of LPS and high tidal volume MV.

PMID- 26215709
TI  - The Role of the NDQ Motif in Sodium-Pumping Rhodopsins.
AB  - Sodium-pumping rhodopsins (NaRs) are light-driven outward Na(+) pumps. NaRs have
      a conserved Asn, Asp, and Gln motif (NDQ) in the third transmembrane helix (helix
      C). The NDQ motif is thus expected to play a crucial role in the operation of the
      Na(+) pump. Herein, we studied the photocycles of the NDQ-motif mutants of
      Krokinobacter rhodopsin 2 (KR2), the first discovered NaR, by flash photolysis,
      to obtain insight into the mechanism of Na(+) transport. For example, the KR2
      N112A mutant did not accumulate the transient red-shifted Na(+)-bound state,
      suggesting that Asn112 is vital for the binding of Na(+) ions. Additionally,
      Q123A and Q123V mutants showed significantly slower Na(+) uptake and recovery of
      the initial state. Overall, the Gln123 residue was found to contribute to the
      optimization of the kinetics of sodium-ion uptake and release. These results
      demonstrate that the cooperative operation of the three residues of the NDQ motif
      are important in the operation of the Na(+) pump.

PMID- 26215710
TI  - Pharmacological evidence for a role of the transient receptor potential canonical
      3 (TRPC3) channel in endoplasmic reticulum stress-induced apoptosis of human
      coronary artery endothelial cells.
AB  - Unresolved endoplasmic reticulum (ER) stress, with the subsequent persistent
      activation of the unfolded protein response (UPR) is a well-recognized mechanism
      of endothelial cell apoptosis with a major impact on the integrity of the
      endothelium during the course of cardiovascular diseases. As in other cell types,
      Ca(2+) influx into endothelial cells can promote ER stress and/or contribute to
      mechanisms associated with it. In previous work we showed that in human coronary
      artery endothelial cells (HCAECs) the Ca(2+)-permeable non-selective cation
      channel Transient Receptor Potential Canonical 3 (TRPC3) mediates constitutive
      Ca(2+) influx which is critical for operation of inflammatory signaling in these
      cells, through a mechanism that entails coupling of TRPC3 constitutive function
      to activation of Ca(2+)/calmodulin-dependent protein kinase II (CAMKII). TRPC3
      has been linked to UPR signaling and apoptosis in cells other than endothelial,
      and CAMKII is a mediator of ER stress-induced apoptosis in various cell types,
      including endothelial cells. In the present work we used a pharmacological
      approach to examine whether in HCAECs TRPC3 and CAMKII also contribute to
      mechanisms of ER stress-induced apoptosis. The findings show for the first time
      that in HCAECs activation of the UPR and the subsequent ER stress-induced
      apoptosis exhibit a strong requirement for constitutive Ca(2+) influx and that
      TRPC3 contributes to this process. In addition, we obtained evidence indicating
      that, similar to its roles in non-endothelial cells, CAMKII participates in ER
      stress-induced apoptosis in HCAECs. 

PMID- 26215711
TI  - Targeting specific bacteria in the oral microbiome.
AB  - A lack of tools that kill selected members of the oral microbiome has hampered
      the ability to study specific roles of bacteria within bacterial communities.
      Work by Guo et al. shows the potential of antimicrobial peptides as a tool to
      assess the role of individual species in the microbial community. 

PMID- 26215712
TI  - Oral cavity and oropharyngeal squamous cell carcinoma--an update.
AB  - Oral cavity squamous cell carcinoma (OC-SCC) is the most common malignancy of the
      head and neck (excluding nonmelanoma skin cancer). Recent trends have shown a
      dramatic rise in the incidence of oropharyngeal squamous cell carcinoma (OP-SCC),
      with a marked increase in lesions related to human papillomavirus infection. This
      update presents the latest evidence regarding OC-SCC and OP-SCC. In particular,
      the authors compare and contrast tumors at these two sites with respect to
      epidemiology, etiopathogenesis, clinicopathologic presentation, clinical
      assessment, imaging, management, and prognosis. It is important for clinicians to
      be aware of differences between OC-SCC and OP-SCC so that appropriate patient
      education and multidisciplinary care can be provided to optimize outcomes.

PMID- 26215708
TI  - Determinants of survival and major amputation after peripheral endovascular
      intervention for critical limb ischemia.
AB  - OBJECTIVE: Our objective was to analyze periprocedural and 1-year outcomes of
      peripheral endovascular intervention (PVI) for critical limb ischemia (CLI).
      METHODS: We reviewed 1244 patients undergoing 1414 PVIs for CLI (rest pain, 29%;
      tissue loss, 71%) within the Vascular Study Group of New England (VSGNE) from
      January 2010 to December 2011. Overall survival (OS), amputation-free survival
      (AFS), and freedom from major amputation at 1 year were analyzed using the Kaplan
      Meier method. Cox proportional hazards models were used to calculate hazard
      ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The number of arteries
      treated during each procedure were 1 (49%), 2 (35%), 3 (12%), and >=4 (5%).
      Target arterial segments and TransAtlantic Inter-Society Consensus
      classifications were aortoiliac, 27% (A, 48%; B, 28%; C, 12%; and D, 12%);
      femoral-popliteal, 48% (A, 29%; B, 34%; C, 20%; and D, 17%); and infrapopliteal,
      25% (A, 17%; B, 14%; C, 25%; D, 44%). Technical success was 92%. Complications
      included access site hematoma (5.0%), occlusion (0.3%), and distal embolization
      (2.4%). Mortality and major amputation rates were 2.8% and 2.2% at 30 days,
      respectively. Overall percutaneous or open reintervention rate was 8.0% during
      the first year. At 1-year, OS, AFS, and freedom from major amputation were 87%,
      87%, and 94% for patients with rest pain and 80%, 71%, and 81% for patients with
      tissue loss. Independent predictors of reduced 1-year OS (C index = .74) included
      dialysis (HR, 3.8; 95% CI, 2.8-5.1; P < .01), emergency procedure (HR, 2.5; 95%
      CI, 1.0-6.2; P = .05), age >80 years (HR, 2.2; 95% CI, 1.7-2.8; P < .01), not
      living at home preoperatively (HR, 2.0; 95% CI, 1.4-2.8; P < .01), creatinine
      >1.8 mg/dL (HR, 1.9; 95% CI, 1.3-2.8; P < .01), congestive heart failure (HR,
      1.7; 95% CI, 1.3-2.2; P < .01), and chronic beta-blocker use (HR, 1.4; 95% CI,
      1.0-1.9; P = .03), whereas independent preoperative ambulation (HR, 0.7; 95% CI,
      0.6-0.9; P = .014) was protective. Independent predictors of major amputation (C
      index = .69) at 1 year included dialysis (HR, 2.7; 95% CI, 1.6-4.5; P < .01),
      tissue loss (HR, 2.0; 95% CI, 1.1-3.7; P = .02), prior major contralateral
      amputation (HR, 2.0; 95% CI, 1.1-3.5; P = .02), non-Caucasian race (HR, 1.7; 95%
      CI, 1.0-2.9; P = .045), and male gender (HR, 1.6; 95% CI, 1.1-2.6; P = .03),
      whereas smoking (HR, .60; 95% CI, 0.4-1.0; P = .042) was protective. CONCLUSIONS:
      Survival and major amputation after PVI for CLI are associated with different
      patient characteristics. Dialysis dependence is a common predictor that portends
      especially poor outcomes. These data may facilitate efforts to improve patient
      selection and, after further validation, enable risk-adjusted outcome reporting
      for CLI patients undergoing PVI.

PMID- 26215713
TI  - Magnetic resonance imaging (MRI) of the lumbar spine with dedicated G-scan
      machine in the upright position: a retrospective study and our experience in 10
      years with 4305 patients.
AB  - PURPOSE: To evaluate the pathological changes of the lumbar spine and the
      instability of the lumbar intervertebral joints observed in patients with low
      back pain, with the study of the transition from supine to orthostatic position
      through the use of dedicated MRI-G-scan machine. MATERIALS AND METHODS: Within 10
      years, 4305 patients, aged between 21 and 80 years old, with history of low back
      pain with or without sciatica, underwent MRI examinations in upright and in
      supine position. The open MRI-scanner used is Esaote G-scan, which enables the
      acquisition of images in supine and standing positions. The used sequences were
      sagittal T2-weighted FSE, T1-weighted SE and axial 3D HYCE. Patients were divided
      into two groups: "negatives", with no changes in the two positions (supine and
      upright), and "positives", with MRI modifications of imaging in upright position.
      RESULTS: Orthostatic examination showed MRI changes in 2870 out of 4305 (66.6%)
      patients, including 1252 males and 1618 females. CONCLUSIONS: The G-scan is
      useful to assess instability of the lumbar spine detecting hidden modifications
      of protrusions and/or herniated discs already present in the supine position. It
      is also helpful in assessing the presence or modification of spondylolisthesis
      and lumbar canal stenosis.

PMID- 26215714
TI  - Primary paraganglioma of the lung: a case report.
AB  - INTRODUCTION: Primary paraganglioma of the lung is a rare tumor of which few
      cases are reported in literature. Both solitary and diffuse primary pulmonary
      paragangliomas are described. The solitary form of this tumor is rare. CASE
      PRESENTATION: We report the case of a 63-year-old Caucasian man with cough,
      intermittent palpitations and dyspnea. A contrast-enhanced computed tomography
      scan of his chest revealed a rounded, high-density lesion with irregular profiles
      measuring 24mm in diameter in the middle lobe. The lesion was suggestive of
      malignancy. Fine-needle aspiration cytology was performed. The results of the
      cytological tests were positive for malignant cells. Surgical resection was the
      choice of treatment. The results of the biochemical tests and postoperative
      histological examination allowed a definitive diagnosis: primary pulmonary
      paraganglioma. CONCLUSIONS: Paragangliomas are identified and characterized with
      the use of computed tomography and other imaging methods, but for a definitive
      diagnosis, histopathological evaluation is necessary. We report a rare case of a
      primary pulmonary paraganglioma that was treated surgically. This case report
      adds valuable knowledge to the literature on pulmonary paragangliomas.

PMID- 26215715
TI  - Pregnancy outcomes following first-trimester exposure to topical retinoids: a
      systematic review and meta-analysis.
AB  - Evaluation of human data regarding the outcomes of topical-retinoid-exposed
      pregnancies is important in terms of counselling pregnant women with inadvertent
      exposure. The objective of this study was thus to determine whether exposure to
      topical retinoids leads to an increase in the risk of adverse pregnancy outcomes.
      We carried out a search using the Medline, Embase, Web of Science and Cochrane
      Central Register of Controlled Trials databases from inception to 4 December
      2014. The selection, review and quality assessment of the studies were carried
      out by two independent reviewers according to predetermined inclusion criteria.
      Odds ratios (ORs) were calculated by the random effects method. This meta
      analysis, including a total of 654 pregnant women who were exposed to topical
      retinoids, and 1375 unexposed control pregnant women, did not detect significant
      increases in rates of major congenital malformations [OR 1.22, 95% confidence
      interval (CI) 0.65-2.29], spontaneous abortions (OR 1.02, 95% CI 0.64-1.63),
      stillbirth (OR 2.06, 95% CI 0.43-9.86), elective termination of pregnancy (OR
      1.89, 95% CI 0.52-6.80), low birthweight (OR 1.01, 95% CI, 0.31-3.27) or
      prematurity (OR 0.69, 95% CI 0.39-1.23). No significant heterogeneity was
      detected among the studies for the evaluated outcomes. The present meta-analysis
      ruled out a major increase in the rates of major congenital malformations,
      spontaneous abortions, low birthweight and prematurity. This result may be used
      primarily in reassuring women who were inadvertently exposed to topical retinoids
      during their pregnancy. However, the statistical power is not adequate to justify
      the use of topical retinoids during pregnancy. 

PMID- 26215717
TI  - The Ethics of Access: Who Is Offered a Cesarean Delivery, and Why?

PMID- 26215716
TI  - The significance of NTR1 expression and its correlation with beta-catenin and
      EGFR in gastric cancer.
AB  - BACKGROUND: Several reports indicate the high-affinity receptor of NT
      (neurotensin), NTR1 (neurotensin receptor 1), in numerous detrimental functions
      linked to neoplastic progression of several cancer types. Recently, it has also
      been shown that NTR1 gene is a target of the Wnt/APC oncogenic pathways connected
      with the beta-catenin/Tcf transcriptional complex and NT can stimulate cancer
      proliferation in an EGFR-dependent mechanism. In this study, we explored NTR1,
      beta-catenin and EGFR expression in gastric cancer. The possible associations of
      NTR1 expression with clinicopathological factors, prognosis, beta-catenin and
      EGFR were analyzed. METHODS: NTR1, beta-catenin and EGFR expression in gastric
      cancer tissues and the adjacent normal tissues of 210 cases was detected by
      Immunohistochemistry. The possible associations of NTR1 expression with
      clinicopathological data, prognosis, beta-catenin and EGFR were analyzed.
      RESULTS: 1. NTR1 expression in tumor tissues was significantly higher than that
      in adjacent normal tissues (P <0 .01). 2. Its expression was positively
      correlated with pathological grade, T stage, N stage and TNM stage and was not
      correlated with sex, age, tumor size and Lauren's classification. 3. A co
      expression of NTR1 and nuclear beta-catenin was in 53 (25.2 %) of cases and NTR1
      expression was positively correlated with beta-catenin nuclear translocation.
      NTR1 expression was not correlated with EGFR expression, but at a critical value
      (P = 0.05). 4. By log-rank test, higher expression of NTR1, higher pathological
      grade, diffusion Lauren's classification and advanced TNM stage showed worse
      prognosis (P <0 .05). Age, sex, tumor size, beta-catenin and EGFR had no
      prognostic significance. Multivariate Cox analysis showed that NTR1 expression
      and TNM clinical stage (P <0 .05) were the independent prognostic factors for
      patients with GC. CONCLUSION: By immunohistochemistry, we found that a high
      expression of NTR1 in GC specimens, which showed a bad prognosis, besides, NTR1
      expression was related to invasion and migration of GC. These findings provide
      new and important information on the progression of GC. This study indicated that
      NTR1 may play an important role in tumor progression of GC and have its potential
      to be a predictive biomarker or a therapeutic molecular target in GC. The
      interaction between NTR1 and beta-catenin may participate in the development of
      GC. However, the relationship between NTR1 and EGFR needs to be further
      investigated.

PMID- 26215718
TI  - Digital Dating: Online Profile Content of Older and Younger Adults.
AB  - OBJECTIVES: Older adults are utilizing online dating websites in increasing
      numbers. Adults of different ages may share motivations for companionship and
      affection, but dating profiles may reveal differences in adults' goals. Theories
      addressing age-related changes in motivation suggest that younger adults are
      likely to emphasize themselves, achievements, attractiveness, and sexuality.
      Older adults are likely to present themselves positively and emphasize their
      existing relationships and health. METHOD: We collected 4,000 dating profiles
      from two popular websites to examine age differences in self-presentations. We
      used stratified sampling to obtain a sample equally divided by gender, aged 18-95
      years. We identified 12 themes in the profiles using Linguistic Inquiry and Word
      Count software (Pennebaker, Booth, & Francis, 2007). RESULTS: Regression analyses
      revealed that older adults were more likely to use first-person plural pronouns
      (e.g., we, our) and words associated with health and positive emotions. Younger
      adults were more likely to use first-person singular pronouns (e.g., I, my) and
      words associated with work and achievement. DISCUSSION: Findings suggest that
      younger adults enhance the "self" when seeking romantic partnership. In contrast,
      older adults are more positive in their profiles and focus more on connectedness
      and relationships to others.

PMID- 26215719
TI  - Corrigendum.
AB  - Scadding GW, Eifan AO, Lao-Araya M, Penagos M, Poon SY, Steveling E, Yan R,
      Switzer A, Phippard D, Togias A, Shamji MH, Durham SR. Effect of grass pollen
      immunotherapy on clinical and local immune response to nasal allergen challenge.
      Allergy 2015;70;689-696. In the article 'Effect of grass pollen immunotherapy on
      clinical and local immune response to nasal allergen challenge', one of the
      authors was accidentally omitted from the author list. In the published print
      version, the author list is given as below: G. W. Scadding, A. Eifan, M. Lao
      Araya, M. Penagos, S. Y. Poon, E. Steveling, R. Yan, A. Switzer, A.O. Eifan, A.
      Togias, M. H. Shamji & S. R. Durham The correct author list is as follows: G. W.
      Scadding, A.O. Eifan, M. Lao-Araya, M. Penagos, S. Y. Poon, E. Steveling, R. Yan,
      A. Switzer, D. Phippard, A. Togias, M. H. Shamji & S. R. DurhamWe apologize for
      any inconvenience caused.

PMID- 26215720
TI  - Serum biomarkers for the early diagnosis of TIA: The MIND-TIA study protocol.
AB  - BACKGROUND: A Transient Ischaemic Attack (TIA) bears a high risk of a subsequent
      ischaemic stroke. Adequate diagnosis of a TIA should be followed immediately by
      the start of appropriate preventive therapy, including antiplatelets. The
      diagnosis of a TIA based on symptoms and signs only is notoriously difficult and
      biomarkers of brain ischaemia might improve the recognition, and target
      management and prognosis of TIA patients. Our aim is to quantify the added
      diagnostic value of serum biomarkers of brain ischaemia in patients suspected of
      TIA. METHODS/DESIGN:  STUDY DESIGN: a cross-sectional diagnostic accuracy study
      with an additional six month follow-up period. STUDY POPULATION: 350 patients
      suspected of TIA in the primary care setting. Patients suspected of a TIA will be
      recruited by at least 200 general practitioners (GPs) in the catchment area of
      seven TIA outpatient clinics willing to participate in the study. In all patients
      a blood sample will be drawn as soon as possible after the patient has contacted
      the GP, but at least within 72 h after onset of symptoms. Participants will be
      referred by the GP to the regional TIA outpatient clinic for additional
      investigations, including brain imaging. The 'definite' diagnosis (reference
      standard) will be made by a panel consisting of three experienced neurologists
      who will use all available diagnostic information and the clinical information
      obtained during the outpatient clinic assessment, and a six month follow-up
      period. The diagnostic accuracy, and value in addition to signs and symptoms of
      candidate serum biomarkers will be assessed in terms of discrimination with C
      statistics, and calibration with plots. We aim to include 350 suspected cases,
      with 250 patients with indeed definite TIA (or minor stroke) according to the
      panel. DISCUSSION: We hope to find novel biomarkers that will enable a rapid and
      accurate diagnosis of TIA. This would largely improve the management and
      prognosis of such patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier
      NCT01954329.

PMID- 26215721
TI  - Assessment of knowledge regarding tuberculosis among non-medical university
      students in Bangladesh: a cross-sectional study.
AB  - BACKGROUND: Tuberculosis (TB) is the second leading cause of human death and TB
      is one of the major public health problems in Bangladesh. The aim of the present
      study was to assess the Knowledge about TB among non-medical university students
      in Bangladesh. METHODS: A cross-sectional survey was performed on 839 non-medical
      university students. Data were collected from University of Rajshahi from March
      to August 2013 using a standard semi-structured questionnaire. Chi-square test
      was utilized to find the factors which are associated with students' knowledge
      about TB. RESULTS: Among 839 students, male and female were 68.2 % and 31.8 %
      respectively. Most of the students (94.4 %) were informed about the term TB,
      among them 50 % got information from electronic media. More than 50 % students
      believed that TB is a communicable disease, 42.8 % students agreed that bacteria
      is an agent for TB, most of the subjects (93 %) had the knowledge about the
      vaccination against TB and 97.6 % students believed that TB is curable. However,
      students had poor knowledge about latent TB (13.7 %) and DOTs program (28.5 %).
      chi (2)-test demonstrated that gender, residence, type of family and parents
      education were associated with students' knowledge of TB. CONCLUSION: In the
      present study demonstrated that the level of general knowledge about TB was
      insufficient among non-medical university students. Consequently, health
      education program is needed to improve the knowledge among university students
      regarding TB.

PMID- 26215722
TI  - A Review Over the Past 15 Years of the Management of the Internal Piriform Apex
      Sinus Tract of a Branchial Pouch Anomaly and Case Description.
AB  - OBJECTIVES: Literature review of treating the piriform apex sinus tract through
      microlaryngoscopy and a case description. REVIEW METHODS: Fourteen papers were
      identified in PubMed using the search criteria of piriform sinus fistula,
      microlaryngoscopic repair, and endoscopy. Institutional Review Board approval was
      obtained. RESULTS: One hundred forty-five cases including ours were available for
      review, with 182 procedures. Sixty-two cases were male, 73 female, and 10 genders
      were not reported. Multiple treatment options were used, including
      electrocautery, chemocautery, mass excision, fibrin glue, lasers, suture closure,
      or combination of stated modalities. Of the 182 procedures, 147 procedures were
      performed endoscopically. There were 37 recurrences (25%). These patients either
      underwent a repeat endoscopic procedure or an open excision. One hundred and ten
      (75%) endoscopic procedures were successful. CONCLUSIONS: Piriform sinus tract
      anomalies often present as a mass and recurrent neck infections. This review
      reveals that treating the internal piriform sinus opening alone can be
      successful. This procedure has low morbidity, short operative time, and high
      success. We advocate this approach first with a combined open/laryngoscopic
      approach for failed cases. To our knowledge, our technique of CO2laser ablation
      of the tract followed by suture closure has not been previously described. We
      believe this to be the first comprehensive review of this topic and the largest
      series of cases included in a single report.

PMID- 26215723
TI  - 4K Video-Laryngoscopy and Video-Stroboscopy: Preliminary Findings.
AB  - INTRODUCTION: 4K video is a new format. At 3840 * 2160 resolution, it has 4 times
      the resolution of standard 1080 high definition (HD) video. Magnification can be
      done without loss of resolution. This study uses 4K video for video-stroboscopy.
      MATERIAL AND METHOD: Forty-six patients were examined by conventional video
      stroboscopy (digital 3 chip CCD) and compared with 4K video-stroboscopy. The
      video was recorded on a Blackmagic 4K cinema production camera in CinemaDNG RAW
      format. The video was played back on a 4K monitor and compared to standard video.
      Pathological conditions included: polyps, scar, cysts, cancer, sulcus, and
      nodules. RESULTS: Successful 4K video recordings were achieved in all subjects
      using a 70 degrees  rigid endoscope. The camera system is bulky. The examination
      is performed similarly to standard video-stroboscopy. Playback requires a 4K
      monitor. As expected, the images were far clearer in detail than standard video.
      Stroboscopy video using the 4K camera was consistently able to show more detail.
      Two patients had diagnosis change after 4K viewing. CONCLUSION: 4K video is an
      exciting new technology that can be applied to laryngoscopy. It allows for
      cinematic 4K quality recordings. Both continuous and stroboscopic light can be
      used for visualization. Its clinical utility is feasible, but usefulness must be
      proven.

PMID- 26215724
TI  - Endoscopic Assessment of Swallowing After Prolonged Intubation in the ICU
      Setting.
AB  - OBJECTIVES: The purpose of this study was to identify the frequency of swallowing
      dysfunction after extubation in a sample of patients with no preexisting
      dysphagia. METHODS: Mechanically ventilated patients in the ICU with no prior
      history of dysphagia received a flexible endoscopic evaluation of swallowing
      (FEES) exam within 72 hours after extubation. The FEES was then analyzed for
      variables related to swallowing patterns and laryngeal pathology. Univariate
      analyses were performed to identify relationships between variables. RESULTS:
      Fifty-nine patients were included in this study. After extubation, 21 (35.6%)
      penetrated and 13 (22.0%) aspirated. The mean days intubated was 9.4 +/- 6.1.
      Various forms of laryngeal injury were associated with worse swallowing scores,
      and delayed onset of the swallow was a common finding in all patients post
      extubation. Of the 44 participants evaluated <= 24 hours post extubation, 56.8%
      penetrated/aspirated. Of the 15 patients evaluated >24 hours post extubation,
      60.0% penetrated/aspirated. CONCLUSIONS: This study found a high frequency of
      dysphagia after prolonged intubation in patients with no preexisting dysphagia.
      Important variables leading to dysphagia are often overlooked, such as swallowing
      delay and laryngeal pathology. The timing of swallowing assessments did not
      reveal any difference in dysphagia frequency, suggesting that it might not be
      necessary to wait to perform dysphagia screens or evaluations.

PMID- 26215725
TI  - Intraoperative Ultrasonography During Transoral Robotic Surgery.
AB  - OBJECTIVE: This study describes the potential application of intraoperative
      ultrasound imaging during transoral robotic surgery (TORS). METHODS: Ultrasound
      imaging was performed during transoral robotic resection of oropharyngeal tumors
      in 10 patients at a tertiary academic center. Ultrasound imaging was utilized to
      identify large-caliber vessels adjacent to the surgical site. Measurements were
      also taken on the ultrasound of tumor thickness to determine the deep margin.
      Following resection, the tumor was sectioned, and a gross measurement of the
      tumor thickness was obtained. RESULTS: Intraoperative ultrasound use led to the
      identification of larger-caliber blood vessels within the operative field prior
      to encountering them visually. Ultrasound could also aid in defining deep tumor
      margins; the tumor thickness measured via ultrasound was found to be accurate
      within 1 to 2 mm of the grossly measured tumor thickness. This allowed for
      focused, careful dissection to protect and avoid blood vessels during dissection
      as well as improved tumor resection. CONCLUSIONS: The use of intraoperative
      ultrasound provides additional information to the head and neck surgeon during
      TORS. This may be used to identify blood vessels and assess tumor margins,
      thereby improving the safety and efficacy of TORS.

PMID- 26215726
TI  - Trends in Inpatient Pediatric Polysomnography for Laryngomalacia and Craniofacial
      Anomalies.
AB  - OBJECTIVE: Increasingly, laryngomalacia and craniofacial anomalies are recognized
      as risk factors for obstructive sleep apnea. We sought to determine whether
      children with these diagnoses have become more likely to undergo inpatient
      polysomnogram (PSG) over time and to identify evolving trends in PSG utilization.
      METHODS: Retrospective analysis of the Kids' Inpatient Database from 2003 to
      2012. Children <21 years who underwent PSG were included. Weighted comparisons of
      clinical/demographic characteristics of patients undergoing PSG were performed,
      as were associations between clinical and demographic patient characteristics and
      performance of inpatient PSG. RESULTS: Between 2003 and 2012, PSG procedures
      decreased from 1266 to 829 (P < .001). Among children who underwent PSG, mean age
      decreased from 3.9 +/- 5.1 to 3.1 +/- 5.2 years (P = .001), and the frequency of
      age <1 year increased from 47.8% to 59.5% (P < .001). The frequency of
      laryngomalacia increased from 2.5% to 14.3% (P < .001), while the frequency of
      craniofacial anomalies increased from 6.2% to 19.4% (P < .001). Laryngomalacia
      and craniofacial anomalies were predictive of undergoing inpatient PSG in both
      timeframes. CONCLUSION: Despite decreasing PSG volumes, diagnoses of
      laryngomalacia and craniofacial anomalies comprised increasing fractions of
      children undergoing inpatient PSG between 2003 and 2012. Laryngomalacia and
      craniofacial anomalies were also predictive of inpatient PSG use in both
      timeframes.

PMID- 26215727
TI  - Nonparametric inference for time-dependent incremental cost-effectiveness ratios.
AB  - As the costs of medical care increase, more studies are evaluating cost in
      addition to effectiveness of treatments. Cost-effectiveness analyses in
      randomized clinical trials have typically been conducted only at the end of
      follow-up. However, cost-effectiveness may change over time. We therefore propose
      a nonparametric estimator to assess the incremental cost-effectiveness ratio over
      time. We also derive the asymptotic variance of our estimator and present
      formulation of Fieller-based simultaneous confidence bands. Simulation studies
      demonstrate the performance of our point estimators, variance estimators, and
      confidence bands. We also illustrate our methods using data from a randomized
      clinical trial, the second Multicenter Automatic Defibrillator Implantation
      Trial. This trial studied the effects of implantable cardioverter-defibrillators
      on patients at high risk for cardiac arrhythmia. Results show that our estimator
      performs well in large samples, indicating promising future directions in the
      field of cost-effectiveness. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26215729
TI  - Pathogenesis of IgE-mediated food allergy.
AB  - Food allergy is a prevalent disease for which there is no current treatment
      beyond careful food avoidance. Accidental exposure to foods causes reactions in
      allergic individuals that can range in severity from mild skin reactions to
      severe and life-threatening anaphylaxis, and there are no validated tools to
      predict severity of reactions. A greater understanding of the pathogenesis of
      food allergy is needed to develop prevention and treatment strategies for food
      allergy. In the last few years, there have been significant developments in the
      field of food allergy that have led to new ideas about food allergy prevention,
      diagnosis, and treatment. This review will discuss these recent advances in the
      food allergy field as well as identify gaps in our knowledge about the immune
      mechanisms of allergy and tolerance to foods. 

PMID- 26215728
TI  - Hemagglutinin-esterase-fusion (HEF) protein of influenza C virus.
AB  - Influenza C virus, a member of the Orthomyxoviridae family, causes flu-like
      disease but typically only with mild symptoms. Humans are the main reservoir of
      the virus, but it also infects pigs and dogs. Very recently, influenza C-like
      viruses were isolated from pigs and cattle that differ from classical influenza C
      virus and might constitute a new influenza virus genus. Influenza C virus is
      unique since it contains only one spike protein, the hemagglutinin-esterase
      fusion glycoprotein HEF that possesses receptor binding, receptor destroying and
      membrane fusion activities, thus combining the functions of Hemagglutinin (HA)
      and Neuraminidase (NA) of influenza A and B viruses. Here we briefly review the
      epidemiology and pathology of the virus and the morphology of virus particles and
      their genome. The main focus is on the structure of the HEF protein as well as on
      its co- and post-translational modification, such as N-glycosylation, disulfide
      bond formation, S-acylation and proteolytic cleavage into HEF1 and HEF2 subunits.
      Finally, we describe the functions of HEF: receptor binding, esterase activity
      and membrane fusion. 

PMID- 26215730
TI  - Bevacizumab promotes venous thromboembolism through the induction of PAI-1 in a
      mouse xenograft model of human lung carcinoma.
AB  - BACKGROUND: An increased incidence of venous thromboembolism (VTE) is associated
      with anti-vascular endothelial growth factor (VEGF) treatment in cancer. However,
      the mechanism underlying this effect remains elusive. In this study, we examined
      the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A, on VTE
      in a murine xenograft A549 cell tumor model. METHODS: Inferior vena cava stenosis
      model and FeCl3-induced saphenous vein thrombosis model were performed in a mouse
      xenograft models of human lung adenocarcinoma. RESULTS: We found that treatment
      with bevacizumab significantly increased the thrombotic response to inferior vena
      cava obstruction and femoral vein injury. Plasminogen activator inhibitor (PAI-1)
      expression in tumors, plasma, and thrombi was significantly increased by
      bevacizumab. However, bevacizumab did not enhance VTE in PAI-1-deficient mice,
      suggesting that PAI-1 is a major mediator of bevacizumab's prothrombotic effect.
      VEGF inhibited expression of PAI-1 by A549 cells, and this effect was neutralized
      by bevacizumab, suggesting that bevacizumab increases PAI-1 expression in vivo by
      blocking the inhibitory effect of VEGF on PAI-1 expression by tumor cells.
      Pharmacological inhibition of PAI-1 with PAI-039 blocked bevacizumab-induced
      venous thrombosis. CONCLUSION: Collectively, these findings indicate that PAI-1
      plays a role in VTE associated with antiangiogenic therapy and the inhibition of
      PAI-1 shows efficacy as a therapeutic strategy for the prevention of bevacizumab
      associated VTE.

PMID- 26215731
TI  - Tailored e-Health services for the dementia care setting: a pilot study of
      'eHealthMonitor'.
AB  - BACKGROUND: The European eHealthMonitor project (eHM) developed a user-sensitive
      and interactive web portal for dementia care: the eHM Dementia Portal (eHM-DP).
      It aims to provide targeted and personalized support for informal caregivers of
      people with dementia in a home-based care setting. The objective of the pilot
      study was to obtain feedback on the eHM-DP from two user perspectives (caregivers
      and medical professionals), focusing on caregiver empowerment, decision aid, and
      the perceived benefits of the eHM-DP. METHODS: The study on the eHM-DP was
      conducted from March 2014 to June 2014. The methodological approach followed a
      user-participatory design with a total number of 42 participants. The study
      included caregivers of people with dementia and medical professionals (MPs) from
      the metropolitan region of Erlangen-Nurnberg (Bavaria, Germany). Study
      participants were interviewed face-to-face with semi-structured, written
      interviews. RESULTS: Caregivers indicated a high degree of perceived support by
      the eHM-DP and of provided decision aid. In total, 89 % of caregivers and 54 % of
      MPs would use the eHM-DP if access were provided. The primary benefits
      participants perceived were the acquisition of individualized information,
      computerized interaction between caregivers and MPs, empowerment in health
      related decisions and comprehensive insights into the progress of the disease.
      Major recommendations for improving the eHM-DP encompassed: an active search
      functionality based on predefined terms, the implementation of a chatroom for
      caregivers, an upload function and alerts for MPs, as well as the overall design.
      CONCLUSIONS: Our study is the first to have provided new insights and results on
      an interactive and needs-oriented web portal, endeavouring towards empowerment
      and assistance in decision making for caregivers as well as MPs within the realm
      of caring for patients with dementia. The acceptance and willingness to use the
      eHM-DP emphasizes the potential of eHealth services for community-based dementia
      care settings.

PMID- 26215732
TI  - Attempting to bridge the 10/90 divide: special issue on South Asian mental
      health.

PMID- 26215733
TI  - Quantitative NMRI and NMRS identify augmented disease progression after loss of
      ambulation in forearms of boys with Duchenne muscular dystrophy.
AB  - Quantitative NMRI and (31)P NMRS indices are reported in the forearms of 24
      patients with Duchenne muscular dystrophy (DMD) (6-18 years, 14 non-ambulant)
      amenable to exon 53 skipping therapy and in 12 age-matched male controls (CONT).
      Examinations carried out at 3 T comprised multi-slice 17-echo measurements of
      muscle water T2 and heterogeneity, three-point Dixon imaging of fat fraction in
      flexor and extensor muscles (FLEX, EXT), and non-localised spectroscopy of
      phosphate metabolites. We studied four imaging indices, eight metabolic ratios
      combining ATP, phosphocreatine, phosphomonoesters and phosphodiesters, the
      cytosolic inorganic phosphate (Pia ) and an alkaline (Pib) pool present in
      dystrophic muscle, and average pH. All indices differed between DMD and CONT,
      except for muscle water T2 . Measurements were outside the 95th percentile of age
      matched CONT values in over 65% of cases for percentage fat signal (%F), and in
      78-100% of cases for all spectroscopic indices. T2 was elevated in one-third of
      FLEX measurements, whereas %pixels > 39 ms and T2 heterogeneity were abnormal in
      one-half of the examinations. The FLEX muscles had higher fat infiltration and T2
      than EXT muscle groups. All indices, except pH, correlated with patient age,
      although the correlation was negative for T2 . However, in non-ambulant patients,
      the correlation with years since loss of ambulation was stronger than the
      correlation with age, and the slope of evolution per year was steeper after loss
      of ambulation. All indices except Pi/gATP differed between ambulant and non
      ambulant patients; however, T2 and %pixels > 39 ms were highest in ambulant
      patients, possibly owing to the greater extent of inflammatory processes earlier
      in the disease. All other indices were worse in non-ambulant subjects.
      Quantitative measurements obtained from patients at different disease stages
      covered a broad range of abnormalities that evolved with the disease, and
      metabolic indices were up to 10-fold above normal from the onset, thus
      establishing a variety of potential markers for future therapy.

PMID- 26215734
TI  - Protein function prediction using guilty by association from interaction
      networks.
AB  - Protein function prediction from sequence using the Gene Ontology (GO)
      classification is useful in many biological problems. It has recently attracted
      increasing interest, thanks in part to the Critical Assessment of Function
      Annotation (CAFA) challenge. In this paper, we introduce Guilty by Association on
      STRING (GAS), a tool to predict protein function exploiting protein-protein
      interaction networks without sequence similarity. The assumption is that whenever
      a protein interacts with other proteins, it is part of the same biological
      process and located in the same cellular compartment. GAS retrieves interaction
      partners of a query protein from the STRING database and measures enrichment of
      the associated functional annotations to generate a sorted list of putative
      functions. A performance evaluation based on CAFA metrics and a fair comparison
      with optimized BLAST similarity searches is provided. The consensus of GAS and
      BLAST is shown to improve overall performance. The PPI approach is shown to
      outperform similarity searches for biological process and cellular compartment GO
      predictions. Moreover, an analysis of the best practices to exploit protein
      protein interaction networks is also provided. 

PMID- 26215735
TI  - Non-enzymatic glycation of alpha-crystallin as an in vitro model for aging,
      diabetes and degenerative diseases.
AB  - Alpha crystallin, a small heat-shock protein, has been studied extensively for
      its chaperone function. Alpha crystallin subunits are expressed in stress
      conditions and have been found to prevent apoptosis by inhibiting the activation
      of caspase pathway. Non-enzymatic glycation of protein leads to the formation of
      advanced glycation end-products (AGEs). These AGEs bind to receptors and lead to
      blocking the signaling pathways or cause protein precipitation as observed in
      aggregation-related diseases. Methylglyoxal (MGO) is one of the major glycating
      agents expressed in pathological conditions due to defective glycolysis pathway.
      MGO reacts rapidly with proteins, forms AGEs and finally leads to aggregation.
      The goal of this study was to understand the non-enzymatic glycation-induced
      structural damage in alpha crystallin using biophysical and spectroscopic
      characterization. This will help to develop better disease models for
      understanding the biochemical pathways and also in drug discovery. 

PMID- 26215736
TI  - Preinduction of heat shock protein 70 protects mice against post-infection
      irritable bowel syndrome via NF-kappaB and NOS/NO signaling pathways.
AB  - This study aimed to investigate the protective effects of preinduction of heat
      shock protein 70 (HSP70) on Trichinella spiralis infection-induced post
      infectious irritable bowel syndrome (PI-IBS) in mice. Trichinella spiralis
      infection significantly reduced HSP70 abundance, ileal villus height and crypt
      depth, expression of tight junctions, serum lysine and arginine concentrations,
      and ileal SCL7A6 and SCL7A7 mRNA levels, induced inflammatory response, and
      activated NF-kappaB signaling pathway. Meanwhile, the heat treatment upregulated
      HSP70 expression, and then reversed intestinal dysfunction and inflammatory
      response. Preinduction of HSP70 enhanced serum arginine and intestinal SCL7A7
      expression and inhibited NF-kappaB activation compared with PI-IBS model.
      Treatment with pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor) and N
      nitro-L-arginine methyl ester hydrochloride (L-NAME, a nitric oxide synthase
      inhibitor, NOS) further demonstrated that preinduction of HSP70 might inhibit NF
      kappaB and activated NOS/nitric oxide (NO) signaling pathways. In conclusion,
      preinduction of HSP70 by heat treatment may confer beneficial effects on
      Trichinella spiralis infection-induced PI-IBS in mice, and the protective effect
      of HSP70 may be associated with inhibition of NF-kappaB and stimulation of NOS/NO
      signaling pathways. 

PMID- 26215738
TI  - Bilateral microphthalmos with cyst in a neonatal foal.
AB  - A 1-day-old miniature horse filly was presented to the University of Florida
      Veterinary Ophthalmology service for evaluation of multiple ocular anomalies
      which were present from birth. Protruding from the right orbit was a large,
      fluctuant, red, dry and variably ulcerated mass. A globe could not be appreciated
      clinically in the left orbit. Ocular ultrasound of both orbits was performed.
      This revealed a lobular, hypo-echoic structure filling the right orbit, with
      multiple hyperechoic septations; normal ocular structures were not identified.
      Ultrasound of the left orbit revealed a microphthalmic eye, with a well-defined,
      hyperechoic structure in the vitreous that was thought to be the lens. Due to
      irreversible blindness, the foal was humanely euthanized. Histopathology and
      immunohistochemistry of the orbital contents revealed bilateral microphthalmos
      with cyst, a congenital defect rarely reported in the veterinary literature.

PMID- 26215737
TI  - Hypomorphic variants of cationic amino acid transporter 3 in males with autism
      spectrum disorders.
AB  - Cationic amino acid transporters (CATs) mediate the entry of L-type cationic
      amino acids (arginine, ornithine and lysine) into the cells including neurons.
      CAT-3, encoded by the SLC7A3 gene on chromosome X, is one of the three CATs
      present in the human genome, with selective expression in brain. SLC7A3 is highly
      intolerant to variation in humans, as attested by the low frequency of
      deleterious variants in available databases, but the impact on variants in this
      gene in humans remains undefined. In this study, we identified a missense variant
      in SLC7A3, encoding the CAT-3 cationic amino acid transporter, on chromosome X by
      exome sequencing in two brothers with autism spectrum disorder (ASD). We then
      sequenced the SLC7A3 coding sequence in 148 male patients with ASD and identified
      three additional rare missense variants in unrelated patients. Functional
      analyses of the mutant transporters showed that two of the four identified
      variants cause severe or moderate loss of CAT-3 function due to altered protein
      stability or abnormal trafficking to the plasma membrane. The patient with the
      most deleterious SLC7A3 variant had high-functioning autism and epilepsy, and
      also carries a de novo 16p11.2 duplication possibly contributing to his
      phenotype. This study shows that rare hypomorphic variants of SLC7A3 exist in
      male individuals and suggest that SLC7A3 variants possibly contribute to the
      etiology of ASD in male subjects in association with other genetic factors. 

PMID- 26215739
TI  - Generalized seizures and transient contralateral hemiparesis following
      retrobulbar anesthesia: a case report.
AB  - BACKGROUND: Retrobulbar block is a local anesthetic technique widely used for
      intraocular surgery. Although retrobulbar anesthesia is considered to be
      relatively safe, a number of serious adverse events have been reported. To our
      knowledge, immediate onset of generalized seizures with contralateral hemiparesis
      after retrobulbar anesthesia has not been reported. CASE PRESENTATION: A 62-year
      old Caucasian healthy male with a right eye retinal detachment was admitted for
      pars plana vitrectomy. During retrobulbar anesthesia with ropivacaine and before
      needle withdrawal, the patient developed twitching of the face which rapidly
      progressed to generalized tonic-clonic seizures. Arterial oxygen saturation
      decreased to 75 %. Chin lift was performed and 100 % oxygen was administrated via
      face mask, which increased saturation to 99 %. Midazolam 2 mg was administrated
      intravenously to control seizures. After cessation of seizures, left-sided
      hemiparesis was evident. Brain computed tomography and electroencephalogram were
      normal 3 h later. The patient underwent pars plana vitrectomy under general
      anesthesia 4 days later. CONCLUSION: Serious complications of local anesthesia
      for ophthalmic surgery are uncommon. We present a case in which generalized tonic
      clonic seizures developed during retrobulbar anesthesia, followed by transient
      contralateral hemiparesis. The early onset of seizures indicated intra-arterial
      injection of the anesthetic. Our case suggested the need for close monitoring
      during the performance of retrobulbar anesthesia and the presence of well-trained
      personnel for early recognition and immediate management of the complications.

PMID- 26215740
TI  - The availability of over-the-counter codeine medicines across the European Union.

PMID- 26215741
TI  - Topological analysis of the Na+/H+ exchanger.
AB  - The mammalian Na+/H+ exchanger isoform 1 (NHE1) is a ubiquitously expressed
      integral membrane protein present in mammalian cells. It is made up of a
      hydrophobic 500 amino acid membrane domain that transports and removes protons
      from within cells, and a regulatory intracellular cytosolic domain made of
      approximately 315 amino acids. Determining the structure of NHE1 is critical for
      both an understanding of the Na+/H+ exchange mechanism of transport, and in the
      design of new improved inhibitors for use in treatment of several diseases in
      which it is involved. Differing models of the NHE1 protein have been proposed.
      The first model suggested by two groups proposes that amino acids 1-500 form a 12
      transmembrane segment spanning region in which amino acids 1-127 form two
      transmembrane segments, and amino acids 315-411 form a single transmembrane
      segment with membrane associated segments. A second model based on the structure
      of the Escherichia coli Na+/H+ exchanger protein proposes an overall similar
      topology, but suggests amino acids 1-127 are removed as a signal sequence and are
      not present in the mature protein. It also suggests a different topology of amino
      acids 315-411 to form three transmembrane segments. We used cysteine scanning
      accessibility and examination of glycosylation of the mature protein to
      characterize the NHE1 protein. Our results demonstrate that the model of NHE1 is
      correct which suggests that amino acids 1-127 form two transmembrane segments
      that remain connected to the mature protein, and the segment between amino acids
      315-411 is one transmembrane segment.

PMID- 26215743
TI  - Membrane-mediated amyloid formation of PrP 106-126: A kinetic study.
AB  - PrP 106-126 conserves the pathogenic and physicochemical properties of the
      Scrapie isoform of the prion protein. PrP 106-126 and other amyloidal proteins
      are capable of inducing ion permeability through cell membranes, and this
      property may represent the common primary mechanism of pathogenesis in the
      amyloid-related degenerative diseases. However, for many amyloidal proteins,
      despite numerous phenomenological observations of their interactions with
      membranes, it has been difficult to determine the molecular mechanisms by which
      the proteins cause ion permeability. One approach that has not been undertaken is
      the kinetic study of protein-membrane interactions. We found that the reaction
      time constant of the interaction between PrP 106-126 and membranes is suitable
      for such studies. The kinetic experiment with giant lipid vesicles showed that
      the membrane area first increased by peptide binding but then decreased. The
      membrane area decrease was coincidental with appearance of extramembranous
      aggregates including lipid molecules. Sometimes, the membrane area would increase
      again followed by another decrease. The kinetic experiment with small vesicles
      was monitored by circular dichroism for peptide conformation changes. The results
      are consistent with a molecular simulation following a simple set of well-defined
      rules. We deduced that at the molecular level the formation of peptide amyloids
      incorporated lipid molecules as part of the aggregates. Most importantly the
      amyloid aggregates desorbed from the lipid bilayer, consistent with the
      macroscopic phenomena observed with giant vesicles. Thus we conclude that the
      main effect of membrane-mediated amyloid formation is extraction of lipid
      molecules from the membrane. We discuss the likelihood of this effect on membrane
      ion permeability. 

PMID- 26215742
TI  - Ceramide channels: destabilization by Bcl-xL and role in apoptosis.
AB  - Ceramide is a bioactive sphingolipid involved in mitochondrial-mediated
      apoptosis. Our data suggest that ceramides directly regulate a key initiation
      step in apoptosis: mitochondrial outer membrane permeabilization (MOMP). MOMP
      allows release of intermembrane space proteins to the cytosol, inducing the
      execution of the cell. Ceramides form channels in planar phospholipid membranes
      and outer membranes of isolated mitochondria, channels large enough to facilitate
      passage of proteins released during MOMP. Bcl-xL inhibits MOMP in vivo and
      inhibits the formation of ceramide channels in vitro. However the significance of
      Bcl-xL's regulation of ceramide channel formation within cells was untested. We
      engineered Bcl-xL point mutations that specifically affect the interaction
      between ceramide and Bcl-xL to probe the mechanism of ceramide channel regulation
      and the role of ceramide channels in apoptosis. Using these mutants and
      fluorescently-labeled ceramide, we identified the hydrophobic groove on Bcl-xL as
      the critical ceramide binding site and regulator of ceramide channel formation.
      Bcl-xL mutants with weakened interaction with ceramide also have reduced ability
      to interfere with ceramide channel formation. Some mutants have similar altered
      ability to inhibit both ceramide and Bax channel formation, whereas others act
      differentially, suggesting distinct but overlapping binding sites. To probe the
      relative importance of these channels in apoptosis, Bcl-xL mutant proteins were
      stably expressed in Bcl-xL deficient cells. Weakening the inhibition of either
      Bax or ceramide channels decreased the ability of Bcl-xL to protect cells from
      apoptosis in a stimulus-dependent manner. These studies provide the first in vivo
      evidence for the role of ceramide channels in MOMP. 

PMID- 26215744
TI  - Impure placebo is a useless concept.
AB  - Placebos are allegedly used widely in general practice. Surveys reporting high
      level usage, however, have combined two categories, 'pure' and 'impure' placebos.
      The wide use of placebos is explained by the high level usage of impure placebos.
      In contrast, the prevalence of the use of pure placebos has been low. Traditional
      pure placebos are clinically ineffective treatments, whereas impure placebos form
      an ambiguous group of diverse treatments that are not always ineffective. In this
      paper, we focus on the impure placebo concept and demonstrate problems related to
      it. We also show that the common examples of impure placebos are not meaningful
      from the point of view of clinical practice. We conclude that the impure placebo
      is a scientifically misleading concept and should not be used in scientific or
      medical literature. The issues behind the concept, however, deserve serious
      attention in future research. 

PMID- 26215746
TI  - Transmembrane protein 106a activates mouse peritoneal macrophages via the MAPK
      and NF-kappaB signaling pathways.
AB  - The M1 and M2 states of macrophage are the two extremes of a
      physiologic/phenotypic continuum that is dynamically influenced by environmental
      signals. Molecular mechanism analysis indicated that they gain M1 and M2-related
      functions after encountering specific ligands in the tissue environment. Here, we
      first characterized the previously unknown immunobiological functions of mouse
      Tmem106a. This protein is abundantly expressed on the surface of mouse
      macrophages. Activation of Tmem106a by stimulation with anti-Tmem106a upregulated
      the expression of CD80, CD86, CD69 and MHC II on macrophage, and induced the
      release of TNF-alpha, IL-1beta, IL-6, CCL2 and NO, but not IL-10. These effects
      were largely abrogated by pretreatment with siRNA against Tmem106a. Notably, anti
      Tmem106a significantly increased iNOS production and phosphorylation of STAT1,
      and had no effect on the ARGINASE-1 or p-STAT6 level, indicating that anti
      Tmem106a activated macrophages and polarized them into M1-like macrophages.
      Further analysis found that anti-Tmem106a stimulation increased phosphorylation
      of ERK-1/2, JNK, p38 MAPK, NF-kappaB p65 and IKKalpha/beta, and promoted nuclear
      translocation of the cytosolic NF-kappaB p65 subunit. Collectively, these data
      suggest that mouse Tmem106a might be a new trigger of macrophage activation and
      have some influence toward the M1 state through the activation of the MAPKs and
      NF-kappaB pathway. 

PMID- 26215747
TI  - Viscoelastic point-of-care testing to assist with the diagnosis, management and
      monitoring of haemostasis: a systematic review and cost-effectiveness analysis.
AB  - BACKGROUND: Patients with substantive bleeding usually require transfusion and/or
      (re-)operation. Red blood cell (RBC) transfusion is independently associated with
      a greater risk of infection, morbidity, increased hospital stay and mortality.
      ROTEM (ROTEM(r) Delta, TEM International GmbH, Munich, Germany; www.rotem.de),
      TEG (TEG(r) 5000 analyser, Haemonetics Corporation, Niles, IL, USA;
      www.haemonetics.com) and Sonoclot (Sonoclot(r) coagulation and platelet function
      analyser, Sienco Inc., Arvada, CO) are point-of-care viscoelastic (VE) devices
      that use thromboelastometry to test for haemostasis in whole blood. They have a
      number of proposed advantages over standard laboratory tests (SLTs): they provide
      a result much quicker, are able to identify what part of the clotting process is
      disrupted, and provide information on clot formation over time and fibrinolysis.
      OBJECTIVES: This assessment aimed to assess the clinical effectiveness and cost
      effectiveness of VE devices to assist with the diagnosis, management and
      monitoring of haemostasis disorders during and after cardiac surgery, trauma
      induced coagulopathy and post-partum haemorrhage (PPH). METHODS: Sixteen
      databases were searched to December 2013: MEDLINE (OvidSP), MEDLINE In-Process
      and Other Non-Indexed Citations and Daily Update (OvidSP), EMBASE (OvidSP),
      BIOSIS Previews (Web of Knowledge), Science Citation Index (SCI) (Web of
      Science), Conference Proceedings Citation Index (CPCI-S) (Web of Science),
      Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of
      Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE),
      Health Technology Assessment (HTA) database, Latin American and Caribbean Health
      Sciences Literature (LILACS), International Network of Agencies for Health
      Technology Assessment (INAHTA), National Institute for Health Research (NIHR) HTA
      programme, Aggressive Research Intelligence Facility (ARIF), Medion, and the
      International Prospective Register of Systematic Reviews (PROSPERO). Randomised
      controlled trials (RCTs) were assessed for quality using the Cochrane Risk of
      Bias tool. Prediction studies were assessed using QUADAS-2. For RCTs, summary
      relative risks (RRs) were estimated using random-effects models. Continuous data
      were summarised narratively. For prediction studies, the odds ratio (OR) was
      selected as the primary effect estimate. The health-economic analysis considered
      the costs and quality-adjusted life-years of ROTEM, TEG and Sonoclot compared
      with SLTs in cardiac surgery and trauma patients. A decision tree was used to
      take into account short-term complications and longer-term side effects from
      transfusion. The model assumed a 1-year time horizon. RESULTS: Thirty-one studies
      (39 publications) were included in the clinical effectiveness review. Eleven RCTs
      (n=1089) assessed VE devices in patients undergoing cardiac surgery; six assessed
      thromboelastography (TEG) and five assessed ROTEM. There was a significant
      reduction in RBC transfusion [RR 0.88, 95% confidence interval (CI) 0.80 to 0.96;
      six studies], platelet transfusion (RR 0.72, 95% CI 0.58 to 0.89; six studies)
      and fresh frozen plasma to transfusion (RR 0.47, 95% CI 0.35 to 0.65; five
      studies) in VE testing groups compared with control. There were no significant
      differences between groups in terms of other blood products transfused.
      Continuous data on blood product use supported these findings. Clinical outcomes
      did not differ significantly between groups. There were no apparent differences
      between ROTEM or TEG; none of the RCTs evaluated Sonoclot. There were no data on
      the clinical effectiveness of VE devices in trauma patients or women with PPH. VE
      testing was cost-saving and more effective than SLTs. For the cardiac surgery
      model, the cost-saving was L43 for ROTEM, L79 for TEG and L132 for Sonoclot. For
      the trauma population, the cost-savings owing to VE testing were more
      substantial, amounting to per-patient savings of L688 for ROTEM compared with
      SLTs, L721 for TEG, and L818 for Sonoclot. This finding was entirely dependent on
      material costs, which are slightly higher for ROTEM. VE testing remained cost
      saving following various scenario analyses. CONCLUSIONS: VE testing is cost
      saving and more effective than SLTs, in both patients undergoing cardiac surgery
      and trauma patients. However, there were no data on the clinical effectiveness of
      Sonoclot or of VE devices in trauma patients. STUDY REGISTRATION: This study is
      registered as PROSPERO CRD42013005623. FUNDING: The NIHR Health Technology
      Assessment programme.

PMID- 26215748
TI  - Cost-effectiveness of 40-hour versus 100-hour vocational rehabilitation on work
      participation for workers on sick leave due to subacute or chronic
      musculoskeletal pain: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Although vocational rehabilitation is a widely advocated intervention
      for workers on sick leave due to subacute or chronic nonspecific musculoskeletal
      pain, the optimal dosage of effective and cost-effective vocational
      rehabilitation remains unknown. The objective of this paper is to describe the
      design of a non-inferiority trial evaluating the effectiveness and cost
      effectiveness of 40-h multidisciplinary vocational rehabilitation compared with
      100-h multidisciplinary vocational rehabilitation on work participation for
      workers on sick leave due to subacute or chronic musculoskeletal pain.
      METHODS/DESIGN: A non-inferiority study design will be applied. The study
      population consists of workers who are on part-time or full-time sick leave due
      to subacute or chronic nonspecific musculoskeletal pain. Two multidisciplinary
      vocational rehabilitation programs following the bio-psychosocial approach will
      be evaluated in this study: 40-h vocational rehabilitation and 100-h vocational
      rehabilitation, both delivered over a maximum of 15 weeks. The 100-h vocational
      rehabilitation comprises five modules: work participation coordination, graded
      activity, cognitive behavioral therapy, group education, and relaxation. The 40-h
      vocational rehabilitation comprises work participation coordination and a well
      reasoned choice from the other four modules. Four rehabilitation centers will
      participate in this study, each delivering both interventions. Patients will be
      randomized into one of the interventions, stratified for the duration of sick
      leave (<6 weeks or >= 6 weeks) and type of sick leave (part-time or full-time).
      The primary outcome is work participation, measured by self-reported sick leave
      days, and will be assessed at baseline, mid-term, discharge, and at 2, 4, 6, 8,
      10, and 12 months follow-up. Secondary outcomes are work ability, disability,
      quality of life, and physical functioning and will be assessed at baseline,
      discharge, and at 6 and 12 months follow-up. Cost outcomes are absenteeism,
      presenteeism, healthcare usage, and travelling costs. Cost-effectiveness will be
      evaluated from the societal and employer perspectives. DISCUSSION: The results
      obtained from this study will be useful for vocational rehabilitation practice
      and will provide stakeholders with relevant insights into two versions of
      vocational rehabilitation. TRIAL REGISTRATION: Dutch Trial Register identifier:
      NTR4362 (registered 17 March 2014).

PMID- 26215749
TI  - True targeting-derived prostate biopsy: HistoScanningTM remained inadequate
      despite advanced technical efforts.
AB  - PURPOSE: To verify the reliability of HistoScanningTM-based, true targeting (TT)
      derived prostate biopsy. METHODS: We relied on 40 patients suspicious for
      prostate cancer who underwent standard and TT-derived prostate biopsy.
      Sensitivity, specificity, positive predictive value, negative predictive value
      and the area under the curve (AUC) were assessed for the prediction of biopsy
      results per octant by HistoScanningTM, using different HistoScanningTM signal
      volume cutoffs (>0, >0.2 and >0.5 ml). RESULTS: Overall, 319 octants were
      analyzed. Of those, 64 (20.1 %) harbored prostate cancer. According to different
      HistoScanningTM signal volume cutoffs (>0, >0.2 and >0.5 ml), the AUCs for
      predicting biopsy results were: 0.51, 0.51 and 0.53, respectively. Similarly, the
      sensitivity, specificity, positive predictive and negative predictive values
      were: 20.7, 78.2, 17.4 and 81.6 %; 20.7, 82.0, 20.3 and 82.3 %; and 12.1, 94.6,
      33.3 and 82.9 %, respectively. CONCLUSIONS: Prediction of biopsy results based on
      HistoScanningTM signals and TT-derived biopsies was unreliable. Moreover, the AUC
      of TT-derived biopsies was low and did not improve when additional signal volume
      cutoffs were applied (>0.2 and >0.5 ml). We cannot recommend a variation of well
      established biopsy standards or reduction in biopsy cores based on
      HistoScanningTM signals.

PMID- 26215750
TI  - Histologic subtype impacts cancer-specific survival in patients with sarcomatoid
      variant renal cell carcinoma treated surgically.
AB  - PURPOSE: To report survival outcomes of patients treated surgically for
      sarcomatoid-variant renal cell carcinomas (sRCC) and to assess whether the
      underlying histologic subtype is an independent predictor of outcome. METHODS:
      One hundred and fifty-one patients underwent surgery at a referral center between
      1991 and 2014 and had sRCC in final pathology. Kaplan-Meier curves for metastasis
      free survival and cancer-specific survival (CSS) were calculated, and the log
      rank test assessed differences between clear cell sRCC and nonclear cell sRCC.
      Cox regression models were generated to test the prognostic value of histologic
      subtype. RESULTS: Of 151 patients, 120 (79 %) had clear cell sRCC and 31 (21 %)
      had nonclear cell sRCC. Ninety-eight (65 %) patients had M0/Mx disease at
      presentation. Among those M0/Mx patients, metastasis-free survival probabilities
      were 49 % at 2 years [95 % confidence interval (CI) 38-60] and 39 % at 5 years
      (95 % CI 28-50), while CSS probabilities were 50 % at 2 years (95 % CI 41-58) and
      32 % at 5 years (95 % CI 24-41). There was no significant difference in
      metastasis-free survival between clear cell and nonclear cell sRCC (p = 0.8).
      However, patients with nonclear cell sRCC had significantly lower CSS than
      patients with clear cell sRCC (p = 0.035). In multivariable analyses, nonclear
      cell sRCC conferred a higher risk of cancer-specific death compared with clear
      cell sRCC (HR 2.30, 95 % CI 1.38-3.82, p = 0.001). CONCLUSIONS: In a cohort of
      patients treated surgically, the underlying histologic subtype of sRCC had an
      impact on CSS. These results present valuable information for individual
      counseling and patient selection in clinical trials.

PMID- 26215751
TI  - Is multichannel urodynamic assessment necessary before considering a surgical
      treatment of BPH? Pros and cons.
AB  - PURPOSE: Lower urinary tract symptoms (LUTS) are common in middle-aged men and
      could be consequences of multiple etiologies responsible for bladder outlet
      obstruction (BOO), detrusor underactivity (DUA) and/or overactive bladder. When
      LUTS are suggestive of BOO secondary to benign prostatic hyperplasia, a surgical
      treatment can sometimes be consider. Even if multichannel urodynamic study (UDS)
      is currently the gold standard to properly assess LUTS, its use in non-neurogenic
      men is still a matter of controversy. Here, we aim to explore the evidence
      supporting or not the use of systematic multichannel UDS before considering an
      invasive treatment in men LUTS. METHODS: The debate was presented with a "pro and
      con" structure. The "pro" side supported the systematic use of a multichannel UDS
      before considering a surgical treatment in men LUTS. The "con" side successively
      refuted the "pro" side arguments. RESULTS: The "pro" side mainly based their
      argumentation on the poor correlation of LUTS and office-based tests with BOO or
      DUA. Furthermore, since a multichannel UDS could allow selecting men that will
      most benefit of a surgical procedure, they hypothesized that such an approach
      could reduce the overall morbidity rate and cost associated with. The "con" side
      considered that, in most cases, medical history and symptoms were reliable enough
      to consider surgery. Finally, they underlined the UDS limitations and the
      frequent lack of alternative to surgery in this context. CONCLUSIONS: Randomized
      clinical trials are being conducted to compare these two approaches. Their
      results would help the urological community to override this debate.

PMID- 26215752
TI  - Modulation of Cortical Motor Evoked Potential After Stroke During Electrical
      Stimulation of the Lateral Cerebellar Nucleus.
AB  - BACKGROUND: Deep brain stimulation (DBS) targeting the dentato-thalamo-cortical
      (DTC) pathway at its origin in the lateral cerebellar nucleus (LCN) has been
      shown to enhance motor recovery in a rodent model of cortical ischemia. LCN DBS
      also yielded frequency-specific changes in motor cortex excitability in the
      normal brain, indexed by motor evoked potential (MEP) amplitude. OBJECTIVE: To
      investigate the effect of cortical stroke on cortical motor excitability in a
      rodent ischemia model and to measure the effects of LCN DBS on post-ischemia
      excitability as a function of stimulation parameters. METHODS: Adult Sprague
      Dawley rats were divided into two groups: naive and stroke, with cortical
      ischemia induced through multiple, unilateral endothelin-1 injections. All
      animals were implanted with a bipolar electrode in the LCN opposite the affected
      hemisphere. MEPs were elicited from the affected hemisphere using intracortical
      microstimulation (ICMS) techniques. Multiple LCN DBS parameters were examined,
      including isochronal stimulation at 20, 30, 50, and 100 Hz as well as a novel
      burst stimulation pattern. RESULTS: ICMS-evoked MEPs were reduced in stroke (n =
      10) relative to naive (n = 12) animals. However, both groups showed frequency
      dependent augmentation of cortical excitability in response to LCN DBS. In the
      naive group, LCN DBS increased MEPs by 22-58%, while in the stroke group, MEPs
      were enhanced by 9-41% compared to OFF-DBS conditions. CONCLUSIONS: Activation of
      the DTC pathway increases cortical excitability in both naive and post-stroke
      animals. These effects may underlie, at least partially, functional
      reorganization and therapeutic benefits associated with chronic LCN DBS in post
      stroke animals.

PMID- 26215753
TI  - The expanding large-spored Metschnikowia clade: Metschnikowia matae sp. nov., a
      yeast species with two varieties from the Brazilian Atlantic Forest.
AB  - Fifty-two yeast isolates from flowers and associated nitidulid beetles of the
      Brazilian Atlantic Forest (Mata Atlantica) region were found to represent a new
      species in the large-spored Metschnikowia clade. The species is heterothallic,
      haploid, and allogamous, and produces asci with two aciculate ascospores that can
      reach 80 MUm in length, as is typical in the clade. Analysis of sequences of the
      ribosomal RNA gene cluster indicates that the new species is closely related to
      Metschnikowia lochheadii, which ranges across Central America to northern Brazil,
      occurs as an adventive species in Hawaii, but is rarely found in central Brazil.
      The species is not readily distinguishable from relatives based on morphology or
      growth responses, but is well delineated from M. lochheadii on reproductive
      isolation. Based on an intron splice site PCR screen, we selected 26 isolates for
      further study. The sequence of the region that includes the complete internal
      transcribed spacer/5.8S rRNA gene segment as well as the D1/D2 domains of the
      large subunit rRNA gene contained three polymorphic segments and 14 haplotypes
      were identified. Of these, a single divergent isolate from the southernmost of
      four sampled localities exhibited diminished mating success when crossed with
      others. We describe two varieties, Metschnikowia matae var. matae sp. nov. var.
      nov. (type UFMG-CM-Y395(T), CBS 13986(T), NRRL Y-63736(T); allotype UFMG-CM
      Y391(A), CBS 13987(A), NRRL Y-63735(A)) and Metschnikowia matae var. maris sp.
      nov. var. nov. (type UFMG-CM-Y397(T), CBS 13985(T), NRRL Y-63737(T)). We also
      report on the discovery of the h (+) mating type of Candida ipomoeae and transfer
      of the species to Metschnikowia ipomoeae comb. nov. (allotype UWOPS 12-660.1(A),
      CBS 13988(A), NRRL Y-63738(A)).

PMID- 26215754
TI  - Can biliary endoscopy play a role in liver disease associated to cystic fibrosis?

PMID- 26215755
TI  - Children with cerebral palsy do not achieve healthy physical activity levels.
AB  - AIM: This study compared daily activity energy expenditure (AEE) in children with
      cerebral palsy with a control group and investigated whether the children
      achieved healthy levels of physical activity. METHODS: We enrolled eight children
      with bilateral cerebral palsy, from eight to 10 years of age, and a group of
      controls matched for age and gender. For three days, physical activity was
      simultaneously measured by accelerometers and self-reports using a diary. The
      daily AEE results were compared between groups and methods. The number of
      children that achieved healthy physical activity levels in each group was
      explored. RESULTS: Children with cerebral palsy had significantly lower daily
      AEE, as measured by accelerometers, than the controls, and they did not achieve
      the healthy moderate to heavy physical activity level defined in the Nordic
      Nutrition Recommendations. Self-reports using the diaries resulted in an
      overestimation of physical activity compared with the ankle accelerometer
      measurements in both groups. CONCLUSION: Our investigation of physical activity
      in children with cerebral palsy and controls using accelerometers and a diary
      found low levels of daily AEE and physical activity, and these results were most
      prominent in the group with cerebral palsy. The diaries overestimated physical
      activity in both groups.

PMID- 26215756
TI  - Shifting anaerobic to aerobic metabolism stimulates apoptosis through modulation
      of redox balance: potential intervention in the pathogenesis of postoperative
      adhesions.
AB  - OBJECTIVE: To compare the effect of shifting anaerobic to aerobic metabolism on
      key regulators of oxidative stress, including extracellular superoxide dismutase
      (SOD3), inducible nitric oxide synthase (iNOS), and its product, nitric oxide
      (NO), as well as mitochondrial potential (Deltapsim) and apoptosis in fibroblasts
      established from normal peritoneum and adhesion tissues. DESIGN: Prospective,
      experimental study. SETTING: University medical center. PATIENT(S): Fibroblasts
      established from normal peritoneum and adhesion tissues from the same patients.
      INTERVENTION(S): Treatment with dichloroacetate (0, 20, 40, and 80 MUg/mL, 24
      hours). MAIN OUTCOME MEASURE(S): The expression of SOD3, iNOS, and NO levels were
      measured utilizing real-time reverse transcription-polymerase chain reaction and
      Greiss assay. The Deltapsim was evaluated by the JC-1 Mitochondrial Membrane
      Potential Assay. Apoptosis was determined by caspase-3 activity and TUNEL assays.
      Data were analyzed using SPSS 19.0. Mixed model repeated-measures analysis of
      variance was used with a Bonferroni correction. Significant interactions were
      analyzed with independent sample t tests. RESULT(S): Dichloroacetate increased
      apoptosis, SOD3 messenger RNA, iNOS messenger RNA, and NO levels in fibroblasts
      from peritoneum and adhesions. There was enhanced Deltapsim adhesion as compared
      with normal peritoneal fibroblasts. Creating oxidative stress by exposure by
      hypoxia markedly increased Deltapsim in fibroblasts from normal peritoneum to
      levels observed in adhesions; dichloroacetate protected against the effects of
      hypoxia. CONCLUSION(S): Anaerobic metabolism and oxidative stress are associated
      with the development of the adhesion phenotype, which manifests decreased
      apoptosis. Dichloroacetate induces adhesion fibroblasts to undergo apoptosis via
      modulation of redox homeostasis. These findings may provide targets for
      therapeutic treatment for reduction of profibrotic disorders, including
      postoperative adhesions.

PMID- 26215757
TI  - Effect of paternal age on reproductive outcomes in oocyte donation model: a
      systematic review.
AB  - OBJECTIVE: To perform a meta-analysis of the literature examining the influence
      of paternal age on oocyte donation outcomes. DESIGN: Systematic review of the
      literature with no language or time restrictions. SETTING: Not applicable.
      PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy and
      live-birth rates. RESULT(S): By independent screening of titles and abstracts,
      two investigators selected original studies examining the influence of paternal
      age on oocyte donation outcomes. Twelve articles were included, encompassing a
      total of 12,538 oocyte-donation cases. No statistically significant correlation
      was found by most studies between advanced paternal age and the rate of
      fertilization, cleavage embryo development, implantation, pregnancy, miscarriage,
      or live birth. A statistically significant decrease in blastocyst embryo
      formation was suggested in two articles. Except for volume and possibly motility,
      other sperm characteristics such as concentration and morphology did not alter
      with age. However, the overall quality of the evidence was rated as very low
      according to Grading of Recommendations Assessment, Development, and Evaluation
      criteria. CONCLUSION(S): The available evidence suggests that advancing paternal
      age is not associated with adverse oocyte donation outcomes, including pregnancy
      and live-birth rates. However, the suboptimal quality of the available evidence
      necessitates high-quality, well-adjusted prospective trials that are also aimed
      at evaluating additional outcomes such as congenital anomalies and various
      specific long-term disorders.

PMID- 26215758
TI  - Dental sealant knowledge, opinion, values and practice of Spanish dental
      hygienists.
AB  - OBJECTIVES: Dental sealants have proved to be an effective approach to prevent
      pit and fissure caries. This study examines the knowledge, opinion, values and
      practice (KOVP) of dental hygienists concerning sealant use in the southwest
      region of Andalusia, Spain. METHODS: Spanish dental hygienists (n = 400)
      volunteered to complete a 31-item, self-administered, pretested questionnaire to
      assess their knowledge, opinion, values and practice regarding pit and fissure
      sealants. Wilcoxon matched-pairs signed ranks test, the Friedman nonparametric
      repeated-measures anova and Spearman's correlation were used to analyse the data.
      RESULTS: The mean scores for knowledge, opinion, values and practice were 3.57 +/
      0.41; 2.17 +/- 0.42; 2.58 +/- 0.77 and 3.56 +/- 0.46, respectively. Knowledge
      differed by years of experience (P < 0.01) and place of work (P < 0.01); opinion
      differed by years of experience (P = 0.03) and sector (P < 0.01). Similarly,
      practice about sealants differed by years of experience (P < 0.01). Conversely,
      values around sealant placement did not statistically differ by sex, years of
      experience, practice sector or place of work. Statistically, significant
      correlations were found between knowledge, opinion and value, while it was found
      no significant correlation between practice and the other variables (P > 0.05).
      CONCLUSIONS: Most dental hygienists have sufficient knowledge about pit and
      fissure sealants. They also acknowledge the importance of use of dental sealants
      and have positive opinion/attitude about using sealants. Practice of dental
      sealants in clinics was found adequate. However, they were not following the
      specific guidelines and standardized procedures.

PMID- 26215759
TI  - Localization of Bovine Papillomavirus Nucleic Acid in Equine Sarcoids.
AB  - Bovine papillomaviruses (BPV1/BPV2) have long been associated with equine
      sarcoids; deciphering their contribution has been difficult due to their
      ubiquitous presence on skin and in the environment, as well as the lack of decent
      techniques to interrogate their role in pathogenesis. We have developed and
      characterized an in situ hybridization (ISH) assay that uses a pool of probes
      complementary to portions of the E5, E6, and E7 genes. This assay is highly
      sensitive for direct visualization of viral transcript and nucleic acid in
      routinely processed histopathologic samples. We demonstrate here the
      visualization of BPV nucleic acid in 18 of 18 equine sarcoids, whereas no
      detectable viral DNA was present in 15 of 15 nonsarcoid controls by this
      technique. In nearly 90% (16/18) of the sarcoids, 50% or more of the fibroblastic
      cell nuclei distributed throughout the neoplasm had detectable hybridization. In
      the remaining 2 cases, fewer than half of the fibroblastic cells contained
      detectable hybridization, but viral nucleic acid was also detected in epithelial
      cells of the sebaceous glands, hair follicles and epidermis. A sensitive ISH
      assay is an indispensable addition to the molecular methods used to detect viral
      nucleic acid in tissue. We have used this technique to determine the specific
      cellular localization and distribution of BPV in a subset of equine sarcoids. 

PMID- 26215760
TI  - Multisystemic Listeriosis in a Common Brushtail Possum (Trichosurus vulpecula)
      and Two Common Ringtail Possums (Pseudocheirus peregrinus).
AB  - A single free-ranging common brushtail possum (Trichosurus vulpecula) and 2
      captive sibling common ringtail possums (Pseudocheirus peregrinus)from a
      zoological facility in Sydney, Australia, were diagnosed with multisystemic
      listeriosis. The brushtail was found dead in an animal enclosure while the
      ringtails presented with signs of cardiovascular collapse and died shortly
      thereafter. All 3 animals were culture positive forListeria monocytogenesand
      demonstrated focal suppurative lesions within the brainstem in addition to
      fulminant disease in other areas of the thorax and/or abdomen. Listeriosis in
      phalangeriformes species has rarely been reported, and brainstem lesions have not
      previously been described. It is speculated that access to the brainstem by the
      organism may have occurred hematogenously or via retrograde migration along
      cranial nerves. Sources of infection and the possibility of transmission between
      animals are also discussed. 

PMID- 26215761
TI  - Cross Lineage Rearrangement in Feline Enteropathy-Associated T-cell Lymphoma.
AB  - Feline enteropathy-associated T-cell lymphoma (EATL) type II is characterized by
      infiltration of the small intestinal mucosa with small T-cells with variable
      epitheliotropism and is often difficult to differentiate from inflammation.
      Polymerase chain reaction (PCR) to assess antigen receptor rearrangements (PARR)
      amplifies the T- (T-cell receptor gamma, TCRG) or B-cell (immunoglobulin heavy
      chain, IGH) antigen receptor genes and is used to differentiate EATL from
      inflammation. However, PARR does not determine lymphocyte phenotype, and clonal
      rearrangement of either or both the TCRG or IGH genes may be detected in
      neoplastic T-cells. The purpose of this study was to determine the incidence of
      cross lineage rearrangement in feline EATL type II. Using a diagnostic algorithm
      combining histology, immunohistochemistry, and PARR testing, 8 of 92 cases
      diagnosed as EATL type II at Michigan State University between January 2013 and
      June 2014 showed cross lineage rearrangement (8.7%). PARR for the IGH gene
      facilitates the diagnosis of cases histologically highly suggestive of EATL type
      II in which polyclonal rearrangement of the TCRG gene is detected. 

PMID- 26215762
TI  - Knowledge and training needs of nurses and physicians on unsuitable drugs for
      patients with dysphagia or feeding tubes.

PMID- 26215763
TI  - A survey of state-of-the-art surface chemistries to minimize fouling from human
      and animal biofluids.
AB  - Upon contact with bodily fluids, synthetic materials spontaneously acquire a
      layer of various species (most notably proteins) on their surface. The concern
      with respect to biomedical equipment, implants or devices resides in the
      possibility for biological processes with potentially harmful effects to ensue.
      In biosensor technology, the issue with this natural fouling phenomenon is that
      of non-specific adsorption to sensing platforms, which generates an often
      overwhelming interference signal that prevents the detection, not to mention the
      quantification, of target analytes present at considerably lower concentration.
      To alleviate this ubiquitous, recurrent problem - this genuine biotechnological
      plague - considerable research efforts have been devoted over the last few
      decades to engineer antifouling coatings. Extensive literature now exists that
      describes stealth organic adlayers capable of reducing fouling surface coverage
      Gamma down to a few ng cm(-2)- however from biotechnologically irrelevant
      buffered solutions free or nearly depleted of any potentially interfering
      species. Regrettably indeed, few coatings are known to display/retain such level
      of performance when exposed to otherwise more complex, real-life biosamples (even
      diluted). Herein, we comprehensively review the state-of-the-art surface
      chemistries developed to date (January 2015) to minimize fouling from 8 such
      uncomparatively more challenging biological media (blood plasma, blood serum,
      cell lysate, cerebrospinal fluid, egg, milk, saliva, and urine) - whether of
      human or animal origin. Literature search for another 25 biological milieux
      generated no (exploitable) hit. Also discussed in this Review are the
      identification of the species responsible for fouling, and the dependence of
      antifouling properties on biosample source variability. 

PMID- 26215764
TI  - Amino acid efflux by asexual blood-stage Plasmodium falciparum and its utility in
      interrogating the kinetics of hemoglobin endocytosis and catabolism in vivo.
AB  - The endocytosis and catabolism of large quantities of host cell hemoglobin is a
      hallmark of the intraerythrocytic asexual stage of the human malaria parasite
      Plasmodium falciparum. It is known that the parasite's production of amino acids
      from hemoglobin far exceeds its metabolic needs. Here, we show that P. falciparum
      effluxes large quantities of certain non-polar (Ala, Leu, Val, Pro, Phe, Gly) and
      polar (Ser, Thr, His) amino acids to the external medium. That these amino acids
      originate from hemoglobin catabolism is indicated by the strong correlation
      between individual amino acid efflux rates and their abundances in hemoglobin,
      and the ability of the food vacuole falcipain inhibitor E-64d to greatly suppress
      efflux rates. We then developed a rapid, sensitive and precise method for
      quantifying flux through the hemoglobin endocytic-catabolic pathway that is based
      on leucine efflux. Optimization of the method involved the generation of a novel
      amino acid-restricted RPMI formulation as well as the validation of D-norvaline
      as an internal standard. The utility of this method was demonstrated by
      characterizing the effects of the phosphatidylinositol-3-kinase inhibitors
      wortmannin and dihydroartemisinin on the kinetics of Leu efflux. Both compounds
      rapidly inhibited Leu efflux, which is consistent with a role for
      phosphtidylinositol-3-phosphate production in the delivery of hemoglobin to the
      food vacuole; however, wortmannin inhibition was transient, which was likely due
      to the instability of this compound in culture medium. The simplicity,
      convenience and non-invasive nature of the Leu efflux assay described here makes
      it ideal for characterizing the in vivo kinetics of hemoglobin endocytosis and
      catabolism, for inhibitor target validation studies, and for medium-throughput
      screens to identify novel inhibitors of cytostomal endocytosis. 

PMID- 26215766
TI  - Dynamic systems and the role of evaluation: The case of the Green Communities
      project.
AB  - The crucial role evaluation can play in the co-development of project design and
      its implementation will be addressed through the analysis of a case study, the
      Green Communities (GC) project, funded by the Italian Ministry of Environment
      within the EU Interregional Operational Program (2007-2013) "Renewable Energy and
      Energy Efficiency". The project's broader goals included an attempt to trigger a
      change in Italian local development strategies, especially for mountain and
      inland areas, which would be tailored to the real needs of communities, and based
      on a sustainable exploitation and management of the territorial assets. The goal
      was not achieved, and this paper addresses the issues of how GC could have been
      more effective in fostering a vision of change, and which design adaptations and
      evaluation procedures would have allowed the project to better cope with the
      unexpected consequences and resistances it encountered. The conclusions drawn are
      that projects should be conceived, designed and carried out as dynamic systems,
      inclusive of a dynamic and engaged evaluation enabling the generation of
      feedbacks loops, iteratively interpreting the narratives and dynamics unfolding
      within the project, and actively monitoring the potential of various
      relationships among project participants for generating positive social change. 

PMID- 26215765
TI  - Visit-to-Visit Variability of Blood Pressure and Coronary Heart Disease, Stroke,
      Heart Failure, and Mortality: A Cohort Study.
AB  - BACKGROUND: Variability of blood pressure (BP) across outpatient visits is
      frequently dismissed as random fluctuation around a patient's underlying BP.
      OBJECTIVE: To examine the association of visit-to-visit variability (VVV) of
      systolic BP (SBP) and diastolic BP with cardiovascular disease (CVD) and
      mortality outcomes. DESIGN: Prospective cohort study. SETTING: Post hoc analysis
      of ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
      Trial). PARTICIPANTS: 25 814 ALLHAT participants. MEASUREMENTS: The VVV of SBP
      was defined as the SD across SBP measurements obtained at 7 visits conducted from
      6 to 28 months after ALLHAT enrollment. Participants without CVD events during
      the first 28 months of follow-up were followed from the 28-month visit through
      the end of active ALLHAT follow-up. Outcomes included fatal coronary heart
      disease (CHD) or nonfatal myocardial infarction, all-cause mortality, stroke, and
      heart failure. RESULTS: During follow-up, 1194 fatal CHD or nonfatal MI events,
      1948 deaths, 606 strokes, and 921 heart failure events occurred. After
      multivariable adjustment, including for mean SBP, the hazard ratio comparing
      participants in the highest versus lowest quintile of SD of SBP (>=14.4 mm Hg vs.
      <6.5 mm Hg) was 1.30 (95% CI, 1.06 to 1.59) for fatal CHD or nonfatal MI, 1.58
      (CI, 1.32 to 1.90) for all-cause mortality, 1.46 (CI, 1.06 to 2.01) for stroke,
      and 1.25 (CI, 0.97 to 1.61) for heart failure. Higher VVV of diastolic BP was
      also associated with CVD events and mortality. LIMITATION: Long-term outcomes
      were not available. CONCLUSION: Higher VVV of SBP is associated with an increased
      risk for CVD and mortality. Future studies should examine whether reducing VVV of
      BP lowers this risk. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 26215767
TI  - Radiation Reduction Capabilities of a Next-Generation Pediatric Imaging Platform.
AB  - The aims of this study were to quantify patient radiation exposure for a single
      interventional procedure during transition from an adult catheterization
      laboratory to a next-generation imaging system with pediatric settings, and to
      compare this radiation data to published benchmarks. Radiation exposure occurs
      with any X-ray-directed pediatric catheterization. Technologies and imaging
      techniques that limit dose while preserving image quality benefit patient care.
      Patient radiation dose metrics, air kerma, and dose-area product (DAP) were
      retrospectively obtained for patients <20 kg who underwent patent ductus
      arteriosus (PDA) closure on a standard imaging system (Group 1, n = 11) and a
      next-generation pediatric imaging system (Group 2, n = 10) with air-gap
      technique. Group 2 radiation dose metrics were then compared to published
      benchmarks. Patient demographics, procedural technique, PDA dimensions, closure
      devices, and fluoroscopy time were similar for the two groups. Air kerma and DAP
      decreased by 65-70% in Group 2 (p values <0.001). The average number of
      angiograms approached statistical significance (p value = 0.06); therefore,
      analysis of covariance (ANCOVA) was conducted that confirmed significantly lower
      dose measures in Group 2. This degree of dose reduction was similar when Group 2
      data (Kerma 28 mGy, DAP 199 uGy m(2)) was compared to published benchmarks for
      PDA closure (Kerma 76 mGy, DAP 500 uGy m(2)). This is the first clinical study
      documenting the radiation reduction capabilities of a next-generation pediatric
      imaging platform. The true benefit of this dose reduction will be seen in
      patients requiring complex and often recurrent catheterizations.

PMID- 26215768
TI  - Effect of Tadalafil on Myocardial and Endothelial Function and Exercise
      Performance After Modified Fontan Operation.
AB  - Better postoperative management of patients who have undergone single ventricle
      (SV) Fontan procedure could potentially reduce long-term complications and
      improve the quality of life for patients. The present study determined the effect
      of tadalafil on myocardial and endothelial function and exercise performance
      after modified Fontan operation. Patients who had undergone SV modified Fontan
      operation were enrolled in this clinical trial. The demographic characteristics
      of the patients were recorded. Before administration of tadalafil and after the
      trial, ventricular function (MPI, EF, FS, E/A, VTI), exercise performance, and
      endothelial function were evaluated for sonographic and biochemical markers (FMD,
      IMT, ICAM, VCAM, NO) using echocardiography, exercise testing, vascular
      ultrasonography, and biochemical measurements, respectively. A single dose of
      tadalafil of 1 mg/kg was administered daily for 6 weeks, and the functional class
      of the patients before and after tadalafil was determined. A total of 15 patients
      completed this clinical trial. Tadalafil was shown to have a significant effect
      on myocardial function, exercise performance, and improvement in NYHA functional
      class (p < 0.05) of study population. It had no significant effect on the
      biochemical variables and endothelial function except for IMT (p > 0.05), which
      decreased significantly after tadalafil administration (p < 0.05). The findings
      indicate that tadalafil is a safe, well-tolerated agent for the use after
      modified Fontan operation to improve myocardial function and exercise performance
      and possibly reduce long-term morbidity and mortality of patients. More
      conclusive results could be obtained from further study with a larger sample size
      and long-term follow-up. 

PMID- 26215769
TI  - Optical nanoscopy of transient states in condensed matter.
AB  - Recently, the fundamental and nanoscale understanding of complex phenomena in
      materials research and the life sciences, witnessed considerable progress.
      However, elucidating the underlying mechanisms, governed by entangled degrees of
      freedom such as lattice, spin, orbit, and charge for solids or conformation,
      electric potentials, and ligands for proteins, has remained challenging.
      Techniques that allow for distinguishing between different contributions to these
      processes are hence urgently required. In this paper we demonstrate the
      application of scattering-type scanning near-field optical microscopy (s-SNOM) as
      a novel type of nano-probe for tracking transient states of matter. We introduce
      a sideband-demodulation technique that allows for probing exclusively the stimuli
      induced change of near-field optical properties. We exemplify this development by
      inspecting the decay of an electron-hole plasma generated in SiGe thin films
      through near-infrared laser pulses. Our approach can universally be applied to
      optically track ultrafast/-slow processes over the whole spectral range from UV
      to THz frequencies. 

PMID- 26215770
TI  - A sham-controlled trial of acupressure on the quality of sleep and life in
      haemodialysis patients.
AB  - BACKGROUND: Sleep disorder in haemodialysis patients can lead to disturbance in
      their psychosocial function and interpersonal relations, and reduced quality of
      life. The aim of the present study was to investigate the effect of acupressure
      on the quality of sleep of haemodialysis patients. METHODS: In a randomised
      controlled trial, 108 haemodialysis patients were randomly divided into three
      groups: true acupressure, placebo acupressure, and no treatment. The two
      acupressure groups received treatment three times a week for 4 weeks during
      dialysis. Routine care only was provided for the no treatment group. The main
      study outcome was sleep quality. RESULTS: The total Pittsburgh Sleep Quality
      Index score decreased significantly from 11.9+/-3.13 to 6.2+/-1.93 in the true
      acupressure group, from 11.3+/-3.69 to 10.6+/-3.82 in the sham acupressure group,
      and from 10.9+/-4.10 to 10.7+/-3.94 in the no treatment group. There was a
      significant difference between groups (p<0.001). CONCLUSIONS: Acupressure seems
      to have a positive effect on the sleep quality in haemodialysis patients.
      CLINICAL TRIAL REGISTRATION: IRCT201106145864N2.

PMID- 26215771
TI  - Efficacy of tenofovir disoproxil fumarate to prevent vertical transmission in
      mothers with lamivudine-resistant HBV.
AB  - BACKGROUND: In China, women with chronic HBV infection and who are of
      childbearing age receive lamivudine at an early age. Thus, viral resistance
      becomes a challenge for intervention to prevent mother-to-infant transmission. We
      prospectively assessed the efficacy of tenofovir in pregnant women with
      lamivudine-resistant HBV. METHODS: Chronic HBV-infected mothers resistant to
      lamivudine were enrolled. Tenofovir was administrated at gestation weeks 24 or
      28. Virological and biochemical parameters were assessed. All infants received
      combined immunoprophylaxis and were followed for 1 year. RESULTS: Of the 48
      mothers enrolled, 21 started tenofovir therapy at gestation week 24 and 27
      started at week 28. Tenofovir resulted in an HBV DNA decline of 5.23 +/- 1.68
      log10 IU/ml at delivery. The group starting therapy at week 24 exhibited a more
      rapid viral inhibition (P<0.001) and more significant HBV DNA load decline (5.89
      +/- 1.66 versus 4.72 +/- 1.55; P=0.019) than the group starting at week 28. At
      delivery, all mothers had a viral titre <10(6) IU/ml, 76.2% from the week 24
      starting group displayed virus <10(4) IU/ml, and 52.4% showed undetectable virus
      at delivery, much higher than the week 28 starting group (29.6%), although there
      was no statistically significant difference in viral levels at delivery between
      the two groups. Congenital abnormalities and neonatal growth were comparable to
      the normal population. No case of perinatal transmission was diagnosed.
      CONCLUSIONS: This investigation clarifies the efficacy of tenofovir for reducing
      vertical transmission of HBV in mothers with lamivudine-resistant HBV and
      demonstrates that tenofovir is well-tolerated in the second and third trimesters.

PMID- 26215772
TI  - Cartilaginous tibial eminence fractures in children: which recommendations for
      management of this new entity?
AB  - PURPOSE: Cartilaginous tibial eminence fracture (CTEF) is a new pattern of ACL
      rupture in children under the age of nine. MRI signs have been recently reported,
      but no series gave information about outcomes. It was hypothesized that primary
      treatment gave better results than delayed management due to frequent
      misdiagnosis. METHOD: This retrospective study focused on 15 patients, managed
      acutely (n = 7) or delayed (n = 8). The patients' median age at the time of
      initial injury was 6.5 years (range 5-9). Lysholm, IKDC 2000 subjective scores,
      and the measurement of the residual laxity by a side-to-side difference with a KT
      1000 junior arthrometer were used at the time of revision. RESULTS: After a mean
      follow-up of 9.8 years (range 1-18.5), the mean Lysholm and IKDC subjective
      scores were, respectively, 97.7 +/- 2.6 and 97 +/- 3.4. The median residual
      laxity was 2 mm (range 0-4). Non-operative treatment lead to 2 failures:
      intermeniscal ligament entrapment and combined avulsion fracture at the femoral
      site. Suture fixation of the avulsed fragment allows regularly good results when
      performed acutely or even 4 years after the injury. The hypothesis that primary
      treatment gives better result than delayed treatment tends to be wrong as 2
      failures were reported in each group. An ACL reconstruction was performed in 3
      out of the 4 treatment failures. Progressive resorption of the avulsed fragment
      was noticed in 3 of the 4 failures suggesting an associated ACL resorption.
      CONCLUSION: CTEF has a good prognosis even after misdiagnosis and treatment at
      the time of non-union; this could be due to low-energy mechanism of injury and
      low rate of associated lesion. Orthopaedic treatment for acute minimally
      displaced fractures is only indicated under strict MRI control, and suture
      fixation is the recommended strategy in other situations. Conservative management
      of non-union could expose to ACL involution and cannot be recommended. LEVEL OF
      EVIDENCE: Retrospective case series, Level IV.

PMID- 26215773
TI  - After early release of tourniquet in total knee arthroplasty, should it be
      reinflated or kept deflated? A randomized trial.
AB  - PURPOSE: This study was undertaken to determine the efficacy of reinflation of
      the tourniquet after its early release in TKA compared to early release alone, in
      terms of surgical field visualization and operative time. We also questioned
      whether tourniquet reinflation after its early release is safe, with respect to
      post-operative blood loss, post-operative pain and other tourniquet-related
      complications. METHODS: Two hundred and six patients undergoing TKA were randomly
      allocated to either the early release (deflation) group (n = 105) or reinflation
      after early release (reinflation) group (n = 101). Efficacy was measured in terms
      of surgical field visualization, specifically the number of wound clearances, and
      operative time. Safety outcomes were drained volume, decline in haemoglobin on
      post-operative days 2 and 5, the frequency of transfusion, knee and thigh pain
      visual analog scale, local wound complications, tourniquet site complications and
      other complications, including infection, deep vein thrombosis and pulmonary
      embolism. RESULTS: Surgical field visualization was better in the reinflation
      group; however, the operative time did not differ between the two groups. There
      were no differences between the two groups in post-operative blood loss, decline
      in haemoglobin on days 2 and 5, transfusion rate, pain level, local complications
      and other complications. CONCLUSION: Reinflation of tourniquet is a safe
      alternative to its early release after deflation in that it improves surgical
      field visualization during TKA. LEVEL OF EVIDENCE: Therapeutic study, Level I.

PMID- 26215774
TI  - Moderate clinical improvement after revision arthroplasty of the severely stiff
      knee.
AB  - PURPOSE: Revision of the severe stiff total knee arthroplasty (TKA) is
      challenging, and clinical outcome is inferior to other indications for revision.
      The purpose of the present study was to determine clinical outcome of TKA
      revision in patients with severe stiffness (range of motion (ROM) <= 70 degrees )
      and evaluate a possible influence of accompanying findings, such as component
      malposition, aseptic loosening or instability. METHODS: A prospective cohort of
      40 patients with a preoperative ROM <= 70 degrees  and a minimum of 2-year follow
      up after total system revision (Genesis or Legion stemmed condylar implant) was
      evaluated. ROM, Knee Society Scoring System (KSS) and visual analogue scale (VAS)
      pain scores were obtained preoperatively and at 2 years. Patient satisfaction and
      complication rate were assessed. Component malposition was most frequently
      reported as accompanying finding (n = 27). Comparisons between pre- and
      postoperative outcome (p < 0.05) and between different subgroups (component
      malposition, aseptic loosening, and instability) based on accompanying findings
      were made (no statistical comparison). RESULTS: ROM, KSS and VAS pain scores
      improved significantly (p < 0.001): median ROM at two years 85 degrees  (range 10
      125) and median gain 25 degrees  (range -10 to +85). Median VAS satisfaction was
      53.5 points (range 15-98). Seventeen patients reported at least one complication,
      including one re-revision. Six patients underwent manipulation under anaesthesia,
      and five were referred to the pain clinic. No clear differences between subgroups
      were observed. CONCLUSIONS: TKA revision in patients with severe stiffness
      resulted in a moderate but significant improved clinical outcome after 2 years.
      Accompanying abnormalities such as component malposition, aseptic loosening or
      instability did not influence clinical outcome. Realistic patient counselling on
      the moderate outcome and possible remaining limitations in daily life might help
      to improve patient satisfaction. LEVEL OF EVIDENCE: Therapeutic studies-case
      series with no comparison group, Level IV.

PMID- 26215775
TI  - Primary patellar dislocations without surgical stabilization or recurrence: how
      well are these patients really doing?
AB  - PURPOSE: While a significant research has gone into identifying patients at
      highest risk of recurrence following primary patellar dislocation, there has been
      little work exploring the outcomes of patients who do not have a recurrent
      patellar dislocation. We hypothesize that patients without recurrent dislocation
      episodes will exhibit significantly higher KOOSs than those who suffer recurrent
      dislocations, but lower scores than published age-matched normative data.
      METHODS: A retrospective review of patients with nonoperatively treated primary
      lateral patellar dislocations was carried out, and patients were contacted at a
      mean of 3.4 years (range 1.3-5.5 years) post-injury. Information regarding
      subsequent treatment and recurrent dislocations along with patient-reported
      outcome scores and activity level was collected. RESULTS: One hundred and eleven
      patients (29.8 %) of 373 eligible patients agreed to study participation, seven
      of whom were excluded because they underwent subsequent patellar stabilization
      surgery on the index knee. Seventy-six patients (73.1 %) reported no further
      dislocation events, and the mean KOOS subscales at follow-up were: symptoms-80.2
      +/- 18.8, pain-81.8 +/- 16.2, ADL-88.7 +/- 15.9, sport/recreation-72.1 +/- 24.4,
      and QOL-63.9 +/- 23.8 at a mean follow-up of 3.3 years (range 1.3-5.5 years). No
      significant differences in any of the KOOS subscales were noted between these
      patients and the group that reported recurrent patellar dislocations. Only 26.4 %
      of the patients without further dislocations reported they were able to return to
      desired sport activities without limitations following their dislocation.
      CONCLUSION: Patients who do not report recurrent patellar dislocations following
      nonoperative treatment of primary patellar dislocations are in many cases limited
      by this injury 3 years following the initial dislocation event. LEVEL OF
      EVIDENCE: Retrospective cohort study, Level III.

PMID- 26215777
TI  - Alteplase is safe to use within existing treatment guidelines, says independent
      review.

PMID- 26215776
TI  - Simultaneous bilateral multiligamentous knee injuries are associated with more
      severe multisystem trauma compared to unilateral injuries.
AB  - PURPOSE: To compare the knee ligamentous injury patterns and associated
      multisystem trauma in patients who have sustained simultaneous bilateral knee
      multiligamentous injuries (MLI) to patients with unilateral MLIs. METHODS:
      Patients with simultaneous bilateral and unilateral knee MLIs after motor vehicle
      accidents were identified from 2007 to 2014 at a single institution. Chart and
      radiographic reviews were performed to identify patient demographics, extremity
      fractures and associated head, thoracic, abdominal and spine injuries. The MLIs
      were characterized by ligamentous injury pattern and associated neurovascular
      deficits. Injury Severity Score (ISS) and New ISS (NISS) were calculated.
      RESULTS: Seven bilateral MLIs and 32 unilateral MLIs were identified. Between the
      cohorts, there were no significant differences in ligamentous injury pattern or
      associated neurovascular injuries. For the bilateral MLI cohorts, 71.4 % of
      patients sustained chest trauma, 57.1 % abdominal trauma, 57.1 % at least a
      single-level spine injury and 28.6 % head trauma. The ISS was 33.4 +/- 23.4 with
      patients spending an average of 12.4 days in the intensive care unit. Other than
      the number of days in the ICU, these values were all significantly higher than
      those of the unilateral knee MLI cohort. Additionally, there was a significantly
      higher post-operative complication rate in the bilateral MLI cohort (71.4 vs. 6.3
      %, P < 0.0001). CONCLUSION: Compared to unilateral MLIs with similar mechanisms,
      patients with traumatic simultaneous bilateral knee multiligamentous knee
      injuries are at high risk of concomitant head, chest and abdominal injuries.
      Although the ligament injury profile is similar, the post-operative complication
      rate is higher for simultaneous bilateral injuries. LEVEL OF EVIDENCE: Case
      control study, Level III.

PMID- 26215778
TI  - Postoperative Atrial Fibrillation Is Associated With High On-Aspirin Platelet
      Reactivity.
AB  - BACKGROUND: Atrial fibrillation (AF) contributes to a prothrombotic state through
      platelet activation. It is unclear whether increased platelet aggregability in
      patients with AF is caused by the underlying cardiovascular condition rather than
      the arrhythmia per se. We investigated the effect of postoperative atrial
      fibrillation (POAF) on platelet reactivity after coronary artery bypass grafting
      (CABG). METHODS: This study is a post hoc analysis from a randomized controlled
      trial (ClinicalTrials.gov: NCT01159639) based on patients undergoing elective
      primary CABG. Patients were dichotomized according to POAF. Postoperative
      platelet function testing with arachidonic acid as the platelet agonist (ASPI
      test) was used to define high on-aspirin platelet reactivity (HAPR). DeltaASPI
      presented the difference between pre- and postoperative ASPI test values. To
      account for the isolated effect of POAF on platelet reactivity, a propensity
      score analysis was applied. RESULTS: Overall incidence of POAF was 23% (92 of 398
      patients). HAPR was detected in 54% (214 of 398) of patients. HAPR was more
      prevalent among patients with POAF when compared with patients without POAF
      (64.1% versus 50.7%; odds ratio [OR], 1.74; 95% confidence interval [CI], 1.08
      2.82; p = 0.023). The propensity score model produced a subcohort of patients
      that was well balanced for comorbidities. When compared with the matched group
      without POAF, the POAF group maintained its prevalence for HAPR (64.1% versus
      45.7%; OR, 2.13; 95% CI, 1.18-3.85; p = 0.012) and had greater DeltaASPI values
      (15.0 [IQR, 0.0-36.0] vs 8.0 [IQR, -5.5-19.5]; p = 0.030). CONCLUSIONS: The main
      finding of our study indicates there is added platelet activation in patients
      with POAF after CABG before and after controlling for pathologic conditions
      through propensity matching. The present study does not prove a causal
      association between POAF and HAPR.

PMID- 26215779
TI  - Electrophysiologic Results After Thoracoscopic Ablation for Chronic Atrial
      Fibrillation.
AB  - BACKGROUND: Thoracoscopic ablation for lone atrial fibrillation (AF) has evolved
      rapidly in the past decade. We investigated the electrophysiologic results and
      midterm durability of totally thoracoscopic ablation in patients with lone
      persistent AF. METHODS: Seventy-nine consecutive patients with paroxysmal AF (8
      patients, 10.1%), persistent AF (17 patients, 21.5%), and long-standing
      persistent AF (54 patients, 68.3%) were prospectively enrolled. Thoracoscopic
      ablation consisted of a bilateral closed-chest approach to performing pulmonary
      isolation (a box lesion), ganglionated plexus ablation, division of the Marshall
      ligament, and left atrial auricle resection. An electrophysiologic study was
      performed 5 days after the surgical procedure in 61 patients (77%). Freedom from
      AF was assessed with electrocardiograms or Holter monitoring every 3 months, with
      a mean follow-up of 12.1 (maximum, 28) months. RESULTS: No deaths or conversion
      to cardiopulmonary bypass occurred. During electrophysiologic study, 28 residual
      pulmonary vein potentials were observed in 15 patients (19%). Out of a total of
      28 gaps, 20 (71%) were located in the superior and inferior ridges of pulmonary
      veins. Six gaps (21%) were detected in the carina of pulmonary veins. The mitral
      isthmus was ablated in 2 patients (7%). Freedom from AF at 2 years was 92.6 +/-
      3.3%. Freedom from cardiac-related events at 2 years was 74.7 +/- 6.0%. Cox
      regression analysis demonstrated that the predictors of atrial arrhythmias were
      old age, hypertension, and left atrial volume index. CONCLUSIONS: Thoracoscopic
      ablation followed by electrophysiologic confirmation was safe and provided
      excellent midterm durability in patients with AF. However, the incidence of
      residual potentials around the pulmonary veins was not negligible.

PMID- 26215780
TI  - Use of colistin-containing products within the European Union and European
      Economic Area (EU/EEA): development of resistance in animals and possible impact
      on human and animal health.
AB  - Since its introduction in the 1950s, colistin has been used mainly as a topical
      treatment in human medicine owing to its toxicity when given systemically. Sixty
      years later, colistin is being used as a last-resort drug to treat infections
      caused by multidrug-resistant (MDR) Pseudomonas aeruginosa, Acinetobacter
      baumannii and Enterobacteriaceae (e.g., Escherichia coli, Klebsiella pneumoniae),
      for which mortality can be high. In veterinary medicine, colistin has been used
      for decades for the treatment and prevention of infectious diseases. Colistin has
      been administered frequently as a group treatment for animal gastrointestinal
      infections caused by Gram-negative bacteria within intensive husbandry systems.
      Given the ever-growing need to retain the efficacy of antimicrobials used to
      treat MDR infections in humans, the use of colistin in veterinary medicine is
      being re-evaluated. Despite extensive use in veterinary medicine, there is
      limited evidence for the development of resistance to colistin and no evidence
      has been found for the transmission of resistance in bacteria that have been
      spread from animals to humans. Since surveillance for colistin resistance in
      animals is limited and the potential for such transmission exists, there is a
      clear need to reinforce systematic monitoring of bacteria from food-producing
      animals for resistance to colistin (polymyxins). Furthermore, colistin should
      only be used for treatment of clinically affected animals and no longer for
      prophylaxis of diseases, in line with current principles of responsible use of
      antibiotics. 

PMID- 26215781
TI  - Anxiety levels and perceived pain intensity during intravitreal injections.

PMID- 26215782
TI  - Metformin and prostate cancer stem cells: a novel therapeutic target.
AB  - Prostate cancer is the second most frequently diagnosed cancer in the world.
      Localized disease can be effectively treated with radiation therapy or radical
      prostatectomy. However, advanced prostate cancer is more difficult to treat and
      if metastatic, is incurable. There is a need for more effective therapy for
      advanced prostate cancer. One potential target is the cancer stem cell (CSC).
      CSCs have been described in several solid tumors, including prostate cancer, and
      contribute to therapeutic resistance and tumor recurrence. Metformin, a common
      oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti
      neoplastic effects. Specifically, metformin targets CSCs in breast cancer,
      pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the
      mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP
      production. This forces tumor cells to compensate by increasing the rate of
      glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for
      energy production. The glycolytic switch results in an energy crisis in these
      cells. Metformin could be used to exploit this metabolic weakness in CSCs. This
      would increase CSC sensitivity to conventional cancer therapies, circumventing
      treatment resistance and enhancing treatment efficacy. This review will explore
      the characteristics of prostate CSCs, their role in tumor propagation and
      therapeutic resistance and the role of metformin as a potential prostate CSC
      sensitizer to current anticancer therapies. 

PMID- 26215783
TI  - Association of male circumcision with risk of prostate cancer: a meta-analysis.
AB  - BACKGROUND: Although early reports have suggested an association between
      circumcision and prostate cancer (PCa) development, results of subsequent
      epidemiological studies have been conflicting. Here we examine published articles
      that explore this association. METHODS: We searched MEDLINE through PubMed and
      Embase for articles reporting on the association between PCa and circumcision,
      and performed a meta-analysis of qualifying studies. RESULTS: On the basis of
      seven reports of case-control studies published from 1971 to 2014, overall
      findings showed nonsignificant reduced risk (odds ratio (OR) 0.88, P=0.19) of PCa
      in circumcised men compared with uncircumcised men, obtained under heterogeneous
      conditions (I(2)=65%). Heterogeneity and nonsignificance were erased when the
      overall effect was subjected to outlier treatment and three studies omitted (OR
      0.90, P=0.04, I(2)=0%). Furthermore, subgroup analysis showed significantly
      reduced risks in the following subgroups: (i) post-PSA testing publications (OR
      0.88, P=0.01), (ii) population-based studies (OR 0.84, P=0.05), (iii) studies
      that collected data by personal interview (OR 0.83, P=0.03) and (iv) studies in
      black race (OR 0.59, P=0.02). The strengths of these summary effects lie in the
      robustness revealed by sensitivity analysis. CONCLUSIONS: Stability of the
      reduced risks observed in key subgroups suggests that the protective feature of
      circumcision status against PCa is best seen in the context of the post-PSA
      testing and population-based studies as well as in the black race subgroup.

PMID- 26215785
TI  - Radical C-H alkylation of BODIPY dyes using potassium trifluoroborates or boronic
      acids.
AB  - A one-step synthetic procedure for the radical C?H alkylation of BODIPY dyes has
      been developed. This new reaction generates alkyl radicals through the oxidation
      of boronic acids or potassium trifluoroborates and allows the synthesis of mono-,
      di-, tri-, and tetraalkylated fluorophores in a good to excellent yield for a
      broad range of organoboron compounds. Using this protocol, multiple bulky alkyl
      groups can be introduced onto the BODIPY core thus creating solid-state emissive
      BODIPY dyes. 

PMID- 26215784
TI  - Anti-Abeta antibodies incapable of reducing cerebral Abeta oligomers fail to
      attenuate spatial reference memory deficits in J20 mice.
AB  - Compelling genetic evidence links the amyloid precursor protein (APP) to
      Alzheimer's disease (AD). A leading hypothesis proposes that a small amphipathic
      fragment of APP, the amyloid beta-protein (Abeta), self-associates to form
      soluble assemblies loosely referred to as "oligomers" and that these are primary
      mediators of synaptic dysfunction. As such, Abeta, and specifically Abeta
      oligomers, are targets for disease modifying therapies. Currently, the most
      advanced experimental treatment for AD relies on the use of anti-Abeta
      antibodies. In this study, we tested the ability of the monomer-preferring
      antibody, m266 and a novel aggregate-preferring antibody, 1C22, to attenuate
      spatial reference memory impairments in J20 mice. Chronic treatment with m266
      resulted in a ~70-fold increase in Abeta detected in the bloodstream, and a ~50%
      increase in water-soluble brain Abeta--and in both cases Abeta was bound to m266.
      In contrast, 1C22 increased the levels of free Abeta in the bloodstream, and
      bound to amyloid deposits in J20 brain. However, neither 1C22 nor m266 attenuated
      the cognitive deficits evident in 12month old J20 mice. Moreover, both antibodies
      failed to alter the levels of soluble Abeta oligomers in J20 brain. These results
      suggest that Abeta oligomers may mediate the behavioral deficits seen in J20 mice
      and highlight the need for the development of aggregate-preferring antibodies
      that can reach the brain in sufficient levels to neutralize bioactive Abeta
      oligomers. Aside from the lack of positive effect of m266 and 1C22 on cognition,
      a substantial number of deaths occurred in m266- and 1C22-immunized J20 mice.
      These fatalities were specific to anti-Abeta antibodies and to the J20 mouse line
      since treatment of wild type or PDAPP mice with these antibodies did not cause
      any deaths. These and other recent results indicate that J20 mice are
      particularly susceptible to targeting of the APP/Abeta/tau axis. Notwithstanding
      the specificity of fatalities for J20 mice, it is worrying that the murine
      precursor (m266) of a lead experimental therapeutic, Solanezumab, did not engage
      with putatively pathogenic Abeta oligomers.

PMID- 26215786
TI  - Selenocysteine-independent suppression of UGA codons in the archaeon
      Methanococcus maripaludis.
AB  - BACKGROUND: Proteins containing selenocysteine (sec) are found in Bacteria,
      Eukarya, and Archaea. While selenium-dependence of methanogenesis from H(2)+CO(2)
      in the archaeon Methanococcus maripaludis JJ is compensated by induction of a set
      of cysteine-containing homologs, growth on formate is abrogated in the absence of
      sec due to the dependence of formate dehydrogenase (Fdh) on selenium. Despite
      this dependence, formate-dependent growth occurs after prolonged incubation of M.
      maripaludis mutants lacking sec. METHODS: To study this phenomenon, a M.
      maripaludis strain with only one Fdh isoform and an FdhA selenoprotein C
      terminally tagged for affinity enrichment was constructed. Factors required for
      sec synthesis were deleted in this strain and translation of UGA in fdhA was
      analyzed physiologically, enzymatically, immunologically, and via mass
      spectrometry. RESULTS: M. maripaludis JJ mutants lacking sec synthesis grew at
      least five times more slowly than the wild type on formate due to a 20-35-fold
      reduction of Fdh activity. The enzyme in the mutant strains lacked sec but was
      still produced as a full-length protein. Peptide mass spectrometry revealed that
      both cysteine (cys) and tryptophan (trp) were inserted at the UGA encoding sec
      without apparent mutations in tRNA(cys) or tRNA(trp), respectively. CONCLUSIONS:
      We demonstrate that M. maripaludis has the inherent capacity to translate UGA
      with cys and trp; other mechanisms to replace sec with cys in the absence of
      selenium could thereby be ruled out. GENERAL SIGNIFICANCE: This study exemplifies
      how an organism uses the inherent flexibility in its canonical protein synthesis
      machinery to recover some activity of an essential selenium-dependent enzyme in
      the absence of sec.

PMID- 26215787
TI  - Modulation of aldose reductase activity by aldose hemiacetals.
AB  - BACKGROUND: Glucose is considered as one of the main sources of cell damage
      related to aldose reductase (AR) action in hyperglycemic conditions and a
      worldwide effort is posed in searching for specific inhibitors of the enzyme.
      This AR substrate has often been reported as generating non-hyperbolic kinetics,
      mimicking a negative cooperative behavior. This feature was explained by the
      simultaneous action of two enzyme forms acting on the same substrate. METHODS:
      The reduction of different aldoses and other classical AR substrates was studied
      using pure preparations of bovine lens and human recombinant AR. RESULTS: The
      apparent cooperative behavior of AR acting on glucose and other hexoses and
      pentoses, but not on tethroses, glyceraldehyde, 4-hydroxynonenal and 4
      nitrobenzaldehyde, is generated by a partial nonclassical competitive inhibition
      exerted by the aldose hemiacetal on the reduction of the free aldehyde. A kinetic
      model is proposed and kinetic parameters are determined for the reduction of l
      idose. CONCLUSIONS: Due to the unavoidable presence of the hemiacetal, glucose
      reduction by AR occurs under different conditions with respect to other relevant
      AR-substrates, such as alkanals and alkenals, coming from membrane lipid
      peroxidation. This may have implications in searching for AR inhibitors. The
      emerging kinetic parameters for the aldoses free aldehyde indicate the remarkable
      ability of the enzyme to interact and reduce highly hydrophilic and bulky
      substrates. GENERAL SIGNIFICANCE: The discovery of aldose reductase modulation by
      hemiacetals offers a new perspective in searching for aldose reductase inhibitors
      to be developed as drugs counteracting the onset of diabetic complications.

PMID- 26215788
TI  - Linear Discriminant Analysis Identifies Mitochondrially Localized Proteins in
      Neurospora crassa.
AB  - Besides their role as powerhouses, mitochondria play a pivotal role in the
      spatial organization of numerous enzymatic functions. They are connected to the
      ER, and many pathways are organized through the mitochondrial membranes. Thus,
      the precise definition of mitochondrial proteomes remains a challenging task.
      Here, we have established a proteomic strategy to accurately determine the
      mitochondrial localization of proteins from the fungal model organism Neurospora
      crassa. This strategy relies on both highly pure mitochondria as well as the
      quantitative monitoring of mitochondrial components along their consecutive
      enrichment. Pure intact mitochondria were obtained by a multistep approach
      combining differential and density Percoll (ultra) centrifugations. When compared
      with three other intermediate enrichment stages, peptide sequencing and
      quantitative profiling of pure mitochondrial fractions revealed prototypic
      regulatory profiles of per se mitochondrial components. These regulatory profiles
      constitute a distinct cluster defining the mitochondrial compartment and support
      linear discriminant analyses, which rationalized the annotation process. In
      total, this approach experimentally validated the mitochondrial localization of
      512 proteins including 57 proteins that had not been reported for N. crassa
      before. 

PMID- 26215789
TI  - Covalent bridging of surface functionalized Fe3O4 and YPO4:Eu nanostructures for
      simultaneous imaging and therapy.
AB  - Magnetic luminescent hybrid nanostructures (MLHN) have received a great deal of
      attention due to their potential biomedical applications such as thermal therapy,
      magnetic resonance imaging, drug delivery and intracellular imaging. We report
      the development of bifunctional Fe3O4 decorated YPO4:Eu hybrid nanostructures by
      covalent bridging of carboxyl PEGylated Fe3O4 and amine functionalized YPO4:Eu
      particles. The surface functionalization of individual nanoparticulates as well
      as their successful conjugation was evident from Fourier transform infrared
      (FTIR) spectroscopy, dynamic light scattering (DLS), zeta-potential and
      transmission electron microscopy (TEM) studies. X-ray diffraction (XRD) analysis
      reveals the formation of highly crystalline hybrid nanostructures. TEM
      micrographs clearly show the binding/anchoring of 10 nm Fe3O4 nanoparticles onto
      the surface of 100-150 nm rice grain shaped YPO4:Eu nanostructures. These MLHN
      show good colloidal stability, magnetic field responsivity and self-heating
      capacity under an external AC magnetic field. The induction heating studies
      confirmed localized heating of MLHN under an AC magnetic field with a high
      specific absorption rate. Photoluminescence spectroscopy and fluorescence
      microscopy results show optical imaging capability of MLHN. Furthermore,
      successful internalization of these MLHN in the cells and their cellular imaging
      ability are confirmed from confocal microscopy imaging. Specifically, the hybrid
      nanostructure provides an excellent platform to integrate luminescent and
      magnetic materials into one single entity that can be used as a potential tool
      for hyperthermia treatment of cancer and cellular imaging. 

PMID- 26215790
TI  - Ultrasonic washing of textiles.
AB  - We present the results of experimental investigation of ultrasonic washing of
      textiles. The results demonstrate that cavitation bubbles oscillating in acoustic
      fields are capable of removing soils from textiles. Since the washing performance
      is mitigated in a large washing bath when using an ultrasonic transducer, we
      propose a novel washing scheme by combining the ultrasonic vibration with a
      conventional washing method utilizing kinetic energy of textiles. It is shown
      that the hybrid washing scheme achieves a markedly enhanced performance up to 15%
      in comparison with the conventional washing machine. This work can contribute to
      developing a novel laundry machine with reduced washing time and waste water. 

PMID- 26215791
TI  - The danger model: questioning an unconvincing theory.
AB  - Janeway's pattern recognition theory holds that the immune system detects
      infection through a limited number of the so-called pattern recognition receptors
      (PRRs). These receptors bind specific chemical compounds expressed by entire
      groups of related pathogens, but not by host cells (pathogen-associated molecular
      patterns (PAMPs). In contrast, Matzinger's danger hypothesis postulates that
      products released from stressed or damaged cells have a more important role in
      the activation of immune system than the recognition of nonself. These products,
      named by analogy to PAMPs as danger-associated molecular patterns (DAMPs), are
      proposed to act through the same receptors (PRRs) as PAMPs and, consequently, to
      stimulate largely similar responses. Herein, I review direct and indirect
      evidence that contradict the widely accepted danger theory, and suggest that it
      may be false. 

PMID- 26215793
TI  - A Partial Palatal Coverage Overdenture Retained by Zygomatic Implants.
AB  - Prosthodontic rehabilitation of an atrophic edentulous maxilla can be challenging
      and is further complicated when multiple risk factors are present. Fixed
      prostheses require multiple implants for support/retention organized in
      biomechanically favorable positions in order to afford a good prognosis. Such
      suitable implant arrangements in an atrophic edentulous ridge can often be
      difficult to achieve. Removable prostheses require fewer implants for a favorable
      prognosis and can furthermore take advantage of the additional anatomical
      structures for support/retention. This clinical treatment will describe the
      fabrication of a partial palatal coverage overdenture retained by zygomatic
      implants. 

PMID- 26215792
TI  - Controversies concerning thymus-derived regulatory T cells: fundamental issues
      and a new perspective.
AB  - Thymus-derived regulatory T cells (Tregs) are considered to be a distinct T-cell
      lineage that is genetically programmed and specialised for immunosuppression.
      This perspective is based on the key evidence that CD25(+) Tregs emigrate to
      neonatal spleen a few days later than other T cells and that thymectomy of 3-day
      old mice depletes Tregs only, causing autoimmune diseases. Although widely
      believed, the evidence has never been reproduced as originally reported, and some
      studies indicate that Tregs exist in neonates. Thus we examine the consequences
      of the controversial evidence, revisit the fundamental issues of Tregs and
      thereby reveal the overlooked relationship of T-cell activation and Foxp3
      mediated control of the T-cell system. Here we provide a new model of Tregs and
      Foxp3, a feedback control perspective, which views Tregs as a component of the
      system that controls T-cell activation, rather than as a distinct genetically
      programmed lineage. This perspective provides new insights into the roles of self
      reactivity, T cell-antigen-presenting cell interaction and T-cell activation in
      Foxp3-mediated immune regulation.

PMID- 26215794
TI  - Impact of school-based dental program performance on the oral health-related
      quality of life in children.
AB  - OBJECTIVE: To assess the association between the performance of school-based
      dental programs (SBDPs) and oral health-related quality of life (OHRQoL) in
      school children, in the province of Yogyakarta, Indonesia, taking into account
      untreated caries and sociodemographic factors. METHODS: A cross-sectional survey
      was administered with 1906 children aged 12 and participating in SBDPs. Four
      SBDPs were chosen to represent good and poor performance in urban and rural
      areas. Caries was assessed using World Health Organization (WHO) criteria,
      whereas the children were interviewed for the OHRQoL and sociodemographic data.
      The OHRQoL was assessed using the Condition-Specific Child-Oral Impact on Daily
      Performances (CS Child-OIDP) index related to dental caries. RESULTS: The mean CS
      Child-OIDP score was 1.63 (SD +/- 3.20) for good performance SBDP and 6.89 (SD +/
      8.85) for poor performance SBDP. Analysis by negative binomial regression showed
      that being served by a poorly performing SBDP (RR = 4.45, 95% CI = 3.87-5.13),
      and to some extent living in a rural area and being a girl, were significantly
      associated with a greater risk of having a lower quality of life than were the
      counterparts. Untreated caries did not show an association with OHRQoL.
      CONCLUSION: There are substantial indications that SBDP performance is related to
      children's OHRQoL.

PMID- 26215795
TI  - Familial homozygous hypercholesterolemia: When to turn to transplant?

PMID- 26215796
TI  - The influence of pulmonary resistance on the success of pediatric heart
      transplantation: Are there still boundaries?

PMID- 26215797
TI  - Revisiting mycophenolate mofetil for steroid-refractory acute graft-versus-host
      disease: Is higher dosing effective in children?

PMID- 26215798
TI  - Liver transplantation as a definitive treatment for familial
      hypercholesterolemia: A series of 36 cases.
AB  - FH is a genetic disorder characterized by an increase in serum LDL and total
      cholesterol values. The afflicted patients are at increased risk of premature
      atherosclerosis and myocardial infarction. Different treatment modalities are
      present, including pharmacological agents and surgical procedures. The most
      effective method of therapy in refractive cases is liver transplantation. Herein,
      we report our experience on 36 cases of patients with FH undergoing liver
      transplantation in our center, the main referral center of liver transplantation
      in Iran. The clinical findings, hospital courses, post-operative complications,
      and patient follow-up are also described. 

PMID- 26215799
TI  - High blood pressure and sedentary behavior in adolescents are associated even
      after controlling for confounding factors.
AB  - OBJECTIVE: The aim of this study was to determine whether high blood pressure
      (HBP) is associated with sedentary behavior in young people even after
      controlling for potential confounders (gender, age, socioeconomic level, tobacco,
      alcohol, obesity and physical activity). METHODS: In this epidemiological study,
      1231 adolescents were evaluated. Blood pressure was measured with an
      oscillometric device and waist circumference with an inextensible tape. Sedentary
      behavior (watching television, computer use and playing video games) and physical
      activity were assessed by a questionnaire. We used mean and standard deviation to
      describe the statistical analysis, and the association between HBP and sedentary
      behavior was assessed by the chi-squared test. Binary logistic regression was
      used to observe the magnitude of association and cluster analyses (sedentary
      behavior and abdominal obesity; sedentary behavior and physical inactivity).
      RESULTS: HBP was associated with sedentary behaviors [odds ratio (OR) = 2.21, 95%
      confidence interval (CI) = 1.41-3.96], even after controlling for various
      confounders (OR = 1.68, CI = 1.03-2.75). In cluster analysis the combination of
      sedentary behavior and elevated abdominal obesity contributed significantly to an
      increased likelihood of having HBP (OR = 13.51, CI 7.21-23.97). CONCLUSIONS:
      Sedentary behavior was associated with HBP, and excess fat in the abdominal
      region contributed to the modulation of this association.

PMID- 26215800
TI  - Adipose-Derived Mesenchymal Stem Cells Transplantation Alleviates Renal Injury in
      Streptozotocin-Induced Diabetic Nephropathy.
AB  - Previous studies have illustrated that bone marrow-derived mesenchymal stem cell
      (BMMSC) transplantation has therapeutic effects on diabetes and can prevent mice
      from renal damage and diabetic nephropathy (DN). Moreover, adipose-derived MSCs
      possess similar characteristics to BMMSCs. We investigated the effect of ADMSC
      transplantation on streptozotocin (STZ)-induced renal injury. Diabetes was
      induced in rats by STZ injection. After ADMSC treatment, renal histological
      changes and cell apoptosis were evaluated as were the expression of apoptosis
      related proteins, Wnt/beta-catenin pathway members, and klotho levels. We found
      that ADMSCs improved renal histological changes. Next, NRK-52E cells were exposed
      to normal glucose (NG; 5.5 mM glucose plus 24.5 mM mannitol)/high glucose (HG) or
      ADMSCs, and then measured for changes in the aforementioned proteins. Similarly,
      changes in these proteins were also determined following transient transfection
      of klotho siRNA. We found that both ADMSC transplantation and co-incubation
      reduced the rate of cellular apoptosis, decreased Bax and Wnt/beta-catenin
      levels, and elevated Bcl-2 and klotho levels. Interestingly, klotho knockdown
      reversed the effects of ADMSCs on the expression of apoptosis-related proteins
      and Wnt/beta-catenin pathway members. Taken together, ADMSCs transplantation
      might attenuate renal injury in DN via activating klotho and inhibiting the
      Wnt/beta-catenin pathway. This study may provide evidence for the treatment of DN
      using ADMSCs.

PMID- 26215801
TI  - Promotion of presynaptic filament assembly by the ensemble of S. cerevisiae Rad51
      paralogues with Rad52.
AB  - The conserved budding yeast Rad51 paralogues, including Rad55, Rad57, Csm2 and
      Psy3 are indispensable for homologous recombination (HR)-mediated chromosome
      damage repair. Rad55 and Rad57 are associated in a heterodimer, while Csm2 and
      Psy3 form the Shu complex with Shu1 and Shu2. Here we show that Rad55 bridges an
      interaction between Csm2 with Rad51 and Rad52 and, using a fully reconstituted
      system, demonstrate that the Shu complex synergizes with Rad55-Rad57 and Rad52 to
      promote nucleation of Rad51 on single-stranded DNA pre-occupied by replication
      protein A (RPA). The csm2-F46A allele is unable to interact with Rad55, ablating
      the ability of the Shu complex to enhance Rad51 presynaptic filament assembly in
      vitro and impairing HR in vivo. Our results reveal that Rad55-Rad57, the Shu
      complex and Rad52 act as a functional ensemble to promote Rad51-filament
      assembly, which has important implications for understanding the role of the
      human RAD51 paralogues in Fanconi anaemia and cancer predisposition. 

PMID- 26215802
TI  - Sepsis protects the myocardium and other organs from subsequent
      ischaemic/reperfusion injury via a MAPK-dependent mechanism.
AB  - BACKGROUND: Sepsis has been shown to precondition the intact heart against
      ischaemia/reperfusion (IR) injury, and prior endotoxin exposure of cells in in
      vitro models has shown evidence of protection against subsequent simulated
      ischaemia. Our aim in this study is to validate these findings and further
      investigate the signaling pathways involved. METHODS: Adult male Sprague Dawley
      rats were randomised to control (n = 7) or caecal ligation and perforation (CLP)
      induced sepsis (n = 7). Hearts were harvested at 48 h, suspended in Langendorff
      mode and subjected to 30-min global ischaemia followed by 90-min reperfusion. In
      subsequent experiments, designed to determine the mechanisms by which sepsis
      protected against ischaemic injury, endotoxin-stimulated isolated cardiomyocytes,
      pulmonary A549 cells and renal HK2 cells were subjected to normoxic and hypoxic
      conditions. The roles of key pathways, including mitogen-activated protein (MAP)
      kinases extracellular-regulated protein kinase (ERK) 1/2, p38 MAPK (p38), c-Jun
      NH2-terminal protein kinase (JNK)), and nuclear factor-kappaB (NF-kappaB) were
      examined. RESULTS: Systemic sepsis protected isolated hearts from subsequent
      ischaemic/reperfusion-induced injury, enhancing functional recovery on
      reperfusion [developed left ventricular pressure ((d)LVP) mean(SE) 66.63(+/-10.7)
      mmHg vs. 54.13(+/-9.9) mmHg; LVPmax at 60 min 67.29(+/-11.9) vs. 72.48(+/-9.3),
      sepsis vs. control] despite significantly reduced baseline LV function in CLP
      animals (p < 0.001). Septic preconditioning significantly reduced infarct size
      after IR injury (p < 0.05). Endotoxin exposure protected isolated cardiomyocytes
      against hypoxia-induced cell death (p < 0.001). This effect appeared mediated in
      part via the p38, JNK and NF-kappaB pathways, but was independent of the ERK
      pathway, and did not appear to be mediated via HMGB1. The preconditioning effect
      of endotoxin was also demonstrated in isolated kidney and lung cells, suggesting
      that this preconditioning effect of sepsis is not confined to the myocardium.
      CONCLUSIONS: Sepsis preconditions the isolated rat heart against myocardial IR
      injury. These effects appeared to be mediated in part via the p38, JNK and NF
      kappaB and pathways, but were independent of the ERK and HMGB pathways.

PMID- 26215803
TI  - Calcium desensitisation in late polymicrobial sepsis is associated with loss of
      vasopressor sensitivity in a murine model.
AB  - BACKGROUND: Sepsis is characterised by diminished vasopressor responsiveness.
      Vasoconstriction depends upon a balance: Ca(2+)-dependent myosin light-chain
      kinase promotes and Ca(2+)-independent myosin light-chain phosphatase (MLCP)
      opposes vascular smooth muscle contraction. The enzyme Rho kinase (ROK) inhibits
      MLCP, favouring vasoconstriction. We tested the hypothesis that ROK-dependent
      MLCP inhibition was attenuated in late sepsis and associated with reduced
      contractile responses to certain vasopressor agents. METHODS: This is a
      prospective, controlled animal study. Sixteen-week-old C57/BL6 mice received
      laparotomy or laparotomy with caecal ligation and puncture (CLP). Antibiotics,
      fluids and analgesia were provided before sacrifice on day 5. Vasoconstriction of
      the femoral arteries to a range of stimuli was assessed using myography: (i)
      depolarisation with 87 mM K(+) assessed voltage-gated Ca(2+) channels (L-type,
      Cav1.2 Ca(2+) channels (LTCC)), (ii) thromboxane A2 receptor activation assessed
      the activation state of the LTCC and ROK/MLCP axis, (iii) direct PKC activation
      (phorbol-dibutyrate (PDBu), 5 MUM) assessed the PKC/CPI-17 axis independent of
      Ca(2+) entry and (iv) alpha1-adrenoceptor stimulation with phenylephrine (10(-8)
      to 10(-4) M) and noradrenaline (10(-8) to 10(-4) M) assessed the sum of these
      pathways plus the role of the sarcoplasmic reticulum (SR). ROK-dependent MLCP
      activity was indexed by Western blot analysis of P[Thr855]MYPT. Parametric and
      non-parametric data were analysed using unpaired Student's t-tests and Mann
      Whitney tests, respectively. RESULTS: ROK-dependent inhibition of MLCP activity
      was attenuated in both unstimulated (n = 6 to 7) and stimulated (n = 8 to 12)
      vessels from mice that had undergone CLP (p < 0.05). Vessels from CLP mice
      demonstrated reduced vasoconstriction to K(+), thromboxane A2 receptor activation
      and PKC activation (n = 8 to 13; p < 0.05). alpha1-adrenergic responses were
      unchanged (n = 7 to 12). CONCLUSIONS: In a murine model of sepsis, ROK-dependent
      inhibition of MLCP activity in vessels from septic mice was reduced. Responses to
      K(+) depolarisation, thromboxane A2 receptor activation and PKC activation were
      diminished in vitro whilst alpha1-adrenergic responses remained intact.
      Inhibiting MLCP may present a novel therapeutic target to manage sepsis-induced
      vascular dysfunction.

PMID- 26215804
TI  - Attenuated platelet aggregation in patients with septic shock is independent from
      the activity state of myosin light chain phosphorylation or a reduction in Rho
      kinase-dependent inhibition of myosin light chain phosphatase.
AB  - BACKGROUND: Impaired coagulation contributes to the morbidity and mortality
      associated with septic shock. Whether abnormal platelet contraction adds to the
      bleeding tendency is unknown. Platelets contract when Ca(2+)-dependent myosin
      light chain kinase (MLCK) phosphorylates Ser19 of myosin light chain (MLC20),
      promoting actin-myosin cross-bridge cycling. Contraction is opposed when myosin
      light chain phosphatase (MLCP) dephosphorylates MLC20. It is thought that Rho
      kinase (ROK) inhibits MLCP by phosphorylating Thr855 of the regulatory subunit
      MYPT, favouring platelet contraction. This study tested the hypotheses that in
      septic shock, (i) platelet function is inversely correlated with illness severity
      and (ii) ROK-dependent MLCP inhibition and myosin light chain phosphorylation are
      reduced. METHODS: Blood was sampled from non-septic shock patients and patients
      in the first 24 h of septic shock. Platelet function was assessed using whole
      blood impedance aggregation induced by 1) ADP (1.6 and 6.5 MUM), 2) thrombin
      receptor-activating protein (TRAP; 32 MUM), 3) arachidonic acid (500 MUM) and 4)
      collagen (3.2 MUg/ml). Arachidonic acid-induced aggregation was measured in the
      presence of the ROK inhibitor Y27632. Illness severity was evaluated using
      sequential organ failure assessment (SOFA) and acute physiology and chronic
      health evaluation (APACHE) II scores. Western blot analysis of [Ser19]MLC20 and
      [Thr855]MYPT phosphorylation quantified activation and inhibition of platelet
      MLC20 and MLCP, respectively. Data were analysed using Spearman's rank
      correlation coefficient, Student's t-test and Mann-Whitney test; p < 0.05 was
      considered significant. RESULTS: Agonist-induced aggregation was attenuated in
      septic shock patients (n = 22 to 34; p < 0.05). Aggregation correlated inversely
      with SOFA and APACHE II scores (n = 34; p < 0.05). Thr855 phosphorylation of MYPT
      from unstimulated platelets was not decreased in patients with septic shock (n =
      22 to 24). Both septic shock and ROK inhibition attenuated arachidonic acid
      induced platelet aggregation independent of changes in [Ser19]MLC20 and
      [Thr855]MYPT phosphorylation (n = 14). CONCLUSIONS: Impairment of whole blood
      aggregation in patients within the first 24 h of septic shock was correlated with
      SOFA and APACHE II scores. Attenuated aggregation was independent of molecular
      evidence of diminished platelet contraction or reduced ROK inhibition of MLCP.
      Efforts to restore platelet function in septic shock should therefore focus on
      platelet adhesion and degranulation.

PMID- 26215805
TI  - Effect of body position on ventilation distribution during PEEP titration in a
      porcine model of acute lung injury using advanced respiratory monitoring and
      electrical impedance tomography.
AB  - BACKGROUND: Lung failure after acute lung injury remains a challenge in different
      clinical settings. Various interventions for restoration of gas exchange have
      been investigated. Recruitment of collapsed alveoli by positive end expiratory
      pressure (PEEP) titration and optimization of ventilation-perfusion ratio by
      prone positioning have been extensively described in animal and clinical trials.
      This animal study was conducted to investigate the effects of PEEP and
      positioning by means of advanced respiratory monitoring including gas exchange,
      respiratory mechanics, volumetric capnography and electrical impedance
      tomography. METHODS: After induction of acute lung injury by oleic acid and lung
      lavage, 12 domestic pigs were studied in randomly assigned supine or prone
      position during a PEEP titration trial with maximal PEEP of 30 mbar. RESULTS:
      Induction of lung injury resulted in significant deterioration of oxygenation
      [partial pressure of arterial oxygen/inspiratory fraction of oxygen (PaO2/FiO2):
      p = 0.002] and ventilation [partial pressure of arterial carbon dioxide (PaCO2):
      p = 0.002] and elevated alveolar dead-space ratios (Valv/Vte: p = 0.003) in both
      groups. Differences in the prone and the supine group were significant for PaCO2
      at incremental PEEP 10 and 20 and at decremental PEEP 20 (20d) and 10 (10d), for
      PaO2/FiO2 at PEEP 10 and 10d and for alveolar dead space at PEEP 10d. Electrical
      impedance tomography revealed homogenous ventilation distribution in prone
      position during PEEP 20, 30 and 20d. CONCLUSIONS: Prone position leads to
      improved oxygenation and ventilation parameters in a lung injury model.
      Respiratory monitoring with measurement of alveolar dead space and electrical
      impedance tomography may visualize optimized ventilation in a PEEP titration
      trial.

PMID- 26215807
TI  - Cytocam-IDF (incident dark field illumination) imaging for bedside monitoring of
      the microcirculation.
AB  - BACKGROUND: Orthogonal polarized spectral (OPS) and sidestream dark field (SDF)
      imaging video microscope devices were introduced for observation of the
      microcirculation but, due to technical limitations, have remained as research
      tools. Recently, a novel handheld microscope based on incident dark field
      illumination (IDF) has been introduced for clinical use. The Cytocam-IDF imaging
      device consists of a pen-like probe incorporating IDF illumination with a set of
      high-resolution lenses projecting images on to a computer controlled image sensor
      synchronized with very short pulsed illumination light. This study was performed
      to validate Cytocam-IDF imaging by comparison to SDF imaging in volunteers.
      METHODS: This study is a prospective, observational study. The subjects consist
      of 25 volunteers. RESULTS: Sublingual microcirculation was evaluated using both
      techniques. The main result was that Cytocam-IDF imaging provided better quality
      images and was able to detect 30% more capillaries than SDF imaging (total
      vessels density Cytocam-IDF: 21.60 +/- 4.30 mm/mm(2) vs SDF: 16.35 +/- 2.78
      mm/mm(2), p < 0.0001). Comparison of the images showed increased contrast,
      sharpness, and image quality of both venules and capillaries. CONCLUSIONS:
      Cytocam-IDF imaging detected more capillaries and provided better image quality
      than SDF imaging. It is concluded that Cytocam-IDF imaging may provide a new
      improved imaging modality for clinical assessment of microcirculatory
      alterations.

PMID- 26215806
TI  - Shape descriptors of the "never resting" microglia in three different acute brain
      injury models in mice.
AB  - BACKGROUND: The study of microglia and macrophage (M/M) morphology represents a
      key tool to understand the functional activation state and the pattern of
      distribution of these cells in acute brain injury. The identification of reliable
      quantitative morphological parameters is urgently needed to understand these cell
      roles in brain injury and to explore strategies aimed at therapeutically
      manipulating the inflammatory response. METHODS: We used three different
      clinically relevant murine models of focal injury, namely, controlled cortical
      impact brain injury (traumatic brain injury (TBI)) and transient and permanent
      occlusion of middle cerebral artery (tMCAo and pMCAo, respectively). Twenty-four
      hours after injury, M/M cells were labeled by CD11b, and *40 photomicrographs
      were acquired by unbiased sampling of the lesion core using a motorized stage
      microscope. Images were processed with Fiji software to obtain shape descriptors.
      RESULTS: We validated several parameters, including area, perimeter, Feret's
      diameter (caliper), circularity, aspect ratio, and solidity, providing
      quantitative information on M/M morphology over wide tissue portions. We showed
      that the shape descriptors that best represent M/M ramification/elongation are
      area and perimeter, while circularity and solidity provide information on the
      ameboid shape. We also provide evidence of the involvement of different
      populations in local inflammatory events, with macrophages replacing microglia
      into the lesion core when reperfusion does not occur. Analysis of CD45(high)+
      cell morphology, whose shape does not change, did not yield any difference, thus
      confirming the reliability of the approach. CONCLUSIONS: We have defined specific
      morphological features that M/M acquire in response to different acute insults by
      applying a sensitive and readily applicable approach to cell morphological
      analysis in the brain tissue. Potential application of this method can be
      extended to all cell types able to change shape following activation, e.g.,
      astrocytes, or to different disease states, including chronic pathologies.

PMID- 26215808
TI  - Systolic left ventricular function is preserved during therapeutic hypothermia,
      also during increases in heart rate with impaired diastolic filling.
AB  - BACKGROUND: Systolic left ventricular function during therapeutic hypothermia is
      found both to improve and to decline. We hypothesized that this discrepancy would
      depend on the heart rate and the variables used to assess systolic function.
      METHODS: In 16 pigs, cardiac performance was assessed by measurements of invasive
      pressures and thermodilution cardiac output and with 2D strain echocardiography.
      Left ventricle (LV) volumes, ejection fraction (EF), transmitral flow, and
      circumferential and longitudinal systolic strain were measured. Miniaturized
      ultrasonic transducers were attached to the epicardium of the LV to obtain M-mode
      images, systolic thickening, and diastolic thinning velocities and to determine
      LV pressure-wall dimension relationships. Preload recruitable stroke work (PRSW)
      was calculated. Measurements were performed at 38 and 33 degrees C at spontaneous
      and paced heart rates, successively increased in steps of 20 up to the toleration
      limit. Effects of temperature and heart rate were compared in a mixed model
      analysis. RESULTS: Hypothermia reduced heart rate from 87 +/- 10 (SD) to 76 +/-
      11 beats/min without any changes in LV stroke volume, end-diastolic volume, EF,
      strain values, or PRSW. Systolic wall thickening velocity (S') and early
      diastolic wall thinning velocity decreased by approximately 30%, making systolic
      duration longer through a prolonged and slow contraction and changing the
      diastolic filling pattern from predominantly early towards late. Pacing reduced
      diastolic duration much more during hypo- than during normothermia, and combined
      with slow myocardial relaxation, incomplete relaxation occurred with all pacing
      rates. Pacing did not affect S' or PRSW at physiological heart rates, but stroke
      volume, end-diastolic volume, and strain were reduced as a consequence of reduced
      diastolic filling and much more accentuated during hypothermia. At the ultimate
      tolerable heart rate during hypothermia, S' decreased, probably as a consequence
      of myocardial hypoperfusion due to sustained ventricular contraction throughout a
      very short diastole. CONCLUSIONS: Systolic function was maintained at
      physiological heart rates during therapeutic hypothermia. Reduced tolerance to
      increases in heart rate was caused by lack of ventricular filling due to
      diastolic dysfunction and shorter diastolic duration.

PMID- 26215809
TI  - Angiotensin-(1-7) improves oxygenation, while reducing cellular infiltrate and
      fibrosis in experimental Acute Respiratory Distress Syndrome.
AB  - BACKGROUND: The renin-angiotensin system (RAS) plays a role in the pathogenesis
      of ARDS, Angiotensin II (Ang-II) contributing to the pathogenesis of inflammation
      and fibrogenesis. Angiotensin-(1-7) (Ang-(1-7)) may antagonize the effects of Ang
      II. This study was aimed at evaluating the potential for Ang-(1-7) to reduce
      injury, inflammation and fibrosis in an experimental model of ARDS in the acute
      and late phases. METHODS: Male Sprague Dawley rats underwent an instillation of
      0.1 M hydrochloric acid (HCl, 2.5 ml/kg) into the right bronchus. In an acute
      ARDS study, acid-injured rats were subjected to high stretch mechanical
      ventilation (18 ml/kg) for 5 h and randomized to receive an intravenous infusion
      of either vehicle (saline), Ang-(1-7) at low dose(0.27 MUg/kg/h) (ALD), or high
      dose (60 MUg/kg/h) (AHD) starting simultaneously with injury or 2 h afterwards.
      Arterial blood gas analysis and bronchoalveolar lavage (BAL) were performed to
      assess the injury. For the late ARDS study, after HCl instillation rats were
      randomized to either vehicle or high dose Ang-(1-7) (300 MUg/kg/day) infused by
      mini osmotic pumps for two weeks, and lung hydroxyproline content measured.
      RESULTS: In the acute ARDS study, Ang-(1-7) led to a significant improvement in
      oxygenation (PaO2/FiO2 : vehicle 359 +/- 86; ALD 436 +/- 72; AHD 44 442 +/- 56;
      ANOVA p = 0.007) and reduced white blood cells counts (vehicle 4,519 +/- 2,234;
      ALD 2,496 +/- 621; AHD 2,744 +/- 119/mm(3); ANOVA p = 0.004). Only treatment with
      high dose Ang-(1-7) reduced inflammatory cell numbers in BAL (vehicle 127 +/- 34;
      AHD 96 +/- 34/ MUl; p = 0.033). Interestingly also delayed administration of Ang
      (1-7) was effective in reducing injury. In later ARDS, Ang-(1-7) decreased
      hydroxyproline content (649 +/- 202 and 1,117 +/- 297 MUg/lung; p < 0.05).
      CONCLUSIONS: Angiotensin-(1-7), decreased the severity of acute lung injury and
      inflammation induced by combined acid aspiration and high stretch ventilation.
      Furthermore, continuous infusion of Ang-(1-7) reduced lung fibrosis 2 weeks
      following acid aspiration injury. These results call for further research on Ang
      (1-7) as possible therapy for ARDS.

PMID- 26215810
TI  - Effects of norepinephrine on tissue perfusion in a sheep model of intra-abdominal
      hypertension.
AB  - BACKGROUND: The aim of the study was to describe the effects of intra-abdominal
      hypertension (IAH) on regional and microcirculatory intestinal blood flow, renal
      blood flow, and urine output, as well as their response to increases in blood
      pressure induced by norepinephrine. METHODS: This was a pilot, controlled study,
      performed in an animal research laboratory. Twenty-four anesthetized and
      mechanically ventilated sheep were studied. We measured systemic hemodynamics,
      superior mesenteric and renal blood flow, villi microcirculation, intramucosal
      arterial PCO2, urine output, and intra-abdominal pressure. IAH (20 mm Hg) was
      generated by intraperitoneal instillation of warmed saline. After 1 h of IAH,
      sheep were randomized to IAH control (n = 8) or IAH norepinephrine (n = 8)
      groups, for 1 h. In this last group, mean arterial pressure was increased about
      20 mm Hg with norepinephrine. A sham group (n = 8) was also studied. Fluids were
      administered to prevent decreases in cardiac output. Differences between groups
      were analyzed with two-way repeated measures of analysis of variance (ANOVA).
      RESULTS: After 2 h of IAH, abdominal perfusion pressure decreased in IAH control
      group compared to IAH norepinephrine and sham groups (49 +/- 11, 73 +/- 11, and
      86 +/- 15 mm Hg, P < 0.0001). There were no differences in superior mesenteric
      artery blood flow, intramucosal-arterial PCO2, and villi microcirculation among
      groups. Renal blood flow (49 +/- 30, 32 +/- 24, and 102 +/- 45 mL.min(-1).kg(-1),
      P < 0.0001) and urinary output (0.3 +/- 0.1, 0.2 +/- 0.2, and 1.0 +/- 0.6 mL.h(
      1).kg(-1), P < 0.0001) were decreased in IAH control and IAH norepinephrine
      groups, compared to the sham group. CONCLUSIONS: In this experimental model of
      IAH, the gut and the kidney had contrasting responses: While intestinal blood
      flow and villi microcirculation remained unchanged, renal perfusion and urine
      output were severely compromised.

PMID- 26215811
TI  - An improved mounting device for attaching intracranial probes in large animal
      models.
AB  - BACKGROUND: The rigid support of intracranial probes can be difficult when using
      animal models, as mounting devices suitable for the probes are either not
      available, or designed for human use and not suitable in animal skulls. A cheap
      and reliable mounting device for securing intracranial probes in large animal
      models is described. METHODS: Using commonly available clinical consumables, a
      universal mounting device for securing intracranial probes to the skull of large
      animals was developed and tested. RESULTS: A simply made mounting device to hold
      a variety of probes from 500 MUm to 1.3 mm in diameter to the skull was
      developed. The device was used to hold probes to the skulls of sheep for up to 18
      h. No adhesives or cements were used. CONCLUSION: The described device provides a
      reliable method of securing probes to the skull of animals.

PMID- 26215812
TI  - Why do they die? Comparison of selected aspects of organ injury and dysfunction
      in mice surviving and dying in acute abdominal sepsis.
AB  - BACKGROUND: The mechanisms of sepsis mortality remain undefined. While there is
      some evidence of organ damage, it is not clear whether this damage alone is
      sufficient to cause death. Therefore, we aimed to examine contribution of organ
      injury/dysfunction to early deaths in the mouse abdominal sepsis. METHODS: Female
      OF-1 mice underwent either medium-severity cecal ligation and puncture (CLP-Only)
      or non-lethal CLP-ODam (CLP with cisplatin/carbontetrachloride to induce
      survivable hepatotoxicity and nephrotoxicity). In the first experiment, blood was
      collected daily from survivors (SUR; CLP-Only and CLP-ODam groups) or until early
      death (DIED; CLP-Only). In the second experiment (CLP-Only), early outcome was
      prospectively predicted based on body temperature (BT) and pairs of mice
      predicted to survive (P-SUR) and die (P-DIE) were sacrificed post-CLP. The
      overall magnitude of organ injury/dysfunction was compared in retrospectively and
      prospectively stratified mice. RESULTS: At day 7 post-CLP, survival in CLP-Only
      was 48%, while CLP-ODam was non-lethal. In CLP-Only mice within 24 h of death,
      urea increased to 78 (versus 40 mg/dl in SUR), ALT to 166 (vs. 108 U/l), LDH to
      739 (vs. 438 U/l) and glucose declined to 43 (vs. 62 mg/dl). In CLP-ODam,
      hypoglycemia was exacerbated (by 1.5-fold) and ALT and LDH were 20- and 8-fold
      higher versus DIED (CLP-Only) mice. In CLP-Only, predicted deaths (P-DIE) were
      preceded by a significant rise only in cystatin C (268 vs. 170 ng/ml in P-SUR)
      but not in creatinine and troponin I. Respiratory function of mitochondria in the
      liver and kidney of P-SUR and P-DIE CLP-Only mice was not impaired (vs. controls)
      and ATP level in organs remained similar among all groups. Histologic injury
      scores in the liver, kidney, heart and lung showed no major disparities among
      dying, surviving and control mice. CONCLUSIONS: In CLP-Only mice, although the
      deregulation of parameters indicative of organ injury/dysfunction was greater in
      dying versus surviving mice, it never exceeded the changes in surviving CLP-ODam
      animals, and it was not followed by histopathological damage and/or mitochondrial
      dysfunction. This shows that interpretation of the contribution of the organ
      injury/dysfunction to early deaths in the CLP model is not straightforward and
      depends on the pathophysiological origin of the profiled disturbances.

PMID- 26215813
TI  - Effects of early hemodynamic resuscitation on left ventricular performance and
      microcirculatory function during endotoxic shock.
AB  - BACKGROUND: Microcirculation and macrohemodynamics are severely compromised
      during septic shock. However, the relationship between these two compartments
      needs to be further investigated. We hypothesized that early resuscitation
      restores left ventricular (LV) performance and microcirculatory function but
      fails to prevent metabolic disorders. We studied the effects of an early
      resuscitation protocol (ERP) on LV pressure/volume loops-derived parameters,
      sublingual microcirculation, and metabolic alterations during endotoxic shock.
      METHODS: Twenty-five pigs were randomized into three groups: LPS group:
      Escherichia coli lipopolysaccharide (LPS); ERP group: LPS + ERP based on volume
      expansion, dobutamine, and noradrenaline infusion; Sham group. LV pressure/volume
      derived parameters, systemic hemodynamics, sublingual microcirculation, and
      metabolic profile were assessed at baseline and after completing the
      resuscitation protocol. RESULTS: LPS significantly decreased LV end-diastolic
      volume, myocardial contractility, stroke work, and cardiac index (CI). Early
      resuscitation preserved preload, and myocardial contractility, increased CI and
      heart rate (p < .05). LPS severely diminished sublingual microvascular flow index
      (MFI), perfused vascular density (PVD), and the proportion of perfused vessels
      (PPV), while increased the heterogeneity flow index (HFI) (p < .05). Despite MFI
      was relatively preserved, MVD, PVD, and HFI were significantly impaired after
      resuscitation (p < .05). The macro- and microcirculatory changes were associated
      with increased lactic acidosis and mixed venous O2 saturation when compared to
      baseline values (p < .05). The scatter plot between mean arterial pressure (MAP)
      and MFI showed a biphasic relationship, suggesting that the values were within
      the limits of microvascular autoregulation when MAP was above 71 +/- 6 mm Hg (R
      (2) = 0.63). CONCLUSIONS: Early hemodynamic resuscitation was effective to
      restore macrohemodynamia and myocardial contractility. Despite MAP and MFI were
      relatively preserved, the persistent microvascular dysfunction could explain
      metabolic disorders. The relationship between micro- and systemic hemodynamia and
      their impact on cellular function and metabolism needs to be further studied
      during endotoxic shock.

PMID- 26215814
TI  - A randomized clinical trial of ascorbic acid in open abdominal aortic aneurysm
      repair.
AB  - BACKGROUND: Open AAA repair is associated with ischaemia-reperfusion injury where
      systemic inflammation and endothelial dysfunction can lead to multiple organ
      injury including acute lung injury. Oxidative stress plays a role that may be
      inhibited by ascorbic acid. METHODS: A double blind, allocation concealed,
      randomized placebo-controlled trial was performed to test the hypothesis that a
      single bolus dose (2g) of intra-operative parenteral ascorbic acid would
      attenuate biomarkers of ischaemia-reperfusion injury in patients undergoing
      elective open AAA repair. RESULTS: Thirty one patients completed the study; 18
      received placebo and 13 ascorbic acid. Groups were comparable demographically.
      Open AAA repair caused an increase in urinary Albumin:Creatinine Ratio (ACR) as
      well as plasma IL-6 and IL-8. There was a decrease in exhaled breath pH and
      oxygenation. Lipid hydroperoxides were significantly higher in the ascorbic acid
      group following open AAA repair. There were no other differences between the
      ascorbic acid or placebo groups up to 4 hours after removal of the aortic
      clamping. CONCLUSIONS: Open AAA repair caused an increase in markers of systemic
      endothelial damage and systemic inflammation. Administration of 2g parenteral
      ascorbic acid did not attenuate this response and with higher levels of lipid
      hydroperoxides post-operatively a pro-oxidant effect could not be excluded. TRIAL
      REGISTRATION: ISRCTN27369400.

PMID- 26215815
TI  - An authentic animal model of the very preterm infant on nasal continuous positive
      airway pressure.
AB  - BACKGROUND: The surge in uptake of nasal continuous positive airway pressure
      (CPAP) for respiratory support in preterm infants has occurred in the absence of
      an authentic animal model. Such a model would allow investigation of research
      questions of physiological and therapeutic importance. We therefore aimed to
      develop a preterm lamb model of the non-intubated very preterm infant on CPAP.
      METHODS: After staged exteriorisation and instrumentation, preterm lambs were
      delivered from anaesthetised ewes at 131 to 133 days gestation. Via a single
      nasal prong (4-mm internal diameter, 6- to 7-cm depth), positive pressure was
      delivered from the outset, with nasal intermittent positive pressure ventilation
      (NIPPV) used until transition to nasal CPAP was attempted, and periodically
      thereafter for hypoventilation. Caffeine and doxapram were used as respiratory
      stimulants. Gastric distension was prevented with an oesophageal balloon.
      Cardiorespiratory parameters and results of arterial blood gas analyses were
      monitored throughout the study period, which continued for 150 min after first
      transition to CPAP. RESULTS: Ten preterm lambs were studied, at gestation 132 +/-
      1 days (mean +/- SD) and birth weight 3.6 +/- 0.45 kg. After stabilisation on
      NIPPV, transition to nasal CPAP was first attempted at 28 +/- 11 min. There was
      transient respiratory acidosis, with gradual resolution as spontaneous
      respiratory activity increased. In the final hour, 79% +/- 33% of time was spent
      on CPAP alone, with typical respiratory rates around 60 breaths per minute. PaCO2
      at end-experiment was 58 +/- 36 mmHg. CONCLUSIONS: Non-intubated preterm lambs
      can be effectively transitioned to nasal CPAP soon after birth. This animal model
      will be valuable for further research.

PMID- 26215816
TI  - Critical illness-induced bone loss is related to deficient autophagy and histone
      hypomethylation.
AB  - BACKGROUND: Survivors of critical illness are at increased risk of fractures.
      This may be due to increased osteoclast formation during critical illness,
      leading to trabecular bone loss. Such bone loss has also been observed in Paget's
      disease, and has been related to deficient autophagy. Deficient autophagy has
      also been documented in vital organs and skeletal muscle of critically ill
      patients. The objective of this study was to investigate whether deficient
      autophagy can be linked to critical illness-induced bone loss. METHODS:
      Osteoclasts grown in vitro and their precursor cells isolated from peripheral
      blood of critically ill patients and from matched healthy volunteers were
      analysed for the expression of autophagy genes (SQSTM1, Atg3 and Atg7), and
      proteins (p62, Atg-5, and microtubule-associated protein light chain 3-II (LC3
      II)) and for autophagy and epigenetic signalling factors via PCR arrays and were
      treated with the autophagy inducer rapamycin. The effect of rapamycin was also
      investigated at the tissue level in an in vivo rabbit model of critical illness.
      RESULTS: Many more osteoclasts formed in vitro from the blood precursor cells
      isolated from critically ill patients, which accumulated p62, and displayed
      reduced expression of Atg5, Atg7, and LC3-II compared to healthy controls,
      suggesting deficient autophagy, whilst addition of rapamycin reduced osteoclast
      formation. PCR arrays revealed a down-regulation of histone methyltransferases
      coupled with an up-regulation of negative regulators of autophagy. Critically ill
      rabbits displayed a reduction in trabecular and cortical bone, which was rescued
      with rapamycin. CONCLUSIONS: Deficient autophagy in osteoclasts and their blood
      precursor cells at least partially explained aberrant osteoclast formation during
      critical illness and was linked to global histone hypomethylation. Treatment with
      the autophagy activator Rapamycin reduced patient osteoclast formation in vitro
      and reduced the amount of bone loss in critically ill rabbits in vivo. These
      findings may help to develop novel therapeutic targets to prevent critical
      illness-induced bone loss.

PMID- 26215817
TI  - Interactions between rat alveolar epithelial cells and bone marrow-derived
      mesenchymal stem cells: an in vitro co-culture model.
AB  - BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) reduced the
      severity of acute lung injury after transplantation in multiple experimental
      studies, and several paracrine soluble factors secreted by the cells likely
      contribute to their therapeutic effect. The direct interactions between BMSCs and
      alveolar epithelial cells (AECs) may be an important part of their beneficial
      effects. Therefore, we assessed the interactions between BMSCs and AECs using a
      co-culture model of these two cell types from rats. METHODS: BMSCs and AECs were
      co-cultured using a Transwell system under the following conditions: (1)
      separated co-culture-AECs seeded on the insert and BMSCs in the base of the well;
      and (2) mixed co-culture-AECs on top of the monolayer of BMSCs on the culture
      insert and no cells in the base of the well. After 21 days of culture, the cells
      on the membrane of the culture insert were fixed and stained with antibodies
      against the receptor for advanced glycation end-products (RAGE), surfactant
      protein D (SP-D), and zona occludens protein-1, and then analyzed by confocal
      microscopy. RESULTS: In the separated co-culture condition, the phenotype of the
      AECs was maintained for 21 days, and cluster formation of SP-D-positive cells was
      induced in the AEC monolayer. We also found cluster formations of phospholipid
      positive cells covered with RAGE-positive epithelial cells. In the mixed co
      culture condition, the BMSCs induced alveolar-like structures covered with an
      epithelial cell layer. To determine the effect of keratinocyte growth factor
      (KGF) on this three-dimensional structure formation, we treated the mixed co
      cultures with siRNA for KGF. While KGF siRNA treatment induced a significant
      reduction in surfactant protein transcript expression, formation of the alveolar
      like structure was unaffected. We also assessed whether Gap26, a functional
      inhibitor of connexin-43, could mitigate the effect of the BMSCs on the AECs.
      However, even at 300 MUM, Gap26 did not inhibit formation of the alveolar-like
      structure. CONCLUSIONS: BMSCs release soluble factors that help maintain and
      sustain the AEC phenotype for 21 days, and direct interaction between these two
      cell types can induce a cyst-like, three-dimensional structure covered with AECs.

PMID- 26215818
TI  - Alveolar instability (atelectrauma) is not identified by arterial oxygenation
      predisposing the development of an occult ventilator-induced lung injury.
AB  - BACKGROUND: Improperly set mechanical ventilation (MV) with normal lungs can
      advance lung injury and increase the incidence of acute respiratory distress
      syndrome (ARDS). A key mechanism of ventilator-induced lung injury (VILI) is an
      alteration in alveolar mechanics including alveolar instability or
      recruitment/derecruitment (R/D). We hypothesize that R/D cannot be identified by
      PaO2 (masking occult VILI), and if protective ventilation is not applied, ARDS
      incidence will increase. METHODS: Sprague-Dawley rats (n = 8) were anesthetized,
      surgically instrumented, and placed on MV. A thoracotomy was performed and an in
      vivo microscope attached to the pleural surface of the lung with baseline dynamic
      changes in alveolar size during MV recorded. Alveolar instability was induced by
      intra-tracheal instillation of Tween and alveolar R/D identified as a marked
      change in alveolar size from inspiration to expiration with increases in positive
      end-expiratory pressure (PEEP) levels. RESULTS: Despite maintaining a clinically
      acceptable PaO2 (55-80 mmHg), the alveoli remained unstable with significant R/D
      at low PEEP levels. Although PaO2 consistently increased with an increase in
      PEEP, R/D did not plateau until PEEP was >9 cmH2O. CONCLUSIONS: PaO2 remained
      clinically acceptable while alveolar instability persisted at all levels of PEEP
      (especially PEEP <9 cmH2O). Therefore, PaO2 levels cannot be used reliably to
      guide protective MV strategies or infer that VILI is not occurring. Using PaO2 to
      set a PEEP level necessary to stabilize the alveoli could underestimate the
      potential for VILI. These findings highlight the need for more accurate marker(s)
      of alveolar stability to guide protective MV necessary to prevent VILI.

PMID- 26215819
TI  - Prone position ameliorates lung elastance and increases functional residual
      capacity independently from lung recruitment.
AB  - BACKGROUND: Prone position is used to recruit collapsed dependent lung regions
      during severe acute respiratory distress syndrome, improving lung elastance and
      lung gas content. We hypothesised that, in the absence of recruitment, prone
      position would not result in any improvement in lung mechanical properties or gas
      content compared to supine position. METHODS: Ten healthy pigs under general
      anaesthesia and paralysis underwent a pressure-volume curve of the respiratory
      system, chest wall and lung in supine and prone positions; the respective
      elastances were measured. A lung computed tomography (CT) scan was performed in
      the two positions to compute gas content (i.e. functional residual capacity
      (FRC)) and the distribution of aeration. Recruitment was defined as a percentage
      change in non-aerated lung tissue compared to the total lung weight. RESULTS: Non
      aerated (recruitable) lung tissue was a small percentage of the total lung tissue
      weight in both positions (4 +/- 3 vs 1 +/- 1 %, supine vs prone, p = 0.004). Lung
      elastance decreased (20.5 +/- 1.8 vs 15.5 +/- 1.6 cmH2O/l, supine vs prone, p <
      0.001) and functional residual capacity increased (380 +/- 82 vs 459 +/- 60 ml,
      supine vs prone, p = 0.025) in prone position; specific lung elastance did not
      change (7.0 +/- 0.5 vs 6.5 +/- 0.5 cmH2O, supine vs prone, p = 0.24). Lung
      recruitment was low (3 +/- 2 %) and was not correlated to increases in functional
      residual capacity (R (2) 0.2, p = 0.19). A higher amount of well-aerated and a
      lower amount of poorly aerated lung tissue were found in prone position.
      CONCLUSIONS: In healthy pigs, prone position ameliorates lung mechanical
      properties and increases functional residual capacity independently from lung
      recruitment, through a redistribution of lung aeration.

PMID- 26215820
TI  - Atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical
      ventilation in rats.
AB  - BACKGROUND: Patients with acute respiratory distress syndrome receiving
      mechanical ventilation show inhomogeneous lung aeration. Atelectasis during
      uneven mechanical ventilation leads to alveolar hypoxia and could therefore
      result in lung inflammation and injury. We aimed to elucidate whether and how
      atelectasis causes alveolar hypoxia-induced inflammation during uneven mechanical
      ventilation in an open-chest differential-ventilation rat model. METHODS: We
      first investigated inflammatory and histological changes in the bilateral lungs
      of unilaterally ventilated rats, in which the right lung was atelectatic and the
      left lung was ventilated with high tidal volume (HTV). In the next series, we
      investigated the effects of normal tidal volume (NTV) ventilation of the right
      lungs with 60 % O2 or 100 % N2 during HTV ventilation of the left lungs. Then,
      proinflammatory cytokine secretions were quantified from murine lung epithelial
      (MLE15) and murine alveolar macrophage (MH-S) cells cultured under a hypoxic
      condition (5 % O2) mimicking atelectasis. Further, activities of nuclear factor
      (NF)-kappaB and hypoxia-inducible factor (HIF)-1 were assessed in the
      nonventilated atelectatic lung and MLE15 cells cultured under the hypoxic
      condition. Finally, effects of NF-kappaB inhibition and HIF-1alpha knockdown on
      the cytokine secretions from MLE15 cells cultured under the hypoxic condition
      were assessed. RESULTS: The nonventilated atelectatic lungs showed inflammatory
      responses and minimal histological changes comparable to those of the HTV
      ventilated lungs. NTV ventilation with 60 % O2 attenuated the increase in
      chemokine (C-X-C motif) ligand (CXCL)-1 secretion and neutrophil accumulation
      observed in the atelectatic lungs, but that with 100 % N2 did not. MLE15 cells
      cultured with tumor necrosis factor (TNF)-alpha under the hypoxic condition
      showed increased CXCL-1 secretion. NF-kappaB and HIF-1alpha were activated in the
      nonventilated atelectatic lungs and MLE15 cells cultured under the hypoxic
      condition. NF-kappaB inhibition abolished the hypoxia-induced increase in CXCL-1
      secretion from MLE15 cells, while HIF-1alpha knockdown augmented it. CONCLUSIONS:
      Atelectasis causes alveolar hypoxia-induced inflammatory responses including NF
      kappaB-dependent CXCL-1 secretion from lung epithelial cells. HIF-1 activation in
      lung epithelial cells is an anti-inflammatory response to alveolar hypoxia in
      atelectatic lungs.

PMID- 26215821
TI  - Scavenging reactive oxygen species using tempol in the acute phase of renal
      ischemia/reperfusion and its effects on kidney oxygenation and nitric oxide
      levels.
AB  - BACKGROUND: Renal ischemia/reperfusion (I/R) injury is commonly seen in kidney
      transplantation and affects the allograft survival rates. We aimed to test our
      hypothesis that scavenging reactive oxygen species (ROS) with tempol would
      protect renal oxygenation and nitric oxide (NO) levels in the acute phase of
      renal I/R. METHODS: Rats were randomly divided: (1) no I/R, no tempol; (2) no
      I/R, but with tempol; (3) I/R without tempol; and (4) I/R with tempol. I/R was
      induced by 30-min clamping of the renal artery. Tempol (200 MUmol/kg/h/i.v) was
      administered 15 min prior to I/R. RESULTS: I/R without tempol led to a
      significant decrease in renal oxygen delivery and microvascular oxygenation.
      Tempol, however, protected renal oxygenation after I/R. At R90, the creatinine
      clearance rate was lower in the I/R-subjected group that did not receive tempol
      compared to that in the other groups. I/R injury without tempol treatment led to
      a significant increase in tissue malondialdehyde levels and a significant
      decrease in tissue NO levels. Tempol administration before I/R could prevent
      oxidative stress and altered tissue NO levels. CONCLUSIONS: This underscores that
      unbalance between oxygen, NO, and ROS forms an important component of the
      pathogenesis of I/R-induced AKI and should therefore be taken into account when
      designing a prevention/treatment strategy for renal I/R injury in
      transplantation.

PMID- 26215822
TI  - Analysis of the influence of antithrombin on microvascular thrombosis: anti
      inflammation is crucial for anticoagulation.
AB  - PURPOSE: Microvascular thrombosis during septic conditions is of essential
      clinical relevance, but the pathomechanisms are not yet completely understood.
      The purpose of this study was to study the distinguished differentiation of the
      interactions of inflammation and coagulation using antithrombin (AT), a mediator
      of anticoagulation and anti-inflammation. METHODS: Using a thrombosis model in a
      cremaster muscle preparation of male C57Bl/6J mice (n = 83), we quantitatively
      assessed microvascular thrombus formation by using intravital fluorescence
      microscopy. Experimental groups consisted of animals treated with AT or with
      tryptophan(49)-blocked AT (TrypAT), which exerts only anticoagulant but no anti
      inflammatory effects. To further see whether endothelial glycosaminoglycan (GAG)
      binding with consecutive prostacyclin (PGI2) release is mandatory for the
      anticoagulant process of AT, animals were administered heparin or indomethacin
      either alone or in combination with AT. RESULTS: The antithrombotic capacity of
      AT significantly differs in the experimental groups in which anti-inflammation
      was antagonized. This is given by the significantly prolonged occlusion times (p
      < 0.05) and higher patency rates in case of application of AT alone; while all
      other groups in which the anti-inflammatory action of AT was blocked by TrypAT,
      heparin or indomethacin revealed thrombus kinetics comparable to controls.
      CONCLUSIONS: The anti-inflammatory influence of AT is essentially linked to its
      anticoagulant effect in the microvascular system. Those specifications of the
      active profile of AT characterize the intimate interactions of the anticoagulant
      and anti-inflammatory pathways. This might be of relevance for AT as a
      therapeutic agent in critically diseased patients and the clinical understanding
      of microvascular thrombosis.

PMID- 26215823
TI  - Impairment of neutrophilic glucocorticoid receptor function in patients treated
      with steroids for septic shock.
AB  - BACKGROUND: Glucocorticoid (GC) treatment has variable effect in sepsis. This may
      be explained by decreased expression or function of the glucocorticoid receptor
      (GR). The aim of this study was to determine GR expression and binding capacity
      in patients during and after sepsis. METHODS: In this prospective, non
      interventional clinical study, peripheral blood and clinical data were collected
      from 20 adult patients at five timepoints during sepsis and 5-13 months after
      recovery. GR expression and binding capacity were assessed by flow cytometry.
      RESULTS: GR expression was higher in T lymphocytes from patients with septic
      shock compared to healthy subjects (p = 0.01). While there was no difference in
      GR expression between GC-treated and non-treated patients, GR binding capacity
      was lower in GC-treated patients at admission compared to healthy subjects (p <=
      0.03). After the acute inflammation inflammatory phase, GR binding capacity was
      still lower in neutrophils of GC-treated patients, compared to healthy subjects
      (p = 0.01). On admission, GR binding capacity in T lymphocytes and neutrophils
      was inversely correlated with noradrenaline dose and lactate (p <= 0.03).
      CONCLUSIONS: Our data suggest that GR expression is increased in T lymphocytes
      during septic shock regardless of GC treatment, while GR binding capacity is
      decreased in neutrophils in GC-treated patients. As neutrophils are the
      predominant circulating leucocyte in septic shock, their decreased GR binding
      capacity may impede the response to exogenous or endogenous glucocorticoids.

PMID- 26215824
TI  - Effects of metals on earthworm life cycles: a review.
AB  - Earthworms are abundant and ecologically very important organisms in the soil
      ecosystem. Impacts by pollutants on earthworm communities greatly influence the
      fertility of the terrestrial environment. In ecotoxicology, earthworms are good
      indicators of metal pollution. The observed median lethal concentrations (LC50)
      and the effective concentrations that cause 50% reduction of earthworm growth and
      reproduction (EC50) are referred to as toxicity concentrations or endpoints. In
      addition, the 'no observed effective concentration' (NOEC) is the estimation of
      the toxicity of metals on earthworms expressed as the highest concentration
      tested that does not show effects on growth and reproduction compared to
      controls. This article reviews the ecotoxicological parameters of LC50, EC50 and
      NOEC of a set of worms exposed to a number of metals in various tested media. In
      addition, this article reviews metal accumulation and the influences of soil
      characteristics on metal accumulation in earthworms. Morphological and
      behavioural responses are often used in earthworm toxicity studies. Therefore,
      earthworm responses due to metal toxicity are also discussed in this article.

PMID- 26215825
TI  - Total iron concentrations in waters and fish tissues in the Nam Theun 2 Reservoir
      area (Lao PDR).
AB  - Data on total iron concentrations in waters and freshwater fish tissues in man
      made reservoirs are scarce, especially in Southeast Asia. Changes in total iron
      concentrations in water and in fish tissues were studied after the impoundment of
      the Nam Theun 2 Reservoir (central Lao PDR). Water quality parameters were
      monitored at 11 stations (reservoir, upstream area and downstream areas) from
      2008 to 2010. In 2009 and 2010, total iron concentrations were measured in three
      different fish tissues (viscera, gills and flesh) from 14 species belonging to
      the omnivorous and carnivorous feeding groups. The results indicated that iron
      concentrations in the water were influenced by the reservoir impoundment during
      the first year after the creation of the reservoir. Intra-annual variations of
      the total iron concentration in these waters appeared to be driven by the soil
      leaching processes mainly during the wet season. In fish, total iron accumulated
      preferentially in viscera, followed by gills and flesh. Iron concentration was
      highly species dependant and related to the ecology of the species whereas
      feeding habits (omnivorous or carnivorous) did not influence total iron
      concentration in fish tissues. Finally, reservoir impoundment did not affect iron
      concentrations in fish from the reservoir and from both downstream areas. 

PMID- 26215826
TI  - Long-term monitoring of western aspen--lessons learned.
AB  - Aspen woodland is an important ecosystem in the western United States. Aspen is
      currently declining in western mountains; stressors include conifer expansion due
      to fire suppression, drought, disease, heavy wildlife and livestock use, and
      human development. Forecasting of tree species distributions under future climate
      scenarios predicts severe losses of western aspen within the next 50 years. As a
      result, aspen has been selected as one of 14 vital signs for long-term monitoring
      by the National Park Service Upper Columbia Basin Network. This article describes
      the development of a monitoring protocol for aspen including inventory mapping,
      selection of sampling locations, statistical considerations, a method for
      accounting for spatial dependence, field sampling strategies, and data
      management. We emphasize the importance of collecting pilot data for use in
      statistical power analysis and semi-variogram analysis prior to protocol
      implementation. Given the spatial and temporal variability within aspen stem size
      classes, we recommend implementing permanent plots that are distributed spatially
      within and among stands. Because of our careful statistical design, we were able
      to detect change between sampling periods with desired confidence and power.
      Engaging a protocol development and implementation team with necessary and
      complementary knowledge and skills is critical for success. Besides the project
      leader, we engaged field sampling personnel, GIS specialists, statisticians, and
      a data management specialist. We underline the importance of frequent
      communication with park personnel and network coordinators. 

PMID- 26215827
TI  - Abutilon indicum L.: a prospective weed for phytoremediation.
AB  - This study was aimed to determine the uptake and accumulation potential of a weed
      (Abutilon indicum L.) for phytoremediation of soil contaminated with cadmium.
      Plants were grown in soil spiked with 0, 2.5, 5, 10, 15, 20, 25 mg/kg Cd,
      individually. Plants sample (root and shoot) were analyzed for Cd content at 30,
      60, and 90 days and accumulation trends were characterized. A steady increase in
      Cd accumulation with increasing metal concentration and exposure period was
      observed for all treatments. Accumulation of Cd in roots was found to be 4.3-7.7
      times higher than that of shoots. Statistically significant difference (P <=
      0.001) in mean metal content in root and shoot at successive days of study was
      recorded. Effect of Cd on growth and physiology was also evaluated. At higher Cd
      levels, root and shoot length and biomass of test plant were reduced
      significantly. Although, growth was delayed initially, it was comparable to
      control at the end of the study. Chlorophyll and proline content declined with
      the increase in Cd concentration at 30 and 60 days after treatment. However, at
      90 days, values were more or less comparable to the control values showing the
      adaptability of test plant in Cd contamination. Considering the accumulation
      ability, BCF >1 (bioconcentration factor) and TF <1 (translocation factor)
      established A. indicum as a potential candidate plant for phytoremediation.
      Hence, phytoremediation employing indigenous weed species like A. indicum can be
      an ecologically viable option for sustainable and cost-effective management of
      heavy metal-contaminated soils. 

PMID- 26215828
TI  - Using detailed monitoring data to simulate spatial sediment loading in a
      watershed.
AB  - The use of watershed models as cost-effective tools to quantify the impact of
      conservation practices on water quality is often constrained by lack of data for
      model parameterization. This study uses short-term (3 years) detailed monitoring
      data to guide spatially distributed model parameterization and modeling analysis
      for suspended sediment in the Upper Esopus Creek Watershed (UECW) that is part of
      the New York City water supply. The calibrated Soil and Water Assessment Tool
      (SWAT) model simulated suspended sediment loading from tributary sub-basins and
      at the watershed outlet that were comparable to field measurements. Model
      simulations estimated that stream channels contributed the majority (85%) of
      stream sediment in the study watershed followed by upland erosion (11%) and point
      sources (4%), consistent with previous estimates and field observations. Long
      term (12 years) simulation of the calibrated model was used to apportion the
      average annual sediment yields from tributary sub-basins which ranged between 12
      and 161 t km(-2) year(-1). Model simulations were also used to understand the
      inter-annual variability and seasonality in suspended sediment loading in the
      study watershed. We demonstrate the wider applicability of short-term detailed
      monitoring for model parameterization and calibration, and long-term simulation
      of water quality using the SWAT model.

PMID- 26215829
TI  - Fluoride estimation and its correlation with other physicochemical parameters in
      drinking water of some areas of Balochistan, Pakistan.
AB  - The fluoride level in drinking water is an important parameter and has to be
      controlled in order to prevent dental and skeletal fluorosis. The objective of
      this study is to assess fluoride content and other water quality parameters in
      the samples taken from open wells, tube wells, and karezes of Mastung, Mangochar,
      and Pringabad areas of Balochistan province. A total number of 96 drinking water
      samples out of 150 were found unfit for human consumption. Area-wise analysis
      show that the samples from 39 sites from Mastung, 12 from Mangochar, and 13 from
      Pringabad were found in the risk of dental fluorosis of mild to severe nature.
      However, 12 sampling sites from Mastung, 8 from Mangochar, and 2 from Pringabad
      were identified as the risks of mottling and skeletal fluorosis or other bone
      abnormalities. The highest concentration of F(-) has been observed as 14 mg L(-1)
      in Mastung. Correlation analysis show that fluoride solubility in drinking water
      is pH dependent; and the salts of Ca(2+), Na(+), K(+), Cl(-), and SO4(2-)
      contribute to attain the favorable pH for dissolution of fluoride compounds in
      drinking water. Principal component analysis shows that the geochemical
      composition of the rocks is only responsible for groundwater contamination. On
      the basis of the results, defloridation of the identified sampling sites and
      continuous monitoring of drinking water at regular basis is recommended at
      government level to avoid further fluorosis risks.

PMID- 26215830
TI  - Retraction Note to: Development of a screening tool to assess the temporal risk
      of pesticides leaching to groundwater using the source, target, vector approach.
      An Irish case study for shallow groundwater.

PMID- 26215831
TI  - Improving Social Determinants of Health: Effectiveness of a Web-Based
      Intervention.
AB  - INTRODUCTION: Although patients who experience health-related social problems
      such as food insecurity are at increased risk for negative health outcomes, there
      are few systems for screening and intervention. The study aimed to determine
      whether a web-based intervention can (1) connect youth to services to address
      these problems and (2) increase their resolution. DESIGN: Prospective
      intervention study. SETTING/PARTICIPANTS: A total of 401 youth, aged 15-25 years,
      from an urban adolescent/young adult clinic were recruited. INTERVENTION: A self
      administered, web-based tool was developed to screen participants for problems in
      nine health-related social domains, identify and provide feedback about potential
      problems, and facilitate a patient-centered selection process of recommended
      local health and human service agencies to assist in addressing selected problems
      (conducted in 2008-2010). Follow-up phone calls 1-2 months later determined if
      patients had contacted recommended agencies and resolved their top-priority
      problem. MAIN OUTCOME MEASURES: Outcome measures included prevalence of
      identified problems, selected problems, and priority problem selected by domain.
      We also examined frequencies of referral agencies contacted and resolution of
      priority problem at time of follow-up analysis conducted in 2011-2013. RESULTS:
      Seventy-eight percent (313/401) of youth selected at least one problem to
      address. The most frequent domains selected as priority were income security
      (21%); nutrition/fitness (15%); and healthcare access (15%). Eighty-three percent
      (259/313) were reached at follow-up; overall, 40% contacted a selected agency and
      47% reported "completely" or "mostly" resolving their priority problem.
      CONCLUSIONS: When provided with services to address health-related social
      problems, the majority of youth choose to receive help, with nearly half
      successfully addressing their priority concern. Further research to understand
      the barriers to contacting and utilizing services is needed. A technology-based
      patient-centered feedback and referral system for social determinants of health
      can facilitate screening and connect patients with resources to address these
      problems.

PMID- 26215832
TI  - Causes of Death Associated With Prolonged TV Viewing: NIH-AARP Diet and Health
      Study.
AB  - INTRODUCTION: TV viewing is the most prevalent sedentary behavior and is
      associated with increased risk of cardiovascular disease and cancer mortality,
      but the association with other leading causes of death is unknown. This study
      examined the association between TV viewing and leading causes of death in the
      U.S. METHODS: A prospective cohort of 221,426 individuals (57% male) aged 50-71
      years who were free of chronic disease at baseline (1995-1996), 93% white, with
      an average BMI of 26.7 (SD=4.4) kg/m(2) were included. Participants self-reported
      TV viewing at baseline and were followed until death or December 31, 2011. Hazard
      ratios (HRs) and 95% CIs for TV viewing and cause-specific mortality were
      estimated using Cox proportional hazards regression. Analyses were conducted in
      2014-2015. RESULTS: After an average follow-up of 14.1 years, adjusted mortality
      risk for a 2-hour/day increase in TV viewing was significantly higher for the
      following causes of death (HR [95% CI]): cancer (1.07 [1.03, 1.11]); heart
      disease (1.23 [1.17, 1.29]); chronic obstructive pulmonary disease (1.28 [1.14,
      1.43]); diabetes (1.56 [1.33, 1.83]); influenza/pneumonia (1.24 [1.02, 1.50]);
      Parkinson disease (1.35 [1.11, 1.65]); liver disease (1.33 [1.05, 1.67]); and
      suicide (1.43 [1.10, 1.85]. Mortality associations persisted in stratified
      analyses with important potential confounders, reducing causation concerns.
      CONCLUSIONS: This study shows the breadth of mortality outcomes associated with
      prolonged TV viewing, and identifies novel associations for several leading
      causes of death. TV viewing is a prevalent discretionary behavior that may be a
      more important target for public health intervention than previously recognized.
      TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00340015.

PMID- 26215833
TI  - Nucleotide Variants of the BH4 Biosynthesis Pathway Gene GCH1 and the Risk of
      Orofacial Clefts.
AB  - A deficiency of GTP cyclohydrolase, encoded by the GCH1 gene, results in two
      neurological diseases: hyperphenylalaninaemia type HPABH4B and DOPA-responsive
      dystonia. Genes involved in neurotransmitter metabolism and motor systems may
      contribute to palatogenesis. The purpose of the study was to analyse polymorphic
      variants of the GCH1 gene as risk factors for non-syndromic cleft lip with or
      without cleft palate (NSCL/P). Genotyping of nine polymorphisms was conducted in
      a group of 281 NSCL/P patients and 574 controls. The GCH1 variant rs17128077 was
      associated with a 1.7-fold higher risk for NSCL/P (95 %CI = 1.224-2.325; p =
      0.001). We also found a significant correlation between the rs8004018 and
      rs17128050 variants and an increased risk of oral clefts (p trend = 0.003 and
      0.004, respectively). The best evidence of the global haplotype association was
      observed for rs17128050 and rs8004018 (p corr = 0.0152). This study demonstrates
      that the risk of NSCL/P is associated with variants of the GCH1 gene related to
      BH4 metabolism and provides some evidence of the relationships between
      morphological/functional shifts in the central nervous system and orofacial
      clefts.

PMID- 26215834
TI  - The Role of PGRN in Alzheimer's Disease.
AB  - Progranulin (PGRN), a multifunctional growth factor expressed in various tissues,
      is involved in a diversity of physiologic and pathological processes, including
      cell proliferation, wound healing, and modulation of inflammation. Interest in
      the role of progranulin in the brain has increased dramatically since mutations
      in GRN, which encodes for the protein PGRN, are associated with the pathogenesis
      of Alzheimer's disease (AD). A great many of studies suggest that PGRN
      participates in AD pathogenesis through diverse pathways, including Abeta
      deposition and clearance, intraneuronal deposition of phosphorylated tau,
      neuroinflammation, and neuronal survival. Decreased GRN mRNA levels can be
      detected in the parietal lobe of patients clinically diagnosed with AD; more
      importantly, emerging data support that serum or plasma PGRN can act as a
      biomarker for AD. By understanding PGRN in a wider context, we may be better able
      to depict its role in AD and then provide a therapeutic strategy for AD.

PMID- 26215835
TI  - Kdm6b and Pmepa1 as Targets of Bioelectrically and Behaviorally Induced Activin A
      Signaling.
AB  - The transforming growth factor-beta (TGF-beta) family member activin A exerts
      multiple neurotrophic and protective effects in the brain. Activin also modulates
      cognitive functions and affective behavior and is a presumed target of
      antidepressant therapy. Despite its important role in the injured and intact
      brain, the mechanisms underlying activin effects in the CNS are still largely
      unknown. Our goal was to identify the first target genes of activin signaling in
      the hippocampus in vivo. Electroconvulsive seizures, a rodent model of
      electroconvulsive therapy in humans, were applied to C57BL/6J mice to elicit a
      strong increase in activin A signaling. Chromatin immunoprecipitation experiments
      with hippocampal lysates subsequently revealed that binding of SMAD2/3, the
      intracellular effectors of activin signaling, was significantly enriched at the
      Pmepa1 gene, which encodes a negative feedback regulator of TGF-beta signaling in
      cancer cells, and at the Kdm6b gene, which encodes an epigenetic regulator
      promoting transcriptional plasticity. Underlining the significance of these
      findings, activin treatment also induced PMEPA1 and KDM6B expression in human
      forebrain neurons generated from embryonic stem cells suggesting interspecies
      conservation of activin effects in mammalian neurons. Importantly, physiological
      stimuli such as provided by environmental enrichment proved already sufficient to
      engender a rapid and significant induction of activin signaling concomitant with
      an upregulation of Pmepa1 and Kdm6b expression. Taken together, our study
      identified the first target genes of activin signaling in the brain. With the
      induction of Kdm6b expression, activin is likely to gain impact on a presumed
      epigenetic regulator of activity-dependent neuronal plasticity.

PMID- 26215836
TI  - Association of Nicotinamide-N-Methyltransferase Gene rs694539 Variant with
      Epilepsy.
AB  - Here, we report the association of the rs694539 variant of nicotinamide-N
      methyltransferase gene with epilepsy in a case-control study of 215 patients with
      epilepsy and 239 healthy controls (chi (2) = 11.641, P = 0.003). The individuals
      with the GG genotype revealed protection against epilepsy (chi (2) = 5.866, P =
      0.015, OR = 0.623, 95 % CI = 0.425-0.915), whereas the individuals with the AA
      genotype showed statistically significant increased risk for epilepsy (chi (2) =
      8.676, P = 0.003, OR = 5.479, 95 % CI = 1.553-19.337). In addition, the G allele
      was protective against epilepsy (chi (2) = 8.676, P = 0.003, OR = 0.183, 95 % CI
      = 0.052-0.644); on the contrary, the A allele was a genetic risk factor for
      epilepsy (chi (2) = 5.866, P = 0.015, OR = 1.604, 95 % CI = 1.093-2.354).
      Stratification analysis revealed that the association was statistically
      significant in male patients with epilepsy (chi (2) = 6.682, P = 0.035). However,
      the statistical power was only 0.33 in female patients with epilepsy (chi (2) =
      5.275, P = 0.072). This finding, for the first time, suggests the involvement of
      the NNMT gene rs694539 variant in the etiology of epilepsy.

PMID- 26215838
TI  - Isolation and Characterization of a Bismuth(II) Radical.
AB  - More than 80 years after Paneth's report of dimethyl bismuth, the first monomeric
      Bi(II) radical that is stable in the solid state has been isolated and
      characterized. Reduction of the diamidobismuth(III) chloride Bi(NON(Ar))Cl
      (NON(Ar)=[O(SiMe2NAr)2](2-); Ar=2,6-iPr2C6H3) with magnesium affords the Bi(II)
      radical Bi(NON(Ar)). X-ray crystallographic measurements are consistent with a
      two-coordinate bismuth in the +2 oxidation state with no short intermolecular
      contacts, and solid-state SQUID magnetic measurements indicate a paramagnetic
      compound with a single unpaired electron. EPR and density functional calculations
      show a metal-centered radical with >90% spin density in a p-type orbital on
      bismuth.

PMID- 26215837
TI  - The Role of Retromer in Alzheimer's Disease.
AB  - The retromer complex is an important component of the endosomal protein sorting
      machinery and mediates protein cargoes from endosomes to the trans-Golgi network
      (TGN) by retrograde pathway or to the cell surface through recycling pathway.
      Studies show that retromer and its receptors can make amyloid precursor protein
      (APP)/beta-site APP-cleaving enzyme 1 (BACE1) away endosomes that reduces the
      production of amyloid beta (Abeta). And, tetramer is also found to regulate
      phagocytic receptors to the plasma membrane of microglia, where some phagocytic
      receptors take part in Abeta clearance. Therefore, disruption of retromer will
      increase the production of Abeta. Recently, a plausible relationship between
      disturbance of retromer and tauopathies is raised. Retromer dysfunction may
      result in decreasing the clearance of extracellular tau and the level of
      cathepsin D, which enables tau-induced neurotoxicity. This review article
      summarizes the structure and function of retromer and its role in pathogenesis of
      AD. In the end, retromer may provide a potential therapeutic strategy for the
      treatment of AD.

PMID- 26215839
TI  - Gastric Fundic Gland Adenocarcinoma With Chief Cell Differentiation.

PMID- 26215840
TI  - Reply: To PMID 24763552.

PMID- 26215841
TI  - Reply: To PMID 25311382.

PMID- 26215842
TI  - WITHDRAWN: Quality Measurement in Gastroenterology: Confessions of a Realist.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published,
      http://dx.doi.org/10.1016/j.cgh.2015.07.033. 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- 26215843
TI  - Recent progress in the treatment of infant acute lymphoblastic leukemia.
AB  - Treatment of infants with acute lymphoblastic leukemia (ALL), especially those
      with mixed lineage leukemia (MLL) rearrangement (MLL-r), which account for
      approximately 80% of cases, is still a major challenge for pediatric
      hematologists and oncologists worldwide. Continuing efforts by collaborative
      clinical study groups in Europe, North America, and Japan have rescued
      approximately half of the MLL-r ALL patients with intensive chemotherapy with or
      without allogeneic hematopoietic stem cell transplantation. Recent progress has
      clarified the unique mechanism of MLL-r ALL: the aberrant methylation and histone
      modifications via DOT1L and other related molecules by MLL fusion proteins lead
      to leukemogenetic gene expression, thus to overt leukemia. In order to overcome
      this dismal subtype of ALL, novel targeted therapy based on leukemia biology is
      urgently needed. Due to the extreme rarity of the disease, collaboration between
      the study groups in Europe (Interfant), North America (Children's Oncology
      Group), and Japan (Japanese Pediatric Leukemia/Lymphoma Study Group) is under
      way. 

PMID- 26215844
TI  - Joint contact forces when minimizing the external knee adduction moment by gait
      modification: A computer simulation study.
AB  - BACKGROUND AND PURPOSE: Gait modification is often used to reduce the external
      knee adduction moment (KAM) in human walking, but the relationship between KAM
      reduction and changes in medial knee joint contact force (JCF) is not well
      established. Our purpose was to examine the limiting case of KAM-based gait
      modification: reducing the KAM as much as possible, and the resulting effects on
      JCF. METHODS: We used musculoskeletal modeling to perform three optimal control
      simulations: normal walking, a modified gait that reduced the KAM as much as
      theoretically possible (Min(KAM) simulation), and a second modified gait that
      minimized the KAM plus the metabolic cost of transport (Min(KAM+CoT) simulation).
      RESULTS: The two modified gaits both reduced the peak KAM from normal walking (
      82% for Min(KAM) simulation, -74% for Min(KAM+CoT) simulation) by increasing
      trunk lean, toe-out, and step width, and reducing knee flexion. Even though the
      Min(KAM+CoT) simulation had the larger KAM, it had a greater reduction in peak
      medial JCF (-27%) than the Min(KAM) simulation (-15%) because it reduced the KAM
      using less knee muscle activity. These results were qualitatively robust to a
      sensitivity analysis of the knee joint model, but the magnitude of changes varied
      by an order of magnitude. CONCLUSIONS: The results suggest that (i) gait
      modification can benefit from considering whole-body motion rather than single
      adjustments, (ii) accurate interpretation of KAM effects on medial JCF requires
      consideration of muscle forces, and (iii) subject-specific knee models are needed
      to accurately determine the magnitude of KAM reduction effects on JCF.

PMID- 26215845
TI  - Treatment of infected nonunion total knee arthroplasty periprosthetic fracture
      using a stemmed articulating spacer.
AB  - BACKGROUND: We present a case of multifocal infection involving the left total
      hip replacement and the right total knee replacement of a patient, further
      complicated by an infected non-union of a periprosthetic fracture of the right
      knee. This required the unique simultaneous management of both infection
      eradication and fracture stabilization in the knee. METHODS: Both sites were
      treated with a two-stages procedure, including the novel use of a stemmed
      articulating spacer for the right knee. This spacer was made combining a
      retrograde humeral nail, coated with antibiotic-impregnated cement, and a pre
      formed articulating cement spacer. The patient was able to weight-bear on this
      spacer. RESULTS: The fracture went on to unite, and a second stage was performed
      with the use of stemmed prosthesis and augments. She remains infection free two
      years after the second stage operation. CONCLUSIONS: The use of a stemmed
      articulating knee spacer can facilitate infection eradication and fracture
      stabilization while preserving some motion and weight-bearing ability in the two
      stages management of an infected periprosthetic fracture of the knee. LEVEL OF
      EVIDENCE: Level V (Case report).

PMID- 26215846
TI  - Capsule Commentary on Bishu et al., Quantifying the Incremental and Aggregate
      Cost of Missed Workdays in Adults with Diabetes.

PMID- 26215848
TI  - Comment on the case report "bilateral atraumatic tibial tubercle avulsion
      fractures: case report and review of the literature" published in Injury, Int. J.
      Care Injured 46 (2015) 767-769.

PMID- 26215847
TI  - Variation among Primary Care Physicians in the Use of Imaging for Older Patients
      with Acute Low Back Pain.
AB  - BACKGROUND: Diagnostic imaging is not recommended in the evaluation and
      management of non-specific acute low back pain. OBJECTIVE: To estimate the
      variation among primary care providers (PCPs) in the use of diagnostic imaging
      for older patients with non-specific acute low back pain. DESIGN AND
      PARTICIPANTS: Retrospective cohort study using 100 % Texas Medicare claims data.
      We identified 145,320 patients aged 66 years and older with non-specific acute
      low back pain during the period January 1, 2007, through November 30, 2011, cared
      for by 3297 PCPs. MAIN MEASURES: We tracked whether each patient received lumbar
      imaging (radiography, computed tomography [CT], or magnetic resonance imaging
      [MRI]) within 4 weeks of the initial visit. Multilevel logistic regression models
      were used to estimate physician-level variation in imaging use. KEY RESULTS:
      Among patients, 27.2 % received radiography and 11.1 % received CT or MRI within
      4 weeks of the initial visit for low back pain. PCPs varied substantially in the
      use of imaging. The average rate of radiography within 4 weeks was 53.9 % for
      PCPs in the highest decile, compared to 6.1 % for PCPs in the lowest decile. The
      average rates of CT/MRI within 4 weeks were 18.5 % vs. 3.2 % for PCPs in the
      highest and lowest deciles, respectively. The specific physician seen by a
      patient accounted for 25 % of the variability in whether imaging was performed,
      while only 0.44 % of the variance was due to measured patient characteristics and
      1.4 % to known physician characteristics. Use of imaging by individual physicians
      was stable over time. CONCLUSIONS: PCPs vary substantially in the use of imaging
      for non-specific acute low back pain. Provider-level measures can be employed to
      provide feedback to physicians in an effort to modify imaging use.

PMID- 26215849
TI  - Characteristics of human primary mantle cell lymphoma engraftment in NSG mice.

PMID- 26215850
TI  - Ultrasonographic diagnosis of congenital membranous jejunal stenosis and gastric
      duplication cyst in a newborn: a case report.
AB  - INTRODUCTION: Congenital jejunal stenosis and gastric duplication cysts are very
      rare congenital anomalies of the gastrointestinal tract in the newborn. We
      present a case of congenital membranous jejunal stenosis associated with gastric
      duplication cysts, which was diagnosed by ultrasonography. To the best of our
      knowledge, this is the first report of ultrasonographic diagnosis of congenital
      membranous jejunal stenosis associated with a gastric duplication cyst in a
      newborn. CASE PRESENTATION: A 1-month-old Chinese baby girl presented with
      projectile vomiting and hyperpyrexia for 3 days. An upper gastrointestinal
      contrast study showed incomplete duodenal obstruction; however, ultrasonography
      revealed congenital membranous jejunal stenosis associated with a gastric
      duplication cyst. After surgical excision of the jejunal membrane and gastric
      duplication cyst, she recovered well with no bilious vomiting at the 1-year
      follow-up. CONCLUSION: Ultrasonography is a useful tool for the evaluation of
      membranous jejunal stenosis and the identification of small, asymptomatic
      gastrointestinal duplication cysts.

PMID- 26215851
TI  - Using multiple timescale models for the evaluation of a time-dependent treatment.
AB  - In survival analysis, the absolute measure of cumulative risk provided by the
      Kaplan-Meier estimator is still the most used quantity for its easy calculation
      and direct interpretability. However, for describing the survival after an
      intervention that may occur at different times from baseline observation, the
      Kaplan-Meier estimator generally yields to biased results if intervention is
      considered as fixed at baseline. The main focus of the present paper is to extend
      the use of a multiple timescale model in the presence of a time dependent
      intervention. The aim is to obtain 1) an estimate of treatment effect in terms of
      hazard ratios by flexible modeling, 2) a valid prediction tool, i.e. estimate of
      prognosis for a patient who changes treatment later in time, and 3) an
      appropriate graphical representation of survival in the presence of a time
      dependent treatment change, accounting for different timescales. We will show the
      advantages of this approach on the comparison of chemotherapy versus transplant
      in children with high-risk acute lymphoblastic leukemia in first remission. We
      considered a model with two timescales that accounts for the change in treatment
      at different times in the disease course. An alternative approach to survival
      estimates is also proposed which has some advantages over the traditional
      landmark approach: it uses all the data available to plot survival from the date
      of remission, it avoids the arbitrary choice of a landmark time and explicitly
      models the change in hazard due to transplant.

PMID- 26215853
TI  - Parental confidence in managing food allergy: development and validation of the
      Food Allergy Self-Efficacy Scale for Parents (FASE-P).
AB  - BACKGROUND: Food allergy is often a life-long condition that requires constant
      vigilance to prevent accidental exposure and avoid potentially life-threatening
      symptoms. Parents' confidence in managing their child's food allergy may relate
      to the poor quality of life anxiety and worry reported by parents of food
      allergic children. OBJECTIVE: The aim of this study was to develop and validate
      the first scale to measure parental confidence (self-efficacy) in managing food
      allergy in their child. METHODS: The Food Allergy Self-Efficacy Scale for Parents
      (FASE-P) was developed through interviews with 53 parents, consultation of the
      literature and experts in the area. The FASE-P was then completed by 434 parents
      of food-allergic children from a general population sample in addition to the
      General Self-Efficacy Scale (GSES), the Food Allergy Quality of Life Parental
      Burden Scale (FAQL-PB), the General Health Questionnaire-12 (GHQ-12) and the Food
      Allergy Impact Measure (FAIM). A total of 250 parents completed the retest of the
      FASE-P. RESULTS: Factor and reliability analysis resulted in a 21-item scale with
      five subscales. The overall scale and subscales have good to excellent internal
      consistency (Cronbach's alpha of 0.63-0.89), and the scale is stable over time.
      There were low to moderate significant correlations with the GSES, FAIM and GHQ
      12 and strong correlations with the FAQL-PB, with better parental confidence
      relating to better general self-efficacy, better quality of life and better
      mental health in the parent. Poorer self-efficacy was related to egg and milk
      allergy; self-efficacy was not related to severity of allergy. CONCLUSIONS AND
      CLINICAL RELEVANCE: The FASE-P is a reliable and valid scale for use with parents
      from a general population. Its application within clinical settings could aid
      provision of advice and improve targeted interventions by identifying areas where
      parents have less confidence in managing their child's food allergy.

PMID- 26215852
TI  - Improved diagnostics targeting c-MET in non-small cell lung cancer: expression,
      amplification and activation?
AB  - BACKGROUND: Several c-MET targeting inhibitory molecules have already shown
      promising results in the treatment of patients with Non-small Cell Lung Cancer
      (NSCLC). Combination of EGFR- and c-MET-specific molecules may overcome EGFR
      tyrosine kinase inhibitor (TKI) resistance. The aim of this study was to allow
      for the identification of patients who might benefit from TKI treatments
      targeting MET and to narrow in on the diagnostic assessment of MET. METHODS: 222
      tumor tissues of patients with NSCLC were analyzed concerning c-MET expression
      and activation in terms of phosphorylation (Y1234/1235 and Y1349) using a
      microarray format employing immunohistochemistry (IHC). Furthermore, protein
      expression and MET activation was correlated with the amplification status by
      Fluorescence in Situ Hybridization (FISH). RESULTS: Correlation was observed
      between phosphorylation of c-MET at Y1234/1235 and Y1349 (spearman correlation
      coefficient rs = 0.41; p < 0.0001). No significant correlation was shown between
      MET expression and phosphorylation (p > 0.05). c-MET gene amplification was
      detected in eight of 214 patients (3.7%). No significant association was observed
      between c-MET amplification, c-MET protein expression and phosphorylation.
      CONCLUSION: Our data indicate, that neither expression of c-MET nor the gene
      amplification status might be the best way to select patients for MET targeting
      therapies, since no correlation with the activation status of MET was observed.
      We propose to take into account analyzing the phosphorylation status of MET by
      IHC to select patients for MET targeting therapies. Signaling of the receptor and
      the activation of downstream molecules might be more crucial for the benefit of
      therapeutics targeting MET receptor tyrosine kinases than expression levels
      alone.

PMID- 26215854
TI  - Adoption of the 16-month American Board of Radiology pathway to dual board
      certifications in nuclear radiology and/or nuclear medicine for diagnostic
      radiology residents.

PMID- 26215855
TI  - An article to ADMIRE.

PMID- 26215856
TI  - Frontomaxillary facial angle in chromosomally normal Thai foetuses   at 11 to 13
      weeks 6 days '  gestation.
AB  - Frontomaxillary facial (FMF) angle is the angle between upper part of the
      anterior end of the maxillary bone and the line along the frontal bone in the
      midfacial profile view. Based on several previous studies, FMF angle can be
      useful in screening Down syndrome foetuses, in which FMF angle is significantly
      larger than that in euploid foetuses. However, racial factors can influence the
      FMF angle as seen in the different normal ranges among ethnicities. Therefore,
      before the clinical application of the FMF angle, a reference range for its own
      population should firstly be developed. In this study, a Thai reference range of
      FMF angle has been established. The mean FMF angle in euploid foetuses with a 60
      mm crown - rump length (CRL) was 81.07  degrees , with 0.23  degrees  increase
      for each mm increase in CRL, consistent with those observed in Caucasian and
      Chinese populations. The measurement of FMF angle has good reproducibility.

PMID- 26215857
TI  - D-dimer for the exclusion of cerebral venous thrombosis: a meta-analysis of low
      risk patients with isolated headache.
AB  - BACKGROUND: Patients with isolated headache may have cerebral venous thrombosis
      (CVT). D-dimers are proven sensitive in excluding deep venous thrombosis (DVT)
      and pulmonary embolism (PE) in low risk patients. We aimed to determine whether D
      dimer may play the same role in low risk CVT patients with isolated headache.
      METHODS: We included consecutive patients suspected of CVT from our teaching
      hospital with isolated headache, a normal neurological examination and normal
      standard head CT in whom D-dimer was determined. Additionally we did a systematic
      review on articles describing consecutive patients suspected of CVT with isolated
      headache and their D-dimer values. CVT was investigated with CT or MR venography
      in all patients. RESULTS: A total of 636 consecutive patients were collected from
      our own data and the literature search. Of 45 CVT patients one had a negative D
      dimer (7.5 %). Sensitivity of D-dimer for diagnosing CVT was 97.8 % (95 % CI:
      88.2-99.6 %), specificity was 84.9 % (95 % CI: 81.8-87.7 %), positive predictive
      value was 33.1 % (95 % CI: 25.2-41.7 %), negative predictive value was 99.8 % (95
      % CI: 98.9-100 %). Another 56 isolated headache CVT patients were identified in
      literature, lacking consecutive isolated headache controls. Sensitivity of D
      dimer for diagnosing CVT including these patients was 87.1 % (95 % CI: 79.0-93.0
      %). CONCLUSIONS: D-dimers have a high negative predictive value in patients with
      isolated headache for excluding CVT. Sensitivity is lower but comparable to the
      values accepted in PE and DVT. Low risk patients were defined as headache
      patients with a normal neurological examination, normal standard head CT and
      absence of risk factors such as pregnancy or puerperium. Normal D-dimers in these
      patients may reduce unnecessary imaging, making it a potential valuable marker.

PMID- 26215858
TI  - Introduction: Precision Medicine for Glomerular Disease: The Road Forward.

PMID- 26215859
TI  - Opportunities and Challenges of Genotyping Patients With Nephrotic Syndrome in
      the Genomic Era.
AB  - Both targeted and genome-wide linkage and association studies have identified a
      number of genes and genetic variants associated with nephrotic syndrome (NS).
      Genotype-phenotype studies of patients with these variants have identified
      correlations of clear clinical significance. Combined with improved genomic
      technologies, this has resulted in increasing, and justifiable, enthusiasm for
      incorporating our patients' genomic information into our clinical management
      decisions. Here, we summarize our understanding of NS-associated genetic factors,
      namely rare causal mutations or common risk alleles in apolipoprotein L1. We
      discuss the complexities inherent in trying to ascribe risk or causality to these
      variants, particularly as we seek to extend genetic testing to a broader group of
      patients, including many with sporadic disease. Overall, the thoughtful
      application and interpretation of these genetic tests will maximize the benefits
      to our patients with NS in the form of more precise clinical care. 

PMID- 26215860
TI  - APOL1 Kidney Disease Risk Variants: An Evolving Landscape.
AB  - Apolipoprotein L1 (APOL1) genetic variants account for much of the excess risk of
      chronic and end-stage kidney disease, which results in a significant global
      health disparity for persons of African ancestry. We estimate the lifetime risk
      of kidney disease in APOL1 dual-risk allele individuals to be at least 15%.
      Experimental evidence suggests a direct role of APOL1 in pore formation, cellular
      injury, and programmed cell death in renal injury. The APOL1 BH3 motif, often
      associated with cell death, is unlikely to play a role in APOL1-induced
      cytotoxicity because it is not conserved within the APOL family and is
      dispensable for cell death in vitro. We discuss two models for APOL1 trypanolytic
      activity: one involving lysosome permeabilization and another involving colloid
      osmotic swelling of the cell body, as well as their relevance to human
      pathophysiology. Experimental evidence from human cell culture models suggests
      that both mechanisms may be operative. A systems biology approach whereby APOL1
      associated perturbations in gene and protein expression in affected individuals
      are correlated with molecular pathways may be productive to elucidate APOL1
      function in vivo. 

PMID- 26215861
TI  - Genes Caught In Flagranti: Integrating Renal Transcriptional Profiles With
      Genotypes and Phenotypes.
AB  - In the past decade, population genetics has gained tremendous success in
      identifying genetic variations that are statistically relevant to renal diseases
      and kidney function. However, it is challenging to interpret the functional
      relevance of the genetic variations found by population genetics studies. In this
      review, we discuss studies that integrate multiple levels of data, especially
      transcriptome profiles and phenotype data, to assign functional roles of genetic
      variations involved in kidney function. Furthermore, we introduce state-of-the
      art machine learning algorithms, Bayesian networks, support vector machines, and
      Gaussian process regression, which have been applied successfully to integrating
      genetic, regulatory, and clinical information to predict clinical outcomes. These
      methods are likely to be deployed successfully in the nephrology field in the
      near future. 

PMID- 26215863
TI  - Matching Kidneys and Urines: Establishing Noninvasive Surrogates of Intrarenal
      Events in Primary Glomerulonephritis.
AB  - Kidney biopsy is the gold standard procedure for providing diagnostic and
      prognostic information for patients with glomerular-based diseases, however, the
      utility of this procedure for assessing longitudinal disease activity is limited.
      The intense search for noninvasive biomarkers of kidney disease activity and
      injury is driven in large part by the inherent risks of the kidney biopsy
      procedure and limited information derived from the morphologic description of
      biopsy findings. Furthermore, gaps in our understanding of the core intrarenal
      molecular processes underlying the development and progression of glomerular
      based diseases has limited the development of effective targeted therapy. In this
      review, we discuss the potential utility of molecular analysis of the urine to
      provide a dynamic window into intrarenal molecular and morphologic responses. We
      focus on molecular analysis of the urine to identify noninvasive surrogate
      markers of kidney responses, with the goal of using these biomarkers as more
      sensitive indicators of progression and tissue-level responses to therapeutic
      interventions in patients with primary glomerulonephritis. 

PMID- 26215862
TI  - Podometrics as a Potential Clinical Tool for Glomerular Disease Management.
AB  - Chronic kidney disease culminating in end-stage kidney disease is a major public
      health problem costing in excess of $40 billion per year with high morbidity and
      mortality. Current tools for glomerular disease monitoring lack precision and
      contribute to poor outcome. The podocyte depletion hypothesis describes the major
      mechanisms underlying the progression of glomerular diseases, which are
      responsible for more than 80% of cases of end-stage kidney disease. The question
      arises of whether this new knowledge can be used to improve outcomes and reduce
      costs. Podocytes have unique characteristics that make them an attractive
      monitoring tool. Methodologies for estimating podocyte number, size, density,
      glomerular volume and other parameters in routine kidney biopsies, and the rate
      of podocyte detachment from glomeruli into urine (podometrics) now have been
      developed and validated. They potentially fill important gaps in the glomerular
      disease monitoring toolbox. The application of these tools to glomerular disease
      groups shows good correlation with outcome, although data validating their use
      for individual decision making is not yet available. Given the urgency of the
      clinical problem, we argue that the time has come to focus on testing these tools
      for application to individualized clinical decision making toward more effective
      progression prevention. 

PMID- 26215865
TI  - Matching the Genotype in Resolution: Innovative Ways of Phenotype Capture.
AB  - Social and spatial context are important determinants of morbidity and mortality.
      However, there is little clarity about the role of context for kidney disease
      specifically, particularly before the end stage. Meanwhile, research clarifying
      the clinical, cellular, molecular, and genetic causes of kidney disease is
      accelerating considerably. We postulate that without contextual information, even
      the most detailed biomedical information cannot fully capture the factors that
      ultimately drive the development and progression of kidney disease. The Nephrotic
      Syndrome Study Network is integrating detailed, state-of-the-art information on a
      social and spatial context to enable the exploration of the associations between
      the social environment and kidney disease. Here, we discuss the extant literature
      on social context and kidney disease, present information on sources of
      contextual information, and provide recommended further reading to facilitate
      future research on the contribution of the social context to kidney disease. 

PMID- 26215864
TI  - Morphology in the Digital Age: Integrating High-Resolution Description of
      Structural Alterations With Phenotypes and Genotypes.
AB  - Conventional light microscopy has been used to characterize and classify renal
      diseases, evaluate histopathology in studies and trials, and educate renal
      pathologists and nephrologists. The advent of digital pathology, in which a glass
      slide can be scanned to create whole slide images (WSIs) for viewing and
      manipulating on a computer monitor, provides real and potential advantages
      compared with conventional light microscopy. Software tools such as annotation,
      morphometry, and image analysis can be applied to WSIs for studies or educational
      purposes, and the digital images are available globally to clinicians,
      pathologists, and investigators. New ways of assessing renal pathology with
      observational data collection may allow better morphologic correlations and
      integration with molecular and genetic signatures, refinements of classification
      schema, and understanding of disease pathogenesis. In multicenter studies, WSIs,
      which require additional quality assurance steps, provide efficiency by reducing
      slide shipping and consensus conference costs, and they allow slide viewing
      anytime and anywhere. Although validation studies for the routine diagnostic use
      of digital pathology still are needed, this is a powerful tool currently
      available for translational research, clinical trials, and education in renal
      pathology. 

PMID- 26215866
TI  - Research Infrastructure for Collaborative Team Science: Challenges in Technology
      Supported Workflows in and Across Laboratories, Institutions, and Geographies.
AB  - Collaborative research has many challenges. One under-researched challenge is how
      to align collaborators' research practices and evolving analytical reasoning with
      technologies and configurations of technologies that best support them. The goal
      of such alignment is to enhance collaborative problem solving capabilities in
      research. Toward this end, we draw on our own research and a synthesis of the
      literature to characterize the workflow of collaborating scientists in systems
      level renal disease research. We describe the various phases of a hypothetical
      workflow among diverse collaborators within and across laboratories, extending
      from their primary analysis through secondary analysis. For each phase, we
      highlight required technology supports, and. At time, complementary
      organizational supports. This survey of supports matching collaborators' analysis
      practices and needs in research projects to technological support is preliminary,
      aimed ultimately at developing a research capability framework that can help
      scientists and technologists mutually understand workflows and technologies that
      can help enable and enhance them. 

PMID- 26215867
TI  - Do body mass index trajectories affect the risk of type 2 diabetes? A case
      control study.
AB  - BACKGROUND: Although obesity is a well-studied risk factor for diabetes, there
      remains an interest in whether "increasing body mass index (BMI)," "high BMI per
      se," or both are the actual risk factors for diabetes. The present study aimed to
      retrospectively compare BMI trajectories of individuals with and without diabetes
      in a case-control design and to assess whether increasing BMI alone would be a
      risk factor. METHODS: Using comprehensive health check-up data measured over ten
      years, we conducted a case-control study and graphically drew the trajectories of
      BMIs among diabetic patients and healthy subjects, based on coefficients in
      fitted linear mixed-effects models. Patient group was matched with healthy
      control group at the onset of diabetes with an optimal matching method in a 1:10
      ratio. Simple fixed-effects models assessed the differences in increasing BMIs
      over 10 years between patient and control groups. RESULTS: At the time of
      matching, the mean ages in male patients and controls were 59.3 years [standard
      deviation (SD) = 9.2] and 57.7 years (SD = 11.2), whereas the mean BMIs were 25.0
      kg/m(2) (SD = 3.1) and 25.2 kg/m(2) (SD = 2.9), respectively. In female patients
      and controls, the mean ages were 61.4 years (SD = 7.9) and 60.1 years (SD = 9.6),
      whereas the mean BMIs were 24.8 kg/m(2) (SD = 3.5) and 24.9 kg/m(2) (SD = 3.4),
      respectively. The simple fixed-effects models detected no statistical
      significance for the differences of increasing BMIs between patient and control
      groups in males (P = 0.19) and females (P = 0.67). Sudden increases in BMI were
      observed in both male and female patients when compared with BMIs 1 year prior to
      diabetes onset. CONCLUSIONS: The present study suggested that the pace of
      increasing BMIs is similar between Japanese diabetic patients and healthy
      individuals. The increasing BMI was not detected to independently affect the
      onset of type 2 diabetes.

PMID- 26215868
TI  - A TPL2 (MAP3K8) disease-risk polymorphism increases TPL2 expression thereby
      leading to increased pattern recognition receptor-initiated caspase-1 and caspase
      8 activation, signalling and cytokine secretion.
AB  - OBJECTIVE: IBD is characterised by dysregulated intestinal immune homeostasis and
      cytokine secretion. In the intestine, properly regulating pattern recognition
      receptor (PRR)-mediated signalling and cytokines is crucial given the ongoing
      host-microbial interactions. TPL2 (MAP3K8, COT) contributes to PRR-initiated
      pathways, yet the mechanisms for TPL2 signalling contributions in primary human
      myeloid cells are incompletely understood and its role in intestinal myeloid
      cells is poorly defined. Furthermore, functional consequences for the IBD-risk
      locus rs1042058 in TPL2 are unknown. METHODS: We analysed protein, cytokine and
      RNA expression, and signalling in human monocyte-derived macrophages (MDMs)
      through western blot, ELISA, real-time PCR and flow cytometry. RESULTS: PRR
      induced cytokine secretion was increased in MDMs from rs1042058 TPL2 GG risk
      individuals. TPL2 activation by the Crohn's disease-associated PRR nucleotide
      oligomerisation domain (NOD)2 required PKC, and IKKbeta, IKKalpha and IKKgamma
      signalling. TPL2, in turn, significantly enhanced NOD2-induced ERK, JNK and
      NFkappaB signalling. We found that another major mechanism for the TPL2
      contribution to NOD2 signalling was through ERK-dependent and JNK-dependent
      caspase-1 and caspase-8 activation, which in turn, led to early autocrine
      interleukin (IL)-1beta and IL-18 secretion and amplification of long-term
      cytokines. Importantly, Salmonella typhimurium-induced cytokines from human
      intestinal myeloid-derived cells required TPL2 as well as autocrine IL-1beta and
      IL-18. Finally, rs1042058 GG risk carrier MDMs from healthy individuals and
      patients with Crohn's disease had increased TPL2 expression and NOD2-initiated
      TPL2 phosphorylation, ERK, JNK and NFkappaB activation, and early autocrine IL
      1beta and IL-18 secretion. CONCLUSIONS: Taken together, the rs1042058 GG IBD-risk
      polymorphism in TPL2 results in a gain-of-function by increasing TPL2 expression
      and signalling, thereby amplifying PRR-initiated outcomes.

PMID- 26215869
TI  - Water-soluble lipophilic MR contrast agents for cell membrane labeling.
AB  - Long-term cell tracking using MR imaging necessitates the development of contrast
      agents that both label and are retained by cells. One promising strategy for long
      term cell labeling is the development of lipophilic Gd(III)-based contrast agents
      that anchor into the cell membrane. We have previously reported the efficacy of
      monomeric and multimeric lipophilic agents and showed that the monomeric agents
      have improved labeling and contrast enhancement of cell populations. Here, we
      report on the synthesis, characterization, and in vitro testing of a series of
      monomeric lipophilic contrast agents with varied alkyl chain compositions. We
      show that these agents disperse in water, localize to the cell membrane, and
      label HeLa and MCF7 cells effectively. Additionally, these agents have up to
      tenfold improved retention in cells compared to clinically available
      ProHance((r)). 

PMID- 26215870
TI  - Lipoprotein heterogeneity in persons with Spinal Cord Injury: a model of
      prolonged sitting and restricted physical activity.
AB  - BACKGROUND: Persons with spinal cord injury (SCI) often have low levels of
      physical activity, which predispose to increased adiposity and decreased high
      density lipoprotein cholesterol (HDL-C) concentrations, and, generally, normal
      low density lipoprotein cholesterol (LDL-C) concentrations. In spite of the mixed
      lipoprotein profile, the SCI population has been reported to have an elevated
      risk of cardiovascular-related morbidity and mortality. Nuclear magnetic
      resonance spectroscopy may permit a more precise quantification of lipoprotein
      particle (P) species, enabling a more accurate inference of risk for
      cardiovascular disease (CVD) in the SCI population. METHODS: Fasting blood
      samples were obtained on 83 persons with chronic SCI and 62 able-bodied (AB)
      subjects. Fasting plasma insulin (FPI), triglycerides (TG), and P number and size
      of VLDL (very low density lipoprotein), LDL, and HDL subclasses were determined.
      AB and SCI subjects were stratified based on HDL-C (i.e., Low <40 and Normal >=
      40 mg/dl): AB-Normal (n = 48), AB-Low (n = 14), SCI-Normal (n = 49), and SCI-Low
      (n = 34). Factorial analyses of variance were performed to identify group
      differences in lipoprotein measurements. Pearson correlations were performed
      between the number of P by lipoprotein subclass, size, FPI, and TG. RESULTS: The
      SCI-Normal group was not significantly different from the AB-Normal group for
      body composition, FPI, TG or LP-IR and had negligible differences in the
      lipoprotein P profile, except for fewer number and smaller size of HDL-P. The SCI
      Low group had a similar lipoprotein profile to that of the AB-Low group, but with
      a lipid P composition associated with a heightened atherogenic risk and greater
      tendency toward insulin resistance by the Lipoprotein-Insulin Resistance (LP-IR)
      score. In the SCI-Low group, the decreased number and reduced size of lipoprotein
      P were more prevalent and may be associated with increased waist circumference
      (i.e., abdominal adiposity), relatively elevated TG values (compared to the other
      subgroups), and an underlying subclinical state of insulin resistance.
      CONCLUSIONS: Prolonged sitting and restricted physical activity in individuals
      with SCI had the most profound effect on the HDL-C and its lipoprotein P
      subclasses, but not on LDL-C, however its P subclasses were also unfavorably
      affected but not to the same degree. The quantification of lipoprotein P
      characteristics may be a potent tool for the determination of risk for CVD in
      persons with SCI.

PMID- 26215872
TI  - [Foot drop following spinal anaesthesia].

PMID- 26215871
TI  - Cost-effectiveness analysis of dabigatran and anticoagulation monitoring
      strategies of vitamin K antagonist.
AB  - BACKGROUND: Vitamin K antagonists are commonly used for the prevention of
      thromboembolic events. Patient self-monitoring of vitamin K antagonists has
      proved superior to usual care. Dabigatran has been shown, relative to warfarin,
      to reduce thromboembolic events without increasing bleeding. METHODS: We
      constructed a Markov model to compare vitamin K self-monitoring strategies to
      dabigatran including effectiveness and costs of monitoring and complications
      (thromboembolism and major bleeding). The model was used to project the incidence
      of these complications, life years, quality-adjusted life years, and health
      system costs with anticoagulant treatment throughout life. The analysis was
      conducted from the health system perspective and from the societal perspective.
      RESULTS: Low quality evidence suggests that self-monitoring is at least as
      effective as dabigatran for the outcomes of thrombosis, bleeding and death.
      Moderate quality evidence that patient self-monitoring is more effective than
      other forms of monitoring degree of anticoagulation with vitamin K antagonists,
      reducing the relative risk of thromboembolism by 41% and death by 34%. The cost
      per quality adjusted year gained relative to other warfarin monitoring strategies
      is well below 30,000 ? in the short term, and is a dominant alternative from the
      fourth year. In comparison with dabigatran, the lower annual cost and its
      equivalence in terms of effectiveness made self-monitoring the dominant option.
      These results were confirmed in the probabilistic sensitivity analysis.
      CONCLUSIONS: We have moderate quality evidence that self-monitoring of vitamin K
      antagonists is a cost-effective alternative compared with hospital and primary
      care monitoring, and low quality evidence, compared with dabigatran. Our analyses
      contrast with the available cost analysis of dabigatran and usual care of
      anticoagulated patients.

PMID- 26215873
TI  - Penetration depth of corneal cross-linking with riboflavin and UV-A (CXL) in
      horses and rabbits.
AB  - OBJECTIVE: CXL penetration depth is an important variable influencing clinical
      treatment effect and safety. The purposes of this study were to determine the
      penetration depth of CXL in rabbit and equine corneas in epithelium-on and
      epithelium-off procedures and to assess an ex vivo fluorescent biomarker staining
      assay for objective assessment of CXL penetration depth. PROCEDURES: CXL
      treatment was performed according to a standardized protocol on 21 and 17 rabbit
      eyes and on 12 and 10 equine eyes with and without debridement, respectively.
      Control corneas were treated similarly, but not exposed to CXL. Hemicorneas were
      stained with either phalloidin and DAPI to visualize intracellular F-actin and
      nuclei, or with hematoxylin and eosin. Loss of actin staining was measured and
      compared between groups. RESULTS: Epithelium-off CXL caused a median actin
      cytoskeleton loss with a demarcation at 274 MUm in rabbits and 173 MUm in horses.
      In non-CXL-treated controls, we observed a median actin cytoskeleton loss with a
      demarcation at 134 MUm in rabbits and 149 MUm in horses. No effect was detected
      in the epithelium-on procedure. CONCLUSIONS: CXL penetration depth, as determined
      by a novel ex vivo fluorescent assay, shows clear differences between species. A
      distinct effect was observed following epithelium-off CXL treatment in the
      anterior stroma of rabbits, but no different effect was observed in horses in
      comparison with nontreated controls. Different protocols need to be established
      to effectively treat equine patients with infectious corneal disease.

PMID- 26215874
TI  - Protein prenylation in islet beta-cell function in health and diabetes: Putting
      the pieces of the puzzle together.
AB  - Post-translational prenylation involves incorporation of 15-(farnesyl) or 20
      (geranylgeranyl) carbon derivatives of mevalonic acid into highly conserved C
      terminal cysteines of proteins. The farnesyl transferase (FTase) and the
      geranylgeranyl transferase (GGTase) mediate incorporation of farnesyl and
      geranylgeranyl groups, respectively. At least 300 proteins are prenylated in the
      human genome; the majority of these are implicated in cellular processes
      including growth, differentiation, cytoskeletal function and vesicle trafficking.
      From a functional standpoint, isoprenylation is requisite for targeting of
      modified proteins to relevant cellular compartments for regulation of effector
      proteins. Pharmacological and molecular biological studies have provided
      compelling evidence for key roles of this signaling pathway in physiological
      insulin secretion in normal rodent and human islets. Recent evidence indicates
      that inhibition of prenylation results in mislocalization of unprenylated
      proteins, and surprisingly, they remain in active (GTP-bound) conformation.
      Sustained activation of G proteins has been reported in mice lacking GGTase,
      suggesting alternate mechanisms for the activation of non-prenylated G proteins.
      These findings further raise an interesting question if mislocalized, non
      prenylated and functionally active G proteins cause cellular pathology since
      aberrant protein prenylation has been implicated in the onset of cardiovascular
      disease and diabetes. Herein, we overview the existing evidence to implicate
      prenylation in islet function and potential defects in this signaling pathways in
      the diabetic beta-cell. We will also identify critical knowledge gaps that need
      to be addressed for the development of therapeutics to halt defects in these
      signaling steps in beta cells in models of impaired insulin secretion, metabolic
      stress and diabetes. 

PMID- 26215875
TI  - AChR-specific immunosuppressive therapy of myasthenia gravis.
AB  - Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by
      muscle fatigability. In most cases, it is mediated by autoantibodies targeting
      muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction.
      Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which
      is usually induced by immunization with AChR purified from fish electric organ.
      Pathological autoantibodies to AChRs are directed at the extracellular surface,
      especially the main immunogenic region (MIR). Current treatments for MG can help
      many but not all patients. Antigen-specific immunosuppressive therapy for MG that
      specifically suppresses the autoimmune response without affecting the entire
      immune system and avoids side effects of general immunosuppression is currently
      unavailable. Early attempts at antigen-specific immunosuppression for EAMG using
      AChR extracellular domain sequences that form epitopes for pathological
      autoantibodies risked provoking autoimmunity rather than suppressing it. We
      discovered a novel approach to specific immunosuppression of EAMG with a
      therapeutic vaccine consisting of bacterially-expressed human AChR cytoplasmic
      domains, which has the potential to specifically suppress MG without danger of
      causing exacerbation. This approach prevents development of chronic EAMG when
      initiated immediately after the acute phase of EAMG, and rapidly reverses
      established chronic EAMG when started during the chronic phase of EAMG.
      Successfully treated rats exhibited long-term resistance to re-induction of EAMG.
      In this review we also discuss the current understanding of the mechanisms by
      which the therapy works. Vaccination with AChR cytoplasmic domains in adjuvant is
      promising as a safe, antigen-specific, potent, effective, rapidly acting, and
      long lasting approach to therapy of MG. 

PMID- 26215876
TI  - Relationship between inflammatory cytokines and risk of depression, and effect of
      depression on the prognosis of high grade glioma patients.
AB  - Depression is found to be associated with up-regulation of inflammatory
      cytokines. However, the relationship in high grade glioma (HGG) patients is still
      unclear. In this prospective study, a total 132 HGG patients participated in
      blood sample collection for inflammatory cytokines detection by ELISA, mental
      status, quality of life (QOL) and physical functional status testing. The
      association between inflammatory cytokines and depression risk was assessed using
      conditional logistic regression. The incidences of depressive symptoms and
      depression in high grade glioama patients were 45.5 and 25 % respectively during
      12 months follow-up. We found the risk of depression was elevated with increased
      C-reactive protein (CRP) and interleukin-6 (IL-6) in high grade glioma patients
      after adjustment of confounders. The serum levels of CRP and IL-6 in patients
      with transient depression and depression were higher than those without
      depressive symptoms. In addition, depression had significant effects on the
      survival, QOL and physical functional status of patients. Depression is prevalent
      among patients with HGG. The present study suggests that serum CRP and IL-6 may
      serve as a depression marker for HGG patients. The survival and quality of life
      of HGG patients may be improved by an effective management for depression. 

PMID- 26215878
TI  - Pseudo-Foster-Kennedy syndrome with optic nerve compression by the gyrus rectus.

PMID- 26215877
TI  - Evidence-based guideline summary: Evaluation, diagnosis, and management of
      facioscapulohumeral muscular dystrophy: Report of the Guideline Development,
      Dissemination, and Implementation Subcommittee of the American Academy of
      Neurology and the Practice Issues Review Panel of the American Association of
      Neuromuscular & Electrodiagnostic Medicine.
AB  - OBJECTIVE: To develop recommendations for the evaluation, diagnosis,
      prognostication, and treatment of facioscapulohumeral muscular dystrophy (FSHD)
      from a systematic review and analysis of the evidence. METHODS: Relevant articles
      were analyzed in accordance with the American Academy of Neurology classification
      of evidence schemes for diagnostic, prognostic, and treatment studies.
      Recommendations were linked to the strength of the evidence and other factors.
      RESULTS AND RECOMMENDATIONS: Available genetic testing for FSHD type 1 is highly
      sensitive and specific. Although respiratory insufficiency occurs rarely in FSHD,
      patients with severe FSHD should have routine pulmonary function testing. Routine
      cardiac screening is not necessary in patients with FSHD without cardiac
      symptoms. Symptomatic retinal vascular disease is very rare in FSHD. Exudative
      retinopathy, however, is potentially preventable, and patients with large
      deletions should be screened through dilated indirect ophthalmoscopy. The
      prevalence of clinically relevant hearing loss is not clear. In clinical
      practice, patients with childhood-onset FSHD may have significant hearing loss.
      Because undetected hearing loss may impair language development, screening
      through audiometry is recommended for such patients. Musculoskeletal pain is
      common in FSHD and treating physicians should routinely inquire about pain. There
      is at present no effective pharmacologic intervention in FSHD. Available studies
      suggest that scapular fixation is safe and effective. Surgical scapular fixation
      might be cautiously offered to selected patients. Aerobic exercise in FSHD
      appears to be safe and potentially beneficial. On the basis of the evidence,
      patients with FSHD might be encouraged to engage in low-intensity aerobic
      exercises.

PMID- 26215879
TI  - Drawing in Alzheimer-type dementia.

PMID- 26215880
TI  - Author response.

PMID- 26215881
TI  - Motoric cognitive risk syndrome: multicenter incidence study.

PMID- 26215882
TI  - Mystery case: A case of oil in ventricles: deception for intraventricular
      hemorrhage.

PMID- 26215883
TI  - Clinical Reasoning: a 51-year-old woman with weakness and stiff neck.

PMID- 26215884
TI  - Child Neurology: medium-chain acyl-coenzyme A dehydrogenase deficiency.

PMID- 26215885
TI  - Diagnosis and treatment of facioscapulohumeral muscular dystrophy: 2015
      guidelines.

PMID- 26215886
TI  - Assisted mechanical ventilation: the future is now!
AB  - Assisted ventilation is a highly complex process that requires an intimate
      interaction between the ventilator and the patient. The complexity of this form
      of ventilation is frequently underappreciated by the bedside clinician. In
      assisted mechanical ventilation, regardless of the specific mode, the
      ventilator's gas delivery pattern and the patient's breathing pattern must match
      near perfectly or asynchrony between the patient and the ventilator occurs.
      Asynchrony can be categorized into four general types: flow asynchrony; trigger
      asynchrony; cycle asynchrony; and mode asynchrony. In an article recently
      published in BMC Anesthesiology, Hodane et al. have demonstrated reduced
      asynchrony during assisted ventilation with Neurally Adjusted Ventilatory Assist
      (NAVA) as compared to pressure support ventilation (PSV). These findings add to
      the growing volume of data indicating that modes of ventilation that provide
      proportional assistance to ventilation - e.g., NAVA and Proportional Assist
      Ventilation (PAV) - markedly reduce asynchrony. As it becomes more accepted that
      the respiratory center of the patient in most circumstances is the most
      appropriate determinant of ventilatory pattern and as the negative outcome
      effects of patient-ventilator asynchrony become ever more recognized, we can
      expect NAVA and PAV to become the preferred modes of assisted ventilation! 

PMID- 26215887
TI  - Potentiometric detection of chemical vapors using molecularly imprinted polymers
      as receptors.
AB  - Ion-selective electrode (ISE) based potentiometric gas sensors have shown to be
      promising analytical tools for detection of chemical vapors. However, such
      sensors are only capable of detecting those vapors which can be converted into
      ionic species in solution. This paper describes for the first time a polymer
      membrane ISE based potentiometric sensing system for sensitive and selective
      determination of neutral vapors in the gas phase. A molecularly imprinted polymer
      (MIP) is incorporated into the ISE membrane and used as the receptor for
      selective adsorption of the analyte vapor from the gas phase into the sensing
      membrane phase. An indicator ion with a structure similar to that of the vapor
      molecule is employed to indicate the change in the MIP binding sites in the
      membrane induced by the molecular recognition of the vapor. The toluene vapor is
      used as a model and benzoic acid is chosen as its indicator. Coupled to an
      apparatus manifold for preparation of vapor samples, the proposed ISE can be
      utilized to determine volatile toluene in the gas phase and allows potentiometric
      detection down to parts per million levels. This work demonstrates the
      possibility of developing a general sensing principle for detection of neutral
      vapors using ISEs. 

PMID- 26215888
TI  - Evaluating cost and resource use associated with pulse oximetry screening for
      critical congenital heart disease: Empiric estimates and sources of variation.
AB  - BACKGROUND: Newborn screening for critical congenital heart disease (CCHD) using
      pulse oximetry is being implemented in the United States and internationally;
      however, few data are available on the associated in-hospital costs and use of
      resources. METHODS: Time and motion study in well-baby nurseries at two large
      urban hospitals in Utah using different approaches to pulse oximetry screening.
      Two observers recorded the time for each screening step together with provider
      and equipment characteristics. Structured questionnaire provided additional
      information on labor and equipment costs. RESULTS: Fifty-three CCHD screens were
      observed. At site A (n = 22), screening was mostly done by medical assistants
      (95%) using disposable probes (100%); at site B (n = 31), screening was mostly
      performed by certified nursing assistants (90%) using reusable probes (90%).
      Considering only first screens (n = 53), the median screen time was 8.6 min
      (range: 3.2-23.2), with no significant difference between sites. The overall cost
      ($ in 2014) of screening per baby was $24.52 at site A and $2.60 at site B.
      Nearly all the variation in cost (90%) was due to the cost of disposable probes;
      labor costs were similar between sites. CONCLUSION: CCHD screening by means of
      pulse oximetry is reasonably fast for most babies, leading to relative small
      labor costs with little variation by provider type. The main driver of costs is
      equipment: in a high throughput setting, reusable probes are currently associated
      with considerable cost saving compared with disposable probes. As programs expand
      to universal screening, improved and cheaper technologies could lead to
      considerable economies of scale.

PMID- 26215890
TI  - [Idiopathic intracranial hypertension: pathogenesis, symptoms, diagnosis and
      therapy - an update].

PMID- 26215889
TI  - Serological signature of tick-borne pathogens in Scandinavian brown bears over
      two decades.
AB  - BACKGROUND: Anthropogenic disturbances are changing the geographic distribution
      of ticks and tick-borne diseases. Over the last few decades, the tick Ixodes
      ricinus has expanded its range and abundance considerably in northern Europe.
      Concurrently, the incidence of tick-borne diseases, such as Lyme borreliosis and
      tick-borne encephalitis, has increased in the human populations of the
      Scandinavian countries. METHODS: Wildlife populations can serve as sentinels for
      changes in the distribution of tick-borne diseases. We used serum samples from a
      long-term study on the Scandinavian brown bear, Ursus arctos, and standard
      immunological methods to test whether exposure to Borrelia burgdorferi sensu
      lato, the causative agent of Lyme borreliosis, and tick-borne encephalitis virus
      (TBEV) had increased over time. Bears had been sampled over a period of 18 years
      (1995-2012) from a southern area, where Ixodes ricinus ticks are present, and a
      northern area where ticks are uncommon or absent. RESULTS: Bears had high levels
      of IgG antibodies against B. burgdorferi sensu lato but not TBEV. Bears at the
      southern area had higher values of anti-Borrelia IgG antibodies than bears at the
      northern area. Over the duration of the study, the value of anti-Borrelia IgG
      antibodies increased in the southern area but not the northern area. Anti
      Borrelia IgG antibodies increased with the age of the bear but declined in the
      oldest age classes. CONCLUSIONS: Our study is consistent with the view that ticks
      and tick-borne pathogens are expanding their abundance and prevalence in
      Scandinavia. Long-term serological monitoring of large mammals can provide
      insight into how anthropogenic disturbances are changing the distribution of
      ticks and tick-borne diseases.

PMID- 26215891
TI  - Prognostic significance of platelet-derived growth factor receptor-beta
      expression in localized clear cell renal cell carcinoma.
AB  - PURPOSE: We investigated the expression status of vascular endothelial growth
      factor (VEGF), platelet-derived growth factor (PDGF)-B and their receptors in
      organ-confined clear cell renal cell carcinoma (ccRCC) to evaluate their
      prognostic significance after radical surgery. METHODS: In 758 consecutive
      patients diagnosed with pT1-2N0 ccRCC between 2007 and 2012, we prospectively
      investigated the expression levels of VEGF, PDGF-B, VEGF receptor (VEGFR) and
      PDGF receptor (PDGFR)-beta via immunohistochemistry. Clinicopathologic parameters
      and expression of the angiogenic factors were analyzed with respect to recurrence
      free survival (RFS) after nephrectomy. The median follow-up was 29.5 months (IQR
      21.5, 39.6) after surgery. RESULTS: Partial nephrectomy had been performed in
      48.5 % of the patients, and tumors were staged as pT1a in 514 (67.8 %), pT1b in
      192 (25.3 %) and pT2 in 52 (6.9 %). VEGF, PDGF and their receptors were
      identified in the cytoplasm and membranes of the tumor cells. Expression level of
      VEGFR inversely correlated with both tumor size (r = -0.076, p = 0.014) and
      nuclear grade (r = -0.297, p = 0.004). As for PDGF-B, the expression level showed
      an inverse correlation with tumor size (r = -0.216, p < 0.001) while PDGFR-beta
      inversely correlated with nuclear grade (r = -0.341, p = 0.001). On multivariate
      analysis, age, pathologic stage, nuclear grade and PDGFR-beta expression (high
      vs. low or none, HR 3.121 95 % CI 1.300-7.493, p = 0.011) were independently
      prognostic of RFS after nephrectomy. CONCLUSIONS: In organ-confined ccRCC, high
      expression of PDGFR-beta was independently predictive of poorer RFS after
      nephrectomy.

PMID- 26215892
TI  - Primary adrenal leiomyosarcoma treated by laparoscopic adrenalectomy.

PMID- 26215893
TI  - "When everything changes:" Parent perspectives on the challenges of accessing
      care for a child with a disability.
AB  - BACKGROUND: Health disparities exist among individuals living in rural and urban
      contexts in terms of access to health care and overall mortality. These
      disparities are typically greater for youth with disabilities living in rural
      areas, who face additional barriers in receiving health and support services
      specific to their disability. Parents are typically the ones responsible for
      coordinating the care needed by children with a disability; however, with
      numerous barriers present families are not provided adequate support to care for
      a child with disabilities. OBJECTIVE: The purpose of this study was to examine
      barriers and facilitators to accessing health and support services among urban
      and rural families of children with disabilities. METHODS: In-depth interviews
      were conducted with parents who provide care for an adolescent with a disability.
      The sample was comprised of parents from one rural county (N = 9) and one urban
      county (N = 10) in Georgia. Parental interviews were conducted face to face by a
      trained researcher. Each interview was audio-recorded. The recordings were
      transcribed and content analysis used to create codes and identify emerging
      themes. RESULTS: The common themes found during the analysis include
      accessibility of health and support resources, transitions, and social isolation.
      CONCLUSIONS: When comparing urban and rural areas, barriers to access do differ
      in terms of availability, but analysis revealed more similarities existed among
      parents from both contexts. Efforts must be made to increase opportunities for
      youth with disabilities to become connected with the local community in order to
      improve quality of life for families.

PMID- 26215894
TI  - [Managing a health research institute: towards research excellence through
      continuous improvement].
AB  - Health research institutes are a strategic commitment considered the ideal
      environment to develop excellence in translational research. Achieving quality
      research requires not only a powerful scientific and research structure but also
      the quality and integrity of management systems that support it. The essential
      instruments in our institution were solid strategic planning integrated into and
      consistent with the system of quality management, systematic evaluation through
      periodic indicators, measurement of key user satisfaction and internal audits,
      and implementation of an innovative information management tool. The implemented
      management tools have provided a strategic thrust to our institute while ensuring
      a level of quality and efficiency in the development and management of research
      that allows progress towards excellence in biomedical research. 

PMID- 26215895
TI  - Parental factors affecting the circumcision of non-Muslim Chinese boys include
      education and family history.
AB  - AIM: This study investigated the prevalence of circumcision among non-Muslim
      schoolboys in Urumqi, China, and how acceptable their parents found the practice.
      METHODS: A convenient cluster sample of non-Muslim schoolboys (n = 3614) aged six
      to 15 years of age and 873 mothers and 927 fathers completed self-administered
      questionnaires. We compared the consistency of the circumcision status reported
      by students and their parents and analysed the factors that influenced the
      parents to have their child circumcised. RESULTS: The mean age at circumcision
      was 8.3 years and the adjusted prevalence was 46.2%. Up to 45.4% of fathers and
      66% of mothers with uncircumcised sons were willing to circumcise their sons
      after receiving further information on circumcision. Mothers were more likely to
      support circumcision if they had higher education levels and higher family
      income, were employed as government officials and had family members who had been
      circumcised, including their husband. Fathers were more likely to support
      circumcision if they were highly educated and had been circumcised themselves.
      CONCLUSION: The prevalence and acceptability of circumcision were higher than
      expected in this traditional schoolboy population in Urumqi, China. Factors that
      increased parental support for circumcision included high education and the
      father being circumcised.

PMID- 26215896
TI  - The perspective of children on factors influencing their participation in
      perioperative care.
AB  - AIMS AND OBJECTIVES: To describe the experiences of participation in
      perioperative care of 8- to 11-year-old children. BACKGROUND: All children have
      the right to participate in decisions that affect them and have the right to
      express their views in all matters that concern them. Allowing children to be
      involved in their perioperative care can make a major difference in terms of
      their well-being by decreasing fear and anxiety and having more positive
      experiences. Taking the views of children into account and facilitating their
      participation could thus increase the quality of care. DESIGN: Descriptive
      qualitative design. METHODS: The study was conducted in 2013 and data were
      collected by narrative interviews with 10 children with experience from
      perioperative care in Sweden. Qualitative content analysis was chosen to describe
      the variations, differences and similarities in children's experiences of
      participation in perioperative care. RESULTS: The result showed that receiving
      preparatory information, lack of information regarding postoperative care and
      wanting to have detailed information are important factors for influencing
      children's participation. Interaction with healthcare professionals, in terms of
      being listened to, being a part of the decision-making and feeling trust, is
      important for children's participation in the decision-making process. Poor
      adaptation of the care environment to the children's needs, feeling uncomfortable
      while waiting and needs for distraction are examples of how the environment and
      the care in the operating theatre influence the children's experiences of
      participation. CONCLUSIONS: Efforts should be made to improve children's
      opportunities for participation in the context of perioperative care and further
      research is needed to establish international standards for information
      strategies and care environment that promotes children's participation in
      perioperative care. RELEVANCE TO CLINICAL PRACTICE: Nurse anaesthetists need to
      acquire knowledge and develop strategies for providing preparatory visits and
      information to children prior to surgery as well as reducing waiting times and
      creating environments with meaningful and tailored opportunities for distraction
      in perioperative care.

PMID- 26215897
TI  - Nanoscopic leg irons: harvesting of polymer-stabilized membrane proteins with
      antibody-functionalized silica nanoparticles.
AB  - Silica-based nanoparticles (SiNPs) are presented to harvest complex membrane
      proteins, which have been embedded into unilammelar polymersomes via in vitro
      membrane assisted protein synthesis (iMAP). Size-optimized SiNPs have been
      surface-modified with polymer-targeting antibodies, which are employed to harvest
      the protein-containing polymersomes. The polymersomes mimic the cellular
      membrane. They are chemically defined and preserve their structural-functional
      integrity as virtually any membrane protein species can be synthesized into such
      architecture via the ribosomal context of a cellular lysate. The SiNPs resemble
      'heavy leg irons' catching the polymersomes in order to enable gravity-based
      generic purification and concentration of such proteopolymersomes from the crude
      mixture of cellular lysates. 

PMID- 26215898
TI  - Ecological assessment of heart rate complexity: Differences between high- and low
      anxious adolescents.
AB  - Nonlinear measures can capture the complex structure of the heart beating, and
      recordings taken while the individual performs daily activities may help to
      understand the cardiac system's output in natural conditions. As healthy systems
      are characterized by having highly complex outputs, we hypothesized that the
      cardiac output from high anxious adolescents should be less complex than the
      output from their low anxious counterparts. In this study ECG was recorded for
      two hours in 50 adolescents while they performed regular school activities.
      Fractal dimension (FD), scaling exponents and multiscale entropy were calculated
      on the interbeat intervals time series. Both FD and entropy were significantly
      lower in the high-anxious group than the low-anxious group. These results suggest
      different heart-related regulation in adolescents who suffered from high anxious
      symptomatology. 

PMID- 26215899
TI  - Head-trunk kinematics during high-velocity-low-amplitude manipulation of the
      cervical spine in asymptomatic subjects: helical axis computation and anatomic
      motion modeling.
AB  - OBJECTIVE: This study aimed to analyze the in vivo 3-dimensional kinematics of
      the head during cervical manipulation including helical axis (HA) computation and
      anatomic motion representation. METHODS: Twelve asymptomatic volunteers were
      included in this study. An osteopathic practitioner performed 1 to 3
      manipulations (high-velocity and low-amplitude [HVLA] multiple component
      technique) of the cervical spine (between C2 and C5) with the patient in the
      sitting position. During manipulation, head motion was collected using an
      optoelectronic system and expressed relative to the thorax. Motion data were
      processed to analyze primary and coupled motions and HA parameters. Anatomic
      motion representation including HA was obtained. RESULTS: During manipulation,
      average maximal range of motion was 39 degrees  (SD, 6 degrees ), 21 degrees 
      (SD, 7 degrees ), and 8 degrees  (SD, 5 degrees ) for lateral bending (LB), axial
      rotation (AR), and flexion extension, respectively. For the impulse period,
      magnitude averaged of 8 degrees  (SD, 2 degrees ), 5 degrees  (SD, 2 degrees ),
      and 3 degrees  (SD, 2 degrees ), for LB, AR, and flexion extension, respectively.
      Mean impulse velocity was 139 degrees /s (SD, 39 degrees /s). Concerning AR/LB
      ratios, an average of 0.6 (SD, 0.3) was observed for global motion,
      premanipulation positioning, and impulse. Mean HA was mostly located ipsilateral
      to the impulse side and displayed an oblique orientation. CONCLUSION: This study
      demonstrated limited range of AR during cervical spine manipulation and provided
      new perspectives for the development of visualization tools, which might be
      helpful for practitioners and for the analysis of cervical manipulation using HA
      computation and anatomic representation of motion.

PMID- 26215900
TI  - Short-term effects of Mulligan mobilization with movement on pain, disability,
      and kinematic spinal movements in patients with nonspecific low back pain: a
      randomized placebo-controlled trial.
AB  - OBJECTIVE: The purpose of this clinical study was to compare the immediate- and
      short-term effects of lumbar Mulligan sustained natural apophyseal glides (SNAGs)
      on patients with nonspecific low back pain with respect to 2 new kinematic
      algorithms (KA) for range of motion and speed as well as pain, functional
      disability, and kinesiophobia. METHODS: This was a 2-armed randomized placebo
      controlled trial. Subjects, blinded to allocation, were randomized to either a
      real-SNAG group (n = 16) or a sham-SNAG group (n = 16). All patients were treated
      during a single session of real/sham SNAG (3 * 6 repetitions) to the lumbar spine
      from a sitting position in a flexion direction. Two new KA from a validated
      kinematic spine model were used and recorded with an optoelectronic device. Pain
      at rest and during flexion as well as functional disability and kinesiophobia was
      recorded by self-reported measures. These outcomes were blindly evaluated before,
      after treatment, and at 2-week follow-up in both groups. RESULTS: Of 6 variables,
      4 demonstrated significant improvement with moderate-to-large effect sizes (ES)
      in favor of the real-SNAG group: KA-R (P = .014, between-groups ES Cliff delta = 
      .52), pain at rest and during flexion (visual analog scale, P < .001; ES = -.73/
      .75), and functional-disability (Oswestry Disability Index, P = .003 and ES = 
      .61). Kinesiophobia was not considered to be significant (Tampa scale, P = .03)
      but presented moderate ES = -.46. Kinematic algorithms for speed was not
      significantly different between groups (P = .118) with a small ES = -.33. All 6
      outcome measures were significantly different (P <= .008) during within-group
      analysis (before and after treatment) only in the real-SNAG group. No serious or
      moderate adverse events were reported. CONCLUSION: This study showed evidence
      that lumbar spine SNAGs had a short-term favorable effect on KA-R, pain, and
      function in patients with nonspecific low back pain.

PMID- 26215901
TI  - Inertial sensors as real-time feedback improve learning posterior-anterior
      thoracic manipulation: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to analyze the effect of real-time
      feedback on the learning process for posterior-anterior thoracic manipulation
      (PATM) comparing 2 undergraduate physiotherapy student groups. METHODS: The study
      design was a randomized controlled trial in an educational setting. Sixty-one
      undergraduate physiotherapy students were divided randomly into 2 groups, G1 (n =
      31; group without feedback in real time) and G2 (n = 30; group with real-time
      feedback) participated in this randomized controlled trial. Two groups of
      physiotherapy students learned PATM, one using a traditional method and the other
      using real-time feedback (inertial sensor). Measures were obtained
      preintervention and postintervention. Intragroup preintervention and
      postintervention and intergroup postintervention scores were calculated. An
      analysis of the measures' stability was developed through an interclass
      correlation index. Time, displacement and velocity, and improvement (only between
      groups) to reach maximum peak and to reach minimum peak from maximum peak, total
      manipulation time, and stability of all outcome measures were the outcome
      measures. RESULTS: Statistically significant differences were found in all
      variables analyzed (intragroup and intergroup) in favor of G2. The values of
      interclass correlation ranged from 0.627 to 0.706 (G1) and between 0.881 and
      0.997 (G2). CONCLUSIONS: This study found that the learning process for PATM is
      facilitated when the student receives real-time feedback.

PMID- 26215902
TI  - Placebos for Knee Osteoarthritis: Reaffirmation of "Needle Is Better Than Pill".

PMID- 26215903
TI  - Corrigendum: Retrophylogenomics Place Tarsiers on the Evolutionary Branch of
      Anthropoids.

PMID- 26215904
TI  - Lower urinary tract symptoms after subtotal versus total abdominal hysterectomy:
      exploratory analyses from a randomized clinical trial with a 14-year follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: Lower urinary tract symptoms (LUTS) are common after
      hysterectomy and increase after menopause. We aimed to compare subtotal with
      total abdominal hysterectomy regarding LUTS, including urinary incontinence (UI)
      subtypes, 14 years after hysterectomy. Main results from this randomized clinical
      trial have been published previously; the analyses covered in this paper are
      exploratory. METHODS: We performed a long-term questionnaire follow-up of women
      in a randomized clinical trial (n = 319), from 1996 to 2000 comparing subtotal
      with total abdominal hysterectomy. Of the randomized women, ten had died and five
      had left Denmark; 304 women were contacted. For univariate analyses, a chi(2)
      test was used, and for multivariate analyses, we used logistic regression.
      RESULTS: The questionnaire was answered by 197 (64.7 %) women (subtotal 97; total
      100). More women had subjective stress UI (SUI) in the subtotal group (n = 60;
      62.5 %) compared with the total group (n = 45; 45 %), with a relative risk (RR)
      of 1.39 [95 % confidence interval (CI) 1.06-1.81; P = 0.014]. No difference was
      seen between subtotal and total abdominal hysterectomy in other LUTS. Factors
      associated with UI were UI prior to hysterectomy, local estrogen treatment, and
      body mass index (BMI) > 25 kg/m(2). High BMI was primarily associated with mixed
      UI (MUI) and urgency symptoms. Predictors of bothersome LUTS were UI and
      incomplete bladder emptying. CONCLUSIONS: The difference in the frequency of
      subjectively assessed UI between subtotal and total abdominal hysterectomy
      (published previously) is caused by a difference in subjectively assessed SUI; UI
      prior to hysterectomy and high BMI are related to UI 14 years after hysterectomy.
      TRIAL REGISTRATION: The trial is registered on clinicaltrials.gov under Nykoebing
      Falster County Hospital Record sj-268: Total versus subtotal hysterectomy:
      http://clinicaltrials.gov/ct2/show/NCT01880710?term=hysterectomy&rank=27.

PMID- 26215906
TI  - The effect of covalently linked RGD peptide on the conformation of
      polysaccharides in aqueous solutions.
AB  - Covalently modified polysaccharides are routinely used in tissue engineering due
      to their tailored biofunctionality. Understanding the effect of single-chain
      level modification on the solution conformation of the single chain, and more
      importantly on the self-assembly and aggregation of the ensemble of chains is
      expected to improve our ability to control network topology and the properties of
      the resulting gels. Attaching an RGD peptide to a polysaccharide backbone is a
      common procedure used to promote cell adhesion in hydrogel scaffolds. Recently it
      has been shown that the spatial presentation of the RGD sequences affects the
      cell behavior; thus, understanding the effects of grafted RGD on the
      conformational properties of the solvated polysaccharide chains is a prerequisite
      for rational design of polysaccharide-peptide based biomaterials. Here we
      investigate the effect of covalently linked G4RGDS on the conformational state of
      the individual chain and chain assemblies of alginate, chitosan, and hyaluronic
      acid (HA) in aqueous solutions. Two peptide fractions were studied using small
      angle X-ray scattering (SAXS) and rheology. In all cases, upon peptide
      conjugation structural differences were observed. Analysis of the scattering data
      shows evidence of clustering for a higher fraction of bound peptide. Moreover for
      all three polysaccharides the typical shear thinning behavior of the natural
      polysaccharide solutions is replaced by a Newtonian fluid behavior for the lower
      fraction conjugated peptide while a more pronounced shear thinning behavior is
      observed for the higher fraction. These results indicate that the fraction of the
      bounded peptide, determines the behavior of a polysaccharide-peptide conjugates
      in solution, regardless of the specific nature of the polysaccharide. 

PMID- 26215905
TI  - Transabdominal ultrasound to assess pelvic floor muscle performance during
      abdominal curl in exercising women.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess pelvic floor
      muscle (PFM) function using transabdominal ultrasound (TAUS) in women attending
      group exercise classes. Specific aims were to: (1) identify the ability to
      perform a correct elevating PFM contraction and (2) assess bladder-base movement
      during an abdominal curl exercise. METHODS: Ninety women participating in group
      exercise were recruited to complete a survey and TAUS assessment performed by two
      qualified Continence and Women's Health physiotherapists with clinical experience
      in ultrasound scanning. The assessment comprised three attempts of a PFM
      contraction and an abdominal curl exercise in crook lying. Bladder-base
      displacement was measured to determine correct or incorrect activation patterns.
      RESULTS: Twenty-five percent (n = 23) of women were unable to demonstrate an
      elevating PFM contraction, and all women displayed bladder-base depression on
      abdominal curl (range 0.33-31.2 mm). Parous women displayed, on average,
      significantly more bladder-base depression than did nulliparous women [15.5 (7.3)
      mm vs 11.4 (5.8) mm, p < 0.009). Sixty percent (n = 54) reported stress urinary
      incontinence (SUI). There was no association between SUI and the inability to
      perform an elevating PFM contraction (p = 0.278) or the amount of bladder-base
      depression with abdominal curl [14.1 (7.6) mm SUI vs 14.2 (6.7) mm non-SUI].
      CONCLUSIONS: TAUS identified that 25 % of women who participated in group
      exercise were unable to perform a correctly elevating PFM contraction, and all
      depressed the bladder-base on abdominal curl. Therefore, exercising women may be
      at risk of PFM dysfunction when performing abdominal curl activities.

PMID- 26215907
TI  - L-3-n-butylphthalide Promotes Neurogenesis and Neuroplasticity in Cerebral
      Ischemic Rats.
AB  - AIMS: This study investigated whether anticerebral ischemia new drug, l-3-n
      butylphthalide (l-NBP), improved behavioral recovery and enhanced hippocampal
      neurogenesis after cerebral ischemia in rats. METHODS AND RESULTS: The middle
      cerebral artery of rats was blocked for 2 h. The daily oral administrations of 30
      mg/kg l-NBP or vehicle were begun from the second day until the rats were
      sacrificed. L-NBP treatment markedly increased 5-bromo-2'-deoxyuridine (BrdU)
      positive cells in the hippocampal dentate gyrus (DG) of injured hemisphere on day
      28 after ischemia. The amount of newborn cells and newly mature neurons was also
      increased. The expressions of growth-associated protein-43 and synaptophysin were
      significantly elevated in l-NBP-treated rats. However, l-NBP markedly reduced the
      percentage of BrdU(+) /GFAP(+) cells. Additionally, the levels of catalytical
      subunit of protein kinase A (PKA), protein kinase B (Akt), and cAMP response
      element-binding protein (CREB) were significantly increased, and the activation
      of the signal transducer and activation of transcription 3 (STAT3) and the
      expressions of cleaved caspase-3 and Bax were obviously inhibited by l-NBP.
      Consequently, l-NBP attenuated the behavioral dysfunction. CONCLUSIONS: It first
      demonstrates that l-NBP may improve the behavioral outcome of cerebral ischemia
      by promoting neurogenesis and neuroplasticity. Activation of CREB and Akt and
      inhibition of STAT3 signaling might be involved in.

PMID- 26215908
TI  - A new method for characterizing hand dysfunction in cervical spondylotic
      myelopathy: a preliminary study.
AB  - STUDY DESIGN: A case-control investigation. OBJECTIVES: The objective of this
      study was to quantitatively study impaired ability to appropriately adjust pinch
      strength while holding a small object in patients with cervical spondylotic
      myelopathy (CSM). SETTING: Kochi Medical School Hospital, Japan. METHODS: The
      subjects consisted of 19 CSM patients who had frequent episodes of failing to
      grasp and hold small objects in their daily life (Group A), 13 CSM patients who
      did not experience such episodes (Group B) and 16 healthy subjects (Control
      Group). We continuously measured the dynamic internal pressure of a pneumatic
      rubber object called a blower pinched by the subject, following two different
      sets of instructions: (1) pinching with eyes open and with the minimal strength
      required to prevent dropping; and (2) maintaining a constant pinch strength at
      given levels with eyes closed. RESULTS: Compared with the other two groups, Group
      A subjects used a significantly (P<0.01) greater pinch strength to avoid dropping
      the blower held with eyes open and showed a significantly (P<0.01) greater
      deviation in pinch strength from the baseline values with eyes closed. These
      tendencies in Group A showed a significant correlation with the tactile
      perception threshold of the digits (P<0.01) but not with impairment of rapid
      repetitive movements of the digits that reflects spasticity. CONCLUSION: Our
      technique applied to CSM patients helps assess functional integrity primarily, if
      not exclusively, of the fasciculus cuneatus mediating the feedback signals from
      proprioceptive and cutaneous receptors in the digits, which are otherwise
      difficult to evaluate quantitatively.

PMID- 26215909
TI  - Reply 'Hyponatremia in spinal cord injury patients: new insight into
      differentiating between the dilution and depletion forms'.

PMID- 26215910
TI  - Predictors of musculoskeletal pain in the upper extremities of individuals with
      spinal cord injury.
AB  - INTRODUCTION: Increased demands on the upper extremities (UE) have been
      associated with a higher occurrence of musculoskeletal pain in individuals with
      spinal cord injury (SCI). STUDY DESIGN: This is a cross-sectional retrospective
      study. OBJECTIVE: The aim of this study was to characterize SCI subjects with
      musculoskeletal pain in the UE and to determine which variables could predict
      musculoskeletal pain in these individuals. SETTING: The study was conducted in
      SARAH Network of Rehabilitation Hospitals, Brasilia, Brazil. METHODS: Five
      hundred sixty-four electronic medical records were investigated through a
      retrospective, exploratory and descriptive analysis to identify individuals with
      UE pain. A logistic regression model was applied to estimate (odds ratios)
      whether gender, age, the level of injury, severity of injury, time of injury,
      body mass index, type of mobility and locomotion aid could predict the occurrence
      of musculoskeletal pain. RESULTS: The prevalence of musculoskeletal pain in the
      UE was 27.7%. The odds of having musculoskeletal pain were two times higher among
      woman and tetraplegic patients; those over 41 years of age had twice the
      frequency of pain than did those <24.7 years; <1 year of injury was a predictor
      of musculoskeletal pain, compared with the other quartiles (1.1-2.8, 2.9-6.8 and
      6.9+ years of injury). There were no differences between the wheelchair and
      ambulatory individuals. CONCLUSION: Female individuals, those with tetraplegia,
      aged >40 years and <1 year of injury showed an increased risk of musculoskeletal
      pain.

PMID- 26215911
TI  - Obituary for Air Marshal Amarjit Singh Chahal (25 December 1929-21 June 2015).

PMID- 26215912
TI  - Response to 'Hyponatremia in spinal cord injury patients: new insight into
      differentiating between the dilution and depletion forms'.

PMID- 26215913
TI  - Sacral neuromodulation in patients with neurogenic lower urinary tract
      dysfunction.
AB  - STUDY DESIGN: This is a retrospective chart analysis. OBJECTIVES: The objective
      of this study was to evaluate the effect of sacral neuromodulation (SNM) in
      patients with neurogenic lower urinary tract dysfunction (NLUTD). SETTINGS: This
      study was conducted in a spinal cord injury rehabilitation center in Switzerland.
      METHODS: The charts of all patients who underwent SNM (testing and/or permanent
      implantation) because of NLUTD at our institution between 2007 and 2013 were
      evaluated. Treatment outcomes and complications were recorded. RESULTS: A total
      of 50 patients, 30 women and 20 men, with a mean age of 46 (+/-14) years,
      fulfilled the inclusion criteria. The most frequent cause for SNM was spinal cord
      injury in 35 patients (70%). Median duration of the underlying disease was 9.5
      (+/-9.3) years. In all, 35 patients (70%) received a permanent implant. The
      complication rate was 16% (8/50). At the last follow-up, SNM was in use in 32
      patients. In 26 patients with SNM because of detrusor overactivity, voiding
      frequency per 24 h was significantly reduced from 9 to 6, and daily pad use rate
      was significantly improved (2.6 versus 0.6 pads per 24h). On comparing urodynamic
      assessment of detrusor function before and under SNM, no significant suppression
      of neurogenic detrusor overactivity (NDO) was detected. In nine patients with
      chronic neurogenic urinary retention, median postvoid residual urine was
      significantly reduced from 370 to 59 ml. In all, 94% of the patients were either
      very satisfied or satisfied with SNM. CONCLUSION: SNM might be an additional
      therapy option in carefully selected patients with NLUTD. On the basis of our
      results, urodynamic evaluation before SNM is mandatory, as the procedure does not
      seem to be suited to significantly alleviate NDO.

PMID- 26215914
TI  - Energetic and cardiovascular responses to treadmill walking and stationary
      cycling in subjects with incomplete spinal cord injury.
AB  - STUDY DESIGN: Randomized controlled trail. OBJECTIVES: To investigate if people
      with incomplete spinal cord injury (SCI) can perform high-intensity weight
      bearing exercise by comparing cardiovascular responses at maximal workloads
      during stationary cycling and treadmill walking, and to explore mechanical
      efficiencies at sub-maximal workloads. SETTING: Sunnaas Rehabilitation Hospital,
      Nesoddtangen, Norway. METHODS: Fifteen people with incomplete SCI and 15 healthy
      control subjects performed sub-maximal and maximal exercise tests of both
      stationary cycling and uphill treadmill walking on separate days. Oxygen uptake
      (VO(2); l min(-1) and ml kg(-1) min(-1)), carbon dioxide production (VCO(2); l
      min(-1)), respiratory exchange ratio (RER) and heart rate (HR) were continuously
      measured throughout the tests. RESULTS: The SCI group showed no significant
      differences in peak VO(2) (2.42+/-0.68 l min(-1) versus 2.58+/-0.76 l min(-1),
      P=0.19) or other cardiovascular responses at maximal workloads for stationary
      cycling as compared with uphill treadmill walking, except for higher RER during
      the cycle test. The control subjects exhibited a significantly higher peak VO(2)
      during the treadmill test as compared with the cycle test (P=0.007). Both groups
      had lower mechanical efficiency when walking as compared with cycling, but the
      mean difference between cycling and walking was not significantly different
      between the groups during sub-maximal workloads (P >0.24). CONCLUSION: Subjects
      with incomplete SCI were able to perform high-intensity weight-bearing exercise
      and exhibited similar mechanical efficiencies at sub-maximal workloads as healthy
      controls. Uphill walking might be a good alternative to weight-bearing exercise
      for increasing the physical capacity of people with incomplete SCI.

PMID- 26215915
TI  - Functional assessment of SCI patients by FIM: yes or no?

PMID- 26215916
TI  - A potential anti-allodynic mechanism of GDNF following L5 spinal nerve ligation;
      Mitigation of NPY up-regulation in the touch sense pathway.
AB  - Intrathecal delivery of glial cell line-derived neurotrophic factor (GDNF)
      reverses mechanical allodynia after 5th lumbar (L5) spinal nerve ligation (SNL).
      However, the molecular mechanism behind this process is not fully understood.
      Following sciatic nerve injury, primary afferent neurons in the injured dorsal
      root ganglion (DRG) begin to express neuropeptide Y (NPY) that is absent in
      normal DRG. The aim of the current study was to determine the relationship of
      this de novo expression of NPY and the anti-allodynic effect of GDNF. Following
      L5 SNL, 73% of neurons began to express NPY mRNA in the ipsilateral L5 DRG and
      robust NPY-immunoreactive fibers appeared in the ipsilateral GN where the touch
      sense mediating A-fiber primary afferents from the hindpaw terminate. Seven
      daylong intrathecal infusion of GDNF at the L5 DRG level, starting on day three
      when mechanical allodynia had fully developed, reversed once-established these
      changes. The GN neurons normally expressed NPY Y1 receptor, but not Y2, Y4, or Y5
      receptors, and L5 SNL did not change the expression pattern. Bolus intracisternal
      injection of BIBP3226, a Y1 receptor antagonist, dose-dependently reversed
      mechanical allodynia. We demonstrated that GDNF reversed once-established
      mechanical allodynia as well as NPY induction in the touch-sense processing
      pathway. NPY could facilitate touch-sense processing by Y1 receptor in the
      gracile nucleus after peripheral nerve injury. GDNF may exert anti-allodynic
      effects through mitigation of this NPY up-regulation. The effectiveness of
      delayed treatment further indicates the therapeutic potential of GDNF on
      neuropathic pain. 

PMID- 26215917
TI  - The hypothalamic transcriptional response to stress is severely impaired in
      offspring exposed to adverse nutrition during gestation.
AB  - Gestation is a time of profound vulnerability, as insults during pregnancy
      increase the lifelong risk of morbidity for the offspring. Increasingly, maternal
      diet is recognized as a key factor influencing the developing fetus. Poor-quality
      maternal diets, whether they provide an excess or an insufficiency of nutrients,
      lead to overt gestational growth disturbances in the offspring, and elevated risk
      for a common cluster of metabolic and mental disorders. Metabolic disturbances,
      particularly a substantially increased risk of obesity, have been linked in both
      maternal overnutrition and maternal undernutrition with abnormal development of
      the offspring hypothalamus, which serves a vital role in the central regulation
      of feeding. Additionally, the hypothalamus also coordinates physiological
      responses to stressors, and may thus play a role in vulnerability to psychiatric
      disease in these offspring. We examined hypothalamic molecular and endocrine
      responses to a psychological stressor (restraint) and a physiological stressor
      (lipopolysaccharide; LPS) in adult offspring from dams fed a high-fat diet or a
      low-protein diet during gestation and lactation. Targeted gene expression in the
      hypothalamus for 26 genes of interest sorted via hierarchical clustering revealed
      that the vast majority of these transcripts were substantially upregulated by
      both stressors. In contrast, offspring of maternal high-fat and low-protein diets
      mounted essentially no gene expression response to either stressor. However, male
      and female offspring of all conditions showed elevated hypothalamic-pituitary
      adrenal glucocorticoid responses to both stressors, though the recovery of
      corticosterone responses after stress termination was significantly impaired in
      offspring of poor-quality maternal diets. Overall, it appears that the ability of
      the hypothalamus to respond in the immediate aftermath of stressful experiences
      is severely impaired in offspring of poor-quality maternal diets, regardless of
      whether the diet provided insufficient nutrients or excessive nutrients.

PMID- 26215918
TI  - Hippocampal cell fate regulation by chronic cocaine during periods of adolescent
      vulnerability: Consequences of cocaine exposure during adolescence on behavioral
      despair in adulthood.
AB  - Given that adolescence represents a critical moment for shaping adult behavior
      and may predispose to disease vulnerability later in life, the aim of this study
      was to find a vulnerable period during adolescence in which hippocampal cell fate
      regulation was altered by cocaine exposure, and to evaluate the long-term
      consequences of a cocaine experience during adolescence in affecting hippocampal
      plasticity and behavioral despair in adulthood. Study I: Male rats were treated
      with cocaine (15mg/kg, i.p.) or saline for 7 consecutive days during adolescence
      (early post-natal day (PND) 33-39, mid PND 40-46, late PND 47-53). Hippocampal
      plasticity (i.e., cell fate regulation, cell genesis) was evaluated 24h after the
      last treatment dose during the course of adolescence (PND 40, PND 47, PND 54).
      Study II: The consequences of cocaine exposure during adolescence (PND 33-39 or
      PND 33-46; 7 or 14days) were measured in adulthood at the behavioral (i.e.,
      forced swim test, PND 62-63) and molecular (hippocampal cell markers, PND 64)
      levels. Chronic cocaine during early adolescence dysregulated FADD forms only in
      the hippocampus (HC), as compared to other brain regions, and during mid
      adolescence, impaired cell proliferation (Ki-67) and increased PARP-1 cleavage (a
      cell death maker) in the HC. Interestingly, chronic cocaine exposure during
      adolescence did not alter the time adult rats spent immobile in the forced swim
      test. These results suggest that this paradigm of chronic cocaine administration
      during adolescence did not contribute to the later manifestation of behavioral
      despair (i.e., one pro-depressive symptom) as measured by the forced swim test in
      adulthood. 

PMID- 26215920
TI  - White matter differences between multiple system atrophy (parkinsonian type) and
      Parkinson's disease: A diffusion tensor image study.
AB  - The clinical differential diagnosis between the Parkinson variant of multiple
      system atrophy (MSA-P) and Parkinson's disease (PD) is difficult in early stages.
      To identify objective markers for differential diagnosis, we combined the novel
      tract-based spatial statistics (TBSS) and region of interest (ROI) analyses for
      the first time to investigate three groups (15 MSA-P, 20 PD patients and 20
      controls) with diffusion tensor imaging data. By TBSS, we performed pairwise
      comparisons of fractional anisotropy (FA), mean diffusivity, radial diffusivity
      (RD) and axial diffusivity maps. The clusters with significant differences
      between MSA-P and PD were used as ROIs for further analyses. FA/RD values in
      bilateral corticospinal tract (CST) and left anterior thalamic radiation (ATR) in
      MSA-P were significantly different from PD or controls, and significantly
      correlated with clinical data. These findings indicated that the abnormalities of
      left ATR and bilateral CST were specific for MSA-P relative to PD or controls,
      and seemed to be promising for differential diagnosis. Furthermore, it may be
      useful for severity assessment of MSA-P. 

PMID- 26215919
TI  - Electron tomographic structure and protein composition of isolated rat
      cerebellar, hippocampal and cortical postsynaptic densities.
AB  - Electron tomography and immunogold labeling were used to analyze similarities and
      differences in the morphology and protein composition of postsynaptic densities
      (PSDs) isolated from adult rat cerebella, hippocampi, and cortices. There were
      similarities in physical dimensions and gross morphology between cortical,
      hippocampal and most cerebellar PSDs, although the morphology among cerebellar
      PSDs could be categorized into three distinct groups. The majority of cerebellar
      PSDs were composed of dense regions of protein, similar to cortical and
      hippocampal PSDs, while others were either composed of granular or lattice-like
      protein regions. Significant differences were found in protein composition and
      organization across PSDs from the different brain regions. The signaling protein,
      betaCaMKII, was found to be a major component of each PSD type and was more
      abundant than alphaCaMKII in both hippocampal and cerebellar PSDs. The scaffold
      molecule PSD-95, a major component of cortical PSDs, was found absent in a
      fraction of cerebellar PSDs and when present was clustered in its distribution.
      In contrast, immunogold labeling for the proteasome was significantly more
      abundant in cerebellar and hippocampal PSDs than cortical PSDs. Together, these
      results indicate that PSDs exhibit remarkable diversity in their composition and
      morphology, presumably as a reflection of the unique functional demands placed on
      different synapses. 

PMID- 26215921
TI  - Food reward without a timing component does not alter the timing of activity
      under positive energy balance.
AB  - Circadian clocks drive daily rhythms in physiology and behavior which allow
      organisms to anticipate predictable daily changes in the environment. In most
      mammals, circadian rhythms result in nocturnal activity patterns although
      plasticity of the circadian system allows activity patterns to shift to different
      times of day. Such plasticity is seen when food access is restricted to a few
      hours during the resting (light) phase resulting in food anticipatory activity
      (FAA) in the hours preceding food availability. The mechanisms underlying FAA are
      unknown but data suggest the involvement of the reward system and homeostatic
      regulation of metabolism. We previously demonstrated the isolated effect of
      metabolism by inducing diurnality in response to energetic challenges. Here the
      importance of reward timing in inducing daytime activity is assessed. The daily
      activity distribution of mice earning palatable chocolate at their preferred time
      by working in a running wheel was compared with that of mice receiving a timed
      palatable meal at noon. Mice working for chocolate (WFC) without being
      energetically challenged increased their total daily activity but this did not
      result in a shift to diurnality. Providing a chocolate meal at noon each day
      increased daytime activity, identifying food timing as a factor capable of
      altering the daily distribution of activity and rest. These results show that
      timing of food reward and energetic challenges are both independently sufficient
      to induce diurnality in nocturnal mammals. FAA observed following timed food
      restriction is likely the result of an additive effect of distinct regulatory
      pathways activated by energetic challenges and food reward. 

PMID- 26215922
TI  - European Medicines Agency approves first malaria vaccine.

PMID- 26215923
TI  - Configuration-Dependent Photoinduced Electron Transfer in Diastereomeric
      Naphthalene-Amino-Naphthalene Triads.
AB  - Novel diastereomeric triads containing two naphthalene chromophores have been
      designed in which an electron-donating amine moiety is covalently integrated into
      the connecting bridge. Photophysical studies (steady-state and time-resolved
      fluorescence) in solvents of different polarity have been performed. A remarkable
      stereodifferentiation in the intramolecular fluorescence quenching was found in
      acetonitrile. Laser flash photolysis gave rise to naphthalene-derived radical
      cations, which were also quenched by the amine with an even higher degree of
      stereodifferentiation. The results are in agreement with thermodynamic
      estimations and indicate that photoinduced electron transfer (PET) is the main
      quenching pathway. Furthermore, theoretical calculations have allowed us to
      explain the experimentally observed stereodifferentiation in PET quenching. 

PMID- 26215924
TI  - Exploring structural and electronic effects in three isomers of
      tris{bis(trifluoromethyl)phenyl}borane: towards the combined electrochemical
      frustrated Lewis pair activation of H2.
AB  - Three structural isomers of tris{bis(trifluoromethyl)phenyl}borane have been
      studied as the acidic component of frustrated Lewis pairs. While the 3,5
      substituted isomer is already known to heterolytically cleave H2 to generate a
      bridging-hydride; ortho-substituents in the 2,4- and 2,5-isomers quench such
      reactivity through electron donation into the vacant boron pz orbital and steric
      blocking of the boron centre; as shown by electrochemical, structural and
      computational studies. Electrochemical studies of the corresponding borohydrides
      identify that the two-electron oxidation of terminal-hydrides occurs at more
      positive potentials than observed for [HB(C6F5)3](-), while the bridging-hydride
      oxidizes at a higher potential still, comparable to that of free H2. 

PMID- 26215925
TI  - Tailoring the hybrid palliation for hypoplastic left heart syndrome: A simulation
      study using a lumped parameter model.
AB  - The results of Hybrid procedure (HP) for the hypoplastic left heart syndrome
      (HLHS) depend on several variables: pulmonary artery banding tightness (PAB),
      atrial septal defect size (ASD) and patent ductus arteriosus stent size (PDA). A
      HP complication could be the aortic coarctaction (CoAo). The reverse Blalock
      Taussig shunt (RevBT) placement was proposed to avoid CoAo effects. This work
      aims at developing a lumped parameter model (LPM) to investigate the effects of
      the different variables on HP haemodynamics. A preliminary verification was
      performed collecting measurements on a newborn HLHS patient to calculate LPM
      input parameters to reproduce patient's baseline. Results suggest that
      haemodynamics is affected by ASD (ASD: 0.15-0.55 cm, pulmonary to systemic flow
      ratio Qp/Qs: 0.73-1, cardiac output (CO): 1-1.5 l/min and ventricular stroke work
      SW: 336-577 ml mmHg) and by the PAB diameter (PAB: 0.07-0.2 cm, Qp/Qs: 0.46-2.1,
      CO: 1.3-1.6 l/min and SW: 591-535 ml mmHg). Haemodynamics was neither affected by
      RevBT diameter nor by PDA diameter higher than 0.2 cm. RevBT implantation does
      not change the HP haemodynamics, but it can make the CoAo effect negligible. LPM
      could be useful to support clinical decision in complex physiopathology and to
      calibrate and personalise the parameters that play a role on flow distribution.

PMID- 26215926
TI  - Two Splice Variants of Y Chromosome-Located Lysine-Specific Demethylase 5D Have
      Distinct Function in Prostate Cancer Cell Line (DU-145).
AB  - One of the major objectives of the Human Y Chromosome Proteome Project is to
      characterize sets of proteins encoded from the human Y chromosome. Lysine (K)
      specific demethylase 5D (KDM5D) is located on the AZFb region of the Y chromosome
      and encodes a JmjC-domain-containing protein. KDM5D, the least well-documented
      member of the KDM5 family, is capable of demethylating di- and trimethyl H3K4. In
      this study, we detected two novel splice variants of KDM5D with lengths of 2650bp
      and 2400bp that correspond to the 100 and 80 kDa proteins in the human prostate
      cancer cell line, DU-145. The knockdown of two variants using the short
      interfering RNA (siRNA) approach increased the growth rate of prostate cancer
      cells and reduced cell apoptosis. To explore the proteome pattern of the cells
      after KDM5D downregulation, we applied a shotgun label-free quantitative
      proteomics approach. Of 820 proteins present in all four replicates of two
      treatments, the abundance of 209 proteins changed significantly in response to
      KDM5D suppression. Of these, there were 102 proteins observed to be less abundant
      and 107 more abundant in KDM5D knockdown cells compared with control cells. The
      results revealed that KDM5D knockdown altered the abundance of proteins involved
      in RNA processing, protein synthesis, apoptosis, the cell cycle, and growth and
      proliferation. In conjunction, these results provided new insights into the
      function of KDM5D and its splice variants. The proteomics data are available at
      PRIDE with ProteomeXchange identifier PXD000416. 

PMID- 26215927
TI  - Systemic acute phase proteins response in calves experimentally infected with
      Eimeria zuernii.
AB  - Acute phase proteins (APPs) have been demonstrated to be useful in evaluating
      general health stress and diseases in cattle. Serum amyloid A (SAA) and
      haptoglobin (Hp) are APPs that are produced during inflammation, and likely play
      a role in host immunological defence against Eimeria infection and the associated
      intestinal tissue damage. We investigated the involvement of SAA and HP in an
      experimental study, including three groups of calves: a control group (group 0,
      n=11), and two groups infected with either 150,000 or 250,000 Eimeria zuernii
      oocysts (group 1 (n=11) and group 2 (n=12), respectively). The calves were
      monitored for 28 days and data was collected on oocyst excretion, faecal score,
      animal weight, and SAA and Hp serum concentrations. Generalized linear mixed
      models showed that the clinical symptoms, indicated by an increase in the number
      of oocysts in the faeces and severe diarrhoea, manifested at patency for group 1
      and 2. Serum Hp and SAA levels also increased during this period. Hp appeared to
      be a more sensitive marker than SAA, and differences between groups 1 and 2 were
      observed only for Hp. Linear regression models showed a negative association
      between weight gain and Hp concentrations, calculated as the area under the curve
      (AUC) during the overall experimental period and the patency period. A similar
      result was seen for SAA only during the patency period. This result supports the
      assumption that reduced weight gain due to E. zuernii infection is an
      immunologically driven process that involves an increase in APPs. A random
      intercept regression model of oocyst shedding groups showed that calves shedding
      1-500 oocysts had reduced concentrations of Hp, indicating that a different
      immunological reaction occurs during mild shedding of E. zuernii oocysts than
      during more intensive shedding. A similar model was used to examine associations
      between faecal scores and Hp concentrations for each group. Group 2 calves with
      haemorrhagic diarrhoea displayed higher Hp levels than calves in that group with
      lower faecal scores, which may be in response to an increased demand for Hp in
      the repair process as a result of haemolysis. APPs seem to play an important role
      in determining the course of E. zuernii infection in calves, which may enhance
      our understanding of the immunological reaction and development of this disease. 

PMID- 26215928
TI  - Expression patterns and structural modelling of Hsp70 and Hsp90 in a fish-borne
      zoonotic nematode Anisakis pegreffii.
AB  - Heat shock proteins (HSPs) are essential molecular chaperones that are highly
      conserved across organisms. They have a pivotal function in responding to thermal
      stress and are responsible for many cellular functions. Here, we aimed to
      elucidate the possible roles of Hsp70 and Hsp90 in the life cycle of the
      parasitic nematode Anisakis, particularly third- and fourth-stage larvae, from
      cold-blooded fish to warm-blooded marine mammals or accidentally to human hosts.
      We examined the expression profiles of Hsp70 and Hsp90 in different developmental
      stages of Anisakis pegreffii. The open reading frame of Hsp70 of A. pegreffii was
      1950 bp, and deduced amino acid sequence showed high homology with those of other
      nematodes. Heatmap analysis revealed sequence identity of Hsp70 and Hsp90 in 13
      important parasitic species, human and yeast. On heatmap and phylogenetic
      analysis, ApHsp70 and ApHsp90 shared the highest amino acid sequence identity
      with other nematodes and formed a monophyletic clade. The three-dimensional (3D)
      structure prediction of the newly characterized ApHsp70 and known ApHsp90 gene
      showed highly conserved motifs between A. pegreffii and other species.
      Quantitative real-time PCR and western blot analysis revealed higher mRNA and
      protein expression for ApHsp70 and ApHsp90 in fourth- than third-stage larvae,
      with higher mRNA and protein expression for ApHsp70 than ApHsp90. ApHsp70 and
      ApHsp90 may play important roles in Anisakis in response to thermal stress and
      might be important molecules in the development of A. pegreffii, which has
      implications for its control.

PMID- 26215929
TI  - Metaphylactic treatment strategies with toltrazuril and diclazuril and growth
      performance of buffalo calves exposed to a natural eimeria infection.
AB  - Five controlled field trials were conducted in southern Italy to evaluate the
      effect of metaphylactic treatment strategies of toltrazuril and diclazuril for
      the control of coccidiosis in water buffaloes naturally infected by Eimeria spp.
      The 5 farms were divided into two types (A and B) according to their management
      system (individual or collective breeding of buffalo calves). In the farms of
      type A (no. 3), the buffalo calves were bred in individual boxes from the birth
      to the 7th/8th week of age and then transferred to concrete based pens; in the
      farms of type B (no. 2) the calves were bred in groups on concrete based pens
      from the birth. On each farm, 36 calves aged 5 weeks were divided at random into
      three similar groups of 12. One group was treated with toltrazuril (TOL), the
      second group was treated with diclazuril (DIC) and the third group was remained
      as untreated control group (CONT). On each farm the calves were weighed weekly
      and clinically examined. In the 5 buffalo farms the average oocyst excretion
      decreased significantly in both the treated groups (TOL and DIC), however the TOL
      groups had significantly low counts than the DIC groups. The body-weight gains
      recorded fortnightly were significantly higher in the TOL groups (range=5.4-8.1
      kg) compared to the DIC (range=1.7-3.1 kg).

PMID- 26215930
TI  - Paired analysis of the microbiota of surface mucus and whole-tissue specimens in
      patients with chronic rhinosinusitis.
AB  - BACKGROUND: The role of bacteria in the pathogenesis of chronic rhinosinusitis
      (CRS) remains uncertain. Recent evidence suggests that bacteria are able to
      establish microcolonies within the underlying mucosa. However, to date there has
      been no systematic comparison of bacterial community composition and diversity in
      the surface mucosa with that of the underlying tissue. METHODS: Paired swabs and
      whole-tissue samples were collected from the middle meatus of 9 patients with CRS
      undergoing endoscopic sinus surgery. The bacterial composition and diversity of
      the samples were determined using 16S rRNA gene amplicon pyrosequencing. RESULTS:
      The bacterial communities of both swabs and tissues were dominated by known
      residents of the sinonasal cavity such as Staphylococcus, Corynebacterium,
      Prevotella, and Peptoniphilus. Although bacterial diversity (richness) did not
      differ between the 2 groups of samples, there were significant differences in the
      composition of bacterial communities. Molecular analyses revealed a large amount
      of interpersonal variation between patients. CONCLUSION: Swab and tissue samples
      revealed similar bacterial diversity to each other and to that of other
      microbiota studies reported in the CRS literature. However, bacterial composition
      was significantly different between the 2 sample types, even though the tissue
      biopsies also comprise bacteria from the surface. We speculate that the bacteria
      on the surface seed the underlying tissue via the damaged epithelium in CRS
      patients, which over time develops into a distinct bacterial community.

PMID- 26215931
TI  - Angiopreventive versus angiopromoting effects of allopurinol in the murine sponge
      model.
AB  - Recent data has indicated that, besides its classical therapeutic indication in
      hyperurecemia and gout, xanthine oxidase inhibitors can be used to various forms
      of ischemia and other types of tissue and vascular injuries. We tested the
      hypothesis that allopurinol, an inhibitor of xanthine oxidase (XO), might
      modulate acute and/or chronic inflammatory angiogenesis induced by subcutaneous
      implantation of synthetic matrix in mice. C57/BL6 male mice (6-7 weeks) were
      implanted with polyether-polyurethane sponge discs. The animals received by oral
      gavage 1.0mg/kg of allopurinol for six consecutive days in two treatment regimen.
      In the first series of experiments, the treatment was initiated 24h post
      implantation and the implants were removed at day 7 post-implantation. For the
      assessment of the effect of the compound on chronic inflammation, the treatment
      was initiated at day 8 post-implantation and the implants removed 14days post
      implantation. Angiogenesis as determined by hemoglobin content, VEGF levels and
      number of vessels intraimplant, and inflammation (myeloperoxidase -MPO, n-acetyl
      beta-d-glucosaminidase -NAG, TNF-alpha and CCL2 levels) were reduced by
      allopurinol treatment in acute phase. Similarly, the treatment inhibited nitric
      oxide and H2O2 production. However, fibrogenesis determined by collagen
      deposition and levels of TGF-beta1 increased in the implants after allopurinol
      treatment. In marked contrast with the effects when the treatment initiated 24h
      post-implantation, allopurinol increased angiogenesis and inflammation but
      reduced collagen and TGF-beta1 levels intra-implant, when the treatment was
      started during the chronic inflammatory process. The dual effects of allopurinol
      described here, extend its range of actions as a potential agent able to modulate
      the components of the fibrovascular tissue present in both physiological (healing
      processes) as well as in chronic fibroproliferative diseases. These modulatory
      effects depended on the phase at which the treatment was initiated. 

PMID- 26215932
TI  - Shear Bond Strength between Fiber-Reinforced Composite and Veneering Resin
      Composites with Various Adhesive Resin Systems.
AB  - PURPOSE: The aim of this research was to evaluate the shear bond strength of
      different laboratory resin composites bonded to a fiber-reinforced composite
      substrate with some intermediate adhesive resins. MATERIALS AND METHODS: Mounted
      test specimens of a bidirectional continuous fiber-reinforced substrate
      (StickNet) were randomly assigned to three equal groups. Three types of
      commercially available veneering resin composites - BelleGlass(r), Sinfony(r),
      and GC Gradia(r) were bonded to these specimens using four different adhesive
      resins. Half the specimens per group were stored for 24 hours; the remaining were
      stored for 30 days. There were 10 specimens in the test group (n). The shear bond
      strengths were calculated and expressed in MPa. Data were analyzed statistically,
      and variations in bond strength within each group were additionally evaluated by
      calculating the Weibull modulus. RESULTS: Shear bond values of those composites
      are influenced by the different bonding resins and different indirect composites.
      There was a significant difference in the shear bond strengths using different
      types of adhesive resins (p = 0.02) and using different veneering composites (p <
      0.01). Belle-Glass(r) had the highest mean shear bond strength when bonded to
      StickNet substrate using both Prime & Bond NT and OptiBond Solo Plus. Sinfony(r)
      composite resin exhibited the lowest shear bond strength values when used with
      the same adhesive resins. The adhesive mode of failure was higher than cohesive
      with all laboratory composite resins bonded to the StickNet substructure at both
      storage times. Water storage had a tendency to lower the bond strengths of all
      laboratory composites, although the statistical differences were not significant.
      CONCLUSION: Within the limitations of this study, it was found that bonding of
      the veneering composite to bidirectional continuous fiber-reinforced substrate is
      influenced by the brand of the adhesive resin and veneering composite.

PMID- 26215933
TI  - JC polyomavirus nephropathy confirmed by using an in-house polymerase chain
      reaction method.
AB  - We report the case of an isolated JC virus (JCV) infection, without co-infection
      by polyoma BK virus (BKV), associated with nephropathy 4 years after kidney
      transplantation. Clinical suspicion followed the observation of a decrease in
      estimated glomerular filtration rate (eGFR) and a renal allograft biopsy
      revealing polyomavirus-associated tubulointerstitial nephritis and positivity for
      SV40. An in-house real-time polymerase chain reaction assay, targeting the
      presence of JCV and the absence of BKV in biopsy tissue, confirmed diagnosis.
      Thirteen months after diagnosis, and following therapeutic measures, eGFR remains
      stable. 

PMID- 26215934
TI  - Are multiple primary outcomes analysed appropriately in randomised controlled
      trials? A review.
AB  - OBJECTIVES: To review how multiple primary outcomes are currently considered in
      the analysis of randomised controlled trials. We briefly describe the methods
      available to safeguard the inferences and to raise awareness of the potential
      problems caused by multiple outcomes. METHODS/DESIGN: We reviewed randomised
      controlled trials (RCTs) in neurology and psychiatry disease areas, as these
      frequently analyse multiple outcomes. We reviewed all published RCTs from July
      2011 to June 2014 inclusive in the following high impact journals: The New
      England Journal of Medicine, The Lancet, The American Journal of Psychiatry, JAMA
      Psychiatry, The Lancet Neurology and Neurology. We examined the information
      presented in the abstract and the methods used for sample size calculation and
      statistical analysis. We recorded the number of primary outcomes, the methods
      used to account for multiple primary outcomes, the number of outcomes discussed
      in the abstract and the number of outcomes used in the sample size calculation.
      RESULTS: Of the 209 RCTs that we identified, 60 (29%) analysed multiple primary
      outcomes. Of these, 45 (75%) did not adjust for multiplicity in their analyses.
      Had multiplicity been addressed, some of the trial conclusions would have
      changed. Of the 15 (25%) trials which accounted for multiplicity, Bonferroni's
      correction was the most commonly used method. CONCLUSIONS: Our review shows that
      trials with multiple primary outcomes are common. However, appropriate steps are
      not usually taken in most of the analyses to safeguard the inferences against
      multiplicity. Authors should state their chosen primary outcomes clearly and
      justify their methods of analysis.

PMID- 26215935
TI  - One in Three Patients With Cancer Meets the Criteria for Mental Disorders: What
      Does That Mean?

PMID- 26215936
TI  - Is the Benign Breast Disease Breast Cancer Model Well Calibrated?

PMID- 26215937
TI  - Reply to F.V. Negri et al.

PMID- 26215938
TI  - Does Radiotherapy Plus Androgen-Deprivation Therapy Represent the Best Treatment
      Approach in Elderly Patients With Locally Advanced Prostate Cancer?

PMID- 26215939
TI  - Optimal Concurrent Chemoradiotherapy Regimen in Non-Small-Cell Lung Cancer:
      Prospective, Randomized Data Still Required.

PMID- 26215940
TI  - Reply to J. Dekker et al.

PMID- 26215941
TI  - Postoperative Radiotherapy for Pathologic N2 Non-Small-Cell Lung Cancer Treated
      With Adjuvant Chemotherapy: Need for Randomized Evidence.

PMID- 26215942
TI  - Patient-Derived Xenografts for Investigation of Acquired Resistance in Oncogene
      Driven Cancers: Building a Better Mousetrap.

PMID- 26215943
TI  - Reply to D.A. Palma et al and A. Addeo et al.

PMID- 26215944
TI  - A Bone to Pick Regarding Use of Magnetic Resonance Imaging to Begin Treatment in
      Patients With Asymptomatic Multiple Myeloma.

PMID- 26215945
TI  - Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With
      Lobular Carcinoma in the BIG 1-98 Trial.
AB  - PURPOSE: To evaluate the relative effectiveness of letrozole compared with
      tamoxifen for patients with invasive ductal or lobular carcinoma. PATIENTS AND
      METHODS: Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or
      classic invasive lobular carcinoma (ILC) who were randomly assigned onto the
      Breast International Group (BIG) 1-98 trial and who had centrally reviewed
      pathology data were included (N = 2,923). HER2-negative IDC and ILC were
      additionally classified as hormone receptor-positive with high (luminal B [LB] 
      like) or low (luminal A [LA] -like) proliferative activity by Ki-67 labeling
      index. Survival analyses were performed with weighted Cox models that used
      inverse probability of censoring weighted modeling. RESULTS: The median follow-up
      time was 8.1 years. In multivariable models for disease-free survival (DFS),
      significant interactions between treatment and histology (ILC or IDC; P = .006)
      and treatment and subgroup (LB like or LA like; P = .01) were observed. In the
      ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole
      for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA
      subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a
      significant 35% reduction in the hazard of a DFS event with letrozole for the LB
      subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments
      was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20).
      CONCLUSION: The magnitude of benefit of adjuvant letrozole is greater for
      patients diagnosed with lobular carcinoma versus ductal carcinoma.

PMID- 26215947
TI  - Reply to G. Gandaglia et al and K. Lu.

PMID- 26215946
TI  - A Practical Solution for Dyspareunia in Breast Cancer Survivors: A Randomized
      Controlled Trial.
AB  - PURPOSE: Dyspareunia is common in breast cancer survivors because of low
      estrogen. This study explored whether dyspareunia is introital pain, preventable
      with analgesic liquid. PATIENTS AND METHODS: In a randomized, controlled, double
      blind trial, estrogen-deficient breast cancer survivors with severe penetrative
      dyspareunia applied either saline or 4% aqueous lidocaine to the vulvar vestibule
      for 3 minutes before vaginal penetration. After a 1-month blinded trial of
      patient-assessed twice-per-week tampon insertion or intercourse, all patients
      received lidocaine for 2 months in an open-label trial. The primary outcome was
      patient-related assessment of penetration pain on a scale of zero to 10.
      Secondary outcomes were sexual distress (Female Sexual Distress Scale), sexual
      function (Sexual Function Questionnaire), and resumption of intercourse.
      Comparisons were made with the Mann-Whitney U and Wilcoxon signed rank test with
      significance set at P < .05. RESULTS: In all, 46 patients, screened to exclude
      those with pelvic muscle and organ pain, uniformly had clinical evidence of
      severe vulvovaginal atrophy, dyspareunia (median pain score, 8 of 10;
      interquartile range [IQR], 7 to 9), increased sexual distress scores (median,
      30.5; IQR, 23 to 37; abnormal, > 11), and abnormal sexual function. Users of
      lidocaine reported less pain during intercourse in the blinded phase (median
      score of 1.0 compared with saline score of 5.3; P = .007). After open-label
      lidocaine use, 37 (90%) of 41 reported comfortable penetration. Sexual distress
      decreased (median score, 14; IQR, 3 to 20; P < .001), and sexual function
      improved in all but one domain. Of 20 prior abstainers from intercourse who
      completed the study, 17 (85%) had resumed comfortable penetrative intimacy. No
      partners reported penile numbness. CONCLUSION: Breast cancer survivors with
      menopausal dyspareunia can have comfortable intercourse after applying liquid
      lidocaine compresses to the vulvar vestibule before penetration.

PMID- 26215948
TI  - Reply to K. Lu.

PMID- 26215949
TI  - Reply to D.L. Cooper.

PMID- 26215950
TI  - Paclitaxel Given Once Per Week With or Without Bevacizumab in Patients With
      Advanced Angiosarcoma: A Randomized Phase II Trial.
AB  - PURPOSE: The aim of this randomized, phase II trial was to explore the activity
      and safety of adding bevacizumab to paclitaxel once per week in treatment of
      angiosarcomas (AS). METHODS: Patients were treated with paclitaxel alone (90
      mg/m(2) per week for six cycles of 28 days each; arm A) or with paclitaxel
      combined with bevacizumab (10 mg/kg once every 2 weeks; arm B). In the
      combination treatment arm, bevacizumab was administered after the six cycles of
      chemotherapy as maintenance therapy (15 mg/kg once every 3 weeks) until
      intolerance or progression occurred. Stratification factors were superficial
      versus visceral AS and de novo versus radiation-induced AS. The primary end point
      was the 6-month progression-free survival (PFS) rate, which was based on RECIST,
      version 1.1. Statistical assumptions were P0 = 20%, P1 = 40%, a = 10%, and b =
      20%. P0 was the PFS rate at 6 months defining inactive drug, and P1 was the PFS
      rate at 6 months defining promising drug. RESULTS: A total of 52 patients were
      enrolled, and 50 were randomly assigned in 14 centers. The most common primary
      sites were the breast (49%) and skin (12%). There were 17 (34%) visceral and 24
      (49%) radiation-induced AS. The performance status was 0 in 24 patients (49%) and
      1 in the remaining 25 patients (51%). The median follow-up time was 14.5 months.
      Both treatment regimens were considered active, with 6-month PFS rates of 54% (14
      of 26) in arm A and 57% (14 of 24) in arm B. The median overall survival rates
      were 19.5 months in arm A and 15.9 months in arm B. Toxicity was higher with the
      combination arm and included one fatal drug-related toxicity (intestinal
      occlusion). CONCLUSION: The primary objective was met in both treatment arms.
      However, the present data do not support additional clinical investigation of
      combined paclitaxel/bevacizumab for the treatment of advanced AS.

PMID- 26215951
TI  - Reply to M.H. Gail et al.

PMID- 26215952
TI  - Next-Generation Sequencing of Pulmonary Sarcomatoid Carcinoma Reveals High
      Frequency of Actionable MET Gene Mutations.
AB  - PURPOSE: To further understand the molecular pathogenesis of pulmonary
      sarcomatoid carcinoma (PSC) and develop new therapeutic strategies in this
      treatment-refractory disease. MATERIALS AND METHODS: Whole-exome sequencing in a
      discovery set (n = 10) as well as targeted MET mutation screening in an
      independent validation set (n = 26) of PSC were performed. Reverse transcriptase
      polymerase chain reaction and Western blotting were performed to validate MET
      exon 14 skipping. Functional studies for validation of the oncogenic roles of MET
      exon 14 skipping were conducted in lung adenosquamous cell line H596 (MET exon 14
      skipped and PIK3CA mutated) and gastric adenocarcinoma cell line Hs746T (MET exon
      14 skipped). Response to MET inhibitor therapy with crizotinib in a patient with
      advanced PSC and MET exon 14 skipping was evaluated to assess clinical
      translatability. RESULTS: In addition to confirming mutations in known cancer
      associated genes (TP53, KRAS, PIK3CA, MET, NOTCH, STK11, and RB1), several novel
      mutations in additional genes, including RASA1, CDH4, CDH7, LAMB4, SCAF1, and
      LMTK2, were identified and validated. MET mutations leading to exon 14 skipping
      were identified in eight (22%) of 36 patient cases; one of these tumors also
      harbored a concurrent PIK3CA mutation. Short interfering RNA silencing of MET and
      MET inhibition with crizotinib showed marked effects on cell viability and
      decrease in downstream AKT and mitogen-activated protein kinase activation in
      Hs746T and H596 cells. Concurrent PIK3CA mutation required addition of a second
      agent for successful pathway suppression and cell viability effect. Dramatic
      response to crizotinib was noted in a patient with advanced chemotherapy
      refractory PSC carrying a MET exon 14 skipping mutation. CONCLUSION: Mutational
      events of MET leading to exon 14 skipping are frequent and potentially targetable
      events in PSC.

PMID- 26215953
TI  - WEE1 Kinase As a Target for Cancer Therapy.

PMID- 26215954
TI  - Reply to K. Lu.

PMID- 26215955
TI  - Reply to G. Gandaglia et al and K. Lu.

PMID- 26215956
TI  - Reply to C. Le Pechoux et al and B.S. Gill et al.

PMID- 26215957
TI  - Human Papillomavirus-Related Oropharyngeal Cancer: Agree With a New Staging
      System, but the Devil Is in the Details.

PMID- 26215958
TI  - Reply to M.H. Kanter et al.

PMID- 26215959
TI  - The Negative Is Not So Negative: What Do We Learn From Trials With Orteronel?

PMID- 26215960
TI  - Caveat for Immortal Time Bias in Adjuvant Therapy-Related Population-Based
      Analyses.

PMID- 26215961
TI  - Reply to J.J. Beitler et al.

PMID- 26215962
TI  - Reply to D.A. Palma et al and A. Addeo et al.

PMID- 26215963
TI  - Urea-Based Cream to Prevent Sorafenib-Induced Hand-and-Foot Skin Reaction: Which
      Evidence?

PMID- 26215964
TI  - Oncolytic Virus-Mediated Immunotherapy: A Combinatorial Approach for Cancer
      Treatment.

PMID- 26215965
TI  - Integration Alone Does Not Reduce Health Care Disparities.

PMID- 26215966
TI  - Cisplatin and Etoposide Versus Carboplatin and Paclitaxel With Concurrent
      Radiation for Stage III Non-Small-Cell Lung Cancer: Is There an Impact on
      Radiation Pneumonitis Rates?

PMID- 26215967
TI  - Older Men With Locally Advanced Prostate Cancer: To Treat or Not to Treat?

PMID- 26215969
TI  - Successful percutaneous coronary intervention with GuideLiner(r) catheter for
      subtotal occlusive lesion in the right coronary artery with anomalous origin from
      the left sinus of Valsalva: a case report.
AB  - INTRODUCTION: Because of the unusual anatomy of an anomalous origin of the right
      coronary artery from the left sinus of Valsalva, selective cannulation of the
      guiding catheter in percutaneous coronary intervention for these cases is always
      challenging. CASE PRESENTATION: A 58-year-old Japanese man was admitted to our
      hospital complaining of worsening exertional chest pain. He was suspected of
      having unstable angina pectoris and underwent cardiac catheterization. We found a
      subtotal occlusive lesion in the mid-portion of his right coronary artery that
      originated from the left sinus of Valsalva. On the previous percutaneous coronary
      intervention, we failed to cannulate the guiding catheter to the anomalous
      orifice of the right coronary artery. Therefore, we decided to use the GuideLiner
      catheter for stable back-up support from the beginning. A 6Fr GuideLiner catheter
      was introduced into the right coronary artery by anchoring it coaxially with a
      semi-compliant balloon catheter. And we successfully deployed two drug-eluting
      stents by crossing over the posterior-descending artery. Final angiography
      demonstrated favorable dilatation of the target lesion, and native blood flow in
      the right coronary artery was completely recovered. CONCLUSION: GuideLiner is a
      monorail-type "child" support catheter that facilitates coaxial guiding catheter
      engagement and an appropriate back-up force, achieving successful device delivery
      to target lesions in this kind of complex percutaneous coronary intervention.

PMID- 26215968
TI  - Phytochrome diversity in green plants and the origin of canonical plant
      phytochromes.
AB  - Phytochromes are red/far-red photoreceptors that play essential roles in diverse
      plant morphogenetic and physiological responses to light. Despite their
      functional significance, phytochrome diversity and evolution across
      photosynthetic eukaryotes remain poorly understood. Using newly available
      transcriptomic and genomic data we show that canonical plant phytochromes
      originated in a common ancestor of streptophytes (charophyte algae and land
      plants). Phytochromes in charophyte algae are structurally diverse, including
      canonical and non-canonical forms, whereas in land plants, phytochrome structure
      is highly conserved. Liverworts, hornworts and Selaginella apparently possess a
      single phytochrome, whereas independent gene duplications occurred within mosses,
      lycopods, ferns and seed plants, leading to diverse phytochrome families in these
      clades. Surprisingly, the phytochrome portions of algal and land plant
      neochromes, a chimera of phytochrome and phototropin, appear to share a common
      origin. Our results reveal novel phytochrome clades and establish the basis for
      understanding phytochrome functional evolution in land plants and their algal
      relatives. 

PMID- 26215970
TI  - microRNA-150: a promising novel biomarker for hepatitis B virus-related
      hepatocellular carcinoma.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection is a known major
      etiological factor for hepatocellular carcinoma (HCC) development. Alpha
      fetoprotein (AFP) is widely used to detect primary HCC, whereas its sensitivity
      and specificity are not satisfying. Recently, circulating microRNAs (miRNAs) have
      been reported to be promising biomarkers for diagnosing and monitoring cancers.
      This study was conducted to detect the application of serum miR-150 in the
      diagnosis and prognosis of HBV-related HCC. METHODS: The expression of miR-150
      was evaluated using a real-time quantitative RT-PCR in 350 serum samples (120
      samples from controls, 110 from chronic hepatitis B (CHB) patients and 120
      samples from HCC patients. RESULTS: Serum miR-150 levels were significantly
      reduced in HCC patients, compared with healthy controls (P < 0.0001) and CHB
      patients (P < 0.0001). Serum miR-150 levels were increased after surgical
      operation (P < 0.0001) and decreased after tumor recurrence (P < 0.0001).
      Receiver operating characteristic curve (ROC) analyses suggested that serum miR
      150 had significant diagnostic value for HBV-related HCC. It yielded an area
      under the curve (AUC) of ROC of 0.931 with 82.5% sensitivity and 83.7%
      specificity in discriminating HCC from healthy controls, and an AUC of ROC of
      0.881 with 79.1% sensitivity and 76.5% specificity in discriminating HCC from CHB
      patients. Moreover, Kaplan-Meier curve analysis revealed that HCC patients with
      lower serum miR-150 had a significantly shortened overall survival (P < 0.0001).
      Univariate and Multivariable Cox regression analysis indicated that serum miR-150
      level was an independent risk factor for overall survival (P < 0.0001 and P =
      0.015, respectively). CONCLUSIONS: Serum miR-150 can serve as a non-invasive
      biomarker for the diagnosis and prognosis of HCC patients.

PMID- 26215971
TI  - IL6 secreted by Ewing sarcoma tumor microenvironment confers anti-apoptotic and
      cell-disseminating paracrine responses in Ewing sarcoma cells.
AB  - BACKGROUND: The prognosis of patients with Ewing sarcoma (ES) has improved over
      the course of the last decades. However, those patients suffering from metastatic
      and recurrent ES still have only poor chances of survival and require new
      therapeutic approaches. Interleukin-6 (IL6) is a pleiotropic cytokine expressed
      by immune cells and a great variety of cancer cells. It induces inflammatory
      responses, enhances proliferation and inhibits apoptosis in cancer cells, thereby
      promoting chemoresistance. METHODS: We investigated expression of IL6, its
      receptors and the IL6 signal transduction pathway in ES tumor samples and cell
      lines applying reverse transcriptase PCR, immunoblot and immunohistochemistry.
      The impact of IL6 on cell viability and apoptosis in ES cell lines was analyzed
      by MTT and propidium iodide staining, migration assessed by chorioallantoic
      membrane (CAM) assay. RESULTS: Immunohistochemistry proved IL6 expression in the
      stroma of ES tumor samples. IL6 receptor subunits IL6R and IL6ST were expressed
      on the surface of ES cells. Treatment of ES cells with rhIL6 resulted in
      phosphorylation of STAT3. rhIL6 protected ES cells from serum starvation-induced
      apoptosis and promoted migration. IL6 blood serum levels were elevated in a
      subgroup of ES patients with poor prognosis. CONCLUSIONS: These data suggest that
      IL6 contributes to ES tumor progression by increasing resistance to apoptosis in
      conditions of cellular stress, such as serum starvation, and by promotion of
      metastasis.

PMID- 26215973
TI  - Seeing What We Build--The Need for New Imaging Techniques in Myocardial
      Regeneration.

PMID- 26215972
TI  - Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of
      Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia
      Reperfusion Model.
AB  - BACKGROUND: The exact mechanism of stem cell therapy in augmenting the function
      of ischemic cardiomyopathy is unclear. In this study, we hypothesized that
      increased viability of the peri-infarct region (PIR) produces restorative
      benefits after stem cell engraftment. A novel multimodality imaging approach
      simultaneously assessed myocardial viability (manganese-enhanced magnetic
      resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI),
      and transplanted stem cell engraftment (positron emission tomography reporter
      gene) in the injured porcine hearts. METHODS AND RESULTS: Twelve adult swine
      underwent ischemia-reperfusion injury. Digital subtraction of MEMRI-negative
      myocardium (intrainfarct region) from delayed gadolinium enhancement MRI-positive
      myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the
      MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem
      cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem
      cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI
      demonstrated an increased PIR viability signal compared with control. Direct PIR
      viability remained higher in hAMSC-treated hearts for >6 weeks. Increased PIR
      viability correlated with improved regional contractility, left ventricular
      ejection fraction, infarct size, and hAMSC engraftment, as confirmed by
      immunocytochemistry. Increased MEMRI and positron emission tomography reporter
      gene signal in the intrainfarct region and the PIR correlated with sustained
      functional augmentation (global and regional) within the hAMSC group (mean
      change, left ventricular ejection fraction: hAMSC 85+/-60%, control 8+/-10%;
      P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume
      increase: hAMSC 24+/-8%, control 110+/-30%; P<0.05). CONCLUSIONS: The positron
      emission tomography reporter gene signal of hAMSC engraftment correlates with the
      improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR
      viability and the restorative potential of the injured heart. This in vivo
      multimodality imaging platform represents a novel, real-time method of tracking
      PIR viability and stem cell engraftment while providing a mechanistic explanation
      of the therapeutic efficacy of cardiovascular stem cells.

PMID- 26215974
TI  - Exploring the Relationship Between Professional Commitment and Job Satisfaction
      Among Nurses.
AB  - This cross-sectional study explored the relationship between professional
      commitment and job satisfaction among nurses. A total of 132 registered nurses
      were recruited from a hospital in northern Taiwan. A self-reported structured
      questionnaire was used to collect data. Findings revealed significant differences
      among nurses in willingness to make an effort and their marital status, appraisal
      in continuing their careers, job level, and goals and values related to working
      shifts. Significant differences were found between inner satisfaction and work
      sector and marital status. Nurses' professional commitment was strongly related
      to job satisfaction; aspects of professional commitment explained 32% of the
      variance in job satisfaction. Study results may inform health care institutions
      about the importance of nurses' job satisfaction and professional commitment so
      hospital administration can improve these aspects of organizational environment. 

PMID- 26215975
TI  - Walkability Audit Tool.
AB  - Walking is one of the simplest lifestyle changes workers can make to improve
      their health. Research shows a wealth of health benefits. Often, occupational and
      environmental health nurses are in charge of implementing walking programs. A
      tool is needed to continuously improve a company's walking program whether in the
      beginning stages or to an already established program. The Centers for Disease
      Control and Prevention (CDC) Walkability Audit Tool for a healthier worksite is
      an easy seven-step audit tool that occupational and environmental health nurses
      can easily implement. 

PMID- 26215976
TI  - Creating the Nurses' Environmental Awareness Tool (NEAT).
AB  - Acute care delivery creates secondary health risks to patients, health care
      workers, and the environment through a complex waste stream, intensive energy
      use, and frequent use of harmful chemicals. Nurses are among the most affected by
      these risks and are also pivotal change agents in reducing the negative impacts
      of health care delivery. Assessing nurses' understanding of health care
      associated environmental health risks is essential if care is to be delivered in
      an environmentally safe and healthy manner, as indicated by published
      professional standards of nursing practice. However, psychometrically sound
      instruments that measure nurses' awareness of the environmental impacts of
      nursing practice are not available. To address this gap, a prototype of the
      Nurse's Environmental Awareness Tool (NEAT) was developed. Seven content experts
      in environmental health nursing and/or psychometrics were asked to review draft
      items. Comments were analyzed and applied to the scale items. Several revisions
      from the original item pool were made. The resulting draft NEAT includes six
      subscales, in three paired subsets. This article provides a summary of the
      process of item development and scale design. These findings, although
      preliminary, provide a foundation for subsequent psychometric testing. The result
      of this study is the creation of an instrument to measure nurses' awareness of
      and behaviors associated with the environmental impact of their practices. 

PMID- 26215977
TI  - Sexual disinhibition and dementia.
AB  - To describe inappropriate sexual behaviour (ISB) observed in patients with
      dementia, we conducted searches using the Cochrane Library, PubMed, and Web of
      Science to find relevant articles, chapters, and books published from 1950 to
      2014. Search terms used included 'hypersexuality', 'inappropriate sexual
      behaviors', and 'dementia'. Publications found through this indexed search were
      reviewed for further relevant references. Sexuality is a human's need to express
      intimacy, but persons with dementia may not know how to appropriately meet their
      needs for closeness and intimacy due to their decline in cognition. Generally,
      the interaction among brain, physical, psychological, and environmental factors
      can create what we call ISB. The most likely change in the sexual behaviour of a
      person with dementia is indifference. However, ISB in dementia appear to be of
      two types--intimacy-seeking and disinhibited--that differ in their association
      with dementia type, dementia severity and, possibly, other concurrent behavioural
      disorder. Tensions develop from uncertainties regarding which, or when,
      behaviours are to be considered 'inappropriate' (i.e. improper) or abnormal.
      While most ISB occur in the moderate to severe stages of Alzheimer's dementia,
      they may also be seen in early stages of frontotemporal dementia because of the
      lack of insight and disinhibition. ISB are often better managed by non
      pharmacological means, as patients may be less responsive to psychoactive
      therapies, but non-pharmacological interventions do not always stop the
      behaviour.

PMID- 26215978
TI  - Patterns of health-related quality of life and associated factors in Chinese
      patients undergoing haemodialysis.
AB  - BACKGROUND: Haemodialysis (HD) is a life-saving but burdensome therapy for
      patients with end-stage renal disease (ESRD) which can have a detrimental impact
      on patients' quality of life and outcomes. There is currently little data on the
      health related quality of life (HRQOL) of Chinese ESRD patients undergoing HD and
      this study sought to examine the patterns of HRQOL and its associated factors
      within this population, as well as in comparison with the general local
      population. METHODS: A cross-sectional study of 244 ESRD patients receiving HD in
      the hospital and in the community in Hong Kong was conducted using the Short Form
      12 Health Survey version 2 (SF-12v2). All study subjects were one-to-one matched
      with subjects in a Hong Kong general population database by sex and exact age.
      Independent t-tests were performed to compare the mean SF-12v2 scores between HD
      patients and the general population, followed by one-way analysis of variance
      with post hoc Tukey's HSD tests to compare community-based haemodialysis,
      hospital-based haemodialysis and the general population. Multiple linear
      regressions were used to identify the factors (socio-demographic, clinical
      characteristics and comorbidities) associated with the HRQOL scores of ESRD
      patients receiving HD. RESULTS: The SF-12v2 Physical Functioning, Role Physical,
      Bodily Pain, General Health and Physical Component Summary scores of HD patients
      were significantly lower than the age-sex adjusted general population. However,
      the SF-12v2 Mental Health and Mental Component Summary scores of HD patients were
      significantly higher than the corresponding general population. Poorer HRQOL was
      associated with being female, smoking, unemployment and hospital-based
      haemodialysis. CONCLUSIONS: HD patients had substantially poorer physical HRQOL
      but better mental HRQOL than the age-sex adjusted general population. Patients
      receiving HD in the community setting had better HRQOL. Reasons for these
      observations will need to be further investigated. Those patients who are female,
      smokers and unemployed may warrant more attention as their poorer HRQOL may be
      associated with poorer outcomes.

PMID- 26215979
TI  - Inbound medical tourism to Barbados: a qualitative examination of local lawyers'
      prospective legal and regulatory concerns.
AB  - BACKGROUND: Enabled by globalizing processes such as trade liberalization,
      medical tourism is a practice that involves patients' intentional travel to
      privately obtain medical care in another country. Empirical legal research on
      this issue is limited and seldom based on the perspectives of destination
      countries receiving medical tourists. We consulted with diverse lawyers from
      across Barbados to explore their views on the prospective legal and regulatory
      implications of the developing medical tourism industry in the country. METHODS:
      We held a focus group in February 2014 in Barbados with lawyers from across the
      country. Nine lawyers with diverse legal backgrounds participated. Focus group
      moderators summarized the study objective and engaged participants in identifying
      the local implications of medical tourism and the anticipated legal and
      regulatory concerns. The focus group was transcribed verbatim and analyzed
      thematically. RESULTS: Five dominant legal and regulatory themes were identified
      through analysis: (1) liability; (2) immigration law; (3) physician licensing;
      (4) corporate ownership; and (5) reputational protection. CONCLUSIONS: Two
      predominant legal and ethical concerns associated with medical tourism in
      Barbados were raised by participants and are reflected in the literature: the
      ability of medical tourists to recover medical malpractice for adverse events;
      and the effects of medical tourism on access to health care in the destination
      country. However, the participants also identified several topics that have
      received much less attention in the legal and ethical literature. Overall this
      analysis reveals that lawyers, at least in Barbados, have an important role to
      play in the medical tourism sector beyond litigation - particularly in
      transactional and gatekeeper capacities. It remains to be seen whether these
      findings are specific to the ecology of Barbados or can be extrapolated to the
      legal climate of other medical tourism destination countries.

PMID- 26215980
TI  - Internal migration and the health of the returned population: a nationally
      representative study of China.
AB  - BACKGROUND: China had 236 million internal migrants in 2012 and the majority of
      them migrated from rural to urban areas. The research based on medical and
      epidemical records found that the migrants had worse health than the urban
      residents, but the household and working place investigations reported better
      health status. The sick or unhealthy migrants are likely to return to their
      hometowns, which in turn may cause a report bias or over-estimation of the health
      status of rural-to-urban migrants in China. This paper explores the association
      of migration status and the physical and psychological health of Chinese internal
      migrants. METHODS: Nationally representative household survey data from the China
      Labor-force Dynamics Survey 2012 (CLDS) were used to analyze the association
      between the migration status and the health status of internal migrants in China.
      Migration status of the respondents was measured by hukou status and migration
      experience and all respondents were divided into four groups: returned
      population, migrant population, urban residents, and rural residents. Health
      status of respondents was measured by self-reported physical and psychological
      health. RESULTS: Migration experience was associated with the physical health of
      the returned population. The physical health of the returned population was worse
      than the migrant population and was distinguished by age and sex. The physical
      health status of migrant population was significantly better than rural
      residents, but not significantly better than urban residents. However, the
      association between migration status and psychological health was not
      statistically significant. Besides migration status, the socioeconomic status
      (SES) had a positive correlation with both physical and psychological health
      status, while occupational hazards exerted negative influence. CONCLUSION: The
      results indicate a tight association between migration experience and health
      status. The internal unhealthy migrants were more likely to return to their
      hometown and the migrant population might have limited health advantage.

PMID- 26215982
TI  - State of the art in germ cell tumor imaging.
AB  - Germ cell tumors (GCTs) are the most common tumors of the testis and arise from
      germinal epithelium cells in the seminiferous tubules. All GCTs show malignant
      behavior and frequently metastasize. The diagnosis of GCTs depends on the
      clinical manifestations, laboratory parameters, preoperative imaging features,
      and tissue biomarkers. Ultrasonography and Doppler ultrasonography are the
      primary imaging modalities used to evaluate testicular masses. Sonoelastography
      is a diagnostic tool that can measure the stiffness of tissue and may
      differentiate between benign and malignant tumors of testis. Magnetic resonance
      imaging of the scrotum may be used as an additional tool, which may provide
      additional information owing to its high soft tissue contrast discrimination
      capability. Computed tomography of the thorax and abdomen and positron emission
      tomography/computed tomography are used for staging of the disease and for follow
      up after treatment. 

PMID- 26215981
TI  - Early hyperlactatemia predicts pancreatic fistula after surgery.
AB  - BACKGROUND: Postoperative pancreatic fistula (POPF) is a major complication after
      pancreatic surgery and results from an impaired healing of the pancreatic enteric
      anastomosis. Whether perioperative hemodynamic fluid management aiming to provide
      an adequate tissue perfusion could influence the occurrence of POPF is unknown.
      Serum lactate level is a well-recognized marker of decreased tissue perfusion and
      is known to be associated with higher morbidity and mortality in various
      postoperative settings. We aimed to determine in a retrospective high-volume
      center's cohort whether postoperative hyperlactatemia could predict POPF
      occurrence. METHOD: We conducted a retrospective analysis of 96 consecutive
      patients admitted in the intensive care unit (ICU) after pancreaticoduodenectomy
      or distal pancreatectomy. Univariate analysis was conducted to compare lactate
      levels at 6 h between patients evolving with versus without POPF. A logistic
      regression model was developed and included potential confounding factors.
      RESULTS: POPF occurred in 28 patients (29 %). Serum lactate level 6 h after
      admission was significantly higher in the POPF group (2.8 mmol/L [95 % confidence
      interval (CI): 2.1-3.5] versus 1.8 mmol/L [95 % CI: 1.8-2.4], p-value = 0.04)
      whereas it did not differ at ICU admission or at 12 h. Despite similar cumulative
      fluid balance, fluid intake and vasopressor use, hyperlactatemia > 2.5 mmol/L
      (Odds ratio (OR): 3.58; 95 % CI: 1.22-10.48; p-value = 0.020) and red blood cells
      transfusion (OR: 1.24; 95 % CI: 1.03-1.49; p-value = 0.022) were found to be
      independent predictive factors of POPF occurrence. CONCLUSION: In patients
      undergoing partial pancreatectomy, hyperlactatemia measured 6 h after ICU
      admission is a predictive factor for the occurrence of POPF. Inflammatory changes
      after surgery may account for this observation and should be further evaluated.

PMID- 26215983
TI  - Clustered data analysis under miscategorized ordinal outcomes and missing
      covariates.
AB  - The primary objective in this article is to look into the analysis of clustered
      ordinal model where complete information on one or more covariates cease to
      occur. In addition, we also focus on the analysis of miscategorized data that
      occur in many situations as outcomes are often classified into a category that
      does not truly reflect its actual state. A general model structure is assumed to
      accommodate the information that is obtained via surrogate variables. The
      theoretical motivation actually developed while encountering an orthodontic data
      to investigate the effects of age, sex and food habit on the extent of plaque
      deposit. The model we propose is quite flexible and is capable of tackling those
      additional noises like miscategorization and missingness, which occur in the data
      most frequently. A new two-step approach has been proposed to estimate the
      parameters of model framed. A rigorous simulation study has also been carried out
      to justify the validity of the model taken up for analysis. Copyright (c) 2015
      John Wiley & Sons, Ltd.

PMID- 26215985
TI  - Out-of-hospital cardiac arrest: contemporary management and future perspectives.

PMID- 26215984
TI  - ANISERP: a new serpin from the parasite Anisakis simplex.
AB  - BACKGROUND: Serine proteinase inhibitors (serpins) finely regulate serine
      proteinase activity via a suicide substrate-like inhibitory mechanism. In
      parasitic nematodes, some serpins interact with host physiological processes;
      however, little is known about these essential molecules in Anisakis. This
      article reports the gene sequencing, cloning, expression and preliminary
      biochemical and bioinformatically-based structural characterization of a new
      Anisakis serpin (ANISERP). METHODS: The full AniSerp gene was cloned by specific
      RACE-PCR after screening an Anisakis simplex (L3) cDNA library. For biochemical
      assays, the AniSerp gene was subcloned into both prokaryotic and eukaryotic
      vectors, and the recombinant proteins were purified. The inhibitory properties of
      the proteins were tested in classical biochemical assays using human serine
      peptidases and AMC substrates. Immunolocalization of ANISERP, theoretical
      structural analysis and bioinformatically-based structural modelling of the
      ANISERP protein were also conducted. RESULTS: The AniSerp gene was found to have
      1194 nucleotides, coding for a protein of 397 amino acid residues plus a putative
      N-terminal signal peptide. It showed significant similarity to other nematode,
      arthropod and mammalian serpins. The recombinant ANISERP expressed in the
      prokaryotic and eukaryotic systems inhibited the human serine proteases thrombin,
      trypsin and cathepsin G in a concentration-dependent manner. No inhibitory
      activity against Factor Xa, Factor XIa, Factor XIIa, elastase, plasmin or
      chymotrypsin was observed. ANISERP also acted on the cysteine protease cathepsin
      L. ANISERP was mainly localized in the nematode pseudocoelomic fluid, somatic
      muscle cell bodies and intestinal cells. The findings of molecular dynamics
      studies suggest that ANISERP inhibits thrombin via a suicide substrate-like
      inhibitory mechanism, similar to the mechanism of action of mammalian coagulation
      inhibitors. In contrast to findings concerning human antithrombin III, heparin
      had no effect on ANISERP anticoagulant inhibitory activity. CONCLUSIONS: Our
      findings suggest that ANISERP is an internal Anisakis regulatory serpin and that
      the inhibitory activity against thrombin depends on a suicide substrate-like
      inhibitory mechanism, similar to that described for human antithrombin (AT)-III.
      The fact that heparin does not modulate the anticoagulant activity of ANISERP
      might be explained by the absence in the latter of five of the six positively
      charged residues usually seen at the AT-III-heparin binding site.

PMID- 26215986
TI  - Cystatin C as a predictive marker of renal dysfunction and mid-term outcomes
      following off-pump coronary artery bypass grafting.
AB  - OBJECTIVE: To determine whether plasma cystatin C and creatinine levels after
      isolated off-pump coronary artery bypass grafting (OPCAB) are predictive of
      postoperative renal dysfunction and clinical outcomes. METHODS: Between January
      2008 and December 2013, 1033 who underwent isolated OPCAB were recruited. The
      patients were divided into three groups according to the preoperative level of
      cystatin C: low (0.83 mg/L>), mid (0.83-1.13 mg/L) and high (1.13 mg/L<). The
      endpoints of all-cause mortality and major adverse cerebrovascular and
      cardiovascular events were compared among three groups using the Kaplan-Meier
      method. The predictive power of cystatin C was compared with creatinine using
      receiver operating curves. RESULTS: Follow-up was complete in all of the included
      patients at a mean of 2.9+/-1.5 years. Within the follow-up period, 9 early (30
      day mortality) and 46 late deaths occurred. The 30-day mortality was zero, four
      (44%), and five (56%) cases in low, mid and high groups, respectively (p=0.03).
      The cut-off value of cystatin C for renal dysfunction prediction was
      approximately 1.04 (mg/L, p<0.001), and cystatin C showed greater predictive
      power than creatinine for renal dysfunction (area under the curve=0.73 vs 0.65;
      p=0.01). One-year and five-year overall survival in low, mid and high groups were
      99.2%, 98.9% and 94.3%, and 97.9%, 97.3% and 86.3%, respectively (low vs high,
      p=0.01). CONCLUSIONS: Cystatin C is a stronger predictor of postoperative renal
      dysfunction than serum creatinine, and its level is directly correlated with mid
      term OPCAB adverse results.

PMID- 26215987
TI  - What the Cardiologist Should Know About Cardiac Involvement in Behcet Disease.
AB  - Behcet disease (BD) is a chronic multisystem inflammatory vasculitis affecting
      mainly young adults and is characterized by a remitting-relapsing course. In
      North America, the prevalence is 5.2 per 100,000 population. It is believed that
      cardiac involvement is one of the most severe complications in patients with BD
      despite its sporadic occurrence, being greatly correlated with mortality. 

PMID- 26215988
TI  - Regulatory Actions of Glucocorticoid Hormones: From Organisms to Mechanisms.
AB  - The history of glucocorticoid hormone research is an excellent example of
      "bedside to bench" investigation. It started with two very insightful clinical
      observations. Thomas Addison described the syndrome of what came to be known as
      adrenal hormone insufficiency and Harvey Cushing the syndrome of glucocorticoid
      hormone excess. These dramatic and life-threatening conditions spawned 150 years
      of active research that has involved many disciplines; indeed some of the
      fundamental observations of molecular biology are the result of this work. We
      have a fundamental knowledge of how glucocorticoids regulate gene transcription,
      their major effect. The challenge facing current and future investigators is to
      discern how to use this information to make these powerful therapeutic agents
      safer and more effective. 

PMID- 26215989
TI  - Molecular Biology of Glucocorticoid Signaling.
AB  - Well-defined as signaling hormones for the programming of cell type-specific and
      context-dependent gene expression signatures, glucocorticoids control experience
      driven allostasis. One unifying model is that glucocorticoids help maintaining
      the integrity and plasticity of cellular networks in changing environments
      through the mobilization of cellular energy stores, profiling of gene expression,
      and changes in the electrical and morphological properties of cells. The nucleus
      is their primary site of action, yet recent discoveries point to additional gene
      transcription-independent functions at the plasma membrane of neuronal synapses.
      Glucocorticoids are secreted factors that reflect intrinsically the changes
      coming from the external world, temporally and regionally, during development and
      adulthood. In this review, we will enumerate the properties and signaling
      attributes of glucocorticoids and their receptors that characterize them as
      allostatic modulators. The molecular mechanisms used to support their role at the
      synapse will be highlighted. 

PMID- 26215990
TI  - Mechanisms of Glucocorticoid-Regulated Gene Transcription.
AB  - One fascinating aspect of glucocorticoid signaling is their broad range of
      physiological and pharmacological effects. These effects are at least in part a
      consequence of transcriptional regulation by the glucocorticoid receptor (GR).
      Activation of GR by glucocorticoids results in tissue-specific changes in gene
      expression levels with some genes being activated whereas others are repressed.
      This raises two questions: First, how does GR regulate different subsets of
      target genes in different tissues? And second, how can GR both activate and
      repress the expression of genes?To answer these questions, this chapter will
      describe the function of the various "components" and how they cooperate to
      mediate the transcriptional responses to glucocorticoids. The first "component"
      is GR itself. The second "component" is the chromatin and its role in specifying
      where in the genome GR binds. Binding to the genome however is just the first
      step in regulating the expression of genes and transcriptional regulation by GR
      depends on the recruitment of coregulator proteins that either directly or
      indirectly influence the recruitment and or activity of RNA polymerase II.
      Ultimately, the integration of inputs including GR isoform, DNA sequence,
      chromatin and cooperation with coregulators determines which genes are regulated
      and the direction of their regulation. 

PMID- 26215991
TI  - Clinical Perspective: What Do Addison and Cushing Tell Us About Glucocorticoid
      Action?
AB  - This chapter is distinct from the others in its clinical subject matter. I will
      attempt to outline the major points of interest in glucocorticoids clinically. To
      aid the illustration in the evaluation of a patient with Cushing disease I have
      created a case study. 

PMID- 26215993
TI  - How Do Glucocorticoids Regulate Lipid Metabolism?
AB  - Glucocorticoids (GCs) and their cognate, intracellular receptor, the
      glucocorticoid receptor (GR) have been characterized as critical checkpoints in
      the hormonal control of energy homeostasis in mammals. Whereas physiological
      levels of GCs are required for proper metabolic control, aberrant GC action has
      been linked to a variety of severe metabolic diseases, including type 2 diabetes
      and obesity. As a member of the nuclear receptor superfamily of transcription
      factors, the GR translocates into the cell nucleus upon GC binding where it
      serves as a transcriptional regulator of distinct GC-responsive target genes that
      are in many cases associated with lipid regulatory pathways and thereby
      intricately control both physiological and pathophysiological systemic lipid
      homeostasis. Thus, this chapter focuses on the current knowledge of GC/GR
      function in lipid handling and its implications for systemic metabolic
      dysfunction. 

PMID- 26215994
TI  - Glucocorticoids and Skeletal Muscle.
AB  - Glucocorticoids are known to regulate protein metabolism in skeletal muscle,
      producing a catabolic effect that is opposite that of insulin. In many catabolic
      diseases, such as sepsis, starvation, and cancer cachexia, endogenous
      glucocorticoids are elevated contributing to the loss of muscle mass and
      function. Further, exogenous glucocorticoids are often given acutely and
      chronically to treat inflammatory conditions such as asthma, chronic obstructive
      pulmonary disease, and rheumatoid arthritis, resulting in muscle atrophy. This
      chapter will detail the nature of glucocorticoid-induced muscle atrophy and
      discuss the mechanisms thought to be responsible for the catabolic effects of
      glucocorticoids on muscle. 

PMID- 26215992
TI  - Regulation of Glucose Homeostasis by Glucocorticoids.
AB  - Glucocorticoids are steroid hormones that regulate multiple aspects of glucose
      homeostasis. Glucocorticoids promote gluconeogenesis in liver, whereas in
      skeletal muscle and white adipose tissue they decrease glucose uptake and
      utilization by antagonizing insulin response. Therefore, excess glucocorticoid
      exposure causes hyperglycemia and insulin resistance. Glucocorticoids also
      regulate glycogen metabolism. In liver, glucocorticoids increase glycogen
      storage, whereas in skeletal muscle they play a permissive role for catecholamine
      induced glycogenolysis and/or inhibit insulin-stimulated glycogen synthesis.
      Moreover, glucocorticoids modulate the function of pancreatic alpha and beta
      cells to regulate the secretion of glucagon and insulin, two hormones that play a
      pivotal role in the regulation of blood glucose levels. Overall, the major
      glucocorticoid effect on glucose homeostasis is to preserve plasma glucose for
      brain during stress, as transiently raising blood glucose is important to promote
      maximal brain function. In this chapter we will discuss the current understanding
      of the mechanisms underlying different aspects of glucocorticoid-regulated
      mammalian glucose homeostasis. 

PMID- 26215996
TI  - Effects of Glucocorticoids in the Immune System.
AB  - Glucocorticoids (GCs) are steroid hormones with widespread effects. They control
      intermediate metabolism by stimulating gluconeogenesis in the liver, mobilize
      amino acids from extra hepatic tissues, inhibit glucose uptake in muscle and
      adipose tissue, and stimulate fat breakdown in adipose tissue. They also mediate
      stress response. They exert potent immune-suppressive and anti-inflammatory
      effects particularly when administered pharmacologically. Understanding these
      diverse effects of glucocorticoids requires a detailed knowledge of their mode of
      action. Research over the years has uncovered several details on the molecular
      action of this hormone, especially in immune cells. In this chapter, we have
      summarized the latest findings on the action of glucocorticoids in immune cells
      with a view of identifying important control points that may be relevant in
      glucocorticoid therapy. 

PMID- 26215997
TI  - Glucocorticoids and the Brain: Neural Mechanisms Regulating the Stress Response.
AB  - In this chapter, we describe the central role of the brain in the glucocorticoid
      mediated stress response. We describe the mechanisms by which the brain gauges
      the severity of stress, mechanisms of hypothalamic-pituitary-adrenal axis (HPA)
      regulation, and how various sub-systems of the brain respond to glucocorticoid
      (GC) signaling to regulate stress behavior. In particular, we focus on the
      hippocampus, pre-frontal cortex, and amygdala, where GCs can induce a series of
      changes. Finally, we briefly discuss an apparent paradox in GC signaling: while
      exposure to glucocorticoids promotes the survival of an organism during acute
      stress, these same hormones in chronic excess can also cause damage and promote
      illness. 

PMID- 26215998
TI  - Glucocorticoid Regulation of Reproduction.
AB  - It is well accepted that stress, measured by increased glucocorticoid secretion,
      leads to profound reproductive dysfunction. In times of stress, glucocorticoids
      activate many parts of the fight or flight response, mobilizing energy and
      enhancing survival, while inhibiting metabolic processes that are not necessary
      for survival in the moment. This includes reproduction, an energetically costly
      procedure that is very finely regulated. In the short term, this is meant to be
      beneficial, so that the organism does not waste precious energy needed for
      survival. However, long-term inhibition can lead to persistent reproductive
      dysfunction, even if no longer stressed. This response is mediated by the
      increased levels of circulating glucocorticoids, which orchestrate complex
      inhibition of the entire reproductive axis. Stress and glucocorticoids exhibits
      both central and peripheral inhibition of the reproductive hormonal axis. While
      this has long been recognized as an issue, understanding the complex signaling
      mechanism behind this inhibition remains somewhat of a mystery. What makes this
      especially difficult is attempting to differentiate the many parts of both of
      these hormonal axes, and new neuropeptide discoveries in the last decade in the
      reproductive field have added even more complexity to an already complicated
      system. Glucocorticoids (GCs) and other hormones within the hypothalamic
      pituitary-adrenal (HPA) axis (as well as contributors in the sympathetic system)
      can modulate the hypothalamic-pituitary-gonadal (HPG) axis at all levels-GCs can
      inhibit release of GnRH from the hypothalamus, inhibit gonadotropin synthesis and
      release in the pituitary, and inhibit testosterone synthesis and release from the
      gonads, while also influencing gametogenesis and sexual behavior. This chapter is
      not an exhaustive review of all the known literature, however is aimed at giving
      a brief look at both the central and peripheral effects of glucocorticoids on the
      reproductive function. 

PMID- 26215999
TI  - Glucocorticoids and the Lung.
AB  - The lung is a major clinical target of glucocorticoid-based therapeutics, and GR
      signaling has broad effects on respiratory physiology and inflammation. During
      lung development, expression of GR in the mesenchyme is required for normal
      terminal alveolar epithelial differentiation. Prenatal administration of
      exogenous glucocorticoids (GCs) to prevent neonatal respiratory distress
      syndrome, however, promotes alveolar maturation and accelerates surfactant
      expression in a manner consistent with direct effects on the developing alveolar
      epithelium. Likewise, cell autonomous effects of GCs in regulating gene
      expression and phenotype of the airway epithelium and airway smooth muscle have
      been demonstrated to control important therapeutic effects of GCs in treating
      asthma and chronic obstructive pulmonary disease. Here, mechanisms and
      consequences of GR signaling in the developing lung and in treating obstructive
      lung disease are reviewed, with a focus on direct effects of GR signaling on
      alveolar differentiation, surfactant expression, and airway epithelial and smooth
      muscle pathophysiology. 

PMID- 26215995
TI  - Glucocorticoid-Induced Osteoporosis.
AB  - Osteoporosis is among the most devastating side effects of glucocorticoid (GC)
      therapy for the management of inflammatory and auto-immune diseases. Evidence
      from both humans and mice indicate deleterious skeletal effects within weeks of
      pharmacological GC administration, both related and unrelated to a decrease in
      bone mineral density (BMD). Osteoclast numbers and bone resorption are also
      rapidly increased, and together with osteoblast inactivation and decreased bone
      formation, these changes lead the fastest loss in BMD during the initial disease
      phase. Bone resorption then decreases to sub-physiological levels, but persistent
      and severe inhibition of bone formation leads to further bone loss and
      progressively increased fracture risk, up to an order of magnitude higher than
      that observed in untreated individuals. Bone forming osteoblasts are thus
      considered the main culprits in GC-induced osteoporosis (GIO). Accordingly, we
      focus this review primarily on deleterious effects on osteoblasts: inhibition of
      cell replication and function and acceleration of apoptosis. Mediating these
      adverse effects, GCs target pivotal regulatory mechanisms that govern osteoblast
      growth, differentiation and survival. Specifically, GCs inhibit growth factor
      pathways, including Insulin Growth Factors, Growth Hormone, Hepatocyte
      Growth/Scatter Factor and IL6-type cytokines. They also inhibit downstream
      kinases, including PI3-kinase and the MAP kinase ERK, the latter attributable in
      part to direct transcriptional stimulation of MAP kinase phosphatase 1. Most
      importantly, however, GCs inhibit the Wnt signaling pathway, which plays a
      pivotal role in osteoblast replication, function and survival. They
      transcriptionally stimulate expression of Wnt inhibitors of both the Dkk and Sfrp
      families, and they induce reactive oxygen species (ROS), which result in loss of
      beta-catenin to ROS-activated FoxO transcription factors. Identification of
      dissociated GCs, which would suppress the immune system without causing
      osteoporosis, is proving more challenging than initially thought, and GIO is
      currently managed by co-treatment with bisphosphonates or PTH. These drugs,
      however, are not ideally suited for GIO. Future therapeutic approaches may aim at
      GC targets such as those mentioned above, or newly identified targets including
      the Notch pathway, the AP-1/Il11 axis and the osteoblast master regulator RUNX2. 

PMID- 26216000
TI  - Glucocorticoids and the Cardiovascular System.
AB  - Glucocorticoids affect the developing and mature cardiovascular system in
      profound and, at times, contradictory ways. The glucocorticoid receptor is
      ubiquitous in most cell types and conserved across species, highlighting its
      importance in development and homeostasis. Despite the fact that the
      glucocorticoid receptor is widely expressed, tissue-specific effects of
      glucocorticoids may have pronounced effects on whole organism phenotypes. Here we
      will review the interactions between glucocorticoids and the cardiovascular
      system. 

PMID- 26216002
TI  - Animal Models of Altered Glucocorticoid Signaling.
AB  - In this chapter we will review genetically engineered mice with alterations in
      glucocorticoid signaling. Most of the mice involve direct alterations to the
      glucocorticoid receptor locus, but we will touch briefly on other relevant models
      including 11-beta-HSD transgenics which alter tissue levels of ligand as well as
      mice with glucocorticoid excess. Of course, the number of mice with mutations in
      genes such as GR targets and transcriptional coregulators is beyond the scope of
      this chapter. 

PMID- 26216003
TI  - The Dehydrogenase Hypothesis.
AB  - Circulating glucocorticoid (GC) levels are controlled by the Hypothalamo
      Pituitary-Adrenal (HPA) axis, but within tissues, GC availability is controlled
      by the isoforms of 11beta (Beta)-Hydroxysteroid Dehydrogenase 11beta (Beta)-HSD
      that interconvert inactive cortisone and active cortisol. Two isoforms have been
      identified; in key metabolic target tissues (including liver and adipose),
      expression of 11beta (Beta)-HSD1 predominates that in vivo converts cortisone to
      cortisol and thus amplifies local GC action. In contrast, in mineralocorticoid
      target tissues 11beta (Beta)-HSD2 is the isoform that is most abundantly
      expressed. This inactivates cortisol to cortisone and offers protection for the
      mineralocorticoid receptor form occupation and activation by cortisol.
      Dysregulated 11beta (Beta)-HSD1 activity has been implicated in many metabolic
      diseases such as obesity and diabetes and inhibition of 11beta (Beta)-HSD1
      represents a promising therapeutic target. Mutations within the gene encoding
      11beta (Beta)-HSD2 cause the Syndrome of Apparent Mineralocorticoid Excess and
      decreases in activity are linked to hypertension as well as impairment in
      placental function and neonatal growth. We will discuss the molecular biology and
      enzymology of 11beta (Beta)-HSD and its role in normal physiology and discuss
      altered 11beta (Beta)-HSD activity in pathological states and the potential for
      therapeutic targeting. 

PMID- 26216001
TI  - Glucocorticoids and Cancer.
AB  - Unlike other steroid hormone receptors, the glucocorticoid receptor (GR) is not
      considered an oncogene. In breast cancer, the estrogen receptor (ER) drives cell
      growth, proliferation, and metastasis, and the androgen receptor (AR) plays a
      similar role in prostate cancer. Accordingly, treatment of these diseases has
      focused on blocking steroid hormone receptor function. In contrast,
      glucocorticoids (GCs) work through GR to arrest growth and induce apoptosis in
      lymphoid tissue. Glucocorticoids are amazingly effective in this role, and have
      been deployed as the cornerstone of lymphoid cancer treatment for decades.
      Unfortunately, not all patients respond to GCs and dosage is restricted by
      immediate and long term side effects. In this chapter we review the treatment
      protocols that employ glucocorticoids as a curative agent, elaborate on what is
      known about their mechanism of action in these cancers, and also summarize the
      palliative uses of glucocorticoids for other cancers. 

PMID- 26216004
TI  - Conclusions and Future Directions.
AB  - We hope this book has provided a robust introduction to glucocorticoid action. We
      have provided a historical perspective on discoveries related to glucocorticoid
      action: from the discovery of the hormones, their use as therapeutics for
      inflammatory disease, biochemical identification of receptors and finally the
      cloning of the glucocorticoid receptor. This has led to identification of not
      only the primary amino acid sequence, but structural information gleaned from
      both X-ray crystallography as well as nuclear magnetic resonance approaches. We
      hope the reader comes away with a better understanding of the many actions of
      glucocorticoids on various tissues and cell types. Indeed, one of the unanswered
      questions in our field is how one hormone and receptor can have such varied
      transcriptional responses in different cell types. Surely, some of this will be
      explained by epigenetic modifications that occur in different cell types. 

PMID- 26216005
TI  - Nurse migration from India: a literature review.
AB  - BACKGROUND: A profound nursing shortage exists in India where nurses are
      increasingly outmigrating to practice nursing in surrounding countries and
      abroad. This is important globally because countries with the lowest nursing and
      healthcare workforce capacities have the poorest health outcomes. OBJECTIVE: This
      review sought to synthesize and unify the evidence about nurse migration from
      India and includes a look at nurse retention within India. DESIGN: A
      comprehensive literature review was performed to synthesize and unify both
      qualitative and quantitative research. DATA SOURCES: Bibliographic databases
      searched included CINAHL, MEDLINE, PsycINFO, and EconLit using associated
      keywords for empirical and descriptive literature published between January 2004
      and May 2014. Hand searches of the Nursing Journal of India from 2004 to February
      2014 and the Journal of Nursing Research Society of India from its inception in
      2007-February 2014 were also completed. REVIEW PROCESS: 29 studies were selected
      and analyzed for the review. Data were appraised for quality; reduced through sub
      categorization; extracted; and coded into a framework. Thematic interpretation
      occurred through comparing and contrasting performed by multiple reviewers.
      RESULTS: Findings included an exponential growth in nurse recruitment efforts,
      nurse migration, and a concomitant growth in educational institutions within
      India with regional variations in nurse migration patterns. Decision-making
      factors for migration were based on working conditions, salience of family, and
      the desire for knowledge, skill, technology, adventure and personal enrichment.
      Challenges associated with migration included questionable recruiting practices,
      differing scopes of practice encountered after migration and experiences of
      racism and cultural differences. A shift toward a positive transformation of
      nursing status in India has resulted in an increased respect for individual
      nurses and the profession of nursing. This was attributed to the increased
      globalization of nursing. CONCLUSIONS: Results from this review can be used to
      shape health policy and advocate for nursing reform in India. As India's
      healthcare infrastructure continues to evolve, effective programs to improve
      conditions for nurses and retain them in India are needed. Additionally, as the
      globalization of nurses increases, more research is needed to develop effective
      programs to aid in a smooth transition for nurses who migrate from India.

PMID- 26216006
TI  - Authors' Reply.

PMID- 26216007
TI  - Response to Role of a 12-Lead Electrocardiogram in the Diagnosis of Cardiac
      Tamponade as Diagnosed by Transthoracic Echocardiography in Patients With
      Malignant Pericardial Effusion.

PMID- 26216008
TI  - Authors' Reply.

PMID- 26216009
TI  - Hyperamylasemia and pancreatitis following posterior spinal surgery.
AB  - BACKGROUND: Postoperative pancreatitis has primarily been reported as a
      complication of abdominal surgery, but there are some case reports of
      postoperative pancreatitis after spinal surgery. The objective of this study was
      to investigate a case series of hyperamylasemia and pancreatitis following
      posterior spinal surgery. METHODS: The serum amylase level was measured following
      posterior spinal surgery in the prone position. Patients were divided into groups
      with a normal serum amylase level (0-125 IU/L) and with hyperamylasemia (>125
      IU/L), based on the upper limit of normal of 125 IU/L in our institution.
      Relationships among preoperative factors, perioperative factors, and the serum
      amylase level were investigated. RESULTS: Hyperamylasemia (serum amylase >125
      IU/L) following posterior spinal surgery was found in 92 cases (35 %). Among
      perioperative factors, intraoperative estimated blood loss (EBL) and operating
      time were significantly higher in patients with high serum amylase than in
      patients with normal serum amylase (P < 0.01). In a multivariate regression
      model, intraoperative EBL (OR 1.001, 95 % CI 1.000-1.002; P = 0.001) and
      operation time (OR 1.006, 95 % CI 1.003-1.009; P = 0.006) were significantly
      associated with postoperative pancreatitis. Serum amylase levels of >= 5 times
      the upper limit of normal were found in six cases. Five of these cases were
      asymptomatic and one was caused by severe pancreatitis. CONCLUSIONS: In our case
      series, intraoperative blood loss caused a rise in the serum amylase level
      following posterior spinal surgery. Thus, this level should be carefully
      monitored after spinal surgery with significant blood loss. Clinical symptoms of
      pancreatitis, such as abdominal pain and vomiting, should also be monitored
      following spinal surgery.

PMID- 26216010
TI  - Impact of portal vein resection on oncologic long-term outcome in patients with
      hilar cholangiocarcinoma.
AB  - BACKGROUND: Liver resection (LR) for hilar cholangiocarcinoma (HCA) remains
      challenging because of the occurrence of unanticipated vascular and longitudinal
      bile duct invasion. Operative strategies to achieve negative resection margins
      vary, and the benefit of routine portal vein resection (PVR) is discussed
      controversially. METHODS: The data of 60 consecutive patients who underwent LR
      for HCA were analyzed. Twenty-one patients (35.0%) underwent LR plus PVR and 39
      (65.0%) LR only. Clinicopathologic data were evaluated by the use of uni- and
      multivariate analyses. RESULTS: The majority of resections was performed for
      Bismuth-Corlette type III/IV tumors (97.3%). Hepatectomy involved
      trisectionectomies in 41 patients (68.3%). R1 resection margin status was
      identified as adverse prognosis factor for survival (hazard ratio 3.61; P =
      .003). PVR increased the perioperative morbidity (P = .04). The 90-day mortality
      rate was comparable between both groups (P = .70). Negative resection margin
      status was similar between groups (P = .70). The lymph node clearance was equal
      (P = .86). PVR was not associated with a beneficial long-term outcome, the 5-year
      and disease-free survival were comparable (LR only 17.8% vs LR plus PVR 20.0% [P
      = .89] and LR only 10.6% vs LR plus PVR 21.4% [P = .63]). PVR was no prognostic
      factor for tumor-dependent or disease-free survival (hazard ratio 0.64; P = .26
      and hazard ratio 0.76; P = .47). CONCLUSION: The presented data indicate that
      simultaneous PVR has no beneficial impact on oncologic long-term outcome in
      patients undergoing LR for HCA. Because it increases the perioperative morbidity,
      a recommendation for routine application cannot be given.

PMID- 26216011
TI  - Efficacy of Human Chorion Membrane Allograft for Recession Coverage: A Case
      Series.
AB  - BACKGROUND: Membranes of human placentas have been used in the field of medicine
      for skin grafts, treatment of burns, and ulcerated skin conditions with great
      success. The use of placenta allografts in dentistry is a more recent
      development, with the first commercial product being made available in 2008. The
      unique inherent biologic properties in placenta allografts enhance wound healing
      and may propagate regeneration. METHODS: Ten healthy adult patients presenting
      with 21 Miller Class I gingival recession (GR) defects (isolated or adjacent
      multiple) were surgically treated with a modified coronally advanced flap and
      chorion membrane for root coverage. Clinical parameters measured at baseline, 3
      months, and 6 months were probing depth, clinical attachment level, GR height,
      width of keratinized gingiva, and assessment of gingival biotype. Statistical
      analysis was performed to compare the treatment outcomes at the follow-up
      intervals. RESULTS: The results showed statistically significant (P <0.001)
      improvements in all clinical parameters at the 3- and 6-month follow-ups. The
      mean percentage of root coverage at the end of 6 months was 89.92% +/- 15.59%,
      and 14 of 21 treated GR defects showed 100% root coverage. The gingival biotype
      also showed a thick biotype in nine sites that had an initial thin biotype.
      CONCLUSIONS: Fetal membranes possess distinctive properties that can be harnessed
      to promote periodontal healing. The chorion membrane covered by a modified
      coronally advanced flap is a new approach that has shown promising results in
      terms of root coverage, increased width of keratinized tissue, and thickness of
      the gingival biotype.

PMID- 26216012
TI  - Optimization of ZnO-NPs to Investigate Their Safe Application by Assessing Their
      Effect on Soil Nematode Caenorhabditis elegans.
AB  - Zinc oxide nanoparticles (ZnO-NPs) are increasingly receiving attention due to
      their widespread application in cosmetics, pigments and coatings. This has raised
      concerns in the public and scientific communities regarding their unexpected
      health effects. Toxicity effect of ZnO-NPs on the environment was assessed in the
      present study using Caenorhabditis elegans. Multiple toxicity end points
      including their mortality, behaviour, reproduction, in vitro distribution and
      expression of stress response mtl-1 and sod-1 genes were observed to evaluate
      safe application of ZnO-NPs. C. elegans were exposed to 10, 50, and 100 nm ZnO
      NPs (0.1 to 2.0 g/l). Application of 10 nm >=0.7g/l adversely affects the
      survivability of worms and was significantly not affected with exposure of 50 and
      100 nm <=1.0 g/l. However, reproduction was affected at much low concentration as
      compared to their survivability. LC50 was recorded 1.0 +/- 0.06 (g/l) for 100 nm,
      0.90 +/- 0.60 for 50 nm and 0.620 +/- 0.08 for 10 nm. Expression of mtl-1 and sod
      1 was significantly increased with application of 10 nm >=0.7g/l and
      significantly unaffected with exposure of 50 and 100 nm at the same
      concentration. ZnO-NPs (10 nm) had shown even distribution extended nearly the
      entire length of the body. The distribution pattern of ZnO-NPs indicates that the
      intestine is the major target tissues for NP toxicity. Study demonstrates that
      small-sized (10 nm) ZnO-NPs >=0.7g/l is more toxic than larger-sized particles.
      This may be suggested on the basis of available data; application of 50 and 100
      nm <=1.0 g/l ZnO-NPs may be used to the environment as this shows no significant
      toxicity. However, further calibration is warranted to explore safe dose on soil
      compartments prior to their field application. 

PMID- 26216013
TI  - Single-Molecule Break Junctions Based on a Perylene-Diimide Cyano-Functionalized
      (PDI8-CN2) Derivative.
AB  - In this letter, we report the single-molecule conductance properties of a cyano
      functionalized perylene-diimide derivative (PDI8-CN2) investigated with gold nano
      electrodes. This molecule is of large interest for the fabrication of high
      performance and air-stable n-type organic field-effect transistors. Low-bias
      experiments performed on mechanically controllable break junctions reveal the
      presence of two different values of the single-molecule conductance, which differ
      by about two orders of magnitudes. Up to date, this feature was never observed
      for other perylene-diimide compounds having alternative chemical moieties
      attached to the basic aromatic core. Theoretical calculations suggest that the
      highest single-molecule conductance value here observed, comprised between 10(-2)
      and 10(-3) G0, is related to a charge transport path directly linking the two
      cyano groups. 

PMID- 26216014
TI  - Ultrafast Spectroscopy and Red Emission from beta-Ga2O 3/beta-Ga 2S 3 Nanowires.
AB  - Ultrafast pump-probe and transient photoluminescence spectroscopy were used to
      investigate carrier dynamics in beta-Ga2O3 nanowires converted to beta
      Ga2O3/Ga2S3 under H2S between 400 to 600  degrees C. The beta-Ga2O3 nanowires
      exhibited broad blue emission with a lifetime of 2.4 ns which was strongly
      suppressed after processing at 500-600  degrees C giving rise to red emission
      centered at 680 nm with a lifetime of 19 MUs. Differential absorption
      spectroscopy reveals that state filling occurs in states located below the
      conduction band edge before sulfurization, but free carrier absorption is
      dominant in the beta-Ga2O3/Ga2S3 nanowires processed at 500 to 600  degrees C for
      probing wavelengths >500 nm related to secondary excitation of the photo
      generated carriers from the mid-gap states into the conduction band of Ga2S3. 

PMID- 26216015
TI  - Synthesis of CNS active thyrotropin-releasing hormone (TRH)-like peptides:
      Biological evaluation and effect on cognitive impairment induced by cerebral
      ischemia in mice.
AB  - Thyrotropin-releasing hormone (TRH)-like peptides were synthesized by replacing
      critical histidine and pGlu residues in the native peptide. The peptides were
      evaluated in vitro for receptor binding activity assay and in the cell functional
      assay; the peptides exhibit selective basal signaling agonist behavior toward TRH
      R2. For example, peptides 8a, 8b, 8c, 8 f, 8 h, 8 l and 12 d activated TRH-R2
      with potency (EC50) of 0.53 MUM, 0.048 MUM, 0.05 MUM, 0.006 MUM, 0.31 MUM, 0.034
      MUM and 0.004 MUM, respectively. In contrast for signaling activation of TRH-R1,
      the same peptide required higher concentration of 19.35 MUM, 3.98 MUM, 2.54 MUM,
      0.287 MUM, 11.28 MUM, 0.986 MUM and 0.944 MUM, respectively. The results showed
      that peptides were 36.5, 82.9, 50.8, 47.8, 36.3, 32.6 and 235-fold selective to
      TRH-R2 receptor subtype. The peptides were investigated for CNS activity at 10
      MUmol/kg in pentobarbital-induced sleep assay study. Peptides 8c (16.5 +/- 1.4
      min) and 8l (16.5 +/- 2.1 min) displayed excellent CNS activity. In an in vivo
      study, peptide 8c did not cause significant change in the rat plasma TSH levels.
      The peptide 8c was further investigated for neuroprotective potential, and
      significantly reduced infracts volume and neurological score in the focal
      cerebral ischemia model in mice. Peptide 8c also significantly lowered MDA
      levels, indicating reduction of oxidative and enhanced percentage cell survival
      in CA1 region, when compared to ischemic brain.

PMID- 26216016
TI  - Design, synthesis and biological evaluation of saccharin-based N
      hydroxybenzamides as histone deacetylases (HDACs) inhibitors.
AB  - We report the development of a novel series of saccharin-based N
      hydroxybenzamides as histone deacetylases inhibitors. Among them, 6 j exhibited
      potent HDACs inhibitory activity against Hela nuclear extract. Further biological
      evaluation found 6 i showed similar antiproliferative activities in vitro
      compared with the approved SAHA.

PMID- 26216017
TI  - The importance of the 6- and 7-positions of tetrahydroisoquinolines as selective
      antagonists for the orexin 1 receptor.
AB  - Selective antagonism of the orexin 1 (OX1) receptor has been proposed as a
      potential mechanism for treatment of drug addiction. We have previously reported
      studies on the structure-activity relationships of tetrahydroisoquinoline-based
      antagonists. In this report, we elucidated the respective role of the 6- and 7
      substitutions by preparation of a series of either 6-substituted
      tetrahydroisoquinolines (with no 7-substituents) or vice versa. We found that 7
      substituted tetrahydroisoquinolines showed potent antagonism of OX1, indicating
      that the 7-position is important for OX1 antagonism (10 c, Ke = 23.7 nM). While
      the 6-substituted analogs were generally inactive, several 6-amino compounds
      bearing ester groups showed reasonable potency (26 a, Ke = 427 nM). Further, we
      show evidence that suggests several compounds initially displaying insurmountable
      antagonism at the OX1 receptor are competitive antagonists with slow dissociation
      rates.

PMID- 26216019
TI  - Corrigendum.

PMID- 26216018
TI  - Imine/amide-imidazole conjugates derived from 5-amino-4-cyano-N1-substituted
      benzyl imidazole: Microwave-assisted synthesis and anticancer activity via
      selective topoisomerase-II-alpha inhibition.
AB  - Microwave-accelerated synthesis and anticancer activity of novel imine/amide
      imidazole conjugates derived from 5-amino-4-cyano-N1-substituted benzyl imidazole
      against a panel of seven cancer cell lines are reported for the first time.
      Compounds ARK-4, 10 and 12 in the series show promising in vitro anti
      proliferative activity with low micromolar IC50 values against A-459 (lung), Hep
      G2 (liver) and H-460 (liver) cancer cell lines. Compounds caused the increase in
      ROS levels as well as mitochondrial membrane depolarization, which might induce
      apoptosis. Further, mechanistic interventions on biological and molecular
      modeling data supported that compounds inhibited topoisomerase-II selectively. 

PMID- 26216021
TI  - Echinococcus and cancer: unsolved mystery.

PMID- 26216022
TI  - Immune system in cancer and hydatid disease: cross-reactivity vs. immune
      modulation.

PMID- 26216023
TI  - Hymenolepis nana vs. Taenia solium life cycle.

PMID- 26216024
TI  - Beyond our conceived concepts.

PMID- 26216025
TI  - Evaluation of canine-specific minocycline and doxycycline susceptibility
      breakpoints for meticillin-resistant Staphylococcus pseudintermedius isolates
      from dogs.
AB  - BACKGROUND: Using the US Clinical and Laboratory Standards Institute (CLSI) human
      tetracycline breakpoints to predict minocycline and doxycycline susceptibility of
      Staphylococcus pseudintermedius (SP) isolates from dogs is not appropriate
      because they are too high to meet pharmacokinetic/pharmacodynamic data using a
      standard dose. New breakpoints have been approved for doxycycline and proposed
      for minocycline. Revised breakpoints are four dilutions lower than tetracycline
      breakpoints, providing a more conservative standard for classification of
      isolates. HYPOTHESIS/OBJECTIVES: The objectives of this study were to measure
      minimum inhibitory concentrations (MICs) of minocycline and doxycycline of 100
      canine meticillin-resistant SP clinical isolates, compare their susceptibilities
      to minocycline and doxycycline based on current and revised standards, and
      document their tetracycline resistance genes. METHODS: E-test strips were used to
      determine MICs. PCR was used to identify tet genes. RESULTS: Using the human
      tetracycline breakpoint of MIC <= 4 MUg/mL, 76 isolates were susceptible to
      minocycline and 36 isolates were susceptible to doxycycline. In contrast, using
      the proposed minocycline breakpoint (MIC <= 0.25 MUg/mL) and approved doxycycline
      breakpoint (MIC <= 0.125 MUg/mL), 31 isolates were susceptible to both
      minocycline and doxycycline. Thirty-one isolates carried no tet genes, two had
      tet(K) and 67 had tet(M). CONCLUSIONS AND CLINICAL IMPORTANCE: Use of the human
      tetracycline breakpoints misclassified 45 and five of the isolates as susceptible
      to minocycline and doxycycline, respectively. PCR analysis revealed that 43 and
      five of the isolates classified as susceptible to minocycline and doxycycline,
      respectively, possessed the tetracycline resistance gene, tet(M), known to confer
      resistance to both drugs. These results underscore the importance of utilizing
      the proposed minocycline and approved doxycycline canine breakpoints in place of
      human tetracycline breakpoints.

PMID- 26216026
TI  - Novel antiapoptotic effect of TBX15: overexpression of TBX15 reduces apoptosis in
      cancer cells.
AB  - T-box genes regulate development processes, some of these genes having also a
      role in cell proliferation and survival. TBX15 is a T-box transcription factor
      that, recently, has been proposed as a marker in prostate cancer, but its
      function in carcinogenesis is unknown. Here the role of TBX15 in carcinogenesis
      was investigated using thyroid cancer cell lines. First, using western blot
      analysis, we show that the expression of TBX15 was altered in thyroid cancer
      cells lines with respect to normal thyroid cells. Transfection of thyroid cancer
      cells with TBX15, in the presence or absence of camptothecin as a cytotoxic
      agent, proved non effect of TBX15 in cell viability; but, it increased cell
      proliferation after 48 h of transfection (P < 0.01). Consistently, apoptosis was
      reduced in TBX15 transfected cells (P < 0.01) which also showed a decrease of the
      proapoptotic Bax regulator and an increase of the antiapoptotic Bcl2 and Bcl-XL
      regulators. Additionally, siRNA shutdown of constitutive TBX15 increased
      apoptosis. TBX15 transfection did not alter colony formation and cell migration.
      Taken together, these results indicate for the first time an antiapoptotic role
      of TBX15 in cancer cells, suggesting a contribution of TBX15 in carcinogenesis
      and the potential therapeutic target of TBX15. 

PMID- 26216027
TI  - Sodium Butyrate, a Histone Deacetylase Inhibitor, Reverses Behavioral and
      Mitochondrial Alterations in Animal Models of Depression Induced by Early- or
      Late-life Stress.
AB  - The aim of the present study was to evaluate the effects of sodium butyrate on
      depressive-like behavior and mitochondrial alteration parameters in animal models
      of depression induced by maternal deprivation or chronic mild stress in Wistar
      rats. maternal deprivation was established by separating pups from their mothers
      for 3 h daily from postnatal day 1 to day 10. Chronic mild stress was established
      by water deprivation, food deprivation, restraint stress, isolation and flashing
      lights. Sodium butyrate or saline was administered twice a day for 7 days before
      the behavioral tests. Depressive behavior was evaluated using the forced swim
      test. The activity of tricarboxylic acid cycle enzymes (succinate dehydrogenase
      and malate dehydrogenase) and of mitochondrial chain complexes (I, II, II-III and
      IV) was measured in the striatum of rats. From these analyses it can be observed
      that sodium butyrate reversed the depressive-like behavior observed in both
      animal models of depression. Additionally, maternal deprivation and chronic mild
      stress inhibited mitochondrial respiratory chain complexes and increased the
      activity of tricarboxylic acid cycle enzymes. Sodium butyrate treatment reversed 
      maternal deprivation and chronic mild stress- induced dysfunction in the striatum
      of rats. In conclusion, sodium butyrate showed antidepressant effects in maternal
      deprivation and chronic mild stress-treated rats, and this effect can be
      attributed to its action on the neurochemical pathways related to depression.

PMID- 26216028
TI  - Potential targeted therapies for the inflammatory pathogenesis of hepatic
      encephalopathy.
AB  - Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of acute
      and chronic liver dysfunction, and is characterized by a spectrum that ranges
      from mild neuropsychological disturbances to coma. Although ammonia plays a
      critical role in the pathogenesis of HE, the plasma concentrations of ammonia and
      manifest symptoms of HE are not always consistent in patients with HE. Recently,
      a substantial body of evidence has indicated that inflammation acts in concert
      with ammonia in the pathogenesis of HE. Meanwhile, emerging novel and potential
      therapeutic strategies, including N-acetylcysteine, hypothermia, minocycline, non
      steroidal anti-inflammatory drugs, tumour necrosis factor-alpha antagonists and
      p38 inhibitors, have been reported to ameliorate systemic inflammation and
      neuroinflammation, improve or reverse neuropsychiatric manifestations, and
      prevent the onset and progression of HE in patients and/or animal models of acute
      or chronic liver failure. These results point to the possible therapeutic utility
      of decreasing inflammation in the treatment of HE, and translation of these
      experimental results to the clinic may provide novel and promising therapeutic
      approaches for patients with HE secondary to acute or chronic liver failure. This
      review will provide an overview of these potential targeted therapies in the
      prophylaxis and treatment of HE. 

PMID- 26216029
TI  - Efficacy and safety of simeprevir for chronic hepatitis virus C genotype 1
      infection: A meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: To gain a profile of the efficacy and safety of
      simeprevir-based triple therapy in chronic hepatitis virus C (HCV) genotype 1
      infected patients. METHODS: We searched in Medline, Embase, Cochrane database of
      systematic reviews and CINAHL for randomized controlled trials (RCTs) without
      year or language restriction. Eligible studies should evaluate simeprevir plus
      peginterferon and ribavirin combination therapy for chronic hepatitis C genotype
      1 patients, while the standard peginterferon and ribavirin therapy as control
      group. Results must include the data of achieving sustained virological response
      (SVR), rapid virological response (RVR), incidence of discontinuation and severe
      adverse events (SAE). RESULTS: Six RCTs (2209 patients) were included. The
      proportion of achieving SVR at 12 weeks after planned end of treatment (SVR12)
      was significantly higher in the simeprevir group than in the control group
      (RR=1.69, 95%CI: 1.37-2.08, P<0.001). The results also showed that the RVR rate
      was significantly higher in the simeprevir group (RR=9.57, 95%CI: 5.82-15.73,
      P<0.001). The addition of simeprevir was not accompanied with the increased risks
      of SAE (RR=0.67, 95%CI: 0.47-0.94, P=0.023). The incidence of discontinuation due
      to adverse events seems a little higher in simeprevir group than in the control
      group (3.0% vs. 1.1%), though there was no statistical difference (RR=1.26,
      95%CI: 0.58-2.74, P=0.566). CONCLUSION: Simeprevir-based triple therapy
      significantly increase the SVR12 rate and RVR rate without increasing the
      incidences of SAE and treatment discontinuation due to adverse events. However,
      further inquiries on the long-term safety of simeprevir are required in future.

PMID- 26216030
TI  - Inflammasome activation in the liver: Focus on alcoholic and non-alcoholic
      steatohepatitis.
AB  - Upregulation of the inflammatory cascade is a major element both in the
      progression of steatohepatitis to severe alcoholic hepatitis as well as in the
      progression of NASH to advanced NASH with fibrosis. The mechanisms underpinning
      these changes are only partially understood. Activation of the inflammatory
      cascade requires multiple stimuli and in this report, we discuss the role of
      inflammasomes that activate IL-1beta as well as the sterile and pathogen-derived
      danger signals that results in inflammasome activation and inflammation in
      alcoholic and non-alcoholic steatohepatitis. The dynamics of inflammasome
      activation, the cell types involved and the trigger signals appear to be somewhat
      different between ASH and NASH. Further studies are needed to dissect the
      pathology-related differences between these two major forms of steatohepatitis.
      Clinical and therapeutic implications of inflammasome activation in
      steatohepatitis are also discussed. 

PMID- 26216032
TI  - Mieap suppresses murine intestinal tumor via its mitochondrial quality control.
AB  - Mieap, a novel p53-inducible protein, plays a key role in maintaining healthy
      mitochondria in various pathophysiological states. Here, we show that Mieap
      deficiency in Apc(Min/+) mice is strikingly associated with the malignant
      progression of murine intestinal tumors. To understand the role that Mieap plays
      in in vivo tumorigenesis, we generated Mieap heterozygous (Apc(Min/+) Mieap(+/-))
      and homozygous (Apc(Min/+) Mieap(-/-)) Apc(Min/+) mice. Interestingly, the
      Apc(Min/+) mice with the Mieap(+/-) and Mieap(-/-) genetic background revealed
      remarkable shortening of the lifetime compared to Apc(Min/+) mice because of
      severe anemia. A substantial increase in the number and size of intestinal polyps
      was associated with Mieap gene deficiency. Histopathologically, intestinal tumors
      in the Mieap-deficient Apc(Min/+) mice clearly demonstrated advanced grades of
      adenomas and adenocarcinomas. We demonstrated that the significant increase in
      morphologically unhealthy mitochondria and trace accumulations of reactive oxygen
      species may be mechanisms underlying the increased malignant progression of the
      intestinal tumors of Mieap-deficient Apc(Min/+) mice. These findings suggest that
      the Mieap-regulated mitochondrial quality control plays a critical role in
      preventing mouse intestinal tumorigenesis. 

PMID- 26216033
TI  - Long-term outcome with cardiac resynchronization therapy in mild heart failure
      patients with left bundle branch block from US and Europe MADIT-CRT.
AB  - Early intervention with cardiac resynchronization therapy with defibrillator (CRT
      D) in mild heart failure (HF) patients with a left bundle branch block (LBBB) ECG
      pattern was associated with a significant reduction in mortality in the long-term
      MADIT-CRT trial. Whether patients in MADIT-CRT enrolled from centers in the USA
      and in Europe have different long-term clinical response to CRT-D remains
      unknown. We compared the baseline clinical characteristics and clinical and
      echocardiographic long-term clinical response to CRT-D between MADIT-CRT patients
      with LBBB who were enrolled in USA (n = 871) and European centers (n = 392).
      Although European patients had more advanced heart disease than US patients, CRT
      D was associated with similar 60 % (p < 0.001) reductions in the risk of HF in US
      and European patients when compared to ICD-only therapy after adjustment for
      relevant baseline clinical covariates. US patients had significant long-term
      mortality reduction (38 %, p = 0.02) while among European patients the survival
      benefit associated with CRT-D was not statistically significant (HR 0.73, p =
      0.18); subgroup analyses revealed a significantly greater CRT-D benefit among
      women who were enrolled in the USA, whereas no significant gender difference in
      the clinical benefit of CRT-D was observed in the European cohort. Reverse
      remodeling at 1 year was associated with significantly better clinical outcomes
      in both groups. Despite differences in baseline disease severity, European and US
      patients with LBBB experienced a similar clinical and echocardiographic response
      to cardiac resynchronization therapy during long-term follow-up. CLINICAL TRIAL
      REGISTRATION: http://clinicaltrials.gov/ct2/show/NCT00180271 .

PMID- 26216034
TI  - Re: Diagnostic accuracy of placental growth factor and ultrasound parameters to
      predict the small-for-gestational-age infant in women presenting with reduced
      symphysis-fundus height. M. Griffin, P. T. Seed, L. Webster, J. Myers, L.
      Mackillop, N. Simpson, D. Anumba, A. Khalil, M. Denbow, A. Sau, K. Hinshaw, P.
      von Dadelszen, S. Benton, J. Girling, C. W. G. Redman, L. C. Chappell and A. H.
      Shennan. Ultrasound Obstet Gynecol 2015; 46: 182-190.

PMID- 26216035
TI  - Re: Impact on obstetric outcome of third-trimester screening for small-for
      gestational-age fetuses. R. Callec, C. Lamy, E. Perdriolle-Galet, C. Patte, B.
      Heude and O. Morel. Ultrasound Obstet Gynecol 2015; 46: 216-220.

PMID- 26216036
TI  - Reply.

PMID- 26216037
TI  - Calculation of fetal cerebroplacental ratio multiples of the median: are all
      methods equivalent?

PMID- 26216038
TI  - Re: First-trimester screening for pre-eclampsia: moving from personalized risk
      prediction to prevention.

PMID- 26216040
TI  - Paying the costs of reproduction.
AB  - When a female fly mates it produces a hormone that increases the size of its
      midgut and enhances fat metabolism in order to provide the energy needed for
      reproduction. 

PMID- 26216039
TI  - Endocrine remodelling of the adult intestine sustains reproduction in Drosophila.
AB  - The production of offspring is energetically costly and relies on incompletely
      understood mechanisms that generate a positive energy balance. In mothers of many
      species, changes in key energy-associated internal organs are common yet poorly
      characterised functionally and mechanistically. In this study, we show that, in
      adult Drosophila females, the midgut is dramatically remodelled to enhance
      reproductive output. In contrast to extant models, organ remodelling does not
      occur in response to increased nutrient intake and/or offspring demands, but
      rather precedes them. With spatially and temporally directed manipulations, we
      identify juvenile hormone (JH) as an anticipatory endocrine signal released after
      mating. Acting through intestinal bHLH-PAS domain proteins Methoprene-tolerant
      (Met) and Germ cell-expressed (Gce), JH signals directly to intestinal
      progenitors to yield a larger organ, and adjusts gene expression and sterol
      regulatory element-binding protein (SREBP) activity in enterocytes to support
      increased lipid metabolism. Our findings identify a metabolically significant
      paradigm of adult somatic organ remodelling linking hormonal signals, epithelial
      plasticity, and reproductive output. 

PMID- 26216041
TI  - Sleep deprivation suppresses aggression in Drosophila.
AB  - Sleep disturbances negatively impact numerous functions and have been linked to
      aggression and violence. However, a clear effect of sleep deprivation on
      aggressive behaviors remains unclear. We find that acute sleep deprivation
      profoundly suppresses aggressive behaviors in the fruit fly, while other social
      behaviors are unaffected. This suppression is recovered following post
      deprivation sleep rebound, and occurs regardless of the approach to achieve sleep
      loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits
      changes in aggression upon sleep deprivation, and reduced aggression places sleep
      deprived flies at a competitive disadvantage for obtaining a reproductive
      partner. These findings demonstrate an interaction between two phylogenetically
      conserved behaviors, and suggest that previous sleep experiences strongly
      modulate aggression with consequences for reproductive fitness. 

PMID- 26216042
TI  - Mycobacterium ulcerans dynamics in aquatic ecosystems are driven by a complex
      interplay of abiotic and biotic factors.
AB  - Host-parasite interactions are often embedded within complex host communities and
      can be influenced by a variety of environmental factors, such as seasonal
      variations in climate or abiotic conditions in water and soil, which confounds
      our understanding of the main drivers of many multi-host pathogens. Here, we take
      advantage of a combination of large environmental data sets on Mycobacterium
      ulcerans (MU), an environmentally persistent microorganism associated to
      freshwater ecosystems and present in a large variety of aquatic hosts, to
      characterize abiotic and biotic factors driving the dynamics of this pathogen in
      two regions of Cameroon. We find that MU dynamics are largely driven by seasonal
      climatic factors and certain physico-chemical conditions in stagnant and slow
      flowing ecosystems, with an important role of pH as limiting factor. Furthermore,
      water conditions can modify the effect of abundance and diversity of aquatic
      organisms on MU dynamics, which suggests a different contribution of two MU
      transmission routes for aquatic hosts (trophic vs environmental transmission)
      depending on local abiotic factors. 

PMID- 26216044
TI  - Evolving concepts in tumour lysis syndrome management - response to Ayed et al.

PMID- 26216043
TI  - Monoglyceride lipase: Structure and inhibitors.
AB  - Monoglyceride lipase (MGL), the main enzyme responsible for the hydrolytic
      deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), is an
      intracellular serine hydrolase that plays critical roles in many physiological
      and pathological processes, such as pain, inflammation, neuroprotection and
      cancer. The crystal structures of MGL that are currently available provide
      valuable information about how this enzyme might function and interact with site
      directed small-molecule inhibitors. On the other hand, its conformational
      equilibria and the contribution of regulatory cysteine residues present within
      the substrate-binding pocket or on protein surface remain open issues. Several
      classes of MGL inhibitors have been developed, from early reversible ones, such
      as URB602 and pristimerin, to carbamoylating agents that react with the catalytic
      serine, such as JZL184 and more recent O-hexafluoroisopropyl carbamates. Other
      inhibitors that modulate MGL activity by interacting with conserved regulatory
      cysteines act through mechanisms that deserve to be more thoroughly investigated.

PMID- 26216045
TI  - Murine pattern recognition receptor dectin-1 is essential in the development of
      experimental autoimmune uveoretinitis.
AB  - Mycobacteria in complete Freund's adjuvant (CFA) are an essential component of
      immunization protocols in a number of autoimmune disease animal models including
      experimental autoimmune encephalomyelitis and uveoretinitis (EAE and EAU,
      respectively). We determined the role in EAU of two C-type lectin receptors on
      myeloid cells that recognize and respond to mycobacteria. Using receptor-specific
      antibodies and knockout mice, we demonstrated for the first time that the
      macrophage mannose receptor delays disease development but does not affect
      severity. In contrast, dectin-1 is critically involved in the development of CFA
      mediated EAU. Disease severity is reduced in dectin-1 knockout mice and antibody
      blockade of dectin-1 during the induction, but not the effector phase, prevents
      EAU development. Significantly, similar blockade of dectin-1 in vivo has no
      effect in non-CFA-mediated, spontaneously induced or adoptive transfer models of
      EAU. Thus dectin-1 plays a critical role in the ability of complete Freund's
      adjuvant to induce EAU in mice. 

PMID- 26216046
TI  - A Cost Analysis of the American Board of Internal Medicine's Maintenance-of
      Certification Program.
AB  - BACKGROUND: In 2014, the American Board of Internal Medicine (ABIM) substantially
      increased the requirements and fees for its maintenance-of-certification (MOC)
      program. Faced with mounting criticism, the ABIM suspended certain content
      requirements in February 2015 but retained the increased fees and number of
      modules. An objective appraisal of the cost of MOC would help inform upcoming
      consultations about MOC reform. OBJECTIVE: To estimate the total cost of the 2015
      version of the MOC program ("2015 MOC") and the incremental cost relative to the
      2013 version ("2013 MOC"). DESIGN: Decision analytic model. DATA SOURCES:
      Published literature. TARGET POPULATION: All ABIM-certified U.S. physicians. TIME
      HORIZON: 10 years (2015 to 2024). PERSPECTIVE: Societal. INTERVENTION: 2015 MOC.
      OUTCOME MEASURES: Testing costs (ABIM fees) and time costs (monetary value of
      physician time). RESULTS OF BASE-CASE ANALYSIS: Internists will incur an average
      of $23 607 (95% CI, $5380 to $66 383) in MOC costs over 10 years, ranging from
      $16 725 for general internists to $40 495 for hematologists-oncologists. Time
      costs account for 90% of MOC costs. Cumulatively, 2015 MOC will cost $5.7 billion
      over 10 years, $1.2 billion more than 2013 MOC. This includes $5.1 billion in
      time costs (resulting from 32.7 million physician-hours spent on MOC) and $561
      million in testing costs. RESULTS OF SENSITIVITY ANALYSIS: Costs are sensitive to
      time spent on MOC and MOC credits obtainable from current continuing education
      activities. LIMITATION: Precise estimates of time required for MOC are not
      available. CONCLUSION: The ABIM MOC program will generate considerable costs,
      predominantly due to demands on physician time. A rigorous evaluation of its
      effect on clinical and economic outcomes is warranted to balance potential gains
      in health care quality and efficiency against the high costs identified in this
      study. PRIMARY FUNDING SOURCE: University of California, San Francisco, and the
      U.S. Department of Veterans Affairs.

PMID- 26216031
TI  - Short-term weight gain after antiretroviral therapy initiation and subsequent
      risk of cardiovascular disease and diabetes: the D:A:D study.
AB  - OBJECTIVES: The aim of the study was to assess the impact of the gain in body
      mass index (BMI) observed immediately after antiretroviral therapy (ART)
      initiation on the subsequent risk of cardiovascular disease (CVD) and diabetes.
      METHODS: We analysed data from the Data Collection on Adverse Events of Anti-HIV
      Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of
      myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main
      exposure variable was change in BMI from ART initiation (pre-ART) to 1 year after
      initiation (continuous variable) in treatment-naive individuals initiating ART
      with no history of CVD or diabetes (for respective outcomes). BMI [weight
      (kg)/(height (m))(2)] was categorized as underweight (< 18.5), normal (18.5-25),
      overweight (25-30) and obese (> 30). Poisson regression models were fitted
      stratified for each pre-ART BMI category to allow for category-specific estimates
      of incidence rate ratio (IRR). Models were adjusted for pre-ART BMI and CD4
      count, key known risk factors (time-updated where possible) and calendar year.
      RESULTS: A total of 97 CVD events occurred in 43,982 person-years (n = 9321) and
      125 diabetes events in 43,278 person-years (n = 9193). In fully adjusted analyses
      for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of
      ART, by pre-ART BMI category, was: underweight, 0.90 (0.60-1.37); normal, 1.18
      (1.05-1.33); overweight, 0.87 (0.70-1.10), and obese, 0.95 (0.71-1.28) (P for
      interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95%
      confidence interval 1.03 to 1.21), regardless of pre-ART BMI (P for interaction >
      0.05). CONCLUSIONS: Short-term gain in BMI following ART initiation appeared to
      increase the longer term risk of CVD, but only in those with pre-ART BMI in the
      normal range. It was also associated with increased risk of diabetes regardless
      of pre-ART BMI.

PMID- 26216048
TI  - Comparison of micafungin and voriconazole as empirical antifungal therapies in
      febrile neutropenic patients with hematological disorders: a randomized
      controlled trial.
AB  - OBJECTIVES: In cases of hematological malignancy, patients with persistent fever
      and neutropenia receive antifungal empirical therapy to prevent and treat
      invasive fungal infections. The clinical efficacy and safety of micafungin and
      voriconazole were compared. METHODS: In this randomized, cooperative group, open
      label trial, we assessed and compared the efficacy and safety of micafungin and
      voriconazole as an empirical antifungal therapy in febrile neutropenic patients
      with hematological malignancy. Patients were classified according to invasive
      fungal infection risk. RESULTS: There were no significant differences in clinical
      efficacy between the two treatments, evaluated based on (i) successful treatment
      of baseline fungal infection (no evaluation), (ii) absence of breakthrough fungal
      infection (P = 0.106), (iii) survival for >=7 days after study completion (P =
      0.335), (iv) premature study discontinuation due to poor efficacy (P = 0.424),
      and (v) resolution of fever during neutropenia (P = 0.756). Discontinuation due
      to drug-related adverse events (grades 3-4) occurred less frequently in the
      micafungin group (P = 0.005). CONCLUSIONS: The clinical efficacy did not differ
      between micafungin and voriconazole. Micafungin was generally better tolerated
      than voriconazole when given as an empirical antifungal therapy in patients with
      persistent fever and neutropenia.

PMID- 26216049
TI  - A COX/5-LOX Inhibitor Licofelone Revealed Anticonvulsant Properties Through iNOS
      Diminution in Mice.
AB  - Licofelone is a COX/5-LOX inhibitor, which recently was approved as an effective
      treatment for osteoarthritis. Beside its analgesic and anti-inflammatory effects,
      some reports show neuro-protective properties for this agent in central nervous
      system. Several lines of evidence declare the involvement of COX or LOX
      isoenzymes in epileptic disorders. To set the foundation for future research into
      the neurobiology of licofelone as a potential therapeutic agent, we studied the
      effect of licofelone in an animal model of epilepsy. Although different
      neurotransmitters and neuro-modulators like nitric oxide were introduced as
      suggested targets of licofelone, the underlying mechanisms of central effects of
      this drug are not still fully understood. We have utilized pentylenetetrazole
      induced clonic seizure model to investigate the behavioral consequences of
      licofelone administration and its possible mechanisms in seizure susceptibility.
      Licofelone revealed anticonvulsant properties at the dose of 10 mg/kg (i.p) or
      higher in mice. Pre-treatment with NO (nitric oxide) donor, L-arginine, reversed
      this anticonvulsant effects dose dependently. L-NAME, as a non-selective nitric
      oxide synthase (NOS) inhibitor, potentiated the anticonvulsant effects of
      licofelone. A neuronal NOS inhibitor, 7-NI did not affect seizure threshold alone
      or in combination with licofelone. Using non-effective doses of selective
      inhibitors of inducible NOS, aminoguanidine or 1400W, significantly increased the
      seizure threshold when were accompanied by licofelone in low doses. These data
      support the involvement of NO as an important role player in the central neuro
      protective properties of licofelone. Furthermore, it implies that down regulation
      of iNOS seems crucial for anticonvulsant properties of this COX/5-LOX inhibitor
      in seizure susceptibility. 

PMID- 26216050
TI  - Effect of Imipramine, Paroxetine, and Lithium Carbonate on Neurobehavioral
      Changes of Streptozotocin in Rats: Impact on Glycogen Synthase Kinase-3 and Blood
      Glucose Level.
AB  - Recent studies have demonstrated a scrutinized association of diabetes mellitus
      with depressive symptoms and major depression. Glycogen synthase kinase-3 (GSK-3)
      is a protein kinase enzyme constitutively active in non-stimulated cells and in
      multiple signalings. Independent lines of research provide a converging evidence
      for an involvement of GSK-3 in the regulation of behavior and hyperglycemia. The
      present study revealed that streptozotocin (STZ)-induced diabetic rats were found
      to show lengthened duration of immobility in the forced-swimming test (FST) and
      reduced locomotor and exploratory activities in the open-field test (OFT).
      Imipramine (15 mg/kg), Paroxetine (10 mg/kg) and lithium carbonate (36.94 mg/kg)
      for 14 days reduced immobility behavior in FST. Paroxetine and lithium carbonate
      increased the locomotor and exploratory activities, while imipramine decreased
      the locomotor activity in the OFT. Imipramine and lithium carbonate reduced the
      blood glucose level while paroxetine didn't alter it. STZ-induced diabetes
      increased GSK-3 gene expression which was determined using the reverse
      transcription-quantitative polymerase chain reaction test, while the three drugs
      decreased its expression. It can be concluded that lithium carbonate and
      imipramine can control both hyperglycemia and the associated symptoms of
      depression at the same time by inhibiting GSK-3 activity. On the other hand,
      paroxetine may only manage the depressive-like symptoms associated with diabetes
      through modulating the enzyme GSK-3, without changing blood glucose levels. 

PMID- 26216052
TI  - Quantitative myocardial perfusion PET parametric imaging at the voxel-level.
AB  - Quantitative myocardial perfusion (MP) PET has the potential to enhance detection
      of early stages of atherosclerosis or microvascular dysfunction, characterization
      of flow-limiting effects of coronary artery disease (CAD), and identification of
      balanced reduction of flow due to multivessel stenosis. We aim to enable
      quantitative MP-PET at the individual voxel level, which has the potential to
      allow enhanced visualization and quantification of myocardial blood flow (MBF)
      and flow reserve (MFR) as computed from uptake parametric images. This framework
      is especially challenging for the (82)Rb radiotracer. The short half-life enables
      fast serial imaging and high patient throughput; yet, the acquired dynamic PET
      images suffer from high noise-levels introducing large variability in uptake
      parametric images and, therefore, in the estimates of MBF and MFR. Robust
      estimation requires substantial post-smoothing of noisy data, degrading valuable
      functional information of physiological and pathological importance. We present a
      feasible and robust approach to generate parametric images at the voxel-level
      that substantially reduces noise without significant loss of spatial resolution.
      The proposed methodology, denoted physiological clustering, makes use of the
      functional similarity of voxels to penalize deviation of voxel kinetics from
      physiological partners. The results were validated using extensive simulations
      (with transmural and non-transmural perfusion defects) and clinical studies.
      Compared to post-smoothing, physiological clustering depicted enhanced
      quantitative noise versus bias performance as well as superior recovery of
      perfusion defects (as quantified by CNR) with minimal increase in bias. Overall,
      parametric images obtained from the proposed methodology were robust in the
      presence of high-noise levels as manifested in the voxel time-activity-curves. 

PMID- 26216051
TI  - Effect of Bradykinin Postconditioning on Ischemic and Toxic Brain Damage.
AB  - Brain damage caused by ischemia or toxic agents leads in selectively vulnerable
      regions to apoptosis-like delayed neuronal death and can result in irreversible
      damage. Selectively vulnerable neurons of the CA1 area of hippocampus are
      particularly sensitive to ischemic damage. We investigated the effects of
      bradykinin (BR) postconditioning on cerebral ischemic and toxic injury. Transient
      forebrain ischemia was induced by four-vessel occlusion for 10 min and toxic
      injury was induced by trimethyltin (TMT, 8 ug/kg i.p.). BR as a postconditioner
      at a dose of 150 ug/kg was applied intraperitoneally 48 h after ischemia or TMT
      intoxication. Experimental animals were divided into groups according to the
      length of survival (short-3 and 7 days, and long-28 days survival) and according
      to the applied ischemic or toxic injury. Glutamate concentration was lowered in
      both CA1 and dentate gyrus areas of hippocampus after the application of BR
      postconditioning in both ischemic and toxic brain damage. The number of
      degenerated neurons in the hippocampal CA1 region was significantly lower in BR
      treated ischemic and toxic groups compared to vehicle group. The behavioral test
      used in our experiments confirms also the memory improvement in conditioned
      animals. The rats' ability to form spatial maps and learn was preserved, which is
      visible from our Barnes maze results. By using the methods of delayed
      postconditioning is possible to stimulate the endogenous protective mechanisms of
      the organism and induce the neuroprotective effect. In this study we demonstrated
      that BR postconditioning, if applied before the onset of irreversible
      neurodegenerative changes, induced neuroprotection against ischemic or toxic
      injury.

PMID- 26216053
TI  - Learning to ensure patient safety in clinical settings: comparing Finnish and
      British nursing students' perceptions.
AB  - AIMS AND OBJECTIVES: To explore and compare Finnish and British nursing students'
      perceptions of their learning about patient safety in clinical settings.
      BACKGROUND: Patient safety culture and practices in different health care
      organisations and clinical units varies, posing challenges for nursing students'
      learning about patient safety during their clinical placements. Patient safety as
      a growing international concern has challenged health care professionals globally
      requiring a comprehensive review. International studies comparing nursing
      education about patient safety are lacking. DESIGN: A cross-sectional comparative
      study. METHOD: The participants were final year preregistration nursing students
      from two universities of applied sciences in Finland (n = 195) and from two
      universities in England, UK (n = 158). The data were collected with the Patient
      Safety in Nursing Education Questionnaire and analysed with principal component
      analysis, Pearson Chi-Square and Mann-Whitney U tests and logistic regression.
      RESULTS: Finnish nursing students had significantly more critical perceptions on
      their learning about patient safety in clinical settings than their British
      peers. A strong predictor for differences was supportive and systems-based
      approaches in learning to ensure patient safety. Notably, fewer Finnish students
      had practiced reporting of incidents in clinical settings compared to British
      students. In both countries, the students held learning about patient safety in
      higher esteem compared to their learning experiences in clinical settings.
      CONCLUSIONS: Nursing students appear to want more learning opportunities related
      to patient safety compared to the reality in clinical settings. Learning
      systematically from errors in a supportive environment and having systems-based
      approaches to ensure patient safety are essential elements for nursing students'
      learning about safe practice. Finnish students seem to experience more barriers
      in learning about safe practices and to report errors than the British students.
      RELEVANCE TO CLINICAL PRACTICE: Health care organisations and professionals with
      responsibilities for patient safety should seek to standardise the preparation of
      nursing students incorporating requisite international standards and benchmarks.

PMID- 26216054
TI  - Tissue engineered vascular grafts: Origins, development, and current strategies
      for clinical application.
AB  - Since the development of a dependable and durable synthetic non-autogenous
      vascular conduit in the mid-twentieth century, the field of vascular surgery has
      experienced tremendous growth. Concomitant with this growth, development in the
      field of bioengineering and the development of different tissue engineering
      techniques have expanded the armamentarium of the surgeon for treating a variety
      of complex cardiovascular diseases. The recent development of completely tissue
      engineered vascular conduits that can be implanted for clinical application is a
      particularly exciting development in this field. With the rapid advances in the
      field of tissue engineering, the great hope of the surgeon remains that this
      conduit will function like a true blood vessel with an intact endothelial layer,
      with the ability to respond to endogenous vasoactive compounds. Eventually, these
      engineered tissues may have the potential to supplant older organic but not truly
      biologic technologies, which are used currently. 

PMID- 26216055
TI  - Selective elimination of isolectin B4-binding trigeminal neurons enhanced
      formalin-induced nocifensive behavior in the upper lip of rats and c-Fos
      expression in the trigeminal subnucleus caudalis.
AB  - The functional significance of non-peptidergic C-fibers in orofacial pain
      processing is largely unknown. The present study examined the effects of the
      selective elimination of isolectin B4 (IB4)-binding (IB4(+)) neurons on formalin
      induced face rubbing behavior (FRB) in the upper lip of rats and c-Fos
      immunoreactive (c-Fos-IR) cells in the trigeminal subnucleus caudalis (Vc). IB4
      conjugated to neurotoxin, saporin (IB4-Sap), blank-saporin (Bl-Sap), or saline
      (Sal) was injected into the cisterna magna. IB4-Sap treatments significantly
      decreased IB4(+) terminals in lamina II of Vc and IB4(+) trigeminal ganglia
      neurons, whereas Sal- and BI-Sap treatments did not. The number of formalin
      induced FRB 15-30 min after the formalin injection was significantly higher in
      IB4-Sap-treated rats than in Sal- or Bl-Sap-treated rats, and was associated with
      an increase in c-Fos-IR cells. The systemic preadministration of the GABAA
      antagonist, bicuculline, and agonist, muscimol, had stronger decreasing effects
      on FRB and c-Fos-IR cells in IB4-Sap-treated rats than the preadministration of
      Sal, whereas the opposite effects were observed in Sal- and Bl-Sap-treated rats.
      These results indicate that IB4(+) neurons in the trigeminal nerve play
      antinociceptive regulatory roles in formalin-induced orofacial pain processing
      and that GABAA receptor functions at segmental and supratrigeminal sites have
      complex modulatory influences on antinociceptive roles.

PMID- 26216057
TI  - DNA damage control: regulation and functions of checkpoint kinase 1.
AB  - Checkpoint kinase 1 (Chk1) is a master regulator of the DNA damage and
      replication checkpoints in vertebrate cells. When activated via phosphorylation
      by its upstream regulatory kinase, ATR, Chk1 prevents cells with damaged or
      incompletely replicated DNA from entering mitosis, and acts to stabilize stalled
      replication forks and suppress replication origin firing when DNA synthesis is
      inhibited. Chk1 blocks mitosis by maintaining high levels of inhibitory tyrosine
      phosphorylation of the mitotic cyclin-dependent kinase 1; however, the mechanisms
      that underlie replication fork stabilization and suppression of origin firing are
      less well defined. Although Chk1 function is evidently acutely regulated during
      these responses, how this occurs at the molecular level is incompletely
      understood. Recent evidence that Chk1 contains a 'kinase-associated 1' domain
      within its regulatory C-terminal region promises new insights. Additional
      modifications catalysed by other protein kinases, such as cyclin-dependent kinase
      1, Akt, and RSK, can combine with ubiquitylation to regulate Chk1 subcellular
      localization and protein stability. Interestingly, it is clear that Chk1 has less
      well-defined functions in homologous recombination, chromatin modification, gene
      expression, spindle checkpoint proficiency, and cytokinesis. Here, we provide an
      overview of Chk1 regulation and functions, with an emphasis on unresolved
      questions that merit further research. 

PMID- 26216058
TI  - Intradural prepontine chordoma in an 11-year-old boy. A case report.
AB  - CASE REPORT: The authors report a case of an 11-year-old boy that presented with
      headache and vomiting that was present for several months. CT and MR imaging
      revealed a large prepontine mass and an obstructive hydrocephalus. A
      ventriculoperitoneal shunt was inserted, and in a second operation, a
      radiologically proven total resection was performed, using a left frontotemporal
      transsylvian approach. The tumour showed no involvement of the dura or clivus.
      Histological examination showed the characteristics of a chordoma. No further
      adjuvant treatment was given. The patient remained disease or tumour free after a
      6-year follow-up. DISCUSSION: Intradural chordomas are extremely rare tumours
      that originate from notochordal remnants. Only three other cases have been
      reported in the paediatric population. Ecchordosis physaliphora (EP) is an
      ectopic notochordal remnant that has a similar biological behaviour and is
      difficult to distinguish from intradural chordomas. They might exist in a
      continuum from benign notochordal tumour to malignant chordoma. A surgical
      resection without adjuvant radiation therapy is suggested to be the treatment of
      choice in the paediatric population. CONCLUSION: The authors describe a rare case
      of an intradural prepontine chordoma in an 11-year-old boy that stayed disease
      free after a 6-year follow-up.

PMID- 26216056
TI  - Mutations in human IFT140 cause non-syndromic retinal degeneration.
AB  - Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are two
      genetically heterogeneous retinal degenerative disorders. Despite the
      identification of a number of genes involved in LCA and RP, the genetic etiology
      remains unknown in many patients. In this study, we aimed to identify novel
      disease-causing genes of LCA and RP. Retinal capture sequencing was initially
      performed to screen mutations in known disease-causing genes in different cohorts
      of LCA and RP patients. For patients with negative results, we performed whole
      exome sequencing and applied a series of variant filtering strategies. Sanger
      sequencing was done to validate candidate causative IFT140 variants. Exome
      sequencing data analysis led to the identification of IFT140 variants in multiple
      unrelated non-syndromic LCA and RP cases. All the variants are extremely rare and
      predicted to be damaging. All the variants passed Sanger validation and
      segregation tests provided that the family members' DNA was available. The
      results expand the phenotype spectrum of IFT140 mutations to non-syndromic
      retinal degeneration, thus extending our understanding of intraflagellar
      transport and primary cilia biology in the retina. This work also improves the
      molecular diagnosis of retinal degenerative disease.

PMID- 26216059
TI  - The role of early intra-operative MRI in partial resection of optic
      pathway/hypothalamic gliomas in children.
AB  - INTRODUCTION: Optic pathway/hypothalamic gliomas (OPHGs) are generally benign but
      situated in an exquisitely sensitive brain region. They follow an unpredictable
      course and are usually impossible to resect completely. We present a case series
      of 10 patients who underwent surgery for OPHGs with the aid of intra-operative
      MRI (ioMRI). The impact of ioMRI on OPHG resection is presented, and a role for
      ioMRI in partial resection is discussed. METHODS: Ten patients with OPHGs managed
      surgically utilising ioMRI at Alder Hey Children's Hospital between 2010 and 2013
      were retrospectively identified. Demographic and relevant clinical data were
      obtained. MRI was used to estimate tumour volume pre-operatively and post
      resection. If ioMRI demonstrated that further resection was possible, second-look
      surgery, at the discretion of the operating surgeon, was performed, followed by
      post-operative imaging to establish the final status of resection. Tumour volume
      was estimated for each MR image using the MRIcron software package. RESULTS:
      Control of tumour progression was achieved in all patients. Seven patients had,
      on table, second-look surgery with significant further tumour resection following
      ioMRI without any surgically related mortality or morbidity. The median
      additional quantity of tumour removed following second-look surgery, as a
      percentage of the initial total volume, was 27.79% (range 11.2-59.2%). The final
      tumour volume remaining with second-look surgery was 23.96 vs. 33.21% without (p
      = 0.1). CONCLUSIONS: OPHGs are technically difficult to resect due to their
      eloquent location, making them suitable for debulking resection only. IoMRI
      allows surgical goals to be reassessed intra-operatively following primary
      resection. Second-look surgery can be performed if possible and necessary and
      allows significant quantities of extra tumour to be resected safely. Although the
      clinical significance of additional tumour resection is not yet clear, we suggest
      that ioMRI is a safe and useful additional tool, to be combined with advanced
      neuronavigation techniques for partial tumour resection.

PMID- 26216061
TI  - Service user involvement in giving mental health students feedback on placement:
      A participatory action research study.
AB  - BACKGROUND: Although the drive to engage service users in service delivery,
      research and education has mainstream acceptance, it is not easy to achieve
      meaningful involvement. The contribution that could potentially be made by users
      whilst accessing services is often overlooked. OBJECTIVES AND PARTICIPANTS: This
      study involved stakeholders (mentors, service users and a lecturer) working
      together to design, evaluate and refine a system enabling students to seek
      feedback from service users. The feedback concerned mental health students'
      interpersonal skills and occurred whilst on practice placement. This research
      aimed to explore the experiences of those concerned when nine students attempted
      to learn from rather than about service users. DESIGN: A 2-year study,
      encompassing five cycles of participatory action research (PAR). SETTING: A small
      island community in the British Isles, adopting UK standards for pre-registration
      nurse education. METHODS: Data came from interviews with service users and
      mentors and a series of reflective group discussions with students who
      volunteered to try out the feedback mechanism. The deliberations of the PAR
      stakeholder group informed the research cycles and added to the data, which were
      subject to thematic analysis. FINDINGS: Findings indicated that service users
      volunteering to give feedback had unanimously positive experiences. Students'
      experience lay on a continuum: those with a stronger sense of self were more
      willing and able to ask for feedback than less confident students. Cultural
      adjustment to the role change needed was challenging, requiring self-awareness
      and courage. Over time, all students achieved deep learning and, for some,
      learning appeared transformative. CONCLUSION: Although contextual, the study
      concluded that the feedback initiative encouraged the development of more
      equitable relationships, in which mental health nurses respected the expertise of
      service users. This potentially benefits student development, recovery-orientated
      practice, service users and HEIs searching for meaningful ways to involve service
      users in learning and formative assessment.

PMID- 26216060
TI  - ICP monitoring in children: why are we not adhering to guidelines?
AB  - BACKGROUND: Despite pediatric guidelines, variability exists in the management of
      severe traumatic brain injury (TBI), as somewhere between 7 and 60% of children
      undergo intracranial pressure (ICP) monitoring. Reasons for this low adherence to
      TBI management guidelines remain unclear. The objective of this study was to
      evaluate the current practices at CHU Sainte-Justine with regards to ICP
      monitoring in severe TBI and explore the reasons why ICP monitoring is not
      undertaken. METHODS: A retrospective review was conducted of all patients age 1
      month to 18 years, with severe TBI (Glasgow Coma Scale (GCS) <=8) from 2007 to
      2014. Presence of ICP monitoring, head imaging reports, and reasons for lack of
      monitoring were recorded. RESULTS: Sixty-four patients with severe TBI were
      admitted. Twenty (31%) patients had invasive ICP monitoring in the first 6 h and
      5 in the following 24 h. Improvement of the GCS on arrival to tertiary care
      center (20%, n = 13) and moribund status (20%, n = 13) were the two main reasons
      ICP monitoring was not undertaken. Fourteen patients (21%) with reassuring
      cerebral tomography (Rotterdam scores 1-3) and median GCS 7 (IQR 6-8) were
      initially followed with clinical surveillance, five of which ended up with an ICP
      monitor (>6 h). CONCLUSION: Our study confirms that many children with severe TBI
      do not undergo ICP monitoring, mainly due to rapid improvement or moribund
      status. A subgroup of patients, with reassuring cerebral CT scan, was not
      monitored. Further research is necessary to assess if imaging should be
      considered in ICP indication, as in adult guidelines.

PMID- 26216062
TI  - Nurse interrupted: Development of a realistic medication administration
      simulation for undergraduate nurses.
AB  - BACKGROUND: Medication errors are a global phenomenon. Each year Australia-wide
      there are up to 96,000 preventable medication errors and in the United States
      there are approximately 450,000 preventable medication errors. One of the leading
      causes of errors is interruption yet some interruptions are unavoidable. In the
      interest of patient safety, nurses need to not only understand the impact of
      interruptions, but also be empowered with the knowledge and skills required to
      develop effective interruption management strategies. Well-planned simulation
      experiences have the potential to expose students to authentic clinical cases,
      otherwise unavailable to them, building critical thinking and clinical reasoning
      skills and preparing them for practice. AIM: This paper describes a simulated
      role-play experience that was developed to enable undergraduate nurses to
      experience, reflect on and analyse their responses to interruptions during
      medication administration. METHODS: The simulation design presented in this paper
      was underpinned by both nursing and educational theorists, in combination with
      established simulation frameworks. SETTING AND PARTICIPANTS: Embedded within a
      clinical subject in 2013, the simulation experience was run over two campuses
      within a large Australian University. Participants included 528 second year
      undergraduate nursing students and 8 academic teaching staff. OUTCOME MAPPING: To
      stimulate reflective learning debriefing immediately followed the simulation
      experience. Written reflections were completed and submitted over the following
      4weeks to extend the reflective learning process and review the impact of the
      experience from the student perspective. CONCLUSIONS: Undergraduate student
      nurses often have limited experiential background from which to draw knowledge
      and develop sound clinical judgements. Through exposure to clinical experiences
      in a safe environment, simulation technologies have been shown to create positive
      learning experiences and improve deductive reasoning and analysis. The heightened
      awareness of interruptions and their impacts on the medication administration
      process, along with techniques to manage interruptions more effectively serves to
      better prepare nurses for practice.

PMID- 26216063
TI  - Opening the conformation is a master switch for the dual localization and
      phosphatase activity of PTEN.
AB  - Tumor suppressor PTEN mainly functions at two subcellular locations, the plasma
      membrane and the nucleus. At the plasma membrane, PTEN dephosphorylates the
      tumorigenic second messenger PIP3, which drives cell proliferation and migration.
      In the nucleus, PTEN controls DNA repair and genome stability independently of
      PIP3. Whereas the concept that a conformational change regulates protein function
      through post-translational modifications has been well established in biology, it
      is unknown whether a conformational change simultaneously controls dual
      subcellular localizations of proteins. Here, we discovered that opening the
      conformation of PTEN is the crucial upstream event that determines its key dual
      localizations of this crucial tumor suppressor. We identify a critical
      conformational switch that regulates PTEN's localization. Most PTEN molecules are
      held in the cytosol in a closed conformation by intramolecular interactions
      between the C-terminal tail and core region. Dephosphorylation of the tail opens
      the conformation and exposes the membrane-binding regulatory interface in the
      core region, recruiting PTEN to the membrane. Moreover, a lysine at residue 13 is
      also exposed and when ubiquitinated, transports PTEN to the nucleus. Thus,
      opening the conformation of PTEN is a key mechanism that enhances its dual
      localization and enzymatic activity, providing a potential therapeutic strategy
      in cancer treatments. 

PMID- 26216064
TI  - Laparoscopic skill improvement after virtual reality simulator training in
      medical students as assessed by augmented reality simulator.
AB  - INTRODUCTION: Definitive assessment of laparoscopic skill improvement after
      virtual reality simulator training is best obtained during an actual operation.
      However, this is impossible in medical students. Therefore, we developed an
      alternative assessment technique using an augmented reality simulator. METHODS:
      Nineteen medical students completed a 6-week training program using a virtual
      reality simulator (LapSim). The pretest and post-test were performed using an
      object-positioning module and cholecystectomy on an augmented reality
      simulator(ProMIS). The mean performance measures between pre- and post-training
      on the LapSim were compared with a paired t-test. RESULTS: In the object
      positioning module, the execution time of the task (P < 0.001), left and right
      instrument path length (P = 0.001), and left and right instrument economy of
      movement (P < 0.001) were significantly shorter after than before the LapSim
      training. With respect to improvement in laparoscopic cholecystectomy using a
      gallbladder model, the execution time to identify, clip, and cut the cystic duct
      and cystic artery as well as the execution time to dissect the gallbladder away
      from the liver bed were both significantly shorter after than before the LapSim
      training (P = 0.01). CONCLUSIONS: Our training curriculum using a virtual reality
      simulator improved the operative skills of medical students as objectively
      evaluated by assessment using an augmented reality simulator instead of an actual
      operation. We hope that these findings help to establish an effective training
      program for medical students.

PMID- 26216065
TI  - [Repeated electrical cardioversions and amiodarone for recurrent neonatal atrial
      flutter].
AB  - Perinatal atrial flutter is a serious arrhythmia. Its management continues to
      pose a challenge during the fetal period but also, in rare intractable cases,
      during the postnatal period. This report describes the case of a neonate who
      required multiple electrical external cardioversions and amiodarone to resolve a
      recurrent atrial flutter. This case report suggests that neonatal atrial flutter
      may be recurrent at short term, that repeated electrical cardioversions with low
      energy are safe for a neonate, that amiodarone is effective as a premedication
      before cardioversion and in maintaining sinus rhythm afterward, and finally that
      the long-term prognosis is good, even when the arrhythmia is initially refractory
      to therapy. 

PMID- 26216066
TI  - [Post-herpes simplex encephalitis chorea: Viral replication or immunological
      mechanism?].
AB  - INTRODUCTION: Herpes simplex encephalitis is a severe neurological condition,
      whose outcome is improved if treated early with acyclovir. Post-herpes simplex
      encephalitis with acute chorea has rarely been reported. CASE REPORT: We report
      on two observations of children presenting with post-herpes simplex encephalitis
      with acute chorea, related to two different pathophysiological mechanisms. The
      first one is an 11-month-old girl developing relapsing herpes simplex
      encephalitis with chorea due to resumption of viral replication. The second one
      is a 2-year-old boy with relapsing post-herpes simplex encephalitis acute chorea
      caused by an immunoinflammatory mechanism. We discuss the different neurological
      presentations of herpetic relapses, notably those presenting with movement
      disorders, as well as their clinical, paraclinical, physiopathological, and
      therapeutic aspects. CONCLUSION: Post-herpes simplex encephalitis with acute
      chorea may involve two mechanisms: resumption of viral replication or an
      immunoinflammatory mechanism. Treatment of post-herpes simplex encephalitis with
      acute chorea depends on the underlying mechanism, while prevention is based on
      antiviral treatment of herpes simplex encephalitis with acyclovir at the dose of
      20mg/kg/8h for 21 days.

PMID- 26216067
TI  - Accuracy and inter-observer agreement of the ProcoreTM 25 gauge needle for
      endoscopic ultrasound-guided tissue core biopsy.
AB  - BACKGROUND: Scanty data on the performance of the new 25-gauge ProcoreTM biopsy
      needle are available. METHODS: Consecutive patients who underwent endoscopic
      ultrasound-guided fine needle biopsy (EUS-FNB) using the 25G ProcoreTM were
      retrospectively retrieved. All samples were independently reviewed by 3
      pathologists for the following: histological, cytological or no specimen,
      neoplasia, diagnostic or non-diagnostic. Diagnostic accuracy and inter-rater
      concordance among pathologists were calculated. RESULTS: 94 patients underwent
      EUS-FNB of 101 sites (69 solid masses, 25 lymph nodes, 5 wall thickening). Forty
      one biopsies (40.5%) were classified as histological samples by at least two
      pathologists, 29 as cytological (28.7%), 31 had no sample (30.7%). Good and
      almost perfect agreements among pathologists in defining cytological vs.
      histological samples (k 0.82; 95% CI: 0.74-0.90), diagnostic vs. non-diagnostic
      (k 0.95; 95% CI: 0.85-1.00) and neoplastic vs. non-neoplastic (k 0.94; 95% CI:
      0.83-1.00). According to consensus rating, 61 cases were diagnostic samples
      (60.4%). Histological samples were more likely to lead to a correct diagnosis
      (OR, 4.1; 95% P=0.027), while neoplastic lesions were less likely to be correctly
      classified than benign (OR, 0.11; P=0.04). CONCLUSIONS: EUS-FNB with the
      ProcoreTM 25G needle provided samples for histological examination in only 40% of
      the cases, with 31% of inadequate specimens, despite excellent results in term of
      inter-observer variability.

PMID- 26216068
TI  - Role of regulatory T-cells during hepatitis C infection: From the acute phase to
      post-transplantation recurrence.
AB  - Hepatitis C viral infection persists and becomes chronic in a majority of
      affected individuals. Numerous factors have been described to explain how the
      virus manages to escape the host immune system. One important escape mechanism is
      the increase in regulatory T cells induced by the virus. In this review, we will
      focus on the status of regulatory T cells throughout the natural history of
      hepatitis C infection and after liver transplantation. The molecular mechanisms
      involved in increasing the number of regulatory T cells are also discussed, as
      are data regarding the impact of regulatory T-cells on hepatic fibrosis in the
      context of hepatitis C viral infection. 

PMID- 26216069
TI  - Silicates as Latent Alkyl Radical Precursors: Visible-Light Photocatalytic
      Oxidation of Hypervalent Bis-Catecholato Silicon Compounds.
AB  - This works introduces hypervalent bis-catecholato silicon compounds as versatile
      sources of alkyl radicals upon visible-light photocatalysis. Using
      Ir[(dF(CF3)ppy)2(bpy)](PF6) (dF(CF3)ppy = 2-(2,4-difluorophenyl)-5
      trifluoromethylpyridine, bpy = bipyridine) as catalytic photooxidant, a series of
      alkyl radicals, including highly reactive primary ones can be generated and
      engaged in various intermolecular homolytic reactions. Based on cyclic
      voltammetry, Stern-Volmer studies, and supported by calculations, a mechanism
      involving a single-electron transfer from the silicate to the photoactivated
      iridium complex has been proposed. This oxidative photocatalyzed process can be
      efficiently merged with nickel-catalyzed Csp2-Csp3 cross-coupling reactions.

PMID- 26216070
TI  - Integration of Proteomics and Transcriptomics Data Sets for the Analysis of a
      Lymphoma B-Cell Line in the Context of the Chromosome-Centric Human Proteome
      Project.
AB  - A comprehensive study of the molecular active landscape of human cells can be
      undertaken to integrate two different but complementary perspectives:
      transcriptomics, and proteomics. After the genome era, proteomics has emerged as
      a powerful tool to simultaneously identify and characterize the compendium of
      thousands of different proteins active in a cell. Thus, the Chromosome-centric
      Human Proteome Project (C-HPP) is promoting a full characterization of the human
      proteome combining high-throughput proteomics with the data derived from genome
      wide expression profiling of protein-coding genes. Here we present a full
      proteomic profiling of a human lymphoma B-cell line (Ramos) performed using a
      nanoUPLC-LTQ-Orbitrap Velos proteomic platform, combined to an in-depth
      transcriptomic profiling of the same cell type. Data are available via
      ProteomeXchange with identifier PXD001933. Integration of the proteomic and
      transcriptomic data sets revealed a 94% overlap in the proteins identified by
      both -omics approaches. Moreover, functional enrichment analysis of the proteomic
      profiles showed an enrichment of several functions directly related to the
      biological and morphological characteristics of B-cells. In turn, about 30% of
      all protein-coding genes present in the whole human genome were identified as
      being expressed by the Ramos cells (stable average of 30% genes along all the
      chromosomes), revealing the size of the protein expression-set present in one
      specific human cell type. Additionally, the identification of missing proteins in
      our data sets has been reported, highlighting the power of the approach. Also, a
      comparison between neXtProt and UniProt database searches has been performed. In
      summary, our transcriptomic and proteomic experimental profiling provided a high
      coverage report of the expressed proteome from a human lymphoma B-cell type with
      a clear insight into the biological processes that characterized these cells. In
      this way, we demonstrated the usefulness of combining -omics for a comprehensive
      characterization of specific biological systems. 

PMID- 26216072
TI  - An Indigo Carmine-Based Hybrid Nanocomposite with Supramolecular Control of Dye
      Aggregation and Photobehavior.
AB  - Zn-Al layered double hydroxides (LDHs) containing solely indigo carmine (IC) or 1
      hexanesulfonate (HS) anions, or a mixture of the two with different HS/IC molar
      ratios, were prepared by the direct synthesis method and characterized by various
      techniques. Hydrotalcite-type phases were obtained with basal spacings of 17.6 A
      for the LDH intercalated by IC (IC-LDH) and 18.2-18.3 A for the other materials
      containing HS. From the basal spacing for IC-LDH and UV/Vis spectroscopic data,
      it is proposed that the dye molecules assemble within the interlayer galleries to
      form a J-type stacking arrangement. A comprehensive electronic spectral and
      photophysical study was undertaken for IC in solution and all materials, aiming
      to obtain a detailed characterization of the host-guest and guest-guest
      interactions. In solution (the solvent surrounded "isolated" molecule), IC
      presents a fast excited state proton transfer with rate constants of ~1.2
      1.4*10(11)  s(-1) , which is linked to the very efficient radiationless
      deactivation channel. In the solid state it is shown that incorporation of IC
      within the LDH decreases the level of aggregation, and that further addition of
      HS induces the appearance of isolated IC units within the LDH galleries. The
      indigo carmine-based nanocomposites reported constitute a step forward in the
      design of hybrid materials with tunable properties.

PMID- 26216071
TI  - Randomized, Multicenter Study of Gefitinib Dose-escalation in Advanced Non-small
      cell Lung Cancer Patients Achieved Stable Disease after One-month Gefitinib
      Treatment.
AB  - There is no consensus on the optimal treatment for patients with advanced non
      small-cell lung cancer (NSCLC) and stable disease (SD) after gefitinib therapy.
      This randomized, open-label, multicenter study aimed to explore whether dose
      escalation of gefitinib would improve response and survival in NSCLC patients who
      achieved SD after one-month of standard gefitinib dosage. Between May 2009 and
      January 2012, 466 patients were enrolled and 100 eligible patients were
      randomized (1:1) to receive either a higher dose (500 mg/d; H group) or to
      continue standard dose (250 mg/d; S group) of gefitinib. Objective response rate
      (ORR) was similar between the two groups (12.5% vs 12.5%, p = 1.000). There were
      no significant differences regarding progression-free survival (PFS) and overall
      survival (OS) between both arms (H group vs S group: median PFS, 5.30 months vs
      6.23 months, p = 0.167; median OS, 13.70 months vs 18.87 months, p = 0.156).
      Therefore, dose-escalation of gefitinib does not confer a response or survival
      advantage in patients who achieve SD with one month of standard-dose gefitinib
      treatment. 

PMID- 26216073
TI  - c-Fos expression correlates with performance on novel object and novel place
      recognition tests.
AB  - In rodents, many studies have been carried out using novelty-preference
      paradigms. The results show that the perirhinal cortex and the hippocampus are
      involved in the recognition of a novel object, "what", and its new position,
      "where", respectively. We employed these two variants of a novelty-preference
      paradigm to assess whether the expression of the immediate-early gene c-fos in
      the dorsal hippocampus and perirhinal cortex correlates with the performance
      discrimination ratio (d2), on the respective versions of the novelty preference
      tests. A control group (CO) was added to explore c-fos activation not specific to
      recognition. The results showed different patterns of c-Fos protein expression in
      the hippocampus and perirhinal cortex. The Where Group presented more c-Fos
      positive nuclei than the What and CO groups in the CA1 and CA3 regions, whereas
      in the perirhinal cortex, the What Group showed more c-Fos positive nuclei than
      the Where and CO groups. The correlation results indicate that levels of c-Fos in
      the CA1 area and perirhinal cortex correlate with effective exploration, d2, on
      the respective versions of the novelty preference tests, novel place and novel
      object recognition. These data suggest that the hippocampal CA1 and perirhinal
      cortex are specifically related to the level of recognition of place and objects,
      respectively. 

PMID- 26216074
TI  - Benzimidazole-functionalized ancillary ligands for heteroleptic Ru(II) complexes:
      synthesis, characterization and dye-sensitized solar cell applications.
AB  - We have designed and synthesized heteroleptic Ru(ii) complexes with a pyridine
      benzimidazole ligand (PYBI) for dye-sensitized solar cell (DSSC) applications.
      The PYBI ligand has major advantages by having the flexibility to introduce
      appropriate substituents at the four readily available positions through
      molecular engineering () compared to other ancillary bipyridyl-based ligands. We
      have substituted position A of the PYBI ligand with either electron-releasing
      triphenylamine () or pyrene (). We have also introduced 2-hexylthiophene at
      position A and 3,5-di tert-butyl phenyl group at position B of the PYBI ligand
      (). All three heteroleptic Ru(ii) complexes have been characterized by mass
      spectrometry, (1)H NMR, and absorption and emission spectroscopies as well as
      electrochemical methods. The absorption spectrum of complex is red-shifted and
      the emission spectrum is blue-shifted, when compared to the standard sensitizer.
      Testing of these newly designed heteroleptic Ru(ii) sensitizers has revealed that
      complex exhibits an efficiency of 7.88% using an I(-)/I3(-) redox electrolyte.
      Experimental observations corroborated by computational calculations have
      elucidated the high efficiency of complex , primarily due to the fact that the
      substituents at position A are more influential than those at position of B of
      the PYBI ligand. 

PMID- 26216075
TI  - Periodic hiccup in patients with subthalamic deep brain stimulation for
      Parkinson's disease.

PMID- 26216076
TI  - (3E,8E)-3,8-Bis(2-oxoindolin-3-ylidene)naphtho-[1,2-b:5,6-b']difuran-2,7(3H,8H)
      dione (INDF) based polymers for organic thin-film transistors with highly
      balanced ambipolar charge transport characteristics.
AB  - Two donor-acceptor (D-A) conjugated polymers, PINDFTT and PINDFBT, based on a
      novel electron acceptor, (3E,8E)-3,8-bis(2-oxoindolin-3-ylidene)naphtho-[1,2
      b:5,6-b']difuran-2,7(3H,8H)-dione (INDF), are synthesized for solution processed
      organic thin-film transistors. Both polymers exhibited highly balanced ambipolar
      characteristics with hole and electron mobilities up to 0.51 cm(2) V(-1) s(-1)
      and 0.50 cm(2) V(-1) s(-1), respectively. 

PMID- 26216077
TI  - The Efficacy and Safety of Concurrent Collagenase Clostridium Histolyticum
      Injections for 2 Dupuytren Contractures in the Same Hand: A Prospective,
      Multicenter Study.
AB  - PURPOSE: To evaluate efficacy and safety of concurrent administration of 2
      collagenase clostridium histolyticum (CCH) injections to treat 2 joints in the
      same hand with Dupuytren fixed flexion contractures (FFCs). METHODS: Patients
      with 2 or more contractures in the same hand caused by palpable cords
      participated in a 60-day, multicenter, open-label, phase 3b study. Two 0.58 mg
      CCH doses were injected into 1 or 2 cords in the same hand (1 injection per
      affected joint) during the same visit. Finger extension was performed
      approximately 24, 48, or 72 or more hours later. Changes in FFC and range of
      motion, incidence of clinical success (FFC <= 5 degrees ), and adverse events
      (AEs) were summarized. RESULTS: The study enrolled 715 patients (725 treated
      joint pairs), and 714 patients (724 joint pairs) were analyzed for efficacy. At
      day 31, mean total FFC (sum of 2 treated joints) decreased 74%, from 98 degrees 
      to 27 degrees . Mean total range of motion increased from 90 degrees  to 156
      degrees . The incidence of clinical success was 65% in metacarpophalangeal joints
      and 29% in proximal interphalangeal joints. Most treatment-related AEs were mild
      to moderate, resolving without intervention; the most common were swelling of
      treated extremity, contusion, and pain in extremity. The incidence of skin
      lacerations was 22% (160 of 715). Efficacy and safety were similar regardless of
      time to finger extension. CONCLUSIONS: Collagenase clostridium histolyticum can
      be used to effectively treat 2 affected joints concurrently without a greater
      risk of AEs than treatment of a single joint, with the exception of skin
      laceration. The incidence of clinical success in this study after 1 injection per
      joint was comparable to phase 3 study results after 3 or more injections per
      joint. Two concurrent CCH injections may allow more rapid overall treatment of
      multiple affected joints, and the ability to vary the time between CCH injection
      and finger extension may allow physicians and patients greater flexibility with
      scheduling treatment.

PMID- 26216078
TI  - Ulnar Head Replacement: 21 Cases; Mean Follow-Up, 7.5 Years.
AB  - PURPOSE: To report clinical and radiographic outcomes for the Herbert ulnar head
      prosthesis after a mean of 7.5 years (range, 2.0-12.5 years). METHODS: We
      performed 22 Herbert ulnar head prosthesis arthroplasties between 2000 and 2011.
      Five were primary procedures, and the remaining 17 were done after an average of
      2 (range, 1-5) previous operations. The mean age at surgery was 55 years (range,
      31-74 years). Follow-up including clinical examination, standardized
      questionnaires, and radiographic examination was done after mean 7.5 years
      (range, 2.0-12.5 years) in 21 cases. We used the Disabilities of the Arm,
      Shoulder, and Hand questionnaire, the Patient-Rated Wrist Evaluation
      questionnaire, and the Mayo wrist score questionnaire. Pain and satisfaction were
      evaluated with a 10-cm visual analog scale (VAS). Measurements of range of motion
      and strength for grip were recorded. RESULTS: Wrist range of motion was not
      affected by the arthroplasty except for supination, which significantly improved
      from 55 degrees  to 70 degrees . At follow-up, grip strength averaged 25 kg
      (range, 10-48 kg) in the operated wrists and 31 kg (range, 8-74 kg) on the
      contralateral side. Visual analog scale-pain averaged 2.9 (range, 0-8.7) during
      activity and 1.7 (range, 0-7) at rest. Satisfaction VAS was 8.9 (range, 4.3-10).
      Five patients had VAS-pain above 5 during activity, and 1 patient was
      dissatisfied and regretted having undergone arthroplasty. Mean outcomes were 27
      (range, 5-50) for Disabilities of the Arm, Shoulder, and Hand measure, 31 (range,
      0-90) for the Patient-Rated Wrist Evaluation score, and 71 (range, 30-90) for the
      Mayo wrist score. One patient was reoperated with capsuloplasty 9 months after
      the arthroplasty owing to recurrence of painful instability. Full stability was
      not achieved but the pain resolved. None of the implants showed any radiographic
      signs of loosening. CONCLUSIONS: The Herbert ulnar head prosthesis was a safe
      method of treatment and provided satisfactory midterm results for selected cases
      of distal radioulnar joint disorders. CLINICAL RELEVANCE: Increased knowledge of
      performance for ulnar head implant arthroplasty may aid surgical decision making
      for distal radioulnar joint disorders. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 26216079
TI  - The interaction of serum testosterone levels and androgen receptor CAG repeat
      polymorphism on the risk of erectile dysfunction in aging Taiwanese men.
AB  - Testosterone has been found to play important roles in men's sexual function.
      However, the effects of testosterone can be modulated by androgen receptor (AR)
      CAG repeat polymorphism. It could also contribute to the risk of erectile
      dysfunction (ED). The aim of this study is to evaluate the interaction of serum
      testosterone levels and AR CAG repeat polymorphism on the risk of ED in aging
      Taiwanese men. This cross-sectional data of Taiwanese men older than 40 years
      were collected from a free health screening held between August 2010 and August
      2011 in Kaohsiung city, Taiwan. All participants completed a health
      questionnaires included five-item version of the International Index of Erectile
      Function (IIEF-5) and the International Prostate Symptoms Score, received a
      detailed physical examination and provided 20 cm3 whole blood samples for
      biochemical and genetic evaluation. The IIEF-5 was used to evaluate ED. Serum
      albumin, total testosterone (TT), and sex hormone-binding globulin levels were
      measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism
      was determined by direct sequencing. Finally, 478 men with the mean age of 55.7
      +/- 4.8 years were included. When TT levels were above 330 ng/dL, the effect of
      testosterone level on erectile function seemed to reach a plateau and a
      significantly negative correlation between AR CAG repeat length and the score of
      IIEF-5 was found (r = -0.119, p = 0.034). After adjusting for other covariates,
      the longer AR CAG repeat length was still an independent risk factor for ED in
      subjects with TT above 330 ng/dL (p = 0.006), but not in TT of 330 ng/dL or
      below. In conclusion, both serum testosterone levels and AR CAG repeat
      polymorphism can influence erectile function concomitantly. In subjects with
      normal TT concentration, those with longer AR CAG repeat lengths have a higher
      risk of developing ED.

PMID- 26216080
TI  - Effects of high-fat diet and gastric bypass on neurons in the caudal solitary
      nucleus.
AB  - Bariatric surgery is an effective treatment for obesity that involves both
      peripheral and central mechanisms. To elucidate central pathways by which oral
      and visceral signals are influenced by high-fat diet (HFD) and Roux-en-Y gastric
      bypass (RYGB) surgery, we recorded from neurons in the caudal visceral nucleus of
      the solitary tract (cNST, N=287) and rostral gustatory NST (rNST,N=106) in rats
      maintained on a HFD and lab chow (CHOW) or CHOW alone, and subjected to either
      RYGB or sham surgery. Animals on the HFD weighed significantly more than CHOW
      rats and RYGB reversed and then blunted weight gain regardless of diet. Using
      whole-cell patch clamp recording in a brainstem slice, we determined the membrane
      properties of cNST and rNST neurons associated with diet and surgery. We could
      not detect differences in rNST neurons associated with these manipulations. In
      cNST neurons, neither the threshold for solitary tract stimulation nor the
      amplitude of evoked EPSCs at threshold varied by condition; however
      suprathreshold EPSCs were larger in HFD compared to chow-fed animals. In
      addition, a transient outward current, most likely an IA current, was increased
      with HFD and RYGB reduced this current as well as a sustained outward current.
      Interestingly, hypothalamic projecting cNST neurons preferentially express IA and
      modulate transmission of afferent signals (Bailey, '07). Thus, diet and RYGB have
      multiple effects on the cellular properties of neurons in the visceral regions of
      NST, with potential to influence inputs to forebrain feeding circuits. 

PMID- 26216081
TI  - Gingival Mesenchymal Stem Cell (GMSC) Delivery System Based on RGD-Coupled
      Alginate Hydrogel with Antimicrobial Properties: A Novel Treatment Modality for
      Peri-Implantitis.
AB  - PURPOSE: Peri-implantitis is one of the most common inflammatory complications in
      dental implantology. Similar to periodontitis, in peri-implantitis, destructive
      inflammatory changes take place in the tissues surrounding a dental implant.
      Bacterial flora at the failing implant sites resemble the pathogens in
      periodontal disease and consist of Gram-negative anaerobic bacteria including
      Aggregatibacter actinomycetemcomitans (Aa). Here we demonstrate the effectiveness
      of a silver lactate (SL)-containing RGD-coupled alginate hydrogel scaffold as a
      promising stem cell delivery vehicle with antimicrobial properties. MATERIALS AND
      METHODS: Gingival mesenchymal stem cells (GMSCs) or human bone marrow mesenchymal
      stem cells (hBMMSCs) were encapsulated in SL-loaded alginate hydrogel
      microspheres. Stem cell viability, proliferation, and osteo-differentiation
      capacity were analyzed. RESULTS: Our results showed that SL exhibited
      antimicrobial properties against Aa in a dose-dependent manner, with 0.50 mg/ml
      showing the greatest antimicrobial properties while still maintaining cell
      viability. At this concentration, SL-containing alginate hydrogel was able to
      inhibit Aa growth on the surface of Ti discs and significantly reduce the
      bacterial load in Aa suspensions. Silver ions were effectively released from the
      SL-loaded alginate microspheres for up to 2 weeks. Osteogenic differentiation of
      GMSCs and hBMMSCs encapsulated in the SL-loaded alginate microspheres were
      confirmed by the intense mineral matrix deposition and high expression of
      osteogenesis-related genes. CONCLUSION: Taken together, our findings confirm that
      GMSCs encapsulated in RGD-modified alginate hydrogel containing SL show promise
      for bone tissue engineering with antimicrobial properties against Aa bacteria in
      vitro.

PMID- 26216082
TI  - First epidemiological study on occupational radar exposure in the French Navy: a
      26-year cohort study.
AB  - This retrospective cohort study deals with the causes of death among 57,000
      military personnel who served in the French Navy surface vessels and were
      observed over the period 1975-2000. We successively compared the mortality rate
      and the specific causes of death between two groups differing in their potential
      exposure levels to radar. Occupational exposure was defined according to the on
      board workplace (radar and control groups). The age-adjusted death ratios of the
      navy personnel were compared. For all causes of death, the results showed that
      885 deaths in the radar group and 299 in the control group occurred (RR = 1.00
      (95% CI: 0.88-1.14)). RRs were 0.92 (95% CI: 0.69-1.24) for neoplasms. For the
      duration of follow-up, the results did not show an increased health risk for
      military personnel exposed to higher levels of radio frequencies in the radar
      group, but the number of deaths was very small for some cancer sites.

PMID- 26216083
TI  - Embolic Myocardial Infarction as a Consequence of Atrial Fibrillation: A
      Prevailing Disease of the Future.

PMID- 26216084
TI  - Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction
      Attributable to Coronary Artery Embolism.
AB  - BACKGROUND: Coronary artery embolism (CE) is recognized as an important
      nonatherosclerotic cause of acute myocardial infarction. Its prevalence, clinical
      features, and prognosis remain insufficiently characterized. METHODS AND RESULTS:
      We screened 1776 consecutive patients who presented with de novo acute myocardial
      infarction between 2001 and 2013. CE was diagnosed based on criteria encompassing
      histological, angiographic, and other diagnostic imaging findings. The
      prevalence, clinical characteristics, treatment strategies, in-hospital outcomes,
      and long-term risk of CE recurrence or major adverse cardiac and cerebrovascular
      events (cardiac death, fatal arrhythmia, or recurrent thromboembolism) were
      evaluated. The prevalence of CE was 2.9% (n=52), including 8 (15%) patients with
      multivessel CE. Atrial fibrillation was the most common cause (n=38, 73%). Only
      39% of patients with CE were treated with vitamin K antagonists, and the median
      international normalized ratio was 1.42 (range, 0.95-1.80). Eighteen of the 30 CE
      patients with nonvalvular atrial fibrillation had a CHADS2 score of 0 or 1. When
      those patients were reevaluated using CHA2DS2-VASc, 61% were reassigned to a
      higher risk category. During a median follow-up of 49 months, CE and
      thromboembolism recurred in 5 atrial fibrillation patients. The 5-year rate of
      major adverse cardiac and cerebrovascular events was 27.1%. In the propensity
      score-matched cohorts (n=45 each), Kaplan-Meier analysis showed a significantly
      higher incidence of cardiac death in the CE group than in the non-CE group
      (hazard ratio, 9.29; 95% confidence interval, 1.13-76.5; P<0.001). CONCLUSIONS:
      Atrial fibrillation is the most frequent cause of CE. Patients with CE represent
      a high-risk subgroup of patients with acute myocardial infarction and require
      close follow-up.

PMID- 26216086
TI  - Clinical Impact of Contemporary Cardiovascular Magnetic Resonance Imaging in
      Hypertrophic Cardiomyopathy.

PMID- 26216088
TI  - Myocardial 3-Dimensional Printing for Septal Myectomy Guidance in a Patient With
      Obstructive Hypertrophic Cardiomyopathy.

PMID- 26216089
TI  - Letter by Hernandez-Vaquero et al Regarding Article, "Saphenous Vein Graft
      Failure After Coronary Artery Bypass Surgery: Insights From PREVENT IV".

PMID- 26216085
TI  - Evaluating the Atrial Myopathy Underlying Atrial Fibrillation: Identifying the
      Arrhythmogenic and Thrombogenic Substrate.
AB  - Atrial disease or myopathy forms the substrate for atrial fibrillation (AF) and
      underlies the potential for atrial thrombus formation and subsequent stroke.
      Current diagnostic approaches in patients with AF focus on identifying clinical
      predictors with the evaluation of left atrial size by echocardiography serving as
      the sole measure specifically evaluating the atrium. Although the atrial
      substrate underlying AF is likely developing for years before the onset of AF,
      there is no current evaluation to identify the preclinical atrial myopathy.
      Atrial fibrosis is 1 component of the atrial substrate that has garnered recent
      attention based on newer MRI techniques that have been applied to visualize
      atrial fibrosis in humans with prognostic implications regarding the success of
      treatment. Advanced ECG signal processing, echocardiographic techniques, and MRI
      imaging of fibrosis and flow provide up-to-date approaches to evaluate the atrial
      myopathy underlying AF. Although thromboembolic risk is currently defined by
      clinical scores, their predictive value is mediocre. Evaluation of stasis via
      imaging and biomarkers associated with thrombogenesis may provide enhanced
      approaches to assess risk for stroke in patients with AF. Better delineation of
      the atrial myopathy that serves as the substrate for AF and thromboembolic
      complications might improve treatment outcomes. Furthermore, better delineation
      of the pathophysiologic mechanisms underlying the development of the atrial
      substrate for AF, particularly in its earlier stages, could help identify blood
      and imaging biomarkers that could be useful to assess risk for developing new
      onset AF and suggest specific pathways that could be targeted for prevention. 

PMID- 26216090
TI  - Letter by Bisleri and Muneretto Regarding Article, "Saphenous Vein Graft Failure
      After Coronary Artery Bypass Surgery: Insights From PREVENT IV".

PMID- 26216092
TI  - Correction.

PMID- 26216091
TI  - Response to Letters Regarding Article, "Saphenous Vein Graft Failure After
      Coronary Artery Bypass Surgery: Insights From PREVENT IV".

PMID- 26216093
TI  - Routine Monitoring of Liver, Renal, and Hematologic Tests After Single- or Double
      Dose Methotrexate Treatment for Ectopic Pregnancies After In Vitro Fertilization.
AB  - STUDY OBJECTIVE: To investigate the trends in liver function tests (LFTs), renal
      function tests (RFTs), and complete blood count (CBC) between day 1 and day 7
      after single- or double-dose methotrexate (MTX) treatment for sonographically
      confirmed ectopic pregnancies. DESIGN: Single center, retrospective chart review
      (Canadian Task Force classification II-3). SETTING: University-affiliated center.
      PATIENTS: All patients with a sonographically confirmed ectopic pregnancy after
      fresh in vitro fertilization-embryo transfer cycles between January 2004 and June
      2013 treated with MTX were included. INTERVENTIONS: Single- or double-dose MTX
      treatment. MEASUREMENTS AND MAIN RESULTS: LFTs, specifically alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), albumin, and total
      bilirubin levels, were measured on day of MTX administration (baseline) and 7
      days later (day 7). Similar measurements of RFTs (blood urea nitrogen [BUN] and
      creatinine) and CBC (white blood cell [WBC] and platelets) were also performed.
      The change in LFTs, RFTs, and CBC (Delta) between baseline and day 7 was
      calculated for both single- and double-dose MTX protocols. Furthermore, the
      change in LFTs, RFTs, and CBC (Delta baseline vs day 7) for single- and double
      dose MTX protocols were compared. Complete data was available for 107 patients:
      89 (83.2%) and 18 (16.8%) patients received single- and double-dose MTX
      treatment, respectively. For either single- or double-dose treatment, no
      significant difference was found between baseline and day 7 ALT, AST, albumin,
      total bilirubin, BUN, creatinine, WBC, or platelet levels after MTX treatment. A
      comparison of post-treatment changes in LFTs, RFTs, and CBC (Delta baseline vs
      day 7) also showed no difference between single- and double-dose protocols.
      CONCLUSION: Our study suggests that repeating LFTs, RFTs, or CBC on day 7 after
      single- or double-dose MTX treatment for sonographically confirmed ectopic
      pregnancies may not be necessary in patients with normal baseline testing on day
      1.

PMID- 26216094
TI  - Validation of the VBLaST: A Virtual Peg Transfer Task in Gynecologic Surgeons.
AB  - STUDY OBJECTIVE: To validate the Virtual Basic Laparoscopic Skill Trainer (VBLaST
      PT; the peg transfer task) for concurrent validity based on its ability to
      differentiate between novice, intermediate, and expert groups of gynecologists,
      and the gynecologists' subjective preference between the physical Fundamentals of
      Laparoscopic Surgery (FLS) system and the virtual reality system. DESIGN:
      Prospective study (Canadian Task Force II-2). SETTING: Academic medical center.
      PARTICIPANTS: Obstetrics and gynecology residents (n = 18) and attending
      gynecologists (n = 9). INTERVENTIONS: Twenty-seven subjects were divided into 3
      groups: novices (n = 9), intermediates (n = 9), and experts (n = 9). All subjects
      performed 10 trials of the peg transfer on each simulator. Assessment of
      laparoscopic performance was based on FLS scoring, whereas a questionnaire was
      used for subjective evaluation. MEASUREMENTS AND MAIN RESULTS: The performance
      scores in the 2 simulators were nearly identical. Experts performed better than
      intermediates and novices in both the FLS trainer and the VBLAST, and
      intermediates performed better than novices in both simulators. The results also
      show a significant learning effect on both trainers for all subgroups; however,
      the greatest learning effect was in the novice group for both trainers.
      Subjectively, 74% participants preferred the FLS over the VBLaST for training
      laparoscopic surgical skills. CONCLUSION: This study demonstrates that the peg
      transfer task was reproduced well in the VBLaST in gynecologic surgeons and
      trainees. The VBLaST has the potential to be a valuable tool in laparoscopic
      training for gynecologic surgeons.

PMID- 26216095
TI  - Effect of Intraperitoneal Bupivacaine on Postoperative Pain in the Gynecologic
      Oncology Patient.
AB  - STUDY OBJECTIVE: To evaluate if the administration of intraperitoneal bupivacaine
      decreased postoperative pain in patients undergoing minimally invasive
      gynecologic and gynecologic cancer surgery. DESIGN: Retrospective cohort study
      (Canadian Task Force classification II-3). SETTING: University-based gynecologic
      oncology practice operating at a tertiary medical center. PATIENTS: All patients
      on the gynecologic oncology service undergoing minimally invasive surgery between
      September 2011 and June 2013. INTERVENTIONS: Starting August 2012,
      intraperitoneal administration of .25% bupivacaine was added to all minimally
      invasive surgeries. These patients were compared with historical control subjects
      who had surgery between September 2011 and July 2012 but did not receive
      intraperitoneal bupivacaine. MEASUREMENTS AND MAIN RESULTS: One-hundred thirty
      patients were included in the study. The patients who received intraperitoneal
      bupivacaine had lower median narcotic use on the day of surgery and the first
      postoperative day compared with those who did not receive intraperitoneal
      bupivacaine (day 0: 7.0 mg morphine equivalents vs 11.0 mg, p = .007; day 1: .3
      mg vs 1.7 mg, p = .0002). The median patient-reported pain scores were lower on
      the day of surgery in the intraperitoneal bupivacaine group (2.7 vs 3.2, p = .05)
      CONCLUSIONS: The administration of intraperitoneal bupivacaine was associated
      with improved postoperative pain control in patients undergoing minimally
      invasive gynecologic and gynecologic cancer surgery and should be further
      evaluated in a prospective study.

PMID- 26216096
TI  - Redefining the concept of protease-activated receptors: cathepsin S evokes itch
      via activation of Mrgprs.
AB  - Sensory neurons expressing Mas-related G-protein-coupled receptors (Mrgprs)
      mediate histamine-independent itch. We show that the cysteine protease cathepsin
      S activates MrgprC11 and evokes receptor-dependent scratching in mice. In
      contrast to its activation of conventional protease-activated receptors,
      cathepsin S-mediated activation of MrgprC11 did not involve the generation of a
      tethered ligand. We demonstrate further that different cysteine proteases
      selectively activate specific mouse and human Mrgpr family members. This
      expansion of our understanding by which proteases interact with G-protein-coupled
      receptors (GPCRs) redefines the concept of what constitutes a protease-activated
      receptor. The findings also implicate proteases as ligands to members of this
      orphan receptor family while providing new insights into how cysteine proteases
      contribute to itch. 

PMID- 26216097
TI  - Whole-exome sequencing reveals a novel CHM gene mutation in a family with
      choroideremia initially diagnosed as retinitis pigmentosa.
AB  - BACKGROUND: Genomic mutations in about 200 genes are associated with hereditary
      retinal diseases. In this study, we screened for the disease-causing gene
      mutation in a family with X-linked retinal degenerative disease. METHODS:
      Pedigree data were collected and genomic DNA was isolated from peripheral blood
      of family members, who also underwent comprehensive ophthalmic examination
      including visual acuity, slit-lamp examination, fundus examination and visual
      field testing at Qilu Hospital of Shandong University. Whole-exome genomic
      sequencing was used to screen for gene mutations in the male proband. Sanger
      sequencing was used to confirm the mutation revealed in this family. RESULTS: Two
      affected males underwent ophthalmic examination; retinitis pigmentosa (RP) was
      diagnosed on the basis of night blindness beginning at an early age, decreasing
      visual acuity, progressive loss of peripheral vision, attenuation of retinal
      vessels and pigment disturbance on fundus examination. However, whole-exome
      sequencing revealed no mutation in RP-associated genes. Instead, we identified a
      novel hemizygous c.1475_1476insCA mutation in the choroideremia-associated gene
      (CHM). The mutation was confirmed by Sanger sequencing and further excluded from
      the possibility as a rare polymorphism. From the genetic data and clinical
      findings, the diagnosis was corrected to choroideremia (CHM). Further molecular
      genetic analysis suggested that this novel CHM mutation caused a frame shift
      (p.Leu492PhefsX7) and encoded a truncated nonfunctional Rab escort protein 1 (REP
      1), which caused CHM in this family. Finally, sequencing data for a pregnant
      female member confirmed that she did not carry the mutation and thus was carrying
      a healthy infant. CONCLUSION: We report a novel CHM mutation, c.1475_1476insCA,
      identified by whole-exome sequencing in a family with X-linked CHM initially
      diagnosed as RP. Our findings emphasize the value of a diagnostic approach that
      associates genetic and ophthalmologic data to facilitate the proper clinical
      diagnosis of rare hereditary retinal diseases such as CHM.

PMID- 26216098
TI  - Medicinal plants sold in the markets of Antananarivo, Madagascar.
AB  - BACKGROUND: This study focuses on the large outdoor markets of the capital of
      Madagascar, Antananarivo. As the largest metropolitan area in Madagascar with a
      population of nearly two million, the region has great capacity for consumption
      of medicinal plant remedies despite numerous pharmacies. Medicinal plant use
      spans all socioeconomic levels, and the diverse metropolitan population allows us
      to study a wide variety of people who consume these plants for medical purposes.
      The purpose of this study is to identify and generate a list of medicinal plants
      sold in the traditional markets with a focus on those collected in the forests
      around Antananarivo, get an idea of the quantities of medicinal plants sold in
      the markets around Antananarivo, and assess the economy of the medicinal plant
      markets. METHODS: In order to determine which medicinal plants are most consumed
      in Antananarivo, ethnobotanical enquiries were conducted in the five main markets
      of the capital city. Ethnobotanical surveys were conducted with medicinal plant
      traders, suppliers, harvesters and cultivators, with voucher specimens created
      from the plants discussed. Trade circuit information was established and the
      income generated by the trade of some of the species was assessed. RESULTS: The
      inventory of the Antananarivo markets resulted in a list of 89 commercialized
      plant species. Ten of the 89 were mentioned by 60-100 % of vendors. Profitability
      for vendors is high and competitive with other salaried positions within
      Antananarivo. Transportation costs are also high and therefore lower
      profitability for other members in the supply chain. CONCLUSIONS: The markets of
      Antananarivo have always played a vital cultural role in the lives of urban
      Malagasy, but our study shows they also play an economic role not only for urban
      residents but rural harvesters as well. Continued research and monitoring of the
      non-timber forest products trade in Antananarivo is needed to better understand
      the impact of trade on the wild plant populations.

PMID- 26216099
TI  - Health and wellbeing in informal caregivers and non-caregivers: a comparative
      cross-sectional study of the Swedish general population.
AB  - BACKGROUND: Informal caregiving by relatives is a great resource for individuals
      as well as for society, but the caregiving role is associated with health
      problems for the caregiver. This study aimed to compare caregivers' self-rated
      health, number of recent days with poor health and psychological wellbeing with
      that of non-caregivers in a general Swedish population. METHODS: From 2004 to
      2013, 90,845 Swedish people completed a postal questionnaire about their health,
      number of recent days with poor health during last month, psychological wellbeing
      and if they were performing caregiving or not. Descriptive statistics, chi-square
      analysis, ANOVA, logistic regressions and negative binomial regression models
      were used to investigate associations between being a caregiver or not and health
      and wellbeing. Negative binomial regression was used to assess the relation
      between caregiver status and recent days with poor health or functioning.
      RESULTS: Eleven percent reported having a caregiving role. Caregivers reported
      poorer self-rated health compared to non-caregivers, also in adjusted models;
      odds ratio (OR): 1.07 with a 95% confidence interval (CI): 1.01-1.13. Caregivers
      also reported lower psychological wellbeing compared to non-caregivers; OR: 1.22,
      CI: 1.15-1.30. Caregiving status was associated with more recent days with poor
      physical health and more recent days with poor mental health. CONCLUSIONS: This
      study suggests that caregivers have worse perceptions in self-rated health and
      psychological wellbeing compared with non-caregivers, indicating that the role of
      caregiver is adversely associated with health. This association also appears in
      terms of reporting days of poor health in the last month. The underlying
      mechanism of these associations, including the potential detrimental health
      effects of being a caregiver, needs to be investigated in longitudinal studies.

PMID- 26216100
TI  - The influence of dairy consumption, sedentary behaviour and physical activity on
      bone mass in Flemish children: a cross-sectional study.
AB  - BACKGROUND: This cross-sectional study aimed to look for an association in young
      children between whole body bone mineral content (BMC) and areal bone mineral
      density (aBMD) and dairy consumption as well as sedentary behaviour (SB) and
      physical activity (PA). Moreover, we investigated whether there was an
      interaction effect between dairy consumption and SB or PA on BMC and aBMD.
      METHODS: Healthy children (6-12 years) were recruited from primary schools. Body
      composition and whole body bone mass were measured with dual-energy X-ray
      absorptiometry (DXA), dairy consumption was assessed with a food frequency
      questionnaire (FFQ) and PA and SB with an accelerometer. In total, 272 children
      underwent a DXA scan. Complete FFQ data were available for 264 children and 210
      children had matching data from accelerometry recordings. Regression analyses
      were used to study the associations between (1) BMC and aBMD and (2) dairy
      consumption, SB and PA, adjusting for age, gender, pubertal stage, height and
      body composition. RESULTS: Dairy consumption was positively associated with whole
      body BMC and aBMD (absolute value as well as z-score), after correction for
      relevant confounders. SB was negatively associated with aBMD z-score and light PA
      was positively associated with both BMC and aBMD z-score. No gender differences
      were found. Moreover, an interaction effect between vigorous PA (VPA) and dairy
      consumption on aBMD (z-score) and BMC z-score was found, indicating that children
      with both high VPA and high dairy consumption had higher values for BMC and aBMD
      of the whole body minus the head. CONCLUSION: Already at young age, PA and dairy
      consumption positively influence whole body bone mass assessed by DXA. Moreover,
      this study indicates clearly that SB is negatively associated with whole body
      bone density. Promoting regular PA and sufficient dairy consumption in young
      children and limiting SB can be expected to positively influence their bone mass
      accumulation, which can help in the prevention of osteoporosis later in life.

PMID- 26216101
TI  - Preconditioning offers cardioprotection in hyperlipidemic rat hearts: possible
      role of Dopamine (D2) signaling.
AB  - BACKGROUND: Ischemic preconditioning (IPC) induced cardioprotection has been
      reported to be blunted in hyperlipidemic subjects. Dopamine, via its D2 receptor
      signaling, appears to mimic the signaling cascade involved in myocardial
      preconditioning and is also involved in the inhibition of hyperlipidemia induced
      mediators. The present study was designed to investigate the possible involvement
      of D2 receptors in IPC and to see whether dopamine preconditioning can offer
      cardioprotection in hyperlipidemic rat hearts. METHODS: Wistar albino rats were
      divided into 8 groups and fed on normal or high fat diet for 4 weeks.
      Hyperlipidemia was confirmed after 4 weeks by serum lipid estimations. Isolated
      perfused hearts were subjected to ischemic preconditioning or dopamine induced
      pharmacological preconditioning followed by 30-min ischemic insult and 60-min
      reperfusion. Clozapine was administered as D2 antagonist. Coronary perfusate
      (basal and post-ischemic) was collected for the estimations of LDH (Lactate
      dehydrogenase) and CKMB (Creatine kinase MB). Hearts were then removed and frozen
      for infarct size measurement. RESULTS: A significant increase body weight, serum
      lipids except HDL was noted in high fat diet fed rats, as compared to normal
      rats. The level of LDH, CKMB in coronary effluent and infarct size were found to
      be decreased in preconditioned normal hearts, as compared to hearts treated with
      ischemia reperfusion. This effect was found to be blunted in hyperlipidemic
      animals. Dopamine (10 MUM) alone and in combination with ischemic preconditioning
      significantly reduced the levels of LDH, CKMB and infarct size in hyperlipidemic
      hearts, as compared to preconditioned and non-preconditioned hyperlipidemic
      hearts. This effect was abolished significantly by Clozapine (D2 antagonist).
      CONCLUSION: The present study reveals possible involvement of D2 receptors in
      ischemic preconditioning and suggests that dopamine preconditioning may offer
      significant cardioprotection in hyperlipidemic rat hearts.

PMID- 26216102
TI  - Antibody response of definitive hosts against antigens of two life stages of the
      neuropathogenic schistosome Trichobilharzia regenti.
AB  - BACKGROUND: The nasal avian schistosome Trichobilharzia regenti spends part of
      its intravertebrate period of life within the central nervous system. Migration
      of the parasites can be accompanied by neuromotor disorders or paralysis in
      natural definitive hosts (ducks) and even in laboratory mammals. Cercariae are
      also able to penetrate human skin and induce cercarial dermatitis. While the
      cellular and antibody responses against cercariae and migrating schistosomula
      have been investigated in mice, little is known about immune reactions in birds.
      This study first describes the dynamics of antibody response in infected ducks
      and identifies frequently recognized antigens that may serve as diagnostic
      markers of infection by T. regenti. METHODS: Groups of 35 domestic ducks and 10
      mallards were exposed to different doses of T. regenti cercariae. Sera were
      collected at predefined time intervals and tested by ELISA for the presence of
      specific anti-cercarial IgY and IgM. Antigens recognized by the antibodies were
      identified on Western blots of cercariae and schistosomula. The applicability in
      immunodiagnostics was statistically evaluated by expression of specificity and
      sensitivity values for individual antigens. RESULTS: In ELISA, the levels of anti
      cercarial IgM peaked on day 15 pi. Increased production of IgY associated with
      the later phases of infection was observed in most individuals around 20 dpi and
      culminated 30 dpi. The time course of antibody response did not differ among
      experimental groups, variations were only observed in the levels of specific IgY
      which depended rather on the age of ducks at the time of infection than on the
      infectious dose. On Western blots, 40 cercarial and 7 schistosomular antigens
      were recognized by IgY from infected ducks. Among them, 4 cercarial antigens of
      50, 47, 32 and 19 kDa provided the most sensitive and specific reactions.
      CONCLUSIONS: Antigens of cercariae and schistosomula elicited distinct antibody
      response in ducks, which correlated positively with the age of animals at the
      time of infection. Several antigens originating in cercariae and fewer in
      schistosomula were recognized by IgY with diverse sensitivity and specificity;
      only a few seemed to be common to both stages. Four of them were considered as
      the most promising candidates for immunodiagnostics.

PMID- 26216103
TI  - A qualitative study of the current state of heart failure community care in
      Canada: what can we learn for the future?
AB  - BACKGROUND: In North America and other industrialized countries, heart failure
      (HF) has become a national public health priority. Studies indicate there is
      significant heterogeneity in approaches to treat and manage HF and suggest
      targeted changes in health care delivery are needed to reduce unnecessary health
      care utilization and to optimize patient outcomes. Most recent published studies
      have reported on the care of HF patients in tertiary care hospitals and the
      perspective of non-specialist stakeholders on HF management, such as general
      practitioners and clinics or hospital administrators is rarely considered. This
      study explores the current state of community-based HF care in Canada as
      experienced by various healthcare stakeholders providing or coordinating care to
      HF patients. METHODS: This study employed a qualitative exploratory research
      design consisting of semi-structured telephone interviews conducted with health
      care providers and health care administrators working outside of tertiary care in
      the four most populous Canadian provinces. A modified thematic analysis process
      was used and the different data sources were triangulated. Findings were
      collectively interpreted by the authors. RESULTS: Twenty-eight participants were
      recruited in the study: eight cardiologists, five general practitioners/family
      physicians, eight nurse practitioners/registered nurses, four hospital
      pharmacists and three health care administrators/directors. Participants reported
      a lack of stakeholder engagement throughout the continuum of care, which hinders
      the implementation of a coordinated approach to quality HF care. Four substantive
      themes emerged that indicated challenges and gaps in the optimal treatment and
      management of HF in community settings: 1) challenges in the risk assessment and
      early diagnosis of HF, 2) challenges in ensuring efficient and consistent
      transition from acute care setting to the community, 3) challenges of primary
      care providers to optimally treat and manage HF patients, and 4) challenges in
      promoting a holistic approach in HF management. CONCLUSIONS: As health systems
      evolve from tertiary-based care to community-based outpatient services for the
      management of chronic diseases, this study's findings pinpoint challenges that
      have been observed in the Canadian context and can stimulate and orient dialogue
      toward solutions for a more coordinated approach to improve the care of HF
      patients and reduce pressure on the healthcare system.

PMID- 26216104
TI  - Labral morphologic characteristics in patients with symptomatic acetabular
      dysplasia.
AB  - BACKGROUND: The morphologic characteristics of the labrum in patients with
      symptomatic acetabular dysplasia have been described to some extent in smaller
      retrospective series, but the need remains to further define these disease
      characteristics and their importance as a diagnostic feature of hip instability.
      PURPOSE: To (1) characterize the morphologic characteristics of the labrum in
      patients with symptomatic acetabular dysplasia and (2) test the relationships
      between specific labral variants, severity of dysplasia, and duration of
      symptoms. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS:
      Thirteen surgeons from 10 centers enrolled patients undergoing periacetabular
      osteotomy (PAO) for symptomatic acetabular dysplasia from 2008 to 2014. Patient
      demographics, presenting characteristics, preoperative radiographic data,
      operative data, and intraoperative findings were prospectively collected and
      retrospectively reviewed. RESULTS: A total of 942 patients (972 hips) met the
      initial inclusion criteria, with a mean age of 25.2 years (range, 9-51 years; 84%
      female, 16% male). In addition to having PAO, 52.6% of hips had an anterior
      arthrotomy and 19.8% had a hip arthroscopy either to perform an
      osteochondroplasty of the femoral head-neck junction or to address labral
      pathologic changes. Of these 553 hips in which the labrum was visualized, labral
      morphologic status was graded as hypertrophic in 50%, normal in 45%, hypoplastic
      in 4%, and ossified in less than 1%. Decreased lateral center-edge angle and
      anterior center-edge angle and increased acetabular inclination were associated
      with labral hypertrophy, but chronicity of symptoms was not. Of the 553 hips, 64%
      had tears of the labrum, with the majority being degenerative-type tears.
      CONCLUSION: Labral pathologic changes are common in patients with symptomatic
      acetabular dysplasia. Labral hypertrophy, however, is not a universal finding,
      particularly in hips with mild dysplasia, and therefore should not be considered
      a reliable diagnostic criterion for instability.

PMID- 26216105
TI  - Detrimental Effect of Repeated and Single Subacromial Corticosteroid Injections
      on the Intact and Injured Rotator Cuff: A Biomechanical and Imaging Study in
      Rats.
AB  - BACKGROUND: The effect of corticosteroids on tendons is poorly understood, and
      current data are insufficient and conflicting. PURPOSE: To evaluate the effects
      of corticosteroid injections on intact and injured rotator cuffs (RCs) through
      biomechanical and radiographic analyses in a rat model. STUDY DESIGN: Controlled
      laboratory study. METHODS: A total of 70 rats were assigned to 7 groups.
      Uninjured rats (no tear) received either a single saline injection, a single
      methylprednisolone acetate (MTA) injection, or triple MTA injections. Injured
      rats (unilateral supraspinatus injury) received either a single saline injection,
      triple saline injections, a single MTA injection, or triple MTA injections
      (injections were subacromial; repeat injections were administered weekly). Rats
      were sacrificed 1 week after final injection. Shoulders were harvested and
      grossly inspected, and the supraspinatus tendon was evaluated biomechanically.
      Bone density at the tendon insertion site on the greater tuberosity was assessed
      by micro-computed tomography. RESULTS: Intact RCs exposed to triple MTA
      injections had significantly decreased maximal load and stiffness compared with
      the control group (14.43 vs 21.25 N and 8.21 vs 16.6 N/mm, respectively; P <
      .05). Injured RCs exposed to steroid treatment had significantly lower maximal
      load (single saline: 10.91 N, single steroid: 8.43 N [P < .05]; triple control:
      15.77 N, triple steroid: 11.65 N [P < .05]) compared with the control at 3 weeks.
      Greater tuberosity volume density and connectivity density were significantly
      lower in undamaged rats after triple MTA injection (P < .05). CONCLUSION: The
      study results clearly showed that repeated doses of corticosteroids significantly
      weaken rat RC and negatively affect bone quality in addition to possibly causing
      deterioration of the osteotendinous junction. However, data retrieved from
      animals must be scrupulously analyzed before extrapolation to humans. As such,
      the potential benefits and harms of subacromial corticosteroid treatment must be
      considered before administration. CLINICAL RELEVANCE: The potential benefit and
      detrimental effects of corticosteroid injection should be thoroughly considered
      before it is administered subacromially in patients with RC injuries.

PMID- 26216106
TI  - Synthesis of deuterium-labeled hydroxybupropion.
AB  - This paper describes the synthesis of deuterium-labeled hydroxybupropion. Mass
      spectrometry analysis of the compound revealed over 98% deuterium enrichment. 

PMID- 26216107
TI  - Renal Denervation for the Treatment of Hypertension: Making a New Start, Getting
      It Right.

PMID- 26216109
TI  - Enlarging the substrate portfolio of the thermophilic esterase EST2 from
      Alicyclobacillus acidocaldarius.
AB  - The enzymatic regioselective hydrolysis of (a) acetylated mono- to
      tetrasaccharides of different nature, (b) of acetylated aryl glycosides and (c)
      of different acetylated nucleosides was studied enlarging the portfolio of
      substrates that can be employed by the thermophilic esterase EST2 from
      Alicyclobacillus acidocaldarius. The reactions were optimised to the extent that
      the amount of enzyme needed was lowered of two orders of magnitude with respect
      to the previously reported reactions, namely from 4000 to 40 U of enzyme per
      reaction. New additional solvents were screened and dramatic changes in
      regioselectivity were observed depending on the amount and type of solvent used.
      For example, in the presence of 10 % DMF, only two alpha-D-glucose products 6-OH
      and 4,6-OH (in a 76:24 ratio) were detected, whereas with 25 % DMF, at least four
      products of similar amount were observed. This versatility adds specific value to
      the biocatalyst making possible the design of biocatalytic reactions with
      different hydrophobic ester substrates. As an additional remarkable example, EST2
      catalysed with a good yield and high regioselectivity the hydrolysis of p
      nitrophenyl beta-D-xylopyranoside triacetate producing only the monoacetylated
      derivative with acetyl group in 3-O-position, in 2 min. The results with
      nucleosides as substrates are particularly interesting. The peracetates of 3',5'
      di-O-acetylthymidine are converted almost quantitatively (95 %) to the
      monoacetylated derivative possessing free secondary OH; this regioselectivity is
      complementary to hydrolysis/alcoholysis reactions catalysed by CAL-B lipase or to
      other microbial hydrolytic biocatalysts, generally giving products with free
      primary OH groups. A docking analysis was undertaken with all analysed substrates
      suggesting a structural interpretation of the results. In most of cases, the best
      pose of the selected substrate was in line with the observed regioselectivity.

PMID- 26216108
TI  - Extracellular peptidases from Deinococcus radiodurans.
AB  - The extremophile Deinococcus radiodurans wild type R1 produces peptidases
      (metallo- and serine-) in TGY medium and in the media supplemented with human
      hair (HMY) and chicken feathers (FMY). Enzymatic screening on agar plates
      revealed peptidase activity. In TGY medium metallopeptidases were detected
      corresponding to a molecular mass range of 300-85 kDa (gelatinases); 280-130
      (caseinases) and a 300 and a 170 kDa (keratinases); and a gelatinolytic serine
      peptidase (75 kDa). In HMY medium after 144 h, D. radiodurans produced keratinase
      (290 U/ml), gelatinase (619 U/ml) and sulfite (26 ug/ml). TGY medium produced
      higher proteolytic activity: 950 U/ml of gelatinolytic (24 h); 470 U/ml of
      keratinolytic (24 h) and 110 U/ml of caseinolytic (72 h). In the FMY medium, we
      found gelatinolytic (317 U/ml), keratinolytic (43 U/ml) and caseinolytic (85
      U/ml) activities. The sulfite had a maximum release at 48 h (8.1 ug/ml).
      Enzymography analysis revealed that the keratinases degraded keratin after 24 h
      of reaction. The addition of sodium sulfite (1.0 %) improved the keratin
      degradation. Environmental Scanning Electron microscopy revealed alterations such
      as damage and holes in the hair fiber cuticle after D. radiodurans growth. This
      work presents for the first time D. radiodurans as a new keratinolytic
      microorganism.

PMID- 26216110
TI  - HIV/AIDS Knowledge, Self-Efficacy for Limiting Sexual Risk Behavior and Parental
      Monitoring.
AB  - The purpose of this study was to explore HIV/AIDS knowledge, self-efficacy for
      sexual risk behaviors, and parental monitoring in a sample of 140 7th and 9th
      grade adolescents studying in an urban high school in the United States. Further,
      the study examined differences in HIV/AIDS knowledge, self-efficacy and parental
      monitoring by grade and gender. This study also investigated the effectiveness of
      an HIV/AIDS peer education program, Teens for AIDS Prevention (TAP), on improving
      adolescents' HIV/AIDS knowledge. A quasi-experimental design was used to examine
      effects of the peer education program (TAP) on adolescents' HIV/AIDS knowledge.
      Pearson-product-moment correlation coefficients were calculated to examine the
      relationships among the variables. Independent t-tests were used to compare
      adolescents' HIV/AIDS knowledge, self-efficacy, and parental monitoring scores by
      grade and gender. Paired t-tests were used to determine differences in pre
      intervention and post-intervention HIV/AIDS knowledge. The results showed that
      HIV/AIDS knowledge improved significantly in both 7th and 9th grade students
      after the intervention. HIV/AIDS knowledge was associated with self-efficacy;
      however it was not associated with parental monitoring. There were no significant
      differences in HIV/AIDS knowledge and self-efficacy by gender. However, there was
      a significant difference in parental monitoring by gender. Pediatric nurses are
      well-positioned to develop and implement evidence-based programs for adolescents.
      It is essential that pediatric nurses, in conjunction with other professionals
      and parent groups, take the initiative in implementing peer education programs in
      schools and community centers to promote healthy behaviors among adolescents. 

PMID- 26216111
TI  - Neurogenesis and neuroprotection in postischemic brain neurodegeneration with
      Alzheimer phenotype: is there a role for curcumin?
AB  - For thousands of years, humankind has used plants for therapeutics. Nowadays,
      there is a renewed public interest in naturally occurring treatments with minimal
      toxicity and diets related to health. Alterations in hippocampal neurogenesis
      have been recognized as an integral part of brain ischemia. Neuronal
      stem/progenitor cells in the hippocampus are positively and negatively regulated
      by intrinsic and extrinsic agents. One positive regulator of neurogenesis in the
      hippocampus is curcumin in the diet. This review provides an assessment of the
      current state of the field in hippocampal neurogenesis and neuroprotection
      studies in brain ischemia and focuses on the role of curcumin in the diet. Data
      suggest that dietary intake of curcumin enhances neurogenesis. Recent studies
      performed in ischemic models have suggested that curcumin also has
      neuroprotective features. One potential mechanism to explain several of the
      general health benefits associated with curcumin is that it may prevent ageing
      associated changes in cellular proteins that lead to protein insolubility and
      aggregation after ischemia such as beta-amyloid peptide and tau protein. Here, we
      also review the evidence from ischemic models that curcumin improves cognition
      and health span by overexpression of life supporting genes and preventing or
      delaying the onset of neurodegenerative changes. Available data provide evidence
      that curcumin induces neurogenesis and neuroprotection and may provide a novel
      therapeutic agent for both regenerative medicine and for the treatment of
      neurodegenerative diseases such as postischemic brain neurodegeneration with
      Alzheimer phenotype. 

PMID- 26216112
TI  - Age-related dendritic and spinal alterations of pyramidal cells of the human
      visual cortex.
AB  - INTRODUCTION: Normal aging is characterized by deterioration of visual abilities,
      affecting mainly visual acuity, contrast and wavelength sensitivity. In the
      present study we attempted to describe the morphological and morphometric
      alterations of the dendrites and the dendritic spines of the pyramidal cells of
      the visual cortex during normal aging, in order to approach the visual impairment
      of aged individuals from a neuropathological point of view. MATERIAL AND METHODS:
      We studied the visual cortex in 20 brains using the Golgi technique. RESULTS: In
      pyramidal cells, which represent the majority of cortical neurons, age-related
      pathology can be observed in cell somata as well as, most importantly, in
      dendrite number and morphology. The apical dendrites of some pyramidal cells are
      distorted and tortuous. Horizontal dendritic arborization is also severely
      decreased. These alterations were more prominent in the corticocortical pyramidal
      neurons of the 5th layer. CONCLUSIONS: The morphological and morphometric
      assessment of the dendrites and the dendritic spines in the visual cortex in
      normal aging revealed substantial alterations of the dendritic arborization and
      marked loss of the dendritic spines, which may be related to visual impairment
      even in normal aging.

PMID- 26216113
TI  - IgG4-related inflammatory orbital pseudotumors - a retrospective case series.
AB  - Orbital diseases may be divided into congenital defects of the orbit, infectious
      and inflammatory diseases, orbital tumors (including malignant and benign tumors)
      and injuries. Idiopathic inflammatory syndromes are often encountered within the
      orbit and are usually classified as orbital pseudotumors. The etiology of
      pseudotumors of the vision organ is unknown. Infectious agents, autoimmune
      disorders and improper healing are taken into consideration in the pathogenesis
      of this disorder. Thanks to detailed studies conducted in recent years, a new
      disease syndrome was identified in 2001. It is known as IgG4-related disease, and
      its differentiation is based on the analysis of IgG4 levels in the affected
      tissues. Orbital locations of the disease were first reported in Japan as late as
      at the end of 2009. This finding triggered the European studies on this subject.
      To date, no such studies have been conducted in Poland. The starting study
      population consisted of 167 patients with isolated infiltrative tumor diseases
      within the orbital region treated at the Department of Otolaryngology, Head and
      Neck Surgery of the Medical College Jagiellonian University in Krakow. Detailed
      analysis and diagnostic screening for IgG4-related disease was performed in a
      total of 17 patients diagnosed with orbital pseudotumor. 

PMID- 26216114
TI  - Analysis of intracranial volume ratios by means of cerebrospinal fluid deployment
      indicators.
AB  - INTRODUCTION: Imaging studies make it possible not only to visualize the general
      structure of the brain but also to take precise measurements of brain tissue
      volume and the size of individual lobes and their structure. The aim of this
      study was to determine the ratio of cerebrospinal fluid (CSF) volume contained in
      the intracranial ventricular system to the brain tissue volume and the ratio of
      CSF volume in the subarachnoid space and basal cisterns to the brain tissue
      volume. MATERIAL AND METHODS: The evaluation of volumetric measurements of
      computed tomographic (CT) images was undertaken on 23 male and female patients
      (average age 56.9 +/- 6.1) diagnosed with normal pressure hydrocephalus (NPH) and
      27 male and female patients (average age 70.6 +/- 5.2) diagnosed with brain
      atrophy (BA). In the CT imaging studies, the total brain tissue volume and CSF
      volume collected in the intracranial fluid cavities were mapped to a colour
      scale. The VisNow software was used for volumetric evaluation. The groups were
      compared by means of the non-parametric Kolmogorov-Smirnov test (K-S) for
      independent samples. Paired data were compared by means of the nonparametric
      Wilcoxon test. RESULTS: The volumes of brain (brain volume - BV) and
      cerebrospinal fluid (fluid volume - FV) differ greatly from each other in both
      groups BA and NPH. The SBR (subarachnoid space and basal cisterns-to-brain ratio)
      and VBR (ventricle-to-brain ratio) indicators differ significantly and very much
      within the NPH group as well as within the BA group. In the NPH group a clearly
      higher value of VBR can be observed in comparison with the BA group. There was a
      higher value of SBR in the BA than the NPH group. CONCLUSIONS: The simultaneous
      use of two indicators, VBR and SBR, on a study group of 50 patients enabled the
      total separation of NPH and BA groups. This differentiation can have real
      diagnostic value. Thus the volumetric assessment of the volume of CSF and brain
      tissue based on CT of the head can become an important part of the differential
      diagnosis of hydrocephalus and brain atrophy.

PMID- 26216115
TI  - Effect of oral administration of pig spinal cord hydrolysate on clinical and
      histopathological symptoms of experimental allergic encephalomyelitis in rats.
AB  - Oral tolerance is the natural occurring phenomenon of a decreased immune response
      to previously fed antigens, which prevents induction of a response to dietary
      antigens. One of the mechanisms is deletion of T lymphocytes reactive to the fed
      antigen. Knowing that phenomenon, it seems appropriate to engage this mechanism
      for treatment of autoimmune diseases. Multiple sclerosis (MS) is an
      autoimmunological disease which causes neurological impairment in humans.
      Autoreactive T lymphocytes migrate through the open blood-brain barrier into the
      central nervous system (CNS), where they recognize myelin antigens as foreign,
      and induce an inflammatory response against the myelin sheath, which causes
      demyelination and even axonal loss. Experimental allergic encephalomyelitis
      (EAE), an animal model of MS, resembles the autoimmunological aspect of the
      disease. We used a broad spectrum of myelin antigens to induce EAE, and also to
      induce oral tolerance by giving myelin epitopes intragastrically to rats. The aim
      of our study was to evaluate whether pig spinal cord hydrolysate given
      intragastrically is able to evoke oral tolerance in rats with an animal model of
      MS - EAE. In our experiments we fed female Lewis rats with pig spinal cord
      hydrolysate at doses of 5, 20 and 100 mg per kg of body weight. We observed
      diminished clinical symptoms of ongoing EAE in rats fed with all doses of pig
      spinal cord hydrolysate. In the histopathological study, intensity of the
      inflammatory process in spinal cord was similar in rats not fed with EAE and in
      rats fed with lower doses of pig spinal cord hydrolysate. In animals fed with the
      highest dose of pig spinal cord hydrolysate, intensification of the inflammatory
      response was observed. These results were confirmed by morphometric evaluations.
      We found that feeding animals with preparations containing myelin antigens can
      reduce EAE symptoms, which may indicate oral tolerance induction, but the
      obtained results also underline the importance of dose of the orally given
      antigens, because of the possibility of enhancement of the inflammatory process
      in the CNS. 

PMID- 26216116
TI  - Increased nitric oxide levels in cerebellum of cachectic rats with Walker 256
      solid tumor.
AB  - In cancer cachexia, the role of nitric oxide (NO) in the central nervous system
      remains unclear. Cerebellar degeneration has been reported in cancer patients,
      but the participation of NO has not been studied. Thus, this study investigated
      the mechanism of oxidative cerebellar injury in a time-course cancer cachexia
      experimental model. The cachexia index is progressive and evident during the
      evolution of the tumor. Nitric oxide and lipid hydroperoxidation quantification
      was performed using a very sensitive and precise chemiluminescence method, which
      showed that both analyzed parameters were increased after tumor implantation. In
      the day 5 group, NO was significantly increased, and this experimental time was
      chosen to treat the rats with the NO inhibitors N-nitro-L-arginine methyl ester
      (L-NAME) and aminoguanidine (AG). When treated with NO inhibitors, a significant
      decrease in both NO and lipid hydroperoxide levels occurred in the cerebellum. 3
      nitrotyrosine was also analyzed in cerebellar tissue by immunohistochemistry; it
      was increased at the three experimental time points studied, and decreased when
      treated with L-NAME and AG. Besides demonstrating that lipid hydroperoxidation in
      the cerebellum of rats with cachexia increases in a time-dependent manner, this
      study is the first to describe the participation of NO and its oxidized product 3
      NT in the cerebellum of cachectic rats bearing the Walker 256 solid tumor. 

PMID- 26216117
TI  - Administration of leukemia inhibitory factor increases Opalin and myelin
      oligodendrocyte glycoprotein expression in the cerebral cortex in a cuprizone
      induced model of demyelination.
AB  - Multiple sclerosis (MS) lesions are characterized by inflammatory demyelination
      and reactive gliosis, and although remyelination occurs in some lesions it is
      limited and incomplete. Leukemia inhibitory factor (LIF) is an important cytokine
      that stimulates oligodendrocyte proliferation and survival in vitro. Opalin is a
      unique molecular marker for mature oligodendrocytes. The aim of this study was to
      demonstrate the role of LIF on Opalin and myelin oligodendrocyte glycoprotein
      (MOG) expression in the cerebral cortex of cuprizone-induced MS mice. The mice
      were treated with cuprizone for five weeks in order to induce MS. The mice were
      then divided into 3 groups. The first group was injected intraperitoneally (IP)
      with LIF for six weeks in the amount of 30 ug/kg bw per day. The second group
      (SHAM) was injected IP with normal saline and the third group was left without
      injection as a control. After six weeks the mice were killed, the cerebral cortex
      was harvested, and the expression of MOG and Opalin was studied. Using western
      blotting we found that LIF increases Opalin and MOG expression in the cerebral
      cortex extracts as compared to SHAM and control groups. However, no significant
      difference in the Opalin and MOG expression was seen between SHAM and control
      groups. It is concluded that LIF may have an important role in the process of
      remyelination by increasing Opalin expression and MOG expression. 

PMID- 26216118
TI  - Adult, isolated respiratory chain complex IV deficiency with minimal
      manifestations.
AB  - OBJECTIVES: Isolated complex IV (cytochrome c oxidase) deficiency is one of the
      most frequent respiratory chain defects in mitochondrial disorders (MIDs) and
      usually occurs together with severe pediatric or rarely adult multisystem
      disease. Here we report an adult with isolated complex IV deficiency with
      unusually mild clinical manifestations. CASE REPORT: A 50-year-old man had
      developed generalized muscle aches and occasional twitching and stiffness of the
      musculature since age 48 years. He had a previous history of diabetes, acute
      hearing loss, hyperlipidemia, hyperuricemia, arterial hypertension,
      polyarthrosis, hypogonadism, and hypothyroidism. The family history was positive
      for diabetes (mother), CK elevation (brother), myalgias (brother), and proximal
      weakness of the upper limbs (mother). Work-up revealed hypoacusis, postural
      tremor and reduced tendon reflexes, recurrent mild hyper-CK-emia, neurogenic
      needle electromyography, and a muscle biopsy with mild non-specific changes.
      Biochemical investigations of the muscle homogenate revealed an isolated complex
      IV defect and reduced amounts of coenzyme Q (CoQ). He profited from CoQ
      supplementation, low-carbohydrate diet, and gluten-free diet. CONCLUSIONS:
      Isolated complex IV deficiency may present with only mild muscular, endocrine, or
      cardiac manifestations in adults. Coenzyme Q supplementation, low-carbohydrate
      diet, and gluten-free diet may have a beneficial effect at least on some of the
      manifestations.

PMID- 26216119
TI  - Multiple schwannomas of the digital nerves and superficial radial nerve: two
      unusual cases of segmental schwannomatosis.
AB  - Two cases of segmental sporadic schwannomatosis characterized by unusual location
      of multiple schwannomas in digital nerves (case 1) and the superficial radial
      nerve (case 2) are described in this paper. In the first of the described cases,
      6 tumours located at the base of the middle finger and in its distal portion were
      excised from both digital nerves. In the second case, 3 tumours located in the
      proximal 1/3 and halfway down the forearm were removed from the superficial
      radial nerve. In both cases, symptoms such as palpable tumour mass, pain,
      paraesthesias, and positive Tinel-Hoffman sign resolved after operative
      treatment. Final diagnoses were made based on histopathological examination
      results. In the second of the described cases, the largest of the excised lesions
      had features enabling diagnosis of a rare tumour type - ancient schwannoma. 

PMID- 26216120
TI  - Are granular osmiophilic material deposits an epiphenomenon in CADASIL?
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene.
      Pathophysiologically, there seems to be multimerization of the extracellular
      domain of the protein with a possible gain of function on vascular smooth
      muscular cells. However, the mechanisms and determinants of NOTCH3
      multimerization are not completely understood, and it is not completely
      elucidated whether NOTCH3 multimerization contributes to the appearance of
      granular osmiophilic material (GOM) deposits, which are the pathological hallmark
      of CADASIL. We recently reported a patient with parkinsonism and cognitive
      impairment and with evidence of diffuse white matter changes on imaging, carrying
      a NOTCH3 nonsense mutation in exon 3 (c.307C>T), and suggested that such a
      hypomorphic NOTCH3 mutation was likely to be pathogenic. We further pursued
      ultrastructural examination of skin vessels in our case, and here we report the
      results, wishing to make a comment on whether GOM deposits should be considered
      the pathological hallmark for a definitive diagnosis of CADASIL in those patients
      whose mutations are predicted in the production of hypomorphic protein products. 

PMID- 26216121
TI  - Liquid sensor based on a piezoelectric lateral electric field-excited resonator.
AB  - The influence of viscous and conducting liquid on the characteristics of a
      piezoelectric lateral electric field-excited resonator based on the X-cut lithium
      niobate plate has been investigated. It has been found that the contact of a free
      surface of such resonator with conducting or viscous liquid leads to the
      substantial variation of its electrical impedance/admittance. The analysis has
      shown the modulus of electrical impedance or admittance at any frequency near the
      parallel or series resonance to be a parameter unambiguously associated with the
      conductivity or the viscosity. This parameter is more sensitive to the variation
      of the liquid conductivity or viscosity as compared to the widely used for this
      purpose resonant frequency whose variation area is essentially smaller. By this
      means the liquid conductivity and viscosity affects unambiguously on the change
      of electrical impedance and admittance modulus whose measurement at a fixed
      frequency should present no problem in practice. Consequently, the lateral field
      excited resonator we have described may be employed as a liquid conductivity and
      viscosity meter with an appropriate graduation. 

PMID- 26216122
TI  - Acoustical cross-talk in row-column addressed 2-D transducer arrays for
      ultrasound imaging.
AB  - The acoustical cross-talk in row-column addressed 2-D transducer arrays for
      volumetric ultrasound imaging is investigated. Experimental results from a 2.7
      MHz, lambda/2-pitch capacitive micromachined ultrasonic transducer (CMUT) array
      with 62 rows and 62 columns are presented and analyzed in the frequency
      wavenumber domain. The sources of cross-talk are identified and predicted
      theoretically. The nearest neighbor cross-talk is -23.9+/-3.7 dB when the array
      is used as a 1-D array with the rows functioning as both transmitters and
      receivers. In the row-column configuration, with the columns transmitting and the
      rows receiving, the cross-talk is reduced to -40.2+/-3.5 dB.

PMID- 26216123
TI  - Skin-resident memory CD4+ T cells enhance protection against Leishmania major
      infection.
AB  - Leishmaniasis causes a significant disease burden worldwide. Although Leishmania
      infected patients become refractory to reinfection after disease resolution,
      effective immune protection has not yet been achieved by human vaccines. Although
      circulating Leishmania-specific T cells are known to play a critical role in
      immunity, the role of memory T cells present in peripheral tissues has not been
      explored. Here, we identify a population of skin-resident Leishmania-specific
      memory CD4+ T cells. These cells produce IFN-gamma and remain resident in the
      skin when transplanted by skin graft onto naive mice. They function to recruit
      circulating T cells to the skin in a CXCR3-dependent manner, resulting in better
      control of the parasites. Our findings are the first to demonstrate that CD4+ TRM
      cells form in response to a parasitic infection, and indicate that optimal
      protective immunity to Leishmania, and thus the success of a vaccine, may depend
      on generating both circulating and skin-resident memory T cells.

PMID- 26216124
TI  - CD68 acts as a major gateway for malaria sporozoite liver infection.
AB  - After being delivered by the bite from an infected mosquito, Plasmodium
      sporozoites enter the blood circulation and infect the liver. Previous evidence
      suggests that Kupffer cells, a macrophage-like component of the liver blood
      vessel lining, are traversed by sporozoites to initiate liver invasion. However,
      the molecular determinants of sporozoite-Kupffer cell interactions are unknown.
      Understanding the molecular basis for this specific recognition may lead to novel
      therapeutic strategies to control malaria. Using a phage display library screen,
      we identified a peptide, P39, that strongly binds to the Kupffer cell surface
      and, importantly, inhibits sporozoite Kupffer cell entry. Furthermore, we
      determined that P39 binds to CD68, a putative receptor for sporozoite invasion of
      Kupffer cells that acts as a gateway for malaria infection of the liver. 

PMID- 26216125
TI  - Functional IRF3 deficiency in a patient with herpes simplex encephalitis.
AB  - Herpes simplex encephalitis (HSE) in children has previously been linked to
      defects in type I interferon (IFN) production downstream of Toll-like receptor 3.
      Here, we describe a novel genetic etiology of HSE by identifying a heterozygous
      loss-of-function mutation in the IFN regulatory factor 3 (IRF3) gene, leading to
      autosomal dominant (AD) IRF3 deficiency by haploinsufficiency, in an adolescent
      female patient with HSE. IRF3 is activated by most pattern recognition receptors
      recognizing viral infections and plays an essential role in induction of type I
      IFN. The identified IRF3 R285Q amino acid substitution results in impaired IFN
      responses to HSV-1 infection and particularly impairs signaling through the TLR3
      TRIF pathway. In addition, the R285Q mutant of IRF3 fails to become
      phosphorylated at S386 and undergo dimerization, and thus has impaired ability to
      activate transcription. Finally, transduction with WT IRF3 rescues the ability of
      patient fibroblasts to express IFN in response to HSV-1 infection. The
      identification of IRF3 deficiency in HSE provides the first description of a
      defect in an IFN-regulating transcription factor conferring increased
      susceptibility to a viral infection in the CNS in humans. 

PMID- 26216127
TI  - Peroxisome Proliferator-Activated Receptor-gamma and Its Ligands in the Treatment
      of Tumors in the Nervous System.
AB  - The peroxisome proliferator-activated receptor -gamma (PPARgamma) has been
      identified in a wide range of cancers, including brain, breast, colon, stomach
      and lung cancers. It belongs to the thyroid/ steroid hormone receptors
      superfamily. Binding with their special ligands, PPARgamma plays important roles
      in regulating transcription of their target genes. PPARgamma activation
      suppresses the growth of the tumor cells, implicating the anti-tumor potential of
      PPARgamma ligand. Tumors in the nervous system are among the most devastating
      cancers. This review highlights key advances in understanding the effects of
      PPARgamma ligands in the treatment of tumors in the nervous system. 

PMID- 26216128
TI  - Management of Inflammatory Bowel Disease Using Stem Cell Therapy.
AB  - Inflammatory bowel diseases (IBD are a collection of diseases associated with
      chronic inflammation in the intestinal mucosa and/or transmural involvement. IBD
      is divided into two main categories Crohn's disease (CD and ulcerative colitis
      (UC. While there is no cure for IBD, current therapies can only reduce the
      inflammatory process that causes the signs and symptoms of IBD and hopefully
      induce long-term remission. Improved treatment modalities for the complex IBD are
      still evolving. The increased understanding of the underlying immunopathology has
      helped identify new targeted treatment options in particular the use of stem cell
      treatments that are capable of modulating the immune system. Haematopoietic stem
      cells (HSC and mesenchymal stromal cells (MSC therapy are both being investigated
      as a treatment for IBD. MSC therapy is well tolerated and associated with minimal
      established side-effects compared to HSC therapy, which involves ablative
      chemotherapy. Currently, such stem cell therapy is not a standard of care regimen
      for IBD. However, it may potentially become the next generation treatment of
      choice, especially for severe refractory IBD patients. 

PMID- 26216126
TI  - Non-HIV-related health care utilization, demographic, clinical and laboratory
      factors associated with time to initial retention in HIV care among HIV-positive
      individuals linked to HIV care.
AB  - OBJECTIVES: The aim of the study was to explore non-HIV-related health care
      service (NHRHS) utilization, demographic, clinical and laboratory factors
      associated with timely initial "retention" in HIV care among individuals "linked"
      to HIV care in British Columbia (BC), Canada. METHODS: We conducted a Weibull
      time-to-initial-retention analysis among BC Seek and Treat for Optimal Prevention
      of HIV/AIDS (STOP HIV/AIDS) cohort participants linked in 2000-2010, who had >= 1
      year of follow-up. We defined "linked" as the first HIV-related service accessed
      following HIV diagnosis and "retained" as having, within a calendar year, either:
      (i) at least two HIV-related physician visits/diagnostic tests or (ii) at least
      two antiretroviral therapy (ART) dispensations, >= 3 months apart. Individuals
      were followed until they were retained, died, their last contact date, or until
      31 December 2011, whichever occurred first. RESULTS: Of 5231 linked individuals
      (78% male; median age 39: (Q1-Q3: 32-46) years], 4691 (90%) were retained [median
      time to initial retention of 9 (Q1-Q3: 5-13) months] by the end of follow-up and
      540 (10%) were not. Eighty-four per cent of not retained and 96% of retained
      individuals used at least one type of NHRHS during follow-up. Individuals who saw
      a specialist for NHRHS during follow-up had a shorter time to initial retention
      than those who did not [adjusted hazard ratio (aHR) 2.79; 95% confidence interval
      (CI): 2.47-3.16]. However, those who saw a general practitioner (GP) for NHRHS
      (aHR 0.79; 95% CI: 0.74-0.84) and those admitted to the hospital for NHRHS (aHR
      0.60; 95% CI: 0.54-0.67), versus those who did/were not, respectively, had longer
      times to initial retention, as did female patients, people who inject drugs
      (PWID) and individuals < 40 years old. CONCLUSIONS: Overall, 84% of not retained
      individuals used some type of NHRHS during follow-up. Given that 71% of not
      retained individuals used GP NHRHS, our results suggest that GP-targeted
      interventions may be effective in improving time to initial retention.

PMID- 26216129
TI  - Mesenchymal Stem Cells: Key Actors in Tumor Niche.
AB  - Tumors grow in privileged microenvironment referred to as the cancer niche. This
      niche is composed of cancer cells and various components including mesenchymal
      stem cells (MSC), fibroblasts, network of microvasculature added to innate and
      primed immune cells. Additionally, it encloses other elements such as the
      extracellular matrix (ECM), cytokines, chemokines and growth factors. Crosstalk
      between cancer cells and different niche constituents is crucial for tumor growth
      and metastasis. Herein, we focus attention on the bidirectional relationship
      between MSC and cancer cells and its impact on tumor progression. Better
      comprehension of these events within the tumor niche might be valuable for
      developing effective anti-tumor therapeutic strategies. 

PMID- 26216130
TI  - The Therapeutic Potential of Induced Pluripotent Stem Cells After Stroke:
      Evidence from Rodent Models.
AB  - Stroke is the second most common cause of death and the leading cause of
      disability in the world. About 30% of the people that are affected by stroke die
      within a year; 25% of the patients that survive stroke remain in need of care
      after a year. Therefore, stroke is a major burden for health care costs. The most
      common subtype is ischemic stroke. This type is characterized by a reduced and
      insufficient blood supply to a certain part of the brain. Despite the high
      prevalence of stroke, the currently used therapeutic interventions are limited.
      No therapies that aim to restore damaged neuronal tissue or to promote recovery
      are available nowadays. Transplantation of stem cell-derived cells has been
      investigated as a potential regenerative and protective treatment. Embryonic stem
      cell (ESC)-based cell therapy in rodent models of stroke has been shown to
      improve functional outcome. However, the clinical use of ESCs still raises
      ethical questions and implantation of ESC-derived cells requires continuous
      immunosuppression. The groundbreaking detection of induced pluripotent stem cells
      (iPSCs) has provided a most promising alternative. This mini-review summarizes
      current literature in which the potential use of iPSC-derived cells has been
      tested in rodent models of stroke. iPSC-based cell therapy has been demonstrated
      to improve motor function, decrease stroke volume, promote neurogenesis and
      angiogenesis and to exert immunomodulatory, anti-inflammatory effects in the
      brain of stroke-affected rodents. 

PMID- 26216131
TI  - Expression and Function of PPARs in Cancer Stem Cells.
AB  - Cancer stem cells (CSCs) are cancer cells with characteristics of stem cells,
      especially the ability to arise to all types of cell in a particular cancer
      tissue. With the capacity to generate multiple types of cancer cells, CSCs are
      proposed as primary impetus for tumor initiation and metastases and are suggested
      as potential therapeutic targets for anti-cancer treatment. Peroxisome
      proliferator-activated receptors (PPARs) are a subset of multifunctional
      transcription factors which play a pivotal role in cancer development and
      tumorigenesis. PPARs are also reported to be involved in the modulation of the
      epithelial-mesenchymal transition (EMT) process in CSC initiation and in the
      regulation of CSC functions. However, the exact mechanisms remain unknown.
      Herein, we review the latest evidence on the regulatory effects and mechanisms of
      PPARs in CSC formation and function, and evaluate the prospects of PPARs as a
      target for cancer treatment.

PMID- 26216132
TI  - Histochemical Insights into Pancreatic Islet Biology.

PMID- 26216133
TI  - A Historical Perspective on the Identification of Cell Types in Pancreatic Islets
      of Langerhans by Staining and Histochemical Techniques.
AB  - Before the middle of the previous century, cell types of the pancreatic islets of
      Langerhans were identified primarily on the basis of their color reactions with
      histological dyes. At that time, the chemical basis for the staining properties
      of islet cells in relation to the identity, chemistry and structure of their
      hormones was not fully understood. Nevertheless, the definitive islet cell types
      that secrete glucagon, insulin, and somatostatin (A, B, and D cells,
      respectively) could reliably be differentiated from each other with staining
      protocols that involved variations of one or more tinctorial techniques, such as
      the Mallory-Heidenhain azan trichrome, chromium hematoxylin and phloxine,
      aldehyde fuchsin, and silver impregnation methods, which were popularly used
      until supplanted by immunohistochemical techniques. Before antibody-based
      staining methods, the most bona fide histochemical techniques for the
      identification of islet B cells were based on the detection of sulfhydryl and
      disulfide groups of insulin. The application of the classical islet tinctorial
      staining methods for pathophysiological studies and physiological experiments was
      fundamental to our understanding of islet architecture and the physiological
      roles of A and B cells in glucose regulation and diabetes. 

PMID- 26216134
TI  - Progenitor Epithelium: Sorting Out Pancreatic Lineages.
AB  - Insulin-producing beta cells within the vertebrate fetal pancreas acquire their
      fate in a step-wise manner. Whereas the intrinsic factors dictating the
      transcriptional or epigenetic status of pancreatic lineages have been intensely
      examined, less is known about cell-cell interactions that might constitute a
      niche for the developing beta cell lineage. It is becoming increasingly clear
      that understanding and recapitulating these steps may instruct in vitro
      differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed,
      directed differentiation techniques have improved since transitioning from 2D to
      3D cultures, suggesting that the 3D microenvironment in which beta cells are born
      is critical. However, to date, it remains unknown whether the changing
      architecture of the pancreatic epithelium impacts the fate of cells therein. An
      emerging challenge in the field is to elucidate how progenitors are allocated
      during key events, such as the stratification and subsequent resolution of the
      pre-pancreatic epithelium, as well as the formation of lumens and branches. Here,
      we assess the progenitor epithelium and examine how it might influence the
      emergence of pancreatic multipotent progenitors (MPCs), which give rise to beta
      cells and other pancreatic lineages. 

PMID- 26216135
TI  - Alpha-, Delta- and PP-cells: Are They the Architectural Cornerstones of Islet
      Structure and Co-ordination?
AB  - Islet non-beta-cells, the alpha- delta- and pancreatic polypeptide cells (PP
      cells), are important components of islet architecture and intercellular
      communication. In alpha-cells, glucagon is found in electron-dense granules;
      granule exocytosis is calcium-dependent via P/Q-type Ca(2+)-channels, which may
      be clustered at designated cell membrane sites. Somatostatin-containing delta
      cells are neuron-like, creating a network for intra-islet communication.
      Somatostatin 1-28 and 1-14 have a short bioactive half-life, suggesting
      inhibitory action via paracrine signaling. PP-cells are the most infrequent islet
      cell type. The embryologically separate ventral pancreas anlage contains PP-rich
      islets that are morphologically diffuse and alpha-cell deficient. Tissue samples
      taken from the head region are unlikely to be representative of the whole
      pancreas. PP has anorexic effects on gastro-intestinal function and alters
      insulin and glucagon secretion. Islet architecture is disrupted in rodent
      diabetic models, diabetic primates and human Type 1 and Type 2 diabetes, with an
      increased alpha-cell population and relocation of non-beta-cells to central areas
      of the islet. In diabetes, the transdifferentiation of non-beta-cells, with
      changes in hormone content, suggests plasticity of islet cells but cellular
      function may be compromised. Understanding how diabetes-related disordered islet
      structure influences intra-islet cellular communication could clarify how non
      beta-cells contribute to the control of islet function.

PMID- 26216136
TI  - Hyaluronan: A Mediator of Islet Dysfunction and Destruction in Diabetes?
AB  - Hyaluronan (HA) is an extracellular matrix (ECM) component that is present in
      mouse and human islet ECM. HA is localized in peri-islet and intra-islet regions
      adjacent to microvessels. HA normally exists in a high molecular weight form,
      which is anti-inflammatory. However, under inflammatory conditions, HA is
      degraded into fragments that are proinflammatory. HA accumulates in islets of
      human subjects with recent onset type 1 diabetes (T1D), and is associated with
      myeloid and lymphocytic islet infiltration, suggesting a possible role for HA in
      insulitis. A similar accumulation of HA, in amount and location, occurs in non
      obese diabetic (NOD) and DORmO mouse models of T1D. Furthermore, HA accumulates
      in follicular germinal centers and in T-cell areas in lymph nodes and spleen in
      both human and mouse models of T1D, as compared with control tissues. Whether HA
      accumulates in islets in type 2 diabetes (T2D) or models thereof has not been
      previously described. Here we show evidence that HA accumulates in a mouse model
      of islet amyloid deposition, a well-known component of islet pathology in T2D. In
      summary, islet HA accumulation is a feature of both T1D and a model of T2D, and
      may represent a novel inflammatory mediator of islet pathology.

PMID- 26216137
TI  - MMTV/LTR Promoter-Driven Transgenic Expression of EpCAM Leads to the Development
      of Large Pancreatic Islets.
AB  - Our previous work demonstrated an important role of EpCAM in the regulation of
      pancreatic cell adhesion, growth and differentiation. Here we investigated the
      consequences of human EpCAM (hEpCAM) overexpression under the control of the MMTV
      LTR promoter, known to drive robust gene expression in a number of ductal
      epithelia, including the pancreas. In this animal model (MMTV-hEpCAM) we
      uncovered a striking pancreatic phenotype exhibiting a 12-fold increase in the
      islet cell mass, with normal expression patterns of insulin and the transcription
      factor PDX-1. Intriguingly, these large islet clusters revealed an altered
      architectural organization of alpha- and delta-cells that appeared interspersed
      with beta-cells in the islet cores. This suggests an effect of the hEpCAM
      transgene on the function of other cell adhesion molecules that we have
      previously shown to regulate islet cell type segregation. Consistent with this
      finding, we show that the pancreatic epithelium in MMTV-hEpCAM transgenic mice
      exhibits a redistribution of beta-catenin, a known regulator of E-cadherin
      mediated adhesions. Collectively, these results provide an important in vivo
      validation of hEpCAM signaling properties in normal epithelia and offer unique
      opportunities to further explore the function of this glycoprotein in select
      pancreatic cell lineages to elicit islet cell expansion, and/or regeneration in
      diabetes.

PMID- 26216138
TI  - Heterogeneity and Lobularity of Pancreatic Pathology in Type 1 Diabetes during
      the Prediabetic Phase.
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta
      cells are destroyed in the islets of Langerhans. One of its main pathological
      manifestations is the hyper-expression of Major Histocompatibility Complex I (MHC
      I) by beta cells, which was first described over 3 decades ago yet its cause
      remains unknown. It might not only be a sign of beta cell dysfunction but could
      also render the cells susceptible to autoimmune destruction; for example, by
      islet-infiltrating CD8 T cells. In this report, we studied pancreas tissue from a
      22-year-old non-diabetic male cadaveric organ donor who had been at high risk of
      developing T1D, in which autoantibodies against GAD and IA-2 were detected.
      Pancreas sections were analyzed for signs of inflammation. Multiple insulin
      containing islets were identified, which hyper-expressed MHC-I. However, islet
      density and MHC-I expression exhibited a highly lobular and heterogeneous pattern
      even within the same section. In addition, many islets with high expression of
      MHC-I presented higher levels of CD8 T cell infiltration than normal islets.
      These results demonstrate the heterogeneity of human pathology that occurs early
      during the pre-diabetic, autoantibody positive phase, and should contribute to
      the understanding of human T1D.

PMID- 26216140
TI  - Characterization of Antibodies to Products of Proinsulin Processing Using
      Immunofluorescence Staining of Pancreas in Multiple Species.
AB  - The efficient processing of proinsulin into mature insulin and C-peptide is often
      compromised under conditions of beta cell stress, including diabetes. Impaired
      proinsulin processing has been challenging to examine by immunofluorescence
      staining in pancreas tissue because the characterization of antibodies specific
      for proinsulin, proinsulin intermediates, processed insulin and C-peptide has
      been limited. This study aimed to identify and characterize antibodies that can
      be used to detect products of proinsulin processing by immunofluorescence
      staining in pancreata from different species (mice, rats, dog, pig and human). We
      took advantage of several knockout mouse lines that lack either an enzyme
      involved in proinsulin processing or an insulin gene. Briefly, we report
      antibodies that are specific for several proinsulin processing products,
      including: a) insulin or proinsulin that has been appropriately processed at the
      B-C junction; b) proinsulin with a non-processed B-C junction; c) proinsulin with
      a non-processed A-C junction; d) rodent-specific C-peptide 1; e) rodent-specific
      C-peptide 2; and f) human-specific C-peptide or proinsulin. In addition, we also
      describe two 'pan-insulin' antibodies that react with all forms of insulin and
      proinsulin intermediates, regardless of the species. These antibodies are
      valuable tools for studying proinsulin processing by immunofluorescence staining
      and distinguishing between proinsulin products in different species.

PMID- 26216139
TI  - Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet
      Vascular Structures Is Increased in Type 2 Diabetes.
AB  - Human and rodent islets differ substantially in several features, including
      architecture, cell composition, gene expression and some aspects of insulin
      secretion. Mouse pancreatic islets are highly vascularized with interactions
      between islet endothelial and endocrine cells being important for islet cell
      differentiation and function. To determine whether human islets have a similar
      high degree of vascularization and whether this is altered with diabetes, we
      examined the vascularization of islets from normal human subjects, subjects with
      type 2 diabetes (T2D), and normal mice. Using an integrated morphometry approach
      to quantify intra-islet capillary density in human and mouse pancreatic sections,
      we found that human islets have five-fold fewer vessels per islet area than mouse
      islets. Islets in pancreatic sections from T2D subjects showed capillary
      thickening, some capillary fragmentation and had increased vessel density as
      compared with non-diabetic controls. These changes in islet vasculature in T2D
      islets appeared to be associated with amyloid deposition, which was noted in
      islets from 8/9 T2D subjects (and occupied 14% +/- 4% of islet area), especially
      around the intra-islet capillaries. The physiological implications of the
      differences in the angioarchitecture of mouse and human islets are not known.
      Islet vascular changes in T2D may exacerbate beta cell/islet dysfunction and beta
      cell loss.

PMID- 26216141
TI  - Determination of Optimal Sample Size for Quantification of beta-Cell Area,
      Amyloid Area and beta-Cell Apoptosis in Isolated Islets.
AB  - Culture of isolated rodent islets is widely used in diabetes research to assess
      different endpoints, including outcomes requiring histochemical staining. As
      islet yields during isolation are limited, we determined the number of islets
      required to obtain reliable data by histology. We found that mean values for
      insulin-positive beta-cell area/islet area, thioflavin S-positive amyloid
      area/islet area and beta-cell apoptosis do not vary markedly when more than 30
      islets are examined. Measurement variability declines as more islets are
      quantified, so that the variability of the coefficient of variation (CV) in human
      islet amyloid polypeptide (hIAPP) transgenic islets for beta-cell area/islet
      area, amyloid area/islet area and beta-cell apoptosis are 13.20% +/- 1.52%,
      10.03% +/- 1.76% and 6.78% +/- 1.53%, respectively (non-transgenic: 7.65% +/-
      1.17% beta-cell area/islet area and 8.93% +/- 1.56% beta-cell apoptosis).
      Increasing the number of islets beyond 30 had marginal effects on the CV. Using
      30 islets, 6 hIAPP-transgenic preparations are required to detect treatment
      effects of 14% for beta-cell area/islet area, 30% for amyloid area/islet area and
      23% for beta-cell apoptosis (non-transgenic: 9% for beta-cell area/islet area and
      45% for beta-cell apoptosis). This information will be of value in the design of
      studies using isolated islets to examine beta cells and islet amyloid.

PMID- 26216142
TI  - Studying common-pool resources over time: A longitudinal case study of the Buen
      Hombre fishery in the Dominican Republic.
AB  - Like many small-scale fishing communities around the world, the community of Buen
      Hombre in the Dominican Republic is dealing with a set of challenges to reconcile
      its fishing activities with the ecology on which it depends. Also like many such
      communities, this case has been examined at a particular period in time by a
      group of social scientists, but not over substantial lengths of time in order to
      examine the longitudinal validity of the conclusions made during this period. In
      this paper we combine data from previous anthropological work with our own
      primary social and ecological data to conduct a longitudinal case study of the
      Buen Hombre fishery. Our over-time comparison focuses on a suite of mostly social
      and institutional variables to explain what we find to be a continued degradation
      of the fishery, and we conclude the analysis by presenting a causal-loop diagram,
      summarizing our inferences regarding the complex interactions among these
      variables. We find that a mix of factors, notably changes in gear and fishing
      sites used, the number of fishermen and their livelihood diversity, as well as an
      increased connectivity between Buen Hombre and its external environment, have
      contributed to the decline of the condition of Buen Hombre coral reef fishery. We
      conclude with a discussion of what may lie ahead for this particular case and
      others like it. 

PMID- 26216143
TI  - Human-mediated dispersal of aquatic invertebrates with waterproof footwear.
AB  - Human-mediated dispersal has rarely been considered in wetland conservation
      strategies at regional scales, yet high concern exists about this aspect for
      (inter-)national management considering invasive species in other aquatic
      systems. In this context, we aim at understanding the role of human-mediated
      dispersal by footwear in protected wetlands with high conservation value.
      Zooplankton and zoobenthos were sampled in 13 shallow lakes in central Spain and,
      at the same time, mud attached to waders was collected and later cultured in
      deionized water under laboratory conditions for 4 weeks. Two-hundred and four
      individuals belonging to 19 invertebrate taxa were recovered after hatching;
      Ostracoda (84 %), Cladocera (53 %), Copepoda (30 %), Anostraca (30 %), and
      Notostraca (7 %) were the most frequent groups among the hatched crustaceans.
      NMDS and PERMANOVA analyses showed significant differences between the dispersed
      (via footwear) and the source active metacommunity, suggesting different
      dispersal abilities among the species found. Human vectors facilitate dispersal
      among protected lakes, which could eventuality lead to biotic homogenization and
      faster spread of non-indigenous species. Preservation strategies and education
      campaigns associated to target humans in close contact with water bodies should
      be imperative in conservation management of protected lakes.

PMID- 26216144
TI  - A galloping quadruped model using left-right asymmetry in touchdown angles.
AB  - Among quadrupedal gaits, the galloping gait has specific characteristics in terms
      of locomotor behavior. In particular, it shows a left-right asymmetry in gait
      parameters such as touchdown angle and the relative phase of limb movements. In
      addition, asymmetric gait parameters show a characteristic dependence on
      locomotion speed. There are two types of galloping gaits in quadruped animals:
      the transverse gallop, often observed in horses; and the rotary gallop, often
      observed in dogs and cheetahs. These two gaits have different footfall sequences.
      Although these specific characteristics in quadrupedal galloping gaits have been
      observed and described in detail, the underlying mechanisms remain unclear. In
      this paper, we use a simple physical model with a rigid body and four massless
      springs and incorporate the left-right asymmetry of touchdown angles. Our
      simulation results show that our model produces stable galloping gaits for
      certain combinations of model parameters and explains these specific
      characteristics observed in the quadrupedal galloping gait. The results are then
      evaluated in comparison with the measured data of quadruped animals and the gait
      mechanisms are clarified from the viewpoint of dynamics, such as the roles of the
      left-right touchdown angle difference in the generation of galloping gaits and
      energy transfer during one gait cycle to produce two different galloping gaits. 

PMID- 26216145
TI  - Purification and Characterization of a Lipase with High Thermostability and Polar
      Organic Solvent-Tolerance from Aspergillus niger AN0512.
AB  - An extracellular lipase (EC 3.1.1.3, AN0512Lip) from Aspergillus niger AN0512 was
      purified and its characteristics were investigated. After the process of ammonium
      sulfate precipitation followed by ion-exchange chromatography and gel filtration,
      the purified lipase was achieved with 203.6-fold purification and 22.1 %
      recovery. AN0512Lip exhibited the highest activity at 50  degrees C and pH 5.0.
      It was thermostable and pH-stable, as indicated by that more than 50 % activity
      retained at 60  degrees C for 20 h and more than 90 % activity retained at pH 3.0
      for 20 h, respectively. AN0512Lip activity was stimulated by some divalent metal
      ions (especially Cu(2+), Ca(2+)), while greatly suppressed by EDTA, indicating
      that AN0512Lip was a metal-activated enzyme. Moreover, AN0512Lip exhibited high
      tolerance for various polar organic solvents with log P < 0.8, and the highest
      lipase activity (476 % of its original activity) was achieved after addition of
      90 % (V/V) isopropanol to the reaction mixture. AN0512Lip also displayed 3
      regiospecificity and great affinity for the long-chain fatty ester. The
      preliminary test showed that AN0512Lip was a candidate for enriching EPA and DHA
      in fish oil. All the unique properties, such as thermostability, Cu(2+)
      dependent, 3-regiospecificity, and polar organic solvent-tolerance, indicated
      that AN0512Lip could have potential applications in the food industry, even in
      organic synthesis and the pharmaceutical industry.

PMID- 26216147
TI  - Introduction to the special section on sexual health in gay and bisexual men.

PMID- 26216146
TI  - Substance use homophily among geosocial networking application using gay,
      bisexual, and other men who have sex with men.
AB  - Geosocial networking applications (GSN apps) represent important virtual contexts
      in which gay, bisexual, and other men who have sex with men (MSM) seek
      affiliation. These apps allow users to create and view public profiles, send
      photos, and text messages, and connect with other users based on shared interests
      and geographic proximity. The present study examined substance use homophily
      among a sample of 295 MSM recruited via a popular GSN app. Comparisons of social
      network members met via GSN app versus elsewhere and associations between both
      individual and network characteristics and recent binge drinking, marijuana use,
      and illicit substance use were explored using bivariate tests of association and
      multivariate logistic regression analyses. High rates of recent binge drinking
      (59 %), marijuana use (37 %), and illicit substance use (27 %) were observed
      among participants. GSN app use greater than 1 year and showing naked chest or
      abs in a profile picture were positively associated with recent illicit substance
      use. In multivariate analyses, the strongest predictors of binge drinking (AOR
      3.81; 95 % CI 1.86-7.80), marijuana use (AOR 4.12; 95 % CI 2.22-7.64), and
      illicit substance use (AOR 6.45; 95 % CI 3.26-12.79) were the presence of a
      social network member who also engaged in these behaviors. Social network
      interventions that target binge drinking, marijuana use, and illicit substance
      use may be delivered via GSN apps to reduce the prevalence of substance use and
      related risks among MSM in these virtual contexts. 

PMID- 26216148
TI  - Human sexual behavior and the origins of gonorrhea.

PMID- 26216149
TI  - Correction.

PMID- 26216150
TI  - Euthanasia requests, procedures and outcomes for 100 Belgian patients suffering
      from psychiatric disorders: a retrospective, descriptive study.
AB  - OBJECTIVES: To identify patterns in euthanasia requests and practices relating to
      psychiatric patients; to generate recommendations for future research. DESIGN:
      Retrospective analysis of data obtained through medical file review. SETTING:
      Outpatient psychiatric clinical setting in the Dutch-speaking region of Belgium,
      between October 2007 and December 2011; follow-up at the end of December 2012.
      PARTICIPANTS: 100 consecutive psychiatric patients requesting euthanasia based on
      psychological suffering associated with psychiatric disorders (77 women, 23 men;
      mean age 47 years; age range 21-80 years). MAIN OUTCOME MEASURES: Patient
      sociodemographic characteristics; diagnoses; decisions on euthanasia requests;
      circumstances of euthanasia procedures; patient outcomes at follow-up. RESULTS:
      Most patients had been referred for psychiatric counselling by their physician
      (n=55) or by LEIF (Life End Information Forum) (n=36). 90 patients had >1
      disorder; the most frequent diagnoses were depression (n=58) and personality
      disorder (n=50). 38 patients required further testing and/or treatment, including
      13 specifically tested for autism spectrum disorder (ASD); 12 received an ASD
      diagnosis (all Asperger syndrome). In total, 48 of the euthanasia requests were
      accepted and 35 were carried out. Of the 13 remaining patients whose requests
      were accepted, 8 postponed or cancelled the procedure, because simply having this
      option gave them enough peace of mind to continue living. In December 2012, 43
      patients had died, including 35 by euthanasia; others died by suicide (6),
      palliative sedation (1) and anorexia nervosa (1). CONCLUSIONS: Depression and
      personality disorders are the most common diagnoses in psychiatric patients
      requesting euthanasia, with Asperger syndrome representing a neglected disease
      burden. Further research is needed, especially prospective quantitative and
      qualitative studies, to obtain a better understanding of patients with
      psychiatric disorders who request euthanasia due to unbearable psychological
      suffering.

PMID- 26216151
TI  - Correction.

PMID- 26216153
TI  - Correction.

PMID- 26216152
TI  - Floor and ceiling effects in the OHS: an analysis of the NHS PROMs data set.
AB  - OBJECTIVES: The objective was to examine whether the Oxford Hip Score (OHS)
      demonstrated a floor or a ceiling effect when used to measure the outcome of hip
      replacement surgery in a large national cohort. SETTING: Secondary database
      analysis of a national audit conducted in England and Wales on patient undergoing
      hip and knee arthroplasty in a secondary care setting. PARTICIPANTS: 93 253
      primary arthroplasty patients completed preoperative OHS questionnaires and 69
      361 completed 6-month postoperative OHS questionnaires. The population had a mean
      age of 67.78 (range 14-100, SD 11.3) and 59% were female. PRIMARY SECONDARY
      OUTCOME MEASURES: Primary outcome measure was the Oxford Hip Score (OHS).
      Secondary outcome measures were the OHS-FCS and OHS-PCS. Floor and ceiling
      effects were considered present if >15% of patients achieved the worst
      score/floor effect (0/48) or best/ceiling effect (48/48) score. RESULTS:
      Preoperatively, 0% of patients achieved the best score (48) and 0.1% achieved the
      worst score (0). Postoperatively, 0.1% patients achieved the worst score, but the
      percentage achieving the best score increased to 11.6%. Subgroup analyses
      demonstrated that patients between 50 and 59 years of age had the highest
      postoperative best score, at 15.3%. The highest postoperative OHS worst score
      percentage was in a group of patients who had a preoperative OHS above 41/48 at
      28%. Furthermore, 22.6% of patients achieved the best postoperative OHS-PCS and
      19.9% best postoperative OHS-FCS. CONCLUSIONS: Based on NHS PROMS data the
      overall OHS does not exhibit a ceiling or floor effect and should continue to be
      used as a valid measure of patient-reported outcomes for patients undergoing
      total hip arthroplasty. However, subscale analysis does indicate some limitations
      in the OHS-PCS and OHS-FCS. TRIAL REGISTRATION NUMBER: NDORMS. Introducing
      standardised and evidence-based thresholds for hip and knee replacement surgery.
      The Arthroplasty Candidacy Help Engine (ACHE tool). HTA Project 11/63/01.

PMID- 26216154
TI  - Outcomes of the Northern Ontario School of Medicine's distributed medical
      education programmes: protocol for a longitudinal comparative multicohort study.
AB  - INTRODUCTION: The Northern Ontario School of Medicine (NOSM) has a social
      accountability mandate to serve the healthcare needs of the people of Northern
      Ontario, Canada. A multiyear, multimethod tracking study of medical students and
      postgraduate residents is being conducted by the Centre for Rural and Northern
      Health Research (CRaNHR) in conjunction with NOSM starting in 2005 when NOSM
      first enrolled students. The objective is to understand how NOSM's selection
      criteria and medical education programmes set in rural and northern communities
      affect early career decision-making by physicians with respect to their choice of
      medical discipline, practice location, medical services and procedures, inclusion
      of medically underserved patient populations and practice structure. METHODS AND
      ANALYSIS: This prospective comparative longitudinal study follows multiple
      cohorts from entry into medical education programmes at the undergraduate (UG)
      level (56-64 students per year at NOSM) or postgraduate (PG) level (40-60
      residents per year at NOSM, including UGs from other medical schools and 30-40
      NOSM UGs who go to other schools for their residency training) and continues at
      least 5 years into independent practice. The study compares learners who
      experience NOSM UG and NOSM PG education with those who experience NOSM UG
      education alone or NOSM PG education alone. Within these groups, the study also
      compares learners in family medicine with those in other specialties. Data will
      be analysed using descriptive statistics, chi(2) tests, logistic regression, and
      hierarchical log-linear models. ETHICS AND DISSEMINATION: Ethical approval was
      granted by the Research Ethics Boards of Laurentian University (REB #2010-08-03
      and #2012-01-09) and Lakehead University (REB #031 11-12 Romeo File #1462056).
      Results will be published in peer-reviewed scientific journals, presented at one
      or more scientific conferences, and shared with policymakers and decision-makers
      and the public through 4-page research summaries and social media such as Twitter
      (@CRaNHR, @NOSM) or Facebook.

PMID- 26216155
TI  - Pediatric ureteropelvic junction obstruction: can magnetic resonance urography
      identify crossing vessels?
AB  - BACKGROUND: MR Urography (MRU) is an increasingly used imaging modality for the
      evaluation of pediatric genitourinary obstruction. OBJECTIVE: To determine
      whether pediatric MR urography (MRU) reliably detects crossing vessels in the
      setting of suspected ureteropelvic junction (UPJ) obstruction. The clinical
      significance of these vessels was also evaluated. MATERIALS AND METHODS: We
      identified pediatric patients diagnosed with UPJ obstruction by MRU between May
      2009 and June 2014. MRU studies were evaluated by two pediatric radiologists for
      the presence or absence of crossing vessels. Ancillary imaging findings such as
      laterality, parenchymal thinning/scarring, trapped fluid in the proximal ureter,
      and presence of renal parenchymal edema were also evaluated. Imaging findings
      were compared to surgical findings. We used the Mann-Whitney U test to compare
      continuous data and the Fisher exact test to compare proportions. RESULTS: Twenty
      four of 25 (96%) UPJ obstructions identified by MRU were surgically confirmed.
      MRU identified crossing vessels in 10 of these cases, with 9 cases confirmed
      intraoperatively (kappa = 0.92 [95% CI: 0.75, 1.0]). Crossing vessels were
      determined to be the primary cause of UPJ obstruction in 7/9 children
      intraoperatively, while in two children the vessels were deemed incidental and
      noncontributory to the urinary tract obstruction. There was no significant
      difference in age or the proportions of ancillary findings when comparing
      children without and with obstructing vessels. CONCLUSION: MRU allows detection
      of crossing vessels in pediatric UPJ obstruction. Although these vessels are the
      primary cause of obstruction in some children, they are incidental and non
      contributory in others. Our study failed to convincingly identify any significant
      predictors (e.g., age or presence of renal parenchymal edema) that indicate when
      a crossing vessel is the primary cause of obstruction.

PMID- 26216156
TI  - Findings at brain MRI in children with dengue fever and neurological symptoms.
AB  - Dengue is a flavivirus of the genus arbovirus with four serotypes, from DEN 1 to
      DEN 4. There has been an increase in incidence of dengue infection in children in
      the tropics and subtropics. Dengue has a variable clinical presentation, with
      many patients being asymptomatic. Its clinical manifestations in children vary
      from fever and arthralgia to life-threatening dengue hemorrhagic fever and dengue
      shock syndrome. We describe MRI findings in children with neurological
      involvement including dengue encephalopathy, acute hypoxic injury and dengue
      encephalitis. Dengue encephalopathy is usually secondary to multisystem
      derangement such as shock, hepatitis, coagulopathy and concurrent bacterial
      infection and is relatively common. Dengue encephalitis from direct neuronal
      invasion is rare. Nonspecific changes are seen on brain MRI in dengue infection.
      Clinical and laboratory findings as well as outcome do not necessarily correspond
      with brain MRI findings. 

PMID- 26216158
TI  - Study of Toxocara seroprevalence among patients with allergy and healthy
      individuals in Bulgaria.
AB  - Data in the literature addressing the ability of Toxocara infection in humans to
      induce development of atopic disease are controversial. The aim of our study was
      to determine the seroprevalence of anti-Toxocara antibodies in three groups of
      people: subjects with allergic symptoms and presence of allergen-specific IgE,
      subjects with allergic symptoms and absence of allergen-specific IgE, and
      clinically healthy blood donors. Serum samples from all subjects were tested by
      ELISA and Western blot for presence of specific antibodies against Toxocara
      canis. The results of our study did not support the link between toxocariasis and
      allergic manifestations in atopic patients. Among subjects with allergic symptoms
      and absence of atopy was found seroprevalence of 2.2% in Western blot. Same index
      in patients with atopy was 0.8%, and in clinically healthy blood donors 4.0%. Our
      study gives us grounds to consider that it is appropriate persons with allergic
      reactions, without evidence of atopy to be tested for presence of anti-Toxocara
      antibodies in the course of their diagnostic evaluation. Data from clinically
      healthy persons suggest that there is a 'hidden' infection among the population,
      which is not clinically manifested.

PMID- 26216157
TI  - Pediatric elbow fractures: a new angle on an old topic.
AB  - BACKGROUND: The three most common elbow fractures classically reported in
      pediatric orthopedic literature are supracondylar (50-70%), lateral condylar (17
      34%), and medial epicondylar fractures (10%), with fractures of the proximal
      radius (including but not limited to fractures of the radial neck) being
      relatively uncommon (5-10%). Our experience at a large children's hospital
      suggests a different distribution. OBJECTIVE: Our goals were (1) to ascertain the
      frequency of different elbow fracture types in a large pediatric population, and
      (2) to determine which fracture types were occult on initial radiographs but
      detected on follow-up. MATERIALS AND METHODS: Review of medical records
      identified 462 children, median age 6 years and interquartile range for age of 4
      8 years (range 0.8-18 years), who were diagnosed with elbow fractures at our
      institution over a 10-month period. Initial and follow-up radiographs were
      reviewed in blinded fashion independently by two experienced pediatric
      musculoskeletal radiologists to identify fracture types on initial and follow-up
      radiographs. RESULTS: The most common fractures included supracondylar (n = 258,
      56%), radial neck (n = 80, 17%), and lateral condylar (n = 69, 15%). Additional
      fractures were seen on follow-up exams in 32 children. Of these, 25 had a
      different fracture type than was identified on initial radiographs. The most
      common follow-up fractures were olecranon (n = 23, 72%), coronoid process (n = 4,
      13%) and supracondylar (n = 3, 9%). Olecranon fractures were significantly more
      common on follow-up radiographs than they were on initial radiographs (n = 33,
      7%; P < .0001). Twenty-six children had more than one fracture type on the
      initial radiograph. The most common fracture combinations were radial neck with
      olecranon (n = 9) and supracondylar with lateral condylar (n = 9). CONCLUSION:
      Supracondylar fractures are the most frequent elbow fracture seen initially,
      followed by radial neck, lateral condylar, and olecranon fractures in a
      distribution different from what has been historically described. The relatively
      high frequency of olecranon fractures detected on follow-up speaks to their
      potentially occult nature. Careful attention to these areas is warranted in
      children with initially normal radiographs.

PMID- 26216159
TI  - Trainers' and trainees' perceptions of workplace-based assessment in
      orthodontics.
AB  - AIMS: To explore trainers' and trainees' perceptions and experiences of Workplace
      Based Assessments (WBAs) in Orthodontic Speciality Registrar (StR) training in
      England. DESIGN: Cross-sectional questionnaire survey. SETTING: UK. PARTICIPANTS:
      Orthodontic StRs who had started their training in 2011-2012 and their trainers.
      METHODS: Participants completed an anonymous on-line questionnaire in July-August
      2013.Statistical analysis included descriptive statistics and frequency
      distributions. RESULTS: The questionnaire was completed by 42% (76/180) of
      trainers and 62% (46/74) of trainees. Half of the trainers spent 0.25 programmed
      activity (PA) per month undertaking WBAs. However, 88% of trainers had no PAs in
      their job plan for WBAs. The majority (53/66, 80%) of trainers undertook up to
      half of the WBAs in their SPAs. The trainers undertook a median of 5.5
      (Interquartile range = 4) WBAs per trainee per year. Trainees spent an average of
      an hour per month undertaking WBAs. The mean number of completed WBAs per year
      was 12 (SD 4.2; 95%CI 10.7, 13.7) and mode was 10 WBAs. Almost all trainees,
      (33/34) had more than 80% of their WBAs undertaken by Consultants. CONCLUSIONS:
      There was no statistically significant difference in trainers' and trainees'
      perception of the WBAs, and were accepted by both the trainers and trainees.
      Trainers and trainees spent about 1 hour per month undertaking WBAs. The majority
      of trainers undertook the WBAs in their SPA time. Trainees appeared to be
      undertaking the recommended number of WBAs.

PMID- 26216160
TI  - Estradiol-induced alopecia in five dogs after contact with a transdermal gel used
      for the treatment of postmenopausal symptoms in women.
AB  - BACKGROUND: Noninflammatory alopecia is a frequent problem in dogs. Estrogen
      induced alopecia is well described in dogs, with estrogen producing testicular
      tumors and canine female hyperestrogenism. OBJECTIVES: To increase awareness that
      extensive alopecia in dogs can be caused by exposure to estradiol gel used by
      owners to treat their postmenopausal symptoms. ANIMALS: Skin biopsies from five
      dogs with extensive alopecia were examined. METHODS: Owners were asked for a
      thorough case history, including possible exposure to an estradiol gel. Complete
      blood work and serum chemistry panel analysis were performed to investigate
      possible underlying causes. Formalin-fixed skin biopsy samples were obtained from
      lesional skin and histopathology was performed. RESULTS: All owners confirmed the
      use of a transdermal estradiol gel and close contact with the affected dogs
      before development of alopecia. Histopathologic examination showed a similar
      picture in all five dogs. Most hair follicles were predominantly either in
      kenogen or telogen and hair follicle infundibula showed mild to moderate
      dilation. Hair regrowth was present in all five dogs after the exposure to the
      estradiol gel was stopped or minimized. Blood work and serum chemistry panel were
      within normal limits in all cases. One dog had elevated estradiol concentrations,
      whereas in another dog estradiol concentrations were within normal limits.
      CONCLUSION AND CLINICAL IMPORTANCE: Alopecia can occur after contact with a
      transdermal gel used as treatment for postmenopausal symptoms in women. Estradiol
      gel used by female owners therefore represents a possible cause for
      noninflammatory alopecia in dogs. Estradiol concentrations are not necessarily
      elevated in affected dogs.

PMID- 26216161
TI  - Treatment of massive subretinal hematoma associated with age-related macular
      degeneration using vitrectomy with intentional giant tear.
AB  - The purpose of this study was to report the surgical outcomes after creating a
      120 degrees  intentional giant retinal tear for use in removing hemorrhage and
      subretinal proliferative tissue in patients with polypoidal choroidal
      vasculopathy (PCV) or age-related macular degeneration (ARMD). This study
      involved 12 eyes of 12 patients (10 eyes: PCV, 2 eyes: ARMD). After removal of
      the lens in phakic eyes, we performed a vitrectomy with artificial posterior
      vitreous detachment. Subsequently, a 120 degrees  intentional giant retinal tear
      was created in the temporal periphery, the retina was then turned, and the
      subretinal hemorrhage and proliferative tissue were removed. In order to preserve
      as much of the retinal pigment epithelium (RPE) as possible, we used a bimanual
      technique under direct visualization. After stretching the retina by use of
      perfluorocarbon liquid (PFCL), we performed endophotocoagulation around the tear
      followed by PFCL/silicone oil exchange. Except for 1 eye in which extensive loss
      of the RPE occurred, the fundus findings and the visual acuity (VA) improved in
      all patients. In addition, postoperative VA improved to >=20/50 in 3 eyes in
      which the macular RPE was preserved. This surgical procedure is an effective
      treatment for PCV or ARMD patients with extensive subretinal hemorrhage and
      proliferative tissue. 

PMID- 26216162
TI  - Choroidal thickness in relation to demographic and ocular factors in Turkish
      subjects.

PMID- 26216164
TI  - Child-focused treatment of pediatric OCD affects parental behavior and family
      environment.
AB  - This study aimed to investigate the impact of child-focused pediatric OCD
      treatment on parental anxiety, family accommodation and family environment. Forty
      three parents (72.1% female, mean age+/-SD=43.1+/-5.6 years) were evaluated at
      baseline and after their children's (n=33, 54.5% female, mean age+/-SD=12.9+/-2.7
      years) randomized treatment with Group Cognitive-Behavioral Therapy or fluoxetine
      for 14 weeks. Validated instruments were administered by trained clinicians.
      Parents were assessed with the State-Trait Anxiety Inventory (STAI), the Family
      Accommodation Scale (FAS) and the Family Environment Scale (FES). The Yale-Brown
      Obsessive-Compulsive Scale was administered to children. Significant findings
      after the children's treatment include decreased family accommodation levels
      (participation, modification and distress/consequences domains); increased
      cohesion and active-recreational components of the family environment. In
      addition, changes in the FAS distress/consequences and the FES cohesion subscores
      were correlated with the children's clinical improvement. These results suggest
      that child-focused OCD treatment may have a positive impact on family
      accommodation and family environment. Future studies should further clarify the
      reciprocal influences of pediatric OCD treatment and family factors. 

PMID- 26216163
TI  - Identification of somatic gene mutations in penile squamous cell carcinoma.
AB  - There is a lack of studies on somatic gene mutations and cell signaling driving
      penile carcinogenesis. Our objective was to analyze somatic mutations in genes
      downstream of EGFR in penile squamous cell carcinomas, especially the mTOR and
      RAS/MAPK pathways. We retrospectively analyzed somatic mutations in 10 in situ
      and 65 invasive penile squamous cell carcinomas by using Sequenom's Mass
      Spectrometry iPlex Technology and Oncocarta v1.0 Panel. The DNA was extracted
      from FFPE blocks and we identified somatic missense mutations in three in situ
      tumors and in 19 invasive tumors, mostly in PIK3CA, KRAS, HRAS, NRAS, and PDGFA
      genes. Somatic mutations in the PIK3CA gene or RAS family genes were neither
      associated with tumor grade, stage or outcome, and were equally often identified
      in hrHPV positive and in hrHPV negative tumors that showed no p53 expression.
      Mutations in PIK3CA, KRAS, and HRAS are frequent in penile squamous cell
      carcinoma and likely play a role in the development of p53-negative tumors.
      Although the presence of these mutations does not seem to correlate with tumoral
      behavior or outcome, they could be biomarkers of treatment failure with anti-EGFR
      mAb in patients with penile squamous cell carcinoma.

PMID- 26216165
TI  - An exploratory association study of the influence of noradrenergic genes and
      childhood trauma in Borderline Personality Disorder.
AB  - This study investigated the possible association of 40 polymorphisms within 4
      noradrenergic genes with BPD risk and the modulating effect of childhood trauma
      on these associations in 481 BPD subjects and 442 controls. COMT rs5993882, DBH
      rs77905 and SLC6A2 rs1814270 showed associations with BPD, which were modulated
      by childhood trauma. However, none of these findings survived Bonferroni
      correction. Further investigation is needed to clarify the involvement of these
      genes in BPD pathogenesis. 

PMID- 26216166
TI  - A possible contributory mechanism for impaired idiom perception in schizophrenia.
AB  - In this review, we focus on the ability of people with schizophrenia to correctly
      perceive the meaning of idioms; figurative language expressions in which intended
      meaning is not derived from the meaning of constituent words. We collate evidence
      on how idiom perception is impaired, ascertain the clinical relevance of this
      impairment, and consider possible psychological and neural mechanisms behind the
      impairment. In reviewing extant literature, we searched the PubMed database, from
      1975-2014, focussing on articles that directly concerned schizophrenia and
      idioms, with follow up searches to explore the viability of possible underlying
      mechanisms. We learn that there is clear evidence of impairment, with a tendency
      to err towards literal interpretations unless the figurative meaning is salient,
      and despite contextual cues to figurative interpretations. Given the importance
      of idioms in everyday language, the potential impact is significant. Clinically,
      impaired idiom perception primarily relates to positive symptoms of
      schizophrenia, but also to negative symptoms. The origins of the impairment
      remain speculation, with impaired executive function, impaired semantic
      functions, and impaired context processing all proposed to explain the
      phenomenon. We conclude that a possible contributory mechanism at the neural
      level is an impaired dorsolateral prefrontal cortex system for cognitive control
      over semantic processing. 

PMID- 26216167
TI  - Provocative work experiences predict the acquired capability for suicide in
      physicians.
AB  - The interpersonal psychological theory of suicidal behavior (IPTS) offers a
      potential means to explain suicide in physicians. The IPTS posits three necessary
      and sufficient precursors to death by suicide: thwarted belongingness, perceived
      burdensomeness, and acquired capability. The present study sought to examine
      whether provocative work experiences unique to physicians (e.g., placing sutures,
      withdrawing life support) would predict levels of acquired capability, while
      controlling for gender and painful and provocative experiences outside the work
      environment. Data were obtained from 376 of 7723 recruited physicians. Study
      measures included the Acquired Capability for Suicide Scale, the Interpersonal
      Needs Questionnaire, the Painful and Provocative Events Scale, and the Life
      Events Scale-Medical Doctors Version. Painful and provocative events outside of
      work predicted acquired capability (beta=0.23, t=3.82, p<0.001, f(2)=0.09) as did
      provocative work experiences (beta=0.12, t=2.05, p<0.05, f(2)=0.07). This
      represents the first study assessing the potential impact of unique work
      experiences on suicidality in physicians. Limitations include over-representation
      of Caucasian participants, limited representation from various specialties of
      medicine, and lack of information regarding individual differences. 

PMID- 26216168
TI  - Theory-of-mind use in remitted schizophrenia patients: The role of inhibition and
      perspective-switching.
AB  - In social interaction, Theory of Mind (ToM) enables us to construct
      representations of others' mental states, and to use those representations
      flexibly to explain or predict others' behavior. Although previous literature has
      documented that schizophrenia is associated with poor ToM ability, little is
      known about the cognitive mechanisms underlying their difficulty in ToM use. This
      study developed a new methodology to test whether the difficulty in false-belief
      use might be related to deficits in perspective-switching or impaired inhibitory
      control among 23 remitted schizophrenia patients and 18 normal controls. Patients
      showed a significantly greater error rate in a perspective-switching condition
      than a perspective-repeating position in a false-belief-use task, whereas normal
      controls did not show a difference between the two conditions. In addition, a
      larger main effect of inhibition was found in remitted schizophrenia patients
      than normal controls in both a false-belief-use task and control task. Thus,
      remitted schizophrenia patients' impairment in ToM use might be accounted for, at
      least partially, by deficits in perspective-switching and impaired inhibitory
      control.

PMID- 26216169
TI  - Vascular endothelial growth factor C (VEGF-C) expression predicts metastasis in
      tongue cancer.
AB  - OBJECTIVE: We evaluated predictive factors for cervical lymph node metastasis of
      tongue squamous cell carcinoma (SCC). STUDY DESIGN: We present a retrospective
      analysis of 90 patients with T1-2 N0 SCC who underwent primary excision as
      initial treatment without preoperative radiotherapy or chemotherapy. We examined
      the clinicopathologic factors (gender, age, clinical stage, surgical margin,
      grade of differentiation, lymphatic invasion, tumor depth of invasion, pattern of
      invasion [POI]) and immunohistochemical factors (vascular endothelial growth
      factor [VEGF]-A and VEGF-C expression) to predict the probability of lymph node
      metastasis. RESULTS: The local progression-free 5-year survival rate was 100%.
      Tumor depth of invasion (>=4 mm, P = .022), POI (score >4, P = .000), and VEGF-C
      expression (P = .008) were associated with the lymph node metastasis of tongue
      SCC in a multiple logistic regression analysis (odds ratios [ORs]: 5.075, 17.383,
      and 9.533, respectively). CONCLUSIONS: The local control rate of tongue SCC in
      the early stages has significantly improved as a result of development of
      surgical techniques. On the other hand, we believe that tumor depth of invasion
      (>=4 mm), POI, and VEGF-C expression all need to be considered in the
      preoperative and postoperative planning stages for tongue cancer treatment.

PMID- 26216171
TI  - Synthesis of a Tetrabenzotetraaza[8]circulene by a "Fold-In" Oxidative Fusion
      Reaction.
AB  - Tetrabenzotetraaza[8]circulene (1) has been synthesized in good yield by a "fold
      in" oxidative fusion reaction of a 1,2-phenylene-bridged cyclic tetrapyrrole. X
      ray diffraction analysis of 1 has revealed a planar square structure with a
      central cyclooctatetraene (COT) core that shows little alternation of the bond
      lengths. Despite these structural features, 1 shows aromatic-like character, such
      as sharp absorption bands, high fluorescence quantum yields (Phi(F)=0.55 in THF),
      and a single exponential fluorescence decay with tau(F)=3.8 ns. These
      observations indicate a dominant contribution of an [8]radialene-like pi
      conjugation and hence aromatic character of the local aromatic segments in 1.

PMID- 26216170
TI  - Interobserver agreement in dysplasia grading: toward an enhanced gold standard
      for clinical pathology trials.
AB  - OBJECTIVE: Interobserver agreement in the context of oral epithelial dysplasia
      (OED) grading has been notoriously unreliable and can impose barriers for
      developing new molecular markers and diagnostic technologies. This paper aimed to
      report the details of a 3-stage histopathology review and adjudication process
      with the goal of achieving a consensus histopathologic diagnosis of each biopsy.
      STUDY DESIGN: Two adjacent serial histologic sections of oral lesions from 846
      patients were independently scored by 2 different pathologists from a pool of 4.
      In instances where the original 2 pathologists disagreed, a third, independent
      adjudicating pathologist conducted a review of both sections. If a majority
      agreement was not achieved, the third stage involved a face-to-face consensus
      review. RESULTS: Individual pathologist pair kappa values ranged from 0.251 to
      0.706 (fair-good) before the 3-stage review process. During the initial review
      phase, the 2 pathologists agreed on a diagnosis for 69.9% of the cases. After the
      adjudication review by a third pathologist, an additional 22.8% of cases were
      given a consensus diagnosis (agreement of 2 out of 3 pathologists). After the
      face-to-face review, the remaining 7.3% of cases had a consensus diagnosis.
      CONCLUSIONS: The use of the defined protocol resulted in a substantial increase
      (30%) in diagnostic agreement and has the potential to improve the level of
      agreement for establishing gold standards for studies based on histopathologic
      diagnosis.

PMID- 26216172
TI  - Editorial: Follow the yellow brick road--the compassion deficit debate where to
      from here?

PMID- 26216173
TI  - Oral lichen planus: salival biomarkers cortisol, immunoglobulin A, adiponectin.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic mucocutaneous disease,
      inflammatory and autoimmune in character, in which the pathogenesis is not fully
      understood. Psychological stress has also been implicated in triggering or
      exacerbating the disease. OBJECTIVE: The aim of this study was to evaluate the
      psychological profile, sleep, and salivary biological markers-cortisol,
      immunoglobin A (IgA), and adiponectin - in patients with oral lichen planus
      (OLP). METHODS: The sample consisted of 65 patients (33 with OLP and 32 control
      patients). Patients completed hospital anxiety and depression scales (HADD,
      HADA). Questionnaires were used to assess sleepiness: the Pittsburgh sleep
      quality index (PSQI) and the Epworth sleepiness scale (ESS). A visual analog
      scale (VAS) was used for rating pain. Unstimulated whole saliva was evaluated,
      together with total proteins: cortisol, IgA, and adiponectin. RESULTS: Patients
      with OLP obtained significantly higher HADA and PSQI scores than control subjects
      (P = 0.001, P = 0.012, respectively). Total salivary protein (flow at rest)
      analysis found that total proteins were higher in the OLP group (P = 0.001). In
      the OLP group, IgA was 80.3 +/- 51.3 vs. the control group 48.9 +/- 32.8 (P =
      0.005). Mean cortisol was 0.5 +/- 0.3 MUg/dl in the OLP group vs. 0.4 +/- 0.2
      MUg/dl in the control group (P = 0.010). The OLP group showed a correlation
      between the HADA variable and pain (r = 0.358; P = 0.041), HADD (r = 0.568; P =
      0.001), and PSQI (r = 0.537; P = 0.001). CONCLUSIONS: OLP patients presented
      worse psychological profiles and sleep disturbances, as well as higher values for
      IgA, cortisol, and total proteins than control subjects.

PMID- 26216174
TI  - Development of virtual patient models for permanent implant brachytherapy Monte
      Carlo dose calculations: interdependence of CT image artifact mitigation and
      tissue assignment.
AB  - This work investigates and compares CT image metallic artifact reduction (MAR)
      methods and tissue assignment schemes (TAS) for the development of virtual
      patient models for permanent implant brachytherapy Monte Carlo (MC) dose
      calculations. Four MAR techniques are investigated to mitigate seed artifacts
      from post-implant CT images of a homogeneous phantom and eight prostate patients:
      a raw sinogram approach using the original CT scanner data and three methods
      (simple threshold replacement (STR), 3D median filter, and virtual sinogram)
      requiring only the reconstructed CT image. Virtual patient models are developed
      using six TAS ranging from the AAPM-ESTRO-ABG TG-186 basic approach of assigning
      uniform density tissues (resulting in a model not dependent on MAR) to more
      complex models assigning prostate, calcification, and mixtures of prostate and
      calcification using CT-derived densities. The EGSnrc user-code BrachyDose is
      employed to calculate dose distributions. All four MAR methods eliminate bright
      seed spot artifacts, and the image-based methods provide comparable mitigation of
      artifacts compared with the raw sinogram approach. However, each MAR technique
      has limitations: STR is unable to mitigate low CT number artifacts, the median
      filter blurs the image which challenges the preservation of tissue
      heterogeneities, and both sinogram approaches introduce new streaks. Large local
      dose differences are generally due to differences in voxel tissue-type rather
      than mass density. The largest differences in target dose metrics (D90, V100,
      V150), over 50% lower compared to the other models, are when uncorrected CT
      images are used with TAS that consider calcifications. Metrics found using models
      which include calcifications are generally a few percent lower than prostate-only
      models. Generally, metrics from any MAR method and any TAS which considers
      calcifications agree within 6%. Overall, the studied MAR methods and TAS show
      promise for further retrospective MC dose calculation studies for various
      permanent implant brachytherapy treatments. 

PMID- 26216176
TI  - CDC updates guidelines for treating sexually transmitted diseases.

PMID- 26216175
TI  - Drug Release and Targeting: the Versatility of Polymethacrylate Nanoparticles for
      Peroral Administration Revealed by Using an Optimized In Vitro-Toolbox.
AB  - PURPOSE: The contribution of permeability and drug release to drug targeting were
      investigated in the course of development of a nanosized formulation of the anti
      inflammatory compound TMP-001, for the local treatment in the gastrointestinal
      tract. METHODS: TMP-001 was encapsulated by nanoprecipitation into Eudragit(r) RS
      100. The permeability of these carriers was investigated in an Ussing chamber
      model and the release rate was determined under biorelevant conditions.
      Formulation toxicity and particle-cell-interaction were investigated by flow
      cytometry, fluorescence and electron microscopy. Furthermore, spray drying was
      performed. RESULTS: Effective internalization of Eudragit(r)-nanoparticles into
      cancer cells was demonstrated. A burst release of the nanoparticles implied poor
      interaction of TMP-001 with Eudragit(r). A sustained release (70.5% release after
      30 min compared to 98.0% for the API) was accomplished after spray drying yielded
      an increased particle size. Recovery rate of TMP-001 after spray drying was 94.2
      +/- 5.9%. CONCLUSION: The release of API from polymeric nanoparticles contributes
      profoundly to the in vivo-performance of drug delivery devices in the
      gastrointestinal tract. The impact of drug-polymer interaction and particle size
      was analyzed. Sustained release of TMP-001 could only be achieved by increasing
      particle size. Therefore, biorelevant release testing has been demonstrated to be
      a valid tool for nanoformulation design.

PMID- 26216177
TI  - Preserving sexual function in women and girls with cancer: survivorship is about
      more than just surviving.

PMID- 26216178
TI  - New directions in understanding how the pelvic floor prepares for and recovers
      from vaginal delivery.

PMID- 26216179
TI  - Urine trouble without cranberries?

PMID- 26216180
TI  - Kinetic characterization of the photosynthetic reaction centres in microalgae by
      means of fluorescence methodology.
AB  - The kinetic characterization of the photosynthetic activity in autotrophic
      microalgae plays a key role in the design of optimized photobioreactors. This
      paper presents a procedure to assess kinetic parameters of a three-state
      photosynthetic reaction centres model. Four kinetic parameters of the model were
      assessed by processing the time-series measurements of pulse-amplitude modulation
      fluorimetry. The kinetic parameters were assessed for several microalgal strains
      (Stichococcus bacillaris, Scenedesmus vacuolatus, Chlamydomonas reinhardtii,
      Chlorella vulgaris) growth in vertical and inclined bubble columns and irradiated
      by white-light or red/blue light. The procedure was successfully applied to the
      investigated strains. The assessed parameters allow identifying the irradiance
      range under which: the photochemical process is controlled by the photons
      capture; the photoinhibition competes with the photochemical quenching. The
      analysis of the time-scale of the photosynthetic reaction centres as a function
      of the irradiance allows interpreting the performances of photobioreactors
      characterized by non-homogeneous irradiance. 

PMID- 26216181
TI  - Enhancement of the solubility and stability of D-amino acid oxidase by fusion to
      an elastin like polypeptide.
AB  - An elastin-like polypeptide (ELP) was fused to D-amino acid oxidases (DAAO). ELP
      DAAO exhibited a better solubility in aqueous solutions than DAAO, and its
      enzymatic activity is about 1.6 times that of DAAO. The stability of the proteins
      was investigated by interacting with urea at various concentrations. The circular
      dichroism and fluorescence spectra were measured. The results demonstrated that
      that ELP-DAAO exhibited a much better stability than DAAO, and ELP-DAAO has
      retained the alpha-helix content with a high percentage even at a high urea
      concentration. The results of this work have demonstrated that the ELP tag can be
      utilized to purify DAAO, in the meantime the solubility and stability of the
      enzyme are improved.

PMID- 26216182
TI  - Quality-by-Design approach to monitor the operation of a batch bioreactor in an
      industrial avian vaccine manufacturing process.
AB  - Monitoring batch bioreactors is a complex task, due to the fact that several
      sources of variability can affect a running batch and impact on the final product
      quality. Additionally, the product quality itself may not be measurable on line,
      but requires sampling and lab analysis taking several days to be completed. In
      this study we show that, by using appropriate process analytical technology
      tools, the operation of an industrial batch bioreactor used in avian vaccine
      manufacturing can be effectively monitored as the batch progresses. Multivariate
      statistical models are built from historical databases of batches already
      completed, and they are used to enable the real time identification of the
      variability sources, to reliably predict the final product quality, and to
      improve process understanding, paving the way to a reduction of final product
      rejections, as well as to a reduction of the product cycle time. It is also shown
      that the product quality "builds up" mainly during the first half of a batch,
      suggesting on the one side that reducing the variability during this period is
      crucial, and on the other side that the batch length can possibly be shortened.
      Overall, the study demonstrates that, by using a Quality-by-Design approach
      centered on the appropriate use of mathematical modeling, quality can indeed be
      built "by design" into the final product, whereas the role of end-point product
      testing can progressively reduce its importance in product manufacturing. 

PMID- 26216183
TI  - Using Agent-Based Models to Address "Wicked Problems" Like Tobacco Use: A Report
      From the Institute of Medicine.

PMID- 26216184
TI  - A focused ion beam milling and lift-out approach for site-specific preparation of
      frozen-hydrated lamellas from multicellular organisms.
AB  - Cryo-electron tomography provides 3D views of cellular architecture with
      molecular resolution. A principal limitation of cryo-transmission electron
      microscopy performed on cells or tissues is the accessible specimen thickness.
      Recently it has been shown that cryo-focused ion beam milling of plunge-frozen
      eukaryotic cells can produce homogeneously thin, distortion free lamellas for
      cryo-electron tomography. Multicellular organisms and tissue cannot be properly
      vitrified and thinned using this technique because they are considerably thicker.
      High pressure freezing is therefore necessary to provide optimal preservation.
      Here, we describe a workflow for preparing lamellas from Caenorhabditis elegans
      worms using cryo-FIB applied to high pressure frozen samples. We employ cryo
      planing followed by correlative cryo-fluorescence microscopy to navigate this
      large multicellular volume and to localize specific targets within. To produce
      vitreous lamellas amenable to cryo-TEM observations at these targeted locations,
      we have developed a dedicated lift-out procedure at cryogenic temperature. 

PMID- 26216185
TI  - Risk factors associated with severe influenza virus infections in hospitalized
      children during the 2013 to 2014 season.
AB  - BACKGROUND: An outbreak of influenza virus infection occurred in Taiwan from
      October 2013 to May 2014. We conducted a clinical study to identify risk factors
      associated with severe influenza virus infections in children. METHODS: During
      the outbreak period, data from 110 hospitalized children with influenza virus
      infection were collected. We analyzed the data, the need for intensive care, and
      patient outcome to identify clinical features and risk factors of severe
      infections, defined as the need of intensive care. RESULTS: Of the 110
      inpatients, there were 57 male and 53 female patients; the median age was 2.6
      (interquartile range, 1.0-6.3) years. Nineteen patients required intensive care
      and two patients died. Children who were underweight (p = 0.01) or those with
      neuromuscular disease (p = 0.007) and digestive tract disease (p = 0.03) were
      prone to severe infection. Occurrence of seizure (p = 0.004), conscious
      disturbance (p = 0.02), or low oxygen saturation at admission (p = 0.04)
      predicted the need for intensive care. Higher initial absolute neutrophil count
      (p = 0.02) and patch or pleural effusion on chest X-ray examination (p = 0.02)
      were associated with severe infection. In the multivariable analysis, digestive
      tract disease [p = 0.03; adjusted odds ratio (OR), 12.37; 95% confidence interval
      (CI), 1.28-119.43], seizure (p = 0.001; adjusted OR, 49.54; 95% CI, 4.61-532.76)
      and conscious disturbance (p = 0.006; adjusted OR, 131.61; 95% CI, 4.18-4141.64)
      were most significantly associated with severe influenza virus infection.
      CONCLUSION: Close monitoring of the important risk factors including underlying
      digestive tract diseases, seizure attack and conscious disturbance were
      recommended during the influenza season.

PMID- 26216186
TI  - Proficiency testing for the detection of anti-citrullinated protein antibody in
      China.
AB  - BACKGROUND: Anti-citrullinated protein antibodies (ACPAs) are important for the
      detection of rheumatoid arthritis (RA). There are many laboratories to detect it
      in their routine work, but their performance is not displayed in China. To
      examine the performance of ACPA assays from all laboratories, it is necessary to
      organize a laboratory proficiency test (PT). METHODS: A panel of 5 samples,
      including 4 positive and 1 negative, was produced by the National Center for
      Clinical Laboratories, using serum derived from patients, then distributed to 271
      clinical laboratories. Quantitative and qualitative results reported by the
      participating laboratories were compared. RESULTS: Overall, 80.97% (200/247) of
      the laboratories had eligible PT scores. Of the kits used, most ELISA and
      chemiluminescence kits had a high sensitivity and specificity. Regarding intra
      assay discrepancy, the Roche and Abbott kit had a better variable coefficient.
      The ratios of the quantitative results to the kit-specific cut-off values were
      similar. CONCLUSION: Performance varied between laboratories. Reagents and
      methods are the most important factors. Other factors may affect the intra-assay
      discrepancy. The similar mean of ratios of the quantitative results to the kit
      assigned cut-offs suggests that a national criterion is requisite. It is
      necessary to organize a PT to identify performances of different laboratories.

PMID- 26216187
TI  - Digital gene expression analysis of transcriptomes in lipopolysaccharide-induced
      acute respiratory distress syndrome.
AB  - BACKGROUND: The mortality from acute respiratory distress syndrome (ARDS) is
      high, and its exact pathogenesis remains unclear, which forms a major obstacle
      for prevention and treatment of this disease. In the present study, we used
      digital gene expression (DGE) to detect the differentially expressed genes of the
      lung at 4h after lipopolysaccharide (LPS) exposure in a mouse model. METHODS:
      Mice were treated with LPS or control saline by intratracheal instillation for
      4h, and their lung tissues were collected for DGE analysis. We used a false
      discovery rate <=0.001 and an absolute value of the log2 ratio>=1 as the
      thresholds for judging the significance of any difference in gene expression
      between the two members of each pair of mice. RESULTS: We obtained 3,387,842
      clean tags (i.e., after filtering to remove potentially erroneous tags) and about
      84,513 corresponding distinct clean tags (i.e., types of tag). Approximately
      91.20% of the clean tags could be mapped, and 82.71% could be uniquely mapped, to
      the reference tags, and 3.82% were unknown tags. At least 2200 differentially
      expressed genes were identified and analyzed for enrichment of Gene Ontology and
      Kyoto Encyclopedia of Genes and Genomes pathway. Twenty genes with the greatest
      difference in expression levels between the two members of every pair of mice
      were chosen. The majority of these genes are involved in signaling transduction,
      molecular adhesion, and metabolic pathways. CONCLUSIONS: Using the powerful
      technology of DGE, we present, to our knowledge, the first in-depth
      transcriptomic analysis of mouse lungs after LPS exposure. We found some
      differentially expressed genes that might play important roles in the
      pathogenesis of ARDS.

PMID- 26216188
TI  - The effect of hemolysis, icterus and lipemia on Randox immunoturbidimetric
      adiponectin assay.

PMID- 26216189
TI  - Transactivation of human osteoprotegerin promoter by GATA-3.
AB  - Osteoprotegerin (OPG) is a key regulator of bone remodeling. Mutations in OPG are
      involved in a variety of human diseases. We have shown that cochlear spiral
      ganglion cells secrete OPG at high levels and lack of OPG causes sensorineural
      hearing loss in addition to the previously described conductive hearing loss. In
      order to study the regulation of OPG expression, we conducted a database search
      on regulatory elements in the promoter region of the OPG gene, and identified two
      potential GATA-3 binding sites. Using luciferase assays and site directed
      mutagenesis, we demonstrate that these two elements are GATA-3 responsive and
      support GATA-3 transactivation in human HEK and HeLa cells. The expression of
      wild type GATA-3 activated OPG mRNA and protein expression, while the expression
      of a dominant negative mutant of GATA-3 or a GATA-3 shRNA construct reduced OPG
      mRNA and protein levels. GATA-3 deficient cells generated by expressing a GATA-3
      shRNA construct were sensitive to apoptosis induced by etoposide and TNF-alpha.
      This apoptotic effect could be partly prevented by the co-treatment with
      exogenous OPG. Our results suggest new approaches to rescue diseases due to GATA
      3 deficiency - such as in hypoparathyroidism, sensorineural deafness, and renal
      (HDR) syndrome - by OPG therapy. 

PMID- 26216191
TI  - Evolving concepts in tumour lysis syndrome management.

PMID- 26216192
TI  - Functional Networks of Highest-Connected Splice Isoforms: From The Chromosome 17
      Human Proteome Project.
AB  - Alternative splicing allows a single gene to produce multiple transcript-level
      splice isoforms from which the translated proteins may show differences in their
      expression and function. Identifying the major functional or canonical isoform is
      important for understanding gene and protein functions. Identification and
      characterization of splice isoforms is a stated goal of the HUPO Human Proteome
      Project and of neXtProt. Multiple efforts have catalogued splice isoforms as
      "dominant", "principal", or "major" isoforms based on expression or evolutionary
      traits. In contrast, we recently proposed highest connected isoforms (HCIs) as a
      new class of canonical isoforms that have the strongest interactions in a
      functional network and revealed their significantly higher (differential)
      transcript-level expression compared to nonhighest connected isoforms (NCIs)
      regardless of tissues/cell lines in the mouse. HCIs and their expression behavior
      in the human remain unexplored. Here we identified HCIs for 6157 multi-isoform
      genes using a human isoform network that we constructed by integrating a large
      compendium of heterogeneous genomic data. We present examples for pairs of
      transcript isoforms of ABCC3, RBM34, ERBB2, and ANXA7. We found that functional
      networks of isoforms of the same gene can show large differences. Interestingly,
      differential expression between HCIs and NCIs was also observed in the human on
      an independent set of 940 RNA-seq samples across multiple tissues, including
      heart, kidney, and liver. Using proteomic data from normal human retina and
      placenta, we showed that HCIs are a promising indicator of expressed protein
      isoforms exemplified by NUDFB6 and M6PR. Furthermore, we found that a significant
      percentage (20%, p = 0.0003) of human and mouse HCIs are homologues, suggesting
      their conservation between species. Our identified HCIs expand the repertoire of
      canonical isoforms and are expected to facilitate studying main protein products,
      understanding gene regulation, and possibly evolution. The network is available
      through our web server as a rich resource for investigating isoform functional
      relationships (http://guanlab.ccmb.med.umich.edu/hisonet). All MS/MS data were
      available at ProteomeXchange Web site (http://www.proteomexchange.org) through
      their identifiers (retina: PXD001242, placenta: PXD000754).

PMID- 26216193
TI  - Genotype-phenotype correlations in 5-fluorouracil metabolism: a candidate DPYD
      haplotype to improve toxicity prediction.
AB  - 5-Fluorouracil is among the most widely used anticancer drug, but a fraction of
      treated patients develop severe toxicity, with potentially lethal injuries. The
      predictive power of the available pretreatment assays, used to identify patients
      at risk of severe toxicity, needs improvements. This study aimed to correlate a
      phenotypic marker of 5-fluorouracil metabolism (the individual degradation rate
      of 5-fluorouracil-5-FUDR) with 15 functional polymorphisms in the
      dihydropyrimidine dehydrogenase gene (DPYD). Single SNP (single-nucleotide
      polymorphism) analysis revealed that the SNPs rs1801160, rs1801265, rs2297595 and
      rs3918290 (splice site variant IVS14+1G>A) were significantly associated with a
      decreased value of 5-FUDR, and the rs3918290 causing the larger decrease. Multi
      SNP analysis showed that a three-SNP haplotype (Hap7) involving rs1801160,
      rs1801265 and rs2297595 causes a marked decrease in 5-FUDR, comparable to that
      caused by the splice site variant rs3918290, which is the main pharmacogenetic
      marker associated with severe fluorouracil toxicity. The similar effect played by
      Hap7 and by the splice site variant rs3918290 upon individual 5-FUDR suggests
      that Hap7 could also represent a similar determinant of fluorouracil toxicity.
      Haplotype assessment could improve the predictive value of DPYD genetic markers
      aimed at the pre-emptive identification of patients at risk of severe 5
      fluorouracil toxicity.The Pharmacogenomics Journal advance online publication, 28
      July 2015; doi:10.1038/tpj.2015.56.

PMID- 26216194
TI  - Hydration amongst nurses and doctors on-call (the HANDS on prospective cohort
      study).
AB  - BACKGROUND & AIMS: Dehydration of as little 2% of total body weight may impair
      physical and cognitive performance. The aim of this study was to investigate the
      prevalence of dehydration at the start and end of shifts in nurses and doctors on
      call. The secondary aims were to assess the relation between hydration status and
      cognitive function. METHODS: This prospective cohort study was conducted on
      nurses and doctors working on medical and surgical admissions wards at a
      university teaching hospital. Participants arrived on the ward approximately 20
      min before their shift and were asked to provide a urine sample. Height and
      weight were then measured. A 10 mL blood sample was analysed for full blood
      count, serum urea and electrolytes, and blood glucose. Cognitive function was
      assessed using a series of computer-based tests including the Stroop Colour
      Naming Interference Test and Sternberg Memory Paradigm. Participants then worked
      normally but were asked to keep a fluid diary for the duration of their shift and
      fluid balance was estimated. Tests were repeated at the end of the shift.
      Dehydration was defined as urine osmolality >800 mOsmol/kg and oliguria was
      defined as urine output <0.5 ml/kg/hour. RESULTS: We recruited 92 nurses and
      doctors, of whom 88 completed the study, amounting to 130 shifts. 52%
      participated for one shift, and 48% for two shifts. Thirty-six percent of
      participants were dehydrated at the start of the shift and 45% were dehydrated at
      the end of their shift. Mean (SD) urinary osmolality was significantly greater at
      the end of the shift when compared with the start [720 (282) vs. 622 (297)
      mOsm/kg, P = 0.031). Moreover, 41% were oliguric at the end of the shift. Single
      number and five-letter Sternberg short-term memory tests were significantly
      impaired in dehydrated participants (P < 0.05). CONCLUSIONS: This study
      highlights that a significant proportion of nurses and doctors were dehydrated at
      the start and end of medical and surgical shifts. Dehydration was associated with
      some impairment of cognitive function.

PMID- 26216195
TI  - Effects of combination of whey protein intake and rehabilitation on muscle
      strength and daily movements in patients with hip fracture in the early
      postoperative period.
AB  - BACKGROUND & AIMS: Elderly patients can be at risk of protein catabolism and
      malnutrition in the early postoperative period. Whey protein includes most
      essential amino acids and stimulates the synthesis of muscle protein. The purpose
      of this study was to investigate the effect of resistance training in combination
      with whey protein intake in the early postoperative period. METHODS: We
      randomized patients to a whey protein group or a control group. The former group
      received 32.2 g of whey protein pre- and post-rehabilitation in the early
      postoperative period for two weeks. Outcomes were knee extension strength on
      either side by Biodex 4.0, and the ability of transfer, walking, toilet use and
      stair use by the Barthel Index (BI). We performed initial and final assessments
      in the second and tenth rehabilitation sessions. RESULTS: A total of 38 patients
      were recruited: 20 in the whey protein group and 18 in the control group.
      Participants in the whey protein group showed significantly greater improvement
      in knee extension strength in the operated limb compared with the control group
      (F = 6.11, P = 0.02). The non-operated limb also showed a similar tendency (F =
      3.51, P = 0.07). The abilities of transfer, walking and toilet use showed greater
      improvements in the whey protein group than in the control group by BI (P <
      0.05). CONCLUSION: The combination of whey protein intake and rehabilitation for
      two weeks in the early postoperative period has a beneficial effect on knee
      extension strength in both lower limbs and BI (transfer, walking and toilet use)
      scores in patients with hip fracture.

PMID- 26216196
TI  - Proposal of a genetic classifier for risk group stratification in pediatric T
      cell lymphoblastic lymphoma reveals differences from adult T-cell lymphoblastic
      leukemia.

PMID- 26216198
TI  - Chemosensory discrimination of identity and familiarity in koalas.
AB  - Despite numerous descriptive accounts of scent marking in marsupials, rigorous
      experimentation is rare, and relatively little evidence exists to show that
      conspecifics use chemical signals to distinguish between individuals or different
      social groups. In this study a series of olfactory discrimination tests sought to
      determine whether: (1) male koala sternal scent gland secretions are individually
      distinctive; and (2) male koalas can differentiate between the scent of familiar
      and unfamiliar individuals. In the first experiment a habituation-discrimination
      trial demonstrated that male koalas discriminate between the scent gland
      secretions of different unfamiliar individuals. In a second experiment male
      koalas spent significantly more time investigating scent from unfamiliar males
      than familiar males, supporting the hypothesis that they differentiate between
      conspecifics based on their familiarity. Taken together these results suggest
      that male koalas are able to discriminate the identity and familiarity of
      conspecifics using chemical cues, and provide a platform for further studies
      investigating the functional role of olfactory communication in this species. 

PMID- 26216197
TI  - Contribution of JAK2 mutations to T-cell lymphoblastic lymphoma development.
AB  - The JAK-STAT pathway has a substantial role in lymphoid precursor cell
      proliferation, survival and differentiation. Nonetheless, the contribution of
      JAK2 to T-cell lymphoblastic lymphoma (T-LBL) development remains poorly
      understood. We have identified one activating TEL-JAK2 translocation and four
      missense mutations accumulated in 2 out of 16 T-LBL samples. Two of them are
      novel JAK2 mutations and the other two are reported for the first time in T-LBL.
      Notably, R683G and I682T might have arisen owing to RNA editing. Mutated samples
      showed different mutated transcripts suggesting sub-clonal heterogeneity.
      Functional approaches revealed that two JAK2 mutations (H574R and R683G)
      constitutively activate JAK-STAT signaling in gamma2A cells and can drive the
      proliferation of BaF3-EpoR cytokine-dependent cell line. In addition, aberrant
      hypermethylation of SOCS3 might contribute to enhance the activation of JAK-STAT
      signaling. Of utmost interest is that primary T-LBL samples harboring JAK2
      mutations exhibited increased expression of LMO2, suggesting a mechanistic link
      between JAK2 mutations and the expression of LMO2, which was confirmed for the
      four missense mutations in transfected gamma2A cells. We therefore propose that
      active JAK2 contribute to T-LBL development by two different mechanisms, and that
      the use of pan-JAK inhibitors in combination with epigenetic drugs should be
      considered in future treatments. 

PMID- 26216199
TI  - Studies of the extracytoplasmic function sigma factor PG0162 in Porphyromonas
      gingivalis.
AB  - PG0162, annotated as an extracytoplasmic function (ECF) sigma factor in
      Porphyromonas gingivalis, is composed of 193 amino acids. As previously reported,
      the PG0162-deficient mutant, P. gingivalis FLL350 showed significant reduction in
      gingipain activity compared with the parental strain. Because this ECF sigma
      factor could be involved in the virulence regulation in P. gingivalis, its
      genetic properties were further characterized. A 5'-RACE analysis showed that the
      start of transcription of the PG0162 gene occurred from a guanine (G) residue 69
      nucleotides upstream of the ATG translation initiation codon. The function of
      PG0162 as a sigma factor was confirmed in a run-off in vitro transcription assay
      using the purified rPG0162 and RNAP core enzyme from Escherichia coli with the
      PG0162 promoter as template. As an appropriate PG0162 inducing environmental
      signal is unknown, a strain overexpressing the PG0162 gene designated P.
      gingivalis FLL391 was created. Compared with the wild-type strain, transcriptome
      analysis of P. gingivalis FLL391 showed that approximately 24% of the genome
      displayed altered gene expression (260 upregulated genes; 286 downregulated
      genes). Two other ECF sigma factors (PG0985 and PG1660) were upregulated more
      than two-fold. The autoregulation of PG0162 was confirmed with the binding of the
      rPG0162 protein to the PG0162 promoter in electrophoretic mobility shift assay.
      In addition, the rPG0162 protein also showed the ability to bind to the promoter
      region of two genes (PG0521 and PG1167) that were most upregulated in P.
      gingivalis FLL391. Taken together, our data suggest that PG0162 is a sigma factor
      that may play an important role in the virulence regulatory network in P.
      gingivalis.

PMID- 26216200
TI  - Increased rainfall variability and N addition accelerate litter decomposition in
      a restored prairie.
AB  - Anthropogenic nitrogen deposition and projected increases in rainfall variability
      (the frequency of drought and heavy rainfall events) are expected to strongly
      influence ecosystem processes such as litter decomposition. However, how these
      two global change factors interact to influence litter decomposition is largely
      unknown. I examined how increased rainfall variability and nitrogen addition
      affected mass and nitrogen loss of litter from two tallgrass prairie species,
      Schizachyrium scoparium and Solidago canadensis, and isolated the effects of each
      during plant growth and during litter decomposition. I increased rainfall
      variability by consolidating ambient rainfall into larger events and simulated
      chronic nitrogen deposition using a slow-release urea fertilizer. S. scoparium
      litter decay was more strongly regulated by the treatments applied during plant
      growth than by those applied during decomposition. During plant growth, increased
      rainfall variability resulted in S. scoparium litter that subsequently decomposed
      more slowly and immobilized more nitrogen than litter grown under ambient
      conditions, whereas nitrogen addition during plant growth accelerated subsequent
      mass loss of S. scoparium litter. In contrast, S. canadensis litter mass and N
      losses were enhanced under either N addition or increased rainfall variability
      both during plant growth and during decomposition. These results suggest that
      ongoing changes in rainfall variability and nitrogen availability are
      accelerating nutrient cycling in tallgrass prairies through their combined
      effects on litter quality, environmental conditions, and plant community
      composition. 

PMID- 26216201
TI  - Robust interface between flying and topological qubits.
AB  - Hybrid architectures, consisting of conventional and topological qubits, have
      recently attracted much attention due to their capability in consolidating
      robustness of topological qubits and universality of conventional qubits.
      However, these two kinds of qubits are normally constructed in significantly
      different energy scales, and thus the energy mismatch is a major obstacle for
      their coupling, which can support the exchange of quantum information between
      them. Here we propose a microwave photonic quantum bus for a strong direct
      coupling between the topological and conventional qubits, where the energy
      mismatch is compensated by an external driving field. In the framework of tight
      binding simulation and perturbation approach, we show that the energy splitting
      of Majorana fermions in a finite length nanowire, which we use to define
      topological qubits, is still robust against local perturbations due to the
      topology of the system. Therefore, the present scheme realizes a rather robust
      interface between the flying and topological qubits. Finally, we demonstrate that
      this quantum bus can also be used to generate multipartitie entangled states with
      the topological qubits. 

PMID- 26216202
TI  - Formation of ortho-cyano-aminothiophenolate ligands with versatile binding modes
      via facile carbon-sulfur bond cleavage of 2-aminobenzothiazoles at mercury(II)
      centres.
AB  - Addition of 2-aminobenzothiazole and substituted derivatives to mercuric acetate
      in warm ethanol leads to the high yield formation of [Hg{SC6H3XN(C[triple bond,
      length as m-dash]N)}]n resulting from loss of hydrogen and sulfur-carbon bond
      cleavage. Addition of phosphines affords a series of complexes in which the new
      ortho-cyano-aminothiophenolate ligands adopt three different binding modes. 

PMID- 26216203
TI  - Photoinduced Carbon Monoxide Release from Half-Sandwich Iron(II) Carbonyl
      Complexes by Visible Irradiation: Kinetic Analysis and Mechanistic Investigation.
AB  - Three half-sandwich iron(II) complexes, [Fe(eta(5) -Cp)(cis-CO)2 X] (X(-) =Cl(-)
      , Br(-) , I(-) ), were synthesized and characterized. The kinetics of the CO
      releasing behaviour of these complexes upon illumination by visible irradiation
      in various media was investigated. Our results indicated that the CO release was
      significantly affected by the auxiliary ligands. Of the three light sources used
      (blue, green, and red), blue light exhibited the highest efficiency. In the
      photoinduced CO release, the solvents and exogenous nucleophiles in the media
      were involved, which allowed their CO-releasing reaction to comply with pseudo
      first-order model rather than the characteristic zero-order model for a
      photochemical reaction. In aqueous media (D2 O), an intermediate bearing the core
      of {Fe(II) (cis-CO)2 } involving cleavage of cyclopentadiene was detected.
      Despite the non-absorption of the red light, its illumination combined with
      nucleophilic substitution did cause considerable CO release. Assessment of the
      cytotoxicity of the three complexes indicated that they showed good
      biocompatibility. 

PMID- 26216204
TI  - Analysis of Bone Height Changes after Maxillary Sinus Augmentation with
      Simultaneous and Delayed Placement of Dental Implants: A Clinical and
      Radiographic Study.
AB  - PURPOSE: To retrospectively assess the changes of the vertical height of the
      maxillary sinus floor after augmentation with simultaneous and delayed placement
      of implants. MATERIALS AND METHODS: In total, 38 patients with 76 implants were
      involved; vertical bone height of the sinus floor was radiographically measured
      at different stages including preoperation, immediately postsurgery, 6 and 12
      months postsurgery, and 6 and 24 months postfunctional loading. RESULTS: Sinus
      augmentation significantly increased vertical bone height of the sinus floor for
      both the simultaneous and delayed groups. The survival rate was 100% in the
      simultaneous group and 95.46% in the delayed group. For simultaneous placement,
      the vertical bone height of the sinus floor at 6 and 12 months postsurgery was
      significantly less than that immediately postsurgery. For both groups, augmented
      bone height of the sinus floor showed significant decrease from 6 months to 24
      months postfunctional loading. The mean value of final bone augmentation was 5.85
      mm for simultaneous placement and 5.80 mm for delayed placements. CONCLUSION:
      Sinus augmentation with simultaneous and delayed placement of implants led to
      similar survival rates and bone augmentation. Resorption of augmentative bone was
      evident at 24 months postfunctional loading in both cases.

PMID- 26216205
TI  - Sensing the energetic status of plants and ecosystems.
AB  - The emerging consistency of the relationship between biochemical, optical, and
      odorous signals emitted by plants and ecosystems offers promising prospects for
      continuous local and global monitoring of the energetic status of plants and
      ecosystems, and therefore of their processing of energy and matter. 

PMID- 26216206
TI  - A new approach towards the synthesis of drospirenone and steroidal spirolactones.
AB  - A general methodology for the synthesis of different steroidal 17-spirolactones
      is described. This method uses lithium acetylide of ethyl propiolate as the three
      carbon synthon and the method was successfully applied for the process
      development of drospirenone. 

PMID- 26216207
TI  - Variance of spinal osteoporosis induced by dexamethasone and methylprednisolone
      and its associated mechanism.
AB  - BACKGROUND: Glucocorticoid (GC) administration is the most common cause of
      secondary osteoporosis. Previous studies investigated GCs dose and frequency
      correlated positively with the side effects of glucocorticoid on bone health,
      however the impaired effect of various types of GCs on bone has not yet been
      reported. PURPOSE: The aim is to compare the effect of long-acting
      (dexamethasone) and relatively short-acting glucocorticoid (methylprednisolone)
      on rat lumbar spine and try to explore the associated mechanism. METHOD: Sprague
      Dawley rats (N=48) were randomly divided into four groups: baseline group (BL),
      control group (CON), methylprednisolone group (MP) and dexamethasone group
      (DEXA). BL rats were euthanized to remain as baseline (M0) at the beginning of
      experiment. CON group were injected daily with vehicle, while the other groups
      were given a daily subcutaneous injection of 1mg/kg methylprednisolone and were
      given a subcutaneous injection of 0.6mg/kg dexamethasone per 3days, respectively.
      CON, MP and DEXA groups were monitored at 4th week (M1), 8th week (M2) and 12th
      week (M3) after intervention. Dual-energy X-ray, micro-computed tomography,
      compressive test, enzyme-linked immunosorbent assay have been used for bone
      mineral density, microarchitecture, biomechanical property of vertebrae and
      levels of estrogen, PINP and beta-CTX, respectively. mRNA expression analysis of
      Biglycan, Col1a1, MMP9, Cathepsin K, Runx2, OPG, LRP5, Sclerostin were performed.
      RESULT: We found that the bone mineral density (BMD) was significantly lower in
      DEXA rats at M3 compared with MP rats. The relative surface and trabecular number
      were significantly lower in DEXA group than that in MP group at M2, while
      trabecular separation was significantly higher in DEXA group than that in MP
      group at the same point. The compressive strength was significantly lower in L4
      of DEXA than that in MP rats at M2 and M3. The levels of both PINP and estradiol
      in DEXA group were lower than MP group at M3, even though without statistical
      significance. The expression of bone formation marker Runx2 was significantly
      down-regulated at M3 in DEXA group compared with MP, CON and BL groups, while the
      expression of Col1a1 was significantly up-regulated and biglycan, LRP-5, OPG were
      significantly down-regulated in GCs intervention groups compared with CON and BL
      groups. There were no statistical differences in MMP9, Cathepsin K, Sclerostin
      among CON, MP and DEXA groups. CONCLUSION: These results indicate that
      dexamethasone, the long-acting glucocorticoid, generates more serious
      osteoporosis of rat lumbar spine than methylprednisolone, which is relatively
      short-acting glucocorticoid. The discrepancy between the two GCs inducing
      osteoporosis may be mainly caused by a decrease in bone formation. RUNX2 and
      Col1a1 may be the two of critical genes inducing the discrepant impairment.

PMID- 26216208
TI  - Lithocholic acid and derivatives: Antibacterial activity.
AB  - In order to develop bioactive lithocholic acid derivatives, we prepared fifteen
      semi-synthetic compounds through modification at C-3 and/or C-24. The reactions
      showed yields ranging from 37% to 100%. The structures of all compounds obtained
      were identified on the basis of their spectral data (IR, MS, 1D- and 2D-NMR). The
      activity of lithocholic acid and derivatives was evaluated against the growth of
      Escherichia coli, Staphylococcus aureus, Bacillus cereus and Pseudomonas
      aeruginosa. The derivative 3alpha-formyloxy-5beta-cholan-24-oic acid (LA-06)
      showed the best activity, with MIC values of 0.0790 mM against E. coli (Ec 27)
      and B. cereus in both cases, and 0.0395 mM against S. aureus (ATCC 12692).
      Lithocholic acid and the derivatives with MIC?1.2 mM were evaluated on the
      susceptibility of some bacterial pathogens to the aminoglycoside antibiotics
      neomycin, amikacin and gentamicin was evaluated. There are no previously reported
      studies about these compounds as modifiers of the action of antibiotics or any
      other drugs.

PMID- 26216209
TI  - Benign prostatic enlargement is not associated with diabetes: a population-based
      study.
AB  - The association between diabetes and benign prostatic hyperplasia remains
      inconclusive. In this case-control study, we examined the association of diabetes
      with benign prostatic enlargement (BPE) using the Longitudinal Health Insurance
      Database 2000 in Taiwan. In total, 20 152 patients with BPE as cases and 20 152
      age-matched patients without BPE were included as controls. Conditional logistic
      regression analyses were performed to calculate the odds ratio (OR) and
      corresponding 95% CI for having been previously diagnosed with diabetes between
      cases and controls. We found that of the 40 304 sampled patients, 9492 (23.6%)
      had a history of diabetes before the index date. This mean age for the sampled
      patients was 65.9 with a standard deviation of 12.0 years. A Chi-squared test
      revealed that there was a significant difference in the prevalence of prior
      diabetes between cases and controls (25.3% vs. 21.8%, p < 0.001). The conditional
      logistic regression found that the OR of prior diabetes for cases was 1.21 (95%
      CI = 1.15-1.27) compared with controls. However, after adjusting for geographic
      region, monthly income, urbanization level, hypertension, coronary heart disease
      (CHD), hyperlipidemia, tobacco use disorder, and obesity, the association between
      prior diabetes and BPE did not reach a statistically significant level (OR =
      1.03, 95% CI = 0.98-1.08). In addition, it was noteworthy that hypertension (OR =
      1.25, 95% CI = 1.20-1.31), CHD (OR = 1.40, 95% CI = 1.32-1.48), and
      hyperlipidemia (OR = 1.30, 95% CI = 1.24-1.36) were all significantly associated
      with BPE. We found that men with a diagnosis of diabetes were not significantly
      associated with BPE after adjusting for patient's sociodemographic
      characteristics and comorbidities. 

PMID- 26216210
TI  - Elevated levels of Th17 cells in children with central obesity.
AB  - BACKGROUND: It is believed that the recently discovered interleukin 17-producing
      Th17 cells play a role in the pathogenesis of chronic inflammation in the course
      of obesity and diabetes. OBJECTIVES: The purpose of our study was to complete
      data on this subject in children. METHODS: We assessed Th17 cell levels in the
      peripheral blood of children diagnosed with central obesity (n = 14) and compared
      the results with data obtained in patients with newly diagnosed (n = 11) and long
      term type 1 diabetes mellitus (n = 18), and in a control group as well (n = 24).
      RESULTS: (i) Children with central obesity were characterized by higher
      percentages of Th17 cells as compared to children from the control group; (ii) in
      the peripheral blood of patients with long-term type 1 diabetes the Th17 cell
      counts were higher compared to the control group; (iii) total plasma cholesterol
      concentration correlated positively with Th17/Treg cells ratio; and (iv) among
      patients with long-term diabetes, disease duration correlated positively with
      Th17 cell count and Th17/Th1 cell ratio. CONCLUSION: The results of our study
      indicate that Th17 cells may be involved in chronic inflammation accompanying
      obesity and type 1 diabetes mellitus in children.

PMID- 26216211
TI  - The impact of sleep on age-related sarcopenia: Possible connections and clinical
      implications.
AB  - Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass,
      strength and function, leading to the risk of multiple adverse outcomes,
      including death. Its pathophysiology involves neuroendocrine and inflammatory
      factors, unfavorable nutritional habits and low physical activity. Sleep may play
      a role in muscle protein metabolism, although this hypothesis has not been
      studied extensively. Reductions in duration and quality of sleep and increases in
      prevalence of circadian rhythm and sleep disorders with age favor proteolysis,
      modify body composition and increase the risk of insulin resistance, all of which
      have been associated with sarcopenia. Data on the effects of age-related slow
      wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea
      (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal
      (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder
      interventions may affect muscle loss. Recent research associating OSA with the
      risk of conditions closely related to the sarcopenia process, such as frailty and
      sleep quality impairment, indirectly suggest that sleep can influence skeletal
      muscle decline in the elderly. Several protein synthesis and degradation pathways
      are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1),
      testosterone, cortisol and insulin, which act on the cellular and molecular
      levels to increase or reestablish muscle fiber, strength and function. Age
      related sleep problems potentially interfere intracellularly by inhibiting
      anabolic hormone cascades and enhancing catabolic pathways in the skeletal
      muscle. Specific physical exercises combined or not with nutritional
      recommendations are the current treatment options for sarcopenia. Clinical
      studies testing exogenous administration of anabolic hormones have not yielded
      adequate safety profiles. Therapeutic approaches targeting sleep disturbances to
      normalize circadian rhythms and sleep homeostasis may represent a novel strategy
      to preserve or recover muscle health in older adults. Promising research results
      regarding the associations between sleep variables and sarcopenia biomarkers and
      clinical parameters are required to confirm this hypothesis.

PMID- 26216212
TI  - Parental intimate partner homicide and its consequences for children: protocol
      for a population-based study.
AB  - BACKGROUND: The loss of a parent due to intimate partner homicide has a major
      impact on children. Professionals involved have to make far-reaching decisions
      regarding placement, guardianship, mental health care and contact with the
      perpetrating parent, without an evidence base to guide these decisions. We
      introduce a study protocol to a) systematically describe the demographics,
      circumstances, mental health and wellbeing of children bereaved by intimate
      partner homicide and b) build a predictive model of factors associated with
      children's mental health and wellbeing after intimate partner homicide.
      METHODS/DESIGN: This study focuses on children bereaved by parental intimate
      partner homicide in the Netherlands over a period of 20 years (1993 - 2012). It
      involves an incidence study to identify all Dutch intimate partner homicide cases
      between 1993 and 2012 by which children have been bereaved; systematic case
      reviews to describe the demographics, circumstances and care trajectories of
      these children; and a mixed-methods study to assess mental health, wellbeing, and
      experiences regarding decisions made and care provided. DISCUSSION: Clinical
      experience and initial research suggest that the children involved often need
      long-term intensive mental health and case management. The costs of these
      services are extensive and the stakes are high. This study lays the foundation
      for an international dataset and evidence-informed decision making.

PMID- 26216214
TI  - Development and validation of the BRIGHTLIGHT Survey, a patient-reported
      experience measure for young people with cancer.
AB  - BACKGROUND: Patient experience is increasingly used as an indicator of high
      quality care in addition to more traditional clinical end-points. Surveys are
      generally accepted as appropriate methodology to capture patient experience. No
      validated patient experience surveys exist specifically for adolescents and young
      adults (AYA) aged 13-24 years at diagnosis with cancer. This paper describes
      early work undertaken to develop and validate a descriptive patient experience
      survey for AYA with cancer that encompasses both their cancer experience and age
      related issues. We aimed to develop, with young people, an experience survey
      meaningful and relevant to AYA to be used in a longitudinal cohort study
      (BRIGHTLIGHT), ensuring high levels of acceptability to maximise study retention.
      METHODS: A three-stage approach was employed: Stage 1 involved developing a
      conceptual framework, conducting literature/Internet searches and establishing
      content validity of the survey; Stage 2 confirmed the acceptability of methods of
      administration and consisted of four focus groups involving 11 young people (14
      25 years), three parents and two siblings; and Stage 3 established survey
      comprehension through telephone-administered cognitive interviews with a
      convenience sample of 23 young people aged 14-24 years. RESULT: Stage 1: Two
      hundred and thirty eight questions were developed from qualitative reports of
      young people's cancer and treatment-related experience. Stage 2: The focus groups
      identified three core themes: (i) issues directly affecting young people, e.g.
      impact of treatment-related fatigue on ability to complete survey; (ii) issues
      relevant to the actual survey, e.g. ability to answer questions anonymously;
      (iii) administration issues, e.g. confusing format in some supporting documents.
      Stage 3: Cognitive interviews indicated high levels of comprehension requiring
      minor survey amendments. CONCLUSION: Collaborating with young people with cancer
      has enabled a survey of to be developed that is both meaningful to young people
      but also examines patient experience and outcomes associated with specialist
      cancer care. Engagement of young people throughout the survey development has
      ensured the content appropriately reflects their experience and is easily
      understood. The BRIGHTLIGHT survey was developed for a specific research project
      but has the potential to be used as a TYA cancer survey to assess patient
      experience and the care they receive.

PMID- 26216213
TI  - Treatment of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: An
      International Task Force Consensus Statement.

PMID- 26216215
TI  - Alcohol use in the military: associations with health and wellbeing.
AB  - BACKGROUND: This study assessed the extent to which alcohol consumption in a
      military group differed from the general population, and how alcohol affected the
      military group's health and social functioning. METHODS: A cross sectional survey
      of military personnel (n = 5311) collected self-reported data on alcohol use
      (AUDIT scale) and general health, role limitations because of physical health
      problems (role physical), and social functioning scores (SF36 subscales).
      Logistic regression was used to compare drinking behaviours between the military
      sample and a general population sample, using the categories risky drinkers (>2
      units per day), low risk drinkers (<=2 standard drinks per day) and abstainers.
      Groups in the military sample with the highest levels of alcohol misuse (harmful
      drinking AUDIT >= 16, alcohol dependence AUDIT >= 20, and binge drinking) were
      also identified. Linear regression models were then used to assess the
      association between alcohol misuse and SF36 scores. RESULTS: There were fewer
      risky drinkers in the military sample than in the general population sample.
      There were also fewer abstainers, but more people who drank at a lower risk level
      (<=2 standard drinks per day), than in a sample of the general population.
      Harmful drinking and alcohol dependence were most commonly observed in men,
      younger age groups, non-commissioned officers and lower ranks as well as reserve
      and ex-serving groups. Alcohol misuse was clearly associated with poorer general
      health scores, more role limitations because of physical health problems, and
      lower social functioning. CONCLUSIONS: Although risky drinking was lower in the
      military group than in the general population, drinking was associated with
      poorer health, more limitations because of physical health problems, and poorer
      social functioning in Defence members. These results highlight the potential
      benefits for Defence forces in reducing alcohol use among members, in both those
      groups identified at highest risk, and across the military workforce as a whole.

PMID- 26216216
TI  - Epigenetic inheritance and the missing heritability.
AB  - Genome-wide association studies of complex physiological traits and diseases
      consistently found that associated genetic factors, such as allelic polymorphisms
      or DNA mutations, only explained a minority of the expected heritable fraction.
      This discrepancy is known as "missing heritability", and its underlying factors
      and molecular mechanisms are not established. Epigenetic programs may account for
      a significant fraction of the "missing heritability." Epigenetic modifications,
      such as DNA methylation and chromatin assembly states, reflect the high
      plasticity of the genome and contribute to stably alter gene expression without
      modifying genomic DNA sequences. Consistent components of complex traits, such as
      those linked to human stature/height, fertility, and food metabolism or to
      hereditary defects, have been shown to respond to environmental or nutritional
      condition and to be epigenetically inherited. The knowledge acquired from
      epigenetic genome reprogramming during development, stem cell differentiation/de
      differentiation, and model organisms is today shedding light on the mechanisms of
      (a) mitotic inheritance of epigenetic traits from cell to cell, (b) meiotic
      epigenetic inheritance from generation to generation, and (c) true
      transgenerational inheritance. Such mechanisms have been shown to include
      incomplete erasure of DNA methylation, parental effects, transmission of distinct
      RNA types (mRNA, non-coding RNA, miRNA, siRNA, piRNA), and persistence of subsets
      of histone marks. 

PMID- 26216217
TI  - Environmental contamination with Toxocara eggs: a quantitative approach to
      estimate the relative contributions of dogs, cats and foxes, and to assess the
      efficacy of advised interventions in dogs.
AB  - BACKGROUND: Environmental contamination with Toxocara eggs is considered the main
      source of human toxocariasis. The contribution of different groups of hosts to
      this contamination is largely unknown. Current deworming advices focus mainly on
      dogs. However, controversy exists about blind deworming regimens for >6-month-old
      dogs, as most of them do not actually shed Toxocara eggs. We aim to estimate the
      contribution of different non-juvenile hosts to the environmental Toxocara egg
      contamination and to assess the effects of different Toxocara-reducing
      interventions for dogs. METHODS: A stochastic model was developed to quantify the
      relative contribution to the environmental contamination with Toxocara eggs of
      household dogs, household cats, stray cats, and foxes, all older than 6 months in
      areas with varying urbanization degrees. The model was built upon an existing
      model developed by Morgan et al. (2013). We used both original and published data
      on host density, prevalence and intensity of infection, coprophagic behaviour,
      faeces disposal by owners, and cats' outdoor access. Scenario analyses were
      performed to assess the expected reduction in dogs' egg output according to
      different deworming regimens and faeces clean-up compliances. Estimates referred
      to the Netherlands, a country free of stray dogs. RESULTS: Household dogs
      accounted for 39% of the overall egg output of >6-month-old hosts in the
      Netherlands, followed by stray cats (27%), household cats (19%), and foxes (15%).
      In urban areas, egg output was dominated by stray cats (81%). Intervention
      scenarios revealed that only with a high compliance (90%) to the four times a
      year deworming advice, dogs' contribution would drop from 39 to 28%.
      Alternatively, when 50% of owners would always remove their dogs' faeces, dogs'
      contribution would drop to 20%. CONCLUSION: Among final hosts of Toxocara older
      than 6 months, dogs are the main contributors to the environmental egg
      contamination, though cats in total (i.e. both owned and stray) transcend this
      contribution. A higher than expected compliance to deworming advice is necessary
      to reduce dogs' egg output meaningfully. Actions focusing solely on household
      dogs and cats are unlikely to sufficiently reduce environmental contamination
      with eggs, as stray cats and foxes are also important contributors.

PMID- 26216218
TI  - Feasibility of a new method using two-dimensional transesophageal
      echocardiography for aortic annular sizing in patients undergoing transcatheter
      aortic valve implantation; a case-control study.
AB  - BACKGROUND: Accurate preoperative assessment of the aortic annulus dimension is
      crucial for successful transcatheter aortic valve implantation (TAVI). In this
      study we validated a new method using two-dimensional transesophageal
      echocardiography (2D-TEE) for measurement of the aortic annulus prior to TAVI.
      METHODS: We analysed 124 patients who underwent successful TAVI using a self
      expandable prosthesis, divided equally into two groups; in the study group we
      used the cross sectional short axis 2D-TEE for measurement of the aortic annulus
      and in the control group we used the long axis 2D-TEE. RESULTS: Both groups were
      comparable regarding the clinical parameters. On the other hand, patients in the
      study group had less left ventricular ejection fraction (38.9 % versus 45.6 %, p
      = 0.01). The aortic valve annulus was, although not statistically significant,
      smaller in the study group (21.58 versus 23.28 mm, p = 0.25). Post procedural
      quantification of the aortic regurgitation revealed that only one patient in both
      groups had severe aortic regurgitation (AR), in this patient the valve was
      implanted deep. The incidence of significant AR was higher in the control group
      (29.0 % versus 12.9 %, p = 0.027). CONCLUSIONS: Sizing of the aortic valve
      annulus using cross-sectional 2D-TEE offers a safe and plausible method for
      patients undergoing TAVI using the self-expandable prosthesis and is
      significantly superior to using long axis 2D-TEE.

PMID- 26216219
TI  - A molecular propeller effect for chiral separation and analysis.
AB  - Enantiomers share nearly identical physical properties but have different chiral
      geometries, making their identification and separation difficult. Here we show
      that when exposed to a rotating electric field, the left- and right-handed chiral
      molecules rotate with the field and act as microscopic propellers; moreover,
      owing to their opposite handedness, they propel along the axis of field rotation
      in opposite directions. We introduce a new molecular parameter called
      hydrodynamic chirality to characterize the coupling of rotational motion of a
      chiral molecule into its translational motion and quantify the direction and
      velocity of such motion. We demonstrate >80% enrichment level of counterpart
      enantiomers in solution without using chiral selectors or circularly polarized
      light. We expect our results to have an impact on multiple applications in drug
      discovery, analytical and chiral chemistry, including determination of absolute
      configuration, as well as in influencing the understanding of artificial and
      natural molecular systems where rotational motion of the molecules is involved. 

PMID- 26216220
TI  - Prevalence of asthma in Saudi adults: findings from a national household survey,
      2013.
AB  - BACKGROUND: There are not enough data on the epidemiology of asthma in the
      Kingdom of Saudi Arabia (KSA). We analyzed data from a national household survey
      conducted in KSA in 2013 to estimate prevalence, associated risk factors and
      control measurements of asthma. METHODS: The Saudi Health Interview Survey was a
      cross-sectional national multistage survey of 10,735 individuals aged 15 years or
      older. The survey included a detailed household questionnaire and a physical
      exam. We used self-reported clinical diagnosis of asthma to assess prevalence of
      asthma. RESULTS: The prevalence of asthma in KSA was 4.05 % (95 % confidence
      interval [CI]: 3.54-4.62 %). Asthma was less frequent in individuals with higher
      education but higher in former smokers and obese individuals. Around 76.7 % of
      asthma patients (95 % CI: 70.6-82.0 %) experienced an asthmatic attack, and 61.6
      % (95 % CI: 54.4-68.4 %) visited a hospital/emergency room because of asthma
      during the past year. Asthma attack was less frequent in older patients (odds
      ratio [OR] = 0.78, 95 %CI: 0.59-0.96 for each decade of life). Current use of
      medication for asthma was highly associated with asthma attacks (OR = 9.14, 95 %
      CI: 3.29-25.38). Asthma attack was also more frequent in individuals who were
      exposed to secondhand smoking (OR = 2.17, 95 %CI: 1.05-4.45) and those who were
      obese (OR = 3.01, 95 %CI: 1.34-6.78). CONCLUSION: Saudi Arabia has a relatively
      low prevalence of diagnosed asthma; however, many of the patients with known
      asthma do not have it under good control. Our study calls for programs to inform
      patients about the importance and proper means of controlling their condition.
      Implementing and monitoring of clinical guidelines can also help to improve
      asthma control among patients as well as identify undiagnosed cases.

PMID- 26216221
TI  - Quality of life in patients treated with first-line antiretroviral therapy
      containing nevirapine or efavirenz in Uganda: a prospective non-randomized study.
AB  - BACKGROUND: The goal of antiretroviral therapy (ART) is to suppress viral
      replication, reduce morbidity and mortality, and improve quality of life (QoL).
      For resource-limited settings, the World Health Organization recommends a first
      line regimen of two-nucleoside reverse-transcriptase inhibitors and one non
      nucleoside transcriptase inhibitor (nevirapine (NVP) or efavirenz (EFV)). There
      are few data comparing the QoL impact of NVP versus EFV. This study assessed the
      change in QoL and factors associated with QoL among HIV patients receiving ART
      regimens based on EFV or NVP. METHODS: We enrolled 640 people with HIV eligible
      for ART who received regimens including either NVP or EFV. QoL was assessed at
      baseline, three months and six months using Physical Health Summary (PHS) and
      Mental Health Summary (MHS) scores and the Global Person Generated Index (GPGI).
      Data were analyzed using generalized estimating equations, with ART regimen as
      the primary exposure, to identify associations between patient and disease
      factors and QoL. RESULTS: QoL increased on ART. The mean QoL scores did not
      differ significantly for regimens based on NVP versus EFV during follow-up for
      MHS and GPGI regardless of CD4 stratum and for PHS among patients with a CD4
      count >250 cells/MUL. The PHS-adjusted beta coefficients for ART regimens based
      on EFV versus NVP by CD4 count strata were as follows: -1.61 (95% CI -2.74, 
      0.49) for CD4 count <100 cells/MUL; 0.82 (0.22, 1.43) for CD4 count 101-250
      cells/MUL; and -1.33 (-5.66, 3.00) for CD4 count >250 cells/MUL. The
      corresponding MHS-adjusted beta coefficients were as follows: -0.39 (-1.40, 0.62)
      for CD4 < 100 cells/MUL; 0.16 (-0.66, 0.98) for CD4 count 101-250 cells/MUL; and 
      0.75 (-2.01, 0.51) for CD4 count >250 cells/MUL. The GPGI-adjusted odds ratios
      for EFV versus NVP were 0.51 (0.25, 1.04) for CD4 count <100 cells/MUL, 0.98
      (0.60, 1.58) for CD4 count 101-250 cells/MUL, 1.39 (0.66, 2.90) for CD4 > 250
      cells/MUL. QoL improved among patients on EFV over the 6-month follow-up period
      (MHS p < 0.001; PHS p = 0.04, p = 0.028). Overall, patients with depression (PHS
      p < 0.001; GPGI p < 0.001) had lower scores and women had lower MHS (on NVP, p =
      0.001). Other factors associated with lower QoL included alcohol use, low
      education level and advanced HIV disease. CONCLUSIONS: ART improves QoL. The
      results support use of either NVP or EFV. Patients initiating ART should be
      assessed for depression and managed appropriately. Women may require extra
      support to improve their QoL.

PMID- 26216222
TI  - Comparison of radii sets, entropy, QM methods, and sampling on MM-PBSA, MM-GBSA,
      and QM/MM-GBSA ligand binding energies of F. tularensis enoyl-ACP reductase
      (FabI).
AB  - To validate a method for predicting the binding affinities of FabI inhibitors,
      three implicit solvent methods, MM-PBSA, MM-GBSA, and QM/MM-GBSA were carefully
      compared using 16 benzimidazole inhibitors in complex with Francisella tularensis
      FabI. The data suggests that the prediction results are sensitive to radii sets,
      GB methods, QM Hamiltonians, sampling protocols, and simulation length, if only
      one simulation trajectory is used for each ligand. In this case, QM/MM-GBSA using
      6 ns MD simulation trajectories together with GB(neck2) , PM3, and the mbondi2
      radii set, generate the closest agreement with experimental values (r(2)  =
      0.88). However, if the three implicit solvent methods are averaged from six 1 ns
      MD simulations for each ligand (called "multiple independent sampling"), the
      prediction results are relatively insensitive to all the tested parameters.
      Moreover, MM/GBSA together with GB(HCT) and mbondi, using 600 frames extracted
      evenly from six 0.25 ns MD simulations, can also provide accurate prediction to
      experimental values (r(2)  = 0.84). Therefore, the multiple independent sampling
      method can be more efficient than a single, long simulation method. Since future
      scaffold expansions may significantly change the benzimidazole's physiochemical
      properties (charges, etc.) and possibly binding modes, which may affect the
      sensitivities of various parameters, the relatively insensitive "multiple
      independent sampling method" may avoid the need of an entirely new validation
      study. Moreover, due to large fluctuating entropy values, (QM/)MM-P(G)BSA were
      limited to inhibitors' relative affinity prediction, but not the absolute
      affinity. The developed protocol will support an ongoing benzimidazole lead
      optimization program.

PMID- 26216223
TI  - Molecular dynamic analysis of mutant Y195I alpha-cyclodextrin glycosyltransferase
      with switched product specificity from alpha-cyclodextrin to gamma-cyclodextrin.
AB  - Alpha-cyclodextrin (alpha-CD) glycosyltransferase (alpha-CGTase) can convert
      starch into alpha-CD blended with various proportions of beta-cyclodextrin (beta
      CD) and/or gamma-cyclodextrin (gamma-CD). In this study, we verified the
      catalytic characteristics of purified Y195I alpha-CGTase and elucidated the
      mechanism of action with molecular dynamic (MD) simulations. We found that
      purified Y195I alpha-CGTase produced less alpha-CD, slightly more beta-CD, and
      significantly more gamma-CD than wild-type alpha-CGTase. Correspondingly, alpha
      CD-based K m values increased, and beta-CD- and gamma-CD-based K m values
      decreased. MD simulation studies revealed that the dynamic trajectories of the
      substrate oligosaccharide chain in the mutant CGTase binding site were
      significantly different from those in the wild-type enzyme, with reduced
      hydrophobic interaction, finally resulting in different product specificity and
      more gamma-CD formation. 

PMID- 26216224
TI  - pi-Hole interaction: a theoretical insight into the mechanism of SO2 captured by
      [Et 2NEMim][Tetz] ionic liquids.
AB  - The mechanism of SO2 capture by 1-(2-diethylaminoethyl)-3-methylimidazolium
      tetrazolate ([Et2NEMim][Tetz]) was investigated using B3LYP hybrid density
      functional methods at 6-31 + G(d,p) level. In order to find the origin of the
      high capacity of the subjected ionic liquids (IL) for SO2 capture, the 1: n (n =
      1-5) complexes formed between [Et2NEMim][Tetz] and 1-5 SO2 molecules were
      optimized. Two interaction modes (pi-hole interaction and hydrogen bond) were
      found in each 1: n (n = 1-5) complex; the second order perturbation stabilization
      energies, E(2)s, confirmed that the main interaction mode was a pi-hole
      interaction. The calculated interaction energies indicated that the first SO2
      absorption should be chemical absorption. The capture of the second and third SO2
      should fall between chemical and physical interaction, and the fourth and fifth
      SO2 are incorporated by physical absorption. Thermodynamic analyses indicated
      that SO2 capture favors lower temperature and higher pressure. Owing to the
      interactions between SO2 and the [Tetz] anion or the [Et2NEMim] cation, the SOO
      asymmetric stretching frequency exhibits an obviously red shift in the complex.
      The strong absorptions of SOO asymmetric stretching in complex (1:5) appear at
      1295 cm(-1) (interaction between SO2 and the [Tetz](-) anion) and 1247 cm(-1)
      (interaction between SO2 and the tertiary nitrogen on the cation). Graphical
      Abstract Geometric structures of the most stable [ET 2 NEMim][Tetz]ionic liquid
      (IL; left), and most stable SO2 complex (n = 1-5; right) optimized at the B3LYP/6
      31+G (d,p) level (distances in angstroms).

PMID- 26216225
TI  - Superalkali atoms bonding to the phenalenyl radical: structures, intermolecular
      interaction and nonlinear optical properties.
AB  - Due to unpaired electrons, both radicals and superalkali are investigated widely.
      In this work, two interesting complexes (Li3O-PLY and Li3-PLY) were constructed
      by phenalenyl radical and superalkali atoms. Why are they interesting? Firstly,
      for Li3O-PLY and Li3-PLY, although the charge transfer between superalkali atoms
      and PLY is similar, the sandwich-like charge distribution for Li3O-PLY causes a
      smaller dipole moment than that of Li3-PLY. Secondly, their UV-vis absorption
      show that the maximum wavelengths for Li3O-PLY and Li3-PLY display a bathochromic
      shift compared to PLY. Moreover, Li3-PLY has two new peaks at 482 and 633 nm.
      Significantly, the beta 0 values of Li3-PLY (4943-5691 a.u.) are much larger than
      that of Li3O-PLY (225-347 a.u.). Further, the beta HRS values of Li3O-PLY
      decrease slightly while beta HRS of Li3-PLY increase dramatically with increasing
      frequency. It is our expectation that these results might provide beneficial
      information for theoretical and experimental studies on complexes with
      superalkali and PLY radicals. Graphical Abstract Two interesting complexes (Li3O
      PLY and Li3-PLY) were constructed by phenalenyl radical and superalkali atoms. We
      explore their structures, Wiberg bond indices, interaction energies and the
      static first hyperpolarizabilities (beta 0). The beta 0 values of Li3-PLY (4943
      5691 a.u.) were much larger than those of Li3O-PLY (225-347 a.u.).

PMID- 26216226
TI  - Disparities in osteoporosis treatments.
AB  - Osteoporosis treatment rates within 2 years following an index event (fragility
      fracture, osteoporotic bone mineral density (BMD) T-score, or osteoporosis ICD-9
      codes) were determined from 2005 to 2011. Most patients were not treated.
      Fracture patients had the lowest treatment rate. Low treatment rates also
      occurred in patients that were male, black, or had non-commercial insurance.
      INTRODUCTION: Clinical recognition of osteoporosis (osteoporotic BMD, assignment
      of an ICD-9 code, or the occurrence of fragility fractures) provides
      opportunities to treat patients at risk for future fracture. METHODS: A cohort of
      36,965 patients was identified from 2005 to 2011 in the Indiana Health
      Information Exchange, with index events after age 50 of either non-traumatic
      fractures, an osteoporosis ICD-9 code, or a BMD T-score <= -2.5. Patients with
      osteoporosis treatment in the preceding year were excluded. Medication records
      during the ensuing 2 years were extracted to identify osteoporosis treatments,
      demographics, comorbidities, and co-medications. Predictors of treatment were
      evaluated in a multivariable logistic regression model. RESULTS: The cohort was
      78 % female, 11 % black, 91 % urban-dwelling, and 53 % commercially insured. The
      index events were as follows: osteoporosis diagnosis (47 % of patients),
      fragility fracture (44 %), and osteoporotic T-scores (9 %). Within 2 years after
      the index event, 23.3 % received osteoporosis medications (of which, 82.2 % were
      oral bisphosphonates). Treatment rates were higher after osteoporosis diagnosis
      codes (29.3 %) or osteoporotic T-score (53.9 %) than after fracture index events
      (10.5 %) (p < 0.001). Age had an inverted U-shaped effect for women with highest
      odds around 60-65 years. Women (OR 1.86) and non-black patients (OR 1.52) were
      more likely to be treated (p < 0.001). Patients with public (versus commercial)
      insurance (OR 0.86, p < 0.001) or chronic comorbidities (ORs about 0.7-0.9, p <
      0.001) were less likely to be treated. CONCLUSION: Most osteoporosis treatment
      candidates remained untreated. Men, black patients, and patients with fracture or
      chronic comorbidities were less likely to receive treatment, representing
      disparity in the recognition and treatment of osteoporosis.

PMID- 26216227
TI  - Oxidized Low Density Lipoprotein Among the Elderly in Qinghai-Tibet Plateau.
AB  - OBJECTIVE: Several environmental factors including hypoxia have been reported to
      contribute to oxidative stress in individuals living in the highlands. However,
      little is known about the role of oxidized low-density lipoprotein (ox-LDL) among
      community-dwelling elderly in the Qinghai-Tibet plateau. METHODS: The study
      population comprised 168 community-dwelling elderly subjects aged 60 years or
      older (male to female ratio, 70:98; mean age, 65.8 years) living in Haiyan
      County, located 3000 to 3200 m above sea level, 30 km northwest of Xining,
      Qinghai. The subjects were volunteers who joined a Comprehensive Geriatric
      Assessment. Plasma ox-LDL was measured in 168 community-dwelling elderly subjects
      aged 60 years or older (23 Tibetans and 145 Hans) with a monoclonal antibody
      based enzyme-linked immunosorbent assay. RESULTS: Mean ox-LDL level was higher
      among Tibetan elderly than Han elderly (Tibetan, 79.0 +/- 29.6 U/L; Han, 62.8 +/-
      23.5 U/L; P = .003). Tibetan ethnicity was significantly associated with ox-LDL
      levels after adjusting for LDL cholesterol levels. In addition, high ox-LDL
      levels (>=70 U/L) were significantly associated with a homeostasis model
      assessment insulin resistance index of at least 1.6 (odds ratio [OR], 2.82; 95%
      confidence interval [95% CI], 1.11 to 7.15; P = .029) and ankle brachial pressure
      index of less than 1.0 (OR, 4.85; 95% CI, 1.14 to 10.00; P = .028), after
      adjusting for age, sex, and ethnicity. CONCLUSIONS: Our findings support the
      hypothesis that ox-LDL levels are higher among Tibetan elderly highlanders
      compared with those among Han elderly. As ox-LDL levels can affect insulin
      resistance and arteriosclerosis, further research is needed to determine how
      oxidative stress influences the health situation among elderly individuals at
      high altitudes.

PMID- 26216228
TI  - Multiple Irrigation and Debridements for Periprosthetic Joint Infections: Facing
      a Necessity or Just Prolonging the Inevitable?
AB  - Irrigation and debridement (I&D) may be a viable option in selected cases of
      periprosthetic joint infections (PJI). Our aim was to investigate the role of
      multiple I&Ds. Among 141 patients with PJI treated with I&D in our institution,
      19 were subjected to additional procedures. Their clinical characteristics were
      retrospectively reviewed and compared to the remaining patients treated with a
      single I&D. The probability of treatment failure (removal of implants) was not
      significantly different among the two groups. The interval between serial I&Ds
      was a significant factor determining outcomes. Patients treated with multiple
      I&Ds had a significantly higher prevalence of peripheral vascular disease. The
      decision to proceed with repeat of I&D should be made with caution. 

PMID- 26216229
TI  - A Novel Method for Assessment of Polyethylene Liner Wear in Radiopaque Tantalum
      Acetabular Cups: Clinical Validation in Patients Enrolled in a Randomized
      Controlled Trial.
AB  - Conventional radiostereometric analysis (RSA) for wear is not possible in
      patients with tantalum cups. We propose a novel method for wear analysis in
      tantalum cups. Wear was assessed by gold standard RSA and the novel method in
      total hip arthroplasty patients enrolled in a randomized controlled trial
      receiving either titanium or tantalum cups (n=46). The novel method estimated the
      center of the head using a model based on identification of two proximal markers
      on the stem and knowledge of the stem/head configuration. The novel method was
      able to demonstrate a pattern of wear that was similar to the gold standard in
      titanium cups. The novel method offered accurate assessment and is a viable
      solution for assessment of wear in studies with tantalum cups. 

PMID- 26216232
TI  - The role of LIFG-based executive control in sentence comprehension.
AB  - Prior research has shown that patients with damage to the left inferior frontal
      gyrus (LIFG) can have difficulties in executive control as well as understanding
      syntactic garden-paths, that is, sentences with a temporary syntactic ambiguity
      that resolve towards a less preferred interpretation. The present study tested
      two LIFG patients on object/subject garden path and matched syntactically
      unambiguous sentences. Besides syntactic ambiguity, support for the preferred but
      ultimately inappropriate interpretation was manipulated via verb bias, using
      verbs that were neutral between alternative analyses and verbs that were biased
      towards the context-inappropriate option. The LIFG patients, a non-LIFG patient,
      and healthy controls were tested on a sentence interpretation task (Experiment 1)
      and grammaticality judgement (Experiment 2). In contrast to the non-LIFG patient
      and controls, the LIFG patients showed impaired thematic role assignment across
      garden-path as well as unambiguous sentences, which tended to be worse with
      biased verbs. The results argue for a role of executive control in overcoming
      verb bias across diverse sentence processing situations, including, but not
      limited to, garden-path revision. 

PMID- 26216230
TI  - The CUPIC algorithm: an accurate model for the prediction of sustained viral
      response under telaprevir or boceprevir triple therapy in cirrhotic patients.
AB  - Triple therapy using boceprevir or telaprevir remains the reference treatment for
      genotype 1 chronic hepatitis C in countries where new interferon-free regimens
      have not yet become available. Antiviral treatment is highly required in
      cirrhotic patients, but they represent a difficult-to-treat population. We aimed
      to develop a simple algorithm for the prediction of sustained viral response
      (SVR) in cirrhotic patients treated with triple therapy. A total of 484 cirrhotic
      patients from the ANRS CO20 CUPIC cohort treated with triple therapy were
      randomly distributed into derivation and validation sets. A total of 52.1% of
      patients achieved SVR. In the derivation set, a D0 score for the prediction of
      SVR before treatment initiation included the following independent predictors
      collected at day 0: prior treatment response, gamma-GT, platelets, telaprevir
      treatment, viral load. To refine the prediction at the early phase of the
      treatment, a W4 score included as additional parameter the viral load collected
      at week 4. The D0 and W4 scores were combined in the CUPIC algorithm defining
      three subgroups: 'no treatment initiation or early stop at week 4',
      'undetermined' and 'SVR highly probable'. In the validation set, the rates of SVR
      in these three subgroups were, respectively, 11.1%, 50.0% and 82.2% (P < 0.001).
      By replacing the variable 'prior treatment response' with 'IL28B genotype',
      another algorithm was derived for treatment-naive patients with similar results.
      The CUPIC algorithm is an easy-to-use tool that helps physicians weigh their
      decision between immediately treating cirrhotic patients using
      boceprevir/telaprevir triple therapy or waiting for new drugs to become available
      in their country. 

PMID- 26216233
TI  - Hook plate fixation for acute acromioclavicular dislocations without
      coracoclavicular ligament reconstruction: a functional outcome study in military
      personnel.
AB  - The aim of our study was to evaluate the shoulder function after clavicular hook
      plate fixation of acute acromioclavicular dislocations (Rockwood type III) in a
      population group consisting exclusively of high-demand military personnel. This
      prospective study was carried out at a tertiary care military orthopaedic centre
      during 2012-2013 using clavicular hook plate for management of acromioclavicular
      injuries without coracoclavicular ligament reconstruction in 33 patients. All
      patients underwent routine implant removal after 16 weeks. The functional outcome
      was assessed at 3, 6 and 12 months after hook plate removal and 2 years from the
      initial surgery using the Constant Murley and UCLA Scores. All the patients were
      male serving soldiers and had sustained acromioclavicular joint dislocation
      (Rockwood type III). Mean age of the patient group was 34.24 years (21-55 years).
      The mean follow-up period in this study was 23.5 months (20-26 months) after hook
      plate fixation and an average of 19.9 months (17-22 months) after hook plate
      removal. The average Constant Score at 3 months after hook plate removal was 60.3
      as compared to 83.7 and 90.3 at 6 months and 1 year, respectively, and an average
      of 91.8 at the last follow-up that was approximately 2 years after initial
      surgery which was statistically significant (p value <0.05). The UCLA Score was
      an average of 15.27, 25.9 and 30.1 at 3, 6 months and 1 year, respectively, after
      removal of hook plate which improved further an average of 32.3 at the last
      follow-up, which was also statistically significant (p value <0.05). Clavicular
      hook plate fixation without coracoclavicular ligament reconstruction is a good
      option for acute acromioclavicular dislocations producing excellent medium-term
      functional results in high-demand soldiers. 

PMID- 26216234
TI  - DaPeCa-3: promising results of sentinel node biopsy combined with (18) F
      fluorodeoxyglucose positron emission tomography/computed tomography in clinically
      lymph node-negative patients with penile cancer - a national study from Denmark.
AB  - OBJECTIVES: To estimate the diagnostic accuracy of sentinel node biopsy (SNB)
      combined with preoperative (18) F-fluorodeoxyglucose positron emission
      tomography/computed tomography (FDG PET/CT) for inguinal lymph node (LN)
      evaluation in patients with invasive penile squamous cell carcinoma (PSCC) with
      no clinical evidence of inguinal metastases (cN0) at two tertiary centres with
      complete clinical follow-up. PATIENTS AND METHODS: From April 2010 in Centre one
      and from January 2013 in Centre two, we prospectively enrolled patients diagnosed
      with invasive PSCC and scheduled for SNB at the only two university centres
      treating penile cancer in Denmark. All patients had FDG PET/CT before SNB. The
      sentinel LNs were preoperatively located by planar lymphoscintigraphy in 134
      groins (68 patients) and by single-photon emission CT/CT in 120 groins (61
      patients). The primary endpoints were the sensitivity, specificity, and false
      negative rate of SNB combined with FDG PET/CT. The secondary endpoint was SNB
      related morbidity. RESULTS: We examined 254 groins in 129 patients by SNB
      combined with FDG PET/CT. The median (interquartile range, IQR) follow-up of
      survivors was 23 (14-35) months. Of 201 LN-negative groins, two were false
      negatives, and despite radio-chemotherapy treatment, both patients died from
      penile cancer. Four of 23 radiotracer-silent groins, had a FDG PET/CT-positive
      LNs and were surgically explored. In one of four of the explored groins, a
      positive LN was found. Combined FDG PET/CT-SNB sensitivity was 94.4% (95%
      confidence interval [CI] 81-99%) per groin. The false-negative rate was 5.6% (95%
      CI 1-19%) per groin. In 15 patients (11.6%) there were 25 SNB-related
      complications of Clavien-Dindo grades I-IIIa. The only Clavien-Dindo IIIa
      complication was an inguinal lymphocele treated by aspiration. CONCLUSION: In
      this study, we present a favourable SNB false-negative rate of 5.6% in a national
      cohort of clinically LN-negative patients with invasive PSCC with a pre-SNB FDG
      PET/CT scan. The combination of FDG PET/CT and SNB seems to be a promising
      diagnostic approach. Even so, a false-negative SNB was fatal in two of two cases
      and we are determined to continue the development of our SNB technique. The SNB
      related morbidity was limited.

PMID- 26216231
TI  - Endocannabinoid Signaling in Autism.
AB  - Autism spectrum disorder (ASD) is a complex behavioral condition with onset
      during early childhood and a lifelong course in the vast majority of cases. To
      date, no behavioral, genetic, brain imaging, or electrophysiological test can
      specifically validate a clinical diagnosis of ASD. However, these medical
      procedures are often implemented in order to screen for syndromic forms of the
      disorder (i.e., autism comorbid with known medical conditions). In the last 25
      years a good deal of information has been accumulated on the main components of
      the "endocannabinoid (eCB) system", a rather complex ensemble of lipid signals
      ("endocannabinoids"), their target receptors, purported transporters, and
      metabolic enzymes. It has been clearly documented that eCB signaling plays a key
      role in many human health and disease conditions of the central nervous system,
      thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for
      the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders.
      Here we present a modern view of the eCB system, and alterations of its main
      components in human patients and animal models relevant to ASD. This review will
      thus provide a critical perspective necessary to explore the potential
      exploitation of distinct elements of eCB system as targets of innovative
      therapeutics against ASD.

PMID- 26216235
TI  - The Impact of Twin Birth on Early Neonatal Outcomes.
AB  - OBJECTIVE: This study aims to describe the impact of twin birth, chorionicity,
      intertwin birth weight (BW) discordance and birth order on neonatal outcomes.
      STUDY DESIGN: We performed a hospital-based retrospective study on 2,170 twins
      (6.4% of all live births) and 2,217 singletons inborn 2007 to 2011. Data on
      neonatal characteristics, morbidities, and mortality were collected and compared.
      Univariate and multiple (adjusted for gestational age [GA] and gender) linear
      random intercept regression models were used. RESULTS: Overall, 62.3% of twins
      were born premature. At multiple regression, twins were similar to singletons for
      neonatal morbidities, but they were more likely to have lower BW and to be born
      by cesarean delivery. Monochorionic twins had lower GA and BW compared with
      dichorionic ones and were more likely to develop respiratory distress syndrome
      (odds ratio [OR], 1.7), hypoglycemia (OR, 3.3), need for transfusion, (OR, 3.4)
      but not brain abnormalities. Moderate and severe BW discordance were associated
      with longer length of stay and increased risk for morbidities but not for death.
      Birth order had no effects. CONCLUSION: Prematurity was the most common outcome
      in twins and accounted for the apparently increased risk in morbidities.
      Monochorionicity was confirmed as risk factor for lower GA and neonatal
      morbidities. BW discordance may play a role in developing neonatal complications
      and needs to be further investigated.

PMID- 26216236
TI  - A chromatographic objective function to characterise chromatograms with unknown
      compounds or without standards available.
AB  - Getting useful chemical information from samples containing many compounds is
      still a challenge to analysts in liquid chromatography. The highest complexity
      corresponds to samples for which there is no prior knowledge about their chemical
      composition. Computer-based methodologies are currently considered as the most
      efficient tools to optimise the chromatographic resolution, and further finding
      the optimal separation conditions. However, most chromatographic objective
      functions (COFs) described in the literature to measure the resolution are based
      on mathematical models fitted with the information obtained from standards, and
      cannot be applied to samples with unknown compounds. In this work, a new COF
      based on the automatic measurement of the protruding part of the chromatographic
      peaks (or peak prominences) that indicates the number of perceptible peaks and
      global resolution, without the need of standards, is developed. The proposed COF
      was found satisfactory with regard to the peak purity criterion when applied to
      artificial peaks and simulated chromatograms of mixtures built using the
      information of standards. The approach was applied to mixtures of drugs
      containing unknown impurities and degradation products and to extracts of
      medicinal herbs, eluted with acetonitrile-water mixtures using isocratic and
      gradient elution. 

PMID- 26216237
TI  - Effect of gradient steepness on the kinetic performance limits and peak
      compression for reversed-phase gradient separations of small molecules.
AB  - The effect of gradient steepness on the kinetic performance limits and peak
      compression effects has been assessed in gradient mode for the separation of
      phenol derivatives using columns packed with 2.6MUm core-shell particles. The
      effect of mobile-phase velocity on peak capacity was measured on a column with
      fixed length while maintaining the retention factor at the moment of elution and
      the peak-compression factor constant. Next, the performance limits were
      determined at the maximum system pressure of 100MPa while varying the gradient
      steepness. For the separation of small molecules applying a linear gradient with
      a broad span, the best performance limits in terms of peak capacity and analysis
      time were obtained applying a gradient-time-to-column-dead-time (tG/t0) ratio of
      12. The magnitude of the peak-compression factor was assessed by comparing the
      isocratic performance with that in gradient mode applying different gradient
      times. Therefore, the retention factors for different analytes were determined in
      gradient mode and the mobile-phase composition in isocratic mode was tuned such
      that the difference in retention factor was smaller than 2%. Peak-compression
      factors were quantitatively determined between 0.95 and 0.65 depending on
      gradient steepness and the gradient retention factor. 

PMID- 26216238
TI  - Role of Adenohypophysotropic Neurohormones in Endocrine Paraadenohypophysial
      Regulation of Peripheral Target Organs in Rat Ontogeny.
AB  - We tested the hypothesis that brain-derived chemical stimuli contribute to direct
      endocrine regulation of peripheral organs during ontogeny before blood-brain
      barrier closure. Dopamine and gonadotropin-releasing hormone present in high
      concentration in peripheral blood only before blood-brain barrier closure were
      chosen as the chemical stimuli. It was shown than dopamine in concentrations
      equal to its level in the peripheral blood inhibits prolactin secretion in
      organotypic culture of the pituitary gland from newborn rats via specific
      receptors. Experiments on organotypic culture of neonatal rat testicles showed
      that gonadotropin-releasing hormone stimulates testosterone secretion via
      specific receptors. We proved that chemical stimuli entering common circulation
      from the brain before blood-brain barrier closure could exert direct endocrine
      effect on peripheral organs. 

PMID- 26216239
TI  - Prenyltransferases as key enzymes in primary and secondary metabolism.
AB  - Attachment of isoprene units to various acceptors by prenylation plays an
      important role in primary and secondary metabolism of living organisms. Protein
      prenylation belongs to posttranslational modification and is involved in cellular
      regulation process. Prenylated secondary metabolites usually demonstrate
      promising biological and pharmacological activities. Prenyl transfer reactions
      catalyzed by prenyltransferases represent the key steps in the biosynthesis and
      contribute significantly to the structural and biological diversity of these
      compounds. In the last decade, remarkable progress has been achieved in the
      biochemical, molecular, and structural biological investigations of
      prenyltransferases, especially on those of the members of the
      dimethylallyltryptophan synthase (DMATS) superfamily. Until now, more than 40 of
      such soluble enzymes are identified and characterized biochemically. They
      catalyze usually regioselective and stereoselective prenylations of a series of
      aromatic substances including tryptophan, tryptophan-containing peptides, and
      other indole derivatives as well as tyrosine or even nitrogen-free substrates.
      Crystal structures of a number of prenyltransferases have been solved in the past
      10 years and provide a solid basis for understanding the mechanism of prenyl
      transfer reactions. 

PMID- 26216240
TI  - The biodegradation vs. biotransformation of fluorosubstituted aromatics.
AB  - Fluoroaromatics are widely and--in recent years--increasingly used as
      agrochemicals, starting materials for chemical syntheses and especially
      pharmaceuticals. This originates from the special properties the carbon-fluorine
      bond is imposing on organic molecules. Hence, fluoro-substituted compounds more
      and more are considered to be important potential environmental contaminants. On
      the other hand, the microbial potentials for their transformation and
      mineralization have received less attention in comparison to other haloaromatics.
      Due to the high electronegativity of the fluorine atom, its small size, and the
      extraordinary strength of the C-F bond, enzymes and mechanisms known to
      facilitate the degradation of chloro- or bromoarenes are not necessarily equally
      active with fluoroaromatics. Here, we review the literature on the microbial
      degradation of ring and side-chain fluorinated aromatic compounds under aerobic
      and anaerobic conditions, with particular emphasis being placed on the mechanisms
      of defluorination reactions.

PMID- 26216241
TI  - Degradation of 13C-labeled pyrene in soil-compost mixtures and fertilized soil.
AB  - Polycyclic aromatic hydrocarbons (PAH) are toxic pollutants widely distributed in
      the environment due to natural and anthropogenic processes. In order to mitigate
      tar oil contaminations with PAH, research on improving bioremediation approaches,
      which are sometimes inefficient, is needed. However, the knowledge on the fate of
      PAH-derived carbon and the microbial degraders in particular in compost
      supplemented soils is still limited. Here we show the PAH carbon turnover mass
      balance in microcosms with soil-compost mixtures or in farmyard fertilized soil
      using [(13)C6]-pyrene as a model PAH. Complete pyrene degradation of 100 mg/kg of
      soil was observed in all supplemented microcosms within 3 to 5 months, and the
      residual (13)C was mainly found as carbon converted to microbial biomass. Long
      term fertilization of soil with farmyard manure resulted in pyrene removal
      efficiency similar to compost addition, although with a much longer lag phase,
      higher mineralization, and lower carbon incorporation into the biomass. Organic
      amendments either as long-term manure fertilization or as compost amendment thus
      play a key role in increasing the PAH-degrading potential of the soil microbial
      community. Phospholipid fatty acid stable isotope probing (PLFA-SIP) was used to
      trace the carbon within the microbial population and the amount of biomass formed
      from pyrene degradation. The results demonstrate that complex microbial degrader
      consortia rather than the expected single key players are responsible for PAH
      degradation in organic-amended soil.

PMID- 26216242
TI  - Dominance of rumen microorganisms during cheese whey acidification: acidogenesis
      can be governed by a rare Selenomonas lacticifex-type fermentation.
AB  - The microbial basis of acidification process during spontaneous cheese whey
      wastewater fermentation was decrypted by implementing both culture-dependent and
      culture-independent techniques. Lac tobacillus and Bifidobacterium were the
      predominant taxa among the microbiota growing on MRS (deMan, Rogosa, and Sharpe),
      while Kazachstania unispora and Dekkera anomala yeast species were also isolated.
      Almost all Lactobacillus isolates were heterofermentative that could ferment
      glucose and lactose, with most of them being related to Lactobacillus hilgardii
      (99.0-100 % similarity). By employing fluorescence techniques, the dominance of
      long crescent-shaped bacteria in the acidogenic sludge was observed. Temperature
      gradient gel electrophoresis (TGGE), clone library, and next-generation
      sequencing techniques revealed the dominance of Selenomonas lacticifex. Based on
      Illumina data, Selenomonas in the continuous stirred-tank reactor (CSTR)
      represented 70.13 +/- 4.64 % of the bacterial reads, while other Veillonellaceae
      taxa (Megasphaera and Pectinatus) represented a notable proportion (6.54 %).
      Prevotella was only detected by Illumina sequencing as an important constituent
      of the microbial population (14.97 +/- 1.71 %). Budding yeasts represented 97 %
      of the fungal population in the CSTR, with Yarrowia strains representing 88.85 +/
      5.52 % of the fungal reads. Spontaneous cheese whey acidification can favor the
      dominance of rumen bacteria and here was driven by the rarely reported S.
      lacticifex-type fermentation, which should be taken into consideration during
      evaluation of acidogenesis in process simulation and modelling. Moreover, the
      important nervonic acid content detected indicates that acidogenic sludge can be
      used as a source for the production of high value-added biomedical substrates.

PMID- 26216243
TI  - Indirect Abuse Involving Children During the Separation Process.
AB  - Separation is believed to be an antidote to risk abusers pose to their partners
      and children and underlines many interventions in family, juvenile, and criminal
      court proceedings. Countering this belief is the claim that many abusers respond
      to the felt loss of power and control occasioned by separation by changing or
      escalating abusive tactics. This study complements research on post-separation by
      asking whether separation is associated with an increase in threats of indirect
      abuse, which relies on third parties to manipulate the victim. Children, and
      threats made against them, can be used as a proxy to control or intimidate the
      victim. Using data from the Chicago Women Health Risk Study ( N = 339), the
      current study examined whether mothers who were separated were at greater risk of
      abuse through threats against the children when compared with mothers who were
      still in a relationship with their abuser. Results indicated that separated
      mothers were four times more likely to report threats to take and threats to harm
      the children, Exp(B) = 4.05, p < .05; Exp(B) = 3.93, p < .05, than non-separated
      mothers. Findings can be used to inform child custody procedures and the design
      of Family Justice Centers.

PMID- 26216244
TI  - Mucosal tolerance of the hookworm Ancylostoma caninum in the gut of naturally
      infected wild dogs.
AB  - Ancylostoma caninum is a very pathogenic hookworm that locates in the small
      intestine of the dog and other canid species. The mucosal response of wild dogs
      naturally infected with A. caninum was investigated in this study. In spite of
      diffuse infiltrations of the mucosa with CD3+ , CD4+ , CD8+ , CD11c+ , CD21+ or
      MHC class II antigen cells, no focal infiltrations with any of these cell
      phenotypes were observed around the buccal capsule or the body of the feeding
      worms. Very few or no apoptotic cells could be detected around the worms fixed
      into the mucosa but they were detected on the tip of villi and in the superficial
      layer of cellular debris and proteinaceous exudate that covers the mucosa.
      Muc5AC, a mucine associated with expulsion of gut worms (Trichuris muris) was
      expressed extremely weakly or was not expressed at all in the intestine of the
      wild dogs infected with A. caninum. Our data show that individual specimens of A.
      caninum can reside for some time in the mucosa of the gut of dogs undetected and
      most likely unaffected by the effectors of the local immune response.

PMID- 26216245
TI  - Focal metatarsal fistulae syndrome affecting a greyhound dog successfully treated
      with topical 0.1% tacrolimus ointment.
AB  - Metatarsal fistulation is an uncommon cutaneous condition reported almost
      exclusively in German shepherd dogs and their cross-breeds. To the best of the
      authors' knowledge this is the first reported case of focal metatarsal fistulae
      syndrome affecting a greyhound. Remission was obtained within 6 weeks of
      commencing treatment using compounded 0.1% tacrolimus ointment twice daily and
      the dog remained stable for another 6 months with twice weekly application before
      treatment was discontinued. The dog remained in remission at the time of writing,
      which is 1 year after treatment withdrawal.

PMID- 26216246
TI  - Engineering microbial cell factories: Metabolic engineering of Corynebacterium
      glutamicum with a focus on non-natural products.
AB  - Corynebacterium glutamicum is the workhorse of biotechnological amino acid
      production. For more than 50 years amino acid producing strains of this
      actinomycete have been improved by classical breeding, metabolic engineering and
      systems and synthetic biology approaches. This review focusses mainly on recent
      developments on C. glutamicum strain development for non-natural products.
      Recently, metabolite sensors have accelerated classical strain breeding.
      Synthetic pathways for access to alternative carbon sources, such as pentoses,
      and to new products, such as alpha, omega-amino acids, alpha, omega-diamines,
      alpha-keto acids, isobutanol, carotenoids and terpenes, have been embedded in the
      central metabolism of C. glutamicum. Furthermore, C. glutamicum is a chassis for
      new and improved production processes that has been improved in two ways: by
      rendering it biotin prototrophic and by curing it from its prophage DNA followed
      by further genome reduction. The first combinations of this chassis approach with
      production will be highlighted. Although their transfer to industrial scale
      processes will have to be evaluated, these recent achievements indicate how
      synthetic biology helps realizing proof-of-principles. Moreover, current and
      future synthetic biology technology developments hold the promise to explore the
      full potential of C. glutamicum as production host for value-added chemicals. 

PMID- 26216247
TI  - Addendum to 'Quantifying the impact of transporters on cellular drug
      permeability'.

PMID- 26216248
TI  - Testosterone prescribing in the population-a short social epidemiological
      analysis in Sweden.
AB  - PURPOSE: In recent years, there has been an increased interest for use of
      pharmaceutical testosterone among elderly men. However, it is still scarcely
      studied if this use is conditioned by socioeconomic factors in the general
      population of elderly men. METHODS: Using individual-level data from a population
      based cohort of men aged 65-84 years in the County Scania, Sweden, we analysed
      testosterone use in 2006 in relation to demographic and socioeconomic factors by
      means of multiple logistic regression. We also analysed national data at the
      ecological level to investigate trends in prescribing between 2006 and 2014.
      RESULTS: The prevalence of testosterone use in Sweden among 65- to 84-year-old
      men increased by 83%, from 3.3 per 1000 men in 2006 to 6.0 in 2014. Testosterone
      use was more than twice as common in men in the highest income quintile compared
      with those in the lowest (0.68% versus 0.25%, odds ratio 2.69 and 95% confidence
      interval 1.80-4.02). Besides in the high-income group, testosterone use was
      highest in 65- to 69-year-old men, divorced men and, specially, in men with a
      previous hospital diagnose of hypogonadism. CONCLUSIONS: Our findings show
      socioeconomic inequities in prescription of testosterone. This is a short
      analysis based on limited data, but because information on this topic is scarce,
      our analysis adds a relevant piece of evidence and highlights the need for
      further research.

PMID- 26216249
TI  - Variation in Parasympathetic Dysregulation Moderates Short-term Memory Problems
      in Childhood Attention-Deficit/Hyperactivity Disorder.
AB  - Although attention deficit/hyperactivity disorder (ADHD) is associated with
      impairment in working memory and short-term memory, up to half of individual
      children with ADHD perform within a normative range. Heterogeneity in other ADHD
      related mechanisms, which may compensate for or combine with cognitive
      weaknesses, is a likely explanation. One candidate is the robustness of
      parasympathetic regulation (as indexed by respiratory sinus arrhythmia; RSA).
      Theory and data suggest that a common neural network is likely tied to both heart
      rate regulation and certain cognitive functions (including aspects of working and
      short-term memory). Cardiac-derived indices of parasympathetic reactivity were
      collected during short-term memory (STM) storage and rehearsal tasks from 243
      children (116 ADHD, 127 controls). ADHD was associated with lower STM
      performance, replicating previous work. In addition, RSA reactivity moderated the
      association between STM and ADHD - both as a category and a dimension -
      independent of comorbidity. Specifically, conditional effects revealed that high
      levels of withdrawal interacted with weakened STM but high levels of augmentation
      moderated a positive association predicting ADHD. Thus, variations in
      parasympathetic reactivity may help explain neuropsychological heterogeneity in
      ADHD.

PMID- 26216250
TI  - The effect of continuous interscalene brachial plexus block with 0.125%
      bupivacaine vs 0.2% ropivacaine on pain relief, diaphragmatic motility, and
      ventilatory function.
AB  - STUDY OBJECTIVE: Outpatient continuous interscalene brachial plexus blocks
      containing bupivacaine or ropivacaine are commonly used to control pain after
      shoulder surgery. Interscalene blocks cause hemidiaphragmatic paresis. Because
      ropivacaine preferentially blocks sensory fibers, it may cause less blockade of
      the phrenic nerve. The purpose of this study was to evaluate the effects of 2
      common continuous interscalene brachial plexus infusions: 0.125% bupivacaine vs
      0.2% ropivacaine. The study hypothesis is that respiratory function will be less
      attenuated using ropivacaine than bupivacaine without affecting pain relief.
      DESIGN: Study design was a prospective randomized double-blind study, registered
      (NCT 02059070), with institutional review board approval and written informed
      consent. SETTING: The setting was the preoperative and postoperative area in an
      orthopedic teaching hospital. PATIENTS: Outpatients scheduled for shoulder
      arthroscopic surgery were included. INTERVENTIONS: All patients underwent
      baseline measurements and interscalene catheter placement, then randomized to
      receive pumps containing either 0.2% ropivacaine or 0.125% bupivacaine.
      MEASUREMENTS: Study measurements included preoperative and postoperative bedside
      spirometry and ultrasonographic evaluations of diaphragmatic excursion,
      postoperative pain scores, and postdischarge oral opioid (oxycodone) consumption.
      MAIN RESULTS: There were no statistically significant differences between
      bupivacaine vs ropivacaine in outcomes of forced expiratory volume at 1 second
      change (-22% +/- 18.3% vs -29% +/- 14.9%), diaphragmatic excursion (-81.4% +/-
      37.95% vs -75.5% +/- 35.1%), VAS pain scores at rest (4.9 +/- 2.9 vs 3.5 +/-
      2.8), or oral opioid consumption (33.7 +/- 24.3 mg vs 35.1 +/- 33.9 mg).
      CONCLUSIONS: There was no difference in respiratory dysfunction or opioid
      requirements between interscalene continuous peripheral nerve blocks with 0.125%
      bupivacaine or 0.2% ropivacaine. Further study is required to identify anesthetic
      infusates that will control pain while decreasing the attenuation of pulmonary
      function.

PMID- 26216251
TI  - Design of Decorin-Based Peptides That Bind to Collagen I and their Potential as
      Adhesion Moieties in Biomaterials.
AB  - Mimicking the binding epitopes of protein-protein interactions by using small
      peptides is important for generating modular biomimetic systems. A strategy is
      described for the design of such bioactive peptides without accessible structural
      data for the targeted interaction, and the effect of incorporating such adhesion
      peptides in complex biomaterial systems is demonstrated. The highly repetitive
      structure of decorin was analyzed to identify peptides that are representative of
      the inner and outer surface, and it was shown that only peptides based on the
      inner surface of decorin bind to collagen. The peptide with the highest binding
      affinity for collagen I, LHERHLNNN, served to slow down the diffusion of a
      conjugated dye in a collagen gel, while its dimer could physically crosslink
      collagen, thereby enhancing the elastic modulus of the gel by one order of
      magnitude. These results show the potential of the identified peptides for the
      design of biomaterials for applications in regenerative medicine. 

PMID- 26216253
TI  - Statin allergy: Clinical experience and structural relation as a framework for
      evaluation.

PMID- 26216252
TI  - Symptom-Based Clustering in Chronic Rhinosinusitis Relates to History of Aspirin
      Sensitivity and Postsurgical Outcomes.
AB  - BACKGROUND: Symptoms burden in chronic rhinosinusitis (CRS) may be assessed by
      interviews or by means of validated tools such as the 22-item SinoNasal Outcome
      Test (SNOT-22). However, when only the total SNOT-22 scores are used, the pattern
      of symptom distribution and heterogeneity in patient symptoms is lost.
      OBJECTIVES: To use a standardized symptom assessment tool (SNOT-22) on
      preoperative symptoms to understand symptom heterogeneity in CRS and to aid in
      characterization of distinguishing clinical features between subgroups. METHODS:
      This was a retrospective review of 97 surgical patients with CRS. Symptom-based
      clusters were derived on the basis of presurgical SNOT-22 scores using
      unsupervised analysis and network graphs. Comparison between clusters was
      performed for clinical and demographic parameters, postsurgical symptom scores,
      and presence or absence of a history of aspirin sensitivity. RESULTS:
      Unsupervised analysis reveals coclustering of specific symptoms in the SNOT-22
      tool. Using symptom-based clustering, patients with CRS were stratified into
      severe overall (mean total score, 90.8), severe sinonasal (score, 62), moderate
      sinonasal (score, 40), moderate nonsinonasal (score, 37) and mild sinonasal
      (score, 16) clusters. The last 2 clusters were associated with lack of history of
      aspirin sensitivity. The first cluster had a rapid relapse in symptoms
      postoperatively, and the last cluster demonstrated minimal symptomatic
      improvement after surgery. CONCLUSION: Symptom-based clusters in CRS reveal a
      distinct grouping of symptom burden that may relate to aspirin sensitivity and
      treatment outcomes.

PMID- 26216254
TI  - The Effect of Viral Infection on Exhaled Nitric Oxide in Children with Acute
      Asthma Exacerbations.
AB  - BACKGROUND: Fraction of exhaled nitric oxide (Feno) level is used as an aid in
      the diagnosis and management of chronic asthma. Its role in acute asthma remains
      to be studied. OBJECTIVE: To determine whether Feno levels are elevated in
      children with asthma exacerbations compared with baseline, and whether there is a
      difference in Feno levels based on PCR positive (+) (respiratory virus isolated
      by PCR analysis) versus PCR negative (-) (respiratory virus not isolated by PCR
      analysis) status. METHODS: Children with a previous Feno level measurement while
      stable and who presented to an urgent care facility with an asthma exacerbation
      were enrolled. Feno levels, spirometry, and nasal swabs for viral PCR were
      obtained at the time of the exacerbation and following a course of prednisone.
      Data were available on 66 children. Linear mixed models were used to regress the
      outcomes of interest (FEV1, FEV1/forced vital capacity, forced expiratory flow at
      25% to 75% of forced vital capacity, and natural log Feno) on detected virus
      (yes/no), visit (baseline, exacerbation, follow-up), and the interaction between
      the detected virus and visit. RESULTS: Compared with baseline, higher Feno values
      and lower lung function were found at the time of an exacerbation. A respiratory
      virus was detected in 59% of the exacerbations. The interaction between PCR (+)
      and PCR (-) groups and visit on log Feno was marginally significant (P = .07).
      There was no difference in log Feno between the PCR (+) and PCR (-) groups at
      baseline, while higher log Feno was found in the PCR (-) group at the time of
      exacerbation and following prednisone (P = .05 and .001, respectively).
      CONCLUSIONS: Higher Feno concentration in PCR (-) exacerbations suggests an
      eosinophilic predominance in nonviral compared with viral exacerbations.

PMID- 26216255
TI  - High similarity between lentil and other lentil-like-proteins (dal) complicates
      recommendations on avoidance in lentil allergic patients.

PMID- 26216256
TI  - mHealth SMS text messaging interventions and to promote medication adherence: an
      integrative review.
AB  - AIMS AND OBJECTIVES: This article is an integrative review of the evidence for
      mobile health Short Message Service text messages as an innovative and emerging
      intervention to promote medication adherence. Authors completed this review to
      draw conclusions and implications towards establishing a scientific foundation
      for use of text messages to promote medication adherence, thus informing clinical
      practice. BACKGROUND: The World Health Organization has identified medication
      adherence as a priority global problem. Text messages are emerging as an
      effective means of improving health behaviours and in some diseases to promote
      medication adherence. However, a gap in the literature indicates lack of evidence
      in guiding theories and content of text messages, which should be synthesised
      prior to use in clinical practice. DESIGN: Integrative review. METHODS:
      Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica
      dataBASE, Scopus, the Cochrane Library and PubMed were searched for relevant
      studies between 2004-2014. Inclusion criteria were (1) implementation of a text
      message intervention and (2) medication adherence to a prescribed oral medication
      as a primary outcome. Articles were assessed for quality of methodology and
      measures of adherence. An integrative review process was used to perform
      analysis. RESULTS: Thirteen articles meeting the inclusion criteria are included
      in this review. Nine of 13 studies found adherence rates improved between 15.3
      17.8% when using text messages to promote medication adherence. Text messages
      that were standardised, tailored, one- or two-way and timed either daily to
      medication regimen, weekly or monthly showed improvement in medication adherence.
      CONCLUSIONS: This review established a scientific basis for text messages as an
      intervention to improve medication adherence across multiple diseases. Future
      large rigorous randomised trials are needed to further test text messaging
      interventions. RELEVANCE TO CLINICAL PRACTICE: This review provides clinicians
      with the state of the science with regard to text messaging interventions that
      promote medication adherence. A description of intervention components are
      provided to aid nurses in development of text messages and in translating
      evidence into practice.

PMID- 26216257
TI  - The incidence and outcome of allied disorders of Hirschsprung's disease in Japan:
      Results from a nationwide survey.
AB  - BACKGROUND: Allied disorders of Hirschsprung's disease (ADHD) have been proposed
      to be the concept of the functional obstruction of the intestine with the
      presence of ganglion cells in the terminal rectum. They are classified into two
      categories based on pathology: (1) abnormal ganglia, including immaturity of
      ganglia, hypoganglionosis (HG), and intestinal neuronal dysplasia; (2) normal
      ganglia, including megacystis microcolon intestinal hypoperistalsis syndrome
      (MMIHS), segmental dilatation (SD), internal anal sphincter achalasia (IASA), and
      chronic idiopathic intestinal pseudo-obstruction (CIIP). Some of these show poor
      prognosis, therefore, the establishment of criteria and appropriate treatment
      strategies is required. METHODS: The questionnaires were sent to the 161 major
      institutes of pediatric surgery or gastroenterology in Japan, in order to collect
      the cases of ADHD during 10 years from 2001 and 2010. RESULTS: In total, 355
      cases were collected. They included 28 immaturity of ganglia, 130 HG (121
      congenital, 9 acquired), 18 intestinal neuronal dysplasia, 33 MMIHS, 43 SD, three
      IASA, and 100 CIIP. Of the 95 institutes, 69 (72.6%) had their own criteria for
      ADHD. Criteria were based on clinical symptoms and signs, and conventional
      pathological examinations. Prognosis was poor in congenital HG, MMIHS, and CIIP,
      while the others showed good survival rates. CONCLUSION: Almost all Japanese
      cases of ADHD in the past 10 years were collected. Congenital HG and CIIP showed
      relatively high incidence, whereas acquired HG and IASA were extremely rare in
      Japan. The criteria of each disorder were also collected and summarized.
      Prognosis was poor in congenital HG, MMIHS, and CIIP.

PMID- 26216258
TI  - Development and evaluation of a new biodegradable vena cava filter in a canine
      model.
AB  - PURPOSE: Preliminary testing of a new biodegradable inferior vena cava filter in
      a canine model. METHODS: The biodegradable filter consisted of two parts, a
      filter cone and a stent. The filter cone was constructed of six polyglycolic acid
      polymer strands anchored to a handmade absorbable stent. Central inferior vena
      cava fixation was accomplished by the absorbable stent, which was made of
      polycaprolactone. Device insertion was performed through a 9F sheath under
      ultrasound guidance on 10 adult beagles. The filters were operatively retrieved
      at 6 weeks after implantation. The inferior venae cavae were subsequently
      analyzed grossly and using light microscopy. RESULTS: None of the 10 beagles had
      abnormal vital signs. All of the 10 filters migrated cephalad approximately <2 cm
      and remained below the renal vein ostia. One specimen had evidence of
      incorporated residual strands within the caval wall on gross examination. The
      caval wall became thickened at the level of filter placement without significant
      lumen narrowing. There was no evidence of pulmonary embolism caused by
      degradation products of the absorbable strands. CONCLUSION: Biodegradable
      inferior vena cava filters are feasible and potentially could be used in specific
      patients who are at temporary high risk of venous thromboembolism.

PMID- 26216259
TI  - Identifying risk factors for brain metastasis in breast cancer patients:
      Implication for a vigorous surveillance program.
AB  - OBJECTIVE: Brain metastasis occurs in 10-15% of metastatic breast cancer patients
      and is associated with poor prognosis. This study aims to identify tumor
      characteristics of primary breast cancer, which are related to brain metastases
      in Hong Kong Chinese patients. METHODS: A retrospective study of patients with
      invasive breast cancer receiving treatment in a university hospital from January
      2001 to December 2008 was performed. The clinicopathological factors of patients
      with brain metastases were analyzed and compared with those who had no brain
      metastasis. Risk factors for brain metastasis were identified by univariate
      analysis first and then by multivariate analysis. RESULTS: A total of 912
      patients with invasive breast cancer were treated during the study period. Of
      these, 30 patients were found to have distant metastases to brain. Patients with
      brain metastases had more breast tumors of higher histological grade (Grade III,
      78.9% vs. 30.2%; p = 0.001). Their tumors also had a significantly higher rate of
      negative estrogen receptors (78.9% vs. 30.2%, p = 0.001). On multivariate
      analysis, only high tumor grading was found to be predictive of developing brain
      metastasis. CONCLUSION: Chinese breast cancer patients with brain metastasis were
      more likely to have high-grade tumors and negative estrogen receptor status. A
      more vigorous surveillance program for the central nervous system should be
      considered for this group of patients.

PMID- 26216260
TI  - Evaluation of the modified HTK solution in pancreas transplantation-An
      experimental model.
AB  - INTRODUCTION: One of the great challenges in pancreas transplantation is the
      ischemia reperfusion injury. It is mentioned that free oxygen and/or nitrogen
      radicals play a prominent role in this phase. To minimize this problem, a
      modified histidine-tryptophan-ketoglutarate (HTK) solution that contains modified
      antioxidants has been developed. Our aim was to evaluate this solution in
      improving the viability of the pancreas in comparison with standard HTK and
      University of Wisconsin (UW) solutions in a porcine model of pancreas
      transplantation. MATERIALS AND METHODS: Twenty-three Landrace pigs were divided
      into three identical groups. After a 10-hour preservation time at 4 degrees C,
      the pancreas was implanted in the organs of the recipients in a standardized
      manner. Serum parameters were assessed prior to and after implantation on the
      1(st) postoperative day, 3(rd) postoperative day, and 7(th) postoperative day.
      Furthermore, three biopsies were taken: prior to and after reperfusion, and on
      Day 7 to assess the grafts. RESULTS: An analysis of serum glucose among the three
      groups showed no significant differences. Evaluation of the insulin levels showed
      no significant difference between the modified and standard HTK groups; however,
      differences between HTK and UW were significant (p = 0.004 in favor of UW
      solutions). The histopathological results showed a trend of a higher grade of
      rejection of pancreas tissue in the UW group compared to both HTK groups.
      CONCLUSION: The modified HTK solution could preserve the pancreas for the
      preservation of the graft with similar results to those observed for standard
      solutions without any significant difference. The trend showed that the
      pathological finding in the UW group was not as good as that in the modified HTK
      and standard HTK groups.

PMID- 26216262
TI  - Corrigendum.

PMID- 26216261
TI  - Effect of TNF-alpha blockade on coagulopathy and endothelial cell activation in
      xenoperfused porcine kidneys.
AB  - BACKGROUND: Following pig-to-primate kidney transplantation, endothelial cell
      activation and xenogenic activation of the recipient's coagulation eventually
      leading to organ dysfunction and microthrombosis can be observed. In this study,
      we examined the effect of a TNF-receptor fusion protein (TNF-RFP) on endothelial
      cell activation and coagulopathy utilizing an appropriate ex vivo perfusion
      system. METHODS: Using an ex vivo perfusion circuit based on C1-Inhibitor (C1
      Inh) and low-dose heparin administration, we have analyzed consumptive
      coagulopathy following contact of human blood with porcine endothelium. Porcine
      kidneys were recovered following in situ cold perfusion with Histidine-tryptophan
      ketoglutarate (HTK) organ preservation solution and were immediately connected to
      a perfusion circuit utilizing freshly drawn pooled porcine or human AB blood. The
      experiments were performed in three individual groups: autologous perfusion (n =
      5), xenogenic perfusion without any further pharmacological intervention (n =
      10), or with addition of TNF-RFP (n = 5). After perfusion, tissue samples were
      obtained for real-time PCR and immunohistological analyses. Endothelial cell
      activation was assessed by measuring the expression levels of E-selectin, ICAM-1,
      and VCAM-1. RESULTS: Kidney survival during organ perfusion with human blood, C1
      Inh, and heparin, but without any further pharmacological intervention was 126 +/
      78 min. Coagulopathy was observed with significantly elevated concentrations of
      D-dimer and thrombin-antithrombin complex (TAT), resulting in the formation of
      multiple microthrombi. Endothelial cell activation was pronounced, as shown by
      increased expression of E-selectin and VCAM-1. In contrast, pharmacological
      intervention with TNF-RFP prolonged organ survival to 240 +/- 0 min (max.
      perfusion time; no difference to autologous control). Formation of microthrombi
      was slightly reduced, although not significantly, if compared to the xenogenic
      control. D-dimer and TAT were elevated at similar levels to the xenogenic control
      experiments. In contrast, endothelial cell activation, as shown by real-time PCR,
      was significantly reduced in the TNF-RFP group. CONCLUSION: We conclude that
      although coagulopathy was not affected, TNF-RFP is able to suppress inflammation
      occurring after xenoperfusion in this ex vivo perfusion model.

PMID- 26216263
TI  - Modeling proteins as residue interaction networks.
AB  - Proteins are the ultimate carriers of information encoded within genes. The
      salient feature of proteins is their ability to perform a vast array of function
      with extraordinary specificity. This specificity of proteins is related directly
      to their structural conformations, which arises as a result of complex
      interactions among its constituent amino acid residues. Thus, analyzing proteins
      through these interactions collectively is an extremely important, interesting
      and effective way to understand their dynamical and structural properties. This
      review summarizes recent graph theoretical approaches in the field of amino acid
      residue interaction networks (RIN), [also known as residue interaction graphs
      (RIG), protein contact networks (PCN) or residue contact networks (RCN)] and the
      outcomes thereof. It explains the strengths of network formalism in unraveling
      various aspects of the complex phenomena, upon which the structure and function
      of proteins have a direct bearing. 

PMID- 26216264
TI  - In vitro synergistic effect of the CM11 antimicrobial peptide in combination with
      common antibiotics against clinical isolates of six species of multidrug
      resistant pathogenic bacteria.
AB  - During the last decades, increase of antibiotic resistance among pathogenic
      bacteria has been considered as a global concern. Therefore, it is important to
      find new antimicrobial agents and/or therapeutic strategies. In previous studies
      we investigated antibacterial activity of the CM11 peptide against multiple drug
      resistant clinical isolates of six bacteria species including Pseudomonas
      aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, Escherichia coli,
      Klebsiella pneumoniae and Salmonella typhimurium. In this study, in order to
      reduce treatment costs and the cytotoxic effect of CM11 peptide, was analyzed its
      synergic interaction with selected antibiotics. In this reason, specific
      antibiotics for each bacterium were selected considering the guidelines of the
      "Clinical and Laboratory Standards Institute". Based on the results , using a
      checkerboard procedure through the broth microdilution method, MICs of antibiotic
      agents alone and in combination with the peptide were determined. In most cases,
      synergistic effects between CM11 peptide and selected antibiotics against six
      bacteria species were observed as partial synergy. However, for S. aureus and P.
      aeruginosaa synergic interaction between peptide and selective antibiotics was
      observed with penicillin and ceftazidime, respectively. For K. pneumoniae,
      synergic effect was observed when CM11 peptide was used in combination with
      norfloxacin and also the combination of peptide with norfloxacin showed synergic
      effect against A. baumannii. Combination between the CM11 peptide and
      ciprofloxacin showed synergic effect on E. coli while only partial synergy was
      observed for S. typhimurium in combination with cefotaxime and ceftazidime. These
      results suggest that when selected antibiotic used in combination with the CM11
      peptide, the dose of some antibiotics, especially the dose independent
      antibiotics, may be reduced for eliminating drug resistant bacteria. 

PMID- 26216265
TI  - The Use of Affinity Tags to Overcome Obstacles in Recombinant Protein Expression
      and Purification.
AB  - Research and industrial demands for recombinant proteins continue to increase
      over time for their broad applications in structural and functional studies and
      as therapeutic agents. These applications often require large quantities of
      recombinant protein at desirable purity, which highlights the importance of
      developing and improving production approaches that provide high level expression
      and readily achievable purity of recombinant protein. E. coli is the most widely
      used host for the expression of a diverse range of proteins at low cost. However,
      there are common pitfalls that can severely limit the expression of exogenous
      proteins, such as stability, low solubility and toxicity to the host cell. To
      overcome these obstacles, one strategy that has found to be promising is the use
      of affinity tags or carrier peptide to aid in the folding of the target protein,
      increase solubility, lower toxicity and increase the level of expression. In the
      meantime, the tags and fusion proteins can be designed to facilitate affinity
      purification. Since the fusion protein may not exhibit the native conformation of
      the target protein, various strategies have been developed to remove the tag
      during or after purification to avoid potential complications in structural and
      functional studies and to obtain native biological activities. Despite extensive
      research and rapid development along these lines, there are unsolved problems and
      imperfect applications. This focused review compares and contrasts various
      strategies that employ affinity tags to improve bacterial expression and to
      facilitate purification of recombinant proteins. The pros and cons of the
      approaches are discussed for more effective applications and new directions of
      future improvement. 

PMID- 26216266
TI  - Efficient Purification of rhG-CSF and its PEGylated Forms and Evaluation for In
      Vitro Activities.
AB  - Granulocyte-colony stimulating factor (G-CSF) has commonly been used to help the
      patients to recover from neutropenia inflicted due to radiotherapy, organ
      transplants and chemotherapy. As the number of people undergoing these therapies
      and procedures are increasing world-wide, the need for more economical ways of G
      CSF production and improvement in its efficacy has become increasingly crucial.
      In the present study, recombinant human G-CSF (rhG-CSF) was expressed in E. coli
      and its purification process was optimized by demonstrating better efficiency and
      higher recoveries (upto 54%) in a multi-step chromatographic purification
      process, which is greater than the existing reports. Additionally, the efficacy
      of rhG-CSF was increased by derivatizing with polyethylene glycol (PEG; upto 85%
      PEGylation), which increases the plasma clearance time, reduces the
      immunogenicity and requires less frequent administration to the patient. Overall,
      the present study suggests a cost-effective purification process of rhG-CSF and
      also proposes its efficient conjugation with PEG for enhanced efficacy as
      compared to the existing commercially available forms. 

PMID- 26216267
TI  - Humanin Peptide Binds to Insulin-Like Growth Factor-Binding Protein 3 (IGFBP3)
      and Regulates Its Interaction with Importin-beta.
AB  - Nuclear translocation of IGFBP3 by importin-beta1 is a prerequisite for IGFBP3
      induced apoptosis. The neuroprotective peptide humanin (HN) counteracts IGFBP3
      induced cell death. However, the mechanism by which humanin protects cells is
      currently unknown. The natural synthesis of this peptide decreases with age,
      coincident with the likelihood for the development of Alzheimer's Disease, making
      it a promising target for therapeutics. We have examined the effect of full
      length humanin and a synthetic analogue (HN 3-19), known to be sufficient for its
      neuroprotective function, on the interaction between IGFBP3 and importin-beta1.
      Using competitive ligand dot blotting, co-immunoprecipitation, and an ELISA-based
      binding assay, we determined that 1) humanin binds to IGFBP3 with a Kd of 5.05 uM
      and 2) both humanin (IC50 of 18.1 uM) and HN 3-19 (IC50 of 10.3 MUM) interfere
      with the binding of importin-beta1 to IGFBP3 in vitro. We also demonstrated that
      HN 3-19 is able to reduce the rate of apoptosis in a human lung adenocarcinoma
      cell line, suggesting a possible mechanism of action for humanin as an inhibitor
      of IGFBP3 nuclear translocation. Understanding the exact mechanism by which
      humanin and its analogue, HN 3-19, bind to IGFPB3 and regulate its interaction
      with importin-beta1 will open the door to modulating the protein-protein
      interactions involved in neuronal cell death. 

PMID- 26216268
TI  - Organophosphorus Inhibition and Characterization of Recombinant Guinea Pig
      Acetylcholinesterase.
AB  - Organophosphorus (OP) pesticides and nerve agents have been designed to inhibit
      the hydrolysis of the neurotransmitter acetylcholine by covalently binding to the
      active site serine of acetylcholinesterase while Alzheimer drugs and
      prophylactics, such as tacrine, are characterized by reversible binding.
      Historically, the guinea pig has been believed to be the best non-primate model
      for OP toxicology and medical countermeasure development because, similarly to
      humans, guinea pigs have low amounts of circulating OP metabolizing
      carboxylesterase. To explore the hypothesis that guinea pigs are the appropriate
      responder species for OP toxicology and medical countermeasure development,
      guinea pig acetylcholinesterase (gpAChE) was cloned into pENTR/D-TOPO, recombined
      into pT-Rex-DEST30 and expressed in Human Embryonic Kidney 293 cells. Recombinant
      gpAChE was purified to a specific activity of 800 U/mg using size exclusion and
      immobilized nickel affinity chromatography, with purity confirmed by gel
      electrophoresis. Ellman's assay was used to enzymatically characterize gpAChE,
      identifying a K(M) of 154+/-18.7 umol L(-1) and a k(cat) of 4.79x10(4)+/
      5.26x10(2) /sec. Apparent gpAChE IC50's for diisopropylfluorophosphate,
      dicrotophos, paraoxon, and an Alzheimer's drug, tacrine, were found to be 10.1+/
      1.98, 337+/-108, 1.02+/-0.29 and 0.30+/-0.01 umol L(-1), respectively. Apparent
      gpAChE inhibition constants for diisopropylfluorophosphate, dicrotophos,
      paraoxon, and tacrine were found to be 8.40+/-0.60, 4.50+/-0.30, 0.29+/-0.01 and
      0.42+/-0.07 umol L(-1), respectively. Lineweaver-Burk plots confirmed tacrine as
      a mixed inhibitor and paraoxon, dicrotophos and diisopropylfluorophosphate as
      irreversible non-competitive inhibitors. gpAChE bimolecular rate constants for
      diisopropylfluorophosphate, dicrotophos and paraoxon were found to be 1.44+/
      0.33x10(4), 1.56+/-0.12x10(3) and 4.57+/- 0.23x10(5) L umol(-1) min(-1),
      respectively. Although the blood levels of OP metabolizing carboxylesterases in
      the guinea pig are similar to the low levels in human blood, the gpAChE is
      different in its enzymology. Therefore, medical countermeasures against OP
      intoxication should be tested for efficacy with the recombinant form of gpAChE
      prior to initiating animal studies.

PMID- 26216269
TI  - Time-resolved imaging of prompt-gamma rays for proton range verification using a
      knife-edge slit camera based on digital photon counters.
AB  - Proton range monitoring may facilitate online adaptive proton therapy and improve
      treatment outcomes. Imaging of proton-induced prompt gamma (PG) rays using a
      knife-edge slit collimator is currently under investigation as a potential tool
      for real-time proton range monitoring. A major challenge in collimated PG imaging
      is the suppression of neutron-induced background counts. In this work, we present
      an initial performance test of two knife-edge slit camera prototypes based on
      arrays of digital photon counters (DPCs). PG profiles emitted from a PMMA target
      upon irradiation with a 160 MeV proton pencil beams (about 6.5 * 10(9) protons
      delivered in total) were measured using detector modules equipped with four DPC
      arrays coupled to BGO or LYSO : Ce crystal matrices. The knife-edge slit
      collimator and detector module were placed at 15 cm and 30 cm from the beam axis,
      respectively, in all cases. The use of LYSO : Ce enabled time-of-flight (TOF)
      rejection of background events, by synchronizing the DPC readout electronics with
      the 106 MHz radiofrequency signal of the cyclotron. The signal-to-background
      (S/B) ratio of 1.6 obtained with a 1.5 ns TOF window and a 3 MeV-7 MeV energy
      window was about 3 times higher than that obtained with the same detector module
      without TOF discrimination and 2 times higher than the S/B ratio obtained with
      the BGO module. Even 1 mm shifts of the Bragg peak position translated into clear
      and consistent shifts of the PG profile if TOF discrimination was applied, for a
      total number of protons as low as about 6.5 * 10(8) and a detector surface of 6.6
      cm * 6.6 cm.

PMID- 26216270
TI  - Knowledge and attitude of health-care professionals in hospitals towards
      pharmacovigilance in Saudi Arabia.
AB  - BACKGROUND: Drug safety has major implications for patients' lives. However, this
      concept is still considered new to some healthcare professionals. OBJECTIVE: This
      study aims to investigate the knowledge and awareness of Saudi healthcare
      professionals to pharmacovigilance (PV). Setting Governmental and private
      hospitals at three main cities in Saudi Arabia (Riyadh, Jeddah, and Dammam).
      METHODS: A cross-sectional survey among healthcare professionals (pharmacists,
      physicians, and nurses) within 12 Saudi hospitals was conducted between November
      and December 2012. The questionnaire consisted of 18 questions assessing the
      knowledge, awareness, and attitude of healthcare professionals (HCPs) towards
      science and the concept of PV. Descriptive statistics were used to analyze the
      data. The data were analyzed using Statistical Analysis Software (SAS 9.3). Main
      outcome measure Knowledge, attitude and practice of HCPs toward
      pharmacovigilance. RESULTS: Three-hundred and thirty-two healthcare professionals
      completed the survey (response rate 72 %), 110 (34 %) physicians, 106 (33 %)
      pharmacists, and 104 (32 %) nurses. More than half of the participants (55 %) did
      not know the correct definition of PV. Two-thirds of the respondents, 207 (65.5
      %), had knowledge of the aim of post-marketing surveillance, yet only 113 (36.9
      %) were aware that the National Pharmacovigilance and Drug Safety Center is the
      official body for monitoring adverse drug reaction in Saudi Arabia. In addition,
      34.7 % agreed that lack of time could be a major barrier for reporting. The
      majority of the respondents (78.4 %) believed that reporting was a professional
      obligation and hospitals should have a drug safety department. CONCLUSIONS: There
      was a limited knowledge of pharmacovigilance that could have affected reporting
      incidence. Educational intervention and a practical training program need to be
      applied by the drug regulatory body as well as health authorities to enhance the
      pharmacovigilance and drug safety culture in Saudi Arabia.

PMID- 26216271
TI  - The tyrosine kinase inhibitor genistein induces the detachment of rotavirus
      particles from the cell surface.
AB  - Group A rotaviruses are a major cause of severe gastroenteritis in young infants.
      In this work we evaluated the potential role of protein tyrosine kinases on
      rotavirus infectivity and viral progeny production. From the broad-spectrum
      inhibitors tested, only genistein, a flavonoid, inhibited rotavirus infectivity.
      The inhibition observed was dose and strain dependent, with more than 10-fold
      IC50 differences for some rotavirus strains, and the effect of the drug was shown
      to be dependent of their activity as a protein tyrosine kinase inhibitor, since
      the inactive analogue of genistein, daidzein, had no effect on virus infection.
      Investigation of the stage of virus replication blocked by the drug showed that
      it interferes with the early interactions of the virus with receptors and/or co
      receptors, since treatment of the cells with genistein promoted the detachment of
      the virus from the cell surface. 

PMID- 26216272
TI  - Confocal Raman microscopy to monitor extracellular matrix during dental pulp stem
      cells differentiation.
AB  - Regenerative medicine brings promising applications for mesenchymal stem cells,
      such as dental pulp stem cells (DPSCs). Confocal Raman microscopy, a noninvasive
      technique, is used to study osteogenic differentiation of DPSCs. Integrated Raman
      intensities in the 2800 to 3000 cm-1 region (C-H stretching) and the 960  cm-1
      peak (nu1 PO43-) were collected (to image cells and phosphate, respectively), and
      the ratio of two peaks 1660 over 1690  cm-1 (amide I bands) to measure the
      collagen cross-linking has been calculated. Raman spectra of DPSCs after 21 days
      differentiation reveal several phosphate peaks: nu1 (first stretching mode) at
      960  cm-1, nu2 at 430  cm-1, and nu4 at 585  cm-1 and collagen cross-linking can
      also be calculated. Confocal Raman microscopy enables monitoring osteogenic
      differentiation in vitro and can be a credible tool for clinical stem cell based
      research.

PMID- 26216273
TI  - Editorial Comment on "Male-to-Female Genital Reassignment Surgery: A
      Retrospective Review of Surgical Technique and Complications in 60 Patients".

PMID- 26216274
TI  - MEG-measured auditory steady-state oscillations show high test-retest
      reliability: A sensor and source-space analysis.
AB  - Stability of oscillatory signatures across magnetoencephalography (MEG)
      measurements is an important prerequisite for basic and clinical research that
      has been insufficiently addressed. Here, we evaluated the test-retest reliability
      of auditory steady-state responses (ASSRs) over two MEG sessions. The study
      required participants (N=13) to detect the rare occurrence of pure tones
      interspersed within a stream of 5 Hz or 40 Hz amplitude-modulated (AM) tones.
      Intraclass correlations (ICC; Shrout and Fleiss, 1979) were derived to assess
      stability of spectral power changes and the inter-trial phase coherence (ITPC) of
      task-elicited neural responses. ASSRs source activity was estimated using eLORETA
      beamforming from bilateral auditory cortex. ASSRs to 40 Hz AM stimuli evoked
      stronger power modulation and phase-locking than 5 Hz stimulation. Overall,
      spectral power and ITPC values at both sensor- and source-level showed robust ICC
      values. Notably, ITPC measures yielded higher ICCs (~0.86-0.96) between sessions
      compared to the assessment of spectral power change (~0.61-0.82). Our data
      indicate that spectral modulations and phase consistency of ASSRs in MEG data are
      highly reproducible, providing support for MEG-measured oscillatory parameters in
      basic and clinical research.

PMID- 26216275
TI  - Preclinical evaluation of a promising C-11 labeled PET tracer for imaging
      phosphodiesterase 10A in the brain of living subject.
AB  - Phosphodiesterase 10A (PDE10A) plays a key role in the regulation of brain
      striatal signaling. A PET tracer for PDE10A may serve as a tool to evaluate
      PDE10A expression in vivo in central nervous system disorders with striatal
      pathology. Here, we further characterized the binding properties of a previously
      reported radioligand we developed for PDE10A, [(11)C]TZ1964B, in rodents and
      nonhuman primates (NHPs). The tritiated counterpart [(3)H]TZ1964B was used for in
      vitro binding characterizations in rat striatum homogenates and in vitro
      autoradiographic studies in rat brain slices. The carbon-11 labeled
      [(11)C]TZ1964B was utilized in the ex vivo autoradiography studies for the brain
      of rats and microPET imaging studies for the brain of NHPs. MicroPET scans of
      [(11)C]TZ1964B in NHPs were conducted at baseline, as well as with using a
      selective PDE10A inhibitor MP-10 for either pretreatment or displacement. The in
      vivo regional target occupancy (Occ) was obtained by pretreating with different
      doses of MP-10 (0.05-2.00 mg/kg). Both in vitro binding assays and in vitro
      autoradiographic studies revealed a nanomolar binding affinity of [(3)H]TZ1964B
      to the rat striatum. The striatal binding of [(3)H]TZ1964B and [(11)C]TZ1964B was
      either displaced or blocked by MP-10 in rats and NHPs. Autoradiography and
      microPET imaging confirmed that the specific binding of the radioligand was found
      in the striatum but not in the cerebellum. Blocking studies also confirmed the
      suitability of the cerebellum as an appropriate reference region. The binding
      potentials (BPND) of [(11)C]TZ1964B in the NHP striatum that were calculated
      using either the Logan reference model (LoganREF, 3.96 +/- 0.17) or the
      simplified reference tissue model (SRTM, 4.64 +/- 0.47), with the cerebellum as
      the reference region, was high and had good reproducibility. The occupancy
      studies indicated a MP-10 dose of 0.31 +/- 0.09 mg/kg (LoganREF)/0.45 +/-
      0.17mg/kg (SRTM) occupies 50% striatal PDE10A binding sites. Studies in rats and
      NHPs demonstrated radiolabeled TZ1964B has a high binding affinity and good
      specificity for PDE10A, as well as favorable in vivo pharmacokinetic properties
      and binding profiles. Our data suggests that [(11)C]TZ1964B is a promising
      radioligand for in vivo imaging PDE10A in the brain of living subject.

PMID- 26216276
TI  - Brains striving for coherence: Long-term cumulative plot formation in the default
      mode network.
AB  - Many everyday activities, such as engaging in conversation or listening to a
      story, require us to sustain attention over a prolonged period of time while
      integrating and synthesizing complex episodic content into a coherent mental
      model. Humans are remarkably capable of navigating and keeping track of all the
      parallel social activities of everyday life even when confronted with
      interruptions or changes in the environment. However, the underlying cognitive
      and neurocognitive mechanisms of such long-term integration and profiling of
      information remain a challenge to neuroscience. While brain activity is generally
      traceable within the short time frame of working memory (milliseconds to
      seconds), these integrative processes last for minutes, hours or even days. Here
      we report two experiments on story comprehension. Experiment I establishes a
      cognitive dissociation between our comprehension of plot and incidental facts in
      narratives: when episodic material allows for long-term integration in a coherent
      plot, we recall fewer factual details. However, when plot formation is
      challenged, we pay more attention to incidental facts. Experiment II investigates
      the neural underpinnings of plot formation. Results suggest a central role for
      the brain's default mode network related to comprehension of coherent narratives
      while incoherent episodes rather activate the frontoparietal control network.
      Moreover, an analysis of cortical activity as a function of the cumulative
      integration of narrative material into a coherent story reveals to linear
      modulations of right hemisphere posterior temporal and parietal regions. Together
      these findings point to key neural mechanisms involved in the fundamental human
      capacity for cumulative plot formation. 

PMID- 26216277
TI  - Age and sex related differences in subcortical brain iron concentrations among
      healthy adults.
AB  - Age and sex can influence brain iron levels. We studied the influence of these
      variables on deep gray matter magnetic susceptibilities. In 183 healthy
      volunteers (44.7 +/- 14.2 years, range 20-69, ? 49%), in vivo quantitative
      susceptibility mapping (QSM) at 1.5T was performed to estimate brain iron
      accumulation in the following regions of interest (ROIs): caudate nucleus (Cd),
      putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus
      (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the
      influence of age and sex on magnetic susceptibility by specifying a series of
      structural equation models. The distributions of susceptibility varied in degree
      across the structures, conforming to histologic findings (Hallgren and Sourander,
      1958), with the highest degree of susceptibility in the Gp and the lowest in the
      Th. Iron increase correlated across several ROIs, which may reflect an underlying
      age-related process. Advanced age was associated with a particularly strong
      linear rise of susceptibility in the striatum. Nonlinear age trends were found in
      the Rn, where they were the most pronounced, followed by the Pul and Sn, while
      minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex
      related variations were observed, so that women showed lower levels of
      susceptibility in the Sn after accounting for age. Regional susceptibility of the
      Pul increased linearly with age in men but exhibited a nonlinear association with
      age in women with a leveling off starting from midlife. Women expected to be post
      menopause (+51 years) showed lower total magnetic susceptibility in the
      subcortical gray matter. The current report not only is consistent with previous
      reports of age related variations of brain iron, but also adds to the current
      knowledge by reporting age-related changes in less studied, smaller subcortical
      nuclei. This is the first in-vivo report to show lower total subcortical brain
      iron levels selectively in women from midlife, compared to men and younger women.
      These results encourage further assessment of sex differences in brain iron. We
      anticipate that age and sex are important co-factors to take into account when
      establishing a baseline level for differentiating pathologic neurodegeneration
      from healthy aging. The variations in regional susceptibility reported herein
      should be evaluated further using a longitudinal study design to determine within
      person changes in aging.

PMID- 26216279
TI  - [15 years of minimally invasive paediatric cardiac surgery; development and
      trends].
AB  - INTRODUCTION: The minimally invasive approach is seldom reported in paediatric
      cardiac surgery. Teams gathering experience are scarce, with programs focused on
      simple cases. The experience is presented on a series of over 200 cases operated
      on in the past 15 years. MATERIAL AND METHODS: A sub-mammary approach program was
      started in 2000, which was gradually extended to include more complex and younger
      patients. The axillary incision was adopted in 2009, following the same steps. In
      2013, the mini-sternotomy incision was introduced, increasing our armamentarium.
      From July 2000 until December 2014, 203 patients were operated on. The sub
      mammary approach was used in 102 cases, axillary in 50 patients, mini-sternotomy
      in 44, postero-lateral thoracotomy in 4 cases, and upper mini-sternotomy in 3.
      RESULTS: By diagnosis, ostium secundum atrial septal defect was the most common
      (128), followed by sinus venosus (20), ventricular septal defect (20), ostium
      primum (16), and others (19). One patient was converted to sternotomy. No
      neurological events were detected. The mean age was 7.8/3.7 and 1.8 years, and
      the mean weight was 28.1/16.1 and 9.4 Kg. in the sub-mammary, axillary and mini
      sternotomy approaches, respectively. The aesthetic results were excellent.
      CONCLUSIONS: Based on our 15 years of experience, minimally invasive surgery is
      safe and yields excellent cosmetic results. The gradual introduction of
      alternative approaches (sub-mammary, axillary, mini-sternotomy) allowed us to set
      up guidelines and learning curves. The wide range of incisions enables the most
      appropriate one to be selected depending on age/weight and cardiac condition.

PMID- 26216280
TI  - [Neurally adjusted ventilatory assist increases respiratory variability and
      improves patient-ventilator synchronisation].

PMID- 26216278
TI  - A group ICA based framework for evaluating resting fMRI markers when disease
      categories are unclear: application to schizophrenia, bipolar, and
      schizoaffective disorders.
AB  - Schizophrenia (SZ), bipolar disorder (BP) and schizoaffective disorder (SAD)
      share some common symptoms, and there is still a debate about whether SAD is an
      independent category. To the best of our knowledge, no study has been done to
      differentiate these three disorders or to investigate the distinction of SAD as
      an independent category using fMRI data. This study is aimed to explore
      biomarkers from resting-state fMRI networks for differentiating these disorders
      and investigate the relationship among these disorders based on fMRI networks
      with an emphasis on SAD. Firstly, a novel group ICA method, group information
      guided independent component analysis (GIG-ICA), was applied to extract subject
      specific brain networks from fMRI data of 20 healthy controls (HC), 20 SZ
      patients, 20 BP patients, 20 patients suffering from SAD with manic episodes
      (SADM), and 13 patients suffering from SAD with depressive episodes exclusively
      (SADD). Then, five-level one-way analysis of covariance and multiclass support
      vector machine recursive feature elimination were employed to identify
      discriminative regions from the networks. Subsequently, the t-distributed
      stochastic neighbor embedding (t-SNE) projection and the hierarchical clustering
      were implemented to investigate the relationship among those groups. Finally, to
      evaluate the generalization ability, 16 new subjects were classified based on the
      found regions and the trained model using original 93 subjects. Results show that
      the discriminative regions mainly included frontal, parietal, precuneus,
      cingulate, supplementary motor, cerebellar, insula and supramarginal cortices,
      which performed well in distinguishing different groups. SADM and SADD were the
      most similar to each other, although SADD had greater similarity to SZ compared
      to other groups, which indicates that SAD may be an independent category. BP was
      closer to HC compared with other psychotic disorders. In summary, resting-state
      fMRI brain networks extracted via GIG-ICA provide a promising potential to
      differentiate SZ, BP, and SAD. 

PMID- 26216282
TI  - Atrial fibrillation coincides with the advanced glycation end product N(epsilon)
      (carboxymethyl)lysine in the atrium.
AB  - Presence of advanced glycation end products (AGEs) in the heart induces a
      proinflammatory phenotype. However, the presence of AGEs within atrial tissue of
      atrial fibrillation (AF) patients is unknown and was analyzed here. Left atrial
      appendage tissue from 33 AF patients and 9 controls was analyzed for the presence
      of the major AGEs N(epsilon)-(carboxymethyl)lysine (CML), VCAM-1, neutrophilic
      granulocytes, lymphocytes, and macrophages in both the fat tissue and myocardium
      separately. The total amount of fibrosis was also analyzed. Presence of CML was
      significantly higher in blood vessels of the left atrial appendage in AF patients
      as compared to controls, independent of diabetes mellitus. In AF patients, VCAM-1
      expression in blood vessels and the numbers of infiltrated neutrophilic
      granulocytes, lymphocytes, and macrophages significantly increased compared to
      controls, and were highest in the fat tissue; there was no significant difference
      in fibrosis compared to controls. Interestingly, total amount of CML and fibrosis
      in AF and control patients correlated positively. Finally, there was no
      difference between AF patients based on AF type or surgical indication in the
      presence of CML, VCAM-1 expression, inflammatory cells, and fibrosis. Our results
      indicate that in AF the intramyocardial blood vessels of the left atrial
      appendage have an increased CML presence and proinflammatory status coinciding
      with a local increase in the number of inflammatory cells. 

PMID- 26216283
TI  - Role of platelet-derived growth factor-CC in capillary rarefaction in renal
      fibrosis.
AB  - We have identified platelet-derived growth factor (PDGF)-CC as a potent
      profibrotic mediator in kidney fibrosis and pro-angiogenic mediator in glomeruli.
      Because renal fibrosis is associated with progressive capillary rarefaction, we
      asked whether PDGF-CC neutralization in fibrosis might have detrimental anti
      angiogenic effects leading to aggravated peritubular capillary loss. We analyzed
      capillary rarefaction in mice with and without PDGF-CC neutralization (using
      genetically deficient mice and neutralizing antibodies), in three different
      models of renal interstitial fibrosis, unilateral ureteral obstruction,
      unilateral ischemia-reperfusion, Col4a3-deficient (Alport) mice, and healthy
      animals. Independent of the effect of PDGF-CC neutralization on renal fibrosis,
      we found no difference in capillary rarefaction between PDGF-CC-neutralized mice
      and mice with intact PDGF-CC. We also found no differences in microvascular
      leakage (determined by extravasation of Evans Blue Dye) and in renal relative
      blood volume quantified using in vivo microcomputed tomography. PDGF-CC
      neutralization had no effects on renal microvasculature in healthy animals.
      Capillary endothelium did not express PDGF receptor-alpha, suggesting that
      potential PDGF-CC effects would have to be indirect. PDGF-CC neutralization or
      deficiency was not associated with preservation or accelerated loss of
      peritubular capillaries, suggesting no significant pro-angiogenic effects of PDGF
      CC during renal fibrosis. From a clinical perspective, the profibrotic effects of
      PDGF-CC outweigh the pro-angiogenic effects and, thus, do not limit a potential
      therapeutic use of PDGF-CC inhibition in renal fibrosis. 

PMID- 26216284
TI  - Inhibition of matrix metalloproteinase activity reverses corneal endothelial
      mesenchymal transition.
AB  - Ex vivo culture or regeneration of corneal endothelial cells often is subjected
      to gradual endothelial-mesenchymal transition and loss of function. Here, we
      found that during ex vivo culture, bovine corneal endothelial cells underwent
      endothelial-mesenchymal transition and had an up-regulated expression and
      activity of matrix metalloproteinases. Inhibition of matrix metalloproteinase
      activity in confluent bovine corneal endothelial cells decreased the level of
      endothelial-mesenchymal transition regulators: snail and slug. The
      phosphorylation and degradation of the key Wnt signaling pathway modulator active
      beta-catenin also were accelerated with the broad-spectrum matrix
      metalloproteinase inhibitor Marimastat, which may result from decreased N
      cadherin shedding and increased intact N-cadherin molecules on the cell membrane.
      Intracameral injection of Marimastat also suppressed basic fibroblast growth
      factor-induced endothelial-mesenchymal transition in a rat corneal endothelium
      cryo-injury model and significantly diminished the corneal edema. Our study
      indicated that inhibition of matrix metalloproteinase activity can reverse
      endothelial-mesenchymal transition and preserve the function of corneal
      endothelial cells both during ex vivo culture and in vivo. This may offer a
      potential therapeutic target in regenerative medicine for the treatment of
      corneal endothelial dysfunctions. 

PMID- 26216285
TI  - HNF4alpha regulates claudin-7 protein expression during intestinal epithelial
      differentiation.
AB  - The intestinal epithelium is a dynamic barrier that maintains the distinct
      environments of intestinal tissue and lumen. Epithelial barrier function is
      defined principally by tight junctions, which, in turn, depend on the regulated
      expression of claudin family proteins. Claudins are expressed differentially
      during intestinal epithelial cell (IEC) differentiation. However, regulatory
      mechanisms governing claudin expression during epithelial differentiation are
      incompletely understood. We investigated the molecular mechanisms regulating
      claudin-7 during IEC differentiation. Claudin-7 expression is increased as
      epithelial cells differentiate along the intestinal crypt-luminal axis. By using
      model IECs we observed increased claudin-7 mRNA and nascent heteronuclear RNA
      levels during differentiation. A screen for potential regulators of the CLDN7
      gene during IEC differentiation was performed using a transcription factor/DNA
      binding array, CLDN7 luciferase reporters, and in silico promoter analysis. We
      identified hepatocyte nuclear factor 4alpha as a regulatory factor that bound
      endogenous CLDN7 promoter in differentiating IECs and stimulated CLDN7 promoter
      activity. These findings support a role of hepatocyte nuclear factor 4alpha in
      controlling claudin-7 expression during IEC differentiation. 

PMID- 26216287
TI  - Pathogenesis of Lyme neuroborreliosis in an animal model of infection.

PMID- 26216286
TI  - Novel rat model for neurocysticercosis using Taenia solium.
AB  - Neurocysticercosis is caused by Taenia solium infecting the central nervous
      system and is the leading cause of acquired epilepsy and convulsive conditions
      worldwide. Research into the pathophysiology of the disease and appropriate
      treatment is hindered by lack of cost-effective and physiologically similar
      animal models. We generated a novel rat neurocysticercosis model using
      intracranial infection with activated T. solium oncospheres. Holtzman rats were
      infected in two separate groups: the first group was inoculated
      extraparenchymally and the second intraparenchymally, with different doses of
      activated oncospheres. The groups were evaluated at three different ages.
      Histologic examination of the tissue surrounding T. solium cysticerci was
      performed. Results indicate that generally infected rats developed cysticerci in
      the brain tissue after 4 months, and the cysticerci were observed in the
      parenchymal, ventricle, or submeningeal brain tissue. The route of infection did
      not have a statistically significant effect on the proportion of rats that
      developed cysticerci, and there was no dependence on infection dose. However, rat
      age was crucial to the success of the infection. Epilepsy was observed in 9% of
      rats with neurocysticercosis. In histologic examination, a layer of collagen
      tissue, inflammatory infiltrate cells, perivascular infiltrate, angiogenesis,
      spongy change, and mass effect were observed in the tissue surrounding the cysts.
      This study presents a suitable animal model for the study of human
      neurocysticercosis. 

PMID- 26216288
TI  - Note of concern.
AB  - This Note of Concern relates to Ezzat et al Am J Pathol 163:1177-1184. 

PMID- 26216289
TI  - A system for tumor heterogeneity evaluation and diagnosis based on tumor markers
      measured routinely in the laboratory.
AB  - OBJECTIVES: To develop an efficient and reliable approach to estimate tumor
      heterogeneity and improve tumor diagnosis using multiple tumor markers measured
      routinely in the clinical laboratory. METHODS: A total of 161 patients with
      different cancers were recruited as the cancer group, and 91 patients with non
      oncological conditions were required as the non-oncological disease group. The
      control group comprised 90 randomly selected healthy subjects. AFP, CEA, CYFRA,
      CA125, CA153, CA199, CA724, and NSE levels were measured in all these subjects
      with a chemiluminescent microparticle immunoassay. The tumor marker with the
      maximum S/CO value (sample test value:cutoff value for discriminating individuals
      with and without tumors) was considered as a specific tumor marker (STM) for an
      individual. Tumor heterogeneity index (THI)=N/P (N: number of STMs; P: percentage
      of individuals with STMs in a certain tumor population) was used to quantify
      tumor heterogeneity: high THI indicated high tumor heterogeneity. The tumor
      marker index (TMI), TMI = STM*(number of positive tumor markers+1), was used for
      diagnosis. RESULTS: The THIs of lung, gastric, and liver cancers were 8.33, 9.63,
      and 5.2, respectively, while the ROC-areas under the curve for TMI were 0.862,
      0.809, and 0.966. CONCLUSION: In this study, we developed a novel index for tumor
      heterogeneity based on the expression of various routinely evaluated serum tumor
      markers. Development of an evaluation system for tumor heterogeneity on the basis
      of this index could provide an effective diagnostic tool for some cancers.

PMID- 26216290
TI  - Environmentally Driven Migration in a Social Network Game.
AB  - Cooperative behaviors are common in humans, and they are the fundamental basis of
      our society. Theoretical and experimental studies have modeled environments where
      the behaviors of humans, or agents, have been restricted to analyze their social
      behavior. However, it is important that such studies can be generalized to a less
      restrictive environment in order to understand human society. Social network
      games (SNGs) provide a powerful tool for the quantitative study of human behavior
      using a less restrictive environment than in previous studies. We focused on
      multilevel selection, one of the theoretical frameworks used to study the
      evolution of cooperation. The evolution of cooperation by multilevel selection
      requires that the continual assortment between cooperators and noncooperators is
      generated; thus, humans may have acquired mechanisms that ensure assortment
      (e.g., migration between groups). This study aims to investigate this mechanism
      in a less restrictive environment. For this purpose, we researched the effect of
      migration based on data analysis in an SNG where the players could behave more
      freely than was possible in the environments used in the previous studies. We
      showed that players maintained assortment between cooperators and defectors in
      this SNG, where it appears that environmentally driven migration generated the
      assortment. 

PMID- 26216291
TI  - Proteomics Reveals a Role for Attachment in Monocyte Differentiation into
      Efficient Proinflammatory Macrophages.
AB  - Monocytes are blood-borne cells of the innate immune system. They can be
      differentiated and activated into proinflammatory macrophages that might be
      employed in tumor immune therapy. Monocyte exposure to lipopolysaccharide (LPS)
      is a standard method to induce a proinflammatory macrophage state, with the
      resultant population comprising both adherent and nonadherent cells. In the
      current study, we aimed to identify the differences in proteomes of these
      monocyte subpopulations, which addresses a more general question about the role
      of attachment in monocyte differentiation. Label-free proteomics of a model of
      human monocytes (THP-1 cell line) revealed that the cells remaining in suspension
      upon LPS treatment were activated by cytokines and primed for rapid
      responsiveness to pathogens. In terms of proteome change, the adhesion process
      was orthogonal to activation. Adherent cells exhibited signs of differentiation
      and enhanced innate immune responsivity, being closer to macrophages. These
      findings indicate that adherent, LPS-treated cells would be more appropriate for
      use in tumor therapeutic applications. 

PMID- 26216293
TI  - A priori model independent inverse potential mapping: the impact of electrode
      positioning.
AB  - INTRODUCTION: In inverse potential mapping, local epicardial potentials are
      computed from recorded body surface potentials (BSP). When BSP are recorded with
      only a limited number of electrodes, in general biophysical a priori models are
      applied to facilitate the inverse computation. This study investigated the
      possibility of deriving epicardial potential information using only 62 torso
      electrodes in the absence of an a priori model. METHODS: Computer simulations
      were used to determine the optimal in vivo positioning of 62 torso electrodes.
      Subsequently, three different electrode configurations, i.e., surrounding the
      thorax, concentrated precordial (30 mm inter-electrode distance) and super
      concentrated precordial (20 mm inter-electrode distance) were used to record BSP
      from three healthy volunteers. Magnetic resonance imaging (MRI) was performed to
      register the electrode positions with respect to the anatomy of the patient.
      Epicardial potentials were inversely computed from the recorded BSP. In order to
      determine the reconstruction quality, the super-concentrated electrode
      configuration was applied in four patients with an implanted MRI-conditional
      pacemaker system. The distance between the position of the ventricular lead tip
      on MRI and the inversely reconstructed pacing site was determined. RESULTS: The
      epicardial potential distribution reconstructed using the super-concentrated
      electrode configuration demonstrated the highest correlation (R = 0.98; p < 0.01)
      with the original epicardial source model. A mean localization error of 5.3 mm
      was found in the pacemaker patients. CONCLUSION: This study demonstrated the
      feasibility of deriving detailed anterior epicardial potential information using
      only 62 torso electrodes without the use of an a priori model.

PMID- 26216295
TI  - Debate on Naming of Biosimilars Continues.

PMID- 26216294
TI  - An Oncogenic NTRK Fusion in a Patient with Soft-Tissue Sarcoma with Response to
      the Tropomyosin-Related Kinase Inhibitor LOXO-101.
AB  - Oncogenic TRK fusions induce cancer cell proliferation and engage critical cancer
      related downstream signaling pathways. These TRK fusions occur rarely, but in a
      diverse spectrum of tumor histologies. LOXO-101 is an orally administered
      inhibitor of the TRK kinase and is highly selective only for the TRK family of
      receptors. Preclinical models of LOXO-101 using TRK-fusion-bearing human-derived
      cancer cell lines demonstrate inhibition of the fusion oncoprotein and cellular
      proliferation in vitro, and tumor growth in vivo. The tumor of a 41-year-old
      woman with soft-tissue sarcoma metastatic to the lung was found to harbor an LMNA
      NTRK1 gene fusion encoding a functional LMNA-TRKA fusion oncoprotein as
      determined by an in situ proximity ligation assay. In a phase I study of LOXO-101
      (ClinicalTrials.gov no. NCT02122913), this patient's tumors underwent rapid and
      substantial tumor regression, with an accompanying improvement in pulmonary
      dyspnea, oxygen saturation, and plasma tumor markers. SIGNIFICANCE: TRK fusions
      have been deemed putative oncogenic drivers, but their clinical significance
      remained unclear. A patient with a metastatic soft-tissue sarcoma with an LMNA
      NTRK1 fusion had rapid and substantial tumor regression with a novel, highly
      selective TRK inhibitor, LOXO-101, providing the first clinical evidence of
      benefit from inhibiting TRK fusions.

PMID- 26216296
TI  - Light-Activated Therapy Kills Cancer Cells.

PMID- 26216297
TI  - A2A adenosine receptor deletion is protective in a mouse model of Tauopathy.

PMID- 26216299
TI  - Sex differences in glutamate receptor gene expression in major depression and
      suicide.

PMID- 26216298
TI  - Neurexin 1 (NRXN1) splice isoform expression during human neocortical development
      and aging.
AB  - Neurexin 1 (NRXN1), a presynaptic cell adhesion molecule, is implicated in
      several neurodevelopmental disorders characterized by synaptic dysfunction
      including autism, intellectual disability and schizophrenia. To gain insight into
      NRXN1's involvement in human cortical development we used quantitative real-time
      PCR to examine the expression trajectories of NRXN1, and its predominant
      isoforms, NRXN1-alpha and NRXN1-beta, in prefrontal cortex from fetal stages to
      aging. In addition, we investigated whether prefrontal cortical expression levels
      of NRXN1 transcripts are altered in schizophrenia or bipolar disorder in
      comparison with non-psychiatric control subjects. We observed that all three
      NRXN1 transcripts were highly expressed during human fetal cortical development,
      markedly increasing with gestational age. In the postnatal dorsolateral
      prefrontal cortex, expression levels were negatively correlated with age, peaking
      at birth until ~3 years of age, after which levels declined markedly to be stable
      across the lifespan. NRXN1-beta expression was modestly but significantly
      elevated in the brains of patients with schizophrenia compared with non
      psychiatric controls, whereas NRXN1-alpha expression was increased in bipolar
      disorder. These data provide novel evidence that NRXN1 expression is highest in
      human dorsolateral prefrontal cortex during critical developmental windows
      relevant to the onset and diagnosis of a range of neurodevelopmental disorders,
      and that NRXN1 expression may be differentially altered in neuropsychiatric
      disorders. 

PMID- 26216300
TI  - Direct conversion of human fibroblasts to induced serotonergic neurons.
AB  - Serotonergic (5HT) neurons exert diverse and widespread functions in the brain.
      Dysfunction of the serotonergic system gives rise to a variety of mental
      illnesses including depression, anxiety, obsessive compulsive disorder, autism
      and eating disorders. Here we show that human primary fibroblasts were directly
      converted to induced serotonergic (i5HT) neurons by the expression of Ascl1,
      Foxa2, Lmx1b and FEV. The transdifferentiation was enhanced by p53 knockdown and
      appropriate culture conditions including hypoxia. The i5HT neurons expressed
      markers for mature serotonergic neurons, had Ca(2+)-dependent 5HT release and
      selective 5HT uptake, exhibited spontaneous action potentials and spontaneous
      excitatory postsynaptic currents. Application of serotonin significantly
      increased the firing rate of spontaneous action potentials, demonstrating the
      functional utility of i5HT neurons for studying serotonergic neurotransmission.
      The availability of human i5HT neurons will be very useful for research and drug
      discovery on many serotonin-related mental disorders. 

PMID- 26216301
TI  - High-throughput sequencing of the synaptome in major depressive disorder.
AB  - Major depressive disorder (MDD) is among the leading causes of worldwide
      disability. Despite its significant heritability, large-scale genome-wide
      association studies (GWASs) of MDD have yet to identify robustly associated
      common variants. Although increased sample sizes are being amassed for the next
      wave of GWAS, few studies have as yet focused on rare genetic variants in the
      study of MDD. We sequenced the exons of 1742 synaptic genes previously identified
      by proteomic experiments. PLINK/SEQ was used to perform single variant, gene
      burden and gene set analyses. The GeneMANIA interaction database was used to
      identify protein-protein interaction-based networks. Cases were selected from a
      familial collection of early-onset, recurrent depression and were compared with
      screened controls. After extensive quality control, we analyzed 259 cases with
      familial, early-onset MDD and 334 controls. The distribution of association test
      statistics for the single variant and gene burden analyses were consistent with
      the null hypothesis. However, analysis of prioritized gene sets showed a
      significant association with damaging singleton variants in a Cav2-adaptor gene
      set (odds ratio=2.6; P=0.0008) that survived correction for all gene sets and
      annotation categories tested (empirical P=0.049). In addition, we also found
      statistically significant evidence for an enrichment of rare variants in a
      protein-based network of 14 genes involved in actin polymerization and dendritic
      spine formation (nominal P=0.0031). In conclusion, we have identified a
      statistically significant gene set and gene network of rare variants that are
      over-represented in MDD, providing initial evidence that calcium signaling and
      dendrite regulation may be involved in the etiology of depression. 

PMID- 26216303
TI  - Structural and functional biology of arachidonic acid 15-lipoxygenase-1 (ALOX15).
AB  - Lipoxygenases (LOX) form a family of lipid peroxidizing enzymes, which have been
      implicated in a number of physiological processes and in the pathogenesis of
      inflammatory, hyperproliferative and neurodegenerative diseases. They occur in
      two of the three domains of terrestrial life (bacteria, eucarya) and the human
      genome involves six functional LOX genes, which encode for six different LOX
      isoforms. One of these isoforms is ALOX15, which has first been described in
      rabbits in 1974 as enzyme capable of oxidizing membrane phospholipids during the
      maturational breakdown of mitochondria in immature red blood cells. During the
      following decades ALOX15 has extensively been characterized and its biological
      functions have been studied in a number of cellular in vitro systems as well as
      in various whole animal disease models. This review is aimed at summarizing the
      current knowledge on the protein-chemical, molecular biological and enzymatic
      properties of ALOX15 in various species (human, mouse, rabbit, rat) as well as
      its implication in cellular physiology and in the pathogenesis of various
      diseases. 

PMID- 26216304
TI  - Role of cin-miR2118 in drought stress responses in Caragana intermedia and
      Tobacco.
AB  - The miR2118 is highly conserved in leguminous plants. Its function is to regulate
      the expression of genes encoding the TIR-NBS-LRR resistance protein. In this
      study, cin-miR2118 from Caragana intermedia was functionally characterized,
      especially with regard to its role in drought stress resistance. Two target genes
      of cin-miR2118 were predicted and cloned, the occurrence of miR2118 target
      sequence in both genes indicated that they might be targets of cin-miR2118. We
      investigated the expression patterns of cin-miR2118 and its target genes in C.
      intermedia stems and found diverse changes in expression in response to drought
      stress. CiDR1 was negatively correlated with corresponding miR2118 expression
      while CiDR2 was positively correlated with cin-miR2118. For further study,
      induced tolerance was observed in the transgenic Tobacco with overexpression cin
      miR2118 upon 140-min water deficiency. And the expression level of cin-miR2118
      was dramatically increased under drought stress. These results reveal that cin
      miR2118 exert positive effects on drought stress tolerance. In addition, our
      study unexpectedly found that overexpression of cin-miR2118 in Tobacco can cause
      phenotype changes, which suggested that cin-miR2118 may have a novel function as
      a growth regulator in Tobacco. 

PMID- 26216302
TI  - Microsomal epoxide hydrolase 1 (EPHX1): Gene, structure, function, and role in
      human disease.
AB  - Microsomal epoxide hydrolase (EPHX1) is an evolutionarily highly conserved
      biotransformation enzyme for converting epoxides to diols. Notably, the enzyme is
      able to either detoxify or bioactivate a wide range of substrates. Mutations and
      polymorphic variants in the EPHX1 gene have been associated with susceptibility
      to several human diseases including cancer. This review summarizes the key
      knowledge concerning EPHX1 gene and protein structure, expression pattern and
      regulation, and substrate specificity. The relevance of EPHX1 for human pathology
      is especially discussed. 

PMID- 26216306
TI  - Scientific publications in public, environmental and occupational health journals
      by authors from China, Japan and Korea in East Asia: A 10-year literature survey
      from 2003 to 2012.
AB  - OBJECTIVES: To compare the number and quality of public, environmental and
      occupational health articles published in international journals from the 3 major
      non-English speaking countries of East Asia: China, Japan and Korea. MATERIAL AND
      METHODS: Public, environmental and occupational health articles from China, Japan
      and Korea that were published in 161 journals from 2003 to 2012 were retrieved
      from the Science Citation Index Expanded (SCIE) database. We recorded the numbers
      of total articles, impact factors (IF), citations, number of articles in top 10
      journals, references as well as the article distribution from various regions in
      China. RESULTS: From 2003 to 2012, China, Japan and Korea published 5713, 3802
      and 1967 papers respectively, with accumulated impact factor of 14 934.55,
      8758.36 and 6189.25, the average impact factor of 2.61, 2.30 and 3.15 and the
      average citation numbers per document of 5.08, 6.49 and 5.25. In the top 10 high
      impact public, environmental and occupational health journals, China, Japan and
      Korea accounted for 50.19%, 20.34% and 29.47% of all the papers published in
      those journals, respectively. Total impact factors of the most popular 10 papers
      for China, Japan and Korea were: 26.23, 27.08 and 26.91. Distribution of
      scientific papers among regions was unbalanced in China, for Hong Kong and Taiwan
      it accounted for 47.31% of the papers from China. CONCLUSIONS: From 2003 to 2012,
      both the quality and number of papers from China published in public,
      environmental and occupational health journals have greatly improved. China
      exceeded Japan and Korea in the number, accumulated impact factor, total citation
      times and the average number of references, while Korea had the highest average
      impact factor. Japan had the highest journal impact factor among the most popular
      journals, and the highest average citation number per document.

PMID- 26216305
TI  - Outdoor particulate matter (PM) and associated cardiovascular diseases in the
      Middle East.
AB  - Air pollution is a widespread environmental concern. Considerable epidemiological
      evidence indicates air pollution, particularly particulate matter (PM), as a
      major risk factor for cardiovascular diseases (CVD) in the developed countries.
      The main objective of our review is to assess the levels and sources of PM across
      the Middle East area and to search evidence for the relationship between PM
      exposure and CVD. An extensive review of the published literature pertaining to
      the subject (2000-2013) was conducted using PubMed, Medline and Google Scholar
      databases. We reveal that low utilization of public transport, ageing vehicle
      fleet and the increasing number of personal cars in the developing countries all
      contribute to the traffic congestion and aggravate the pollution problem. The
      annual average values of PM pollutants in the Middle East region are much higher
      than the World Health Organization 2006 guidelines (PM2.5 = 10 MUg/m(3), PM10 =
      20 MUg/m(3)). We uncover evidence on the association between PM and CVD in 4
      Middle East countries: Iran, Kingdom of Saudi Arabia, Qatar and the United Arab
      Emirates. The findings are in light of the international figures. Ambient PM
      pollution is considered a potential risk factor for platelet activation and
      atherosclerosis and has been found to be linked with an increased risk for
      mortality and hospital admissions due to CVD. This review highlights the
      importance of developing a strategy to improve air quality and reduce outdoor air
      pollution in the developing countries, particularly in the Middle East. Future
      studies should weigh the potential impact of PM on the overall burden of cardiac
      diseases.

PMID- 26216307
TI  - Utilizing the metabolic syndrome component count in workers' health surveillance:
      An example of day-time vs. day-night rotating shift workers.
AB  - OBJECTIVES: To establish a practical method for assessing the general metabolic
      health conditions among different employee groups, this study utilized the total
      count of metabolic syndrome (MetS) elements as a parameter, and performed a
      retrospective analysis comparing changes of MetS component count (MSC) of 5 years
      among day-time work (DW) and day-andnight rotating shift work (RSW) employees.
      MATERIAL AND METHODS: The data of personal histories, physical examinations,
      blood tests, abdominal sonographic examinations and occupational records were
      collected from a cohort of workers in an electronics manufacturing company. We
      first defined the arithmetic mean value of MSC as MSC density (MSCD) for the
      employee group; then we compared the changes of MSCD over 5 years between DW and
      RSW workers. Occupational, personal and health records were analyzed for the 1077
      workers with an initial mean age of 32.4 years (standard deviation (SD): 6.2
      years), including 565 RSW workers (52%). RESULTS: The initial MSCDs were 1.26 and
      1.12 (p = 0.06) for DW and RSW workers, respectively; after 5 years, the
      increments of MSCD for DW and RSW workers were 0.10 and 0.39, respectively (p <
      0.01). By performing multivariate logistic regression analyses, and comparing
      with DW co-workers, final results indicated that the workers exposed to RSW have
      1.7-fold increased risk of elevated MSCD (95% confidence interval (CI): 1.28
      2.25, p < 0.01); and are 38% less likely (adjusted rate ratio (aRR) 0.62, 95% CI:
      0.45-0.86, p < 0.01) to attain decreased MSCD. CONCLUSIONS: These observations
      demonstrate that changes of MSCD are significantly different between DW and RSW
      workers, and are increasingly associated with RSW exposure. In conclusion, MSCD
      can represent the general metabolic health conditions of a given employee group;
      MSC, MSCD and their transitional changes can be applied as simple and
      standardized tools for monitoring metabolic health risk profiles when managing
      employee health, at both the individual and company levels.

PMID- 26216308
TI  - Do all types of restructuring threaten employees' well-being? An exploratory
      study.
AB  - OBJECTIVES: Most research on the negative impact of restructuring on employees'
      health considers restructuring involving personnel reduction. The aim of this
      study was to explore the assumption that the type of restructuring, business
      expansion versus restructuring not involving expansion (only reductions and/or
      change of ownership), influences its psychological responses: appraisal of the
      change, psychosocial working conditions and well-being after the change. MATERIAL
      AND METHODS: The study was carried out among 857 employees that experienced
      restructuring in 2009 and/or 2010 and 538 employees from companies not
      restructured at that time. The main variables, i.e., assessment of change in
      terms of personal benefits and losses, psychosocial job characteristics and well
      being were measured using a questionnaire developed in "The psychological health
      and well-being in restructuring: key effects and mechanisms" project (PSYRES).
      RESULTS: It was found that the employees who experienced business expansion in
      comparison to those who experienced exclusively change of ownership had a higher
      appraisal of change, while those who experienced restructuring not involving
      business expansion did not differ from those who experienced change of ownership.
      As far as psychosocial working conditions are concerned, those employees who
      experienced exclusively business expansion did not differ from those in the not
      restructured companies (except for quantitative demands that were higher), while
      most psychosocial working conditions of the employees who experienced
      restructuring not involving expansion were poorer than in the not restructured
      companies. Also, well-being measures of the employees who experienced exclusively
      business expansion did not differ from those in the not restructured companies
      (except for innovative behavior that was even higher), while well-being measure
      of those who experienced restructuring not involving expansion was poorer than of
      those in the not restructured companies. CONCLUSIONS: Restructuring involving
      exclusively business expansion is not a threat to psychosocial job
      characteristics (except for quantitative demands) or to employees' well-being.
      Therefore, the type of restructuring should be taken into account when the
      restructuring--psychological health relationship is discussed.

PMID- 26216309
TI  - Relation between resiliency and post-traumatic growth in a group of paramedics:
      The mediating role of coping strategies.
AB  - OBJECTIVES: The purpose of the research is to investigate the mediating role of
      coping strategies for stress in the relation between resiliency and post
      traumatic growth in a group of paramedics. MATERIAL AND METHODS: Data of 80
      paramedics who have experienced traumatic event at their worksites was analyzed.
      The age range of the participants was 21-67 years old (mean: 35.47, standard
      deviation: 10.21). The Post-traumatic Growth Inventory, the Assessment Resiliency
      Scale and Inventory to Measure Coping Strategies for Stress--Mini-Cope were used
      in the study. RESULTS: Venting of negative emotions and denial appeared as
      suppressors in analyzing the relation, while planning plays mediating role
      between resiliency and post-traumatic growth. CONCLUSIONS: In the process of post
      traumatic growth, both avoidance and problem-focused strategies are important.
      Moreover, controlling such strategies as Venting and Denial may result in a high
      level of posttraumatic growth in the study group. The data supports that
      resiliency may have direct or indirect impact on post-traumatic changes. The
      results allow to understand the mechanisms of resiliency better, that
      relationship with post-traumatic growth is ambiguous.

PMID- 26216310
TI  - The prevalence of excessive daytime sleepiness among academic physicians and its
      impact on the quality of life and occupational performance.
AB  - OBJECTIVES: Sleep disorders can affect health and occupational performance of
      physicians as well as outcomes in patients. The purpose of this study was to
      assess the prevalence of excessive daytime sleepiness (EDS) measured by the
      Epworth Sleepiness Scale (ESS) among academic physicians at a tertiary academic
      medical center in an urban area in the northwest region of Turkey, and to
      establish a relationship between the self-perceived sleepiness and the quality of
      life using the EuroQol-5 dimensions (EQ-5D). MATERIAL AND METHODS: A
      questionnaire prepared by the researchers after scanning the literature on the
      subject was e-mailed to the academic physicians of a tertiary academic medical
      center in Istanbul. The ESS and the EQ-5D were also included in the survey. The e
      mail database of the institution directory was used to compile a list of active
      academic physicians who practiced clinical medicine. Paired and independent t
      tests were used for the data analysis at a significance level of p < 0.05.
      RESULTS: Three hundred and ninety six academic physicians were e-mailed and a
      total of 252 subjects replied resulting in a 63.6% response rate. There were 84
      (33.3%) female and 168 (66.7%) male academic physicians participating in the
      study. One hundred and eight out of 252 (42.8%) academic physicians were taking
      night calls (p < 0.001). Ninety study subjects (35.7%) felt they had enough sleep
      and 84 (33.3%) reported napping daily (p < 0.001). In our sample, 28.6% (N = 72)
      of the physicians felt sleepy during the day (ESS score > 10) (p < 0.001). In the
      case of the EQ-5D index and visual analogue scale of the EQ-5D questionnaire (EQ
      5D VAS), the status of sleepiness of academic physicians was associated with a
      poorer quality of life (p < 0.001). CONCLUSIONS: More than a 1/4 of the academic
      physicians suffered from sleepiness. There was an association between the poor
      quality of life and daytime sleepiness. There was also a positive relationship
      between habitual napping and being sleepy during the day.

PMID- 26216311
TI  - Feasibility and acceptability of a workers' health surveillance program for
      hospital physicians.
AB  - OBJECTIVES: A Workers' Health Surveillance (WHS) program is an occupational
      health strategy used to detect and address the health of individual workers to
      improve their ability to work. This study aims to investigate the feasibility and
      acceptability of a new job-specific WHS for hospital physicians. MATERIAL AND
      METHODS: All hospital physicians of the general surgery, radiotherapy and
      obstetrics and gynecology departments from 1 academic hospital were invited to
      participate in the WHS by the in-company occupational health service. An
      occupational physician and a medical assistant were trained to use the protocol.
      Feasibility was operationalized as the received and delivered dose, observed
      success factors and potential obstacles. Acceptability was assessed by asking
      whether the WHS was desirable and feasible for future use and by estimating the
      effects on health and work ability. Written questions and semi-structured
      interviews were conducted with the participating physicians, 5 department
      managers and the 2 occupational health professionals involved in the study.
      RESULTS: One-third of the hospital physicians (34%) participated in every part of
      the WHS. The delivered dose was 77/84 (92%). Almost all hospital physicians who
      received recommendations expected to adhere to this advice. The study
      participants appreciated the organization of the WHS. This WHS was positively
      graded (8 out of 10 max) in terms of acceptability. Positive effects of the WHS
      on health, work functioning and long-term work ability were perceived by 2/3 of
      the physicians. CONCLUSIONS: The new job-specific WHS for hospital physicians
      showed good feasibility and acceptability among participating hospital
      physicians, occupational health professionals and medical managers.

PMID- 26216312
TI  - Professional and social activity of patients after heart transplant.
AB  - OBJECTIVES: The aim of the study is to describe both professional and social
      activities of patients after heart transplant. MATERIAL AND METHODS: Ninety-five
      heart transplant patients treated at the Silesian Center for Heart Diseases in
      Zabrze were surveyed, comprising 29 women (30.5%) and 66 men (69.5%). The average
      age of respondents was 54.3 years old (standard deviation (SD) = 15 years); the
      average period that had elapsed since the heart transplant was 7.1 years (SD = 4
      years). We designed a questionnaire as a tool for collecting information from
      patients. RESULTS: Twenty-five percent of patients worked at the time of
      completion of the questionnaire. Eighty percent of those patients were working
      before and after the transplant, 20%--only after transplantation (p < 0.05). A
      different job position at a new workplace had 47.8% of patients, 34.8% of them
      had the same job position at the same work place as they had had before, 63.4% of
      the heart transplant respondents were pensioners. Eighty-two percent of patients
      had a certificate with a designated degree of disability--among them: 69% had a
      certificate for a significant degree of disability, 22%--for a moderate degree of
      disability. Among those surveyed, 52.5% said that their financial situation had
      not changed whereas 34.5% of those surveyed reported a change for the worse.
      Thirty-seven percent of respondents reported changes in family relationships.
      Seventy-seven percent reported that they received help from family members, as
      compared with 19% who did not. CONCLUSIONS: Only 25.3% of the patients treated at
      the Silesian Centre for Heart Diseases after heart transplant are employed and it
      is one of the lowest employment rates in this category of patients in Europe. One
      third of working patients have the same work place as they had before their
      operation. Heart transplant is a cause of changes in family relationships. Most
      often family bonds are strengthened but sometimes family members become nervous,
      impatient and unwilling to talk about the transplant.

PMID- 26216313
TI  - Influence of electromagnetic field (1800 MHz) on lipid peroxidation in brain,
      blood, liver and kidney in rats.
AB  - OBJECTIVES: The aim of this study is the evaluation of the influence of repeated
      (5 times for 15 min) exposure to electromagnetic field (EMF) of 1800 MHz
      frequency on tissue lipid peroxidation (LPO) both in normal and inflammatory
      state, combined with analgesic treatment. MATERIAL AND METHODS: The concentration
      of malondialdehyde (MDA) as the end-product of the lipid peroxidation (LPO) was
      estimated in blood, liver, kidneys, and brain of Wistar rats, both healthy and
      those with complete Freund's adjuvant (CFA)-induced persistent paw inflammation.
      RESULTS: The slightly elevated levels of the MDA in blood, kidney, and brain were
      observed among healthy rats in electromagnetic field (EMF)-exposed groups,
      treated with tramadol (TRAM/EMF and exposed to the EMF). The malondialdehyde
      remained at the same level in the liver in all investigated groups: the control
      group (CON), the exposed group (EMF), treated with tramadol (TRAM) as well as
      exposed to and treated with tramadol (TRAM/EMF). In the group of animals treated
      with the complete Freund's adjuvant (CFA) we also observed slightly increased
      values of the MDA in the case of the control group (CON) and the exposed groups
      (EMF and TRAM/EMF). The MDA values concerning kidneys remained at the same levels
      in the control, exposed, and not-exposed group treated with tramadol. Results for
      healthy rats and animals with inflammation did not differ significantly.
      CONCLUSIONS: The electromagnetic field exposure (EMF), applied in the repeated
      manner together with opioid drug tramadol (TRAM), slightly enhanced lipid
      peroxidation level in brain, blood, and kidneys.

PMID- 26216314
TI  - The impact of professional status on the effects of and adherence to the
      outpatient followed by home-based telemonitored cardiac rehabilitation in
      patients referred by a social insurance institution.
AB  - OBJECTIVES: Legislators and policymakers have expressed strong interest in
      intervention programs to reduce dependence on social disability benefits. Hybrid:
      ambulatory followed by home-based cardiac telerehabilitation--hybrid cardiac
      rehabilitation (HCR) seems to be a novel alternative for standard cardiac
      rehabilitation for patients with cardiovascular diseases (CVD) as a form of
      pension prevention paid by the Social Insurance Institution (SII). The kind of
      professional status may bias the motivation to return to work after HCR. The aim
      of our study was to evaluate whether the professional status can affect the
      effects of HCR. MATERIAL AND METHODS: One hundred fifty-two patients with CVD
      referred by the SII for a 5-week HCR were qualified for the study. Patients
      (87.7% males), aged 57.31 +/- 5.61 years, were divided into 2 subgroups: W) white
      collar employees (N = 22) and B) blue-collar employees (N = 130). To evaluate
      functional capacity, an exercise test on a treadmill was used. RESULTS: The
      number of days of absence in the cardiac rehabilitation program did not differ
      between the groups (mean +/- standard deviation--B: 1.09 +/- 3.10 days, W: 1.95
      +/- 3.64 days). There were significant improvements (p < 0.05) in measured
      variables after HCR in both (W and B) groups (max workload: 8.21 +/- 2.88 METs
      (measured in metabolic equivalents) vs. 9.6 +/- 2.49 METs, 7.76 +/- 2.51 METs vs.
      8.73 +/- 2.7 METs, resting heart rate (RHR): 77 +/- 16.22 bpm vs. 69.94 +/- 12.93
      bpm, 79.59 +/- 14 bpm vs. 75.24 +/- 11.87 bpm; double product, i.e., product of
      heart rate and systolic BP (DP rest) 10 815.22 +/- 2968.24 vs. 9242.94 +/-
      1923.08, 10 927.62 +/- 2508.47 vs. 9929.7 +/- 2304.94). In group B, a decrease in
      systolic blood pressure (BP syst. - 137.03 +/- 17.14 mm Hg vs. 131.82 +/- 21.13
      mm Hg), heart rate recovery in the 1st minute after the end of peak exercise
      (HRR1) (99.38 +/- 19.25 vs. 93.9 +/- 19.48) and New York Heart Association (NYHA)
      class (1.22 +/- 0.53 vs. 1.11 +/- 0.36) was observed. In group W, a decrease in
      diastolic blood pressure (BP diast.) at rest was observed (88.28 +/- 9.79 mm Hg
      vs. 83.39 +/- 8.95 mm Hg). The decrease in resting HR was significantly greater
      in group W (69.94 +/- 12.93 vs. 75.24 +/- 11.87, p = 0.034). CONCLUSIONS: Hybrid
      cardiac rehabilitation is feasible and safe with high adherence to the program
      regardless of the patient's professional status. Professional status did not
      influence the beneficial effect of HCR on exercise tolerance.

PMID- 26216315
TI  - Ambient ozone and bacterium Streptococcus: A link between cellulitis and
      pharyngitis.
AB  - OBJECTIVES: Ambient air pollution, as many publications indicate, may have
      associations with skin condition. The aim of this study has been to examine such
      common relations for cellulitis and pharyngitis. The hypothesis is that ambient
      ground-level ozone may help bacteria to penetrate skin or throat. MATERIAL AND
      METHODS: We used the emergency department (ED) visits data in Edmonton, Canada
      for the period from 1992 (April) to 2002 (March). We retrieved all the diagnosed
      ED visits for cellulitis and pharyngitis. Case-crossover design was used to study
      potential association between ozone and those visits. Conditional logistic
      regression was used to estimate odds ratios (OR) and their 95% confidence
      intervals (95% CI). RESULTS: The results are reported for the interquartile range
      (IQR = 17.9 ppb) for 8 h maximum ozone. Positive and statistical significant
      results were obtained as follows: for lags from 0 to 3 (OR = 1.07, 95% CI: 1.03
      1.12, lag 2); for lags from 0 to 6 days (OR = 1.08, 95% CI: 1.03-1.12, lag 3);
      for lags from 0 to 4 (OR = 1.06, 95% CI: 1.03-1.09, for lag 2 and 3).
      CONCLUSIONS: The findings suggest the response to exposure to ambient ground
      level ozone for skin and pharyngitis considered separately and jointly.

PMID- 26216316
TI  - Acute exacerbation of idiopathic pulmonary fibrosis after inhalation of a water
      repellent.
AB  - The natural course of idiopathic pulmonary fibrosis (IPF) is unpredictable at the
      time of diagnosis. Some patients may experience episodes of acute respiratory
      worsening that have been termed acute exacerbations. A 58-year-old male was
      admitted to our Emergency Department due to progressive and intense dyspnea and
      dry cough after accidental inhalation of waterproof's vapor containing siloxanes.
      Chest high resolution computed tomography (HRCT) scan showed diffuse and
      bilateral ground glass attenuation, basal predominant reticular abnormalities and
      subpleural honeycombing. The patient didn't know that he suffered from IPF and
      siloxanes' inhalation triggered an acute exacerbation of his disease. Clinical
      course after the inhalation was aggressive and, despite steroids and
      cyclophosphamide therapy, the patient died 3 months after due to a respiratory
      failure. Inhalation of water repellents has been associated with an acute onset
      of respiratory symptoms and acute lung injury; usually, however, the prognosis is
      commonly good with a complete recovery. Our case is an example of an extremely
      negative reaction probably because of pre-existing and misdiagnosed IPF.
      Currently, no literature concerning water repellent inhalation as a trigger of
      acute exacerbation of IPF is available. 

PMID- 26216317
TI  - Effect of lignocellulose-derived inhibitors on the growth and D-lactic acid
      production of Sporolactobacillus inulinus YBS1-5.
AB  - The impact of lignocellulose-derived inhibitors on the cell growth and D-lactic
      production of Sporolactobacillus inulinus YBS1-5 was investigated. At high
      concentrations, both furans and phenolics, such as furfural, HMF, syringaldehyde
      and vanillin, affected cell growth and D-lactic acid production and
      syringaldehyde exhibited the highest. Further experiments showed that only
      vanillin caused cellular membrane damage. Based on the Biolog approach, in vivo
      studies on intact S. inulinus cells indicated that phenolics had a stronger
      inhibitory effect than furan derivatives on the metabolic activity of the
      concerned substrates related with the key enzymes of D-lactic acid fermentation.
      The direct in vitro inhibitory effect of the model compounds on the four key
      enzymes displayed similar patterns. Syringaldehyde was the strongest inhibitor.
      In general, comparison with published results for other microorganisms indicated
      that strain YBS1-5 was a robust microorganism against inhibitors of
      lignocellulose hydrolysate. Notably, in concentrated corn stover hydrolysate, S.
      inulinus YBS1-5 produced 70.7 g/L D-lactic acid, which was 87.7 % of the yield
      from the control experiment. However, the fermentation time was prolonged 36 h.
      In order to improve fermentation rate, a detoxification technology or more robust
      mutant to phenolics especially syringaldehyde should be developed. 

PMID- 26216318
TI  - Double strand break repair by capture of retrotransposon sequences and reverse
      transcribed spliced mRNA sequences in mouse zygotes.
AB  - The CRISPR/Cas system efficiently introduces double strand breaks (DSBs) at a
      genomic locus specified by a single guide RNA (sgRNA). The DSBs are subsequently
      repaired through non-homologous end joining (NHEJ) or homologous recombination
      (HR). Here, we demonstrate that DSBs introduced into mouse zygotes by the
      CRISPR/Cas system are repaired by the capture of DNA sequences deriving from
      retrotransposons, genomic DNA, mRNA and sgRNA. Among 93 mice analysed, 57 carried
      mutant alleles and 22 of them had long de novo insertion(s) at DSB-introduced
      sites; two were spliced mRNAs of Pcnt and Inadl without introns, indicating the
      involvement of reverse transcription (RT). Fifteen alleles included
      retrotransposons, mRNAs, and other sequences without evidence of RT. Two others
      were sgRNAs with one containing T7 promoter-derived sequence suggestive of a PCR
      product as its origin. In conclusion, RT-product-mediated DSB repair (RMDR) and
      non-RMDR repair were identified in the mouse zygote. We also confirmed that both
      RMDR and non-RMDR take place in CRISPR/Cas transfected NIH-3T3 cells. Finally, as
      two de novo MuERV-L insertions in C57BL/6 mice were shown to have characteristic
      features of RMDR in natural conditions, we hypothesize that RMDR contributes to
      the emergence of novel DNA sequences in the course of evolution. 

PMID- 26216319
TI  - Predicting Discharge Dates From the NICU Using Progress Note Data.
AB  - BACKGROUND AND OBJECTIVES: Discharging patients from the NICU may be delayed for
      nonmedical reasons including the need for medical equipment, parental education,
      and children's services. We describe a method to predict which patients will be
      medically ready for discharge in the next 2 to 10 days, providing lead time to
      address nonmedical reasons for delayed discharge. METHODS: A retrospective study
      examined 26 features (17 extracted, 9 engineered) from daily progress notes of
      4693 patients (103,206 patient-days) from the NICU of a large, academic
      children's hospital. These data were used to develop a supervised machine
      learning problem to predict days to discharge (DTD). Random forest classifiers
      were trained by using examined features and International Classification of
      Diseases, Ninth Revision-based subpopulations to determine the most important
      features. RESULTS: Three of the 4 subpopulations (premature, cardiac,
      gastrointestinal surgery) and all patients combined performed similarly at 2, 4,
      7, and 10 DTD with area under the curve (AUC) ranging from 0.854 to 0.865 at 2
      DTD and 0.723 to 0.729 at 10 DTD. Patients undergoing neurosurgery performed
      worse at every DTD measure, scoring 0.749 at 2 DTD and 0.614 at 10 DTD. This
      model was also able to identify important features and provide "rule-of-thumb"
      criteria for patients close to discharge. By using DTD equal to 4 and 2 features
      (oral percentage of feedings and weight), we constructed a model with an AUC of
      0.843. CONCLUSIONS: Using clinical features from daily progress notes provides an
      accurate method to predict when patients in the NICU are nearing discharge.

PMID- 26216320
TI  - Outbreak of Mycoplasma pneumoniae-Associated Stevens-Johnson Syndrome.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS) is an uncommon, sporadic disease and
      outbreaks are rare. In November 2013, an outbreak of SJS was identified at
      Children's Hospital Colorado. METHODS: Outbreak cases were children aged 5-21
      with a discharge diagnosis of SJS admitted from September 1 to November 30, 2013.
      Medical charts were reviewed using standardized data collection forms.
      Respiratory specimens were tested for viruses and Mycoplasma pneumoniae (Mp) by
      polymerase chain reaction (PCR). We conducted a separate 4-year retrospective
      case-control study comparing hospitalized SJS cases with and without evidence of
      Mp infection. RESULTS: During the outbreak, 8 children met SJS criteria. Median
      age was 11.5 years (range 8-16 years); 5 (63%) were boys and 5 (63%) were Mp-PCR
      positive. Of the 5 PCR-positive children, none had preceding medication exposure,
      and all had radiographic pneumonia. All outbreak Mp isolates were macrolide
      susceptible. The retrospective case-control analysis showed that Mp-associated
      SJS episodes (n = 17) were more likely to have pneumonia (odds ratio [OR] 7.5,
      confidence interval [CI] 1.6-35.1), preceding respiratory symptoms (OR 30.0, CI
      3.3-269.4) [corrected] an erythrocyte sedimentation rate >=35 mg/dL (OR 22.8, CI
      2.1-244.9), and <=3 affected skin sites (OR 4.5, CI 1.2-17.4) than non-Mp
      associated SJS episodes (n = 23). CONCLUSIONS: We report the largest outbreak of
      SJS in children, which was also predominately associated with Mp infection. Mp
      associated SJS was associated with a distinct clinical presentation that included
      less extensive skin disease, an elevated erythrocyte sedimentation rate, and
      evidence of a preceding respiratory infection.

PMID- 26216321
TI  - Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in
      Neurodevelopmental Disorders?
AB  - The diuretic agent bumetanide has recently been put forward as a novel, promising
      treatment of behavioral symptoms in autism spectrum disorder (ASD) and related
      conditions. Bumetanide can decrease neuronal chloride concentrations and may
      thereby reinstate gamma-aminobutyric acid (GABA)-ergic inhibition in patients
      with neurodevelopmental disorders. However, strategies to select appropriate
      candidates for bumetanide treatment are lacking. We hypothesized that a
      paradoxical response to GABA-enforcing agents such as benzodiazepines may predict
      the efficacy of bumetanide treatment in neurodevelopmental disorders. We describe
      a case of a 10-year-old girl with ASD, epilepsy, cortical dysplasia, and a
      15q11.2 duplication who had exhibited marked behavioral arousal after previous
      treatment with clobazam, a benzodiazepine. We hypothesized that this response
      indicated the presence of depolarizing excitatory GABA and started bumetanide
      treatment with monitoring of behavior, cognition, and EEG. The treatment resulted
      in a marked clinical improvement in sensory behaviors, rigidity, and memory
      performance, which was substantiated by questionnaires and cognitive assessments.
      At baseline, the girl's EEG showed a depression in absolute alpha power, an
      electrographic sign previously related to ASD, which was normalized with
      bumetanide treatment. The effects of bumetanide on cognition and EEG seemed to
      mirror the "nonparadoxical" responses to benzodiazepines in healthy subjects. In
      addition, temporal lobe epilepsy and cortical dysplasia have both been linked to
      disturbed chloride homeostasis and seem to support our assumption that the
      observed paradoxical response was due to GABA-mediated excitation. This case
      highlights that a paradoxical behavioral response to GABA-enforcing drugs may
      constitute a framework for targeted treatment with bumetanide. 

PMID- 26216322
TI  - Maternal Report of Advice Received for Infant Care.
AB  - BACKGROUND: Advice has been associated with increased adherence to recommended
      infant care practices, and may represent a modifiable factor to promote infant
      health. METHODS: A stratified, 2-stage, clustered design, with oversampling of
      black and Hispanic mothers, was used to survey a nationally representative sample
      of 1031 mothers of infants aged 2 to 6 months. Survey questions assessed advice
      received from doctors, birth hospital nurses, family, and media regarding
      immunization, breastfeeding, sleep position, sleep location, and pacifier use.
      Weighted frequencies of no advice and advice consistent with recommendations were
      calculated to obtain prevalence estimates. Multivariable logistic regression
      analyses were performed to assess factors associated with receipt of
      recommendation consistent advice. RESULTS: Although doctors were the most
      prevalent source of reported advice, ~20% of mothers reported no doctor advice
      for breastfeeding or sleep position, and more than 50% reported no advice
      regarding sleep location or pacifier use. Reported advice from nurses was
      generally similar to doctors. The prevalence of any advice from family or media
      was 20% to 56% for nearly all care practices, and advice given was often
      inconsistent with recommendations. The only factors that were consistently
      associated with receipt of recommendation consistent advice were race/ethnicity
      and parity; black and Hispanic mothers and first-time mothers were more likely to
      report recommendation consistent advice. CONCLUSIONS: Mothers commonly report
      receiving either no advice or recommendation inconsistent advice from each of the
      4 sources we studied. By identifying care practices with low prevalence of
      recommendation consistent advice from potentially important advisors, our
      findings highlight opportunities for future intervention.

PMID- 26216323
TI  - Thrombocytopenia in Small-for-Gestational-Age Infants.
AB  - BACKGROUND: Thrombocytopenia is common among small-for-gestational-age (SGA)
      neonates (birth weight <10th percentile reference range), but several aspects of
      this thrombocytopenia are unclear, including the incidence, typical nadir,
      duration, association with preeclampsia, mechanism, and risk of death. METHODS:
      Using 9 years of multihospital records, we studied SGA neonates with >=2 platelet
      counts <150,000/MUL in their first week. RESULTS: We found first-week
      thrombocytopenia in 31% (905 of 2891) of SGA neonates versus 10% of non-SGA
      matched controls (P < .0001). Of the 905, 102 had a recognized cause of
      thrombocytopenia (disseminated intravascular coagulation, early-onset sepsis, or
      extracorporeal membrane oxygenation). This group had a 65% mortality rate. The
      remaining 803 did not have an obvious cause for their thrombocytopenia, and we
      called this "thrombocytopenia of SGA." They had a mortality rate of 2% (P <
      .0001) and a mean nadir count on day 4 of 93,000/MUL (SD 51,580/MUL, 10th
      percentile 50,000/MUL, 90th percentile 175,000/MUL). By day 14, platelet counts
      were >=150,000/MUL in more than half of the patients. Severely SGA neonates (<1st
      percentile) had lower counts and longer thrombocytopenia duration (P < .001).
      High nucleated red cell counts at birth correlated with low platelets (P <
      .0001). Platelet transfusions were given to 23%, and counts typically more than
      tripled. Thrombocytopenia was more associated with SGA status than with the
      diagnosis of maternal preeclampsia. CONCLUSIONS: SGA neonates with clearly
      recognized varieties of thrombocytopenia have a high mortality rate. In contrast,
      thrombocytopenia of SGA is a hyporegenerative condition of moderate severity and
      2 weeks' duration and is associated with evidence of intrauterine hypoxia and a
      low mortality rate.

PMID- 26216324
TI  - Variation in Prenatal Diagnosis of Congenital Heart Disease in Infants.
AB  - BACKGROUND AND OBJECTIVE: Prenatal diagnosis allows improved perioperative
      outcomes for fetuses with certain forms of congenital heart disease (CHD).
      Variability in prenatal diagnosis has been demonstrated in other countries,
      leading to efforts to improve fetal imaging protocols and access to care, but has
      not been examined across the United States. The objective was to evaluate
      national variation in prenatal detection across geographic region and defect type
      in neonates and infants with CHD undergoing heart surgery. METHODS:
      Cardiovascular operations performed in patients <=6 months of age in the United
      States and included in the Society of Thoracic Surgeons Congenital Heart Surgery
      Database (2006-2012) were eligible for inclusion. Centers with >15% missing
      prenatal diagnosis data were excluded from the study. Prenatal diagnosis rates
      were compared across geographic location of residence and defect type using the
      chi(2) test. RESULTS: Overall, the study included 31,374 patients from 91 Society
      of Thoracic Surgeons Congenital Heart Surgery Database participating centers
      across the United States. Prenatal detection occurred in 34% and increased every
      year, from 26% (2006) to 42% (2012). There was significant geographic variation
      in rates of prenatal diagnosis across states (range 11.8%-53.4%, P < .0001).
      Significant variability by defect type was also observed, with higher rates for
      lesions identifiable on 4-chamber view than for those requiring outflow tract
      visualization (57% vs 32%, P < .0001). CONCLUSIONS: Rates of prenatal CHD
      detection in the United States remain low for patients undergoing surgical
      intervention, with significant variability between states and across defect type.
      Additional studies are needed to identify reasons for this variation and the
      potential impact on patient outcomes.

PMID- 26216325
TI  - Positive Parenting Practices, Health Disparities, and Developmental Progress.
AB  - OBJECTIVE: To describe interactive activities between parents and young children
      in a nationally representative sample. We hypothesized that the frequency of
      participation in interactive activities would be different across economic strata
      and would be associated with developmental delay. METHODS: Children 4 to 36
      months of age were identified by using The National Survey of Children's Health
      2011-2012. Interactive caregiving practices were reported by poverty status.
      Developmental concerns were derived from caregiver responses and scoring of the
      Parents Evaluation of Developmental Status. Multivariable logistic regressions
      with weighting were used to explore the effect of interactive practices on risk
      for developmental delay across poverty levels. Covariates including age, gender,
      insurance type, maternal education, parenting stress, and ethnicity were adjusted
      in the models. RESULTS: In our sample (n = 12,642), caregivers with the lowest
      income versus highest income reported lower participation in reading (33% vs 64%;
      P < .0001), singing or telling stories (52% vs 77%, P < .0001), and taking their
      child on an outing (13% vs 22%, P < .0001). Less frequent participation in
      interactive activities during the week were associated with increased risk of
      developmental delay among low-income families (Reading odds ratio [OR] 1.57, 95%
      confidence interval [CI] 1.15-2.13; Singing songs/Telling Stories OR 1.66, 95% CI
      1.15-2.40; Outings OR 1.48, 95% CI 1.11-1.97). CONCLUSIONS: Despite evidence
      emphasizing the protective effects of supportive parenting practices on early
      child development, our work demonstrates significant disparities in parenting
      practices that promote early child development between economically advantaged
      and disadvantaged parents. Innovative population-level strategies that enrich
      parenting practices for vulnerable children in early childhood are needed.

PMID- 26216327
TI  - Understanding Outcomes in Adolescent Bariatric Surgery.

PMID- 26216326
TI  - Psychosocial Factors Associated With Adolescent Electronic Cigarette and
      Cigarette Use.
AB  - BACKGROUND: Use of electronic cigarettes (e-cigarettes) among adolescents has
      increased since their introduction into the US market in 2007. Little is known
      about the role of e-cigarette psychosocial factors on risk of e-cigarette or
      cigarette use in adolescence. METHODS: Information on e-cigarette and cigarette
      psychosocial factors (use and attitudes about use in the home and among friends)
      was collected from 11th- and 12th-grade participants in the Southern California
      Children's Health Study during the spring of 2014. RESULTS: Of 2084 participants,
      499 (24.0%) had used an e-cigarette, including 200 (9.6%) current users (past 30
      days); 390 participants (18.7%) had smoked a combustible cigarette, and 119
      (5.7%) were current cigarette smokers. Cigarette and e-cigarette use were
      correlated. Nevertheless, 40.5% (n = 81) of current e-cigarette users had never
      smoked a cigarette. Psychosocial factors (home use of each product, friends' use
      of and positive attitudes toward e-cigarettes and cigarettes) and participant
      perception of the harm of e-cigarettes were strongly positively associated both
      with e-cigarette and cigarette use. Most youth who reported e-cigarette use had
      friends who used e-cigarettes, and almost half of current users reported that
      they did not believe there were health risks associated with e-cigarette use.
      CONCLUSIONS: Longitudinal studies of adolescents are needed to determine whether
      the strong association of e-cigarette psychosocial factors with both e-cigarette
      and cigarette use will lead to increased cigarette use or dual use of cigarettes
      and e-cigarettes, or whether e-cigarettes will serve as a gateway to cigarette
      use.

PMID- 26216330
TI  - Parental Advice: Given Perhaps, but Not Received.

PMID- 26216329
TI  - A Longitudinal Study of Pediatricians Early in Their Careers: PLACES.
AB  - The American Academy of Pediatrics (AAP) launched the Pediatrician Life and
      Career Experience Study (PLACES), a longitudinal study that tracks the personal
      and professional experiences of early career pediatricians, in 2012. We used a
      multipronged approach to develop the study methodology and survey domains and
      items, including review of existing literature and qualitative research with the
      target population. We chose to include 2 cohorts of US pediatricians on the basis
      of residency graduation dates, including 1 group who were several years out of
      residency (2002-2004 Residency Graduates Cohort) and a second group who recently
      graduated from residency at study launch (2009-2011 Residency Graduates Cohort).
      Recruitment into PLACES was a 2-stage process: (1) random sample recruitment from
      the target population and completion of an initial intake survey and (2)
      completion of the first Annual Survey by pediatricians who responded positively
      to stage 1. Overall, 41.2% of pediatricians randomly selected to participate in
      PLACES indicated positive interest in the study by completing intake surveys; of
      this group, 1804 (93.7%) completed the first Annual Survey and were considered
      enrolled in PLACES. Participants were more likely to be female, AAP members, and
      graduates of US medical schools compared with the target sample; weights were
      calculated to adjust for these differences. We will survey PLACES pediatricians 2
      times per year. PLACES data will allow the AAP to examine career and life choices
      and transitions experienced by early-career pediatricians. 

PMID- 26216331
TI  - Immunogenicity, Safety, and Tolerability of a Hexavalent Vaccine in Infants.
AB  - BACKGROUND: DTaP5-IPV-Hib-HepB is a fully liquid investigational hexavalent
      vaccine directed against 6 diseases. METHODS: This multicenter, open-label,
      comparator-controlled, phase III study randomly assigned healthy infants 2-to-1
      as follows: group 1 received DTaP5-IPV-Hib-HepB, PCV13, and RV5 at 2, 4, and 6
      months of age followed by DTaP5, Hib-OMP, and PCV13 at 15 months of age; group 2
      received DTaP5-IPV/Hib, PCV13, and RV5 at 2, 4, and 6 months of age, with HepB at
      2 and 6 months of age, followed by DTaP5, Hib-TT, and PCV13 at 15 months of age.
      RESULTS: Overall, 981 participants were vaccinated in group 1 and 484 in group 2.
      Immune responses in group 1 to all antigens contained in DTaP5-IPV-Hib-HepB 1
      month after dose 3 and for concomitant rotavirus vaccine were noninferior to
      those in group 2, with the exception of antipertussis filamentous hemagglutinin
      (FHA) geometric mean concentrations (GMCs). Vaccine response rates for FHA were
      noninferior to control. After the toddler dose, group 1 immune responses were
      noninferior to group 2 for all pertussis antigens. Solicited adverse event rates
      after any dose were similar in both groups, with the exceptions of increased
      injection-site erythema, increased fever, and decreased appetite in group 1.
      Fever was not associated with hospitalization or seizures. CONCLUSIONS: The
      safety and immunogenicity of DTaP5-IPV-Hib-HepB are comparable with the analogous
      licensed component vaccines. Decreased FHA GMCs and increased injection-site
      reactions and fever are unlikely to be clinically significant. DTaP5-IPV-Hib-HepB
      provides a new combination vaccine option aligned with the recommended US infant
      immunization schedule.

PMID- 26216332
TI  - Validation of a Prediction Tool for Abusive Head Trauma.
AB  - BACKGROUND AND OBJECTIVES: Abusive head trauma (AHT) may be missed in the
      clinical setting. Clinical prediction tools are used to reduce variability in
      practice and inform decision-making. From a systematic review and individual
      patient data analysis we derived the Predicting Abusive Head Trauma (PredAHT)
      tool, using multilevel logistic regression to predict likelihood of AHT. This
      study aims to externally validate the PredAHT tool. METHODS: Consecutive children
      aged <36 months admitted with an intracranial injury, confirmed as abusive or
      nonabusive, to 2 sites used in the original model were ascertained. Details of 6
      influential features were recorded (retinal hemorrhage, rib and long -bone
      fractures, apnea, seizures, and head or neck bruising). We estimated the
      likelihood of an unrecorded feature being present with multiple imputation;
      analysis included sensitivity, specificity, and area under the curve, with 95%
      confidence intervals (CIs). RESULTS: Data included 133 non-AHT cases and 65 AHT
      cases, 97% of children were <24 months old. Consistent with original predictions,
      when >=3 features were present in a child <36 months old with intracranial
      injury, the estimated probability of AHT was >81.5% (95% CI, 63.3-91.8). The
      sensitivity of the tool was 72.3% (95% CI, 60.4-81.7), the specificity was 85.7%
      (95% CI, 78.8-90.7), area under the curve 0.88 (95% CI, 0.823-0.926).
      CONCLUSIONS: When tested on novel data, the PredAHT tool performed well. This
      tool has the potential to contribute to decision-making in these challenging
      cases. An implementation study is needed to explore its performance and utility
      within the child protection process.

PMID- 26216333
TI  - Mosaic Tetrasomy 9p: A Mendelian Condition Associated With Pediatric-Onset
      Overlap Myositis.
AB  - Pediatric-onset inflammatory myositis (IM) and systemic lupus erythematosus (SLE)
      are rare inflammatory diseases. Both result from the complex interaction of
      genetic and environmental factors. An increasing number of Mendelian conditions
      predisposing to the development of SLE have been recently identified. These
      include monogenic conditions, referred to as the type I interferonopathies,
      associated with a primary upregulation of type I interferon (IFN), a key cytokine
      in the pathogenesis of SLE and some cases of IM. Here, we report on a pediatric
      onset inflammatory overlap phenotype in a 6-year-old girl who was shown to carry
      mosaic tetrasomy 9p. The patient presented with myositis overlapping with
      lupuslike features. Myositis was characterized by a proximal muscular weakness
      and HLA class I antigen myofiber overexpression on muscle biopsy. Lupus-like
      manifestations consisted of pericarditis, pleuritis, and positive antinuclear and
      anti-SSA (Sjogren-syndrome A) antibodies. Complete remission was achieved with
      corticosteroids and mycophenolate mofetyl. Analysis of tetrasomy 9p showed mosaic
      tetrasomy in the 9p24.3q12 region, including the type I IFN cluster, and
      increased expression of IFN-stimulated genes. These data suggest that mosaic
      tetrasomy 9p can be associated with an upregulation of type I IFN signaling,
      predisposing to inflammatory myositis and lupus-like features. Thus, unexplained
      muscle or other organ involvement in patients carrying mosaic tetrasomy of the
      type IFN cluster of chromosome 9p should lead to the search for IM and/or
      lupuslike disease, and karyotype should be performed in patients with SLE or IM
      with mental retardation. 

PMID- 26216334
TI  - C-F sp(2) bond functionalization mediated by niobium complexes.
AB  - Insertion chemistry of isocyanide molecules was used to functionalize C-F sp(2)
      bonds after their oxidative addition across the metal center in a beta
      diketiminate niobium(iii) imido complex (BDI)Nb(N(t)Bu)(C6H6). The complexes
      formed, 3a-b ([BDI]Nb(PhC[double bond, length as m-dash]N)(N(t)Bu)(F) (R = 1,6
      diisopropylphenyl, tert-butyl), were characterized by NMR spectroscopy and X-ray
      analysis. Further treatment with phenylsilane induced H/F exchange under mild
      conditions, which was followed by hydride transfer to the inserted isocyanide.
      Divergent reactivity was observed when the two analogous aryl and tert-butyl
      isocyanide insertion products were treated with phenylsilane. 

PMID- 26216335
TI  - Cyclotrimerization-Induced Chiral Supramolecular Structures of 4
      Ethynyltriphenylamine on Au(111) Surface.
AB  - Cyclotrimerization-induced chiral supramolecular structures of 4
      ethynyltriphenylamine (ETPA) have been synthesized on the Au(111) surface through
      alkyne-based reactions. Whereas the ETPA molecules adsorbed on the Au(111)
      surface remain inert and form a close-packed self-assembled structure at room
      temperature, the combination of scanning tunneling microscopy observations and
      theoretical calculations unambiguously reveal that the ETPA molecules
      cyclotrimerize to form new trimer-like species-1,3,5-tris[4
      (diphenylamino)phenyl]benzene (TPAPB)-after annealing at 323 K. Further annealing
      drives these cyclotrimerized TPAPB molecules to form chiral hexagonal
      supramolecular structures with an extraordinary self-healing ability. 

PMID- 26216336
TI  - FeV2S4 as a high capacity electrode material for sodium-ion batteries.
AB  - Iron vanadium sulfide (FeV2S4) was synthesized via a high temperature solid state
      reaction and was investigated as a cheap anode material for Na and Li ion
      batteries. Discharge capacities as high as 723 mA h g(-1) (Na) and 890 mA h g(-1)
      (Li) were found for half-cell measurements at room temperature. The capacity of
      the Na-FeV2S4 system remained constant at 529 mA h g(-1) after the 10th cycle
      with an area capacity of 2.7 mA h cm(-2) being very close to that of conventional
      Li-ion technology. 

PMID- 26216338
TI  - Rehabilitation of a Completely Edentulous Patient with Nonreducible Bilateral
      Anterior Dislocation of the Temporomandibular Joint: A Prosthodontic Challenge
      Clinical Report.
AB  - Nonreduced bilateral anterior dislocation of the temporomandibular joint (TMJ) is
      an extremely rare condition, and its prosthodontic rehabilitation is a clinical
      challenge, especially in patients who refuse to or cannot undergo surgery. There
      are no previous clinical reports of successful or standardized prosthetic
      rehabilitation approaches for patients with this condition. This clinical report
      describes the successful prosthodontic management of an edentulous patient with
      nonreduced bilateral anterior dislocation of the TMJ. 

PMID- 26216339
TI  - Narrow band imaging in the intra-operative definition of resection margins in
      oral cavity and oropharyngeal cancer.
AB  - OBJECTIVES: In oncological surgery, a three-dimensional resection 1.5-2 cm from
      the gross tumour edge is currently considered appropriate, and the status of
      resection margins is the most reliable indicator of radicality. Awareness of
      "field cancerization" calls for a re-evaluation of the benchmarks of tumour
      resection; however, its identification is not simple because the dysplastic areas
      may be far from the main lesion and difficult to recognize macroscopically. New
      technologies such as narrow band imaging (NBI) could improve the detection of
      neoplastic and pre-neoplastic areas, ensuring more precise resections. The main
      purpose of this study was to investigate the value of NBI in detecting pre
      cancerous areas and/or cancer around the tumour bulk intra-operatively, to
      achieve adequate resection of the tumour. MATERIALS AND METHODS: The resection
      margins of 8 oral cavity and 8 oropharyngeal cancers were first drawn by
      macroscopic evaluation and then re-defined using NBI. Resections were performed
      following the NBI-drawing if extemporaneous histological examinations of the NBI
      defined enlargements were positive for dysplasia or cancer. The number of clear
      margins was evaluated. RESULTS: Resections margins were free of tumour or
      dysplasia at extemporaneous examination; on definitive histology, two patients
      had a margin positive for cancer and dysplasia, respectively. Among the NBI
      defined enlargements, 25% were positive for dysplasia and 75% for cancer. The
      sensitivity, specificity, positive and negative predictive values were 100%,
      88.9%, 100% and 87.5%, respectively. CONCLUSION: The method we propose could be
      useful for obtaining free surgical margins and reducing the potential development
      of tumour foci resulting from incomplete resection.

PMID- 26216337
TI  - Odintifier--A computational method for identifying insertions of organellar
      origin from modern and ancient high-throughput sequencing data based on haplotype
      phasing.
AB  - BACKGROUND: Cellular organelles with genomes of their own (e.g. plastids and
      mitochondria) can pass genetic sequences to other organellar genomes within the
      cell in many species across the eukaryote phylogeny. The extent of the occurrence
      of these organellar-derived inserted sequences (odins) is still unknown, but if
      not accounted for in genomic and phylogenetic studies, they can be a source of
      error. However, if correctly identified, these inserted sequences can be used for
      evolutionary and comparative genomic studies. Although such insertions can be
      detected using various laboratory and bioinformatic strategies, there is
      currently no straightforward way to apply them as a standard organellar genome
      assembly on next-generation sequencing data. Furthermore, most current methods
      for identification of such insertions are unsuitable for use on non-model
      organisms or ancient DNA datasets. RESULTS: We present a bioinformatic method
      that uses phasing algorithms to reconstruct both source and inserted organelle
      sequences. The method was tested in different shotgun and organellar-enriched DNA
      high-throughput sequencing (HTS) datasets from ancient and modern samples.
      Specifically, we used datasets from lions (Panthera leo ssp. and Panthera leo
      leo) to characterize insertions from mitochondrial origin, and from common
      grapevine (Vitis vinifera) and bugle (Ajuga reptans) to characterize insertions
      derived from plastid genomes. Comparison of the results against other available
      organelle genome assembly methods demonstrated that our new method provides an
      improvement in the sequence assembly. CONCLUSION: Using datasets from a wide
      range of species and different levels of complexity we showed that our novel
      bioinformatic method based on phasing algorithms can be used to achieve the next
      two goals: i) reference-guided assembly of chloroplast/mitochondrial genomes from
      HTS data and ii) identification and simultaneous assembly of odins. This method
      represents the first application of haplotype phasing for automatic detection of
      odins and reference-based organellar genome assembly.

PMID- 26216340
TI  - The epidemiology of head and neck squamous cell carcinoma in The Netherlands
      during the era of HPV-related oropharyngeal squamous cell carcinoma. Is there
      really evidence for a change?
AB  - BACKGROUND: Several recent studies have shown that incidence of oropharyngeal
      carcinomas is rising in the Western World. This increase has been attributed to
      changes in the etiology of oropharyngeal carcinomas with a growing role for
      infections with Human Papilloma viruses. This nationwide study evaluates and
      compares trends in incidence, clinical behavior and tumor characteristics of
      oropharyngeal and oral squamous cell cancer. METHODS: This study comprised all
      16,480 patients with primary squamous cell carcinoma of the oral tongue (OTSCC),
      oral cavity excluding oral tongue (OCSCC), and oropharynx (OPSCC) diagnosed from
      1989 through 2008 in The Netherlands. We assessed trends in age-standardized
      incidence, second cancer risk and subsite specific relative survival (RS) over
      time. RESULTS: Incidence of OTSCC and OPSCC in males and incidence of all
      subsites in females increased significantly from 1989 through 2008. In males
      increases in incidence were largely restricted to the 50-64 year age group
      (estimated annual percentage change 2.2% and 3.2% for OTSCC and OPSCC,
      respectively), while in females incidence increased for most age groups. The
      incidence of OCSCC (excl. oral tongue) and OPSCC before 50 years of age
      decreased. Patients with OPSCC showed the poorest prognosis with a relative
      survival of 41.6% after 5 years and 29.4% after 10 years (P<0.001) over the
      entire period 1989-2008. However survival increased substantially for OPSCC
      patients over time (5-year RS of 37.2% in 1989-1993 to 47.6% in 2004-2008,
      P<0.001). CONCLUSION: Although incidence of OPSCC did increase since 1989,
      especially in females, similar increases were seen for OCSCC (excl. oral tongue)
      and OTSCC. Our study does not appear to support that HPV is the main contributor
      to a rising incidence of OPSCC as the effects of changes in smoking and alcohol
      use cannot be discounted.

PMID- 26216341
TI  - Traumatic retinal detachment--the difficulty and importance of correct diagnosis.
AB  - Accurate characterization of a retinal detachment as traumatic is often
      difficult, but is important because it may instigate a careful search for occult
      coexistent traumatic pathology, affect the prognosis and the treatment of both
      eyes, influence insurance coverage benefits and medical-legal determinations, and
      is essential for epidemiologic studies. We review the epidemiology and
      pathophysiology of traumatic retinal detachment, common obstacles to correct
      diagnosis, diagnostic guidelines, and outline categories of traumatic causal
      relationships. Because there is no generally accepted definition of traumatic
      retinal detachment, we offer a practical one. Categorization as traumatic should
      be based on the particular history and physical examination rather than
      epidemiologic criteria. 

PMID- 26216342
TI  - Scrotal ultrasound findings in previously congenital and acquired unilateral
      undescended testes and their contralateral normally descended testis.
AB  - The aim of this study was to report on different anomalies found by physical
      examination and scrotal ultrasound in men with previously unilateral congenital
      undescended testes (UDT; N = 50), acquired UDT (N = 49), their contralateral
      normally descended testis (CNDT) and control testes (N = 53). Acquired UDT
      significantly more often had a testicular volume being <15 mL than congenital UDT
      (88% vs. 68%). In the congenital group, significant differences were found
      between UDT and CNDT for soft consistency (UDT 36% vs. CNDT 14%), epididymal
      diameter (UDT 7.6 mm vs. CNDT 8.9 mm), testicular volume (UDT 9.8 mL vs. CNDT
      13.8 mL), and inhomogeneous parenchyma (UDT 38% vs. CNDT 14%). In the acquired
      group, significant differences were found between UDT and CNDT for epididymal
      diameter (UDT 7.5 mm vs. CNDT 8 mm), testicular volume (UDT 9.3 mL vs. CNDT 14.1
      mL), testicular volume <15 mL (UDT 88% vs. CNDT 59%), and inhomogeneous
      parenchyma (UDT 27% vs. CNDT 6%). The following parameters of congenital UDT,
      acquired UDT, congenital CNDT, and/or acquired CNDT significantly differed
      compared with controls: soft testicular consistency (congenital UDT 36%, acquired
      UDT 20%, congenital CNDT 14%, acquired CNDT 12% vs. controls 0%), epididymal
      diameter (congenital UDT 7.6 mm, acquired UDT 7.5 mm, acquired CNDT 8 mm vs.
      controls 9.2 mm), testicular volume (congenital UDT 9.8 mL, acquired UDT 9.3 mL,
      congenital CNDT 13.8 mL, acquired CNDT 14.1 mL vs. control testes 15.8 mL),
      testicular volume <15 mL (congenital UDT 68%, acquired UDT 88%, congenital CNDT
      66% vs. controls 43%), inhomogeneous parenchyma (congenital UDT 38%, acquired UDT
      27%, congenital CNDT 14% vs. controls 0%), and testicular microlithiasis
      (congenital CNDT 24% vs. control testes 8%). Few differences between congenital
      and acquired unilateral UDT and congenital and acquired CNDT support the
      hypothesis of a spectrum of maldescended testes containing congenital and
      acquired UDT instead of them being two different entities. The CNDT also has
      anomalies albeit less severe than the UDT, indicating that in unilateral UDT both
      testes are affected. 

PMID- 26216344
TI  - Lethal photosensitisation of Prevotellaceae under anaerobic conditions by their
      endogenous porphyrins.
AB  - BACKGROUND: Oxygen is generally considered essential for lethal
      photosensitisation by photodynamic processes. The oral anaerobes, Prevotella
      intermedia and P. nigrescens are known to be photosensitive, but are also
      extremely sensitive to the cytotoxic effects of oxygen. METHODS: The
      Prevotellaceae were exposed to two 405 nm light sources for different exposure
      times in an anaerobic chamber. Viable counts of the light exposed samples were
      compared to light-free controls to determine the proportion of bacteria killed.
      RESULTS: Lethal photosensitivity was demonstrated against P. intermedia and P.
      nigrescens. The proportions of bacteria killed by either the light-emitting diode
      or laser pointer were similar at a given energy density (J/cm(2)). CONCLUSIONS:
      Lethal photosensitivity was demonstrated in two species of Prevotella under
      anaerobic conditions.

PMID- 26216345
TI  - Driving behaviour in adults with attention deficit/hyperactivity disorder.
AB  - BACKGROUND: Little is known about the impact of cognitive impairments on driving
      in adults with ADHD. The present study compared the performance of adults with
      and without ADHD in a driving simulator on two different routes: an urban route
      which we hypothesised would exacerbate weak impulse control in ADHD and a
      motorway route, to challenge deficits in sustained attention. METHODS: Adults
      with (n = 22, 16 males) and without (n = 21, 18 males) ADHD completed a simulated
      driving session while eye movement data were recorded simultaneously.
      Participants also completed the Manchester Driving Behaviour Questionnaire (DBQ)
      and the Conners Adult ADHD Rating Scale (CAARS). Measures of driving performance
      included average speed, proportion distance travelled over speed limit (speeding)
      and lane deviation. These variables and the eye movement measures (spread of
      fixations, mean fixation duration) were compared between groups and routes. Also,
      driving behaviours, including responses to programmed events, were categorised
      and the frequencies within categories were compared between groups. Finally,
      speech analysis was performed to compare emotional verbal expressions during
      driving between groups. RESULTS: ADHD participants reported significantly more
      Violations and Lapses on the DBQ than control participants and significantly more
      accidents. Average speed and speeding were also higher but did not interact with
      route type. ADHD participants showed poorer vehicle control, greater levels of
      frustration with other road users (including greater frequencies of negative
      comments) and a trend for less safe driving when changing lanes/overtaking on the
      motorway. These effects were predicted by hyperactive/impulsive CAARS scores.
      They were also more likely to cause a crash/near miss when an event occurred on
      the urban route. CONCLUSIONS: The results suggest that difficulty regulating and
      controlling impulsive behavior, reflected in speeding, frustration with other
      road users, less safety when changing lanes on the motorway and a greater
      likelihood of an accident following an unexpected event, underlie impaired
      driving in ADHD. Hyperactivity/impulsivity symptoms correlated with these
      indices. Deficits in sustained attention seemed to play a lesser role in this
      particular study, although further research is needed to determine whether
      effects on attention emerge over longer periods of time and/or are influenced by
      the novelty of the simulator environment.

PMID- 26216346
TI  - Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability
      facial anomalies syndrome.
AB  - The life-threatening Immunodeficiency, Centromeric Instability and Facial
      Anomalies (ICF) syndrome is a genetically heterogeneous autosomal recessive
      disorder. Twenty percent of patients cannot be explained by mutations in the
      known ICF genes DNA methyltransferase 3B or zinc-finger and BTB domain containing
      24. Here we report mutations in the cell division cycle associated 7 and the
      helicase, lymphoid-specific genes in 10 unexplained ICF cases. Our data highlight
      the genetic heterogeneity of ICF syndrome; however, they provide evidence that
      all genes act in common or converging pathways leading to the ICF phenotype. 

PMID- 26216347
TI  - Predictors and patterns of recurrence after curative liver resection in
      intrahepatic cholangiocarcinoma, for application of postoperative radiotherapy: a
      retrospective study.
AB  - BACKGROUND: The majority of patients with intrahepatic cholangiocarcinoma (IHCC)
      who undergo complete tumor resection subsequently develop tumor recurrence. The
      objectives of this study were to determine the risk factors for IHCC recurrence
      after curative (R0) liver resection and to identify the feasibility about
      postoperative adjuvant radiation therapy (RT). METHODS: We retrospectively
      reviewed patients who underwent liver resection for IHCC between April 1995 and
      December 2012 at Samsung Medical Center. Cox regression analysis was performed to
      determine risk factors of recurrence. Patients with a recurrence in remnant liver
      within 2 cm from the resection margin, with or without locoregional lymph node
      (LN) metastases, were considered as potential RT candidates. Center-of-mass (COM)
      distances between the recurrent cancers and the cut surface were measured with
      MATLAB. RESULTS: We included 153 out of 198 patients who underwent partial liver
      resection for IHCC. About two thirds (n=93, 60.8%) of patients developed
      recurrent disease. The median recurrence-free survival (RFS) was 14 months
      (range, 0-204). Tumor size>=4.0 cm, LN metastasis and multiple tumors were
      significant predictors of IHCC recurrence on multivariate analysis. Tumor
      size>=5.0 cm was the only factor associated with recurrence beyond the RT field
      in patients with recurrence. Among 93 patients with recurrence, 16 (17.2%)
      patients were recurred in the RT field. CONCLUSION: After curative resection in
      IHCC, more than 60% of patients recurred, and among recurred patients, 17.2% were
      recurred within the RT field. Consequently, for control of locoregional
      recurrence, adjuvant RT could be carefully considered in patients with recurrence
      factors. Especially, patients with a tumor size larger than 5 cm should be
      judiciously selected for adjuvant RT.

PMID- 26216348
TI  - Is there any link between joint hypermobility and mitral valve prolapse in
      patients with fibromyalgia syndrome?
AB  - The objective of the present study is to determine whether benign joint
      hypermobility syndrome (BJHS) modifies the risk of mitral valve prolapse (MVP) in
      patients with fibromyalgia (FM). Female patients fulfilling the 1990 American
      College of Rheumatology (ACR) diagnostic criteria for FM were included into the
      study. Joint hypermobility and BJHS were assessed using Beighton's scoring system
      and Brighton criteria, respectively. Echocardiograpic evaluation was performed in
      order to test the presence of MVP. Of the 75 female FM patients, 68.0 % (n = 51)
      and 20.0 % (n = 15) were diagnosed with BJHS and MVP, respectively. The
      frequencies of both MVP and BJHS seemed higher than the general population
      prevalence (p = 0.000 for both). The frequency of MVP was significantly higher in
      patients with BJHS than that in patients without BJHS (p = 0.028). In addition,
      BJHS was found to increase the risk of MVP approximately ninefold [odds ratio
      (OR) 8.7, 95 % confidence interval (CI) 1.1-70.7]. As a result, BJHS and MVP are
      both common in female patients with FM. Moreover, among the female patients with
      FM, those with BJHS are about nine times more prone to MVP than those without
      BJHS. Cardiologic assessment might be added to the routine follow-up strategies
      in FM patients with BJHS in order to exclude the cardiac pathologies, especially
      MVP. 

PMID- 26216349
TI  - The quality of clinical practice guidelines in traditional medicine in Korea:
      appraisal using the AGREE II instrument.
AB  - BACKGROUND: This study aimed to evaluate the quality of the current clinical
      practice guidelines (CPGs) in traditional medicine (TM) in South Korea using the
      Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument to
      further enhance the CPG development. METHODS: A search was performed for
      guidelines in Korea from inception until March 2014 in the major Korean guideline
      websites [the Korean Medical Guideline Information Centre (KoMGI), the Korean
      Guideline Clearing House (KGC)], PubMed and seven Korean electronic databases;
      the Association of Korean Oriental Medicine (AKOM) was also consulted. Five
      independent assessors rated the quality of each CPG using the AGREE II instrument
      and calculated the mean score of each AGREE item. The overall agreement amongst
      reviewers was evaluated using the intra-class correlation coefficient (ICC).
      RESULTS: Initially, 17 CPGs were examined for TM in Korea, and only 8 CPGs
      satisfied the inclusion criteria. The mean scores for each AGREE II domain were
      as follows: (1) scope and purpose, 60.0 % (CIs, 45.05-74.94 %); (2) stakeholder
      involvement, 56.11 % (41.28-70.94 %); (3) rigour of development, 42.7 % (23.48
      61.92 %); (4) clarity and presentation, 62.50 % (50.89-74.10 %); (5)
      applicability, 20.31 % (13.96-26.66 %); and (6) editorial independence, 44.58 %
      (10.78-78.38 %). All of the CPGs were rated as "recommended with provisos or
      modifications". The ICC values for CPG appraisal using the AGREE II ranged from
      0.230 to 0.993. CONCLUSIONS: To improve clinical practice and health outcomes,
      well-developed CPGs are needed. The quality of CPGs for TM in Korea has remained
      suboptimal according to the AGREE II instrument evaluation. Therefore, guideline
      developers in Korea should make more of an effort to ensure high-quality CPGs.

PMID- 26216350
TI  - MicroRNAs in Ovarian Cancer.
AB  - Ovarian cancer, consisting predominantly of ovarian carcinoma, is the eighth most
      common cancer in women and the most lethal gynecologic malignancy. Efforts focus
      on identifying biomarkers which may aid in early diagnosis and reduce mortality,
      as well as on characterizing therapeutic targets with the aim of circumventing
      chemoresistance and prolonging survival at advanced-stage disease. MicroRNAs
      (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene
      expression, and have been found to play an important role in ovarian carcinoma.
      Recent research has identified multiple miRNAs involved in the biology and
      progression of the disease, and supports a role for miRNAs as potential
      biomarkers, predictive markers and prognostic factors. Many of the studies
      published to date nevertheless suffer from critical weaknesses which affect data
      quality and reproducibility, including the comparison of normal ovaries to tumor
      tissue without compensation for the highly discrepant target cell fraction in
      these two specimen types and the inclusion of carcinomas of different histotypes,
      non-epithelial tumors or tumors of non-specified histology. These shortcomings
      highlight the critical role of pathologists as part of the team in the setting of
      such research. This review summarizes current knowledge in this area and
      discusses the potential clinical relevance of miRNAs in ovarian carcinoma, with
      focus on studies of clinical specimens in which tissue selection has been deemed
      adequate. 

PMID- 26216351
TI  - Spread of pathology in amyotrophic lateral sclerosis: assessment of
      phosphorylated TDP-43 along axonal pathways.
AB  - INTRODUCTION: The progression of amyotrophic lateral sclerosis (ALS) through the
      brain has recently been staged using independent neuropathological and
      neuroimaging modalities. The two schemes tie into the concept of pathological
      spread through corticofugal axonal transmission that stems from observation of
      oligodendrocyte pTDP-43 aggregates along with neuronal inclusions. Here, we aimed
      to assess evidence of transmission along axonal pathways by looking for pTDP-43
      oligodendrocyte pathology in involved white matter tracts, and to present a first
      validation of the neuropathological staging scheme. pTDP-43 immunohistochemistry
      was performed in select white matter tracts and grey matter regions from the
      staging scheme in postmortem-confirmed ALS cases (N = 34). Double-labelling
      immunofluorescence was performed to confirm co-localisation of pTDP-43
      immunoreactivity to oligodendrocytes. RESULTS: While pTDP-43 immunoreactive
      oligodendrocytes were frequent in the white matter under the motor and sensory
      cortices, similar assessment of the white matter along the corticospinal tract
      and in the corpus callosum and cingulum bundle of the same cases revealed no pTDP
      43 pathology, questioning the involvement of oligodendrocytes in pathological
      propagation. The assessment of Betz cell loss revealed that the lack of deep
      white matter pTDP-43 oligodendrocyte pathology was not due to an absence of motor
      axons. Assessment of the propagation of pathology to different grey matter
      regions validated that all cases could be allocated to one of four
      neuropathological stages, although Stage 4 cases were found to differ
      significantly in age of onset (~10 years older) and disease duration (shorter
      duration than Stage 3 and similar to Stage 2). CONCLUSIONS: Four stages of ALS
      neuropathology can be consistently identified, although evidence of sequential
      clinical progression requires further assessment. As limited pTDP-43
      oligodendrocyte pathology in deep corticospinal and other white matter tracts
      from the motor cortex was observed, the propagation of pathology between neurons
      may not involve oligodendrocytes and the interpretation of the changes observed
      on neuroimaging should be modified accordingly.

PMID- 26216352
TI  - Reversal of Warburg Effect and Reactivation of Oxidative Phosphorylation by
      Differential Inhibition of EGFR Signaling Pathways in Non-Small Cell Lung Cancer.
AB  - PURPOSE: One of the hallmarks of cancer cells is the excessive conversion of
      glucose to lactate under normoxic conditions, also known as the Warburg effect.
      Here, we tested whether the targeted inhibition of EGFR may revert this effect
      and reactivate mitochondrial oxidative phosphorylation in non-small cell lung
      cancer (NSCLC). EXPERIMENTAL DESIGN: Sensitive (HCC827) and resistant (H1975 and
      H1993) NSCLC cells were treated with a panel of EGFR or MET inhibitors, and then
      tested for changes of EGFR signaling, glycolytic cascade, and mitochondrial
      function. Silencing of key glycolytic enzymes was then performed with targeted
      siRNAs. Furthermore, tumor-bearing nude mice treated with EGFR inhibitors were
      evaluated with (18)F-FDG PET/CT and tumors were analyzed for glycolytic and
      mitochondrial proteins. RESULTS: Effective inhibition of EGFR signaling in NSCLC
      cells induced a dramatic reduction of hexokinase II (HKII) and phospho-pyruvate
      kinase M2 (p-PKM2, Tyr105) levels as well as an upregulation of mitochondrial
      complexes subunits (OXPHOS). Accordingly, a decreased lactate secretion and
      increased intracellular ATP levels were also observed in response to EGFR
      inhibitors. Downregulation of HKII and PKM2 by targeted siRNA transfection did
      not cause upregulation of OXPHOS but enhanced the effects of EGFR TKIs.
      Conversely, selective inhibition of AKT and ERK1/2 caused OXPHOS upregulation and
      glycolysis inhibition, respectively. Similar findings were obtained in tumors
      from animals treated with appropriate EGFR inhibitors. CONCLUSIONS: Our findings
      indicate that EGFR inhibitors may reactivate oxidative phosphorylation of cancer
      cells and provide a mechanistic clue for the rational combination of agents
      targeting EGFR-dependent proliferation and glucose metabolism in cancer therapy.

PMID- 26216353
TI  - Re-evaluation of the species of hookworms infecting dogs in Central Vietnam.
AB  - BACKGROUND: Differentiation of canine hookworm species is crucial from both a
      veterinary and public health standpoint. In Vietnam, three hookworm species,
      namely Ancylostoma caninum, Ancylostoma braziliense and Uncinaria stenocephala
      are reported to infect dogs. In light of the emerging distribution of A.
      ceylanicum in Asia, this study aims to re-evaluate the status of Ancylostoma in
      dogs in Vietnam. METHODS: Faecal samples collected from 200 community dogs in Dak
      Lak province were subjected to faecal floatation for the detection of hookworm
      eggs. Hookworm-positive samples were subjected to a PCR-Restriction Fragment
      Length Polymorphism (PCR-RFLP) assay targeting the internal transcribed spacer
      (ITS) region of rDNA for hookworm species identification. A subset of hookworm
      positive samples was also subject to haplotype characterisation at the cytochrome
      oxidase-1 (COX-1) gene. Detailed morphological criteria were utilised in addition
      to molecular markers, to identify adult hookworms recovered from necropsied dogs.
      RESULTS: Of 200 canine faecal samples, 111 (55.5 %) were positive for hookworm
      eggs on faecal flotation. Of these, 94/111 (84.7 %) were successfully amplified
      and assigned species status by PCR-RFLP targeting the ITS region. In total, 54.3
      % (51/94) dogs harboured single infections with A. ceylanicum, 33.0 % (31/94)
      with A. caninum, and 12.7 % (12/94) harboured mixed infections with both A.
      ceylanicum and A. caninum. Adult worms recovered from necropsied dogs matched
      morphological description provided for A. ceylanicum, Looss (1911) for which the
      mediolateral and posteriolateral rays are parallel. Characterisation of the COX-1
      gene placed all Vietnamese canine isolates of A. ceylanicum within the 'zoonotic'
      haplotype. CONCLUSION: Based on this information, it is apparent that the
      hookworms present in dogs in Vietnam are those of A. ceylanicum and not A.
      braziliense. Owing to the endemic nature of this significant zoonosis in dogs,
      the study strongly advocates for specific identification of this hookworm in
      human hookworm surveys.

PMID- 26216354
TI  - Comparative human and rat neurospheres reveal species differences in chemical
      effects on neurodevelopmental key events.
AB  - The developing brain is highly vulnerable to the adverse effects of chemicals,
      resulting in neurodevelopmental disorders in humans. Currently, animal
      experiments in the rat are the gold standard for developmental neurotoxicity
      (DNT) testing; however, these guideline studies are insufficient in terms of
      animal use, time and costs and bear the issue of species extrapolation.
      Therefore, the necessity for alternative methods that predict DNT of chemicals
      faster, cheaper and with a high predictivity for humans is internationally agreed
      on. In this respect, we developed an in vitro model for DNT key event screening,
      which is based on primary human and rat neural progenitor cells grown as
      neurospheres. They are able to mimic basic processes of early fetal brain
      development and enable an investigation of species differences between humans and
      rodents in corresponding cellular models. The goal of this study was to
      investigate to what extent human and rat neurospheres were able to correctly
      predict the DNT potential of a well-characterized training set of nine chemicals
      by investigating effects on progenitor cell proliferation, migration and neuronal
      differentiation in parallel to cell viability, and to compare these chemical
      responses between human and rat neurospheres. We demonstrate that (1) by
      correlating these human and rat in vitro results to existing in vivo data, human
      and rat neurospheres classified most compounds correctly and thus may serve as a
      valuable component of a modular DNT testing strategy and (2) human and rat
      neurospheres differed in their sensitivity to most chemicals, reflecting
      toxicodynamic species differences of chemicals. 

PMID- 26216355
TI  - Prostate cancer: net survival and cause-specific survival rates after multiple
      imputation.
AB  - BACKGROUND: Estimations of survival rates are diverse and the choice of the
      appropriate method depends on the context. Given the increasing interest in
      multiple imputation methods, we explored the interest of a multiple imputation
      approach in the estimation of cause-specific survival, when a subset of causes of
      death was observed. METHODS: By using European Randomized Study of Screening for
      Prostate Cancer (ERSPC), 20 multiply imputed datasets were created and analyzed
      with a Multivariate Imputation by Chained Equation (MICE) algorithm. Then, cause
      specific survival was estimated on each dataset with two methods: Kaplan-Meier
      and competing risks. The two pooled cause-specific survival and confidence
      intervals were obtained using Rubin's rules after complementary log-log
      transformation. Net survival was estimated using Pohar-Perme's estimator and was
      compared to pooled cause-specific survival. Finally, a sensitivity analysis was
      performed to test the robustness of our constructed multiple imputation model.
      RESULTS: Cause-specific survival performed better than net survival, since this
      latter exceeded 100 % for almost the first 2 years of follow-up and after 9 years
      whereas the cause-specific survival decreased slowly and than stabilized at
      around 94 % at 9 years. Sensibility study results were satisfactory. CONCLUSIONS:
      On our basis of prostate cancer data, the results obtained by cause-specific
      survival after multiple imputation appeared to be better and more realistic than
      those obtained using net survival.

PMID- 26216356
TI  - The integrated disease surveillance and response system in northern Ghana:
      challenges to the core and support functions.
AB  - BACKGROUND: The integrated disease surveillance and response (IDSR) strategy was
      adopted in Ghana over a decade ago, yet gaps still remain in its proper
      functioning. The objective of this study was to assess the core and support
      functions of the IDSR system at the periphery level of the health system in
      northern Ghana. METHODS: A qualitative study has been conducted among 18 key
      informants in two districts of Upper East Region. The respondents were from 9
      health facilities considered representative of the health system (public, private
      and mission). A semi-structured questionnaire with focus on core and support
      functions (e.g. case detection, confirmation, reporting, analysis, investigation,
      response, training, supervision and resources) of the IDSR system was
      administered to the respondents. The responses were recorded according to
      specific themes. RESULTS: The majority (7/9) of health facilities had designated
      disease surveillance officers. Some informants were of the opinion that the core
      and support functions of the IDSR system had improved over time. In particular,
      mobile phone reporting was mentioned to have made IDSR report submission easier.
      However, none of the health facilities had copies of the IDSR Technical
      Guidelines for standard case definitions, laboratories were ill-equipped,
      supervision was largely absent and feedback occurred rather irregular. Informants
      also reported, that the community perceived diagnostic testing at the health
      facilities to be unreliable (e.g. tuberculosis, Human Immunodeficiency Virus). In
      addition, disease surveillance activities were of low priority for nurses,
      doctors, administrators and laboratory workers. CONCLUSIONS: Although the IDSR
      system was associated with some benefits to the system such as reporting and
      accessibility of surveillance reports, there remain major challenges to the
      functioning and the quality of IDSR in Ghana. Disease surveillance needs to be
      much strengthened in West Africa to cope with outbreaks such as the recent Ebola
      epidemic.

PMID- 26216357
TI  - One-year experience with an acute respiratory distress syndrome standard
      operating procedure on intensive care unit.
AB  - PURPOSE: Mortality in acute respiratory distress syndrome (ARDS) patients remains
      unacceptable high, and there is substantial variation in the diagnostic and
      management strategies used. We recently established a standardized algorithm for
      the early identification and guideline conform therapy of ARDS on intensive care
      units (ICUs). We here present the results of a first-year observatory period
      after implementation of the ARDS bundle on our ICU. METHODS AND RESULTS: A
      retrospective, observative, single-center case control study over a period of 4
      years was performed. We analyzed the effects after implementation of an ARDS
      standard operating procedure (SOP) on prevalence of the diagnosis ARDS, mortality
      from ARDS, and therapy strategies. Implementation of the SOP led to an increased
      frequency of ARDS diagnosis (P < .05), increased application of early prone
      positioning (P < .05), and use of neuromuscular blockers (P < .02) in ARDS
      patients. An influence on mortality in ARDS patients could not be detected after
      implementation of the SOP (P = not significant). CONCLUSION: A standardized ARDS
      bundle fundamentally increases awareness of this clinical picture on ICU and
      facilitates application of evidence-based therapies like prone positioning and
      use of neuromuscular blockers. These data encourage evaluating our ARDS SOP in a
      prospective trial to identify potential effects on mortality.

PMID- 26216358
TI  - Prevalence of bilateral Discoid Lateral Menisci (DLM) in patients operated for
      symptomatic DLM with a follow-up study on their asymptomatic contralateral knees:
      a Magnetic Resonance Imaging (MRI) assessment.
AB  - BACKGROUND: The purpose was to investigate prevalence of bilateral discoid
      lateral menisci (DLM) in Han Chinese patients who received surgery for
      symptomatic DLM, as well as a follow-up study of their asymptomatic contralateral
      knees using magnetic resonance imaging (MRI). METHODS: A total of 110 patients
      [50 males and 60 females; average age: 21.95 +/- 12.77 years (range: 6 to 67
      years)] admitted to our hospital with symptomatic DLM were treated with
      arthroscopic surgery. The contralateral asymptomatic knees were evaluated for DLM
      by MRI. Postoperative clinical evaluation was performed using the Lysholm knee
      scoring scale and International Knee Documentation Committee subjective knee
      evaluation. RESULTS: Eighty (72.73%) of 110 symptomatic DLM patients had
      bilateral DLM, of which 68 (85%) were of homotype (same type). Fourteen of 80
      bilateral DLM patients were symptomatic and received operations in both knees.
      Twelve of remaining 66 bilateral DLM patients with asymptomatic one knee
      underwent a second arthroscopic surgery as their asymptomatic knees became
      symptomatic over the five-year interim. Of these 12 cases, seven exhibited no
      shift and five showed posterocentral meniscal shift. Furthermore, at least two
      cases showed progression from asymptomatic grade II to symptomatic grade III over
      the interim. All patients showed significant improvement after surgery.
      CONCLUSIONS: The bilateral DLM rate of Han Chinese patients with symptomatic DLM
      was relatively high at 72.7 %, and 85 % of those were of homotype.

PMID- 26216359
TI  - Book me a room! (I have allergies and asthma).

PMID- 26216360
TI  - Total specific airway resistance vs spirometry in asthma evaluation in children
      in a large real-life population.
AB  - BACKGROUND: Total specific airway resistance (sRtot) has been introduced as an
      alternative technique to assess lung function with a particular application to
      younger children with asthma. OBJECTIVE: To establish a diagnostic value of the
      body plethysmographic parameter (sRtot) in asthma diagnosis in young children.
      METHODS: This was a prospective, noninterventional study. Children 4 to 18 year
      old with symptoms suggestive of asthma were included (n = 885). Subjects
      underwent body plethysmography and spirometry (when capable) with reversibility
      tests. Of 788 subjects who could perform spirometry in addition to body
      plethysmography, 578 were diagnosed with asthma. Subjects with asthma were
      treated for minimum of 6 months and then their asthma was confirmed or refuted.
      RESULTS: In 471 patients, asthma diagnosis was confirmed after 6 months of
      antiasthmatic treatment; 142 patients were 4 to 6 years old and 329 were 7 to 18
      years old. Change in response to bronchodilator in children with asthma was
      significant for sRtot (P = .02) but not for forced expiration volume in 1 second
      (P = .21); sRtot was more sensitive and specific in identifying children with
      reversible obstruction than spirometry. There was a significant association
      between sRtot and asthma diagnosis in patients 4 to 6 years old (odds ratio 1.02,
      95% confidence interval 1.01-1.03, P = .001); to differentiate subjects with
      asthma from those without asthma, the optimal cutoff point for sRtot was 174.5%.
      A sRtot value higher than 174.5% was associated with a positive prediction of an
      asthma diagnosis in patients 4 to 6 years old. A ratio of forced expiration
      volume in 1 second to forced vital capacity below 80% was not significantly
      associated with asthma. CONCLUSION: These data support the recommendation of
      performing sRtot rather than spirometry in young children as a fairly sensitive
      marker of asthma. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT01805635).

PMID- 26216361
TI  - Development of the Andalusian Registry of Patients Receiving Community Case
      Management, for the follow-up of people with complex chronic diseases.
AB  - RATIONALE, AIMS AND OBJECTIVES: Complex chronic diseases are a challenge for the
      current configuration of health services. Case management is a service frequently
      provided for people with chronic conditions, and despite its effectiveness in
      many outcomes, such as mortality or readmissions, uncertainty remains about the
      most effective form of team organization, structures and the nature of the
      interventions. Many processes and outcomes of case management for people with
      complex chronic conditions cannot be addressed with the information provided by
      electronic clinical records. Registries are frequently used to deal with this
      weakness. The aim of this study was to generate a registry-based information
      system of patients receiving case management to identify their clinical
      characteristics, their context of care, events identified during their follow-up,
      interventions developed by case managers and services used. METHODS: The study
      was divided into three phases, covering the detection of information needs, the
      design and its implementation in the health care system, using literature review
      and expert consensus methods to select variables that would be included in the
      registry. RESULTS: A total of 102 variables representing structure, processes and
      outcomes of case management were selected for their inclusion in the registry
      after the consensus phase. A web-based registry with modular and layered
      architecture was designed. The framework follows a pattern based on the model
      view-controller approach. In its first 6 months after the implementation, 102
      case managers have introduced an average number of 6.49 patients each one.
      CONCLUSIONS: The registry permits a complete and in-depth analysis of the
      characteristics of the patients who receive case management, the interventions
      delivered and some major outcomes as mortality, readmissions or adverse events.

PMID- 26216362
TI  - IgG4-related disease: case report and literature review.
AB  - IgG4-related disease (IgG4-RD) is relatively a new growing entity of immune
      mediated origin, characterized by a mass-forming lesion, the infiltration of IgG4
      positive plasma cells and occasionally elevated serum IgG4. It is considered to
      be both a systemic inflammation and sclerosing disease. The most common
      manifestations are parotid and lacrimal swelling, lymphadenopathy and autoimmune
      pancreatitis. Sclerosing cholangitis and retroperitoneal fibrosis are among the
      other mentioned frequent manifestations. The diagnosis should be approved histo
      pathologically but other conditions such as lymphoma should be carefully
      excluded. Patients with IgG4-RD respond beneficially to glucocorticoid therapy
      especially when given at early onset stages. In some cases, the combination of
      immunosuppressive agents is required. 

PMID- 26216363
TI  - The importance of antenatal diagnosis of congenital duodenal obstruction.
AB  - INTRODUCTION: The aim of this study was to compare the outcome of operated
      newborns that had an antenatal diagnosis of congenital duodenal obstruction (CDO)
      with those who had a late diagnosis in the postpartum period. MATERIALS AND
      METHODS: The newborns that were operated with the diagnosis of CDO in our
      department were retrospectively recorded. The patients were grouped according to
      the time of diagnosis; the ones who had an antenatal diagnosis were assigned to
      group 1, while the ones that had a diagnosis in the postpartum period were
      assigned to group 2. The groups were compared in terms of their pregnancy weeks
      at the time of birth, birth weight, additional congenital anomalies, the type of
      obstruction, the procedures that are applied, the day of operation, the time for
      oral feeding tolerance, the duration of hospital stay, and pre- and post
      operative complications. RESULTS: Fifteen patients with a diagnosis of CDO were
      operated on in our department between 2009 and 2014. Eight patients were male and
      seven patients were female. There were nine patients in group 1 and six patients
      in group 2. The diagnosis was confirmed in group 1 on the first day of the
      postpartum period. In the subanalysis, five patients had type 1 CDO and four had
      type 3 CDO in group 1, while five patients had type 1 CDO and one had type 3 CDO
      in group 2. There was not any complication in group 1 in the pre-operative
      period, but two patients had aspiration pneumonia and one had dehydration in
      group 2 pre-operatively. The mean operation day in the postpartum period was 2.34
      (+/-0.5) days in group 1 and 7.17 (+/-2.04) in group 2. The time for the patient
      to tolerate oral feeding in the post-operative period was 11.33 (+/-1.80) in
      group 1 and 14.83 (+/-2.48) in group 2. The duration of hospital stay in group 1
      was 20.67 (+/-9.81) days and 24.66 (+/-4.50) days in group 2. In the post
      operative period, chylous ascites occured in a patient in group 1 and the post
      operative period was complicated with ileus in one patient in group 2. No
      mortalities happened in both groups. CONCLUSION: The prenatal diagnosis of CDO
      affects the pre-operative complication rate, the time for the operation in the
      postpartum period, the duration to start post-operative oral feeding, and the
      duration of hospital stay, but does not affect the mortality or the morbidity.

PMID- 26216364
TI  - Association of infant and young child feeding practices with undernutrition in
      children: evidence from the Nepal Demographic and Health Survey.
AB  - BACKGROUND: Childhood undernutrition remains a highly influential risk factor in
      terms of the global burden of disease. Increasing evidence links infant and young
      child feeding (IYCF) practices to undernutrition. However, the results are
      inconsistent, and more country-specific studies are needed. OBJECTIVES: To
      determine the associations between IYCF practices and nutritional outcomes among
      children aged 0-23 months using a nationally representative dataset. METHODS: The
      study used data from the 2011 Nepal Demographic and Health Survey, and the data
      were analysed for children aged 0-23.9 months who had corresponding data for the
      outcome variables of interest (n = 890). Multiple linear and logistic regressions
      were undertaken and adjusted for the complex design of the survey, controlling
      for child, maternal, household and community characteristics. RESULTS: Of the 890
      children included in the study, 83% received age-appropriate breastfeeding but
      only 48% were breastfed within 1 hour of birth. Exclusive breastfeeding under 6
      months of age was associated with a higher weight-for-age Z-score (WAZ) and a
      lower probability of wasting, but the estimated effects were of borderline
      significance. A significant negative association was found between continued
      breastfeeding at 1 year and WAZ and weight-for-height Z-score (WHZ). Timely
      introduction of complementary feeding in children aged 6-8 months was associated
      with a higher WAZ [effect size (ES) 0.6, P < 0.01] and higher WHZ (ES 0.6, P <
      0.05). Higher dietary diversity index (DDI) was associated with higher height-for
      age Z-score (ES 0.1, P < 0.05 for each DDI point). Children who achieved minimum
      meal frequency had a higher WAZ (ES 0.3, P < 0.05). CONCLUSION: This is the first
      study to relate the wide ranges of IYCF indicators with child nutritional
      outcomes in Nepal, and it underscores the need to improve age-appropriate
      complementary feeding practices with a sustained focus on exclusive breastfeeding
      to reduce undernutrition in infants and young children.

PMID- 26216365
TI  - Adrenalectomy: a retroperitoneal procedure.

PMID- 26216366
TI  - Serum Cystatin C Levels are Positively Associated with Cardiovascular Autonomic
      Neuropathy in Patients with Type 2 Diabetes.
AB  - AIMS: Previous studies have reported that cystatin C is associated with
      degenerative disorder in the nervous system. However, the relationship between
      serum cystatin C concentrations and cardiovascular autonomic neuropathy (CAN) in
      patients with type 2 diabetes is currently unknown. The aim of this study was to
      assess the relationships between serum cystatin C levels and CAN in patients with
      type 2 diabetes. METHODS: A total of 357 patients with type 2 diabetes were
      studied in this cross-sectional study. CAN was diagnosed by a cardiovascular
      autonomic reflex test. According to the American Diabetes Association criteria,
      the degree of cardiovascular autonomic dysfunction was graded as normal, early,
      definite, or severe. CAN was either definite or severe in the subjects of the
      present study. RESULTS: Serum cystatin C concentrations were significantly higher
      in patients with CAN than in those without CAN. The mean cystatin C levels
      differed significantly according to the degree of cardiovascular autonomic
      dysfunction (normal, 0.78 mg/l; early, 0.79 mg/l; definite, 0.87 mg/l; severe,
      0.90 mg/l; P for trend=0.021) after adjustment for other covariates. In
      multivariate analysis, serum cystatin C levels were significantly associated with
      CAN (odds ratio [OR] of each standard deviation increase in the logarithmic
      value, 5.25; 95% confidence interval [CI], 1.17-23.70, P=0.025). CONCLUSIONS:
      Serum cystatin C levels are positively associated with CAN in patients with type
      2 diabetes.

PMID- 26216367
TI  - Effects of commonly used antidiabetic drugs on antioxidant enzymes and liver
      function test markers in type 2 diabetes mellitus subjects - pilot study.
AB  - OBJECTIVE: The present study analyzed the effects of antidiabetic drugs on
      antioxidant enzymes and liver function test (LFT) markers and their association
      with homeostatic model assessment of insulin resistance (HOMA-IR) in type 2
      diabetic subjects. METHODS: We assessed healthy and diabetic subjects (100 each).
      Diabetic subjects were divided based on treatment with only metformin, metformin
      in combination with other antidiabetic drugs and insulin in combination with
      other antidiabetic drugs. LFT markers, antioxidant status and HOMA-IR were
      assessed in the subjects. RESULTS: Superoxide dismutase activity was higher
      (p<0.01) while catalase activity was lower (p<0.01) in the diabetic subjects as
      compared to controls. Serum glutamate-pyruvate transaminase (SGPT) (p<0.01) and
      bilirubin (p<0.05) levels were higher in diabetic male subjects while urea
      (p<0.05) levels were lower and SGPT (p<0.01) levels were higher in diabetic
      female subjects. In male subjects consuming only metformin, a positive
      association between HOMA-IR and insulin (p<0.05) was seen. A positive association
      between HOMA-IR and glucose (p<0.01), insulin (p<0.01), SOD (p<0.01) and SGPT
      (p<0.05) was seen in males receiving metformin with other drugs. Interestingly,
      the female subjects on metformin displayed a positive association between HOMA-IR
      and insulin (p<0.05) only. A positive association of HOMA-IR with glucose
      (p<0.01) and insulin (p<0.05) was seen in females on metformin in combination
      with other anti-diabetic drugs. CONCLUSION: The alterations in the antioxidant
      enzyme activities and liver function tests are dependent upon the gender and
      glycemic status of subjects while the variations in correlations of HOMA-IR with
      antioxidant enzymes, liver function tests and inflammatory markers are dependent
      on type of treatments.

PMID- 26216368
TI  - The Impact of Thyroid Autoimmunity on the Clinical and Diabetes Parameters of
      Patients with Latent Autoimmune Diabetes in Adults.
AB  - AIM: We evaluated the clinical and diabetes parameters of latent autoimmune
      diabetes in adults (LADA) patients according to the presence of thyroid
      autoimmunity (TA). MATERIALS AND METHODS: Patients with LADA (diabetes onset
      after 30 years of age, no need for insulin treatment for at least 6 months after
      diabetes onset, positive for glutamic acid decarboxylase antibodies (GADA)) were
      evaluated for the presence of thyroid peroxidase antibodies (TPOAb) and were
      subjected to clinical and laboratory evaluations of the glycated hemoglobin and
      basal C peptide levels. The patients were stratified into either group A (with
      TA) or group B (without TA). RESULTS: We evaluated 104 (57 female and 47 male)
      patients with LADA. The mean age at diabetes onset was 44+/-10 years. The
      prevalence of TA among the LADA patients was 28.8% (30 patients; 23 female and 7
      male). In groups A and B, the mean age at diabetes onset was 41.47+/-10.15 and
      45.07+/-10 years (p=0.03), the basal C peptide level was 0.69+/-0.16 and 1.9+/
      1.3 ng/ml (p<0.0001), the glycated hemoglobin level was 9.8+/-2.2 and 9.1+/-2.2
      (p=0.04), and the time to insulin treatment was 3.2+/-2.1 years and 4.98+/-2.2
      years (p=0.038), respectively. The use of a basal bolus insulin regimen was more
      frequent in group A than in group B (56.7% and 35.1%, respectively; p=0.03).
      CONCLUSION: TA identifies a particular phenotype of LADA displaying a higher GADA
      titer, lower basal C peptide levels and poorer glycemic control.

PMID- 26216369
TI  - Low-grade Albuminuria Associated with Subclinical Left Ventricular Diastolic
      Dysfunction and Left Ventricular Remodeling.
AB  - AIMS: Low-grade albuminuria (LGA) has been shown to be associated with increased
      risk for cardiovascular disease. Our study investigated the relationship between
      normal urinary albumin-to-creatinine ratios (UACRs) and subclinical left
      ventricular (LV) diastolic dysfunction and remodeling in diabetics and non
      diabetics. METHODS: A total of 888 diabetic and 208 non-diabetic patients with
      normal UACRs (< 30 mg/g) from Fuzhou, Fujian Province, China were examined. The
      subjects were stratified into quartiles based on their respective UACR levels. LV
      diastolic function was defined by early diastolic transmitral velocities
      (E)/average early diastolic annular velocities (average e), accompanied by
      average e. LV remodeling was defined by LV mass indexed to body surface area and
      relative wall thickness based on 2-dimensional and Doppler echocardiography.
      RESULTS: UACR was independently associated with cardiac diastolic function as
      defined by E/e and average e (OR=1.042, P=0.001) and LV remodeling (OR=1.037,
      P=0.001) in all participants. Diabetic patients in the highest quartile of UACR
      demonstrated a greater risk of developing LV diastolic dysfunction by a magnitude
      of 1.625 (OR=1.625, P=0.037) than patients in the lowest quartile; those in the
      third and highest quartiles demonstrated a greater risk of LV remodeling by a
      magnitude of 1.729-1.994 compared to the lowest quartile (OR=1.729, P=0.027 and
      OR=1.994, P=0.005, respectively). The association between UACR and subclinical
      diastolic dysfunction was most prevalent in younger, non-obese, non-hypertensive
      females or patients who had experienced diabetes for fewer than 10 years. The
      association between UACR and LV remodeling was most prevalent in non-obese, older
      males, in patients with normal low-density lipoprotein levels, in patients who
      had experienced diabetes for fewer than 10 years, and in patients without
      hypertension. CONCLUSION: UACR was associated with subclinical LV diastolic
      dysfunction and remodeling in both patients with and without Type 2 diabetes. We
      conclude that LGA may also be a marker for subclinical cardiovascular damage in
      Type 2 diabetics.

PMID- 26216370
TI  - P wave analysis with wavelets identifies hypertensive patients at risk of
      recurrence of atrial fibrillation: A case-control study and 1year follow-up.
AB  - AIMS: Hypertension is a major risk factor for atrial fibrillation (AF); however,
      reliable non-invasive tools to assess AF risk in hypertensive patients are
      lacking. We sought to evaluate the efficacy of P wave wavelet analysis in
      predicting AF risk recurrence in a hypertensive cohort. METHODS: We studied 37
      hypertensive patients who presented with an AF episode for the first time and 37
      age- and sex-matched hypertensive controls without AF. P wave duration and energy
      variables were measured for each subject [i.e. mean and max P wave energy along
      horizontal (x), coronal (y) and sagittal (z) axes in low, intermediate and high
      frequency bands]. AF-free survival was assessed over a follow-up of 12.1+/
      0.4months. RESULTS: P wave duration (Pdurz) and mean P wave energy in the
      intermediate frequency band across sagittal axis (mean2z) were independently
      associated with baseline AF status (p=0.008 and p=0.001, respectively). Based on
      optimal cut-off points, four groups were formed: Pdurz<83.2ms/mean2z<6.2MUV(2)
      (n=23), Pdurz<83.2ms/mean2z>=6.2MUV(2) (n=10), Pdurz>=83.2ms/mean2z<6.2MUV(2)
      (n=22) and Pdurz>=83.2ms/mean2z>=6.2MUV(2) (n=19). AF-free survival decreased
      (Log Rank p<0.0001) from low risk (Pdurz<83.2ms/mean2z<6.2MUV(2)) to high-risk
      group (Pdurz>=83.2ms/mean2z>=6.2MUV(2)). Patients presenting with longer and
      higher energy P waves were at 18 times higher AF risk compared to those with
      neither (OR: 17.6, 95% CI: 3.7-84.3) even after adjustment for age, sex,
      hypertension duration, left atrial size, beta-blocker, ACEi/ARBs and statin
      therapy. CONCLUSIONS: P wave temporal and energy characteristics extracted using
      wavelet analysis can potentially serve as screening tool to identify hypertensive
      patients at risk of AF recurrence.

PMID- 26216371
TI  - The effects of right ventricular apical pacing with transvenous pacemaker and
      implantable cardioverter defibrillator on mitral and tricuspid regurgitation.
AB  - BACKGROUND: The incidence of new or worsening tricuspid regurgitation (TR) or
      mitral regurgitation (MR) after permanent pacemaker (PPM) or implantable
      cardioverter defibrillator (ICD) lead placement has not been well investigated.
      We studied the effect of transvenous leads implantation and right ventricular
      (RV) pacing on tricuspid and mitral valve regurgitations. METHODS: We reviewed
      the charts of all patients undergoing PPM or ICD lead placement in our
      electrophysiology laboratory from December 2001 to December 2006. RESULTS: A
      total of 206 patients (120 with PPM and 86 with ICD) had baseline
      echocardiography within 6months before, and a follow up study at least 6months
      after lead insertion. The mean age was 74+/-14years; 56% were men. The follow-up
      period was 29+/-19months. TR worsened by at least one grade after lead insertion
      in 44.7% patients (P<0.001). Pre- and post-implant changes in TR severity did not
      differ with respect to lead type (ICD vs. PPM) or degree of RV pacing dependence.
      As for MR; patients with high frequency of RV pacing (>40%) had a higher
      incidence of worsening MR when compared to those with low frequency of RV pacing
      (44% vs. 19%; P<0.001). CONCLUSION: PPM or ICD lead implantation worsens TR; that
      effect is probably induced by mechanical interferences with the TV closure and
      was consistent regardless the lead type or degree of RV Pacing. MR was noted to
      increase in patients with high frequency of RV pacing frequency; this is probably
      caused by the mechanical dyssynchrony induced by RV pacing.

PMID- 26216372
TI  - Nitrogen pools and flows during lab-scale degradation of old landfilled waste
      under different oxygen and water regimes.
AB  - Nitrogen emissions from municipal solid waste (MSW) landfills occur primarily via
      leachate, where they pose a long-term pollution problem in the form of ammonium.
      In-situ aeration was proposed as a remediation measure to mitigate nitrogenous
      landfill emissions, turning the anaerobic environment to anoxic and subsequently
      aerobic. As in-depth studies of the nitrogen cycle during landfill aeration had
      been largely missing, it was the aim of this work to establish a detailed
      nitrogen balance for aerobic and anaerobic degradation of landfilled MSW based on
      lab-scale experiments, and also investigating the effect of different water
      regimes on nitrogen transformation during aeration. Six landfill simulation
      reactors were operated in duplicate under different conditions: aerated wet (with
      water addition and recirculation), aerated dry (without water addition) and
      anaerobic (wet). The results showed that more than 78 % of the initial total
      nitrogen (TNinit) remained in the solids in all set ups, with the highest
      nitrogen losses achieved with water addition during aeration. In this case,
      gaseous nitrogen losses (as N2 due to denitrification) amounted up to 16.6 % of
      TNinit and around 4 % of TNinit was discharged via leachate. The aerated dry set
      up showed lower denitrification rates (2.6-8.8 % of TNinit was released as N2),
      but was associated with the highest N2O emissions (3.8-3.9 % of TNinit). For the
      anaerobic treatment the main pathway of nitrogen discharge was the leachate,
      where NH4 accounted for around 8 % of TNinit. These findings provide the basis
      for improved management strategies to enhance nitrogen removal during in-situ
      aeration of old landfills.

PMID- 26216373
TI  - Controlled canine retraction using orthodontic mini-implants coupled with
      bondable powerarms.
AB  - Many patients present with a substantial amount of anterior dental crowding,
      necessitating canine retraction prior to incisor alignment. Conventional
      biomechanics typically requires anchorage reinforcement and risks distal tipping
      of the canine crown and a delay before incisor alignment. However, it is now
      possible to produce controlled canine retraction without anchorage loss, even
      with narrow, flexible archwires in situ. This enables simultaneous alignment of
      displaced incisors. This technique involves a combination of orthodontic mini
      implants (OMIs) and a powerarm bonded directly on either the labial or palatal
      surface of the target tooth, as described in this paper. 

PMID- 26216374
TI  - The DYT1-interacting proteins bHLH010, bHLH089 and bHLH091 are redundantly
      required for Arabidopsis anther development and transcriptome.
AB  - The anther is the male reproductive organ of flowering plants, and the
      Arabidopsis bHLH transcription factors encoded by DYSFUNCTIONAL TAPETUM1 (DYT1)
      and ABORTED MICROSPORE (AMS) are required for control of the complex
      transcriptional networks regulating anther development. Knowledge of the
      mechanisms by which the bHLH proteins affect this diverse gene expression is
      quite limited. We examine here three recently duplicated Arabidopsis bHLH genes,
      bHLH010, bHLH089 and bHLH091, using evolutionary, genetic, morphological and
      transcriptomic approaches, and uncover their redundant functions in anther
      development. These three genes are relatively highly expressed in the tapetum of
      the Arabidopsis anther; single mutants at each of the bHLH010, bHLH089 and
      bHLH091 loci are developmentally normal, but the various double and triple
      combinations progressively exhibit increasingly defective anther phenotypes
      (abnormal tapetum morphology, delayed callose degeneration, and aborted pollen
      development), indicating their redundant functions in male fertility. Further
      transcriptomic and molecular analyses suggest that these three proteins act
      slightly later than DYT1, and also form protein complexes with DYT1, subsequently
      affecting the correct expression of many DYT1 target genes in the anther
      development transcriptional network. This study demonstrated that bHLH010,
      bHLH089 and bHLH091 together are important for the normal transcriptome of the
      developing Arabidopsis anther, possibly by forming a feed-forward loop with DYT1.

PMID- 26216375
TI  - Disorder and disconnection: parent experiences of liminality when caring for
      their dying child.
AB  - Parents caring for a child with a life threatening or life limiting illness
      experience a protracted and largely unknown journey, as they and their child
      oscillate somewhere between life and death. Using an interpretive qualitative
      approach, interviews were conducted with parents (n = 25) of children who had
      died. Findings reveal parents' experiences to be characterised by personal
      disorder and transformation as well as social marginalisation and disconnection.
      As such they confirm the validity of understanding these experiences as,
      fundamentally, one of liminality, in terms of both individual and collective
      response. In dissecting two inter-related dimensions of liminality, an underlying
      tension between how transition is subjectively experienced and how it is socially
      regulated is exposed. In particular, a structural failure to recognise the
      chronic nature of felt liminality can impede parents' effective transition.

PMID- 26216376
TI  - The role of MR-PET in abdominal and pelvic oncology.

PMID- 26216377
TI  - Orexins and fear: implications for the treatment of anxiety disorders.
AB  - An understanding of the neurobiological mechanisms involved in the regulation of
      fear is essential for the development of new treatments for anxiety disorders,
      such as phobias, panic, and post-traumatic stress disorders (PTSD). Orexins, also
      known as hypocretins, are neuropeptides located exclusively in hypothalamic
      neurons that have extensive projections throughout the central nervous system.
      Although this system was initially believed to be primarily involved in the
      regulation of feeding behavior, recent studies have shown that orexins also
      modulate neural circuits implicated in the expression and extinction of fear
      memories. Here, we discuss recent findings involving orexins in anxiety disorders
      and current clinical trials using orexin ligands that could be applied to
      identify new therapies for diseases characterized by pathological fear. 

PMID- 26216378
TI  - Nebulized fluticasone propionate, a viable alternative to systemic route in the
      management of childhood moderate asthma attack: A double-blind, double-dummy
      study.
AB  - BACKGROUND: In this study, we compared the clinical and immunological efficacy of
      nebulized corticosteroid (CS) to systemic route during treatment of moderate
      asthma attack in children. METHODS: In this randomized, placebo-controlled,
      double-blind, double-dummy, prospective study, 81 children aged 12 months to 16
      years experiencing asthma attack randomized into two treatment groups to receive,
      either; nebulized fluticasone propionate (n = 39, 2000 mcg/day) or oral
      methylprednisolone (n = 41, 1 mg/kg/day). Pulmonary index scores (PIS) were
      assessed at admission and at 1st, 4th, 8th, 12th, 24th, 48th hours, as well as,
      on day 7 and peak expiratory flow (PEF) at baseline and at the 7th day. Daily
      symptom and medication scores were recorded for all subjects. Immunological
      studies included phytohemagglutinin induced peripheral blood mononuclear cells
      culture supernatant for cytokine responses and CD4(+) CD25(+) FOXP3(+) T
      regulatory cell (T reg) percentage at baseline and day 7. RESULTS: The changes in
      PIS and PEF were similar in both treatment groups, with a significant improvement
      in both values at the 7th day, when compared to baseline. In both groups,
      significant reductions in symptom and medication scores were observed during the
      treatment period with no significant difference between the groups. At day 7 of
      intervention, phytohemagglutinin induced IL-4 level was significantly decreased
      only in the nebulized group compared to baseline (p = 0.01). Evaluation of
      cytokine responses by means of fold increase (stimulated (S)/unstimulated (US)
      ratio) revealed a significant reduction in IL-4, IL-5 and IL-17 only in nebulized
      group (p = 0.01, 0.01, 0.02; respectively). The fold increase value of IL-5 was
      significantly lower at 7th day in nebulized group when compared to systemic one
      (p = 0.02). At 7th day, although in both treatment groups the percentage of T reg
      cells was suppressed, it remained significantly higher in the nebule one when
      compared to systemic route (p = 0.04). CONCLUSION: In the management of moderate
      acute asthma attack, nebulized CS (2000 mcg daily) was found to be as effective
      as systemic route with regard to clinical improvement. In addition, immunological
      parameters were more in favor of nebulized route which may imply a salutary
      effect of local CS usage.

PMID- 26216379
TI  - Dual motor responses elicited by ethanol in the posterior VTA: Consequences of
      the blockade of MU-opioid receptors.
AB  - A recent hypothesis, based on electrophysiological and behavioural findings,
      suggests that ethanol simultaneously exerts opposed effects on the activity of
      dopamine (DA) neurons in the ventral tegmental area (VTA) through two parallel
      mechanisms, one promoting and the other reducing the GABA release onto VTA DA
      neurons. In this sense, the activating effects are mediated by salsolinol, a
      metabolite of ethanol, acting on the MU-opioid receptors (MORs) located in VTA
      GABA neurons. The inhibitory effects are, however, triggered by the non
      metabolized fraction of ethanol which would cause the GABAA receptors-mediated
      inhibition of VTA DA neurons. Since both trends tend to offset each other, only
      the use of appropriate pharmacological tools allows analysis of this phenomenon
      in depth. Herein, we present new behavioural findings supporting this hypothesis.
      Motor activity was evaluated in rats after intra-VTA administration of ethanol 35
      nmol, an apparently ineffective dose, 24 h after the irreversible blockade of
      MORs in the VTA with beta-FNA. Our results showed that this pre-treatment turned
      the initially ineffective ethanol dose into a depressant one, confirming that the
      activating effect of ethanol can be selectively suppressed without affecting the
      depressant effects mediated by the non-biotransformed fraction of ethanol. 

PMID- 26216380
TI  - Compassion: a critical review of peer-reviewed nursing literature.
AB  - AIMS AND OBJECTIVES: To provide a critical review of nursing literature about
      compassion, identifying major themes, questions arising and directions for future
      investigation of the topic. BACKGROUND: Compassion has emerged as a topic of
      broad social concern in recent years and is particularly pertinent to nurses.
      DESIGN: Critical review was selected as the most appropriate way of analysing
      literature from both qualitative research studies and conceptual articles.
      METHODS: An electronic database search was conducted, discovering articles
      published between 1952 and 2013. The search was then limited to publications
      since 2000 to capture recent development of the concept. The search was limited
      to peer-reviewed literature, excluding a large body of editorial material,
      resulting in 20 relevant articles. Two books were also added that contributed
      important perspective to the analysis. Critical analysis of the resulting
      material was undertaken to identify themes, tensions and implications in the
      literature. RESULTS: Major themes were compassion as practice and compassion as a
      moral virtue, holding implications for how nurses can demonstrate compassion in
      relation to contemporary healthcare values. A third major theme was the influence
      of institutional environments in facilitating or limiting the expression of
      compassion. CONCLUSIONS: Compassion is a human experience of deep significance to
      nursing and needs understanding in the context of healthcare environments
      dominated by discourses of efficiency and rationalisation. There is an emergent
      literature about how compassion may be understood, taught and sustained among
      nurses but it is a topic that requires continued attention. RELEVANCE TO CLINICAL
      PRACTICE: More precise understanding of compassion will support nurses in
      advocating for compassionate care, participating in interdisciplinary dialogue,
      and contributing to the design of healthcare environments that are conducive to
      compassionate care.

PMID- 26216381
TI  - Educational Experiences and Needs of Higher Education Students with Autism
      Spectrum Disorder.
AB  - Little research directly examines the needs of post-secondary students with ASD.
      The experiences and support needs of 23 students with ASD enrolled in two
      universities and four colleges, and 15 family members were explored in 15 semi
      structured focus groups. Thematic analysis identified five themes: core ASD
      features, co-morbid conditions, transition, disclosure, and services and support.
      Most students felt educationally but not socially supported; most families felt
      support was poor in both areas. Transition from secondary school was often
      unplanned, and disclosure of diagnosis usually occurred after enrolment, often
      following a significant problem. Many parents provided substantial student
      support. Thus disclosure of ASD diagnosis and meeting the individual needs of
      these students are important considerations as higher education enrolments
      increase. 

PMID- 26216382
TI  - FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat
      versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients
      with hematologic malignancies at intermediate to high TLS risk.
AB  - BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis
      syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We
      sought to determine whether febuxostat fixed dose achieves a better sUA control
      than allopurinol while preserving renal function in TLS prevention. PATIENTS AND
      METHODS: Patients with hematologic malignancies at intermediate to high TLS risk
      grade were randomized to receive febuxostat or allopurinol, starting 2 days
      before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas
      daily dose (low/standard/high containing allopurinol 200/300/600 mg,
      respectively, or fixed febuxostat 120 mg) depended on the investigator's choice.
      The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine
      change, were assessed from baseline to day 8 and analyzed through analysis of
      covariance with two-sided overall significance level of 5%. Secondary end points
      included treatment responder rate, laboratory and clinical TLS incidence and
      safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7%
      assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 +/- 225.71
      versus 708.0 +/- 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum
      creatinine change was -0.83 +/- 26.98% and -4.92 +/- 16.70% for febuxostat and
      allopurinol, respectively (P = 0.0903). No differences among secondary efficacy
      end points were detected. Drug-related adverse events occurred in 6.4% of
      patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS
      prevention, febuxostat achieved a significant superior sUA control with one fixed
      dose in comparison to allopurinol with comparable renal function preservation and
      safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.

PMID- 26216383
TI  - A phase I trial combining carboplatin/doxorubicin with tocilizumab, an anti-IL-6R
      monoclonal antibody, and interferon-alpha2b in patients with recurrent epithelial
      ovarian cancer.
AB  - BACKGROUND: The immune system is important in epithelial ovarian cancer (EOC).
      Interleukin-6 is associated with chemoresistance and an immune-suppressive tumor
      microenvironment. We investigated whether a combination of chemotherapeutics,
      blockade of interleukin 6 (IL-6) receptor (IL-6R; tocilizumab), and immune
      enhancer interferon-alpha (Peg-Intron) is feasible, safe, and able to enhance
      immunity in patients with recurrent EOC. PATIENTS AND METHODS: In this dose
      escalation study, patients received tocilizumab 1, 2, 4, or 8 mg/kg i.v., q4
      weeks during the first three cycles of carboplatin (AUC5) plus doxorubicin
      [pegylated liposomal doxorubicin (PLD) 30 mg/m(2) or doxorubicin 50 mg/m(2) i.v.,
      day 1, q4 weeks, for six cycles]. At the highest tocilizumab dose (8 mg/kg), Peg
      Intron (1 ug/kg s.c.) was added. Peripheral blood mononuclear cells were
      collected for immunomonitoring at baseline, after three and six cycles. Dose
      limiting toxicity (DLT), CA-125, and radiologic response were evaluated. RESULTS:
      In the 23 patients enrolled, no DLT was established. The most frequent grade 3/4
      adverse events (CTCAE v4.03) were neutropenia (23%), febrile neutropenia (19%),
      and ileus (19%). No treatment-related deaths occurred. Using CT evaluation, 11 of
      21 assessable patients responded, 6 had stable disease and 3 progressive disease.
      Patients receiving highest dose tocilizumab showed a functional blockade of IL-6R
      with increased levels of serum IL-6 (P = 0.02) and soluble IL-6R (P = 0.008).
      Consequently, immune cells displayed decreased levels of pSTAT3, myeloid cells
      produced more IL-12 and IL-1beta while T cells were more activated and secreted
      higher amounts of effector cytokines interferon-gamma and tumor necrosis factor
      alpha. An increase in sIL-6R was potentially associated with a survival benefit
      (P = 0.03). CONCLUSIONS: Functional IL-6R blocking is feasible and safe in EOC
      patients treated with carboplatin/(pegylated liposomal)doxorubicin, using 8 mg/kg
      tocilizumab. This combination is recommended for phase II evaluation based on
      immune parameters. CLINICAL TRIAL REGISTER: NCT01637532.

PMID- 26216384
TI  - Sunitinib administered on 2/1 schedule in patients with metastatic renal cell
      carcinoma: the RAINBOW analysis.
AB  - BACKGROUND: First-line sunitinib is recommended in metastatic renal cell
      carcinoma (mRCC), but it is frequently associated with relevant toxicities and
      subsequent dose reductions. Alternative schedules, such as 2-week-on treatment
      and 1-week-off (2/1 schedule), might improve tolerability. We evaluated the
      safety and outcomes of this schedule in a large multicenter analysis. PATIENTS
      AND METHODS: Retrospective, multicenter analysis of mRCC patients treated with
      first-line sunitinib on a 2/1 schedule. Data of 249 patients were reviewed: 208
      cases who started sunitinib on the 4/2 schedule (full dosage: 188/208, 90.4%) and
      thereafter switched to the 2/1 schedule for toxicity (group 4/2 -> 2/1) and 41
      patients who started first-line sunitinib with the 2/1 schedule because of
      suboptimal clinical conditions (group 2/1). A total of 211 consecutive patients
      treated with the 4/2 schedule in another institution served as external controls.
      Safety was the primary end point. Treatment duration (TD), progression-free
      survival (PFS) and overall survival (OS) were also analyzed. RESULTS: In group
      4/2 -> 2/1, the overall incidence of grade >= 3 toxicities was significantly
      reduced (from 45.7% to 8.2%, P < 0.001) after the switch to 2/1 schedule. This
      advantage was maintained also in the 106/188 cases (56.4%) who maintained the
      full dosage. Fatigue, hypertension, hand-foot syndrome and thrombocytopenia were
      less frequent. The incidence of grade >= 3 adverse events in the negatively
      selected group 2/1 (only 73.2% starting at full dose) was 26.8%, similar to what
      observed in the external control group (29.4%). Median TD was 28.2 months in the
      4/2 -> 2/1 group (total time spent with both schedules), 7.8 months in the 2/1
      group and 9.7 months in external controls. Median PFS was 30.2, 10.4 and 9.7
      months, respectively. Median OS was not reached, 23.2 and 27.8 months,
      respectively. CONCLUSIONS: mRCC patients who moved to a modified 2/1 schedule of
      sunitinib experience an improved safety profile compared with that observed
      during the initial 4/2 schedule.

PMID- 26216385
TI  - Carfilzomib and pomalidomide in patients with relapsed and/or refractory multiple
      myeloma with baseline risk factors.
AB  - While survival times have increased over the last decade, most patients with
      multiple myeloma (MM) eventually relapse and become refractory to therapy. The
      treatment of patients with relapsed and/or refractory MM is frequently further
      complicated by the presence of pre-existing comorbidities that arise from an
      advanced disease state and of toxicities stemming from prior antimyeloma
      treatment. Carfilzomib and pomalidomide have recently been approved for the
      treatment of patients with relapsed and refractory MM. While these agents
      represent important additions to the available treatment options, the
      identification of patients who may best benefit from the use of each of therapy
      is still being investigated. A number of patient-related and disease-related
      factors may impact treatment efficacy and/or tolerability, and the clinical
      presentation and medical history of each patient must be carefully considered to
      optimize treatment. Here, we review results from carfilzomib and pomalidomide
      clinical trials in patients with relapsed and/or refractory MM who also have
      baseline comorbidities or treatment-induced or disease-induced complications
      (including the presence of renal impairment, cardiac risk factors, peripheral
      neuropathy, or high-risk chromosomal abnormalities) to evaluate the safety and
      efficacy of the two agents in these difficult-to-treat patients and to provide
      treatment recommendations specific to each scenario. 

PMID- 26216386
TI  - Comparison of two different S-1 plus cisplatin dosing schedules as first-line
      chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter,
      randomized phase III trial (SOS).
AB  - BACKGROUND: Five-weekly S-1 plus cisplatin (SP5) is one of the standard first
      line regimens for advanced gastric cancer (GC), proven in a Japanese phase III
      study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin
      (SP3) was developed. PATIENTS AND METHODS: This multicenter, randomized, open
      label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and
      cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day
      on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free
      survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or
      gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either
      SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382). RESULTS:
      Between February 2009 and January 2012, 625 patients were randomized at 42 sites
      in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3
      48.6 months) in surviving patients, SP3 was not only noninferior but also
      superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR)
      = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority).
      There was no difference in overall survival (OS) between the groups (median 14.1
      versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with
      measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5
      arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or
      higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent
      in SP3. CONCLUSIONS: SP3 is superior to SP5 in terms of PFS. However, since the
      improvement in PFS was only slight and there was no difference in OS, both SP3
      and SP5 can be recommended as first-line treatments for patients with advanced
      GC.

PMID- 26216387
TI  - Management of advanced prostate cancer.

PMID- 26216388
TI  - Assessment of anticancer-treatment outcome in patients with metastatic castration
      resistant prostate cancer-going beyond PSA and imaging, a systematic literature
      review.
AB  - BACKGROUND: In the past years, there has been significant progress in anticancer
      drug development for patients with metastatic castration-resistant prostate
      cancer (CRPC). However, the current instruments to assess clinical treatment
      response have limitations and may not sufficiently reflect patient benefit. Our
      objective was to systematically identify tools to evaluate both patient benefit
      and clinical anticancer-treatment response as basis for an international
      consensus process and development of a specific pragmatic instrument for men with
      CRPC. METHODS: PubMed, Embase and CINAHL were searched to identify currently
      available tools to assess anticancer-treatment benefit, other than standard
      imaging procedures and prostate-specific antigen measurements, namely quality of
      life (QoL), detailed pain assessment, physical function and objective measures of
      other complex cancer-related syndromes in patients with CRPC. Additionally, all
      CRPC phase III trials published in the last 5 years were reviewed as well as
      studies using physical function tools in a general cancer population. The PRIMSA
      statement was followed for the systematic review process. RESULTS: The search
      generated 1096 hits, 185 full-text papers were screened and finally 73
      publications were included. Additional 89 publications were included by hand
      search. We identified a total of 98 tools used in CRPC trials and grouped these
      into three categories: 22 tools assessing QoL domains and subgroups, 47 tools for
      pain assessment and 29 tools for objective measures, mainly physical function and
      assessment of skeletal disease burden. CONCLUSION: A wide variety of assessment
      tools and also efforts to standardize and harmonize patient-reported outcomes and
      pain assessment were identified. However, the specific needs of the increasing
      CRPC population living longer with their incurable cancer are insufficiently
      captured and objective physical outcome measures are under-represented. In the
      age of new anticancer drug targets and principles, new methods to monitor patient
      relevant outcomes of antineoplastic therapy are of utmost importance.

PMID- 26216389
TI  - Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal
      Immunotherapy for Drug-Resistant Enterobacteriaceae.
AB  - All Enterobacteriaceae express a polysaccharide known as enterobacterial common
      antigen (ECA), which is an attractive target for the development of universally
      acting immunotherapies. The first chemical synthesis of ECA-derived
      oligosaccharides for the development of such therapies is described. A number of
      synthetic challenges had to be addressed, including the development of concise
      synthetic procedures for unusual monosaccharides, the selection of appropriate
      orthogonal protecting groups, the development of stereoselective glycosylation
      methods, appropriate timing for the introduction of the carboxylic acid groups on
      the ManpNAcA moieties, and the selection of appropriate conditions for the
      reduction of multiple azido moieties. The synthetic compounds were employed to
      uncover immunodominant moieties of ECA. Furthermore, a monoclonal antibody (mAb)
      was developed that binds to ECA and can selectively recognize a wide range of
      Enterobacteriaceae species. 

PMID- 26216390
TI  - Identifying Demand Responses to Illegal Drug Supply Interdictions.
AB  - Successful supply-side interdictions into illegal drug markets are predicated on
      the responsiveness of drug prices to enforcement and the price elasticity of
      demand for addictive drugs. We present causal estimates that targeted
      interventions aimed at methamphetamine input markets ('precursor control') can
      temporarily increase retail street prices, but methamphetamine consumption is
      weakly responsive to higher drug prices. After the supply interventions, purity
      adjusted prices increased then quickly returned to pre-treatment levels within 6
      12 months, demonstrating the short-term effects of precursor control. The price
      elasticity of methamphetamine demand is -0.13 to -0.21 for self-admitted drug
      treatment admissions and between -0.24 and -0.28 for hospital inpatient
      admissions. We find some evidence of a positive cross-price effect for cocaine,
      but we do not find robust evidence that increases in methamphetamine prices
      increased heroin, alcohol, or marijuana drug use. This study can inform policy
      discussions regarding other synthesized drugs, including illicit use of
      pharmaceuticals. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26216391
TI  - Stochastic simulation of radium-223 dichloride therapy at the sub-cellular level.
AB  - Radium-223 dichloride ((223)Ra) is an alpha particle emitter and a natural bone
      seeking radionuclide that is currently used for treating osteoblastic bone
      metastases associated with prostate cancer. The stochastic nature of alpha
      emission, hits and energy deposition poses some challenges for estimating
      radiation damage. In this paper we investigate the distribution of hits to cells
      by multiple alpha particles corresponding to a typical clinically delivered dose
      using a Monte Carlo model to simulate the stochastic effects. The number of hits
      and dose deposition were recorded in the cytoplasm and nucleus of each cell.
      Alpha particle tracks were also visualized. We found that the stochastic
      variation in dose deposited in cell nuclei ([Formula: see text]40%) can be
      attributed in part to the variation in LET with pathlength. We also found that
      [Formula: see text]18% of cell nuclei receive less than one sigma below the
      average dose per cell ([Formula: see text]15.4 Gy). One possible implication of
      this is that the efficacy of cell kill in alpha particle therapy need not rely
      solely on ionization clustering on DNA but possibly also on indirect DNA damage
      through the production of free radicals and ensuing intracellular signaling. 

PMID- 26216392
TI  - Anomalous Compression of D5(450)-C100 by Encapsulating La2C2 Cluster instead of
      La2.
AB  - We demonstrate that a finite-length (10,0) carbon nanotube (CNT) with two
      fullerene caps, namely D5(450)-C100, is an ideal prototype to study the
      mechanical responses of small CNTs upon endohedral metal doping. Encapsulation of
      a large La2C2 cluster inside D5(450)-C100 induces a 5% axial compression of the
      cage, as compared with the structure of La2@D5(450)-C100. Detailed
      crystallographic analyses reveal quantitively the flexibility of the
      [10]cyclacene-sidewall segment and the rigidity of the pentagon-dominating caps
      for the first time. The internal C2-unit acts as a molecular spring that attracts
      the surrounding cage carbon atoms through strong interactions with the two moving
      lanthanum ions. This is the first crystallographic observation of the axial
      compression of CNTs caused by the internal stress, which enhances our knowledge
      about the structural deformation of novel carbon allotropes at the atomic level. 

PMID- 26216394
TI  - Editorial Comment on "The Impact of Illicit Use of Amphetamine on Male Sexual
      Functions".

PMID- 26216393
TI  - Effects of cold acclimation on sugar metabolism and sugar-related gene expression
      in tea plant during the winter season.
AB  - Sugar plays an essential role in plant cold acclimation (CA), but the interaction
      between CA and sugar remains unclear in tea plants. In this study, during the
      whole winter season, we investigated the variations of sugar contents and the
      expression of a large number of sugar-related genes in tea leaves. Results
      indicated that cold tolerance of tea plant was improved with the development of
      CA during early winter season. At this stage, starch was dramatically degraded,
      whereas the content of total sugars and several specific sugars including
      sucrose, glucose and fructose were constantly elevated. Beyond the CA stage, the
      content of starch was maintained at a low level during winter hardiness (WH)
      period and then was elevated during de-acclimation (DC) period. Conversely, the
      content of sugar reached a peak at WH stage followed by a decrease during DC
      stage. Moreover, gene expression results showed that, during CA period, sugar
      metabolism-related genes exhibited different expression pattern, in which beta
      amylase gene (CsBAM), invertase gene (CsINV5) and raffinose synthase gene (CsRS2)
      engaged in starch, sucrose and raffinose metabolism respectively were solidly up
      regulated; the expressions of sugar transporters were stimulated in general
      except the down-regulations of CsSWEET2, 3, 16, CsERD6.7 and CsINT2;
      interestingly, the sugar-signaling related CsHXK3 and CsHXK2 had opposite
      expression patterns at the early stage of CA. These provided comprehensive
      insight into the effects of CA on carbohydrates indicating that sugar
      accumulation contributes to tea plant cold tolerance during winter season, and a
      simply model of sugar regulation in response to cold stimuli is proposed. 

PMID- 26216395
TI  - Magnetic resonance imaging assessment of the ventricular system in the brains of
      adult and juvenile beagle dogs treated with posaconazole IV Solution.
AB  - INTRODUCTION: Noxafil(r) (posaconazole; POS) is a potent, selective triazole
      antifungal approved for use in adults as an oral suspension, oral tablet and
      intravenous (IV) Solution. In support of pediatric administration of POS IV
      Solution to children<two years of age, a nonclinical study in juvenile pre
      weaning Beagle dogs was conducted, which showed enlarged lateral ventricles in
      the brain at the conclusion of a 6 week dosing period. METHODS: To evaluate the
      impact of this finding on older age dogs, which would support administration to
      children>two years of age, two studies were undertaken using magnetic resonance
      imaging (MRI) to monitor brain ventricle size longitudinally during three months
      administration of POS IV in adult and juvenile dogs. Necropsy was performed on
      all animals at the end of the studies. From the baseline MRI images, great
      variability in ventricle size was noted in both the adult and juvenile dogs;
      these images were used to distribute differently sized ventricles between
      treatment and vehicle groups as to not skew group means during the course of the
      study. RESULTS: POS IV Solution had no effect on ventricle volume at any
      timepoint during dosing in either the adult or the juvenile dogs. Further, no
      gross or histomorphologic differences between groups were observed in either
      study. Compared to juvenile dogs, MRI analysis showed that adult dogs had larger
      ventricles, lower variability in all ventricle volumes, and a greater rate of
      increase in total ventricle volume. DISCUSSION: Information on growth and
      development of brains is one of the few areas in which more detailed information
      is available about humans than about the standard laboratory animals used to
      model disease and predict toxicities. The use of MRI helped elucidate large
      natural variabilities in the dog brain, which could have altered the
      interpretation of this de-risking study, and provided a valuable noninvasive
      means to monitor the brain ventricles longitudinally.

PMID- 26216396
TI  - Multiple tissue response modifiers to promote angiogenesis and prevent the
      foreign body reaction around subcutaneous implants.
AB  - Dexamethasone-releasing PLGA poly(lactic-co-glycolic acid) microsphere/PVA
      (polyvinyl alcohol) hydrogel composite coatings have been shown to prevent the
      foreign body reaction (FBR) to subcutaneous implants in small and large animal
      models. Such coatings were developed to extend the lifetime of implantable
      biosensors. However, long-term exposure of tissue to low levels of dexamethasone
      results in a reduction in blood vessel density due to the anti-angiogenic effect
      of dexamethasone. This mild effect, while not threatening to the subject's
      health, may interfere with analyte detection and the sensor response time over
      the long-term. The present work is focused on the development of coatings that
      deliver combinations of three tissue response modifiers (TRMs): dexamethasone,
      VEGF (vascular endothelial growth factor) and PDGF (platelet derived growth
      factor). Dexamethasone, VEGF and PDGF prevent the FBR, increase angiogenesis and
      promote blood vessel maturation (which increases blood flow), respectively. To
      minimize any potential interference among these three TRMs (for example, PDGF
      increases fibrosis), the relative doses of dexamethasone, VEGF and PDGF were
      adjusted. It was determined that: a) all three TRMs are required for maximum
      promotion of angiogenesis, blood vessel maturation and prevention of the FBR; b)
      VEGF has to be administered at higher doses than PDGF; c) an increase in
      dexamethasone dosing must be accompanied by a proportional increase in growth
      factor dosing; and d) modification of the TRM ratio can achieve a constant
      capillary density throughout the implantation period which is important for
      applications such as biosensors to maintain sensitivity and a stable sensor
      baseline. Moreover, an osmosis-driven process for encapsulation of proteins in
      PLGA microspheres that showed low burst release was developed. 

PMID- 26216397
TI  - Mammalian cochlea as a physics guided evolution-optimized hearing sensor.
AB  - Nonlinear physics plays an essential role in hearing. We demonstrate on a
      mesoscopic description level that during the evolutionary perfection of the
      hearing sensor, nonlinear physics led to the unique design of the cochlea
      observed in mammals, and that this design requests as a consequence the
      perception of pitch. Our insight challenges the view that mostly genetics is
      responsible for the uniformity of the construction of the mammalian hearing
      sensor. Our analysis also suggests that scaleable and non-scaleable arrangements
      of nonlinear sound detectors may be at the origin of the differences between
      hearing sensors in amniotic lineages. 

PMID- 26216398
TI  - APP controls the formation of PI(3,5)P(2) vesicles through its binding of the
      PIKfyve complex.
AB  - Phosphoinositides are signalling lipids that are crucial for major signalling
      events as well as established regulators of membrane trafficking. Control of
      endosomal sorting and endosomal homeostasis requires phosphatidylinositol-3
      phosphate (PI(3)P) and phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), the
      latter a lipid of low abundance but significant physiological relevance.
      PI(3,5)P2 is formed by phosphorylation of PI(3)P by the PIKfyve complex which is
      crucial for maintaining endosomal homeostasis. Interestingly, loss of PIKfyve
      function results in dramatic neurodegeneration. Despite the significance of
      PIKfyve, its regulation is still poorly understood. Here we show that the Amyloid
      Precursor Protein (APP), a central molecule in Alzheimer's disease, associates
      with the PIKfyve complex (consisting of Vac14, PIKfyve and Fig4) and that the APP
      intracellular domain directly binds purified Vac14. We also show that the closely
      related APP paralogues, APLP1 and 2 associate with the PIKfyve complex. Whether
      APP family proteins can additionally form direct protein-protein interaction with
      PIKfyve or Fig4 remains to be explored. We show that APP binding to the PIKfyve
      complex drives formation of PI(3,5)P2 positive vesicles and that APP gene family
      members are required for supporting PIKfyve function. Interestingly, the PIKfyve
      complex is required for APP trafficking, suggesting a feedback loop in which APP,
      by binding to and stimulating PI(3,5)P2 vesicle formation may control its own
      trafficking. These data suggest that altered APP processing, as observed in
      Alzheimer's disease, may disrupt PI(3,5)P2 metabolism, endosomal sorting and
      homeostasis with important implications for our understanding of the mechanism of
      neurodegeneration in Alzheimer's disease. 

PMID- 26216399
TI  - Protective Role of Oleuropein against Acute Deltamethrin-Induced Neurotoxicity in
      Rat Brain.
AB  - BACKGROUND: Deltamethrin (DM) is a synthetic pyrethroid insecticide that can
      elicit neurotoxicity, leading to apoptosis. There is accumulating evidence that
      oleuropein (OE) has anti-apoptotic effect. The purpose of this study was to
      determine the anti-apoptotic effect of OE pretreatment in the neuronal cells of
      cerebral cortex. METHODS: Rats were randomly divided into four groups each
      containing five rats: DM-treated group (12.5 mg/kg, a single dose), OE-treated
      group (20 mg/kg per day), DM + OE-treated group, and vehicle group. Sections of
      the brain were obtained 24 hours after DM injection and studied for
      histopathological and immunohistochemistry assessment. RESULTS: The
      histopathological assessments showed lesser characteristics of neural
      degeneration in DM + OE group compared with DM group. Greater Bcl-2 and
      attenuated Bax expression could be detected in the DM + OE treated-mice compared
      with DM group. CONCLUSION: The results suggested that DM-induced neurotoxicity
      can be subsided by OE.

PMID- 26216400
TI  - Effects of Dietary Different Doses of Copper and High Fructose Feeding on Rat
      Fecal Metabolome.
AB  - The gut microbiota plays a critical role in the pathogenesis of nonalcoholic
      fatty liver disease (NAFLD). Increased fructose consumption and inadequate copper
      intake are two critical risk factors in the development of NAFLD. To gain insight
      into the role of gut microbiota, fecal metabolites, obtained from rats exposed to
      different dietary levels of copper with and without high fructose intake for 4
      weeks, were analyzed by comprehensive two-dimensional gas chromatography time-of
      flight mass spectrometry (GC * GC-TOF MS). In parallel, liver tissues were
      assessed by histology and triglyceride assay. Our data showed that high fructose
      feeding led to obvious hepatic steatosis in both marginal copper deficient rats
      and copper supplementation rats. Among the 38 metabolites detected with
      significant abundance alteration between groups, short chain fatty acids were
      markedly decreased with excessive fructose intake irrespective of copper levels.
      C15:0 and C17:0 long chain fatty acids, produced only by bacteria, were increased
      by either high copper level or high fructose intake. In addition, increased fecal
      urea and malic acid paralleled the increased hepatic fat accumulation.
      Collectively, GC * GC-TOF MS analysis of rat fecal samples revealed distinct
      fecal metabolome profiles associated with the dietary high fructose and copper
      level, with some metabolites possibly serving as potential noninvasive biomarkers
      of fructose induced-NAFLD. 

PMID- 26216401
TI  - The authors respond.

PMID- 26216402
TI  - Effectiveness, usability, and cost-benefit of a virtual reality-based
      telerehabilitation program for balance recovery after stroke: a randomized
      controlled trial.

PMID- 26216403
TI  - It is time for bowel-omics.

PMID- 26216404
TI  - The authors respond.

PMID- 26216405
TI  - Cycling with functional electrical stimulation after spinal cord injury: what's
      in it for me?

PMID- 26216406
TI  - IL-9 signaling affects central nervous system resident cells during inflammatory
      stimuli.
AB  - Interleukin (IL) 9, a dominant cytokine in Th9 cells, has been proven to play a
      pathogenic role in experimental autoimmune encephalomyelitis (EAE), an animal
      model of multiple sclerosis (MS), by augmenting T cell activation and
      differentiation; however, whether IL-9 signaling affects central nervous system
      (CNS)-resident cells during CNS autoimmunity remains unknown. In the present
      study, we found that the IL-9 receptor (IL-9R) was highly expressed in
      astrocytes, oligodendrocyte progenitor cells (OPCs), oligodendrocytes and
      microglia cells, and that its expression was significantly upregulated in brain
      and spinal cord during EAE. In addition, IL-9 increased chemokine expression,
      including CXCL9, CCL20 and MMP3, in primary astrocytes. Although IL-9 had no
      effect on the proliferation of microglia cells, it decreased OPC proliferation
      and differentiation when in combination with other pro-inflammatory cytokines,
      but not with IFN-gamma. IL-9 plus IFN-gamma promoted OPC proliferation and
      differentiation. These findings indicate that CNS-restricted IL-9 signaling may
      be involved in the pathogenesis of MS/EAE, thus providing a potential therapeutic
      target for future MS/EAE treatment through disruption of CNS cell-specific IL-9
      signaling. 

PMID- 26216407
TI  - The anti-fibrotic effects of microRNA-153 by targeting TGFBR-2 in pulmonary
      fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial fibrotic lung
      disease with an undefined etiology and no effective treatments. By binding to
      cell surface receptors, transforming growth factor-beta (TGF-beta) plays a
      pivotal role in lung fibrosis. Therefore, the screening of microRNAs (miRNAs),
      especially those interrupting the effects of TGF-beta, may provide information
      not only on the pathomechanism, but also on the treatment of this disease. In the
      present study, we found that miR-153 expression was dysregulated in the lungs of
      mice with experimental pulmonary fibrosis and TGF-beta1 decreased miR-153
      expression in pulmonary fibroblasts. Moreover, increased miR-153 levels
      attenuated, whereas the knock down of miR-153 promoted the pro-fibrogenic
      activity of TGF-beta1, and miR-153 reduced the contractile and migratory
      activities of fibroblasts. In addition, TGFBR2, a transmembrane serine/threonine
      kinase receptor for TGF-beta, was identified as a direct target of miR-153.
      Furthermore, by post-transcriptional regulation of the expression of TGFBR2,
      phosphorylation of SMAD2/3 was also influenced by miR-153. These data suggest
      that miR-153 disturbs TGF-beta1 signal transduction and its effects on fibroblast
      activation, acting as an anti-fibrotic element in the development of pulmonary
      fibrosis. 

PMID- 26216408
TI  - Erratum: Oligometastases in prostate cancer: restaging stage IV cancers and new
      radiotherapy options.

PMID- 26216409
TI  - The receptor for advanced glycation end products and risk of peripheral arterial
      disease, amputation or death in type 2 diabetes: a population-based cohort study.
AB  - BACKGROUND: Patients with type 2 diabetes have a high risk for early and
      extensive development of peripheral arterial disease (PAD) and this excess risk
      is not explained by increased burden of traditional atherosclerotic risk factors.
      Activation of the receptor for advanced glycation end products (RAGE) could be
      one additional mechanism for accelerated PAD and increased risk for amputation
      and death. We investigated the association between RAGE plasma components and the
      risk for PAD, amputation and death in patients with type 2 diabetes. We also
      estimated the rate of amputation-free survival and survival without PAD. METHODS:
      We investigated if plasma levels of carboxymethyl-lysine, S100A12 and
      endosecretory RAGE (esRAGE) were associated with two endpoints: survival without
      development of PAD and survival without amputation in a 12 years prospective
      population-based cohort of 146 patients with type 2 diabetes, free from PAD at
      inclusion. Influence of baseline plasma levels of RAGE ligands (individually and
      combined by a RAGE-score) were evaluated for both endpoints in the Cox-regression
      analysis. RESULTS: 106 patients survived without amputation and 93 survived
      without signs of PAD during follow up. Higher levels of S100A12 and RAGE-score
      were associated with increased risk for amputation or death, hazard ratios (HR)
      1.29; 95% confidence interval (CI) [1.04, 1.59] and 1.79; 95% CI [1.07, 2.99] and
      with increased risk for PAD or death, HR 1.22; 95% CI [1.00, 1.49] and 1.56;
      [1.00, 2.44] after adjustment for age and sex. The effect was decreased after
      adjustment for Framingham cardiovascular disease score: risk for amputation or
      death, HR 1.17; 95% CI [0.94, 1.46] and 1.54; [0.95, 2.49], and risk for PAD or
      death, HR 1.12; 95% CI [0.91, 1.38] and 1.38; [0.91, 2.11] for S100A12 and RAGE
      score respectively. The incidence for amputation or death was 2.8 per 100 person
      years; 95% CI [2.0, 3.7] and the incidence rate for PAD or death was 3.6 per 100
      person-years; 95% CI [2.7, 4.8]. CONCLUSION: Higher plasma levels of S100A12 and
      the combined effect (RAGE-score) of esRAGE, carboxymethyl-lysine and S100A12 seem
      to be associated with shorter PAD- and amputation-free survival in patients with
      type 2 diabetes. This may indicate a role for S100A12 in PAD by activation of the
      RAGE system.

PMID- 26216410
TI  - Absolute position versus relative position in embryo transfer: a randomized
      controlled trial.
AB  - BACKGROUND: Meta-analysis revealed that embryo placement 20 mm from the fundal
      endometrial surface resulted in higher pregnancy rate, ongoing pregnancy rate,
      and live birth rate compared with placement 10 mm from the fundal endometrial
      surface. Pregnancy and implantation rates according to relative position were
      higher when the catheter tip was positioned close to the middle of the
      endometrial cavity. The aim of the current study is to evaluate differences in
      implantation and pregnancy rates if the site of embryo transfer is 2 cm distance
      from the fundal endometrium (DFE) compared to the midpoint of the endometrial
      cavity length (ECL). METHODS: Patients were randomized to one of two groups: in
      group A (n = 98, 98 IVF-ET cycles), the embryo transfer catheter tip was
      positioned 2 cm DFE, while that in group B (n = 97, 97 IVF-ET cycles) was
      positioned at the midpoint of the ECL. We compared pregnancy outcomes of
      implantation rate, chemical pregnancy rate, clinical pregnancy rate, ongoing
      pregnancy rate, ectopic pregnancy rate, and miscarriage rate in the two groups.
      RESULTS: Analysis of implantation rate (19.5 +/- 27.7 vs. 21.7 +/- 32.6; p =
      0.6), chemical pregnancy rate (51 % vs. 50.5 %; p = 0.94), clinical pregnancy
      rate (35.7 % vs. 38.1 %; p = 0.73), ongoing pregnancy rate (31.6 % vs. 30.9 %; p
      = 0.92), ectopic pregnancy rate (8.6 % vs. 2.7 %; p = 0.35), and miscarriage rate
      (11.4 % vs. 16.2 %; 0.74) revealed comparable results for both groups.
      CONCLUSIONS: Implantation and pregnancy rates were not influenced by the site of
      the ET catheter tip being 2 cm DFE compared to at the midpoint of the ECL. TRIAL
      REGISTRATION:  ISRCTN: ISRCTN15972342.

PMID- 26216411
TI  - Microemulsion based gel for topical dermal delivery of pseudolaric acid B: In
      vitro and in vivo evaluation.
AB  - Pseudolaric acid B (PAB) possesses comparable fungicidal activity against Candida
      albicans to amphotericin B and antifungal activity against azole-resistant
      Candida species. However, its poor water solubility makes the formulation a
      considerable challenge for dermal permeation of PAB. The aim of this project was
      to improve the solubility and eventually the dermal permeability and
      bioavailability by developing a microemulsion based gel for PAB (PAB ME-gel). PAB
      ME-gel was formulated using isopropyl myristate as oil phase, cremphor EL as
      surfactant, transcutol P as cosurfactant, and carbopol as gel matrix, and
      characterized by droplet size, morphology, pH, and rheology. The 3 month storage
      test showed that PAB ME-gel possessed good physicochemical stability. In vitro
      permeation of PAB through rat skin from ME-gel was investigated in comparison
      with PAB microemulsion (PAB ME) and PAB hydrogel (PAB gel), and results showed
      that ME significantly enhanced PAB retention in the skin and permeation through
      the skin whether it was incorporated into the gel or not. In vivo
      dermatopharmacokinetics study using microdialysis further confirmed that ME-gel
      significantly increased PAB dermal bioavailability compared with the gel (41.95
      +/- 8.89 MUg/ml vs. 13.90 +/- 2.22 MUg/ml). In vitro sensitivity against C.
      albicans test indicated that the antifungal activity of PAB ME-gel increased with
      the increase of PAB loading, and 8 mg/g of PAB ME-gel exhibited a higher
      antifungal activity than that of 20mg/g miconazole nitrate cream. In vivo
      antifungal activity evaluation in C. albicans infected guinea pigs showed that 8
      mg/g of PAB ME-gel exhibited a higher efficacy than that of 20mg/g miconazole
      nitrate cream after 7 day treatment. Overall, the results indicated that the ME
      enhanced in vitro permeability, in vivo dermal bioavailability, and antifungal
      activity of PAB. Therefore, ME-gel may be a promising approach for topical dermal
      delivery of PAB to treat skin fungal infection.

PMID- 26216412
TI  - The prediction of the palatability of orally disintegrating tablets by an
      electronic gustatory system.
AB  - In this study, the human gustatory palatability sensation of taste-masked
      famotidine and amlodipine orally disintegrating tablets (ODTs) was quantitatively
      predicted by an electronic gustatory system (alpha-Astree e-Tongue). Furthermore,
      its use in formulation design was evaluated. The famotidine- and amlodipine
      containing ODTs, which were bitter- and highly bitter-tasting, respectively, were
      prepared using a physical (granules spray-coated with ethyl cellulose) or
      organoleptic (the addition of a sweetener and a flavor) masking method and
      combinations thereof. The taste-masking effects of different masking methods on
      the ODTs were investigated in a human gustatory sensation test. In the test,
      volunteers scored the overall palatability using a 100mm visual analog scale
      (VAS). The electronic gustatory system was evaluated using the Euclidean distance
      (the distance between each drug-containing ODT and its corresponding placebo) and
      partial least squares (PLS) regression analysis of the sensor response values. A
      good linear relationship was observed between each ODT's Euclidean distance
      analysis, PLS regression analysis, and clinical VAS scores. Cross-validation
      verification of each analysis confirmed the model's predictive power. This study
      suggests that the alpha-Astree can quantitatively evaluate physical and
      organoleptic taste masking and that the palatability of unknown formulations can
      be predicted by Euclidean distance and PLS regression data analysis. 

PMID- 26216413
TI  - Nanoparticle encapsulation and controlled release of a hydrophobic kinase
      inhibitor: Three stage mathematical modeling and parametric analysis.
AB  - A mathematical model of drug release that incorporates the simultaneous
      contributions of initial burst, nanoparticle degradation-relaxation and diffusion
      was developed and used to effectively describe the release of a kinase inhibitor
      and anticancer drug, PHT-427. The encapsulation of this drug into PLGA
      nanoparticles was performed by following the single emulsion-solvent evaporation
      technique and the release was determined in phosphate buffer pH 7.4 at 37 
      degrees C. The size of nanoparticles was obtained in a range of 162-254 nm. The
      experimental release profiles showed three well defined phases: an initial fast
      drug release, followed by a nanoparticle degradation-relaxation slower release
      and then a diffusion release phase. The effects of the controlled release most
      relevant parameters such as drug diffusivity, initial burst constant,
      nanoparticle degradation-relaxation constant, and the time to achieve a maximum
      rate of drug release were evaluated by a parametrical analysis. The theoretical
      release studies were corroborated experimentally by evaluating the cytotoxicity
      effectiveness of the inhibitor AKT/PDK1 loaded nanoparticles over BxPC-3
      pancreatic cancer cells in vitro. These studies show that the encapsulated
      inhibitor AKT/PDK1 in the nanoparticles is more accessible and thus more
      effective when compared with the drug alone, indicating their potential use in
      chemotherapeutic applications.

PMID- 26216414
TI  - Dry state microcrystals stabilized by an HPMC film to improve the bioavailability
      of andrographolide.
AB  - OBJECTIVE: The main purpose of this study was to improve the in-vitro dissolution
      and the in-vivo bioavailability of a poorly water-soluble drug, andrographolide
      (ADG). METHODS: A wet-milled suspension was prepared using a Lab basket mill in
      the presence of a hydrophilic carrier solution and then it was layered on to MCC
      beads with a fluidized bed coater to obtain solidified pellets. Optical
      microscopy, particle size distribution investigation, differential scanning
      calorimetry (DSC) and powder X-ray diffraction (PXRD) were used to characterize
      the wet-milled suspension. In addition, the ADG pellets were subjected to
      investigations involving scanning electron microscopy (SEM), as well as
      dissolution, accelerated stability and bioavailability measurements. RESULTS: The
      particle size was significantly reduced (from 31.6 MUm to 2.17 MUm), however, the
      ADG in suspension retained its crystallinity as shown by the results of the DSC
      and PXRD investigations. The dissolution of the new pellets and commercial
      dripping pills was 95.6% and 48%, respectively, in pure water over 60 min. After
      a 6 month accelerated test (40 degrees C and RH 75%), although the initial
      dissolution rate declined slightly, the overall dissolution of the new pellets
      within 60 min was almost as high as the freshly prepared pellets. In the in-vivo
      evaluation, the Cmax (87.54 +/- 54.82 MUg/L) and AUC(0-t) of the new pellets
      (495.86 +/- 281.05 MUg/Lh) were clearly higher than those of the dripping pills
      (30.88 +/- 12.02 MUg/L, 301.07 +/- 133.85 MUg/Lh), while the Tmax of the test
      preparation was shorter than that of the reference (1.38 h vs 3.29 h).
      CONCLUSION: These results showed that the new core-shell structured pellets
      consisting of ADG microcrystalline particles and stabilized by HPMC alone,
      markedly improved the dissolution and bioavailability of andrographolide.

PMID- 26216415
TI  - Development of orodispersible polymer films containing poorly water soluble
      active pharmaceutical ingredients with focus on different drug loadings and
      storage stability.
AB  - The aim of this work was the development of orodispersible films containing
      different film forming polymers with focus on different drug loadings of two
      poorly water soluble APIs. Furthermore, physical stability of films was examined
      at two different storage conditions. Loperamide hydrochloride (LPH) and ibuprofen
      (IBU) were used as model drugs. Hydroxypropyl methylcellulose (HPMC) and three
      different types of hydroxypropyl cellulose (HPC) were used as film forming
      polymers. Suspensions were characterized with respect to their viscosity and
      particle sedimentation and films regarding their content uniformity, thickness,
      mass and stability. Principal component analysis (PCA) was used to evaluate the
      correlation between the wet film thickness, dry film thickness, mass of the
      films, API fraction in the suspension and the viscosity of the suspensions. The
      viscosity of the suspensions was dependent on the drug load and the polymer
      fraction but less so on the type of the utilized polymer. A correlation between
      the wet film thickness, the solid fraction and the mass of the films was
      established with an increase in mass by increasing the wet film thickness or the
      solid fraction. Films containing 50 mg IBU/6 cm(2) film led to acceptable films.
      Storage experiments did not lead to an AV below 15 in all cases after storage for
      three and six months, attributed to the storage conditions and the quality of the
      films. Nevertheless, the development and production of flexible and homogeneous
      films of LPH and IBU was successfully achieved.

PMID- 26216416
TI  - Complement Factor H Antibodies from Lung Cancer Patients Induce Complement
      Dependent Lysis of Tumor Cells, Suggesting a Novel Immunotherapeutic Strategy.
AB  - Characterization of the humoral immune response in selected patients with cancer
      who uniformly do well may lead to the development of novel therapeutic
      strategies. We have previously shown an association between patients with early
      stage nonmetastatic lung cancer and autoantibodies to complement factor H (CFH).
      CFH protects normal and tumor cells from destruction by the alternative
      complement pathway by inactivating C3b, a protein that is essential for formation
      of a lytic complex on the cell surface. Here, we show that CFH autoantibodies in
      lung cancer patients recognize a conformationally distinct form of CFH in vitro,
      are IgG3 subclass, and epitope map to a crucial functional domain of CFH known to
      interact with C3b. Purified CFH autoantibodies inhibited binding of CFH to A549
      lung tumor cells, increased C3b deposition, and caused complement-dependent tumor
      cell lysis. This work demonstrates that CFH autoantibodies isolated from patients
      with lung cancer can kill tumor cells in vitro, suggesting that they may perform
      this function in vivo as well. Development of specific antibodies to the
      conformationally distinct epitope of CFH may lead to a useful biologic therapy
      for lung cancer.

PMID- 26216417
TI  - Intrathecal Administration of Tumor-Infiltrating Lymphocytes Is Well Tolerated in
      a Patient with Leptomeningeal Disease from Metastatic Melanoma: A Case Report.
AB  - Patients with leptomeningeal disease (LMD) from melanoma have very poor outcomes
      and few treatment options. We present a case of intrathecal (i.t.) administration
      of autologous tumor-infiltrating lymphocytes (TIL) in a patient with LMD from
      metastatic melanoma. The patient developed LMD after previous treatments with
      surgery, high-dose bolus interleukin-2 (HD IL2), and systemic TIL infusion and
      experienced radiographic progression after intrathecal IL2 (i.t. IL2) therapy.
      The patient received weekly treatment with increasing numbers of i.t. TIL
      followed by twice-weekly i.t. IL2. The patient received three i.t. TIL infusions
      and did not experience any toxicities beyond those expected with i.t. IL2
      therapy. Analysis of cerebrospinal fluid demonstrated increased inflammatory
      cytokines following the i.t. TREATMENTS: Subsequent imaging demonstrated disease
      stabilization, and neurological deficits also remained stable. The patient
      expired 5 months after the initiation of i.t. TIL therapy with disease
      progression in the brain, liver, lung, and peritoneal and retroperitoneal lymph
      nodes, but without LMD progression. These results demonstrate the safety of i.t.
      administration of TIL in melanoma patients with LMD and support the feasibility
      of conducting a prospective clinical trial to determine this therapy's clinical
      benefit among these patients.

PMID- 26216418
TI  - Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia
      haemolytica Leukotoxin in Bighorn Sheep.
AB  - Mannheimia haemolytica causes pneumonia in domestic and wild ruminants.
      Leukotoxin (Lkt) is the most important virulence factor of the bacterium. It is
      encoded within the four-gene lktCABD operon: lktA encodes the structural
      protoxin, and lktC encodes a trans-acylase that adds fatty acid chains to
      internal lysine residues in the protoxin, which is then secreted from the cell by
      a type 1 secretion system apparatus encoded by lktB and lktD. It has been
      reported that LktC-mediated acylation is necessary for the biological effects of
      the toxin. However, an LktC mutant that we developed previously was only
      partially attenuated in its virulence for cattle. The objective of this study was
      to elucidate the role of LktC-mediated acylation in Lkt-induced cytotoxicity. We
      performed this study in bighorn sheep (Ovis canadensis) (BHS), since they are
      highly susceptible to M. haemolytica infection. The LktC mutant caused fatal
      pneumonia in 40% of inoculated BHS. On necropsy, a large number of necrotic
      polymorphonuclear leukocytes (PMNs) were observed in the lungs. Lkt from the
      mutant was cytotoxic to BHS PMNs in an in vitro cytotoxicity assay. Flow
      cytometric analysis of mutant Lkt-treated PMNs revealed the induction of
      necrosis. Scanning electron microscopic analysis revealed the presence of pores
      and blebs on mutant-Lkt-treated PMNs. Mass spectrometric analysis confirmed that
      the mutant secreted an unacylated Lkt. Taken together, these results suggest that
      acylation is not necessary for the cytotoxic activity of M. haemolytica Lkt but
      that it enhances the potency of the toxin. 

PMID- 26216419
TI  - Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus
      Pneumonia.
AB  - Th17 immunity in the gastrointestinal tract is regulated by the intestinal
      microbiota composition, particularly the presence of segmented filamentous
      bacteria (sfb), but the role of the intestinal microbiota in pulmonary host
      defense is not well explored. We tested whether altering the gut microbiota by
      acquiring sfb influences the susceptibility to staphylococcal pneumonia via
      induction of type 17 immunity. Groups of C57BL/6 mice which differed in their
      intestinal colonization with sfb were challenged with methicillin-resistant
      Staphylococcus aureus in an acute lung infection model. Bacterial burdens,
      bronchoalveolar lavage fluid (BALF) cell counts, cell types, and cytokine levels
      were compared between mice from different vendors, mice from both vendors after
      cohousing, mice given sfb orally prior to infection, and mice with and without
      exogenous interleukin-22 (IL-22) or anti-IL-22 antibodies. Mice lacking sfb
      developed more severe S. aureus pneumonia than mice colonized with sfb, as
      indicated by higher bacterial burdens in the lungs, lung inflammation, and
      mortality. This difference was reduced when sfb-negative mice acquired sfb in
      their gut microbiota through cohousing with sfb-positive mice or when given sfb
      orally. Levels of type 17 immune effectors in the lung were higher after
      infection in sfb-positive mice and increased in sfb-negative mice after
      acquisition of sfb, as demonstrated by higher levels of IL-22 and larger numbers
      of IL-22(+) TCRbeta(+) cells and neutrophils in BALF. Exogenous IL-22 protected
      mice from S. aureus pneumonia. The murine gut microbiota, particularly the
      presence of sfb, promotes pulmonary type 17 immunity and resistance to S. aureus
      pneumonia, and IL-22 protects against severe pulmonary staphylococcal infection. 

PMID- 26216420
TI  - Legionella pneumophila Effector LpdA Is a Palmitoylated Phospholipase D Virulence
      Factor.
AB  - Legionella pneumophila is a bacterial pathogen that thrives in alveolar
      macrophages, causing a severe pneumonia. The virulence of L. pneumophila depends
      on its Dot/Icm type IV secretion system (T4SS), which delivers more than 300
      effector proteins into the host, where they rewire cellular signaling to
      establish a replication-permissive niche, the Legionella-containing vacuole
      (LCV). Biogenesis of the LCV requires substantial redirection of vesicle
      trafficking and remodeling of intracellular membranes. In order to achieve this,
      several T4SS effectors target regulators of membrane trafficking, while others
      resemble lipases. Here, we characterized LpdA, a phospholipase D effector, which
      was previously proposed to modulate the lipid composition of the LCV. We found
      that ectopically expressed LpdA was targeted to the plasma membrane and Rab4- and
      Rab14-containing vesicles. Subcellular targeting of LpdA required a C-terminal
      motif, which is posttranslationally modified by S-palmitoylation. Substrate
      specificity assays showed that LpdA hydrolyzed phosphatidylinositol, -inositol-3-
      and -4-phosphate, and phosphatidylglycerol to phosphatidic acid (PA) in vitro. In
      HeLa cells, LpdA generated PA at vesicles and the plasma membrane. Imaging of
      different phosphatidylinositol phosphate (PIP) and organelle markers revealed
      that while LpdA did not impact on membrane association of various PIP probes, it
      triggered fragmentation of the Golgi apparatus. Importantly, although LpdA is
      translocated inefficiently into cultured cells, an L. pneumophila DeltalpdA
      mutant displayed reduced replication in murine lungs, suggesting that it is a
      virulence factor contributing to L. pneumophila infection in vivo. 

PMID- 26216421
TI  - Influenza and Bacterial Superinfection: Illuminating the Immunologic Mechanisms
      of Disease.
AB  - Seasonal influenza virus infection presents a major strain on the health care
      system. Influenza virus infection has pandemic potential, which was repeatedly
      observed during the last century. Severe disease may occur in the young, in the
      elderly, in those with preexisting lung disease, and in previously healthy
      individuals. A common cause of severe influenza pathogenesis is superinfection
      with bacterial pathogens, namely, Staphylococcus aureus and Streptococcus
      pneumoniae. A great deal of recent research has focused on the immune pathways
      involved in influenza-induced susceptibility to secondary bacterial pneumonia.
      Both innate and adaptive antibacterial host defenses are impaired in the context
      of preceding influenza virus infection. The goal of this minireview is to
      highlight these findings and synthesize these data into a shared central theme of
      pathogenesis. 

PMID- 26216422
TI  - Multiple Plasmodium falciparum Erythrocyte Membrane Protein 1 Variants per Genome
      Can Bind IgM via Its Fc Fragment FcMU.
AB  - The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) adhesive
      proteins expressed on the surfaces of infected erythrocytes (IEs) are of key
      importance in the pathogenesis of P. falciparum malaria. Several structurally and
      functionally defined PfEMP1 types have been associated with severe clinical
      manifestations, such as cerebral malaria in children and placental malaria in
      pregnant women. PfEMP1 that can bind the Fc part of IgM (FcMU) characterizes one
      such type, although the functional significance of this IgM binding to PfEMP1
      remains unclear. In this study, we report the identification and functional
      analysis of five IgM-binding PfEMP1 proteins encoded by P. falciparum NF54. In
      addition to the VAR2CSA-type PFL0030c protein, already known to bind FcMU and to
      mediate chondroitin sulfate A (CSA)-specific adhesion of IEs in the placenta, we
      found four PfEMP1 proteins not previously known to bind IgM this way. Although
      they all contained Duffy binding-like epsilon (DBLepsilon) domains similar to
      those in VAR2CSA-type PfEMP1, they did not mediate IE adhesion to CSA, and IgM
      binding did not shield IEs from phagocytosis of IgG-opsonized IEs. In this way,
      these new IgM-binding PfEMP1 proteins resemble the rosette-mediating and IgM
      binding PfEMP1 HB3VAR06, but none of them mediated formation of rosettes. We
      could map the capacity for Fc-specific IgM binding to DBLepsilon domains near the
      C terminus for three of the four PfEMP1 proteins tested. Our study provides new
      evidence regarding Fc-dependent binding of IgM to PfEMP1, which appears to be a
      common and multifunctional phenotype. 

PMID- 26216423
TI  - Adherent-Invasive Escherichia coli Production of Cellulose Influences Iron
      Induced Bacterial Aggregation, Phagocytosis, and Induction of Colitis.
AB  - Adherent-invasive Escherichia coli (AIEC), a functionally distinct subset of
      resident intestinal E. coli associated with Crohn's disease, is characterized by
      enhanced epithelial adhesion and invasion, survival within macrophages, and
      biofilm formation. Environmental factors, such as iron, modulate E. coli
      production of extracellular structures, which in turn influence the formation of
      multicellular communities, such as biofilms, and bacterial interactions with host
      cells. However, the physiological and functional responses of AIEC to variable
      iron availability have not been thoroughly investigated. We therefore
      characterized the impact of iron on the physiology of AIEC strain NC101 and
      subsequent interactions with macrophages. Iron promoted the cellulose-dependent
      aggregation of NC101. Bacterial cells recovered from the aggregates were more
      susceptible to phagocytosis than planktonic cells, which corresponded with the
      decreased macrophage production of the proinflammatory cytokine interleukin-12
      (IL-12) p40. Prevention of aggregate formation through the disruption of
      cellulose production reduced the phagocytosis of iron-exposed NC101. In contrast,
      under iron-limiting conditions, where NC101 aggregation is not induced, the
      disruption of cellulose production enhanced NC101 phagocytosis and decreased
      macrophage secretion of IL-12 p40. Finally, abrogation of cellulose production
      reduced NC101 induction of colitis when NC101 was monoassociated in inflammation
      prone Il10(-/-) mice. Taken together, our results introduce cellulose as a novel
      physiological factor that impacts host-microbe-environment interactions and
      alters the proinflammatory potential of AIEC. 

PMID- 26216424
TI  - Activation of Hepatic STAT3 Maintains Pulmonary Defense during Endotoxemia.
AB  - Pneumonia and infection-induced sepsis are worldwide public health concerns. Both
      pathologies elicit systemic inflammation and induce a robust acute-phase response
      (APR). Although APR activation is well regarded as a hallmark of infection, the
      direct contributions of liver activation to pulmonary defense during sepsis
      remain unclear. By targeting STAT3-dependent acute-phase changes in the liver, we
      evaluated the role of liver STAT3 activity in promoting host defense in the
      context of sepsis and pneumonia. We employed a two-hit endotoxemia/pneumonia
      model, whereby administration of 18 h of intraperitoneal lipopolysaccharide (LPS;
      5 mg/kg of body weight) was followed by intratracheal Escherichia coli (10(6)
      CFU) in wild-type mice or those lacking hepatocyte STAT3 (hepSTAT3(-/-)).
      Pneumonia alone (without endotoxemia) was effectively controlled in the absence
      of liver STAT3. Following endotoxemia and pneumonia, however, hepSTAT3(-/-) mice,
      with significantly reduced levels of circulating and airspace acute-phase
      proteins, exhibited significantly elevated lung and blood bacterial burdens and
      mortality. These data suggested that STAT3-dependent liver responses are
      necessary to promote host defense. While neither recruited airspace neutrophils
      nor lung injury was altered in endotoxemic hepSTAT3(-/-) mice, alveolar
      macrophage reactive oxygen species generation was significantly decreased.
      Additionally, bronchoalveolar lavage fluid from this group of hepSTAT3(-/-) mice
      allowed greater bacterial growth ex vivo. These results suggest that hepatic
      STAT3 activation promotes both cellular and humoral lung defenses. Taken
      together, induction of liver STAT3-dependent gene expression programs is
      essential to countering the deleterious consequences of sepsis on pneumonia
      susceptibility. 

PMID- 26216425
TI  - Identification of Conserved and Species-Specific Functions of the Listeria
      monocytogenes PrsA2 Secretion Chaperone.
AB  - The Gram-positive bacterium Listeria monocytogenes is a facultative intracellular
      pathogen that relies on the regulated secretion and activity of a variety of
      proteins that sustain life within diverse environments. PrsA2 has recently been
      identified as a secreted peptidyl-prolyl cis/trans isomerase and chaperone that
      is dispensable for bacterial growth in broth culture but essential for L.
      monocytogenes virulence. Following host infection, PrsA2 contributes to the
      proper folding and activity of secreted proteins that are required for bacterial
      replication within the host cytosol and for bacterial spread to adjacent cells.
      PrsA2 is one member of a family of Gram-positive secretion chaperones that appear
      to play important roles in bacterial physiology; however, it is not known how
      these proteins recognize their substrate proteins or the degree to which their
      function is conserved across diverse Gram-positive species. We therefore examined
      PrsA proteins encoded by a variety of Gram-positive bacteria for functional
      complementation of L. monocytogenes mutants lacking prsA2. PrsA homologues
      encoded by Bacillus subtilis, Streptococcus pyogenes, Streptococcus pneumoniae,
      Streptococcus mutans, Staphylococcus aureus, and Lactococcus lactis were examined
      for functional complementation of a variety of L. monocytogenes PrsA2-associated
      phenotypes central to L. monocytogenes pathogenesis and bacterial cell
      physiology. Our results indicate that while selected aspects of PrsA2 function
      are broadly conserved among diverse Gram-positive bacteria, PrsA2 exhibits unique
      specificity for L. monocytogenes target proteins required for pathogenesis. The
      L. monocytogenes PrsA2 chaperone thus appears evolutionarily optimized for
      virulence factor secretion within the host cell cytosol while still maintaining
      aspects of activity relevant to more general features of Gram-positive protein
      translocation. 

PMID- 26216426
TI  - Comparable Genital Tract Infection, Pathology, and Immunity in Rhesus Macaques
      Inoculated with Wild-Type or Plasmid-Deficient Chlamydia trachomatis Serovar D.
AB  - Rhesus macaques were studied to directly address the potential for plasmid
      deficient Chlamydia trachomatis to serve as a live attenuated vaccine in the
      genital tract. Five repeated cervical inoculations of rhesus macaques with wild
      type serovar D strain D/UW-3/Cx or a plasmid-deficient derivative of this strain,
      CTD153, resulted in infections with similar kinetics and induced comparable
      levels of protective immunity. After all animals received five challenges with
      D/UW-3/Cx, levels of inflammation observed grossly and histologically were
      similar between the groups. Animals in both groups developed evidence of oviduct
      dilatation; however, reduced oviduct dilatation was observed for "controllers,"
      i.e., animals without detectable chlamydial DNA in the fimbriae at weeks 5 and
      12. Grouping animals into "ascenders" and "controllers" revealed that elevated
      early T cell responses were associated with protection, whereas higher antibody
      responses were associated with ascension. Protected animals shared common major
      histocompatibility complex (MHC) alleles. Overall, genetic differences of
      individual animals, rather than the presence or absence of the chlamydial plasmid
      in the primary infecting strain, appeared to play a role in determining the
      outcome of infection. 

PMID- 26216427
TI  - The Aggregatibacter actinomycetemcomitans Cytolethal Distending Toxin Active
      Subunit CdtB Contains a Cholesterol Recognition Sequence Required for Toxin
      Binding and Subunit Internalization.
AB  - Induction of cell cycle arrest in lymphocytes following exposure to the
      Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) is
      dependent upon the integrity of lipid membrane microdomains. Moreover, we have
      previously demonstrated that the association of Cdt with target cells involves
      the CdtC subunit which binds to cholesterol via a cholesterol recognition amino
      acid consensus sequence (CRAC site). In this study, we demonstrate that the
      active Cdt subunit, CdtB, also is capable of binding to large unilamellar
      vesicles (LUVs) containing cholesterol. Furthermore, CdtB binding to cholesterol
      involves a similar CRAC site as that demonstrated for CdtC. Mutation of the CRAC
      site reduces binding to model membranes as well as toxin binding and CdtB
      internalization in both Jurkat cells and human macrophages. A concomitant
      reduction in Cdt-induced toxicity was also noted, indicated by reduced cell cycle
      arrest and apoptosis in Jurkat cells and a reduction in the proinflammatory
      response in macrophages (interleukin 1beta [IL-1beta] and tumor necrosis factor
      alpha [TNF-alpha] release). Collectively, these observations indicate that
      membrane cholesterol serves as an essential ligand for both CdtC and CdtB and,
      further, that this binding is necessary for both internalization of CdtB and
      subsequent molecular events leading to intoxication of cells. 

PMID- 26216428
TI  - Propionibacterium acnes Recovered from Atherosclerotic Human Carotid Arteries
      Undergoes Biofilm Dispersion and Releases Lipolytic and Proteolytic Enzymes in
      Response to Norepinephrine Challenge In Vitro.
AB  - In the present study, human atherosclerotic carotid arteries were examined
      following endarterectomy for the presence of the Gram-positive bacterium
      Propionibacterium acnes and its potential association with biofilm structures
      within the arterial wall. The P. acnes 16S rRNA gene was detectable in 4 of 15
      carotid artery samples, and viable P. acnes was one among 10 different bacterial
      species recoverable in culture. Fluorescence in situ hybridization analysis of 5
      additional atherosclerotic carotid arteries demonstrated biofilm bacteria within
      all samples, with P. acnes detectable in 4 samples. We also demonstrated that
      laboratory-grown cultures of P. acnes biofilms were susceptible to induction of a
      biofilm dispersion response when challenged with physiologically relevant levels
      of norepinephrine in the presence of iron-bound transferrin or with free iron.
      The production and release of lipolytic and proteolytic extracellular enzymes by
      P. acnes were shown to increase in iron-induced dispersed biofilms, and these
      dispersion-induced P. acnes VP1 biofilms showed increased expression of mRNAs for
      the triacylglycerol lipases PPA2105 and PPA1796 and the hyaluronate lyase PPA380
      compared to that in untreated biofilms. These results demonstrate that P. acnes
      can infect the carotid arteries of humans with atherosclerosis as a component of
      multispecies biofilms and that dispersion is inducible for this organism, at
      least in vitro, with physiologically relevant levels of norepinephrine resulting
      in the production and release of degradative enzymes. 

PMID- 26216429
TI  - Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative
      Vacuole Similar to That of Legionella pneumophila despite Translocation of
      Distinct Effector Repertoires.
AB  - Legionella organisms are environmental bacteria and accidental human pathogens
      that can cause severe pneumonia, termed Legionnaires' disease. These bacteria
      replicate within a pathogen-derived vacuole termed the Legionella-containing
      vacuole (LCV). Our understanding of the development and dynamics of this vacuole
      is based on extensive analysis of Legionella pneumophila. Here, we have
      characterized the Legionella longbeachae replicative vacuole (longbeachae-LCV)
      and demonstrated that, despite important genomic differences, key features of the
      replicative LCV are comparable to those of the LCV of L. pneumophila (pneumophila
      LCV). We constructed a Dot/Icm-deficient strain by deleting dotB and demonstrated
      the inability of this mutant to replicate inside THP-1 cells. L. longbeachae does
      not enter THP-1 cells as efficiently as L. pneumophila, and this is reflected in
      the observation that translocation of BlaM-RalFLLO (where RalFLLO is the L.
      longbeachae homologue of RalF) into THP-1 cells by the L. longbeachae Dot/Icm
      system is less efficient than that by L. pneumophila. This difference is negated
      in A549 cells where L. longbeachae and L. pneumophila infect with similar entry
      dynamics. A beta-lactamase assay was employed to demonstrate the translocation of
      a novel family of proteins, the Rab-like effector (Rle) proteins.
      Immunofluorescence analysis confirmed that these proteins enter the host cell
      during infection and display distinct subcellular localizations, with RleA and
      RleC present on the longbeachae-LCV. We observed that the host Rab GTPase, Rab1,
      and the v-SNARE Sec22b are also recruited to the longbeachae-LCV during the early
      stages of infection, coinciding with the LCV avoiding endocytic maturation. These
      studies further our understanding of the L. longbeachae replicative vacuole,
      highlighting phenotypic similarities to the vacuole of L. pneumophila as well as
      unique aspects of LCV biology. 

PMID- 26216430
TI  - Characterization of the renal renin-angiotensin system in transgenic mice that
      express rat tonin.
AB  - INTRODUCTION: Tonin is an enzyme that is able to generate angiotensin II (Ang II)
      from angiotensin I (Ang I) or directly from angiotensinogen. Our goal was to
      characterize the renal renin-angiotensin system in transgenic mice that express
      rat tonin (TGM'(rTon)). MATERIALS AND METHODS: Mice were euthanized and the
      kidneys removed for analysis. Tonin activity was evaluated by radioimmunoassay
      and angiotensin I-converting enzyme (ACE) activity by HPLC. Tonin, ACE and
      angiotensin II-converting enzyme (ACE2) expression was analyzed by Western
      blotting. RESULTS: Tonin activity was significantly increased in TGM'(rTon)
      compared to their respective wild-type (WT) littermates (1.7 +/- 0.21 vs 0.11 +/-
      0.02 nmol of Ang II/min/mg of protein). Tonin activity had a strong positive
      correlation with tonin expression in both TGM'(rTon) and their respective wild
      type littermates. The ACE activity and expression levels of 65-kDa N-domain
      angiotensin I-converting enzyme isoform were significantly increased in the
      TGM'(rTon) when compared with WT. ACE2 expression levels were statistically
      significantly higher in the TGM'(rTon) when compared with WT. Angiotensin 1-7
      (Ang(1-7)) and Ang I levels were significantly lower in the TGM'(rTon).
      CONCLUSIONS: We suggest that the environment of tonin abundance may increase N
      domain ACE activity liberated by a secretase able to cleave somatic ACE.

PMID- 26216431
TI  - Age effects on EEG correlates of the Wisconsin Card Sorting Test.
AB  - Body and brain undergo several changes with aging. One of the domains in which
      these changes are more remarkable relates with cognitive performance. In the
      present work, electroencephalogram (EEG) markers (power spectral density and
      spectral coherence) of age-related cognitive decline were sought whilst the
      subjects performed the Wisconsin Card Sorting Test (WCST). Considering the
      expected age-related cognitive deficits, WCST was applied to young, mid-age and
      elderly participants, and the theta and alpha frequency bands were analyzed. From
      the results herein presented, higher theta and alpha power were found to be
      associated with a good performance in the WCST of younger subjects. Additionally,
      higher theta and alpha coherence were also associated with good performance and
      were shown to decline with age and a decrease in alpha peak frequency seems to be
      associated with aging. Additionally, inter-hemispheric long-range coherences and
      parietal theta power were identified as age-independent EEG correlates of
      cognitive performance. In summary, these data reveals age-dependent as well as
      age-independent EEG correlates of cognitive performance that contribute to the
      understanding of brain aging and related cognitive deficits. 

PMID- 26216432
TI  - Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2
      synthesis.
AB  - Leukotriene D4 (LTD4) is a pro-inflammatory mediator formed from arachidonic acid
      through the action of 5-lipoxygenase (5-LOX). Its biological effects are mediated
      by at least two G-coupled plasmatic cysteinyl LT receptors (CysLT1-2R). It has
      been reported an upregulation of the 5-LOX pathway in tumor tissue unlike in
      normal colon mucosa. Colon tumors generally have an increased expression of
      CysLT1R and colon cancer patients with high expression levels of CysLT1R have
      poor prognosis. We previously observed that the cyclooxygenase pathway is
      involved in the control of intestinal epithelial cancer cell growth through PGE2
      production. The aim of this study was therefore to assess the effect of LTD4
      binding with CysLT1R on Caco-2 cell growth. We note a number of key findings from
      this research. We observed that at a concentration similar to that found under
      inflammatory conditions, LTD4 was able to induce Caco-2 cell proliferation and
      DNA synthesis. Moreover, with the use of a specific receptor antagonist this
      study has demonstrated that the effect of LTD4 is a result of its interaction
      with CystLT1R. We also note the possible participation of the PLC-IP3-Ca(2+)/DAG
      PKC signaling pathways in cytosolic PLA2 and [(3)H]AA release induced by LTD4
      CystLT1R interaction. Finally, we found that the resulting activation of the AA
      cascade and the production of PGE2 eicosanoid could be related to the activation
      of cell signaling pathways such as ERK and CREB. These findings will help
      facilitate our understanding of how inflammatory mediators can affect the
      survival and dissemination of intestinal carcinoma cells. 

PMID- 26216433
TI  - Pancreatic functions in high salt fed female rats.
AB  - Salt consumption has been increased worldwide and the association of high salt
      diets with enhanced inflammation and target organ damage was reported. Little
      data were available about the effect of high salt diet on exocrine function of
      pancreas, while the relation between high salt intake and insulin sensitivity was
      controversial. This study was designed to investigate the effect of high salt
      diet on exocrine and endocrine pancreatic functions, and to elucidate the
      possible underlying mechanism(s). Twenty adult female Wistar rats were randomly
      divided into two groups; control group; fed standard rodent diet containing 0.3%
      NaCl, and high salt fed group; fed 8% NaCl for 8 weeks. On the day of sacrifice,
      rats were anesthized by i.p. pentobarbitone (40 MUg/kg B.W.). Nasoanal length was
      measured and fasting blood glucose was determined from rat tail. Blood samples
      were obtained from abdominal aorta for determination of plasma sodium, potassium,
      amylase, lipase, aldosterone, insulin, transforming growth factor-beta (TGF
      beta1), and interleukin 6 (IL6). Pancreata of both groups were histologically
      studied. Compared to control group, 8-week high salt fed group showed:
      significant elevation in body weight, body mass index, Lee index, plasma sodium,
      TGF-beta1 and IL6, however, plasma aldosterone, amylase, lipase, and insulin
      levels were significantly decreased. A nonsignificant increase in plasma
      potassium and nonsignificant changes in fasting blood glucose and HOMA-IR were
      detected between groups. Pancreatic fibrosis was observed in test group. High
      salt diet for 8 weeks caused pancreatic fibrosis evidenced by decline of both
      exocrine and endocrine functions of pancreas in Wistar rats. 

PMID- 26216435
TI  - Editorial: Breast Cancer Clinical Trials--The Era of the Surrogates.

PMID- 26216434
TI  - Caesarean section rates in subgroups of women and perinatal outcomes.
AB  - OBJECTIVES: To identify factors that are associated with a relatively low
      caesarean section (CS) rate by examining the CS rate in various subgroups in the
      Netherlands. DESIGN: Cross-sectional analysis. SETTINGS: the Netherlands.
      POPULATION: A total of 685 452 births in the Netherlands Perinatal Registry from
      2007 to 2010. METHODS: A modified classification system for CS was used to
      categorise all women into ten groups. Labour management, mode of delivery,
      maternal and neonatal morbidity and mortality were assessed according to these
      ten groups. MAIN OUTCOME MEASURES: Caesarean section, labour induction,
      instrumental delivery, postpartum haemorrhage, perineal laceration, duration of
      second stage of labour, Apgar score, fetal and neonatal mortality. RESULTS: Total
      CS rate was 15.6%. Term, nulliparous and parous women with a singleton pregnancy
      of a fetus in cephalic position and spontaneous onset of labour had CS rates of
      9.6 and 1.9% and instrumental birth rates of 19.4 and 2.4%, respectively; 17.3%
      of births were induced. Among women with a previous CS and term, singleton
      pregnancies with a fetus in cephalic presentation, 71% had trial of labour, of
      which 75% had a successful vaginal birth. Of women with multiple gestation, 43%
      had CS. Women with CS due to 'failure to progress' in the second stage of labour
      had a median duration of second-stage pushing of almost 2 hours in nulliparas and
      >90 minutes in parous women. CONCLUSIONS: Several obstetric practice patterns may
      have contributed to the relatively low overall CS rate in the Netherlands: a
      relatively low CS rate in term, singleton pregnancies of a fetus in cephalic
      position and spontaneous onset of labour, relatively low rate of labour
      induction, a high rate of a trial of labour after a previous CS, the use of
      vacuum and forceps, and a high proportion of women being taken care of by
      midwives. TWEETABLE ABSTRACT: The Netherlands has several practice patterns that
      may have contributed to its relatively low CS rate.

PMID- 26216436
TI  - Role of Anti-HER-2 Therapies in the Neo-Adjuvant Setting: Is Complete
      Pathological Response a Solid Surrogate?
AB  - Breast cancer continues to be a major health problem. Both patients and
      clinicians demand faster access to drugs that could result in better outcomes. In
      part motivated by this necessity, there has been a change in the dominant
      paradigm regarding how drugs become approved. Complete pathological response
      (pCR), understood as the absence of remanent and viable tumor after a neoadjuvant
      treatment, is now considered by a large proportion of the medical community as a
      valid surrogate. The presumption is that patients achieving pCR are less likely
      to develop tumor recurrence. Consequently, if a drug can improve the number of
      patients achieving pCR it could then obtain approval by the regulatory agencies.
      Pertuzumab, an anti-HER- 2 monoclonal antibody, was granted accelerated approval
      based on this principle. The unprecedented approval of this drug is now an
      example that can help us to understand the advantages but also the potential
      risks associated with this new approach. In this review, we will discuss the
      results of the two clinical trials leading to the FDA-approval of pertuzumab in
      the neo-adjuvant setting. We will also analyze the outcomes from long term follow
      up of two important neoadjuvant clinical trials, the NeoALTTO and the NOAH
      studies. These last ones had provided further insights regarding the magnitude,
      the quality as well as some limitations of the relationship between pCR and
      harder endpoints such as event-free or overall survival. It seems evident that
      the acknowledgement of pCR as a potential surrogate endpoint represents an
      important step in the right direction. However, it still remains controversial
      whether this is applicable to all subtypes of breast cancers. Additional
      investigations may be necessary to safely generalize this concept. 

PMID- 26216437
TI  - Anti-Hormonal Therapies for Premenopausal Patients--What did we Learn from the
      TEXT/SOFT Trials?
AB  - Between 20-25% of all breast cancers are diagnosed in patients younger than 50
      years of age, most of whom are still premenopausal. Currently, tamoxifen is
      considered the standard of care for adjuvant treatment in these cases. However,
      in postmenopausal women, aromatase inhibitors (AIs) are a better choice. Given
      the superiority of AIs over tamoxifen in postmenopausal women, multiple
      investigators explored the potential role of AIs in premenopausal patients
      receiving ovarian suppression. Until very recently, available data derived from
      the ABCSG-12 clinical trial argued against the combination of AIs and ovarian
      suppression. This idea, however, may have changed with the release of the
      combined analysis of two clinical trials: SOFT and TEXT which evaluated the use
      of ovarian suppression in combination therapy. Clinicians will soon reconsider
      the possibility of using this strategy for premenopausal patients. Given the
      availability of this new data this review will analyze the consequences derived
      from this study, contextualize this new information within the vast available
      literature of anti-hormonal therapy, and discuss potential arguments in favor of
      and against the use of this approach. 

PMID- 26216438
TI  - The Efficacy and Safety of Eberconazole Nitrate 1% and Mometasone Furoate 0.1%
      w/w Cream in Subjects with Inflamed Cutaneous Mycoses.
AB  - BACKGROUND: Topical antifungal agents along with the steroids may provide not
      only rapid symptomatic relief but also clearance of disease causing fungi in
      inflamed cutaneous mycoses (ICM). AIM: To assess the efficacy and safety of fixed
      dose combination (FDC) of Eberconazole nitrate 1% and Mometasone furoate 0.1% w/w
      cream, in subjects with ICM. METHODS: This was a multi-centric, non-comparative
      study conducted in 155 eligible adult Indian subjects with ICM. They were treated
      with study medication for 21 days (D21) and followed up on day 35 (D35). Efficacy
      (by Investigator's Static Global Assessment-ISGA, symptom severity scores) and
      safety were assessed to evaluate the therapeutic response. RESULTS: Of 155
      subjects, 129 completed the study. Lesions healed completely in 77.52% and
      improved markedly in 22.48% patients by D21. There was a statistically
      significant reduction (p<0.001) in total symptom score (TSS) and mean severity
      scores of erythema, scaling and pruritus on days 7 and 21 compared to baseline.
      There was no treatment failure. Only 11 patients remained culture positive on D21
      compared to 68 at baseline. Physicians evaluated the drug as 'Good' in 72% and
      'Excellent' in 28% of subjects; adverse events were reported in 27.74% subjects
      and none was severe. There was a decrease in serum cortisol level in 4.52%
      (7/155) subjects and was considered clinically significant in three subjects. On
      D35, 18.55% and 24.20% subjects had greater ISGA score and TSS respectively,
      compared to D21. CONCLUSION: Tested FDC demonstrated efficacy and was well
      tolerated by study population. It offers an effective and safe therapeutic option
      for the management of ICM.

PMID- 26216439
TI  - Erratum to "Hyperactive PiggyBac Transposons for Sustained and Robust Liver
      targeted Gene Therapy".

PMID- 26216440
TI  - Haloarchaea Endowed with Phosphorus Solubilization Attribute Implicated in
      Phosphorus Cycle.
AB  - Archaea are unique microorganisms that are present in ecological niches of high
      temperature, pH and salinity. A total of 157 archaea were obtained from thirteen
      sediment, water and rhizospheric soil samples collected from Rann of Kutch,
      Gujarat, India. With an aim to screen phosphate solubilizing archaea, a new
      medium was designed as Haloarchaea P Solubilization (HPS) medium. The medium
      supported the growth and P solubilization activity of archaea. Employing the HPS
      medium, twenty isolates showed the P-solubilization. Phosphate solubilizing
      archaea were identified as seventeen distinct species of eleven genera namely
      Haloarcula, Halobacterium, Halococcus, Haloferax, Halolamina, Halosarcina,
      Halostagnicola, Haloterrigena, Natrialba, Natrinema and Natronoarchaeum.
      Natrinema sp. strain IARI-WRAB2 was identified as the most efficient P
      solubilizer (134.61 mg/L) followed by Halococcus hamelinensis strain IARI-SNS2
      (112.56 mg/L). HPLC analysis detected seven different kinds of organic acids,
      namely: gluconic acid, citric acid, formic acid, fumaric acid succinic acid,
      propionic acid and tartaric acid from the cultures of these isolates. These
      phosphate solubilizing halophilic archaea may play a role in P nutrition to
      vegetation growing in these hypersaline soils. This is the first report for these
      haloarchaea to solubilize considerable amount of P by production of organic acids
      and lowering of pH.

PMID- 26216441
TI  - The Effect of Surface Treatments on the Bond Strength Between CAD/CAM Blocks and
      Composite Resin.
AB  - PURPOSE: The aim of this study was to evaluate the microtensile bond strength of
      three computer-aided design/computer-aided manufacturing (CAD/CAM) blocks
      repaired with composite resin using three surface treatment techniques. METHODS
      AND MATERIALS: Three different CAD/CAM blocks were used in this study: (1)
      Lithium disilicate, (2) feldspar ceramic, and (3) resin nano ceramic. All groups
      were further divided into four subgroups according to surface treatment: control,
      roughened with bur (B); roughened with bur and 5% Hydrofluoric acid (HF);
      roughened with bur and sandblasting (HF); and roughened with bur and CoJet (C).
      After surface treatments on each group, a silane and bonding agent were applied,
      and ceramics were repaired with a nano-hybrid composite. Then, the repaired
      ceramics were cut with a low-speed diamond saw for microtensile bond testing.
      Microtensile bond tests for 40 specimens per subgroup were carried out with a
      universal testing machine. The data were analyzed with ANOVA, Tukey's, and LSD at
      the 95% significance level. RESULTS: Mean bond strengths (MPa) of subgroups B,
      HF, S, and C were: 0, 29.8, 0, 23.3 for lithium disilicate ceramic; 26.4, 22.3,
      22.4, 22 for feldspar ceramic; 54.8, 25.3, 42.1, 25.7 for resin nano ceramic. For
      subgroups B and S of lithium disilicate ceramics, bonding failed during specimen
      preparation. No significant differences were observed among all CoJet groups. In
      subgroups B and S, resin nano ceramics showed the highest bond strength. In
      feldspar groups, subgroup B showed higher bond strength than the other subgroups.
      CONCLUSION: This study demonstrates that lithium disilicate porcelain blocks
      required etching for repairing with composite material. Surface treatments did
      not increase the bond strength in feldspar ceramic groups and reduced the bond
      strength in resin nano ceramic groups.

PMID- 26216442
TI  - Erratum: Results of a Survey of Insurance Holders on Cure Regimes Performed in
      Foreign European Countries.

PMID- 26216443
TI  - [Development, Application and Evaluation of a Concept for Safe Patient
      Identification in Hospital - How can Knowledge Transfer Succeed?]

PMID- 26216444
TI  - N(1)-methylspermidine, a stable spermidine analog, prolongs anagen and regulates
      epithelial stem cell functions in human hair follicles.
AB  - Spermidine (Spd), the prototypic polyamine, has been shown to be essential for
      hair follicle (HF) growth. However, Spd can be readily converted into other
      polyamines, and is physiologically unstable. Therefore, to assess its individual
      functions on HFs, we used the metabolically stable Spd analog N(1)
      methylspermidine (N(1)-MeSpd). N(1)-MeSpd was confirmed to be a metabolically
      stable compound, with a half life of 90 h. 0.5 uM N(1)-MeSpd strongly prolonged
      anagen and decreased cell apoptosis in HFs in culture after 6 days, accompanied
      by specific stimulation of the expression of the epithelial stem cell-associated
      keratin, K15. N(1)-MeSpd also reduced lactate dehydrogenase activity in the
      culture supernatant, a parameter of cell death and cell lysis. N(1)-MeSpd
      diminished intracellular reactive oxygen species production in cultured
      keratinocytes, and reduced tumor necrosis factor-alpha, interleukin (IL)-1beta
      and IL-6 gene and protein expression after lipopolysaccharide stimulation. This
      suggests that some effects of N(1)-MeSpd may be mediated by anti-oxidative and
      anti-inflammatory effects. These additional properties of N(1)-MeSpd could be
      clinically important for the treatment of inflammatory alopecias and inflammatory
      scalp diseases.

PMID- 26216445
TI  - Hard-templating of Prussian blue analogues in mesoporous silica and organosilica.
AB  - Prussian blue analogues (PBAs) have been constructed in chiral nematic mesoporous
      organosilica and silica templates. By functionalizing the surface of the
      mesoporous hosts with bipyridinium ligands, it was possible to construct PBAs in
      their interiors through hard templating. The optical properties of the composites
      were studied and the relationship between the circular dichroism (CD) signals and
      the UV-Vis absorption spectra was found through mathematical modeling. Efforts to
      remove the hard templates to give free-standing PBA films with high surface area
      and pore volume were met with limited success, but it was possible in the case of
      zinc/iron PBAs to obtain a highly porous PBA sponge that retained the overall
      morphology of the template. This work demonstrates the potential for hard
      templating of coordination polymers in mesoporous materials. 

PMID- 26216446
TI  - Restoration of CBX7 expression increases the susceptibility of human lung
      carcinoma cells to irinotecan treatment.
AB  - Lung cancer is one of the most common causes of cancer-related death worldwide in
      men and women, and, despite the recent remarkable scientific advances, drug
      treatment is still unsatisfactory. Polycomb protein chromobox homolog 7 (CBX7) is
      involved in several biological processes, including development and cancer
      progression, indeed the lack of CBX7 protein correlates with a highly malignant
      phenotype and a poor prognosis. However, its role in lung cancer still remains
      unknown. Since CBX7 is drastically downregulated in human lung carcinomas, we
      investigated whether restoration of CBX7 expression could affect growth property
      of lung cancer cells and modulate their sensitivity to treatment with irinotecan
      and etoposide, two chemoterapy drugs most commonly used in lung cancer therapy.
      Here, we demonstrate that restoration of CBX7 in two human lung carcinoma cell
      lines (A549 and H1299), in which this protein is not detectable, leads to a
      decreased proliferation (at least in part through a downregulation of
      phosphorylated ERK and phosphorylated p38) and an increased apoptotic cell death
      after drug exposure (at least in part through the downregulation of Bcl-2,
      phosphorylated Akt, and phosphorylated JNK). Taken together, these results
      suggest that the retention of CBX7 expression may play a role in the modulation
      of chemosensitivity of lung cancer patients to the treatment with irinotecan and
      etoposide. 

PMID- 26216447
TI  - Comparative functional selectivity of imidafenacin and propiverine,
      antimuscarinic agents, for the urinary bladder over colon in conscious rats.
AB  - Antimuscarinics are the first-line choice of treatment for overactive bladder
      (OAB). Imidafenacin distributes in the bladder more selectively than in the
      submaxillary gland and colon, and hence, this drug is considered more useful for
      OAB than other antimuscarinics. However, the examination of imidafenacin
      selectivity to bladder over colon using in vivo models is limited. Thus, the
      author examined whether imidafenacin could induce more selective blockade of the
      bladder over colon in conscious rats using two pharmacological indices (colonic
      transit and neostigmine-induced fecal pellet output) and compared its bladder
      selectivity with propiverine. In the bladder study, the inhibitory doses of
      antimuscarinics were calculated using the area under the curve of the distension
      induced rhythmic contraction in conscious rats. The relative bladder selectivity
      of imidafenacin to propiverine was 50-fold and 61-fold, respectively, in a dye
      marker colonic transit model and in a neostigmine-induced fecal pellet output
      model. This comparative study shows that the functional bladder selectivity of
      imidafenacin is higher than that of propiverine tested under the present
      conditions in conscious rats. 

PMID- 26216449
TI  - Gender differences in symptom predictors associated with acute coronary syndrome:
      A prospective observational study.
AB  - Signs and symptoms (typical and atypical symptoms) of acute coronary syndromes
      (ACS) differ between men and women. Identification of gender differences has
      implications for both health care providers and the general public. The aim of
      this study was to determine the symptom predictors of the acute coronary
      syndromes in men and women. In this prospective study, nurse data collectors
      directly observed 256 men and 182 women (N = 438) with symptoms suggestive of ACS
      in the Emergency Departments of eight hospitals in Tehran. ACS was eventually
      diagnosed in 183 (57.2%) men and 137 (42.8%) women on the basis of standard
      electrocardiogram and cardiac enzyme (CPK-MB) level. In men, chest symptoms (OR =
      3.22, CI = 0.137-0.756, P = 0.009), dyspnea (OR = 2.65, CI = 1.78-4.123 P =
      0.001) and diaphoresis (OR = 2.175, CI = 1.020-4.639, P = 0.044) were
      significantly associated with the diagnosis of ACS 3.78, 2.72 and 1.87 times more
      than in women having these symptoms, respectively. These results indicated that
      chest symptoms, diaphoresis and dyspnea were the more pronounced typical symptoms
      of ACS in men compared to women. Additionally, the numbers of typical symptoms
      can be considered as more predictive of ACS in men (OR = 1.673, CI = 1.211-2.224,
      P < 0.001) than women (OR = 1.271, CI = 1.157-2.331, P = 0.212). Therefore,
      clinicians need to take men showing typical symptoms into consideration
      carefully. 

PMID- 26216448
TI  - Partial inhibition of the ubiquitin-proteasome system ameliorates cardiac
      dysfunction following ischemia-reperfusion in the presence of high glucose.
AB  - BACKGROUND: Acute hyperglycemia co-presenting with myocardial infarction (in
      diabetic and non-diabetic individuals) is often associated with a poor prognosis.
      Although acute hyperglycemia induces oxidative stress that can lead to
      dysregulation of the ubiquitin-proteasome system (UPS), it is unclear whether
      increased/decreased UPS is detrimental with ischemia-reperfusion under such
      conditions. As our earlier data implicated the UPS in cardiac damage, we
      hypothesized that its inhibition results in cardioprotection with ischemia
      reperfusion performed under conditions that simulate acute hyperglycemia.
      METHODS: Ex vivo rat heart perfusions were performed with Krebs-Henseleit buffer
      containing 33 mM glucose vs. controls (11 mM glucose) for 60 min stabilization,
      followed by 20 min global ischemia and 60 min reperfusion +/- 5 uM lactacystin
      and 10 uM MG-132, respectively. The UPS inhibitors were added during the first 20
      min of the reperfusion phase and various cardiac functional parameters evaluated.
      In parallel experiments, infarct sizes were assessed following 20 min regional
      ischemia and 120 min reperfusion +/- each of the respective UPS inhibitors (added
      during reperfusion). Heart tissues were collected and analyzed for markers of
      oxidative stress, UPS activation, inflammation and autophagy. RESULTS: The
      proteasome inhibitor doses and treatment duration here employed resulted in
      partial UPS inhibition during the reperfusion phase. Both lactacystin and MG-132
      administration resulted in cardioprotection in our experimental system, with MG
      132 showing a greater effect. The proteasome inhibitors also enhanced cardiac
      superoxide dismutase protein levels (SOD1, SOD2), attenuated pro-inflammatory
      effects and caused an upregulation of autophagic markers. CONCLUSIONS: This study
      established that partial proteasome inhibition elicits cardioprotection in hearts
      exposed to ischemia-reperfusion with acute simulated hyperglycemia. These data
      reveal that protease inhibition triggered three major protective effects, i.e.
      (a) enhancing myocardial anti-oxidant defenses, (b) attenuating inflammation, and
      (c) increasing the autophagic response. Thus the UPS emerges as a unique
      therapeutic target for the treatment of ischemic heart disease under such
      conditions.

PMID- 26216450
TI  - Vaccination after treatment of patients with human papillomavirus-positive oral
      and oropharyngeal disease - what are we waiting for?

PMID- 26216451
TI  - Distinct 18S rRNA precursors are targets of the exosome complex, the
      exoribonuclease RRP6L2 and the terminal nucleotidyltransferase TRL in Arabidopsis
      thaliana.
AB  - The biosynthesis of ribosomal RNA and its incorporation into functional ribosomes
      is an essential and intricate process that includes production of mature
      ribosomal RNA from large precursors. Here, we analyse the contribution of the
      plant exosome and its co-factors to processing and degradation of 18S pre-RNAs in
      Arabidopsis thaliana. Our data show that, unlike in yeast and humans, an RRP6
      homologue, the nucleolar exoribonuclease RRP6L2, and the exosome complex,
      together with RRP44, function in two distinct steps of pre-18S rRNA processing or
      degradation in Arabidopsis. In addition, we identify TRL (TRF4/5-like) as the
      terminal nucleotidyltransferase that is mainly responsible for oligoadenylation
      of rRNA precursors in Arabidopsis. We show that TRL is required for efficient
      elimination of the excised 5' external transcribed spacer and of 18S maturation
      intermediates that escaped 5' processing. Our data also suggest involvement of
      additional nucleotidyltransferases, including terminal uridylyltransferase(s), in
      modifying rRNA processing intermediates in plants. 

PMID- 26216452
TI  - Increased platelet reactivity in Klinefelter men: something new to consider.
AB  - Patients with Klinefelter syndrome (KS) exhibit an increased cardiovascular risk,
      but underlying mechanisms are largely unknown. The present cross-sectional study
      has been conducted to evaluate platelet reactivity and the expression of platelet
      activation markers (8-iso-prostaglandin F2alpha[8-iso-PGF2alpha] and 11-dehydro
      thromboxane-B2[11-dehydro-TXB2]) in KS patients and healthy controls. Twenty
      three consecutive KS patients under testosterone replacement therapy have been
      included as case group and 46 age-matched healthy males recruited among hospital
      staff served as controls. Light transmission aggregometry was performed in both
      cases and controls and maximal platelet aggregation (max-A%) was defined as
      maximal light transmittance reached within 5 min after the addition of 0.2 or 0.4
      mm arachidonic acid (AA). A >= 50% irreversible light transmittance (LT-50%)
      following platelet stimulation defined an adequate platelet aggregation and AC
      50% was defined as the minimal agonist concentration needed to achieve LT-50%.
      The AC-50% was 0.26 mm AA for KS and 0.36 mm for controls (p < 0.001). Whereas AA
      (0.2 mm) induced LT-50% in 69.6% of KS and in 15.2% of controls (p < 0.001), the
      stimulation with AA (0.4 mm) determined LT-50% in all cases and controls.
      However, max-A% was higher in KS than in controls both after AA (0.2 mm) (65.61%
      vs. 46.30%, p = 0.002,) and after AA (0.4 mm) (96.43% vs. 81.04%, p < 0.001). 8
      iso-PGF2alpha and 11-dehydro-TXB2 were higher in KS than in controls (446.54
      pg/mg creatinine vs. 230.00 pg/mg creatinine, p < 0.001 and 1278.36 pg/mg
      creatinine vs. 595.08 pg/mg creatinine, p = 0.001, respectively) and AC-50%
      inversely correlated with 8-iso-PGF2alpha (rho = -0.548, p < 0.001) and with 11
      dehydro-TXB2 (rho = -0.523, p < 0.001). In a linear regression model, KS
      independently predicted a lower AC-50% (beta = -0.597, p < 0.001) and higher
      levels of 8-iso-PGF2alpha (beta = 0.709, p < 0.001) and 11-dehydro-TXB2 (beta =
      0.605, p < 0.001). In contrast, no correlation has been found between max-A%,
      testosterone and estradiol levels in KS. We observed increased platelet
      reactivity in KS. This might, at least in part, explain the increased thrombotic
      risk associated with this disease. 

PMID- 26216453
TI  - BioCluster: tool for identification and clustering of Enterobacteriaceae based on
      biochemical data.
AB  - Presumptive identification of different Enterobacteriaceae species is routinely
      achieved based on biochemical properties. Traditional practice includes manual
      comparison of each biochemical property of the unknown sample with known
      reference samples and inference of its identity based on the maximum similarity
      pattern with the known samples. This process is labor-intensive, time-consuming,
      error-prone, and subjective. Therefore, automation of sorting and similarity in
      calculation would be advantageous. Here we present a MATLAB-based graphical user
      interface (GUI) tool named BioCluster. This tool was designed for automated
      clustering and identification of Enterobacteriaceae based on biochemical test
      results. In this tool, we used two types of algorithms, i.e., traditional
      hierarchical clustering (HC) and the Improved Hierarchical Clustering (IHC), a
      modified algorithm that was developed specifically for the clustering and
      identification of Enterobacteriaceae species. IHC takes into account the
      variability in result of 1-47 biochemical tests within this Enterobacteriaceae
      family. This tool also provides different options to optimize the clustering in a
      user-friendly way. Using computer-generated synthetic data and some real data, we
      have demonstrated that BioCluster has high accuracy in clustering and identifying
      enterobacterial species based on biochemical test data. This tool can be freely
      downloaded at http://microbialgen.du.ac.bd/biocluster/. 

PMID- 26216454
TI  - Differential capacity of human interleukin-4 and interferon-alpha monocyte
      derived dendritic cells for cross-presentation of free versus cell-associated
      antigen.
AB  - Dendritic cells (DC) vaccination is a potent therapeutic approach for inducing
      tumor-directed immunity, but challenges remain. One of the particular interest is
      the induction of an immune response targeting multiple (unknown) tumor-associated
      antigens (TAA), which requires a polyvalent source of TAA. Previously, we
      described the preferred use of apoptotic cell-derived blebs over the larger
      apoptotic cell remnants, as a source of TAA for both in situ loading of skin
      resident DC and in vitro loading of monocyte-derived DC (MoDC). Recent reports
      suggest that MoDC cultured in the presence of GM-CSF supplemented with IFNalpha
      (IFNalpha MoDC), as compared to IL-4 (IL-4 MoDC), have an increased capacity to
      cross-present antigen to CD8(+) T cells. As culture conditions, maturation
      methods and antigen sources differ between the conducted studies, we analyzed the
      functional differences between IL-4 MoDC and IFNalpha MoDC, loaded with blebs, in
      a head-to-head comparison using commonly used protocols. Our data show that both
      MoDC types are potent (cross-) primers of CD8(+) T cells. Whereas IFNalpha MoDC
      were more potent in their capacity to cross-present a 25-mer MART-1 synthetic
      long peptide (SLP) to a MART-1aa26-35 recognizing CD8(+) T cell line, IL-4 MoDC
      proved more potent cross-primers of antigen-specific CD8(+) T cells when loaded
      with blebs. The latter is likely due to the observed greater capacity of IL-4
      MoDC to ingest apoptotic blebs. In conclusion, our data indicate the use of
      IFNalpha MoDC over IL-4 MoDC in the context of DC vaccination with SLP, whereas
      IL-4 MoDC are preferred for vaccination with bleb-derived antigens. 

PMID- 26216455
TI  - Differentiation of pleomorphic adenoma and Warthin's tumour of the salivary
      gland: is long-to-short diameter ratio a useful parameter?
AB  - AIM: To determine the utility of the long-to-short diameter ratio (L/S ratio) and
      other sonographic features in the differentiation of pleomorphic adenoma (PA) and
      Warthin's tumour (WT) of the salivary gland. MATERIAL AND METHODS: From 2003 to
      2013, 100 patients with 100 PAs and WTs were included in this ethics committee
      approved retrospective study. For each lesion, B-mode sonographic and colour
      Doppler images were obtained and the L/S ratios were calculated. Surgical
      excision and histopathological examination were accomplished in all cases.
      Differences between the L/S ratio and other sonographic features for PA and WT
      were evaluated. RESULTS: Of the 100 salivary tumours, 80 were located in the
      parotid (37 PAs and 43 WTs), and 20 were in the submandibular gland (19 PAs and
      one WT). In the parotid, the L/S ratio was 1.38+/-0.21 for PA and 1.73+/-0.46 for
      WT. The L/S ratio of the WTs was higher than that of the PAs (p<0.001). Applying
      a cut-off of 1.519, the sensitivity, specificity, and accuracy for
      differentiation of PA and WT in the parotid were 69.8%, 81.1%, and 75%,
      respectively; however, the accuracy dropped to 42.9% in diagnosing masses with
      >=50% macroscopic cystic structures. When those masses were excluded, the
      accuracy rose to 78.1%. CONCLUSIONS: The L/S ratio when used with other
      ultrasound features aids differentiation between PA and WT in the parotid gland;
      however, masses with macroscopic cystic structures >=50% should not be judged by
      this parameter.

PMID- 26216456
TI  - Role of Streptococcus uberis adhesion molecule in the pathogenesis of
      Streptococcus uberis mastitis.
AB  - Adherence to and internalization into mammary epithelial cells are central
      mechanisms in the pathogenesis of S. uberis mastitis. Through these pathogenic
      strategies, S. uberis reaches an intracellular environment where humoral host
      defenses and antimicrobials in milk are essentially ineffective, thus allowing
      persistence of this pathogen in the mammary gland. We reported that S. uberis
      expresses a surface adhesion molecule (SUAM) that has affinity for lactoferrin
      (LF) and a central role adherence to and internalization of S. uberis into bovine
      mammary epithelial cells. To define the role of SUAM in the pathogenesis of S.
      uberis mastitis, we created a sua gene deletion mutant clone of S. uberis UT888
      (Deltasua S. uberis UT888) unable to express SUAM. When tested in vitro, Deltasua
      S. uberis UT888 was defective in adherence to and internalization into bovine
      mammary epithelial cells. To prove that the absence of SUAM reduces bacterial
      attachment, subsequent colonization and infection of bovine mammary glands, the
      wild type S. uberis UT888 and its isogenic Deltasua S. uberis UT888 were infused
      into mammary quarters of dairy cows. Results showed that fewer mammary glands
      infused with Deltasua S. uberis UT888 become infected than those infused with the
      isogenic parental strain. Furthermore, mammary glands infused with Deltasua S.
      uberis UT888 had less severe clinical symptoms as compared to those infused with
      the isogenic parental strain. These results suggest that the SUAM mutant clone
      was less virulent than the isogenic parental strain which further substantiates
      the role of SUAM in the pathogenesis of S. uberis mastitis. 

PMID- 26216457
TI  - Mastitis in sheep--The last 10 years and the future of research.
AB  - Bacterial mastitis is a significant welfare and financial problem in sheep
      flocks. This paper reviews the recently published literature, including
      publications that highlight the significance and virulence factors of the causal
      agents, especially Staphylococcus aureus and Mannheimia haemolytica, the primary
      causes of the disease. Research has also contributed to the understanding of risk
      factors, including genetic susceptibility of animals to infections, supporting
      future strategies for sustainable disease control. Pathogenetic mechanisms,
      including the role of the local defenses in the teat, have also been described
      and can assist formulation of strategies that induce local immune responses in
      the teat of ewes. Further to well-established diagnostic techniques, i.e.,
      bacteriological tests and somatic cell counting, advanced methodologies, e.g.,
      proteomics technologies, will likely contribute to more rapid and accurate
      diagnostics, in turn enhancing mastitis control efforts. 

PMID- 26216458
TI  - Sex, drugs and pain control.

PMID- 26216459
TI  - The binding solution?

PMID- 26216460
TI  - Removing synaptic brakes on learning.

PMID- 26216461
TI  - Reassessing VMPFC: full of confidence?

PMID- 26216462
TI  - The RNAs of ALS.

PMID- 26216463
TI  - Investigating the effectiveness of technologies applied to assist seniors: A
      systematic literature review.
AB  - BACKGROUND: Recently, a number of Information and Communication Technologies have
      emerged with the aim to provide innovative and efficient ways to help seniors in
      their daily life and to reduce the cost of healthcare. Studies have been
      conducted to introduce an assistive technology to support seniors and to
      investigate the acceptance of these assistive technologies; however, research
      illustrating the effectiveness of assistive technologies is scant. METHOD: This
      study undertakes a systematic literature review of ScienceDirect, PubMed,
      ProQuest and IEEE Explore databases to investigate current empirical studies on
      the assistive technologies applied in aged care. Our systematic review of an
      initial set of 2035 studies published from 2000 to 2014 examines the role of
      assistive technologies in seniors' daily lives, from enhancements in their
      mobility to improvements in the social connectedness and decreases in readmission
      to hospitals. RESULTS: This study found eight key issues in aged care that have
      been targeted by researchers from different disciplines (e.g., ICT, health and
      social science), namely, dependent living, fall risk, chronic disease, dementia,
      social isolation, depression, poor well-being, and poor medication management.
      This paper also identified the assistive technologies that have been proposed to
      overcome those problems, and we categorised these assistive technologies into six
      clusters, namely, general ICT, robotics, telemedicine, sensor technology,
      medication management applications, and video games. In addition, we analyzed the
      effectiveness of the identified technologies and noted that some technologies can
      change and enhance seniors' daily lives and relieve their problems. Our analysis
      showed a significant growth in the number of publications in this area in the
      past few years. It also showed that most of the studies in this area have been
      conducted in North America. CONCLUSION: Assistive technologies are a reality and
      can be applied to improve quality of life, especially among older age groups.
      This study identified various assistive technologies proposed by ICT researchers
      to assist the elderly. We also identified the effectiveness of the proposed
      technologies. This review shows that, although assistive technologies have been
      positively evaluated, more studies are needed regarding the outcome and
      effectiveness of these technologies.

PMID- 26216464
TI  - Modulation of the transient outward current (Ito) in rat cardiac myocytes and
      human Kv4.3 channels by mefloquine.
AB  - The antimalarial drug mefloquine, is known to be a potassium channel blocker,
      although its mechanism of action has not being elucidated and its effects on the
      transient outward current (Ito) and the molecular correlate, the Kv4.3 channel
      has not being studied. Here, we describe the mefloquine-induced inhibition of the
      rat ventricular Ito and of CHO cells co-transfected with human Kv4.3 and its
      accessory subunit hKChIP2C by whole-cell voltage-clamp. Mefloquine inhibited rat
      Ito and hKv4.3+KChIP2C currents in a concentration-dependent manner with a
      limited voltage dependence and similar potencies (IC50=8.9MUM and 10.5MUM for
      cardiac myocytes and Kv4.3 channels, respectively). In addition, mefloquine did
      not affect the activation of either current but significantly modified the hKv4.3
      steady-state inactivation and recovery from inactivation. The effects of this
      drug was compared with that of 4-aminopyridine (4-AP), a well-known potassium
      channel blocker and its binding site does not seem to overlap with that of 4-AP. 

PMID- 26216465
TI  - The Critical Effect of Niobium Doping on the Formation of Mesostructured TiO2 :
      Single-Crystalline Ordered Mesoporous Nb-TiO2 and Plate-like Nb-TiO2 with Ordered
      Mesoscale Dimples.
AB  - Highly ordered mesoporous niobium-doped TiO2 with a single-crystalline framework
      was prepared by using silica colloidal crystals with ca. 30 nm in diameter as
      templates. The preparation of colloidal crystals composed of uniform silica
      nanoparticles is a key to obtain highly ordered mesoporous Nb-doped TiO2 . The
      XPS measurements of Nb-doped TiO2 showed the presence of Nb(5+) and
      correspondingly Ti(3+) . With the increase in the amount of doped Nb, the
      crystalline phase of the product was converted from rutile into anatase, and the
      lattice spacings of both rutile and anatase phases increased. Surprisingly, the
      increase in the amount of Nb led to the formation of plate-like TiO2 with dimpled
      surfaces on one side, which was directly replicated from the surfaces of the
      colloidal silica crystals. 

PMID- 26216466
TI  - Stories of MDM: Helping Patients and Clinicians Manage Uncertainty during
      Clinical Care.

PMID- 26216467
TI  - Whole transcriptome profiling of the vernalization process in Lilium longiflorum
      (cultivar White Heaven) bulbs.
AB  - BACKGROUND: Vernalization is an obligatory requirement of extended exposure to
      low temperatures to induce flowering in certain plants. It is the most important
      factor affecting flowering time and quality in Easter lily (Lilium longiflorum).
      Exposing the bulbs to 4  degrees C gradually decreases flowering time up to 50%
      compared to non-vernalized plants. We aim to understand the molecular regulation
      of vernalization in Easter lily, for which we characterized the global expression
      in lily bulb meristems after 0, 2, 5, 7 and 9 weeks of incubation at 4  degrees
      C. RESULTS: We assembled de-novo a transcriptome which, after filtering, yielded
      121,572 transcripts and 42,430 genes which hold 15,414 annotated genes, with up
      to 3,657 GO terms. This extensive annotation was mapped to the more general GO
      slim plant with a total of 94 terms. The response to cold exposure was summarized
      in 6 expression clusters, providing useful patterns for dissecting the dynamics
      of vernalization in lily. The functional annotation (GO and GO slim plant) was
      used to group transcripts in gene sets. Analysis of these gene sets and profiles
      revealed that most of the enriched functions among genes up-regulated by cold
      exposure were related to epigenetic processes and chromatin remodeling. Candidate
      vernalization genes in lily were selected based on their sequence similarity to
      known regulators of flowering in other species. CONCLUSIONS: We present a
      detailed analysis of gene expression dynamics during vernalization in Lilium,
      covering several time points and accounting for biological variation by the use
      of replicates. The resulting collection of transcripts and novel isoforms
      provides a useful resource for studying the changes occurring during
      vernalization at a fine level. The selected potential candidate genes can shed
      light on the regulation of this process.

PMID- 26216468
TI  - The 'island effect' in terrestrial global change experiments: a problem with no
      solution?
AB  - Most of the currently experienced global environmental changes (rising
      atmospheric CO2 concentrations, warming, altered amount and pattern of
      precipitation, and increased nutrient load) directly or indirectly affect
      ecosystem surface energy balance and plant transpiration. As a consequence, the
      relative humidity of the air surrounding the vegetation changes, thus creating a
      feedback loop whose net effect on transpiration and finally productivity is not
      trivial to quantify. Forcedly, in any global change experiment with the above
      drivers, we can only treat small plots, or 'islands', of vegetation. This means
      that the treated plots will likely experience the ambient humidity conditions
      influenced by the surrounding, non-treated vegetation. Experimental assessments
      of global change effects will thus systematically lack modifications originating
      from these potentially important feedback mechanisms, introducing a bias of
      unknown magnitude in all measurements of processes directly or indirectly
      depending on plant transpiration. We call this potential bias the 'island
      effect'. Here, we discuss its implications in various global change experiments
      with plants. We also suggest ways to complement experiments using modelling
      approaches and observational studies. Ultimately, there is no obvious solution to
      deal with the island effect in field experiments and only models can provide an
      estimate of modification of responses by these feedbacks. However, we suggest
      that increasing the awareness of the island effect among both experimental
      researchers and modellers will greatly improve the interpretation of vegetation
      responses to global change. 

PMID- 26216469
TI  - Molecular characterization of a mutation affecting abscisic acid biosynthesis and
      consequently stomatal responses to humidity in an agriculturally important
      species.
AB  - Mutants deficient in the phytohormone abscisic acid (ABA) have been instrumental
      in determining not only the biosynthetic pathway for this hormone, but also its
      physiological role in land plants. The wilty mutant of Pisum sativum is one of
      the classical, well-studied ABA-deficient mutants; however, this mutant remains
      uncharacterized at a molecular level. Using a candidate gene approach, we show
      that the wilty mutation affects the xanthoxin dehydrogenase step in ABA
      biosynthesis. To date, this step has only been represented by mutants in the ABA2
      gene of Arabidopsis thaliana. Functional ABA biosynthesis appears to be critical
      for normal stomatal responses to changes in humidity in angiosperms, with wilty
      mutant plants having no increase in foliar ABA levels in response to a doubling
      in vapour pressure deficit, and no closure of stomata. Phylogenetic analysis of
      the ABA2 gene family from diverse land plants indicates that an ABA-biosynthesis
      specific short-chain dehydrogenase (ABA2) evolved in the earliest angiosperms.
      The relatively recent origin of specificity in this step has important
      implications for both the evolution of ABA biosynthesis and action in land
      plants. 

PMID- 26216470
TI  - Clindamycin-induced hypersensitivity reaction.
AB  - Drug-induced anaphylaxis is an unpredictable adverse reaction. Although it may
      occur with any medication, antibiotics induce more cases of anaphylaxis than any
      other medication class with most cases being induced by beta-lactam antibiotics.
      Clindamycin is an antibiotic with good gram-positive and anaerobe coverage which
      is often used in patients with beta-lactam allergies. We report the case of a 46
      year-old female who experienced anaphylaxis after a dose of intravenous (IV)
      clindamycin. Following treatment with methylprednisolone, epinephrine,
      diphenhydramine, and albuterol, the patient stabilized. The patient's score on
      the Naranjo's algorithm was 8 (probable); a score of 9 (definite) limited only by
      absence of drug re-challenge. To our knowledge, this is the first report of a
      clindamycin-induced anaphylaxis where the patient was not exposed to any other
      agent that may have triggered the response, the first case in the United States,
      and only the third documented case in the literature. Clinicians should be aware
      of the potential for drug-induced anaphylaxis in all medications. 

PMID- 26216472
TI  - Optimizing equivalence-based instruction: Effects of training protocols on
      equivalence class formation.
AB  - Two experiments evaluated the effects of the simple-to-complex and simultaneous
      training protocols on the formation of academically relevant equivalence classes.
      The simple-to-complex protocol intersperses derived relations probes with
      training baseline relations. The simultaneous protocol conducts all training
      trials and test trials in separate portions of the protocol. In Experiments 1 and
      2, participants formed 4 3- and 4-member neuroanatomy classes, respectively. When
      trained with the simple-to-complex protocol, 100% of participants immediately
      formed the 3- or 4-member classes. When trained with the simultaneous protocol,
      the 3- and 4-member classes were formed immediately by 75% and 42% of
      participants, respectively. Thus, the immediate emergence of equivalence classes
      was an interactive function of training protocol and class size. The remaining
      participants eventually formed classes after a few cycles of retraining. The
      incorporation of these training and testing parameters could optimize the use of
      equivalence-based instruction for teaching college-level course content. 

PMID- 26216473
TI  - Identification of Tyrosine-Phosphorylated Proteins Upregulated during Epithelial
      Mesenchymal Transition Induced with TGF-beta.
AB  - The epithelial-to-mesenchymal transition (EMT) is a unique process for the
      phenotypic changes of tumor cells characterized by a transition from polarized
      rigid epithelial cells to migrant mesenchymal cells, thus conferring the ability
      of tumor invasion and metastasis. A major challenge in the treatment of lung
      adenocarcinoma is to identify early stage patients at a high risk of recurrence
      or metastasis, thereby permitting the best therapeutic strategy and prognosis. In
      this study, we used a transforming growth factor-beta (TGF-beta)-induced EMT
      model to quantitatively identify protein tyrosine phosphorylation during the
      course of EMT in relation to malignant characteristics of lung adenocarcinoma
      cells. We performed relative quantitation analysis of tyrosine-phosphorylated
      peptides in TGF-beta-treated and -untreated lung adenocarcinoma cells and
      identified tyrosine-phosphorylated proteins that were upregulated in TGF-beta
      treated cells. These include tensin-1 (TNS1) phosphorylated on Y1404, hepatocyte
      growth factor receptor (c-Met) phosphorylated on Y1234, and NT-3 growth factor
      receptor (TrkC) phosphorylated on Y516. We also found that these protein
      phosphorylation profiles were specifically observed in tissue samples of patients
      with poor prognostic lung adenocarcinoma. Tyrosine phosphorylations of these
      proteins represent possible candidates of prognostic prediction markers for lung
      adenocarcinoma. 

PMID- 26216474
TI  - Microelectrode bioimpedance analysis distinguishes basal and claudin-low subtypes
      of triple negative breast cancer cells.
AB  - Triple negative breast cancer (TNBC) is highly aggressive and has a poor
      prognosis when compared to other molecular subtypes. In particular, the claudin
      low subtype of TNBC exhibits tumor-initiating/cancer stem cell like properties.
      Here, we seek to find new biomarkers to discriminate different forms of TNBC by
      characterizing their bioimpedance. A customized bioimpedance sensor with four
      identical branched microelectrodes with branch widths adjusted to accommodate
      spreading of individual cells was fabricated on silicon and pyrex/glass
      substrates. Cell analyses were performed on the silicon devices which showed
      somewhat improved inter-electrode and intra-device reliability. We performed
      detailed analysis of the bioimpedance spectra of four TNBC cell lines, comparing
      the peak magnitude, peak frequency and peak phase angle between claudin-low TNBC
      subtype represented by MDA-MB-231 and Hs578T with that of two basal cells types,
      the TNBC MDA-MB-468, and an immortalized non-malignant basal breast cell line,
      MCF-10A. The claudin-low TNBC cell lines showed significantly higher peak
      frequencies and peak phase angles than the properties might be useful in
      distinguishing the clinically significant claudin-low subtype of TNBC.

PMID- 26216471
TI  - Region-Dependent Role of Cell-Penetrating Peptides in Insulin Absorption Across
      the Rat Small Intestinal Membrane.
AB  - We have reported that the cell-penetrating peptide (CPP) penetratin acts as a
      potential absorption enhancer in oral insulin delivery systems and that this
      action occurs through noncovalent intermolecular interactions. However, the
      region-dependent role of CPPs in intestinal insulin absorption has not been
      clarified. To identify the intestinal region where CPPs have the most effect in
      increasing insulin absorption, the region-dependent action of penetratin was
      investigated using in situ closed intestinal loops in rats. The order of the
      insulin area under the insulin concentration-time curve (AUC) increase effect by
      L-penetratin was ileum > jejunum > duodenum > colon. By contrast, the AUC order
      after coadministration of insulin with D-penetratin was colon > duodenum >=
      jejunum and ileum. We also compared the effects of the L- and D-forms of
      penetratin, R8, and PenetraMax on ileal insulin absorption. Along with the CPPs
      used in this study, L- and D-PenetraMax produced the largest insulin AUCs. An
      absorption study using ilea pretreated with CPPs showed that PenetraMax had no
      irreversible effect on the intestinal epithelial membrane. The degradation of
      insulin in the presence of CPPs was assessed in rat intestinal enzymatic fluid.
      The half-life (t 1/2) of insulin increased from 14.5 to 23.7 and 184.7 min in the
      presence of L- and D-PenetraMax, respectively. These enzymatic degradation
      resistant effects might contribute partly to the increased ileal absorption of
      insulin induced by D-PenetraMax. In conclusion, this study demonstrated that the
      ability of the L- and D-forms of penetratin to increase intestinal insulin
      absorption was maximal in the ileum and the colon, respectively, and that D
      PenetraMax is a powerful but transient enhancer of oral insulin absorption. 

PMID- 26216475
TI  - Longitudinal associations among maternal communication and adolescent
      posttraumatic stress symptoms after cancer diagnosis.
AB  - OBJECTIVE: The purpose of this study was to prospectively examine adolescent and
      maternal posttraumatic stress symptoms (PTSS) and maternal communication from
      time near cancer diagnosis to 12-month follow-up to identify potential risk
      factors for adolescent PTSS. METHODS: Forty-one adolescents with cancer (10-17
      years, 54% female) and their mothers self-reported PTSS at T1 (two months after
      cancer diagnosis) and T3 (1-year follow-up). At T2 (3 months after T1), mother
      adolescent dyads were videotaped discussing cancer, and maternal communication
      was coded with macro (harsh and withdrawn) and micro (solicits and validations)
      systems. RESULTS: Adolescent PTSS at T1 was associated with adolescent PTSS at
      T3. Greater maternal PTSS at T1 predicted greater harsh maternal communication at
      T2. There was an indirect effect of maternal PTSS at T1 on adolescent PTSS at T3
      through maternal validations at T2. CONCLUSIONS: Findings underscore the
      importance of maternal PTSS, maternal communication, and subsequent adolescent
      PTSS over the course of treatment of childhood cancer. Copyright (c) 2015 John
      Wiley & Sons, Ltd. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26216476
TI  - Multivariate analysis of traditional pig management practices and their potential
      impact on the spread of infectious diseases in Corsica.
AB  - Corsica is a French Mediterranean island with traditional extensive pig farming
      oriented towards the production of high quality cured meat products. The
      increasing success of these cured products in continental Europe has triggered
      the development and organisation of an extensive pig farming industry. However,
      these pig farming practices have seldom been described and analysed to understand
      the potential risk of introduction and spread of infectious diseases. We
      conducted a cross-sectional study in Corsica in 2013 to characterise the main pig
      management practices and to identify groups of farms with similar practices and
      therefore homogeneous risk of introduction and spread of infectious diseases. We
      interviewed 68 pig farmers and investigated different farm management practices
      which could lead to contact between herds, such as trading animals, sharing
      pastures, feed and reproduction management (direct contacts), slaughtering and
      carcass waste management, and contacts with people and vehicles (indirect
      contacts). The practices were described and the farms grouped by multiple factor
      and hierarchical clustering analyses. Results revealed interesting patterns in
      the introduction and spread of infectious disease, such as the seasonality of pig
      production, the potential local spread of diseases in pastures due to the
      presence of free-ranging boars, carcasses, and animal waste. Multivariate
      analyses identified four groups of farms with different levels of risk of the
      spread of infectious disease, illustrating changes in farmers' customs from free
      range uncontrolled farming systems to more controlled systems aimed at the
      production of high quality pork products. These results will be useful to more
      realistically simulate the spread of infectious diseases among Corsican pig farms
      and highlight the need for awareness raising campaigns among the stakeholders to
      reduce risky practices. 

PMID- 26216477
TI  - Effect of feeding guanidinoacetic acid and L-arginine on the fertility rate and
      sperm penetration in the perivitelline layer of aged broiler breeder hens.
AB  - Two experiments were conducted to evaluate the effects of feeding guanidinoacetic
      acid (GAA) and L-arginine (ARG) on fertility and sperm penetration (SP) rate of
      broiler breeder hens. In the first experiment, a total of 200 broiler breeder
      hens (Ross 308) aged 53 weeks were randomly allotted to four dietary treatments
      (0, 0.6, 1.2 and 1.8 g GAA/kg diet) with five replicates of 10 birds each. In the
      second experiment, 320 broiler breeder hens (Ross 308) were used from 53 to 62
      weeks of age in a 2 * 4 factorial arrangement (0 or 1.2 g GAA/kg diet along with
      0, 3, 6 or 9 g ARG/kg diet). The hens received a diet containing 2800 kcal ME/kg
      and 14% CP. Sixteen sexually mature Ross 308 breeder roosters (34 weeks old) were
      used to artificially inseminate the hens. Fertility of the hens was determined in
      61 and 62 weeks of age. The sperm penetration holes in the inner perivitelline
      layer (IPL) overlying the germinal disc were enumerated on days 3 and 7 following
      each insemination. Adding GAA to the breeder diet increased the number of SPs in
      the IPL and fertility in both experiments (p < 0.01). The interactive effect of
      ARG and GAA on the SP and fertility was significant. Supplementary ARG increased
      the SP rate in the IPL (p < 0.01). In conclusion, dietary supplementation of GAA
      and ARG might be potentially used to improve the fertility of broiler breeder
      hens at the later phase of the egg production period.

PMID- 26216478
TI  - The Alburnus benthopelagic fish species of the Western Balkan Peninsula: An
      assessment of their sustainable use.
AB  - In this study, we aimed to assess the population status of bleak (Alburnus spp.)
      over the Western Balkan Peninsula in terms of its sustainable use. A second
      objective was to determine key factors important for fishery management planning.
      Two different basins, continental (the Danube Basin and the Sava River sub-basin)
      and marine (the Adriatic and the Aegean Sea Basins) were examined. A
      sustainability assessment and factor analysis were conducted using the adjusted
      ESHIPPOfishing model, extended with additional socio-economic sub-elements, and
      the categorical principal components analysis (CATPCA), respectively. The results
      of the assessment revealed the bleak populations in the Danube Basin and the Sava
      River sub-basin to be highly sustainable. The population characteristics with
      abiotic and biotic factors were responsible for this status, while the influence
      of socio-economic factors was insignificant. The sustainability status of the
      bleak populations of the Mediterranean basin varied, with the populations from
      Ohrid and Skadar Lakes showing a high and those from Prespa and Dojran Lakes a
      medium status. Socio-economic factors with traditional fishing were the most
      important for the Mediterranean bleak populations. 

PMID- 26216479
TI  - Candida species epidemiology 2000-2013: a laboratory-based report.
AB  - OBJECTIVE: To describe a prospective laboratory-based surveillance of Candida
      species that were collected from different anatomical sites of patients admitted
      to the University of Malaya Medical Centre, Malaysia, from the year 2000 to 2013.
      METHODS: Conventional (culture, microscopic examination and carbohydrate
      assimilation test) and molecular (PCR amplification and DNA sequencing)
      techniques were used to identify Candida species. RESULTS: A total of 16 Candida
      species isolated from 34 392 clinical samples were from the oral cavity (oral
      swabs and throat swabs), blood, respiratory tract (sputum, tracheal secretions,
      nasopharyngeal aspirates, bronchoalveolar lavage), high vaginal swab, pus and
      urine. C. albicans (66.70%, 22 941/34 392), C. glabrata (11.71%, 4029/34 392), C.
      parapsilopsis (10.74%, 3692/34 392), C. tropicalis (9.19%, 3162/34 392) and C.
      krusei (1.15%, 396/34 392) were the five predominant Candida species. C. albicans
      was the predominant species isolated from the oral cavity, respiratory tract and
      high vaginal swab; while the Candida species isolated from blood, urine and pus
      were predominant non-albicans Candida. Uncommon Candida species, such as C.
      lusitaniae, C. haemulonii, C. humicola, Pichia ohmeri and C. ciferrii, were also
      isolated in this study. CONCLUSION: Our study expands the current knowledge of
      the epidemiology of non-invasive and invasive candidiasis in Malaysia. The
      variability of the Candida species distribution from different anatomical sites
      highlights the significance of local epidemiology in disease management and
      selection of antifungal agents.

PMID- 26216480
TI  - Impact of catheter ablation with remote magnetic navigation on procedural
      outcomes in patients with persistent and long-standing persistent atrial
      fibrillation.
AB  - BACKGROUND: The objectives of this study were to assess the procedural outcomes
      of persistent and long-standing persistent atrial fibrillation (PsAF and L-PsAF)
      ablation guided by remote magnetic navigation (RMN), and to detect factors
      predicting acute restoration of sinus rhythm (SR) by ablation with RMN. METHODS:
      A total of 313 patients (275 male, age 59 +/- 9.5 years) with PsAF (187/313) or L
      PsAF (126/313) undergoing ablation using RMN were included. Patients' disease
      history, pulmonary venous anatomy, left atrial (LA) volume, procedure time,
      mapping plus ablation time, radiofrequency (RF) ablation time, fluoroscopy time,
      radiation dose, and complications were assessed. Stepwise regression was used to
      predict which variable could best predict acute restoration from AF to SR by
      ablation. RESULTS: Compared to PsAF, procedure time and RF ablation time were
      significantly increased in patients with L-PsAF (P = 0.01 and P < 0.001,
      respectively). No major complications occurred during the procedures in either
      PsAF or L-PsAF patients. Fifty five of 313 patients converted directly to SR by
      ablation. Compared to L-PsAF, the rate of SR restoration was significantly higher
      in PsAF (21 vs 12%, P = 0.03). Stepwise regression analysis showed LA volume was
      the primary parameter affecting SR restoration (P = 0.01). The LA volume of
      patients without direct SR restoration by ablation was 24% greater than that of
      patients with SR restoration (P < 0.001). CONCLUSIONS: Catheter ablation using
      RMN is a safe and effective method for PsAF and L-PsAF. LA volume could be a
      predictor of direct restoration of SR from sustaining AF by ablation using RMN.

PMID- 26216481
TI  - Editorial.

PMID- 26216483
TI  - miR-218 is involved in the negative regulation of osteoclastogenesis and bone
      resorption by partial suppression of p38MAPK-c-Fos-NFATc1 signaling: Potential
      role for osteopenic diseases.
AB  - The increased osteoclastic activity accounts for pathological bone loss in
      diseases including osteoporosis. MicroRNAs are widely accepted to be involved in
      the regulation of osteopenic diseases. Recently, the low expression of miR-218
      was demonstrated in CD14(+) peripheral blood mononuclear cells (PBMCs) from
      patients with postmenopausal osteoporosis. However, its role and the underlying
      mechanism in osteoporosis are still undefined. Here, an obvious decrease in miR
      218 expression was observed during osteoclastogenesis under receptor activator of
      nuclear factor kappaB ligand (RANKL) stimulation, in both osteoclast precursors
      of bone marrow macrophages (BMMs) and RAW 264.7. Further analysis confirmed that
      overexpression of miR-218 obviously attenuated the formation of multinuclear
      mature osteoclasts, concomitant with the decrease in Trap and Cathepsin K levels,
      both the master regulators of osteoclastogenesis. Moreover, miR-218 up-regulation
      dramatically inhibited osteoclast precursor migration, actin ring formation and
      bone resorption. Mechanism assay demonstrated that miR-218 overexpression
      attenuated the expression of p38MAPK, c-Fos and NFATc1 signaling molecules.
      Following preconditioning with P79350, an agonist of p38MAPK, the inhibitor
      effect of miR-218 on osteoclastogenesis and bone-resorbing activity was
      strikingly ameliorated. Together, this study revealed a crucial role of miR-218
      as a negative regulator for osteoclastogenesis and bone resorption by suppressing
      the p38MAPK-c-Fos-NFATc1 pathway. Accordingly, this research will provide a
      promising therapeutic agent against osteopenic diseases including osteoporosis.

PMID- 26216484
TI  - Fast CPU-based Monte Carlo simulation for radiotherapy dose calculation.
AB  - Monte-Carlo (MC) simulations are considered to be the most accurate method for
      calculating dose distributions in radiotherapy. Its clinical application,
      however, still is limited by the long runtimes conventional implementations of MC
      algorithms require to deliver sufficiently accurate results on high resolution
      imaging data. In order to overcome this obstacle we developed the software
      package PhiMC, which is capable of computing precise dose distributions in a sub
      minute time-frame by leveraging the potential of modern many- and multi-core CPU
      based computers. PhiMC is based on the well verified dose planning method (DPM).
      We could demonstrate that PhiMC delivers dose distributions which are in
      excellent agreement to DPM. The multi-core implementation of PhiMC scales well
      between different computer architectures and achieves a speed-up of up to
      37[Formula: see text] compared to the original DPM code executed on a modern
      system. Furthermore, we could show that our CPU-based implementation on a modern
      workstation is between 1.25[Formula: see text] and 1.95[Formula: see text] faster
      than a well-known GPU implementation of the same simulation method on a NVIDIA
      Tesla C2050. Since CPUs work on several hundreds of GB RAM the typical GPU memory
      limitation does not apply for our implementation and high resolution clinical
      plans can be calculated. 

PMID- 26216485
TI  - Anaerobic Degradation Pathway of the Novel Chiral Insecticide Paichongding and
      Its Impact on Bacterial Communities in Soils.
AB  - To comprehensively understand anaerobic degradation of the novel cis
      nitromethylene neonicotinoid insecticide Paichongding (IPP) and its impacts on
      microbial communities in anaerobic soils, we investigated IPP degradation
      characteristics, kinetics, and pathway in four different soils. The bacterial
      community in response to the application of IPP using pyrosequencing of 16S rRNA
      gene amplicons was also studied. The removal ratio of IPP stereoisomers (RR-IPP,
      SS-IPP, RS-IPP, and SR-IPP) reached >90% at 60 days after IPP treatment (DAT) in
      yellow loam soil (F) and paddy field on desalting muddy polder (C), whereas the
      degradation ratios of RR-IPP and SS-IPP were <30% at 60 DAT in Huangshi soil (J)
      and yellow paddy soil (H). The results showed that the anaerobic degradation rate
      of IPP and its stereoisomers was strongly affected by soil physical-chemical
      characteristics. Furthermore, on the basis of the six metabolites (M1-M6)
      identified by LC-MS/MS and their behavior, the anaerobic degradation pathway of
      IPP in soils was proposed. Biodegradation of IPP involved continuous biocatalytic
      reactions such as nitro reduction and elimination, hydrolysis, demethyl, and
      ether cleavage reactions. A higher richness of operational taxonomic units (OTUs)
      was found in soils without IPP application than in soils with IPP application.
      Both the rarefaction curves and Shannon-Wiener diversity index in anaerobic soils
      had significant difference after IPP application, and the community composition
      also differed at both the phyla and genus levels. 

PMID- 26216487
TI  - Transcriptional profiling of chronic clinical hepatic schistosomiasis japonica
      indicates reduced metabolism and immune responses.
AB  - Schistosomiasis is a significant cause of human morbidity and mortality. We
      performed a genome-wide transcriptional survey of liver biopsies obtained from
      Chinese patients with chronic schistosomiasis only, or chronic schistosomiasis
      with a current or past history of viral hepatitis B. Both disease groups were
      compared with patients with no prior history or indicators of any liver disease.
      Analysis showed in the main, downregulation in gene expression, particularly
      those involved in signal transduction via EIF2 signalling and mTOR signalling, as
      were genes associated with cellular remodelling. Focusing on immune associated
      pathways, genes were generally downregulated. However, a set of three genes
      associated with granulocytes, MMP7, CLDN7, CXCL6 were upregulated. Differential
      gene profiles unique to schistosomiasis included the gene Granulin which was
      decreased despite being generally considered a marker for liver disease, and
      IGBP2 which is associated with increased liver size, and was the most upregulated
      gene in schistosomiasis only patients, all of which presented with hepatomegaly.
      The unique features of gene expression, in conjunction with previous reports in
      the murine model of the cellular composition of granulomas, granuloma formation
      and recovery, provide an increased understanding of the molecular immunopathology
      and general physiological processes underlying hepatic schistosomiasis. 

PMID- 26216489
TI  - Identification of a naturally processed HLA-Cw7-binding peptide that cross-reacts
      with HLA-A24-restricted ovarian cancer-specific CTLs.
AB  - Here, we describe an human leukocyte antigen (HLA)-A*24:02-restricted cytotoxic T
      lymphocyte (CTL) clone, 1G3, established from naive CD8(+) T-lymphocytes obtained
      from a healthy donor stimulated with HLA-modified TOV21G, an ovarian cancer cell
      line. The 1G3 clone responds not only to ovarian cancer cells in the context of
      HLA-A*24:02 but also to allogeneic HLA-Cw*07:02 molecules through cross-reactive
      T-cell receptor recognition. Expression screening using a complementary DNA
      library constructed from TOV21G messenger RNA revealed that this alloreactivity
      was mediated through the nine-mer peptide VRTPYTMSY, derived from RNA-binding
      motif protein 4. To our knowledge, this study presents the first example of the
      allorecognition of an HLA-Cw molecule by HLA-A-restricted T-cells, thereby
      revealing a naturally processed epitope peptide. These findings provide the
      structural bases for the allorecognition of human T-cells. In addition, this
      study suggests that unexpected alloresponses occur in certain HLA combinations,
      and further study is needed to understand the mechanisms of alloreactivity for
      better prediction of alloresponses in clinical settings. 

PMID- 26216490
TI  - The Value of Occlusion in Dentistry: A Clinical Report Showing the Correction of
      an Anterior Reverse Articulation with Selective Occlusal Adjustment.
AB  - The subject of occlusion has been deemphasized by academia over the last 30
      years. This marginalization in turn has negatively impacted recent graduates who
      are largely unfamiliar with the use of occlusal adjustment by selective reshaping
      as a treatment modality. Use of proper occlusal therapy enables clinicians to
      more effectively help patients recover from parafunctional wear of the anterior
      and posterior teeth. In addition, familiarity with this field enhances the
      correction of progressive posterior and anterior reverse articulations. This
      article aims to highlight the importance of occlusal principles in treatment
      planning. In addition, we illustrate the benefits of occlusal adjustment by using
      a conservative technique, selective reshaping, as an option to correct anterior
      reverse articulation in a 20-year-old patient. The knowledge of occlusal
      principles enhances diagnosis of malocclusion in the development of a treatment
      plan. When properly employed, the technique of occlusal adjustment by selective
      reshaping may be used to correct an adaptive anterior reverse articulation with a
      high degree of predictability for select patients. 

PMID- 26216491
TI  - Symptom perception and asthma control.
AB  - OBJECTIVES: Asthma control is the goal of asthma management. The perception of
      asthma symptoms represents a cornerstone aspect in this issue. The visual
      analogue scale (VAS) has been proposed as a useful tool for assessing respiratory
      symptoms perception. The present cross-sectional real-life study investigated
      whether VAS assessment of asthma symptoms perception could predict asthma control
      level. METHODS: This cross-sectional study included a total of 370 (153 males,
      mean age 39.9 years) patients with asthma. Perception of asthma symptoms was
      assessed by VAS; clinical examination, lung function, fraction of exhaled nitric
      oxide (FeNO) measurement, Asthma Control Test (ACT) and Hospital Anxiety
      Depression Scale questionnaires were also evaluated. RESULTS: Asthma was well
      controlled in 47% of patients. Considering most of the evaluated parameters,
      there were significant differences among patients with well-controlled, partly
      controlled and uncontrolled asthma. VAS values were significantly (p < 0.001)
      different considering the asthma control level. VAS score were significantly
      related with ACT scores (p < 0.001). A VAS <6 was able to reliably predict
      uncontrolled asthma (area under the curve: 0.74; odds ratio: 5.16). CONCLUSION:
      The present real-life study demonstrates that asthma symptoms assessment by VAS
      might be useful for approximately predicting uncontrolled asthma in particular
      conditions, such as at home or at the general practitioner's office.

PMID- 26216492
TI  - Normative data for the ACE-R in an Italian population sample.
AB  - The Addenbrooke's Cognitive Examination Revised (ACE-R) is a brief cognitive
      screening instrument also proposed to detect mild cognitive impairment, a high
      risk condition for Alzheimer's disease and other forms of dementia. In this
      study, we report normative data on the ACE-R-Italian version, collected on a
      sample of 264 Italian healthy subjects aging between 60 and 93 years, and with a
      formal education from 1 to 19 years. The global normal cognition was established
      in accordance with the Italian version of the Mini-Mental State Examination score
      and with exclusion criteria derived by a consensus process. Linear regression
      analysis was performed to evaluate the effect of age, gender, and education on
      the ACE-R total performance score. We provide correction grids to adjust raw
      scores and equivalent scores with cut-off value to allow comparison between ACE-R
      performance and others neuropsychological test scores that can be administered to
      the same subject.

PMID- 26216493
TI  - Neuroscience, the microscope and the truth: personal philosophical considerations
      by a professor emeritus of neuropathology and neurology.
AB  - The article starts from the conception that the world is introduced in our mind
      though linguistic categories and that between us and the world there is always
      the language. This implies that to denominate still means to know. The visual
      pathway is described from the retina to the occipital cortex with the related
      phenomena of the recognition of the external world, through the Gestalt
      psychology, the reciprocal influence of sign/receptor, the mental images or
      patterns, the cognition, the conscience and memory. As an example, the microscope
      is presented as a tool for exploring the external world. The scientific
      objectivity is given by the dialectic with the scientific inter-subjectivity
      that, if abandoned, may give origin to mistakes or dangerous ideologies. The
      scientific truth is not absolute and perennial, but contingent and temporary and
      it is validated by the epochal parameters. The features outlined may apply to
      scientific research, clinical reasoning and also to the general behavior. 

PMID- 26216495
TI  - N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) Measurements Until a 30%
      Reduction Is Attained During Acute Decompensated Heart Failure Admissions and
      Comparison With Discharge NT-proBNP Levels: Implications for In-Hospital Guidance
      of Treatment.
AB  - BACKGROUND: A >30% N-terminal pro-B-type natriuretic peptide (NT-proBNP)
      reduction at discharge in acute decompensated heart failure (ADHF) predicts a
      favorable prognosis. To study the feasibility of guiding ADHF treatment by
      measuring NT-proBNP well before discharge, we assessed at which moment during
      hospitalization patients attain a NT-proBNP reduction of >30% (target) and
      whether this target is still attained at discharge. METHODS: Twenty-five
      consecutive ADHF patients with NT-proBNP >1,700 ng/L were included (original
      cohort). NT-proBNP was measured daily until the target was attained, at clinical
      stability, and at discharge and was analyzed as percentages of patients on
      target. For comparison purposes, the same analysis was performed in individual
      patient data from 2 other ADHF cohorts (42 and 111 patients, respectively), in
      which NT-proBNP was measured from admission to day 3 and at discharge. RESULTS:
      In the original cohort of 25 patients (median age 70 years, 40% male), the
      cumulative percentage of patients attaining the target increased gradually during
      admission to 22 patients (88%) in a median of 3 days (interquartile range 2-5).
      In the comparison cohorts, a similar course was observed in patients attaining
      the target before discharge. Compared with levels measured at days 2 and 3,
      rebound NT-proBNP increases to levels off-target at discharge were seen in up to
      33% of patients in the original and comparison cohorts. CONCLUSION: A target >30%
      NT-proBNP reduction is gradually attained before discharge, and rebound NT-proBNP
      increases to levels off-target occur in up to 33% of ADHF patients who initially
      attained target early during admission.

PMID- 26216494
TI  - Analysis on therapeutic outcomes and prognostic factors of intracranial
      ependymoma: a report of 49 clinical cases in a single center.
AB  - Although intracranial ependymoma is relatively rare, it is often associated with
      great clinical aggressiveness and poor overall survival. There are controversies
      over factors affecting the prognosis of the disease. The aim of this
      retrospective study was to evaluate factors that may affect the therapeutic
      outcome and prognosis of intracranial ependymoma by reviewing the medical records
      of 49 patients who were surgically treated in our hospital between 2001 and 2014.
      Univariate and multivariate analyses were performed to identify prognostic
      variables relative to patient and tumor characteristics, and treatment
      modalities. All 49 patients (24 men and 25 women; mean age 27.6 years) underwent
      surgical resection, of whom 14 patients also underwent postoperative
      radiotherapy. Local recurrence was found in 15 (48.8 %) patients, and 22 (51.2 %)
      patients died during the follow-up periods. The 5-year recurrence rate was 65 %
      and the survival rate was 51 %. The results of statistical analysis suggested
      that preoperative extraventricular drainage and surgical resection extent were
      prognostic factors related to progression-free survival, and that age, surgical
      resection extent and histological grade were closely associated with survival.
      Interestingly, there was a significant correlation between the symptom of
      hydrocephalus and age (P = 0.010), and patients with a better clinical status
      (KPS >= 80) were significantly associated with a lower WHO grade (P = 0.007). In
      conclusion, we confirmed that surgical resection extent was the major independent
      factor affecting both recurrence and survival of patients with intracranial
      ependymoma, while age and WHO grade were prognostic factors affecting survival
      but not recurrence.

PMID- 26216496
TI  - The two last overviews by Colin Allen Wraight (1945-2014) on energy conversion in
      photosynthetic bacteria.
AB  - Colin Allen Wraight (1945-2014) was a well-known biophysicist and biochemist of
      our times-formerly Professor of Biochemistry, Biophysics and Plant Biology, and
      Head of the Department of Biochemistry, University of Illinois at Urbana
      Champaign, Urbana, IL, USA. (See a detailed Tribute to him by Govindjee et al.,
      Photosynth Res, 2015.) During the latter part of his life, Colin had (1) given an
      excellent lecture in 2008 on the overall topic of the molecular mechanisms in
      biological energy conversion, focusing on how an ubiquinone is reduced to
      ubiquinol at the so-called "two electron gate", and (2) presented a review poster
      on the design features of long distance proton transport in biological systems,
      with focus on photosynthetic bacteria (a pdf file of the original is available
      from one of us, Govindjee). We present here for historical purpose, a complete
      transcript of his 2008 lecture and his 2013 poster, which have been annotated and
      expanded by the authors of this paper. The major theme is: electron and proton
      transfer in biological systems, with emphasis on bacterial reaction centers. The
      figures, some of which were prepared by us, are presented in sequence for both
      the lecture and the poster. A common bibliography is provided at the end of the
      paper, which is divided into two parts: (I) The Lecture; and (II) The Poster. 

PMID- 26216498
TI  - The potential harms of over screening.

PMID- 26216497
TI  - Supramolecular organization of photosynthetic complexes in membranes of
      Roseiflexus castenholzii.
AB  - The photosynthetic membranes of the filamentous anoxygenic phototroph Roseiflexus
      castenholzii have been studied with electron microscopy, atomic force microscopy,
      and biochemistry. Electron microscopy of the light-harvesting reaction center
      complex produced a 3D model that aligns with the solved crystal structure of the
      RC-LH1 from Thermochromatium tepidum with the H subunit removed. Atomic force
      microscopy of the whole membranes yielded a picture of the supramolecular
      organization of the major proteins in the photosynthetic electron transport
      chain. The results point to a loosely packed membrane without accessory antenna
      proteins or higher order structure. 

PMID- 26216499
TI  - New Paradigm for the Treatment of Glucose Transporter 1 Deficiency Syndrome: Low
      Glycemic Index Diet and Modified High Amylopectin Cornstarch.
AB  - OBJECTIVE: Glucose transporter 1 deficiency syndrome is an autosomal, dominantly
      inherited neurometabolic disorder caused by mutations in the SLC2A1 gene.
      Decreased glucose transport into the brain results in seizures and cognitive
      dysfunction. The ketogenic diet is the treatment of choice, but complicated with
      compliance problems. Stabilization of blood glucose levels by low glycemic index
      diet and modified high amylopectin cornstarch would provide steady-state glucose
      transport into the brain to prevent seizures and cognitive dysfunction in
      patients with glucose transporter 1 deficiency syndrome as an alternative
      treatment. PATIENT: We report a new glucose transporter 1 deficiency syndrome
      patient (c.988C>T; p. Arg330X in the SLC2A1) treated with modified high
      amylopectin cornstarch (Glycosade) and low glycemic index diet because of
      compliance problems with the ketogenic diet. She was diagnosed at 11.5 years of
      age and was treated with the ketogenic diet between ages 12 and 18 years.
      RESULTS: She was started on modified high amylopectin cornstarch at bedtime and
      low glycemic index diet with meals and snacks every 3-4 hours. Within the first 6
      months of therapy, she improved in her seizures and cognitive functions, but
      experienced compliance problems afterwards. Neuropsychological assessment was
      stable at 12 months of therapy. CONCLUSION: This diet was easy to apply compared
      with the ketogenic diet and resulted in stable neuropsychological functioning of
      this glucose transporter 1 deficiency syndrome patient. Modified high amylopectin
      cornstarch and low glycemic index diet might be an alternative treatment in
      glucose transporter 1 deficiency syndrome patients with compliance problems to
      the ketogenic diet treatment, but additional patients should be treated to prove
      usefulness of this new treatment.

PMID- 26216501
TI  - Fatal Mycotic Cerebral Abscess in an Immunocompetent Healthy Adolescent.

PMID- 26216500
TI  - Randomized, Single-Blind, Parallel Clinical Trial on Efficacy of Oral
      Prednisolone Versus Intramuscular Corticotropin on Immediate and Continued Spasm
      Control in West Syndrome.
AB  - OBJECTIVE: A single-center, single-blind, parallel-group, randomized clinical
      trial was performed to test the null hypothesis that adrenocorticotropic hormone
      is not superior to high-dose prednisolone for treatment of newly diagnosed West
      syndrome. METHODS: Newly diagnosed infants with West syndrome were randomized to
      receive 14 days of oral prednisolone (40-60 mg/day) or a synthetically prepared
      intramuscular long-acting adrenocorticotropic hormone (40-60 IU/every other day
      [0.5-0.75 mg]) according to the United Kingdom Infantile Spasm Study protocol.
      They were blindly evaluated for infantile spasm remission by day 14,
      electroclinical remission (spasm cessation + resolution of hypsarrhythmia on a 30
      minute electroencephalograph) by day 14 and continued spasm freedom for 28 days.
      RESULTS: Ninety-seven patients were enrolled in the study, with 48 of them
      receiving prednisolone and 49 receiving ACTH. There was no significant difference
      in the baseline characteristics or risk factors for the two treatment groups. By
      day 14, cessation of infantile spasms occurred in 28/48 (58.3%) infants on
      prednisolone compared with only 18/49 (36.7%) infants given adrenocorticotropic
      hormone (P = 0.03) and electroclinical remission in 21 on prednisolone compared
      with nine on adrenocorticotropic hormone (P = 0.007). Sustained spasm control for
      28 consecutive days following electroclinical remission occurred in 15 children
      on prednisolone compared with six on adrenocorticotropic hormone (P = 0.008). The
      total number of days required for spasm cessation was significantly less in those
      treated with prednisolone (3.85 days +/- 2.4) compared with adrenocorticotropic
      hormone (8.65 days +/- 3.7) (P = 0.001). Among patients who did not achieve
      remission, there was a non-significant trend toward greater quantitative
      reduction of spasms with prednisolone than with adrenocorticotropic hormone (P =
      0.079). CONCLUSION: Synthetic adrenocorticotropic hormone of 40-60 IU/every other
      day did not yield superior rates of electroencephalographic or clinical remission
      when compared with prednisolone of 40-60 mg/day. Significantly, more patients
      achieved electroclinical remission when treated with prednisolone than with
      adrenocorticotropic hormone.

PMID- 26216502
TI  - Aberrant Executive and Frontoparietal Functional Connectivity in Very Preterm
      Infants With Diffuse White Matter Abnormalities.
AB  - BACKGROUND: Diffuse white matter abnormalities are identified in up to 80% of
      very preterm infants on magnetic resonance imaging at 40 weeks' postmenstrual
      age. Several studies have observed an association between diffuse white matter
      abnormalities and cognitive deficits. We hypothesized that very preterm infants
      (gestational age <=32 weeks) with diffuse white matter abnormalities will exhibit
      reduced executive control and frontoparietal functional connectivity compared
      with infants without diffuse white matter abnormalities measured using resting
      state functional magnetic resonance imaging at term-equivalent age. METHODS: We
      quantified diffuse white matter abnormality volume objectively using an automated
      segmentation approach and defined diffuse white matter abnormality severity as no
      mild (volume <=50th percentile; N = 13) and moderate-severe (N = 14). Resting
      state networks of interests were identified using probabilistic independent
      component analysis. Within network functional connectivity was calculated between
      the different pair of nodes in a given network using partial correlation
      coefficients. RESULTS: We studied 27 very preterm infants born at a mean
      (standard deviation) gestational age of 26.9 (2.0) weeks and imaged at 39.6 (1.4)
      weeks' postmenstrual age. Within-network connectivity was significantly reduced
      in the moderate-severe diffuse white matter abnormalities group than in the no
      mild diffuse white matter abnormalities group for the executive control (P <
      0.001) and frontoparietal (P = 0.02) networks. As expected, connectivity in three
      control resting state networks was similar: visual (P = 0.17), motor (P = 0.89),
      and somatosensory (P = 0.69) networks. CONCLUSIONS: Very preterm infants with
      moderate or severe diffuse white matter abnormalities exhibited reduced
      functional connectivity in important cognitive and attention networks. This
      aberrant connectivity may be the early life antecedent to the cognitive deficits
      reported at 2 years of age or later in such infants.

PMID- 26216504
TI  - Bioleached sludge composting drastically reducing ammonia volatilization as well
      as decreasing bulking agent dosage and improving compost quality: A case study.
AB  - Sludge bioleaching technology with Acidithiobacillus species has been
      commercially adopted for improving advanced dewatering of sludge in China since
      2010. However, up to now, little information on bioleached dewatered sludge (BS)
      composting is available. Here, we report the changes of physicochemical and
      biological properties in BS composting and evaluate compost product quality
      compared to conventional dewatered sludge (CS) composting in an engineering scale
      composting facility. The results showed that the amount of bulking agents
      required in BS composting was only about 10% of CS composting to obtain optimum
      moisture content, reducing about 700 kg bulking agents per ton fresh sludge. pH
      of BS composting mixture was slightly lower consistently by about 0.2-0.3 pH
      units than that in CS mixture in the first 30 days. Organic matter biodegradation
      in BS system mainly occurred in the first 9 days of composting. In spite of
      higher content of NH4(+)-N was found in BS mixture in related to CS mixture;
      unexpectedly the cumulative ammonia volatilization in the former was only 51% of
      the latter, indicating that BS composting drastically reduced nitrogen loss.
      Compared to CS composting system, the relative lower pH, the higher intensity of
      microbial assimilation, and the presence of water soluble Fe in BS system might
      jointly reduce ammonia volatilization. Consequently, BS compost product exhibited
      higher fertilizer values (N+P2O5+K2O=8.38%) as well as lower heavy metal levels
      due to the solubilization of sludge-borne heavy metals during bioleaching
      process. Therefore, composting of BS possesses more advantages over the CS
      composting process.

PMID- 26216503
TI  - Stability and maturity of biowaste composts derived by small municipalities:
      Correlation among physical, chemical and biological indices.
AB  - Stability and maturity are important criteria to guarantee the quality of a
      compost that is applied to agriculture or used as amendment in degraded soils.
      Although different techniques exist to evaluate stability and maturity, the
      application of laboratory tests in municipalities in developing countries can be
      limited due to cost and application complexities. In the composting facilities of
      such places, some classical low cost on-site tests to monitor the composting
      process are usually implemented; however, such tests do not necessarily clearly
      identify conditions of stability and maturity. In this article, we have applied
      and compared results of stability and maturity tests that can be easily employed
      on site (i.e. temperature, pH, moisture, electrical conductivity [EC], odor and
      color), and of tests that require more complex laboratory techniques (volatile
      solids, C/N ratio, self-heating, respirometric index, germination index [GI]).
      The evaluation of the above was performed in the field scale using 2 piles of
      biowaste applied compost. The monitoring period was from day 70 to day 190 of the
      process. Results showed that the low-cost tests traditionally employed to monitor
      the composting process on-site, such as temperature, color and moisture, do not
      provide consistent determinations with the more complex laboratory tests used to
      assess stability (e.g. respiration index, self-heating, volatile solids). In the
      case of maturity tests (GI, pH, EC), both the on-site tests (pH, EC) and the
      laboratory test (GI) provided consistent results. Although, stability was
      indicated for most of the samples, the maturity tests indicated that products
      were consistently immature. Thus, a stable product is not necessarily mature.
      Conclusively, the decision on the quality of the compost in the installations
      located in developing countries requires the simultaneous use of a combination of
      tests that are performed both in the laboratory and on-site. 

PMID- 26216505
TI  - Experimental Detection of the Intrinsic Difference in Raman Optical Activity of a
      Photoreceptor Protein under Preresonance and Resonance Conditions.
AB  - Raman optical activity (ROA) is an advanced technique capable of detecting
      structural deformations of light-absorbing molecules embedded in chromophoric
      proteins. Resonance Raman (RR) spectroscopy is widely used to enhance the band
      intensities. However, theoretical work has predicted that under resonance
      conditions the ROA spectrum resembles the shape of the RR spectrum. Herein, we
      use photoactive yellow protein (PYP) to measure the first experimental data on
      the effect of changing the excitation wavelength on the ROA spectra of a protein.
      We observe a close similarity between the shape of the RR spectrum and the
      resonance ROA spectrum of PYP. Furthermore, we experimentally verify the
      theoretical prediction concerning the ratio of the amplitudes of the ROA and
      Raman spectra. Our data demonstrate that selecting an appropriate excitation
      wavelength is a key factor for extracting structural information on a protein
      active site using ROA spectroscopy. 

PMID- 26216506
TI  - Chemotherapy in Prostate Cancer.
AB  - For approximately a decade, chemotherapy has been shown to prolong life in
      patients with metastatic castration-resistant prostate cancer (mCRPC). Since that
      time, however, only two agents have proven to prolong life (docetaxel and
      cabazitaxel). However, in the last year, the addition of chemotherapy to primary
      hormonal therapy became a standard of care for high-volume castration-sensitive
      metastatic disease. Here I will review current prostate cancer chemotherapies,
      mechanisms of resistance to those therapies, and ongoing clinical studies of
      chemotherapy combinations and novel chemotherapeutics. 

PMID- 26216507
TI  - [MicroRNAs in kidney fibrosis].
AB  - Renal fibrosis represents the final stage of most chronic kidney diseases and
      contributes to the progressive and irreversible decline in kidney function with
      accumulation of extracellular matrix components in the renal parenchyma. The
      molecular mechanisms governing the renal fibrosis process are complex and remain
      poorly understood. Recently, the profibrotic role of several microRNAs (miRNAs)
      has been described in kidney fibrosis. MiRNAs are a new class of, small non
      coding RNAs of about 20 nucleotides that act as gene expression negative
      regulators at the post-transcriptional level. Seminal studies have highlighted
      the potential importance of miRNA as new therapeutic targets and innovative
      diagnostic and/or prognostic biomarkers. This review summarizes recent scientific
      advances on the role played by miRNAs in kidney fibrogenesis and discusses
      potential clinical applications as well as future research directions. 

PMID- 26216508
TI  - Injectable PLGA microspheres encapsulating WKYMVM peptide for neovascularization.
AB  - Formyl peptide receptor-2 (FPR-2) is expressed in various cell types, such as
      phagocytes, fibroblasts, and endothelial cells. FPR-2 has been reported to play a
      significant role in inflammation and angiogenic response, and synthetic WKYMVm
      peptide has been identified as a novel peptide agonist for the FPR-2. In this
      study, we demonstrate that WKYMVm peptides stimulate the angiogenic potential of
      outgrowth endothelial cells (OECs). Upon WKYMVm peptide exposure, migration and
      proliferation of OECs were stimulated. WKYMVm effectively stimulated angiogenesis
      in tube formation assay and aortic ring assay. Furthermore, we fabricated
      injectable poly (lactide-co-glycolide) (PLGA) microspheres encapsulating WKYMVm
      peptides, which showed sustained release of cargo molecule. When WKYMVm peptide
      encapsulated microspheres were injected into the hind limb ischemia model, a
      single injection of microspheres was as effective as multiple injections of
      WKYMVm peptide in restoring blood flow from ischemic injury and promoting
      capillary growth. These results demonstrate that sustained release of WKYMVm
      peptide from microspheres in the application to ischemic hind limb extended
      angiogenic stimulation. STATEMENT OF SIGNIFICANCE: Formyl peptide receptor (FPR)
      has been reported to play an important role in inflammation and angiogenic
      response. A synthetic WKYMVm peptide has been identified as a novel peptide
      activating the FPR-2 that is expressed in a various cell types, such as
      phagocytes, fibroblasts, and endothelial cells. In this manuscript we explored a
      unique property of high-affinity ligand for formyl peptide receptors-2 (FPR-2)
      (i.e., WKYMVm). WKYMVm-induced activation of FPR2 has been reported to be crucial
      in host defense and inflammation by activation of phagocytes, monocytes, and
      lymphocytes. In this study, highlight the efficacy of WKYMVm peptide's role in
      inducing neovascularization in vivo hind limb ischemia model when the peptide was
      released from injected PLGA microspheres in sustained manner. Our results
      demonstrate that sustained release of WKYMVm peptide from microspheres have
      extended angiogenic stimulation capacity.

PMID- 26216509
TI  - Perceptions of reporting practices and barriers to reporting incidents among
      registered nurses and physicians in accredited and nonaccredited Jordanian
      hospitals.
AB  - AIMS AND OBJECTIVES: To explore the awareness of the incident reporting system,
      incident reporting practices and barriers to reporting incidents among Jordanian
      staff nurses and physicians in accredited and nonaccredited hospitals.
      BACKGROUND: Reporting medical incidents is an important element of patient safety
      enhancement and quality of care improvement and it should be an integral part of
      the organisational culture. DESIGN: A descriptive exploratory survey was used for
      the present study. METHODS: A modified version of the Incident Reporting
      Questionnaire was used to collect data from 307 nurses and 144 physicians at
      seven hospitals (four accredited and three not accredited) in Jordan. The
      response rate was 28.8% for nurses and 58.8% for physicians. RESULTS: Nurses were
      more aware of the incident reporting system than physicians. Physicians were less
      likely to report any incident on 50% or more of occasions. The major three
      barriers to reporting incidents were believing that there was no point in
      reporting near misses, lack of feedback and fear of disciplinary actions.
      CONCLUSION: The study showed significant differences between nurses in accredited
      and nonaccredited hospitals regarding barriers to reporting incidents and
      reporting practices. RELEVANCE TO CLINICAL PRACTICE: Nurse administrators should
      modify existing systems for reporting incidents to overcome the barriers as shown
      in the present study.

PMID- 26216510
TI  - Proximal tubular efflux transporters involved in renal excretion of p-cresyl
      sulfate and p-cresyl glucuronide: Implications for chronic kidney disease
      pathophysiology.
AB  - The uremic solutes p-cresyl sulfate (pCS) and p-cresyl glucuronide (pCG)
      accumulate in patients with chronic kidney disease (CKD), and might contribute to
      disease progression. Moreover, retention of these solutes may directly be related
      to renal tubular function. Here, we investigated the role of the efflux
      transporters Multidrug Resistance Protein 4 (MRP4) and Breast Cancer Resistance
      Protein (BCRP) in pCS and pCG excretion, and studied the impact of both solutes
      on the phenotype of human conditionally immortalized renal proximal tubule
      epithelial cells (ciPTEC). Our results show that p-cresol metabolites accumulate
      during CKD, with a shift from sulfation to glucuronidation upon progression.
      Moreover, pCS inhibited the activity of MRP4 by 40% and BCRP by 25%, whereas pCG
      only reduced MRP4 activity by 75%. Moreover, BCRP-mediated transport of both
      solutes was demonstrated. Exposure of ciPTEC to pCG caused epithelial-to
      mesenchymal transition, indicated by increased expression of vimentin and Bcl-2,
      and diminished E-cadherin. This was associated with altered expression of key
      tubular transporters. In conclusion, BCRP is likely involved in the renal
      excretion of both solutes, and pCG promotes phenotypical changes in ciPTEC,
      supporting the notion that uremic toxins may be involved in CKD progression by
      negatively affecting renal tubule cell phenotype and functionality. 

PMID- 26216511
TI  - Structural diversity of late transition metal complexes with flexible tetra-NHC
      ligands.
AB  - The synthesis of copper, gold, nickel, palladium, platinum, and iron complexes
      with open chain tetra-N-heterocyclic carbene (NHC) ligands via transmetalation
      using silver NHC complexes is presented. The obtained complexes show differing
      coordination geometries depending on both ligand structure and metal. While the
      complexes of the coinage metals form di- or tetranuclear structures, the group 10
      metal complexes exhibit a distorted square planar coordination geometry at the
      metal centers. In the case of iron an enhanced flexibility of the ligand - caused
      by a longer alkyl bridge - leads to octahedral complexes with a sawhorse-type
      coordination by the tetracarbene ligand and two cis acetonitrile ligands. To the
      best of our knowledge, this is the first known example of a tetracarbene ligand
      in sawhorse-type coordination within an octahedral coordination sphere. The
      remaining cis-labile sites are prone to exchange reactions as shown by addition
      of trimethylphosphine. 

PMID- 26216512
TI  - The antithrombotic effect of RSNK in blood-stasis model rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Reduction of Sheng-Nao-Kang decoction (RSNK),
      composed of Salvia miltiorrhiza Bge., Ligusticum chuanxiong Hort., Astragalus
      membranaceus (Fisch.) Bunge., Pueraria lobata (Willd.) Ohwi., Paeonia lactiflora
      Pall. and Panax notoginseng (Burk.) F. H. Chen., is a modified traditional
      Chinese medicinal formula of Sheng-Nao-Kang pill preparation, which has been
      investigated its protective effect on focal cerebral ischemia-reperfusion injury
      in rat in our previous report. AIM OF THE STUDY: To evaluate the antithrombotic
      effect of RSNK in blood stasis model rats and explore the potential mechanisms.
      MATERIALS AND METHODS: Subcutaneous injection of norepinephrine and bovine serum
      albumin combined with ice water bath was used to establish the acute blood stasis
      rat model. The anticoagulant activities were investigated by measuring activated
      partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT),
      and the content of fibrinogen (FIB). Meanwhile, the levels of thromboxane A2
      (TXA2), prostaglandins I2 (PGI2), endothelial nitric oxide synthase (eNOS) and
      endothelin (ET) were detected. RESULTS: The treatment of RSNK was able to prolong
      APTT, TT and PT, and decrease FIB content obviously. Furthermore, it markedly
      suppressed TXB2 level and up-regulated 6-keto-PGF1alpha level of the blood-stasis
      model rats, accompanied with the decrease of T/K. The level of ET and TXA2 in
      plasma was down-regulated and the levels of eNOS in plasma and PGI2 in serum was
      up-regulated in RSNK-treated rats compared with model rats (P<0.05). CONCLUSION:
      The present study suggested that RSNK possessed remarkable antithrombotic
      property in blood stasis model rats induced by ice water bath and subcutaneous
      injection of norepinephrine and bovine serum albumin. This property could be
      associated with its anticoagulation activity, the regulation of active substances
      in vascular endothelium and maintaining the balance of TXA2 and PGI2.

PMID- 26216513
TI  - An ethnobotanical study of anti-malarial plants among indigenous people on the
      upper Negro River in the Brazilian Amazon.
AB  - BACKGROUND: In this article we present the plants used for the treatment of
      malaria and associated symptoms in Santa Isabel do Rio Negro in the Brazilian
      Amazon. The region has important biological and cultural diversities including
      more than twenty indigenous ethnic groups and a strong history in traditional
      medicine. OBJECTIVE: The aims of this study are to survey information in the
      Baniwa, Bare, Desana, Piratapuia, Tariana, Tukano, Tuyuca and Yanomami ethnic
      communities and among caboclos (mixed-ethnicity) on (a) plant species used for
      the treatment of malaria and associated symptoms, (b) dosage forms and (c)
      distribution of these anti-malarial plants in the Amazon. METHODS: Information
      was obtained through classical ethnobotanical and ethnopharmacological methods
      from interviews with 146 informants in Santa Isabel municipality on the upper
      Negro River, Brazil. RESULTS: Fifty-five mainly native neotropical plant species
      from 34 families were in use. The detailed uses of these plants were documented.
      The result was 187 records (64.5%) of plants for the specific treatment of
      malaria, 51 records (17.6%) of plants used in the treatment of liver problems and
      29 records (10.0%) of plants used in the control of fevers associated with
      malaria. Other uses described were blood fortification ('dar sangue'), headache
      and prophylaxis. Most of the therapeutic preparations were decoctions and
      infusions based on stem bark, root bark and leaves. These were administered by
      mouth. In some cases, remedies were prepared with up to three different plant
      species. Also, plants were used together with other ingredients such as insects,
      mammals, gunpowder and milk. CONCLUSION: This is the first study on the anti
      malarial plants from this region of the Amazon. Aspidosperma spp. and
      Ampelozizyphus amazonicus Ducke were the most cited species in the communities
      surveyed. These species have experimental proof supporting their anti-malarial
      efficacy. The dosage of the therapeutic preparations depends on the kind of
      plant, quantity of plant material available, the patient's age (children and
      adults) and the local expert. The treatment time varies from a single dose to up
      to several weeks. Most anti-malarial plants are domesticated or grow
      spontaneously. They are grown in home gardens, open areas near the communities,
      clearings and secondary forests, and wild species grow in areas of seasonally
      flooded wetlands and terra firme ('solid ground') forest, in some cases in
      locations that are hard to access. Traditional knowledge of plants was found to
      be falling into disuse presumably as a consequence of the local official health
      services that treat malaria in the communities using commercial drugs. Despite
      this, some species are used in the prevention of this disease and also in the
      recovery after using conventional anti-malarial drugs.

PMID- 26216514
TI  - Hippocampal-thalamic wiring in medial temporal lobe epilepsy: Enhanced
      connectivity per hippocampal voxel.
AB  - OBJECTIVE: Medial temporal lobe epilepsy (TLE) with hippocampal sclerosis is
      often accompanied by widespread changes in ipsilateral and contralateral white
      matter connectivity. Recent studies have proposed that patients may show
      pathologically enhanced wiring of the limbic circuits. To better address this
      issue, we specifically probed connection patterns between hippocampus and
      thalamus and examined their impact on cognitive function. METHODS: A group of 44
      patients with TLE (22 with right and 22 with left hippocampal sclerosis) and 24
      healthy control participants were examined with high-resolution T1 imaging,
      memory functional magnetic resonance imaging (fMRI) and probabilistic diffusion
      tractography. Thirty-four patients had further extensive neuropsychological
      testing. After whole brain segmentation with FreeSurfer, tractography streamline
      samples were drawn with hippocampus as the seed and thalamus as the target
      region. Two tractography strategies were applied: The first targeted the anatomic
      thalamic volume segmented in FreeSurfer and the second a functional region of
      interest in the mediodorsal thalamus derived from the activation during delayed
      recognition memory. RESULTS: We found a pronounced enhancement of connectivity
      between the sclerotic hippocampus and the ipsilateral thalamus both in the right
      and left TLE as compared to healthy control participants. This finding held for
      both the anatomically and the functionally defined thalamic target. Although
      differences were apparent in the number of absolute fibers, they were most
      pronounced when correcting for hippocampal volume. In terms of cognitive
      function, the number of hippocampal-thalamic connections was negatively
      correlated with performance in a variety of executive tasks, notably in the Trail
      Making Test, thus suggesting that the pathologic wiring did not compensate
      cognitive curtailing. SIGNIFICANCE: We suggest that TLE is accompanied by an
      abnormal and dysfunctional enhancement of connectivity between the hippocampus
      and the thalamus, which is maximal on the side of the sclerosis. This pathologic
      pattern of limbic wiring might reflect structural remodeling along common
      pathways of seizure propagation.

PMID- 26216515
TI  - Suppression of IL-7-dependent Effector T-cell Expansion by Multipotent Adult
      Progenitor Cells and PGE2.
AB  - T-cell depletion therapy is used to prevent acute allograft rejection, treat
      autoimmunity and create space for bone marrow or hematopoietic cell
      transplantation. The evolved response to T-cell loss is a transient increase in
      IL-7 that drives compensatory homeostatic proliferation (HP) of mature T cells.
      Paradoxically, the exaggerated form of this process that occurs following
      lymphodepletion expands effector T-cells, often causing loss of immunological
      tolerance that results in rapid graft rejection, autoimmunity, and exacerbated
      graft-versus-host disease (GVHD). While standard immune suppression is unable to
      treat these pathologies, growing evidence suggests that manipulating the
      incipient process of HP increases allograft survival, prevents autoimmunity, and
      markedly reduces GVHD. Multipotent adult progenitor cells (MAPC) are a clinical
      grade immunomodulatory cell therapy known to alter gamma-chain cytokine responses
      in T-cells. Herein, we demonstrate that MAPC regulate HP of human T-cells,
      prevent the expansion of Th1, Th17, and Th22 effectors, and block the development
      of pathogenic allograft responses. This occurs via IL-1beta-primed secretion of
      PGE2 and activates T-cell intrinsic regulatory mechanisms (SOCS2, GADD45A). These
      data provide proof-of-principle that HP of human T-cells can be targeted by
      cellular and molecular therapies and lays a basis for the development of novel
      strategies to prevent immunopathology in lymphodepleted patients. 

PMID- 26216516
TI  - Intracisternal Gtf2i Gene Therapy Ameliorates Deficits in Cognition and Synaptic
      Plasticity of a Mouse Model of Williams-Beuren Syndrome.
AB  - Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a
      heterozygous deletion of 26-28 genes at chromosome band 7q11.23.
      Haploinsufficiency at GTF2I has been shown to play a major role in the
      neurobehavioral phenotype. By characterizing the neuronal architecture in four
      animal models with intragenic, partial, and complete deletions of the WBS
      critical interval (DeltaGtf2i(+/-), DeltaGtf2i( -/-), PD, and CD), we clarify the
      involvement of Gtf2i in neurocognitive features. All mutant mice showed
      hypersociability, impaired motor learning and coordination, and altered anxiety
      like behavior. Dendritic length was decreased in the CA1 of DeltaGtf2i(+/-),
      DeltaGtf2i ( -/-), and CD mice. Spine density was reduced, and spines were
      shorter in DeltaGtf2i ( -/-), PD, and CD mice. Overexpression of Pik3r1 and
      downregulation of Bdnf were observed in DeltaGtf2i(+/-), PD, and CD mice.
      Intracisternal Gtf2i-gene therapy in CD mice using adeno-associated virus
      resulted in increased mGtf2i expression and normalization of Bdnf levels, along
      with beneficial effects in motor coordination, sociability, and anxiety, despite
      no significant changes in neuronal architecture. Our findings further indicate
      that Gtf2i haploinsufficiency plays an important role in the neurodevelopmental
      and cognitive abnormalities of WBS and that it is possible to rescue part of this
      neurocognitive phenotype by restoring Gtf2i expression levels in specific brain
      areas. 

PMID- 26216518
TI  - Hypertension and Polypharmacy in Elderly Nursing Home Residents: When Less is
      More.

PMID- 26216517
TI  - Antisense MicroRNA Therapeutics in Cardiovascular Disease: Quo Vadis?
AB  - Heart failure (HF) is the end result of a diverse set of causes such as genetic
      cardiomyopathies, coronary artery disease, and hypertension and represents the
      primary cause of hospitalization in Europe. This serious clinical disorder is
      mostly associated with pathological remodeling of the myocardium, pump failure,
      and sudden death. While the survival of HF patients can be prolonged with
      conventional pharmacological therapies, the prognosis remains poor. New
      therapeutic modalities are thus needed that will target the underlying causes and
      not only the symptoms of the disease. Under chronic cardiac stress, small
      noncoding RNAs, in particular microRNAs, act as critical regulators of cardiac
      tissue remodeling and represent a new class of therapeutic targets in patients
      suffering from HF. Here, we focus on the potential use of microRNA inhibitors as
      a new treatment paradigm for HF. 

PMID- 26216519
TI  - Are calving interval, abortions, incidence of stillbirths and pre-weaning losses
      in Nguni cows associated with linear type traits?
AB  - The association of six linear type traits with calving interval, abortions,
      incidence of stillbirths and pre-weaning losses in Nguni cows in semi-arid and
      sub-humid communal areas was investigated. It was hypothesised that the odds of a
      cow having caving interval greater than 1 year, aborting, experiencing
      stillbirths or losing a calf from calving to weaning decreased with increase in
      body depth, rump height, flank circumference, chest circumference, navel height
      and body length. Navel height was measured as the distance from the ground to the
      lowest point of the cow's belly bottom (navel). Data were collected from a total
      of 200 Nguni cows from two sites experiencing sub-humid and semi-arid
      environments (100 each) between May and June 2013. Cows in sub-humid regions were
      2.57 times more likely to have a calving interval of 1 year than cows in semi
      arid areas. As body depth increased, the number of calves lost by a cow before
      weaning decreased linearly (p < 0.05) in all parities except parity 4. Cows in
      semi-arid regions were 2.13 times more likely to lose a calf from calving to
      weaning. For each unit increase in body depth, the odds of a cow aborting
      decreased by 1.12 and the odds of a cow having stillbirth decreased by 1.15. Rump
      height, flank circumference, chest circumference, navel height and body length
      were not associated with calving interval, abortions, incidence of stillbirths
      and pre-weaning losses. It was, therefore, concluded that body depth influences
      calving interval, incidence of stillbirths and abortions in Nguni cows.

PMID- 26216520
TI  - Optogenetic Activation of Adenosine A2A Receptor Signaling in the Dorsomedial
      Striatopallidal Neurons Suppresses Goal-Directed Behavior.
AB  - The striatum has an essential role in neural control of instrumental behaviors by
      reinforcement learning. Adenosine A(2A) receptors (A(2A)Rs) are highly enriched
      in the striatopallidal neurons and are implicated in instrumental behavior
      control. However, the temporal importance of the A(2A)R signaling in relation to
      the reward and specific contributions of the striatopallidal A(2A)Rs in the
      dorsolateral striatum (DLS) and the dorsomedial striatum (DMS) to the control of
      instrumental learning are not defined. Here, we addressed temporal relationship
      and sufficiency of transient activation of optoA(2A)R signaling precisely at the
      time of the reward to the control of instrumental learning, using our newly
      developed rhodopsin-A2AR chimeras (optoA(2A)R). We demonstrated that transient
      light activation of optoA(2A)R signaling in the striatopallidal neurons in 'time
      locked' manner with the reward delivery (but not random optoA(2A)R activation)
      was sufficient to change the animal's sensitivity to outcome devaluation without
      affecting the acquisition or extinction phases of instrumental learning. We
      further demonstrated that optogenetic activation of striatopallidal A(2A)R
      signaling in the DMS suppressed goal-directed behaviors, as focally genetic
      knockdown of striatopallidal A(2A)Rs in the DMS enhanced goal-directed behavior
      by the devaluation test. By contrast, optogenetic activation or focal AAV-Cre
      mediated knockdown of striatopallidal A(2A)R in the DLS had relatively limited
      effects on instrumental learning. Thus, the striatopallidal A(2A)R signaling in
      the DMS exerts inhibitory and predominant control of goal-directed behavior by
      acting precisely at the time of reward, and may represent a therapeutic target to
      reverse abnormal habit formation that is associated with compulsive obsessive
      disorder and drug addiction.

PMID- 26216522
TI  - A dual target-recycling amplification strategy for sensitive detection of
      microRNAs based on duplex-specific nuclease and catalytic hairpin assembly.
AB  - A dual target-recycling amplification strategy for sensitive detection of
      microRNAs based on duplex-specific nuclease and catalytic hairpin assembly was
      reported for the first time. 

PMID- 26216521
TI  - The Calpain Inhibitor A-705253 Attenuates Alcohol-Seeking and Relapse with Low
      Side-Effect Profile.
AB  - Preclinical studies revealed contribution of N-methyl-D-aspartate receptors
      (NMDARs) to a variety of neuropsychiatric diseases including alcoholism, but
      development of NMDAR antagonists for therapeutic use has been a challenge, in
      part due to severe side effects. One of the key intracellular events resulting
      from stimulation of NMDAR is activation of calpains-calcium-dependent cysteine
      proteases. Here we studied whether inhibition of calpains would produce
      therapeutic-like effects of NMDAR antagonists but without their NMDAR-mediated
      side-effect profile. The calpain inhibitor A-705253 (3-10 mg/kg) was tested in a
      model of cue-induced reinstatement of alcohol-seeking behavior in post-dependent
      Wistar rats and in an alcohol deprivation effect (ADE) model in long-term alcohol
      drinking Wistar rats, two behavioral models for alcohol-seeking and relapse,
      respectively. We also tested the effect of A-705253 on the saccharine deprivation
      effect (SDE) as a selectivity measure. Acute treatment with A-705253 dose
      dependently reduced cue-induced reinstatement of alcohol-seeking behavior.
      Repeated administration of A-705253 caused significant reductions of relapse-like
      excessive alcohol intake during the post-abstinence drinking days, an effect that
      persisted during two more successive drug-free drinking weeks, which was
      selective for the ADE as the SDE was unaffected. However, A-705253 did not
      produce psychostimulant, cognition impairing (delayed-matching-to-position), or
      psychotomimetic effects (specifically, phencyclidine discriminative stimulus
      effects). Taken together, these results demonstrate the involvement of calpains
      in alcohol-seeking and relapse and present a rationale for a novel
      pharmacological intervention that may reduce craving and relapse with minimal
      side effects in alcohol-dependent patients.

PMID- 26216523
TI  - The effect of ACP1, ADA6 and PTPN22 genetic polymorphisms on the association
      between p53 codon 72 polymorphism and endometriosis.
AB  - PURPOSE: Association between p53 codon 72 and endometriosis has been observed in
      populations of East Asia but not in those of European descent. Genetic
      polymorphisms could interact with p53 codon 72 influencing its association with
      endometriosis, thus explaining these differences among populations. METHODS: 130
      women hospitalized for endometriosis and a sample of 250 women without
      endometriosis have been studied. All women were from the White population of
      Rome. ACP1, PTPN22, ADA6 and p53 codon 72 genotypes were determined by DNA
      analysis. Statistical analysis was performed by SPSS package. Three-way
      contingency table analyses were performed by a log linear model according to
      Sokal and Rohlf. RESULTS: There is an epistatic interaction among ADA6, p53 codon
      72 and endometriosis resulting in a positive association between carriers of *Pro
      allele of p53 codon 72 and endometriosis in women carrying the ADA6 *1 allele.
      PTPN22 and ACP1 show an additive effect with p53 codon 72 concerning their effect
      on endometriosis. The strength of association between p53 codon 72 and
      endometriosis is positively correlated with the number of the three factors
      considered. CONCLUSION: ADA6, PTPN22 and ACP1 are involved in immune reactions:
      since endometriosis has an autoimmune component, a cooperative interaction among
      these genetic systems appears biological plausible. The present result could
      contribute to explain the differences observed among populations concerning the
      association between p53 codon 72 and endometriosis.

PMID- 26216524
TI  - The synthesis and dynamic structures of multinuclear complexes of large
      porphyrinoids expanded by phenylene and thienylene spacers.
AB  - 1,3-Bis(2-pyrryl)benzene was used to prepare dibenziamethyrin, in which two
      pyrrole units of [24]amethyrin(1.0.0.1.0.0) are replaced by benzene. 1,4-Bis(2
      pyrryl)benzene, 2,5-bis(2-pyrryl)thiophene, and 4,4'-bis(2-pyrryl)biphenyl were
      also used in place of 2,2'-bipyrrole to give expanded analogues of
      [24]rosarin(1.0.1.0.1.0) and [32]octaphyrin(1.0.1.0.1.0.1.0). These large
      porphyrinoids can incorporate multiple metal units of Rh(CO)2 and Pd(pi-allyl)
      with considerable deviation of the metal atoms from the dipyrrin planes,
      evidenced by X-ray crystallography. The coordinated Rh(CO)2 group shuttled
      between both sides of the macrocycle; the rate was dependent on the spacer, ring
      size, and number of metal atoms. Variable temperature (1) H NMR spectroscopy
      showed that the tris-rhodium complexes of the expanded rosarins with 1,4
      phenylene or 2,5-thienylene spacers adopt a C3v -symmetric form and a Cs 
      symmetric form as a result of the Rh(CO)2 groups hopping through the macrocycle
      cavity. The C3v -symmetric form has a greater dipole moment and, therefore, is
      favored in solvents of greater polarity. The Rh(CO)2 groups in the tris-rhodium
      complex of the expanded rosarin with 4,4'-biphenylene spacers hop so fast that an
      averaged spectral pattern (D3h ) was seen in the (1) H NMR spectrum, even at -60 
      degrees C. Expanded octaphyrins with 1,4-phenylene and 2,5-thienylene spacers
      bind four Rh(CO)2 groups outside the macrocycle cavity to form a D2d -symmetric
      saddle-shaped structure that did not show any dynamic behavior on the NMR
      timescale, even at 80  degrees C. This tetranuclear complex is one of the largest
      porphyrinoid metal complexes characterized by X-ray crystallography to date. 

PMID- 26216525
TI  - Longitudinal Analyses of Presenteeism and Its Role as a Predictor of Sick Leave
      in Patients With Ankylosing Spondylitis.
AB  - OBJECTIVE: To investigate, in a cohort of patients with ankylosing spondylitis
      (AS) adequately treated with infliximab, changes over time in presenteeism and
      the role of presenteeism relative to that of the Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional
      Index (BASFI) in predicting sick leave. METHODS: Data were analyzed from 71
      patients with paid work and taking a stable dose of infliximab participating in a
      96-week study with 5 assessment points. Covariates included presenteeism, sick
      leave, time, sex, age, BASDAI, BASFI, Bath Ankylosing Spondylitis Metrology
      Index, and part- or full-time work. Presenteeism represented the AS impact on
      productivity (by visual analog scale, range 0-10, where 10 = completely
      unproductive). Sick leave represented the number of days absent from work due to
      AS in the last 6 months. A linear mixed-effects model for presenteeism, and
      hurdle and zero-inflated count models for sick leave were explored. RESULTS: Mean
      +/- SD presenteeism ranged from 2.2 +/- 2.2 to 3.8 +/- 7.8, and sick leave
      occurred in 8-17% of the patients during the 6-month period. Presenteeism
      positively correlated with BASDAI and BASFI, but was not significantly influenced
      by time. The chance of incurring sick leave was affected by presenteeism but not
      by BASDAI and BASFI. Conditional on being absent from work, the effect of
      presenteeism on the length of sick leave (in days) was much stronger than BASDAI
      and BASFI. For presenteeism >=5, an increase of 1 unit in presenteeism yielded an
      increase by 36-40% (or 2-12 days) in the length of sick leave during the
      following 6 months. CONCLUSION: Presenteeism, even measured by a simple visual
      analog scale, was an important factor to explain future sick leave.

PMID- 26216526
TI  - Seagrass meadows (Posidonia oceanica) distribution and trajectories of change.
AB  - Posidonia oceanica meadows are declining at alarming rates due to climate change
      and human activities. Although P. oceanica is considered the most important and
      well-studied seagrass species of the Mediterranean Sea, to date there has been a
      limited effort to combine all the spatial information available and provide a
      complete distribution of meadows across the basin. The aim of this work is to
      provide a fine-scale assessment of (i) the current and historical known
      distribution of P. oceanica, (ii) the total area of meadows and (iii) the
      magnitude of regressive phenomena in the last decades. The outcomes showed the
      current spatial distribution of P. oceanica, covering a known area of 1,224,707
      ha, and highlighted the lack of relevant data in part of the basin (21,471 linear
      km of coastline). The estimated regression of meadows amounted to 34% in the last
      50 years, showing that this generalised phenomenon had to be mainly ascribed to
      cumulative effects of multiple local stressors. Our results highlighted the
      importance of enforcing surveys to assess the status and prioritize areas where
      cost-effective schemes for threats reduction, capable of reversing present
      patterns of change and ensuring P. oceanica persistence at Mediterranean scale,
      could be implemented.

PMID- 26216527
TI  - Properties of cervical and ocular vestibular evoked myogenic potentials (cVEMPs
      and oVEMPs) evoked by 500 Hz and 100 Hz bone vibration at the mastoid.
AB  - OBJECTIVE: To define and compare the input-output properties of 500 Hz and 100 Hz
      bone-conducted (BC) transmastoid stimulation when evoking cVEMPs and oVEMPs. The
      findings for 500 Hz were compared with those previously reported for air
      conducted (AC) 500 Hz stimulation. METHODS: Twelve healthy subjects (18-57 years
      old) participated in this study, with simultaneous recordings of cVEMPs and
      oVEMPs bilaterally. Initial intensities of 138 dB (FL) were used and then reduced
      in 3 or 6 dB increments to 105 dB. RESULTS: For BC 500 Hz, like AC 500 Hz, the
      relationship between the stimulus and reflex output fitted a power law for most
      peaks, but not the initial peak of the oVEMP. Some of the subjects did not have
      early crossed oVEMP responses for BC 500 Hz but all did for 100 Hz. For BC 100
      Hz, while the initial waveforms were similar, many of the peaks showed a tendency
      to saturate at the higher intensities. For both BC 500 Hz and 100 Hz, the initial
      (contralateral) oVEMP peaks had a higher threshold than for the (ipsilateral)
      cVEMP responses although this difference was more marked for 500 Hz. CONCLUSIONS:
      BC 500 Hz shows similar properties to AC 500 Hz, consistent with an overlapping
      spectrum of afferents being excited by both, with bilateral effects for the BC
      stimulus. BC 100 Hz evokes more non-vestibular peaks, presumably from muscle
      afferents, for the SCM recordings but is a more reliable method of evoking the
      early crossed potentials of the oVEMP. SIGNIFICANCE: BC 500 Hz is a useful
      adjunct to the AC 500 Hz stimulus and has similar properties. The BC 100 Hz
      stimulus may be a more reliable method of evoking the early crossed oVEMP
      responses.

PMID- 26216528
TI  - A Pharmacometabonomic Approach To Predicting Metabolic Phenotypes and
      Pharmacokinetic Parameters of Atorvastatin in Healthy Volunteers.
AB  - Genetic polymorphism and environment each influence individual variability in
      drug metabolism and disposition. It is preferable to predict such variability,
      which may affect drug efficacy and toxicity, before drug administration. We
      examined individual differences in the pharmacokinetics of atorvastatin by
      applying gas chromatography-mass spectrometry-based metabolic profiling to
      predose plasma samples from 48 healthy volunteers. We determined the level of
      atorvastatin in plasma using liquid chromatography-tandem mass spectrometry. With
      the endogenous molecules, which showed a good correlation with pharmacokinetic
      parameters, a refined partial least-squares model was calculated based on predose
      data from a training set of 36 individuals and exhibited good predictive
      capability for the other 12 individuals in the prediction set. In addition, the
      model was successfully used to predictively classify individual pharmacokinetic
      responses into subgroups. Metabolites such as tryptophan, alanine, arachidonic
      acid, 2-hydroxybutyric acid, cholesterol, and isoleucine were indicated as
      candidate markers for predicting by showing better predictive capability for
      explaining individual differences than a conventional physiological index. These
      results suggest that a pharmacometabonomic approach offers the potential to
      predict individual differences in pharmacokinetics and therefore to facilitate
      individualized drug therapy. 

PMID- 26216529
TI  - Peri-prosthetic fractures around tumor endoprostheses: a retrospective analysis
      of eighteen cases.
AB  - PURPOSE: Tumour hip and knee endoprostheses have become the mainstay for
      reconstruction of patients with bone tumours. Fixation into host bone has
      improved over time. However, some patients present with a peri-prosthetic
      fracture over follow-up. The objective of this study was to analyse the mode of
      presentation and survival of implant after a peri-prosthetic fracture around a
      tumour endoprosthesis. METHODS: Eighteen peri-prosthetic fractures (17 patients)
      were included. All patients were treated at a tertiary care center. There were 11
      (65%) women; the median age at the time of fracture was 38 years old. All
      implants were cemented and all knee endoprostheses were fixed-hinge. Twelve (67%)
      fractures occurred after femoral resection and six (33%) fractures after proximal
      tibial resection. RESULTS: There were three femoral neck fractures (UCS C), three
      femoral shaft type C fractures, two femoral shaft type B1, one tibial shaft type
      B2, three tibial shaft type C, three ankle fractures (UCS C) and three patella
      fractures (UCS F). Two fractures were treated conservatively and 16 were operated
      on. Only one patient had the implant revised. There were eight (44%) failures
      over follow-up; none of the conservative treatment failed. The cumulative
      probability of failure for any reason was 27% (8-52) and 55% (22-79) at five and
      ten years, respectively. CONCLUSIONS: Peri-prosthetic fractures around massive
      endoprostheses are different from that of standard implants. There are more type
      C fractures; internal fixation is an attractive option at the time of
      presentation but the risk of revision over follow-up is high and patients should
      be informed accordingly.

PMID- 26216531
TI  - Management of periprosthetic acetabular fractures in elderly patients--a
      minimally invasive approach.
AB  - PURPOSE: Periprosthetic acetabular fractures are rare and in the current
      literature largely underreported. The management is reported to be difficult.
      Treatment varies from non-operative to open reduction and internal fixation up to
      revision of the acetabular components. METHODS: A prospective consecutive case
      series in acetabular fractures was performed in a level 1 trauma centre. All
      patients with pre-existing total hip replacement were followed up for one year.
      Perioperative data, complications, radiological results, functional outcome and
      quality of life were measured. RESULTS: Eight (15%) of 53 patients who were
      included in the study underwent total hip arthroplasty before and had stable
      implants at time of fracture. Mean age of the patients was 83 years. All of them
      were female. Mean operative time was 85 minutes. There were no soft tissue
      complications like infection or nerve damage in the post-operative course. No
      revision was needed. Two patients died in between the follow up. The Harris hip
      score was a mean of 77, with quality of life comparable to persons in the same
      age. CONCLUSIONS: Minimally invasive reconstruction of the anterior column is a
      viable method to conserve stable acetabular components in this type of fracture.
      Short operation time and limited incisions are the most conclusive advantages.

PMID- 26216530
TI  - Surgical treatment for young adult hip dysplasia: joint-preserving options.
AB  - Developmental dysplasia of the hip (DDH) is a spectrum of disorders that results
      in anatomic abnormalities leading to increased contact stress in the joint and,
      eventually, secondary osteoarthritis. However, many patients with DDH become
      symptomatic before the severe degenerative changes of the hip because of abnormal
      hip biomechanics, mild hip instability, impingement, or associated intra
      articular pathology. Early diagnosis and appropriate treatment for DDH are of the
      utmost importance. With the modification of techniques like pelvic osteotomy and
      capsular arthroplasty, and the introduction of intracapsular procedures such as
      arthroscopy and femoral head-neck junction osteochondroplasty, many young
      patients with symptomatic hip dysplasia may benefit from joint preservation
      procedures. We review the current development of these concepts and the
      associated surgical techniques.

PMID- 26216532
TI  - PH-sauvagine from the skin secretion of Phyllomedusa hypochondrialis: A novel CRF
      like peptide with smooth muscle contraction activity.
AB  - Amphibian skin, and particularly that of south/Central American phyllomedusine
      frogs, is supposed to be "a huge factory and store house of a variety of active
      peptides". The 40 amino acid amphibian CRF-like peptide, sauvagine, is a
      prototype member of a unique family of these Phyllomedusa skin peptides. In this
      study, we describe for the first time the structure of a mature novel peptide
      from the skin secretion of the South American orange-legged leaf frog,
      Phyllomedusa hypochondrialis, which belongs to the amphibian CRF/sauvagine
      family. Partial amino acid sequence from the N-terminal was obtained by automated
      Edman degradation with the following structure: pGlu-GPPISIDLNMELLRNMIEI-. The
      biosynthetic precursor of this novel sauvagine peptide, consisted of 85 amino
      acid residues and was deduced from cDNA library constructed from the same skin
      secretion. Compared with the standard sauvagine from the frog, Phyllomedusa
      sauvagei, this novel peptide was found to exert similar contraction effects on
      isolated guinea-pig colon and rat urinary bladder smooth muscle preparations.

PMID- 26216533
TI  - Early inhibition of hepatocyte innate responses by hepatitis B virus.
AB  - BACKGROUND & AIMS: The outcome of hepatitis B virus (HBV) infection may be
      influenced by early interactions between the virus and hepatocyte innate immune
      responses. To date, the study of such interactions during the very early step of
      infection has not been adequately investigated. METHODS: We used the HepaRG cell
      line, as well as primary human hepatocytes to analyze, within 24h of exposure to
      HBV, either delivered by a physiologic route or baculovirus vector (Bac-HBV), the
      early modulation of the expression of selected antiviral/pro-inflammatory
      cytokines and interferon stimulated genes. Experiments were also performed in the
      presence or absence of innate receptor agonists to investigate early HBV-induced
      blockade of innate responses. RESULTS: We show that hepatocytes themselves could
      detect HBV, and express innate genes when exposed to either HBV virions or Bac
      HBV. Whereas Bac-HBV triggered a strong antiviral cytokine secretion followed by
      the clearance of replicative intermediates, a physiologic HBV exposure led to an
      abortive response. The early inhibition of innate response by HBV was mainly
      evidenced on Toll-like receptor 3 and RIG-I/MDA5 signaling pathways upon
      engagement with exogenous agonist, leading to a decreased expression of several
      pro-inflammatory and antiviral cytokine genes. Finally, we demonstrate that this
      early inhibition of dsRNA-mediated response is due to factor(s) present in the
      HBV inoculum, but not being HBsAg or HBeAg themselves, and does not require de
      novo viral protein synthesis and replication. CONCLUSIONS: Our data provide
      strong evidence that HBV viral particles themselves can readily inhibit host
      innate immune responses upon virion/cell interactions, and may explain, at least
      partially, the "stealthy" character of HBV.

PMID- 26216534
TI  - Transcriptional coordination of physiological responses in Nannochloropsis
      oceanica CCMP1779 under light/dark cycles.
AB  - Nannochloropsis oceanica CCMP1779 is a marine unicellular stramenopile and an
      emerging reference species for basic research on oleogenic microalgae with
      biotechnological relevance. We investigated its physiology and transcriptome
      under light/dark cycles. We observed oscillations in lipid content and a
      predominance of cell division in the first half of the dark phase. Globally, more
      than 60% of the genes cycled in N. oceanica CCMP1779, with gene expression
      peaking at different times of the day. Interestingly, the phase of expression of
      genes involved in certain biological processes was conserved across
      photosynthetic lineages. Furthermore, in agreement with our physiological studies
      we found the processes of lipid metabolism and cell division enriched in cycling
      genes. For example, there was tight coordination of genes involved in the lower
      part of glycolysis, fatty acid synthesis and lipid production at dawn preceding
      lipid accumulation during the day. Our results suggest that diel lipid storage
      plays a key role for N. oceanica CCMP1779 growth under natural conditions making
      this alga a promising model to gain a basic mechanistic understanding of
      triacylglycerol production in photosynthetic cells. Our data will help the
      formulation of new hypotheses on the role of cyclic gene expression in cell
      growth and metabolism in Nannochloropsis. 

PMID- 26216535
TI  - Racial variation in adjuvant chemotherapy initiation among breast cancer patients
      receiving oncotype DX testing.
AB  - It is unknown whether racial differences exist in adjuvant chemotherapy
      initiation among women with similar oncotype DX (ODX) risk scores. We examined
      whether adjuvant chemotherapy initiation varied by race. Data come from the Phase
      III, Carolina Breast Cancer Study, a longitudinal, population-based study of
      North Carolina women diagnosed with breast cancer between 2008 and 2014. We used
      modified Poisson regression and report adjusted relative risk (aRR) and 95%
      confidence intervals (95%CI) to estimate the association between race and
      adjuvant chemotherapy initiation across ODX risk groups among women who received
      the test (n = 541). Among women who underwent ODX testing, 54.2, 37.5, and 8.3%
      of women had tumors classified as low-, intermediate-, and high-risk groups,
      respectively. We observed no racial variation in adjuvant chemotherapy
      initiation. Increasing ODX risk score (aRR = 1.39, 95%CI = 1.22, 1.58) and being
      married (aRR = 2.92, 95%CI = 1.12, 7.60) were independently associated with an
      increased likelihood of adjuvant chemotherapy in the low-risk group. Among women
      in the intermediate-risk group, ODX risk score (aRR = 1.15, 95%CI = 1.11, 1.20),
      younger age (aRR = 1.95, 95%CI = 1.35, 2.81), larger tumor size (aRR = 1.70,
      95%CI = 1.22, 2.35), and higher income were independently associated with
      increased likelihood of adjuvant chemotherapy initiation. No racial differences
      were found in adjuvant chemotherapy initiation among women receiving ODX testing.
      As treatment decision-making becomes increasingly targeted with the use of
      genetic technologies, these results provide evidence that test results may drive
      treatment in a similar way across racial subgroups.

PMID- 26216536
TI  - The challenging differential diagnosis of skin tumours with a rhabdoid phenotype:
      not all tumours with rhabdoid phenotype belong to the group of SMARCB1-deficient
      tumours.

PMID- 26216537
TI  - A set of domain-specific markers in the Arabidopsis embryo.
AB  - KEY MESSAGE: We describe a novel set of domain-specific markers that can be used
      in genetic studies, and we used two examples to show loss of stem cells in a
      monopteros background. Multicellular organisms can be defined by their ability to
      establish distinct cell identities, and it is therefore of critical importance to
      distinguish cell types. One step that leads to cell identity specification is
      activation of unique sets of transcripts. This property is often exploited in
      order to infer cell identity; the availability of good domain-specific marker
      lines is, however, poor in the Arabidopsis embryo. Here we describe a novel set
      of domain-specific marker lines that can be used in Arabidopsis (embryo)
      research. Based on transcriptomic data, we selected 12 genes for expression
      analysis, and according to the observed expression domain during embryogenesis,
      we divided them into four categories (1-ground tissue; 2-root stem cell; 3-shoot
      apical meristem; 4-post-embryonic). We additionally show the use of two markers
      from the "stem cell" category in a genetic study, where we use the absence of the
      markers to infer developmental defects in the monopteros mutant background.
      Finally, in order to judge whether the established marker lines also play a role
      in normal development, we generated loss-of-function resources. None of the
      analyzed T-DNA insertion, artificial microRNA, or misexpression lines showed any
      apparent phenotypic difference from wild type, indicating that these genes are
      not nonredundantly required for development, but also suggesting that marker
      activation can be considered an output of the patterning process. This set of
      domain-specific marker lines is therefore a valuable addition to the currently
      available markers and will help to move toward a generic set of tissue identity
      markers.

PMID- 26216538
TI  - Contrasting effects of warming and increased snowfall on Arctic tundra plant
      phenology over the past two decades.
AB  - Recent changes in climate have led to significant shifts in phenology, with many
      studies demonstrating advanced phenology in response to warming temperatures. The
      rate of temperature change is especially high in the Arctic, but this is also
      where we have relatively little data on phenological changes and the processes
      driving these changes. In order to understand how Arctic plant species are likely
      to respond to future changes in climate, we monitored flowering phenology in
      response to both experimental and ambient warming for four widespread species in
      two habitat types over 21 years. We additionally used long-term environmental
      records to disentangle the effects of temperature increase and changes in
      snowmelt date on phenological patterns. While flowering occurred earlier in
      response to experimental warming, plants in unmanipulated plots showed no change
      or a delay in flowering over the 21-year period, despite more than 1  degrees C
      of ambient warming during that time. This counterintuitive result was likely due
      to significantly delayed snowmelt over the study period (0.05-0.2 days/yr) due to
      increased winter snowfall. The timing of snowmelt was a strong driver of
      flowering phenology for all species - especially for early-flowering species -
      while spring temperature was significantly related to flowering time only for
      later-flowering species. Despite significantly delayed flowering phenology, the
      timing of seed maturation showed no significant change over time, suggesting that
      warmer temperatures may promote more rapid seed development. The results of this
      study highlight the importance of understanding the specific environmental cues
      that drive species' phenological responses as well as the complex interactions
      between temperature and precipitation when forecasting phenology over the coming
      decades. As demonstrated here, the effects of altered snowmelt patterns can
      counter the effects of warmer temperatures, even to the point of generating
      phenological responses opposite to those predicted by warming alone. 

PMID- 26216539
TI  - Disappearance of subocclusive ostial stenosis of the left anterior descending
      artery.

PMID- 26216540
TI  - [Treatment of acute heart failure].
AB  - Acute heart failure is a symptom complex of heterogeneous etiology. Clinically,
      it comprises a broad spectrum ranging from hypertensive pulmonary edema in
      patients with preserved left ventricular systolic function up to cardiogenic
      shock in patients with severely depressed left ventricular function. The
      pathophysiology of acute heart failure is based on a mismatch between myocardial
      pump function and afterload. Besides causal measures, vasodilators and diuretics
      are the mainstay of therapy. Catecholamines are indicated only when other drugs
      are unsuccessful. Opioids are often used in clinical practice but should be used
      cautiously as they are associated with a negative prognosis. Further adjunctive
      treatment consists of thromboembolism prophylaxis, non-invasive ventilation and
      in some cases mechanical circulatory support and renal replacement therapy. This
      article discusses the differential use of these treatment modalities. 

PMID- 26216541
TI  - [Assessment of progression and regression of coronary atherosclerosis by coronary
      angiography].
AB  - Quantitative coronary angiography (QCA) has been used for many years to study
      therapy effects. This became possible after a very high standardization of
      computer-assisted evaluation of coronary angiograms was introduced. The results
      of studies with various medications showed that the progression of coronary
      atherosclerosis could actually be inhibited. Reports on regression were rare and
      were in the range of 10 % of patients who showed such a response. In recent years
      only a few studies were carried out with QCA to test the effects of medications.
      Intravascular ultrasound is the new gold standard for recording coronary
      atherosclerosis. First rosuvastatin, later fluvastatin and simvastatin and
      recently rosuvastatin and atorvastatin were tested. Related to the progression
      and regression of coronary artery sclerosis, the data demonstrated that below a
      low-density lipoprotein (LDL) cholesterol threshold of 80 mg/dl patients
      developed regression and above this level progression was predominantly found.
      These results were similar to the studies using intravascular ultrasound;
      however, progression and regression are also related to the level of high density
      lipoprotein (HDL) cholesterol similar again to the level, which could be detected
      by intravascular ultrasound. Thus, not only intravascular ultrasound but also QCA
      should be used to study drug interactions with coronary atherosclerosis and
      particularly when new drugs are compared to statins. 

PMID- 26216543
TI  - Bioprinting for cancer research.
AB  - Bioprinting offers the ability to create highly complex 3D architectures with
      living cells. This cutting-edge technique has significantly gained popularity and
      applicability in several fields. Bioprinting methods have been developed to
      effectively and rapidly pattern living cells, biological macromolecules, and
      biomaterials. These technologies hold great potential for applications in cancer
      research. Bioprinted cancer models represent a significant improvement over
      previous 2D models by mimicking 3D complexity and facilitating physiologically
      relevant cell-cell and cell-matrix interactions. Here we review bioprinting
      methods based on inkjet, microextrusion, and laser technologies and compare 3D
      cancer models with 2D cancer models. We discuss bioprinted models that mimic the
      tumor microenvironment, providing a platform for deeper understanding of cancer
      pathology, anticancer drug screening, and cancer treatment development. 

PMID- 26216542
TI  - [Coronary atherosclerosis and progression to unstable plaques :
      Histomorphological and molecular aspects].
AB  - Atherosclerosis causes clinical symptoms through luminal narrowing by stenosis or
      by precipitating thrombi that obstruct blood flow to the myocardium (coronary
      artery disease), central nervous system (ischemic stroke) or lower extremities
      (peripheral vascular disease). The most common of these manifestations of
      atherosclerosis is coronary artery disease, clinically presenting as either
      stable angina or acute coronary syndromes. Atherosclerosis is a mainly
      lipoprotein-driven disease, which is associated with the formation of
      atherosclerotic plaques at specific sites of the vascular system through
      inflammation, necrosis, fibrosis and calcification. In most cases, plaque rupture
      of a so-called thin-cap fibroatheroma leads to contact of the necrotic core
      material of the underlying atherosclerotic plaque with blood, resulting in the
      formation of a thrombus with acute occlusion of the affected (coronary) artery.
      The atherosclerotic lesions that can cause acute coronary syndromes by formation
      of a thrombotic occlusion encompass (1) thin-cap fibroatheroma, (2) plaque
      erosion and (3) so-called calcified nodules in calcified and tortuous arteries of
      aged individuals. The underlying pathomechanisms remain incompletely understood
      so far. In this review, the mechanisms of atherosclerotic plaque initiation and
      progression are discussed. 

PMID- 26216544
TI  - Probiotic administration can prevent necrotizing enterocolitis in preterm
      infants: A meta-analysis.
AB  - PURPOSE: Necrotizing enterocolitis (NEC) is the most common gastrointestinal
      emergency in preterm infants, affecting ~6-7% of very-low-birth-weight (VLBW)
      infants. Early intervention and aggressive treatment has improved clinical
      outcomes, but considerable morbidity continues to accrue to NEC survivors. This
      meta-analysis examines the impact of probiotics on the incidence of NEC and
      complications among VLBW infants. METHODS: A comprehensive literature search for
      all published randomized control trials (RCTs) assessing the use of probiotics to
      prevent NEC in VLBW infants was conducted using PubMed, Cochrane Central Registry
      of Controlled Trials, and Google Scholar (1966-2014). The incidences of NEC,
      sepsis, overall mortality, and time to reach full enteral feeds were analyzed.
      RESULTS: 20 RCTs involving 5982 preterm VLBW infants were analyzed. Risk of NEC
      was reduced by 49.1% (RR=0.509; 95% CI, 0.385-0.672; p<0.001), and overall
      mortality by 26.9% among infants receiving probiotics (RR=0.731; 95% CI, 0.577
      0.926; p=0.009). An 8.1% reduction in sepsis was also observed in infants
      receiving probiotics (RR=0.919; 95% CI, 0.823-1.027; p=0.137). Time to reach full
      enteral feeds was reduced by 1.2 days among infants receiving probiotics (MD: 
      1.217; 95% CI, -2.151 to -0.283; p=0.011). CONCLUSION: The use of probiotic
      supplementation in preterm VLBW infants is associated with a significant
      reduction in the risk of NEC and overall mortality. Additional studies are
      required to determine the optimal genus, species, and dose of probiotic.

PMID- 26216545
TI  - Advances in the treatment of ocular dryness associated with Sjogren's syndrome.
AB  - BACKGROUND: Sjogren's syndrome (SS) is an autoimmune rheumatic disease that is
      characterised by decreased exocrine gland function and frequent ocular symptoms
      associated with eye dryness. Significantly, dry eyes can lead to corneal
      abrasions, infection, ulceration, chronic scarring and, in severe cases,
      perforation. The available conventional therapies have limited efficacy and there
      are no biologic therapies licensed for use in SS patients. MATERIALS AND METHODS:
      A literature search of PubMed (MEDLINE) and EMBASE electronic data bases was
      performed covering the period from January 1994 to September 2014. Evidence was
      graded in categories I-IV and a treatment algorithm, comprising first line,
      second line and rescue therapies for ocular dryness associated with SS was
      proposed. It is based on the current evidence of efficacy of different therapies
      and explores their link with the pathogenesis of ocular dryness associated with
      SS. RESULTS: Recent developments in the understanding of the pathogenesis of SS
      provided evidence that the ocular dryness is associated with pathologic
      infiltration and dysfunction of the lacrimal glands and changes in the tear
      composition, together with abnormalities involving the neurosecreting circuits.
      There is good evidence for the efficacy of topical artificial tears,
      antiinflammatories and Cyclosporine, and oral Pilocarpine and Cevimeline in
      controlling the symptoms of ocular dryness associated with SS. CONCLUSIONS:
      Conventional DMARDs are not particularly effective in addressing the symptoms of
      ocular dryness associated with SS, despite being commonly prescribed for other SS
      manifestations. Emerging evidence suggests that B cell and co-stimulatory
      targeted therapy may play a role in the future.

PMID- 26216546
TI  - Genomic sequence of the aflatoxigenic filamentous fungus Aspergillus nomius.
AB  - BACKGROUND: Aspergillus nomius is an opportunistic pathogen and one of the three
      most important producers of aflatoxins in section Flavi. This fungus has been
      reported to contaminate agricultural commodities, but it has also been sampled in
      non-agricultural areas so the host range is not well known. Having a similar
      mycotoxin profile as A. parasiticus, isolates of A. nomius are capable of
      secreting B- and G- aflatoxins. RESULTS: In this study we discovered that the A.
      nomius type strain (NRRL 13137) has a genome size of approximately 36 Mb which is
      comparable to other Aspergilli whose genomes have been sequenced. Its genome
      encompasses 11,918 predicted genes, 72% of which were assigned GO terms using
      BLAST2GO. More than 1,200 of those predicted genes were identified as unique to
      A. nomius, and the most significantly enriched GO category among the unique genes
      was oxidoreducatase activity. Phylogenomic inference shows NRRL 13137 as
      ancestral to the other aflatoxigenic species examined from section Flavi. This
      strain contains a single mating-type idiomorph designated as MAT1-1. CONCLUSIONS:
      This study provides a preliminary analysis of the A. nomius genome. Given the
      recently discovered potential for A. nomius to undergo sexual recombination, and
      based on our findings, this genome sequence provides an additional evolutionary
      reference point for studying the genetics and biology of aflatoxin production.

PMID- 26216547
TI  - Evaluation of School of health students' ethics position in Turkey.
AB  - BACKGROUND: The advances in science and technology increasingly lead to the
      appearance of ethical issues and to the complexity of care. Therefore, it is
      important to define the ethics position of students studying in health
      departments so that high quality patient care can be achieved. OBJECTIVES: The
      aim of this study was to examine the ethics position of the students at Shool of
      Health of an University in western Turkey. METHODS: The study design was
      descriptive and cross-sectional. The study population included 540 first, second,
      third, and fourth year students from the Departments of Nursing, Midwifery, and
      Rescue and Disaster Management in the 2013-2014 academic year. Data were
      collected with a Personal Identification Form and The Ethics Position
      Questionnaire. Obtained data were analyzed with Chi-square test, Confirmatory
      Factor Analysis, and Nested Analysis of Variance. Ethical considerations: Before
      conducting the research, approval was obtained from Ege University Clinical
      Research Ethics Committee in Izmir and written informed consent was taken from
      all the participants. FINDINGS: There was no significant difference in the mean
      scores for the Ethics Position Questionnaire between the students in terms of
      years and fields of study. Although the mean scores for the subscale idealism did
      not differ between fields of study, the mean scores significantly differed
      between years of study. However, the mean scores for the subscale relativism did
      not differ in terms of years and fields of study. DISCUSSION: Whether students
      are idealistic or relativistic in terms of ethical judgment will be effective in
      ethical decision-making skills during patient care. Therefore, we need to define
      the factors that influence students' ethics position in the future. CONCLUSION:
      It is suggested that the courses and practices that teach students to be aware of
      their ethics position to create an ethical outlook can be placed in the
      curriculum in health schools.

PMID- 26216548
TI  - Pulsed High-Intensity Focused Ultrasound Enhances Delivery of Doxorubicin in a
      Preclinical Model of Pancreatic Cancer.
AB  - Pancreatic cancer is characterized by extensive stromal desmoplasia, which
      decreases blood perfusion and impedes chemotherapy delivery. Breaking the stromal
      barrier could both increase perfusion and permeabilize the tumor, enhancing
      chemotherapy penetration. Mechanical disruption of the stroma can be achieved
      using ultrasound-induced bubble activity-cavitation. Cavitation is also known to
      result in microstreaming and could have the added benefit of actively enhancing
      diffusion into the tumors. Here, we report the ability to enhance
      chemotherapeutic drug doxorubicin penetration using ultrasound-induced cavitation
      in a genetically engineered mouse model (KPC mouse) of pancreatic ductal
      adenocarcinoma. To induce localized inertial cavitation in pancreatic tumors,
      pulsed high-intensity focused ultrasound (pHIFU) was used either during or before
      doxorubicin administration to elucidate the mechanisms of enhanced drug delivery
      (active vs. passive drug diffusion). For both types, the pHIFU exposures that
      were associated with high cavitation activity resulted in disruption of the
      highly fibrotic stromal matrix and enhanced the normalized doxorubicin
      concentration by up to 4.5-fold compared with controls. Furthermore, normalized
      doxorubicin concentration was associated with the cavitation metrics (P < 0.01),
      indicating that high and sustained cavitation results in increased chemotherapy
      penetration. No significant difference between the outcomes of the two types,
      that is, doxorubicin infusion during or after pHIFU treatment, was observed,
      suggesting that passive diffusion into previously permeabilized tissue is the
      major mechanism for the increase in drug concentration. Together, the data
      indicate that pHIFU treatment of pancreatic tumors when resulting in high and
      sustained cavitation can efficiently enhance chemotherapy delivery to pancreatic
      tumors. .

PMID- 26216549
TI  - miR-634 Activates the Mitochondrial Apoptosis Pathway and Enhances Chemotherapy
      Induced Cytotoxicity.
AB  - Some tumor-suppressing miRNAs target multiple oncogenes concurrently and
      therefore may be useful as cancer therapeutic agents. Further, such miRNAs may be
      useful to address chemotherapeutic resistance in cancer, which remains a primary
      clinical challenge in need of solutions. Thus, cytoprotective processes
      upregulated in cancer cells that are resistant to chemotherapy are a logical
      target for investigation. Here, we report that overexpression of miR-634
      activates the mitochondrial apoptotic pathway by direct concurrent targeting of
      genes associated with mitochondrial homeostasis, antiapoptosis, antioxidant
      ability, and autophagy. In particular, we show how enforced expression of miR-634
      enhanced chemotherapy-induced cytotoxicity in a model of esophageal squamous cell
      carcinoma, where resistance to chemotherapy remains clinically problematic. Our
      findings illustrate how reversing miR-634-mediated cytoprotective processes may
      offer a broadly useful approach to improving cancer therapy.

PMID- 26216550
TI  - The effect of light emitting diode phototherapy on rate of orthodontic tooth
      movement: a split mouth, controlled clinical trial.
AB  - OBJECTIVE: Increasing the rate of orthodontic tooth movement (OTM) can reduce
      risks such as periodontal disease and caries. TRIAL DESIGN: This split-mouth
      randomized controlled clinical trial investigated whether light emitting diode
      (LED) phototherapy could accelerate the rate of OTM. SETTING: The study was
      conducted at the Graduate Orthodontics Clinic at the University of Toronto,
      Faculty of Dentistry. PARTICIPANTS AND METHODS: 17 dental arches from 11
      orthodontic participants with bilaterally symmetrical extraction of premolars
      were included. During space closure of single tooth extraction sites, LED
      phototherapy was applied to one side of the dental arch for a specified time and
      the contralateral side acted as the control. Space closure was measured
      immediately prior to, during and later in space closure. RESULTS: All
      participants were compliant with LED application. Our results revealed no
      significant changes in the rate of OTM with LED phototherapy over 3 months of
      extraction space closure. CONCLUSIONS: Our findings were contrary to previous
      findings of the effect of laser phototherapy on regulating the rate of OTM.
      Further investigations are warranted to analyse whether the duration or method of
      LED delivery would have an effect on the rate of OTM. Toronto. This trial was
      registered at clinicaltrials.gov (NCT01490385).

PMID- 26216551
TI  - Electrochemical characterization and in-vitro bio-assessment of AZ31B and AZ91E
      alloys as biodegradable implant materials.
AB  - The degradation of magnesium alloys, AZ31B and AZ91E, are under review due to a
      their ability to degrade under physiological conditions and successively yield an
      oxidized biocompatible by-product which can safely be absorbed by the body. By
      exploiting the biodegradability of magnesium alloys, the prospects of developing
      an unprecedented class of implant are at hand. To do so however, the rate of
      corrosion of the alloys must be modified in order to better suit physiological
      conditions. Therefore, anodization was carried out on AZ31B and AZ91E specimens
      to alter the surface chemistry to reduce the corrosion rates and improve
      biocompatibility. Scanning electron microscopy, energy dispersive spectroscopy,
      atomic force microscopy and contact angle meter, were used to characterize and
      compare the surfaces of untreated and anodized magnesium alloys. Corrosion
      behavior was evaluated by electrochemical tests using potentiodynamic
      polarization and electrochemical impedance spectroscopy, to verify changes in
      corrosion rates as a result of anodization. Finally, a bio-assessment using MTS
      assays and fluorescent microscopy were carried out to ensure that the anodization
      process had no compromise on the biocompatibility of the magnesium alloys. The
      study indicated that the anodization process did alter the surface chemistry of
      the alloys, yielding slower corrosion rates, while causing no adverse effects in
      regards to biocompatibility. 

PMID- 26216553
TI  - Novel psychoactive substances: second and third international conferences.

PMID- 26216552
TI  - Micro-structural analysis of NiFe2O4 nanoparticles synthesized by thermal plasma
      route and its suitability for BSA adsorption.
AB  - The paper presents the experimental studies pertaining to the adsorption of
      bovine serum albumin (BSA) on the nanoparticles of nickel ferrite (NiFe2O4) with
      a view of correlating the adsorption properties to their microstructure and zeta
      potentials. Physical properties of two kinds of nickel ferrites, one synthesized
      by thermal plasma route and the other by chemical co-precipitation method, are
      compared. Maximum adsorption (231.57 MUg/mg) of BSA onto nickel ferrite
      nanoparticles, at body temperature (37  degrees C) was observed at pH-value of
      5.58 for the thermal plasma synthesized particles showing its higher adsorption
      capacity than those synthesized by wet chemical means (178.71 MUg/mg). Under the
      same physical conditions the value of zeta potential, obtained for the former,
      was higher than that of the latter over a wide range of pH values (3.64-9.66).
      This is attributed to the differences in the specific surface energies of the two
      kinds of nanoparticles arising from the degree of crystallinity. The paper
      presents the experimental evidence for the single crystalline nature of the
      individual nanoparticles, with mean size of 32 nm, for the thermal plasma
      synthesized particles as evidenced from the high resolution transmission electron
      microscopy and electron diffraction analysis. The measurements also reveal the
      poor crystalline morphology in the chemically prepared particles (mean size of 28
      nm) although the X-ray diffraction patterns are not much different. The atomic
      force microscopy images confirm that the surfaces of plasma synthesized
      nanoparticles possesses higher surface roughness than that of chemically
      synthesized one. Presence of adsorbed protein was confirmed by vibrational
      spectroscopy. The Langmuir adsorption model is found to fit into the experimental
      data better than the Freundlich adsorption model. 

PMID- 26216554
TI  - Why all stimulant drugs are damaging to recreational users: an empirical overview
      and psychobiological explanation.
AB  - AIMS: Stimulant drugs such as nicotine and Ecstasy/3, 4
      methylenedioxymethamphetamine (MDMA) are taken for positive reasons, yet their
      regular use leads to deficits rather than gains. This article outlines the
      psychobiological rationale for this paradox. METHODS: The empirical literature on
      nicotine, cocaine, amphetamine, Ecstasy/MDMA, and mephedrone are reviewed. A
      theoretical explanation for why they are problematic to humans is then described.
      RESULTS: The acute effects of central nervous system (CNS) stimulants are
      typically positive, with greater alertness and emotional intensity. However, in
      the post-drug recovery period, the opposite feelings develop, with lethargy and
      low moods. All recreational stimulants cause mood fluctuation, although it is
      most pronounced in drugs with rapid onset and comedown (e.g. nicotine and
      cocaine), explaining why they are the most addictive. Parallel fluctuations occur
      across many psychological and neurocognitive functions, with users suffering
      various off-drug deficits. CNS stimulants also affect the hypothalamic-pituitary
      adrenal axis, impairing sleep, disrupting homeostasis, and exacerbating
      psychiatric distress. Neuroimaging studies reveal altered brain activity patterns
      in regular users. These problems are related to lifetime usage but commence in
      novice users. CONCLUSIONS: Repetitive CNS stimulation is potentially damaging to
      the organism, both acutely and chronically. The review describes the various
      psychobiological systems through which recreational stimulant drugs impair human
      well-being.

PMID- 26216555
TI  - Deaths of individuals aged 16-24 years in the UK after using mephedrone.
AB  - OBJECTIVE: Mephedrone is a stimulant drug chemically related to amphetamine, with
      effects similar to those of amphetamine and cocaine. This study aims to analyse
      fatalities following ingestion of mephedrone in the UK amongst 16- to 24-year
      olds in 2009-2013, providing an update on data presented at the 2nd International
      Conference on Novel Psychoactive Substances. METHODS: A literature search was
      undertaken to identify published information on pharmacology, toxicity and
      fatalities associated with mephedrone. Fatalities involving mephedrone were
      extracted from the National Programme on Substance Abuse Deaths database, which
      receives information on drug-related deaths from coroners in the UK and Islands
      and other data suppliers. Selection criteria are as follows: deceased aged 16-24
      years at time of death and mephedrone directly implicated in the cause of death
      and/or mentioned in the coroner's verdict. RESULTS: Thirty cases met the study
      criteria, and when known, all were of White ethnicity, most (85%) had a history
      of drug use and 73% were male. Two-thirds (63%) were accidental poisonings.
      Mephedrone was used with other substances in most cases (87%); other substances
      were implicated in 60% of deaths. CONCLUSIONS: Mephedrone use can have
      potentially fatal consequences, especially in combination with other substances.
      Deaths from its use in the 16-24 years' age group continue to occur in the UK,
      despite it being a controlled drug. Health professionals and potential consumers
      should be alert to this risk.

PMID- 26216556
TI  - Is there any difference in patterns of use and psychiatric symptom status between
      injectors and non-injectors of mephedrone?
AB  - OBJECTIVE: In recent years, increasing intravenous mephedrone use was reported in
      several countries. The aim of this study was to describe the characteristics of
      such a form of mephedrone use, while identifying the differences between
      injectors and non-injectors in patterns of mephedrone use and psychiatric symptom
      status. METHODS: One hundred and forty-five mephedrone users were surveyed on
      patterns of mephedrone use using a structured questionnaire as well as the Brief
      Symptom Inventory. RESULTS: Majority of users received mephedrone from
      acquaintances and used it in discos/parties settings regarding both first and
      current mephedrone use. Intranasal use was the most typical route of
      administration (84.4%). Injectors (11%) used the drug more frequently and in
      higher dosages. This group included a greater proportion of opiate users (37.5%)
      and showed more diffuse psychiatric symptoms. Regarding the predictors of being
      an injector, heroin use showed the highest odds ratio. CONCLUSIONS: Intravenous
      mephedrone use is associated with a higher risk of harmful drug use, elevated
      psychiatric symptom profile and increased possibility of mephedrone being
      considered as an addictive substance. These findings might be important in
      efficient treatment planning.

PMID- 26216557
TI  - Methoxetamine-related deaths in the UK: an overview.
AB  - OBJECTIVE: The goal of this study is to provide an update on the data given on
      methoxetamine (MXE)-related fatalities that occurred in 2011-2013, presented at
      the Second International Conference on Novel Psychoactive Substances. METHODS:
      Fatalities involving MXE were extracted from the database of the National
      Programme on Substance Abuse Deaths, which receives information on drug-related
      deaths from Coroners in the UK and Islands (Isle of Man, Jersey, Guernsey) and
      other data suppliers. RESULTS: Eight cases, received by 3 September 2013, in
      which MXE was found at post-mortem and/or directly implicated in the death and/or
      mentioned in the Coroner's verdict are described. The median age at death was 27
      years, with the majority of White ethnicity (6/8) and male (7/8). MXE was used
      together with other substances in 7/8 cases. MXE was found at post-mortem in all
      cases, directly implicated in the deaths of four and likely to have had an
      influence in two. CONCLUSIONS: More research needs to be conducted into its
      health effects and toxicity potential. Health care professionals should be made
      aware of the potential health harms of MXE, in order to develop early
      intervention measures and minimise the number of MXE-related poisonings and
      fatalities.

PMID- 26216558
TI  - Olanzapine as the ideal "trip terminator"? Analysis of online reports relating to
      antipsychotics' use and misuse following occurrence of novel psychoactive
      substance-related psychotic symptoms.
AB  - OBJECTIVE: The pharmacological self-management of novel psychoactive substance
      (NPS)-induced psychopathological consequences represents a fast growing
      phenomenon. This is facilitated by the frequent sharing of NPS intake experiences
      online and by the ease of access to a range of psychotropic medications from both
      the online and street market. Olanzapine is anecdotally reported by Web users to
      be the most frequent self-prescribed medication to cope with NPS-induced
      psychoses. Hence, we aimed here at better assessing olanzapine use/misuse for
      this purpose. METHODS: Exploratory qualitative searches of 163 discussion
      fora/specialized websites have been carried out in four languages (English,
      German, Spanish, and Italian) in the time frame November 2012-2013. RESULTS: Most
      NPS-users allegedly self administer with olanzapine to manage related psychotic
      crises/"bad trips". This may be typically taken only for a few days, at a dosage
      range of 5-50 mg/day. CONCLUSIONS: Only a few research studies have formally
      assessed the effectiveness of olanzapine and indeed of other second-generation
      antipsychotics to treat NPS-induced psychosis. Olanzapine was suggested here from
      a range of pro drug websites as being the "ideal" molecule to terminate "bad
      trips". Health professionals should be informed about the risks related to
      olanzapine misuse.

PMID- 26216559
TI  - Venlafaxine as the 'baby ecstasy'? Literature overview and analysis of web-based
      misusers' experiences.
AB  - INTRODUCTION: Venlafaxine is one of the most frequently prescribed
      antidepressants worldwide, despite its toxicity risk in overdose. Furthermore,
      the molecule has been recently identified at the EU-wide level as one of the
      novel psychoactive substances. This paper aims at investigating the potential of
      misuse, taking into account both the existing literature and the analysis of the
      misusers' experiences as described in venlafaxine misuse web reports. METHODS: A
      literature search was performed using PubMed, Embase, and Medline. Posts/threads
      relating to venlafaxine misuse issues were identified through Google(r) and
      Yahoo(r) English-language searches. Resulting websites' data were then
      qualitatively assessed, and information was collected on a range of issues,
      including dosage, drug intake modalities, untoward drug effects, and association
      with other recreational drugs. RESULTS: A few literature case reports focusing on
      venlafaxine as a misusing drug were here identified. The molecule was here
      typically ingested or snorted at dosages up to 10-15 times higher than those
      clinically advised, obtaining MDMA/amphetamine-like stimulant and psychedelic
      effects. Polydrug misuse was commonly reported. Venlafaxine appeared to be widely
      available online for sale. CONCLUSIONS: Physicians should carefully evaluate
      patients for history of drug dependence and observe them for signs of venlafaxine
      misuse.

PMID- 26216560
TI  - Injecting eye-drops: a mini-review on the non-clinical use of tropicamide.
AB  - OBJECTIVES: The intravenous (IV) injection of tropicamide for non-clinical
      purposes is a new and widespread drug trend. The aim of this study is to provide
      the first literature review on the topic. METHODS: Relevant literature was
      identified through a search of MEDLINE, Psycinfo, Google Scholar, conference
      proceedings and select citations. RESULTS: Cases of tropicamide (IV) injection
      have been reported in Russia, Italy, Turkey and Kazakhstan. This phenomenon is
      mainly secondary to primary opioid (especially heroin) addiction. Several key
      factors can be associated with its rapid diffusion: (i) enhancement of the
      'positive' effects of heroin; (ii) decrease and delay of heroin withdrawal
      symptoms; (iii) easy availability; (iv) low costs; (v) fast effects; and (vi)
      visibility of self-reported experiences on Internet. Acute tropicamide
      intoxications can lead to anticholinergic syndrome, hyperthermia, tremors and
      convulsions. Chronic tropicamide-related problems include cardiovascular
      toxicity, psychosis, renal or liver failures, severe weight loss and infections.
      Fatalities due to tropicamide IV injection have been reported in non evidence
      based/peer-reviewed sources, such as drug fora, websites and media news.
      CONCLUSIONS: Tropicamide IV injections represent a serious health risk. Specific
      prevention programmes should be implemented for the general population as well as
      for the high-risk population of polydrug abusers.

PMID- 26216561
TI  - Psyclones: a roller coaster of life? Hidden synthetic cannabinoids and stimulants
      in apparently harmless products.
AB  - OBJECTIVE: The urge to gain information on a new drug marketed online as
      'Psyclone' has emerged after the death of a 38-year-old man in Bolton (UK). The
      fatality appeared to be a consequence of smoking this psychoactive product.
      METHODS: From October to December 2013, qualitative searches of the Web have been
      carried out in English and Italian, using the keywords 'Psyclone', 'Psyclone
      legal high', 'Psyclone incense' and 'Psyclone research chemical' on the Google
      search engine and on the database provided by the Global Public Health
      Intelligence Network. RESULTS: Our research highlighted the existence of two
      psychoactive products labelled as Psyclone but with different contents and
      packaging: a herbal blend containing two synthetic cannabinoids (AKB-48 and 5f-PB
      22) and a research chemical containing 50% ethylphenidate, 30% caffeine and 20%
      lidocaine. Desired and side effects of both compounds are explored in the paper.
      CONCLUSIONS: Being sold as a legal product, Psyclone may appeal to recreational
      users, who remain unaware of its real content. This is a serious public health
      threat, which may lead to acute intoxications and fatalities. Further studies in
      the field, including Internet monitoring, are therefore required.

PMID- 26216562
TI  - Greater sexual risk-taking in female and male recreational MDMA/ecstasy users
      compared with alcohol drinkers: a questionnaire study.
AB  - AIMS: Previous studies have shown increased sexual risk-taking in experienced
      MDMA/ecstasy users. The main objectives of this study were to compare levels of
      sexual risk-taking between a young student sample of predominantly heterosexual
      MDMA users and alcohol-drinker controls and investigate potential gender
      differences. METHODS: Recreational drug use and sexual risk questionnaires were
      completed by 20 MDMA users (10 females, 10 males) and 20 non-user controls (10
      females, 10 males). They were predominantly university students, aged between 20
      22 years, mainly heterosexual (n = 37), with three bisexual participants.
      RESULTS: MDMA users displayed significantly greater levels of sexual risk-taking
      than the alcohol-drinker controls. It involved significantly higher rates of
      casual sex, non-condom use during sex, and penetrative sexual risks. This
      increase in sexual riskiness occurred to a similar extent in males and females.
      CONCLUSIONS: These findings indicate that both female and male ecstasy/MDMA users
      reported more risky sexual behaviours, than the non-user controls. Further
      research into the sexual behaviour and sexual risk-taking of heterosexual MDMA
      users should be conducted because much of the past literature has focused on
      homosexual participants.

PMID- 26216563
TI  - Enhancing sexual desire and experience: an investigation of the sexual correlates
      of gamma-hydroxybutyrate (GHB) use.
AB  - OBJECTIVE: Various studies have dealt with gamma-hydroxybutyrate's (GHB)
      potential role in sexual assaults, while the sexual correlates of intentional
      recreational GHB use have not well been highlighted. Our study aims to explore
      GHB's sexual effects, the patterns of choice of sexual partners, the frequency of
      experienced blackouts, and endured sexual or acquisitory crimes as a result of
      GHB use. METHODS: Sixty recreational GHB users filled out a questionnaire on
      experienced subjective, somatic, and sexual effects of GHB, the frequency of
      blackouts due to their GHB use, and items on their sexual experiences in relation
      to GHB use. RESULTS: Of the sample, 25.9% reported increased sexual arousal as
      well as more intense attraction towards their sexual partners and increased
      sexual openness when using GHB; 34.8% had sexual intercourse with strangers, or
      with others, but not with their partners when using GHB; and 8.6% were victims of
      acquisitory crimes, whereas 3.4% were victims of a sexual assault. Furthermore,
      24.6% typically experienced blackouts when using GHB. CONCLUSION: Gamma
      hydroxybutyrate seems to be a potential substitute for both stimulant and
      depressant substances. Increased sexual desire and disinhibition may lead to a
      more frequent and potentially more riskful sexual activity. Experienced blackouts
      need to be considered as risk factors for suffering sexual or acquisitory crimes.

PMID- 26216564
TI  - Prenatal cocaine exposure and child outcomes: a conference report based on a
      prospective study from Cleveland.
AB  - OBJECTIVE: The study aims to describe developmental outcomes from a longitudinal
      prospective cohort (Cleveland study) of prenatally cocaine-exposed (CE) infants.
      METHODS: Two hundred eighteen CE and 197 nonexposed infants were enrolled at
      birth and followed through mid-adolescence. Birth CE status was determined by
      interview and biologic measures. Multiple demographic, drug, and environmental
      correlates were controlled. Standardized, normative, reliable measures of fetal
      growth, intelligence quotient (IQ), behavior, executive function, and language
      were given at each age and risk for substance misuse assessed in adolescence. A
      subset of children received volumetric magnetic resonance imaging (MRI) at 7
      years and functional MRI at 14 years. The effect of CE was determined through
      multiple regression analyses controlling for confounders. RESULTS: Cocaine
      exposed had significant negative effects on fetal growth, attention, executive
      function, language, and behavior, while overall IQ was not affected. CE had
      significant negative effects on perceptual reasoning IQ and visual-motor skills
      and predicted lower volume of corpus callosum and decreased gray matter in the
      occipital and parietal lobes. CE children had higher risk for substance misuse.
      Confounding risk factors had additive effects on developmental outcomes.
      CONCLUSIONS: Prenatal exposure to cocaine was related to poorer perceptual
      organization IQ, visual-spatial information processing, attention, language,
      executive function, and behavior regulation through early adolescence.

PMID- 26216565
TI  - Developmental outcomes of 3,4-methylenedioxymethamphetamine (ecstasy)-exposed
      infants in the UK.
AB  - OBJECTIVE: This paper aims to review findings from a longitudinal study of
      prenatal methylenedioxymethamphetamine (MDMA, "ecstasy") on infant development.
      METHODS: In a prospective, longitudinal cohort design, we followed 28 MDMA
      exposed and 68 non-MDMA-exposed infants from birth to 2 years of age. Women
      recruited voluntarily into a study of recreational drug use during pregnancy were
      interviewed to obtain type, frequency, and amount of recreational drug use. Their
      children were followed for a 2-year period after birth. A large number of drug
      and environmental covariates were controlled. Infants were seen at 1, 4, 12, 18,
      and 24 months using standardized normative tests of mental and motor development.
      RESULTS: There were no differences between MDMA-exposed and non-MDMA-exposed
      infants at birth except that MDMA-exposed infants were more likely to be male.
      Motor delays were evident in MDMA infants at each age and amount of MDMA exposure
      predicted motor deficits at 12 months in a dose-dependent fashion. CONCLUSIONS:
      Prenatal MDMA exposure is related to fine and gross motor delays in the first 2
      years of life. Follow-up studies are needed to determine long-term effects.

PMID- 26216566
TI  - Novel psychoactive substances: use and knowledge among adolescents and young
      adults in urban and rural areas.
AB  - INTRODUCTION: Novel psychoactive substances (NPS) are new psychotropic drugs, not
      scheduled under the International Conventions on Psychotropic Substances, but
      which may pose a relevant public health threat. In this study, we investigated
      knowledge and use of NPS in a sample of Italian youth in urban and rural areas.
      METHODS: Between December 2012 and October 2013, we administered a questionnaire
      to a sample of 3011 healthy subjects (44.7% men; 55.3% women), aged between 16
      and 24 years and recruited in urban, intermediate and rural areas of Italy.
      RESULTS: Of the global sample, 53.3% declared to have some knowledge on NPS, with
      a higher knowledge in urban areas. Mephedrone (26%), desomorphine (22.6%) and
      methamphetamine (21.7%) were the most commonly known drugs. NPS use was reported
      by 4.7% of the sample, without significant differences between urban and rural
      areas; mephedrone (3.3%), synthetic cannabinoids (1.2%) and Salvia divinorum
      (0.3%) consumption has been identified. NPS use was also predictive of binge
      drinking behaviours (chi(2) (4) = 929.58, p < .001). DISCUSSION: Urban areas may
      represent a focal point for preventive strategies, given the presence of higher
      levels of NPS knowledge. Moreover, the association between binge-drinking habits
      and NPS use was really strong. This issue should not be underestimated because of
      its medical, psychopathological and social consequences.

PMID- 26216567
TI  - Profiling online recreational/prescription drugs' customers and overview of drug
      vending virtual marketplaces.
AB  - OBJECTIVES: Internet and social networking sites play a significant role in the
      marketing and distribution of recreational/prescription drugs without
      restrictions. We aimed here at reviewing data relating to the profile of the
      online drug customer and at describing drug vending websites. METHODS: The
      PubMed, Google Scholar, and Scopus databases were searched here in order to
      elicit data on the socio-demographic characteristics of the recreational
      marketplaces/online pharmacies' customers and the determinants relating to online
      drug purchasing activities. RESULTS: Typical online recreational drugs' customers
      seem to be Caucasian, men, in their 20s, highly educated, and using the web to
      impact as minimally as possible on their existing work/professional status.
      Conversely, people without any health insurance seemed to look at the web as a
      source of more affordable prescription medicines. Drug vending websites are
      typically presented here with a "no prescription required" approach, together
      with aggressive marketing strategies. CONCLUSIONS: The online availability of
      recreational/prescriptions drugs remains a public health concern. A more precise
      understanding of online vending sites' customers may well facilitate the drafting
      and implementation of proper prevention campaigns aimed at counteracting the
      increasing levels of online drug acquisition and hence intake activities.

PMID- 26216568
TI  - Detecting a signal in the noise: monitoring the global spread of novel
      psychoactive substances using media and other open-source information.
AB  - OBJECTIVE: To determine the feasibility and utility of using media reports and
      other open-source information collected by the Global Public Health Intelligence
      Network (GPHIN), an event-based surveillance system operated by the Public Health
      Agency of Canada, to rapidly detect clusters of adverse drug events associated
      with 'novel psychoactive substances' (NPS) at the international level. METHODS
      AND RESULTS: Researchers searched English media reports collected by the GPHIN
      between 1997 and 2013 for references to synthetic cannabinoids. They screened the
      resulting reports for relevance and content (i.e., reports of morbidity and
      arrest), plotted and compared with other available indicators (e.g., US poison
      control center exposures). The pattern of results from the analysis of GPHIN
      reports resembled the pattern seen from the other indicators. CONCLUSIONS: The
      results of this study indicate that using media and other open-source information
      can help monitor the presence, usage, local policy, law enforcement responses,
      and spread of NPS in a rapid effective way. Further, modifying GPHIN to actively
      track NPS would be relatively inexpensive to implement and would be highly
      complementary to current national and international monitoring efforts.

PMID- 26216570
TI  - Surgical management of chronic pancreatitis: current utilization in the United
      States.
AB  - BACKGROUND: Surgical intervention is uncommon in chronic pancreatitis. Literature
      largely describes single institution or international experiences. This study
      describes US-based chronic pancreatitis surgical management. METHODS:
      Retrospective analysis of chronic pancreatitis patients in the Healthcare Cost
      and Utilization Project Florida State Inpatient Database 2007-2011. Patients with
      malignancy or congenital abnormalities were excluded. Univariate analysis using
      the chi-square test. The number of readmissions, inpatient length of stay and
      cost using Wilcoxon's signed-rank test. Multivariate analysis of surgery by
      logistic regression. RESULTS: Twenty-one thousand four hundred and forty-five
      patients with chronic pancreatitis. 10.8% (2 307) underwent surgery including
      1652 cholecystectomies, 564 drainage procedures and 498 pancreatectomies.
      Procedures decreased from 12.1% to 8.3% over time (P < 0.001), but intervention
      within 3 months increased (7.2% to 8.4%; P = 0.017). 15.3% (3 278) had pancreatic
      cysts/pseudocysts and 43.4% (9 312) had diabetes. The median numbers of
      admissions were 2 [interquartile range (IQR) 1,5] and 3 (IQR 2,7) among non
      surgical and surgical patients, respectively (P < 0.001). Predictors of surgery
      were fewer co-morbidities, private insurance, and either diabetes mellitus or
      pancreatic cyst/pseudocyst. CONCLUSION: Chronic pancreatitis leads to numerous
      inpatient readmissions, but surgical intervention only occurs in a minority of
      cases. Complicated patients are more likely to undergo surgery. The complexities
      of chronic pancreatitis management warrant early multidisciplinary evaluation and
      ongoing consideration of surgical and non-surgical options.

PMID- 26216572
TI  - Relative response of the alanine dosimeter to medium energy x-rays.
AB  - The response of the alanine dosimeter to kilovoltage x-rays with respect to the
      dose to water was measured, relative to the response to Co-60 radiation.Two
      series of x-ray qualities were investigated, one ranging from 30 kV to 100 kV
      tube voltage (TW series), the other one ranging from 70 kV to 280 kV (TH series).
      Due to the use of the water calorimeter as a primary standard, the uncertainty of
      the delivered dose is significantly lower than for other published data. The
      alanine response was measured as described in a previous publication (Anton et al
      2013 Phys. Med. Biol. 58 3259-82). The uncertainty component due to the alanine
      measurement and analysis is ?0.4%, the major part of the combined uncertainty of
      the relative response originates from the uncertainty of the delivered dose. The
      relative uncertainties of the relative response vary from ?2% for the TW series
      to ?1.1% for the TH series.Different from the behaviour of the alanine dosimeter
      for megavoltage x-rays or electrons, the relative response drops significantly
      from unity for Co-60 radiation to less than 64% for the TW quality with a tube
      voltage of 30 kV. In order to reproduce this behaviour through Monte Carlo
      simulations, not only the ratio of the absorbed dose to alanine to the absorbed
      dose to water has to be known, but also the intrinsic efficiency, i.e. the
      dependence of the number of free radicals generated per unit of absorbed dose on
      the photon energy. This quantity is not yet accessible for the TW series.For a
      possible use of the alanine dosimeter for kilovoltage x-rays, for example in
      electronic brachytherapy, users should rely on the measured data for the relative
      response which have become available with this publication.

PMID- 26216571
TI  - IOP telemetry in the nonhuman primate.
AB  - This review is focused on continuous IOP monitoring using telemetry systems in
      the nonhuman primate (NHP), presented in the context that IOP fluctuations at
      various timescales may be involved in glaucoma pathogenesis and progression. We
      use glaucoma as the primary framework to discuss how the dynamic nature of IOP
      might change with age, racial heritage, and disease in the context of glaucoma
      susceptibility and progression. We focus on the limited work that has been
      published in IOP telemetry in NHPs, as well as the emerging data and approaches.
      We review the ongoing efforts to measure continuous IOP, and the strengths,
      weaknesses and general pitfalls of the various approaches. 

PMID- 26216573
TI  - Natural products as biofuels and bio-based chemicals: fatty acids and
      isoprenoids.
AB  - Although natural products are best known for their use in medicine and
      agriculture, a number of fatty acid-derived and isoprenoid natural products are
      being developed for use as renewable biofuels and bio-based chemicals. This
      review summarizes recent work on fatty acid-derived compounds (fatty acid alkyl
      esters, fatty alcohols, medium- and short-chain methyl ketones, alkanes, alpha
      olefins, and long-chain internal alkenes) and isoprenoids, including hemiterpenes
      (e.g., isoprene and isopentanol), monoterpenes (e.g., limonene), and
      sesquiterpenes (e.g., farnesene and bisabolene).

PMID- 26216575
TI  - A new HLA-A allele, HLA-A* 02:01:119, identified in a Chinese individual.
AB  - The new allele A*02:01:119 was initially identified in a Chinese individual by
      sequence-based typing. 

PMID- 26216576
TI  - pH and Erosive Potential of Commonly Used Oral Moisturizers.
AB  - PURPOSE: To measure the pH values of commonly used oral moisturizers and to
      evaluate their erosive potential using a gravimetric analysis. MATERIALS AND
      METHODS: A pH analysis was performed for seven commercially available oral
      moisturizers using a calibrated pH meter. The pH recording was repeated three
      times, from three different bottles each of the same product. The gravimetric
      analysis was performed by submerging human dentin blocks in 5 ml of each of the
      moisturizers for a total of 2 weeks, with gravimetric measurements made at
      baseline, 24 hours, 48 hours, 96 hours, 1 week, and 15 days. Tap water was used
      as positive control and citric acid as the negative control. The erosive
      potential was descriptively analyzed, and a Spearman correlation coefficient was
      used to assess the relationship between the erosive potential and the pH values.
      RESULTS: The average pH values are as follows: Oasis, 6.3, Biotene Moisturizing
      Mouth Spray, 6.1, CTx2 Spray, 9.1, Mouth Kote, 3.0, Thayer's, 6.3, Biotene Oral
      Balance, 6.6, Rain, 7.1, tap water 6.99, and citric acid 1.33. The results (% of
      tooth structure lost) of the gravimetric analysis were as follows: Mouth Kote,
      9.6%, Biotene Moisturizing Mouth Spray, 4.6%, Oasis, 3.2%, Thayer's, 2.0%,
      Biotene Oral Balance, 0.0%, Rain, 0.0%, CTx2 Spray, 0.0%, tap water 0.0%, and
      citric acid 18.8%. There was a significant negative correlation between the pH
      values and the erosive potential (r(s) = -0.73; P <= 0.0001). CONCLUSIONS: There
      is large variation in the composition and pH values of commonly used oral
      moisturizers, and there is a strong correlation between pH values and erosive
      potential of commonly used oral moisturizers. CLINICAL SIGNIFICANCE: Patients
      with dry mouth are at increased risk for erosion and root caries. Oral
      moisturizing agents are often prescribed for patients with hyposalivation to be
      used as needed for symptomatic relief. This study shows that there is large
      variation in the pH values and erosive potential of commonly used oral
      moisturizing agents.

PMID- 26216577
TI  - Developmental and evolutionary novelty in the serrated teeth of theropod
      dinosaurs.
AB  - Tooth morphology and development can provide valuable insights into the feeding
      behaviour and evolution of extinct organisms. The teeth of Theropoda, the only
      clade of predominantly predatory dinosaurs, are characterized by ziphodonty, the
      presence of serrations (denticles) on their cutting edges. Known today only in
      varanid lizards, ziphodonty is much more pervasive in the fossil record. Here we
      present the first model for the development of ziphodont teeth in theropods
      through histological, SEM, and SR-FTIR analyses, revealing that structures
      previously hypothesized to prevent tooth breakage instead first evolved to shape
      and maintain the characteristic denticles through the life of the tooth. We show
      that this novel complex of dental morphology and tissues characterizes Theropoda,
      with the exception of species with modified feeding behaviours, suggesting that
      these characters are important for facilitating the hypercarnivorous diet of most
      theropods. This adaptation may have played an important role in the initial
      radiation and subsequent success of theropods as terrestrial apex predators. 

PMID- 26216578
TI  - Identification and management of tardive dyskinesia: A case series and literature
      review.
AB  - Tardive dyskinesia (TD) is a serious, disabling and potentially permanent,
      neurological hyperkinetic movement disorder that occurs after months or years of
      taking dopamine receptor-blocking agents. The pathophysiology of TD is complex,
      multifactorial and still not fully understood. Although there is no identified
      effective and standard treatment for TD, several agents have been tried for the
      management of this motor disturbance. The aim of this case series is to review
      the literature in regard to the identification, diagnosis and the treatment of TD
      with anticholinergics, anticholinergic medication withdrawal, cholinergic agents,
      botulinum toxin intramuscular injections, tetrabenazine, levetiracetam,
      propranolol and zolpidem, and to describe one case of TD that responded favorably
      to clonazepam and two cases of TD that responded favorably to Ginkgo biloba. 

PMID- 26216580
TI  - Unique Case of Imperforate Hymen.
AB  - BACKGROUND: Imperforate hymen typically presents in adolescence with pain,
      hematocolpometra and primary amenorrhea. This case documents a previously
      unreported etiology for an atypical presentation with a history of recent
      menstruation. CASE: A female adolescent presented with symptoms of urinary
      retention and leg pain. She reported a history of irregular, painful menses.
      Clinical examination revealed a pelvic mass and imperforate hymen. Sonography was
      consistent with hematocolpometra. Before a planned hymenectomy, the patient began
      to pass dark blood through a fistulous opening in her vulva. Hymenectomy resulted
      in complete resolution of the pain and hematocolpometra. SUMMARY AND CONCLUSION:
      Identification of the fistulous tract explained the patient's history of
      menstrual bleeding despite an imperforate hymen. Spontaneous rupture of
      hematocolpometra through a fistulous tract to the vulva is a previously
      unreported atypical presentation of imperforate hymen in a "menstruating"
      adolescent with pain and a pelvic mass.

PMID- 26216581
TI  - Multiple pathways of cross-resistance to glycopeptides and daptomycin in
      persistent MRSA bacteraemia.
AB  - BACKGROUND: The development of non-susceptibility to glycopeptides and daptomycin
      in MRSA during persistent bacteraemia has become a significant therapeutic
      challenge. However, the in vivo evolution and mechanism of the dual resistance
      have remained incompletely understood. METHODS: A series of MRSA blood isolates
      with incremental non-susceptibility to glycopeptides and daptomycin were
      consecutively recovered from a bacteraemic patient who was failing chemotherapy.
      The evolutionary pathways during conversion from a glycopeptide- and daptomycin
      susceptible phenotype into a vancomycin-intermediate Staphylococcus aureus (VISA)
      and a daptomycin-resistant S. aureus (DRSA) phenotype were then traced by WGS of
      the isogenic strains. RESULTS: A total of six non-synonymous mutations and three
      evolutionary pathways were identified during the development of the VISA/DRSA
      phenotype. The first pathway involved two steps of evolution, with an initial 1
      bp insertion into yycH and a subsequent gain-in-function point mutation in mprF
      (S295L). The two mutations were correlated with heteroresistance to
      daptomycin/vancomycin and full development of the VISA/DRSA phenotype. The second
      pathway involved an 11 bp deletion mutation in yycH and point mutations at two
      genes, correlating with the development of the VISA phenotype and
      heteroresistance to daptomycin. Mutation in mprF (S295L) and a 5 bp deletion
      mutation in yycH were identified in the third pathway and corresponded to
      conversion into the full VISA/DRSA phenotype. The mutations in yycH resulted in
      premature terminations of YycH with variable lengths. CONCLUSIONS: Multiple
      evolutionary pathways involving yycH and mprF can proceed simultaneously and may
      mediate cross-resistance to glycopeptides and daptomycin during persistent MRSA
      bacteraemia under antibiotic selective pressure.

PMID- 26216579
TI  - Comparison of laparoscopic versus open gastrectomy for advanced gastric cancer:
      an updated meta-analysis.
AB  - BACKGROUND: Laparoscopic gastrectomy (LG) has been used as an alternative to open
      gastrectomy (OG) to treat early gastric cancer. However, the use of LG for
      advanced gastric cancer (AGC) has been in debate. METHODS: Literature retrieval
      was performed by searching PubMed, EMBASE, and the Cochrane library up to July
      2014. Potential studies comparing the surgical effects between LG with OG were
      evaluated and data were extracted accordingly. Meta-analysis was carried out
      using RevMan. The pooled risk ratio and weighted mean difference (WMD) with 95 %
      confidence interval (95 % CI) were calculated. RESULTS: Overall, 26 studies were
      included in this meta-analysis. LG had some advantages over OG, including shorter
      hospitalization (WMD, -3.63, 95 % CI, -4.66 to -2.60; P < 0.01), less blood loss
      (WMD, -161.37, 95 % CI, -192.55 to -130.18; P < 0.01), faster bowel recovery
      (WMD, -0.78, 95 % CI, -1.05 to -0.50; P < 0.01), and earlier ambulation (WMD, 
      0.95, 95 % CI, -1.47 to -0.44; P < 0.01). In terms of surgical and oncological
      safety, LG could achieve similar lymph nodes (WMD, -0.49, 95 % CI, -1.78 to 0.81;
      P = 0.46), a lower complication rate [odds ratio (OR), 0.71, 95 % CI, 0.59 to
      0.87; P < 0.01], and overall survival (OS) and disease-free survival (DFS)
      comparable to OG. CONCLUSIONS: For AGCs, LG appeared comparable with OG in short-
      and long-term results. Although more time was needed to perform LG, it had some
      advantages over OG in achieving faster postoperative recovery. Ongoing trials and
      future studies could help to clarify this controversial issue.

PMID- 26216582
TI  - Prevalence of MRSA and Gram-negative bacteria with ESBLs and carbapenemases in
      patients from Northern Africa at a German hospital.

PMID- 26216583
TI  - Assessing the burden of childhood asthma: validation of electronic versions of
      the Mini Pediatric and Pediatric Asthma Caregiver's Quality of Life
      Questionnaires.
AB  - PURPOSE: To validate electronic versions of the Mini Pediatric and Pediatric
      Asthma Caregiver's Quality of Life Questionnaires (MiniPAQLQ and PACQLQ,
      respectively), determine completion times and correlate QOL of children and
      caregivers. METHODS: A total of 63 children and 64 caregivers completed the paper
      and electronic MiniPAQLQ or PACQLQ. Agreement between versions of each
      questionnaire was summarized by intraclass correlation coefficients (ICC). The
      correlation between MiniPAQLQ and PACQLQ scores from child-caregiver pairs was
      assessed using Pearson's correlation coefficient. RESULTS: There was no
      significant difference (mean difference = 0.1, 95% CI -0.1, 0.2) in MiniPAQLQ
      Overall Scores between paper (5.9 +/- 1.0, mean +/- SD) and electronic (5.8 +/-
      1.0) versions, or any of the domains. ICCs ranged from 0.89 (Overall) to 0.86
      (Emotional Function). Overall PACQLQ scores for both versions were comparable
      (5.9 +/- 0.9 and 5.8 +/- 1.0; mean difference = 0.0; 95% CI -0.1, 0.2). ICCs
      ranged from 0.81 (Activity Limitation) to 0.88 (Emotional Function). The
      electronic PACQLQ took 26 s longer (95% CI 11, 41; p < 0.001). Few participants
      (3-11%) preferred the paper format. MiniPAQLQ and PACQLQ scores were
      significantly correlated (all p < 0.05) for Overall (r paper = 0.33, r electronic
      = 0.27) and Emotional Function domains (r paper = 0.34, r electronic = 0.29).
      CONCLUSIONS: These electronic QOL questionnaires are valid, and asthma-related
      QOL of children and caregivers is related.

PMID- 26216584
TI  - How dead is dead? Qualitative findings from participants of combined traditional
      and lead-time time trade-off valuations.
AB  - PURPOSE: The EuroQol Valuation Technology (EQ-VT) uses traditional time trade-off
      (tTTO) for health states better than dead and lead-time TTO (LT-TTO) for states
      worse than dead to elicit a value (-1.0 to +1.0) for each health state. In the
      Canadian EQ-5D-5L Valuation study which used the EQVT platform, we observed an
      unexpected peak in frequency of "0" values and few negative values, particularly
      in the range of 0 to -0.5. To better understand this finding, we sought to
      explore respondents' thought processes while valuing a health state, and their
      understanding of the tTTO and LT-TTO exercises. METHODS: Qualitative semi
      structured interviews were conducted with EQVT task respondents. Questions
      focused on valuations of health states as: (a) Same as dead in tTTO, (b) Worse
      than dead in tTTO but changed to same as dead in LT-TTO, (c) Worse than dead in
      LT-TTO, and (d) Worse than dead in LT-TTO with trading off all 10 years. Data
      were analyzed using content and thematic analysis. RESULTS: Mean age of
      participants (N = 70) was 40 +/- 18.1 years, 60% female, and 76% Caucasian.
      Participants provided similar reasons for valuing a health state same as or worse
      than dead. Many participants expressed confusion about worse than dead
      valuations, distinction between same as and worse than dead, and the transition
      from tTTO to LT-TTO. A few indicated that the addition of 10 years of full health
      in the LT-TTO influenced their valuations. CONCLUSIONS: The transition from tTTO
      to LT-TTO in the EQVT was confusing to participants, whereby some health state
      valuations around this transition appeared to be arbitrary.

PMID- 26216585
TI  - Quality of life in women with lipoedema: a contextual behavioral approach.
AB  - PURPOSE: Lipoedema is a chronic, progressive adipose disorder of unknown
      etiology, often underdiagnosed or misdiagnosed as obesity. It manifests itself
      with accumulation of the fat in lower parts of the body and associated edema and,
      due to numerous physical and psychological consequences, affects the quality of
      life (QOL) of those who suffer. The aim of this study was to investigate the
      psychological factors that might have an impact on the QOL of women with
      lipoedema from the contextual behavioral viewpoint. METHODS: In an Internet-based
      cross-sectional study, women suffering from lipoedema (N = 120) were asked to
      fill in questionnaires assessing: symptom severity, QOL (WHOQOL-BREF),
      satisfaction with life (SWLS), psychological flexibility (Acceptance and Action
      Questionnaire-II), social connectedness (Social Connectedness Scale-Revised) and
      other psychological factors. The majority of participants were from the USA, the
      UK, and Australia. RESULTS: Multiple hierarchical regression analyses showed that
      a higher level of QOL was predicted by higher levels of psychological flexibility
      and social connectedness, while controlling for symptom severity. Higher level of
      SWL was predicted only by higher level of social connectedness. CONCLUSIONS:
      Acceptance and Commitment Therapy with psychological flexibility as the target of
      change and Functional Analytic Psychotherapy with social connectedness as the
      target of change might be useful in treating women with lipoedema; however,
      further research in this area is needed. The authors conclude that psychological
      and biomedical interventions for women with lipoedema and their QOL merit more
      attention from researchers and the medical community than is currently received.

PMID- 26216586
TI  - Adaptation of the 10-Item Functional Outcomes of Sleep Questionnaire to Iranian
      Patients with Obstructive Sleep Apnea.
AB  - PURPOSE: The purpose of this study was to evaluate the psychometric properties of
      the Farsi version of 10-item Functional Outcomes of Sleep Questionnaire (FOSQ-10)
      in Iranian patients with obstructive sleep apnea (OSA). METHODS: The FOSQ-10 was
      translated into Farsi using the standard forward-backward method. One hundred
      patients who fulfilled the inclusion criteria completed a series of
      questionnaires including IR-FOSQ-10, Medical Outcome Survey Short Form 12 (SF-12)
      and Epworth Sleepiness Scale (ESS). Internal consistency, test-retest
      reliability, concurrent validity, discriminant validity and responsiveness of IR
      FOSQ-10 were investigated. RESULTS: The Cronbach's alpha coefficient was 0.85 in
      IR-FOSQ-10 total score and ranged from 0.78 to 0.83 in each subscale. The test
      retest reliability demonstrated by intraclass coefficient was 0.92. There were
      significant moderate-to-good negative correlations between IR-FOSQ-10 subscales
      and ESS except for sexual relationship subscale. FOSQ-10 subscales generally
      correlated higher with related subscales of SF-12. The IR-FOSQ-10 was able to
      distinguish patients with abnormal sleepiness score from those with normal
      sleepiness score. The results of sensitivity to change proved that the IR-FOSQ-10
      was able to detect changes after continuous positive airway pressure therapy.
      CONCLUSION: The psychometric properties of the IR-FOSQ-10 suggest that it is a
      reliable and valid measure among Iranian patients with OSA.

PMID- 26216587
TI  - Hepatitis E virus genotype 4 in Southeastern France: still around.

PMID- 26216588
TI  - Impact of age on the feasibility and efficacy of neoadjuvant chemotherapy in
      patients with locally advanced oesophagogastric cancer.
AB  - INTRODUCTION: Neoadjuvant chemotherapy (neoCTx) improves the prognosis of
      patients with localised oesophagogastric adenocarcinoma (EGC), but its value is
      unknown in elderly patients. PATIENTS AND METHODS: Patients who received neoCTx
      followed by surgery for EGC between 2000 and 2012 were analysed. The aim of this
      study was to compare the feasibility and outcome between patients aged ?70
      (cohort I) and their younger counterparts (cohort II). RESULTS: Data were
      available for 460 patients among which 174 (38%) were ?70 years. Older age was
      associated with an increased rate of comorbidities (66% versus 42%, p<0,001). As
      compared to the younger, elderly patients were more likely to receive doublet
      instead of triplet neoCTx (65% versus 37%, p<0.001) and oxaliplatin-instead of
      cisplatin-based regimens (60% versus 32%, p<0.001). No significant difference was
      observed in the rate of ?grade 3 toxicities for cohort I and II (48% versus 41%)
      and postoperative morbidity was also not different (24% versus 28%). 90 day
      mortality for cohort I and II was 6.5% and 3.9%. After a median follow-up of 38
      months, median disease-free survival (DFS) was 29.4 months in cohort I and 33.8
      months in cohort II, with a 5-years DFS of 37% and 40%, respectively. Median
      overall survival (OS) was not reached in cohort I and was 58.4 months in cohort
      II, with a 5-year OS of 51% and 50% for cohort I and II, respectively.
      DISCUSSION: Despite slightly more adverse events and dose reductions, neoCTx is
      feasible in elderly patients with EGC. Elderly patients achieve comparable
      survival outcomes compared with their younger counterparts.

PMID- 26216589
TI  - The Effects of Video Games on Cognition and Brain Structure: Potential
      Implications for Neuropsychiatric Disorders.
AB  - Video games are now a ubiquitous form of entertainment that has occasionally
      attracted negative attention. Video games have also been used to test cognitive
      function, as therapeutic interventions for neuropsychiatric disorders, and to
      explore mechanisms of experience-dependent structural brain changes. Here, we
      review current research on video games published from January 2011 to April 2014
      with a focus on studies relating to mental health, cognition, and brain imaging.
      Overall, there is evidence that specific types of video games can alter brain
      structure or improve certain aspects of cognitive functioning. Video games can
      also be useful as neuropsychological assessment tools. While research in this
      area is still at a very early stage, there are interesting results that encourage
      further work in this field, and hold promise for utilizing this technology as a
      powerful therapeutic and experimental tool. 

PMID- 26216590
TI  - Internet Gaming Disorder in the DSM-5.
AB  - The fifth revision of the Diagnostic and Statistical Manual of Mental Disorders
      (DSM-5) includes in its research appendix a potential new diagnosis-Internet
      gaming disorder. This article outlines the debate surrounding non-substance
      addictions and the rationale for including this condition in the "Conditions for
      Further Study" chapter in DSM-5 Section III. It also describes the diagnostic
      criteria that DSM-5 recommends and methods to assess Internet gaming disorder.
      The paper details international research related to prevalence rates,
      demographic, psychiatric, and neurobiological risk factors, the natural course of
      the condition, and promising treatment approaches. The paper concludes by
      describing important issues for research to address prior to official recognition
      of this condition as a mental disorder. 

PMID- 26216591
TI  - Sleep, Circadian Rhythms, and Anxious Traits.
AB  - Anxiety is adaptive and plays an important role in keeping us safe. However, when
      anxiety becomes too extreme, it can cause significant disruptions and distress.
      Understanding the mechanisms underlying excessive anxiety and how to best treat
      it is a priority for researchers and clinicians. There is increasing recognition
      that disruptions in the amount and timing of sleep are associated with anxiety
      symptoms and characteristics. In the current paper, we explore the intersections
      between sleep, circadian rhythms, and anxiety. First, we review accumulating
      evidence that anxiety is associated with disruptions in sleep and circadian
      rhythms in both clinical and nonclinical samples and across ages. Next, we
      discuss the data linking sleep disruptions with anxiety-related traits (anxiety
      sensitivity, neuroticism, and perfectionism) and patterns of cognition and
      emotion. Finally, potential treatment implications are highlighted. Overall,
      these data suggest that delineating the role of disruptions in the amount and
      timing of sleep holds promise for improving the lives of individuals with
      heightened anxiety. 

PMID- 26216592
TI  - Li-Metal-Free Prelithiation of Si-Based Negative Electrodes for Full Li-Ion
      Batteries.
AB  - Most of the high-capacity positive-electrode materials [for example, S, O2 (air),
      and MOx (M: V, Mn, Fe, etc.)] are Li-deficient and require the use of a Li-metal
      electrode or prelithiation. Herein, we report a novel electrolytic cell in which
      the Si electrode can be prelithiated in a well-controlled manner from Li
      containing aqueous solution in a Li-metal-free way. MnOx/Si and S/Si Li-ion full
      cells were assembled by using the prelithiated Si negative electrodes, which
      resulted in high specific energies of 349 and 732 Wh kg(-1), respectively. The
      MnOx/Si full cell still retains 138 Wh kg(-1) even at a high specific power of
      1710 W kg(-1). This is the first report of a whole process of making a full Li
      ion battery with both Li-deficient electrodes without the use of Li metal as the
      Li source. This novel prelithiation process, with high controllability, no short
      circuiting, and an abundant Li source, is expected to contribute significantly to
      the development of safe, green, and powerful Li-ion batteries.

PMID- 26216593
TI  - Australian government ready to deny welfare benefits to anti-vaccine parents.

PMID- 26216594
TI  - The EuPA Biobank Initiative: Meeting the future challenges of   biobanking in
      proteomics   & systems medicine.
AB  - In this News & Reviews Discussion, the recently launched EuPA (European
      Proteomics Association) Biobank Initiative is introduced in the context of
      current and future challenges in biobanking. The purpose of the initiative is to
      provide a forumand knowledge platform for integrating the extensive experiences
      collected by the EuPA community, and link it to the European and international
      biobanking communities at large. The specific impact of providing a forum and
      easy access to this type of information to the EuPA community is the potential of
      improving the quality of future sample collections and biobanks, the quality of
      the research produced from these sample collections, as well as the output and
      productivity from existing biobanks. The underutilization of biobanks has
      recently been identified as an emerging issue of biobankingworldwide. Measures to
      improve our ability to locate and access appropriate sample collections for a
      wide range of research purposes may enhance both the scientific quality and
      biobank sustainability, thereby contributing to the important task of moving our
      research beyond basic findings and mere publications, into clinical practice.
      BIOLOGICAL SIGNIFICANCE: This manuscript is intended as a Discussion piece, and
      represents a recollection of the presentation under the "EuPA Initiative" session
      at HUPO/EuPA 2014 in Madrid. The launch of the EuPA (European Proteomics
      Association) Biobank Initiative in the context of current and future challenges
      in biobanking is discussed. The purpose of the initiative is to provide a forum
      and knowledge base for integrating the extensive experiences collected by the
      EuPA community, and link it to the European and international biobanking
      communities at large. The specific impact of providing a forumand easy access to
      this type of information to the EuPA community is the potential of improving the
      quality of future sample collections and biobanks, the quality of the research
      produced from these sample collections, aswell as the output and productivity
      fromexisting biobanks. The underutilization of biobanks has recently been
      identified as a challenge to the well-being and economic sustainability of
      biobanking worldwide. Measures to improve our ability to localize and access
      appropriate sample collections for validation studies and other research purposes
      is thus of benefit bothto scientific quality and biobank sustainability, thereby
      contributing to the important task of moving our research beyond basic findings
      and mere publications, into clinical practice. This article is part of a Special
      Issue entitled: HUPO 2014.

PMID- 26216595
TI  - Proteomic-driven biomarker discovery in gestational diabetes mellitus: a review.
AB  - Gestational diabetes mellitus (GDM) is defined as any degree of glucose
      intolerance with onset or first recognition during pregnancy and it affects 18%
      of pregnant women worldwide. GDM is considered a high-risk state which may lead
      to type II diabetes which is associated with an increase in a number of
      interrelated adverse perinatal outcomes. Given the fact that the progress of a
      successful pregnancy is dependent on the intricate communication between several
      biological molecules, identification of the proteomic profile perturbations in
      women with GDM is expected to help in understanding the disease pathogenesis and
      also discovery of clinical biomarker(s). In recent years, both gel-free and gel
      based proteomics have been extensively investigated for improving maternal and
      child health. Although there are several reports integrating various aspects of
      proteomics in pregnancy related diseases such as preeclampsia, extensive Pubmed
      search shows no review so far on the application of proteomics in gestational
      diabetes. In this review, we focus on various high-throughput proteomic
      technologies for the identification of unique biosignatures and biomarkers
      responsible for the early prediction of GDM. Further, different analytical
      strategies and biological samples involved in proteomic analysis of this
      pregnancy-related disease are discussed.This article is part of a Special Issue
      entitled: Proteomics in India.

PMID- 26216596
TI  - Computational and statistical methods for high-throughput analysis of post
      translational modifications of proteins.
AB  - The investigation of post-translational modifications (PTMs) represents one of
      the main research focuses for the study of protein function and cell signaling.
      Mass spectrometry instrumentation with increasing sensitivity improved protocols
      for PTM enrichment and recently established pipelines for high-throughput
      experiments allow large-scale identification and quantification of several PTM
      types. This review addresses the concurrently emerging challenges for the
      computational analysis of the resulting data and presents PTM-centered approaches
      for spectra identification, statistical analysis, multivariate analysis and data
      interpretation. We furthermore discuss the potential of future developments that
      will help to gain deep insight into the PTM-ome and its biological role in cells.
      This article is part of a Special Issue entitled: Computational Proteomics. 

PMID- 26216597
TI  - Macrophage development and polarization in chronic inflammation.

PMID- 26216598
TI  - Phosphatase regulation of macrophage activation.
AB  - Macrophages are innate immune cells that play critical roles in tissue
      homeostasis and the immune response to invading pathogens or tumor cells. A
      hallmark of macrophages is their "plasticity," that is, their ability to respond
      to cues in their local microenvironment and adapt their activation state or
      phenotype to mount an appropriate response. During the inflammatory response,
      macrophages may be required to mount a profound anti-bacterial or anti-tumor
      response, an anti-inflammatory response, an anti-parasitic response, or a wound
      healing response. To do so, macrophages express cell surface receptors for growth
      factors, chemokines and cytokines, as well pathogen and danger associated
      molecular patterns. Downstream of these cell surface receptors, cell signalling
      cascades are activated and deactivated by reversible and competing activities of
      lipid and protein kinases and phosphatases. While kinases drive the activation of
      cell signalling pathways critical for macrophage activation, the strength and
      duration of the signalling is regulated by phosphatases. Hence, gene knockout
      mouse models have revealed critical roles for lipid and protein phosphatases in
      macrophage activation. Herein, we describe our current understanding and the key
      roles of specific cellular phosphatases in the regulation of the quality of
      macrophage polarization as well as the quantity of cytokines produced by
      activated macrophages. 

PMID- 26216599
TI  - Translation and psychometric evaluation of a French version of the Readiness for
      Hospital Discharge Scale.
AB  - AIMS AND OBJECTIVES: To evaluate the reliability and the factor structure of the
      Readiness for Hospital Discharge Scale-French version. BACKGROUND: The patient's
      perspective is essential when assessing risk for adverse events at hospital
      discharge. Developed in the USA, the Readiness for Hospital Discharge Scale is
      the only instrument that measures an individual's self-perception of readiness
      before leaving the hospital. A French version of the Readiness for Hospital
      Discharge Scale was developed and validated. DESIGN: Cross-sectional study.
      METHODS: A convenience sample of 265 older inpatients from four medical units was
      selected. The translation and cultural adaptation of the scale involved experts
      in gerontology and the French language and included back translation. The items
      were semantically evaluated and pretested in 10 older inpatients. The scale's
      psychometric properties were internally validated by using confirmatory and
      exploratory factor analyses. Reliability was assessed by examining the internal
      consistency of its items. RESULTS: Goodness-of-fit indices of the confirmatory
      factor analyses were not adequate, but reliability was acceptable (Cronbach's
      alpha = 0.80). Exploratory factor analysis of the French version provided results
      close to those described for the English version, with three similar subscales
      (physical and emotional readiness, coping with medical treatment and personal
      care), whereas the initially described Expected Support subscale was not
      identified in the French version. CONCLUSION: The Readiness for Hospital
      Discharge Scale-French version appears to be partially consistent with its
      original English version, but requires additional adaptation to fully take into
      account the Swiss context and culture to achieve its original aim. RELEVANCE TO
      CLINICAL PRACTICE: Assessing patient readiness for hospital discharge before
      leaving hospital could help nurses to improve the discharge planning process and
      achieve better patient preparedness and care coordination.

PMID- 26216601
TI  - Relieving oxidative stress in immune cells.

PMID- 26216600
TI  - Variation in Association Between Thiazolidinediones and Heart Failure Across
      Ethnic Groups: Retrospective analysis of Large Healthcare Claims Databases in Six
      Countries.
AB  - INTRODUCTION: The prevalence of polymorphisms among the metabolising enzymes and
      pharmacodynamic receptors relevant for the thiazolidinediones differs by ethnic
      group, a factor that may modify risk of adverse drug events. OBJECTIVE: The aim
      of the study was to determine if the risk of oedema or heart failure associated
      with the thiazolidinediones varies in populations in Australia, Canada, Hong
      Kong, Japan, Korea and Taiwan. METHODS: Sequence symmetry analyses were
      undertaken to investigate the risk of peripheral oedema, as measured by incident
      furosemide dispensing, and risk of hospitalisations for heart failure. Results
      were pooled, with Australia and Canada representing predominantly Caucasian
      population and all other countries contributing to Asian population estimates.
      RESULTS: Pooled estimates of risk for furosemide initiation in the Caucasian
      populations were significantly increased for pioglitazone [adjusted sequence
      ratio (ASR) 1.47; 95 % confidence interval (CI) 1.14-1.91] and rosiglitazone (ASR
      1.65; 95 % CI 1.58-1.72), while in the Asian populations, the pooled risk
      estimates were lower (ASR 1.11; 95 % CI 0.93-1.32 and ASR 1.21; 95 % CI 1.01-1.45
      for pioglitazone and rosiglitazone, respectively). Results for hospitalisation
      for heart failure showed a similar trend, with elevated risk in the Australian
      data (ASR 1.88; 95 % CI 1.01-3.5 and ASR 1.25; 95 % CI 0.76-2.05 for pioglitazone
      and rosiglitazone, respectively), while no increased risk was found in the pooled
      results for the Asian populations. CONCLUSION: The risk of both oedema and heart
      failure with thiazolidinediones was higher in predominantly Caucasian countries
      than in the Asian countries assessed. Assessment of adverse events by ethnicity
      may support safer medicine use.

PMID- 26216602
TI  - Saving beta cell function in the NIK of time.

PMID- 26216603
TI  - Immune-mediated viral clearance from the CNS without collateral damage.

PMID- 26216604
TI  - Resolvins on the way to resolution.

PMID- 26216605
TI  - Self-targeting blocks malaria parasite invasion.

PMID- 26216606
TI  - Effects of thermophilic composting on oxytetracycline, sulfamethazine, and their
      corresponding resistance genes in swine manure.
AB  - Environmental contamination caused by residual antibiotics and antibiotic
      resistance genes (ARGs) in concentrated animal feeding operations has drawn
      increasing attention. This study investigated the removal of oxytetracycline
      (OTC) and sulfamethazine (SMN) as well as the behavior of their corresponding
      ARGs through a series of simulated composting tests with swine manure. The
      results indicate that the composting piles became fully mature after 32 days when
      the thermophilic stage was maintained at 55  degrees C for 3.5 days. At an
      initial spiked concentration of 50 (SMN) and 32 mg kg(-1) (OTC), their removal
      efficiency could reach 89.8% and 100%, respectively. An abiotic process was
      mainly responsible for the degradation of SMN, whereas both abiotic and biotic
      processes were responsible for the degradation of OTC. Among all the studied
      ARGs, only the tetracycline resistance genes (TRGs) encoding ribosomal protection
      proteins remained relatively stable throughout the composting process, while
      those encoding efflux pump (EFP) and enzymatic inactivation (EI) proteins and
      sulfonamide resistance genes (SRGs) obviously increased when the composting was
      complete. The addition of antibiotics inhibited the microbial activity in the
      early stage of composting but promoted the proliferation of ARGs particularly in
      the mesophilic stage. Integron-mediated horizontal gene transfers played an
      important role in the proliferation of most ARG types studied (i.e., EFP TRGs, EI
      TRG and SRGs). In summary, thermophilic composting of swine manure could remove
      the studied antibiotics effectively, but failed to prevent the proliferation of
      their corresponding ARGs. 

PMID- 26216607
TI  - A rare cause of status epilepticus; alpha lipoic acid intoxication, case report
      and review of the literature.
AB  - INTRODUCTION: Alpha lipoic acid is a powerful antioxidant widely used for the
      supplementary treatment of diabetic neuropathy. Intoxication with alpha lipoic
      acid is very rare. There is no reported dose of safety in children. CASE REPORT:
      A 14-month-old previously healthy girl was referred to our hospital with the
      diagnosis of drug intoxication. She was admitted to the emergency department with
      lethargy and continuing involuntary movements for several hours after she had
      ingested an unknown amount of alpha lipoic acid. On admission she was lethargic
      and had myoclonic seizures involving all extremities. She had no fever and
      laboratory examinations were normal except for mild metabolic acidosis. The
      seizures were unresponsive to bolus midazolam, phenytoin infusion and
      levetiracetam infusion. She was taken to the pediatric intensive care unit with
      the diagnosis of status epilepticus. After failure of the treatment with
      midazolam infusion she was intubated and thiopental sodium infusion was started.
      Her myoclonic seizures were controlled with thiopental sodium infusion. After 48
      h intubation and mechanical ventilation thiopental sodium was gradually reduced
      and then stopped. Following the withdraw of thiopental sodium, she was seizure
      free on her discharge on the 8th day. CONCLUSION: Alpha lipoic acid and
      derivatives cause side effects in children like refractory convulsions. They are
      frequently rendered as vitamins by diabetic patients and are left at places where
      children can easily access them. Therefore, when faced with refractory
      convulsions in children who have had no disease before, intoxication by
      medicaments with alpha lipoic acid should be taken into consideration.

PMID- 26216609
TI  - What happened to you?

PMID- 26216608
TI  - Effect of nasal balloon autoinflation in children with otitis media with effusion
      in primary care: an open randomized controlled trial.
AB  - BACKGROUND: Otitis media with effusion is a common problem that lacks an evidence
      based nonsurgical treatment option. We assessed the clinical effectiveness of
      treatment with a nasal balloon device in a primary care setting. METHODS: We
      conducted an open, pragmatic randomized controlled trial set in 43 family
      practices in the United Kingdom. Children aged 4-11 years with a recent history
      of ear symptoms and otitis media with effusion in 1 or both ears, confirmed by
      tympanometry, were allocated to receive either autoinflation 3 times daily for 1
      3 months plus usual care or usual care alone. Clearance of middle-ear fluid at 1
      and 3 months was assessed by experts masked to allocation. RESULTS: Of 320
      children enrolled, those receiving autoinflation were more likely than controls
      to have normal tympanograms at 1 month (47.3% [62/131] v. 35.6% [47/132];
      adjusted relative risk [RR] 1.36, 95% confidence interval [CI] 0.99 to 1.88) and
      at 3 months (49.6% [62/125] v. 38.3% [46/120]; adjusted RR 1.37, 95% CI 1.03 to
      1.83; number needed to treat = 9). Autoinflation produced greater improvements in
      ear-related quality of life (adjusted between-group difference in change from
      baseline in OMQ-14 [an ear-related measure of quality of life] score -0.42, 95%
      CI -0.63 to -0.22). Compliance was 89% at 1 month and 80% at 3 months. Adverse
      events were mild, infrequent and comparable between groups. INTERPRETATION:
      Autoinflation in children aged 4-11 years with otitis media with effusion is
      feasible in primary care and effective both in clearing effusions and improving
      symptoms and ear-related child and parent quality of life. TRIAL REGISTRATION:
      ISRCTN, No. 55208702.

PMID- 26216610
TI  - Autoinflation: an effective nondrug intervention for glue ear.

PMID- 26216611
TI  - Non-obstetric diagnostic imaging in pregnancy.

PMID- 26216612
TI  - Panel recommends health care innovation fund to be administered by new agency.

PMID- 26216613
TI  - Need to define patient engagement in research.

PMID- 26216614
TI  - Synchrotron sheds new light on research questions.

PMID- 26216615
TI  - The costs of vilifying pharma.

PMID- 26216616
TI  - H1N1 vaccine and narcolepsy link discovered.

PMID- 26216617
TI  - The direct cost of epilepsy in the United States: A systematic review of
      estimates.
AB  - OBJECTIVE: To develop estimates of the direct cost of epilepsy in the United
      States for the general epilepsy population and sub-populations by systematically
      comparing similarities and differences in types of estimates and estimation
      methods from recently published studies. METHODS: Papers published since 1995
      were identified by systematic literature search. Information on types of
      estimates, study designs, data sources, types of epilepsy, and estimation methods
      was extracted from each study. Annual per person cost estimates from
      methodologically similar studies were identified, converted to 2013 U.S. dollars,
      and compared. RESULTS: From 4,104 publications discovered in the literature
      search, 21 were selected for review. Three were added that were published after
      the search. Eighteen were identified that reported estimates of average annual
      direct costs for the general epilepsy population in the United States. For
      general epilepsy populations (comprising all clinically defined subgroups), total
      direct healthcare costs per person ranged from $10,192 to $47,862 and epilepsy
      specific costs ranged from $1,022 to $19,749. Four recent studies using claims
      data from large general populations yielded relatively similar epilepsy-specific
      annual cost estimates ranging from $8,412 to $11,354. Although more difficult to
      compare, studies examining direct cost differences for epilepsy sub-populations
      indicated a consistent pattern of markedly higher costs for those with
      uncontrolled or refractory epilepsy, and for those with comorbidities.
      SIGNIFICANCE: This systematic review found that various approaches have been used
      to estimate the direct costs of epilepsy in the United States. However, recent
      studies using large claims databases and similar methods allow estimation of the
      direct cost burden of epilepsy for the general disease population, and show that
      it is greater for some patient subgroups. Additional research is needed to
      further understand the broader economic burden of epilepsy and how it varies
      across subpopulations.

PMID- 26216618
TI  - Challenges in replicating brain-behavior correlations: Rejoinder to Kanai (2015)
      and Muhlert and Ridgway (2015).

PMID- 26216619
TI  - Observation of non-Markovian micromechanical Brownian motion.
AB  - All physical systems are to some extent open and interacting with their
      environment. This insight, basic as it may seem, gives rise to the necessity of
      protecting quantum systems from decoherence in quantum technologies and is at the
      heart of the emergence of classical properties in quantum physics. The precise
      decoherence mechanisms, however, are often unknown for a given system. In this
      work, we make use of an opto-mechanical resonator to obtain key information about
      spectral densities of its condensed-matter heat bath. In sharp contrast to what
      is commonly assumed in high-temperature quantum Brownian motion describing the
      dynamics of the mechanical degree of freedom, based on a statistical analysis of
      the emitted light, it is shown that this spectral density is highly non-Ohmic,
      reflected by non-Markovian dynamics, which we quantify. We conclude by
      elaborating on further applications of opto-mechanical systems in open system
      identification. 

PMID- 26216620
TI  - Facile Synthesis of Core-shell Magnetic Mesoporous Silica Nanoparticles for pH
      sensitive Anticancer Drug Delivery.
AB  - The facile synthesis of core-shell magnetic mesoporous silica nanoparticles (Fe3
      O4 @mSiO2 NPs) was reported in aqueous phase using cetyltrimethylammonium bromide
      as a template under alcohol-free conditions. Compared to the conventional
      synthesis method for core-shell Fe3 O4 @mSiO2 NPs, the approach in this study is
      rapid (only 5-min reaction time), cheap (without using organic agents), and
      environmentally friendly (one-step synthesis in alcohol-free medium). Doxorubicin
      (DOX)-loaded Fe3 O4 @mSiO2 NPs exert extraordinarily high specificity for liver
      cancer cells, which was due to the pH-sensitive doxorubicin release, as well as
      higher endocytosis capacity in liver cancer cells rather than normal liver cells.
      The potential advantages of using such Fe3 O4 @mSiO2 NPs as the vehicle of
      anticancer drugs were that the Fe3 O4 @mSiO2 NPs exhibit good biocompatibility,
      high loading and protection of the guest molecules, selective killing effect, and
      efficient cellular uptake. The exciting pH-dependent release properties of
      doxorubicin-loaded Fe3 O4 @mSiO2 NPs make their use a promising strategy for
      enhancing efficient therapy toward tumors, while reducing the cytotoxicity of
      doxorubicin to human normal neutral tissue or cells. 

PMID- 26216621
TI  - Iridium-catalyzed asymmetric cyclization of alkenoic acids leading to gamma
      lactones.
AB  - Asymmetric cyclization of alkenoic acids was realized by the use of an
      iridium/chiral bisphosphine catalyst, giving high yields of the corresponding
      gamma-lactones with good enantioselectivity. 

PMID- 26216622
TI  - Device therapy: Saving lives with appropriate ICD therapy in elderly patients.

PMID- 26216623
TI  - Anticoagulation therapy: Benefits of extended oral anticoagulation after first
      episode of pulmonary embolism.

PMID- 26216624
TI  - Systematic review with meta-analysis: Saccharomyces boulardii in the prevention
      of antibiotic-associated diarrhoea.
AB  - BACKGROUND: Antibiotic-associated diarrhoea is a common complication of
      antibiotic use, but it can be prevented with administration of probiotics. AIM:
      To update our 2005 meta-analysis on the effectiveness of Saccharomyces boulardii
      in preventing antibiotic-associated diarrhoea in children and adults. METHODS:
      The Cochrane Library, MEDLINE, and EMBASE databases were searched up until May
      2015, with no language restrictions, for randomised controlled trials; additional
      references were obtained from reviewed articles. The quality of evidence was
      assessed using the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) guidelines. RESULTS: Twenty-one randomised controlled trials
      (4780 participants), among which 16 were new trials, met the inclusion criteria
      for this updated systematic review. Administration of S. boulardii compared with
      placebo or no treatment reduced the risk of antibiotic-associated diarrhoea (as
      defined by the study investigators) in patients treated with antibiotics from
      18.7% to 8.5% (risk ratio, RR: 0.47; 95% CI: 0.38-0.57, number needed to treat,
      NNT: 10; 95% CI: 9-13). In children, S. boulardii reduced the risk from 20.9% to
      8.8% (6 randomised controlled trials, n=1653, RR: 0.43, 95% CI: 0.3-0.6); in
      adults, from 17.4% to 8.2% (15 randomised controlled trials, n=3114, RR: 0.49,
      95% CI: 0.38-0.63). Moreover, S. boulardii reduced the risk of Clostridium
      difficile-associated diarrhoea; however, this reduction was significant only in
      children (2 randomised controlled trials, n = 579, RR: 0.25; 95% CI: 0.08-0.73)
      and not in adults (9 randomised controlled trials, n = 1441, RR: 0.8, 95% CI:
      0.47-1.34). CONCLUSIONS: This meta-analysis confirms that S. boulardii is
      effective in reducing the risk of antibiotic-associated diarrhoea in children and
      adults.

PMID- 26216625
TI  - Trends in the 15D health-related quality of life over the first year following
      diagnosis of head and neck cancer.
AB  - Management of head and neck cancer influences both physical and mental wellbeing.
      Measuring the health-related quality of life (HRQoL) is important, as various
      treatment modalities are associated with significant morbidity and mortality. In
      this prospective cohort study, we tested the feasibility of the generic 15D HRQoL
      instrument in 214 head and neck cancer patients managed with surgery, definitive
      (chemo)radiotherapy, or with combined modality treatment. HRQoL was assessed at
      baseline and three times after treatment onset during 1 year, and compared with
      that of general population standardized for age and sex. At baseline, the
      patients' mean 15D score was significantly worse compared with general
      population. Overall HRQoL was at lowest at 3 months after treatment onset, it
      gradually improved towards 12 months but never reached baseline levels. The
      dimensions "vitality", "distress", "depression" and "sexual activity" showed
      marked deterioration at 3 months after the treatment onset, but improved
      gradually during 12 months. The 15D instrument seems useful for evaluation of
      HRQoL of head and neck cancer patients. Dimensions reflecting mental wellbeing
      improved gradually after 3 months, but they seldom reached baseline levels. The
      support for patients at the time of diagnosis, during treatment, and recovery is
      emphasized. 

PMID- 26216626
TI  - Synthesis of Nature-Inspired Medium-Sized Fused Heterocycles from Amino Acids.
AB  - Herein, we describe the synthesis of molecular scaffolds consisting of medium
      sized fused heterocycles using amino acids, which are some of the most useful
      building blocks used by nature as well as chemists to create structural
      diversity. The acyclic precursors were assembled by using traditional Merrifield
      solid-phase peptide synthesis, and cyclization was carried out through acid
      mediated tandem endocyclic N-acyliminium ion formation, followed by nucleophilic
      addition with internal nucleophiles. The synthesis of molecular scaffolds
      consisting of seven-, eight-, and nine-membered rings proceeded with full
      stereocontrol of the newly generated stereogenic center in most cases. 

PMID- 26216627
TI  - Toward Standardized Musculoskeletal Ultrasound in Pediatric Rheumatology: Normal
      Age-Related Ultrasound Findings.
AB  - OBJECTIVE: The Outcome Measures in Rheumatology Ultrasound Task Force has
      recently started to work on the validation and standardization of musculoskeletal
      ultrasound (MSUS) examination in children in order to improve its applicability
      to joint examination. METHODS: This was a prospective multicenter study performed
      by 4 experts in pediatric MSUS, who independently collected representative images
      using predefined scanning procedures of 4 joints (knee, ankle, wrist, and second
      metacarpophalangeal joint) in different predefined age groups. Researchers were
      allowed to use their own settings (B-mode and Doppler) in order to get the best
      quality image and highest sensitivity for low blood flow. Images were evaluated
      for quality parameters and an atlas was created with the best images. An
      equipment comparative study was performed by a single examiner using 2 different
      types of machines. RESULTS: Sixty-four healthy children were scanned. The quality
      of evaluated images, obtained by predefined scanning positions, was highly
      comparable among the examiners. The B-mode images clearly showed age-related
      variations of joint findings, while Doppler images showed the presence of blood
      flow, particularly within the epiphyseal cartilage of the children at a younger
      age. There was a high to good level of consistency between images obtained from
      the 2 different ultrasound machines. CONCLUSION: The study shows a systematic
      method for ultrasound examination of children at different age groups.
      Additionally, a baseline collection of images was developed, showing blood
      vessels in the joints examined. The present study could provide a framework for
      ongoing MSUS studies as well as for clinical practice in pediatric rheumatology.

PMID- 26216628
TI  - The Hide-and-Seek of Grain Boundaries from Moire Pattern Fringe of Two
      Dimensional Graphene.
AB  - Grain boundaries (GBs) commonly exist in crystalline materials and affect various
      properties of materials. The facile identification of GBs is one of the
      significant requirements for systematical study of polycrystalline materials
      including recently emerging two-dimensional materials. Previous observations of
      GBs have been performed by various tools including high resolution transmission
      electron microscopy. However, a method to easily identify GBs, especially in the
      case of low-angle GBs, has not yet been well established. In this paper, we
      choose graphene bilayers with a GB as a model system and investigate the effects
      of interlayer rotations to the identification of GBs. We provide a critical
      condition between adjacent moire fringe spacings, which determines the
      possibility of GB recognition. In addition, for monolayer graphene with a grain
      boundary, we demonstrate that low-angle GBs can be distinguished easily by
      inducing moire patterns deliberately with an artificial reference overlay. 

PMID- 26216629
TI  - The New Era of Cancer Immunotherapy: Manipulating T-Cell Activity to Overcome
      Malignancy.
AB  - Using the immune system to control cancer has been investigated for over a
      century. Yet it is only over the last several years that therapeutic agents
      acting directly on the immune system have demonstrated improved overall survival
      for cancer patients in phase III clinical trials. Furthermore, it appears that
      some patients treated with such agents have been cured of metastatic cancer. This
      has led to increased interest and acceleration in the rate of progress in cancer
      immunotherapy. Most of the current immunotherapeutic success in cancer treatment
      is based on the use of immune-modulating antibodies targeting critical
      checkpoints (CTLA-4 and PD-1/PD-L1). Several other immune-modulating molecules
      targeting inhibitory or stimulatory pathways are being developed. The combined
      use of these medicines is the subject of intense investigation and holds
      important promise. Combination regimens include those that incorporate targeted
      therapies that act on growth signaling pathways, as well as standard chemotherapy
      and radiation therapy. In fact, these standard therapies have intrinsic immune
      modulating properties that can support antitumor immunity. In the years ahead,
      adoptive T-cell therapy will also be an important part of treatment for some
      cancer patients. Other areas which are regaining interest are the use of
      oncolytic viruses that immunize patients against their own tumors and the use of
      vaccines against tumor antigens. Immunotherapy has demonstrated unprecedented
      durability in controlling multiple types of cancer and we expect its use to
      continue expanding rapidly.

PMID- 26216630
TI  - Immune Targeting of Tumor Epithelial-Mesenchymal Transition via Brachyury-Based
      Vaccines.
AB  - As a manifestation of their inherent plasticity, carcinoma cells undergo profound
      phenotypic changes during progression toward metastasis. One such phenotypic
      modulation is the epithelial-mesenchymal transition (EMT), an embryonically
      relevant process that can be reinstated by tumor cells, resulting in the
      acquisition of metastatic propensity, stem-like cell properties, and resistance
      to a variety of anticancer therapies, including chemotherapy, radiation, and some
      small-molecule targeted therapies. Targeting of the EMT is emerging as a novel
      intervention against tumor progression. This review focuses on the potential use
      of cancer vaccine strategies targeting tumor cells that exhibit mesenchymal-like
      features, with an emphasis on the current status of development of vaccine
      platforms directed against the T-box transcription factor brachyury, a novel
      cancer target involved in tumor EMT, stemness, and resistance to therapies. Also
      presented is a summary of potential mechanisms of resistance to immune-mediated
      attack driven by EMT and the development of novel combinatorial strategies based
      on the use of agents that alleviate tumor EMT for an optimized targeting of
      plastic tumor cells that are responsible for tumor recurrence and the
      establishment of therapeutic refractoriness. 

PMID- 26216632
TI  - Phagocytes as Corrupted Policemen in Cancer-Related Inflammation.
AB  - Inflammation is a key component of the tumor microenvironment. Tumor-associated
      macrophages (TAMs) and tumor-associated neutrophils (TANs) are prototypic
      inflammatory cells in cancer-related inflammation. Macrophages provide a first
      line of resistance against infectious agents but in the ecological niche of
      cancer behave as corrupted policemen. TAMs promote tumor growth and metastasis by
      direct interactions with cancer cells, including cancer stem cells, as well as by
      promoting angiogenesis and tissue remodeling and suppressing effective adaptive
      immunity. In addition, the efficacy of chemotherapy, radiotherapy, and checkpoint
      blockade inhibitors is profoundly affected by regulation of TAMs. In particular,
      TAMs can protect and rescue tumor cells from cytotoxic therapy by orchestrating a
      misguided tissue repair response. Following extensive preclinical studies, there
      is now proof of concept that targeting tumor-promoting macrophages by diverse
      strategies (e.g., Trabectedin, anti-colony-stimulating factor-1 receptor
      antibodies) can result in antitumor activity in human cancer and further studies
      are ongoing. Neutrophils have long been overlooked as a minor component of the
      tumor microenvironment, but there is evidence for an important role of TANs in
      tumor progression. Targeting phagocytes (TAMs and TANs) as corrupted policemen in
      cancer may pave the way to innovative therapeutic strategies complementing
      cytoreductive therapies and immunotherapy. 

PMID- 26216633
TI  - Tumor-Elicited Inflammation and Colorectal Cancer.
AB  - The link between chronic inflammation and cancer has long been suspected, due to
      the pioneering work of Rudolf Virchow over 150 years ago. Yet the causal
      relationship between inflammation and cancer was only deciphered in the past
      decade or so, using animal models of various cancers. Up to 20% of all human
      cancers result from chronic inflammation and persistent infections.
      Proinflammatory cytokines and tumor-infiltrating myeloid and immune cells play
      critical roles in almost every developmental stages of inflammation-induced
      cancers, from initiation, promotion, and progression to malignant metastasis.
      However, even in cancers with no preceding inflammation, inflammatory cells
      infiltrate tumor stroma and contribute to cancer development. Such "tumor
      elicited inflammation" further emphasizes the importance of inflammation in
      different types of cancers, including that of the colon. In this review, we
      summarize our current knowledge of the function and induction mechanisms of
      inflammatory cytokines during colorectal cancer development, and hope to provide
      insight into the development of novel anticancer therapies by modulating tumor
      elicited inflammation. 

PMID- 26216631
TI  - Myeloid-Derived Suppressor Cells: Critical Cells Driving Immune Suppression in
      the Tumor Microenvironment.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of
      immature myeloid cells that suppress innate and adaptive immunity. MDSCs are
      present in many disease settings; however, in cancer, they are a major obstacle
      for both natural antitumor immunity and immunotherapy. Tumor and host cells in
      the tumor microenvironment (TME) produce a myriad of pro-inflammatory mediators
      that activate MDSCs and drive their accumulation and suppressive activity. MDSCs
      utilize a variety of mechanisms to suppress T cell activation, induce other
      immune-suppressive cell populations, regulate inflammation in the TME, and
      promote the switching of the immune system to one that tolerates and enhances
      tumor growth. Because MDSCs are present in most cancer patients and are potent
      immune-suppressive cells, MDSCs have been the focus of intense research in recent
      years. This review describes the history and identification of MDSCs, the role of
      inflammation and intracellular signaling events governing MDSC accumulation and
      suppressive activity, immune-suppressive mechanisms utilized by MDSCs, and recent
      therapeutics that target MDSCs to enhance antitumor immunity. 

PMID- 26216634
TI  - Therapeutic Lymphoid Organogenesis in the Tumor Microenvironment.
AB  - The inflammatory status of the tumor microenvironment (TME) has been heavily
      investigated in recent years. Chemokine- and cytokine-signaling pathways such as
      CCR7, CXCR5, lymphotoxin, and IL-36, which are involved in the generation of
      secondary lymphoid organs and effector immune responses, are now recognized as
      having value both as prognostic factors and as immunomodulatory therapeutics in
      the context of cancer. Furthermore, when produced in the TME, these mediators
      have been shown to promote the recruitment of immune cells, including T cells, B
      cells, dendritic cells (DCs), and other specialized immune cell subsets such as
      follicular DCs and T follicular helper cells, in association with the formation
      of "tertiary" lymphoid structures (TLSs) within or adjacent to sites of disease.
      Although TLSs are composed of a heterogeneous collection of immune cell types,
      whose composition differs based on cancer subtype, the qualitative presence of
      TLSs has been shown to represent a biomarker of good prognosis for cancer
      patients. A comprehensive understanding of the role each of these pathways plays
      within the TME may support the rational design of future immunotherapies to
      selectively promote/bolster TLS formation and function, leading to improved
      clinical outcomes across the vast range of solid cancer types.

PMID- 26216635
TI  - The Tumor Macroenvironment: Cancer-Promoting Networks Beyond Tumor Beds.
AB  - During tumor progression, alterations within the systemic tumor environment, or
      macroenvironment, result in the promotion of tumor growth, tumor invasion to
      distal organs, and eventual metastatic disease. Distally produced hormones,
      commensal microbiota residing within mucosal surfaces, myeloid cells and even the
      bone marrow impact the systemic immune system, tumor growth, and metastatic
      spread. Understanding the reciprocal interactions between the cells and soluble
      factors within the macroenvironment and the primary tumor will enable the design
      of specific therapies that have the potential to prevent dissemination and
      metastatic spread. This chapter will summarize recent findings detailing how the
      primary tumor and systemic tumor macroenvironment coordinate malignant
      progression. 

PMID- 26216638
TI  - Immunotherapy of Cancer. Preface.

PMID- 26216639
TI  - Biochemical characterization of a bifunctional acetaldehyde-alcohol dehydrogenase
      purified from a facultative anaerobic bacterium Citrobacter sp. S-77.
AB  - Acetaldehyde-alcohol dehydrogenase (ADHE) is a bifunctional enzyme consisting of
      two domains of an N-terminal acetaldehyde dehydrogenase (ALDH) and a C-terminal
      alcohol dehydrogenase (ADH). The enzyme is known to be important in the cellular
      alcohol metabolism. However, the role of coenzyme A-acylating ADHE responsible
      for ethanol production from acetyl-CoA remains uncertain. Here, we present the
      purification and biochemical characterization of an ADHE from Citrobacter sp. S
      77 (ADHE(S77)). Interestingly, the ADHE(S77) was unable to be solubilized from
      membrane with detergents either 1% Triton X-100 or 1% Sulfobetaine 3-12. However,
      the enzyme was easily dissociated from membrane by high-salt buffers containing
      either 1.0 M NaCl or (NH(4))(2)SO(4) without detergents. The molecular weight of
      a native protein was estimated as approximately 400 kDa, consisting of four
      identical subunits of 96.3 kDa. Based on the specific activity and kinetic
      analysis, the ADHES77 tended to have catalytic reaction towards acetaldehyde
      elimination rather than acetaldehyde formation. Our experimental observation
      suggests that the ADHES77 may play a pivotal role in modulating intracellular
      acetaldehyde concentration.

PMID- 26216636
TI  - Control of CD8 T-Cell Infiltration into Tumors by Vasculature and
      Microenvironment.
AB  - CD8 T-cells are a critical brake on the initial development of tumors. In
      established tumors, the presence of CD8 T-cells is correlated with a positive
      patient prognosis, although immunosuppressive mechanisms limit their
      effectiveness and they are rarely curative without manipulation. Cancer
      immunotherapies aim to shift the balance back to dominant antitumor immunity
      through antibody blockade of immunosuppressive signaling pathways, vaccination,
      and adoptive transfer of activated or engineered T-cells. These approaches have
      yielded striking responses in small subsets of patients with solid tumors, most
      notably those with melanoma. Importantly, the subset of patients who respond to
      vaccination or immunosuppression blockade therapies are those with CD8 T-cells
      present in the tumor prior to initiating therapy. While current adoptive cell
      therapy approaches can be dramatically effective, they require infusion of
      extremely large numbers of T-cells, but the number that actually infiltrates the
      tumor is very small. Thus, poor representation of CD8 T-cells in tumors is a
      fundamental hurdle to successful immunotherapy, over and above the well
      established barrier of immunosuppression. In this review, we discuss the factors
      that determine whether immune cells are present in tumors, with a focus on the
      representation of cytotoxic CD8 T-cells. We emphasize the critically important
      role of tumor-associated vasculature as a gateway that enables the active
      infiltration of both effector and naive CD8 T-cells that exert antitumor
      activity. We also discuss strategies to enhance the gateway function and extend
      the effectiveness of immunotherapies to a broader set of cancer patients. 

PMID- 26216640
TI  - Parastomal Hernia: Impact on Quality of Life?
AB  - INTRODUCTION: Parastomal hernia (PH) is a frequent complication after end
      colostomy formation. PH may negatively influence the quality of life in end
      colostomy patients. Our study investigates the quality of life and body image
      (BI) in patients with an end-colostomy. METHODS: We conducted a cross-sectional
      study of end-colostomy patients in two different hospitals. Patients were
      included if they had received a Hartmann procedure or abdominal perineal
      resection between 2004 and 2011. Patients were invited to the outpatient clinic
      for clinical examination to determine if a PH was present and were asked to fill
      out the Short form 36, EuroQol-5D, and body image questionnaire (BIQ). RESULTS:
      One-hundred-and-fifty patients were eligible for the study; 139 filled out the
      questionnaires, of which 79 (56.8 %) had developed a PH. A linear multivariate
      regression showed PH caused a decrease in physical functioning (difference -10.2,
      p = 0.033) and general health (difference -9.0, p = 0.021), increase in pain
      (difference -11.3, p = 0.009) and decrease in the overall physical component
      score (difference -4.8, p = 0.020). The BIQ showed that PH increased the shame of
      the scar (difference -0.4, p = 0.010). Having an incisional hernia simultaneously
      decreased patients' scoring of the scar in the BIQ (difference -0.99, p = 0.015).
      DISCUSSION: PHs cause significant decreases in quality of life and BI of
      patients. Counseling of patients towards PH and prevention of PH should therefore
      be of more concern in surgical departments.

PMID- 26216641
TI  - Erratum to: Safety and Hemostatic Effectiveness of the Fibrin Pad for Severe Soft
      Tissue Bleeding During Abdominal, Retroperitoneal, Pelvic, and Thoracic (Non
      cardiac) Surgery: A Randomized, Controlled, Superiority Trial.

PMID- 26216642
TI  - High Concentration of Calcium Stimulates Calcium Oxalate Crystal Attachment to
      Rat Tubular Epithelial NRK Cells Through Osteopontin.
AB  - OBJECTIVE: To address whether hypercalciuria can stimulate calcium oxalate (CaOx)
      crystal deposition in kidney through osteopontin (OPN). MATERIALS AND METHODS:
      Rat tubular epithelial NRK cells were exposed to calcium. The cell viability, the
      cellular malondialdehyde content as a marker of reactive oxygen species (ROS),
      and the release of lactate dehydrogenase as markers of injury were detected. The
      production and gene expression of OPN were also examined. CaOx crystal attachment
      to cells was accomplished by measuring the calcium concentration of the cell
      lysates with atomic absorption analysis. RESULTS: Exposure to calcium produced
      signs of cell injury and ROS-induced lipid peroxidation. The messenger
      ribonucleic acid expression and production of OPN increased significantly. OPN
      knockdown can significantly decrease the amount of CaOx crystal attachment to NRK
      cells. CONCLUSION: In response to exposure to high concentration of calcium,
      renal tubular epithelial NRK cells increase the production of OPN, which may have
      a promoting role in CaOx crystal adhesion to NRK cells by calcium stimulation.

PMID- 26216643
TI  - Practice Patterns in the Treatment of Urethral Stricture Among American
      Urologists: A Paradigm Change?
AB  - OBJECTIVE: To examine surgical case volume characteristics among certifying
      urologists associated with treatment of urethral stricture to compare practice
      patterns of recent graduates to recertifying attending urologists and trends over
      time. MATERIALS AND METHODS: Six-month case log data of certifying and
      recertifying urologists (2003-2013) were obtained from the American Board of
      Urology. Cases specifying a CPT code for urethral dilation, direct vision
      internal urethrotomy (DVIU), urethroplasty, and graft harvest in males >=18 years
      were analyzed for surgeon-specific variables. RESULTS: Among 6320 urologists
      logging at least one reconstructive urology procedure, 95,747 (86.2%) urethral
      dilations, 10,986 (10.0%) DVIU, and 4349 (3.9%) urethroplasties were identified,
      with 99 (0.9%) using graft and 405 (9.3%) staged procedures. Overall ratio of
      urethral dilation/DVIU to urethroplasty was 24.5:1. More recent log year and new
      certification correlated with a decrease in ratio of dilation/DVIU to
      urethroplasty, but stable use of graft. The ratio of dilation/DVIU to
      urethroplasty for new certification was much lower (7.9:1), compared to first
      (24.4:1), second (63.3:1), and third recertification cycles (99.5:1), wherein
      urethroplasty was increasingly rare. Newly certifying urologists performed
      urethroplasty 4.5 times more often than those recertifying. Academically
      affiliated urologists were 8 times more likely to perform urethroplasty.
      CONCLUSION: Most urethral strictures are treated with dilation/DVIU, but a
      changing paradigm favoring urethroplasty is evident. Most urethroplasties are
      performed by a small number of urologists with high volume, academic affiliation,
      recent residency graduation, and residence in a state with a reconstructive
      urology fellowship.

PMID- 26216637
TI  - Scavenger Receptors: Emerging Roles in Cancer Biology and Immunology.
AB  - Scavenger receptors constitute a large family of evolutionally conserved protein
      molecules that are structurally and functionally diverse. Although scavenger
      receptors were originally identified based on their capacity to scavenge modified
      lipoproteins, these molecules have been shown to recognize and bind to a broad
      spectrum of ligands, including modified and unmodified host-derived molecules or
      microbial components. As a major subset of innate pattern recognition receptors,
      scavenger receptors are mainly expressed on myeloid cells and function in a wide
      range of biological processes, such as endocytosis, adhesion, lipid transport,
      antigen presentation, and pathogen clearance. In addition to playing a crucial
      role in maintenance of host homeostasis, scavenger receptors have been implicated
      in the pathogenesis of a number of diseases, e.g., atherosclerosis,
      neurodegeneration, or metabolic disorders. Emerging evidence has begun to reveal
      these receptor molecules as important regulators of tumor behavior and host
      immune responses to cancer. This review summarizes our current understanding on
      the newly identified, distinct functions of scavenger receptors in cancer biology
      and immunology. The potential of scavenger receptors as diagnostic biomarkers and
      novel targets for therapeutic interventions to treat malignancies is also
      highlighted. 

PMID- 26216644
TI  - Efficacy and Safety of Rezum System Water Vapor Treatment for Lower Urinary Tract
      Symptoms Secondary to Benign Prostatic Hyperplasia.
AB  - OBJECTIVE: To assess 1-year efficacy and safety data from pilot trials of the
      Rezum System water vapor to treat lower urinary tract symptoms (LUTS) secondary
      to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 65 men
      with symptoms of moderate to severe BPH were enrolled in pilot studies at centers
      in the Dominican Republic, the Czech Republic, and Sweden. Each patient was
      treated with transurethral delivery of sterile water vapor (steam). International
      Prostate Symptom Score (IPSS), peak urinary flow (Qmax), quality of life (QoL),
      postvoid residual, International Index of Erectile Function, and prostate
      specific antigen were evaluated at 1 week and 1, 3, 6, and 12 months post
      treatment. Safety was also assessed. RESULTS: Statistically significant clinical
      improvements at 1, 3, 6, and 12 months were reported for IPSS (decreased by 6.8,
      13.4, 13.1, and 12.5 points, respectively) and Qmax (increased by 2.0, 4.7, 4.3,
      and 4.6 mL/sec, respectively). At 12 months, these results equated to a 56%
      improvement in IPSS (P <.001) and an 87% improvement in Qmax (P <.001). QoL also
      improved at 12 months with a 61% improvement. Sexual function was maintained.
      Most of the adverse events (AEs) were related to endoscopic instrumentation and
      were of short duration. One case of urinary retention was classified as a
      procedure/device-related serious AE. CONCLUSION: The Rezum System provides
      effective relief of LUTS associated with BPH at 1 year. The procedure is safe
      with an acceptable side effect profile.

PMID- 26216645
TI  - Symmetry in the pigeon with sample and comparison stimuli in different locations.
      II.
AB  - Pigeons were trained on arbitrary (hue-form) and identity (hue-hue and form-form)
      successive matching with center-key samples and left-key comparisons. Later, they
      were tested on form-hue (symmetry) probe trials that were structured either in
      the different-locations fashion as the baseline trials (viz., center-key samples
      and left-key comparisons) or with a constant location by using center-key samples
      and center-key comparisons. Three of four pigeons showed symmetry when the probe
      trial samples and comparisons appeared in center- and left-key spatial locations,
      respectively, but none did when both appeared in one (center-key) location.
      Subsequently, pigeons previously tested with center-key samples and left-key
      comparisons were tested with those form-hue stimuli shown in the same (center
      key) location, and vice versa for the other pigeons. None of the former pigeons
      showed symmetry on the second test even if they had on the first test. By
      contrast, two of three pigeons that had not shown symmetry with single-location
      samples and comparisons did so when those stimuli appeared in different (center-
      vs. left-key) locations. Taken together, these results show that symmetrical
      relations between the same, nominal matching stimuli depend on where those
      stimuli appear in testing vis-a-vis in training and, more generally, confirm that
      spatial location is part of the functional matching stimuli. 

PMID- 26216646
TI  - Arabidopsis thaliana ggt1 photorespiratory mutants maintain leaf carbon/nitrogen
      balance by reducing RuBisCO content and plant growth.
AB  - Metabolic and physiological analyses of glutamate:glyoxylate aminotransferase 1
      (GGT1) mutants were performed at the global leaf scale to elucidate the
      mechanisms involved in their photorespiratory growth phenotype. Air-grown ggt1
      mutants showed retarded growth and development, that was not observed at high CO2
      (3000 MUL L(-1) ). When compared to wild-type (WT) plants, air-grown ggt1 plants
      exhibited glyoxylate accumulation, global changes in amino acid amounts including
      a decrease in serine content, lower organic acid levels, and modified ATP/ADP and
      NADP(+) /NADPH ratios. When compared to WT plants, their net CO2 assimilation
      rates (An ) were 50% lower and this mirrored decreases in ribulose-1,5
      bisphosphate carboxylase/oxygenase (RuBisCO) contents. High CO2 -grown ggt1
      plants transferred to air revealed a rapid decrease of An and photosynthetic
      electron transfer rate while maintaining a high energetic state. Short-term (a
      night period and 4 h of light) transferred ggt1 leaves accumulated glyoxylate and
      exhibited low serine contents, while other amino acid levels were not modified.
      RuBisCO content, activity and activation state were not altered after a short
      term transfer while the ATP/ADP ratio was lowered in ggt1 rosettes. However,
      plant growth and RuBisCO levels were both reduced in ggt1 leaves after a long
      term (12 days) acclimation to air from high CO2 when compared to WT plants. The
      data are discussed with respect to a reduced photorespiratory carbon recycling in
      the mutants. It is proposed that the low An limits nitrogen-assimilation, this
      decreases leaf RuBisCO content until plants attain a new homeostatic state that
      maintains a constant C/N balance and leads to smaller, slower growing plants. 

PMID- 26216647
TI  - Oxidized Zirconium Bearing Surfaces in Total Knee Arthroplasty: Lessons Learned.
AB  - Polyethylene wear in total knee arthroplasty is a still unsolved problem
      resulting in osteolysis and long-term failure of knee joint replacement. To
      address the problem of polyethylene wear, research aimed for an optimal implant
      design and for an optimal combination of bearing surfaces. Oxidized zirconium was
      introduced to minimize surface wear and thus potentially increase long-term
      implant survival. This review comprises the current literature related to in
      vitro and in vivo studies evaluating performance of oxidized zirconium total knee
      arthroplasty and results from retrieval analyses. 

PMID- 26216648
TI  - n-3 polyunsaturated fatty acid supplementation reduces insulin resistance in
      hepatitis C virus infected patients: a randomised controlled trial.
AB  - BACKGROUND: Insulin resistance promotes liver disease progression and may be
      associated with a lower response rate in treated hepatitis C virus (HCV) infected
      patients. n-3 polyunsaturated fatty acid (PUFA) supplementation may reduce
      insulin resistance. The present study aimed to evaluate the effect of n-3 PUFA
      supplementation on insulin resistance in these patients. METHODS: In a
      randomised, double-blind clinical trial, 154 patients were screened. After
      applying inclusion criteria, 52 patients [homeostasis model assessment index of
      insulin resistance (HOMA-IR >=2.5)] were randomly divided into two groups: n-3
      PUFA (n = 25/6000 mg day(-1) of fish oil) or control (n = 27/6000 mg day(-1) of
      soybean oil). Both groups were supplemented for 12 weeks and underwent monthly
      nutritional consultation. Biochemical tests were performed at baseline and after
      intervention. Statistical analysis was performed using the Wilcoxon Mann-Whitney
      test for comparisons and the Wilcoxon test for paired data. Statistical package
      r, version 3.02 (The R Project for Statistical Computing) was used and P < 0.05
      (two-tailed) was considered statistically significant. RESULTS: Comparisons
      between groups showed that n-3 PUFA supplementation was more effective than the
      control for reducing HOMA-IR (P = 0.015) and serum insulin (P = 0.016). The n-3
      PUFA group not only showed a significant reduction in HOMA-IR 3.8 (3.2-5.0)
      versus 2.4 (1.8-3.3) (P = 0.002); serum insulin 17.1 (13.8-20.6) MUIU mL(-1)
      versus 10.9 (8.6-14.6) MUIU mL(-1) (P = 0.001); and glycated haemoglobin 5.4%
      (5.0-5.7%) versus 5.1% (4.8-5.6%) (P = 0.011), but also presented an increase in
      interleukin-1 97.5 (0.0-199.8) pg mL(-1) versus 192.4 (102.2-266.8) pg mL(-1) (P
      = 0.003) and tumour necrosis factor 121.2 (0.0-171.3) pg mL(-1) versus 185.7
      (98.0-246.9) pg mL(-1) (P = 0.003). CONCLUSIONS: n-3 PUFA supplementation reduces
      insulin resistance in genotype 1 HCV infected patients.

PMID- 26216649
TI  - Comparison of the reliability of E/E' to estimate pulmonary capillary wedge
      pressure in heart failure patients with preserved ejection fraction versus those
      with reduced ejection fraction.
AB  - Accurate assessment of pulmonary capillary wedge pressure (PCWP) is essential for
      physicians to effectively manage patients with acute decompensated heart failure.
      The ratio of early transmittal velocity to tissue Doppler mitral annular early
      diastolic velocity (E/E') is used to estimate PCWP noninvasively in a wide range
      of cardiac patients. However, it remains contentious as to whether mitral E/E' is
      a reliable predictor of PCWP. In the present study, acute heart failure patients
      were divided into two groups on the basis of left ventricular (LV) systolic
      function: those with preserved ejection fraction (HFpEF) and those with reduced
      ejection fraction (HFrEF). The usefulness of mitral E/E' in estimating PCWP was
      compared between the two groups. Fifty consecutive patients who were admitted
      with acute decompensated heart failure and underwent both right-sided cardiac
      catheterization and transthoracic echocardiography during hospitalization were
      analyzed retrospectively. Pearson's correlation was used to evaluate associations
      between Doppler parameters and PCWP. E/E' was positively correlated with PCWP (r
      = 0.56, P = 0.01) in the heart failure with preserved ejection fraction group.
      However, no significant relationship was observed between PCWP and mitral E/E' (P
      = 0.85) in the heart failure with reduced ejection fraction group. There were no
      significant correlations between any of the conventional parameters considered
      (LVEF, left atrial dimension, E/A, IVRT, and DT) with PCWP in either group. In
      conclusion, mitral E/E' is useful for estimating PCWP in patients with acute
      heart failure with preserved ejection fraction but may not in those with reduced
      ejection fraction.

PMID- 26216650
TI  - Readiness for Hospital Discharge Scale for older people: psychometric testing and
      short form development with a three country sample.
AB  - AIM: To develop and psychometrically test Readiness for Hospital Discharge Scale
      for older people and to reduce the scale to a more practical short form.
      BACKGROUND: The Readiness for Hospital Discharge Scale is the only available and
      validated scale measuring patients' perceived readiness just prior to discharge.
      DESIGN: Secondary analysis of hospital studies data from three countries. METHOD:
      Data were collected between 2008-2012. The study sample comprised 998 medical
      surgical older patients. Factor analysis was undertaken to identify the factor
      structure of the Readiness for Hospital Discharge Scale. Group comparisons for
      construct validity and predictive validity for readmission were also conducted.
      RESULTS: The Readiness for Hospital Discharge Scale original four factor solution
      does not appear to be consistent with the observed data of older people in the
      three countries. Confirmatory factor analysis revealed that a 17-item scale with
      three factors produced the best model fit. Nine items, three from each factor,
      loaded consistently on their respective factors in each country sample.
      Confirmatory factor analysis of this short form model indicated that the model
      adequately fit the data. Patients who lived alone, were older, or who indicated
      'not ready' for discharge had lower Readiness for Hospital Discharge Scale for
      Older People scores, which were also associated with readmission risk.
      CONCLUSION: The revised three factor structure of the Readiness for Hospital
      Discharge Scale for Older People in long and short forms more adequately assesses
      core components of discharge readiness in the older adult population than the
      original adult form.

PMID- 26216651
TI  - Endoscopic and clinical evaluation of treatment and prognosis of Cronkhite-Canada
      syndrome: a Japanese nationwide survey.
AB  - BACKGROUND: First reported in 1955, Cronkhite-Canada syndrome (CCS), a rare
      syndrome characterized by ectodermal abnormalities and inflammatory changes of
      the gastrointestinal tract mucosa, has been associated with a poor prognosis and
      life-threatening malignant complications. In a large population survey, we
      endeavored to characterize the course and treatment outcome of CCS through
      clinical and endoscopic assessment, and to explore its optimal treatment and
      surveillance strategy. METHODS: A retrospective analysis of 210 patients with CCS
      was conducted via a questionnaire-based nationwide survey of 983 teaching
      hospitals located throughout Japan. We assessed clinical features, endoscopic
      findings, treatments used, and short- and long-term outcomes. RESULTS: The
      average age at diagnosis was 63.5 years. In all cases, upper or lower
      gastrointestinal tract polyposis was confirmed, accompanied by characteristic
      ectodermal abnormalities. Of the treatments used, oral corticosteroids (30-49
      mg/day) were the most effective treatment for active disease, with adjunctive
      nutritional support considered beneficial. With corticosteroid treatment,
      abdominal symptoms were relieved within a few months, whereas polyp regression
      often required more than 6 months. Maintenance of endoscopic remission with or
      without steroids for 3 years significantly lowered the development of CCS-related
      cancer, compared with relapsers or nonresponders, underscoring the importance of
      sustained endoscopic remission for cancer prevention. CONCLUSIONS: The prognosis
      of CCS has greatly improved through the use of improved medical treatment.
      Although CCS continues to be relentlessly progressive, carrying a high cancer
      risk, a sufficient dose and duration of corticosteroid therapy accompanied by
      nutritional support and periodic endoscopic surveillance appears to improve its
      natural history.

PMID- 26216652
TI  - Endovascular Treatment of Acute Stroke: Evolution and Selection of Techniques and
      Instruments Based on Thrombus Imaging.
AB  - Mechanical thrombectomy provides higher recanalization rates than intravenous or
      intra-arterial thrombolysis. Finally this has been shown to translate into
      improved clinical outcome in six multicentric randomized controlled trials.
      However, within cohorts the clinical outcomes may vary, depending on the
      endovascular techniques applied. Systems aiming mainly for thrombus fragmentation
      and lacking a protection against distal embolization have shown disappointing
      results when compared to recent stent-retriever studies or even to historical
      data on local arterial fibrinolysis. Procedure-related embolic events are usually
      graded as adverse events in interventional neuroradiology. In stroke, however,
      the clinical consequences of secondary emboli have so far mostly been neglected
      and attributed to progression of the stroke itself. We summarize the evolution of
      instruments and techniques for endovascular, image-guided, microneurosurgical
      recanalization in acute stroke, and discuss how to avoid procedure-related
      embolic complications. 

PMID- 26216653
TI  - Imaging Neurodegeneration: Steps Toward Brain Network-Based Pathophysiology and
      Its Potential for Multi-modal Imaging Diagnostics.
AB  - PURPOSE: Multi-modal brain imaging provides different in vivo windows into the
      human brain and thereby different ways to characterize brain disorders.
      Particularly, resting-state functional magnetic resonance imaging facilitates the
      study of macroscopic intrinsic brain networks, which are critical for development
      and spread of neurodegenerative processes in different neurodegenerative
      diseases. The aim of the current study is to present and highlight some
      paradigmatic findings in intrinsic network-based pathophysiology of
      neurodegenerative diseases and its potential for new network-based multimodal
      tools in imaging diagnostics. METHODS: Qualitative review of selected multi-modal
      imaging studies in neurodegenerative diseases particularly in Alzheimer's disease
      (AD). RESULTS: Functional connectivity of intrinsic brain networks is selectively
      and progressively impaired in AD, with changes likely starting before the onset
      of symptoms in fronto-parietal key networks such as default mode or attention
      networks. Patterns of distribution and development of both amyloid-beta plaques
      and atrophy are linked with network connectivity changes, suggesting that start
      and spread of pathology interacts with network connectivity. Qualitatively
      similar findings have been observed in other neurodegenerative disorders,
      suggesting shared mechanisms of network-based pathophysiology across diseases.
      CONCLUSION: Spread of neurodegeneration is intimately linked with the functional
      connectivity of intrinsic brain networks. These pathophysiological insights pave
      the way for new multi-modal network-based tools to detect and characterize
      neurodegeneration in individual patients.

PMID- 26216654
TI  - Biomimetic Self-Healing.
AB  - Self-healing is a natural process common to all living organisms which provides
      increased longevity and the ability to adapt to changes in the environment.
      Inspired by this fitness-enhancing functionality, which was tuned by billions of
      years of evolution, scientists and engineers have been incorporating self-healing
      capabilities into synthetic materials. By mimicking mechanically triggered
      chemistry as well as the storage and delivery of liquid reagents, new materials
      have been developed with extended longevity that are capable of restoring
      mechanical integrity and additional functions after being damaged. This Review
      describes the fundamental steps in this new field of science, which combines
      chemistry, physics, materials science, and mechanical engineering. 

PMID- 26216655
TI  - Infantile Hepatic Hemangioma: Role of Dynamic Contrast-Enhanced Magnetic
      Resonance Angiography.

PMID- 26216656
TI  - The JAK2 V617F mutational status and allele burden--authors' reply.

PMID- 26216657
TI  - Understanding of the low temperature auto-oxidation scheme of sec-alcohols based
      on a Cu(II)-MOF with open metal sites.
AB  - A Cu(II)-MOF (1') with open metal sites was readily obtained by removing the
      coordinated water molecule at 120  degrees C. It can be used as a probe to
      evidence the sec-alkyl hydroperoxide species generated from room temperature sec
      alcohol auto-oxidation in air. The formed alkyl hydroperoxides can be effectively
      catalyzed by 1' to decompose into molecular oxygen and corresponding sec-alcohols
      under ambient conditions.

PMID- 26216658
TI  - Accuracy and reproducibility of linear measurements of resin, plaster, digital
      and printed study-models.
AB  - OBJECTIVES: To compare the accuracy and reproducibility of measurements of on
      screen three-dimensional (3D) digital surface models captured by a 3Shape R700TM
      laser-scanner, with measurements made using a digital caliper on acrylic, plaster
      models or model replicas. SUBJECTS AND METHOD: Four sets of typodont models were
      used. Acrylic models, alginate impressions, plaster models and physical replicas
      were measured. The 3Shape R700TM laser-scanning device with 3ShapeTM software was
      used for scans and measurements. Linear measurements were recorded for selected
      landmarks, on each of the physical models and on the 3D digital surface models on
      ten separate occasions by a single examiner. RESULTS: Comparing measurements
      taken on the physical models the mean difference of the measurements was 0.32 mm
      (SD 0.15 mm). For the different methods (physical versus digital) the mean
      difference was 0.112 mm (SD 0.15 mm). None of the values showed a statistically
      significant difference (p < 0.05) on the Objet Eden 250TM 3D prints, alginate
      impressions, plaster and acrylic models. CONCLUSION: The comparison of
      measurements on the physical models showed no significant difference. The 3Shape
      R700TM is a reliable device for capturing surface details of models in a digital
      format. When comparing measurements taken manually and digitally there was no
      statistically significant difference. The Objet Eden 250TM 3D prints proved to be
      as accurate as the original acrylic, plaster, or alginate impressions as was
      shown by the accuracy of the measurements taken. This confirms that using virtual
      study models can be a reliable method, replacing traditional plaster models.

PMID- 26216659
TI  - Working with culturally and linguistically diverse students and their families:
      perceptions and practices of school speech-language therapists in the United
      States.
AB  - BACKGROUND: Speech and language therapists (SLTs) working in schools worldwide
      strive to deliver evidence-based services to diverse populations of students.
      Many suggestions have been made in the international professional literature
      regarding culturally competent delivery of speech and language services, but
      there has been limited qualitative investigation of practices school SLTs find to
      be most useful when modifying their approaches to meet the needs of culturally
      and linguistically diverse (CLD) students. AIMS: To examine perceptions of nine
      school SLTs regarding modifications of usual practices when interacting with CLD
      students and their families; to compare reported practices with those suggested
      in professional literature; to draw clinical implications regarding the results;
      and to suggest future research to build a more extensive evidence base for
      culturally competent service delivery. METHODS & PROCEDURES: For this qualitative
      research study, nine school SLTs in a diverse region of the USA were recruited to
      participate in a semi-structured interview designed to answer the question: What
      dominant themes, if any, can be found in SLTs' descriptions of how they modify
      their approaches, if at all, when interacting with CLD students and their family
      members? OUTCOMES & RESULTS: Analysis of data revealed the following themes: (1)
      language-a barrier and a bridge, (2) communicating through interpreters, (3)
      respect for cultural differences, and (4) positive experiences interacting with
      CLD family members. CONCLUSIONS & IMPLICATIONS: Participants reported making many
      modifications to their usual approaches that have been recommended as best
      practices in the international literature. However, some practices the SLTs
      reported to be effective were not emphasized or were not addressed at all in the
      literature. Practical implications of results are drawn and future research is
      suggested.

PMID- 26216660
TI  - A Bayesian model of psychosis symptom trajectory in Alzheimer's disease.
AB  - OBJECTIVE: Psychosis, like other neuropsychiatric symptoms of dementia, has many
      features that make predictive modeling of its onset difficult. For example,
      psychosis onset is associated with both the absolute degree of cognitive
      impairment and the rate of cognitive decline. Moreover, psychotic symptoms, while
      more likely than not to persist over time within individuals, may remit and
      recur. To facilitate predictive modeling of psychosis for personalized clinical
      decision making, including evaluating the role of risk genes in its onset, we
      have developed a novel Bayesian model of the dual trajectories of cognition and
      psychosis symptoms. METHODS: Cognition was modeled as a four-parameter logistic
      curve with random effects for all four parameters and possible covariates for the
      rate and time of fall. Psychosis was modeled as a continuous-time hidden Markov
      model with a latent never-psychotic class and states for pre-psychotic, actively
      psychotic and remitted psychosis. Covariates can affect the probability of being
      in the never-psychotic class. Covariates and the level of cognition can affect
      the transition rates for the hidden Markov model. RESULTS: The model
      characteristics were confirmed using simulated data. Results from 434 AD patients
      show that a decline in cognition is associated with an increased rate of
      transition to the psychotic state. CONCLUSIONS: The model allows declining
      cognition as an input for psychosis prediction, while incorporating the full
      uncertainty of the interpolated cognition values. The techniques used can be used
      in future genetic studies of AD and are generalizable to the study of other
      neuropsychiatric symptoms in dementia.

PMID- 26216661
TI  - Illness Perception and Well-Being Among Persons with Multiple Sclerosis and Their
      Caregivers.
AB  - This study jointly examined illness beliefs held by persons with multiple
      sclerosis (PwMS) and caregivers in relation to well-being. A group of 68 PwMS and
      their caregivers completed the Revised Illness Perception Questionnaire,
      Psychological Well-being Scales, Satisfaction with Life Scale and Positive Affect
      and Negative Affect Schedule. Findings revealed that PwMS' well-being was
      primarily predicted by their own illness beliefs, and that also caregivers' well
      being was primarily predicted by their own beliefs. Across the two groups, well
      being was positively associated with their belief that they understood the
      disease, and inversely associated with their representations of negative
      emotions. In addition, among PwMS, well-being was inversely associated with the
      number of symptoms they specifically attributed to their illness, while among
      caregivers, well-being was positively associated with beliefs that treatment
      could control the disease. Based on the study findings, psychoeducational and
      cognitive-behavioral strategies are suggested to promote well-being among PwMS
      and caregivers. 

PMID- 26216663
TI  - Longitudinal changes in the DTI measures, anti-GFAP expression and levels of
      serum inflammatory cytokines following mild traumatic brain injury.
AB  - The majority of human mild traumatic brain injuries (mTBI; 70%) lack radiological
      evidence of injury, yet may present long term cognitive, and behavioral
      dysfunctions. With the hypothesis of evident damaged neural tissue and
      immunological consequences during acute phase of mTBI, we used closed skull
      weight-drop TBI model to address human mTBI condition. Serum cytokines (TNF
      alpha, IL-10) and glial fibrillary acidic protein (GFAP) expression were examined
      at day 0 (control, pre-injury), 4h, day 1, day 3 and day 5 post injury (PI).
      Diffusion tensor imaging (DTI) was performed at similar timepoints to identify
      neuroinflammation translation into imaging abnormalities and monitor injury
      progression. DTI indices including mean diffusivity (MD), radial diffusivity
      (RD), fractional anisotropy and axial diffusivity values were quantified from
      cortex (CTX), hippocampus and corpus callosum regions. One way ANOVA showed
      significant increase in TNF-alpha at 4h and IL-10 at day 1 PI as compared to
      control. GFAP(+) cells were significantly increased at day 3 and day 5 as
      compared to control in CTX. Repeated measures ANOVA revealed significant
      decreases in MD, RD values in CTX at day 3 and day 5 as compared to day 0. A
      significant, inverse correlation was observed between cortical MD (r=-0.74,
      p=0.01), AD (r=-0.60, p=0.03) and RD (r=-0.72, p=0.01) values with mean GFAP(+)
      cells in the cortical region. These findings suggest that mTBI leads to elevated
      cytokine expression and subsequent hypertrophy of astrocytic processes. The
      increased numbers of reactive glial cells contribute diffusion restrictions in
      the CNS leading to reduced MD and RD values. These findings are in line with the
      deficits and pathologies associated with clinical mTBI, and support the use of
      mTBI model to address pathology and therapeutic options. 

PMID- 26216662
TI  - Human iPS cell-derived astrocyte transplants preserve respiratory function after
      spinal cord injury.
AB  - Transplantation-based replacement of lost and/or dysfunctional astrocytes is a
      promising therapy for spinal cord injury (SCI) that has not been extensively
      explored, despite the integral roles played by astrocytes in the central nervous
      system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant
      source of pluripotent cells that both avoid ethical issues of embryonic stem
      cells and allow for homogeneous derivation of mature cell types in large
      quantities, potentially in an autologous fashion. Despite their promise, the iPS
      cell field is in its infancy with respect to evaluating in vivo graft integration
      and therapeutic efficacy in SCI models. Astrocytes express the major glutamate
      transporter, GLT1, which is responsible for the vast majority of glutamate uptake
      in spinal cord. Following SCI, compromised GLT1 expression/function can increase
      susceptibility to excitotoxicity. We therefore evaluated intraspinal
      transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical
      contusion SCI as a novel strategy for reconstituting GLT1 expression and for
      protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells
      showed robust long-term survival post-injection and efficiently differentiated
      into astrocytes in injured spinal cord of both immunesuppressed mice and rats.
      However, the majority of transplant-derived astrocytes did not express high
      levels of GLT1, particularly at early times post-injection. To enhance their
      ability to modulate extracellular glutamate levels, we engineered hIPSAs with
      lentivirus to constitutively express GLT1. Overexpression significantly increased
      GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both
      in vitro and in vivo post-transplantation. Compared to human fibroblast control
      and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1)
      lesion size within the injured cervical spinal cord, (2) morphological
      denervation by respiratory phrenic motor neurons at the diaphragm neuromuscular
      junction, and (3) functional diaphragm denervation as measured by recording of
      spontaneous EMGs and evoked compound muscle action potentials. Our findings
      demonstrate that hiPSA transplantation is a therapeutically-powerful approach for
      SCI. 

PMID- 26216664
TI  - Brain gliomas presenting with symptoms of spinal cord metastasis.
AB  - Three patients with brain gliomas (aged 41, 37, and 43 years) presented spinal
      cord symptoms as first neurological presentation (two cases) or at anaplastic
      progression (one case). Histologically, two cases were anaplastic (WHO III)
      astrocytomas and one anaplastic (WHO III) oligodendroglioma. The spinal surgery
      consisted of partial tumor resection in two cases with localized spinal cord
      metastasis, and tumor biopsy in another with diffuse spreading to the conus and
      cauda. Spinal irradiation was performed in one case. The time interval between
      the spinal surgery and the appearance of brain symptoms was very short (1 month
      or less). Two patients underwent brain surgery (tumor resection in one and
      stereotactic biopsy in another). The survival time was very short (2 and 3
      months) in the two patients with anaplastic astrocytoma, whereas the patient with
      anaplastic oligodendroglioma survived 1 year after the spinal surgery. Brain
      gliomas may exceptionally present with symptoms of a spinal cord metastasis. The
      magnetic resonance imaging finding of a spinal cord enhancing lesion,
      particularly if associated with root enhancement, should suggest the presence of
      a brain glioma. In cases with a localized spinal lesion, an early spinal surgery
      is advised for both diagnosis and decompression of the nervous structures.
      However, the clinical outcome is poor and the survival time is short.

PMID- 26216665
TI  - Challenges with AST/ALT ratio in acetaminophen poisoning.

PMID- 26216666
TI  - Identification of a novel HLA-B*40 variant allele, B*40:301, by sequence-based
      typing.
AB  - The new allele, HLA-B*40:301 differs from B*40:01:02 by one nucleotide
      substitution at codon 239 (AGA -> AAA). 

PMID- 26216667
TI  - Cavity Ring Down Spectroscopy Measurements for High-Overtone Vibrational Bands of
      HC3N.
AB  - Overtone (5nu1 and 6nu1) and combination (4nu1 + nu3 and 4nu1 + nu2) vibrational
      bands of gaseous HC3N, located in the visible range (14,600-15,800 and 17,400
      18,600 cm(-1)), were investigated by cavity ring-down absorption spectroscopy.
      The 5nu1 + nu3 and 5nu1 + nu2 combinations as well as the 6nu1 + nu5 - nu5 hot
      overtone band have also been identified, on the basis of previous overtone
      assignments. Absolute integrated intensity values and the ensuing oscillator
      strengths have been measured here for the first time; f values are typically
      confined between 4 * 10(-12) and 7 * 10(-11). For the even weaker 5nu1 + nu2
      combination band, the oscillator strength was estimated as 9 * 10(-13). The
      values concerning CH-stretch overtones (nnu1) are similar to those found in the
      literature for HCN and C2H2, the molecules with sp-hybridized carbon atoms. Data
      presented here may prove useful for studying the photochemistry triggered with
      visible or near-IR radiation within the atmospheres of certain Solar System
      bodies, including Titan.

PMID- 26216668
TI  - The Use of a Modified Poly-Ether-Ether-Ketone (PEEK) as an Alternative Framework
      Material for Removable Dental Prostheses. A Clinical Report.
AB  - This clinical report presents a modified poly-ether-ether-ketone (PEEK) as an
      alternative material for the fabrication of distal extension removable dental
      prosthesis (RDP) frameworks. This material can be used for patients allergic to
      metals, or who dislike the metallic taste, the weight, and the unpleasant metal
      display of the denture framework and retentive clasps. This modified PEEK
      material, known as BioHPP, is a biocompatible, nonallergic, rigid material, with
      flexibility comparable to bone, high polishing and low absorption properties, low
      plaque affinity, and good wear resistance. It has been used for years in
      orthopedics and medical technology. BioHPP frameworks can be constructed either
      via CAD/CAM manufacturing or via the conventional lost wax technique. The
      clinical use of a BioHPP RDP framework is presented as an alternative for the
      treatment of a distal extension case.

PMID- 26216669
TI  - Large-scale controlled fabrication of highly roughened flower-like silver
      nanostructures in liquid crystalline phase.
AB  - Large-scale controllable fabrication of highly roughened flower-like silver
      nanostructures is demonstrated experimentally via electrodeposition in the liquid
      crystalline phase. Different sizes of silver flowers are fabricated by adjusting
      the deposition time and the concentration of the silver nitrate solution. The
      density of the silver flowers in the sample is also controllable in this work.
      The flower-like silver nanostructures can serve as effective surface-enhanced
      Raman scattering and surface-enhanced fluorescence substrates because of their
      local surface plasmon resonance, and they may have applications in
      photoluminescence and catalysis. This liquid crystalline phase is used as a soft
      template for fabricating flower-like silver nanostructures for the first time,
      and this approach is suitable for large-scale uniform fabrication up to several
      centimetres. 

PMID- 26216670
TI  - International warfarin genotype-guided dosing algorithms in the Turkish
      population and their preventive effects on major and life-threatening hemorrhagic
      events.
AB  - AIM: To determine the accuracy of international warfarin pharmacogenetic
      algorithms developed on large multiethnic cohorts (comprising more than 1000
      subjects) to predict therapeutic warfarin doses in Turkish patients. MATERIALS &
      METHODS: We investigated two Turkish warfarin-treated cohorts: patients with no
      history of hemorrhagic or thromboembolic event and patients with major and life
      threatening hemorrhagic events. RESULTS: International pharmacogenetic algorithms
      showed good performances in predicting the therapeutic dose of patients with no
      history of bleedings, but they did not significantly detect the incorrect
      warfarin dose of patients with major and life-threatening hemorrhagic events.
      CONCLUSION: Although genetic information can predict the therapeutic warfarin
      dose, the accuracy of the international pharmacogenetic algorithms is not
      sufficient to be used for warfarin screening in Turkish patients.

PMID- 26216671
TI  - Commentary to: Cost of poor adherence to anti-hypertensive therapy in five
      European countries.

PMID- 26216672
TI  - Functional analysis of the role of glutathione peroxidase (GPx) in the ROS
      signaling pathway, hyphal branching and the regulation of ganoderic acid
      biosynthesis in Ganoderma lucidum.
AB  - Ganoderma lucidum, a hallmark of traditional Chinese medicine, has been widely
      used as a pharmacologically active compound. Although numerous research studies
      have focused on the pharmacological mechanism, fewer studies have explored the
      basic biological features of this species, restricting the further development
      and application of this important mushroom. Because of the ability of this
      mushroom to reduce and detoxify the compounds produced by various metabolic
      pathways, glutathione peroxidase (GPx) is one of the most important antioxidant
      enzymes with respect to ROS. Although studies in both animals and plants have
      suggested many important physiological functions of GPx, there are few systematic
      research studies concerning the role of this enzyme in fungi, particularly in
      large basidiomycetes. In the present study, we cloned the GPx gene and created
      GPx-silenced strains by the down-regulation of GPx gene expression using RNA
      interference. The results indicated an essential role for GPx in controlling the
      intracellular H2O2 content, hyphal branching, antioxidant stress tolerance,
      cytosolic Ca(2+) content and ganoderic acid biosynthesis. Further mechanistic
      investigation revealed that GPx is regulated by intracellular H2O2 levels and
      suggested that crosstalk occurs between GPx and intracellular H2O2. Moreover,
      evidence was obtained indicating that GPx regulation of hyphal branching via ROS
      might occur independently of the cytosolic Ca(2+) content. Further mechanistic
      investigation also revealed that the effects of GPx on ganoderic acid synthesis
      via ROS are regulated by the cytosolic Ca(2+) content. Taken together, these
      findings indicate that ROS have a complex influence on growth, development and
      secondary metabolism in fungi and that GPx serves an important function. The
      present study provides an excellent framework to identify GPx functions and
      highlights a role for this enzyme in ROS regulation. 

PMID- 26216673
TI  - Implications on clinical management of the small renal mass in patients 80 years
      of age and older based on a retrospective review of the SEER database.
AB  - PURPOSE: Incidental detection of small renal masses has increased in recent years
      with increased use of various imaging modalities, and a substantial number of
      diagnoses are made in the elderly population. Minimally invasive surgical
      procedures have previously been established as options with excellent long-term
      oncological results, but surveillance strategies have more recently been
      introduced as alternatives for surgical intervention. This study reviews the
      outcomes for elderly patients treated with observation or surgery for small renal
      masses in order to better elucidate optimal management strategies. METHODS: A
      total of 4647 patients from the SEER database met criteria for inclusion in this
      study. Cumulative incidences of RCC-specific mortality and non-RCC-related
      mortality were estimated, and frequency distributions by tumor size and surgical
      status were calculated. RESULTS: No difference in RCC-related mortality was
      observed among all treatment groups, including surveillance, for tumors 1-30 mm
      in size. RCC-related mortality was significantly lower for surgically treated
      patients for all other tumor size groups. Mortality unrelated to RCC was
      significantly higher in patients undergoing surveillance compared to those
      undergoing surgical intervention for tumor sizes 1-30 or 1-40 mm. CONCLUSIONS: A
      small renal mass in patients of 80+ years of age is best defined as up to 3 cm in
      size. For these patients, observation appears be a valid, if not preferential
      strategy. Patients 80+ years of age with renal masses greater than 3 cm still
      appear to benefit from surgical intervention.

PMID- 26216674
TI  - Tubular proteinuria is the dominant type of proteinuria in an elderly community
      population in China.
AB  - PURPOSE: To explore the types of proteinuria in the elderly population in China.
      METHODS: Seven hundred and fourteen elderly people (>= 60 years old) from
      Tianjin, China, were selected for the study. The albumin-to-creatinine ratio and
      alpha1-microglobulin-to-creatinine ratio from morning urine samples were used as
      indicators of proteinuria. The prevalence of proteinuria was evaluated and the
      proportion of three different types of proteinuria (mixed, glomerular, and
      tubular) was assessed in the subjects by analyzing these indicators. RESULTS: Of
      the 714 subjects, 29.13 % had elevated ACR and 46.36 % had elevated MCR. The
      proportion of subjects with either elevated ACR or MCR was 53.78 %. The
      correlation between MCR and ACR was moderate (r = 0.58, R (2) = 0.34, P < 0.001).
      Overall, tubular proteinuria was dominant (45.83 %), followed by mixed glomerular
      and tubular proteinuria (35.68 %), and significantly higher than glomerular
      proteinuria. A diet high in salt was the independent risk factor for tubular
      proteinuria; physical activity was the independent risk factor for glomerular
      proteinuria. The risk of glomerular proteinuria was lower in males than in
      females, but the risk of tubular proteinuria was higher in males. CONCLUSIONS:
      The prevalence of tubular proteinuria was higher than that of glomerular
      proteinuria, and the risk factors are different, in the elderly in China;
      therefore, tubular damage markers should get more attention in the overall
      population.

PMID- 26216676
TI  - A rare case: spontaneous bilateral synchronous testicular torsion.

PMID- 26216677
TI  - Orofacial reflex myocloni. Definition, relation to epilepsy syndromes,
      nosological and prognosis significance. A focused review.
AB  - PURPOSE: There is increasing awareness that reflex epileptic mechanisms provide
      unique insight into ictogenesis in human epilepsies. Among the complex triggers
      of seizures, this review considers orofacial reflex myocloni (ORM) from the
      aspects of history and delineation, clinical and electroencephalographic
      presentation, syndromatic relations, prevalence, mechanisms of ictogenesis and
      nosological implications, treatment and prognosis. METHODS: We reviewed all
      published articles and case reports on ORM in order to clarify clinical and
      electroencephalographic findings, treatment and outcome. RESULTS: ORM, besides
      Reading Epilepsy (RE), is closely related to idiopathic generalized epilepsies
      especially Juvenile Myoclonic Epilepsy (JME) where hyperexcitability of the
      network supporting linguistic communication seems to provide the precondition for
      eliciting reflex myocloni in the perioral muscles active in the precipitating
      task. CONCLUSION: The conclusions on ictogenesis derived from ORM support the
      concept of both, RE and JME, as system disorders of the brain.

PMID- 26216675
TI  - Tamoxifen is a potent antioxidant modulator for sperm quality in patients with
      idiopathic oligoasthenospermia.
AB  - OBJECTIVE: To explore the new mechanisms of tamoxifen (TAM) in the treatment for
      patients with idiopathic oligoasthenospermia-antioxidation. METHODS: In a
      prospective, randomized, controlled clinical trial, 120 cases of idiopathic
      oligoasthenospermia were enrolled and randomly assigned to the indomethacin group
      (n = 60) treated with indomethacin (25 mg, bid) and TAM group (n = 60) treated
      with TAM (10 mg, bid) for 3 months. Before and after treatment, we evaluated
      semen parameters, serum malondialdehyde (MDA) and total antioxidant capacity
      (TAC), seminal plasma MDA and TAC, spermatozoa intracellular reactive oxygen
      species (ROS), sperm succinate dehydrogenase (SDH) activity, sperm mitochondrial
      membrane potential (MMP), and sperm adenosine triphosphate (ATP) content. The
      independent t test and one-way repeated measures analysis of variance were used
      to compare the variables between and within two groups. RESULTS: In the
      indomethacin group, the percentage of progressive motile sperms, total motility,
      sperm MMP, and ATP content were increased significantly after 3-month treatment
      (P < 0.05). In the TAM group, total sperm count, sperm concentration, the
      percentage of progressive motile sperms, total motility, serum and seminal plasma
      TAC, sperm MMP, and ATP content were significantly improved or increased (P <
      0.05), while spermatozoa intracellular ROS was significantly decreased (P <
      0.05). Compared to the indomethacin group, TAM treatment showed better
      improvement in total sperm count, sperm concentration, serum TAC, seminal plasma
      TAC, spermatozoa intracellular ROS, and sperm SDH activity. CONCLUSIONS: TAM
      treatment can significantly improve sperm quality, which is achieved through
      alleviating oxidative stress, improving sperm mitochondrial functionality, and
      subsequently increasing sperm motility.

PMID- 26216678
TI  - Reduction of epileptiform activity through local valproate-implants in a rat
      neocortical epilepsy model.
AB  - PURPOSE: Pharmacotherapy of epilepsies is limited due to low concentrations at
      epileptogenic foci, side effects of high systemic doses and that some potentially
      efficient substances do not pass the blood-brain barrier. To overcome these
      limitations, we tested the efficacy of local valproate (VPA)-containing polymer
      implants in a model of necocortical injected tetanus toxin (TeT) in the rat.
      METHODS: Tetanus toxin was injected intracortically and cobalt (II) chloride
      (CoCl2) was applied on the cortical surface. Video-electrocorticography
      recordings with intracortical electrodes were performed. VPA-containing polymers
      were implanted above the cortical focus. Antiepileptic effects were evaluated as
      reductions of epileptiform potentials (EPs) per hour in comparison to saline
      (NaCl)-containing polymer implants. RESULTS: Triple 50ng TeT injections plus
      CoCl2 application (20/10mg) showed consistent EPs. NaCl-implanted animals (n=6)
      showed a mean of 10.5EPs/h after the first week, the EP frequency increased to
      53.5EPs/h after the second week. VPA-implant animals (n=5) showed a reduction in
      EP frequency from 71.6 to 4.8EPs/h after the second week. The EP frequency after
      the second week was higher in the NaCl-implanted animals than in the VPA
      implanted (p=0.0303). The mean EPs/h increase in NaCl-implanted rats (+42.9EPs/h)
      was different (p=0.0087) from the mean EPs/h decrease in VPA-implanted rats (
      66.8EPs/h). CONCLUSION: Despite former publications no clear seizures could be
      reproduced but it was possible to establish focal EPs, which proved to be a
      reliable marker for epileptic activity. Local antiepileptic therapy with VPA has
      shown efficacy in decreasing EP frequency.

PMID- 26216679
TI  - Ketamine for the treatment of refractory status epilepticus.
AB  - Status epilepticus (SE) is an acute and severe illness of the central nervous
      system, and prolonged SE can lead to brain damage and even death. Ketamine is a
      noncompetitive antagonist of glutamatergic N-methyl-d-aspartate (NMDA) receptors.
      During prolonged seizures, the numbers and activities of GABA receptors gradually
      decrease; thus, the commonly used first-line and second-line antiepileptic drugs
      gradually fail. Simultaneously, the numbers and activities of glutamatergic NMDA
      receptors increase, often causing refractory status epilepticus (RSE) and thus
      providing the possibility of the use of ketamine to treat RSE. To improve the
      prognosis of SE, we present a narrative review of ketamine for the treatment of
      RSE in the extant literature. We draw the conclusion that ketamine appears to be
      effective and relatively safe for the control of multidrug-resistant RSE in
      children and adults.

PMID- 26216680
TI  - Bias in counseling of seizure patients following a transient impairment of
      consciousness: differential adherence to driver fitness guidelines.
AB  - PURPOSE: To determine primary care physicians' counseling as well as patients'
      driving behaviors following seizure and non-seizure events impairing
      consciousness in the community. METHODS: Patients attending a rapid-referral
      first seizure clinic were entered into the study if they were deemed medically
      unfit to drive according to national guidelines for driving licensure: had
      experienced a seizure or an unexplained episode of lost consciousness, and had a
      valid driver's license at the time of their index event. Risk of physician
      counseling in the community regarding driving cessation in the interval between
      initial primary care assessment and neurological consultation was examined as a
      primary outcome, and patient driving cessation was examined as a secondary
      outcome. RESULTS: 106 of 192 (55%) patients attending clinic met guideline
      criteria requiring driver fitness counseling in the primary care community, and
      89 patients (46%) were deemed medically-unfit to drive following the initial
      specialist consultation appointment. Among medically unfit driver cases, 73% were
      ultimately deemed to have experienced a seizure and 27% had experienced a non
      seizure event (e.g. syncope, PNES). Driver fitness counseling was more likely for
      seizure than non-seizure cases (unadjusted odds ratio: 4.14, p<0.05), as was
      patient driving cessation (5.10, p<0.05). CONCLUSION: Physician compliance with
      clinical practice guidelines appears strongly biased when counseling about
      driving following an episode of transient impairment in consciousness. The
      failure of the primary care medical community to apply driver fitness counseling
      equitably to both seizure and non-seizure drivers may have ramifications upon
      public safety or conversely disease-related quality-of-life.

PMID- 26216681
TI  - Epilepsy service provision in the National Health Service in England in 2012.
AB  - PURPOSE: The National Health Service in the United Kingdom compares favourably on
      many international measures of quality and cost-effectiveness. It has many
      centres of excellence for epilepsy care and in some areas is a world-leader.
      However, for over twenty years there have been concerns that the provision of
      good quality care is variable and in many areas major improvements are required.
      We report the results of the latest major survey into the quality of epilepsy
      care in the NHS. METHODS: Four target groups were sent questionnaires: acute
      hospital trusts, Clinical Commissioning Groups, local authorities and patients.
      Each questionnaire was specifically designed by Epilepsy Action after reviewing
      national guidance and quality standards. RESULTS: We present the key results of
      the survey and we discuss them in the context of the latest national guidelines,
      quality standards, the organisational structure of the NHS and the research
      literature. CONCLUSION: Although there are some examples of excellent services
      for people with epilepsy these results show that overall there has been little
      improvement in recent years and there continues to be significant geographical
      variability in quality with many areas offering sub-optimal care.

PMID- 26216682
TI  - Life after being diagnosed with psychogenic non-epileptic seizures (PNES): a
      South African perspective.
AB  - PURPOSE: The aim of the study was to explore the life experiences of South
      Africans who have been diagnosed as having PNES, with a focus on the aspects of
      the challenges which these individuals face, as well as the resources and coping
      strategies which are either made available to them or used by them in order to
      cope with PNES. METHODS: Ten semi-structured interviews were analysed by means of
      thematic analysis in order to explore themes around challenges and resources for
      those diagnosed with PNES. RESULTS: Various challenges were revealed by
      participants, as well as the resources used in order to deal with these
      challenges associated with being diagnosed with PNES. Some of the challenges
      included unexpected seizures, medical professionals, belief systems as well as
      family. However, resources to counteract these challenges were social support,
      medical professional as well as religion and spirituality. CONCLUSION: Although
      many challenges are encountered by those who are diagnosed with PNES, there are
      substantial resources from which these individuals draw in order to live
      fulfilling and satisfactory lives. As more information and research is
      accumulated, more resources may become available to benefit these individuals and
      allow them to recover from PNES. It should be noted that medical professionals
      were described as both a challenge as well as a resource for people with PNES.
      Therefore, we can conclude that these individuals are key in the experiences of
      those who have been diagnosed with PNES, and that they play a role on not only a
      diagnostic level, but also in providing support, information, as well as
      therapeutic benefits.

PMID- 26216683
TI  - Age at onset in patients with medically refractory temporal lobe epilepsy and
      mesial temporal sclerosis: impact on clinical manifestations and postsurgical
      outcome.
AB  - PURPOSE: To evaluate the demographic and clinical manifestations and postsurgical
      outcome of childhood-onset mesial temporal sclerosis and temporal lobe epilepsy
      (MTS-TLE) and establishing the potential differences as compared to the patients
      with adult-onset MTS-TLE. METHOD: In this retrospective study all patients with a
      clinical diagnosis of medically refractory TLE due to mesial temporal sclerosis,
      who underwent epilepsy surgery at Jefferson comprehensive epilepsy center, were
      recruited. Patients were prospectively registered in a database from 1986 through
      2014. Postsurgical outcome was classified into two groups; seizure-free or
      relapsed. Clinical manifestations and outcome were compared between patients with
      childhood-onset MTS-TLE (i.e., age at onset of the first afebrile habitual
      seizure below 10 years) and those with adult-onset MTS-TLE (i.e., age at onset of
      the first afebrile habitual seizure 20 years or above). RESULTS: One hundred and
      twelve patients had childhood-onset MTS-TLE and 76 had adult-onset MTS-TLE.
      Demographic, clinical, EEG and MRI characteristics of these two groups were
      similar. Postoperative outcome was not statistically different between these two
      groups of patients (P=0.9). CONCLUSION: Temporal lobe epilepsy due to mesial
      temporal sclerosis is a common cause of epilepsy that can start from early
      childhood to late adulthood. The etiology of MTS-TLE may be different in various
      age groups, but it seems that when mesial temporal sclerosis is the pathological
      substrate of TLE, clinical manifestations and response to surgical treatment of
      patients are very similar in patients with childhood-onset MTS-TLE compared to
      those with adult-onset disease.

PMID- 26216684
TI  - Validation of a phone app for epilepsy diagnosis in India and Nepal.
AB  - PURPOSE: Untreated epilepsy is a major global public health problem with more
      than 20 million people not being treated for an easily treatable disease. In part
      this is due to a lack of trained doctors. There are many more non-medical health
      workers than doctors and they could have an important role in diagnosis and
      treatment of epilepsy if they had some tools. We have previously described such a
      tool to distinguish epileptic episodes from other causes of altered consciousness
      and here present its validation in three new populations. METHODS: The tool was
      presented as a phone app where the answers to 11 questions provided a probability
      score which indicated whether episodes might be due to epilepsy or not. It was
      applied either by non-medical volunteers, health workers, or inexperienced
      doctors to 132 patients in three separate populations in India and Nepal and
      compared with the "gold standard" diagnosis of a neurologist with expertise in
      epilepsy. RESULTS: There was good agreement between the app score and the
      neurologists' diagnoses (weighted kappa=75.3%). An app score of 90 or greater had
      a sensitivity of 88% and a specificity of 100% for diagnosing epilepsy. The app
      was easy to use with little training and took about 5min to administer.
      CONCLUSION: A tool presented as a phone app can be used by non-medical health
      workers to identify episodes as epileptic or not with good accuracy. It needs to
      be evaluated more widely but has the potential to play a part in reducing the
      epilepsy treatment gap.

PMID- 26216685
TI  - Cognitive outcome two years after frontal lobe resection for epilepsy--a
      prospective longitudinal study.
AB  - PURPOSE: To investigate cognitive outcomes after frontal lobe resection (FLR) for
      epilepsy in a consecutive single centre series. METHODS: Neuropsychological
      examinations were performed prior to and two years (mean test interval 2.5 years)
      after surgery in 30 consecutive patients who underwent FLR. Cognitive outcome was
      evaluated with particular consideration to the site of surgery (lateral,
      premotor/SMA [supplementary motor area], mesial/orbital). Cognitive domains
      assessed were speed, language, memory, attention, executive functions and
      intelligence. 25 healthy controls were assessed at corresponding time points
      (mean test interval 3.0 years). Analyses were made both at group and individual
      levels. RESULTS: At baseline the patients performed below controls in variables
      depending on speed, executive functions, global and verbal intelligence. Two
      years after surgery, the analyses at the subgroup level indicated that the
      lateral resection group had less improvement than the controls in global
      intelligence, FSIQ (p=.037). However, at the individual level, the majority of
      the change scores (74-100%) were classified as within the normal range for all
      but one variable. The exception was the variable "Comprehension" (measuring
      verbal reasoning ability) with reliable declines in 44% (8/18) of the patients.
      This pattern of decline was observed in the lateral (4/7 patients) and
      premotor/SMA (4/7 patients) resection groups. Seizure outcome and side of surgery
      did not influence these results. CONCLUSION: The main finding was cognitive
      stability at group level two years after FLR. A reliable decline in verbal
      reasoning ability was rather common at an individual level, but only in the
      lateral and premotor/SMA resection groups. The lateral resection group also had
      less improvement than the controls in global intelligence.

PMID- 26216686
TI  - Treatment of immune-mediated temporal lobe epilepsy with GAD antibodies.
AB  - PURPOSE: Temporal lobe epilepsy with antibodies (abs) against the glutamic acid
      decarboxylase 65 isoform (GAD-TLE) is known as an immune-mediated neurological
      syndrome. Here we evaluate the therapy response to various immunotherapies and
      epilepsy surgery in this syndrome. METHOD: All patients with GAD-TLE and follow
      up data and stored serum and CSF samples, identified and treated at the Bonn
      centre from 2002 to 2010, were studied retrospectively. Seizure freedom for >=1
      year and reduction of >=50%, i.e. therapy response, were assessed. GAD-ab titres
      and neuropsychological performances were documented prior and after individual
      interventions. RESULTS: Thirteen patients with GAD-TLE were identified with the
      following seizure responses: corticosteroids (5 responders out of 11 treated
      patients); i.v. immunoglobulins (1/5), apheresis therapy (1/8); and natalizumab
      (1/1), selective amygdala-hippocampectomy (2/3). None of the patients achieved
      sustained seizure freedom apart from one patient. This patient was on
      antiepileptic drug treatment after discontinuation of immunotherapy. CONCLUSION:
      The seizure response to immunotherapies in patients with GAD-TLE was poor.
      Corticosteroids were the most effective regarding seizure response. Especially
      the poor effects of apheresis therapies support the idea that GAD-abs are not
      directly pathogenic. None of three patients was seizure-free after temporal lobe
      surgery suggesting that GAD-TLE patients respond worse than others to this type
      of intervention. Our results reflect the chronic course of the disease with low
      likelihood for patients with GAD-TLE to attain long-term seizure freedom.

PMID- 26216687
TI  - Association study between polymorphisms in the CACNA1A, CACNA1C, and CACNA1H
      genes and drug-resistant epilepsy in the Chinese Han population.
AB  - PURPOSE: As important ion channels of the central nervous system, calcium
      channels not only take part in epileptogenesis but also act as the targets of
      commonly used antiepileptic drugs (AEDs). Thus, this study aimed to provide the
      first investigation of the association between CACNA1A, CACNA1C, and CACNA1H
      single nucleotide polymorphisms (SNPs) and AED resistance in the Chinese Han
      population. METHODS: We performed genotyping of tagging single nucleotide
      polymorphisms (tagSNPs) of CACNA1A, 1C and 1H in 480 Chinese epilepsy patients
      (288 drug-responsive and 192 drug-resistant patients). The Illumina GoldenGate
      BeadArray assay was used to detect the genotypes of all of the patients. A total
      of 15 SNPs were selected based on the HapMap database. The genotype distributions
      in drug-responsive and drug-resistant patients were compared, and the haplotype
      frequencies of each gene were calculated. RESULTS: None of the 15 tagSNPs alleles
      were found to be associated with drug-resistant epilepsy. However, the frequency
      of the TAGAA haplotype in CACNA1A was significantly higher in drug-resistant
      patients than in drug-responsive patients after the correction of multiple
      comparisons with Bonferroni's method (TAGAA 13.3% vs. 7.1%, OR=2.129 [1.373
      3.299], P=0.00059<0.05/10). CONCLUSIONS: This study revealed no association
      between the 15 tagSNPs of CACNA1A, 1C, and 1H and drug efficacy in the Chinese
      Han population. The TAGAA haplotype of CACNA1A may be a risk factor for AED
      resistance.

PMID- 26216688
TI  - Improvement of language development after successful hemispherotomy.
AB  - PURPOSE: To investigate language development after functional hemispherotomy and
      to evaluate prognostic factors for (un-)favourable outcomes. METHODS: Children
      and adolescents who had vertical perithalamic hemispherotomy at the Medical
      University Wien (MUW) paediatric epilepsy centre were identified from a
      prospectively maintained database. Inclusion criteria were: complete clinical,
      neurophysiological and neuropsychological data, seizure freedom and a minimum
      follow-up of 12 months after surgery. The language quotients (LQ) prior to
      surgery and at last follow-up were calculated for each child. In addition,
      associations between pre- to post-surgical changes in LQ and the following
      variables were examined: age at epilepsy-onset, age at surgery and duration of
      epilepsy prior to surgery, aetiology, side of surgery, interictal EEG including
      sleep organization before and 12 months after surgery and antiepileptic-drug
      (AED) withdrawal state at last follow-up. Analyses were carried out in SPSS
      version 20.0 (SPSS Inc., Chicago, IL, USA). Nonparametric Wilcoxon and chi-square
      tests were applied, as required. RESULTS: Data from 28 children (14 female) were
      analyzed. The median age at epilepsy surgery was 64.5 months. The median follow
      up after surgery was 3.0 years (+/-2.6 years, range 12 months to 12 years).
      Significant gains in LQs at last follow-up were found in 31% of the children
      (p=0.008). Short disease duration prior to surgery, acquired pathology, lack of
      epileptiform EEG discharges in the contralateral hemisphere and/or normalization
      of EEG sleep patterns after surgery, and successful AED withdrawal were linked to
      favourable language outcomes. CONCLUSION: Successful and early hemispherotomy
      results in improvement of language function in the intact hemisphere.

PMID- 26216689
TI  - A long-term patient perspective after hemispherotomy--a population based study.
AB  - PURPOSE: Explore the long-term life situation for Swedish hemispherotomy patients
      reporting not only seizure outcome but also patients' perspectives on function,
      quality of life (QoL) and satisfaction with the surgery. METHODS: This population
      based study uses prospectively collected data from the Swedish National Epilepsy
      Surgery Register. An independent researcher interviewed patients or parents,
      using two patient oriented questionnaires. RESULTS: Twenty-nine patients
      underwent hemispherotomy in Sweden after 1995 and had a five- or ten-year follow
      up. At the 2-year follow-up 55% (16/29) were seizure-free since surgery, and
      11/29 (38%) were seizure-free at the long term follow up. Twenty-six (90%)
      participated in this study. Median time to interview was 13.5 years; 9/26 (35%)
      were seizure-free then; 23% were off antiepileptic medication. In those not
      seizure-free, seizures were considered mild or moderate; 11% attended mainstream
      school and 3/12 adults lived independently. Most parents both of seizure-free and
      non seizure-free patients reported QoL and general health to be very good/good;
      73% were satisfied/very satisfied with the hemispherotomy. CONCLUSION: In this
      series there were more long-term recurrences than previously reported. This might
      be related to the lower level of function of this cohort and higher percentage of
      developmental aetiologies compared to other series. However, most hemispherotomy
      patients have a good QoL in the long run and feel that the operation was
      worthwhile, even when it did not stop seizures. The majority had persisting
      impairments. Proxies were not very concerned about seizures, indicating that
      reduction in seizure frequency and/or severity may be an important gain with
      hemispherotomy.

PMID- 26216690
TI  - Long-term follow-up after epilepsy surgery in infancy and early childhood--a
      prospective population based observational study.
AB  - PURPOSE: To describe 2-year and long-term outcomes (five or ten years) after
      resective epilepsy surgery in children operated before the age of four years.
      METHODS: This prospective, population based, longitudinal study is based on data
      from the Swedish National Epilepsy Surgery Register 1995-2010. The following
      variables were analysed: seizure frequency, antiepileptic drug treatment (AED),
      neurological deficits, type of operation, histopathological diagnosis and
      perioperative complications. RESULTS: During the study period 47 children under
      four years had resective surgery. A majority had seizure onset within the first
      year of life, and the median age at surgery was two years and one month. Two
      thirds had neurodevelopmental abnormalities. Temporal lobe resection, frontal
      lobe resection and hemispherotomy predominated. A majority had malformations of
      cortical development. There was one major perioperative complication. At the 2
      year follow-up, 21/47 children (45%) were seizure free, eight of whom were off
      medication. At the long-term follow-up, 16/32 (50%) were seizure-free and 11 of
      them off medication. Another ten (31%) had >=75% reduction in seizure frequency.
      Fourteen children (44%) had sustained seizure freedom from surgery to the long
      term follow-up. CONCLUSION: This is the first prospective, population based,
      longitudinal study to show that a favourable seizure outcome is achievable in a
      majority of infants and young children undergoing resective epilepsy surgery and
      that the improvements are consistent over time. Many can also stop taking AEDs.
      The findings emphasise the importance of early referral to epilepsy surgery
      evaluation in cases of medically intractable epilepsy in infants and young
      children.

PMID- 26216691
TI  - Diagnostic yield of five minutes compared to three minutes hyperventilation
      during electroencephalography.
AB  - PURPOSE: To investigate whether hyperventilation (HV) for 5min increases the
      diagnostic yield of electroencephalography (EEG) compared to 3min HV. METHODS:
      data were evaluated from 1084 consecutive patients, from three European centres,
      referred to EEG on suspicion of epilepsy. Seizures and interictal EEG
      abnormalities precipitated during the first 3min and during the last 2min of the
      HV period (totally 5min) were determined. RESULTS: Eight hundred seventy-seven
      patients (81%) completed 5min HV. Seizures were precipitated during the first
      3min of HV in 21 patients, and during the last 2min in four more patients.
      Interictal EEG abnormalities were precipitated in the first 3min of HV in 16
      patients, and during the last 2min in 7 more patients. Psychogenic nonepileptic
      seizures occurred in eight patients during the first 3min of HV and in two more
      patients during the last 2min. No adverse events occurred during the last 2min of
      HV, but eight patients (1%) stopped HV during the last 2min because they were not
      able to hyperventilate further. CONCLUSION: 16% of seizures and 30% of interictal
      EEG abnormalities triggered by HV occurred during the last 2min of HV, suggesting
      the clinical usefulness of prolonged hyperventilation for 5min. The vast majority
      of patients (99%) who are able to hyperventilate for 3min can complete 5min HV,
      without additional adverse events.

PMID- 26216692
TI  - Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified
      single antiepileptic medications in an open-label study of adults with partial
      onset seizures.
AB  - PURPOSE: To assess efficacy/tolerability of ezogabine (EZG)/retigabine (RTG) in
      combination with specified monotherapy antiepileptic drug (AED) treatments in
      adults with uncontrolled partial-onset seizures using a flexible dosing regimen.
      METHODS: NCT01227902 was an open-label, uncontrolled study of flexibly dosed
      EZG/RTG. Adults with partial-onset seizures must have been taking either
      carbamazepine/oxcarbazepine (CBZ/OXC), lamotrigine (LTG), levetiracetam (LEV), or
      valproic acid (VPA). The study comprised a screening/baseline phase, a 4-week
      titration phase (initiation on 150mg/day [50mg three times daily (TID)] with
      weekly increases of 150mg/day [50mg TID] over 4 weeks to 600mg/day), and a
      flexible dose evaluation (FDE) phase (optional weekly dose changes of 50
      150mg/day, to an optimal daily dosage [300-1200mg/day]). The primary efficacy
      endpoint was percentage of patients experiencing a >=50% reduction from baseline
      in partial seizure frequency (responder rate) during the treatment phase
      (titration and FDE phases). Safety and tolerability were also assessed. RESULTS:
      Patients (N=203) were enrolled and received >=1 dose of EZG/RTG. The dose of
      EZG/RTG prescribed most frequently during the treatment phase was 600mg/day for
      all AED groups. Responder rates during the treatment phase were: 40.0% (CBZ/OXC),
      32.0% (LTG), 50.0% (LEV), and 56.9% (VPA). Treatment-emergent adverse events
      occurred in 82% (CBZ/OXC), 76% (LTG), 73% (LEV), and 67% (VPA) of patients; most
      were of mild-to-moderate intensity. CONCLUSIONS: EZG/RTG was effective as
      adjunctive therapy to CBZ/OXC, LTG, LEV, and VPA, using a flexible dosing
      regimen, in adults with partial-onset seizures; safety and tolerability were
      consistent with that previously observed.

PMID- 26216693
TI  - Abnormal motor cortex plasticity in juvenile myoclonic epilepsy.
AB  - PURPOSE: Abnormal cortical plasticity has been hypothesized to play a crucial
      role in the pathogenesis of juvenile myoclonic epilepsy (JME). To study the motor
      cortical plasticity we used paired associative stimulation (PAS). When a
      repetitive electrical stimulus to the median nerve is paired with a transcranial
      magnetic stimulus (TMS) pulse over the controlateral motor cortex with at an
      interstimulus interval (ISI) of 21.5-25ms, a long term potentiation (LTP)-like
      synaptic plasticity is induced in the corticospinal system. Aim of this study was
      to investigate the motor cortex LTP-like synaptic plasticity by means of PAS in
      patients with JME. METHODS: Twelve adult patients with JME were compared with 13
      healthy subjects of similar age and sex. PAS consisted of 180 electrical stimuli
      of the right median nerve paired with a single TMS over the hotspot of right
      abductor pollicis brevis (APB) at an ISI of 25ms (PAS25). We measured motor
      evoked potentials (MEPs) before and after each intervention for up to 30min.
      RESULTS: In healthy subjects the PAS25 protocol was followed by a significant
      increase of the MEP amplitude (p<0.001). On the contrary, in patients with JME,
      the MEP amplitude did not change. CONCLUSION: Defective motor cortex plasticity
      is likely involved in the pathogenesis of JME.

PMID- 26216694
TI  - Factors associated with increased felt stigma among individuals with epilepsy.
AB  - PURPOSE: The aim of the study is to determine whether certain demographic,
      clinical, and psychosocial traits are associated with higher levels of felt
      stigma among persons with epilepsy (PWE) patients followed at a level 4 epilepsy
      center. METHODS: We performed a direct survey of 182 consenting patients that
      included the Epilepsy Stigma Scale. RESULTS: On univariate analysis, higher
      levels of perceived stigma were associated with age, marital status, race,
      driving, work status, seizure etiology, Quality of Life in Epilepsy-10 (QOLIE-10)
      scores, and health literacy. Among coping reactions, the use of denial,
      behavioral disengagement and venting were also associated with higher degrees of
      felt stigma. Using multiple linear regression, being single, poorer QOLIE-10
      scores, difficulties understanding written information, and the use of behavioral
      disengagement were independently associated with poorer scores on the Epilepsy
      Stigma Scale. CONCLUSION: Our study paints a compelling profile of a PWE who has
      greater perceived stigma. Programs that increase the level of social support,
      improve health literacy, and enhance quality of life may also help decrease the
      amount of felt stigma among PWE.

PMID- 26216695
TI  - Deaths in children with epilepsies: a UK-wide study.
AB  - PURPOSE: This UK-wide review of deaths in children with epilepsies was undertaken
      to ascertain any demographic, clinical, organisational, or management factors
      associated with the deaths, and to determine the extent to which any of these may
      have deviated from nationally agreed best practice. METHOD: Paediatricians across
      the UK were asked to notify any deaths in children with epilepsies over a 10
      month period. Hospital and community case notes were reviewed by pairs of case
      assessors using a structured assessment tool combining holistic and criterion
      based approaches. RESULTS: Of 46 deaths notified, case notes were obtained on 33.
      The majority of children had associated developmental impairments. The majority
      (24), died of an associated co-morbidity rather than of epilepsy. Seven died of
      convulsive status epilepticus and seven as sudden unexpected deaths in epilepsy.
      Twenty four percent of deaths were judged to be preventable; potentially
      modifiable factors included fragmentation of care, support for families, and
      recognition of and response to acute illness in the child, including the
      appropriate management of prolonged seizures. CONCLUSIONS: Although this audit
      has demonstrated significant improvements in quality of care when compared with
      the last national audit of epilepsy deaths in 2002, further improvement is still
      required.

PMID- 26216696
TI  - Probability of detection of clinical seizures using heart rate changes.
AB  - PURPOSE: Heart rate-based seizure detection is a viable complement or alternative
      to ECoG/EEG. This study investigates the role of various biological factors on
      the probability of clinical seizure detection using heart rate. METHODS:
      Regression models were applied to 266 clinical seizures recorded from 72 subjects
      to investigate if factors such as age, gender, years with epilepsy, etiology,
      seizure site origin, seizure class, and data collection centers, among others,
      shape the probability of EKG-based seizure detection. RESULTS: Clinical seizure
      detection probability based on heart rate changes, is significantly (p<0.001)
      shaped by patients' age and gender, seizure class, and years with epilepsy. The
      probability of detecting clinical seizures (>0.8 in the majority of subjects)
      using heart rate is highest for complex partial seizures, increases with a
      patient's years with epilepsy, is lower for females than for males and is
      unrelated to the side of hemisphere origin. CONCLUSION: Clinical seizure
      detection probability using heart rate is multi-factorially dependent and
      sufficiently high (>0.8) in most cases to be clinically useful. Knowledge of the
      role that these factors play in shaping said probability will enhance its
      applicability and usefulness. Heart rate is a reliable and practical signal for
      extra-cerebral detection of clinical seizures originating from or spreading to
      central autonomic network structures.

PMID- 26216697
TI  - Extrafrontal structural changes in juvenile myoclonic epilepsy: a topographic
      analysis of combined structural and microstructural brain imaging.
AB  - PURPOSE: An increasing amount of evidence has demonstrated that juvenile
      myoclonic epilepsy (JME) is associated with structural abnormalities in not only
      the thalamofrontal system but its adjacent regions such as temporal or parieto
      occipital areas. The goal of this study was to systematically characterize
      morphological changes and the subsequent pathophysiological implications in JME
      patients using the combined structural and diffusion tensor MRI analysis.
      METHODS: Comparisons of white matter (WM) water diffusivity and gray matter (GM)
      cortical thickness were analyzed with tract-based spatial statistics (TBSS) and a
      Constrained Laplacian-based Anatomic Segmentation with Proximity (CLASP)
      algorithm, respectively. Additionally, volumes of the bilateral thalami and
      hippocampi were obtained using manual volumetry (MV). RESULTS: Compared with 22
      normal controls, 18 patients with JME exhibited WM alterations in the antero
      superior corona radiata, corpus callosum, both centro-parietal regions, and the
      left temporal lobe. JME patients also had reduced GM thickness (right paracentral
      lobule, precuneus, dorsolateral parietal and inferior temporal cortex; left
      dorsolateral frontal and anterior temporal areas). Furthermore, MV analyses
      revealed a significant volume reduction in the bilateral thalami and hippocampi.
      CONCLUSIONS: In addition to structural changes in the thalamofrontal system,
      there was a conspicuous alteration of WM diffusivity in widespread extra-frontal
      areas and an associated decreased GM thickness in temporoparietal regions,
      including a significant reduction of hippocampal volume. These findings suggest
      that the pathophysiology of JME may be not confined to the thalamofrontal circuit
      but may also involve extensive areas of the extra-frontal network which
      encompasses temporo-parietal regions.

PMID- 26216698
TI  - Variability in clinical assessment of neuroimaging in temporal lobe epilepsy.
AB  - PURPOSE: Neuroimaging is critical in deciding candidacy for epilepsy surgery.
      Currently imaging is primarily assessed qualitatively, which may affect patient
      selection and outcomes. METHOD: The epilepsy surgery database at MGH was reviewed
      for temporal lobectomy patients from the last 10 years. Radiology reports for MRI
      and FDG-PET were compared to the epilepsy conference consensus. First, specific
      findings of ipsi/contra hippocampal atrophy and T2 signal changes were directly
      compared. Next the overall impression of presence of hippocampal sclerosis (HS)
      for MRI and temporal hypometabolism for PET was used for sensitivity/specificity
      analysis. To assess predictive power of imaging findings logistic regression was
      used. RESULTS: 104 subjects were identified. 70% of subjects were ILAE class I at
      1-year. Radiology reports and the conference consensus differed in 31% of FDG-PET
      studies and 41% of MRIs. For PET most disagreement (50%) stemmed for discrepancy
      regarding contralateral temporal hypometabolism. For MRI discrepancy in
      ipsilateral hippocampal atrophy/T2 signal accounted for 59% of disagreements.
      When overall impression of the image was used the overall reliability between
      groups was high with only MRI sensitivity to detect HS (0.75 radiology, 0.91
      conference, p=0.02) was significantly different between groups. On logistic
      regression MRI was a significant predictor of HS, but still 36% of patients with
      normal MRI as read by both groups had HS on pathology. CONCLUSION: Despite some
      difference in specific radiologic findings, overall accuracy for MRI and PET is
      similar in clinical practice between radiology and conference; nonetheless there
      are still cases of hippocampal pathology not detected by standard imaging
      methods.

PMID- 26216699
TI  - Will weight loss become a future treatment of hepatocellular adenoma in obese
      patients?
AB  - BACKGROUND & AIMS: Although hepatocellular adenoma (HCA) is more frequently
      observed in obese patients, however, the effect of weight loss as a therapeutic
      option was never studied. METHODS: In this rapid communication we described our
      non-surgical management of large HCA (>5 cm) encountered in patients with morbid
      obesity. Non-surgical management consisted mainly of oral contraception
      withdrawal and weight loss, which was the only option in two patients. All
      demographics, radiological and histological data were studied. Patients were
      followed regularly every 6 months. RESULTS: Between 2004 and 2013, 116 patients
      presented with HCA and 15 with morbid obesity (13%) were studied. Five men
      underwent surgery and females were either operated (period before 2010; n = 5) or
      proposed to non-surgical management (period after 2010; n = 5).Weight loss was
      advocated to all females, including four with residual HCA after resection and to
      non-operated patients, including two with haemorrhagic HCA. Four (40%) females
      showed significant weight loss. In resected patients, weight loss allowed
      stability (n = 1) or slight regression (n = 1) of residual HCA. In the two
      patients treated only by weight loss, significant decrease was observed in the
      weight with significant decrease (>50%) in the size and number of HCA to a non
      surgical size (<5 cm). Severe morbidity was 40% in operated patients and 0% in
      non-operated patients. After a follow-up period of 38 months (18-60), no
      complication or degeneration was encountered in the non-operated group.
      CONCLUSION: Like oral contraception, weight loss should be considered as the
      first therapeutic option in the management of HCA in obese patients.

PMID- 26216700
TI  - Associations between oral disorders and the quality of life of older adults in
      Brazil.
AB  - AIM: To evaluate the effect of oral disorders on the quality of life of older
      adults. METHODS: A cross-sectional study of older adults (aged >= 60 years) who
      reside in a small Brazilian city was carried out. Trained and calibrated
      academics and dentists collected the data. The analyses carried out were
      descriptive, univariate and multiple through logistic regression using pasw
      Statistics 18.0 software. RESULTS: A total of 351 older adults were included in
      the study. The majority of older adults did not express impacts as a result of
      oral disorders. The physical domain of quality of life was compromises more in
      older adults who had physical incapacities related to oral health (odds ratio
      3.62, 95% confidence interval 1.34-9.73). CONCLUSION: In general, among the older
      adults evaluated, it was found that both the overall score and the individual
      scores for the four domains of quality of life were influenced by one of the
      seven domains of the impacts of oral disorders.

PMID- 26216701
TI  - Synergistic Carbon Dioxide Capture and Conversion in Porous Materials.
AB  - Global climate change and excessive CO2 emissions have caused widespread public
      concern in recent years. Tremendous efforts have been made towards CO2 capture
      and conversion. This has led to the development of numerous porous materials as
      CO2 capture sorbents. Concurrently, the conversion of CO2 into value-added
      products by chemical methods has also been well-documented recently. However,
      realizing the attractive prospect of direct, in situ chemical conversion of
      captured CO2 into other chemicals remains a challenge. 

PMID- 26216702
TI  - Adverse drug reactions in a psychiatric department of tertiary care teaching
      hospital in India: Analysis of spontaneously reported cases.
AB  - The epidemiological data are limited for the spontaneous adverse drug reaction
      (ADR) reporting system in psychiatry and its comparison with intensive monitoring
      studies in terms of causative drugs, seriousness, preventability and drug
      interactions. This spontaneous ADR reporting study was carried out over a period
      of three years in the psychiatry department. We adopted WHO definition for an
      ADR, Naranjo's algorithm for causality, WHO-ADR terminology for the labeling of
      involved organ-system, International conference on harmonisation (ICH) E2A
      guidelines for seriousness, modified Schumock and Thornton's criteria for
      preventability and Medscape drug interaction checker for drug interactions. Two
      subgroup analyses were performed to find out the risk factors for the serious and
      preventable reactions. A total of 97 ADRs from 67 patients were included for
      analysis. The incidence of 'overall' and 'serious ADRs were 0.69% (95% CI: 0.54%,
      0.88%) and 0.18% (95% CI: 0.12-0.29%), respectively. The females experienced more
      ADRs than males. The most commonly reported ADR, incriminated pharmacology group
      and drug, were extrapyramidal movement disorders (22.68%), atypical
      antipsychotics (35.62%) and escitalopram (13.91%), respectively. One out of five
      and one out three reactions were considered as 'serious' and 'preventable',
      respectively. The drug interactions contributed in 34.02% reactions. The factors
      significantly associated with 'serious' reactions were typical antipsychotics
      [OR: 5.47 (1.68, 17.87)], central and peripheral nervous system disorders [OR:
      24.00 (5.12, 112.5)] and extrapyramidal reactions [OR: 14.03 (4.43, 44.43)]. The
      polypharmacy [OR: 5.85 (1.90, 18.03)] was significantly associated with
      'preventable' reactions. The spontaneous reporting system is efficient to detect
      serious reactions and preventable reactions. 

PMID- 26216703
TI  - Gilles de la Tourette syndrome in a cohort of deaf people.
AB  - We present six patients with Gilles de la Tourette syndrome (TS) who are also
      deaf. TS has been observed previously, but rarely reported in deaf people, and to
      date, so called "unusual" phenomenology has been highlighted. TS occurs almost
      worldwide and in all cultures, and the clinical phenomenology is virtually
      identical. In our cohort of deaf patients (we suggest another culture) with TS,
      the phenomenology is the same as in hearing people, and as in all other cultures,
      with classic motor and vocal/phonic tics, as well as associated phenomena
      including echo-phenomena, pali-phenomena and rarer copro-phenomena. When "words"
      related to these phenomenon (e.g. echolalia, palilalia, coprolalia or mental
      coprolalia) are elicited in deaf people, they occur usually in British Sign
      Language (BSL): the more "basic" vocal/phonic tics such as throat clearing are
      the same phenomenologically as in hearing TS people. In our case series, there
      was a genetic predisposition to TS in all cases. We would argue that TS in deaf
      people is the same as TS in hearing people and in other cultures, highlighting
      the biological nature of the disorder. 

PMID- 26216705
TI  - Assessment of Cerebral Blood Flow with Micro-Doppler Vascular Reduces the Risk of
      Ischemic Stroke During the Clipping of Intracranial Aneurysms.
AB  - OBJECTIVE: To analyze the impact of the introduction of Micro-Doppler vascular
      (MDV) as a method of cerebral blood flow analysis during microsurgical clipping
      of intracranial aneurysms to check the partial occlusion of the aneurysm and the
      occurrence of stenosis by comparing these results with those provided by the
      postoperative digital subtraction angiography (DSA) scan as well as the
      occurrence of ischemic infarction on the postoperative computed tomography (CT)
      images. PATIENTS AND METHODS: We reviewed retrospectively the last 50 patients
      operated on before the introduction of the MDV (group 1) compared with the first
      50 patients operated on using this technique (group 2). RESULTS: Nine (18%) of
      the 50 patients evaluated in the group 1 showed a new hypodensity in the
      postoperative CT images, whereas only 2 (4%) patients showed infarction in the
      group 2 (P = 0.02). In addition, in the group 1, 10 (20%) patients presented
      unexpected findings on DSA images (residual aneurysms, stenosis, and arterial
      occlusion), whereas in the group 2, those unexpected DSA findings were observed
      in only 3 (6%) patients (P = 0.023). CONCLUSION: MDV is an excellent method for
      cerebral blood flow assessment during the microsurgical clipping of intracranial
      aneurysms, reducing the unexpected angiographic results (residual aneurysms,
      stenosis, and arterial occlusion), as well as reducing the incidence of ischemic
      infarction on postoperative CT images, evidence of the positive impact of this
      method in the microsurgical treatment of intracranial aneurysms.

PMID- 26216707
TI  - Simultaneous quantitation and validation of method for the quality evaluation of
      Eucommiae cortex by HPLC/UV.
AB  - A new HPLC/UV method has been developed for the simultaneous quantitative
      determination of four major components in Eucommiae cortex, namely geniposidic
      acid (1), geniposide (2), pinoresinol di-O-beta-D-glucopyranoside (3), and
      liriodendrin (4). Simultaneous separations of these four components were achieved
      on a J'sphere ODS C(18) column (250 * 4.6 mm, 4 um). The elution was done using
      water with 0.1% phosphoric acid (A) and acetonitrile with 0.1% phosphoric acid
      (B) in a two-step elution of the mobile phase at a flow rate of 1.0 mL/min and a
      wavelength of 230 nm. The method was validated for linearity, recovery,
      precision, accuracy, stability and robustness. All calibration curves showed good
      linear regression (r(2) > 0.999) within the test ranges. This method showed good
      recovery and reproducibility for the quantification of these four components in
      85 species of Eucommiae cortex. The intra-day and inter-day precisions were lower
      than 0.53% (as a relative standard deviation, RSD) and accuracies between 93.00
      and 106.28% for all standards. The results indicate that the established HPLC/UV
      method is suitable for quantitation and quality evaluation of Eucommiae cortex.

PMID- 26216706
TI  - After 30 years of dissemination, have we achieved sustained practice change in
      motivational interviewing?
AB  - AIMS: Motivational interviewing (MI) is the most successfully disseminated
      evidence-based practice in the substance use disorder (SUD) treatment field. This
      systematic review considers two questions relevant to policymakers and service
      providers: (1) does training in MI achieve sustained practice change in
      clinicians delivering SUD treatment; and (2) do clinicians achieve a level of
      competence after training in MI that impacts upon client outcomes? METHODS: A
      systematic review was conducted and reported in line with the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, examining
      training outcomes for MI in the SUD treatment sector, and for clinicians working
      in a SUD treatment role. We determined a training method to have resulted in
      sustained practice change when over 75% of participants met beginning proficiency
      in MI spirit at a follow-up time-point. RESULTS: Of the 20 studies identified, 15
      measured training at a follow-up time-point using standard fidelity measures. The
      proportion of clinicians who reached beginning proficiency was either reported or
      calculated for 11 of these studies. Only two studies met our criterion of 75% of
      clinicians achieving beginning proficiency in MI spirit after training. Of the 20
      studies identified, two measured client substance use outcomes with mixed
      results. CONCLUSIONS: A broad range of training studies failed to achieve
      sustained practice change in MI according to our criteria. It is unlikely that
      75% of clinicians can achieve beginning proficiency in MI spirit after training
      unless competency is benchmarked and monitored and training is ongoing. The
      impact of training on client outcomes requires future examination.

PMID- 26216708
TI  - Pathways for degradation of plastic polymers floating in the marine environment.
AB  - Each year vast amounts of plastic are produced worldwide. When released to the
      environment, plastics accumulate, and plastic debris in the world's oceans is of
      particular environmental concern. More than 60% of all floating debris in the
      oceans is plastic and amounts are increasing each year. Plastic polymers in the
      marine environment are exposed to sunlight, oxidants and physical stress, and
      over time they weather and degrade. The degradation processes and products must
      be understood to detect and evaluate potential environmental hazards. Some
      attention has been drawn to additives and persistent organic pollutants that sorb
      to the plastic surface, but so far the chemicals generated by degradation of the
      plastic polymers themselves have not been well studied from an environmental
      perspective. In this paper we review available information about the degradation
      pathways and chemicals that are formed by degradation of the six plastic types
      that are most widely used in Europe. We extrapolate that information to likely
      pathways and possible degradation products under environmental conditions found
      on the oceans' surface. The potential degradation pathways and products depend on
      the polymer type. UV-radiation and oxygen are the most important factors that
      initiate degradation of polymers with a carbon-carbon backbone, leading to chain
      scission. Smaller polymer fragments formed by chain scission are more susceptible
      to biodegradation and therefore abiotic degradation is expected to precede
      biodegradation. When heteroatoms are present in the main chain of a polymer,
      degradation proceeds by photo-oxidation, hydrolysis, and biodegradation.
      Degradation of plastic polymers can lead to low molecular weight polymer
      fragments, like monomers and oligomers, and formation of new end groups,
      especially carboxylic acids. 

PMID- 26216709
TI  - Lessons learned from studies with the growth hormone receptor.
AB  - Findings related to GH's biological activities have continued to be a fascinating
      topic over the past decade. Below, I will review several items related to the
      actions of GH including the GH/GHR interaction, pegvisomant (a GH receptor
      antagonist), GHR gene disruptions in mice, and clinical consequences of human GHR
      gene mutations.

PMID- 26216710
TI  - Tumor infiltrating immune cells in gliomas and meningiomas.
AB  - Tumor-infiltrating immune cells are part of a complex microenvironment that
      promotes and/or regulates tumor development and growth. Depending on the type of
      cells and their functional interactions, immune cells may play a key role in
      suppressing the tumor or in providing support for tumor growth, with relevant
      effects on patient behavior. In recent years, important advances have been
      achieved in the characterization of immune cell infiltrates in central nervous
      system (CNS) tumors, but their role in tumorigenesis and patient behavior still
      remain poorly understood. Overall, these studies have shown significant but
      variable levels of infiltration of CNS tumors by macrophage/microglial cells
      (TAM) and to a less extent also lymphocytes (particularly T-cells and NK cells,
      and less frequently also B-cells). Of note, TAM infiltrate gliomas at moderate
      numbers where they frequently show an immune suppressive phenotype and functional
      behavior; in contrast, infiltration by TAM may be very pronounced in meningiomas,
      particularly in cases that carry isolated monosomy 22, where the immune
      infiltrates also contain greater numbers of cytotoxic T and NK-cells associated
      with an enhanced anti-tumoral immune response. In line with this, the presence of
      regulatory T cells, is usually limited to a small fraction of all meningiomas,
      while frequently found in gliomas. Despite these differences between gliomas and
      meningiomas, both tumors show heterogeneous levels of infiltration by immune
      cells with variable functionality. In this review we summarize current knowledge
      about tumor-infiltrating immune cells in the two most common types of CNS tumors
      gliomas and meningiomas-, as well as the role that such immune cells may play in
      the tumor microenvironment in controlling and/or promoting tumor development,
      growth and control. 

PMID- 26216711
TI  - Intranasal midazolam during presurgical epilepsy monitoring is well tolerated,
      delays seizure recurrence, and protects from generalized tonic-clonic seizures.
AB  - OBJECTIVE: To evaluate the tolerability and efficacy of the ictal and immediate
      postictal application of intranasal midazolam (in-MDZ) in adolescents and adults
      during video-electroencephalography (EEG) monitoring. METHODS: Medical records of
      all patients treated with in-MDZ between 2008 and 2014 were reviewed
      retrospectively. For each single patient, the time span until recurrence of
      seizures was analyzed after an index seizure with and without in-MDZ application.
      To prevent potential bias, we defined the first seizure with application of in
      MDZ as the in-MDZ index seizure. The control index seizure was the preceding,
      alternatively the next successive seizure without application of in-MDZ. RESULTS:
      In total, 75 epilepsy patients (mean age 34 +/- 14.7 years; 42 male, 33 female)
      were treated with in-MDZ (mean dose 5.1 mg). Adverse events were observed in four
      patients (5.3%), and no serious adverse events occurred. The median time after
      EEG seizure onset before administration of in-MDZ was 2.17 min (interquartile
      range [IQR] 03.82; range 0.13-15.0 min). Over the next 12 h after in-MDZ, the
      number of seizures was significantly lower (p = 0.031). The median seizure-free
      interval was significantly longer following treatment with in-MDZ (5.83 h; IQR
      6.83, range 0.4-23.87) than it was for those with no in-MDZ treatment (2.37 h;
      IQR 4.87, range 0.03-21.87; p = 0.015). Conversely, the likelihood of the patient
      developing a subsequent seizure was four times higher (odds ratio [OR] 4.33, 95%
      confidence interval [CI] 1.30-14.47) in the first hour and decreased gradually
      after 12 h (OR 1.5, 95% CI 1.06-2.12). The occurrence of generalized tonic-clonic
      seizures was lower in the in-MDZ group in the 24-h observation period (OR 4.67,
      95% CI 1.41-15.45; p = 0.009). SIGNIFICANCE: Ictal and immediate postictal
      administration of in-MDZ was well tolerated and not associated with serious
      adverse events. We demonstrated a significant reduction of subsequent seizures
      (all seizure types) for a 12 h period and of generalized tonic-clonic seizures
      for 24 h following in-MDZ.

PMID- 26216712
TI  - Stabilization of 4H hexagonal phase in gold nanoribbons.
AB  - Gold, silver, platinum and palladium typically crystallize with the face-centred
      cubic structure. Here we report the high-yield solution synthesis of gold
      nanoribbons in the 4H hexagonal polytype, a previously unreported metastable
      phase of gold. These gold nanoribbons undergo a phase transition from the
      original 4H hexagonal to face-centred cubic structure on ligand exchange under
      ambient conditions. Using monochromated electron energy-loss spectroscopy, the
      strong infrared plasmon absorption of single 4H gold nanoribbons is observed.
      Furthermore, the 4H hexagonal phases of silver, palladium and platinum can be
      readily stabilized through direct epitaxial growth of these metals on the 4H gold
      nanoribbon surface. Our findings may open up new strategies for the crystal phase
      controlled synthesis of advanced noble metal nanomaterials. 

PMID- 26216713
TI  - Biotin/Folate-decorated Human Serum Albumin Nanoparticles of Docetaxel:
      Comparison of Chemically Conjugated Nanostructures and Physically Loaded
      Nanoparticles for Targeting of Breast Cancer.
AB  - Docetaxel (DTX) is a widely used chemotherapeutic agent with very low water
      solubility. Conjugation of DTX to human serum albumin (HSA) is an effective way
      to increase its water solubility. Attachment of folic acid (FA) or biotin as
      targeting moieties to DTX-HSA conjugates may lead to active targeting and
      specific uptake by cancer cells with overexpressed FA or biotin receptors. In
      this study, FA or biotin molecules were attached to DTX-HSA conjugates by two
      different methods. In one method, FA or biotin molecules were attached to
      remaining NH2 residues of HSA in DTX-HSA conjugate by covalent bonds. In the
      second method, HSA-FA or HSA-biotin conjugates were synthesized separately and
      then combined by DTX-HSA conjugate in proper ratio to prepare nanoparticles
      containing DTX-HSA plus HSA-FA or HSA-biotin. Cell viability of different
      nanoparticle was evaluated on MDA-MB-231 (folate receptor positive), A549 (folate
      receptor negative), and 4T1 (biotin receptor positive) and showed superior
      cytotoxicity compared with free docetaxel (Taxotere). In vivo studies of DTX-HSA
      FA and DTX-HSA-biotin conjugates in BULB/c mice, tumorized by 4T1 cell line,
      showed the conjugates prepared in this study were more powerful in the reduction
      in tumor size and increasing the survival rate when compared to free docetaxel.

PMID- 26216714
TI  - Inhaled corticosteroids in chronic obstructive pulmonary disease: Some
      considerations.

PMID- 26216715
TI  - Long-term Outcome of Patients With Undiagnosed Pleural Effusion.
AB  - INTRODUCTION: The cause of exudative pleural effusion cannot be determined in
      some patients. The longterm outcomes of patients with undiagnosed pleural
      effusion were analyzed. METHODS: Patients with exudative pleural effusion whose
      diagnostic procedures included pleural biopsy using video-assisted thoracoscopic
      surgery carried out between 2008 and 2012 were evaluated retrospectively.
      Patients diagnosed with non-specific pleuritis were included. Fifty-three
      patients with available follow-up data were included in the study. RESULTS: Forty
      men and 13 women (mean age 53.9+/-13.9 years) were included. Median follow-up
      time was 24 months. No diagnosis was given in 27 patients (51%), and a clinical
      diagnosis was given in 26 patients (49%) during the follow-up period. Malignant
      disease (malignant mesothelioma) was diagnosed in 2 (3.7%) patients. Other
      diseases were parapneumonic effusion in 12, congestive heart failure in 8, and
      miscellaneous in 4 patients. Volume of effusion at the time of initial
      examination and re-accumulation of fluid after video-assisted thoracoscopic
      surgery were associated with malignant disease (P=.004 and .0001, respectively).
      CONCLUSION: Although the probability is low, some patients with exudative pleural
      effusion undiagnosed after pleural biopsy via video-assisted thoracoscopic
      surgery may have malignant disease. Patients with an initially large volume of
      effusion that re-accumulates after examination should be closely monitored.

PMID- 26216716
TI  - Blindness and Deafness as Initial Manifestation of Non-small Cell Lung Cancer.

PMID- 26216717
TI  - Animal experimentation in forensic sciences: How far have we come?
AB  - In the third millennium where ethical, ethological and cultural evolution seem to
      be leading more and more towards an inter-species society, the issue of animal
      experimentation is a moral dilemma. Speaking from a self-interested human
      perspective, avoiding all animal testing where human disease and therapy are
      concerned may be very difficult or even impossible; such testing may not be so
      easily justifiable when suffering-or killing-of non human animals is inflicted
      for forensic research. In order to verify how forensic scientists are evolving in
      this ethical issue, we undertook a systematic review of the current literature.
      We investigated the frequency of animal experimentation in forensic studies in
      the past 15 years and trends in publication in the main forensic science
      journals. Types of species, lesions inflicted, manner of sedation or anesthesia
      and euthanasia were examined in a total of 404 articles reviewed, among which 279
      (69.1%) concerned studies involving animals sacrificed exclusively for the sake
      of the experiment. Killing still frequently includes painful methods such as
      blunt trauma, electrocution, mechanical asphyxia, hypothermia, and even
      exsanguination; of all these animals, apparently only 60.8% were anesthetized.
      The most recent call for a severe reduction if not a total halt to the use of
      animals in forensic sciences was made by Bernard Knight in 1992. In fact the
      principle of reduction and replacement, frequently respected in clinical
      research, must be considered the basis for forensic science research needing
      animals. 

PMID- 26216718
TI  - Click modification of diazido acridine intercalators: a versatile route towards
      decorated DNA nanostructures.
AB  - Diazido derivatives of 3,6-diamino acridine (proflavine) intercalate into DNA and
      undergo functionalization through click chemistry to form 1D nanostructures with
      redox active, conductive nanowire, and fluorescent properties. This two-step
      approach, intercalation followed by click modification allows for the controlled
      decoration of DNA nanostructures. 

PMID- 26216719
TI  - Quantitative reflection phase mesoscopy by remote coherence tuning of phase-shift
      interference patterns.
AB  - Conventional low-magnification phase-contrast microscopy is an invaluable, yet a
      qualitative, imaging tool for the interrogation of transparent objects over a
      mesoscopic millimeter-scale field-of-view in physical and biological settings.
      Here, we demonstrate that introducing a compact, unbalanced phase-shifting
      Michelson interferometer into a standard reflected brightfield microscope
      equipped with low-power infinity-corrected objectives and white light
      illumination forms a phase mesoscope that retrieves remotely and quantitatively
      the reflection phase distribution of thin, transparent, and weakly scattering
      samples with high temporal (1.38 nm) and spatial (0.87 nm) axial-displacement
      sensitivity and micrometer lateral resolution (2.3 MUm) across a mesoscopic field
      of-view (2.25 * 1.19 mm(2)). Using the system, we evaluate the etch-depth
      uniformity of a large-area nanometer-thick glass grating and show quantitative
      mesoscopic maps of the optical thickness of human cancer cells without any area
      scanning. Furthermore, we provide proof-of-principle of the utility of the system
      for the quantitative monitoring of fluid dynamics within a wide region.

PMID- 26216720
TI  - Indeterminate Growth: Could It Represent the Ancestral Condition?
AB  - Although we are used to the idea that many organisms stop growing when they reach
      a predictable size, in many taxa, growth occurs throughout the life of an
      organism, a phenomenon referred to as indeterminate growth. Our comparative
      analysis suggests that indeterminate growth may indeed represent the ancestral
      condition, whereas the permanent arrest of growth may be a more derived state.
      Consistent with this idea, in diverse taxa, the basal branches show indeterminate
      growth, whereas more derived branches arrest their growth. Importantly, in some
      closely related taxa, the termination of growth has evolved in mechanistically
      distinct ways. Also, even within a single organism, different organs can differ
      with respect to whether they terminate their growth or not. Finally, the study of
      tooth development indicates that, even at the level of a single tissue, multiple
      determinate patterns of growth can evolve from an ancestral one that is
      indeterminate. 

PMID- 26216721
TI  - Lubricin restoration in a mouse model of congenital deficiency.
AB  - OBJECTIVE: Congenital deficiency of the principal boundary lubricant in cartilage
      (i.e., lubricin, encoded by the gene PRG4) increases joint friction and causes
      progressive joint failure. This study was undertaken to determine whether
      restoring lubricin expression in a mouse model would prevent, delay, or reverse
      the disease process caused by congenital deficiency. METHODS: Using genetically
      engineered lubricin-deficient mice, we restored gene function before conception
      or at ages 3 weeks, 2 months, or 6 months after birth. The effect of restoring
      gene function (i.e., expression of lubricin) on the tibiofemoral patellar joints
      of mice was evaluated histologically and by ex vivo biomechanical testing.
      RESULTS: Restoring gene function in mice prior to conception prevented joint
      disease. In 3-week-old mice, restoring gene function improved, but did not
      normalize, histologic features of the articular cartilage and whole-joint
      friction. In addition, cyclic loading of the joints produced fewer activated
      caspase 3-containing chondrocytes when lubricin expression was restored, as
      compared to that in littermate mice whose gene function was not restored
      (nonrestored controls). Restoration of lubricin expression in 2-month-old or 6
      month-old mice had no beneficial effect on histopathologic cartilage damage,
      extent of whole-joint friction, or activation of caspase 3 when compared to
      nonrestored controls. CONCLUSION: When boundary lubrication is congenitally
      deficient and cartilage becomes damaged, the window of opportunity for restoring
      lubrication and slowing disease progression is limited.

PMID- 26216722
TI  - Mortality on the Waiting List for Lung Transplantation in Patients with
      Idiopathic Pulmonary Fibrosis: A Single-Centre Experience.
AB  - PURPOSE: Lung transplantation (LTX) is nowadays accepted as a treatment option
      for selected patients with end-stage pulmonary disease. Idiopathic pulmonary
      fibrosis (IPF) is characterized by the radiological and histologic appearance of
      usual interstitial pneumonia. It is associated with a poor prognosis, and LTX is
      considered an effective treatment to significantly modify the natural history of
      this disease. The aim of the present study was to analyse mortality during the
      waiting list in IPF patients at a single institution. METHODS: A retrospective
      analysis on IPF patients (n = 90) referred to our Lung Transplant Program in the
      period 2001-2014 was performed focusing on patients' characteristics and
      associated risk factors. RESULTS: Diagnosis of IPF was associated with high
      mortality on the waiting list with respect to other diagnosis (p < 0.05). No
      differences in demographic, clinical, radiological data and time spent on the
      waiting list were observed between IPF patients who underwent to LTX or lost on
      the waiting list. Patients who died showed significant higher levels of pCO2 and
      needed higher flows of O2-therapy on effort (p < 0.05). Pulmonary function tests
      failed to predict mortality and no other medical conditions were associated with
      survival. CONCLUSIONS: Patients newly diagnosed with IPF, especially in small to
      medium lung transplant volume centres and in Countries where a long waiting list
      is expected, should be immediately referred to transplantation, delay results in
      increased mortality. Early identification of IPF patients with a rapid
      progressive phenotype is strongly needed.

PMID- 26216723
TI  - A Novel Method for In Vivo Imaging of Solitary Lung Nodules Using Navigational
      Bronchoscopy and Confocal Laser Microendoscopy.
AB  - Solitary pulmonary nodules (SPN) have become increasingly prevalent and
      diagnostic management remains challenging. We demonstrate a novel technique in
      which probe-based confocal endomicroscopy (pCLE) could be performed to microimage
      SPN in vivo and in real-time. Two confocal wavelengths (488 and 660 nm with
      methylene blue (MB)) were used for elastin network and cellular imaging,
      respectively using pCLE in conjunction with r-EBUS and virtual navigation. In the
      first case, the 1-mm Alveoflex was used to image a metastatic melanoma in a
      subcentimetric nodule in the right middle lobe. In the next case, a malignant 2
      cm nodule in the posterior segment of the upper lobe was imaged using the smaller
      0.6-mm Cholangioflex. Lastly, we present a benign case revealing confocal
      characteristics of a nodular lipid pneumonitis. This reports for the first time
      the feasibility and utility of pCLE in vivo microimaging of SPN using either the
      Alveoflex or Cholangioflex miniprobes in addition to 660 nm/MB imaging.

PMID- 26216724
TI  - Outcomes in pediatric patients with nonconvulsive status epilepticus.
AB  - Recognition of nonconvulsive status epilepticus (NCSE) is gaining increasing
      attention in the assessment and evaluation of critically ill pediatric patients.
      The underlying cause of NCSE is often the most important factor in determining
      outcome. However, there is a growing body of literature suggesting that
      electrical seizure burden in NCSE also contributes to unfavorable outcomes.
      Determination of impact of NCSE on outcome based on current evidence involves
      consideration of heterogeneous study settings, study populations, and process of
      care and outcome measures. In addition, the lack of data on neurocognitive
      function prior to episodes of NCSE as well as limited long-term neurocognitive
      assessment data confines precise conclusions about neurocognitive changes. This
      article is part of a Special Issue entitled "Status Epilepticus". 

PMID- 26216725
TI  - Histogram Analysis of CT Perfusion of Hepatocellular Carcinoma for Predicting
      Response to Transarterial Radioembolization: Value of Tumor Heterogeneity
      Assessment.
AB  - PURPOSE: To evaluate in patients with hepatocellular carcinoma (HCC), whether
      assessment of tumor heterogeneity by histogram analysis of computed tomography
      (CT) perfusion helps predicting response to transarterial radioembolization
      (TARE). MATERIALS AND METHODS: Sixteen patients (15 male; mean age 65 years; age
      range 47-80 years) with HCC underwent CT liver perfusion for treatment planning
      prior to TARE with Yttrium-90 microspheres. Arterial perfusion (AP) derived from
      CT perfusion was measured in the entire tumor volume, and heterogeneity was
      analyzed voxel-wise by histogram analysis. Response to TARE was evaluated on
      follow-up imaging (median follow-up, 129 days) based on modified Response
      Evaluation Criteria in Solid Tumors (mRECIST). Results of histogram analysis and
      mean AP values of the tumor were compared between responders and non-responders.
      Receiver operating characteristics were calculated to determine the parameters'
      ability to discriminate responders from non-responders. RESULTS: According to
      mRECIST, 8 patients (50%) were responders and 8 (50%) non-responders. Comparing
      responders and non-responders, the 50th and 75th percentile of AP derived from
      histogram analysis was significantly different [AP 43.8/54.3 vs. 27.6/34.3 mL
      min(-1) 100 mL(-1)); p < 0.05], while the mean AP of HCCs (43.5 vs. 27.9 mL min(
      1) 100 mL(-1); p > 0.05) was not. Further heterogeneity parameters from histogram
      analysis (skewness, coefficient of variation, and 25th percentile) did not differ
      between responders and non-responders (p > 0.05). If the cut-off for the 75th
      percentile was set to an AP of 37.5 mL min(-1) 100 mL(-1), therapy response could
      be predicted with a sensitivity of 88% (7/8) and specificity of 75% (6/8).
      CONCLUSION: Voxel-wise histogram analysis of pretreatment CT perfusion indicating
      tumor heterogeneity of HCC improves the pretreatment prediction of response to
      TARE.

PMID- 26216726
TI  - Biological and nutritional properties of blackcurrant berries (Ribes nigrum L.)
      under conditions of shading nets.
AB  - BACKGROUND: Changes of environmental factors, created under the influence of
      various shading nets, could significantly affect the biological characteristics
      of plants grown in such conditions as well as biosynthesis of primary metabolites
      and ascorbic acid. Five blackcurrant cultivars - 'Ben Sarek', 'Ben Nevis', 'Ben
      Lomond', 'Ometa' and 'Cacanska Crna' - were cultivated in the shade of two green
      polyethylene nets and exposed to direct sunlight during two experimental seasons.
      RESULTS: In the control treatment, all cultivars contained the highest amounts of
      soluble solid content and number of flower buds per shoot in both years of
      cultivation. The bushes exposed to direct sunlight had the highest sunburn damage
      to the berries and leaves, and loss of yield. The greatest yield loss caused by
      berry damage in the present study during the experimental period was in cultivar
      'Ben Sarek': 9.0% in 2010 and 15.4% in 2011. Growing in the shade of light-green
      net contributed the highest content of ascorbic acid. Control bushes and those
      shaded by light-green net had significantly higher radical scavenging activity,
      with values between 1.15 and 1.22 mg mL(-1). CONCLUSION: Plants shaded by nets in
      both years of cultivation had lower damage to leaves and berries and percentage
      of loss of yield, and usage of the net would be economically advantageous to
      growers. Fruit of blackcurrant cultivars grown in shading conditions still
      represent a good source of valuable nutritive and biologically active compounds.

PMID- 26216727
TI  - The effects of CRF and urocortins on the hippocampal glutamate release.
AB  - Corticotropin-releasing factor (CRF) is a hypothalamic neurohormone and an
      extrahypothalamic neurotransmitter that regulates the hypothalamic-pituitary
      adrenal (HPA) axis. The urocortins (UCN I, UCN II and UCN III) are CRF-related
      peptides, which may also regulate the HPA axis directly or indirectly, by
      modulation of extrahypothalamic neurotransmitters, such as amygdalar GABA and
      hippocampal glutamate. Our previous in vitro superfusion studies have already
      demonstrated that CRF and UCN I stimulate the amygdalar GABA release in rats. The
      aim of the present study was to investigate the effects of CRF, UCN I, UCN II and
      UCN III on the glutamate release elicited electrically from rat hippocampal
      slices in similar in vitro conditions. In order to investigate the participation
      of CRF receptors (CRFR1 and CRFR2) in this process, hippocampal slices were
      pretreated with antalarmin, a selective antagonist of CRFR1 or astressin 2B, a
      selective antagonist of CRFR2. CRF and UCN I at 100 nM decreased significantly
      the hippocampal glutamate release evoked by electrical stimulation. In contrast,
      100 nM of UCN II and UCN III did not affect significantly the hippocampal
      glutamate release enhanced by electrical stimulation. The decreasing effects of
      CRF and UCN I were reversed by antalarmin, but not by astressin 2B, both being
      administered in equimolar doses. Our results demonstrate that CRF and UCN I
      inhibit the glutamate release in the hippocampus via CRFR1 and that CRFR2 does
      not participate to this process. Based on the previous and the present results we
      conclude that CRFR1 agonists can activate the HPA axis not only directly, but
      also indirectly by increasing the amygdalar GABA release and decreasing the
      hippocampal glutamate release. 

PMID- 26216728
TI  - Setting the bar: compliance with ovarian cancer quality indicators at a National
      Cancer Institute-designated Comprehensive Cancer Center.
AB  - OBJECTIVES: Ovarian cancer quality measures are being developed to improve health
      care delivery and outcomes. Our objective is to evaluate compliance with 8
      quality indicators proposed by the Society of Gynecologic Oncology. METHODS: A
      review of 123 ovarian cancer patients who underwent primary surgical
      staging/cytoreduction and chemotherapy from 2010-2012 was undertaken. Medical
      records were reviewed, and descriptive statistics were performed to determine
      compliance. RESULTS: A timely operative report documenting residual disease was
      dictated for 121/123 (98.4%) patients. Complete surgical staging was performed in
      33/55 (60.0%) stage I-IIIB patients, with lymphadenectomy most frequently
      omitted. For optimally debulked stage III patients, 52/56 (92.9%) were offered
      intraperitoneal chemotherapy. Ultimately, 29/56 (51.8%) received this route and
      19/56 (33.9%) within 42 days (range 18-48, median 40 days). Clinical trial
      randomization and co-morbidities accounted for most cases of non-compliance. All
      105 patients for whom chemotherapy was indicated received platin/taxane therapy,
      and 79/105 (75.2%) within 42 days (range 4-82, median 37days). Venous
      thromboembolism prophylaxis was provided mechanically in 122/123 (99.2%) and
      pharmacologically in 99/123 (80.5%) patients within 24h of surgery. Prophylactic
      parenteral antibiotics were administered within 60 min of cytoreduction in
      119/123 (96.7%) and discontinued within 24h after surgery in 120/123 (97.6%)
      cases. CONCLUSIONS: Compliance with strict definitions of ovarian cancer quality
      indicators varies depending on the care delivered and documentation of that care.
      Increased attention to comprehensive surgical staging and timely initiation of
      chemotherapy appears warranted. With the move toward value-based payment models,
      quality indicators will play a significant role in health care delivery.

PMID- 26216730
TI  - Heterogeneous Appearance of Central Nervous System Involvement in Malignant Mixed
      Mullerian Tumors.
AB  - Involvement of the central nervous system (CNS) is rarely described in malignant
      mixed Mullerian tumors (MMMTs). Only four intracranial and two spinal cases have
      been published to date. Here we report two more cases with heterogeneous
      clinical, radiologic and pathologic features and summarize the available
      contemporary literature. One patient presented with aphasia due to an intra-axial
      contrast-enhanced left temporal lesion with marked perifocal edema. After
      surgical resection, histology showed collections of small uniform tumor cells
      embedded in a myxoid matrix and compartmentalized by connective tissue
      septations, consistent with an MMMT. The other patient presented with
      trigeminal/tongue hypesthesia and double vision accompanied by left radiculopathy
      and paresis. Magnetic resonance imaging MRI revealed an extraaxial lesion at the
      petrous tip with mild perifocal edema and multiple small intradural contrast
      enhancing lesions of the conus and cauda medullaris. Histologic examination of
      the intracranial lesion showed a mainly papillary architecture, also consistent
      with MMMTs. The spinal lesions were not excised, and both patients received
      adjuvant radiochemotherapy. The first patient died 3 months and the second
      patient 12 months after surgery. As illustrated by the heterogeneous
      clinicopathologic features of our two cases as well as the reviewed literature,
      CNS metastasis of MMMTs is diagnostically challenging, shows a variable outcome,
      and thus requires individualized treatment. In the present cases and CNS
      metastases reported to date, a higher histologic ratio of sarcomatous to
      epithelial components portends a worse outcome. 

PMID- 26216729
TI  - Ascites predicts treatment benefit of bevacizumab in front-line therapy of
      advanced epithelial ovarian, fallopian tube and peritoneal cancers: an NRG
      Oncology/GOG study.
AB  - OBJECTIVES: Predictive factors for efficacy of bevacizumab in advanced ovarian
      cancer have remained elusive. We investigated ascites both as a prognostic factor
      and as a predictor of efficacy for bevacizumab. METHODS: Using data from GOG
      0218, patients receiving cytotoxic therapy plus concurrent and maintenance
      bevacizumab were compared to those receiving cytotoxic therapy plus placebo. The
      presence of ascites was determined prospectively. Chi-square and Wilcoxon-Mann
      Whitney tests compared baseline variables between subgroups. Survival was
      estimated by Kaplan-Meier method, and Cox proportional hazard models were used to
      evaluate independent prognostic factors and estimate their covariate-adjusted
      effects on survival. RESULTS: Treatment arms were balanced with respect to
      ascites and other prognostic factors. Overall, 886 (80%) women had ascites, 221
      (20%) did not. Those with ascites were more likely to have: poorer performance
      status (p<0.001); serous histology (p=0.012); higher baseline CA125 (p<0.001);
      and suboptimal cytoreduction (p=0.004). In multivariate survival analysis,
      ascites was prognostic of poor OS (Adjusted HR 1.22, 95% CI 1.00-1.48, p=0.045),
      but not PFS. In predictive analysis, patients without ascites treated with
      bevacizumab had no significant improvement in either PFS (AHR 0.81, 95% CI 0.59
      1.10, p=0.18) or OS (AHR 0.94, 95% CI 0.65-1.36, p=0.76). Patients with ascites
      treated with bevacizumab had significantly improved PFS (AHR 0.71, 95% CI 0.62
      0.81, p<0.001) and OS (AHR 0.82, 95% CI 0.70-0.96, p=0.014). CONCLUSIONS: Ascites
      in women with advanced ovarian cancer is prognostic of poor overall survival.
      Ascites may predict the population of women more likely to derive long-term
      benefit from bevacizumab.

PMID- 26216731
TI  - Two Cases of Trigeminal Neuralgia Caused by the Trigeminocerebellar Artery.
AB  - The trigeminocerebellar artery (TCA) is a unique branch of the basilar artery. We
      treated two cases of trigeminal neuralgia caused by the TCA. A 72-year-old woman
      had severe typical trigeminal neuralgia for ~ 3 years. Thin-slice T2-weighted
      magnetic resonance imaging revealed an offending TCA. During microvascular
      decompression (MVD), we found that the TCA was compressing the medial aspect of
      the trigeminal nerve. We therefore transposed the TCA loop medially and
      anteriorly away from the nerve and inserted shredded Teflon between the TCA and
      the trigeminal nerve. Postoperatively, this patient's trigeminal neuralgia
      resolved, and she remained pain free at her 24-month follow-up. An 80-year-old
      man had trigeminal neuralgia. Magnetic resonance cisternography revealed that the
      course of the offending artery was the same as that of the TCA, originating from
      the superior cerebellar artery. During the MVD, we performed the same procedure
      as in case 1. Postoperatively, this patient's trigeminal neuralgia resolved, and
      he remained pain free at his 24-month follow-up. Because the TCA has a unique
      anatomical course, its decompression may sometimes be difficult. 

PMID- 26216732
TI  - Subcutaneous Peripheral Nerve Field Stimulation for the Treatment of Chronic Back
      Pain: Patient Selection and Technical Aspects.
AB  - A wide variety of therapeutic options are available for the treatment of chronic
      back pain, a very common condition in Western countries with high related social
      and economic costs. Nevertheless, it is not always possible to achieve adequate
      long-term pain relief in spite of intensive analgesic therapies. Subcutaneous
      peripheral nerve field stimulation (sPNFS) is a newly approved neuromodulative
      treatment for back pain. In previously reported case series, it has provided
      encouraging results on long-term pain relief, improvement in quality of life, and
      a reduced need for analgesic drugs. Although the surgical technique is simple,
      there is neither consensus for patient management nor a standardized procedure
      for the implantation procedure. After consideration of our personal experience
      and the published literature, a basic recommendation has now been developed. This
      represents the first step toward planning prospective studies and standardization
      of this treatment and will permit comparison of this technique and the results
      with sPNFS. 

PMID- 26216733
TI  - Initial Clinical Status and Spot Sign Are Associated with Intraoperative Aneurysm
      Rupture in Patients Undergoing Surgical Clipping for Aneurysmal Subarachnoid
      Hemorrhage.
AB  - OBJECTIVE: To assess clinical and radiographic risk factors for intraoperative
      aneurysm rupture (ioAR) during surgical clipping after aneurysmal subarachnoid
      hemorrhage (aSAH) and to analyze its influence on patient outcome. METHODS:
      Patient selection was based on a retrospective analysis of our prospective
      subarachnoid hemorrhage patient database including consecutive patients between
      January 2008 and August 2012 with aSAH undergoing microsurgical clipping.
      Demographic data, cardiovascular risk factors, preoperative radiologic aneurysm
      characteristics, as well as timing of surgery and preoperative severity grades
      (Hunt and Hess [HH], Fisher, World Federation of Neurological Societies [WFNS]),
      were collected from hospital charts and surgery videos and compared between
      patients with and without ioAR. RESULTS: Of 100 patients (38 men, 62 women) with
      a median age of 57.4 years (range: 23-85 years), ioAR occurred in 34 cases (34%).
      Univariate analyses showed that severity grades were significantly higher in the
      ioAR group (Fisher p = 0.012; HH p = 0.002; WFNS p = 0.023). IoAR was
      significantly associated with intracerebral hemorrhage (ICH) (23% versus 47%; p =
      0.013) and the spot sign as an indicator of active bleeding within the ICH (0% vs
      44%; p = 0.007). Multivariate analysis showed that HH was the only significant
      predictor of ioAR (p = 0.03; odds ratio: 2.3; 95% confidence interval, 1.1-5.0).
      With a mean follow-up of 17.6 months ( +/- 16.6), Glasgow Outcome Scale score,
      mortality rate (12% versus 15%; p = 0.82), delayed cerebral ischemia (36% versus
      38%; p = 0.51), and shunt dependency (32% versus 44%; p = 0.23) were comparable
      between the non-ioAR and ioAR group. CONCLUSIONS: Initial clinical status and
      spot sign were associated with ioAR during microsurgical clipping of ruptured
      aneurysms. However, there was no difference regarding clinical outcome and
      complications of the two groups.

PMID- 26216734
TI  - Clinical, Radiologic, and Legal Significance of "Extensor Response" in
      Posttraumatic Coma.
AB  - OBJECTIVE: The timely detection of neurologic deterioration can be critical for
      the survival of a neurosurgical patient following head injury. Because little
      reliable evidence is available on the prognostic value of the clinical sign
      "extensor response" in comatose posttraumatic patients, we investigated the
      correlation of this clinical sign with outcome and with early radiologic findings
      from magnetic resonance imaging (MRI). METHODS: This retrospective analysis of
      prospectively obtained data included 157 patients who had remained in a coma for
      a minimum of 24 hours after traumatic brain injury. All patients received a 1.5-T
      MRI within 10 days (median: 2 days) of the injury. The correlations between
      clinical findings 12 and 24 hours after the injury-in particular, extensor
      response and pupillary function, MRI findings, and outcome after 1 year-were
      investigated. Statistical analysis included contingency tables, Fisher exact
      test, odds ratios (ORs) with confidence intervals (CIs), and weighted kappa
      values. RESULTS: There were 48 patients with extensor response within the first
      24 hours after the injury. Patients with extensor response (World Federation of
      Neurosurgical Societies coma grade III) statistically were significantly more
      likely to harbor MRI lesions in the brainstem when compared with patients in a
      coma who had no further deficiencies (coma grade I; p = 0.0004 by Fisher exact
      test, OR 10.8 with 95% CI, 2.7-42.5) and patients with unilateral loss of pupil
      function (coma grade II; p = 0.0187, OR 2.8 with 95% CI, 1.2-6.5). The
      correlation of brainstem lesions as found by MRI and outcome according to the
      Glasgow Outcome Scale after 1 year was also highly significant (p <= 0.016).
      CONCLUSION: The correlation of extensor response and loss of pupil function with
      an unfavorable outcome and with brainstem lesions revealed by MRI is highly
      significant. Their sudden onset may be associated with the sudden onset of
      brainstem dysfunction and should therefore be regarded as one of the most
      fundamental warning signs in the clinical monitoring of comatose patients.

PMID- 26216735
TI  - Morphological Parameters of Digital Subtraction Angiography 2D Image in Rupture
      Risk Profile of Small Intracranial Aneurysms: A Pilot Study.
AB  - OBJECTIVE: To analyze the morphological parameters of small intracranial
      aneurysms using two-dimensional digital subtraction angiography (DSA) and to
      identify their relationship with rupture risk. METHODS: Clinical and radiologic
      data from patients with DSA-confirmed small intracranial aneurysms and who
      received intravascular treatment were retrospectively analyzed. Morphological
      parameters such as maximum height, transverse diameter, aneurysm neck width, and
      aspect ratio (AR) were compared between patients with ruptured and unruptured
      aneurysms. Logistic regression analysis was performed to identify the predictors
      of rupture risk. RESULTS: There were no significant differences between the
      unruptured (n = 40) and ruptured groups (n = 34) with respect to maximum height
      (p = 0.087) and transverse diameter (p = 0.736). However, aneurysm neck width (p
      = 0.006) and AR (p < 0.001) were found to be significantly different between the
      groups. AR value was analyzed through the receiver operating characteristic
      curve, and the best AR threshold was determined to be 1.49. A stepwise
      multivariate analysis showed that AR was the only independent factor for rupture
      risk. CONCLUSION: Two-dimensional DSA could be used to determine AR, which was an
      independent predictor of rupture risk of small aneurysms. Further studies with
      large sample sizes are needed to validate these results.

PMID- 26216737
TI  - Clinical Features and Complications in Idiopathic Subarachnoid Hemorrhage: Case
      Studies.
AB  - BACKGROUND: Negative angiography subarachnoid hemorrhage, also known as
      idiopathic subarachnoid hemorrhage (iSAH), is a challenging pathologic condition
      whose evolution and final outcome is difficult to predict with certainty. This
      article describes the clinical features, the type of complications and rates, as
      well as the final outcome of patients with iSAH. METHODS: A prospective
      evaluation of patients with SAH was performed. Patients with a diagnosis of iSAH
      were included. Demographic data, clinical features, complication rates, and
      functional outcomes were all collected. iSAH cases were subsequently compared
      with patients with aneurysmal SAH (aSAH) taken from the same period. RESULTS:
      Forty-nine patients fulfilled the criteria for iSAH. Patients with aSAH presented
      with a worse clinical condition and had a larger amount of blood in the initial
      computed tomography (CT) scan than iSAH patients. There were no differences in
      the incidence of acute hydrocephalus, and there was a positive correlation with
      the Fisher score and the initial clinical status in both groups. Vasospasm was
      more frequent among patients with aSAH, but the relationship between the
      incidence of vasospasm and the amount of blood in the initial CT scan was not
      linear. Good functional outcome was present in > 90% of iSAH patients.
      CONCLUSIONS: Although iSAH generally has a good prognosis, it may be accompanied
      with serious complications. The incidence of acute hydrocephalus in iSAH is
      similar to that in aSAH. There is a lower incidence of vasospasm in iSAH than
      aSAH. A different relationship seems to exist between these complications and the
      amount of blood in the CT scan.

PMID- 26216736
TI  - The Value of Pre- and Intraoperative Adjuncts on the Extent of Resection of
      Hemispheric Low-Grade Gliomas: A Retrospective Analysis.
AB  - BACKGROUND: To achieve maximal resection with minimal risk of postoperative
      neurologic morbidity, different neurosurgical adjuncts are being used during low
      grade glioma (LGG) surgery. OBJECTIVES: To investigate the effect of pre- and
      intraoperative adjuncts on the extent of resection (EOR) of hemispheric LGGs.
      METHODS: Medical records were reviewed to identify patients of any sex, >= 18
      years of age, who underwent LGG surgery at X Hospital between January 2005 and
      July 2013. Patients were divided into eight subgroups based on the use of various
      combinations of a neuronavigation system alone (NN), functional MRI-diffusion
      tensor imaging (fMRI-DTI) guided neuronavigation (FD), intraoperative MRI (MR),
      and direct electrical stimulation (DES). Initial and residual tumors were
      measured, and mean EOR was compared between groups. RESULTS: Of all 128 patients,
      gross total resection was achieved in 23.4%. Overall mean EOR was 81.3% +/-
      20.5%. Using DES in combination with fMRI-DTI (mean EOR: 86.7% +/- 12.4%) on
      eloquent tumors improved mean EOR significantly after adjustment for potential
      confounders when compared with NN alone (mean EOR: 76.4% +/- 25.5%; p = 0.001).
      CONCLUSIONS: Using DES in combination with fMRI and DTI significantly improves
      EOR when LGGs are located in eloquent areas compared with craniotomies in which
      only NN was used.

PMID- 26216738
TI  - Fully Endoscopic Resection of Cerebellopontine Angle Meningiomas.
AB  - OBJECTIVE: To describe our operative technique and results from patients who
      underwent fully endoscopic resection of cerebellopontine angle (CPA) meningiomas.
      DESIGN: Prospective observational study. SETTING: A single academic institution
      that includes both neurosurgery and neuro-otology. PARTICIPANTS: Eleven
      consecutive patients who underwent fully endoscopic resection of a CPA
      meningioma. MAIN OUTCOME MEASURES: Hearing preservation, based on the American
      Association of Otolaryngology-Head and Neck Surgeons score as well as facial
      nerve preservation base on the House-Brackmann (HB) score. In addition, the
      extent of resection and complication rates was studied. RESULTS: All 11 patients
      underwent successful gross total resection, Simpson grade 2, of their meningioma,
      seen both intraoperatively and on postoperative imaging. Overall, 100% of
      patients maintained normal facial nerve function (HB 1/6). Audiometric testing
      revealed that 10 of 11 patients maintained either stable or improved hearing
      postoperatively based on Committee on Hearing and Equilibrium Guidelines for the
      Evaluation of Hearing Preservation in Acoustic Neuroma grade with the remaining
      patient retaining serviceable hearing. Tumor size ranged from 0.5 to 2.5 cm
      (mean: 1.54 cm). Mean operative time was 166 minutes (range: 122-207 minutes);
      estimated blood loss averaged 54.5 mL. Hospital length of stay ranged from 2 to 6
      days (mean: 3.1 days), and a superficial wound infection was the only
      complication seen in one patient. CONCLUSION: Fully endoscopic techniques can be
      used in CPA meningioma resection with excellent clinical results as an
      alternative to the traditional open microscopic approach.

PMID- 26216739
TI  - Supraorbital Keyhole Approach to the Skull Base: Evaluation of Complications
      Related to CSF Fistulas and Opened Frontal Sinus.
AB  - AIM: Cerebrospinal fluid (CSF) rhinorrhea due to a breach in the frontal sinus
      (FS) presents one of the main postoperative complications of the supraorbital
      keyhole approach. The goal of this study was to further analyze the actual
      surgical morbidity and potential risk for patients due to an opened FS after a
      surgery via a supraorbital craniotomy and compare the results with data published
      in the current literature. METHODS AND PATIENTS: A total of 350 consecutive
      patients who underwent surgeries via the supraorbital keyhole approach for
      various lesions were included in this retrospective study. Information on
      clinical history, neurologic symptoms, surgical approach, and postoperative
      complications was obtained retrospectively by a review of the patients' charts,
      the radiologic reports, and a thorough review of pre- and postoperative cranial
      computed tomography (CCT) imaging. RESULTS: The frequency of CSF rhinorrhea after
      this type of craniotomy in the literature is reported to range between 0% and
      9.1%. In this study, analysis of postoperative CCT scans revealed that 88
      patients (25.1%) showed a radiographic breach of the FS. Only 8 of these patients
      (2.3%) developed a CSF leak with rhinorrhea postoperatively. In all cases
      conservative treatment with lumbar drainage failed, and therefore a surgical
      revision for permanent closure was required. Only one patient (0.3%) with a CSF
      leak also developed meningitis. CONCLUSION: Inadvertent opening of the FS during
      the supraorbital craniotomy is a common surgery-related morbidity; however, the
      risk for the patient to develop a potentially dangerous meningitis was found to
      be minimal.

PMID- 26216740
TI  - Vascularized Hypothenar Fat Pad Flap in Revision Surgery for Carpal Tunnel
      Syndrome.
AB  - OBJECTIVE: To evaluate the results of the hypothenar fat pad flap in revision
      surgery for carpal tunnel syndrome (CTS). PATIENTS AND METHODS: We
      retrospectively analyzed 18 consecutive patients (14 women, 4 men) who had
      recurrent CTS. The average age was 61 years. All patients had undergone the index
      carpal tunnel release 5 to 22 months ago. From November 2009 to November 2013,
      they were treated by decompression of the median nerve and a vascularized
      hypothenar fat pad flap. The intraoperative findings were assessed as well as the
      level of pain, recovery of sensory and motor dysfunction, Hoffmann-Tinel sign,
      nerve conduction studies, grip and pinch strength, and Disability of Hand and
      Shoulder Questionnaire (DASH) score. All patients were reevaluated at an average
      of 22 months after revision surgery. RESULTS: After revision surgery, 15 patients
      reported symptomatic improvement. No patient reported worsening of symptoms. A
      median DASH score of 18 was reached. Grip strength recovered to 90% of the
      contralateral side. Overall, 15 patients were satisfied with the result of the
      operation; 3 did not cope with pain and dysfunction. Recurrence was not found in
      any case. CONCLUSION: The hypothenar fat pad flap can be used successfully as an
      adjunct to microsurgical neurolysis for the treatment of recurrent CTS secondary
      to perineural scarring, although a functional deficit remains in some patients.

PMID- 26216741
TI  - Arabidopsis Elongator subunit 2 positively contributes to resistance to the
      necrotrophic fungal pathogens Botrytis cinerea and Alternaria brassicicola.
AB  - The evolutionarily conserved Elongator complex functions in diverse biological
      processes including salicylic acid-mediated immune response. However, how
      Elongator functions in jasmonic acid (JA)/ethylene (ET)-mediated defense is
      unknown. Here, we show that Elongator is required for full induction of the JA/ET
      defense pathway marker gene PLANT DEFENSIN1.2 (PDF1.2) and for resistance to the
      necrotrophic fungal pathogens Botrytis cinerea and Alternaria brassicicola. A
      loss-of-function mutation in the Arabidopsis Elongator subunit 2 (ELP2) alters B.
      cinerea-induced transcriptome reprogramming. Interestingly, in elp2, expression
      of WRKY33, OCTADECANOID-RESPONSIVE ARABIDOPSIS AP2/ERF59 (ORA59), and PDF1.2 is
      inhibited, whereas transcription of MYC2 and its target genes is enhanced.
      However, overexpression of WRKY33 or ORA59 and mutation of MYC2 fail to restore
      PDF1.2 expression and B. cinerea resistance in elp2, suggesting that ELP2 is
      required for induction of not only WRKY33 and ORA59 but also PDF1.2. Moreover,
      elp2 is as susceptible as coronatine-insensitive1 (coi1) and ethylene
      insensitive2 (ein2) to B. cinerea, indicating that ELP2 is an important player in
      B. cinerea resistance. Further analysis of the lesion sizes on the double mutants
      elp2 coi1 and elp2 ein2 and the corresponding single mutants revealed that the
      function of ELP2 overlaps with COI1 and is additive to EIN2 for B. cinerea
      resistance. Finally, basal histone acetylation levels in the coding regions of
      WRKY33, ORA59, and PDF1.2 are reduced in elp2 and a functional ELP2-GFP fusion
      protein binds to the chromatin of these genes, suggesting that constitutive ELP2
      mediated histone acetylation may be required for full activation of the
      WRKY33/ORA59/PDF1.2 transcriptional cascade. 

PMID- 26216742
TI  - Nurses' views of patient participation in nursing care.
AB  - AIMS: To explore nurses' views of patient participation in nursing care on
      medical wards. BACKGROUND: Nurses have frequent contact with patients,
      highlighting their potential role in enabling patient participation. However,
      some nurses' actions and attitudes act as barriers, failing to achieve core
      requirements of patient participation. Discovering nurses' views may assist in
      developing strategies to encourage patient participation in hospitals. DESIGN:
      Interpretive study. METHODS: Twenty nurses were recruited from four medical
      wards, located in two Australian hospitals. In-depth semi-structured interviews
      were conducted between November 2013-March 2014 and analysed using content
      analysis. FINDINGS: Five categories emerged from the nurses' views. The first
      category, acknowledging patients as partners, showed nurses respected patients as
      legitimate participants. In the second category, managing risk, nurses emphasized
      the need to monitor participation to ensure rules and patient safety were
      maintained. Enabling participation was the third category, which demonstrated
      nurses' strategies that enhanced patients' participation. The fourth category was
      hindering participation; encapsulating nurses' difficulty in engaging patients
      with certain characteristics. In the final category, realizing participation,
      nurses believed patients could be involved in physical activities or clinical
      communication. CONCLUSION: Nurses have a crucial role in promoting patient
      participation. Through acknowledging and enabling participation, nurses may
      facilitate patient participation in a range of nursing activities. The nurse's
      role in enacting participation is complex, having to accommodate each patient's
      risks and characteristics, highlighting the need for good assessment skills.
      Education, policy and research strategies are essential to foster nurses' pivotal
      role in patient participation.

PMID- 26216743
TI  - Effect of intraoperative transesophageal Doppler-guided fluid therapy versus
      central venous pressure-guided fluid therapy on renal allograft outcome in
      patients undergoing living donor renal transplant surgery: a comparative study.
AB  - PURPOSE: Transesophageal Doppler (TED)-guided intraoperative fluid therapy has
      shown to noninvasively optimize intravascular volume and reduce postoperative
      morbidity. The aim of this study was to compare the effects of Doppler-guided
      intraoperative fluid administration and central venous pressure (CVP)-guided
      fluid therapy on renal allograft outcome and postoperative complications.
      METHODS: A prospective nonrandomized active controlled study was conducted on end
      stage renal disease patients scheduled for living donor renal transplant surgery.
      110 patients received intraoperative fluid guided by corrected flow time (FTc)
      and variation in stroke volume values obtained by continuous TED monitoring. Data
      of 104 patients in whom intraoperative fluid administration was guided by CVP
      values were retrospectively obtained for a control. RESULTS: The amount of
      intraoperative fluid given in the study group (12.20 +/- 4.24 ml/kg/h) was
      significantly lower than in the controls (22.21 +/- 4.67 ml/kg/h). The amount of
      colloid used was also significantly less and fewer recipients were seen to
      require colloid (69 vs 85%). The mean arterial pressures were comparable
      throughout. CVP reached was 7.18 +/- 3.17 mmHg in the study group. It was
      significantly higher in the controls (13.42 +/- 3.12 mmHg). The postoperative
      graft function and rate of dysfunction were comparable. Side-effects like
      postoperative dyspnoea (4.8 vs 0%) and tissue edema (9.6 vs 2.7%) were higher in
      the controls. CONCLUSIONS: FTc-guided intraoperative fluid therapy achieved the
      same rate of immediate graft function as CVP-guided fluid therapy but used a
      significantly less amount of fluid. The incidence of postoperative complications
      related to fluid overload was also reduced. The use of TED may replace invasive
      central line insertions in the future.

PMID- 26216745
TI  - Diastereoselective synthesis of substituted diaziridines from simple ketones and
      aldehydes.
AB  - Diastereopure substituted diaziridines from simple ketones, aldehydes and amines
      are here reported. These important chemical scaffolds are obtained in the
      presence of a weak inorganic base and hydroxylamine O-sulfonic acid (HOSA). This
      method introduces three stereocenters in one step to provide a wide variety of
      substituted diaziridines with high yields and diastereoselectivities. 

PMID- 26216744
TI  - Usefulness of intraoperative transesophageal echocardiography for evaluation of
      circumflex coronary artery fistula with ruptured aneurysm draining into coronary
      sinus.
AB  - A coronary artery aneurysm (CAA) is defined as dilatation of a coronary artery to
      a diameter >1.5 times that of the adjoining normal coronary artery. Giant CAAs
      with a diameter >= 50 mm are quite rare. Coronary artery fistulas are also
      uncommon, and affected patients require prompt diagnosis and treatment. Coronary
      angiography is the most common method of diagnosing coronary artery fistulas;
      however, transesophageal echocardiography (TEE) can also be a key intraoperative
      tool. In the present report, we describe the case of an 83-year-old man urgently
      admitted to our hospital with pericardial tamponade. Enhanced computed tomography
      and coronary angiography revealed a bulging left main and circumflex artery that
      was connected to a 50-mm diameter CAA. Emergency intraoperative TEE clearly
      showed a CAA with a surrounding hematoma, bulging circumflex artery, and a
      fistulous connection to the coronary sinus; the fistulous vessel contained a
      thrombus. Surgical repair was successful. This case demonstrates that CAA can
      rupture because of spontaneous closure of a thrombus-containing fistula and that
      intraoperative TEE could help to clearly identify the location of the CAA and
      fistulous connection.

PMID- 26216746
TI  - Extended Corannulenes: Aromatic Bowl/Sheet Hybridization.
AB  - Among sheet/sheet polynuclear aromatic hydrocarbon (PAH) hybrids, a buckybowl
      graphene hybrid has been used as a model to explore the effects of physical
      properties of PAHs with distinct planar and bowl regions. Activation of a C(Ar)-F
      bond was used to synthesize this corannulene/graphenic hybrid. Photophysical and
      voltammetric studies together with high-level computations revealed curvature and
      extended pi-effects on the properties of these materials.

PMID- 26216748
TI  - Risk factors for 30-d readmission after colorectal surgery: a systematic review.
AB  - BACKGROUND: Readmission rates after colorectal surgery remain an ongoing clinical
      concern. Recent initiation of penalties for excess readmissions in medical
      patients has encouraged surgeons to reduce readmissions for surgical patients. We
      conducted a systematic review of the published literature for the purpose of
      identifying patient-related risk factors for 30-d readmissions after colorectal
      surgery. METHODS: PubMed and Web of Science were queried for relevant English
      language studies published before January 1, 2015, evaluating 30-d hospital
      readmissions after colorectal surgery in adult patients. Studies were included in
      this review only if they used a multivariable model to assess various patient
      associated predictors and were excluded if the study size was less than 100
      patients. RESULTS: A total of 20 clinical research studies made up of 8 (40%)
      chart reviews and 12 (60%) administrative data met inclusion criteria. Most
      studies took place in the United States, and a variety of procedures (e.g.,
      colectomy, rectal resection, stoma creation) and indications for surgery (e.g.,
      cancer, inflammatory bowel disease, diverticular disease) were evaluated. The
      average ages of included patients was between 37 and 78 y and 36%-97% were men.
      Readmission rates ranged from 9%-25%. Overall, older age, comorbid conditions,
      preoperative immunosuppressive therapy, postoperative complications, and nonhome
      discharge were the most consistent and strongest predictors of readmission.
      CONCLUSIONS: These identifiable risk factors highlight targets for interventions
      in an effort to reduce unplanned readmissions. Determining the most efficacious
      and cost-efficient means to reduce these preventable hospitalizations could save
      millions of valuable health care dollars.

PMID- 26216747
TI  - Inhibition of lipogenesis reduces inflammation and organ injury in sepsis.
AB  - BACKGROUND: Sepsis is a life-threatening acute inflammatory condition associated
      with metabolic complications. Accumulation of free fatty acids (FFAs) induces
      inflammation and causes lipotoxic effects in the liver. Because fatty acid
      metabolism plays a role in the inflammatory response, we hypothesized that the
      administration of C75, a fatty acid synthase inhibitor, could alleviate the
      injury caused by sepsis. METHODS: Male mice were subjected to sepsis by cecal
      ligation and puncture (CLP). At 4 h after CLP, different doses of C75 (1- or 5
      mg/kg body weight) or vehicle (20% dimethyl sulfoxide in saline) were injected
      intraperitoneally. Blood and liver tissues were collected at 24 h after CLP.
      RESULTS: C75 treatment with 1- and 5-mg/kg body weight significantly lowered FFA
      levels in the liver after CLP by 28% and 53%, respectively. Administration of C75
      dose dependently reduced serum indexes of organ injury (aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase) and serum
      levels of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). In
      the liver, C75 treatment reduced inflammation (TNF-alpha and IL-6) and oxidative
      stress (inducible nitric oxide synthase and cyclooxygenase 2) in a dose-dependent
      manner. The 5-mg dose improved the 10-d survival rate to 85% from that of 55% in
      the vehicle. In the presence of C75, TNF-alpha release in RAW 246.7 cells with 4
      h lipopolysaccharide stimulation was also significantly reduced. CONCLUSIONS: C75
      effectively lowered FFA accumulation in the liver, which was associated with
      inhibition of inflammation and organ injury as well as improvement in survival
      rate after CLP. Thus, inhibition of FFA by C75 could ameliorate the hepatic
      dysfunction seen in sepsis.

PMID- 26216749
TI  - Thirty-day readmission after lower extremity bypass in diabetic patients.
AB  - BACKGROUND: Lower extremity bypass (LEB) for peripheral vascular disease is a
      common procedure in diabetics and is associated with readmission. Thus, we
      hypothesized that diabetes might be a predictor of 30-d unplanned readmission
      after LEB. METHODS: Patients undergoing infrainguinal LEB in the 2011-12 American
      College of Surgeons National Surgery Quality Improvement Program database were
      divided into nondiabetics mellitus (NDM), non-insulin-dependent diabetics
      mellitus (NIDDM), and insulin-dependent diabetic mellitus (IDDM). Univariate and
      multivariate analyses were used to evaluate the influence of diabetes on 30-d
      readmission. RESULTS: A total of 9207 patients (5155 [56%] NDM, 1690 (18%) NIDDM,
      and 2362 (26%) IDDM) underwent LEB. Unplanned readmission was observed in 1448
      patients (16%). IDDM had significantly higher crude postoperative complication
      (43% versus 30% NDM, 36% NIDDM; P < 0.001) and unplanned readmission rates (20%
      versus 14% NDM, 16% NIDDM; P < 0.001). Concomitant cardiac disease significantly
      modified the association between diabetes and unplanned readmission. On
      multivariable analysis, IDDM was an independent predictor of unplanned
      readmission in the absence of cardiac disease (odds ratio [OR] = 1.23; 95%
      confidence interval [CI], 1.03-1.47; P = 0.01). However, this association did not
      remain significant in the presence of cardiac disease (OR = 0.70; 95% CI, 0.48
      1.01; P = 0.56). On subgroup analysis of those without cardiac disease, cardiac
      complications were a significant risk factor for readmission in IDDM (OR = 2.00;
      95% CI, 1.12-3.57; P = 0.02) but not NDM (P = 0.31) or NIDDM (P = 0.10).
      CONCLUSIONS: Although post-LEB unplanned readmission was more common among
      diabetics, IDDM was independently associated with unplanned readmission only in
      those without cardiac disease. This was driven, in part, by increased cardiac
      complications. Therefore, a more stringent preoperative cardiac workup in this
      group should be considered before LEB.

PMID- 26216750
TI  - Hyperbaric oxygen preconditioning inhibits skin flap apoptosis in a rat ischemia
      reperfusion model.
AB  - BACKGROUND: Hyperbaric oxygen (HBO) improves skin flap function and inhibits
      partial necrosis induced by ischemia-reperfusion (I/R) injury. Our study aimed to
      evaluate the mechanism underlying HBO regulation of the antiapoptosis factors
      associated with I/R injury of skin flaps. METHODS: The rats were divided into
      sham surgery, I/R, and HBO groups. Rats from the HBO group received HBO
      preconditioning followed by I/R surgery. Blood perfusion of the skin flaps was
      measured with laser Doppler flowmeters. Tissue morphology and apoptosis were
      subsequently assessed based on hematoxylin-eosinhe and terminal deoxynucleotidyl
      transferase dUTP nick-end labeling staining. Protein expression of phosphorylated
      apoptosis signal-regulating kinase 1 (pASK-1), phosphorylated c-Jun N-terminal
      kinase (pJNK), B-cell lymphoma-2 (Bcl-2), and Bcl2-associated X protein (Bax) was
      examined by immunodetection, and Bcl-2 messenger RNA expression was detected by
      quantitative polymerase chain reaction. In addition, caspase-3 activity was also
      measured. RESULTS: The result of microcirculation analysis showed that the
      survival and blood perfusion rates significantly increased in the skin flap after
      HBO exposure. Terminal deoxynucleotidyl transferase dUTP nick-end labeling
      staining revealed that cell apoptosis was significantly attenuated in the HBO
      group. Furthermore, HBO preconditioning increased the expression of Bcl-2 and
      inhibited pASK-1, pJNK, and Bax expression as determined by both
      immunohistochemistry and Western blot. Caspase-3 activity and the Bax/Bcl-2 ratio
      declined in the HBO group. CONCLUSIONS: HBO preconditioning effectively
      ameliorates I/R injury by regulating the apoptosis signal-regulating kinase 1
      and/or c-Jun N-terminal kinase pathway and anti- and proapoptosis factors.

PMID- 26216751
TI  - Centhaquin improves survival in a swine model of hemorrhagic shock.
AB  - BACKGROUND: Hemorrhage is a frequent event in hospital and prehospital settings.
      The aim of the present study was to investigate whether centhaquin improves 24-h
      survival and reduces the total volume of required fluids in an established model
      of swine hemorrhagic shock. MATERIAL AND METHODS: Twenty-five pigs were
      instrumented and subjected to hemorrhagic shock. The animals were randomly
      allocated in two experimental groups, the control (vehicle) (n = 10) and the
      centhaquin groups (0.015 mg/kg, n = 10); all animals received lactated Ringer
      solution in the resuscitation phase until their mean arterial pressure reached
      90% of the baseline. A sham group (n = 5) was added a posteriori to mimic the
      hemodynamic profile of the centhaquin group. RESULTS: A statistically significant
      difference was observed in the time required for the three groups to reach their
      target mean aortic pressure, 36.88 +/- 3.26 min for the control group versus 9.40
      +/- 1.01 min for the sham group and 7.10 +/- 0.97 min for the centhaquin group (P
      < 0.001). The total amount of fluids in the control and the sham groups was
      significantly higher when compared with that of the centhaquin-treated animals (P
      < 0.001). All 10 animals in the centhaquin group survived for 24 h, whereas only
      three animals survived in the control group and one animal in the sham group (P =
      0.002). CONCLUSIONS: Centhaquin 0.015 mg/kg administered in the fluid
      resuscitation phase resulted in lower volume of fluids and better survival
      compared with control and sham-operated animals.

PMID- 26216752
TI  - Story retelling and language ability in school-aged children with cerebral palsy
      and speech impairment.
AB  - BACKGROUND: Research on retelling ability and cognition is limited in children
      with cerebral palsy (CP) and speech impairment. AIMS: To explore the impact of
      expressive and receptive language, narrative discourse dimensions (Narrative
      Assessment Profile measures), auditory and visual memory, theory of mind (ToM)
      and non-verbal cognition on the retelling ability of children with CP and speech
      impairment. METHODS & PROCEDURES: Fifteen speaking children with speech
      impairment (seven girls, eight boys) (mean age = 11 years, SD = 1;4 years), and
      different types of CP and different levels of gross motor and cognitive function
      participated in the present study. Story retelling skills were tested and
      analysed with the Bus Story Test (BST) and the Narrative Assessment Profile
      (NAP). Receptive language ability was tested with the Test for Reception of
      Grammar-2 (TROG-2) and the Peabody Picture Vocabulary Test - IV (PPVT-IV). Non
      verbal cognitive level was tested with the Raven's coloured progressive matrices
      (RCPM), memory functions assessed with the Corsi block-tapping task (CB) and the
      Digit Span from the Wechsler Intelligence Scale for Children-III. ToM was
      assessed with the false belief items of the two story tests "Kiki and the Cat"
      and "Birthday Puppy". OUTCOMES & RESULTS: The children had severe problems with
      retelling ability corresponding to an age-equivalent of 5;2-6;9 years. Receptive
      and expressive language, visuo-spatial and auditory memory, non-verbal cognitive
      level and ToM varied widely within and among the children. Both expressive and
      receptive language correlated significantly with narrative ability in terms of
      NAP total scores, so did auditory memory. CONCLUSION & IMPLICATIONS: The results
      suggest that retelling ability in the children with CP in the present study is
      dependent on language comprehension and production, and memory functions.
      Consequently, it is important to examine retelling ability together with language
      and cognitive abilities in these children in order to provide appropriate
      support.

PMID- 26216753
TI  - Age moderates response to acceptance and commitment therapy vs. cognitive
      behavioral therapy for chronic pain.
AB  - OBJECTIVE: The purpose of this study was to examine age differences in response
      to different forms of psychotherapy for chronic pain. METHODS: We performed a
      secondary analysis of 114 adults (ages 18-89 years) with a variety of chronic,
      nonmalignant pain conditions randomly assigned to 8 weeks of group-administered
      acceptance and commitment therapy (ACT) or cognitive behavioral therapy (CBT).
      Treatment response was defined as a drop of at least three points on the Brief
      Pain Inventory-interference subscale. RESULTS: Older adults were more likely to
      respond to ACT, and younger adults to CBT, both immediately following treatment
      and at 6-month follow-up. There were no significant differences in credibility,
      expectations of positive outcome, attrition, or satisfaction, although there was
      a trend for the youngest adults (ages 18-45 years) to complete fewer sessions.
      CONCLUSIONS: These data suggest that ACT may be an effective and acceptable
      treatment for chronic pain in older adults.

PMID- 26216754
TI  - Glucuronoyl esterases are active on the polymeric substrate methyl esterified
      glucuronoxylan.
AB  - Alkali extracted beechwood glucuronoxylan methyl ester prepared by esterification
      of 4-O-methyl-D-glucuronic acid side residues by methanol was found to serve as
      substrate of microbial glucuronoyl esterases from Ruminococcus flavefaciens,
      Schizophyllum commune and Trichoderma reesei. The enzymatic deesterification was
      monitored by (1)H NMR spectroscopy and evaluated on the basis of the decrease of
      the signal of the ester methyl group and increase of the signal of methanol. The
      results show for the first time the action of enzymes on polymeric substrate,
      which imitates more closely the natural substrate in plant cell walls than the
      low molecular mass artificial substrates used up to present.

PMID- 26216755
TI  - Modulation of the transglycosylation activity of plant family GH18 chitinase by
      removing or introducing a tryptophan side chain.
AB  - Transglycosylation (TG) activity of a family GH18 chitinase from the cycad, Cycas
      revoluta, (CrChiA) was modulated by removing or introducing a tryptophan side
      chain. The removal from subsite +3 through mutation of Trp168 to alanine
      suppressed TG activity, while introduction into subsite +1 through mutation of
      Gly77 to tryptophan (CrChiA-G77W) enhanced TG activity. The crystal structures of
      an inactive double mutant of CrChiA (CrChiA-G77W/E119Q) with one or two N
      acetylglucosamine residues occupying subsites +1 or +1/+2, respectively, revealed
      that the Trp77 side chain was oriented toward +1 GlcNAc to be stacked with it
      face-to-face, but rotated away from subsite +1 in the absence of GlcNAc at the
      subsite. Aromatic residues in the aglycon-binding site are key determinants of TG
      activity of GH18 chitinases. 

PMID- 26216756
TI  - The safety of human papilloma virus-blockers and the risk of triggering
      autoimmune diseases.
AB  - INTRODUCTION: With the safety of human papilloma virus vaccine (HPVv) being
      questioned, this article aims to assess the risks and benefits of the
      commercially available HPVv. Within the last decade, two vaccines (Gardasil and
      Cervarix) have been put on the market to prevent infection with the most
      oncogenic HPV subtypes. Both vaccines contain aluminum adjuvants that are meant
      to cause a hyper stimulated immune response to prevent HPV infection. AREAS
      COVERED: The purpose of this paper is to consider the safety of these two
      vaccines based on the data from the U.S. Vaccine Adverse Event Reporting System
      (VAERS) and case reports. EXPERT OPINION: The current HPVv are both effective and
      generally safe. However, it should be noted that autoimmune side effects have
      been reported in several studies. Further research should be done to understand
      the relationship between HPVv and autoimmunity.

PMID- 26216757
TI  - The effect of repetition priming on spatial memory during backtracking in a novel
      environment.
AB  - During wayfinding in a novel environment, we encounter many new places. Some of
      those places are encoded by our spatial memory. But how does the human brain
      "decides" which locations are more important than others, and how do backtracking
      and repetition priming enhances memorization of these scenes? In this work, we
      explore how backtracking improves encoding of encountered locations. We also
      check whether repetition priming helps with further memory enhancement. We
      recruited 20 adults. Each participant was guided through an unfamiliar indoor
      environment. The participants were instructed to remember the path, as they would
      need to backtrack by themselves. Two groups were defined: the first group
      performed a spatial memory test at the goal destination and after backtracking;
      the second group performed the test only after backtracking. The mean spatial
      memory scores of the first group improved significantly after backtracking: from
      49.8 to 60.8%. The score of the second group was 62%. No difference was found in
      performance between the first group and the second group. Backtracking alone
      significantly improves spatial memory of visited places. Surprisingly, repetition
      priming does not further enhance memorization of these places. This result may
      suggest that spatial reasoning causes significant cognitive load that thwarts
      further improvement of spatial memory of locations.

PMID- 26216758
TI  - Sex differences and errors in the use of terrain slope for navigation.
AB  - Unlike most of the spatial cues that have received attention, a sloping terrain
      can be perceived by multimodal sensory inputs (vision, balance, and kinesthesia),
      making it potentially very salient for navigation. Furthermore, a homogeneous
      slope can be used like a compass to identify directions (e.g., uphill, downhill,
      and sideways), but not to determine distances. We briefly review recent evidence
      on navigation with slope, emphasizing two main findings. On the one hand, we
      focus on the conspicuous sex difference found in the ability to localize a target
      in a square, tilted enclosure; this has emerged in human adults and children, and
      we suggest that it is related to lower awareness of the slope for females. On the
      other hand, we describe the general pattern of errors that arises when localizing
      the target during the task; these errors indicate the use of a bi-coordinate
      representation of the slope. Limitations and ideas for future studies are
      proposed. 

PMID- 26216759
TI  - Situated navigational working memory: the role of positive mood.
AB  - The perspective of situated cognition assumes that cognition is not separated
      from the context. In the present study, the issue if visuospatial memory and
      navigational working memory are situated was explored by manipulating
      participants' mood (positive, negative and neutral) while performing two
      different tasks. College students were randomly assigned to the group of
      positive, negative or neutral music. Participants filled out the positive and
      negative affect schedule (PANAS) before and after carrying out the Corsi Test and
      the Walking Corsi Test. Both tasks were performed forward and backward. Music was
      played throughout the memory tasks. Firstly, comparing pre-mood induction PANAS
      scores to post-mood induction PANAS scores, results showed that only positive
      affects were manipulated: After mood induction, the Positive Music Group produced
      higher scores, whereas the Negative Music Group produced lower scores than before
      mood induction; the Neutral Music Group produced no effect. Secondly, the
      Positive Music Group produced higher scores than Negative and Neutral Music
      Groups both at the Corsi Test and at the Walking Corsi Test. These results show
      that situational contexts that induce a specific mood can affect visuospatial
      memory and navigational working memory, and open to the idea that positive
      emotions may play a crucial role in enhancing navigational strategies. 

PMID- 26216760
TI  - The architect's perspective on the tour and map perspective.
AB  - Literature in linguistics suggests that when people are asked to provide an oral
      spatial description, they usually provide a body-centered narrative; they adopt a
      Tour Perspective, that is, an imaginary tour of the space rather than a Map
      Perspective, that is, a description focused on spatial relations as seen from
      above (Linde and Labov in Language 51(1):924-939, 1975; Howald in Discursive
      constraints on space in narrative: evidence from guilty plea discourse, eVox 3,
      2009). I conducted a pilot experiment to address the following questions: Does
      the formal knowledge of architects--their familiarity with plan drawings and maps
      -override the tendency to adopt the tour perspective? Does the tour perspective
      depend on the actual experience of space? Twenty-two graduate students in
      architecture were asked to respond to the following questions: (1) "Can you
      describe the layout of your apartment?" (2) "Can you describe the layout of an
      ideal apartment?" In the responses to the first question most participants used
      the tour perspective. In the responses to the second question most participants
      used the map perspective. The results provide evidence that architects' formal
      knowledge does not override the preference of the tour perspective in
      descriptions of experienced space. Moreover, that the tour perspective is
      associated with the actual experience of space.

PMID- 26216761
TI  - Strategies in unbounded number line estimation? Evidence from eye-tracking.
AB  - For bounded number line estimation, recent studies indicated influences of
      proportion-based strategies as documented by eye-tracking data. In the current
      study, we investigated solution strategies in bounded and unbounded number line
      estimation by directly comparing participants' estimation performance as well as
      their corresponding eye-fixation behaviour. For bounded number line estimation,
      increased numbers of fixations at and around reference points (i.e. start, middle
      and endpoint) confirmed the prominent use of proportion-based strategies. In
      contrast, in unbounded number line estimation, the number of fixations on the
      number line decreased continuously with increasing magnitude of the target
      number. Additionally, we observed that in bounded and unbounded number line
      estimation participants' first fixation on the number line was a valid predictor
      of the location of the target number. In sum, these data corroborate the idea
      that unbounded number line estimation is less influenced by proportion-based
      estimation strategies not directly related to numerical estimations. 

PMID- 26216762
TI  - Microbial diagnosis of infection and colonization of cardiac implantable
      electronic devices by use of sonication.
AB  - OBJECTIVES: The clinical utility of sonication as an adjunctive diagnostic tool
      for the microbial diagnosis of cardiac implantable device-associated infections
      (CIDAIs) was investigated. METHODS: The implants of 83 subjects were
      investigated, 15 with a CIDAI and 68 without a clinical infection. Clinical data
      were analyzed prospectively and sonication fluid cultures (83 patients, 100%) and
      traditional cultures (31 patients, 37.4%) were performed RESULTS: Generator
      pocket infection and device-related endocarditis were found in 13 (86.7%) and
      four (26.7%) subjects, respectively. The mean numbers of previous technical
      complications and infections were higher in the infected patients compared to the
      non-infected patients (8 vs. 1, p<0.001; 2 vs. 0, p<0.031, respectively). The
      sensitivity and specificity for detecting CIDAI was 73.3% (11/15) and 48.5%
      (33/68) for sonication fluid culture, and 26.7% (4/15) and 100% (16/16) for
      traditional culture (p<0.001), respectively. A higher number of organisms were
      identified by sonication fluid than by tissue culture (58 vs. 4 specimens;
      p<0.001). The most frequent organisms cultured were Gram-positive cocci (66.1%),
      mainly coagulase-negative staphylococci (35.5%). Thirty-five (51.5%) non-infected
      subjects were considered colonized due to the positive identification of
      organisms exclusively through sonication fluid culture. CONCLUSIONS: Sonication
      fluid culture from the removed cardiac implants has the potential to improve the
      microbiological diagnosis of CIDAIs.

PMID- 26216763
TI  - Melioidosis presenting as a mycotic aneurysm in a Korean patient, diagnosed by
      16S rRNA sequencing and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry.
AB  - A case of melioidosis with a mycotic aneurysm is reported. The blood and tissue
      isolates were identified as three different species of Burkholderia using the
      automated identification systems, VITEK 2 and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The
      isolate was confirmed as Burkholderia pseudomallei by 16S rRNA sequencing. The
      typical features of the Gram staining of colonies and 16S rRNA sequencing can be
      useful to identify B. pseudomallei.

PMID- 26216764
TI  - Burden of chikungunya in Latin American countries: estimates of disability
      adjusted life-years (DALY) lost in the 2014 epidemic.

PMID- 26216766
TI  - Probable transmission chains of Middle East respiratory syndrome coronavirus and
      the multiple generations of secondary infection in South Korea.
AB  - BACKGROUND: In May 2015, South Korea reported its first case of Middle East
      respiratory syndrome coronavirus (MERS-CoV) infection in a 68-year-old man with a
      history of travel in the Middle East. In the presence of secondary infections, an
      understanding of the transmission dynamics of the virus is crucial. The aim of
      this study was to characterize the transmission chains of MERS-CoV infection in
      the current South Korean outbreak. METHODS: Individual-level data from multiple
      sources were collected and used for epidemiological analyses. RESULTS: As of July
      14, 2015, 185 confirmed cases of MERS have been reported in the Korean outbreak.
      Three generations of secondary infection, with over half belonging to the second
      generation, could be delineated. Hospital infection was found to be the most
      important cause of virus transmission, affecting largely non-healthcare workers
      (154/184). Healthcare switching has probably accounted for the emergence of
      multiple generations of secondary infection. Fomite transmission may explain a
      significant proportion of the infections occurring in the absence of direct
      contact with infected cases. CONCLUSIONS: Publicly available data from multiple
      sources, including the media, are useful to describe the epidemic history of an
      outbreak. The effective control of MERS-CoV hinges on the upholding of infection
      control standards and an understanding of health-seeking behaviours in the
      community.

PMID- 26216765
TI  - Epidemiological features and trends of Ebola virus disease in West Africa.
AB  - According to a World Health Organization report, the epidemiological features of
      Ebola virus disease (EVD) have changed significantly in West Africa. In this
      study, the new epidemiological features and prevalence trends for EVD in Guinea,
      Liberia, and Sierra Leone are described. It was predicted that the Ebola outbreak
      would end in June 2015. 

PMID- 26216767
TI  - Human rabies in Zhejiang Province, China.
AB  - OBJECTIVES: To explore the epidemiological characteristics of human rabies in
      Zhejiang Province, China. METHODS: Descriptive and statistical analyses were
      performed using data collected through interview with human rabies cases or their
      relatives during 2007 to 2014. A standardized questionnaire was used to collect
      the data. RESULTS: Two hundred and one cases of human rabies were diagnosed in
      Zhejiang Province between 2007 and 2014, with a gradually declining annual
      incidence. Of the rabies cases identified, 61.2% were aged 40-65 years, and the
      male to female ratio was 2.30:1; 63.7% of cases occurred in the summer and
      autumn. The two most reported occupations were farmer (69.2%) and rural laborer
      (15.4%). Wenzhou, Jinhua, and Huzhou were the three cities with the most reported
      cases. The majority of cases (92.8%) were attributed to canines, and 71.0% of
      animal vectors were household animals. Less than half of the cases (41.4%) sought
      wound treatment after exposure. Post-exposure passive immunization was given to
      9.7% and active immunization to 2.3%. Cases with a wound on the head/face only
      had a significantly shorter incubation than those with wounds at other sites
      (p<0.05); cases with a wound on the hand only had a significantly shorter
      incubation than those with a wound on the lower limb below the knee only
      (p<0.001). Non-resident cases were significantly younger (p<0.001) and had a
      shorter disease duration (p=0.015) than locally resident cases. CONCLUSIONS: The
      majority of rabies cases occurred among 40-65-year-old male residents of
      northern, mid-west, and southeast Zhejiang Province. Further health education is
      needed to increase the coverage of post-exposure prophylaxis (PEP) in people
      exposed to possible rabid animals and rabies vaccine use in household animals.

PMID- 26216769
TI  - MR Imaging of Wrist Ligaments.
AB  - This article discusses the normal anatomy and pathologic appearances of the
      intrinsic and extrinsic wrist ligaments using MR Imaging. Technological advances
      in surface coil design and higher magnetic field strengths have improved
      radiologists' ability to consistently visualize these small ligaments in their
      entirety. Wrist ligament anatomy, in the context of proper physiologic function,
      is emphasized, including common normal variants, and their appearances on MR
      imaging. The spectrum of disorders, incorporating overlapping appearances of
      senescent degenerative changes, and destabilizing ligament tears, is outlined.
      The diagnostic performance of MR imaging to date for various ligament
      abnormalities is discussed, along with significant limitations. 

PMID- 26216768
TI  - Approach to MR Imaging of the Elbow and Wrist: Technical Aspects and Innovation.
AB  - Wrist and elbow MR imaging technology is advancing at a dramatic rate. Wrist and
      elbow MR imaging is performed at medium and higher field strengths with more
      specialized surface coils and more variable pulse sequences and postprocessing
      techniques. High field imaging and improved coils lead to an increased signal-to
      noise ratio and increased variety of soft tissue contrast options. Three
      dimensional imaging is improving in terms of usability and artifacts. Some of
      these advances have challenges in wrist and elbow imaging, such as postoperative
      patient imaging, cartilage mapping, and molecular imaging. This review considers
      technical advances in hardware and software and their clinical applications. 

PMID- 26216770
TI  - MR Imaging of the Triangular Fibrocartilage Complex.
AB  - MR imaging has emerged as the mainstay in imaging internal derangement of the
      soft tissues of the musculoskeletal system largely because of superior contrast
      resolution. The complex geometry and diminutive size of the triangular
      fibrocartilage complex (TFCC) and its constituent structures can make optimal
      imaging of the TFCC challenging; therefore, production of clinically useful
      images requires careful optimization of image acquisition parameters. This
      article provides a foundation for advanced TFCC imaging including factors to
      optimize magnetic resonance images, arthrography, detailed anatomy, and
      classification of injury. In addition, clinical presentations and treatments for
      TFCC injury are briefly considered. 

PMID- 26216771
TI  - MR Imaging of Carpal Fractures.
AB  - Timely diagnosis of carpal fractures is important for optimal treatment outcome.
      Magnetic resonance (MR) imaging performed early in the workup can provide an
      accurate and specific diagnosis, as well as uncover developing complications. In
      the absence of carpal fractures, MR imaging can provide alternative diagnoses
      such as other unsuspected fractures involving the distal radius/ulna or hand,
      osseous contusions, and soft-tissue injuries to various ligaments about the
      wrist. Although MR imaging is the imaging modality of choice to assess the
      viability of the proximal fragment in scaphoid nonunion, the optimal imaging
      protocol is not universally agreed upon. 

PMID- 26216772
TI  - Imaging of the Proximal and Distal Radioulnar Joints.
AB  - The proximal and distal radioulnar joints form a unique articular arrangement
      between the radius and ulna, allowing pivot motion of the forearm and positioning
      the hand in space. Typically imaged in conjunction with the elbow, radiographs,
      computed tomography (CT), and MR imaging of the proximal radioulnar joint
      contribute unique diagnostic information. Because dysfunction of the distal
      radioulnar joint is often a result of instability, dynamic CT protocols stressing
      the joint in addition to anatomic imaging with radiographs and MR imaging is
      valuable. Detailed knowledge of the patient's clinical condition and careful
      selection of imaging protocols will maximize the benefits. 

PMID- 26216773
TI  - MR Imaging of the Elbow.
AB  - Almost all movements of the upper extremities during routine daily life and many
      athletic activities require a painless and stable elbow joint. Studying the elbow
      is a diagnostic challenge because of its complex anatomy. MR imaging is an
      extremely important tool in the evaluation of common elbow disorders, the
      spectrum of which ranges from obvious acute lesions to chronic overuse injuries
      whose imaging manifestations can be subtle. 

PMID- 26216774
TI  - Magnetic Resonance Arthrography of the Wrist and Elbow.
AB  - Magnetic resonance (MR) arthrography of the wrist and elbow is useful for
      detecting a variety of intra-articular pathologies. MR dictations should address
      whether intrinsic ligament tears of the wrist are partial-thickness or full
      thickness, and involve the dorsal, membranous, and/or volar components of the
      ligaments. With regard to elbow soft tissue pathology, partial-thickness tears of
      the anterior band of the ulnar collateral ligament in overhead-throwing athletes
      are well evaluated with MR arthrography. MR arthrography also is helpful in
      staging osteochondritis dissecans of the capitellum, caused by repetitive valgus
      impaction injury in adolescent or young adult baseball pitchers. 

PMID- 26216775
TI  - MR Imaging of Soft-Tissue Tumors of the Upper Extremity.
AB  - Certain soft-tissue tumors seem to be specific to the upper extremity; most are
      benign. Knowledge of key magnetic resonance features, with clinical history and
      epidemiologic knowledge, can assist the radiologist in establishing optimal
      diagnosis. Indeterminate lesions require biopsy to exclude malignancy. 

PMID- 26216776
TI  - MR Imaging of the Nerves of the Upper Extremity: Elbow to Wrist.
AB  - The peripheral nervous system is susceptible to a diverse array of pathologic
      insults, broadly categorizable into those entities intrinsic to the nerves
      themselves, either primarily arising within the nerve(s) or direct involvement of
      the nerve(s) secondary to a systemic process, and those processes external to the
      nerve(s) proper but affecting them extrinsically via mass effect, such as
      entrapment neuropathies. The soft tissue contrast inherent to high-quality MR
      imaging allows for outstanding visualization of the peripheral nervous system and
      surrounding structures. This review focuses on the use of MR imaging in the
      diagnosis and management of peripheral nerve disorders of the upper extremity. 

PMID- 26216777
TI  - Magnetic Resonance Angiography of the Upper Extremity.
AB  - The magnetic resonance angiography (MRA) toolbox includes a wide array of
      versatile methods for diagnosis and therapy planning in patients with a variety
      of upper extremity vascular pathologies. MRA can provide excellent image quality
      with high spatial and high temporal resolution without the disadvantages of
      ionizing radiation, iodinated contrast, and operator dependency. Contrast
      enhanced techniques are preferred for their robustness, image quality, and
      shorter scan times. This article provides an overview of the available MRA
      techniques and a description of the clinical entities that are well suited for
      evaluation with contrast-enhanced MRA. 

PMID- 26216778
TI  - Key MR Imaging Features of Common Hand Surgery Conditions.
AB  - The introduction of 3-T MR imaging scanners as well as dedicated wrist coils has
      allowed for scanning of the unique anatomic structures within the hand with
      unprecedented accuracy. In this article, the authors discuss common hand
      conditions, focusing on imaging findings and the utility of MR imaging as it
      pertains to hand surgery. The authors examine its role in the treatment of hand
      deep-space infections, scaphoid fractures, scapholunate ligament injuries, thumb
      ulnar collateral ligament injuries, and ulnar-sided wrist pain. 

PMID- 26216779
TI  - Foreword. MR Imaging of the Elbow and Wrist.

PMID- 26216780
TI  - MR Imaging of the Wrist and Elbow.

PMID- 26216781
TI  - An effective and recyclable adsorbent for the removal of heavy metal ions from
      aqueous system: Magnetic chitosan/cellulose microspheres.
AB  - Development of highly cost-effective, highly operation-convenient and highly
      efficient natural polymer-based adsorbents for their biodegradability and
      biocompatibility, and supply of safe drinking water are the most threatening
      problems in water treatment field. To tackle the challenges, a new kind of
      efficient recyclable magnetic chitosan/cellulose hybrid microspheres was prepared
      by sol-gel method. By embedding magnetic gamma-Fe2O3 nanoparticles in
      chitosan/cellulose matrix drops in NaOH/urea aqueous solution, it combined
      renewability and biocompatibility of chitosan and cellulose as well as magnetic
      properties of gamma-Fe2O3 to create a hybrid system in heavy metal ions removal. 

PMID- 26216782
TI  - Primary hepatic angiosarcoma.

PMID- 26216783
TI  - Upgrading Lignocellulosic Products to Drop-In Biofuels via Dehydrogenative Cross
      Coupling and Hydrodeoxygenation Sequence.
AB  - Life-cycle analysis (LCA) allows the scientific community to identify the sources
      of greenhouse gas (GHG) emissions of novel routes to produce renewable fuels.
      Herein, we integrate LCA into our investigations of a new route to produce drop
      in diesel/jet fuel by combining furfural, obtained from the catalytic dehydration
      of lignocellulosic pentose sugars, with alcohols that can be derived from a
      variety of bio- or petroleum-based feedstocks. As a key innovation, we developed
      recyclable transition-metal-free hydrotalcite catalysts to promote the
      dehydrogenative cross-coupling reaction of furfural and alcohols to give high
      molecular weight adducts via a transfer hydrogenation-aldol condensation pathway.
      Subsequent hydrodeoxygenation of adducts over Pt/NbOPO4 yields alkanes.
      Implemented in a Brazilian sugarcane biorefinery such a process could result in a
      53-79% reduction in life-cycle GHG emissions relative to conventional petroleum
      fuels and provide a sustainable source of low carbon diesel/jet fuel.

PMID- 26216784
TI  - Morphological changes of red blood cells in peripheral blood smear of patients
      with pregnancy-related hypertensive disorders.
AB  - BACKGROUND AND AIMS: Pregnancy-related hypertensive disorders are complications
      in which risk factors are identified such as nulliparity, age, malnutrition,
      obesity and social issues. Those statements are explained by theories of abnormal
      placentation, immunological inadequacy, genetics and oxidative stress, but all
      theories converge in endothelial damage, which is able to mechanically deform and
      hemolyze erythrocytes as they pass through the capillaries. Given the effects of
      endothelial damage, the aim of the study was to determine erythrocyte alterations
      in peripheral blood smear of patients with hypertensive disorders of pregnancy
      that could be used as prognostic condition. METHODS: We performed a prospective,
      descriptive and observational study where all patients with hypertensive
      disorders admitted to the obstetrics and gynecology service of a specialty
      hospital were recruited. Patients who provided signed informed consent underwent
      peripheral blood smear. Results were tabulated in percentage graphics and
      analyzed with Cramer's V based on chi(2). The peripheral blood smear consisted of
      an extended drop of peripheral blood from the patient with subsequent
      hematological staining done with Romanowsky stain. RESULTS: A total of 119
      samples were analyzed; 74% showed abnormal morphology of erythrocytes and the
      most frequent abnormality was the presence of schistocytes in up to 39% of
      samples. Descriptive analysis showed a degree of association to independent
      variables with Cramer's V = 0.41 value (p <0.05). CONCLUSIONS: A high percentage
      of patients with hypertensive disorders of pregnancy show some morphologic
      alterations of erythrocytes in peripheral blood smear.

PMID- 26216785
TI  - Erratum to: Safety and Tolerability of Fingolimod in Latin American Patients with
      Relapsing-Remitting Multiple Sclerosis: The Open-Label FIRST LATAM Study.

PMID- 26216786
TI  - [Can we rule out that fibromyalgia, chronic fatigue syndrome and multiple
      chemical sensitivity are psychosomatic diseases?].

PMID- 26216787
TI  - Postnatal investigation of prenatally induced effects on the vertebral column of
      rats reduces the uncertainty of classification of anomalies.
AB  - Classification of substances as teratogenic is based on the observation of
      external, visceral and skeletal anomalies. Characterization of anomalies as
      variation or malformation is contingent upon their postnatal persistence and
      adversity to health. Lack of information thereof may result in inconsistent or
      incorrect classification. The aim of this work is the examination of vertebral
      skeletal anomalies regarding their postnatal fate on PNDs 7 and 21. The anomalies
      unossified, asymmetric ossification, bipartite ossification, hemicentric, as well
      as misshapen, did not persist up to PND21 and should be classified as a
      variation. The finding, cervical vertebra centrum dumbbell-shaped, should be
      categorized as a malformation due to its continued presence on PND 21. Lumbar
      centrum supernumerary sinister/dexter/sinister+dexter should also be classified
      as a malformation. This study demonstrates that postnatal examination is useful
      and substantially improves the ability to perform a scientifically sound
      classification of an anomaly compared to investigations terminated on GD 21. 

PMID- 26216790
TI  - Prevalence of Walking-Related Motor Fatigue in Persons With Multiple Sclerosis:
      Decline in Walking Distance Induced by the 6-Minute Walk Test.
AB  - OBJECTIVE: To investigate the individual occurrence of walking-related motor
      fatigue in persons with multiple sclerosis (PwMS), according to disability level
      and disease phenotype.Study design This was a cross-sectional, multinational
      study.Participants They were 208 PwMS from 11 centers with Expanded Disability
      Status Scale (EDSS) scores up to 6.5. METHODS: The percentage change in distance
      walked (distance walked index, DWI) was calculated between minute 6 and 1 (DWI(6
      1)) of the 6-Minute Walk Test (6MWT). Its magnitude was used to classify
      participants into 4 subgroups: (1) DWI(6-1)[>=5%], (2) DWI(6-1)[5%; -5%], (3)
      DWI(6-1)[-5%; > -15%], and (4) DWI(6-1)[<=-15%]. The latter group was labeled as
      having walking-related motor fatigue. PwMS were stratified into 5 subgroups based
      on the EDSS (0-2.5, 3-4, 4.5-5.5, 6, 6.5) and 3 subgroups based on MS phenotype
      (relapsing remitting [RR], primary progressive [PP], and secondary progressive
      [SP]). RESULTS: The DWI6-1was >=5% in 16 PwMS (7.7%), between 5% and -5% in 70
      PwMS (33.6%), between -5% and -15% in 58 PwMS (24%), and <=-15% in 64 PwMS
      (30.8%). The prevalence of walking-related motor fatigue (DWI(6-1)[<=-15%]) was
      significantly higher among the progressive phenotype (PP = 50% and SP = 39%; RR =
      15.6%) and PwMS with higher disability level (EDSS 4.5-5.5 = 48.3%, 6 = 46.3% and
      6.5 = 51.5%, compared with EDSS 0-2.5 = 7.8% and 3-4 = 16.7%;P< .05). Stepwise
      multiple regression analysis indicated that EDSS, but not MS phenotype, explained
      a significant part of the variance in DWI(6-1)(R(2)= 0.086;P< .001). CONCLUSION:
      More than one-third of PwMS showed walking-related motor fatigue during the 6MWT,
      with its prevalence greatest in more disabled persons (up to 51%) and in those
      with progressive MS phenotype (up to 50%). Identification of walking-related
      motor fatigue may lead to better-tailored interventions.

PMID- 26216791
TI  - [Who can really benefit from nalmefene? Independent evaluations vs experts with
      conflicts of interest].

PMID- 26216789
TI  - Impact of Shoulder Abduction Loading on Brain-Machine Interface in Predicting
      Hand Opening and Closing in Individuals With Chronic Stroke.
AB  - BACKGROUND: Many individuals with moderate and severe stroke are unable to use
      their paretic hand. Currently, the effect of conventional therapy on regaining
      meaningful hand function in this population is limited. Efforts have been made to
      use brain-machine interfaces (BMIs) to control hand function. To date, almost all
      BMI classification algorithms are designed for detecting hand movements with a
      resting arm. However, many functional movements require simultaneous movements of
      the arm and hand. Arm movement will possibly affect the detection of intended
      hand movements, specifically for individuals with chronic stroke who have muscle
      synergies. The most prevalent upper-extremity synergy-flexor synergy-is expressed
      as an abnormal coupling between shoulder abductors and elbow/wrist/finger
      flexors. OBJECTIVE: We hypothesized that because of flexor synergy, shoulder
      abductor activity would affect the detection of the hand-opening (a movement
      inhibited by flexion synergy) but not the hand-closing task (a movement
      facilitated by the flexion synergy). METHODS: We evaluated the accuracy of a BMI
      classification algorithm in detecting hand-opening versus closing after reaching
      a target with 2 different shoulder-abduction loads in 6 individuals with stroke.
      RESULTS: We found a decreased accuracy in detecting hand opening when an
      individual with stroke intends to open the hand while activating shoulder
      abductors. However, such decreased accuracy with increased shoulder loading was
      not shown while detecting a hand-closing task. CONCLUSIONS: This study supports
      the idea that one should consider the effect of shoulder abduction activity when
      designing BMI classification algorithms for the purpose of restoring hand
      function in individuals with moderate to severe stroke.

PMID- 26216788
TI  - Soy but not bisphenol A (BPA) or the phytoestrogen genistin alters developmental
      weight gain and food intake in pregnant rats and their offspring.
AB  - Endocrine disrupting compounds (EDCs) are hypothesized to promote obesity and
      early puberty but their interactive effects with hormonally active diets are
      poorly understood. Here we assessed individual and combinatorial effects of soy
      diet or the isoflavone genistein (GEN; administered as the aglycone genistin GIN)
      with bisphenol A (BPA) on body weight, ingestive behavior and female puberal
      onset in Wistar rats. Soy-fed dams gained less weight during pregnancy and,
      although they consumed more than dams on a soy-free diet during lactation, did
      not become heavier. Their offspring (both sexes), however, became significantly
      heavier (more pronounced in males) pre-weaning. Soy also enhanced food intake and
      accelerated female pubertal onset in the offspring. Notably, pubertal onset was
      also advanced in females placed on soy diet at weaning. Males exposed to BPA plus
      soy diet, but not BPA alone, had lighter testes. BPA had no independent effects. 

PMID- 26216792
TI  - [Transcranial direct current stimulation (tDCS) for depression: Results of nearly
      a decade of clinical research].
AB  - OBJECTIVE: Since 2006 transcranial direct current stimulation (tDCS) has been
      investigated in the treatment of depression. In this review, we discuss the
      implications and clinical perspectives that tDCS may have as a therapeutic tool
      in depression from the results reported in this domain. METHODS: A comprehensive
      literature review has found nearly thirty articles - all in English - on this
      topic, corresponding to clinical studies, placebo-controlled or not, case reports
      and reviews. RESULTS: Several meta-analyses showed that the antidepressant
      effects of active tDCS are significant against placebo, but variable, mainly due
      to the heterogeneity of the patients included in the studies, for example
      regarding the resistance to antidepressant treatment. CONCLUSIONS: Specific
      recommendations for the use of tDCS in treating depression may not yet be
      available, but some elements of good practice can be highlighted. Of particular
      note is that anodal tDCS of the left prefrontal cortex at 2mA for 20 minutes per
      day has a potential therapeutic value without risk of significant side effects:
      tDCS offers safe conditions for clinical use in the treatment of depression.

PMID- 26216793
TI  - DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy.
AB  - Mutations in the DEPDC5 (DEP domain-containing protein 5) gene are a major cause
      of familial focal epilepsy with variable foci (FFEVF) and are predicted to
      account for 12-37% of families with inherited focal epilepsies. To assess the
      clinical impact of DEPDC5 mutations in familial temporal lobe epilepsy, we
      screened a collection of Italian families with either autosomal dominant lateral
      temporal epilepsy (ADLTE) or familial mesial temporal lobe epilepsy (FMTLE). The
      probands of 28 families classified as ADLTE and 17 families as FMTLE were
      screened for DEPDC5 mutations by whole exome or targeted massive parallel
      sequencing. Putative mutations were validated by Sanger sequencing. We identified
      a DEPDC5 nonsense mutation (c.918C>G; p.Tyr306*) in a family with two affected
      members, clinically classified as FMTLE. The proband had temporal lobe seizures
      with prominent psychic symptoms (deja vu, derealization, and forced thoughts);
      her mother had temporal lobe seizures, mainly featuring visceral epigastric auras
      and anxiety. In total, we found a single DEPDC5 mutation in one of (2.2%) 45
      families with genetic temporal lobe epilepsy, a proportion much lower than that
      reported in other inherited focal epilepsies. 

PMID- 26216794
TI  - DTI-based tractography of the arcuate fasciculus in patients with polymicrogyria
      and language disorders.
AB  - OBJECTIVES: To assess the integrity of the arcuate fasciculus (AF) with diffusion
      tensor imaging (DTI) and tractography in patients with congenital polymicrogyria
      (PMG) and language disorders. METHODS: Twelve patients with PMG and 12 matched
      controls were prospectively evaluated with DTI (32 gradient encoding directions,
      b-value=1000 s/mm(2)) at 3.0T. The AF was virtually dissected with a
      deterministic streamline approach. DTI metrics included FA (fractional
      anisotropy), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity
      (RD). A subset of patients (n=4) was evaluated to assess cognitive performance
      and language skills. RESULTS: Qualitative evaluation revealed several
      abnormalities in tracts size and architecture in nearly all PMG patients.
      Remarkably, in 3 patients with bilateral PMG, the AF was not delineated on both
      hemispheres. In comparison to controls, patients exhibited significant decrease
      of FA (p=0.003) in addition to increase of RD (p=0.03) in the right AF, whereas
      there was significant increase of MD in the left AF (p=0.04). All 4 patients with
      language evaluation had suboptimal performance on lexical fluency and prosodic
      linguistic. CONCLUSIONS: DTI and tractography suggest that the AF is severely
      disrupted in patients with PMG, providing an anatomical in vivo substrate for the
      language disorders commonly associated with these cortical malformations.

PMID- 26216796
TI  - Should we be worrying about the status of anxiety research in Australia and New
      Zealand?

PMID- 26216795
TI  - Causes that influence the detachment rate after Descemet membrane endothelial
      keratoplasty.
AB  - PURPOSE: To investigate Descemet graft (DG) detachment rate after Descemet
      membrane endothelial keratoplasty (DMEK) in relation to DG position. METHODS: A
      total of 175 consecutive pseudophakic eyes that underwent DMEK (175 eyes for
      Fuchs endothelial dystrophy) from September 2009 through February 2014 at the
      Tubingen Eye Hospital DG position were studied retrospectively by surgical video
      at the end of an operation. A group of 45 eyes showed a decentration of the DG
      with a stromal gap of >=1.5 mm over at least 3 clock hours between the
      descematorhexis edge and the DG. DG detachment was documented at a mean follow-up
      of 13.9 +/- 3.7 months after surgery. DG detachment was defined as a detachment
      of 20 % or more of the DG surface area. Various donor characteristics and patient
      characteristics were analyzed. RESULTS: The best spectacle-corrected visual
      acuity (BCVA) in the group of eyes with central well-positioned DG differed
      significantly from those of eyes with decentered DG. The preoperative BCVA in the
      central well-positioned DG group was 0.63 +/- 0.40 logMAR, and in the decentered
      DG group 0.91 +/- 0.51 logMAR (P < 0.001). The postoperative BCVA in the group of
      eyes with central well-positioned DG was 0.12 +/- 0.11 logMAR, and in the group
      with decentered DG 0.23 +/- 0.29 logMAR (P < 0.001). Endothelial cell density and
      patient characteristics such as age, gender, and intraocular pressure did not
      differ significantly between the two groups. The group of eyes with central well
      positioned DG showed DG detachment in 12 %; the group with decentered DG findings
      had DG detachment in 87 % (P < 0.001) at the 12 month follow up. CONCLUSION: The
      present findings demonstrate the importance of central well-positioned DG and the
      relation of disease severity. Central well-positioned DG may reduce the incidence
      of DG detachment. Overlapping of the donor DG and the host Descemet membrane
      seems to be responsible for DG detachment. One possible way to enhance graft
      adhesion could be a larger descematorhexis, which avoids an overlapping. The
      second possible way could be not waiting too long for surgery to reduce disease
      severity.

PMID- 26216797
TI  - Anxiety disorders deserve an integrated systems approach - an interview with Prof
      David Castle.

PMID- 26216800
TI  - A survey of psychiatrists and trainees to determine their level of familiarity
      with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis.

PMID- 26216801
TI  - R: a statistical package and metaphorical free lunch.

PMID- 26216802
TI  - Duty of care versus least restrictive care. The High Court weighs in.

PMID- 26216814
TI  - Epidemiology and Diagnosis of Testis Cancer.
AB  - Testis cancer is the most commonly diagnosed cancer in young men. Most cases
      represent sporadic occurrences. Most commonly it presents at an early stage
      (clinical stage I) and is highly curable with radical orchiectomy. Even more
      advanced stages of testicular cancer are curable with a multimodality treatment
      approach. There are no widely accepted screening strategies for germ cell tumors.
      This article discusses the known risk factors and epidemiology of testis cancer,
      the presentation, and work up for new patients, and the prognosis and cure rates
      based on the staging and current treatment modalities for testis cancer patients.

PMID- 26216815
TI  - Intratubular Germ Cell Neoplasia of the Testis, Bilateral Testicular Cancer, and
      Aberrant Histologies.
AB  - Intratubular germ cell neoplasia (ITGCN) is a precursor lesion for testicular
      germ cell tumors, most of which are early stage. ITGCN is also associated with
      testicular cancer or ITGCN in the contralateral testis, leading to a risk of
      bilateral testicular malignancy. Testicular biopsy detects most cases, and
      orchiectomy is the treatment of choice in patients with unilateral ITGCN. Low
      dose radiation therapy is recommended in patients with bilateral ITGCN or ITGCN
      in the solitary testis, but the long-term risks of infertility and hypogonadism
      need to be discussed with the patient. Rare histologies of primary testicular
      cancer are also discussed. 

PMID- 26216816
TI  - Management of Low-Stage Testicular Seminoma.
AB  - Management of testicular seminoma has benefited from numerous advances in
      imaging, radiotherapy, and chemotherapy over the last 50 years leading to nearly
      100% disease-specific survival for low-stage seminoma. This article examines the
      evaluation and management of low-stage testicular seminoma, which includes
      clinical stage I and IIA disease. Excellent outcomes for stage I seminoma are
      achieved with active surveillance, adjuvant radiotherapy, and adjuvant single
      agent carboplatin. Current areas of research focus on optimizing surveillance
      regimens and minimizing the morbidity and long-term complications of adjuvant
      treatment. Radiotherapy continues to be the primary treatment option for patients
      with clinical stage IIa disease.

PMID- 26216817
TI  - Management of Stage I Nonseminomatous Germ Cell Tumors.
AB  - Testis cancer represents the model for a curable malignancy. Although there is
      consensus about the appropriate management of metastatic (clinical stage [CS] IIC
      III) nonseminomatous germ cell tumor (NSGCT) in terms of the chemotherapy
      regimens, number of cycles, and the surgical resection of postchemotherapy
      residual masses, there remains controversy regarding the appropriate management
      of low-stage NSGCT (CSI-IIB). In this article, the benefits and drawbacks of each
      treatment option are reviewed; an evidence-based approach when confronted with
      such a patient and how to best select a treatment avenue based on the patient's
      clinical and pathologic features are also discussed. 

PMID- 26216818
TI  - The Evolution and Technique of Nerve-Sparing Retroperitoneal Lymphadenectomy.
AB  - The evolution of retroperitoneal lymph node dissection technique and associated
      template modifications for nonseminomatous germ cell tumors have resulted in
      significant improvement in the long-term morbidity. Through the preservation of
      sympathetic nerves via exclusion from or prospective identification within the
      boundaries of resection, maintenance and recovery of antegrade ejaculation are
      achieved. Nerve-sparing strategies in early-stage disease are feasible in most
      patients. Postchemotherapy, select patients can be considered for nerve
      preservation. This article describes the anatomic and physiologic basis for,
      indications and technical aspects of, and functional and oncologic outcomes
      reported after nerve-sparing retroperitoneal lymphadenectomy in testicular
      cancer. 

PMID- 26216819
TI  - Minimally Invasive Retroperitoneal Lymphadenectomy: Current Status.
AB  - Although the standard approach of retroperitoneal lymphadnectomy (RLA) is open
      surgery, laparoscopy is an emerging technique in urology and reports of
      laparoscopic RLA are increasing. This article presents the indications,
      technique, and outcome of RLA as primary treatment and post-cisplatin-based
      chemotherapy by means of laparoscopy. In expert hands RLA is minimally invasive
      and reduces morbidity in comparison with open surgery, with the same oncologic
      outcome. However, patient selection is crucial. 

PMID- 26216820
TI  - The Role of Postchemotherapy Surgery in Germ Cell Tumors.
AB  - Retroperitoneal lymph node dissection after chemotherapy has a proved role in the
      staging and treatment of metastatic testicular cancer. Complete removal of all
      postchemotherapy residual masses in nonseminomatous germ cell tumor should be
      performed. Complete removal of positron emission tomography-avid masses greater
      than 3 cm in pure seminoma should be performed. Outcomes depend on patient
      selection and extent of surgery.

PMID- 26216821
TI  - Desperation Postchemotherapy Retroperitoneal Lymph Node Dissection for Metastatic
      Germ Cell Tumors.
AB  - Patients with persistently elevated serum tumor markers should be monitored for
      marker kinetics and evaluated for nonviable cancer causes of marker elevation.
      Desperation postchemotherapy retroperitoneal lymph node dissection is performed
      in select patients following second-line chemotherapy. Adjuvant postoperative
      chemotherapy is not indicated in patients following second-line chemotherapy. 

PMID- 26216822
TI  - Chemotherapy for Good-Risk Nonseminomatous Germ Cell Tumors: Current Concepts and
      Controversies.
AB  - The rate of diagnosis of germ cell tumors has remained fairly constant. By the
      International Germ Cell Cancer Consensus Classification, roughly 60% of all
      metastatic germ cell tumors are classified as good risk. This group of patients
      has an excellent prognosis, with greater than 90% expectation of cure. Treatment
      standards have not changed much in recent years. This article focuses on key
      concepts in the development of the currently accepted first-line regimens and
      addresses some evolving areas of interest, if not controversy. 

PMID- 26216823
TI  - Late Relapse of Testicular Germ Cell Tumors.
AB  - Germ cell tumors of the testis have an overall survival rate greater than 90% as
      a result of a successful multidisciplinary approach to management. Late relapse
      affects a subset of patients however, and tends to be chemorefractory and the
      overall prognosis is poor. Surgery is the mainstay in management of late relapse
      but salvage chemotherapy can be successful. In this review, the clinical
      presentation and detection of late relapse, clinical outcomes, and predictors of
      survival in late relapse and the importance of a multidisciplinary treatment
      approach for successful management of late relapse are discussed. 

PMID- 26216824
TI  - Role of Extraretroperitoneal Surgery in Patients with Metastatic Germ Cell
      Tumors.
AB  - Surgery remains an integral component of treating metastatic testicular germ cell
      tumors outside the retroperitoneum. Defining the role of surgery in
      extraretroperitoneal (ERP) disease can be challenging because metastases can vary
      in terms their volume, pattern, timing, and responsiveness to systemic therapy.
      Some of the philosophies on treating ERP disease have come from robust data on
      outcomes following postchemotherapy retroperitoneal lymph node dissection. The
      remaining knowledge is gained from retrospective series of different ERP sites
      from institutions with expertise in treating testis cancer. This article
      describes how ERP surgery should be integrated into a multidisciplinary treatment
      plan. 

PMID- 26216825
TI  - Reoperative Retroperitoneal Surgery: Etiology and Clinical Outcome.
AB  - Retroperitoneal recurrences following retroperitoneal lymph node dissection
      (RPLND) are rare events and, with few exceptions, should be regarded as either
      surgical or technical failures, or a result of inappropriate modifications to the
      original RPLND template. Although not a substitute for an adequate initial RPLND,
      reoperative retroperitoneal surgery is a viable option for properly selected
      patients. In the hands of experienced surgeons at tertiary care centers,
      reoperative retroperitoneal surgery is associated with long-term survival in a
      significant proportion of patients, with an acceptable degree of morbidity. 

PMID- 26216826
TI  - Long-term Morbidity of Testicular Cancer Treatment.
AB  - Second malignant neoplasms, cardiovascular disease, neurotoxicity and
      ototoxicity, pulmonary complications, hypogonadism, and nephrotoxicity are
      potentially life-threatening long-term complications of testicular cancer and its
      therapy. This article describes the pathogenesis, risks, and management of these
      late effects experienced by long-term testicular cancer survivors, who are
      defined as individuals who are disease free 5 years or more after primary
      treatment. Testicular cancer survivors should follow applicable national
      guidelines for cancer screening and management of cardiovascular disease risk
      factors. In addition, health care providers should capitalize on the time of
      cancer diagnosis as a teachable moment to introduce and promote lifestyle
      changes.

PMID- 26216827
TI  - Infertility with Testicular Cancer.
AB  - Testicular germ cell cancer is one of the most curable cancers. Most patients are
      treated during their reproductive years, making infertility a significant quality
      of life issue after successful treatment. This focused review evaluates the
      factors that contribute to infertility and specific fertility risks with the
      various testicular cancer treatments. Timing of patient discussions and current
      fertility treatments are reviewed. 

PMID- 26216828
TI  - Testicular Cancer.

PMID- 26216829
TI  - Testicular Cancer. Preface.

PMID- 26216830
TI  - Hypertonic saline for bronchiolitis: a case of less is more.

PMID- 26216831
TI  - Arthritis as presenting manifestation of acute lymphoblastic leukaemia in
      children.
AB  - BACKGROUND: At disease onset, children with acute lymphoblastic leukaemia (ALL)
      may present with arthralgia or even signs of arthritis. This might cause
      misdiagnosis and thereby lead to prolonged diagnostic delay. The present study
      aimed to identify children with ALL with joint involvement and to compare their
      characteristics and outcome with children with ALL without joint involvement.
      METHODS: Case records of 286 children diagnosed with ALL between 1992 and 2013
      were reviewed and analysed in this retrospective, descriptive study. RESULTS:
      Fifty-three (18.5%) children with ALL presented with localised joint pain, and
      half of them had objective signs of arthritis. The mean number of joints involved
      was 2.5, most frequently presenting as asymmetric oligoarthritis. The suspected
      misdiagnosis were reactive arthritis (19/53), osteomyelitis (9/53) and juvenile
      idiopathic arthritis (8/53). Children with joint involvement had less objective
      signs of haematological disease. Cytopenia was absent in 24% in children with
      joint involvement (vs 8% without, p=0.001), 50% had only one cell line affected
      (vs 21%, p=0.0005) and 44% had no organomegaly (vs 29%, p=0.05). Median
      diagnostic delay was 4 vs 2 weeks. The 5-year event-free and overall survival was
      superior for children with joint involvement: 94% vs 87% (p=0.049), and 96% vs
      83% (p=0.044). CONCLUSIONS: ALL with joint involvement is a frequent finding
      (18.5%). The clinical signs of leukaemia are less prominent, but non-articular
      pain should alert the clinician of a possible diagnosis of leukaemia. The overall
      and event-free survivals were superior compared with the children without joint
      involvement.

PMID- 26216832
TI  - Question 1: does vitamin D supplementation prevent acute lower respiratory tract
      infections in children?

PMID- 26216833
TI  - Female genital mutilation in children presenting to a London safeguarding clinic:
      a case series.
AB  - OBJECTIVE: To describe the presentation and management of children referred with
      suspected female genital mutilation (FGM) to a UK safeguarding clinic. DESIGN AND
      SETTING: Case series of all children under 18 years of age referred with
      suspected FGM between June 2006 and May 2014. MAIN OUTCOME MEASURES: These
      include indication for referral, demographic data, circumstances of FGM, medical
      symptoms, type of FGM, investigations and short-term outcome. RESULTS: Of the 47
      girls referred, 27 (57%) had confirmed FGM. According to the WHO classification
      of genital findings, FGM type 1 was found in 2 girls, type 2 in 8 girls and type
      4 in 11 girls. No type 3 FGM was seen. The circumstances of FGM were known in 17
      cases, of which 12 (71%) were performed by a health professional or in a medical
      setting (medicalisation). Ten cases were potentially illegal, yet despite police
      involvement there have been no prosecutions. CONCLUSIONS: This study is an
      important snapshot of FGM within the UK paediatric population. The most frequent
      genital finding was type 4 FGM with no tissue damage or minimal scarring. FGM was
      performed at a young age, with 15% reported under the age of 1 year. The study
      also demonstrated significant medicalisation of FGM, which matches recent trends
      in international data. Type 4 FGM performed in infancy is easily missed on
      examination and so vigilance in assessing children with suspected FGM is
      essential.

PMID- 26216834
TI  - Sex differences in 3,4-methylenedioxypyrovalerone (MDPV)-induced taste avoidance
      and place preferences.
AB  - Synthetic cathinones, otherwise known as "bath salts", have gained significant
      attention in the last few years as a result of increased use and abuse. One such
      compound, 3,4-methylenedioxypyrovalerone (MDPV), is pharmacologically and
      behaviorally similar to cocaine and has been shown to possess both aversive and
      rewarding effects. For a host of other drugs, each of these effects (and their
      relative balance) can be influenced by a variety of factors, including sex, which
      in turn impacts drug taking behavior. In this context, the present assessment
      sought to determine whether males and females differed in MDPV-induced CTA and
      CPP. Both male and female Sprague-Dawley rats underwent a combined CTA/CPP
      procedure, in which an injection of one of three doses of MDPV (1.0, 1.8 or
      3.2mg/kg) was paired with both a novel saccharin solution and a novel environment
      and changes in preferences for these stimuli were examined. Taste avoidance was
      evident in both sexes, although this avoidance was weaker in females compared to
      males. MDPV also produced place preferences in all drug-treated animals, but
      these preferences did not vary as a function of sex. The fact that females showed
      a weaker avoidance response compared to males (despite comparable preferences)
      suggests that females may have a heightened susceptibility to use and abuse of
      MDPV, paralleling results seen with cocaine and other stimulants. The present
      findings extend the behavioral characterization of MDPV and the factors that may
      alter its aversive and rewarding effects. 

PMID- 26216835
TI  - Sex differences in adult Wistar rats in the voluntary consumption of ethanol
      after pre-exposure to ethanol-induced flavor avoidance learning.
AB  - Vulnerability to ethanol abuse may be a function of the balance between the
      opposing (aversive and rewarding) motivational effects of the drug. The study of
      these effects is particularly important for understanding alcohol addiction.
      Research in this field seems to point out that ethanol effects are determined by
      a set of internal factors (sex, ethanol intake history, etc.), as well as by
      environmental conditions surrounding the individual (i.e., stress) and, of
      course, the interactions between all these factors. This work explores sex
      differences in sensitivity to aversive effects of ethanol using the procedure of
      flavor avoidance learning (FAL), as well as the effect of this learning
      experience on subsequent voluntary ethanol consumption, in adult rats. The
      results obtained indicated a slight sex based difference in the amount of FAL
      acquired in that females acquisition was weaker (experiment 1), and a differing
      influence of previous experience with the aversive effects of ethanol on the
      voluntary consumption of the drug for each sex (experiment 2). In particular, it
      was observed that female ethanol-naive rats showed a higher intake level and
      preference for ethanol than both ethanol-experienced female rats and ethanol
      naive male rats. In contrast, the ethanol-experienced male rats showed a greater
      consumption of and preference for ethanol than ethanol-naive male rats and
      ethanol-experienced female rats. These data are discussed noting a range of
      possible explicative factors (sex hormones, hedonic processing, etc.), but
      further studies are warranted to elucidate the mechanisms by which ethanol pre
      exposure influences the subsequent intake of ethanol differently by sex. 

PMID- 26216836
TI  - [What are senior house officers allowed to do, and what not?].

PMID- 26216837
TI  - Impact of NaCl reduction in Danish semi-hard Samsoe cheeses on proliferation and
      autolysis of DL-starter cultures.
AB  - Reduction of sodium chloride (NaCl) in cheese manufacturing is a challenge for
      the dairy industry. NaCl has a profound role on microbial development influencing
      cheese sensory and technological properties. The purpose of this work was to
      investigate how proliferation, distribution and autolysis of two commercial DL
      starter cultures (C1 and C2) used in the production of Danish semi-hard Samsoe
      cheeses were affected by reduced NaCl levels. Cheeses containing <0.3%
      (unsalted), 2.3% (reduced-salt) and 3.4% (normal-salted) (w/v) NaCl in moisture
      were produced and analyzed during 12 weeks of ripening. Lactic acid bacteria
      (LAB), distribution of bacteria as single cells or microcolonies, their viability
      in the cheeses and cell autolysis were monitored during ripening, as well as the
      impact of NaCl content and autolysis on the formation of free amino acids (FAA).
      Reduction of NaCl resulted in higher LAB counts at the early stages of ripening,
      with differences between the two DL-starter cultures. The unsalted cheeses
      produced with C1 had retained a significantly higher number of the initial LAB
      counts (cfu/g) after 1 and 2 weeks of ripening (i.e. 58% and 71%), compared to
      the normal-salted cheeses (i.e. 22% and 21%), whereas no significant difference
      was found between the reduced-salt (i.e. 31% and 35%) and normal-salted cheeses.
      At the later stages of ripening (i.e. 7 and 11 weeks) NaCl had no significant
      influence. For cheeses produced with C2, a significant influence of NaCl was only
      found in cheeses ripened for 7 weeks, where the unsalted and reduced-salt cheeses
      had retained a significantly higher number of the initial LAB counts (cfu/g)
      (i.e. 39% and 38%), compared to the normal-salted cheeses (i.e. 21%). In the
      Samsoe cheeses, bacteria were organized as single cells, in groups of 2-3 cells
      or in groups of >=4 cells. During ripening the decrease in the number of viable
      bacteria was mainly due to a reduction in the number of viable bacteria organized
      in groups of >=4 cells. A negative correlation between NaCl content and PepX
      activity was observed. At the end of ripening the total FAA content was lower in
      the unsalted cheeses, compared to the reduced- and normal-salted cheeses. In
      conclusion, NaCl had a significant influence on proliferation of both DL-starter
      cultures. However, the influence of NaCl on culture development was more
      pronounced in cheeses produced with DL-starter culture C1. As both texture and
      taste are parameters known to be affected by the development of the starter
      culture, the design of starter cultures for reduced NaCl cheeses is recommended.

PMID- 26216838
TI  - Incidental Prostate Cancer Diagnosis During Holmium Laser Enucleation: Assessment
      of Predictors, Survival, and Disease Progression.
AB  - OBJECTIVE: To determine the prevalence and predictors of incidental prostate
      cancer (IPCa) after Holmium laser enucleation of the prostate (HoLEP) and to
      assess its functional and oncological outcomes. METHODS: A prospectively
      maintained database was reviewed for cases with IPCa at the time of HoLEP.
      Patients with preoperative PCa were excluded. Patients were divided into two
      groups based on the presence (group I [GI]) or absence of cancer (group II [GII])
      in histopathology. Univariate and multivariate logistic regression analyses were
      performed. RESULTS: Of 1242 patients, 70 (5.64%) were identified to have IPCa.
      Prostate size was comparable between both groups. GI patients had significantly
      higher preoperative prostate-specific antigen (PSA) and total PSA density (tPSAD)
      compared to cancer-free patients. T1a and T1b adenocarcinomas were detected in 54
      (77.1%) and 16 (22.9%) patients, respectively. After a median follow-up of 48 (1
      171) months, both groups were comparable in all functional outcomes but the
      quality of life was significantly better in GII. Patients' age and preoperative
      tPSAD independently predicted IPCa after HoLEP. A tPSAD cutoff value of 0.092 has
      a sensitivity and specificity of 0.83 and 0.67, respectively. Seven patients
      (11.7%) needed adjuvant therapy while other GI patients opted for active
      surveillance. The Kaplan-Meier analysis demonstrated an overall survival of 72.8%
      at 5 years and 63.5% at 10 years for patients with PCa. CONCLUSION: PCa is not
      uncommonly identified after HoLEP, even in those with negative preoperative
      biopsies. In older patients, total PSAD could be a predictor using a cutoff <0.1.
      After HoLEP, active surveillance for low-grade PCa carries good functional and
      oncological outcomes.

PMID- 26216841
TI  - Methane and VFA production in anaerobic digestion of rice straw under dry, semi
      dry and wet conditions during start-up phase.
AB  - This work investigates the start-up phase of anaerobic digestion in wet, semi-dry
      and dry conditions of rice straw analysing the role of volatile fatty acid (VFA)
      production on process kinetics. Methane production yields and biodegradation
      kinetics in reactors operated under wet semi-dry and dry conditions were
      investigated. The experimental results showed a reduction in the specific final
      methane production yield of 57% and 63% in, respectively, semi-dry (TS = 14.8%)
      and dry (TS = 23.4%) conditions compared to wet (TS = 4.8%) conditions. The total
      VFA concentration and speciation are proposed as indicators of process
      development at different total solids content. High VFA concentrations were found
      in dry conditions, with a maximum total VFA concentration of 2110 mg/kg in dry
      conditions, 930 mg/kg in semi-dry conditions and 180 mg/kg in wet conditions. 

PMID- 26216842
TI  - The binding of pentapeptides to biological and synthetic high affinity heparin.
AB  - Pentapeptides have been shown to bind the synthetic heparin fondaparinux
      (Arixtra) as well the biological heparins dalteparin (Fragmin) and salmon
      heparin. In contrast to heparin binding consensus sequences, the pentapeptides
      are acidic or neutral, with no arginine or histidine residue. The peptides showed
      an effect on in vitro heparin anti-factor X activity with a reduction of
      fondaparinux activity by 65-95%. Heparin binding was further studied by using
      peptide solid phase chromatography and NMR analysis. 

PMID- 26216840
TI  - Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer.
AB  - Sporadic colorectal cancer (CRC) is a somatic genetic disease in which
      pathogenesis is influenced by the local colonic environment and the patient's
      genetic background. Consolidating the knowledge of genetic and epigenetic events
      that occur with initiation, progression, and metastasis of sporadic CRC has
      identified some biomarkers that might be utilized to predict behavior and
      prognosis beyond staging, and inform treatment approaches. Modern next-generation
      sequencing of sporadic CRCs has confirmed prior identified genetic alterations
      and has classified new alterations. Each patient's CRC is genetically unique,
      propelled by 2-8 driver gene alterations that have accumulated within the CRC
      since initiation. Commonly observed alterations across sporadic CRCs have allowed
      classification into a (1) hypermutated group that includes defective DNA mismatch
      repair with microsatellite instability and POLE mutations in ~15%, containing
      multiple frameshifted genes and BRAF(V600E); (2) nonhypermutated group with
      multiple somatic copy number alterations and aneuploidy in ~85%, containing
      oncogenic activation of KRAS and PIK3CA and mutation and loss of heterozygosity
      of tumor suppressor genes, such as APC and TP53; (3) CpG island methylator
      phenotype CRCs in ~20% that overlap greatly with microsatellite instability CRCs
      and some nonhypermutated CRCs; and (4) elevated microsatellite alterations at
      selected tetranucleotide repeats in ~60% that associates with metastatic behavior
      in both hypermutated and nonhypermutated groups. Components from these
      classifications are now used as diagnostic, prognostic, and treatment biomarkers.
      Additional common biomarkers may come from genome-wide association studies and
      microRNAs among other sources, as well as from the unique alteration profile of
      an individual CRC to apply a precision medicine approach to care. 

PMID- 26216839
TI  - Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers.
AB  - Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. One of the
      fundamental processes driving the initiation and progression of CRC is the
      accumulation of a variety of genetic and epigenetic changes in colonic epithelial
      cells. Over the past decade, major advances have been made in our understanding
      of cancer epigenetics, particularly regarding aberrant DNA methylation, microRNA
      (miRNA) and noncoding RNA deregulation, and alterations in histone modification
      states. Assessment of the colon cancer "epigenome" has revealed that virtually
      all CRCs have aberrantly methylated genes and altered miRNA expression. The
      average CRC methylome has hundreds to thousands of abnormally methylated genes
      and dozens of altered miRNAs. As with gene mutations in the cancer genome, a
      subset of these epigenetic alterations, called driver events, are presumed to
      have a functional role in CRC. In addition, the advances in our understanding of
      epigenetic alterations in CRC have led to these alterations being developed as
      clinical biomarkers for diagnostic, prognostic, and therapeutic applications.
      Progress in this field suggests that these epigenetic alterations will be
      commonly used in the near future to direct the prevention and treatment of CRC. 

PMID- 26216843
TI  - CovRS-Regulated Transcriptome Analysis of a Hypervirulent M23 Strain of Group A
      Streptococcus pyogenes Provides New Insights into Virulence Determinants.
AB  - The two-component control of virulence (Cov) regulator (R)-sensor (S) (CovRS)
      regulates the virulence of Streptococcus pyogenes (group A Streptococcus [GAS]).
      Inactivation of CovS during infection switches the pathogenicity of GAS to a more
      invasive form by regulating transcription of diverse virulence genes via CovR.
      However, the manner in which CovRS controls virulence through expression of
      extended gene families has not been fully determined. In the current study, the
      CovS-regulated gene expression profiles of a hypervirulent emm23 GAS strain
      (M23ND/CovS negative [M23ND/CovS(-)]) and a noninvasive isogenic strain
      (M23ND/CovS(+)), under different growth conditions, were investigated. RNA
      sequencing identified altered expression of ~ 349 genes (18% of the chromosome).
      The data demonstrated that M23ND/CovS(-) achieved hypervirulence by allowing
      enhanced expression of genes responsible for antiphagocytosis (e.g., hasABC), by
      abrogating expression of toxin genes (e.g., speB), and by compromising gene
      products with dispensable functions (e.g., sfb1). Among these genes, several
      (e.g., parE and parC) were not previously reported to be regulated by CovRS.
      Furthermore, the study revealed that CovS also modulated the expression of a
      broad spectrum of metabolic genes that maximized nutrient utilization and energy
      metabolism during growth and dissemination, where the bacteria encounter large
      variations in available nutrients, thus restructuring metabolism of GAS for
      adaption to diverse growth environments. From constructing a genome-scale
      metabolic model, we identified 16 nonredundant metabolic gene modules that
      constitute unique nutrient sources. These genes were proposed to be essential for
      pathogen growth and are likely associated with GAS virulence. The genome-wide
      prediction of genes associated with virulence identifies new candidate genes that
      potentially contribute to GAS virulence. IMPORTANCE: The CovRS system modulates
      transcription of ~ 18% of the genes in the Streptococcus pyogenes genome.
      Mutations that inactivate CovR or CovS enhance the virulence of this bacterium.
      We determined complete transcriptomes of a naturally CovS-inactivated invasive
      deep tissue isolate of an emm23 strain of S. pyogenes (M23ND) and its
      complemented avirulent variant (CovS(+)). We identified diverse virulence genes
      whose altered expression revealed a genetic switching of a nonvirulent form of
      M23ND to a highly virulent strain. Furthermore, we also systematically uncovered
      for the first time the comparative levels of expression of a broad spectrum of
      metabolic genes, which reflected different metabolic needs of the bacterium as it
      invaded deeper tissue of the human host.

PMID- 26216845
TI  - Acetate Exposure Determines the Diauxic Behavior of Escherichia coli during the
      Glucose-Acetate Transition.
AB  - Growth of Escherichia coli on glucose in batch culture is accompanied by the
      excretion of acetate, which is consumed by the cells when glucose is exhausted.
      This glucose-acetate transition is classically described as a diauxie (two
      successive growth stages). Here, we investigated the physiological and metabolic
      properties of cells after glucose exhaustion through the analysis of growth
      parameters and gene expression. We found that E. coli cells grown on glucose in
      batch culture produce acetate and consume it after glucose exhaustion but do not
      grow on acetate. Acetate is catabolized, but key anabolic genes--such as the
      genes encoding enzymes of the glyoxylate shunt--are not upregulated, hence
      preventing growth. Both the induction of the latter anabolic genes and growth
      were observed only after prolonged exposure to low concentrations of acetate and
      could be accelerated by high acetate concentrations. We postulate that such
      decoupling between acetate catabolism and acetate anabolism might be an advantage
      for the survival of E. coli in the ever-changing environment of the intestine.
      IMPORTANCE: The glucose-acetate transition is a valuable experimental model for
      comprehensive investigations of metabolic adaptation and a current paradigm for
      developing modeling approaches in systems microbiology. Yet, the work reported in
      our paper demonstrates that the metabolic behavior of Escherichia coli during the
      glucose-acetate transition is much more complex than what has been reported so
      far. A decoupling between acetate catabolism and acetate anabolism was observed
      after glucose exhaustion, which has not been reported previously. This phenomenon
      could represent a strategy for optimal utilization of carbon resources during
      colonization and persistence of E. coli in the gut and is also of significant
      interest for biotechnological applications.

PMID- 26216844
TI  - Acetate Dissimilation and Assimilation in Mycobacterium tuberculosis Depend on
      Carbon Availability.
AB  - Mycobacterium tuberculosis persists inside granulomas in the human lung. Analysis
      of the metabolic composition of granulomas from guinea pigs revealed that one of
      the organic acids accumulating in the course of infection is acetate (B. S.
      Somashekar, A. G. Amin, C. D. Rithner, J. Troudt, R. Basaraba, A. Izzo, D. C.
      Crick, and D. Chatterjee, J Proteome Res 10:4186-4195, 2011,
      doi:http://dx.doi.org/10.1021/pr2003352), which might result either from
      metabolism of the pathogen or might be provided by the host itself. Our studies
      characterize a metabolic pathway by which M. tuberculosis generates acetate in
      the cause of fatty acid catabolism. The acetate formation depends on the
      enzymatic activities of Pta and AckA. Using actyl coenzyme A (acetyl-CoA) as a
      substrate, acetyl-phosphate is generated and finally dephosphorylated to acetate,
      which is secreted into the medium. Knockout mutants lacking either the pta or
      ackA gene showed significantly reduced acetate production when grown on fatty
      acids. This effect is even more pronounced when the glyoxylate shunt is blocked,
      resulting in higher acetate levels released to the medium. The secretion of
      acetate was followed by an assimilation of the metabolite when other carbon
      substrates became limiting. Our data indicate that during acetate assimilation,
      the Pta-AckA pathway acts in concert with another enzymatic reaction, namely, the
      acetyl-CoA synthetase (Acs) reaction. Thus, acetate metabolism might possess a
      dual function, mediating an overflow reaction to release excess carbon units and
      resumption of acetate as a carbon substrate. IMPORTANCE: During infection, host
      derived lipid components present the major carbon source at the infection site.
      beta-Oxidation of fatty acids results in the formation of acetyl-CoA. In this
      study, we demonstrate that consumption of fatty acids by Mycobacterium
      tuberculosis activates an overflow mechanism, causing the pathogen to release
      excess carbon intermediates as acetate. The Pta-AckA pathway mediating acetate
      formation proved to be reversible, enabling M. tuberculosis to reutilize the
      previously secreted acetate as a carbon substrate for metabolism.

PMID- 26216846
TI  - Chemotaxis Control of Transient Cell Aggregation.
AB  - Chemotaxis affords motile cells the ability to rapidly respond to environmental
      challenges by navigating cells to niches favoring growth. Such a property results
      from the activities of dedicated signal transduction systems on the motility
      apparatus, such as flagella, type IV pili, and gliding machineries. Once cells
      have reached a niche with favorable conditions, they often stop moving and
      aggregate into complex communities termed biofilms. An intermediate and
      reversible stage that precedes commitment to permanent adhesion often includes
      transient cell-cell contacts between motile cells. Chemotaxis signaling has been
      implicated in modulating the transient aggregation of motile cells. Evidence
      further indicates that chemotaxis-dependent transient cell aggregation events are
      behavioral responses to changes in metabolic cues that temporarily prohibit
      permanent attachment by maintaining motility and chemotaxis. This minireview
      discusses a few examples illustrating the role of chemotaxis signaling in the
      initiation of cell-cell contacts in bacteria moving via flagella, pili, or
      gliding. 

PMID- 26216847
TI  - Bacillus anthracis SlaQ Promotes S-Layer Protein Assembly.
AB  - Bacillus anthracis vegetative forms assemble an S-layer comprised of two S-layer
      proteins, Sap and EA1. A hallmark of S-layer proteins are their C-terminal
      crystallization domains, which assemble into a crystalline lattice once these
      polypeptides are deposited on the bacterial surface via association between their
      N-terminal S-layer homology domains and the secondary cell wall polysaccharide.
      Here we show that slaQ, encoding a small cytoplasmic protein conserved among
      pathogenic bacilli elaborating S-layers, is required for the efficient secretion
      and assembly of Sap and EA1. S-layer protein precursors cosediment with SlaQ, and
      SlaQ appears to facilitate Sap assembly. Purified SlaQ polymerizes and when mixed
      with purified Sap promotes the in vitro formation of tubular S-layer structures.
      A model is discussed whereby SlaQ, in conjunction with S-layer secretion factors
      SecA2 and SlaP, promotes localized secretion and S-layer assembly in B.
      anthracis. IMPORTANCE: S-layer proteins are endowed with the propensity for self
      assembly into crystalline arrays. Factors promoting S-layer protein assembly have
      heretofore not been reported. We identified Bacillus anthracis SlaQ, a small
      cytoplasmic protein that facilitates S-layer protein assembly in vivo and in
      vitro.

PMID- 26216848
TI  - The DNA-Binding Protein from Starved Cells (Dps) Utilizes Dual Functions To
      Defend Cells against Multiple Stresses.
AB  - Bacteria deficient in the DNA-binding protein from starved cells (Dps) are viable
      under controlled conditions but show dramatically increased mortality rates when
      exposed to any of a wide range of stresses, including starvation, oxidative
      stress, metal toxicity, or thermal stress. It remains unclear whether the
      protective action of Dps against specific stresses derives from its DNA-binding
      activity, which may exclude destructive agents from the chromosomal region, or
      its ferroxidase activity, which neutralizes and sequesters potentially damaging
      chemical species. To resolve this question, we have identified the critical
      residues of Escherichia coli Dps that bind to DNA and modulate iron oxidation. We
      uncoupled the biochemical activities of Dps, creating Dps variants and mutant E.
      coli strains that are defective in either DNA-binding or ferroxidase activity.
      Quantification of the contribution of each activity to the protection of DNA
      integrity and cellular viability revealed that both activities of Dps are
      required in order to counteract many differing stresses. These findings
      demonstrate that Dps plays a multipurpose role in stress protection via its dual
      activities, explaining how Dps can be of vital importance to bacterial viability
      over a wide range of stresses. IMPORTANCE: The DNA-binding protein from starved
      cells (Dps) protects bacterial cells against many different types of stressors.
      We find that DNA binding and iron oxidation by Dps are performed completely
      independently of each other. Both biochemical activities are required to protect
      E. coli against stressors, as well as to protect DNA from oxidative damage in
      vitro. These results suggest that many stressors may cause both oxidative stress
      and direct DNA damage.

PMID- 26216849
TI  - Chlamydia trachomatis Type III Secretion Proteins Regulate Transcription.
AB  - The Scc4 protein (CT663) of the pathogenic bacterium Chlamydia has been described
      as a type III secretion (T3S) chaperone as well as an inhibitor of RNA
      polymerase. To examine if these roles are connected, we first investigated
      physical interactions between Chlamydia trachomatis Scc4 and the T3S chaperone
      Scc1 and a T3S substrate, CopN. In a yeast 3-hybrid assay, Scc4, Scc1, and CopN
      were all required to detect an interaction, which suggests that these proteins
      form a trimolecular complex. We also detected interactions between any two of
      these three T3S proteins in a pulldown assay using only recombinant proteins. We
      next determined whether these interactions affected the function of Scc4 as an
      inhibitor of RNA transcription. Using Escherichia coli as a heterologous in vivo
      system, we demonstrated that expression of C. trachomatis Scc4 led to a drastic
      decrease in transcript levels for multiple genes. However, coexpression of Scc4
      with Scc1, CopN, or both alleviated Scc4-mediated inhibition of transcription.
      Scc4 expression also severely impaired E. coli growth, but this growth defect was
      reversed by coexpression of Scc4 with Scc1, CopN, or both, suggesting that the
      inhibitory effect of Scc4 on transcription and growth can be antagonized by
      interactions between Scc4, Scc1, and CopN. These findings suggest that the dual
      functions of Scc4 may serve as a bridge to link T3S and the regulation of gene
      expression in Chlamydia. IMPORTANCE: This study investigates a novel mechanism
      for regulating gene expression in the pathogenic bacterium Chlamydia. The
      Chlamydia type III secretion (T3S) chaperone Scc4 has been shown to inhibit
      transcription by RNA polymerase. This study describes physical interactions
      between Scc4 and the T3S proteins Scc1 and CopN. Furthermore, Chlamydia Scc1 and
      CopN antagonized the inhibitory effects of Scc4 on transcription and growth in a
      heterologous Escherichia coli system. These results provide evidence that
      transcription in Chlamydia can be regulated by the T3S system through
      interactions between T3S proteins.

PMID- 26216851
TI  - Sparsity techniques in medical imaging.

PMID- 26216850
TI  - Cyclic Dinucleotide-Controlled Regulatory Pathways in Streptomyces  Species.
AB  - The cyclic dinucleotides cyclic 3',5'-diguanylate (c-di-GMP) and cyclic 3',5'
      diadenylate (c-di-AMP) have emerged as key components of bacterial signal
      transduction networks. These closely related second messengers follow the
      classical general principles of nucleotide signaling by integrating diverse
      signals into regulatory pathways that control cellular responses to changing
      environments. They impact distinct cellular processes, with c-di-GMP having an
      established role in promoting bacterial adhesion and inhibiting motility and c-di
      AMP being involved in cell wall metabolism, potassium homeostasis, and DNA
      repair. The involvement of c-dinucleotides in the physiology of the filamentous,
      nonmotile streptomycetes remained obscure until recent discoveries showed that c
      di-GMP controls the activity of the developmental master regulator BldD and that
      c-di-AMP determines the level of the resuscitation-promoting factor A(RpfA) cell
      wall-remodelling enzyme. Here, I summarize our current knowledge of c
      dinucleotide signaling in Streptomyces species and highlight the important roles
      of c-di-GMP and c-di-AMP in the biology of these antibiotic-producing,
      multicellular bacteria.

PMID- 26216852
TI  - Hippocampal Insulin Resistance Impairs Spatial Learning and Synaptic Plasticity.
AB  - Insulin receptors (IRs) are expressed in discrete neuronal populations in the
      central nervous system, including the hippocampus. To elucidate the functional
      role of hippocampal IRs independent of metabolic function, we generated a model
      of hippocampal-specific insulin resistance using a lentiviral vector expressing
      an IR antisense sequence (LV-IRAS). LV-IRAS effectively downregulates IR
      expression in the rat hippocampus without affecting body weight, adiposity, or
      peripheral glucose homeostasis. Nevertheless, hippocampal neuroplasticity was
      impaired in LV-IRAS-treated rats. High-frequency stimulation, which evoked robust
      long-term potentiation (LTP) in brain slices from LV control rats, failed to
      evoke LTP in LV-IRAS-treated rats. GluN2B subunit levels, as well as the basal
      level of phosphorylation of GluA1, were reduced in the hippocampus of LV-IRAS
      rats. Moreover, these deficits in synaptic transmission were associated with
      impairments in spatial learning. We suggest that alterations in the expression
      and phosphorylation of glutamate receptor subunits underlie the alterations in
      LTP and that these changes are responsible for the impairment in hippocampal
      dependent learning. Importantly, these learning deficits are strikingly similar
      to the impairments in complex task performance observed in patients with
      diabetes, which strengthens the hypothesis that hippocampal insulin resistance is
      a key mediator of cognitive deficits independent of glycemic control. 

PMID- 26216853
TI  - Acute Versus Progressive Onset of Diabetes in NOD Mice: Potential Implications
      for Therapeutic Interventions in Type 1 Diabetes.
AB  - Most natural history models for type 1 diabetes (T1D) propose that overt
      hyperglycemia results after a progressive loss of insulin-secreting beta-cell
      mass and/or function. To experimentally address this concept, we prospectively
      determined morning blood glucose measurements every other day in multiple cohorts
      (total n = 660) of female NOD/ShiLtJ mice starting at 8 weeks of age until
      diabetes onset or 26 weeks of age. Consistent with this notion, a majority of
      mice that developed diabetes (354 of 489 [72%]) displayed a progressive increase
      in blood glucose with transient excursions >200 mg/dL, followed by acute and
      persistent hyperglycemia at diabetes onset. However, 135 of the 489 (28%)
      diabetic animals demonstrated normal glucose values followed by acute (i.e.,
      sudden) hyperglycemia. Interestingly, diabetes onset occurred earlier in mice
      with acute versus progressive disease onset (15.37 +/- 0.3207 vs. 17.44 +/-
      0.2073 weeks of age, P < 0.0001). Moreover, the pattern of onset (i.e.,
      progressive vs. acute) dramatically influenced the ability to achieve reversal of
      T1D by immunotherapeutic intervention, with increased effectiveness observed in
      situations of a progressive deterioration in euglycemia. These studies highlight
      a novel natural history aspect in this animal model, one that may provide
      important guidance for the selection of subjects participating in human trials
      seeking disease reversal. 

PMID- 26216854
TI  - Elevations in Circulating Methylated and Unmethylated Preproinsulin DNA in New
      Onset Type 1 Diabetes.
AB  - Elevated ratios of circulating unmethylated to methylated preproinsulin (INS) DNA
      have been suggested to reflect beta-cell death in type 1 diabetes (T1D). We
      tested the hypothesis that absolute levels (rather than ratios) of unmethylated
      and methylated INS DNA differ between subjects with new-onset T1D and control
      subjects and assessed longitudinal changes in these parameters. We used droplet
      digital PCR to measure levels of unmethylated and methylated INS DNA in serum
      from subjects at T1D onset and at 8 weeks and 1 year post-onset. Compared with
      control subjects, levels of both unmethylated and methylated INS DNA were
      elevated at T1D onset. At 8 weeks post-onset, methylated INS DNA remained
      elevated, but unmethylated INS DNA fell. At 1 year postonset, both unmethylated
      and methylated INS DNA returned to control levels. Subjects with obesity, type 2
      diabetes, and autoimmune hepatitis exhibited lower levels of unmethylated and
      methylated INS compared with subjects with T1D at onset and no differences
      compared with control subjects. Our study shows that elevations in both
      unmethylated and methylated INS DNA occurs in new-onset T1D and that levels of
      these DNA species change during T1D evolution. Our work emphasizes the need to
      consider absolute levels of differentially methylated DNA species as potential
      biomarkers of disease. 

PMID- 26216855
TI  - Iron and oxidative stress in cardiomyopathy in thalassemia.
AB  - With repeated blood transfusions, patients with thalassemia major rapidly become
      loaded with iron, often surpassing hepatic metal accumulation capacity within
      ferritin shells and infiltrating heart and endocrine organs. That pathological
      scenario contrasts with the physiological one, which is characterized by an
      efficient maintenance of all plasma iron bound to circulating transferrin, due to
      a tight control of iron ingress into plasma by the hormone hepcidin. Within
      cells, most of the acquired iron becomes protein-associated, as once released
      from endocytosed transferrin, it is used within mitochondria for the synthesis of
      protein prosthetic groups or it is incorporated into enzyme active centers or
      alternatively sequestered within ferritin shells. A few cell types also express
      the iron extrusion transporter ferroportin, which is under the negative control
      of circulating hepcidin. However, that system only backs up the major cell
      regulated iron uptake/storage machinery that is poised to maintain a basal level
      of labile cellular iron for metabolic purposes without incurring potentially
      toxic scenarios. In thalassemia and other transfusion iron-loading conditions,
      once transferrin saturation exceeds about 70%, labile forms of iron enter the
      circulation and can gain access to various types of cells via resident
      transporters or channels. Within cells, they can attain levels that exceed their
      ability to chemically cope with labile iron, which has a propensity for
      generating reactive oxygen species (ROS), thereby inducing oxidative damage. This
      scenario occurs in the heart of hypertransfused thalassemia major patients who do
      not receive adequate iron-chelation therapy. Iron that accumulates in
      cardiomyocytes forms agglomerates that are detected by T2* MRI. The labile forms
      of iron infiltrate the mitochondria and damage cells by inducing noxious ROS
      formation, resulting in heart failure. The very rapid relief of cardiac
      dysfunction seen after intensive iron-chelation therapy in some patients with
      thalassemia major is thought to be due to the relief of the cardiac mitochondrial
      dysfunction caused by oxidative stress or to the removal of labile iron
      interference with calcium fluxes through cardiac calcium channels. In fact,
      improvement occurs well before there is any significant improvement in the total
      level of cardiac iron loading. The oral iron chelator deferiprone, because of its
      small size and neutral charge, demonstrably enters cells and chelates labile
      iron, thereby rapidly reducing ROS formation, allowing better mitochondrial
      activity and improved cardiac function. Deferiprone may also rapidly improve
      arrhythmias in patients who do not have excessive cardiac iron. It maintains the
      flux of iron in the direction hemosiderin to ferritin to free iron, and it allows
      clearance of cardiac iron in the presence of other iron chelators or when used
      alone. To date, the most commonly used chelator combination therapy is
      deferoxamine plus deferiprone, whereas other combinations are in the process of
      assessment. In summary, it is imperative that patients with thalassemia major
      have iron chelators continuously present in their circulation to prevent exposure
      of the heart to labile iron, reduce cardiac toxicity, and improve cardiac
      function. 

PMID- 26216856
TI  - A new standard: A review of Handbook of Ion Channels.

PMID- 26216857
TI  - What keeps Kv channels small? The molecular physiology of modesty.

PMID- 26216858
TI  - Location, Location, Location: Juxtaposed calcium-signaling microdomains as a
      novel model of the vascular smooth muscle myogenic response.

PMID- 26216859
TI  - Pore dimensions and the role of occupancy in unitary conductance of Shaker K
      channels.
AB  - K channels mediate the selective passage of K(+) across the plasma membrane by
      means of intimate interactions with ions at the pore selectivity filter located
      near the external face. Despite high conservation of the selectivity filter, the
      K(+) transport properties of different K channels vary widely, with the unitary
      conductance spanning a range of over two orders of magnitude. Mutation of Pro475,
      a residue located at the cytoplasmic entrance of the pore of the small
      intermediate conductance K channel Shaker (Pro475Asp (P475D) or Pro475Gln
      (P475Q)), increases Shaker's reported ~ 20-pS conductance by approximately six-
      and approximately threefold, respectively, without any detectable effect on its
      selectivity. These findings suggest that the structural determinants underlying
      the diversity of K channel conductance are distinct from the selectivity filter,
      making P475D and P475Q excellent probes to identify key determinants of the K
      channel unitary conductance. By measuring diffusion-limited unitary outward
      currents after unilateral addition of 2 M sucrose to the internal solution to
      increase its viscosity, we estimated a pore internal radius of capture of ~ 0.82
      A for all three Shaker variants (wild type, P475D, and P475Q). This estimate is
      consistent with the internal entrance of the Kv1.2/2.1 structure if the effective
      radius of hydrated K(+) is set to ~ 4 A. Unilateral exposure to sucrose allowed
      us to estimate the internal and external access resistances together with that of
      the inner pore. We determined that Shaker resistance resides mainly in the inner
      cavity, whereas only ~ 8% resides in the selectivity filter. To reduce the inner
      resistance, we introduced additional aspartate residues into the internal
      vestibule to favor ion occupancy. No aspartate addition raised the maximum
      unitary conductance, measured at saturating [K(+)], beyond that of P475D,
      suggesting an ~ 200-pS conductance ceiling for Shaker. This value is
      approximately one third of the maximum conductance of the large conductance K
      (BK) channel (the K channel of highest conductance), reducing the energy gap
      between their K(+) transport rates to ~ 1 kT. Thus, although Shaker's pore
      sustains ion translocation as the BK channel's does, higher energetic costs of
      ion stabilization or higher friction with the ion's rigid hydration cage in its
      narrower aqueous cavity may entail higher resistance.

PMID- 26216860
TI  - Sphingomyelinase D inhibits store-operated Ca2+ entry in T lymphocytes by
      suppressing ORAI current.
AB  - Infections caused by certain bacteria including Mycobacterium tuberculosis and
      Corynebacterium pseudotuberculosis provoke inflammatory responses characterized
      by the formation of granulomas with necrotic foci-so-called caseous necrosis. The
      granulomas of infected animals show prominent infiltration by T lymphocytes, and
      T cell depletion increases host mortality. Notorious zoonotic C.
      pseudotuberculosis secretes sphingomyelinase (SMase) D, a phospholipase that
      cleaves off the choline moiety of sphingomyelin, a phospholipid found primarily
      in the outer leaflet of host cell plasma membranes. Experimental C.
      pseudotuberculosis strains that lack SMase D are markedly less infectious and
      unable to spread in hosts, indicating that this enzyme is a crucial virulence
      factor for sustaining the caseous lymphadenitis infections caused by this
      microbe. However, the molecular mechanism by which SMase D helps bacteria evade
      the host's immune response remains unknown. Here, we find that SMase D inhibits
      store-operated Ca(2+) entry (SOCE) in human T cells and lowers the production of
      the SOCE-dependent cytokines interleukin-2, which is critical for T cell growth,
      proliferation, and differentiation, and tumor necrosis factor alpha, which is
      crucial for the formation and maintenance of granulomas in microbial infections.
      SMase D inhibits SOCE through a previously unknown mechanism, namely, suppression
      of Orai1 current, rather than through altering gating of voltage-gated K(+)
      channels. This finding suggests that, whereas certain genetic mutations abolish
      Orai1 activity causing severe combined immunodeficiency (SCID), bacteria have the
      ability to suppress Orai1 activity with SMase D to create an acquired, chronic
      SCID-like condition that allows persistent infection. Thus, in an example of how
      virulence factors can disrupt key membrane protein function by targeting
      phospholipids in host cell membranes, our study has uncovered a novel molecular
      mechanism that bacteria can use to thwart host immunity. 

PMID- 26216861
TI  - Identification of two clusters within schizophrenia with different structural,
      functional and clinical characteristics.
AB  - BACKGROUND: Several biologically distinct subgroups may coexist within
      schizophrenia, which may hamper the necessary replicability to translate research
      findings into clinical practice. METHODS: Cortical thickness, curvature and area
      values and subcortical volumes of 203 subjects (121 schizophrenia patients, out
      of which 64 were first episodes), 60 healthy controls and 22 bipolar patients
      were used to identify clusters using principal components and canonical
      discriminant analyses. Regional glucose metabolism using positron emission
      tomography, P300 event related potential, baseline clinical data and percentage
      of improvement with treatment were used to validate possible clusters based on
      MRI data. RESULTS: All the controls, the bipolar patients and most of the
      schizophrenia patients were grouped in a cluster (cluster A). A group of 24
      schizophrenia patients (12 first episodes), characterized by large intrinsic
      curvature values, was identified (cluster B). These patients, but not those in
      cluster A, showed reduced thalamic and cingulate glucose metabolism in comparison
      to controls, as well as a worsening of negative symptoms at follow-up. Patients
      in cluster A showed a significant putaminal metabolic increase, which was not
      observed for those in cluster B. P300 amplitude was reduced in patients of both
      clusters, in comparison to controls. CONCLUSIONS: Results of this study support
      the existence of a biologically distinct group within the schizophrenia syndrome,
      characterized by increased cortical curvature values, reduced thalamic and
      cingulate metabolism, lack of the expected increased putaminal metabolism with
      antipsychotics and persistent negative symptoms.

PMID- 26216862
TI  - Therapeutic potential of cannabis-related drugs.
AB  - In this review, I will consider the dual nature of Cannabis and cannabinoids. The
      duality arises from the potential and actuality of cannabinoids in the laboratory
      and clinic and the 'abuse' of Cannabis outside the clinic. The therapeutic areas
      currently best associated with exploitation of Cannabis-related medicines include
      pain, epilepsy, feeding disorders, multiple sclerosis and glaucoma. As with every
      other medicinal drug of course, the 'trick' will be to maximise the benefit and
      minimise the cost. After millennia of proximity and exploitation of the Cannabis
      plant, we are still playing catch up with an understanding of its potential
      influence for medicinal benefit. 

PMID- 26216863
TI  - Heart rate variability in major depressive disorder and after antidepressant
      treatment with agomelatine and paroxetine: Findings from the Taiwan Study of
      Depression and Anxiety (TAISDA).
AB  - Evidence from previous studies suggests that heart rate variability (HRV) is
      reduced in major depressive disorder (MDD). However, whether this reduction is
      attributable to the disorder per se or to medication, since antidepressants may
      also affect HRV, is still debated. There is a dearth of information regarding the
      effects of agomelatine, a novel antidepressant, on HRV. Here, we investigated
      whether HRV is reduced in MDD and compared the effects of agomelatine and
      paroxetine on HRV. We recruited 618 physically healthy unmedicated patients with
      MDD and 506 healthy volunteers aged 20-65 years. Frequency-domain measures of
      resting HRV were obtained at the time of enrollment for all participants. For
      patients with MDD, these measures were obtained again after 6 weeks of either
      agomelatine or paroxetine monotherapy. Compared with healthy subjects,
      unmedicated patients with MDD exhibited significantly lower variance (total HRV),
      low frequency (LF), and high frequency (HF) HRV, and a higher LF/HF ratio.
      Depression severity independently contributed to decreased HRV and vagal tone.
      Fifty-six patients completed the open-label trial (n=29 for agomelatine, n=27 for
      paroxetine). Between-group analyses showed a significant group-by-time
      interaction for LF-HRV and HF-HRV, driven by increases in LF-HRV and HF-HRV only
      after agomelatine treatment. Within the paroxetine-treated group, there were no
      significant changes in mean R-R intervals or any HRV indices. We therefore
      concluded that MDD is associated with reduced HRV, which is inversely related to
      depression severity. Compared with paroxetine, agomelatine has a more vagotonic
      effect, suggesting greater cardiovascular safety. Clinicians should consider HRV
      effects while selecting antidepressants especially for depressed patients who
      already have decreased cardiac vagal tone.

PMID- 26216864
TI  - Can migraine be defined?

PMID- 26216865
TI  - Dyskinesias and impulse control disorders in Parkinson's disease: From
      pathogenesis to potential therapeutic approaches.
AB  - Dopaminergic treatment in Parkinson's disease (PD) reduces the severity of motor
      symptoms of the disease. However, its chronic use is associated with disabling
      motor and behavioral side effects, among which levodopa-induced dyskinesias (LID)
      and impulse control disorders (ICD) are the most common. The underlying
      mechanisms and pathological substrate of these dopaminergic complications are not
      fully understood. Recently, the refinement of imaging techniques and the study of
      the genetics and molecular bases of LID and ICD indicate that, although
      different, they could share some features. In addition, animal models of
      parkinsonism with LID have provided important knowledge about mechanisms
      underlying such complications. In contrast, animal models of parkinsonism and
      abnormal impulsivity, although useful regarding some aspects of human ICD, do not
      fully resemble the clinical phenotype of ICD in patients with PD, and until now
      have provided limited information. Studies on animal models of addiction could
      complement the previous models and provide some insights into the background of
      these behavioral complications given that ICD are regarded as behavioral
      addictions. Here we review the most relevant advances in relation to imaging,
      genetics, biochemistry and pharmacological interventions to treat LID and ICD in
      patients with PD and in animal models with a view to better understand the
      overlapping and unique maladaptations to dopaminergic therapy that are associated
      with LID and ICD. 

PMID- 26216867
TI  - Usefulness of cervical root magnetic stimulation in assessing proximal motor
      nerve conduction.
AB  - OBJECTIVES: To evaluate the reliability and utility of cervical root magnetic
      stimulation in exploring proximal motor conduction. METHODS: In 20 patients with
      demyelinating polyneuropathy (DPN), 20 patients with amyotrophic lateral
      sclerosis (ALS) and 25 healthy subjects, evoked compound muscle action potentials
      (CMAPs) were recorded from abductor digiti minimi muscle in response to
      electrical stimulation up to Erb's point and magnetic stimulation up to the
      cervical roots. RESULTS: In all healthy and ALS subjects, magnetic root
      stimulation confirmed the absence of conduction abnormalities, including those in
      whom supramaximal responses at Erb's point were not achieved. In the DPN group,
      conduction block and/or temporal dispersion was revealed by magnetic root
      stimulation in 9 out of 20 patients (45%), 3 more than those detected at Erb's
      point. CONCLUSIONS: Cervical root stimulation allowed clear distinction between
      motor neuronopathy and DPN. It is recommended as part of the routine evaluation
      of patients suspected of having DPN, especially when distal nerve studies are
      inconclusive.

PMID- 26216866
TI  - [Aplastic anemia: Current state of diagnosis and treatment].
AB  - Aplastic anemia (AAI) is a rare life-threatening disorder which is characterized
      by bi- or tricytopenia and hypoplastic or aplastic bone marrow. AA can present as
      an acquired or congenital disorder. In recent years it was noted that a subgroup
      of patients with seemingly acquired AA with onset in adulthood carry mutations
      which cause or at least predispose to bone marrow failure, e.g. mutations in the
      genes of the telomerase complex. Options for first-line treatment are allogeneic
      stem cell transplantation or immunosuppression. The decision depends on severity
      of the disease, age and comorbidity of the patient and availability of a matched
      stem cell donor. Probability of survival after HLA-identical sibling
      transplantation exceeds 90% in young patients with bone marrow as the stem cell
      source and conditioning with an ATG-containing regimen. Results of matched
      unrelated donor transplantation have improved substantially over the last 10
      years. Matched unrelated donor transplantation is increasingly considered as the
      first-line treatment for very young patients who are candidates for
      transplantation, but lack an HLA-identical sibling donor. The gold standard for
      immunosuppression is the combination of antithymocyte globulin (ATG) and
      cyclosporine A (CsA). ATG, a polyvalent antibody preparation, is obtained from
      animals after immunization with human thymocytes. Response rate and overall
      survival after horse ATG treatment are significantly higher compared to rabbit
      ATG. Recent trials reported a surprisingly high rate of bi- and trilinear
      response to treatment with the thrombopoietin receptor agonist eltrombopag in
      patients refractory to immunosuppression. Ongoing trials now address the
      potential role of eltrombopag as an adjunct to immunosuppression in first-line
      treatment.

PMID- 26216868
TI  - Trunk muscle coactivation is tuned to changes in task dynamics to improve
      responsiveness in a seated balance task.
AB  - When balancing, instability can occur when the object being balanced moves at a
      rate that is beyond the abilities of human motor control. This illustrates that
      responsiveness of motor control is limited and can be investigated by changing
      the dynamics of the task. In this study, the responsiveness of trunk motor
      control was investigated by changing the seat stiffness of an unstable seat. At
      decreasing levels of seat stiffness the probability of successfully balancing on
      the seat, speed of the seat, speed of the trunk relative to the seat (trunk-seat)
      and muscle activation of five trunk muscles were assessed. Also, across the
      different stiffness levels, the relation between trunk muscle activation and seat
      speed was determined. As hypothesized, with decreasing seat stiffness the
      probability of success decreased, seat speed and trunk-seat speed increased, and
      both agonist and antagonist activation increased. This shows that limits in the
      responsiveness of trunk motor control were reached during seated balancing.
      Furthermore, in line with our hypothesis, a positive relation was found between
      trunk muscle activation and seat speed. It appears that the central nervous
      system regulates trunk stiffness (via muscle coactivation) in relation to the
      dynamics of the task, possibly to maintain adequate responsiveness. 

PMID- 26216869
TI  - An evaluation of fundus photography and fundus autofluorescence in the diagnosis
      of cuticular drusen.
AB  - PURPOSE: To examine non-mydriatic fundus photography (FP) and fundus
      autofluorescence (FAF) as alternative non-invasive imaging modalities to
      fluorescein angiography (FA) in the detection of cuticular drusen (CD). METHODS:
      Among 2953 adults from the Danish Rural Eye Study (DRES) with gradable FP, three
      study groups were selected: (1) All those with suspected CD without age-related
      macular degeneration (AMD) on FP, (2) all those with suspected CD with AMD on FP
      and (3) a randomly selected group with early AMD. Groups 1, 2 and 3 underwent FA
      and FAF and group 4 underwent FAF only as part of DRES CD substudy. Main outcome
      measures included percentage of correct positive and correct negative diagnoses,
      Cohen's kappa and prevalence-adjusted and bias-adjusted kappa (PABAK)
      coefficients of test and grader reliability. RESULTS: CD was correctly identified
      on FP 88.9% of the time and correctly identified as not being present 83.3% of
      the time. CD was correctly identified on FAF 62.0% of the time and correctly
      identified as not being present 100.0% of the time. Compared with FA, FP has a
      PABAK of 0.75 (0.60 to 1.5) and FAF a PABAK of 0.44 (0.23 to 0.95). CONCLUSIONS:
      FP is a promising, non-invasive substitute for FA in the diagnosis of CD. FAF was
      less reliable than FP to detect CD.

PMID- 26216870
TI  - Frailty scoring in transcatheter aortic valve replacement patients.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a less invasive
      treatment option for patients that are deemed too high a risk for surgical aortic
      valve replacement (SAVR). The aim of this review is to evaluate the frailty tools
      currently being used in patients referred for TAVR. METHODS: Using a literature
      search involving database search engines from CINAHL, PubMed, SAGE publications
      and European Society of Cardiology conducted from 2010 to the present, a critical
      evaluation of studies dealing with frailty assessment in patients referred for
      TAVR/SAVR is discussed. RESULTS: Eight studies met the criteria using frailty
      assessment in TAVR/SAVR patients. In all reviewed studies the impact of frailty
      on clinical outcome has been proved. Different instruments for measurements of
      frailty were used that have not been robustly evaluated. Frailty was defined
      differently and results may not be comparable. All reviewed studies used
      different cutoffs and scales and some a composite scoring system, although
      validity was limited. CONCLUSION: For frailty assessment implementation of
      validated standardized test protocols based on well-established assessment tools,
      covering all domains of frailty among TAVR centers is crucial for patient
      selection. Secondly, validated cutoffs and scoring systems are essential.

PMID- 26216871
TI  - Injuries in national Olympic level judo athletes: an epidemiological study.
AB  - PURPOSE: To present an epidemiological study of injuries found among South
      Korea's National level Judo athletes as a foundation for future injury prevention
      and skill enhancement in this group. METHODS: This study is a prospective study
      on a 4-year injury assessment held from January 2010 to December 2013 at the
      training centre in South Korea for National Level athletes. Athlete's weight
      class, gender, injury location and injury grade (grade I=1-3 treatment days,
      grade II=4-7 treatment days, and grade III >=8 treatment days) were analysed.
      RESULTS: There were a total of 782 injuries recorded during this period,
      equalling to four injuries per athlete annually. Almost half of these injuries
      (47%) were grade I injuries. Injury occurrence was the highest in the Lower body
      (44.2%). This was then followed by injuries in the upper body (29.8%), trunk
      (20.3%) and head and neck (5.6%). Men and women showed similar, non-significantly
      different trends in the proportion of body parts injured. Women experienced more
      grade III injuries than males (p=0.0228). Comparison between women in different
      weight classes also showed that heavyweights incurred more grade III injuries
      than lightweights (p=0.0087). Lightweights had a higher rate of injury than
      heavyweights in males and females, although this was statistically significant
      only among males (p<0.001). CONCLUSIONS: Many body regions are prone to injury in
      the elite judo population. Women, especially those in the heavyweight
      classification, were more prone to severe injuries. Lightweights experienced more
      injuries than heavyweights among male athletes. Specifically, further studies are
      needed to confirm these findings and to address the impact of rapid weight loss
      practices on injury risk to implement effective preventive measures.

PMID- 26216872
TI  - A 5-Day-Old Late Preterm Infant With GBS Disease Despite Adequate Intrapartum
      Prophylaxis: Early or Late-Onset Disease?

PMID- 26216873
TI  - Risk of dementia in seniors with newly diagnosed diabetes: a population-based
      study.
AB  - OBJECTIVE: To study whether diabetes onset in late life is a risk factor for
      dementia. RESEARCH DESIGN AND METHODS: We conducted a population-based matched
      cohort study using provincial health data from Ontario, Canada. Seniors with (n =
      225,045) and without newly diagnosed diabetes (n = 668,070) between April 1995
      and March 2007 were followed until March 2012 for a new diagnosis of dementia.
      Cox proportional hazards modeling was used to compare the risk of dementia
      between groups after adjusting for baseline cardiovascular disease, chronic
      kidney disease (CKD), hypertension, and other risk factors. RESULTS: Over this
      period, we observed 169,114 new cases of dementia. Individuals with diabetes had
      a modestly higher incidence of dementia (2.68 vs. 2.62 per 100 person-years) than
      those without diabetes. In the fully adjusted Cox model, the risk of dementia was
      16% higher among our subgroup with diabetes (hazard ratio [HR] 1.16 [95% CI 1.15
      1.18]). Adjusted HRs for dementia were 1.20 (95% CI 1.17-1.22) and 1.14 (95% CI
      1.12-1.16) among men and women, respectively. Among seniors with diabetes, the
      risk of dementia was greatest in those with prior cerebrovascular disease (HR
      2.03; 95% CI 1.88-2.19), peripheral vascular disease (HR 1.47; 95% CI 1.19-1.82),
      and CKD (HR 1.44; 95% CI 1.38-1.51), and those with one or more hospital visits
      for hypoglycemia (HR 1.73; 95% CI 1.62-1.84). CONCLUSIONS: In this population
      based study, newly diagnosed diabetes was associated with a 16% increase in the
      risk of dementia among seniors. Preexisting vascular disease and severe
      hypoglycemia were the greatest risk factors for dementia in seniors with
      diabetes.

PMID- 26216874
TI  - Type 1 diabetes is associated with an increased risk of fracture across the life
      span: a population-based cohort study using The Health Improvement Network
      (THIN).
AB  - OBJECTIVE: This study was conducted to determine if type 1 diabetes is associated
      with an increased risk of fracture across the life span. RESEARCH DESIGN AND
      METHODS: This population-based cohort study used data from The Health Improvement
      Network (THIN) in the U.K. (data from 1994 to 2012), in which 30,394 participants
      aged 0-89 years with type 1 diabetes were compared with 303,872 randomly selected
      age-, sex-, and practice-matched participants without diabetes. Cox regression
      analysis was used to determine hazard ratios (HRs) for incident fracture in
      participants with type 1 diabetes. RESULTS: A total of 334,266 participants,
      median age 34 years, were monitored for 1.9 million person-years. HR were lowest
      in males and females age <20 years, with HR 1.14 (95% CI 1.01-1.29) and 1.35 (95%
      CI 1.12-1.63), respectively. Risk was highest in men 60-69 years (HR 2.18 [95% CI
      1.79-2.65]), and in women 40-49 years (HR 2.03 [95% CI 1.73-2.39]). Lower
      extremity fractures comprised a higher proportion of incident fractures in
      participants with versus those without type 1 diabetes (31.1% vs. 25.1% in males,
      39.3% vs. 32% in females; P < 0.001). Secondary analyses for incident hip
      fractures identified the highest HR of 5.64 (95% CI 3.55-8.97) in men 60-69 years
      and the highest HR of 5.63 (95% CI 2.25-14.11) in women 30-39 years. CONCLUSIONS:
      Type 1 diabetes was associated with increased risk of incident fracture that
      began in childhood and extended across the life span. Participants with type 1
      diabetes sustained a disproportionately greater number of lower extremity
      fractures. These findings have important public health implications, given the
      increasing prevalence of type 1 diabetes and the morbidity and mortality
      associated with hip fractures.

PMID- 26216877
TI  - Kinetic dissection of the pre-existing conformational equilibrium in the trypsin
      fold.
AB  - Structural biology has recently documented the conformational plasticity of the
      trypsin fold for both the protease and zymogen in terms of a pre-existing
      equilibrium between closed (E*) and open (E) forms of the active site region. How
      such plasticity is manifested in solution and affects ligand recognition by the
      protease and zymogen is poorly understood in quantitative terms. Here we dissect
      the E*-E equilibrium with stopped-flow kinetics in the presence of excess ligand
      or macromolecule. Using the clotting protease thrombin and its zymogen precursor
      prethrombin-2 as relevant models we resolve the relative distribution of the E*
      and E forms and the underlying kinetic rates for their interconversion. In the
      case of thrombin, the E* and E forms are distributed in a 1:4 ratio and
      interconvert on a time scale of 45 ms. In the case of prethrombin-2, the
      equilibrium is shifted strongly (10:1 ratio) in favor of the closed E* form and
      unfolds over a faster time scale of 4.5 ms. The distribution of E* and E forms
      observed for thrombin and prethrombin-2 indicates that zymogen activation is
      linked to a significant shift in the pre-existing equilibrium between closed and
      open conformations that facilitates ligand binding to the active site. These
      findings broaden our mechanistic understanding of how conformational transitions
      control ligand recognition by thrombin and its zymogen precursor prethrombin-2
      and have direct relevance to other members of the trypsin fold. 

PMID- 26216878
TI  - Divergent roles of CAAX motif-signaled posttranslational modifications in the
      regulation and subcellular localization of Ral GTPases.
AB  - The Ras-like small GTPases RalA and RalB are well validated effectors of RAS
      oncogene-driven human cancer growth, and pharmacologic inhibitors of Ral function
      may provide an effective anti-Ras therapeutic strategy. Intriguingly, although
      RalA and RalB share strong overall amino acid sequence identity, exhibit
      essentially identical structural and biochemical properties, and can utilize the
      same downstream effectors, they also exhibit divergent and sometimes opposing
      roles in the tumorigenic and metastatic growth of different cancer types. These
      distinct biological functions have been attributed largely to sequence divergence
      in their carboxyl-terminal hypervariable regions. However, the role of
      posttranslational modifications signaled by the hypervariable region carboxyl
      terminal tetrapeptide CAAX motif (C = cysteine, A = aliphatic amino acid, X =
      terminal residue) in Ral isoform-selective functions has not been addressed. We
      determined that these modifications have distinct roles and consequences. Both
      RalA and RalB require Ras converting CAAX endopeptidase 1 (RCE1) for association
      with the plasma membrane, albeit not with endomembranes, and loss of RCE1 caused
      mislocalization as well as sustained activation of both RalA and RalB. In
      contrast, isoprenylcysteine carboxylmethyltransferase (ICMT) deficiency disrupted
      plasma membrane localization only of RalB, whereas RalA depended on ICMT for
      efficient endosomal localization. Furthermore, the absence of ICMT increased
      stability of RalB but not RalA protein. Finally, palmitoylation was critical for
      subcellular localization of RalB but not RalA. In summary, we have identified
      striking isoform-specific consequences of distinct CAAX-signaled
      posttranslational modifications that contribute to the divergent subcellular
      localization and activity of RalA and RalB. 

PMID- 26216881
TI  - Muscle glycogen remodeling and glycogen phosphate metabolism following exhaustive
      exercise of wild type and laforin knockout mice.
AB  - Glycogen, the repository of glucose in many cell types, contains small amounts of
      covalent phosphate, of uncertain function and poorly understood metabolism. Loss
      of-function mutations in the laforin gene cause the fatal neurodegenerative
      disorder, Lafora disease, characterized by increased glycogen phosphorylation and
      the formation of abnormal deposits of glycogen-like material called Lafora
      bodies. It is generally accepted that the phosphate is removed by the laforin
      phosphatase. To study the dynamics of skeletal muscle glycogen phosphorylation in
      vivo under physiological conditions, mice were subjected to glycogen-depleting
      exercise and then monitored while they resynthesized glycogen. Depletion of
      glycogen by exercise was associated with a substantial reduction in total
      glycogen phosphate and the newly resynthesized glycogen was less branched and
      less phosphorylated. Branching returned to normal on a time frame of days,
      whereas phosphorylation remained suppressed over a longer period of time. We
      observed no change in markers of autophagy. Exercise of 3-month-old laforin knock
      out mice caused a similar depletion of glycogen but no loss of glycogen
      phosphate. Furthermore, remodeling of glycogen to restore the basal branching
      pattern was delayed in the knock-out animals. From these results, we infer that
      1) laforin is responsible for glycogen dephosphorylation during exercise and acts
      during the cytosolic degradation of glycogen, 2) excess glycogen phosphorylation
      in the absence of laforin delays the normal remodeling of the branching
      structure, and 3) the accumulation of glycogen phosphate is a relatively slow
      process involving multiple cycles of glycogen synthesis-degradation, consistent
      with the slow onset of the symptoms of Lafora disease. 

PMID- 26216882
TI  - Regulation of RNF144A E3 Ubiquitin Ligase Activity by Self-association through
      Its Transmembrane Domain.
AB  - RNF144A, an E3 ubiquitin ligase for DNA-dependent protein kinase catalytic
      subunit (DNA-PKcs), can promote DNA damage-induced cell apoptosis. Here we
      characterize an important regulation of RNF144A through its transmembrane (TM)
      domain. The TM domain of RNF144A is highly conserved among species. Deletion of
      the TM domain abolishes its membrane localization and also significantly reduces
      its ubiquitin ligase activity. Further evidence shows that the TM domain is
      required for RNF144A self-association and that the self-association may be
      partially mediated through a classic GXXXG interaction motif. A mutant RNF144A
      G252L/G256L (in the G(252)XXXG(256) motif) preserves membrane localization but is
      defective in self-association and ubiquitin ligase activity. On the other hand, a
      membrane localization loss mutant of RNF144A still retains self-association and
      E3 ligase activity, which can be blocked by additional G252L/G256L mutations.
      Therefore, our data demonstrate that the TM domain of RNF144A has at least two
      independent roles, membrane localization and E3 ligase activation, to regulate
      its physiological function. This regulatory mechanism may be applicable to other
      RBR (RING1-IBR-RING2) E3 ubiquitin ligases because, first, RNF144B also self
      associates. Second, all five TM-containing RBR E3 ligases, including RNF144A and
      RNF144B, RNF19A/Dorfin, RNF19B, and RNF217, have the RBR-TM(GXXXG)
      superstructure. Mutations of the GXXXG motifs in RNF144A and RNF217 have also be
      found in human cancers, including a G252D mutation of RNF144A. Interestingly,
      RNF144A-G252D still preserves self-association and ubiquitin ligase activity but
      loses membrane localization and is turned over rapidly. In conclusion, both
      proper membrane localization and self-association are important for RNF144A
      function. 

PMID- 26216880
TI  - Dual targeting of the chemokine receptors CXCR4 and ACKR3 with novel engineered
      chemokines.
AB  - The chemokine CXCL12 and its G protein-coupled receptors CXCR4 and ACKR3 are
      implicated in cancer and inflammatory and autoimmune disorders and are targets of
      numerous antagonist discovery efforts. Here, we describe a series of novel, high
      affinity CXCL12-based modulators of CXCR4 and ACKR3 generated by selection of N
      terminal CXCL12 phage libraries on live cells expressing the receptors. Twelve of
      13 characterized CXCL12 variants are full CXCR4 antagonists, and four have Kd
      values <5 nm. The new variants also showed high affinity for ACKR3. The variant
      with the highest affinity for CXCR4, LGGG-CXCL12, showed efficacy in a murine
      model for multiple sclerosis, demonstrating translational potential. Molecular
      modeling was used to elucidate the structural basis of binding and antagonism of
      selected variants and to guide future designs. Together, this work represents an
      important step toward the development of therapeutics targeting CXCR4 and ACKR3. 

PMID- 26216879
TI  - Galectin-1 regulates tissue exit of specific dendritic cell populations.
AB  - During inflammation, dendritic cells emigrate from inflamed tissue across the
      lymphatic endothelium into the lymphatic vasculature and travel to regional lymph
      nodes to initiate immune responses. However, the processes that regulate
      dendritic cell tissue egress and migration across the lymphatic endothelium are
      not well defined. The mammalian lectin galectin-1 is highly expressed by vascular
      endothelial cells in inflamed tissue and has been shown to regulate immune cell
      tissue entry into inflamed tissue. Here, we show that galectin-1 is also highly
      expressed by human lymphatic endothelial cells, and deposition of galectin-1 in
      extracellular matrix selectively regulates migration of specific human dendritic
      cell subsets. The presence of galectin-1 inhibits migration of immunogenic
      dendritic cells through the extracellular matrix and across lymphatic endothelial
      cells, but it has no effect on migration of tolerogenic dendritic cells. The
      major galectin-1 counter-receptor on both dendritic cell populations is the cell
      surface mucin CD43; differential core 2 O-glycosylation of CD43 between
      immunogenic dendritic cells and tolerogenic dendritic cells appears to contribute
      to the differential effect of galectin-1 on migration. Binding of galectin-1 to
      immunogenic dendritic cells reduces phosphorylation and activity of the protein
      tyrosine kinase Pyk2, an effect that may also contribute to reduced migration of
      this subset. In a murine lymphedema model, galectin-1(-/-) animals had increased
      numbers of migratory dendritic cells in draining lymph nodes, specifically
      dendritic cells with an immunogenic phenotype. These findings define a novel role
      for galectin-1 in inhibiting tissue emigration of immunogenic, but not
      tolerogenic, dendritic cells, providing an additional mechanism by which galectin
      1 can dampen immune responses. 

PMID- 26216884
TI  - Contribution of Lateral Column Lengthening to Correction of Forefoot Abduction in
      Stage IIb Adult Acquired Flatfoot Deformity Reconstruction.
AB  - BACKGROUND: Correction of forefoot abduction in stage IIb adult acquired flatfoot
      likely depends on the amount of lateral column lengthening (LCL) performed,
      although this represents only one aspect of a successful reconstruction. The
      purpose of this study was to evaluate the correlation between common
      reconstructive variables and the observed change in forefoot abduction. METHODS:
      Forty-one patients who underwent flatfoot reconstruction involving an Evans-type
      LCL were assessed retrospectively. Preoperative and postoperative anteroposterior
      (AP) radiographs of the foot at a minimum of 40 weeks (mean, 2 years) after
      surgery were reviewed to determine correction in forefoot abduction as measured
      by talonavicular coverage (TNC) angle, talonavicular uncoverage percent, talus
      first metatarsal (T-1MT) angle, and lateral incongruency angle. Fourteen
      demographic and intraoperative variables were evaluated for association with
      change in forefoot abduction including age, gender, height, weight, body mass
      index, as well as the amount of LCL and medializing calcaneal osteotomy
      performed, LCL graft type, Cotton osteotomy, first tarsometatarsal fusion, flexor
      digitorum longus transfer, spring ligament repair, gastrocnemius recession and
      any one of the modified McBride/Akin/Silver procedures. RESULTS: Two variables
      significantly affected the change in lateral incongruency angle. These were
      weight (P = .04) and the amount of LCL performed (P < .001). No variables were
      associated with the change in TNC angle, talonavicular uncoverage percent, or T
      1MT angle. Multivariate regression analysis revealed that LCL was the only
      significant predictor of the change in lateral incongruency angle. The final
      regression model for LCL showed a good fit (R2 = 0.70, P < .001). Each millimeter
      of LCL corresponded to a 6.8-degree change in lateral incongruency angle.
      CONCLUSION: Correction of forefoot abduction in flatfoot reconstruction was
      primarily determined by the LCL procedure and could be modeled linearly. We
      believe that the lateral incongruency angle can serve as a valuable preoperative
      measurement to help surgeons titrate the proper amount of correction performed
      intraoperatively.

PMID- 26216883
TI  - Complementary roles of specific cysteines in keratin 14 toward the assembly,
      organization, and dynamics of intermediate filaments in skin keratinocytes.
AB  - We recently showed that inter-keratin disulfide bonding plays an important role
      in the assembly, organization, and dynamics of keratin intermediate filaments in
      skin keratinocytes. In particular, cysteine 367 located in the central alpha
      helical rod domain of keratin 14 is necessary for the formation of a stable
      perinuclear network of keratin filaments (with type II partner keratin 5) in skin
      keratinocytes analyzed by static and live cell imaging. Here, we show that two
      additional cysteine residues located in the non-helical head domain of K14, Cys-4
      and Cys-40, also participate in inter-keratin disulfide bonding and tandemly play
      a key role complementary to that of Cys-367 in the assembly, organization, and
      dynamics of keratin filaments in skin keratinocytes in primary culture. Analysis
      of K14 variants with single or multiple substitutions of cysteine residues points
      to a spatial and temporal hierarchy in how Cys-4/Cys-40 and Cys-367 regulate
      keratin assembly in vitro and filament dynamics in live keratinocytes in culture.
      Our findings substantiate the importance and complexity of a novel determinant,
      namely inter-keratin disulfide bonding, for the regulation of several aspects of
      keratin filaments in surface epithelia. 

PMID- 26216885
TI  - Association between Drug-Induced Sleep Endoscopy and Measures of Sleep Apnea
      Burden.
AB  - OBJECTIVE: To test the following associations: (1) complete obstruction on drug
      induced sleep endoscopy (DISE) and polysomnographic and subjective measures of
      obstructive sleep apnea; (2) tongue base/epiglottic obstruction and apnea index.
      STUDY DESIGN: Retrospective cohort. SETTING: Academic medical center. SUBJECTS
      AND METHODS: Subjects included surgically naive adult patients with DISE. Chart
      extraction included demographics, polysomnography, and Epworth Sleepiness Scale
      and SNORE25 (Symptoms of Nocturnal Obstruction and Related Events 25) scores.
      Each DISE video was examined for complete obstruction at velum, oropharynx,
      tongue, epiglottis (VOTE system). Student's t test, correlation, and multivariate
      linear regression were performed. RESULTS: Among 65 subjects, complete
      obstruction was observed at 0 (3%), 1 (46%), 2 (48%), and 3 (3%) subsites,
      respectively. Subjects with 0-1 subsites vs 2-4 subsites of complete obstruction
      had similar apnea indexes (13 +/- 24 vs 12 +/- 17, P = .78, 83% power to detect
      difference of 15), apnea-hypopnea indexes (30 +/- 25 vs 31 +/- 28, P = .96, 54%
      power to detect difference of 15), Epworth Sleepiness Scale scores (11 +/- 7 vs
      12 +/- 5, P = .34, 91% power to detect difference of 5), and SNORE25 scores (2.0
      +/- 1.1 vs 1.9 +/- 1.0, P = .70, 96% power to detect difference of 1.0), with
      similar results after adjusting for age, sex, body mass index, and tonsil status.
      Neither tongue base nor epiglottic obstruction was associated with apnea index.
      CONCLUSION: The number of subsites with complete obstruction on DISE was not
      associated with polysomnographic, subjective sleepiness, and quality-of-life
      measures. Tongue base and epiglottic obstruction were not associated with apnea
      index. Larger detailed analyses are needed to determine the importance of each
      site and degree of obstruction seen on DISE.

PMID- 26216886
TI  - Cost-Benefit Analysis of an Otolaryngology Emergency Room Using a Contingent
      Valuation Approach.
AB  - OBJECTIVES: Dedicated otolaryngology emergency rooms (ERs) provide a unique
      mechanism of health care delivery. Relative costs and willingness to pay (WTP)
      for these services have not been studied. This study aims to provide a cost
      benefit analysis of otolaryngology-specific ER care. STUDY DESIGN: Cost-benefit
      analysis based on contingent valuation surveys. SETTING: An otolaryngology
      specific ER in a tertiary care academic medical center. SUBJECTS AND METHODS:
      Adult English-speaking patients presenting to an otolaryngology ER were included.
      WTP questions were used to assess patient valuations of specialty emergency care.
      Sociodemographic data, income, and self-reported levels of distress were
      assessed. State-level and institution-specific historical cost data were merged
      with WTP data within a cost-benefit analysis framework. RESULTS: The response
      rate was 75.6%, and 199 patients were included in the final analysis. Average WTP
      for otolaryngology ER services was $319 greater than for a general ER (95% CI:
      $261 to $377), with a median value of $200. The historical mean cost per visit at
      a general ER was $575, and mean cost at the specialty ER was $551 (95% CI: $529
      to $574). Subtracting incremental cost from incremental WTP yielded a net benefit
      of $343. CONCLUSION: Dedicated otolaryngology ER services are valued by patients
      for acute otolaryngologic problems and have a net benefit of $343 per patient
      visit. They appear to be a cost-beneficial method for addressing acute
      otolaryngologic conditions. This study has implications for ER-based
      otolaryngologic care and direct-to-specialist services.

PMID- 26216887
TI  - Sensorineural Hearing Loss: A Changing Paradigm for Its Evaluation.
AB  - OBJECTIVE: To determine how practicing clinicians evaluate patients with
      sensorineural hearing loss (SNHL) and to analyze the cost-effectiveness of
      current algorithms in the evaluation of these patients. STUDY DESIGN/SETTING: An
      interactive online survey allowing respondents to order diagnostic testing in the
      evaluation of 4 simulated patients with SNHL across 2 testing encounters per
      patient. SUBJECTS AND METHODS: The survey was distributed to clinician members of
      the American Society of Pediatric Otolaryngology and the American Society of
      Human Genetics between May and August 2014. Statistical tests included chi-square
      and nonparametric testing with Mann-Whitney U test. RESULTS: Otolaryngologists
      were significantly more likely than other clinicians to order repeat audiometric
      testing and significantly less likely to order genetic testing. Respondents who
      completed training more recently were significantly more likely to order magnetic
      resonance imaging and electrocardiogram. On average, respondents spent $4756 in
      the evaluation of a single patient, with otolaryngologists spending significantly
      more than other clinicians. Computed tomography of the temporal bone (40%),
      ophthalmology consultation (39%), and genetics consultation (37%) were ordered
      most frequently in the first encounter. Comprehensive genetic testing was ordered
      least frequently on the first encounter (20%) but was the most frequently ordered
      test on the second encounter (30%). CONCLUSION: Recent guidelines advocate
      comprehensive genetic testing in the evaluation of patients with SNHL, as early
      genetic testing can prevent uninformative additional tests that otherwise
      increase health care expenditures. Results from this survey indicate that
      comprehensive genetic testing is now frequently but not uniformly included in
      evaluation of patients with SNHL.

PMID- 26216888
TI  - IL-15 Superagonist-Mediated Immunotoxicity: Role of NK Cells and IFN-gamma.
AB  - IL-15 is currently undergoing clinical trials to assess its efficacy for
      treatment of advanced cancers. The combination of IL-15 with soluble IL-15Ralpha
      generates a complex termed IL-15 superagonist (IL-15 SA) that possesses greater
      biological activity than IL-15 alone. IL-15 SA is considered an attractive
      antitumor and antiviral agent because of its ability to selectively expand NK and
      memory CD8(+) T (mCD8(+) T) lymphocytes. However, the adverse consequences of IL
      15 SA treatment have not been defined. In this study, the effect of IL-15 SA on
      physiologic and immunologic functions of mice was evaluated. IL-15 SA caused dose
      and time-dependent hypothermia, weight loss, liver injury, and mortality. NK
      (especially the proinflammatory NK subset), NKT, and mCD8(+) T cells were
      preferentially expanded in spleen and liver upon IL-15 SA treatment. IL-15 SA
      caused NK cell activation as indicated by increased CD69 expression and IFN
      gamma, perforin, and granzyme B production, whereas NKT and mCD8(+) T cells
      showed minimal, if any, activation. Cell depletion and adoptive transfer studies
      showed that the systemic toxicity of IL-15 SA was mediated by hyperproliferation
      of activated NK cells. Production of the proinflammatory cytokine IFN-gamma, but
      not TNF-alpha or perforin, was essential to IL-15 SA-induced immunotoxicity. The
      toxicity and immunological alterations shown in this study are comparable to
      those reported in recent clinical trials of IL-15 in patients with refractory
      cancers and advance current knowledge by providing mechanistic insights into IL
      15 SA-mediated immunotoxicity.

PMID- 26216889
TI  - Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive
      Polymer-Based Adjuvant Systems.
AB  - The development of an anti-influenza vaccine with the potential for cross
      protection against seasonal drift variants as well as occasionally emerging
      reassortant viruses is essential. In this study, we successfully generated a
      novel anti-influenza vaccine system combining conserved matrix protein 2 (sM2)
      and stalk domain of hemagglutinin (HA2) fusion protein (sM2HA2) and poly-gamma
      glutamic acid (gamma-PGA)-based vaccine adjuvant systems that can act as a
      mucoadhesive delivery vehicle of sM2HA2 as well as a robust strategy for the
      incorporation of hydrophobic immunostimulatory 3-O-desacyl-4'-monophosphoryl
      lipid A (MPL) and QS21. Intranasal coadministration of sM2HA2 and the combination
      adjuvant gamma-PGA/MPL/QS21 (CA-PMQ) was able to induce a high degree of
      protective mucosal, systemic, and cell-mediated immune responses. The sM2HA2/CA
      PMQ immunization was able to prevent disease symptoms, confering complete
      protection against lethal infection with divergent influenza subtypes (H5N1,
      H1N1, H5N2, H7N3, and H9N2) that lasted for at least 6 mo. Therefore, our data
      suggest that mucosal administration of sM2HA2 in combination with CA-PMQ could be
      a potent strategy for a broad cross-protective influenza vaccine, and CA-PMQ as a
      mucosal adjuvant could be used for effective mucosal vaccines.

PMID- 26216890
TI  - Cattle NK Cell Heterogeneity and the Influence of MHC Class I.
AB  - Primate and rodent NK cells form highly heterogeneous lymphocyte populations
      owing to the differential expression of germline-encoded receptors. Many of these
      receptors are polymorphic and recognize equally polymorphic determinants of MHC
      class I. This diversity can lead to individuals carrying NK cells with different
      specificities. Cattle have an unusually diverse repertoire of NK cell receptor
      genes predicted to encode receptors that recognize MHC class I. To begin to
      examine whether this genetic diversity leads to a diverse NK cell population, we
      isolated peripheral NK cells from cattle with different MHC homozygous genotypes.
      Cytokine stimulation differentially influenced the transcription of five
      receptors at the cell population level. Using dilution cultures, we found that a
      further seven receptors were differentially transcribed, including five predicted
      to recognize MHC class I. Moreover, there was a statistically significant
      reduction in killer cell lectin-like receptor mRNA expression between cultures
      with different CD2 phenotypes and from animals with different MHC class I
      haplotypes. This finding confirms that cattle NK cells are a heterogeneous
      population and reveals that the receptors creating this diversity are influenced
      by the MHC. The importance of this heterogeneity will become clear as we learn
      more about the role of NK cells in cattle disease resistance and vaccination.

PMID- 26216891
TI  - IL-18 Is Involved in Eosinophil-Mediated Tumoricidal Activity against a Colon
      Carcinoma Cell Line by Upregulating LFA-1 and ICAM-1.
AB  - Eosinophils are multifunctional leukocytes that are involved in innate and
      adaptive immune responses through the expression of various receptors and
      mediators. Previously, we showed that human eosinophils and T cells shared
      cytotoxic activities against tumor cells that involved the gamma-delta TCR and
      cell-cell contact. In this study, we investigated the molecules involved in
      eosinophil-tumor cell interactions. Given the role of IL-18 in cell adhesion and
      in protecting against colon cancer, we evaluated its role in eosinophil-mediated
      cytotoxicity against Colo-205, a human colon carcinoma cell line. We found that
      human eosinophils exerted dose- and time-dependent tumoricidal activity against
      Colo-205 cells. Neutralization of IL-18 significantly reduced eosinophil-mediated
      Colo-205 apoptosis and inhibited cell-cell adhesion. Moreover, addition of rIL-18
      led to upregulation of CD11a and ICAM-1 adhesion molecules, which were involved
      in the contact between eosinophils and Colo-205 cells. Our results indicated that
      IL-18 was involved in the eosinophil-mediated death of Colo-205 by facilitating
      contact between effector and target cells. These data underscored the involvement
      of an additional mediator in eosinophil-mediated antitumor cytotoxicity. Our
      findings support existing evidence that eosinophils could play a beneficial role
      in the context of colon cancer.

PMID- 26216893
TI  - The Inflammatory Caspases-1 and -11 Mediate the Pathogenesis of Dermatitis in
      Sharpin-Deficient Mice.
AB  - Chronic proliferative dermatitis in mice (cpdm) is a spontaneous multiorgan
      inflammatory disorder with pathological hallmarks similar to atopic dermatitis
      and psoriasis in humans. Cpdm mice lack expression of SHANK-associated RH domain
      interacting protein, an adaptor of the linear ubiquitin assembly complex, which
      acts in the NF-kappaB pathway to promote inflammation and protect from apoptosis
      and necroptosis. Although skin inflammation in cpdm mice is driven by TNF- and
      RIPK1-induced cell death, the contribution of initiating innate immunity sensors
      and additional inflammatory pathways remains poorly characterized. In this
      article, we show that inflammasome signaling, including the expression and
      activation of the inflammatory caspase-1 and -11 and IL-1 family cytokines, was
      highly upregulated in the skin of cpdm mice prior to overt disease onset. Genetic
      ablation of caspase-1 and -11 from cpdm mice significantly reduced skin
      inflammation and delayed disease onset, whereas systemic immunological disease
      persisted. Loss of Nlrp3 also attenuated skin disease, albeit more variably.
      Strikingly, induction of apoptosis and necroptosis effectors was sharply
      decreased in the absence of caspase-1 and -11. These results position the
      inflammasome as an important initiating signal in skin disease pathogenesis and
      provide novel insights about inflammasome and cell death effector cross-talk in
      the context of inflammatory diseases.

PMID- 26216892
TI  - B Cell-Intrinsic IDO1 Regulates Humoral Immunity to T Cell-Independent Antigens.
AB  - Humoral responses to nonproteinaceous Ags (i.e., T cell independent [TI]) are a
      key component of the early response to bacterial and viral infection and a
      critical driver of systemic autoimmunity. However, mechanisms that regulate TI
      humoral immunity are poorly defined. In this study, we report that B cell
      intrinsic induction of the tryptophan-catabolizing enzyme IDO1 is a key mechanism
      limiting TI Ab responses. When Ido1(-/-) mice were immunized with TI Ags, there
      was a significant increase in Ab titers and formation of extrafollicular Ab
      secreting cells compared with controls. This effect was specific to TI Ags, as
      Ido1 disruption did not affect Ig production after immunization with protein Ags.
      The effect of IDO1 abrogation was confined to the B cell compartment, as adoptive
      transfer of Ido1(-/-) B cells to B cell-deficient mice was sufficient to
      replicate increased TI responses observed in Ido1(-/-) mice. Moreover, in vitro
      activation with TLR ligands or BCR crosslinking rapidly induced Ido1 expression
      and activity in purified B cells, and Ido1(-/-) B cells displayed enhanced
      proliferation and cell survival associated with increased Ig and cytokine
      production compared with wild-type B cells. Thus, our results demonstrate a
      novel, B cell-intrinsic, role for IDO1 as a regulator of humoral immunity that
      has implications for both vaccine design and prevention of autoimmunity.

PMID- 26216894
TI  - Repenser ensemble le concept d'autonomie alimentaire.
AB  - C'est au coeur du projet de recherche-action participative " Vers une autonomie
      alimentaire pour tou-te-s : agir et vivre ensemble le changement " (VAATAVEC) que
      s'est elaboree une definition nouvelle et evolutive de l'autonomie alimentaire.
      De ce projet regroupant des personnes en situation de pauvrete, chercheurs et
      intervenants, a emerge une conceptualisation resultant a la fois d'une methode de
      reflexion collective et d'un processus d'analyse collective, inspire de la
      theorisation ancree et de l'analyse conceptualisante de Paille et Mucchielli
      (2003). Le recours a l'expertise des personnes en situation de pauvrete, expertes
      du vecu de l'insecurite alimentaire, a contribue a ancrer cette definition dans
      les causes structurelles de l'insecurite alimentaire dans une perspective de
      developpement d'un pouvoir d'agir collectif, de toutes les personnes concernees.
      Il en resulte une definition de l'autonomie alimentaire d'ou ressort une
      contribution surtout methodologique et theorique.

PMID- 26216895
TI  - Strong, female and Black: Stereotypes of African Caribbean women's body shape and
      their effects on clinical encounters.
AB  - The aim of this article is to explore how tendencies to stereotype minority
      ethnic groups intersect with lay discourses about them in ways that can reproduce
      cultural prejudices and reinforce inequalities in access to services and health
      outcomes. Drawing upon Black feminist and cultural studies literature, we present
      a theoretical examination, the stereotypes of the Black woman as 'mammy' and
      'matriarch'. We suggest that the influence of these two images is central to
      understanding the normalisation of the larger Black female body within African
      Caribbean communities. This representation of excess weight contradicts
      mainstream negative discourses of large bodies that view it as a form of moral
      weakness. Seeking to stimulate reflection on how unacknowledged stereotypes may
      shape clinical encounters, we propose that for Black women, it is the perception
      of strength, tied into these racial images of 'mammy' and 'matriarch' which may
      influence when or how health services or advice are both sought by them and
      offered to them. This has particular significance in relation to how body weight
      and weight management are/are not talked about in primary care-based interactions
      and what support Black women are/are not offered. We argue that unintentional
      bias can have tangible impacts and health outcomes for Black women and possibly
      other minority ethnic groups.

PMID- 26216896
TI  - Personal health technologies, micropolitics and resistance: A new materialist
      analysis.
AB  - Personal health technologies are near-body devices or applications designed for
      use by a single individual, principally outside healthcare facilities. They
      enable users to monitor physiological processes or body activity, are frequently
      communication-enabled and sometimes also intervene therapeutically. This article
      explores a range of personal health technologies, from blood pressure or blood
      glucose monitors purchased in pharmacies and fitness monitors such as Fitbit and
      Nike+ Fuelband to drug pumps and implantable medical devices. It applies a new
      materialist analysis, first reverse engineering a range of personal health
      technologies to explore their micropolitics and then forward engineering personal
      health technologies to meet, variously, public health, corporate, patient and
      resisting-citizen agendas. This article concludes with a critical discussion of
      personal health technologies and the possibilities of designing devices and apps
      that might foster subversive micropolitics and encourage collective and resisting
      'citizen health'.

PMID- 26216897
TI  - Online self-expression and experimentation as 'reflectivism': Using text
      analytics to examine the participatory forum Hello Sunday Morning.
AB  - Hello Sunday Morning is an online health promotion organisation that began in
      2009. Hello Sunday Morning asks participants to stop consuming alcohol for a
      period of time, set a goal and document their progress on a personal blog. Hello
      Sunday Morning is a unique health intervention for three interrelated reasons:
      (1) it was generated outside a clinical setting, (2) it uses new media
      technologies to create structured forms of participation in an iterative and open
      ended way and (3) participants generate a written record of their progress along
      with demographic, behavioural and engagement data. This article presents a text
      analysis of the blog posts of Hello Sunday Morning participants using the
      software program Leximancer. Analysis of blogs illustrates how participants'
      expressions change over time. In the first month, participants tended to set
      goals, describe their current drinking practices in individual and cultural
      terms, express hopes and anxieties and report on early efforts to change. After
      month 1, participants continued to report on efforts to change and associated
      challenges and reflect on their place as individuals in a drinking culture. In
      addition to this, participants evaluated their efforts to change and presented
      their 'findings' and 'theorised' them to provide advice for others. We
      contextualise this text analysis with respect to Hello Sunday Morning's
      development of more structured forms of online participation. We offer a critical
      appraisal of the value of text analytics in the development of online health
      interventions.

PMID- 26216898
TI  - [L'effet et l'influence de l'espoir et de la surmediatisation sur la prise de
      decision en matiere de technologies de la sante].
AB  - La prise de decision en matiere de technologies de la sante est complexe. L'effet
      potentiel de l'espoir et de la surmediatisation est peu explore. Le present
      article traite de la commercialisation de l'espoir et de l'influence de sa
      surmediatisation sur la prise de decision. Puisque les leaders en sante jouent un
      role essentiel dans la prise de ce type de decisions, l'auteure traite egalement
      des possibilites et des suggestions liees a la structure des processus de
      decision afin de jeter un regard critique sur la " surmediatisation de l'espoir
      ". 

PMID- 26216899
TI  - SNAREs support atlastin-mediated homotypic ER fusion in Saccharomyces cerevisiae.
AB  - Dynamin-like GTPases of the atlastin family are thought to mediate homotypic
      endoplasmic reticulum (ER) membrane fusion; however, the underlying mechanism
      remains largely unclear. Here, we developed a simple and quantitative in vitro
      assay using isolated yeast microsomes for measuring yeast atlastin Sey1p
      dependent ER fusion. Using this assay, we found that the ER SNAREs Sec22p and
      Sec20p were required for Sey1p-mediated ER fusion. Consistently, ER fusion was
      significantly reduced by inhibition of Sec18p and Sec17p, which regulate SNARE
      mediated membrane fusion. The involvement of SNAREs in Sey1p-dependent ER fusion
      was further supported by the physical interaction of Sey1p with Sec22p and Ufe1p,
      another ER SNARE. Furthermore, our estimation of the concentration of Sey1p on
      isolated microsomes, together with the lack of fusion between Sey1p
      proteoliposomes even with a 25-fold excess of the physiological concentration of
      Sey1p, suggests that Sey1p requires additional factors to support ER fusion in
      vivo. Collectively, our data strongly suggest that SNARE-mediated membrane fusion
      is involved in atlastin-initiated homotypic ER fusion. 

PMID- 26216900
TI  - Endocytosis-dependent coordination of multiple actin regulators is required for
      wound healing.
AB  - The ability to heal wounds efficiently is essential for life. After wounding of
      an epithelium, the cells bordering the wound form dynamic actin protrusions
      and/or a contractile actomyosin cable, and these actin structures drive wound
      closure. Despite their importance in wound healing, the molecular mechanisms that
      regulate the assembly of these actin structures at wound edges are not well
      understood. In this paper, using Drosophila melanogaster embryos, we demonstrate
      that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating
      actin assembly during wound healing. Moreover, we show that endocytosis is
      essential for wound edge actin assembly and wound closure. We identify adherens
      junctions (AJs) as a key target of endocytosis during wound healing and propose
      that endocytic remodeling of AJs is required to form "signaling centers" along
      the wound edge that control actin assembly. We conclude that coordination of
      actin assembly, AJ remodeling, and membrane traffic is required for the
      construction of a motile leading edge during wound healing. 

PMID- 26216901
TI  - Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway.
AB  - The Hippo pathway is involved in the regulation of contact inhibition of
      proliferation and responses to various physical and chemical stimuli. Recently,
      several upstream negative regulators of Hippo signaling, including epidermal
      growth factor receptor ligands and lysophosphatidic acid, have been identified.
      We show that fibronectin adhesion stimulation of focal adhesion kinase (FAK)-Src
      signaling is another upstream negative regulator of the Hippo pathway. Inhibition
      of FAK or Src in MCF-10A cells plated at low cell density prevented the
      activation of Yes-associated protein (YAP) in a large tumor suppressor homologue
      (Lats)-dependent manner. Attachment of serum-starved MCF-10A cells to
      fibronectin, but not poly-d-lysine or laminin, induced YAP nuclear accumulation
      via the FAK-Src-phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) signaling
      pathway. Attenuation of FAK, Src, PI3K, or PDK1 activity blocked YAP nuclear
      accumulation stimulated by adhesion to fibronectin. This negative regulation of
      the Hippo pathway by fibronectin adhesion signaling can, at least in part,
      explain the effects of cell spreading on YAP nuclear localization and represents
      a Lats-dependent component of the response to cell adhesion. 

PMID- 26216902
TI  - A dynamic formin-dependent deep F-actin network in axons.
AB  - Although actin at neuronal growth cones is well-studied, much less is known about
      actin organization and dynamics along axon shafts and presynaptic boutons. Using
      probes that selectively label filamentous-actin (F-actin), we found focal "actin
      hotspots" along axons-spaced ~3-4 um apart-where actin undergoes continuous
      assembly/disassembly. These foci are a nidus for vigorous actin polymerization,
      generating long filaments spurting bidirectionally along axons-a phenomenon we
      call "actin trails." Super-resolution microscopy reveals intra-axonal deep actin
      filaments in addition to the subplasmalemmal "actin rings" described recently. F
      actin hotspots colocalize with stationary axonal endosomes, and blocking vesicle
      transport diminishes the actin trails, suggesting mechanistic links between
      vesicles and F-actin kinetics. Actin trails are formin-but not Arp2/3-dependent
      and help enrich actin at presynaptic boutons. Finally, formin inhibition
      dramatically disrupts synaptic recycling. Collectively, available data suggest a
      two-tier F-actin organization in axons, with stable "actin rings" providing
      mechanical support to the plasma membrane and dynamic "actin trails" generating a
      flexible cytoskeletal network with putative physiological roles.

PMID- 26216903
TI  - Lrrk regulates the dynamic profile of dendritic Golgi outposts through the golgin
      Lava lamp.
AB  - Constructing the dendritic arbor of neurons requires dynamic movements of Golgi
      outposts (GOPs), the prominent component in the dendritic secretory pathway. GOPs
      move toward dendritic ends (anterograde) or cell bodies (retrograde), whereas
      most of them remain stationary. Here, we show that Leucine-rich repeat kinase
      (Lrrk), the Drosophila melanogaster homologue of Parkinson's disease-associated
      Lrrk2, regulates GOP dynamics in dendrites. Lrrk localized at stationary GOPs in
      dendrites and suppressed GOP movement. In Lrrk loss-of-function mutants,
      anterograde movement of GOPs was enhanced, whereas Lrrk overexpression increased
      the pool size of stationary GOPs. Lrrk interacted with the golgin Lava lamp and
      inhibited the interaction between Lva and dynein heavy chain, thus disrupting the
      recruitment of dynein to Golgi membranes. Whereas overexpression of kinase-dead
      Lrrk caused dominant-negative effects on GOP dynamics, overexpression of the
      human LRRK2 mutant G2019S with augmented kinase activity promoted retrograde
      movement. Our study reveals a pathogenic pathway for LRRK2 mutations causing
      dendrite degeneration. 

PMID- 26216904
TI  - A Cross-sectional Study of the Association Between Chronic Hepatitis C Virus
      Infection and Subclinical Coronary Atherosclerosis Among Participants in the
      Multicenter AIDS Cohort Study.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection may increase the risk of
      cardiovascular disease (CVD). We evaluated the association of chronic HCV
      infection and coronary atherosclerosis among participants in the Multicenter AIDS
      Cohort Study. METHODS: We assessed 994 men with or without human immunodeficiency
      virus (HIV) infection (87 of whom had chronic HCV infection) for coronary plaque,
      using noncontrast coronary computed tomography (CT); 755 also underwent CT
      angiography. We then evaluated the associations of chronic HCV infection and HIV
      infection with measures of plaque prevalence, extent, and stenosis. RESULTS:
      After adjustment for demographic characteristics, HIV serostatus, behaviors, and
      CVD risk factors, chronic HCV infection was significantly associated with a
      higher prevalence of coronary artery calcium (prevalence ratio, 1.29; 95%
      confidence interval [CI], 1.02-1.63), any plaque (prevalence ratio, 1.26; 95% CI,
      1.09-1.45), and noncalcified plaque (prevalence ratio, 1.42; 95% CI, 1.16-1.75).
      Chronic HCV infection and HIV infection were independently associated with the
      prevalence of any plaque and of noncalcified plaque, but there was no evidence of
      a synergistic effect due to HIV/HCV coinfection. The prevalences of coronary
      artery calcium, any plaque, noncalcified plaque, a mixture of noncalcified and
      calcified plaque, and calcified plaque were significantly higher among men with
      an HCV RNA load of >=2 * 10(6) IU/mL, compared with findings among men without
      chronic HCV infection. CONCLUSIONS: Chronic HCV infection is associated with
      subclinical CVD, suggesting that vigilant assessments of cardiovascular risk are
      warranted for HCV-infected individuals. Future research should determine whether
      HCV infection duration or HCV treatment influence coronary plaque development.

PMID- 26216906
TI  - A template for a clinico-pathological audit of medical liver biopsies.
AB  - AIMS: With changing indications for performing medical liver biopsies, we aimed
      to develop a tool to allow pathologists to evaluate the current usefulness, value
      and impact of their medical liver biopsy service. METHODS: We designed and
      piloted a questionnaire-based clinico-pathological audit for medical liver
      biopsies. RESULTS: The audit tool was simple to implement and provided useful
      information about our service. Hepatologists felt that 96% of reports were
      clinically useful. 56% of biopsies confirmed clinical diagnoses, 46% helped
      differentiate between diagnoses and 42% were able to exclude possible diagnoses.
      74% resulted in a change of management and 27% of liver biopsies resulted in a
      diagnosis which was not clinically suspected. CONCLUSIONS: We demonstrate the
      usefulness of an audit tool in providing evidence of the value of the liver
      pathology service in a large UK regional centre.

PMID- 26216905
TI  - Hepatitis B Virus Pregenomic RNA Is Present in Virions in Plasma and Is
      Associated With a Response to Pegylated Interferon Alfa-2a and Nucleos(t)ide
      Analogues.
AB  - BACKGROUND: Treatment of patients with chronic hepatitis B (CHB) with
      nucleos(t)ide analogues (NAs) suppresses hepatitis B virus (HBV) DNA production
      but does not affect the synthesis of the RNA pregenome or HBV messenger RNA.
      Whether HBV RNA-containing particles continue to be secreted into the bloodstream
      remains controversial. METHODS: We developed a sensitive polymerase chain
      reaction (PCR) assay to quantify the HBV RNA load in a supernatant of NA-treated
      HepG2-2.2.15 cells and in plasma specimens from 20 patients with CHB who were
      receiving NA therapy and 86 patients treated with pegylated interferon alfa (Peg
      IFN) and adefovir. RESULTS: Treatment of HepG2-2.2.15 cells with NAs for 9 days
      reduced HBV DNA levels (by 1.98 log10 copies/mL), whereas HBV RNA levels
      increased (by 0.47 log10 copies/mL; P < .05). During long-term NA treatment of
      patients with CHB, HBV RNA levels remained higher than HBV DNA levels. Peg-IFN
      based treatment induced a stronger decrease in the HBV RNA load than NA
      monotherapy, and this decline was more pronounced in responders than in
      nonresponders. In HBV e antigen-negative patients, a lower baseline plasma HBV
      RNA level was independently associated with response to Peg-IFN and adefovir
      (odds ratio, 0.44; P = .019). Immunoprecipitation with HBV core antigen-specific
      antibodies after removal of the HBV surface antigen envelope demonstrated the
      association of plasma HBV RNA with virions. CONCLUSIONS: HBV RNA is present in
      virions in plasma specimens from patients with CHB. HBV RNA levels vary
      significantly from those of established viral markers during antiviral treatment,
      which highlights its potential as an independent marker in the evaluation of
      patients with CHB.

PMID- 26216907
TI  - Gene of the month: NANOG.

PMID- 26216908
TI  - In vitro differentiation of human amniotic epithelial cells into insulin
      producing 3D spheroids.
AB  - Regenerative medicine and stem cell therapy may represent the solution for the
      treatment of non-curable human diseases such as type 1 diabetes. In this context
      of growing demand for functional and safe stem cells, human amniotic epithelial
      cells (hAECs) from term placenta have attracted increasing interest for their
      wide availability, stem cell properties, and differentiation plasticity, which
      make them a promising tool for stem cell-based therapeutic applications. We
      initially assayed the stemness characteristics of hAECs in serum-free conditions.
      Subsequently we developed a culture procedure on extracellular matrix for the
      formation of three-dimensional (3D) spheroids. Finally, we tested the
      immunomodulation and differentiation potential of hAEC spheroids: the presence of
      pancreatic endocrine hormones was revealed with transmission electron microscopy
      and immunofluorescence analyses; the release of C-peptide in hyperglycemic
      conditions was assayed with ELISA. The serum-free culture conditions we applied
      proved to maintain the basic stemness characteristics of hAECs. We also
      demonstrated that 3D spheroids formed by hAECs in extracellular matrix can be
      induced to differentiate into insulin-producing cells. Finally, we proved that
      control and induced cells equally inhibit the proliferation of activated
      mononuclear cells. The results of this study highlight the properties of amnion
      derived epithelial cells as promising and abundant source for cell-based
      therapies. In particular we are the first group to show the in vitro pancreatic
      induction of hAECs cultured on extracellular matrix in a 3D fashion. We
      accordingly propose the outcomes of this study as a novel contribution to the
      development of future cell replacement therapies involving placenta-derived
      cells. 

PMID- 26216909
TI  - Evaluation of resistance to low pH and bile salts of human Lactobacillus spp.
      isolates.
AB  - There are nearly 100 trillion bacteria in the intestine that together form the
      intestinal microbiota. They are 'good' bacteria because they help to maintain a
      physiological balance and are called probiotics. Probiotics must have some
      important characteristics: be safe for humans, be resistant to the low pH in the
      stomach, as well as bile salts and pancreatic juice. Indeed, their survival is
      the most important factor, so that they can arrive alive in the intestine and are
      able to form colonies, at least temporarily. The aim of our study was the
      evaluation of resistance of Lactobacillus isolates from fecal and oral swabs
      compared to that found in a commercial product. Seven strains were randomly
      chosen: L. jensenii, L. gasseri, L. salivarius, L. fermentum, L. rhamnosus, L.
      crispatus, and L. delbrueckii. We observed a large variability in the results: L.
      gasseri and L. fermentum were the most resistance to low pH, while only L.
      gasseri showed the best survival rate to bile salts. Interestingly, the
      commercial product did not show tolerance to both low pH and bile salts. 

PMID- 26216910
TI  - Human lymphocytic B-leukemia cell line treatment with the bacterial toxin
      listeriolysin O and rituximab (anti-CD20 antibody): Effects of similar
      localization of their receptors.
AB  - Small B-cell lymphocytic lymphoma/chronic lymphocytic leukemia, which typically
      affects elderly people, is a group of conditions that are not clinically uniform.
      It has been suggested that using the combined activity of the monoclonal antibody
      anti-CD20 (rituximab) and Listeria monocytogenes toxin listeriolysin O (LLO) for
      this condition could produce an enhanced treatment effect. Here, we tested the
      effect of the joint activity of rituximab and LLO, which is a cell membrane
      toxin, in human leukemia cell lines. The human B-leukemia Raji cell line, which
      expresses CD20, and the T-cell Jurkat cell line, which does not express CD20, for
      comparison were used in model tests. Cell cytotoxicity of rituximab or LLO and
      both applied jointly to the cell lines was compared in the presence of human
      plasma complement. Optimal cytotoxic effects dependent on rituximab or LLO
      concentration were tested separately. LD50 values were determined and used for
      optimal application of a mixture of the two factors. The cytotoxic effect on Raji
      cells of both rituximab and LLO was more than 2.5 times that of LLO alone and 1.5
      times that of rituximab alone. At the highest tested concentrations, a mixture of
      the tested factors had a non-specific cytotoxic effect on the Jurkat cell line,
      as well. The rituximab and LLO binding sites appear to be in a similar region of
      the Raji leukemia cell membrane, suggesting an effective interaction of both
      factors. The joint interaction of these compounds in cell membrane pore formation
      suggests an explanation for the more effective cytotoxic activity that their
      combination was observed in this experiment. 

PMID- 26216917
TI  - What Is the Clinical Utility of the Ankle-Brachial Index in Patients With
      Diabetic Foot Ulcers and Radiographic Arterial Calcification?
AB  - The purpose of this study was to analyze the influence of radiographic arterial
      calcification (RAC) on the clinical interpretation of ankle-brachial index (ABI)
      values in patients with diabetic foot ulcers. We analyzed a retrospective
      clinical database of 60 patients with diabetic foot ulcers from the Diabetic Foot
      Unit (Complutense University, Madrid, Spain) between January 2012 and March 2014.
      For each patient, anteroposterior XR-plains were evaluated, and the ABI and toe
      brachial index (TBI) were assessed by an experienced clinician. To analyze the
      correlation among quantitative variables, we applied the Pearson correlation
      coefficient. Fifty percent (n = 9/18) of our patients with a normal ABI and RAC
      had a TBI < 0.7 associated with peripheral arterial disease (PAD). In patients
      with RAC, the prevalence of a normal ABI (72%, 18/25) was higher than in patients
      without RAC (52%, 11/21). The Pearson correlation coefficient among the ABI and
      TBI in patients with an ABI < 1.4 (n = 46) was lesser (r = .484, P = .001) than
      in patients with an ABI < 1.4 but without RAC (n = 21; r = .686, P = .001). ABI
      values between 0.9 and 1.4 would be falsely considered as normal and could
      underestimate the prevalence of PAD, especially in patients with neuropathy,
      diabetic foot ulcers, or RAC. 

PMID- 26216918
TI  - Social Structure, Anomie, and National Levels of Homicide.
AB  - Merton's "Social Structure and Anomie" seeks to explain how "socio-cultural"
      influences exert "definite pressures" to engage in non-conformity. Despite having
      a significant influence, few studies have assessed the degree to which Merton's
      propositions explain cross-national variation in levels of crime. Using data on
      national levels of homicide, data from the World Values Survey, and other
      structural controls, the present study assesses the degree to which
      deinstitutionalization, demoralization, and blocked opportunity interact to
      explain crime cross-nationally. Results provide a high degree of support for
      Merton's assertion that societal types characterized by relatively high levels of
      materialism and/or demoralization or deinstitutionalization suffer from higher
      levels of homicide. However, there is less support for Merton's assertion that
      inequality interacts with various societal patterns of means/ends integration in
      a meaningful way. Findings and implications for the utility of classical anomie
      as a general macro-level theory are discussed. 

PMID- 26216919
TI  - Choice and Hope.
AB  - Hope theory identifies goal, pathway, and agency as essential elements of hope
      that promote and maximize the effectiveness of treatment. Much significant
      evidence has indicated that hope is a strong predictor of substance involvement
      recovery. This study aimed to test the effectiveness of choice-based reality
      therapy in strengthening hope in recovery for women convicted of drug offences in
      Taiwan. The participants in the substance involvement treatment program were 44
      incarcerated women convicted of drug offences, who were randomly selected and
      randomly assigned to equal-sized experimental and control groups. The results of
      the study, obtained by ANCOVA analysis, showed significant differences between
      the two groups in the posttest scores for sense of hope as measured in the
      subscales of goal setting and pursuing, adequate energy, and controlling pathway.
      The effect size values of the three variables suggested a moderate practical
      significance. The evidence provided in the present study indicates that, upon
      completion of the choice-based reality therapy for substance involvement, when
      compared with those who had not yet attended the program, Taiwanese women
      convicted of drug offences reported a significantly higher level of hope. Hope
      was measured by their ability in setting goals and overcoming obstacles and
      persistence in pursuing the goals they had set up, energy for recovery, and their
      capacity to set up pathways based on their goals. The findings highlight the
      value of choice-based reality therapy in enhancing hope of recovery for women
      convicted of drug offences.

PMID- 26216921
TI  - A rare case of vulval pilonidal sinus: incidental diagnosis.
AB  - A 63-year-old woman presented with a 4-week history of vulval bleeding. On
      examination, an 8 mm fleshy irregular vascular lesion was present on the vulva in
      the periclitoreal area. This vulval lesion was treated by surgical excision.
      Histological analysis showed irregular pieces of skin partly covered by
      hyperplastic squamous epithelium. There were areas of fistulous-like endophytic
      proliferations lined by hyperplastic squamous epithelial cells. The intervening
      stroma showed granulation tissue with severe active chronic inflammation. At
      least five hair follicle shafts surrounded by foreign body type giant cells were
      also identified within the inflamed area. There was no evidence of dysplasia or
      malignancy. This chronically inflamed fistulous tract together with hair shafts
      within the wall of the tract were diagnostic of a pilonidal sinus of the vulva.
      This case report summarises the importance of diagnosing pilonidal sinus at an
      unusual location.

PMID- 26216920
TI  - Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an
      international task force consensus statement.

PMID- 26216922
TI  - Fetal anaemia from red blood cell membrane defect and co-inherited haemoglobin
      Constant Spring.
AB  - The case presented here is an example of hereditary red blood cell membrane
      defect with a co-inherited haemoglobin Constant Spring. This case is of an
      anaemic fetus that presented with isolated ascites at 18 weeks of gestation.
      Fetal blood analysis revealed abnormal shaped red blood cells. The same pattern
      of red blood cell morphology was also seen on paternal peripheral blood smear.
      Intrauterine blood transfusions were given twice to correct fetal anaemia. The
      fetus showed a good response to the transfusions and was delivered at term with
      mild anaemia and did not need blood transfusion after birth. This report
      describes a natural course of red blood cell membrane defect with co-inherited
      haemoglobin Constant Spring, indicating that the course of disease was more
      severe during fetal life. Intrauterine transfusion supported the transition of
      the fetus through the critical period in utero to a healthier life after birth.

PMID- 26216923
TI  - Iliacus haematoma causing femoral nerve palsy: an unusual trampolining injury.
AB  - We report the case of a 15-year-old boy who presented to accident and emergency
      following a trampolining injury. Initially, the patient was discharged, diagnosed
      with a soft tissue injury, but he re-presented 48 h later with worsening low back
      pain and neurological symptoms in the left leg. Subsequent MRI revealed a left
      iliacus haematoma causing a femoral nerve palsy. The patient was managed
      conservatively and by 6 months post injury all symptoms had resolved. This is the
      first reported case of an iliacus haematoma causing a femoral nerve palsy, after
      a trampolining injury. We believe this case highlights to our fellow clinicians
      the importance of a detailed history when assessing patients with trampolining
      injuries to evaluate the true force of injury. It also acts as a reference for
      clinicians in managing similar cases in future.

PMID- 26216924
TI  - Mixed epithelial and stromal tumour of the kidney.
AB  - Mixed epithelial and stromal tumour (MESTK) of the kidney is a rare and benign
      tumour composed of epithelial and spindle cell stromal components with solid and
      cystic architecture. MESTK is most commonly seen in perimenopausal women,
      especially those on long-term oestrogen therapy. MESTK is often asymptomatic,
      detected incidentally on imaging studies. Diagnosis is established by
      histological examination. Microscopy is reminiscent of ovarian stroma. Malignant
      transformation, metastasis and recurrences are extremely rare. Treatment is
      surgical excision of the tumour with usually no recurrences after surgery and
      good prognosis. We describe a case of MESTK found incidentally on imaging
      studies. 

PMID- 26216925
TI  - Plexiform angiomyxoid myofibroblastic tumour of the duodenum: a rare entity.
AB  - Plexiform angiomyxoid myofibroblastic tumour (PAMT) has recently emerged as a new
      entity among gastrointestinal mesenchymal tumours. All of the 27 cases reported
      until now originated from the stomach. We report the first case of a duodenal
      PAMT arising from the first part of the duodenum in a 19-year-old woman
      presenting with upper abdominal pain and an abdominal lump. 

PMID- 26216926
TI  - Correction.

PMID- 26216927
TI  - Frontal sinus mucocoele: a rare cause of ptosis.
AB  - A 73-year-old man, with no medical history of note, presented with a 4-week
      history of an isolated left-sided ptosis and associated periorbital and retro
      orbital discomfort. His pupils were spared, his eye movements were not restricted
      and he was not proptosed. A prompt CT orbits and head scan revealed a large left
      frontal sinus mucocoele that had eroded into the left orbit. The patient had
      successful endoscopic sinus surgery under the ear, nose and throat team and 1
      month later was seen in ophthalmology clinic. His ptosis and discomfort had fully
      resolved and he had no neurological sequelae from the surgery.

PMID- 26216928
TI  - Correction.

PMID- 26216929
TI  - A rare cause of genital ulcer.

PMID- 26216930
TI  - Cutaneous coccidioidomycosis: a great mimicker.

PMID- 26216932
TI  - Editorial.

PMID- 26216931
TI  - Impact of immature platelets on platelet response to ticagrelor and prasugrel in
      patients with acute coronary syndrome.
AB  - AIMS: The influence of reticulated platelets (RPs) on platelet inhibition by
      ticagrelor when compared with prasugrel is unknown. We aimed to determine the
      influence of RPs on adenosine diphosphate- (ADP-) induced platelet aggregation in
      patients with acute coronary syndrome who were randomly assigned to receive
      either ticagrelor or prasugrel for P2Y12 receptor inhibition. METHODS AND
      RESULTS: One hundred and twenty-four patients were prospectively enrolled. The
      immature platelet fraction (IPF) was measured by an automated haematoanalyzer and
      platelet aggregation was assessed by multiple electrode aggregometry. In a
      subgroup of patients (n = 28) ADP-induced P-selectin expression was measured in
      dependence of the time point of study drug intake in RPs that were discriminated
      from mature platelets by thiazole-orange (TO) staining. The primary endpoint was
      the correlation of platelet aggregation and IPF in ticagrelor- vs. prasugrel
      treated patients. Platelet aggregation significantly correlated with IPF in
      patients who received prasugrel (r = 0.41, P < 0.001). In contrast, no
      correlation between IPF and platelet aggregation was observed in ticagrelor
      treated patients (r = 0.08, P = 0.51, P for difference of correlation
      coefficients P = 0.05). Within the TO-positive RP fraction, P-selectin expression
      was significantly higher in prasugrel when compared with ticagrelor-treated
      individuals (prasugrel 18.6 +/- 16.0% vs. ticagrelor 11.5 +/- 6.0%, P = 0.047). A
      time-dependent P-selectin expression was observed in prasugrel but not in
      ticagrelor-treated patients (prasugrel early 11.9 +/- 9.4% vs. late 26.3 +/-
      19.0%, P = 0.031, ticagrelor early 9.6 +/- 4.9% vs. late 13.5 +/- 6.6%, P =
      0.127). CONCLUSION: Reticulated platelets show a greater impact on platelet
      reactivity in response to prasugrel when compared with ticagrelor.

PMID- 26216933
TI  - Morphological distribution of ovarian cancer from Cancer Incidence in Five
      Continents Vol. X.

PMID- 26216934
TI  - Intravenous immunoglobulin skews macrophages to an anti-inflammatory, IL-10
      producing activation state.
AB  - Intravenous Ig is used to treat autoimmune or autoinflammatory disorders, but the
      mechanism by which it exerts its immunosuppressive activity is not understood
      completely. To examine the impact of intravenous Ig on macrophages, we compared
      cytokine production by LPS-activated macrophages in the presence and absence of
      intravenous Ig. Intravenous Ig treatment induced robust production of IL-10 in
      response to LPS, relative to LPS stimulation alone, and reduced production of
      proinflammatory cytokines. This anti-inflammatory, intravenous Ig-induced
      activation was sustained for 24 h but could only be induced if intravenous Ig
      were provided within 1 h of LPS stimulation. Intravenous Ig activation led to
      enhanced and prolonged activation of MAPKs, Erk1/2, p38, and Erk5, and inhibition
      of each reduced intravenous Ig-induced IL-10 production and suppression of IL
      12/23p40. IL-10 production occurred rapidly in response to intravenous Ig + LPS
      and was sufficient to reduce proinflammatory IL-12/23p40 production in response
      to LPS. IL-10 induction and reduced IL-12/23p40 production were transcriptionally
      regulated. IL-10 played a direct role in reducing proinflammatory cytokine
      production by macrophages treated with intravenous Ig + LPS, as macrophages from
      mice deficient in the IL-10R beta chain or in IL-10 were compromised in their
      ability to reduce proinflammatory cytokine production. Finally, intraperitoneal
      injection of intravenous Ig or intravenous Ig + LPS into mice activated
      macrophages to produce high levels of IL-10 during subsequent or concurrent LPS
      challenge, respectively. These findings identify IL-10 as a key anti-inflammatory
      mediator produced by intravenous Ig-treated macrophages and provide insight into
      a novel mechanism by which intravenous Ig may dampen down inflammatory responses
      in patients with autoimmune or autoinflammatory diseases. 

PMID- 26216935
TI  - Hepatic CD206-positive macrophages express amphiregulin to promote the
      immunosuppressive activity of regulatory T cells in HBV infection.
AB  - Hepatitis B virus is a major cause of chronic liver inflammation worldwide.
      Innate and adaptive immune responses work together to restrain or eliminate
      hepatitis B virus in the liver. Compromised or failed adaptive immune response
      results in persistent virus replication and spread. How to promote antiviral
      immunity is a research focus for hepatitis B virus prevention and therapy. In
      this study, we investigated the role of macrophages in the regulation of
      antiviral immunity. We found that F4/80(+)CD206(+)CD80(lo/+) macrophages were a
      particular hepatic macrophage subset that expressed amphiregulin in our mouse
      hepatitis B virus infection model. CD206(+) macrophage-derived amphiregulin
      promoted the immunosuppressive activity of intrahepatic regulatory T cells,
      demonstrated by higher expression of CTLA-4, ICOS, and CD39, as well as stronger
      inhibition of antiviral function of CD8(+) T cells. Amphiregulin-neutralizing
      antibody diminished the effect of CD206(+) macrophages on regulatory T cells. In
      addition, we found that CD206(+) macrophage-derived amphiregulin activated
      mammalian target of rapamycin signaling in regulatory T cells, and this mammalian
      target of rapamycin activation was essential for promotion of regulatory T cell
      activity by CD206(+) macrophages. Adoptive transfer of CD206(+) macrophages into
      hepatitis B virus-infected mice increased cytoplasmic hepatitis B virus DNA in
      hepatocytes and also increased serum hepatitis B surface antigen. The antiviral
      activity of CD8(+) T cells was decreased after macrophage transfer. Therefore,
      our research indicated that amphiregulin produced by CD206(+) macrophages plays
      an important role in modulating regulatory T cell function and subsequently
      restrains the antiviral activity of CD8(+) T cells. Our study offers new insights
      into the immunomodulation in hepatitis B virus infection. 

PMID- 26216936
TI  - Phospholipid scramblase 1 is required for beta2-glycoprotein I binding in hypoxia
      and reoxygenation-induced endothelial inflammation.
AB  - Multiple pathologic conditions, including hemorrhage, tumor angiogenesis, and
      ischemia-reperfusion events, will result in hypoxia and subsequent reperfusion.
      Previous studies have analyzed the lipid changes within whole tissues and
      indicated that ischemia-reperfusion altered tissue and cellular phospholipids.
      Using an in vitro cell culture model of hypoxia and reoxygenation, we examined
      the endothelial lipid changes. We hypothesized that phospholipid scramblase 1, a
      protein that regulates bilayer asymmetry, is involved in altering the
      phospholipids of endothelial cells during hypoxia, a component of ischemia,
      leading to beta2-glycoprotein I and IgM binding and subsequent lipid-mediated,
      inflammatory responses. We have completed the first comprehensive study of steady
      state phospholipid scramblase 1 mRNA levels, protein expression, and activity
      under conditions of hypoxia and reoxygenation. Phospholipid scramblase 1
      regulates phosphatidylserine exposure in response to oxygen stress, leading to
      beta2-glycoprotein I and IgM binding and lipid-mediated, inflammatory responses. 

PMID- 26216937
TI  - Neutrophils rapidly transit inflamed lymphatic vessel endothelium via integrin
      dependent proteolysis and lipoxin-induced junctional retraction.
AB  - Neutrophils are the first leukocyte population to be recruited from the
      circulation following tissue injury or infection, where they play key roles in
      host defense. However, recent evidence indicates recruited neutrophils can also
      enter lymph and shape adaptive immune responses downstream in draining lymph
      nodes. At present, the cellular mechanisms regulating neutrophil entry to
      lymphatic vessels and migration to lymph nodes are largely unknown. Here, we have
      investigated these events in an in vivo mouse Mycobacterium bovis bacillus
      Calmette-Guerin vaccination model, ex vivo mouse dermal explants, and in vitro
      Transwell system comprising monolayers of primary human dermal lymphatic
      endothelial cells. We demonstrate that neutrophils are reliant on endothelial
      activation for adhesion, initially via E-selectin and subsequently, by integrin
      mediated binding to ICAM-1 and VCAM-1, combined with CXCL8-dependent chemotaxis.
      Moreover, we reveal that integrin-mediated neutrophil adhesion plays a pivotal
      role in subsequent transmigration by focusing the action of matrix
      metalloproteinases and the 15-lipoxygenase-1-derived chemorepellent 12(S)
      hydroxyeicosatetraenoic acid at neutrophil:endothelial contact sites to induce
      transient endothelial junctional retraction and rapid, selective neutrophil
      trafficking. These findings reveal an unexpectedly intimate collaboration between
      neutrophils and the lymphatic vessel endothelium, in which these phagocytic
      leukocytes act as pathfinders for their own transit during inflammation. 

PMID- 26216938
TI  - Recent findings on the role of natural killer cells in the pathogenesis of
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is a chronic, multifactorial autoimmune disease of
      complex etiology, characterized by loss of tolerance to nuclear autoantigens,
      expansion of autoreactive T and B cell clones, polyclonal B cell activation that
      gives rise to hypergammaglobulinemia, and increased autoantibody production, as
      well as immune complex deposition and multiorgan tissue inflammation. As disease
      progresses, immune cells, mainly T cells and macrophages, infiltrate affected
      organs and amplify the local inflammatory response. Natural killer cells are
      large, granular lymphocytes that are an important link between the innate and
      adaptive immune systems; variations in their activity correlate with several
      autoimmune diseases. To date, the literature has disregarded natural killer cells
      as relevant modulators in systemic lupus erythematosus pathogenesis, as these
      cells are few in number and show a dysfunctional phenotype in patients with
      active systemic lupus erythematosus. This review focuses on research that could
      help define the role of natural killer cells in systemic lupus erythematosus and
      their function in regulating this autoimmune disorder in nonlymphoid organs. 

PMID- 26216939
TI  - Rapid externalization of 27-kDa heat shock protein (HSP27) and atypical cell
      death in neutrophils treated with the sphingolipid analog drug FTY720.
AB  - The sphingolipid analog fingolimod is known to induce apoptosis of tumor cells
      and lymphocytes. Its effect on neutrophils has not been investigated so far.
      Here, we describe a fingolimod-induced atypical cell death mechanism in human
      neutrophils, characterized by rapid translocation of heat shock protein 27 to the
      cell surface, extensive cell swelling and vacuolization, atypical chromatin
      staining and nuclear morphology, and phosphorylation of mixed lineage kinase
      domain-like protein. Fingolimod also induces typical apoptotic features,
      including rapid externalization of phosphatidylserine and activation of caspase
      8. Fingolimod-induced neutrophil death is independent of sphingosine-1-phosphate
      receptors and positively regulated by protein phosphatase A. Externalization of
      phosphatidylserine and heat shock protein 27 can be partially inhibited by
      inhibitors of caspase-8 [Z-Ile-Glu(O-Me)-Thr-Asp(O-Me)-fluoromethyl ketone],
      receptor-interacting protein kinase 1 (necrostatin-1), receptor-interacting
      protein kinase 3 (necrosulfonamide), and heat shock protein 90 [geldanamycin and
      17-(dimethylaminoethylamino)-17-demethoxygeldanamycin]. Furthermore, NADPH
      oxidase 1 inhibition with diphenyleneiodonium chloride protects neutrophils
      against fingolimod-mediated cell death. Overall, these observations suggest that
      fingolimod acts through a mechanism involving the necrosome signaling complex and
      the oxidative stress machinery. 

PMID- 26216940
TI  - The behavioural variant frontotemporal dementia (bvFTD) syndrome in psychiatry.
AB  - The primary goal of this article is to critically discuss the syndromic overlap
      that exists between early behavioural variant frontotemporal dementia (bvFTD)-
      the most common clinical syndrome associated with frontotemporal lobar
      degeneration (FTLD)--and several primary psychiatric disorders. We begin by
      summarising the current state of knowledge regarding FTLD, including the recent
      discovery of FTLD-causative genetic mutations. Clinicopathological correlations
      in FTLD are subsequently discussed, while emphasising that clinical syndromes of
      FTD are dictated by the distribution of FTLD pathology in the brain. We then
      review a large number of cases with suspected and confirmed bvFTD that had
      previously been diagnosed with a primary psychiatric disorder. The clinical and
      neuroscientific implications of this overlap are discussed, focusing on the
      importance of early diagnosis for clinical and therapeutic reasons. We propose
      that largely due to the paucity of biomarkers for primary psychiatric disorders,
      and the limited use of FTLD-related biomarkers by psychiatrists at present, it is
      very difficult to separate patients with early bvFTD from those with primary
      psychiatric disorders based on clinical grounds. Furthermore, specific
      limitations of the Diagnostic and Statistical Manual of Mental Disorders (DSM) 5
      criteria for bvFTD may inadvertently discourage recognition of bvFTD in mental
      health settings. Clinically, more research is needed to develop tools that allow
      early differentiation of bvFTD from primary psychiatric disease, as bvFTD
      therapies will likely be most effective in the earliest stages of disease. From a
      neuroscience perspective, we argue that bvFTD provides an excellent paradigm for
      investigating the neural basis of psychiatric disorders.

PMID- 26216941
TI  - EEG-fMRI in the presurgical evaluation of temporal lobe epilepsy.
AB  - OBJECTIVE: Drug-resistant temporal lobe epilepsy (TLE) often requires thorough
      investigation to define the epileptogenic zone for surgical treatment. We used
      simultaneous interictal scalp EEG-fMRI to evaluate its value for predicting long
      term postsurgical outcome. METHODS: 30 patients undergoing presurgical evaluation
      and proceeding to temporal lobe (TL) resection were studied. Interictal
      epileptiform discharges (IEDs) were identified on intra-MRI EEG and used to build
      a model of haemodynamic changes. In addition, topographic electroencephalographic
      correlation maps were calculated between the average IED during video-EEG and
      intra-MRI EEG, and used as a condition. This allowed the analysis of all data
      irrespective of the presence of IED on intra-MRI EEG. Mean follow-up after
      surgery was 46 months. International League Against Epilepsy (ILAE) outcomes 1
      and 2 were considered good, and 3-6 poor, surgical outcome. Haemodynamic maps
      were classified according to the presence (Concordant) or absence (Discordant) of
      Blood Oxygen Level-Dependent (BOLD) change in the TL overlapping with the
      surgical resection. RESULTS: The proportion of patients with good surgical
      outcome was significantly higher (13/16; 81%) in the Concordant than in the
      Discordant group (3/14; 21%) (chi(2) test, Yates correction, p=0.003) and
      multivariate analysis showed that Concordant BOLD maps were independently related
      to good surgical outcome (p=0.007). Sensitivity and specificity of EEG-fMRI
      results to identify patients with good surgical outcome were 81% and 79%,
      respectively, and positive and negative predictive values were 81% and 79%,
      respectively. INTERPRETATION: The presence of significant BOLD changes in the
      area of resection on interictal EEG-fMRI in patients with TLE retrospectively
      confirmed the epileptogenic zone. Surgical resection including regions of
      haemodynamic changes in the TL may lead to better postoperative outcome.

PMID- 26216942
TI  - MRP4 Modulation of the Guanylate Cyclase-C/cGMP Pathway: Effects on Linaclotide
      Induced Electrolyte Secretion and cGMP Efflux.
AB  - MRP4 mediates the efflux of cGMP and cAMP and acts as an important regulator of
      these secondary messengers, thereby affecting signaling events mediated by cGMP
      and cAMP. Immunofluorescence staining showed high MRP4 expression localized
      predominantly in the apical membrane of rat colonic epithelium. In vitro studies
      were performed using a rat colonic mucosal layer mounted in an Ussing chamber.
      Linaclotide activation of the guanylate cyclase-C (GC-C)/cGMP pathway induced a
      concentration-dependent increase in transepithelial ion current [short-circuit
      current (Isc)] across rat colonic mucosa (EC50: 9.2 nM). Pretreatment of colonic
      mucosa with the specific MRP4 inhibitor MK571 potentiated linaclotide-induced
      electrolyte secretion and augmented linaclotide-stimulated intracellular cGMP
      accumulation. Notably, pretreatment with the phosphodiesterase 5 inhibitor
      sildenafil increased basal Isc, but had no amplifying effect on linaclotide
      induced Isc. MRP4 inhibition selectively affected the activation phase, but not
      the deactivation phase, of linaclotide. In contrast, incubation with a GC-C/Fc
      chimera binding to linaclotide abrogated linaclotide-induced Isc, returning to
      baseline. Furthermore, linaclotide activation of GC-C induced cGMP secretion from
      the apical and basolateral membranes of colonic epithelium. MRP4 inhibition
      blocked cGMP efflux from the apical membrane, but not the basolateral membrane.
      These data reveal a novel, previously unrecognized mechanism that functionally
      couples GC-C-induced luminal electrolyte transport and cGMP secretion to
      spatially restricted, compartmentalized regulation by MRP4 at the apical membrane
      of intestinal epithelium. These findings have important implications for
      gastrointestinal disorders with symptoms associated with dysregulated fluid
      homeostasis, such as irritable bowel syndrome with constipation, chronic
      idiopathic constipation, and secretory diarrhea. 

PMID- 26216944
TI  - Energy flow and the "grassification" of desert shrublands.

PMID- 26216943
TI  - AAV9 delivering a modified human Mullerian inhibiting substance as a gene therapy
      in patient-derived xenografts of ovarian cancer.
AB  - To improve ovarian cancer patient survival, effective treatments addressing
      chemoresistant recurrences are particularly needed. Mullerian inhibiting
      substance (MIS) has been shown to inhibit the growth of a stem-like population of
      ovarian cancer cells. We have recently engineered peptide modifications to human
      MIS [albumin leader Q425R MIS (LRMIS)] that increase production and potency in
      vitro and in vivo. To test this novel therapeutic peptide, serous malignant
      ascites from highly resistant recurrent ovarian cancer patients were isolated and
      amplified to create low-passage primary cell lines. Purified recombinant LRMIS
      protein successfully inhibited the growth of cancer spheroids in vitro in a panel
      of primary cell lines in four of six patients tested. Adeno-associated virus
      (AAV) -delivered gene therapy has undergone a clinical resurgence with a good
      safety profile and sustained gene expression. Therefore, AAV9 was used as a
      single i.p. injection to deliver LRMIS to test its efficacy in inhibiting growth
      of palpable tumors in patient-derived ovarian cancer xenografts from ascites
      (PDXa). AAV9-LRMIS monotherapy resulted in elevated and sustained blood
      concentrations of MIS, which significantly inhibited the growth of three of five
      lethal chemoresistant serous adenocarcinoma PDXa models without signs of
      measurable or overt toxicity. Finally, we tested the frequency of MIS type II
      receptor expression in a tissue microarray of serous ovarian tumors by
      immunohistochemistry and found that 88% of patients bear tumors that express the
      receptor. Taken together, these preclinical data suggest that AAV9-LRMIS provides
      a potentially well-tolerated and effective treatment strategy poised for testing
      in patients with chemoresistant serous ovarian cancer. 

PMID- 26216945
TI  - MIR retrotransposon sequences provide insulators to the human genome.
AB  - Insulators are regulatory elements that help to organize eukaryotic chromatin via
      enhancer-blocking and chromatin barrier activity. Although there are several
      examples of transposable element (TE)-derived insulators, the contribution of TEs
      to human insulators has not been systematically explored. Mammalian-wide
      interspersed repeats (MIRs) are a conserved family of TEs that have substantial
      regulatory capacity and share sequence characteristics with tRNA-related
      insulators. We sought to evaluate whether MIRs can serve as insulators in the
      human genome. We applied a bioinformatic screen using genome sequence and
      functional genomic data from CD4(+) T cells to identify a set of 1,178 predicted
      MIR insulators genome-wide. These predicted MIR insulators were computationally
      tested to serve as chromatin barriers and regulators of gene expression in CD4(+)
      T cells. The activity of predicted MIR insulators was experimentally validated
      using in vitro and in vivo enhancer-blocking assays. MIR insulators are enriched
      around genes of the T-cell receptor pathway and reside at T-cell-specific
      boundaries of repressive and active chromatin. A total of 58% of the MIR
      insulators predicted here show evidence of T-cell-specific chromatin barrier and
      gene regulatory activity. MIR insulators appear to be CCCTC-binding factor (CTCF)
      independent and show a distinct local chromatin environment with marked peaks for
      RNA Pol III and a number of histone modifications, suggesting that MIR insulators
      recruit transcriptional complexes and chromatin modifying enzymes in situ to help
      establish chromatin and regulatory domains in the human genome. The provisioning
      of insulators by MIRs across the human genome suggests a specific mechanism by
      which TE sequences can be used to modulate gene regulatory networks. 

PMID- 26216946
TI  - Relation between stability and resilience determines the performance of early
      warning signals under different environmental drivers.
AB  - Shifting patterns of temporal fluctuations have been found to signal critical
      transitions in a variety of systems, from ecological communities to human
      physiology. However, failure of these early warning signals in some systems calls
      for a better understanding of their limitations. In particular, little is known
      about the generality of early warning signals in different deteriorating
      environments. In this study, we characterized how multiple environmental drivers
      influence the dynamics of laboratory yeast populations, which was previously
      shown to display alternative stable states [Dai et al., Science, 2012]. We
      observed that both the coefficient of variation and autocorrelation increased
      before population collapse in two slowly deteriorating environments, one with a
      rising death rate and the other one with decreasing nutrient availability. We
      compared the performance of early warning signals across multiple environments as
      "indicators for loss of resilience." We find that the varying performance is
      determined by how a system responds to changes in a specific driver, which can be
      captured by a relation between stability (recovery rate) and resilience (size of
      the basin of attraction). Furthermore, we demonstrate that the positive
      correlation between stability and resilience, as the essential assumption of
      indicators based on critical slowing down, can break down in this system when
      multiple environmental drivers are changed simultaneously. Our results suggest
      that the stability-resilience relation needs to be better understood for the
      application of early warning signals in different scenarios.

PMID- 26216947
TI  - Decadal acidification in the water masses of the Atlantic Ocean.
AB  - Global ocean acidification is caused primarily by the ocean's uptake of CO2 as a
      consequence of increasing atmospheric CO2 levels. We present observations of the
      oceanic decrease in pH at the basin scale (50  degrees S-36  degrees N) for the
      Atlantic Ocean over two decades (1993-2013). Changes in pH associated with the
      uptake of anthropogenic CO2 (DeltapHCant) and with variations caused by
      biological activity and ocean circulation (DeltapHNat) are evaluated for
      different water masses. Output from an Institut Pierre Simon Laplace climate
      model is used to place the results into a longer-term perspective and to
      elucidate the mechanisms responsible for pH change. The largest decreases in pH
      (?pH) were observed in central, mode, and intermediate waters, with a maximum
      DeltapH value in South Atlantic Central Waters of -0.042 +/- 0.003. The DeltapH
      trended toward zero in deep and bottom waters. Observations and model results
      show that pH changes generally are dominated by the anthropogenic component,
      which accounts for rates between -0.0015 and -0.0020/y in the central waters. The
      anthropogenic and natural components are of the same order of magnitude and
      reinforce one another in mode and intermediate waters over the time period. Large
      negative DeltapHNat values observed in mode and intermediate waters are driven
      primarily by changes in CO2 content and are consistent with (i) a poleward shift
      of the formation region during the positive phase of the Southern Annular Mode in
      the South Atlantic and (ii) an increase in the rate of the water mass formation
      in the North Atlantic.

PMID- 26216948
TI  - Generation of knock-in primary human T cells using Cas9 ribonucleoproteins.
AB  - T-cell genome engineering holds great promise for cell-based therapies for
      cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic
      manipulation of human T cells has been challenging. Improved tools are needed to
      efficiently "knock out" genes and "knock in" targeted genome modifications to
      modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9
      technology is facilitating genome engineering in many cell types, but in human T
      cells its efficiency has been limited and it has not yet proven useful for
      targeted nucleotide replacements. Here we report efficient genome engineering in
      human CD4(+) T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs).
      Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP
      electroporation caused up to ~40% of cells to lose high-level cell-surface
      expression of CXCR4, and edited cells could be enriched by sorting based on low
      CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair
      template oligonucleotides generated a high frequency of targeted genome
      modifications in primary T cells. Targeted nucleotide replacement was achieved in
      CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated
      target for tumor immunotherapy. Deep sequencing of a target site confirmed that
      Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency,
      which accounted for up to approximately one-third of total editing events. These
      results establish Cas9 RNP technology for diverse experimental and therapeutic
      genome engineering applications in primary human T cells. 

PMID- 26216949
TI  - The isolation of an RNA aptamer targeting to p53 protein with single amino acid
      mutation.
AB  - p53, known as a tumor suppressor, is a DNA binding protein that regulates cell
      cycle, activates DNA repair proteins, and triggers apoptosis in multicellular
      animals. More than 50% of human cancers contain a mutation or deletion of the p53
      gene, and p53R175 is one of the hot spots of p53 mutation. Nucleic acid aptamers
      are short single-stranded oligonucleotides that are able to bind various targets,
      and they are typically isolated from an experimental procedure called systematic
      evolution of ligand exponential enrichment (SELEX). Using a previously
      unidentified strategy of contrast screening with SELEX, we have isolated an RNA
      aptamer targeting p53R175H. This RNA aptamer (p53R175H-APT) has a significantly
      stronger affinity to p53R175H than to the wild-type p53 in both in vitro and in
      vivo assays. p53R175H-APT decreased the growth rate, weakened the migration
      capability, and triggered apoptosis in human lung cancer cells harboring
      p53R175H. Further analysis actually indicated that p53R175H-APT might partially
      rescue or correct the p53R175H to function more like the wild-type p53. In situ
      injections of p53R175H-APT to the tumor xenografts confirmed the effects of this
      RNA aptamer on p53R175H mutation in mice. 

PMID- 26216950
TI  - Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung
      squamous cell carcinoma patients with EGFR mutations.
AB  - The empirical criteria for defining a clinical subtype of lung cancer are
      gradually transiting from histopathology to genetic variations in driver genes.
      Targeting these driver mutations, such as sensitizing epidermal growth factor
      receptor (EGFR) mutations, has dramatically improved the prognosis of advanced
      non-small cell lung cancer (NSCLC). However, the clinical benefit of molecularly
      targeted therapy on NSCLC appears to be different between lung adenocarcinomas
      and squamous cell carcinomas (SqCCs). We report here that the resistance of lung
      SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was
      due to the activation of BMP-BMPR-Smad1/5-p70S6K. The combined treatment of these
      tumor cells with EGFR-TKI, together with inhibitors specific to BMPR or
      downstream mTOR, effectively reversed the resistance to EGFR-TKI. Moreover,
      blocking the whole PI3K-AKT-mTOR pathway with the PI3K/mTOR dual inhibitor BEZ235
      also showed efficacy in treating this subtype of lung SqCC. This study details
      the empirical basis for a feasible clinical solution for squamous cell carcinomas
      with EGFR mutations. 

PMID- 26216951
TI  - Profile of Dinshaw J. Patel.

PMID- 26216952
TI  - Systematic review of current efforts to quantify the impacts of climate change on
      undernutrition.
AB  - Malnutrition is a challenge to the health and productivity of populations and is
      viewed as one of the five largest adverse health impacts of climate change.
      Nonetheless, systematic evidence quantifying these impacts is currently limited.
      Our aim was to assess the scientific evidence base for the impact of climate
      change on childhood undernutrition (particularly stunting) in subsistence farmers
      in low- and middle-income countries. A systematic review was conducted to
      identify peer-reviewed and gray full-text documents in English with no limits for
      year of publication or study design. Fifteen manuscripts were reviewed. Few
      studies use primary data to investigate the proportion of stunting that can be
      attributed to climate/weather variability. Although scattered and limited,
      current evidence suggests a significant but variable link between weather
      variables, e.g., rainfall, extreme weather events (floods/droughts), seasonality,
      and temperature, and childhood stunting at the household level (12 of 15 studies,
      80%). In addition, we note that agricultural, socioeconomic, and demographic
      factors at the household and individual levels also play substantial roles in
      mediating the nutritional impacts. Comparable interdisciplinary studies based on
      primary data at a household level are urgently required to guide effective
      adaptation, particularly for rural subsistence farmers. Systemization of data
      collection at the global level is indispensable and urgent. We need to assimilate
      data from long-term, high-quality agricultural, environmental, socioeconomic,
      health, and demographic surveillance systems and develop robust statistical
      methods to establish and validate causal links, quantify impacts, and make
      reliable predictions that can guide evidence-based health interventions in the
      future. 

PMID- 26216953
TI  - Activity-dependent BDNF release via endocytic pathways is regulated by
      synaptotagmin-6 and complexin.
AB  - Brain-derived neurotrophic factor (BDNF) is known to modulate synapse development
      and plasticity, but the source of synaptic BDNF and molecular mechanisms
      regulating BDNF release remain unclear. Using exogenous BDNF tagged with quantum
      dots (BDNF-QDs), we found that endocytosed BDNF-QDs were preferentially localized
      to postsynaptic sites in the dendrite of cultured hippocampal neurons. Repetitive
      neuronal spiking induced the release of BDNF-QDs at these sites, and this process
      required activation of glutamate receptors. Down-regulating complexin 1/2
      (Cpx1/2) expression eliminated activity-induced BDNF-QD secretion, although the
      overall activity-independent secretion was elevated. Among eight synaptotagmin
      (Syt) isoforms examined, down-regulation of only Syt6 impaired activity-induced
      BDNF-QD secretion. In contrast, activity-induced release of endogenously
      synthesized BDNF did not depend on Syt6. Thus, neuronal activity could trigger
      the release of endosomal BDNF from postsynaptic dendrites in a Cpx- and Syt6
      dependent manner, and endosomes containing BDNF may serve as a source of BDNF for
      activity-dependent synaptic modulation. 

PMID- 26216954
TI  - Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by
      opening the mucus barrier in colon.
AB  - Colorectal cancer risk is associated with diets high in red meat. Heme, the
      pigment of red meat, induces cytotoxicity of colonic contents and elicits
      epithelial damage and compensatory hyperproliferation, leading to hyperplasia.
      Here we explore the possible causal role of the gut microbiota in heme-induced
      hyperproliferation. To this end, mice were fed a purified control or heme diet
      (0.5 MUmol/g heme) with or without broad-spectrum antibiotics for 14 d. Heme
      induced hyperproliferation was shown to depend on the presence of the gut
      microbiota, because hyperproliferation was completely eliminated by antibiotics,
      although heme-induced luminal cytotoxicity was sustained in these mice. Colon
      mucosa transcriptomics revealed that antibiotics block heme-induced differential
      expression of oncogenes, tumor suppressors, and cell turnover genes, implying
      that antibiotic treatment prevented the heme-dependent cytotoxic micelles to
      reach the epithelium. Our results indicate that this occurs because antibiotics
      reinforce the mucus barrier by eliminating sulfide-producing bacteria and mucin
      degrading bacteria (e.g., Akkermansia). Sulfide potently reduces disulfide bonds
      and can drive mucin denaturation and microbial access to the mucus layer. This
      reduction results in formation of trisulfides that can be detected in vitro and
      in vivo. Therefore, trisulfides can serve as a novel marker of colonic mucolysis
      and thus as a proxy for mucus barrier reduction. In feces, antibiotics
      drastically decreased trisulfides but increased mucin polymers that can be lysed
      by sulfide. We conclude that the gut microbiota is required for heme-induced
      epithelial hyperproliferation and hyperplasia because of the capacity to reduce
      mucus barrier function. 

PMID- 26216955
TI  - Identification and characterization of an injury-induced skeletal progenitor.
AB  - The postnatal skeleton undergoes growth, remodeling, and repair. We hypothesized
      that skeletal progenitor cells active during these disparate phases are
      genetically and phenotypically distinct. We identified a highly potent
      regenerative cell type that we term the fracture-induced bone, cartilage, stromal
      progenitor (f-BCSP) in the fracture callus of adult mice. The f-BCSP possesses
      significantly enhanced skeletogenic potential compared with BCSPs harvested from
      uninjured bone. It also recapitulates many gene expression patterns involved in
      perinatal skeletogenesis. Our results indicate that the skeletal progenitor
      population is functionally stratified, containing distinct subsets responsible
      for growth, regeneration, and repair. Furthermore, our findings suggest that
      injury-induced changes to the skeletal stem and progenitor microenvironments
      could activate these cells and enhance their regenerative potential. 

PMID- 26216957
TI  - Retraction for Moissiard and Voinnet, RNA silencing of host transcripts by
      cauliflower mosaic virus requires coordinated action of the four Arabidopsis
      Dicer-like proteins.

PMID- 26216956
TI  - Roles of unphosphorylated ISGF3 in HCV infection and interferon responsiveness.
AB  - Up-regulation of IFN-stimulated genes (ISGs) is sustained in hepatitis C virus
      (HCV)-infected livers. Here, we investigated the mechanism of prolonged ISG
      expression and its role in IFN responsiveness during HCV infection in relation to
      unphosphorylated IFN-stimulated gene factor 3 (U-ISGF3), recently identified as a
      tripartite transcription factor formed by high levels of IFN response factor 9
      (IRF9), STAT1, and STAT2 without tyrosine phosphorylation of the STATs. The level
      of U-ISGF3, but not tyrosine phosphorylated STAT1, is significantly elevated in
      response to IFN-lambda and IFN-beta during chronic HCV infection. U-ISGF3
      prolongs the expression of a subset of ISGs and restricts HCV chronic
      replication. However, paradoxically, high levels of U-ISGF3 also confer
      unresponsiveness to IFN-alpha therapy. As a mechanism of U-ISGF3-induced
      resistance to IFN-alpha, we found that ISG15, a U-ISGF3-induced protein, sustains
      the abundance of ubiquitin-specific protease 18 (USP18), a negative regulator of
      IFN signaling. Our data demonstrate that U-ISGF3 induced by IFN-lambdas and -beta
      drives prolonged expression of a set of ISGs, leading to chronic activation of
      innate responses and conferring a lack of response to IFN-alpha in HCV-infected
      liver. 

PMID- 26216958
TI  - MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time
      tumor delineation.
AB  - We present a proof of concept study designed to support the clinical development
      of mass spectrometry imaging (MSI) for the detection of pituitary tumors during
      surgery. We analyzed by matrix-assisted laser desorption/ionization (MALDI) MSI
      six nonpathological (NP) human pituitary glands and 45 hormone secreting and
      nonsecreting (NS) human pituitary adenomas. We show that the distribution of
      pituitary hormones such as prolactin (PRL), growth hormone (GH),
      adrenocorticotropic hormone (ACTH), and thyroid stimulating hormone (TSH) in both
      normal and tumor tissues can be assessed by using this approach. The presence of
      most of the pituitary hormones was confirmed by using MS/MS and pseudo-MS/MS
      methods, and subtyping of pituitary adenomas was performed by using principal
      component analysis (PCA) and support vector machine (SVM). Our proof of concept
      study demonstrates that MALDI MSI could be used to directly detect excessive
      hormonal production from functional pituitary adenomas and generally classify
      pituitary adenomas by using statistical and machine learning analyses. The tissue
      characterization can be completed in fewer than 30 min and could therefore be
      applied for the near-real-time detection and delineation of pituitary tumors for
      intraoperative surgical decision-making. 

PMID- 26216959
TI  - Mechanics of torque generation in the bacterial flagellar motor.
AB  - The bacterial flagellar motor (BFM) is responsible for driving bacterial
      locomotion and chemotaxis, fundamental processes in pathogenesis and biofilm
      formation. In the BFM, torque is generated at the interface between transmembrane
      proteins (stators) and a rotor. It is well established that the passage of ions
      down a transmembrane gradient through the stator complex provides the energy for
      torque generation. However, the physics involved in this energy conversion remain
      poorly understood. Here we propose a mechanically specific model for torque
      generation in the BFM. In particular, we identify roles for two fundamental
      forces involved in torque generation: electrostatic and steric. We propose that
      electrostatic forces serve to position the stator, whereas steric forces comprise
      the actual "power stroke." Specifically, we propose that ion-induced
      conformational changes about a proline "hinge" residue in a stator alpha-helix
      are directly responsible for generating the power stroke. Our model predictions
      fit well with recent experiments on a single-stator motor. The proposed model
      provides a mechanical explanation for several fundamental properties of the
      flagellar motor, including torque-speed and speed-ion motive force relationships,
      backstepping, variation in step sizes, and the effects of key mutations in the
      stator. 

PMID- 26216960
TI  - Molecular structure of monomorphic peptide fibrils within a kinetically trapped
      hydrogel network.
AB  - Most, if not all, peptide- and protein-based hydrogels formed by self-assembly
      can be characterized as kinetically trapped 3D networks of fibrils. The
      propensity of disease-associated amyloid-forming peptides and proteins to
      assemble into polymorphic fibrils suggests that cross-beta fibrils comprising
      hydrogels may also be polymorphic. We use solid-state NMR to determine the
      molecular and supramolecular structure of MAX1, a de novo designed gel-forming
      peptide, in its fibrillar state. We find that MAX1 adopts a beta-hairpin
      conformation and self-assembles with high fidelity into a double-layered cross
      beta structure. Hairpins assemble with an in-register Syn orientation within each
      beta-sheet layer and with an Anti orientation between layers. Surprisingly,
      although the MAX1 fibril network is kinetically trapped, solid-state NMR data
      show that fibrils within this network are monomorphic and most likely represent
      the thermodynamic ground state. Intermolecular interactions not available in
      alternative structural arrangements apparently dictate this monomorphic behavior.

PMID- 26216961
TI  - Microbiota regulates type 1 diabetes through Toll-like receptors.
AB  - Deletion of the innate immune adaptor myeloid differentiation primary response
      gene 88 (MyD88) in the nonobese diabetic (NOD) mouse model of type 1 diabetes
      (T1D) results in microbiota-dependent protection from the disease: MyD88-negative
      mice in germ-free (GF), but not in specific pathogen-free conditions develop the
      disease. These results could be explained by expansion of particular protective
      bacteria ("specific lineage hypothesis") or by dominance of negative (tolerizing)
      signaling over proinflammatory signaling ("balanced signal hypothesis") in mutant
      mice. Here we found that colonization of GF mice with a variety of intestinal
      bacteria was capable of reducing T1D in MyD88-negative (but not wild-type NOD
      mice), favoring the balanced signal hypothesis. However, the receptors and
      signaling pathways involved in prevention or facilitation of the disease remained
      unknown. The protective signals triggered by the microbiota were revealed by
      testing NOD mice lacking MyD88 in combination with knockouts of several critical
      components of innate immune sensing for development of T1D. Only MyD88- and TIR
      domain containing adapter inducing IFN beta (TRIF) double deficient NOD mice
      developed the disease. Thus, TRIF signaling (likely downstream of Toll-like
      receptor 4, TLR4) serves as one of the microbiota-induced tolerizing pathways. At
      the same time another TLR (TLR2) provided prodiabetic signaling by controlling
      the microbiota, as reduction in T1D incidence caused by TLR2 deletion was
      reversed in GF TLR2-negative mice. Our results support the balanced signal
      hypothesis, in which microbes provide signals that both promote and inhibit
      autoimmunity by signaling through different receptors, including receptors of the
      TLR family. 

PMID- 26216962
TI  - Wiring cost and topological participation of the mouse brain connectome.
AB  - Brain connectomes are topologically complex systems, anatomically embedded in 3D
      space. Anatomical conservation of "wiring cost" explains many but not all aspects
      of these networks. Here, we examined the relationship between topology and wiring
      cost in the mouse connectome by using data from 461 systematically acquired
      anterograde-tracer injections into the right cortical and subcortical regions of
      the mouse brain. We estimated brain-wide weights, distances, and wiring costs of
      axonal projections and performed a multiscale topological and spatial analysis of
      the resulting weighted and directed mouse brain connectome. Our analysis showed
      that the mouse connectome has small-world properties, a hierarchical modular
      structure, and greater-than-minimal wiring costs. High-participation hubs of this
      connectome mediated communication between functionally specialized and
      anatomically localized modules, had especially high wiring costs, and closely
      corresponded to regions of the default mode network. Analyses of independently
      acquired histological and gene-expression data showed that nodal participation
      colocalized with low neuronal density and high expression of genes enriched for
      cognition, learning and memory, and behavior. The mouse connectome contains high
      participation hubs, which are not explained by wiring-cost minimization but
      instead reflect competitive selection pressures for integrated network topology
      as a basis for higher cognitive and behavioral functions. 

PMID- 26216963
TI  - Sequence, structure, and cooperativity in folding of elementary protein
      structural motifs.
AB  - Residue-level unfolding of two helix-turn-helix proteins--one naturally occurring
      and one de novo designed--is reconstructed from multiple sets of site-specific
      (13)C isotopically edited infrared (IR) and circular dichroism (CD) data using
      Ising-like statistical-mechanical models. Several model variants are
      parameterized to test the importance of sequence-specific interactions
      (approximated by Miyazawa-Jernigan statistical potentials), local structural
      flexibility (derived from the ensemble of NMR structures), interhelical hydrogen
      bonds, and native contacts separated by intervening disordered regions (through
      the Wako-Saito-Munoz-Eaton scheme, which disallows such configurations). The
      models are optimized by directly simulating experimental observables: CD
      ellipticity at 222 nm for model proteins and their fragments and (13)C-amide I'
      bands for multiple isotopologues of each protein. We find that data can be
      quantitatively reproduced by the model that allows two interacting segments
      flanking a disordered loop (double sequence approximation) and incorporates
      flexibility in the native contact maps, but neither sequence-specific
      interactions nor hydrogen bonds are required. The near-identical free energy
      profiles as a function of the global order parameter are consistent with expected
      similar folding kinetics for nearly identical structures. However, the predicted
      folding mechanism for the two motifs is different, reflecting the order of local
      stability. We introduce free energy profiles for "experimental" reaction
      coordinates--namely, the degree of local folding as sensed by site-specific (13)C
      edited IR, which highlight folding heterogeneity and contrast its overall,
      average description with the detailed, local picture.

PMID- 26216964
TI  - Highly permeable artificial water channels that can self-assemble into two
      dimensional arrays.
AB  - Bioinspired artificial water channels aim to combine the high permeability and
      selectivity of biological aquaporin (AQP) water channels with chemical stability.
      Here, we carefully characterized a class of artificial water channels, peptide
      appended pillar[5]arenes (PAPs). The average single-channel osmotic water
      permeability for PAPs is 1.0(+/- 0.3) * 10(-14) cm(3)/s or 3.5(+/- 1.0) * 10(8)
      water molecules per s, which is in the range of AQPs (3.4 ~ 40.3 * 10(8) water
      molecules per s) and their current synthetic analogs, carbon nanotubes (CNTs, 9.0
      * 10(8) water molecules per s). This permeability is an order of magnitude higher
      than first-generation artificial water channels (20 to ~ 10(7) water molecules
      per s). Furthermore, within lipid bilayers, PAP channels can self-assemble into
      2D arrays. Relevant to permeable membrane design, the pore density of PAP channel
      arrays (~ 2.6 * 10(5) pores per MUm(2)) is two orders of magnitude higher than
      that of CNT membranes (0.1 ~ 2.5 * 10(3) pores per MUm(2)). PAP channels thus
      combine the advantages of biological channels and CNTs and improve upon them
      through their relatively simple synthesis, chemical stability, and propensity to
      form arrays.

PMID- 26216965
TI  - Accumulation of non-outer segment proteins in the outer segment underlies
      photoreceptor degeneration in Bardet-Biedl syndrome.
AB  - Compartmentalization and polarized protein trafficking are essential for many
      cellular functions. The photoreceptor outer segment (OS) is a sensory compartment
      specialized for phototransduction, and it shares many features with primary
      cilia. As expected, mutations disrupting protein trafficking to cilia often
      disrupt protein trafficking to the OS and cause photoreceptor degeneration.
      Bardet-Biedl syndrome (BBS) is one of the ciliopathies associated with defective
      ciliary trafficking and photoreceptor degeneration. However, precise roles of BBS
      proteins in photoreceptor cells and the underlying mechanisms of photoreceptor
      degeneration in BBS are not well understood. Here, we show that accumulation of
      non-OS proteins in the OS underlies photoreceptor degeneration in BBS. Using a
      newly developed BBS mouse model [Leucine zipper transcription factor-like 1
      (Lztfl1)/Bbs17 mutant], isolated OSs, and quantitative proteomics, we determined
      138 proteins that are enriched more than threefold in BBS mutant OS. In contrast,
      only eight proteins showed a more than threefold reduction. We found striking
      accumulation of Stx3 and Stxbp1/Munc18-1 and loss of polarized localization of
      Prom1 within the Lztfl1 and Bbs1 mutant OS. Ultrastructural analysis revealed
      that large vesicles are formed in the BBS OS, disrupting the lamellar structure
      of the OS. Our findings suggest that accumulation (and consequent sequestration)
      of non-OS proteins in the OS is likely the primary cause of photoreceptor
      degeneration in BBS. Our data also suggest that a major function of BBS proteins
      in photoreceptors is to transport proteins from the OS to the cell body or to
      prevent entry of non-OS proteins into the OS. 

PMID- 26216966
TI  - Divergent evolution of an atypical S-adenosyl-l-methionine-dependent
      monooxygenase involved in anthracycline biosynthesis.
AB  - Bacterial secondary metabolic pathways are responsible for the biosynthesis of
      thousands of bioactive natural products. Many enzymes residing in these pathways
      have evolved to catalyze unusual chemical transformations, which is facilitated
      by an evolutionary pressure promoting chemical diversity. Such divergent enzyme
      evolution has been observed in S-adenosyl-L-methionine (SAM)-dependent
      methyltransferases involved in the biosynthesis of anthracycline anticancer
      antibiotics; whereas DnrK from the daunorubicin pathway is a canonical 4-O
      methyltransferase, the closely related RdmB (52% sequence identity) from the
      rhodomycin pathways is an atypical 10-hydroxylase that requires SAM, a thiol
      reducing agent, and molecular oxygen for activity. Here, we have used extensive
      chimeragenesis to gain insight into the functional differentiation of RdmB and
      show that insertion of a single serine residue to DnrK is sufficient for
      introduction of the monooxygenation activity. The crystal structure of DnrK-Ser
      in complex with aclacinomycin T and S-adenosyl-L-homocysteine refined to 1.9-A
      resolution revealed that the inserted serine S297 resides in an alpha-helical
      segment adjacent to the substrate, but in a manner where the side chain points
      away from the active site. Further experimental work indicated that the shift in
      activity is mediated by rotation of a preceding phenylalanine F296 toward the
      active site, which blocks a channel to the surface of the protein that is present
      in native DnrK. The channel is also closed in RdmB and may be important for
      monooxygenation in a solvent-free environment. Finally, we postulate that the
      hydroxylation ability of RdmB originates from a previously undetected 10
      decarboxylation activity of DnrK.

PMID- 26216967
TI  - Inactive conformation enhances binding function in physiological conditions.
AB  - Many receptors display conformational flexibility, in which the binding pocket
      has an open inactive conformation in the absence of ligand and a tight active
      conformation when bound to ligand. Here we study the bacterial adhesin FimH to
      address the role of the inactive conformation of the pocket for initiating
      binding by comparing two variants: a wild-type FimH variant that is in the
      inactive state when not bound to its target mannose, and an engineered activated
      variant that is always in the active state. Not surprisingly, activated FimH has
      a longer lifetime and higher affinity, and bacteria expressing activated FimH
      bound better in static conditions. However, bacteria expressing wild-type FimH
      bound better in flow. Wild-type and activated FimH demonstrated similar
      mechanical strength, likely because mechanical force induces the active state in
      wild-type FimH. However, wild-type FimH displayed a faster bond association rate
      than activated FimH. Moreover, the ability of different FimH variants to mediate
      adhesion in flow reflected the fraction of FimH in the inactive state. These
      results demonstrate a new model for ligand-associated conformational changes that
      we call the kinetic-selection model, in which ligand-binding selects the faster
      binding inactive state and then induces the active state. This model predicts
      that in physiological conditions for cell adhesion, mechanical force will drive a
      nonequilibrium cycle that uses the fast binding rate of the inactive state and
      slow unbinding rate of the active state, for a higher effective affinity than is
      possible at equilibrium. 

PMID- 26216968
TI  - Generation of MANAbodies specific to HLA-restricted epitopes encoded by
      somatically mutated genes.
AB  - Mutant epitopes encoded by cancer genes are virtually always located in the
      interior of cells, making them invisible to conventional antibodies. We here
      describe an approach to identify single-chain variable fragments (scFvs) specific
      for mutant peptides presented on the cell surface by HLA molecules. We
      demonstrate that these scFvs can be successfully converted to full-length
      antibodies, termed MANAbodies, targeting "Mutation-Associated Neo-Antigens" bound
      to HLA. A phage display library representing a highly diverse array of single
      chain variable fragment sequences was first designed and constructed. A
      competitive selection protocol was then used to identify clones specific for
      mutant peptides bound to predefined HLA types. In this way, we obtained two
      scFvs, one specific for a peptide encoded by a common KRAS mutant and the other
      by a common epidermal growth factor receptor (EGFR) mutant. The scFvs bound to
      these peptides only when the peptides were complexed with HLA-A2 (KRAS peptide)
      or HLA-A3 (EGFR peptide). We converted one scFv to a full-length antibody
      (MANAbody) and demonstrate that the MANAbody specifically reacts with mutant
      peptide-HLA complex even when the peptide differs by only one amino acid from the
      normal, WT form. 

PMID- 26216969
TI  - Structural basis for inhibition of the histone chaperone activity of SET/TAF
      Ibeta by cytochrome c.
AB  - Chromatin is pivotal for regulation of the DNA damage process insofar as it
      influences access to DNA and serves as a DNA repair docking site. Recent works
      identify histone chaperones as key regulators of damaged chromatin's
      transcriptional activity. However, understanding how chaperones are modulated
      during DNA damage response is still challenging. This study reveals that the
      histone chaperone SET/TAF-Ibeta interacts with cytochrome c following DNA damage.
      Specifically, cytochrome c is shown to be translocated into cell nuclei upon
      induction of DNA damage, but not upon stimulation of the death receptor or stress
      induced pathways. Cytochrome c was found to competitively hinder binding of
      SET/TAF-Ibeta to core histones, thereby locking its histone-binding domains and
      inhibiting its nucleosome assembly activity. In addition, we have used NMR
      spectroscopy, calorimetry, mutagenesis, and molecular docking to provide an
      insight into the structural features of the formation of the complex between
      cytochrome c and SET/TAF-Ibeta. Overall, these findings establish a framework for
      understanding the molecular basis of cytochrome c-mediated blocking of SET/TAF
      Ibeta, which subsequently may facilitate the development of new drugs to silence
      the oncogenic effect of SET/TAF-Ibeta's histone chaperone activity. 

PMID- 26216971
TI  - Efficient method to optimize antibodies using avian leukosis virus display and
      eukaryotic cells.
AB  - Antibody-based therapeutics have now had success in the clinic. The affinity and
      specificity of the antibody for the target ligand determines the specificity of
      therapeutic delivery and off-target side effects. The discovery and optimization
      of high-affinity antibodies to important therapeutic targets could be
      significantly improved by the availability of a robust, eukaryotic display
      technology comparable to phage display that would overcome the protein
      translation limitations of microorganisms. The use of eukaryotic cells would
      improve the diversity of the displayed antibodies that can be screened and
      optimized as well as more seamlessly transition into a large-scale mammalian
      expression system for clinical production. In this study, we demonstrate that the
      replication and polypeptide display characteristics of a eukaryotic retrovirus,
      avian leukosis virus (ALV), offers a robust, eukaryotic version of bacteriophage
      display. The binding affinity of a model single-chain Fv antibody was optimized
      by using ALV display, improving affinity >2,000-fold, from micromolar to
      picomolar levels. We believe ALV display provides an extension to antibody
      display on microorganisms and offers virus and cell display platforms in a
      eukaryotic expression system. ALV display should enable an improvement in the
      diversity of properly processed and functional antibody variants that can be
      screened and affinity-optimized to improve promising antibody candidates. 

PMID- 26216970
TI  - Synaptotagmin-7 phosphorylation mediates GLP-1-dependent potentiation of insulin
      secretion from beta-cells.
AB  - Glucose stimulates insulin secretion from beta-cells by increasing intracellular
      Ca(2+). Ca(2+) then binds to synaptotagmin-7 as a major Ca(2+) sensor for
      exocytosis, triggering secretory granule fusion and insulin secretion. In type-2
      diabetes, insulin secretion is impaired; this impairment is ameliorated by
      glucagon-like peptide-1 (GLP-1) or by GLP-1 receptor agonists, which improve
      glucose homeostasis. However, the mechanism by which GLP-1 receptor agonists
      boost insulin secretion remains unclear. Here, we report that GLP-1 stimulates
      protein kinase A (PKA)-dependent phosphorylation of synaptotagmin-7 at serine
      103, which enhances glucose- and Ca(2+)-stimulated insulin secretion and accounts
      for the improvement of glucose homeostasis by GLP-1. A phospho-mimetic
      synaptotagmin-7 mutant enhances Ca(2+)-triggered exocytosis, whereas a phospho
      inactive synaptotagmin-7 mutant disrupts GLP-1 potentiation of insulin secretion.
      Our findings thus suggest that synaptotagmin-7 is directly activated by GLP-1
      signaling and may serve as a drug target for boosting insulin secretion.
      Moreover, our data reveal, to our knowledge, the first physiological modulation
      of Ca(2+)-triggered exocytosis by direct phosphorylation of a synaptotagmin. 

PMID- 26216972
TI  - Reconstitution of TCA cycle with DAOCS to engineer Escherichia coli into an
      efficient whole cell catalyst of penicillin G.
AB  - Many medically useful semisynthetic cephalosporins are derived from 7
      aminodeacetoxycephalosporanic acid (7-ADCA), which has been traditionally made by
      the polluting chemical method. Here, a whole-cell biocatalytic process based on
      an engineered Escherichia coli strain expressing 2-oxoglutarate-dependent
      deacetoxycephalosporin C synthase (DAOCS) for converting penicillin G to G-7-ADCA
      is developed. The major engineering strategy is to reconstitute the tricarboxylic
      acid (TCA) cycle of E. coli to force the metabolic flux to go through DAOCS
      catalyzed reaction for 2-oxoglutarate to succinate conversion. Then the
      glyoxylate bypass was disrupted to eliminate metabolic flux that may circumvent
      the reconstituted TCA cycle. Additional engineering steps were taken to reduce
      the degradation of penicillin G and G-7-ADCA in the bioconversion process. These
      steps include engineering strategies to reduce acetate accumulation in the
      biocatalytic process and to knock out a host beta-lactamase involved in the
      degradation of penicillin G and G-7-ADCA. By combining these manipulations in an
      engineered strain, the yield of G-7-ADCA was increased from 2.50 +/- 0.79 mM
      (0.89 +/- 0.28 g/L, 0.07 +/- 0.02 g/gDCW) to 29.01 +/- 1.27 mM (10.31 +/- 0.46
      g/L, 0.77 +/- 0.03 g/gDCW) with a conversion rate of 29.01 mol%, representing an
      11-fold increase compared with the starting strain (2.50 mol%). 

PMID- 26216973
TI  - Single-cell measurement of red blood cell oxygen affinity.
AB  - Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells
      (RBCs). Although the oxygen affinity of blood is well-understood and routinely
      assessed in patients by pulse oximetry, variability at the single-cell level has
      not been previously measured. In contrast, single-cell measurements of RBC volume
      and Hb concentration are taken millions of times per day by clinical hematology
      analyzers, and they are important factors in determining the health of the
      hematologic system. To better understand the variability and determinants of
      oxygen affinity on a cellular level, we have developed a system that quantifies
      the oxygen saturation, cell volume, and Hb concentration for individual RBCs in
      high throughput. We find that the variability in single-cell saturation peaks at
      an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the
      oxygen-Hb dissociation curve. In addition, single-cell oxygen affinity is
      positively correlated with Hb concentration but independent of osmolarity, which
      suggests variation in the Hb to 2,3-diphosphoglycerate (2-3 DPG) ratio on a
      cellular level. By quantifying the functional behavior of a cellular population,
      our system adds a dimension to blood cell analysis and other measurements of
      single-cell variability. 

PMID- 26216975
TI  - Discrete approach to stochastic parametrization and dimension reduction in
      nonlinear dynamics.
AB  - Many physical systems are described by nonlinear differential equations that are
      too complicated to solve in full. A natural way to proceed is to divide the
      variables into those that are of direct interest and those that are not,
      formulate solvable approximate equations for the variables of greater interest,
      and use data and statistical methods to account for the impact of the other
      variables. In the present paper we consider time-dependent problems and introduce
      a fully discrete solution method, which simplifies both the analysis of the data
      and the numerical algorithms. The resulting time series are identified by a
      NARMAX (nonlinear autoregression moving average with exogenous input)
      representation familiar from engineering practice. The connections with the Mori
      Zwanzig formalism of statistical physics are discussed, as well as an application
      to the Lorenz 96 system. 

PMID- 26216974
TI  - Prophylactic and postexposure efficacy of a potent human monoclonal antibody
      against MERS coronavirus.
AB  - Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection
      caused by a previously unidentified coronavirus (CoV), likely transmitted to
      humans by infected camels. There is no licensed vaccine or antiviral for MERS,
      therefore new prophylactic and therapeutic strategies to combat human infections
      are needed. In this study, we describe, for the first time, to our knowledge, the
      isolation of a potent MERS-CoV-neutralizing antibody from memory B cells of an
      infected individual. The antibody, named LCA60, binds to a novel site on the
      spike protein and potently neutralizes infection of multiple MERS-CoV isolates by
      interfering with the binding to the cellular receptor CD26. Importantly, using
      mice transduced with adenovirus expressing human CD26 and infected with MERS-CoV,
      we show that LCA60 can effectively protect in both prophylactic and postexposure
      settings. This antibody can be used for prophylaxis, for postexposure prophylaxis
      of individuals at risk, or for the treatment of human cases of MERS-CoV
      infection. The fact that it took only 4 mo from the initial screening of B cells
      derived from a convalescent patient for the development of a stable chinese
      hamster ovary (CHO) cell line producing neutralizing antibodies at more than 5
      g/L provides an example of a rapid pathway toward the generation of effective
      antiviral therapies against emerging viruses. 

PMID- 26216976
TI  - Amber fossils demonstrate deep-time stability of Caribbean lizard communities.
AB  - Whether the structure of ecological communities can exhibit stability over
      macroevolutionary timescales has long been debated. The similarity of
      independently evolved Anolis lizard communities on environmentally similar
      Greater Antillean islands supports the notion that community evolution is
      deterministic. However, a dearth of Caribbean Anolis fossils--only three have
      been described to date--has precluded direct investigation of the stability of
      anole communities through time. Here we report on an additional 17 fossil anoles
      in Dominican amber dating to 15-20 My before the present. Using data collected
      primarily by X-ray microcomputed tomography (X-ray micro-CT), we demonstrate that
      the main elements of Hispaniolan anole ecomorphological diversity were in place
      in the Miocene. Phylogenetic analysis yields results consistent with the
      hypothesis that the ecomorphs that evolved in the Miocene are members of the same
      ecomorph clades extant today. The primary axes of ecomorphological diversity in
      the Hispaniolan anole fauna appear to have changed little between the Miocene and
      the present, providing evidence for the stability of ecological communities over
      macroevolutionary timescales.

PMID- 26216977
TI  - Baculovirus protein PK2 subverts eIF2alpha kinase function by mimicry of its
      kinase domain C-lobe.
AB  - Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) by
      eIF2alpha family kinases is a conserved mechanism to limit protein synthesis
      under specific stress conditions. The baculovirus-encoded protein PK2 inhibits
      eIF2alpha family kinases in vivo, thereby increasing viral fitness. However, the
      precise mechanism by which PK2 inhibits eIF2alpha kinase function remains an
      enigma. Here, we probed the mechanism by which PK2 inhibits the model eIF2alpha
      kinase human RNA-dependent protein kinase (PKR) as well as native insect
      eIF2alpha kinases. Although PK2 structurally mimics the C-lobe of a protein
      kinase domain and possesses the required docking infrastructure to bind
      eIF2alpha, we show that PK2 directly binds the kinase domain of PKR (PKR(KD)) but
      not eIF2alpha. The PKR(KD)-PK2 interaction requires a 22-residue N-terminal
      extension preceding the globular PK2 body that we term the "eIF2alpha kinase C
      lobe mimic" (EKCM) domain. The functional insufficiency of the N-terminal
      extension of PK2 implicates a role for the adjacent EKCM domain in binding and
      inhibiting PKR. Using a genetic screen in yeast, we isolated PK2-activating
      mutations that cluster to a surface of the EKCM domain that in bona fide protein
      kinases forms the catalytic cleft through sandwiching interactions with a kinase
      N-lobe. Interaction assays revealed that PK2 associates with the N- but not the C
      lobe of PKR(KD). We propose an inhibitory model whereby PK2 engages the N-lobe of
      an eIF2alpha kinase domain to create a nonfunctional pseudokinase domain complex,
      possibly through a lobe-swapping mechanism. Finally, we show that PK2 enhances
      baculovirus fitness in insect hosts by targeting the endogenous insect heme
      regulated inhibitor (HRI)-like eIF2alpha kinase. 

PMID- 26216978
TI  - Orthologs of the archaeal isopentenyl phosphate kinase regulate terpenoid
      production in plants.
AB  - Terpenoids, compounds found in all domains of life, represent the largest class
      of natural products with essential roles in their hosts. All terpenoids originate
      from the five-carbon building blocks, isopentenyl diphosphate (IPP) and its
      isomer dimethylallyl diphosphate (DMAPP), which can be derived from the mevalonic
      acid (MVA) and methylerythritol phosphate (MEP) pathways. The absence of two
      components of the MVA pathway from archaeal genomes led to the discovery of an
      alternative MVA pathway with isopentenyl phosphate kinase (IPK) catalyzing the
      final step, the formation of IPP. Despite the fact that plants contain the
      complete classical MVA pathway, IPK homologs were identified in every sequenced
      green plant genome. Here, we show that IPK is indeed a member of the plant
      terpenoid metabolic network. It is localized in the cytosol and is coexpressed
      with MVA pathway and downstream terpenoid network genes. In planta, IPK acts in
      parallel with the MVA pathway and plays an important role in regulating the
      formation of both MVA and MEP pathway-derived terpenoid compounds by controlling
      the ratio of IP/DMAP to IPP/DMAPP. IP and DMAP can also competitively inhibit
      farnesyl diphosphate synthase. Moreover, we discovered a metabolically available
      carbon source for terpenoid formation in plants that is accessible via IPK
      overexpression. This metabolite reactivation approach offers new strategies for
      metabolic engineering of terpenoid production. 

PMID- 26216979
TI  - GRIP1 is required for homeostatic regulation of AMPAR trafficking.
AB  - Homeostatic plasticity is a negative feedback mechanism that stabilizes neurons
      during periods of perturbed activity. The best-studied form of homeostatic
      plasticity in the central nervous system is the scaling of excitatory synapses.
      Postsynaptic AMPA-type glutamate receptors (AMPARs) can be inserted into synapses
      to compensate for neuronal inactivity or removed to compensate for hyperactivity.
      However, the molecular mechanisms underlying the homeostatic regulation of AMPARs
      remain elusive. Here, we show that the expression of GRIP1, a multi-PDZ
      (postsynaptic density 95/discs large/zona occludens) domain AMPAR-binding
      protein, is bidirectionally altered by neuronal activity. Furthermore, we observe
      a subcellular redistribution of GRIP1 and a change in the binding of GRIP1 to
      GluA2 during synaptic scaling. Using a combination of biochemical, genetic, and
      electrophysiological methods, we find that loss of GRIP1 blocks the accumulation
      of surface AMPARs and the scaling up of synaptic strength that occur in response
      to chronic activity blockade. Collectively, our data point to an essential role
      of GRIP1-mediated AMPAR trafficking during inactivity-induced synaptic scaling. 

PMID- 26216980
TI  - Sinuous flow in metals.
AB  - Annealed metals are surprisingly difficult to cut, involving high forces and an
      unusually thick "chip." This anomaly has long been explained, based on ex situ
      observations, using a model of smooth plastic flow with uniform shear to describe
      material removal by chip formation. Here we show that this phenomenon is actually
      the result of a fundamentally different collective deformation mode--sinuous
      flow. Using in situ imaging, we find that chip formation occurs via large
      amplitude folding, triggered by surface undulations of a characteristic size. The
      resulting fold patterns resemble those observed in geophysics and complex fluids.
      Our observations establish sinuous flow as another mesoscopic deformation mode,
      alongside mechanisms such as kinking and shear banding. Additionally, by
      suppressing the triggering surface undulations, sinuous flow can be eliminated,
      resulting in a drastic reduction of cutting forces. We demonstrate this
      suppression quite simply by the application of common marking ink on the free
      surface of the workpiece material before the cutting. Alternatively, prehardening
      a thin surface layer of the workpiece material shows similar results. Besides
      obvious implications to industrial machining and surface generation processes,
      our results also help unify a number of disparate observations in the cutting of
      metals, including the so-called Rehbinder effect.

PMID- 26216981
TI  - Bayesian chronological analyses consistent with synchronous age of 12,835-12,735
      Cal B.P. for Younger Dryas boundary on four continents.
AB  - The Younger Dryas impact hypothesis posits that a cosmic impact across much of
      the Northern Hemisphere deposited the Younger Dryas boundary (YDB) layer,
      containing peak abundances in a variable assemblage of proxies, including
      magnetic and glassy impact-related spherules, high-temperature minerals and melt
      glass, nanodiamonds, carbon spherules, aciniform carbon, platinum, and osmium.
      Bayesian chronological modeling was applied to 354 dates from 23 stratigraphic
      sections in 12 countries on four continents to establish a modeled YDB age range
      for this event of 12,835-12,735 Cal B.P. at 95% probability. This range overlaps
      that of a peak in extraterrestrial platinum in the Greenland Ice Sheet and of the
      earliest age of the Younger Dryas climate episode in six proxy records,
      suggesting a causal connection between the YDB impact event and the Younger
      Dryas. Two statistical tests indicate that both modeled and unmodeled ages in the
      30 records are consistent with synchronous deposition of the YDB layer within the
      limits of dating uncertainty (~ 100 y). The widespread distribution of the YDB
      layer suggests that it may serve as a datum layer.

PMID- 26216982
TI  - Irwin Rose (1926-2015).

PMID- 26216983
TI  - Coexistence of Y, W, and Z sex chromosomes in Xenopus tropicalis.
AB  - Homomorphic sex chromosomes and rapid turnover of sex-determining genes can
      complicate establishing the sex chromosome system operating in a given species.
      This difficulty exists in Xenopus tropicalis, an anuran quickly becoming a
      relevant model for genetic, genomic, biochemical, and ecotoxicological research.
      Despite the recent interest attracted by this species, little is known about its
      sex chromosome system. Direct evidence that females are the heterogametic sex, as
      in the related species Xenopus laevis, has yet to be presented. Furthermore, X.
      laevis' sex-determining gene, DM-W, does not exist in X. tropicalis, and the sex
      chromosomes in the two species are not homologous. Here we identify X.
      tropicalis' sex chromosome system by integrating data from (i) breeding sex
      reversed individuals, (ii) gynogenesis, (iii) triploids, and (iv) crosses among
      several strains. Our results indicate that at least three different types of sex
      chromosomes exist: Y, W, and Z, observed in YZ, YW, and ZZ males and in ZW and WW
      females. Because some combinations of parental sex chromosomes produce unisex
      offspring and other distorted sex ratios, understanding the sex-determination
      systems in X. tropicalis is critical for developing this flexible animal model
      for genetics and ecotoxicology. 

PMID- 26216984
TI  - Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes
      with distinct sensitivities to metabolic inhibitors.
AB  - Although targeting cancer metabolism is a promising therapeutic strategy,
      clinical success will depend on an accurate diagnostic identification of tumor
      subtypes with specific metabolic requirements. Through broad metabolite
      profiling, we successfully identified three highly distinct metabolic subtypes in
      pancreatic ductal adenocarcinoma (PDAC). One subtype was defined by reduced
      proliferative capacity, whereas the other two subtypes (glycolytic and lipogenic)
      showed distinct metabolite levels associated with glycolysis, lipogenesis, and
      redox pathways, confirmed at the transcriptional level. The glycolytic and
      lipogenic subtypes showed striking differences in glucose and glutamine
      utilization, as well as mitochondrial function, and corresponded to differences
      in cell sensitivity to inhibitors of glycolysis, glutamine metabolism, lipid
      synthesis, and redox balance. In PDAC clinical samples, the lipogenic subtype
      associated with the epithelial (classical) subtype, whereas the glycolytic
      subtype strongly associated with the mesenchymal (QM-PDA) subtype, suggesting
      functional relevance in disease progression. Pharmacogenomic screening of an
      additional ~ 200 non-PDAC cell lines validated the association between
      mesenchymal status and metabolic drug response in other tumor indications. Our
      findings highlight the utility of broad metabolite profiling to predict
      sensitivity of tumors to a variety of metabolic inhibitors.

PMID- 26216985
TI  - Flexible brain network reconfiguration supporting inhibitory control.
AB  - The ability to inhibit distracting stimuli from interfering with goal-directed
      behavior is crucial for success in most spheres of life. Despite an abundance of
      studies examining regional brain activation, knowledge of the brain networks
      involved in inhibitory control remains quite limited. To address this critical
      gap, we applied graph theory tools to functional magnetic resonance imaging data
      collected while a large sample of adults (n = 101) performed a color-word Stroop
      task. Higher demand for inhibitory control was associated with restructuring of
      the global network into a configuration that was more optimized for specialized
      processing (functional segregation), more efficient at communicating the output
      of such processing across the network (functional integration), and more
      resilient to potential interruption (resilience). In addition, there were
      regional changes with right inferior frontal sulcus and right anterior insula
      occupying more central positions as network hubs, and dorsal anterior cingulate
      cortex becoming more tightly coupled with its regional subnetwork. Given the
      crucial role of inhibitory control in goal-directed behavior, present findings
      identifying functional network organization supporting inhibitory control have
      the potential to provide additional insights into how inhibitory control may
      break down in a wide variety of individuals with neurological or psychiatric
      difficulties. 

PMID- 26216986
TI  - Socially mediated induction and suppression of antibiosis during bacterial
      coexistence.
AB  - Despite their importance for humans, there is little consensus on the function of
      antibiotics in nature for the bacteria that produce them. Classical explanations
      suggest that bacteria use antibiotics as weapons to kill or inhibit competitors,
      whereas a recent alternative hypothesis states that antibiotics are signals that
      coordinate cooperative social interactions between coexisting bacteria. Here we
      distinguish these hypotheses in the prolific antibiotic-producing genus
      Streptomyces and provide strong evidence that antibiotics are weapons whose
      expression is significantly influenced by social and competitive interactions
      between competing strains. We show that cells induce facultative responses to
      cues produced by competitors by (i) increasing their own antibiotic production,
      thereby decreasing costs associated with constitutive synthesis of these
      expensive products, and (ii) by suppressing antibiotic production in competitors,
      thereby reducing direct threats to themselves. These results thus show that
      although antibiotic production is profoundly social, it is emphatically not
      cooperative. Using computer simulations, we next show that these facultative
      strategies can facilitate the maintenance of biodiversity in a community context
      by converting lethal interactions between neighboring colonies to neutral
      interactions where neither strain excludes the other. Thus, just as bacteriocins
      can lead to increased diversity via rock-paper-scissors dynamics, so too can
      antibiotics via elicitation and suppression. Our results reveal that social
      interactions are crucial for understanding antibiosis and bacterial community
      dynamics, and highlight the potential of interbacterial interactions for novel
      drug discovery by eliciting pathways that mediate interference competition. 

PMID- 26216987
TI  - Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination.
AB  - Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the
      UBE3A gene has been associated with three different clinical pictures. Hijacking
      of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV)
      contributes to the development of cervical cancer, whereas loss of E6AP
      expression or function is the cause of Angelman syndrome, a neurodevelopmental
      disorder, and increased expression of E6AP has been involved in autism spectrum
      disorders. Although these observations indicate that the activity of E6AP has to
      be tightly controlled, only little is known about how E6AP is regulated at the
      posttranslational level. Here, we provide evidence that the hydrophobic patch of
      ubiquitin comprising Leu-8 and Ile-44 is important for E6AP-mediated
      ubiquitination, whereas it does not affect the catalytic properties of the
      isolated catalytic HECT domain of E6AP. Furthermore, we show that the HPV E6
      oncoprotein rescues the disability of full-length E6AP to use a respective
      hydrophobic patch mutant of ubiquitin for ubiquitination and that it stimulates
      E6AP-mediated ubiquitination of Ring1B, a known substrate of E6AP, in vitro and
      in cells. Based on these data, we propose that E6AP exists in at least two
      different states, an active and a less active or latent one, and that the
      activity of E6AP is controlled by noncovalent interactions with ubiquitin and
      allosteric activators such as the HPV E6 oncoprotein. 

PMID- 26216988
TI  - Gating of a mechanosensitive channel due to cellular flows.
AB  - A multiscale continuum model is constructed for a mechanosensitive (MS) channel
      gated by tension in a lipid bilayer membrane under stresses due to fluid flows.
      We illustrate that for typical physiological conditions vesicle hydrodynamics
      driven by a fluid flow may render the membrane tension sufficiently large to gate
      a MS channel open. In particular, we focus on the dynamic opening/closing of a MS
      channel in a vesicle membrane under a planar shear flow and a pressure-driven
      flow across a constriction channel. Our modeling and numerical simulation results
      quantify the critical flow strength or flow channel geometry for intracellular
      transport through a MS channel. In particular, we determine the percentage of MS
      channels that are open or closed as a function of the relevant measure of flow
      strength. The modeling and simulation results imply that for fluid flows that are
      physiologically relevant and realizable in microfluidic configurations stress
      induced intracellular transport across the lipid membrane can be achieved by the
      gating of reconstituted MS channels, which can be useful for designing drug
      delivery in medical therapy and understanding complicated mechanotransduction. 

PMID- 26216989
TI  - Divergent responses of Atlantic coastal and oceanic Synechococcus to iron
      limitation.
AB  - Marine Synechococcus are some of the most diverse and ubiquitous phytoplankton,
      and iron (Fe) is an essential micronutrient that limits productivity in many
      parts of the ocean. To investigate how coastal and oceanic Atlantic Synechococcus
      strains acclimate to Fe availability, we compared the growth, photophysiology,
      and quantitative proteomics of two Synechococcus strains from different Fe
      regimes. Synechococcus strain WH8102, from a region in the southern Sargasso Sea
      that receives substantial dust deposition, showed impaired growth and
      photophysiology as Fe declined, yet used few acclimation responses. Coastal
      WH8020, from the dynamic, seasonally variable New England shelf, displayed a
      multitiered, hierarchical cascade of acclimation responses with different Fe
      thresholds. The multitiered response included changes in Fe acquisition, storage,
      and photosynthetic proteins, substitution of flavodoxin for ferredoxin, and
      modified photophysiology, all while maintaining remarkably stable growth rates
      over a range of Fe concentrations. Modulation of two distinct ferric uptake
      regulator (Fur) proteins that coincided with the multitiered proteome response
      was found, implying the coastal strain has different regulatory threshold
      responses to low Fe availability. Low nitrogen (N) and phosphorus (P)
      availability in the open ocean may favor the loss of Fe response genes when Fe
      availability is consistent over time, whereas these genes are retained in dynamic
      environments where Fe availability fluctuates and N and P are more abundant. 

PMID- 26216990
TI  - Splicing inhibition of U2AF65 leads to alternative exon skipping.
AB  - U2 snRNP auxiliary factor 65 kDa (U2AF(65)) is a general splicing factor that
      contacts polypyrimidine (Py) tract and promotes prespliceosome assembly. In this
      report, we show that U2AF(65) stimulates alternative exon skipping in spinal
      muscular atrophy (SMA)-related survival motor neuron (SMN) pre-mRNA. A stronger
      5' splice-site mutation of alternative exon abolishes the stimulatory effects of
      U2AF(65). U2AF(65) overexpression promotes its own binding only on the weaker,
      not the stronger, Py tract. We further demonstrate that U2AF(65) inhibits
      splicing of flanking introns of alternative exon in both three-exon and two-exon
      contexts. Similar U2AF(65) effects were observed in Fas (Apo-1/CD95) pre-mRNA.
      Strikingly, we demonstrate that U2AF(65) even inhibits general splicing of
      adenovirus major late (Ad ML) or beta-globin pre-mRNA. Thus, we conclude that
      U2AF(65) possesses a splicing Inhibitory function that leads to alternative exon
      skipping. 

PMID- 26216991
TI  - Rational design of antibodies targeting specific epitopes within intrinsically
      disordered proteins.
AB  - Antibodies are powerful tools in life sciences research, as well as in diagnostic
      and therapeutic applications, because of their ability to bind given molecules
      with high affinity and specificity. Using current methods, however, it is
      laborious and sometimes difficult to generate antibodies to target specific
      epitopes within a protein, in particular if these epitopes are not effective
      antigens. Here we present a method to rationally design antibodies to enable them
      to bind virtually any chosen disordered epitope in a protein. The procedure
      consists in the sequence-based design of one or more complementary peptides
      targeting a selected disordered epitope and the subsequent grafting of such
      peptides on an antibody scaffold. We illustrate the method by designing six
      single-domain antibodies to bind different epitopes within three disease-related
      intrinsically disordered proteins and peptides (alpha-synuclein, Abeta42, and
      IAPP). Our results show that all these designed antibodies bind their targets
      with good affinity and specificity. As an example of an application, we show that
      one of these antibodies inhibits the aggregation of alpha-synuclein at
      substoichiometric concentrations and that binding occurs at the selected epitope.
      Taken together, these results indicate that the design strategy that we propose
      makes it possible to obtain antibodies targeting given epitopes in disordered
      proteins or protein regions. 

PMID- 26216992
TI  - Brd4 bridges the transcriptional regulators, Aire and P-TEFb, to promote
      elongation of peripheral-tissue antigen transcripts in thymic stromal cells.
AB  - Aire controls immunologic tolerance by inducing a battery of thymic transcripts
      encoding proteins characteristic of peripheral tissues. Its unusually broad
      effect is achieved by releasing RNA polymerase II paused just downstream of
      transcriptional start sites. We explored Aire's collaboration with the
      bromodomain-containing protein, Brd4, uncovering an astonishing correspondence
      between those genes induced by Aire and those inhibited by a small-molecule
      bromodomain blocker. Aire:Brd4 binding depended on an orchestrated series of
      posttranslational modifications within Aire's caspase activation and recruitment
      domain. This interaction attracted P-TEFb, thereby mobilizing downstream
      transcriptional elongation and splicing machineries. Aire:Brd4 association was
      critical for tolerance induction, and its disruption could account for certain
      point mutations that provoke human autoimmune disease. Our findings evoke the
      possibility of unanticipated immunologic mechanisms subtending the potent
      antitumor effects of bromodomain blockers. 

PMID- 26216994
TI  - Indirect nitrous oxide emissions from streams within the US Corn Belt scale with
      stream order.
AB  - N2O is an important greenhouse gas and the primary stratospheric ozone depleting
      substance. Its deleterious effects on the environment have prompted appeals to
      regulate emissions from agriculture, which represents the primary anthropogenic
      source in the global N2O budget. Successful implementation of mitigation
      strategies requires robust bottom-up inventories that are based on emission
      factors (EFs), simulation models, or a combination of the two. Top-down emission
      estimates, based on tall-tower and aircraft observations, indicate that bottom-up
      inventories severely underestimate regional and continental scale N2O emissions,
      implying that EFs may be biased low. Here, we measured N2O emissions from streams
      within the US Corn Belt using a chamber-based approach and analyzed the data as a
      function of Strahler stream order (S). N2O fluxes from headwater streams often
      exceeded 29 nmol N2O-N m(-2) ? s(-1) and decreased exponentially as a function of
      S. This relation was used to scale up riverine emissions and to assess the
      differences between bottom-up and top-down emission inventories at the local to
      regional scale. We found that the Intergovernmental Panel on Climate Change
      (IPCC) indirect EF for rivers (EF5r) is underestimated up to ninefold in southern
      Minnesota, which translates to a total tier 1 agricultural underestimation of N2O
      emissions by 40%. We show that accounting for zero-order streams as potential N2O
      hotspots can more than double the agricultural budget. Applying the same analysis
      to the US Corn Belt demonstrates that the IPCC EF5r underestimation explains the
      large differences observed between top-down and bottom-up emission estimates.

PMID- 26216993
TI  - Novel serologic biomarkers provide accurate estimates of recent Plasmodium
      falciparum exposure for individuals and communities.
AB  - Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and
      communities are needed to guide and evaluate malaria control interventions.
      Serologic assays can potentially produce precise exposure estimates at low cost;
      however, current approaches based on responses to a few characterized antigens
      are not designed to estimate exposure in individuals. Pf-specific antibody
      responses differ by antigen, suggesting that selection of antigens with defined
      kinetic profiles will improve estimates of Pf exposure. To identify novel
      serologic biomarkers of malaria exposure, we evaluated responses to 856 Pf
      antigens by protein microarray in 186 Ugandan children, for whom detailed Pf
      exposure data were available. Using data-adaptive statistical methods, we
      identified combinations of antibody responses that maximized information on an
      individual's recent exposure. Responses to three novel Pf antigens accurately
      classified whether an individual had been infected within the last 30, 90, or 365
      d (cross-validated area under the curve = 0.86-0.93), whereas responses to six
      antigens accurately estimated an individual's malaria incidence in the prior
      year. Cross-validated incidence predictions for individuals in different
      communities provided accurate stratification of exposure between populations and
      suggest that precise estimates of community exposure can be obtained from
      sampling a small subset of that community. In addition, serologic incidence
      predictions from cross-sectional samples characterized heterogeneity within a
      community similarly to 1 y of continuous passive surveillance. Development of
      simple ELISA-based assays derived from the successful selection strategy outlined
      here offers the potential to generate rich epidemiologic surveillance data that
      will be widely accessible to malaria control programs. 

PMID- 26216995
TI  - Action potentials and amphetamine release antipsychotic drug from dopamine neuron
      synaptic VMAT vesicles.
AB  - Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic
      drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping
      and to be released in response to action potentials. Because many APDs are
      dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be
      particularly interesting if it operated in midbrain DA neurons. Here, the APD
      cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia
      nigra and striatum brain slices. CYAM accumulated slowly into puncta based on
      vacuolar H(+)-ATPase activity and dispersed rapidly upon dissipating organelle pH
      gradients. Thus, CYAM is subject to acidic trapping and released upon
      deprotonation. In the striatum, Ca(2+)-dependent reduction of the CYAM punctate
      signal was induced by depolarization or action potentials. Striatal CYAM
      overlapped with the dopamine transporter (DAT). Furthermore,
      parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT),
      and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP(+)), reduced
      striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed
      that clinically relevant CYAM concentrations result in vesicular accumulation and
      pCA-dependent release. These results show that some CYAM is in DA neuron VMAT
      vesicles and suggests a new drug interaction in which amphetamine induces CYAM
      deprotonation and release as a consequence of the H(+) countertransport by VMAT
      that accompanies vesicular uptake, but not by inducing exchange or acting as a
      weak base. Therefore, in the striatum, APDs are released with DA in response to
      action potentials and an amphetamine. This synaptic corelease is expected to
      enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs. 

PMID- 26216996
TI  - Enlightening the photoactive site of channelrhodopsin-2 by DNP-enhanced solid
      state NMR spectroscopy.
AB  - Channelrhodopsin-2 from Chlamydomonas reinhardtii is a light-gated ion channel.
      Over recent years, this ion channel has attracted considerable interest because
      of its unparalleled role in optogenetic applications. However, despite
      considerable efforts, an understanding of how molecular events during the
      photocycle, including the retinal trans-cis isomerization and the
      deprotonation/reprotonation of the Schiff base, are coupled to the channel
      opening mechanism remains elusive. To elucidate this question, changes of
      conformation and configuration of several photocycle and conducting/nonconducting
      states need to be determined at atomic resolution. Here, we show that such data
      can be obtained by solid-state NMR enhanced by dynamic nuclear polarization
      applied to (15)N-labeled channelrhodopsin-2 carrying 14,15-(13)C2 retinal
      reconstituted into lipid bilayers. In its dark state, a pure all-trans retinal
      conformation with a stretched C14-C15 bond and a significant out-of-plane twist
      of the H-C14-C15-H dihedral angle could be observed. Using a combination of
      illumination, freezing, and thermal relaxation procedures, a number of
      intermediate states was generated and analyzed by DNP-enhanced solid-state NMR.
      Three distinct intermediates could be analyzed with high structural resolution:
      the early [Formula: see text] K-like state, the slowly decaying late intermediate
      [Formula: see text], and a third intermediate populated only under continuous
      illumination conditions. Our data provide novel insight into the photoactive site
      of channelrhodopsin-2 during the photocycle. They further show that DNP-enhanced
      solid-state NMR fills the gap for challenging membrane proteins between
      functional studies and X-ray-based structure analysis, which is required for
      resolving molecular mechanisms. 

PMID- 26216997
TI  - Requirement of Fra proteins for communication channels between cells in the
      filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120.
AB  - The filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120
      differentiates specialized cells, heterocysts, that fix atmospheric nitrogen and
      transfer the fixed nitrogen to adjacent vegetative cells. Reciprocally,
      vegetative cells transfer fixed carbon to heterocysts. Several routes have been
      described for metabolite exchange within the filament, one of which involves
      communicating channels that penetrate the septum between adjacent cells. Several
      fra gene mutants were isolated 25 y ago on the basis of their phenotypes:
      inability to fix nitrogen and fragmentation of filaments upon transfer from N+ to
      N- media. Cryopreservation combined with electron tomography were used to
      investigate the role of three fra gene products in channel formation. FraC and
      FraG are clearly involved in channel formation, whereas FraD has a minor part.
      Additionally, FraG was located close to the cytoplasmic membrane and in the
      heterocyst neck, using immunogold labeling with antibody raised to the N-terminal
      domain of the FraG protein. 

PMID- 26216998
TI  - ANO1 plays a critical role in prostatic hyperplasia.

PMID- 26216999
TI  - Two transcription pause elements underlie a sigma70-dependent pause cycle.
AB  - The movement of RNA polymerase (RNAP) during transcription elongation is
      modulated by DNA-encoded elements that cause the elongation complex to pause. One
      of the best-characterized pause sequences is a binding site for the sigma(70)
      initiation factor that induces pausing at a site near lambdoid phage late-gene
      promoters. An essential component of this sigma(70)-dependent pause is the
      elemental pause site (EPS), a sequence that itself induces transcription pausing
      throughout the Escherichia coli genome and underlies other complex regulatory
      pause elements, such as the ops and his operon pauses. Here, we identify and
      provide a detailed kinetic analysis of a transcription cycle analogous to
      abortive cycling that underlies the sigma(70)-dependent pause. We show that, in
      sigma(70)-dependent pausing, the elemental pause acts primarily to modulate the
      rate at which complexes attempt to disengage the sigma(70):DNA interaction. Our
      findings establish the sigma(70)-dependent pause-encoding region as a
      multipartite element in which several pause-inducing components make distinct
      mechanistic contributions to the induction and maintenance of a regulatory
      transcription pause. 

PMID- 26217000
TI  - Conversion of lowland tropical forests to tree cash crop plantations loses up to
      one-half of stored soil organic carbon.
AB  - Tropical deforestation for the establishment of tree cash crop plantations causes
      significant alterations to soil organic carbon (SOC) dynamics. Despite this
      recognition, the current Intergovernmental Panel on Climate Change (IPCC) tier 1
      method has a SOC change factor of 1 (no SOC loss) for conversion of forests to
      perennial tree crops, because of scarcity of SOC data. In this pantropic study,
      conducted in active deforestation regions of Indonesia, Cameroon, and Peru, we
      quantified the impact of forest conversion to oil palm (Elaeis guineensis),
      rubber (Hevea brasiliensis), and cacao (Theobroma cacao) agroforestry plantations
      on SOC stocks within 3-m depth in deeply weathered mineral soils. We also
      investigated the underlying biophysical controls regulating SOC stock changes.
      Using a space-for-time substitution approach, we compared SOC stocks from paired
      forests (n = 32) and adjacent plantations (n = 54). Our study showed that
      deforestation for tree plantations decreased SOC stocks by up to 50%. The key
      variable that predicted SOC changes across plantations was the amount of SOC
      present in the forest before conversion--the higher the initial SOC, the higher
      the loss. Decreases in SOC stocks were most pronounced in the topsoil, although
      older plantations showed considerable SOC losses below 1-m depth. Our results
      suggest that (i) the IPCC tier 1 method should be revised from its current SOC
      change factor of 1 to 0.6 +/- 0.1 for oil palm and cacao agroforestry plantations
      and 0.8 +/- 0.3 for rubber plantations in the humid tropics; and (ii) land use
      management policies should protect natural forests on carbon-rich mineral soils
      to minimize SOC losses.

PMID- 26217002
TI  - Transitional cell carcinoma arising in a tailgut cyst.
AB  - Malignant transformation in tailgut cysts (TGCs) is extremely rare, with no
      reports of transitional cell carcinoma arising in them in the UK literature.
      Here, we discuss a case of a patient with a malignant TGC encapsulating the
      rectum. This case report highlights the pathological and diagnostic
      considerations and discusses its management. 

PMID- 26217001
TI  - Mitochondrial calcium overload is a key determinant in heart failure.
AB  - Calcium (Ca2+) released from the sarcoplasmic reticulum (SR) is crucial for
      excitation-contraction (E-C) coupling. Mitochondria, the major source of energy,
      in the form of ATP, required for cardiac contractility, are closely
      interconnected with the SR, and Ca2+ is essential for optimal function of these
      organelles. However, Ca2+ accumulation can impair mitochondrial function, leading
      to reduced ATP production and increased release of reactive oxygen species (ROS).
      Oxidative stress contributes to heart failure (HF), but whether mitochondrial
      Ca2+ plays a mechanistic role in HF remains unresolved. Here, we show for the
      first time, to our knowledge, that diastolic SR Ca2+ leak causes mitochondrial
      Ca2+ overload and dysfunction in a murine model of postmyocardial infarction HF.
      There are two forms of Ca2+ release channels on cardiac SR: type 2 ryanodine
      receptors (RyR2s) and type 2 inositol 1,4,5-trisphosphate receptors (IP3R2s).
      Using murine models harboring RyR2 mutations that either cause or inhibit SR Ca2+
      leak, we found that leaky RyR2 channels result in mitochondrial Ca2+ overload,
      dysmorphology, and malfunction. In contrast, cardiac-specific deletion of IP3R2
      had no major effect on mitochondrial fitness in HF. Moreover, genetic enhancement
      of mitochondrial antioxidant activity improved mitochondrial function and reduced
      posttranslational modifications of RyR2 macromolecular complex. Our data
      demonstrate that leaky RyR2, but not IP3R2, channels cause mitochondrial Ca2+
      overload and dysfunction in HF.

PMID- 26217003
TI  - Appendiceal diverticulitis shortly after a performed laparoscopic sigma
      resection.
AB  - Diverticulosis of the vermiform appendix is rare and usually asymptomatic or
      associated with mild, chronic or intermittent abdominal pain. A 52-year-old
      patient was admitted to our department due to lower abdominal pain. Assuming the
      second episode of diverticulitis of the sigmoid, a computed tomography (CT) was
      performed, and complicated sigmoid diverticulitis and an accentuated appendix
      without inflammatory signs were diagnosed. Laparoscopic sigmoid resection was
      performed with an intraoperative macroscopic inconspicuous appendix. Two months
      later, right-sided abdominal pain returned. CT scan showed increasing signs of
      thickened appendix. Because of a gallbladder polyp, a combined laparoscopic
      appendectomy and cholecystectomy with one additional laparoscopic access was
      performed. Pathology detected a small diverticulum of the appendix and a small
      tubular adenoma with low-grade intraepithelial neoplasia in the gallbladder.
      Although diverticulitis of the appendix is very rare, it should be considered in
      patients with right lower abdominal pain, and appendectomy should be performed
      even in macroscopic unsuspicious cases. 

PMID- 26217006
TI  - Correction.

PMID- 26217005
TI  - Correction.

PMID- 26217007
TI  - Correction.

PMID- 26217008
TI  - Correction.

PMID- 26217009
TI  - Unexpected nicotine in Do-it-Yourself electronic cigarette flavourings.

PMID- 26217010
TI  - Structures and Functions of the Multiple KOW Domains of Transcription Elongation
      Factor Spt5.
AB  - The eukaryotic Spt4-Spt5 heterodimer forms a higher-order complex with RNA
      polymerase II (and I) to regulate transcription elongation. Extensive genetic and
      functional data have revealed diverse roles of Spt4-Spt5 in coupling elongation
      with chromatin modification and RNA-processing pathways. A mechanistic
      understanding of the diverse functions of Spt4-Spt5 is hampered by challenges in
      resolving the distribution of functions among its structural domains, including
      the five KOW domains in Spt5, and a lack of their high-resolution structures. We
      present high-resolution crystallographic results demonstrating that distinct
      structures are formed by the first through third KOW domains (KOW1-Linker1 [K1L1]
      and KOW2-KOW3) of Saccharomyces cerevisiae Spt5. The structure reveals that K1L1
      displays a positively charged patch (PCP) on its surface, which binds nucleic
      acids in vitro, as shown in biochemical assays, and is important for in vivo
      function, as shown in growth assays. Furthermore, assays in yeast have shown that
      the PCP has a function that partially overlaps that of Spt4. Synthesis of our
      results with previous evidence suggests a model in which Spt4 and the K1L1 domain
      of Spt5 form functionally overlapping interactions with nucleic acids upstream of
      the transcription bubble, and this mechanism may confer robustness on processes
      associated with transcription elongation. 

PMID- 26217011
TI  - Distinct Intracellular Domain Substrate Modifications Selectively Regulate
      Ectodomain Cleavage of NRG1 or CD44.
AB  - Ectodomain cleavage by A-disintegrin and -metalloproteases (ADAMs) releases many
      important biologically active substrates and is therefore tightly controlled.
      Part of the regulation occurs on the level of the enzymes and affects their cell
      surface abundance and catalytic activity. ADAM-dependent proteolysis occurs
      outside the plasma membrane but is mostly controlled by intracellular signals.
      However, the intracellular domains (ICDs) of ADAM10 and -17 can be removed
      without consequences for induced cleavage, and so far it is unclear how
      intracellular signals address cleavage. We therefore explored whether substrates
      themselves could be chosen for proteolysis via ICD modification. We report here
      that CD44 (ADAM10 substrate), a receptor tyrosine kinase (RTK) coreceptor
      required for cellular migration, and pro-NRG1 (ADAM17 substrate), which releases
      the epidermal growth factor (EGF) ligand neuregulin required for axonal outgrowth
      and myelination, are indeed posttranslationally modified at their ICDs.
      Tetradecanoyl phorbol acetate (TPA)-induced CD44 cleavage requires
      dephosphorylation of ICD serine 291, while induced neuregulin release depends on
      the phosphorylation of several NRG1-ICD serines, in part mediated by protein
      kinase Cdelta (PKCdelta). Downregulation of PKCdelta inhibits neuregulin release
      and reduces ex vivo neurite outgrowth and myelination of trigeminal ganglion
      explants. Our results suggest that specific selection among numerous substrates
      of a given ADAM is determined by ICD modification of the substrate. 

PMID- 26217012
TI  - Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA.
AB  - Loss of the RNA-binding protein Bicaudal-C (Bicc1) provokes renal and pancreatic
      cysts as well as ectopic Wnt/beta-catenin signaling during visceral left-right
      patterning. Renal cysts are linked to defective silencing of Bicc1 target mRNAs,
      including adenylate cyclase 6 (AC6). RNA binding of Bicc1 is mediated by N
      terminal KH domains, whereas a C-terminal sterile alpha motif (SAM) self
      polymerizes in vitro and localizes Bicc1 in cytoplasmic foci in vivo. To assess a
      role for multimerization in silencing, we conducted structure modeling and then
      mutated the SAM domain residues which in this model were predicted to polymerize
      Bicc1 in a left-handed helix. We show that a SAM-SAM interface concentrates Bicc1
      in cytoplasmic clusters to specifically localize and silence bound mRNA. In
      addition, defective polymerization decreases Bicc1 stability and thus indirectly
      attenuates inhibition of Dishevelled 2 in the Wnt/beta-catenin pathway.
      Importantly, aberrant C-terminal extension of the SAM domain in bpk mutant Bicc1
      phenocopied these defects. We conclude that polymerization is a novel disease
      relevant mechanism both to stabilize Bicc1 and to present associated mRNAs in
      specific silencing platforms. 

PMID- 26217013
TI  - C/EBPbeta and Nuclear Factor of Activated T Cells Differentially Regulate Adamts
      1 Induction by Stimuli Associated with Vascular Remodeling.
AB  - Emerging evidence indicates that the metalloproteinase Adamts-1 plays a
      significant role in the pathophysiology of vessel remodeling, but little is known
      about the signaling pathways that control Adamts-1 expression. We show that
      vascular endothelial growth factor (VEGF), angiotensin-II, interleukin-1beta, and
      tumor necrosis factor alpha, stimuli implicated in pathological vascular
      remodeling, increase Adamts-1 expression in endothelial and vascular smooth
      muscle cells. Analysis of the intracellular signaling pathways implicated in this
      process revealed that VEGF and angiotensin-II upregulate Adamts-1 expression via
      activation of differential signaling pathways that ultimately promote functional
      binding of the NFAT or C/EBPbeta transcription factors, respectively, to the
      Adamts-1 promoter. Infusion of mice with angiotensin-II triggered phosphorylation
      and nuclear translocation of C/EBPbeta proteins in aortic cells concomitantly
      with an increase in the expression of Adamts-1, further underscoring the
      importance of C/EBPbeta signaling in angiotensin-II-induced upregulation of
      Adamts-1. Similarly, VEGF promoted NFAT activation and subsequent Adamts-1
      induction in aortic wall in a calcineurin-dependent manner. Our results
      demonstrate that Adamts-1 upregulation by inducers of pathological vascular
      remodeling is mediated by specific signal transduction pathways involving NFAT or
      C/EBPbeta transcription factors. Targeting of these pathways may prove useful in
      the treatment of vascular disease. 

PMID- 26217014
TI  - Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for
      Nonoverlapping Functions of Rtf1 and the Paf1 Complex.
AB  - Restores TBP function 1 (Rtf1) is generally considered to be a subunit of the
      Paf1 complex (PAF1C), a multifunctional protein complex involved in histone
      modification and transcriptional or posttranscriptional regulation. Rtf1,
      however, is not stably associated with the PAF1C in most species except
      Saccharomyces cerevisiae, and its biochemical functions are not well understood.
      Here, we show that human Rtf1 is a transcription elongation factor that may
      function independently of the PAF1C. Rtf1 requires "Rtf1 coactivator" activity,
      which is most likely unrelated to the PAF1C or DSIF, for transcriptional
      activation in vitro. A mutational study revealed that the Plus3 domain of human
      Rtf1 is critical for its coactivator-dependent function. Transcriptome sequencing
      (RNA-seq) and chromatin immunoprecipitation studies in HeLa cells showed that
      Rtf1 and the PAF1C play distinct roles in regulating the expression of a subset
      of genes. Moreover, contrary to the finding in S. cerevisiae, the PAF1C was
      apparently recruited to the genes examined in an Rtf1-independent manner. The
      present study establishes a role for human Rtf1 as a transcription elongation
      factor and highlights the similarities and differences between the S. cerevisiae
      and human Rtf1 proteins. 

PMID- 26217015
TI  - Sequestration of mRNAs Modulates the Timing of Translation during Meiosis in
      Budding Yeast.
AB  - Starvation of diploid cells of the budding yeast Saccharomyces cerevisiae induces
      them to enter meiosis and differentiate into haploid spores. During meiosis, the
      precise timing of gene expression is controlled at the level of transcription,
      and also translation. If cells are returned to rich medium after they have
      committed to meiosis, the transcript levels of most meiotically upregulated genes
      decrease rapidly. However, for a subset of transcripts whose translation is
      delayed until the end of meiosis II, termed protected transcripts, the transcript
      levels remain stable even after nutrients are reintroduced. The Ime2-Rim4
      regulatory circuit controls both the delayed translation and the stability of
      protected transcripts. These protected mRNAs localize in discrete foci, which are
      not seen for transcripts of genes with different translational timing and are
      regulated by Ime2. These results suggest that Ime2 and Rim4 broadly regulate
      translational delay but that additional factors, such as mRNA localization,
      modulate this delay to tune the timing of gene expression to developmental
      transitions during sporulation. 

PMID- 26217016
TI  - CRB3A Controls the Morphology and Cohesion of Cancer Cells through
      Ehm2/p114RhoGEF-Dependent Signaling.
AB  - The transmembrane protein CRB3A controls epithelial cell polarization.
      Elucidating the molecular mechanisms of CRB3A function is essential as this
      protein prevents the epithelial-to-mesenchymal transition (EMT), which
      contributes to tumor progression. To investigate the functional impact of altered
      CRB3A expression in cancer cells, we expressed CRB3A in HeLa cells, which are
      devoid of endogenous CRB3A. While control HeLa cells display a patchy F-actin
      distribution, CRB3A-expressing cells form a circumferential actomyosin belt. This
      reorganization of the cytoskeleton is accompanied by a transition from an ameboid
      cell shape to an epithelial-cell-like morphology. In addition, CRB3A increases
      the cohesion of HeLa cells. To perform these functions, CRB3A recruits p114RhoGEF
      and its activator Ehm2 to the cell periphery using both functional motifs of its
      cytoplasmic tail and increases RhoA activation levels. ROCK1 and ROCK2 (ROCK1/2),
      which are critical effectors of RhoA, are also essential to modulate the
      cytoskeleton and cell shape downstream of CRB3A. Overall, our study highlights
      novel roles for CRB3A and deciphers the signaling pathway conferring to CRB3A the
      ability to fulfill these functions. Thereby, our data will facilitate further
      investigation of CRB3A functions and increase our understanding of the cellular
      defects associated with the loss of CRB3A expression in cancer cells. 

PMID- 26217017
TI  - A Pro-Nerve Growth Factor (proNGF) and NGF Binding Protein, alpha2-Macroglobulin,
      Differentially Regulates p75 and TrkA Receptors and Is Relevant to
      Neurodegeneration Ex Vivo and In Vivo.
AB  - Nerve growth factor (NGF) is generated from a precursor, proNGF, that is
      proteolytically processed. NGF preferentially binds a trophic tyrosine kinase
      receptor, TrkA, while proNGF binds a neurotrophin receptor (NTR), p75(NTR), that
      can have neurotoxic activity. Previously, we along with others showed that the
      soluble protein alpha2-macroglobulin (alpha2M) is neurotoxic. Toxicity is due in
      part to alpha2M binding to NGF and inhibiting trophic activity, presumably by
      preventing NGF binding to TrkA. However, the mechanisms remained unclear. Here,
      we show ex vivo and in vivo three mechanisms for alpha2M neurotoxicity. First,
      unexpectedly the alpha2M-NGF complexes do bind TrkA receptors but do not induce
      TrkA dimerization or activation, resulting in deficient trophic support. Second,
      alpha2M makes stable complexes with proNGF, conveying resistance to proteolysis
      that results in more proNGF and less NGF. Third, alpha2M-proNGF complexes bind
      p75(NTR) and are more potent agonists than free proNGF, inducing tumor necrosis
      factor alpha (TNF-alpha) production. Hence, alpha2M regulates proNGF/p75(NTR)
      positively and mature NGF/TrkA negatively, causing neuronal death ex vivo. These
      three mechanisms are operative in vivo, and alpha2M causes neurodegeneration in a
      p75(NTR)- and proNGF-dependent manner. alpha2M could be exploited as a
      therapeutic target, or as a modifier of neurotrophin signals. 

PMID- 26217018
TI  - Peptide-Centric Proteome Analysis: An Alternative Strategy for the Analysis of
      Tandem Mass Spectrometry Data.
AB  - In mass spectrometry-based bottom-up proteomics, data-independent acquisition is
      an emerging technique because of its comprehensive and unbiased sampling of
      precursor ions. However, current data-independent acquisition methods use wide
      precursor isolation windows, resulting in cofragmentation and complex mixture
      spectra. Thus, conventional database searching tools that identify peptides by
      interpreting individual tandem MS spectra are inherently limited in analyzing
      data-independent acquisition data. Here we discuss an alternative approach,
      peptide-centric analysis, which tests directly for the presence and absence of
      query peptides. We discuss how peptide-centric analysis resolves some limitations
      of traditional spectrum-centric analysis, and we outline the unique
      characteristics of peptide-centric analysis in general.

PMID- 26217019
TI  - Mechanistic Dissection of PARP1 Trapping and the Impact on In Vivo Tolerability
      and Efficacy of PARP Inhibitors.
AB  - Poly(ADP-ribose) polymerases (PARP1, -2, and -3) play important roles in DNA
      damage repair. As such, a number of PARP inhibitors are undergoing clinical
      development as anticancer therapies, particularly in tumors with DNA repair
      deficits and in combination with DNA-damaging agents. Preclinical evidence
      indicates that PARP inhibitors potentiate the cytotoxicity of DNA alkylating
      agents. It has been proposed that a major mechanism underlying this activity is
      the allosteric trapping of PARP1 at DNA single-strand breaks during base excision
      repair; however, direct evidence of allostery has not been reported. Here the
      data reveal that veliparib, olaparib, niraparib, and talazoparib (BMN-673)
      potentiate the cytotoxicity of alkylating agents. Consistent with this, all four
      drugs possess PARP1 trapping activity. Using biochemical and cellular approaches,
      we directly probe the trapping mechanism for an allosteric component. These
      studies indicate that trapping is due to catalytic inhibition and not allostery.
      The potency of PARP inhibitors with respect to trapping and catalytic inhibition
      is linearly correlated in biochemical systems but is nonlinear in cells. High
      content imaging of gammaH2Ax levels suggests that this is attributable to
      differential potentiation of DNA damage in cells. Trapping potency is inversely
      correlated with tolerability when PARP inhibitors are combined with temozolomide
      in mouse xenograft studies. As a result, PARP inhibitors with dramatically
      different trapping potencies elicit comparable in vivo efficacy at maximum
      tolerated doses. Finally, the impact of trapping on tolerability and efficacy is
      likely to be context specific. IMPLICATIONS: Understanding the context-specific
      relationships of trapping and catalytic inhibition with both tolerability and
      efficacy will aid in determining the suitability of a PARP inhibitor for
      inclusion in a particular clinical regimen.

PMID- 26217020
TI  - Proposed bursa of Fabricius weight to body weight ratio standard in commercial
      broilers.
AB  - Several causes may induce change and atrophy in the bursa of Fabricius (BF).
      Databases on BF standards are available from published studies, however, updated
      references are needed to adjust the BF standards to present changes in highly
      specialized broiler genetic lines. The aim of this study was to evaluate BF
      related measurements (weight and dimensions) under controlled conditions that
      would mimic field situations. Chickens were kept in isolation, thus avoiding
      exposure to disease agents by vaccination or field infections. This study was
      conducted using male Cobb 500 commercial broilers from the same hatch and source.
      Absence of disease was confirmed throughout the study. Despite the presence of
      individual variations, a minimum bursa-to-body weight ratio standard of 0.11 is
      proposed in broilers from 7 to 42 days of age. 

PMID- 26217021
TI  - Incidence of ascites syndrome and related hematological response in short-term
      feed-restricted broilers raised at low ambient temperature.
AB  - Ascites is a major cause of mortality and morbidity in modern broiler production.
      Reduction of early growth, followed by compensatory gain, seems a practical and
      viable method to minimize losses caused by ascites. An experiment was conducted
      to determine if early feed restriction can reduce the incidence of ascites in
      broilers exposed to cool temperatures. Ross 308 cockerels (N=180) were assigned
      to 5 diet treatments and 2 temperature regimes, with 3 replicate pens of 6 birds
      per treatment and temperature. A standard grower diet was diluted by adding rice
      hulls at 0, 15, 30, 45, and 60% by weight from 7 to 14 d of age. On d 21 through
      42, the temperature was maintained at 20 to 25 degrees C (thermoneutral), or at
      11 to 15 degrees C (cool). Broilers exposed to cool temperatures developed higher
      right ventricle (RV) to total ventricle (TV) and RV to BW ratios, increased
      plasma triiodothyronine (T3) and thyroxine (T4) concentrations, and elevated
      blood values for hemoglobin concentration, mean cell volume, and hematocrit
      (P<0.05) but did not develop clinical ascites. Diluting the feed with rice hulls
      from d 7 to 14 resulted in proportional reductions in BW by d 14 (P<0.001) that
      tended to persist through d 28 (P=0.005), after which compensatory growth
      eliminated all differences in BW between diet treatment groups by d 35 (P=0.099)
      and d 42 (P>0.1). Exposure to cool temperatures increased key indices of ascites
      susceptibility, and these preascitic changes were partially prevented by diluting
      the feed to reduce growth performance.

PMID- 26217023
TI  - Controlling Aspergillus flavus and Aspergillus parasiticus growth and aflatoxin
      production in poultry feed using carvacrol and trans-cinnamaldehyde.
AB  - Aflatoxins (AF) are toxic metabolites primarily produced by molds, Aspergillus
      flavus and Aspergillus parasiticus. Contamination of poultry feed with AF is a
      major concern to the poultry industry due to severe economic losses stemming from
      poor performance, reduced egg production, and diminished egg hatchability. This
      study investigated the inhibitory effect of 2 generally regarded as safe (GRAS),
      natural plant compounds, namely carvacrol (CR) and trans-cinnamaldehyde (TC), on
      A. flavus and A. parasiticus growth and AF production in potato dextrose broth
      (PDB) and in poultry feed. In broth culture, PDB supplemented with CR (0%, 0.02%,
      0.04% and 0.08%) or TC (0%, 0.005%, 0.01% and 0.02%) was inoculated with A.
      flavus or A. parasiticus (6 log CFU/mL), and mold counts and AF production were
      determined on days 0, 1, 3, and 5. Similarly, 200 g portions of poultry feed
      supplemented with CR or TC (0%, 0.4%, 0.8%, and 1.0%) were inoculated with each
      mold, and their counts and AF concentrations in the feed were determined at 0, 1,
      2, 3, 4, 8, and 12 weeks of storage. Moreover, the effect of CR and TC on the
      expression of AF synthesis genes in A. flavus and A. parasiticus (aflC, nor1,
      norA, and ver1) was determined using real-time quantitative PCR (RT-qPCR). All
      experiments had duplicate samples and were replicated 3 times. Results indicated
      that CR and TC reduced A. flavus and A. parasiticus growth and AF production in
      broth culture and chicken feed (P<0.05). All tested concentrations of CR and TC
      decreased AF production in broth culture and chicken feed by at least 60% when
      compared to controls (P<0.05). In addition, CR and TC down-regulated the
      expression of major genes associated with AF synthesis in the molds (P<0.05).
      Results suggest the potential use of CR and TC as feed additives to control AF
      contamination in poultry feed.

PMID- 26217024
TI  - An Incomplete Story Told by a Single Number.

PMID- 26217022
TI  - Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation.
AB  - Traditionally, native Australian aborigines have used emu oil for the treatment
      of inflammation and to accelerate wound healing. Studies on mice suggest that
      topically applied emu oil may have anti-inflammatory properties and may promote
      wound healing. We investigated the effects of ratite oils (6 emu, 3 ostrich, 1
      rhea) on immortalized human keratinocytes (HaCaT cells) in vitro by culturing the
      cells in media with oil concentrations of 0%, 0.5%, and 1.0%. Peking duck, tea
      tree, and olive oils were used as comparative controls. The same oils at 0.5%
      concentration were evaluated for their influence on peripheral blood mononuclear
      cell (PBMC) survival over 48 hr and their ability to inhibit IFNgamma production
      in PBMCs activated by phytohemagglutinin (PHA) in ELISpot assays. Compared to no
      oil control, significantly shorter population doubling time durations were
      observed for HaCaT cells cultured in emu oil (1.51*faster), ostrich oil
      (1.46*faster), and rhea oil (1.64*faster). Tea tree oil demonstrated significant
      antiproliferative activity and olive oil significantly prolonged (1.35*slower)
      cell population doubling time. In contrast, almost all oils, particularly tea
      tree oil, significantly reduced PBMC viability. Different oils had different
      levels of inhibitory effect on IFNgamma production with individual emu, ostrich,
      rhea, and duck oil samples conferring full inhibition. This preliminary
      investigation suggests that emu oil might promote wound healing by accelerating
      the growth rate of keratinocytes. Combined with anti-inflammatory properties,
      ratite oil may serve as a useful component in bandages and ointments for the
      treatment of wounds and inflammatory skin conditions.

PMID- 26217025
TI  - Impact of response criteria (tibia ash weight vs. percent) on phytase relative
      non phytate phosphorus equivalance.
AB  - The current study was conducted to evaluate the impacts of using tibia ash
      percentage or ash weight as the response criteria on estimated phytase relative
      equivalence. Straight run broilers were fed treatment (Trt) diets from 7 to 21 d
      age (6 birds/pen, 8 pens/Trt). The corn-soy based Trt were formulated to contain
      0.80% Ca and 4 non-phytate phosphorus (nPP) concentrations (0.20, 0.27, 0.34, and
      0.40%). Monocalcium phosphate was the inorganic phosphate source added to achieve
      4 different dietary nPP concentrations and against which the nPP relative
      equivalence of phytase was determined. A 6-phytase (Danisco Animal Nutrition,
      DuPont Industrial Biosciences, Marlborough, UK) was added at 500 or 1,000 phytase
      unit ( FTU: )/kg to the 0.20% nPP diet resulting 6 total Trts. Tibia ash was
      determined at 21 d age. Phytase fed at 500 or 1,000 FTU/kg increased tibia ash
      weight and ash percentage compared to that of birds fed 0.20% nPP diet without
      phytase (P<0.05). Graded nPP were log transformed and regressed against tibia ash
      (weight and percentage) to calculate phytase nPP relative equivalence. The R2
      obtained from pen value regressions were 0.81 and 0.84, for tibia ash weight and
      percentage, respectively. Ash percentage from birds fed 500 and 1,000 FTU
      phytase/kg fell within the range obtained with the MCP additions. Ash weight (842
      mg/tibia) from birds fed 1,000 FTU phytase/kg exceeded (P<0.05) maximum weight
      (773 mg/tibia) measured in birds fed the greatest nPP Trt (0.40%), thus the nPP
      relative equivalence was only calculated in birds fed 500 FTU phytase/kg Trt. The
      nPP relative equivalence in birds fed 500 FTU phytase/kg were 0.117 and 0.168%
      based on ash percentage and weight, respectively (P<0.05). The nPP relative
      equivalence in birds fed 1,000 FTU phytase/kg was 0.166% for ash percentage.
      Results suggested that ash weight better reflects the amount of bone
      mineralization as compared to ash percentage and using ash percentage may lead to
      an underestimation of phytase efficacy.

PMID- 26217026
TI  - Effects of egg storage on hatchability, chick quality, performance and
      immunocompetence parameters of broiler chickens.
AB  - Pre-incubation egg storage is a necessity for the poultry industry. This study
      evaluated the effects of pre-incubation storage length of broiler eggs on
      hatchability, 1-day-old chick quality, subsequent performance, and
      immunocompetence. To this end, a total of 360 hatching eggs were stored for 4,
      12, or 16 d prior to incubation. Hatchability and chick quality were assessed at
      hatch, and growth performance and immunocompetence parameters were assessed
      during a 35 d rearing period. Hatchability of set and fertile eggs, and embryonic
      mortality, were not affected by egg storage. On the contrary, 1-day-old chick BW
      and length were linearly negatively correlated with egg storage length (P
      linear<0.05). Nevertheless, BW corrected for egg weight prior to setting was
      unaffected, and corrected chick length was positively affected by storage length.
      One-day-old chick Tona score, navel quality, and post-hatch growth performance
      (BW at 7 and 35 d, cumulative feed intake, and feed conversion ratio at 35 d)
      were unaffected by egg storage (P, P-linear>0.05). Lymphoid organ weights at 2
      and 35 d, the titre of maternal anti-NDV antibodies, most of the thymocyte
      subpopulations defined by CD3, CD4, and CD8 cell surface expression in the thymus
      of 2-d-old chicks, cellular responses to the PHA skin test, humoral responses to
      primary SRBC, and NDV immunizations were also not influenced by length of storage
      (P, P-linear>0.05). On the contrary, the length of egg storage was found to
      negatively influence the abundance of CD3+CD4-CD8- thymocytes that represent the
      majority of gammadelta-T cells in the thymus of 2-day-old chicks, as well as the
      humoral response to booster NDV immunization of the birds. In brief, pre
      incubation storage of broiler hatching eggs for up to 16 d did not affect most
      developmental and growth parameters investigated, except for BW and length at
      hatch. Egg storage was found to suppress some aspects of the immunocompetence of
      the birds, particularly aspects of acquired immunity.

PMID- 26217027
TI  - An assessment of the effectiveness of four in-house treatments to reduce the
      bacterial levels in poultry litter.
AB  - Although the use of quicklime (CaO) and tarping are common handling practices
      aimed at the reuse of litter in the Brazilian poultry industry, few scientific
      studies have proven the effectiveness of these methods in reducing the pathogenic
      microbial load during fallowing. The objective of this study was to evaluate the
      following litter treatments: T1 no treatment (control), T2 quicklime (300 g m(
      2)), T3 tarping, T4 tarping+quicklime (300 g m(-2)). The litter samples were
      collected on day zero and on the sixth and twelfth days after the start of
      fallowing. The use of quicklime alone or quicklime+tarping was more effective
      (P<0.05) in reducing bacteria when compared to litter tarping. Except for the
      control group, all treatments resulted in a more than 84% reduction in the count
      of colony-forming units (CFUs) at the end of fallowing. It is concluded that the
      use of quicklime alone in practical terms is the most indicated treatment for the
      reduction of the bacterial load of poultry litter.

PMID- 26217028
TI  - The effects of high-pressure treatments on Campylobacter jejuni in ground poultry
      products containing polyphosphate additives.
AB  - Marinades containing polyphosphates have been previously implicated in the
      enhanced survival of Campylobacter spp. in poultry product exudates. The enhanced
      Campylobacter survival has been attributed primarily to the ability of some
      polyphosphates to change the pH of the exudate to one more amenable to
      Campylobacter. In this study a ground poultry product contaminated with a 6
      strain Campylobacter jejuni cocktail was utilized to determine if the efficiency
      of high-hydrostatic-pressure treatments was negatively impacted by the presence
      of commonly utilized polyphosphates. Two polyphosphates, hexametaphosphate and
      sodium tripolyphosphate, used at 2 concentrations, 0.25 and 0.5%, failed to
      demonstrate any significant negative effects on the efficiency of inactivation of
      C. jejuni by high-pressure treatment. However, storage at 4 degrees C of the
      ground poultry samples containing C. jejuni after high-pressure treatment
      appeared to provide a synergistic effect on Campylobacter inactivation. High
      pressure treatment in conjunction with 7 d of storage at 4 degrees C resulted in
      a mean reduction in C. jejuni survival that was larger than the sum of the
      individual reductions caused by high pressure or 4 degrees C storage when applied
      separately. 

PMID- 26217029
TI  - Effect of Scrophularia striata and Ferulago angulata, as alternatives to
      virginiamycin, on growth performance, intestinal microbial population, immune
      response, and blood constituents of broiler chickens.
AB  - An experiment was conducted to investigate the comparative effect of Scrophularia
      striata, Ferulago angulata, and virginiamycin (VM) on performance, intestinal
      microbial population, immune response, and blood constituents of broilers. A
      total of 300 Ross 308 male broiler chickens were randomly assigned to 5
      treatments, with 5 replicates/treatment (10 chickens/pen). Birds were fed either
      a corn-soybean meal basal diet (control) or the basal diet supplemented with 200
      mg/kg VM; 4 g/kg S. striata (SS1); 8 g/kg S. striata (SS2); 4 g/kg F. angulata
      (FA1); or 8 g/kg F. angulata (FA2). After 6 wk, the BW, ADG, and feed-to-gain
      ratio (F:G) of the VM, SS1, and FA1 groups were better (P<0.01) compared with the
      control group. At 42 d, cecal lactobacillus counts were higher (P=0.032) in SS2
      and FA2 groups compared with the control and VM groups. In addition, broilers fed
      any of the diets exhibited lower coliform counts (P<0.05) in the ileum and ceca
      than those fed the control diet. Total and IgG antibody titers against SRBC for
      secondary responses, relative spleen weight, and lymphocyte counts were higher
      (P<0.05) in birds fed the SS2 or FA2 diet compared with the control group.
      Moreover, feeding the SS2 or FA2 diet decreased (P<0.05) the blood
      heterophil/lymphocyte ratio and plasma triglyceride level, whereas only the SS2
      diet increased (P=0.037) the white blood cell counts compared with the control
      diet. All diets, except for the VM diet, decreased (P=0.009) the plasma
      cholesterol level compared to the control treatment. The plasma high-density
      lipoprotein cholesterol level was also increased (P=0.042) in the SS2 and FA2
      groups. In conclusion, dietary S. striata or F. angulata at a level of 4 g/kg
      diet enhanced growth performance, which was comparable to that of VM used as an
      antibiotic growth promoter. Furthermore, a high dose of both herbs (8 g/kg diet)
      could beneficially affect the intestinal health and immune status of broilers.

PMID- 26217030
TI  - Cross relationships between growth performance, growth composition and feed
      composition in broiler chickens, calculated from published data.
AB  - The study presented here used experimental data obtained from 42 articles to
      calculate the cross relationships between daily feed intake (DFI), feed
      composition (AMEn and CP), BW, daily weight gain (DG), mean age (A), and
      composition (FCG and PCG; fat and protein, respectively) of growth in broilers.
      All of the experiments selected were conducted at standard temperature and with
      ad libitum feeding. The articles in this database were published from 1980 to
      2015, and represented a total of 12,277 broilers, 57 trials, and 384 basic
      treatments. Data ranged from 3 to 66, 0.077 to 3.322, 7.10 to 15.37, and 7.3 to
      35.0 for A (d), mean BW (kg), AMEn (MJ/kg) and CP (%), respectively. Equations
      were established from regression calculations to calculate daily heat production
      as a function of BW, daily AME intake (MEI) as a function of BW, DG, FCG and PCG,
      PCG as a function of A and FCG, and FCG as a function of BW, protein efficiency
      (PE), AMEn, and CP. The combination of these equations expressing MEI, PCG, or
      FCG with equations expressing the definitions of PE, AME (from AMEn), and DFI
      (from MEI) constituted a system of 6 equations which could be used to determine
      DFI values from the values of AMEn, CP, A, BW, and DG. Using the values of AMEn,
      CP, A, BW, and DG from the database, the DFI values calculated with this system
      of equations showed a reasonable correlation with the DFI values measured
      (R2=0.880). This system of 6 equations yielded values for DFI, PE, PCG, and FCG
      that were in agreement with the classical effects produced by increased CP
      values, or by reduced fat deposition associated with genetic selection for
      leanness. This system of 6 equations might thus be considered an interesting
      framework for future nutritional modelling systems. Regressions predicting feed
      efficiency as a function of AMEn, CP, DG, and BW, or as a function of AMEn, FCG,
      DG, and BW showed R2 values of 0.767 and 0.747, respectively.

PMID- 26217031
TI  - Dietary vitamin D3 requirement of Chinese yellow-feathered broilers.
AB  - Three experiments have been conducted to investigate the effects of graded
      dietary levels of vitamin D3 ( VD3: ) on growth performance, metabolic regulation
      of calcium (CA), phosphorus (P), and bone development of Chinese yellow-feathered
      broilers during 3 growth phases: 1 to 21 d, 22 to 42 d, and 43 to 63 d. Dietary
      Ca and P in the corn-soybean-based diet were adequate. A total of 2,000 1-day
      old, 1,600 22-day-old, and 1,600 43-day- old Lingnan yellow male broilers were
      randomly assigned to 1 of 8 dietary treatments with 5 replicates per treatment
      (50 birds per replicate for 1 to 21 d, 40 birds for both 22 to 42 d and 43 to 63
      d). Dietary levels of VD3 were 100, 200, 300, 400, 500, 600, and 700 IU/kg for
      treatments 2 to 8 through the addition of VD3 to the basal mash diet which
      otherwise lacked detectable VD3. Graded doses of VD3 from 0 to 700 IU/kg in the
      diet produced linear (P<0.01) positive responses in ADG, ADFI, tibial weight, and
      breaking strength, and quadratic (P<0.01) responses in tibial length, bone
      density, ash, the levels of Ca and P in the ash , and the ratio of Ca to P. Serum
      concentrations of Ca, P, 25-hydroxycholecalciferol, osteocalcin, and calcitonin
      increased, and concentrations of fibroblast growth factor 23, Klotho protein, and
      parathyroid hormone all decreased with the increasing level of dietary VD3
      (P<0.05). Adding VD3 improved meat color a* value and decreased shear force and
      drip loss of birds at 63 d (P<0.05). Considering bone characteristics and
      composition under the conditions of this study, it was concluded that the VD3
      requirements of Chinese yellow-feathered broilers from 1 to 21 d for optimal
      tibial ash content were estimated from regression analysis to be 464 IU/kg from 1
      to 21 d, 539 IU/kg from 22 to 42 d, and 500 IU/kg from 43 to 63 d.

PMID- 26217032
TI  - Impact of coccidiosis control program and feeding plan on white striping
      prevalence and severity degree on broiler breast fillets evaluated at three
      growing ages.
AB  - This study investigated the impact of 2 coccidiosis control systems (vaccine vs
      anticoccidial) and 2 feeding plans (standard energy vs low energy content, the
      latter supplemented with threonine and enzymes in the second half of the
      production cycle) on white striping (WS) prevalence and severity in chicken
      broiler breasts at commercial slaughter age (51 d). The age of lesion onset was
      also investigated with the sacrifice of 80 chicks at 12, and 80 chicks at 25 d of
      age. Seven hundred and twenty ROSS 708 strain male chicks were divided into 4
      groups: a non-vaccinated group fed with standard diet (CONTROL); two groups
      vaccinated against coccidiosis but fed either a standard diet (VACC) or a low
      energy diet supplemented with threonine and enzymes (VACC-LE plus); and a fourth
      group fed a standard diet containing anticoccidial additive except during the
      finishing period (COX). After live performance, yields, and fillet pH were
      measured, the breasts were weighed and scored as level 0 (no WS), level 1
      (moderate WS), and level 2 (severe WS) at each of the 3 ages; data were covariate
      for slaughter weight. The results suggest an ameliorative effect of coccidiosis
      control systems when compared to the control group in terms of live weight,
      breast yield, and whole breast weight, with heavier fillets characterized by
      higher pH values. WS appeared at 25 d of age with an average prevalence of 11.5%
      and with lesions of moderate severity. There were no statistically significant
      differences due to the experimental treatment at this age. At commercial
      slaughter age, total average prevalence was 96%, with COX birds showing higher
      level 2 prevalence (77.6%). This could be related to the higher slaughter weight
      reached by the COX group (P<0.001) and the treatment effect (P<0.01) that
      probably adds to the effect of live weight. Diet had no effect on overall live
      performance of VACC-LE plus chickens, which were similar to those of the VACC
      group.

PMID- 26217033
TI  - Effects of different vaccine combinations against Mycoplasma gallisepticum on
      blood characteristics in commercial layer chickens.
AB  - Mycoplasma gallisepticum (MG) is a major and economically significant pathogen of
      avian species. When administered before lay, F-strain MG (FMG) can reduce egg
      production during lay, but the ts-11 strain of MG (ts11MG) does not exert this
      effect. Two trials were conducted to determine the effects of pre-lay
      vaccinations of ts11MG, MG-Bacterin (MGBac), or their combination, in conjunction
      with an FMG challenge overlay after peak production on the blood characteristics
      of commercial layers. In each trial, 160 mycoplasma-free Hy-Line W-36 layers were
      housed in negative-pressure biological isolation units (4 units per treatment, 10
      birds per unit) from 9 through 52 wk of age (woa). The following vaccination
      treatments were administered at 10 woa: 1) Control (no vaccinations); 2) MGBac;
      3) ts11MG; and 4) ts11MG and MGBac combination (ts11MG+MGBac). At 45 woa, half of
      the birds were challenged with a laboratory stock of high-passage FMG. Parameters
      measured in both trials were whole-blood hematocrit and serum concentrations of
      cholesterol (SCHOL), triglycerides, calcium, and total protein (STP). An
      age*treatment interaction (P=0.04) was observed for STP between 23 and 43 woa.
      The STP concentration in the ts11MG and ts11MG+MGBac groups was higher at 33 woa,
      but was lower at 43 woa, in comparison to the Control group. Also, at 38 woa, the
      STP of the ts11MG+MGBac group was higher than that of the MGBac group. Although
      use of the ts11MG vaccine alone or in combination with MGBac may influence
      circulating STP concentrations when administered before lay, it remains effective
      in protecting layers against the adverse effect of a post-peak challenge of FMG
      on egg production, as was observed in a previous companion study.

PMID- 26217034
TI  - Screening for genes involved in antibody response to sheep red blood cells in the
      chicken, Gallus gallus.
AB  - Antibody response, an important trait in both agriculture and biomedicine, plays
      a part in protecting animals from infection. Dissecting molecular basis of
      antibody response may improve artificial selection for natural disease resistance
      in livestock and poultry. A number of genetic markers associated with antibody
      response have been identified in the chicken and mouse by linkage-based
      association studies, which only define genomic regions by genetic markers but do
      not pinpoint genes for antibody response. In contrast, global expression
      profiling has been applied to define the molecular bases of a variety of
      biological traits through identification of differentially expressed genes
      (DEGs). Here, we employed Affimetrix GeneChip Chicken Genome Arrays to identify
      differentially expressed genes for antibody response to sheep red blood cells
      (SRBC) using chickens challenged with and without SRBC or chickens with high and
      low anti-SRBC titers. The DEGs include those with known (i.e., MHC class I and
      IgH genes) or unknown function in antibody response. Classification test of these
      genes suggested that the response of the chicken to intravenous injection of SRBC
      involved multiple biological processes, including response to stress or other
      different stimuli, sugar, carbohydrate or protein binding, and cell or soluble
      fraction, in addition to antibody response. This preliminary study thus provides
      an insight into molecular basis of antibody response to SRBC in the chicken. 

PMID- 26217035
TI  - c-Abl-mediated tyrosine phosphorylation of JunB is required for Adriamycin
      induced expression of p21.
AB  - The non-receptor-type tyrosine kinase c-Abl functions as a cytoplasmic signal
      transducer upon activation of cell-surface receptors. c-Abl is also involved in
      DDR (DNA-damage response), which is initiated in the nucleus, whereas its
      molecular functions in DDR are not fully understood. In the present study, we
      found that c-Abl phosphorylates JunB, a member of the AP-1 (activator protein 1)
      transcription factor family. Because JunB was suggested to be involved in DDR, we
      analysed the role of c-Abl-mediated phosphorylation of JunB in DDR. We first
      analysed phosphorylation sites of JunB and found that c-Abl majorly
      phosphorylates JunB at Tyr(173), Tyr(182) and Tyr(188). Because c-Abl promotes
      expression of the cyclin-dependent kinase inhibitor p21 upon stimulation with the
      DNA-damaging agent Adriamycin (doxorubicin), we analysed the involvement of JunB
      in Adriamycin-induced p21 expression. We found that JunB suppresses p21 induction
      through inhibition of its promoter activity. The phosphomimetic JunB, which was
      generated by glutamic acid substitutions at the phosphorylation sites, failed to
      repress p21 induction. Recruitment of JunB to the p21 promoter was promoted by
      Adriamycin stimulation and was further enhanced by co-treatment with the c-Abl
      inhibitor imatinib. The phosphomimetic glutamic acid substitutions in JunB or
      Adriamycin treatment impaired the JunB-c-Fos transcription factor complex
      formation. Taken together, these results suggest that, although JunB represses
      p21 promoter activity, c-Abl phosphorylates JunB and conversely inhibits its
      suppressive role on p21 promoter activity upon Adriamycin stimulation. Therefore
      JunB is likely to be a key target of c-Abl in expression of p21 in Adriamycin
      induced DDR. 

PMID- 26217036
TI  - Somatosensory evoked potentials aid prediction after hypoxic-ischaemic brain
      injury.
AB  - Cardiopulmonary resuscitation, basic life support and early defibrillation are
      leading to more survivors of out-of-hospital cardiac arrest reaching hospital.
      Once stabilised on an intensive care unit, it can be difficult to predict the
      neurological outcome using clinical criteria alone, particularly with modern
      management using sedation, neuromuscular blockade and hypothermia. If we are to
      prevent ongoing futile life support, it is important to try to identify the
      majority of patients who, despite best efforts, will not make a meaningful
      recovery. Somatosensory evoked potentials are widely available
      electrophysiological tests that can provide an objective biomarker of a poor
      neurological outcome and assist in predicting the prognosis.

PMID- 26217037
TI  - Patient safety incident reporting: a qualitative study of thoughts and
      perceptions of experts 15 years after 'To Err is Human'.
AB  - One of the key recommendations of the Institute of Medicine's (IOM) report, To
      Err is Human, 15 years ago was for greater attention to incident reporting in
      healthcare, analogous to the role it has played in aviation and other high-risk
      industries. With the passage of time and maturation of the patient safety field,
      we conducted semistructured interviews with 11 international patient safety
      experts with knowledge of the US healthcare and meeting at least one of the
      following criteria: (1) involved in the development of the IOM's recommendations,
      (2) responsible for the design and/or implementation of national or regional
      incident reporting systems, (3) conducted research on patient safety/incident
      reporting at a national level. Five key challenges emerged to explain why
      incident reporting has not reached its potential: poor processing of incident
      reports (triaging, analysis, recommendations), inadequate engagement of doctors,
      insufficient subsequent visible action, inadequate funding and institutional
      support of incident reporting systems and inadequate usage of evolving health
      information technology. Leading patient safety experts acknowledge the current
      challenges of incident reports. The future of incident reporting lies in targeted
      incident reporting, effective triaging and robust analysis of the incident
      reports and meaningful engagement of doctors. Incident reporting must be coupled
      with visible, sustainable action and linkage of incident reports to the
      electronic health record. If the healthcare industry wants to learn from its
      mistakes, miss or near miss events, it will need to take incident reporting as
      seriously as the health budget. 

PMID- 26217038
TI  - "Anybody on this list that you're more worried about?" Qualitative analysis
      exploring the functions of questions during end of shift handoffs.
AB  - BACKGROUND: Shift change handoffs are known to be a point of vulnerability in the
      quality, safety and outcomes of healthcare. Despite numerous efforts to improve
      handoff reliability, few interventions have produced lasting change. Although the
      opportunity to ask questions during patient handoff has been required by some
      regulatory bodies, the function of questions during handoff has been less well
      explored and understood. OBJECTIVE: To investigate questions and the functions
      they serve in nursing and medicine handoffs. RESEARCH DESIGN: Qualitative
      thematic analysis based on audio recordings of nurse-to-nurse, medical resident
      to-resident and surgical intern-to-intern handoffs. SUBJECTS: Twenty-seven nurse
      handoff dyads and 18 medical resident and surgical intern handoff dyads at one VA
      Medical Center. RESULTS: Our analysis revealed that the vast majority of
      questions were asked by the Incoming Providers. Although topics varied widely,
      the bulk of Incoming Provider questions requested information that would best
      help them understand individual patient conditions and plan accordingly. Other
      question types sought consensus on clinical reasoning or framing and alignment
      between the two professionals. CONCLUSIONS: Handoffs are a type of socially
      constructed work. Questions emerge with some frequency in virtually all handoffs
      but not in a linear or predictable way. Instead, they arise in the moment, as
      necessary, and without preplanning. A checklist cannot model this process element
      because it is a static memory aid and questions occur in a relational context
      that is emergent. Studying the different functions of questions during end of
      shift handoffs provides insights into the interface between the technical context
      in which information is transferred and the social context in which meaning is
      created.

PMID- 26217039
TI  - 'Speaking up' climate: a new domain of culture to measure and explore.

PMID- 26217040
TI  - Economic Burden of Dengue Virus Infection at the Household Level Among Residents
      of Puerto Maldonado, Peru.
AB  - Dengue virus (DENV) was reintroduced to Peru in the 1990s and has been reported
      in Puerto Maldonado (population ~65,000) in the Peruvian southern Amazon basin
      since 2000. This region also has the highest human migration rate in the country,
      mainly from areas not endemic for DENV. The objective of this study was to assess
      the proportion of household income that is diverted to costs incurred because of
      dengue illness and to compare these expenses between recent migrants (RMs) and
      long-term residents (LTRs). We administered a standardized questionnaire to
      persons diagnosed with dengue illness at Hospital Santa Rosa in Puerto Maldonado
      from December 2012 to March 2013. We compared direct and indirect medical costs
      between RMs and LTRs. A total of 80 participants completed the survey, of whom 28
      (35%) were RMs and 52 (65%) were LTRs. Each dengue illness episode cost the
      household an average of US$105 (standard deviation [SD] = 107), representing 24%
      of their monthly income. Indirect costs were the greatest expense (US$56, SD =
      87), especially lost wages. The proportion of household income diverted to dengue
      illness did not differ significantly between RM and LTR households. The study
      highlights the significant financial burden incurred by households when a family
      member suffers dengue illness.

PMID- 26217041
TI  - Cysticercosis with an Orbital Tropism in Twins.
AB  - Two fraternal twin sisters developed cysticercosis localizing to the right
      lateral orbit over the same period after a presumed common-source exposure in
      China. This case demonstrates that cysticercosis can be related to travel.
      Similar temporal and spatial occurrences of these infections suggest a genetic
      tropism of the infecting organism in these twins. 

PMID- 26217042
TI  - Modeling the Present and Future Geographic Distribution of the Lone Star Tick,
      Amblyomma americanum (Ixodida: Ixodidae), in the Continental United States.
AB  - The Lone star tick (Amblyomma americanum L.) is the primary vector for pathogens
      of significant public health importance in North America, yet relatively little
      is known about its current and potential future distribution. Building on a
      published summary of tick collection records, we used an ensemble modeling
      approach to predict the present-day and future distribution of climatically
      suitable habitat for establishment of the Lone star tick within the continental
      United States. Of the nine climatic predictor variables included in our five
      present-day models, average vapor pressure in July was by far the most important
      determinant of suitable habitat. The present-day ensemble model predicted an
      essentially contiguous distribution of suitable habitat extending to the Atlantic
      coast east of the 100th western meridian and south of the 40th northern parallel,
      but excluding a high elevation region associated with the Appalachian Mountains.
      Future ensemble predictions for 2061-2080 forecasted a stable western range
      limit, northward expansion of suitable habitat into the Upper Midwest and western
      Pennsylvania, and range contraction along portions of the Gulf coast and the
      lower Mississippi river valley. These findings are informative for raising
      awareness of A. americanum-transmitted pathogens in areas where the Lone Star
      tick has recently or may become established. 

PMID- 26217043
TI  - Macrolide Resistance in the Syphilis Spirochete, Treponema pallidum ssp.
      pallidum: Can We Also Expect Macrolide-Resistant Yaws Strains?
AB  - Treponema pallidum ssp. pallidum (TPA) causes over 10 million new cases of
      syphilis worldwide whereas T. pallidum ssp. pertenue (TPE), the causative agent
      of yaws, affects about 2.5 million people. Although penicillin remains the drug
      of choice in the treatment of syphilis, in penicillin-allergic patients,
      macrolides have been used in this indication since the 1950s. Failures of
      macrolides in syphilis treatment have been well documented in the literature and
      since 2000, there has been a dramatic increase in a number of clinical samples
      with macrolide-resistant TPA. Scarce data regarding the genetics of macrolide
      resistant mutations in TPA suggest that although macrolide-resistance mutations
      have emerged independently several times, the increase in the proportion of TPA
      strains resistant to macrolides is mainly due to the spread of resistant strains,
      especially in developed countries. The emergence of macrolide resistance in TPA
      appears to require a two-step process including either A2058G or A2059G mutation
      in one copy of the 23S rRNA gene and a subsequent gene conversion unification of
      both rRNA genes. Given the enormous genetic similarity that was recently revealed
      between TPA and TPE strains, there is a low but reasonable risk of emergence and
      spread of macrolide-resistant yaws strains following azithromycin treatment. 

PMID- 26217044
TI  - Investigating Barriers to Tuberculosis Evaluation in Uganda Using Geographic
      Information Systems.
AB  - Reducing geographic barriers to tuberculosis (TB) care is a priority in high
      burden countries where patients frequently initiate, but do not complete, the
      multi-day TB evaluation process. Using routine cross-sectional study from six
      primary-health clinics in rural Uganda from 2009 to 2012, we explored whether
      geographic barriers affect completion of TB evaluation among adults with
      unexplained chronic cough. We measured distance from home parish to health center
      and calculated individual travel time using a geographic information systems
      technique incorporating roads, land cover, and slope, and measured its
      association with completion of TB evaluation. In 264,511 patient encounters,
      4,640 adults (1.8%) had sputum smear microscopy ordered; 2,783 (60%) completed TB
      evaluation. Median travel time was 68 minutes for patients with TB examination
      ordered compared with 60 minutes without (P < 0.010). Travel time differed
      between those who did and did not complete TB evaluation at only one of six
      clinics, whereas distance to care did not differ at any of them. Neither distance
      nor travel time predicted completion of TB evaluation in rural Uganda, although
      limited detail in road and village maps restricted full implementation of these
      mapping techniques. Better data are needed on geographic barriers to access
      clinics offering TB services to improve TB diagnosis. 

PMID- 26217045
TI  - Seroprevalence and risk factors of toxocariasis in preschool children in Aragua
      state, Venezuela.
AB  - BACKGROUND: Toxocariasis is a widespread zoonotic disease caused by the nematode
      Toxocara canis. In Venezuela, the magnitude of the disease is unknown and
      seroepidemiological studies have not been previously carried out in Aragua state.
      METHODS: A cross-sectional field study was conducted in eight preschools in three
      municipalities from Aragua state in Venezuela. A total of 224 children aged
      between 1 and 6 years were studied (43.8% [98/224] male and 56.2% [126/224]
      female). Blood samples were obtained for detection of IgG antibodies against
      Toxocara spp. using ELISA. Participating families were given a questionnaire and
      children included in the study were clinically evaluated by paediatricians, and
      signs and symptoms observed were included in the questionnaires. RESULTS: Anti
      Toxocara spp. antibodies were detected in 29.0% (65/224) of children. The
      seroprevalence in the different preschools studied ranged between 4.2% and 60.6%.
      Leucocytosis and eosinophilia were also detected. Analysis of questionnaires
      indicated that boys were more at risk than girls. Younger children were also more
      at risk. Other significant risk factors were socio-economic strata (IV and V),
      inadequate improvised housing, earthen flooring indoors and outdoors and the
      presence of dogs in preschools. CONCLUSIONS: The results from this work show the
      presence of infection and a high prevalence of antibodies against Toxocara spp.
      in the studied municipalities and indicate that toxocariasis poses a serious
      health problem to preschool children in Aragua state.

PMID- 26217046
TI  - Changes in Anthropometry, Upper-Body Strength, and Nutrient Intake in
      Professional Australian Football Players During a Season.
AB  - The purpose of this study was to examine the seasonal changes in body
      composition, nutrition, and upper-body (UB) strength in professional Australian
      Football (AF) players. The prospective longitudinal study examined changes in
      anthropometry (body mass, fat-free soft-tissue mass [FFSTM], and fat mass) via
      dual-energy X-ray absorptiometry 5 times during an AF season (start preseason,
      midpreseason, start season, midseason, end season) in 45 professional AF players.
      Dietary intakes and strength (bench press and bench pull) were also assessed at
      these time points. Players were categorized as experienced (>4 y experience, n =
      23) or inexperienced (<4 y experience, n = 22). Fat mass decreased during the
      preseason but was stable through the in-season for both groups. %FFSTM was
      increased during the preseason and remained constant thereafter. UB strength
      increased during the preseason and was maintained during the in-season. Changes
      in UB FFSTM were related to changes in UB-strength performance (r = .37-.40).
      Total energy and carbohydrate intakes were similar between the experienced and
      inexperienced players during the season, but there was a greater ratio of dietary
      fat intake at the start-preseason point and an increased alcohol, reduced
      protein, and increased total energy intake at the end of the season. The
      inexperienced players consumed more fat at the start of season and less total
      protein during the season than the experienced players. Coaches should also be
      aware that it can take >1 y to develop the appropriate levels of FFSTM in young
      players and take a long-term view when developing the physical and performance
      abilities of inexperienced players. 

PMID- 26217047
TI  - The Effect of Body Mass on the 30-15 Intermittent Fitness Test in Rugby Union
      Players.
AB  - PURPOSE: To evaluate the difference in performance of the 30-15 Intermittent
      Fitness Test (30-15IFT) across 4 squads in a professional rugby union club in the
      UK and consider body mass in the interpretation of the end velocity of the 30
      15IFT (VIFT). METHODS: One hundred fourteen rugby union players completed the 30
      15IFT midseason. RESULTS: VIFT demonstrated small and possibly lower (ES = -0.33;
      4/29/67) values in the under 16s compared with the under 21s, with further
      comparisons unclear. With body mass included as a covariate, all differences were
      moderate to large and very likely to almost certainly lower in the squads with
      lower body mass, with the exception of comparisons between senior and under-21
      squads. CONCLUSIONS: The data demonstrate that there appears to be a ceiling to
      the VIFT attained in rugby union players that does not increase from under-16 to
      senior level. However, the associated increases in body mass with increased
      playing level suggest that the ability to perform high-intensity running
      increases with age, although not translating into greater VIFT due to the
      detrimental effect of body mass on change of direction. Practitioners should be
      aware that VIFT is unlikely to improve, but it needs to be monitored during
      periods where increases in body mass are evident.

PMID- 26217048
TI  - Validity of Skinfold-Based Measures for Tracking Changes in Body Composition in
      Professional Rugby League Players.
AB  - High levels of lean mass are important in collision-based sports for the
      development of strength and power, which may also assist during contact
      situations. While skinfold-based measures have been shown to be appropriate for
      cross-sectional assessments of body composition, their utility in tracking
      changes in lean mass is less clear. PURPOSE: To determine the most effective
      method of quantifying changes in lean mass in rugby league athletes. METHODS:
      Body composition of 21 professional rugby league players was assessed on 2 or 3
      occasions separated by >=6 wk, including bioelectrical impedance analysis (BIA),
      lean-mass index (LMI), and a skinfold-based prediction equation (SkF). Dual-X-ray
      absorptiometry provided a criterion measure of fat-free mass (FFM). Correlation
      coefficients (r) and standard errors of the estimate (SEE) were used as measures
      of validity for the estimates. RESULTS: All 3 practical estimates exhibited
      strong validity for cross-sectional assessments of FFM (r > .9, P < .001). The
      correlation between change scores was stronger for the LMI (r = .69, SEE 1.3 kg)
      and the SkF method (r = .66, SEE = 1.4 kg) than for BIA (r = .50, SEE = 1.6 kg).
      CONCLUSIONS: The LMI is probably as accurate in predicting changes in FFM as SkF
      and very likely to be more appropriate than BIA. The LMI offers an adequate,
      practical alternative for assessing in FFM among rugby league athletes.

PMID- 26217049
TI  - Effect of Sampling Frequency on Isometric Midthigh-Pull Kinetics.
AB  - PURPOSE: Skeletal-muscle function can be evaluated using force-times curves
      generated via the isometric midthigh pull (IMTP). Various sampling frequencies
      (500-1000 Hz) have been used for IMTP assessments; however, no research has
      investigated the influence of sampling frequency on IMTP kinetics. Therefore, the
      purpose of this study was to investigate the influence of sampling frequency on
      kinetic variables during the IMTP, including peak force, time-specific force
      values (100, 150, and 200 ms), and rate of force development (RFD) at 3 time
      bands (0-100, 0-150, 0-200 ms). METHODS: Academy rugby league players (n = 30,
      age 17.5 +/- 1.1 y, height 1.80 +/- 0.06 m, mass 85.4 +/- 10.3 kg) performed 3
      IMTP trials on a force platform sampling at 2000 Hz, which was subsequently down
      sampled to 1500, 1000, and 500 Hz for analysis. RESULTS: Intraclass correlation
      coefficients (ICC) and coefficients of variation (CV) demonstrated high within
      session reliability for all force and RFD variables across all sampling
      frequencies (ICC >= .80, CV <= 10.1%). Repeated-measures analysis of variance
      revealed no significant differences (P > .05, Cohen d <= 0.009) in kinetic
      variables between sampling frequencies. Overall, high reliability was observed
      across all sampling frequencies for all kinetic variables, with no significant
      differences (P > .05) for each kinetic variable across sampling frequencies.
      CONCLUSIONS: Practitioners and scientists may consider sampling as low as 500 Hz
      when measuring peak force, time-specific force values, and RFD at predetermined
      time bands during the IMTP for accurate and reliable data.

PMID- 26217050
TI  - Experiments on cloaking in optics, thermodynamics and mechanics.
AB  - Spatial coordinate transformations can be used to transform boundaries, material
      parameters or discrete lattices. We discuss fundamental constraints in regard to
      cloaking and review our corresponding experiments in optics, thermodynamics and
      mechanics. For example, we emphasize three-dimensional broadband visible
      frequency carpet cloaking, transient thermal cloaking, three-dimensional
      omnidirectional macroscopic broadband cloaking for diffuse light throughout the
      entire visible range, cloaking for flexural waves in thin plates and three
      dimensional elasto-static core-shell cloaking using pentamode mechanical
      metamaterials. 

PMID- 26217052
TI  - Metasurfaces for general transformations of electromagnetic fields.
AB  - In this review paper I discuss electrically thin composite layers, designed to
      perform desired operations on applied electromagnetic fields. Starting from a
      historical overview and based on a general classification of metasurfaces, I give
      an overview of possible functionalities of the most general linear metasurfaces.
      The review is concluded with a short research outlook discussion. 

PMID- 26217051
TI  - Manufacture of electrical and magnetic graded and anisotropic materials for novel
      manipulations of microwaves.
AB  - Spatial transformations (ST) provide a design framework to generate a required
      spatial distribution of electrical and magnetic properties of materials to effect
      manipulations of electromagnetic waves. To obtain the electromagnetic properties
      required by these designs, the most common materials approach has involved
      periodic arrays of metal-containing subwavelength elements. While aspects of ST
      theory have been confirmed using these structures, they are often disadvantaged
      by narrowband operation, high losses and difficulties in implementation. An all
      dielectric approach involves weaker interactions with applied fields, but may
      offer more flexibility for practical implementation. This paper investigates
      manufacturing approaches to produce composite materials that may be conveniently
      arranged spatially, according to ST-based designs. A key aim is to highlight the
      limitations and possibilities of various manufacturing approaches, to constrain
      designs to those that may be achievable. The article focuses on polymer-based
      nano- and microcomposites in which interactions with microwaves are achieved by
      loading the polymers with high-permittivity and high-permeability particles, and
      manufacturing approaches based on spray deposition, extrusion, casting and
      additive manufacture. 

PMID- 26217053
TI  - Watching surface waves in phononic crystals.
AB  - In this paper, we review results obtained by ultrafast imaging of gigahertz
      surface acoustic waves in surface phononic crystals with one- and two-dimensional
      periodicities. By use of quasi-point-source optical excitation, we show how, from
      a series of images that form a movie of the travelling waves, the dispersion
      relation of the acoustic modes, their corresponding mode patterns and the
      position and widths of phonon stop bands can be obtained by temporal and spatio
      temporal Fourier analysis. We further demonstrate how one can follow the temporal
      evolution of phononic eigenstates in k-space using data from phononic-crystal
      waveguides as an example. 

PMID- 26217055
TI  - Experimental model of topological defects in Minkowski space-time based on
      disordered ferrofluid: magnetic monopoles, cosmic strings and the space-time
      cloak.
AB  - In the presence of an external magnetic field, cobalt nanoparticle-based
      ferrofluid forms a self-assembled hyperbolic metamaterial. The wave equation,
      which describes propagation of extraordinary light inside the ferrofluid,
      exhibits 2+1 dimensional Lorentz symmetry. The role of time in the corresponding
      effective three-dimensional Minkowski space-time is played by the spatial
      coordinate directed along the periodic nanoparticle chains aligned by the
      magnetic field. Here, we present a microscopic study of point, linear, planar and
      volume defects of the nanoparticle chain structure and demonstrate that they may
      exhibit strong similarities with such Minkowski space-time defects as magnetic
      monopoles, cosmic strings and the recently proposed space-time cloaks.
      Experimental observations of such defects are described. 

PMID- 26217054
TI  - Spatial transformation-enabled electromagnetic devices: from radio frequencies to
      optical wavelengths.
AB  - Transformation optics provides scientists and engineers with a new powerful
      design paradigm to manipulate the flow of electromagnetic waves in a user-defined
      manner and with unprecedented flexibility, by controlling the spatial
      distribution of the electromagnetic properties of a medium. Using this approach,
      over the past decade, various previously undiscovered physical wave phenomena
      have been revealed and novel electromagnetic devices have been demonstrated
      throughout the electromagnetic spectrum. In this paper, we present versatile
      theoretical and experimental investigations on designing transformation optics
      enabled devices for shaping electromagnetic wave radiation and guidance, at both
      radio frequencies and optical wavelengths. Different from conventional coordinate
      transformations, more advanced and versatile coordinate transformations are
      exploited here to benefit diverse applications, thereby providing expanded design
      flexibility, enhanced device performance, as well as reduced implementation
      complexity. These design examples demonstrate the comprehensive capability of
      transformation optics in controlling electromagnetic waves, while the associated
      novel devices will open up new paths towards future integrated electromagnetic
      component synthesis and design, from microwave to optical spectral regimes. 

PMID- 26217056
TI  - Metasurface transformation for surface wave control.
AB  - Metasurfaces (MTSs) constitute a class of thin metamaterials used for controlling
      plane waves and surface waves (SWs). At microwave frequencies, they are
      constituted by a metallic texture with elements of sub-wavelength size printed on
      thin grounded dielectric substrates. These structures support the propagation of
      SWs. By averaging the tangential fields, the MTSs can be characterized through
      homogenized isotropic or anisotropic boundary conditions, which can be described
      through a homogeneous equivalent impedance. This impedance can be spatially
      modulated by locally changing the size/orientation of the texture elements. This
      allows for a deformation of the SW wavefront which addresses the local wavevector
      along not-rectilinear paths. The effect of the MTS modulation can be analysed in
      the framework of transformation optics. This article reviews theory and
      implementation of this MTS transformation and shows some examples at microwave
      frequencies. 

PMID- 26217057
TI  - Transformation optics beyond the manipulation of light trajectories.
AB  - Since its inception in 2006, transformation optics has become an established tool
      to understand and design electromagnetic systems. It provides a geometrical
      perspective into the properties of light waves without the need for a ray
      approximation. Most studies have focused on modifying the trajectories of light
      rays, e.g. beam benders, lenses, invisibility cloaks, etc. In this contribution,
      we explore transformation optics beyond the manipulation of light trajectories.
      With a few well-chosen examples, we demonstrate that transformation optics can be
      used to manipulate electromagnetic fields up to an unprecedented level. In the
      first example, we introduce an electromagnetic cavity that allows for deep
      subwavelength confinement of light. The cavity is designed with transformation
      optics even though the concept of trajectory ceases to have any meaning in a
      structure as small as this cavity. In the second example, we show that the
      properties of Cherenkov light emitted in a transformation-optical material can be
      understood and modified from simple geometric considerations. Finally, we show
      that optical forces--a quadratic function of the fields--follow the rules of
      transformation optics too. By applying a folded coordinate transformation to a
      pair of waveguides, optical forces can be enhanced just as if the waveguides were
      closer together. With these examples, we open up an entirely new spectrum of
      devices that can be conceived using transformation optics.

PMID- 26217058
TI  - Spatially variant periodic structures in electromagnetics.
AB  - Spatial transforms are a popular technique for designing periodic structures that
      are macroscopically inhomogeneous. The structures are often required to be
      anisotropic, provide a magnetic response, and to have extreme values for the
      constitutive parameters in Maxwell's equations. Metamaterials and photonic
      crystals are capable of providing these, although sometimes only approximately.
      The problem still remains about how to generate the geometry of the final lattice
      when it is functionally graded, or spatially varied. This paper describes a
      simple numerical technique to spatially vary any periodic structure while
      minimizing deformations to the unit cells that would weaken or destroy the
      electromagnetic properties. New developments in this algorithm are disclosed that
      increase efficiency, improve the quality of the lattices and provide the ability
      to design aplanatic metasurfaces. The ability to spatially vary a lattice in this
      manner enables new design paradigms that are not possible using spatial
      transforms, three of which are discussed here. First, spatially variant self
      collimating photonic crystals are shown to flow unguided waves around very tight
      bends using ordinary materials with low refractive index. Second, multi-mode
      waveguides in spatially variant band gap materials are shown to guide waves
      around bends without mixing power between the modes. Third, spatially variant
      anisotropic materials are shown to sculpt the near-field around electric
      components. This can be used to improve electromagnetic compatibility between
      components in close proximity. 

PMID- 26217059
TI  - Graded metascreens to enable a new degree of nanoscale light management.
AB  - Optical metasurfaces, typically referred to as two-dimensional metamaterials, are
      arrays of engineered subwavelength inclusions suitably designed to tailor the
      light properties, including amplitude, phase and polarization state, over deeply
      subwavelength scales. By exploiting anomalous localized interactions of surface
      elements with optical waves, metasurfaces can go beyond the functionalities
      offered by conventional diffractive optical gratings. The innate simplicity of
      implementation and the distinct underlying physics of their wave-matter
      interaction distinguish metasurfaces from three-dimensional metamaterials and
      provide a valuable means of moulding optical waves in the desired manner. Here,
      we introduce a general approach based on the electromagnetic equivalence
      principle to develop and synthesize graded, non-periodic metasurfaces to generate
      arbitrarily prescribed distributions of electromagnetic waves. Graded
      metasurfaces are realized with a single layer of spatially modulated,
      electrically polarizable nanoparticles, tailoring the scattering response of the
      surface with nanoscale resolutions. We discuss promising applications based on
      the proposed local wave management technique, including the design of ultrathin
      optical carpet cloaks, alignment-free polarization beam splitters and a novel
      approach to enable broadband light absorption enhancement in thin-film solar
      cells. This concept opens up a practical route towards efficient planarized
      optical structures with potential impact on the integrated nanophotonic
      technology. 

PMID- 26217060
TI  - A new look at the transformation electromagnetics approach for some real-world
      applications.
AB  - In this paper, we present an alternative approach to addressing the problem of
      designing a number of practical 'microwave' devices such as blankets serving as
      absorbers for radar targets, flat lenses and reflectarrays. 

PMID- 26217061
TI  - Spatial transformations: from fundamentals to applications.
AB  - This paper forms the introduction to this themed issue of Philosophical
      Transactions of the Royal Society A on 'Spatial transformations', arising from
      the Royal Society Scientific Discussion Meeting held in January 2015. The paper
      begins with a review of the concepts and history of spatial transformations,
      followed by a discussion of the contributions from the papers in this themed
      issue. A summary of the advantages and current limitations of spatial
      transformations concludes the paper, with the key challenges identified at the
      Scientific Discussion Meeting also given. 

PMID- 26217062
TI  - On cosmology in the laboratory.
AB  - In transformation optics, ideas from general relativity have been put to
      practical use for engineering problems. This article asks the question how this
      debt can be repaid. In discussing a series of recent laboratory experiments, it
      shows how insights from wave phenomena shed light on the quantum physics of the
      event horizon. 

PMID- 26217063
TI  - Two cases of spatial transformations.
AB  - Here, we give an overview of our work on two topics related to the theme of
      spatial transformations in wave theory, namely the concepts of transformation
      electronics and 'digital' metamaterials. In the first topic, we show that the
      notion of transformation optics can be extended to other physical phenomena such
      as tailoring the effective mass of charged carriers, e.g. electrons, in specially
      designed semiconductor superlattices. We discuss how the combination of thin
      layers of electronic materials with different effective mass of electrons may
      lead to bulk composite structures in which the effective mass of electrons may
      exhibit extreme anisotropy. For the second case, we show that any desired
      electromagnetic permittivity can, in principle, be engineered with proper
      combinations of two deeply subwavelength building blocks with relative
      permittivity values whose real parts have opposite signs. Owing to the presence
      of a plasmonic resonance between the two building blocks with oppositely signed
      dielectric constants, the achieved effective relative permittivity for the bulk
      composite may have values outside the range defined by the two permittivity
      values of the building blocks. We discuss some of the salient features of these
      two spatial transformation phenomena. 

PMID- 26217064
TI  - Readily processed protonic ceramic fuel cells with high performance at low
      temperatures.
AB  - Because of the generally lower activation energy associated with proton
      conduction in oxides compared to oxygen ion conduction, protonic ceramic fuel
      cells (PCFCs) should be able to operate at lower temperatures than solid oxide
      fuel cells (250 degrees  to 550 degrees C versus >=600 degrees C) on hydrogen and
      hydrocarbon fuels if fabrication challenges and suitable cathodes can be
      developed. We fabricated the complete sandwich structure of PCFCs directly from
      raw precursor oxides with only one moderate-temperature processing step through
      the use of sintering agents such as copper oxide. We also developed a proton-,
      oxygen-ion-, and electron-hole-conducting PCFC-compatible cathode material,
      BaCo(0.4)Fe(0.4)Zr(0.1)Y(0.1)O(3-delta) (BCFZY0.1), that greatly improved oxygen
      reduction reaction kinetics at intermediate to low temperatures. We demonstrated
      high performance from five different types of PCFC button cells without
      degradation after 1400 hours. Power densities as high as 455 milliwatts per
      square centimeter at 500 degrees C on H2 and 142 milliwatts per square centimeter
      on CH4 were achieved, and operation was possible even at 350 degrees C.

PMID- 26217065
TI  - REVIVE Trial: Retrograde Delivery of Autologous Bone Marrow in Patients With
      Heart Failure.
AB  - Cell therapy is an evolving option for patients with end-stage heart failure and
      ongoing symptoms despite optimal medical therapy. Our goal was to evaluate
      retrograde bone marrow cell delivery in patients with either ischemic heart
      failure (IHF) or nonischemic heart failure (NIHF). This was a prospective
      randomized, multicenter, open-label study of the safety and feasibility of bone
      marrow aspirate concentrate (BMAC) infused retrograde into the coronary sinus.
      Sixty patients were stratified by IHF and NIHF and randomized to receive either
      BMAC infusion or control (standard heart failure care) in a 4:1 ratio.
      Accordingly, 24 subjects were randomized to the ischemic BMAC group and 6 to the
      ischemic control group. Similarly, 24 subjects were randomized to the nonischemic
      BMAC group and 6 to the nonischemic control group. All 60 patients were
      successfully enrolled in the study. The treatment groups received BMAC infusion
      without complications. The left ventricular ejection fraction in the patients
      receiving BMAC demonstrated significant improvement compared with baseline, from
      25.1% at screening to 31.1% at 12 months (p=.007) in the NIHF group and from
      26.3% to 31.1% in the IHF group (p=.035). The end-systolic diameter decreased
      significantly in the nonischemic BMAC group from 55.6 to 50.9 mm (p=.020).
      Retrograde BMAC delivery is safe. All patients receiving BMAC experienced
      improvements in left ventricular ejection fraction, but only those with NIHF
      showed improvements in left ventricular end-systolic diameter and B-type
      natriuretic peptide. These results provide the basis for a larger clinical trial
      in HF patients. SIGNIFICANCE: This work is the first prospective randomized
      clinical trial using high-dose cell therapy delivered via a retrograde coronary
      sinus infusion in patients with heart failure. This was a multinational,
      multicenter study, and it is novel, translatable, and scalable. On the basis of
      this trial and the safety of retrograde coronary sinus infusion, there are three
      other trials under way using this route of delivery.

PMID- 26217066
TI  - Developmental implications of HIV prevention during adolescence: Examination of
      the long-term impact of HIV prevention interventions delivered in randomized
      controlled trials in grade six and in grade 10.
AB  - Dramatic changes occur in abstract reasoning, physical maturation, familial
      relationships and risk exposure during adolescence. It is probable that delivery
      of behavioral interventions addressing decision-making during the pre-adolescent
      period and later in adolescence would result in different impacts. We evaluated
      the intervention effects of an HIV prevention program (Bahamian Focus on Older
      Youth, BFOOY) administered to grade 10 Bahamian youth and parents to target HIV
      protective and risk behaviors. We also examined the effects of prior exposure to
      a similar intervention (Focus on Youth in the Caribbean, FOYC) four years
      earlier. At six months post-intervention, receipt of BFOOY by youth unexposed to
      FOYC increased HIV knowledge and condom-use skills. Differences based on BFOOY
      exposure were not present among FOYC-exposed youth, whose knowledge and condom
      use skills were already higher than those of unexposed youth. Youth receiving
      both interventions displayed a carryover effect from FOYC, demonstrating the
      highest scores six months post-intervention.

PMID- 26217067
TI  - Face Shape and Behavior: Implications of Similarities in Infants and Adults.
AB  - We investigated conceptual overlap between literature demonstrating links between
      adult facial width-to-height ratio (FWHR) and behavior and that demonstrating
      links between infant FWHR and temperament by investigating whether babyfaceness
      is associated with FWHR and behavior at both ages. Babyfaceness was positively
      correlated with FWHR in both infants and adults. Babyfaceness also was correlated
      with an infant temperament that is a precursor of bolder behavior in childhood
      and adulthood, just as a broader infant FWHR was previously shown to be. These
      results call into question existing explanations for relationships between facial
      appearance and adult assertive or aggressive behavior. Previously, behavioral
      correlates of adult FWHR have been attributed to influences of pubertal
      testosterone, and correlates of adult babyfaceness have been attributed to
      compensation for undesirable stereotypes. Our findings indicate that the pre
      natal developmental influences required to explain appearance-temperament
      relationships in infancy also should be considered as explanations for appearance
      behavior relationships in adulthood.

PMID- 26217069
TI  - 'Nature Concocts & Expels': The Agents and Processes of Recovery from Disease in
      Early Modern England.
AB  - The 'golden saying' in early modern medicine was 'Nature is the healer of
      disease'. This article uncovers the meaning and significance of this forgotten
      axiom by investigating perceptions of the agents and physiological processes of
      recovery from illness in England, c.1580-1720. Drawing on sources such as medical
      texts and diaries, it shows that doctors and laypeople attributed recovery to
      three agents-God, Nature and the practitioner. While scholars are familiar with
      the roles of providence and medicine, the vital agency of Nature has been
      overlooked. In theory, the agents operated in a hierarchy: Nature was 'God's
      instrument', and the physician, 'Nature's servant'; but in practice the power
      balance was more ambivalent. Nature was depicted both as a housewife who cooked
      and cleaned the humours, and as a warrior who defeated the disease. Through
      exploring these complex dynamics, the article sheds fresh light on concepts of
      gender, disease and bodies.

PMID- 26217068
TI  - The food retail revolution in China and its association with diet and health.
AB  - The processed food sector in low- and middle-income countries has grown rapidly.
      Little is understood about its effect on obesity. Using data from 14,976
      participants aged two and older in the 2011 China Health and Nutrition Survey,
      this paper examines patterns of processed food consumption and their impacts on
      obesity while considering the endogeneity of those who purchase processed foods.
      A major assumption of our analysis of the impact of processed foods on overweight
      and obesity was that the consumption of processed foods is endogenous due to
      their accessibility and urbanicity levels. The results show that 74.5% of
      participants consumed processed foods, excluding edible oils and other
      condiments; 28.5% of participants' total daily energy intake (EI) was from
      processed foods. Children and teenagers in megacities had the highest proportion
      of EI (40.2%) from processed foods. People who lived in megacities or highly
      urbanized neighborhoods with higher incomes and educational achievement consumed
      more processed foods. When controlling for endogeneity, only the body mass index
      (BMI) and risk of being overweight of children ages two to eighteen are adversely
      associated with processed foods (+4.97 BMI units, 95% confidence interval (CI):
      1.66-8.28; odds ratio (OR) = 3.63, 95% CI: 1.45-9.13). Processed food purchases
      represent less than a third of current Chinese food purchases. However, processed
      food purchases are growing at the rate of 50% per year, and we must begin to
      understand the implications for the future.

PMID- 26217070
TI  - Ignored Disease or Diagnostic Dustbin? Sudden Infant Death Syndrome in the
      British Context.
AB  - Sudden Infant Death Syndrome (SIDS) was defined in 1969 and incorporated into the
      International Classification of Diseases a decade later. To advocates of SIDS as
      a diagnosis, medical interest in sudden infant death was long overdue. However,
      the definition of SIDS lacked positive diagnostic criteria, provoking some to
      view it as a 'diagnostic dustbin' for the disposal of problematic cases where
      cause of death was unclear. This paper examines the development of medical
      interest in sudden infant death in Britain during the middle decades of the
      twentieth century. It highlights the importance of recognising the historicity of
      SIDS as a diagnosis facilitated by changes in law and medicine over the course of
      the nineteenth and twentieth centuries. It suggests that SIDS provides a
      definitive case study of the medicalisation of life and death, and a unique
      example of an officially recognised disease that had no symptoms, signs,
      pathology or patients.

PMID- 26217071
TI  - Inhaling Democracy: Cigarette Advertising and Health Education in Post-war West
      Germany, 1950s-1975.
AB  - In the late 1960s and early 1970s, the West German government was faced with the
      challenge of addressing a damaging health behaviour, smoking, in the context of
      an emerging late modern democracy, when the precedent for addressing that
      behaviour was set in the Nazi past. This paper details the two-pronged approach
      which the government took: seeking restrictions on cigarette advertising, whilst
      educating young people to adopt positive health behaviours in the face of
      pressure to smoke. This approach can be understood in the social and economic
      context of the time: an economic commitment to the social market economy worked
      against restrictions on the sale of cigarettes; whilst concerns about past
      authoritarian structures prompted the health authorities to seek novel ways of
      addressing smoking, emphasising choice. In a nuanced way, post-war anti-smoking
      strategies were a response to West Germany's National Socialist past, but more
      importantly, a signal of an increasingly international outlook.

PMID- 26217072
TI  - Sources and Resources Into the Dark Domain: The UK Web Archive as a Source for
      the Contemporary History of Public Health.
AB  - With the migration of the written record from paper to digital format, archivists
      and historians must urgently consider how web content should be conserved,
      retrieved and analysed. The British Library has recently acquired a large number
      of UK domain websites, captured 1996-2010, which is colloquially termed the Dark
      Domain Archive while technical issues surrounding user access are resolved. This
      article reports the results of an invited pilot project that explores
      methodological issues surrounding use of this archive. It asks how the
      relationship between UK public health and local government was represented on the
      web, drawing on the 'declinist' historiography to frame its questions. It points
      up some difficulties in developing an aggregate picture of web content due to
      duplication of sites. It also highlights their potential for thematic and
      discourse analysis, using both text and image, illustrated through an argument
      about the contradictory rationale for public health policy under New Labour.

PMID- 26217073
TI  - Non-celiac gluten sensitivity: Time for sifting the grain.
AB  - In the last few years, a new nomenclature has been proposed for the disease
      induced by the ingestion of gluten, a protein present in wheat, rice, barley and
      oats. Besides celiac disease and wheat allergy, the most studied forms of gluten
      related disorders characterized by an evident immune mechanism (autoimmune in
      celiac disease and IgE-mediated in wheat allergy), a new entity has been
      included, apparently not driven by an aberrant immune response: the non-celiac
      gluten sensitivity (NCGS). NCGS is characterized by a heterogeneous clinical
      picture with intestinal and extraintestinal symptoms arising after gluten
      ingestion and rapidly improving after its withdrawal from the diet. The
      pathogenesis of NCGS is largely unknown, but a mixture of factors such as the
      stimulation of the innate immune system, the direct cytotoxic effects of gluten,
      and probably the synergy with other wheat molecules, are clues for the
      complicated puzzle. In addition, the diagnostic procedures still remain
      problematic due to the absence of efficient diagnostic markers; thus, diagnosis
      is based upon the symptomatic response to a gluten-free diet and the recurrence
      of symptoms after gluten reintroduction with the possibility of an important
      involvement of a placebo effect. The temporary withdrawal of gluten seems a
      reasonable therapy, but the timing of gluten reintroduction and the correct
      patient management approach are have not yet been determined. 

PMID- 26217074
TI  - Genomic medicine in gastroenterology: A new approach or a new specialty?
AB  - Throughout history, many medical milestones have been achieved to prevent and
      treat human diseases. Man's early conception of illness was naturally holistic or
      integrative. However, scientific knowledge was atomized into quantitative and
      qualitative research. In the field of medicine, the main trade-off was the
      creation of many medical specialties that commonly treat patients in advanced
      stages of disease. However, now that we are immersed in the post-genomic era, how
      should we reevaluate medicine? Genomic medicine has evoked a medical paradigm
      shift based on the plausibility to predict the genetic susceptibility to disease.
      Additionally, the development of chronic diseases should be viewed as a continuum
      of interactions between the individual's genetic make-up and environmental
      factors such as diet, physical activity, and emotions. Thus, personalized
      medicine is aimed at preventing or reversing clinical symptoms, and providing a
      better quality of life by integrating the genetic, environmental and cultural
      factors of diseases. Whether using genomic medicine in the field of
      gastroenterology is a new approach or a new medical specialty remains an open
      question. To address this issue, it will require the mutual work of educational
      and governmental authorities with public health professionals, with the goal of
      translating genomic medicine into better health policies. 

PMID- 26217075
TI  - CREB-binding protein, p300, butyrate, and Wnt signaling in colorectal cancer.
AB  - This paper reviews the distinctive roles played by the transcriptional
      coactivators CREB-binding protein (CBP) and p300 in Wnt/beta-catenin signaling
      and cell physiology in colorectal cancer (CRC). Specifically, we focus on the
      effects of CBP- and p300-mediated Wnt activity on (1) neoplastic progression; (2)
      the activities of butyrate, a breakdown product of dietary fiber, on cell
      signaling and colonic cell physiology; (3) the development of resistance to
      histone deacetylase inhibitors (HDACis), including butyrate and synthetic HDACis,
      in colonic cells; and (4) the physiology and number of cancer stem cells.
      Mutations of the Wnt/beta-catenin signaling pathway initiate the majority of CRC
      cases, and we have shown that hyperactivation of this pathway by butyrate and
      other HDACis promotes CRC cell apoptosis. This activity by butyrate may in part
      explain the preventive action of fiber against CRC. However, individuals with a
      high-fiber diet may still develop neoplasia; therefore, resistance to the
      chemopreventive action of butyrate likely contributes to CRC. CBP or p300 may
      modify the ability of butyrate to influence colonic cell physiology since the two
      transcriptional coactivators affect Wnt signaling, and likely, its
      hyperactivation by butyrate. Also, CBP and p300 likely affect colonic
      tumorigenesis, as well as stem cell pluripotency. Improvement of CRC prevention
      and therapy requires a better understanding of the alterations in Wnt signaling
      and gene expression that underlie neoplastic progression, stem cell fate, and the
      development of resistance to butyrate and clinically relevant HDACis. Detailed
      knowledge of how CBP- and p300 modulate colonic cell physiology may lead to new
      approaches for anti-CRC prevention and therapeutics, particularly with respect to
      combinatorial therapy of CBP/p300 inhibitors with HDACis. 

PMID- 26217076
TI  - Management of hepatitis B virus infection during treatment for hepatitis B virus
      related hepatocellular carcinoma.
AB  - Although liver resection is considered the most effective treatment for
      hepatocellular carcinoma (HCC), treatment outcomes are unsatisfactory because of
      the high rate of HCC recurrence. Since we reported hepatitis B e-antigen
      positivity and high serum hepatitis B virus (HBV) DNA concentrations are strong
      risk factors for HCC recurrence after curative resection of HBV-related HCC in
      the early 2000s, many investigators have demonstrated the effects of viral status
      on HCC recurrence and post-treatment outcomes. These findings suggest controlling
      viral status is important to prevent HCC recurrence and improve survival after
      curative treatment for HBV-related HCC. Antiviral therapy after curative
      treatment aims to improve prognosis by preventing HCC recurrence and maintaining
      liver function. Therapy with interferon and nucleos(t)ide analogs may be useful
      for preventing HCC recurrence and improving overall survival in patients who have
      undergone curative resection for HBV-related HCC. In addition, reactivation of
      viral replication can occur after liver resection for HBV-related HCC. Antiviral
      therapy can be recommended for patients to prevent HBV reactivation.
      Nevertheless, further studies are required to establish treatment guidelines for
      patients with HBV-related HCC. 

PMID- 26217077
TI  - Grey zone in the Barcelona Clinic Liver Cancer Classification for hepatocellular
      carcinoma: Surgeons' perspective.
AB  - Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most
      common cause of cancer-related deaths worldwide. The Barcelona Clinic Liver
      Cancer (BCLC) classification has been endorsed as the optimal staging system and
      treatment algorithm for HCC by the European Association for the Study of Liver
      Disease and the American Association for the Study of Liver Disease. However, in
      real life, the majority of patients who are not considered ideal candidates based
      on the BCLC guideline still were performed hepatic resection nowadays, which
      means many hepatic surgeons all around the world do not follow the BCLC
      guidelines. The accuracy and application of the BCLC classification has
      constantly been challenged by many clinicians. From the surgeons' perspectives,
      we herein put forward some comments on the BCLC classification concerning
      subjectivity of the assessment criteria, comprehensiveness of the staging
      definition and accuracy of the therapeutic recommendations. We hope to further
      discuss with peers and colleagues with the aim to make the BCLC classification
      more applicable to clinical practice in the future. 

PMID- 26217078
TI  - Clusterin: Review of research progress and looking ahead to direction in
      hepatocellular carcinoma.
AB  - Liver cancer, a large proportion of which is hepatocellular carcinoma (HCC), is
      diagnosed in more than 700000 people each year worldwide. Liver cancer is
      particularly prevalent in Asia, Sub-Saharan Africa and the South Pacific, where
      hepatitis B and hepatitis C infection rates are very high. However, due to
      resistance to chemotherapy, patients with intermediate and advanced-stage disease
      cannot benefit from this treatment. Clusterin, which is overexpressed in many
      different cancers, is a stress-induced cytoprotective protein that confers
      treatment resistance. Custirsen (OGX-011) is a novel 2'-methoxyethyl modified
      phosphorothioate antisense oligonucleotide that targets secretory clusterin
      protein expression and is currently in clinical trials for patients with
      different cancers. In recent years, a number of different clinical trials have
      been performed, and two phase III clinical trials of custirsen evaluating
      combinations with chemotherapy in patients with metastatic castration-resistant
      prostate cancer and metastatic non-small cell lung cancer are currently in
      progress. The aims of this review are to summarize the current state of research
      on clusterin, predict future research directions and analyze the potential of the
      clinical application of custirsen in HCC. 

PMID- 26217079
TI  - Effects of Yttrium-90 selective internal radiation therapy on non-conventional
      liver tumors.
AB  - The liver is a common site of metastasis, with essentially all metastatic
      malignancies having been known to spread to the liver. Nearly half of all
      patients with extrahepatic primary cancer have hepatic metastases. The severe
      prognostic implications of hepatic metastases have made surgical resection an
      important first line treatment in management. However, limitations such as the
      presence of extrahepatic spread or poor functional hepatic reserve exclude the
      majority of patients as surgical candidates, leaving chemotherapy and
      locoregional therapies as next best options. Selective internal radiation therapy
      (SIRT) is a form of catheter-based locoregional cancer treatment modality for
      unresectable tumors, involving trans-arterial injection of microspheres embedded
      with a radio-isotope Yttrium-90. The therapeutic radiation dose is selectively
      delivered as the microspheres permanently embed themselves within the tumor
      vascular bed. Use of SIRT has been conventionally aimed at treating primary
      hepatic tumors (hepatocellular carcinoma) or colorectal and neuroendocrine
      metastases. Numerous reviews are available for these tumor types. However, little
      is known or reviewed on non-colorectal or non-neuroendocrine primaries.
      Therefore, the aim of this paper is to systematically review the current
      literature to evaluate the effects of Yttrium-90 radioembolization on non
      conventional liver tumors including those secondary to breast cancer,
      cholangiocarcinoma, ocular and percutaneous melanoma, pancreatic cancer, renal
      cell carcinoma, and lung cancer. 

PMID- 26217080
TI  - MicroRNAs potential utility in colon cancer: Early detection, prognosis, and
      chemosensitivity.
AB  - Over the past decade, research has shown that aberrant expression of microRNA
      (miRNA) is involved in colorectal cancer development and progression. MicroRNAs
      are small sequences of non-coding RNA that regulate expression of genes involved
      in important cellular functions, such as cell differentiation, multiplication,
      and apoptosis. A specific miRNA may display the effects of a tumor suppressor or
      oncogene. Altered miRNA expression is found in colorectal cancer (CRC) and
      patterns of miRNA expression correlate with CRC detection and outcome. Studies
      also have examined the use of circulating serum miRNA and fecal miRNA expression
      as non-invasive markers for early detection. Here, we review recent evidence
      demonstrating the potential role of miRNA in CRC and the implications of its use
      in the diagnosis, prognosis, and management of CRC. 

PMID- 26217081
TI  - Lipid dysregulation in hepatitis C virus, and impact of statin therapy upon
      clinical outcomes.
AB  - The hepatitis C virus (HCV) is one of the most common causes of chronic liver
      disease and the leading indication for liver transplantation worldwide. Every
      aspect of the HCV life cycle is closely tied to human lipid metabolism. The virus
      circulates as a lipid-rich particle, utilizing lipoprotein cell receptors to gain
      entry into the hepatocyte. It has also been shown to upregulate lipid
      biosynthesis and impair lipid degradation, resulting in significant intracellular
      lipid accumulation and circulating hypocholesterolemia. Patients with chronic
      hepatitis C (CHC) are at increased risk of hepatic steatosis, fibrosis, and
      cardiovascular disease including accelerated atherosclerosis. HMG CoA Reductase
      inhibitors, or statins, have been shown to play an important role in the
      modulation of hepatic steatosis and fibrosis, and recent attention has focused
      upon their potential therapeutic role in CHC. This article reviews the hepatitis
      C viral life cycle as it impacts host lipoproteins and lipid metabolism. It then
      describes the pathogenesis of HCV-related hepatic steatosis, hypocholesterolemia
      and atherosclerosis, and finally describes the promising anti-viral and anti
      fibrotic effects of statins, for the treatment of CHC. 

PMID- 26217082
TI  - Acupuncture and regulation of gastrointestinal function.
AB  - In China, acupuncture has been considered an effective method for treating
      gastrointestinal (GI) dysfunction diseases for thousands of years. In fact,
      acupuncture has gained progressive acceptance from both practitioners and
      patients worldwide. However, the therapeutic effects and underlying mechanisms in
      treating GI dysfunction have not yet been established due to a lack of systematic
      and comprehensive review articles. Therefore, the aim of this review is to
      discuss the efficacy of acupuncture as a treatment for GI dysfunction and the
      associated underlying mechanisms. A search of PubMed was conducted for articles
      that were published over the past 10 years using the terms "acupuncture",
      "gastrointestine", and other relevant keywords. In the following review, we
      describe the effect and underlying mechanisms of acupuncture on GI function from
      the perspectives of GI motility, visceral sensitivity, the GI barrier, and the
      brain-gut axis. The dual regulatory effects of acupuncture may manifest by
      promoting gastric peristalsis in subjects with low initial gastric motility, and
      suppressing peristalsis in subjects with active initial motility. In addition,
      the regulation of acupuncture on gastric motility may be intensity-dependent. Our
      findings suggest that further studies are needed to investigate the effects and
      more systematic mechanisms in treating GI dysfunction, and to promote the
      application of acupuncture for the treatment of GI diseases. 

PMID- 26217083
TI  - TLR4-HMGB1-, MyD88- and TRIF-dependent signaling in mouse intestinal
      ischemia/reperfusion injury.
AB  - AIM: To characterize high-mobility group protein 1-toll-like receptor 4 (HMGB1
      TLR4) and downstream signaling pathways in intestinal ischemia/reperfusion (I/R)
      injury. METHODS: Forty specific-pathogen-free male C57BL/6 mice were randomly
      divided into five groups (n = 8 per group): sham, control, anti-HMGB1, anti
      myeloid differentiation gene 88 (MyD88), and anti-translocating-chain-associating
      membrane protein (TRIF) antibody groups. Vehicle with the control IgG antibody,
      anti-HMGB1, anti-MyD88, or anti-TRIF antibodies (all 1 mg/kg, 0.025%) were
      injected via the caudal vein 30 min prior to ischemia. After anesthetization, the
      abdominal wall was opened and the superior mesenteric artery was exposed,
      followed by 60 min mesenteric ischemia and then 60 min reperfusion. For the sham
      group, the abdominal wall was opened for 120 min without I/R. Levels of serum
      nuclear factor (NF)-kappaB p65, interleukin (IL)-6, and tumor necrosis factor
      (TNF)-alpha were measured, along with myeloperoxidase activity in the lung and
      liver. In addition,morphologic changes that occurred in the lung and intestinal
      tissues were evaluated. Levels of mRNA transcripts encoding HMGB1 and NF-kappaB
      were measured by real-time quantitative PCR, and levels of HMGB1 and NF-kappaB
      protein were measured by Western blot. Results were analyzed using one-way
      analysis of variance. RESULTS: Blocking HMGB1, MyD88, and TRIF expression by
      injecting anti-HMGB1, anti-MyD88, or anti-TRIF antibodies prior to ischemia
      reduced the levels of inflammatory cytokines in serum; NF-kappaB p65: 104.64 +/-
      11.89, 228.53 +/- 24.85, 145.00 +/- 33.63, 191.12 +/- 13.22, and 183.73 +/- 10.81
      (P < 0.05); IL-6: 50.02 +/- 6.33, 104.91 +/- 31.18, 62.28 +/- 6.73, 85.90 +/-
      17.37, and 78.14 +/- 7.38 (P < 0.05); TNF-alpha, 43.79 +/- 4.18, 70.81 +/- 6.97,
      52.76 +/- 5.71, 63.19 +/- 5.47, and 59.70 +/- 4.63 (P < 0.05) for the sham,
      control, anti-HMGB1, anti-MyD88, and anti-TRIF groups, respectively (all in
      pg/mL).Antibodies also alleviated tissue injury in the lung and small intestine
      compared with the control group in the mouse intestinal I/R model. The
      administration of anti-HMGB1, anti-MyD88, and anti-TRIF antibodies markedly
      reduced damage caused by I/R, for which anti-HMGB1 antibody had the most obvious
      effect. CONCLUSION: HMGB1 and its downstream signaling pathway play important
      roles in the mouse intestinal I/R injury, and the effect of the TRIF-dependent
      pathway is slightly greater.

PMID- 26217084
TI  - Givinostat inhibition of hepatic stellate cell proliferation and protein
      acetylation.
AB  - AIM: To explore the effect of the histone deacetylase inhibitor givinostat on
      proteins related to regulation of hepatic stellate cell proliferation. METHODS:
      The cell counting kit-8 assay and flow cytometry were used to observe changes in
      proliferation, apoptosis, and cell cycle in hepatic stellate cells treated with
      givinostat. Western blot was used to observe expression changes in p21, p57,
      CDK4, CDK6, cyclinD1, caspase-3, and caspase-9 in hepatic stellate cells exposed
      to givinostat. The scratch assay was used to analyze the effect of givinostat on
      cell migration. Effects of givinostat on the reactive oxygen species profile,
      mitochondrial membrane potential, and mitochondrial permeability transition pore
      opening in JS-1 cells were observed by laser confocal microscopy. RESULTS:
      Givinostat significantly inhibited JS-1 cell proliferation and promoted cell
      apoptosis, leading to cell cycle arrest in G0/G1 phases. Treatment with
      givinostat downregulated protein expression of CDK4, CDK6, and cyclin D1, whereas
      expression of p21 and p57 was significantly increased. The givinostat-induced
      apoptosis of hepatic stellate cells was mainly mediated through p38 and
      extracellular signal-regulated kinase 1/2. Givinostat treatment increased
      intracellular reactive oxygen species production, decreased mitochondrial
      membrane potential, and promoted mitochondrial permeability transition pore
      opening. Acetylation of superoxide dismutase (acetyl K68) and nuclear factor
      kappaB p65 (acetyl K310) was upregulated, while there was no change in protein
      expression. Moreover, the notable beneficial effect of givinostat on liver
      fibrosis was also confirmed in the mouse models. CONCLUSION: Givinostat has
      antifibrotic activities via regulating the acetylation of nuclear factor-kappaB
      and superoxide dismutase 2, thus inhibiting hepatic stellate cell proliferation
      and inducing apoptosis.

PMID- 26217085
TI  - Potential protective effects of Clostridium butyricum on experimental gastric
      ulcers in mice.
AB  - AIM: To investigate the effects of Clostridium butyricum (C. butyricum) on
      experimental gastric ulcers (GUs) induced by alcohol, restraint cold stress, or
      pyloric ligation in mice, respectively. METHODS: One hundred and twenty mice were
      randomly allocated into three types of gastric ulcer models (n = 40 each),
      induced by alcohol, restraint cold stress, or pyloric ligation. In each GU model,
      40 mice were allocated into four groups (n = 10 each): the sham control group;
      model group (GU induction without pretreatment); C. butyricum group (GU induction
      with C. butyricum pretreatment); and Omeprazole group (GU induction with
      Omeprazole pretreatment). The effects of C. butyricum were evaluated by examining
      the histological changes in the gastric mucosal erosion area, the activities of
      superoxide dismutase (SOD) and catalase (CAT), the level of malondialdehyde
      (MDA), and the contents of interleukin (IL)-1beta, tumor necrosis factor (TNF)
      alpha, leukotriene B4 (LTB4) and 6-keto-PGF-1alpha (degradation product of PGI2)
      in the gastric tissue. RESULTS: Our data showed that C. butyricum significantly
      reduced the gastric mucosal injury area and ameliorated the pathological
      conditions of the gastric mucosa. C. butyricum not only minimized the decreases
      in activity of SOD and CAT, but also reduced the level of MDA in all three GU
      models used in this study. The accumulation of IL1-beta, TNF-alpha and LBT4
      decreased, while 6-keto-PGF-1alpha increased with pretreatment by C. butyricum in
      all three GU models. CONCLUSION: Our data demonstrated the protective effects of
      pretreatment with C. butyricum on anti-oxidation and anti-inflammation in
      different types of GU models in mice. Further studies are needed to explore its
      potential clinical benefits.

PMID- 26217086
TI  - Apoptosis of human pancreatic carcinoma cell-1 cells induced by Yin Chen Hao
      Decoction.
AB  - AIM: To evaluate human pancreatic carcinoma cell line (PANC-1) cells apoptosis
      and Bcl-2 and Bax expression induced by Yin Chen Hao Decoction (YCHD). METHODS:
      The cell growth inhibitory rate was determined by MTT assay. Apoptosis of PANC-1
      cells before and after treatment with YCHD was determined by TUNEL staining.
      Expression of the apoptosis-associated genes, Bcl-2 and Bax, was detected by
      immunohistochemical staining and reverse transcription -PCR. RESULTS: YCHD
      inhibited the growth of PANC-1 cells. Following treatment with YCHD for 24-96 h,
      the apoptotic rate of PANC-1 cells increased with time. In addition, the positive
      rate of Bcl-2 protein expression decreased in a time-dependent manner, whereas
      the positive rate of Bax protein expression increased in a time-dependent manner.
      Following treatment of with YCHD for 24-96h, expression of BAX mRNA increased
      gradually and BCL-2 mRNA reduced gradually with time. CONCLUSION: YCHD induces
      apoptosis of PANC-1 cells mediated in part via up-regulation of BAX and down
      regulation of BCL-2.

PMID- 26217087
TI  - Clinical features of second primary cancers arising in early gastric cancer
      patients after endoscopic resection.
AB  - AIM: To investigate the incidence and distribution of second primary cancers
      (SPCs) in early gastric cancer (EGC) patients who underwent endoscopic resection
      (ER), compared to advanced gastric cancer (AGC) patients who underwent surgery.
      METHODS: The medical records of 1021 gastric cancer (GC) patients were
      retrospectively reviewed from January 2006 to December 2010. The characteristics
      and incidence of SPCs were investigated in those with EGC that underwent curative
      ER (the EGC group) and those with AGC who underwent curative surgical resection
      (the AGC group). RESULTS: We ultimately enrolled 184 patients in the EGC group
      and 229 patients in the AGC group. A total of 38 of the 413 (9.2%) GC patients
      had SPCs; the rate was identical in both groups. Of these 38 patients, 18 had
      synchronous and 20 had metachronous cancers. The most common SPC was lung cancer
      (18.4%), followed by colorectal cancer (13.2%) and esophageal cancer (13.2%). No
      significant risk factors were identified for the development of SPCs. CONCLUSION:
      Endoscopists should provide close surveillance and establish follow-up programs
      to ensure SPC detection in GC patients undergoing curative resection regardless
      of their clinical characteristics.

PMID- 26217088
TI  - Effect of oral mesalamine on inflammatory response in acute uncomplicated
      diverticulitis.
AB  - AIM: To evaluate the impact of mesalamine administration on inflammatory response
      in acute uncomplicated diverticulitis. METHODS: We conducted a single centre
      retrospective cohort study on patients admitted to our surgical department
      between January 2012 and May 2014 with a computed tomography -confirmed diagnosis
      of acute uncomplicated diverticulitis. A total of 50 patients were included in
      the analysis, 20 (study group) had received 3.2 g/d of mesalamine starting from
      the day of admission in addition to the usual standard treatment, 30 (control
      group) had received standard therapy alone. Data was retrieved from a prospective
      database. Our primary study endpoints were: C reactive protein mean levels over
      time and their variation from baseline (DeltaCRP) over the first three days of
      treatment. Secondary end points included: mean white blood cell and neutrophile
      count over time, time before regaining of regular bowel movements (passing of
      stools), time before reintroduction of food intake, intensity of lower abdominal
      pain over time, analgesic consumption and length of hospital stay. RESULTS:
      Patients characteristics and inflammatory parameters were similar at baseline in
      the two groups. The evaluation of CRP levels over time showed, in treated
      patients, a distinct trend towards a faster decrease compared to controls. This
      difference approached statistical significance on day 2 (mean CRP 6.0 +/- 4.2
      mg/dL and 10.0 +/- 6.7 mg/dL respectively in study group vs controls, P = 0.055).
      DeltaCRP evaluation evidenced a significantly greater increment of this
      inflammatory marker in the control group on day 1 (P = 0.03). A similar trend
      towards a faster resolution of inflammation was observed evaluating the total
      white blood cell count. Neutrophile levels were significantly lower in treated
      patients on day 2 and on day 3 (P < 0.05 for both comparisons). Mesalamine
      administration was also associated with an earlier reintroduction of food intake
      (median 1.5 d and 3 d, study group vs controls respectively, P < 0.001) and with
      a shorter hospital stay (median 5 d and 5.5 d, study group vs controls
      respectively, P = 0.03). CONCLUSION: Despite its limitations, this study suggests
      that mesalamine may allow for a faster recovery and for a reduction of
      inflammatory response in acute uncomplicated diverticulitis.

PMID- 26217089
TI  - Score model for predicting acute-on-chronic liver failure risk in chronic
      hepatitis B.
AB  - AIM: To establish a clinical scoring model to predict risk of acute-on-chronic
      liver failure (ACLF) in chronic hepatitis B (CHB) patients. METHODS: This was a
      retrospective study of 1457 patients hospitalized for CHB between October 2008
      and October 2013 at the Beijing Ditan Hospital, Capital Medical University,
      China. The patients were divided into two groups: severe acute exacerbation (SAE)
      group (n = 382) and non-SAE group (n = 1075). The SAE group was classified as the
      high-risk group based on the higher incidence of ACLF in this group than in the
      non-SAE group (13.6% vs 0.4%). Two-thirds of SAE patients were randomly assigned
      to risk-model derivation and the other one-third to model validation. Univariate
      risk factors associated with the outcome were entered into a multivariate
      logistic regression model for screening independent risk factors. Each variable
      was assigned an integer value based on the regression coefficients, and the final
      score was the sum of these values in the derivation set. Model discrimination and
      calibration were assessed using area under the receiver operating characteristic
      curve and the Hosmer-Lemeshow test. RESULTS: The risk prediction scoring model
      included the following four factors: age >= 40 years, total bilirubin >= 171
      MUmol/L, prothrombin activity 40%-60%, and hepatitis B virus DNA > 10(7)
      copies/mL. The sum risk score ranged from 0 to 7; 0-3 identified patients with
      lower risk of ACLF, whereas 4-7 identified patients with higher risk. The Kaplan
      Meier analysis showed the cumulative risk for ACLF and ACLF-related death in the
      two risk groups (0-3 and 4-7 scores) of the primary cohort over 56 d, and log
      rank test revealed a significant difference (2.0% vs 33.8% and 0.8% vs 9.4%,
      respectively; both P < 0.0001). In the derivation and validation data sets, the
      model had good discrimination (C index = 0.857, 95% confidence interval: 0.800
      0.913 and C index = 0.889, 95% confidence interval: 0.820-0.957, respectively)
      and calibration demonstrated by the Hosmer-Lemeshow test (chi (2) = 4.516, P =
      0.808 and chi (2) = 1.959, P = 0.923, respectively). CONCLUSION: Using the
      scoring model, clinicians can easily identify patients (total score >= 4) at high
      risk of ACLF and ACLF-related death early during SAE.

PMID- 26217090
TI  - Demethylation of tumor necrosis factor-alpha converting enzyme promoter
      associated with high hepatitis B e antigen level in chronic hepatitis B.
AB  - AIM: To evaluate tumor necrosis factor-alpha converting enzyme (TACE) methylation
      status in patients with chronic hepatitis B (CHB). METHODS: Eighty patients with
      hepatitis B e antigen (HBeAg)-positive CHB, 80 with HBeAg-negative CHB, and 40
      healthy controls (HCs) were randomly enrolled in this study. Genomic DNA was
      extracted from peripheral blood mononuclear cells and methylation status of TACE
      promoter was determined by methylation-specific polymerase chain reaction. The
      clinical and laboratory parameters were collected. RESULTS: One hundred and
      thirty of 160 patients with CHB (81.25%) and 38 of 40 HCs (95%) displayed TACE
      promoter methylation. The difference was significant (chi (2) = 4.501, P < 0.05).
      TACE promoter methylation frequency in HBeAg-positive CHB (58/80, 72.5%) was
      significantly lower than that in HBeAg-negative CHB (72/80, 90%; chi (2) = 8.041,
      P < 0.01) and HCs (chi (2) = 8.438, P < 0.01). However, no significant difference
      was observed in the methylation frequency between HBeAg-negative CHB and HCs (chi
      (2) = 0.873, P > 0.05). In the HBeAg-positive group, TACE methylation frequency
      was significantly negatively correlated with HBeAg (r = -0.602, P < 0.01),
      alanine aminotransferase (r = -0.461, P < 0.01) and aspartate aminotransferase (r
      = -0.329, P < 0.01). CONCLUSION: Patients with HBeAg-positive CHB have aberrant
      demethylation of the TACE promoter, which may potentially serve as a biomarker
      for HBeAg seroconversion.

PMID- 26217091
TI  - Anatomy and influence of the splenic artery in laparoscopic spleen-preserving
      splenic lymphadenectomy.
AB  - AIM: To investigate the splenic hilar vascular anatomy and the influence of
      splenic artery (SpA) type in laparoscopic total gastrectomy with spleen
      preserving splenic lymphadenectomy (LTGSPL). METHODS: The clinical anatomy data
      of 317 patients with upper- or middle-third gastric cancer who underwent LTGSPL
      in our hospital from January 2011 to December 2013 were collected. The patients
      were divided into two groups (concentrated group vs distributed group) according
      to the distance between the splenic artery's furcation and the splenic hilar
      region. Then, the anatomical layout, clinicopathologic characteristics,
      intraoperative variables, and postoperative variables were compared between the
      two groups. RESULTS: There were 205 patients with a concentrated type (64.7%) and
      112 patients with a distributed type (35.3%) SpA. There were 22 patients (6.9%)
      with a single branch of the splenic lobar vessels, 250 (78.9%) with 2 branches,
      43 (13.6%) with 3 branches, and 2 patients (0.6%) with multiple branches. Eighty
      seven patients (27.4%) had type I splenic artery trunk, 211 (66.6%) had type II,
      13 (4.1%) had type III, and 6 (1.9%) had type IV. The mean splenic hilar
      lymphadenectomy time (23.15 +/- 8.02 vs 26.21 +/- 8.84 min; P = 0.002), mean
      blood loss resulting from splenic hilar lymphadenectomy (14.78 +/- 11.09 vs 17.37
      +/- 10.62 mL; P = 0.044), and number of vascular clamps used at the splenic hilum
      (9.64 +/- 2.88 vs 10.40 +/- 3.57; P = 0.040) were significantly lower in the
      concentrated group than in the distributed group. However, the mean total
      surgical time, mean total blood loss, and the mean number of harvested splenic
      hilar lymph nodes were similar in both groups (P > 0.05 for each comparison).
      There were also no significant differences in clinicopathological and
      postoperative characteristics between the groups (P > 0.05). CONCLUSION: It is of
      value for surgeons to know the splenic hilar vascular anatomy when performing
      LTGSPL. Patients with concentrated type SpA may be optimal patients for training
      new surgeons.

PMID- 26217092
TI  - SLITRK3 expression correlation to gastrointestinal stromal tumor risk rating and
      prognosis.
AB  - AIM: To assess the influence of SLIT and NTRK-like family member 3 (SLITRK3) on
      the prognosis of gastrointestinal stromal tumor (GIST) and determine whether
      SLITRK3 can help improve current risk stratification systems. METHODS: We
      hypothesized that SLITRK3 could be used as a prognostic molecular biomarker for
      GIST. 35 fresh tumor samples and 417 paraffin-embedded specimens from GIST
      patients were utilized. SLITRK3 mRNA expression in GIST tumor tissue was detected
      by real-time polymerase chain reaction, and SLITRK3 protein levels were estimated
      by immunohistochemistry. The correlation of SLITRK3 expression with various tumor
      clinicopathological characteristics and follow-up data were analyzed. RESULTS:
      GIST tumors had high expression of SLITRK3 compared with adjacent normal tissues
      and the expression level gradually increased with risk grade. SLITRK3 protein
      expression was closely associated with gastrointestinal bleeding, tumor site,
      tumor size, mitotic index, and National Institutes of Health (NIH)
      classification. Survival analysis showed that SLITRK3 expression was closely
      correlated with overall survival and disease-free survival of GIST patients.
      Multivariate analysis also identified SLITRK3 expression, mitotic index, and NIH
      stage as significant risk factors of GIST recurrence. CONCLUSION: SLITRK3
      expression is a highly significant predictor of GIST recurrence and metastasis.
      Combinations of SLITRK3 and NIH stage have strong predictive and prognostic
      value, and are feasible markers for clinical practice in gastrointestinal stromal
      tumor.

PMID- 26217093
TI  - Gastric mucosa in Mongolian and Japanese patients with gastric cancer and
      Helicobacter pylori infection.
AB  - AIM: To investigate the characteristics of gastric cancer and gastric mucosa in a
      Mongolian population by comparison with a Japanese population. METHODS: A total
      of 484 Mongolian patients with gastric cancer were enrolled to study gastric
      cancer characteristics in Mongolians. In addition, a total of 208 Mongolian and
      3205 Japanese consecutive outpatients who underwent endoscopy, had abdominal
      complaints, no history of gastric operation or Helicobacter pylori eradication
      treatment, and no use of gastric secretion inhibitors such as histamine H2
      receptor antagonists or proton pump inhibitors were enrolled. This study was
      conducted with the approval of the ethics committees of all hospitals. The triple
      site biopsy method was used for the histologic diagnosis of gastritis and H.
      pylori infection in all Mongolian and Japanese cases. The infection rate of H.
      pylori and the status of gastric mucosa in H. pylori-infected patients were
      compared between Mongolian and Japanese subjects. Age (+/- 5 years), sex, and
      endoscopic diagnosis were matched between the two countries. RESULTS:
      Approximately 70% of Mongolian patients with gastric cancer were 50-79 years of
      age, and approximately half of the cancers were located in the upper part of the
      stomach. Histologically, 65.7% of early cancers exhibited differentiated
      adenocarcinoma, whereas 73.9% of advanced cancers displayed undifferentiated
      adenocarcinoma. The infection rate of H. pylori was higher in Mongolian than
      Japanese patients (75.9% vs 48.3%, P < 0.0001). When stratified by age, the
      prevalence was highest among young patients, and tended to decrease in patients
      aged 50 years or older. The anti-East-Asian CagA-specific antibody was negative
      in 99.4% of H. pylori-positive Mongolian patients. Chronic inflammation,
      neutrophil activity, glandular atrophy, and intestinal metaplasia scores were
      significantly lower in Mongolian compared to Japanese H. pylori-positive patients
      (P < 0.0001), with the exception of the intestinal metaplasia score of specimen
      from the greater curvature of the upper body. The type of gastritis changed from
      antrum-predominant gastritis to corpus-predominant gastritis with age in both
      populations. CONCLUSION: Gastric cancer was located in the upper part of the
      stomach in half of the Mongolian patients; Mongolian patients were infected with
      non-East-Asian-type H. pylori.

PMID- 26217094
TI  - Downregulation of KIF1B mRNA in hepatocellular carcinoma tissues correlates with
      poor prognosis.
AB  - AIM: To compare kinesin family member 1B (KIF1B) expression with
      clinicopathologic parameters and prognosis in hepatocellular carcinoma (HCC)
      patients. METHODS: KIF1B protein and mRNA expression was assessed in HCC and
      paracarcinomatous (PC) tissues from 68 patients with HCC using Western blot and
      quantitative real-time reverse transcription-PCR, respectively. Student's t-tests
      were used to analyze relationships between clinicopathologic parameters and KIF1B
      expression, the Kaplan-Meier method was used to analyze survival outcomes, and
      the log-rank test was used to compare survival differences between groups.
      RESULTS: Mean protein and mRNA levels of KIF1B were similar between HCC and PC
      tissues. However, HCC tissues with vein invasions had significantly lower KIF1B
      protein levels compared to those without vein invasions (2.30 +/- 0.82 relative
      units vs 2.77 +/- 0.84 relative units, P < 0.05). KIF1B protein levels in HCC
      tissues from patients with recurrence during the follow-up period were
      significantly lower than those without recurrence (2.31 +/- 0.92 relative units
      vs 2.80 +/- 0.80 relative units, P < 0.05). However, KIF1B protein and mRNA
      expression in HCC patients was not associated with other clinicopathologic
      parameters. Ratios of KIF1B mRNA expression in HCC tissues to those in PC tissues
      were correlated with overall survival (13.5 mo vs 20.0 mo, P < 0.05) and disease
      free survival (11.5 mo vs 19.5 mo, P < 0.05). CONCLUSION: Downregulation of KIF1B
      in HCC tissues is associated with poor prognosis; additional clinical studies are
      needed to confirm whether KIF1B can serve as a prognostic marker.

PMID- 26217095
TI  - Parameters affecting different acoustic radiation force impulse applications in
      the diagnosis of fibrotic liver changes.
AB  - AIM: To analyze the virtual touch tissue quantification (VTTQ) and virtual touch
      imaging quantification (VTIQ) techniques, and identify possible factors that may
      influence VTTQ and VTIQ measurements. METHODS: One hundred and eighty-six (104
      women/82 men) of 323 subjects met the inclusion criteria (age > 18 years, no
      history of chronic or gastrointestinal disease, body-mass index (BMI) < 30 kg/m2,
      a fasting period of at least three hours, no history of hepatotoxic
      pharmaceuticals, alcohol consumption < 24 g/d in men and < 12 g/d in women, and
      normal findings upon ultrasound examination of the abdomen). Measurements were
      taken at depths of 50 mm with VTTQ, 15 mm and 25 mm with VTIQ in the right
      hepatic lobe, and at 15 mm with only VTIQ in the left hepatic lobe. The examiner
      acquired six measurements per position, thereby giving 24 measurements in total.
      RESULTS: The 95% confidence intervals of mean were 1.23-1.29 m/s for VTTQ and
      1.29-1.37 m/s, 1.17-1.23 m/s, and 1.48-1.57 m/s for VTIQ in a depth of 15 mm and
      25 mm in the right hepatic lobe and 15 mm in the left hepatic lobe. Only
      superficial measurements in the right hepatic lobe with the VTIQ method exhibited
      an effect of age on shear wave velocity. Measurements acquired using the 6C1
      probe with the VTTQ method showed no dependence on BMI. By comparison, BMI
      influenced measurements taken with the VTIQ method using the 9L4 probe in the
      superficial and deep areas of the right hepatic lobe, as well as in the left
      hepatic lobe (P = 0.0160, P = 0.0019, P = 0.0173, respectively). Gender
      influenced measurements at depths of 50 mm with VTTQ and 25 mm with VTIQ in the
      right hepatic lobe (P = 0.0001, P = 0.0269). Significant differences were found
      between measurements with the 6C1 (VTTQ) and 9L4 probes (VTIQ) (P = 0.0067),
      between superficial and deep measurements (P < 0.0001), and between the right and
      left lobes of the liver (P < 0.0001). CONCLUSION: Measurements in the right lobe
      and deep regions are preferable. Gender differences must be considered. BMI must
      be considered when assessing VTIQ technology.

PMID- 26217096
TI  - Systematic review: Eosinophilic esophagitis in Asian countries.
AB  - AIM: To investigate the prevalence and the clinical characteristics of Asian
      patients with eosinophilic esophagitis. METHODS: We conducted a systematic search
      of the PubMed and Web of Science databases for original studies, case series, and
      individual case reports of eosinophilic esophagitis in Asian countries published
      from January 1980 to January 2015. We found 66 and 80 articles in the PubMed and
      Web of Science databases, respectively; 24 duplicate articles were removed. After
      excluding animal studies, articles not written in English, and meeting abstracts,
      25 articles containing 217 patients were selected for analysis. RESULTS: Sample
      size-weighted mean values were determined for all pooled prevalence data and
      clinical characteristics. The mean age of the adult patients with eosinophilic
      esophagitis was approximately 50 years, and 73% of these patients were male. They
      frequently presented with allergic diseases including bronchial asthma, allergic
      rhinitis, food allergy, and atopic dermatitis. Bronchial asthma was the most
      frequent comorbid allergic disease, occurring in 24% of patients with
      eosinophilic esophagitis. Dysphagia was the primary symptom reported; 44% of the
      patients complained of dysphagia. Although laboratory blood tests are not
      adequately sensitive for an accurate diagnosis of eosinophilic esophagitis,
      endoscopic examinations revealed abnormal findings typical of this disease,
      including longitudinal furrows and concentric rings, in 82% of the cases. One
      third of the cases responded to proton pump inhibitor administration. CONCLUSION:
      The characteristics of eosinophilic esophagitis in Asian patients were similar to
      those reported in Western patients, indicating that this disease displays a
      similar pathogenesis between Western and Asian patients.

PMID- 26217097
TI  - Outcomes of robotic vs laparoscopic hepatectomy: A systematic review and meta
      analysis.
AB  - AIM: To perform a systematic review and meta-analysis on robotic-assisted vs
      laparoscopic liver resections. METHODS: A systematic literature search was
      performed using PubMed, Scopus and the Cochrane Library Central. Participants of
      any age and sex, who underwent robotic or laparoscopic liver resection were
      considered following these criteria: (1) studies comparing robotic and
      laparoscopic liver resection; (2) studies reporting at least one perioperative
      outcome; and (3) if more than one study was reported by the same institute, only
      the most recent was included. The primary outcome measures were set for estimated
      blood loss, operative time, conversion rate, R1 resection rate, morbidity and
      mortality rates, hospital stay and major hepatectomy rates. RESULTS: A total of 7
      articles, published between 2010 and 2014, fulfilled the selection criteria. The
      laparoscopic approach was associated with a significant reduction in blood loss
      and lower operative time (MD = 83.96, 95%CI: 10.51-157.41, P = 0.03; MD = 68.43,
      95%CI: 39.22-97.65, P < 0.00001, respectively). No differences were found with
      respect to conversion rate, R1 resection rate, morbidity and hospital stay.
      CONCLUSION: Laparoscopic liver resection resulted in reduced blood loss and
      shorter surgical times compared to robotic liver resections. There was no
      difference in conversion rate, R1 resection rate, morbidity and length of
      postoperative stay.

PMID- 26217098
TI  - Unusual presentation of a pancreatic cyst resulting from osteosarcoma metastasis.
AB  - Pancreatic metastases are uncommon. They have been reported in lung cancer,
      gastrointestinal malignancies, breast cancer, renal cell carcinoma, melanoma,
      lymphoma and sarcoma, and usually have solid morphology. Cystic metastasis to the
      pancreas is even more rare with few case reports in the literature. However, with
      the increasing use of computed tomography and magnetic resonance imaging as well
      as endoscopic ultrasound, more such lesions may be detected. Metastasis to the
      pancreas from osteosarcoma is highly unusual, but can be seen with the increasing
      survival of patients with osteosarcoma. We present an extremely rare case of a
      predominantly cystic lesion of the pancreas, which was diagnosed as metastasis
      from osteosarcoma. The pathophysiology of the cystic component of the metastasis
      of osteosarcoma is unknown. Cystic necrotic degeneration of the solid metastasis
      or pancreatitis secondary to the metastasis with development of associated fluid
      collection can be considered. Metastasis should remain a differential
      consideration even for primarily cystic lesions of the pancreas. 

PMID- 26217099
TI  - Resected tumor seeding in stomach wall due to endoscopic ultrasonography-guided
      fine needle aspiration of pancreatic adenocarcinoma.
AB  - Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is a useful
      and relatively safe tool for the diagnosis and staging of pancreatic cancer.
      However, there have recently been several reports of tumor seeding after EUS-FNA
      of adenocarcinomas. A 78-year-old man was admitted to our hospital due to upper
      gastric pain. Examinations revealed a 20 mm mass in the pancreatic body, for
      which EUS-FNA was performed. The cytology of the lesion was adenocarcinoma, and
      the stage of the cancer was T3N0M0. The patient underwent surgery with curative
      intent, followed by adjuvant chemotherapy with S-1. An enlarging gastric
      submucosal tumor was found on gastroscopy at 28 mo after surgery accompanied by a
      rising level of CA19-9. Biopsy result was adenocarcinoma, consistent with a
      pancreatic primary tumor. Tumor seeding after EUS-FNA was strongly suspected. The
      patient underwent surgical resection of the gastric tumor with curative intent.
      The pathological result of the resected gastric specimen was adenocarcinoma with
      a perfectly matched mucin special stain result with the previously resected
      pancreatic cancer. This is the first case report of tumor seeding after EUS-FNA
      which was surgically resected and inspected pathologically. 

PMID- 26217100
TI  - Acute appendicitis following endoscopic mucosal resection of cecal adenoma.
AB  - Endoscopic mucosal resection (EMR) allows the removal of flat or sessile lesions,
      laterally spreading tumors, and carcinoma of the colon or the rectum limited to
      the mucosa or the superficial submucosa. Acute appendicitis is the most common
      abdominal emergency requiring emergency surgery, and it is also a rare
      complication of diagnostic colonoscopy and therapeutic endoscopy, including EMR.
      In the case presented here, a 53-year-old female underwent colonoscopy due to a
      positive fecal occult blood test and was diagnosed with cecal adenoma. She was
      referred to our hospital and admitted for treatment. The patient had no other
      symptoms. EMR was performed, and 7 h after the surgery, the patient experienced
      right -lower abdominal pain. Laboratory tests performed the following day
      revealed a WBC count of 16000/mm(3), a neutrophil count of 14144/mm(3), and a C
      reactive protein level of 2.20 mg/dL, indicating an inflammatory response.
      Computed tomography also revealed appendiceal wall thickening and swelling, so
      acute appendicitis following EMR was diagnosed. Antibiotics were initiated
      leading to total resolution of the symptoms, and the patient was discharged on
      the sixth post-operative day. Pathological analysis revealed a high-grade cecal
      tubular adenoma. Such acute appendicitis following EMR is extremely rare, and EMR
      of the cecum may be a rare cause of acute appendicitis. 

PMID- 26217101
TI  - Primary intestinal lymphangiectasia with generalized warts.
AB  - Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy
      with lymphatic leakage into the small intestine. Dilated lymphatics in the small
      intestinal wall and mesentery are observed in this disease. Laboratory tests of
      PIL patients revealed hypoalbuminemia, lymphocytopenia, hypogammaglobulinemia and
      increased stool alpha-1 antitrypsin clearance. Cell-mediated immunodeficiency is
      also present in PIL patients because of loss of lymphocytes. As a result, the
      patients are vulnerable to chronic viral infection and lymphoma. However, cases
      of PIL with chronic viral infection, such as human papilloma virus-induced warts,
      are rarely reported. We report a rare case of PIL with generalized warts in a 36
      year-old male patient. PIL was diagnosed by capsule endoscopy and colonoscopic
      biopsy with histological tissue confirmation. Generalized warts were observed on
      the head, chest, abdomen, back, anus, and upper and lower extremities, including
      the hands and feet of the patient. 

PMID- 26217102
TI  - Molecular Cloning of a Novel Bradykinin-Related Peptide from the Skin of Indian
      Bronzed Frog Hylarana Temporalis.
AB  - Bradykinin-related peptides (BRPs) constitute one of the most studied groups of
      bioactive peptides in amphibian skin secretions. The present study describes the
      successful isolation of a novel BRP (hylaranakinin TE) from the skin secretion of
      the Indian bronzed frog Hylarana temporalis. The deduced open reading frame
      consisted of 115 amino acid residues with a putative signal peptide of 22 amino
      acid residues, followed by a spacer region and mature peptide regions that encode
      for two BRPs: a canonical bradykinin R-9-R with a C-terminal extension of FVPASSL
      and Thr6-BK. The Thr6-BK reported in the present study had an unusual FP
      insertion in the N-terminal part and ended in FAPEII, which is very different
      from the IAPAIV sequence reported in other ranid frogs. Unlike the mammalian
      bradykinin and its precursor, amphibian BRPs and their precursors are extremely
      variable, as evident from the present study. This forms the first report of BRPs
      from Hylarana temporalis, endemic to India and Sri Lanka. 

PMID- 26217103
TI  - ESTs from Seeds to Assist the Selective Breeding of Jatropha curcas L. for Oil
      and Active Compounds.
AB  - We report here on the characterization of a cDNA library from seeds of Jatropha
      curcas L. at three stages of fruit maturation before yellowing. We sequenced a
      total of 2200 clones and obtained a set of 931 non-redundant sequences (unigenes)
      after trimming and quality control, ie, 140 contigs and 791 singlets with PHRED
      quality >=10. We found low levels of sequence redundancy and extensive metabolic
      coverage by homology comparison to GO. After comparison of 5841 non-redundant
      ESTs from a total of 13193 reads from GenBank with KEGG, we identified tags with
      nucleotide variations among J. curcas accessions for genes of fatty acid,
      terpene, alkaloid, quinone and hormone pathways of biosynthesis. More
      specifically, the expression level of four genes (palmitoyl-acyl carrier protein
      thioesterase, 3-ketoacyl-CoA thiolase B, lysophosphatidic acid acyltransferase
      and geranyl pyrophosphate synthase) measured by real-time PCR proved to be
      significantly different between leaves and fruits. Since the nucleotide
      polymorphism of these tags is associated to higher level of gene expression in
      fruits compared to leaves, we propose this approach to speed up the search for
      quantitative traits in selective breeding of J. curcas. We also discuss its
      potential utility for the selective breeding of economically important traits in
      J. curcas. 

PMID- 26217104
TI  - Cloning and Initial Functional Characterization of Mlk4alpha and Mlk4beta.
AB  - We have cloned a novel human mixed-lineage kinase gene, MLK4. Two alternatively
      spliced forms, MLK4alpha (580 aa) and MLK4beta (1036 aa), have been identified
      and mapped to chromosomal band 1q42. MLK4 shows high amino acid homology to the
      kinase catalytic domain of MLK3 (72%), MLK1 (71%) and MLK2 (69%). Strong
      expression of MLK4 was detected in the human pancreas and kidneys. pCMV-MLK4beta
      c-myc-tagged protein (human) was expressed in the cytoplasm and nucleus of
      transiently transfected COS-1 cells, while pCMV-MLK4alpha c-myc-tagged protein
      (human) was expressed in cytoplasm only. Both MLK4 isoforms reduced the colony
      formation ability of MCF7 cells by 85%-95% and almost totally suppressed cell
      proliferation in the CyQUANT cell proliferation assay. Human pCMV-MLK4beta
      transgenic mice expressed the MLK4beta in all tissues examined but no phenotypic
      abnormalities were observed. Thus, in this work, we present the cloning and
      sequencing of MLK4alpha and MLK4beta for the first time; the data obtained
      suggest that MLK4 may function as a MAP kinase. 

PMID- 26217105
TI  - Transcriptional Changes of Blood Eosinophils After Methacholine Inhalation
      Challenge in Asthmatics.
AB  - BACKGROUND: Methacholine challenge is commonly used within the asthma diagnostic
      algorithm. Methacholine challenge has recently been shown to induce airway
      remodelling in asthma via bronchoconstriction, without additional airway
      inflammation. We evaluated the effect of methacholine-induced bronchoconstriction
      on the peripheral whole-blood transcriptome. METHODS: Fourteen males with adult
      onset, occupational asthma, 26-77 years of age, underwent methacholine inhalation
      challenges. The concentration of methacholine eliciting a >=20% fall in FEV1
      (PC20) was determined. Blood was collected immediately prior to and two hours
      after challenge. Complete blood counts and leukocyte differentials were obtained.
      Transcriptome analysis was performed using Affymetrix GeneChip((r)) Human Gene
      1.0 ST arrays. Data were analyzed using robust LIMMA and SAM. The cell-specific
      Significance Analysis of Microarrays (csSAM) algorithm was used to deconvolute
      the gene expression data according to cell type. RESULTS: Microarray pathway
      analysis indicated that inflammatory processes were differentially affected.
      CsSAM identified 1,559 transcripts differentially expressed (all down-regulated)
      between pre- and post-methacholine in eosinophils at a false discovery cutoff of
      10%. Notable changes included the GOLGA5 and METTL2B genes and the protein
      ubiquitination and CCR3 pathways. CONCLUSIONS: We demonstrated significant
      changes in the peripheral blood eosinophil-specific transcriptome of asthmatics
      two hours after methacholine challenge. CCR3 and protein ubiquitination pathways
      are both significantly down-regulated.

PMID- 26217107
TI  - Inter-Laboratory Variability in Array-Based RNA Quantification Methods.
AB  - Ribonucleic acids (RNA) are hypothesized to have preceded their derivatives,
      deoxyribonucleic acids (DNA), as the molecular media of genetic information when
      life emerged on earth. Molecular biologists are accustomed to the dramatic
      effects a subtle variation in the ribose moiety composition between RNA and DNA
      can have on the stability of these molecules. While DNA is very stable after
      extraction from biological samples and subsequent treatment, RNA is notoriously
      labile. The short half-life property, inherent to RNA, benefits cells that do not
      need to express their entire repertoire of proteins. The cellular machinery turns
      off the production of a given protein by shutting down the transcription of its
      cognate coding gene and by either actively degrading the remaining mRNA or
      allowing it to decay on its own. The steady-state level of each mRNA in a given
      cell varies continuously and is specified by changing kinetics of synthesis and
      degradation. Because it is technically possible to simultaneously measure
      thousands of nucleic acid molecules, these quantities have been studied by the
      life sciences community to investigate a range of biological problems. Since the
      RNA abundance can change according to a wide range of perturbations, this makes
      it the molecule of choice for exploring biological systems; its instability, on
      the other hand, could be an underestimated source of technical variability. We
      found that a large fraction of the RNA abundance originally present in the
      biological system prior to extraction was masked by the RNA labeling and
      measurement procedure. The method used to extract RNA molecules from cells and to
      label them prior to hybridization operations on DNA arrays affects the original
      distribution of RNA. Only if RNA measurements are performed according to the same
      procedure can biological information be inferred from the assay read out. 

PMID- 26217106
TI  - The DNA Habitat and its RNA Inhabitants: At the Dawn of RNA Sociology.
AB  - Most molecular biological concepts derive from physical chemical assumptions
      about the genetic code that are basically more than 40 years old. Additionally,
      systems biology, another quantitative approach, investigates the sum of
      interrelations to obtain a more holistic picture of nucleotide sequence order.
      Recent empirical data on genetic code compositions and rearrangements by mobile
      genetic elements and noncoding RNAs, together with results of virus research and
      their role in evolution, does not really fit into these concepts and compel a
      reexamination. In this review, we try to find an alternate hypothesis. It seems
      plausible now that if we look at the abundance of regulatory RNAs and persistent
      viruses in host genomes, we will find more and more evidence that the key players
      that edit the genetic codes of host genomes are consortia of RNA agents and
      viruses that drive evolutionary novelty and regulation of cellular processes in
      all steps of development. This agent-based approach may lead to a qualitative RNA
      sociology that investigates and identifies relevant behavioral motifs of
      cooperative RNA consortia. In addition to molecular biological perspectives, this
      may lead to a better understanding of genetic code evolution and dynamics. 

PMID- 26217108
TI  - Comparative Genomics of Bacillus species and its Relevance in Industrial
      Microbiology.
AB  - With the advent of high throughput sequencing platforms and relevant analytical
      tools, the rate of microbial genome sequencing has accelerated which has in turn
      led to better understanding of microbial molecular biology and genetics. The
      complete genome sequences of important industrial organisms provide opportunities
      for human health, industry, and the environment. Bacillus species are the
      dominant workhorses in industrial fermentations. Today, genome sequences of
      several Bacillus species are available, and comparative genomics of this genus
      helps in understanding their physiology, biochemistry, and genetics. The genomes
      of these bacterial species are the sources of many industrially important enzymes
      and antibiotics and, therefore, provide an opportunity to tailor enzymes with
      desired properties to suit a wide range of applications. A comparative account of
      strengths and weaknesses of the different sequencing platforms are also
      highlighted in the review. 

PMID- 26217110
TI  - The role of the pathologist in the decision-making process.

PMID- 26217109
TI  - Optimal approach in early breast cancer: Adjuvant and neoadjuvant treatment.

PMID- 26217111
TI  - Optimal approach in early breast cancer: Radiation therapy.
AB  - Radiation therapy significantly reduces by at least 70% the relative risk of
      local and regional recurrences for breast cancer after surgery. A positive
      influence on overall survival has been clearly demonstrated, especially for
      patients with a high absolute risk for locoregional recurrences. However, this is
      partially counterbalanced by late toxicity (dependent upon the radiation dose)
      especially to cardiac structures. Apart from this toxicity, a clear influence of
      radiation-therapy-related factors on functional and cosmetic outcome has also
      been demonstrated. Over time, technical improvements have led to a marked
      reduction in dose to the neighbouring organs, with a consequent drop in acute and
      late toxicity. This has also allowed the introduction of shorter radiation
      schedules, lowering the burden of treatment to the patient and the hospital.
      Several tools, techniques and guidelines have been developed to optimise the
      balance between the desired reduction in recurrence rates and side effects. The
      multidisciplinary team should discuss all available treatment options for every
      individual breast cancer patient. Individualisation of the selection of the
      optimal combination of treatments, depending on patient and tumour-related
      factors, is of utmost importance. Apart from direct tumour-related outcomes,
      cosmesis and potential side effects have to be taken into account. Counselling
      should include known risk factors for survival and complications, including
      comorbidity. 

PMID- 26217112
TI  - Optimal imaging staging of rectal cancer.

PMID- 26217113
TI  - Neoadjuvant therapy before surgical treatment.
AB  - Neoadjuvant treatment in terms of preoperative radiotherapy reduces local
      recurrence in rectal cancer, but this improvement has little if any impact on
      overall survival. Currently performed optimal quality-controlled total mesorectal
      excision (TME) surgery for patients in the trial setting can be associated with
      very low local recurrence rates of less than 10% whether the patients receive
      radiotherapy or not. Hence metastatic disease is now the predominant issue. The
      concept of neoadjuvant chemotherapy (NACT) is a potentially attractive additional
      or alternative strategy to radiotherapy to deal with metastases. However,
      randomised phase III trials, evaluating the addition of oxaliplatin at low doses
      plus preoperative fluoropyrimidine-based chemoradiotherapy (CRT), have in the
      main failed to show a significant improvement on early pathological response,
      with the exception of the German CAO/ARO/AIO-04 study. The integration of
      biologically targeted agents into preoperative CRT has also not fulfilled
      expectations. The addition of cetuximab appears to achieve relatively low rates
      of pathological complete responses, and the addition of bevacizumab has raised
      concerns for excess surgical morbidity. As an alternative to concurrent
      chemoradiation (which delivers only 5-6 weeks of chemotherapy), potential options
      include an induction component of 6-12 weeks of NACT prior to radiotherapy or
      chemoradiation, or the addition of chemotherapy after short-course preoperative
      radiotherapy (SCPRT) or chemoradiation (defined as consolidation chemotherapy)
      which utilises the "dead space" of the interval between the end of chemoradiation
      and surgery, or delivering chemotherapy alone without any radiotherapy. 

PMID- 26217114
TI  - The modern anatomical surgical approach to localised rectal cancer.

PMID- 26217115
TI  - Adjuvant chemotherapy.

PMID- 26217117
TI  - Targeted therapy in melanoma - the role of BRAF, RAS and KIT mutations.
AB  - Melanoma today is considered as a spectrum of melanocytic malignancies
      characterised by clinical and molecular features, including targetable mutations
      in several kinases such as BRAF or c-KIT. The successful development of therapies
      targeting these mutations has resulted in new specific treatment options. These
      include vemurafenib, dabrafenib, trametinib, imatinib and other kinase inhibitors
      that are selected when the respective mutation is present. The BRAF inhibitor
      vemurafenib has resulted in improved survival in patients with BRAF-mutated
      advanced melanoma. Dabrafenib has shown similar efficacy. The MEK inhibitor
      trametinib also improved overall survival. In addition, the MEK inhibitor MEK 162
      was investigated in a phase II clinical trial and showed promising efficacy in
      terms of response rate and progression-free survival (PFS) in NRAS-mutated
      melanomas. After this first success in the treatment of advanced melanoma, there
      is expectation that combinations of kinase inhibitors will additionally improve
      overall survival rates and PFS in advanced melanoma. 

PMID- 26217116
TI  - Melanoma epidemiology, biology and prognosis.

PMID- 26217118
TI  - Immunotherapy of melanoma.
AB  - Melanoma is considered one of the immunogenic - if not the most immunogenic -
      malignancies. This is based on several observations.1.Spontaneous remissions
      occur occasionally.2.In about 5% of melanomas no primary tumour is found. The
      genetic aberrations of these tumours closely resemble those of cutaneous
      melanomas, and therefore are suggestive of spontaneous regressions of the primary
      tumours.3.Both primary tumours and metastases often have brisk lymphocytic
      infiltrates, a phenomenon that is correlated with better outcome.4.Studies of
      isolates of these tumour-infiltrating T lymphocytes have revealed that a
      proportion of these cells recognise melanoma antigens.5.Melanomas respond to
      immunotherapy. These observations have led to over 30 years of research on
      immunotherapy for melanoma; many of these efforts have failed, with only a few
      exceptions: interleukin-2 (IL-2) and to a lesser degree interferon-a (IFN-<).
      Recently, new developments in immunotherapy have revolutionised this treatment
      modality. Anti-CTLA4 has received approval from the Food and Drugs Administration
      (FDA) and the European Medicines Agency (EMA) for the treatment of stage IV
      melanomas based on the improvement in overall survival in phase III trials, and
      more recently blockade of PD1/PDL1 interactions has shown objective clinical
      responses in a stage IV melanoma in early-phase clinical trials. In addition,
      several independent single-institution phase I/II trials using adoptive cell
      therapy have shown a consistently high response rate, including durable complete
      remissions in a substantial percentage of treated patients. Now, for the first
      time, immunotherapy has moved beyond the treatment of melanoma as both CTLA4 and
      PD1 blockade have been shown to induce objective responses in other tumour types
      as well. This chapter will discuss the mechanism of action, clinical efficacy and
      side effects of IL-2, the novel treatments consisting of the immune checkpoint
      blockade drugs anti-CTLA4 and anti-PD1 and adoptive cell therapy. 

PMID- 26217119
TI  - Adjuvant therapy for high-risk melanoma.

PMID- 26217120
TI  - Surgical treatment of early-stage non-small-cell lung cancer.
AB  - Surgical resection remains the standard of care for functionally operable early
      stage non-small-cell lung cancer (NSCLC) and resectable stage IIIA disease. The
      role of invasive staging and restaging techniques is currently being debated, but
      they provide the largest biopsy samples which allow for precise mediastinal
      staging. Different types of operative procedures are currently available to the
      thoracic surgeon, and some of these interventions can be performed by video
      assisted thoracic surgery (VATS) with the same oncological results as those by
      open thoracotomy. The principal aim of surgical treatment for NSCLC is to obtain
      a complete resection which has been precisely defined by a working group of the
      International Association for the Study of Lung Cancer (IASLC). Intraoperative
      staging of lung cancer is of utmost importance to decide on the extent of
      resection according to the intraoperative tumour (T) and nodal (N) status.
      Systematic nodal dissection is generally advocated to evaluate the hilar and
      mediastinal lymph nodes which are subdivided into seven zones according to the
      most recent 7th tumour-node-metastasis (TNM) classification. Lymph-node
      involvement not only determines prognosis but also the administration of adjuvant
      therapy. In 2011, a new multidisciplinary adenocarcinoma classification was
      published introducing the concepts of adenocarcinoma in situ and minimally
      invasive adenocarcinoma. This classification has profound surgical implications.
      The role of limited or sublobar resection, comprising anatomical segmentectomy
      and wide wedge resection, is reconsidered for early-stage lesions which are more
      frequently encountered with the recently introduced large screening programmes.
      Numerous retrospective non-randomised studies suggest that sublobar resection may
      be an acceptable surgical treatment for early lung cancers, also when performed
      by VATS. More tailored, personalised therapy has recently been introduced.
      Quality-of-life parameters and surgical quality indicators become increasingly
      important to determine the short-term and long-term impact of a surgical
      procedure. International databases currently collect extensive surgical data,
      allowing more precise calculation of mortality and morbidity according to
      predefined risk factors. Centralisation of care has been shown to improve
      results. Evidence-based guidelines should be further developed to provide optimal
      staging and therapeutic algorithms. 

PMID- 26217122
TI  - Adjuvant chemotherapy of non-small-cell lung cancer.

PMID- 26217121
TI  - Role of adjuvant radiotherapy in completely resected non-small-cell lung cancer.
AB  - Most long-term survivors of non-small-cell lung cancer (NSCLC) are patients who
      have had a completely resected tumour. However, this is only achievable in about
      30% of the patients. Even in this highly selected group of patients, there is
      still a high risk of both local and distant failure. Adjuvant treatments such as
      chemotherapy (CT) and radiotherapy (RT) have therefore been evaluated in order to
      improve their outcome. In patients with stage II and III, administration of
      adjuvant platinum-based chemotherapy is now considered the standard of care,
      based on level 1 evidence. The role of postoperative radiation therapy (PORT)
      remains controversial. In the PORT meta-analysis published in 1998, the
      conclusions were that if PORT was detrimental to patients with stage I and II
      completely resected NSCLC, the role of PORT in the treatment of tumours with N2
      involvement was unclear and further research was warranted. Thus at present,
      after complete resection, adjuvant radiotherapy should not be administered in
      patients with early lung cancer. Recent retrospective and non-randomised studies,
      as well as subgroup analyses of recent randomised trials evaluating adjuvant
      chemotherapy, provide evidence of the possible benefit of PORT in patients with
      mediastinal nodal involvement. The role of PORT needs to be evaluated also for
      patients with proven N2 disease who undergo neoadjuvant chemotherapy followed by
      surgery. The risk of local recurrence for N2 patients varies between 20% and 60%.
      Based on currently available data, PORT should be discussed for fit patients with
      completely resected NSCLC with N2 nodal involvement, preferably after completion
      of adjuvant chemotherapy or after surgery if patients have had preoperative
      chemotherapy. There is a need for new randomised evidence to reassess PORT using
      modern three-dimensional conformal radiation technique, with attention to normal
      organ sparing, particularly lung and heart, to reduce the possible over-added
      toxicity. Quality assurance of radiotherapy as well as quality of surgery - and
      most particularly nodal exploration modality - should both be monitored. A new
      large multi-institutional randomised trial Lung ART evaluating PORT in this
      patient population is needed and is now under way. 

PMID- 26217124
TI  - The seventh tumour-node-metastasis staging system for lung cancer: Sequel or
      prequel?
AB  - Anatomical cancer extent is an important predictor of prognosis and determines
      treatment choices. In non-small-cell lung cancer (NSCLC) the tumour-node
      metastasis (TNM) classification developed by Pierre Denoix replaced in 1968 the
      Veterans Administration Lung cancer Group (VALG) classification, which was still
      in use for small-cell lung cancer (SCLC). Clifton Mountain suggested several
      improvements based on a database of mostly surgically treated United States (US)
      patients from a limited number of centres. This database was pivotal for a
      uniform reporting of lung cancer extent by the American Joint Committee of Cancer
      (AJCC) and the International Union against Cancer (IUCC), but it suffered
      increasingly from obsolete diagnostic and staging procedures and did not reflect
      new treatment modalities. Moreover, its findings were not externally validated in
      large Japanese and European databases, resulting in persisting controversies
      which could not be solved with the available database. The use of different
      mediastinal lymph-node maps in Japan, the (US) and Europe facilitated neither the
      exchange nor the comparison of treatment results. Peter Goldstraw, a United
      Kingdom (UK) thoracic surgeon, started the process of updating the sixth version
      in 1996 and brought it to a good end 10 years later. His goals were to improve
      the TNM system in lung cancer by addressing the ongoing controversies, to
      validate the modifications and additional descriptors, to validate the TNM for
      use in staging SCLC and carcinoid tumours, to propose a new uniform lymph-node
      map and to investigate the prognostic value of non-anatomical factors. A staging
      committee was formed within the International Association for the Study of Lung
      Cancer (IASLC) - which supervised the collection of the retrospective data from
      >100,000 patients with lung cancer - treated throughout the world between 1990
      and 2000, analyse them with the help of solid statistics and validate externally
      with the Surveillance, Epidemiology and End Results (SEER) database. The ten
      modifications and the mediastinal lymph-node map - which were proposed in 2007
      and adopted by the AJCC and IUCC in their respective seventh revision of the TNM
      system - were implemented as of 2010 and were rapidly adopted by the thoracic
      oncology community and cancer registries. As expected, not all controversies
      could be fully addressed, and the need for a prospective data set containing more
      granular information was felt early on. This data set of 25,000 consecutive
      incident cases will form the base for the eighth revision in 2017 and is
      currently being collected. Other threats are the role of stage migration and the
      increasing number of biological factors interfering with disease extent for
      prognostication. The latter issue will be addressed by the creation of a
      prognostic index, including several prognostic factors, of which stage will be
      one. For the time being, the seventh TNM classification is considered the gold
      standard for the description of disease extent, initial treatment allocation and
      the reporting of treatment results. The uniform use of the TNM descriptors and
      the lymph-node map by all involved in lung cancer care is to be considered a
      process indicator of quality. 

PMID- 26217123
TI  - Prognostic factors in resected lung carcinomas.

PMID- 26217125
TI  - Individualising treatment choices in a crowded treatment algorithm.

PMID- 26217126
TI  - Does a reasonable treatment approach beyond second-line exist?

PMID- 26217129
TI  - Depression in cancer patients.

PMID- 26217128
TI  - Integrating metastasectomy and stereotactic radiosurgery in the treatment of
      metastatic renal cell carcinoma.

PMID- 26217127
TI  - Understanding and managing toxicities of vascular endothelial growth factor
      (VEGF) inhibitors.

PMID- 26217130
TI  - Anxiety and sleep disorders in cancer patients.

PMID- 26217131
TI  - Chemotherapy-related changes in cognitive functioning.

PMID- 26217132
TI  - Drug-associated delirium in cancer patients.

PMID- 26217133
TI  - Prevention - Passive smoking and pregnancy.

PMID- 26217134
TI  - Molecular profile of lung cancer in never smokers.
AB  - Tobacco smoking is the most common cause of lung cancer, but approximately 10-25%
      of patients with lung cancer are life-long never smokers. The cause of lung
      cancer in never smokers is unknown, although tobacco-smoke exposure may play a
      role in some of these patients. Lung cancer that develops in the absence of
      significant tobacco-smoke exposure appears to be a unique disease entity with
      novel genomic and epigenomic alterations and activation of molecular pathways
      that are not generally seen in tobacco-smoke-induced lung cancer. These molecular
      alterations are very likely responsible for the unique clinico-pathological
      features of lung cancer in never smokers (LCINS), and some of these molecular
      alterations - such as the activating EGFR TK mutations and EML4-ALK fusion -
      significantly influence therapeutic choices and treatment outcomes. In the last
      few years there has been a number of studies exploring the molecular
      characteristics of LCINS, and some of them have reported new and significant
      findings. Here we review the key findings from these studies and discuss their
      potential therapeutic implications. 

PMID- 26217135
TI  - Bone metastases: Causes, consequences and therapeutic opportunities.

PMID- 26217136
TI  - Bone-targeted therapy in prostate cancer.

PMID- 26217137
TI  - Current role of human papillomavirus in head and neck oncology.

PMID- 26217138
TI  - Novel therapeutic targets in diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) represents the most frequent lymphoma
      subtype and is considered a heterogeneous diagnostic category [1]. Using gene
      expression profiling, two major molecular subtypes termed germinal centre B-cell
      like (GCB) DLBCL and activated B-cell-like (ABC) DLBCL can be distinguished [2].
      Their gene expression profiles suggest that they arise from B-cells at different
      stages of differentiation. The GCB DLBCLs appear to originate from germinal
      centre B-cells, whereas the ABC DLBCLs may arise from post-germinal-centre B
      cells that are in transition to being differentiated into plasma cells.
      Intriguingly, these two subtypes differ not only with respect to the expression
      of thousands of genes, but also utilise different oncogenic pathways and have
      significantly different survival rates following therapy [3,4]. ABC DLBCLs are
      characterised by inferior survival compared with GCB DLBCL patients when treated
      with a combined approach of the anti-CD20 antibody rituximab and CHOP
      chemotherapy [5]. 

PMID- 26217139
TI  - Novel teatment options in early-stage non-small-cell lung cancer.

PMID- 26217140
TI  - Oncoplastic surgery - Standard of care.

PMID- 26217141
TI  - Role of aggressive surgery for peritoneal metastases.

PMID- 26217142
TI  - At what price do we treat patients with testicular cancer?

PMID- 26217143
TI  - From novel insights in molecular biology to targeted treatment approaches in head
      and neck cancer.

PMID- 26217144
TI  - Metastatic melanoma: New paradigms of treatment and new toxicities.

PMID- 26217145
TI  - Radiotherapy for rectal cancer: Short course versus long course - When and how.

PMID- 26217146
TI  - State of the art in neoadjuvant therapy of breast cancer.

PMID- 26217147
TI  - Application of sentinel nodes in gynaecological cancer therapy.

PMID- 26217148
TI  - Best management of locally advanced inoperable breast cancer.

PMID- 26217149
TI  - Cancer invasion and resistance.

PMID- 26217150
TI  - Nurse navigation is helpful for cancer patients, but with some restrictions.

PMID- 26217151
TI  - Nutritional status in relation to treatment modalities.

PMID- 26217152
TI  - The best treatment for older patients with breast cancer.

PMID- 26217153
TI  - Mechanisms of treatment-related symptoms in cancer patients.

PMID- 26217154
TI  - Modern management of penile cancer.

PMID- 26217155
TI  - Practical tips and tricks with recently approved molecular targeted agents in non
      small-cell lung cancer.

PMID- 26217157
TI  - Therapeutic procedures in liver metastases: Conventional and future measures.

PMID- 26217156
TI  - Role of expert centres in the management of sarcomas.

PMID- 26217159
TI  - 2013 European Multidisciplinary Cancer Congress Education Book.

PMID- 26217158
TI  - Together we are better: Establishing a community oncology nursing programme to
      improve cancer care through shared working.

PMID- 26217160
TI  - Clinical considerations for biosimilar antibodies.
AB  - Biosimilar agents are approximate copies of branded biologic therapies. Since the
      first biosimilar was authorized in the European Union in 2006, fifteen additional
      agents have been approved by the European Medicines Agency, including two
      biosimilar monoclonal antibodies (mAbs). Biosimilar mAbs represent a distinct
      class given their large molecular size, complex protein structure, and post
      translational modifications. While guidelines have been established for the
      development, approval, and use of biosimilars, further scrutiny and discussion is
      necessary to fully understand their potential impact on clinical outcomes. This
      review takes a critical look at the structural complexity of biosimilar mABs, the
      feasibility of indication extrapolation, the impact of product variability on
      immunogenicity, the importance of comprehensive pharmacovigilance, and the
      potential for ongoing pharmacoeconomic impact. 

PMID- 26217161
TI  - Cancer survivorship: A positive side-effect of more successful cancer treatment.
AB  - Over the past decades, early diagnosis, new drugs and more personalised multi
      modality treatment have led to impressive increases in survival rates of patients
      with cancer. This success in treating cancer has resulted in a large and rapidly
      increasing number of cancer survivors, yet life after cancer is often compromised
      by a broad spectrum of late adverse treatment effects. Some encounter
      cardiovascular, second malignancies, cognitive or other morbidities which impair
      normal life in an important way. Some patients are confronted with societal
      discrimination due to slower performance, chronic fatigue or partial inability
      and these things can adversely affect employment, education, insurance or
      mortgage opportunities. In 2012, the European Organisation of Research and
      Treatment of Cancer (EORTC) Survivorship Task Force was created to focus research
      efforts on late morbidity of cancer treatment and its impact on society. On 30
      31st January 2014, the 1st EORTC Cancer Survivorship Summit was organised to
      facilitate interaction between clinicians, researchers, social workers, patients,
      insurers, bankers and policy makers. This important event addressed the needs of
      cancer survivors, and new collaborations between academic groups, patient
      advocates, financial and political representatives were formed to guide future
      European research and health policies in this field. This special issue of the
      European Journal of Cancer is entirely dedicated to this Summit and addresses,
      respectively, second malignancies, cardiovascular disease, cognitive dysfunction,
      infertility/sexuality and psycho-social problems following cancer treatment. 

PMID- 26217162
TI  - Current knowledge and future research directions in treatment-related second
      primary malignancies.
AB  - Currently, 17-19% of all new primary malignancies occur in survivors of cancer,
      causing substantial morbidity and mortality. Research has shown that cancer
      treatments are important contributors to second malignant neoplasm (SMN) risk. In
      this paper we summarise current knowledge with regard to treatment-related SMNs
      and provide recommendations for future research. We address the risks associated
      with radiotherapy and systemic treatments, modifying factors of treatment-related
      risks (genetic susceptibility, lifestyle) and the potential benefits of screening
      and interventions. Research priorities were identified during a workshop at the
      2014 Cancer Survivorship Summit organised by the European Organisation for
      Research and Treatment of Cancer. Recently, both systemic cancer treatments and
      radiotherapy approaches have evolved rapidly, with the carcinogenic potential of
      new treatments being unknown. Also, little knowledge is available about modifying
      factors of treatment-associated risk, such as genetic variants and lifestyle.
      Therefore, large prospective studies with biobanking, high quality treatment data
      (radiation dose-volume, cumulative drug doses), and data on other cancer risk
      factors are needed. International collaboration will be essential to have
      adequate statistical power for such investigations. While screening for SMNs is
      included in several follow-up guidelines for cancer survivors, its effectiveness
      in this special population has not been demonstrated. Research into the
      pathogenesis, tumour characteristics and survival of SMNs is essential, as well
      as the development of interventions to reduce SMN-related morbidity and
      mortality. Prediction models for SMN risk are needed to inform initial treatment
      decisions, balancing chances of cure and SMNs and to identify high-risk subgroups
      of survivors eligible for screening. 

PMID- 26217163
TI  - Cardiovascular disease after cancer therapy.
AB  - Improvements in treatment and earlier diagnosis have both contributed to
      increased survival for many cancer patients. Unfortunately, many treatments carry
      a risk of late effects including cardiovascular diseases (CVDs), possibly leading
      to significant morbidity and mortality. In this paper we describe current
      knowledge of the cardiotoxicity arising from cancer treatments, outline gaps in
      knowledge, and indicate directions for future research and guideline development,
      as discussed during the 2014 Cancer Survivorship Summit organised by the European
      Organisation for Research and Treatment of Cancer (EORTC). Better knowledge is
      needed of the late effects of modern systemic treatments and of radiotherapy to
      critical structures of the heart, including the effect of both radiation dose and
      volume of the heart exposed. Research elucidating the extent to which treatments
      interact in causing CVD, and the mechanisms involved, as well as the extent to
      which treatments may increase CVD indirectly by increasing cardiovascular risk
      factors is also important. Systematic collection of data relating treatment
      details to late effects is needed, and great care is needed to obtain valid and
      generalisable results. Better knowledge of these cardiac effects will contribute
      to both primary and secondary prevention of late complications where exposure to
      cardiotoxic treatment is unavoidable. Also surrogate markers would help to
      identify patients at increased risk of cardiotoxicity. Evidence-based screening
      guidelines for CVD following cancer are also needed. Finally, risk prediction
      models should be developed to guide primary treatment choice and appropriate
      follow up after cancer treatment. 

PMID- 26217164
TI  - Monitoring and optimising cognitive function in cancer patients: Present
      knowledge and future directions.
AB  - The potentially detrimental effects of cancer and related treatments on cognitive
      functioning are emerging as a key focus of cancer survivorship research. Many
      patients with central nervous system (CNS) or non-CNS tumours develop cognitive
      problems during the course of their disease that can result in diminished
      functional independence. We review the state of knowledge on the cognitive
      functioning of patients with primary and secondary brain tumours at diagnosis,
      during and after therapy, and discuss current initiatives to diminish cognitive
      decline in these patients. Similarly, attention is paid to the cognitive sequelae
      of cancer and cancer therapies in patients without CNS disease. Disease and
      treatment effects on cognition are discussed, as well as current insights into
      the neural substrates and the mechanisms underlying cognitive dysfunction in
      these patients. In addition, rehabilitation strategies for patients with non-CNS
      disease confronted with cognitive dysfunction are described. Special attention is
      given to knowledge gaps in the area of cancer and cognition, in CNS and non-CNS
      diseases. Finally, we point to the important role for cooperative groups to
      include cognitive endpoints in clinical trials in order to accelerate our
      understanding and treatment of cognitive dysfunction related to cancer and cancer
      therapies. 

PMID- 26217166
TI  - Beyond treatment - Psychosocial and behavioural issues in cancer survivorship
      research and practice.
AB  - The population of cancer survivors has grown steadily over the past several
      decades. Surviving cancer, however, is not synonymous with a life free of
      problems related to the disease and its treatment. In this paper we provide a
      brief overview of selected physical and psychosocial health problems prevalent
      among cancer survivors, namely pain, fatigue, psychological distress and work
      participation. We also address issues surrounding self-management and e-Health
      interventions for cancer survivors, and programmes to encourage survivors to
      adopt healthier lifestyles. Finally, we discuss approaches to assessing health
      related quality of life in cancer survivors, and the use of cancer registries in
      conducting psychosocial survivorship research. We highlight research and practice
      priorities in each of these areas. While the priorities vary per topic, common
      themes that emerged included: (1) Symptoms should not be viewed in isolation, but
      rather as part of a cluster of interrelated symptoms. This has implications for
      both understanding the aetiology of symptoms and for their treatment; (2)
      Psychosocial interventions need to be evidence-based, and where possible should
      be tailored to the needs of the individual cancer survivor. Relatively low cost
      interventions with self-management and e-Health elements may be appropriate for
      the majority of survivors, with resource intensive interventions being reserved
      for those most in need; (3) More effort should be devoted to disseminating and
      implementing interventions in practice, and to evaluating their cost
      effectiveness; and (4) Greater attention should be paid to the needs of
      vulnerable and high-risk populations of survivors, including the
      socioeconomically disadvantaged and the elderly. 

PMID- 26217167
TI  - Epigenetic Determinism in Science and Society.
AB  - The epigenetic "revolution" in science cuts across many disciplines, and it is
      now one of the fastest growing research areas in biology. Increasingly, claims
      are made that epigenetics research represents a move away from the genetic
      determinism that has been prominent both in biological research and in
      understandings of the impact of biology on society. We discuss to what extent an
      epigenetic framework actually supports these claims. We show that, in contrast to
      the received view, epigenetics research is often couched in language as
      deterministic as genetics research in both science and the popular press. We
      engage the rapidly emerging conversation about the impact of epigenetics on
      public discourse and scientific practice, and we contend that the notion of
      epigenetic determinism - or the belief that epigenetic mechanisms determine the
      expression of human traits and behaviors - matters for understandings of the
      influence of biology and society on population health.

PMID- 26217165
TI  - Sexual dysfunction and infertility as late effects of cancer treatment.
AB  - Sexual dysfunction is a common consequence of cancer treatment, affecting at
      least half of men and women treated for pelvic malignancies and over a quarter of
      people with other types of cancer. Problems are usually linked to damage to
      nerves, blood vessels, and hormones that underlie normal sexual function. Sexual
      dysfunction also may be associated with depression, anxiety, relationship
      conflict, and loss of self-esteem. Innovations in cancer treatment such as
      robotic surgery or more targeted radiation therapy have not had the anticipated
      result of reducing sexual dysfunction. Some new and effective cancer treatments,
      including aromatase inhibitors for breast cancer or chemoradiation for anal
      cancer also have very severe sexual morbidity. Cancer-related infertility is an
      issue for younger patients, who comprise a much smaller percentage of total
      cancer survivors. However, the long-term emotional impact of being unable to have
      a child after cancer can be extremely distressing. Advances in knowledge about
      how cancer treatments may damage fertility, as well as newer techniques to
      preserve fertility, offer hope to patients who have not completed their
      childbearing at cancer diagnosis. Unfortunately, surveys in industrialised
      nations confirm that many cancer patients are still not informed about potential
      changes to their sexual function or fertility, and all modalities of fertility
      preservation remain underutilised. After cancer treatment, many patients continue
      to have unmet needs for information about restoring sexual function or becoming a
      parent. Although more research is needed on optimal clinical practice, current
      studies suggest a multidisciplinary approach, including both medical and
      psychosocial treatment options. 

PMID- 26217169
TI  - Robustness of spiking Deep Belief Networks to noise and reduced bit precision of
      neuro-inspired hardware platforms.
AB  - Increasingly large deep learning architectures, such as Deep Belief Networks
      (DBNs) are the focus of current machine learning research and achieve state-of
      the-art results in different domains. However, both training and execution of
      large-scale Deep Networks require vast computing resources, leading to high power
      requirements and communication overheads. The on-going work on design and
      construction of spike-based hardware platforms offers an alternative for running
      deep neural networks with significantly lower power consumption, but has to
      overcome hardware limitations in terms of noise and limited weight precision, as
      well as noise inherent in the sensor signal. This article investigates how such
      hardware constraints impact the performance of spiking neural network
      implementations of DBNs. In particular, the influence of limited bit precision
      during execution and training, and the impact of silicon mismatch in the synaptic
      weight parameters of custom hybrid VLSI implementations is studied. Furthermore,
      the network performance of spiking DBNs is characterized with regard to noise in
      the spiking input signal. Our results demonstrate that spiking DBNs can tolerate
      very low levels of hardware bit precision down to almost two bits, and show that
      their performance can be improved by at least 30% through an adapted training
      mechanism that takes the bit precision of the target platform into account.
      Spiking DBNs thus present an important use-case for large-scale hybrid analog
      digital or digital neuromorphic platforms such as SpiNNaker, which can execute
      large but precision-constrained deep networks in real time. 

PMID- 26217168
TI  - A Journey Through a Leaf: Phenomics Analysis of Leaf Growth in Arabidopsis
      thaliana.
AB  - In Arabidopsis, leaves contribute to the largest part of the aboveground biomass.
      In these organs, light is captured and converted into chemical energy, which
      plants use to grow and complete their life cycle. Leaves emerge as a small pool
      of cells at the vegetative shoot apical meristem and develop into planar, complex
      organs through different interconnected cellular events. Over the last decade,
      numerous phenotyping techniques have been developed to visualize and quantify
      leaf size and growth, leading to the identification of numerous genes that
      contribute to the final size of leaves. In this review, we will start at the
      Arabidopsis rosette level and gradually zoom in from a macroscopic view on leaf
      growth to a microscopic and molecular view. Along this journey, we describe
      different techniques that have been key to identify important events during leaf
      development and discuss approaches that will further help unraveling the complex
      cellular and molecular mechanisms that underlie leaf growth. 

PMID- 26217170
TI  - A pilot clinical trial on a Variable Automated Speed and Sensing Treadmill
      (VASST) for hemiparetic gait rehabilitation in stroke patients.
AB  - INTRODUCTION: Impairments in walking speed and capacity are common problems after
      stroke which may benefit from treadmill training. However, standard treadmills,
      are unable to adapt to the slower walking speeds of stroke survivors and are
      unable to automate training progression. This study tests a Variable Automated
      Speed and Sensing Treadmill (VASST) using a standard clinical protocol. VASST is
      a semi-automated treadmill with multiple sensors and micro controllers, including
      wireless control to reposition a fall-prevention harness, variable pre-programmed
      exercise parameters and laser beam foot sensors positioned on the belt to detect
      subject's foot positions. MATERIALS AND METHODS: An open-label study with
      assessor blinding was conducted in 10 community-dwelling chronic hemiplegic
      patients who could ambulate at least 0.1 m/s. Interventions included
      physiotherapist-supervised training on VASST for 60 min three times per week for
      4 weeks (total 12 h). Outcome measures of gait speed, quantity, balance, and
      adverse events were assessed at baseline, 2, 4, and 8 weeks. RESULTS: Ten
      subjects (8 males, mean age 55.5 years, 2.1 years post stroke) completed VASST
      training. Mean 10-m walk test speed was 0.69 m/s (SD = 0.29) and mean 6-min walk
      test distance was 178.3 m (84.0). After 4 weeks of training, 70% had significant
      positive gains in gait speed (0.06 m/s, SD = 0.08 m/s, P = 0.037); and 90%
      improved in walking distance. (54.3 m, SD = 30.9 m, P = 0.005). There were no
      adverse events. DISCUSSION AND CONCLUSION: This preliminary study demonstrates
      the initial feasibility and short-term efficacy of VASST for walking speed and
      distance for people with chronic post-stroke hemiplegia.

PMID- 26217171
TI  - Closed-loop stimulation of a delayed neural fields model of parkinsonian STN-GPe
      network: a theoretical and computational study.
AB  - Several disorders are related to pathological brain oscillations. In the case of
      Parkinson's disease, sustained low-frequency oscillations (especially in the beta
      band, 13-30 Hz) correlate with motor symptoms. It is still under debate whether
      these oscillations are the cause of parkinsonian motor symptoms. The development
      of techniques enabling selective disruption of these beta-oscillations could
      contribute to the understanding of the underlying mechanisms, and could be
      exploited for treatments. A particularly appealing technique is Deep Brain
      Stimulation (DBS). With clinical electrical DBS, electrical currents are
      delivered at high frequency to a region made of potentially heterogeneous neurons
      (the subthalamic nucleus (STN) in the case of Parkinson's disease). Even more
      appealing is DBS with optogenetics, which is until now a preclinical method using
      both gene transfer and deep brain light delivery and enabling neuromodulation at
      the scale of one given neural network. In this work, we rely on delayed neural
      fields models of STN and the external Globus Pallidus (GPe) to develop,
      theoretically validate and test in silico a closed-loop stimulation strategy to
      disrupt these sustained oscillations with optogenetics. First, we rely on tools
      from control theory to provide theoretical conditions under which sustained
      oscillations can be attenuated by a closed-loop stimulation proportional to the
      measured activity of STN. Second, based on this theoretical framework, we show
      numerically that the proposed closed-loop stimulation efficiently attenuates
      sustained oscillations, even in the case when the photosensitization effectively
      affects only 50% of STN neurons. We also show through simulations that
      oscillations disruption can be achieved when the same light source is used for
      the whole STN population. We finally test the robustness of the proposed strategy
      to possible acquisition and processing delays, as well as parameters uncertainty.

PMID- 26217173
TI  - Tunnel junction based memristors as artificial synapses.
AB  - We prepared magnesia, tantalum oxide, and barium titanate based tunnel junction
      structures and investigated their memristive properties. The low amplitudes of
      the resistance change in these types of junctions are the major obstacle for
      their use. Here, we increased the amplitude of the resistance change from 10% up
      to 100%. Utilizing the memristive properties, we looked into the use of the
      junction structures as artificial synapses. We observed analogs of long-term
      potentiation, long-term depression and spike-time dependent plasticity in these
      simple two terminal devices. Finally, we suggest a possible pathway of these
      devices toward their integration in neuromorphic systems for storing analog
      synaptic weights and supporting the implementation of biologically plausible
      learning mechanisms. 

PMID- 26217172
TI  - Marked effects of intracranial volume correction methods on sex differences in
      neuroanatomical structures: a HUNT MRI study.
AB  - To date, there is no consensus whether sexual dimorphism in the size of
      neuroanatomical structures exists, or if such differences are caused by choice of
      intracranial volume (ICV) correction method. When investigating volume
      differences in neuroanatomical structures, corrections for variation in ICV are
      used. Commonly applied methods are the ICV-proportions, ICV-residuals and ICV as
      a covariate of no interest, ANCOVA. However, these different methods give
      contradictory results with regard to presence of sex differences. Our aims were
      to investigate presence of sexual dimorphism in 18 neuroanatomical volumes
      unrelated to ICV-differences by using a large ICV-matched subsample of 304 men
      and women from the HUNT-MRI general population study, and further to demonstrate
      in the entire sample of 966 healthy subjects, which of the ICV-correction methods
      gave results similar to the ICV-matched subsample. In addition, sex-specific
      subsamples were created to investigate whether differences were an effect of head
      size or sex. Most sex differences were related to volume scaling with ICV,
      independent of sex. Sex differences were detected in a few structures; amygdala,
      cerebellar cortex, and 3rd ventricle were larger in men, but the effect sizes
      were small. The residuals and ANCOVA methods were most effective at removing the
      effects of ICV. The proportions method suffered from systematic errors due to
      lack of proportionality between ICV and neuroanatomical volumes, leading to
      systematic mis-assignment of structures as either larger or smaller than their
      actual size. Adding additional sexual dimorphic covariates to the ANCOVA gave
      opposite results of those obtained in the ICV-matched subsample or with the
      residuals method. The findings in the current study explain some of the
      considerable variation in the literature on sexual dimorphisms in neuroanatomical
      volumes. In conclusion, sex plays a minor role for neuroanatomical volume
      differences; most differences are related to ICV. 

PMID- 26217174
TI  - Telomere length is highly inherited and associated with hyperactivity-impulsivity
      in children with attention deficit/hyperactivity disorder.
AB  - Telomere length (TL) is highly heritable, and a shorter telomere at birth may
      increase the risk of age-related problems. Additionally, a shorter TL may
      represent a biomarker of chronic stress and has been associated with psychiatric
      disorders. However, no study has explored whether there is an association between
      TL and the symptoms of one of the most common neurodevelopmental disorders in
      childhood: Attention Deficit/Hyperactive Disorder (ADHD). We evaluated 61 (range,
      6-16 years) ADHD children and their parents between 2012 and 2014. TL was
      measured with a quantitative polymerase chain reaction method with telomere
      signal normalized to the signal from a single copy gene (36B4) to generate a T/S
      ratio. Family data was processed through a generalized estimated equations (GEE)
      model to determine the effect of parental TL on children TL. Inattentive and
      hyperactive-impulsive symptoms were also evaluated in relation to TL. For the
      first time, we found general heritability to be the major mechanism explaining
      interindividual TL variation in ADHD (father-child: 95% CI = 0.35/0.91, p <
      0.001; mother-child: 95% CI = 0.38/0.74, p < 0.001). The hyperactive-impulsive
      dimension of ADHD was related with children's TL (r = -339, p = 0.008) and
      maternal TL (r = -264, p = 0.047), but not with paternal TL (p > 0.05). The ADHD
      inattentive dimension was not significant associated with TL in this study (p >
      0.05). TL was shown to be a potential biomarker of the ADHD symptoms burden in
      families affected by this neurodevelopmental disorder. However, it is crucial
      that future studies investigating the rate of telomere attrition in relation to
      psychiatric problems to consider the strong determination of TL at birth by
      inheritance. 

PMID- 26217176
TI  - NMDA receptor GluN2A/GluN2B subunit ratio as synaptic trait of levodopa-induced
      dyskinesias: from experimental models to patients.
AB  - Levodopa-induced dyskinesias (LIDs) are major complications in the
      pharmacological management of Parkinson's disease (PD). Abnormal glutamatergic
      transmission in the striatum is considered a key factor in the development of
      LIDs. This work aims at: (i) characterizing N-methyl-D-aspartate (NMDA) receptor
      GluN2A/GluN2B subunit ratio as a common synaptic trait in rat and primate models
      of LIDs as well as in dyskinetic PD patients; and (ii) validating the potential
      therapeutic effect of a cell-permeable peptide (CPP) interfering with GluN2A
      synaptic localization on the dyskinetic behavior of these experimental models of
      LIDs. Here we demonstrate an altered ratio of synaptic GluN2A/GluN2B-containing
      NMDA receptors in the striatum of levodopa-treated dyskinetic rats and monkeys as
      well as in post-mortem tissue from dyskinetic PD patients. The modulation of
      synaptic NMDA receptor composition by a cell-permeable peptide interfering with
      GluN2A subunit interaction with the scaffolding protein postsynaptic density
      protein 95 (PSD-95) leads to a reduction in the dyskinetic motor behavior in the
      two animal models of LIDs. Our results indicate that targeting synaptic NMDA
      receptor subunit composition may represent an intriguing therapeutic approach
      aimed at ameliorating levodopa motor side effects. 

PMID- 26217175
TI  - Mechanochemical regulation of growth cone motility.
AB  - Neuronal growth cones are exquisite sensory-motor machines capable of transducing
      features contacted in their local extracellular environment into guided process
      extension during development. Extensive research has shown that chemical ligands
      activate cell surface receptors on growth cones leading to intracellular signals
      that direct cytoskeletal changes. However, the environment also provides
      mechanical support for growth cone adhesion and traction forces that stabilize
      leading edge protrusions. Interestingly, recent work suggests that both the
      mechanical properties of the environment and mechanical forces generated within
      growth cones influence axon guidance. In this review we discuss novel molecular
      mechanisms involved in growth cone force production and detection, and speculate
      how these processes may be necessary for the development of proper neuronal
      morphogenesis.

PMID- 26217177
TI  - Contra-Directional Expression of Serum Homocysteine and Uric Acid as Important
      Biomarkers of Multiple System Atrophy Severity: A Cross-Sectional Study.
AB  - HIGHLIGHTS: Serum Hcy was higher in MSA patients when compared to healthy
      subjects, particularly in male patients.Serum UA was lower in MSA patients when
      compared healthy subjects, particularly in male patients.Serum Hcy levels were
      significantly positively correlated with the severity of MSA.The ROC curve for
      the combination of Hcy and UA showed potential diagnostic value in discriminating
      MSA from healthy subjects. AIM: There is evidence suggesting that inflammatory
      responses play a critical role in the pathogenesis of multiple system atrophy
      (MSA). Whether inflammatory mediators can be used as reliable biomarkers to
      detect the severity and progression of MSA remains largely unknown. METHODS: We
      performed a cross-sectional study that included 47 patients with MSA and 50
      healthy age-matched controls. Serum levels of homocysteine (Hcy), uric acid (UA),
      and C-reactive protein (CRP) were measured. These levels positively correlated
      with the severity of MSA, based on both motor and non-motor symptoms. Several
      scales were used to rate the severity of MSA, including the Unified multiple
      system atrophy rating scale, Parkinson's disease sleep scale, Non-motor Symptoms
      Scale, the Schwab & England activities of daily living scale, Webster Scale,
      modified Hoehn and Yahr staging scale, and the Mini-Mental State Examination.
      Receiver operating characteristic (ROC) curves was applied to map the diagnostic
      accuracy of MSA against healthy subjects. RESULTS: Compared with healthy
      subjects, we found that serum Hcy was higher, UA was lower, and CRP levels were
      unchanged in MSA patients. These findings were especially prominent in male
      patients. No significant differences of serum Hcy and UA were observed between
      patients of MSA and PD. Interestingly, there was a significant correlation
      between Hcy levels and MSA severity such as movement dysfunction, declined
      cognition, and cardiovascular symptoms. Additionally, the ROC curve for the
      combination of Hcy and UA (AUC 0.736) showed potential diagnostic value in
      discriminating MSA from healthy subjects. CONCLUSION: Our findings suggest that
      the inflammatory mediators Hcy and UA may play important roles in the
      pathogenesis of MSA. The measurement of serum Hcy and UA levels could then be a
      useful tool to accurately distinguish MSA from healthy subjects.

PMID- 26217179
TI  - Active mechanistic target of rapamycin plays an ancillary rather than essential
      role in zebrafish CNS axon regeneration.
AB  - The developmental decrease of the intrinsic regenerative ability of the mammalian
      central nervous system (CNS) is associated with reduced activity of mechanistic
      target of rapamycin (mTOR) in mature neurons such as retinal ganglion cells
      (RGCs). While mTOR activity is further decreased upon axonal injury, maintenance
      of its pre-injury level, for instance by genetic deletion of the phosphatase and
      tensin homolog (PTEN), markedly promotes axon regeneration in mammals. The
      current study now addressed the question whether active mTOR might generally play
      a central role in axon regeneration by analyzing its requirement in regeneration
      competent zebrafish. Remarkably, regulation of mTOR activity after optic nerve
      injury in zebrafish is fundamentally different compared to mammals. Hardly any
      activity was detected in naive RGCs, whereas it was markedly increased upon
      axotomy in vivo as well as in dissociated cell cultures. After a short burst,
      mTOR activity was quickly attenuated, which is contrary to the requirements for
      axon regeneration in mammals. Surprisingly, mTOR activity was not essential for
      axonal growth per se, but correlated with cytokine- and PTEN inhibitor-induced
      neurite extension in vitro. Moreover, inhibition of mTOR using rapamycin
      significantly reduced axon regeneration in vivo and compromised functional
      recovery after optic nerve injury. Therefore, axotomy-induced mTOR activity is
      involved in CNS axon regeneration in zebrafish similar to mammals, although it
      plays an ancillary rather than essential role in this regeneration-competent
      species. 

PMID- 26217178
TI  - Mesenchymal stem cells secretome as a modulator of the neurogenic niche: basic
      insights and therapeutic opportunities.
AB  - Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) share few
      characteristics apart from self-renewal and multipotency. In fact, the neurogenic
      and osteogenic stem cell niches derive from two distinct embryonary structures;
      while the later originates from the mesoderm, as all the connective tissues do,
      the first derives from the ectoderm. Therefore, it is highly unlikely that stem
      cells isolated from one niche could form terminally differentiated cells from the
      other. Additionally, these two niches are associated to tissues/systems (e.g.,
      bone and central nervous system) that have markedly different needs and display
      diverse functions within the human body. Nevertheless they do share common
      features. For instance, the differentiation of both NSCs and MSCs is intimately
      associated with the bone morphogenetic protein family. Moreover, both NSCs and
      MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF),
      glial derived neurotrophic factor (GDNF), and brain derived neurotrophic factor
      (BDNF), among others. But it is not the features they share but the interaction
      between them that seem most important, and worth exploring; namely, it has
      already been shown that there are mutually beneficially effects when these cell
      types are co-cultured in vitro. In fact the use of MSCs, and their secretome,
      become a strong candidate to be used as a therapeutic tool for CNS applications,
      namely by triggering the endogenous proliferation and differentiation of neural
      progenitors, among other mechanisms. Quite interestingly it was recently revealed
      that MSCs could be found in the human brain, in the vicinity of capillaries. In
      the present review we highlight how MSCs and NSCs in the neurogenic niches
      interact. Furthermore, we propose directions on this field and explore the future
      therapeutic possibilities that may arise from the combination/interaction of MSCs
      and NSCs. 

PMID- 26217181
TI  - Testosterone-induced adult neurosphere growth is mediated by sexually-dimorphic
      aromatase expression.
AB  - We derived adult neural stem/progenitor cells (NSPCs) from the sub-ventricular
      zone of male and female mice to examine direct responses to principal sex
      hormones. In the presence of epidermal growth factor (EGF) and fibroblast growth
      factor-2 (FGF2) NSPCs of both sexes expressed nestin and sox2, and could be
      maintained as neurospheres without addition of any sex hormones. The reverse was
      not observed; neither testosterone (T), 17beta-estradiol (E2) nor progesterone
      (P4) was able to support neurosphere growth in the absence of EGF and FGF2. Ten
      nanomolar T, E2 or P4 induced nestin(+) cell proliferation within 20 min and
      enhanced neurosphere growth over 7 days irrespective of sex, which was abolished
      by Erk inhibition with 20 MUM U0126. Maintaining neurospheres with each sex
      hormone did not affect subsequent neuronal differentiation. However, 10 nM T, E2
      or P4 added during differentiation increased betaIII tubulin(+) neuron production
      with E2 being more potent compared to T and P4 in both sexes. Androgen receptor
      (AR) inhibition with 20 MUM flutamide but not aromatase inhibition with 10 MUM
      letrozole reduced basal and T-induced neurosphere growth in females, while only
      concurrent inhibition of AR and aromatase produced the same effect in males. This
      sex-specific effect was supported by higher aromatase expression in male
      neurospheres compared to females measured by Western blot and green fluorescent
      protein (GFP) reporter. Ten micromolar menadione induced oxidative stress,
      impaired neurosphere growth and up-regulated aromatase expression in both sexes.
      However, under oxidative stress letrozole significantly exacerbated impaired
      neurosphere growth in males only. While both E2 and T could prevent oxidative
      stress-induced growth reduction in both sexes, the effects of T were dependent on
      innate aromatase activity. We show for the first time that intrinsic androgen and
      estrogen signaling may impact the capacity of NSPCs to produce neural progenitors
      under pathological conditions of oxidative stress. 

PMID- 26217180
TI  - Ciliobrevins as tools for studying dynein motor function.
AB  - Dyneins are a small class of molecular motors that bind to microtubules and walk
      toward their minus ends. They are essential for the transport and distribution of
      organelles, signaling complexes and cytoskeletal elements. In addition dyneins
      generate forces on microtubule arrays that power the beating of cilia and
      flagella, cell division, migration and growth cone motility. Classical approaches
      to the study of dynein function in axons involve the depletion of dynein,
      expression of mutant/truncated forms of the motor, or interference with accessory
      subunits. By necessity, these approaches require prolonged time periods for the
      expression or manipulation of cellular dynein levels. With the discovery of the
      ciliobrevins, a class of cell permeable small molecule inhibitors of dynein, it
      is now possible to acutely disrupt dynein both globally and locally. In this
      review, we briefly summarize recent work using ciliobrevins to inhibit dynein and
      discuss the insights ciliobrevins have provided about dynein function in various
      cell types with a focus on neurons. We temper this with a discussion of the need
      for studies that will elucidate the mechanism of action of ciliobrevin and as
      well as the need for experiments to further analyze the specificity of
      ciliobreviens for dynein. Although much remains to be learned about ciliobrevins,
      these small molecules are proving themselves to be valuable novel tools to assess
      the cellular functions of dynein. 

PMID- 26217182
TI  - Regulated phosphorylation of the K-Cl cotransporter KCC3 is a molecular switch of
      intracellular potassium content and cell volume homeostasis.
AB  - The defense of cell volume against excessive shrinkage or swelling is a
      requirement for cell function and organismal survival. Cell swelling triggers a
      coordinated homeostatic response termed regulatory volume decrease (RVD),
      resulting in K(+) and Cl(-) efflux via activation of K(+) channels, volume
      regulated anion channels (VRACs), and the K(+)-Cl(-) cotransporters, including
      KCC3. Here, we show genetic alanine (Ala) substitution at threonines (Thr) 991
      and 1048 in the KCC3a isoform carboxyl-terminus, preventing inhibitory
      phosphorylation at these sites, not only significantly up-regulates KCC3a
      activity up to 25-fold in normally inhibitory isotonic conditions, but is also
      accompanied by reversal of activity of the related bumetanide-sensitive Na(+)
      K(+)-2Cl(-) cotransporter isoform 1 (NKCC1). This results in a rapid (<10 min)
      and significant (>90%) reduction in intracellular K(+) content (Ki) via both Cl
      dependent (KCC3a + NKCC1) and Cl-independent [DCPIB (VRAC inhibitor)-sensitive]
      pathways, which collectively renders cells less prone to acute swelling in
      hypotonic osmotic stress. Together, these data demonstrate the phosphorylation
      state of Thr991/Thr1048 in KCC3a encodes a potent switch of transporter activity,
      Ki homeostasis, and cell volume regulation, and reveal novel observations into
      the functional interaction among ion transport molecules involved in RVD. 

PMID- 26217184
TI  - Understanding the role of P2X7 in affective disorders-are glial cells the major
      players?
AB  - Pathophysiology associated with several psychiatric disorders has been linked to
      inflammatory biomarkers. This has generated a theory of major depressive
      disorders as an inflammatory disease. The idea of pro-inflammatory cytokines
      altering behavior is now well accepted however many questions remain. Microglia
      can produce a plethora of inflammatory cytokines and these cells appear to be
      critical in the link between inflammatory changes and depressive disorders.
      Microglia play a known role in sickness behavior which has many components of
      depressive-like behavior such as social withdrawal, sleep alterations, and
      anorexia. Numerous candidate genes have been identified for psychiatric disorders
      in the last decade. Single nucleotide polymorphisms (SNPs) in the human P2X7 gene
      have been linked to bipolar disorder, depression, and to the severity of
      depressive symptoms. P2X7 is a ligand-gated cation channel expressed on microglia
      with lower levels found on astrocytes and on some neuronal populations. In
      microglia P2X7 is a major regulator of pro-inflammatory cytokines of the
      interleukin-1 family. Genetic deletion of P2X7 in mice is protective for
      depressive behavior in addition to inflammatory responses. P2X7(-/-) mice have
      been shown to demonstrate anti-depressive-like behavior in forced swim and tail
      suspension behavioral tests and stressor-induced behavioral responses were
      blunted. Both neurochemical (norepinephrine, serotonin, and dopamine) and
      inflammatory changes have been observed in the brains of P2X7(-/-) mice. This
      review will discuss the recent evidence for involvement of P2X7 in the
      pathophysiology of depressive disorders and propose mechanisms by which altered
      signaling through this ion channel may affect the inflammatory state of the
      brain. 

PMID- 26217183
TI  - Physical biology of human brain development.
AB  - Neurodevelopment is a complex, dynamic process that involves a precisely
      orchestrated sequence of genetic, environmental, biochemical, and physical
      events. Developmental biology and genetics have shaped our understanding of the
      molecular and cellular mechanisms during neurodevelopment. Recent studies suggest
      that physical forces play a central role in translating these cellular mechanisms
      into the complex surface morphology of the human brain. However, the precise
      impact of neuronal differentiation, migration, and connection on the physical
      forces during cortical folding remains unknown. Here we review the cellular
      mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern
      selection, and evolution of shape. We revisit cortical folding as the instability
      problem of constrained differential growth in a multi-layered system. To identify
      the contributing factors of differential growth, we map out the timeline of
      neurodevelopment in humans and highlight the cellular events associated with
      extreme radial and tangential expansion. We demonstrate how computational
      modeling of differential growth can bridge the scales-from phenomena on the
      cellular level toward form and function on the organ level-to make quantitative,
      personalized predictions. Physics-based models can quantify cortical stresses,
      identify critical folding conditions, rationalize pattern selection, and predict
      gyral wavelengths and gyrification indices. We illustrate that physical forces
      can explain cortical malformations as emergent properties of developmental
      disorders. Combining biology and physics holds promise to advance our
      understanding of human brain development and enable early diagnostics of cortical
      malformations with the ultimate goal to improve treatment of neurodevelopmental
      disorders including epilepsy, autism spectrum disorders, and schizophrenia. 

PMID- 26217186
TI  - Editorial: Plasticity of GABAergic synapses.

PMID- 26217187
TI  - Corrigendum: Versatility of the complement system in neuroinflammation,
      neurodegeneration, and brain homeostasis.
AB  - [This corrects the article on p. 380 in vol. 8, PMID: 25426028.]. 

PMID- 26217185
TI  - Functional alterations of astrocytes in mental disorders: pharmacological
      significance as a drug target.
AB  - Astrocytes play an essential role in supporting brain functions in physiological
      and pathological states. Modulation of their pathophysiological responses have
      beneficial actions on nerve tissue injured by brain insults and neurodegenerative
      diseases, therefore astrocytes are recognized as promising targets for
      neuroprotective drugs. Recent investigations have identified several astrocytic
      mechanisms for modulating synaptic transmission and neural plasticity. These
      include altered expression of transporters for neurotransmitters, release of
      gliotransmitters and neurotrophic factors, and intercellular communication
      through gap junctions. Investigation of patients with mental disorders shows
      morphological and functional alterations in astrocytes. According to these
      observations, manipulation of astrocytic function by gene mutation and
      pharmacological tools reproduce mental disorder-like behavior in experimental
      animals. Some drugs clinically used for mental disorders affect astrocyte
      function. As experimental evidence shows their role in the pathogenesis of mental
      disorders, astrocytes have gained much attention as drug targets for mental
      disorders. In this paper, I review functional alterations of astrocytes in
      several mental disorders including schizophrenia, mood disorder, drug dependence,
      and neurodevelopmental disorders. The pharmacological significance of astrocytes
      in mental disorders is also discussed. 

PMID- 26217188
TI  - Commentary: Targeting LDH enzymes with a stiripentol analog to treat epilepsy.

PMID- 26217189
TI  - Inhibitory axons are targeted in hippocampal cell culture by anti-Caspr2
      autoantibodies associated with limbic encephalitis.
AB  - Contactin-associated protein-like 2 (Caspr2), also known as CNTNAP2, is a cell
      adhesion molecule that clusters voltage-gated potassium channels (Kv1.1/1.2) at
      the juxtaparanodes of myelinated axons and may regulate axonal excitability. As a
      component of the Kv1 complex, Caspr2 has been identified as a target in
      neuromyotonia and Morvan syndrome, but also in some cases of autoimmune limbic
      encephalitis (LE). How anti-Caspr2 autoimmunity is linked with the central
      neurological symptoms is still elusive. In the present study, using anti-Caspr2
      antibodies from seven patients affected by pure LE, we determined that IgGs in
      the cerebrospinal fluid of four out seven patients were selectively directed
      against the N-terminal Discoidin and LamininG1 modules of Caspr2. Using live
      immunolabeling of cultured hippocampal neurons, we determined that serum IgGs in
      all patients strongly targeted inhibitory interneurons. Caspr2 was highly
      detected on GAD65-positive axons that are surrounding the cell bodies and at the
      VGAT-positive inhibitory presynaptic contacts. Functional assays indicated that
      LE autoantibodies may induce alteration of Gephyrin clusters at inhibitory
      synaptic contacts. Next, we generated a Caspr2-Fc chimera to reveal Caspr2
      receptors on hippocampal neurons localized at the somato-dendritic compartment
      and post-synapse. Caspr2-Fc binding was strongly increased on TAG-1-transfected
      neurons and conversely, Caspr2-Fc did not bind hippocampal neurons from TAG-1
      deficient mice. Our data indicate that Caspr2 may participate as a cell
      recognition molecule in the dynamics of inhibitory networks. This study provides
      new insight into the potential pathogenic effect of anti-Caspr2 autoantibodies in
      central hyperexcitability that may be related with perturbation of inhibitory
      interneuron activity. 

PMID- 26217191
TI  - IFN gamma regulates proliferation and neuronal differentiation by STAT1 in adult
      SVZ niche.
AB  - The adult subventricular zone (SVZ) is the main neurogenic niche in normal adult
      brains of mice and rats. Interferon gamma (IFNgamma) has somewhat controversially
      been associated with SVZ progenitor proliferation and neurogenesis. The in vivo
      involvement of IFNgamma in the physiology of the adult SVZ niche is not fully
      understood and its intracellular mediators are unknown. Here we show that
      IFNgamma, through activation of its canonical signal transducer and activator of
      transcription 1 (STAT1) pathway, acts specifically on Nestin+ progenitors by
      decreasing both progenitor proliferation and the number of cycling cells. In
      addition, IFNgamma increases the number of neuroblasts generated without shifting
      glial fate determination. The final result is deficient recruitment of newborn
      neurons to the olfactory bulb (OB), indicating that IFNgamma-induced stimulation
      of neuronal differentiation does not compensate for its antiproliferative effect.
      We conclude that IFNgamma signaling via STAT1 in the SVZ acts dually as an
      antiproliferative and proneurogenic factor, and thereby regulates neurogenesis in
      normal adult brains. 

PMID- 26217190
TI  - Glia in the cytokine-mediated onset of depression: fine tuning the immune
      response.
AB  - Major depressive disorder (MDD) is a mood disorder of multifactorial origin
      affecting millions of people worldwide. The alarming estimated rates of
      prevalence and relapse make it a global public health concern. Moreover, the
      current setback of available antidepressants in the clinical setting is
      discouraging. Therefore, efforts to eradicate depression should be directed
      towards understanding the pathomechanisms involved in the hope of finding cost
      effective treatment alternatives. The pathophysiology of MDD comprises the
      breakdown of different pathways, including the hypothalamus-pituitary-adrenal
      (HPA) axis, the glutamatergic system, and monoaminergic neurotransmission,
      affecting cognition and emotional behavior. Inflammatory cytokines have been
      postulated to be the possible link and culprit in the disruption of these
      systems. In addition, evidence from different studies suggests that impairment of
      glial functions appears to be a major contributor as well. Thus, the intricate
      role between glia, namely microglia and astrocytes, and the central nervous
      system's (CNSs) immune response is briefly discussed, highlighting the kynurenine
      pathway as a pivotal player. Moreover, evaluations of different treatment
      strategies targeting the inflammatory response are considered. The immuno
      modulatory properties of vitamin D receptor (VDR) suggest that vitamin D is an
      attractive and plausible candidate in spite of controversial findings. Further
      research investigating the role of VDR in mood disorders is warranted. 

PMID- 26217192
TI  - Subthalamic deep brain stimulation reduces pathological information transmission
      to the thalamus in a rat model of parkinsonism.
AB  - The degeneration of dopaminergic neurons in the substantia nigra pars compacta
      leads to parkinsonian motor symptoms via changes in electrophysiological activity
      throughout the basal ganglia. High-frequency deep brain stimulation (DBS)
      partially treats these symptoms, but the mechanisms are unclear. We hypothesize
      that motor symptoms of Parkinson's disease (PD) are associated with increased
      information transmission from basal ganglia output neurons to motor thalamus
      input neurons and that therapeutic DBS of the subthalamic nucleus (STN) treats
      these symptoms by reducing this extraneous information transmission. We tested
      these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of
      hemiparkinsonism. Information transfer between basal ganglia output neurons and
      motor thalamus input neurons increased in both the orthodromic and antidromic
      directions with hemiparkinsonian (hPD) onset, and these changes were reversed by
      behaviorally therapeutic STN-DBS. Omnidirectional information increases in the
      parkinsonian state underscore the detrimental nature of that pathological
      information and suggest a loss of information channel independence. Therapeutic
      STN-DBS reduced that pathological information, suggesting an effective increase
      in the number of independent information channels. We interpret these data with a
      model in which pathological information and fewer information channels diminishes
      the scope of possible motor activities, driving parkinsonian symptoms. In this
      model, STN-DBS restores information-channel independence by eliminating or
      masking the parkinsonism-associated information, and thus enlarges the scope of
      possible motor activities, alleviating parkinsonian symptoms. 

PMID- 26217193
TI  - A common evolutionary origin for the ON- and OFF-edge motion detection pathways
      of the Drosophila visual system.
AB  - Synaptic circuits for identified behaviors in the Drosophila brain have typically
      been considered from either a developmental or functional perspective without
      reference to how the circuits might have been inherited from ancestral forms. For
      example, two candidate pathways for ON- and OFF-edge motion detection in the
      visual system act via circuits that use respectively either T4 or T5, two cell
      types of the fourth neuropil, or lobula plate (LOP), that exhibit narrow-field
      direction-selective responses and provide input to wide-field tangential neurons.
      T4 or T5 both have four subtypes that terminate one each in the four strata of
      the LOP. Representatives are reported in a wide range of Diptera, and both cell
      types exhibit various similarities in: (1) the morphology of their dendritic
      arbors; (2) their four morphological and functional subtypes; (3) their
      cholinergic profile in Drosophila; (4) their input from the pathways of L3 cells
      in the first neuropil, or lamina (LA), and by one of a pair of LA cells, L1 (to
      the T4 pathway) and L2 (to the T5 pathway); and (5) their innervation by a
      single, wide-field contralateral tangential neuron from the central brain.
      Progenitors of both also express the gene atonal early in their proliferation
      from the inner anlage of the developing optic lobe, being alone among many other
      cell type progeny to do so. Yet T4 receives input in the second neuropil, or
      medulla (ME), and T5 in the third neuropil or lobula (LO). Here we suggest that
      these two cell types were originally one, that their ancestral cell population
      duplicated and split to innervate separate ME and LO neuropils, and that a fiber
      crossing-the internal chiasma-arose between the two neuropils. The split most
      plausibly occurred, we suggest, with the formation of the LO as a new neuropil
      that formed when it separated from its ancestral neuropil to leave the ME,
      suggesting additionally that ME input neurons to T4 and T5 may also have had a
      common origin. 

PMID- 26217194
TI  - Emergence of spatiotemporal invariance in large neuronal ensembles in rat barrel
      cortex.
AB  - Invariant sensory coding is the robust coding of some sensory information (e.g.,
      stimulus type) despite major changes in other sensory parameters (e.g., stimulus
      strength). The contribution of large populations of neurons (ensembles) to
      invariant sensory coding is not well understood, but could offer distinct
      advantages over invariance in single cell receptive fields. To test invariant
      sensory coding in neuronal ensembles evoked by single whisker stimulation as
      early as primary sensory cortex, we recorded detailed spatiotemporal movies of
      evoked ensemble activity through the depth of rat barrel cortex using
      microelectrode arrays. We found that an emergent property of whisker evoked
      ensemble activity, its spatiotemporal profile, was notably invariant across major
      changes in stimulus amplitude (up to >200-fold). Such ensemble-based invariance
      was found for single whisker stimulation as well as for the integrated profile of
      activity evoked by the more naturalistic stimulation of the entire whisker array.
      Further, the integrated profile of whisker array evoked ensemble activity and its
      invariance to stimulus amplitude shares striking similarities to "funneled"
      tactile perception in humans. We therefore suggest that ensemble-based invariance
      could provide a robust neurobiological substrate for invariant sensory coding and
      integration at an early stage of cortical sensory processing already in primary
      sensory cortex. 

PMID- 26217196
TI  - Pio del Rio Hortega and the discovery of the oligodendrocytes.
AB  - Pio del Rio Hortega (1882-1945) discovered microglia and oligodendrocytes (OLGs),
      and after Ramon y Cajal, was the most prominent figure of the Spanish school of
      neurology. He began his scientific career with Nicolas Achucarro from whom he
      learned the use of metallic impregnation techniques suitable to study non
      neuronal cells. Later on, he joined Cajal's laboratory. and Subsequently, he
      created his own group, where he continued to develop other innovative
      modifications of silver staining methods that revolutionized the study of glial
      cells a century ago. He was also interested in neuropathology and became a
      leading authority on Central Nervous System (CNS) tumors. In parallel to this
      clinical activity, del Rio Hortega rendered the first systematic description of a
      major polymorphism present in a subtype of macroglial cells that he named as
      oligodendroglia and later OLGs. He established their ectodermal origin and
      suggested that they built the myelin sheath of CNS axons, just as Schwann cells
      did in the periphery. Notably, he also suggested the trophic role of OLGs for
      neuronal functionality, an idea that has been substantiated in the last few
      years. Del Rio Hortega became internationally recognized and established an
      important neurohistological school with outstanding pupils from Spain and abroad,
      which nearly disappeared after his exile due to the Spanish civil war. Yet, the
      difficulty of metal impregnation methods and their variability in results,
      delayed for some decades the confirmation of his great insights into
      oligodendrocyte biology until the development of electron microscopy and
      immunohistochemistry. This review aims at summarizing the pioneer and essential
      contributions of del Rio Hortega to the current knowledge of oligodendrocyte
      structure and function, and to provide a hint of the scientific personality of
      this extraordinary and insufficiently recognized man. 

PMID- 26217195
TI  - Oxidative stress and Parkinson's disease.
AB  - Parkinson disease (PD) is a chronic, progressive neurological disease that is
      associated with a loss of dopaminergic neurons in the substantia nigra pars
      compacta of the brain. The molecular mechanisms underlying the loss of these
      neurons still remain elusive. Oxidative stress is thought to play an important
      role in dopaminergic neurotoxicity. Complex I deficiencies of the respiratory
      chain account for the majority of unfavorable neuronal degeneration in PD.
      Environmental factors, such as neurotoxins, pesticides, insecticides, dopamine
      (DA) itself, and genetic mutations in PD-associated proteins contribute to
      mitochondrial dysfunction which precedes reactive oxygen species formation. In
      this mini review, we give an update of the classical pathways involving these
      mechanisms of neurodegeneration, the biochemical and molecular events that
      mediate or regulate DA neuronal vulnerability, and the role of PD-related gene
      products in modulating cellular responses to oxidative stress in the course of
      the neurodegenerative process. 

PMID- 26217197
TI  - Individual predictors of sensorimotor adaptability.
AB  - There are large individual variations in strategies and rates of sensorimotor
      adaptation to spaceflight. This is seen in both the magnitude of performance
      disruptions when crewmembers are first exposed to microgravity, and in the rate
      of re-adaptation when they return to Earth's gravitational environment.
      Understanding the sources of this variation can lead to a better understanding of
      the processes underlying adaptation, as well as provide insight into potential
      routes for facilitating performance of "slow adapters". Here we review the
      literature on brain, behavioral, and genetic predictors of motor learning,
      recovery of motor function following neural insult, and sensorimotor adaptation.
      For example, recent studies have identified specific genetic polymorphisms that
      are associated with faster adaptation on manual joystick tasks and faster
      recovery of function following a stroke. Moreover, the extent of recruitment of
      specific brain regions during learning and adaptation has been shown to be
      predictive of the magnitude of subsequent learning. We close with suggestions for
      forward work aimed at identifying predictors of spaceflight adaptation success.
      Identification of "slow adapters" prior to spaceflight exposure would allow for
      more targeted preflight training and/or provision of booster training and
      adaptation adjuncts during spaceflight. 

PMID- 26217198
TI  - Memory bias in the temporal bisection point.
AB  - The ability to time intervals confers organisms, including humans, with many
      remarkable capabilities. A common method for studying interval timing is
      classification, in which a subject must indicate whether a given probe duration
      is nearer a previously learned short or long reference interval. This task is
      designed to reveal the probe duration that is equally likely to be labeled as
      short or long, known as the temporal bisection point. Studies have found that
      this bisection point is influenced by a variety of factors including the ratio of
      the target intervals, the spacing of the probe durations, the modalities of the
      stimuli, the attentional load, and the inter-trial duration. While several of
      these factors are thought to be mediated by memory effects, the prototypical
      classification task affords no opportunity to measure these memory effects
      directly. Here, we present a novel bisection task, termed the "Bisection by
      Classification and Production" (BiCaP) task, in which classification trials are
      interleaved with trials in which subjects must produce either the short or long
      referents or their midpoint. Using this method, we found a significant
      correlation between the means of the remembered referents and the bisection
      points for both classification and production trials. We then cross-validated the
      bisection points for production and classification trials by showing that they
      were not statistically differentiable. In addition to these population-level
      effects, we found within-subject evidence for co-variation across a session
      between the production bisection points and the means of the remembered
      referents. Finally, by using two sets of referent durations, we showed that only
      memory bias-corrected measures were consistent with a previously reported effect
      in which the ratio of the referents affects the location of the bisection point.
      These results suggest that memory effects should be considered in temporal tasks.

PMID- 26217199
TI  - Crossmodal semantic congruence can affect visuo-spatial processing and activity
      of the fronto-parietal attention networks.
AB  - Previous studies have shown that multisensory stimuli can contribute to attention
      control. Here we investigate whether irrelevant audio-visual stimuli can affect
      the processing of subsequent visual targets, in the absence of any direct bottom
      up signals generated by low-level sensory changes and any goal-related
      associations between the multisensory stimuli and the visual targets. Each trial
      included two pictures (cat/dog), one in each visual hemifield, and a central
      sound that was semantically congruent with one of the two pictures (i.e., either
      "meow" or "woof" sound). These irrelevant audio-visual stimuli were followed by a
      visual target that appeared either where the congruent or the incongruent picture
      had been presented (valid/invalid trials). The visual target was a Gabor patch
      requiring an orientation discrimination judgment, allowing us to uncouple the
      visual task from the audio-visual stimuli. Behaviourally we found lower
      performance for invalid than valid trials, but only when the task demands were
      high (Gabor target presented together with a Gabor distractor vs. Gabor target
      alone). The fMRI analyses revealed greater activity for invalid than for valid
      trials in the dorsal and the ventral fronto-parietal attention networks. The
      dorsal network was recruited irrespective of task demands, while the ventral
      network was recruited only when task demands were high and target discrimination
      required additional top-down control. We propose that crossmodal semantic
      congruence generates a processing bias associated with the location of congruent
      picture, and that the presentation of the visual target on the opposite side
      required updating these processing priorities. We relate the activation of the
      attention networks to these updating operations. We conclude that the fronto
      parietal networks mediate the influence of crossmodal semantic congruence on
      visuo-spatial processing, even in the absence of any low-level sensory cue and
      any goal-driven task associations. 

PMID- 26217200
TI  - Avoidance expression in rats as a function of signal-shock interval: strain and
      sex differences.
AB  - Inbred Wistar Kyoto (WKY) rats express inhibited temperament, increased
      sensitivity to stress, and exaggerated expressions of avoidance. A long-standing
      observation for lever press escape/avoidance learning in rats is the duration of
      the warning signal (WS) determines whether avoidance is expressed over escape.
      Outbred female Sprague-Dawley (SD) rats trained with a 10-s WS efficiently
      escaped, but failed to exhibit avoidance; avoidance was exhibited to a high
      degree with WSs longer than 20-s. We examined this longstanding WS duration
      function and extended it to male SD and male and female WKY rats. A cross-over
      design with two WS durations (10 or 60 s) was employed. Rats were trained (20
      trials/session) in four phases: acquisition (10 sessions), extinction (10
      sessions), re-acquisition (8 sessions) and re-extinction (8 sessions). Consistent
      with the literature, female and male SD rats failed to express avoidance to an
      appreciable degree with a 10-s WS. When these rats were switched to a 60-s WS,
      performance levels in the initial session of training resembled the peak
      performance of rats trained with a 60-s WS. Therefore, the avoidance relationship
      was acquired, but not expressed at 10-s WS. Further, poor avoidance at 10-s does
      not adversely affect expression at 60-s. Failure to express avoidance with a 10-s
      WS likely reflects contrasting reinforcement value of avoidance, not a reduction
      in the amount of time available to respond or competing responses. In contrast,
      WKY rats exhibited robust avoidance with a 10-s WS, which was most apparent in
      female WKY rats. Exaggerated expression of avoidances by WKY rats, especially
      female rats, further confirms this inbred strain as a model of anxiety
      vulnerability. 

PMID- 26217202
TI  - BDNF Val(66)Met and 5-HTTLPR Genotype are Each Associated with Visual Scanning
      Patterns of Faces in Young Children.
AB  - Previous studies have documented both neuroplasticity-related BDNF Val(66)Met and
      emotion regulation-related 5-HTTLPR polymorphisms as genetic variants that
      contribute to the processing of emotions from faces. More specifically, research
      has shown the BDNF Met allele and the 5-HTTLPR Short allele to be associated with
      mechanisms of negative affectivity that relate to susceptibility for
      psychopathology. We examined visual scanning pathways in response to angry,
      happy, and neutral faces in relation to BDNF Val(66)Met and 5-HTTLPR genotyping
      in 49 children aged 4-7 years. Analyses revealed that variations in the visual
      processing of facial expressions of anger interacted with BDNF Val(66)Met
      genotype, such that children who carried at least one low neuroplasticity Met
      allele exhibited a vigilance-avoidance pattern of visual scanning compared to
      homozygotes for the high neuroplasticity Val allele. In a separate investigation
      of eye gaze towards the eye versus mouth regions of neutral faces, we observed
      that short allele 5-HTTLPR carriers exhibited reduced looking at the eye region
      compared with those with the higher serotonin uptake Long allele. Together, these
      findings suggest that genetic mechanisms early in life may influence the
      establishment of patterns of visual scanning of environmental stressors, which in
      conjunction with other factors such as negative life events, may lead to
      psychological difficulties and disorders in the later adolescent and adult years.

PMID- 26217201
TI  - Neonatal handling decreases unconditioned anxiety, conditioned fear, and improves
      two-way avoidance acquisition: a study with the inbred Roman high (RHA-I)- and
      low-avoidance (RLA-I) rats of both sexes.
AB  - The present study evaluated the long-lasting effects of neonatal handling (NH;
      administered during the first 21 days of life) on unlearned and learned anxiety
      related responses in inbred Roman High- (RHA-I) and Low-avoidance (RLA-I) rats.
      To this aim, untreated and neonatally-handled RHA-I and RLA-I rats of both sexes
      were tested in the following tests/tasks: a novel object exploration (NOE) test,
      the elevated zero maze (ZM) test, a "baseline acoustic startle" (BAS) test, a
      "context-conditioned fear" (CCF) test and the acquisition of two-way active
      shuttle box-avoidance (SHAV). RLA-I rats showed higher unconditioned (novel
      object exploration test -"NOE"-, elevated zero maze test -"ZM"-, BAS), and
      conditioned (CCF, SHAV) anxiety. NH increased exploration of the novel object in
      the NOE test as well as exploration of the open sections of the ZM test in both
      rat strains and sexes, although the effects were relatively more marked in the
      (high anxious) RLA-I strain and in females. NH did not affect BAS, but reduced
      CCF in both strains and sexes, and improved shuttle box avoidance acquisition
      especially in RLA-I (and particularly in females) and in female RHA-I rats. These
      are completely novel findings, which indicate that even some genetically-based
      anxiety/fear-related phenotypes can be significantly modulated by previous
      environmental experiences such as the NH manipulation. 

PMID- 26217203
TI  - Dissociation between mental fatigue and motivational state during prolonged
      mental activity.
AB  - Mental fatigue (MF) is commonly observed following prolonged cognitive activity
      and can have major repercussions on the daily life of patients as well as healthy
      individuals. Despite its important impact, the cognitive processes involved in MF
      remain largely unknown. An influential hypothesis states that MF does not arise
      from a disruption of overused neural processes but, rather, is caused by a
      progressive decrease in motivation-related task engagement. Here, to test this
      hypothesis, we measured various neural, autonomic, psychometric and behavioral
      signatures of MF and motivation (EEG, ECG, pupil size, eye blinks, Skin
      conductance responses (SCRs), questionnaires and performance in a working memory
      (WM) task) in healthy volunteers, while MF was induced by Sudoku tasks performed
      for 120 min. Moreover extrinsic motivation was manipulated by using different
      levels of monetary reward. We found that, during the course of the experiment,
      the participants' subjective feeling of fatigue increased and their performance
      worsened while their blink rate and heart rate variability (HRV) increased.
      Conversely, reward-induced EEG, pupillometric and skin conductance signal
      changes, regarded as indicators of task engagement, remained constant during the
      experiment, and failed to correlate with the indices of MF. In addition, MF did
      not affect a simple reaction time task, despite the strong influence of extrinsic
      motivation on this task. Finally, alterations of the motivational state through
      monetary incentives failed to compensate the effects of MF. These findings
      indicate that MF in healthy subjects is not caused by an alteration of task
      engagement but is likely to be the consequence of a decrease in the efficiency,
      or availability, of cognitive resources. 

PMID- 26217204
TI  - Behavioral and molecular processing of visceral pain in the brain of mice: impact
      of colitis and psychological stress.
AB  - Gastrointestinal disorders with abdominal pain are associated with central
      sensitization and psychopathologies that are often exacerbated by stress. Here we
      investigated the impact of colitis induced by dextran sulfate sodium (DSS) and
      repeated water avoidance stress (WAS) on spontaneous and nociception-related
      behavior and molecular signaling in the mouse brain. DSS increased the mechanical
      pain sensitivity of the abdominal skin while both WAS and DSS enhanced the
      mechanical and thermal pain sensitivity of the plantar skin. These manifestations
      of central sensitization were associated with augmented c-Fos expression in
      spinal cord, thalamus, hypothalamus, amygdala and prefrontal cortex. While WAS
      stimulated phosphorylation of mitogen-activated protein kinase (MAPK) p42/44, DSS
      activated another signaling pathway, both of which converged on c-Fos. The DSS-
      and WAS-induced hyperalgesia in the abdominal and plantar skin and c-Fos
      expression in the brain disappeared when the mice were subjected to WAS+DSS
      treatment. Intrarectal allyl isothiocyanate (AITC) evoked aversive behavior
      (freezing, reduction of locomotion and exploration) in association with p42/44
      MAPK and c-Fos activation in spinal cord and brain. These effects were inhibited
      by morphine, which attests to their relationship with nociception. DSS and WAS
      exerted opposite effects on AITC-evoked p42/44 MAPK and c-Fos activation, which
      indicates that these transduction pathways subserve different aspects of visceral
      pain processing in the brain. In summary, behavioral perturbations caused by
      colitis and psychological stress are associated with distinct alterations in
      cerebral signaling. These findings provide novel perspectives on central
      sensitization and the sensory and emotional processing of visceral pain stimuli
      in the brain. 

PMID- 26217205
TI  - The role of the amygdala in the perception of positive emotions: an "intensity
      detector".
AB  - The specific role of the amygdala remains controversial even though the
      development of functional imaging techniques has established its implication in
      the emotional process. The aim of this study was to highlight the sensitivity of
      the amygdala to emotional intensity (arousal). We conducted an analysis of the
      modulation of amygdala activation according to variation in emotional intensity
      via an fMRI event-related protocol. Monitoring of electrodermal activity, a
      marker of psychophysiological emotional perception and a reflection of the
      activation of the autonomic nervous system, was carried out concurrently.
      Eighteen subjects (10 men; aged from 22 to 29 years) looked at emotionally
      positive photographs. We demonstrated that the left and right amygdalae were
      sensitive to changes in emotional intensity, activating more in response to
      stimuli with higher intensity. Furthermore, electrodermal responses were more
      frequent for the most intense stimuli, demonstrating the concomitant activation
      of the autonomic nervous system. These results highlight the sensitivity of the
      amygdala to the intensity of positively valenced visual stimuli, and in
      conjunction with results in the literature on negative emotions, reinforce the
      role of the amygdala in the perception of intensity. 

PMID- 26217206
TI  - Nxf7 deficiency impairs social exploration and spatio-cognitive abilities as well
      as hippocampal synaptic plasticity in mice.
AB  - Nuclear RNA export factors (NXF) are conserved in all metazoans and are deemed
      essential for shuttling RNA across the nuclear envelope and other post
      transcriptional processes (such as mRNA metabolism, storage and stability).
      Disruption of human NXF5 has been implicated in intellectual and psychosocial
      disabilities. In the present report, we use recently described Nxf7 knockout (KO)
      mice as an experimental model to analyze in detail the behavioral consequences of
      clinical NXF5 deficiency. We examined male Nxf7 KO mice using an extended
      cognitive and behavioral test battery, and recorded extracellular field
      potentials in the hippocampal CA1 region. We observed various cognitive and
      behavioral changes including alterations in social exploration, impaired spatial
      learning and spatio-cognitive abilities. We also defined a new experimental
      paradigm to discriminate search strategies in Morris water maze and showed
      significant differences between Nxf7 KO and control animals. Furthermore, while
      we observed no difference in a nose poke suppression in an conditioned emotional
      response (CER) protocol, Nxf7 KO mice were impaired in discriminating between
      differentially reinforced cues in an auditory fear conditioning protocol. This
      distinct neurocognitive phenotype was accompanied by impaired hippocampal Long
      term potentiation (LTP), while long-term depression (LTD) was not affected by
      Nxf7 deficiency. Our data demonstrate that disruption of murine Nxf7 leads to
      behavioral phenotypes that may relate to the intellectual and social deficits in
      patients with NXF5 deficiency. 

PMID- 26217207
TI  - Spontaneous object recognition: a promising approach to the comparative study of
      memory.
AB  - Spontaneous recognition of a novel object is a popular measure of exploratory
      behavior, perception and recognition memory in rodent models. Because of its
      relative simplicity and speed of testing, the variety of stimuli that can be
      used, and its ecological validity across species, it is also an attractive task
      for comparative research. To date, variants of this test have been used with
      vertebrate and invertebrate species, but the methods have seldom been
      sufficiently standardized to allow cross-species comparison. Here, we review the
      methods necessary for the study of novel object recognition in mammalian and non
      mammalian models, as well as the results of these experiments. Critical to the
      use of this test is an understanding of the organism's initial response to a
      novel object, the modulation of exploration by context, and species differences
      in object perception and exploratory behaviors. We argue that with appropriate
      consideration of species differences in perception, object affordances, and
      natural exploratory behaviors, the spontaneous object recognition test can be a
      valid and versatile tool for translational research with non-mammalian models. 

PMID- 26217208
TI  - Differential Effects of Parietal and Cerebellar Stroke in Response to Object
      Location Perturbation.
AB  - BACKGROUND: The differential contributions of the cerebellum and parietal lobe to
      coordination between hand transport and hand shaping to an object have not been
      clearly identified. OBJECTIVE: To contrast impairments in reach-to-grasp
      coordination, in response to object location perturbation, in patients with right
      parietal and cerebellar lesions, in order to further elucidate the role of each
      area in reach-to-grasp coordination. METHOD: A two-factor design with one between
      subject factor (right parietal stroke; cerebellar stroke; controls) and one
      within subject factor (presence or absence of object location perturbation)
      examined correction processes used to maintain coordination between transport-to
      grasp in the presence of perturbation. Sixteen chronic stroke participants (eight
      with right parietal lesions and eight with cerebellar lesions) were matched in
      age (mean = 61 years; standard deviation = 12) and hand dominance with 16 healthy
      controls. Hand and arm movements were recorded during unperturbed baseline trials
      (10) and unpredictable trials (60) in which the target was displaced to the left
      (10) or right (10) or remained fixed (40). RESULTS: Cerebellar patients had a
      slowed response to perturbation with anticipatory hand opening, an increased
      number of aperture peaks and disruption to temporal coordination, and greater
      variability. Parietal participants also exhibited slowed movements, with
      increased number of aperture peaks, but in addition, increased the number of
      velocity peaks and had a longer wrist path trajectory due to difficulties
      planning the new transport goal and thus relying more on feedback control.
      CONCLUSION: Patients with parietal or cerebellar lesions showed some similar and
      some contrasting deficits. The cerebellum was more dominant in controlling
      temporal coupling between transport and grasp components, and the parietal area
      was more concerned with using sensation to relate arm and hand state to target
      position.

PMID- 26217209
TI  - Mixed effectiveness of rTMS and retraining in the treatment of focal hand
      dystonia.
AB  - Though the pathophysiology of dystonia remains uncertain, two primary factors
      implicated in the development of dystonic symptoms are excessive cortical
      excitability and impaired sensorimotor processing. The aim of this study was to
      determine the functional efficacy of an intervention combining repetitive
      transcranial magnetic stimulation (rTMS) and sensorimotor retraining. A
      randomized, single-subject, multiple baseline design with crossover was used to
      examine participants with focal hand dystonia (FHD) (n = 9). INTERVENTION: 5 days
      rTMS + sensorimotor retraining (SMR) vs. Five days rTMS + control therapy (CTL)
      (which included stretching and massage). The rTMS was applied to the premotor
      cortex at 1 Hz at 80% resting motor threshold for 1200 pulses. For sensorimotor
      retraining, a subset of the Learning-based Sensorimotor Training program was
      followed. Each session in both groups consisted of rTMS followed immediately by
      30 min of the therapy intervention (SMR or CTL). Contrary to our hypothesis,
      group analyses revealed no additional benefit from the SMR training vs. CTL. When
      analyzed across group however, there was significant improvement from the first
      baseline assessment in several measures, including tests of sensory ability and
      self-rated changes. The patient rated improvements were accompanied by a moderate
      effect size suggesting clinical meaningfulness. These results provide
      encouragement for further investigation of rTMS in FHD with a need to optimize a
      secondary intervention and determine likely responders vs. non-responders.

PMID- 26217210
TI  - Dissociation of category-learning systems via brain potentials.
AB  - Behavioral, neuropsychological, and neuroimaging evidence has suggested that
      categories can often be learned via either an explicit rule-based (RB) mechanism
      critically dependent on medial temporal and prefrontal brain regions, or via an
      implicit information-integration (II) mechanism relying on the basal ganglia. In
      this study, participants viewed sine-wave gratings (Gabor patches) that varied on
      two dimensions and learned to categorize them via trial-by-trial feedback. Two
      different stimulus distributions were used; one was intended to encourage an
      explicit RB process and the other an implicit II process. We monitored brain
      activity with scalp electroencephalography (EEG) while each participant: (1)
      passively observed stimuli represented of both distributions; (2) categorized
      stimuli from one distribution, and, 1 week later; (3) categorized stimuli from
      the other distribution. Categorization accuracy was similar for the two
      distributions. Subtractions of Event-Related Potentials (ERPs) for correct and
      incorrect trials were used to identify neural differences in RB and II
      categorization processes. We identified an occipital brain potential that was
      differentially modulated by categorization condition accuracy at an early latency
      (150-250 ms), likely reflecting the degree of holistic processing. A stimulus
      locked Late Positive Complex (LPC) associated with explicit memory updating was
      modulated by accuracy in the RB, but not the II task. Likewise, a feedback-locked
      P300 ERP associated with expectancy was correlated with performance only in the
      RB, but not the II condition. These results provide additional evidence for
      distinct brain mechanisms supporting RB vs. implicit II category learning and
      use. 

PMID- 26217211
TI  - Midline Body Actions and Leftward Spatial "Aiming" in Patients with Spatial
      Neglect.
AB  - Spatial motor-intentional "Aiming" bias is a dysfunction in initiation/execution
      of motor-intentional behavior, resulting in hypokinetic and hypometric leftward
      movements. Aiming bias may contribute to posture, balance, and movement problems
      and uniquely account for disability in post-stroke spatial neglect. Body movement
      may modify and even worsen Aiming errors, but therapy techniques, such as visual
      scanning training, do not take this into account. Here, we evaluated (1) whether
      instructing neglect patients to move midline body parts improves their ability to
      explore left space and (2) whether this has a different impact on different
      patients. A 68-year-old woman with spatial neglect after a right basal ganglia
      infarct had difficulty orienting to and identifying left-sided objects. She was
      prompted with four instructions: "look to the left," "point with your nose to the
      left," "point with your [right] hand to the left," and "stick out your tongue and
      point it to the left." She oriented leftward dramatically better when pointing
      with the tongue/nose, than she did when pointing with the hand. We then tested
      nine more consecutive patients with spatial neglect using the same instructions.
      Only four of them made any orienting errors. Only one patient made >50% errors
      when pointing with the hand, and she did not benefit from pointing with the
      tongue/nose. We observed that pointing with the tongue could facilitate left
      sided orientation in a stroke survivor with spatial neglect. If midline
      structures are represented more bilaterally, they may be less affected by Aiming
      bias. Alternatively, moving the body midline may be more permissive for leftward
      orienting than moving right body parts. We were not able to replicate this effect
      in another patient; we suspect that the magnitude of this effect may depend upon
      the degree to which patients have directional akinesia, spatial Where deficits,
      or cerebellar/frontal cortical lesions. Future research could examine these
      hypotheses. 

PMID- 26217212
TI  - Cognitive control of conscious error awareness: error awareness and error
      positivity (Pe) amplitude in moderate-to-severe traumatic brain injury (TBI).
AB  - Poor awareness has been linked to worse recovery and rehabilitation outcomes
      following moderate-to-severe traumatic brain injury (M/S TBI). The error
      positivity (Pe) component of the event-related potential (ERP) is linked to error
      awareness and cognitive control. Participants included 37 neurologically healthy
      controls and 24 individuals with M/S TBI who completed a brief neuropsychological
      battery and the error awareness task (EAT), a modified Stroop go/no-go task that
      elicits aware and unaware errors. Analyses compared between-group no-go accuracy
      (including accuracy between the first and second halves of the task to measure
      attention and fatigue), error awareness performance, and Pe amplitude by level of
      awareness. The M/S TBI group decreased in accuracy and maintained error awareness
      over time; control participants improved both accuracy and error awareness during
      the course of the task. Pe amplitude was larger for aware than unaware errors for
      both groups; however, consistent with previous research on the Pe and TBI, there
      were no significant between-group differences for Pe amplitudes. Findings suggest
      possible attention difficulties and low improvement of performance over time may
      influence specific aspects of error awareness in M/S TBI. 

PMID- 26217213
TI  - Task-discriminative space-by-time factorization of muscle activity.
AB  - Movement generation has been hypothesized to rely on a modular organization of
      muscle activity. Crucial to this hypothesis is the ability to perform reliably a
      variety of motor tasks by recruiting a limited set of modules and combining them
      in a task-dependent manner. Thus far, existing algorithms that extract putative
      modules of muscle activations, such as Non-negative Matrix Factorization (NMF),
      identify modular decompositions that maximize the reconstruction of the recorded
      EMG data. Typically, the functional role of the decompositions, i.e., task
      accomplishment, is only assessed a posteriori. However, as motor actions are
      defined in task space, we suggest that motor modules should be computed in task
      space too. In this study, we propose a new module extraction algorithm, named
      DsNM3F, that uses task information during the module identification process.
      DsNM3F extends our previous space-by-time decomposition method (the so-called
      sNM3F algorithm, which could assess task performance only after having computed
      modules) to identify modules gauging between two complementary objectives:
      reconstruction of the original data and reliable discrimination of the performed
      tasks. We show that DsNM3F recovers the task dependence of module activations
      more accurately than sNM3F. We also apply it to electromyographic signals
      recorded during performance of a variety of arm pointing tasks and identify
      spatial and temporal modules of muscle activity that are highly consistent with
      previous studies. DsNM3F achieves perfect task categorization without significant
      loss in data approximation when task information is available and generalizes as
      well as sNM3F when applied to new data. These findings suggest that the space-by
      time decomposition of muscle activity finds robust task-discriminating modular
      representations of muscle activity and that the insertion of task discrimination
      objectives is useful for describing the task modulation of module recruitment. 

PMID- 26217214
TI  - Direct and indirect spino-cerebellar pathways: shared ideas but different
      functions in motor control.
AB  - The impressive precision of mammalian limb movements relies on internal feedback
      pathways that convey information about ongoing motor output to cerebellar
      circuits. The spino-cerebellar tracts (SCT) in the cervical, thoracic and lumbar
      spinal cord have long been considered canonical neural substrates for the
      conveyance of internal feedback signals. Here we consider the distinct features
      of an indirect spino-cerebellar route, via the brainstem lateral reticular
      nucleus (LRN), and the implications of this pre-cerebellar "detour" for the
      execution and evolution of limb motor control. Both direct and indirect spino
      cerebellar pathways signal spinal interneuronal activity to the cerebellum during
      movements, but evidence suggests that direct SCT neurons are mainly modulated by
      rhythmic activity, whereas the LRN also receives information from systems active
      during postural adjustment, reaching and grasping. Thus, while direct and
      indirect spino-cerebellar circuits can both be regarded as internal copy
      pathways, it seems likely that the direct system is principally dedicated to
      rhythmic motor acts like locomotion, while the indirect system also provides a
      means of pre-cerebellar integration relevant to the execution and coordination of
      dexterous limb movements. 

PMID- 26217215
TI  - Embodied learning of a generative neural model for biological motion perception
      and inference.
AB  - Although an action observation network and mirror neurons for understanding the
      actions and intentions of others have been under deep, interdisciplinary
      consideration over recent years, it remains largely unknown how the brain manages
      to map visually perceived biological motion of others onto its own motor system.
      This paper shows how such a mapping may be established, even if the biologically
      motion is visually perceived from a new vantage point. We introduce a learning
      artificial neural network model and evaluate it on full body motion tracking
      recordings. The model implements an embodied, predictive inference approach. It
      first learns to correlate and segment multimodal sensory streams of own bodily
      motion. In doing so, it becomes able to anticipate motion progression, to
      complete missing modal information, and to self-generate learned motion
      sequences. When biological motion of another person is observed, this self
      knowledge is utilized to recognize similar motion patterns and predict their
      progress. Due to the relative encodings, the model shows strong robustness in
      recognition despite observing rather large varieties of body morphology and
      posture dynamics. By additionally equipping the model with the capability to
      rotate its visual frame of reference, it is able to deduce the visual perspective
      onto the observed person, establishing full consistency to the embodied self
      motion encodings by means of active inference. In further support of its neuro
      cognitive plausibility, we also model typical bistable perceptions when crucial
      depth information is missing. In sum, the introduced neural model proposes a
      solution to the problem of how the human brain may establish correspondence
      between observed bodily motion and its own motor system, thus offering a
      mechanism that supports the development of mirror neurons. 

PMID- 26217216
TI  - Impacts of clustering on noise-induced spiking regularity in the excitatory
      neuronal networks of subnetworks.
AB  - In this paper, we investigate how clustering factors influent spiking regularity
      of the neuronal network of subnetworks. In order to do so, we fix the averaged
      coupling probability and the averaged coupling strength, and take the cluster
      number M, the ratio of intra-connection probability and inter-connection
      probability R, the ratio of intra-coupling strength and inter-coupling strength S
      as controlled parameters. With the obtained simulation results, we find that
      spiking regularity of the neuronal networks has little variations with changing
      of R and S when M is fixed. However, cluster number M could reduce the spiking
      regularity to low level when the uniform neuronal network's spiking regularity is
      at high level. Combined the obtained results, we can see that clustering factors
      have little influences on the spiking regularity when the entire energy is fixed,
      which could be controlled by the averaged coupling strength and the averaged
      connection probability. 

PMID- 26217217
TI  - Conduction block in myelinated axons induced by high-frequency (kHz) non
      symmetric biphasic stimulation.
AB  - This study used the Frankenhaeuser-Huxley axonal model to analyze the effects of
      non-symmetric waveforms on conduction block of myelinated axons induced by high
      frequency (10-300 kHz) biphasic electrical stimulation. The results predict a
      monotonic relationship between block threshold and stimulation frequency for
      symmetric waveform and a non-monotonic relationship for non-symmetric waveforms.
      The symmetric waveform causes conduction block by constantly activating both
      sodium and potassium channels at frequencies of 20-300 kHz, while the non
      symmetric waveforms share the same blocking mechanism from 20 kHz up to the peak
      threshold frequency. At the frequencies above the peak threshold frequency the
      non-symmetric waveforms block axonal conduction by either hyperpolarizing the
      membrane (if the positive pulse is longer) or depolarizing the membrane (if the
      negative pulse is longer). This simulation study further increases our
      understanding of conduction block in myelinated axons induced by high-frequency
      biphasic electrical stimulation, and can guide future animal experiments as well
      as optimize stimulation parameters that might be used for electrically induced
      nerve block in clinical applications. 

PMID- 26217218
TI  - Homeostatic role of heterosynaptic plasticity: models and experiments.
AB  - Homosynaptic Hebbian-type plasticity provides a cellular mechanism of learning
      and refinement of connectivity during development in a variety of biological
      systems. In this review we argue that a complimentary form of plasticity
      heterosynaptic plasticity-represents a necessary cellular component for
      homeostatic regulation of synaptic weights and neuronal activity. The required
      properties of a homeostatic mechanism which acutely constrains the runaway
      dynamics imposed by Hebbian associative plasticity have been well-articulated by
      theoretical and modeling studies. Such mechanism(s) should robustly support the
      stability of operation of neuronal networks and synaptic competition, include
      changes at non-active synapses, and operate on a similar time scale to Hebbian
      type plasticity. The experimentally observed properties of heterosynaptic
      plasticity have introduced it as a strong candidate to fulfill this homeostatic
      role. Subsequent modeling studies which incorporate heterosynaptic plasticity
      into model neurons with Hebbian synapses (utilizing an STDP learning rule) have
      confirmed its ability to robustly provide stability and competition. In contrast,
      properties of homeostatic synaptic scaling, which is triggered by extreme and
      long lasting (hours and days) changes of neuronal activity, do not fit two
      crucial requirements for a hypothetical homeostatic mechanism needed to provide
      stability of operation in the face of on-going synaptic changes driven by Hebbian
      type learning rules. Both the trigger and the time scale of homeostatic synaptic
      scaling are fundamentally different from those of the Hebbian-type plasticity. We
      conclude that heterosynaptic plasticity, which is triggered by the same episodes
      of strong postsynaptic activity and operates on the same time scale as Hebbian
      type associative plasticity, is ideally suited to serve a homeostatic role during
      on-going synaptic plasticity. 

PMID- 26217219
TI  - Potential of adipose-derived stem cells in muscular regenerative therapies.
AB  - Regenerative capacity of skeletal muscles resides in satellite cells, a self
      renewing population of muscle cells. Several studies are investigating epigenetic
      mechanisms that control myogenic proliferation and differentiation to find new
      approaches that could boost regeneration of endogenous myogenic progenitor
      populations. In recent years, a lot of effort has been applied to purify, expand
      and manipulate adult stem cells from muscle tissue. However, this population of
      endogenous myogenic progenitors in adults is limited and their access is
      difficult and invasive. Therefore, other sources of stem cells with potential to
      regenerate muscles need to be examined. An excellent candidate could be a
      population of adult stromal cells within fat characterized by mesenchymal
      properties, which have been termed adipose-derived stem cells (ASCs). These
      progenitor adult stem cells have been successfully differentiated in vitro to
      osteogenic, chondrogenic, neurogenic and myogenic lineages. Autologous ASCs are
      multipotent and can be harvested with low morbidity; thus, they hold promise for
      a range of therapeutic applications. This review will summarize the use of ASCs
      in muscle regenerative approaches. 

PMID- 26217221
TI  - An Interactive Web Tool for Facilitating Shared Decision-Making in Dementia-Care
      Networks: A Field Study.
AB  - BACKGROUND: An interactive web tool has been developed for facilitating shared
      decision-making in dementia-care networks. The DecideGuide provides a chat
      function for easier communication between network members, a deciding together
      function for step-by-step decision-making, and an individual opinion function for
      eight dementia-related life domains. The aim of this study was to gain insight in
      the user friendliness of the DecideGuide, user acceptance and satisfaction, and
      participants' opinion of the DecideGuide for making decisions. MATERIALS AND
      METHODS: A 5-month field study included four dementia-care networks (19
      participants in total). The data derived from structured interviews,
      observations, and information that participants logged in the DecideGuide.
      Structured interviews took place at the start, middle, and end of the field study
      with people with dementia, informal caregivers, and case managers. Four
      observations of case managers' home visits focused on members' responses and use
      of the tool. RESULTS: (1) The user friendliness of the chat and individual
      opinion functions was adequate for case managers and most informal caregivers.
      Older participants, with or without dementia, had some difficulties using a
      tablet and the DecideGuide. The deciding together function does not yet provide
      adequate instructions for all. The user interface needs simplification. (2) User
      acceptance and satisfaction: everybody liked the chat's easy communication,
      handling difficult issues for discussion, and the option of individual opinions.
      (3) The DecideGuide helped participants structure their thoughts. They felt more
      involved and shared more information about daily issues than they had done
      previously. CONCLUSION: Participants found the DecideGuide valuable in decision
      making. The chat function seems powerful in helping members engage with one
      another constructively. Such engagement is a prerequisite for making shared
      decisions. Regardless of participants' use of the tool, they saw the
      DecideGuide's added value.

PMID- 26217220
TI  - Muscle wasting in myotonic dystrophies: a model of premature aging.
AB  - Myotonic dystrophy type 1 (DM1 or Steinert's disease) and type 2 (DM2) are
      multisystem disorders of genetic origin. Progressive muscular weakness, atrophy
      and myotonia are the most prominent neuromuscular features of these diseases,
      while other clinical manifestations such as cardiomyopathy, insulin resistance
      and cataracts are also common. From a clinical perspective, most DM symptoms are
      interpreted as a result of an accelerated aging (cataracts, muscular weakness and
      atrophy, cognitive decline, metabolic dysfunction, etc.), including an increased
      risk of developing tumors. From this point of view, DM1 could be described as a
      progeroid syndrome since a notable age-dependent dysfunction of all systems
      occurs. The underlying molecular disorder in DM1 consists of the existence of a
      pathological (CTG) triplet expansion in the 3' untranslated region (UTR) of the
      Dystrophia Myotonica Protein Kinase (DMPK) gene, whereas (CCTG)n repeats in the
      first intron of the Cellular Nucleic acid Binding Protein/Zinc Finger Protein 9
      (CNBP/ZNF9) gene cause DM2. The expansions are transcribed into (CUG)n and
      (CCUG)n-containing RNA, respectively, which form secondary structures and
      sequester RNA-binding proteins, such as the splicing factor muscleblind-like
      protein (MBNL), forming nuclear aggregates known as foci. Other splicing factors,
      such as CUGBP, are also disrupted, leading to a spliceopathy of a large number of
      downstream genes linked to the clinical features of these diseases. Skeletal
      muscle regeneration relies on muscle progenitor cells, known as satellite cells,
      which are activated after muscle damage, and which proliferate and differentiate
      to muscle cells, thus regenerating the damaged tissue. Satellite cell dysfunction
      seems to be a common feature of both age-dependent muscle degeneration
      (sarcopenia) and muscle wasting in DM and other muscle degenerative diseases.
      This review aims to describe the cellular, molecular and macrostructural
      processes involved in the muscular degeneration seen in DM patients, highlighting
      the similarities found with muscle aging. 

PMID- 26217223
TI  - Gray matter blood flow and volume are reduced in association with white matter
      hyperintensity lesion burden: a cross-sectional MRI study.
AB  - Cerebral White Matter Hyperintensities (WMH) are associated with vascular risk
      factors and age-related cognitive decline. WMH have primarily been associated
      with global white matter and gray matter (GM) changes and less is known about
      regional effects in GM. The purpose of this study was to test for an association
      between WMH and two GM imaging measures: cerebral blood flow (CBF) and voxel
      based morphometry (VBM). Twenty-six elderly adults with mild to severe WMH
      participated in this cross-sectional 3 Tesla magnetic resonance imaging (MRI)
      study. MRI measures of GM CBF and VBM were derived from arterial spin labeling
      (ASL) and T1-weighted images, respectively. Fluid-attenuated inversion recovery
      (FLAIR) images were used to quantify the WMH lesion burden (mL). GM CBF and VBM
      data were used as dependent variables. WMH lesion burden, age and sex were used
      in a regression model. Visual rating of WMH with the Fazekas method was used to
      compare the WMH lesion volume regression approach. WMH volume was normally
      distributed for this group (mean volume of 22.7 mL, range: 2.2-70.6 mL). CBF
      analysis revealed negative associations between WMH volume and CBF in the left
      anterior putamen, subcallosal, accumbens, anterior caudate, orbital frontal,
      anterior insula, and frontal pole (corrected p < 0.05). VBM analysis revealed
      negative associations between WMH and GM volume in lingual gyrus, intracalcarine,
      and bilateral hippocampus (corrected p < 0.05). The visual rating scale
      corroborated the regression findings (corrected p < 0.05). WMH lesion volume was
      associated with intra-group GM CBF and structural differences in this cohort of
      WMH adults with mild to severe lesion burden. 

PMID- 26217222
TI  - Menopause, obesity and inflammation: interactive risk factors for Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder, the
      development of which is regulated by several environmental and genetic risk
      factors. Two factors theorized to contribute to the initiation and/or progression
      of AD pathogenesis are age-related increases in inflammation and obesity. These
      factors may be particularly problematic in women. The onset of menopause in mid
      life elevates the vulnerability of women to AD, an increased risk that is likely
      associated with the depletion of estrogens. Menopause is also linked with an
      abundance of additional changes, including increased central adiposity and
      inflammation. Here, we review the current literature to explore the interactions
      between obesity, inflammation, menopause and AD. 

PMID- 26217224
TI  - Components of a Mediterranean diet and their impact on cognitive functions in
      aging.
AB  - BACKGROUND: Adhering to the Mediterranean diet (MeDi) is known to be beneficial
      with regard to many age-associated diseases including cardiovascular diseases and
      type 2 diabetes. Recent studies also suggest an impact on cognition and brain
      structure, and increasing effort is made to track effects down to single
      nutrients. AIMS: We aimed to review whether two MeDi components, i.e., long-chain
      omega-3 fatty acids (LC-n3-FA) derived from sea-fish, and plant polyphenols
      including resveratrol (RSV), exert positive effects on brain health in aging.
      CONTENT: We summarized health benefits associated with the MeDi and evaluated
      available studies on the effect of (1) fish-consumption and LC-n3-FA
      supplementation as well as (2) diet-derived or supplementary polyphenols such as
      RSV, on cognitive performance and brain structure in animal models and human
      studies. Also, we discussed possible underlying mechanisms. CONCLUSION: A
      majority of available studies suggest that consumption of LC-n3-FA with fish or
      fishoil-supplements exerts positive effects on brain health and cognition in
      older humans. However, more large-scale randomized controlled trials are needed
      to draw definite recommendations. Considering polyphenols and RSV, only few
      controlled studies are available to date, yet the evidence based on animal
      research and first interventional human trials is promising and warrants further
      investigation. In addition, the concept of food synergy within the MeDi
      encourages future trials that evaluate the impact of comprehensive lifestyle
      patterns to help maintaining cognitive functions into old age.

PMID- 26217225
TI  - Evaluation of sodium nitroprusside for controlled hypotension in children during
      surgery.
AB  - PURPOSE: (1) To define the onset and offset of the blood-pressure-lowering
      effects of sodium nitroprusside (SNP) for use in developing instructions for dose
      titration in children undergoing a surgical or medical procedure, and (2) to
      assess the safety of SNP administration in pediatric patients requiring
      controlled reduction of blood pressure. METHODS: We conducted a randomized,
      double-blind, parallel-group, dose-ranging, effect-controlled, multicenter study
      of intravenous (IV) infusions of SNP in pediatric patients <17 years, who
      required controlled hypotension for at least 2 h while undergoing a surgical or
      medical procedure. A blinded SNP dose of 0.3, 1, 2, or 3 MUg/kg/min was infused
      for 30 min, followed by open-label administration for at least 90 min. Both
      infusions were titrated to effect. RESULTS: The final intent-to-treat group
      comprised 203 patients. Significant reductions in mean arterial pressure (MAP)
      from baseline were observed for all four doses at 20 and 25 min after the start
      of infusion (p <= 0.009 and p <= 0.010 for each time, respectively). Overall,
      98.5% of the patients achieved the target MAP; 72.9% first achieved the target
      MAP during the blinded infusion. The mean infusion rate at target MAP was 1.07
      MUg/kg/min. CONCLUSION: We determined that 0.3 MUg/kg/m is a reasonable starting
      dose for SNP in pediatric patients requiring controlled hypotension. The infusion
      rate can then be increased to achieve the desired reduction in blood pressure. On
      the basis of our results, we found an average infusion rate of 1 MUg/kg/min might
      be appropriate. Of note, no cyanide toxicity was reported, and no measureable
      cyanide levels were detected in any blood samples obtained during the study.
      http://clinicaltrials.gov/show/NCT00135668.

PMID- 26217227
TI  - Evaluation of nano spray drying as a method for drying and formulation of
      therapeutic peptides and proteins.

PMID- 26217228
TI  - Editorial: Phosphoinositides and their phosphatases: Linking electrical and
      chemical signals in biological processes.

PMID- 26217226
TI  - Sonochemotherapy: from bench to bedside.
AB  - The combination of microbubbles and ultrasound has emerged as a promising method
      for local drug delivery. Microbubbles can be locally activated by a targeted
      ultrasound beam, which can result in several bio-effects. For drug delivery,
      microbubble-assisted ultrasound is used to increase vascular- and plasma membrane
      permeability for facilitating drug extravasation and the cellular uptake of drugs
      in the treated region, respectively. In the case of drug-loaded microbubbles,
      these two mechanisms can be combined with local release of the drug following
      destruction of the microbubble. The use of microbubble-assisted ultrasound to
      deliver chemotherapeutic agents is also referred to as sonochemotherapy. In this
      review, the basic principles of sonochemotherapy are discussed, including aspects
      such as the type of (drug-loaded) microbubbles used, the routes of administration
      used in vivo, ultrasound devices and parameters, treatment schedules and safety
      issues. Finally, the clinical translation of sonochemotherapy is discussed,
      including the first clinical study using sonochemotherapy. 

PMID- 26217229
TI  - Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine
      hydrochloride.
AB  - The aim of the present research was to develop a bilayer tablet of venlafaxine
      hydrochloride for bimodal drug release. In the present investigation authors have
      tried to explore fenugreek mucilage (FNM) for bioadhesive sustained release
      layer. The attempt has been made to combine FNM with well studied bioadhesive
      polymers like hydroxy propyl methyl cellulose (HPMC), Carbopol, and Xanthan Gum.
      The formulations were evaluated for swelling Index, ex vivo bioadhesion, water
      uptake studies, in vitro drug release and dissolution kinetics was studied.
      Substantial bioadhesion force (2.4 +/- 0.023 g) and tablet adhesion retention
      time (24 +/- 2 h) was observed with FNM and HPMC combination at 80:20 ratio. The
      dissolution kinetics followed the Higuchi model (R (2) = 0.9913) via a non
      Fickian diffusion controlled release mechanism after the initial burst. The 3(2)
      full factorial design was employed in the present study. The type of polymers
      used in combination with FNM (X1) and percent polymer replaced with FNM (X2) were
      taken as independent formulations variables. The selected responses, bioadhesion
      force (0.11-0.25 +/- 0.023 g), amount of drug released in 10 h, Y10 (78.20-95.78
      +/- 1.24%) and bioadhesive strength, (19-24 +/- 2 h) presented good correlation
      with the selected independent variables. Statistical analysis (ANOVA) of the
      optimized bilayer formulations showed no significant difference in the cumulative
      amount of drug release after 15 min, but significant difference (p < 0.05) in the
      amount of drug released after 1 hr till 12 h from optimized formulations was
      observed. The natural mucilage like FNM could be successfully incorporated into
      tablet with only 20% replacement with HPMC and it showed good bioadhesiveness and
      sustained drug release. 

PMID- 26217230
TI  - A novel, dynamic pattern-based analysis of NF-kappaB binding during the priming
      phase of liver regeneration reveals switch-like functional regulation of target
      genes.
AB  - Following partial hepatectomy, a coordinated series of molecular events occurs to
      regulate hepatocyte entry into the cell cycle to recover lost mass. In rats
      during the first 6 h following resection, hepatocytes are primed by a tightly
      controlled cytokine response to prepare hepatocytes to begin replication.
      Although it appears to be a critical element driving regeneration, the cytokine
      response to resection has not yet been fully characterized. Specifically, the
      role of one of the key response elements to cytokine signaling (NF-kappaB)
      remains incompletely characterized. In this study, we present a novel, genome
      wide, pattern-based analysis characterizing NF-kappaB binding during the priming
      phase of liver regeneration. We interrogated the dynamic regulation of priming by
      NF-kappaB through categorizing NF-kappaB binding in different temporal profiles:
      immediate sustained response, early transient response, and delayed response to
      partial hepatectomy. We then identified functional regulation of NF-kappaB
      binding by relating the temporal response profile to differential gene
      expression. We found that NF-kappaB bound genes govern negative regulation of
      cell growth and inflammatory response immediately following hepatectomy. NF
      kappaB also transiently regulates genes responsible for lipid biosynthesis and
      transport as well as induction of apoptosis following hepatectomy. By the end of
      the priming phase, NF-kappaB regulation of genes involved in inflammatory
      response, negative regulation of cell death, and extracellular structure
      organization became prominent. These results suggest that NF-kappaB regulates
      target genes through binding and unbinding in immediate, transient, and delayed
      patterns. Such dynamic switch-like patterns of NF-kappaB binding may govern
      different functional transitions that drive the onset of regeneration. 

PMID- 26217231
TI  - Zinc and copper levels are not correlated with angiographically-defined coronary
      artery disease in sudanese patients.
AB  - We investigated zinc and copper levels in angiographically defined obstructive
      coronary artery disease (CAD) in patients undergoing elective coronary
      angiography in El-Shaab Hospital, Sudan. We performed a cross-sectional study.
      One hundred forty-two patients were enrolled. Sociodemographic and medical
      characteristics were collected using a questionnaire. Glucose, lipid, zinc, and
      copper levels were measured. Out of 142 patients, 102 (71.8%) had CAD and 40
      (28.2%) had patent coronary arteries. There were no significant differences in
      median (interquartile range) zinc [118.5 (97.2-151.0) vs. 130.0 (106.0-174.0)
      MUg/ml, P = 0.120] and copper [150.6 (125.0-183.0) vs. 158 (132.0-180.0) MUg/mL,
      P = 0.478] levels between patients with CAD and those with patent coronary
      arteries. In linear regression analysis, there were no associations between CAD
      and zinc and copper levels. The current study failed to show any significant
      association between CAD and zinc and copper levels. 

PMID- 26217232
TI  - Device-based approaches for renal nerve ablation for hypertension and beyond.
AB  - Animal and human studies have demonstrated that chronic activation of renal
      sympathetic nerves is critical in the pathogenesis and perpetuation of treatment
      resistant hypertension. Bilateral renal denervation has emerged as a safe and
      effective, non-pharmacological treatment for resistant hypertension that involves
      the selective ablation of efferent and afferent renal nerves to lower blood
      pressure. However, the most recent and largest randomized controlled trial failed
      to confirm the primacy of renal denervation over a sham procedure, prompting
      widespread re-evaluation of the therapy's efficacy. Disrupting renal afferent
      sympathetic signaling to the hypothalamus with renal denervation lowers central
      sympathetic tone, which has the potential to confer additional clinical benefits
      beyond blood pressure control. Specifically, there has been substantial interest
      in the use of renal denervation as either a primary or adjunct therapy in
      pathological conditions characterized by central sympathetic overactivity such as
      renal disease, heart failure and metabolic-associated disorders. Recent findings
      from pre-clinical and proof-of-concept studies appear promising with renal
      denervation shown to confer cardiovascular and metabolic benefits, largely
      independent of changes in blood pressure. This review explores the pathological
      rationale for targeting sympathetic renal nerves for blood pressure control.
      Latest developments in renal nerve ablation modalities designed to improve
      procedural success are discussed along with prospective findings on the efficacy
      of renal denervation to lower blood pressure in treatment-resistant hypertensive
      patients. Preliminary evidence in support of renal denervation as a possible
      therapeutic option in disease states characterized by central sympathetic
      overactivity is also presented. 

PMID- 26217233
TI  - NOX signaling in molecular cardiovascular mechanisms involved in the blood
      pressure homeostasis.
AB  - Blood pressure homeostasis is maintained by several mechanisms regulating cardiac
      output, vascular resistances, and blood volume. At cellular levels, reactive
      oxygen species (ROS) signaling is involved in multiple molecular mechanisms
      controlling blood pressure. Among ROS producing systems, NADPH oxidases (NOXs),
      expressed in different cells of the cardiovascular system, are the most important
      enzymes clearly linked to the development of hypertension. NOXs exert a central
      role in cardiac mechanosensing, endothelium-dependent relaxation, and Angiotensin
      II (Ang-II) redox signaling regulating vascular tone. The central role of NOXs in
      redox-dependent cardiovascular cell functions renders these enzymes a promising
      pharmacological target for the treatment of cardiovascular diseases, including
      hypertension. The aim of the present review is to focus on the physiological role
      of the cardiovascular NOX-generating ROS in the molecular and cellular mechanisms
      affecting blood pressure. 

PMID- 26217235
TI  - Editorial: Cardiac electronic remodeling and susceptibility to arrhythmias: an
      introduction and brief historical overview.

PMID- 26217234
TI  - Uninephrectomy in rats on a fixed food intake results in adipose tissue lipolysis
      implicating spleen cytokines.
AB  - The role of mild kidney dysfunction in altering lipid metabolism and promoting
      inflammation was investigated in uninephrectomized rats (UniNX) compared to Sham
      operated controls rats. The impact of UniNX was studied 1, 2, and 4 weeks after
      UniNX under mild food restriction at 90% of ad libitum intake to ensure the same
      caloric intake in both groups. UniNX resulted in the reduction of fat pad weight.
      UniNX was associated with increased circulating levels of beta-hydroxybutyrate
      and glycerol, as well as increased fat pad mRNA of hormone sensitive lipase and
      adipose triglyceride lipase, suggesting enhanced lipolysis. No decrease in fat
      pad lipogenesis as assessed by fatty acid synthase activity was observed.
      Circulating hormones known to regulate lipolysis such as leptin, T3, ghrelin,
      insulin, corticosterone, angiotensin 1, and angiotensin 2 were not different
      between the two groups. In contrast, a select group of circulating lipolytic
      cytokines, including interferon-gamma and granulocyte macrophage-colony
      stimulating factor, were increased after UniNX. These cytokine levels were
      elevated in the spleen, but decreased in the kidney, liver, and fat pads. This
      could be explained by anti-inflammatory factors SIRT1, a member of the sirtuins,
      and the farnesoid x receptor (FXR), which were decreased in the spleen but
      elevated in the kidney, liver, and fat pads (inguinal and epididymal). Our study
      suggests that UniNX induces adipose tissue lipolysis in response to increased
      levels of a subset of lipolytic cytokines of splenic origin. 

PMID- 26217236
TI  - Nonlinear parameters of surface EMG in schizophrenia patients depend on kind of
      antipsychotic therapy.
AB  - We compared a set of surface EMG (sEMG) parameters in several groups of
      schizophrenia (SZ, n = 74) patients and healthy controls (n = 11) and coupled
      them with the clinical data. sEMG records were quantified with spectral, mutual
      information (MI) based and recurrence quantification analysis (RQA) parameters,
      and with approximate and sample entropies (ApEn and SampEn). Psychotic
      deterioration was estimated with Positive and Negative Syndrome Scale (PANSS) and
      with the positive subscale of PANSS. Neuroleptic-induced parkinsonism (NIP) motor
      symptoms were estimated with Simpson-Angus Scale (SAS). Dyskinesia was measured
      with Abnormal Involuntary Movement Scale (AIMS). We found that there was no
      difference in values of sEMG parameters between healthy controls and drug-naive
      SZ patients. The most specific group was formed of SZ patients who were
      administered both typical and atypical antipsychotics (AP). Their sEMG parameters
      were significantly different from those of SZ patients taking either typical or
      atypical AP or taking no AP. This may represent a kind of synergistic effect of
      these two classes of AP. For the clinical data we found that PANSS, SAS, and AIMS
      were not correlated to any of the sEMG parameters. CONCLUSION: with nonlinear
      parameters of sEMG it is possible to reveal NIP in SZ patients, and it may help
      to discriminate between different clinical groups of SZ patients. Combined
      typical and atypical AP therapy has stronger effect on sEMG than a therapy with
      AP of only one class.

PMID- 26217237
TI  - Serum PINP, PIIINP, galectin-3, and ST2 as surrogates of myocardial fibrosis and
      echocardiographic left venticular diastolic filling properties.
AB  - OBJECTIVES AND BACKGROUND: Serum biomarkers have been proposed to reflect
      fibrosis of several human tissues, but their specific role in the detection of
      myocardial fibrosis has not been well-established. We studied the association
      between N-terminal propeptide of type I and III procollagen (PINP, PIIINP,
      respectively), galectin-3 (gal-3), soluble ST2 (ST2), and myocardial fibrosis
      measured by late gadolinium enhanced cardiac magnetic resonance imaging (LGE CMR)
      and their relation to left ventricular diastolic filling properties measured by
      tissue Doppler echocardiography (E/e') in patients with stable coronary artery
      disease (CAD). METHODS AND RESULTS: We determined the PINP, PIIINP, gal-3, and
      ST2 serum levels and performed LGE CMR and echocardiography on 63 patients with
      stable CAD without a history of prior myocardial infarction. Myocardial late
      gadolinium enhancement T1 relaxation time was defined as a specific marker of
      myocardial fibrosis. ST2, PINP, and PIIINP did not have a significant correlation
      with the post-LGE T1 relaxation time tertiles (NS for all), but the lowest post
      LGE T1 relaxation time tertile had significantly higher gal-3 values than the
      other two tertiles (p = 0.002 and 0.002) and higher E/e-values (p = 0.009)
      compared to the highest T1 relaxation time tertile. ST2 (p = 0.025 and 0.029),
      gal-3 (p = 0.003 and < 0.001) and PIIINP (p = 0.001 and 0.007) levels were also
      significantly higher in the highest E/e tertile, compared to the other two
      tertiles. CONCLUSIONS: Elevated serum levels of gal-3 reflect the degree of
      myocardial fibrosis assessed by LGE CMR. Gal-3, ST2, and PIIINP are also elevated
      in patients with impaired LV diastolic function, suggesting that these biomarkers
      are useful surrogates of structural and functional abnormality of the myocardium.

PMID- 26217238
TI  - Characteristics of Social Network Gamers: Results of an Online Survey.
AB  - Current research on Internet addiction (IA) reported moderate to high prevalence
      rates of IA and comorbid psychiatric symptoms in users of social networking sites
      (SNS) and online role-playing games. The aim of this study was to characterize
      adult users of an Internet multiplayer strategy game within a SNS. Therefore, we
      conducted an exploratory study using an online survey to assess sociodemographic
      variables, psychopathology, and the rate of IA in a sample of adult social
      network gamers by Young's Internet Addiction Test (IAT), the Toronto Alexithymia
      Scale (TAS-26), the Beck Depression Inventory-II (BDI-II), the Symptom Checklist
      90-R (SCL-90-R), and the WHO Quality of Life-BREF (WHOQOL-BREF). All participants
      were listed gamers of "Combat Zone" in the SNS "Facebook." In this sample, 16.2%
      of the participants were categorized as subjects with IA and 19.5% fulfilled the
      criteria for alexithymia. Comparing study participants with and without IA, the
      IA group had significantly more subjects with alexithymia, reported more
      depressive symptoms, and showed poorer quality of life. These findings suggest
      that social network gaming might also be associated with maladaptive patterns of
      Internet use. Furthermore, a relationship between IA, alexithymia, and depressive
      symptoms was found that needs to be elucidated by future studies. 

PMID- 26217239
TI  - Sex Differences in the Reinstatement of Methamphetamine Seeking after Forced
      Abstinence in Sprague-Dawley Rats.
AB  - Preventing relapse to drug abuse is one of the struggles faced by clinicians in
      order to treat patients with substance use disorders (DSM-5). There is a large
      body of clinical evidence suggesting differential characteristics of the disorder
      in men and women, which is in line with preclinical findings as well. The aim of
      this study was to assess differences in relapse-like behavior in methamphetamine
      (METH) seeking after a period of forced abstinence, which simulates the real
      clinical situation very well. Findings from such study might add new insights in
      gender differences in relapse mechanisms to previous studies, which employ a
      classical drug or cue-induced reinstatement procedure following the extinction
      training. Adult male and female Sprague-Dawley rats were used in IV self
      administration procedure conducted in operant boxes using nose-poke operandi
      (Coulborn Instruments, USA). Active nose-poke resulted in activation of the
      infusion pump to deliver one intravenous infusion of METH (0.08 mg/kg). After
      baseline drug intake was established (maintenance phase), a period of forced
      abstinence was initiated and rats were kept singly in their home cages for 14
      days. Finally, one reinstatement session in operant boxes was conducted. Females
      were found to self-administer significantly lower dose of METH. The relapse rate
      was assessed as a number of active nose-pokes during the reinstatement session,
      expressed as a percentage of active nose-poking during the maintenance phase.
      Females displayed approximately 300% of active nose-pokes compared to 50% in
      males. This indicates higher vulnerability to relapse of METH seeking behavior in
      female rats. This effect was detected in all females, independently of current
      phase of their estrous cycle. Therefore, this paradigm using operant drug self
      administration and reinstatement of drug-seeking after forced abstinence model
      can be used for preclinical screening for potential new anti-relapse medications
      specific for women. 

PMID- 26217240
TI  - The Role of Mental Imagery in Depression: Negative Mental Imagery Induces Strong
      Implicit and Explicit Affect in Depression.
AB  - Mental imagery, seeing with the mind's eyes, can induce stronger positive as well
      as negative affect compared to verbal processing. Given this emotion-amplifying
      effect, it appears likely that mental images play an important role in affective
      disorders. According to the subcomponents model of depression, depressed mood is
      maintained by both negative imagery (which amplifies negative mood) and less
      efficient positive imagery processes. Empirical research on the link between
      mental imagery and affect in clinical depression, however, is still sparse. This
      study aimed at testing the role of mental imagery in depression, using a modified
      version of the affect misattribution procedure (AMP) and the self-assessment
      manikin (SAM) to assess implicit (AMP) and explicit (SAM) affect elicited by
      mental images, pictures, and verbal processing in clinically depressed
      participants (n = 32) compared to healthy controls (n = 32). In individuals with
      a depressive disorder, compared to healthy controls, negative mental images
      induced stronger negative affect in the explicit as well as implicit measure.
      Negative mental imagery did not, however, elicit greater increases in explicitly
      and implicitly assessed negative affect compared to other processing modalities
      (verbal processing, pictures) in the depressed group. Additionally, a positive
      imagery deficit in depression was observed in the explicit measure.
      Interestingly, the two groups did not differ in implicitly assessed affect after
      positive imagery, indicating that depressed individuals might benefit from
      positive imagery on an implicit or automatic level. Overall, our findings suggest
      that mental imagery also plays an important role in depression and confirm the
      potential of novel treatment approaches for depression, such as the promotion of
      positive imagery. 

PMID- 26217241
TI  - A Bayesian Approach to Latent Class Modeling for Estimating the Prevalence of
      Schizophrenia Using Administrative Databases.
AB  - Estimating the incidence and the prevalence of psychotic disorders in the
      province of Quebec has been the object of some interest in recent years as a
      contribution to the epidemiological study of the causes of psychotic disorders
      being carried out primarily in UK and Scandinavia. A number of studies have used
      administrative data from the Regie de l'assurance maladie du Quebec (RAMQ) that
      includes nearly all Quebec citizens to obtain geographical and temporal
      prevalence estimates for the illness. However, there has been no investigation of
      the validity of RAMQ diagnoses for psychotic disorders, and without a measure of
      the sensitivity and the specificity of these diagnoses, it is impossible to be
      confident in the accuracy of the estimates obtained. This paper proposes the use
      of latent class analysis to ascertain the validity of a diagnosis of
      schizophrenia using RAMQ data. 

PMID- 26217242
TI  - Neurobiology of Maternal Stress: Role of Social Rank and Central Oxytocin in
      Hypothalamic-Pituitary Adrenal Axis Modulation.
AB  - BACKGROUND: Chronic stress may conceivably require plasticity of maternal
      physiology and behavior to cope with the conflicting primary demands of infant
      rearing and foraging for food. In addition, social rank may play a pivotal role
      in mandating divergent homeostatic adaptations in cohesive social groups. We
      examined cerebrospinal fluid (CSF) oxytocin (OT) levels and hypothalamic
      pituitary adrenal (HPA) axis regulation in the context of maternal social stress
      and assessed the contribution of social rank to dyadic distance as reflective of
      distraction from normative maternal-infant interaction. METHODS: Twelve socially
      housed mother-infant bonnet macaque dyads were studied after variable foraging
      demand (VFD) exposure compared to 11 unstressed dyads. Dyadic distance was
      determined by behavioral observation. Social ranking was performed blindly by two
      observers. Post-VFD maternal plasma cortisol and CSF OT were compared to
      corresponding measures in non-VFD-exposed mothers. RESULTS: High-social rank was
      associated with increased dyadic distance only in VFD-exposed dyads and not in
      control dyads. In mothers unexposed to VFD, social rank was not related to
      maternal cortisol levels, whereas VFD-exposed dominant versus subordinate mothers
      exhibited increased plasma cortisol. Maternal CSF OT directly predicted maternal
      cortisol only in VFD-exposed mothers. CSF OT was higher in dominant versus
      subordinate mothers. VFD-exposed mothers with "high" cortisol specifically
      exhibited CSF OT elevations in comparison to control groups. CONCLUSION: Pairing
      of maternal social rank to dyadic distance in VFD presumably reduces maternal
      contingent responsivity, with ensuing long-term sequelae. VFD-exposure
      dichotomizes maternal HPA-axis response as a function of social rank with
      relatively reduced cortisol in subordinates. OT may serve as a homeostatic buffer
      during maternal stress exposure.

PMID- 26217243
TI  - Psychiatric Stigma in Treatment-Seeking Adults with Personality Problems:
      Evidence from a Sample of 214 Patients.
AB  - Stigmatization is a major burden in adult psychiatric patients with Axis-I
      diagnoses, as shown consistently in most studies. Significantly fewer studies on
      the emergence of psychiatric stigma in adult patients with personality disorders
      (PDs) exist, although the resulting evidence is conclusive. Some authors consider
      patients with PDs at risk for severe stigmatization because of intense
      difficulties during interpersonal contact, even in a psychotherapeutic
      relationship. The aim of this study was primarily the assessment of pre-existing
      stigma in patients referred for intensive treatment for PDs. The study enrolled
      214 patients admitted to the adult department of a highly specialized mental
      health care institute offering psychotherapy for patients with severe and complex
      personality pathology. All patients underwent a standard assessment with self
      report questionnaires and a semi-structured interview to measure Axis II PDs. The
      stigma consciousness questionnaire and the perceived devaluation-discrimination
      questionnaire, both validated instruments, were used to measure perceived and
      actual experiences of stigma. Independent sample t-tests were used to investigate
      differences in the mean total stigma scores for patients both with and without a
      PD. One-way ANOVAs were performed to assess the differences between having a
      borderline PD, another PD, or no PD diagnosis. Multiple regression main effect
      analyses were conducted in order to explore the impact of the different PD
      diagnosis on the level of stigma. The mean scores across all patient groups were
      consistent with rather low stigma. No differences were found for patients with or
      without a PD diagnosis. Level of stigma in general was not associated with an
      accumulating number of PDs. Given the remarkable results, we would strongly
      recommend further investigations in the field to better understand the phenomenon
      of stigma in all its aspects. 

PMID- 26217244
TI  - The effects of subjective loss of control on risk-taking behavior: the mediating
      role of anger.
AB  - Based on the Appraisal Tendency Framework on the antecedents and consequences of
      emotions two experimental studies examined the relationship between externally
      caused loss of control experiences and risk-taking behavior, as well as the
      assumed mediation of this relationship by the emotion anger. An experimental
      paradigm for inducing externally caused and consequently externally attributed
      loss of control which should lead to experiences of anger was developed and
      pretested in a Pilot Study. The relationship between loss of control experiences,
      anger, and risk-taking behavior was investigated using two separate student
      samples from Germany (N = 84, 54% female) and China (N = 125; 64% female). In
      line with our hypotheses, results showed that anger mediated the link between
      subjective loss of control experiences and increasing risk-taking behavior.
      Multiple group comparisons revealing similar patterns in both samples affirmed
      the results' cross-cultural generalizability. These results implicate that anger
      makes people less risk averse in the process of economic decision making. 

PMID- 26217245
TI  - Non-verbal sensorimotor timing deficits in children and adolescents who stutter.
AB  - There is growing evidence that motor and speech disorders co-occur during
      development. In the present study, we investigated whether stuttering, a
      developmental speech disorder, is associated with a predictive timing deficit in
      childhood and adolescence. By testing sensorimotor synchronization abilities, we
      aimed to assess whether predictive timing is dysfunctional in young participants
      who stutter (8-16 years). Twenty German children and adolescents who stutter and
      43 non-stuttering participants matched for age and musical training were tested
      on their ability to synchronize their finger taps with periodic tone sequences
      and with a musical beat. Forty percent of children and 90% of adolescents who
      stutter displayed poor synchronization with both metronome and musical stimuli,
      falling below 2.5% of the estimated population based on the performance of the
      group without the disorder. Synchronization deficits were characterized by either
      lower synchronization accuracy or lower consistency or both. Lower accuracy
      resulted in an over-anticipation of the pacing event in participants who stutter.
      Moreover, individual profiles revealed that lower consistency was typical of
      participants that were severely stuttering. These findings support the idea that
      malfunctioning predictive timing during auditory-motor coupling plays a role in
      stuttering in children and adolescents. 

PMID- 26217246
TI  - Novel paradigms to measure variability of behavior in early childhood: posture,
      gaze, and pupil dilation.
AB  - A central challenge of investigating the underlying mechanisms of and the
      individual differences in young children's behavior is the measurement of the
      internal physiological mechanism and the involved expressive emotions. Here, we
      illustrate two paradigms that assess concurrent indicators of both children's
      social perception as well as their emotional expression. In one set of studies,
      children view situations while their eye movements are mapped onto a live scene.
      In these studies, children's internal arousal is measured via changes in their
      pupil dilation by using eye tracking technology. In another set of studies, we
      measured children's emotional expression via changes in their upper-body posture
      by using depth sensor imaging technology. Together, these paradigms can provide
      new insights into the internal mechanism and outward emotional expression
      involved in young children's behavior. 

PMID- 26217247
TI  - Economic games and social neuroscience methods can help elucidate the psychology
      of parochial altruism.

PMID- 26217248
TI  - The influence of information status on pronoun resolution in Mandarin Chinese:
      evidence from ERPs.
AB  - The purpose of this study is to shed light on the neural mechanisms underlying
      the modulation of pronoun resolution processes by the information status of the
      antecedent. Information status was manipulated by using a structurally based
      constraint (e.g., order of mention) as well as a pragmatically based constraint
      (i.e., topichood). We found that the pronouns referring to topic entities [the
      initial noun phrase (NP) in Subject-Object-Verb (SOV) structure in Experiment 1
      and OSV structure in Experiment 2] elicited attenuated P600 responses compared to
      the pronouns referring to non-topic entities (the initial NP in SVO structure or
      the second NP in OSV structure in both experiments) when potential interference
      from structural constraints was controlled. The linear structural constraint,
      namely the order of mention, had no clear influence on the P600 effect when the
      syntactic structural constraint was held constant (i.e., when both entities were
      syntactic subjects), regardless of whether one (Experiment 1) or two (Experiment
      2) animate antecedents were present. These findings suggest that pragmatically
      encoded features such as topichood and givenness can be processed separately from
      structural constraints such as order of mention to promote the salient status of
      a referent and thereby facilitate pronoun interpretation. 

PMID- 26217251
TI  - Narcissism predicts impulsive buying: phenotypic and genetic evidence.
AB  - Impulsive buying makes billions of dollars for retail businesses every year,
      particularly in an era of thriving e-commerce. Narcissism, characterized by
      impulsivity and materialism, may serve as a potential antecedent to impulsive
      buying. To test this hypothesis, two studies examined the relationship between
      narcissism and impulsive buying. In Study 1, we surveyed an online sample and
      found that while adaptive narcissism was not correlated with impulsive buying,
      maladaptive narcissism was significantly predictive of the impulsive buying
      tendency. By investigating 304 twin pairs, Study 2 showed that global narcissism
      and its two components, adaptive and maladaptive narcissism, as well as the
      impulsive buying tendency were heritable. The study found, moreover, that the
      connections between global narcissism and impulsive buying, and between
      maladaptive narcissism and impulsive buying were genetically based. These
      findings not only establish a link between narcissism and impulsive buying but
      also help to identify the origins of the link. The present studies deepen our
      understanding of narcissism, impulsive buying, and their interrelationship. 

PMID- 26217249
TI  - Visual speech discrimination and identification of natural and synthetic
      consonant stimuli.
AB  - From phonetic features to connected discourse, every level of psycholinguistic
      structure including prosody can be perceived through viewing the talking face.
      Yet a longstanding notion in the literature is that visual speech perceptual
      categories comprise groups of phonemes (referred to as visemes), such as /p, b,
      m/ and /f, v/, whose internal structure is not informative to the visual speech
      perceiver. This conclusion has not to our knowledge been evaluated using a
      psychophysical discrimination paradigm. We hypothesized that perceivers can
      discriminate the phonemes within typical viseme groups, and that discrimination
      measured with d-prime (d') and response latency is related to visual stimulus
      dissimilarities between consonant segments. In Experiment 1, participants
      performed speeded discrimination for pairs of consonant-vowel spoken nonsense
      syllables that were predicted to be same, near, or far in their perceptual
      distances, and that were presented as natural or synthesized video. Near pairs
      were within-viseme consonants. Natural within-viseme stimulus pairs were
      discriminated significantly above chance (except for /k/-/h/). Sensitivity (d')
      increased and response times decreased with distance. Discrimination and
      identification were superior with natural stimuli, which comprised more phonetic
      information. We suggest that the notion of the viseme as a unitary perceptual
      category is incorrect. Experiment 2 probed the perceptual basis for visual speech
      discrimination by inverting the stimuli. Overall reductions in d' with inverted
      stimuli but a persistent pattern of larger d' for far than for near stimulus
      pairs are interpreted as evidence that visual speech is represented by both its
      motion and configural attributes. The methods and results of this investigation
      open up avenues for understanding the neural and perceptual bases for visual and
      audiovisual speech perception and for development of practical applications such
      as visual lipreading/speechreading speech synthesis. 

PMID- 26217250
TI  - Navigation strategies as revealed by error patterns on the Magic Carpet test in
      children with cerebral palsy.
AB  - INTRODUCTION: Short-term memory develops differently in navigation vs. manual
      space. The Magic Carpet (MC) is a novel navigation test derived from the Walking
      Corsi Test and the manual Corsi Block-tapping Task (CBT). The MC requires mental
      rotations and executive function. In Cerebral Palsy (CP), CBT, and MC scores
      relate differently to clinical and lesional factors. Hypotheses of this study
      are: that frontal lesion specifically affect navigation in CP; that brain lesions
      affect MC cognitive strategies. MATERIALS AND METHODS: Twenty-two children with
      spastic CP, aged 5 to 14 years, 14 with a unilateral and 8 with a bilateral form,
      underwent the CBT and the MC. Errors were classified into seven patterns by a
      recently described algorithm. Brain lesions were quantified according to a novel
      semi-quantitative MRI scale. Control data were partially drawn from a previous
      study on 91 typically developing children. RESULTS: Children with CP performed
      worse than controls on both tests. Right hemispheric impairment correlated with
      spatial memory. MC span was reduced less than CBT span and was more selectively
      related to right middle white-matter and frontal lesions. Error patterns were
      differently distributed in CP and in typical development, and depended on right
      brain impairment: children with more extensive right lesions made more positional
      than sequential errors. DISCUSSION: In CP, navigation is affected especially by
      extensive lesions involving the right frontal lobe. In addition, these are
      associated with abnormal cognitive strategies. Whereas in typical development
      positional errors, preserving serial order, increase with age and performance, in
      CP they are associated with poorer performance and more extensive right-brain
      lesions. The explanation may lie in lesion side: right brain is crucial for
      mental rotations, necessary for spatial updating. Left-lateralized spatial memory
      strategies, relying on serial order, are not efficient if not accompanied by
      right-brain spatial functions.

PMID- 26217252
TI  - Relations between affective music and speech: evidence from dynamics of affective
      piano performance and speech production.
AB  - This study compares affective piano performance with speech production from the
      perspective of dynamics: unlike previous research, this study uses finger force
      and articulatory effort as indexes reflecting the dynamics of affective piano
      performance and speech production respectively. Moreover, for the first time
      physical constraints such as piano fingerings and speech articulatory constraints
      are included due to their potential contribution to different patterns of
      dynamics. A piano performance experiment and speech production experiment were
      conducted in four emotions: anger, fear, happiness and sadness. The results show
      that in both piano performance and speech production, anger and happiness
      generally have high dynamics while sadness has the lowest dynamics. Fingerings
      interact with fear in the piano experiment and articulatory constraints interact
      with anger in the speech experiment, i.e., large physical constraints produce
      significantly higher dynamics than small physical constraints in piano
      performance under the condition of fear and in speech production under the
      condition of anger. Using production experiments, this study firstly supports
      previous perception studies on relations between affective music and speech.
      Moreover, this is the first study to show quantitative evidence for the
      importance of considering motor aspects such as dynamics in comparing music
      performance and speech production in which motor mechanisms play a crucial role. 

PMID- 26217253
TI  - Turn-taking: a case study of early gesture and word use in answering WHERE and
      WHICH questions.
AB  - When young children answer questions, they do so more slowly than adults and
      appear to have difficulty finding the appropriate words. Because children leave
      gaps before they respond, it is possible that they could answer faster with
      gestures than with words. In this study, we compare gestural and verbal responses
      from one child between the ages of 1;4 and 3;5, to adult Where and Which
      questions, which can be answered with gestures and/or words. After extracting all
      adult Where and Which questions and child answers from longitudinal videotaped
      sessions, we examined the timing from the end of each question to the start of
      the response, and compared the timing for gestures and words. Child responses
      could take the form of a gesture or word(s); the latter could be words repeated
      from the adult question or new words retrieved by the child. Or responses could
      be complex: a gesture + word repeat, gesture + new word, or word repeat + new
      word. Gestures were the fastest overall, followed successively by word-repeats,
      then new-word responses. This ordering, with gestures ahead of words, suggests
      that the child knows what to answer but needs more time to retrieve any relevant
      words. In short, word retrieval and articulation appear to be bottlenecks in the
      timing of responses: both add to the planning required in answering a question. 

PMID- 26217254
TI  - Inductive generalization with familiar categories: developmental changes in
      children's reliance on perceptual similarity and kind information.
AB  - Inductive generalization is ubiquitous in human cognition; however, the factors
      underpinning this ability early in development remain contested. The present
      study was designed to (1) test the predictions of the naive theory and a
      similarity-based account and (2) examine the mechanism by which labels promote
      induction. In Experiment 1, 3- to 5-year-old children made inferences about
      highly familiar categories. The results were not fully consistent with either
      theoretical account. In contrast to the predictions of the naive theory approach,
      the youngest children in the study did not ignore perceptually compelling lures
      in favor of category-match items; in contrast to the predictions of the
      similarity-based account, no group of participants favored perceptually
      compelling lures in the presence of dissimilar-looking category-match items. In
      Experiment 2 we investigated the mechanisms by which labels promote induction by
      examining the influence of different label types, namely category labels (e.g.,
      the target and category-match both labeled as bird) and descriptor labels (e.g.,
      the target and the perceptual lure both labeled as brown) on induction
      performance. In contrast to the predictions of the naive theory approach,
      descriptor labels but not category labels affected induction in 3-year-old
      children. Consistent with the predictions of the similarity-based account,
      descriptor labels affected the performance of children in all age groups included
      in the study. The implications of these findings for the developmental account of
      induction are discussed. 

PMID- 26217255
TI  - Is there a universal answering strategy for rejecting negative propositions?
      Typological evidence on the use of prosody and gesture.
AB  - Previous research has proposed that languages diverge with respect to how their
      speakers confirm and contradict negative questions. Taking into account the
      classification between truth-based and polarity-based languages, this paper is
      mainly concerned with the expression of REJECT (a semantic operation that signals
      a contradiction move with respect to the common ground, along Krifka's lines) in
      two languages belonging to two typologically distinct answering systems, namely
      Catalan (polarity-based) and Russian (a mixed system using polarity-based, truth
      based, and echoic strategies). This investigation has two goals. First, to assess
      empirically the relevance of prosodic and gestural patterns in the interpretation
      of confirming and rejecting responses to negative polar questions. Second, to
      test the claim that in fact speakers resort to strikingly similar universal
      strategies at the time of expressing rejecting answers to discourse accessible
      negative assertions and negative polar questions, namely the use of linguistic
      units that encode REJECT in combination with ASSERT. The results of our
      investigation support the existence of a universal answering system for rejecting
      negative polar questions that integrates lexical and syntactic strategies with
      prosodic and gestural patterns, and instantiate the REJECT and ASSERT operators.
      We will also discuss the implications these results have for the truth-based vs.
      polarity-based taxonomy. 

PMID- 26217256
TI  - The influence of stereotype threat on immigrants: review and meta-analysis.
AB  - In many regions around the world students with certain immigrant backgrounds
      underachieve in educational settings. This paper provides a review and meta
      analysis on one potential source of the immigrant achievement gap: stereotype
      threat, a situational predicament that may prevent students to perform up to
      their full abilities. A meta-analysis of 19 experiments suggests an overall mean
      effect size of 0.63 (random effects model) in support of stereotype threat
      theory. The results are complemented by moderator analyses with regard to
      circulation (published or unpublished research), cultural context (US versus
      Europe), age of immigrants, type of stereotype threat manipulation, dependent
      measures, and means for identification of immigrant status; evidence on the role
      of ethnic identity strength is reviewed. Theoretical and practical implications
      of the findings are discussed. 

PMID- 26217257
TI  - Disambiguating ambiguous motion perception: what are the cues?
AB  - Motion perception is a fundamental feature of the human visual system. As part of
      our daily life we often have to determine the direction of motion, even in
      ambiguous (AMB) situations. These situations force us to rely on exogenous cues,
      such as other environmental motion, and endogenous cues, such as our own actions,
      or previously learned experiences. In three experiments, we asked participants to
      report the direction of an AMB motion display, while manipulating exogenous and
      endogenous sources of information. Specifically, in all three experiments the
      exogenous information was represented by another motion cue while the endogenous
      cue was represented, respectively, by movement execution, movement planning, or a
      learned association about the motion display. Participants were consistently
      biased by less AMB motion cues in the environment when reporting the AMB target
      direction. In the absence of less AMB exogenous motion information, participants
      were biased by their motor movements and even the planning of such movements.
      However, when participants learned a specific association about the target
      motion, this acquired endogenous knowledge countered exogenous motion cues in
      biasing participants' perception. Taken together, our findings demonstrate that
      we disambiguate AMB motion using different sources of exogenous and endogenous
      cues, and that learned associations may be particularly salient in countering the
      effects of environmental cues. 

PMID- 26217258
TI  - An algebraic topological method for multimodal brain networks comparisons.
AB  - Understanding brain connectivity is one of the most important issues in
      neuroscience. Nonetheless, connectivity data can reflect either functional
      relationships of brain activities or anatomical connections between brain areas.
      Although both representations should be related, this relationship is not
      straightforward. We have devised a powerful method that allows different
      operations between networks that share the same set of nodes, by embedding them
      in a common metric space, enforcing transitivity to the graph topology. Here, we
      apply this method to construct an aggregated network from a set of functional
      graphs, each one from a different subject. Once this aggregated functional
      network is constructed, we use again our method to compare it with the structural
      connectivity to identify particular brain regions that differ in both modalities
      (anatomical and functional). Remarkably, these brain regions include functional
      areas that form part of the classical resting state networks. We conclude that
      our method -based on the comparison of the aggregated functional network- reveals
      some emerging features that could not be observed when the comparison is
      performed with the classical averaged functional network. 

PMID- 26217260
TI  - Sub-optimal presentation of painful facial expressions enhances readiness for
      action and pain perception following electrocutaneous stimulation.
AB  - Observation of others' painful facial expressions has been shown to facilitate
      behavioral response tendencies and to increase pain perception in the observer.
      However, in previous studies, expressions were clearly visible to the observer
      and none of those studies investigated the effect of presence of peripheral
      stimulation on response tendencies. This study focuses on the effect of sub
      optimal presentation of painful facial expressions in the presence and absence of
      an electrocutaneous stimulus. Twenty-two healthy individuals categorized arrow
      targets which were preceded by a sub-optimally presented facial expression
      (painful, happy, or neutral in different blocks). On half of the trials, aversive
      electrocutaneous stimulation was delivered to the wrist of the non-dominant hand
      between the presentation of facial expression and target (an arrow directing to
      right or left). Participants' task was to indicate direction of the arrow as soon
      as it appears on the screen by pressing the corresponding key on the keyboard and
      to rate their pain at the end of block. Analysis showed that responses were
      faster to targets preceded by aversive stimulation than to targets not preceded
      by stimulation, especially following painful expressions. Painfulness ratings
      were higher following painful expressions than following happy expressions. These
      findings suggest that sub-optimally presented painful expressions can enhance
      readiness to act to neutral, non-pain-related targets after aversive stimulation
      and can increase pain perception. 

PMID- 26217259
TI  - The associations among the dopamine D2 receptor Taq1, emotional intelligence,
      creative potential measured by divergent thinking, and motivational state and
      these associations' sex differences.
AB  - Previous neuroscientific studies have shown that the dopaminergic system plays an
      important role in creative potential measured by divergent thinking (CPMDT),
      emotional control, and motivational state. However, although associations between
      two of these four components have been previously established (e.g., the
      association between CPMDT and emotional control, the association between CPMDT
      and motivational state, etc.), the interactions between these four remain
      unknown. The purpose of this study was to reveal these interactions using path
      analyses. The Taq1A polymorphism of the dopamine D2 receptor (DRD2) gene was used
      for this purpose. For measuring emotional intelligence (EI), we used the Japanese
      version of the Emotional Intelligence Scale. CPMDT was measured using the S-A
      creativity test. Motivational state was measured using the Vigor subscale of the
      Japanese version of the Profile of Mood Scale (POMS). Data from 766 healthy,
      right-handed individuals (426 men and 340 women; 20.7 +/- 1.9 years of age) were
      used in this study. There were significant and robust positive relationships
      among measures of CPMDT, EI, and motivational state across sex. In addition, the
      polymorphism of the DRD2 gene was significantly associated with EI, specifically
      in females. Path analysis in females indicates that the model in which (a) the
      DRD2 polymorphism primarily facilitates EI, (b) EI in turn facilitates CPMDT and
      leads to a better motivational state, and (c) a better motivational state also
      directly facilitates CPMDT explains the data in the most accurate manner. This
      study suggested a comprehensive picture of the cascade of the associations among
      dopamine, EI, motivational state, and CPMDT at least in females. 

PMID- 26217262
TI  - How basic-level objects facilitate question-asking in a categorization task.
AB  - The ability to categorize information is essential to everyday tasks such as
      identifying the cause of an event given a set of likely explanations or
      pinpointing the correct from a set of possible diagnoses by sequentially probing
      questions. In three studies, we investigated how the level of inclusiveness at
      which objects are presented (basic-level vs. subordinate-level) influences
      children's (7- and 10-year-olds) and adults' performance in a sequential binary
      categorization task. Study 1 found a robust facilitating effect of basic-level
      objects on the ability to ask effective questions in a computerized version of
      the Twenty Questions game. Study 2 suggested that this facilitating effect might
      be due to the kinds of object-differentiating features participants generate when
      provided with basic-level as compared to subordinate-level objects. Study 3 ruled
      out the alternative hypothesis that basic-level objects facilitate the selection
      of the most efficient among a given set of features. 

PMID- 26217261
TI  - Prior task experience affects temporal prediction and estimation.
AB  - It has been shown that prior experience with a task improves temporal prediction,
      even when the amount of prior experience with the task is often limited. The
      present study targeted the role of extensive training on temporal prediction.
      Expert and intermediate runners had to predict the time of a 5 km running
      competition. Furthermore, after the race's completion, participants had to
      estimate their running time so that it could be compared with the predicted time.
      Results show that expert runners were more accurate than intermediate runners for
      both predicting and estimating their running time. Furthermore, only expert
      runners had an estimation that was more accurate than their initial prediction.
      The results confirm the role of prior task experience in both temporal prediction
      and estimation. 

PMID- 26217263
TI  - The effect of meditation on regulation of internal body states.
AB  - Meditation is commonly thought to induce physiologically quiescent states, as
      evidenced by decreased autonomic parameters during the meditation practice
      including reduced heart rate, respiratory rate, blood pressure, skin conductance,
      and increased alpha activity in the electroencephalogram. Preliminary empirical
      support for this idea was provided in a case report by Dimsdale and Mills (2002),
      where it was found that meditation seemed to regulate increased levels of
      cardiovascular arousal induced by bolus isoproterenol infusions. In that study,
      while meditating, a self-taught meditator exhibited unexpected decreases in heart
      rate while receiving moderate intravenous doses of the beta adrenergic agonist
      isoproterenol. This effect was no longer observed when the individual received
      isoproterenol infusions while not meditating. The current study was designed to
      explore this phenomenon empirically in a group of formally trained meditators. A
      total of 15 meditators and 15 non-meditators individually matched on age, sex,
      and body mass index were recruited. Participants received four series of
      infusions in a pseudorandomized order: isoproterenol while meditating (or during
      a relaxation condition for the non-meditators), isoproterenol while resting,
      saline while meditating (or during a relaxation condition for the non
      meditators), and saline while resting. Heart rate was continuously measured
      throughout all infusions, and several measures of heart rate were derived from
      the instantaneous cardiac waveform. There was no evidence at the group or
      individual level suggesting that meditation reduced the cardiovascular response
      to isoproterenol, across all measures. These results suggest that meditation is
      not associated with increased regulation of elevated cardiac adrenergic tone. 

PMID- 26217264
TI  - State- or trait-like individual differences in dream recall: preliminary findings
      from a within-subjects study of multiple nap REM sleep awakenings.
AB  - We examined the question whether the role of EEG oscillations in predicting
      presence/absence of dream recall (DR) is explained by "state-" or "trait-like"
      factors. Six healthy subjects were awakened from REM sleep in a within-subjects
      design with multiple naps, until a recall and a non-recall condition were
      obtained. Naps were scheduled in the early afternoon and were separated by 1
      week. Topographical EEG data of the 5-min of REM sleep preceding each awakening
      were analyzed by power spectral analysis [Fast Fourier Transform (FFT)] and by a
      method to detect oscillatory activity [Better OSCillations (BOSC)]. Both analyses
      show that REC is associated to higher frontal theta activity (5-7 Hz) and theta
      oscillations (6.06 Hz) compared to NREC condition, but only the second comparison
      reached significance. Our pilot study provides support to the notion that sleep
      and wakefulness share similar EEG correlates of encoding in episodic memories,
      and supports the "state-like hypothesis": DR may depend on the physiological
      state related to the sleep stage from which the subject is awakened rather than
      on a stable individual EEG pattern. 

PMID- 26217265
TI  - What do we think we are doing: principles of coupled self-regulation in human
      robot interaction (HRI).

PMID- 26217266
TI  - Systematic analysis of video data from different human-robot interaction studies:
      a categorization of social signals during error situations.
AB  - Human-robot interactions are often affected by error situations that are caused
      by either the robot or the human. Therefore, robots would profit from the ability
      to recognize when error situations occur. We investigated the verbal and non
      verbal social signals that humans show when error situations occur in human-robot
      interaction experiments. For that, we analyzed 201 videos of five human-robot
      interaction user studies with varying tasks from four independent projects. The
      analysis shows that there are two types of error situations: social norm
      violations and technical failures. Social norm violations are situations in which
      the robot does not adhere to the underlying social script of the interaction.
      Technical failures are caused by technical shortcomings of the robot. The results
      of the video analysis show that the study participants use many head movements
      and very few gestures, but they often smile, when in an error situation with the
      robot. Another result is that the participants sometimes stop moving at the
      beginning of error situations. We also found that the participants talked more in
      the case of social norm violations and less during technical failures. Finally,
      the participants use fewer non-verbal social signals (for example smiling,
      nodding, and head shaking), when they are interacting with the robot alone and no
      experimenter or other human is present. The results suggest that participants do
      not see the robot as a social interaction partner with comparable communication
      skills. Our findings have implications for builders and evaluators of human-robot
      interaction systems. The builders need to consider including modules for
      recognition and classification of head movements to the robot input channels. The
      evaluators need to make sure that the presence of an experimenter does not skew
      the results of their user studies. 

PMID- 26217267
TI  - Action dynamics in multitasking: the impact of additional task factors on the
      execution of the prioritized motor movement.
AB  - In multitasking, the execution of a prioritized task is in danger of crosstalk by
      the secondary task. Task shielding allows minimizing this crosstalk. However, the
      locus and temporal dynamics of crosstalk effects and further sources of influence
      on the execution of the prioritized task are to-date only vaguely understood.
      Here we combined a dual-task paradigm with an action dynamics approach and
      studied how and according to which temporal characteristics crosstalk, previously
      experienced interference and previously executed responses influenced
      participants' mouse movements in the prioritized task's execution. Investigating
      continuous mouse movements of the prioritized task, our results indicate a
      continuous crosstalk from secondary task processing until the endpoint of the
      movement was reached, although the secondary task could only be executed after
      finishing execution of the prioritized task. The motor movement in the
      prioritized task was further modulated by previously experienced interference
      between the prioritized and the secondary task. Furthermore, response biases from
      previous responses of the prioritized and the secondary task in movements
      indicate different sources of such biases. The bias by previous responses to the
      prioritized task follows a sustained temporal pattern typical for a contextual
      reactivation, while the bias by previous responses to the secondary task follows
      a decaying temporal pattern indicating residual activation of previously
      activated spatial codes. 

PMID- 26217268
TI  - Stored object knowledge and the production of referring expressions: the case of
      color typicality.
AB  - When speakers describe objects with atypical properties, do they include these
      properties in their referring expressions, even when that is not strictly
      required for unique referent identification? Based on previous work, we predict
      that speakers mention the color of a target object more often when the object is
      atypically colored, compared to when it is typical. Taking literature from object
      recognition and visual attention into account, we further hypothesize that this
      behavior is proportional to the degree to which a color is atypical, and whether
      color is a highly diagnostic feature in the referred-to object's identity. We
      investigate these expectations in two language production experiments, in which
      participants referred to target objects in visual contexts. In Experiment 1, we
      find a strong effect of color typicality: less typical colors for target objects
      predict higher proportions of referring expressions that include color. In
      Experiment 2 we manipulated objects with more complex shapes, for which color is
      less diagnostic, and we find that the color typicality effect is moderated by
      color diagnosticity: it is strongest for high-color-diagnostic objects (i.e.,
      objects with a simple shape). These results suggest that the production of
      atypical color attributes results from a contrast with stored knowledge, an
      effect which is stronger when color is more central to object identification. Our
      findings offer evidence for models of reference production that incorporate
      general object knowledge, in order to be able to capture these effects of
      typicality on determining the content of referring expressions. 

PMID- 26217269
TI  - Commentary: Revisiting vocal perception in non-human animals: a review of vowel
      discrimination, speaker voice recognition, and speaker normalization.

PMID- 26217270
TI  - Does the transparency of the counting system affect children's numerical
      abilities?
AB  - The Welsh language uses a regular counting system, whereas English uses an
      irregular counting system, and schools within Wales teach either through the
      medium of Welsh or English. This provides the opportunity to compare linguistic
      effects on arithmetical skills in the absence of many other confounding factors
      that arise in international comparisons. This study investigated the hypothesis
      that language properties influence children's performance in certain numerical
      tasks by comparing the performance of 20 Welsh- and 20 English-medium Year Two
      pupils in non-verbal line estimations and transcoding. Groups did not differ on
      global arithmetic abilities, but the pupils taught through the medium of Welsh on
      average performed better in the non-verbal line estimation tasks than the English
      medium group. This superiority was most apparent in comparisons involving numbers
      over 20: a result which was complicated by the fact that Welsh-medium pupils
      showed a lower range of error scores than the English-medium pupils. These
      results were thought to be related to the increased transparency of the Welsh
      counting system. 

PMID- 26217271
TI  - Editorial: PsychOncology: clinical psychology for cancer patients-Cancer: the key
      role of clinical psychology.

PMID- 26217272
TI  - Organizational psychology on the way to 2065: a challenge to scholars.

PMID- 26217273
TI  - Investigating bias in squared regression structure coefficients.
AB  - The importance of structure coefficients and analogs of regression weights for
      analysis within the general linear model (GLM) has been well-documented. The
      purpose of this study was to investigate bias in squared structure coefficients
      in the context of multiple regression and to determine if a formula that had been
      shown to correct for bias in squared Pearson correlation coefficients and
      coefficients of determination could be used to correct for bias in squared
      regression structure coefficients. Using data from a Monte Carlo simulation, this
      study found that squared regression structure coefficients corrected with Pratt's
      formula produced less biased estimates and might be more accurate and stable
      estimates of population squared regression structure coefficients than estimates
      with no such corrections. While our findings are in line with prior literature
      that identified multicollinearity as a predictor of bias in squared regression
      structure coefficients but not coefficients of determination, the findings from
      this study are unique in that the level of predictive power, number of
      predictors, and sample size were also observed to contribute bias in squared
      regression structure coefficients. 

PMID- 26217274
TI  - Commentary: Large-scale psychological differences within China explained by rice
      vs. wheat agriculture.

PMID- 26217275
TI  - Decision making from economic and signal detection perspectives: development of
      an integrated framework.
AB  - Behavior is comprised of decisions made from moment to moment (i.e., to respond
      one way or another). Often, the decision maker cannot be certain of the value to
      be accrued from the decision (i.e., the outcome value). Decisions made under
      outcome value uncertainty form the basis of the economic framework of decision
      making. Behavior is also based on perception-perception of the external physical
      world and of the internal bodily milieu, which both provide cues that guide
      decision making. These perceptual signals are also often uncertain: another
      person's scowling facial expression may indicate threat or intense concentration,
      alternatives that require different responses from the perceiver. Decisions made
      under perceptual uncertainty form the basis of the signals framework of decision
      making. Traditional behavioral economic approaches to decision making focus on
      the uncertainty that comes from variability in possible outcome values, and
      typically ignore the influence of perceptual uncertainty. Conversely, traditional
      signal detection approaches to decision making focus on the uncertainty that
      arises from variability in perceptual signals and typically ignore the influence
      of outcome value uncertainty. Here, we compare and contrast the economic and
      signals frameworks that guide research in decision making, with the aim of
      promoting their integration. We show that an integrated framework can expand our
      ability to understand a wider variety of decision-making behaviors, in particular
      the complexly determined real-world decisions we all make every day. 

PMID- 26217276
TI  - The time course of emotional picture processing: an event-related potential study
      using a rapid serial visual presentation paradigm.
AB  - The present study recorded event-related potentials using rapid serial visual
      presentation paradigm to explore the time course of emotionally charged pictures.
      Participants completed a dual-target task as quickly and accurately as possible,
      in which they were asked to judge the gender of the person depicted (task 1) and
      the valence (positive, neutral, or negative) of the given picture (task 2). The
      results showed that the amplitudes of the P2 component were larger for emotional
      pictures than they were for neutral pictures, and this finding represents brain
      processes that distinguish emotional stimuli from non-emotional stimuli.
      Furthermore, positive, neutral, and negative pictures elicited late positive
      potentials with different amplitudes, implying that the differences between
      emotions are recognized. Additionally, the time course for emotional picture
      processing was consistent with the latter two stages of a three-stage model
      derived from studies on emotional facial expression processing and emotional
      adjective processing. The results of the present study indicate that in the three
      stage model of emotion processing, the middle and late stages are more universal
      and stable, and thus occur at similar time points when using different stimuli
      (faces, words, or scenes). 

PMID- 26217277
TI  - Executive and semantic processes in reappraisal of negative stimuli: insights
      from a meta-analysis of neuroimaging studies.
AB  - Neuroimaging investigations have identified the neural correlates of reappraisal
      in executive areas. These findings have been interpreted as evidence for
      recruitment of controlled processes, at the expense of automatic processes when
      responding to emotional stimuli. However, activation of semantic areas has also
      been reported. The aim of the present work was to address the issue of the
      importance of semantic areas in emotion regulation by comparing recruitment of
      executive and semantic neural substrates in studies investigating different
      reappraisal strategies. With this aim, we reviewed neuroimaging studies on
      reappraisal and we classified them in two main categories: reappraisal of stimuli
      (RS) and reappraisal via perspective taking (RPT). We applied a coordinate-based
      meta-analysis to summarize the results of fMRI studies on different reappraisal
      strategies. Our results showed that reappraisal, when considered regardless of
      the specific instruction used in the studies, involved both executive and
      semantic areas of the brain. When considering different reappraisal strategies
      separately, in contrast, we found areas associated with executive function to be
      prominently recruited by RS, even if also semantic areas were activated. Instead,
      in RPT the most important clusters of brain activity were found in parietal and
      temporal semantic areas, without significant clusters in executive areas. These
      results indicate that modulation of activity in semantic areas may constitute an
      important aspect of emotion regulation in reappraisal, suggesting that semantic
      processes may be more important to understand the mechanism of emotion regulation
      than previously thought. 

PMID- 26217279
TI  - "Bad boys don't cry": a thematic analysis of interpersonal dynamics in interview
      narratives of young offenders with psychopathic traits.
AB  - Most discussions of the social and interpersonal styles in individuals with
      strong psychopathic traits focus on their dangerousness or their affective and
      interpersonal deficiencies. This study has a different focus, and starts from the
      idea that such focus on the threat emanating from individuals with a psychopathic
      style might blind us from the logic inherent to their way of relating with the
      world. By means of a qualitative analysis (thematic analysis) of narratives from
      a Lacanian talking therapy, this study examines how 15 youngsters with strong
      psychopathic traits make sense of interpersonal events and relations. The main
      recurring theme across these narratives was that others in general are
      fundamentally distrustful antagonists that they have to protect themselves from.
      Especially the father figure, with whom identification seems to take place, is
      seen as a violent actor. Consequently, these youngsters develop multiple
      strategies of dealing with the threat they experience in relation to
      (significant) others. These relationship patterns also emerged within the
      therapeutic relationship, resulting in frequent testing of the therapist's
      trustworthiness. The results of this study, discussed in terms of Lacanian
      theory, might help therapists to develop treatment approaches that better fit
      with the interpersonal orientation of individuals with strong psychopathic
      traits. 

PMID- 26217278
TI  - Respiratory sensory gating measured by respiratory-related evoked potentials in
      generalized anxiety disorder.
AB  - The perception of respiratory sensations plays an important role both in
      respiratory diseases and in anxiety disorders. However, little is known about the
      neural processes underlying respiratory sensory perception, especially in patient
      groups. Therefore, the present study examined whether patients with generalized
      anxiety disorder (GAD) would demonstrate altered respiratory sensory gating
      compared to a healthy control group. Respiratory-related evoked potentials (RREP)
      were measured in a paired inspiratory occlusion paradigm presenting two brief
      occlusion stimuli (S1 and S2) within one inspiration. The results showed a
      significantly greater S2/S1 ratio for the N1 component of the RREP in the GAD
      group compared to the control group. Our findings suggest altered respiratory
      sensory processing in patients with GAD, which might contribute to altered
      perception of respiratory sensations in these patients. 

PMID- 26217280
TI  - The integration of emotional and symbolic components in multimodal communication.
AB  - Human multimodal communication can be said to serve two main purposes:
      information transfer and social influence. In this paper, I argue that different
      components of multimodal signals play different roles in the processes of
      information transfer and social influence. Although the symbolic components of
      communication (e.g., verbal and denotative signals) are well suited to transfer
      conceptual information, emotional components (e.g., non-verbal signals that are
      difficult to manipulate voluntarily) likely take a function that is closer to
      social influence. I suggest that emotion should be considered a property of
      communicative signals, rather than an entity that is transferred as content by
      non-verbal signals. In this view, the effect of emotional processes on
      communication serve to change the quality of social signals to make them more
      efficient at producing responses in perceivers, whereas symbolic components
      increase the signals' efficiency at interacting with the cognitive processes
      dedicated to the assessment of relevance. The interaction between symbolic and
      emotional components will be discussed in relation to the need for perceivers to
      evaluate the reliability of multimodal signals. 

PMID- 26217281
TI  - Exploring social influences on the joint Simon task: empathy and friendship.
AB  - Tasks for which people must act together to achieve a goal are a feature of daily
      life. The present study explored social influences on joint action using a Simon
      procedure for which participants (n = 44) were confronted with a series of images
      of hands and asked to respond via button press whenever the index finger wore a
      ring of a certain color (red or green) regardless of pointing direction (left or
      right). In an initial joint condition they performed the task while sitting next
      to another person (friend or stranger) who responded to the other color. In a
      subsequent individual condition they repeated the task on their own;
      additionally, they completed self-report tests of empathy. Consistent with past
      research, participants reacted more quickly when the finger pointed toward them
      rather than their co-actor (the Simon Effect or SE). The effect remained robust
      when the co-actor was no longer present and was unaffected by degree of
      acquaintance; however, its magnitude was correlated positively with empathy only
      among friends. For friends, the SE was predicted by cognitive perspective taking
      when the co-actor was present and by propensity for fantasizing when the co-actor
      was absent. We discuss these findings in relation to social accounts (e.g., task
      co-representation) and non-social accounts (e.g., referential coding) of joint
      action. 

PMID- 26217282
TI  - Cross-cultural comparison of motor competence in children from Australia and
      Belgium.
AB  - Motor competence in childhood is an important determinant of physical activity
      and physical fitness in later life. However, childhood competence levels in many
      countries are lower than desired. Due to the many different motor skill
      instruments in use, children's motor competence across countries is rarely
      compared. The purpose of this study was to evaluate the motor competence of
      children from Australia and Belgium using the Korperkoordinationstest fur Kinder
      (KTK). The sample consisted of 244 (43.4% boys) Belgian children and 252 (50.0%
      boys) Australian children, aged 6-8 years. A MANCOVA for the motor scores showed
      a significant country effect. Belgian children scored higher on jumping sideways,
      moving sideways and hopping for height but not for balancing backwards. Moreover,
      a Chi squared test revealed significant differences between the Belgian and
      Australian score distribution with 21.3% Belgian and 39.3% Australian children
      scoring "below average." The very low levels reported by Australian children may
      be the result of cultural differences in physical activity contexts such as
      physical education and active transport. When compared to normed scores, both
      samples scored significantly worse than children 40 years ago. The decline in
      children's motor competence is a global issue, largely influenced by increasing
      sedentary behavior and a decline in physical activity. 

PMID- 26217283
TI  - Metacognitive therapy (MCT+) in patients with psychosis not receiving
      antipsychotic medication: A case study.
AB  - BACKGROUND: Psychotherapies for psychosis typically aim to develop an awareness
      of the implausible content of a delusion or target the underlying cognitive
      biases (i.e., problematic thinking styles, such as hasty decisions and illusory
      control) that foster and maintain delusional beliefs. A recently designed
      individual-based treatment entitled metacognitive therapy (MCT+) combines these
      two approaches. Emerging evidence suggests individualized MCT+, when used
      concurrently with antipsychotic medication, may be an effective psychological
      treatment for reducing delusional symptoms. However, it remains to be tested
      whether MCT+ can be effective in patients with active delusions who are not
      currently receiving psychotropic drugs. METHOD: We present two cases (one patient
      with schizophrenia and the other with delusional disorder) experiencing active
      delusions who underwent 4-weeks of intensive MCT+, without concurrent
      antipsychotic medication (minimum 6-months unmedicated). Baseline and 6-week
      follow-up data are presented on a variety of measures assessing delusion symptom
      severity (i.e., PANSS, PSYRATS, SAPS), clinical insight, and cognitive bias
      propensity. RESULTS: After 4-weeks of MCT+, both patients showed substantial
      reduction in delusional symptoms, reported improved clinical insight, and were
      less prone to making illusory correlations. CONCLUSIONS: The presented case
      studies provide preliminary evidence for the feasibility of MCT+ in treating
      patients not taking, or resistant to, antipsychotic medication.

PMID- 26217284
TI  - An integrative review of attention biases and their contribution to treatment for
      anxiety disorders.
AB  - Models of exposure therapy, one of the key components of cognitive behavioral
      therapy for anxiety disorders, suggest that attention may play an important role
      in the extinction of fear and anxiety. Evidence from cognitive research suggests
      that individual differences may play a causal role in the onset and maintenance
      of anxiety disorders and so it is also likely to influence treatment. We review
      the evidence concerning attention and treatment outcomes in anxiety disorders.
      The evidence reviewed here suggests that that attention biases assessed at pre
      treatment might actually predict improved response to treatment, and in
      particular that prolonged engagement with threat as measured in tasks such as the
      dot probe is associated with greater reductions in anxious symptoms following
      treatment. We examine this research within a fear learning framework, considering
      the possible role of individual differences in attention in the extinction of
      fear during exposure. Theoretical, experimental and clinical implications are
      discussed, particularly with reference to the potential for attention bias
      modification programs in augmenting treatment, and also with reference to how
      existing research in this area might inform best practice for clinicians. 

PMID- 26217285
TI  - Face perception and processing in early infancy: inborn predispositions and
      developmental changes.
AB  - From birth it is critical for our survival to identify social agents and
      conspecifics. Among others stimuli, faces provide the required information. The
      present paper will review the mechanisms subserving face detection and face
      recognition, respectively, over development. In addition, the emergence of the
      functional and neural specialization for face processing as an experience
      dependent process will be documented. Overall, the present work highlights the
      importance of both inborn predispositions and the exposure to certain
      experiences, shortly after birth, to drive the system to become functionally
      specialized to process faces in the first months of life. 

PMID- 26217286
TI  - Basic auditory processing and sensitivity to prosodic structure in children with
      specific language impairments: a new look at a perceptual hypothesis.
AB  - Children with specific language impairments (SLIs) show impaired perception and
      production of spoken language, and can also present with motor, auditory, and
      phonological difficulties. Recent auditory studies have shown impaired
      sensitivity to amplitude rise time (ART) in children with SLIs, along with non
      speech rhythmic timing difficulties. Linguistically, these perceptual impairments
      should affect sensitivity to speech prosody and syllable stress. Here we used two
      tasks requiring sensitivity to prosodic structure, the DeeDee task and a stress
      misperception task, to investigate this hypothesis. We also measured auditory
      processing of ART, rising pitch and sound duration, in both speech ("ba") and non
      speech (tone) stimuli. Participants were 45 children with SLI aged on average 9
      years and 50 age-matched controls. We report data for all the SLI children (N =
      45, IQ varying), as well as for two independent SLI subgroupings with intact IQ.
      One subgroup, "Pure SLI," had intact phonology and reading (N = 16), the other,
      "SLI PPR" (N = 15), had impaired phonology and reading. Problems with syllable
      stress and prosodic structure were found for all the group comparisons. Both sub
      groups with intact IQ showed reduced sensitivity to ART in speech stimuli, but
      the PPR subgroup also showed reduced sensitivity to sound duration in speech
      stimuli. Individual differences in processing syllable stress were associated
      with auditory processing. These data support a new hypothesis, the "prosodic
      phrasing" hypothesis, which proposes that grammatical difficulties in SLI may
      reflect perceptual difficulties with global prosodic structure related to
      auditory impairments in processing amplitude rise time and duration. 

PMID- 26217287
TI  - Does conflict help or hurt cognitive control? Initial evidence for an inverted U
      shape relationship between perceived task difficulty and conflict adaptation.
AB  - Sequential modulation of congruency effects in conflict tasks indicates that
      cognitive control quickly adapts to changing task demands. We investigated in
      four experiments how this behavioral congruency-sequence effect relates to
      different levels of perceived task difficulty in a flanker and a Stroop task. In
      addition, online measures of pupil diameter were used as a physiological index of
      effort mobilization. Consistent with motivational accounts predicting that
      increased levels of perceived task difficulty will increase effort mobilization
      only up to a certain limit, reliable dynamic conflict-driven adjustment in
      cognitive control was only observed when task difficulty was relatively low.
      Instead, tasks tentatively associated with high levels of difficulty showed no or
      reversed conflict adaptation. Although the effects could not be linked
      consistently to effects in self-reported task difficulty in all experiments,
      regression analyses showed associations between perceived task difficulty and
      conflict adaptation in some of the experiments, which provides some initial
      evidence for an inverted U-shape relationship between perceived difficulty and
      adaptations in cognitive control. Furthermore, high levels of task difficulty
      were associated with a conflict-driven reduction in pupil dilation, suggesting
      that pupil dilation can be used as a physiological marker of mental overload. Our
      findings underscore the importance of developing models that are grounded in
      motivational accounts of cognitive control. 

PMID- 26217288
TI  - Emotional words can be embodied or disembodied: the role of superficial vs. deep
      types of processing.
AB  - Emotional words are processed rapidly and automatically in the left hemisphere
      (LH) and slowly, with the involvement of attention, in the right hemisphere (RH).
      This review aims to find the reason for this difference and suggests that
      emotional words can be processed superficially or deeply due to the involvement
      of the linguistic and imagery systems, respectively. During superficial
      processing, emotional words likely make connections only with semantically
      associated words in the LH. This part of the process is automatic and may be
      sufficient for the purpose of language processing. Deep processing, in contrast,
      seems to involve conceptual information and imagery of a word's perceptual and
      emotional properties using autobiographical memory contents. Imagery and the
      involvement of autobiographical memory likely differentiate between emotional and
      neutral word processing and explain the salient role of the RH in emotional word
      processing. It is concluded that the level of emotional word processing in the RH
      should be deeper than in the LH and, thus, it is conceivable that the slow mode
      of processing adds certain qualities to the output. 

PMID- 26217289
TI  - The role of emotionality in the acquisition of new concrete and abstract words.
AB  - A processing advantage for emotional words relative to neutral words has been
      widely demonstrated in the monolingual domain (e.g., Kuperman et al., 2014). It
      is also well-known that, in bilingual speakers who have a certain degree of
      proficiency in their second language, the effects of the affective content of
      words on cognition are not restricted to the native language (e.g., Ferre et al.,
      2010). The aim of the present study was to test whether this facilitatory effect
      can also be obtained during the very early stages of word acquisition. In the
      context of a novel word learning paradigm, participants were trained on a set of
      Basque words by associating them to their Spanish translations. Words'
      concreteness and affective valence were orthogonally manipulated. Immediately
      after the learning phase and 1 week later, participants were tested in a Basque
      go-no go lexical decision task as well as in a translation task in which they had
      to provide the Spanish translation of the Basque words. A similar pattern of
      results was found across tasks and sessions, revealing main effects of
      concreteness and emotional content as well as an interaction between both
      factors. Thus, the emotional content facilitated the acquisition of abstract, but
      not concrete words, in the new language, with a more reliable effect for negative
      words than for positive ones. The results are discussed in light of the embodied
      theoretical view of semantic representation proposed by Kousta et al. (2011). 

PMID- 26217290
TI  - Music and trauma: the relationship between music, personality, and coping style.

PMID- 26217291
TI  - Mental abilities and performance efficacy under a simulated 480-m helium-oxygen
      saturation diving.
AB  - Stress in extreme environment severely disrupts human physiology and mental
      abilities. The present study investigated the cognition and performance efficacy
      of four divers during a simulated 480 meters helium-oxygen saturation diving. We
      analyzed the spatial memory, 2D/3D mental rotation functioning, grip strength,
      and hand-eye coordination ability in four divers during the 0-480 m compression
      and decompression processes of the simulated diving. The results showed that
      except for its mild decrease on grip strength, the high atmosphere pressure
      condition significantly impaired the hand-eye coordination (especially above 300
      m), the reaction time and correct rate of mental rotation, as well as the spatial
      memory (especially as 410 m), showing high individual variability. We conclude
      that the human cognition and performance efficacy are significantly affected
      during deep water saturation diving. 

PMID- 26217292
TI  - A dance movement therapy group for depressed adult patients in a psychiatric
      outpatient clinic: effects of the treatment.
AB  - We were interested in investigating the effects of dance movement therapy (DMT)
      in a psychiatric outpatient clinic with patients diagnosed with depression. DMT
      aims to engage the patients in physical and verbal exploration of their
      experiences generated in movement based interaction. The assumption was that DMT,
      which includes both physical engagement as well as emotional and social
      exploration, would alleviate the mood and psychiatric symptoms. All adult
      patients (n = 33) included in the study received treatment as usual (TAU). Twenty
      one patients participated in a 12-session DMT group intervention, and the
      remaining 12 patients chose to take TAU only. The majority of the patients
      suffered from moderate or severe depression, recurrent and/or chronic type. The
      effects of the interventions were investigated after the intervention, and at 3
      month follow-up. Compared to the TAU, adding DMT seemed to improve the effect of
      the treatment. The effect of the DMT was observable whether the patient was
      taking antidepressant medication or not. At follow-up, between group effect sizes
      (ES) were medium in favor for the DMT group (d = 0.60-0.79). In the DMT group,
      the within ES at the 3 months follow-up varied from 0.62 to 0.82 as compared to
      TAU 0.15-0.37. The results indicated that DMT is beneficial in the treatment of
      depressed patients. 

PMID- 26217293
TI  - On the relationship between emotional state and abnormal unfairness sensitivity
      in alcohol dependence.
AB  - Recent empirical findings suggest that alcohol dependence is characterized by
      heightened sensitivity to unfairness during social transactions. The present
      study went a step further and aimed to ascertain whether this abnormal level of
      sensitivity to unfairness is underlined by an increased emotional reactivity.
      Twenty-six recently abstinent alcohol-dependent (AD) individuals and 32 controls
      performed an ultimatum game (UG), in which participants had to respond to take-it
      or-leave-it offers, ranging from fair to unfair and made by a fictive proposer.
      Emotional state was recorded during UG offers presentation and was indexed by the
      amplitude of skin conductance response (SCR). Results showed that AD decided to
      reject unfair offers more frequently than their controls, confirming previous
      data. The proportion of rejected unfair UG offers was correlated with SCR, in the
      AD but not in the control group. This finding suggests that deciding to accept or
      reject unfair UG offers is influenced by arousal-affective activity in AD, but
      not in controls. Heightened emotional reactivity may have driven AD to punish the
      proposer rather than acting as a rational economic agent. An implication of
      present findings is that AD might have difficult to cope with unfair situations
      triggered by social interactions. Future studies are needed in order to examine
      whether-emotional and behavioral-reactivity to unfairness during the UG could
      impact alcohol consumption and relapse in AD. 

PMID- 26217295
TI  - Erratum on: Follow the heart or the head? The interactive influence model of
      emotion and cognition.
AB  - [This corrects the article on p. 573 in vol. 6, PMID: 25999889.]. 

PMID- 26217294
TI  - Expertise and decision-making in American football.
AB  - In American football, pass interference calls can be difficult to make,
      especially when the timing of contact between players is ambiguous. American
      football history contains many examples of controversial pass interference
      decisions, often with fans, players, and officials interpreting the same event
      differently. The current study sought to evaluate the influence of experience
      with concepts important for officiating decisions in American football on the
      probability (i.e., response criteria) of pass interference calls. We further
      investigated the extent to which such experience modulates perceptual biases that
      might influence the interpretation of such events. We hypothesized that observers
      with less experience with the American football concepts important for pass
      interference would make progressively more pass interference calls than more
      experienced observers, even when given an explicit description of the necessary
      criteria for a pass interference call. In a go/no-go experiment using photographs
      from American football games, three groups of participants with different levels
      of experience with American football (Football Naive, Football Player, and
      Football Official) made pass interference calls for pictures depicting left
      moving and right-moving events. More experience was associated with progressively
      and significantly fewer pass interference calls [F (2,48) = 10.4, p < 0.001],
      with Football Naive participants making the most pass interference calls, and
      Football Officials the least. In addition, our data replicated a prior finding of
      spatial biases for interpreting left-moving images more harshly than identical
      right-moving images, but only in Football Players. These data suggest that
      experience with the concepts important for making a decision may influence the
      rate of decision-making, and may also play a role in susceptibility to spatial
      biases. 

PMID- 26217296
TI  - Toward a High-Resolution Neuroimaging Biomarker for Mild Traumatic Brain Injury:
      From Bench to Bedside.

PMID- 26217297
TI  - Paving the Way to Understand Autoantibody-Mediated Epilepsy on the Molecular
      Level.
AB  - Correct function of neuronal networks is enabled by a delicate interplay among
      neurons communicating with each other. One of the keys is the communication at
      chemical synapses where neurotransmitters like glutamate, GABA, and glycine
      enable signal transfer over the synaptic cleft. Thereby, the neurotransmitters
      are released from the presynapse and bind as ligands to specific receptors at the
      postsynaptic side to allow for modulation of the postsynaptic membrane
      potentials. The postsynaptic electrical signal, which is highly modulated by
      voltage-gated ion channels, spreads over the dendritic tree and is thus
      integrated to allow for generation of action potentials at the axon hillock. This
      concert of receptors and voltage-gated ion channels depends on correct function
      of all its components. Misfunction of receptors and/or voltage-gated potassium
      channels (VGKC) leads to diverse adverse effects in patients. Such malfunctions
      can be the result of inherited genetic alterations or pharmacological side
      effects by drugs. Recently, autoantibodies targeting receptor or channel
      complexes like NMDAR, AMPAR, GABA-receptors, glycine receptors, LGI1 or CASPR2
      (previously termed as VGKC-complex antibodies) have been discovered. The presence
      of specific autoantibodies against these targets associates with severe forms of
      antibody-mediated encephalitis. Understanding the molecular details of
      autoantibody actions on receptor and VGKC complexes is highly desirable and may
      open the path to develop specific therapies to treat humoral autoimmune
      encephalitis. Here, we summarize the current knowledge and discuss technical
      approaches to fill the gap of knowledge. These techniques include
      electrophysiology, biochemical approaches for epitope mapping, and in silico
      modeling to simulate molecular interactions between autoantibody and its
      molecular target. 

PMID- 26217298
TI  - Hemodynamic Signal Changes Accompanying Execution and Imagery of Swallowing in
      Patients with Dysphagia: A Multiple Single-Case Near-Infrared Spectroscopy Study.
AB  - In the present multiple case study, we examined hemodynamic changes in the brain
      in response to motor execution (ME) and motor imagery (MI) of swallowing in
      dysphagia patients compared to healthy matched controls using near-infrared
      spectroscopy (NIRS). Two stroke patients with cerebral lesions in the right
      hemisphere, two stroke patients with lesions in the brainstem, and two
      neurologically healthy control subjects actively swallowed saliva (ME) and
      mentally imagined to swallow saliva (MI) in a randomized order while changes in
      concentration of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin
      (deoxy-Hb) were assessed. In line with recent findings in healthy young adults,
      MI and ME of swallowing led to the strongest NIRS signal change in the inferior
      frontal gyrus in stroke patients as well as in healthy elderly. We found
      differences in the topographical distribution and time course of the hemodynamic
      response in dependence on lesion location. Dysphagia patients with lesions in the
      brainstem showed bilateral hemodynamic signal changes in the inferior frontal
      gyrus during active swallowing comparable to healthy controls. In contrast,
      dysphagia patients with cerebral lesions in the right hemisphere showed more
      unilateral activation patterns during swallowing. Furthermore, patients with
      cerebral lesions showed a prolonged time course of the hemodynamic response
      during MI and ME of swallowing compared to healthy controls and patients with
      brainstem lesions. Brain activation patterns associated with ME and MI of
      swallowing were largely comparable, especially for changes in deoxy-Hb. Hence,
      the present results provide new evidence regarding timing and topographical
      distribution of the hemodynamic response during ME and MI of swallowing in
      dysphagia patients and may have practical impact on future dysphagia treatment. 

PMID- 26217299
TI  - Mild Cognitive Impairment: Structural, Metabolical, and Neurophysiological
      Evidence of a Novel EEG Biomarker.
AB  - BACKGROUND: Recent studies demonstrate that the alpha3/alpha2 power ratio
      correlates with cortical atrophy, regional hypoperfusion, and memory impairment
      in subjects with mild cognitive impairment (MCI). METHODS: Evidences were
      reviewed in subjects with MCI, who underwent EEG recording, magnetic resonance
      imaging (MRI) scans, and memory evaluation. Alpha3/alpha2 power ratio (alpha2 8.9
      10.9 Hz range; alpha3 10.9-12.9 Hz range), cortical thickness, linear EEG
      coherence, and memory impairment have been evaluated in a large group of 74
      patients. A subset of 27 subjects within the same group also underwent single
      photon emission computed tomography (SPECT) evaluation. RESULTS: In MCI subjects
      with higher EEG upper/low alpha power ratio, a greater temporo-parietal and
      hippocampal atrophy was found as well as a decrease in regional blood perfusion
      and memory impairment. In this group, an increase of theta oscillations is
      associated with a greater interhemispheric coupling between temporal areas.
      CONCLUSION: The increase of alpha3/alpha2 power ratio is a promising novel
      biomarker in identifying MCI subjects at risk for Alzheimer's disease.

PMID- 26217300
TI  - Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD
      Biomarkers.
AB  - INTRODUCTION: Core cerebrospinal fluid (CSF) biomarkers - Abeta42, Tau, and
      phosphorylated Tau (pTau) - have been recently incorporated in the revised
      criteria for Alzheimer's disease (AD). However, their widespread clinical
      application lacks standardization. Pre-analytical sample handling and storage
      play an important role in the reliable measurement of these biomarkers across
      laboratories. AIM: In this study, we aim to surpass the efforts from previous
      studies, by employing a multicenter approach to assess the impact of less studied
      CSF pre-analytical confounders in AD-biomarkers quantification. METHODS: Four
      different centers participated in this study and followed the same established
      protocol. CSF samples were analyzed for three biomarkers (Abeta42, Tau, and pTau)
      and tested for different spinning conditions [temperature: room temperature (RT)
      vs. 4 degrees C; speed: 500 vs. 2000 vs. 3000 g], storage volume variations (25,
      50, and 75% of tube total volume), as well as freezing-thaw cycles (up to five
      cycles). The influence of sample routine parameters, inter-center variability,
      and relative value of each biomarker (reported as normal/abnormal) was analyzed.
      RESULTS: Centrifugation conditions did not influence biomarkers levels, except
      for samples with a high CSF total protein content, where either non
      centrifugation or centrifugation at RT, compared to 4 degrees C, led to higher
      Abeta42 levels. Reducing CSF storage volume from 75 to 50% of total tube capacity
      decreased Abeta42 concentration (within analytical CV of the assay), whereas no
      change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau
      appears to be stable up to five freeze-thaw cycles, whereas Abeta42 levels
      decrease if CSF is freeze-thawed more than three times. CONCLUSION: This
      systematic study reinforces the need for CSF centrifugation at 4 degrees C prior
      to storage and highlights the influence of storage conditions in Abeta42 levels.
      This study contributes to the establishment of harmonized standard operating
      procedures that will help reducing inter-lab variability of CSF-AD biomarkers
      evaluation.

PMID- 26217301
TI  - The Video Head Impulse Test (vHIT) of Semicircular Canal Function - Age-Dependent
      Normative Values of VOR Gain in Healthy Subjects.
AB  - BACKGROUND/HYPOTHESIS: The video Head Impulse Test (vHIT) is now widely used to
      test the function of each of the six semicircular canals individually by
      measuring the eye rotation response to an abrupt head rotation in the plane of
      the canal. The main measure of canal adequacy is the ratio of the eye movement
      response to the head movement stimulus, i.e., the gain of the vestibulo-ocular
      reflex (VOR). However, there is a need for normative data about how VOR gain is
      affected by age and also by head velocity, to allow the response of any
      particular patient to be compared to the responses of healthy subjects in their
      age range. In this study, we determined for all six semicircular canals,
      normative values of VOR gain, for each canal across a range of head velocities,
      for healthy subjects in each decade of life. STUDY DESIGN: The VOR gain was
      measured for all canals across a range of head velocities for at least 10 healthy
      subjects in decade age bands: 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80
      89. METHODS: The compensatory eye movement response to a small, unpredictable,
      abrupt head rotation (head impulse) was measured by the ICS impulse prototype
      system. The same operator delivered every impulse to every subject. RESULTS:
      Vestibulo-ocular reflex gain decreased at high head velocities, but was largely
      unaffected by age into the 80- to 89-year age group. There were some small but
      systematic differences between the two directions of head rotation, which appear
      to be largely due to the fact that in this study only the right eye was measured.
      The results are considered in relation to recent evidence about the effect of age
      on VOR performance. CONCLUSION: These normative values allow the results of any
      particular patient to be compared to the values of healthy people in their age
      range and so allow, for example, detection of whether a patient has a bilateral
      vestibular loss. VOR gain, as measured directly by the eye movement response to
      head rotation, seems largely unaffected by aging.

PMID- 26217302
TI  - Image More to Save More.
AB  - Recent successful endovascular stroke trials have provided unequivocal support
      for these therapies in selected patients with large-vessel occlusive acute
      ischemic stroke. In this piece, we briefly review these trials and their
      utilization of advanced neuroimaging techniques that played a pivotal role in
      their success through targeted patient selection. In this context, the unique
      challenges and opportunity for advancement in current stroke networks' routine
      delivery of care created by these trials are discussed and recommendations to
      change current national stroke system guidelines are proposed. 

PMID- 26217303
TI  - Young Women do it Better: Sexual Dimorphism in Temporal Discrimination.
AB  - The temporal discrimination threshold (TDT) is the shortest time interval at
      which two sensory stimuli presented sequentially are detected as asynchronous by
      the observer. TDTs are known to increase with age. Having previously observed
      shorter thresholds in young women than in men, in this work we sought to
      systematically examine the effect of sex and age on temporal discrimination. The
      aims of this study were to examine, in a large group of men and women aged 20-65
      years, the distribution of TDTs with an analysis of the individual participant's
      responses, assessing the "point of subjective equality" and the "just noticeable
      difference" (JND). These respectively assess sensitivity and accuracy of an
      individual's response. In 175 participants (88 women) aged 20-65 years, temporal
      discrimination was faster in women than in men under the age of 40 years by a
      mean of approximately 13 ms. However, age-related decline in temporal
      discrimination was three times faster in women so that, in the age group of 40-65
      years, the female superiority was reversed. The point of subjective equality
      showed a similar advantage in younger women and more marked age-related decline
      in women than men, as the TDT. JND values declined equally in both sexes, showing
      no sexual dimorphism. This observed sexual dimorphism in temporal discrimination
      is important for both (a) future clinical research assessing disordered mid-brain
      covert attention in basal-ganglia disorders, and (b) understanding the biology of
      this sexual dimorphism which may be genetic or hormonal. 

PMID- 26217305
TI  - microRNA-Based Biomarkers and the Diagnosis of Alzheimer's Disease.

PMID- 26217304
TI  - Manganese-Enhanced MRI: Biological Applications in Neuroscience.
AB  - Magnetic resonance imaging (MRI) is an excellent non-invasive tool to investigate
      biological systems. The administration of the paramagnetic divalent ion manganese
      (Mn(2+)) enhances MRI contrast in vivo. Due to similarities between Mn(2+) and
      calcium (Ca(2+)), the premise of manganese-enhanced MRI (MEMRI) is that the
      former may enter neurons and other excitable cells through voltage-gated Ca(2+)
      channels. As such, MEMRI has been used to trace neuronal pathways, define
      morphological boundaries, and study connectivity in morphological and functional
      imaging studies. In this article, we provide a brief overview of MEMRI and
      discuss recently published data to illustrate the usefulness of this method,
      particularly in animal models. 

PMID- 26217306
TI  - A Subset of Nuclear Receptors are Uniquely Expressed in Uveal Melanoma Cells.
AB  - Uveal melanoma (UM) is recognized as the most common intraocular malignancy and
      the second most common form of melanoma. Nearly 50% of UM patients develop
      untreatable and fatal metastases. The 48-member nuclear receptor (NR) superfamily
      represents a therapeutically targetable group of transcription factors known for
      their regulation of key cancer pathways in numerous tumor types. Here, we
      profiled the expression of the 48 human NRs by qRT-PCR across a melanoma cell
      line panel including 5 UM lines, 9 cutaneous melanoma (CM) lines, and normal
      primary melanocytes. NR expression patterns identified a few key features. First,
      in agreement with our past studies identifying RXRg as a CM-specific marker, we
      found that UM cells also exhibit high levels of RXRg expression, making it a
      universal biomarker for melanoma tumors. Second, we found that LXRb is highly
      expressed in both UM and CM lines, suggesting that it may be a therapeutic target
      in a UM metastatic setting as it has been in CM models. Third, we found that
      RARg, PPARd, EAR2, RXRa, and TRa expressions could subdivide UM from CM. Previous
      studies of UM cancers identified key mutations in three genes: GNAQ, GNA11, and
      BRAF. We found unique NR expression profiles associated with each of these UM
      mutations. We then performed NR-to-NR and NR-to-genome expression correlation
      analyses to find potential NR-driven transcriptional programs activated in UM and
      CM. Specifically, RXRg controlled gene networks were identified that may drive
      melanoma-specific signaling and metabolism. ERRa was identified as a UM-defining
      NR and genes correlated with its expression confirm the role of ERRa in metabolic
      control. Given the plethora of available NR agonists, antagonists, and selective
      receptor modulators, pharmacologic manipulation of these NRs and their
      transcriptional outputs may lead to a more comprehensive understanding of key UM
      pathways and how we can leverage them for better therapeutic alternatives. 

PMID- 26217307
TI  - Ligand-Binding Affinity at the Insulin Receptor Isoform-A and Subsequent IR-A
      Tyrosine Phosphorylation Kinetics are Important Determinants of Mitogenic
      Biological Outcomes.
AB  - The insulin receptor (IR) is a tyrosine kinase receptor that can mediate both
      metabolic and mitogenic biological actions. The IR isoform-A (IR-A) arises from
      alternative splicing of exon 11 and has different ligand binding and signaling
      properties compared to the IR isoform-B. The IR-A not only binds insulin but also
      insulin-like growth factor-II (IGF-II) with high affinity. IGF-II acting through
      the IR-A promotes cancer cell proliferation, survival, and migration by
      activating some unique signaling molecules compared to those activated by
      insulin. This observation led us to investigate whether the different IR-A
      signaling outcomes in response to IGF-II and insulin could be attributed to
      phosphorylation of a different subset of IR-A tyrosine residues or to the
      phosphorylation kinetics. We correlated IR-A phosphorylation to activation of
      molecules involved in mitogenic and metabolic signaling (MAPK and Akt) and
      receptor internalization rates (related to mitogenic signaling). We also extended
      this study to incorporate two ligands that are known to promote predominantly
      mitogenic [(His(4), Tyr(15), Thr(49), Ile(51)) IGF-I, qIGF-I] or metabolic (S597
      peptide) biological actions, to see if common mechanisms can be used to define
      mitogenic or metabolic signaling through the IR-A. The threefold lower mitogenic
      action of IGF-II compared to insulin was associated with a decreased potency in
      activation of Y960, Y1146, Y1150, Y1151, Y1316, and Y1322, in MAPK
      phosphorylation and in IR-A internalization. With the poorly mitogenic S597
      peptide, it was a decreased rate of tyrosine phosphorylation rather than potency
      that was associated with a low mitogenic potential. We conclude that both
      decreased affinity of IR-A binding and kinetics of IR-A phosphorylation can
      independently lead to a lower mitogenic activity. None of the studied parameters
      could account for the lower metabolic activity of qIGF-I. 

PMID- 26217308
TI  - Distinct soil bacterial communities along a small-scale elevational gradient in
      alpine tundra.
AB  - The elevational diversity pattern for microorganisms has received great attention
      recently but is still understudied, and phylogenetic relatedness is rarely
      studied for microbial elevational distributions. Using a bar-coded pyrosequencing
      technique, we examined the biodiversity patterns for soil bacterial communities
      of tundra ecosystem along 2000-2500 m elevations on Changbai Mountain in China.
      Bacterial taxonomic richness displayed a linear decreasing trend with increasing
      elevation. Phylogenetic diversity and mean nearest taxon distance (MNTD)
      exhibited a unimodal pattern with elevation. Bacterial communities were more
      phylogenetically clustered than expected by chance at all elevations based on the
      standardized effect size of MNTD metric. The bacterial communities differed
      dramatically among elevations, and the community composition was significantly
      correlated with soil total carbon (TC), total nitrogen, C:N ratio, and dissolved
      organic carbon. Multiple ordinary least squares regression analysis showed that
      the observed biodiversity patterns strongly correlated with soil TC and C:N
      ratio. Taken together, this is the first time that a significant bacterial
      diversity pattern has been observed across a small-scale elevational gradient.
      Our results indicated that soil carbon and nitrogen contents were the critical
      environmental factors affecting bacterial elevational distribution in Changbai
      Mountain tundra. This suggested that ecological niche-based environmental
      filtering processes related to soil carbon and nitrogen contents could play a
      dominant role in structuring bacterial communities along the elevational
      gradient. 

PMID- 26217309
TI  - Differing roles of autophagy in HIV-associated neurocognitive impairment and
      encephalitis with implications for morphine co-exposure.
AB  - We investigated the role of autophagy in HIV-infected subjects with
      neurocognitive impairment (NCI) +/- HIV encephalitis (HIVE), many of which had a
      history of polysubstance abuse/dependence, using post-mortem brain tissues to
      determine whether differences in autophagy related factors may be more associated
      with NCI or NCI-encephalitis. Using qRT-PCR, we detected significant differences
      in gene expression levels with SQSTM1, LAMP1 higher in HIV-infected subjects
      without NCI while ATG5, SQSTM1 were then lower in HIV infection/NCI and ATG7,
      SQSTM1 being higher in NCI-HIVE. Immunohistochemical labeling of these autophagy
      associated proteins (also including Beclin 1 and LC3B) in Iba1-positive
      microglial cells showed generally higher immunoreactivity in the NCI and NCI-HIVE
      groups with more focal vs. diffuse patterns of expression in the NCI-HIVE group.
      Furthermore, analysis of microarray data from these same subjects found
      significantly higher levels of LAMP1 in NCI-HIVE compared to uninfected subjects
      in the basal ganglia. Finally, we tested the effect of supernatant from HIV-1
      infected microglia and HIV-1 Tat protein in combination with morphine on neurons
      in vitro and found opposing events with both significant inhibition of autophagic
      flux and reduced dendrite length for morphine and supernatant treatment while Tat
      and morphine exposure resulted in lower autophagic activity at an earlier time
      point and higher levels in the later. These results suggest autophagy genes and
      their corresponding proteins may be differentially regulated at the
      transcriptional, translational, and post-translational levels in the brain during
      various stages of the HIV disease and that infected individuals exposed to
      morphine can experience mixed signaling of autophagic activity which could lead
      to more severe NCI than those without opioid use. 

PMID- 26217311
TI  - Simultaneous regulation of cell size and chromosome replication in bacteria.
AB  - Bacteria are able to maintain a narrow distribution of cell sizes by regulating
      the timing of cell divisions. In rich nutrient conditions, cells divide much
      faster than their chromosomes replicate. This implies that cells maintain
      multiple rounds of chromosome replication per cell division by regulating the
      timing of chromosome replications. Here, we show that both cell size and
      chromosome replication may be simultaneously regulated by the long-standing
      initiator accumulation strategy. The strategy proposes that initiators are
      produced in proportion to the volume increase and is accumulated at each origin
      of replication, and chromosome replication is initiated when a critical amount
      per origin has accumulated. We show that this model maps to the incremental model
      of size control, which was previously shown to reproduce experimentally observed
      correlations between various events in the cell cycle and explains the
      exponential dependence of cell size on the growth rate of the cell. Furthermore,
      we show that this model also leads to the efficient regulation of the timing of
      initiation and the number of origins consistent with existing experimental
      results. 

PMID- 26217312
TI  - Potential of metabolomics to reveal Burkholderia cepacia complex pathogenesis and
      antibiotic resistance.
AB  - The Burkholderia cepacia complex (Bcc) is a collection of closely related,
      genetically distinct, ecologically diverse species known to cause life
      threatening infections in cystic fibrosis (CF) patients. By virtue of a flexible
      genomic structure and diverse metabolic activity, Bcc bacteria employ a wide
      array of virulence factors for pathogenesis in CF patients and have developed
      resistance to most of the commonly used antibiotics. However, the mechanism of
      pathogenesis and antibiotic resistance is still not fully understood. This mini
      review discusses the established and potential virulence determinants of Bcc and
      some of the contemporary strategies including transcriptomics and proteomics used
      to identify these traits. We also propose the application of metabolic profiling,
      a cost-effective modern-day approach to achieve new insights. 

PMID- 26217310
TI  - Interaction of antibacterial compounds with RND efflux pumps in Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa infections are becoming increasingly difficult to treat
      due to intrinsic antibiotic resistance and the propensity of this pathogen to
      accumulate diverse resistance mechanisms. Hyperexpression of efflux pumps of the
      Resistance-Nodulation-Cell Division (RND)-type multidrug efflux pumps (e.g.,
      MexAB-OprM), chromosomally encoded by mexAB-oprM, mexCD-oprJ, mexEF-oprN, and
      mexXY (-oprA) is often detected in clinical isolates and contributes to worrying
      multi-drug resistance phenotypes. Not all antibiotics are affected to the same
      extent by the aforementioned RND efflux pumps. The impact of efflux on antibiotic
      activity varies not only between different classes of antibiotics but also
      between members of the same family of antibiotics. Subtle differences in
      physicochemical features of compound-pump and compound-solvent interactions
      largely determine how compounds are affected by efflux activity. The combination
      of different high-resolution techniques helps to gain insight into the
      functioning of these molecular machineries. This review discusses substrate
      recognition patterns based on experimental evidence and computer simulations with
      a focus on MexB, the pump subunit of the main RND transporter in P. aeruginosa. 

PMID- 26217313
TI  - Repurposing FDA-approved drugs as therapeutics to treat Rift Valley fever virus
      infection.
AB  - There are currently no FDA-approved therapeutics available to treat Rift Valley
      fever virus (RVFV) infection. In an effort to repurpose drugs for RVFV treatment,
      a library of FDA-approved drugs was screened to determine their ability to
      inhibit RVFV. Several drugs from varying compound classes, including inhibitors
      of growth factor receptors, microtubule assembly/disassembly, and DNA synthesis,
      were found to reduce RVFV replication. The hepatocellular and renal cell
      carcinoma drug, sorafenib, was the most effective inhibitor, being non-toxic and
      demonstrating inhibition of RVFV in a cell-type and virus strain independent
      manner. Mechanism of action studies indicated that sorafenib targets at least two
      stages in the virus infectious cycle, RNA synthesis and viral egress.
      Computational modeling studies also support this conclusion. siRNA knockdown of
      Raf proteins indicated that non-classical targets of sorafenib are likely
      important for the replication of RVFV. 

PMID- 26217314
TI  - Challenges and opportunities in understanding microbial communities with
      metagenome assembly (accompanied by IPython Notebook tutorial).
AB  - Metagenomic investigations hold great promise for informing the genetics,
      physiology, and ecology of environmental microorganisms. Current challenges for
      metagenomic analysis are related to our ability to connect the dots between
      sequencing reads, their population of origin, and their encoding functions.
      Assembly-based methods reduce dataset size by extending overlapping reads into
      larger contiguous sequences (contigs), providing contextual information for
      genetic sequences that does not rely on existing references. These methods,
      however, tend to be computationally intensive and are again challenged by
      sequencing errors as well as by genomic repeats While numerous tools have been
      developed based on these methodological concepts, they present confounding
      choices and training requirements to metagenomic investigators. To help with
      accessibility to assembly tools, this review also includes an IPython Notebook
      metagenomic assembly tutorial. This tutorial has instructions for execution any
      operating system using Amazon Elastic Cloud Compute and guides users through
      downloading, assembly, and mapping reads to contigs of a mock microbiome
      metagenome. Despite its challenges, metagenomic analysis has already revealed
      novel insights into many environments on Earth. As software, training, and data
      continue to emerge, metagenomic data access and its discoveries will to grow. 

PMID- 26217315
TI  - Evaluation of the matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry Bruker Biotyper for identification of Penicillium marneffei,
      Paecilomyces species, Fusarium solani, Rhizopus species, and Pseudallescheria
      boydii.
AB  - We evaluated the performance of matrix-assisted laser desorption ionization-time
      of flight mass spectrometry (MALDI-TOF MS), the MALDI Bruker Biotyper system
      (microflex LT; Bruker Daltonik GmbH, Bremen, Germany), on the identification of
      50 isolates of clinically encountered molds, including Penicillium marneffei (n =
      28), Paecilomyces species (n = 12), Fusarium solani (n = 6), Rhizopus species (n
      = 3), and Pseudallescheria boydii (n = 1). The isolates were identified to
      species levels by sequence analysis of the internal transcribed spacer (ITS)
      regions using primers ITS1 and ITS4. None of the 28 genetically well
      characterized isolates of P. marneffei were identified as P. marneffei by MALDI
      TOF MS, because P. marneffei was not present in either Bruker general library (DB
      5627) or Bruker filamentous fungi library V1.0. However, the rate of accurate
      identification as P. marneffei (score value >= 2.000) was 85.7% based on newly
      created database from one P. marneffei strain (NTUH-3370) by MALDI Biotyper
      system. Sequencing analysis of these 22 non-P. marneffei isolates of molds
      revealed seven Paecilomyces variotii, six F. solani, four Paecilomyces lilacinus,
      and one each of Paecilomyces sinensis, Rhizopus arrhizus, R. oryzae, R.
      microspores, and P. boydii. Although all the seven P. variotii isolates, four of
      the six F. solani, two of the four P. lilacinus, and two of the three isolates of
      Rhizopus species, and the P. boydii isolate had concordant identification results
      between MALDI-TOF MS and sequencing analysis, the score values of these isolates
      were all of <1.700. This study indicated that the MALDI Bruker Biotyper is
      ineffective for identifying P. marneffei and other unusual molds because of the
      current database limitations. Therefore, it is necessary to continuously update
      the MALDI-TOF MS databases. 

PMID- 26217316
TI  - The effects of silver nanoparticles on intact wastewater biofilms.
AB  - Silver nanoparticles (Ag-NPs) have strong antibacterial properties, which may
      adversely affect biological wastewater treatment processes. To determine the
      overall effect, intact biofilm samples were collected from the rotating
      biological contactor at the local wastewater treatment plant and treated with 200
      mg Ag/L Ag-NPs for 24 h. The biofilm uptake of Ag-NPs was monitored with
      transmission electron microscopy. Forty-five minutes after Ag-NP application, Ag
      NPs were seen in the biofilm extracellular polymeric substances (EPS). After 24
      h, Ag-NPs had entered certain microbial cells, while other cells contained no
      observable Ag-NPs. Some cells were dying after the uptake of Ag-NPs. However,
      there was no significant reduction in cultivable bacteria in the biofilms, based
      on heterotrophic plate counts (HPC). While this may indicate that wastewater
      biofilms are highly resistant to Ag-NPs, the HPC represents only a small portion
      of the total microbial population. To further investigate the effects of Ag-NPs,
      a GeoChip microarray was used to directly detect changes in the functional gene
      structure of the microbial community in the biofilm. A clear decrease (34.6%
      decreases in gene number) in gene diversity was evident in the GeoChip analysis.
      However, the complete loss of any specific gene was rare. Most gene families
      present in both treated and untreated biofilms. However, this doesn't necessarily
      mean that there was no change in these families. Signal intensity decreased in
      certain variants in each family while other variants increased to compensate the
      effects of Ag-NPs. The results indicate that Ag-NP treatment decreased microbial
      community diversity but did not significantly affect the microbial community
      function. This provides direct evidence for the functional redundancy of
      microbial community in engineered ecosystems such as wastewater biofilms. 

PMID- 26217317
TI  - Auto-acetylation on K289 is not essential for HopZ1a-mediated plant defense
      suppression.
AB  - The Pseudomonas syringae type III-secreted effector HopZ1a is a member of the
      HopZ/YopJ superfamily of effectors that triggers immunity in Arabidopsis. We have
      previously shown that HopZ1a suppresses both local [effector-triggered immunity
      (ETI)] and systemic immunity [systemic acquired resistance (SAR)] triggered by
      the heterologous effector AvrRpt2. HopZ1a has been shown to possess
      acetyltransferase activity, and this activity is essential to trigger immunity in
      Arabidopsis. HopZ1a acetyltransferase activity has been reported to require the
      auto-acetylation of the effector on a specific lysine (K289) residue. In this
      paper we analyze the relevance of autoacetylation of lysine residue 289 in HopZ1a
      ability to suppress plant defenses, and on the light of the results obtained, we
      also revise its relevance for HopZ1a avirulence activity. Our results indicate
      that, while the HopZ1a(K289R) mutant is impaired to some degree in its virulence
      and avirulence activities, is by no means phenotypically equivalent to the
      catalytically inactive HopZ1a(C216A), since it is still able to trigger a defense
      response that induces detectable macroscopic HR and effectively protects
      Arabidopsis from infection, reducing growth of P. syringae within the plant. We
      also present evidence that the HopZ1a(K289R) mutant still displays virulence
      activities, partially suppressing both ETI and SAR. 

PMID- 26217318
TI  - Crassostrea gigas mortality in France: the usual suspect, a herpes virus, may not
      be the killer in this polymicrobial opportunistic disease.
AB  - Successive disease outbreaks in oyster (Crassostrea gigas) beds in France have
      resulted in dramatic losses in production, and subsequent decline in the oyster
      farming industry. Deaths of juvenile oysters have been associated with the
      presence of a herpes virus (OsHV-1 MUvar) and bacterial populations of the genus
      Vibrio. Although the pathogenicity of OsHV-1 MUvar, as well as several strains of
      Vibrio has been demonstrated by experimental infections, our understanding of the
      complexity of infections occurring in the natural environment remains limited. In
      the present study, we use specific-pathogen-free (SPF) oysters infected in an
      estuarine environment to study the diversity and dynamics of cultured microbial
      populations during disease expression. We observe that rapid Vibrio colonization
      followed by viral replication precedes oyster death. No correlation was found
      between the vibrio concentration and viral load in co-infected animals. We show
      that the quantity of viral DNA is a predictor of mortality, however, in the
      absence of bacteria, a high load of herpes virus is not sufficient to induce the
      full expression of the disease. In addition, we demonstrate that juvenile
      mortalities can occur in the absence of herpes virus, indicating that the herpes
      virus appears neither essential nor sufficient to cause juvenile deaths; whereas
      bacteria are necessary for the disease. Finally, we demonstrate that oysters are
      a reservoir of putative pathogens, and that the geographic origin, age, and
      cultivation method of oysters influence disease expression. 

PMID- 26217319
TI  - Challenges and perspectives in combinatorial assembly of novel exopolysaccharide
      biosynthesis pathways.
AB  - Because of their rheological properties various microbial polysaccharides are
      applied as thickeners and viscosifiers both in food and non-food industries. A
      broad variety of microorganisms secrete structurally diverse exopolysaccharides
      (EPS) that contribute to their surface attachment, protection against abiotic or
      biotic stress factors, and nutrient gathering. Theoretically, a massive number of
      EPS structures are possible through variations in monosaccharide sequences,
      condensation linkages and non-sugar decorations. Given the already-high diversity
      of EPS structures, taken together with the principal of combinatorial
      biosynthetic pathways, microbial polysaccharides are an attractive class of
      macromolecules with which to generate novel structures via synthetic biology
      approaches. However, previous manipulations primarily focused on increasing
      polysaccharide yield, with structural modifications restricted to removal of side
      chains or non-sugar decorations. This article outlines the biosynthetic pathways
      of the bacterial heteroexopolysaccharides xanthan and succinoglycan, which are
      used as thickening and stabilizing agents in food and non-food industries.
      Challenges and perspectives of combining synthetic biology approaches with
      directed evolution to overcome obstacles in assembly of novel EPS biosynthesis
      pathways are discussed. 

PMID- 26217320
TI  - Light-driven increase in carbon yield is linked to maintenance in the
      proteorhodopsin-containing Photobacterium angustum S14.
AB  - A type of photoheterotrophic bacteria contain a transmembrane light-driven proton
      pump called proteorhodopsins (PRs). Due to the prevalence of these organisms in
      the upper water column of the World's Ocean, and their potential for light-driven
      ATP generation, they have been suggested to significantly influence energy and
      matter flows in the biosphere. To date, evidence for the significance of the
      light-driven metabolism of PR-containing prokaryotes has been obtained by
      comparing growth in batch culture, under light versus dark conditions, and it
      appears that responses to light are linked to unfavorable conditions, which so
      far have not been well parameterized. We studied light responses to carbon yields
      of the PR-containing Photobacterium angustum S14 using continuous culture
      conditions and light-dark cycles. We observed significant effects of light-dark
      cycles compared to dark controls, as well as significant differences between
      samples after 12 h illumination versus 12 h darkness. However, these effects were
      only observed under higher cell counts and lower pH associated with higher
      substrate concentrations. Under these substrate levels Pirt's maintenance
      coefficient was higher when compared to lower substrate dark controls, and
      decreased under light-dark cycles. It appears that light responses by P. angustum
      S14 are induced by the energetic status of the cells rather than by low substrate
      concentrations. 

PMID- 26217321
TI  - Impact of different water activities (a w) adjusted by solutes on high pressure
      high temperature inactivation of Bacillus amyloliquefaciens spores.
AB  - Much research has been conducted to comprehend the mechanisms of high pressure
      (HP) inactivation of spores in aqueous systems but for food model systems these
      information are scarce. In these systems spores can interact with ingredients
      which then could possibly lead to retarded or reduced inactivation, which can
      cause a problem for the sterilization process. The protective mechanism of a
      reduced a w-value is still unclear. HP processing might prove valuable to
      overcome protective effects of solutes and achieve shorter process times for
      sterilization under HP. To gain insight into the underlying mechanisms five a w
      values (0.9, 0.92, 0.94, 0.96, 1) were adjusted with two different solutes (NaCl,
      sucrose). Solutions were inoculated with spores of Bacillus amyloliquefaciens and
      treated at 105, 110, and 115 degrees C at 600 MPa. Further a thermal inactivation
      was conducted at the same temperatures for a comparison with the HP data.
      Afterward, the influence of HP high temperature treatment on the inactivation,
      the dipicolinic acid (DPA)-release and membrane constitution was assessed by
      plate count, HPLC and flow cytometry (FCM). The results show that during HP
      treatments sucrose and salt both have a protective effect, in which the influence
      of sucrose on the retarded inactivation is higher. The threshold water activities
      (a w), which is 0.94, here salt and sucrose have a significant influence on the
      inactivation. The comparison of thermal (105-115 degrees C) and HP and high
      temperature (600 MPa, 105-115 degrees C) treated samples showed that the time
      needed to achieve a 4-5 log10 inactivation is reduced from 45 (a w = 1) to 75 (a
      w = 0.9) min at 105 degrees C to 3 (a w = 1) to 15 (a w = 0.9) minutes at 600 MPa
      and 105 degrees C. The release of DPA is the rate limiting step of the
      inactivation and therefore monitoring the release is of great interest. The DPA
      release is slowed down in high concentrated solutions (e.g., sucrose, salt) in
      comparison to a w 1. Since there is a difference in the way the solutes protect
      the spore it could be seen as an inner spore membrane effect. Maybe as shown for
      vegetative microorganism the solutes can interact with membranes, e.g., the inner
      spore membrane. Flow cytometry (FCM) measurement data show a similar trend. 

PMID- 26217322
TI  - iTRAQ protein profile analysis of neuroblastoma (NA) cells infected with the
      rabies viruses rHep-Flury and Hep-dG.
AB  - The rabies virus (RABV) glycoprotein (G) is the principal contributor to the
      pathogenicity and protective immunity of RABV. In a previous work, we reported
      that recombinant rabies virus Hep-dG, which was generated by reverse genetics to
      carry two copies of the G-gene, showed lower virulence than the parental virus
      rHep-Flury in suckling mice with a better immune protection effect. To better
      understand the mechanisms underlying rabies virus attenuation and the role of
      glycoprotein G, isobaric tags for relative and absolute quantitation (iTRAQ) was
      performed to identify and quantify distinct proteins. 10 and 111 differentially
      expressed proteins were obtained in rHep-Flury and Hep-dG infection groups,
      respectively. Selected data were validated by western blot and qRT-PCR.
      Bioinformatics analysis of the distinct protein suggested that glycoprotein over
      expression in the attenuated RABV strain can induce activation of the interferon
      signaling. Furthermore, it may promote the antiviral response, MHC-I mediated
      antigen-specific T cell immune response, apoptosis and autophagy in an IFN
      dependent manner. These findings might not only improve the understanding of the
      dynamics of RABV and host interaction, but also help understand the mechanisms
      underlying innate and adaptive immunity during RABV infection. 

PMID- 26217323
TI  - Fecal microbiota transplantation and bacterial consortium transplantation have
      comparable effects on the re-establishment of mucosal barrier function in mice
      with intestinal dysbiosis.
AB  - Fecal microbiota transplantation (FMT) is a promising therapy, despite some
      reports of adverse side effects. Bacterial consortia transplantation (BCT) for
      targeted restoration of the intestinal ecosystem is considered a relatively safe
      and simple procedure. However, no systematic research has assessed the effects of
      FMT and BCT on immune responses of intestinal mucosal barrier in patients. We
      conducted complementary studies in animal models on the effects of FMT and BCT,
      and provide recommendations for improving the clinical outcomes of these
      treatments. To establish the dysbiosis model, male BALB/c mice were treated with
      ceftriaxone intra-gastrically for 7 days. After that, FMT and BCT were performed
      on ceftriaxone-treated mice for 3 consecutive days to rebuild the intestinal
      ecosystem. Post-FMT and post-BCT changes of the intestinal microbial community
      and mucosal barrier functions were investigated and compared. Disruption of
      intestinal microbial homeostasis impacted the integrity of mucosal epithelial
      layer, resulting in increased intestinal permeability. These outcomes were
      accompanied by overexpression of Muc2, significant decrease of SIgA secretion,
      and overproduction of defensins and inflammatory cytokines. After FMT and BCT,
      the intestinal microbiota recovered quickly, this was associated with better
      reconstruction of mucosal barriers and re-establishment of immune networks
      compared with spontaneous recovery (SR). Although based on a short-term study,
      our results suggest that FMT and BCT promote the re-establishment of intestinal
      microbial communities in mice with antibiotic-induced dysbiosis, and contribute
      to the temporal and spatial interactions between microbiota and mucosal barriers.
      The effects of BCT are comparable to that of FMT, especially in normalizing the
      intestinal levels of Muc2, SIgA, and defensins. 

PMID- 26217324
TI  - Genome mining and metabolic profiling of the rhizosphere bacterium Pseudomonas
      sp. SH-C52 for antimicrobial compounds.
AB  - The plant microbiome represents an enormous untapped resource for discovering
      novel genes and bioactive compounds. Previously, we isolated Pseudomonas sp. SH
      C52 from the rhizosphere of sugar beet plants grown in a soil suppressive to the
      fungal pathogen Rhizoctonia solani and showed that its antifungal activity is, in
      part, attributed to the production of the chlorinated 9-amino-acid lipopeptide
      thanamycin (Mendes et al., 2011). To get more insight into its biosynthetic
      repertoire, the genome of Pseudomonas sp. SH-C52 was sequenced and subjected to
      in silico, mutational and functional analyses. The sequencing revealed a genome
      size of 6.3 Mb and 5579 predicted ORFs. Phylogenetic analysis placed strain SH
      C52 within the Pseudomonas corrugata clade. In silico analysis for secondary
      metabolites revealed a total of six non-ribosomal peptide synthetase (NRPS) gene
      clusters, including the two previously described NRPS clusters for thanamycin and
      the 2-amino acid antibacterial lipopeptide brabantamide. Here we show that
      thanamycin also has activity against an array of other fungi and that
      brabantamide A exhibits anti-oomycete activity and affects phospholipases of the
      late blight pathogen Phytophthora infestans. Most notably, mass spectrometry led
      to the discovery of a third lipopeptide, designated thanapeptin, with a 22-amino
      acid peptide moiety. Seven structural variants of thanapeptin were found with
      varying degrees of activity against P. infestans. Of the remaining four NRPS
      clusters, one was predicted to encode for yet another and unknown lipopeptide
      with a predicted peptide moiety of 8-amino acids. Collectively, these results
      show an enormous metabolic potential for Pseudomonas sp. SH-C52, with at least
      three structurally diverse lipopeptides, each with a different antimicrobial
      activity spectrum. 

PMID- 26217325
TI  - Novel molecular markers for the detection of methanogens and phylogenetic
      analyses of methanogenic communities.
AB  - Methanogenic Archaea produce approximately one billion tons of methane annually,
      but their biology remains largely unknown. This is partially due to the large
      phylogenetic and phenotypic diversity of this group of organisms, which inhabit
      various anoxic environments including peatlands, freshwater sediments, landfills,
      anaerobic digesters and the intestinal tracts of ruminants. Research is also
      hampered by the inability to cultivate methanogenic Archaea. Therefore,
      biodiversity studies have relied on the use of 16S rRNA and mcrA [encoding the
      alpha subunit of the methyl coenzyme M (methyl-CoM) reductase] genes as molecular
      markers for the detection and phylogenetic analysis of methanogens. Here, we
      describe four novel molecular markers that should prove useful in the detailed
      analysis of methanogenic consortia, with a special focus on methylotrophic
      methanogens. We have developed and validated sets of degenerate PCR primers for
      the amplification of genes encoding key enzymes involved in methanogenesis: mcrB
      and mcrG (encoding beta and gamma subunits of the methyl-CoM reductase, involved
      in the conversion of methyl-CoM to methane), mtaB (encoding methanol-5
      hydroxybenzimidazolylcobamide Co-methyltransferase, catalyzing the conversion of
      methanol to methyl-CoM) and mtbA (encoding methylated [methylamine-specific
      corrinoid protein]:coenzyme M methyltransferase, involved in the conversion of
      mono-, di- and trimethylamine into methyl-CoM). The sensitivity of these primers
      was verified by high-throughput sequencing of PCR products amplified from DNA
      isolated from microorganisms present in anaerobic digesters. The selectivity of
      the markers was analyzed using phylogenetic methods. Our results indicate that
      the selected markers and the PCR primer sets can be used as specific tools for in
      depth diversity analyses of methanogenic consortia. 

PMID- 26217326
TI  - Cultivation-dependent and cultivation-independent characterization of hydrocarbon
      degrading bacteria in Guaymas Basin sediments.
AB  - Marine hydrocarbon-degrading bacteria perform a fundamental role in the
      biodegradation of crude oil and its petrochemical derivatives in coastal and open
      ocean environments. However, there is a paucity of knowledge on the diversity and
      function of these organisms in deep-sea sediment. Here we used stable-isotope
      probing (SIP), a valuable tool to link the phylogeny and function of targeted
      microbial groups, to investigate polycyclic aromatic hydrocarbon (PAH)-degrading
      bacteria under aerobic conditions in sediments from Guaymas Basin with uniformly
      labeled [(13)C]-phenanthrene (PHE). The dominant sequences in clone libraries
      constructed from (13)C-enriched bacterial DNA (from PHE enrichments) were
      identified to belong to the genus Cycloclasticus. We used quantitative PCR
      primers targeting the 16S rRNA gene of the SIP-identified Cycloclasticus to
      determine their abundance in sediment incubations amended with unlabeled PHE and
      showed substantial increases in gene abundance during the experiments. We also
      isolated a strain, BG-2, representing the SIP-identified Cycloclasticus sequence
      (99.9% 16S rRNA gene sequence identity), and used this strain to provide direct
      evidence of PHE degradation and mineralization. In addition, we isolated
      Halomonas, Thalassospira, and Lutibacterium sp. with demonstrable PHE-degrading
      capacity from Guaymas Basin sediment. This study demonstrates the value of
      coupling SIP with cultivation methods to identify and expand on the known
      diversity of PAH-degrading bacteria in the deep-sea. 

PMID- 26217327
TI  - Novel circular single-stranded DNA viruses identified in marine invertebrates
      reveal high sequence diversity and consistent predicted intrinsic disorder
      patterns within putative structural proteins.
AB  - Viral metagenomics has recently revealed the ubiquitous and diverse nature of
      single-stranded DNA (ssDNA) viruses that encode a conserved replication initiator
      protein (Rep) in the marine environment. Although eukaryotic circular Rep
      encoding ssDNA (CRESS-DNA) viruses were originally thought to only infect plants
      and vertebrates, recent studies have identified these viruses in a number of
      invertebrates. To further explore CRESS-DNA viruses in the marine environment,
      this study surveyed CRESS-DNA viruses in various marine invertebrate species. A
      total of 27 novel CRESS-DNA genomes, with Reps that share less than 60.1%
      identity with previously reported viruses, were recovered from 21 invertebrate
      species, mainly crustaceans. Phylogenetic analysis based on the Rep revealed a
      novel clade of CRESS-DNA viruses that included approximately one third of the
      marine invertebrate associated viruses identified here and whose members may
      represent a novel family. Investigation of putative capsid proteins (Cap) encoded
      within the eukaryotic CRESS-DNA viral genomes from this study and those in
      GenBank demonstrated conserved patterns of predicted intrinsically disordered
      regions (IDRs), which can be used to complement similarity-based searches to
      identify divergent structural proteins within novel genomes. Overall, this study
      expands our knowledge of CRESS-DNA viruses associated with invertebrates and
      explores a new tool to evaluate divergent structural proteins encoded by these
      viruses. 

PMID- 26217328
TI  - Campylobacter jejuni biofilms contain extracellular DNA and are sensitive to
      DNase I treatment.
AB  - Biofilms make an important contribution to survival and transmission of bacterial
      pathogens in the food chain. The human pathogen Campylobacter jejuni is known to
      form biofilms in vitro in food chain-relevant conditions, but the exact roles and
      composition of the extracellular matrix are still not clear. Extracellular DNA
      has been found in many bacterial biofilms and can be a major component of the
      extracellular matrix. Here we show that extracellular DNA is also an important
      component of the C. jejuni biofilm when attached to stainless steel surfaces, in
      aerobic conditions and on conditioned surfaces. Degradation of extracellular DNA
      by exogenous addition of DNase I led to rapid biofilm removal, without loss of C.
      jejuni viability. Following treatment of a surface with DNase I, C. jejuni was
      unable to re-establish a biofilm population within 48 h. Similar results were
      obtained by digesting extracellular DNA with restriction enzymes, suggesting the
      need for high molecular weight DNA. Addition of C. jejuni genomic DNA containing
      an antibiotic resistance marker resulted in transfer of the antibiotic resistance
      marker to susceptible cells in the biofilm, presumably by natural transformation.
      Taken together, this suggest that eDNA is not only an important component of C.
      jejuni biofilms and subsequent food chain survival of C. jejuni, but may also
      contribute to the spread of antimicrobial resistance in C. jejuni. The
      degradation of extracellular DNA with enzymes such as DNase I is a rapid method
      to remove C. jejuni biofilms, and is likely to potentiate the activity of
      antimicrobial treatments and thus synergistically aid disinfection treatments. 

PMID- 26217329
TI  - Temperature-dependent expression of virulence genes in fish-pathogenic bacteria.
AB  - Virulence gene expression in pathogenic bacteria is modulated by environmental
      parameters. A key factor in this expression is temperature. Its effect on
      virulence gene expression in bacteria infecting warm-blooded hosts is well
      documented. Transcription of virulence genes in these bacteria is induced upon a
      shift from low environmental to a higher host temperature (37 degrees C).
      Interestingly, host temperatures usually correspond to the optimum for growth of
      these pathogenic bacteria. On the contrary, in ectothermic hosts such as fish,
      molluscs, and amphibians, infection processes generally occur at a temperature
      lower than that for the optimal growth of the bacteria. Therefore, regulation of
      virulence gene expression in response to temperature shift has to be modulated in
      a different way to that which is found in bacteria infecting warm-blooded hosts.
      The current understanding of virulence gene expression and its regulation in
      response to temperature in fish-pathogenic bacteria is limited, but constant
      extension of our knowledge base is essential to enable a rational approach to the
      problem of the bacterial fish diseases affecting the aquaculture industry. This
      is an interesting issue and progress needs to be made in order to diminish the
      economic losses caused by these diseases. The intention of this review is, for
      the first time, to compile the scattered results existing in the field in order
      to lay the groundwork for future research. This article is an overview of those
      relevant virulence genes that are expressed at temperatures lower than that for
      optimal bacterial growth in different fish-pathogenic bacteria as well as the
      principal mechanisms that could be involved in their regulation. 

PMID- 26217330
TI  - Legacy effects of anaerobic soil disinfestation on soil bacterial community
      composition and production of pathogen-suppressing volatiles.
AB  - There is increasing evidence that microbial volatiles (VOCs) play an important
      role in natural suppression of soil-borne diseases, but little is known on the
      factors that influence production of suppressing VOCs. In the current study we
      examined whether a stress-induced change in soil microbial community composition
      would affect the production by soils of VOCs suppressing the plant-pathogenic
      oomycete Pythium. Using pyrosequencing of 16S ribosomal gene fragments we
      compared the composition of bacterial communities in sandy soils that had been
      exposed to anaerobic disinfestation (AD), a treatment used to kill harmful soil
      organisms, with the composition in untreated soils. Three months after the AD
      treatment had been finished, there was still a clear legacy effect of the former
      anaerobic stress on bacterial community composition with a strong increase in
      relative abundance of the phylum Bacteroidetes and a significant decrease of the
      phyla Acidobacteria, Planctomycetes, Nitrospirae, Chloroflexi, and Chlorobi. This
      change in bacterial community composition coincided with loss of production of
      Pythium suppressing soil volatiles (VOCs) and of suppression of Pythium impacts
      on Hyacinth root development. One year later, the composition of the bacterial
      community in the AD soils was reflecting that of the untreated soils. In
      addition, both production of Pythium-suppressing VOCs and suppression of Pythium
      in Hyacinth bioassays had returned to the levels of the untreated soil. GC/MS
      analysis identified several VOCs, among which compounds known to be antifungal,
      that were produced in the untreated soils but not in the AD soils. These
      compounds were again produced 15 months after the AD treatment. Our data indicate
      that soils exposed to a drastic stress can temporarily lose pathogen suppressive
      characteristics and that both loss and return of these suppressive
      characteristics coincides with shifts in the soil bacterial community
      composition. Our data are supporting the suggested importance of microbial VOCs
      in the natural buffer of soils against diseases caused by soil-borne pathogens. 

PMID- 26217331
TI  - Strategies of Vibrio parahaemolyticus to acquire nutritional iron during host
      colonization.
AB  - Iron is an essential element for the growth and development of virtually all
      living organisms. As iron acquisition is critical for the pathogenesis, a host
      defense strategy during infection is to sequester iron to restrict the growth of
      invading pathogens. To counteract this strategy, bacteria such as Vibrio
      parahaemolyticus have adapted to such an environment by developing mechanisms to
      obtain iron from human hosts. This review focuses on the multiple strategies
      employed by V. parahaemolyticus to obtain nutritional iron from host sources. In
      these strategies are included the use of siderophores and xenosiderophores,
      proteases and iron-protein receptor. The host sources used by V. parahaemolyticus
      are the iron-containing proteins transferrin, hemoglobin, and hemin. The
      implications of iron acquisition systems in the virulence of V. parahaemolyticus
      are also discussed. 

PMID- 26217332
TI  - Biofilm spatial organization by the emerging pathogen Campylobacter jejuni:
      comparison between NCTC 11168 and 81-176 strains under microaerobic and oxygen
      enriched conditions.
AB  - During the last years, Campylobacter has emerged as the leading cause of
      bacterial foodborne infections in developed countries. Described as an obligate
      microaerophile, Campylobacter has puzzled scientists by surviving a wide range of
      environmental oxidative stresses on foods farm to retail, and thereafter
      intestinal transit and oxidative damage from macrophages to cause human
      infection. In this study, confocal laser scanning microscopy (CLSM) was used to
      explore the biofilm development of two well-described Campylobacter jejuni
      strains (NCTC 11168 and 81-176) prior to or during cultivation under oxygen
      enriched conditions. Quantitative and qualitative appraisal indicated that C.
      jejuni formed finger-like biofilm structures with an open ultrastructure for 81
      176 and a multilayer-like structure for NCTC 11168 under microaerobic conditions
      (MAC). The presence of motile cells within the biofilm confirmed the maturation
      of the C. jejuni 81-176 biofilm. Acclimation of cells to oxygen-enriched
      conditions led to significant enhancement of biofilm formation during the early
      stages of the process. Exposure to these conditions during biofilm cultivation
      induced an even greater biofilm development for both strains, indicating that
      oxygen demand for biofilm formation is higher than for planktonic growth
      counterparts. Overexpression of cosR in the poorer biofilm-forming strain, NCTC
      11168, enhanced biofilm development dramatically by promoting an open
      ultrastructure similar to that observed for 81-176. Consequently, the regulator
      CosR is likely to be a key protein in the maturation of C. jejuni biofilm,
      although it is not linked to oxygen stimulation. These unexpected data advocate
      challenging studies by reconsidering the paradigm of fastidious requirements for
      C. jejuni growth when various subpopulations (from quiescent to motile cells)
      coexist in biofilms. These findings constitute a clear example of a survival
      strategy used by this emerging human pathogen. 

PMID- 26217333
TI  - MRJP1-containing glycoproteins isolated from honey, a novel antibacterial drug
      candidate with broad spectrum activity against multi-drug resistant clinical
      isolates.
AB  - The emergence of extended- spectrum beta-lactamase (ESBL) is the underlying cause
      of growing antibiotic resistance among Gram-negative bacteria to beta-lactam
      antibiotics. We recently reported the discovery of honey glycoproteins (glps)
      that exhibited a rapid, concentration-dependent antibacterial activity against
      both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli that
      resembled action of cell wall-active beta-lactam drugs. Glps showed sequence
      identity with the Major Royal Jelly Protein 1 (MRJP1) precursor that harbors
      three antimicrobial peptides: Jelleins 1, 2, and 4. Here, we used semi
      quantitative radial diffusion assay and broth microdilution assay to evaluate
      susceptibility of a number of multi-drug resistant (MDR) clinical isolates to the
      MRJP1-contaning honey glycoproteins. The MDR bacterial strains comprised three
      methicillin-resistant Staphylococcus aureus (MRSA), four Pseudomonas aeruginosa,
      two Klebsiella pneumoniae, two vancomycin-resistant Enterococci (VRE), and five
      ESBL identified as one Proteus mirabilis, three E. coli, and one E. coli NDM.
      Their resistance to different classes of antibiotics was confirmed using
      automated system Vitek 2. MDR isolates differed in their susceptibility to glps
      with MIC90 values ranging from 4.8 MUg/ml against B. subtilis to 14.4 MUg/ml
      against ESBL K. pneumoniae, Klebsiella spp. ESBL and E. coli and up to 33 MUg/ml
      against highly resistant strains of P. aeruginosa. Glps isolated from different
      honeys showed a similar ability to overcome bacterial resistance to beta-lactams
      suggesting that (a) their mode of action is distinct from other classes of beta
      lactams and that (b) the common glps structure was the lead structure responsible
      for the activity. The results of the current study together with our previous
      evidence of a rapid bactericidal activity of glps demonstrate that glps possess
      suitable characteristics to be considered a novel antibacterial drug candidate. 

PMID- 26217334
TI  - Antibody-Based Strategies to Prevent and Treat Influenza.
AB  - Passive immunization using antibodies is a promising alternative to other
      antiviral treatment options. The potential for seasonal protection arising from a
      single injection of antibodies is appealing and has been pursued for a number of
      infectious agents. However, until recently, antibody-based strategies to combat
      infectious agents have been hampered due to the fact that most antibodies have
      been found to be strain specific, with the virus evolving resistance in many
      cases. The discovery of broadly neutralizing antibodies (bNAbs) in influenza,
      dengue virus, and HIV, which bind to multiple, structurally diverse strains, has
      provided renewed interest in this area. This review will focus on new
      technologies that enable the discovery of bNAbs, the challenges and opportunities
      of immunotherapies as an important addition to existing antiviral therapy, and
      the role of antibody discovery in informing rational vaccine discovery - with
      agents targeting influenza specifically addressed. Multiple candidates have
      entered the clinic and raise the possibility that a single antibody or small
      combination of antibodies can effectively neutralize a wide variety of strains.
      However, challenges remain - including combating escape variants,
      pharmacodynamics of antibody distribution, and development of efficacy biomarkers
      beyond virologic endpoints. 

PMID- 26217335
TI  - MicroRNA as Type I Interferon-Regulated Transcripts and Modulators of the Innate
      Immune Response.
AB  - Type I interferons (IFNs) are an important family of cytokines that regulate
      innate and adaptive immune responses to pathogens, in cancer and inflammatory
      diseases. While the regulation and role of protein-coding genes involved in these
      responses are well characterized, the role of non-coding microRNAs in the IFN
      responses is less developed. We review the emerging picture of microRNA
      regulation of the IFN response at the transcriptional and post-transcriptional
      level. This response forms an important regulatory loop; several microRNAs target
      transcripts encoding components at many steps of the type I IFN response, both
      production and action, at the receptor, signaling, transcription factor, and
      regulated gene level. Not only do IFNs regulate positive signaling molecules but
      also negative regulators such as SOCS1. In total, 36 microRNA are reported as IFN
      regulated. Given this apparent multipronged targeting of the IFN response by
      microRNAs and their well-characterized capacity to "buffer" responses in other
      situations, the prospects of improved sequencing and microRNA targeting
      technologies will facilitate the elucidation of the broader regulatory networks
      of microRNA in this important biological context, and their therapeutic and
      diagnostic potential. 

PMID- 26217337
TI  - The Evolution of the Scavenger Receptor Cysteine-Rich Domain of the Class A
      Scavenger Receptors.
AB  - The class A scavenger receptor (cA-SR) family is a group of five evolutionarily
      related innate immune receptors. The cA-SRs are known for their promiscuous
      ligand binding; as they have been shown to bind bacteria, such as Streptococcus
      pneumoniae and Escherichia coli, as well as different modified forms of low
      density lipoprotein. Three of the five family members possess a scavenger
      receptor cysteine-rich (SRCR) domain while the remaining two receptors lack the
      domain. Previous work has suggested that the macrophage-associated receptor with
      collagenous structure (MARCO) shares a recent common ancestor with the non-SRCR
      containing receptors; however, the origin of the SRCR domain within the cA-SRs
      remains unknown. We hypothesize that the SRCR domains of the cA-SRs have a common
      origin that predates teleost fish. Using the newly available sequence data from
      sea lamprey and ghost shark genome projects, we have shown that MARCO shares a
      common ancestor with the SRCR-containing proteins. In addition, we explored the
      evolutionary relationships within the SRCR domain by reconstructing the ancestral
      SRCR domains of the cA-SRs. We identified a motif that is highly conserved
      between the cA-SR SRCR domains and the ancestral SRCR domain that consist of
      WGTVCDD. We also show that the GRAEVYY motif, a functionally important motif
      within MARCO, is poorly conserved in the other cA-SRs and in the reconstructed
      ancestral domain. Further, we identified three sites within MARCO's SRCR domain,
      which are under positive selection. Two of these sites lie adjacent to the
      conserved WGTVCDD motif, and may indicate a potential biological function for
      these sites. Together, these findings indicate a common origin of the SRCR domain
      within the cA-SRs; however, different selective pressures between the proteins
      may have caused MARCOs SRCR domain to evolve to contain different functional
      motifs when compared to the other SRCR-containing cA-SRs. 

PMID- 26217336
TI  - Cellular and Molecular Mechanisms of Chronic Kidney Disease with Diabetes
      Mellitus and Cardiovascular Diseases as Its Comorbidities.
AB  - Chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular diseases
      (CVD) are complex disorders of partly unknown genesis and mostly known
      progression factors. CVD and DM are the risk factors of CKD and are strongly
      intertwined since DM can lead to both CKD and/or CVD, and CVD can lead to kidney
      disease. In recent years, our knowledge of CKD, DM, and CVD has been expanded and
      several important experimental, clinical, and epidemiological associations have
      been reported. The tight cellular and molecular interactions between the renal,
      diabetic, and cardiovascular systems in acute or chronic disease settings are
      becoming increasingly evident. However, the (patho-) physiological basis of the
      interactions of CKD, DM, and CVD with involvement of multiple endogenous and
      environmental factors is highly complex and our knowledge is still at its
      infancy. Not only single pathways and mediators of progression of these diseases
      have to be considered in these processes but also the mutual interactions of
      these factors are essential. The recent advances in proteomics and integrative
      analysis technologies have allowed rapid progress in analyzing complex disorders
      and clearly show the opportunity for new efficient and specific therapies. More
      than a dozen pathways have been identified so far, including hyperactivity of the
      renin-angiotensin (RAS)-aldosterone system, osmotic sodium retention, endothelial
      dysfunction, dyslipidemia, RAS/RAF/extracellular-signal-regulated kinase pathway,
      modification of the purinergic system, phosphatidylinositol 3-kinase (PI 3
      kinase)-dependent signaling pathways, and inflammation, all leading to
      histomorphological alterations of the kidney and vessels of diabetic and non
      diabetic patients. Since a better understanding of the common cellular and
      molecular mechanisms of these diseases may be a key to successful identification
      of new therapeutic targets, we review in this paper the current literature about
      cellular and molecular mechanisms of CKD. 

PMID- 26217338
TI  - The Role of Mucosal Associated Invariant T Cells in Antimicrobial Immunity.
AB  - Mucosal associated invariant T (MAIT) cells are an innate-like T cell subset
      prevalent in humans and distributed throughout the blood and mucosal sites. Human
      MAIT cells are defined by the expression of the semi-invariant TCRalpha chain
      TRAV1-2/TRAJ12/20/33 and are restricted by the non-polymorphic major
      histocompatibility complex (MHC) class I-like molecule, MHC-related protein 1,
      MR1. MAIT cells are activated by small organic molecules, derived from the
      riboflavin biosynthesis pathway of bacteria and fungi, presented by MR1.
      Traditionally, MAIT cells were thought to recognize a limited number of antigens
      due to usage of an invariant TCRalpha chain and restriction by a non-polymorphic
      MHC molecule. However, recent studies demonstrate that the TCR repertoire of MAIT
      cells is more heterogeneous, suggesting there is a more diverse array of MR1
      antigens that MAIT cells can recognize. In response to infected cells, MAIT cells
      produce the pro-inflammatory cytokines, IFN-gamma and TNF, and are cytolytic.
      Studies performed in MR1-deficient mice suggest that MAIT cells can provide anti
      bacterial control within the first few days post-infection, as well as contribute
      to enhanced adaptive immunity in murine models of respiratory infections. In
      humans, the role of MAIT cells is unclear; however, evidence points to interplay
      between MAIT cells and microbial infections, including Mycobacterium
      tuberculosis. Given that MAIT cells are pro-inflammatory, serve in early control
      of bacterial infections, and appear enriched at tissue sites where microbes
      interface and gain access to the body, we postulate that they play an important
      role in antimicrobial immune responses. In this review, we discuss the most
      recent studies on the function and phenotype of MAIT cells, including their TCR
      diversity and antigenic repertoire, with a focus on the contribution of human
      MAIT cells in the immune response to microbial infection. 

PMID- 26217339
TI  - Transcription Factor T-Bet in Atlantic Salmon: Characterization and Gene
      Expression in Mucosal Tissues during Aeromonas Salmonicida Infection.
AB  - The T-box transcription factor T-bet is expressed in a number of hematopoietic
      cell types in mammals and plays an essential role in the lineage determination of
      Th1 T-helper cells and is considered as an essential feature for both innate and
      adaptive immune responses in higher vertebrates. In the present study, we have
      identified and characterized the full-length Atlantic salmon T-bet cDNA (3502
      bp). The putative primary structure of the polypeptide deduced from the cDNA
      sequence contained 612 aa, which possessed a T-box DNA binding domain.
      Phylogenetic study and gene synteny revealed it is as a homolog to mammalian T
      bet. Quantitative PCR analysis of different tissues in healthy fish showed that
      salmon T-bet gene was highly expressed in spleen, followed by head kidney, and
      was expressed in intestine, skin, and liver at lower levels. Moreover, the time
      dependent expression profile of T-bet, interferon gamma (IFNgamma), interleukin
      22 (IL-22), and natural killer enhancement factor in mucosal tissues during water
      borne infection with live Aeromonas salmonicida, indicated the involvement of T
      bet in mucosal immune response in Atlantic salmon. 

PMID- 26217341
TI  - Extracorporeal Photopheresis: Tolerogenic or Immunogenic Cell Death? Beyond
      Current Dogma.

PMID- 26217340
TI  - Preclinical Assessment of Viral Vectored and Protein Vaccines Targeting the Duffy
      Binding Protein Region II of Plasmodium Vivax.
AB  - Malaria vaccine development has largely focused on Plasmodium falciparum;
      however, a reawakening to the importance of Plasmodium vivax has spurred efforts
      to develop vaccines against this difficult to treat and at times severe form of
      relapsing malaria, which constitutes a significant proportion of human malaria
      cases worldwide. The almost complete dependence of P. vivax red blood cell
      invasion on the interaction of the P. vivax Duffy-binding protein region II
      (PvDBP_RII) with the human Duffy antigen receptor for chemokines (DARC) makes
      this antigen an attractive vaccine candidate against blood-stage P. vivax. Here,
      we generated both preclinical and clinically compatible adenoviral and poxviral
      vectored vaccine candidates expressing the Salvador I allele of PvDBP_RII -
      including human adenovirus serotype 5 (HAdV5), chimpanzee adenovirus serotype 63
      (ChAd63), and modified vaccinia virus Ankara (MVA) vectors. We report on the
      antibody and T cell immunogenicity of these vaccines in mice or rabbits, either
      used alone in a viral vectored prime-boost regime or in "mixed-modality"
      adenovirus prime - protein-in--adjuvant boost regimes (using a recombinant
      PvDBP_RII protein antigen formulated in Montanide((r))ISA720 or Abisco((r))100
      adjuvants). Antibodies induced by these regimes were found to bind to native
      parasite antigen from P. vivax infected Thai patients and were capable of
      inhibiting the binding of PvDBP_RII to its receptor DARC using an in vitro
      binding inhibition assay. In recent years, recombinant ChAd63 and MVA vectors
      have been quickly translated into human clinical trials for numerous antigens
      from P. falciparum as well as a growing number of other pathogens. The vectors
      reported here are immunogenic in small animals, elicit antibodies against
      PvDBP_RII, and have recently entered clinical trials, which will provide the
      first assessment of the safety and immunogenicity of the PvDBP_RII antigen in
      humans. 

PMID- 26217342
TI  - Editorial: "Cancer Immunotherapy: Lights and Shadows".

PMID- 26217343
TI  - Regulation of T Cell Immunity in Atopic Dermatitis by Microbes: The Yin and Yang
      of Cutaneous Inflammation.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease predominantly
      mediated by T helper cells. While numerous adaptive immune mechanisms in AD
      pathophysiology have been elucidated in detail, deciphering the impact of innate
      immunity in AD pathogenesis has made substantial progress in recent years and is
      currently a fast evolving field. As innate and adaptive immunity are intimately
      linked, cross-talks between these two branches of the immune system are
      critically influencing the resulting immune response and disease. Innate immune
      recognition of the cutaneous microbiota was identified to substantially
      contribute to immune homeostasis and shaping of protective adaptive immunity in
      the absence of inflammation. Disturbances in the composition of the skin
      microbiome with reduced microbial diversity and overabundance of Staphylococcus
      spp. have been shown to be associated with AD inflammation. Distinct
      Staphylococcus aureus associated microbial associated molecular patterns (MAMPs)
      binding to TLR2 heterodimers could be identified to initiate long-lasting
      cutaneous inflammation driven by T helper cells and consecutively local immune
      suppression by induction of myeloid-derived suppressor cells further favoring
      secondary skin infections as often seen in AD patients. Moreover dissecting
      cellular and molecular mechanisms in cutaneous innate immune sensing in AD
      pathogenesis paved the way for exploiting regulatory and anti-inflammatory
      pathways to attenuate skin inflammation. Activation of the innate immune system
      by MAMPs of non-pathogenic bacteria on AD skin alleviated cutaneous inflammation.
      The induction of tolerogenic dendritic cells, interleukin-10 expression and
      regulatory Tr1 cells were shown to mediate this beneficial effect. Thus,
      activation of innate immunity by MAMPs of non-pathogenic bacteria for induction
      of regulatory T cell phenotypes seems to be a promising strategy for treatment of
      inflammatory skin disorders such as AD. These new findings demonstrate how
      detailed analyses identify partly opposing consequences of microbe sensing by the
      innate immune system and how these mechanisms translate into AD pathogenesis as
      well as new therapeutic strategies. 

PMID- 26217345
TI  - Spatially resolved in vivo plant metabolomics by laser ablation-based mass
      spectrometry imaging (MSI) techniques: LDI-MSI and LAESI.
AB  - This short review aims to summarize the current developments and applications of
      mass spectrometry-based methods for in situ profiling and imaging of plants with
      minimal or no sample pre-treatment or manipulation. Infrared-laser ablation
      electrospray ionization and UV-laser desorption/ionization methods are reviewed.
      The underlying mechanisms of the ionization techniques-namely, laser ablation of
      biological samples and electrospray ionization-as well as variations of the LAESI
      ion source for specific targets of interest are described. 

PMID- 26217344
TI  - The quest for tolerant varieties: the importance of integrating "omics"
      techniques to phenotyping.
AB  - The primary objective of crop breeding is to improve yield and/or harvest quality
      while minimizing inputs. Global climate change and the increase in world
      population are significant challenges for agriculture and call for further
      improvements to crops and the development of new tools for research. Significant
      progress has been made in the molecular and genetic analysis of model plants.
      However, is science generating false expectations? Are 'omic techniques
      generating valuable information that can be translated into the field? The
      exploration of crop biodiversity and the correlation of cellular responses to
      stress tolerance at the plant level is currently a challenge. This viewpoint
      reviews concisely the problems one encounters when working on a crop and provides
      an outline of possible workflows when initiating cellular phenotyping via "-omic"
      techniques (transcriptomics, proteomics, metabolomics). 

PMID- 26217346
TI  - Fructan synthesis, accumulation, and polymer traits. I. Festulolium chromosome
      substitution lines.
AB  - The fructans found as storage carbohydrates in temperate forage grasses have a
      physiological role in regrowth and stress tolerance. They are also important for
      the nutritional value of fresh and preserved livestock feeds, and are potentially
      useful as feedstocks for biorefining. Seasonal variation in fructan content and
      the capacity for de novo fructan synthesis have been examined in a Festulolium
      monosomic substitution line family to investigate variation in the polymers
      produced by grasses in the ryegrass-fescue complex. There were significant
      differences between ryegrass and fescue. Fescue had low polymeric fructan content
      and a high oligomer/polymer ratio; synthesis of polymers longer than degree of
      polymerization 6 (DP6) from oligomers was slow. However, extension of polymer
      length from DP10/DP20 upward appeared to occur relatively freely, and, unlike
      ryegrass, fescue had a relatively even spread of polymer chain lengths above
      DP20. This included the presence of some very large polymers. Additionally fescue
      retained high concentrations of fructan, both polymeric and oligomeric, during
      conditions of low source/high sink demand. There were indications that major
      genes involved in the control of some of these traits might be located on fescue
      chromosome 3 opening the possibility to develop grasses optimized for specific
      applications. 

PMID- 26217347
TI  - Effect of GA-sensitivity on wheat early vigor and yield components under deep
      sowing.
AB  - Establishment of seedlings is a key factor in achievement of uniform field stands
      and, consequently, stable yields. Under Mediterranean conditions, soil moisture
      in the upper layer is limited and seedlings may be exposed to frequent
      dehydration events. The presence of the Reduced height (Rht)-B1b and Rht-D1b semi
      dominant dwarfing alleles results in insensitivity to gibberellin (GAI) and,
      hence, poor emergence from deep sowing. Introduction of alternative dwarfing
      genes and, thereby, preservation of the gibberellin response (GAR) and coleoptile
      length, contributes to better emergence from deep sowing. Initially 47 wheat
      cultivars carrying different Rht alleles were screened for their ability to
      emerge from deep sowing, and then 17 of them were selected for detailed
      physiological characterization in the field. The modern wheat lines containing
      GAI alleles showed significantly lower percentages of emergence from deep sowing
      than the GAR lines, i.e., 52 and 74%, respectively. Differences in early
      developmental stages were associated with grain yield, as indicated by a
      reduction of 37.3% in the modern GAI cultivars. Our results demonstrate the
      potential of alternative dwarfing genes for improving seedling establishment and
      grain yields in Mediterranean-like environments. 

PMID- 26217348
TI  - Characterization of culturable bacterial endophytes and their capacity to promote
      plant growth from plants grown using organic or conventional practices.
AB  - Plants have a diverse internal microbial biota that has been shown to have an
      important influence on a range of plant health attributes. Although these
      endophytes have been found to be widely occurring, few studies have correlated
      agricultural production practices with endophyte community structure and
      function. One agricultural system that focuses on preserving and enhancing soil
      microbial abundance and biodiversity is organic farming, and numerous studies
      have shown that organically managed system have increased microbial community
      characteristics. Herein, the diversity and specificity of culturable bacterial
      endophytes were evaluated in four vegetable crops: corn, tomato, melon, and
      pepper grown under organic or conventional practices. Endophytic bacteria were
      isolated from surface-sterilized shoot, root, and seed tissues and sequence
      identified. A total of 336 bacterial isolates were identified, and grouped into
      32 species and five phyla. Among these, 239 isolates were from organically grown
      plants and 97 from those grown conventionally. Although a diverse range of
      bacteria were documented, 186 were from the Phylum Firmicutes, representing 55%
      of all isolates. Using the Shannon diversity index, we observed a gradation of
      diversity in tissues, with shoots and roots having a similar value, and seeds
      having the least diversity. Importantly, endophytic microbial species abundance
      and diversity was significantly higher in the organically grown plants compared
      to those grown using conventional practices, potentially indicating that organic
      management practices may increase endophyte presence and diversity. The impact
      that these endophytes could have on plant growth and yield was evaluated by
      reintroducing them into tomato plants in a greenhouse environment. Of the
      bacterial isolates tested, 61% were found to promote tomato plant growth and 50
      64% were shown to enhance biomass accumulation, illustrating their potential
      agroecosystem application. 

PMID- 26217349
TI  - Overexpression of the transporters AtZIP1 and AtMTP1 in cassava changes zinc
      accumulation and partitioning.
AB  - Zinc deficiency in humans is a serious problem worldwide with an estimated one
      third of populations at risk for insufficient zinc in diet, which leads to
      impairment of cognitive abilities and immune system function. The goal of this
      research was to increase the bioavailable zinc in the edible portion of cassava
      roots to improve the overall zinc nutrition of populations that rely on cassava
      as a dietary staple. To increase zinc concentrations, two Arabidopsis thaliana
      genes coding for ZIP1 and MTP1 were overexpressed with a tuber-specific or
      constitutive promoter. Eighteen transgenic events from four constructs, out of a
      total of 73 events generated, showed significantly higher zinc concentrations in
      the edible portion of the storage root compared to the non-transgenic controls.
      The zinc content in the transgenic lines ranged from 4 to 73 mg/kg dry weight
      (DW) as compared to the non-transgenic control which contained 8 mg/kg. Striking
      changes in whole plant phenotype such as smaller plant size and chlorotic leaves
      were observed in transgenic lines that over accumulated zinc. In a confined field
      trial five transgenic events grown for 12 months showed a range of zinc
      concentrations from 18 to 217 mg/kg DW. Although the overexpression of zinc
      transporters was successful in increasing the zinc concentrations in 25% of the
      transgenic lines generated, it also resulted in a decrease in plant and tuber
      size and overall yield due to what appears to be zinc deficiency in the aerial
      parts of the plant. 

PMID- 26217350
TI  - Chernobyl seed project. Advances in the identification of differentially abundant
      proteins in a radio-contaminated environment.
AB  - Plants have the ability to grow and successfully reproduce in radio-contaminated
      environments, which has been highlighted by nuclear accidents at Chernobyl (1986)
      and Fukushima (2011). The main aim of this article is to summarize the advances
      of the Chernobyl seed project which has the purpose to provide proteomic
      characterization of plants grown in the Chernobyl area. We present a summary of
      comparative proteomic studies on soybean and flax seeds harvested from radio
      contaminated Chernobyl areas during two successive generations. Using
      experimental design developed for radio-contaminated areas, altered abundances of
      glycine betaine, seed storage proteins, and proteins associated with carbon
      assimilation into fatty acids were detected. Similar studies in Fukushima radio
      contaminated areas might complement these data. The results from these Chernobyl
      experiments can be viewed in a user-friendly format at a dedicated web-based
      database freely available at http://www.chernobylproteomics.sav.sk. 

PMID- 26217351
TI  - A decision support system (GesCoN) for managing fertigation in vegetable crops.
      Part II-model calibration and validation under different environmental growing
      conditions on field grown tomato.
AB  - The GesCoN model was evaluated for its capability to simulate growth, nitrogen
      uptake, and productivity of open field tomato grown under different environmental
      and cultural conditions. Five datasets collected from experimental trials carried
      out in Foggia (IT) were used for calibration and 13 datasets collected from
      trials conducted in Foggia, Perugia (IT), and Florida (USA) were used for
      validation. The goodness of fitting was performed by comparing the observed and
      simulated shoot dry weight (SDW) and N crop uptake during crop seasons, total dry
      weight (TDW), N uptake and fresh yield (TFY). In SDW model calibration, the
      relative RMSE values fell within the good 10-15% range, percent BIAS (PBIAS)
      ranged between -11.5 and 7.4%. The Nash-Sutcliffe efficiency (NSE) was very close
      to the optimal value 1. In the N uptake calibration RRMSE and PBIAS were very low
      (7%, and -1.78, respectively) and NSE close to 1. The validation of SDW (RRMSE =
      16.7%; NSE = 0.96) and N uptake (RRMSE = 16.8%; NSE = 0.96) showed the good
      accuracy of GesCoN. A model under- or overestimation of the SDW and N uptake
      occurred when higher or a lower N rates and/or a more or less efficient system
      were used compared to the calibration trial. The in-season adjustment, using the
      "SDWcheck" procedure, greatly improved model simulations both in the calibration
      and in the validation phases. The TFY prediction was quite good except in
      Florida, where a large overestimation (+16%) was linked to a different harvest
      index (0.53) compared to the cultivars used for model calibration and validation
      in Italian areas. The soil water content at the 10-30 cm depth appears to be well
      simulated by the software, and the GesCoN proved to be able to adaptively control
      potential yield and DW accumulation under limited N soil availability scenarios
      and consequently to modify fertilizer application. The DSSwell simulate SDW
      accumulation and N uptake of different tomato genotypes grown under Mediterranean
      and subtropical conditions. 

PMID- 26217352
TI  - The low molecular weight fraction of compounds released from immature wheat
      pistils supports barley pollen embryogenesis.
AB  - Pollen embryogenesis provides a useful means of generating haploid plants for
      plant breeding and basic research. Although it is well-established that the
      efficacy of the process can be enhanced by the provision of immature pistils as a
      nurse tissue, the origin and compound class of the signal molecule(s) involved is
      still elusive. Here, a micro-culture system was established to enable the
      culturing of populations of barley pollen at a density too low to allow unaided
      embryogenesis to occur, and this was then exploited to assess the effect of using
      various parts of the pistil as nurse tissue. A five-fold increase in the number
      of embryogenic calli formed was obtained by simply cutting the pistils in half.
      The effectiveness of the pistil-conditioned medium was transitory, since it
      needed replacement at least every 4 days to measurably ensure embryogenic
      development. The differential effect of various size classes of compounds present
      in the pistil-conditioned medium showed that the relevant molecule(s) was of
      molecular weight below 3 kDa. This work narrows down possible feeder molecules to
      lower molecular weight compounds and showed that the cellular origin of the
      active compound(s) is not specific to any tested part of the pistil. Furthermore,
      the increased recovery of calli during treatment with cut pistils may provide a
      useful tool for plant breeders and researchers using haploid technology in barley
      and other plant species. 

PMID- 26217353
TI  - Characterisation of betalain biosynthesis in Parakeelya flowers identifies the
      key biosynthetic gene DOD as belonging to an expanded LigB gene family that is
      conserved in betalain-producing species.
AB  - Plant betalain pigments are intriguing because they are restricted to the
      Caryophyllales and are mutually exclusive with the more common anthocyanins.
      However, betalain biosynthesis is poorly understood compared to that of
      anthocyanins. In this study, betalain production and betalain-related genes were
      characterized in Parakeelya mirabilis (Montiaceae). RT-PCR and transcriptomics
      identified three sequences related to the key biosynthetic enzyme Dopa 4,5
      dioxgenase (DOD). In addition to a LigB gene similar to that of non
      Caryophyllales species (Class I genes), two other P. mirabilis LigB genes were
      found (DOD and DOD-like, termed Class II). PmDOD and PmDOD-like had 70% amino
      acid identity. Only PmDOD was implicated in betalain synthesis based on transient
      assays of enzyme activity and correlation of transcript abundance to spatio
      temporal betalain accumulation. The role of PmDOD-like remains unknown. The
      striking pigment patterning of the flowers was due to distinct zones of red
      betacyanin and yellow betaxanthin production. The major betacyanin was the
      unglycosylated betanidin rather than the commonly found glycosides, an occurrence
      for which there are a few previous reports. The white petal zones lacked pigment
      but had DOD activity suggesting alternate regulation of the pathway in this
      tissue. DOD and DOD-like sequences were also identified in other betalain
      producing species but not in examples of anthocyanin-producing Caryophyllales or
      non-Caryophyllales species. A Class I LigB sequence from the anthocyanin
      producing Caryophyllaceae species Dianthus superbus and two DOD-like sequences
      from the Amaranthaceae species Beta vulgaris and Ptilotus spp. did not show DOD
      activity in the transient assay. The additional sequences suggests that DOD is
      part of a larger LigB gene family in betalain-producing Caryophyllales taxa, and
      the tandem genomic arrangement of two of the three B. vulgaris LigB genes
      suggests the involvement of duplication in the gene family evolution. 

PMID- 26217354
TI  - VIGS approach reveals the modulation of anthocyanin biosynthetic genes by CaMYB
      in chili pepper leaves.
AB  - The purple coloration of pepper leaves arises from the accumulation of
      anthocyanin. Three regulatory and 12 structural genes have been characterized for
      their involvement in the anthocyanin biosynthesis. Examination of the abundance
      of these genes in leaves showed that the majority of them differed between
      anthocyanin pigmented line Z1 and non-pigmented line A3. Silencing of the R2R3
      MYB transcription factor CaMYB in pepper leaves of Z1 resulted in the loss of
      anthocyanin accumulation. Moreover, the expression of multiple genes was altered
      in the silenced leaves. The expression of MYC was significantly lower in CaMYB
      silenced leaves, whereas WD40 showed the opposite pattern. Most structural genes
      including CHS, CHI, F3H, F3'5'H, DFR, ANS, UFGT, ANP, and GST were repressed in
      CaMYB-silenced foliage with the exception of PAL, C4H, and 4CL. These results
      indicated that MYB plays an important role in the regulation of anthocyanin
      biosynthetic related genes. Besides CaMYB silenced leaves rendered more
      sporulation of Phytophthora capsici Leonian indicating that CaMYB might be
      involved in the defense response to pathogens. 

PMID- 26217355
TI  - Functional redundancy of necrotrophic effectors - consequences for exploitation
      for breeding.
AB  - Necrotrophic diseases of wheat cause major losses in most wheat growing areas of
      world. Tan spot (caused by Pyrenophora tritici-repentis) and septoria nodorum
      blotch (SNB; Parastagonospora nodorum) have been shown to reduce yields by 10-20%
      across entire agri-ecological zones despite the application of fungicides and a
      heavy focus over the last 30 years on resistance breeding. Efforts by breeders to
      improve the resistance of cultivars has been compromised by the universal finding
      that resistance was quantitative and governed by multiple quantitative trait loci
      (QTL). Most QTL had a limited effect that was hard to measure precisely and
      varied significantly from site to site and season to season. The discovery of
      necrotrophic effectors has given breeding for disease resistance new methods and
      tools. In the case of tan spot in West Australia, a single effector, PtrToxA and
      its recogniser gene Tsn1, has a dominating impact in disease resistance. The
      delivery of ToxA to breeders has had a major impact on cultivar choice and
      breeding strategies. For P. nodorum, three effectors - SnToxA, SnTox1, and SnTox3
      - have been well characterized. Unlike tan spot, no one effector has a dominating
      role. Genetic analysis of various mapping populations and pathogen isolates has
      shown that different effectors have varying impact and that epistatic
      interactions also occur. As a result of these factors the deployment of these
      effectors for SNB resistance breeding is more complex. We have deleted the three
      effectors in a strain of P. nodorum and measured effector activity and disease
      potential of the triple knockout mutant. The culture filtrate causes necrosis in
      several cultivars and the strain causes disease, albeit the overall levels are
      less than in the wild type. Modeling of the field disease resistance scores of
      cultivars from their reactions to the microbially expressed effectors SnToxA,
      SnTox1, and SnTox3 is significantly improved by including the response to the
      triple knockout mutant culture filtrate. This indicates that one or more further
      effectors are secreted into the culture filtrate. We conclude that the in vitro
      secreted necrotrophic effectors explain a very large part of the disease response
      of wheat germplasm and that this method of resistance breeding promises to
      further reduce the impact of these globally significant diseases. 

PMID- 26217356
TI  - Genome-wide digital transcript analysis of putative fruitlet abscission related
      genes regulated by ethephon in litchi.
AB  - The high level of physiological fruitlet abscission in litchi (Litchi chinensis
      Sonn.) causes severe yield loss. Cell separation occurs at the fruit abscission
      zone (FAZ) and can be triggered by ethylene. However, a deep knowledge of the
      molecular events occurring in the FAZ is still unknown. Here, genome-wide digital
      transcript abundance (DTA) analysis of putative fruit abscission related genes
      regulated by ethephon in litchi were studied. More than 81 million high quality
      reads from seven ethephon treated and untreated control libraries were obtained
      by high-throughput sequencing. Through DTA profile analysis in combination with
      Gene Ontology and KEGG pathway enrichment analyses, a total of 2730 statistically
      significant candidate genes were involved in the ethephon-promoted litchi
      fruitlet abscission. Of these, there were 1867 early-responsive genes whose
      expressions were up- or down-regulated from 0 to 1 d after treatment. The most
      affected genes included those related to ethylene biosynthesis and signaling,
      auxin transport and signaling, transcription factors (TFs), protein
      ubiquitination, ROS response, calcium signal transduction, and cell wall
      modification. These genes could be clustered into four groups and 13 subgroups
      according to their similar expression patterns. qRT-PCR displayed the expression
      pattern of 41 selected candidate genes, which proved the accuracy of our DTA
      data. Ethephon treatment significantly increased fruit abscission and ethylene
      production of fruitlet. The possible molecular events to control the ethephon
      promoted litchi fruitlet abscission were prompted out. The increased ethylene
      evolution in fruitlet would suppress the synthesis and polar transport of auxin
      and trigger abscission signaling. To the best of our knowledge, it is the first
      time to monitor the gene expression profile occurring in the FAZ-enriched pedicel
      during litchi fruit abscission induced by ethephon on the genome-wide level. This
      study will contribute to a better understanding for the molecular regulatory
      mechanism of fruit abscission in litchi. 

PMID- 26217357
TI  - Role of proline and pyrroline-5-carboxylate metabolism in plant defense against
      invading pathogens.
AB  - Pyrroline-5-carboxylate (P5C) is an intermediate product of both proline
      biosynthesis and catabolism. Recent evidences indicate that proline-P5C
      metabolism is tightly regulated in plants, especially during pathogen infection
      and abiotic stress. However, role of P5C and its metabolism in plants has not yet
      been fully understood. Studies indicate that P5C synthesized in mitochondria has
      a role in both resistance (R)-gene-mediated and non-host resistance against
      invading pathogens. Proline dehydrogenase and delta-ornithine amino transferase
      encoding genes, both involved in P5C synthesis in mitochondria are implicated in
      defense response of Nicotiana benthamiana and Arabidopsis thaliana against
      bacterial pathogens. Such defense response is proposed to involve salicylic acid
      dependent pathway, reactive oxygen species (ROS) and hypersensitive response (HR)
      associated cell death. Recently HR, a form of programmed cell death (PCD), has
      been proposed to be induced by changes in mitochondrial P5C synthesis or the
      increase in P5C levels per se in plants inoculated with either a host pathogen
      carrying suitable avirulent (Avr) gene or a non-host pathogen. Consistently, A.
      thaliana mutant plants deficient in P5C catabolism showed HR like cell death when
      grown in external P5C or proline supplemented medium. Similarly, yeast and plant
      cells under oxidative stress were shown to increase ROS production and PCD due to
      increase in P5C levels. Similar mechanism has also been reported as one of the
      triggers for apoptosis in mammalian cells. This review critically analyzes
      results from various studies and enumerates the pathways for regulation of P5C
      levels in the plant cell, especially in mitochondria, during pathogen infection.
      Further, mechanisms regulating P5C- mediated defense responses, namely HR are
      outlined. This review also provides new insights into the differential role of
      proline-P5C metabolism in plants exposed to pathogen infection. 

PMID- 26217358
TI  - The role of proteomics in progressing insights into plant secondary metabolism.
AB  - The development of omics has enabled the genome-wide exploration of all kinds of
      biological processes at the molecular level. Almost every field of plant biology
      has been analyzed at the genomic, transcriptomic and proteomic level. Here we
      focus on the particular contribution that proteomic technologies have made in
      progressing knowledge and characterising plant secondary metabolism (SM) pathways
      since early expectations were created 15 years ago. We analyzed how three major
      issues in the proteomic analysis of plant SM have been implemented in various
      research studies. These issues are: (i) the selection of a suitable plant
      material rich in secondary metabolites of interest, such as specialized tissues
      and organs, and in vitro cell cultures; (ii) the proteomic strategy to access
      target proteins, either a comprehensive or a differential analysis; (iii) the
      proteomic approach, represented by the hypothesis-free discovery proteomics and
      the hypothesis-driven targeted proteomics. We also examine to what extent the
      most-advanced technologies have been incorporated into proteomic research in
      plant SM and highlight some cutting edge techniques that would strongly benefit
      the progress made in this field. 

PMID- 26217359
TI  - Function and regulation of transcription factors involved in root apical meristem
      and stem cell maintenance.
AB  - Plant roots are essential for overall plant development, growth, and performance
      by providing anchorage in the soil and uptake of nutrients and water. The primary
      root of higher plants derives from a group of pluripotent, mitotically active
      stem cells residing in the root apical meristem (RAM) which provides the basis
      for growth, development, and regeneration of the root. The stem cells in the
      Arabidopsis thaliana RAM are surrounding the quiescent center (QC), which
      consists of a group of rarely dividing cells. The QC maintains the stem cells in
      a non-cell-autonomous manner and prevents them from differentiation. The
      necessary dynamic but also tight regulation of the transition from stem cell fate
      to differentiation most likely requires complex regulatory mechanisms to
      integrate external and internal cues. Transcription factors play a central role
      in root development and are regulated by phytohormones, small signaling
      molecules, and miRNAs. In this review we give a comprehensive overview about the
      function and regulation of specific transcription factors controlling stem cell
      fate and root apical meristem maintenance and discuss the possibility of TF
      complex formation, subcellular translocations and cell-to-cell movement
      functioning as another level of regulation. 

PMID- 26217361
TI  - Molecular phenotyping of plant single cell-types enhances forward genetic
      analyses.
AB  - Recent advances in the isolation of single cell-types in plants provides an
      opportunity to conduct detailed analyses of their molecular characteristics at
      high resolution. This kind of cell-type specific molecular phenotyping is likely
      to enhance forward genetics studies to dissect the effect of mutations and
      thereby aid gene function assignment. Recent experimental results support this
      view, demonstrating that different cell-types exhibit substantial variation in
      transcript, protein, and metabolite accumulation and these molecular phenotypes
      are often sensitive to genetic and environmental alterations. The use of single
      cell-type molecular phenotyping approach to define plant gene function is most
      amenable to cell-types with well-characterized molecular tools and isolation
      protocols. 

PMID- 26217360
TI  - Verticillium longisporum infection induces organ-specific glucosinolate
      degradation in Arabidopsis thaliana.
AB  - The species Verticillium represents a group of highly destructive fungal
      pathogens, responsible for vascular wilt in a number of crops. The host response
      to infection by Verticillium longisporum at the level of secondary plant
      metabolites has not been well explored. Natural variation in the glucosinolate
      (GLS) composition of four Arabidopsis thaliana accessions was characterized: the
      accessions Bur-0 and Hi-0 accumulated alkenyl GLS, while 3-hydroxypropyl GLS
      predominated in Kn-0 and Ler-0. With respect to GLS degradation products, Hi-0
      and Kn-0 generated mainly isothiocyanates, whereas Bur-0 released epithionitriles
      and Ler-0 nitriles. An analysis of the effect on the composition of both GLS and
      its breakdown products in the leaf and root following the plants' exposure to V.
      longisporum revealed a number of organ- and accession-specific alterations. In
      the less disease susceptible accessions Bur-0 and Ler-0, colonization depressed
      the accumulation of GLS in the rosette leaves but accentuated it in the roots. In
      contrast, in the root, the level of GLS breakdown products in three of the four
      accessions fell, suggestive of their conjugation or binding to a fungal target
      molecule(s). The plant-pathogen interaction influenced both the organ- and
      accession-specific formation of GLS degradation products. 

PMID- 26217362
TI  - Evaluation of the surface free energy of plant surfaces: toward standardizing the
      procedure.
AB  - Plant surfaces have been found to have a major chemical and physical
      heterogeneity and play a key protecting role against multiple stress factors.
      During the last decade, there is a raising interest in examining plant surface
      properties for the development of biomimetic materials. Contact angle measurement
      of different liquids is a common tool for characterizing synthetic materials,
      which is just beginning to be applied to plant surfaces. However, some studies
      performed with polymers and other materials showed that for the same surface,
      different surface free energy values may be obtained depending on the number and
      nature of the test liquids analyzed, materials' properties, and surface free
      energy calculation methods employed. For 3 rough and 3 rather smooth plant
      materials, we calculated their surface free energy using 2 or 3 test liquids and
      3 different calculation methods. Regardless of the degree of surface roughness,
      the methods based on 2 test liquids often led to the under- or over-estimation of
      surface free energies as compared to the results derived from the 3-Liquids
      method. Given the major chemical and structural diversity of plant surfaces, it
      is concluded that 3 different liquids must be considered for characterizing
      materials of unknown physico-chemical properties, which may significantly differ
      in terms of polar and dispersive interactions. Since there are just few surface
      free energy data of plant surfaces with the aim of standardizing the calculation
      procedure and interpretation of the results among for instance, different
      species, organs, or phenological states, we suggest the use of 3 liquids and the
      mean surface tension values provided in this study. 

PMID- 26217363
TI  - Isolation and characterization of an osmotic stress and ABA induced histone
      deacetylase in Arachis hygogaea.
AB  - Histone acetylation, which together with histone methylation regulates gene
      activity in response to stress, is an important epigenetic modification. There is
      an increasing research focus on histone acetylation in crops, but there is no
      information to date in peanut (Arachis hypogaea). We showed that osmotic stress
      and ABA affect the acetylation of histone H3 loci in peanut seedlings by
      immunoblotting experiments. Using RNA-seq data for peanut, we found a RPD3/HDA1
      like superfamily histone deacetylase (HDAC), termed AhHDA1, whose gene is up
      regulated by PEG-induced water limitation and ABA signaling. We isolated and
      characterized AhHDA1 from A. hypogaea, showing that AhHDA1 is very similar to an
      Arabidopsis HDAC (AtHDA6) and, in recombinant form, possesses HDAC activity. To
      understand whether and how osmotic stress and ABA mediate the peanut stress
      response by epigenetics, the expression of AhHDA1 and stress-responsive genes
      following treatment with PEG, ABA, and the specific HDAC inhibitor trichostatin A
      (TSA) were analyzed. AhHDA1 transcript levels were enhanced by all three
      treatments, as was expression of peanut transcription factor genes, indicating
      that AhHDA1 might be involved in the epigenetic regulation of stress resistance
      genes that comprise the responses to osmotic stress and ABA. 

PMID- 26217365
TI  - Iron deficiency in barley plants: phytosiderophore release, iron translocation,
      and DNA methylation.
AB  - All living organisms require iron (Fe) to carry out many crucial metabolic
      pathways. Despite its high concentrations in the geosphere, Fe bio-availability
      to plant roots can be very scarce. To cope with Fe shortage, plants can activate
      different strategies. For these reasons, we investigated Fe deficient Hordeum
      vulgare L. plants by monitoring growth, phytosiderophores (PS) release, iron
      content, and translocation, and DNA methylation, with respect to Fe sufficient
      ones. Reductions of plant growth, roots to shoots Fe translocation, and increases
      in PS release were found. Experiments on DNA methylation highlighted significant
      differences between fully and hemy-methylated sequences in Fe deficient plants,
      with respect to Fe sufficient plants. Eleven DNA bands differently methylated
      were found in starved plants. Of these, five sequences showed significant
      alignment to barley genes encoding for a glucosyltransferase, a putative acyl
      carrier protein, a peroxidase, a beta-glucosidase and a transcription factor
      containing a Homeodomin. A resupply experiment was carried out on starved barley
      re-fed at 13 days after sowing (DAS), and it showed that plants did not recover
      after Fe addition. In fact, Fe absorption and root to shoot translocation
      capacities were impaired. In addition, resupplied barley showed DNA
      methylation/demethylation patterns very similar to that of barley grown in Fe
      deprivation. This last finding is very encouraging because it indicates as these
      variations/modifications could be transmitted to progenies. 

PMID- 26217364
TI  - Setting the PAS, the role of circadian PAS domain proteins during environmental
      adaptation in plants.
AB  - The per-ARNT-sim (PAS) domain represents an ancient protein module that can be
      found across all kingdoms of life. The domain functions as a sensing unit for a
      diverse array of signals, including molecular oxygen, small metabolites, and
      light. In plants, several PAS domain-containing proteins form an integral part of
      the circadian clock and regulate responses to environmental change. Moreover,
      these proteins function in pathways that control development and plant stress
      adaptation responses. Here, we discuss the role of PAS domain-containing proteins
      in anticipation, and adaptation to environmental changes in plants. 

PMID- 26217366
TI  - Comparative analysis of the phytocyanin gene family in 10 plant species: a focus
      on Zea mays.
AB  - Phytocyanins (PCs) are plant-specific blue copper proteins, which play essential
      roles in electron transport. While the origin and expansion of this gene family
      is not well-investigated in plants. Here, we investigated their evolution by
      undertaking a genome-wide identification and comparison in 10 plants:
      Arabidopsis, rice, poplar, tomato, soybean, grape, maize, Selaginella
      moellendorffii, Physcomitrella patens, and Chlamydomonas reinhardtii. We found an
      expansion process of this gene family in evolution. Except PCs in Arabidopsis and
      rice, which have described in previous researches, a structural analysis of PCs
      in other eight plants indicated that 292 PCs contained N-terminal secretion
      signals and 217 PCs were expected to have glycosylphosphatidylinositol-anchor
      signals. Moreover, 281 PCs had putative arabinogalactan glycomodules and might be
      AGPs. Chromosomal distribution and duplication patterns indicated that tandem and
      segmental duplication played dominant roles for the expansion of PC genes. In
      addition, gene organization and motif compositions are highly conserved in each
      clade. Furthermore, expression profiles of maize PC genes revealed diversity in
      various stages of development. Moreover, all nine detected maize PC genes
      (ZmUC10, ZmUC16, ZmUC19, ZmSC2, ZmUC21, ZmENODL10, ZmUC22, ZmENODL13, and
      ZmENODL15) were down-regulated under salt treatment, and five PCs (ZmUC19, ZmSC2,
      ZmENODL10, ZmUC22, and ZmENODL13) were down-regulated under drought treatment.
      ZmUC16 was strongly expressed after drought treatment. This study will provide a
      basis for future understanding the characterization of this family. 

PMID- 26217367
TI  - Transcriptional profiling of Medicago truncatula during Erysiphe pisi infection.
AB  - Resistance to powdery mildew has been studied in a number of plant species, yet
      the molecular mechanisms remain largely unknown. Transcription factors (TFs) play
      a critical role in the plant defense response by regulating the transcriptional
      machinery which coordinates the expression of a large group of genes involved in
      plant defense. Using high-throughput quantitative real-time PCR (qPCR) technology
      more than 1000 Medicago truncatula TFs were screened in a pair of susceptible and
      resistant genotypes of M. truncatula after 4 h of Erysiphe pisi infection.
      Seventy nine TF genes, belonging to 33 families showed a significant
      transcriptional change in response to E. pisi infection. Forty eight TF genes
      were differentially expressed in the resistant genotypes compared to the
      susceptible one in response to E. pisi infection, including pathogenesis-related
      transcriptional factors, AP2/EREBP (APETALA2/ETHYLENE-RESPONSIVE ELEMENT BINDING
      FACTORS), WRKY (highly conserved WRKYGQK amino-acid sequence), MYB
      (Myeloblastoma), homeodomain (HD) and zinc finger C2C2 (CYS2-CYS2), C2H2, (CYS2
      HIS2), LIM (Lin-11, Isl-1, Mec-3) gene families, which are involved in known
      defense responses. Our results suggest that these TF genes are among the E. pisi
      responsive genes in resistant M. truncatula that may constitute a regulatory
      network which controls the transcriptional changes in defense genes involved in
      resistance to E. pisi. 

PMID- 26217368
TI  - Bimodal effect of hydrogen peroxide and oxidative events in nitrite-induced rapid
      root abscission by the water fern Azolla pinnata.
AB  - In the genus Azolla rapid abscission of roots from floating fronds occurs within
      minutes in response to a variety of stresses, including exposure to nitrite. We
      found that hydrogen peroxide, though itself not an inducer of root abscission,
      modulates nitrite-induced root abscission by Azolla pinnata in a dose-dependent
      manner, with 2 mM H2O2 significantly diminishing the responsiveness to 2 mM
      NaNO2, and 10 mM H2O2 slightly enhancing it. Hypoxia, which has been found in
      other plants to result in autogenic production of H2O2, dramatically stimulated
      root abscission of A. pinnata in response to nitrite, especially for plants
      previously cultivated in medium containing 5 mM KNO3 compared to plants
      cultivated under N2-fixing conditions without combined nitrogen. Plants,
      including Azolla, produce the small signaling molecule nitric oxide (NO) from
      nitrite using nitrate reductase. We found Azolla plants to display dose-dependent
      root abscission in response to the NO donor spermine NONOate. Treatment of plants
      with the thiol-modifying agents S-methyl methanethiosulfonate or glutathione
      inhibited the nitrite-induced root abscission response. Synchrotron radiation
      based Fourier transform infrared spectromicroscopy revealed higher levels of
      carbonylation in the abscission zone of dropped roots, indicative of reaction
      products of polysaccharides with potent free radical oxidants. We hypothesize
      that metabolic products of nitrite and NO react with H2O2 in the apoplast leading
      to free-radical-mediated cleavage of structural polysaccharides and consequent
      rapid root abscission. 

PMID- 26217369
TI  - Editorial: Environmental phytoremediation: plants and microorganisms at work.

PMID- 26217370
TI  - Electron flow from PSII to PSI under high light is controlled by PGR5 but not by
      PSBS.
AB  - Absence of the Proton Gradient Regulation 5 (PGR5) protein from plant
      chloroplasts prevents the induction of strong trans-thylakoid proton gradient
      (DeltapH) and consequently also the thermal dissipation of excess energy (NPQ).
      The absence of the PSBS protein likewise prevents the formation of DeltapH
      dependent NPQ. This component of NPQ is called qE, which is nearly exclusively
      responsible for induction of NPQ upon increase in light intensity. On the other
      hand, the pgr5 mutant is not only deficient in induction of strong NPQ but it
      also lacks the capability to oxidize P700 upon increase in light intensity. This,
      in turn, results from uncontrolled electron flow toward photosystem I (PSI),
      which has been proposed to be caused by the lack of PSII down-regulation by NPQ
      and by a poor control of electron flow via the Cytochrome b6f (Cyt b6f) complex.
      Here we asked whether NPQ really is a component of such regulation of electron
      flow from PSII to PSI at high light. To this end, the two NPQ mutants pgr5 and
      npq4, the latter lacking the PSBS protein, were characterized. It is shown that
      the npq4 mutant, despite its highly reduced Plastoquinone pool, does not inhibit
      but rather enhances the oxidation of P700 in high light as compared to wild type.
      This clearly demonstrates that the control of electron flow from PSII to PSI
      cannot be assigned, even partially, to the down-regulation of PSII by NPQ but
      apparently takes place solely in Cyt b6f. Moreover, it is shown that the pgr5
      mutant can induce NPQ in very high light, but still remains deficient in P700
      oxidation. These results challenge the suggestion that NPQ, induced by PGR5
      dependent cyclic electron transfer, would have a key role in regulation of
      electron transfer from PSII to PSI. Instead, the results presented here are in
      line with our recent suggestion that both PSII and PSI function under the same
      light harvesting machinery regulated by DeltapH and the PSBS protein (Tikkanen
      and Aro, 2014; Grieco et al., 2015). 

PMID- 26217371
TI  - Continuous light increases growth, daily carbon gain, antioxidants, and alters
      carbohydrate metabolism in a cultivated and a wild tomato species.
AB  - Cultivated tomato species develop leaf injury while grown in continuous light
      (CL). Growth, photosynthesis, carbohydrate metabolism and antioxidative enzyme
      activities of a cultivated (Solanum lycopersicum L. 'Aromata') and a wild tomato
      species (Solanum pimpinellifolium L.) were compared in this study aiming to
      analyze the species-specific differences and thermoperiod effects in responses to
      CL. The species were subjected to three photoperiodic treatments for 12 days in
      climate chambers: 16-h photoperiod with a light/dark temperature of 26/16 degrees
      C (P16D10 or control); CL with a constant temperature of 23 degrees C (P24D0); CL
      with a variable temperature of 26/16 degrees C (P24D10). The results showed that
      both species grown in CL had higher dry matter production due to the continuous
      photosynthesis and a subsequent increase in carbon gain. In S. lycopersicum, the
      rate of photosynthesis and the maximum photochemical efficiency of photosystem II
      declined in CL with the development of leaf chlorosis, reduction in the leaf
      chlorophyll content and a higher activity of antioxidative enzymes. The normal
      diurnal patterns of starch and sugar were only present under control conditions.
      The results demonstrated that CL conditions mainly affected the photosynthetic
      apparatus of a cultivated species (S. lycopersicum), and to a less degree to the
      wild species (S. pimpinellifolium). The negative effects of the CL could be
      alleviated by diurnal temperature variations, but the physiological mechanisms
      behind these are less clear. The results also show that the genetic potential for
      reducing the negative effects of CL does exist in the tomato germplasm. 

PMID- 26217372
TI  - Spatial dissection of the Arabidopsis thaliana transcriptional response to downy
      mildew using Fluorescence Activated Cell Sorting.
AB  - Changes in gene expression form a crucial part of the plant response to
      infection. In the last decade, whole-leaf expression profiling has played a
      valuable role in identifying genes and processes that contribute to the
      interactions between the model plant Arabidopsis thaliana and a diverse range of
      pathogens. However, with some pathogens such as downy mildew caused by the
      biotrophic oomycete pathogen Hyaloperonospora arabidopsidis (Hpa), whole-leaf
      profiling may fail to capture the complete Arabidopsis response encompassing
      responses of non-infected as well as infected cells within the leaf. Highly
      localized expression changes that occur in infected cells may be diluted by the
      comparative abundance of non-infected cells. Furthermore, local and systemic Hpa
      responses of a differing nature may become conflated. To address this we applied
      the technique of Fluorescence Activated Cell Sorting (FACS), typically used for
      analyzing plant abiotic responses, to the study of plant-pathogen interactions.
      We isolated haustoriated (Hpa-proximal) and non-haustoriated (Hpa-distal) cells
      from infected seedling samples using FACS, and measured global gene expression.
      When compared with an uninfected control, 278 transcripts were identified as
      significantly differentially expressed, the vast majority of which were
      differentially expressed specifically in Hpa-proximal cells. By comparing our
      data to previous, whole organ studies, we discovered many highly locally
      regulated genes that can be implicated as novel in the Hpa response, and that
      were uncovered for the first time using our sensitive FACS technique. 

PMID- 26217373
TI  - Compost and biochar alter mycorrhization, tomato root exudation, and development
      of Fusarium oxysporum f. sp. lycopersici.
AB  - Soil amendments like compost and biochar are known to affect soil properties,
      plant growth as well as soil borne plant pathogens. Complex interactions based on
      microbial activity and abiotic characteristics are supposed to be responsible for
      suppressive properties of certain substrates, however, the specific mechanisms of
      action are still widely unknown. In the present study, the main focus was on the
      development of the soil borne pathogen, Fusarium oxysporum f.sp. lycopersici
      (Fol) in tomato (Solanum lycopersicum L.) and changes in root exudates of tomato
      plants grown in different soil substrate compositions, such as compost (Comp)
      alone at application rate of 20% (v/v), and in combination with wood biochar (WB;
      made from beech wood chips) or green waste biochar (GWB; made from garden waste
      residues) at application rate of 3% (v/v), and/or with additional arbuscular
      mycorrhizal fungi (AMF). The association of GWB and AMF had a positive effect on
      tomato plants growth unlike to the plants grown in WB containing a soil
      substrate. The AMF root colonization was not enhanced by the addition of WB or
      GWB in the soil substrate, though a bio-protective effect of mycorrhization was
      evident in both biochar amended treatments against Fol. Compost and biochars
      altered root exudates differently, which is evident from variable response of in
      vitro growth and development of Fol. The microconidia germination was highest in
      root exudates from plants grown in the soil containing compost and GWB, whereas
      root exudates of plants from a substrate containing WB suppressed the mycelial
      growth and development of Fol. In conclusion, the plant growth response and
      disease suppression in biochar containing substrates with additional AMF was
      affected by the feedstock type. Moreover, application of compost and biochars in
      the soil influence the quality and composition of root exudates with respect to
      their effects on soil-dwelling fungi. 

PMID- 26217374
TI  - Association mapping for kernel phytosterol content in almond.
AB  - Almond kernels are a rich source of phytosterols, which are important compounds
      for human nutrition. The genetic control of phytosterol content has not yet been
      documented in almond. Association mapping (AM), also known as linkage
      disequilibrium (LD), was applied to an almond germplasm collection in order to
      provide new insight into the genetic control of total and individual sterol
      contents in kernels. Population structure analysis grouped the accessions into
      two principal groups, the Mediterranean and the non-Mediterranean. There was a
      strong subpopulation structure with LD decaying with increasing genetic distance,
      resulting in lower levels of LD between more distant markers. A significant
      impact of population structure on LD in the almond cultivar groups was observed.
      The mean r(2) -value for all intra-chromosomal loci pairs was 0.040, whereas, the
      r(2) for the inter-chromosomal loci pairs was 0.036. For analysis of association
      between the markers and phenotypic traits five models were tested. The mixed
      linear model (MLM) approach using co-ancestry values from population structure
      and kinship estimates (K model) as covariates identified a maximum of 13
      significant associations. Most of the associations found appeared to map within
      the interval where many candidate genes involved in the sterol biosynthesis
      pathway are predicted in the peach genome. These findings provide a valuable
      foundation for quality gene identification and molecular marker assisted breeding
      in almond. 

PMID- 26217375
TI  - Measuring stress signaling responses of stomata in isolated epidermis of
      graminaceous species.
AB  - Our current understanding of guard cell signaling pathways is derived from
      studies in a small number of model species. The ability to study stomatal
      responses in isolated epidermis has been an important factor in elucidating the
      mechanisms by which the stomata of these species respond to environmental
      stresses. However, such approaches have rarely been applied to study guard cell
      signaling in the stomata of graminaceous species (including many of the world's
      major crops), in which the guard cells have a markedly different morphology to
      those in other plants. Our understanding of guard cell signaling in these
      important species is therefore much more limited. Here, we describe a procedure
      for the isolation of abaxial epidermal peels from barley, wheat and Brachypodium
      distachyon. We show that isolated epidermis from these species contains viable
      guard cells that exhibit typical responses to abscisic acid (ABA) and CO2, as
      determined by measurements of stomatal apertures. We use the epidermal peel assay
      technique to investigate in more detail interactions between different
      environmental factors in barley guard cells, and demonstrate that stomatal
      closure in response to external CO2 is inhibited at higher temperatures, whilst
      sensitivity to ABA is enhanced at 30 degrees C compared to 20 and 40 degrees C. 

PMID- 26217376
TI  - Gene duplication and the evolution of moonlighting proteins.
AB  - Gene duplication is a recurring phenomenon in genome evolution and a major
      driving force in the gain of biological functions. Here, we examine the role of
      gene duplication in the origin and maintenance of moonlighting proteins, with
      special focus on functional redundancy and innovation, molecular tradeoffs, and
      genetic robustness. An overview of specific examples-mainly from yeast-suggests a
      widespread conservation of moonlighting behavior in duplicate genes after long
      evolutionary times. Dosage amplification and incomplete subfunctionalization
      appear to be prevalent in the maintenance of multifunctionality. We discuss the
      role of gene-expression divergence and paralog responsiveness in moonlighting
      proteins with overlapping biochemical properties. Future studies analyzing
      multifunctional genes in a more systematic and comprehensive manner will not only
      enable a better understanding of how this emerging class of protein behavior
      originates and is maintained, but also provide new insights on the mechanisms of
      evolution by gene duplication. 

PMID- 26217377
TI  - Corrigendum: Simple, standardized incorporation of genetic risk into non-genetic
      risk prediction tools for complex traits: coronary heart disease as an example.
AB  - [This corrects the article on p. 254 in vol. 5, PMID: 25136350.]. 

PMID- 26217378
TI  - Best practices for evaluating single nucleotide variant calling methods for
      microbial genomics.
AB  - Innovations in sequencing technologies have allowed biologists to make incredible
      advances in understanding biological systems. As experience grows, researchers
      increasingly recognize that analyzing the wealth of data provided by these new
      sequencing platforms requires careful attention to detail for robust results.
      Thus far, much of the scientific Communit's focus for use in bacterial genomics
      has been on evaluating genome assembly algorithms and rigorously validating
      assembly program performance. Missing, however, is a focus on critical evaluation
      of variant callers for these genomes. Variant calling is essential for
      comparative genomics as it yields insights into nucleotide-level organismal
      differences. Variant calling is a multistep process with a host of potential
      error sources that may lead to incorrect variant calls. Identifying and resolving
      these incorrect calls is critical for bacterial genomics to advance. The goal of
      this review is to provide guidance on validating algorithms and pipelines used in
      variant calling for bacterial genomics. First, we will provide an overview of the
      variant calling procedures and the potential sources of error associated with the
      methods. We will then identify appropriate datasets for use in evaluating
      algorithms and describe statistical methods for evaluating algorithm performance.
      As variant calling moves from basic research to the applied setting, standardized
      methods for performance evaluation and reporting are required; it is our hope
      that this review provides the groundwork for the development of these standards. 

PMID- 26217380
TI  - The use of the comet assay for the evaluation of the genotoxicity of
      nanomaterials.

PMID- 26217379
TI  - Ancestry of the Timorese: age-related macular degeneration associated genotype
      and allele sharing among human populations from throughout the world.
AB  - We observed that the third leading cause of blindness in the world, age-related
      macular degeneration (AMD), occurs at a very low documented frequency in a
      population-based cohort from Timor-Leste. Thus, we determined a complete catalog
      of the ancestry of the Timorese by analysis of whole exome chip data and
      haplogroup analysis of SNP genotypes determined by sequencing the Hypervariable I
      and II regions of the mitochondrial genome and 17 genotyped YSTR markers obtained
      from 535 individuals. We genotyped 20 previously reported AMD-associated SNPs in
      the Timorese to examine their allele frequencies compared to and between
      previously documented AMD cohorts of varying ethnicities. For those without AMD
      (average age > 55 years), genotype and allele frequencies were similar for most
      SNPs with a few exceptions. The major risk allele of HTRA1 rs11200638 (10q26) was
      at a significantly higher frequency in the Timorese, as well as 3 of the 5
      protective CFH (1q32) SNPs (rs800292, rs2284664, and rs12066959). Additionally,
      the most commonly associated AMD-risk SNP, CFH rs1061170 (Y402H), was also seen
      at a much lower frequency in the Korean and Timorese populations than in the
      assessed Caucasian populations (C ~7 vs. ~40%, respectively). The difference in
      allele frequencies between the Timorese population and the other genotyped
      populations, along with the haplogroup analysis, also highlight the genetic
      diversity of the Timorese. Specifically, the most common ancestry groupings were
      Oceanic (Melanesian and Papuan) and Eastern Asian (specifically Han Chinese). The
      low prevalence of AMD in the Timorese population (2 of 535 randomly selected
      participants) may be due to the enrichment of protective alleles in this
      population at the 1q32 locus. 

PMID- 26217381
TI  - Efficacy and Safety of Sodium Hyaluronate with 1,4-Butanediol Diglycidyl Ether
      Compared to Sodium Carboxymethylcellulose in Preventing Adhesion Formation after
      Lumbar Discectomy.
AB  - OBJECTIVE: Epidural injection of hyaluronic acid may prevent adhesion formation
      after spine surgery, but the compounds used to stabilize hyaluronidase could
      interfere with its anti-adhesion effects. The present study was conducted as a
      clinical trial to evaluate the efficacy and safety of an experimental medical gel
      in preventing adhesion formation. METHODS: This study was designed as a
      multicenter, randomized, double-blind, and comparative controlled clinical trial
      with an observation period of 6 weeks. Subjects were randomly assigned into two
      groups: group A with sodium hyaluronate + 1,4-butanediol diglycidyl ether (BDDE)
      and group B with sodium hyaluronate + sodium carboxymethylcellulose (CMC). Visual
      analogue scale (VAS) of back and leg pain and the Oswestry disability index (ODI)
      and scar score ratings were assessed after surgery. RESULTS: Mean scar grade was
      2.37+/-1.13 in group A and 2.75+/-0.97 in group B, a statistically significant
      difference (p=0.012). VAS of back and leg pain and ODI scores decreased
      significantly from baseline to 3 and 6 weeks postoperatively in both groups
      (p<0.001). However, VAS and ODI scores were not statistically different between
      groups A and B at baseline or at 3 and 6 weeks after operation (p>0.3). The
      number of adverse reactions related to the anti-adhesion gels was not
      statistically different (p=0.569), but subsequent analysis of nervous adverse
      reactions showed group B was superior with a statistically difference (p=0.027).
      CONCLUSION: Sodium hyaluronate with BDDE demonstrated similar anti-adhesion
      properties to sodium hyaluronate with CMC. But, care should be used to nervous
      adverse reactions by using sodium hyaluronate with BDDE.

PMID- 26217382
TI  - Preliminary Experiences of the Combined Midline-Splitting French Door
      Laminoplasty with Polyether Ether Ketone (PEEK) Plate for Cervical Spondylosis
      and OPLL.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of
      cervical midline-splitting French-door laminoplasty with a polyether ether ketone
      (PEEK) plate. The authors retrospectively analyzed the results of patients with
      cervical laminoplasty miniplate (MAXPACER(r)) without bone grafts in multilevel
      cervical stenosis. METHODS: Fifteen patients (13 males and 2 females, mean age
      50.0 years (range 35-72)) with multilevel cervical stenosis (ossification of the
      posterior longitudinal ligament and cervical spondylotic myelopathy) underwent a
      combined surgery of midline-splitting French-door laminoplasty with or without
      mini plate. All 15 patients were followed for at least 12 months (mean follow-up
      13.3 months) after surgery, and a retrospective review of the clinical,
      radiological and surgical data was conducted. RESULTS: The radiographic results
      showed a significant increase over the postoperative period in anterior-posterior
      diameter (9.4+/-2.2 cm to 16.2+/-1.1 cm), open angles in cervical lamina (46.5+/
      16.0 degrees  to 77.2+/-13.1 degrees ), and sectional volume of cervical central
      canal (100.5+/-0.7 cm(2) to 146.5+/-4.9 cm(2)) (p<0.001). The sagittal alignment
      of the cervical spine was well preserved (31.7+/-10.0 degrees  to 31.2+/-7.6
      degrees , p=0.877) during the follow-up period. The clinical results were
      successful, and there were no significant intraoperative complications except for
      screw displacement in two cases. The mini plate constructs did not fail during
      the 12 month follow-up period, and the decompression was maintained. CONCLUSION:
      Despite the small cohort and short follow-up duration, the present study
      demonstrated that combined cervical expansive laminoplasty using the mini plate
      is an effective treatment for multilevel cervical stenosis.

PMID- 26217383
TI  - Bone Mineral Density Changes after Orchiectomy using a Scrotal Approach in Rats.
AB  - OBJECTIVE: To investigate a suitable animal model for studies of male
      osteoporosis. Osteoporosis has a particularly high incidence in postmenopausal
      women, resulting in a substantial amount of research with respect to this disease
      in women. However, research on osteoporosis in men is still lacking. METHODS:
      Twenty 10-week-old male Sprague Dawley rats were used in this study, including 4
      rats used to establish a baseline bone mineral density (BMD). The other 16 rats
      were divided into two groups: a sham surgery group (n=8), which underwent a sham
      operation, and an orchiectomized rat group (OCX) (n=8), which underwent bilateral
      OCX at 10 weeks of age. Bone mineral density was measured in 4 rats from both the
      sham surgery group and the OCX group 8 weeks after the surgery, while BMD in the
      remainder of the rats was measured 10 weeks post-surgery. RESULTS: Femoral BMD at
      8 weeks post-surgery was found to be significantly lower in the OCX group
      compared to the sham group; a finding that was also similar 10 weeks post
      surgery. CONCLUSION: 8 weeks after undergoing orchiectomy performed via a
      scrotal, white rats are a suitable model for studies of male osteoporosis.

PMID- 26217384
TI  - A Comparative Radiographic Analysis of Fusion Rate between L4-5 and L5-S1 in a
      Single Level Posterior Lumbar Interbody Fusion.
AB  - OBJECTIVE: This study aimed to investigate radiographic fusion rates at L4-5 and
      L5-S1 after single level posterior lumbar interbody fusion (PLIF) and evaluate
      the relationship between fusion rates and preoperative disc slope angle (DSA),
      lumbar lordosis (LL), segmental angle (SA), and pelvic parameters. METHODS: We
      conducted a retrospective review of patients who underwent single level PLIF at
      L4-5 or L5-S1 during May 2003-December 2012 at our institution. 73 patients were
      finally enrolled. Fusion was assessed by use of the Brantigan-Steffee
      classification, less than 2mm translation and less than 5 degrees  motion on the
      flexion-extension lateral radiographs. We analyzed the radiographic fusion rates,
      risk factors, and relationship of fusion rates with DSA, LL, SA, and pelvic
      parameters. RESULTS: There were 59 patients (80.8%) in the L4-5 group and 14
      (19.2%) in L5-S1 (average follow-up, 34 months). The radiographic fusion rates
      were 89.8% in the L4-5 group (53/59) and 42.9% in L5-S1 (6/14) (p<0.001).The
      preoperative DSA was significantly lesser in the L4-5 group than in the L5-S1
      group (13.1+/-8.1 degrees  vs. 27.2+/-6.7 degrees , p<0.001). The LL, SA, and
      pelvic parameters were not related with radiographic fusion rates in both groups.
      Risk factors for non-union were not identified between the two groups except for
      the surgery level (p<0.001). CONCLUSION: The radiographic fusion rate at L5-S1
      was less than half that at L4-5 after single level PLIF. This may be due to the
      anatomical and biomechanical differences between the two levels. More vigorous
      effort to achieve successful fusion at L5-S1 should be considered.

PMID- 26217385
TI  - Complications of Anterior Cervical Fusion using a Low-dose Recombinant Human Bone
      Morphogenetic Protein-2.
AB  - OBJECTIVE: There are several reports, which documented a high incidence of
      complications following the use of recombinant human bone morphogenetic protein-2
      (rhBMP-2) in anterior cervical fusions (ACFs). The objective of this study is to
      share our experience with low-dose rhBMP-2 in anterior cervical spine. METHODS:
      We performed a retrospective analysis of 197 patients who underwent anterior
      cervical fusion (ACF) with the use of recombinant human bone morphogenetic
      protein-2 (rhBMP-2) during 2007-2012. A low-dose rhBMP-2 (0.7mg/level) sponge was
      placed exclusively within the cage. In 102 patients demineralized bone matrix
      (DBM) was filled around the BMP sponge. Incidence and severity of dysphagia was
      determined by 5 points SWAL-QOL scale. RESULTS: Two patients had prolonged
      hospitalization due to BMP unrelated causes. Following the discharge, 13.2%(n=26)
      patients developed dysphagia and 8.6%(n=17) patients complained of neck swelling.
      More than half of the patients (52.9%, n=9) with neck swelling also had
      associated dysphagia; however, only 2 of these patients necessitated readmission.
      Both of these patients responded well to the intravenous dexamethasone. The use
      of DBM did not affect the incidence and severity of complications (p>0.05).
      Clinico-radiological evidence of fusion was not observed in 2 patients.
      CONCLUSION: A low-dose rhBMP-2 in ACFs is not without risk. However, the
      incidence and severity of complications seem to be lower with low-dose BMP placed
      exclusively inside the cage. Packing DBM putty around the BMP sponge does not
      affect the safety profile of rhBMP-2 in ACFs.

PMID- 26217386
TI  - Cervical Sagittal Alignment Parameters of Patients Admitted to Neurosurgery and
      Emergency Clinics in a State Hospital at Eastern Part of Turkey.
AB  - OBJECTIVE: Cervical spine encompasses a bridge role between the head and the
      lower parts of the spine and therefore has unique properties. Our aim in this
      study was to evaluate the cervical sagittal alignment parameters in pediatric and
      adult non-surgical patients and to find any differences in respect of age, sex
      and admission type. METHODS: All patients who were admitted to emergency and
      neurosurgery clinics of Diyarbakir Bismil State Hospital due to cervical spine
      problems (trauma, radiculopathy, paraspinal pain) in 2014 were enrolled
      retrospectively into the study. Cervical anterior-posterior and lateral X-rays
      were obtained. Our exclusion criteria were cervical coronal deformity,
      multitrauma, Glasgow Coma Scale <15, traumatic disruption of the cervical spine,
      history of malignancy, spinal infection, metabolic or rheumatologic diseases.
      RESULTS: There were 44 female and 55 male patients (n=99) in the study. Thirty
      five (35.35%) of the patients were younger than 18 years of age. Mean cervical
      spinal alignment parameters were as follows: -42.81+/-11.23 degrees  (OC2), 
      17.15+/-11.48 degrees  (C2-C7), -29.82+/-7.60 degrees  (T1 slope), -3.62+/-3.05
      degrees  (C3), -3.14+/-3.05 (C4), -3.80+/-2.74 degrees  (C5), -3.12+/-2.36
      degrees  (C6), -3.43+/-2.53 degrees  (C7). Positive correlations were observed
      between age-C2C7 angle, C2C7 angle-T1 slope, C3 angle-C4 angle, C4 angle-OC2
      angle, C4 angle-T1 slope, C4 angle-C5 angle. The one only negative correlation
      was between OC2 angle-C2C7 angle. CONCLUSION: In this regional study, it has been
      observed that global cervical lordosis increases as age increases. C4 vertebra is
      in the middle of this evaluation as it has many correlations with other cervical
      segments, which should be kept in mind when making surgical plans for this
      delicate spine region.

PMID- 26217387
TI  - Delayed Vertebral Artery Dissection after Posterior Cervical Fusion with
      Traumatic Cervical Instability: A Case Report.
AB  - Vascular injury presented immediately after the penetration, but delayed onset of
      vascular symptom caused by an embolism or vessel dissection after cervical fusion
      or traumatic event is extremely rare. We present a case of a 56-year-old woman
      who underwent an operation for cervical fusion for type II Odontoid process
      fracture. She presented symptoms of seizure with hemiparesis in 6 days after the
      operation. Multifocal acute infarction due to an embolism from the left VA (V3
      segment) dissection was observed without a definite screw breach the transverse
      foramen. We hereby reported the instructive case report of delayed onset of
      vertebral artery dissection after posterior cervical fusion with type II odontoid
      process fracture patient. When a cervical operation performed in the cervical
      trauma patient, even if no apparent VA injury occurs before and during the
      operation, the surgeon must take caution not to risk cerebral infarction because
      of the delayed VA dissection. 

PMID- 26217388
TI  - Grisel's Syndrome Induced by Mycobacterium tuberculosis.
AB  - Grisel's syndrome is a non-traumatic subluxation of the atlantoaxial joints,
      which is caused by an inflammatory process in the upper neck. It is rare to find
      literary reports of Grisel's syndrome with an evident pathogen in a lesion. For
      the first time in Korea, we report a 36-year-old female with Grisel's syndrome
      having an atlantoaxial subluxation, which was caused by a retropharyngeal abscess
      secondary to pulmonary Mycobacterium tuberculosis. The patient was treated with
      an anti-tuberculosis regimen and was prescribed a Philadelphia collar for the
      control of torticollis. The result of magnetic resonance imaging (MRI) showed an
      improved atlantoaxial alignment, after drug treatment and immobilization. This
      patient was neurologically intact and free from symptomatic complaints at follow
      up visit. Dynamic cervical radiograph confirmed that the atlantoaxial joints had
      been stable. The pathophysiology of Grisel's syndrome, along with anatomical
      attributes, was explained on the basis of the patient's clinical course. 

PMID- 26217389
TI  - Rapid Resolution of Traumatic Pneumatocyst in the Cervical Spine: A Case Report.
AB  - Intraosseous pneumatocyst is a benign, gas-filled, cystic lesion, and is commonly
      encountered in iliac bone or sacrum. Other locations of this lesion following
      trauma are rare, and only a handful of isolated cases have been reported. The
      pathogenesis and etiologies of this uncommon entity are various and it can
      present a diagnostic challenge. Only four previous cases have described the
      natural course of intravertebral pneumatocysts. Here, the authors report a rare
      case of traumatic pneumatocyst, which resolved rapidly without further
      complication. Possible pathogenic mechanisms are discussed and reviews of
      literatures are included. 

PMID- 26217390
TI  - Multiple Schwannomas of the Spine: Review of the Schwannomatosis or Congenital
      Neurilemmomatosis: A Case Report.
AB  - Schwannomas are the most common benign nerve sheath tumors originating in Schwann
      cells. With special conditions like neurofibromatosis type 2 or entity called
      schwannomatosis, patients develop multiple schwannomas. But in clinical setting,
      distinguishing schwannomatosis from neurofibromatosis type 2 is challengeable. We
      describe 58-year-old male who presented with severe neuropathic pain, from
      schwannomatosis featuring multiple schwannomas of spine and trunk, and underwent
      surgical treatment. We demonstrate his radiologic and clinical findings, and
      discuss about important clinical features of this condition. To confirm
      schwannomatosis, we performed brain magnetic resonance imaging, and took his
      familial history. Staged surgery was done for pathological confirmation and
      relief of the pain. Schwannomatosis and neurofibromatosis type 2 are similar but
      different disease. There are diagnostic hallmarks of these conditions, including
      familial history, pathology, and brain imaging. Because of different prognosis,
      the two diseases must be distinguished, so diagnostic tests that are mentioned
      above should be performed in caution. 

PMID- 26217391
TI  - Treatment of Polyostotic Fibrous Dysplasia of the Thoracic Spine with Intravenous
      Pamidronate: Result from 9 Months Follow Up.
AB  - Fibrous dysplasia of the spine is very rarely observed. We reported a case of a
      57-year-old woman, who presented with neck and bilateral shoulder pain with
      histologically confirmed fibrous dysplasia, involving the first and second
      thoracic vertebrae. Clinical and radiological findings were not specific for
      fibrous dysplasia. The histological biopsy was required for a confirmed
      diagnosis. Endocrine and metabolic evaluations are required to rule out diseases
      such as hyperthyroidism, Cushing syndrome and osteomalacia. Fibrous dyplasia can
      be managed by appropriate medical and surgical treatments based on the patient's
      neurological status and symptoms. Our patient was given intravenous pamidronate
      60mg/day for 3 days. After 9 months, her initial symptoms were improved, but
      computed tomography scan of the thoracic spine showed no change of the lesions. 

PMID- 26217392
TI  - Coexistence of Spinal Intramedullary Tuberculoma and Multiple Intracranial
      Tuberculomas.
AB  - Spinal intramedullary tuberculoma remains a very rare entity of central nervous
      system tuberculosis. This is the same with the coexistence of spinal
      intramedullary and intracranial tuberculomas that remains extremely rare with
      less than 20 cases reported at present. Authors describe this uncommon case by
      analyzing a 65-year-old female patient who had past history of kidney
      transplantation due to stage 5 chronic kidney disease and pulmonary tuberculosis
      on medication. The patient experiences progressive paraplegia and numbness on
      both lower extremities. Magnetic resonance imaging demonstrated an intramedullary
      mass at T9-10 level and multiple intracranial enhancing nodules. Microsurgical
      resection of spinal intramedullary mass was performed and the lesion was
      histopathologically confirmed as Mycobacterium tuberculosis. Efficient diagnosis
      and management of this rare disease are reviewed along with previously reported
      cases. 

PMID- 26217394
TI  - Intradural Extramedullary Tuberculoma of the Spinal Cord Following Tuberculous
      Meningitis.
AB  - Intradural extramedullary tuberculoma of the spinal cord (IETSC) is an uncommon
      disease which can occurs secondary to tuberculous meningitis. A 31-year-old woman
      was diagnosed as tuberculous meningitis after mental disorientation. Her
      mentality was recovered after antituberculous therapy. After 7 months of
      antituberculous therapy, paraplegia has developed. Magnetic resonance imaging
      (MRI) revealed a mass lesion between the T1 and T12 spinal levels with arachnoid
      thickening which results in the development of tuberculoma. She received surgical
      resection of IETSC followed by antituberculous therapy and neurological function
      has been improved. The two years after surgical treatment, spinal MRI showed
      syringomyelia between T1 to L1. But, her neurological outcome was not aggravated.

PMID- 26217393
TI  - Lumbosacral Plexopathy Caused by Presacral Recurrence of Colon Cancer Mimicking
      Degenerative Spinal Disease: A Case Report.
AB  - Radiculopathy triggered by degenerative spinal disease is the most common cause
      of spinal surgery, and the number of affected elderly patients is increasing.
      Radiating pain that is extraspinal in origin may distract from the surgical
      decision on how to treat a neurological presentation in the lower extremities. A
      54-year-old man with sciatica visited our outpatient clinic. He had undergone
      laminectomy and discectomy to treat spinal stenosis at another hospital, but his
      pain remained. Finally, he was diagnosed with a plexopathy caused by late
      recurrence of colorectal cancer, which compressed the lumbar plexus in the
      presacral area. This case report illustrates the potential for misdiagnosis of
      extraspinal plexopathy and the value of obtaining an accurate history. Although
      the symptoms are similar, spinal surgeons should consider both spinal and
      extraspinal origins of sciatica. 

PMID- 26217395
TI  - Allometric equations for estimating belowground biomass of Androstachys johnsonii
      Prain.
AB  - BACKGROUND: The belowground component of the trees is still poorly known because
      it needs labour- and time-intensive in situ measurements. However, belowground
      biomass (BGB) constitutes a significant share of the total forest biomass. I
      analysed the BGB allocation patterns, fitted models for estimating root
      components and root system biomasses, and called attention for its possible use
      in predicting anchoring functions of the different root components. RESULTS: More
      than half and almost one third of BGB is allocated to the lateral roots and to
      the root collar, respectively. More than 80% of the BGB is found at a depth range
      of 9.6-61.2 cm. As the tree size increased, the proportion of BGB allocated to
      taproots decreased and that allocated to lateral roots increased. All independent
      models performed almost equally, with the predictors explaining, on average, 98%
      of the variation in the BGB. CONCLUSIONS: It was hypothesised that BGB allocation
      patterns are a response of the anchoring functions of the tap and lateral roots
      and therefore, root component biomass models can be used as a methodology to
      predict anchoring functions of the different root components. Based on the fact
      that all models performed almost equally, the models using either diameter at
      breast height (DBH) exclusively as a predictor should be preferred, as tree
      height is difficult to measure. Models using the root collar diameter (RCD) only
      should be preferred when the tree is found cut down, as sometimes the RCD is
      affected by root buttress. Given the large sample size, the validation results,
      and the coverage of a wide geographical, soil and climatic range, the models
      fitted can be applied in all A. johnsonii stands in Mozambique.

PMID- 26217396
TI  - HCV infection-associated hepatocellular carcinoma in humanized mice.
AB  - BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is a major risk factor for
      chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Our aim is to
      explore molecular changes that underlie HCV infection-associated HCC in a
      humanized mouse model, in order to identify markers of HCC progression. METHODS:
      Liver proteins from human hepatocyte-engrafted and HCV-infected MUP-uPA/SCID/Bg
      mice were compared with either uninfected controls or HCV-infected but HCC
      negative mice by Western blotting. MicroRNA markers of HCC positive or uninfected
      mouse liver were analyzed by RT-PCR. RESULTS: We describe the depletion of tumor
      suppressor proteins and induction of oncoproteins and oncogenic microRNAs
      (oncomiRs) in HCV-infection associated HCC. Similar depletion of PTEN protein in
      both HCC-positive and HCV-infected but HCC-negative liver suggests that PTEN
      depletion is an early, precancerous marker of HCC. By contrast, induction of
      oncoprotein cMyc, oncomiRs (miR21, miR221 and miR141) and inflammatory response
      proteins correspond to HCC progression. CONCLUSIONS: While the loss of PTEN is
      important for the initiation of HCV infection-associated HCC, PTEN depletion by
      itself is insufficient for tumor progression. Liver tumor progression requires
      induction of oncoproteins and oncomiRs. Overall, human hepatocyte-engrafted (MUP
      uPA/SCID/Bg) mice provide a suitable small animal model for studying the effects
      of oncogenic changes that promote HCV infection associated HCC.

PMID- 26217397
TI  - Cpipe: a shared variant detection pipeline designed for diagnostic settings.
AB  - The benefits of implementing high throughput sequencing in the clinic are quickly
      becoming apparent. However, few freely available bioinformatics pipelines have
      been built from the ground up with clinical genomics in mind. Here we present
      Cpipe, a pipeline designed specifically for clinical genetic disease diagnostics.
      Cpipe was developed by the Melbourne Genomics Health Alliance, an Australian
      initiative to promote common approaches to genomics across healthcare
      institutions. As such, Cpipe has been designed to provide fast, effective and
      reproducible analysis, while also being highly flexible and customisable to meet
      the individual needs of diverse clinical settings. Cpipe is being shared with the
      clinical sequencing community as an open source project and is available at
      http://cpipeline.org. 

PMID- 26217398
TI  - Vitamin D assessment in primary care: changing patterns of testing.
AB  - BACKGROUND: Over recent years there has been increased interest in the disease
      burden associated with vitamin D deficiency. This, combined with recognition that
      the prevalence of vitamin D deficiency is high in the UK, has led to increased
      requests for vitamin D assessment from primary care clinicians. SETTING: A
      primary care cohort in Liverpool. QUESTION: How has the usefulness of vitamin D
      testing changed over time in identifying deficiency? METHODS: Vitamin D results
      from primary care practices in Liverpool were collected between 2007 and 2012,
      inclusive. Results were allocated to six cohorts based on year of request and
      each was grouped into three categories (adequate, insufficient and deficient).
      RESULTS: Vitamin D results of 9460 (74%) first tests and 3263 (26%) retests were
      analysed. Total number of requests increased 11-fold, from 503 in 2007 to 5552 in
      2012. Overall 42% of first-test results were deficient (< 30 nmol). With each
      incremental year, more cases of vitamin D deficiency were detected - but the odds
      of detecting vitamin D deficiency decreased. CONCLUSIONS: An exponential increase
      in the number of vitamin D requests was observed over this six-year period.
      Although more patients with vitamin deficiency were identified, the increased
      number of tests represents a significant cost to health services. Moreover, the
      practice of retesting too soon after treatment can be inappropriate. There is a
      need to develop clear guidance for assessing vitamin D status in primary care.

PMID- 26217399
TI  - Can we learn from the Mid-Staffordshire Inquiry or is it always someone else's
      problem?
AB  - KEY MESSAGES: Every healthcare practitioner has a responsibility to put the well
      being of patients first.Every healthcare practitioner has a responsibility in the
      maintenance of healthcare quality and each must take appropriate actions when
      alerted to poor standards.You cannot assume others will follow up patient
      concerns and take appropriate actions - the 'buck' stops with every practitioner
      on a professional register. WHY THIS MATTERS TO ME: The regrettable events at
      Stafford Hospital were avoidable and reading the inquiry report highlighted the
      extent to which the NHS, and those within it, neglected their duties of care. I
      was particularly ashamed of my Registered Nurse colleagues who appear to have
      forgotten that registration as a nurse requires attitudes and behaviours
      commensurate with the public trust that is attributed to their role. The shocking
      truth that emerges from the Francis Report(1) is that no organisation or
      profession emerges with any credit whatsoever - the Deanery, universities,
      general practitioners (GPs), the General Medical Council (GMC), the Nursing and
      Midwifery Council (NMC), Monitor.... It is clear that any number of healthcare
      professionals could have challenged what was happening and alerted the relevant
      regulatory and supervisory organisations. Those organisations could have then
      discharged their 'duties' rather than taking a benevolent and optimistic view of
      the emerging evidence and leaving it to others to act.

PMID- 26217400
TI  - The choking woman.
AB  - BACKGROUND: There is a small, but significant cohort of patients that receives
      inappropriate care, in the wrong setting, and that utilises a disproportionate
      amount of healthcare resources. People with multiple co-morbidities and often
      undetected mental illness fare better with integrated care and case management
      approaches. SETTING: In North West London, we have been working in the
      'Integrated Care Programme' for four years to try to improve the care this cohort
      receives. QUESTION: Can psychiatric intervention with case management improve
      outcomes for this cohort? METHODS: We describe the case of a 64-year-old woman
      who presented at an Emergency Department (ED) with functional dysphagia 25 times
      in the space of eight weeks. During that time, she was referred to numerous
      specialists, and had multiple invasive investigations even though her symptoms
      were not suggestive of organic pathology, and were in fact suggestive of anxiety.
      RESULTS: Her pre- and peri-psychiatric intervention healthcare costs were, on
      average, L3330/month. These reduced to an average of L276/month after three
      months of psychiatric intervention. CONCLUSIONS/DISCUSSION: We reflect on the
      possible reasons why the story unfolded in the way it did and suggest generalised
      implications for clinicians caring for this cohort and for service delivery in
      future.

PMID- 26217401
TI  - An assessment of the cost-effectiveness, safety of referral and patient
      satisfaction of a general practice teledermatology service.
AB  - BACKGROUND: In the cost-constrained NHS and in the quest for rapid diagnosis,
      teledermatology is a tool that can be used within general practice to aid in the
      diagnosis of benign-looking skin lesions and reduce referrals to secondary care.
      The setting for the study was a single general practice of 6500 patients in
      suburban Greater London. The aim of the study was to determine: (1) whether
      teledermatology in a single general practice is cost-effective, (2) whether the
      correct types of cases are being referred, and (3) if patients are satisfied with
      the service. METHODS: Teledermatology was provided by a private provider. A
      trained member of staff took photographs in the practice. A consultant
      dermatologist carried out reporting. This is a retrospective analysis of case
      records over three years. The cases were adult patients (aged 18+) using
      teledermatology for the diagnosis and management of skin lesions thought to be
      benign by the general practitioner. Cost-effectiveness was calculated by
      considering savings made through reduced referral to secondary care, taking into
      account the cost of the service. To evaluate whether the correct cases were
      referred we reviewed whether the assessing dermatologist identified any
      previously undiagnosed skin cancer. Patient satisfaction assessment was performed
      using a standard questionnaire. RESULTS: Two hundred and forty-eight patients had
      teledermatology. These were patients who would have been referred to secondary
      care for a routine appointment. Of these, 102 were subsequently referred to
      secondary care and 146 were managed within the practice. Teledermatology saved
      L12 460 over the 3-year period. Patients were followed for up to 51 months and no
      lesions were found to be malignant. Ninety-seven percent of patients rated
      themselves as satisfied/very satisfied and 93% found the procedure
      comfortable/very comfortable. The median wait for the photos to be taken was 7
      days, and 1-2 weeks for results. CONCLUSIONS: Teledermatology has been shown to
      be cost-effective, with referrals identified correctly when employed in this
      general practice setting. Satisfaction with the service was high.

PMID- 26217402
TI  - Songs of Courage.

PMID- 26217403
TI  - Figures stripped to bones, just signs and symbols - solitude, discomfort,
      incommunicability.

PMID- 26217404
TI  - Integrated care in the UK: variations on a theme?
AB  - This short review compares the experiences of Scotland and Wales in developing
      integrated care with those of England, and to some extent Northern Ireland. It is
      a companion piece to two other articles published in this issue from Scotland and
      Wales. 

PMID- 26217405
TI  - Integrated care: a Scottish perspective.
AB  - The Public Bodies (Joint Working) (Scotland) Act 2014 puts in place the framework
      for the Integration of health and social care in Scotland. Newly formed health
      and social care partnerships (HSCP), which will serve as the joint responsibility
      of NHS boards and local authorities, will work in partnership with the third
      sector, users, carers and other key stakeholders, including the independent
      sector. This paper details the underpinning features of the legislation which
      aims to put 'personal' outcomes at the centre, in order for everyone to be able
      to live longer and healthier lives at home or in a homely setting. Much activity
      is being undertaken in what is one of the single biggest changes to care services
      in Scotland. 

PMID- 26217406
TI  - Integrated care in Wales: a summary position.

PMID- 26217407
TI  - Infertility in a young woman with Type 2 diabetes.
AB  - KEY MESSAGES: Ovulatory dysfunction is the most common female cause of
      infertility in the UK.Polycystic ovarian syndrome is associated with oligo
      ovulation and Type 2 diabetes.Good glycaemic control is essential before getting
      pregnant to prevent congenital malformations and miscarriages in young women with
      Type 2 diabetes.Metformin is safe in the first trimester and reduces the rate of
      miscarriages and gestational diabetes.Labetalol, methyldopa and hydralazine are
      deemed safer in pregnancy.Women should not conceive on statins due their
      potential teratogenic effects. WHY THIS MATTERS TO ME: Polycystic ovarian
      syndrome (PCOS) is a frequently encountered condition in general practice and can
      have a significant impact on the quality of life of young women. Apart from
      addressing ovulatory problems in these women, it is important to remember to
      screen for other associated conditions such as Type 2 diabetes, hypertension or
      hypercholesterolaemia. This article outlines the pathophysiology of PCOS and its
      diagnostic pathways and also summarises the safety of medical management for the
      metabolic complications in pregnant women. It is important for healthcare
      professionals to be aware of the latest guidance for treatment of PCOS in order
      to provide high-standard evidencebased care.

PMID- 26217408
TI  - Metamorphosis.

PMID- 26217409
TI  - There was... a goat! Impressions of learning from a young visitor to a recent
      Marc Chagall exhibition in Milan.

PMID- 26217410
TI  - What to Do When Your Paper Is Rejected.

PMID- 26217411
TI  - Two Cheers for Milestones.

PMID- 26217412
TI  - Knowledge and Training of Intrauterine Devices Among Primary Care Residents:
      Implications for Graduate Medical Education.

PMID- 26217413
TI  - Negotiation Skills for Medical Educators.

PMID- 26217414
TI  - When Faced With Facebook: What Role Should Social Media Play in Selecting
      Residents?

PMID- 26217415
TI  - Prioritizing Paperwork Over Patient Care: Why Can't We Do Both?

PMID- 26217416
TI  - Bringing Specialties Together: The Power of Intra-Professional Teams.

PMID- 26217417
TI  - Applicants' Self-Reported Priorities in Selecting a Residency Program.
AB  - BACKGROUND: Residency recruitment is a high-stakes activity for all participants,
      yet there is limited information about how applicants choose among programs.
      OBJECTIVE: This study evaluated the importance applicants place on various
      residency program attributes; whether applicant priorities vary by sex,
      race/ethnicity, or specialty choice; and whether the importance of these factors
      changes over time. METHODS: Highly ranked applicants to residency programs at 2
      academic medical centers were surveyed annually from 2004 to 2012 regarding the
      importance of 26 characteristics in selecting a program. Mean ratings of
      importance for each factor were analyzed to assess priority for the overall
      applicant group, and whether priorities differed for subgroups (by sex,
      race/ethnicity, and specialty). RESULTS: Of 9669 applicants surveyed, 6285 (65%)
      responded. The 5 factors with highest rating of importance (overall and across
      all subgroups) were the program's ability to prepare residents for future
      training or position, resident esprit de corps, faculty availability and
      involvement in teaching, depth and breadth of faculty, and variety of patients
      and clinical resources. Small but significant differences in the ratings of some
      factors by sex and/or specialty group were identified. Institution-level
      characteristics, such as call rooms, salary, and benefits, were relatively
      unimportant. Applicant priorities were stable over the 9-year study period.
      CONCLUSIONS: Highly ranked applicants to competitive residency programs value
      educational aspects of the program most highly, along with resident morale. Top
      factors were consistent across subgroups and over the 9 years of the study. These
      findings have implications for resident recruitment strategies.

PMID- 26217418
TI  - Diagnostic Reasoning for ST-Segment Elevation Myocardial Infarction (STEMI)
      Interpretation Is Preserved Despite Fatigue.
AB  - BACKGROUND: Fatigue and sleepiness contribute to medical errors, although the
      effect of circadian disruption and fatigue on diagnostic reasoning skills is
      largely unknown. OBJECTIVE: To determine whether circadian disruption and fatigue
      negatively affect the emergency medicine (EM) resident's ability to make
      important clinical decisions based on electrocardiogram (ECG) interpretation.
      METHODS: Senior EM residents at 2 programs completed a questionnaire consisting
      of various measures of fatigue followed by an ECG test packet of ST-segment
      elevation myocardial infarction (STEMI) and STEMI mimics. Participants were asked
      to examine each ECG and determine whether cardiac catheterization laboratory
      activation (CLA) was indicated, and to report their confidence in their decision
      making on an 11-point, numeric rating scale. The primary outcome measured was a
      pairwise difference in accuracy of CLA between daytime and overnight testing.
      RESULTS: A total of 23 residents were enrolled in 2011 and 2012. Subjects
      demonstrated significant differences in multiple measures of sleepiness and
      fatigue during overnight periods. The median (interquartile range [IQR]) accuracy
      of CLA was not significantly different between daytime and overnight (70% [IQR,
      50-80] versus 70% [IQR, 60-70], P  =  .82). There were no significant differences
      in the median number of overcalls (CLA when not a STEMI) and undercalls (no CLA
      when a STEMI was present; P  =  .57 and .37, respectively). Diagnostic confidence
      and confidence in CLA were not statistically different between daytime and
      overnight. CONCLUSIONS: Despite a measurable degree of fatigue, senior EM
      residents experienced no decrease in their ability to accurately make CLA
      decisions based on ECG interpretation.

PMID- 26217419
TI  - Objective Structured Assessment of Technical Skills to Teach and Study Retention
      of Fourth-Degree Laceration Repair Skills.
AB  - BACKGROUND: Fourth-degree perineal lacerations are a serious but infrequent
      complication of childbirth. OBJECTIVE: We studied the long-term effect of an
      educational workshop on the knowledge and ability of obstetrics and gynecology
      residents to repair fourth-degree lacerations. METHODS: We assessed obstetrics
      and gynecology residents' baseline knowledge and skill of fourth-degree
      laceration repair by using a written examination and the Objective Structured
      Assessment of Technical Skills (OSATS). After the educational intervention (a
      lecture, a demonstrational video, and practice on a model), residents completed a
      written and OSATS posttest. Six months later, residents took the same posttests
      to determine their level of retention. Another group of residents who had not
      attended the workshop also took the tests at the 6-month mark and served as a
      control group. RESULTS: A total of 17 residents were in the intervention group
      and 11 residents in the control group. The pretest written examination mean was
      6.1/10 and the OSATS mean was 10.9/18. After the workshop, the written mean
      increased to 9.1/10 and the OSATS to 16.6/18. This improvement was statistically
      significant (P < .01). Compared to the pretest, the 6-month follow-up scores had
      a statistically significant increase (written mean, 8.0/10, P < .01, and OSATS
      mean 15.5/18, P < .01). CONCLUSIONS: Residents improved on the written
      examination and OSATS after the educational workshop and maintained this
      improvement for 6 months. This intervention may prepare graduating residents for
      repairing future fourth-degree lacerations they may not have encountered during
      training.

PMID- 26217420
TI  - Clinic Design and Continuity in Internal Medicine Resident Clinics: Findings of
      the Educational Innovations Project Ambulatory Collaborative.
AB  - BACKGROUND: Many internal medicine (IM) programs have reorganized their resident
      continuity clinics to improve trainees' ambulatory experience. Downstream effects
      on continuity of care and other clinical and educational metrics are unclear.
      METHODS: This multi-institutional, cross-sectional study included 713 IM
      residents from 12 programs. Continuity was measured using the usual provider of
      care method (UPC) and the continuity for physician method (PHY). Three clinic
      models (traditional, block, and combination) were compared using analysis of
      covariance. Multivariable linear regression analysis was used to analyze the
      effect of practice metrics and clinic model on continuity. RESULTS: UPC,
      reflecting continuity from the patient perspective, was significantly different,
      and was highest in the block model, midrange in combination model, and lowest in
      the traditional model programs. PHY, reflecting continuity from the perspective
      of the resident provider, was significantly lower in the block model than in
      combination and traditional programs. Panel size, ambulatory workload,
      utilization, number of clinics attended in the study period, and clinic model
      together accounted for 62% of the variation found in UPC and 26% of the variation
      found in PHY. CONCLUSIONS: Clinic model appeared to have a significant effect on
      continuity measured from both the patient and resident perspectives. Continuity
      requires balance between provider availability and demand for services.
      Optimizing this balance to maximize resident education, and the health of the
      population served, will require consideration of relevant local factors and
      priorities in addition to the clinic model.

PMID- 26217421
TI  - Concurrent Validity Between a Shared Curriculum, the Internal Medicine In
      Training Examination, and the American Board of Internal Medicine Certifying
      Examination.
AB  - BACKGROUND: A core objective of residency education is to facilitate learning,
      and programs need more curricula and assessment tools with demonstrated validity
      evidence. OBJECTIVE: We sought to demonstrate concurrent validity between
      performance on a widely shared, ambulatory curriculum (the Johns Hopkins Internal
      Medicine Curriculum), the Internal Medicine In-Training Examination (IM-ITE), and
      the American Board of Internal Medicine Certifying Examination (ABIM-CE).
      METHODS: A cohort study of 443 postgraduate year (PGY)-3 residents at 22 academic
      and community hospital internal medicine residency programs using the curriculum
      through the Johns Hopkins Internet Learning Center (ILC). Total and percentile
      rank scores on ILC didactic modules were compared with total and percentile rank
      scores on the IM-ITE and total scores on the ABIM-CE. RESULTS: The average score
      on didactic modules was 80.1%; the percentile rank was 53.8. The average IM-ITE
      score was 64.1% with a percentile rank of 54.8. The average score on the ABIM-CE
      was 464. Scores on the didactic modules, IM-ITE, and ABIM-CE correlated with each
      other (P < .05). Residents completing greater numbers of didactic modules,
      regardless of scores, had higher IM-ITE total and percentile rank scores (P <
      .05). Resident performance on modules covering back pain, hypertension,
      preoperative evaluation, and upper respiratory tract infection was associated
      with IM-ITE percentile rank. CONCLUSIONS: Performance on a widely shared
      ambulatory curriculum is associated with performance on the IM-ITE and the ABIM
      CE.

PMID- 26217422
TI  - The Perceived Effect of Duty Hour Restrictions on Learning Opportunities in the
      Intensive Care Unit.
AB  - BACKGROUND: Many countries have reduced resident duty hours in an effort to
      promote patient safety and enhance resident quality of life. There are concerns
      that reducing duty hours may impact residents' learning opportunities.
      OBJECTIVES: We (1) evaluated residents' perceptions of their current learning
      opportunities in a context of reduced duty hours, and (2) explored the perceived
      change in resident learning opportunities after call length was reduced from 24
      continuous hours to 16 hours. METHODS: We conducted an anonymous, cross-sectional
      online survey of 240 first-, second-, and third-year residents rotating through 3
      McGill University-affiliated intensive care units (ICUs) in Montreal, Quebec,
      Canada, between July 1, 2012, and June 30, 2013. The survey investigated
      residents' perceptions of learning opportunities in both the 24-hour and 16-hour
      systems. RESULTS: Of 240 residents, 168 (70%) completed the survey. Of these
      residents, 63 (38%) had been exposed to both 24-hour and 16-hour call schedules.
      The majority of respondents (83%) reported that didactic teaching sessions held
      by ICU staff physicians were useful. However, of the residents trained in both
      approaches to overnight call, 44% reported a reduction in learner attendance at
      didactic teaching sessions, 48% reported a reduction in attendance at midday
      hospital rounds, and 40% reported a perceived reduction in self-directed reading
      after the implementation of the new call schedule. CONCLUSIONS: A substantial
      proportion of residents perceived a reduction in the attendance of instructor
      directed and self-directed reading after the implementation of a 16-hour call
      schedule in the ICU.

PMID- 26217423
TI  - Online Versus In-Person Screening, Brief Intervention, and Referral to Treatment
      Training in Pediatrics Residents.
AB  - BACKGROUND: Pediatricians underestimate the prevalence of substance misuse among
      children and adolescents and often fail to screen for and intervene in practice.
      The American Academy of Pediatrics recommends training in Screening, Brief
      Intervention, and Referral to Treatment (SBIRT), but training outcomes and skill
      acquisition are rarely assessed. OBJECTIVE: We compared the effects of online
      versus in-person SBIRT training on pediatrics residents' knowledge, attitudes,
      behaviors, and skills. METHODS: Forty pediatrics residents were randomized to
      receive either online or in-person training. Skills were assessed by pre- and
      posttraining standardized patient interviews that were coded for SBIRT-adherent
      and -nonadherent behaviors and global skills by 2 trained coders. Thirty-two
      residents also completed pre- and postsurveys of their substance use knowledge,
      attitudes, and behaviors (KABs). Two-way repeated measures multivariate analyses
      of variance (MANOVAs) and analyses of variance (ANOVAs) estimates were used to
      assess group differences in skill acquisition and KABs. RESULTS: Findings
      indicated that both groups demonstrated skill improvement from pre- to
      postassessment. Results indicated that both groups increased their knowledge,
      self-reported behaviors, confidence, and readiness with no significant between
      group differences. Follow-up univariate analyses indicated that, while both
      groups increased their SBIRT-adherent skills, the online training group displayed
      more "undesirable" behaviors posttraining. CONCLUSIONS: The current study
      indicates that brief training, online or in-person, can increase pediatrics
      residents' SBIRT skills, knowledge, self-reported behaviors, confidence, and
      readiness. The findings further indicate that in-person training may have
      incremental benefit in teaching residents what not to do.

PMID- 26217424
TI  - Drug Testing Incoming Residents and Medical Students in Family Medicine Training:
      A Survey of Program Policies and Practices.
AB  - BACKGROUND: Despite well-established negative consequences, high rates of
      substance use and related disorders continue to be reported. Physicians in
      training are not immune from this, or the associated risks to their health and
      careers, while impaired physicians are a threat to patient safety. OBJECTIVE: We
      surveyed family medicine residency programs' practices relating to drug testing
      of medical students and incoming residents. The survey asked about the extent to
      which residency programs are confronted with trainees testing positive for
      prohibited substances, and how they respond. METHODS: The survey was sent to the
      directors of family medicine residency programs. A total of 205 directors (47.2%)
      completed the survey. RESULTS: A majority of the responding programs required
      drug testing for incoming residents (143, 68.9%). Most programs did not require
      testing of medical students (161, 81.7%). Few programs reported positive drug
      tests among incoming residents (9, 6.5%), and there was only 1 reported instance
      of a positive result among medical students (1, 3.3%). Respondents reported a
      range of responses to positive results, with few reporting that they would keep
      open training spots or offer supportive services for a medical student who tested
      positive. CONCLUSIONS: Changing laws legalizing certain drugs may require
      corresponding changes in the focus on drug testing and associated issues in
      medical training; however, many residency program directors were not aware of
      their institution's current policies. Programs will need to reexamine drug
      testing policies as new generations of physicians, growing up under altered legal
      circumstances concerning drug use, progress to clinical training.

PMID- 26217425
TI  - Comparing Hospitalist-Resident to Hospitalist-Midlevel Practitioner Team
      Performance on Length of Stay and Direct Patient Care Cost.
AB  - BACKGROUND: A perception exists that residents are more costly than midlevel
      providers (MLPs). Since graduate medical education (GME) funding is a key issue
      for teaching programs, hospitals should conduct cost-benefit analyses when
      considering staffing models. OBJECTIVE: Our aim was to compare direct patient
      care costs and length of stay (LOS) between resident and MLP inpatient teams.
      METHODS: We queried the University HealthSystems Consortium clinical database
      (UHC CDB) for 13 553 "inpatient" discharges at our institution from July 2010 to
      June 2013. Patient assignment was based on bed availability rather than
      "educational value." Using the UHC CDB data, discharges for resident and MLP
      inpatient teams were compared for observed and expected LOS, direct cost derived
      from hospital charges, relative expected mortality (REM), and readmissions. We
      also compared patient satisfaction for physician domain questions using Press
      Ganey data. Bivariate analysis was performed for factors associated with
      differences between the 2 services using chi(2) analysis and Student t test for
      categorical and continuous variables, respectively. RESULTS: During the 3-year
      period, while REM was higher on the hospitalist-resident services (P < .001), LOS
      was shorter by 1.26 days, and per-patient direct costs derived from hospital
      charges were lower by $617. Patient satisfaction scores for the physician
      selected questions were higher for resident teams. There were no differences in
      patient demographics, daily discharge rates, readmissions, or deaths.
      CONCLUSIONS: Resident teams are economically more efficient than MLP teams and
      have higher patient satisfaction. The findings offer guidance when considering
      GME costs and inpatient staffing models.

PMID- 26217427
TI  - Milestone-Based Assessments Are Superior to Likert-Type Assessments in
      Illustrating Trainee Progression.
AB  - BACKGROUND: The Pediatrics Milestone Project uses behavioral anchors, narrative
      descriptions of observable behaviors, to describe learner progression through the
      Accreditation Council for Graduate Medical Education competencies. Starting June
      2014, pediatrics programs were required to submit milestone reports for their
      trainees semiannually. Likert-type scale assessment tools were not designed to
      inform milestone reporting, creating a challenge for Clinical Competency
      Committees. OBJECTIVE: To determine if milestone-based assessments better
      stratify trainees by training level compared to Likert-type assessments. METHODS:
      We compared assessment results for 3 subcompetencies after changing from a 5
      point Likert scale to milestone-based behavioral anchors in July 2013. Program
      leadership evaluated the new system by (1) comparing PGY-1 mean scores on Likert
      type versus milestone-based assessments; and (2) comparing mean scores on the
      Likert-type versus milestone-based assessments across PGY levels. RESULTS: Mean
      scores for PGY-1 residents were significantly higher on the prior year's Likert
      type assessments than milestone-based assessments for all 3 subcompetencies (P <
      .01). Stratification by PGY level was not observed with Likert-type assessments
      (eg, interpersonal and communication skills 1 [ICS1] mean score for PGY-1, 3.99
      versus PGY-3, 3.98; P  =  .98). In contrast, milestone-based assessments
      demonstrated stratification by PGY level (eg, the ICS1 mean score was 3.06 for
      PGY-1, 3.83 for PGY-2, and 3.99 for PGY-3; P < .01 for PGY-1 versus PGY-3).
      Significantly different means by trainee level were noted across 21
      subcompetencies on milestone-based assessments (P < .01 for PGY-1 versus PGY-3).
      CONCLUSIONS: Initial results indicate milestone-based assessments stratify
      trainee performance by level better than Likert-type assessments. Average PGY
      level scores from milestone-based assessments may ultimately provide guidance for
      determining whether trainees are progressing at the expected pace.

PMID- 26217426
TI  - Predictors of Well-Being in Resident Physicians: A Descriptive and Psychometric
      Study.
AB  - BACKGROUND: It is important to describe the characteristics of well-being in
      resident physicians to develop resident wellness initiatives in postgraduate
      medical education. OBJECTIVE: To characterize the predictors of well-being in
      resident physicians by assessing personal and work-related burnout, work
      dissatisfaction, nutritional needs while on call, and sleep needs while on call.
      METHODS: We set up an online survey in 2012 to collect data from current
      residents at the University of Calgary in Canada. The WHO-Five Well-Being Index,
      personal and work-related subscales of the Copenhagen Burnout Inventory,
      questions on work dissatisfaction, as well as sleep and nutrition management
      needs while on call, were used in the survey. Descriptive statistics, univariate
      analysis, and linear regression were applied to the data. RESULTS: The survey
      response rate was 45% (317 of 706) of eligible residents, with a mean age of 30.9
      years (SD  =  4.3). Fifty-three percent (168 of 317) of residents had a well
      being score of 13 or less, indicating poor mental well-being. There were
      significant differences between men and women with respect to personal burnout
      (47.9 versus 54.2, P  =  .002) and work-related burnout (46.4 versus 50.4, P  = 
      .008). The only significant predictors of well-being overall were personal
      burnout and work dissatisfaction. CONCLUSIONS: Survey results suggest that a high
      proportion of residents at this institution have low well-being. This study did
      not find work-related burnout to be a significant predictor of well-being, after
      adjustment for other variables.

PMID- 26217428
TI  - Relationship Between the Number of Residency Applications and the Yearly Match
      Rate: Time to Start Thinking About an Application Limit?
AB  - BACKGROUND: There has been an increase in the number of applications medical
      students have submitted for the National Residency Matching Program (NRMP). These
      additional applications are associated with significant costs and may contribute
      to match inefficiency. OBJECTIVE: We explored if match rates improved in years
      when an increased number of applications were submitted. METHODS: We analyzed
      yearly published data from the NRMP and the Electronic Residency Application
      Service for 13 specialties. A generalized linear model was used to assess the
      relationship between the annual match rate and the mean number of applications
      submitted per applicant, while controlling for the number of positions available
      and the number of applicants in the given year. RESULTS: Over the last 13 years
      there has been an increase in the mean number of applications submitted per
      applicant (P < .001). For the 13 assessed medical specialties, there was no
      statistically significant relationship between the mean number of applications
      per applicant per year submitted to the NRMP, and the annual match rate (odds
      ratios near 1.00 and nonsignificant, P values > .05). CONCLUSIONS: There was no
      improvement in the match rate in years when medical students submitted an
      increased number of applications. Therefore, it would appear that the applicants
      do not benefit from the larger number of applications submitted. Further study is
      required to assess the cost and benefit of these additional applications.

PMID- 26217429
TI  - Meeting Resident Scholarly Activity Requirements Through a Longitudinal Quality
      Improvement Curriculum.
AB  - BACKGROUND: Quality improvement (QI) skills are learned during residency, yet
      there are few reports of the scholarly activity outcomes of a QI curriculum in a
      primary care program. INTERVENTION: We examined whether scholarly activity can
      result from a longitudinal, experiential QI curriculum that involves residents,
      clinic staff, and faculty. METHODS: The University of Pittsburgh Medical Center
      Shadyside Family Medicine Residency implemented a required longitudinal
      outpatient practice improvement rotation (LOPIR) curriculum in 2005. The rotation
      format includes weekly multidisciplinary work group meetings alternating with
      resident presentations delivered to the entire program. Residents present the
      results of a literature review and provide 2 interim project updates to the
      residency. A completed individual project is required for residency graduation,
      with project results presented at Residency Research Day. Scholarly activity
      outcomes of the curriculum were analyzed using descriptive statistics. RESULTS:
      As of 2014, 60 residents completed 3 years of the LOPIR curriculum. All residents
      satisfied the 2014 Accreditation Council for Graduate Medical Education (ACGME)
      scholarly activity and QI requirements with a literature review presentation in
      postgraduate year 2, and the presentation of a completed QI project at Residency
      Research Day. Residents have delivered 83 local presentations, 13 state/regional
      presentations, and 2 national presentations. Residents received 7 awards for QI
      posters, as well as 3 grants totaling $21,639. The educational program required
      no additional curriculum time, few resources, and was acceptable to residents,
      faculty, and staff. CONCLUSIONS: LOPIR is an effective way to meet and exceed the
      2014 ACGME scholarly activity requirements for family medicine residents.

PMID- 26217430
TI  - Advanced Care Directives: Overcoming the Obstacles.
AB  - BACKGROUND: Advanced care directives (ACDs) and end-of-life discussions are
      important and typically difficult to initiate because of the sensitive nature of
      the topic and competing clinical priorities. Resident physicians need to have
      these conversations but often do not in their continuity clinics. OBJECTIVE: We
      implemented a program to (1) increase physician opportunity to discuss end-of
      life wishes with their patients, and (2) improve residents' confidence in leading
      discussions regarding ACDs. INTERVENTION: A total of 95 residents in an academic
      outpatient internal medicine resident continuity clinic participated in a
      formalized curriculum (didactic sessions, simulations, and academic detailing).
      Clinic workflow alterations prompted the staff to question if patients had an ACD
      or living will, and then cued residents to discuss these issues with the patients
      if they did not. RESULTS: Of the 77% of patients who were asked about ACDs, 74%
      had no ACD but were interested in discussing this topic. After our intervention,
      65% (62 of 95) of our residents reported having at least 1 outpatient discussion
      with their patients. Residents reported increased confidence directing and
      discussing advanced care planning with older patients and conducting a family
      meeting (P < .01). CONCLUSIONS: By delivering a formalized curriculum and
      creating a clinical environment that supports such discussions, resident
      physicians had more ACD discussions with their patients and reported increased
      confidence. When provided information and opportunity, patients consistently
      expressed interest in talking with their physician about their advanced care
      wishes.

PMID- 26217431
TI  - Using Standardized Patients to Teach Point-of-Care Ultrasound-Guided Physical
      Examination Skills to Internal Medicine Residents.
AB  - BACKGROUND: Point-of-care (POC) ultrasound has been shown to improve procedural
      outcomes and physical examination accuracy in multiple settings. There are
      limited data regarding the optimal way to train nonradiologists in POC
      ultrasound. This is a primary barrier to more widespread use of ultrasound in the
      physical examination. OBJECTIVE: We created a workshop to instruct postgraduate
      year (PGY)-2 and PGY-3 internal medicine residents in POC ultrasound imaging of
      the abdominal aorta and kidneys. METHODS: A half-day simulation center workshop
      was created to review ultrasound operations and teach residents to independently
      obtain ultrasound images of the abdominal aorta and kidneys on standardized
      patients with normal anatomy. The workshop incorporated didactic instruction and
      hands-on ultrasound practice in small groups. Each resident's ability to
      independently obtain ultrasound images was assessed using a preworkshop and
      postworkshop skills examination with a standardized patient. Resident knowledge
      and attitudes toward POC ultrasound were also assessed using a preworkshop and
      postworkshop test and survey. RESULTS: A total of 58 residents completed the
      workshop, and 84% were able to independently obtain high-quality images of the
      abdominal aorta and kidney after workshop completion, compared with 16% on the
      preworkshop test. Residents demonstrated a statistically significant increase in
      their self-reported confidence with ultrasound operation and image acquisition.
      CONCLUSIONS: Training using standardized patients can prepare residents to
      independently obtain POC ultrasound images of the aorta and kidneys. Training
      resulted in increased resident confidence with POC ultrasound and self-reported
      likelihood of future use.

PMID- 26217432
TI  - Clinical Skills Assessment: The Effects of Moving Certification Requirements Into
      Neurology, Child Neurology, and Psychiatry Residency Training.
AB  - BACKGROUND: A few years ago, when the American Board of Psychiatry and Neurology
      decided to phase out the patient-based oral examinations in its 3 primary
      specialties, requirements for assessing clinical skills during residency training
      were instituted. OBJECTIVE: The purpose of this report is to describe the
      experiences of training program directors and graduates with these new
      credentialing requirements (labeled CSEs) as well as other effects on the
      specialties. METHODS: Surveys were administered electronically in 2012 to all
      current neurology, child neurology, and psychiatry program directors, and to a
      convenience sample of graduates who applied for the 2012 certification
      examinations. RESULTS: Response rates for graduates were similar across the 3
      specialties but low (28%-33%). Response rates were higher for program directors
      (53%-62%) and were similar across the 3 specialties. The results indicated that
      the CSEs were usually administered early in training, were completed toward the
      end, were often passed on first attempt, generally took place during routine
      clinical assignments, were used to assess additional competencies, almost always
      included feedback to the residents, and did not often lead to remediation.
      Furthermore, the CSEs were perceived to be useful components in the assessment of
      clinical skills. CONCLUSIONS: The results obtained from the early implementation
      of the CSEs suggest that they provide an opportunity to assess clinical skills
      with the additional benefit of feedback to trainees. Other effects included
      eventual incorporation into training program requirements, milestones, and
      related faculty development and research efforts.

PMID- 26217433
TI  - Use of Milestones and Development of Entrustable Professional Activities in 2
      Hematology/Oncology Training Programs.
AB  - BACKGROUND: The Next Accreditation System (NAS) increases the focus on
      educational outcomes and meaningful evaluation of learners. This requires that
      key clinical faculty develop new assessment formats such as entrustable
      professional activities (EPAs). OBJECTIVES: To build and develop milestone-based
      assessment tools supporting 5 EPAs for a hematology/oncology fellow continuity
      clinic, and to educate key clinical faculty regarding the Clinical Competency
      Committee (CCC) and the NAS. METHODS: Program directors from 2
      hematology/oncology fellowship programs developed 5 EPAs for continuity clinic
      evaluation supported by milestone-based assessment. The program directors met to
      create a unified CCC charter. Key clinical faculty helped to develop a milestone
      based evaluation of fellow continuity clinic through creation of 5
      hematology/oncology-specific EPAs. Formal entrustment regarding EPAs was
      deliberated by the CCC. RESULTS: A total of 18 fellows were evaluated. Clinical
      Competency Committee deliberation at each institution took approximately 10
      minutes per fellow for discussion and decision regarding entrustment for all 5
      EPAs supporting continuity clinic. One-third of postgraduate year (PGY)-4s, 50%
      of PGY-5s, and 100% of PGY-6s were deemed competent in all 5 EPAs by the CCC.
      CONCLUSIONS: All hematology/oncology trainees in San Antonio were evaluated using
      milestone-based assessment for continuity clinic, and entrustment decisions
      regarding 5 EPAs were made by the CCC. This project may provide other programs
      with a sound basis for adoption and further development of the next generation of
      evaluation tools at their institutions. Entrustable professional activities that
      are rotation specific should be used as a starting point for linking to the
      competencies, subcompetencies, and the reporting milestones.

PMID- 26217434
TI  - Results of a Formal Mentorship Program for Internal Medicine Residents: Can We
      Facilitate Genuine Mentorship?
AB  - BACKGROUND: Mentorship programs are perceived as valuable, yet little is known
      about the effect of program design on mentoring effectiveness. INTERVENTION: We
      developed a program focused on mentoring relationship quality and evaluated how
      subsequent relationships compared to preexisting informal pairings. METHODS:
      Faculty members were invited by e-mail to participate in a new mentoring program.
      Participants were asked to complete a biography, subsequently provided to second-
      and third-year internal medicine residents. Residents were instructed to contact
      available mentors, and ultimately designate a formal mentor. All faculty and
      residents were provided a half-day workshop training, written guidelines, and e
      mails. Reminders were e-mailed and announced in conferences approximately
      monthly. Residents were surveyed at the end of the academic year. RESULTS: Thirty
      seven faculty members completed the biography, and 70% (26 of 37) of residents
      responded to the survey. Of the resident respondents, 77% (20 of 26) chose a
      formal mentor. Of the remainder, most had a previous informal mentor. Overall,
      96% (25 of 26) of the residents had identified a mentor of some kind compared to
      50% (13 of 26) before the intervention (P < .001), and 70% (14 of 20) who chose
      formal mentors identified them as actual mentors. Similar numbers of residents
      described their mentors as invested in the mentorship, and there was no
      statistical difference in the number of times mentors and mentees met.
      CONCLUSIONS: Facilitated selection of formal mentors produced relationships
      similar to preexisting informal ones. This model may increase the prevalence of
      mentorship without decreasing quality.

PMID- 26217435
TI  - Evaluating the Clinical Learning Environment: Resident and Fellow Perceptions of
      Patient Safety Culture.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education has begun to
      evaluate teaching institutions' learning environments with Clinical Learning
      Environment Review visits, including trainee involvement in institutions' patient
      safety and quality improvement efforts. OBJECTIVE: We sought to address the
      dearth of metrics that assess trainee patient safety perceptions of the clinical
      environment. METHODS: Using the Hospital Survey on Patient Safety Culture
      (HSOPSC), we measured resident and fellow perceptions of patient safety culture
      in 50 graduate medical education programs at 10 hospitals within an integrated
      health system. As institution-specific physician scores were not available,
      resident and fellow scores on the HSOPSC were compared with national data from 29
      162 practicing providers at 543 hospitals. RESULTS: Of the 1337 residents and
      fellows surveyed, 955 (71.4%) responded. Compared with national practicing
      providers, trainees had lower perceptions of patient safety culture in 6 of 12
      domains, including teamwork within units, organizational learning, management
      support for patient safety, overall perceptions of patient safety, feedback and
      communication about error, and communication openness. Higher perceptions were
      observed for manager/supervisor actions promoting patient safety and for
      staffing. Perceptions equaled national norms in 4 domains. Perceptions of patient
      safety culture did not improve with advancing postgraduate year. CONCLUSIONS:
      Trainees in a large integrated health system have variable perceptions of patient
      safety culture, as compared with national norms for some practicing providers.
      Administration of the HSOPSC was feasible and acceptable to trainees, and may be
      used to track perceptions over time.

PMID- 26217436
TI  - The Courteous Consult: A CONSULT Card and Training to Improve Resident Consults.
AB  - BACKGROUND: Communication and courtesy are important elements of consultations,
      but there is limited published data about the quality of trainee consults.
      OBJECTIVES: This study assessed residents' views on consult interactions,
      evaluated the impact of the consult interactions on patient care, and developed
      and implemented a pocket card and training on trainee consults. METHODS: We
      surveyed resident and fellow physicians at Mount Sinai Hospital to assess
      perceptions, created a CONSULT card that uses a mnemonic for key elements, and
      developed a training session for how to call consults. We also conducted a
      consult training session using the CONSULT card as part of orientation in 2011
      for all interns. We assessed the acceptability, feasibility, and sustainability
      of this intervention. RESULTS: Of 1001 trainees, 403 (40%) responded. Respondents
      reported that the most important components of calling consults included giving
      patient name, medical record number, and location (91%), and giving a clear
      question/reason (89%). Respondents also reported that these behaviors are done
      consistently for only 64%, and 10% of consults, respectively. Trainees reported
      that consult interactions affect the timeliness of treatment (62%), timeliness of
      tests performed (57%), appropriateness of diagnosis (56%), and discharge planning
      (49%). Approximately 300 interns attended the consult training session, and their
      feedback demonstrated acceptability and utility of the session. CONCLUSIONS:
      Trainees believe that consult interactions impact patient care, but important
      components of the consult call are often missing. Our training and CONSULT card
      is an acceptable, feasible, and novel training intervention. Once developed, the
      training session and CONSULT card require minimal faculty time to deliver.

PMID- 26217437
TI  - Promoting Resident Involvement in Quality Improvement Initiatives Through Faculty
      Involvement and Curriculum.

PMID- 26217438
TI  - Continuity and Darwinism-Natural Selection, Extinction, or Adaptation.

PMID- 26217439
TI  - A "Sound" Approach.

PMID- 26217440
TI  - Opening the "Black Box" of GME Costs and Benefits: A Conceptual Model and a Call
      for Systematic Studies.

PMID- 26217441
TI  - Prevalence of Drug Testing Among Family Medicine Residents and Students: Much
      Needed Data.

PMID- 26217442
TI  - Beyond the "July Effect".

PMID- 26217443
TI  - Humanism, Compassion, and Afternoon Tea in Medical Education.

PMID- 26217444
TI  - A Measured Approach to Enhancing the Nonclinical Skills of US MDs.

PMID- 26217445
TI  - The Residency Interview Scheduling Process: Unintended Consequences and a
      Proposal for Change.

PMID- 26217447
TI  - Gold Humanism Honor Society Membership Indicator to Be Added to ERAS Applications
      Beginning With 2016 Application Cycle.

PMID- 26217448
TI  - There Is No Denying It, Our Medical Language Needs an Update.

PMID- 26217449
TI  - Medicine in 2035: Selected Insights From ACGME's Scenario Planning.
AB  - The Accreditation Council for Graduate Medical Education (ACGME) has the
      responsibility for overseeing the preparation of future physician specialists and
      subspecialists to serve the American public. To ensure ACGME's ability to adapt
      and sustain its accreditation activities in a future marked by significant
      uncertainty, its administration and board of directors embarked on a planning
      process that would frame its strategic actions in support of this responsibility.
      We describe the scenario planning process, and report key insights that resulted
      from it. We also discuss in greater depth a subset of those insights, which
      challenge certain conventional truths, call for new collaborative directions for
      the ACGME, and reaffirm the importance of professionalism in service of the
      public across all future scenarios evaluated. 

PMID- 26217450
TI  - Promotion of Wellness and Mental Health Awareness Among Physicians in Training:
      Perspective of a National, Multispecialty Panel of Residents and Fellows.
AB  - BACKGROUND: Physicians in training are at high risk for depression, and
      physicians in practice have a substantially elevated risk of suicide compared to
      the general population. The graduate medical education community is currently
      mobilizing efforts to improve resident wellness. OBJECTIVE: We sought to provide
      a trainee perspective on current resources to support resident wellness and
      resources that need to be developed to ensure an optimal learning environment.
      METHODS: The ACGME Council of Review Committee Residents, a 29-member
      multispecialty group of residents and fellows, conducted an appreciative inquiry
      exercise to (1) identify existing resources to address resident wellness; (2)
      envision the ideal learning environment to promote wellness; and (3) determine
      how the existing infrastructure could be modified to approach the ideal. The
      information was aggregated to identify consensus themes from group discussion.
      RESULTS: National policy on resident wellness should (1) increase awareness of
      the stress of residency and destigmatize depression in trainees; (2) develop
      systems to identify and treat depression in trainees in a confidential way to
      reduce barriers to accessing help; (3) enhance mentoring by senior peers and
      faculty; (4) promote a supportive culture; and (5) encourage additional study of
      the problem to deepen our understanding of the issue. CONCLUSIONS: A
      multispecialty, national panel of trainees identified actionable goals to broaden
      efforts in programs and sponsoring institutions to promote resident wellness and
      mental health awareness. Engagement of all stakeholders within the graduate
      medical education community will be critical to developing a comprehensive
      solution to this important issue.

PMID- 26217452
TI  - Erratum.

PMID- 26217453
TI  - Endovascular management of visceral artery aneurysms: When to watch, when to
      intervene?
AB  - Visceral artery aneurysms (VAA) include splanchnic and renal artery aneurysms.
      They represent a rare clinical entity, although their detection is rising due to
      an increased use of cross-sectional imaging. Rupture is the most devastating
      complication, and is associated with a high morbidity and mortality. In addition,
      increased percutaneous endovascular interventions have raised the incidence of
      iatrogenic visceral artery pseudoaneurysms (VAPAs). For this reason, elective
      repair is preferable in the appropriately chosen patient. Controversy still
      exists regarding their treatment. Over the past decade, there has been steady
      increase in the utilization of minimally invasive, non-operative interventions,
      for vascular aneurysmal disease. All VAAs and VAPAs can technically be fixed by
      endovascular techniques but that does not mean they should. These catheter-based
      techniques constitute an excellent approach in the elective setting. However, in
      the emergent setting it may carry a higher morbidity and mortality. The decision
      for intervention has to take into account the size and the natural history of the
      lesion, the risk of rupture, which is high during pregnancy, and the relative
      risk of surgical or radiological intervention. For splanchnic artery aneurysms,
      we should recognize that we are not, in reality, well informed about their
      natural history. For most asymptomatic aneurysms, expectant treatment is
      acceptable. For large, symptomatic or aneurysms with a high risk of rupture,
      endovascular treatment has become the first-line therapy. Treatment of VAPAs is
      always mandatory because of the high risk of rupture. We present our point of
      view on interventional radiology in the splanchnic arteries, focusing on what has
      been achieved and the remaining challenges. 

PMID- 26217454
TI  - Diffusion-weighted and diffusion-tensor imaging of normal and diseased uterus.
AB  - Owing to technical advances and improvement of the software, diffusion weighted
      imaging and diffusion tensor imaging (DWI and DTI) greatly improved the
      diagnostic value of magnetic resonance imaging (MRI) of the pelvic region. These
      imaging sequences can exhibit important tissue contrast on the basis of random
      diffusion (Brownian motion) of water molecules in tissues. Quantitative
      measurements can be done with DWI and DTI by apparent diffusion coefficient (ADC)
      and fractional anisotropy (FA) values respectively. ADC and FA values may be
      changed by various physiological and pathological conditions providing additional
      information to conventional MRI. The quantitative DWI assists significantly in
      the differentiation of benign and malignant lesions. It can demonstrate the
      microstructural architecture and celluler density of the normal and diseased
      uterine zones. On the other hand, DWI and DTI are useful for monitoring the
      treatment outcome of the uterine lesions. In this review, we discussed advantages
      of DWI and DTI of the normal and diseased uterus. 

PMID- 26217456
TI  - Perfusion computed tomography in renal cell carcinoma.
AB  - Various imaging modalities are available for the diagnosis, staging and response
      evaluation of patients with renal cell carcinoma (RCC). While contrast enhanced
      computed tomography (CT) is used as the standard of imaging for size,
      morphological evaluation and response assessment in RCC, a new functional imaging
      technique like perfusion CT (pCT), goes down to the molecular level and provides
      new perspectives in imaging of RCC. pCT depicts regional tumor perfusion and
      vascular permeability which are indirect parameters of tumor angiogenesis and
      thereby provides vital information regarding tumor microenvironment. Also
      response evaluation using pCT may predate the size criteria used in Response
      Evaluation Criteria in Solid Tumors, as changes in the perfusion occurs earlier
      following tissue kinase inhibitors before any actual change in size. This may
      potentially help in predicting prognosis, better selection of therapy and more
      accurate and better response evaluation in patients with RCC. This article
      describes the techniques and role of pCT in staging and response assessment in
      patients with RCCs. 

PMID- 26217455
TI  - Non-invasive diagnostic imaging of colorectal liver metastases.
AB  - Colorectal cancer is one of the few malignant tumors in which synchronous or
      metachronous liver metastases [colorectal liver metastases (CRLMs)] may be
      treated with surgery. It has been demonstrated that resection of CRLMs improves
      the long-term prognosis. On the other hand, patients with un-resectable CRLMs may
      benefit from chemotherapy alone or in addition to liver-directed therapies. The
      choice of the most appropriate therapeutic management of CRLMs depends mostly on
      the diagnostic imaging. Nowadays, multiple non-invasive imaging modalities are
      available and those have a pivotal role in the workup of patients with CRLMs.
      Although extensive research has been performed with regards to the diagnostic
      performance of ultrasonography, computed tomography, positron emission tomography
      and magnetic resonance for the detection of CRLMs, the optimal imaging strategies
      for staging and follow up are still to be established. This largely due to the
      progressive technological and pharmacological advances which are constantly
      improving the accuracy of each imaging modality. This review describes the non
      invasive imaging approaches of CRLMs reporting the technical features, the
      clinical indications, the advantages and the potential limitations of each
      modality, as well as including some information on the development of new imaging
      modalities, the role of new contrast media and the feasibility of using
      parametric image analysis as diagnostic marker of presence of CRLMs. 

PMID- 26217457
TI  - Isolated renal hydatid presenting as a complex renal lesion followed by
      spontaneous hydatiduria.
AB  - Echinococcosis is a zoonotic disease. Liver is the most common site of
      involvement. Renal involvement is seen in 2% to 3% of patients. Computed
      tomography findings in renal hydatid typically include: a cyst with thick or
      calcified wall, unilocular cyst with detached membrane, a multiloculated cyst
      with mixed internal density and daughter cysts with lower density than maternal
      matrix. Rarely type IV hydatid cysts may mimic hypovascular renal cell carcinoma.
      We report a case of previously asymptomatic middle aged female who presented with
      mild intermittent pain and a complex renal lesion on imaging which was considered
      to be a hypovascular renal carcinoma or urothelial neoplasm. However, by
      serendipity, the patient had spontaneous hydatiduria and later was definitively
      diagnosed and stented. Hydatid disease should always be considered amongst the
      top differential diagnosis of an isolated "complex" renal lesion which remains
      indeterminate on imaging. 

PMID- 26217458
TI  - Twenty-Year Experience of a Double-Bundle Anterior Cruciate Ligament
      Reconstruction.
AB  - Double-bundle (DB) anterior cruciate ligament (ACL) reconstruction using a four
      strand semitendinosus tendon was started in our department in July 1994. The
      motivation for starting the procedure was that the EndoButton with an inside-out
      procedure instrument became available in Japan. A review article of our DB ACL
      reconstruction procedure was summarized for the twentieth anniversary of the
      surgical procedure. Initial tension setting of the two grafts was changed in the
      first 8 years to achieve better stability during DB ACL reconstruction. A
      randomized clinical trial (RCT) was started in July 2002 to clarify superiority
      of the DB procedure to single-bundle (SB) reconstruction under the concept of
      anatomic reconstruction. Several anatomic studies were performed to describe
      normal ACL anatomy, which is essential for realizing anatomic reconstruction. A
      remnant-preserving technique would be an additional option for our DB procedure
      to improve reconstruction outcomes. Thus, a new remnant-preserving DB procedure
      was started in 2012. The reproducibility of the new procedure was investigated
      using three-dimensional computed tomography images. More complex procedures were
      performed using a transtibial technique and EndoButtons. Initial tension
      balancing between the two grafts was important for a better outcome. Superiority
      of knee stability after the DB compared to that after the SB procedure was
      clarified by the RCT. However, no patient consensus has been reached on any
      subjective advantage to the DB procedure. Studies of normal ACL anatomy have left
      questions unresolved regarding where the two tunnels should be created for direct
      and indirect insertions based on normal anatomy. A new remnant-preserving DB ACL
      procedure has been practiced. The procedure was more reproducible with respect to
      creating the femoral tunnel. DB ACL reconstruction using a semitendinosus tendon
      is an attractive option when pursuing a better outcome for patients. 

PMID- 26217459
TI  - Accurate and Easy Measurement of Sliding Distance of Intramedullary Nail in
      Trochanteric Fracture.
AB  - BACKGROUND: In daily clinical practice, it is essential to properly evaluate the
      postoperative sliding distance of various femoral head fixation devices (HFD) for
      trochanteric fractures. Although it is necessary to develop an accurate and
      reproducible method that is unaffected by inconsistent postoperative limb
      position on radiography, few studies have examined which method is optimal.
      Therefore, the purpose of this study is to prospectively compare the accuracy and
      reproducibility of our four original methods in the measurement of sliding
      distance of the HFD. METHODS: Radiographs of plastic simulated bone implanted
      with Japanese proximal femoral nail antirotation were taken in five limb
      postures: neutral, flexion, minute internal rotation, greater external rotation,
      and flexion with external rotation. Orthopedic surgeons performed five
      measurements of the sliding distance of the HFD in each of the flowing four
      methods: nail axis reference (NAR), modified NAR, inner edge reference, and nail
      tip reference. We also assessed two clinical cases by using these methods and
      evaluated the intraclass correlation coefficients. RESULTS: The measured values
      were consistent in the NAR method regardless of limb posture, with an even
      smaller error when using the modified NAR method. The standard deviation (SD) was
      high in the nail tip reference method and extremely low in the modified NAR
      method. In the two clinical cases, the SD was the lowest in the modified NAR
      method, similar to the results using plastic simulated bone. The intraclass
      correlation coefficients showed the highest value in the modified NAR method.
      CONCLUSIONS: We conclude that the modified NAR method should be the most
      recommended based on its accuracy, reproducibility, and usefulness.

PMID- 26217460
TI  - Arthroscopic Treatment of Symptomatic Internal Snapping Hip with Combined
      Pathologies.
AB  - BACKGROUND: Arthroscopic iliopsoas tendon release was introduced in 2000. The
      purpose of this study was to evaluate clinical outcomes of arthroscopic iliopsoas
      tendon release for painful internal snapping hip with concomitant hip
      pathologies. METHODS: Between January 2009 and December 2011, we performed
      arthroscopic iliopsoas tendon release and related surgeries in 25 patients (20
      men and 5 women; mean age, 32 years; range, 17 to 53 years) with combined
      intraarticular hip pathologies. The patients were followed for a minimum of 2
      years postoperatively. Clinical and radiological evaluations were performed.
      RESULTS: Snapping sounds had disappeared by the 2-year follow-up in 24 of the 25
      patients. All patients who had presented with loss of flexion strength
      postoperatively showed recovery at postoperative week 6 to 10. Harris hip score
      improved from 65 points (range, 46 to 86 points) preoperatively to 84 points
      (range, 67 to 98 points) postoperatively (p < 0.001). Seven hips (28%) had an
      excellent score, 15 hips (60%) a good score, 2 hips (8%) a fair score, and one
      hip (4%) a poor score (p < 0.001). The Tonnis grade of osteoarthritis did not
      change in any of the patients at the last follow-up. CONCLUSIONS: Patients with
      painful internal snapping hip have combined hip pathologies. Therefore, the
      surgeon should keep in mind that painful internal snapping hips are frequently
      combined with concomitant intraarticular pathologies.

PMID- 26217461
TI  - Comparison of Continuous Epidural Analgesia, Patient-Controlled Analgesia with
      Morphine, and Continuous Three-in-One Femoral Nerve Block on Postoperative
      Outcomes after Total Hip Arthroplasty.
AB  - BACKGROUND: Postoperative pain relief can be achieved with various modalities.
      However, there are only few reports that have analyzed postoperative analgesic
      techniques in total hip arthroplasty patients. The aim of this retrospective
      study was to compare the postoperative outcomes of three different analgesic
      techniques after total hip arthroplasty. METHODS: We retrospectively reviewed the
      influence of three analgesic techniques on postoperative rehabilitation after
      total hip arthroplasty in 90 patients divided into three groups (n = 30 patients
      per group). Postoperative analgesia consisted of continuous epidural analgesia
      (Epi group), patient-controlled analgesia with morphine (PCA group), or a
      continuous femoral nerve block (CFNB group). We measured the following parameters
      relating to postoperative outcome: visual analog scale scores, the use of
      supplemental analgesia, side effects, length of the hospital stay, plasma D-dimer
      levels, and the Harris hip score. RESULTS: Each group had low pain scores with no
      significant differences between the groups. The PCA group had a lower frequency
      of supplemental analgesia use compared to the Epi and CFNB groups. Side effects
      (nausea/vomiting, inappetence) and day 7 D-dimer levels were significantly lower
      in the CFNB group (p < 0.05). There were no significant differences between the
      groups in terms of the length of the hospital stay or the Harris hip score.
      CONCLUSIONS: Although there were no clinically significant differences in
      outcomes between the three groups, the CFNB provided good pain relief which was
      equal to that of the other analgesics with fewer side effects and lower D-dimer
      levels in hospitalized patients following total hip arthroplasty.

PMID- 26217462
TI  - The Avon Patellofemoral Joint Replacement: Mid-Term Prospective Results from an
      Independent Centre.
AB  - BACKGROUND: Approximately 10% of patients with osteoarthritis (OA) of the knee
      have unicompartmental OA confined to the patellofemoral joint (PFJ). The main
      surgical options are total knee replacement (TKR) and PFJ replacement (PFJR).
      PFJR has a number of advantages over TKR, including being less invasive,
      preserving the unaffected parts of the knee, allowing faster recovery and better
      range of motion and function. We report our prospective mid-term results of the
      Avon PFJR for established isolated PFJ arthritis in 61 consecutive procedures.
      METHODS: Sixty-one Avon PFJRs were performed in 57 patients. The outcome measures
      were the new Oxford knee score (OKS), Hungerford and Kenna score (HKS), and
      Crosby Insall knee scores. Only patients with severe isolated PFJ OA were
      included. The diagnosis was based on a combination of clinical, radiological and,
      where available, arthroscopic findings. RESULTS: Mean follow-up was 5.09 years
      (range, 12 to 124 years). There were 2 revisions in the first 5 years. The median
      HKS score was 80 (interquartile range, 70 to 95) and the mean OKS was 31.8 (+/-
      standard deviation, 8.7) at 5 years. These were significantly better (p < 0.001)
      than the preoperative scores. CONCLUSIONS: The Avon prosthesis gives good
      functional outcomes in the medium term and survives well. Our data support other
      studies in the literature and is the largest independent prospective study to
      date.

PMID- 26217463
TI  - The Results of All-Inside Meniscus Repair Using the Viper Repair System
      Simultaneously with Anterior Cruciate Ligament Reconstruction.
AB  - BACKGROUND: Meniscus tears are commonly associated with anterior cruciate
      ligament (ACL) ruptures. It is essential to repair meniscal tears as much as
      possible to prevent early osteoarthritis and to gain additional stability in the
      knee joint. We evaluated the results of arthroscopic all-inside repair using the
      Meniscal Viper Repair System (Arthrex) on meniscus tears simultaneously with ACL
      reconstruction. METHODS: Nineteen out of 22 patients who were treated with
      arthroscopic all-inside repair using the Meniscal Viper Repair System for
      meniscus tear associated with ACL rupture were evaluated. ACL reconstructions
      were performed at the same period. The mean follow-up period was 16.5 months
      (range, 12 to 24 months). The clinical results of the meniscus repair were
      evaluated by symptoms (such as catching or locking), tenderness, effusion, range
      of motion limitation, and the McMurray test. Clinical success was defined by
      negative results in all five categories. The Hospital for Special Surgery (HSS)
      score was evaluated. Objective results were evaluated with secondary look
      arthroscopy or magnetic resonance imaging (MRI). The MRI results were categorized
      as completely repaired, incompletely repaired, and failure by Henning's
      classification. The results of second-look arthroscopy were evaluated with the
      criteria of meniscal healing. RESULTS: The clinical success rate was 95.4% and
      the HSS scores were 93.9 +/- 5.4 at the final follow-up. According to Henning's
      classification, 15 out of 18 cases showed complete healing (83.3%) and two cases
      (11.1%) showed incomplete healing. Seventeen out of 18 cases that underwent
      second-look arthroscopy showed complete healing (94.4%) according to the criteria
      of meniscal healing. Only one case showed failure and the failure was due to a re
      rupture at the sutured area. Complications of ACL reconstruction or meniscus
      repair were not present. CONCLUSIONS: The results demonstrate that arthroscopic
      all-inside repair using the Meniscal Viper Repair System is an effective
      treatment method when it is performed simultaneously with ACL reconstruction.

PMID- 26217464
TI  - Biplanar Open Wedge High Tibial Osteotomy in the Medial Compartment
      Osteoarthritis of the Knee Joint: Comparison between the Aescula and TomoFix
      Plate.
AB  - BACKGROUND: The purpose of this study was to compare the results of Aescula and
      TomoFix plates used for biplanar open wedge high tibial osteotomy in medial
      osteoarthritis of the knee joint with varus deformity. METHODS: A consecutive
      series of 50 cases of biplanar open wedge high tibial osteotomy were evaluated
      retrospectively. Group A contained 25 cases treated by using the Aescula plate,
      and group T contained 25 cases treated by using the TomoFix plate. Full weight
      bearing was permitted at 6 weeks after surgery in group A and at 2 weeks in group
      T. Clinical evaluations were performed at the final follow-up by using
      postoperative knee scores and functional scores. Radiographic analysis included
      postoperative mechanical femur-tibia angle, change in posterior tibial slope
      angle, and complications related to implants. The mean follow-up periods were 30
      months in group A and 26 months in group T. RESULTS: The knee and functional
      scores were improved at the final follow-up in both groups (p < 0.05), but no
      differences were observed between the two groups (p > 0.05). An acceptable
      correction angle was obtained in 52% of group A and in 84% of group T (p =
      0.015). Change in posterior tibial slope angle was larger in group A than in
      group T (p < 0.001), showing better maintenance of posterior tibial slope in
      group T. In group A, there were 3 cases of screw loosening and 4 cases of delayed
      union. In addition, there were residual varus deformities in 7 cases (6 in group
      A and 1 in group T). CONCLUSIONS: This study shows that firm fixation using a
      TomoFix plate for open wedge high tibial osteotomy produces better radiologic
      results and a low complication rate than those of the Aescula spacer plate.

PMID- 26217465
TI  - A Novel Non-Invasive Adjuvant Biomechanical Treatment for Patients with Altered
      Rehabilitation after Total Knee Arthroplasty: Results of a Pilot Investigation.
AB  - BACKGROUND: Many factors contribute to suboptimal results after total knee
      arthroplasty (TKA) but little is known regarding the value of postsurgical
      rehabilitation after TKA. We examined the effects of an enhanced closed kinematic
      chain exercises program (AposTherapy) on gait patterns and clinical outcomes
      among patients with a lack of progress in their postsurgical rehabilitation.
      METHODS: Twenty-two patients were prospectively followed during the study. Gait
      spatiotemporal parameters were measured at the initial evaluation, after 15
      minutes of therapy, and after 3 months of therapy. The Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) and the short form (SF) 36
      health survey were completed by patients before treatment and after 3 months of
      treatment. RESULTS: The WOMAC and SF-36 scores improved significantly after 3
      months of treatment. Gait velocity, single limb support, and step length of the
      operated leg improved significantly even after a single 15 minutes treatment.
      Normal gait velocity was observed in 36% of patients after 3 months of treatment.
      CONCLUSIONS: A physiotherapy program that included enhanced closed kinematic
      chain biomechanical therapy was beneficial for patients who experienced a
      suboptimal rehabilitation course after TKA.

PMID- 26217466
TI  - The Survivorship and Clinical Results of Minimally Invasive Unicompartmental Knee
      Arthroplasty at 10-Year Follow-up.
AB  - BACKGROUND: In this study, we investigated the long-term clinical results and
      survival rate of minimally invasive unicompartmental knee arthroplasty (UKA) by
      collecting cases that had been implanted more than 10 years ago. METHODS: One
      hundred and twenty-eight patients (166 cases) who underwent Oxford phase 3 medial
      UKA using the minimally invasive surgery from January 2002 to December 2002 were
      selected. The mean age of the patients at the time of surgery was 61 years, and
      the duration of the follow-up was minimum 10 years. Clinical and radiographic
      assessments were performed using the Knee Society clinical rating system, and the
      survival analysis was done by the Kaplan-Meier method with 95% confidence
      interval (CI). RESULTS: The mean Knee Society knee and function scores improved
      significantly from 53.8 points (range, 25 to 70 points) and 56.1 points (range,
      35 to 80 points) preoperatively to 85.4 points (range, 58 to 100 points) and 80.5
      points (range, 50 to 100 points) at 10-year follow-up, respectively (p < 0.001).
      Failures following the UKA occurred in 16 cases (9.6%), and the mean time of the
      occurrence of the failure was 6.2 years after the surgery. The 10-year survival
      rate was 90.5% (95% CI, 85.9 to 95.0) when failure was defined as all the
      reoperations, whereas the 10-year survival rate was 93.4% (95% CI, 89.6 to 97.1)
      when the cases in which only revision total knee arthroplasty was defined as
      failure. CONCLUSIONS: The results of this study show outstanding functions of the
      knee joint and satisfactory 10-year survival rate after minimally invasive UKA.
      Therefore, minimally invasive UKA could be a useful method in the treatment of
      osteoarthritis in one compartment of knee joint.

PMID- 26217467
TI  - Transparency to Reduce Surgical Implant Waste.
AB  - BACKGROUND: Rising health care costs and emphasis on value have placed the onus
      of reducing healthcare costs on the surgeon. METHODS: Financial data from 3,973
      hip, knee, and shoulder arthroplasties performed at a physician owned orthopedic
      hospital was retrospectively reviewed over a two-year period. A wasted implant
      financial report was posted starting the second year of the study. Each surgeon's
      performance could be identified by his peers. RESULTS: After posting of the
      financial report, 1.11% of all hip and knee arthroplasty cases had a waste event
      compared to 1.50% during the control year. Shoulder arthroplasty waste events
      occurred twice as often than that observed in hip and knee arthroplasty during
      the study period. A decrease in waste events was observed but was not
      statistically significant (p = 0.30). CONCLUSIONS: Posting a non-blinded wasted
      implant data sheet was associated with a reduction in the number of wasted
      orthopedic surgical implants in this series, although the reduction was not
      statistically significant.

PMID- 26217468
TI  - A Randomized Controlled Study to Compare the Total and Hidden Blood Loss in
      Computer-Assisted Surgery and Conventional Surgical Technique of Total Knee
      Replacement.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is associated with considerable blood
      loss. Computer-assisted surgery (CAS) is different from conventional TKA as it
      avoids opening the intramedullary canal. Hence, CAS should be associated with
      less blood loss. METHODS: Fifty-seven patients were randomized into two groups of
      CAS and conventional TKA. In conventional group intramedullary femoral and
      extramedullary tibial jigs were used whereas in CAS group imageless navigation
      system was used. All surgeries were done under tourniquet. Total and hidden blood
      loss was calculated in both groups and compared. RESULTS: The mean total blood
      loss was 980 mL in conventional group and 970 mL in CAS group with median of
      1,067 mL (range, 59 to 1,791 mL) in conventional group and 863 mL (range, 111 to
      2,032 mL) in CAS group. There was no significant difference in total blood loss
      between the two groups (p = 0.811). We have found significant hidden blood loss
      in both techniques, which is 54.8% of the total loss in the conventional
      technique and 59.5% in the computer-assisted navigation technique. CONCLUSIONS:
      There is no significant difference in total and hidden blood loss in the TKA in
      CAS and conventional TKA. However, there is significant hidden blood loss in both
      techniques. There was no relation of tourniquet time with blood loss.

PMID- 26217469
TI  - Risk of Anterior Femoral Notching in Navigated Total Knee Arthroplasty.
AB  - BACKGROUND: We retrospectively investigated the prevalence of femoral anterior
      notching and risk factors after total knee arthroplasty (TKA) using an image-free
      navigation system. METHODS: We retrospectively reviewed 148 consecutive TKAs in
      130 patients beginning in July 2005. Seventy knees (62 patients) underwent
      conventional TKA, and 78 knees (68 patients) received navigated TKA. We
      investigated the prevalence of femoral anterior notching and measured notching
      depth by conventional and navigated TKA. Additionally, the navigated TKA group
      was categorized into two subgroups according to whether anterior femoral notching
      had occurred. The degree of preoperative varus deformity, femoral bowing, and
      mediolateral suitability of the size of the femoral component were determined by
      reviewing preoperative and postoperative radiographs. The resection angle on the
      sagittal plane and the angle of external rotation that was set by the navigation
      system were checked when resecting the distal femur. Clinical outcomes were
      compared using range of motion (ROM) and the Hospital for Special Surgery (HSS)
      and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAX) scores
      between the two groups. RESULTS: The prevalence of anterior femoral notching by
      conventional TKA was 5.7%, and that for navigated TKA was 16.7% (p = 0.037). Mean
      notching depth by conventional TKA was 2.92 +/- 1.18 mm (range, 1.8 to 4.5 mm)
      and 3.32 +/- 1.54 mm (range, 1.55 to 6.93 mm) by navigated TKA. Preoperative
      anterior femoral bowing was observed in 61.5% (p = 0.047) and both anterior and
      lateral femoral bowing in five cases in notching group during navigated TKA (p =
      0.021). Oversized femoral components were inserted in 53.8% of cases (p = 0.035).
      No differences in clinical outcomes for ROM or the HSS and WOMAX scores were
      observed between the groups. A periprosthetic fracture, which was considered a
      notching-related side effect, occurred in one case each in the conventional and
      navigated TKA groups. CONCLUSIONS: Surgeons should be aware of the risks
      associated with anterior femoral notching when using a navigation system for TKA.
      A modification of the femoral cut should be considered when remarkable femoral
      bowing is observed.

PMID- 26217470
TI  - Evaluation of the Accuracy and Precision of a Next Generation Computer-Assisted
      Surgical System.
AB  - BACKGROUND: Computer-assisted orthopaedic surgery (CAOS) improves accuracy and
      reduces outliers in total knee arthroplasty (TKA). However, during the evaluation
      of CAOS systems, the error generated by the guidance system (hardware and
      software) has been generally overlooked. Limited information is available on the
      accuracy and precision of specific CAOS systems with regard to intraoperative
      final resection measurements. The purpose of this study was to assess the
      accuracy and precision of a next generation CAOS system and investigate the
      impact of extra-articular deformity on the system-level errors generated during
      intraoperative resection measurement. METHODS: TKA surgeries were performed on
      twenty-eight artificial knee inserts with various types of extra-articular
      deformity (12 neutral, 12 varus, and 4 valgus). Surgical resection parameters
      (resection depths and alignment angles) were compared between postoperative three
      dimensional (3D) scan-based measurements and intraoperative CAOS measurements.
      Using the 3D scan-based measurements as control, the accuracy (mean error) and
      precision (associated standard deviation) of the CAOS system were assessed. The
      impact of extra-articular deformity on the CAOS system measurement errors was
      also investigated. RESULTS: The pooled mean unsigned errors generated by the CAOS
      system were equal or less than 0.61 mm and 0.64 degrees  for resection depths and
      alignment angles, respectively. No clinically meaningful biases were found in the
      measurements of resection depths (< 0.5 mm) and alignment angles (< 0.5 degrees
      ). Extra-articular deformity did not show significant effect on the measurement
      errors generated by the CAOS system investigated. CONCLUSIONS: This study
      presented a set of methodology and workflow to assess the system-level accuracy
      and precision of CAOS systems. The data demonstrated that the CAOS system
      investigated can offer accurate and precise intraoperative measurements of TKA
      resection parameters, regardless of the presence of extra-articular deformity in
      the knee.

PMID- 26217471
TI  - Gender Affects Early Postoperative Outcomes of Rotator Cuff Repair.
AB  - BACKGROUND: The literature does not provide consistent information on the impact
      of patients' gender on recovery after rotator cuff repair. The purpose of this
      study was to determine whether gender affects pain and functional recovery in the
      early postoperative period after rotator cuff repair. METHODS: Eighty patients
      (40 men and 40 women) were prospectively enrolled. Pain intensity and functional
      recovery were evaluated, using visual analog scale (VAS) pain score and range of
      motion on each of the first 5 postoperative days, at 2 and 6 weeks and at 3, 6,
      and 12 months after surgery. Perioperative medication-related adverse effects and
      postoperative complications were also assessed. RESULTS: The mean VAS pain score
      was significantly higher for women than men at 2 weeks after surgery (p = 0.035).
      For all other periods, there was no significant difference between men and women
      in VAS pain scores, although women had higher scores than men. Mean forward
      flexion in women was significantly lower than men at 6 weeks after surgery (p =
      0.033) and the mean degree of external rotation in women was significantly lower
      than men at 6 weeks (p = 0.007) and at 3 months (p = 0.017) after surgery. There
      was no significant difference in medication-related adverse effects or
      postoperative complications. CONCLUSIONS: Women had more pain and slower recovery
      of shoulder motion than men during the first 3 months after rotator cuff repair.
      These findings can serve as guidelines for pain management and rehabilitation
      after surgery and can help explain postoperative recovery patterns to patients
      with scheduled rotator cuff repair.

PMID- 26217472
TI  - Unstable Simple Elbow Dislocation Treated with the Repair of Lateral Collateral
      Ligament Complex.
AB  - BACKGROUND: Unstable simple elbow dislocation (USED) repair is challenged by the
      maintenance of joint reduction; hence, primary repair or reconstruction of
      disrupted ligaments is required to maintain the congruency and allow early motion
      of the elbow. We evaluated the effectiveness and the outcome of lateral
      collateral ligament (LCL) complex repair with additional medial collateral
      ligament (MCL) repair in cases of USED. METHODS: We retrospectively reviewed 21
      cases of diagnosed USED without fractures around the elbow that were treated with
      primary ligament repair. In all cases, anatomical repair of LCL complex with or
      without common extensor origin was performed using suture anchor and the bone
      tunnel method. Next, the instability and congruency of elbow for a full range of
      motion were evaluated under the image intensifier. MCL was repaired only if
      unstable or incongruent elbow was observed. Clinical outcomes were evaluated
      using the Mayo elbow performance score (MEPS) and radiographic outcomes on last
      follow-up images. RESULTS: All cases achieved a stable elbow on radiographic and
      clinical results. LCL complex repair alone was sufficient to obtain the stable
      elbow in 17 of 21 cases. Four cases required additional MCL repair after
      restoration of the LCL complex. The overall mean MEPS was 91 (range, 70 to 100):
      excellent in 12 cases, good in 7 cases, and fair in 2 cases. All 17 cases with
      LCL complex repair only and 2 of 4 cases with additional MCL repair had excellent
      or good results by MEPS. CONCLUSIONS: USED requires surgical treatment to achieve
      a congruent and stable joint. If the repair of lateral stabilizer such as LCL
      complex acquires enough joint stability to maintain a full range of motion, it
      may not be necessary to repair the medial stabilizer in all cases of USED.

PMID- 26217473
TI  - Bone Transport for Reconstruction in Benign Bone Tumors.
AB  - BACKGROUND: The aim of this study was to assess the results of using the Ilizarov
      apparatus to transport bones in the treatment of benign bone tumors. METHODS:
      Seven patients (six males and one female) with benign bone tumors were treated by
      bone transport with an Ilizarov apparatus at our institution. Their mean age at
      surgery was 14.4 years (range, 4.8 to 36.9 years). The histological diagnoses
      were osteofibrous dysplasia (4), giant-cell tumor (1), intraosseous cavernous
      hemangioma (1), and aneurysmal bone cyst (1). Three radiological indices were
      used for evaluating the results: an external fixation index, a distraction index,
      and a maturation index. The bone and functional results were evaluated according
      to the Association for the Study and Application of the Method of Ilizarov
      classification. RESULTS: Five patients had bone union at the reconstructed site,
      one patient had a local recurrence, and the other had a nonunion at the docking
      site. The mean length of distraction was 7.3 cm (range, 5.1 to 12.1 cm). The mean
      external fixation index was 26.0 day/cm (range, 19.8 to 32.5 day/cm), the
      distraction index was 9.6 day/cm (range, 6.8 to 12.0 day/cm), and the maturation
      index was 14.9 day/cm (range, 8.0 to 22.5 day/cm). Ultimately, the bone and the
      functional results were rated excellent in six cases and good in one case.
      CONCLUSIONS: Bone transport using the Ilizarov apparatus is a good treatment
      option in patients with bone defects after the resection of an active or
      aggressive benign bone tumor.

PMID- 26217474
TI  - Distinct Clinical Characteristics of Unplanned Excision in Synovial Sarcoma.
AB  - BACKGROUND: We aimed to describe the clinical characteristics and outcomes of
      unplanned excisions of synovial sarcomas. METHODS: In total, 90 patients with
      synovial sarcomas in the extremities were retrospectively reviewed. Patients were
      divided into unplanned excision (n = 38) and planned excision (n = 52) groups.
      The average follow-up period was 6 years. The clinicopathological characteristics
      and oncologic outcomes were compared. RESULTS: The unplanned excision group
      showed longer duration of symptoms before diagnosis (p = 0.023), smaller lesion
      dimensions (p = 0.001), superficial location (p = 0.049), and predilection in the
      upper extremities (p = 0.037). Synovial sarcomas were most commonly misdiagnosed
      as neurogenic tumors (56%) in the upper extremities or as cystic masses (47%) in
      the lower extremities. Oncological outcomes, including disease-specific survival,
      metastasis-free survival, or local recurrence were not significantly different
      between the 2 groups (p = 0.159, p = 0.444, and p = 0.335, respectively).
      Repeated unplanned excision (p = 0.012) and delayed re-excision (p = 0.038) were
      significant risk factors for local recurrence in the unplanned excision group.
      CONCLUSIONS: Synovial sarcomas treated with unplanned excision had distinct
      characteristics. These findings are important for developing diagnostic and
      therapeutic strategies for synovial sarcoma.

PMID- 26217475
TI  - Breakage of a Lag Screw of Cephalomedullary Nail: A Technique of Removal.
AB  - A broken lag screw of the cephalomedullary nail is a rare condition. Removal of
      the retained lag screw from the femoral head is also very challenging. This
      article describes a surgical technique and the modified instrument that was
      available in the operating room for removing the broken implant by closed
      technique. 

PMID- 26217476
TI  - Osteochondrolipoma Presenting as a Popliteal Cyst.
AB  - Here, we describe a popliteal mass that was initially misdiagnosed as a simple
      popliteal cyst, which finally turned out to be osteochondrolipoma. A 63-year-old
      housewife presented with sustained knee pain in association with a palpable mass
      on the popliteal fossa. The mass was in the posteromedial area and soft, non
      tender, non-movable in the posteromedial area. Using plain radiography, the mass
      appeared as a round, soft tissue density lesion containing bony fragments. We
      performed an ultrasound-guided needle biopsy in conjunction with magnetic
      resonance imaging, followed by an open excisional biopsy. Microscopically,
      histological sections showed a lipoma with cartilaginous and osseous
      differentiation, finally diagnosed as osteochondrolipoma. In conclusion,
      popliteal masses are not always simple cysts, and the evaluation of masses in the
      popliteal fossa is always necessary. 

PMID- 26217477
TI  - Pure Varus Injury to the Knee Joint.
AB  - A 30-year-old male was involved in a car accident. Radiographs revealed a
      depressed marginal fracture of the medial tibial plateau and an avulsion fracture
      of the fibular head. Magnetic resonance imaging showed avulsion fracture of
      Gerdy's tubercle, injury to the posterior cruciate ligament (PCL), posterior horn
      of the medial meniscus, and the attachments of the lateral collateral ligament
      and the biceps femoris tendon. The depressed fracture of the medial tibial
      plateau was elevated and stabilized using a cannulated screw and washer. The
      injured lateral and posterolateral corner (PLC) structures were repaired and
      augmented by PLC reconstruction. However, the avulsion fracture of Gerdy's
      tubercle was not fixed because it was minimally displaced and the torn PCL was
      also not repaired or reconstructed. We present a unique case of pure varus injury
      to the knee joint. This case contributes to our understanding of the mechanism of
      knee injury and provides insight regarding appropriate treatment plans for this
      type of injury. 

PMID- 26217478
TI  - Medical Student Debt: What Perspective Should We Take?
AB  - Since medical education is expensive, healthcare professional students in many
      countries must take out loans to pay for their studies. The resultant levels of
      debt have created concerns at both the beginning and the end of undergraduate
      education. How should medical educators respond to these concerns? If educators
      are to look at medical education from the perspective of their students who are
      most in need, then they should think about this. Educators should think about
      their response when current or prospective students ask them about mitigating the
      costs of medical education. This may include questions about working during
      undergraduate studies, the costs of living in different locations, and the
      availability of bursaries that offer financial aid to students. Medical students
      should be encouraged to "think like an investor" when making decisions related to
      their medical education. Senior medical educators should be well placed to advise
      them in this regard. 

PMID- 26217479
TI  - Effects of the 2008 Global Economic Crisis on National Health Indicators: Results
      from the Korean National Health and Nutrition Examination Survey.
AB  - BACKGROUND: The relationship between economics and health has been of great
      interest throughout the years. The accumulated data is not sufficient enough to
      carry out long-term studies from the viewpoint of morbidity, although Korea
      National Health and Nutrition Examination Survey (KNHANES) was carried out yearly
      since 1998 in Korea. Thus, we investigated the effect of the 2008 global economic
      crisis on health indicators of Korea. METHODS: Health indicators were selected by
      paired t-test based on 2007 and 2009 KNHANES data. Age, gender, body mass index
      (BMI), smoking, drinking, exercise, education, income, working status, and stress
      were used as confounding factors, which were analyzed with logistic and probit
      analyses. Validation was done by comparing gross domestic product (GDP) growth
      rates and probit analyses results of 2007-2012 KNHANES data. RESULTS: Among
      several health indicators, the prevalence of hypertension and stress perception
      was higher after the economic crisis. Factors related with higher hypertension
      prevalence include older age, male gender, higher BMI, no current tobacco use,
      recent drinking, lower education levels, and stress perception. Factors related
      with more stress perception were younger age, female gender, current smoking,
      lower education levels, and lower income. GDP growth rates, a macroeconomic
      indicator, are inversely associated with hypertension prevalence with a one-year
      lag, and also inversely associated with stress perception without time lag.
      CONCLUSION: The economic crisis increased the prevalence of hypertension and
      stress perception. In the case of GDP growth rate change, hypertension was an
      inversely lagging indicator and stress perception was an inversely-related
      coincident indicator.

PMID- 26217480
TI  - Measuring Low Density Lipoprotein Cholesterol: Comparison of Direct Measurement
      by HiSens Reagents and Friedewald Estimation.
AB  - BACKGROUND: Directly measured low density lipoprotein cholesterol (DLDLC) has
      been reported to be more accurate than calculated low density lipoprotein
      cholesterol (CLDLC) using the Friedewald equation. However, some limitations of
      DLDLC have been reported. In this study, we evaluated differences between CLDLC
      and DLDLC measured using HiSens reagents. METHODS: Data were collected from 582
      persons undergoing routine physical examinations at a general hospital. LDLC
      measurements were made directly or estimated using the Friedewald formula, and
      were classified according to the National Cholesterol Education Program's Adult
      Treatment Panel III guidelines. The relationship between these differences and
      other clinically relevant factors, such as triglyceride (TG) levels, were
      examined using multiple logistic regression analysis. RESULTS: The DLDLC and
      CLDLC were strongly correlated according to simple linear regression analysis
      (r=0.917, P<0.001) but the mean difference between measurements was -11.0+/-15.3
      (-62 to 90.5) mg/dL (P<0.001). For more than 10 mg/dL of their absolute
      differences, the DLDLC was typically lower than the CLDLC. The highest
      discrepancies in LDLC measurements occurred when LDLC was more than 160 mg/dL and
      less than 190 mg/dL. Differences in LDLC measurements were prone to striking
      negative and positive biases dependent on CLDLC and TG concentrations,
      respectively (all r>0.5). CONCLUSION: Unlike other studies, DLDLC was
      significantly lower than CLDLC and the large differences in LDLC concentrations
      were not dependent on TG concentration. Our work suggests that verification of
      DLDLC accuracy is needed and differences in LDLC measurements should be accounted
      for in making clinical decisions.

PMID- 26217481
TI  - The Intervening Role of Alexithymia in the Relationship between Attachment Styles
      and Test Anxiety among Gifted High School Students.
AB  - BACKGROUND: Given the importance of test anxiety among gifted students, the
      present study was conducted to assess the intervening role of alexithymia in the
      relationship between test anxiety and attachment styles. METHODS: By means of
      simple random sampling, 300 participants were selected out of all the students at
      two high schools in Khorramabad, which are affiliated with the Iranian National
      Organization for Development of Exceptional Talents (SAMPAD). Test anxiety,
      alexithymia, and attachment style questionnaires were used for data collection.
      Pearson correlation and path analysis tests were used to analyze the data.
      RESULTS: The results showed a positive relationship between test anxiety and
      avoidant and anxious attachment styles. Alexithymia and test anxiety were also
      positively related. Moreover, the results indicated that 12% of changes in test
      anxiety were explained by avoidant and anxious attachment styles as well as
      alexithymia. The relationship between the avoidant attachment style and test
      anxiety was 0.06 through alexithymia. However, no significant relationship
      between anxious attachment and test anxiety through alexithymia was found.
      CONCLUSION: The avoidant attachment style leads to test anxiety when the level of
      alexithymia increases in an individual.

PMID- 26217482
TI  - Non-Coronary Patients with Severe Chest Pain Show More Irrational Beliefs
      Compared to Patients with Mild Pain.
AB  - BACKGROUND: Despite providing insufficient medical evidence of the existence of a
      real cardiac condition, patients with non-coronary chest pain still interpret
      their pain incorrectly. The present study, therefore, sought to compare the
      irrational beliefs in non-coronary patients with mild chest pain against those
      with severe chest pain. METHODS: A cross-sectional design was used. The
      statistical population comprised non-coronary patients who presented to the Heart
      Emergency Center of Kermanshah city, Iran. Using a matching method, 96
      participants were selected and studied in two groups of 48. The instruments used
      were the Comorbidity Index, Brief Pain Index, and the Jones Irrational Beliefs
      Test (short-form). The multivariate analysis of variance, chi-square test, and t
      test were used for data analysis. RESULTS: Controlling for the effects of age and
      comorbid conditions, the severity of three types of irrational beliefs, including
      emotional irresponsibility (P<0.001), hopelessness changes (P<0.001), and problem
      avoiding (P=0.002) was higher among patients with severe chest pain (according to
      effect level). However, in terms of demand for approval, no difference was seen
      between the two groups (P=0.180). CONCLUSION: Non-coronary patients with severe
      chest pain showed a greater number of irrational beliefs in comparison to
      patients with mild pain. Irrational beliefs are common mental occurrences in
      patients with non-coronary chest pain, and they should be attended to by health
      professionals, especially in severe non-coronary chest pain. Further
      investigation to determine the association between irrational beliefs and non
      coronary chest pain is necessary.

PMID- 26217483
TI  - Association between Living Arrangements and Influenza Vaccination Rates among
      Elderly South Korean People: The Fifth Korea National Health and Nutrition
      Examination Survey (KNHANES V-2).
AB  - BACKGROUND: This study aimed to investigate the association between living
      arrangements and influenza vaccination among elderly South Korean subjects.
      METHODS: We used data from the fifth Korean National Health and Nutrition
      Examination Survey. Participants older than 65 years were included and
      categorized into 4 groups according to the type of living arrangement as follows:
      (1) living alone group; (2) living with a spouse group; (3) living with offspring
      (without spouse) group; and (4) living with other family members group. A total
      of 1,435 participants were included in this cross-sectional analysis. RESULTS: A
      lower vaccination rate was observed in the living with offspring (without spouse)
      group, whereas the living with a spouse group had higher rates of both seasonal
      and H1N1 influenza vaccination. After adjusting for age, sex, region, education
      level, income level, and number of comorbidities, the living with offspring
      (without spouse) group had a higher H1N1 vaccination non-receipt rate than the
      living alone group (odds ratio, 2.03; 95% confidence interval, 1.08-3.82).
      CONCLUSION: Influenza vaccination rates differed according to the type of living
      arrangement. Particularly, those living with offspring (without spouse) had the
      lowest H1N1 influenza vaccination rate compared to those with other living
      arrangements, and this difference was significant. Interventions to improve
      influenza vaccination coverage should target not only elderly persons who live
      alone, but also those living with offspring.

PMID- 26217484
TI  - Four Cases of Carbapenem-Resistant Enterobacteriaceae Infection from January to
      March in 2014.
AB  - Infection with carbapenem-resistant Enterobacteriaceae (CRE) and other multidrug
      resistant bacteria has increased rapidly in Korea. The Korea Centers for Disease
      Control and Prevention reported 1,609 cases of CRE infection in the country in
      2013. The risk factors for CRE infection include history of treatment with
      antibiotics such as cephalosporins or carbapenem, trauma, diabetes, cancer, and
      history of ventilator support. Herein, we report four cases of CRE infection seen
      during a 3-month period in our hospital in 2014. CRE infection is associated with
      a high mortality rate of 30% to 50%, even with combination antibiotic therapy.
      Prevention of CRE infection in hospital settings is fundamental to controlling
      its transmission. Key preventive measures include, contact precautions, hand
      hygiene, education of healthcare personnel, screening for CRE when indicated, and
      exercising discretion in prescribing carbapenem or cephalosporins. 

PMID- 26217485
TI  - Comments on Statistical Issues in July 2015.

PMID- 26217486
TI  - Technological, environmental and biological factors: referent variance values for
      infrared imaging of the bovine.
AB  - BACKGROUND: Despite its variety of potential applications, the wide
      implementation of infrared technology in cattle production faces technical,
      environmental and biological challenges similar to other indicators of metabolic
      state. Nine trials, divided into three classes (technological, environmental and
      biological factors) were conducted to illustrate the influence of these factors
      on body surface temperature assessed through infrared imaging. RESULTS:
      Evaluation of technological factors indicated the following: measurements of body
      temperatures were strongly repeatable when taken within 10 s; appropriateness of
      differing infrared camera technologies was influenced by distance to the target;
      and results were consistent when analysis of thermographs was compared between
      judges. Evaluation of environmental factors illustrated that wind and debris
      caused decreases in body surface temperatures without affecting metabolic rate;
      additionally, body surface temperature increased due to sunlight but returned to
      baseline values within minutes of shade exposure.
      Examination/investigation/exploration of animal factors demonstrated that
      exercise caused an increase in body surface temperature and metabolic rate.
      Administration of sedative and anti-sedative caused changes on body surface
      temperature and metabolic rate, and during late pregnancy a foetal thermal
      imprint was visible through abdominal infrared imaging. CONCLUSION: The above
      factors should be considered in order to standardize operational procedures for
      taking thermographs, thereby optimizing the use of such technology in cattle
      operations.

PMID- 26217487
TI  - Amplicon sequencing for the quantification of spoilage microbiota in complex
      foods including bacterial spores.
AB  - BACKGROUND: Spoilage of food products is frequently caused by bacterial spores
      and lactic acid bacteria. Identification of these organisms by classic
      cultivation methods is limited by their ability to form colonies on nutrient agar
      plates. In this study, we adapted and optimized 16S rRNA amplicon sequencing for
      quantification of bacterial spores in a canned food matrix and for monitoring the
      outgrowth of spoilage microbiota in a ready-to-eat food matrix. RESULTS: The
      detection limit of bar-coded 16S rRNA amplicon sequencing was determined for the
      number of bacterial spores in a canned food matrix. Analysis of samples from a
      canned food matrix spiked with a mixture of equinumerous spores from the
      thermophiles, Geobacillus stearothermophilus and Geobacillus thermoglucosidans,
      and the mesophiles, Bacillus sporothermodurans, Bacillus cereus, and Bacillus
      subtilis, led to the detection of these spores with an average limit of 2 * 10(2)
      spores ml(-1). The data were normalized by setting the number of sequences
      resulting from DNA of an inactivated bacterial species, present in the matrix at
      the same concentration in all samples, to a fixed value for quantitative sample
      to-sample comparisons. The 16S rRNA amplicon sequencing method was also employed
      to monitor population dynamics in a ready-to-eat rice meal, incubated over a
      period of 12 days at 7  degrees C. The most predominant outgrowth was observed by
      the genera Leuconostoc, Bacillus, and Paenibacillus. Analysis of meals pre
      treated with weak acids showed inhibition of outgrowth of these three genera. The
      specificity of the amplicon synthesis was improved by the design of
      oligonucleotides that minimize the amplification of 16S rRNA genes from
      chloroplasts originating from plant-based material present in the food.
      CONCLUSION: This study shows that the composition of complex spoilage
      populations, including bacterial spores, can be monitored in complex food
      matrices by bar-coded amplicon sequencing in a quantitative manner. In order to
      allow sample-to-sample comparisons, normalizations based on background DNA are
      described. This method offers a solution for the identification and
      quantification of spoilage microbiota, which cannot be cultivated under standard
      laboratory conditions. The study indicates variable detection limits among
      species of bacterial spores resulting from differences in DNA extraction
      efficiencies.

PMID- 26217488
TI  - Prevalence of intestinal opportunistic parasites infections in the University
      hospital of Bobo-Dioulasso, Burkina Faso.
AB  - BACKGROUND: Gastrointestinal parasites infections are widespread in Africa and
      their prevalence infections vary from country to country. This study aimed at
      assessing the prevalence of opportunistic intestinal parasites infection and
      other gastrointestinal parasites infection among patients attending the
      laboratory of Parasitology and Mycology of the University Hospital Souro Sanou of
      Bobo-Dioulasso. METHODS: A hospital cross-sectional based study was conducted
      from April to August, 2012. Participants were persons whom parasitological
      examination of stools has been prescribed by a clinician. The stools examination
      methods included direct wet saline examination, lugol's iodine staining
      technique, formol-ether concentration and modified Ziehl-Neelsen staining. We
      recorded age and sex information for each patient. RESULTS: The overall
      prevalence of intestinal parasite infections was 65.3 % (190/291). Majority of
      the parasitic infections was waterborne (64.3 %) consisting of high prevalence of
      Cryptosporidium sp. (26.5 %) and Entamoeba histolytica/dispar (23.4 %). The
      prevalence of opportunistic parasites was 28.9 % and Cryptosporidium sp. was the
      most prevalent species followed by Blastocystis sp. (1.0 %), Cyclospora sp. (0.7
      %) and Isospora belli (0.7 %). The prevalence of intestinal helminthes was 1.7 %.
      CONCLUSIONS: The prevalence of intestinal parasitism in general remains high in
      Bobo-Dioulasso requiring the establishment of adequate diagnostic techniques,
      treatment and prevention.

PMID- 26217489
TI  - Removal of inorganic mercury from aquatic environments by multi-walled carbon
      nanotubes.
AB  - BACKGROUND: Mercury is considered as a toxic heavy metal in aquatic environments
      due to accumulation in bodies of living organisms. Exposure to mercury may lead
      to different toxic effects in humans including damages to kidneys and nervous
      system. MATERIALS AND METHODS: Multi-walled carbon nanotubes (MWCNTs) were
      selected as sorbent to remove mercury from aqueous solution using batch
      technique. ICP instrument was used to determine the amount of mercury in
      solution. Moreover, pH, contact time and initial concentration of mercury were
      studied to determine the influence of these parameters on the adsorption
      conditions. RESULTS: Results indicate that the adsorption strongly depended on pH
      and the best pH for adsorption is about 7. The rate of adsorption process
      initially was rapid but it was gradually reduced with increasing of contact time
      and reached the equilibrium after 120 min. In addition, more than 85 % of initial
      concentration of 0.1 mg/l was removed at 0.5 g/l concentration of sorbent and
      contact time of 120 min. Meanwhile, the adsorption process followed the pseudo
      second-order model and the adsorption isotherms could be described by both the
      Freundlich and the Langmuir models. CONCLUSION: This study showed that MWCNTs can
      effectively remove inorganic mercury from aqueous solutions as adsorbent.

PMID- 26217491
TI  - Corrigendum: Proteomic analysis of colon and rectal carcinoma using standard and
      customized databases.

PMID- 26217490
TI  - Impacts of elevated atmospheric CO2 on nutrient content of important food crops.
AB  - One of the many ways that climate change may affect human health is by altering
      the nutrient content of food crops. However, previous attempts to study the
      effects of increased atmospheric CO2 on crop nutrition have been limited by small
      sample sizes and/or artificial growing conditions. Here we present data from a
      meta-analysis of the nutritional contents of the edible portions of 41 cultivars
      of six major crop species grown using free-air CO2 enrichment (FACE) technology
      to expose crops to ambient and elevated CO2 concentrations in otherwise normal
      field cultivation conditions. This data, collected across three continents,
      represents over ten times more data on the nutrient content of crops grown in
      FACE experiments than was previously available. We expect it to be deeply useful
      to future studies, such as efforts to understand the impacts of elevated
      atmospheric CO2 on crop macro- and micronutrient concentrations, or attempts to
      alleviate harmful effects of these changes for the billions of people who depend
      on these crops for essential nutrients. 

PMID- 26217492
TI  - The relationship of individual comorbid chronic conditions to diabetes care
      quality.
AB  - OBJECTIVE: Multimorbidity affects 26 million persons with diabetes, and care for
      comorbid chronic conditions may impact diabetes care quality. The aim of this
      study was to determine which chronic conditions were related to lack of
      achievement or achievement of diabetes care quality goals to determine potential
      targets for future interventions. RESEARCH DESIGN AND METHODS: This is an
      exploratory retrospective analysis of electronic health record data for 23 430
      adults, aged 18-75, with diabetes who were seen at seven Midwestern US health
      systems. The main outcome measures were achievement of six diabetes quality
      metrics in the reporting year, 2011 (glycated haemoglobin (HbA1c) control and
      testing, low-density lipoprotein control and testing, blood pressure control,
      kidney testing). Explanatory variables were 62 chronic condition indicators.
      Analyses were adjusted for baseline patient sociodemographic and healthcare
      utilization factors. RESULTS: The 62 chronic conditions varied in their
      relationships to diabetes care goal achievement for specific care goals.
      Congestive heart failure was related to lack of achievement of cholesterol
      management goals. Obesity was related to lack of HbA1c and BP control. Mental
      health conditions were related to both lack of achievement and achievement of
      different care goals. Three conditions were related to lack of cholesterol
      testing, including congestive heart failure and substance-use disorders. Of 17
      conditions related to achieving control goals, 16 were related to achieving HbA1c
      control. One-half of the comorbid conditions did not predict diabetes care
      quality. CONCLUSIONS: Future interventions could target patients at risk for not
      achieving diabetes care for specific care goals based on their individual
      comorbidities.

PMID- 26217493
TI  - Clinical characteristics, complications, comorbidities and treatment patterns
      among patients with type 2 diabetes mellitus in a large integrated health system.
AB  - PURPOSE: To compare the prevalence of diabetes-related complications and
      comorbidities, clinical characteristics, glycemic control, and treatment patterns
      in patients with type 2 diabetes (T2D) within a large integrated healthcare
      system in 2008 vs 2013. METHODS: An electronic health record system was used to
      create a cross-sectional summary of all patients with T2D as on 1 July 2008 and 1
      July 2013. Differences between the two data sets were assessed after adjusting
      for age, gender, race, and household income. RESULTS: In 2008 and 2013, 24 493
      and 41 582 patients with T2D were identified, respectively, of which the majority
      were male (52.3% and 50.1%) and Caucasian (79% and 75.2%). The mean ages (years)
      were 64.8 and 64.3. The percentages of patients across the defined A1C categories
      were 64.3 and 66.7 for <7%, 21.1 and 18.8 for 7-7.9%, 7.8 and 7.5 for 8-8.9%, and
      6.8 and 7.0 for >=9% in 2008 and 2013, respectively. The most prevalent T2D
      related comorbidities were hypertension (82.5% and 87.2%) and cardiovascular
      disease (26.9% and 22.3%) in 2008 and 2013, respectively. Thiazolidinedione and
      sulfonylurea use decreased, whereas metformin and dipeptidyl peptidase-4
      inhibitor use increased in the 5-year period. CONCLUSIONS: Patients with T2D are
      characterized by a high number of comorbidities. Over 85% of the patients had an
      A1C<8% within our integrated health delivery system in 2008 and 2013. In 2008 and
      2013, metformin therapy was the most commonly utilized antidiabetic agent, and
      sulfonylureas were the most commonly utilized oral antidiabetic agent in
      combination with metformin. As integrated health systems assume greater shared
      financial risk in newer payment models, achieving glycemic targets (A1C) and the
      management of comorbidities will become ever-more important, for preventing
      diabetes-related complications, as well as to ensure reimbursement for the
      medical care that is rendered to patients with diabetes.

PMID- 26217494
TI  - BMC Obesity - expanding the BMC series into an important area of research.
AB  - This Editorial marks the launch of an important new journal to join the BMC
      series portfolio - BMC Obesity. BMC Obesity joins BMC Cancer as the second
      journal within the series to focus on a particular condition in the human body
      and the factors that contribute towards it. 

PMID- 26217495
TI  - Dutch General Practitioners' weight management policy for overweight and obese
      patients.
AB  - BACKGROUND: General practitioners (GPs) can play an important role in both the
      prevention and management of overweight and obesity. Current general practice
      guidelines in the Netherlands allow room for GPs to execute their own weight
      management policy. OBJECTIVE: To examine GPs' current weight management policy
      and the factors associated with this policy. METHODS: 800 Dutch GPs were asked to
      complete a questionnaire in December 2012. The questionnaire items were based on
      the Dutch Obesity Standard for GPs. The data were analyzed by means of
      descriptive statistics and multiple linear regression analyses in 2013. RESULTS:
      In total, 307 GPs (39.0%) responded. Most respondents (82.9%) considered weight
      management as part of their responsibility for providing care. GPs aged <48 years
      discussed weight less frequent. Next, weight is less frequently discussed with
      patients without weight-related comorbidities or with moderately overweight
      patients compared to obese patients. On average, 47.7% of the GPs reported to
      refer obese patients to a weight management professional, preferably a dietitian
      (98.3%). GPs with a BMI >= 25 kg/m(2) were less likely to refer obese patients.
      In addition, GPs who had frequent contact with a dietitian were more likely to
      refer obese patients. CONCLUSIONS: In the context of General Practice and
      preventive medicine, GPs' discussion of weight and the variety of obesity
      determinants with their moderately overweight patients deserves more attention,
      especially from younger GPs. Strengthening interdisciplinary collaboration
      between GPs and dietitians could increase the referral percentage for dietary
      treatment.

PMID- 26217496
TI  - An interview with Philip McTernan, section editor for the basic science section.
AB  - Philip McTernan is a Reader Associate Professor within Warwick Medical School at
      the University of Warwick. His main interests involve understanding the causes
      and underlying mechanisms of obesity mediated type 2 diabetes and investigating
      potential therapeutic targets. He is currently researching the origins of
      inflammation in human adipocytes and is the Section Editor for the new 'Basic
      Science' section in BMC Obesity. In this interview we find out a little more
      about the key issues in this area of obesity research. 

PMID- 26217497
TI  - Design of CIAO, a research program to support the development of an integrated
      approach to prevent overweight and obesity in the Netherlands.
AB  - BACKGROUND: The aim of this paper is to describe the research aims, concepts and
      methods of the research Consortium Integrated Approach of Overweight (CIAO). CIAO
      is a concerted action of five Academic Collaborative Centres, local
      collaborations between academic institutions, regional public health services,
      local authorities and other relevant sectors in the Netherlands. Prior research
      revealed lacunas in knowledge of and skills related to five elements of the
      integrated approach of overweight prevention in children (based upon the French
      EPODE approach), namely political support, parental education, implementation,
      social marketing and evaluation. CIAO aims to gain theoretical and practical
      insight of these elements through five sub-studies and to develop, based on these
      data, a framework for monitoring and evaluation. METHODS/DESIGN: For this
      research program, mixed methods are used in all the five sub-studies. First,
      problem specification through literature research and consultation of
      stakeholders, experts, health promotion specialists, parents and policy makers
      will be carried out. Based on this information, models, theoretical frameworks
      and practical instruments will be developed, tested and evaluated in the
      communities that implement the integrated approach to prevent overweight in
      children. Knowledge obtained from these studies and insights from experts and
      stakeholders will be combined to create an evaluation framework to evaluate the
      integrated approach at central, local and individual levels that will be
      applicable to daily practice. DISCUSSION: This innovative research program
      stimulates sub-studies to collaborate with local stakeholders and to share and
      integrate their knowledge, methodology and results. Therefore, the output of this
      program (both knowledge and practical tools) will be matched and form building
      blocks of a blueprint for a local evidence- and practice-based integrated
      approach towards prevention of overweight in children. The output will then
      support various communities to further optimize the implementation and
      subsequently the effects of this approach.

PMID- 26217498
TI  - Inhalation of carbon monoxide is ineffective as a long-term therapy to reduce
      obesity in mice fed a high fat diet.
AB  - BACKGROUND: Previous studies have demonstrated that induction of heme oxygenase-1
      results in weight loss in several rodent models of obesity. However, the specific
      role of the heme oxygenase-1 metabolite, carbon monoxide (CO), in this response
      has yet to be established. We recently reported that chronic treatment with CO
      releasing molecules results in prevention of weight gain in mice fed a high fat
      diet. In the present study, we sought to determine the effect of chronic CO
      inhalation on the development and reversal of high fat diet induced obesity.
      RESULTS: CO inhalation at both levels initially resulted in a prevention and
      reversal of body weight and fat mass over the first 10 weeks of treatment,
      however, this effect was not sustained. CO inhalation in the prevention groups
      also had an early effect to lower fasting blood glucose but this effect also was
      not sustained. CONCLUSIONS: Our results demonstrate that CO inhalation has a
      transient effect to prevent and reduce body weight which is not sustained
      chronically in mice fed a high fat diet. These results suggest that chronic CO
      inhalation therapy is not an effective treatment to induce long term weight loss.

PMID- 26217499
TI  - Obesity and overweight: prevalence and associated socio demographic factors among
      mothers in three different areas in the Gaza Strip-Palestine: a cross-sectional
      study.
AB  - BACKGROUND: The increasing number of obesity and overweight cases in developing
      countries, especially among women, requires serious attention because of its
      effects on the health care system and the quality of life. Few studies have been
      conducted in the Gaza Strip to determine obesity and overweight prevalence and
      the associated factors. This study aimed at determining the prevalence of obesity
      and overweight cases in relation to socio-demographic factors among mothers aged
      18-50 years in the Gaza Strip-Palestine from June 2012 to September 2012. Mothers
      childbearing age 18-50 years (n = 357) were selected using a cross-sectional
      multistage sampling methodology from three different geographical locations,
      namely, El Remal urban area, Jabalia refugee camp, and Al Qarrara rural area. The
      weight and height of the mothers were measured, and their body mass indexes (BMI)
      were computed. The mothers were categorized according to the criteria of World
      Health Organization (WHO) for BMI. The criteria categorize mothers as overweight
      if they have a BMI 25-29.9 kg/m(2) and obese if their BMI >= 30.0 kg/m(2).
      RESULTS: Obesity and overweight rates in urban area, refugee camp, and rural area
      were found to be 57.0%, 66.8%, and 67.5%, respectively. Moreover, BMI increased
      with age, adjusted b = 0.39; 95% CI (0.31, 0.48); p = < 0.001, whereas BMI was
      lower in low-income subjects, adjusted b = -1.59, 95% CI (-2.74,-0.44), p =
      0.007. Housewives were more susceptible to obesity than employed woman, adjusted
      b = -2.76, 95% CI (-5.33,-0.19), p = 0.036. However, the study found no
      association among BMI level and household size, geographical location,
      educational level, and family assistance. CONCLUSIONS: The results showed that
      obesity and being overweight are highly prevalent among women in the Gaza Strip.
      Independent predictors of obesity in the population studied were increasing age,
      high income, and housewives. This finding is an important baseline for the
      monitoring of obesity and overweight cases in the future and highlights the need
      for community-based programs to combat this problem in Palestine.

PMID- 26217500
TI  - Case management via telephone counseling and SMS for weight maintenance in
      adolescent obesity: study concept of the TeAM program.
AB  - BACKGROUND: In-patient obesity treatment programs for adolescents are associated
      with good success and substantial weight loss. However, maintaining weight loss
      remains a challenge. This article presents the concept of the TeAM (Telephone
      counseling as Adiposity Management) program. TeAM is an innovative, weight
      maintenance program for obese adolescents after in-patient therapy. It applies
      the case management approach in combination with new media (telephone counseling,
      web forum, and SMS messaging). Adolescents (14-18 years) were recruited via
      German rehabilitation hospitals. The intervention of the TeAM program consists of
      telephone counseling through trained case managers in order to maintain body
      weight reduction (expressed as BMI-SDS: body mass index standard deviation score)
      achieved during an in-patient obesity therapy. At baseline and after completion
      of the program, participants provide anthropometric measures (obtained by trained
      medical staff) as well as information on socio-demographics, usage of health
      services, psychosocial status, daily physical activity, media consumption, and
      eating behavior. The core of the intervention is regular telephone contact with
      the adolescent participants combined with tailored SMS messages. Telephone
      counseling is based on the systemic approach and addresses the topics of mental
      hygiene, physical activity, sedentary behavior, diet and eating behavior.
      RESULTS: Baseline data of the feasibility study: Thirty-eight adolescents were
      recruited for the feasibility study (14 male, 24 female; mean age 15.82 years);
      out of them, ten participants lived with a single parent; 68% planned to graduate
      from school without pre-requisites for university admission (O-level). The mean
      weight loss during in-patient treatment was 0.32 BMI-SDS units. Mean BMI at the
      start of intervention was 31.93 kg/m(2), corresponding to a mean BMI-SDS of 2.48.
      CONCLUSIONS: Weight maintenance treatment programs for adolescent obesity
      utilizing new media are a promising approach as they reach adolescents directly
      within their everyday life. TRIAL REGISTRATION: DRKS00004583.

PMID- 26217501
TI  - Body mass index and measures of body fat for defining obesity and underweight: a
      cross-sectional, population-based study.
AB  - BACKGROUND: The body mass index (BMI) is commonly used as a surrogate marker for
      adiposity. However, the BMI indicates weight-for-height without considering
      differences in body composition and the contribution of body fat to overall body
      weight. The aim of this cross-sectional study was to identify sex-and-age
      specific values for percentage body fat (%BF), measured using whole body dual
      energy x-ray absorptiometry (DXA), that correspond to BMI 18.5 kg/m(2) (threshold
      for underweight), 25.0 kg/m(2) (overweight) and 30.0 kg/m(2) (obesity) and
      compare the prevalence of underweight, overweight and obesity in the adult white
      Australian population using these BMI thresholds and equivalent values for %BF.
      These analyses utilise data from randomly-selected men (n = 1446) and women (n =
      1045), age 20-96 years, who had concurrent anthropometry and DXA assessments as
      part of the Geelong Osteoporosis Study, 2001-2008. RESULTS: Values for %BF cut
      points for underweight, overweight and obesity were predicted from sex, age and
      BMI. Using these cut-points, the age-standardised prevalence among men for
      underweight was 3.1% (95% CI 2.1, 4.1), overweight 40.4% (95% CI 37.7, 43.1) and
      obesity 24.7% (95% CI 22.2, 27.1); among women, prevalence for underweight was
      3.8% (95% CI 2.6, 5.0), overweight 32.3% (95% CI 29.5, 35.2) and obesity 29.5%
      (95% CI 26.7, 32.3). Prevalence estimates using BMI criteria for men were:
      underweight 0.6% (95% CI 0.2, 1.1), overweight 45.5% (95% CI 42.7, 48.2) and
      obesity 19.7% (95% CI 17.5, 21.9); and for women, underweight 1.4% (95% CI 0.7,
      2.0), overweight 30.3% (95% CI 27.5, 33.1) and obesity 28.2% (95% CI 25.4, 31.0).
      CONCLUSIONS: Utilising a single BMI threshold may underestimate the true extent
      of obesity in the white population, particularly among men. Similarly, the BMI
      underestimates the prevalence of underweight, suggesting that this body build is
      apparent in the population, albeit at a low prevalence. Optimal thresholds for
      defining underweight and obesity will ultimately depend on risk assessment for
      impaired health and early mortality.

PMID- 26217502
TI  - Feasibility, acceptability and potential effectiveness of a mobile health
      (mHealth) weight management programme for New Zealand adults.
AB  - BACKGROUND: Mobile health (mHealth) behaviour change programmes use mobile phones
      and the internet to deliver health information and behaviour change support to
      participants. Such programmes offer a potentially cost-effective way to reach
      many individuals who do not currently access weight loss services. We developed a
      mHealth weight management programme using proven face-to-face behaviour change
      techniques and incorporating target population input. Our aim was to evaluate the
      feasibility, acceptability and potential effectiveness of this programme for
      ethnically diverse adults with a view to informing a larger trial. RESULTS: Fifty
      three adults who had a BMI of >=25 kg/m(2) and wanted to lose weight (81% female,
      mean age 42 years, mean BMI 35.7 kg/m(2), 26% Maori, 34% Pacific) received the
      eight-week mHealth weight loss programme. Anthropometric measures were taken at
      two face-to-face assessments at baseline and 12-weeks (i.e. four weeks after
      cessation of intervention). Twelve-week follow-up measurements were available for
      36/53 participants (68%). Non-completers were younger and more likely to be male
      and of Pacific ethnicity. Thirty five participants (66%) reported reading 'all or
      most' text messages sent and 96% responded to at least one text data collection
      question over the eight-week active intervention period. Eighty one per cent of
      participants logged in to the study website at least once during the eight-week
      study period. In the intention-to-treat analysis, mean weight change was -1.0 kg
      (SD 3.1) at 12 weeks (p = 0.024) and change in BMI was -0.34 kg/m(2) (SD 1.1) (p
      = 0.026). In the completers only analysis (n = 36), mean weight change was -1.4
      kg (SD 3.6) (p = 0.023) and change in BMI was -0.50 kg/m(2) (SD 1.3) (p = 0.025).
      CONCLUSIONS: A mHealth weight management programme is feasible to deliver to an
      ethnically diverse population. Changes in body weight and BMI at 12 weeks
      indicate that the programme could be effective in supporting people with weight
      loss. However, the high dropout rate indicates a need for further improvements to
      the programme. TRIAL REGISTRATION: ACTRN12612000850875.

PMID- 26217503
TI  - Moderate intensity physical activity prevents increased blood glucose
      concentrations, fat pad deposition and cardiac action potential prolongation
      following diet-induced obesity in a juvenile-adolescent rat model.
AB  - BACKGROUND: Both obesity and a lack of physical activity have been associated
      with an elevated risk of cardiovascular disease (CVD). The incidence of obesity
      is increasing, especially in juvenile-adolescents. While there is limited
      research examining the chronic effects of obesity in adolescent humans and animal
      models of this condition, little is also known concerning how moderate physical
      activity might prevent or attenuate secondary cardiovascular complications
      induced by obesity during adolescence. We investigated the effects of diet
      induced obesity (consisting of a high-fat, high-carbohydrate diet (HFHC)) on
      biometric indices, vascular and airway function, cardiovascular function,
      systemic oxidative stress and markers of inflammation in a juvenile-adolescent
      rodent model. Four groups were used: control (CON), physical activity (PA)
      treated, HFHC and HFHC + PA (n = 16 per group). HFHC feeding started at 4 weeks
      of age for a period of 12 weeks. Physical activity treatment was initiated (PA
      and HFHC + PA groups) when the animals were 8 weeks of age, for 8 weeks. RESULTS:
      Physical activity in juvenile-adolescent healthy rats showed no change in
      comparison to the CON group in all experimental parameters except for increases
      in lipid peroxidation, decreases in inflammatory cytokines, improvements in
      vascular reactivity and decreased atrial responses to positive chronotropic
      agents. The HFHC animals were mildly hyperglycemic, hypertensive, displayed renal
      hypertrophy and showed increased retroperitoneal fat pad deposition compared to
      the CON group. HFHC + PA rats were also hypertensive, however showed improvements
      in cardiac electrophysiology, body weight, fat pad deposition and inflammatory
      signaling, in comparison to the HFHC fed rats and CON animals. CONCLUSION: In
      conclusion, in a juvenile-adolescent animal model of diet-induced obesity
      engagement in physical activity is beneficial in reducing the inflammatory
      effects of obesity.

PMID- 26217504
TI  - Age- and sex-specific effects on weight loss outcomes in a comparison of sleeve
      gastrectomy and Roux-en-Y gastric bypass: a retrospective cohort study.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) are the
      most common bariatric procedures undertaken globally but there are no evidenced
      based criteria that inform the selection of one operation over the other. The
      purpose of this study was thus to compare weight loss outcomes between RYGBP and
      SG, and to define patient factors affecting weight loss. METHODS: A single-centre
      two-year follow-up retrospective cohort study of all adults who underwent either
      RYGBP (n = 422) or SG (n = 432) between 2007 and 2012, at University College
      London Hospitals National Health Service Foundation Trust, an academic tertiary
      referral centre, was undertaken. Multilevel linear regression was used to compare
      weight loss between groups, enabling adjustment for preoperative BMI (body mass
      index) and evaluation for interaction factors. RESULTS: One- and two-year results
      showed that unadjusted BMI loss was similar between groups; 13.7 kg/m(2) (95% CI:
      12.9, 14.6 kg/m(2)) and 12.8 kg/m(2) (95% CI: 11.8, 13.9 kg/m(2)) for RYGBP
      patients respectively compared with 13.3 kg/m(2) (95% CI: 12.0, 14.6 kg/m(2)) and
      11.5 kg/m(2) (95% CI: 10.1, 13.0 kg/m(2)) for SG patients respectively. Adjusting
      for preoperative BMI, there was 2.2 kg/m(2) (95% CI: 1.5, 2.8) and 2.3 kg/m(2)
      (95% CI: 1.3, 3.3) greater BMI loss in the RYGBP group compared to the SG group
      at one and two years respectively (P < 0.001 for both). The interaction analyses
      demonstrated that age and sex had important differential impacts on SG and RYGBP
      weight outcomes. Men under 40 and women over 50 years obtained on average far
      less benefit from SG compared to RYGBP, whereas men over 40 years and women under
      50 years experienced similar weight loss with either procedure (P = 0.001 and
      0.022 for interaction effects at one and two years respectively). CONCLUSIONS:
      Our results show that patient sex and age significantly impact on weight loss in
      a procedure-dependent manner and should be considered when choosing between RYGBP
      and SG. Optimizing procedure selection could enhance the effectiveness of
      bariatric surgery, thus further increasing the benefit-to-risk ratio of this
      highly effective intervention.

PMID- 26217505
TI  - The association of smoking and demographic characteristics on body mass index and
      obesity among adults in the U.S., 1999-2012.
AB  - BACKGROUND: The National Health and Nutrition Examination Surveys (NHANES) are an
      exceptional data source for studies of smoking and body weight because they are
      the only federal survey series collecting relevant information through detailed
      interviews and medical examinations. The associations of smoking status and
      demographic factors with body weight have not been evaluated fully in recent
      NHANES. METHODS: Using NHANES datasets from 1999 to 2012, this study uses
      ordinary-least squares and ordered probit models to investigate the association
      of smoking and selected demographic variables with body mass index (BMI) and the
      probability of being in BMI categories among adults aged 25-64 years, and it uses
      quantile regression to examine whether these factors affect individuals
      differently depending on where they are located across the BMI distribution.
      RESULTS: The sample consisted of 11,123 men and 10,949 women. Current smokers had
      significantly lower BMI than never smokers (1.97 unit for men and 1.46 unit for
      women), and there was modest variation across the BMI distribution. Among former
      smokers, only women had a slightly higher BMI compared to never smokers (0.46
      unit). Both men and women current smokers were more likely to be underweight and
      normal weight compared to never smokers and were less likely to be obese. Among
      men a one-year age increase elevated BMI by 0.2 unit throughout the BMI
      distribution, while for women an extra year of age increased BMI at the upper
      tail of the distribution more than at the lower tail. Education beyond high
      school was associated with a significant decrease in BMI among women, but much
      less so among men. Married men had higher BMI, but married women had
      significantly lower BMI, and this difference became larger at the upper tail.
      CONCLUSIONS: Compared to never smokers, men and women current smokers had lower
      BMI and lower probability of obesity, while only women former smokers had
      elevated BMIs and increased probability of obesity. In addition, we found that
      age, education and marital status were associated with different effects on BMI
      in men and women.

PMID- 26217506
TI  - Impact of an integrated obesity management system on patient's care - research
      protocol.
AB  - BACKGROUND: The majority of obese subjects are treated by primary care physicians
      (PCPs) who often feel uncomfortable with the management of obesity. In a previous
      study, we successfully developed, implemented and evaluated an obesity management
      system based on training and coaching of health professionals of family medicine
      groups (FMGs) by a team of experts in obesity management. Using a pre/post
      design, this study suggested a positive impact on health professionals'
      perceptions and reported obesity care. The current research project is aimed at
      evaluating the impact on obesity screening and care of this integrated obesity
      management system. We hypothesize that our program combining preceptorships with
      a virtual community and on-site coaching will improve: (1) management and weight
      loss of obese/overweight subjects treated by PCPs for hypertension, type 2
      diabetes or impaired glucose tolerance; and (2) screening and initial management
      of obesity among a regular follow-up group of patients of PCPs who practice in
      FMGs. METHODS/DESIGN: Ten FMGs will be approached for a practice monitoring
      project and will be randomised to receive the intervention developed in our
      previous project or will only be provided clinical practice guidelines. In the
      participating FMGs, we will enrol 22 patients per FMG with weight related
      targeted disease and 24 patients with regular follow-up. These patients will be
      evaluated for the care they received regarding screening and/or management of
      obesity using medical chart reviews, and will fill out a questionnaire on their
      lifestyle and satisfaction. They will also be examined for anthropometric
      measures, vital signs, blood markers for chronic diseases and physical fitness.
      The same patients will be assessed again after 18 months. The impact of the
      program on health professionals will be evaluated at baseline, and at 1 year.
      Qualitative data will also be collected from both professional and patient
      participants. Direct and indirect costs and QALYs will be evaluated as indicators
      of cost-effectiveness. DISCUSSION: In the context of the dramatic increase in
      obesity prevalence and the low perception of PCPs' self-efficacy, providing
      efficient strategies to PCPs and interdisciplinary health care teams for
      management of obesity is crucial. TRIAL REGISTRATION: Clinicaltrials.gov
      Identifier: NCT00991640.

PMID- 26217507
TI  - Bariatric psychology in the UK National Health Service: input across the patient
      pathway.
AB  - BACKGROUND: Providers of bariatric surgery within the National Health Service
      (NHS) are required to provide psychological assessment and intervention, yet
      operational definitions regarding the purpose and scope of this input are
      lacking. This has led to significant variation in the provision of psychology,
      with some providing an assessment-only service and others providing a more
      comprehensive package of intervention throughout the patient pathway. The aims of
      this paper are to document the current psychology provision and service models of
      National Health Service (NHS) bariatric surgery services in the UK. Psychologists
      belonging to a bariatric psychology forum completed a survey. This focused on
      provision of psychological assessment and intervention throughout the bariatric
      pathway as well as the ratio between psychology resources and number of bariatric
      procedures per year. We obtained information from 22 NHS services which provide
      3691 procedures per year. RESULTS: There is significant variation in the ratio
      between psychology resources and number of bariatric procedures undertaken per
      service. Whilst all services offer pre-surgery psychology assessments, less than
      one-third routinely assess all potential bariatric surgery candidates. Over 90%
      of services offer pre-surgery individual interventions and 41% offer pre-surgery
      groups. None of the services routinely offer post-surgery assessments but 68%
      offer post-surgery assessment and intervention following referral. None offered
      post-operative structured psychological group interventions. CONCLUSION: There
      are significant disparities and inconsistencies in the provision of psychology
      resources in relation to surgery volume in the NHS. Most of these resources are
      directed at pre-surgery assessment and this raises issues regarding the function
      of these assessments. Rather than focusing on assessing psychological
      (un)suitability for surgery, an evidence-based approach involves psychologists
      offering pre-operative interventions to improve readiness for surgery and post
      operative interventions to address recurring or emerging difficulties which
      impact on outcomes.

PMID- 26217508
TI  - The effect of menu labeling with calories and exercise equivalents on food
      selection and consumption.
AB  - BACKGROUND: Better techniques are needed to help consumers make lower calorie
      food choices. This pilot study examined the effect of menu labeling with caloric
      information and exercise equivalents (EE) on food selection. Participants, 62
      females, ages 18-34, recruited for this study, ordered a fast food meal with
      menus that contained the names of the food (Lunch 1 (L1), control meal). One week
      later (Lunch 2 (L2), experiment meal), participants ordered a meal from one of
      three menus with the same items as the previous week: no calorie information,
      calorie information only, or calorie information and EE. RESULTS: There were no
      absolute differences between groups in calories ordered from L1 to L2. However,
      it is noteworthy that calorie only and calorie plus exercise equivalents ordered
      about 16% (206 kcal) and 14% (162 kcal) fewer calories from Lunch 1 to Lunch 2,
      respectively; whereas, the no information group ordered only 2% (25 kcal) fewer.
      CONCLUSIONS: Menu labeling alone may be insufficient to reduce calories; however,
      further research is needed in finding the most effective ways of presenting the
      menu labels for general public.

PMID- 26217509
TI  - Effectiveness of mobile electronic devices in weight loss among overweight and
      obese populations: a systematic review and meta-analysis.
AB  - BACKGROUND: Mobile electronic devices, such as mobile phones and PDAs, have
      emerged as potentially useful tools in the facilitation and maintenance of weight
      loss. While RCTs have demonstrated a positive impact of mobile interventions, the
      extent to which mobile electronic devices are more effective than usual care
      methods is still being debated. RESULTS: Electronic databases were systematically
      searched for RCTs evaluating the effectiveness of mobile electronic device
      interventions among overweight and obese adults. Weighted mean difference for
      change in body weight was the primary outcome. The search strategy yielded 559
      citations and of the 108 potentially relevant studies, six met the criteria. A
      total of 632 participants were included in the six studies reporting a mean
      change in body weight. Using a random-effects model, the WMD for the effect of
      using mobile electronic devices on reduction in body weight was -1.09 kg (95% CI 
      2.12, -0.05). When stratified by the type of mobile electronic device used, it
      suggests that interventions using mobile phones were effective at achieving
      weight loss, WMD = -1.78 kg (95% CI -2.92, -0.63). CONCLUSIONS: This systematic
      review and meta-analysis suggests that mobile electronic devices have the
      potential to facilitate weight loss in overweight and obese populations, but
      further work is needed to understand if these interventions have sustained
      benefit and how we can make these mHealth tools most effective on a large scale.
      As the field of healthcare increasingly utilizes novel mobile technologies, the
      focus must not be on any one specific device but on the best possible use of
      these tools to measure and understand behavior. As mobile electronic devices
      continue to increase in popularity and the associated technology continues to
      advance, the potential for the use of mobile devices in global healthcare is
      enormous. More RCTs with larger sample sizes need to be conducted to look at the
      cost-effectiveness, technical and financial feasibility of adapting such mHealth
      interventions in a real clinical setting.

PMID- 26217510
TI  - Effects of workplace-based dietary and/or physical activity interventions for
      weight management targeting healthcare professionals: a systematic review of
      randomised controlled trials.
AB  - BACKGROUND: The prevalence of overweight and obesity is high amongst healthcare
      professionals and there is growing interest in delivering weight loss
      interventions in the workplace. We conducted a systematic review to (i) examine
      the effectiveness of workplace-based diet and/or physical activity interventions
      aimed at healthcare professionals and to (ii) identify and describe key
      components of effective interventions. Seven electronic databases were
      systematically searched. RESULTS: Thirteen randomised controlled trials met the
      inclusion criteria, of which seven had data available for meta-analysis. Where
      meta-analysis was possible, studies were grouped according to length of follow-up
      (<12 months and >=12 months) and behavioural target (diet only, physical activity
      only or diet and physical activity), with outcome data pooled using a weighted
      random effects model. Nine studies reported statistically significant (between
      group) differences. Four studies reported being informed by a behaviour change
      theory. Meta-analysis of all trials reporting weight data demonstrated healthcare
      professionals allocated to dietary and physical activity interventions lost
      significantly more body weight (-3.95 Kg, [95% CI -4.96 to- 2.95 Kg]) than
      controls up to 12 months follow up. CONCLUSIONS: Workplace diet and/or physical
      activity interventions targeting healthcare professionals are limited in number
      and are heterogeneous. To improve the evidence base, we recommend additional
      evaluations of theory-based interventions and adequate reporting of intervention
      content.

PMID- 26217511
TI  - Cardiac natriuretic peptides in plasma increase after dietary induced weight loss
      in obesity.
AB  - BACKGROUND: Cardiac natriuretic peptides are established biomarkers in heart
      disease, but are also affected by body mass index (BMI). The purpose of the
      present study was to examine the impact of weight loss and changes in body
      composition following dietary intervention on plasma concentrations of the
      prohormones to A- and B-type natriuretic peptides (proANP and proBNP) and
      adrenomedullin (proADM). RESULTS: A total of 52 healthy obese subjects, 47 women
      and 5 men (BMI 36.5 +/- 5.6 kg/m(2)) were randomised to either an intensive
      weight reduction programme using a combination of very low calorie diet (810
      kcal/day) and conventional hypo-energetic diet (1200 kcal/day) for 52 weeks, or
      to a control group that was offered diet-related counselling. N-terminal proBNP
      (NT-proBNP), mid-regional proANP (MR-proANP) and proADM (MR-proADM) and body
      composition using dual-energy x-ray absorptiometry (DEXA) scanning were
      determined at baseline and after 52 weeks. Comparisons between groups were
      analysed using t-tests. Changes from the baseline within the groups were analysed
      with paired tests. Changes in the variables, delta (?), were calculated as 52
      weeks minus the baseline. In the intervention group, BMI decreased by almost 20%
      (31.6 +/- 6.2 vs. 37.1 +/- 6.1 kg/m(2); P <0.001) with a loss of body fat of 23.5
      +/- 15.5% (P < 0.001). Plasma concentrations of NT-proBNP and MR-proANP increased
      (from 55 +/- 31 to 97 +/- 55 pg/ml; P < 0.001, and from 59 +/- 21 to 74 +/- 26
      pmol/L; P < 0.001), whereas MR-proADM decreased (from 573 +/- 153 to 534 +/- 173
      pmol/L; P <0.001). Changes (Delta) in MR-proANP correlated with Deltafat mass (r
      = -0.359; P = 0.011) and Deltaglucose (r = -0.495; P <0.001), while increases in
      NT-proBNP were primarily associated with reduced plasma glucose (r = -0.462; P
      <0.001). A modest but significant weight loss of 6% (P < 0.001) was found in the
      control group with no changes in plasma concentrations of NT-proBNP or MR-proANP,
      and a minor change in MR-proADM. CONCLUSIONS: Plasma NT-proBNP and MR-proANP
      concentrations increase and MR-proADM concentration decreases during weight loss,
      underlining the dynamic impact of BMI, body composition and glucose metabolism on
      these cardiovascular biomarkers.

PMID- 26217512
TI  - Self-perceived vs actual and desired weight and body mass index in adult
      ambulatory general internal medicine patients: a cross sectional study.
AB  - BACKGROUND: No study has compared patients' self-reported heights and weights
      (and resultant self-reported body mass indexes [BMIs]) with their actual heights,
      weights, and BMIs; their self-perceived BMI categories; and their desired weights
      and BMIs and determined rates of clinicians' documented diagnoses of overweight
      and obesity in affected patients in a single patient group. The objectives of
      this study were to make these comparisons, determine patient factors associated
      with accurate self-perceived BMI categorization, and determine the frequency of
      clinicians' documented diagnoses of overweight and obesity in affected patients.
      RESULTS: A total of 508 consecutive adult general internal medicine outpatients
      (257 women, 251 men; mean age, 62.9 +/- 14.9 years) seen at Mayo Clinic in
      Rochester, Minnesota, between November 9 and 20, 2009, completed a questionnaire
      in which they reported their heights, weights, self-perceived BMI categories
      ("underweight," "about right," "overweight," or "obese"), and desired weights.
      These self-reported data were compared to actual heights, actual weights, and
      actual BMI categories (measured after the questionnaire was completed). Overall,
      70% of the patients were overweight or obese. The average self-reported weight
      was significantly lower than the average actual weight (80.3 +/- 20.1 kg vs 81.9
      +/- 21.1 kg; P < .001). The average self-reported BMI was significantly lower
      than the average actual BMI (27.6 +/- 5.7 kg/m(2) vs 28.3 +/- 6.1 kg/m(2); P <
      .001). Overall, 32% of patients had obesity; however, only 6% perceived they were
      obese. Accuracy of self-perceived BMI category decreased with higher actual BMI
      category (P < .001 for trend). Female sex, higher education level, smoking
      status, and lower BMI were associated with higher accuracy of self-perceived BMI
      category. Desired weight loss increased with higher self-perceived and actual BMI
      categories (P < .001 for trends). Of the 165 patients who actually were obese,
      only 40 (24%) had obesity documented as a diagnosis in their medical records by
      their clinicians. Statistical tests used were the paired t test, the Pearson chi2
      test, the Cochrane-Armitage trend test, the Wald test of marginal homogeneity,
      analysis of variance, and univariate and multivariate logistic regression.
      CONCLUSIONS: Many obese patients inaccurately perceive their BMI categories;
      accuracy decreases with increasing BMI. Clinicians should inform patients of
      their BMIs and prescribe treatment plans for those with overweight and obesity.

PMID- 26217513
TI  - The correlation between supermarket size and national obesity prevalence.
AB  - BACKGROUND: Supermarkets provide healthy and affordable food options while
      simultaneously heavily promoting energy-dense, nutrient-poor foods and drinks.
      Store size may impact body weight via multiple mechanisms. Large stores encourage
      purchasing of more food in a single visit, and in larger packages. In addition
      they provide greater product choice (usually at lower prices) and allow greater
      exposure to foods of all types. These characteristics may promote purchasing and
      consumption. Our objective was to assess the relationship between supermarket
      size and obesity, which has rarely been assessed. RESULTS: Data on supermarket
      size (measured as total aisle length in metres) was from 170 stores in eight
      developed countries with Western-style diets. Data for national obesity
      prevalence was obtained from the UK National Obesity Observatory. We found a
      strong correlation between average store size and national obesity prevalence (r
      = 0.96). CONCLUSIONS: Explanations for the association between store size and
      national obesity prevalence may include larger and less frequent shopping trips
      and greater choice and exposure to foods in countries with larger stores. Large
      supermarkets may represent a food system that focuses on quantity ahead of
      quality and therefore may be an important and novel environmental indicator of a
      pattern of behaviour that encourages obesity.

PMID- 26217514
TI  - Body shape expectations and self-ideal body shape discrepancy in women seeking
      bariatric surgery: a cross-sectional study.
AB  - BACKGROUND: Postoperative body shape expectations (BSE) of bariatric surgery
      candidates remain relatively unexplored, and may have important implications for
      weight loss outcomes, treatment satisfaction, and education. METHODS: The
      'Silhouette Figure Rating Scale' was administered to 69 consecutive female
      candidates. Self-perceived current and goal body shape and postoperative BSE in
      four categories; "dream, "happy", "acceptable", and "disappointed" were examined.
      RESULTS: The mean age and BMI of the sample was 43.4 +/- 8.9 years and 48.8 +/-
      7.0 kg/m(2). Self-ideal body shape discrepancy of 4.1 +/- 1.3 silhouettes was
      reported, indicating body image dissatisfaction. 53% incorrectly identified the
      silhouette associated with their actual BMI. Goal body shape (4.3 +/- 0.8
      silhouettes) corresponded to a BMI figure 23.1 kg/m(2)- 26.2 kg/m(2). The
      postoperative "dream" (4.1 +/- 1.0 silhouettes), "happy" (5.0 +/- 0.8
      silhouettes), "acceptable" (5.3 +/- 1.0 silhouettes), and "disappointed" (6.9 +/-
      1.0 silhouettes) BSE corresponded to silhouettes that were thinner than the
      thinnest silhouette clinically expected based on a 56.1% excess weight loss 1
      year after laparoscopic sleeve gastrectomy (LSG) or a 22.3% to 47.2% total body
      weight loss. CONCLUSIONS: Women seeking bariatric surgery experience body image
      dissatisfaction and misperceive their actual body size. BSE do not correspond
      with evidence-based LSG weight loss outcomes.

PMID- 26217515
TI  - Challenges in lifestyle and community interventions research; a call for
      innovation.
AB  - Earlier this year the BMC portfolio was enriched by a new journal BMC Obesity.
      Here, we present the aims and objectives of the section on Lifestyle and
      Community Interventions. Innovative research is needed. Preventing or managing
      obesity requires addressing different determinants across multiple levels where
      diverse levers and stakeholders can play a critical role. Interactions of these
      determinants within and between systems need to be studied. How to leverage,
      manage and measure this complexity underlies the innovation that is needed in the
      next generation of obesity interventions. The ambition of the Lifestyle and
      Community Interventions section is to provide a space for innovative research,
      including research that falls outside the traditional comfort zone. We welcome
      studies of heterogeneous designs, including those of qualitative, quantitative,
      mixed and systems methodologies. Studies of interest include not only outcomes
      research of interventions but also process evaluation, cost-effectiveness or cost
      benefit analysis, and implementation and dissemination research. Innovations that
      integrate diverse intervention levers or combine primary and secondary levels of
      prevention are particularly encouraged. The general aim of BMC Obesity's
      Lifestyle and Community Interventions section is to advance our ability to decide
      on what combinations of approaches will be required to effectively and equitably
      prevent obesity. 

PMID- 26217517
TI  - Prevalence of overweight and obesity among primary school children in a
      developing country: NW-CHILD longitudinal data of 6-9-yr-old children in South
      Africa.
AB  - BACKGROUND: Widespread trends of increasing child obesity are reported in
      developing countries. This longitudinal NW-CHILD study investigated changes in
      overweight and obesity over a three year period among 574 children between the
      ages 6 and 9 (282 boys, 292 girls; 407 black, 143 white) in South Africa (SA),
      taking into consideration sex, race and school type. Stratified random sampling
      was used to identify 20 schools, across 5 school SES levels (quintiles), in 4
      educational districts of the North West Province of SA. Standard anthropometric
      techniques and international age adjusted BMI cut-off points for children were
      used to determine overweight and obesity, 3-years apart. Mixed models were used
      to analyse the effects of sex, race and socio-economic status (SES) of the
      school. RESULTS: Overall obesity increased over 3-years by 4% from 12.5% at
      baseline to 16.7% during follow-up. Obesity increased significantly in both white
      (4.2%) and black (2.0%) children, although overall prevalence in the final year
      was double (27.3%) in white children compared to black children (13.3%).
      Prevalence in obesity increased more in boys (3.2%) compared to girls (2.4%),
      although girls showed a higher overall prevalence (18.5%). SES effects were
      significant where children in schools associated with higher SES, had the highest
      rate of increase and the highest prevalence of obesity. A significant change
      towards an unhealthy BMI was found in 9.2% of the group over the 3-year period,
      although a small percentage (3.0%) also transitioned towards a healthier BMI.
      CONCLUSIONS: Overall obesity prevalence rose significantly from 6-9-years.
      Obesity, compared to overweight, increased more during this period. Prevalence
      and rate of increase differed markedly in different sexes, race and SES, masking
      the extent of the problem. Shifting towards an unhealthy BMI was more common than
      obtaining a healthier BMI over the 3-year period. It also demonstrated the
      difficulty of breaking the cycle of obesity, once it had started. Early
      prevention strategies are needed based on the trends established in this study,
      with special attention to white children living in high SES regions, and black
      children in economic transition.

PMID- 26217516
TI  - Altered NK cell function in obese healthy humans.
AB  - BACKGROUND: Obesity is associated with an elevated risk for several types of
      cancer and thus a major health hazard. However, the mechanism between overweight
      and cancer susceptibility is still elusive. Leptin, mainly produced by adipocytes
      links food intake and energy expenditure. In addition, recent studies have shown
      an immunomodulatory impact of leptin on NK cells. The purpose of the present
      study was to investigate whether leptin stimulation of NK cells from obese humans
      leads to altered functions as compared to NK cells from lean subjects. On the
      basis of body mass index 20 healthy individuals were classified in two groups:
      normal weight (<25 kg/m(2)) and obese (>30 kg/m(2)). Peripheral blood mononuclear
      cells (PBMC) were isolated from blood samples. We used flow cytometry to assess
      differences in phenotype and activity markers (CD107a, CD178 and TRAIL) of PBMCs
      between both groups. Furthermore, we determined after short-term in vitro leptin
      stimulation the phosphorylation of JAK2, downstream target of the intracellular
      signaling cascade of the leptin receptor, by Western Blotting and numbers of NK
      cell-tumor-cell-conjugates as well as Granzyme(+) and IFN-gamma(+) NK cells by
      flow cytometry. Finally, the proliferative capacity of control and long-term (7
      days) leptin-stimulated NK cells was examined. RESULTS: As opposed to similar NK
      cell counts, the number of CD3(+)CD56(+) cells was significantly lower in obese
      compared to lean subjects. Human NK cells express the leptin receptor (Ob-R). For
      further determination of Ob-R, intracellular target proteins of PBMCs were
      investigated by Western Blotting. Phosphorylation of JAK2 was lower in obese as
      compared to normal weight subjects. Furthermore, significantly lower levels of
      TNF-related apoptosis-inducing ligand (TRAIL) as an NK cell functional marker in
      obese subjects were found. In vitro leptin stimulation resulted in a higher
      production of interferon-gamma in NK cells of normal weight subjects.
      Interestingly, long-term leptin stimulation had no significant influence on
      numbers of proliferating NK cells. CONCLUSIONS: NK cells from obese healthy
      humans show functional deficits and altered responses after in vitro leptin
      challenge.

PMID- 26217518
TI  - Polybrominated diphenyl ether congener, BDE-47, impairs insulin sensitivity in
      mice with liver-specific Pten deficiency.
AB  - BACKGROUND: The potential health effects of polybrominated diphenyl ethers
      (PBDEs) that are widely used as flame-retardants in consumer products have been
      attributed, in part, to their endocrine disrupting properties. The purpose of
      this study is to examine the in vivo effects of an early exposure to PBDEs on the
      development of insulin resistance in mice. RESULTS: The metabolic consequences of
      BDE-47 in mice with varying insulin sensitivities secondary to liver-specific
      activation of Akt (Pten (fl/fl);Alb (Cre)) and mTORC1 (Tsc1 (fl/fl);Alb (Cre)) as
      well as wild-type littermates, were studied. BDE-47, a dominant congener of PBDE,
      was given daily (1 mg/kg/day) for six weeks by oral gavage in young mice
      following weaning. At the end of the exposure, there were no significant
      differences in total body, liver, or white adipose tissue weights between the BDE
      47-treated vs. DMSO-treated mice for each respective genotype. Metabolic studies
      revealed significant impairment in insulin sensitivity in the BDE-47-treated Pten
      (fl/fl);Alb (Cre) mice, but not in wild-type or Tsc1 (fl/fl);Alb (Cre) mice. This
      was not accompanied by significant alterations in plasma insulin levels or
      hepatic triglyceride accumulation in the Pten (fl/fl);Alb (Cre) mice. The mean
      plasma BDE-47 level in the wild-type mice was 11.7 +/- 2.9 ng/g (wet weight).
      CONCLUSIONS: Our findings indicate that BDE-47 exposure during the early post
      natal period induces a mild disturbance in glucose metabolism in susceptible mice
      with increased baseline insulin sensitivity. These results suggest an interaction
      between BDE-47 and genetic factors that regulate insulin signaling, which may
      result in long-term consequences.

PMID- 26217519
TI  - Perceived discrimination and favourable regard toward underweight, normal weight
      and obese eating disorder sufferers: implications for obesity and eating disorder
      population health campaigns.
AB  - BACKGROUND: Obesity stigma has been shown to increase binge eating, whilst
      positive regard for eating disorders (EDs) may increase dietary restriction which
      can also lead to binge eating and weight gain. In the context of increasing
      prevalence of both obesity and EDs exploring community attitudes towards these
      illnesses may uncover new variables worthy of consideration in population health
      campaigns. The aim of the study was to explore community perceived stigma and
      conversely favourable regard toward eating disorder (ED) sufferers of varying
      weight status, and understand how the attitudes of obese individuals may differ
      from those of non-obese individuals. Data for this purpose were derived from
      interviews with individuals participating in a general population health survey.
      Vignettes of an underweight female with Anorexia Nervosa (AN), a normal weight
      male with an atypical eating disorder (NWED) and an obese female with Binge
      Eating Disorder (BED) were presented to three randomly selected sub-samples of n
      = 983, 1033 and 1030 respectively. Questions followed that assessed participants'
      attitudes towards and beliefs about the person described in the vignette and
      their eating behaviours. RESULTS: Sixty-six per cent of participants who
      responded to the obese BED vignette believed that there would be discrimination
      against the person described (primarily because of her weight). Corresponding
      figures were for the AN and NWED vignettes were 48% and 35%, respectively. A
      positive regard for weight-loss or body-image-enhancing ED behaviours was
      reported 'occasionally' or more often by 8.8% of respondents to the AN vignette
      and by 27.5% of respondents to the NWED vignette. Positive regard for ED
      behaviours was significantly more likely in obese participants (AN: 15%; NWED:
      43%). CONCLUSION: The findings support integrated ED and obesity prevention
      programs that address weight stigma and the social desirability of ED behaviours
      in vulnerable individuals.

PMID- 26217520
TI  - Research protocol: Management of obesity in patients with low health literacy in
      primary health care.
AB  - BACKGROUND: Socioeconomically disadvantaged adults are both more likely to be
      obese and have lower levels of health literacy. Our trial evaluates the
      implementation and effectiveness of primary care nurses acting as prevention
      navigators to support obese patients with low health literacy to lose weight.
      METHODS/DESIGN: A pragmatic cluster randomised trial will be conducted. Twenty
      practices in socioeconomically deprived areas, 10 each in Sydney and Adelaide,
      will be recruited and randomised to intervention and control groups. Twenty to 40
      eligible obese patients aged 40-70 years with a BMI >= 30 kg/m(2) and with low
      health literacy will be enrolled per practice. The intervention is based on the
      '5As' of the chronic disease model approach - Assess, Advise, Agree, Assist and
      Arrange - and the recommendations of the 2013 Clinical practice guidelines for
      the management of overweight and obesity in adults, adolescents and children in
      Australia. In the intervention practices, patients will be invited to attend a
      health check with the prevention navigator who will assess the patient's risk and
      provide brief advice, assistance with goal setting and referral navigation.
      Provider training and educational meetings will be held. The providers' attitudes
      to obesity, confidence in treating obesity and preventive care they provide to
      obese people with low health literacy will be evaluated through questionnaires
      and interviews. Patients' self-assessment of lifestyle risk factors, perception
      of preventive care received in general practice, health-related quality of life,
      and health literacy will be assessed in telephone interviews. Patients'
      anthropometric measures will be recorded and their health service usage will be
      determined via linkage to the Australian government-held medical and
      pharmaceutical data. DISCUSSION: Our trial will provide evidence for the
      effectiveness of practice nurses as prevention navigators to support better
      weight management for obese patients with low health literacy. TRIAL
      REGISTRATION: This trial is registered with the Australian New Zealand Clinical
      Trials Registry (ACTRN12614001021662). Date registered 24/09/2014.

PMID- 26217521
TI  - Primary health care-level interventions targeting health literacy and their
      effect on weight loss: a systematic review.
AB  - BACKGROUND: Enhancing individual's health literacy for weight loss is important
      in addressing the increasing burden of chronic disease due to overweight and
      obesity. We conducted a systematic review and narrative synthesis to determine
      the effectiveness of lifestyle interventions aimed at improving adults' knowledge
      and skills for weight loss in primary health care. The literature search included
      English-language papers published between 1990 and 30 June 2013 reporting
      research conducted within Organisation for Economic Cooperation and Development
      member countries. Twelve electronic databases and five journals were searched and
      this was supplemented by hand searching. The study population included adults
      (>=18 years old) with a body mass index (BMI) >=25 kg/m(2) and without chronic
      disease at baseline. We included intervention studies with a minimum 6 month
      follow-up. Three reviewers independently extracted data and two reviewers
      independently assessed study quality by using predefined criteria. The main
      outcome was a change in measured weight and/or BMI over 6 or 12 months. RESULTS:
      Thirteen intervention studies, all targeting diet, physical activity and
      behaviour change to improve individuals' knowledge and/or skills for weight loss,
      were included with 2,089 participants. Most (9/13) of these studies were of a
      'weak' quality. Seven studies provided training to the intervention deliverers.
      The majority of the studies (11/13) showed significant reduction in weight and/or
      BMI in at least one follow-up visit. There were no consistent associations in
      outcomes related to the mode of intervention delivery, the number or type of
      providers involved or the intensity of the intervention. CONCLUSIONS: There was
      evidence for the effectiveness of interventions that focussed on improving
      knowledge and skills (health literacy) for weight loss. However, there was
      insufficient evidence to determine relative effectiveness of individual
      interventions. The lack of studies measuring socio-economic status needs to be
      addressed in future research as the rates of obesity are high in disadvantaged
      population groups.

PMID- 26217522
TI  - Improved metabolic health among the obese in six population surveys 1986 to 2009:
      the Northern Sweden MONICA study.
AB  - BACKGROUND: The incidence of CVD is decreasing in spite of increasing BMI in the
      population. We examined trends in metabolic health among overweight and obese
      individuals and the influence of lifestyle and socioeconomic status. Six cross
      sectional population surveys in the Northern Sweden MONICA Study between 1986 and
      2009. 8 874 subjects 25 to 64 years participated (74% participation rate).
      Metabolic health was defined as a total cholesterol level below 5.0 mmol/l, blood
      pressure below 140/90 mmHg and not having diabetes. In 2009 the age span 25 to 74
      years was studied. RESULTS: The prevalence of metabolic health among obese
      subjects increased by 7.9 % per year (95% confidence interval 5.4; 10.5),
      reaching 21.0% in 2009. The corresponding figures for overweight subjects were
      5.9% per year (4.6; 7.3), reaching 18% in 2009, whereas for the normal-weight
      subjects, the increase was 6.2% per year (5.3; 7.2), reaching 39% in 2009. The
      prevalence of metabolic health among subjects with abdominal obesity increased by
      5.8% (4.6; 7.0) per year, reaching 17.3% in 2009. Among those with no abdominal
      obesity the increase was 6.2% (5.2; 7.1), reaching 38% in 2009 (p = <0.001 for
      all groups). Only among non-obese men and obese women did the increase continue
      between 2004 and 2009. In the other groups a slight decline or levelling off was
      noted. In 2009 women had a 27% higher prevalence of metabolic health than men.
      The prevalence of metabolic health among the obese was 19.8% which declined to
      15.8% if subjects treated for hypertension or hypercholesterolemia were
      classified as not healthy. Overweight and obese subjects were less often
      metabolically healthy (odds ratio 0.54 and 0.59 respectively) compared with
      normal-weight subjects, independent of sex and age as were subjects with
      abdominal obesity (odds ratio 0.52). Adjustments for smoking, physical activity
      and education level did not influence any estimates. CONCLUSIONS: This report
      shows a large increase in prevalence of metabolic health from 1986 to 2009 for
      all anthropometric categories. Metabolic health remains considerably less
      prevalent among overweight and obese subjects than among those with normal
      weight.

PMID- 26217523
TI  - Plasma branched-chain and aromatic amino acid concentration after ingestion of an
      urban or rural diet in rural Mexican women.
AB  - BACKGROUND: People living in rural areas are prone to move to urban cities
      experiencing a dramatic change in the type of protein consumed. However, it is
      not know if those changes are associated with changes in the plasma amino acid
      concentration, especially the branched chain amino acids. Thus, the aim of the
      present study was to evaluate, in a rural Mexican population, the plasma amino
      acid profile after consumption of typical Mexican rural or urban diet. RESULTS:
      We evaluated the plasma amino acid concentrations of women from a rural
      population at 0, 30, 60, 90, 120, 180 and 240 min after ingestion of a typical
      Mexican rural or urban diet. Ingestion of a Mexican urban diet induced a higher
      increase in leucine, isoleucine, valine, phenylalanine, tyrosine and proline than
      ingestion of a Mexican rural diet in women from a Mexican rural population.
      Arginine, histidine, lysine, threonine, alanine, glycine and serine had the same
      area under the curve regardless of the experimental diet. CONCLUSIONS: Ingestion
      of a Mexican urban diet induced a higher increase in leucine, isoleucine, valine,
      phenylalanine, tyrosine and proline than ingestion of a Mexican rural diet in
      women from a Mexican rural area.

PMID- 26217524
TI  - The relationship between early life modifiable risk factors for childhood
      obesity, ethnicity and body mass index at age 3 years: findings from the Born in
      Bradford birth cohort study.
AB  - BACKGROUND: Many modifiable risk factors in early infancy have been shown to be
      associated with childhood overweight and obesity. These risk factors have not
      been studied within children of South Asian origin in the UK. The aims of this
      paper are to describe differences in the prevalence of modifiable risk factors
      for childhood obesity between children of White British and Pakistani origin and
      investigate the association between these risk factors and childhood BMI measured
      at age 3 years. We used data from a sub-study of the Born in Bradford birth
      cohort with detailed follow-up visits throughout early childhood. 987
      participants with a BMI measurement at age 3 were included; 39% were White
      British, 48% were of Pakistani origin and 13% were of other ethnicities. Linear
      and Poisson regression models were used to assess the association between risk
      factors and two outcomes at age 3; BMI z-scores and child overweight. RESULTS:
      Compared to Pakistani mothers, White British mothers were more likely to smoke
      during pregnancy, have higher BMI, breastfeed for a shorter duration and wean
      earlier, while Pakistani mothers had higher rates of gestational diabetes and
      were less active. There was no strong evidence that the relationship between risk
      factors and BMI z-score differed by ethnicity. There were associations between
      BMI z-score and maternal smoking (mean difference in BMI z-score 0.33 (95% CI
      0.13, 0.53)), maternal obesity (0.37 (0.19, 0.55)), indulgent feeding style (0.15
      (-0.06, 0.36)), lower parental warmth scores (0.21 (0.05, 0.36)) and higher
      parental hostility scores (0.17 (0.01, 0.33)). Consistent associations between
      these risk factors and child overweight were found. Mean BMI and the relative
      risk of being overweight were lower in children of mothers with lower parental
      self-efficacy scores and who watched more hours of TV. Other risk factors
      (gestational diabetes, child diet, child sleep, child TV viewing and maternal
      physical activity) were not associated with BMI. CONCLUSIONS: Whilst the
      prevalence of risk factors that have been associated with childhood greater BMI
      differ between White British and Pakistani the magnitude of their associations
      with BMI are similar in the two groups.

PMID- 26217525
TI  - Volumetric analysis of central body fat accurately predicts incidence of diabetes
      and hypertension in adults.
AB  - BACKGROUND: Central adipose tissue is appreciated as a risk factor for
      cardiometabolic disorders. The purpose of this study was to determine the
      efficacy of a volumetric 3D analysis of central adipose tissue in predicting
      disease. Full body computerized tomography (CT) scans were obtained from 1225
      female (518) and male (707) subjects, aged 18-88. Percent central body fat (%cBF)
      was determined by quantifying the adipose tissue volume from the dome of the
      liver to the pubic symphysis. Calcium score was determined from the calcium
      content of coronary arteries. Relationships between %cBF, BMI, and several
      cardiometabolic disorders were assessed controlling for age, sex, and race.
      RESULTS: Higher %cBF was significantly greater for those with type 2 diabetes and
      hypertension, but not stroke or hypercholesterolemia. Simple anthropometric
      determination of BMI equally correlated with diabetes and hypertension as central
      body fat. Calcium scoring significantly correlated with all measurements of
      cardiovascular health, including hypertension, hypercholesterolemia, and heart
      disease. CONCLUSIONS: Central body fat and BMI equally and highly predict
      incidence of hypertension and type 2 diabetes.

PMID- 26217526
TI  - Factors associated with participant retention in a clinical, intensive,
      behavioral weight management program.
AB  - BACKGROUND: We sought to identify factors associated with participant retention
      in a 2-year, physician-lead, multidisciplinary, clinical weight management
      program that employs meal replacements to produce weight loss and intensive
      behavioral interventions and financial incentives for weight loss maintenance. We
      studied 270 participants enrolled in 2010 and 2011. Sociodemographic factors,
      health insurance, distance traveled, body mass index, comorbidities, health
      related quality-of-life, and depression were explored as potential predictors of
      retention. RESULTS: Mean age was 49 +/- 8 years and BMI was 41 +/- 5 kg/m(2).
      Retention was excellent at 3 months (90%) and 6 months (83%). Attrition was
      greatest after participants were transitioned to regular foodstuffs and fell to
      67% at 12 months and 51% at 2 years. Weight decreased by 15 +/- 12 kg and BMI
      decreased by 5.1 +/- 4.0 kg/m(2) in 2-year completers. Older age, lower baseline
      BMI, and financial incentives for program participation were independently
      associated with retention. Fewer depressive symptoms at baseline were associated
      with retention. CONCLUSIONS: This multidisciplinary, clinical, weight management
      program demonstrated high retention and excellent outcomes. Older age at
      baseline, less extreme obesity, and financial incentives were associated with
      program retention.

PMID- 26217527
TI  - Television viewing time and risk of incident obesity and central obesity: the
      English longitudinal study of ageing.
AB  - BACKGROUND: Research suggests television viewing time may be associated with
      incident obesity and central obesity in young adults. No study has investigated
      these associations in older English adults. The aim of this study was to
      investigate longitudinal associations between television viewing time and
      incident obesity and central obesity in a sample of older English adults.
      Analyses of data from the English Longitudinal Study of Ageing. At baseline
      (2008), participants reported their television viewing time. Research nurses
      recorded obesity and central obesity by body mass index and waist circumference,
      respectively, at four year follow-up. Associations between television viewing
      time and incident obesity (BMI > 30 kg/m(2)) and central obesity (waist >102 cm
      men; > 88 cm women) at four year follow-up were examined using adjusted logistic
      regression. Participants gave full written informed consent to participate in the
      study and ethical approval was obtained from the London Multicentre Research
      Ethics Committee. RESULTS: A total of 3777 initially non-obese participants (aged
      64.8 +/- 8.6 yrs, 46.4% male) were included in the analyses using BMI as an
      outcome and 2947 for the analyses using waist circumference. No significant
      associations were found between television viewing time and incident obesity. A
      significant association was found between watching >=6 hrs/d of television
      (compared to <2 hrs/d) and central obesity (Odds Ratio 1.48; 95% confidence
      interval 1.07 to 2.03) after adjustment for covariables including physical
      activity. CONCLUSIONS: In this sample of older community dwelling English adults
      greater television viewing time was associated with incident central obesity, but
      not total obesity when measured by BMI. Interventions to reduce the incidence of
      central obesity in this age group that focus on reducing TV time, as well as
      targeting other health behaviours (eg, increasing physical activity levels,
      improving dietary intake) might prove useful.

PMID- 26217528
TI  - A systematic review of how researchers characterize the school environment in
      determining its effect on student obesity.
AB  - BACKGROUND: Obesity in early childhood is a robust predictor of obesity later in
      life. Schools provide unparalleled access to children and have subsequently
      become major intervention sites. However, empirical evidence supporting the
      effectiveness of school-based interventions against childhood obesity is of
      limited scope and unknown quality. The aim of this systematic review is to
      critically assess how researchers have characterized the school environment in
      determining its effect on childhood weight status in order to improve the quality
      and consistency of research in this area. We conducted a narrative review with a
      systematic search of the literature in line with PRISMA guidelines (2009).
      Original peer-reviewed research articles in English were searched from Medline,
      EMBASE, CENTRAL, CINAHL and PsycINFO databases from earliest record to January
      2014. We included empirical research that reported at least one measure of the
      primary/elementary school environment and its relationship with at least one
      objective adiposity-related variable for students aged 4-12 years. Two authors
      independently extracted data on study design, school-level factors, student
      weight status, type of analysis and effect. RESULTS: Five studies met the
      inclusion criteria. Each study targeted different parts of the school environment
      and findings across the studies were not comparable. The instruments used to
      collect school-level data report no validity or reliability testing. CONCLUSIONS:
      Our review shows that researchers have used instruments of unknown quality to
      test if the school environment is a determinant of childhood obesity, which
      raises broader questions about the impact that schools can play in obesity
      prevention.

PMID- 26217529
TI  - The cost-effectiveness of providing antenatal lifestyle advice for women who are
      overweight or obese: the LIMIT randomised trial.
AB  - BACKGROUND: Overweight and obesity during pregnancy is common, although robust
      evidence about the economic implications of providing an antenatal dietary and
      lifestyle intervention for women who are overweight or obese is lacking. We
      conducted a health economic evaluation in parallel with the LIMIT randomised
      trial. Women with a singleton pregnancy, between 10(+0)-20(+0) weeks, and BMI
      >=25 kg/m(2) were randomised to Lifestyle Advice (a comprehensive antenatal
      dietary and lifestyle intervention) or Standard Care. The economic evaluation
      took the perspective of the health care system and its patients, and compared
      costs encountered from the additional use of resources from time of randomisation
      until six weeks postpartum. Increments in health outcomes for both the woman and
      infant were considered in the cost-effectiveness analysis. Mean costs and effects
      in the treatment groups allocated at randomisation were compared, and incremental
      cost effectiveness ratios (ICERs) and confidence intervals (95%) calculated.
      Bootstrapping was used to confirm the estimated confidence intervals, and to
      generate acceptability curves representing the probability of the intervention
      being cost-effective at alternative monetary equivalent values for the outcomes
      avoiding high infant birth weight, and respiratory distress syndrome. Analyses
      utilised intention to treat principles. RESULTS: Overall, the increase in mean
      costs associated with providing the intervention was offset by savings associated
      with improved immediate neonatal outcomes, rendering the intervention cost
      neutral (Lifestyle Advice Group $11261.19+/-$14573.97 versus Standard Care Group
      $11306.70+/-$14562.02; p=0.094). Using a monetary value of $20,000 as a threshold
      value for avoiding an additional infant with birth weight above 4 kg, the
      probability that the antenatal intervention is cost-effective is 0.85, which
      increases to 0.95 when the threshold monetary value increases to $45,000.
      CONCLUSIONS: Providing an antenatal dietary and lifestyle intervention for
      pregnant women who are overweight or obese is not associated with increased costs
      or cost savings, but is associated with a high probability of cost effectiveness.
      Ongoing participant follow-up into childhood is required to determine the medium
      to long-term impact of the observed, short-term endpoints, to more accurately
      estimate the value of the intervention on risk of obesity, and associated costs
      and health outcomes. TRIALS REGISTRATION: Australian and New Zealand Clinical
      Trials Registry (ACTRN12607000161426).

PMID- 26217530
TI  - Associations of total and abdominal adiposity with risk marker patterns in
      children at high-risk for cardiovascular disease.
AB  - BACKGROUND: While body mass index percentiles (BMI%) are commonly used to assess
      childhood cardiovascular risk, waist circumference percentiles (WC%) are not
      commonly used nor universally accepted. We tested whether BMI% or WC% should be
      used to identify risk factor patterns in children at high-risk for developing
      cardiovascular disease (CVD). A total of 107 children (8-19 years) with
      cardiovascular risk factors or a family history of CVD were studied. Tobacco
      exposure, screen-time, blood pressure and anthropometric measures were made, as
      well as serum risk markers. Principal component analysis (PCA) was used to
      identify patterns explaining risk factor variance. Multiple linear regression was
      used to test for associations between risk factor patterns, BMI% and WC%.
      RESULTS: An adverse lipid pattern (low HDL, high triglycerides and LDL), a pro
      inflammatory pattern (high ICAM and TNFalphaR2), a high blood pressure pattern
      (high SBP and DBP) and a high Lp(a) pattern were identified. Higher BMI% and WC%
      were associated with significantly higher levels of the lipid pattern (p < 0.05).
      BMI% explained 20% of variance in this pattern, whereas WC% explained 22%. When
      both BMI% and WC% were used together, neither BMI% nor WC% were significantly
      associated with the lipid pattern. However, BMI% was significantly associated
      with lower levels of the pro-inflammatory pattern, and WC% was associated higher
      levels of the pro-inflammatory pattern - together explaining 12% of variance.
      CONCLUSION: In children at high-risk for CVD, BMI% or WC% explained similar
      variance in an adverse lipid pattern; however, the combination of BMI% and WC%
      explained greater variance in a pro-inflammatory pattern than either alone. Both
      WC% and BMI% should both be used in anthropometric assessments of high-risk
      children.

PMID- 26217531
TI  - Prevalence of obesity and overweight, its clinical markers and associated factors
      in a high risk South-Asian population.
AB  - BACKGROUND: Obesity is a global epidemic, which is a risk factor for
      cardiovascular diseases and metabolic abnormalities. It is measured by body mass
      index (BMI), waist circumference (WC), waist-hip ratio (WHR), body fat (BF)
      distribution and abdominal fat mass, each having its own merits and limitations.
      Variability in body composition between ethnic groups in South-Asians is
      significant and may not be truly reflected by BMI alone, which may result in
      misclassification. This study therefore, aims to determine the frequency of
      obesity, body fat composition and distribution, in a high risk population of an
      urban slum of Karachi, Pakistan. This survey included 451 participants selected
      by systematic sampling who were administered pre-tested questionnaires on socio
      demographics, diet and physical activity. Chi-square was used to determine the
      association between categorical variables and multiple linear regression was used
      for quantitative variables. A P value of less than 0.05 was considered
      significant. RESULTS: Classified by BMI, 29% study subjects were overweight and
      21% obese (58.7% with central obesity). Body fat percent (BF%) classified 81% as
      overweight. Females were more obese (P 0.03) with higher prevalence of central
      obesity (P <0.001) and WHR (P 0.003) but with a lower muscle mass (P 0.001).
      Activity score and muscle mass showed inverse linear association with BF%
      whereas, WC, weight, BMI and WHR had a positive linear association with BF%. The
      relationship between BMI and BF% was quadratic with a weaker association at lower
      BMI. Adjusting for socio-demographic variables, BF%, weight, diastolic blood
      pressure (DBP), BMI and score on the diet questionnaire had a positive linear
      association with WC, while WC, WHR and BP had a positive linear association with
      BF%. BF%, muscle content and WC had a positive linear association with BMI.
      CONCLUSION: Considering lower cut-offs for South-Asians BMI and WC, this study
      showed a high prevalence of obesity among a sub-urban population of Karachi,
      which was even higher when BF% was measured. Considering the rising prevalence of
      non-communicable diseases, BF%, WC, WHR and BMI measurements are convenient and
      feasible means of identifying population at risk and hence addressing it through
      public awareness and early detection.

PMID- 26217533
TI  - A randomised control trial assessing the impact of an investment based
      intervention on weight-loss, beliefs and behaviour after bariatric surgery: study
      protocol.
AB  - BACKGROUND: Although obesity surgery is currently the most effective method for
      achieving weight loss, not all patients lose the desired amount of weight and
      some show weight regain. Previous research shows that successful weight loss may
      be associated with the amount of investment the patient feels that they have made
      in their operation. For example, those who feel that it has taken more time and
      effort to organise, has cost more money, has been more disruptive to their lives
      and has caused pain are more likely to lose weight after their operation.
      Therefore, it seems as if the greater the sense of investment, the greater the
      motivation to make the operation a success. The present study aims to build on
      these findings by encouraging weight loss surgery patients to focus on the
      investment they have made, thus making their investment more salient to them and
      a means to improve weight loss outcomes. METHODS: The study involves an open
      randomised parallel group control trial with patients allocated either to the
      control or investment intervention group. Using third party blinded
      randomization, half the patients will be asked to rate and describe the
      investment they have made in their operation just before surgery then 3 and 6
      months after surgery. All patients will record their weight, beliefs about food,
      intentions to change and actual eating and exercise behaviour at baseline then 3,
      6 and 12 months follow up. Patients will be recruited from the bariatric surgery
      pre-assessment clinic at University College Hospital, London. The primary outcome
      is to explore the impact of the investment based intervention on patient's weight
      and BMI, with secondary outcomes of patients' beliefs about foods, behavioural
      intentions and diet and exercise behaviours. DISCUSSION: It is predicted that the
      investment intervention will improve excess weight loss post-surgery, together
      with beliefs about food, intentions to change and actual change in diet and
      exercise behaviour. This has cost implications for the NHS and other healthcare
      providers as improved effectiveness of bariatric surgery reduces the health costs
      of obese patients in the longer term and this simple, easy to administer and low
      cost intervention could become routine practice for bariatric patients. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier NCT02045628; December 2, 2013.

PMID- 26217532
TI  - Development of a theory-based, peer support intervention to promote weight loss
      among Latina immigrants.
AB  - BACKGROUND: Obesity rates are disproportionately high among Latinas living in the
      United States. Few community-based weight management studies have focused on
      Latina immigrants living in emerging Latino communities. The purpose of this
      study was to develop and pilot test a theory-based, promotora-delivered, peer
      support weight loss intervention for Latina immigrants to be administered in a
      community setting. We employed participatory methods to develop an 8-week program
      grounded in self-determination theory. Overweight Latina immigrants were
      recruited to participate in a quasi-experimental pilot study. Data collected pre
      and post-intervention included height, weight, fasting lipids, glucose, dietary
      practices, physical activity and depressive symptoms. RESULTS: Twenty-two women
      completed the intervention. Mean age was 36, mean time in the U.S. was 12 years;
      the majority was from Mexico. Mean BMI was 33; 68% had a family history of
      diabetes. The intervention resulted in statistically significant weight loss
      (mean 2.1 kg, SD 2.6, p < 0.001); mean change in weight remained significant when
      compared with that of a historical control group (-2.1 kg vs 1.10 kg, p < 0.01)
      but was attenuated at 6 months. Levels of moderate physical activity increased
      significantly (p < 0.05) and dietary practices improved (p < 0.01) and remained
      significant at 6 months. Notably, depressive symptoms also improved (p = <0.001).
      CONCLUSIONS: This theory-based, promotora-delivered intervention resulted in
      significant weight loss among a sample of Latina immigrants at 8 weeks. Future
      studies are needed to test the impact of an extended peer support intervention on
      long-term weight management. TRIAL REGISTRATION: National Clinical Trials:
      NCT02344212. Registered 21 January 2015.

PMID- 26217535
TI  - A formative evaluation of the SWITCH(r) obesity prevention program: print versus
      online programming.
AB  - BACKGROUND: SWITCH(r) is an evidence-based childhood obesity prevention program
      that works through schools to impact parenting practices. The present study was
      designed as a formative evaluation to test whether an online version of SWITCH(r)
      would work equivalently as the established print version. METHODS: Ten elementary
      schools were matched by socio-economic status and randomly assigned to receive
      either the print (n = 5) or online (n = 5) version. A total of 211 children from
      22, 3(rd) grade classrooms were guided through the 4 month program by a team of
      program leaders working in cooperation with the classroom teachers. Children were
      tasked with completing weekly SWITCH(r) Trackers with their parents to monitor
      goal setting efforts in showing positive Do (>=60 minutes of moderate-to-vigorous
      physical activity), View (<=2 hours of screen time), and Chew (>=5 servings of
      fruits and vegetables) behaviors on each day. A total of 91 parents completed a
      brief survey to assess project-specific interactions with their child and the
      impact on their behaviors. RESULTS: The majority of parents (93.2%) reported
      satisfactory experiences with either the online or print SWITCH(r) program. The
      return rate for the SWITCH(r) Trackers was higher (42.5% +/- 11%) from the print
      schools compared to the online schools (27.4% +/- 10.9%). District program
      managers rated the level of teacher engagement in regards to program facilitation
      and the results showed a higher Trackers return rate in the highly engaged
      schools (38.5% +/- 13.3%) than the lowly engaged schools (28.6 +/- 11.9%). No
      significant differences were observed in parent/child interactions or reported
      behavior change (ps > .05) suggesting the equivalence in intervention effect for
      print and online versions of the SWITCH(r) program. CONCLUSIONS: The findings
      support the utility of the online SWITCH(r) platform but school-based modules are
      needed to facilitate broader school engagement by classroom teachers and PE
      teachers.

PMID- 26217536
TI  - Using the RE-AIM framework to evaluate a community-based summer camp for children
      with obesity: a prospective feasibility study.
AB  - BACKGROUND: Increasing rates of childhood overweight and obesity highlight a need
      for the evaluation of lifestyle interventions. The purpose of the study was to
      determine the Reach, Effectiveness, Adoption, Implementation and Maintenance of a
      novel family-focused program targeting children with obesity (i.e., the
      Children's Health and Activity Modification Program [C.H.A.M.P.]) using the RE
      AIM framework, an evaluation tool for community-based health interventions.
      METHODS: A single-centre, single cohort interventional feasibility study was
      conducted over the course of two years. Children with obesity and their families
      completed a 4-week group-based lifestyle intervention in Year 1 (n = 15; M age =
      10.6; 53% female) and/or Year 2 (n = 25; M age = 10.6; 56% female). Outcome
      variables were measured pre- and post-intervention, as well as 6- and 12-months
      following completion of the formal program. RESULTS: Overall, C.H.A.M.P. had high
      reach in terms of participant representativeness. In addition, participation in
      the program was associated with significantly improved standardized body mass
      index (BMI-z), body fat percentage, lean mass percentage, and child- and parent
      proxy reported quality of life (QOL; effectiveness/individual maintenance).
      Furthermore, a number of community partnerships were built, strengthened, and
      maintained prior to, during, and following implementation of the two-year program
      (adoption/setting maintenance, respectively). Finally, the intervention was
      delivered as intended as evidenced by high adherence to the schedule, attendance
      rates, and cost effectiveness (implementation). CONCLUSIONS: Based on RE-AIM
      metrics, C.H.A.M.P. appears to be a promising childhood obesity program. The
      findings reported will inform researchers and practitioners on how to design and
      implement future community-based programs addressing pediatric obesity. TRIAL
      REGISTRATION: ISRCTN Registry, Study ID ISRCTN13143236. Registered 27 March 2015.

PMID- 26217537
TI  - A meta-analysis of weight gain in first year university students: is freshman 15
      a myth?
AB  - BACKGROUND: Observational studies report that as students transfer from secondary
      school to university, there is a tendency to gain weight. This phenomenon is
      known as the "Freshman 15" in North America, referring to the claim that on
      average weight gain is 15 lb (6.8 kg) in the first year of university. Studies
      since 1985 have mostly found weight gains ranging from 1 kg to 6 kg. Our meta
      analysis aimed to update the literature on the "Freshman 15" in the first year of
      university. We also aimed to explore weight gain in only those who gained weight
      and perform several subgroup analyses. Given adolescent weight gain is highly
      linked to overweight and obesity in adults, a better understanding of university
      student weight gain is crucial if we are to combat the rising adult obesity
      prevalence. METHODS: We conducted a search on six standard electronic databases
      (including PubMed, Embase, PsycInfo) from 1980 to 2014. Only peer reviewed
      articles with data from longitudinal studies were included. Screening was
      performed by two reviewers. The quality of papers was assessed and data
      extraction was done with a systematic approach. RESULTS: Thirty two studies were
      included and 22 studies (5549 students) were included in a pooled mean meta
      analysis as they reported standard errors. The overall pooled mean weight gain
      was 1.36 kg (3lbs) (95 % CI: 1.15 - 1.57) over an average of 5 months. A majority
      of students, 60.9 %, gained weight during freshman year and these on average
      gained 3.38 kg (7.5lbs) (95 % CI: 2.85 - 3.92). CONCLUSION: Freshman weight gain
      is an issue with almost two thirds of students gaining weight. Students who
      gained weight, gained it at rates much faster than in the general population.
      Despite most universities having some health promotion policies, we denote a
      consistent weight gain in university students across several countries.

PMID- 26217538
TI  - Welcome from the policies, socio-economic aspects, and health systems research
      section.
AB  - At BMC Obesity, the Policies, Socio-economic Aspects, and Health Systems Research
      Section provides an opportunity to submit research focussed on what we need to
      know to support implementation of obesity policies most likely to achieve
      substantial, sustainable and equitable reductions in the prevalence of obesity
      globally. Here, we present the aims and objectives of this section, hearing from
      each of the Associate Editors in turn. The ambition of the Policies, Socio
      economic Aspects, and Health Systems Research Section is to foster innovative
      research combining scientific quality with real world experience. We envisage
      this will include research addressing the structural drivers of obesity, solution
      oriented research, research addressing socio-economic inequalities in obesity and
      obesity prevention in low and middle income countries. We look forward to
      stimulating research to advance both the methods and substance required to drive
      uptake of effective and equitable obesity reduction policies globally. 

PMID- 26217539
TI  - Medication costs during an 18 month clinical trial of obesity treatment among
      patients encountered in primary care.
AB  - BACKGROUND: Weight loss often leads to reductions in medication costs,
      particularly for weight-related conditions. We aimed to evaluate changes in
      medication costs from an 18 month study of weight loss among patients recruited
      from primary care. METHODS: Study participants (n = 79, average age = 56.3; 75.7
      % female) with average BMI of 39.5 kg/m(2), plus one co-morbid condition of
      either diabetes/pre-diabetes, hypertension, abnormal cholesterol, or sleep apnea,
      were recruited from 2 internal medicine practices. All participants received
      intensive behavioral and dietary treatment during months 0-6, including
      subsidized access to portion-controlled foods for weight loss. From months 7-18,
      all participants were offered continued access to subsidized foods, and half of
      participants were randomly assigned to continue in-person visits ("Intensified
      Maintenance"), while the other half received materials by mail or e-mail
      ("Standard Maintenance"). Medication costs were evaluated at months 0, 6, and 18.
      RESULTS: Participants assigned to Intensified Maintenance maintained nearly all
      their lost weight, whereas those assigned to Standard Maintenance regained
      weight. However, no significant differences in medication costs were observed
      within or between groups during the 18 months of the trial. A reduction of nearly
      $30 per month (12.9 %) was observed among all participants from month 0 to month
      6 (active weight loss phase), but this difference did not reach statistical
      significance. CONCLUSIONS: A behavioral intervention that led to clinically
      significant weight loss did not lead to statistically significant reductions in
      medication costs. Substantial variability in medication costs and lack of a
      systematic approach by the study team to reduce medications may explain the lack
      of effect. TRIAL REGISTRATION: The trial was registered at (NCT01220089) on
      September 23, 2010.

PMID- 26217540
TI  - Efficacy of polyglucosamine for weight loss-confirmed in a randomized double
      blind, placebo-controlled clinical investigation.
AB  - BACKGROUND: The purpose of this clinical study was to ascertain whether low
      molecular weight chitosan polyglucosamine is able to produce significantly better
      weight loss than placebo. METHOD: 115 participants were included in the study. We
      used a two-center randomized, double blind, placebo-controlled design. The
      participants followed a standard treatment (ST), which included the combination
      of a low-calorie diet achieved through creating a daily calorie deficit (500 cal)
      and an increased daily physical activity (7 MET-h/week). They were randomized to
      receive standard treatment plus placebo (ST + PL) or standard treatment plus
      polyglucosamine (ST + PG), respectively. Participants were instructed to take 2 *
      2 tablets before the two meals containing the highest fat content for at least 24
      weeks. Body weight, BMI, waist circumference and the time needed for a 5 % body
      weight reduction (5R) were taken as main variables. RESULTS: The average weight
      loss over a period of 25 weeks in the ITT population was 5.8 +/- 4.09 kg in the
      ST + PG group versus 4.0 +/- 2.94 kg in the ST + PL (pU = 0.023; pt = 0.010).
      After 25 weeks, 34 participants achieved 5R in the ST + PG group (64.1 %)
      compared to only 23 participants in the ST + PL group (42.6 %) (ITT) (p Fisher =
      0.033). Weight loss through hypo-caloric diets have been found to be effective.
      The additional effect of PG in combination with standard treatment is able to
      produce significantly better weight loss than placebo. CONCLUSIONS: Participants
      treated with ST + PG showed a significant amount of weight loss, an additional
      1.8 kg, compared to controls treated with ST + PL. TRIAL REGISTRATION: Trial
      Registration at ClinicalTrials.gov: NCT02410785 Registered 07 April 2015.

PMID- 26217541
TI  - Maternal efficacy and sedentary behavior rules predict child obesity resilience.
AB  - BACKGROUND: To identify longitudinal individual, social and environmental
      predictors of adiposity (BMI z-score), and of resilience to unhealthy weight
      gain, in healthy weight children and adolescents. METHODS: Two hundred healthy
      weight children aged 5-12 years at baseline and their parents living in socio
      economically disadvantaged neighborhoods were surveyed at baseline and three
      years later. Children's height and weight were objectively measured, parents
      completed a detailed questionnaire that examined the home, social and
      neighborhood environments, and objective measures of the neighborhood environment
      were assessed using geographic information system data. Children classified as
      healthy weight at baseline who had small or medium increases in their BMI z-score
      between baseline and three year follow up (those in the bottom and middle
      tertiles) were categorized as 'resilient to unhealthy weight gain'. Where
      applicable, fully adjusted multivariable regression models were employed to
      determine baseline intrapersonal, social and environmental predictors of child
      BMI z-scores at follow-up, and resilience to unhealthy weight gain at follow-up.
      RESULTS: Maternal efficacy for preventing their child from engaging in sedentary
      behaviors (B = -0.03, 95 % CI: -0.06, 0.00) was associated with lower child BMI z
      score at follow up. Rules to limit sedentary behaviors (OR = 1.14, 95 % CI: 1.03,
      1.25) was a predictor of being resilient to unhealthy weight gain. CONCLUSION:
      The findings suggest that strategies to support parents to limit their children's
      sedentary behavior may be important in preventing unhealthy weight gain in
      socioeconomically disadvantaged communities.

PMID- 26217542
TI  - Dose and time responses of vitamin D biomarkers to monthly vitamin D3
      supplementation in overweight/obese African Americans with suboptimal vitamin d
      status: a placebo controlled randomized clinical trial.
AB  - BACKGROUND: A critical need exists to better understand the physiological sequel
      of vitamin D supplementation in obese individuals and African Americans. The aim
      was to comprehensively evaluate dose- and time-responses of a panel of vitamin D
      biomarkers to vitamin D supplements in this population. METHODS: We conducted a
      16-week randomized, double-blinded, and placebo-controlled clinical trial.
      Seventy overweight/obese African Americans (age 13-45 years, 84 % females) with
      25-hydroxyvitamin D [25(OH)D] concentrations <=20 ng/mL were randomly assigned to
      receive a supervised monthly oral vitamin D3 of 18,000 IU (~600 IU/day, n = 17),
      60,000 IU (~2000 IU/day, n = 18), 120,000 IU (~4000 IU/day, n = 18), or placebo
      (n = 17). RESULTS: There were significant dose- and time-responses of circulating
      25(OH)D, 1,25-dihydroxyvitamin D [1,25(OH)2D], and intact parathyroid hormone
      (iPTH), but not fibroblast growth factor-23 (FGF-23), phosphorus and urine
      calcium to the vitamin D supplements. The mean 25(OH)D concentrations in the 2000
      IU and 4000 IU groups reached >=30 ng/mL as early as 8-weeks and remained at
      similar level at 16-weeks. The increase of 25(OH)D was significantly higher in
      the 4000 IU group than all the other groups at 8-weeks. The increase of
      1,25(OH)2D was significantly higher in the 2000 IU and 4000 IU groups than the
      placebo at 8-weeks. Only the 4000 IU compared to the placebo significantly
      reduced iPTH at 8- and 16-weeks. CONCLUSIONS: Our RCT, for the first time,
      comprehensively evaluated time- and dose- responses of vitamin D supplementation
      in overweight/obese African Americans with suboptimal vitamin D status.
      Circulating 25(OH)D, 1,25(OH)2D, and iPTH, but not FGF-23, phosphorus and urine
      calcium, respond to vitamin D supplementation in a time- and dose-response
      manner. By monthly dosing, 2000 IU appears to be sufficient in achieving a
      25(OH)D level of 30 ng/mL in this population. However, importantly, 4000 IU,
      rather than 2000 IU, seems to suppress iPTH. If replicated, these data might be
      informative in optimizing vitamin D status and providing individualized dosing
      recommendation in overweight/obese African Americans. TRIAL REGISTRATION:
      ClinicalTrials.gov number: NCT01583621, Registered on April 3, 2012.

PMID- 26217543
TI  - Study protocol of the DUCATI-study: a randomized controlled trial investigating
      the optimal common channel length in laparoscopic gastric bypass for morbid obese
      patients.
AB  - BACKGROUND: Morbid obesity has become one of the most frequent chronic medical
      disorders in Western countries, affecting 1.5-2 % of the Dutch population.
      Currently, the laparoscopic Roux-Y gastric bypass is considered to be the most
      effective bariatric treatment option for morbid obesity as it results in adequate
      weight loss and a significant decrease in comorbidity. Although this technique
      has been applied for years, the optimal lengths of the three bowel limbs
      (alimentary limb, biliopancreatic limb, and common channel) in order to achieve
      maximal percentage excess weight loss with minimal side effects (i.e.
      malabsorption symptoms), are unknown. As 'normal' sized gastric bypasses achieve
      an average of 60 - 80 % excess weight loss after one year, one could hypothesize
      that afferent limb lengths should be longer in order to reduce the common channel
      length, thereby improving outcome in terms of excess weight loss. The aim of the
      current study is to investigate the effect of the length of the common channel in
      gastric bypass surgery for morbid obesity. In this randomized controlled trial
      the very long Roux limb gastric bypass will be compared to the standard gastric
      bypass, in order to conclude which option is the optimal therapeutic strategy in
      the morbidly obese patient. METHODS/DESIGN: In this multicentre trial patients
      will be randomized either to a very long Roux limb gastric bypass with a fixed
      common channel length of 100 cm, or to a standard gastric bypass with a variable
      common channel length. The primary objective is to evaluate whether the very long
      Roux limb gastric bypass is superior in terms of percentage excess weight loss
      after one year follow-up compared to the standard gastric bypass. Secondary
      endpoints are quality-of-life, cure /improvement of obesity related comorbidity,
      complications, malnutrition, re-admission rate, and re-operation rate.
      DISCUSSION: We hypothesize that our proposed distal LRYGB will provide for
      improved results concerning % EWL with an acceptable rate of (metabolic)
      complications. Our main point of interest is to determine if the distal LRYGB is
      a superior alternative to standard LRYGB in terms of percentage excess weight
      loss and to put more focus on the role of the common channel. Therefore we will
      perform this randomized controlled trial comparing both techniques, with % EWL as
      a primary outcome. TRIAL REGISTRATION: CCMO registration number: NL43951.101.13
      and Netherlands Trial Registry number: NTR4466.

PMID- 26217544
TI  - Does pneumococcal vaccination prevent myocardial infarction and stroke in elderly
      adults?

PMID- 26217545
TI  - Alien Limb Syndrome Responsive to Amantadine in a Patient with Corticobasal
      Syndrome.
AB  - BACKGROUND: Corticobasal syndrome (CBS) is a complex neurodegenerative disorder
      associated with parkinsonism and alien limb syndrome. Dressing and ideomotor
      apraxia were reportedly responsive to amantadine. CASE REPORT: A 79-year-old
      female was referred for evaluation of right hemiparesis. Neurological examination
      showed dementia, normal ocular movements, mild facial hypomimia, and bradykinesia
      with right hemiparesis. Nine years later, she developed alien limb syndrome and
      was diagnosed with CBS. After failure to respond to several medications, alien
      limb syndrome markedly improved with amantadine. DISCUSSION: To the best of our
      knowledge, this is the first report of a consistent response of severe, forced
      dystonic alien limb syndrome to amantadine in a patient with CBS.

PMID- 26217546
TI  - Training to Optimize Learning after Traumatic Brain Injury.
AB  - One of the major foci of rehabilitation after traumatic brain injury is the
      design and implementation of interventions to train individuals to learn new
      knowledge and skills or new ways to access and execute previously acquired
      knowledge and skills. To optimize these interventions, rehabilitation
      professionals require a clear understanding of how traumatic brain injury impacts
      learning, and how specific approaches may enhance learning after traumatic brain
      injury. This brief conceptual review provides an overview of learning, the impact
      of traumatic brain injury on explicit and implicit learning, and the current
      state of the science examining selected training approaches designed to advance
      learning after traumatic brain injury. Potential directions for future scientific
      inquiry are discussed throughout the review.

PMID- 26217547
TI  - A novel porcine bocavirus harbors a variant NP gene.
AB  - BACKGROUND: Porcine bocavirus is classified within the genus Bocaparvovirus,
      family Parvoviridae. Unlike other parvoviruses, the members of genus
      Bocaparvovirus (bocaparvoviruses) encode an additional open reading frame (NP1).
      Many strains of PBoVs have been identified in domestic pigs and recognized as a
      potential emerging pathogen causing respiratory and gastrointestinal disease.
      FINDINGS: A new strain of porcine bocavirus (PBoV) that harbored the shortest NP1
      gene among all currently characterized PBoVs (provisionally named as 'PBoV-KU14')
      was detected in domestic pigs. Almost the complete genome sequence was obtained,
      approximately 4,630 nucleotides in lengths with putative NS1, NP1, and VP1/2
      genes of 1,908, 600, 1,851 bp, respectively. Phylogenetic and comparative
      analysis was performed using protein and nucleotide sequences. It was revealed
      that PBoV-KU14 belongs to the genus Bocaparvovirus and species Ungulate
      bocaparvovirus 4. However, phylogenetic incongruence was observed among species
      classifications based on the NS1, NP1 and VP1/2 proteins, which indicates a
      probability of crossover recombination. Conserved protein domains unique for
      genus Bocaparvovirus in NP1, VP1 protein were also detected. CONCLUSION: NP1 gene
      truncation supposed to be caused by cross over recombination was detected in a
      new strain of PBoV (PBoV-KU14). Considering high rates of substitution and
      recombination in parvovirus, periodic surveillance study to monitor genomic
      variation and find new strainsof PBoVs seems to be needed.

PMID- 26217548
TI  - The utility of peritoneal drains in patients with perforated appendicitis.
AB  - BACKGROUND: Intra-abdominal abscesses are the most common complication after
      perforated appendicitis and remain a significant problem ranging in incidence
      from 14 to 18%. Drainage following appendectomy is usually determined by whether
      the underlying appendicitis is simple or complicated and largely determined by
      the surgeons' belief, based on expertise or personal opinion. In this report we
      discuss the results of patients diagnosed with peritoneal drainage, treated with
      or without a peritoneal drain. PATIENTS AND METHODS: A retrospective study of
      patients diagnosed with perforated appendicitis having surgery was performed.
      Patients diagnosed with perforated appendicitis treated with a peritoneal drain
      and patients treated without a peritoneal drain. Both groups were evaluated in
      terms of complications: intra-abdominal abscess, re-intervention, readmission and
      duration of hospital stay. RESULTS: 199 patients diagnosed with perforated
      appendicitis underwent appendectomy. 120 patients were treated without a
      peritoneal drain and 79 patients with a peritoneal drain. Thirty-one (26%)
      patients from the group without a peritoneal drain had a re-intervention compared
      to 9 (11%) in the group with a peritoneal drain (p = 0.013). Overall
      complications and readmission were also significantly lower in patients treated
      with a peritoneal drain. CONCLUSION: A peritoneal drain seems to reduce overall
      complication rate, re-intervention rate and readmission rate in patients treated
      with perforated appendicitis.

PMID- 26217549
TI  - Can cell proliferation of umbilical cord blood cells reflect environmental
      exposures?
AB  - Environmental hazards were shown to have an impact on cell proliferation (CP). We
      investigated CP of lymphocytes in umbilical cord blood in relation to prenatal
      environmental exposures in a sample of 346 Arab-Bedouin women giving birth in a
      local hospital. Information on subjects' addresses at pregnancy, potential
      household exposures and demographical status was collected in an interview during
      hospitalization. This population is usually featured by high rates of neonatal
      morbidity and multiple environmental exposures, originating from the local
      industrial park (IP), household hazards and frequent male smoking. A geometric
      mean CP ratio 2.17 (2.06; 2.29), and was high in women residing in a direction of
      prevailing winds from the local IP (p value = 0.094) and who gave birth during
      fall-winter season (p value = 0.024). Women complaining on disturbing exposure to
      noise had lower CP (p value = 0.015), compared to other women. CP was not
      indicative of neonatal morbidity. However, our findings suggest that CP of
      umbilical cord might be modified by environmental exposures. A long-term follow
      up of the children is required to assess their developmental outcomes. 

PMID- 26217550
TI  - Intraluminal pressure profiles during flexible ureterorenoscopy.
AB  - BACKGROUND: Irrigation and instrumentation during ureterorenoscopic procedures
      may cause increased pressure in the renal pelvis (PP) with potential harmful
      adverse effects. In order to assess the pressure increases during
      ureterorenoscopy, we measured the intraluminal renal pelvic pressure during
      retrograde intrarenal stone surgery (RIRS). METHODS: Twelve patients admitted for
      RIRS were included. Irrigation rate was standardized to 8 ml/min. A ureteral
      catheter was retrogradely placed in the renal pelvis for PP measurements. PP was
      measured one time per second during insertion of the Storz Flex-X2 ureteroscope
      and during stone treatment. RESULTS: Baseline PP was mean 10(+/-4.0) mmHg. During
      simple ureterorenoscopy, PP was mean 35(+/-10) mmHg. During stone management the
      average PP was 54(+/-18) mmHg and pelvic pressure peaks up to 328 mmHg occurred.
      In a 5-min standardized period of simple ureterorenoscopy, 83 pressure peaks >50
      mmHg were measured in average per patient (range 2-238). Forced irrigation with a
      20 ml syringe resulted in pressure peaks up to 288 mmHg. CONCLUSION: Very high
      pelvic pressures are obtained during flexible ureterorenoscopy. Taking into
      consideration that the threshold for pyelovenous backflow is around 30 mmHg, it
      is concerning that PPs >300 mmHg are not uncommon during these procedures.
      Methods to monitor and lower the PP during ureterorenoscopy, therefore, are
      considered of importance.

PMID- 26217551
TI  - An expression of uncertainty and its application to positioning: a quality-metric
      and optimal ranges for the identification of cells with RFID.
AB  - Here we devise an approach to model error and its propagation. Without
      approximations, we define the uncertainty of a measurement as its maximum
      possible error (maper). Thus, we propose and solve analytically two optimization
      problems. The one designed to determine the uncertainty of a measurement, the
      other specifically designed to optimize the accuracy of a RFID location system.
      The usefulness of this general approach is shown by applying it to the particular
      instance of estimating the coordinates of a person in real-time using RFID
      devices. This way, exact formulae to evaluate the quality of this measurement are
      mathematically deduced, which is useful, for example, to predict whether an
      inexpensive RFID location technology can meet a desired quality standard or not.
      The second optimization problem proposed here defines an optimal range (orange)
      for the RFID devices employed. Again, analytically, its exact formulae were
      derived. We propose an approach to distribute RFID tags for a positioning system
      based solely on RFID technology. In the light of the formulae, its quality is
      good enough as to locate emergency phone calls in real time. We found that key to
      an optimal performance is the range used and the distance between consecutive
      tags. 

PMID- 26217552
TI  - Prognostic value of SS18-SSX fusion type in synovial sarcoma; systematic review
      and meta-analysis.
AB  - SS18-SSX (formerly called SYT-SSX) fusion gene has been established clinically as
      a molecular diagnostic test for synovial sarcoma, but the prognostic value of the
      fusion gene variant for survival is controversial. The objective of this
      systematic review is to provide an up-to-date and unprecedented summary of the
      prognostic impact of SS18-SSX fusion type in synovial sarcoma. Studies evaluating
      SS18-SSX fusion type as a prognostic marker in synovial sarcoma were
      systematically searched for in MEDLINE, EMBASE, and Web of Science. Comparative
      analysis of the pooled hazard ratios (HR) between fusion types was carried out,
      in order to assess the likelihood of overall survival (OS), disease-specific
      survival (DSS), progression-free survival (PFS), and metastasis-free survival
      (MFS). A total of 10 studies comprising 902 patients with synovial sarcoma were
      considered for the meta-analysis. The pooled HR for eight eligible studies
      evaluating for OS or DSS was 1.28 (95% confidence interval: 0.81-2.00),
      suggesting no significant difference between SS18-SSX1 and SS18-SSX2 (P = 0.29).
      For seven studies which evaluated for PFS or MFS, the presence of SS18-SSX1 may
      indicate a lower survival probability than that of SS18-SSX2, although the effect
      did not reach a level of statistical significance (P = 0.09). There was no
      significant difference in OS or DSS between SS18-SSX1 and SS18-SSX2, but there
      were indications of SS18-SSX1 being an unfavorable prognostic factor of PFS or
      MFS. Further studies including cohorts with a longer follow-up period are needed.

PMID- 26217553
TI  - Combination chemotherapy with mitomycin C and methotrexate is active against
      metastatic HER2-negative breast cancer even after treatment with anthracycline,
      taxane, capecitabine, and vinorelbine.
AB  - BACKGROUND: Combination chemotherapy with mitomycin C and methotrexate (MM) was
      reported to be effective for 24% of patients with metastatic breast cancer (MBC)
      who had been treated with anthracycline and taxane. Antimetabolites such as
      capecitabine and antitubulins such as vinorelbine have been generally used for
      MBC treatment after anthracycline and taxane. A subsequent choice of chemotherapy
      should be offered to patients with MBC who have kept good performance status (PS)
      after being aggressively treated with anthracycline, taxane, capecitabine, and
      vinorelbine (ATCV), but is not well clear which treatment is superior to others
      after ATCV. In this study, we examined whether MM treatment is a good choice
      following ATCV. METHODS: We retrospectively reviewed the medical records of 31
      patients with HER2-negative metastatic breast cancer who were treated with MM
      following ATCV. One cycle of MM was defined as MMC 8 mg/m(2) on day 1 and MTX 60
      mg/m(2) on day 1 and day 15, administered intravenously every 4 weeks. RESULTS:
      Response rate and clinical benefit rate were 9.7 and 19.4%, respectively. Median
      times to progression and times to failure were 3.9 and 3.7 months, respectively.
      Adverse events of grade 3 and/or 4 were observed in 36% patients.
      Thrombocytopenia of grade 3 or 4 was 12.9 and 3.2%. Grades 3 and 4 of leucopenia
      and anemia were 12.9 and 9.7%, respectively. CONCLUSION: MM is effective and
      tolerable for MBC patients even after aggressive treatment with ATCV. MM is one
      treatment choice when patients have kept good PS and bone marrow function even
      after multiple regimens of chemotherapy.

PMID- 26217555
TI  - Appendiceal abscess in a giant left-sided inguinoscrotal hernia: a rare case of
      Amyand hernia.
AB  - The hernia of Amyand is an inguinal hernia containing the appendix in the sac. It
      is a rare pathology often diagnosed only intra-operatively. We report a case even
      more rare of a giant left-sided inguinoscrotal Amyand hernia with appendiceal
      abscess without clinical findings of incarceration/strangulation, occlusion,
      perforation, or acute scrotum and with the presence in the sac of the caecum and
      other anatomical structures (last ileal loops, bladder and omentum). The 68-years
      old man patient successfully underwent surgical treatment only through the hernia
      sac (meshless repair according to Postempski technique). 

PMID- 26217554
TI  - The effect of Katsura-uri (Japanese pickling melon, Cucumis melo var. conomon)
      and its derived ingredient methylthioacetic acid on energy metabolism during
      aerobic exercise.
AB  - PURPOSE: We investigated the effect of Katsura-uri (Japanese pickling melon;
      Cucumis melo var. conomon) on energy metabolism during exercise in human and
      animal studies. METHODS: Eight healthy men (mean age, 21.4 +/- 0.7 years)
      participated in a single-blind, crossover study. Thirty minutes after ingesting
      the Katsura-uri drink or placebo drink, they exercised on a cycle ergometer at
      40% maximal heart rate for 30 min. Respiratory gas analysis was performed during
      exercise to examine oxygen consumption and substrate utilization. Blood
      biochemical parameters were evaluated during exercise. In the animal study, the
      effect of methylthioacetic acid (MTA), a Katsura-uri derived component was
      examined in mice. Immediately after running at 25 m/min for 30 min, biochemical
      parameters in the hind limb muscle and blood of mice were measured. RESULTS:
      Oxygen consumption during exercise was higher in the Katsura-uri condition (19.8
      +/- 3.5 mL/kg/min) than the placebo condition (18.6 +/- 3.0 mL/kg/min) (P <
      0.05). The elevation of blood lactate was lower in the Katsura-uri condition (1.7
      +/- 0.4 mM) than the placebo condition (2.2 +/- 0.6 mM) 15 min after beginning
      exercise (P < 0.05). There was a higher positive correlation between lactate
      concentration and carbohydrate oxidation during exercise in the Katsura-uri
      condition (R(2) = 0.86) compared to the placebo condition (R(2) = 0.47). The
      decrease in intermuscular pH and the increase in blood lactate following exercise
      were prevented by MTA supplementation (250 ppm) with significant differences in
      the MTA-supplemented group compared to the control group. CONCLUSIONS: These
      results suggest that the ingestion of Katsura-uri and/or MTA improves glucose
      metabolism and acidification in skeletal muscles during exercise in human and
      animal studies.

PMID- 26217556
TI  - Microarray gene expression profiling reveals potential mechanisms of tumor
      suppression by the class I HDAC-selective benzoylhydrazide inhibitors.
AB  - Histone deacetylase (HDAC) inhibitors (HDIs) have therapeutic potentials for
      treating cancer and other diseases. Modulation of gene expression by HDIs is a
      major mechanism underlying their therapeutic effects. A novel class of HDIs with
      a previously undescribed benzoylhydrazide scaffold has been discovered through a
      high throughput screening campaign. Using microarray profiling of gene
      expression, we have previously demonstrated that treatment of breast cancer cells
      with a lead benzoylhydrazide HDI UF010 results in cell cycle arrest and
      apoptosis, likely through activation of tumor suppression pathways with
      concurrent inhibition of oncogenic pathways. In this brief report, we show
      methodological and analytical details and discuss additional pathways such as
      immune signaling that are affected by UF010. Raw and processed data from the
      microarray were deposited in NCBI's Gene Expression Omnibus (GEO) database under
      the accession number: GSE56823.

PMID- 26217557
TI  - The Current Position of Archives of Plastic Surgery and Its Future.

PMID- 26217558
TI  - A Review of Macrodystrophia Lipomatosa: Revisitation.
AB  - Macrodystrophia lipomatosa (MDL) is a rare congenital non-hereditary disorder
      that has significant impact on patient morbidity. This study provides a
      comprehensive review of the natural history, diagnosis, management, and outcomes
      of the disorder. A literature search in PubMed was conducted to identify cases of
      MDL from January 1950 to 14 February 2014. After ruling out articles without
      information related to the management of the disorder, a summary of 32 studies
      was performed. An additional three cases from the authors are also presented.
      Based on 57 journal articles and three additional cases from the authors, around
      108 cases of MDL were reviewed. Most patients were males who were admitted to a
      treatment clinic in the first four years of life. The lower extremities were more
      frequently affected, with unilateral presentation being most common. They
      commonly underwent a single-staged surgical procedure with follow-up periods
      ranging from more than one year up to 21 years. Out of 43 cases that underwent
      surgical procedures, 13 reported no complications, and there were seven cases of
      esthetic satisfaction and 15 cases of significant functional improvement.
      Depending on the severity of a patient's condition, the use of non-invasive
      diagnostic tools should be carefully considered. Surgery might be a better choice
      of management than observation, taking into account possible future complications
      in the absence of surgery and the beneficial outcomes of surgical procedures. 

PMID- 26217559
TI  - Relationship between Locations of Facial Injury and the Use of Bicycle Helmets: A
      Systematic Review.
AB  - The aim of this study is to review the protective effect of a bicycle helmet on
      each facial location systematically. PubMed was searched for articles published
      before December 12, 2014. The data were summarized, and the odds ratio (OR)
      between the locations of facial injury was calculated. A statistical analysis was
      performed with Review Manager (The Nordic Cochrane Centre). Bicycle helmets
      protect the upper and middle face from serious facial injury but do not protect
      the lower face. Non-wearers had significantly increased risks of upper facial
      injury (OR, 2.07; P<0.001) and of middle facial injury (OR, 1.97; P<0.001) as
      compared to helmet users. In the case of lower facial injury, however, only a
      slightly increased risk (OR, 1.42; 95% confidence interval (CI), 0.67-3.00,
      P=0.36) was observed. The abovementioned results can be attributed to the fact
      that a helmet covers the head and forehead but cannot cover the lower face.
      However, helmets having a chin cap might decrease the risk of lower facial
      injury. 

PMID- 26217560
TI  - Levels of Evidence in the Plastic Surgery Literature: A Citation Analysis of the
      Top 50 'Classic' Papers.
AB  - BACKGROUND: The plastic surgery literature is vast, consisting of a plethora of
      diverse articles written by a myriad of illustrious authors. Despite this
      considerable archive of published material, it remains nebulous as to which
      precise papers have had the greatest impact on our specialty. The aim of this
      study was to identify the most cited papers in the plastic surgery literature and
      perform a citation analysis paying particular attention to the evidence levels of
      the clinical studies. METHODS: We identified the 50 most cited papers published
      in the 20 highest impact plastic surgery journals through the Web of Science. The
      articles were ranked in order of number of citations acquired and level of
      evidence assessed. RESULTS: The top 50 cited papers were published in six
      different journals between the years 1957 and 2007. Forty-two of the papers in
      the top 50 were considered as level IV or V evidence. No level I or II evidence
      was present in the top 50 list. The average level of evidence of the top 50
      papers was 4.28. CONCLUSIONS: In the plastic surgery literature, no positive
      correlation exists between a high number of citations and a high level of
      evidence. Anatomical reconstructive challenges tend to be the main focus of
      plastic surgery rather than pathologic diseases and consequently, papers with
      lower levels of evidence are relatively more valuable in plastic surgery than
      many other specialties.

PMID- 26217561
TI  - Bone and Soft Tissue Changes after Two-Jaw Surgery in Cleft Patients.
AB  - BACKGROUND: Orthognathic surgery is required in 25% to 35% of patients with a
      cleft lip and palate, for whom functional recovery and aesthetic improvement
      after surgery are important. The aim of this study was to examine maxillary and
      mandibular changes, along with concomitant soft tissue changes, in cleft patients
      who underwent LeFort I osteotomy and sagittal split ramus osteotomy (two-jaw
      surgery). METHODS: Twenty-eight cleft patients who underwent two-jaw surgery
      between August 2008 and November 2013 were included. Cephalometric analysis was
      conducted before and after surgery. Preoperative and postoperative measurements
      of the bone and soft tissue were compared. RESULTS: The mean horizontal
      advancement of the maxilla (point A) was 6.12 mm, while that of the mandible
      (point B) was -5.19 mm. The mean point A-nasion-point B angle was -4.1 degrees 
      before surgery, and increased to 2.5 degrees  after surgery. The mean nasolabial
      angle was 72.7 degrees  before surgery, and increased to 88.7 degrees  after
      surgery. The mean minimal distance between Rickett's E-line and the upper lip was
      6.52 mm before surgery and 1.81 mm after surgery. The ratio of soft tissue change
      to bone change was 0.55 between point A and point A' and 0.93 between point B and
      point B'. CONCLUSIONS: Patients with cleft lip and palate who underwent two-jaw
      surgery showed optimal soft tissue changes. The position of the soft tissue
      (point A') was shifted by a distance equal to 55% of the change in the maxillary
      bone. Therefore, bone surgery without soft tissue correction can achieve good
      aesthetic results.

PMID- 26217562
TI  - Combined Orbital Fractures: Surgical Strategy of Sequential Repair.
AB  - BACKGROUND: Reconstruction of combined orbital floor and medial wall fractures
      with a comminuted inferomedial strut (IMS) is challenging and requires careful
      practice. We present our surgical strategy and postoperative outcomes. METHODS:
      We divided 74 patients who underwent the reconstruction of the orbital floor and
      medial wall concomitantly into a comminuted IMS group (41 patients) and non
      comminuted IMS group (33 patients). In the comminuted IMS group, we first
      reconstructed the floor stably and then the medial wall by using separate implant
      pieces. In the non-comminuted IMS group, we reconstructed the floor and the
      medial wall with a single large implant. RESULTS: In the follow-up of 6 to 65
      months, most patients with diplopia improved in the first-week except one, who
      eventually improved at 1 year. All patients with an EOM limitation improved
      during the first month of follow-up. Enophthalmos (displacement, 2 mm) was
      observed in two patients. The orbit volume measured on the CT scans was
      statistically significantly restored in both groups. No complications related to
      the surgery were observed. CONCLUSIONS: We recommend the reconstruction of orbit
      walls in the comminuted IMS group by using the following surgical strategy: usage
      of multiple pieces of rigid implants instead of one large implant, sequential
      repair first of the floor and then of the medial wall, and a focus on the
      reconstruction of key areas. Our strategy of step-by-step reconstruction has the
      benefits of easy repair, less surgical trauma, and minimal stress to the surgeon.

PMID- 26217563
TI  - The Usefulness of Leukosan SkinLink for Simple Facial Laceration Repair in the
      Emergency Department.
AB  - BACKGROUND: Repair of facial laceration in the emergency department can pose a
      number of difficulties. Children can be uncooperative, but adults can also be if
      they have sustained head trauma or are intoxicated. Leukosan SkinLink consists of
      topical adhesive and adhesive tape that can be applied easily to long or tense
      wounds. In this study, the authors compared conventional suturing with Leukosan
      SkinLink for facial laceration patients in the emergency department. METHODS: The
      prospective study was carried out from March 2013 to September 2013 with linear
      facial laceration patients visiting the emergency department. Exclusion criteria
      were open fractures, joint injuries, skin defects, hairy skin, and mucosa. The
      author used Leukosan SkinLink for skin closure in the experimental group and used
      conventional suturing in the control group. The scar evaluation using the Patient
      and Observer Scar Assessment Scale (POSAS) along with satisfaction scores,
      procedure times, and complications were compared. RESULTS: A total of 77 patients
      (30 in the control group and 47 in the experimental group) participated and
      underwent follow-up for 6 months postoperatively. The scar assessment using the
      POSAS and the satisfaction score in both groups were similar. The average
      procedure time in the experimental group was shorter. In the control group, there
      were four cases of wound dehiscence, two of infection, and one of skin necrosis,
      whereas four cases of wound dehiscence and one allergic reaction occurred in the
      experimental group. CONCLUSIONS: With a simple application technique, Leukosan
      SkinLink is a new effective method for facial laceration repair especially useful
      for children and uncooperative adults.

PMID- 26217564
TI  - Breast Auto-Augmentation: A Versatile Method of Breast Rehabilitation-A
      Retrospective Series of 107 Procedures.
AB  - BACKGROUND: Breast auto-augmentation (BAA) using an inferior pedicle
      dermoglandular flap aims to redistribute the breast tissue in order to increase
      the fullness in the upper pole and enhance the central projection of the breast
      at the time of mastopexy in women who want to avoid implants. The procedure
      achieves mastopexy and an increase in breast volume. METHODS: Between 2003 and
      2014, 107 BAA procedures were performed in 53 patients (51 bilateral, 2
      unilateral and 3 reoperations) with primary or secondary ptosis of the breast
      associated with loss of fullness in the upper pole (n=45) or undergoing
      explantation combined with capsulectomy (n=8). Six patients (11.3%) had prior
      mastopexy and 2 (3.7%) patients had prior reduction mammoplasty. The mean
      patients' age was 41 years (range, 19-66 years). All patients had preoperative
      and postoperative photographs and careful preoperative markings. Follow-up ranged
      from 6 months to 9 years (mean, 6.6 months). RESULTS: The range of elevation of
      the nipple was from 6 to 12 cm (mean, 8 cm). The wounds healed completely with no
      complications in 50 (94.3%) patients. Three patients had complications including
      2 (3.7%) hematomas and 1 (1.9%) partial necrosis of the nipple-areola complex.
      Three (5.7%) patients were dissatisfied with the level of mastopexy achieved
      underwent a further procedure. No patient complained of scar hypertrophy.
      CONCLUSIONS: BAA is a versatile technique for women with small breasts associated
      with primary or secondary ptosis. It is also an effective technique for the
      salvage of breasts after capsulectomy and explantation.

PMID- 26217565
TI  - Semicircular Horizontal Approach in Breast Reduction: Clinical Experience in 38
      Cases.
AB  - BACKGROUND: Various techniques are used for performing breast reduction. Wise
      pattern and vertical scar techniques are the most commonly employed approaches.
      However, a vertical scar in the mid-lower breast is prominent and aesthetically
      less pleasant. In contrast, a semicircular horizontal approach does not leave a
      vertical scar in the mid breast and transverse scars can be hidden in the
      inframammary fold. In this paper, we describe the experiences and results of
      semicircular horizontal breast reductions performed by a single surgeon. METHODS:
      Between September 1996 and October 2013, our senior author used this technique in
      38 cases in the US and at our institution. We used a superiorly based
      semicircular incision, where the upper skin paddle was pulled down to the
      inframammary fold with the nipple-areola complex pulled through the keyhole.
      RESULTS: The average total reduction per breast was 584 g, ranging from 286 to
      794 g. The inferior longitudinal pedicle was used in all the cases. The average
      reduction of the distance from the sternal notch to the nipple was 13 cm (range,
      11-15 cm). The mean decrease in the bra cup size was 1.7 cup sizes (range, a
      decrease of 1 to 3). We obtained very satisfactory results with a less noticeable
      scar, no complication such as necrosis of the nipple or the skin flap, wound
      infection, aseptic necrosis of the breast tissue, or wound dehiscence. One
      patient had a small hematoma that resolved spontaneously. CONCLUSIONS: This
      technique is straightforward and easy to learn, and offers a safe, effective, and
      predictable way for treating mammary hypertrophy.

PMID- 26217566
TI  - Lateral Oropharyngeal Wall Coverage with Buccinator Myomucosal and Buccal Fat Pad
      Flaps.
AB  - BACKGROUND: Reconstruction of oropharyngeal defects after resection of
      oropharyngeal cancer is a significant challenge. The purpose of this study is to
      introduce reconstruction using a combination of a buccinator myomucosal flap and
      a buccal fat pad flap after cancer excision and to discuss the associated
      anatomy, surgical procedure, and clinical applications. METHODS: In our study, a
      combination of a buccinator myomucosal flap with a buccal fat pad flap was
      utilized for reconstruction after resection of oropharyngeal cancer, performed
      between 2013 and 2015. After oropharyngectomy, the defect with exposed vital
      structures was noted. A buccinator myomucosal flap was designed and elevated
      after an assessment of the flap pedicle. Without requiring an additional
      procedure, a buccal fat pad flap was easily harvested in the same field and
      gently pulled to obtain sufficient volume. The flaps were rotated and covered the
      defect. In addition, using cadaver dissections, we investigated the feasibility
      of transposing the flaps into the lateral oropharyngeal defect. RESULTS: The
      reconstruction was performed in patients with squamous cell carcinoma. The
      largest tumor size was 5 cm*2 cm (length*width). All donor sites were closed
      primarily. The flaps were completely epithelialized after four weeks, and the
      patients were followed up for at least six months. There were no flap failures or
      postoperative wound complications. All patients were without dietary
      restrictions, and no patient had problems related to mouth opening, swallowing,
      or speech. CONCLUSIONS: A buccinator myomucosal flap with a buccal fat pad flap
      is a reliable and valuable option in the reconstruction of oropharyngeal defects
      after cancer resection for maintaining functionality.

PMID- 26217567
TI  - Functional Outcomes of Multiple Sural Nerve Grafts for Facial Nerve Defects after
      Tumor-Ablative Surgery.
AB  - BACKGROUND: Functional restoration of the facial expression is necessary after
      facial nerve resection to treat head and neck tumors. This study was conducted to
      evaluate the functional outcomes of patients who underwent facial nerve cable
      grafting immediately after tumor resection. METHODS: Patients who underwent cable
      grafting from April 2007 to August 2011 were reviewed, in which a harvested
      branch of the sural nerve was grafted onto each facial nerve division. Twelve
      patients underwent facial nerve cable grafting after radical parotidectomy, total
      parotidectomy, or schwannoma resection, and the functional facial expression of
      each patient was evaluated using the Facial Nerve Grading Scale 2.0. The results
      were analyzed according to patient age, follow-up duration, and the use of
      postoperative radiation therapy. RESULTS: Among the 12 patients who were
      evaluated, the mean follow-up duration was 21.8 months, the mean age at the time
      of surgery was 42.8 years, and the mean facial expression score was 14.6 points,
      indicating moderate dysfunction. Facial expression scores were not influenced by
      age at the time of surgery, follow-up duration, or the use of postoperative
      radiation therapy. CONCLUSIONS: The results of this study indicate that facial
      nerve cable grafting using the sural nerve can restore facial expression.
      Although patients were provided with appropriate treatment, the survival rate for
      salivary gland cancer was poor. We conclude that immediate facial nerve
      reconstruction is a worthwhile procedure that improves quality of life by
      allowing the recovery of facial expression, even in patients who are older or may
      require radiation therapy.

PMID- 26217568
TI  - Correction of Sunken Upper Eyelids by Anchoring the Central Fat Pad to the Medial
      Fat Pad during Upper Blepharoplasty.
AB  - BACKGROUND: Many methods have been proposed for the correction of sunken upper
      eyelids. These methods include surgical treatments, such as micro-fat, dermofat,
      or fascia-fat grafts, or the use of alloplastic materials. Here, we present our
      experience of sunken upper eyelid correction involving the simple addition of
      anchoring the central fat pad to the medial fat pad during upper blepharoplasty.
      METHODS: We performed 74 cases of upper blepharoplasty with sunken upper eyelid
      correction between October 2013 and September 2014. The lateral portion of the
      central fat pad was partially dissected to facilitate anchoring. The medial fat
      pad was gently exposed and then pulled out to facilitate anchoring. After the
      rotation of the dissected lateral portion of the central fat pad by 180 degrees 
      to the medial side, it was anchored spreading to the medial fat pad. Photographs
      taken at 6 months postoperatively were presented to three physicians for
      objective assessment. Of the 74 patients, 54 patients followed at 6 months
      postoperatively were included in this retrospective, objective assessment.
      RESULTS: Sunken eyelids were effectively corrected in 51 of the 54 patients, but
      3 had minimal effect because preaponeurotic fat pads had been removed during
      previous upper blepharoplasty. In addition to correcting sunken eyelids, lateral
      bulging was corrected and a better definition of the lateral portion of upper lid
      creases was obtained. CONCLUSIONS: Anchoring the central fat pad to the medial
      fat pad provides an effective means of correcting sunken upper eyelids during
      upper blepharoplasty.

PMID- 26217569
TI  - Malignant Melanoma Arising in Red Tattoo Ink.
AB  - We report the case of a 33-year-old male who presented with a malignant melanoma
      on his anterior chest wall. The lesion was only found in the red ink pigment of
      the tattoo, as were several in-transit dermal metastases. Possible explanations
      include a pre-existing lesion which was seeded with red ink or the possibility of
      the red ink causing an inflammatory reaction leading to malignant transformation.
      This is the first reported case of a melanoma developing in the red ink pigment
      of a multi-colored tattoo. 

PMID- 26217570
TI  - Potential Use of Transferred Lymph Nodes as Metastasis Detectors after Tumor
      Excision.
AB  - Due to the fact that it reliably results in positive outcomes, lymph node flap
      transfer is becoming an increasingly popular surgical procedure for the
      prevention and treatment of lymphedema. This technique has been shown to
      stimulate lymphoangiogenesis and restore lymphatic function, as well as
      decreasing infection rates, minimizing pain, and preventing the recurrence of
      lymphedema. In this article, we investigate possible additional benefits of lymph
      node flap transfer, primarily the possibility that sentinel lymph nodes may be
      used to detect micro-metastasis or in-transit metastasis and may function as an
      additional lymphatic station after the excision of advanced skin cancer. 

PMID- 26217571
TI  - A Cystic Mass in the Popliteal Fossa and Its Differential Diagnosis.

PMID- 26217572
TI  - Bimodal Treatment of a Huge Hypervascular Neurofibroma on the Groin.

PMID- 26217573
TI  - Giant Extrapleural Solitary Fibrous Tumor of the Thigh.

PMID- 26217574
TI  - Management of Foreign Object Migration and Surgical Removal with C-Arm
      Fluoroscopy.

PMID- 26217575
TI  - Innervated Free Groin Flap.

PMID- 26217576
TI  - The Role of the Plastic Surgeon in Sentinel Lymph Node Biopsy of Internal Mammary
      Nodes.

PMID- 26217577
TI  - Bilateral Thoracodorsal Neuromas: A Cause of Persistent Breast Pain after
      Bilateral Latissimus Dorsi Breast Reconstruction.

PMID- 26217578
TI  - Rice Body Tenosynovitis without Tuberculosis Infection after Multiple Acupuncture
      Procedures in a Hand.

PMID- 26217579
TI  - Foreign-Body Granuloma after Metacarpal Fracture Treatment with Absorbable
      Implants.

PMID- 26217580
TI  - Spontaneous Iliopsoas Hematoma: A Rare Complication of Anticoagulant Use.

PMID- 26217581
TI  - Breast Reconstruction: Closing the Loop after Breast Cancer.

PMID- 26217582
TI  - Erratum: Clinical Application of Three-Dimensional Printing Technology in
      Craniofacial Plastic Surgery.
AB  - [This corrects the article on p. 267 in vol. 42, PMID: 26015880.]. 

PMID- 26217583
TI  - Immune Infiltration and Prostate Cancer.
AB  - It is becoming increasingly clear that inflammation influences prostate cancer
      (PCa) development and that immune cells are among the primary drivers of this
      effect. This information has launched numerous clinical trials testing
      immunotherapy drugs in PCa patients. The results of these studies are promising
      but have yet to generate a complete response. Importantly, the precise immune
      profile that determines clinical outcome remains unresolved. Individual immune
      cell types are divided into various functional subsets whose effects on tumor
      development may differ depending on their particular phenotype and functional
      status, which is often shaped by the tumor microenvironment. Thus, this review
      aims to examine the current knowledge regarding the role of inflammation and
      specific immune cell types in mediating PCa progression to assist in directing
      and optimizing immunotherapy targets, regimens, and responses and to uncover
      areas in which further research is needed. Finally, a summary of ongoing
      immunotherapy clinical trials in PCa is provided. 

PMID- 26217585
TI  - Modeling Combined Chemotherapy and Particle Therapy for Locally Advanced
      Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma is the only cancer for which deaths are
      predicted to increase in 2014 and beyond. Combined radiochemotherapy protocols
      using gemcitabine and hypofractionated X-rays are ongoing in several clinical
      trials. Recent results indicate that charged particle therapy substantially
      increases local control of resectable and unresectable pancreas cancer, as
      predicted from previous radiobiology studies considering the high tumor hypoxia.
      Combination with chemotherapy improves the overall survival (OS). We compared
      published data on X-ray and charged particle clinical results with or without
      adjuvant chemotherapy calculating the biological effective dose. We show that
      chemoradiotherapy with protons or carbon ions results in 1 year OS significantly
      higher than those obtained with other treatment schedules. Further
      hypofractionation using charged particles may result in improved local control
      and survival. A comparative clinical trial using the standard X-ray scheme vs.
      the best current standard with carbon ions is crucial and may open new
      opportunities for this deadly disease. 

PMID- 26217584
TI  - Understanding the Key to Targeting the IGF Axis in Cancer: A Biomarker
      Assessment.
AB  - Type 1 insulin like growth factor receptor (IGF-1R) targeted therapies showed
      compelling pre-clinical evidence; however, to date, this has failed to translate
      into patient benefit in Phase 2/3 trials in unselected patients. This was further
      complicated by the toxicity, including hyperglycemia, which largely results from
      the overlap between IGF and insulin signaling systems and associated feedback
      mechanisms. This has halted the clinical development of inhibitors targeting IGF
      signaling, which has limited the availability of biopsy samples for correlative
      studies to understand biomarkers of response. Indeed, a major factor contributing
      to lack of clinical benefit of IGF targeting agents has been difficulty in
      identifying patients with tumors driven by IGF signaling due to the lack of
      predictive biomarkers. In this review, we will describe the IGF system, rationale
      for targeting IGF signaling, the potential liabilities of targeting strategies,
      and potential biomarkers that may improve success. 

PMID- 26217586
TI  - Range Verification Methods in Particle Therapy: Underlying Physics and Monte
      Carlo Modeling.
AB  - Hadron therapy allows for highly conformal dose distributions and better sparing
      of organs-at-risk, thanks to the characteristic dose deposition as function of
      depth. However, the quality of hadron therapy treatments is closely connected
      with the ability to predict and achieve a given beam range in the patient.
      Currently, uncertainties in particle range lead to the employment of safety
      margins, at the expense of treatment quality. Much research in particle therapy
      is therefore aimed at developing methods to verify the particle range in
      patients. Non-invasive in vivo monitoring of the particle range can be performed
      by detecting secondary radiation, emitted from the patient as a result of nuclear
      interactions of charged hadrons with tissue, including beta (+) emitters, prompt
      photons, and charged fragments. The correctness of the dose delivery can be
      verified by comparing measured and pre-calculated distributions of the secondary
      particles. The reliability of Monte Carlo (MC) predictions is a key issue.
      Correctly modeling the production of secondaries is a non-trivial task, because
      it involves nuclear physics interactions at energies, where no rigorous theories
      exist to describe them. The goal of this review is to provide a comprehensive
      overview of various aspects in modeling the physics processes for range
      verification with secondary particles produced in proton, carbon, and heavier ion
      irradiation. We discuss electromagnetic and nuclear interactions of charged
      hadrons in matter, which is followed by a summary of some widely used MC codes in
      hadron therapy. Then, we describe selected examples of how these codes have been
      validated and used in three range verification techniques: PET, prompt gamma, and
      charged particle detection. We include research studies and clinically applied
      methods. For each of the techniques, we point out advantages and disadvantages,
      as well as clinical challenges still to be addressed, focusing on MC simulation
      aspects. 

PMID- 26217587
TI  - Melanoma: From Incurable Beast to a Curable Bet. The Success of Immunotherapy.
AB  - After Coley's observation in 1891 of tumor regression in a patient who developed
      a postoperative infection, the field of immunotherapy is finally reborn. Avoiding
      immune destruction is now considered a hallmark of cancer, and the immunotherapy
      arena has exploded with the recent advances demonstrating an improvement in
      survival and a durability of response in patients with different cancer types,
      which translates into improved overall survival benefit. Here, we provide an
      overview of the main immune-oncology treatment strategies that, either alone or
      in combination, are undergoing clinical development. Namely, we will refer to
      those immunotherapeutic strategies that include adoptive transfer of ex vivo
      activated T cells, immunomodulatory monoclonal antibodies, and cancer vaccines.
      Our major focus will be to describe these approaches in melanoma, a cancer type
      transformed by immunotherapy into a potentially curable disease. 

PMID- 26217590
TI  - Retraction.
AB  - [This retracts the article DOI: 10.7860/JCDR/2014/8462.4679.]. 

PMID- 26217591
TI  - Retraction.
AB  - [This retracts the article DOI: 10.7860/JCDR/2013/4833.2724.]. 

PMID- 26217589
TI  - Identification and characterization of three Vibrio alginolyticus non-coding RNAs
      involved in adhesion, chemotaxis, and motility processes.
AB  - The capability of Vibrio alginolyticus to adhere to fish mucus is a key virulence
      factor of the bacteria. Our previous research showed that stress conditions, such
      as Cu(2+), Pb(2+), Hg(2+), and low pH, can reduce this adhesion ability. Non
      coding (nc) RNAs play a crucial role in regulating bacterial gene expression,
      affecting the bacteria's pathogenicity. To investigate the mechanism(s)
      underlying the decline in adhesion ability caused by stressors, we combined high
      throughput sequencing with computational techniques to detect stressed ncRNA
      dynamics. These approaches yielded three commonly altered ncRNAs that are
      predicted to regulate the bacterial chemotaxis pathway, which plays a key role in
      the adhesion process of bacteria. We hypothesized they play a key role in the
      adhesion process of V. alginolyticus. In this study, we validated the effects of
      these three ncRNAs on their predicted target genes and their role in the V.
      alginolyticus adhesion process with RNA interference (i), quantitative real-time
      polymerase chain reaction (qPCR), northern blot, capillary assay, and in vitro
      adhesion assays. The expression of these ncRNAs and their predicted target genes
      were confirmed by qPCR and northern blot, which reinforced the reliability of the
      sequencing data and the target prediction. Overexpression of these ncRNAs was
      capable of reducing the chemotactic and adhesion ability of V. alginolyticus, and
      the expression levels of their target genes were also significantly reduced. Our
      results indicated that these three ncRNAs: (1) are able to regulate the bacterial
      chemotaxis pathway, and (2) play a key role in the adhesion process of V.
      alginolyticus. 

PMID- 26217593
TI  - Correction.
AB  - [This corrects the article DOI: 10.7860/JCDR/2014/8236.5162.]. 

PMID- 26217592
TI  - Correction.
AB  - [This corrects the article DOI: 10.7860/JCDR/2013/5702.3485.]. 

PMID- 26217594
TI  - Correction.
AB  - [This corrects the article DOI: 10.7860/JCDR/2014/8024.4021.]. 

PMID- 26217588
TI  - Immunosuppressive Mechanisms of Malignant Gliomas: Parallels at Non-CNS Sites.
AB  - The central nervous system (CNS) possesses powerful local and global
      immunosuppressive capabilities that modulate unwanted inflammatory reactions in
      nervous tissue. These same immune-modulatory mechanisms are also co-opted by
      malignant brain tumors and pose a formidable challenge to brain tumor
      immunotherapy. Routes by which malignant gliomas coordinate immunosuppression
      include the mechanical and functional barriers of the CNS; immunosuppressive
      cytokines and catabolites; immune checkpoint molecules; tumor-infiltrating immune
      cells; and suppressor immune cells. The challenges to overcoming tumor-induced
      immunosuppression, however, are not unique to the brain, and several analogous
      immunosuppressive mechanisms also exist for primary tumors outside of the CNS.
      Ultimately, the immune responses in the CNS are linked and complementary to
      immune processes in the periphery, and advances in tumor immunotherapy in
      peripheral sites may therefore illuminate novel approaches to brain tumor
      immunotherapy, and vice versa. 

PMID- 26217595
TI  - Explore the dynamic alternation of gene PLAC4 mRNA expression levels in maternal
      plasma in second trimester for nonivasive detection of trisomy 21.
AB  - OBJECTIVE: Noninvasive prenatal detection of trisomy 21 (T21) has been achieved
      by measuring the ratio of two alleles of a single nucleotide polymorphism in
      circulating placenta specific 4 (PLAC4) mRNA in maternal plasma with a few assays
      in recent years. Our research is to explore the variations of PLAC4 mRNA
      expression level in maternal plasma with normal pregnancies in second trimester,
      which can provide pregnant women deeper insights with suitable detection period
      for the non-invasive prenatal detection of T21. METHODS: We measured a serial
      plasma PLAC4 mRNA concentrations weekly from the same 25 singleton normal
      pregnant women. We recruited maternal plasma samples from 45 singleton pregnant
      women, comprising of 25 euploid pregnancies (control group; range, 17 to 21
      weeks) and 20 T21 pregnancies (T21 group; range, 19 to 24 weeks). With the
      application of reverse transcription polymerase chain reaction, we achieved an
      insight of PLAC4 mRNA expression levels in maternal plasma during second
      trimester with euploid pregnancies. RESULTS: Among the control group, the levels
      of PLAC4 mRNA expression in the gestation of 17 to 18 weeks were significantly
      less than those in the gestation of 18 to 21 weeks (P<0.05). The average PLAC4
      mRNA concentration of the normal pregnant women was not higher than that of the
      T21 group (P>0.05). CONCLUSION: The PLAC4 mRNA showed a higher level of
      expression in the gestation of 18 to 21 weeks with an euploid pregnancy of
      pregnant women. We also found that there was no significant difference in plasma
      PLAC4 mRNA concentration between the normal and the T21 pregnancies in second
      trimester.

PMID- 26217596
TI  - Feasibility of three-dimensional reconstruction and automated measurement of
      fetal long bones using 5D Long Bone.
AB  - OBJECTIVE: To evaluate the feasibility of five-dimensional Long Bone (5D LB), a
      new technique that automatically archives, reconstructs images, and measures
      lengths of fetal long bones, to assess whether the direction of volume sweep
      influences fetal long bone measurements in three-dimensional (3D) ultrasound and
      5D LB, and to compare measurements of fetal long bone lengths obtained with 5D LB
      and those obtained with conventional two-dimensional (2D) and manual 3D
      techniques. METHODS: This prospective study included 39 singleton pregnancies at
      26+0 to 32+0 weeks of gestation. Multiple pregnancies, fetuses with multiple
      congenital anomalies, and mothers with underlying medical diseases were excluded.
      Fetal long bones of the lower extremities-the femur, tibia, and fibula were
      measured by 2D and 3D ultrasound, and 5D LB, by an expert and non-expert
      examiner. First, we analyzed the 3D ultrasound and 5D LB data according to 2
      different sweeping angles. We analyzed intra- and inter-observer variability and
      agreement between ultrasound techniques. Paired t-test, interclass correlation
      coefficient, and Bland-Altman plot and Passing-Bablok regression were used for
      statistical analysis. RESULTS: There was no statistical difference between long
      bone measurements analyzed according to 2 different volume-sweeping angles by 3D
      ultrasound and 5D LB. Intra- and inter-observer variability were not
      significantly different among all 3 ultrasound techniques. Comparing 2D
      ultrasound and 5D LB, the interclass correlation coefficient for femur, tibia,
      and fibula was 0.91, 0.92, and 0.89, respectively. CONCLUSION: 5D LB is
      reproducible and comparable with conventional 2D and 3D ultrasound techniques for
      fetal long bone measurement.

PMID- 26217597
TI  - Role of surgical therapy in the management of gestational trophoblastic
      neoplasia.
AB  - OBJECTIVE: To evaluate the role of adjuvant surgical procedures in the management
      of gestational trophoblastic neoplasia (GTN). METHODS: In a retrospective review
      of medical records at the Severance Hospital, we identified 174 patients
      diagnosed with GTN between 1986 and 2006. Of the 174 patients, 129 (74%) were
      assigned to the nonmetastatic group, and 45 (26%) to the metastatic group; of the
      metastatic group patients, 6 were in the low-risk group and 39 were in the high
      risk group. Thirty-two patients underwent 35 surgical procedures as part of the
      GTN treatment. The procedures included hysterectomy, lung resection, craniotomy,
      uterine wedge resection, uterine suturing for bleeding, salpingo-oophorectomy,
      pretherapy dilatation and curettage, adrenalectomy, nephrectomy, and uterine
      artery embolization. RESULTS: Of the 32 patients who underwent surgical
      procedures, 28 (87%) survived. Eleven patients underwent surgery for
      chemoresistant disease after receiving one or more chemotherapy regimens. Twelve
      patients underwent procedures to control tumor hemorrhage. Nine (81%) of 11
      patients with chemoresistant disease survived, and 8 patients who underwent
      salvage surgery for chemoresistant disease received further chemotherapy. Of 21
      patients who underwent hysterectomy, 19 (90%) achieved remission. All of three
      patients who had resistant foci of choriocarcinoma in the lung achieved remission
      through pulmonary resection. CONCLUSION: Adjuvant surgical procedures, especially
      hysterectomy and pulmonary resection for chemoresistant disease, as well as
      procedures to control hemorrhage, are pivotal in the management of GTN.

PMID- 26217598
TI  - Public perception of risk-reducing salpingectomy for preventing ovarian cancer.
AB  - OBJECTIVE: The fallopian tube is considered as the site of origin of serous
      ovarian cancer, and risk-reducing salpingectomy (RRS) has been proposed as a new
      and safe strategy for preventing ovarian cancer. However, little is known about
      the public perception of RRS. METHODS: We performed a questionnaire survey of 100
      healthy female volunteers in November 2014. Questionnaire for this survey
      included questions on demographics, medical history, knowledge of and belief
      about RRS, and barrier to its application. RESULTS: Among 100 respondents, 71%
      did not realize the seriousness of ovarian cancer, 79% were unaware of the fact
      that salpinx was the origin of ovarian cancer, and 87% stated that they had never
      heard of RRS as a preventive method for ovarian cancer. Also, 98% of respondents
      replied that they had the right to be informed about RRS and the choice given.
      The respondents' fears about RRS included increased risk of surgical
      complications (68%), no benefit (8%), and increased surgical costs (3%).
      CONCLUSION: Most general women were unaware of RRS as a method for preventing
      ovarian cancer in women at average risk. Therefore, physicians should discuss RRS
      with patients and consider this procedure at the time of abdominal or pelvic
      surgery.

PMID- 26217599
TI  - Public perception of "scarless" laparoendoscopic single-site surgery in
      gynecology.
AB  - OBJECTIVE: To investigate the public perception of laparoendoscopic single-site
      surgery (LESS) according to the age group. METHODS: An anonymous questionnaire
      about the desire for cosmesis and the preference for LESS in treatment of benign
      gynecologic diseases was provided to healthy volunteers (n=102). The survey
      participants were divided into two age groups (young women <=40 years and middle
      aged women >40 years). The desire for cosmesis was assessed using a validated
      scale, Body Image Scale. RESULTS: All of the participants completed the
      questionnaire. The Body Image Scale scores were not different between the two age
      groups (11.5+/-3.5 vs. 11.8+/-4.0, P=0.656). The most common fear of surgery was
      the risk of complications in both age groups (69% in the young age group and 65%
      in the middle-aged group). Unless the operative risk increased, most of the
      participants (61% to 67%) in both age groups preferred LESS. Their choice was
      influenced by reduced scarring (43% to 61%), more safety (20% to 39%), reduced
      postoperative pain (8% to 10%), and new technology (4% to 6%). CONCLUSION: Based
      on these results, there was no difference in the desire for cosmesis and
      perception of LESS according to the age. Therefore, physicians should discuss and
      consider LESS even in middle-aged women.

PMID- 26217600
TI  - Laparoendoscopic single-site versus conventional laparoscopic surgery for ovarian
      mature cystic teratoma.
AB  - OBJECTIVE: To compare the intraoperative and postoperative outcomes of
      laparoendoscopic single-site surgery (LESS) versus conventional laparoscopic
      surgery in women with ovarian mature cystic teratoma. METHODS: A retrospective
      review of 303 women who underwent LESS (n=139) or conventional laparoscopic
      surgery (n=164) due to ovarian mature cystic teratoma was performed. Intra- and
      postoperative outcomes were compared between the two groups. RESULTS: There was
      no intergroup difference in age, body weight, height, body mass index,
      comorbidities, tumor size, bilaterality of tumor, or the type of surgery.
      However, more patients in the LESS group had a history of previous abdominal
      surgery (19.4% vs. 6.7%, P=0.001). Surgical outcomes including operating time (89
      vs. 87.8 minutes, P=0.734), estimated blood loss (69.4 vs. 68.4 mL, P=0.842),
      transfusion requirement (2.2% vs. 0.6%, P=0.336), perioperative hemoglobin level
      change (1.3 vs. 1.2 g/dL, P=0.593), postoperative hospital stay (2.0 vs. 2.1
      days, P=0.119), and complication rate (1.4% vs. 1.8%, P=0.999) did not differ
      between LESS and conventional groups. Postoperative pain scores measured using a
      visual analogue scale were significantly lower in the LESS group at 8 hours
      (P=0.021), 16 hours (P=0.034), and 32 hours (P=0.004) after surgery, and 32 of
      139 patients (23%) in the LESS group and 78 of 164 patients (47.6%) in the
      conventional group required at least one additional analgesic (P<0.001).
      CONCLUSION: LESS was feasible and showed comparable surgical outcomes with
      conventional laparoscopic surgery for women with ovarian mature cystic teratoma.
      LESS was associated with less postoperative pain and required less analgesia.

PMID- 26217601
TI  - Dose-response relationship between cigarette smoking and female sexual
      dysfunction.
AB  - OBJECTIVE: To evaluate whether smoking is a risk factor for female sexual
      dysfunction (FSD) and to determine the relationship between the cumulative
      smoking dose and FSD in premenopausal women. METHODS: The study population
      consisted of sexually active premenopausal women. The frequency of FSD and female
      sexual function index (FSFI) total score were evaluated according to the smoking
      status (never/former and current smokers). Evaluation of sexual function was done
      using FSFI questionnaire, and women with FSFI score of <=26.55 were considered to
      have FSD. In current smokers, sexual function was also evaluated according to the
      cumulative smoking dose and nicotine dependency. RESULTS: A total of 900 women
      were included, and the frequency of current smokers and the frequency of FSD were
      62 (6.9%) and 496 (55.1%), respectively. In current smokers, the frequency of FSD
      was significantly higher and the median total FSFI score was significantly lower
      than in never/former smokers, and this difference of FSD remained significant
      after adjustment for confounding variables. Among current smokers, the cumulative
      smoking dose (pack-years) and the total FSFI score showed negative correlation,
      in which increased cumulative smoking dose was associated with lower total FSFI
      score (r=-0.278, P<0.05). In terms of nicotine dependency, the total FSFI score
      of moderately to heavily nicotine dependent smokers was significantly lower than
      that of lightly dependent smokers. CONCLUSION: In premenopausal women, current
      smoking was an independent risk factor for FSD. And cumulative smoking dose and
      nicotine dependency were associated with higher risk of FSD.

PMID- 26217602
TI  - Hyperplastic primary vitreous with hemorrhage manifested as a hyperechoic mass in
      the fetal orbit by prenatal ultrasound in a case of isolated unilateral
      microphthalmia.
AB  - Congenital microphthalmia is a rare anomaly of the fetal orbit resulting from
      developmental defects of the primary optic vesicle. Chromosomal anomalies,
      genetic defect, infection, and prenatal drug exposure are the most common causes.
      Congenital microphthalmia is usually associated with other abnormalities, and
      cases of isolated microphthalmia are rarely reported. Congenital microphthalmia
      can be diagnosed by prenatal ultrasound by measuring the axial diameter of the
      eye ball, but the accuracy depends on fetal position and associated anomalies. We
      report a case of an isolated unilateral microphthalmia which was not diagnosed by
      prenatal ultrasound, because the only abnormal prenatal ultrasound finding was a
      small hyperechoic mass lesion in the eye ball and the subsequent scan of the
      orbits was limited due to fetal prone position. The hyperechoic mass lesion in
      the eye ball was finally diagnosed as a persistent hyperplastic primary vitreous
      with hemorrhage by neonatal magnetic resonance image. 

PMID- 26217603
TI  - Single-port laparoscopic debulking surgery of variant benign metastatic
      leiomyomatosis with simultaneous lymphatic spreading and intraperitoneal seeding.
AB  - Benign metastatic leiomyomatosis (BML) is a rare disease characterized by smooth
      muscle cell proliferation in extrauterine sites including the lung, abdomen,
      pelvis, and retroperitoneum. Depending on location, BML is classified as
      intravenous leiomyomatosis and diffuse peritoneal leiomyomatosis. Pathogenesis of
      BML can be iatrogenic after previous myomectomy or hysterectomy, hormonal, or
      coelomic metaplasia. Treatment options are observation, hormonal suppression,
      and/or surgical debulking via laparotomy or laparoscopy. Laparoscopic surgery is
      gaining in popularity in the gynecologic field compared to laparotomic surgery
      and single-port laparoscopy has the benefits of cosmesis and early tissue
      extraction by transumbilical morcellation. We report a 39-year-old woman with BML
      who underwent single-port laparoscopy debulking surgery. 

PMID- 26217604
TI  - A rare case of post-hysterectomy vault site iatrogenic endometriosis.
AB  - A 45-year-old woman with a prior history of hysterectomy due to adenomyosis and
      leiomyomas was presented at our outpatient gynecology clinic 13 months later with
      sudden lower pelvic discomfort and vaginal bleeding symptoms. The patient
      underwent vaginal vault biopsy however diagnosis was still uncertain. Additional
      evaluation was required due to massive rebleeding incidents. After an emergent
      explorative laparoscopic operation with total excision of the vault, a diagnosis
      of vaginal vault endometriosis was made. Our theory is that a possible
      transplantation of endometrial cells during morcellation of the adenomyotic
      uterus which then may have progressed to iatrogenic endometriosis of the vaginal
      vault. Therefore, vault endometriosis must be considered in incidences of delayed
      massive bleeding occurring in post-hysterectomy patients when other diagnoses
      have been excluded. 

PMID- 26217605
TI  - Pelvic Castleman's disease presenting as an adnexal tumor in a young woman.
AB  - Castleman's disease (CD) is a rare benign disorder of unknown etiology
      characterized by proliferation of lymphoid tissues. Seventy percent of this tumor
      occurs in the mediastinum and it is seldom found in neck, pancreas or pelvis. We
      report a case of asymptomatic pelvic CD initially presenting as an adnexal tumor
      in a 27-year-old woman. Initial transvaginal sonography revealed 7-cm-sized
      hyperechoic mass adjacent to the right ovary and the following abdominal computed
      tomography scanning showed the same sized mass located on the right
      extraperitoneal pelvic cavity. Laparoscopic mass excision was performed without
      any complication and pathological diagnosis was made as CD. CD should be included
      in the differential diagnosis of female pelvic masses which are noted in the
      pelvic cavity. In this report, we review the clinicopathological findings in a
      presentation of CD. 

PMID- 26217606
TI  - Tamoxifen-associated polypoid endometriosis mimicking an ovarian neoplasm.
AB  - Tamoxifen has been widely used for adjuvant treatment of breast cancer, but
      several gynecological side effects have been noted, including endometrial
      hyperplasia, polyp and carcinoma. Polypoid endometriosis is one of the extremely
      rare benign complications associated with tamoxifen therapy. A 66-year-old
      postmenopausal woman, who had received left partial mastectomy due to breast
      cancer (about 4 years ago) and was taking tamoxifen treatment, had an ovarian
      cyst on ultrasonography. Pelvic magnetic resonance imaging suggested tamoxifen
      associated endometrial and ovarian changes, especially a 4.1*3.4-cm-sized, well
      defined, multicystic mass in the right ovary. She received hysterectomy with
      bilateral salpingo-oophorectomy. Microscopically, the right paratubal mass showed
      endometrial glands and stroma, and immunohistochemical staining for CD10
      confirmed the endometrial nature of the stroma. Three cases of polypoid
      endometriosis have been reported in the Korean literature, but in none of the
      cases, polypoid endometriosis was associated with tamoxifen use. Herein, we
      report the first case of polypoid endometriosis associated with tamoxifen
      treatment in Korea. 

PMID- 26217607
TI  - Comment on: Endometrial cancer occurrence five years after breast cancer in BRCA2
      mutation patient.

PMID- 26217608
TI  - Ruptured Abdominal Aortic Aneurysm with Antecedent Endovascular Repair of
      Abdominal Aortic Aneurysm.
AB  - Late aortic rupture following successful endovascular repair of abdominal aortic
      aneurysm still does occur. It represents the ultimate failure of endovascular
      aortic repair of abdominal aortic aneurysm (EVAR) and subjects patients to
      equivalent risk of death as de novo rupture. Unfortunately, it is difficult to
      identify patients at risk for post-EVAR rupture as many present with aortic
      rupture in the absence of any endograft-related complications. Continued
      surveillance and timely intervention are of paramount importance to assure
      rupture-free survival, the ultimate goal of any aneurysm treatment modality. The
      vascular surgeon needs to be prepared to provide the optimal therapy, whether
      open or endovascular, for this challenging cohort of patients. 

PMID- 26217609
TI  - Different Responses of Neointimal Cells to Imatinib Mesylate and Rapamycin
      Compared with Normal Vascular Smooth Muscle Cells.
AB  - PURPOSE: This study was designed to investigate whether vascular smooth muscle
      cells (VSMC) from the neointima showed any different response to anti
      proliferative agents, such as rapamycin or imatinib mesylate, compared to VSMCs
      from normal artery. MATERIALS AND METHODS: Intimal hyperplasia was made by
      carotid balloon in jury in male rats. Neointimal cells at 4 weeks after injury
      and normal VSMCs were extracted by enzymatic isolation method and cultured. Cell
      viability and proliferation were tested in VSMCs from injured left carotid artery
      and uninjured right carotid artery. Tests were repeated with rapamycin, imatinib
      mesylate or both in various concentrations. RESULTS: Rapamycin decreased cell
      viability only at a high concentration of 10(-5) M in uninjured VSMCs. Combined
      drugs decreased cell viability at a lower concentration of 10(-7) M in uninjured
      VSMCs, and at a higher concentration of 10(-5) M in neointimal cells. Overall,
      rapamycin showed cytocidal effects at a high concentration of 10(-5) M, whereas
      imatinib did not. Cell proliferation of neointima was significantly decreased
      along with the drug concentration. Cell proliferation of uninjured VSMCs was
      significantly decreased at higher drug concentrations. Combined drug therapy
      showed synergistic effects. Overall, neointimal cells are more susceptible to the
      antiproliferative effects of the drugs. CONCLUSION: Neointimal cells from the
      injured carotid artery are more susceptible to the antiproliferative effect of
      imatinib and rapamycin. Both drugs can be a used for the prevention of intimal
      hyperplasia, which could be investigated through further in vivo studies.

PMID- 26217610
TI  - Tracking the Fate of Muscle-derived Stem Cells: an Insight into the Distribution
      and Mode of Action.
AB  - PURPOSE: To examine the fate of muscle-derived stem cells (MDSC) after injection
      into different host conditions and provide an insight for their mechanism of
      action. MATERIALS AND METHODS: MDSCs differentiated in vitro towards the
      endothelial lineage and transfected with lentivirus tagged with green fluorescent
      protein (GFP) were injected into two animal models mimicking vascular diseases:
      hindlimb ischemia and carotid injury models. Injected cells were tracked at the
      site of injection and in remote organs by harvesting the respective tissues at
      different time intervals and performing immunofluorescent histological analyses.
      Stem cell survival was quantified at the site of injection for up to 4 weeks.
      RESULTS: MDSCs were successfully tagged with fluorescent material GFP and showed
      successful implantation into the respective injection sites. These cells showed a
      higher affinity to implant in blood vessel walls as shown by double fluorescent
      co-stain with CD31. Quantification of stem cell survival showed a timede pendent
      decrease from day 3 to 4 weeks (survival rate normalized against day 3 was 72.0%
      at 1 week, 26.8% at 2 weeks and 2.4% at 4 weeks). Stem cells were also found in
      distant organs, especially the kidneys and liver, which survived up to 4 weeks.
      CONCLUSION: MDSCs were successfully tracked in different vascular disease models,
      and their fate was assessed in terms of cell survival and distribution. Better
      understanding of the donor cell properties, including their interaction with the
      host conditions and their mechanism of action, are needed to enhance cell
      survival and achieve improved outcomes.

PMID- 26217611
TI  - Experiences of Surgical Treatment for Juxtarenal Aortic Occlusion.
AB  - PURPOSE: To evaluate the outcomes of juxtarenal aortic occlusion (JRAO), a review
      of 15 patients who underwent aortic bypass replacement following aortorenal
      thrombectomy, especially focusing on the safety of suprarenal aortic clamping or
      transient aortic compression, was undertaken. MATERIALS AND METHODS: During the
      period of June 2001 to November 2012, 15 patients with JRAO (chronic 10, acute 5)
      were analyzed retrospectively. JRAO with combined stenosis of the renal artery
      was found in 2 patients, renal artery thrombus in 8 patients, and normal in 5
      patients. RESULTS: All patients were males. Mean age was 61.7+/-11.2 years. There
      were 14 aortobifemoral bypass grafting and 1 aortobiiliac bypass grafting. Six
      Dacron and 9 PTFE artificial Y-grafts were implanted to the aorta with end-to-end
      anastomosis in the proximal aorta. Suprarenal aortic clamping was performed in 7
      patients, supraceliac clamping in 2 patients, and transient aortic compression in
      6 patients. There were 13 cases with aortic clamping time <10 minutes and 2 cases
      with >10 minutes. Thrombectomy of the aorta and renal artery was performed in 10
      (66.7%) patients. There were no operative mortality cases. The perioperative
      morbidity rate was 26.7% (4/15). Preoperative renal function was impaired in four
      patients. The renal functions of these cases were recovered postoperatively.
      CONCLUSION: Aortic bypass replacement following aortorenal thrombectomy with
      suprarenal aortic clamping or transient aortic compression for JRAO is the
      optimal treatment. It is important to focus on short renal ischemic time during
      suprarenal aortic clamping for prevention of renal damage. It provides unmatched
      perioperative and long-term results.

PMID- 26217612
TI  - Analysis of Intermediate Term Results of Short Vein Bypass Graft in the Patient
      with Critical Limb Ischemia.
AB  - PURPOSE: Since the introduction of short vein bypass (SVB), many have reported
      its feasibility when long vein bypass (LVB) cannot be performed due to limited
      vein conduit. However, the presence of inflow-vessel disease may affect graft
      patency and thus require endovascular treatment prior to surgery. Our study aims
      to analyze the results between SVB and LVB. MATERIALS AND METHODS: From 2009 to
      2013, 27 bypass procedures were reviewed retrospectively. Outcomes such as
      patency rate, postoperative ankle brachial index (ABI) and limb salvage rate
      between SVB and LVB were compared. Wound healing time and primary patency rate
      were analyzed and the former was also analyzed according to the respective
      angiosome and revascularization type. RESULTS: There were 11 males and 16 females
      and the mean age was 66.6+/-12.3 years. Twenty four patients had TransAtlantic
      Inter-Society Consensus (TASC) D and 3 patients had TASC C lesions below knee.
      The 1-year cumulative patency rate between SVB and LVB were 63% and 66%, P=0.627.
      The limb salvage rate (100% vs. 73%; P=0.280) and postoperative ABI (0.592 vs.
      0.508; P=0.620) were higher in the SVB group than in the LVB group, although the
      differences were not significant. There was no difference in wound healing time
      by angiosomal revascularization type. In situ vein graft showed higher patency
      rate than reversed greater saphenous vein (75% vs. 61%; P=0.00). CONCLUSION: The
      results of SVB were similar to those of LVB. SVB is feasible in the setting of
      limited conduit availability, in combination with endovascular treatment in the
      presence of proximal lesions.

PMID- 26217613
TI  - Successful Access Rate and Risk Factor of Vascular Access Surgery in Arm for
      Dialysis.
AB  - PURPOSE: Preservation of adequate vascular access is of vital importance for
      patients undergoing chronic dialysis in renal failure. The aim of this study is
      to evaluate the successful access rate and risk factors of arteriovenous fistula
      (AVF) in the arm for dialysis at a single center. MATERIALS AND METHODS: Patients
      undergoing vascular access operation between January 2006 and December 2011 were
      retrospectively identified. RESULTS: A total of 362 vascular access operations
      were performed. There were 338 autologous AVFs (93.4%) and 24 prosthetic grafts
      (6.6%). Men comprised 58.3% of all subjects. Mean age was 59.5+/-14.7 years.
      There were 187 diabetes mellitus patients (51.7%). There was a mean duration of
      70.3+/-21.1 days between access creation to first cannulation. Overall successful
      access rate for dialysis was 95.9%. Of 338 autologous AVFs, 326 patients had
      patent AVFs for dialysis (96.4% surgical success rate), while 21 of 24 prosthetic
      grafts were patent (87.5% surgical success rate). A total of 141 patients (38.9%)
      came to surgery with preoperative central venous catheters (CVC) of which 130
      (35.9%) AVFs had a patent fistula in the arm. The only risk factor related to
      successful access rate of AVF was preoperative CVC placement (P=0.012).
      CONCLUSION: Successful vascular access rate was 95.9%. The only risk factor
      related to patent access of AVF was preoperative CVC placement. At least 6 months
      prior to expected dialysis, AVF surgery is recommended, which may overcome the
      challenge of co-morbid conditions from having a preoperative CVC.

PMID- 26217615
TI  - Thirty Year-Old Korean Society for Vascular Surgery: Challenging Issues to
      Overcome.

PMID- 26217614
TI  - Use of Reversed Iliac Leg Stent-Graft for the Treatment of Isolated Aneurysm of
      Internal Iliac Artery.
AB  - This is to report the technique of reversed iliac leg stent-graft in endovascular
      treatment for isolated internal iliac artery (IIA) aneurysm, which had
      significant size discrepancy between the common iliac artery (CIA) and external
      iliac artery (EIA) in 3 patients from different hospitals. Three patients were a
      85- and two 82-year-old men. Treated were right IIA aneurysms, sized 6.5*6.2 cm,
      5.0*4.0 cm, and 4.1 cm in longest diameter, respectively. The diameters of the
      right CIA and right EIA measured 21 mm/11 mm, 15 mm/11 mm, and 20 mm/10 mm,
      respectively. In all cases, reversed iliac leg stent-grafts were prepared on
      site; unsheathed and mounted upside-down manually, and deployed in each right
      CIA. Post-stent-graft angiograms showed complete exclusion of the aneurysms,
      except for minimal type 1 endoleak in one case. This technique is a useful
      treatment option in patients with isolated IIA aneurysm. 

PMID- 26217616
TI  - Occurrence and Prognosis of Symptomatic Venous Thromboembolism in Colorectal
      Cancer Surgery Patients.
AB  - PURPOSE: Colorectal cancer (CRC) has a high risk for postoperative thromboembolic
      complications such as venous thromboembolism (VTE) compared to other surgical
      diseases, but the relationship between VTE and CRC in Asian patients remains
      poorly understood. The present study examined the incidence of symptomatic VTE in
      Korean patients who underwent surgery for CRC. We also identified risk factors,
      incidence and survival rate for VTE in these patients. MATERIALS AND METHODS: The
      patients were identified from the CRC database treated from January 2011 to
      December 2012 in a single institution. These patients were classified into VTE
      and non-VTE groups, their demographic features were compared, and the factors
      which had significant effects on VTE and mortality between the two groups were
      analyzed. RESULTS: We analyzed retrospectively a total of 840 patients and the
      incidence of VTE was 3.7% (31 patients) during the follow-up period (mean, 17.2
      months). Histologic subtype (mucinous adenocarcinoma) and previous history of VTE
      affected the incidence of VTE on multivariate analysis. There was a statistically
      significant difference in survival rate between the VTE and non-VTE group, but
      VTE wasn't the factor affecting survival rate on multivariate analysis. Comparing
      differences in survival rate for each pathologic stage, there was only a
      significant difference in stage II patients. CONCLUSION: Among CRC patients after
      surgery, the incidence of VTE was approximately 3% within 1 year and development
      of VTE wasn't a significant risk factor for death in our study but these findings
      are not conclusive due to our small sample size.

PMID- 26217617
TI  - The Laterality of Deep Vein Thrombosis in the Pelvic and Lower Extremity Veins.
AB  - PURPOSE: This study aimed to determine whether deep vein thrombosis (DVT)
      predominantly occurred on a particular side in the pelvic and lower extremity
      veins. MATERIALS AND METHODS: Among 259 consecutive patients with leg swelling,
      65 were confirmed to have DVT in the pelvis and lower extremities, and enrolled
      in this study. The serum levels of initial D-dimer, antithrombin III, tissue
      plasminogen activator, factor VIII, proteins C and S, anticardiolipin antibodies
      immunoglobulin (Ig) G and IgM and lupus anticoagulant were measured and analyzed
      retrospectively. Lower extremity venous system was divided into 11 anatomic
      segments on each side, and thrombotic involvement in each segment was recorded to
      determine the laterality of thrombotic involvement for each patient. The presence
      of thrombus in a specific vein was assigned using a Thrombus Scoring System (TSS)
      score of 1. Predominant direction was determined based on the TSS score for each
      side. RESULTS: Left-side predominat DVT (57%) was most frequent. Patients with
      both-side equivalent DVT had the highest total TSS score (P=0.022). The
      predominant side was significantly different between men (right 44.1%) and women
      (left 74.2%) (P=0.022). Patients with both-side equivalent DVT had the highest
      mean age (69.3+/-9.9 years) as well as the highest mean levels of initial D-dimer
      (13.8+/-20.7 MUg/mL) and anticardiolipin antibody IgM (13.4+/-22.8 MPL)
      indicating increased coagulability. CONCLUSION: In the current study, left-side
      predominant DVT is most frequent in pelvis and lower extremities, and this
      phenomenon is more apparent in women. And both-side equivalent DVT is associated
      with the most advanced age and hypercoagulability.

PMID- 26217618
TI  - Central Transposition of the Cephalic Vein in Patients with Brachiocephalic
      Arteriovenous Fistula and Cephalic Arch Stenosis.
AB  - PURPOSE: Our study aims to evaluate to evaluate clinical outcomes after cephalic
      vein transposition (CVT) to the axilla in patients with brachiocephalic
      arteriovenous fistula (BC-AVF) and cephalic arch stenosis (CAS). MATERIALS AND
      METHODS: Hospital records of 13 patients (median age, 61 years; males, 54%) who
      received CVT to the proximal basilic/axillary vein due to either dysfunction
      (n=2) or thrombosis (n=11) between January 2010 and February 2014 were
      retrospectively reviewed. RESULTS: Operation was performed under local anesthesia
      in all cases. There was no technical failure. Concomitant inflow procedure
      (banding or aneurysmorrhaphy) was performed in 5 patients (38%). During follow-up
      (1 to 50 months, median 17 months), 3 patients died with functioning AVF and one
      was successfully transplanted. Two patients suffered from recurrent symptomatic
      stenosis of AVF and received percutaneous balloon angioplasty. Another 2 patients
      experienced AVF occlusion treated with interposition graft and manual
      fragmentation. Overall primary, assisted primary, and secondary patency rates
      were 77.5%, 92.3%, and 100% at 6 months and 66.1%, 92.3%, and 100% at 1 year,
      respectively. CONCLUSION: Although most patients presented with BC-AVF occlusion,
      technical success and access patency rates after CVT were favorable compared with
      historical data for interventional treatment. CVT should be considered as an
      appropriate option in selected patients with CAS.

PMID- 26217619
TI  - Hybrid Treatment of Coexisting Renal Artery Aneurysm and Abdominal Aortic
      Aneurysm in a Gallbladder Cancer Patient.
AB  - Renal artery aneurysm (RAA) is uncommon, and the coexistence of an abdominal
      aortic aneurysm (AAA) is an extremely rare condition with potentially high life
      threatening mortality in case of rupture. Aneurysms can be treated by
      endovascular intervention or open surgery. Although most of aneurysms are treated
      by endovascular intervention, open surgery is often necessary for RAAs associated
      with the proximal renal bifurcation or the branches in the distal renal arteries.
      We report a rare case of coexisting RAA with AAA treated by hybrid method,
      consisting of endovascular aneurysm repair for AAA and open surgery for RAA
      located adjacent to the distal branches of the renal artery. 

PMID- 26217620
TI  - In Situ Aortic Reconstruction with Femoral Vein after Post-EVAR Infection.
AB  - A 78-year-old male presented with early gastric cancer and a 5.5 cm-sized
      infrarenal abdominal aortic aneurysm, detected during regular screening.
      Endovascular aneurysm repair (EVAR) was performed first, followed by laparoscopic
      distal gastrectomy. After gastrectomy, the patient underwent computed tomography
      (CT) scan due to persistent fever, which showed increased perigraft fluid
      collection around the right iliac limb graft. Echocardiography also revealed
      mitral valve vegetation, consistent with infective endocarditis. Despite
      intensive antibiotic treatment, the patient had persistent fever and showed fluid
      extension to the psoas muscle on CT scan. On the 49th post operative day (POD)
      after EVAR, stent graft explantation and aortic reconstruction with the left
      superficial femoral vein was performed. Ligation of the right iliac artery for
      infection control and simultaneous femoro-femoral bypass was also performed. The
      patient was discharged on the 46th POD after graft removal without any events. 

PMID- 26217621
TI  - Open Repair of Ruptured Huge Aorto-Iliac Aneurysm: Warning of Colon Ischemia.
AB  - A giant abdominal aortic aneurysm (AAA) renders surgical treatment much more
      difficult by deforming the proximal infrarenal aortic neck (shortened length and
      disturbed angulation), by altering the iliac arteries (marked tortuosity and
      aneurysmal dilatation), and by displacing abdominal organs. Because the
      retroperitoneal rupture of giant AAA makes the mesentery more elongated and
      deformed, compromising its blood flow and thus increasing the risk of mesenteric
      ischemia such as colon ischemia. We describe here the surgical repair of a large
      infrarenal AAA with a ruptured huge left common iliac artery aneurysm of 13.5 cm
      in diameter, accompanied by colostomy due to colon ischemia which occurred during
      the operation. We discuss the pathophysiology and preventive strategy of colon
      ischemia during ruptured giant AAA repair. 

PMID- 26217622
TI  - Results of Open Surgical Repair of Chronic Juxtarenal Aortic Occlusion.
AB  - PURPOSE: The aim of study was to review the results of open surgical repair (OSR)
      of chronic juxtarenal aortic occlusion (JRAO). MATERIALS AND METHODS: We
      retrospectively reviewed the results of OSR performed in 47 patients (male, 92%;
      mean age, 59.9+/-9.3 years [range, 44-79]) with chronic JRAO during the past 21
      years. In order to reduce intraoperative renal ischemic time (RIT), we excised a
      portion of the occluded segment of the infrarenal aorta without proximal aortic
      clamping. We then performed suprarenal aortic clamping with both renal arteries
      clamped, removed the proximal aortic thrombus cap, confirmed both renal artery
      orifices, and moved the suprarenal aortic clamp to the infrarenal aorta to allow
      renal perfusion and standard aortoiliac reconstruction. We investigated early
      (<30 days) postoperative surgical morbidity (particularly renal function),
      operative mortality, and longterm patient survival. We conducted risk factor
      analysis for postoperative renal insufficiency. RESULTS: The mean intraoperative
      RIT was 10.7+/-5.5 minutes (range, 3-25), including 6 patients who underwent
      concomitant pararenal aortic thromboendarterectomy. Postoperatively, five (11%)
      patients had transient renal insufficiency, one had pneumonia, and one patient
      had an acute myocardial infarction. However, there was no operative mortality or
      newly developed dialysis-dependent renal failure. Postoperative follow up was
      available in 36 (77%) patients for a mean period of 6.3 years (range, 1 month-17
      years). Kaplan Meier calculations of patient survival at 5 and 10 years after
      surgery were 91.2% and 83.6%, respectively. CONCLUSION: We have experienced short
      RIT, acceptable early postoperative results and long-term survival after OSR of
      chronic JRAO.

PMID- 26217623
TI  - Endovascular Treatment of Isolated Bilateral Common Iliac Artery Aneurysms Using
      Iliac Branched Stent Graft.
AB  - Endovascular treatment of isolated bilateral common iliac artery aneurysm (CIAA)
      requires salvage of at least one internal iliac artery to prevent complications
      such as ischemic buttock claudication. We treated a case of bilateral CIAAs using
      an internal iliac branched stent graft. We report a case of a 58-year-old man who
      presented with bilateral CIAAs. The left internal iliac artery was occluded with
      coil embolization. The right internal iliac artery was saved by using a branched
      stent graft. The aneurysms were excluded with conventional endovascular aneurysm
      repair. Completion angiography showed technical success. Follow up computed
      tomography angiogram at three months showed complete exclusion of bilateral
      CIAAs, no endoleaks, and patent right internal iliac artery. There was no pelvic
      ischemic complication. We treated successfully a case of isolated bilateral CIAAs
      using an iliac branched stent graft. 

PMID- 26217624
TI  - Hypogastric Artery Transposition to Restore the Arterial Flow after Resection of
      the External Iliac Artery.
AB  - Tumors in the pelvic cavity frequently involve the iliac vessels. Common and
      external iliac arteries should be reconstructed to restore the flow to the lower
      extremity if the tumor directly invades these arteries. We report herein a 58
      year-old female patient with a 10*11 cm, recurred uterine leiomyosarcoma. We
      performed en bloc resection of the tumor mass including the sigmoid colon, left
      ureter and 5 cm of the left external iliac artery. After complete resection,
      restoration of arterial flow to the lower extremity was made with a novel
      strategy of hypogastric artery transposition. There was no evidence of tumor
      recurrence or vascular insufficiency at 12 months after surgery. 

PMID- 26217625
TI  - Surgical Management of an Infected Popliteal Artery Aneurysm.
AB  - Infective aneurysms are rare due to the antimicrobial advances and the early
      treatment of systemic infections. They represent a diagnostic and therapeutic
      challenge. The treatment for these cases is generally characterised by excision
      and reconstruction using an autologous vein graft. We describe a case of a 66
      year-old man who presented an 8 cm infected popliteal aneurysm where urgent
      surgical approach was performed. The vascular continuity was restored with a
      basilic vein. Clinical follow-up showed no signs of recurrent infection and
      patent bypass without any anastomotic pseudoaneurysm after a year. 

PMID- 26217626
TI  - Low-Grade Endometrial Stromal Sarcoma with Inferior Vena Cava Extension: First
      Report in Korea.
AB  - Low-grade endometrial stromal sarcoma (LGESS) with intravascular extension is
      very rare, with only 26 cases having been reported. We experienced a case of
      LGESS with inferior vena cava (IVC) extension. A 60-year-old female presented
      with left leg edema. She had a history of total hysterectomy, and was diagnosed
      of leiomyoma at that time. On imaging study, tumor masses were located around
      both common iliac veins (CIV), and within the CIV and IVC. The pelvic masses on
      both side and IVC mass were resected, and then the patient received adjuvant
      hormonal therapy and radiotherapy over the remnant pelvic masses. LGESS with IVC
      extension is difficult to distinguish from intravascular leiomyomatosis. LGESS is
      a malignant disease and commonly recurs, even in early stages. Accurate
      diagnosis, complete resection, proper adjuvant therapy and close follow-up are
      very important. 

PMID- 26217627
TI  - The Histological Changes of the Great Saphenous Vein at 2 Years after
      Cryosclerosis.
AB  - Cryosclerosis was developed at the end of the last decade. It is the endovenous
      cryoablation of the great saphenous vein and has been forgotten before the era of
      the endovenous ablation techniques began. The caused histomorphological changes
      of the vein weren't described before, especially, years after the procedure. A 31
      year-old female patient underwent cryosclerosis 2 years ago. Because of the
      recanalization of the great saphenous vein and recurrent varicosity, high
      ligation, cryostripping and phlebectomy of varices were performed. During
      surgery, a saphenous vein piece was harvested to investigate the
      histomorphological effect of cryosclerosis. Histological findings verified that
      recanalization had occurred, the vein wall had undergone remodeling, and the
      picro-sirius red stain showed collagen deposition in the whole vein wall.
      Cryosclerosis seems to result in the remodeling of the vein wall. 

PMID- 26217628
TI  - Consensus for the Treatment of Varicose Vein with Radiofrequency Ablation.
AB  - The objective of this paper is to introduce the schematic protocol of
      radiofrequency (RF) ablation for the treatment of varicose veins. INDICATION:
      anatomic or pathophysiologic indication includes venous diameter within 2-20 mm,
      reflux time >=0.5 seconds and distance from the skin >=5 mm or subfascial
      location. Access: it is recommended to access at or above the knee joint for
      great saphenous vein and above the mid-calf for small saphenous vein. Catheter
      placement: the catheter tip should be placed 2.0 cm inferior to the
      saphenofemoral or saphenopopliteal junction. Endovenous heat-induced thrombosis
      >=class III should be treated with low-molecular weight heparin. Tumescent
      solution: the composition of solution can be variable (e.g., 2% lidocaine 20
      mL+500 mL normal saline+bicarbonate 2.5 mL with/without epinephrine).
      Infiltration can be done from each direction. Ablation: two cycles' ablation for
      the first proximal segment of saphenous vein and the segment with the incompetent
      perforators is recommended. The other segments should be ablated one time. During
      RF energy delivery, it is recommended to apply external compression. Concomitant
      procedure: It is recommended to do simultaneously ambulatory phlebectomy. For
      sclerotherapy, it is recommended to defer at least 2 weeks. Post-procedural
      management: post-procedural ambulation is encouraged to reduce the thrombotic
      complications. Compression stocking should be applied for at least 7 days. Minor
      daily activity is not limited, but strenuous activities should be avoided for 2
      weeks. It is suggested to take showers after 24 hours and tub baths, swimming, or
      soaking in water after 2 weeks.

PMID- 26217629
TI  - Clinical Implications of Methylenetetrahydrofolate Reductase Mutations and Plasma
      Homocysteine Levels in Patients with Thromboembolic Occlusion.
AB  - PURPOSE: Hyperhomocysteinemia has been identified as an independent risk factor
      in arterial and venous thrombosis. Mutations in genes encoding
      methylenetetrahydrofolate reductase (MTHFR), involved in the metabolism of
      homocysteine, may account for reduced enzyme activity and elevated plasma
      homocysteine levels. In this study, we investigated the interrelation of MTHFR
      C677T genotype and level of homocysteine in patients with arterial and venous
      thrombosis. MATERIALS AND METHODS: We retrospectively reviewed the medical
      records of 146 patients who were diagnosed as having arterial and venous
      thrombosis. We excluded patients diagnosed with atrial fibrillation. We examined
      routinely the plasma concentration of total homocysteine level and MTHFR C677T
      polymorphism for evaluation of thrombotic tendency in all patients. Screening
      processes of MTHFR C677T polymorphism were performed by real-time polymerase
      chain reaction. RESULTS: Investigated groups consisted of thrombotic arterial
      occlusion in 48 patients and venous occlusion in 63 patients. The distribution of
      the three genotypes was as follows: homozygous normal (CC) genotype in 29
      (26.1%), heterozygous (CT) genotype in 57 (51.4%), and homozygous mutant (TT)
      genotype in 25 (22.5%) patients. There were no significant differences among
      individuals between each genotype group for baseline characteristics. Plasma
      concentration of homocysteine in patients with the TT genotype was significantly
      increased compared to the CC genotype (P<0.05). CONCLUSION: We observed a
      significant interaction between TT genotypes and homocysteine levels in our
      results. The results might reflect the complex interaction between candidate
      genes and external factors responsible for thrombosis.

PMID- 26217630
TI  - Transcatheter Arterial Embolization of Splenic Artery Aneurysms: A Single-Center
      Experience.
AB  - PURPOSE: The purpose of this study was to report on splenic artery aneurysms
      (SAAs) treated by transcatheter embolization in our single-center institution and
      to evaluate the clinical outcomes of patients with SAA by aneurysm location.
      MATERIALS AND METHODS: The original medical records and imaging results of 52
      patients with SAA treated in our center between January 1, 1995 and December 31,
      2013 were reviewed. Of these cases, 7 patients (13.5%) underwent surgery, 4
      patients (7.5%) underwent serial observation, and 1 patient had stent insertion
      only, leaving 40 patients (78.9%) who underwent endovascular treatment using a
      coil, with or without N-butyl-2-cyanoacrylate. RESULTS: Aneurysms were located in
      the distal third of the splenic artery in 27 patients (67.5%), in the middle
      third in 9 cases (22.5%), and in the proximal third in 4 cases (10%). Of the 40
      included patients, 25 were female (62.5%). Twenty-eight patients (70%) were
      asymptomatic. The mean aneurysm diameter was 2.48 cm (range, 0.8-6.0 cm).
      Complications involved pancreatitis (n=1) and early spleen infarction (n=29: <1/3
      in 14, 1/3-2/3 in 10, and >2/3 in 5). Postembolization syndrome was noted in 26
      patients (65%). There were no significant differences by aneurysm location in the
      postoperative increase in the values of white blood cells, amylase, lipase, and C
      reactive protein (P=0.067, P=0.881, P=0.891, and P=0.188, respectively).
      CONCLUSION: At our institution, endovascular management is safe, has high
      technical success, and represents the first-line treatment for SAA, regardless of
      aneurysm location.

PMID- 26217631
TI  - Prevalence and Risk Factors for the Peripheral Neuropathy in Patients with
      Peripheral Arterial Occlusive Disease.
AB  - PURPOSE: Peripheral neuropathy (PN) is known as a major contributor of the
      worsening of ischemic symptoms and the foot ulceration in patients with
      peripheral arterial occlusive disease (PAOD). However, there are few studies
      reporting the prevalence and risk factors for PN in PAOD. This study aimed to
      evaluate these issues for PN and to establish the importance of screening as
      additional treatment target for PN in PAOD. MATERIALS AND METHODS: A total of 52
      limbs with PAOD were enrolled from January 2011 to December 2012. PN was divided
      into radiculopathy, ischemic PN (IPN), and diabetic PN (DPN), based on
      electromyographic findings. We investigated the prevalence of overall PN and
      subtypes of PN and then analyzed the risk factors. RESULTS: The prevalence of
      overall PN in PAOD was 43 of 52 limbs (82.7%). In terms of subtypes of PN, the
      prevalence rate of radiculopathy and IPN was 30.8% and 23.1%, respectively. DPN
      showed in 22 limbs (73.3%) among 30 diabetic limbs. There was no significant
      correlation between each type of PN and ischemic symptoms. Our analysis showed
      that coronary artery disease (CAD) was a significant risk factor (P=0.01) for
      IPN, however, did not identify any significant risk factors for DPN. CONCLUSION:
      This present study indicated that most patients with PAOD had PN and CAD was a
      risk factor for IPN. In particular, PAOD with diabetes represented a higher
      prevalence for DPN. Our study suggests that PN should be evaluated and considered
      as another treatment target in patients with PAOD.

PMID- 26217632
TI  - Current Status of the Retrieval Rate of Retrievable Vena Cava Filters in a
      Tertiary Referral Center in Korea.
AB  - PURPOSE: The purpose of this study was to review the daily practice of inferior
      vena cava filters (IVCFs) in a tertiary referral center in Korea and to reveal
      the retrieval rate and the methods for improving it. MATERIALS AND METHODS:
      Through the electronic medical record system, a retrospective review was
      performed on 115 consecutive patients who underwent placement of retrievable
      IVCFs between February 2000 and January 2011 in Seoul National University
      Hospital. RESULTS: IVCF placement was done in 115 cases (113 patients). There
      were 68 men (59.1%), and the mean age was 58.5+/-15.5 years (range, 10-96 years).
      The affiliated departments were Vascular Surgery (57 cases, 49.6%), and Internal
      Medicine (20 cases, 17.4%). Advanced malignancy was the most commonly associated
      disease (n=30, 26%). The indications for IVCF placement were categorized;
      absolute indications in 36 cases (31.3%), relative indications in 78 cases
      (67.8%), and prophylactic use in 1 case (0.9%). The most common indications were
      thrombolysis/thrombectomy for iliocaval deep vein thrombosis (DVT) (n=55, 47.8).
      Of the 115 filters, 68 were retrieved (retrieval rate, 59%). The most common
      cause of non-retrieval was chronic high risk of venous thromboembolism in 24
      patients (51%), followed by residual proximal DVT (n=7, 15%), and negligence by
      unknown reasons (n=6, 13%). CONCLUSION: To improve the retrieval rate, the number
      of follow-up losses to vascular specialists must be decreased, which can be
      achieved by establishment of a dedicated IVC filter clinic, implementation of a
      filter registry, and regular education for medical teams and patients along with
      their families.

PMID- 26217633
TI  - Current Trends in the Management of Acute Deep Vein Thrombosis among Korean
      Vascular Surgeons.
AB  - PURPOSE: Venous thromboembolism (VTE) is a common life-threatening illness with
      significant morbidity and mortality rates. In recent years, the incidence of VTE
      has gradually increased in Korea. In this study, we evaluated the current trends
      in the management of acute deep vein thrombosis (DVT) in Korea. MATERIALS AND
      METHODS: A 20-item questionnaire was prepared and sent to 48 members of the
      Korean Society for Vascular Surgery. Each member worked in a different hospital.
      Twenty-two members participated in this study. RESULTS: The vascular surgery
      departments were primarily responsible for managing DVT. Ultrasound and computed
      tomography (CT) venography were chosen as the most common initial diagnostic
      tools. Eighty-two percent of participants routinely used the coagulation factor
      assay. Thrombolysis and inferior vena cava (IVC) filter insertion were performed
      mainly in the radiology departments. Seventy-seven percent of participants
      performed thrombolysis only if the thrombus age was less than 21 days. During
      thrombolysis, IVC filter was routinely inserted by 50% of respondents and removed
      within 14 days by 64% of respondents. Nearly all participants followed the 2012
      American College of Chest Physicians guidelines for anticoagulation therapy.
      CONCLUSION: The majority of Korean vascular surgeons followed the guidelines.
      However, CT was frequently used. Thrombolysis and IVC filter insertion were more
      frequently performed than recommended by the guidelines.

PMID- 26217634
TI  - Thrombolytic Therapy Using Urokinase for Management of Central Venous Catheter
      Thrombosis.
AB  - PURPOSE: The management of central venous catheters (CVCs) and catheter
      thrombosis vary among centers, and the efficacy of the methods of management of
      catheter thrombosis in CVCs is rarely reported. We investigated the efficacy of
      bedside thrombolysis with urokinase for the management of catheter thrombosis.
      MATERIALS AND METHODS: We retrospectively reviewed data from patients who had
      undergone CVC insertion by a single surgeon in a single center between April 2012
      and June 2014. We used a protocol for the management of CVCs and when catheter
      thrombosis was confirmed, 5,000 U urokinase was infused into the catheter.
      RESULTS: A total of 137 CVCs were inserted in 126 patients. The most common
      catheter-related complication was thrombosis (12, 8.8%) followed by infection (8,
      5.8%). Nine of the 12 patients (75%) with catheter thrombosis were recanalized
      successfully with urokinase. The rate of CVC recanalization was higher in the
      peripherally inserted central catheter (PICC) group (87.5%) than the chemoport
      group (50%). Reintervention for catheter-related thrombosis was needed in only
      2.2% of patients when thrombolytic therapy using urokinase was applied. Age <60
      years (P=0.035), PICC group (P=0.037) and location of the catheter tip above the
      superior vena cava (P=0.044) were confirmed as independent risk factors for
      catheter thrombosis. CONCLUSION: Thrombolysis therapy using urokinase could
      successfully manage CVC thrombosis. Reintervention was rarely needed when a
      protocol using urokinase was applied for the management of CVC thromboses.

PMID- 26217635
TI  - Hybrid Repair of Suprarenal Abdominal Aortic Aneurysm: Antegrade Debranching with
      Endovascular Aneurysm Repair.
AB  - We report a hybrid repair approach to the treatment of abdominal aortic aneurysm
      in patients with complex anatomies when typical endovascular aneurysm repair is
      limited due to juxtarenal involvement. A 63-year-old man presented with a 3-day
      history of fever and abdominal pain. He was diagnosed with acute cholecystitis
      along with incidental findings of two separate aneurysms of the abdominal aorta:
      a 3.7 cm saccular aneurysm at the suprarenal level, and a 6.6 cm fusiform
      aneurysm above the iliac bifurcation. He was treated with a hybrid technique
      involving an open approach for antegrade debranching of the superior mesenteric
      artery, and renal arteries and endovascular stent placement for treatment of an
      abdominal aortic aneurysm. The procedure was successfully completed with no
      adverse events as of the most recent 6-month outpatient follow-up. 

PMID- 26217636
TI  - Combination of Surgical Thrombectomy and Direct Thrombolysis in Acute Abdomen
      with Portal and Superior Mesenteric Vein Thrombosis.
AB  - Portal vein (PV) thrombosis (PVT) is a rare condition with development of
      thrombosis in the PV and its branches. Further extension to the splenic and
      superior mesenteric vein (SMV) causes intestinal infarction, with a reported
      mortality of up to 50%. A variety of treatments for PVT exist including
      anticoagulation, thrombolysis, surgical thrombectomy, insertion of shunts, bypass
      surgery, and liver transplantation. We experienced a case of successfully treated
      by surgical thrombectomy with direct thrombolysis into the thrombosed-PV and SMV.
      A 31-year-old male presented worsening abdominal pain for one week. Preoperative
      contrast enhanced computed tomography scan revealed complete PVT extending to
      splenic vein and SMV. The PV was accessed surgically and opened by thrombectomy;
      visual inspection confirmed proximal and distal flow. Urokinase was administered
      directly into the inferior mesenteric vein with successful decrease in thrombus
      burden. The complete angiography showed complete dissolution of thrombosis in PV
      and SMV. 

PMID- 26217637
TI  - Recent Advances in the Development of Experimental Animal Models Mimicking Human
      Aortic Aneurysms.
AB  - Aortic aneurysm is a common and life-threatening disease that can cause death
      from rupture. Current therapeutic options are limited to surgical or endovascular
      procedures because no pharmacological approaches have been proven to decrease the
      chance of expansion or rupture. The best approach to the management of aortic
      aneurysm would be the understanding and prevention of the processes involved in
      disease occurrence, progression, and rupture. There is a need for animal models
      that can reproduce the pathophysiological features of human aortic aneurysm, and
      several such models have been studied. This review will emphasize recent advances
      in animal models used in the determination of mechanisms and treatments of aortic
      aneurysms. 

PMID- 26217638
TI  - Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: A Failed
      Concept.
AB  - In 2009 Paolo Zamboni et al. implicated that chronic cerebral venous congestion
      lead to the development of multiple sclerosis. In this review, we examined the
      role of chronic cerbrospinal venous insufficiency in multiple sclerosis and the
      proposed therapy entailing venous angioplasty and stenting of extracranial veins
      with available evidence to date. 

PMID- 26217639
TI  - The Results of Self-Expandable Kissing Stents in Aortic Bifurcation.
AB  - PURPOSE: Kissing stent reconstruction is a widely used technique for the
      management of aortoiliac occlusive disease involving the aortic bifurcation or
      proximal common iliac arteries. The purpose of this study was to evaluate the
      results of self-expandable kissing stents in the aortic bifurcation. MATERIALS
      AND METHODS: We reviewed medical records of the patients treated with a kissing
      stent retrospectively from January 2007 to December 2012. The primary and
      secondary patencies were determined with Kaplan-Meier analysis, and Cox
      regression was used to determine the factors associated with patency. RESULTS: A
      total of 21 patients were included, and all were male (median age 53+/-15 years,
      range 48-78 years). Major symptoms were claudication (n=16, 61.9%), rest pain
      (n=5, 23.8%) and gangrene (n=5, 23.8%). Tans-Atlantic Inter-Society Consensus for
      the Management of Peripheral Arterial Disease (TASC) II classification was A 2
      (9.5%), B 5 (23.8%), C 7 (33.3%) and D 8 (38%). The mean follow-up was 40.7
      months. Major complication occurred in only one case which consisted of distal
      limb ischemia by emboli. Six patients developed symptomatic restenosis or
      occlusion. There was no major amputation, but minor amputation occurred in 3
      patients. There were 2 mortalities not associated with the procedure (lung cancer
      and intracranial hemorrhage). Primary patency was 89.6% at 1 year, 74.7% at 3
      years and 64.0% at 5 years. Secondary patency was 94.1% at 1 year, 88.2% at 3
      years and 68.6% at 5 years. No risk factors for restenosis or occlusion were
      identified. CONCLUSION: Self-expandable kissing stents can be used successfully
      with comparable patency for endovascular treatment of symptomatic atherosclerotic
      occlusive lesions in the aortic bifurcation area.

PMID- 26217640
TI  - On Postoperative Day Balloon Angioplasty for Salvage of Newly-Placed, Flow
      Limiting Native Arteriovenous Fistula.
AB  - PURPOSE: To report result and usefulness of immediate postoperative balloon
      angioplasty of de novo arteriovenous fistula (AVF) with limited flow just after
      creation. MATERIALS AND METHODS: From January 1, 2012 to March 31, 2014, 1,270
      patients received native AVF creations in a single vascular clinic. In twenty
      four patients (1.9% of total AVF creation), immediate postoperative balloon
      angioplasty was performed because of limited flow on palpation (only pulsation or
      no thrill) just after AVF creation. Medical records were reviewed
      retrospectively; technical success (restoration of AVF flow)/clinical success
      (growing as functional AVF) rate, maturation time, primary patency rate and
      fistula survival outcome were analyzed during a mean 10.8 months of follow-up.
      RESULTS: Technical/clinical success rate was 95.8% (23/24 cases); AVF flow was
      restored after balloon angioplasty, and all the flow-restorated AVFs grew as
      functional AVFs with mean+/-standard deviation, 4.5+/-1.5 weeks of maturation
      time. In seven (30.4%) patients, a secondary balloon angioplasty was needed to
      enhance maturation. The overall primary patency after immediate postoperative
      balloon angioplasty was 69.6% at 1 and 6 months and 59.0% at 12 months. There was
      1 complication (operation site hematoma). CONCLUSION: Immediate postoperative
      balloon angioplasty for salvage of newly-placed, flow-limiting native AVF is a
      useful, effective and safe procedure.

PMID- 26217641
TI  - Clinical Experience with a Hybrid Procedure Using the Adherent Clot Catheter for
      Salvage of Thrombosed Hemodialysis Access: A Comparison with the Standard Fogarty
      Balloon Catheter.
AB  - PURPOSE: This study aimed to compare the efficacy of two different catheters in
      hybrid surgery for salvage of thrombosed hemodialysis accesses. MATERIALS AND
      METHODS: The hybrid salvage procedure (surgical thrombectomy followed by
      endovascular angioplasty) of the thrombosed hemodialysis access, was performed
      using adherent clot (AC) catheter in 140 cases and Fogarty balloon catheter in 68
      cases. Procedure-related outcomes such as the clot removal status, clinical
      success, complications, and primary patency rates were analyzed retrospectively.
      RESULTS: The proportion of cases with good clot removal scores in the AC catheter
      and Fogarty balloon catheter groups was 77.9% and 91.2%, respectively (P=0.018).
      Clinical success was achieved in 90.7% of the cases in the AC catheter group and
      in 98.5% of the cases in the balloon catheter group (P=0.035). The mean patency
      rates of the two groups were 50.7% and 63.2% at 3 months, 40.7% and 47.1% at 6
      months, and 17.9% and 19.1% at 12 months. The complication rates (12.1% and 5.9%)
      and primary patency rates between the two catheters were not statistically
      different (P=0.328). On the analysis of the patency rate on access type of
      autologous (P=0.169) and prothetic graft (P=0.423), there was no significant
      difference between the two catheter groups. CONCLUSION: In terms of clot removal
      and clinical success, the AC catheter did not demonstrate better outcomes than
      the Fogarty balloon catheter. However, primary patency was not related to the
      type of catheter. Adherent clot catheter can be a useful alternative to Fogarty
      balloon catheter for thrombosed hemodialysis access.

PMID- 26217642
TI  - Different Effects of Orbital Shear Stress on Vascular Endothelial Cells:
      Comparison with the Results of In Vivo Study with Rats.
AB  - PURPOSE: An attempt was made to characterize the orbital shear stress by
      comparing the effects of orbital shear stress on vascular endothelial cells (ECs)
      with the results of animal experiments. MATERIALS AND METHODS: In the laboratory
      study, cultured ECs of well were distinguished by center and periphery then
      exposed to orbital shear stress using an orbital shaker. In the animal study,
      arteriovenous (AV) fistulas were made at the right femoral arteries of Sprague
      Dawley rats to increase the effect of the laminar flow. The condition of the
      stenosis was given on the left femoral arteries. The protein expression of
      inducible nitric oxide synthase (iNOS) and Akt phosphorylation were observed and
      compared. RESULTS: Under orbital shear stress, ECs showed an increase in iNOS
      protein expression and phosphorylation of Akt but most of the protein expressions
      derived from the periphery. When compared to the animal study, the increased
      expression of iNOS protein and phosphorylation of Akt were observed in the sample
      of AV fistula conditions and the iNOS protein expression was decreased in the
      stenosis conditions. CONCLUSION: Orbital shear stress did not show the
      characteristics of a pure turbulent shear force. By comparing the observation
      with the morphological changes of vascular ECs and site-specific protein
      expression on the results of animal experiments, uniform directional lamina shear
      stress forces were expressed at the periphery.

PMID- 26217643
TI  - Surgical Treatment of Infected Aortoiliac Aneurysm.
AB  - PURPOSE: Infected aneurysms of the abdominal aorta or iliac artery (IAAA) are
      rare but fatal and difficult to treat. The purpose of this study was to review
      the clinical presentations and outcomes of IAAA and to establish a treatment
      strategy for optimal treatment of IAAA. MATERIALS AND METHODS: Electronic medical
      records of 13 patients treated for IAAA at Seoul National University Hospital
      between March 2004 and December 2012 were retrospectively reviewed. RESULTS: Mean
      age was 64.2 (median 70, range 20-79) years. Aneurysms were located in the
      infrarenal aorta (n=7), iliac arteries (n=5), and suprarenal aorta (n=1). Seven
      patients underwent excision and in situ interposition graft, 3 underwent extra
      anatomical bypass, and 1 underwent endovascular repair. One patient with
      endovascular repair in an outside hospital refused resection, and only
      debridement was done, which revealed tuberculosis infection. One staphylococcal
      infection was caused by iliac stenting. Mycobacterium was the most common
      pathogen, followed by Klebsiella, Salmonella, and Staphylococcus. There were 3 in
      hospital mortalities and the causes were sepsis in 2 and aneurysm rupture in 1.
      The 3 extra-anatomic bypasses were all patent after 5-year follow-up. CONCLUSION:
      IAAA develops from various causes and various organisms. IAAA cases with gross
      pus were treated with extra-anatomic bypass, which was durable. In situ
      reconstruction is favorable for long term-safety and efficacy, but extensive
      debridement is essential.

PMID- 26217644
TI  - Long-Term Results of Catheter-Directed Thrombolysis Combined with Iliac Vein
      Stenting for Iliofemoral Deep Vein Thrombosis.
AB  - PURPOSE: We were going to access the effect of catheter-directed thrombolytic
      therapy (CDT) on post-thrombotic syndrome (PTS) and the long term effects of
      iliac vein stenting in acute iliofemoral deep vein thrombosis (IFDVT). MATERIALS
      AND METHODS: Fifty-six limbs in fifty-one patients (46 unilateral, 5 bilateral)
      were included from November 2001 through December 2007. Patients were classified
      based on the method of treatment: with stent implantation (n=37) and without
      stent implantation (n=19). The Villalta scale was chosen to assess for severity
      of PTS. The validated outcome measures were compared between the treatment
      groups. Statistical analysis was estimated according to the Kaplan-Meier test and
      Pearson chi-square test. RESULTS: Mean age was 57+/-13 years (range, 27-76
      years). Mean follow up duration was 56+/-12 months (range, 24-144 months).
      Overall 5-year primary patency rate was 66.1% (77.8% in the stenting group and
      42.1% in the non-stenting group) and showed statistically significant difference
      between the two groups (P=0.02). The recurrence rate of deep vein thrombosis was
      10/37 (27.1%) in the stenting group and 11/19 (57.9%) in the non-stenting group,
      respectively, which showed statistically significant difference between the two
      groups (P=0.024). Overall incidence of mild PTS was 8/30 (26.7%): 4/13 (30.8%) in
      the stenting group and 4/17 (23.5%) in the non-stenting group. None of the other
      factors showed statistically significant difference between the groups.
      CONCLUSION: Long term results of CDT in IFDVT were acceptable, and stent
      implantation to the iliac segment seems to have a good effect on the long term
      results. Therefore CDT with simultaneous stenting is recommended to improve long
      term results of IFDVT, if indicated.

PMID- 26217645
TI  - Open Surgical Repair of Abdominal Aortic Aneurysm Coexisting with Horseshoe
      Kidney.
AB  - Horseshoe kidney (HSK) is the most common congenital abnormality of the urologic
      system encountered during abdominal aortic aneurysm (AAA) surgery. Here, the
      authors report a case of AAA coexisting with HSK that was successfully treated by
      open surgery. Two accessory renal arteries of 2.5 mm and 3.1 mm were reimplanted.
      One of the implanted arteries later occluded and infarct of the isthmus
      developed, but there was no impairment of renal function. The authors discuss the
      complexity of the surgical treatment of AAA coexisting with HSK, and place focus
      on which accessory renal arteries should be reconstructed. 

PMID- 26217646
TI  - Successful Endovascular Stent-Graft Repair for Complicated Type B Aortic
      Dissection Developed in a Patient with Polycystic Kidney Disease.
AB  - Polycystic kidney disease (PCKD) is rarely associated with aortic dissection
      (AD), which is a life-threatening disease. Although endovascular stent-graft
      repair tends to show better outcomes than conventional therapies in complicated
      type B AD (TBAD), successful endovascular intervention of TBAD with malperfusion
      in a patient with PCKD has not been reported. This case shows a 37-year-old male
      who had sudden onset of sharply stabbing epigastric pain with severe
      hypertension, who was diagnosed with TBAD and PCKD by a computed tomography and
      initially underwent medical treatment. Four days after discharge, he was
      rehospitalized with left leg pain and paresthesia due to left lower leg
      malperfusion. Thoracic endovascular stent-graft repair covering the primary tear
      site of dissection was performed successfully, leading to a decrease in false
      lumen and improvement of symptoms. We report the case of complicated TBAD in a
      patient with PCKD treated with endovascular stent-graft repair. 

PMID- 26217647
TI  - Spontaneous Iliac Vein Rupture.
AB  - Spontaneous iliac vein rupture (SIVR) is a rare entity, which usually occurs
      without a precipitating factor, but can be a life-threatening emergency often
      requiring an emergency operation. This is a case report of SIVR in a 62-year-old
      female who presented to the emergency room with left leg swelling. Workup with
      contrast-enhanced computed tomography revealed a left leg deep vein thrombosis
      with May-Thurner syndrome and a hematoma in the pelvic cavity without definite
      evidence of arterial bleeding. She was managed conservatively without surgical
      intervention, and also underwent inferior vena cava filter insertion and
      subsequent anticoagulation therapy for pulmonary thromboembolism. This case shows
      that SIVR can be successfully managed with close monitoring and conservative
      management, and anticoagulation may be safely applied despite the patient
      presenting with venous bleeding. 

PMID- 26217648
TI  - Development of animal model for Bisphosphonates-related osteonecrosis of the jaw
      (BRONJ).
AB  - BACKGROUND: The aim of this study is to develop a rat model of bisphosphonates
      related osteonecrosis of the jaw (BRONJ) that would be verified with clinical,
      radiological and histological examination, and to confirm the influence of
      concurrent bisphosphonates and steroids use upon the occurrence and aggravation
      of BRONJ. METHODS: Twenty seven rats were divided into 3 groups; Saline group
      (I), Zoledronate group (II), Zoledronate and Dexamethasone group (III). Rats got
      weekly intraperitoneal injection for 4 times and extraction of left maxillary and
      mandibular 1st, 2nd molars were followed. Consecutive injections were performed,
      and blood sampling for measurements of C-terminal crosslinked telopeptide of type
      I collagen and tartrate-resistant acid phosphate 5b rats were performed at the
      time of 2, 4 and 8 weeks. And then, rats were sacrificed and evaluated
      clinically, radiologically and histologically. RESULTS: 12/18 (66.6 %) of
      experimental group were diagnosed as BRONJ. There was no significant difference
      in incidence between zoledronate alone group (ll) and concurrent use of
      zoledronate and dexamethasone group (lll). CONCLUSIONS: Concurrent use of
      bisphosphonates and steroids increase incidence of BRONJ compared to saline group
      (l). Zoledronate alone group (ll) and concurrent use of zoledronate and
      dexamethasone group (lll) shows same incidence of BRONJ. Based on this study, the
      rat treated with bisphosphonates and steroids can be considered a novel, reliable
      and reproducible model to understand pathology of BRONJ.

PMID- 26217649
TI  - Early Detection of Postpartum Depressive Symptoms in Mothers and Fathers and Its
      Relation to Midwives' Evaluation and Service Provision: A Community-Based Study.
AB  - BACKGROUND: Postpartum parental mental health problems pose a serious risk for
      child development and often remain undetected in postpartum primary care. Within
      the framework of the German Midwifes Prevention Study, the aim of this study was
      to investigate the presence of postpartum emotional distress in mothers and
      fathers, and the detection of distressed parents by midwives in a primary care
      setting. We also examined whether a temporal extension of the postpartum midwife
      care period is associated with greater use of midwife contacts and higher rates
      of referral to further professional support if needed. METHODS: Mothers, fathers,
      and midwives filled out questionnaires at 2 weeks (t 1) and 6 months (t 2)
      postpartum. Compared to standard care in the control group (CG), midwives in an
      intervention group (IG) offered extended postpartum care of 6 months postpartum.
      Parental psychological distress was assessed using the Edinburgh postnatal
      depression scale (EPDS). Midwives reported on parental psychological distress as
      well as the number of postpartum contacts and referrals to additional social- and
      health-care providers. RESULTS: Based on their ratings, midwives identified half
      of mothers and around one-quarter of fathers with elevated depressive symptoms
      according to the EPDS at t 1 and t 2. IG mothers used significantly more midwife
      contacts than CG mothers. IG mothers with high-postnatal psychological distress
      at t 2 used significantly more contacts than mothers with lower levels of
      distress. IG mothers with high-psychological distress at t 2 were referred to
      additional support services more often than mothers with lower levels of
      distress.

PMID- 26217650
TI  - Heart Rate Variability is Related to Disease Severity in Children and Young
      Adults with Pulmonary Hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PH) is frequently associated with an increase
      in sympathetic tone. This may adversely affect cardiac autonomic control.
      Knowledge about the clinical impact of autonomic dysfunction in patients with PH
      is limited. We aimed to assess whether parameters of heart rate variability (HRV)
      are related to disease severity in children with PH. METHODS: Parameters of HRV
      [SDNN, standard deviation of normal-to-normal intervals and SDANN, standard
      deviation of mean values for normal-to-normal intervals over 5 min] were
      determined from Holter electrocardiograms of 17 patients with PH without active
      intracardial shunt (10 female, mean age 12.8 +/- 8.7 years). Patients were
      allocated to two groups according to their disease severity: patients with
      moderate PH [ratio of pulmonary to systemic arterial pressure (PAP/SAP ratio) <
      0.75] (n = 11), patients with severe PH (PAP/SAP ratio > 0.75) (n = 6). An
      additional group of five adolescents with Eisenmenger syndrome (PAP/SAP ratio
      1.13 +/- 0.36) was included. RESULTS: Children with severe PH had significantly
      lower values of HRV [SDNN (73.8 +/- 21.1 vs. 164.9 +/- 38.1 ms), SDANN (62.2 +/-
      19.0 vs. 139.5 +/- 33.3 ms)] compared to patients with moderate PH (p = 0.0001
      for all). SDNN inversely correlated with ratio of PAP/SAP of PH patients without
      shunt (r = -0.82; p = 0.0002). Eisenmenger patients showed no significant
      difference of HRV [SDNN 157.6 +/- 43.2 ms, SDANN 141.2 +/- 45.3 ms] compared to
      patients with moderate PH without shunt (p > 0.05 for all). CONCLUSION: According
      to our results, children with severe PH may have alterations in HRV. Since HRV
      appears to be related to disease severity, it may therefore serve as an
      additional diagnostic marker of PH. Remarkably, although Eisenmenger patients
      have systemic pulmonary arterial pressures, they seem to have preserved HRV,
      which might reflect a more favorable autonomic adaptation.

PMID- 26217652
TI  - Working Harder at Working Together: Building Collaboration between Public Health
      and Health Care Delivery.

PMID- 26217653
TI  - Breakfast Clubs: Starting the Day in a Positive Way.
AB  - Breakfast clubs are widely promoted as having a beneficial impact on children's
      behavior at the start of the school day, which can be conducive to their learning
      within the classroom. However, the few available studies that have considered the
      impact of breakfast club attendance on children's behavior have yielded mixed
      results and no studies to date have directly observed children's behavior within
      the breakfast club setting. Using a combination of real-time observation and
      filmed breakfast club footage, the aims of the current study were to: (1) devise
      a set of observational criteria appropriate for use in the breakfast club
      setting; (2) investigate the occurrence of both positive and negative behaviors.
      A sample of 30 children aged between 3 and 11 years were recruited from 3,
      opportunistically sampled primary school breakfast clubs in the North East of
      England, UK. The behaviors they displayed within the breakfast club setting on
      two separate days were observed and coded for subsequent analysis. Results of the
      investigation showed that children's behavior could be classified into three
      positive and three negative behavioral categories. Using these categories to code
      children's behavior as they engaged in breakfast club showed that children
      displayed more positive than negative behaviors within the breakfast club setting
      and this was the case regardless of the type of activity (i.e., quiet or
      boisterous) children were involved in. Findings are discussed in relation to
      breakfast club policy, implementation, and evaluation. 

PMID- 26217651
TI  - Missing Cells: Pathophysiology, Diagnosis, and Management of (Pan)Cytopenia in
      Childhood.
AB  - Peripheral blood cytopenia in children can be due to a variety of acquired or
      inherited diseases. Genetic disorders affecting a single hematopoietic lineage
      are frequently characterized by typical bone marrow findings, such as lack of
      progenitors or maturation arrest in congenital neutropenia or a lack of
      megakaryocytes in congenital amegakaryocytic thrombocytopenia, whereas antibody
      mediated diseases such as autoimmune neutropenia are associated with a rather
      unremarkable bone marrow morphology. By contrast, pancytopenia is frequently
      associated with a hypocellular bone marrow, and the differential diagnosis
      includes acquired aplastic anemia, myelodysplastic syndrome, inherited bone
      marrow failure syndromes such as Fanconi anemia and dyskeratosis congenita, and a
      variety of immunological disorders including hemophagocytic lymphohistiocytosis.
      Thorough bone marrow analysis is of special importance for the diagnostic work-up
      of most patients. Cellularity, cellular composition, and dysplastic signs are the
      cornerstones of the differential diagnosis. Pancytopenia in the presence of a
      normo- or hypercellular marrow with dysplastic changes may indicate
      myelodysplastic syndrome. More challenging for the hematologist is the evaluation
      of the hypocellular bone marrow. Although aplastic anemia and hypocellular
      refractory cytopenia of childhood (RCC) can reliably be differentiated on a
      morphological level, the overlapping pathophysiology remains a significant
      challenge for the choice of the therapeutic strategy. Furthermore, inherited bone
      marrow failure syndromes are usually associated with the morphological picture of
      RCC, and the recognition of these entities is essential as they often present a
      multisystem disease requiring different diagnostic and therapeutic approaches.
      This paper gives an overview over the different disease entities presenting with
      (pan)cytopenia, their pathophysiology, characteristic bone marrow findings, and
      therapeutic approaches. 

PMID- 26217654
TI  - Full-Range Public Health Leadership, Part 2: Qualitative Analysis and Synthesis.
AB  - Public health leadership is an important topic in the era of U.S. health reform,
      population health innovation, and health system transformation. This study
      utilized the full-range leadership model in order to examine the public health
      leadership. We sought to understand local public health leadership from the
      perspective of local health department leaders and those who work with and for
      them. Public health leadership was explored through interviews and focus groups
      with directors (n = 4) and staff (n = 33) from local health departments.
      Qualitative analytic methods included reflexive journals, code-recode procedures,
      and member checking, with analysis facilitated by Atlas.ti v.6.0. Qualitative
      results supported and expanded upon previously reported quantitative findings.
      Leading by example and providing individual consideration to followers were found
      to be more important than other leader factors, such as intellectual stimulation,
      inspirational motivation, or idealized attributes of leaders. Having a clear and
      competent vision of public health, being able to work collaboratively with other
      community agencies, and addressing the current challenges to public health with
      creativity and innovation were also important findings. Idealized leadership
      behaviors and individual consideration should be the focus of student and
      professional development. Models that incorporate contextual considerations, such
      as the situational leadership model, could be utilized to ensure that optimal
      individual consideration is given to followers. 

PMID- 26217655
TI  - Out-of-Pocket Patient Payments for Public Health Care Services in Bulgaria.

PMID- 26217656
TI  - Capacity Building in Operational Research: More than One Way to Slice the Cake.

PMID- 26217657
TI  - Emotional Testimonies: An Ethnographic Study of Emotional Suffering Related to
      Migration from Mexico to Arizona.
AB  - It is increasingly argued that social and economic inequities poorly affect
      overall health. One of the means through which these inequities are translated to
      the body is via negative emotions, which carry known psychological and
      physiological responses. This paper examines migration-related psychosocial
      stressors impacting first-generation Mexican immigrants in southern Arizona, and
      reports on the primary emotional experiences immigrants associate with these
      stressors. Data were drawn from a qualitative, ethnographic study conducted over
      the course of 14 months during 2013-2014 with first-generation Mexican immigrants
      (N = 40) residing in Tucson Arizona and service providers working directly in the
      immigrant community (N = 32). Results indicate that the primary structural
      vulnerabilities that cause emotional hardship among immigrants are pre-migration
      stressors and adversity, dangerous border crossings, detention and deportation,
      undocumented citizenship status, family separation, and extreme poverty. Many of
      these factors have intensified over the past decade due to increased border
      security and state level anti-immigrant legislation in Arizona. Immigrants
      connected these hardships to the emotions of trauma (50%), fear (65%), depression
      (75%), loneliness (75%), sadness (80%), and stress (85%), and most respondents
      reported suffering from three or more of these emotions. Given the heavy
      emotional toll of migration and the direct impact that regional legislation and
      border security had on well-being, this paper argues that emotion be considered
      an important mechanism for health declines in the immigrant community. In order
      to stem the frequency and intensity of emotional stress in the Mexican immigrant
      community in Tucson, it is imperative to support organizations and policies that
      promote community building and support networks and also expand access to and
      availability of mental health services for immigrants regardless of documentation
      status. 

PMID- 26217658
TI  - Effectiveness of Personalized Feedback Alone or Combined with Peer Support to
      Improve Physical Activity in Sedentary Older Malays with Type 2 Diabetes: A
      Randomized Controlled Trial.
AB  - INTRODUCTION: Regular physical activity is an important aspect of self-management
      among older people with type 2 diabetes but many remain inactive. Interventions
      to improve physical activity levels have been studied but few studies have
      evaluated the effects of personalized feedback (PF) or peer support (PS); and
      there was no study on older people of Asian heritage. Hence, this trial evaluated
      whether PF only or combined with PS improves physical activity among older Malays
      with type 2 diabetes (T2DM) compared to usual care only. MATERIALS AND METHODS: A
      three-arm randomized controlled trial was conducted in a primary healthcare
      clinic in Malaysia. Sixty-nine sedentary Malays aged 60 years and older with T2DM
      who received usual diabetes care were randomized to PF or PS interventions or as
      controls for 12 weeks with follow-ups at weeks 24 and 36. Intervention groups
      performed unsupervised walking activity and received written feedback on physical
      activity. The PS group also received group and telephone contacts from trained
      peer mentors. The primary outcome was pedometer steps. Secondary outcomes were
      self-reported physical activity, cardiovascular risk factors, cardiorespiratory
      fitness, balance, quality of life, and psychosocial wellbeing. RESULTS: Fifty-two
      (75.4%) completed the 36-week study. The PS group showed greater daily pedometer
      readings than the PF and controls (p = 0.001). The PS group also had greater
      improvement in weekly duration (p < 0.001) and frequency (p < 0.001) of moderate
      intensity physical activity, scores on the Physical Activity Scale for Elderly (p
      = 0.003), 6-min walk test (p < 0.001), and social support from friends (p =
      0.032) than PF and control groups. CONCLUSION: The findings suggest that PF
      combined with PS in older Malays with T2DM improved their physical activity
      levels, cardiorespiratory fitness, and support from friends. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN71447000.

PMID- 26217659
TI  - Facile synthesis of cyclopentenone B1- and L1-type phytoprostanes.
AB  - Phytoprostanes (PhytoPs) represent non-enzymatic metabolites of alpha-linolenic
      acid (ALA), the essential omega-3 polyunsaturated fatty acid (PUFA) derived from
      plants. PhytoPs are present in the plant kingdom and represent endogenous
      mediators capable of protecting cells from oxidative stress damages in plants.
      Recently, it was found that such metabolites are present in cooking oil in high
      quantities, and also that B1-PhytoPs protect immature neurons from oxidant injury
      and promote differentiation of oligodendrocyte progenitors through PPAR-gamma
      activation. We report a novel and facile synthesis of natural 2,3-substituted
      cyclopentenone PhytoPs, 16-B1-PhytoP, and 9-L1-PhytoP. Our strategy is based on
      reductive alkylation at the 2-position of 1,3-cyclopentanedione using a recent
      protocol developed by Ramachary et al. and on a cross-coupling metathesis to
      access conjugate dienone system. In conclusion, this strategy permitted access to
      B1- and L1-PhytoPs in a relative short sequence process, and afford the
      possibility to easily develop analogs of PhytoPs. 

PMID- 26217660
TI  - Biochemical and Structural Properties of a Thermostable Mercuric Ion Reductase
      from Metallosphaera sedula.
AB  - Mercuric ion reductase (MerA), a mercury detoxification enzyme, has been tuned by
      evolution to have high specificity for mercuric ions (Hg(2+)) and to catalyze
      their reduction to a more volatile, less toxic elemental form. Here, we present a
      biochemical and structural characterization of MerA from the thermophilic
      crenarchaeon Metallosphaera sedula. MerA from M. sedula is a thermostable enzyme,
      and remains active after extended incubation at 97 degrees C. At 37 degrees C,
      the NADPH oxidation-linked Hg(2+) reduction specific activity was found to be 1.9
      MUmol/min?mg, increasing to 3.1 MUmol/min?mg at 70 degrees C. M. sedula MerA
      crystals were obtained and the structure was solved to 1.6 A, representing the
      first solved crystal structure of a thermophilic MerA. Comparison of both the
      crystal structure and amino acid sequence of MerA from M. sedula to mesophillic
      counterparts provides new insights into the structural determinants that underpin
      the thermal stability of the enzyme. 

PMID- 26217661
TI  - Cancer as a mitochondrial metabolic disease.
AB  - Cancer is widely considered a genetic disease involving nuclear mutations in
      oncogenes and tumor suppressor genes. This view persists despite the numerous
      inconsistencies associated with the somatic mutation theory. In contrast to the
      somatic mutation theory, emerging evidence suggests that cancer is a
      mitochondrial metabolic disease, according to the original theory of Otto
      Warburg. The findings are reviewed from nuclear cytoplasm transfer experiments
      that relate to the origin of cancer. The evidence from these experiments is
      difficult to reconcile with the somatic mutation theory, but is consistent with
      the notion that cancer is primarily a mitochondrial metabolic disease. 

PMID- 26217662
TI  - Hematological shift in goat kids naturally devoid of prion protein.
AB  - The physiological role of the cellular prion protein (PrP(C)) is incompletely
      understood. The expression of PrP(C) in hematopoietic stem cells and immune cells
      suggests a role in the development of these cells, and in PrP(C) knockout animals
      altered immune cell proliferation and phagocytic function have been observed.
      Recently, a spontaneous nonsense mutation at codon 32 in the PRNP gene in goats
      of the Norwegian Dairy breed was discovered, rendering homozygous animals devoid
      of PrP(C). Here we report hematological and immunological analyses of homozygous
      goat kids lacking PrP(C) (PRNP(Ter/Ter) ) compared to heterozygous (PRNP (+/Ter))
      and normal (PRNP (+/+)) kids. Levels of cell surface PrP(C) and PRNP mRNA in
      peripheral blood mononuclear cells (PBMCs) correlated well and were very low in
      PRNP (Ter/Ter), intermediate in PRNP (+/Ter) and high in PRNP (+/+) kids. The
      PRNP (Ter/Ter) animals had a shift in blood cell composition with an elevated
      number of red blood cells (RBCs) and a tendency toward a smaller mean RBC volume
      (P = 0.08) and an increased number of neutrophils (P = 0.068), all values within
      the reference ranges. Morphological investigations of blood smears and bone
      marrow imprints did not reveal irregularities. Studies of relative composition of
      PBMCs, phagocytic ability of monocytes and T-cell proliferation revealed no
      significant differences between the genotypes. Our data suggest that PrP(C) has a
      role in bone marrow physiology and warrant further studies of PrP(C) in erythroid
      and immune cell progenitors as well as differentiated effector cells also under
      stressful conditions. Altogether, this genetically unmanipulated PrP(C)-free
      animal model represents a unique opportunity to unveil the enigmatic physiology
      and function of PrP(C). 

PMID- 26217663
TI  - Editorial: Multi-omic data integration.

PMID- 26217664
TI  - A Rare Case of Congenital Diabetes Insipidus.
AB  - Congenital nephrogenic diabetes insipidus (NDI) is a conformation disease
      resulting from protein misfolding. Ninety percent of mutations result from the
      inactivating mutations of the arginine vasopressin receptor 2 (AVPR2) gene
      transmitted in an X-linked fashion, blocking the response to vasopressin,
      resulting in the inability to concentrate urine. Clinical features include
      polyuria, polydispsia, dehydration, and hypernatremia. They are generally more
      severely in affected males but present variably in females due to skewed
      inactivation of the X chromosome. We describe a case of a 40-year-old woman with
      a history of Type 2 diabetes mellitus, hyperlipidemia, and obesity, who presents
      with debilitating polyuria since the age of 5 with no clear diagnosis.
      Interestingly, her son was diagnosed with NDI. Genetic testing revealed that she
      was heterozygous for the Val88Met mutation in the AVPR2 gene while her son was
      hemizygous for the same. The patient has since been successfully treated with
      diuretics and a low solute diet. We highlight that although X-linked NDI patients
      are mostly males, it should be considered in symptomatic females to prevent
      delays in the diagnosis. Conformational diseases such as NDI are presently the
      subject of research using pharmacological chaperones to restore proper receptor
      membrane localization and function. 

PMID- 26217665
TI  - Progressive Resistance Exercise with Eccentric Loading for the Management of Knee
      Osteoarthritis.
AB  - INTRODUCTION: The patient was a 58-year-old African-American male with
      radiographic evidence of bilateral knee osteoarthritis (OA). He participated in a
      standardized 12-week eccentric strengthening program within a Veterans Affairs
      (VA) medical center. BACKGROUND: The use of an eccentric training paradigm may
      prove to be beneficial for older adults with knee OA since eccentric muscle
      actions are involved in the energy absorption at the knee joint during gait and
      controlled movement during stair descent. Furthermore, in comparison to standard
      muscle actions, eccentric muscle actions result in higher torque generation and a
      lower rate of oxygen consumption at a given level of perceived exertion.
      Therefore, this mode of progressive resistance exercise may be ideal for older
      adults. DISCUSSION: The patient completed an eccentric strengthening regimen for
      the knee flexors and extensors twice per week without an exacerbation of knee
      pain. Muscle morphology measures of the rectus femoris were measured using
      diagnostic ultrasound. Isokinetic measures of muscle peak torque were obtained at
      60 degrees /s and 180 degrees /s. Functional performance was assessed using a
      physical performance battery and stair-step performance was assessed from the
      linear displacement of the center of gravity trajectories obtained with a force
      plate. Visual analog scale pain ratings and self-reported global disease status
      were also documented. Post-exercise assessments revealed improvements in
      sonographic muscle size and tissue composition estimates, peak knee extensor
      torque (ranging from 60 to 253%), functional performance, and global disease
      status. CONCLUDING REMARKS: The patient exhibited improvements in muscle
      morphology, muscle strength, functional performance, pain, and global disease
      status after 12 weeks of an eccentric strengthening regimen. The intervention and
      outcomes featured in this case were feasible to implement within a VA medical
      center and merit further investigation.

PMID- 26217666
TI  - A Survey of Registered Dietitians' Concern and Actions Regarding Climate Change
      in the United States.
AB  - Dietary choices are a tool to reduce greenhouse gas emissions. While registered
      dietitians are on the front lines of food and nutrition recommendations, it is
      unclear how many are concerned with climate change and take action in practice in
      the United States. We explored concern about climate change among registered
      dietitians, and identified factors that may influence practice-related behaviors.
      Our study population included a random sample of all registered dietitians
      credentialed in the United States. Primary data were gathered using a cross
      sectional survey. Of the 570 survey responses, 75% strongly agreed or agreed that
      climate change is an important issue while 34% strongly agreed or agreed that
      dietitians should play a major role in climate change mitigation strategies.
      Thirty-eight percent engaged in activities that promoted diet as a climate change
      mitigation strategy. Vegetarian (p = 0.002) and vegan dietitians (p = 0.007) were
      significantly more likely than non-vegetarian and non-vegan dietitians to engage
      in activities that promoted diet as a climate change mitigation strategy.
      Overall, concern for climate change among dietitians varied significantly by the
      region of the country in which the dietitian resided, and awareness that animal
      products are implicated in climate change. Registered dietitians in the United
      States are concerned with climate change. However, there is a discrepancy between
      concern and practice-based actions. These results suggest the need for
      educational and experiential opportunities connecting climate change mitigation
      to dietetics practice. 

PMID- 26217667
TI  - Rats Prone to Obesity Under a High-Carbohydrate Diet have Increased Post-Meal CCK
      mRNA Expression and Characteristics of Rats Fed a High-Glycemic Index Diet.
AB  - We previously reported that rats prone to obesity exhibit an exaggerated increase
      in glucose oxidation and an exaggerated decline in lipid oxidation under a low
      fat high-carbohydrate (LF/HC) diet. The aim of the present study was to
      investigate the mechanisms involved in these metabolic dysregulations. After a 1
      week adaptation to laboratory conditions, 48 male Wistar rats were fed a LF/HC
      diet for 3 weeks. During weeks 2 and 3, glucose tolerance tests (GTT), insulin
      tolerance tests (ITT), and meal tolerance tests (MTT) were performed to evaluate
      blood glucose, plasma, and insulin. Glucose and lipid oxidation were also assayed
      during the GTT. At the end of the study, body composition was measured in all the
      rats, and they were classified as carbohydrate resistant (CR) or carbohydrate
      sensitive (CS) according to their adiposity. Before sacrifice, 24 of the 48 rats
      received a calibrated LF/HC meal. Liver, muscle, and intestine tissue samples
      were taken to measure mRNA expression of key genes involved in glucose, lipid,
      and protein metabolism. ITT, GTT, and MTT showed that CS rats were neither
      insulin resistant nor glucose intolerant, but mRNA expression of cholecystokinin
      (CCK) in the duodenum was higher and that of CPT1, PPARalpha, and PGC1alpha in
      liver were lower than in CR rats. From these results, we make the hypothesis that
      in CS rats, CCK increased pancreatic secretion, which may favor a quicker
      absorption of carbohydrates and consequently induces an enhanced inhibition of
      lipid oxidation in the liver, leading to a progressive accumulation of fat
      preferentially in visceral deposits. Such a mechanism may explain why CS rats
      share many characteristics observed in rats fed a high-glycemic index diet. 

PMID- 26217668
TI  - Labral Reconstruction: When to Perform and How.
AB  - Over the past decade, the understanding of the anatomy and function of the hip
      joint has continuously evolved, and surgical treatment options for the hip have
      significantly progressed. Originally, surgical treatment of the hip primarily
      involved resection of damaged tissue. Procedures that maintain and preserve
      proper hip anatomy, such as labral repair and femoroacetabular impingement
      correction, have shown superior results, in terms of pain reduction, increased
      function, and ability to return to activities. Labral reconstruction is a
      treatment option that uses a graft to reconstruct the native labrum. The
      technique and outcomes of labral reconstruction have been described relatively
      recently, and labral reconstruction is a cutting edge procedure that has shown
      promising early outcomes. The aim of this article is to review the current
      literature on hip labral reconstruction. We will review the indications for
      labral reconstruction, surgical technique and graft options, and surgical
      outcomes that have been described to date. Labral reconstruction provides an
      alternative treatment option for challenging intra-articular hip problems. Labral
      reconstruction restores the original anatomy of the hip and has the potential to
      preserve the longevity of the hip joint. This technique is an important tool in
      the orthopedic surgeon's arsenal for hip joint treatment and preservation. 

PMID- 26217669
TI  - Conformational heterogeneity of the Pfr chromophore in plant and cyanobacterial
      phytochromes.
AB  - Phytochromes are biological photoreceptors that can be reversibly photoconverted
      between a dark and photoactivated state. The underlying reaction sequences are
      initiated by the photoisomerization of the tetrapyrrole cofactor, which in plant
      and cyanobacterial phytochromes are a phytochromobilin (PPhiB) and a
      phycocyanobilin (PCB), respectively. The transition between the two states
      represents an on/off-switch of the output module activating or deactivating
      downstream physiological processes. In addition, the photoactivated state, i.e.,
      Pfr in canonical phytochromes, can be thermally reverted to the dark state (Pr).
      The present study aimed to improve our understanding of the specific reactivity
      of various PPhiB- and PCB-binding phytochromes in the Pfr state by analysing the
      cofactor structure by vibrational spectroscopic techniques. Resonance Raman (RR)
      spectroscopy revealed two Pfr conformers (Pfr-I and Pfr-II) forming a temperature
      dependent conformational equilibrium. The two sub-states-found in all
      phytochromes studied, albeit with different relative contributions-differ in
      structural details of the C-D and A-B methine bridges. In the Pfr-I sub-state the
      torsion between the rings C and D is larger by ca. 10 degrees  compared to Pfr
      II. This structural difference is presumably related to different hydrogen
      bonding interactions of ring D as revealed by time-resolved IR spectroscopic
      studies of the cyanobacterial phytochrome Cph1. The transitions between the two
      sub-states are evidently too fast (i.e., nanosecond time scale) to be resolved by
      NMR spectroscopy which could not detect a structural heterogeneity of the
      chromophore in Pfr. The implications of the present findings for the dark
      reversion of the Pfr state are discussed. 

PMID- 26217670
TI  - Time-resolved infrared spectroscopic techniques as applied to channelrhodopsin.
AB  - Among optogenetic tools, channelrhodopsins, the light gated ion channels of the
      plasma membrane from green algae, play the most important role. Properties like
      channel selectivity, timing parameters or color can be influenced by the exchange
      of selected amino acids. Although widely used, in the field of neurosciences for
      example, there is still little known about their photocycles and the mechanism of
      ion channel gating and conductance. One of the preferred methods for these
      studies is infrared spectroscopy since it allows observation of proteins and
      their function at a molecular level and in near-native environment. The
      absorption of a photon in channelrhodopsin leads to retinal isomerization within
      femtoseconds, the conductive states are reached in the microsecond time scale and
      the return into the fully dark-adapted state may take more than minutes. To be
      able to cover all these time regimes, a range of different spectroscopical
      approaches are necessary. This mini-review focuses on time-resolved applications
      of the infrared technique to study channelrhodopsins and other light triggered
      proteins. We will discuss the approaches with respect to their suitability to the
      investigation of channelrhodopsin and related proteins. 

PMID- 26217671
TI  - The use of ion mobility mass spectrometry to probe modulation of the structure of
      p53 and of MDM2 by small molecule inhibitors.
AB  - Developing drug-like molecules to inhibit the interactions formed by disordered
      proteins is desirable due to the high correlation of disorder with protein
      implicated in disease, but is challenging due in part to the lack of
      atomistically resolved and resolvable structures from conformationally dynamic
      systems. Ion mobility mass spectrometry (IM-MS) is well-positioned to assess
      protein ligand interactions along with the effect of a given inhibitor on
      conformation. Here we demonstrate the use of IM-MS to characterize the effect of
      two inhibitors RITA and Nutlin-3 on their respective binding partners: p53 and
      MDM2. RITA binds N-terminal transactivation domain of p53 (Np53) weakly,
      preventing direct observation of the complex in the gas phase. Nonetheless, upon
      incubation with RITA, we observe an alteration in the charge state distribution
      and in the conformational distributions adopted by Np53 in the gas phase. This
      finding supports the hypothesis that RITAs mode of action proceeds via a
      conformational change in p53. Circular dichroism corroborates our gas phase
      findings, showing a slight increase in secondary structure content on ligand
      incubation, and HDX-MS experiments also highlight the dynamic properties of this
      protein. Using the same approach we present data to show the effect of Nutlin-3
      binding to the N-terminal domain of MDM2 (N-MDM2), N-MDM2 presents as at least
      two conformational families in the absence of Nutlin-3. Upon Nutlin-3 binding,
      the protein undergoes a compaction event similar to that exhibited by RITA on
      Np53. This multi-technique approach highlights the inherent disorder in these
      systems; and in particular exemplifies the power of IM-MS as a technique to study
      transient interactions between small molecule inhibitors and intrinsically
      disordered proteins. 

PMID- 26217672
TI  - Globular and disordered-the non-identical twins in protein-protein interactions.
AB  - In biology proteins from different structural classes interact across and within
      classes in ways that are optimized to achieve balanced functional outputs. The
      interactions between intrinsically disordered proteins (IDPs) and other proteins
      rely on changes in flexibility and this is seen as a strong determinant for their
      function. This has fostered the notion that IDP's bind with low affinity but high
      specificity. Here we have analyzed available detailed thermodynamic data for
      protein-protein interactions to put to the test if the thermodynamic profiles of
      IDP interactions differ from those of other protein-protein interactions. We find
      that ordered proteins and the disordered ones act as non-identical twins
      operating by similar principles but where the disordered proteins complexes are
      on average less stable by 2.5 kcal mol(-1). 

PMID- 26217673
TI  - All-optical bidirectional neural interfacing using hybrid multiphoton holographic
      optogenetic stimulation.
AB  - Our understanding of neural information processing could potentially be advanced
      by combining flexible three-dimensional (3-D) neuroimaging and stimulation.
      Recent developments in optogenetics suggest that neurophotonic approaches are in
      principle highly suited for noncontact stimulation of network activity patterns.
      In particular, two-photon holographic optical neural stimulation (2P-HONS) has
      emerged as a leading approach for multisite 3-D excitation, and combining it with
      temporal focusing (TF) further enables axially confined yet spatially extended
      light patterns. Here, we study key steps toward bidirectional cell-targeted 3-D
      interfacing by introducing and testing a hybrid new 2P-TF-HONS stimulation path
      for accurate parallel optogenetic excitation into a recently developed hybrid
      multiphoton 3-D imaging system. The system is shown to allow targeted all-optical
      probing of in vitro cortical networks expressing channelrhodopsin-2 using a
      regeneratively amplified femtosecond laser source tuned to 905 nm. These
      developments further advance a prospective new tool for studying and achieving
      distributed control over 3-D neuronal circuits both in vitro and in vivo. 

PMID- 26217674
TI  - Optical coherence tomography for cross-sectional imaging of neural activity.
AB  - We report a functional optical coherence tomography cross-sectional scanner to
      detect neural activity using unmyelinated nerves dissected from squid. The
      nerves, unstained or stained with a voltage-sensitive dye, were imaged in a nerve
      chamber. Transient phase changes from backscattered light were detected during
      action potential propagation. The results show that the scanner can provide high
      spatiotemporal resolution cross-sectional images of neural activity ([Formula:
      see text]; [Formula: see text]; [Formula: see text] in [Formula: see text]). The
      advantage of this method compared to monitoring a single depth profile [Formula:
      see text] is a dramatic increase in the number of available sites that can be
      measured in two spatial dimensions [Formula: see text] with lateral scanning;
      therefore, the study demonstrates that two-dimensional monitoring of small-scale
      functional activity would also be feasible. 

PMID- 26217676
TI  - Data on force-dependent structural changes of chromatin fibers measured with
      magnetic tweezers.
AB  - The compaction of chromatin fibers regulates the accessibility of embedded DNA,
      highly associated with transcriptional activities [1]. Single molecule force
      spectroscopy has revealed the great details of the structural changes of
      chromatin fibers in the presence of external exerted force [2-7]. However, most
      of the studies focus on a specific force regime [2,3,8,9]. The data here show
      force-extension (FE) traces of chromatin fibers as measured with magnetic
      tweezers, covering the force regime from 0 pN to 27 pN. Those traces provide
      information for further studies at varied force regimes. 

PMID- 26217675
TI  - Evaluation of rigid registration methods for whole head imaging in diffuse
      optical tomography.
AB  - Functional brain imaging has become an important neuroimaging technique for the
      study of brain organization and development. Compared to other imaging
      techniques, diffuse optical tomography (DOT) is a portable and low-cost technique
      that can be applied to infants and hospitalized patients using an atlas-based
      light model. For DOT imaging, the accuracy of the forward model has a direct
      effect on the resulting recovered brain function within a field of view and so
      the accuracy of the spatially normalized atlas-based forward models must be
      evaluated. Herein, the accuracy of atlas-based DOT is evaluated on models that
      are spatially normalized via a number of different rigid registration methods on
      24 subjects. A multileveled approach is developed to evaluate the correlation of
      the geometrical and sensitivity accuracies across the full field of view as well
      as within specific functional subregions. Results demonstrate that different
      registration methods are optimal for recovery of different sets of functional
      brain regions. However, the "nearest point to point" registration method, based
      on the EEG 19 landmark system, is shown to be the most appropriate registration
      method for image quality throughout the field of view of the high-density cap
      that covers the whole of the optically accessible cortex. 

PMID- 26217677
TI  - Quantitative analysis of the Escherichia coli proteome.
AB  - Escherichia coli (strain ATCC 25922 in a stationary culture) cells were lysed
      with SDS and the lysates were processed according MED-FASP protocol. The released
      peptides were analyzed by LC-MS/MS. Protein content per bacterial cell was
      calculated on the basis of the DNA content. Absolute protein quantitation was
      performed using the 'Total Protein Approach'. The data are supplied in the
      article. 

PMID- 26217678
TI  - Data showing the compositional complexity of the mitochondrial proteome of a
      unicellular eukaryote (Acanthamoeba castellanii, supergroup Amoebozoa).
AB  - This article describes and directly links to 1033 Acanthamoeba castellanii
      mitochondrial protein sequences. Of these, 709 are supported by Mass Spectrometry
      (MS) data (676 nucleus-encoded and 33 mitochondrion-encoded). Two of these
      entries are previously unannotated mtDNA-encoded proteins, which we identify as
      highly divergent mitochondrial ribosomal proteins. Our analysis corrects many A.
      castellanii protein sequences that were incorrectly inferred previously from
      genomic data deposited in NCBI. 

PMID- 26217679
TI  - Data for a comparative proteomic analysis of chloroplast biogenesis (clb)
      mutants.
AB  - This data article contains data related to the research article titled Proteomic
      analysis of chloroplast biogenesis (clb) mutants uncovers novel proteins
      potentially involved in the development of Arabidopsis thaliana chloroplasts (de
      Luna-Valdez et al., 2014) [1]. This research article describes the 2-D PAGE-based
      proteomic analysis of wild-type and four mutant lines (cla1-1, clb2, clb5 and
      clb19) affected in the development of Arabidopsis thaliana chloroplasts. The
      report concludes with the discovery of three proteins potentially involved in
      chloroplast biogenesis. The information presented here represent the tables and
      figures that detail the processing of the raw data obtained from the image
      analysis of the 2-D PAGE gels. 

PMID- 26217681
TI  - From hundreds to thousands: Widening the normal human Urinome.
AB  - The limits on protein detection in urine are unknown. Improving the analytical
      approach to detection would increase the number of identified proteins and
      potentially strengthen their predictive potential in diseases. Here, we present
      the data that resulted from a combination of analytical procedures for maximizing
      sensitivity and reproducibility of normal human urinary proteome analysis. These
      procedures are ultracentrifugation, vesicle separation, combinatorial peptide
      ligand libraries (CPLL) and solvent removal of pigments. Proteins were identified
      by an Orbitrap Velos Mass Spectrometry. 3429 proteins are characterized, 1724 of
      which are novel discoveries. The data are related to Santucci et al. (in press)
      [1] and available both here and at ChorusProject.org under project name "From
      hundreds to thousands: widening the normal human Urinome". The material supplied
      to Chorus Progect.org includes technical MS spectra data only. 

PMID- 26217680
TI  - Data from a proteomic analysis of colonic fibroblasts secretomes.
AB  - The tumor cell proliferation, migration and invasion were influenced by the
      interaction between the cancer cells and their microenvironment. In current
      study, we established two pairs of the primary fibroblast cultures from
      colorectal adenocarcinoma tissues and the normal counterparts and identified 227
      proteins in the colonic fibroblast secretomes; half of these proteins were novel.
      The mass spectrometry data and analyzed results presented here provide novel
      insights into the molecular characteristics and modulatory role of colon cancer
      associated fibroblasts. The data is related to "Identification of colonic
      fibroblast secretomes reveals secretory factors regulating colon cancer cell
      proliferation" by Chen et al. [1]. 

PMID- 26217682
TI  - Data set for the proteomics analysis of the endomembrane system from the
      unicellular Entamoeba histolytica.
AB  - Entamoeba histolytica is the protozoan parasite agent of amebiasis, an infectious
      disease of the human intestine and liver. This parasite contact and kills human
      cells by an active process involving pathogenic factors. Cellular traffic and
      secretion activities are poorly characterized in E. histolytica. In this work, we
      took advantage of a wide proteomic analysis to search for principal components of
      the endomembrane system in E. histolytica. A total of 5683 peptides matching with
      1531 proteins (FDR of 1%) were identified which corresponds to roughly 20% of the
      total amebic proteome. Bioinformatics investigations searching for domain
      homologies (Smart and InterProScan programs) and functional descriptions (KEGG
      and GO terms) allowed this data to be organized into distinct categories. This
      data represents the first in-depth proteomics analysis of subcellular
      compartments in E. histolytica and allows a detailed map of vesicle traffic
      components in an ancient single-cell organism that lacks a stereotypical ER and
      Golgi apparatus to be established. The data are related to [1]. 

PMID- 26217684
TI  - Data for mitochondrial proteomic alterations in the developing rat brain.
AB  - Mitochondria are a critical organelle involved in many cellular processes, and
      due to the nature of the brain, neuronal cells are almost completely reliant on
      these organelles for energy generation. Due to the fact that biomedical research
      tends to investigate disease state pathogenesis, one area of mitochondrial
      research commonly overlooked is homeostatic responses to energy demands.
      Therefore, to elucidate mitochondrial alterations occurring during the
      developmentally important phase of E18 to P7 in the brain, we quantified the
      proteins in the mitochondrial proteome as well as proteins interacting with the
      mitochondria. We identified a large number of significantly altered proteins
      involved in a variety of pathways including glycolysis, mitochondrial
      trafficking, mitophagy, and the unfolded protein response. These results are
      important because we identified alterations thought to be homeostatic in nature
      occurring within mitochondria, and these results may be used to identify any
      abnormal deviations in the mitochondrial proteome occurring during this period of
      brain development. A more comprehensive analysis of this data may be obtained
      from the article "Proteomic analysis of mitochondria from embryonic and postnatal
      rat brains reveals response to developmental changes in energy demands" in the
      Journal of Proteomics. 

PMID- 26217683
TI  - Data for chicken semen proteome and label free quantitative analyses displaying
      sperm quality biomarkers.
AB  - Understanding of biology of the avian male gamete is essential to improve the
      conservation of genetic resources and performances in farming. In this study, the
      semen proteome of the main domestic avian species (Gallus gallus) and evaluation
      of the molecular phenotype related to sperm quality were investigated using GeLC
      MS/MS approach and label-free quantitative proteomic based on Spectral Counting
      (SC) and extracted ion chromatograms (XIC) methods. Here we describe in details
      the peptide/protein inventory of chicken ejaculated spermatozoa (SPZ) and seminal
      plasma (SP). We also show differential analyses of chicken semen (SPZ and
      corresponding SP) from 11 males demonstrating different levels of fertilizing
      capacity and sperm motility. The interpretation and description of these data can
      be found in a research article published by Labas and colleagues in the Journal
      of Proteomics in 2014 [1]. This is a new resource for exploring the molecular
      mechanisms involved in fertilizing capacity and to reveal new sets of fertility
      biomarkers. 

PMID- 26217685
TI  - Data from an integrative approach decipher the surface proteome of
      Propionibacterium freudenreichii.
AB  - The surface proteins of the probiotic Propionibacterium freudenreichii were
      inventoried by an integrative approach that combines in silico protein
      localization prediction, surface protein extraction, shaving and fluorescent
      CyDye labeling. Proteins that were extracted and/or shaved and/or labeled were
      identified by nano-LC-MS/MS following trypsinolysis. This method's combination
      allowed to confirm detection of true surface proteins involved in host/probiotic
      interactions. The data, supplied in this article, are related to the research
      article entitled "Surface proteins of P. freudenreichii are involved in its anti
      inflammatory properties" (Le Marechal et al., 2014 [6]). 

PMID- 26217686
TI  - Data in support of comparative proteomics analysis of superior and inferior
      spikelets in hybrid rice during grain filling and response of inferior spikelets
      to drought stress using isobaric tags for relative and absolute quantification.
AB  - We provide the raw data for protein and peptide identification and quantization
      of superior and inferior spikelets in hybrid rice during grain filling. The mass
      spectrometry proteomics data have been deposited to the Proteome Xchange
      Consortium via the PRIDE partner repository with the dataset identifier
      PXD001046. Our data presented here is also related to the article "Comparative
      proteomics analysis of superior and inferior spikelets in hybrid rice during
      grain filling and response of inferior spikelets to drought stress using isobaric
      tags for relative and absolute quantification "in the Journal of Proteomics [1]. 

PMID- 26217687
TI  - Data for a proteomic analysis of p53-independent induction of apoptosis by
      bortezomib.
AB  - This data article contains data related to the research article entitled, "A
      proteomic analysis of p53-independent induction of apoptosis by bortezomib in 4T1
      breast cancer cell line" by Yerlikaya et al. [1]. The research article presented
      2-DE and nLC-MS/MS based proteomic analysis of proteasome inhibitor bortezomib
      induced changes in the expression of cellular proteins. The report showed that
      GRP78 and TCEB2 were over-expressed in response to treatment with bortezomib for
      24 h. In addition, the report demonstrated that Hsp70, the 26S proteasome non
      ATPase regulatory subunit 14 and sequestosome 1 were increased at least 2 fold in
      p53-deficient 4T1 cells. The data here show for the first time the increased
      expressions of Card10, Dffb, Traf3 and Trp53bp2 in response to inhibition of the
      26S proteasome. The information presented here also shows that both Traf1 and
      Xiap (a member of IAPs) are also downregulated simultaneously upon proteasomal
      inhibition. The increases in the level of Card10 and Trp53bp2 proteins were
      verified by Western blot analysis in response to varying concentrations of
      bortezomib for 24 h. 

PMID- 26217688
TI  - Sequence conservation of linker histones between chicken and mammalian species.
AB  - The percent identity matrices of two sequence multiple alignments between linker
      histones from chicken and mammalian species are described. Linker histone protein
      sequences for chicken, mouse, rat and humans, available on public databases were
      used. This information is related to the research article entitled
      "Identification of novel post-translational modifications in linker histones from
      chicken erythrocytes"published in the Journal of Proteomics [1]. 

PMID- 26217689
TI  - Data set for the proteomic inventory and quantitative analysis of chicken uterine
      fluid during eggshell biomineralization.
AB  - Chicken eggshell is the protective barrier of the egg. It is a biomineral
      composed of 95% calcium carbonate on calcitic form and 3.5% organic matrix
      proteins. Mineralization process occurs in uterus into the uterine fluid. This
      acellular fluid contains ions and organic matrix proteins precursors which are
      interacting with the mineral phase and control crystal growth, eggshell structure
      and mechanical properties. We performed a proteomic approach and identified 308
      uterine fluid proteins. Gene Ontology terms enrichments were determined to
      investigate their potential functions. Mass spectrometry analyses were also
      combined to label free quantitative analysis to determine the relative abundance
      of 96 proteins at initiation, rapid growth phase and termination of shell
      calcification. Sixty four showed differential abundance according to the
      mineralization stage. Their potential functions have been annotated. The complete
      proteomic, bioinformatic and functional analyses are reported in Marie et al., J.
      Proteomics (2015) [1]. 

PMID- 26217690
TI  - Data set for the genome-wide transcriptome analysis of human epidermal
      melanocytes.
AB  - The data in this article contains data related to the research articled entitle
      Genome-wide transcriptome analysis of human epidermal melanocytes. This data
      article contains a complete list of gene and transcript isoform expression in
      human epidermal melanocytes. Transcript isoforms that are differentially
      expressed in lightly versus darkly pigmented melanocytes are identified. We also
      provide data showing the gene expression profiles of cell signaling gene families
      (receptors, ion channels, and transcription factors) in melanocytes. The raw
      sequencing data used to perform this transcriptome analysis is located in the
      NCBI Sequence Read Archive under Accession No. SRP039354
      http://dx.doi.org/10.7301/Z0MW2F2N. 

PMID- 26217691
TI  - Data supporting the identification of anti-metastatic drug and natural compound
      targets in isogenic colorectal cancer cells.
AB  - To investigate molecular therapeutic targets in cancer metastasis, comparative
      proteomic analysis was performed using the isogenic colorectal cancer cell lines
      SW480 and SW620. Two potential metastasis related molecular targets were
      identified: fatty acid synthase and histone H4. Subsequently, metastatic SW620
      cells were treated with six anti-cancerous components and suppressive effects
      were observed in target protein expression. Through comprehensive proteomic
      analysis, three of the tested compounds, oxaliplatin, ginsenoside 20(S)-Rg3 and
      curcumin, were determined to have a suppressive effect on fatty acid synthase and
      histone H4 expression [1]. The current article contains one table exhibiting a
      list of proteins differentially expressed in metastatic SW620 cell lines compared
      to the primary SW480 cell line (Supplementary Table 1). Additionally, six tables
      demonstrate proteome changes in SW620 resulting from the treatment of three
      chemotherapeutics and three natural components (Supplementary Tables 1-7). The
      anti-metastatic components revealed by the current proteomic analysis represent
      promising chemotherapeutic candidates for the treatment of colorectal
      adenocarcinoma. 

PMID- 26217692
TI  - BioID data of c-MYC interacting protein partners in cultured cells and xenograft
      tumors.
AB  - BioID was performed using FlagBirA* (the R118G biotin ligase mutant protein) and
      FlagBirA*-Myc in HEK293 T-REx cells maintained both under standard cell culture
      conditions and as mouse xenografts. The mass spectrometry dataset acquired in
      this study has been uploaded to the MassIVE repository with ID: MSV000078518, and
      consists of 28 *.raw MS files acquired on an Orbitrap Velos instrument, collected
      in data-dependent mode. iProphet processed MS/MS search results are also included
      as a reference. This study has been published as "BioID identifies novel c-MYC
      interacting partners in cultured cells and xenograft tumors", by Dingar et al. in
      the Journal of Proteomics, 2014 [1]. 

PMID- 26217693
TI  - Data in support of peptidomic analysis of spermatozoa during epididymal
      maturation.
AB  - The final differentiation of the male germ cell occurs in the epididymal duct
      where the spermatozoa develop the ability to be motile and fertilize an ovum.
      Understanding of these biological processes is the key to understanding and
      controlling male fertility. Comparative studies between several epididymal
      maturation states could be an informative approach to finding sperm modifications
      related to maturation and fertility. Here we show the data from differential
      peptidomic/proteomic analyses on spermatozoa isolated from 4 epididymal regions
      (immature to mature stage) using a profiling approach based on MALDI-TOF mass
      spectrometry and, combined to top-down MS in order to identify peptidoforms and
      proteoforms. By this way, 172m/z peaks ranging between 2 and 20 kDa were found to
      be modified during maturation of sperm. A total of 62m/z were identified
      corresponding to 32 different molecular species. The interpretation of these data
      can be found in the research article published by Labas and colleagues in the
      Journal of Proteomics in 2014 [1]. 

PMID- 26217694
TI  - "Publish or perish": Should this still be true for your data?

PMID- 26217695
TI  - Data in support of metabolic reprogramming in transformed mouse cortical
      astrocytes: A proteomic study.
AB  - 2D-DIGE analysis coupled with mass spectrometry is a global, without a priori,
      comparative proteomic approach particularly suited to identify and quantify
      enzymes isoforms and structural proteins, thus making it an efficient tool for
      the characterization of the changes in cell phenotypes that occur in
      physiological and pathological conditions. In this data article in support of the
      research article entitled "Metabolic reprogramming in transformed mouse cortical
      astrocytes: a proteomic study" [1] we illustrate the changes in protein profile
      that occur during the metabolic reprogramming undergone by cultured mouse
      astrocytes in a model of in-vitro cancerous transformation [2]. 

PMID- 26217696
TI  - Data for iTRAQ-based quantitative proteomics analysis of Brassica napus leaves in
      response to chlorophyll deficiency.
AB  - The essential pigment chlorophyll (Chl) plays important roles in light harvesting
      and energy transfer during photosynthesis. Here we present the data from a
      comparative proteomic analysis of chlorophyll-deficient Brassica napus mutant
      cde1 and its corresponding wild-type using the iTRAQ approach (Pu Chu et al.,
      2014 [1]). The distribution of length and number of peptides, mass and sequence
      coverage of proteins identified was calculated, and the repeatability of the
      replicates was analyzed. A total of 443 differentially expressed proteins were
      identified in B. napus leaves, including 228 down-accumulated proteins mainly
      involved in photosynthesis, porphyrin and chlorophyll metabolism, biosynthesis of
      secondary metabolites, carbon fixation and 215 up-accumulated proteins that
      enriched in the spliceosome, mRNA surveillance and RNA degradation. 

PMID- 26217697
TI  - The quantitative changes in the yeast Hsp70 and Hsp90 interactomes upon DNA
      damage.
AB  - The molecular chaperones Hsp70 and Hsp90 participate in many important cellular
      processes, including how cells respond to DNA damage. Here we show the results of
      applied quantitative affinity-purification mass spectrometry (AP-MS) proteomics
      to understand the protein network through which Hsp70 and Hsp90 exert their
      effects on the DNA damage response (DDR). We characterized the interactomes of
      the yeast Hsp70 isoform Ssa1 and Hsp90 isoform Hsp82 before and after exposure to
      methyl methanesulfonate. We identified 256 chaperone interactors, 146 of which
      are novel. Although the majority of chaperone interaction remained constant under
      DNA damage, 5 proteins (Coq5, Ast1, Cys3, Ydr210c and Rnr4) increased in
      interaction with Ssa1 and/or Hsp82. This data presented here are related to [1]
      (Truman et al., in press). The mass spectrometry proteomics data have been
      deposited to the ProteomeXchange Consortium
      (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository
      (Vizcaino et al. (2013) [2]) with the dataset identifier PXD001284. 

PMID- 26217698
TI  - Data set from the proteomic analysis of Bithynia siamensis goniomphalos snails
      upon infection with the carcinogenic liver fluke Opisthorchis viverrini.
AB  - The snail Bithynia siamensis goniomphalos acts as the first intermediate host for
      the human liver fluke Opisthorchis viverrini, the major cause of
      cholangiocarcinoma (CCA) in Northeast Thailand. This data article contains the
      results obtained from the analysis of the proteins differentially expressed in
      the snail B. siamensis goniomphalos upon infection with O. viverrini. It contains
      the data generated from iQuantitator software including a pdf of each sample with
      a protein's relative expression summary and a per-protein detailed analysis of
      all time points studied and an excel file for each sample containing the raw data
      from iQuantitator analysis, including ID, mean, standard deviation, credible
      interval, log2 and description for every protein identified in each of the
      samples. 

PMID- 26217699
TI  - Mass spectrometry and bioinformatics analysis data.
AB  - 2DE and 2D-DIGE based proteomics analysis of serum from women with endometriosis
      revealed several proteins to be dysregulated. A complete list of these proteins
      along with their mass spectrometry data and subsequent bioinformatics analysis
      are presented here. The data is related to "Investigation of serum proteome
      alterations in human endometriosis" by Dutta et al. [1]. 

PMID- 26217700
TI  - Data in support of comparative physiology and proteomic analysis of two wheat
      genotypes contrasting in drought tolerance.
AB  - Here, we present the data from a comparative physiology and proteomics approach
      used to analyze the response of two wheat genotypes (SERI M 82 (SE) and
      SW89.5193/kAu2 (SW)) with contrasting responses to drought stress. Proteomic
      analysis resulted in identification of 49 unique proteins with significant change
      in abundance (2-fold) under water shortage in roots and leaves. Gene ontology
      analysis of drought-responsive proteins (DRPs) suggested an induction of proteins
      related to cell wall biogenesis, ATP synthesis, photosynthesis, and
      carbohydrate/energy metabolism in leaves under stress condition. A large fraction
      of root proteins were identified to be involved in defense and oxidative stress
      response. In addition, a significant change was detected in proteins related to
      protein synthesis, ATP synthesis, and germin-like proteins in response to drought
      stress. A detailed analysis of this data may be obtained from Ref. [1]. 

PMID- 26217701
TI  - Raw data for the identification of SUMOylated proteins in S. cerevisiae subjected
      to two types of osmotic shock, using affinity purification coupled with mass
      spectrometry.
AB  - The small ubiquitin-related modifier (SUMO) "stress response" (SSR) is a poorly
      understood evolutionarily conserved phenomenon in which steady-state SUMO
      conjugate levels are dramatically increased in response to environmental
      stresses. Here we describe the data acquired using affinity-purification coupled
      with mass spectrometry to identify proteins that are SUMOylated in response to
      two different types of osmotic stress, 1 M sorbitol and 1 M KCl. The mass
      spectrometry dataset described here has been uploaded to the MassIVE repository
      with ID: MSV000078739, and consists of 32 raw MS files acquired in data-dependent
      mode on a Thermo Q-Exactive instrument. iProphet-processed MS/MS search results
      and associated SAINT scores are also included as a reference. These data are
      discussed and interpreted in "The S. cerevisiae SUMO stress response is a
      conjugation-deconjugation cycle that targets the transcription machinery", by
      Lewicki et al. in the Journal of Proteomics, 2014 [1]. 

PMID- 26217702
TI  - Two-dimensional gel electrophoresis data for proteomic profiling of Sporothrix
      yeast cells.
AB  - Sporotrichosis is a chronic infection of the skin and subcutaneous tissues of
      human and other mammals caused by a complex of cryptic dimorphic fungi in the
      plant-associated order Ophiostomatales. With major differences between routes of
      transmission, Sporothrix infections are emerging as new threat in tropical and
      subtropical areas, particularly in form of outbreaks. The mechanisms underlying
      the pathogenesis and invasion of Sporothrix spp. are still poorly understood and
      many virulence factors remain unidentified. In this scenario, a global analysis
      of proteins expressed by clinical Sporothrix species combined with the
      identification of seroreactive proteins is overdue. Optimization of sample
      preparation and electrophoresis conditions are key steps toward reproducibility
      of gel-based proteomics assays. We provide the data generated using an efficient
      protocol of protein extraction for rapid and large-scale proteome analysis using
      two-dimensional gel electrophoresis. The protocol was established and optimized
      for pathogenic and non-pathogenic Sporothrix spp. including Sporothrix
      brasiliensis (CBS 132990), Sporothrix schenckii sensu stricto (CBS 132974),
      Sporothrix globosa (CBS 132922), and Sporothrix mexicana (CBS 120341). The data,
      supplied in this article, are related to the research article entitled
      "Immunoproteomic analysis reveals a convergent humoral response signature in the
      Sporothrix schenckii complex" (Rodrigues et al., 2014 [1]). 

PMID- 26217703
TI  - Genome-wide transcriptional profiling data from chronic cutaneous lupus
      erythematosus (CCLE) peripheral blood.
AB  - The disease Lupus erythematosus (LE), exhibits a variety of clinical
      manifestations with potentially wide-ranging multi-organ damage to joints,
      tendons, kidney, lung, heart, blood vessels, central nervous system and skin
      [1,2] Systemic changes are likely to trigger organ specific manifestation of the
      disease. Here, we provide the data examined to address the gap in knowledge
      regarding causes and mechanisms contributing to the autoimmune attack on skin in
      chronic cutaneous lupus erythematosus (CCLE). The raw gene expression data files
      (CEL files) are provided with this article [3]. 

PMID- 26217704
TI  - Data set for the mass spectrometry based exoproteome analysis of Aspergillus
      flavus isolates.
AB  - Aspergillus flavus is one of the predominant causative organisms of mycotic
      keratitis in tropical parts of the world. Extracellular proteins are the earliest
      proteins that come in contact with the host and have a role in the infection
      process. Exoproteins of A. flavus isolated from infected cornea, sputum and a
      saprophyte were pooled and identified using high resolution mass spectrometry in
      order to get the total exoproteome from cultures isolated from different sources.
      A total of 637 proteins was identified from the pooled A. flavus exoproteome.
      Analysis based on GO annotations of the 637 identified proteins revealed that
      hydrolases form the predominant class of proteins in the exoproteome.
      Interestingly, a greater proportion of the exoproteins seem to be secreted
      through the non-classical pathways. This data represent the first in-depth
      analysis of the representative A. flavus exoproteome of a large set of isolates
      from distinct sources. This data have been deposited to the ProteomeXchange with
      identifier PXD001296. 

PMID- 26217705
TI  - Proteomic and microRNA data clarifying the effects of telomere shortening on
      cancer cells.
AB  - In a previous study, we have shown that shortening of telomeres by telomerase
      inhibition sensitized cancer cells to cisplatinum, slower their migration,
      increased DNA damage and impaired DNA repair [1]. In the following study, we
      present a network model combining microRNA and proteomic profiling attempting to
      decipher the molecular mechanism underlying the effect of shortened telomeres on
      the obtained phenotype of cancer cells [2]. The microRNA and proteomic data were
      used for a network model construction, which provided us with several nodal
      candidates that may potentially mediate the shortened-telomeres dependent
      features. These protein expressions were experimentally validated, supporting
      their potential central role in this system [2]. In this article, we delineate
      the full proteomic data and a microarray analyses performed on cells with
      shortened telomeres compared to their cognate parental intact telomere cells. The
      data is attached as excel files. In principle, clarifying the mechanism behind
      telomere shortened phenotype may facilitate novel therapeutics development and
      may also obviate the time consuming process of telomere shortening achieved by
      telomerase inhibition. 

PMID- 26217706
TI  - An endogenous 'non-specific' protein detected by a His-tag antibody is human
      transcription regulator YY1.
AB  - Histidine-tags have been used for a wide variety of experiments including protein
      purification, Western blots, immunoprecipitation and immunohistochemistry. In our
      previous studies, we have repeatedly detected a 'non-specific' endogenous protein
      of about 60 kD in Western blots of protein lysates from HEK293T or HeLa cells
      using the anti-His-tag antibody (His-probe (H3), catalogue #, SC-8036, Santa Cruz
      Biotech. Co.) (Yu et al., J. Biol. Chem. 284 (2009) 1505-1513). Here we have
      immunoprecipitated the protein from HeLa nuclear extracts using the anti-His-tag
      antibody, excised the 60 kD band and subjected it to LC-MS/MS (Fig. 1). The
      deduced sequences of two peptides of the protein match the human transcriptional
      regulator YY1 (Yin and Yang 1, UniProt ID, P25490, Fig. 2), which contains 11
      histidine residues in a stretch (from amino acid 70 to 80) at its NH2-terminal
      region without known functions (Lee et al., Nucleic Acids Res. 23 (1995) 925-931;
      Bushmeyer et al., J. Biol. Chem. 270 (1995) 30213-30220). Since genes encoding
      other Histidine-repeat proteins also exist in the genome (Salichs et al., PLoS
      Genet. 5 (2009) e1000397), it is possible that YY1 might not be the only
      endogenous protein that could be expressed and recognized by the antibody in
      different sources of samples in future experiments. The presence of various
      endogenous histidine-repeat proteins suggests that data from experiments
      particularly immunostaining using His-tag antibodies need to be interpreted with
      caution. This might also be useful to the broader scientific community by
      providing an example for the interpretation of 'non-specific' bands in Western
      blots. 

PMID- 26217707
TI  - Shoot transcriptome of the giant reed, Arundo donax.
AB  - The giant reed, Arundo donax, is a perennial grass species that has become an
      invasive plant in many countries. Expansive stands of A. donax have significant
      negative impacts on available water resources and efforts are underway to
      identify biological control agents against this species. The giant reed grows
      under adverse environmental conditions, displaying insensitivity to drought
      stress, flooding, heavy metals, salinity and herbaceous competition, thus
      hampering control programs. To establish a foundational molecular dataset, we
      used an llumina Hi-Seq protocol to sequence the transcriptome of actively growing
      shoots from an invasive genotype collected along the Rio Grande River, bordering
      Texas and Mexico. We report the assembly of 27,491 high confidence transcripts
      (>=200 bp) with at least 70% coverage of known genes in other Poaceae species. Of
      these 13,080 (47.58%), 6165 (22.43%) and 8246 (30.0%) transcripts have sequence
      similarity to known, domain-containing and conserved hypothetical proteins,
      respectively. We also report 75,590 low confidence transcripts supported by both
      trans-ABBySS and Velvet-Oases de novo assembly pipelines. Within the low
      confidence subset of transcripts we identified partial hits to known (19,021;
      25.16%), domain-containing (7093; 9.38%) and conserved hypothetical (16,647;
      22.02%) proteins. Additionally 32,829 (43.43%) transcripts encode putative
      hypothetical proteins unique to A. donax. Functional annotation resulted in 5,550
      and 6,070 transcripts with assigned Gene Ontology and KEGG pathway information,
      respectively. The most abundant KEGG pathways are spliceosome, ribosome,
      ubiquitin mediated proteolysis, plant-pathogen interaction, RNA degradation and
      oxidative phosphorylation metabolic pathway. Furthermore, we also found 12, 9,
      and 4 transcripts annotated as stress-related, heat stress, and water stress
      proteins, respectively. We envisage that these resources will promote and
      facilitate studies of the abiotic stress capabilities of this exotic plant
      species, which facilitates its invasive capacity. 

PMID- 26217708
TI  - Data set from the phosphoproteomic analysis of Magnaporthe oryzae-responsive
      proteins in susceptible and resistant rice cultivars.
AB  - Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is the most
      destructive disease of rice and causes tremendous losses of rice yield worldwide.
      To explore the molecular mechanisms involved in the rice-M. oryzae interaction,
      we conducted a time-course phosphoproteomic analysis of leaf samples from
      resistant and susceptible rice cultivars infected with M. oryzae. This data
      article contains additional results and analysis of M. oryzae-regulated
      phosphoproteins in rice leaves [1]. We report the analysis of M. oryzae-regulated
      phosphoproteins at all time points, including Venn diagram analysis, close-up
      views, relative intensities, and functional category, and the MS spectra of
      representative phosphoprotein and representative phosphorylated peptides. 

PMID- 26217709
TI  - Data from proteomic characterization and comparison of mammalian milk fat globule
      proteomes by iTRAQ analysis.
AB  - Milk fat globules memebrane (MFGM)-enriched proteomes from Holstein, Jersey, yak,
      buffalo, goat, camel, horse, and human were extracted and identified by an iTRAQ
      quantification proteomic approach. Proteomes data were analyzed by bioinformatic
      and multivariate statistical analysis and used to present the characteristic
      traits of the MFGM proteins among the studied mammals. The data of this study are
      also related to the research article "Proteomic characterization and comparison
      of mammalian milk fat globule proteomes by iTRAQ analysis" in the Journal of
      Proteomics [1]. 

PMID- 26217710
TI  - Tuning the cache memory usage in tomographic reconstruction on standard computers
      with Advanced Vector eXtensions (AVX).
AB  - Cache blocking is a technique widely used in scientific computing to minimize the
      exchange of information with main memory by reusing the data kept in cache
      memory. In tomographic reconstruction on standard computers using vector
      instructions, cache blocking turns out to be central to optimize performance. To
      this end, sinograms of the tilt-series and slices of the volumes to be
      reconstructed have to be divided into small blocks that fit into the different
      levels of cache memory. The code is then reorganized so as to operate with a
      block as much as possible before proceeding with another one. This data article
      is related to the research article titled Tomo3D 2.0 - Exploitation of Advanced
      Vector eXtensions (AVX) for 3D reconstruction (Agulleiro and Fernandez, 2015)
      [1]. Here we present data of a thorough study of the performance of tomographic
      reconstruction by varying cache block sizes, which allows derivation of
      expressions for their automatic quasi-optimal tuning. 

PMID- 26217711
TI  - Systematic pseudopotentials from reference eigenvalue sets for DFT calculations:
      Pseudopotential files.
AB  - We present in this article a pseudopotential (PP) database for DFT calculations
      in the context of the SIESTA code [1-3]. Comprehensive optimized PPs in two
      formats (psf files and input files for ATM program) are provided for 20 chemical
      elements for LDA and GGA exchange-correlation potentials. Our data represents a
      validated database of PPs for SIESTA DFT calculations. Extensive transferability
      tests guarantee the usefulness of these PPs. 

PMID- 26217712
TI  - Data for transcriptome and proteome analysis of Eucalyptus infected with
      Calonectria pseudoreteaudii.
AB  - Cylindrocladium leaf blight is one of the most important diseases in Eucalyptus
      plantations. We investigated the proteome and transcriptome of Eucalyptus
      infected or not infected with Calonectria pseudoreteaudii. Here we provide the
      information about the processing of raw data obtained by RNA-seq and iTRAQ
      technologies. The data are related to [1]. 

PMID- 26217713
TI  - The chicken B-cell line DT40 proteome, beadome and interactomes.
AB  - In developing a new quantitative AP-MS method for exploring interactomes in the
      chicken B-cell line DT40, we also surveyed the most abundant proteins in this
      organism and explored the likely contaminants that bind to a variety of affinity
      resins that would later be confirmed quantitatively [1]. We present the 'Top 150
      abundant DT40 proteins list', the DT40 beadomes as well as protein interaction
      lists for the Phosphatidyl inositol 5-phosphate 4-kinase 2beta and Fanconi
      anaemia protein complexes. 

PMID- 26217714
TI  - Biochemical and computational analyses of two phenotypically related GALT
      mutations (S222N and S135L) that lead to atypical galactosemia.
AB  - Galactosemia is a metabolic disorder caused by mutations in the GALT gene [1,2].
      We encountered a patient heterozygous for a known pathogenic H132Q mutation and a
      novel S222N variant of unknown significance [3]. Reminiscent of patients with the
      S135L mutation, our patient had loss of GALT enzyme activity in erythrocytes but
      a very mild clinical phenotype [3-8]. We performed splicing experiments and
      computational structural analyses to investigate the role of the novel S222N
      variant. Alamut software data predicted loss of splicing enhancers for the S222N
      and S135L mutations [9,10]. A cDNA library was generated from our patient's RNA
      to investigate for splicing errors, but no change in transcript length was seen
      [3]. In silico structural analysis was performed to investigate enzyme stability
      and attempt to understand the mechanism of the atypical galactosemia phenotype.
      Stability results are publicly available in the GALT Protein Database 2.0 [11
      14]. Animations were created to give the reader a dynamic view of the enzyme
      structure and mutation locations. Protein database files and python scripts are
      included for further investigation. 

PMID- 26217715
TI  - Selective transcriptional regulation by Myc: Experimental design and
      computational analysis of high-throughput sequencing data.
AB  - The gene expression programs regulated by the Myc transcription factor were
      evaluated by integrated genome-wide profiling of Myc binding sites, chromatin
      marks and RNA expression in several biological models. Our results indicate that
      Myc directly drives selective transcriptional regulation, which in certain
      physiological conditions may indirectly lead to RNA amplification. Here, we
      illustrate in detail the experimental design concerning the high-throughput
      sequencing data associated with our study (Sabo et al., Nature. (2014) 511:488
      492) and the R scripts used for their computational analysis. 

PMID- 26217716
TI  - CTAB as a soft template for modified clay as filler in active packaging.
AB  - The role of modified clay has been employed in many areas of engineering
      research. Structure of clay was mainly focused on alumino-silicate layer and its
      form was presented as pillar layer. It composed of many ion exchanges inside. In
      industry, in order to use clay with higher efficiency, modification on surface
      and porosity has been developed. CTAB, one of the most effective cationic
      surfactant, was employed to modify the surface and porosity of clay. 

PMID- 26217717
TI  - Collinearity analysis of Brassica A and C genomes based on an updated inferred
      unigene order.
AB  - This data article includes SNP scoring across lines of the Brassica napus TNDH
      population based on Illumina sequencing of mRNA, expanded to 75 lines. The 21,
      323 mapped markers defined 887 recombination bins, representing an updated
      genetic linkage map for the species. Based on this new map, 5 genome sequence
      scaffolds were split and the order and orientation of scaffolds updated to
      establish a new pseudomolecule specification. The order of unigenes and SNP array
      probes within these pseudomolecules was determined. Unigenes were assessed for
      sequence similarity to the A and C genomes. The 57, 246 that mapped to both
      enabled the collinearity of the A and C genomes to be illustrated graphically.
      Although the great majority was in collinear positions, some were not. Analyses
      of 60 such instances are presented, suggesting that the breakdown in collinearity
      was largely due to either the absence of the homoeologue on one genome (resulting
      in sequence match to a paralogue) or multiple similar sequences being present.
      The mRNAseq datasets for the TNDH lines are available from the SRA repository
      (ERA283648); the remaining datasets are supplied with this article. 

PMID- 26217718
TI  - A signature for immune response correlates with HCV treatment outcome in
      Caucasian subjects.
AB  - This data article contains Supplementary material for a published research
      article describing a whole-blood proteomic signature that predicts treatment
      outcome for subjects infected with hepatitis C virus (HCV) [1]. The proteomic
      signature is derived from whole-blood samples from subjects infected with HCV.
      The article includes detailed experimental and computational methods used in the
      analysis. The article also includes tables of demographic and other information
      about the subjects. Finally, the article includes several figures and tables
      showing detailed results of the analyses (e.g. lists of identified proteins and
      coefficients/ROC curves for the regression models). 

PMID- 26217719
TI  - Comparative secretome analysis of rat stomach under different nutritional status.
AB  - The fact that gastric surgery is at the moment the most effective treatment to
      fight against obesity highlights the relevance of gastric derived proteins as
      potential targets to treat this pathology. Taking advantage of a previously
      established gastric explant model for endocrine studies, the proteomic analysis
      of gastric secretome was performed. To validate this gastric explant system for
      proteomic analysis, the identification of ghrelin, a classical gastric derived
      peptide, was performed by MS. In addition, the differential analysis of gastric
      secretomes under differential nutritional status (control feeding vs fasting vs
      re-feeding) was performed. The MS identified proteins are showed in the present
      manuscript. The data supplied in this article is related to the research article
      entitled "Comparative secretome analysis of rat stomach under different
      nutritional status" [1]. 

PMID- 26217720
TI  - Data in support of proteomic and comparative genomic analysis reveal adaptability
      of Brassica napus to phosphorus-deficient stress.
AB  - This data article contains data related to the research article titled proteomic
      and comparative genomic analysis reveal adaptability of Brassica napus to
      phosphorus-deficient stress [1]. Proteome alterations of roots and leaves in two
      B. napus contrasting genotypes, P-efficient 'Eyou Changjia' and P-inefficient
      'B104-2', under long-term low phosphorus (P) and short-term P-free starvation was
      investigated, and then comparative gnomic analysis was conducted to interpret the
      interrelation of the differential abundance protein species responding to P
      deficiency with quantitative trait loci (QTLs) for P deficiency tolerance. The
      report concluded with the results that nearly 50% of the identified protein
      species was mapped in the confidence intervals of QTLs for P efficiency related
      traits. The tables presented here represented the detail information of protein
      spots detected, as well as protein species identified. 

PMID- 26217721
TI  - gamma-tubulin is differentially expressed in mitotic and non-mitotic
      cardiomyocytes in the regenerating zebrafish heart.
AB  - This data article contains complementary figures related to the research article
      entitled, " A dual epimorphic and compensatory mode of heart regeneration" ([10],
      http://dx.doi.org/10.1016/j.ydbio.2014.12.002), which presents a spatial and
      temporal characterization of cardiomyocyte proliferation and dedifferentiation
      after cryoinjury-induced myocardial infarction. This study demonstrated that
      mitotic divisions occur in cardiac cells at distinct differentiation status,
      namely in dedifferentiated cells at the injury border as well as in mature
      cardiac cells within the remaining intact myocardium. One of the important
      aspects supporting our conclusions is a characterization of proteins that are
      upregulated during mitosis in the regenerating hearts. The data presented here
      reveal a dynamic change in the expression level and in the subcellular
      distribution of gamma-tubulin between mitotic and non-mitotic cardiac cells. We
      report that in the non-mitotic cells, gamma-tubulin expression is restricted to
      the centrosome. By contrast, during the mitosis, gamma-tubulin strongly expands
      its localization within the spindle apparatus that interacts with the condensed
      chromosomes. We demonstrated that the differential distribution of gamma-tubulin
      in non-mitotic and mitotic cells requires adjusted image processing for the
      appropriate visualization of both expression patterns in the same histological
      specimens. 

PMID- 26217722
TI  - Data for the characterization of the HSP70 family during osmotic stress in
      banana, a non-model crop.
AB  - Here, we present the data from an in-depth analysis of the HSP70 family in the
      non-model banana during osmotic stress [1]. First, a manual curation of HSP70
      sequences from the banana genome was performed and updated on the Musa hub
      http://banana-genome.cirad.fr/. These curated protein sequences were then
      introduced into our in-house Mascot database for an in-depth look at the HSP70
      protein profiles in banana meristem cultures and roots during osmotic stress. A
      2D-DIGE LC MS/MS approach was chosen to identify and quantify the different
      paralogs and allelic variants in the HSP70 spots. 

PMID- 26217723
TI  - Chemical gas sensor array dataset.
AB  - To address drift in chemical sensing, an extensive dataset was collected over a
      period of three years. An array of 16 metal-oxide gas sensors was exposed to six
      different volatile organic compounds at different concentration levels under
      tightly-controlled operating conditions. Moreover, the generated dataset is
      suitable to tackle a variety of challenges in chemical sensing such as sensor
      drift, sensor failure or system calibration. The data is related to "Chemical gas
      sensor drift compensation using classifier ensembles", by Vergara et al. [1], and
      "On the calibration of sensor arrays for pattern recognition using the minimal
      number of experiments", by Rodriguez-Lujan et al. [2] The dataset can be accessed
      publicly at the UCI repository upon citation of:
      http://archive.ics.uci.edu/ml/datasets/Gas+Sensor+Array+Drift+Dataset+at+Differen
      +Concentrations. 

PMID- 26217724
TI  - Albemarle-Pamlico Sounds revealed and stated preference data.
AB  - In this article we describe the contingent valuation and behavior methods
      scenario developed in the 1995 Albemarle-Pamlico Sounds Survey. The survey
      elicits revealed and stated preference recreation behavior data which are used to
      estimate the value of water quality improvements [4,8]. The survey elicits
      willingness to pay data which are used to conduct a split-sample scope test [7].
      The data are used to jointly estimate revealed and stated preference recreation
      and willingness to pay data [2,6]. The data has been, and can continue to be,
      used to investigate econometric specification [3], bid design and other nonmarket
      valuation issues. The data have been used as illustrations and examples in three
      books that develop nonmarket valuation methods [1,5,9]. Data are supplied with
      this article. 

PMID- 26217725
TI  - Dataset from proteomic analysis of rat, mouse, and human liver microsomes and S9
      fractions.
AB  - Rat, mouse and human liver microsomes and S9 fractions were analyzed using an
      optimized method combining ion exchange fractionation of digested peptides, and
      ultra-high performance liquid chromatography (UHPLC) coupled to high resolution
      tandem mass spectrometry (HR-MS/MS). The mass spectrometry proteomics data have
      been deposited to the ProteomeXchange Consortium
      (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository
      (Vizcaino et al., 2013 [1]) with the dataset identifiers PXD000717, PXD000720,
      PXD000721, PXD000731, PXD000733 and PXD000734. Data related to the peptides
      (trypsin digests only) were also uploaded to Peptide Atlas (Farrah et al., 2013
      [2]) and are available with the dataset identifiers PASS00407, PASS00409,
      PASS00411, PASS00412, PASS00413 and PASS00414. The present dataset is associated
      with a research article published in EuPA Open Proteomics [3]. 

PMID- 26217726
TI  - Data from proteomic analysis of the skin of Chinese giant salamander (Andrias
      davidianus).
AB  - The Chinese giant salamander (Andrias davidianus), renowned as a living fossil,
      is the largest and longest-lived amphibian species in the world. Its skin is rich
      in collagens, and has developed mucous gland which could secrete a large amount
      of mucus under the scraping and electric stimulation. The molting is the degraded
      skin stratum corneum. To establish the functional skin proteome of Chinese giant
      salamander, two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS)
      were applied to detect the composition and relative abundance of the proteins in
      the skin, mucus and molting. The determination of the general proteome in the
      skin can potentially serve as a foundation for future studies characterizing the
      skin proteomes from diseased salamander to provide molecular and mechanistic
      insights into various disease states and potential therapeutic interventions.
      Data presented here are also related to the research article "Proteomic analysis
      of the skin of Chinese giant salamander (Andrias davidianus)" in the Journal of
      Proteomics [1]. 

PMID- 26217727
TI  - Data for a comprehensive map and functional annotation of the human cerebrospinal
      fluid proteome.
AB  - Knowledge about the normal human cerebrospinal fluid (CSF) proteome serves as a
      baseline reference for CSF biomarker discovery and provides insight into CSF
      physiology. In this study, high-pH reverse-phase liquid chromatography (hp-RPLC)
      was first integrated with a TripleTOF 5600 mass spectrometer to comprehensively
      profile the normal CSF proteome. A total of 49,836 unique peptides and 3256 non
      redundant proteins were identified. To obtain high-confidence results, 2513
      proteins with at least 2 unique peptides were further selected as bona fide CSF
      proteins. Nearly 30% of the identified CSF proteins have not been previously
      reported in the normal CSF proteome. More than 25% of the CSF proteins were
      components of CNS cell microenvironments, and network analyses indicated their
      roles in the pathogenesis of neurological diseases. The top canonical pathway in
      which the CSF proteins participated was axon guidance signaling. More than one
      third of the CSF proteins (788 proteins) were related to neurological diseases,
      and these proteins constitute potential CSF biomarker candidates. The mapping
      results can be freely downloaded at http://122.70.220.102:8088/csf/, which can be
      used to navigate the CSF proteome. For more information about the data, please
      refer to the related original article [1], which has been recently accepted by
      Journal of Proteomics. 

PMID- 26217728
TI  - Experimental evidences of the NO action on a recombinant PrxII F from pea plant
      and its effect preventing the citrate synthase aggregation.
AB  - S-nitrosylation is emerging as a key post-translational protein modification for
      the transduction of NO as a signaling molecule in plants. This data article
      supports the research article entitled "Functional and structural changes in
      plant mitochondrial PrxII F caused by NO" [1]. To identify the Cys residues of
      the recombinant PrxII F modified after the treatment with S-nitrosylating agents
      we performed the LC ESI-QTOF tandem MS and MALDI peptide mass fingerprinting
      analysis. Change in A 650 nm was monitored to estimate the thermal aggregation of
      citrate synthase in the presence S-nitrosylated PrxII F. The effect of the
      temperature on the oligomerization pattern and aggregation of PrxII F was
      analysed by SDS-PAGE and changes in absorbance at 650 nm, respectively. 

PMID- 26217729
TI  - Supporting data for comparative proteomic analysis of Listeria monocytogenes ATCC
      7644 exposed to a sublethal concentration of nisin.
AB  - Here we provide the LC-MS/MS data from a comparative analysis of Listeria
      monocytogenes ATCC 7644 treated and non-treated with a sublethal concentration of
      nisin (10(-3) mg/mL). Protein samples were analyzed by multidimensional protein
      identification technology (MudPIT) approach, in an off-line configuration. The
      raw MS/MS data allowed the detection of 49,591 spectra which resulted in 576
      protein identifications. After Scaffold validation, 179 proteins were identified
      with high confidence. A label-free quantitative analysis based of normalized
      spectral abundance factor (NSAF) was used and 13 proteins were found
      differentially expressed between nisin-treated and non-treated cells. Gene
      ontology analysis of differentially expressed proteins revealed that most of them
      are correlated to metabolic process, oxidative stress response mechanisms and
      molecular binding. A detailed analysis and discussion of these data may be found
      in Miyamoto et al. [1]. 

PMID- 26217730
TI  - Data for proteomic analysis of murine cardiomyocytic HL-1 cells treated with
      siRNA against tissue factor.
AB  - This data article is related to the research article entitled Proteomics of
      Tissue Factor silencing in cardiomyocytic cells reveals a new role for this
      coagulation factor in splicing machinery control by Lento et al. [1]. Tissue
      Factor (TF) is a key player in the coagulation cascade, but it has additional
      functions ranging from angiogenesis, tumour invasion and, in the heart, the
      maintenance of the integrity of cardiac cells. This article reports the nano-LC
      MS(E) analysis of the cardiomyocytic HL-1 cell line proteome and describes the
      results obtained from a Gene Ontology analysis of those proteins affected by TF
      gene silencing. 

PMID- 26217731
TI  - Data for transcriptomic and iTRAQ proteomic analysis of Anguilla japonica gills
      in response to osmotic stress.
AB  - This article contains data related to the two research articles titled
      Transcriptomic and iTRAQ proteomic approaches reveal novel short-term
      hyperosmotic stress responsive proteins in the gill of the Japanese eel (Anguilla
      japonica) (Tse et al. [1]) and iTRAQ-based quantitative proteomic analysis
      reveals acute hypo-osmotic responsive proteins in the gills of the Japanese eel
      (Anguilla japonica) (Tse et al. [2]). The two research articles show the
      usefulness of combining transcriptomic and proteomic approaches to provide
      molecular insights of osmoregulation mechanism in a non-model organism, the
      Japanese eel. The information presented here combines the raw data from the two
      studies and provides an overview on the physiological functions of fish gills. 

PMID- 26217732
TI  - Synthetic benchmarks for machine olfaction: Classification, segmentation and
      sensor damage.
AB  - The design of the signal and data processing algorithms requires a validation
      stage and some data relevant for a validation procedure. While the practice to
      share public data sets and make use of them is a recent and still on-going
      activity in the community, the synthetic benchmarks presented here are an option
      for the researches, who need data for testing and comparing the algorithms under
      development. The collection of synthetic benchmark data sets were generated for
      classification, segmentation and sensor damage scenarios, each defined at 5
      difficulty levels. The published data are related to the data simulation tool,
      which was used to create a virtual array of 1020 sensors with a default set of
      parameters [1]. 

PMID- 26217733
TI  - Data set from gas sensor array under flow modulation.
AB  - Recent studies in neuroscience suggest that sniffing, namely sampling odors
      actively, plays an important role in olfactory system, especially in certain
      scenarios such as novel odorant detection. While the computational advantages of
      high frequency sampling have not been yet elucidated, here, in order to motivate
      further investigation in active sampling strategies, we share the data from an
      artificial olfactory system made of 16 MOX gas sensors under gas flow modulation.
      The data were acquired on a custom set up featured by an external mechanical
      ventilator that emulates the biological respiration cycle. 58 samples were
      recorded in response to a relatively broad set of 12 gas classes, defined from
      different binary mixtures of acetone and ethanol in air. The acquired time series
      show two dominant frequency bands: the low-frequency signal corresponds to a
      conventional response curve of a sensor in response to a gas pulse, and the high
      frequency signal has a clear principal harmonic at the respiration frequency. The
      data are related to the study in [1], and the data analysis results reported
      there should be considered as a reference point. The data presented here have
      been deposited to the web site of The University of California at Irvine (UCI)
      Machine Learning Repository
      (https://archive.ics.uci.edu/ml/datasets/Gas+sensor+array+under+flow+modulation).
      The code repository for reproducible analysis applied to the data is hosted at
      the GutHub web site (https://github.com/variani/pulmon). The data and code can be
      used upon citation of [1]. 

PMID- 26217734
TI  - Characterization of the gila monster (Heloderma suspectum suspectum) venom
      proteome.
AB  - The data presented here is related to the research article entitled
      "Characterization of the gila monster (Heloderma suspectum suspectum) venom
      proteome" by Sanggaard et al. in Journal of Proteomics [1]. The gila monster
      venom was collected, analyzed by 2D-gel electrophoresis and after Coomassie
      Brilliant Blue staining the major spots were excised, subjected to in-gel trypsin
      digestion, and analyzed by LC-MS/MS. Subsequently, the venom proteins were
      identified based on de novo sequencing and homology searching. The mass
      spectrometry proteomics data have been deposited to the ProteomeXchange (dataset
      identifier PXD0001343), and in the present article we present an overview of the
      identified proteins. Protein identification failed for three of the selected
      spots, with the method described above. Instead, an iterative process, based on
      de novo sequencing, was employed. 

PMID- 26217735
TI  - Data for in-depth characterisation of the lamb meat proteome from longissimus
      lumborum.
AB  - This Data article provides Supplementary data related to the research article
      titled "In-depth characterisation of the lamb meat proteome from longissimus
      lumborum" by Yu et al. [1]. This research article reports the proteome catalogue
      of the 48 h post-mortem lamb longissimus lumborum. A list of 388 ovine-specific
      proteins were identified and characterised after separating the samples into
      sarcoplasmic, myofibrillar and insoluble fractions, followed by an in-depth
      shotgun proteomic evaluation and bioinformatic analysis. The detailed list of
      identified proteins, the annotated MS/MS spectra corresponding to the proteins
      identified by a single peptide-spectrum match, the raw Gene Ontology annotation
      data and other miscellaneous files, as will be described below, were contained in
      this Data article. We hope the data presented here will contribute to the current
      knowledge of the global protein composition of lamb skeletal muscle/meat. 

PMID- 26217736
TI  - Atmospheric corrosion of metals in industrial city environment.
AB  - Atmospheric corrosion is a significant problem given destruction of various
      materials, especially metals. The corrosion investigation in the industrial city
      environment was carried out during one year exposure. Corrosion potential was
      determined using the potentiometric method. The highest effect of corrosion
      processes was observed during the winter season due to increased air pollution.
      Corrosion of samples pre-treated in tannic acid before the exposure was more
      difficult compared with the samples without pretreatment. The corrosion products
      determined with the SEM/EDS method prove that the most corrosive pollutants
      present in the industrial city air are SO2, CO2, chlorides and dust. 

PMID- 26217737
TI  - Data in support of enhancing metabolomics research through data mining.
AB  - Metabolomics research has evolved considerably, particularly during the last
      decade. Over the course of this evolution, the interest in this 'omic' discipline
      is now more evident than ever. However, the future of metabolomics will depend on
      its capability to find biomarkers. For that reason, data mining constitutes a
      challenging task in metabolomics workflow. This work has been designed in support
      of the research article entitled "Enhancing metabolomics research through data
      mining", which proposed a methodological data handling guideline. An aging
      research in healthy population was used as a guiding thread to illustrate this
      process. Here we provide a further interpretation of the obtained statistical
      results. We also focused on the importance of graphical visualization tools as a
      clue to understand the most common univariate and multivariate data analyses
      applied in metabolomics. 

PMID- 26217738
TI  - Ecological specialization and rarity indices estimated for a large number of
      plant species in France.
AB  - The biological diversity of the Earth is being rapidly depleted due to the direct
      and indirect consequences of human activities. Specialist or rare species are
      generally thought to be more extinction prone than generalist or common species.
      Testing this assumption however requires that the rarity and ecological
      specialization of the species are quantified. Many indices have been developed to
      classify species as generalists vs. specialists or as rare vs. common, but large
      data sets are needed to calculate these indices. Here, we present a list of
      specialization and rarity values for more than 2800 plant species of continental
      France, which were computed from the large botanical and ecological dataset
      SOPHY. Three specialization indices were calculated using species co-occurrence
      data. All three indices are based on (dis)similarity among plant communities
      containing a focal species, quantified either as beta diversity in an additive
      (Fridley et al., 2007 [6]) or multiplicative (Zeleny, 2008 [15]) partitioning of
      diversity or as the multiple site similarity of Baselga et al. (2007) [1].
      Species rarity was calculated as the inverse of a species occurrence. 

PMID- 26217739
TI  - Dataset from chemical gas sensor array in turbulent wind tunnel.
AB  - The dataset includes the acquired time series of a chemical detection platform
      exposed to different gas conditions in a turbulent wind tunnel. The chemo-sensory
      elements were sampling directly the environment. In contrast to traditional
      approaches that include measurement chambers, open sampling systems are sensitive
      to dispersion mechanisms of gaseous chemical analytes, namely diffusion,
      turbulence, and advection, making the identification and monitoring of chemical
      substances more challenging. The sensing platform included 72 metal-oxide gas
      sensors that were positioned at 6 different locations of the wind tunnel. At each
      location, 10 distinct chemical gases were released in the wind tunnel, the
      sensors were evaluated at 5 different operating temperatures, and 3 different
      wind speeds were generated in the wind tunnel to induce different levels of
      turbulence. Moreover, each configuration was repeated 20 times, yielding a
      dataset of 18,000 measurements. The dataset was collected over a period of 16
      months. The data is related to "On the performance of gas sensor arrays in open
      sampling systems using Inhibitory Support Vector Machines", by Vergara et al.[1].
      The dataset can be accessed publicly at the UCI repository upon citation of [1]:
      http://archive.ics.uci.edu/ml/datasets/Gas+sensor+arrays+in+open+sampling+setting
      . 

PMID- 26217740
TI  - Data for iTRAQ secretomic analysis of Aspergillus fumigatus in response to
      different carbon sources.
AB  - Here, we provide data related to the research article entitled "Quantitative
      proteomics study of Aspergillus fumigatus secretome revealed deamidation of
      secretory enzymes" by Adav et al. (J. Proteomics (2015) [1]). Aspergillus sp.
      plays an important role in lignocellulosic biomass recycling. To explore biomass
      hydrolyzing enzymes of A. fumigatus, we profiled secretome under different carbon
      sources such as glucose, cellulose, xylan and starch by high throughput
      quantitative proteomics using isobaric tags for relative and absolute
      quantification (iTRAQ). The data presented here represents the detailed
      comparative abundances of diverse groups of biomass hydrolyzing enzymes including
      cellulases, hemicellulases, lignin degrading enzymes, and peptidases and
      proteases; and their post translational modification like deamidation. 

PMID- 26217741
TI  - The quantum chemical causality of pMHC-TCR biological avidity: Peptide atomic
      coordination data and the electronic state of agonist N termini.
AB  - The quantum state of functional avidity of the synapse formed between a peptide
      Major Histocompatibility Complex (pMHC) and a T cell receptor (TCR) is a subject
      not previously touched upon. Here we present atomic pair correlation meta-data
      based on crystalized tertiary structures of the Tax (HTLV-1) peptide along with
      three artificially altered variants, all of which were presented by the (Class I)
      HLA-A201 protein in complexation with the human (CD8(+)) A6TCR. The meta-data
      reveal the existence of a direct relationship between pMHC-TCR functional avidity
      (agonist/antagonist) and peptide pair distribution function (PDF). In this
      context, antagonist peptides are consistently under-coordinated in respect to
      Tax. Moreover, Density Functional Theory (DFT) datasets in the BLYP/TZ2P level of
      theory resulting from relaxation of the H species on peptide tertiary structures
      reveal that the coordination requirement of agonist peptides is also expressed as
      a physical observable of the protonation state of their N termini: agonistic
      peptides are always found to retain a stable ammonium (NH3 (+)) terminal group
      while antagonist peptides are not. 

PMID- 26217742
TI  - Data in support of comparative analysis of strawberry proteome in response to
      controlled atmosphere and low temperature storage using a label-free
      quantification.
AB  - To elucidate the mechanisms contributing to fruit responses to senescence and
      stressful environmental stimuli under low temperature (LT) and controlled
      atmosphere (CA) storage, a label-free quantitative proteomic investigation was
      conducted in strawberry (Fragaria ananassa, Duch. cv. 'Akihime'). Postharvest
      volatile compounds were characterized following storage under different
      conditions. The observed post-storage protein expression profiles may be
      associated with delayed senescence features in strawberry [2]. A total of 454
      proteins were identified in differentially treated strawberry fruits.
      Quantitative analysis, using normalized spectral counts, revealed 73 proteins
      common to all treatments, which formed three clusters in a hierarchical
      clustering analysis. 

PMID- 26217743
TI  - Data supporting the comparative life cycle assessment of different municipal
      solid waste management scenarios.
AB  - Environmental assessment of municipal solid waste (MSW) management scenarios
      would help to select eco-friendly scenarios. In this study, the inventory data in
      support of life cycle assessment of different MSW are presented. The scenarios
      were defined as: anaerobic digestion (AD, Sc-0), landfilling combined with
      composting (Sc-1), incineration (Sc-2), incineration combined with composting (Sc
      3), and AD combined with incineration (Sc-4). The current article contains
      flowcharts of the different scenarios. Additionally, six supplementary files
      including inventory data on the different scenarios, data on the different damage
      assessment categories, normalization, and single scores are presented
      (Supplementary files 1-6). The analysis of the different scenarios revealed that
      the most eco-friendly scenario to be implemented in the future would be the
      combination of AD and incineration (Sc-4). 

PMID- 26217744
TI  - Data in support of dual-functionalized cellulose nanofibrils prepared through
      TEMPO-mediated oxidation and surface-initiated ATRP.
AB  - We previously studied a suitably 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)
      oxidized cellulose nanofibrils (TOCNs) that can be further functionalized with
      initiating sites and overcame the obstacle of performing atom transfer radical
      polymerization (ATRP) in the presence of neutral carboxylic acid sodium salt
      groups [1]. Herein, characterization of the modified TOCNs and of the products
      from surface-initiated (SI) ATRP of the (nano)celluloses with styrene (St) was
      performed using nuclear magnetic resonance (NMR), gel permeation chromatography
      (GPC), and contact angle (CA) measurements. From the analysis of (1)H NMR, a high
      purity of sacrificial initiator (i.e., 2-hydroxyethyl 2-bromoisobutyrate (HEBiB))
      was confirmed. HEBiB was utilized to trace the SI ATRP with the generated free
      PSt. Gradually molecular weight evaluations were revealed from GPC analysis (ca.
      M n=21,000 and D=1.10) using different TOCNs, implying the insignificant
      contribution to the kinetics from the grafted initiating sites. The TOCN-g-PSts
      were further characterized by contact angles and displayed an obvious
      reversibility between hydrophilicity and hydrophobicity in tens of minutes. These
      results illustrated a simple and facile approach for controlling the graft length
      and composition of TOCNs through SI ATRP. 

PMID- 26217745
TI  - Optical modelling data for room temperature optical properties of organic
      inorganic lead halide perovskites.
AB  - The optical properties of perovskites at ambient temperatures are important both
      to the design of optimised solar cells as well as in other areas such as the
      refinement of electronic band structure calculations. Limited previous
      information on the optical modelling has been published. The experimental fitting
      parameters for optical constants of CH3NH3PbI3-x Cl x and CH3NH3PbI3 perovskite
      films are reported at 297 K as determined by detailed analysis of reflectance and
      transmittance data. The data in this study is related to the research article
      "Room temperature optical properties of organic-inorganic lead halide
      perovskites" in Solar Energy Materials & Solar Cells [1]. 

PMID- 26217746
TI  - Impact of twin boundaries on bulk elastic constants: Density-functional theory
      data for Young's modulus of Ag.
AB  - Experimental and theoretical studies on nanowires have reported a size-dependence
      of the Young's modulus in the axial direction, which has been attributed to the
      increasing influence of surface stresses with decreasing wire diameter. Internal
      interfaces and their associated interface stresses could lead to similar changes
      in the elastic properties. In Kobler et al. [1], however, we reported results
      from atomistic calculations which showed for Ag that twin boundaries have a
      negligible effect on the Young's modulus. Here, we present data of density
      functional theory calculations of elastic constants and Young's modulus for
      defect-free bulk Ag as well as for bulk Ag containing dense arrays of twin
      boundaries. It is shown that rigorous convergence tests are required in order to
      be able to deduce changes in the elastic properties due to bulk defects in a
      reliable way. 

PMID- 26217747
TI  - Data set from chemical sensor array exposed to turbulent gas mixtures.
AB  - A chemical detection platform composed of 8 chemo-resistive gas sensors was
      exposed to turbulent gas mixtures generated naturally in a wind tunnel. The
      acquired time series of the sensors are provided. The experimental setup was
      designed to test gas sensors in realistic environments. Traditionally, chemical
      detection systems based on chemo-resistive sensors include a gas chamber to
      control the sample air flow and minimize turbulence. Instead, we utilized a wind
      tunnel with two independent gas sources that generate two gas plumes. The plumes
      get naturally mixed along a turbulent flow and reproduce the gas concentration
      fluctuations observed in natural environments. Hence, the gas sensors can capture
      the spatio-temporal information contained in the gas plumes. The sensor array was
      exposed to binary mixtures of ethylene with either methane or carbon monoxide.
      Volatiles were released at four different rates to induce different concentration
      levels in the vicinity of the sensor array. Each configuration was repeated 6
      times, for a total of 180 measurements. The data is related to "Chemical
      Discrimination in Turbulent Gas Mixtures with MOX Sensors Validated by Gas
      Chromatography-Mass Spectrometry", by Fonollosa et al. [1]. The dataset can be
      accessed publicly at the UCI repository upon citation of [1]:
      http://archive.ics.uci.edu/ml/datasets/Gas+senso+rarray+exposed+to+turbulent+gas+
      ixtures. 

PMID- 26217748
TI  - pI-Control in Comparative Fluorescence Gel Electrophoresis (CoFGE) using
      amphoteric azo dyes.
AB  - Amphoteric azo dyes were used for internal control of pI values in Comparative
      two-dimensional Fluorescence Gel Electrophoresis (CoFGE) [1]. The 2D-gel images
      of separated Escherichia coli proteins as well as those of colored amphoteric
      dyes separated by isoelectric focussing are presented. The latter were used to
      correct for variation in the first electrophoretic dimension and further improve
      protein coordinate assignment in 2D-gel electrophoresis. Data tables are supplied
      to demonstrate pI-value calibration and the effect on the assignment of protein
      spot coordinates. 

PMID- 26217749
TI  - Dynamics of hepatic gene expression and serum cytokine profiles in single and
      double-hit burn and sepsis animal models.
AB  - We simulate the pathophysiology of severe burn trauma and burn-induced sepsis,
      using rat models of experimental burn injury and cecal ligation and puncture
      (CLP) either individually (singe-hit model) or in combination (double-hit model).
      The experimental burn injury simulates a systemic but sterile pro-inflammatory
      response, while the CLP simulates the effect of polymicrobial sepsis. Given the
      liver's central role in mediating the host immune response and onset of
      hypermetabolism after burn injury, elucidating the alterations in hepatic gene
      expression in response to injury can lead to a better understanding of the
      regulation of the inflammatory response, whereas circulating cytokine protein
      expression, reflects key systemic inflammatory mediators. In this article, we
      present both the hepatic gene expression and circulating cytokine/chemokine
      protein expression data for the above-mentioned experimental model to gain
      insights into the temporal dynamics of the inflammatory and hypermetabolic
      response following burn and septic injury. This data article supports results
      discussed in research articles (Yang et al., 2012 [1,4]; Mattick et al. 2012,
      2013 [2,3]; Nguyen et al., 2014 [5]; Orman et al., 2011, 2012 [6-8]). 

PMID- 26217751
TI  - NMR spectra and electrochemical behavior of catechol-bearing block copolymer
      micelles.
AB  - Here, we provide the NMR spectra and AFM data for antioxidant micelles prepared
      from amphiphilic PAM-PDA block copolymers composed of a poly(N-acryloyl
      morpholine) and a redox-active catechol-bearing block with different catechol
      content. We also provide details of the electrochemical analysis that showed
      micelles higher catechol content had a similar redox potential with the small
      catechol compound dopamine, but slowed down the redox reaction (Hasegawa et al.,
      Polymer (in press)). 

PMID- 26217750
TI  - Quantitative proteomics of rat and human pancreatic beta cells.
AB  - Data set description: This data set is composed by label-free alternate-scanning
      LC-MS/MS proteomics analysis human and Wistar rat pancreatic islet endocrine
      cells. The mass spectrometry data of the human and rat pancreatic beta cells and
      the resulting proteome search output from ProteinLynx GlobalSERVER (PLGS) have
      been deposited to the ProteomeXchange Consortium [1] via the PRIDE partner
      repository with the dataset identifiers PXD001539 (human) and PXD001816 (rat).
      From these mass spectrometry data, 'relative molar amount units' between cell
      types and across species were calculated. Biological relevance: These data
      provide a quantitative view on the unfractionated proteomes of human and rat beta
      and alpha cells. It is likely biased towards the proteins with higher molar
      abundance, relating to core functional pathways, but also includes several
      proteins with an islet-enriched expression. The quality of the cell preps is
      state-of-the-art, and the label-free quantitation is both precise and accurate,
      allowing detailed quantitative analysis. 

PMID- 26217752
TI  - Data in support of protocol for rat single muscle-fiber isolation and culture.
AB  - This data article contains data related to the research article entitled,
      "Protocol for rat single muscle-fiber isolation and culture" by Komiya et al.
      [1]. It has yet to be shown whether adult myosin heavy chain (MyHC) isoforms are
      expressed at a readily detectable level in cultured myotubes. In this study, we
      examined whether adult MyHC isoforms could be detected in myotubes differentiated
      from rat satellite cells using a Western blotting assay and specific antibodies
      against slow MyHC, fast MyHC and pan-MyHC. Results showed that slow adult MyHC
      isoforms were faintly detected in myotubes, suggesting that rat myotubes express
      adult MyHC isoforms although that amount is very low. 

PMID- 26217753
TI  - Data set for Tifinagh handwriting character recognition.
AB  - The Tifinagh alphabet-IRCAM is the official alphabet of the Amazigh language
      widely used in North Africa [1]. It includes thirty-one basic letter and two
      letters each composed of a base letter followed by the sign of labialization.
      Normalized only in 2003 (Unicode) [2], ICRAM-Tifinagh is a young character
      repertoire. Which needs more work on all levels. In this context we propose a
      data set for handwritten Tifinagh characters composed of 1376 image; 43 Image For
      Each character. The dataset can be used to train a Tifinagh character recognition
      system, or to extract the meaning characteristics of each character. 

PMID- 26217754
TI  - Data in support of quantification of pyrophosphate as a universal approach to
      determine polymerase activity and assay polymerase inhibitors.
AB  - Characterization of synthetic oligonucleotides and quantification of primer
      extension mediated by a human translesion synthesis polymerase eta (Pol eta) over
      drug-induced DNA lesions in the presence on modified nucleotide analogs is
      described. Extent of primer extension for each reaction was monitored by
      denaturing gel electrophoresis. The data was obtained to assess the performance
      of the fluorescence-based primer extension (PE-PiPer) assay [1] with respect to
      the established and conventionally used denaturing gel electrophoresis. The
      obtained data reflects the specific inhibition of translesion synthesis over
      cisplatin containing DNA with 5-OH-CTP. 

PMID- 26217755
TI  - A calibration curve for immobilized dihydrofolate reductase activity assay.
AB  - An assay was developed for measuring the active-site concentration, activity, and
      thereby the catalytic turnover rate (k cat) of an immobilized dihydrofolate
      reductase model system (Singh et al., (2015), Anal. Biochem). This data article
      contains a calibration plot for the developed assay. In the calibration plot rate
      is plotted as a function of DHFR concentration and shows linear relationship. The
      concentration of immobilized enzyme was varied by using 5 different size mica
      chips. The dsDNA concentration was the same for all chips, assuming that the
      surface area of the mica chip dictates the resulting amount of bound enzyme (i.e.
      larger sized chip would have more bound DHFR). The activity and concentration of
      each chip was measured. 

PMID- 26217756
TI  - ATP4 and ciliation in the neuroectoderm and endoderm of Xenopus embryos and
      tadpoles.
AB  - During gastrulation and neurulation, foxj1 expression requires ATP4a-dependent
      Wnt/beta-catenin signaling for ciliation of the gastrocoel roof plate (Walentek
      et al. Cell Rep. 1 (2012) 516-527.) and the mucociliary epidermis (Walentek et
      al. Dev. Biol. (2015)) of Xenopus laevis embryos. These data suggested that ATP4a
      and Wnt/beta-catenin signaling regulate foxj1 throughout Xenopus development.
      Here we analyzed whether foxj1 expression was also ATP4a-dependent in other
      ciliated tissues of the developing Xenopus embryo and tadpole. We found that in
      the floor plate of the neural tube ATP4a-dependent canonical Wnt signaling was
      required for foxj1 expression, downstream of or in parallel to Hedgehog
      signaling. In the developing tadpole brain, ATP4-function was a prerequisite for
      the establishment of cerebrospinal fluid flow. Furthermore, we describe foxj1
      expression and the presence of multiciliated cells in the developing tadpole
      gastrointestinal tract. Our work argues for a general requirement of ATP4
      dependent Wnt/beta-catenin signaling for foxj1 expression and motile ciliogenesis
      throughout Xenopus development. 

PMID- 26217757
TI  - High resolution 3D laboratory x-ray tomography data of femora from young, 1-14
      day old C57BL/6 mice.
AB  - This data article contains high resolution (1.2 um effective pixel size) lab
      based micro-computed tomography (uCT) reconstructed volume data of the femoral
      mid-shafts from young C57BL/6 mice. This data formed the basis for the analyses
      of bone structural development in healthy mice, including closed and open
      porosity as reported in Bortel et al. [1]. The data reveals changes seen in bone
      material and porosity distribution observed when mouse bones transform from
      porous scaffolds into solid structures during normal organogenesis. 

PMID- 26217758
TI  - Core-shell grain structures and ferroelectric properties of Na0.5K0.5NbO3-LiTaO3
      BiScO3 piezoelectric ceramics.
AB  - Legislation arising from health and environmental concerns has intensified
      research into finding suitable alternatives to lead-based piezoceramics.
      Recently, solid solutions based on sodium potassium niobate (K,Na)NbO3 (KNN) have
      become one of the globally-important lead-free counterparts, due to their
      favourable dielectric and piezoelectric properties. This data article provides
      information on the ferroelectric properties and core-shell grain structures for
      the system, (1-y)[(1-x)Na0.5K0.5NbO3 - xLiTaO3] - yBiScO3 (x=0-0.1, y=0.02,
      abbreviated as KNN-xLT-2BS). We show elemental analysis with aid of TEM spot-EDX
      to identify three-type grain-types in the KNN-LT-BS ternary system. Melting
      behaviour has been assessed using a tube furnace with build-in camera. Details
      for the ferroelectric properties and core-shell chemical segregation are
      illustrated. 

PMID- 26217759
TI  - Important mitochondrial proteins in human omental adipose tissue show reduced
      expression in obesity.
AB  - Obesity is associated with impaired mitochondrial function. This study compares
      mitochondrial protein expression in omental fat in obese and non-obese humans.
      Omental adipose tissue was obtained by surgical biopsy, adipocytes were purified
      and mitochondria isolated. Using anion-exchange chromatography, SDS-PAGE and mass
      spectrometry, 128 proteins with potentially different abundances in patient
      groups were identified, 62 of the 128 proteins are mainly localized in the
      mitochondria. Further quantification of 12 of these 62 proteins by immune dot
      blot analysis revealed four proteins citrate synthase, HADHA, LETM1 and mitofilin
      being inversely associated with BMI, and mitofilin being inversely correlated
      with gender. 

PMID- 26217760
TI  - Two-dimensional gel electrophoresis data in support of leaf comparative
      proteomics of two citrus species differing in boron-tolerance.
AB  - Here, we provide the data from a comparative proteomics approach used to
      investigate the response of boron (B)-tolerant 'Xuegan' (Citrus sinensis) and B
      intolerant 'Sour pummelo' (Citrus grandis) leaves to B-toxicity. Using two
      dimensional gel electrophoresis (2-DE) technique, we identified 50 and 45 protein
      species with a fold change of more than 1.5 and a P-value of less than 0.05 from
      B-toxic C. sinensis and C. grandis leaves. These B-toxicity-responsive protein
      species were mainly involved in carbohydrate and energy metabolism, antioxidation
      and detoxification, stress responses, coenzyme biosynthesis, protein and amino
      acid metabolism, signal transduction, cell transport, cytoskeleton, nucleotide
      metabolism, and cell cycle and DNA processing. A detailed analysis of this data
      may be obtained from Sang et al. (J. Proteomics 114 (2015))[1]. 

PMID- 26217761
TI  - Genome-wide transcriptional profiling data from skin of chronic cutaneous lupus
      erythematosus (CCLE) patients.
AB  - Cutaneous features manifest as a wide range of clinically significant, and in
      many cases disfiguring and debilitating components of lupus erythematosus (LE).
      While the definitive etiology is in question, multifactorial and polygenic causes
      are likely to be involved in the production of the characteristic anti-nuclear
      autoantibody titers and immune cell infiltrates observed in chronic cutaneous LE
      (CCLE) [1-3]. There is significant overlap of patients with systemic and
      cutaneous manifestations of LE, which suggests shared pathways and genetic
      background between the two. We have employed genome-wide microarray technology
      along with pathway-based analyses to investigate transcriptional differences
      between lesional and non-lesional skin from CCLE patients to address existing
      gaps in knowledge regarding disease mechanisms in lupus [4]. 

PMID- 26217762
TI  - Data in support of global role of the membrane protease LonB in Archaea:
      Potential protease targets revealed by quantitative proteome analysis of a lonB
      mutant in Haloferax volcanii.
AB  - This data article provides information in support of the research article "Global
      role of the membrane protease LonB in Archaea: Potential protease targets
      revealed by quantitative proteome analysis of a lonB mutant in Haloferax
      volcanii" [1]. The proteome composition of a wt and a LonB protease mutant strain
      (suboptimal expression) in the archaeon Haloferax volcanii was assessed by a
      quantitative shotgun proteomic approach. Membrane and cytosol fractions of H.
      volcanii strains were examined at two different growth stages (exponential and
      stationary phase). Data is supplied in the present article. This study represents
      the first proteome examination of a Lon-deficient cell of the Archaea Domain. 

PMID- 26217763
TI  - Data in support of 5'AMP-activated protein kinase alpha regulates stress granule
      biogenesis.
AB  - This data article contains insights into the regulation of cytoplasmic stress
      granules (SGs) by 5'-AMP-activated kinase (AMPK). Our results verify the specific
      association of AMPK-alpha2, but not AMPK-alpha1, with SGs. We also provide
      validation data for the isoform-specific recruitment of the AMPK-alpha subunit to
      SGs using (i) different antibodies and (ii) a distinct cellular model system. In
      addition, we assess the SG association of the regulatory AMPK beta- and gamma
      subunits. The interpretation of these data and further extensive insights into
      the regulation of SG biogenesis by AMPK can be found in "5'AMP-activated protein
      kinase alpha regulates stress granule biogenesis" [1]. 

PMID- 26217764
TI  - Phospho-iTRAQ data article: Assessing isobaric labels for the large-scale study
      of phosphopeptide stoichiometry.
AB  - The ability to distinguish between phosphopeptides of high and low stoichiometry
      is essential to discover the true extent of protein phosphorylation. We here
      extend the strategy whereby a peptide sample is briefly split in two identical
      parts and differentially labeled preceding the phosphatase treatment of one part
      (Pflieger et al., 2008. Mol. Cell. Proteomics, 7: 326-46 [1]; Wu et al., 2011.
      Nat. Methods, 8: 677-83 [2]). Our Phospho-iTRAQ method focuses on the unmodified
      counterparts of phosphorylated peptides, which thus circumvents the ionization,
      fragmentation, and phospho-enrichment difficulties that hamper quantitation of
      stoichiometry in most common phosphoproteomics methods. Since iTRAQ enables
      multiplexing, simultaneous (phospho)proteome comparison between internal
      replicates and multiple samples is possible. The technique was validated on
      multiple instrument platforms by adding internal standards of high stoichiometry
      to a complex lysate of control and EGF-stimulated HeLa cells. To demonstrate the
      flexibility of PhosphoiTRAQ with regards to the experimental setup and data
      mining, the proteome coverage was extended through gel fractionation, while an
      internal replicate measurement creates more stringent data analysis
      opportunities. The latter allows other researchers to set their own threshold for
      selecting potential phosphorylation events in the dataset presented here,
      depending on the biological question or corroboration under investigation. The
      latest developments in MS instrumentation promise to further increase the
      resolution of the stoichiometric measurement of Phospho-iTRAQ in the future. The
      data accompanying the manuscript on this approach (Glibert et al., 2015, J.
      Proteome Res. 14: 2015, 839-49 [5]) have been deposited to the ProteomeXchange
      with identifier PXD001574. 

PMID- 26217765
TI  - Synthesis of biotinylated probes of artemisinin for affinity labeling.
AB  - In this data article, we described the synthetic routes to four biotinylated
      probes (2, 3, 4, and 5) of artemisinin and the associated experimental
      procedures. We also provided the physical data for the synthesized compounds.
      These synthesized biotinylated probes of artemisinin are useful molecular tools
      for the affinity-labeling study of target receptor proteins of artemisinin in
      tropical pathogens such as Trypanosoma, Leishmania, and Schistosoma. The data
      provided herein are related to "Biotinylated probes of artemisinin with labeling
      affinity toward Trypanosoma brucei brucei target proteins", by Konziase (Anal.
      Biochem. (2015)). 

PMID- 26217766
TI  - Polymerase chain reaction-based gene removal from plasmids.
AB  - This data article contains supplementary figures and methods to the research
      article entitled, "Multiplex gene removal by two-step polymerase chain reactions"
      (Krishnamurthy et al., Anal. Biochem., 2015,
      doi:http://dx.doi.org/10.1016/j.ab.2015.03.033), which presents a restriction
      enzyme free method to remove multiple DNA segments from plasmids. Restriction
      free cloning methods have dramatically improved the flexibility and speed of
      genetic manipulation compared to conventional assays based on restriction enzyme
      digestion (Lale and Valla, 2014. DNA Cloning and Assembly Methods, vol. 1116).
      Here, we show the basic scheme and characterize the success rate for single and
      multiplex gene removal from plasmids. In addition, we optimize experimental
      conditions, including the amount of template, multiple primers mixing, and
      buffers for DpnI treatment, used in the one-pot reaction for multiplex gene
      removal. 

PMID- 26217767
TI  - 24-hour human urine and serum profiles of bisphenol A following ingestion in
      soup: Individual pharmacokinetic data and emographics.
AB  - Here we present data to evaluate potential absorption of Bisphenol A through non
      metabolizing tissues of the upper digestive tract. Concurrent serum and urine
      concentrations of d6-BPA, and its glucuronide and sulfate conjugates, were
      measured over a 24 h period in 10 adult male volunteers following ingestion of 30
      MUg d6-BPA/kg body weight in soup. The pharmacokinetic behavior of BPA and its
      metabolites in this cohort (rapid absorption, complete elimination, evidence
      against sublingual absorption) was reported. This Data in Brief article contains
      the corresponding individual pharmacokinetic data, reports the demographics of
      the cohort and provides additional details related to the analytical methods
      employed and is related to [4]. 

PMID- 26217768
TI  - Benchmark data for identifying DNA methylation sites via pseudo trinucleotide
      composition.
AB  - This data article contains three benchmark datasets for training and testing iDNA
      Methyl, a web-server predictor for identifying DNA methylation sites [Liu et al.
      Anal. Biochem. 474 (2015) 69-79]. 

PMID- 26217769
TI  - Data from identification of diagnostic biomarkers and metabolic pathway shifts of
      heat-stressed lactating dairy cows.
AB  - Controlling heat stress (HS) is a global challenge for the dairy industry. In
      this work, an integrated metabolomics and lipidomics approach using (1)H nuclear
      magnetic resonance (NMR) and ultra-fast LC-MS in combination with multivariate
      analyses was employed to investigate the discrimination of plasma metabolic
      profiles between HS-free and HS lactating dairy cows. Here we provide the
      information about the acquiring and processing of raw data obtained by (1)H NMR
      and LC-MS techniques. The data of present study are related to the research
      article "Identification of diagnostic biomarkers and metabolic pathway shifts of
      heat-stressed lactating dairy cows" in the Journal of Proteomics (Tian et al., J.
      Proteomics, (2015), doi:10.1016/j.jprot.2015.04.014). 

PMID- 26217770
TI  - Lipopolysaccharide induced MAP kinase activation in RAW 264.7 cells attenuated by
      cerium oxide nanoparticles.
AB  - High mortality rates are associated with the life threatening disease of sepsis.
      Improvements in septic patient survivability have failed to materialize with
      currently available treatments. This article represents data regarding a study
      published in biomaterials (Vellaisamy et al., Biomaterials, 2015, in press). with
      the purpose of evaluating whether severe sepsis mortality and associated hepatic
      dysfunction induced by lipopolysaccharide (LPS) can be prevented by cerium oxide
      nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide
      the information about the method and processing of raw data related to our study
      publish in Biomaterials and Data in Brief (Vellaisamy et al., Biomaterials, 2015,
      in press; Vellaisamy et al., Data in Brief, 2015, in press.). The data contained
      in this article evaluates the contribution of MAPK signaling in LPS induced
      sepsis. Macrophage cells (RAW 264.7) were treated with a range of cerium oxide
      nanoparticle concentration in the presence and absence of LPS. Immunoblotting was
      performed on the cell lysates to evaluate the effect of cerium oxide nanoparticle
      treatment on LPS induced changes in Mitogen Activated Protein Kinases (MAPK) p
      38, ERK 1/2, and SAPK/JNK phosphorylation. 

PMID- 26217771
TI  - Quantification of proteome changes in bovine muscle from two-dimensional
      electrophoresis data.
AB  - Proteome changes in the longissimus thoracis bovine muscle in response to pre
      slaughter stress were assessed on the basis of two-dimensional electrophoresis (2
      DE) data. In this study, the bootstrap resampling statistical technique and a new
      measure of relative change of the volume of 2-DE protein spots are shown to be
      more efficient than commonly used statistics to reliably quantify changes in
      protein abundance in stress response. The data are supplied in this article and
      are related to "Tackling proteome changes in the longissimus thoracis bovine
      muscle in response to pre-slaughter stress" by Franco et al. [1]. 

PMID- 26217772
TI  - Cerium oxide nanoparticles inhibit lipopolysaccharide induced MAP kinase/NF-kB
      mediated severe sepsis.
AB  - The life threatening disease of sepsis is associated with high mortality. Septic
      patient survivability with currently available treatments has failed to improve.
      The purpose of this study was to evaluate whether lipopolysaccharide (LPS)
      induced sepsis mortality and associated hepatic dysfunction can be prevented by
      cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here
      we provide the information about the methods processing of raw data related to
      our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In
      press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The
      data present here provides confirmation of cerium oxide nanoparticle treatments
      ability to prevent the LPS induced sepsis associated changes in physiological,
      blood cell count, inflammatory protein and growth factors in vivo. In vitro
      assays investigation the treated of macrophages cells with different
      concentrations of cerium oxide nanoparticle demonstrate that concentration of
      cerium oxide nanoparticles below 1 ug/ml did not significantly influence cell
      survival as determined by the MTT assay. 

PMID- 26217773
TI  - Three-dimensional morphology of the human embryonic brain.
AB  - The morphogenesis of the cerebral vesicles and ventricles was visualized in 3D
      movies using images derived from human embryo specimens between Carnegie stage 13
      and 23 from the Kyoto Collection. These images were acquired with a magnetic
      resonance microscope equipped with a 2.35-T superconducting magnet. Three
      dimensional images using the same scale demonstrated brain development and growth
      effectively. The non-uniform thickness of the brain tissue, which may indicate
      brain differentiation, was visualized with thickness-based surface color mapping.
      A closer view was obtained of the unique and complicated differentiation of the
      rhombencephalon, especially with regard to the internal view and thickening of
      the brain tissue. The present data contribute to a better understanding of brain
      and cerebral ventricle development. 

PMID- 26217774
TI  - Data set for cloning and characterization of heterologous transporters in
      Saccharomyces cerevisiae and identification of important amino acids for xylose
      utilization.
AB  - The efficient uptake is important for the xylose utilization by Saccharomyces
      cerevisiae. A heterogenous transporter Mgt05196p was cloned from Meyerozyma
      guilliermondii and expressed in Saccharomyces cerevisiae[1]. This data article
      contains the transport characteristics of Mgt05196p in S. cerevisiae. The
      fluorescence of fusion protein Mgt05196p-GFP expressing strain was located on the
      cell surface demonstrated that the heterogenous transporter Mgt05196p was
      targeted to the plasma membrane of S. cerevisiae. The expressing of Mgt05196p in
      the hxt null S. cerevisiae endowed the strain with the glucose and d-xylose
      absorption capacity, as well as expressing the native d-xylose transporter Gal2p.
      The transmembrane domains of Mgt05196p were predicted and compared with the
      XylEp, whose crystal structure was revealed. And then, the homologous modeling of
      Mgt05196p was built basing on the XylEp to find out the crucial amino acid
      residues for sugars binding and transport. 

PMID- 26217775
TI  - Data for mitochondrial proteomic alterations in the aging mouse brain.
AB  - Mitochondria are dynamic organelles critical for many cellular processes,
      including energy generation. Thus, mitochondrial dysfunction likely plays a role
      in the observed alterations in brain glucose metabolism during aging. Despite
      implications of mitochondrial alterations during brain aging, comprehensive
      quantitative proteomic studies remain limited. Therefore, to characterize the
      global age-associated mitochondrial proteomic changes in the brain, we analyzed
      mitochondria isolated from the brain of 5-, 12-, and 24-month old mice using
      quantitative mass spectrometry. We identified changes in the expression of
      proteins important for biological processes involved in the generation of
      precursor metabolites and energy through the breakdown of carbohydrates, lipids,
      and proteins. These results are significant because we identified age-associated
      proteomic changes suggestive of altered mitochondrial catabolic reactions during
      brain aging. The proteomic data described here can be found in the PRIDE Archive
      using the reference number PXD001370. A more comprehensive analysis of this data
      may be obtained from the article "Proteomic analysis and functional
      characterization of mouse brain mitochondria during aging reveal alterations in
      energy metabolism" in PROTEOMICS. 

PMID- 26217776
TI  - Mass spectrometry analysis of K63-ubiquitinated targets in response to oxidative
      stress.
AB  - The data described here provide the first large-scale analysis of lysine 63 (K63)
      linked polyubiquitin targets. Protein ubiquitination is a prominent post
      translational modification, and a variety of ubiquitin chains exists, serving a
      multitude of functions [1]. The chains differ by the lysine residue by which the
      ubiquitin monomers are linked. We used yeast Saccharomyces cerevisiae subjected
      to oxidative stress as a model to study K63 ubiquitination. K63 ubiquitinated
      targets were pulled-down by the K63-TUBE system (Tandem Ubiquitin Binding
      Entities) and analyzed by SILAC-based mass spectrometry [2]. The data are
      associated to the research article 'K63 polyubiquitination is a new modulator of
      the oxidative stress response' [3]. The mass spectrometry and the analysis
      dataset have been deposited to the ProteomeXchange Consortium
      (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository
      with the dataset identifier PXD000960. 

PMID- 26217777
TI  - Data supporting the role of the non-glycosylated isoform of MIC26 in determining
      cristae morphology.
AB  - Membrane architecture is crucially important for mitochondrial function and
      integrity. The MICOS complex is located at crista junctions and determines
      cristae membrane morphology and the formation of crista junctions. Here we
      provide data of the bona fide MICOS subunit MIC26 for determining cristae
      morphology. MiRNA-mediated downregulation of MIC26 results in higher protein
      levels of MIC27 and in lower levels of Mic10. Using a miRNA-resistant form to
      MIC26 we show that this effect is specific to MIC26. Our data further demonstrate
      that depletion of MIC26 primarily affects the level of the 22 kDa mitochondrial
      isoform of MIC26 but not the amount of the secreted 55 kDa isoform of MIC26.
      Depletion of MIC27, however, increases secretion of the latter isoform.
      Overexpression of a myc-tagged version of MIC26 resulted in altered cristae
      morphology with swollen and partly vesicular cristae-structures. 

PMID- 26217778
TI  - A 2-D guinea pig lung proteome map.
AB  - Guinea pigs represent an important model for a number of infectious and non
      infectious pulmonary diseases. The guinea pig genome has recently been sequenced
      to full coverage, opening up new research avenues using genomics, transcriptomics
      and proteomics techniques in this species. In order to further annotate the
      guinea pig genome and to facilitate future pulmonary proteomics in this species
      we constructed a 2-D guinea pig proteome map including 486 protein
      identifications and post translational modifications (PTMs). The map has been up
      loaded to the UCD 2D-PAGE open access database (http://proteomics
      portal.ucd.ie/). Transit peptides, N-terminal acetylations and other PTMs are
      available via Peptideatlas (ftp://PASS00619:NM455hi@ftp.peptideatlas.org/). This
      dataset is associated with a research article published in the Journal of
      Proteomics [1]. 

PMID- 26217779
TI  - The capture proteasome assay (CAPA) to evaluate subtype-specific proteasome
      inhibitors.
AB  - We recently developed a new assay to measure proteasome activity in vitro (CAPA
      for capture proteasome assay) [1], based on proteasome capture on an antibody
      coated plate. When used with lysates originating from cells expressing either
      standard proteasome, immunoproteasome or intermediate proteasomes beta5i or
      beta1i-beta5i, this assay allows the individual monitoring of the chymotrypsin
      like, trypsin-like and caspase-like activities of the corresponding proteasome
      subtypes. The efficiency and specificity of four proteasome inhibitors were
      studied using the CAPA assay, demonstrating the potential of this assay for the
      development of subtype-specific proteasome inhibitors. 

PMID- 26217780
TI  - Differential proteomes of the cyanobacterium Cyanothece sp. CCY 0110 upon
      exposure to heavy metals.
AB  - The proteomes of the highly efficient extracellular polymeric substances (EPS)
      producer cyanobacterium Cyanothece sp. CCY 0110, grown in medium supplemented
      with an essential metal (Cu(2+)) or a non-essential metal (Cd(2+)),were compared
      using iTRAQ technology. The data were obtained within a larger study that
      evaluated the overall effects of different heavy metals on growth/survival, EPS
      production and ultrastructure of this cyanobacterium [1]. To allow a broader
      understanding of the strategies triggered to coupe with toxic effects of the
      metals, Cyanothece's proteomes were evaluated after chronic and acute exposure to
      Cu(2+) and Cd(2+) in two independent 8-plex iTRAQ studies. For the chronic
      exposure 0.1 mg/l of Cu(2+) or 5 mg/l of Cd(2+) were used for 10 and 20 days,
      while in the acute experiments the cells were exposed to 10* these concentrations
      for 24 h. 202 and 268 proteins were identified and quantified for studies 1
      (Cu(2+)) and 2 (Cd(2+)), respectively. The majority of the proteins with
      significant fold changes were associated with photosynthesis, CO2 fixation and
      carbohydrate metabolism, translation, and nitrogen and amino acid metabolism. 

PMID- 26217781
TI  - Data in support of fumosorinone, a novel PTP1B inhibitor, activates insulin
      signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in
      diabetic KKAy mice.
AB  - This data article contains data related to the research article entitled
      "Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin
      resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice" in
      the Toxicology and Applied Pharmacology [1]. Fumosorinone (FU) is a new inhibitor
      of protein phosphatase 1B inhibitor, which was isolated from insect pathogenic
      fungi Isaria fumosorosea. FU was found to inhibit PTP1B activity in our previous
      study [2]. PTP1B is the physiological antagonist of the insulin signalling
      pathway. Inhibition of PTP 1B may increase insulin sensitivity [3]. PTP1B has
      been considered promising as an insulin-sensitive drug target for the prevention
      and the treatment of insulin-based diseases [4]. We determined the effect of FU
      on the glucose consumption of IR HepG2 cells. FU caused significant enhancement
      in glucose consumption by insulin-resistant HepG2 cells compared with control
      cells. 

PMID- 26217782
TI  - Hourly test reference weather data in the changing climate of Finland for
      building energy simulations.
AB  - Dynamic building energy simulations need hourly weather data as input. The same
      high temporal resolution is required for assessments of future heating and
      cooling energy demand. The data presented in this article concern current typical
      values and estimated future changes in outdoor air temperature, wind speed,
      relative humidity and global, diffuse and normal solar radiation components.
      Simulated annual and seasonal delivered energy consumptions for heating of
      spaces, heating of ventilation supply air and cooling of spaces in the current
      and future climatic conditions are also presented for an example house, with
      district heating and a mechanical space cooling system. We provide details on how
      the synthetic future weather files were created and utilised as input data for
      dynamic building energy simulations by the IDA Indoor Climate and Energy program
      and also for calculations of heating and cooling degree-day sums. The information
      supplied here is related to the research article titled "Energy demand for the
      heating and cooling of residential houses in Finland in a changing climate" [1]. 

PMID- 26217783
TI  - Occurrence of viral pathogens in Penaeus monodon post-larvae from aquaculture
      hatcheries.
AB  - Viral pathogens appear to exert the most significant constraints on the growth
      and survival of crustaceans under culture conditions. The prevalence of viral
      pathogens White Spot Syndrome Virus (WSSV), Hepatopancreatic Parvo Virus (HPV),
      Monodon Baculo Virus (MBV) and Infectious Hypodermal and Hematopoietic Necrosis
      Virus (IHHNV) in Penaeus monodon post-larvae was studied. Samples collected from
      different hatcheries and also samples submitted by farmers from Kerala were
      analyzed. Out of 104 samples collected, WSSV was detected in 12.5% of the post
      larvae samples. Prevalence of concurrent infections by HPV, MBV and WSSV (either
      dual or triple infection) was present in 60.6% of the total post-larvae tested.
      Out of the 51 double positives, 98% showed either HPV or IHHNV infection. HPV or
      IHHNV was detected in 11 post-larval samples showing triple viral infection. This
      is the first report of IHHNV from India. Result of this study reveals the lack of
      efficient screening strategies to eradicate viruses in hatchery reared post
      larvae. 

PMID- 26217784
TI  - Data for proteomic analysis of Human monocyte-derived macrophages.
AB  - This data article is referred to the research article entitled Human monocyte
      derived macrophages are heterogeneous: proteomic profile of different phenotypes
      by Eligini et al. Eligini S., Brioschi M., Fiorelli S., Tremoli E., Banfi C.,
      Colli S. Human monocyte-derived macrophages are heterogeneous: proteomic profile
      of different phenotypes. J. Proteomics 124, 2015, 112-123. Macrophages obtained
      in vitro from blood monocytes are largely used as surrogate model of tissue
      macrophages that are heterogeneous and not easy to obtain and handle. Under
      spontaneous differentiation in vitro, monocyte-derived macrophages (MDMs) display
      two dominant subsets (round and spindle) that show different transcriptional,
      antigenic, and functional profiles mimicking, at least in part, the heterogeneity
      of tissue macrophages. This article reports the nano-LC-MS(E) analysis of the
      proteome of round and spindle MDMs allowing a deeper comprehension of macrophage
      heterogeneity. 

PMID- 26217785
TI  - Datasets from label-free quantitative proteomic analysis of human glomeruli with
      sclerotic lesions.
AB  - Human glomeruli with intermediate (i-GS) and advanced (GS) sclerotic lesions as
      well as the normal control (Nor) were captured from laser microdissection,
      digested by trypsin and subjected to shotgun LC-MS/MS analysis (LTQ-Orbitrap XL).
      The label-free quantification was performed using the Normalized Spectral Index
      (SI N ) to assess the relative molar concentration of each protein identified in
      a sample. All the experimental data are shown in this article. The data is
      associated to the research article submitted to Journal of Proteomics [1]. 

PMID- 26217786
TI  - Gene expression profiles of wild-type and isoniazid-resistant strains of
      Mycobacterium smegmatis.
AB  - The global variations in the gene expression pattern of drug treated (1/2X) and
      laboratory evolved drug-resistant strains (2XR and 4XR) of Mycobacterium
      smegmatis were obtained and compared with the M. smegmatis mc(2) 155 (WT) strain.
      The genes exhibiting two-fold change and p-value <0.05 under the treated
      conditions have been considered as differentially expressed genes (DEGs).
      Overall, the numbers of DEGs observed are 1529 in 1/2X (596-up, 933-down), 1381
      (899-up, 482-down) in 2XR and 716 in 4XR (267-up, 449-down) conditions. The data
      is publicly available through the GEO database with accession number GSE64132. 

PMID- 26217787
TI  - Crystallographic information of intermediate phases in binary Mg-X (X=Sn, Y, Sc,
      Ag) alloys.
AB  - The compositions and structures of thermodynamically stable or metastable
      precipitations in binary Mg-X (X=Sn, Y, Sc, Ag) alloys are predicted using ab
      initio evolutionary algorithm. The geometry optimizations of the predicted
      intermetallic compounds are carried out in the framework of density functional
      theory (DFT) [1]. A complete list of the optimized crystallographic information
      (in cif format) of the predicted intermetallic phases is presented here. The data
      is related to "Predictions on the compositions, structures, and mechanical
      properties of intermediate phases in binary Mg-X (X=Sn, Y, Sc, Ag ) alloys" by
      Liu et al. [2]. 

PMID- 26217788
TI  - Data on electrical properties of nickel modified potassium polytitanates
      compacted powders.
AB  - Potassium polytitanates are new promising type of ferroelectric ceramic materials
      with high ionic conductivity, highly polarizable structure and extremely high
      permittivity. Its structure is formed by [TiO6] octahedral units to layers with
      mobile potassium and hydroxonium ions in-between. The treatment in solutions
      containing nickel ions allows forming heterostructured materials which consist of
      potassium polytitanate particles intercalated by Ni(2+) ions and/or decorated by
      nickel oxides NiO x . This modification route is fully dependant on solution pH,
      i.e. in acidic solutions the intercalation process prevails, in alkaline
      solutions potassium polytitanate is mostly decorated by the oxides. Therefore,
      electronic structure and electrical properties can be regulated depending on
      modification conditions, pH and ions concentration. Here we report the data on
      electric properties of potassium titanate modified in nickel sulfate solutions at
      different pH. 

PMID- 26217789
TI  - Transcriptomic changes in mouse embryonic stem cells exposed to thalidomide
      during spontaneous differentiation.
AB  - Thalidomide is a potent developmental toxicant that induces a range of birth
      defects, notably severe limb malformations. To unravel the molecular mechanisms
      underpinning the teratogenic effects of thalidomide, we used microarrays to study
      transcriptomic changes induced by thalidomide in an in vitro model based on the
      differentiation of mouse embryonic stem cells (mESCs), and published the major
      findings in a research article entitled "Thalidomide induced early gene
      expression perturbations indicative of human embryopathy in mouse embryonic stem
      cells" [1]. The data presented herein contains complementary information related
      to the aforementioned research article. 

PMID- 26217790
TI  - Sequencing data and MLPA analysis data in support of the effectiveness and
      reliability of an asymmetric PCR-Based approach in preparing long MLPA probes.
AB  - ABI PRISM 3100 Genetic Analyzer, a multi-color fluorescence-based DNA analysis
      system with 16 capillaries operating in parallel, was ideal tool both for DNA
      sequencing and DNA fragment analysis [1,2]. To demonstrate the effectiveness and
      reliability of an asymmetric PCR-Based approach (X.Y. Ling, G.M. Zhang, G. Pan,
      H. Long, Y.H. Cheng, C.Y. Xiang, L. Kang, F. Chen, Z.N. Chen, Preparing long
      probes by an asymmetric PCR-based approach for multiplex ligation-dependent probe
      amplification (MLPA), Anal. Biochem. (2015),
      http://dx.doi.org/10.1016/j.ab.2015.03.031, in press) in preparing the long MLPA
      probes that were generated with a M13-based method before [4], some prepared long
      MLPA probes were sequenced and then tested in MLPA analysis. Sequencing data
      shows that the long MLPA probes were identical to the designed ones, indicating
      the long probes can be easily prepared with the new method, and the MPLA analysis
      data shows that the results of MPLA analysis with these long probes were as same
      accurate and specific as with ones prepared with other methods. The sequencing
      data was not presented in the research article (X.Y. Ling, G.M. Zhang, G. Pan, H.
      Long, Y.H. Cheng, C.Y. Xiang, L. Kang, F. Chen, Z.N. Chen, Preparing long probes
      by an asymmetric PCR-based approach for multiplex ligation-dependent probe
      amplification (MLPA), Anal. Biochem. (2015), 10.1016/j.ab.2015.03.031, in press),
      but the MLPA analysis data was converted into figure 4 and figure 5 of the
      research article. 

PMID- 26217792
TI  - Synthesis and structural data of a Fe-base sodium metaphosphate compound,
      NaFe(PO3)3.
AB  - This data article contains the synthesis and structure information of a new Fe
      base sodium metaphosphate compound, which is related to the research article
      entitled 'Synthesis, structural, magnetic and sodium deinsertion/insertion
      properties of a sodium ferrous metaphosphate, NaFe(PO3)3' by Lin et al. [1]. The
      research article has reported a new Fe-base metaphosphate compound NaFe(PO3)3,
      which is discovered during the exploration of the new potential electrode
      materials for sodium-ion batteries. In this data article, the synthesized process
      of this metaphosphate compound and the morphology of the obtained sample will be
      provided. The high-power XRD Rietveld refinement is applied to determine the
      crystal structure of this metaphosphate compound and the refinement result
      including the main refinement parameters, atomic coordinate and some important
      lattace parameters are stored in the cif file. Also, the refined structure has be
      evaluated by checkcif report and the result is also provided as the supplementary
      materials. 

PMID- 26217791
TI  - Quantitative analysis of PPT1 interactome in human neuroblastoma cells.
AB  - Mutations in the CLN1 gene that encodes Palmitoyl protein thioesterase 1 (PPT1)
      or CLN1, cause Infantile NCL (INCL, MIM#256730). PPT1 removes long fatty acid
      chains such as palmitate from modified cysteine residues of proteins. The data
      shown here result from isolated protein complexes from PPT1-expressing SH-SY5Y
      stable cells that were subjected to single step affinity purification coupled to
      mass spectrometry (AP-MS). Prior to the MS analysis, we utilised a modified
      filter-aided sample preparation (FASP) protocol. Based on label free quantitative
      analysis of the data by SAINT, 23 PPT1 interacting partners (IP) were identified.
      A dense connectivity in PPT1 network was further revealed by functional coupling
      and extended network analyses, linking it to mitochondrial ATP synthesis coupled
      protein transport and thioester biosynthetic process. Moreover, the terms:
      inhibition of organismal death, movement disorders and concentration of lipid
      were predicted to be altered in the PPT1 network. Data presented here are related
      to Scifo et al. (J. Proteomics, 123 (2015) 42-53). 

PMID- 26217793
TI  - Data of cost-optimality and technical solutions for high energy performance
      buildings in warm climate.
AB  - The data reported in this article refers to input and output information related
      to the research articles entitled Assessment of cost-optimality and technical
      solutions in high performance multi-residential buildings in the Mediterranean
      area by Zaca et al. (Assessment of cost-optimality and technical solutions in
      high performance multi-residential buildings in the Mediterranean area, in
      press.) and related to the research article Cost-optimal analysis and technical
      comparison between standard and high efficient mono residential buildings in a
      warm climate by Baglivo et al. (Energy, 2015, 10.1016/j.energy.2015.02.062, in
      press). 

PMID- 26217794
TI  - Integrated analysis of mRNA and miRNA expression in response to interleukin-6 in
      hepatocytes.
AB  - Understanding the interactions between miRNAs and genes they regulate during the
      acute phase response is crucial to our understanding of inflammatory diseases and
      processes. Inducing the acute phase response in hepatocytes by stimulating them
      with interleukin-6 [1] and then examining global changes in mRNA and miRNA
      expression can provide insight into the timing and dynamics of these
      interactions. Here we provide additional data for our study, Ref. [2]. In this
      data, we identify and validate IL-6-induced changes in gene expression [3-6] and
      their functional relationships over time and between cell types by gene ontology
      [7,8]. We also provide data showing the enrichment of miRNA binding motifs in the
      3'UTRs of differentially expressed genes [9], and their predicted gene targets
      derived from our RNA-seq data [10]. 

PMID- 26217795
TI  - Datasets from an interaction proteomics screen for substrates of the
      SCF(betaTrCP) ubiquitin ligase.
AB  - An affinity purification-mass spectrometry (AP-MS) method was employed to
      identify novel substrates of the SCF(betaTrCP) ubiquitin ligase. A FLAG-HA tagged
      version of the F-box protein betaTrCP2, the substrate recognition subunit of
      SCF(betaTrCP), was used as bait. betaTrCP2 wild type and the two mutants
      betaTrCP2-R447A and betaTrCP2-DeltaF were expressed and purified from HEK293T
      cells to be able to discriminate between potential substrates of SCF(betaTrCP)
      and unspecific binders. Affinity-purified samples were analyzed by mass
      spectrometry-based proteomics, applying ultra-high performance liquid
      chromatography (UHPLC) coupled to high-resolution tandem mass spectrometry. The
      raw mass spectrometry data have been deposited to the PRIDE partner repository
      with the identifiers PXD001088 and PXD001224. The present dataset is associated
      with a research resource published in T.Y. Low, M. Peng, R. Magliozzi, S.
      Mohammed, D. Guardavaccaro, A.J.R. Heck, A systems-wide screen identifies
      substrates of the SCF(betaTrCP) ubiquitin ligase. Sci. Signal. 7 (2014) rs8-rs8,
      10.1126/scisignal.2005882. 

PMID- 26217796
TI  - Data supporting the identification of compound for inhibition of survivin of
      colorectal cancer by using ingenuity pathway analysis of gene expression
      profiling of colorectal cancer tissues.
AB  - The data in this article is related to the research article entitled, "Targeting
      of Multiple Oncogenic Signaling Pathways by Hsp90 Inhibitor Alone or in
      Combination with Berberine for Treatment of Colorectal Cancer" [1].
      Overexpression of survivin induces resistance to various anticancer therapies
      such as chemotherapy and radiation therapy in colorectal cancer (CRC) cells. To
      determine significant correlations of biological functions/pathways with
      survivin, 4567 significant genes were analyzed from the GEO DataSet (GSE21815) of
      CRC and these were overlaid onto a global molecular network developed from
      information contained in the Ingenuity Pathway Analysis (IPA) database. The data
      here present the most significant disease and disordered biological functions,
      significant molecular/cellular functions and significant categories in
      physiological development/system functions which were associated with CRC. The
      top 10 canonical signaling pathways associated with CRC were categorize in order
      based on the level of statistical significance. 

PMID- 26217797
TI  - Prenatal alcohol exposure alters gene expression in the rat brain: Experimental
      design and bioinformatic analysis of microarray data.
AB  - We previously identified gene expression changes in the prefrontal cortex and
      hippocampus of rats prenatally exposed to alcohol under both steady-state and
      challenge conditions (Lussier et al., 2015, Alcohol.: Clin. Exp. Res., 39, 251
      261). In this study, adult female rats from three prenatal treatment groups (ad
      libitum-fed control, pair-fed, and ethanol-fed) were injected with physiological
      saline solution or complete Freund's adjuvant (CFA) to induce arthritis (adjuvant
      induced arthritis, AA). The prefrontal cortex and hippocampus were collected 16
      days (peak of arthritis) or 39 days (during recovery) following injection, and
      whole genome gene expression was assayed using Illumina's RatRef-12 expression
      microarray. Here, we provide additional metadata, detailed explanations of data
      pre-processing steps and quality control, as well as a basic framework for the
      bioinformatic analyses performed. The datasets from this study are publicly
      available on the GEO repository (accession number GSE63561). 

PMID- 26217798
TI  - Expanding a tyrosyl-tRNA synthetase assay to other aminoacyl-tRNA synthetases.
AB  - Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their
      cognate tRNAs. In general, aminoacyl-tRNA synthetase assays require
      stoichiometric amounts of tRNA, which limits their sensitivity while increasing
      their cost. This requirement for stoichiometric amounts of tRNA can be alleviated
      if the aminoacyl-tRNA product is cleaved following the tRNA aminoacylation
      reaction, regenerating the free tRNA substrate. This data article is related to
      the research article entitled "A continuous tyrosyl-tRNA synthetase assay that
      regenerates the tRNA substrate" in which this approach is used to develop a
      continuous spectrophotometric assay for tyrosyl-tRNA synthetase [1]. Here we
      present enzymes that can be used to cleave the aminoacyl-tRNA product for at
      least 16 of the 20 naturally occurring amino acids. These enzymes can be used to
      extend the tyrosyl-tRNA synthetase assay to other aminoacyl-tRNA synthetases. 

PMID- 26217799
TI  - A concise methodology for the estimation of elemental concentration effects on
      mesoscale cohesion of non-ferrous covalent glasses: The case of Se(80-x)Ge(20
      x)In x=0,5,10,15.
AB  - The link between the electronic state and the mesoscale of covalent glasses is
      not settled. A functional means of addressing the mesoscale is via generalizing
      glass properties (e.g. such as cohesion) on the basis of atomic clusters.
      Derivation of the most representative such cluster formations is not streamlined,
      however. Here, numerical pair correlation and ab initio energetic datasets are
      presented for the case of amorphous Selenium-rich covalent glasses, which were
      obtained via a new, concise methodology, relating mesoscopic cohesion to local
      atomic order and to the system's electronic structure. The methodology consisted
      of selecting clusters on the basis of the variation of atomic environment
      statistics of total coordination, partial coordination by the matrix element and
      cluster number density along the radial direction of a Reverse Monte Carlo
      supercell, the latter attained by fitting total scattering data. 

PMID- 26217800
TI  - Metagenomic data of fungal internal transcribed Spacer and 18S rRNA gene
      sequences from Lonar lake sediment, India.
AB  - The data in this article contains the sequences of fungal Internal Transcribed
      Spacer (ITS) and 18S rRNA gene from a metagenome of Lonar soda lake, India.
      Sequences were amplified using fungal specific primers, which amplified the
      amplicon lined between the 18S and 28S rRNA genes. Data were obtained using
      Fungal tag-encoded FLX amplicon pyrosequencing (fTEFAP) technique and used to
      analyze fungal profile by the culture-independent method. Primary analysis using
      PlutoF 454 pipeline suggests the Lonar lake mycobiome contained the 29 different
      fungal species. The raw sequencing data used to perform this analysis along with
      FASTQ file are located in the NCBI Sequence Read Archive (SRA) under accession
      No. SRX889598 (http://www.ncbi.nlm.nih.gov/sra/SRX889598). 

PMID- 26217801
TI  - Data in support of large scale comparative codon usage analysis in Leishmania and
      Trypanosomatids.
AB  - This data article contains data related to the article "Comparison of codon usage
      bias across Leishmania and Trypanosomatids to understand mRNA secondary
      structure, relative protein abundance and pathway functions" by Subramanian and
      Sarkar, Genomics, 2015 (10.1016/j.ygeno.2015.05.009). The data comprises of
      sequence-based measures that quantify the effect of codon usage across genomes.
      The data thus generated represents computed values of codon usage indices like
      relative synonymous codon usage (RSCU), effective number of codons (ENC), and
      codon adaptation index (CAI), a set of single copy orthologous genes common to
      the 13 Trypanosomatids, and comparisons of CAI between genes of different
      functions. This forms a basis of comparison to infer the causes and consequences
      of codon usage bias in Leishmania and other Trypanosomatids. 

PMID- 26217802
TI  - Carbohydrate mediated drug delivery: Synthesis and characterization of new lipid
      conjugates.
AB  - A new synthetic methodology for cationic glycolipids using p-aminophenyl-alpha-d
      mannopyranoside (PAPM), p-aminophenyl-alpha-d-galactopyranoside (PAPG) was
      developed. PAPM-lipids and PAPG-lipids conjugates were also synthesized for
      targeting drugs to receptors. A binding inhibition study of synthesized p
      (dimethylamino butylamido) phenyl-alpha-d-mannopyranoside (1a) with Concanavalin
      A was performed using invertase enzyme. In addition, transfection of pSV-beta-gal
      reporter gene with was investigated in A549 cells. 

PMID- 26217803
TI  - Data supporting the physico-chemical characterization, cellular uptake and
      cytotoxicity of lipid nanocapsules.
AB  - The aim of this data article is to provide data for a basic knowledge of the
      properties of lipid nanocapsules, a new colloidal system with very promising
      applications in drug delivery. Firstly, we pay attention on how it is possible to
      determine their surface composition by means of electrokinetics measurements. On
      the other hand, we provide experimental evidences for a better understanding of
      the factors that determine the interactions of these nanoparticles with cells as
      a necessary step to guide the design of the most effective formulations.
      Additionally, we supply information about encapsulation efficiency of docetaxel,
      a potent chemotherapy drug, inside nanocapsules supporting the experimental
      cytotoxicity results of these nanosystems. 

PMID- 26217804
TI  - Prediction of the curing time to achieve maturity of the nano-cement based
      concrete using the Weibull distribution model: A complementary data set.
AB  - This data article provides a comparison data for nano-cement based concrete (NCC)
      and ordinary Portland cement based concrete (OPCC). Concrete samples (OPCC) were
      fabricated using ten different mix design and their characterization data is
      provided here. Optimization of curing time using the Weibull distribution model
      was done by analyzing the rate of change of compressive strength of the OPCC.
      Initially, the compressive strength of the OPCC samples was measured after
      completion of four desired curing times. Thereafter, the required curing time to
      achieve a particular rate of change of the compressive strength has been
      predicted utilizing the equation derived from the variation of the rate of change
      of compressive strength with the curing time, prior to the optimization of the
      curing time (at the 99.99% confidence level) using the Weibull distribution
      model. This data article complements the research article entitled "Prediction of
      the curing time to achieve maturity of the nano-cement based concrete using the
      Weibull distribution model" [1]. 

PMID- 26217805
TI  - Data set of the protein expression profiles of Luminal A, Claudin-low and
      overexpressing HER2(+) breast cancer cell lines by iTRAQ labelling and tandem
      mass spectrometry.
AB  - Breast cancer is the most common and the leading cause of mortality in women
      worldwide. There is a dire necessity of the identification of novel molecules
      useful in diagnosis and prognosis. In this work we determined the differentially
      expression profiles of four breast cancer cell lines compared to a control cell
      line. We identified 1020 polypeptides labelled with iTRAQ with more than 95% in
      confidence. We analysed the common proteins in all breast cancer cell lines
      through IPA software (IPA core and Biomarkers). In addition, we selected the
      specific overexpressed and subexpressed proteins of the different molecular
      classes of breast cancer cell lines, and classified them according to protein
      class and biological process. Data in this article is related to the research
      article "Determination of the protein expression profiles of breast cancer cell
      lines by Quantitative Proteomics using iTRAQ Labelling and Tandem Mass
      Spectrometry" (Calderon-Gonzalez et al. [1] in press). 

PMID- 26217806
TI  - Cleavable ester linked magnetic nanoparticles for labeling of solvent exposed
      primary amine groups of peptides/proteins.
AB  - Covalent labeling of solvent exposed amino acid residues using chemical
      reagents/crosslinkers followed by mass spectrometric analysis can be used to
      determine the solvent accessible amino acids of a protein. A variety of chemical
      reagents containing cleavable bonds were developed to label abundantly found
      lysine residues on the surface of protein. To achieve efficient separation of
      labeled peptides prior to mass spectrometric analysis, magnetic nanoparticles can
      be decorated with amino acid reactive functional groups and utilized for quick
      recovery of labeled peptides. [1] In this work, iron oxide magnetic nanoparticles
      (Fe3O4 MNPs) were synthesized by thermal decomposition method and coated with
      silica (SiO2@Fe3O4 MNPs) by reverse micro emulsion approach. The Fe3O4 MNPs and
      SiO2@Fe3O4 MNPs were characterized by TEM and XRD. The SiO2@Fe3O4 MNPs were
      further coated with amine groups and conjugated to N-hydroxysuccinimidyl (NHS)
      ester groups via a cleavable ester bond. Fluorescence based qualitative analysis
      of ester linked NHS ester modified SiO2@Fe3O4 MNPs was performed to confirm the
      presence of NHS ester group. The active NHS ester sites on the surface of
      SiO2@Fe3O4 MNPs were determined by depletion approach and found to be 694 active
      sites per 1 mg of SiO2@Fe3O4 MNPs. Free amine groups of a small peptide, ACTH (4
      11) were labeled by ester linked, NHS ester modified SiO2@Fe3O4 MNPs under
      physiological conditions. Superparamagnetic nature of SiO2@Fe3O4 MNPs allowed
      quick and efficient magnetic separation of labeled peptides from the solution.
      The ester bond was further cleaved to separate labeled peptides followed by mass
      spectrometric analysis. The ester linked, NHS ester modified SiO2@Fe3O4 MNPs
      introduced a mass shift of 115.09 Da on amine groups of ACTH (4-11), which was
      confirmed by mass spectrometry. 

PMID- 26217807
TI  - Global or local construction materials for post-disaster reconstruction?
      Sustainability assessment of 20 post-disaster shelter designs.
AB  - This data article presents the life cycle inventories of 20 transitional shelter
      solutions. The data was gathered from the reports 8 shelter designs [1]; 10 post
      disaster shelter designs [2]; the environmental impact of brick production
      outside of Europe [3]; and the optimization of bamboo-based post-disaster housing
      units for tropical and subtropical regions using LCA methodologies [4]. These
      reports include bill of quantities, plans, performance analysis, and lifespan of
      the studied shelters. The data from these reports was used to develop the Life
      Cycle Inventories (LCI). All the amounts were converted from their original units
      (length, volume and amount) into mass (kg) units and the transport distance into
      ton*km. These LCIs represent the production phases of each shelter and the
      transportation distances for the construction materials. Two types of distances
      were included, local (road) and international (freight ship), which were
      estimated based on the area of the country of study. Furthermore, the digital
      visualization of the shelters is presented for each of the 20 designs. Moreover,
      this data article presents a summary of the results for the categories
      Environment, Cost and Risk and the contribution to the environmental impact from
      the different building components of each shelter. These results are related to
      the article "Global or local construction materials for post-disaster
      reconstruction? Sustainability assessment of 20 post-disaster shelter
      designs"[5]. 

PMID- 26217808
TI  - Data in support of in vivo studies of silk based gold nano-composite conduits for
      functional peripheral nerve regeneration.
AB  - In the present data article we report the in vitro and in vivo biocompatibility
      of fabricated nerve conduits described in Das et al. [1]. Green synthesised gold
      nanoparticles (GNPs) were evaluated for their cytotoxicity in rat Schwann cells
      (SCTM41). We also describe herein the adhesion and proliferation of Schwann cells
      over the nanofibrous scaffolds. Methods describing surgical implantation of
      conduits in a rat sciatic nerve injury model, confirming its accurate
      implantation as well as the porosity and swelling tendency of the nerve conduits
      are illustrated in the various figures and graphs. 

PMID- 26217809
TI  - Expression profiling of long noncoding RNAs in neonatal and adult mouse testis.
AB  - In recent years, advancements in genome-wide analyses of the mammalian
      transcriptome have revealed that long noncoding RNAs (lncRNAs) is pervasively
      transcribed in the genome and an increasing number of studies have demonstrated
      lncRNAs as a new class of regulatory molecules are involved in mammalian
      development (Carninci et al. (2005); Fatica and Bozzoni (2014)), but very few
      studies have been conducted on the potential roles of lncRNAs in mammalian testis
      development. To get insights into the expression patterns of lncRNA during mouse
      testis development, we investigated the lncRNAs expression profiles of neonatal
      and adult mouse testes using microarray platform and related results have been
      published (Sun et al., PLoS One 8 (2013) e75750.). Here, we describe in detail
      the experimental system, methods and validation for the generation of the
      microarray data associated with our recent publication (Sun et al., PLoS One 8
      (2013) e75750.). Data have been deposited to the Gene Expression Omnibus (GEO)
      database repository with the dataset identifier GSE43442. 

PMID- 26217810
TI  - Lipid and protein maps defining arterial layers in atherosclerotic aorta.
AB  - Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are
      needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to
      identify ongoing molecular changes in atherosclerosis development. Mass
      Spectrometry Imaging (MSI) accounts with the unique advantage of analyzing
      proteins and metabolites (lipids) while preserving their original localization;
      thus two dimensional maps can be obtained. Main molecular alterations were
      investigated in a rabbit model in response to early development of
      atherosclerosis. Aortic arterial layers (intima and media) and calcified regions
      were investigated in detail by MALDI-MSI and proteins and lipids specifically
      defining those areas of interest were identified. These data further complement
      main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J.
      Proteomics. (In press); M. Martin-Lorenzo et al., J. Proteomics 108 (2014) 465
      468.) [1,2]. 

PMID- 26217811
TI  - Cell type specificity of tissue plasminogen activator in the mouse barrel cortex.
AB  - We provide data in this article related to (C.C. Chen et al.,. Neurosci. Lett.,
      599 (2015) 152-157.) [1] where the expression of tissue plasminogen activator
      (tPA) is expressed by the whisker representation in the somatosensory cortex.
      Here, we provide immunocytochemistry data indicating that tPA is expressed by
      putative excitatory neurons as well as parvalbumin+ interneurons but not by
      somatostatin+ inhibitory interneurons. We also provide data showing that
      microglia do not normally express high levels of tPA, but upregulate their levels
      following cortical penetration with a recording electrode. 

PMID- 26217812
TI  - Quantitative proteome changes in Arabidopsis thaliana suspension-cultured cells
      in response to plant natriuretic peptides.
AB  - Proteome changes in the Arabidopsis thaliana suspension cells in response to the
      A. thaliana plant natriuretic peptide (PNP), AtPNP-A (At2g18660) were assessed
      using quantitative proteomics employing tandem mass tag (TMT) labeling and tandem
      mass spectrometry (LC-MS/MS). In this study, we characterized temporal responses
      of suspension-cultured cells to 1 nM and 10 pM AtPNP-A at 0, 10 and 30 min post
      treatment. Both concentrations we found to yield a distinct differential proteome
      signature. The data shown in this article are associated with the article "Plant
      natriuretic peptides induce a specific set of proteins diagnostic for an adaptive
      response to abiotic stress" by Turek et al. (Front. Plant Sci. 5 (2014) 661) and
      have been deposited to the ProteomeXchange with identifier PXD001386. 

PMID- 26217813
TI  - Redox proteomic analysis of the gastrocnemius muscle from adult and old mice.
AB  - The data provides information in support of the research article, "Differential
      Cysteine Labeling and Global Label-Free Proteomics Reveals an Altered Metabolic
      State in Skeletal Muscle Aging", Journal of Proteome Research, 2014, 13 (11),
      2008-21 [1]. Raw data is available from ProteomeXchange [2] with identifier
      PDX001054. The proteome of gastrocnemius muscle from adult and old mice was
      analyzed by global label-free proteomics and the relative quantification of
      specific reduced and reversibly oxidized Cysteine (Cys) residues was performed
      using Skyline [3]. Briefly, reduced Cysteine (Cys) containing peptides was
      alkylated using N-ethylmalemide (d0-NEM). Samples were desalted and reversibly
      oxidized Cys residues were reduced using tris(2-carboxyethyl)phosphine (TCEP) and
      the newly formed reduced Cys residues were labeled with heavy NEM( d5-NEM). Label
      free analysis of the global proteome of adult (n=5) and old (n=4) gastrocnemius
      muscles was performed using Peaks7TM mass spectrometry data analysis software
      [4]. Relative quantification of Cys containing peptides that were identified as
      reduced (d(0) NEM labeled) and reversibly oxidized d(5)-NEM labeled was performed
      using the intensity of their precursor ions in Skyline. Results indicate that
      muscles from old mice show reduced redox flexibility particularly in proteins
      involved in the generation of precursor metabolites and energy metabolism,
      indicating a loss in the flexibility of the redox energy response. 

PMID- 26217814
TI  - In silico analyses of dystrophin Dp40 cellular distribution, nuclear export
      signals and structure modeling.
AB  - Dystrophin Dp40 is the shortest protein encoded by the DMD (Duchenne muscular
      dystrophy) gene. This protein is unique since it lacks the C-terminal end of
      dystrophins. In this data article, we describe the subcellular localization,
      nuclear export signals and the three-dimensional structure modeling of putative
      Dp40 proteins using bioinformatics tools. The Dp40 wild type protein was
      predicted as a cytoplasmic protein while the Dp40n4 was predicted to be nuclear.
      Changes L93P and L170P are involved in the nuclear localization of Dp40n4
      protein. A close analysis of Dp40 protein scored that amino acids
      (93)LEQEHNNLV(101) and (168)LLLHDSIQI(176) could function as NES sequences and
      the scores are lost in Dp40n4. In addition, the changes L93/170P modify the
      tertiary structure of putative Dp40 mutants. The analysis showed that changes of
      residues 93 and 170 from leucine to proline allow the nuclear localization of
      Dp40 proteins. The data described here are related to the research article
      entitled "EF-hand domains are involved in the differential cellular distribution
      of dystrophin Dp40" (J. Aragon et al. Neurosci. Lett. 600 (2015) 115-120) [1]. 

PMID- 26217815
TI  - Sampling and composition of airborne particulate matter (PM10) from two locations
      of Mexico City.
AB  - The PM10 airborne particulate matter with an aerodynamic diameter <=10 um is
      considered as a risk factor of various adverse health outcomes, including lung
      cancer. Here we described the sampling and composition of PM10 collected from an
      industrial zone (IZ), and a commercial zone (CZ) of Mexico City. The PM10 was
      collected with a high-volume sampler in the above mentioned locations and both
      types of PM10 sampled were characterized by the content of polycyclic aromatic
      hydrocarbons (PAHs), metals, and endotoxin. The endotoxin PM10 content from IZ
      and CZ displayed 138.4 UE/mg and 170.4 UE/mg of PM10, respectively. 

PMID- 26217816
TI  - Construction of Brassica A and C genome-based ordered pan-transcriptomes for use
      in rapeseed genomic research.
AB  - This data article reports the establishment of the first pan-transcriptome
      resources for the Brassica A and C genomes. These were developed using existing
      coding DNA sequence (CDS) gene models from the now-published Brassica oleracea
      TO1000 and Brassica napus Darmor-bzh genome sequence assemblies representing the
      chromosomes of these species, along with preliminary CDS models from an updated
      Brassica rapa Chiifu genome sequence assembly. The B. rapa genome sequence
      scaffolds required splitting and re-ordering to match the expected genome
      organisation based on a high density SNP linkage map, but the B. oleracea
      assembly was used unchanged. The resulting B. rapa (A genome) pseudomolecules
      contained 47,656 ordered CDS models and the B. oleracea (C genome)
      pseudomolecules contained 54,766 ordered CDS models. Interpolation of B. napus
      CDS models not already represented by orthologues resulted in 52,790 and 63,308
      ordered CDS models in the A and C pan-transcriptomes, an increase of 13,676
      overall. Comparison of the organisation of this resource with publicly available
      genome sequences for B. napus showed excellent consistency for the B. napus
      Darmor-bzh resource, but more breakdown of collinearity for the B. napus ZS11
      resource. CDS datasets comprising the pan-transcriptomes are available with this
      article (B. rapa) or from public repositories (B. oleracea and B. napus). 

PMID- 26217817
TI  - Forest baseline and deforestation map of the Dominican Republic through the
      analysis of time series of MODIS data.
AB  - Deforestation is one of the major threats to habitats in the Dominican Republic.
      In this work we present a forest baseline for the year 2000 and a deforestation
      map for the year 2011. Maps were derived from Moderate Resolution Imaging
      Radiometer (MODIS) products at 250 m resolution. The vegetation continuous fields
      product (MOD44B) for the year 2000 was used to produce the forest baseline, while
      the vegetation indices product (MOD13Q1) was used to detect change between 2000
      and 2011. Major findings based on the data presented here are reported in the
      manuscript "Habitat suitability and protection status of four species of
      amphibians in the Dominican Republic" (Sangermano et al., Appl. Geogr.,) [7].63,
      2015, 55-65. 

PMID- 26217818
TI  - Quantitative analysis of the myelin g-ratio from electron microscopy images of
      the macaque corpus callosum.
AB  - We provide a detailed morphometric analysis of eight transmission electron
      micrographs (TEMs) obtained from the corpus callosum of one cynomolgus macaque.
      The raw TEM images are included in the article, along with the distributions of
      the axon caliber and the myelin g-ratio in each image. The distributions are
      analyzed to determine the relationship between axon caliber and g-ratio, and
      compared against the aggregate metrics (myelin volume fraction, fiber volume
      fraction, and the aggregate g-ratio), as defined in the accompanying research
      article entitled 'In vivo histology of the myelin g-ratio with magnetic resonance
      imaging' (Stikov et al., NeuroImage, 2015). 

PMID- 26217819
TI  - Data from human salivary proteome - A resource of potential biomarkers for oral
      cancer.
AB  - Salivary proteins are an important source for developing marker-based assays for
      oral cancers. To get an insight into the proteins present in human saliva, we
      applied multiple strategies involving affinity-based depletion of abundant
      proteins, fractionation of the resulting proteins or their tryptic peptides
      followed by LC-MS/MS analysis, using high resolution mass spectrometry. By
      integrating the protein identifications observed by us with those from similar
      workflows employed in earlier investigations, we compiled an updated salivary
      proteome. We have mapped the salivary proteome to the published data on
      differentially expressed proteins from oral cancer tissues and also for their
      secretory features using prediction tools, SignalP 4.1, TMHMM 2c and Exocarta.
      Proteotypic peptides for the subset of proteins implicated in oral cancer and
      mapped to any two of the prediction tools for secretory potential have been
      listed. The data here are related to the research article "Human saliva proteome 
      a resource of potential biomarkers for oral cancer" in the Journal of Proteomics
      [1]. 

PMID- 26217820
TI  - Myristoylation profiling in human cells and zebrafish.
AB  - Human cells (HEK 293, HeLa, MCF-7) and zebrafish embryos were metabolically
      tagged with an alkynyl myristic acid probe, lysed with an SDS buffer and tagged
      proteomes ligated to multifunctional capture reagents via copper-catalyzed alkyne
      azide cycloaddition (CuAAC). This allowed for affinity enrichment and high
      confidence identification, by delivering direct MS/MS evidence for the
      modification site, of 87 and 61 co-translationally myristoylated proteins in
      human cells and zebrafish, respectively. The data have been deposited to
      ProteomeXchange Consortium (Vizcaino et al., 2014 Nat. Biotechnol., 32, 223-6)
      (PXD001863 and PXD001876) and are described in detail in Multifunctional reagents
      for quantitative proteome-wide analysis of protein modification in human cells
      and dynamic protein lipidation during vertebrate development' by Broncel et al.,
      Angew. Chem. Int. Ed. 

PMID- 26217821
TI  - Data supporting the design and evaluation of a universal primer pair for
      pseudogene-free amplification of HPRT1 in real-time PCR.
AB  - Hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) is a common housekeeping
      gene for sample normalization in the quantitative reverse transcriptase
      polymerase chain (qRT-PCR). However, co-amplification of HPRT1 pseudogenes may
      affect accurate results obtained in qRT-PCR. We designed a primer pair (HPSF) for
      pseudogene-free amplification of HPRT1 in qRT-PCR [1]. We showed specific
      amplification of HPRT1 mRNA in some common laboratory cell lines, including HeLa,
      NIH/3T3, CHO, BHK, COS-7 and VERO. This article provides data supporting the
      presence and location of HPRT1 pseudogenes within human and mouse genome, and the
      strategies used for designing primers that avoid the co-amplification of
      contaminating pseudogenes in qRT-PCR. In silico analysis of human genome showed
      three homologous sequences for HPRT1 on chromosomes 4, 5 and 11. The mRNA
      sequence of HPRT1 was aligned with the pseudogenes, and the primers were designed
      toward 5' end of HPRT1 mRNA that was only specific to HPRT1 mRNA not to the
      pseudogenes. The standard curve plot generated by HPSF primers showed the
      correlation coefficient of 0.999 and the reaction efficiency of 99.5%. Our
      findings suggest that HPSF primers can be recommended as a candidate primer pair
      for accurate and reproducible qRT-PCR assays. 

PMID- 26217822
TI  - Abstracts of the British Association of Urological Surgeons Annual Meeting.
      Manchester, United Kingdom. June 15-18, 2015.

PMID- 26217823
TI  - Tips and Tricks  in Intra-Detrusor  Botulinum Toxin A (BoNTA) Injections.

PMID- 26217824
TI  - Management of BPH  Larger Than 100 mL: Simple Prostatectomy  Versus Laser
      Transurethral Surgery.

PMID- 26217825
TI  - High-density genomic analysis reveals basis  of spherocytosis in myelodysplastic 
      syndrome.

PMID- 26217826
TI  - RESPONSE: Research Networks=Shared Sacrifice and Success.

PMID- 26217827
TI  - An Introduction to Wilderness Emergency Medical Services Medical Director Course.

PMID- 26217828
TI  - [Use of electronic health record systems by   office-based pediatricians].

PMID- 26217829
TI  - [Acute and late coronary outcomes in   1073 patients with Kawasaki disease with  
      and without intravenous gamma-inmunoglobulin  therapy].

PMID- 26217830
TI  - [Effects of vaccination on invasive   pneumococcal disease in South Africa].

PMID- 26217831
TI  - [Effect of oximetry on hospitalization in   bronchiolitis. a randomized clinical
      trial].

PMID- 26217832
TI  - A new species of Neocypholaelaps Vitzthum (Acari: Ameroseiidae), with notes on
      the cheliceral lobes and ventral pore-like structures of mites of this family.
AB  - Neocypholaelaps kreiteri n. sp. is described based on the morphology of adult
      females, males, deutonymphs, protonymphs and larvae collected on inflorescences
      of Cocos nucifera L. (Arecaceae) in La Reunion Island, Indian Ocean. This is the
      first species of Neocypholaelaps reported from that island. It is most similar to
      N. cocos Evans, 1963 and N. stridulans Evans, 1955. A discussion is presented
      about the presence of cheliceral lobes and the absence of pilus dentilis on the
      fixed cheliceral digit of ameroseiid species, relating that to what has been
      reported for the Melicharidae and the Phytoseiidae. A discussion is also
      presented about the identity of a pore-like structure positioned anteriad of the
      genital lyrifissures (iv5) in many ameroseiids. These are interpreted as being a
      pore that in many ameroseiids and in other Gamasina are often indistinctly and
      located close to the posteromesad margin of coxae IV, on the posterior end of the
      exopodal shield.

PMID- 26217833
TI  - Cavernicolous Arrhopalites abchasicus sp. nov. (Collembola: Symphypleona:
      Arrhopalitidae) from the West Caucasus with a key to the World species of the
      genus.
AB  - A new troglobiont species of Collembola, Arrhopalites abchasicus sp. nov., from
      Psyrtskha Cave in Novy Afon (West Caucasus, Abkhazia) is described. Subdivision
      of the genus Arrhopalites on diversus, caecus and harveyi groups of species is
      proposed and identification key to the World species is provided.

PMID- 26217834
TI  - A new species of the genus Pleuroxus Baird (Cladocera: Anomopoda: Chydoridae)
      from Jeju Island, South Korea.
AB  - A new species of the genus Pleuroxus Baird (Cladocera: Anomopoda: Chydoridae) is
      described from Jeju Island, South Korea. P. jejuensis sp. nov. is the closest
      relative of the aduncus-like species from southern hemisphere instead of P.
      aduncus s. str. It shares with P. wittsteini Studer, 1878 in: (1) brown colour;
      (2) absence of denticles on postero-ventral portion of valve; (3) unusually short
      postpore distance; (4) grouped postanal teeth. P. jejuensis sp. nov. differs from
      P. wittsteini in: (1) smaller postpore distance; (2) submarginal setules on inner
      side of the posterior valve margin; (3) prominent postero-dorsal angle of the
      postabdomen; (4) only two postanal teeth in each group; (5) longer proximalmost
      basal spine of the postabdominal claw; (6) very short accessory seta on limb I.
      The wittsteini-like chydorines seem to be remnants of an old, pan-continental
      species group.

PMID- 26217835
TI  - Graphopsocus (Psocoptera: Stenopsocidae) newly recorded from Vietnam, with one
      new species.
AB  - The bark lice genus Graphopsocus Kolbe is here recorded from Vietnam with G.
      vietnamicus sp. n. distinguished by dis tinctive forewing markings. A key is
      provided to adults of Graphopsocus species from Southeast Asia.

PMID- 26217836
TI  - Molecular and morphological characterization of two avian malaria parasites
      (Haemosporida: Plasmodiidae), with description of Plasmodium homonucleophilum n.
      sp.
AB  - Plasmodium hoionucleophilum n. sp. was described from the Common Grasshopper
      Warbler Locustella naevia based on the morphology of blood stages and partial
      sequences of the mitochondrial cytochrome b (cyt b) gene. This malaria parasite
      belongs to the subgenus Novyella; it can be readily distinguished from all
      described Novyella parasites due to two features, i. e. the strict adherence of
      its meronts to the nuclei of infected erythrocytes and the lack of such adherence
      in the case of gametocytes. We also found the lineage pLZFUS01 in Red-Backed
      Shrike Lanius collurio, identified this parasite and conclude that it belongs to
      Plasiodium relictum. Illustrations of blood stages of these two parasites are
      given. DNA lineages associated with P. hoionucleophilum (pSW2, GenBank KC342643)
      and P. relictum (pLZFUS01, GenBank KC342644) are reported and can be used for
      molecular identification of these malarial infections. Phylogenetic analysis
      determines DNA lineages closely related to both reported parasites and is in
      accordance with the parasites' morphological identification. This study
      contributes to barcoding of avian malaria parasites using partial sequences of
      cyt b gene.

PMID- 26217837
TI  - Contribution to the knowledge of the genus Vestalenula Rossetti & Martens, 1998
      (Crustacea, Ostracoda, Darwinulidae), with the description of a new species, V.
      carinata n. sp., from the island of Florianopolis, Brazil.
AB  - The genus Vestalenula is the most species rich in the putative ancient asexual
      ostracod Family Darwinulidae. Several new Recent species were described from
      various continents, mostly based on carapace shape and structure. These species
      were found in a variety of aquatic and (semi-) terrestrial habitats, including
      springs, streams, interstitial waters, leaf litter in forests and in splash zones
      of waterfalls. Here, we describe V carinata n. sp. from moist leaf litter,
      collected from the Brazilian island of Florian6polis. The species belongs to the
      danielopoli-lineage within the genus because of its elongated internal tooth in
      the left valve and elongated external keel on the right valve. It can be
      distinguished from all other species in this group by its size, its L/H ratio and
      the relative length of the keel. The relationship of this new species to the
      enigmatic, putative marine species Senidarwinula terraenuxforna Choe, 1988, is
      discussed. An identification key to species of the genus is provided.

PMID- 26217838
TI  - Contribution to the study of arrenuroid water mites (Acari: Hydrachnidia) from
      Turkey.
AB  - In this paper, one new water mite species of the genus Arrenurus, i.e. Arrenurus
      (s.str.) ovatipetiolatus Esen & Erman sp. nov. and some new records for the
      Turkish fauna are given. The first description of the female of Arrenurus
      (s.str.) antalyensis Gulle, Boyaci & Gulle, 2011 is given. Arrenurus (s.str.)
      kermanensis Pesic, Smit & Asadi, 2011, which is only known from type locality in
      Iran, and reported here, is new record for the Turkish fauna, is redescribed.
      Arrenurus (s.str.) kurui Erman, 1993 is considered a junior synonym of Arrenurus
      (s.str.) vavrai Thon, 1899. Krendowskia (s.str.) levantensis Smit, 1997, a
      species only known from Israel and Iran, is reported first time from Turkey.

PMID- 26217839
TI  - Pinnotheres orcutti Rathbun, 1918, a new Eastern Tropical Pacific species of
      Tumidotheres Campos, 1989 (Crustacea: Brachyura: Pinnotheridae).
AB  - The lack of a protuberance in the basal antennal article in the holotype of
      Pinnotheres orcutti Rathbun, 1918, allows its removal from Pinnotheres Bosc, 1802
      [type species, P. pisumn (Linnaeus, 1767)]. The species is instead included in
      Tumidotheres Campos, 1989, because of the presence of a thick, tumid and firm
      carapace, and its surface covered with a short, dense, and deciduous tomentum;
      the third maxilliped having a propodus larger than the carpus; and the presence
      of a subspatulate dactylus of the third maxilliped medially inserted into a notch
      on the ventral margin of the propodus. Tumidotheres orcutti new combination can
      be separated from its sole Pacific Ocean congener, T. margarita Smith, 1870, by
      its unique dentition on the inner margin of the cheliped pollex, which is armed
      with a blunt proximal lobe and a row of small teeth, the two distal teeth being
      conspicuously the largest. In contrast, the pollex dentition of T. margarita
      consists of very small teeth, all similar in size.

PMID- 26217840
TI  - Phoomyia, a new genus of Dolichopodinae from the Oriental Region (Diptera:
      Dolichopodidae).
AB  - Phoomyia Naglis & Grootaert gen. nov. is described to include two new species of
      beach-dwelling dolichopodine flies from coastal Sri Lanka and Thailand: Phoontyia
      srilankensis Naglis & Brooks sp. nov. and Phoomnyia thailandensis Naglis &
      Grootaert sp. nov. The new genus is closely related to the genera Argyrochlamys
      Lamb and Pseudargyrochlamys Grichanov, and is distinguished based on characters
      of the hind leg, and features of the male and female terminalia. Adults of
      Phoomyia are found on sandy coastal beaches often near the burrows of ghost
      crabs.

PMID- 26217841
TI  - Characterization of a monophylum Echinocletodes, its exclusion from Ancorabolinae
      (Copepoda, Harpacticoida), and displacement of E. bodini and E. walvisi to
      Cletodes, including the description of two new species.
AB  - The discovery of two new species of Harpacticoida (Crustacea, Copepoda),
      Echinocletodes voightae sp. nov. (Ancorabolidae Sars, 1909) and Cletodes
      meyerorum sp. nov. (Cletodidae T. Scott, 1905 sensu Por, 1986), permitted a
      phylogenetic re-examination of the genus Echinocletodes Lang, 1936, whose
      membership in Ancorabolidae has been increasingly queried in the past decade.
      Echinocletodes voightae was discovered in wood-falls in the Gorda Ridge
      (Northeast Pacific Ocean). It resembles the type species E. armatus T. Scott,
      1903, sharing with it seven synapomorphies. In contrast, the other two species in
      the genus, E. bodini Dinet, 1974 and E. walvisi Dinet, 1974, were originally
      collected in the deep Angola Basin (SE Atlantic), and do not exhibit any of these
      synapomorphies. In fact they correspond more closely with Cletodes meyerorum,
      which is undoubtedly Cletodes Brady, 1972, due to the presence of two apomorphies
      of that genus. Consequently, both E. bodini and E. walvisi are moved from
      Echinocletodes to Cletodes. A revision of ancorabolid apomorphies showed
      ambiguities, being absent from some Ancorabolidae but present in other non
      ancorabolid taxa (like e.g. Cletodes). Ancorabolidae were, therefore, considered
      to be a paraphyletic group that requires extensive re-evaluation, additionally
      including at least the Cletodidae and Laophontidae T. Scott, 1905. Similarly when
      comparing Echinocletodes with the two ancorabolid subfamilies, Ancorabolinae
      Sars, 1909 and Laophontodinae Lang, 1944, it was revealed that many species are
      apparently distributed chaotically over several supraspecific taxa (at least
      Ancorabolidae and Cletodidae) instead of forming monophyla.

PMID- 26217842
TI  - New fossil taxa and notes on the Mesozoic evolution of Liadytidae and Dytiscidae
      (Coleoptera).
AB  - The diagnoses of Liadytidae Ponomarenko, 1977, Liadytiscinae Prokin & Ren, 2010,
      Liadytiscus Prokin & Ren, 2010 and Mesoderus Prokin & Ren, 2010 (Dytiscidae) are
      modified, and the following new taxa are described from Mesozoic fossils:
      Liadytes aspidytoides sp. n. (Liadytidae); Mesoderini trib. n., Liadyxianus
      kirejtshuki gen. n. et sp. n., Mesoderus punctatus sp. n., Mesoderus ovatus sp.
      n., Mesodytes rhantoides gen. n. et sp. n., Palaeodytes baissiensis sp. n. and
      Cretodytes incertus sp. n. (Dytiscidae). A summarized checklist of all Mesozoic
      Liadytidae and Dytiscidae known from adults is given, and an identification key
      to the genera of Mesozoic Dytiscidae known from adults is provided for the first
      time. Palaeodytes incompletus Ponomarenko, Coram & Jarzembowski, 2005 (the suffix
      of the specific epithet is emended from the original incomnpleta) is found to
      belong not to this genus, but to another one, which remains to be described. The
      fossil larva Angaragabus jurassicus Ponomarenko, 1963 from the Lower Jurassic of
      Irkutsk Oblast, Russia, probably belonging to Liadytidae, is re-examined. If this
      larva actually belongs to Liadytidae, then its morphological characters provide
      additional confirmation of the conclusion, based on the characters of adult
      liadytids, that the family is quite separate from the recent family Aspidytidae,
      and the similarity between the adults of both families results from parallel
      processes in the evolution of the superfamily Dytiscoidea. We show that the
      principal trends of morphological changes of Liadytidae and Dytiscidae during the
      Upper Jurassic and Lower Cretaceous included a consistent increase in the area of
      the metacoxal plates at the expense of decreasing area of the lateral lobes of
      the metaventrite ("wings"), flattening and loss of the lateral border of the
      elevated median area of the metaventrite, and shortening and dilation of the
      metafemur and metatibia. These changes were probably associated with an increased
      load of swimming taken by the hindlegs, which required, among other things, the
      development of swimming muscles attached to the metacoxal plates. The development
      of the hindlegs allowed diving deeper, thus being an adaptation to the nektonic
      instead of benthic lifestyle. This is confirmed by the adaptive coloration of the
      Liadytidae and Dytiscidae found in Shar Teg (Liadytes aspidytoides sp. n.),
      Yixian (Mesoderus magnus Prokin & Ren, 2010) and Baisa (Palaeodytes baissiensis
      sp. n.), in which the dorsum was darker than underside, providing camouflage in
      the depths of the water.

PMID- 26217843
TI  - Morphological description of the fourth instar larva: Culicoides cataneii and
      Culicoides sahariensis (Diptera: Ceratopogonidae).
AB  - This study was carried out of the region of Monastir in Central Tunisia, between
      July and August 2010. Larvae were collected using a floatation technique with
      magnesium sulfate in mud samples. The fourth instar larva of Culicoides cataneii
      Clastrier, 1957 and Culicoides sahariensis Callot, Kremer, Bailly-Choumara, 1970
      are described, illustrated and drawn. Measurements of instars IV are also
      presented. This is the first record of Culicoides cataneii and Culicoides
      sahariensis (Diptera: Ceratopogonidae) to Tunisia.

PMID- 26217844
TI  - Phylogenetic relationships of the comb-footed spider subfamily Spintharinae
      (Araneae, Araneoidea, Theridiidae), with generic diagnoses and a key to the
      genera.
AB  - The monophyly of Spintharinae is supported in agreement with previous analysis of
      Theridiidae by Agnarsson and Arnedo et al. We study the relationships of the
      genera within Spintharinae. Fourteen species in the genera Chrosiothes, Episinus,
      Spintharus, Steninops, and Thwaitesia constituted the ingroup, while five species
      from the genera Euryopis and Dipoena (Hadrotarsinae), as well as Latrodectus and
      Steatoda (Latrodectinae), served as outgroup taxa. The character matrix included
      49 morphological characters. Parsimony analyses using several character weighting
      strategies supported the monophyly of Spintharinae with Stemmops as sister to a
      clade that includes the remaining ingroup taxa. Chrosiothes emerged as sister to
      Episinus + Spintharus + Thwaitesia which formed a polytomy. The equally weighted,
      successive weighted, and preferred implied weight topologies, were all logically
      consistent. A key to the genera of Spintharinae and diagnoses for each genus are
      given.

PMID- 26217845
TI  - Morphology of preimaginal stages and taxonomical relationship of Synanthedon
      spuleri (Fuchs, 1908) (Lepidoptera: Sesiidae) with closely related species in
      Central Europe.
AB  - The egg, last larval instar, and pupa of Synanthedon spuleri Fuchs are described
      and illustrated. In Central Europe there is a group of four closely related
      species including S. spuleri, S. tipuliformis Clerck, S. loranthi Kralicek, and
      S. cephiformis Ochsenheimer. Thus far S. spuleri has been classified as closely
      related to S. tipuliformis. However, the results of molecular analyses and partly
      studies of the morphology of the preimaginal stages indicate that S. spuleri is
      more closely related to S. cephiformis than to S. tipuliformis. In terms of the
      response of males to similar attractants it appears that S. spuleri is more
      closely related to S. tipuliformnis; however, further research needs to be
      conducted in this respect.

PMID- 26217846
TI  - Two new species, new synonymies, and new records of Plant bugs (Hemiptera:
      Heteroptera: Miridae) from Northwestern China.
AB  - Two new species of Miridae, Myrmecophyes bykovi sp. nov. and Scirtetellus
      medvedevae sp. nov., are described from Xinjiang province of China. Illustrations
      of the male genitalia, tarsus, and pretarsus; photographs of the dorsal habitus;
      known hosts; and distributional records are provided for each species. Two new
      synonymies are established, viz. Chlainydatus laminatus Li & Liu, 2006 =
      Chlamydatus eurotiae Kerzhner, 1962; and Chlainydatus sichuanensis Li & Liu, 2006
      = Chlamydatuspullus (Reuter, 1870). The following 13 species of Miridae are
      recorded for the first time from China: Camptotylus meyeri Frey-Gessner, 1863,
      Dicyphus testaceus Reuter, 1879, Liocoris tripustulatus (Fabricius, 1781),
      Monocris griseolus Putshkov, 1974, Myrmecophyes kiritshenkoi Horvith, 1927,
      Orthotylus melanotylus Kerzhner, 1962, Phytocoris incanus Fieber, 1864,
      Psallopsis haloxyli Putshkov, 1976, Psallopsis kallidiicola Konstantinov, 1997,
      Psallus anticus (Reuter, 1876), Scirtetellus seminitens Horvith, 1904, Tuponia
      (Chlorotuponia) loginovae Drapolyuk, 1982, and Tuponia (Chlorotuponia) cristifera
      Drapolyuk, 1982. Also, the following six species of plant bugs are new records
      for Xinjiang Province: Canptotylidea suturalis (Reuter, 1904), Chlamydatus
      eurotiae Kerzhner, 1962, Compsidolon punilun (Jakovlev, 1876), Excentricoris
      pictipes (Reuter, 1878), Glaucopteruin gobicum Kerzhner, 1984, Oncotylus
      vitticeps Reuter, 1879. Pherolepis aenescens (Reuter, 1901) is indicated for
      Xinjiang and Liaoning Provinces. Indication of Scirtetellus gudali Kiritshenko
      from Inner Mongolia (Bai et al. 2006) is considered erroneous.

PMID- 26217847
TI  - Identification, distribution, and adult phenology of the carrion beetles
      (Coleoptera: Silphidae) of Texas.
AB  - The carrion beetles (Coleoptera: Silphidae) of Texas are surveyed. Thirteen of
      the 14 species, and five of the six genera, of this ecologically and forensically
      important group of scavengers that have previously been reported from Texas are
      confirmed here based on a study of 3,732 adult specimens. The one reported, but
      unconfirmed, species, Oxelytrum discicolle, was probably based on erroneous label
      data and is excluded from the Texas fauna. Two additional species, Nicrophorus
      sayi and N. investigator are discussed as possible, but unconfirmed, components
      of the fauna. Taxonomic diagnoses, Texas distribution range maps, seasonality
      profiles, and biological notes are presented for each confirmed species. The
      confirmed Texas silphid fauna of 13 species comprises 43% of the 30 species of
      this family that are known from America north of Mexico. The highest richness (11
      species) is found in the combined Austroriparian and Texan biotic provinces of
      eastern Texas. Phenologically, three species (Necrophila americana, O. rugulosum
      and Nicrophorus tomentosus) exhibit bimodal adult temporal occurrence patterns
      with peaks in the spring and late summer or fall; four species (Oiceoptoma
      noveboracense, Necrodes surinamensis, Nicrophorus carolinus, and N. orbicollis)
      exhibit unimodal occurrence patterns with a single peak in late spring or early
      summer; one species (Oiceoptonia inaequale) exhibits a unimodal occurrence
      pattern with a single peak in early spring; and five species (Thanatophilus
      truncatus, Nicrophorus americanus, N. marginatus, N. mexicanus and N. pustulatus)
      display unimodal occurrence patterns with peaks in late summer or early fall.

PMID- 26217848
TI  - Revision of the Afrotropical Lycorininae (Ichneumonidae; Hymenoptera) with
      description of a new species from South Africa.
AB  - We revise the Afrotropical Lycorininae and describe Lycorina yui Rousse & van
      Noort sp. nov. from South Africa. An illustrated key to Lycorininae species of
      the Afrotropical region is provided. Lycorina continentalis (Benoit, 1953) is
      considered a junior synonym of Lycorinafici Seyrig, 1932, and is newly reported
      from Uganda and South Africa. Online dichotomous and interactive Lucid keys are
      available at http://www.waspweb.org.

PMID- 26217849
TI  - Neohemigaster Malloch, 1939 and Pterogenia Bigot, 1859 (Diptera: Platystomatidae)
      from eastern Eurasia, with the description of four new species.
AB  - Four new species are described: Neohemigaster angustifrons sp.n. from Vietnam,
      Neohenigaster antropovi sp.n. from the Russian Far East, Neohemigaster
      tetralineata sp.n. from Taiwan and Pterogenia tenebrica sp.n. from Taiwan. In
      addition to Neohemigaster ussurica (Korneyev, 2001), six species formerly
      assigned to Pterogenia are transferred to Neoheinigaster: Neohemigaster
      eurysterna (Hendel, 1914) comb. nov., Neoheinigaster flavopicta (Hennig, 1940)
      comb. nov., Neohemigaster minuspicta (Hennig, 1940) comb. nov., Neohemigaster
      inonticola (Frey, 1964) comb. nov., Neohenigaster ornata (Hennig, 1940) comb.
      nov., and Neoheinigaster rectivena (Enderlein, 1924) comb. nov. A preliminary
      list of diagnostic characters separating the genera Pterogenia and Neohenigaster
      is compiled. A key to species of Pterogenia and Neohentigaster, known from Far
      East Russia, Japan, China, Taiwan, Vietnam and Burma, is provided.

PMID- 26217850
TI  - Review of Michalowskiya Dworakowska (Hemiptera: Cicadellidae: Typhlocybinae:
      Dikraneurini) with description of six new species from China.
AB  - A key to known species of the subgenus Michalowskiya (Michalowskiya) Dworakowska
      is provided. Detailed morphological descriptions and illustrations of six new
      species, Michalowskiya (Michalowskiya) aurantiaca, M. (M.) biprocessa, M. (M.)
      breviprocessa, M. (M.) brownistriata, M. (M.) longiprocessa, and M. (M.) pedata
      spp. nov. from China are provided.

PMID- 26217851
TI  - New Mycomya species from the Himalayas (Diptera, Mycetophilidae): 2. Subgenera
      Calomycomya, Cymomya, Neomycomya and Pavomya subg. n.
AB  - Myconya Rondani specimens from the Himalayas, mostly Nepal and Myanmar, are
      revised. Pavoniya subg. n. is described. Altogether nine species from the
      subgenera Calomycoinya, Cymnoniya, Neoinycoinya and Pavomya subg. n. are recorded
      from the Himalayas and Indian subcontinent. The paper includes a key to the
      subgenera of Myconiya and the Himalayan species of Mycomya of the four subgenera.
      The following eight new species are described: M. aonyx, M. cuon, M.
      kainbaitiensis, M. marmota, M. paguina, M. panthera, M. ratufa and M. wah.
      Mycomyafiubriata (Meigen) is recorded from Myanmar.

PMID- 26217852
TI  - A survey of East Palaearctic Lycosidae (Araneae). 9. A review of Sibirocosa with
      a description of three new species.
AB  - The East Palaearctic genus Sibirocosa Marusik, Azarkina & Koponen, 2004 is
      surveyed and three species S. koponeni sp. n. (Maritime Province), S. nadolnyi
      sp. n. and S. trilikauskasi sp. n. (both from Khabarovsk Province) are described
      from the Russian Far East. Illustrations to all six species found in East Asia
      are provided.

PMID- 26217853
TI  - New species and record of Pselaphinae (Coleoptera: Staphylinidae) from Saudi
      Arabia.
AB  - Centrophthalnus subtilissinus sp. nov. is described and the new record of
      Ctenistes staudingeri Schaufuss from Saudi Arabia is given. Both species were
      collected in the under rock ant nest of Pheidole cf. pallidula.

PMID- 26217854
TI  - A new deep-water goatfish of the genus Upeneus (Mullidae) from Vanuatu, South
      Pacific.
AB  - A new goatfish, Upeneus vanuatu (Mullidae), is described based on five specimens
      collected off two islands of Vanuatu (South Pacific), at depths of 191-321 m, and
      compared with five closely related species: Upeneus davidaroni (Red Sea), U.
      mascareinsis (Western Indian Ocean), U. stenopsis (northern Australia,
      Philippines, 127-275 m), and the more shallow-occurring Indo-West Pacific species
      U. subvittatus (26-120 m) and U. vittatus (<l00 m). The new species can be
      distinguished from all other congeneric species by the combination of four
      characters: number of gill rakers on lower limb, caudal-peduncle depth,
      interorbital length, and interdorsal distance. Strong allometric variation in
      body form between the holotype and the four smaller paratypes was found. Based on
      the lack of lateral body stripes, a rather narrow caudal peduncle depth, and
      large eyes in adults as common characteristics for U. subvittatus and the four
      deep-water Upeneus species, the so-called "stenopsis" species group can be
      distinguished from four other species groups that were established in earlier
      studies in order to facilitate intrageneric comparisons. The ecological and
      evolutionary significance of deep-water goatfishes is briefly discussed.

PMID- 26217855
TI  - Prosthetops wolybergensis sp. nov.--a giant amongst the 'minute moss beetles',
      with new data on other members of the genus (Coleoptera, Hydraenidae).
AB  - Prosthetops wolfbergensis sp. nov. (Coleoptera, Hydraenidae) is described from
      the Western and Northern Cape regions of South Africa; the new species, at up to
      4.2 mm total length, apparently being the longest 'minute moss beetle' described
      to date. Prosthetops species are characteristic inhabitants of temporary
      rainwater pools and seepages on exposed plateau in the Cape fold mountains, and
      on rock outcrops beside streams and rivers. New collection records and ecological
      data are given for members of the genus, and the female of Prosthetops pronotus
      Perkins & Balfour-Browne, 1994 is described and illustrated for the first time.

PMID- 26217856
TI  - A new Nototriton (Caudata: Plethodontidae) from Parque Nacional Montana de
      Botaderos in northeastern Honduras.
AB  - The highlands of northeastern Honduras remain under-characterized in terms of
      biological diversity, as exemplified by the regularity of new amphibian and
      reptile taxa discoveries. Following the recent description of a new species of
      Nototriton from the Sierra de Agalta in northeastern Honduras, we report the
      discovery of a second new species of Nototriton from the nearby Parque Nacional
      Montana de Botaderos. This new taxon, Nototriton mime sp. nov., is distinguished
      from other Nototriton by its distinctive pale brown dorsal coloration in adult
      males, relatively large nares, a relatively broad head, mitochondrial sequence
      divergence, and phylogenetic relationships, and is geographically isolated from
      other populations of Nototriton.

PMID- 26217857
TI  - Molecular characterization of haemosporidian parasites (Haemosporida) in yellow
      wagtail (Motacillaflava), with description of in vitro ookinetes of Haemoproteus
      motacillae.
AB  - In studies of haemosporidian systematics and taxonomy, a combination of
      microscopic examination and molecular identification has been recommended. The
      yellow wagtail (Motacillaflava) is a frequently used species in studies of host
      parasite interactions; blood parasites of this bird have been well studied using
      microscopic examination of blood films, but data on molecular characterization of
      the parasites are scattered. Here we present the first study linking several
      haemosporidian cyt b sequences with their morphospecies parasitizing the yellow
      wagtail, combining light microscopy and nested PCR methods. The lineage hYWT1 of
      Haemoproteus motacillae was the most prevalent parasite; it was recorded in 38%
      of the birds. The latter lineage and the lineages hYWT2, hYWT3, hYWT5 and hYWT6
      form a well-supported clade on the phylogenetic tree and likely represent
      intraspecific genetic variation of H. motacillae, with genetic divergence of 0.3 
      1.5 % among these lineages. Microscopic examination of smears prepared during an
      in vitro experiment, which was designed for observation of developing ookinetes,
      showed that H. motacillae ookinetes were present 5 hours after exposure of blood
      to air at 18-20 degrees  C. Ookinetes of this parasite belong to a group of large
      Haemoproteus spp. ookinetes (19.9 um in length on average). Illustrations of the
      parasites are given. Two of reported Plasmodium lineages, pCOLLI and pYWT4 are
      phylogenetically closely related to the widespread host generalist parasites
      Plasmodium relictun (cyt b lineages pSGS 1, pGRW4 and pGRW11), but it was not
      possible to establish this morphologically. This study contributes to the
      molecular identification of avian haemosporidian parasites and provides
      information on morphology of H. motacillae ookinetes, which is additional
      information assisting the microscopic identification of this species.

PMID- 26217858
TI  - A new species from southwestern China of Clematoscenea (Psocoptera: Psocidae),
      with a key to known species.
AB  - Clematoscenea spinosus sp. n. is described and illustrated as the second species
      of this genus from China, and an English redescription of C. yunnanica Li is
      provided. Updated keys are given to the known species, together with
      distributional data.

PMID- 26217859
TI  - Zyzzyzus rubusidaeus (Cnidaria, Hydrozoa, Tubulariidae), a new species of
      anthoathecate hydroid from the coast of British Columbia, Canada.
AB  - Zyzzyzus rubusidaeus, sp. nov., is described from inshore waters near the
      northern tip of Vancouver Island, British Columbia, Canada. Specimens were
      collected on rocky bottoms amongst barnacles, sponges, and compound ascidians at
      a depth of 18 m in Weynton Passage, Broughton Strait, during March, July, and
      October 2012. Polyps tend to grow in dense aggregations, often covering several
      square centimetres. Hydroids of Z. rubusidaeus most closely resemble those of Z.
      robustus Petersen, 1990 from Greenland, but differ in having aboral tentacles
      that are scattered in a narrow band around the base of the hydranth rather than
      occurring in a single whorl, thin and transparent instead of thick and stiff
      perisarc around hydrocaulus and tubers, and gonophores that arise from simple
      pedicels instead of short, stout branches. Possible embryos were present in
      female gonophores, although structures recognizable as actinula larvae have not
      been observed. The cnidome comprises small and large stenoteles, desmonemes,
      microbasic euryteles, basitrichs, and isorhizas. Polyps are a raspberry colour in
      life, a hue that has faded but little in our formalin-preserved material.
      Discovery of this hydroid brings the number of species currently recognized in
      genus Zyzzyzus Stechow, 1921 to seven.

PMID- 26217860
TI  - Taxonomic status of Cyrtoscydmus described by C. Schaufuss from the Philippines
      (Coleoptera: Staphylinidae: Scydmaeninae).

PMID- 26217861
TI  - Systematics of the caecilian family Chikilidae (Amphibia: Gymnophiona) with the
      description of three new species of Chikila from northeast India.
AB  - A taxonomic review of the monogeneric northeast Indian caecilian family
      Chikilidae is presented based on 64 specimens. Chikila fuilleri (Alcock, 1904),
      known previously only from a single specimen collected more than 100 years ago,
      is rediagnosed and characterised based on recent collections. We describe three
      additional species new to science, Chikila alcocki sp. nov., Chikila darlong sp.
      nov., and Chikila gaiduwani sp. nov. This species-level taxonomy is consistent
      with mitochondrial DNA sequence data. A key to the species of Chikila is
      presented.

PMID- 26217862
TI  - Molecular analysis validates of some informal morphological groups of Pagurus
      (Fabricius, 1775) (Anomura: Paguridae) from South America.
AB  - The systematics of the hermit crab genus Pagurus is complex, with a long history
      of taxonomic rearrangements. This group, with worldwide distribution, encompasses
      a large number of morphologically heterogeneous species. A total of 173 currently
      recognized species have been morphologically organized into 11 informal groups,
      in attempts to establish internal stability. This arrangement and the
      relationships among species of each informal group have remained obscure and have
      never been evaluated from a molecular phylogenetic viewpoint. Attempts to resolve
      these high-level classification problems have been restricted to morphological
      studies, with no satisfactory results because of the extensive overlap of the
      characters used. We evaluated the phylogenetic position of some of these informal
      groups of species of Pagurus occurring along the Pacific and Atlantic coasts of
      South America, using partial fragments of two molecular markers (16S mtDNA and
      Histone 3 nDNA). Our results indicated a clear polyphyletic arrangement of
      Pagurus; at the same time, the internal clades fit perfectly with pre-established
      informal morphological groups from South America, which may warrant a formal
      taxonomic subdivision of the genus. Additionally, the species belonging to the
      "provenzanoi group" clearly fit within a different taxon and should be reviewed.
      Also, the presence of the genus Propagurus in the ingroup could be interpreted by
      non-exclusive hypotheses: from one point of view, the genus Propagurus is nested
      within Pagurus, and therefore Pagurus is not valid as currently composed; or
      possibly, that more than one genus should be recognized among the South American
      species presently assigned to Pagurus. This latter perspective accords with the
      proposal to restrict Pagurus to only a few species.

PMID- 26217863
TI  - A checklist of cercariae (Trematoda: Digenea) in molluscs from Brazil.
AB  - A checklist of digenetic trematodes found in molluscs from Brazil is presented
      based on 127 scientific articles published after a century of studies. To date 23
      families, 35 genera and 46 species of trematodes were identified infecting 25
      species of molluscs in the country. Another 36 species described in the
      collective-group Cercaria were found in 15 species of molluscs and have not yet
      been associated with the respective adult parasites. Larvae found in 20 species
      of molluscs and grouped into 10 cercarian types are also listed.

PMID- 26217864
TI  - Ceratricula and Flandria--two new genera of Afrotropical Hesperiidae (Hesperiinae
      (incertae sedis)) for species currently placed in the genus Ceratrichia Butler.
AB  - Two genera of Afrotropical Hesperiidae are described to receive species currently
      placed in Ceratrichia Butler, where they do not belong. Ceratricula gen. nov.
      comprises a single species spanning most of the main rainforest zone from Sierra
      Leone to Uganda and south to Zambia in three subspecies, ssp. congdoni ssp. nov.
      being new and ssp. indeterminabilis Strand raised from synonymy. Flandria gen.
      nov. consists of three rare or very rare species that are limited to eastern
      Cameroun and the western Democratic Republic of Congo, which gives this genus a
      more restricted range than any other among the African forest skippers; the three
      Flandria had previously been placed in Ceratrichia, Pardaleodes, or Andronyinus.

PMID- 26217865
TI  - A new subspecies of the subgenus Ecdyonurus Eaton, 1868 (Ephemeroptera:
      Heptageniidae) from the East of Ukraine.
AB  - Ecdyonurus dispar gratificus ssp. nov. is reported from several small streams and
      rivers within the Donetsk Ridge (East of Ukraine). The new subspecies is
      described and illustrated on larvae and reared adults of both sexes. SEM
      photographs of the egg structures are presented. Critical diagnostic characters
      distinguishing the new subspecies from other representatives of the subgenus
      Ecdyonurus Eaton, 1868 and especially from the nominal subspecies are discussed.
      The data on the biology and distribution are presented.

PMID- 26217866
TI  - Three new species of the genus Neophyllobius Berlese (Acari: Camerobiidae) from
      Southern and Southwestern Iran.
AB  - Three new species of the genus Neophyllobius Berlese, 1886 are described and
      illustrated from Iran: Neophyllobius edwardi sp. nov. and Neophyllobius seemani
      sp. nov. collected from soil under oak trees; and Neophyllobius dogani sp. nov.
      collected from soil under Astragalus bushes. A key to the species of Iran is
      provided.

PMID- 26217867
TI  - Taxonomy of 'Euconnus complex'. Part II. Revision of Archiconnus Franz,
      Parapseudoconnus Franz and Mexiconnus gen. nov. (Coleoptera, Staphylinidae,
      Scydmaeninae).
AB  - Neotropical Scydmaeninae Archiconnus Franz and Parapseudoconnus Franz (with two
      subgenera) are re-defined and details of their morphology are illustrated.
      Archiconnus mexicanus Franz is placed in a separate genus Mexiconnus gen. nov.
      (resulting in a new combination Mexiconnus mexicanus (Franz)). The current
      division of Parapseudoconnus into the nominotypical subgenus and a subgenus
      Neuraphornimus Franz is weakly supported by only minor morphological differences,
      but the subgenera are retained, pending further study. Archiconnus huallaganus
      Franz, Mexiconnus mexicanus, Parapseudoconnus (s. str.) aberrans Franz and P.
      (Neuraphomimnus) simulator Franz are redescribed, while detailed redescriptions
      of P (N.)fraudulentus Franz and P (N.) mnonticola Franz were not possible due to
      partly or entirely damaged type specimens.

PMID- 26217868
TI  - Revision of the ant genus Myrmoteras of the Indo-Chiese Peninsula (Hymenoptera:
      Formicidae: Formicinae).
AB  - The Indo-Chinese species of the genus Myrmoteras are revised. We recognise one
      species in the subgenus Myagroteras and six species in the subgenus Mynnoteras
      from Vietnam, Myanmar and Thailand. Five new species are described based on the
      worker caste: M. concolor, M. jaitrongi, M. namphuong, M. opalinumn, and M.
      tonimasai, all belonging to the subgenus Myrmnoteras.

PMID- 26217869
TI  - The genus Pseudostenophylax Martynov (Trichoptera, Limnephilidae) in Japan.
AB  - I revise the Japanese species of the genus Pseudostenophylax Martynov
      (Trichoptera, Limnephilidae), and recognize 8 species including five new species,
      P. tohokuensis, P. kuharai, P. itoae, P. tanidai and P. befui, and three
      previously described species, P tochigiensis Schmid, P ondakensis (Iwata) and P.
      dentilus (Kobayashi). Pseudostenophylax takaoensis Schmid is synonymized with P.
      ondakenis. Adults and larvae of all species are described or redescribed except
      for the larval stage of P befui sp. nov.

PMID- 26217870
TI  - Ornithodoros guaporensis (Acari, Ixodida: Argasidae), a new tick species from the
      Guapore River Basin in the Bolivian Amazon.
AB  - The soft tick Ornithodoros guaporensis n. sp. (Acari: Ixodida: Argasidae) is
      described from larvae and adults. Morphological analysis and 16S rDNA sequences
      are provided. Adults were collected from a rocky fissure inhabited by bats
      located in the Amazonian forest in north-eastern Bolivia (Beni Department) close
      to the Guapord River. Larvae were obtained from eggs laid by females collected in
      the field, and which were fed on rabbits in the laboratory. Larvae of O.
      guaporensis are morphologically closely related to Ornithodoros rioplatensis,
      Ornithodoros puertoricensis and Ornithodoros talaje. Larvae of O. guaporensis and
      O. rioplatensis can be separated from O. puertoricensis and O. talaje by the
      number of pairs of dorsal setae (20 in O. guaporensis and O. rioplatensis, 18 in
      O. puertoricensis and 17 in O. talaje). Larvae of O. guaporensis and O.
      rioplatensis can be differentiated by the medial dental formula (2/2 in O.
      guaporensis and 3/3 in O. rioplatensis) and the apex of the hypostome, which is
      more pointed in O. rioplatensis than in O. guaporensis. The Principal Component
      Analysis performed with morphometric characters of larvae showed a clear
      separation among O. guaporensis, O. rioplatensis, O. puertoricensis and O.
      talaje. Significant morphological differences among adults of these four species
      were not found. The analysis of the 16S rDNA sequences allowed for the
      differentiation between O. guaporensis and the remaining Neotropical species of
      the family Argasidae.

PMID- 26217871
TI  - The spider-like katydid Arachnoscelis (Orthoptera: Tettigoniidae:
      Listroscelidinae): anatomical study of the genus.
AB  - This paper provides some observations on the anatomy of the neotropical katydid
      Arachnoscelis arachnoides Karny (Insecta: Orthoptera: Tettigoniidae).
      Arachnoscelis is a genus of predaceous katydids that comprise species that
      resemble spiders in their general body appearance. The type species, A.
      arachnoids, was described in 1891 from a single male collected in Colombia.
      Following the original description, these creatures were never found again, and
      were thought to have gone extinct or mistakenly assigned to the type locality.
      But between 1891 and 2012 four more species were described and in- correctly
      assigned to Arachnoscelis based on a similarity of body form. In this paper we
      present an anatomical comparaison of Arachnoscelis and its relatives, and propose
      that Arachnoscelis should be treated as a monotypic genus. This implies that
      other species previously described in Arachnoscelis, should be placed in
      different genera.

PMID- 26217874
TI  - Larger Descemetorhexis to Improve Graft Adhesion in Descemet Membrane Endothelial
      Keratoplasty Does Not Cause Postoperative Peripheral Corneal Edema.
AB  - PURPOSE: To evaluate the incidence of peripheral corneal edema after Descemet
      membrane endothelial keratoplasty (DMEK) with respect to the size of the
      descemetorhexis. METHODS: A single-center retrospective review of data of 200
      consecutive DMEK surgeries for Fuchs endothelial dystrophy was performed. Forty
      eight eyes of 47 patients were enrolled in this study based on the presence of a
      peripheral zone of free denuded stroma between the margin of the graft and the
      host's Descemet membrane (DM) (group A) or a peripheral overlap between the graft
      and the host's DM (group B). In group A (n=26 eyes), the diameter of the
      descemetorhexis was approximately 10 mm, whereas in group B (n=22 eyes), the
      diameter was approximately 6 mm. Both groups received an 8-mm graft. Main outcome
      measures included peripheral corneal thickness (PCT) at 4 mm from the center,
      central corneal thickness (CCT), central-to-peripheral thickness ratio (CPTR),
      and endothelial cell density (ECD). RESULTS: Mean preoperative PCT+/-SD in group
      A was 728+/-52 MUm and in group B was 708+/-49 MUm (P=0.192). Four weeks after
      DMEK, mean PCT+/-SD was 703+/-43 MUm in group A and 691+/-59 MUm in group B
      (P=0.368). Mean preoperative CCT+/-SD was 642+/-53 MUm and 627+/-58 MUm in groups
      A and B, respectively (P=0.306). There was no significant difference in CCT
      between groups A and B 4 weeks after surgery (P=0.268). Mean preoperative CPTR+/
      SD in group A was 0.88+/-0.05 and in group B was 0.89+/-0.05 (P=0.934). Four
      weeks after DMEK, CPTR was not significantly different between groups A and B
      (P=0.893). There was no significant difference in ECD between groups A and B,
      before and at 4 weeks after DMEK (P=0.093 and P=0.831, respectively).
      CONCLUSIONS: A larger descemetorhexis in DMEK resulting in a peripheral small
      zone of denuded stroma does not increase the incidence of peripheral corneal
      edema as compared with a small descemetorhexis with overlapping DMs.

PMID- 26217877
TI  - Dual-energy computed tomography for monitoring the effect of urate-lowering
      therapy in gouty arthritis.
AB  - OBJECTIVE: To investigate the relationships between changes in serum urate levels
      and dual-energy computed tomography (DE-CT) results during urate-lowering therapy
      (ULT) and to investigate the effects of treatment duration and drugs on changes
      in DE-CT results. METHODS: Forty-four patients diagnosed with gout were enrolled
      in this investigation. DE-CT was conducted on the foot at baseline and the end of
      follow-up (6-24 months). Crystals were classified as: (i) L, number of large
      crystals with diameter >= 3 mm; (ii) S, number of small crystals with diameter <
      3 mm; (iii) T, total number of crystals; and (iv) Vmax, volume of the maximal
      crystal. RESULTS: Number of urate crystals (L, S as well as T) and Vmax decreased
      significantly through ULT. Significant decrease of urate crystal numbers and/or
      Vmax was observed in different follow-up groups, and the decrease in serum urate
      levels was positively related to the decrease of T (r = 0.43, P = 0.04) and Vmax
      (r = 0.63, P = 0.04). Moreover, analysis of covariance results demonstrated
      significant effects of treatment duration and serum urate levels on results of DE
      CT. CONCLUSION: Both urate crystal numbers and Vmax decreased significantly
      during ULT. Additionally, ULT duration and serum urate levels had significant
      effects on the decrease of Vmax and number of large crystals measured by DE-CT.

PMID- 26217876
TI  - Estimated glomerular filtration rate changes in patients with chronic myeloid
      leukemia treated with tyrosine kinase inhibitors.
AB  - BACKGROUND: Chronic use of tyrosine kinase inhibitors (TKIs) may lead to
      previously unrecognized adverse events. This study evaluated the incidence of
      acute kidney injury (AKI) and chronic kidney disease (CKD) in chronic-phase (CP)
      chronic myeloid leukemia (CML) patients treated with imatinib, dasatinib, and
      nilotinib. METHODS: Four hundred sixty-eight newly diagnosed CP CML patients
      treated with TKIs were analyzed. The molecular and cytogenetic response data,
      creatinine, and glomerular filtration rate (GFR) were followed from the start of
      therapy to the last follow-up (median, 52 months). GFR was estimated with the
      Modification of Diet in Renal Disease equation. RESULTS: Nineteen patients (4%)
      had TKI-associated AKI. Imatinib was associated with a higher incidence of AKI in
      comparison with dasatinib and nilotinib (P = .014). Fifty-eight patients (14%)
      developed CKD while they were receiving a TKI; 49 of these patients (84%) did so
      while they were being treated with imatinib (P < .001). Besides imatinib, age, a
      history of hypertension, and diabetes mellitus were also associated with the
      development of CKD. In patients with no CKD at the baseline, imatinib was shown
      to reduce GFR over time. Interestingly, imatinib did not cause a significant
      decline in the GFRs of patients with a history of CKD. Imatinib, dasatinib, and
      nilotinib increased the mean GFR after 3 months of treatment, and nilotinib led
      with the most significant increase (P < .001). AKI or CKD had no significant
      impact on overall cytogenetic and molecular response rates or survival.
      CONCLUSIONS: The administration of TKIs may be safe in the setting of CKD in CP
      CML patients, but close monitoring is still warranted.

PMID- 26217878
TI  - Uncertainty quantification in virtual surgery hemodynamics predictions for single
      ventricle palliation.
AB  - The adoption of simulation tools to predict surgical outcomes is increasingly
      leading to questions about the variability of these predictions in the presence
      of uncertainty associated with the input clinical data. In the present study, we
      propose a methodology for full propagation of uncertainty from clinical data to
      model results that, unlike deterministic simulation, enables estimation of the
      confidence associated with model predictions. We illustrate this problem in a
      virtual stage II single ventricle palliation surgery example. First, probability
      density functions (PDFs) of right pulmonary artery (PA) flow split ratio and
      average pulmonary pressure are determined from clinical measurements,
      complemented by literature data. Starting from a zero-dimensional semi-empirical
      approximation, Bayesian parameter estimation is used to find the distributions of
      boundary conditions that produce the expected PA flow split and average pressure
      PDFs as pre-operative model results. To reduce computational cost, this inverse
      problem is solved using a Kriging approximant. Second, uncertainties in the
      boundary conditions are propagated to simulation predictions. Sparse grid
      stochastic collocation is employed to statistically characterize model
      predictions of post-operative hemodynamics in models with and without PA
      stenosis. The results quantify the statistical variability in virtual surgery
      predictions, allowing for placement of confidence intervals on simulation
      outputs.

PMID- 26217879
TI  - A high sensitive electrochemical aptasensor for the determination of VEGF(165) in
      serum of lung cancer patient.
AB  - Herein, a label free electrochemical aptasensor based on ordered mesoporous
      carbon-gold nanocomposite modified screen printed electrode has been fabricated
      for the detection of vascular endothelial growth factor (VEGF165) as a tumor
      marker. The electrochemical behavior of prepared biosensor was investigated by
      cyclic voltammetry and electrochemical impedance spectroscopy. The principle of
      operation of the proposed aptasensor is based on the changes in the interfacial
      properties of the electrode due to interaction of the immobilized antiVEGF165
      aptamer at the electrode surface with VEGF165 tumor marker in the sample
      solution, which results in a change in the interfacial charge transfer resistance
      as detected by electrochemical impedance spectroscopy. The calibration curve for
      VEGF165 determination was linear over 10.0-300.0 pg mL(-1) with a limit of
      detection (3sigma/S) of 1.0 pg mL(-1). The prepared aptasensor exhibited high
      sensitivity and good selectivity and reproducibility. The aptasensor was
      successfully applied to the determination of VEGF165 in serum sample of a lung
      cancer patient.

PMID- 26217881
TI  - SWI/SNF chromatin remodeling complex regulates a non-chromatin substrate.

PMID- 26217882
TI  - Corrigendum.

PMID- 26217883
TI  - Fish Oil and Impulsive Aggressive Behavior.

PMID- 26217884
TI  - Effects of cattle-slurry treatment by acidification and separation on nitrogen
      dynamics and global warming potential after surface application to an acidic
      soil.
AB  - Cattle-slurry (liquid manure) application to soil is a common practice to provide
      nutrients and organic matter for crop growth but it also strongly impacts the
      environment. The objective of the present study was to assess the efficiency of
      cattle-slurry treatment by solid-liquid separation and/or acidification on
      nitrogen dynamics and global warming potential (GWP) following application to an
      acidic soil. An aerobic laboratory incubation was performed over 92 days with a
      Dystric Cambisol amended with raw cattle-slurry or separated liquid fraction (LF)
      treated or not by acidification to pH 5.5 by addition of sulphuric acid. Soil
      mineral N contents and NH3, N2O, CH4 and CO2 emissions were measured. Results
      obtained suggest that the acidification of raw cattle-slurry reduced
      significantly NH3 emissions (-88%) but also the GWP (-28%) while increased the N
      availability relative to raw cattle-slurry (15% of organic N applied mineralised
      against negative mineralisation in raw slurry). However, similar NH3 emissions
      and GWP were observed in acidified LF and non-acidified LF treatments. On the
      other hand, soil application of acidified cattle-slurry rather than non-acidified
      LF should be preferred attending the lower costs associated to acidification
      compared to solid-liquid separation. It can then be concluded that cattle-slurry
      acidification is a solution to minimise NH3 emissions from amended soil and an
      efficient strategy to decrease the GWP associated with slurry application to
      soil. Furthermore, the more intense N mineralisation observed with acidified
      slurry should lead to a higher amount of plant available N and consequently to
      higher crop yields. 

PMID- 26217885
TI  - A multi-criteria inference approach for anti-desertification management.
AB  - We propose an approach for classifying land zones into categories indicating
      their resilience against desertification. Environmental management support is
      provided by a multi-criteria inference method that derives a set of value
      functions compatible with the given classification examples, and applies them to
      define, for the rest of the zones, their possible classes. In addition, a
      representative value function is inferred to explain the relative importance of
      the criteria to the stakeholders. We use the approach for classifying 28
      administrative regions of the Khorasan Razavi province in Iran into three
      equilibrium classes: collapsed, transition, and sustainable zones. The model is
      parameterized with enhanced vegetation index measurements from 2005 to 2012, and
      7 other natural and anthropogenic indicators for the status of the region in
      2012. Results indicate that grazing density and land use changes are the main
      anthropogenic factors affecting desertification in Khorasan Razavi. The inference
      procedure suggests that the classification model is underdetermined in terms of
      attributes, but the approach itself is promising for supporting the management of
      anti-desertification efforts. 

PMID- 26217886
TI  - Development of nitrogen enriched nanostructured carbon adsorbents for CO2
      capture.
AB  - Nanostructured carbon adsorbents containing high nitrogen content were developed
      by templating melamine-formaldehyde resin in the pores of mesoporous silica by
      nanocasting technique. A series of adsorbents were prepared by altering the
      carbonization temperature from 400 to 700  degrees C and characterized in terms
      of their textural and morphological properties. CO2 adsorption performance was
      investigated at various temperatures from 30 to 100  degrees C by using a
      thermogravimetric analyzer under varying CO2 concentrations. Multiple adsorption
      desorption experiments were also carried out to investigate the adsorbent
      regenerability. X-ray diffraction (XRD) and transmission electron microscopy
      (TEM) confirmed the development of nanostructured materials. Fourier transform
      infrared spectroscopy (FTIR) and elemental analysis indicated the development of
      carbon adsorbents having high nitrogen content. The surface area and pore volume
      of the adsorbent carbonized at 700  degrees C were found to be 266 m(2) g(-1) and
      0.25 cm(3) g(-1) respectively. CO2 uptake profile for the developed adsorbents
      showed that the maximum CO2 adsorption occurred within ca. 100 s. CO2 uptake of
      0.792 mmol g(-1) at 30  degrees C was exhibited by carbon obtained at 700 
      degrees C with complete regenerability in three adsorption-desorption cycles.
      Furthermore, kinetics of CO2 adsorption on the developed adsorbents was studied
      by fitting the experimental data of CO2 uptake to three kinetic models with best
      fit being obtained by fractional order kinetic model with error% within range of
      5%. Adsorbent surface was found to be energetically heterogeneous as suggested by
      Temkin isotherm model. Also the isosteric heat of adsorption for CO2 was observed
      to increase from ca. 30-44 kJ mol(-1) with increase in surface coverage. 

PMID- 26217887
TI  - Biosurfactant from red ash trees enhances the bioremediation of PAH contaminated
      soil at a former gasworks site.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are persistent contaminants that
      accumulate in soil, sludge and on vegetation and are produced through activities
      such as coal burning, wood combustion and in the use of transport vehicles.
      Naturally occurring surfactants have been known to enhance PAH-removal from soil
      by improving PAH solubilization thereby increasing PAH-microbe interactions. The
      aim of this research was to determine if a biosurfactant derived from the leaves
      of the Australian red ash (Alphitonia excelsa) would enhance bioremediation of a
      heavily PAH-contaminated soil and to determine how the microbial community was
      affected. Results of GC-MS analysis show that the extracted biosurfactant was
      significantly more efficient than the control in regards to the degradation of
      total 16 US EPA priority PAHs (78.7% degradation compared to 62.0%) and total
      petroleum hydrocarbons (TPH) (92.9% degradation compared to 44.3%). Furthermore
      the quantification of bacterial genes by qPCR analysis showed that there was an
      increase in the number of gene copies associated with Gram positive PAH-degrading
      bacteria. The results suggest a commercial potential for the use of the
      Australian red ash tree as a source of biosurfactant for use in the accelerated
      degradation of hydrocarbons. 

PMID- 26217889
TI  - Schooling, marriage, and age at first birth in Madagascar.
AB  - The low school attainment, early marriage, and low age at first birth of females
      are major policy concerns in less developed countries. This study jointly
      estimated the determinants of educational attainment, marriage age, and age at
      first birth among females aged 12-25 in Madagascar, explicitly accounting for the
      endogeneities that arose from modelling these related outcomes simultaneously. An
      additional year of schooling results in a delay to marriage of 1.5 years and
      marrying 1 year later delays age at first birth by 0.5 years. Parents' education
      and wealth also have important effects on schooling, marriage, and age at first
      birth, with a woman's first birth being delayed by 0.75 years if her mother had 4
      additional years of schooling. Overall, our results provide rigorous evidence for
      the critical role of education-both individual women's own and that of their
      parents-in delaying the marriage and fertility of young women.

PMID- 26217888
TI  - Biodegradable and conducting hydrogels based on Guar gum polysaccharide for
      antibacterial and dye removal applications.
AB  - Conducting hydrogels possessing antibacterial activity were developed using a two
      step free-radical aqueous polymerization method to incorporate polyaniline chains
      into an adsorbent Guar gum/acrylic acid hydrogel network. The material properties
      of the synthesized samples were characterized using FTIR spectroscopy, thermal
      analysis and scanning electron microscopy techniques. Conducting hydrogels were
      tested for antibacterial activities against gram-positive Staphylococcus aureus
      and gram-negative Escherichia coli bacteria and demonstrated antibacterial
      activity. Synthesized hydrogel samples can be potential adsorbent materials for
      dye removal applications. 

PMID- 26217890
TI  - Natural history of coronary atherosclerosis: did contemporary medical therapy
      change the course?

PMID- 26217891
TI  - Impact of smoking on coronary heart disease: is there a smoker's paradox?

PMID- 26217892
TI  - Clinical characteristics and outcomes in children hospitalised with pandemic
      influenza A/H1N1/09 virus infection - a nationwide survey by the Pediatric
      Infectious Diseases Group of Switzerland.
AB  - OBJECTIVE: To describe all patients admitted to children's hospitals in
      Switzerland with a diagnosis of influenza A/H1N1/09 virus infection during the
      2009 influenza pandemic, and to analyse their characteristics, predictors of
      complications, and outcome. METHODS: All patients <=18-years-old hospitalised in
      eleven children's hospitals in Switzerland between June 2009 and January 2010
      with a positive influenza A/H1N1/09 reverse transcriptase polymerase chain
      reaction (RT-PCR) from a nasopharyngeal specimen were included. RESULTS: There
      were 326 PCR-confirmed patients of whom 189 (58%) were younger than 5 years of
      age, and 126 (38.7%) had one or more pre-existing medical condition. Fever
      (median 39.1  degrees C) was the most common sign (85.6% of all patients), while
      feeding problems (p = 0.003) and febrile seizures (p = 0.016) were significantly
      more frequent in children under 5 years. In 142 (43.6%) patients there was
      clinical suspicion of a concomitant bacterial infection, which was confirmed in
      36 patients (11%). However, severe bacterial infection was observed in 4% of
      patients. One third (n = 108, 33.1%) of the patients were treated with
      oseltamivir, 64 (59.3%, or 20% overall) within 48 hours of onset of symptoms.
      Almost half of the patients (45.1%) received antibiotics for a median of 7 days.
      Twenty patients (6.1%) required intensive care, mostly for complicated pneumonia
      (50%) without an underlying medical condition. The median duration of
      hospitalisation was 2 days (range 0-39) for 304 patients. Two children (<15
      months of age with underlying disease) died. CONCLUSIONS: Although pandemic
      influenza A/H1N1/09 virus infection in children is mostly mild, it can be severe,
      regardless of past history or underlying disease.

PMID- 26217893
TI  - Fibroblast growth factor 23 is associated with the presence of coronary artery
      disease and the number of stenotic vessels.
AB  - Fibroblast growth factor 23 (FGF23) has been reported to be involved in
      cardiovascular disease. The aim of this study was to investigate the association
      between FGF23 and the presence of coronary artery disease (CAD), as well as the
      number of stenotic vessels. A total of 254 eligible participants (167 men and 87
      postmenopausal women) were enrolled in this study. Coronary angiography was used
      for diagnosis of CAD. Serum intact FGF23 levels were determined by a two-sided
      sandwich enzyme-linked immunosorbent assay. The median serum FGF23 levels of the
      entire study population were 39.9 (33.1-47.5) pg/mL. Serum FGF23 levels were
      higher in subjects with one-vessel disease than those without CAD (P < 0.05),
      which further increased significantly in the subjects with multi-vessel disease
      (P < 0.05). Serum FGF23 levels increased with cumulative number of stenotic
      vessels (P for trend < 0.001). Multiple stepwise regression analysis revealed
      estimated glomerular filtration rate (standardized beta = -0.298; P < 0.001) and
      body mass index (standardized beta = 0.132; P = 0.049) were independent factors
      correlated with FGF23. Multivariate logistic regression analysis showed that
      FGF23 was positively and independently associated with the presence of CAD (odds
      ratio = 1.058, 95% confidence interval = 1.025-1.092; P = 0.001). Additionally,
      FGF23 was also correlated with multi-vessel disease significantly (odds ratio =
      1.034, 95% confidence interval = 1.007-1.062; P = 0.013). In conclusion, serum
      FGF23 levels exhibit positive and independent association with the presence of
      CAD and increase with the cumulative number of stenotic vessels. 

PMID- 26217894
TI  - Robust detection of heart beats in multimodal data.
AB  - This editorial reviews the background issues, the design, the key achievements,
      and the follow-up research generated as a result of the PhysioNet/Computing in
      Cardiology (CinC) Challenge 2014, published in the concurrent focus issue of
      Physiological Measurement. Our major focus was to accelerate the development and
      facilitate the comparison of robust methods for locating heart beats in long-term
      multi-channel recordings. A public (training) database consisting of 151 032
      annotated beats was compiled from records that contained ECGs as well as
      pulsatile signals that directly reflect cardiac activity, and other signals that
      may have few or no observable markers of heart beats. A separate hidden test data
      set (consisting of 152 478 beats) is permanently stored at PhysioNet, and a
      public framework has been developed to provide researchers with the ability to
      continue to automatically score and compare the performance of their algorithms.
      A scoring criteria based on the averaging of gross sensitivity, gross positive
      predictivity, average sensitivity, and average positive predictivity is proposed.
      The top three scores (as of March 2015) on the hidden test data set were 93.64%,
      91.50%, and 90.70%. 

PMID- 26217895
TI  - One-step biosynthesis of alpha-ketoisocaproate from L-leucine by an Escherichia
      coli whole-cell biocatalyst expressing an L-amino acid deaminase from Proteus
      vulgaris.
AB  - This work aimed to develop a whole-cell biotransformation process for the
      production of alpha-ketoisocaproate from L-leucine. A recombinant Escherichia
      coli strain was constructed by expressing an L-amino acid deaminase from Proteus
      vulgaris. To enhance alpha-ketoisocaproate production, the reaction conditions
      were optimized as follows: whole-cell biocatalyst 0.8 g/L, leucine concentration
      13.1 g/L, temperature 35  degrees C, pH 7.5, and reaction time 20 h. Under the
      above conditions, the alpha-ketoisocaproate titer reached 12.7 g/L with a leucine
      conversion rate of 97.8%. In addition, different leucine feeding strategies were
      examined to increase the alpha-ketoisocaproate titer. When 13.1 g/L leucine was
      added at 2-h intervals (from 0 to 22 h, 12 addition times), the alpha
      ketoisocaproate titer reached 69.1 g/L, while the leucine conversion rate
      decreased to 50.3%. We have developed an effective process for the
      biotechnological production of alpha-ketoisocaproate that is more environmentally
      friendly than the traditional petrochemical synthesis approach. 

PMID- 26217910
TI  - Silver-Catalyzed Decarboxylative Radical Azidation of Aliphatic Carboxylic Acids
      in Aqueous Solution.
AB  - We report herein an efficient and general method for the decarboxylative
      azidation of aliphatic carboxylic acids. Thus, with AgNO3 as the catalyst and
      K2S2O8 as the oxidant, the reactions of various aliphatic carboxylic acids with
      tosyl azide or pyridine-3-sulfonyl azide in aqueous CH3CN solution afforded the
      corresponding alkyl azides under mild conditions. A broad substrate scope and
      wide functional group compatibility were observed. A radical mechanism is
      proposed for this site-specific azidation. 

PMID- 26217911
TI  - The plant-growth-promoting bacterium Klebsiella sp. SBP-8 confers induced
      systemic tolerance in wheat (Triticum aestivum) under salt stress.
AB  - Plant-growth-promoting bacteria (PGPB) with 1-aminocyclopropane-1
      carboxylatedeaminase (ACCD) activity can protect plants from the deleterious
      effects of abioticstressors. An ACCD bacterial strain, SBP-8, identified as
      Klebsiella sp., also having other plant-growth-promoting activities, was isolated
      from Sorghum bicolor growing in the desertregion of Rajasthan, India. ACCD
      activity of SBP-8 was characterized at biochemical, physiological, and molecular
      levels. The presence of AcdS, a structural gene for ACCD, was confirmed by the
      polymerase chain reaction. Strain SBP-8 showed optimum growth and ACCD activity
      at increased salt (NaCl) concentrations of up to 6%, indicating its potential to
      survive and associate with plants growing in saline soil. Inoculation of wheat
      plants with SBP-8 when grow in the presence of salt (150-200 mM) and temperature
      (30-40  degrees C) stressors resulted inamelioration of stress conditions by
      increasing plant biomass and chlorophyll content, and are duction in plant growth
      inhibition (10-100%) occurred due to salt and temperature stressors. Moreover,
      strain SBP-8 also caused Na(+) exclusion (65%) and increased uptake of K(+)
      (84.21%) in the host plant. This property can protect plants from adverse effects
      of Na(+) on plant growth and physiology. Thus, SBP-8 improves growth of the host
      plant and protects from salt stressors through more than one mechanism including
      an effect of ACCD activity and on K(+)/Na(+) ratio in plants. The colonization
      efficiency of strain SBP-8 was confirmedby CFU (colony-forming unit) count,
      microscopy, and ERIC-PCR based DNA-finger-printing approach. Therefore, and the
      use of efficient colonizing plant-growth-promoting bacteria may provideinsights
      into possible biotechnological approaches to decrease the impact of salinity and
      other stressors.

PMID- 26217912
TI  - Abrupt GaP/GaAs Interfaces in Self-Catalyzed Nanowires.
AB  - We achieve the self-catalyzed growth of pure GaP nanowires and GaAs1-xPx/GaAs1
      yPy nanowire heterostructures by solid-source molecular beam epitaxy. Consecutive
      segments of nearly pure GaAs and GaP are fabricated by commuting the group V
      fluxes. We test different flux switching procedures and measure the corresponding
      interfacial composition profiles with atomic resolution using high-angle annular
      dark field scanning transmission electron microscopy. Interface abruptness is
      drastically improved by switching off all the molecular beam fluxes for a short
      time at the group V commutation. Finally, we demonstrate that the morphology of
      the growth front can be either flat or truncated, depending on the growth
      conditions. The method presented here allows for the facile synthesis of high
      quality GaP/GaAs axial heterostructures directly on Si (111) wafers. 

PMID- 26217913
TI  - Perceptions of self-defined memory problems vary in south Asian minority older
      people who consult a GP and those who do not: a mixed-method pilot study.
AB  - OBJECTIVE: South Asian older adults access services for mental health problems
      and dementia less than other older people in the UK, unlike for physical health
      problems. This pilot study investigated how South Asians with self-defined memory
      problems, with and without GP consultation, construe the symptoms, causes,
      consequences and treatment of the condition. METHODS: Participants were recruited
      through community centres, their networks and memory clinics in Greater
      Manchester. The newly developed Barts Explanatory Model Inventory for Dementia
      (BEMI-D) was administered to 33 (18 M, 15 F) older South Asians aged 65 or above
      with memory problems in English, Gujarati or Urdu. Furthermore, cognition,
      executive function and depression were assessed. RESULTS: Perceptions of dementia
      varied by GP consultation for memory problems. A greater proportion of older
      adults without a consultation considered memory problems to be given by God, saw
      acceptance of fate as an alternative treatment and did not identify medical
      support as appropriate. Forgetfulness and loss of social meaning were identified
      as symptoms of dementia more by those with a consultation. Higher levels of
      diabetes, heart disease and depression were found in those without a
      consultation. CONCLUSIONS: Differences in perceptions may influence the decision
      about consulting a GP. Similarly, consultation for memory problems appears linked
      to extent physical health problems and mental health consultation (depression).
      These variations reported on a small scale in this pilot study suggest the need
      to explore the impact of perceptions on rates of GP consultation, so as to
      improve timely diagnosis and access to appropriate services.

PMID- 26217914
TI  - False aneurysm of perforating branch of the deep femoral artery-Report of two
      cases.
AB  - Pseudoaneurysms of the deep femoral artery are uncommon and occur as a late
      complication of various traumas. Usually associated with femoral fractures, We
      report two cases of profunda femoris artery injury which presented as false
      aneurysm secondary to penetrating trauma. Because of its insidious onset,
      awareness and careful follow-up are the key issues for the early diagnosis. 

PMID- 26217915
TI  - Diffuse intra-abdominal low grade fibromyxoid sarcoma with hepatic metastases:
      Case report and review of the literature.
AB  - INTRODUCTION: Low grade fibromyxoid sarcoma (LGFMS)(1) is a rare soft tissue
      tumor involving deep soft tissues of the extremities and trunk. Abdominal
      location is extremely uncommon in which the few cases published in the literature
      are characterized by slow tumoral progression and long recurrence-free intervals.
      METHODS: We report the first case of an intra-abdominal LGFMS which was
      discovered incidentally in a 42-year-old woman presenting diffuse peritoneal
      nodules and hepatic metastasis on CT and MRI scans. RESULTS: The patient was
      successfully treated through conservative measures and remained asymptomatic at
      the 48 month follow-up. CONCLUSIONS: This is the first reported case of LGFMS
      with peritoneal and hepatic metastases. Despite the discovery of an advance
      disease at exploration, the patient who refused a major surgical operation
      presents an uneventful follow-up and long term survival.

PMID- 26217916
TI  - Using bacterial and necrophagous insect dynamics for post-mortem interval
      estimation during cold season: Novel case study in Romania.
AB  - Considering the biogeographical characteristics of forensic entomology, and the
      recent development of forensic microbiology as a complementary approach for post
      mortem interval estimation, the current study focused on characterizing the
      succession of necrophagous insect species and bacterial communities inhabiting
      the rectum and mouth cavities of swine (Sus scrofa domesticus) carcasses during a
      cold season outdoor experiment in an urban natural environment of Bucharest,
      Romania. We monitored the decomposition process of three swine carcasses during a
      7 month period (November 2012-May 2013) corresponding to winter and spring
      periods of a temperate climate region. The carcasses, protected by wire cages,
      were placed on the ground in a park type environment, while the meteorological
      parameters were constantly recorded. The succession of necrophagous Diptera and
      Coleoptera taxa was monitored weekly, both the adult and larval stages, and the
      species were identified both by morphological and genetic characterization. The
      structure of bacterial communities from swine rectum and mouth tissues was
      characterized during the same time intervals by denaturing gradient gel
      electrophoresis (DGGE) and sequencing of 16S rRNA gene fragments. We observed a
      shift in the structure of both insect and bacterial communities, primarily due to
      seasonal effects and the depletion of the carcass. A total of 14 Diptera and 6
      Coleoptera species were recorded on the swine carcasses, from which Calliphora
      vomitoria and C. vicina (Diptera: Calliphoridae), Necrobia violacea (Coleoptera:
      Cleridae) and Thanatophilus rugosus (Coleoptera: Silphidae) were observed as
      predominant species. The first colonizing wave, primarily Calliphoridae, was
      observed after 15 weeks when the temperature increased to 13 degrees C. This was
      followed by Muscidae, Fanniidae, Anthomyiidae, Sepsidae and Piophilidae. Families
      belonging to Coleoptera Order were observed at week 18 when temperatures raised
      above 18 degrees C, starting with Cleridae, Silphidae, and followed by
      Histeridae, Staphylinidae and Dermestidae. For bacteria, 53 taxa belonging to
      phyla Proteobacteria (Gammaproteobacteria, Betaproteobacteria), Firmicutes and
      Bacteroidetes were identified from the mouth cavity (36 OTUs) and rectum cavity
      (17 OTUs). These shifts in insect and bacterial communities indicated their
      complementary role in the carcass decomposition process. These results represent
      the first forensic entomological and microbiological survey in Romania. This
      study shows the value of forensic entomology as a tool for forensic
      investigations in Romania and neighboring areas with similar biogeographical
      characteristics. Moreover, this study represents a novel approach for
      understanding taphonomy and estimating post-mortem interval during cold season by
      combining entomological and microbiological methods. 

PMID- 26217917
TI  - Enterotoxigenic Escherichia coli Subclinical Infection in Pigs: Bacteriological
      and Genotypic Characterization and Antimicrobial Resistance Profiles.
AB  - Enterotoxigenic Escherichia coli (ETEC) is the major pathogen responsible for
      neonatal diarrhea, postweaning diarrhea, and edema disease in pigs. Although it
      can be harmless, ETEC is also present in the intestines of other animal species
      and humans, causing occasional diarrhea outbreaks. The evaluation of this
      pathogen's presence in food sources is becoming an increasingly important issue
      in human health. In order to determine the prevalence of ETEC in nondiarrheic
      pigs, 990 animals from 11 pig farms were sampled. Using end-time polymerase chain
      reaction (PCR), eltA, estI genes, or both, were detected in 150 (15.2%) animals.
      From the positive samples, 40 (26.6%) ETEC strains were isolated, showing 19
      antibiotic-resistance patterns; 52.5% of these strains had multiple antibiotic
      resistances, and 17.5% carried the intI2 gene. The most prevalent genotypes were
      rfb(O157)/estII/aidA (32.5%) and estI/estII (25.0%). The estII gene was
      identified most frequently (97.5%), followed by estI (37.5%), astA (20.0%), and
      eltA (12.5%). The genes coding the fimbriae F5, F6, and F18 were detected in
      three single isolates. The aidA gene was detected in 20 ETEC strains associated
      with the estII gene. Among the isolated ETEC strains, stx(2e)/estI,
      stx(2e)/estI/estII, and stx(2e)/estI/estII/intI2 genotypes were identified. The
      ETEC belonged to 12 different serogroups; 37.5% of them belonged to serotype
      O157:H19. Isolates were grouped by enterobacterial repetitive intergenic
      consensus-PCR into 5 clusters with 100.0% similarity. In this study, we
      demonstrated that numerous ETEC genotypes cohabit and circulate in swine
      populations without clinical manifestation of neonatal diarrhea, postweaning
      diarrhea, or edema disease in different production stages. The information
      generated is important not only for diagnostic and epidemiological purposes, but
      also for understanding the dynamics and ecology of ETEC in pigs in different
      production stages that can be potentially transmitted to humans from food
      animals.

PMID- 26217918
TI  - DOES CHILDHOOD NUTRITION PREDICT HEALTH OUTCOMES DURING ADULTHOOD? EVIDENCE FROM
      A POPULATION-BASED STUDY IN CHINA.
AB  - Using data collected from the 2008 survey of Internal Migration and Health in
      China, this study examines the impact of late childhood nutrition intakes on a
      wide range of indicators of adult health. The results show that respondents who
      consume rich nutrients (meat, fish, milk, etc.) less frequently during late
      childhood have worse health outcomes when they grow up. They are more likely to
      rate their health as 'fair/poor', report a greater number of chronic diseases,
      have a higher incidence of acute illness, perceive greater numbers of physical
      pains/discomforts and to suffer more from insomnia and depression. With respect
      to objective biometrics, respondents who have less access to rich nutrients at
      age 14 tend to attain a shorter stature, gain more weight as an adult, and are
      more likely to become obese or have low lung capacity. Taken together, the
      evidence in support of a harmful impact of late childhood undernutrition on adult
      health is stronger and more consistent for subjective health indicators than for
      the objective biometrics examined in this study. Moreover, the results also
      indicate that the long-term health impact of late childhood nutrition deprivation
      is especially detrimental for females in China. 

PMID- 26217920
TI  - Competition between Different S-Components for the Shared Energy Coupling Factor
      Module in Energy Coupling Factor Transporters.
AB  - Energy coupling factor (ECF) transporters take up micronutrients in Bacteria and
      Archaea. They consist of a membrane-embedded S-component that provides substrate
      specificity and a three-subunit ECF module that couples ATP hydrolysis to
      transport. The S-components ThiT (for thiamin) and NiaX (for niacin) from
      Lactococcus lactis form complexes with the same ECF module. Here, we assayed the
      uptake of thiamin and niacin in Escherichia coli cells expressing the transporter
      genes. We demonstrate that the two different S-components compete for the ECF
      module, and that competition is more efficient in the presence of the transported
      substrate. The data suggest that binding and release of the S-components is a
      step in the transport cycle.

PMID- 26217919
TI  - Brain plasticity in aphasic patients: intra- and inter-hemispheric reorganisation
      of the whole linguistic network probed by N150 and N350 components.
AB  - The present study examined linguistic plastic reorganization of language through
      Evoked Potentials in a group of 17 non-fluent aphasic patients who had suffered
      left perisylvian focal lesions, and showed a good linguistic recovery. Language
      reorganisation was probed with three linguistic tasks (Phonological, Semantic,
      Orthographic), the early word recognition potential (N150) and the later
      phonological-related component (N350). Results showed the typical left
      lateralised posterior N150 in healthy controls (source: left Fusiform Gyrus),
      that was bilateral (Semantic) or right sided (Phonological task) in patients
      (sources: right Inferior/Middle Temporal and Fusiform Gyri). As regards N350,
      controls revealed different intra- and inter-hemispheric linguistic activation
      across linguistic tasks, whereas patients exhibited greater activity in left
      intact sites, anterior and posterior to the damaged area, in all tasks (sources:
      Superior Frontal Gyri). A comprehensive neurofunctional model is presented,
      describing how complete intra- and inter-hemispheric reorganisation of the
      linguistic networks occurs after aphasic damage in the strategically dominant
      left perisylvian linguistic centres. 

PMID- 26217921
TI  - Effectiveness, tolerability and acceptance of a low-dosed estradiol/dienogest
      formulation (Lafamme 1 mg/2 mg) for the treatment of menopausal complaints: a non
      interventional observational study over 6 cycles of 28 days.
AB  - BACKGROUND: Concern and controversy characterize nowadays the use of hormone
      therapy for management of patients with menopausal complaints. This observational
      non-interventional study examined the use of a marketed oral formulation
      containing 1 mg estradiol valerate and 2 mg dienogest for treatment of menopausal
      symptoms in 1292 women visiting 243 gynecological practices in Germany. METHODS:
      Score changes in the Menopausal Rating Scale (MRS) after three and six 28-day
      cycles were primary endpoints. Subjective reports on skin- and hair-related
      complaints and satisfaction with treatment effects were assessed. The incidence
      of adverse drug reactions (ADRs), adverse events (AEs) and vaginal bleeding was
      evaluated. RESULTS: MRS total score decreased substantially and stronger than the
      clinically relevant change of 5 points (p < 0.0001) as compared with baseline.
      Subjective skin- and hair-related complaints declined. No unexpected ADRs were
      reported. AEs (including ADRs) were registered in 8.8% of the participants; most
      frequent AEs/ADRs were postmenopausal hemorrhage (2.9%) and drug ineffective
      (1.4%). Nearly 76% of the subjects remained amenorrheic. Approximately 90% of the
      patients rated the medication's effectiveness/tolerability as good/very good; 84%
      intended to continue the treatment. CONCLUSION: This low-dose estradiol/dienogest
      formulation proved efficient and well-tolerated option for the alleviation of
      menopausal symptoms associated with estrogen deficiency.

PMID- 26217923
TI  - Respiratory and Muscular Perceived Exertion During Official Games in Professional
      Soccer Players.
AB  - PURPOSE: The aim of this study was to assess the respiratory and muscular session
      ratings of perceived exertion (PE) after official soccer matches over an extended
      period of time (ie, 2 competition seasons) in relation to playing time (>20, 20
      45, 45-70, and >70 min) and to determine the between-matches variability of both
      scores in young professional soccer players. METHODS: Forty players belonging to
      the same reserve team of a Spanish La Liga club participated in this study.
      Respiratory and muscular PE were collected 10 min after every game. A total of
      841 individual PE ratings were undertaken on outfield players. RESULTS: The
      differences between match respiratory and muscular load differ depending on the
      playing time, the respiratory PE being greater for the players that competed less
      than 45 min (effect size = -0.45 +/- 0.45 for the 20- to 45-min group) and the
      muscular PE greater for players that played more than 45 min (effect size = 0.23
      +/- 0.30, for the 45- to 70-min group). Match-to-match PE variability was
      considerable (CV = 14-54%) for all levels of participation, but it was lower the
      longer the players participated. CONCLUSIONS: Playing time influenced the
      relative exertion that players' respiratory and leg musculature were exposed to
      during a game, suggesting that differential PE scores might provide a more
      accurate evaluation of match-imposed internal load. However, the small-magnitude
      differences between respiratory and muscular session ratings of PE observed in
      the current study might question the practical relevance of assessing both
      scores.

PMID- 26217922
TI  - Prediction model for regional or distant recurrence in endometrial cancer based
      on classical pathological and immunological parameters.
AB  - BACKGROUND: Adjuvant therapy increases disease-free survival in endometrial
      cancer (EC), but has no impact on overall survival and negatively influences the
      quality of life. We investigated the discriminatory power of classical and
      immunological predictors of recurrence in a cohort of EC patients and confirmed
      the findings in an independent validation cohort. METHODS: We reanalysed the data
      from 355 EC patients and tested our findings in an independent validation cohort
      of 72 patients with EC. Predictors were selected and Harrell's C-index for
      concordance was used to determine discriminatory power for disease-free survival
      in the total group and stratified for histological subtype. RESULTS: Predictors
      for recurrence were FIGO stage, lymphovascular space invasion and numbers of
      cytotoxic and memory T-cells. For high risk cancer, cytotoxic or memory T-cells
      predicted recurrence as well as a combination of FIGO stage and lymphovascular
      space invasion (C-index 0.67 and 0.71 vs 0.70). Recurrence was best predicted
      when FIGO stage, lymphovascular space invasion and numbers of cytotoxic cells
      were used in combination (C-index 0.82). Findings were confirmed in the
      validation cohort. CONCLUSIONS: In high-risk EC, clinicopathological or
      immunological variables can predict regional or distant recurrence with equal
      accuracy, but the use of these variables in combination is more powerful.

PMID- 26217924
TI  - Characteristics of women with repeat termination of pregnancy: a study of all
      requests for pregnancy termination in Norway during 2007-2011.
AB  - INTRODUCTION: We studied the proportion of all pregnancy terminations requested
      by women with a history of pregnancy termination. We also studied risk factors
      for repeat pregnancy termination. MATERIAL AND METHODS: We used data from the
      Norwegian Register of Pregnancy Termination during the period 2007-2011, a total
      of 80,346 requests for pregnancy termination before the end of the 12th
      gestational week. Odds ratios for repeat pregnancy termination were estimated
      according to age, parity, contraceptive use, marital status, education,
      employment status and region of residency by applying logistic regression
      analyses. Repeat pregnancy termination was defined as request for pregnancy
      termination for the second time or more. RESULTS: Among the 80 346 requests for
      pregnancy termination, 36.7% were among women with a history of pregnancy
      termination. In total, 25.0% had one prior termination and 11.7% had two or more.
      Factors associated with repeat pregnancy termination were; age >=25 years, having
      one or more children, and use of contraception at the time of conception.
      College/university education as compared with primary school only, was associated
      with reduced risk of repeat termination. CONCLUSION: Among all requests for
      pregnancy termination in Norway, 36.7% were from women with a history of
      pregnancy termination. Many women with repeat pregnancy termination have children
      and/or used contraception at the time of conception. Our findings therefore
      suggest that high fecundity is an underlying risk factor for repeat pregnancy
      termination.

PMID- 26217925
TI  - Six-Year Clinical Outcomes After Catheter Ablation of Atrial Fibrillation in
      Patients With Impaired Left Ventricular Function.
AB  - INTRODUCTION: Long-term data after pulmonary vein isolation (PVI) in patients
      with impaired systolic left ventricular ejection fraction (LVEF) are sparse. This
      study assessed the outcomes in patients with atrial fibrillation (AF) and reduced
      LVEF treated with PVI after a median follow-up period of 6 years. METHODS AND
      RESULTS: Eighty-one patients with an LVEF<=45% were evaluated; however, 1 patient
      was lost to follow-up. In the remaining 80 patients (male: n = 68 (85%), median
      age 61.6 (54.8-67.5) years) with paroxysmal (n = 16, 20%), persistent (n = 37,
      46.2%), and longstanding-persistent AF (LS-AF), catheter ablation of AF using
      radiofrequency and 3D mapping was performed. Follow-up included Holter monitoring
      or pacemaker/ICD interrogation to assess for arrhythmia recurrence and
      echocardiography to assess LVEF. Median follow-up was 72 (67-75) months. Death
      occurred in 21 patients. Single-procedure success rate was 35.1% and multiple
      procedure success rate was 56.8% in the overall group. Baseline median LVEF (35%
      [28.5-40%]) significantly increased at 6-year follow-up (56.5% [40.0-60.0%], P <
      0.01). In patients with single- or multiple-procedure ablation success, there was
      a higher improvement of LVEF (single procedure: 25% [15.0-35] vs. 10.0% [-1.0
      20.0], P < 0.01; multiple procedures: 20.0% [15-34] vs. 5.0% [5.00-15.0]; P <
      0.01). The single (43.8% vs. 40%, P = 0.96) and multiple procedure success rates
      (62.5% vs. 60%, P = 0.47) were comparable between patients with PAF and
      persistent AF and lowest in patients with LS-AF (single procedure success: 23.1%,
      multiple-procedure success: 47.8%). CONCLUSION: Single-procedure success rates
      after PVI during 6 years of follow-up were low. In patients with single- or
      multiple-procedure ablation success, a higher improvement of LVEF was observed.

PMID- 26217926
TI  - Prevalence and Characteristics of Discogenic Pain in Tertiary Practice: 223
      Consecutive Cases Utilizing Lumbar Discography.
AB  - BACKGROUND: Between 26% and 42% of chronic low back pain is attributed to
      internal disc disruption of lumbar intervertebral discs. These prevalence
      estimates and data characterizing discogenic pain originate largely from research
      at elite practices, conducted 20 years ago. With few studies since, their
      concordance with rates in community practice has rarely been addressed.
      OBJECTIVE: To assess the prevalence and key features of discogenic pain within
      community-based tertiary practice, and to evaluate the accuracy and clinical
      utility of discography. DESIGN: This prospective, three-year study of 223
      consecutive cases of chronic low back pain used image-guided lumbar discography
      to identify symptomatic and flanking asymptomatic discs. A subset of patients (n
      = 195) had previously undergone posterior column blocks to investigate spinal
      facet and/or sacroiliac joints as contributing pain sources. RESULTS: A total of
      644 discs were tested without infection or complication. Positive discograms were
      recorded in 74% of patients, with 22.9% negative and 3.1% assessed as
      indeterminate. Among patients receiving both discography and diagnostic blocks,
      63% had proven discogenic pain, 18% had pain of mixed etiology and 14% remained
      undiagnosed. Taking into account all low back pain cases during this study (n =
      756), discogenic pain prevalence was 21.8% (95% CI: 17-26%). CONCLUSION: The
      prevalence of discogenic pain in this community practice is below the range, but
      within confidence intervals, previously reported. Prevalence is considerably
      elevated, however, among well-selected patients and discography enabled a firm
      diagnosis in most such cases. These findings are broadly in keeping with those
      reached in key publications and support the clinical utility of discography.

PMID- 26217927
TI  - Partially Evoked Epithelial-Mesenchymal Transition (EMT) Is Associated with
      Increased TGFbeta Signaling within Lesional Scleroderma Skin.
AB  - The origin of myofibroblasts in fibrotic conditions remains unknown and in
      systemic sclerosis (SSc) it has been proposed that activation of local
      fibroblasts, trans-differentiation of perivascular or vascular cells, recruitment
      of fibrocyte progenitors, or epithelial to mesenchymal transition (EMT) could be
      contributing. Data from our laboratory indicate that the epidermis in scleroderma
      is activated with the keratinocytes exhibiting a phenotype normally associated
      with tissue repair, including phosphorylation profiles indicative of TGFbeta
      signaling. Since TGFbeta is a known inducer of EMT, we investigated if there is
      evidence of this process in the SSc epidermis. In order to validate antibodies
      and primers, EMT was modeled in HaCaT cells cultured in the presence of TGFbeta1.
      Skin sections were stained with phosho-SMAD2/3, as well as with epithelial and
      mesenchymal markers. Moreover, mRNA levels of transcription factors associated
      with EMT were studied in epidermal blister sheets. We observed critical changes
      in the scleroderma epidermis; showing significantly increased nuclear
      translocation of phosphorylated Smad2/3, consistent with active TGFbeta signaling
      in SSc keratinocytes. While profound EMT could be induced in keratinocytes in
      vitro with the appearance of SNAI1/2 and FSP-1, and an accompanying loss of E
      cadherin, in the scleroderma skin active TGFbeta signaling was accompanied by
      only partial EMT-like changes characterised by induction of SNAI1 alone and with
      no loss of E-cadherin. Together, our findings support a model of altered
      differentiation and TGFbeta dependent activation of scleroderma epithelial cells
      leading to a partially evoked EMT like process in the fibrotic skin. 

PMID- 26217928
TI  - Misuse of prescription stimulant medication in a sample of college students:
      examining differences between varsity athletes and non-athletes.
AB  - BACKGROUND: The misuse of prescription stimulants (MPS) has been identified as an
      adverse health behavior among college students. Because stimulant medication is
      often taken to increase focus and decrease reaction time, these substances have
      the potential to enhance athletic performance. However, the role that athlete
      status (varsity athlete vs. non-athlete) has on MPS has rarely been examined in
      the college student population. OBJECTIVES: To examine whether there are
      differences in past-year MPS and MPS-related motivations between college varsity
      athletes and non-athletes. METHODS: A sample of 682 (482 non-athletes; 200
      athletes) college students between the ages of 18 and 25 completed a paper-based
      questionnaire to assess MPS, MPS-related motivations, and other potential MPS
      correlates (e.g., gender, energy drink consumption, tobacco use, heavy episodic
      drinking). Then, we conducted bivariate and multivariate analyses to examine
      potential correlates of MPS, including athlete status. Finally, we examined
      differences in MPS-related motivations between varsity athletes and non-athletes.
      RESULTS: Overall, 98 (13.9%; 16.6% non-athletes v. 7.5% varsity athletes)
      respondents reported past-year MPS and varsity athletes were significantly less
      likely (p<0.05) to do so. Past-year MPS was also significantly associated with
      energy drink consumption, tobacco use, and heavy episodic drinking in our sample.
      Concerning MPS-related motivations, athletes more often cited a need to enhance
      athletic performance as the impetus for their misuse. CONCLUSIONS: MPS was
      prevalent among the sample. Varsity athletes were significantly less likely to
      engage in past-year MPS and were motivated to do so for different reasons.

PMID- 26217930
TI  - Evaluation of Pharmacy-Based HIV Testing in a High-Risk New York City Community.
AB  - Blacks/Hispanics face limited access to HIV testing. We examined in-pharmacy HIV
      testing among customers in pharmacies participating in a nonprescription syringe
      program in New York City. Participants were recruited in two pharmacies to
      complete a survey and receive an optional HIV test. Bivariate and multivariable
      analyses were performed to examine associations of demographics and risk
      behaviors with receiving in-pharmacy HIV testing. Most participants were male
      (55%), black (80%), had used hard drugs (88%), and 39.5% received in-pharmacy HIV
      testing. Being female (AOR=2.24; 95%CI 1.24-4.05), having multiple sex partners
      (AOR=1.20; 95% CI 1.06-1.35), having an HIV test more than 12 months ago
      (AOS=4.06; CI 1.85-8.91), injecting drugs in last 3 months (AOR=2.73; 95% CI 1.31
      5.69) and having continuous care (AOR=0.32; 95% CI 0.17-0.58) were associated
      with receiving in-pharmacy HIV test. These data provide evidence of in-pharmacy
      HIV testing reaching persons at risk of HIV. HIV testing in pharmacies may
      complement existing strategies. 

PMID- 26217929
TI  - The relationship between electronic goal reminders and subsequent drug use and
      treatment initiation in a criminal justice setting.
AB  - INTRODUCTION: Opportunities to influence behavior through the use of electronic
      reminders has not been examined in a criminal justice population. The purpose of
      this study was to assess probationer preferences for short-term goals from a web
      based program and evaluate the role of voluntary electronic reminders (e.g., text
      messaging, email) in achieving early treatment and probation tasks. METHODS: We
      used data from drug-involved offenders (n=76) participating in a clinical trial
      of a 2-session motivational computer program. As part of the program,
      participants could choose to receive text or email reminders about their
      probation and treatment goals for the next month. Poisson regression models were
      utilized to evaluate goal and reminder selection in relation to the days of
      substance use and treatment attendance at two-month follow-up. RESULTS: The most
      common goals were related to probation and treatment tasks, relationships, and
      cognitive reappraisals. Forty-five percent of probationers elected to receive
      electronic goal reminders at Session 1 with a slight increase at Session two
      (49%). Probationers who opted to receive electronic goal reminders at Session one
      selected significantly more goals on average (M=4.4, SD=2.1) than probationers
      who did not want reminders (M=3.4, SD=1.8), (t=2.41, p=.019). Reminder selection
      and total number of goals selected predicted days of substance use and treatment
      attendance at a two-month follow-up. Probationers who opted not to receive
      electronic reminders and those who only chose to receive reminders at one visit
      had more days of substance use compared to those who chose to receive reminders
      at both visits, 1.66 and 2.31 times respectively. Probationers who chose not to
      receive electronic reminders attended 56% fewer days of treatment compared to
      those who chose to receive reminders at both visits. CONCLUSIONS: People's choice
      of short-term goals and reminders can provide advance notification of the
      likelihood of substance use and treatment initiation. Probation systems might use
      such information to triage at-risk probationers to a higher level of service,
      before problems have emerged.

PMID- 26217931
TI  - Behavioral Interventions Improve Condom Use and HIV Testing Uptake Among Female
      Sex Workers in China: A Systematic Review and Meta-Analysis.
AB  - Condomless commercial sex work is a common mode of HIV transmission in China.
      This study systematically reviews the impacts of behavioral interventions on
      condom use and HIV testing uptake among female sex workers (FSW) in China.
      Chinese and English language peer-reviewed articles published between January
      2000 and December 2013 were searched in five electronic databases. Odds ratios
      (OR) were calculated by comparing the levels of improvements in condom use and
      HIV testing uptake by various intervention strategies. Study quality was assessed
      for included studies. This review followed the PRISMA guidelines and was
      registered in PROSPERO. One hundred and twenty-eight studies met inclusion
      criteria. Meta-analyses indicated that FSW in the post-intervention period were
      2.3-5.0 times more likely to use condoms with male clients in their last sexual
      act and 2.3-3.4 times more likely to use condoms consistently in the last month
      than in the pre-intervention period. In particular, multiple session intervention
      were more effective in improving condom use among FSW with male clients (OR=5.6,
      [4.0-7.8]) than a single session intervention (OR=3.3, [2.8-3.8]). Behavioral
      interventions also improved past-12-month HIV testing uptake 4.6-fold (95% CI,
      2.9-7.4). Comprehensive intervention programs were more effective (OR=8.1, [4.0
      16.7]) in improving HIV testing uptake compared with health education only
      programs (OR=2.7, [1.6-4.5]). Longer intervention duration (>12 months) did not
      increase effectiveness in improving condom use or HIV testing rate among Chinese
      FSWs. Behavioral interventions are effective in improving condom use and HIV
      testing uptake among Chinese FSW. This review highlights both the potentials and
      limitations of condom promotion interventions targeting female sex workers. 

PMID- 26217932
TI  - Quantitative and morphological study of intraepidermal nerve fibre in healthy
      individuals.
AB  - The study was aimed to observe the morphology of intraepidermal nerve fibre
      (IENF) and to explore the relationships between intraepidermal nerve fibre
      density (IENFD) and anatomic sites, age, genders and races. Intraepidermal nerve
      fibre was observed using immunohistochemistry. The relationships between IENFD
      and anatomic sites, ages, genders and races were analysed by quantitative
      analysis of IENFD. Five patterns of the IENFs were observed according to the
      morphological classification. A significant difference was observed in IENFD
      between different anatomic sites (P < 0.05). A linear negative correlation was
      observed between IENFD and age (r = - 0.2931, P < 0.01). No significant
      difference was found between IENFD and genders. Intraepidermal nerve fibre
      density at distal leg of Chinese (395.54 +/- 166.92) was higher than that of
      Finnish (114.62 +/- 32.32, P < 0.01). Skin biopsy may be an effective tool in
      quantitation of IENFD in healthy individuals. Intraepidermal nerve fibre density
      is independent of genders, and closely associated with anatomic sites, races and
      ages. 

PMID- 26217934
TI  - Test-retest reliability of computer-based video analysis of general movements in
      healthy term-born infants.
AB  - BACKGROUND: A computer-based video analysis has recently been presented for
      quantitative assessment of general movements (GMs). This method's test-retest
      reliability, however, has not yet been evaluated. AIMS: The aim of the current
      study was to evaluate the test-retest reliability of computer-based video
      analysis of GMs, and to explore the association between computer-based video
      analysis and the temporal organization of fidgety movements (FMs). STUDY DESIGN:
      Test-retest reliability study. SUBJECTS: 75 healthy, term-born infants were
      recorded twice the same day during the FMs period using a standardized video set
      up. OUTCOME MEASURES: The computer-based movement variables "quantity of motion
      mean" (Qmean), "quantity of motion standard deviation" (QSD) and "centroid of
      motion standard deviation" (CSD) were analyzed, reflecting the amount of motion
      and the variability of the spatial center of motion of the infant, respectively.
      In addition, the association between the variable CSD and the temporal
      organization of FMs was explored. Intraclass correlation coefficients (ICC 1.1
      and ICC 3.1) were calculated to assess test-retest reliability. RESULTS: The ICC
      values for the variables CSD, Qmean and QSD were 0.80, 0.80 and 0.86 for ICC
      (1.1), respectively; and 0.80, 0.86 and 0.90 for ICC (3.1), respectively. There
      were significantly lower CSD values in the recordings with continual FMs compared
      to the recordings with intermittent FMs (p<0.05). CONCLUSION: This study showed
      high test-retest reliability of computer-based video analysis of GMs, and a
      significant association between our computer-based video analysis and the
      temporal organization of FMs.

PMID- 26217933
TI  - Decreasing-Rate Pruning Optimizes the Construction of Efficient and Robust
      Distributed Networks.
AB  - Robust, efficient, and low-cost networks are advantageous in both biological and
      engineered systems. During neural network development in the brain, synapses are
      massively over-produced and then pruned-back over time. This strategy is not
      commonly used when designing engineered networks, since adding connections that
      will soon be removed is considered wasteful. Here, we show that for large
      distributed routing networks, network function is markedly enhanced by hyper
      connectivity followed by aggressive pruning and that the global rate of pruning,
      a developmental parameter not previously studied by experimentalists, plays a
      critical role in optimizing network structure. We first used high-throughput
      image analysis techniques to quantify the rate of pruning in the mammalian
      neocortex across a broad developmental time window and found that the rate is
      decreasing over time. Based on these results, we analyzed a model of
      computational routing networks and show using both theoretical analysis and
      simulations that decreasing rates lead to more robust and efficient networks
      compared to other rates. We also present an application of this strategy to
      improve the distributed design of airline networks. Thus, inspiration from neural
      network formation suggests effective ways to design distributed networks across
      several domains. 

PMID- 26217935
TI  - Nucleated red blood cells as marker for an increased risk of unfavorable outcome
      and mortality in very low birth weight infants.
AB  - BACKGROUND: Nucleated red blood cells (NRBC) are normoblastic cells that failed
      to extrude their nuclei before exiting from bone marrow or liver. While NRBC are
      frequently found in umbilical cord blood after fetal distress, NRBC counts drop
      rapidly after birth. AIMS: To determine the predictive value of the NRBC count
      during the first 120h after birth as marker for later risk of unfavorable outcome
      in very preterm infants. STUDY DESIGN: This cohort study investigated the
      association between absolute count of NRBC on admission (day 1), the mean NRBC
      count between day 2 to 5, and outcome (mortality or the composite outcome of
      mortality and severe morbidity). RESULTS: 438 infants with a gestational
      age<32weeks and a birth weight<1500g were included within a five-year period, of
      whom 46 patients died and 65 suffered from severe morbidity. Nonsurvivors had
      significantly higher NRBC counts between day 2 and 5, as compared to survivors.
      This finding was observed in infants both appropriate and small for gestational
      age. An increase of 10/nL of the mean NRBC count on postnatal day 2 to 5 had an
      odds ratio for mortality of 6.95 (95% CI 2.21-21.86) and an odds ratio for the
      composite outcome mortality and severe morbidity of 3.43 (95% CI 1.43-8.24). The
      optimal cut-off value for prediction of death was NRBC >2/nL with a sensitivity
      of 85% and a specificity of 75%. CONCLUSIONS: Elevation of NRBC on postnatal day
      2 to 5 is an independent predictor of mortality in preterm infants.

PMID- 26217936
TI  - The effect of caffeine citrate on neural breathing pattern in preterm infants.
AB  - BACKGROUND: Caffeine citrate is widely used to prevent and treat prematurity
      associated apnea. AIMS: The aim of this study was to characterize the effect of
      caffeine citrate on the neural control of breathing, especially central apnea, in
      premature infants. STUDY DESIGN: Preterm infants were evaluated for 30min before
      and 30min after caffeine citrate loading (20mg/kg). A feeding tube including
      miniaturized sensors was used to measure the diaphragm electrical activity (Edi)
      waveform. Central apnea was defined as any period where the Edi waveform was flat
      for >5s. SUBJECTS: Seventeen preterm infants with a mean age of three days and
      mean birth weight of 900 grams were evaluated. OUTCOME MEASURES: In addition to
      central apnea, several parameters including neural inspiratory time, neural
      respiratory rate, peak Edi, delta inspiratory change in Edi (phasic Edi) and
      minimum Edi on exhalation were measured. RESULTS: The majority of the apnea were
      short (5 to 10s) and the number of apnea correlated with birth weight (p=0.039).
      Caffeine citrate reduced significantly the number of 5-to-10-second-long central
      apnea during the 30-minute periods (12+/-11 to 7+/-7; p=0.02). Caffeine citrate
      increased both peak and phasic Edi leading to a significant increase in the
      diaphragm energy expenditure. CONCLUSIONS: Edi signal can be reliably measured
      and processed to study changes in premature infants' neural breathing. The
      beneficial effect of caffeine citrate on the reduction of the number of apnea is
      mediated through stimulated neural breathing increasing the diaphragm energy
      expenditure.

PMID- 26217937
TI  - N-BiPAP treatment in infants with respiratory distress syndrome: A population
      study.
AB  - BACKGROUND: Since November 1st 2008, our Norwegian neonatal intensive care unit
      has used nasal biphasic positive airway pressure (n-BiPAP) instead of invasive
      mechanical ventilation as first-line treatment after nasal continuous positive
      airway pressure (n-CPAP) failure in infants with respiratory distress syndrome
      (RDS). AIM: To assess utility of a national patient register to compare outcomes
      of infants in our unit before and after November 1st 2008 as well as to hospitals
      that did not utilize n-BiPAP during the observation period. STUDY DESIGN: A
      retrospective study, using a national patient register and a difference-in
      difference (DID) statistical approach, adjusting for confounders. SUBJECTS:
      Infants with RDS admitted to hospital 2002-2010. OUTCOME MEASURES: We compared
      our unit before and after November 1st 2008 and to other hospitals with regards
      to morbidity, mortality, and number of hospital days (NHD). RESULTS: Infants with
      RDS in our unit had a significantly lower risk of bronchopulmonary dysplasia
      (BPD) (odds ratio (OR) 0.59, p<0.05), retinopathy of prematurity (ROP) (OR 0.57,
      p<0.05), and intraventricular hemorrhage (IVH) (OR 0.37, p<0.001); as well as the
      combined outcome of periventricular leukomalacia (PVL), necrotizing enterocolitis
      (NEC), ROP, IVH, and/or BPD (OR 0.53, p<0.05) after November 1st 2008 and
      compared to other hospitals. PVL, NEC, and mortality did not change. NHD was
      reduced by 8. CONCLUSION: Increasing use of n-BiPAP was associated with reduced
      morbidity and NHD in infants with RDS. Using a patient register and DID analyses
      may be a health economic and ethically sound way of generating hypotheses and
      knowledge about disease and treatment.

PMID- 26217938
TI  - BMP-2 Induced Expression of PLCbeta1 That is a Positive Regulator of Osteoblast
      Differentiation.
AB  - Bone morphogenetic protein 2 (BMP-2) is a critical growth factor that directs
      osteoblast differentiation and bone formation. Phosphoinositide-phospholipase
      Cbeta 1 (PLCbeta1) plays a crucial role in the initiation of the genetic program
      responsible for muscle differentiation. Differentiation of C2C12 mouse myoblasts
      in response to insulin stimulation is characterized by a marked increase in
      nuclear PLCbeta1. Here, the function of PLCbeta1 in the osteogenic
      differentiation was investigated. Briefly, in C2C12 cells treated with BMP-2 we
      assist to a remarkable increase in PLCbeta1 protein and mRNA expression. The data
      regarding the influence on differentiation demonstrated that PLCbeta1 promotes
      osteogenic differentiation by up-regulating alkaline phosphatase (ALP). Moreover,
      PLCbeta1 is present in the nuclear compartment of these cells and overexpression
      of a cytosolic-PLCbeta1mutant (cyt-PLCbeta1), which lacks a nuclear localization
      sequence, prevented the differentiation of C2C12 cells into osteocytes. Recent
      evidence indicates that miRNAs act as important post transcriptional regulators
      in a large number of processes, including osteoblast differentiation. Since miR
      214 is a regulator of Osterix (Osx) which is an osteoblast-specific transcription
      factor that is needful for osteoblast differentiation and bone formation, we
      further investigated whether PLCbeta1 could be a potential target of miR-214 in
      the control of osteogenic differentiation by gain- and loss- of function
      experiment. The results indicated that inhibition of miR-214 in C2C12 cells
      significantly enhances the protein level of PLCbeta1 and promotes C2C12 BMP-2
      induced osteogenesis by targeting PLCbeta1.

PMID- 26217939
TI  - Solution-Processed CoFe2O4 Nanoparticles on 3D Carbon Fiber Papers for Durable
      Oxygen Evolution Reaction.
AB  - We report CoFe2O4 nanoparticles (NPs) synthesized using a facile hydrothermal
      growth and their attachment on 3D carbon fiber papers (CFPs) for efficient and
      durable oxygen evolution reaction (OER). The CFPs covered with CoFe2O4 NPs show
      orders of magnitude higher OER performance than bare CFP due to high activity of
      CoFe2O4 NPs, leading to a small overpotential of 378 mV to get a current density
      of 10 mA/cm(2). Significantly, the CoFe2O4 NPs-on-CFP electrodes exhibit
      remarkably long stability evaluated by continuous cycling (over 15 h) and
      operation with a high current density at a fixed potential (over 40 h) without
      any morphological change and with preservation of all materials within the
      electrode. Furthermore, the CoFe2O4 NPs-on-CFP electrodes also exhibit hydrogen
      evolution reaction (HER) performance, which is considerably higher than that of
      bare CFP, acting as a bifunctional electrocatalyst. The achieved results show
      promising potential for efficient, cost-effective, and durable hydrogen
      generation at large scales using earth-abundant materials and cheap fabrication
      processes. 

PMID- 26217940
TI  - Patient-Derived Gastric Carcinoma Xenograft Mouse Models Faithfully Represent
      Human Tumor Molecular Diversity.
AB  - Patient-derived cancer xenografts (PDCX) generally represent more reliable models
      of human disease in which to evaluate a potential drugs preclinical efficacy.
      However to date, only a few patient-derived gastric cancer xenograft (PDGCX)
      models have been reported. In this study, we aimed to establish additional PDGCX
      models and to evaluate whether these models accurately reflected the histological
      and genetic diversities of the corresponding patient tumors. By engrafting fresh
      patient gastric cancer (GC) tissues into immune-compromised mice (SCID and/or
      nude mice), thirty two PDGCX models were established. Histological features were
      assessed by a qualified pathologist based on H&E staining. Genomic comparison was
      performed for several biomarkers including ERBB1, ERBB2, ERBB3, FGFR2, MET and
      PTEN. These biomarkers were profiled to assess gene copy number by fluorescent in
      situ hybridization (FISH) and/or protein expression by immunohistochemistry
      (IHC). All 32 PDGCX models retained the histological features of the
      corresponding human tumors. Furthermore, among the 32 models, 78% (25/32) highly
      expressed ERBB1 (EGFR), 22% (7/32) were ERBB2 (HER2) positive, 78% (25/32) showed
      ERBB3 (HER3) high expression, 66% (21/32) lost PTEN expression, 3% (1/32)
      harbored FGFR2 amplification, 41% (13/32) were positive for MET expression and
      16% (5/32) were MET gene amplified. Between the PDGCX models and their parental
      tumors, a high degree of similarity was observed for FGFR2 and MET gene
      amplification, and also for ERBB2 status (agreement rate = 94~100%; kappa value =
      0.81~1). Protein expression of PTEN and MET also showed moderate agreement
      (agreement rate = 78%; kappa value = 0.46~0.56), while ERBB1 and ERBB3 expression
      showed slight agreement (agreement rate = 59~75%; kappa value = 0.18~0.19). ERBB2
      positivity, FGFR2 or MET gene amplification was all maintained until passage 12
      in mice. The stability of the molecular profiles observed across subsequent
      passages within the individual models provides confidence in the utility and
      translational significance of these models for in vivo testing of personalized
      therapies. 

PMID- 26217941
TI  - Rat Model of Parkes Weber Syndrome.
AB  - The Parkes Weber syndrome is a congenital vascular malformation, characterized by
      varicose veins, arterio-venous fistulas and overgrown limbs. No broadly accepted
      animal model of Parkes Weber syndrome has been described. We created side-to-side
      arterio-venous fistula between common femoral vessels with proximal non
      absorbable ligature on common femoral vein limiting the enlargement of the vein
      diameter in Wistar rats. Contralateral limb was sham operated. Invasive blood
      pressure measurements in both iliac and inferior cava veins were performed in
      rats 30 days after fistula creation. Tight circumference and femoral bone length
      were measured. Histopathology and morphology of soleus muscle, extensor digitorum
      longus muscle, and the common femoral vessel were analyzed. 30 days following
      arterio-venous fistula creation, a statistically significant elevation of blood
      pressure in common iliac vein and limb overgrowth was observed. Limb enlargement
      was caused by muscle overgrowth, varicose veins formation and bone elongation.
      Arterio-venous fistula with proximal outflow limitation led to significant
      increase of femoral vein circumference and venous wall thickness. Our study
      indicates that the described rat model mimics major clinical features
      characteristic for the human Parkes Weber syndrome: presence of arterio-venous
      fistula, venous hypertension and dilatation, varicose veins formation, and the
      limb hypertrophy. We reveal that limb overgrowth is caused by bone elongation,
      muscle hypertrophy, and venous dilatation. The newly established model will
      permit detailed studies on the mechanisms underlying the disease and on the
      efficacy of novel therapeutic strategies for the Parkes Weber syndrome treatment.

PMID- 26217942
TI  - Ewes Direct Most Maternal Attention towards Lambs that Show the Greatest Pain
      Related Behavioural Responses.
AB  - Although neonatal farm animals are frequently subjected to painful management
      procedures, the role of maternal behaviour in pain coping, has not been much
      studied. We investigated whether ewes were able to distinguish between lambs in
      pain and those that were not, and whether their behaviour altered depending on
      the severity of lamb pain. Eighty male lambs were allocated to one of 4 pain
      treatments within 24 hours of birth. Lambs were either handled only (C),
      bilaterally castrated with tight rubber rings (RR), as for RR but with the
      application of a Burdizzo clamp immediately proximal to the ring (Combined) or
      subjected to short scrotum castration (SSC) where the testicles were retained
      within the abdomen and only the scrotum removed. The behaviour of the ewe,
      treated lamb and untreated sibling where present (n = 54) were recorded for 30
      minutes after treatment. Castration treatment increased the expression of
      abnormal standing and lying postures, specific pain-related behaviours (head
      turning, stamping/kicking, easing quarters, tail wagging) and composite pain
      scores (P<0.001 for all). The greatest expression of pain-related behaviours was
      shown by lambs in the RR group, which were the only group to show rolling
      responses indicative of severe pain, followed by the SSC group. Ewes expressed
      more licking/sniffing responses to the RR and SSC lambs than towards the Combined
      and C lambs (P<0.05), and oriented most to RR lambs and least to C lambs
      (P<0.001). Ewes with two lambs also directed more attention towards the treated
      than the untreated lamb (P<0.001). The quantity of maternal care directed towards
      the lamb was positively correlated with the expression of active pain behaviours.
      The data demonstrate that ewes are able to discriminate between lambs in pain and
      those that are not, and that their response is increased with a greater severity
      of pain. 

PMID- 26217944
TI  - Bariatric surgery and associated adverse pregnancy outcomes among obese women.
AB  - OBJECTIVE: To evaluate whether bariatric surgery is associated with intrauterine
      growth restriction (IUGR). METHODS: We performed a population-based retrospective
      cohort study to estimate the relationship between prior bariatric surgery and
      adverse pregnancy outcomes. The data were collected from the 2012 Healthcare Cost
      and Utilization Project Nationwide Inpatient Sample (HCUP-NIS). Pregnancies in
      obese women with a prior bariatric surgery were compared to those of obese women
      without. Outcomes of interest were pre-eclampsia, IUGR, intrauterine fetal
      demise, large for gestational age, postpartum hemorrhage, failed induction of
      labor, cesarean delivery and operative vaginal delivery. Multivariable logistic
      regression analysis was used to adjust for potential confounders. RESULTS:
      186,605 obese women with singleton gestations were identified. Among these, 1585
      (0.8%) women had a prior bariatric surgery. Prior bariatric surgery was
      associated with an increased risk of IUGR (5.7% versus 2.2%, adjusted odds ratio
      2.89, 99% CI 1.55-5.39, p < 0.0001) even after adjusting for confounding factors.
      No differences were seen in our other outcomes of interest. CONCLUSION: Singleton
      gestations in obese women with a prior bariatric surgery have an increased risk
      of IUGR. It may be reasonable screen these pregnancies for the development of
      growth restriction.

PMID- 26217943
TI  - To Break or to Brake Neuronal Network Accelerated by Ammonium Ions?
AB  - PURPOSE: The aim of present study was to investigate the effects of ammonium ions
      on in vitro neuronal network activity and to search alternative methods of acute
      ammonia neurotoxicity prevention. METHODS: Rat hippocampal neuronal and
      astrocytes co-cultures in vitro, fluorescent microscopy and perforated patch
      clamp were used to monitor the changes in intracellular Ca2+- and membrane
      potential produced by ammonium ions and various modulators in the cells
      implicated in neural networks. RESULTS: Low concentrations of NH4Cl (0.1-4 mM)
      produce short temporal effects on network activity. Application of 5-8 mM NH4Cl:
      invariably transforms diverse network firing regimen to identical burst patterns,
      characterized by substantial neuronal membrane depolarization at plateau phase of
      potential and high-amplitude Ca2+-oscillations; raises frequency and average for
      period of oscillations Ca2+-level in all cells implicated in network; results in
      the appearance of group of "run out" cells with high intracellular Ca2+ and
      steadily diminished amplitudes of oscillations; increases astrocyte Ca2+
      signalling, characterized by the appearance of groups of cells with increased
      intracellular Ca2+-level and/or chaotic Ca2+-oscillations. Accelerated network
      activity may be suppressed by the blockade of NMDA or AMPA/kainate-receptors or
      by overactivation of AMPA/kainite-receptors. Ammonia still activate neuronal
      firing in the presence of GABA(A) receptors antagonist bicuculline, indicating
      that "disinhibition phenomenon" is not implicated in the mechanisms of networks
      acceleration. Network activity may also be slowed down by glycine, agonists of
      metabotropic inhibitory receptors, betaine, L-carnitine, L-arginine, etc.
      CONCLUSIONS: Obtained results demonstrate that ammonium ions accelerate neuronal
      networks firing, implicating ionotropic glutamate receptors, having preserved the
      activities of group of inhibitory ionotropic and metabotropic receptors. This may
      mean, that ammonia neurotoxicity might be prevented by the activation of various
      inhibitory receptors (i.e. by the reinforcement of negative feedback control),
      instead of application of various enzyme inhibitors and receptor antagonists
      (breaking of neural, metabolic and signaling systems).

PMID- 26217945
TI  - The Impacts of Heatwaves on Mortality Differ with Different Study Periods: A
      Multi-City Time Series Investigation.
AB  - BACKGROUND: Different locations and study periods were used in the assessment of
      the relationships between heatwaves and mortality. However, little is known about
      the comparability and consistency of the previous effect estimates in the
      literature. This study assessed the heatwave-mortality relationship using
      different study periods in the three largest Australian cities (Brisbane,
      Melbourne and Sydney). METHODS: Daily data on climatic variables and mortality
      for the three cities were obtained from relevant government agencies between 1988
      and 2011. A consistent definition of heatwaves was used for these cities. Poisson
      generalised additive model was fitted to assess the impact of heatwaves on
      mortality. RESULTS: Non-accidental and circulatory mortality significantly
      increased during heatwaves across the three cities even with different heatwave
      definitions and study periods. Using the summer data resulted in the largest
      increase in effect estimates compared to those using the warm season or the whole
      year data. CONCLUSION: The findings may have implications for developing standard
      approaches to evaluating the heatwave-mortality relationship and advancing heat
      health warning systems. It also provides an impetus to methodological advance for
      assessing climate change-related health consequences.

PMID- 26217946
TI  - Hormone therapy in women with primary ovarian insufficiency or early menopause.

PMID- 26217947
TI  - The importance of undertaking and publishing feasibility studies: the results
      from a randomized controlled pilot trial of The Pink Women's Wellness Program.

PMID- 26217949
TI  - Methylenetetrahydrofolate reductase gene polymorphisms in Egyptian Turner
      Syndrome patients.
AB  - BACKGROUND: Folate metabolism dysfunctions can result in DNA hypomethylation and
      abnormal chromosome segregation. Two common polymorphisms of the
      methylenetetrahydrofolate reductase (MTHFR) encoding gene (C677T and A1298C)
      reduce MTHFR activity, but when associated with aneuploidy, the results are
      conflicting. Turner Syndrome (TS) is an interesting model for investigating the
      association between MTHFR gene polymorphisms and nondisjunction because of the
      high frequency of chromosomal mosaicism in this syndrome. OBJECTIVE: To
      investigate the association of MTHFR gene C677T and A1298C polymorphisms in TS
      patients and their mothers and to correlate these polymorphisms with maternal
      risk of TS offspring. SUBJECTS AND METHODS: MTHFR C677T and A1298C polymorphisms
      were genotyped in 33 TS patients, their mothers and 15 healthy females with their
      mothers as controls using polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and sequencing technique. RESULTS: Genotype and allele
      frequencies of both C677T and A1298C were not significantly different between TS
      cases and controls. There were no significant differences in C677T genotype
      distribution between the TS mothers and controls (p=1). The MTHFR 1298AA and
      1298AC genotypes were significantly increased in TS mothers Vs. control mothers
      (p=0.002). The C allele frequency of the A1298C polymorphism was significantly
      different between the TS mothers and controls (p=0.02). The association of A1298C
      gene polymorphism in TS patients was found to increase with increasing age of
      both mothers (p=0.026) and fathers (p=0.044) of TS cases. CONCLUSION: Our
      findings suggest a strong association between maternal MTHFR A1298C and risk of
      TS in Egypt.

PMID- 26217948
TI  - Is PCR the Next Reference Standard for the Diagnosis of Schistosoma in Stool? A
      Comparison with Microscopy in Senegal and Kenya.
AB  - BACKGROUND: The current reference test for the detection of S. mansoni in endemic
      areas is stool microscopy based on one or more Kato-Katz stool smears. However,
      stool microscopy has several shortcomings that greatly affect the efficacy of
      current schistosomiasis control programs. A highly specific multiplex real-time
      polymerase chain reaction (PCR) targeting the Schistosoma internal transcriber
      spacer-2 sequence (ITS2) was developed by our group a few years ago, but so far
      this PCR has been applied mostly on urine samples. Here, we performed more in
      depth evaluation of the ITS2 PCR as an alternative method to standard microscopy
      for the detection and quantification of Schistosoma spp. in stool samples.
      METHODOLOGY/PRINCIPAL FINDINGS: Microscopy and PCR were performed in a Senegalese
      community (n = 197) in an area with high S. mansoni transmission and co
      occurrence of S. haematobium, and in Kenyan schoolchildren (n = 760) from an area
      with comparatively low S. mansoni transmission. Despite the differences in
      Schistosoma endemicity the PCR performed very similarly in both areas; 13-15%
      more infections were detected by PCR when comparing to microscopy of a single
      stool sample. Even when 2-3 stool samples were used for microscopy, PCR on one
      stool sample detected more infections, especially in people with light-intensity
      infections and in children from low-risk schools. The low prevalence of soil
      transmitted helminthiasis in both populations was confirmed by an additional
      multiplex PCR. CONCLUSIONS/SIGNIFICANCE: The ITS2-based PCR was more sensitive
      than standard microscopy in detecting Schistosoma spp. This would be particularly
      useful for S. mansoni detection in low transmission areas, and post-control
      settings, and as such improve schistosomiasis control programs, epidemiological
      research, and quality control of microscopy. Moreover, it can be complemented
      with other (multiplex real-time) PCRs to detect a wider range of helminths and
      thus enhance effectiveness of current integrated control and elimination
      strategies for neglected tropical diseases.

PMID- 26217950
TI  - The role of microtubules in electrotaxis of rat Walker carcinosarcoma WC256
      cells.
AB  - The endogenous electric field may provide an important signal for directional
      cell migration during cancer metastasis but the mechanism of cell electrotaxis is
      poorly understood. It was postulated that microtubules play a central role in the
      polarization and directional migration of several types of cells. In this paper
      we investigated the role of microtubules in electrotaxis of rat Walker
      carcinosarcoma WC256 cells. We found that colchicine-stimulated disassembly of
      microtubules caused the formation of blebs instead of lamellipodia at the front
      of about 45% of cells. Most of the remaining cells contracted and became rounded
      or transformed into non-polar cells. Depolymerization of microtubules in both
      subpopulations of cells reduced the directionality of cell migration to about 50%
      of the control, but bleb- forming cells migrated much more efficiently than
      lamellipodia-forming cells. The analysis of microtubules architecture in the
      presence of an endogenous electric field showed that there is no relationship
      between the direction of migration and the polarization of microtubules. These
      results suggest that microtubules are not indispensable for electrotaxis of WC256
      cells, however they may improve the directionality of cell migration. 

PMID- 26217951
TI  - Predicting Soluble Nickel in Soils Using Soil Properties and Total Nickel.
AB  - Soil soluble nickel (Ni) concentration is very important for determining soil Ni
      toxicity. In the present study, the relationships between soil properties, total
      and soluble Ni concentrations in soils were developed in a wide range of soils
      with different properties and climate characteristics. The multiple regressions
      showed that soil pH and total soil Ni concentrations were the most significant
      parameters in predicting soluble Ni concentrations with the adjusted
      determination coefficients (Radj2) values of 0.75 and 0.68 for soils spiked with
      soluble Ni salt and the spiked soils leached with artificial rainwater to mimic
      field conditions, respectively. However, when the soils were divided into three
      categories (pH < 7, 7-8 and > 8), they obtained better predictions with Radj2
      values of 0.78-0.90 and 0.79-0.94 for leached and unleached soils, respectively.
      Meanwhile, the other soil properties, such as amorphous Fe and Al oxides and
      clay, were also found to be important for determining soluble Ni concentrations,
      indicating that they were also presented as active adsorbent surfaces.
      Additionally, the whole soil speciation including bulk soil properties and total
      soils Ni concentrations were analyzed by mechanistic speciation models WHAM VI
      and Visual MINTEQ3.0. It was found that WHAM VI provided the best predictions for
      the soils with pH < 7, was relatively reasonable for pH 7 to 8, and gave an
      overestimation for pH > 8. The Visual MINTEQ3.0 could provide better estimation
      for pH < 8 and meanwhile quite reasonable results for pH > 8. These results
      indicated the possibility and applicability of these models to predict soil
      soluble Ni concentration by soil properties. 

PMID- 26217953
TI  - Correction: Human Adipose Tissue-Derived Mesenchymal Stem Cells Target Brain
      Tumor-Initiating Cells.

PMID- 26217952
TI  - Novel full-spectral flow cytometry with multiple spectrally-adjacent fluorescent
      proteins and fluorochromes and visualization of in vivo cellular movement.
AB  - Flow cytometric analysis with multicolor fluoroprobes is an essential method for
      detecting biological signatures of cells. Here, we present a new full-spectral
      flow cytometer (spectral-FCM). Unlike conventional flow cytometer, this spectral
      FCM acquires the emitted fluorescence for all probes across the full-spectrum
      from each cell with 32 channels sequential PMT unit after dispersion with prism,
      and extracts the signals of each fluoroprobe based on the spectral shape of each
      fluoroprobe using unique algorithm in high speed, high sensitive, accurate,
      automatic and real-time. The spectral-FCM detects the continuous changes in
      emission spectra from green to red of the photoconvertible protein, KikGR with
      high-spectral resolution and separates spectrally-adjacent fluoroprobes, such as
      FITC (Emission peak (Em) 519 nm) and EGFP (Em 507 nm). Moreover, the spectral-FCM
      can measure and subtract autofluorescence of each cell providing increased signal
      to-noise ratios and improved resolution of dim samples, which leads to a
      transformative technology for investigation of single cell state and function.
      These advances make it possible to perform 11-color fluorescence analysis to
      visualize movement of multilinage immune cells by using KikGR-expressing mice.
      Thus, the novel spectral flow cytometry improves the combinational use of
      spectrally-adjacent various FPs and multicolor fluorochromes in metabolically
      active cell for the investigation of not only the immune system but also other
      research and clinical fields of use.

PMID- 26217954
TI  - Correction: PCR Primers for Metazoan Nuclear 18S and 28S Ribosomal DNA Sequences.

PMID- 26217955
TI  - Chromosomal Aberrations in Wild Mice Captured in Areas Differentially
      Contaminated by the Fukushima Dai-Ichi Nuclear Power Plant Accident.
AB  - Following the Fukushima Dai-ichi Nuclear Power Plant accident, radiation effects
      on nonhuman biota in the contaminated areas have been a great concern. The
      induction of chromosomal aberrations in splenic lymphocytes of small Japanese
      field mice (Apodemus argenteus) and house mice (Mus musculus) inhabiting
      Fukushima Prefecture was investigated. In mice inhabiting the slightly
      contaminated area, the average frequency of dicentric chromosomes was similar to
      that seen in mice inhabiting a noncontaminated control area. In contrast, mice
      inhabiting the moderately and heavily contaminated areas showed a significant
      increase in the average frequencies of dicentric chromosomes. Total absorbed dose
      rate was estimated to be approximately 1 mGy d(-1) and 3 mGy d(-1) in the
      moderately and heavily contaminated areas, respectively. Chromosomal aberrations
      tended to roughly increase with dose rate. Although theoretically, the frequency
      of chromosomal aberrations was considered proportional to the absorbed dose,
      chromosomal aberrations in old mice (estimated median age 300 days) did not
      increase with radiation dose at the same rate as that observed in young mice
      (estimated median age 105 days).

PMID- 26217956
TI  - Enzymatic reaction modulated gold nanorod end-to-end self-assembly for ultrahigh
      sensitively colorimetric sensing of cholinesterase and organophosphate pesticides
      in human blood.
AB  - We present herein the first reported self-assembly modulation of gold nanorods
      (AuNRs) by enzymatic reaction, which is further employed for colorimetric assays
      of cholinesterase (ChE) and organophosphate pesticides (OPs) in human blood. ChE
      catalyzes its substrate (acetylthiocholine) and produces thiocholine and acetate
      acid. The resulting thiols then react with the tips of the AuNRs by S-Au
      conjunction and prevent subsequent cysteine-induced AuNR end-to-end (EE) self
      assembly. Correspondingly, the AuNR surface plasmon resonance is regulated, which
      results in a distinctly ratiometric signal output. Under optimal conditions, the
      linear range is 0.042 to 8.4 MUU/mL, and the detection limit is as low as 0.018
      MUU/mL. As ChE is incubated with OPs, the enzymatic activity is inhibited. So,
      the cysteine-induced assembly is observed again. On the basis of this principle,
      OPs can be well determined ranging from 0.12 to 40 pM with a 0.039 pM detection
      limit. To our knowledge, the present quasi pU/mL level sensitivity for ChE and
      the quasi femtomolar level sensitivity for OPs are at least 500 and 7000 times
      lower than those of previous colorimetric methods, respectively. The ultrahigh
      sensitivity results from (1) the rational choice of anisotropic AuNRs as building
      blocks and reporters and (2) the specific structure of the enzymatic thiocholine.
      Because of ultrahigh sensitivity, serum samples are allowed to be extremely
      diluted in the assay. Accordingly, various nonspecific interactions, even from
      glutathione/cysteine, are well avoided. So, both ChE and OPs in human blood can
      be directly assayed without any prepurification, indicating the simplicity and
      practical promise of the proposed method. 

PMID- 26217957
TI  - How to Break the Cycle of Low Workforce Diversity: A Model for Change.
AB  - Social justice concerns but also perceived business advantage are behind a
      widespread drive to increase workplace diversity. However, dominance in terms of
      ethnicity, gender or other aspects of diversity has been resistant to change in
      many sectors. The different factors which contribute to low diversity are often
      hotly contested and difficult to untangle. We propose that many of the barriers
      to change arise from self-reinforcing feedbacks between low group diversity and
      inclusivity. Using a dynamic model, we demonstrate how bias in employee
      appointment and departure can trap organizations in a state with much lower
      diversity than the applicant pool: a workforce diversity "poverty trap". Our
      results also illustrate that if turnover rate is low, employee diversity takes a
      very long time to change, even in the absence of any bias. The predicted rate of
      change in workforce composition depends on the rate at which employees enter and
      leave the organization, and on three measures of inclusion: applicant diversity,
      appointment bias and departure bias. Quantifying these three inclusion measures
      is the basis of a new, practical framework to identify barriers and opportunities
      to increasing workforce diversity. Because we used a systems approach to
      investigate underlying feedback mechanisms rather than context-specific causes of
      low workforce diversity, our results are applicable across a wide range of
      settings. 

PMID- 26217958
TI  - Pathway Relevance Ranking for Tumor Samples through Network-Based Data
      Integration.
AB  - The study of cancer, a highly heterogeneous disease with different causes and
      clinical outcomes, requires a multi-angle approach and the collection of large
      multi-omics datasets that, ideally, should be analyzed simultaneously. We present
      a new pathway relevance ranking method that is able to prioritize pathways
      according to the information contained in any combination of tumor related omics
      datasets. Key to the method is the conversion of all available data into a single
      comprehensive network representation containing not only genes but also
      individual patient samples. Additionally, all data are linked through a network
      of previously identified molecular interactions. We demonstrate the performance
      of the new method by applying it to breast and ovarian cancer datasets from The
      Cancer Genome Atlas. By integrating gene expression, copy number, mutation and
      methylation data, the method's potential to identify key pathways involved in
      breast cancer development shared by different molecular subtypes is illustrated.
      Interestingly, certain pathways were ranked equally important for different
      subtypes, even when the underlying (epi)-genetic disturbances were diverse. Next
      to prioritizing universally high-scoring pathways, the pathway ranking method was
      able to identify subtype-specific pathways. Often the score of a pathway could
      not be motivated by a single mutation, copy number or methylation alteration, but
      rather by a combination of genetic and epi-genetic disturbances, stressing the
      need for a network-based data integration approach. The analysis of ovarian
      tumors, as a function of survival-based subtypes, demonstrated the method's
      ability to correctly identify key pathways, irrespective of tumor subtype. A
      differential analysis of survival-based subtypes revealed several pathways with
      higher importance for the bad-outcome patient group than for the good-outcome
      patient group. Many of the pathways exhibiting higher importance for the bad
      outcome patient group could be related to ovarian tumor proliferation and
      survival. 

PMID- 26217961
TI  - Mesolysis Mechanisms of Aromatic Thioether Radical Anions Studied by Pulse
      Radiolysis and DFT Calculations.
AB  - The mesolysis mechanisms for eight aromatic thioether radical anions (ArCH2SAr'(*
      )) generated during radiolysis in 2-methyltetrahydrofuran were studied by
      spectroscopic measurements and DFT calculation. Seven of ArCH2SAr'(*-) underwent
      mesolysis via dissociation of the sigma-bond between the benzylic carbon and
      sulfur atoms, forming the corresponding radical and anion with the stepwise
      mechanism or concerted mechanism. Conversely, no mesolysis in the benzyl beta
      naphthyl sulfide radical anion was found. From the Arrhenius analysis of the
      mesolysis with the stepwise mechanism, apparent activation energies (DeltaEexp)
      were determined and compared with those (DeltaEcal) estimated by the DFT
      calculations. Two types of C-S bond dissociation are possible to give the C
      radical and S anion (ArCH2(*)/Ar'S(-)) and the C anion and S radical (ArCH2(
      )/Ar'S(*)). The dissociation energies (BDE(ArCH2(*)/Ar'S(-)) and BDE(ArCH2(
      )/Ar'S(*))) were estimated by the DFT calculations, and BDE(ArCH2(*)/Ar'S(-))
      were found to be smaller than BDE(ArCH2(-)/Ar'S(*)). The formation of
      ArCH2(*)/Ar'S(-) was observed on the mesolysis of five ArCH2SAr'(*-), while one
      ArCH2SAr'(*-) provided ArCH2(-)/Ar'S(*). Chemical properties governing the
      mesolysis mechanisms of ArCH2SAr'(*-) are discussed. 

PMID- 26217959
TI  - Efficient PRNP deletion in bovine genome using gene-editing technologies in
      bovine cells.
AB  - Even though prion (encoded by the PRNP gene) diseases like bovine spongiform
      encephalopathy (BSE) are fatal neurodegenerative diseases in cattle, their study
      via gene deletion has been limited due to the absence of cell lines or mutant
      models. In this study, we aim to develop an immortalized fibroblast cell line in
      which genome-engineering technology can be readily applied to create gene
      modified clones for studies. To this end, this study is designed to 1)
      investigate the induction of primary fibroblasts to immortalization by
      introducing Bmi-1 and hTert genes; 2) investigate the disruption of the PRNP in
      those cells; and 3) evaluate the gene expression and embryonic development using
      knockout (KO) cell lines. Primary cells from a male neonate were immortalized
      with Bmi-1and hTert. Immortalized cells were cultured for more than 180 days
      without any changes in their doubling time and morphology. Furthermore, to
      knockout the PRNP gene, plasmids that encode transcription activator-like
      effector nuclease (TALEN) pairs were transfected into the cells, and transfected
      single cells were propagated. Mutated clonal cell lines were confirmed by T7
      endonuclease I assay and sequencing. Four knockout cell lines were used for
      somatic cell nuclear transfer (SCNT), and the resulting embryos were developed to
      the blastocyst stage. The genes (CSNK2A1, FAM64A, MPG and PRND) were affected
      after PRNP disruption in immortalized cells. In conclusion, we established
      immortalized cattle fibroblasts using Bmi-1 and hTert genes, and used TALENs to
      knockout the PRNP gene in these immortalized cells. The efficient PRNP KO is
      expected to be a useful technology to develop our understanding of in vitro prion
      protein functions in cattle. 

PMID- 26217962
TI  - Incidence of preeclampsia in pregnant Swiss women.
AB  - QUESTION UNDER STUDY: The epidemiology of preeclampsia in Switzerland is known
      only from a retrospective registry study. This analysis aimed to prospectively
      determine the incidence of preeclampsia in a cohort of pregnant women in
      Switzerland. METHODS: Pregnant women presenting at gestational week 11-14 at
      their obstetrician's office were consecutively included and prospectively
      followed-up until the end of pregnancy. Ultrasound characteristics, blood
      pressure measurements, body mass index, and personal history were recorded.
      Duration of pregnancy, occurrence of preeclampsia, birth weight and Apgar scores
      were recorded as outcomes. RESULTS: There were 1,300 pregnancies with follow-up
      available for analysis. Median age was 30 years (interquartile range [IQR] 27
      33), median body mass index (BMI) 23.3 kg/m2 (IQR 21.2-26.1), median systolic
      blood pressure 117 mm Hg (IQR 109-126) and median diastolic blood pressure 70 mm
      Hg (IQR 64-77). A total of 30 women developed preeclampsia, corresponding to an
      incidence of 2.31% (95% confidence interval [CI] 1.62%-3.28%). Of the women with
      preeclampsia, 6.66% (95% CI 2.04%-21.42%) had early-onset preeclampsia, 13.33%
      (95% CI 5.45%-29.83%) progressed to eclampsia, whereas 10% (95% CI 3.63%-28.75%)
      developed HELLP syndrome (haemolysis, elevated liver enzymes, low platelet
      count). Nulliparity and prior history of preeclampsia were more frequently seen
      in pregnancies with preeclampsia than in pregnancies without preeclampsia. BMI,
      as well as systolic and diastolic blood pressure were higher in pregnancies
      subsequently developing preeclampsia. CONCLUSION: The incidence of preeclampsia
      in Switzerland is in line with frequencies observed elsewhere in the world.
      Extrapolation to a national level indicates that about 1,911 (range 1,340-2,713)
      preeclampsia cases per year can be expected to occur in Switzerland.

PMID- 26217963
TI  - Robust detection of heart beats in multimodal records using slope- and peak
      sensitive band-pass filters.
AB  - In this work, we present the development, architecture and evaluation of a new
      and robust heart beat detector in multimodal records. The detector uses
      electrocardiogram (ECG) signals, and/or pulsatile (P) signals, such as: blood
      pressure, artery blood pressure and pulmonary artery pressure, if present. The
      base approach behind the architecture of the detector is collecting signal energy
      (differentiating and low-pass filtering, squaring, integrating). To calculate the
      detection and noise functions, simple and fast slope- and peak-sensitive band
      pass digital filters were designed. By using morphological smoothing, the
      detection functions were further improved and noise intervals were estimated. The
      detector looks for possible pacemaker heart rate patterns and repairs the ECG
      signals and detection functions. Heart beats are detected in each of the ECG and
      P signals in two steps: a repetitive learning phase and a follow-up detecting
      phase. The detected heart beat positions from the ECG signals are merged into a
      single stream of detected ECG heart beat positions. The merged ECG heart beat
      positions and detected heart beat positions from the P signals are verified for
      their regularity regarding the expected heart rate. The detected heart beat
      positions of a P signal with the best match to the merged ECG heart beat
      positions are selected for mapping into the noise and no-signal intervals of the
      record. The overall evaluation scores in terms of average sensitivity and
      positive predictive values obtained on databases that are freely available on the
      Physionet website were as follows: the MIT-BIH Arrhythmia database (99.91%), the
      MGH/MF Waveform database (95.14%), the augmented training set of the follow-up
      phase of the PhysioNet/Computing in Cardiology Challenge 2014 (97.67%), and the
      Challenge test set (93.64%). 

PMID- 26217964
TI  - Phenylalanine Blocks Defects Induced in Gel Lipid Membranes by Osmotic Stress.
AB  - We study the binding of phenylalanine (Phe) with dipalmitoylphosphocholine (DPPC)
      vesicles in gel (25  degrees C) and in liquid crystalline states (50  degrees C)
      and in gel large unilamellar vesicles (LUVs) subjected to osmotic dehydration
      with merocyanine (MC 540) as a fluorescent surface membrane marker. Phe does not
      produce significant changes in MC 540 monomer concentration in DPPC LUVs at 50 
      degrees C. In contrast, it significantly decreases the monomer adsorption in
      defects present in DPPC LUVs at 25  degrees C. When DPPC LUVs were subjected to
      hypertonic stress, dehydration caused more defects, and in this case
      phenylalanine is also able to block such defects. 

PMID- 26217965
TI  - Structural Modification of the Designer Stimulant alpha-Pyrrolidinovalerophenone
      (alpha-PVP) Influences Potency at Dopamine Transporters.
AB  - alpha-Pyrrolidinovalerophenone (alpha-PVP, 7) is an illegal synthetic stimulant
      that is being sold on the clandestine market as "flakka" and "gravel". The potent
      pharmacological effects of alpha-PVP are presumably mediated by inhibition of
      dopamine uptake at the dopamine transporter (DAT). However, little is known about
      how structural modification of alpha-PVP influences activity at DAT. Eleven
      analogs of alpha-PVP were synthesized and examined for their ability to inhibit
      uptake of [(3)H]dopamine and [(3)H]serotonin in rat brain synaptosomes. None of
      the analogs significantly inhibited [(3)H]serotonin uptake when tested at 10 MUM
      at the serotonin transporter (SERT). All of the analogs behaved as DAT reuptake
      inhibitors, but potencies varied over a >1500-fold range. Potency was primarily
      associated with the nature of the alpha-substituent, with the more bulky
      substituents imparting the highest potency. Expansion of the pyrrolidine ring to
      a piperidine reduced potency up to 10-fold, whereas conformational constraint in
      the form of an aminotetralone resulted in the least potent compound. Our study
      provides the first systematic and comparative structure-activity investigation on
      the ability of alpha-PVP analogs to act as inhibitors of DAT. 

PMID- 26217966
TI  - Stannyl-Lithium: A Facile and Efficient Synthesis Facilitating Further
      Applications.
AB  - We have developed a highly efficient, practical, polycyclic aromatic hydrocarbon
      (PAH)-catalyzed synthesis of stannyl lithium (Sn-Li), in which the tin resource
      (stannyl chloride or distannyl) is rapidly and quantitatively transformed into Sn
      Li reagent at room temperature without formation of any (toxic) byproducts. The
      resulting Sn-Li reagent can be stored at ambient temperature for months and shows
      high reactivity toward various substrates, with quantitative atom efficiency. 

PMID- 26217967
TI  - Photothermal Electrical Resonance Spectroscopy of Physisorbed Molecules on a
      Nanowire Resonator.
AB  - Mid-infrared (IR) photothermal spectroscopy of adsorbed molecules is an ideal
      technique for molecular recognition in miniature sensors with very small thermal
      mass. Here, we report on combining the photothermal spectroscopy with electrical
      resonance of a semiconductor nanowire for enhanced sensitivity, selectivity, and
      simplified readout. Wide band gap semiconductor bismuth ferrite nanowire, by
      virtue of its very low thermal mass and abundance of surface states in the band
      gap, facilitates thermally induced charge carrier trapping in the surface states,
      which affects its electrical resonance response. Electrical resonance response of
      the nanowire varies significantly depending on the photothermal spectrum of the
      adsorbed molecules. We demonstrate highly selective detection of mid-IR
      photothermal spectral signatures of femtogram level molecules physisorbed on a
      nanowire by monitoring internal dissipation response at its electrical resonance.

PMID- 26217978
TI  - Antagonism of quercetin against tremor induced by unilateral striatal lesion of 6
      OHDA in rats.
AB  - Quercetin, a flavonoid present in many plants, is reported to be effective in
      models of neurodegenerative diseases. The aim of the present study was to
      evaluate the anti-tremor effects of quercetin in 6-hydroxydopamine (6-OHDA)
      induced rat model of Parkinson's disease. In rats, quercetin had no effect on
      apomorphine-induced rotations, but it could significantly attenuate muscle tremor
      of 6-OHDA lesioned rats. Interestingly, quercetin could decrease the burst
      frequency in a dose- and time-dependent manner. These results suggest that
      quercetin may have a protective effect on models to mimic muscle tremors of
      Parkinson's disease. This effect of quercetin may be associated with serotonergic
      system, but further study is needed. 

PMID- 26217968
TI  - Pharmacological gating modulation of small- and intermediate-conductance Ca(2+)
      activated K(+) channels (KCa2.x and KCa3.1).
AB  - This short review discusses pharmacological modulation of the opening/closing
      properties (gating) of small- and intermediate-conductance Ca(2+)-activated K(+)
      channels (KCa2 and KCa3.1) with special focus on mechanisms-of-action,
      selectivity, binding sites, and therapeutic potentials. Despite KCa channel
      gating-modulation being a relatively novel field in drug discovery, efforts in
      this area have already revealed a surprising plethora of pharmacological sites-of
      actions and channel subtype selectivity exerted by different chemical classes.
      The currently published positive modulators show that such molecules are
      potentially useful for the treatment of various neurodegenerative disorders such
      as ataxia, alcohol dependence, and epilepsy as well as hypertension. The negative
      KCa2 modulators are very effective agents for atrial fibrillation. The prediction
      is that further unraveling of the molecular details of gating pharmacology will
      allow for the design of even more potent and subtype selective KCa modulators
      entering into drug development for these indications. 

PMID- 26217979
TI  - Apparent Cooling Rate of 7 degrees C per Hour in an Avalanche Victim.
AB  - Avalanche victims can become hypothermic within 35 minutes of snow burial.
      However, reported cooling rates for avalanche victims are highly variable and it
      is poorly understood how much cooling is influenced by general factors (body
      composition, clothing, ambient conditions, duration of burial, and metabolism),
      unknown inter-individual factors or other phenomena (e.g., afterdrop). We report
      an apparent cooling rate of ~7 degrees C in ~60 minutes in a healthy backcountry
      skier who was rewarmed with forced air and warm fluids and was discharged after 2
      weeks without neurological sequelae.

PMID- 26217980
TI  - Development of an Agility Test for Badminton Players and Assessment of Its
      Validity and Test-Retest Reliability.
AB  - CONTEXT: Badminton requires open and fast actions toward the shuttlecock, but
      there is no specific agility test for badminton players with specific movements.
      PURPOSE: To develop an agility test that simultaneously assesses perception and
      motor capacity and examine the test's concurrent and construct validity and its
      test-retest reliability. METHOD: The Badcamp agility test consists of running as
      fast as possible to 6 targets placed on the corners and middle points of a
      rectangular area (5.6 * 4.2 m) from the start position located in the center of
      it, following visual stimuli presented in a luminous panel. The authors recruited
      43 badminton players (17-32 y old) to evaluate concurrent (with shuttle-run
      agility test--SRAT) and construct validity and test-retest reliability. RESULTS:
      Results revealed that Badcamp presents concurrent and construct validity, as its
      performance is strongly related to SRAT (rho = 0.83, P < .001), with performance
      of experts being better than nonexpert players (P < .01). In addition, Badcamp is
      reliable, as no difference (P = .07) and a high intraclass correlation (ICC =
      .93) were found in the performance of the players on 2 different occasions.
      CONCLUSIONS: The findings indicate that Badcamp is an effective, valid, and
      reliable tool to measure agility, allowing coaches and athletic trainers to
      evaluate players' athletic condition and training effectiveness and possibly
      detect talented individuals in this sport.

PMID- 26217981
TI  - Acute kidney injury and pneumothorax are risk factors for mortality in persistent
      pulmonary hypertension of the newborn in Thai neonates.
AB  - OBJECTIVES: To describe the clinical characteristics, diagnostic methods,
      treatment modalities, and complications, and identify the mortality risk factors,
      of infants with short-term persistent pulmonary hypertension of the newborn
      (PPHN). METHODS: The clinical data of infants diagnosed with PPHN at Hat Yai
      Hospital from January 2010 to February 2014 were retrospectively reviewed. Cox
      proportional hazard regression analysis was performed to assess factors
      associated with mortality. RESULTS: The records of 119 infants were analyzed. Of
      these, 47 died giving an in-hospital mortality rate of 39.5%. The prevalence of
      PPHN (based on inborn births) was 2.8 per 1000 live births. The mean gestational
      age and birth weight were 39.1 +/- 1.6 weeks and 3044 +/- 563 g, respectively.
      Multivariate Cox regression analysis indicated that pneumothorax [adjusted hazard
      ratio (HR) = 2.07 (95% CI 1.09-3.93)] and acute kidney injury [adjusted HR = 2.99
      (95% CI 1.59-5.61)] were factors associated independently with an increased risk
      for death, while infants who received total parenteral nutrition [adjusted HR =
      0.22 (95% CI 0.10-0.50)] had lower mortality. CONCLUSION: A high mortality rate
      of PPHN was observed in this study. Significantly higher mortality was noted in
      infants complicated with pneumothorax and acute kidney injury.

PMID- 26217984
TI  - Diffusion-weighted magnetic resonance imaging during radiotherapy of locally
      advanced cervical cancer--treatment response assessment using different
      segmentation methods.
AB  - BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) and the
      derived apparent diffusion coefficient (ADC) value has potential for monitoring
      tumor response to radiotherapy (RT). Method used for segmentation of volumes with
      reduced diffusion will influence both volume size and observed distribution of
      ADC values. This study evaluates: 1) different segmentation methods; and 2) how
      they affect assessment of tumor ADC value during RT. MATERIAL AND METHODS: Eleven
      patients with locally advanced cervical cancer underwent MRI three times during
      their RT: prior to start of RT (PRERT), two weeks into external beam RT (WK2RT)
      and one week prior to brachytherapy (PREBT). Volumes on DW-MRI were segmented
      using three semi-automatic segmentation methods: "cluster analysis", "relative
      signal intensity (SD4)" and "region growing". Segmented volumes were compared to
      the gross tumor volume (GTV) identified on T2-weighted MR images using the
      Jaccard similarity index (JSI). ADC values from segmented volumes were compared
      and changes of ADC values during therapy were evaluated. RESULTS: Significant
      difference between the four volumes (GTV, DWIcluster, DWISD4 and DWIregion) was
      found (p < 0.01), and the volumes changed significantly during treatment (p <
      0.01). There was a significant difference in JSI among segmentation methods at
      time of PRERT (p < 0.016) with region growing having the lowest JSIGTV (mean+/-
      sd: 0.35 +/- 0.1), followed by the SD4 method (mean+/- sd: 0.50 +/- 0.1) and
      clustering (mean+/- sd: 0.52 +/- 0.3). There was no significant difference in
      mean ADC value compared at same treatment time. Mean tumor ADC value increased
      significantly (p < 0.01) for all methods across treatment time. CONCLUSION: Among
      the three semi-automatic segmentations of hyper-intense intensities on DW-MR
      images implemented, cluster analysis and relative signal thresholding had the
      greatest similarity to the clinical tumor volume. Evaluation of mean ADC value
      did not depend on segmentation method.

PMID- 26217985
TI  - Incidence of cancer among grand multiparous women in Finland with special focus
      on non-gynaecological cancers: A population-based cohort study.
AB  - BACKGROUND: Many studies have previously revealed evidence of an association
      between grand multiparity (five or more deliveries) and gynaecological cancer.
      Oestrogen has an impact on cancer formation and the amount of circulating
      oestrogen is significantly higher during pregnancy. Also the lifestyle of grand
      multiparous women differs somewhat from the average population. Considering these
      factors it is plausible that also non-gynaecological cancers are associated with
      multiparity. The aim of our study was to determine cancer incidence among grand
      multiparous women, with special attention to non-gynaecological cancers. MATERIAL
      AND METHODS: All 102 541 women alive in 1974-2011 and having had at least five
      deliveries were identified in the Finnish Population Register and followed up for
      cancer incidence through the Finnish Cancer Registry to the end of 2011.
      Standardised incidence ratios (SIRs) were defined as ratios between observed and
      expected numbers of cases, the latter ones based on incidence in the entire
      Finnish female population. RESULTS: The overall incidence of non-gynaecological
      cancers was the same as in the reference population (SIR 0.98, 95% confidence
      interval 0.90-1.06). The incidence of cancers of the gall-bladder (SIR 1.42, 1.26
      1.58), biliary tract (1.19, 1.04-1.35) and kidney (1.22, 1.14-1.31) was
      increased. There were significantly fewer cases than expected of urinary bladder
      cancer (SIR 0.70, 0.61-0.78), lung cancer (0.87, 0.81-0.92), colon cancer (0.94,
      0.89-0.99) and all types of skin cancers. As a consequence of the decreased
      incidence of gynaecological cancers (SIR 0.74, 0.71-0.77) and breast cancer
      (0.60, 0.58-0.61), the SIR for cancer overall was 0.84 (0.83-0.85). CONCLUSION:
      The study demonstrated that grand multiparous women have a similar overall risk
      of non-gynaecological cancers as other women, despite significant differences in
      some specific forms of cancer.

PMID- 26217986
TI  - Optimal fractionation in radiotherapy for non-small cell lung cancer--a modelling
      approach.
AB  - BACKGROUND: Conventionally fractionated radiotherapy (CFRT) has proven
      ineffective in treating non-small cell lung cancer while more promising results
      have been obtained with stereotactic body radiotherapy (SBRT). Hypoxic tumours,
      however, might present a challenge to extremely hypofractionated schedules due to
      the decreased possibility for inter-fraction fast reoxygenation. A potentially
      successful compromise might be found in schedules employing several fractions of
      varying fractional doses. In this modelling study, a wide range of fractionation
      schedules from single-fraction treatments to heterogeneous, multifraction
      schedules taking into account repair, repopulation, reoxygenation and
      radiosensitivity of the tumour cells, has been explored with respect to the
      probability of controlling lung tumours. MATERIAL AND METHODS: The response to
      radiation of tumours with heterogeneous spatial and temporal oxygenation was
      simulated including the effects of accelerated repopulation and intra-fraction
      repair. Various treatments with respect to time, dose and fractionation were
      considered and the outcome was estimated as Poisson-based tumour control
      probability for local control. RESULTS: For well oxygenated tumours,
      heterogeneous fractionation could increase local control while hypoxic tumours
      are not efficiently targeted by such treatments despite reoxygenation. For
      hypofractionated treatments employing large doses per fraction, a synergistic
      effect was observed between intra-fraction repair and inter-fraction fast
      reoxygenation of the hypoxic cells as demonstrated by a reduction in D50 from
      53.3 Gy for 2 fractions to 52.7 Gy for 5 fractions. CONCLUSIONS: For well
      oxygenated tumours, heterogeneous fractionation schedules could increase local
      control rates substantially compared to CFRT. For hypoxic tumours, SBRT-like
      hypofractionated schedules might be optimal despite the increased risk of intra
      fraction repair due to a synergistic effect with inter-fraction reoxygenation.

PMID- 26217987
TI  - Variability of dynamic 18F-FDG-PET data in breast cancer xenografts.
AB  - BACKGROUND: A murine breast cancer xenograft model was employed to evaluate inter
      and intra-variability of various parameters derived from dynamic positron
      emission tomography with [18F]-fluorodeoxyglucose as tracer (FDG-PET). MATERIAL
      AND METHODS: Seventeen female athymic nude foxn1/nu mice with bilaterally
      implanted triple-negative basal-like ductal carcinoma (MAS98.12) breast cancer
      xenografts underwent a dynamic PET scan over an hour after injection of
      approximately 10 MBq FDG. Inter-animal data were obtained from the entire animal
      cohort, while intra-animal data were from four mice receiving an additional scan
      after one or two days. Standardised uptake values (SUVmax, SUVmean and SUVmedian)
      were estimated for all tumours at different time points. Tumour uptake was
      analysed with a kinetic two-compartment model for estimation of pharmacokinetic
      parameters. The coefficient of variation (CV) was calculated for all PET-derived
      metrics. RESULTS: The CVs for SUVmean and SUVmedian were typically 10-20% for the
      tumours, depending on the time post-injection and group (intra vs. inter). The CV
      for SUVmax was mostly higher. The variability in the pharmacokinetic parameters
      ranged from 23 to almost 150%. CONCLUSIONS: SUVmean and SUVmedian show less
      variability than SUVmax. The pharmacokinetic tumour metrics again display much
      greater variability than the SUV-based metrics. However, it is generally not
      known which of these metrics that best represents cancer aggressiveness and their
      use may still depend on the research questions addressed.

PMID- 26217988
TI  - Cardiac monitoring during adjuvant trastuzumab therapy: Guideline adherence in
      clinical practice.
AB  - BACKGROUND: Cardiotoxicity is an important adverse effect of adjuvant breast
      cancer treatment with trastuzumab and three monthly left ventricular ejection
      fraction (LVEF) monitoring is considered mandatory. The purpose of this study was
      to gain insight into LVEF monitoring during adjuvant trastuzumab treatment in
      clinical practice. MATERIAL AND METHODS: In a multicenter retrospective study
      encompassing 328 patients, of which 171 patients were actually treated with
      trastuzumab, we analyzed the frequency and mode of LVEF monitoring and compared
      it with LVEF monitoring guidelines. RESULTS: The results indicated poor guideline
      adherence. In 9% of patients trastuzumab was started in spite of a low LVEF (<
      55%). In 24% of patients no valid baseline LVEF value was available. LVEF
      measurements during treatment at three, six and 12 months were only performed in,
      respectively, 53%, 40% and 30% of patients. CONCLUSION: A significant proportion
      of patients are treated with trastuzumab, while LVEF monitoring is not adequately
      performed. More attention should be paid to the implementation of (cardiac
      assessment) guidelines in clinical practice.

PMID- 26217990
TI  - The Manager's Greatest Source of Power.

PMID- 26217989
TI  - Double-Shell Architectures of ZnFe2O4 Nanosheets on ZnO Hollow Spheres for High
      Performance Gas Sensors.
AB  - In this study, double-shell composites consisting of inner ZnO hollow
      microspheres (ZHS) surrounded by outer ZnFe2O4 nanosheets were successfully
      synthesized. The growth of the ultrathin ZnFe2O4 nanosheets (~10 nm) on the ZHS
      outer surface was carried out at room temperature via solution reactions in order
      to generate a double-shell configuration that could provide a large surface area.
      As a proof-of-concept demonstration of the design, a comparative sensing
      investigation between the sensors based on the as-obtained ZnO/ZnFe2O4 composites
      and its two individual components (ZnO hollow spheres and ZnFe2O4 nanosheets) was
      performed. As expected, the response of the ZnFe2O4-decorated ZnO composites to
      100 ppm acetone was about 3 times higher than that of initial ZnO microspheres.
      Moreover, a dramatic reduction of response/recover time has been achieved at
      different operating temperature. Such favorable sensing performances endow these
      ZnO/ZnFe2O4 heterostructures with a potential application in gas sensing. 

PMID- 26217991
TI  - Workforce and Leader Development: Learning From the Baldrige Winners in Health
      Care.
AB  - It is ironic that perhaps the only constant in health care organizations today is
      change. To compete successfully in health care and position an organization for
      high performance amid continuous change, it is very important for managers to
      have knowledge of the best learning and development practices of high-performing
      organizations in their industry. The rapid increases in the rate of technological
      change and geometric increases in knowledge make it virtually imperative that
      human resources are developed effectively. This article discusses the best
      learning and development practices among the Malcolm Baldrige National Quality
      Award winners in the health care industry since 2002 when the industry had its
      first award-winning organization. 

PMID- 26217992
TI  - Health Care Finance Executive Personalities Revisited: A 10-Year Follow-up Study.
AB  - A dynamic health care industry continues to call upon health care leaders to
      possess not one but multiple competencies. Inherent personality characteristics
      of leaders often play a major role in personal as well as organizational success
      to include those in health care finance positions of responsibility. A
      replication study was conducted to determine the Myers-Briggs personality-type
      differences between practicing health care finance professionals in 2014, as
      compared with a previous 2003 study. Results indicate a significant shift between
      both independent samples of health care finance professionals over the 10-year
      period from original high levels of introversion to that of extraversion, as well
      as higher sensing personality preferences, as compared with the original sample's
      high level of intuition preferences. Further investigation into the evolving role
      of the health care finance manager is suggested, while continued alignment of
      inherent, personal characteristics is suggested to meet ongoing changes in the
      industry. 

PMID- 26217993
TI  - Implementation of Measures to Improve SCIP Perioperative Beta-Blocker Compliance:
      Quality and Financial Implications.
AB  - INTRODUCTION: The Surgical Care Improvement Project (SCIP) was launched in 2005.
      One of the SCIP metrics includes perioperative beta-blocker guideline (CARD-2),
      which measures the percentage of patients on a pre-operative beta-blocker with
      continued use in the perioperative period. Compliance is intended to decrease
      rates of acute myocardial infarction (AMI) and cardiac mortality among high-risk
      patients. We desired to create low cost, standardized processes on an
      institutional level to improve compliance with the SCIP CARD-2 metric. METHODS:
      We assessed the impact of interventions on provider compliance with the SCIP CARD
      2 metric and on simulated impact on institutional cost. RESULTS: We were able to
      improve CARD-2 compliance at one hospital within a year of intervention
      implementation. The hospital decreased its losses due to noncompliance in FY 2014
      by $27 273. DISCUSSION: A relatively low cost intervention, aimed at educating
      providers that utilized existing infrastructure resulted in improved SCIP beta
      blocker compliance. Changes in the reimbursement system made at the time of
      publication demonstrate that reimbursement measures are constantly in flux;
      tailored interventions based upon our successes may still produce similar
      results.

PMID- 26217994
TI  - Interventions of an Academic Medical Center to Improve Likelihood to Recommend.
AB  - Improved patient satisfaction is correlated with improved adherence and health
      outcomes for patients and financial performance for health care organizations.
      Increasingly, efforts are being made to measure and optimize patient satisfaction
      by both providers and insurers. Researchers investigated whether specific changes
      in staff interaction with patients would improve patients' likelihood to
      recommend a practice. There were 4 separate initiatives implemented by the
      medical staff and providers at 14 unique practice sites. At these sites,
      patients' satisfaction was measured 9 weeks prior to the initiative and then for
      9 weeks after to assess impact on patients' likelihood to recommend the practice.
      Each of the 4 initiatives demonstrated improved patient satisfaction, whereas 2
      reached statistical significance. These interventions demonstrated a rise in
      likelihood to recommend the practice score from 78.6% (33rd percentile) to 83.1%
      (68th percentile) in all of the combined practices. 

PMID- 26217995
TI  - Tweeting and Treating: How Hospitals Use Twitter to Improve Care.
AB  - Hospitals that have adopted Twitter primarily use it to share organizational
      news, provide general health care information, advertise upcoming community
      events, and foster networking. The purpose of this study was to explore the
      benefits that Twitter utilization has had in improving quality of care, access to
      care, patient satisfaction, and community footprint while assessing the barriers
      to its implementation. The methodology used was a qualitative study with a
      semistructured interview combined with a literature review, which followed the
      basic principles of a systematic review. The utilization of Twitter by hospitals
      suggest that it leads to savings of resources, enhanced employee and patient
      communication, and expanded patient reach in the community. Savings opportunities
      are generated by preventing unnecessary office visits, producing billable patient
      encounters, and eliminating high recruiting costs. Communication is enhanced
      using Twitter by sharing organizational content, news, and health promotions and
      can be also a useful tool during crises. The utilization of Twitter in the
      hospital setting has been more beneficial than detrimental in its ability to
      generate opportunities for cost savings, recruiting, communication with employees
      and patients, and community reach. 

PMID- 26217997
TI  - A Single-Center Multidisciplinary Initiative to Reduce Catheter-Associated
      Urinary Tract Infection Rates: Quality and Financial Implications.
AB  - INTRODUCTION: Catheter-associated urinary tract infection (CAUTI) is an important
      patient safety issue that is responsible for an estimated 449334 annual
      infections, with an average direct cost of $790-$1200 per infection. In total,
      the cost associated with CAUTI is estimated to be $115 million to $1.82 billion
      annually. METHODS: We conducted an internal revenue analysis with a standard
      sensitivity analysis to assess the impact of a low-cost CAUTI reduction program
      on direct costs to the hospital over four years. The interventions included the
      formation of a multidisciplinary CAUTI reduction task force, formal data
      collection in all ICUs, staff education, and new electronic order sets with
      decision support. RESULTS: During the initial intervention period, the infection
      rate per 1000 catheter days decreased from 5.4 to 1.5. In the second year of the
      program, the infection rate increased to 4.6. After additional interventions were
      launched, infection rates decreased to 2.2. Cost savings per 1000 catheter days
      (+/-20%) during the initial intervention were $4501 ($3600-$5401). DISCUSSION:
      Our intervention demonstrated that provider education and electronic
      documentation prompts were followed by a significant decrease in catheter
      utilization, that in turn was followed by lower infection rates. Decreased
      emphasis on intervention goals were followed by an increase in CAUTI rates. Our
      subsequent interventions suggest that upward trends may be reversible.

PMID- 26217998
TI  - Social Media in Health Care: How Close Is Too Close?
AB  - Social media use is increasing personally and professionally across numerous
      industries worldwide. The purpose of this article is to explore the utilization
      of social media in the health care field; specifically, how the treatment of a
      physician's Facebook friends would differ from that of a patient the physician
      did not know prior to treatment. While there are several benefits that come with
      incorporating social media into health care, as well as into the physician
      patient relationship, there are also immense risks. The present study surveyed
      physicians to assess their opinions on the boundaries of an appropriate patient
      physician relationship on social media. Fifty-six of 70 physicians responded with
      their attitudes on the difference between adding a patient as a friend and adding
      a friend as a patient, as well as the difference in care between the two. The
      results of the study showed that most physicians would not be opposed to taking
      on their Facebook friends as patients; however, the care they provide could
      potentially be radically different between their Facebook friend and an average
      patient. This means that patients should take extra care before asking their
      Facebook physician friends for formal care when they are in need. 

PMID- 26217999
TI  - Exploring Social Quality and Community Health Outcomes: An Ecological Model.
AB  - Quality of life is widely used as a measure of individual well-being in developed
      countries. Social quality (SQ), however, describes how favorable the
      socioenvironmental components are that impact the life chance of an individual.
      Despite the associations between SQ, including institutional capacity and citizen
      capacity, and other community indicators, the impact of SQ on community health
      status has not been fully examined. This study investigated the
      interrelationships among institutional capacity, citizen capacity, and their
      associations with community-level health indicators such as mortality and suicide
      among 230 local governments in South Korea. Under the principles of conceptual
      suitability, clarity, reliability, consistency, changeability, and comparability,
      a total of 81 SQ indicators were collected, and 19 indicators of the 81
      indicators were selected. The 19 indicators were transformed by the imputation of
      missing values, standardization, and geographic information system
      transformation. It was found that the health outcome of local government was
      superior as social welfare, political participation, and education were higher.
      According to the result of the regression analysis based on the regional type,
      social welfare had the most influence on the health level of local government in
      both metropolises and small-/medium-sized cities. In addition, education and
      political participation had a positive effect on the health indicator of local
      metropolis government. However, SQ indicators did not have any meaningful
      influence at the county level. Therefore, small- and medium-sized cities need to
      promote the collective health of the local government through improving social
      welfare, and metropolises need to consider the complex relationship among other
      indicators while increasing the level of social welfare and education. Meanwhile,
      counties need to develop health indicators that reflect aged population
      characteristics and social environment of rural areas. Therefore, fundamental
      social welfare benefits need to be guaranteed while improving SQ capacities in
      order to improve the health status of local governments. 

PMID- 26218000
TI  - Professional Quality of Life of Veterans Affairs Staff and Providers in a Patient
      Centered Care Environment.
AB  - Changes to the work environment prompted by the movement toward patient-centered
      care have the potential to improve occupational stress among health care workers
      by improving team-based work activities, collaboration, and employee-driven
      quality improvement. This study was conducted to examine professional quality of
      life among providers at patient-centered care pilot facilities. Surveys were
      conducted with 76 Veterans Affairs employees/providers at facilities piloting
      patient-centered care interventions, to assess demographics, workplace practices
      and views (team-based environment, employee voice, quality of communication, and
      turnover intention), and professional quality of life (compassion satisfaction,
      burnout, and secondary traumatic stress).Professional quality-of-life subscales
      were not related to employee position type, age, or gender. Employee voice
      measures were related to lower burnout and higher compassion satisfaction. In
      addition, employees who were considering leaving their position showed higher
      burnout and lower compassion satisfaction scores. None of the work practices
      showed relationships with secondary traumatic stress. 

PMID- 26218001
TI  - Participation of Rural Health Care Providers in Accountable Care Organizations:
      Early Indications.
AB  - Recently, some rural health clinics (RHCs) throughout the country have chosen to
      join groups of health care providers in accountable care organizations (ACOs).
      Examined are characteristics of Southeastern RHCs and the counties they serve; it
      is shown how those characteristics compare with other regions across the country
      and suggested what role those differences might play in an RHC's decision to
      participate in an ACO. Rural health clinic-related data were collected and
      summarized for 2 time periods: 2007 and 2011: for 2007, data from RHCs throughout
      the United States; for 2011, summarized demographic data related to region 4 RHCs
      specifically. Several characteristics about region 4 RHCs indicate that they may
      be slow to participate in ACOs. However, other characteristics, including their
      perception that ACOs may improve the quality of care and health outcomes of their
      patients and communities, may facilitate the process of RHCs joining ACOs, should
      they choose to do so. Addressing the health care needs and health care quality of
      rural populations must be part of the design, development, and performance
      monitoring of ACOs of the future. 

PMID- 26218002
TI  - The Effects of Supervisors' Support and Mediating Factors on the Nurses' Job
      Performance Using Structural Equation Modeling: A Case Study.
AB  - Nurses are the largest group and an important part of the providers in the health
      care systems that who a key role in hospitals. Any defect and deficiency in their
      work can result in irreversible outcomes. This study aimed to determine the
      effect of supervisors' support and mediating factors on the job performance
      (JOBPER) of 400 nurses working in the teaching hospitals affiliated to Shiraz
      University of Medical Sciences, using structural equation modeling. The results
      showed that the supervisor's support had a significant negative effect on work
      family conflict (t = -2.57) and a positive effect on organizational commitment (t
      = 4.03); Work-family conflict had a significant positive effect on job stress (t
      = 11.24) and a negative effect on organizational commitment (t = -3.35) and
      JOBPER (t = -2.29). Family-work conflict had a positive effect on job stress (t =
      4.48) and a negative effect on organizational commitment (t = -2.54). Finally,
      job stress had a negative effect (t = -3.30), and organizational commitment
      showed a positive effect (t = 5.96) on the studied nurses' JOBPER. According to
      the results, supervisor's support could influence JOBPER through reducing work
      family conflict and increasing organizational commitment. Therefore, to improve
      the nurses' JOBPER in the hospitals, some strategies are recommended. 

PMID- 26218003
TI  - Reducing the Burden of Pain From Vaccination: Updated Recommendations for All Age
      Groups.

PMID- 26218004
TI  - Sleep Quality Among People Living With Chronic Noncancer Pain: Findings From the
      Pain and Opioids IN Treatment (POINT) Cohort.
AB  - STUDY OBJECTIVES: To examine sleep disturbances in the POINT cohort study
      consisting of participants prescribed long-term opioids for chronic noncancer
      pain (CNCP), and to examine the relationship between sleep and measures of pain,
      physical and mental health, substance use, and medication use at the baseline
      interview. METHODS: A convenience sample of 1243 participants with current CNCP
      and prescription opioid use were recruited from community settings and underwent
      a structured interview examining subjective sleep symptoms (Medical Outcomes
      Study [MOS] Sleep Scale and the Sleep Problems Index [SLP-9]), the pain severity
      and interference using the Brief Pain Inventory (BPI), mental and physical health
      symptoms, and recent substance and medication use. Linear regression models
      assessed independent predictors of SLP-9 scores. RESULTS: The median hours of
      sleep per night was 6 (IQR, 5 to 7.5), with 26% reporting optimal sleep (7 to 8
      hours), and a mean SLP-9 score of 47.3 (SD=20.9). In multivariate analysis, age,
      frequent/severe headaches, BPI pain severity and pain interference scores,
      moderate to severe anxiety or depression, daily tobacco use, and benzodiazepine
      use in the past week were significant predictors of SLP-9 scores and sleep
      quality. Higher MOS respiratory impairment was observed in men, in those with a
      high body mass index, frequent/severe headaches, and high pain interference
      scores, and in patients taking anticonvulsants and antipsychotic medications.
      Opioid use was not associated with SLP-9 or respiratory sleep impairment.
      CONCLUSIONS: High levels of sleep problems were reported in this community sample
      of CNCP patients prescribed long-term opioids, and were associated with mental
      health problems and increased medication use. Nonmedication approaches to
      addressing sleep problems should be prioritized in this population.

PMID- 26218005
TI  - Is the Efficacy of Milnacipran in Fibromyalgia Predictable? A Data-Mining
      Analysis of Baseline and Outcome Variables.
AB  - OBJECTIVES: Minalcipran has been approved for the treatment of fibromyalgia in
      several countries including Australia. Australian agency considered that the
      overall efficacy is moderate, although clinically significant, and could be
      translated into a real and strong improvement in some patients. The determination
      of the characteristics of patients who could benefit the most from milnacipran
      (MLN) is the primary objective of this manuscript. MATERIALS AND METHODS: Data
      from the 3 pivotal phase 3 clinical trials of the Australian submission dossier
      were assembled into a database. A clustering method was implemented to exhibit
      natural groupings of homogeneous observations into clusters of efficacy outcomes
      and individual patients. Next, baseline characteristics were investigated using a
      data-mining method to determine the clinical features that may be predictive of a
      substantially improved effect of MLN on a set of efficacy outcomes. RESULTS: The
      clustering analysis reveals 3 symptom domains: "Pain and global," "Mood and
      central status," and "Function." We show that improvement in "Fatigue" goes with
      improvement in "Function." Furthermore, the predictive data-mining analysis
      exhibits 4 single baseline characteristics that are associated with a
      substantially improved effect of MLN on efficacy outcomes. These are high pain
      intensity, low anxiety or catastrophizing level, absence of major sleeping
      problems, and physical limitations in the daily life effort. DISCUSSION:
      Clustering and predictive data-mining methods provide additional insight about
      fibromyalgia, its symptoms, and treatment. The information is useful to
      physicians to optimize prescriptions in the daily practice and to regulatory
      bodies to refine indications.

PMID- 26218006
TI  - Dietary Rosa mosqueta (Rosa rubiginosa) oil prevents high diet-induced hepatic
      steatosis in mice.
AB  - The effects of dietary Rosa mosqueta (RM, Rosa rubiginosa) oil, rich in alpha
      linolenic acid, in the prevention of liver steatosis were studied in mice fed a
      high fat diet (HFD). C57BL/6j mice were fed either a control diet or HFD with or
      without RM oil for 12 weeks. The results indicate that RM oil supplementation
      decreases fat infiltration of the liver from 43.8% to 6.2%, improving the hepatic
      oxidative state, insulin levels, HOMA index, and both body weight and adipose
      tissue weight of HFD plus RM treated animals compared to HFD without
      supplementation. In addition, the DHA concentration in the liver was
      significantly increased in HFD fed mice with RM oil compared to HFD (3 vs. 1.6 g
      per 100 g FAME). The n-6/n-3 ratio was not significantly modified by treatment
      with RM. Our findings suggest that RM oil supplementation prevents the
      development of hepatic steatosis and the obese phenotype observed in HFD fed
      mice. 

PMID- 26218007
TI  - Differences in Drinking Patterns Between Female Nursing and Nonnursing Students.
AB  - This study compared the drinking patterns of 123 female nursing students with
      those of 185 female students of other majors enrolled beyond the freshman year at
      a large public university. High-risk drinking patterns did not vary significantly
      between the 2 groups, suggesting that students' drinking patterns reflected the
      norms of their institution. Prevention strategies geared at campus culture and
      that target students still enrolled in prerequisites may be needed to reduce
      alcohol abuse in nursing students. 

PMID- 26218008
TI  - Nursing Students With Physical Disabilities: Dispelling Myths and Correcting
      Misconceptions.
AB  - The purpose of this article is to describe barriers and facilitators faced by
      nursing students with disabilities (SWDs) to dispel myths and correct
      misconceptions, promote the utilization of the campus disability office, and make
      the case that current technical standards may be obsolete. While there is no "one
      size fits all" approach, there are resources and methods that are available to
      nurse educators that should be used to end discrimination against SWDs. 

PMID- 26218009
TI  - Impact of Simulation and Clinical Experience on Self-efficacy in Nursing
      Students: Intervention Study.
AB  - This study compared the effect of simulation and clinical experience timing on
      self-confidence/self-efficacy for the nursing process. Using a randomized, double
      crossover design, self-efficacy was measured 3 times. Although self-efficacy was
      significantly higher at time 1 for students who had clinical experience, there
      was no difference between the groups at the end of the course (time 2). Thus,
      simulation increased self-confidence/self-efficacy equivalently if placed either
      before or after clinical experience. 

PMID- 26218010
TI  - Diagnostic Nihilism Toward Low Back Pain: What Once Was Accepted, Should No
      Longer Be.

PMID- 26218011
TI  - Systemic lupus erythematosus presenting as rectal ulcer and longitudinal
      myelopathy.

PMID- 26218012
TI  - The expression of the imprinted gene pleckstrin homology-like domain family A
      member 2 in placental tissues of preeclampsia and its effects on the
      proliferation, migration and invasion of trophoblast cells JEG-3.
AB  - Preeclampsia (PE) is one of the most common hypertensive disorders and is a
      leading cause of morbidity and mortality for pregnant women and perinatal babies.
      Additionally, pleckstrin homology-like domain family A member 2 (PHLDA2) is
      associated with placental dysfunction. However, the effect of PHLDA2 on
      trophoblast cell proliferation, migration and invasion has not been investigated.
      In this study, 15 PE patients and 15 normal pregnant women were recruited and
      clinical characteristics were summarized. Pleckstrin homology-like domain family
      A member 2 levels in placental tissues were examined using real-time PCR and
      western blot. Overexpression plasmid and PHLDA2 siRNA was introduced into JEG-3
      cells, respectively. Cell proliferation was measured using MTT assay and flow
      cytometry. Cell migration and invasion capacities were assessed by wound healing
      and Transwell assays. It was found that PE patients collectively presented
      proteinuria, elevated systolic blood pressure (SBP) and diastolic blood pressure
      (DBP), and lower gestational ages and birth weights. Pleckstrin homology-like
      domain family A member 2 levels in the preeclamptic placenta were significantly
      upregulated. Pleckstrin homology-like domain family A member 2 overexpression
      significantly arrested cells in the G0/G1 phase, inhibited cell proliferation and
      suppressed the migration and invasion of JEG-3 cells. Pleckstrin homology-like
      domain family A member 2 knockdown significantly blocked the cells in the S phase
      of the cell cycle. Knockdown of PHLDA2 alleviated the inhibition on the migration
      and invasion of trophoblast cells JEG-3. These findings illustrate that PHLDA2
      may participate in PE pathogenesis and indicate its potential application in the
      early diagnosis of PE. 

PMID- 26218013
TI  - Atmospheric Mercury in the Barnett Shale Area, Texas: Implications for Emissions
      from Oil and Gas Processing.
AB  - Atmospheric mercury emissions in the Barnett Shale area were studied by employing
      both stationary measurements and mobile laboratory surveys. Stationary
      measurements near the Engle Mountain Lake showed that the median mixing ratio of
      total gaseous mercury (THg) was 138 ppqv (140 +/- 29 ppqv for mean +/- S.D.)
      during the June 2011 study period. A distinct diurnal variation pattern was
      observed in which the highest THg levels appeared near midnight, followed by a
      monotonic decrease until midafternoon. The influence of oil and gas (ONG)
      emissions was substantial in this area, as inferred from the i-pentane/n-pentane
      ratio (1.17). However, few THg plumes were captured by our mobile laboratory
      during a ~3700 km survey with detailed downwind measurements from 50 ONG
      facilities. One compressor station and one natural gas condensate processing
      facility were found to have significant THg emissions, with maximum THg levels of
      963 and 392 ppqv, respectively, and the emissions rates were estimated to be 7.9
      kg/yr and 0.3 kg/yr, respectively. Our results suggest that the majority of ONG
      facilities in this area are not significant sources of THg; however, it is highly
      likely that a small number of these facilities contribute a relatively large
      amount of emissions in the ONG sector. 

PMID- 26218014
TI  - Comparison of the Masticatory Functions of Complete Dentures and Implant-Retained
      Overdentures.
AB  - The aim of this study was to evaluate the changes in the masticatory functions of
      complete dentures before and after the insertion of a LOCATOR attachment. The
      mixing ability index with a two-colored paraffin wax cube was used to quantify
      masticatory performance. In addition, degree of satisfaction with the treatment
      was assessed using a visual analog scale. The mixing ability index for the
      implant-retained overdentures and the complete dentures were calculated (-0.03+/
      1.38 and -2.10+/-1.57, respectively), as were the visual analog scales of the
      implant-retained overdentures and the complete dentures (8.9+/-1.5 and 4.3+/-1.7,
      respectively). The paired t test revealed significant improvements (P<.001).

PMID- 26218015
TI  - Dental Implant Therapy for a Child with X-linked Hypohidrotic Ectodermal
      Dysplasia--Three Decades of Managed Care.
AB  - PURPOSE: The aim was to report on oral rehabilitation of a boy with X-linked
      hypohidrotic ectodermal dysplasia (XLHED) and anodontia of the mandible between
      ages 3 and 33 years where treatment involved dental implants and oral care
      management by a multidisciplinary team of specialists. MATERIALS AND METHODS:
      This case history report describes the clinical management of a boy born in 1979
      with XLHED and anodontia of the mandible. Two implants were successfully placed
      in the anterior region of the mandible in 1985. Genetic analysis later verified
      the diagnosis by confirming a mutation in the EDA gene. The case description was
      based on review of the patient records and assessment of orofacial function.
      RESULTS: The patient had satisfactory orofacial appearance and function
      throughout his youth. He is still caries-free at age 33 and has experienced only
      minor oral complications. Dental management began at age 3, when he received a
      maxillary removable dental prosthesis. At age 7, he received a mandibular implant
      supported overdenture. After two more implants in the mandible and orthodontic
      treatment in the maxilla, his oral rehabilitation was completed at age 22 with
      maxillary tooth-supported and mandibular implant-supported fixed dental
      prostheses. Regular follow-ups provided supervision of oral hygiene, caries
      prevention, and prosthetic maintenance. CONCLUSION: This long-term follow-up of a
      child with XLHED and anodontia in the mandible supports the use of dental
      implants, with consideration given to the dense bone quality associated with the
      diagnosis, to establish good orofacial function and appearance from childhood
      onward.

PMID- 26218016
TI  - The Effects of Margin Curvature on Load at Fracture of Ceramic Crowns.
AB  - PURPOSE: Despite the high fracture strength of modern dental core ceramics,
      fractures are a common cause of clinical failures. The aim of this study was to
      use a clinically relevant test method to evaluate the effect of the curvature of
      the cervical crown margins on load at fracture. MATERIALS AND METHODS: Thirty
      zirconia crowns and 30 glass-ceramic crowns were produced for three premolar
      preparations with variation in the approximal crown margin curvature: low
      curvature (r=12 mm), moderate curvature (r=2.5 mm), and high curvature (r=1.5).
      The crowns were loaded until fracture with a method that mimics clinical fracture
      modes. RESULTS: Statistically significant differences were found among both crown
      margin curvature and material groups (P<.001). Most fractures originated from pre
      existing flaws. CONCLUSION: A moderate to low curvature of the crown margins
      increases crown strength compared with a high curvature.

PMID- 26218017
TI  - Influence of Articulating Paper Thickness on Occlusal Contacts Registration: A
      Preliminary Report.
AB  - The objective of this preliminary study was to determine if the occlusal contact
      surface registered with an articulating paper during fixed prosthodontic
      treatment was contained within the area marked on a thicker articulating paper.
      This information would optimize any necessary occlusal adjustment of a
      prosthesis' veneering material. A convenience sample of 15 patients who were
      being treated with an implant-supported fixed singleunit dental prosthesis was
      selected. Occlusal registrations were obtained from each patient using 12-MUm, 40
      MUm, 80-MUm, and 200-MUm articulating paper. Photographs of the occlusal
      registrations were obtained, and pixel measurements of the surfaces were taken
      and overlapped for comparison. The results showed that the thicker the
      articulating paper, the larger the occlusal contact area obtained. The
      differences were statistically significant. In all cases, the occlusal
      registrations obtained with the thinnest articulating paper were contained within
      the area marked on the thickest articulating paper. The results suggested that
      the use of thin articulating papers (12-MUm or 40-MUm) can avoid unnecessary
      grinding of veneering material or teeth during occlusal adjustment. 

PMID- 26218018
TI  - Changes in Lower Facial Height and Facial Esthetics with Incremental Increases in
      Occlusal Vertical Dimension in Dentate Subjects.
AB  - PURPOSE: To determine if there are objective changes in lower facial height and
      subjective changes in facial esthetics with incremental increases in occlusal
      vertical dimension in dentate subjects. MATERIALS AND METHODS: Twenty subjects of
      four different races and both sexes with a Class I dental occlusion had custom
      diagnostic occlusal prostheses (mandibular overlays) fabricated on casts mounted
      on a semi-adjustable articulator. The overlays were fabricated at 2-mm, 3-mm, 4
      mm, and 5-mm openings of the anterior guide pin of a semi-adjustable articulator.
      Direct facial measurements were made between pronasale and menton on each subject
      while wearing the four different overlays. Thereafter, two digital photographs
      (frontal and profile) were taken for each subject at maximum intercuspation
      (baseline) and wearing each of the four mandibular overlays. The photographs of
      eight subjects were standardized and displayed in a random order to 60 judges
      comprising 30 laypeople, 15 general dentists, and 15 prosthodontists. Using a
      visual analog scale, each judge was asked to rate the facial esthetics twice for
      each of the 80 images. RESULTS: For objective changes, although an anterior guide
      pin-lower facial height relationship of 1:0.63 mm was observed, the findings were
      not correlated (P>.20). For subjective changes, the visual analog scale ratings
      of judges were uncorrelated with increases in anterior guide pin opening up to 5
      mm, irrespective of the judge's background status or the sexes of the judges or
      the subjects (P>.80). CONCLUSIONS: Incremental increases in anterior guide pin
      opening up to 5 mm did not correlate to similar increases in lower facial height.
      Additionally, it made no difference in a judge's evaluation of facial esthetics
      irrespective of the judge's background status (layperson, general dentist, or
      prosthodontist) or sex.

PMID- 26218019
TI  - Peri-implant Biofilm Formation on Luting Agents Used for Cementing Implant
      Supported Fixed Restorations: A Preliminary In Vivo Study.
AB  - This study investigated subgingival peri-implant biofilm formation on four luting
      agents (Kerr TempBond, Harvard Dental Harvard Cement, 3M ESPE RelyX Unicem, and
      Kuraray Panavia F 2.0) under realistic in situ conditions. Samples of the luting
      agents were positioned in the subgingival area of healing abutments, and the
      biofilm accumulation on the samples at the interface between luting agent and
      titanium and on the smooth titanium surface was investigated using scanning
      electron microscopy. In comparison to plane titanium surfaces, interfaces between
      implant abutment, cement, and suprastructure showed an increased bacterial
      accumulation and should therefore be regarded as predisposing substrates for peri
      implant biofilm formation. 

PMID- 26218020
TI  - The Use of High-Frequency Ultrasound in the Measurement of Thickness of the
      Maxillary Attached Gingiva.
AB  - PURPOSE: Ultrasonography has been extensively explored in dentistry because of
      its several diagnostic advantages. The purpose of this study was to determine the
      thickness of the maxillary attached gingiva with the use of a high-frequency
      ultrasound in subjects with sex-, age- and smoking-related differences. MATERIALS
      AND METHODS: A total of 100 healthy subjects (70 women and 30 men, age range: 18
      to 55 years) were included. A special B-scan unit was used to measure the soft
      tissue thickness in the buccal and palatal attached gingiva in the maxillary
      arch. Aquasonic 100 Ultrasound Gel (Parker Laboratories) was used as coupling
      medium. Student t test was used for statistical analysis of the subgroups with
      different parameters with significance set at P<.05. RESULTS: A total of 2,734
      measurements showed that male nonsmokers have a significantly thicker fixed
      gingiva than nonsmoking women and that age does not seem to have great influence
      on the thickness of the gingiva. Smoking had a significant effect, but only on
      the oral maxillary gingival tissues of women. The palatal gingiva was found to be
      significantly thicker in female smokers than in nonsmoking females. CONCLUSIONS:
      Measurement of gingival thickness for different purposes using a B-scan
      ultrasonic device appears to be a reliable method. Sex- and smoking-related
      differences in the gingival thickness exist only on the palatal side among women.

PMID- 26218021
TI  - Assessment of Artificial Teeth Setup Device: A Three-Dimensional Model Analysis.
AB  - This study assessed the use of the commercial artificial teeth setup device Staub
      Cranial System (Neu-Ulm) in Asian subjects. Fourteen completely dentate Thai
      volunteers were randomly recruited. Study casts (control group) and duplicated
      casts (experimental group) of all subjects were prepared. Artificial teeth were
      replaced on duplicated casts according to the manual. Computed tomography scans
      of all casts were performed. Intercanine width, intermolar width, incisocervical
      length, and occlusal plane were investigated. The length of the natural
      mandibular left central incisor was smaller than the reconstructed one. The
      reconstructed occlusal plane was more parallel to the hamular-incisive papilla
      plane than that of the control group. 

PMID- 26218022
TI  - Distribution of Forces in Distal-Extension Removable Partial Dentures With and
      Without Retromolar Pad Coverage: A Pilot In Vivo Study.
AB  - This study compared the distribution of forces in relation to the area covered by
      the denture base. Seven participants were fitted with a loading device on the
      maxilla and were guided to bite on an experimental mandibular denture. The
      denture base was progressively shortened from full coverage of the retromolar
      pad. One-way analysis of variance (P<.05) was performed, and no significant
      difference was found among the four denture base lengths in relation to force
      distribution. Within the limitations of this study, the authors conclude that the
      area covered by the retromolar pad has little influence on force distribution
      during loading.

PMID- 26218023
TI  - Influence of Different Surface Characteristics on Peri-implant Tissue Behavior: A
      Six-Year Prospective Report.
AB  - PURPOSE: The aim of this study was to evaluate the behavior of hard and soft
      tissue around implants with different surface treatments. MATERIALS AND METHODS:
      Eight patients were identified for this study. Each patient received at least 2
      implants (1 control, 1 test) into an edentulous quadrant, for a total of 10 pairs
      of implants. Two types of implants were used: hybrid implants (control) with a
      dual acid-etched surface in their apical portion and a machined coronal part, and
      test implants with an acid-etched surface throughout their entire length.
      Standardized periapical radiographs were taken at baseline, 3 months, 6 months,
      and 1 year post implant placement and then annually until the 6-year follow-up.
      Bleeding on probing (BOP) and Plaque Index (PI) were recorded annually. Probing
      depth (PD) was recorded at the 6-year follow-up. RESULTS: Moderate crestal bone
      remodeling was observed during the 1-year postimplant placement evaluation
      (P=.001), and test implants revealed smaller marginal bone resorption (P=.030).
      No significant changes in bone level were observed between the 1-year and the 6
      year follow-up appointments, and a significantly smaller bone resorption was
      found at test implants. No statistically significant differences in bone
      resorption were found between maxilla and mandible. No statistically significant
      differences were detected between test and control implants for BOP, PI, or PD.
      CONCLUSIONS: The preliminary results suggest that implant surface characteristics
      might affect the bone remodeling phase subsequent to the surgical trauma.
      However, once osseointegration was established, implant surfaces did not affect
      bone maintenance over time. Implant surfaces did not affect soft tissue behavior.
      The results of this pilot study need to be confirmed in a study with a larger
      sample size and over a longer time frame.

PMID- 26218024
TI  - Preliminary Evaluation of Mechanical Properties of Co-Cr Alloys Fabricated by
      Three New Manufacturing Processes.
AB  - A preliminary tensile test was performed to evaluate the mechanical properties of
      cobalt-chromium (Co-Cr) alloys fabricated by three new manufacturing processes:
      metal milling, milling for soft metal, and rapid prototyping (n=6). For
      comparison, the three alloy materials were also used to fabricate specimens by a
      casting procedure. In all groups tested, the proof strength and elongation were
      over 500 MPa and 2%, respectively. The milled soft alloy in particular showed a
      substantially greater elongation, whereas the alloy fabricated by rapid
      prototyping exhibited a higher proof strength.

PMID- 26218025
TI  - Relationship Between Quality of Life Related to Voice and Oral Health in Elderly
      People.
AB  - This preliminary study investigated the influence of different oral prosthodontic
      interventions on quality of life related to voice and oral health in elderly
      people and the relation between these conditions. Forty-five elderly people who
      had completed prosthodontic rehabilitation treatments were divided into three
      groups according to dental conditions and answered two protocols: voice-related
      quality of life and oral health impact profile. Despite the small sample size,
      the elderly people in this study presented no differences between the groups and
      showed a relationship between oral and vocal health aspects. 

PMID- 26218026
TI  - The Oral Health-Related Quality of Life in State Institutionalized Older Adults
      in Malta.
AB  - PURPOSE: The objective of this study was to determine the oral health-related
      quality of life in state institutionalized older adults and correlate it to their
      oral health status. MATERIALS AND METHODS: A group of 278 older adults (average
      age: 83.5+/-6.5 years) from 9 state institutions in Malta was randomly selected.
      Participants were clinically examined and answered three questionnaires (Oral
      Health Impact Profile [OHIP-14], Geriatric Oral Health Assessment Index [GOHAI],
      and Denture Satisfaction). RESULTS: Oral health-related quality of life
      measurements were significantly associated with pocket depth (OHIP-14 and GOHAI,
      P<.05); decayed, missing, or filled teeth (OHIP-14 and GOHAI, P<.05); carious
      teeth (OHIP-14 and GOHAI, P<.05); number of missing teeth (OHIP-14 and GOHAI,
      P<.05); and maxillary and mandibular dentures (OHIP-14 and GOHAI, P<.0001).
      Denture satisfaction was associated with denture age (P=.010) and types of
      prostheses (P<.05). CONCLUSION: Institutionalized older adults have high levels
      of oral disease. Although oral health-related quality of life is generally good,
      those participants with a poorer oral health-related quality of life had
      significant associations with poor oral health. However, the extent varies with
      the individual's perception of good health.

PMID- 26218027
TI  - Denture-Related Biomechanical Factors for Fixed Partial Dentures Retained on
      Short Dental Implants.
AB  - Prosthodontically driven biomechanical considerations are essential for longterm
      successful outcomes in dental implant therapy. Correct protocols seek to preclude
      potential consequences associated with functional and parafunctional occlusal
      overload such as screw loosening, component fracture, compromised marginal bone
      maintenance, and the integrity of the induced osseointegration response. Other
      concerns also need to be addressed, more especially when other implants are
      selected, for example: bridge insertion torque (BIT) in cases of immediate
      loading, cantilever length-anteroposterior spread ratio (CL-AP), overall crown-to
      implant ratio (oCIR), total bone-to-implant surface area (tBICA), and the status
      of the opposing dentition. In spite of promising clinical results, evidence-based
      clinical protocols demand that such biomechanical limits still need to be
      determined. 

PMID- 26218028
TI  - Effect of Opaque Layer Application on the Color of Resin Composites Used to Fill
      Access Openings of Screw-Retained Implant Restorations.
AB  - The purpose of this preliminary in vitro study was to evaluate the effect of an
      opaque layer and application of resin composite in dual colors on the DeltaE
      values of resin composites used to fill access openings of screw-retained implant
      restorations. Sixty cylindrical nickel-chromium metal molds with a central
      channel simulating a posterior screw-retained, implant-supported, porcelain-fused
      to-metal crown were cast. Access openings were filled with combinations of
      opaquer, enamel composite (A2E), dentin composite (A2B and A3B), and resilient
      composite. DeltaE values differed significantly among the groups (P<.01). The
      combination of opaque layer and dual color resin composites of shades A2E and A3B
      resulted in significantly lower DeltaE values than the other groups (P<.01).

PMID- 26218029
TI  - Evaluation of Masticatory Efficiency and QoL Improvements After Prosthetic
      Rehabilitation of Mandibular Cancer Patients Reconstructed with a Fibula Free
      Flap.
AB  - PURPOSE: The purpose of this noninferiority study was to determine whether
      removable or implant-supported fixed dental prostheses restored patients'
      abilities to preoperative levels after cancer removal in the mandible. MATERIALS
      AND METHODS: Ten patients who had undergone mandibular resection to remove cancer
      and subsequent reconstruction with microvascularized free fibula flaps were
      examined in this study. Five patients were rehabilitated with removable
      prostheses and five received implant-supported fixed prostheses. Health-related
      quality of life was evaluated using the Head and Neck (H&N30) questionnaire.
      Kruskal-Wallis nonparametric analysis of variance and Tamhane's T2 test were used
      to analyze results in comparison with a control group composed of 10 subjects
      with Class I natural dentition. RESULTS: Masticatory efficiency among the three
      groups of patients differed significantly (P=.003); in particular, that of the
      patients who received removable prostheses was not inferior to that of the
      control subjects (P=.019). Analysis of responses to the Head and Neck module of
      the Quality of Life Questionnaire showed no significant difference between
      patients with fixed dentures and patients with removable dentures. CONCLUSIONS:
      There is no apparent difference in quality of life between patients using implant
      supported fixed prostheses and those using removable prostheses. Regarding
      masticatory efficiency, when feasible, the use of implant-supported fixed
      prostheses is recommended in patients who have undergone free fibula flap
      surgery, although the removable prostheses also were not inferior in patients who
      underwent no surgery.

PMID- 26218030
TI  - Prosthetic Treatment Concepts for the Reduced Dentition in German Dental Schools.
AB  - This survey of German dental schools sought to gain insight into the present
      prosthetic treatment concepts and their application in student and postgraduate
      education, as well as to compare the results to those from an identical 2002
      survey. A questionnaire, based on this issue, was sent via email to the
      chairpersons of all prosthetic departments of the German dental schools, and
      93.1% of the departments completed the questionnaire. Within the limitations of
      this survey, almost all treatment concepts for the reduced dentition are taught
      intensively at dental schools in Germany while some therapy forms are preferred. 

PMID- 26218031
TI  - Fractographic Study of the Interface Between Zirconia Y-TZP and Its Veneering
      Ceramic After Shear Strength Testing.
AB  - This study analyzed the shear strength and fracture characteristics of the
      interface between zirconia samples and their veneering ceramic compared with a
      metal-ceramic and a lithium disilicate glass-ceramic control group together with
      an assessment of the possible relationship between the fracture characteristics
      and the recorded shear strength. The greatest shear strengths corresponded to the
      lithium disilicate glass-ceramic control group followed by the metal-ceramic
      control group, with lesser strengths in the zirconia groups. Since the
      fractographic study showed cohesive-type failure to predominate in the zirconia
      samples, it is concluded that improvements are needed in the veneering ceramic
      and liner used in zirconia restorations. 

PMID- 26218032
TI  - Long-term safety and efficacy of recombinant factor VIII Fc fusion protein
      (rFVIIIFc) in subjects with haemophilia A.
AB  - INTRODUCTION: The safety, efficacy and prolonged half-life of recombinant factor
      VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe
      haemophilia A was demonstrated in the phase 3 A-LONG and Kids A-LONG studies.
      Here, we report interim safety and efficacy data from the rFVIIIFc extension
      study, ASPIRE (ClinicalTrials.gov #NCT01454739). METHODS: Eligible subjects could
      enrol in ASPIRE upon completing A-LONG or Kids A-LONG. There were four treatment
      groups: individualized prophylaxis; weekly prophylaxis; modified prophylaxis (for
      subjects in whom optimal treatment could not be achieved with individualized or
      weekly prophylaxis); and episodic treatment. The primary endpoint was development
      of inhibitors. RESULTS: A total of 150 A-LONG subjects and 61 Kids A-LONG
      subjects enrolled in ASPIRE. As of the interim data cut (6 January 2014), the
      median time on study was 80.9 (A-LONG) and 23.9 (Kids A-LONG) weeks. The majority
      of subjects (A-LONG, 92.0%; Kids A-LONG, 57.4%) had >=100 cumulative rFVIIIFc
      exposure days. No inhibitors were observed. Adverse events were generally
      consistent with those expected in the general haemophilia A population. Median
      annualized bleeding rates (ABRs) were low with individualized [A-LONG: 0.66; Kids
      A-LONG: 0.00 (<6 years old), 1.54 (6 to <12 years old)], weekly (A-LONG: 2.03)
      and modified (A-LONG: 1.97) prophylaxis. There was no change in prophylactic
      infusion frequency or total weekly prophylactic dose in the majority of subjects
      from A-LONG and Kids A-LONG. CONCLUSION: Interim data from ASPIRE confirm the
      long-term safety of rFVIIIFc and the maintenance of a low ABR with extended
      interval prophylactic dosing in patients with severe haemophilia A.

PMID- 26218033
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with
      malignancies.
AB  - BACKGROUND: Malignancy is known to be associated with an increased mortality rate
      in patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
      (TEN). However, risk factors contributing to the poor prognosis of patients with
      SJS/TEN with malignancies remain undefined. OBJECTIVES: To explore the potential
      involvement of malignancy and its related factors contributing to the poor
      outcome of SJS/TEN, in a retrospective study. METHODS: In total 517 patients with
      SJS/TEN were enrolled. Forty-seven who sustained various types of malignancies
      were analysed for numerous malignancy-related factors, including cancer types,
      clinical stages and chemotherapies given or not before the onset of SJS/TEN.
      RESULTS: We found that the mortality rate of patients with SJS/TEN with
      malignancies was higher than that of patients without malignancies (32%, 15/47
      vs. 8.5%, 40/470, respectively) (P < 0.001). The use of phenytoin was
      significantly higher in the malignancy group. The presence of hepatocellular
      carcinoma (80%, four of five; P < 0.001; odds ratio 43) and colorectal cancer
      (67%, two of three; P = 0.022; odds ratio 21.5) significantly increased the death
      rate of patients with SJS/TEN, whereas lung cancer and urothelial carcinoma did
      not. Patients who had received ongoing or recent chemotherapy showed higher
      mortality than those without chemotherapy (P = 0.022; odds ratio 4.95).
      Furthermore, among the 47 patients with SJS/TEN with malignancies, lower serum
      albumin, haemoglobin and platelet count were detected in the deceased patients
      than in the surviving patients before the onset of SJS/TEN. CONCLUSIONS: Our
      results suggest that several factors related to malignancies, such as specific
      cancer types, chemotherapy and malnutrition, may contribute to poor prognosis in
      patients with malignancies developing SJS/TEN.

PMID- 26218034
TI  - Asymmetric signal amplification for simultaneous SERS detection of multiple
      cancer markers with significantly different levels.
AB  - Simultaneous detection of cancer biomarkers holds great promise for the early
      diagnosis of different cancers. However, in the presence of high-concentration
      biomarkers, the signals of lower-expression biomarkers are overlapped. Existing
      techniques are not suitable for simultaneously detecting multiple biomarkers at
      concentrations with significantly different orders of magnitude. Here, we propose
      an asymmetric signal amplification method for simultaneously detecting multiple
      biomarkers with significantly different levels. Using the bifunctional probe, a
      linear amplification mode responds to high-concentration markers, and quadratic
      amplification mode responds to low-concentration markers. With the combined
      biobarcode probe and hybridization chain reaction (HCR) amplification method, the
      detection limits of microRNA (miRNA) and ATP via surface-enhanced Raman
      scattering (SERS) detection are 0.15 fM and 20 nM, respectively, with a
      breakthrough of detection concentration difference over 11 orders of magnitude.
      Furthermore, successful determination of miRNA and ATP in cancer cells supports
      the practicability of the assay. This methodology promises to open an exciting
      new avenue for the detection of various types of biomolecules. 

PMID- 26218035
TI  - Effectiveness and economic evaluation of self-help educational materials for the
      prevention of smoking relapse: randomised controlled trial.
AB  - BACKGROUND: Most people who quit smoking successfully for a short period will
      return to smoking again in 12 months. A previous exploratory meta-analysis
      indicated that self-help booklets may be effective for smoking relapse prevention
      in unaided quitters. OBJECTIVES: This study aimed to evaluate the effectiveness
      of a set of self-help educational booklets to prevent smoking relapse in people
      who had stopped smoking with the aid of behavioural support. DESIGN: This is an
      open, randomised controlled trial and qualitative process evaluation. Trial
      participants were randomly allocated to one of two groups, using a simple
      randomisation process without attempts to stratify by participant
      characteristics. The participant allocation was 'concealed' because the
      recruitment of quitters occurred before the random allocation. SETTING: Short
      term quitters were recruited from NHS Stop Smoking Clinics, and self-help
      educational materials were posted to study participants at home. PARTICIPANTS: A
      total of 1407 carbon monoxide (CO)-validated quitters at 4 weeks after quit date
      in NHS Stop Smoking Clinics. The trial excluded pregnant women and quitters who
      were not able to read the educational materials in English. INTERVENTIONS:
      Participants in the experimental group (n = 703) received a set of eight revised
      Forever Free booklets, and participants in the control group (n = 704) received a
      single leaflet that is currently given to NHS patients. MAIN OUTCOME MEASURES:
      Follow-up telephone interviews were conducted 3 and 12 months after quit date.
      The primary outcome was prolonged, CO-verified abstinence from months 4 to 12
      during which time no more than five cigarettes were smoked. The secondary
      outcomes included self-reported abstinence during the previous 7 days at 3 and 12
      months, CO-verified abstinence at 12 months, costs (NHS and NHS and participant
      medication costs perspectives) and quality-adjusted life-years. Logistic
      regression analyses were conducted to investigate effect-modifying variables. A
      simultaneous qualitative process evaluation was conducted to help interpret the
      trial results. RESULTS: Data from 1404 participants were used for the final
      analysis, after excluding three participants who died before the 12-month follow
      up. The proportion with prolonged abstinence from months 4 to 12 after quit date
      was 36.9% in the intervention group and 38.6% in the control group. There was no
      statistically significant difference between the groups (odds ratio 0.93, 95%
      confidence interval 0.75 to 1.15; p = 0.509). There were no statistically
      significant differences between the groups in secondary smoking outcomes. People
      who reported knowing risky situations for relapse and using strategies to handle
      urges to smoke were less likely to relapse. However, there were no differences
      between the groups in the proportion of participants who reported that they knew
      any more about coping skills, and no differences in reported use of strategies to
      cope with urges to smoke between the trial groups. The qualitative study found
      that some quitters considered self-help booklets unhelpful for smoking relapse
      prevention, although positive feedback by participants was common. CONCLUSIONS:
      Among quitters who had stopped smoking with the aid of intensive behavioural
      support, there was no significant difference in the likelihood of smoking relapse
      between those who subsequently received a set of eight revised Forever Free
      booklets and those who received a single leaflet. Although many people had
      suboptimal strategies to prevent relapse and most relapsed, the Forever Free
      booklets proved an ineffective medium for teaching them the skills to prevent
      relapse. Further research should focus on interventions that may increase the use
      of coping skills when required. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN36980856.

PMID- 26218036
TI  - The role of microRNAs in the pathogenesis of HIV-related lymphomas.
AB  - The incidence of HIV-related lymphomas (HRLs) is increased by 60-100 times in
      patients with HIV. When compared to the general population, patients with HRLs
      often present with extranodal lymphoid proliferation, most frequently of the
      gastrointestinal tract, central nervous system, liver and bone marrow. MicroRNAs
      (miRs) are non-coding double-stranded RNA molecules of 18-25 nucleotides that
      regulate post-translational gene expression by inhibiting translation or
      promoting degradation of messenger RNA complementary sequences. Before their
      discovery, tumorigenesis was thought to have been caused by the alteration of
      protein-coding oncogenes and tumor-suppressor genes, but once identified in B
      cell chronic lymphocytic leukemia, miRs function as either oncogenes or tumor
      suppressor genes was confirmed in different types of malignancies. Since miRs are
      clearly involved in tumorigenesis in many cancers, their role in HRLs is now
      receiving attention. A few studies have been conducted thus far in some HRLs on
      the involvement of miR in the pathogenesis of lymphoid malignancies. Since B-cell
      lymphomas arise from various stages of B-cell development in both HIV-infected
      and HIV-naive patients, investigators have tried to determine the different miR
      signatures in B-cell development. As classic immunohistochemistry staining is
      sometimes not enough for the differential diagnosis of HRLs, in the present
      review, we have described the potential use of miRs in the prognosis and
      diagnosis of these diseases. 

PMID- 26218037
TI  - Correction to "Reinvestigating the Reaction of 1H-Pyrazol-5-amines with 4,5
      Dichloro-1,2,3-dithiazolium Chloride: A Route to Pyrazolo[3,4-c]isothiazoles and
      Pyrazolo[3,4-d]thiazoles".

PMID- 26218038
TI  - Retrieval of migrated pancreatic stent: "stent-in-stent" technique.

PMID- 26218039
TI  - Endoscopic ultrasound-guided antegrade bile duct stone treatment followed by
      direct peroral transhepatic cholangioscopy in a patient with Roux-en-Y
      reconstruction.

PMID- 26218040
TI  - Endoscopic ultrasound-guided choledochojejunostomy with a lumen-apposing metal
      stent: a shortcut for biliary drainage.

PMID- 26218041
TI  - Endoscopic full-thickness resection of a nonlifting adenoma in an ileal pouch
      using an over-the-scope full-thickness resection device.

PMID- 26218042
TI  - Acute pancreatitis-like bile leakage around the portal vein system after
      endoscopic ultrasound-guided choledochoduodenostomy.

PMID- 26218043
TI  - Endoscopic resection of an esophageal duplication cyst with spraying of anhydrous
      alcohol.

PMID- 26218044
TI  - Endoscopic ultrasound-guided duodenojejunal anastomosis to treat postsurgical
      Roux-en-Y hepaticojejunostomy stricture: a dream or a reality?

PMID- 26218045
TI  - Giant inflammatory pseudotumor of the larynx treated endoscopically by a
      gastroenterologist using submucosal dissection.

PMID- 26218046
TI  - Ascaris lumbricoides causing obscure gastrointestinal bleeding detected by double
      balloon enteroscopy.

PMID- 26218047
TI  - Vast collection of foreign bodies in the stomach presenting as acute
      gastrointestinal bleeding in a patient with schizophrenia.

PMID- 26218048
TI  - Bone Conduction Thresholds: May the Force Be with You.

PMID- 26218049
TI  - Executive Summary: Evidence-Based Best Practice Guideline for Adult Patients with
      Severe-to-Profound Unilateral Sensorineural Hearing Loss.

PMID- 26218050
TI  - Comparison of Multichannel Wide Dynamic Range Compression and ChannelFree
      Processing Strategies on Consonant Recognition.
AB  - BACKGROUND: Both wide dynamic range compression (WDRC) and ChannelFree (CF)
      processing strategies in hearing aids were designed to improve listener comfort
      and consonant identification, yet few studies have actually compared them.
      PURPOSE: To determine whether CF processing provides equal or better consonant
      identification and subjective preference than WDRC. RESEARCH DESIGN: A repeated
      measures randomized design was used in which each participant identified
      consonants from prerecorded nonsense vowel-consonant-vowel syllables in three
      conditions: unaided, aided using CF processing, and aided using WDRC processing.
      For each of the three conditions, syllables were presented in quiet and in a
      speech-noise background. Participants were also asked to rate the two processing
      schemes according to overall preference, preference in quiet and noise, and sound
      quality. STUDY SAMPLE: Twenty adults (seven females; mean age 69.7 yr) with >=1
      yr of hearing aid use participated. Ten participants had previous experience
      wearing aids with WDRC, and 10 had previous experience with CF processing.
      Participants were tested with both WDRC and CF processing. DATA COLLECTION AND
      ANALYSIS: Number of consonants correct were measured and used as the dependent
      variable in analyses of variance with subsequent post hoc testing. For subjective
      preference, a listener rating form was employed with subsequent chi2 analysis.
      RESULTS: Overall results showed that signal-processing strategy did not
      significantly affect consonant identification or subjective preference, nor did
      previous hearing aid use influence results. Listeners with audiometric slopes
      exceeding 11 dB per octave, however, preferred CF processing and performed better
      in noise with CF processing. CONCLUSION: CF processing is a viable alternative to
      WDRC for listeners with more severely sloping audiometric contours.

PMID- 26218051
TI  - Evaluation of Extended-Wear Hearing Technology for Children with Hearing Loss.
AB  - BACKGROUND: Research shows that many older children and teenagers who have mild
      to moderately severe sensorineural hearing loss do not use their hearing
      instruments during all waking hours. A variety of reasons may contribute toward
      this problem, including concerns about cosmetics associated with hearing aid use
      and the inconvenience of daily maintenance associated with hearing instruments.
      Extended-wear hearing instruments are inserted into the wearer's ear canal by an
      audiologist and are essentially invisible to outside observers. PURPOSE: The goal
      of this study was to evaluate the potential benefits and limitations associated
      with use of extended-wear hearing instruments in a group of children with hearing
      loss. RESEARCH DESIGN: A two-way repeated measures design was used to examine
      performance differences obtained with the participants' daily-wear hearing
      instruments versus that obtained with extended-wear hearing instruments. STUDY
      SAMPLE: Sixteen children, ages 10-17 yr old, with sensorineural hearing loss
      ranging from mild to moderately severe. DATA COLLECTION AND ANALYSIS: Probe
      microphone measures were completed to evaluate the aided output of device.
      Behavioral test measures included word recognition in quiet, sentence recognition
      in noise, aided warble-tone thresholds, and psychophysical loudness scaling.
      Questionnaires were also administered to evaluate subjective performance with
      each hearing technology. RESULTS: Data logging suggested that many participants
      were not using their daily-wear hearing instruments during all waking hours (mean
      use was less than 6 h/day). Real ear probe microphone measurements indicated that
      a closer fit to the Desired Sensation Level Version 5 prescriptive targets was
      achieved with the children's daily-wear instruments when compared to the extended
      wear instruments. There was no statistically significant difference in
      monosyllabic word recognition at 50 or 60 dBA obtained with the two hearing
      technologies. Sentence recognition in noise obtained with use of the extended
      wear devices was, however, significantly better than what was obtained with the
      daily-wear hearing aids. Aided warble-tone thresholds indicated significantly
      better audibility for low-level sounds with use of the daily-wear hearing
      technology, but loudness scaling results produced mixed results. Specifically,
      the participants generally reported greater loudness perception with use of their
      daily-wear hearing aids at 2000 Hz, but use of the extended-wear hearing
      technology provided greater loudness perception at 4000 Hz. Finally, the
      participants reported higher levels of subjective performance with use of the
      extended-wear hearing instruments. CONCLUSIONS: Although some measures suggested
      that daily-wear hearing instruments provided better audibility than the extended
      wear hearing devices, word recognition in quiet was similar with use of the two
      technologies, and sentence recognition in noise was better with the extended-wear
      hearing technology. In addition, the participants in this study reported better
      subjective benefit associated with the use of extended-wear hearing technology.
      Collectively, the results of this study suggest that extended-wear hearing
      technology is a viable option for older children and teenagers with mild to
      moderately severe hearing loss.

PMID- 26218052
TI  - Age- and Gender-Specific Normative Information from Children Assessed with a
      Dichotic Words Test.
AB  - BACKGROUND: The most widely used assessment in the clinical auditory processing
      disorder (APD) battery is the dichotic listening test. New tests with normative
      information are helpful for assessment and cross-check of results for reliable
      diagnosis. PURPOSE: The Dichotic Words Test was developed for use in the clinical
      test battery for diagnosis of APD. The test stimuli were common single syllable
      words matched for average root-mean-square amplitude and each pair was temporally
      aligned at both onset and offset. The study was conducted to collect performance
      results from typically developing children to create normative information for
      the test. RESEARCH DESIGN: The study follows a cross-sectional design. STUDY
      SAMPLE: Typically developing children (n = 416) between the ages of 5 and 12 yr
      were recruited from schools in the community. There were 217 males and 199
      females in the study sample. Only children who passed a hearing screening were
      eligible to participate. DATA COLLECTION AND ANALYSIS: Scores for each ear were
      recorded during administration of the first free recall version of the test. Ear
      advantages based on results recorded for left and right ears were used to measure
      prevalence of right, left, and no ear advantages. Results for each listener's
      dominant and non-dominant ears and the absolute difference between them were put
      into the data analysis. Results were analyzed for normality and because no
      results were normally distributed, all further analyses were done with
      nonparametric statistical tests. Normative data for dominant and non-dominant ear
      scores and ear advantages were determined at the 95% confidence interval through
      bootstrapping methods with 1,000 samples. RESULTS: Children were divided into
      four age groups based on results in their dominant ears. Females generally
      performed better than males and the prevalence of a right-ear advantage was ~60%
      across all children tested. Normative lower-bound cut-off scores were established
      for males and females within each age group for dominant and non-dominant ear
      scores. Normative upper-bound cut-off scores were established for males and
      females within each age group for ear advantage scores. CONCLUSIONS: Normative
      information specific to age group and gender will be useful in clinical
      assessment for APD. Prevalence of left-ear advantage results in the sample may
      have been partly due to uncontrolled influences of voice-onset time in arranging
      the dichotic pairs.

PMID- 26218053
TI  - Bone Conduction Thresholds without Bone Vibrator Application Force.
AB  - BACKGROUND: Osseous bone conduction (BC) stimulation involves applying the
      clinical bone vibrator with an application force of about 5 Newton (N) to the
      skin over the cranial vault of skull bone (e.g., mastoid, forehead). In
      nonosseous BC (also called soft tissue conduction), the bone vibrator elicits
      hearing when it is applied to skin sites not over the cranial vault of skull
      bone, such as the neck. PURPOSE: To gain insight into the mechanisms of osseous
      and nonosseous BC. RESEARCH DESIGN: In general, thresholds were determined with
      the bone vibrator applied with about 5 N force directly to osseous sites
      (mastoid, forehead) on the head of the participants, as classically conducted in
      the clinic, and again without direct physical contact (i.e., 0 N force) achieved
      by coupling the bone vibrator to gel as in ultrasound diagnostic imaging, on the
      same or nearby skin sites (nonosseous BC). The participants were equipped with
      earplugs to minimize air-conducted stimulation. STUDY SAMPLE: In the first
      experiment, 10 normal-hearing participants were tested with stimulation (5 and 0
      N) at the forehead; in the second experiment, 10 additional normal-hearing
      participants were tested with stimulation at the mastoid (about 5 N) and at the
      nearby tragus and cavum concha of the external ear (0 N). RESULTS: The mean
      thresholds with 0 N were much better than might be expected from classical
      theories in response to stimulation by a bone vibrator, in the absence of any
      application force. The differences between the mean thresholds with the 0 N and
      the 5 N forces depended on condition, site, and stimulus frequency of the
      comparisons. The difference was 1.5 dB at 1.0 kHz on the forehead; ranged between
      10 and 12.5 dB at 1.0 kHz on the cavum and tragus (versus on the mastoid) and at
      2.0 and 4.0 kHz on the forehead; 17 and 19 dB at 2.0 kHz on the cavum and tragus
      (versus on the mastoid); reaching 32 dB only in a single condition (forehead at
      0.5 kHz). CONCLUSIONS: As it is unlikely that threshold intensity stimulation
      delivered with 0 N application force could have induced vibrations of the
      underlying or nearby bone, inducing osseous BC, the relatively low thresholds in
      the absence of any application force, together with the small differences between
      the thresholds with 0 N (gel/soft tissue, nonosseous) and 5 N force (osseous BC)
      lead to the suggestion that in most situations, the BC thresholds actually
      represent the nonosseous (soft tissue conduction) thresholds at the stimulation
      site.

PMID- 26218054
TI  - Characteristics of Pediatric Performance on a Test Battery Commonly Used in the
      Diagnosis of Central Auditory Processing Disorder.
AB  - BACKGROUND: Although central auditory processing disorder (CAPD) test battery
      performance has been examined in adults with neurologic lesions of the central
      auditory nervous system (CANS), similar data on children being referred for CAPD
      evaluations are sparse. PURPOSE: This study characterizes CAPD test battery
      performance in children using tests commonly administered to diagnose the
      disorder. Specifically, this study describes failure rates for various test
      combinations, relationships between CAPD tests used in the battery, and the
      influence of cognitive function on CAPD test performance and CAPD diagnosis. A
      comparison is also made between the performance of children with CAPD and data
      from patients with neurologic lesions of the CANS. RESEARCH DESIGN: A
      retrospective study. STUDY SAMPLE: Fifty-six pediatric patients were referred for
      CAPD testing. DATA COLLECTION AND ANALYSIS: Participants were administered four
      CAPD tests, including frequency patterns (FP), low-pass filtered speech (LPFS),
      dichotic digits (DD), and competing sentences (CS). In addition, they were given
      the Wechsler Intelligence Scale for Children (WISC). Descriptive analyses
      examined the failure rates of various test combinations, as well as how often
      children with CAPD failed certain combinations when compared with adults with
      CANS lesions. A principal components analysis was performed to examine
      interrelationships between tests. Correlations and regressions were conducted to
      determine the relationship between CAPD test performance and the WISC. RESULTS:
      Results showed that the FP and LPFS tests were most commonly failed by children
      with CAPD. Two-test combinations that included one or both of these two tests and
      excluded DD tended to be failed more often. Including the DD and CS test in a
      battery benefited specificity. Tests thought to measure interhemispheric transfer
      tended to be correlated. Compared with adult patients with neurologic lesions,
      children with CAPD tended to fail LPFS more frequently and DD less frequently.
      Both groups failed FP with relatively equal frequency. CONCLUSIONS: The two-test
      combination that showed the highest failure rate for children with CAPD was LPFS
      FP. Comparison with adults with CANS lesions, however, suggests that the
      mechanisms underlying LPFS performance in children need to be better understood.
      The two-test combination that showed the next highest failure rates among
      children with CAPD and did not include LPFS was CS-FP. If it is desirable to use
      a dichotic measure that has a lower linguistic load than CS then DD can be
      substituted for CS despite the slightly lower failure rate of the DD-FP battery.

PMID- 26218055
TI  - Recognition Performance of Interrupted Monosyllabic Words: The Effects of Ten
      Interruption Locations.
AB  - BACKGROUND: A previous experiment with 70 interrupted monosyllabic words
      demonstrated that recognition performance was influenced by the location of an
      interruption pattern (Wilson, 2014). The interruption paradigm (10
      interruptions/sec, 50% duty cycle periodic interruption) was referenced to word
      onset. The words were interrupted such that alternate 50-msec segments were
      parsed to separate files. In the 0-msec condition the first on-segment coincided
      with the word onset, whereas in the 50-msec condition the first on-segment
      occurred 50 msec after word onset. The 0- and 50-msec conditions were
      complementary halves. Recognition performance by young listeners was 19% better
      on the 0-msec condition (86%) than on the 50-msec condition (68%); there were a
      minority number of words on which the results were just the opposite. A second
      study using the same interruption paradigm but 300 different words reported
      similar relations, with 63% correct recognition on the 0-msec condition and 48%
      on the 50-msec condition (Wilson and Irish, 2015). Both studies suggest the
      importance that the first 50 msec of the target word has on intelligibility.
      PURPOSE: To define in detail the effects that interruption patterns have on word
      recognition as the interruption pattern was incremented with reference to word
      onset from 0 to 90 msec in 10-msec steps. RESEARCH DESIGN: A repeated-measures
      design with ten interruption patterns (onset conditions). STUDY SAMPLE: Twenty
      four young listeners (19-29 yr) with normal hearing for pure tones participated
      in this study. DATA COLLECTION AND ANALYSES: Seventy consonant-nucleus-consonant
      words formed the corpus of materials with 25 additional words used for practice.
      For each participant, the 700 stimuli (70 words by ten onset conditions) were
      interrupted (10 interruptions/sec; 50% duty cycle), randomized, and recorded on
      compact disc in 28, 25-word tracks. RESULTS: The overall mean recognition
      performance was 80.4% with mean performances for the ten conditions ranging from
      73.0% (50-msec condition) to 87.7% (90-msec condition). The mean recognition
      performances changed systematically, decreasing from the 0-msec condition to the
      50-msec condition and then increasing to the 90-msec condition, which formed a U
      shaped function of the means. Of the 45 mean paired comparisons (post hoc t-tests
      with Bonferroni corrections), there were 17 significant differences at the p <=
      0.001 level, increasing to 31 significant differences when the significance level
      was increased to the p <= 0.01 level. Visual inspection of the 70-word
      performance functions revealed that 32 words had flat functions, 34 words had U
      shaped functions, two functions were rising, one was an inverted V-shape, and one
      was irregular. CONCLUSIONS: First, some words (utterances of those words) were
      immune to any differential effects of the ten interruption patterns. These words
      with flat performance functions constituted 46% of the word corpus. Second, 49%
      of the words exhibited U-shaped performance functions that were always
      systematic, going from maximum to minimum and back to maximum. These words were
      thought to be more dependent on the initial consonant to attain maximum
      performance. The conclusion is that some words are not affected by the location
      of the interruption pattern (those with flat functions) whereas other words are
      substantially affected (those with U-shaped functions).

PMID- 26218057
TI  - JAAA CEU Program (A).

PMID- 26218058
TI  - JAAA CEU Program (B).

PMID- 26218056
TI  - Response to: "All treatments in tinnitus are Experimental, Controversial and
      Futuristic" by De Ridder et al (2015).

PMID- 26218059
TI  - Structure and Reactivity of Indolylmethylium Ions: Scope and Limitations in
      Synthetic Applications.
AB  - Eight substituted aryl(indol-3-yl)methylium tetrafluoroborates 3(a-h)-BF4 and
      three bis(indol-3-yl)methylium tetrafluoroborates 3(i-k)-BF4 have been
      synthesized and characterized by NMR spectroscopy and X-ray crystallography.
      Their reactions with pi-nucleophiles 8(a-j) (silylated enol ethers and ketene
      acetals) were studied kinetically using photometric monitoring at 20  degrees C.
      The resulting second-order rate constants were found to follow the correlation
      log k(20  degrees C) = sN(N + E), in which nucleophiles are characterized by the
      two solvent-dependent parameters N and sN, and electrophiles are characterized by
      one parameter, E. From the previously reported N and sN parameters of the
      employed nucleophiles and the measured rate constants, the electrophilicities of
      the indol-3-ylmethylium ions 3(a-k) were derived and used to predict potential
      nucleophilic reaction partners. A discrepancy between published rate constants
      for the reactions of morpholine and piperidine with the (2-methylindol-3
      yl)phenylmethylium ion 3h and those calculated from E, N, and sN was analyzed and
      demonstrated to be due to a mistake of the value reported in the literature. 

PMID- 26218060
TI  - Multimodal heart beat detection using signal quality indices.
AB  - The electrocardiogram (ECG) is a well studied signal from which many clinically
      relevant parameters can be derived, such as heart rate. A key component in the
      estimation of these parameters is the accurate detection of the R peak in the QRS
      complex. While corruption of the ECG by movement artefact or sensor failure can
      result in poor delineation of the R peak, use of synchronously measured signals
      could allow for resolution of the R peak even scenarios with poor quality ECG
      recordings. Robust estimation of R peak locations from multimodal signals
      facilitates real time monitoring and is likely to reduce false alarms due to
      inaccurate derived parameters.We propose a method which fuses R peaks detected on
      the ECG using an energy detector with those detected on the arterial blood
      pressure (ABP) waveform using the length transform. A signal quality index (SQI)
      for the two signals is then derived. The ECG SQI is based upon the agreement
      between two distinct peak detectors. The ABP SQI estimates the blood pressure at
      various phases in the cardiac cycle and only accepts the signal as good quality
      if the values are physiologically plausible. Detections from these two signals
      were merged by selecting the R peak detections from the signal with a higher SQI.
      The approach presented in this paper was evaluated on datasets provided for the
      Physionet/Computing in Cardiology Challenge 2014. The algorithm achieved a
      sensitivity of 95.1% and positive predictive value of 89.3% on an external
      evaluation set, and achieved a score of 91.5%.The method here demonstrated
      excellent performance across a variety of signal morphologies collected during
      clinical practice. Fusion of R peaks from other signals has the potential to
      provide informed estimates of the R peak location in situations where the ECG is
      noisy or completely absent. Source code for the algorithm is made available
      freely online. 

PMID- 26218061
TI  - Cloning, expression, and polymorphism at the 5'-flanking region of the GnRH gene
      and their association with laying traits in Muscovy duck (Cairina moschata).
AB  - Gonadotropin-releasing hormone (GnRH), a neuropeptide, plays a vital role in the
      hypothalamus-pituitary-gonadal (HPG) axis. In vertebrates, GnRH is crucial for
      the onset of sexual development and the entire reproductive process. The purpose
      of this study was to identify genetic factors associated with egg-laying traits
      of Muscovy ducks. The full-length cDNA (474 bp) of Muscovy duck GnRH was obtained
      and characterised. It encodes 92 amino acids containing a 1-amino acid signal
      peptide cleavage site. Phylogenetic analysis revealed that Muscovy duck GnRH has
      a close relationship with Anas platyrhynchos GnRH. GnRH showed significantly
      different expression profiles between 4 developmental periods in the
      hypothalamus, pituitary, and ovary. The expression of GnRH in the laying period
      (36 weeks) was higher than at other periods in the three tissues. GnRH was widely
      expressed in 12 examined tissues of nesting and laying Muscovy ducks. In the
      hypothalamus, pituitary and gonads, the expression of GnRH was higher than in
      other tissues. In laying Muscovy ducks, the expression of GnRH in the
      hypothalamus, pituitary, ovary, muscular stomach, pancreas, heart, duodenum and
      spleen was significantly higher than in nesting dusks. Differences were detected
      in the liver and glandular stomach between laying ducks and nesting ducks.
      Differences between the kidney and lung were not significant. In the pituitary,
      the GnRH and GnRH receptor (GnRHR) genes shared the same expression profiles
      during 4 time points. Both genes had the highest expression at 36 weeks of age. A
      mutation (g.206G > A) in the 5'-flanking region was associated with egg-laying
      performance. Individuals with genotype GG had better egg-laying performance than
      the individuals with genotype AA. GnRH may be used as a marker gene for laying
      performance in the Muscovy duck. 

PMID- 26218063
TI  - Chromophore Deprotonation State Alters the Optical Properties of Blue
      Chromoprotein.
AB  - Chromoproteins (CPs) have unique colors and can be used in biological
      applications. In this work, a novel blue CP with a maximum absorption peak
      (lambdamax) at 608 nm was identified from the carpet anemone Stichodactyla
      gigantea (sgBP). In vivo expression of sgBP in zebrafish would change the
      appearance of the fishes to have a blue color, indicating the potential biomarker
      function. To enhance the color properties, the crystal structure of sgBP at 2.25
      A resolution was determined to allow structure-based protein engineering. Among
      the mutations conducted in the Gln-Tyr-Gly chromophore and chromophore
      environment, a S157C mutation shifted the lambdamax to 604 nm with an extinction
      coefficient (epsilon) of 58,029 M-1.cm-1 and darkened the blue color expression.
      The S157C mutation in the sgBP chromophore environment could affect the color
      expression by altering the deprotonation state of the phenolic group in the
      chromophore. Our results provide a structural basis for the blue color
      enhancement of the biomarker development. 

PMID- 26218064
TI  - Modification of Gene Expression, Proliferation, and Function of OP9 Stroma Cells
      by Bcr-Abl-Expressing Leukemia Cells.
AB  - Expression of the Bcr-Abl fusion gene in hematopoietic progenitor cells (HPCs)
      results in the development of chronic myelogenous leukemia (CML), for which
      hematopoietic microenvironment plays an important role. We investigated the
      specific effects of an HPC line transduced with Bcr-Abl, KOBA, on BM-derived OP9
      stroma cells. DNA microarray analysis revealed that OP9 cells co-cultured with
      KOBA cells (OP9/L) show diverse changes in the gene expression. OP9/L cells
      showed significant down-regulation of Cdkn genes and up-regulation of Icam1,
      leading to the increased proliferation capacity of OP9 cells and enhanced
      transmigration of leukemia cells through them. The effects were attributed to
      direct Notch activation of OP9 cells by KOBA cells. OP9/L cells also showed a
      markedly altered cytokine gene expression pattern, including a robust increase in
      a variety of proinflammatory genes and a decrease in hematopoietic cytokines such
      as Cxcl12, Scf, and Angpt1. Consequently, OP9/L cells promoted the proliferation
      of KOBA cells more efficiently than parental OP9 cells, whereas the activity
      supporting normal myelopoiesis was attenuated. In mice bearing KOBA leukemia, the
      characteristic genetic changes observed in OP9/L cells were reflected
      differentially in the endothelial cells (ECs) and mesenchymal stroma cells (MCs)
      of the BM. The ECs were markedly increased with Notch-target gene activation and
      decreased Cdkn expression, whereas the MCs showed a marked increase in
      proinflammatory gene expression and a profound decrease in hematopoietic genes.
      Human CML cell lines also induced essentially similar genetic changes in OP9
      cells. Our results suggest that CML cells remodel the hematopoietic
      microenvironment by changing the gene expression patterns differentially in ECs
      and MCs of BM. 

PMID- 26218065
TI  - Perceptions of Community Members and Healthcare Workers on Male Involvement in
      Prevention of Mother-To-Child Transmission Services in Khayelitsha, Cape Town,
      South Africa.
AB  - Involving male partners of pregnant women accessing PMTCT programs has the
      potential to improve health outcomes for women and children. This study explored
      community members' (men and women) and healthcare workers' perceptions of male
      involvement in the prevention of mother-to-child transmission of HIV in
      Khayelitsha, South Africa. Two focus group discussions were held with 25 men of
      unknown HIV status and one focus group discussion held with 12 HIV-positive women
      in the community. In depth interviews were conducted with four HIV-positive
      couples and five service providers purposely sampled from the community and a
      health facility, respectively. Both men and women interviewed in this study were
      receptive towards male involvement in PMTCT. However, men were reluctant to
      engage with health services due to stigma and negative attitudes from nurses.
      This study also found HIV testing, disclosure and direct health worker engagement
      with men increases male involvement in PMTCT. Using men in the media and
      community to reach out to fellow men with prevention messages tailored to suit
      specific audiences may reduce perceptions of antenatal care as being a woman's
      domain. 

PMID- 26218066
TI  - Mesopic Functional Visual Acuity in Normal Subjects.
AB  - To evaluate mesopic functional visual acuity (FVA) with a newly developed system
      in normal subjects and to compare the results with photopic FVA, sixty-eight
      healthy volunteers (24.03 +/- 4.42 [mean +/- standard deviation] years) were
      enrolled in this study. A commercially available FVA measurement system (AS-28;
      Kowa, Aichi, Japan) was modified to measure FVA under mesopic conditions as well
      as photopic conditions. Measurements were performed monocularly in photopic
      conditions during 60 seconds. After dark adaptation for 15 minutes, the same
      measurements were repeated in mesopic conditions. Outcomes included starting
      visual acuity (VA), FVA (the average of VAs), visual maintenance ratio (VMR),
      maximum VA, minimum VA, and numbers of blinks during the 60-second measurement
      session, and were compared between mesopic and photopic conditions. Starting VA
      was -0.11 +/- 0.08 and 0.39 +/- 0.12 logarithm of the minimum angle of resolution
      (logMAR) in photopic and mesopic conditions, respectively. FVA was -0.06 +/- 0.09
      and 0.52 +/- 0.14 logMAR, VMR was 0.98 +/- 0.02 and 0.94 +/- 0.04, maximum VA was
      -0.15 +/- 0.06 and 0.33 +/- 0.12 logMAR, the minimum VA was 0.05 +/- 0.12 and
      0.78 +/- 0.20 logMAR, and the number of blinks was 8.23 +/- 7.54 and 7.23 +/-
      6.20, respectively. All these parameters except the number of blinks were
      significantly different between the two conditions (P < 0.001). Besides, the
      difference between maximum and minimum VAs and standard deviation of VA were
      significantly larger in mesopic than in photopic conditions (P < 0.001). This
      study revealed that not only overall visual function decline but also instability
      of vision under mesopic conditions even in healthy subjects. 

PMID- 26218067
TI  - Oral Administration of P. gingivalis Induces Dysbiosis of Gut Microbiota and
      Impaired Barrier Function Leading to Dissemination of Enterobacteria to the
      Liver.
AB  - Although periodontitis has been implicated as a risk factor for various systemic
      diseases, the precise mechanisms by which periodontitis induces systemic disease
      remain to be elucidated. We have previously revealed that repeated oral
      administration of Porphyromonas gingivalis elicits endotoxemia via changes in the
      gut microbiota of the ileum, and thereby induces systemic inflammation and
      insulin resistance. However, it is not clear to what extent a single
      administration of P. gingivalis could affect gut microbiota composition, gut
      barrier function, and subsequent influx of gut microbiota into the liver.
      Therefore, in the present study, C57BL/6 mice were orally administered P.
      gingivalis (strain W83) once and compared to sham-inoculated mice. The
      phylogenetic structure and diversity of microbial communities in the gut and
      liver were analyzed by pyrosequencing the 16S ribosomal RNA genes. Serum
      endotoxin activity was determined by a Limulus amebocyte lysate test. Gene
      expression in the intestine and expression of 16S rRNA genes in the blood and
      liver were examined by quantitative polymerase chain reaction. Administration of
      P. gingivalis significantly altered gut microbiota, with an increased proportion
      of phylum Bacteroidetes, a decreased proportion of phylum Firmicutes, and
      increased serum endotoxin levels. In the intestinal tissues, gene expression of
      tjp-1 and occludin, which are involved in intestinal permeability, were
      downregulated. Higher amounts of bacterial DNA were detected in the liver of
      infected mice. Importantly, changes in gut microbiota preceded systemic
      inflammatory changes. These results further support the idea that disturbance of
      the gut microbiota composition by orally derived periodontopathic bacteria may be
      a causal mechanism linking periodontitis and systemic disease. 

PMID- 26218068
TI  - Metachronous Second Primary Malignancies after Head and Neck Cancer in a Korean
      Cohort (1993-2010).
AB  - Second primary malignancy (SPM) is the major long-term cause of patient mortality
      with head and neck squamous cell carcinoma (HNSCC). As the incidence of high-risk
      human papillomavirus (HPV)-related HNSCC is increasing globally, we analyzed the
      patterns of SPM occurrence, the effect of the index tumor site along with
      attributes to HPV, and the effect of SPM on survival in South Korean patients
      with head and neck cancer (HNC). Data were retrieved from the Korea Central
      Cancer Registry, a nationwide population-based cancer registry, from 1993 to
      2010. Standardized incidence ratios were analyzed and compared between index
      tumor sites, particularly oropharyngeal vs. non-oropharyngeal sites. After
      adjustment for competing risks, 3- and 5-year SPM rates were calculated using the
      cumulative incidence function. The effects of SPM occurrence on overall survival
      (OS) were then analyzed. SPM rates were significantly lower for HPV-attributable
      oropharyngeal sites than for non-oropharyngeal sites, such as the larynx and
      hypopharynx (p<0.001). SPM rates were also lower for oral cavity first primary
      sites than for non-oropharyngeal first primary sites (p<0.001). SPMs typically
      occurred in the esophagus, lungs and the head and neck. Uterine cervical cancers
      occurred significantly more frequently after index oropharyngeal cancer in women.
      The 5-year and 10-year OS rates were 57.8 and 45.7% in all HNC patients,
      respectively. The OS after SPM occurrence was poor (5-year, 31.8%; 10-year,
      20.8%) compared to after index HNC occurrence (5-year, 68.4%; 10-year, 41.2%).
      SPM occurrence in the esophagus and lung/bronchus showed a worse OS than SPM
      localized to the head and neck. South Korean HNC patient, the first primary
      cancer site affected SPM risk and distribution. The 5- and 10-year OS rates
      deteriorated after SPM occurrence, particularly in the esophagus and lungs.
      Further optimization of follow-up strategies for effective surveillance of SPM,
      particularly in the esophagus and lungs, is warranted. 

PMID- 26218069
TI  - Failure to Target RANKL Signaling Through p38-MAPK Results in Defective
      Osteoclastogenesis in the Microphthalmia Cloudy-Eyed Mutant.
AB  - The Microphthalmia-associated transcription factor (MITF) is a basic helix-loop
      helix leucine zipper family factor that is essential for terminal osteoclast
      differentiation. Previous work demonstrates that phosphorylation of MITF by p38
      MAPK downstream of Receptor Activator of NFkB Ligand (RANKL) signaling is
      necessary for MITF activation in osteoclasts. The spontaneous Mitf cloudy eyed
      (ce) allele results in production of a truncated MITF protein that lacks the
      leucine zipper and C-terminal end. Here we show that the Mitf(ce) allele leads to
      a dense bone phenotype in neonatal mice due to defective osteoclast
      differentiation. In response to RANKL stimulation, in vitro osteoclast
      differentiation was impaired in myeloid precursors derived from neonatal or adult
      Mitf(ce/ce) mice. The loss of the leucine zipper domain in Mitf(ce/ce) mice does
      not interfere with the recruitment of MITF/PU.1 complexes to target promoters.
      Further, we have mapped the p38 MAPK docking site within the region deleted in
      Mitf(ce). This interaction is necessary for the phosphorylation of MITF by p38
      MAPK. Site-directed mutations in the docking site interfered with the interaction
      between MITF and its co-factors FUS and BRG1. MITF-ce fails to recruit FUS and
      BRG1 to target genes, resulting in decreased expression of target genes and
      impaired osteoclast function. These results highlight the crucial role of
      signaling dependent MITF/p38 MAPK interactions in osteoclast differentiation.

PMID- 26218071
TI  - Correction: Chronic Hepatitis B Virus Infection: The Relation between Hepatitis B
      Antigen Expression, Telomere Length, Senescence, Inflammation and Fibrosis.

PMID- 26218070
TI  - Crystal Structure of a Thermostable Alanine Racemase from Thermoanaerobacter
      tengcongensis MB4 Reveals the Role of Gln360 in Substrate Selection.
AB  - Pyridoxal 5'-phosphate (PLP) dependent alanine racemase catalyzes racemization of
      L-Ala to D-Ala, a key component of the peptidoglycan network in bacterial cell
      wall. It has been extensively studied as an important antimicrobial drug target
      due to its restriction in eukaryotes. However, many marketed alanine racemase
      inhibitors also act on eukaryotic PLP-dependent enzymes and cause side effects. A
      thermostable alanine racemase (AlrTt) from Thermoanaerobacter tengcongensis MB4
      contains an evolutionarily non-conserved residue Gln360 in inner layer of the
      substrate entryway, which is supposed to be a key determinant in substrate
      specificity. Here we determined the crystal structure of AlrTt in complex with L
      Ala at 2.7 A resolution, and investigated the role of Gln360 by saturation
      mutagenesis and kinetic analysis. Compared to typical bacterial alanine racemase,
      presence of Gln360 and conformational changes of active site residues disrupted
      the hydrogen bonding interactions necessary for proper PLP immobilization, and
      decreased both the substrate affinity and turnover number of AlrTt. However, it
      could be complemented by introduction of hydrophobic amino acids at Gln360,
      through steric blocking and interactions with a hydrophobic patch near active
      site pocket. These observations explained the low racemase activity of AlrTt,
      revealed the essential role of Gln360 in substrate selection, and its preference
      for hydrophobic amino acids especially Tyr in bacterial alanine racemization. Our
      work will contribute new insights into the alanine racemization mechanism for
      antimicrobial drug development. 

PMID- 26218072
TI  - Low Pressure CO2 Hydrogenation to Methanol over Gold Nanoparticles Activated on a
      CeO(x)/TiO2 Interface.
AB  - Capture and recycling of CO2 into valuable chemicals such as alcohols could help
      mitigate its emissions into the atmosphere. Due to its inert nature, the
      activation of CO2 is a critical step in improving the overall reaction kinetics
      during its chemical conversion. Although pure gold is an inert noble metal and
      cannot catalyze hydrogenation reactions, it can be activated when deposited as
      nanoparticles on the appropriate oxide support. In this combined experimental and
      theoretical study, it is shown that an electronic polarization at the metal-oxide
      interface of Au nanoparticles anchored and stabilized on a CeO(x)/TiO2 substrate
      generates active centers for CO2 adsorption and its low pressure hydrogenation,
      leading to a higher selectivity toward methanol. This study illustrates the
      importance of localized electronic properties and structure in catalysis for
      achieving higher alcohol selectivity from CO2 hydrogenation.

PMID- 26218074
TI  - The Health Extension Program and Its Association with Change in Utilization of
      Selected Maternal Health Services in Tigray Region, Ethiopia: A Segmented Linear
      Regression Analysis.
AB  - BACKGROUND: In 2003, the Ethiopian Ministry of Health established the Health
      Extension Program (HEP), with the goal of improving access to health care and
      health promotion activities in rural areas of the country. This paper aims to
      assess the association of the HEP with improved utilization of maternal health
      services in Northern Ethiopia using institution-based retrospective data.
      METHODS: Average quarterly total attendances for antenatal care (ANC), delivery
      care (DC) and post-natal care (PNC) at health posts and health care centres were
      studied from 2002 to 2012. Regression analysis was applied to two models to
      assess whether trends were statistically significant. One model was used to
      estimate the level and trend changes associated with the immediate period of
      intervention, while changes related to the post-intervention period were
      estimated by the other. RESULTS: The total number of consultations for ANC, DC
      and PNC increased constantly, particularly after the late-intervention period.
      Increases were higher for ANC and PNC at health post level and for DC at health
      centres. A positive statistically significant upward trend was found for DC and
      PNC in all facilities (p<0.01). The positive trend was also present in ANC at
      health centres (p = 0.04), but not at health posts. CONCLUSION: Our findings
      revealed an increase in the use of antenatal, delivery and post-natal care after
      the introduction of the HEP. We are aware that other factors, that we could not
      control for, might be explaining that increase. The figures for DC and PNC are
      however low and more needs to be done in order to increase the access to the
      health care system as well as the demand for these services by the population.
      Strengthening of the health information system in the region needs also to be
      prioritized.

PMID- 26218073
TI  - Nullspace Sampling with Holonomic Constraints Reveals Molecular Mechanisms of
      Protein Galphas.
AB  - Proteins perform their function or interact with partners by exchanging between
      conformational substates on a wide range of spatiotemporal scales. Structurally
      characterizing these exchanges is challenging, both experimentally and
      computationally. Large, diffusional motions are often on timescales that are
      difficult to access with molecular dynamics simulations, especially for large
      proteins and their complexes. The low frequency modes of normal mode analysis
      (NMA) report on molecular fluctuations associated with biological activity.
      However, NMA is limited to a second order expansion about a minimum of the
      potential energy function, which limits opportunities to observe diffusional
      motions. By contrast, kino-geometric conformational sampling (KGS) permits large
      perturbations while maintaining the exact geometry of explicit conformational
      constraints, such as hydrogen bonds. Here, we extend KGS and show that a
      conformational ensemble of the alpha subunit Galphas of heterotrimeric
      stimulatory protein Gs exhibits structural features implicated in its activation
      pathway. Activation of protein Gs by G protein-coupled receptors (GPCRs) is
      associated with GDP release and large conformational changes of its alpha-helical
      domain. Our method reveals a coupled alpha-helical domain opening motion while,
      simultaneously, Galphas helix alpha5 samples an activated conformation. These
      motions are moderated in the activated state. The motion centers on a dynamic hub
      near the nucleotide-binding site of Galphas, and radiates to helix alpha4. We
      find that comparative NMA-based ensembles underestimate the amplitudes of the
      motion. Additionally, the ensembles fall short in predicting the accepted
      direction of the full activation pathway. Taken together, our findings suggest
      that nullspace sampling with explicit, holonomic constraints yields ensembles
      that illuminate molecular mechanisms involved in GDP release and protein Gs
      activation, and further establish conformational coupling between key structural
      elements of Galphas. 

PMID- 26218075
TI  - Characterization of Antibiotic Resistance Gene Abundance and Microbiota
      Composition in Feces of Organic and Conventional Pigs from Four EU Countries.
AB  - One of the recent trends in animal production is the revival of interest in
      organic farming. The increased consumer interest in organic animal farming is
      mainly due to concerns about animal welfare and the use of antibiotics in
      conventional farming. On the other hand, providing animals with a more natural
      lifestyle implies their increased exposure to environmental sources of different
      microorganisms including pathogens. To address these concerns, we determined the
      abundance of antibiotic resistance and diversity within fecal microbiota in pigs
      kept under conventional and organic farming systems in Sweden, Denmark, France
      and Italy. The abundance of sul1, sul2, strA, tet(A), tet(B) and cat antibiotic
      resistance genes was determined in 468 samples by real-time PCR and the fecal
      microbiota diversity was characterized in 48 selected samples by pyrosequencing
      of V3/V4 regions of 16S rRNA. Contrary to our expectations, there were no
      extensive differences between the abundance of tested antibiotic resistance genes
      in microbiota originating from organic or conventionally housed pigs within
      individual countries. There were also no differences in the microbiota
      composition of organic and conventional pigs. The only significant difference was
      the difference in the abundance of antibiotic resistance genes in the samples
      from different countries. Fecal microbiota in the samples originating from
      southern European countries (Italy, France) exhibited significantly higher
      antibiotic resistance gene abundance than those from northern parts of Europe
      (Denmark, Sweden). Therefore, the geographical location of the herd influenced
      the antibiotic resistance in the fecal microbiota more than farm's status as
      organic or conventional. 

PMID- 26218077
TI  - Treatment with 5-Azacytidine improves clinical outcome in high-risk MDS patients
      in the 'real life' setting: A single center observational study.
AB  - OBJECTIVES: The demethylating factor 5-Azacytidine (5-AZA) improves survival of
      patients with myelodysplastic syndromes (MDS) in randomized control trials but
      the results in 'real life' are controversial. METHODS: In this retrospective
      study, we evaluated the outcome of 56 high-risk MDS patients who were treated
      with 5-AZA between 2005 and 2013. 5-AZA was administered in an outpatient basis
      at a dose 75 mg/m(2) s.c. with the following schedule: 5 days on/weekend off/2
      days on (5/2/2). RESULTS: The overall response rate (ORR) was 50%; 21.2% patients
      achieved complete response (CR), 3.8% partial response (PR), and 25% hematologic
      improvement (HI); 34.6% had stable disease (SD) and 15.4% showed progressive
      disease (PD). The estimated median event free survival (EFS) and overall survival
      (OS) were 11 and 17 months, respectively. Interestingly, the estimated time to
      acute myeloid leukemia transformation was 30 months, which refers to patients who
      responded to AZA treatment or remained stable. Patients who responded to the 5
      AZA achieving CR, PR, and HI had better EFS and OS compared to the patients who
      had SD or PD. In addition, Delta WHO Classification-based Prognostic Score System
      (DeltaWPSS), which represents the improvement of WPSS risk group before and after
      treatment, was associated with significantly improved OS and better EFS. Finally,
      the response to treatment was not associated with the expression of p53.
      CONCLUSIONS: In conclusion, 5-AZA is an effective treatment for high-risk MDS.
      Improved OS and EFS were found mainly in patients who responded to the treatment
      while DeltaWPSS seems to represent a promising future prognostic tool.

PMID- 26218076
TI  - Planar Covariation of Hindlimb and Forelimb Elevation Angles during Terrestrial
      and Aquatic Locomotion of Dogs.
AB  - The rich repertoire of locomotor behaviors in quadrupedal animals requires
      flexible inter-limb and inter-segmental coordination. Here we studied the
      kinematic coordination of different gaits (walk, trot, gallop, and swim) of six
      dogs (Canis lupus familiaris) and, in particular, the planar covariation of limb
      segment elevation angles. The results showed significant variations in the
      relative duration of rearward limb movement, amplitude of angular motion, and
      inter-limb coordination, with gait patterns ranging from a lateral sequence of
      footfalls during walking to a diagonal sequence in swimming. Despite these
      differences, the planar law of inter-segmental coordination was maintained across
      different gaits in both forelimbs and hindlimbs. Notably, phase relationships and
      orientation of the covariation plane were highly limb specific, consistent with
      the functional differences in their neural control. Factor analysis of published
      muscle activity data also demonstrated differences in the characteristic timing
      of basic activation patterns of the forelimbs and hindlimbs. Overall, the results
      demonstrate that the planar covariation of inter-segmental coordination has
      emerged for both fore- and hindlimbs and all gaits, although in a limb-specific
      manner. 

PMID- 26218078
TI  - The Energy of COPI for Budding Membranes.
AB  - As a major actor of cellular trafficking, COPI coat proteins assemble on
      membranes and locally bend them to bud 60 nm-size coated particles. Budding
      requires the energy of the coat assembly to overcome the one necessary to deform
      the membrane which primarily depends on the bending modulus and surface tension,
      gamma. Using a COPI-induced oil nanodroplet formation approach, we modulated the
      budding of nanodroplets using various amounts and types of surfactant. We found a
      Heaviside-like dependence between the budding efficiency and gamma: budding was
      only dependent on gamma and occurred beneath 1.3 mN/m. With the sole contribution
      of gamma to the membrane deformation energy, we assessed that COPI supplies ~1500
      kBT for budding particles from membranes, which is consistent with common
      membrane deformation energies. Our results highlight how a simple remodeling of
      the composition of membranes could mechanically modulate budding in cells. 

PMID- 26218094
TI  - Synthesis and Thorough Investigation of Discrete Organotin Telluride Clusters.
AB  - Systematic experimental and theoretical investigations of reactions of R(1)SnCl3
      (R(1) = CMe2CH2C(Me)O) with (Me3Si)2Te allowed for the stepwise formation and
      single-crystalline isolation of the first tin sesquitelluride clusters with
      functional organic ligands. Subsequent derivatization of the latter took place
      under reorganization of the inorganic core, affording clusters with complex
      hybrid architectures.

PMID- 26218095
TI  - Aerial Prefeeding Followed by Ground Based Toxic Baiting for More Efficient and
      Acceptable Poisoning of Invasive Small Mammalian Pests.
AB  - Introduced brushtail possums (Trichosurus vulpecula) and rat species (Rattus
      spp.) are major vertebrate pests in New Zealand, with impacts on conservation and
      agriculture being managed largely through poisoning operations. Aerial
      distribution of baits containing sodium fluoroacetate (1080) has been refined to
      maximise cost effectiveness and minimise environmental impact, but this method is
      strongly opposed by some as it is perceived as being indiscriminate. Although
      ground based control enables precise placement of baits, operations are often
      more than twice as costly as aerial control, mainly due to the high labour costs.
      We investigated a new approach to ground based control that combined aerial
      distribution of non-toxic 'prefeed' baits followed by sparse distribution of
      toxic baits at regular intervals along the GPS tracked prefeeding flight paths.
      This approach was tested in two field trials in which both 1080 baits and
      cholecalciferol baits were used in separate areas. Effectiveness of the approach,
      assessed primarily using 'chewcards', was compared with that of scheduled aerial
      1080 operations that were conducted in outlying areas of both trials. Contractors
      carrying out ground based control were able to follow the GPS tracks of aerial
      prefeeding flight lines very accurately, and with 1080 baits achieved very high
      levels of kill of possums and rats similar to those achieved by aerial 1080
      baiting. Cholecalciferol was less effective in the first trial, but by doubling
      the amount of cholecalciferol bait used in the second trial, few possums or rats
      survived. By measuring the time taken to complete ground baiting from GPS tracks,
      we predicted that the method (using 1080 baits) would be similarly cost effective
      to aerial 1080 operations for controlling possums and rats, and considerably less
      expensive than typical current costs of ground based control. The main
      limitations to the use of the method will be access to, and size of, the
      operational site, along with topography and vegetation density. 

PMID- 26218081
TI  - Comparison of stimulus-evoked cerebral hemodynamics in the awake mouse and under
      a novel anesthetic regime.
AB  - Neural activity is closely followed by a localised change in cerebral blood flow,
      a process termed neurovascular coupling. These hemodynamic changes form the basis
      of contrast in functional magnetic resonance imaging (fMRI) and are used as a
      correlate for neural activity. Anesthesia is widely employed in animal fMRI and
      neurovascular studies, however anesthetics are known to profoundly affect neural
      and vascular physiology, particularly in mice. Therefore, we investigated the
      efficacy of a novel 'modular' anesthesia that combined injectable (fentanyl
      fluanisone/midazolam) and volatile (isoflurane) anesthetics in mice. To
      characterize sensory-evoked cortical hemodynamic responses, we used optical
      imaging spectroscopy to produce functional maps of changes in tissue oxygenation
      and blood volume in response to mechanical whisker stimulation. Following fine
      tuning of the anesthetic regime, stimulation elicited large and robust
      hemodynamic responses in the somatosensory cortex, characterized by fast arterial
      activation, increases in total and oxygenated hemoglobin, and decreases in
      deoxygenated hemoglobin. Overall, the magnitude and speed of evoked hemodynamic
      responses under anesthesia resembled those in the awake state, indicating that
      the novel anesthetic combination significantly minimizes the impact of
      anesthesia. Our findings have broad implications for both neurovascular research
      and longitudinal fMRI studies that increasingly require the use of genetically
      engineered mice. 

PMID- 26218096
TI  - Phytoplankton Productivity in an Arctic Fjord (West Greenland): Estimating
      Electron Requirements for Carbon Fixation and Oxygen Production.
AB  - Accurate quantification of pelagic primary production is essential for
      quantifying the marine carbon turnover and the energy supply to the food web.
      Knowing the electron requirement (Kappa) for carbon (C) fixation (KappaC) and
      oxygen (O2) production (KappaO2), variable fluorescence has the potential to
      quantify primary production in microalgae, and hereby increasing spatial and
      temporal resolution of measurements compared to traditional methods. Here we
      quantify KappaC and KappaO2 through measures of Pulse Amplitude Modulated (PAM)
      fluorometry, C fixation and O2 production in an Arctic fjord (Godthabsfjorden, W
      Greenland). Through short- (2h) and long-term (24h) experiments, rates of
      electron transfer (ETRPSII), C fixation and/or O2 production were quantified and
      compared. Absolute rates of ETR were derived by accounting for Photosystem II
      light absorption and spectral light composition. Two-hour incubations revealed a
      linear relationship between ETRPSII and gross 14C fixation (R2 = 0.81) during
      light-limited photosynthesis, giving a KappaC of 7.6 +/- 0.6 (mean +/- S.E.) mol
      e (mol C)-1. Diel net rates also demonstrated a linear relationship between
      ETRPSII and C fixation giving a KappaC of 11.2 +/- 1.3 mol e (mol C)-1 (R2 =
      0.86). For net O2 production the electron requirement was lower than for net C
      fixation giving 6.5 +/- 0.9 mol e (mol O2)-1 (R2 = 0.94). This, however, still is
      an electron requirement 1.6 times higher than the theoretical minimum for O2
      production [i.e. 4 mol e (mol O2)-1]. The discrepancy is explained by respiratory
      activity and non-photochemical electron requirements and the variability is
      discussed. In conclusion, the bio-optical method and derived electron requirement
      support conversion of ETR to units of C or O2, paving the road for improved
      spatial and temporal resolution of primary production estimates. 

PMID- 26218098
TI  - Effects of Nitrogen Doping on X-band Dielectric Properties of Carbon
      Nanotube/Polymer Nanocomposites.
AB  - Nitrogen-doped and undoped carbon nanotubes (CNTs) were synthesized by selective
      passing of source and carrier gases (ethane, ammonia, hydrogen, and argon) over
      an alumina-supported iron catalyst in a quartz tubular reactor at 650  degrees C.
      Synthesized CNTs were mixed with polyvinylidene fluoride with an Alberta polymer
      asymmetric minimixer (APAM) mixer at 240  degrees C and 235 rpm, and the
      resulting nanocomposites were compression molded. Transmission electron
      microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and
      thermogravimetric analysis (TGA) techniques revealed that introducing nitrogen
      into the crystalline structure of CNTs resulted in higher crystalline defects.
      Dielectric measurements showed that nitrogen doping significantly increased
      dielectric permittivity for a known dielectric loss. This was ascribed to the
      role of the crystalline defects and nitrogen atoms, which acted as polarizing
      centers, blocked the nomadic charges, polarized them, and prevented them from
      moving along CNTs. The obtained results introduce nitrogen doping as a regulative
      tool to control the dielectric properties of CNT/polymer nanocomposites. 

PMID- 26218097
TI  - One of Three Pex11 Family Members Is Required for Peroxisomal Proliferation and
      Full Virulence of the Rice Blast Fungus Magnaporthe oryzae.
AB  - Peroxisomes play important roles in metabolisms of eukaryotes and infection of
      plant fungal pathogens. These organelles proliferate by de novo formation or
      division in response to environmental stimulation. Although the assembly of
      peroxisomes was documented in fungal pathogens, their division and its
      relationship to pathogenicity remain obscure. In present work, we analyzed the
      roles of three Pex11 family members in peroxisomal division and pathogenicity of
      the rice blast fungus Magnaporthe oryzae. Deletion of MoPEX11A led to fewer but
      enlarged peroxisomes, and impaired the separation of Woronin bodies from
      peroxisomes, while deletion of MoPEX11B or MoPEX11C put no evident impacts to
      peroxisomal profiles. MoPEX11A mutant exhibited typical peroxisome related
      defects, delayed conidial germination and appressoria formation, and decreased
      appressorial turgor and host penetration. As a result, the virulence of MoPEX11A
      mutant was greatly reduced. Deletion of MoPEX11B and MoPEX11C did not alter the
      virulence of the fungus. Further, double or triple deletions of the three genes
      were unable to enhance the virulence decrease in MoPEX11A mutant. Our data
      indicated that MoPEX11A is the main factor modulating peroxisomal division and is
      required for full virulence of the fungus. 

PMID- 26218099
TI  - The Sensitivity of Differential Ratings of Perceived Exertion as Measures of
      Internal Load.
AB  - PURPOSE: To investigate the sensitivity of differential ratings of perceived
      exertion (dRPE) as measures of internal load. METHODS: Twenty-two male university
      soccer players performed 2 maximal incremental-exercise protocols (cycle,
      treadmill) on separate days. Maximal oxygen uptake (VO2max), maximal heart rate
      (HRmax), peak blood lactate concentration (B[La]peak), and the preprotocol-to
      postprotocol change in countermovement-jump height (DeltaCMJH) were measured for
      each protocol. Players provided dRPE (CR100) for breathlessness (RPE-B) and leg
      muscle exertion (RPE-L) immediately on exercise termination (RPE-B0, RPE-L0) and
      30 min postexercise (RPE-B30, RPE-L30). Data were analyzed using magnitude-based
      inferences. RESULTS: There were clear between-protocols differences for VO2max
      (cycle 46.5 +/- 6.3 vs treadmill 51.0 +/- 5.1 mL . kg-1 . min-1, mean difference 
      9.2%; +/-90% confidence limits 3.7%), HRmax (184.7 +/- 12.7 vs 196.7 +/- 7.8
      beats/min, -6.0%; +/-1.7%), B[La]peak (9.7 +/- 2.1 vs 8.5 +/- 2.0 mmol/L, 15%; +/
      10%), and DeltaCMJH (-7.1 +/- 4.2 vs 0.6 +/- 3.6 cm, -23.2%; +/- 5.4%). Clear
      between-protocols differences were recorded for RPE-B0 (78.0 +/- 11.7 vs 94.7 +/-
      9.5 AU, -18.1%; +/- 4.5%), RPE-L0 (92.6 +/- 9.7 vs 81.3 +/- 14.1 AU, 15.3%; +/-
      7.6%), RPE-B30 (70 +/- 11 vs 82 +/- 13 AU, -13.8%; +/- 7.3%), and RPE-L30 (86 +/-
      12 vs 65 +/- 19 AU, 37%; +/-17%). A substantial timing effect was observed for
      dRPE, with moderate to large reductions in all scores 30 min postexercise
      compared with scores collected on exercise termination. CONCLUSION: dRPE enhance
      the precision of internal-load measurement and therefore represent a worthwhile
      addition to training-load-monitoring procedures.

PMID- 26218100
TI  - Recruitment Dynamics of the Relict Palm, Jubaea chilensis: Intricate and
      Pervasive Effects of Invasive Herbivores and Nurse Shrubs in Central Chile.
AB  - Shrubs can have a net positive effect on the recruitment of other species,
      especially relict species in dry-stressful conditions. We tested the effects of
      nurse shrubs and herbivory defoliation on performance (survival and growth) of
      nursery-grown seedlings of the largest living palm, the relict wine palm Jubaea
      chilensis. During an 18-month period, a total of more than 300 seedlings were
      exposed to of four possible scenarios produced by independently weakening the
      effects of nurse shrubs and browsers. The experiment followed a two-way fully
      factorial design. We found consistent differences in survival between protected
      and unprotected seedlings (27.5% and 0.7%, respectively), and herbivory had a
      dramatic and overwhelmingly negative effect on seedling survival. The invasive
      rabbit (Oryctolagus cuniculus) is clearly creating a critical bottleneck in the
      regeneration process and might, therefore, partially explain the general lack of
      natural regeneration of wine palms under natural conditions. Apparently biotic
      filters mediated by ecological interactions are more relevant in the early stages
      of recruitment than abiotic, at least in invaded sites of central Chile. Our data
      reveal that plant-plant facilitation relationship may be modulated by plant
      animal interactions, specifically by herbivory, a common and widespread
      ecological interaction in arid and semi-arid environments whose role has been
      frequently neglected. Treatments that protect young wine palm seedlings are
      mandatory to enable the seedlings to attain a height at which shoots are no
      longer vulnerable to browsing. Such protection is an essential first step toward
      the conservation and reintroduction of this emblematic and threatened species. 

PMID- 26218101
TI  - Rotational Diffusion of Charged and Nondipolar Solutes in Ionic Liquid-Organic
      Solvent Mixtures: Evidence for Stronger Specific Solute-Solvent Interactions in
      Presence of Organic Solvent.
AB  - Rotational diffusion of a charged solute, rhodamine 110 (R110), and a nondipolar
      solute, 2,5-dimethyl-1,4-dioxo-3,6-diphenylpyrrolo[3,4-c]pyrrole (DMDPP), has
      been investigated in ionic liquids, 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([BMIM][Tf2N]) and 1-butyl-3-methylimidazolium
      tris(pentafluoroethyl)trifluorophosphate ([BMIM][FAP]), with 0.8 mole fraction of
      dibenzyl ether (DBE). This study has been undertaken to find out how specific
      interactions between the solute and the ionic liquid are affected upon dilution
      with a nondipolar solvent. It has been observed that at a given viscosity (eta)
      and temperature (T), the reorientation times of R110 increase by 40-60% in the
      ionic liquid-organic solvent mixtures compared to ones in the corresponding neat
      ionic liquids. In the case of DMDPP, the influence of DBE is less pronounced, and
      its reorientation times increase by 25-50% at a given eta/T. The addition of DBE
      weakens the numerous interactions prevailing between the cations and the anions
      of the ionic liquids, which results in stronger specific interactions between the
      solutes and the constituent ions, consequently leading to slower rotation of the
      solutes. 

PMID- 26218102
TI  - Objects Mediate Goal Integration in Ventrolateral Prefrontal Cortex during Action
      Observation.
AB  - Actions performed by others are mostly not observed in isolation, but embedded in
      sequences of actions tied together by an overarching goal. Therefore, preceding
      actions can modulate the observer's expectations in relation to the currently
      perceived action. Ventrolateral prefrontal cortex (vlPFC), and inferior frontal
      gyrus (IFG) in particular, is suggested to subserve the integration of episodic
      as well as semantic information and memory, including action scripts. The present
      fMRI study investigated if activation in IFG varies with the effort to integrate
      expected and observed action, even when not required by the task. During an fMRI
      session, participants were instructed to attend to short videos of single actions
      and to deliver a judgment about the actor's current goal. We manipulated the
      strength of goal expectation induced by the preceding action, implementing the
      parameter "goal-relatedness" between the preceding and the currently observed
      action. Moreover, since objects point to the probability of certain actions, we
      also manipulated whether the current and the preceding action shared at least one
      object or not. We found an interaction between the two factors goal-relatedness
      and shared object: IFG activation increased the weaker the goal-relatedness
      between the preceding and the current action was, but only when they shared at
      least one object. Here, integration of successive action steps was triggered by
      the re-appearing (shared) object but hampered by a weak goal-relatedness between
      the actually observed manipulation. These findings foster the recently emerging
      view that IFG is enhanced by goal-related conflicts during action observation. 

PMID- 26218104
TI  - Reflections from a chair: Leadership of a clinical department at an academic
      medical center.
AB  - The leadership position of an academic departmental chair can be a positive and
      rewarding opportunity. These rewards principally stem from the success of the
      faculty, residents, other trainees, nurses, and everyone supporting the
      department. With health care reform and the constraints of the federal budget,
      increasing attention and time has become directed toward administrative
      management. There are multiple and often competing constituencies and agendas
      requiring thoughtful strategies to achieve departmental goals. The objectives of
      a chair are advancing patient care, education, and research. True excellence of a
      department is achieved by the innovation of its faculty.

PMID- 26218105
TI  - Global Efforts to Generate Evidence for Vision 2020.

PMID- 26218106
TI  - Prevalence and Causes of Visual Impairment and Blindness in Shanxi Province,
      China.
AB  - PURPOSE: To estimate the prevalence and causes of visual impairment and blindness
      in Shanxi Province, China. METHODS: Data were obtained from the Second National
      Sampling Survey of Disability conducted in 2006. Blindness and visual impairment
      were defined as best corrected visual acuity <3/60 and <6/18, respectively, in
      the better-seeing eye. Standardized ophthalmologic examinations were administered
      to participants aged 0-80 years in 2006. Visual acuity (VA) was measured using a
      Standard Logarithmic Visual Acuity E chart (Snellen) for subjects aged 7 years
      and older. Participants younger than 7 years were examined using special
      experiments or the Childhood Graphical Visual Chart. RESULTS: The prevalence of
      visual impairment and blindness in Shanxi was estimated to be 0.6% (466/75,016)
      among persons up to 80 years old. The prevalence in rural areas (0.7%;
      351/48,137) was significantly higher than that in urban areas (0.4%; 115/26,879)
      and was higher in females (0.8%; 298/36,933) than in males (0.4%; 168/38,083).
      The most common cause of visual impairment and blindness was cataract (44.9%),
      followed by retinopathy and choroidopathy (12.5%), hereditary and developmental
      disorders (10.3%), corneal disease (5.2%), and refractive error (4.9%).
      CONCLUSION: Prevalences of visual impairment and blindness in women and in rural
      areas were higher than in men and urban areas, and increased with age. Cataract
      was the most prevalent cause of visual impairment and blindness. Based on the
      findings from this study, we suggest that provision of support and welfare
      services should be organized.

PMID- 26218107
TI  - Prevalence of Visual Impairment and Refractive Errors in Children of South Sinai,
      Egypt.
AB  - PURPOSE: To assess the prevalence and causes of visual impairment in children of
      South Sinai, and to evaluate outcomes of rehabilitation programs. METHODS:
      Population-based, cross-sectional analysis of 2070 healthy school children
      screened for visual impairment from 2009 through 2010 in cities of South Sinai
      and their surrounding Bedouin settlements. Visual acuity (VA) was tested using
      Snellen charts followed by cycloplegic autorefractometry for cases with
      presenting VA <= 6/9. Appropriate eyeglasses were prescribed and VA re-evaluated.
      RESULTS: This study included 1047 boys and 1023 girls, mean age 10.7 +/- 3.1
      years. Visual impairment (uncorrected VA <= 6/9) was detected in 29.4% of
      children, while 2.0% had moderate-severe visual impairment (uncorrected VA <=
      6/24). There were statistically significant differences in prevalence of visual
      impairment between the studied cities (p < 0.05), with the highest prevalence in
      Abu Redis. Prevalence of visual impairment was significantly higher among girls
      (p < 0.05) and those with positive consanguinity (p < 0.05). Bedouin children
      showed significantly lower prevalences of visual impairment. Only age was a
      reliable predictor of visual impairment (odds ratio 0.94, p < 0.0001). Ophthalmic
      examination revealed other disorders, e.g. dry eye (4.74%), squint (2.37%),
      exophthalmos (1.58%) and ptosis (0.79%). VA significantly improved in children
      who received spectacles (p < 0.001). CONCLUSION: A total of 29.4% of South Sinai
      children had some form of visual impairment, 90.32% of which comprised refractive
      errors (mainly astigmatism) which were significantly corrected with eyeglasses.
      VA screening and correction of refractive errors are of the utmost importance for
      ensuring better visual outcomes and improved school performance.

PMID- 26218108
TI  - Intermediate-Term Cataract Surgery Outcomes from Rural Provinces in Lao People's
      Democratic Republic.
AB  - PURPOSE: Limited data are available about cataract surgery outcomes from
      developing regions in South-East Asia, but are necessary to monitor the impact of
      ongoing program delivery as outlined in the World Health Organization Vision 2020
      directives. METHODS: We conducted a retrospective cohort study of 488 eyes of 449
      patients who had undergone cataract surgery in 2011 in Luang Prabang and
      Xayaboury provinces of northwestern Lao People's Democratic Republic (Lao PDR).
      The study included 400 eyes of 361 subjects (80.4% of the target population). The
      main outcomes were presenting and pinhole visual acuity (VA). RESULTS: Subjects'
      mean age was 68 years (standard deviation 12.1 years); 52.6% were women.
      Preoperative presenting VA in the operated eye was <6/60 in all patients where
      presenting VA data was available (76.4%). Presenting VA in the operated eye was
      >6/18 in 185/400 eyes (46.3%, 95% confidence interval, CI, 41.4-51.2%), <6/18
      6/60 in 177/400 (44.3%, 95% CI 39.4-49.2%) and <6/60 in 38/400 (9.5%, 95% CI 6.6
      12.4%). VA improved two or more lines in 61/400 eyes (15.3%, 95% CI 11.7-18.8%)
      with pinhole. Relative afferent pupillary defect was present in 13/400 eyes
      (3.3%, 95% CI 1.5-5.0%). CONCLUSION: Presenting postoperative VA did not meet the
      World Health Organization criteria for good outcomes. Further study is required
      to determine specific factors contributing to adverse outcomes in this
      population.

PMID- 26218109
TI  - Evaluation of Cataract Surgery Outcomes at the Ban Phaeo Mobile Eye Clinic,
      Thailand.
AB  - PURPOSE: To evaluate the quality and efficacy of the Ban Phaeo Mobile Eye Clinic
      (BPMEC) model in providing cataract surgery to rural Thailand. METHODS:
      Retrospective review of 4-week postoperative visual acuity (VA) of 7040 patients
      receiving unilateral cataract surgery at 75 sites from October 2008 to March
      2011. BPMEC conducted screening, surgery, and follow-up at partnering local
      hospitals that otherwise do not offer eye care. The primary outcome was
      achievement of VA >=20/70, which was secondarily analyzed by cataract extraction
      method (phacoemulsification, phaco, or extracapsular cataract extraction, ECCE)
      and intraocular lens (IOL) type (foldable acrylic or rigid
      polymethylmethacrylate). RESULTS: Preoperatively, 249 eyes (4%) had uncorrected
      VA >=20/70. Four weeks postoperatively, 5957 (85%) had VA >=20/70, 3288 (47%) had
      VA >=20/40, and 69 (1%) were lost to follow-up. Phaco was performed in 6324 eyes
      (90%), 1581 (25%) receiving foldable IOLs. A total of 1403 eyes (89%) undergoing
      phaco with a foldable IOL had postoperative VA >=20/70, compared to 4058 (85%)
      and 496 (69%) of those undergoing phaco with a rigid IOL (p < 0.05) and ECCE with
      a rigid IOL (p < 0.001), respectively. Overall, 37 eyes were left aphakic.
      Reported intraocular complications included zonular dehiscence (37 eyes),
      retained lens fragment (2 eyes), wound leakage (1 eye), and posterior capsule
      tear (1 eye). CONCLUSIONS: The 4-week uncorrected postoperative VAs met the World
      Health Organization's quality target of VA >=20/70 for eyes undergoing phaco and
      were comparable to those published by an urban hospital in Bangkok.

PMID- 26218110
TI  - Visual Acuity, Quality of Life and Visual Function Outcomes after Cataract
      Surgery in Bali.
AB  - PURPOSE: To assess post-cataract surgery intermediate-term (>6 months) data of
      visual acuity (VA), surgical complications, refractive outcomes, quality of life
      (QOL) and visual function (VF) from a non-governmental organization program in
      Indonesia. METHODS: Retrospective cohort study design. Participants were a
      selection of patients who underwent cataract surgery by the John Fawcett
      Foundation between 2006 and 2011, with at least 6 months follow-up. Patients
      underwent comprehensive ophthalmic examinations. QOL and VF questionnaires were
      administered. RESULTS: From a total of 1557 invited to attend, 547 patients
      participated; 99.8% of eyes had presenting VA <6/60. At day 1 postoperatively,
      52.1% of patients had a good outcome by World Health Organization criteria
      (unaided VA >= 6/18). Six months or later postoperatively, 85% of eyes had best
      corrected VA >= 6/18 and 5.6% of eyes had best-corrected VA < 3/60. At final
      follow-up, mean postoperative spherical equivalent refraction was -2.35 diopters
      (standard deviation 1.75, n = 542). On a scale of 1-100, median converted values
      for QOL were 25.0 preoperatively and 74.0 postoperatively, a statistically
      significant improvement (p < 0.001). Of eyes with VA better than 3/60 on
      postoperative day 1, 5.7% (95% confidence interval 3.6-7.9%) became blind (VA <
      3/60) at the 6-month or later time point. CONCLUSION: Cataract surgery in this
      population markedly improved QOL, despite a trend towards myopic refractive
      outcomes. These findings raise questions about biometric methodology, intraocular
      lens power calculations and refractive targets. Postoperative day 1 VA data may
      be a reasonable proxy of the intermediate-term rate of non-blind eyes.

PMID- 26218112
TI  - Special Issues on Trachoma.

PMID- 26218111
TI  - The Impact of Multimedia Education on Uptake of Comprehensive Eye Examinations in
      Rural China: A Randomized, Controlled Trial.
AB  - PURPOSE: To study the effect of multimedia education on acceptance of
      comprehensive eye examinations (CEEs), critical for detecting glaucoma and
      diabetic eye disease, among rural Chinese patients using a randomized, controlled
      design. METHODS: Patients aged >=40 years were recruited from 52 routine clinic
      sessions (26 intervention, 26 control) conducted at seven rural hospitals in
      Guangdong, China. Subjects answered demographic questionnaires, were tested on
      knowledge about CEEs and chronic eye disease, and were told the cost of
      examination (range US$0-8). At intervention sessions, subjects were cluster
      randomized to view a 10-minute video on the value of CEEs and retested. Control
      subjects were not retested. Trial outcomes were acceptance of CEEs (primary
      outcome) and final knowledge scores (secondary outcome). RESULTS: At baseline,
      >70% (p = 0.70) of both intervention (n = 241, 61.2 +/- 12.3 years) and control
      (n = 218, 58.4 +/- 11.7 years) subjects answered no knowledge questions
      correctly, but mean scores on the test (maximum 5 points) increased by 1.39
      (standard deviation 0.12) points (p < 0.001) after viewing the video.
      Intervention (73.0%) and control (72.9%) subjects did not differ in acceptance of
      CEEs (p > 0.50). In mixed-effect logistic regression models, acceptance of CEEs
      was associated with availability of free CEEs (odds ratio 18.3, 95% confidence
      interval 1.32-253.0), but not group assignment or knowledge score. Acceptance was
      97.5% (79/81) when free exams were offered. CONCLUSIONS: Education increased
      knowledge about but not acceptance of CEEs, which was generally high. Making CEEs
      free could further increase acceptance.

PMID- 26218113
TI  - Protein-polymer therapeutics: a macromolecular perspective.
AB  - The development of protein-polymer hybrids emerged several decades ago with the
      vision that their synergistic combination will offer macromolecular hybrids with
      manifold features to succeed as the next generation therapeutics. From the first
      generation of protein-polymer therapeutics represented by PEGylated proteins, the
      field has since advanced, reinforced by the progress in contemporary chemical
      techniques for designing polymeric scaffolds and protein engineering. Novel
      polymerization techniques that offer multifunctional strategies as well as a
      greater understanding of proteins and their biological behavior have both proven
      to be exceptional tools in the construction of these hybrid materials. In this
      review, we seek to summarize and highlight the recent progress in these semi
      synthetic protein hybrids in terms of their preparation, design, resulting
      bioarchitectures and bioactivities for their intended bio-applications. 

PMID- 26218114
TI  - Bone tissue regeneration: the role of scaffold geometry.
AB  - The geometry of porous scaffolds that are used for bone tissue engineering and/or
      bone substitution has recently been shown to significantly influence the cellular
      response and the rate of bone tissue regeneration. Most importantly, it has been
      shown that the rate of tissue generation increases with curvature and is much
      larger on concave surfaces as compared to convex and planar surfaces. In this
      work, recent discoveries concerning the effects of geometrical features of porous
      scaffolds such as surface curvature, pore shape, and pore size on the cellular
      response and bone tissue regeneration process are reviewed. In addition to
      reviewing the recent experimental observations, we discuss the mechanisms through
      which geometry affects the bone tissue regeneration process. Of particular
      interest are the theoretical models that have been developed to explain the role
      of geometry in the bone tissue regeneration process. We then follow with a
      section on the implications of the observed phenomena for geometrical design of
      porous scaffolds including the application of predictive computational models in
      geometrical design of porous scaffolds. Moreover, some geometrical concepts in
      the design of porous scaffolds such as minimal surfaces and porous structures
      with geometrical gradients that have not been explored before are suggested for
      future studies. We especially focus on the porous scaffolds manufactured using
      additive manufacturing techniques where the geometry of the porous scaffolds
      could be precisely controlled. The paper concludes with a general discussion of
      the current state-of-the-art and recommendations for future research. 

PMID- 26218115
TI  - MMP-9 triggered micelle-to-fibre transitions for slow release of doxorubicin.
AB  - Phenylacetyl-peptide amphiphiles were designed, which upon cleavage by a disease
      associated enzyme reconfigure from micellar aggregates to fibres. Upon this
      morphological change, a doxorubicin payload could be retained in the fibres
      formed, which makes them valuable carriers for localised formation of nanofibre
      depots for slow release of hydrophobic anticancer drugs. 

PMID- 26218116
TI  - Effective CpG DNA delivery using amphiphilic cycloamylose nanogels.
AB  - Unmethylated CpG oligodeoxynucleotides induce inflammatory immune responses
      through cytokine production and have attracted increasing attention as an
      immunostimulator. However, there remains a challenging issue of the use of
      'native CpG DNA'. In the present study, we prepared cationic nanometer-sized gels
      (nanogels) consisting of cycloamylose modified with cholesterol and
      diethylaminoethane to form hydrophobic cross-linking points and to add positively
      charged groups, respectively. The cationic nanogels and native CpG DNA formed
      nanometer-sized complexes. Complexes of native CpG DNA with cationic nanogels
      delivered native CpG DNA to macrophage-like cells and induced cytokine
      production. In addition, complexes of negative control oligonucleotides with
      cationic nanogels did not induce cytokine production, and the induction of
      cytokines using complexes of phosphorothioate-modified CpG with cationic nanogels
      was lower than that of native CpG DNA. These results suggest that the complex of
      native CpG DNA with cationic nanogels is a promising strategy for nucleic acid
      adjuvants. 

PMID- 26218117
TI  - Significance of surface charge and shell material of superparamagnetic iron oxide
      nanoparticle (SPION) based core/shell nanoparticles on the composition of the
      protein corona.
AB  - As nanoparticles (NPs) are increasingly used in many applications their safety
      and efficient applications in nanomedicine have become concerns. Protein coronas
      on nanomaterials' surfaces can influence how the cell "recognizes" nanoparticles,
      as well as the in vitro and in vivo NPs' behaviors. The SuperParamagnetic Iron
      Oxide Nanoparticle (SPION) is one of the most prominent agents because of its
      superparamagnetic properties, which is useful for separation applications. To
      mimic surface properties of different types of NPs, a core-shell SPION library
      was prepared by coating with different surfaces: polyvinyl alcohol polymer (PVA)
      (positive, neutral and negative), SiO2 (positive and negative), titanium dioxide
      and metal gold. The SPIONs with different surfaces were incubated at a fixed
      serum : nanoparticle surface ratio, magnetically trapped and washed. The tightly
      bound proteins were quantified and identified. The surface charge has a great
      impact on protein adsorption, especially on PVA and silica where proteins
      preferred binding to the neutral and positively charged surfaces. The importance
      of surface material on protein adsorption was also revealed by preferential
      binding on TiO2 and gold coated SPION, even negatively charged. There is no
      correlation between the protein net charge and the nanoparticle surface charge on
      protein binding, nor direct correlation between the serum proteins' concentration
      and the proteins detected in the coronas. 

PMID- 26218118
TI  - Purine-crosslinked injectable chitosan sponges promote oligodendrocyte progenitor
      cells' attachment and differentiation.
AB  - Oligodendrocyte Progenitor Cells (OPCs) reside in the central nervous system
      (CNS) and are responsible for remyelinating axons after a spinal cord injury
      (SCI). However, the remyelination process is incomplete and abnormal due to the
      inability of OPCs to fully differentiate at the site of injury. In this study a
      newly developed injectable chitosan sponge crosslinked using guanosine 5'
      diphosphate (GDP) was used to enhance OPC survival, attachment and
      differentiation. This purine-based biomaterial is the first of its kind and its
      inception was based on the growing body of literature concerning the role of
      purinergic signalling in the CNS. GDP-crosslinked chitosan sponges are rapidly
      gelling and can be easily administered in situ using an injection system based on
      a double-lumen design. The chitosan sponges prompted OPC differentiation even in
      the presence of mitogens. Moreover, neurotrophin-3 (NT-3) was successfully
      entrapped in the sponges and a sustained release for up to 30 days was achieved.
      OPCs were shown to differentiate into mature oligodendrocytes that express myelin
      basic protein (MBP) when cultured on sponges containing NT-3. These findings,
      along with the suitable physicochemical and biological properties, make these
      sponges conducive to use as viable therapeutic agents for enhancing remyelination
      post-SCI. 

PMID- 26218119
TI  - Immobilising proteins on silica with site-specifically attached modified silaffin
      peptides.
AB  - Immobilisation of proteins on solid supports such as silica is commonly applied
      to improve performance of enzymes under detrimental conditions and to allow
      enzyme recycling. Silica biomineralisation processes occurring in nature have
      recently inspired approaches towards mild, biomimetic silica formation. In
      diatoms, complex posttranslationally modified silaffin peptides are directly
      involved in formation and patterning of silica cell walls. Here, chemically
      modified silaffin peptides are used to establish a novel strategy for silica
      immobilisation of target proteins. Silaffin variants carrying different
      modifications are covalently linked to eGFP and thioredoxin using expressed
      protein ligation. Covalent eGFP- and thioredoxin-silaffin conjugates are able to
      efficiently precipitate silica and control silica properties by choice of
      different silaffin modifications leading to functional encapsulation of these
      proteins in silica particles. Covalent protein-silaffin conjugates lead to a
      distinctly more efficient and homogenous encapsulation of proteins in silica,
      superior to random protein entrapment resulting from simple co-precipitation.
      Silica-immobilised proteins are confirmed to be fully active and stabilised
      against denaturation. 

PMID- 26218120
TI  - Dissolution and degradation of Fmoc-diphenylalanine self-assembled gels results
      in necrosis at high concentrations in vitro.
AB  - Herein we report an approach to assess in vitro cellular responses to the
      dissolution or degradation products from Fmoc-diphenylalanine (Fmoc-FF) self
      assembled hydrogels. Three cell lines were used in these studies and two-way
      ANOVA was used to assess (i) the age of gel dissolution and degradation products
      and (ii) exposure time on cell fate and state, using viability assays in
      conjunction with time-lapse fluorescence and high-resolution scanning electron
      microscopy investigation. The studies show that leaching time but not the
      exposure time affects the overall cell viability. The cytotoxic effect was only
      observed once the gel is completely dissolved. Further analysis revealed that the
      principal mechanism of cell death is necrosis. In addition, the effect of
      chemotherapeutics (5-fluorouracil and paclitaxel) released from the Fmoc-FF gel
      (with addition before and after gelation) on colorectal cancer cells were
      investigated using this methodology, demonstrating enhanced activity of these
      drugs compared to bulk control. This enhanced activity, however, appears to be a
      combination of the apoptosis caused by the cancer drugs and necrosis caused by
      gel dissolution and degradation products. Given that in vivo studies by others on
      Fmoc-peptides that this material is not harmful to animals, our work highlights
      that conventional in vitro cellular assays may yield conflicting messages when
      used for the evaluation of cytotoxicity and drug release from self-assembled gels
      such as Fmoc-FF and that better in vitro models, (e.g. 3D cell culture systems)
      need to be developed to evaluate these materials for biomedical applications. 

PMID- 26218121
TI  - Enhancement of deoxyribozyme activity by cationic copolymers.
AB  - Deoxyribozymes, or DNAzymes, are DNA molecules with enzymatic activity. DNAzymes
      with ribonuclease activity have various potential applications in biomedical and
      bioanalytical fields; however, most constructs have limited turnover despite
      optimization of reaction conditions and DNAzyme structures. A cationic comb-type
      copolymer accelerates DNA hybridization and strand exchange rates, and we
      hypothesized that the copolymer would enhance deoxyribozyme activity by promoting
      turnover. The copolymer did not change DNAzyme activity under single-turnover
      conditions, suggesting that the copolymer affects neither the folding structure
      of DNAzyme nor the association of a divalent cation, a catalytic cofactor, to
      DNAzyme. The copolymer enhanced activity of the evaluated DNAzyme over a wide
      temperature range under multiple-turnover conditions. The copolymer increased the
      DNAzyme kcat/KM by fifty-fold at 50  degrees C, the optimal temperature for the
      DNAzyme in the absence of the copolymer. The acceleration effect was most
      significant when the reaction temperature was slightly higher than the melting
      temperature of the enzyme/substrate complex; acceleration of two orders of
      magnitude was observed. We concluded that the copolymer accelerated the turnover
      step without influencing the chemical cleavage step. In contrast to the
      copolymer, a cationic surfactant, CTAB, strongly inhibited the DNAzyme activity
      under either single- or multiple-turnover conditions. 

PMID- 26218122
TI  - The transfection efficiency of calix[4]arene-based lipids: the role of the alkyl
      chain length.
AB  - The size, surface charge, and microstructure of lipoplexes comprising cationic
      lipids and nucleic acids are important factors for transfection efficiency. As
      these properties are largely determined by the cationic lipids used, a number of
      studies on the relationship between cationic lipids and the transfection
      efficiency have been reported. Among the many cationic lipids, lipids with
      multivalent cationic head groups are expected to be potent transfection reagents.
      Here, we prepared calix[4]arene-based lipids with different alkyl chain lengths
      from C3 to C15 and evaluated the relationship between the alkyl chain length and
      the transfection efficiency. C6 lipoplexes exhibited the highest transfection
      efficiency among all lipoplexes. The gene expression with C9 and C12 lipoplexes
      was slightly lower than that with C6 lipoplexes. C3 lipoplexes hardly induced
      gene expression, while C15 lipoplexes exhibited no complexation with plasmid DNA.
      Although all lipoplexes exhibited nearly identical characteristics, they
      exhibited different behaviours in terms of the interactions between the
      lipoplexes and anionic micelles comprising phosphatidylserine, a model of
      endosomal vehicle. After mixing with phosphatidylserine micelles, C6 lipoplexes
      released the bound plasmid DNA at pH 5 but not at pH 7, indicating that they can
      interact with the late endosomal membrane after being incorporated into cells. No
      plasmid DNA was released from C9 or C12 lipoplexes at either pH values. Thus, the
      alkyl chain length of cationic lipids is related to their interaction with the
      endosomal compartment and can provide a basis for the design of novel
      transfection reagents. 

PMID- 26218123
TI  - The endocytic pathway and therapeutic efficiency of doxorubicin conjugated
      cholesterol-derived polymers.
AB  - Previously synthesized poly(methacrylic acid-co-cholesteryl methacrylate) P(MAA
      co-CMA) copolymers were examined as potential drug delivery vehicles. P(MAA-co
      CMA) copolymers were fluorescently labelled and imaged in SHEP and HepG2 cells.
      To understand their cell internalization pathway endocytic inhibition studies
      were conducted. It was concluded that P(MAA-co-CMA) are taken up by the cells via
      clathrin-independent endocytosis (CIE) (both caveolae mediated and cholesterol
      dependent endocytosis) mechanisms. The formation and characterization of P(MAA-co
      CMA)-doxorubicin (DOX) nanocomplexes was investigated by fluorescence lifetime
      imaging microscopy (FLIM), UV-Visible spectroscopy (UV-Vis) and dynamic light
      scattering (DLS) studies. The toxicity screening between P(MAA-co-CMA)-DOX
      nanocomplexes (at varying w/w ratios) and free DOX, revealed nanocomplexes to
      exhibit higher cytotoxicity towards cancer cells in comparison to normal cells.
      FLIM and confocal microscopy were employed for investigating the time-dependent
      release of DOX in SHEP cells and the cellular uptake profile of P(MAA-co-CMA)-DOX
      nanocomplexes in cancer and normal cell lines, respectively. The endocytic
      pathway of P(MAA-co-CMA)-DOX nanocomplexes were examined in SHEP and HepG2 cells
      via flow cytometry revealing the complexes to be internalized through both
      clathrin-dependent (CDE) and CIE mechanisms. The drug delivery profile, reported
      herein, illuminates the specific endocytic route and therapeutic efficiency of
      P(MAA-co-CMA)-DOX nanocomplexes strongly suggesting these particles to be
      promising candidates for in vivo applications. 

PMID- 26218124
TI  - Media additives to promote spheroid circularity and compactness in hanging drop
      platform.
AB  - Three-dimensional spheroid cultures have become increasingly popular as drug
      screening platforms, especially with the advent of different high throughput
      spheroid forming technologies. However, comparing drug efficacy across different
      cell types in spheroid culture can be difficult due to variations in spheroid
      morphologies and transport characteristics. Improving the reproducibility of
      compact, circular spheroids contributes to standardizing and increasing the
      fidelity of the desired gradient profiles in these drug screening three
      dimensional tissue cultures. In this study we discuss the role that circularity
      and compaction has on spheroids, and demonstrate the impact methylcellulose
      (MethoCel) and collagen additives in the culture media can contribute to more
      compact and circular spheroid morphology. We demonstrate that improved spheroid
      formation is not a simple function of increased viscosity of the different
      macromolecule additives, suggesting that other macromolecular characteristics
      contribute to improved spheroid formation. Of the various macromolecular
      additives tested for hanging drop culture, MethoCel provided the most desirable
      spheroid formation. Additionally, the higher viscosity of MethoCel-containing
      media improved the ease of imaging of cellular spheroids within hanging drop
      cultures by reducing motion-induced image blur. 

PMID- 26218125
TI  - A novel function of BMHP1 and cBMHP1 peptides to induce the osteogenic
      differentiation of mesenchymal stem cells.
AB  - Bone marrow homing peptide 1 (BMHP1), which was derived from a phage display
      peptide library (PDPL), is known to be home to bone marrow and bind to stem
      cells. For the first time, the effect of BMHP1 on the differentiation behavior of
      mesenchymal stem cells (MSCs) was evaluated. BMHP1 was tethered to modified
      quartz substrates, and MSCs were seeded on the substrates. It was found that
      BMHP1 could enhance cell adhesion and proliferation. More importantly, we found
      that BMHP1 could induce osteogenic differentiation either with a maintenance
      medium (DMEM) or osteogenic differentiation medium (ODM). Cyclic BMHP1 (cBMHP1)
      was further synthesized and it was found that cBMHP1 also exhibit a similar, but
      slightly worse effect on the osteogenic differentiation of MSCs as compared to
      BMHP1. This work enlightens us on the fact that BMHP1 and cBMHP1 may be used as
      osteogenic stimulators for MSCs based therapy. 

PMID- 26218126
TI  - Surface modulation of complex stiffness via layer-by-layer assembly as a facile
      strategy for selective cell adhesion.
AB  - In-stent restenosis and thrombosis are the main severe problems that occur after
      the percutaneous vascular intervention. The competition between endothelial cells
      (ECs) and smooth muscle cells (SMCs) plays a key role during these pathological
      changes. The regulation of this competition offers new opportunities to design
      biomaterials in the cardiovascular fields. Bioactive molecules have been
      typically employed to increase EC adhesion and thereafter to enhance EC
      competitiveness; however, this method is associated with limitations from the
      point of view of practical and industrial applications. Herein, we present an
      approach to enhance EC competitiveness over that of SMC through the selective EC
      adhesion, which is achieved by modulating a complex surface stiffness based on
      the technique of layer-by-layer (LbL) assembly. This complex stiffness can be
      achieved by regulating the thickness of multilayer films coordinating with a
      rigid underlying substrate. The selective cell adhesion is attributed to changes
      in the complex surface stiffness and a different intrinsic property between ECs
      and SMCs. This study provides a facile and broadly applicable approach for the
      purpose of the enhancement of EC competitiveness over that of SMC, which has
      great potential for the development of cell-based functional biomaterials in the
      cardiovascular field. 

PMID- 26218127
TI  - Coupled delivery of imatinib mesylate and doxorubicin with nanoscaled polymeric
      vectors for a sustained downregulation of BCR-ABL in chronic myeloid leukemia.
AB  - In this work, we have investigated the potential benefits of combining
      biodegradable pH sensitive core-shell PCL NPs loaded with IM and enzyme sensitive
      polyelectrolyte complexes (PECs) loaded with doxorubicin (DOX). Our in vitro
      studies confirmed the excellent antileukemic activity of dual drug loaded
      nanoparticles on CML cells. As compared with a drug alone, co-treatment with IM
      and DOX loaded in nanoparticles allowed a sustained downregulation of BCR-ABL and
      significant CML stem cell death. This furthermore showed that couple formulation
      of nanoparticles enhanced the drugs' kinetics and efficacy, combined with the pH
      sensibility of core-shell PCL NPs loaded with IM and enzyme sensitive
      polyelectrolyte complexes (PECs) loaded with DOX. Our study demonstrates that
      dual drug loaded nanoparticles work in a synergistic manner, lowering the dose
      and confirming that both drugs reach the target cell specifically, maximizing the
      cytotoxicity while minimizing the chances of cell resistance to any one drug. 

PMID- 26218128
TI  - Evaluation of dense collagen matrices as medicated wound dressing for the
      treatment of cutaneous chronic wounds.
AB  - Cutaneous chronic wounds are characterized by an impaired wound healing which may
      lead to infection and amputation. When current treatments are not effective
      enough, the application of wound dressings is required. To date, no ideal
      biomaterial is available. In this study, highly dense collagen matrices have been
      evaluated as novel medicated wound dressings for the treatment of chronic wounds.
      For this purpose, the structure, mechanical properties, swelling ability and in
      vivo stability of matrices concentrated from 5 to 40 mg mL(-1) were tested. The
      matrix stiffness increased with the collagen concentration and was associated
      with the fibril density and thickness. Increased collagen concentration also
      enhanced the material resistance against accelerated digestion by collagenase.
      After subcutaneous implantation in rats, dense collagen matrices exhibited high
      stability without any degradation after 15 days. The absence of macrophages and
      neutrophils evidenced their biocompatibility. Subsequently, dense matrices at 40
      mg mL(-1) were evaluated as drug delivery system for ampicillin release. More
      concentrated matrices exhibited the best swelling abilities and could absorb 20
      times their dry weight in water, allowing for an efficient antibiotic loading
      from their dried form. They released efficient doses of antibiotics that
      inhibited the bacterial growth of Staphylococcus Aureus over 3 days. In parallel,
      they show no cytotoxicity towards human fibroblasts. These results show that
      dense collagen matrices are promising materials to develop medicated wound
      dressings for the treatment of chronic wounds. 

PMID- 26218129
TI  - The effects of poly(dimethylsiloxane) surface silanization on the mesenchymal
      stem cell fate.
AB  - In recent years, poly(dimethylsiloxane) (PDMS)-based microfluidic devices have
      become very popular for on-chip cell investigation. Maintenance of mammalian cell
      adhesion on the substrate surface is crucial in determining the cell viability,
      proliferation and differentiation. However, the inherent hydrophobicity of PDMS
      is unfavourable for cell culture, causing cells to eventually dislodge from the
      surface. Although physically adsorbed matrix proteins can promote initial cell
      adhesion, this effect is usually short-lived. To address this critical issue, in
      this study, we employed (3-aminopropyl) triethoxy silane (APTES) and cross-linker
      glutaraldehyde (GA) chemistry to immobilize collagen type 1 (Col1) on PDMS. These
      modified surfaces are highly efficient to support the adhesion of mesenchymal
      stem cells (MSCs) with no deterioration of their potency. Significant changes of
      the native PDMS surface properties were observed with the proposed surface
      functionalization, and MSC adhesion was improved on PDMS surfaces modified with
      APTES + GA + Protein. Therefore, this covalent surface modification could
      generate a more biocompatible platform for stabilized cell adhesion. Furthermore,
      this modification method facilitated long-term cell attachment, which is
      favourable for successful induction of osteogenesis and cell sheet formation with
      an increased expression of osteogenic biomarkers and comparable extracellular
      matrix (ECM) constituent biomarkers, respectively. The surface silanization can
      be applied to PDMS-based microfluidic systems for long-term study of cellular
      development. Similar strategies could also be applied to several other substrate
      materials by appropriate combinations of self-assembled monolayers (SAMs) and ECM
      proteins. 

PMID- 26218130
TI  - Enhanced proteotoxic stress: one of the contributors for hyperthermic
      potentiation of the proteasome inhibitor bortezomib using magnetic nanoparticles.
AB  - The induction of hyperthermia using nanoparticles, known as magnetic fluid
      hyperthermia (MFH) in combination with anti-cancer drugs is an attractive method
      because of the potential for enhanced anti-cancer effects. Recent studies have
      shown that cells treated with MFH are more sensitive to the proteasome inhibitor
      bortezomib (BZ) than cells treated by hot water hyperthermia (HWH) under the same
      temperature conditions. We hypothesized that enhanced proteotoxic stress, caused
      by a combination of microtubule damage and an increase in the amount of
      aggregated proteins, may be partially responsible for this observation. To test
      this hypothesis MCF-7 cells were exposed to hyperthermic treatment (MFH or HWH)
      at 43  degrees C or 45  degrees C for 30 minutes. Then, aggresome formation and
      microtubule disruption studies at 30 minutes or 2.5 hours of recovery time were
      performed to evaluate the progressive effects induced by the two treatments. Cell
      viability at short and long times was evaluated. Aggresome formation and
      microtubule disruption results suggested that one of the mechanisms by which MFH
      enhances BZ cytotoxicity is the formation and subsequent accumulation of
      aggregated proteins in the cytosol due to the interruption of their transport to
      the perinuclear area through microtubules. Our data show evidence that MFH
      induces a more toxic and unmitigated proteotoxic stress than HWH under similar
      temperature conditions. 

PMID- 26218131
TI  - Engineering personalized neural tissue by combining induced pluripotent stem
      cells with fibrin scaffolds.
AB  - Induced pluripotent stem cells (iPSCs) are generated from adult somatic cells
      through the induction of key transcription factors that restore the ability to
      become any cell type found in the body. These cells are of interest for tissue
      engineering due to their potential for developing patient-specific therapies. As
      the technology for generating iPSCs advances, it is important to concurrently
      investigate protocols for the efficient differentiation of these cells to desired
      downstream phenotypes in combination with biomaterial scaffolds as a way of
      engineering neural tissue. For such applications, the generation of neurons
      within three dimensional fibrin scaffolds has been well characterized as a cell
      delivery platform for murine embryonic stem cells (ESCs) but has not yet been
      applied to murine iPSCs. Given that iPSCs have been reported to differentiate
      less effectively than ESCs, a key objective of this investigation is to maximize
      the proportion of iPSC-derived neurons in fibrin through the choice of
      differentiation protocol. To this end, this study compares two EB-mediated
      protocols for generating neurons from murine iPSCs and ESCs: an 8 day 4-/4+
      protocol using soluble retinoic acid in the last 4 days and a 6 day 2-/4+
      protocol using soluble retinoic acid and the small molecule sonic hedgehog
      agonist purmorphamine in the last 4 days. EBs were then seeded in fibrin
      scaffolds for 14 days to allow further differentiation into neurons. EBs
      generated by the 2-/4+ protocol yielded a higher percentage of neurons compared
      to those from the 4-/4+ protocol for both iPSCs and ESCs. The results demonstrate
      the successful translation of the fibrin-based cell-delivery platform for use
      with murine iPSCs and furthermore that the proportion of neurons generated from
      murine iPSC-derived EBs seeded in fibrin can be maximized using the 2-/4+
      differentiation protocol. Together, these findings validate the further
      exploration of 3D fibrin-based scaffolds as a method of delivering neuronal cells
      derived from iPSCs - an important step toward the development of iPSC-based
      tissue engineering strategies for spinal cord injury repair. 

PMID- 26218134
TI  - Human Stressors Are Driving Coastal Benthic Long-Lived Sessile Fan Mussel Pinna
      nobilis Population Structure More than Environmental Stressors.
AB  - Coastal degradation and habitat disruption are severely compromising sessile
      marine species. The fan shell Pinna nobilis is an endemic, vulnerable species and
      the largest bivalve in the Mediterranean basin. In spite of species legal
      protection, fan shell populations are declining. Models analyzed the
      contributions of environmental (mean depth, wave height, maximum wave height,
      period of waves with high energy and mean direction of wave source) versus human
      derived stressors (anchoring, protection status, sewage effluents, fishing
      activity and diving) as explanatory variables depicting Pinna nobilis populations
      at a mesoscale level. Human stressors were explaining most of the variability in
      density spatial distribution of fan shell, significantly disturbing benthic
      communities. Habitat protection affected P. nobilis structure and physical
      aggression by anchoring reveals a high impact on densities. Environmental
      variables instead played a secondary role, indicating that global change
      processes are not so relevant in coastal benthic communities as human-derived
      impacts. 

PMID- 26218133
TI  - Curcumin-Mediated HDAC Inhibition Suppresses the DNA Damage Response and
      Contributes to Increased DNA Damage Sensitivity.
AB  - Chemo- and radiotherapy cause multiple forms of DNA damage and lead to the death
      of cancer cells. Inhibitors of the DNA damage response are candidate drugs for
      use in combination therapies to increase the efficacy of such treatments. In this
      study, we show that curcumin, a plant polyphenol, sensitizes budding yeast to DNA
      damage by counteracting the DNA damage response. Following DNA damage, the Mec1
      dependent DNA damage checkpoint is inactivated and Rad52 recombinase is degraded
      by curcumin, which results in deficiencies in double-stand break repair. Additive
      effects on damage-induced apoptosis and the inhibition of damage-induced
      autophagy by curcumin were observed. Moreover, rpd3 mutants were found to mimic
      the curcumin-induced suppression of the DNA damage response. In contrast, hat1
      mutants were resistant to DNA damage, and Rad52 degradation was impaired
      following curcumin treatment. These results indicate that the histone deacetylase
      inhibitor activity of curcumin is critical to DSB repair and DNA damage
      sensitivity. 

PMID- 26218136
TI  - Tocilizumab-induced pustular drug eruption.

PMID- 26218137
TI  - Actinotetraose L, a new tetrasaccharide derivative isolated from the mycelia of
      Amycolatopsis sp. HCa1.
AB  - A new tetrasaccharide derivative, actinotetraose L (1), was isolated from the
      methanol extract of the mycelia of the grasshopper-associated rare
      actinobacterium Amycolatopsis sp. HCa1. The structure of the new compound was
      elucidated by a combination of 1D, 2D NMR (HMQC, HMBC, COSY, and NOESY), and HR
      ESI-MS analyses as O-{3,4-di-O-[(E)-2-ethyl-2-butenoyl]- beta-D-glucopyranosyl-(1
      -> 2)}-O-{3,4-di-O-[(E)-2-methyl-2-butenoyl]-beta-D-glucopyranosyl-(1 -> 2)}-6,6
      di-O-[(E)-2-methyl-2-butenoyl]-alpha-D-glucopyranosyl-(1 -> 1)-alpha-D
      glucopyranoside. The immunosuppressive activity and cytotoxicity of the compound
      were evaluated by T-cell viability and MTT assays. Nonetheless, no significant
      activity was observed. 

PMID- 26218135
TI  - STIM and ORAI proteins in the nervous system.
AB  - Stromal interaction molecules (STIM) 1 and 2 are sensors of the calcium
      concentration in the endoplasmic reticulum. Depletion of endoplasmic reticulum
      calcium stores activates STIM proteins which, in turn, bind and open calcium
      channels in the plasma membrane formed by the proteins ORAI1, ORAI2, and ORAI3.
      The resulting store-operated calcium entry (SOCE), mostly controlled by the
      principal components STIM1 and ORAI1, has been particularly characterized in
      immune cells. In the nervous system, all STIM and ORAI homologs are expressed.
      This review summarizes current knowledge on distribution and function of STIM and
      ORAI proteins in central neurons and glial cells, i.e. astrocytes and microglia.
      STIM2 is required for SOCE in hippocampal synapses and cortical neurons, whereas
      STIM1 controls calcium store replenishment in cerebellar Purkinje neurons. In
      microglia, STIM1, STIM2, and ORAI1 regulate migration and phagocytosis. The
      isoforms ORAI2 and ORAI3 are candidates for SOCE channels in neurons and
      astrocytes, respectively. Due to the role of SOCE in neuronal and glial calcium
      homeostasis, dysfunction of STIM and ORAI proteins may have consequences for the
      development of neurodegenerative disorders, such as Alzheimer's disease. 

PMID- 26218138
TI  - Prevalence of Inflammatory Bowel Disease Among Patients with Autism Spectrum
      Disorders.
AB  - BACKGROUND: The objective of this study was to measure the prevalence of
      inflammatory bowel disease (IBD) among patients with autism spectrum disorders
      (ASD), which has not been well described previously. METHODS: The rates of IBD
      among patients with and without ASD were measured in 4 study populations with
      distinct modes of ascertainment: a health care benefits company, 2 pediatric
      tertiary care centers, and a national ASD repository. The rates of IBD
      (established through International Classification of Diseases, Ninth Revision,
      Clinical Modification [ICD-9-CM] codes) were compared with respective controls
      and combined using a Stouffer meta-analysis. Clinical charts were also reviewed
      for IBD among patients with ICD-9-CM codes for both IBD and ASD at one of the
      pediatric tertiary care centers. This expert-verified rate was compared with the
      rate in the repository study population (where IBD diagnoses were established by
      expert review) and in nationally reported rates for pediatric IBD. RESULTS: In
      all of case-control study populations, the rates of IBD-related ICD-9-CM codes
      for patients with ASD were significantly higher than that of their respective
      controls (Stouffer meta-analysis, P < 0.001). Expert-verified rates of IBD among
      patients with ASD were 7 of 2728 patients in one study population and 16 of 7201
      in a second study population. The age-adjusted prevalence of IBD among patients
      with ASD was higher than their respective controls and nationally reported rates
      of pediatric IBD. CONCLUSIONS: Across each population with different kinds of
      ascertainment, there was a consistent and statistically significant increased
      prevalance of IBD in patients with ASD than their respective controls and
      nationally reported rates for pediatric IBD.

PMID- 26218139
TI  - Are Worries and Concerns Information Side Effects?

PMID- 26218140
TI  - Eosinophils and IL-33 Perpetuate Chronic Inflammation and Fibrosis in a Pediatric
      Population with Stricturing Crohn's Ileitis.
AB  - BACKGROUND: Fibrostenosis and stricture are well-recognized endpoints in Crohn's
      disease (CD). We hypothesized that stricturing CD is characterized by
      eosinophilia and epithelial IL-33. We proposed that eosinophil exposure to IL-33
      would perpetuate inflammatory chronicity and subsequent fibrostenosis. METHODS:
      We performed a retrospective study of 74 children with inflammatory and
      stricturing ileal CD comparing clinicopathological features to
      immunohistochemical measures of eosinophilia and IL-33. To scrutinize eosinophil
      patterns, we developed a novel eosinophil peroxidase score encompassing number,
      distribution, and degranulation. Human eosinophils and intestinal fibroblasts
      were cultured with IL-33 and IL-13, and inflammatory and remodeling parameters
      were assessed. Antieosinophil therapy was also administered to the Crohn's-like
      ileitis model (SAMP1/SkuSlc). RESULTS: Our novel eosinophil peroxidase score was
      more sensitive than H&E staining, revealing significant differences in eosinophil
      patterns, comparing inflammatory and stricturing pediatric CD. A significant
      relationship between ileal eosinophilia and complicated
      clinical/histopathological phenotype including fibrosis was determined. IL-33
      induced significant eosinophil peroxidase secretion and IL-13 production.
      Exposure to eosinophils in the presence of IL-33, "primed" fibroblasts to
      increase proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6), eosinophil
      associated chemokines (CCL24 and CCL26), and IL-13Ralpha2 production. Production
      of fibrogenic molecules (collagen 1A2, fibronectin, and periostin) increased
      after exposure of "primed" fibroblasts to IL-13. Epithelial-IL-33 was increased
      in pediatric Crohn's ileitis and strongly associated with clinical and
      histopathological activity, ileal eosinophilia, and complicated fibrostenotic
      disease. SAMP1/SkuSlc eosinophil-targeted treatment resulted in significant
      improvements in inflammation and remodeling. CONCLUSIONS: Our study of specimens
      from pediatric patients with ileal CD linked eosinophil patterns and IL-33 to
      fibrosis and suggested that these may contribute to the perpetuation of
      inflammation and subsequent stricture in pediatric CD.

PMID- 26218142
TI  - Can You Teach a Teen New Tricks? Problem Solving Skills Training Improves Oral
      Medication Adherence in Pediatric Patients with Inflammatory Bowel Disease
      Participating in a Randomized Trial.
AB  - BACKGROUND: Medication nonadherence is associated with higher disease activity,
      greater health care utilization, and lower health-related quality of life in
      pediatric inflammatory bowel diseases (IBD). Problem solving skills training
      (PSST) is a useful tool to improve adherence in patients with chronic diseases
      but has not been fully investigated in IBD. This study assessed feasibility,
      acceptability, and preliminary efficacy of PSST in pediatric IBD. METHODS:
      Recruitment occurred during outpatient clinic appointments. After completion of
      baseline questionnaires, families were randomized to a treatment group or wait
      list comparison group. The treatment group received either 2 or 4 PSST sessions.
      Youth health-related quality of life was assessed at 3 time points, and
      electronic monitoring of oral medication adherence occurred for the study
      duration. RESULTS: Seventy-six youth (ages 11-18 years) on an oral IBD
      maintenance medication participated. High retention (86%) and treatment fidelity
      rates (95%) supported feasibility. High satisfaction ratings (mean values >=4.2
      on 1-5 scale) supported intervention acceptability. Modest increases in adherence
      occurred after 2 PSST sessions among those with imperfect baseline adherence (d =
      0.41, P < 0.10). Significant increases in adherence after 2 PSST sessions were
      documented for participants aged 16 to 18 years (d = 0.95, P < 0.05).
      Improvements in health-related quality of life occurred after 2 PSST sessions. No
      added benefit of 4 sessions on adherence was documented (d = 0.05, P > 0.05).
      CONCLUSIONS: Phone-delivered PSST was feasible and acceptable. Efficacy estimates
      were similar to those of lengthier interventions conducted in other chronic
      illness populations. Older adolescents benefited more from the intervention than
      their younger counterparts.

PMID- 26218141
TI  - The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon
      Cancer Prevention.
AB  - BACKGROUND: Intestinal microbiota influences the progression of colitis
      associated colorectal cancer. With diet being a key determinant of the gut
      microbial ecology, dietary interventions are an attractive avenue for the
      prevention of colitis-associated colorectal cancer. Curcumin is the most active
      constituent of the ground rhizome of the Curcuma longa plant, which has been
      demonstrated to have anti-inflammatory, antioxidative, and antiproliferative
      properties. METHODS: Il10 mice on 129/SvEv background were used as a model of
      colitis-associated colorectal cancer. Starting at 10 weeks of age, wild-type or
      Il10 mice received 6 weekly intraperitoneal injections of azoxymethane (AOM) or
      phosphate-buffered saline (PBS) and were started on either a control or a
      curcumin-supplemented diet. Stools were collected every 4 weeks for microbial
      community analysis. Mice were killed at 30 weeks of age. RESULTS: Curcumin
      supplemented diet increased survival, decreased colon weight/length ratio, and,
      at 0.5%, entirely eliminated tumor burden. Although colonic histology indicated
      improvement with curcumin, no effects of mucosal immune responses have been
      observed in PBS/Il10 mice and limited effects were seen in AOM/Il10 mice. In wild
      type and in Il10 mice, curcumin increased bacterial richness, prevented age
      related decrease in alpha diversity, increased the relative abundance of
      Lactobacillales, and decreased Coriobacterales order. Taxonomic profile of
      AOM/Il10 mice receiving curcumin was more similar to those of wild-type mice than
      those fed control diet. CONCLUSIONS: In AOM/Il10 model, curcumin reduced or
      eliminated colonic tumor burden with limited effects on mucosal immune responses.
      The beneficial effect of curcumin on tumorigenesis was associated with the
      maintenance of a more diverse colonic microbial ecology.

PMID- 26218143
TI  - Presence of Granulomas in Mesenteric Lymph Nodes Is Associated with Postoperative
      Recurrence in Crohn's Disease.
AB  - BACKGROUND: The association between the presence of granulomas in the mesenteric
      lymph node (MLN) and postoperative recurrent Crohn's disease (CD) is unknown. Our
      aim was to assess the predictive value of the presence of granulomas in MLN as
      well as in bowel wall for postoperative recurrence of CD. METHODS: Patients with
      CD who underwent the index ileocolonic resection between 2004 and 2012 were
      included. Surgical pathology reports were reviewed for the presence and location
      of granulomas. The status of MLN granulomas was confirmed by re-review of
      surgical pathology specimen from randomly sampled patients by an expert
      pathologist. Both univariable and multivariable analyses were performed to assess
      the risk factors associated with postoperative recurrent CD. RESULTS: A total of
      194 patients were included. Granulomas were detected in the MLN in 23 patients
      (11.9%), and in the intestinal wall in 57 (29.4%). On Kaplan-Meier curve, the
      presence of granulomas in MLN was found to be a risk factor for postoperative
      endoscopic recurrence (P = 0.015) as well as surgical recurrence (P = 0.035). In
      contrast, granulomas in the bowel wall, which was not found to be associated with
      neither endoscopic recurrence (P = 0.94) or surgical recurrence (P = 0.56). On
      Cox proportional hazards regression analysis, the presence of MLN granulomas was
      independently associated with an increased risk for both postoperative endoscopic
      recurrence (hazard ratio [HR] = 1.91; 95% confidence interval [CI], 1.06-3.45; P
      = 0.031) and surgical recurrence (HR = 3.43; 95% CI, 1.18-9.99; P = 0.023).
      CONCLUSIONS: The presence of granulomas in MLN but not in intestine per se was
      found to be an independent risk factor for recurrence in CD patients undergoing
      ileocolonic resection.

PMID- 26218144
TI  - Circulating Interleukin 6 and Albumin, and Infliximab Levels Are Good Predictors
      of Recovering Efficacy After Dose Escalation Infliximab Therapy in Patients with
      Loss of Response to Treatment for Crohn's Disease: A Prospective Clinical Trial.
AB  - BACKGROUND: We aimed to clarify the efficacy, safety, and factors associated with
      remission on dose escalation in patients with Crohn's disease showing loss of
      response (LOR) to infliximab treatment of 5 mg/kg at 8-week intervals in a
      clinical trial. METHODS: Thirty-nine patients with LOR to 5 mg/kg infliximab
      therapy started treatment with 10 mg/kg per 8 weeks. LOR was defined as both a
      Crohn's Disease Activity Index of >=175 at 8 weeks after infusion of 5 mg/kg
      infliximab and a Crohn's Disease Activity Index increase of >=50 from 4 to 8
      weeks after infusion. RESULTS: At week 8 after the first infusion of 10 mg/kg,
      median (95% confidence interval) reduction in Crohn's Disease Activity Index of
      33 patients evaluated was 95.0 (70.0-134.0), meeting the primary endpoint.
      Remission rate at week 40 was 41% (16 of 39), with correlation noted between
      remission achievement and serum infliximab level (P = 0.036). Univariate analysis
      revealed that "infliximab trough level >=1 ug/mL," "interleukin 6 level <=2.41
      pg/mL," and "albumin level >=3.8 g/dL" before dose escalation were significantly
      associated with remission at week 40 (P = 0.017, P = 0.011, and P = 0.019,
      respectively), and these variables were correlated with each other (all: P <
      0.001). The cutoff infliximab level for remission was 0.42 ug/mL in receiver
      operating characteristic curve analysis. No adverse events related to dose
      escalation were observed. CONCLUSIONS: Doubling the infliximab dose safely led to
      remission in patients with Crohn's disease with LOR to 5 mg/kg treatment.
      Remission was associated with pre-escalation levels of infliximab, interleukin 6,
      and albumin. Our findings suggest that dose escalation while maintaining a
      certain level of infliximab is important in achieving remission.

PMID- 26218145
TI  - Robust Association Between Inflammatory Bowel Disease and Generalized Anxiety
      Disorder: Findings from a Nationally Representative Canadian Study.
AB  - BACKGROUND: Although the link between inflammatory bowel diseases (IBD) and
      depression is well accepted, less is known about the relationship between IBD and
      anxiety disorders and factors associated with anxiety among those with IBD.
      METHODS: Data were derived from the nationally representative 2012 Canadian
      Community Health Survey-Mental Health. The survey response rate was 68.9%. Two
      sets of analyses were undertaken. First, a series of logistic regression analyses
      were used to estimate the odd ratios of generalized anxiety disorder among those
      with IBD compared with those without (n = 22,522). The fully adjusted model
      controlled for sociodemographics, depression, substance abuse/dependence, pain,
      and adverse childhood experiences. Second, among those with IBD (n = 269),
      significant correlates of generalized anxiety disorder were identified using
      logistic regression. The presence of generalized anxiety disorder was determined
      using the WHO-CIDI lifetime criteria, and IBD was assessed by a self-reported
      health professional diagnosis. RESULTS: Individuals with IBD had over twice the
      odds of anxiety compared with those without IBD, even when controlling for a
      range of potential explanatory factors (odds ratio = 2.18; 95% confidence
      interval, 1.50-3.16). Controlling for chronic pain and childhood adversities
      attenuate the relationship the most. Among those with IBD, a history of childhood
      sexual abuse, female gender, and chronic pain are the strongest correlates of
      anxiety. Those with Crohn's and ulcerative colitis were equally vulnerable to
      generalized anxiety disorder. CONCLUSIONS: Our findings show that IBD is robustly
      related to generalized anxiety disorder. Health care professionals should be
      aware of the increased prevalence of generalized anxiety disorder among their
      patients with IBD, particularly women, those in chronic pain, and those with a
      history of childhood sexual abuse.

PMID- 26218146
TI  - Targeted Deletion of Btg1 and Btg2 Results in Homeotic Transformation of the
      Axial Skeleton.
AB  - Btg1 and Btg2 encode highly homologous proteins that are broadly expressed in
      different cell lineages, and have been implicated in different types of cancer.
      Btg1 and Btg2 have been shown to modulate the function of different
      transcriptional regulators, including Hox and Smad transcription factors. In this
      study, we examined the in vivo role of the mouse Btg1 and Btg2 genes in
      specifying the regional identity of the axial skeleton. Therefore, we examined
      the phenotype of Btg1 and Btg2 single knockout mice, as well as novel generated
      Btg1-/-;Btg2-/- double knockout mice, which were viable, but displayed a non
      mendelian inheritance and smaller litter size. We observed both unique and
      overlapping phenotypes reminiscent of homeotic transformation along the anterior
      posterior axis in the single and combined Btg1 and Btg2 knockout animals. Both
      Btg1-/- and Btg2-/- mice displayed partial posterior transformation of the
      seventh cervical vertebra, which was more pronounced in Btg1-/-;Btg2-/- mice,
      demonstrating that Btg1 and Btg2 act in synergy. Loss of Btg2, but not Btg1, was
      sufficient for complete posterior transformation of the thirteenth thoracic
      vertebra to the first lumbar vertebra. Moreover, Btg2-/- animals displayed
      complete posterior transformation of the sixth lumbar vertebra to the first
      sacral vertebra, which was only partially present at a low frequency in Btg1-/-
      mice. The Btg1-/-;Btg2-/- animals showed an even stronger phenotype, with L5 to
      S1 transformation. Together, these data show that both Btg1 and Btg2 are required
      for normal vertebral patterning of the axial skeleton, but each gene contributes
      differently in specifying the identity along the anterior-posterior axis of the
      skeleton. 

PMID- 26218147
TI  - Morphological Characteristics, Anatomical Structure, and Gene Expression: Novel
      Insights into Cytokinin Accumulation during Carrot Growth and Development.
AB  - Cytokinins have been implicated in normal plant growth and development. These
      bioactive molecules are essential for cell production and expansion in higher
      plants. Carrot is an Apiaceae vegetable with great value and undergoes
      significant size changes over the process of plant growth. However, cytokinin
      accumulation and its potential roles in carrot growth have not been elucidated.
      To address this problem, carrot plants at five stages were collected, and
      morphological and anatomical characteristics and expression profiles of cytokinin
      related genes were determined. During carrot growth and development, cytokinin
      levels were the highest at the second stage in the roots, whereas relatively
      stable levels were observed in the petioles and leaves. DcCYP735A2 showed high
      expression at stage 2 in the roots, which may contribute largely to the higher
      cytokinin level at this stage. However, expression of most metabolic genes did
      not follow a pattern similar to that of cytokinin accumulation, indicating that
      cytokinin biosynthesis was regulated through a complex network. Genes involved in
      cytokinin signal perception and transduction were also integrated to normal plant
      growth and development. The results from the present work suggested that
      cytokinins may regulate plant growth in a stage-dependent manner. Our work would
      shed novel insights into cytokinin accumulation and its potential roles during
      carrot growth. Further studies regarding carrot cytokinins may be achieved by
      modification of the genes involved in cytokinin biosynthesis, inactivation, and
      perception. 

PMID- 26218148
TI  - State Policies Influence Medicare Telemedicine Utilization.
AB  - BACKGROUND: Medicare policy regarding telemedicine reimbursement has changed
      little since 2000. Many individual states, however, have added telemedicine
      reimbursement for either Medicaid and/or commercial payers over the same period.
      Because telemedicine programs must serve patients from all or most payers, it is
      likely that these state-level policy changes have significant impacts on
      telemedicine program viability and utilization of services from all payers, not
      just those services and payers affected directly by state policy. This report
      explores the impact of two significant state-level policy changes-one expanding
      Medicaid telemedicine coverage and the other introducing telemedicine parity for
      commercial payers-on Medicare utilization in the affected states. MATERIALS AND
      METHODS: Medicare claims data from 2011-2013 were examined for states in the
      Great Lakes region. All valid claims for live interactive telemedicine
      professional fees were extracted and linked to their states of origin. Allowed
      encounters and expenditures were calculated in total and on a per 1,000 members
      per year basis to standardize against changes in the Medicare population by state
      and year. RESULTS: Medicare telemedicine encounters and professional fee
      expenditures grew sharply following changes in state Medicaid and commercial
      payer policy in the examined states. Medicare utilization in Illinois grew by
      173% in 2012 (over 2011) following Medicaid coverage expansion, and Medicare
      utilization in Michigan grew by 118% in 2013 (over 2012) following adoption of
      telemedicine parity for commercial payers. By contrast, annual Medicare
      telemedicine utilization growth in surrounding states (in which there were no
      significant policy changes during these years) varied somewhat but showed no
      discernible pattern. CONCLUSIONS: Although Medicare telemedicine policy has
      changed little since its inception, changes in state policies with regard to
      telemedicine reimbursement appear to have significant impacts on the practical
      viability of telemedicine programs that bill Medicare for telemedicine services.

PMID- 26218150
TI  - Atropine 0.01% Eyedrops Significantly Reduce the Progression of Childhood Myopia.
AB  - PURPOSE: Atropine 0.01% eyedrops have been shown to slow childhood myopic
      progression in primarily Asian populations. We studied its effects on an
      ethnically diverse population over a broad range of myopia. METHODS: A
      retrospective case-control study was performed on 60 children (6-15 years) with
      initial myopic spherical equivalents from -0.25 to -8.00 diopters (D). The
      primary outcome was the rate of myopic progression per year. Secondary outcomes
      were the proportion of subjects with slow or rapid myopic progression, atropine
      related side effects, and rates of myopic progression for subgroups with low,
      moderate, or higher initial myopia. RESULTS: The average initial age (10.2 years)
      and refraction (-2.0 D) were identical between groups. After 1.1+/-0.3 years
      follow-up, atropine subjects had significantly lower rates of myopic progression
      (-0.1+/-0.6 D/year) than controls (-0.6+/-0.4 D/year) (P=0.001), including 24 of
      32 (75%) with slow progression <=-0.25 D/year versus only 5 of 28 (18%) controls.
      Three atropine and 4 control subjects had rapid progression >=-1.00 D/year. For
      subjects with low initial myopia (<=-1.00 D), 9 of 11 (82%) atropine subjects had
      plano or slightly hyperopic refractive changes after 1 year, while 8 of 8 (100%)
      controls were more myopic. Only 3 atropine subjects complained of intermittent
      blur or light sensitivity, not symptomatic enough to discontinue treatment.
      CONCLUSIONS: Atropine 0.01% significantly reduced the rate of myopic progression
      over 1 year with minimal side effects. It appears most effective in children with
      low initial myopia and may not control rapid myopic progression in some patients.
      Stronger concentrations of atropine may be required to slow rapid myopic
      progression.

PMID- 26218151
TI  - Embracing the Age of Aquarius.

PMID- 26218149
TI  - HLA Class I Depleted hESC as a Source of Hypoimmunogenic Cells for Tissue
      Engineering Applications.
AB  - BACKGROUND: Rapidly improving protocols for the derivation of autologous cells
      from stem cell sources is a welcome development. However, there are many
      circumstances when off-the-shelf universally immunocompatible cells may be
      needed. Embryonic stem cells (ESCs) provide a unique opportunity to modify the
      original source of differentiated cells to minimize their rejection by
      nonautologous hosts. HYPOTHESIS: Immune rejection of nonautologous human
      embryonic stem cell (hESC) derivatives can be reduced by downregulating human
      leukocyte antigen (HLA) class I molecules, without affecting the ability of these
      cells to differentiate into specific lineages. METHODS AND RESULTS: Beta-2
      microglobulin (B2M) expression was decreased by lentiviral transduction using
      human anti-HLA class I light-chain B2M short hairpin RNA. mRNA levels of B2M were
      decreased by 90% in a RUES2-modified hESC line, as determined by quantitative
      real time-polymerase chain reaction analysis. The transduced cells were selected
      under puromycin pressure and maintained in an undifferentiated state. The latter
      was confirmed by Oct4 and Nanog expression, and by the formation of
      characteristic round-shaped colonies. B2M downregulation led to diminished HLA-I
      expression on the cell surface, as determined by flow cytometry. When used as
      target cells in a mixed lymphocyte reaction assay, transduced hESCs and their
      differentiated derivatives did not stimulate allogeneic T-cell proliferation.
      Using a cardiac differentiation protocol, transduced hESCs formed a confluent
      layer of cardiac myocytes and maintained a low level of B2M expression.
      Transduced hESCs were also successfully differentiated into a hepatic lineage,
      validating their capacity to differentiate into multiple lineages. CONCLUSIONS:
      HLA-I depletion does not preclude hESC differentiation into cardiac or hepatic
      lineages. This methodology can be used to engineer tissue from nonautologous hESC
      sources with improved immunocompatibility.

PMID- 26218152
TI  - Operative treatment of ingrown toenail by nail fold resection without
      matricectomy.
AB  - BACKGROUND: Many operative techniques have been studied for correction of ingrown
      toenails, yet the role of nail fold resection without matricectomy is poorly
      defined. Current literature on this topic is sparse, and previous systematic
      reviews are absent. METHODS: A MEDLINE/Cumulative Index to Nursing and Allied
      Health Literature/Scopus search was performed and a systematic review was
      undertaken for articles discussing surgical treatment of ingrown toenail by nail
      fold resection without matricectomy. Outcome measures were systematically
      reported, and variations in operative technique were identified. RESULTS: Of the
      14 articles that fit the inclusion criteria, 2 were level V evidence, 11 were
      level IV, and 1 was level III. Minimum follow-up time and the criteria for a
      satisfactory outcome were not consistently defined. Recurrence rates varied from
      0% to 20%. The postsurgical infection rate was 0% for all nine studies reporting
      infection. Ten different operative techniques were identified. Three studies used
      partial or total nail avulsion as an adjunctive operative procedure. Triangular-,
      crescent-, elliptical-, semi-elliptical-, and radical-shaped skin excision
      strategies were identified. Primary and secondary intentions were used for
      closure. CONCLUSIONS: Operative algorithms for the treatment of ingrown toenail
      are still unclear regarding nail fold resection without matricectomy and are
      supported by almost entirely level IV evidence. Future prospective comparative
      studies and randomized trials are necessary to support and strengthen current
      practice.

PMID- 26218153
TI  - Effect of excessive body weight on foot arch changes in preschoolers a 2-year
      follow-up study.
AB  - BACKGROUND: A stable standing posture, and effective and aesthetic gait, depend
      heavily on correct anatomical construction of the feet, thanks to which they can
      play their important role. The shape and height of the foot arches are already
      formed in the preschool and early school years; therefore, abnormalities and
      disorders in children's feet, and correlations between foot formation and somatic
      build, are still crucial and interesting issues for orthopedists, pediatricians,
      physiotherapists, and podiatrists. This study deals with changes in the height of
      the longitudinal and transverse arches of the foot in 4- to 6-year-old children.
      METHODS: A total of 102 boys and 105 girls took part in a 24-month study in which
      their body weight, height, body mass index, and Clarke's and gamma angles were
      measured. The analysis also focused on correlations among sex, nutritional
      status, and changes in foot arch height. RESULTS: It was discovered that sex did
      not considerably affect Clarke's and gamma angle values. However, it was found
      that between ages 4 and 6 years, the proportion of overweight and obese boys and
      girls increased, and the medial longitudinal arch of the foot had a tendency to
      collapse in those with excessive body weight. The effect of nutritional status on
      the transverse arch of the foot is rather dubious. CONCLUSIONS: In light of these
      findings, therapeutic programs for preventing foot deformities in children should
      also focus on body weight control.

PMID- 26218154
TI  - Methodological quality of randomized trials published in the Journal of the
      American Podiatric Medical Association, 1999-2013.
AB  - BACKGROUND: Randomized trials must be of high methodological quality to yield
      credible, actionable findings. The main aim of this project was to evaluate
      whether there has been an improvement in the methodological quality of randomized
      trials published in the Journal of the American Podiatric Medical Association
      (JAPMA). METHODS: Randomized trials published in JAPMA during a 15-year period
      (January 1999 to December 2013) were evaluated. The methodological quality of
      randomized trials was evaluated using the PEDro scale (scores range from 0 to 10,
      with 0 being lowest quality). Linear regression was used to assess changes in
      methodological quality over time. RESULTS: A total of 1,143 articles were
      published in JAPMA between January 1999 and December 2013. Of these, 44 articles
      were reports of randomized trials. Although the number of randomized trials
      published each year increased, there was only minimal improvement in their
      methodological quality (mean rate of improvement = 0.01 points per year). The
      methodological quality of the trials studied was typically moderate, with a mean
      +/- SD PEDro score of 5.1 +/- 1.5. Although there were a few high-quality
      randomized trials published in the journal, most (84.1%) scored between 3 and 6.
      CONCLUSIONS: Although there has been an increase in the number of randomized
      trials published in JAPMA, there is substantial opportunity for improvement in
      the methodological quality of trials published in the journal. Researchers
      seeking to publish reports of randomized trials should seek to meet current best
      practice standards in the conduct and reporting of their trials.

PMID- 26218155
TI  - Introduction.

PMID- 26218156
TI  - Interprofessional podiatric surgical simulation a pilot study.
AB  - BACKGROUND: Interprofessional collaboration is key to quality outcomes in the
      health-care systems of today. Simulation is a common tool in podiatric medical
      education, and interprofessional education has become more common in podiatric
      medicine programs. Interprofessional simulation is the blending of these
      educational strategies. METHODS: A quantitative design was used to determine the
      impact of an isolated interprofessional podiatric surgical simulation between
      nurse anesthesia and podiatric medical students. RESULTS: Statistically
      significant differences were observed among participants between preintervention
      and postintervention surveys using the revised Interdisciplinary Education
      Perception Scale. CONCLUSIONS: Interprofessional simulation can be an effective
      educational opportunity for podiatric medical and nurse anesthesia students.

PMID- 26218157
TI  - The students' perspective in examining the use of high-fidelity simulators in a
      podiatric medical curriculum.
AB  - BACKGROUND: We sought to assess the perceptions that podiatric medical students
      had of the use of simulators after completing a third-year simulation rotation.
      This type of analysis has not been reported in the podiatric medicine educational
      literature. Another goal of this study was to influence the podiatric medical
      community to increase studies that help demonstrate the effectiveness of
      simulation in the podiatric medical curriculum. METHODS: Data from rotation
      evaluations of 44 students from the 2011-2012 academic year included student
      responses to 11 quantitative items and textual analysis of the students' written
      comments. Basic descriptive statistics of student responses to the quantitative
      items allowed for the analysis of central tendencies and variations. Textual
      analysis was performed on comments that were coded into themes based on similar
      properties and characteristics that the comments shared. RESULTS: The analysis
      revealed that the simulation sessions were well liked. All of the students who
      responded to the survey rated the overall simulation rotation as "superior."
      Textual analysis of the students' comments showed that students enjoy simulation
      as an educational tool because it helps enhance their clinical skills while also
      applying their didactic education to a practical experience. Clear evidence was
      presented that students want more cases and time to spend in the simulation
      laboratory to continue increasing their medical skills. CONCLUSIONS: The student
      perception of simulation is that it is an effective educational tool. Further
      testing is needed to prove simulation efficacy in a podiatric medical curriculum.

PMID- 26218158
TI  - Anatomical characteristics of the flexor digitorum accessorius longus muscle and
      their relevance to tarsal tunnel syndrome a systematic review.
AB  - BACKGROUND: Clinical and cadaver studies have reported that supernumerary muscles
      could be the etiology of a variety of pathologic disorders, such as posterior
      impingement syndrome, tarsal tunnel syndrome (TTS), and flexor hallucis longus
      tenosynovitis. We describe a unique variant of the flexor digitorum accessorius
      longus (FDAL) muscle as an apparent cause of TTS, functioning as an independent
      flexor of the second toe, which has not been described in the literature. In
      addition to this case report, a systematic review was performed of TTS caused by
      the FDAL muscle. METHODS: A targeted search of PubMed, the Cochrane Library, the
      Cumulative Index to Nursing and Allied Health Literature, and Web of Science
      identified full-text papers that fulfilled the inclusion and exclusion criteria.
      RESULTS: Twenty-nine papers were identified for inclusion in the systematic
      review: 12 clinical papers of TTS caused by the FDAL muscle and 17 cadaver-based
      papers. CONCLUSIONS: Clinicians often do not include the FDAL muscle in the
      differential diagnosis of TTS. This literature review suggests that the FDAL is
      an important muscle in terms of its functional and clinical significance.
      Knowledge of this muscle, its anatomical location and variations, and its
      magnetic resonance imaging characteristics may help clinicians make an accurate
      differential diagnosis.

PMID- 26218159
TI  - A calcified lipoma of the foot in a 100-year-old Italian woman.
AB  - Lipomas are the most common benign soft-tissue tumors found in the body. They
      tend to occur in areas of abundant adipose tissue, which explains why they are
      rarely found in the sole. Very few published cases of lipomas in the sole exist.
      When lipomas cannot be excised for histologic confirmation, ultrasonography has
      been shown to be a valuable assessment tool with high diagnostic capabilities. We
      present the case of 100-year-old patient with a long-standing plantar mass with
      late-stage clinical and sonographic features of a calcified lipoma. 

PMID- 26218160
TI  - Invasive squamous cell carcinoma with osteomyelitis of the foot a case report.
AB  - Squamous cell carcinomas are often seen on the sun-exposed areas of the skin and
      are rarely observed on the digits of the foot. However, there have been
      incidences of squamous cell carcinoma developing in the presence of chronic
      wounds with osteomyelitis, thus complicating the treatment. We present a patient
      with osteomyelitis who developed invasive squamous cell carcinoma of the third
      digit. We conclude that wounds with osteomyelitis may have underlying pathologic
      abnormalities that are not obvious on initial presentation. 

PMID- 26218161
TI  - A nonsurgical approach to arteriovenous malformation of the foot a case report.
AB  - There are few documented reports of arteriovenous malformations in the
      extremities, and even fewer specifically in the foot. Most of the documented
      cases in the foot present surgical treatments, and there is limited information
      on the nonsurgical approach. A brief review of the surgical approach to
      arteriovenous malformations in the foot and hand is presented first, followed by
      a case report of the nonsurgical treatment of an arteriovenous malformation in
      the foot, which was initially diagnosed incorrectly. 

PMID- 26218162
TI  - Esse Quam Videri in the land of rum and cigars.

PMID- 26218167
TI  - Ionic current rectification in organic solutions with quartz nanopipettes.
AB  - The study of behaviors of ionic current rectification (ICR) in organic solutions
      with quartz nanopipettes is reported. ICR can be observed even in organic
      solutions using quartz pipettes with diameters varied from several to dozens of
      nanometers, and the direction of ICR is quite different from the ICR observed in
      aqueous phase. The influences of pore size, electrolyte concentration, and
      surface charge on the ICR have been investigated carefully. Water in organic
      solutions affects the direction and extent of ICR significantly. Mechanisms about
      the formation of an electrical double layer (EDL) on silica in organic solutions
      with different amount of water have been proposed. An improved method, which can
      be employed to detect trace water in organic solutions, has been implemented
      based on Au ultramicroelectrodes with cathodic differential pulse stripping
      voltammetry. 

PMID- 26218168
TI  - Willingness to Use Pain Medication to Treat Pain.
AB  - OBJECTIVE: Despite the growth of the economic impact of pain and pain management,
      there remains a lack of knowledge about disparities, especially, evidence
      regarding individual attitudes and beliefs about accepting pain treatments. This
      study provides preliminary information on the prevalence of public concerns about
      pain management and a better understanding of factors that may ultimately lead to
      improved pain management and treatment adherence. METHODS: Using a cross
      sectional survey of community-dwelling adults 18+ in the US, 123 randomly
      selected respondents were telephone-interviewed in 2012. Principal components
      factor analysis (PCA) was used to detect statistical groupings of attitudes and
      beliefs about pain and pain management. The modified Protection Motivation Theory
      was applied to examine the willingness to use pain medicine. RESULTS: The five
      most important components pertained to threat appraisal, coping appraisal,
      attitudes, subjective norms, and perceived control. Threat appraisal was the most
      common factor, and subjective norms was the least common factor. Lower income,
      more awareness of hospice, and less misconceptions about threat appraisal and
      attitudes toward pain and pain management were associated with more willingness
      to use pain medicine in hierarchical regression. CONCLUSIONS: These components
      are useful for future research on the willingness to use pain medicine and may
      have implications for assessing cognitive barriers toward pain and pain
      management among the general public.

PMID- 26218169
TI  - Melting Temperature Mapping Method: A Novel Method for Rapid Identification of
      Unknown Pathogenic Microorganisms within Three Hours of Sample Collection.
AB  - Acquiring the earliest possible identification of pathogenic microorganisms is
      critical for selecting the appropriate antimicrobial therapy in infected
      patients. We herein report the novel "melting temperature (Tm) mapping method"
      for rapidly identifying the dominant bacteria in a clinical sample from sterile
      sites. Employing only seven primer sets, more than 100 bacterial species can be
      identified. In particular, using the Difference Value, it is possible to identify
      samples suitable for Tm mapping identification. Moreover, this method can be used
      to rapidly diagnose the absence of bacteria in clinical samples. We tested the Tm
      mapping method using 200 whole blood samples obtained from patients with
      suspected sepsis, 85% (171/200) of which matched the culture results based on the
      detection level. A total of 130 samples were negative according to the Tm mapping
      method, 98% (128/130) of which were also negative based on the culture method.
      Meanwhile, 70 samples were positive according to the Tm mapping method, and of
      the 59 suitable for identification, 100% (59/59) exhibited a "match" or "broad
      match" with the culture or sequencing results. These findings were obtained
      within three hours of whole blood collection. The Tm mapping method is therefore
      useful for identifying infectious diseases requiring prompt treatment. 

PMID- 26218170
TI  - Magnetically Actuated Single-Walled Carbon Nanotubes.
AB  - We couple magnetic tweezer techniques with standard lithography methods to make
      magnetically actuated single-walled carbon nanotube (SWNT) devices. Parallel
      arrays of 4-10 MUm-long SWNT cantilevers are patterned with one end anchored to
      the substrate and the other end attached to a micron-scale iron magnetic tag that
      is free to move in solution. Thermal fluctuations of this tag provide a direct
      measurement of the spring constant of the SWNT cantilevers, yielding values of
      10(-7)-10(-8) N/m. This tag is also a handle for applying forces and torques
      using externally applied magnetic field gradients. These techniques provide a
      platform on which interaction forces between SWNTs and other objects such as
      biomolecules and cells can be measured in situ. 

PMID- 26218171
TI  - Laparoscopic Resection of Retroperitoneal Paragangliomas: A Comparison with
      Conventional Open Surgical Procedures.
AB  - OBJECTIVE: Paraganglioma (PGL) is a rare type of tumor that arises from the extra
      adrenal paraganglia. Laparoscopic adrenalectomy is well established for the
      treatment of adrenal pheochromocytomas, but laparoscopic resection of PGLs is
      controversial. In this study, we compared the clinical outcomes of laparoscopic
      and conventional open surgical procedures for PGLs. We also analyze the safety
      and feasibility of laparoscopic technique for renal hilar PGLs. METHODS: A
      retrospective review of all patients who underwent resection of retroperitoneal
      PGLs from 2002 to 2014 in our hospital was performed. Twelve patients underwent
      open procedures, and 15 underwent laparoscopic procedures. The preoperative,
      intraoperative, and postoperative data were collected and analyzed. RESULTS: PGLs
      located at the renal hilum were predominantly both in the Lap group (n = 9) and
      open group (n = 7). Laparoscopic procedures in 14 of 15 patients were effectively
      completed without conversion to open surgery; one case with renal hilar tumor was
      converted to open surgery because of bleeding. The baseline characteristic of the
      patients in each group was well equivalent with respect to patient age, gender,
      body mass index, and tumor size. In the Lap group, the perioperative indexes were
      significantly different from those of the open group (each p < 0.05), including
      operative time (217.36 +/- 51.90 vs 175.67 +/- 36.79; p = 0.029), estimated blood
      loss (80.71 +/- 83.52 vs 172.50 +/- 160.86 mL; p = 0.047), and postoperative
      hospital stay (5.64 +/- 1.95 vs 8.58 +/- 1.97 days; p = 0.001). However, the
      intraoperative hemodynamic parameters and intensive care unit stay days were
      similar in both the groups. The perioperative data of the two procedures for
      renal hilar PGLs were compared. The Lap group showed estimated blood loss, and
      postoperative hospital stay outcomes were more favorable than the open group.
      Other data were similar in both the groups. CONCLUSION: Laparoscopic procedure is
      safe and feasible in the treatment of patients with retroperitoneal PGLs.
      Laparoscopic resection of PGLs from the renal hilum is technically challenging.
      However, it is possible to safely undertake laparoscopic resection of these
      tumors by an experienced surgeon.

PMID- 26218172
TI  - Detection of heart beats in multimodal data: a robust beat-to-beat interval
      estimation approach.
AB  - The heart rate and its variability play a vital role in the continuous monitoring
      of patients, especially in the critical care unit. They are commonly derived
      automatically from the electrocardiogram as the interval between consecutive
      heart beat. While their identification by QRS-complexes is straightforward under
      ideal conditions, the exact localization can be a challenging task if the signal
      is severely contaminated with noise and artifacts. At the same time, other
      signals directly related to cardiac activity are often available. In this multi
      sensor scenario, methods of multimodal sensor-fusion allow the exploitation of
      redundancies to increase the accuracy and robustness of beat detection.In this
      paper, an algorithm for the robust detection of heart beats in multimodal data is
      presented. Classic peak-detection is augmented by robust multi-channel,
      multimodal interval estimation to eliminate false detections and insert missing
      beats. This approach yielded a score of 90.70 and was thus ranked third place in
      the PhysioNet/Computing in Cardiology Challenge 2014: Robust Detection of Heart
      Beats in Muthmodal Data follow-up analysis.In the future, the robust beat-to-beat
      interval estimator may directly be used for the automated processing of
      multimodal patient data for applications such as diagnosis support and
      intelligent alarming. 

PMID- 26218173
TI  - Paediatric obesity: can medications help.
AB  - PURPOSE OF REVIEW: The purpose of this study is to review current and emergent
      antiobesity drugs in paediatrics. RECENT FINDINGS: Understanding of the
      pathophysiology of obesity is improving, but access to antiobesity drugs
      continues to be challenging, especially in paediatrics. Few antiobesity drug
      trials have been conducted in paediatrics and postmarketing findings remain a
      source of concern. New approaches by the European Medicines Agency and the US
      Food and Drug Administration have provided guidance for the development of
      antiobesity drugs. However, few are in the pipeline and high-quality trials in
      paediatrics are lacking. SUMMARY: We are providing a summary of available
      antiobesity drug therapies, barriers to treatment and emerging pharmacotherapies.

PMID- 26218174
TI  - OMIP-028: activation panel for Rhesus macaque NK cell subsets.

PMID- 26218175
TI  - Primary gastric choriocarcinoma: A rare case.
AB  - INTRODUCTION: Primary gastric choriocarcinoma accounts for 0.08% of all gastric
      cancers. It is a rapidly growing, widely metastatic and beta-HCG-producing tumour
      of trophoblastic cells. PRESENTATION OF CASE: A 69-year-old white man presented
      to the hospital with symptomatic anaemia. An upper gastrointestinal endoscopy
      showed an ulcer of the cardia and lesser curvature, whose biopsy specimens proved
      to be malignant (carcinoma cells, non-specified). The patient underwent total
      gastrectomy with D2 lymphadenectomy. A histologic evaluation revealed a
      choriocarcinoma admixed with adenocarcinoma cells without lymph node metastases.
      The patient died from haemorrhagic shock, due to rupture of liver metastases and
      a massive haemoperitoneum, within 2 months of the initial presentation.
      DISCUSSION: Primary gastric choriocarcinoma characteristics resemble those of
      gastric primary adenocarcinoma. The dedifferentiation theory is the most widely
      accepted theory to explain the pathogenesis of PGC. It is essential to rule out
      other possible primary lesions such as testicular tumour. The optimal treatment
      is not yet well established due to very few reported cases. CONCLUSION: Primary
      gastric choriocarcinoma is a rare tumour with an aggressive behaviour and very
      poor prognosis.

PMID- 26218176
TI  - Bilateral synchronous low-grade adenosquamous carcinoma of the breast: A Case
      report with review of the current literature.
AB  - INTRODUCTION: Low-grade adenosquamous carcinoma (LGASC) is a rare, unique variant
      of metaplastic breast carcinoma, characterized by clinical indolence and low
      grade cytomorphology. Being clinically asymptomatic with indefinite imaging
      characteristics, diagnosis is solely dependent on histopathology. PRESENTATION OF
      CASE: A 68-year-old woman presented to the Breast Health Center with mammogram
      detected left-sided retroareolar calcifications. She had a three-year history of
      non-progressive bilateral nipple inversion, and was otherwise asymptomatic. Left
      breast biopsy revealed atypical metaplastic squamous epithelial cells.
      Subsequently a wire-guided lumpectomy diagnosed a syringomatous adenoma of the
      nipple. A surveillance MRI identified a contralateral breast lesion, which on
      core biopsy showed an atypical adenosquamous lesion. Bilateral central
      mastectomies with bilateral sentinel node biopsies were undertaken.
      Histopathological review of both breast specimens confirmed the unique features
      of adenosquamous carcinoma identified by an infiltrative pattern of small rounded
      compressed angulated glands with squamous differentiation and low-grade
      cytomorphology. The tumors were triple negative [ER, PR, HER2]. The sentinel
      lymph nodes were negative. CONCLUSION: Bilateral synchronous LGASC of the breasts
      is exceedingly uncommon and remains a diagnostic and therapeutic challenge.
      Despite being triple negative, due to its indolent behavior, recognition of this
      unusual primary breast malignancy is important as it has a more favorable
      prognosis. Yet, due to its rarity, there are no guidelines for best practice
      management regarding the role of adjuvant therapy.

PMID- 26218177
TI  - Inferiorly based buccinator myomucosal island flap in oral and pharyngeal
      reconstruction. Four techniques to increase its application.
AB  - INTRODUCTION: Reconstruction of oral and pharyngeal defects after pathologic
      resections with the same tissue is an optimal and ideal target. Islanded variety
      of inferiorly pedicled facial artery musculomucosal flap, in which facial artery
      and vein are skeletonized (referred to as inferiorly based BUMIF), is suitable
      for reconstruction of medium-sized mucosal defects. PRESENTATION OF CASES: In
      this article, with four cases, modifications of this flap are demonstrated in
      reconstruction of large intraoral and oropharyngeal defects and coverage of
      alveolar ridge in the mandible. DISCUSSION: In some situations, there is a need
      for more mucosal paddle, longer vascular pedicle and more adaptation to the
      recipient bed. CONCLUSION: Relocating Stensen's duct increases the mucosal paddle
      with cranial extension of superior limit while differential incision of the
      mucosa and buccinator muscle in mandibular vestibule extend the lower limit of
      this flap. Bone suture is a good complementary technique when this flap is used
      for coverage of mandibular alveolar ridge. Inferiorly based BUMIF with added
      length is indicated for oropharyngeal and contralateral mouth floor
      reconstructions.

PMID- 26218178
TI  - Inferring other people's states of mind: Comparison across social anxiety, body
      dysmorphic, and obsessive-compulsive disorders.
AB  - BACKGROUND: Social anxiety disorder (SAD) and body dysmorphic disorder (BDD) are
      characterized by fears of negative evaluation by others (related to one's own
      incompetence or flawed appearance, respectively). Previous research has shown
      that individuals with SAD and BDD exhibit difficulty identifying facial
      expressions and interpretive biases for threat in social situations. The current
      study aimed at further investigating social cognition in SAD, BDD, and mentally
      healthy controls (35 individuals per group, respectively). Further, 35
      individuals with obsessive-compulsive disorder (OCD) as a clinical control group
      not characterized by evaluation fears were included. METHODS: The Movie for the
      Assessment of Social Cognition (MASC) was applied. It consists of 45 video
      sequences depicting interactions among four people at a dinner party.
      Participants are instructed to evaluate each scenario with respect to the
      characters' emotions, thoughts, and intentions from a bystander perspective (i.e.
      other-referent context). RESULTS: Only the socially anxious groups (SAD and BDD)
      were overall less accurate than the other groups in correctly interpreting the
      social situations, whereas no difference was obtained between the OCD and the
      control group. Further analyses indicated that the SAD and BDD groups were less
      accurate in identifying other people's thoughts and intentions, whereas, again,
      no difference was observed between the OCD and control groups. In addition, the
      SAD group was less accurate in inferring thoughts and intentions than the OCD
      group. Interestingly, the groups did not differ with respect to identifying other
      people's emotions. CONCLUSIONS: These results mostly confirm existing cognitive
      behavioral models of SAD and BDD emphasizing that biased interpretation of what
      others think or intend is one of the key factors maintaining social anxiety and
      appearance-related concerns. Our study shows that this bias generalizes to social
      situations in which individuals take a third-person observer perspective.

PMID- 26218179
TI  - Leptin Effect on Acetylation and Phosphorylation of Pgc1alpha in Muscle Cells
      Associated With Ampk and Akt Activation in High-Glucose Medium.
AB  - Leptin is crucial in energy metabolism, including muscle regulation. Peroxisome
      proliferator activated receptor gamma co-activator 1alpha (PGC1alpha)
      orchestrates energy metabolism and is tightly controlled by post-translational
      covalent modifications such as phosphorylation and acetylation. We aimed to
      further the knowledge of PGC1alpha control by leptin (at physiological levels) in
      muscle cells by time-sequentially analysing the activation of AMP activated
      protein kinase (AMPK), P38 mitogen-activated protein kinase (P38 MAPK) and Akt
      (Protein kinase B)--all known to phosphorylate PGC1alpha and to be involved in
      the regulation of its acetylation status--in C2C12 myotubes placed in a high
      glucose serum-free medium. We also studied the protein levels of PGC1alpha,
      Sirtuin 1, adiponectin, COX IV, mitofusin 2 (Mfn2), and pyruvate dehydrogenase
      kinase 4 (PDK4). Our main findings suggest an important role of leptin regulating
      AMPK and Akt phosphorylation, Mfn2 induction and PGC1alpha acetylation status,
      with the novelty that the latter in transitorily increased in response to leptin,
      an effect dependent, at least in part, on AMPK regulation. These post
      translational reversible changes in PGC1alpha in response to leptin, especially
      the increase in acetylation status, may be related to the physiological role of
      the hormone in modulating muscle cell response to the physiological/nutritional
      status.

PMID- 26218180
TI  - Impact of telemedicine support by remote pre-hospital electrocardiogram on
      emergency medical service management of subjects with suspected acute
      cardiovascular disease.

PMID- 26218181
TI  - Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive
      pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is independently associated with an
      increased burden of cardiovascular disease. Besides coronary artery disease (CAD)
      and congestive heart failure (CHF), specific electrocardiographic (ECG)
      abnormalities and cardiac arrhythmias seem to have a significant impact on
      cardiovascular prognosis of COPD patients. Disturbances of heart rhythm include
      premature atrial contractions (PACs), premature ventricular contractions (PVCs),
      atrial fibrillation (AF), atrial flutter (AFL), multifocal atrial tachycardia
      (MAT), and ventricular tachycardia (VT). Of note, the identification of ECG
      abnormalities and the evaluation of the arrhythmic risk may have significant
      implications in the management and outcome of patients with COPD. This article
      provides a concise overview of the available data regarding ECG abnormalities and
      arrhythmias in these patients, including an elaborated description of the
      underlying arrhythmogenic mechanisms. The clinical impact and prognostic
      significance of ECG abnormalities and arrhythmias in COPD as well as the
      appropriate antiarrhythmic therapy and interventions in this setting are also
      discussed.

PMID- 26218182
TI  - Significant left hemothorax after transapical closure of cardiac apex with
      minithoracotomy and transapical transcatheter prosthetic mitral paravalvular leak
      closure.

PMID- 26218183
TI  - Predictive factors of lead failure in patients implanted with cardiac devices.
AB  - INTRODUCTION: Lead failures (LFs) are one of the most common complications in
      patients implanted with cardiovascular implantable electronic devices. LFs often
      cause serious secondary complications such as inappropriate ICD shocks or
      asystole. This study aimed to identify the clinical factors associated with the
      occurrence of LFs. METHODS: A total of 735 consecutive device implantations (mean
      age 67+/-15years, males 64%) performed at a single university hospital setting
      from 1997 to 2014 were included. The implanted devices consisted of 421
      pacemakers, 250 implantable cardioverter defibrillators (ICD), 9 cardiac
      resynchronization therapy pacemakers (CRT-P), and 55 CRT defibrillators (CRT-D).
      The primary endpoint was the development of an LF. RESULTS: During a mean
      duration of 5.8+/-4.3years, 38 LFs developed in 31 patients (mean age 56+/
      14years). LFs included 32 ICD (7 Sprint Fidelis, 2 Riata), and 6 pacing leads.
      Nine patients received inappropriate ICD shocks and 1 had syncope due to an LF.
      All patients underwent lead reinsertions with device replacements. Eight patients
      required opposite site implantations due to venous occlusions. The predictive
      factors of LFs were the age, male sex, taller body length, ICD vs. pacemaker,
      lesser lead number, extra-thoracic puncture of the axillary vein vs. a cut-down
      of the cephalic vein, use of recalled leads and patients with idiopathic
      ventricular fibrillation (IVF) and Brugada syndrome (BrS). CONCLUSION: LFs
      occurred mainly with ICD leads. A lesser age, the puncture method, lead model,
      and diagnosis of IVF/BrS were associated with the development of LFs.

PMID- 26218184
TI  - A "black June" for Chinese medical workers.

PMID- 26218185
TI  - Potential of biohydrogen production from organic fraction of municipal solid
      waste (OFMSW) using pilot-scale dry anaerobic reactor.
AB  - A long-term evaluation of a mesophilic up-flow intermittently stirred tank
      reactor (UISTR) for hydrogen production from the organic fraction of municipal
      solid waste was investigated. UISTR was operated at five different hydraulic
      retention times (HRTs) of 10, 7.5, 5, 3 and 2days. This corresponds to organic
      loading rates (OLRs) of 18.1, 26.2, 41.3, 61.0, and 97.2gCOD/L/day, respectively.
      The highest volumetric H2 production of 2.20+/-0.19L/L/d and H2 yield of 2.05+/
      0.33molH2/molCarbohydrate were achieved at HRT of 3days and OLR of
      61.0gCOD/L/day. This revealed a higher sCOD/tCOD ratio of 0.46+/-0.08 and a lower
      particle size diameter of 307.6MUm in the digestate, with a reduction of 72.0%.
      The maximum carbohydrates, proteins, and lipids conversions amounted to 68.2+/
      13.0%, 37.5+/-6.7% and 48.6+/-4.7%, respectively recorded at HRT of 10days and
      OLR of 18.1gCOD/L/day.

PMID- 26218186
TI  - Chronic neutrophilic leukaemia and plasma cell-related neutrophilic leukaemoid
      reactions.
AB  - Many cases reported as 'chronic neutrophilic leukaemia' have had an associated
      plasma cell neoplasm. Recent evidence suggests that the great majority of such
      cases represent a neutrophilic leukaemoid reaction to the underlying multiple
      myeloma or monoclonal gammopathy of undetermined significance. We have analysed
      all accessible reported cases to clarify the likely diagnosis and to ascertain
      whether toxic granulation, Dohle bodies and an increased neutrophil alkaline
      phosphatase score were useful in making a distinction between chronic
      neutrophilic leukaemia and a neutrophilic leukaemoid reaction. We established
      that all these changes occur in both conditions. Toxic granulation and Dohle
      bodies are more consistently present in leukaemoid reactions but also occur quite
      frequently in chronic neutrophilic leukaemia. The neutrophil alkaline phosphatase
      score is increased in both conditions and is of no value in making a distinction.

PMID- 26218187
TI  - Segmented Highly Branched Copolymers: Rationally Designed Macromolecules for
      Improved and Tunable (19)F MRI.
AB  - Highly branched polymers are a promising platform for the design of next
      generation contrast agents for (19)F magnetic resonance imaging (MRI). A series
      of segmented highly branched polymers (SHBPs) consisting of fluoro- and PEG-based
      monomers were synthesized by self-condensing vinyl copolymerization (SCVP) using
      the reversible addition-fragmentation chain transfer (RAFT) technique. SHBPs
      having different compositions and degrees of branching were obtained by varying
      the monomer type and feed ratio of monomer to chain transfer agent (CTA). The
      chemical structures and physical properties of the branched polymers were
      thoroughly characterized in detail by NMR, SEC and DSC. The systematic variation
      in structural parameters allowed the relationships between molecular structure,
      sequence distribution, and imaging performance to be examined. The (19)F NMR
      properties were strongly affected by the sequence distribution of the fluorinated
      monomers, the type of polymer backbone and the degree of branching. As a result,
      SHBPs consisting of statistical copolymeric segments of acrylate units were
      identified as excellent candidates for imaging due to a single (19)F signal, long
      T2 relaxation times, and high fluorine contents. The SHBPs could be all imaged or
      selectively imaged by taking advantage of the differences in relaxation times,
      demonstrating tunable and selective imaging performance through tailoring the
      structure and composition of the SHBPs. 

PMID- 26218190
TI  - Cathodic Voltammetric Behavior of Pillar[5]quinone in Nonaqueous Media. Symmetry
      Effects on the Electron Uptake Sequence.
AB  - The cathodic voltammetric behavior of pillar[5]quinone was investigated in
      dichloromethane solution. Our data show that the symmetry of the macrocycle has a
      pronounced effect on the electron uptake sequence. The uptake of the first five
      electrons follows a 2-1-2 pattern, and only a total of eight electrons could be
      injected into the macrocycle under our experimental conditions. 

PMID- 26218188
TI  - Measurement of Scleral Thickness in Humans Using Anterior Segment Optical
      Coherent Tomography.
AB  - Anterior segment optical coherent tomography (AS-OCT, Visante; Zeiss) is used to
      examine meridional variation in anterior scleral thickness (AST) and its
      association with refractive error, ethnicity and gender. Scleral cross-sections
      of 74 individuals (28 males; 46 females; aged between 18-40 years (27.7+/-5.3))
      were sampled twice in random order in 8 meridians: [superior (S), inferior (I),
      nasal (N), temporal (T), superior-temporal (ST), superior-nasal (SN), inferior
      temporal (IT) and inferior-nasal (IN)]. AST was measured in 1mm anterior-to
      posterior increments (designated the A-P distance) from the scleral spur (SS)
      over a 6mm distance. Axial length and refractive error were measured with a Zeiss
      IOLMaster biometer and an open-view binocular Shin-Nippon autorefractor. Intra-
      and inter-observer variability of AST was assessed for each of the 8 meridians.
      Mixed repeated measures ANOVAs tested meridional and A-P distance differences in
      AST with refractive error, gender and ethnicity. Only right eye data were
      analysed. AST (mean+/-SD) across all meridians and A-P distances was 725+/-46
      MUm. Meridian SN was the thinnest (662+/-57 MUm) and I the thickest (806+/-60
      MUm). Significant differences were found between all meridians (p<0.001), except
      S:ST, IT:IN, IT:N and IN:N. Significant differences between A-P distances were
      found except between SS and 6 mm and between 2 and 4 mm. AST measurements at 1mm
      (682+/-48 MUm) were the thinnest and at 6mm (818+/-49 MUm) the thickest
      (p<0.001); a significant interaction occurred between meridians and A-P distances
      (p<0.001). AST was significantly greater (p<0.001) in male subjects but no
      significant differences were found between refractive error or ethnicity.
      Significant variations in AST occur with regard to meridian and distance from the
      SS and may have utility in selecting optimum sites for pharmaceutical or surgical
      intervention.

PMID- 26218189
TI  - Ethnic differences in types of social support from multiple sources after breast
      cancer surgery.
AB  - OBJECTIVES: Diagnosis of and treatment for breast cancer (BCa) may require
      psychological adaptation and often involve heightened distress. Several types of
      social support positively relate to psychological adaptation to BCa, and negative
      support is associated with poorer adaptation. Although Hispanic women report
      greater distress than non-Hispanic White (NHW) women after diagnosis of BCa, no
      studies have examined ethnic differences in types of social support received from
      varying sources after surgery for BCa. DESIGN: Hispanic (N = 61) and NHW (N =
      150) women diagnosed with early-stage BCa self-reported emotional, informational,
      instrumental, and negative support from five sources. Ethnic differences in
      levels of social support were compared using multiple regression analysis.
      RESULTS: When controlling for age, income, days since surgery, and stage of
      disease in multivariable models there were no ethnic differences in levels of
      emotional support from any source. Hispanic women reported greater informational
      support from adult women family members and children and male adult family
      members than did NHW women. Instrumental support from adult women family members
      was also greater among Hispanic than NHW women. Hispanic women reported higher
      negative support from husbands/partners and from children and male adult family
      members. When the number of years in the USA was controlled, Hispanic women
      showed greater informational support from adult women family members, children
      and male adult family members, and friends. Instrumental support from adult women
      family members remained greater in Hispanic women, but negative support no longer
      differed. CONCLUSION: Family is a greater source of informational and
      instrumental support for Hispanic than NHW women. Hispanic women reported higher
      negative support from male sources than did NHW women. Level of support from
      different sources may also depend on time spent in the USA. Longitudinal studies
      are needed to determine whether patterns and sources of social support shift over
      the course of BCa treatment.

PMID- 26218191
TI  - Predicting Dissolved Inorganic Carbon in Photoautotrophic Microalgae Culture via
      the Nitrogen Source.
AB  - Dissolved inorganic carbon (DIC) and pH are key factors that control the growth
      rate of microalgae growing photoautotrophically. Being able to quantify how DIC
      and pH independently affect growth kinetics requires a means to control each
      parameter independently. In this study, we used the Proton Condition (PC) to
      develop means to control pH and DIC independently. Using the PC, we found that
      different N sources systematically affect the alkalinity and the DIC in distinct
      ways. With pH controlled at a fixed level by CO2 addition, using nitrate as the N
      source increased the alkalinity and DIC concentration in proportion to the
      increase in biomass concentration. In contrast, using ammonium caused the
      alkalinity and DIC to decline, while using ammonium nitrate left the DIC nearly
      unchanged. Experiments with a model photoautotroph cyanobacterium, Synechocystis
      sp. PCC 6803, in batch experiments with modified BG-11 media and a pH-stat
      confirmed all of the DIC predictions of the PC-based model. Thus, this study
      provides a mechanistic basis for managing the DIC for photoautotrophic cultures
      through the N source. In particular, using ammonium nitrate makes it possible to
      control DIC and pH independently in a pH-stat.

PMID- 26218192
TI  - Encapsulated Guests in the Smallest Spaces: Shrinking Guests by Compression and
      Investigations under Solvent-Free Conditions.
AB  - Noncovalent interactions play a pivotal role in a variety of biological and
      chemical processes. The experimental determination and quantum chemical
      calculations of the forces driving these interactions are of utmost importance.
      Of special interest are interactions of molecules in small spaces which show
      phenomena different from conventional behavior in solution. An extension is the
      encapsulation of guests in smallest spaces: The guests are too large to be
      included under standard conditions and hence must be forced to intrude into the
      cavity. Here, we show the design of such a host-guest system which allows to
      directly compare the measured thermodynamic values to gas-phase quantum chemical
      calculations. Structural investigation of the complexes reveals that the
      encapsulation process causes not only an extension of the hollow space of the
      host but also a shrinking of the included guest by compression. 

PMID- 26218193
TI  - Characterization of Pseudomonas chlororaphis from Theobroma cacao L. rhizosphere
      with antagonistic activity against Phytophthora palmivora (Butler).
AB  - AIM: To isolate and characterize rhizobacteria from Theobroma cacao with
      antagonistic activity against Phytophthora palmivora, the causal agent of the
      black pod rot, which is one of the most important diseases of T. cacao. METHODS
      AND RESULTS: Among 127 rhizobacteria isolated from cacao rhizosphere, three
      isolates (CP07, CP24 and CP30) identified as Pseudomonas chlororaphis, showed in
      vitro antagonistic activity against P. palmivora. Direct antagonism tested in
      cacao detached leaves revealed that the isolated rhizobacteria were able to
      reduce symptom severity upon infection with P. palmivora Mab1, with Ps.
      chlororaphis CP07 standing out as a potential biocontrol agent. Besides, reduced
      symptom severity on leaves was also observed in planta where cacao root system
      was pretreated with the isolated rhizobacteria followed by leaf infection with P.
      palmivora Mab1. The production of lytic enzymes, siderophores, biosurfactants and
      HCN, as well as the detection of genes encoding antibiotics, the formation of
      biofilm, and bacterial motility were also assessed for all three rhizobacterial
      strains. By using a mutant impaired in viscosin production, derived from CP07, it
      was found that this particular biosurfactant turned out to be crucial for both
      motility and biofilm formation, but not for the in vitro antagonism against
      Phytophthora, although it may contribute to the bioprotection of T. cacao.
      CONCLUSIONS: In the rhizosphere of T. cacao, there are rhizobacteria, such as Ps.
      chlororaphis, able to protect plants against P. palmivora. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study provides a theoretical basis for the potential
      use of Ps. chlororaphis CP07 as a biocontrol agent for the protection of cacao
      plants from P. palmivora infection.

PMID- 26218194
TI  - Seed-free synthesis of 1D silver nanowires ink using clove oil (Syzygium
      Aromaticum) at room temperature.
AB  - HYPOTHESIS: Silver nanowires (AgNWs) have been demonstrated to be a promising
      next generation conducting material and an alternative to the traditional
      electrode (ITO) because of its high conductivity, transparency and stability.
      Generally, AgNWs are synthesized by chemical method (mainly polyol reduction
      method) at high temperature in the presence of exotic seeds. The present work
      aims at the green approach for preparation and characterization of 1D AgNWs ink
      using clove oil (Syzygium Aromaticum) at room temperature. EXPERIMENTS: AgNWs was
      prepared by green synthesis using clove oil as reducing as well as capping agent
      at room temperature. The obtained ink was purified, filtered and redissolved in
      methanol. FINDINGS: The prepared AgNWs showed an absorption peaks at 350 and
      387nm in the UV-vis spectrum due to transverse SPR mode of silver. From the HR
      TEM analysis, it was observed that the AgNWs possess an average diameter and
      length of ~39+/-0.01nm and ~3MUm, respectively. The obtained AgNWs are
      crystalline in nature and are arranged in a perfect crystal lattice orientation,
      which was confirmed from the selected area electron diffraction studies.
      Moreover, the X-ray diffraction analysis confirms the face centered cubic
      structure. The AgNWs coated glass substrate shows an electrical conductivity of
      ~0.48*10(6)S/m.

PMID- 26218195
TI  - Insights into the synthesis of layered double hydroxide (LDH) nanoparticles: Part
      2. Formation mechanisms of LDH.
AB  - This study demonstrates the effect of (co)intercalated anion compositions on
      nanostructure evolution to understand the formation mechanisms of layered double
      hydroxide (LDH) nanoparticles following coprecipitation and hydrothermal
      treatments (HT). Initially, the room temperature coprecipitation resulted in
      amorphous primary nanoparticles that agglomerated at the edges due to low surface
      charge densities. The reversibility of such agglomeration was determined by the
      crystalline quality upon HT and consequent surface charge density, which in turn
      were strongly influenced by the composition of the intercalated anions. Upon
      crystallization, the agglomerated Zn2Al(OH)6(NO3)0.3(CO3)0.35?xH2O primary
      nanoparticles re-dispersed, but the Zn2Al(OH)6(NO3)?xH2O nanoparticles with much
      lower stability and higher disorder (especially at the edges) exhibited
      irreversible agglomeration, and transformed into secondary nanoparticles via
      aggregational growth. Additionally, the stability studies on
      Zn2Al(OH)6(NO3)y(CO3)0.5(1-y)?xH2O nanoparticles (y=0-1) showed that the size
      difference between the cointercalated anions caused phase separation when
      0.9?y?0.6, leading to bimodal size distributions. Moreover, the coarsening rates
      were controlled through the cointercalated anion compositions. By gradually
      varying the ratio of cointercalated NO3(-) to CO3(2-), monodispersed
      Zn2Al(OH)6(NO3)y(CO3)0.5(1-y)?xH2O (0.5?y?0) nanoparticles with systematic
      variation in the particle size of ~200-400nm were obtained after HT at 85 degrees
      C for 12h. 

PMID- 26218196
TI  - Synthesis, kinetics and photocatalytic study of "ultra-small" Ag-NPs obtained by
      a green chemistry method using an extract of Rosa 'Andeli' double delight petals.
AB  - This paper reports the effect of different concentrations of Rosa 'Andeli' double
      delight petals aqueous extract (PERA) in the synthesis of silver nanoparticles
      (Ag-NPs), using an easy green chemistry method. Its kinetics study and
      photocatalytic activity were also evaluated. The Ag-NPs were obtained using an
      aqueous silver nitrate solution (AgNO3) with 9.66% w/v, 7.25% w/v, and 4.20% w/v
      PERA as both reducing-stabilizing agent. The formation of the Ag-NPs was
      demonstrated by analysis of UV-vis spectroscopy, scanning electron microscopy
      energy dispersive spectroscopy (SEM-EDS) and transmission electron microscopy
      (TEM). TEM analysis shows spherical nanoparticles in shape and size between ~0.5
      and 1.4nm. A comparative study was done to determine which concentration was the
      best reducing-stabilizing agent, and we found out that "ultra-small"
      nanoparticles (0.5-1.1nm) were obtained with 9.66% w/v of PERA. The size of the
      Ag-NPs depends on the concentration of PERA and Ag(I). The reaction of formation
      of "ultra-small" Ag-NPs, proved to be first order for metallic precursor (silver)
      and second order for reducing-stabilizing agent (PERA). The Ag-NPs showed
      photocatalytic activity, in degradation of commercial dye with an efficiency of
      95%. 

PMID- 26218197
TI  - Characterization of oligosaccharide-functionalized hyperbranched poly(ethylene
      imine) and their complexes with retinol in aqueous solution.
AB  - Structure, internal density distribution, and size of hyperbranched poly(ethylene
      imine) (PEI) functionalized with various amounts of maltose (PEI-Mal) in
      phosphate buffer were studied by small angle X-ray scattering (SAXS) and dynamic
      light scattering (DLS). The value of pH was varied in the range from 3 to 9.
      Virtually no effect of pH on the nanostructure was found in this interval. The
      SAXS results revealed a broad segmental radial density distribution, i.e. a
      "fluffy" globular structure rather than a distinct core-shell structure with a
      high-density compact core and a low-density corona. This suggests that the
      maltose units are rather evenly distributed both in the interior and on the
      surface of the species with a PEI-core of molar mass of 25,000g/mol. The DLS
      measurements showed that the overall size of the PEI-Mal derivatives increased as
      the number of maltose units in the PEI-Mal structures rises. The interaction of
      the hydrophobic model drug retinol with PEI or PEI-Mal derivatives was also
      investigated. The UV-visible spectroscopy results disclosed that the solubility
      of retinol in the phosphate buffer is very poor and it takes a very long time to
      solubilize retinol. Moreover, retinol induces aggregation of dendritic
      glycopolymers where the growth of aggregates occurs continuously over several
      days and then remains virtually constant. 

PMID- 26218198
TI  - Photoisomerization-induced morphology and transparency transition in an
      azobenzene based two-component organogel system.
AB  - A two-component gel containing long chain alkylated gallic acid (GA) and
      photochromic phenazopyridine (PAP) was prepared. The gel was thoroughly
      characterized by UV-visible and IR spectra, SEM and POM images, XRD diffraction
      and dynamic oscillatory measurements. The structure and transparency of the two
      component gel can be reversibly changed by alternative UV light irradiation and
      warming in the palm of the hand. This kind of soft material has potential
      application in upscale surface functional materials. 

PMID- 26218199
TI  - A significant cathodic shift in the onset potential and enhanced
      photoelectrochemical water splitting using Au nanoparticles decorated WO3 nanorod
      array.
AB  - Au nanoparticles decorated WO3 nanorod array was prepared and applied for solar
      water oxidation. Scanning electron microscopy and transmission electron microscop
      images showed that Au distributed on the surface of WO3 nanorod array. The
      surface plasmon resonance effect of Au nanoparticles contributed to the
      enhancement of photoelectrochemical performance of Au-WO3 photoanode, such as
      enhanced photocurrent density of 1.17mA/cm(2) at 1.0V vs Ag/AgCl, a cathodic
      shift of onset of ~0.2V and higher stability. UV-vis absorption, electrochemical
      impedance and Mott-Schottky measurements proved that Au-WO3 photoanode has
      enhanced light absorption, lower transfer resistance, increased photogenerated
      carriers density and higher hole injection yield. Therefore, Au-WO3 photoanode
      exhibited higher photoelectrochemical performance than WO3 photoanode. 

PMID- 26218200
TI  - The drainage of foamy granular suspensions.
AB  - Foam-based materials are promising micro-structured materials with interesting
      thermal and acoustical properties. The control of the material morphology
      requires counteracting all the destabilizing mechanisms during their production,
      starting with the drainage process, which remains to be understood in the case of
      the complex fluids that are commonly used to be foamed. Here we perform
      measurements for the drainage velocity of aqueous foams made with granular
      suspensions of hydrophilic monodisperse particles and we show that the effect of
      the particles can be accounted by two parameters: the volume fraction of
      particles in the suspension (phip) and the confinement parameter (lambda), that
      compares the particle size to the size of passage through constrictions in the
      foam network. We report data over wide ranges for those two parameters and we
      identify all the regimes and transitions occurring in the phip-lambda diagram. In
      particular, we highlight a transition which refers to the included/excluded
      configuration of the particles with respect to the foam network, and makes the
      drainage velocity evolve from its minimal value (fully included particles) to its
      maximal one (fully excluded particles). We also determine the conditions
      (phip,lambda) leading to the arrest of the drainage process. 

PMID- 26218201
TI  - Heme oxygenase-1 plays a crucial role in chemoresistance in acute myeloid
      leukemia.
AB  - OBJECTIVES: The heme oxygenase-1 (HO-1) gene may contribute to the development of
      acquired chemoresistance in solid tumor cells, but its function in acute myeloid
      leukemia (AML) remains unclear. Therefore, we investigated whether the
      expressions of HO-1 mRNA and protein were associated with AML chemoresistance.
      METHODS: Bone marrow or peripheral blood was obtained from newly diagnosed (n =
      26), relapsed (n = 10), and completely remitted (n = 18) patients with AML (M3
      exclusion) and healthy donors (n = 10). Small interfering RNA was used to stably
      silence HO-1 gene expression in AML cell lines. The expressions of HO-1, hypoxia
      inducible factor-1alpha (HIF-1alpha), glucose transporter-1 (GLUT1) mRNA and
      proteins were measured by quantitative real-time PCR and Western blot. Cell
      viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. Apoptosis induction was analyzed by flow cytometry. RESULTS:
      The drug-resistant AML cell line HL-60R was significantly less sensitive to
      cytarabine and daunorubicin than HL-60 cells. HO-1 mRNA and proteins were highly
      expressed in HL-60R cells. However, down-regulating HO-1 significantly enhanced
      the sensitivity of HL-60R to chemotherapy, and the expressions of HIF-1alpha and
      GLUT1 mRNA and proteins decreased. Meanwhile, the expressions of caspase-3 and
      caspase-8 proteins increased, while that of bcl-2 decreased. Overexpressions of
      HO-1, HIF-1alpha, and GLUT1 were associated with poor response of AML to
      chemotherapy. Conclusions Overexpressions of HO-1, HIF-1alpha, and GLUT1 might be
      involved in the chemoresistance of AML. HO-1 is a potential target to overcome
      the drug resistance of AML.

PMID- 26218202
TI  - Inherited bone marrow failure syndromes.

PMID- 26218203
TI  - Double Parricide: An In-Depth Look at Two Victim Homicides Involving Parents as
      Victims.
AB  - The majority of studies examining the killing of parents and step-parents by
      biological and stepchildren involve a single victim and single offender. Little
      is known when parricide incidents involve multiple victims or multiple offenders.
      Using the National Incident-Based Reporting System (NIBRS), this study examined
      double parricide incidents involving single or multiple offenders over the 20
      year period 1991-2010 with the aim of investigating juvenile and adult
      involvement. Forty-five incidents of double parricide were identified and
      verified; in 35 of these cases, the offenders acted alone. Frequencies reported
      include offender, victim, and incident characteristics. The results indicated
      that the typical double parricide offender who acted alone was a White male
      approximately 30 years of age. When multiple offenders were involved, the
      offenders tended to be younger and were more likely to include a female
      accomplice. Newspapers were utilized to augment available case information. Study
      limitations, implications, and directions for future research are also discussed.

PMID- 26218204
TI  - An update on the clinical pharmacology of the dipeptidyl peptidase 4 inhibitor
      alogliptin used for the treatment of type 2 diabetes mellitus.
AB  - Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor that is a class of
      relatively new oral hypoglycaemic drugs used in patients with type 2 diabetes
      (T2DM), can be used as monotherapy or in combination with other anti-diabetic
      agents, including metformin, pioglitazone, sulfonylureas and insulin with a
      considerable therapeutic effect. Alogliptin exhibits favorable pharmacokinetic
      and pharmacodynamic profiles in humans. Alogliptin is mainly metabolized by
      cytochrome P450 (CYP2D6) and CYP3A4. Dose reduction is recommended for patients
      with moderate or worse renal impairment. Side effects of alogliptin include
      nasopharyngitis, upper-respiratory tract infections and headache. Hypoglycaemia
      is seen in about 1.5% of the T2DM patients. Rare but severe adverse reactions
      such as acute pancreatitis, serious hypersensitivity including anaphylaxis,
      angioedema and severe cutaneous reactions such as Stevens-Johnson syndrome have
      been reported from post-marketing monitoring. Pharmacokinetic interactions have
      not been observed between alogliptin and other drugs including glyburide,
      metformin, pioglitazone, insulin and warfarin. The present review aimed to update
      the clinical information on pharmacodynamics, pharmacokinetics, adverse effects
      and drug interactions, and to discuss the future directions of alogliptin. 

PMID- 26218205
TI  - Relaxometry and Dephasing Imaging of Superparamagnetic Magnetite Nanoparticles
      Using a Single Qubit.
AB  - To study the magnetic dynamics of superparamagnetic nanoparticles, we use
      scanning probe relaxometry and dephasing of the nitrogen vacancy (NV) center in
      diamond, characterizing the spin noise of a single 10 nm magnetite particle.
      Additionally, we show the anisotropy of the NV sensitivity's dependence on the
      applied decoherence measurement method. By comparing the change in relaxation
      (T1) and dephasing (T2) time in the NV center when scanning a nanoparticle over
      it, we are able to extract the nanoparticle's diameter and distance from the NV
      center using an Ornstein-Uhlenbeck model for the nanoparticle's fluctuations.
      This scanning probe technique can be used in the future to characterize different
      spin label substitutes for both medical applications and basic magnetic
      nanoparticle behavior. 

PMID- 26218214
TI  - Induction and characterization of a replication competent cervid endogenous
      gammaretrovirus (CrERV) from mule deer cells.
AB  - Endogenous retroviruses (ERVs) were acquired during evolution of their host
      organisms after infection and mendelian inheritance in the germline by their
      exogenous counterparts. The ERVs can spread in the host genome and in some cases
      they affect the host phenotype. The cervid endogenous gammaretrovirus (CrERV) is
      one of only a few well-defined examples of evolutionarily recent invasion of
      mammalian genome by retroviruses. Thousands of insertionally polymorphic CrERV
      integration sites have been detected in wild ranging mule deer (Odocoileus
      hemionus) host populations. Here, we describe for the first time induction of
      replication competent CrERV by cocultivation of deer and human cells. We
      characterize the physical properties and tropism of the induced virus. The
      genomic sequence of the induced virus is phylogenetically related to the
      evolutionarily young endogenous CrERVs described so far. We also describe the
      level of replication block of CrERV on deer cells and its capacity to establish
      superinfection interference. 

PMID- 26218215
TI  - Mechanistic study of intertypic nucleoprotein complex formation and its
      inhibitory effect toward influenza A virus.
AB  - Co-infection of influenza A and B viruses (IAV and IBV) results in marked
      decreases in IAV replication. Multiple mechanisms have been proposed for this
      phenomenon. Recently, we reported that IBV nucleoprotein (BNP) alone can suppress
      IAV replication and proposed an inhibition model in which BNP binds IAV
      nucleoprotein (ANP) and disrupts IAV polymerase complexes. Here, using
      mutagenesis and co-immunoprecipitation, we determined the protein motifs
      mediating the intertypic ANP-BNP complex and showed that it specifically
      interferes with ANP's interaction with the PB2 subunit of the IAV polymerase but
      not with the other subunit PB1. We further demonstrated that BNP only suppresses
      growth of IAVs but not other RNA viruses. However, different IAV strains display
      varied sensitivity toward the BNP's inhibitory effect. Together, our data provide
      mechanistic insights into intertypic nucleoprotein complex formation and
      highlight the role of BNP as a potential broad-spectrum anti-IAV agent. 

PMID- 26218221
TI  - Colokinetic effect of noradrenaline in the spinal defecation center: implication
      for motility disorders.
AB  - Chronic abdominal pain in irritable bowel syndrome (IBS) usually appears in
      combination with disturbed bowel habits, but the etiological relationship between
      these symptoms remains unclear. Noradrenaline is a major neurotransmitter
      controlling pain sensation in the spinal cord. To test the hypothesis that the
      descending noradrenergic pathway from the brain stem moderates gut motility, we
      examined effects of intrathecal application of noradrenaline to the spinal
      defecation center on colorectal motility. Colorectal intraluminal pressure and
      expelled volume were recorded in vivo in anesthetized rats. Intrathecal
      application of noradrenaline into the L6-S1 spinal cord, where the lumbosacral
      defecation center is located, caused propulsive contractions of the colorectum.
      Inactivation of spinal neurons by tetrodotoxin blocked the effect of
      noradrenaline. Pharmacological experiments showed that the effect of
      noradrenaline is mediated primarily by alpha-1 adrenoceptors. The enhancement of
      colorectal motility by intrathecal noradrenaline was abolished by severing of the
      pelvic nerves. Our results demonstrate that noradrenaline acting on sacral
      parasympathetic preganglionic neurons through alpha-1 adrenoceptors causes
      propulsive motility of the colorectum in rats. Considering that visceral pain
      activates the descending inhibitory pathways including noradrenergic neurons, our
      results provide a rational explanation of the concurrent appearance of chronic
      abdominal pain and colonic motility disorders in IBS patients. 

PMID- 26218222
TI  - EIN3 and ORE1 Accelerate Degreening during Ethylene-Mediated Leaf Senescence by
      Directly Activating Chlorophyll Catabolic Genes in Arabidopsis.
AB  - Degreening, caused by chlorophyll degradation, is the most obvious symptom of
      senescing leaves. Chlorophyll degradation can be triggered by endogenous and
      environmental cues, and ethylene is one of the major inducers. ETHYLENE
      INSENSITIVE3 (EIN3) is a key transcription factor in the ethylene signaling
      pathway. It was previously reported that EIN3, miR164, and a NAC (NAM, ATAF, and
      CUC) transcription factor ORE1/NAC2 constitute a regulatory network mediating
      leaf senescence. However, how this network regulates chlorophyll degradation at
      molecular level is not yet elucidated. Here we report a feed-forward regulation
      of chlorophyll degradation that involves EIN3, ORE1, and chlorophyll catabolic
      genes (CCGs). Gene expression analysis showed that the induction of three major
      CCGs, NYE1, NYC1 and PAO, by ethylene was largely repressed in ein3 eil1 double
      mutant. Dual-luciferase assay revealed that EIN3 significantly enhanced the
      promoter activity of NYE1, NYC1 and PAO in Arabidopsis protoplasts. Furthermore,
      Electrophoretic mobility shift assay (EMSA) indicated that EIN3 could directly
      bind to NYE1, NYC1 and PAO promoters. These results reveal that EIN3 functions as
      a positive regulator of CCG expression during ethylene-mediated chlorophyll
      degradation. Interestingly, ORE1, a senescence regulator which is a downstream
      target of EIN3, could also activate the expression of NYE1, NYC1 and PAO by
      directly binding to their promoters in EMSA and chromatin immunoprecipitation
      (ChIP) assays. In addition, EIN3 and ORE1 promoted NYE1 and NYC1 transcriptions
      in an additive manner. These results suggest that ORE1 is also involved in the
      direct regulation of CCG transcription. Moreover, ORE1 activated the expression
      of ACS2, a major ethylene biosynthesis gene, and subsequently promoted ethylene
      production. Collectively, our work reveals that EIN3, ORE1 and CCGs constitute a
      coherent feed-forward loop involving in the robust regulation of ethylene
      mediated chlorophyll degradation during leaf senescence in Arabidopsis. 

PMID- 26218223
TI  - First quantitative high-throughput screen in zebrafish identifies novel pathways
      for increasing pancreatic beta-cell mass.
AB  - Whole-organism chemical screening can circumvent bottlenecks that impede drug
      discovery. However, in vivo screens have not attained throughput capacities
      possible with in vitro assays. We therefore developed a method enabling in vivo
      high-throughput screening (HTS) in zebrafish, termed automated reporter
      quantification in vivo (ARQiv). In this study, ARQiv was combined with robotics
      to fully actualize whole-organism HTS (ARQiv-HTS). In a primary screen, this
      platform quantified cell-specific fluorescent reporters in >500,000 transgenic
      zebrafish larvae to identify FDA-approved (Federal Drug Administration) drugs
      that increased the number of insulin-producing beta cells in the pancreas. 24
      drugs were confirmed as inducers of endocrine differentiation and/or stimulators
      of beta-cell proliferation. Further, we discovered novel roles for NF-kappaB
      signaling in regulating endocrine differentiation and for serotonergic signaling
      in selectively stimulating beta-cell proliferation. These studies demonstrate the
      power of ARQiv-HTS for drug discovery and provide unique insights into signaling
      pathways controlling beta-cell mass, potential therapeutic targets for treating
      diabetes. 

PMID- 26218224
TI  - Logics and properties of a genetic regulatory program that drives embryonic
      muscle development in an echinoderm.
AB  - Evolutionary origin of muscle is a central question when discussing mesoderm
      evolution. Developmental mechanisms underlying somatic muscle development have
      mostly been studied in vertebrates and fly where multiple signals and hierarchic
      genetic regulatory cascades selectively specify myoblasts from a pool of naive
      mesodermal progenitors. However, due to the increased organismic complexity and
      distant phylogenetic position of the two systems, a general mechanistic
      understanding of myogenesis is still lacking. In this study, we propose a gene
      regulatory network (GRN) model that promotes myogenesis in the sea urchin embryo,
      an early branching deuterostome. A fibroblast growth factor signaling and four
      Forkhead transcription factors consist the central part of our model and appear
      to orchestrate the myogenic process. The topological properties of the network
      reveal dense gene interwiring and a multilevel transcriptional regulation of
      conserved and novel myogenic genes. Finally, the comparison of the myogenic
      network architecture among different animal groups highlights the evolutionary
      plasticity of developmental GRNs. 

PMID- 26218225
TI  - The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen
      telomeres in S. cerevisiae.
AB  - In Saccharomyces cerevisiae and in humans, the telomerase RNA subunit is bound by
      Ku, a ring-shaped protein heterodimer best known for its function in DNA repair.
      Ku binding to yeast telomerase RNA promotes telomere lengthening and telomerase
      recruitment to telomeres, but how this is achieved remains unknown. Using
      telomere-length analysis and chromatin immunoprecipitation, we show that Sir4 - a
      previously identified Ku-binding protein that is a component of telomeric silent
      chromatin - is required for Ku-mediated telomere lengthening and telomerase
      recruitment. We also find that specifically tethering Sir4 directly to Ku-binding
      defective telomerase RNA restores otherwise-shortened telomeres to wild-type
      length. These findings suggest that Sir4 is the telomere-bound target of Ku
      mediated telomerase recruitment and provide one mechanism for how the Sir4
      competing Rif1 and Rif2 proteins negatively regulate telomere length in yeast.

PMID- 26218226
TI  - The complete chloroplast genome sequence of Ledebouriella seseloides (Hoffm.) H.
      Wolff.
AB  - Ledebouriella seseloides (Hoffm.) H.Wolff is a traditional medicinal herb
      belonging to Apiaceae family, whose dried roots and rhizomes have been used as
      traditional medicine in East Asian countries. The complete chloroplast genome of
      L. seseloides was obtained by de novo assembly using the small amount of whole
      genome sequencing data. The chloroplast genome of L. seseloides was 147 880 bp in
      length, which consisted of large single copy region (93 222 bp), small single
      copy region (17 324 bp), and a pair of inverted repeat regions (18 667 bp). The
      overall GC contents of the chloroplast genome were 37.5%. A total of 113 genes
      were annotated, which included 79 protein-coding genes, 30 tRNA genes, and four
      rRNA genes. Phylogenetic analysis with the reported chloroplast genomes revealed
      that L. seseloides is most closely related to Petroselinum crispum (parsley), an
      herb widely used in cooking.

PMID- 26218227
TI  - Ring Contraction of 3-Hydroxy-3-(trifluoromethyl)piperidines: Synthesis of 2
      Substituted 2-(Trifluoromethyl)pyrrolidines.
AB  - A ring contraction of 3-hydroxy-3-(trifluoromethyl)piperidines was achieved via
      an aziridinium intermediate. This contraction facilitates the synthesis of a
      series of 2-substituted 2-(trifluoromethyl)pyrrolidines incorporating a
      quaternary center at the C2 position. 

PMID- 26218229
TI  - Measuring Effects of Metaphor in a Dynamic Opinion Landscape.
AB  - Metaphors pervade discussions of critical issues, making up as much as 10-20% of
      natural discourse. Recent work has suggested that these conventional and
      systematic metaphors influence the way people reason about the issues they
      describe. For instance, previous work has found that people were more likely to
      want to fight back against a crime beast by increasing the police force but more
      likely to want to diagnose and treat a crime virus through social reform. Here,
      we report the results of three norming tasks and two experiments that reveal a
      shift in the overall landscape of opinion on the topic of crime. Importantly, we
      find that the metaphors continue to have an influence on people's reasoning about
      crime. Our results and analyses highlight the importance of up-to-date opinion
      norms and carefully controlled materials in metaphor research. 

PMID- 26218228
TI  - Direct versus Indirect Treatment for Preschool Children who Stutter: The RESTART
      Randomized Trial.
AB  - OBJECTIVE: Stuttering is a common childhood disorder. There is limited high
      quality evidence regarding options for best treatment. The aim of the study was
      to compare the effectiveness of direct treatment with indirect treatment in
      preschool children who stutter. METHODS: In this multicenter randomized
      controlled trial with an 18 month follow-up, preschool children who stutter who
      were referred for treatment were randomized to direct treatment (Lidcombe
      Program; n = 99) or indirect treatment (RESTART-DCM treatment; n = 100). Main
      inclusion criteria were age 3-6 years, >=3% syllables stuttered (%SS), and time
      since onset >=6 months. The primary outcome was the percentage of non-stuttering
      children at 18 months. Secondary outcomes included stuttering frequency (%SS),
      stuttering severity ratings by the parents and therapist, severity rating by the
      child, health-related quality of life, emotional and behavioral problems, and
      speech attitude. RESULTS: Percentage of non-stuttering children for direct
      treatment was 76.5% (65/85) versus 71.4% (65/91) for indirect treatment (Odds
      Ratio (OR), 0.6; 95% CI, 0.1-2.4, p = .42). At 3 months, children treated by
      direct treatment showed a greater decline in %SS (significant interaction time x
      therapy: beta = -1.89; t(282.82) = -2.807, p = .005). At 18 months, stuttering
      frequency was 1.2% (SD 2.1) for direct treatment and 1.5% (SD 2.1) for indirect
      treatment. Direct treatment had slightly better scores on most other secondary
      outcome measures, but no differences between treatment approaches were
      significant. CONCLUSIONS: Direct treatment decreased stuttering more quickly
      during the first three months of treatment. At 18 months, however, clinical
      outcomes for direct and indirect treatment were comparable. These results imply
      that at 18 months post treatment onset, both treatments are roughly equal in
      treating developmental stuttering in ways that surpass expectations of natural
      recovery. Follow-up data are needed to confirm these findings in the longer term.
      TRIAL REGISTRATION: isrctn.org ISRCTN24362190.

PMID- 26218230
TI  - Efficient Preparation of Super Antifouling PVDF Ultrafiltration Membrane with One
      Step Fabricated Zwitterionic Surface.
AB  - On the basis of the excellent fouling resistance of zwitterionic materials, the
      super antifouling polyvinylidene fluoride (PVDF) membrane was efficiently
      prepared though one-step sulfonation of PVDF and polyaniline blend membrane in
      situ. The self-doped sulfonated polyaniline (SPANI) was generated as a novel
      zwitterionic polymer to improve the antifouling property of PVDF ultrafiltration
      membrane used in sewage treatment. Surface attenuated total reflection Fourier
      transform infrared spectroscopy, X-ray photoelectron spectroscopy, surface zeta
      potential, and water contact angle demonstrated the successful fabrication of
      zwitterionic interface by convenient sulfonation modification. The static
      adsorption fouling test showed the quantified adsorption mass of bovine serum
      albumin (BSA) pollutant on the PVDF/SPANI membrane surface decreases to 3(+/-2)
      MUg/cm(2), and the water flux recovery ratio (FRR) values were no less than 95%
      for the three model pollutants of BSA, sodium alginate (SA), and humic acid (HA),
      which were corresponding hydrophobic, hydrophilic, and natural pollutants in
      sewage, respectively. This Research Article demonstrated the antifouling
      advantages of zwitterionic SPANI and aimed to provide a simple method for the
      large scale preparation of zwitterionic antifouling ultrafiltration membranes. 

PMID- 26218231
TI  - Effects of 6 Weeks Resistance Training Combined With Plyometric and Speed
      Exercises on Physical Performance of Pre-Peak-Height-Velocity Soccer Players.
AB  - PURPOSE: To analyze the effects of low-load, high-velocity resistance training
      (RT) combined with plyometrics on physical performance in pre-peak-height
      velocity (PHV) soccer players. METHODS: Thirty young soccer players from the same
      academy were randomly assigned to either a strength training (STG, n = 15) or a
      control group (CG, n = 15). Strength training consisted of full squat exercise
      with low load (45-58% 1RM) and low volume (4-8 repetitions/set) combined with
      jumps and sprints twice a week over 6 wk of preseason. The effect of the training
      protocol was assessed using sprint performance over 10 and 20 m, countermovement
      jump, estimated 1-repetition maximum, and average velocity attained against all
      loads common to pre- and posttests in full squat. RESULTS: STG showed significant
      improvements (P = .004-.001) and moderate to very large standardized effects (ES
      = 0.71-2.10) in all variables measured, whereas no significant gains were found
      in CG (ES = -0.29 to 0.06). Moreover, significant test * group interactions (P <
      .003-.001) and greater between-groups ESs (0.90-1.97) were found for all
      variables in favor of STG compared with CG. CONCLUSION: Only 6 wk of preseason
      low-volume and low-load RT combined with plyometrics can lead to relevant
      improvements in strength, jump, and sprint performance. Thus, the combination of
      field soccer training and lightweight strength training could be used for a
      greater development of the tasks critical to soccer performance in pre-PHV soccer
      players.

PMID- 26218232
TI  - Rates and Routes of Electron Transfer of [NiFe]-Hydrogenase in an Enzymatic Fuel
      Cell.
AB  - Hydrogenase enzymes are being used in enzymatic fuel cells immobilized on a
      graphite or carbon electrode surface, for example. The enzyme is used for the
      anodic oxidation of molecular hydrogen (H2) to produce protons and electrons. The
      association and orientation of the enzyme at the anode electrode for a direct
      electron transfer is not completely resolved. The distal FeS-cluster in [NiFe]
      hydrogenases contains a histidine residue which is known to play a critical role
      in the intermolecular electron transfer between the enzyme and the electrode
      surface. The [NiFe]-hydrogenase graphite electrode association was investigated
      using Brownian Dynamics simulations. Residues that were shown to be in proximity
      to the electrode surface were identified (His184, Ser196, Glu461, Glu464), and
      electron transfer routes connecting the distal FeS-cluster with the surface
      residues were investigated. Several possible pathways for electron transfer
      between the distal FeS-cluster and the terminal amino acid residues were probed
      in terms of their rates of electron transfer using DFT methods. The
      reorganization energies lambda of the distal iron-sulfur cluster and coronene as
      a molecular model for graphite were calculated. The reorganization energy of the
      distal (His)(Cys)3 cluster was found to be not very different from that of a
      standard cubane clusters with a (Cys)4 coordination. Electronic coupling matrix
      elements and rates of electron transfer for the different pathways were
      calculated according to the Marcus equation. The rates for glutamate-mediated
      electrode binding were found to be incompatible with experimental data. A direct
      electron transfer from the histidine ligand of the distal FeS-cluster to the
      electrode yielded rates of electron transfer in excellent agreement with
      experiment. A second pathway, however, from the distal FeS-cluster to the Ser196
      residue was found to be equally efficient and feasible. 

PMID- 26218233
TI  - Factor Structure of the Positive and Negative Syndrome Scale (PANSS) Differs by
      Sex.
AB  - Although the Positive and Negative Syndrome Scale (PANSS) is widely used in
      clinical research, factor analytic studies of the scale have been inconsistent
      and questions remain about the underlying factor structure of schizophrenia
      symptoms. The purpose of this study was to examine whether the factor structure
      of the PANSS differs in men and women with schizophrenia. Principal components
      analysis (PCA) with equamax rotation was used to examine the factor structure of
      the PANSS separately in 124 males and 74 females with schizophrenia-related
      psychoses. In males, a four-factor structure was identified: 1) Negative, 2)
      Cognitive, 3) Positive, and 4) Hostility. In females, a four-factor structure
      also emerged: 1) Negative, 2) Cognitive, 3) Positive, and 4) Depression. The most
      notable difference between the male and female PCAs was the presence of a
      depression factor in the females and a hostility factor in males. These results
      support sex differences in the factor structure of schizophrenia symptoms, which
      has important implications for clinical research.

PMID- 26218234
TI  - Sex, Age, Symptoms and Illness Duration and Their Relation with Gyrification
      Index in Schizophrenia.
AB  - INTRODUCTION: The Gyrification Index (GI) represents the degree of cortical
      folding and is of special interest in schizophrenia, since alterations in
      cortical folding indirectly reflect white matter development and axonal
      connectivity underneath. To the best of our knowledge, very few studies have
      investigated the effect of sex on GI in schizophrenia. Differences in the GI
      between patients with schizophrenia and healthy controls and the relation between
      sex, age symptoms and duration of illness with GI were investigated. METHODS: T1
      images were acquired from schizophrenia patients (24 males [SZ-M] and 24 females
      [SZ-F]) and healthy volunteers (24 males [NC-M] and 24 females [NC-F]) matched
      for age, sex and handedness. GI analyses were performed using the fully automated
      CIVET pipeline. RESULTS: Significantly lower GI was found in patients relative to
      controls bilaterally in frontal, temporal, and parietal cortex. Sex differences
      were found: negative correlation was found between the duration of illness and
      the right parietal GI and right occipital GI in SZ-M, while SZ-F was found in the
      left frontal and bilateral temporal GI. Patients, regardless of sex, showed
      positive correlations between negative symptoms and GI in the right occipital. NC
      F had greater GI values than SZ-F and both male groups. CONCLUSIONS: Since GI
      reflects, in part, alterations in cerebral development and connectivity, the
      decrease in GI observed in patients is in agreement with the neurodevelopmental
      model of disconnectivity in schizophrenia; in addition, we emphasize the
      importance of sex differences in schizophrenia.

PMID- 26218235
TI  - Blood Draw Barriers for Treatment with Clozapine and Development of a Point-of
      Care Monitoring Device.
AB  - BACKGROUND: While clozapine (CLZ) is the most effective antipsychotic drug for
      schizophrenia treatment, it remains underused. In order to understand the
      barriers of frequent blood draws for white blood cell counts (WBCs) and clozapine
      levels, we developed a psychiatrist survey and began an integrative approach of
      designing a point-of-care device that could eventually have real-time monitoring
      with immediate results. METHODS: We ascertained barriers related to CLZ
      management and the acceptance of possible solutions by sending an anonymous
      survey to physicians in psychiatric practice (n=860). In parallel, we tested CLZ
      sensing using a prototype point-of-care monitoring device. RESULTS: 255 responses
      were included in the survey results. The two barriers receiving mean scores with
      the highest agreement as being a significant barrier were patient nonadherence to
      blood work and blood work's burden on the patient (out of 28). Among nine
      solutions, the ability to obtain lab results in the physician's office or
      pharmacy was top ranked (mean+/-sd Likert scale [4.0+/-1.0]). Physicians
      responded that a point-of-care device to measure blood levels and WBCs would
      improve care and increase CLZ use. Residents ranked point-of-care devices higher
      than older physicians (4.07+/-0.87 vs. 3.47+/-1.08, p<0.0001). Also, the
      prototype device was able to detect CLZ reliably in 1.6, 8.2, and 16.3 MUg/mL
      buffered solutions. DISCUSSION: Survey results demonstrate physicians' desire for
      point-of-care monitoring technology, particularly among younger prescribers.
      Prototype sensor results identify that CLZ can be detected and integrated for
      future device development. Future development will also include integration of
      WBCs for a complete detection device.

PMID- 26218236
TI  - Add-On Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative
      and Anxiety Symptoms of Schizophrenia: An 8-Week, Randomized, Double-Blind,
      Placebo-Controlled Trial.
AB  - AIMS: Pregnenolone (PREG) and L-theanine (LT) have shown ameliorative effects on
      various schizophrenia symptoms. This is the first study to evaluate the efficacy
      and safety of augmentation of antipsychotic treatment among patients with chronic
      schizophrenia or schizoaffective disorder with PREG-LT. METHODS: Double-blind,
      placebo-controlled trial of PREG-LT or placebo augmentation was conducted for
      eight weeks with 40 chronic DSM-IV schizophrenia and schizoaffective disorder
      patients with suboptimal response to antipsychotics. Oral PREG (50 mg/day) with
      LT (400 mg/day) or placebo were added to a stable regimen of antipsychotic
      medication from March 2011 to October 2013. The participants were rated using the
      Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Scale for
      Anxiety (HAM-A), and the Positive and Negative Syndrome Scale (PANSS) scales bi
      weekly. The decrease of SANS and HAM-A scores were the co-primary outcomes.
      Secondary outcomes included assessments of general functioning and side effects.
      RESULTS: Negative symptoms such as blunted affect, alogia, and anhedonia (SANS)
      were found to be significantly improved with moderate effect sizes among patients
      who received PREG-LT, in comparison with the placebo group. Add-on PREG-LT also
      significantly associated with a reduction of anxiety scores such as anxious mood,
      tension, and cardiovascular symptoms (HAM-A), and elevation of general
      functioning (GAF). Positive symptoms, antipsychotic agents, concomitant drugs,
      and illness duration did not associate significantly with effect of PREG-LT
      augmentation. PREG-LT was well-tolerated. CONCLUSIONS: Pregnenolone with L
      theanine augmentation may offer a new therapeutic strategy for treatment of
      negative and anxiety symptoms in schizophrenia and schizoaffective disorder.
      Further studies are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT01831986.

PMID- 26218237
TI  - Attitudes Toward Medications and the Relationship to Outcomes in Patients with
      Schizophrenia.
AB  - The determinants of attitudes toward medication (ATM) are not well elucidated. In
      particular, literature remains equivocal regarding the influence of cognition,
      adverse events, and psychiatric symptomatology. This study evaluated
      relationships between those outcomes in schizophrenia and ATM. This is a
      retrospective analysis of data collected during the Texas Medication Algorithm
      Project (TMAP, n=307 with schizophrenia-related diagnoses), in outpatient clinics
      at baseline and every 3 months for >=1 year (for cognition: 3rd and 9th month
      only). The Drug Attitude Inventory (DAI-30) measured ATM, and independent
      variables were: cognition (Trail Making Test [TMT], Verbal Fluency Test, Hopkins
      Verbal Learning Test), adverse events (Systematic Assessment for Treatment
      Emergent Adverse Events, Barnes Akathisia Rating Scale), psychiatric
      symptomatology (Brief Psychiatric Rating Scale, Scale for Assessment of Negative
      Symptoms [SANS]), and medication adherence (Medication Compliance Scale).
      Analyses included binary logistic regression (cognition, psychiatric symptoms)
      and chi-square (adverse events, adherence) for baseline comparisons, and linear
      regression (cognition) or ANOVA (adverse events, adherence) for changes over
      time. Mean DAI-30 scores did not change over 12 months. Odds of positive ATM
      increased with higher TMT Part B scores (p=0.03) and lower SANS scores (p=0.02).
      Worsening of general psychopathology (p<0.001), positive symptoms (p<0.001), and
      negative symptoms (p=0.007) correlated with negative changes in DAI-30 scores.
      Relationships between cognition, negative symptoms, and ATM warrant further
      investigation. Studies evaluating therapies for cognitive deficits and negative
      symptoms should consider including ATM measures as endpoints. Patterns and
      inconsistencies in findings across studies raise questions about whether some
      factors thought to influence ATM have nonlinear relationships.

PMID- 26218238
TI  - Correlates of Suicide-Related Ideations and Attempts in Patients with Acute and
      Transient Psychotic Disorder.
AB  - INTRODUCTION: Acute and transient psychotic disorder (ATPD) is a brief, self
      limiting psychiatric disorder commonly seen in developing countries. This
      condition is associated with an elevated risk of suicide, but data on this
      association are lacking in developing countries. METHODOLOGY: Consecutive
      outpatients with a diagnosis ATPD as per ICD-10 criteria (n=29) were recruited
      over a period of six months (February-July 2014) and retrospectively assessed for
      suicide-related ideations and attempts and their correlates both during and in
      between episodes of their illness. RESULTS: A total of 16 patients (55.17%)
      experienced suicide-related ideations, which occurred during a psychotic episode
      in 14 patients. Six patients (20.69%) made suicide attempts. A later age of onset
      was significantly associated with suicidality (p=0.04), as was a family history
      of depression or related ("spectrum") conditions (p<0.01). A relationship with
      higher educational status, reported in an earlier study, was not replicated in
      our sample. CONCLUSIONS: Suicide-related ideation and suicide attempts are common
      in ATPD, and may be linked to a later onset and a genetic loading for depression
      related conditions.

PMID- 26218239
TI  - Prevalence and Characteristics of Hepatitis B Virus (HBV) Coinfection among HIV
      Positive Women in South Africa and Botswana.
AB  - There is progressive concern about the evolving burden of morbidity and mortality
      caused by coinfection with HIV-1 and hepatitis B virus (HBV) in sub-Saharan
      Africa, but the epidemiology and impact of this problem are not well defined. We
      therefore set out to assimilate more information about the nature of HBV/HIV
      coinfection in this region by undertaking a retrospective observational study of
      southern African adult women. We used samples from previously recruited HIV-1
      positive women attending antenatal clinics in three settings in South Africa and
      Botswana (n = 950) and added a small cohort of HIV-negative antenatal South
      African women for comparison (n = 72). We tested for HBsAg and followed up HBsAg
      positive samples by testing for HBeAg, HBV DNA, HBV genotype, presence of drug
      resistance associated mutations (RAMs) and HDV. We identified HBsAg in 72
      individuals (7% of the whole cohort), of whom 27% were HBeAg-positive, and the
      majority HBV genotypes A1 and A2. We did not detect any HDV coinfection. HBV
      prevalence was significantly different between geographically distinct cohorts,
      but did not differ according to HIV status. Among adults from South Africa,
      HBV/HIV coinfected patients had lower CD4+ T cell counts compared to those with
      HIV-monoinfection (p = 0.02), but this finding was not replicated in the cohort
      from Botswana. Overall, these data provide a snapshot of the coinfection problem
      at the heart of the HIV/HBV co-epidemic, and are important to inform public
      health policy, resource allocation, education, surveillance and clinical care. 

PMID- 26218240
TI  - Symptom profiles in children with advanced cancer: Patient, family caregiver, and
      oncologist ratings.
AB  - BACKGROUND: Systematic symptom assessment is not routinely performed in pediatric
      oncology. The objectives of the current study were to characterize the symptoms
      of pediatric oncology outpatients and evaluate agreement between patient and
      proxy reports and the association between children's ratings and oncologists'
      treatment recommendations. METHODS: Two versions of the pediatric Memorial
      Symptom Assessment Scale (pMSAS) were translated into Spanish. An age-appropriate
      and language-appropriate pMSAS was administered independently before visits to
      the oncologist to patients and family caregivers (caregivers) and after visits to
      consenting oncologists. Statistical analysis included Spearman correlation
      coefficients and weighted kappa values. RESULTS: English and Spanish results were
      similar and were combined. A total of 60 children and their caregivers completed
      the pMSAS. The children had a median age of 10 years (range, 7-18 years);
      approximately 62% were male and 33% were Spanish-speaking. Fourteen oncologists
      completed the pMSAS for 25 patients. Nine patients (15%) had no symptoms and 38
      patients (63%) reported >=2 symptoms. The most common symptoms were fatigue (12
      patients; 40%) and itch (9 patients; 30%) for the younger children and pain (15
      patients; 50%) and lack of energy (13 patients; 45%) among the older children.
      Total and subscale score agreement varied by proxy type and subscale, ranging
      from fair to good for most comparisons. Agreement for individual symptoms between
      the patient and proxy ranged from a kappa of -0.30 (95% confidence interval, 
      0.43 to -0.01) to 0.91 (95% confidence interval, 0.75 to 1.00). Three of 51
      symptomatic patients (6%) had treatment recommendations documented in the
      electronic health record. CONCLUSIONS: Symptoms are common and cross several
      functional domains. Proxy and child reports are often not congruent, possibly
      explaining apparent undertreatment among this group of patients.

PMID- 26218241
TI  - Microorganisms linked to inflammatory bowel disease-associated dysbiosis
      differentially impact host physiology in gnotobiotic mice.
AB  - Studying host-microbiota interactions are fundamental to understanding the
      mechanisms involved in intestinal homeostasis and inflammation. In this work, we
      analyzed these interactions in mice that were mono-associated with six
      microorganisms that are representative of inflammatory bowel disease (IBD)
      associated dysbiosis: the bacteria Bacteroides thetaiotaomicron, adhesive
      invasive Escherichia coli (AIEC), Ruminococcus gnavus and Roseburia intestinalis;
      a yeast used as a probiotic drug, Saccharomyces boulardii CNCM I-745; and another
      yeast, Candida albicans. Extensive ex vivo analyses including colon
      transcriptomics, histology, immune response, bile acid metabolism and short-chain
      fatty acid production were studied. We showed that B. thetaiotaomicron had the
      highest impact on the immune system because it was almost able to recapitulate
      the effects of the entire conventional microbiota and notably induced Treg
      pathways. Furthermore, these analyses uncovered the effects of E. coli AIEC LF82
      on indoleamine 2,3-dioxygenase expression and of S. boulardii CNCM I-745 on
      angiogenesis. These results were confirmed in vitro in human cell lines. Finally,
      our results suggested that R. gnavus has major effects on metabolism, and notably
      on tryptophan metabolism. This work therefore reveals that microorganisms with a
      potential role in intestinal homeostasis and inflammation have specific impacts
      on the host, and it suggests several tracks to follow to understand intestinal
      homeostasis and IBD pathogenesis better, providing new insights to identify novel
      therapeutic targets. 

PMID- 26218242
TI  - Indirect positive effects of a sigma factor RpoN deletion on the lactate-based
      polymer production in Escherichia coli.
AB  - The production of bacterial polyesters, polyhydroxyalkanoates (PHAs), has been
      improved by several rational approaches such as overexpression and/or engineering
      of the enzymes directly related to PHA biosynthetic pathways. In this study, a
      new approach at transcription level has been applied to a new category of the
      copolymer of lactate (LA) and 3-hydroxybutyrate (3HB), P(LA-co-3HB). When the 4
      disrupting mutants of sigma factors in Escherichia coli, rpoN, rpoS, fliA, fecI,
      were used as platforms for production of P(LA-co-3HB), increases in the
      production level and LA fraction of the copolymer were observed for the mutant
      strain with rpoN disruption. These positive impacts on the polymer production
      were caused in an "indirect manner" via changes in the multiple genes governed by
      RpoN. A genome-wide engineering by sigma factors would be a versatile approach
      for the production of value-added products of interest and available for
      combination with the other beneficial tools. 

PMID- 26218243
TI  - Cat Ownership Perception and Caretaking Explored in an Internet Survey of People
      Associated with Cats.
AB  - People who feed cats that they do not perceive they own (sometimes called semi
      owners) are thought to make a considerable contribution to unwanted cat numbers
      because the cats they support are generally not sterilized. Understanding
      people's perception of cat ownership and the psychology underlying cat semi
      ownership could inform approaches to mitigate the negative effects of cat semi
      ownership. The primary aims of this study were to investigate cat ownership
      perception and to examine its association with human-cat interactions and
      caretaking behaviours. A secondary aim was to evaluate a definition of cat semi
      ownership (including an association time of >=1 month and frequent feeding),
      revised from a previous definition proposed in the literature to distinguish cat
      semi-ownership from casual interactions with unowned cats. Cat owners and semi
      owners displayed similar types of interactions and caretaking behaviours.
      Nevertheless, caretaking behaviours were more commonly displayed towards owned
      cats than semi-owned cats, and semi-owned cats were more likely to have produced
      kittens (p<0.01). All interactions and caretaking behaviours were more likely to
      be displayed towards cats in semi-ownership relationships compared to casual
      interaction relationships. Determinants of cat ownership perception were
      identified (p<0.05) and included association time, attachment, perceived cat
      friendliness and health, and feelings about unowned cats, including the
      acceptability of feeding unowned cats. Encouraging semi-owners to have the cats
      they care for sterilized may assist in reducing the number of unwanted kittens
      and could be a valuable alternative to trying to prevent semi-ownership entirely.
      Highly accessible semi-owner "gatekeepers" could help to deliver education
      messages and facilitate the provision of cat sterilization services to semi
      owners. This research enabled semi-ownership to be distinguished from casual
      interaction relationships and can assist welfare and government agencies to
      identify cat semi-owners in order to develop strategies to address this source of
      unwanted cats. 

PMID- 26218244
TI  - Correction: A Fatty Acid Based Bayesian Approach for Inferring Diet in Aquatic
      Consumers.

PMID- 26218245
TI  - Shh Signaling through the Primary Cilium Modulates Rat Oligodendrocyte
      Differentiation.
AB  - Primary Cilia (PC) are a very likely place for signal integration where multiple
      signaling pathways converge. Two major signaling pathways clearly shown to signal
      through the PC, Sonic Hedgehog (Shh) and PDGF-Ralpha, are particularly important
      for the proliferation and differentiation of oligodendrocytes, suggesting that
      their interaction occurs in or around this organelle. We identified PC in rat
      oligodendrocyte precursor cells (OPCs) and found that, while easily detectable in
      early OPCs, PC are lost as these cells progress to terminal differentiation. We
      confirmed the interaction between these pathways, as cyclopamine inhibition of
      Hedgehog function impairs both PDGF-mediated OPC proliferation and Shh-dependent
      cell branching. However, we failed to detect PDGF-Ralpha localization into the
      PC. Remarkably, ciliobrevin-mediated disruption of PC and reduction of OPC
      process extension was counteracted by recombinant Shh treatment, while PDGF had
      no effect. Therefore, while PDGF-Ralpha-dependent OPC proliferation and survival
      most probably does not initiate at the PC, still the integrity of this organelle
      and cilium-centered pathway is necessary for OPC survival and differentiation. 

PMID- 26218246
TI  - Ion channel therapeutics for pain.
AB  - Pain is a complex disease which can progress into a debilitating condition. The
      effective treatment of pain remains a challenge as current therapies often lack
      the desired level of efficacy or tolerability. One therapeutic avenue, the
      modulation of ion channel signaling by small molecules, has shown the ability to
      treat pain. However, of the 215 ion channels that exist in the human genome, with
      85 ion channels having a strong literature link to pain, only a small number of
      these channels have been successfully drugged for pain. The focus of future
      research will be to fully explore the possibilities surrounding these unexplored
      ion channels. Toward this end, a greater understanding of ion channel modulation
      will be the greatest tool we have in developing the next generation of drugs for
      the treatment of pain. 

PMID- 26218247
TI  - Functionalised inherently conducting polymers as low biofouling materials.
AB  - Diatoms are a major component of microbial biofouling layers that develop on man
      made surfaces placed in aquatic environments, resulting in significant economic
      and environmental impacts. This paper describes surface functionalisation of the
      inherently conducting polymers (ICPs) polypyrrole (PPy) and polyaniline (PANI)
      with poly(ethylene glycol) (PEG) and their efficacy as fouling resistant
      materials. Their ability to resist interactions with the model protein bovine
      serum albumin (BSA) was tested using a quartz crystal microbalance with
      dissipation monitoring (QCM-D). The capacity of the ICP-PEG materials to prevent
      settlement and colonisation of the fouling diatom Amphora coffeaeformis (Cleve)
      was also assayed. Variations were demonstrated in the dopants used during ICP
      polymerisation, along with the PEG molecular weight, and the ICP-PEG reaction
      conditions, all playing a role in guiding the eventual fouling resistant
      properties of the materials. Optimised ICP-PEG materials resulted in a
      significant reduction in BSA adsorption, and > 98% reduction in diatom adhesion. 

PMID- 26218248
TI  - A novel self-care biomechanical treatment for obese patients with knee
      osteoarthritis.
AB  - AIM: To examine the effect of a novel biomechanical, home-based, gait training
      device on gait patterns of obese individuals with knee OA. METHODS: This was a
      retrospective analysis of 105 (32 males, 73 females) obese (body mass index > 30
      kg/m2 ) subjects with knee OA who completed a 12-month program using a
      biomechanical gait training device and performing specified exercises. They
      underwent a computerized gait test to characterize spatiotemporal parameters, and
      completed the Western Ontario and McMaster Osteoarthritis Index (WOMAC)
      questionnaire and Short Form-36 (SF-36) Health Survey. They were then fitted with
      biomechanical gait training devices and began a home-based exercise program. Gait
      patterns and clinical symptoms were assessed after 3 and 12 months of therapy.
      RESULTS: Each gait parameter improved significantly at 3 months and more so at 12
      months (P = 0.03 overall). Gait velocity increased by 11.8% and by 16.1%,
      respectively. Single limb support of the more symptomatic knee increased by 2.5%
      and by 3.6%, respectively. There was a significant reduction in pain, stiffness
      and functional limitation at 3 months (P < 0.001 for each) that further improved
      at 12 months. Pain decreased by 34.7% and by 45.7%, respectively. Functional
      limitation decreased by 35.0% and by 44.7%, respectively. Both the Physical and
      Mental Scales of the SF-36 increased significantly (P < 0.001) at 3 months and
      more so following 12 months. CONCLUSIONS: Obese subjects with knee OA who
      complied with a home-based exercise program using a biomechanical gait training
      device demonstrated a significant improvement in gait patterns and clinical
      symptoms after 3 months, followed by an additional improvement after 12 months.

PMID- 26218249
TI  - Age-Related Changes in Ocular Blood Velocity in Suspects with Glaucomatous Optic
      Disc Appearance. Comparison with Healthy Subjects and Glaucoma Patients.
AB  - PURPOSE: To evaluate retrobulbar blood flow characteristics of glaucoma suspects
      with glaucomatous optic disc appearance (GODA) in comparison to healthy control
      group (CG) and primary open angle glaucoma patients (POAG) and assess the effect
      of age. METHODS: 145 patients from a single glaucoma clinic were enrolled and
      classified into two diagnostic groups (GODA and POAG). Third group of subjects
      consisted of 67 age matched individuals (CG). Retrobulbar blood velocity
      measurement in central retinal artery was performed using color Doppler imaging
      (CDI). CDI images were processed in custom software leading a range of parameter
      estimates from a continuous waveform signal. The effect of age on the estimated
      parameters was evaluated with the stepwise forward regression and ANCOVA in which
      age was used as a continuous factor. One-way ANOVA was used to test for the
      differences in the CDI parameters between the three considered groups.
      Correlation between restive index (RI) and pulsatility index (PI) was assessed
      with a bilinear fitting guaranteeing no discontinuities in RI intercept estimate.
      Fisher test was used to assess the applicability of a bilinear PI/RI
      relationship, while the statistics of the RI intercept estimate were evaluated
      using the bootstrap. RESULTS: ANCOVA showed significant interaction between age
      and group (p<0.05) for five out of nine considered CDI parameters. The RI
      intercept for CG and GODA groups was 0.602+/-0.047, and 0.574+/-0.044
      respectively, while the RI intercept of 0.934+/-0.066 was found for the POAG.
      CONCLUSIONS: The observed similarity of CG and GODA group and dissimilarity
      between GODA and POAG groups in terms of PI/RI relationship is remarkable. Age
      may play some role in the different mechanisms occurring in blood velocity
      dynamics in GODA and POAG subjects but it is not a strongly determining factor.

PMID- 26218251
TI  - Fluorescent Microspheres as Point Sources: A Localization Study.
AB  - The localization of fluorescent microspheres is often employed for drift
      correction and image registration in single molecule microscopy, and is commonly
      carried out by fitting a point spread function to the image of the given
      microsphere. The mismatch between the point spread function and the image of the
      microsphere, however, calls into question the suitability of this localization
      approach. To investigate this issue, we subject both simulated and experimental
      microsphere image data to a maximum likelihood estimator that localizes a
      microsphere by fitting an Airy pattern to its image, and assess the suitability
      of the approach by evaluating the ability of the estimator to recover the true
      location of the microsphere with the best possible accuracy as determined based
      on the Cramer-Rao lower bound. Assessing against criteria based on the standard
      errors of the mean and the variance for an ideal estimator of the microsphere's
      location, we find that microspheres up to 100 nm in diameter can in general be
      localized using a fixed width Airy pattern, and that microspheres as large as 1
      MUm in diameter can in general be localized using a floated width Airy pattern. 

PMID- 26218250
TI  - Lipopolysaccharide Exposure Induces Maternal Hypozincemia, and Prenatal Zinc
      Treatment Prevents Autistic-Like Behaviors and Disturbances in the Striatal
      Dopaminergic and mTOR Systems of Offspring.
AB  - Autism is characterized by social deficits, repetitive behaviors, and cognitive
      inflexibility. The risk factors appear to include genetic and environmental
      conditions, such as prenatal infections and maternal dietary factors. Previous
      investigations by our group have demonstrated that prenatal exposure to
      lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria,
      induces autistic-like behaviors. To understand the causes of autistic-like
      behaviors, we evaluated maternal serum metal concentrations, which are involved
      in intrauterine development and infection/inflammation. We identified reduced
      maternal levels of zinc, magnesium, selenium and manganese after LPS exposure.
      Because LPS induced maternal hypozincemia, we treated dams with zinc in an
      attempt to prevent or ease the impairments in the offspring. We evaluated the
      social and cognitive autistic-like behaviors and brain tissues of the offspring
      to identify the central mechanism that triggers the development of autism.
      Prenatal LPS exposure impaired play behaviors and T-maze spontaneous
      alternations, i.e., it induced autistic-like behaviors. Prenatal LPS also
      decreased tyrosine hydroxylase levels and increased the levels of mammalian
      target of rapamycin (mTOR) in the striatum. Thus, striatal dopaminergic
      impairments may be related to autism. Moreover, excessive signaling through the
      mTOR pathway has been considered a biomarker of autism, corroborating our rat
      model of autism. Prenatal zinc treatment prevented these autistic-like behaviors
      and striatal dopaminergic and mTOR disturbances in the offspring induced by LPS
      exposure. The present findings revealed a possible relation between maternal
      hypozincemia during gestation and the onset of autism. Furthermore, prenatal zinc
      administration appears to have a beneficial effect on the prevention of autism. 

PMID- 26218252
TI  - Impact of a Telehealth and Care Management Program on All-Cause Mortality and
      Healthcare Utilization in Patients with Heart Failure.
AB  - BACKGROUND: Telehealth has the potential to improve chronic disease management
      and outcomes, but data regarding direct benefit of telehealth in patients with
      heart failure (HF) have been mixed. The objective of this study was to determine
      whether the Health Buddy Program (HBP) (Bosch Healthcare, Palo Alto, CA), a
      content-driven telehealth system coupled with care management, is associated with
      improved outcomes in Medicare beneficiaries with HF. MATERIALS AND METHODS: This
      was a retrospective cohort study of 623 Medicare beneficiaries with HF offered
      HBP enrollment compared with a propensity score-matched control group of Medicare
      beneficiaries with HF from the Medicare 5% sample. Associations between
      availability of the HBP and all-cause mortality, hospitalization, hospital days,
      and emergency department visits were evaluated. RESULTS: Beneficiaries offered
      enrollment in the HBP had 24.9% lower risk-adjusted all-cause mortality over 3
      years of follow-up (hazard ratio [HR] = 0.75; 95% confidence interval [CI], 0.63
      0.89; p = 0.001). Patients who used the HBP at least once (36.9%) had 57.2% lower
      mortality compared with matched controls (HR = 0.43; 95% CI, 0.31-0.60; p <
      0.001), whereas patients who did not use the HBP had no significant difference in
      survival (HR = 0.96; 95% CI, 0.78-1.19; p = 0.69). Patients offered the HBP also
      had fewer hospital admissions following enrollment (Delta = -0.05
      admissions/quarter; p = 0.011), which was primarily observed in patients who used
      the HBP at least once (Delta = -0.10 admissions/quarter; p < 0.001). CONCLUSIONS:
      The HBP, a content-driven telehealth system coupled with care management, was
      associated with significantly better survival and reduced hospitalization in
      Medicare beneficiaries with HF. Prospective study is warranted to determine the
      mechanism of this association and opportunities for optimization.

PMID- 26218253
TI  - Bruxism and Dental Implants: A Meta-Analysis.
AB  - PURPOSE: To test the null hypothesis of no difference in the implant failure
      rates, postoperative infection, and marginal bone loss after the insertion of
      dental implants in bruxers compared with the insertion in non-bruxers against the
      alternative hypothesis of a difference. METHODS: An electronic search was
      undertaken in June 2014. Eligibility criteria included clinical studies, either
      randomized or not. RESULTS: Ten publications were included with a total of 760
      implants inserted in bruxers (49 failures; 6.45%) and 2989 in non-bruxers (109
      failures; 3.65%). Due to lack of information, meta-analyses for the outcomes
      "postoperative infection" and "marginal bone loss" were not possible. A risk
      ratio of 2.93 was found (95% confidence interval, 1.48-5.81; P = 0.002).
      CONCLUSIONS: These results cannot suggest that the insertion of dental implants
      in bruxers affects the implant failure rates due to a limited number of published
      studies, all characterized by a low level of specificity, and most of them deal
      with a limited number of cases without a control group. Therefore, the real
      effect of bruxing habits on the osseointegration and survival of endosteal dental
      implants is still not well established.

PMID- 26218255
TI  - Improving Survival and Neurologic Function for Younger Age Groups After Out-of
      Hospital Cardiac Arrest in Sweden: A 20-Year Comparison.
AB  - OBJECTIVE: To describe changes in the epidemiology of out-of-hospital cardiac
      arrest in Sweden with the emphasis on the younger age groups. DESIGN: Prospective
      observational study. SETTING: Sweden. PATIENTS: Patients were recruited from the
      Swedish Registry of Cardiopulmonary Resuscitation from 1990 to 2012. Only non
      crew-witnessed cases were included. INTERVENTION: Cardiopulmonary resuscitation.
      MEASUREMENT AND MAIN RESULTS: The endpoint was 30-day survival. Cerebral function
      among survivors was estimated according to the cerebral performance category
      scores. In all, 50,879 patients in the survey had an out-of-hospital cardiac
      arrest, of which 1,321 (2.6%) were 21 years old or younger and 1,543 (3.0%) were
      22-35 years old. On the basis of results from 2011 and 2012, we estimated that
      there are 4.9 cases per 100,000 person-years in the age group 0-21 years. The
      highest survival was found in the 13- to 21-year age group (12.6%). Among
      patients 21 years old or younger, the following were associated with an increased
      chance of survival: increasing age, male gender, witnessed out-of-hospital
      cardiac arrest, ventricular fibrillation, and a short emergency medical service
      response time. Among patients 21 years old or younger , there was an increase in
      survival from 6.2% in 1992-1998 to 14.0% in 2007-2012. Among 30-day survivors,
      91% had a cerebral performance category score of 1 or 2 (good cerebral
      performance or moderate cerebral disability) at hospital discharge. CONCLUSIONS:
      In Sweden, among patients 21 years old or younger, five out-of-hospital cardiac
      arrests per 100,000 person-years occur and survival in this patient group has
      more than doubled during the past two decades. The majority of survivors have
      good or relatively good cerebral function.

PMID- 26218256
TI  - Targeting Glycemic Control After Pediatric Cardiac Surgery: The Influence of Age
      on Insulin Requirement.
AB  - OBJECTIVE: Factors influencing the development of hyperglycemia and pattern of
      insulin requirement in children undergoing cardiac surgery are poorly understood.
      This study investigated the impact of age on the pattern of hyperglycemia and
      insulin requirement in children after cardiac surgery. DESIGN: Cohort study,
      based on a prospectively collected dataset for patients enrolled into the Control
      of Hyperglycemia in Pediatric Intensive Care trial. SETTING: A 24-bedded
      multidisciplinary PICU. PATIENTS: Children randomized to the tight glycemic
      control arm (target blood glucose, 4-7 mmol/L [72-126 mg/dL]) of the Control of
      Hyperglycemia in Pediatric Intensive Care trial following cardiac surgery.
      Children were categorized into four age groups (neonate, 1-30 d; infant, 31-365
      d; young child, 1-5 yr; older child, 5-16 yr) for analyses of patterns of
      hyperglycemia and insulin requirement over the 12-hour period following
      initiation of insulin. INTERVENTIONS: Insulin titration was performed based on
      blood glucose value and rate of change of blood glucose using an algorithm
      developed for the Control of Hyperglycemia in Pediatric Intensive Care trial.
      MEASUREMENTS AND MAIN RESULTS: Of 92 children, 72 children (78%) randomized to
      the tight glycemic control group developed hyperglycemia (blood glucose, > 7
      mmol/L [126 mg/dL]) and received insulin. Older age was associated with higher
      blood glucose and a higher insulin dose per kilogram over the first 3 hours of
      the study period (p <= 0.02). Cumulative insulin dose was significantly higher in
      older children (median, 1.3 U/kg [range, 0.2-5.75]) compared with other age
      groups (neonate, 0.37 [0.05-2.2]; infant, 0.45 [0.05-2.2]; young child, 0.35
      [0.05-0.81]) (p = 0.004). Age group, rather than body mass index, carbohydrate
      intake, or cardiac surgery variables, was the only variable (coefficient: 1.14 +/
      0.3; p < 0.001) associated with cumulative insulin dose on multivariate
      analysis. CONCLUSIONS: When tight glycemic control is targeted in children who
      have undergone cardiac surgery, children in the older child age group (5-16 yr)
      require insulin at significantly higher doses. Further study is needed to
      understand the mechanisms involved.

PMID- 26218257
TI  - Prevalence and Predictors of Adverse Events during Procedural Sedation Anesthesia
      Outside the Operating Room for Esophagogastroduodenoscopy and Colonoscopy in
      Children: Age Is an Independent Predictor of Outcomes.
AB  - OBJECTIVES: Procedural sedation/anesthesia outside the operating room for a
      variety of procedures is well described with an overall low adverse event rate in
      certain settings. Adverse event associated with procedural sedation/anesthesia
      outside the operating room for gastrointestinal procedures have been described,
      albeit in small, single-center studies with wide variance in outcomes. Predictors
      of such outcomes are unclear. We aimed to estimate the prevalence of adverse
      event in children undergoing procedural sedation/anesthesia outside the operating
      room for esophagogastroduodenoscopy, colonoscopy, or both to identify predictors
      of adverse event. DESIGN/SETTING/PATIENTS: Retrospective analysis of Pediatric
      Sedation Research Consortium database, a large data repository of pediatric
      patients aged 21 years old or younger undergoing procedural sedation/anesthesia
      outside the operating room during September 2007 to November 2011. Twenty-two of
      the 40 centers provided data pertaining to the procedure of interest.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome variable is
      any adverse event. Independent variables include: age (five groups), sex,
      American Societyof Anaesthesiologists status, procedure
      (esophagogastroduodenoscopy, colonoscopy, or both), provider responsible,
      medication used, location, and presence of coexisting medical conditions.
      Descriptive statistics used to summarize the data. Using multivariablelogistic
      regression model, odds ratio, 95% CI) were computed. A total of 12,030 procedures
      were performed (esophagogastroduodenoscopy, 7,970; colonoscopy, 1,378; and both,
      2,682). A total of 96.9% of patients received propofol. Eighty-three percent were
      performed in a sedation unit. Prevalence of adverse event was 4.8%. The most
      common adverse event were persistent desaturations (1.5%), airway obstruction
      (1%), cough (0.9%), and laryngospasm (0.6%). No deaths or CPR occurred. Infants
      and children aged 5 years old or younger had a higher adverse event rate than
      older children (15.8%, 7.8% vs 4%). Regression analysis revealed age 5 years old
      or younger, American Society of Anaesthesiologists greater than or equal to 2,
      esophagogastroduodenoscopy +/- colonoscopy, and coexisting medical conditions of
      obesity and lower airway disease were independent predictors of higher adverse
      event. CONCLUSIONS: Overall prevalence of any adverse event was 4.8%. Independent
      predictors of adverse events in procedural sedation/anesthesia outside the
      operating room in pediatric esophagogastroduodenoscopy/colonoscopy onoscopy were
      identified. Recognition of such risk factors may enable optimization of
      procedural sedation.

PMID- 26218258
TI  - The Value of Screening Parents for Their Risk of Developing Psychological
      Symptoms After PICU: A Feasibility Study Evaluating a Pediatric Intensive Care
      Follow-Up Clinic.
AB  - OBJECTIVES: This study aimed to assess whether prospectively screening parents
      for psychological vulnerability would enable beneficial targeting of a subsequent
      follow-up clinic. DESIGN AND SETTING: Parents of children consecutively admitted
      to a PICU were assessed for risk of developing posttraumatic stress disorder at
      discharge using the Posttraumatic Adjustment Scale. INTERVENTIONS: High-risk
      parents were then randomized to the intervention (follow-up clinic, 2 mo after
      discharge) or control condition. MEASUREMENTS AND MAIN RESULTS: All parents
      completed Impact of Event Scale-Revised and Hospital Anxiety and Depression Scale
      at 6 months. Of the 209 parents of 145 children recruited to the study, 78 (37%)
      were identified, on the basis of their Posttraumatic Adjustment Scale score at
      baseline, as being at risk of developing posttraumatic stress disorder, and
      randomized to the control or intervention condition. Follow-up data were provided
      by 157 of 209 parents (75%). Logistic regression analyses controlling for parent
      gender and child length of stay showed that high-risk control parents (n = 32)
      were significantly more likely to score above the clinical cutoff for all three
      psychological outcomes than parents deemed low risk at baseline (n = 89)
      (posttraumatic stress: odds ratio = 3.39; 95% CI, 1.28-8.92; p = 0.014; anxiety:
      odds ratio = 6.34; 95% CI, 2.55-15.76; p < 0.001; depression: odds ratio = 4.13;
      95% CI, 1.47-11.61; p = 0.007). Only 14 of 38 (37%) high-risk intervention
      parents attended the follow-up clinic appointment they were offered. At follow
      up, there were no statistically significant differences between the intervention
      and control groups, but there were small effect sizes in favor of the
      intervention for anxiety scores (Cohen d = 0.209) and depression scores (Cohen d
      = 0.254) CONCLUSIONS:: Screening parents for psychological vulnerability using
      measures such as the Posttraumatic Adjustment Scale may enable more efficient
      targeting of support. However, further research is needed on how best to provide
      effective follow-up intervention for families.

PMID- 26218259
TI  - Gastric Dysmotility in Critically Ill Children: Pathophysiology, Diagnosis, and
      Management.
AB  - OBJECTIVE: We aimed to review gastric dysmotility in critically ill children: 1)
      its pathophysiology, with a focus on critical care diseases and therapies that
      affect gastric motility, 2) diagnostic methodologies, and 3) current and future
      potential therapies. DATA SOURCES: Eligible studies were identified from PubMed
      and MEDLINE. STUDY SELECTION: Literature search included the following key terms:
      "gastric emptying," "gastric motility/dysmotility," "gastrointestinal
      motility/dysmotility," "nutrition intolerance," and "gastric residual volume."
      DATA EXTRACTION: Studies since 1995 were extracted and reviewed for inclusion by
      the authors related to the physiology, pathophysiology, diagnostic methodologies,
      and available therapies for gastric emptying. DATA SYNTHESIS: Delayed gastric
      emptying, a common presentation of gastric dysmotility, is present in up to 50%
      of critically ill children. It is associated with the potential for aspiration,
      ventilator-associated pneumonia, and inadequate delivery of enteral nutrition and
      may affect the efficacy of enteral medications, all of which may be result in
      poor patient outcomes. Gastric motility is affected by critical illness and its
      associated therapies. Currently available diagnostic tools to identify gastric
      emptying at the bedside have not been systematically studied and applied in this
      cohort. Gastric residual volume measurement, used as an indirect marker of
      delayed gastric emptying in PICUs around the world, may be inaccurate.
      CONCLUSIONS: Gastric dysmotility is common in critically ill children and impacts
      patient safety and outcomes. However, it is poorly understood, inadequately
      defined, and current therapies are limited and based on scant evidence.
      Understanding gastric motility and developing accurate bedside measures and novel
      therapies for gastric emptying are highly desirable and need to be further
      investigated.

PMID- 26218260
TI  - Clinical Epidemiology of Extubation Failure in the Pediatric Cardiac ICU: A
      Report From the Pediatric Cardiac Critical Care Consortium.
AB  - OBJECTIVE: To describe the clinical epidemiology of extubation failure in a
      multicenter cohort of patients treated in pediatric cardiac ICUs. DESIGN:
      Retrospective cohort study using prospectively collected clinical registry data.
      SETTING: Pediatric Cardiac Critical Care Consortium registry. PATIENTS: All
      patients admitted to the CICU at Pediatric Cardiac Critical Care Consortium
      hospitals. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis of all
      mechanical ventilation episodes in the registry from October 1, 2013, to July 31,
      2014. The primary outcome of extubation failure was reintubation less than 48
      hours after planned extubation. Repeated-measures analysis using generalized
      estimating equations to account for within patient and center correlation was
      performed to identify risk factors for extubation failure. Adjusted extubation
      failure rates for each hospital were calculated using logistic regression
      controlling for patient factors. Of 1,734 mechanical ventilation episodes (1,478
      patients at eight hospitals) ending in a planned extubation, there were 100
      extubation failures (5.8%). In multivariable analysis, only longer duration of
      mechanical ventilation was significantly associated with extubation failure (p =
      0.01); the failure rate was 4% when ventilated less than 24 hours, 9% after 24
      hours, and 13% after 7 days. For 503 patients intubated and extubated in the
      cardiac operating room, 15 patients (3%) failed extubation within 48 hours (12
      within 24 hr). Case-mix-adjusted extubation failure rates ranged from 1.1% to
      9.8% across hospitals. Patients failing extubation had greater median cardiac ICU
      length of stay (15 vs 3 d; p < 0.001) and in-hospital mortality (7.9 vs 1.2%; p <
      0.001). CONCLUSIONS: Though extubation failure is uncommon overall, there may be
      opportunities to improve extubation readiness assessment in patients ventilated
      more than 24 hours. These data suggest that extubation in the operating room
      after cardiac surgery can be done with a low failure rate. We observed variation
      in extubation failure rates across hospitals, and future investigation must
      elucidate the optimal strategies of high-performing centers to reduce ventilation
      time while limiting extubation failures.

PMID- 26218261
TI  - Genetic Diversity and Population Structure of Basmati Rice (Oryza sativa L.)
      Germplasm Collected from North Western Himalayas Using Trait Linked SSR Markers.
AB  - One hundred forty one basmati rice genotypes collected from different geographic
      regions of North Western Himalayas were characterized using 40 traits linked
      microsatellite markers. Number of alleles detected by the abovementioned primers
      were 112 with a maximum and minimum frequency of 5 and 2 alleles, respectively.
      The maximum and minimum polymorphic information content values were found to be
      0.63 and 0.17 for the primers RM206 and RM213, respectively. The genetic
      similarity coefficient for the most number of pairs ranged between of 0.2-0.9
      with the average value of 0.60 for all possible combinations, indicating moderate
      genetic diversity among the chosen genotypes. Phylogenetic cluster analysis of
      the SSR data based on distance divided all genotypes into four groups (I, II, III
      and IV), whereas model based clustering method divided these genotypes into five
      groups (A, B, C, D and E). However, the result from both the analysis are in well
      agreement with each other for clustering on the basis of place of collection and
      geographic region, except the local basmati genotypes which clustered into three
      subpopulations in structure analysis comparison to two clusters in distance based
      clustering. The diverse genotypes and polymorphic trait linked microsatellites
      markers in the present study will be used for the identification of quantitative
      trait loci/genes for different economically important traits to be utilized in
      molecular breeding programme of rice in the future. 

PMID- 26218262
TI  - Safety and Efficacy of Intravitreal Preservative-Free Triamcinolone Acetonide
      (Triesence) for Macular Edema.
AB  - PURPOSE: To evaluate the efficacy and safety of preservative-free triamcinolone
      acetonide (Triesence) for the treatment of macular edema. METHODS: A
      retrospective study was conducted on patients who attended a tertiary retinal
      clinic from June 2009 to July 2012 with macular edema due to various causes.
      Patients who received at least 1 intravitreal Triesence injection and completed 6
      months of follow-up were recruited. Data, including best-corrected Snellen visual
      acuity, central macular thickness (CMT), intraocular pressure (IOP), and adverse
      events (AEs), were collected at baseline, week 1, month 1, month 3, and month 6
      after initiation of treatment. Snellen visual acuity was converted to visual
      acuity score (VAS) for statistical analysis using paired t-tests and linear
      regression. RESULTS: One hundred two eyes from 102 patients were included in the
      study. Mean VAS was significantly improved at all follow-up time points compared
      to baseline (P<=0.002), with highest mean gain at month 1 (6.1+/-8.9 letters).
      Mean CMT decreased significantly at all follow-up points compared to baseline
      (P<=0.0005), with the greatest reduction at week 1 (146.6+/-109.4 MUm). A total
      of 22 AEs were observed, and IOP elevation was the most common AE related to
      Triesence treatment (17/22, 77.3%). No sterile or infectious endophthalmitis was
      observed. CONCLUSION: Intravitreal Triesence improves visual acuity and reduces
      macular thickness in eyes with macular edema from various causes. Treatment
      associated IOP elevation was manageable with antiglaucoma medications. There were
      no serious vision-threatening complications associated with intravitreal
      Triesence therapy during the study period.

PMID- 26218263
TI  - Implementation of Cell Samples as Controls in National Proficiency Testing for
      Clopidogrel Therapy-Related CYP2C19 Genotyping in China: A Novel Approach.
AB  - Laboratories are increasingly requested to perform CYP2C19 genetic testing when
      managing clopidogrel therapy, especially in patients with acute coronary syndrome
      undergoing percutaneous coronary intervention. To ensure high quality molecular
      testing and ascertain that the referring clinician has the correct information
      for CYP2C19 genotype-directed antiplatelet therapy, a proficiency testing scheme
      was set up to evaluate the laboratory performance for the entire testing process.
      Proficiency panels of 10 cell samples encompassing the common CYP2C19 genetic
      polymorphisms were distributed to 62 participating laboratories for routine
      molecular testing and the responses were analyzed for accuracy of genotyping and
      the reporting of results. Data including the number of samples tested, the
      accreditation/certification status, and test methodology of each individual
      laboratory were also reviewed. Fifty-seven of the 62 participants correctly
      identified the CYP2C19 variants in all samples. There were six genotyping errors,
      with a corresponding analytical sensitivity of 98.5% (333/338 challenges; 95%
      confidence interval: 96.5-99.5%) and an analytic specificity of 99.6% (281/282;
      95% confidence interval: 98.0-99.9%). Reports of the CYP2C19 genotyping results
      often lacked essential information. In conclusion, clinical laboratories
      demonstrated good analytical sensitivity and specificity; however, the
      pharmacogenetic testing community requires additional education regarding the
      correct reporting of CYP2C19 genetic test results. 

PMID- 26218265
TI  - Fabrication of Sub-25 nm Diameter GaSb Nanopillar Arrays by Nanoscale Self-Mask
      Effect.
AB  - GaSb individual nanowires and nanowire arrays are considered as intriguing
      candidates for electronic and photonic applications. In this paper, we report a
      new mask-free method to fabricate large area GaSb nanopillar arrays through
      reactive ion etching of GaSb substrates facilitated by O2 plasma. We have shown
      that nanoscale oxide self-masks could form thereby facilitating the formation of
      GaSb nanopillars. We have achieved GaSb nanowires with diameters less than 25 nm
      and an aspect ratio of 24. Additionally, GaSb nanopillar arrays with desired
      heights, diameters, and density can be obtained by choosing the plasma chemistry
      and/or controlling etching parameters, such as bias power and pressure. The
      nanopillar arrays prepared also exhibit tunable broadband antireflection
      properties. 

PMID- 26218264
TI  - Fragment-Based Drug Discovery Targeting Inhibitor of Apoptosis Proteins:
      Discovery of a Non-Alanine Lead Series with Dual Activity Against cIAP1 and XIAP.
AB  - Inhibitor of apoptosis proteins (IAPs) are important regulators of apoptosis and
      pro-survival signaling pathways whose deregulation is often associated with tumor
      genesis and tumor growth. IAPs have been proposed as targets for anticancer
      therapy, and a number of peptidomimetic IAP antagonists have entered clinical
      trials. Using our fragment-based screening approach, we identified nonpeptidic
      fragments binding with millimolar affinities to both cellular inhibitor of
      apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP).
      Structure-based hit optimization together with an analysis of protein-ligand
      electrostatic potential complementarity allowed us to significantly increase
      binding affinity of the starting hits. Subsequent optimization gave a potent
      nonalanine IAP antagonist structurally distinct from all IAP antagonists
      previously reported. The lead compound had activity in cell-based assays and in a
      mouse xenograft efficacy model and represents a highly promising start point for
      further optimization. 

PMID- 26218266
TI  - Snapping Thumb and Superficial Radial Nerve Entrapment in De Quervain Disease:
      Ultrasound Imaging/Guidance Revisited.

PMID- 26218267
TI  - Is Autophagy Altered in the Leukocytes of Type 2 Diabetic Patients?
AB  - It is unknown whether autophagy is altered in the leukocytes of type 2 diabetes
      (T2D) patients and whether oxidative and endoplasmic reticulum (ER) stresses
      regulate this mechanism. We studied anthropometric and metabolic parameters and
      evaluated oxidative stress, chromatin condensation, ER stress, and autophagy
      parameters in leukocytes of 103 T2D patients versus 109 sex- and age-matched
      controls. Patients showed increases in glucose, insulin, homeostasis model
      assessment of insulin resistance, and glycated hemoglobin (HbA1c) compared with
      controls (p < 0.001). Leukocytes displayed enhanced total and mitochondrial
      reactive oxygen species (ROS), reduced mitochondrial mass, and increased
      chromatin condensation (p < 0.05). ER stress was also activated in diabetic
      patients, who displayed augmented glucose-regulated protein 78 kDa (GRP78),
      phosphorylated eukaryotic translation initiation factor 2, subunit 1 alpha (P
      eIF2alpha), and activating transcription factor 6 (ATF6) levels (p < 0.05). We
      also observed an increase in the autophagy markers, microtubule-associated
      protein light chain 3 (LC3)-II and Beclin 1 (p < 0.05), and significant positive
      correlations between Beclin 1 and total ROS (r = 0.667), GRP78 (r = 0.925) and P
      eIF2alpha (r = 0.644), and between LC3-II and P-eIF2alpha (r = 0.636) and ATF6 (r
      = 0.601). Our results lead to the hypothesis that autophagy is activated in the
      leukocytes of T2D patients and that both oxidative and ER stress signaling
      pathways may be implicated in the induction of autophagy.

PMID- 26218269
TI  - BaFe12O19-chitosan Schiff-base Ag (I) complexes embedded in carbon nanotube
      networks for high-performance electromagnetic materials.
AB  - The multiwalled carbon nanotubes/BaFe12O19-chitosan (MCNTs/BF-CS) Schiff base Ag
      (I) complex composites were synthesized successfully by a chemical bonding
      method. The morphology and structures of the composites were characterized with
      electron microscopy, Fourier transform infrared spectroscopy and X-ray
      diffraction techniques. Their conductive properties were measured using a four
      probe conductivity tester at room temperature, and their magnetic properties were
      tested by a vibrating sample magnetometer. The results show that the BF-CS Schiff
      base Ag (I) complexes are embedded into MCNT networks. When the mass ratio of
      MCNTs and BF-CS Schiff base is 0.95:1, the conductivity, Ms (saturation
      magnetization), Mr (residual magnetization), and Hc (coercivity) of the BF-CS
      Schiff base composites reach 1.908 S cm(-1), 28.20 emu g(-1), 16.66 emu g(-1) and
      3604.79 Oe, respectively. Finally, a possible magnetic mechanism of the
      composites has also been proposed.

PMID- 26218270
TI  - Checkpoint Activation of an Unconventional DNA Replication Program in
      Tetrahymena.
AB  - The intra-S phase checkpoint kinase of metazoa and yeast, ATR/MEC1, protects
      chromosomes from DNA damage and replication stress by phosphorylating subunits of
      the replicative helicase, MCM2-7. Here we describe an unprecedented ATR-dependent
      pathway in Tetrahymena thermophila in which the essential pre-replicative complex
      proteins, Orc1p, Orc2p and Mcm6p are degraded in hydroxyurea-treated S phase
      cells. Chromosomes undergo global changes during HU-arrest, including
      phosphorylation of histone H2A.X, deacetylation of histone H3, and an apparent
      diminution in DNA content that can be blocked by the deacetylase inhibitor sodium
      butyrate. Most remarkably, the cell cycle rapidly resumes upon hydroxyurea
      removal, and the entire genome is replicated prior to replenishment of ORC and
      MCMs. While stalled replication forks are elongated under these conditions, DNA
      fiber imaging revealed that most replicating molecules are produced by new
      initiation events. Furthermore, the sole origin in the ribosomal DNA
      minichromosome is inactive and replication appears to initiate near the rRNA
      promoter. The collective data raise the possibility that replication initiation
      occurs by an ORC-independent mechanism during the recovery from HU-induced
      replication stress. 

PMID- 26218272
TI  - Editorial Comment for Abreu et al.

PMID- 26218271
TI  - Tolerance and Cross-Tolerance following Toll-Like Receptor (TLR)-4 and -9
      Activation Are Mediated by IRAK-M and Modulated by IL-7 in Murine Splenocytes.
AB  - OBJECTIVE: Immune suppression during critical illness predisposes to serious
      infections. We sought to determine the mechanisms regulating tolerance and cross
      tolerance to common pro-inflammatory danger signals in a model that recapitulates
      the intact in vivo immune response. MATERIALS AND METHODS: Flt3-expanded
      splenocytes obtained from wild-type or matching IRAK-M knockout (IRAK-M-/-),
      C57BL/6, male mice (8-10 weeks old) were treated repeatedly or alternately with
      either LPS or CpGA DNA, agonists of Toll-like receptor (TLR)-4 and -9,
      respectively, over successive 24-hour periods. Supernatants were collected
      following each 24-hour period with cytokine release (ELISA) and splenocyte IRAK-M
      expression (Western blot) determined. Tolerance and cross-tolerance were assessed
      in the absence or presence of programmed death receptor (PD)-1 blocking antibody
      or IL-7 pre-treatment. MAIN RESULTS: Splenocytes notably exhibited both tolerance
      and cross-tolerance to subsequent treatments with either LPS or CpGA DNA. The
      character of tolerance and cross-tolerance in this model was distinct following
      initial LPS or CpGA treatment in that TNFalpha and IFNgamma release (not IL-10)
      were suppressed following LPS; whereas, initial CpGA treatment suppressed
      TNFalpha, IFNgamma and IL-10 release in response to subsequent stimulation (LPS
      or CpGA). Tolerance and cross-tolerance were unrelated to IL-10 release or PD-1
      but were attenuated in IRAK-M-/- splenocytes. IL-7 significantly suppressed IRAK
      M expression and restored TNFalpha and IFNgamma production without influencing IL
      10 release. CONCLUSIONS: In summary, acute immune tolerance and cross-tolerance
      in response to LPS or CpGA were distinct in that LPS selectively suppressed pro
      inflammatory cytokine responses; whereas, CpGA suppressed both pro- and anti
      inflammatory responses. The induction of tolerance and cross-tolerance in
      response to common danger signals was mechanistically unrelated to IL-10 or PD-1
      but was directly influenced by IRAK-M expression. IL-7 reduced IRAK-M expression
      and attenuated immune tolerance induced by either LPS or CpGA, and thus may be
      useful for reversal of immune tolerance in the setting of critical illness.

PMID- 26218273
TI  - The Demethylase Activity of FTO (Fat Mass and Obesity Associated Protein) Is
      Required for Preadipocyte Differentiation.
AB  - FTO (fat mass and obesity associated gene) was genetically identified to be
      associated with body mass index (BMI), presumably through functional regulation
      of energy homeostasis. However, the cellular and molecular mechanisms by which
      FTO functions remain largely unknown. Using 3T3-L1 preadipocyte as a model to
      study the role of FTO in adipogenesis, we demonstrated that FTO is functionally
      required for 3T3-L1 differentiation. FTO knock-down with siRNA inhibited
      preadipocyte differentiation, whereas ectopic over-expression of FTO enhanced the
      process. The demethylase activity of FTO is required for differentiation. Level
      of N6-methyladenosine (m6A) is decreased in cells over-expressing FTO. In
      contrast, overexpression of R96Q, a FTO missense mutant lack of demethylase
      activity, had no effect on cellular m6A level and impeded differentiation.
      Treatment with Rosiglitazone, a PPARgamma agonist, could overcome the
      differentiation inhibition imposed by R96Q mutant, suggesting the effect of FTO
      is mediated through PPARgamma. 

PMID- 26218275
TI  - Effects of Simulated Nitrogen Deposition on Soil Net Nitrogen Mineralization in
      the Meadow Steppe of Inner Mongolia, China.
AB  - Effects of simulated nitrogen (N) deposition on soil net nitrogen mineralization
      (NNM) were examined in situ during two growing seasons, using the resin-core
      technique in the semiarid meadow steppe in Inner Mongolia, China. The aim of this
      study is to clarify the effect of N levels (0, 10, and 20 kg N ha-1yr-1) and
      forms (NH4+ and NO3-) on soil mineral N and NNM. Our results showed that N levels
      had no significant differences on soil mineral N and NNM. In the first year,
      three N treatments ((NH4)2SO4, NH4Cl and KNO3) increased soil NH4+ concentrations
      but had no significant effects on soil NO3- concentrations. In the second year,
      (NH4)2SO4 treatment increased soil NO3- concentrations, NH4Cl and KNO3 treatments
      decreased them. Three N treatments significantly decreased soil NH4+
      concentrations in the later stages of the second year. As for the soil NNM, three
      N treatments had no significant effects on the rates of soil NNM (Rm) and net
      nitrification (Rn) in the first year, but significantly decreased them in the
      second year. The contribution of N addition to Rm was higher from (NH4)2SO4 than
      from NH4Cl and KNO3. However, Soil Rm was mainly affected by soil water content
      (SWC), accumulated temperature (Ta), and soil total N (TN). These results suggest
      that the short-term atmospheric N deposition may inhibit soil NNM in the meadow
      steppe of Inner Mongolia. 

PMID- 26218276
TI  - Sensitivity and robustness enhancements by using a V-shape ion funnel in FTICR
      MS.
AB  - In this paper, a new configuration of the ion funnel interface (i.e., V-shape ion
      funnel (V-IF)) for high ion transmission efficiency and robustness enhancement
      was developed and implemented on FTICR-MS. The performance of the V-IF was
      compared with that of a home-built orthogonal ion funnel. An order of magnitude
      of improvement in sensitivity was achieved for various peptides and proteins. The
      performance of the instrument was maintained for a long period by neutral
      molecule removal. Other ion transmission patterns, such as gentle ion
      transmission, adduct ion removal, and radio frequency (RF)-driven collision
      induced dissociation (CID), was also realized in V-IF by varying the RF
      potentials. V-IF is believed to be a novel ion guide that has promising
      applications in mass spectrometry. 

PMID- 26218274
TI  - Admission Risk Score to Predict Inpatient Pediatric Mortality at Four Public
      Hospitals in Uganda.
AB  - Mortality rates among hospitalized children in many government hospitals in sub
      Saharan Africa are high. Pediatric emergency services in these hospitals are
      often sub-optimal. Timely recognition of critically ill children on arrival is
      key to improving service delivery. We present a simple risk score to predict
      inpatient mortality among hospitalized children. Between April 2010 and June
      2011, the Uganda Malaria Surveillance Project (UMSP), in collaboration with the
      National Malaria Control Program (NMCP), set up an enhanced sentinel site malaria
      surveillance program for children hospitalized at four public hospitals in
      different districts: Tororo, Apac, Jinja and Mubende. Clinical data collected
      through March 2013, representing 50249 admissions were used to develop a
      mortality risk score (derivation data set). One year of data collected
      subsequently from the same hospitals, representing 20406 admissions, were used to
      prospectively validate the performance of the risk score (validation data set).
      Using a backward selection approach, 13 out of 25 clinical parameters
      recognizable on initial presentation, were selected for inclusion in a final
      logistic regression prediction model. The presence of individual parameters was
      awarded a score of either 1 or 2 based on regression coefficients. For each
      individual patient, a composite risk score was generated. The risk score was
      further categorized into three categories; low, medium, and high. Patient
      characteristics were comparable in both data sets. Measures of performance for
      the risk score included the receiver operating characteristics curves and the
      area under the curve (AUC), both demonstrating good and comparable ability to
      predict deathusing both the derivation (AUC =0.76) and validation dataset (AUC
      =0.74). Using the derivation and validation datasets, the mortality rates in each
      risk category were as follows: low risk (0.8% vs. 0.7%), moderate risk (3.5% vs.
      3.2%), and high risk (16.5% vs. 12.6%), respectively. Our analysis resulted in
      development of a risk score that ably predicted mortality risk among hospitalized
      children. While validation studies are needed, this approach could be used to
      improve existing triage systems. 

PMID- 26218277
TI  - Arg25Pro (c.915G>C) polymorphism of transforming growth factor beta1 gene
      suggests an association with increased risk for Hashimoto's thyroiditis.
AB  - BACKGROUND: The etiopathogenesis of Hashimoto's thyroiditis (HT) - has not been
      clearly elucidated although the role of chronic inflammation, endothelial
      dysfunction, and imbalance between pro- and anti-inflammatory cytokines has been
      established. Transforming growth factor beta1 (TGFbeta1) is required to maintain
      immune homeostasis, and is implicated in lymphocyte infiltration, production of
      autoantibodies and thyrocyte destruction seen in patients with HT. AIM: The aim
      of the present study was to investigate the possible association of Leu10Pro
      (c.869T>C) and Arg25Pro (c.915G>C) single nucleotide polymorphisms (SNPs) of
      TGFbeta1 gene with the occurrence of HT. METHODS: We analyzed the genotype and
      allele frequencies of polymorphisms at codon 10 and 25 in 178 patients who had
      been diagnosed as having HT and 197 healthy controls using PCR-restriction
      fragment length polymorphism (RFLP). RESULTS: There was no notable risk for HT
      afflicted by Leu10Pro (c.869T>C) polymorphism of TGFbeta1 gene. However, there
      was a significant increase of Arg25Pro (c.915G>C) C allele frequency in patients
      with HT compared with healthy controls (p=0.003, OR=1.87, 95% CI=1.23-2.84).
      Moreover, heterozygous (CG) subjects had a 2.53-fold increased risk for
      developing HT with respect to wild (GG) homozygotes (p<0.001, 95% CI=1.57-4.05).
      TSH levels in CG heterozygous patients were increased in comparison with wild
      homozygotes (p=0.006). CONCLUSION: This study indicates that the Arg25Pro
      (c.915G>C) polymorphism of TGFbeta1 gene may be related to increased risk for HT.

PMID- 26218278
TI  - Overexpression of CRY1 protects against the development of atherosclerosis via
      the TLR/NF-kappaB pathway.
AB  - It has been demonstrated that the circadian clock system could be a potential
      factor involved in inflammation and the progression of atherosclerosis. A
      previous study has reported that cryptochrome 1 (CRY1), which is a core clock
      component, is associated with regulating proinflammation. However, whether CRY1
      is involved in atherosclerosis is currently unknown. In the present study, we
      aimed to explore the role of CRY1 in regulating atherosclerosis in apolipoprotein
      E (ApoE)-deficient mice and the underlying molecular mechanism. We found that
      CRY1 mRNA expression was significantly decreased in atherosclerotic patients
      compared to the healthy subjects. Overexpression of CRY1 in the mouse model of
      atherosclerosis by adenovirus-mediated gene transfer significantly decreased the
      expression of proinflammatory factors including tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL)-1, IL-6, and macrophage inflammatory protein-1alpha (MIP
      1alpha). In addition, the adhesion molecules including vascular cell adhesion
      molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin,
      were also downregulated by CRY1 overexpression. Furthermore, the plaque area of
      the aortic sinus and the concentrations of total cholesterol (TC), triglyceride
      (TG), and low density lipoprotein cholesterol (LDL-C) were also decreased in the
      atherosclerotic mice by CRY1 overexpression. Moreover, overexpression of CRY1
      significantly decreased the protein levels of toll-like receptor (TLR) 2, TLR4
      and phosphorylated p65 (p-p65). Additionally, the results of luciferase reporter
      assay exhibited that CRY1 overexpression was capable of inhibiting the activation
      of nuclear factor-kappa B (NF-kappaB). Taken together, our results suggest that
      overexpression of CYR1 relieves the development of atherosclerosis that may be
      associated with regulating the TLR/NF-kappaB pathway. 

PMID- 26218279
TI  - Quercetin protects mouse liver against CCl4-induced inflammation by the TLR2/4
      and MAPK/NF-kappaB pathway.
AB  - Quercetin (QE), a natural flavonoid, has many medical beneficial effects.
      However, its protective effects against carbon tetrachloride (CCl4) induced
      injury in liver have not been clarified. The aim of the present study is to
      illustrate the effects of QE on hepatic oxidative injury and inflammation in mice
      exposed to CCl4. ICR (Institute of Cancer Research) mice were exposed to CCl4
      with or without QE co-administration for one week. Our results showed that QE
      administration significantly inhibited CCl4-induced liver injury. One of the
      potential mechanisms of QE action was decreasing the oxidative stress, which is
      consistent with decreasing of lipid peroxidation level and increasing the
      antioxidant enzyme activities in livers of mice. Furthermore, QE significantly
      decreased cytochrome P450 2E1 (CYP2E1) expression and production of pro
      inflammatory markers such as inducible nitric oxide synthase (iNOS), interleukin
      1beta (IL-1beta), cyclooxygenase-2 (COX-2) and nitric oxide (NO) in livers of
      CCl4-treated mouse. In the process of exploring the underlying mechanisms of QE
      action, we found that QE significantly inhibited the Toll-like receptor 2 (TLR2)
      and the Toll-like receptor 4 (TLR4) activation and mitogen-activated protein
      kinase (MAPK) phosphorylation, which in turn inactivated NF-kappaB and the
      inflammatory cytokines in livers of the CCl4-treated mice. In conclusion, these
      results suggested that the inhibition of CCl4-induced inflammation by QE is due
      to its anti-oxidant activity and its ability to modulate the TLR2/TLR4 and
      MAPK/NF-kappaB signaling pathway. 

PMID- 26218280
TI  - Stearoyl lysophosphatidylcholine prevents lipopolysaccharide-induced
      extracellular release of high mobility group box-1 through AMP-activated protein
      kinase activation.
AB  - Previous studies have suggested that stearoyl lysophosphatidlycholine (LPC)
      protects against lethal experimental sepsis by inhibiting lipopolysaccharide
      (LPS)-induced extracellular release of high-mobility group box 1 (HMGB1).
      However, limited information exists on the mechanism by which stearoyl-LPC
      suppresses the extracellular release of HMGB1 in monocyte/macrophages stimulated
      with LPS. In this study, we found that stearoyl-LPC increased the phosphorylation
      of AMP-activated protein kinase (AMPK) in macrophages. Exposure of LPS-stimulated
      macrophages to stearoyl-LPC decreased the extracellular release of HMGB1 in
      peritoneal macrophages, which were inhibited by the AMPK inhibitor, compound C.
      In addition, stearoyl-LPC-mediated suppression of HMGB1 release was abolished by
      siRNA-mediated knock-down of AMPKalpha1. Stearoyl-LPC increased the
      phosphorylation of acetyl-CoA carboxylase (ACC), a downstream target of activated
      AMPK, in mice lungs and decreased HMGB1 levels in bronchoalveolar lavage fluids
      in mice administered LPS. These results reveal a novel mechanism by which
      stearoyl-LPC regulates LPS-mediated cellular translocation of HMGB1. 

PMID- 26218281
TI  - Puerarin attenuates smoke inhalation injury by regulation of Th1/Th2 expression
      and inhibition of Th17 cells in rats.
AB  - OBJECTIVE: Puerarin, a kind of traditional Chinese medicine, possesses
      immunomodulatory property. However, the immunomodulatory effects of puerarin on
      smoke inhalation injury have not been determined. The aim of the current study
      was to investigate the therapeutic efficacy of puerarin on gunpowder smog-induced
      acute lung injury in rats via regulation of Th1/Th2/Th17 expression. MATERIALS
      AND METHODS: Wistar rats were equally randomized to four groups (normal control
      group, puerarin control group, smoke inhalation injury group, puerarin treatment
      plus smoke inhalation injury group). The severity of lung injury was evaluated by
      histopathology, myeloperoxidase (MPO) activity in lung homogenates, cell counting
      in bronchoalveolar lavage fluid (BALF), and lung vascular permeability parameters
      including lung wet to dry weight ratio and protein concentration in BALF. Flow
      cytometry was used to analyze the expression of Th1/Th2/Th17 lymphocytes in blood
      of rats. RESULTS: Puerarin showed significant therapeutic effects against
      neutrophil infiltration and tissue injury, as evidenced by histopathological
      findings and MPO activity. Lung vascular permeability was also relieved by
      puerarin administration. Additionally, puerarin significantly decreased the
      number of neutrophils and lymphocytes in BALF compared with smoke inhalation
      injury group. Furthermore, puerarin increased Th1 immunity and reduced Th2 and
      Th17 responses and thereby altering the Th1/Th2/Th17 imbalance induced by smoke
      inhalation. CONCLUSIONS: Our findings suggested that puerarin suppressed
      inflammatory responses in gunpowder smog-induced acute lung injury by regulation
      of Th1/Th2/Th17 expression, and may be a potential therapeutic agent for smoke
      inhalation injury.

PMID- 26218282
TI  - The pentavalent antimonial therapy against experimental Leishmania amazonensis
      infection is more effective under the inhibition of the NF-kappaB pathway.
AB  - During Leishmania infection, host immune response is important to prevent the
      growth/survival of intracellular amastigotes. In this study, we evaluated in
      vitro and in vivo whether or not during Leishmania amazonensis infection,
      pentavalent antimonial treatment/therapy could be more effective under TNF-alpha
      inhibition. Both L. amazonensis-infected macrophages (in vitro model) and mice
      (in vivo model) were treated with a nuclear factor-kappaB (NF-kappaB) inhibitor
      and with Glucantime(r), alone and in combined administrations. The in vitro
      amastigote counts, cytokines and nitrites' production were assessed after 48h
      incubation with the drugs. Paw lesion sizes and amastigote counts were also
      evaluated in vivo. Quantification of IL-1beta from the infected tissue was
      performed. In vitro results show that when infected macrophages were incubated
      with QNZ+Glucantime(r), a greater clearance was observed for the amastigotes'
      growth and this was related to greater nitrite production compared to the group
      that was only infected. In vivo results show that mice that received the combined
      treatment had their paw lesion sizes and amastigote nests inside the macrophages
      greatly diminished, correlating with increased IL-1beta levels. 

PMID- 26218283
TI  - First-Pass Meconium Samples from Healthy Term Vaginally-Delivered Neonates: An
      Analysis of the Microbiota.
AB  - BACKGROUND: Considerable effort has been made to categorise the bacterial
      composition of the human gut and correlate findings with gastrointestinal
      disease. The infant gut has long been considered sterile at birth followed by
      rapid colonisation; however, this view has recently been challenged. We examined
      first-pass meconium from healthy term infants to confirm or refute sterility.
      METHODS: Healthy mothers were approached following vaginal delivery. First-pass
      meconium stools within 24 hours of delivery were obtained from healthy, breastfed
      infants with tight inclusion/exclusion criteria including rejecting any known
      antibiotic exposure - mother within 7 days preceding delivery or infant after
      birth. Stools were processed in triplicate for fluorescent in-situ hybridisation
      (FISH) with 16S rRNA-targeted probes including Bifidobacterium; Bacteroides
      Prevotella; Lactobacillaceae/Enterococcaceae; Enterobacteriaceae;
      Streptococcaceae; Staphylococcaceae and Enterococcaceae. Absolute counts of all
      bacteria and proportional identification of each bacterial group were calculated.
      Confirmation of bacterial presence by PCR was undertaken on FISH-positive
      samples. RESULTS: The mothers of 31 newborn infants were recruited, 15 met
      inclusion/exclusion criteria and provided a sample within 24 hours of birth,
      processed in the lab within 4 hours. All babies were 37-40 weeks gestation. 8/15
      were male, mean birth weight was 3.4 kg and mean maternal age was 32 years.
      Meconium samples from 10/15 (66%) infants had evidence of bacteria based on FISH
      analysis. Of these, PCR was positive in only 1. Positive FISH counts ranged from
      2.2-41.8 x 10(4) cells/g with a mean of 15.4 x 10(4) cells/g. (The limit of
      detection for automated counting is 10(6) cells/g). Cell counts were too low to
      allow formal diversity analysis. Amplification by PCR was not possible despite
      positive spiked samples demonstrating the feasibility of reaction. One baby was
      dominated by Enterobacteriaceae. The others contained 2-5 genera, with
      Bifidobacterium, Enterobacteriaceae, Enterococcaceae and Bacteroides-Prevotella
      the most prevalent. There was no association between bacterial counts and rupture
      of membrane duration, time to passage of meconium or time to lab. CONCLUSION:
      This study provides evidence that low numbers of bacteria are present in first
      pass meconium samples from healthy, vaginally-delivered, breastfed term infants.
      Only two-thirds of meconium samples had detectable bacteria, though at levels too
      low for automated counting or for reliable confirmation by PCR. This study
      suggests that gut bacterial colonisation is extremely limited at birth and occurs
      rapidly thereafter.

PMID- 26218285
TI  - Reduced Let-7a Is Associated with Chemoresistance in Primary Breast Cancer.
AB  - Chemotherapy resistance remains an important problem in the breast cancer clinic.
      The ability to predict the patients who would respond to a distinct therapy would
      help to optimize tailored treatment options. miRNAs can mediate a number of genes
      in response to drug-induced acute cellular stress. Several studies suggest that
      let-7 miRNA may be involved in the chemosensitivity of cancer cell lines in
      vitro. However, it is not known whether this phenomenon occurs in clinical breast
      tumors. The present study showed that lower let-7a expression was associated with
      epirubicin resistance in primary breast tumors. Moreover, upregulation of let-7a
      expression sensitized resistant breast tumor cell lines to epirubicin by
      enhancing cellular apoptosis in vitro. Collectively, these findings indicate that
      lower expression of let-7a miRNA can induce chemoresistance in breast cancer by
      enhancing cellular apoptosis and suggest that let-7a may be used as a therapeutic
      target to modulate epirubicin-based chemotherapy resistance. 

PMID- 26218284
TI  - Orally Administered Enoxaparin Ameliorates Acute Colitis by Reducing Macrophage
      Associated Inflammatory Responses.
AB  - Inflammatory bowel diseases, such as ulcerative colitis, cause significant
      morbidity and decreased quality of life. The currently available treatments are
      not effective in all patients, can be expensive and have potential to cause
      severe side effects. This prompts the need for new treatment modalities.
      Enoxaparin, a widely used antithrombotic agent, is reported to possess anti
      inflammatory properties and therefore we evaluated its therapeutic potential in a
      mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by
      administration of dextran sulfate sodium (DSS). Mice were treated once daily with
      enoxaparin via oral or intraperitoneal administration and monitored for colitis
      activities. On termination (day 8), colons were collected for macroscopic
      evaluation and cytokine measurement, and processed for histology and
      immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin
      significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice
      retained their body weight and displayed less diarrhea and fecal blood loss
      compared to the untreated colitis group. Colon weight in enoxaparin-treated mice
      was significantly lower, indicating reduced inflammation and edema. Histological
      examination of untreated colitis mice showed a massive loss of crypt architecture
      and goblet cells, infiltration of immune cells and the presence of edema, while
      all aspects of this pathology were alleviated by oral enoxaparin. Reduced number
      of macrophages in the colon of oral enoxaparin-treated mice was accompanied by
      decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly
      reduces the inflammatory pathology associated with DSS-induced colitis in mice
      and could therefore represent a novel therapeutic option for the management of
      ulcerative colitis. 

PMID- 26218286
TI  - Baseline C-Reactive Protein Levels and Life Prognosis in Parkinson Disease.
AB  - BACKGROUND: C-reactive protein (CRP) is a biomarker of inflammation, and high
      levels of CRP correlate with vascular death. Chronic inflammation is considered
      to be involved in neurodegeneration, although there is no evidence linking it
      with the process of neurodegenerative diseases. OBJECTIVE: To determine the role
      of baseline CRP levels in the prognosis of patients with Parkinson disease (PD).
      METHODS: A cohort of 313 patients with a mean age of 69.1 and mean PD duration of
      7.9 years was retrospectively followed for a mean observation time of 1,753 days.
      CRP was measured when patients were not diagnosed with any infections, and levels
      were repetitively measured to investigate a tendency of "regression to mean." The
      primary outcome measure was a survival time from study enrollment to death.
      RESULTS: During the observation period 56 patients died. Baseline CRP was log
      linearly associated with a risk of death in PD. Mean survival time was 3,149 (95%
      confidence interval; 3,009-3,289) days in patients with CRP <= 0.8mg/L (lower two
      thirds) and 2,620 (2,343-2,897) days in those with CRP > 0.8 mg/L (top third, p <
      0.001, log-rank test). The adjusted hazard ratio (HR) per two-fold higher CRP
      concentration for all deaths was 1.29 (1.10-1.52), and after excluding PD
      unrelated deaths, such as cancer or stroke, HR was 1.23 (1.01-1.49) (adjusted for
      age, sex, PD duration, modified Hohen-Yahr stages, MMSE scores, and serum
      albumin). CONCLUSIONS: Baseline CRP concentrations were associated with the risk
      of death and predicted life prognosis of patients with PD. The associations were
      independent from PD duration, PD severity, cognitive function, ages, and
      nutritional conditions, suggesting the possibility that subclinical chronic
      inflammation is associated with a neurodegenerative process in PD.

PMID- 26218287
TI  - Towards better understanding of lipophilicity: assessment of in silico and
      chromatographic logP measures for pharmaceutically important compounds by
      nonparametric rankings.
AB  - Lipophilicity is one of the most frequently used physicochemical properties that
      affects compound solubility, determines its passive transport through biological
      membranes, influences biodistribution, metabolism and pharmacokinetics. We
      compared, ranked and grouped chromatographic lipophilicity indices and
      computationally estimated logP-s by sensitive and robust non-parametric
      approaches: sum of ranking differences (SRD) and generalized pairwise correlation
      method (GPCM). Chromatographic indices of fourteen neurotoxins and twenty one
      1,2,4-triazole compounds have been derived from typical reversed-phase thin-layer
      chromatography and micellar chromatography. They were compared with in silico
      estimated logP-s. Under typical reversed-phase conditions, octadecyl-, octyl-,
      and cyanopropyl-modified silica have clear advantage over ethyl-, aminopropyl-,
      and diol-modified beds, i.e., the preferable choice of the stationary phase
      follows this order:
      octadecyl>octyl>cyanopropyl>ethyl>octadecylwettable>aminopropyl>diol. Many of
      these indices outperform the majority of computationally estimated logP-s. Clear
      distinction can be made based on cross-validation and statistical tests.
      Oppositely, micellar chromatography may not be successfully used for the
      lipophilicity assessment, since retention parameters obtained from the typical
      reversed-phase conditions outperform the parameters obtained by micellar
      chromatography. Both ranking approaches, SRD and GPCM, although based on
      different background, provide highly similar variable ordering and grouping
      leading to the same, above mentioned conclusions. However, GPCM results in more
      degeneracy, i.e., in some cases it cannot distinguish the lipophilicity
      parameters whereas SRD and its cross-validated version can. On the other hand
      GPCM produces a more characteristic grouping. Both methods can be successfully
      used for selection of the most and least appropriate lipophilicity measures.

PMID- 26218289
TI  - Correction: Identification of Candidate Adherent-Invasive E. coli Signature
      Transcripts by Genomic/Transcriptomic Analysis.

PMID- 26218288
TI  - Amyloid-beta(25-35) Modulates the Expression of GirK and KCNQ Channel Genes in
      the Hippocampus.
AB  - During early stages of Alzheimer's disease (AD), synaptic dysfunction induced by
      toxic amyloid-beta (Abeta) is present before the accumulation of
      histopathological hallmarks of the disease. This scenario produces impaired
      functioning of neuronal networks, altered patterns of synchronous activity and
      severe functional deficits mainly due to hyperexcitability of hippocampal
      networks. The molecular mechanisms underlying these alterations remain unclear
      but functional evidence, shown by our laboratory and others, points to the
      involvement of receptors/channels which modulate neuronal excitability, playing a
      pivotal role in early Abeta-induced AD pathogenesis. In particular, two potassium
      channels that control neuronal excitability, G protein-coupled activated inwardly
      rectifying potassium channel (GirK), and voltage-gated K channel (KCNQ), have
      been recently linked to Abeta pathophysiology in the hippocampus. Specifically,
      by using Abeta25-35, we previously found that GirK conductance is greatly
      decreased in the hippocampus, and similar effects have also been reported on KCNQ
      conductance. Thus, in the present study, our goal was to determine the effect of
      Abeta on the transcriptional expression pattern of 17 genes encoding
      neurotransmitter receptors and associated channels which maintain excitatory
      inhibitory neurotransmission balance in hippocampal circuits, with special focus
      in potassium channels. For this purpose, we designed a systematic and reliable
      procedure to analyze mRNA expression by reverse transcriptase quantitative
      polymerase chain reaction (RT-qPCR) in hippocampal rat slices incubated with
      Abeta25-35. We found that: 1) Abeta down-regulated mRNA expression of ionotropic
      GluN1 and metabotropic mGlu1 glutamate receptor subunits as previously reported
      in other AD models; 2) Abeta also reduced gene expression levels of GirK2, 3, and
      4 subunits, and KCNQ2 and 3 subunits, but did not change expression levels of its
      associated GABAB and M1 receptors, respectively. Our results provide evidence
      that Abeta can modulate the expression of these channels which could affect the
      hippocampal activity balance underlying learning and memory processes impaired in
      AD. 

PMID- 26218290
TI  - The effects of spatial frequency on the accommodation responses of myopes and
      emmetropes under various detection demands.
AB  - The dependence of spatial frequency on accommodation has been investigated
      extensively. Recently, differences between myopes and emmetropes with respect to
      accommodative microfluctuations for high spatial frequency targets have been
      reported. Considering the diversity of accommodative responses (ARs) to
      sinusoidal gratings among subjects, this experiment was designed to analyze the
      contrast dependence of ARs to targets with various spatial frequencies (SFs).
      Here, we continuously measured ARs, microfluctuations, and pupil diameter while
      emmetropic and myopic adult subjects fixated on sinusoidal grating targets of
      various SFs under standard and near-detection threshold contrast conditions. We
      first evaluated the detection contrast thresholds at six SFs (2-16 cpd) using a
      near-contrast sensitivity function test that simulated the CSV-1000 test with a
      tablet computer. We found no difference in contrast threshold between emmetropes
      and myopes. We then measured the dynamic ARs to 24 grating targets: six SFs and
      four contrasts (standard, detection threshold, subthreshold and suprathreshold)
      were recorded for 30s. Under standard contrast conditions, we observed a decrease
      in AR with increasing spatial frequency. Variations in pupil diameter and
      accommodation were the smallest at 6 cpd. Both the ARs and microfluctuations were
      higher under near-threshold contrast conditions than under standard contrast
      conditions, and no variations were found across SFs under near-threshold contrast
      conditions. No differences in ARs or microfluctuations were found between the two
      refractive groups at any spatial frequency. These findings provided detailed
      information on accommodative behavior to spatial frequency targets under normal
      and high-detection demand conditions.

PMID- 26218291
TI  - Comparison of Overall Resource Consumption of Biosolids Management System
      Processes Using Exergetic Life Cycle Assessment.
AB  - This study focused on the evaluation of biosolids management systems (BMS) from a
      natural resource consumption point of view. Additionally, the environmental
      impact of the facilities was benchmarked using Life Cycle Assessment (LCA) to
      provide a comprehensive assessment. This is the first study to apply a Cumulative
      Exergy Extraction from the Natural Environment (CEENE) method for an in-depth
      resource use assessment of BMS where two full-scale BMS and seven system
      variations were analyzed. CEENE allows better system evaluation and understanding
      of how much benefit is achievable from the products generated by BMS, which have
      valorization potential. LCA results showed that environmental burden is mostly
      from the intense electricity consumption. The CEENE analysis further revealed
      that the environmental burden is due to the high consumption of fossil and
      nuclear-based natural resources. Using Cumulative Degree of Perfection, higher
      resource-use efficiency, 53%, was observed in the PTA-2 where alkaline
      stabilization rather than anaerobic digestion is employed. However, an anaerobic
      digestion process is favorable over alkaline stabilization, with 35% lower
      overall natural resource use. The most significant reduction of the resource
      footprint occurred when the output biogas was valorized in a combined heat and
      power system.

PMID- 26218292
TI  - Food insecurity, socio-economic factors and weight status in two Iranian ethnic
      groups.
AB  - OBJECTIVE: To study the association of weight status with food insecurity (FI)
      and socio-economic status (SES) in Azeri and Kurd ethnic groups living in Urmia
      city, North-Western Iran. DESIGN: In this cross-sectional study, 723 participants
      (427 women and 296 men) aged 20-64 years old, from two ethnic groups (445 Azeri
      and 278 Kurd), were selected through a combination of cluster, random and
      systematic sampling methods. Demographic and socio-economic characteristics were
      assessed by a valid questionnaire, and household food security status was
      analyzed using an adapted household food insecurity access scale through face-to
      face interviews at homes. General and central obesities were measured and
      evaluated using standard methods. RESULTS: Based on the findings, moderate-to
      severe FI, as well as low SES, was more dominant in Kurds, compared to Azeris.
      After adjusting for confounders, being female (OR = 4.33, CI 95%: 2.35-7.97) and
      moderate-to-severe FI (OR = 2.00, CI 95%: 1.01-3.97) in Azeris and being female
      (OR = 5.39, CI 95%: 2.28-12.23) and higher total cost of household/capita (OR =
      1.005, CI 95%: 1.002-1.009) in Kurds were related to higher odds of general
      obesity while low (OR = 0.41, CI 95%: 0.18-0.91) and moderate (OR = 0.13, CI 95%:
      0.02-0.60) education levels were linked to lower chance of general obesity.
      Furthermore, the chance of central obesity was lower in Azeris with high
      educational levels (OR = 0.64, CI 95%: 0.21-0.94), females (OR = 0.72, CI 95%:
      0.34-0.86), home owners (OR = 0.56, CI 95%: 0.31-0.91) and females Kurds (OR =
      0.60, CI 95%: 0.37-0.97) with moderate-to-severe FI and higher total income per
      capita. In contrast, the chance of central obesity increased in Kurds with
      increased age (OR = 1.06, CI 95%: 1.02-1.10) and total cost of household per
      capita (OR = 1.004, CI 95%: 1.000-1.008). CONCLUSION: These findings show that
      the association between moderate-to-severe FI and risk of general/central obesity
      varies in Azeris, compared to Kurds. However, better SES decreased the chance of
      general/central obesity in both ethnic groups.

PMID- 26218293
TI  - Impaired synaptic development in a maternal immune activation mouse model of
      neurodevelopmental disorders.
AB  - Both genetic and environmental factors are thought to contribute to
      neurodevelopmental and neuropsychiatric disorders with maternal immune activation
      (MIA) being a risk factor for both autism spectrum disorders and schizophrenia.
      Although MIA mouse offspring exhibit behavioral impairments, the synaptic
      alterations in vivo that mediate these behaviors are not known. Here we employed
      in vivo multiphoton imaging to determine that in the cortex of young MIA
      offspring there is a reduction in number and turnover rates of dendritic spines,
      sites of majority of excitatory synaptic inputs. Significantly, spine impairments
      persisted into adulthood and correlated with increased repetitive behavior, an
      ASD relevant behavioral phenotype. Structural analysis of synaptic inputs
      revealed a reorganization of presynaptic inputs with a larger proportion of
      spines being contacted by both excitatory and inhibitory presynaptic terminals.
      These structural impairments were accompanied by altered excitatory and
      inhibitory synaptic transmission. Finally, we report that a postnatal treatment
      of MIA offspring with the anti-inflammatory drug ibudilast, prevented both
      synaptic and behavioral impairments. Our results suggest that a possible altered
      inflammatory state associated with maternal immune activation results in impaired
      synaptic development that persists into adulthood but which can be prevented with
      early anti-inflammatory treatment. 

PMID- 26218296
TI  - Immunity and immune modulation elicited by the larval cestode Mesocestoides vogae
      and its products.
AB  - Larval cestodes (metacestodes) induce long-lasting infections leading to
      considerable pathology in humans and livestock. Their survival is typically
      associated with Th2-biased immune responses and immunosuppressive effects and
      depends on the parasite's ability to excrete/secrete antigens with
      immunoregulatory properties. Here, Mesocestoides vogae, a natural parasite of
      mice, is proposed as a new model species for the identification and
      characterization of cestode-derived immunomodulatory factors. We followed the
      kinetics of immune parameters after infection with M. vogae or exposure to their
      excretory/secretory (ES) products in a permissive strain of mice. Besides, a
      dominant IL-10 production and accumulation of macrophages and eosinophils
      expressing mRNA for Fizz-1, YM1 and Arg-1, mice showed minimal IFN-gamma and
      transient IL-4 production at early time points with a complete loss at later
      stages of infection. We found that serum-free ES products without host
      contamination directly induced M2 macrophages and suppressed IFN-gamma production
      in vivo and in vitro. This study highlights the use of the M. vogae as a cestode
      infection model and its ES products as a valuable tool for the identification of
      new therapeutic targets for the control of larval cestodiasis.

PMID- 26218295
TI  - Dendritic Polyglycerol Sulfate Inhibits Microglial Activation and Reduces
      Hippocampal CA1 Dendritic Spine Morphology Deficits.
AB  - Hyperactivity of microglia and loss of functional circuitry is a common feature
      of many neurological disorders including those induced or exacerbated by
      inflammation. Herein, we investigate the response of microglia and changes in
      hippocampal dendritic postsynaptic spines by dendritic polyglycerol sulfate
      (dPGS) treatment. Mouse microglia and organotypic hippocampal slices were exposed
      to dPGS and an inflammogen (lipopolysaccharides). Measurements of intracellular
      fluorescence and confocal microscopic analyses revealed that dPGS is avidly
      internalized by microglia but not CA1 pyramidal neurons. Concentration and time
      dependent response studies consistently showed no obvious toxicity of dPGS. The
      adverse effects induced by proinflammogen LPS exposure were reduced and dendritic
      spine morphology was normalized with the addition of dPGS. This was accompanied
      by a significant reduction in nitrite and proinflammatory cytokines (TNF-alpha
      and IL-6) from hyperactive microglia suggesting normalized circuitry function
      with dPGS treatment. Collectively, these results suggest that dPGS acts anti
      inflammatory, inhibits inflammation-induced degenerative changes in microglia
      phenotype and rescues dendritic spine morphology. 

PMID- 26218294
TI  - Sleep fragmentation and sepsis differentially impact blood-brain barrier
      integrity and transport of tumor necrosis factor-alpha in aging.
AB  - The factors by which aging predisposes to critical illness are varied, complex,
      and not well understood. Sepsis is considered a quintessential disease of old age
      because the incidence and mortality of severe sepsis increases in old and the
      oldest old individuals. Aging is associated with dramatic changes in sleep
      quality and quantity and sleep increasingly becomes fragmented with age. In
      healthy adults, sleep disruption induces inflammation. Multiple aspects of aging
      and of sleep dysregulation interact via neuroimmune mechanisms. Tumor necrosis
      factor-alpha (TNF), a cytokine involved in sleep regulation and neuroimmune
      processes, exerts some of its effects on the CNS by crossing the blood-brain
      barrier (BBB). In this study we examined the impact of sepsis, sleep
      fragmentation, and aging on BBB disruption and TNF transport into brain. We used
      the cecal ligation and puncture (CLP) model of sepsis in young and aged mice that
      were either undisturbed or had their sleep disrupted. There was a dichotomous
      effect of sepsis and sleep disruption with age: sepsis disrupted the BBB and
      increased TNF transport in young mice but not in aged mice, whereas sleep
      fragmentation disrupted the BBB and increased TNF transport in aged mice, but not
      in young mice. Combining sleep fragmentation and CLP did not produce a greater
      effect on either of these BBB parameters than did either of these manipulations
      alone. These results suggest that the mechanisms by which sleep fragmentation and
      sepsis alter BBB functions are fundamentally different from one another and that
      a major change in the organism's responses to those insults occurs with aging. 

PMID- 26218297
TI  - One-step DGC assembly and structural characterization of a hairy particle zeolite
      like organic-inorganic hybrid as an efficient modifiable catalytic material.
AB  - Organic-inorganic hybrid microporous crystalline molecular sieves, extending the
      application of conventional zeolites in the fields of selective catalysis and
      adsorption, have aroused great interest in chemists. However, the complicated and
      difficult synthesis of organic-inorganic hybrid microporous molecular sieves by
      using a conventional hydrothermal method has hindered the rapid development of
      this field. The present work describes the recent progress in the synthesis of a
      hairy particle zeolite-like organic-inorganic hybrid with the high organic group
      content by one-step dry-gel conversion (DGC) assembly of organic Si, inorganic Si
      and other inorganic species without any organic template, which is proven to be
      efficient, economical, simple, and controllable. Thus-synthesized hybrid
      materials, as we know, with the highest organic group content reported in the
      literature, can be bestowed with modifiable catalytic activities by different
      treatments. This study will be applicable for the development of organic
      inorganic hybrid catalytic materials. 

PMID- 26218298
TI  - Correction of the FSHD myoblast differentiation defect by fusion with healthy
      myoblasts.
AB  - Facioscapulohumeral dystrophy (FSHD) is a neuromuscular disease with a prevalence
      that could reach 1 in 8,000 characterized by progressive asymmetric muscle
      weakness. Myoblasts isolated from FSHD muscles exhibit morphological
      differentiation defects and show a distinct transcription profile. These
      abnormalities may be linked to the muscle weakness in FSHD patients. We have
      tested whether fusion of FSHD myoblasts with primary myoblasts isolated from
      healthy individuals could correct the differentiation defects. Our results show
      that the number of hybrid myotubes with normal phenotype increased with the
      percentage of normal myoblasts initially cultured. We demonstrated that a minimum
      of 50% of normal nuclei is required for a phenotypic correction of the FSHD
      phenotype. Moreover, transcriptomic profiles of phenotypically corrected hybrid
      myotubes showed that the expression of deregulated genes in FSHD myotubes became
      almost normal. The number of deregulated pathways also decreased from 39 in FSHD
      myotubes to one in hybrid myotubes formed with 40% FSHD and 60% normal myoblasts.
      We thus propose that while phenotypical and functional correction of FSHD is
      feasible, it requires more than 50% of normal myoblasts, it creates limitations
      for cell therapy in the FSHD context.

PMID- 26218300
TI  - Highly efficient micellar extraction of toxic picric acid into novel ionic
      liquid: Effect of parameters, solubilization isotherm, evaluation of
      thermodynamics and design parameters.
AB  - A simple and new approach in cloud point extraction (CPE) method was developed
      for removal of picric acid (PA) by the addition of N,N,N,N',N',N'-hexaethyl
      ethane-1,2-diammonium dibromide ionic liquid (IL) in non-ionic surfactant Triton
      X-114 (TX-114). A significant increase in extraction efficiency was found upon
      the addition of dicationic ionic liquid (DIL) at both nearly neutral and high
      acidic pH. The effects of different operating parameters such as pH, temperature,
      time, concentration of surfactant, PA and DIL on extraction of PA were
      investigated and optimum conditions were established. The extraction mechanism
      was also proposed. A developed Langmuir isotherm was used to compute the feed
      surfactant concentration required for the removal of PA up to an extraction
      efficiency of 90%. The effects of temperature and concentration of surfactant on
      various thermodynamic parameters were examined. It was found that the values of
      DeltaG degrees  increased with temperature and decreased with surfactant
      concentration. The values of DeltaH degrees  and DeltaS degrees  increased with
      surfactant concentration. The developed approach for DIL mediated CPE has proved
      to be an efficient and green route for extraction of PA from water sample. 

PMID- 26218299
TI  - Clinical and pathological features of Burkitt lymphoma showing expression of BCL2
      -an analysis including gene expression in formalin-fixed paraffin-embedded
      tissue.
AB  - The differential diagnosis between Burkitt lymphoma (BL) and diffuse large B-cell
      lymphoma (DLBCL) can be challenging. BL has been reported to express less BCL2
      than DLBCL, but this issue has not been analysed systematically. BL expressing
      BCL2 can be considered to be MYC/BCL2 co-expressors, a feature that is associated
      with poorer outcome in DLBCL but that has not been correlated with outcome in BL
      so far. We analysed the expression of BCL2 in 150 cases of conventionally
      diagnosed BL using two different BCL2 antibodies. BCL2 expression was detected in
      23% of the cases, though the expression varied in intensity and number of
      positive cells. We did not detect any relevant differences in clinical
      presentation and outcome between BCL2-positive and BCL2-negative BL in a subgroup
      of 43 cases for which detailed clinical data were available. An independent
      cohort of 17 BL with expression of BCL2 were analysed molecularly, with 13 of 17
      cases classified as molecularly defined BL (Burkitt Lymphoma) using gene
      expression profiling on formalin-fixed paraffin-embedded tissues. The four
      lymphomas diagnosed molecularly as intermediates did not differ in clinical
      presentation and outcome from molecularly defined BL. 

PMID- 26218301
TI  - Photocatalytic degradation of eleven microcystin variants and nodularin by TiO2
      coated glass microspheres.
AB  - Microcystins and nodularin are toxic cyanobacterial secondary metabolites
      produced by cyanobacteria that pose a threat to human health in drinking water.
      Conventional water treatment methods often fail to remove these toxins. Advanced
      oxidation processes such as TiO2 photocatalysis have been shown to effectively
      degrade these compounds. A particular issue that has limited the widespread
      application of TiO2 photocatalysis for water treatment has been the separation of
      the nanoparticulate powder from the treated water. A novel catalyst format, TiO2
      coated hollow glass spheres (PhotospheresTM), is far more easily separated from
      treated water due to its buoyancy. This paper reports the photocatalytic
      degradation of eleven microcystin variants and nodularin in water using
      PhotospheresTM. It was found that the PhotospheresTM successfully decomposed all
      compounds in 5 min or less. This was found to be comparable to the rate of
      degradation observed using a Degussa P25 material, which has been previously
      reported to be the most efficient TiO2 for photocatalytic degradation of
      microcystins in water. Furthermore, it was observed that the degree of initial
      catalyst adsorption of the cyanotoxins depended on the amino acid in the variable
      positions of the microcystin molecule. The fastest degradation (2 min) was
      observed for the hydrophobic variants (microcystin-LY, -LW, -LF). Suitability of
      UV-LEDs as an alternative low energy light source was also evaluated.

PMID- 26218302
TI  - Insights into the photochemical transformation pathways of triclosan and 2'-HO
      BDE-28.
AB  - Hydroxylated polyhalogenated diphenyl ethers (HO-PXDEs) have been recognized as a
      group of widely detected emerging contaminants in natural waters. Photolysis was
      proved to be an important transformation pathway for these compounds and their
      direct phototransformation results in highly toxic dioxins. However, the roles of
      excited states and reactive oxygen species in the photochemical transformation of
      these compounds are still unclear. In this study, 2'-HO-2,4,4'-trichlorodiphenyl
      ether (triclosan) and 2'-HO-2,4,4'-tribromodiphenyl ether (2'-HO-BDE-28) were
      selected as model compounds to investigate their phototransformation processes.
      Results showed that the direct photolysis reactions of both triclosan and 2'-HO
      BDE-28 occurred via their respective excited singlet states, leading to the
      generation of dioxins. In addition, the energy and electron transfer reactions
      between excited states of model compounds and molecular O2 can lead to the
      generation of (1)O2 and OH, which results in self-sensitized photolysis. We also
      found that both the k, Phi dioxin yield for anionic triclosan were higher than
      those of anionic 2'-HO-BDE-28. This study revealed the roles of the excited
      states in direct photolysis and the generation pathway of reactive oxygen species
      in self-sensitized photolysis of HO-PXDEs, which is important for understanding
      the phototransformation mechanisms of HO-PXDEs. 

PMID- 26218303
TI  - Global styrene oligomers monitoring as new chemical contamination from
      polystyrene plastic marine pollution.
AB  - Polystyrene (PS) plastic marine pollution is an environmental concern. However, a
      reliable and objective assessment of the scope of this problem, which can lead to
      persistent organic contaminants, has yet to be performed. Here, we show that
      anthropogenic styrene oligomers (SOs), a possible indicator of PS pollution in
      the ocean, are found globally at concentrations that are higher than those
      expected based on the stability of PS. SOs appear to persist to varying degrees
      in the seawater and sand samples collected from beaches around the world. The
      most persistent forms are styrene monomer, styrene dimer, and styrene trimer.
      Sand samples from beaches, which are commonly recreation sites, are particularly
      polluted with these high SOs concentrations. This finding is of interest from
      both scientific and public perspectives because SOs may pose potential long-term
      risks to the environment in combination with other endocrine disrupting
      chemicals. From SOs monitoring results, this study proposes a flow diagram for
      SOs leaching from PS cycle. Using this flow diagram, we conclude that SOs are
      global contaminants in sandy beaches around the world due to their broad spatial
      distribution. 

PMID- 26218304
TI  - Three novel triazine-based materials with different O/S/N set of donor atoms: One
      step preparation and comparison of their capability in selective separation of
      uranium.
AB  - Cyanuric chloride was chosen as a core skeleton which reacted with desired linker
      molecules, urea, thiourea and thiosemicarbazide, to prepare three novel
      functional covalent triazine-based frameworks, CCU (O-donor set), CCTU (S-donor
      set) and CCTS (S, N-donor set) respectively, designed for selective adsorption of
      U(VI). The products have high nitrogen concentration (>30 wt%), regular
      structure, relatively high chemical and thermal stability. Adsorption behaviors
      of the products on U(VI) were examined by batch experiments. CCU and CCTU can
      extract U(VI) from simulated nuclear industrial effluent containing 12 co
      existing cations with relatively high selectivity (54.4% and 54.2%,
      respectively). Especially, effects of donor atoms O/S on adsorption were
      investigated, and the outcomes indicate that the difference in coordinating
      ability between the donor atoms is weakened in large conjugated systems, and the
      related functional groups with originally very strong coordination abilities may
      not be the best choice for the application in selective adsorption of uranium and
      also other metals. The as-proposed approach can easily be expanded into design
      and preparation of new highly efficient adsorbents for selective separation and
      recovery of uranium through adjusting the structures, types and amounts of
      functional groups of adsorbents by choosing suitable linkers.

PMID- 26218305
TI  - Evaluating the efficiency of an asbestos stabilizer on ceiling tiles and the
      characteristics of the released asbestos fibers.
AB  - The efficiency of asbestos stabilizers and their adaptability were evaluated by
      investigating the characteristics of asbestos fibers released from ceiling tiles.
      The impact of such variables as the wind speed or vibration conditions was also
      studied along with the asbestos stabilizers. The concentrations of the asbestos
      fibers released from damaged ceiling tiles treated with stabilizers decreased by
      69.5-84.4% compared with those of untreated tiles for all variables, with a
      statistically significant difference (p<0.001). The effects of the environmental
      factors on the asbestos concentrations were analyzed through a multiple
      regression analysis. It was determined that the surface status of the ceiling
      tiles and stabilizers were the main factors affecting the concentration, and the
      reliability of these factors was estimated as 58.3%. The lengths of the
      chrysotile fibers released from the damaged ceiling tiles were in the range of
      0.991-79.1 MUm for the untreated tiles and 3.74-35.6 MUm for the tiles treated
      with inorganic stabilizers. It was confirmed that inorganic stabilizers are more
      efficient for damaged ceiling tiles. The results of this study also show that the
      asbestos concentrations are greatly reduced after treating damaged ceiling tiles
      with a stabilizer.

PMID- 26218307
TI  - Heart beat detection in multimodal data using automatic relevant signal
      detection.
AB  - Accurate R peak detection in the electrocardiogram (ECG) is a well-known and
      highly explored problem in biomedical signal processing. Although a lot of
      progress has been made in this area, current methods are still insufficient in
      the presence of extreme noise and/or artifacts such as loose electrodes. Often,
      however, not only the ECG is recorded, but multiple signals are simultaneously
      acquired from the patient. Several of these signals, such as blood pressure, can
      help to improve the heart beat detection. These signals of interest can be
      detected automatically by analyzing their power spectral density or by using the
      available signal type identifiers. Individual peaks from the signals of interest
      are combined using majority voting, heart beat location estimation and Hjorth's
      mobility of the resulting RR intervals. Both multimodal algorithms showed
      significant increases in performance of up to 8.65% for noisy multimodal datasets
      compared to when only the ECG signal is used. A maximal performance of 90.02% was
      obtained on the hidden test set of the Physionet/Computing in Cardiology
      Challenge 2014: Robust Detection of Heart Beats in Multimodal Data. 

PMID- 26218306
TI  - Removal of caffeine from aqueous solution by indirect electrochemical oxidation
      using a graphite-PVC composite electrode: A role of hypochlorite ion as an
      oxidising agent.
AB  - The electrochemical oxidation of caffeine, a widely over-the-counter stimulant
      drug, has been investigated in effluent wastewater and deionized water (DIW)
      using graphite-poly vinyl chloride (PVC) composite electrode as anode. Effects of
      initial concentration of caffeine, chloride ion (Cl(-)) loading, presence of
      hydrogen peroxide (H2O2), sample volume, type of sample and applied voltage were
      determined to test and to validate a kinetic model for the oxidation of caffeine
      by the electrochemical oxidation process. The results revealed that the
      electrochemical oxidation rates of caffeine followed pseudo first-order kinetics,
      with rate constant values ranged from 0.006 to 0.23 min(-1) depending on the
      operating parameters. The removal efficiency of caffeine increases with applied
      voltage very significantly, suggesting a very important role of mediated
      oxidation process. However, the consumption energy was considered during
      electrochemical oxidation process. In chloride media, removal of caffeine is
      faster and more efficiently, although occurrence of more intermediates takes
      place. The study found that the adding H2O2 to the NaCl solution will inhibit
      slightly the electrochemical oxidation rate in comparison with only NaCl in
      solution. Liquid chromatography-time of flight-mass spectrometry (LC-TOF-MS)
      technique was applied to the identification of the by-products generated during
      electrochemical oxidation, which allowed to construct the proposed structure of
      by-products.

PMID- 26218309
TI  - Ischemic Preconditioning and Exercise Performance: A Systematic Review and Meta
      Analysis.
AB  - Although the amount of evidence demonstrating the beneficial effects of ischemic
      preconditioning (IPC) on exercise performance is increasing, conclusions about
      its efficacy cannot yet be drawn. Therefore, the purposes of this review were to
      determine the effect of IPC on exercise performance and identify the effects of
      different IPC procedures, exercise types, and subject characteristics on exercise
      performance. The analysis comprised 19 relevant studies from 2000 to 2015, 15 of
      which were included in the meta-analyses. Effect sizes (ES) were calculated as
      the standardized mean difference. Overall, IPC had a small beneficial effect on
      exercise performance (ES = 0.43; 90% confidence interval [CI], 0.28 to 0.51). The
      largest ES were found for aerobic (ES = 0.51; 90% CI, 0.35 to 0.67) and anaerobic
      (ES = 0.23; 90% CI, -0.12 to 0.58) exercise. In contrast, an unclear effect was
      observed in power and sprint performance (ES = 0.16; 90% CI, -0.20 to 0.52). In
      conclusion, IPC can effectively enhance aerobic and anaerobic exercise
      performance. 

PMID- 26218308
TI  - A complete mitochondrial DNA genome derived from a Chinese population of the
      Bemisia afer species complex (Hemiptera: Aleyrodidae).
AB  - We report here the sequence of a complete mitochondrial genome (mitogenome) of a
      population of Bemisia afer species complex, which was collected from
      Abutilonaviecnnae gaerner at LinYi, Shan Dong province of China (hereafter B.
      afer_China_Ag) (GenBank accession number: KR819174). The mitogenome of B.
      afer_China_Ag is 15 300 bp and contains 13 protein-coding genes, 22 transfer
      RNAs, 2 ribosomal RNAs, and 2 control regions. The content and arrangement of
      mitochondrial genes of B. afer_China_Ag exhibit remarkable differences from the
      mitogenome of a B. afer population collected from African cassava (KF734668).
      Phylogenetic analyses based on 13 protein-coding genes support the close
      relationship of the two sequenced B. afer mitogenomes and confirm the species
      status of our specimen.

PMID- 26218313
TI  - CCN2 and CCN5 exerts opposing effect on fibroblast proliferation and
      transdifferentiation induced by TGF-beta.
AB  - Epidural fibrosis might occur after lumbar discectomy and contributes to failed
      back syndrome. Transforming growth factor (TGF)-beta has been reported to
      influence multiple organ fibrosis, in which connective tissue growth
      factor/cysteine-rich 61/nephroblastoma overexpressed 2 (CCN2) and CCN5 are
      involved. However, the effect of CCN2 and CCN5 on TGF-beta induced fibrosis has
      not yet been elucidated. This study reports that CCN2 and CCN5 play opposing
      roles in cell proliferation and transdifferentiation of human skin fibroblasts or
      rabbit epidural scar-derived fibroblasts exposed to TGF-beta. We observed that
      TGF-beta1 induced fibroblasts proliferation and differentiation in a dose
      dependent manner (from 0 MUg/L to 20 MUg/L). Meanwhile, CCN2 expression is up
      regulated while CCN5 expression is inhibited by TGF-beta1 exposure. Furthermore,
      it is demonstrated that CCN2 overexpression leads to promoted proliferation and
      elevated collagen and alpha-smooth muscle actin (alpha-SMA) expression, which are
      inhibited by CCN5 overexpression. Moreover, it is shown that the cysteine knot
      (CT) domain, present in CCN2 but absent in CCN5, plays an essential part in
      fibroblast proliferation and differentiation. Additionally, enhanced TGF-beta and
      CCN2 expression but decreased CCN5 expression is found in rabbit epidural scar
      derived fibroblasts. Overall, the results show the opposing effects of CCN2 and
      CCN5 on fibroblast proliferation and transdifferentiation induced by TGF-beta. 

PMID- 26218314
TI  - Expression and clinical implication of cyclooxygenase-2 and e-cadherin in oral
      squamous cell carcinomas.
AB  - Epithelial-Mesenchymal Transition (EMT) and angiogenesis are crucial events for
      development of aggressive and often fatal Oral Squamous Cell Carcinomas (OSCCs).
      Both promote cancer progression and metastasis development, but while the former
      induces the loss of E-cadherin expression and, hence cadherin switching; the
      latter produces haematic blood vessel neo-formation and contribute to OSCC cell
      growth, tumor mass development, and dissemination. Cyclooxygenase-2 (COX-2) has
      an important role, not only in angiogenic mechanisms, but also in favoring cancer
      invasion. Indeed it decreases the expression of E-cadherin and leads to
      phenotypic changes in epithelial cells (EMT) enhancing their carcinogenic
      potential. Our aim is to evaluate the interplay between E-cadherin cytoplasmic
      delocalization, COX-2 up-regulation and COX-2 induced neo-angiogenesis in 120
      cases of OSCC. We have analyzed the distribution and the number of neo-formed
      endothelial buds surrounding infiltrating cells that express COX-2, as well as
      the neo-formed vessels in chronic inflammatory infiltrate, which surround the
      tumor. A double immunostaining method was employed in order to verify co
      localization of endothelial cell marker (CD34) and COX-2. IHC has also been used
      to assess E-cadherin expression. Our data demonstrate that the OSCC cells, which
      lose membranous E-cadherin staining, acquiring a cytoplasmic delocalization,
      overexpress COX-2. Moreover, we find a new CD34+ vessel formation (sprouting
      angiogenesis). Only basaloid type of OSCC showes low level of COX-2 expression
      together with very low level of neo-angiogenesis and consequent tumor necrosis.
      The well-known anti-metastatic effect of certain COX-2 inhibitors suggests that
      these molecules might have clinical utility in the management of advanced
      cancers.

PMID- 26218315
TI  - Real-time PCR to supplement gold-standard culture-based detection of Legionella
      in environmental samples.
AB  - AIMS: Culture remains the gold-standard for the enumeration of environmental
      Legionella. However, it has several drawbacks including long incubation and poor
      sensitivity, causing delays in response times to outbreaks of Legionnaires'
      disease. This study aimed to validate real-time PCR assays to quantify Legionella
      species (ssrA gene), Legionella pneumophila (mip gene) and Leg. pneumophila
      serogroup-1 (wzm gene) to support culture-based detection in a frontline public
      health laboratory. METHODS AND RESULTS: Each qPCR assay had 100% specificity,
      excellent sensitivity (5 GU/reaction) and reproducibility. Comparison of the
      assays to culture-based enumeration of Legionella from 200 environmental samples
      showed that they had a negative predictive value of 100%. Thirty eight samples
      were positive for Legionella species by culture and qPCR. One hundred samples
      were negative by both methods, whereas 62 samples were negative by culture but
      positive by qPCR. The average log10 increase between culture and qPCR for
      Legionella spp. and Leg. pneumophila was 0.72 (P = 0.0002) and 0.51 (P = 0.006),
      respectively. CONCLUSIONS: The qPCR assays can be conducted on the same 1 l water
      sample as culture thus can be used as a supplementary technique to screen out
      negative samples and allow more rapid indication of positive samples.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The assay could prove informative in public
      health investigations to identify or rule out sources of Legionella as well as to
      specifically identify Leg. pneumophila serogroup 1 in a timely manner not
      possible with culture.

PMID- 26218317
TI  - Myelination: actin disassembly leads the way.
AB  - The mechanisms that drive the spiral wrapping of the myelin sheath around axons
      are poorly understood. Two papers in this issue of Developmental Cell demonstrate
      that actin disassembly, rather than actin assembly, predominates during
      oligodendrocyte maturation and is critical for the genesis of the central myelin
      sheath. 

PMID- 26218316
TI  - The molecules that mediate sensory transduction in the mammalian inner ear.
AB  - Years of searching and researching have finally yielded a few leads in the quest
      to identify molecules required for mechanosensory transduction in the mammalian
      inner ear. Studies of human and mouse genetics have raised the profile of several
      molecules that are crucial for the function sensory hair cells. Follow up studies
      have begun to define the molecular function and biochemical interactions of
      several key proteins. These studies have exposed a sensory transduction apparatus
      that is more complex than originally envisioned and have reinvigorated the search
      for additional molecular components required for normal inner ear function. 

PMID- 26218318
TI  - Where steroids meet the cell cycle in architecture.
AB  - Understanding how plant architecture is controlled is not only important from a
      developmental point of view, but it also has direct consequence for agriculture.
      Reporting in this issue of Developmental Cell, Sun et al. (2015) unravel a
      cascade from Brassinosteroids to a poorly understood U-type cyclin in rice leaf
      erectness. 

PMID- 26218319
TI  - Regulated degradation: controlling the stability of autophagy gene transcripts.
AB  - Autophagy is involved in diverse cellular functions through degradation of
      various intracellular constituents, and hence must be tightly controlled. A
      recent study by Hu et al. (2015) in Nature Cell Biology adds a new layer of
      autophagy regulation, involving Tor kinase-driven degradation of mRNAs encoding
      autophagy-related proteins. 

PMID- 26218320
TI  - Neutrophils, wounds, and cancer progression.
AB  - Chronic inflammation is associated with tumorigenesis, but how acute inflammation
      affects the tumor microenvironment is less known. Recently, Antonio et al. (2015)
      found that neutrophils attracted to an acute wound such as a biopsy drive cell
      proliferation of nearby pre-neoplastic cells, suggesting that acute wounds may
      promote cancer progression. 

PMID- 26218321
TI  - Embryos, camera, laser, action!
AB  - The Arabidopsis embryo establishes polarity and main tissue types with the first
      five rounds of cell division. In this issue of Developmental Cell, Gooh et al.
      (2015) provide tools toward elucidating this poorly understood process through
      the first movies and targeted manipulations of early embryos developing inside
      cultured seeds. 

PMID- 26218322
TI  - Room-Temperature, Strain-Tunable Orientation of Magnetization in a Hybrid
      Ferromagnetic Co Nanorod-Liquid Crystalline Elastomer Nanocomposite.
AB  - Hybrid nanocomposites based on magnetic nanoparticles dispersed in liquid
      crystalline elastomers are fascinating emerging materials. Their expected strong
      magneto-elastic coupling may open new applications as actuators, magnetic
      switches, and for reversible storage of magnetic information. We report here the
      synthesis of a novel hybrid ferromagnetic liquid crystalline elastomer. In this
      material, highly anisotropic Co nanorods are aligned through a cross-linking
      process performed in the presence of an external magnetic field. We obtain a
      highly anisotropic magnetic material which exhibits remarkable magneto-elastic
      coupling. The nanorod alignment can be switched at will at room temperature by
      weak mechanical stress, leading to a change of more than 50 % of the remnant
      magnetization ratio and of the coercive field. 

PMID- 26218323
TI  - Adsorption and desorption kinetics of (60)Co and (137)Cs in fresh water rivers.
AB  - Radionuclides released in water systems--as well as heavy metals and organic
      toxicants--sorb to both the suspended solid particles and the bed sediments.
      Sorption is usually represented mathematically by the distribution coefficient.
      This approach implies equilibrium between phases and instantaneous fixation
      (release) of the pollutant onto (from) the surface of the soil particle. However,
      empirical evidence suggests that for some radionuclides the fixation is not
      achieved instantaneously and that the reversibility of the process can be slow.
      Here the adsorption/desorption kinetics of (60)Co and (137)Cs in fresh water
      environments were simulated experimentally and later on modelled mathematically,
      while the influence of the most relevant factors affecting the sorption were
      taken into account. The experimental results suggest that for adsorption and the
      desorption more than 24 h are needed to reach equilibrium, moreover, It was
      observed that the desorption rate constants for (60)Co and (137)Cs lie within
      ranges which are of two to three orders of magnitude lower than the adsorption
      rate constants.

PMID- 26218324
TI  - Investigations into the Kinetic Modeling of the Direct Alkylation of Benzylic
      Amines: Dissolution of K2CO3 Is Responsible for the Observation of an Induction
      Period.
AB  - Investigations into the kinetics of a Rh(I)-catalyzed direct C-H alkylation of
      benzylic amines with alkenes revealed that K2CO3, which is effectively insoluble
      in the reaction mixture, is only needed in the beginning of the reaction. During
      the concomitant induction period, K2CO3 is proposed to dissolve to a vanishingly
      small extent and the Rh-precatalyst irreversibly reacts with dissolved K2CO3 to
      form the active catalyst. The duration of this induction period is dependent on
      the molar loading, the specific surface, the H2O content of K2CO3, and agitation,
      and these dependences can be rationalized based on a detailed kinetic model. 

PMID- 26218325
TI  - Dynamic Responses and Initial Decomposition under Shock Loading: A DFTB
      Calculation Combined with MSST Method for beta-HMX with Molecular Vacancy.
AB  - Despite extensive efforts on studying the decomposition mechanism of HMX under
      extreme condition, an intrinsic understanding of mechanical and chemical response
      processes, inducing the initial chemical reaction, is not yet achieved. In this
      work, the microscopic dynamic response and initial decomposition of beta-HMX with
      (1 0 0) surface and molecular vacancy under shock condition, were explored by
      means of the self-consistent-charge density-functional tight-binding method (SCC
      DFTB) in conjunction with multiscale shock technique (MSST). The evolutions of
      various bond lengths and charge transfers were analyzed to explore and understand
      the initial reaction mechanism of HMX. Our results discovered that the C-N bond
      close to major axes had less compression sensitivity and higher stretch activity.
      The charge was transferred mainly from the N-NO2 group along the minor axes and H
      atom to C atom during the early compression process. The first reaction of HMX
      primarily initiated with the fission of the molecular ring at the site of the C-N
      bond close to major axes. Further breaking of the molecular ring enhanced
      intermolecular interactions and promoted the cleavage of C-H and N-NO2 bonds.
      More significantly, the dynamic response behavior clearly depended on the angle
      between chemical bond and shock direction. 

PMID- 26218326
TI  - Causal mechanisms of mirror-touch synesthesia: Clues from neuropsychology.
AB  - Ward and Banissy offer a critical discussion of Mirror-Touch Synesthesia (MTS),
      with reference to Threshold and Self-Other theories. The authors argue that
      developmental MTS is linked to differences in the functioning of a mirror system
      for touch (and pain), which are driven by neurocognitive alterations that lie
      outside of the somatosensory system and concern bodily awareness and/or the
      control of self-other representations. This commentary briefly presents some
      neuropsychological evidence in line with Ward and Banissy's argument, questioning
      the potential similarities between MTS and some post-stroke disorders of body
      representation. 

PMID- 26218327
TI  - Steep Subthreshold Swing n- and p-Channel Operation of Bendable Feedback Field
      Effect Transistors with p(+)-i-n(+) Nanowires by Dual-Top-Gate Voltage
      Modulation.
AB  - In this study, we present the steep switching characteristics of bendable
      feedback field-effect transistors (FBFETs) consisting of p(+)-i-n(+) Si nanowires
      (NWs) and dual-top-gate structures. As a result of a positive feedback loop in
      the intrinsic channel region, our FBFET features the outstanding switching
      characteristics of an on/off current ratio of approximately 10(6), and point
      subthreshold swings (SSs) of 18-19 mV/dec in the n-channel operation mode and of
      10-23 mV/dec in the p-channel operation mode. Not only can these devices operate
      in n- or p-channel modes, their switching characteristics can also be modulated
      by adjusting the gate biases. Moreover, the device maintains its steep SS
      characteristics, even when the substrate is bent. This study demonstrates the
      promising potential of bendable NW FBFETs for use as low-power components in
      integrated circuits or memory devices. 

PMID- 26218329
TI  - The limits of passive motion are variable between and unrelated within normal
      tibiofemoral joints.
AB  - Patient-to-patient differences should be accounted for in both clinical
      evaluations and computational models of knee laxity. Accordingly, the objectives
      were to determine how variable the laxities are between knees by determining the
      range of the internal-external (I-E), varus-valgus (V-V), anterior-posterior (A
      P), and compression-distraction (C-D) limits of passive motion, and how related
      the laxities are within a knee by determining whether these limits are correlated
      with one another. The limits in I-E (+/- 3 Nm), V-V (+/- 5 Nm), A-P (+/- 45 N),
      and C-D (+/- 100 N) were measured in 10 normal human cadaveric knees at 0 degrees
      to 120 degrees  flexion in 15 degrees  increments using a six degree-of-freedom
      load application system. The ranges from 15 degrees  to 120 degrees  flexion of
      the I-E limits were greater than 3.6 degrees , of the A-P limits were greater
      than 1.8 mm, and of the varus limits were greater than 1.4 degrees . The ranges
      from 30 degrees  to 120 degrees  flexion of the distraction limits were greater
      than 2.0 mm. Twenty-four of the 28 pair-wise comparisons between the limits had a
      correlation coefficient less than 0.65. These results demonstrate that a patient
      specific approach, including all degrees of freedom of interest, is necessary
      during clinical evaluations of laxity and when creating and validating
      computational models of the tibiofemoral joint.

PMID- 26218330
TI  - Low expression of chloride channel accessory 1 predicts a poor prognosis in
      colorectal cancer: The question is still open.

PMID- 26218332
TI  - Identifying the cognitive predictors of early counting and calculation skills:
      Evidence from a longitudinal study.
AB  - The extent to which phonological, visual-spatial short-term memory (STM), and
      nonsymbolic quantitative skills support the development of counting and
      calculation skills was examined in this 14-month longitudinal study of 125
      children. Initial assessments were made when the children were 4 years 8 months
      old. Phonological awareness, visual-spatial STM, and nonsymbolic approximate
      discrimination predicted growth in early calculation skills.These results suggest
      that both the approximate number system and domain-general phonological and
      visual-spatial skills support early calculation. In contrast, only performance on
      a small nonsymbolic quantity discrimination task (where the presented quantities
      were always within the subitizing range) predicted growth in cardinal counting
      skills. These results suggest that the development of counting and the
      development of calculation are supported by different cognitive abilities.

PMID- 26218333
TI  - How preschool executive functioning predicts several aspects of math achievement
      in Grades 1 and 3: A longitudinal study.
AB  - This longitudinal study analyzes whether selected components of executive
      function (EF) measured during the preschool period predict several indices of
      math achievement in primary school. Six EF measures were assessed in a sample of
      5-year-old children (N = 175). The math achievement of the same children was then
      tested in Grades 1 and 3 using both a composite math score and three single
      indices of written calculation, arithmetical facts, and problem solving. Using
      previous results obtained from the same sample of children, a confirmatory factor
      analysis examining the latent EF structure in kindergarten indicated that a two
      factor model provided the best fit for the data. In this model, inhibition and
      working memory (WM)-flexibility were separate dimensions. A full structural
      equation model was then used to test the hypothesis that math achievement (the
      composite math score and single math scores) in Grades 1 and 3 could be explained
      by the two EF components comprising the kindergarten model. The results indicate
      that the WM-flexibility component measured during the preschool period
      substantially predicts mathematical achievement, especially in Grade 3. The math
      composite scores were predicted by the WM-flexibility factor at both grade
      levels. In Grade 3, both problem solving and arithmetical facts were predicted by
      the WM-flexibility component. The results empirically support interventions that
      target EF as an important component of early childhood mathematics education.

PMID- 26218331
TI  - TRPM7 and its role in neurodegenerative diseases.
AB  - Calcium (Ca(2+)) and magnesium (Mg(2+)) ions have been shown to play an important
      role in regulating various neuronal functions. In the present review we focus on
      the emerging role of transient potential melastatin-7 (TRPM7) channel in not only
      regulating Ca(2+) and Mg(2+) homeostasis necessary for biological functions, but
      also how alterations in TRPM7 function/expression could induce neurodegeneration.
      Although eight TRPM channels have been identified, the channel properties, mode
      of activation, and physiological responses of various TRPM channels are quite
      distinct. Among the known 8 TRPM channels only TRPM6 and TRPM7 channels are
      highly permeable to both Ca(2+) and Mg(2+); however here we will only focus on
      TRPM7 as unlike TRPM6, TRPM7 channels are abundantly expressed in neuronal cells.
      Importantly, the discrepancy in TRPM7 channel function and expression leads to
      various neuronal diseases such as Alzheimer disease (AD) and Parkinson disease
      (PD). Further, it is emerging as a key factor in anoxic neuronal death and in
      other neurodegenerative disorders. Thus, by understanding the precise involvement
      of the TRPM7 channels in different neurodegenerative diseases and by
      understanding the factors that regulate TRPM7 channels, we could uncover new
      strategies in the future that could evolve as new drug therapeutic targets for
      effective treatment of these neurodegenerative diseases. 

PMID- 26218334
TI  - 75th Birthday of Prof. Dr. rer. nat. Dres. h. c. Adolf Nahrstedt.

PMID- 26218335
TI  - Evaluation of Cytotoxic and Antitumour Properties of Apodytes dimidiata and
      Characterisation of the Bioactive Component.
AB  - Apodytes dimidiata, belonging to the family Icacinaceae, is used for treating
      inflammation and various gastrointestinal ailments in Zulu traditional medicine.
      In the present study, significant cytotoxicity was exhibited by the methanolic
      extract of the A. dimidiata leaf against various cancer cell lines. The extract
      was purified partially through silica gel column by successive elution using
      various solvents of increasing polarity. Among these, the active methanolic
      fraction was found to be the most cytotoxic with IC50 values ranging from 0.92 to
      3.95 ug/mL for Ehrlich's ascites carcinoma (a carcinoma cell line), Jurkat (human
      T lymphocyte cell line), and SK-BR-3 (mammary tumour cell line). The treated
      cells showed morphological alterations characteristic of apoptosis. Upon oral
      administration of active methanolic fraction at a dose of 250 mg/kg body weight,
      the solid tumour volume in mice was significantly reduced to 55.14% and the life
      span of the ascites tumour-bearing mice increased to 44.65% compared to untreated
      control. The active fraction with Rf value 0.56 was purified from the methanolic
      fraction by preparative thin-layer chromatography and was subjected to high
      performance thin-layer chromatography, high-performance liquid chromatography,
      liquid chromatography-mass spectrometry, and nuclear magnetic resonance analysis.
      The iridoid glycoside genipin was identified as the active component.

PMID- 26218336
TI  - Simultaneous Characterization of Intravenous and Oral Pharmacokinetics of
      Lychnopholide in Rats by Transit Compartment Model.
AB  - The pharmacokinetic properties of a new molecular entity are important aspects in
      evaluating the viability of the compound as a pharmacological agent. The
      sesquiterpene lactone lychnopholide exhibits important biological activities. The
      objective of this study was to characterize the pharmacokinetics of lychnopholide
      after intravenous administration of 1.65 mg/kg (n = 5) and oral administration of
      3.3 mg/kg (n = 3) lychnopholide in rats (0.2 +/- 0.02 kg in weight) through
      nonlinear mixed effects modeling and non-compartmental pharmacokinetic analysis.
      A highly sensitive analytical method was used to quantify the plasma
      lychnopholide concentrations in rats. Plasma protein binding of this compound was
      over 99 % as determined by a filtration method. A two-compartment body model plus
      three transit compartments to characterize the absorption process best described
      the disposition of lychnopholide after both routes of administration. The oral
      bioavailability was approximately 68 %. The clearance was 0.131 l/min and
      intercompartmental clearance was 0.171 l/min; steady-state volume of distribution
      was 4.83 l. The mean transit time for the absorption process was 9.15 minutes. No
      flip-flop phenomenon was observed after oral administration. The pharmacokinetic
      properties are favorable for further development of lychnopholide as a potential
      oral pharmacological agent.

PMID- 26218337
TI  - Stryphnodendron adstringens: Clarifying Wound Healing in Streptozotocin-Induced
      Diabetic Rats.
AB  - Diabetes mellitus is a serious public health problem in which a major
      complication is impaired wound healing. Among the strategies developed to foster
      tissue repair is the use of medicinal plants. The bark of Stryphnodendron
      adstringens, which is popularly used as an aid in wound healing, has a documented
      effect on wound repair in normal rats. This study evaluated the healing action of
      the crude extract of S. adstringens in diabetic rats, and its chemical content.
      Compounds present in the crude extract were characterized by mass spectrometry.
      In diabetic rats (streptozotocin 35 mg/kg), two wounds made in the skin were
      treated daily for 4, 7, 10, and 14 days with gel containing 1 % crude extract or
      with base gel. Histological analyses involved the measurement of the length and
      thickness of the re-epithelialized surface, quantification of the number of cells
      in mitosis, and types I and III collagen fibers. Also, cutaneous permeation by
      photoacoustic spectroscopy, and the expression of cyclooxygenase-2 and vascular
      endothelial growth factor by Western blot were assessed. The crude extract
      fingerprint showed masses indicating proanthocyanidins. The crude extract mainly
      stimulated cell migration and proliferation of keratinocytes at the beginning of
      the treatment in addition to stimulating the replacement of type III collagen
      fibers by type I collagen fibers at 10 and 14 days. The photoacoustic
      spectroscopy technique showed that the gel containing 1 % of crude extract
      permeated through the skin to the dermis, where the crude extract was found.
      Vascular endothelial growth factor was stimulated after 7 days of treatment with
      the crude extract and cyclooxygenase-2 at 4, 7, and 10 days. The crude extract of
      S. adstringens acted in tissue repair in wounds in diabetic rats by stimulating
      the production of collagen fibers at the wound site. The crude extract favored
      the formation of a more organized extracellular matrix and filled the entire
      extent of the wound, and also fostered the upregulation of cyclooxygenase-2 and
      vascular endothelial growth factor, which are essential to this process. These
      crude extract actions in diabetic wounds are probably due to the presence of
      proanthocyanidins.

PMID- 26218338
TI  - GABAA Receptor Binding Assays of Standardized Leonurus cardiaca and Leonurus
      japonicus Extracts as Well as Their Isolated Constituents.
AB  - A main traditional use of European Leonurus cardiaca and East Asian Leonurus
      japonicus is in the treatment of neurological disorders such as anxiety,
      depression, nervousness, and as a sedative for insomnia. However, their mechanism
      of action is still under discussion. As anxiety and depressive disorders are
      increasingly being recognized as connected to dysfunctions of the gamma
      aminobutyric acid system, the in vitro effects of standardized L. cardiaca and L
      japonicus extracts as well as five of their isolated constituents, namely, the
      labdane-type isoleosibirin, the novel iridoid 7R-chloro-6-desoxy-harpagide, the
      phenylethanoid lavandulifolioside, and the N-containing compounds stachydrine and
      leonurine, on this type of neuronal receptor were investigated for the first
      time. Extracts of L. cardiaca and L. japonicus, characterized by reversed-phase
      high-performance liquid chromatography determination, as well as their above
      named isolated, possible active constituents of different chemical nature were
      tested in several receptor binding assays at rat GABAA receptors using [(3)H]
      SR95 531 and [(3)H]-Ro-15-1788 (flumazenil)/diazepam control. The L. cardiaca and
      L. japonicus extracts as well as leonurine inhibited the concentration-dependent
      binding of [(3)H]-SR95 531 to the gamma-aminobutyric acid site of the gamma
      aminobutyric acid type A receptor with a high binding affinity: IC50s 21 ug/ml,
      46 ug/ml, and 15 ug/ml, respectively. In contrast, binding to the benzodiazepine
      site of the rat gamma-aminobutyric acid type A receptor had a 15 to 30 times
      lower binding affinity than to the gamma-aminobutyric acid site. The presented
      experiments provide hints that the neurological mechanism of action of L.
      cardiaca and L. japonicus may essentially be based on their interaction to the
      gamma-aminobutyric acid site of the gamma-aminobutyric acid type A receptor,
      while the benzodiazepine site most probably does not contribute to this effect.
      In the case of L. japonicus, these effects can be at least partially explained by
      its leonurine constituent, whereas the active principle of L. cardiaca, which
      does not contain leonurine, is subject to further research as none of the other
      investigated individual constituents displayed significant activity in the
      applied test system.

PMID- 26218339
TI  - Prevention of False-Positive Results: Development of an HPTLC Autographic Assay
      for the Detection of Natural Tyrosinase Inhibitors.
AB  - A simple and rapid high-performance thin-layer chromatography-based autographic
      assay was established to screen plant extracts for the presence of tyrosinase
      inhibiting substances. Three mobile phases were selected for the chromatographic
      separation of different types of extracts. After development, the plate was
      sprayed with the substrate solution Levodopa followed by a solution of the enzyme
      tyrosinase. Several known tyrosinase inhibitors were tested simultaneously as
      positive controls. They were detected as white spots with white light in
      remission from the plate as well as with white light transmitted through the
      plate. Some of the investigated extracts included spots showing a different
      behaviour; some lipophilic substances appeared as white spots in white light
      remission but were black in white light transmission. This behaviour, which could
      lead to false-positive results, was due to poor wettability of the corresponding
      spots. False-positive results were eliminated by adding Triton X-100 to the
      Levodopa solution and drying the plate after 10 minutes incubation with a
      molecular sieve. Tyrosinase inhibitors can be clearly identified as white spots
      against a dark background in white light remission as well as in white light
      transmitted through the plate. The established high-performance thin-layer
      chromatography autographic assay was validated and can be used as a standard
      method for the detection of tyrosinase inhibitors in plant extracts without
      causing false-positive results. 

PMID- 26218340
TI  - Chemical and Biological Investigation of Olive Mill Waste Water - OMWW
      Secoiridoid Lactones.
AB  - Olive mill waste water is the major byproduct of the olive oil industry
      containing a range of compounds related to Olea europaea and olive oil
      constituents. Olive mill waste water comprises an important environmental problem
      in olive oil producing countries, but it is also a valuable material for the
      isolation of high added value compounds. In this study, an attempt to investigate
      the secoiridoid content of olive mill waste water is described with the aid of
      ultrahigh-performance liquid chromatography-electrospray ionization (+/-)-high
      resolution mass spectrometry and centrifugal partition chromatography methods. In
      total, seven secoiridoid lactones were isolated, four of which are new natural
      products. This is the first time that a conjugate of hydroxytyrosol and a
      secoiridoid lactone has been isolated from olive mill waste water and
      structurally characterized. Furthermore, the range of isolated compounds allowed
      for the proposal of a hypothesis for the biotransformation of olive secoiridoids
      during the production of olive mill waste water. Finally, the ability of the
      representative compounds to reduce the intracellular reactive oxygen species was
      assessed with the dichlorofluorescein assay in conjunction with the known
      antioxidant agent hydroxytyrosol. 

PMID- 26218341
TI  - Adsorption of antimony(V) onto Mn(II)-enriched surfaces of manganese-oxide and
      FeMn binary oxide.
AB  - Manganese(IV) oxide [Mn(IV)] potentially oxidizes antimony(III) [Sb(III)] to
      antimony(V) [Sb(V)] and improves Sb removal by FeMn binary oxide (FMBO) through
      an oxidation-adsorption mechanism. This study focused on the effect of Mn(IV)
      reductive dissolution by potassium sulfite (K2SO3) on Sb(V) adsorption onto
      manganese oxide (Mn-oxide) and FMBO. The maximum Sb(V) adsorption (Qmax,Sb(V))
      increased from 1.0 to 1.1 mmol g(-1) for FMBO and from 0.4 to 0.6 mmol g(-1) for
      Mn-oxide after pretreatment with 10 mmol L(-1) K2SO3. The addition of 2.5 mmol L(
      1) Mn(2+) also significantly improved Sb(V) adsorption, and the observed
      Qmax,Sb(V) increased to 1.4 and 1.0 mmol g(-1) for FMBO and Mn-oxide,
      respectively, with pre-adsorbed Mn(2+). Neither K2SO3 nor Mn(2+) addition had any
      effect on Sb(V) adsorption onto iron oxide (Fe-oxide). Mn(2+) introduced by
      either Mn(IV) dissolution or addition tended to form outer-sphere surface
      complexes with hydroxyl groups on Mn-oxide surfaces (MnOOH). Mn(2+) at 2.5 mmol
      L(-1) shifted the isoelectric point (pHiep) from 7.5 to 10.2 for FMBO and from
      4.8 to 9.2 for Mn-oxide and hence benefited Sb(V) adsorption. The adsorption of
      Sb(V) onto Mn(2+)-enriched surfaces contributed to the release of Mn(2+), and the
      X-ray photoelectron spectra also indicated increased binding energy of Mn 2p3/2
      after the adsorption of Sb(V) onto K2SO3-pretreated FMBO and Mn-oxide. Sb(V)
      adsorption involved the formation of inner-sphere complexes and contributed to
      the release of Mn(2+). In the removal of Sb(III) by Mn-based oxides, the
      oxidation of Sb(III) to Sb(V) by Mn(IV) oxides had an effect; however, Mn(IV)
      dissolution and Mn(2+)-enrichment also played an important role.

PMID- 26218342
TI  - Preparation of amino-Fe(III) functionalized mesoporous silica for synergistic
      adsorption of tetracycline and copper.
AB  - Finding effective methods for simultaneous removal of antibiotics and heavy
      metals has attracted increasing concern since both of them are frequently
      detected in aquatic environments. In this study, a novel mesoporous silica
      adsorbent (Fe-N,N-SBA15) contained dual-functional groups was synthesized by
      first grafting di-amino groups on SBA15, and then coordinating Fe(III) onto the
      adsorbent. The adsorbent was then used in the synchronous elimination of
      tetracycline (TC) and Cu(II) from water, which was deeply studied by solution pH,
      kinetics, equilibriums in sole and binary systems. It was found that the
      adsorbent had high affinity for both TC and Cu(II) and synergistic effects on the
      adsorption were found. The solution pH remarkably affected the adsorption due to
      pH-dependent speciation of TC, Cu(II), TC-Cu(II) complex and the surface
      properties of the adsorbent. Increasing adsorption amount of TC and Cu(II) on the
      adsorbent could be attributed to the formation of complex TC-Cu(II) bridging or
      the stronger affinity of the adsorbent for the TC-Cu(II) complex than that for TC
      or Cu(II) separately. FT-IR and XPS studies revealed that Fe(III) and amino
      groups on the adsorbent were complexed with the amide of TC and Cu(II),
      respectively. The recyclabilities of the adsorbent were also evaluated and the Fe
      N,N-SBA15 exhibited good reusability for TC and Cu(II) removal. This study shows
      guidelines and offers an innovative, effective method for the synergistic removal
      of antibiotics and heavy metals from aquatic environments. 

PMID- 26218343
TI  - Indole Glucocorticoid Receptor Antagonists Active in a Model of Dyslipidemia Act
      via a Unique Association with an Agonist Binding Site.
AB  - To further elucidate the structural activity correlation of glucocorticoid
      receptor (GR) antagonism, the crystal structure of the GR ligand-binding domain
      (GR LBD) complex with a nonsteroidal antagonist, compound 8, was determined. This
      novel indole sulfonamide shows in vitro activity comparable to known GR
      antagonists such as mifepristone, and notably, this molecule lowers LDL (-74%)
      and raises HDL (+73%) in a hamster model of dyslipidemia. This is the first
      reported crystal structure of the GR LBD bound to a nonsteroidal antagonist, and
      this article provides additional elements for the design and pharmacology of
      clinically relevant nonsteroidal GR antagonists that may have greater selectivity
      and fewer side effects than their steroidal counterparts. 

PMID- 26218344
TI  - Pain Catastrophizing Predicts Menstrual Pain Ratings in Adolescent Girls with
      Chronic Pain.
AB  - OBJECTIVES: The current study aimed to explore relationships among self-reported
      menstrual pain ratings, acute laboratory pain, pain catastrophizing, and anxiety
      sensitivity in a sample of girls without pain (No Pain group) and girls with a
      chronic pain condition (Chronic Pain group). SETTING: A laboratory at an off
      campus Medical School office building. SUBJECTS: Eighty-four postmenarchal girls
      (43 No Pain, 41 Chronic Pain) ages 10-17 participated in the study. METHODS: All
      participants completed self-report questionnaires assessing menstrual pain, pain
      catastrophizing, and anxiety sensitivity and completed a cold pressor task. Pain
      intensity during the task was rated on a 0 (no pain) to 10 (worst pain possible)
      numeric rating scale. RESULTS: After controlling for age, average menstrual pain
      ratings (without medication) were significantly correlated with cold pressor pain
      intensity for the No Pain group only. In the Chronic Pain group, menstrual pain
      ratings were significantly correlated with pain catastrophizing and anxiety
      sensitivity. In a multiple linear regression analysis, after controlling for age,
      only pain catastrophizing emerged as a significant predictor of menstrual pain
      ratings in the Chronic Pain group. CONCLUSION: Results demonstrate differences in
      relationships among menstrual pain, acute laboratory pain, and psychological
      variables in girls with no pain compared with girls with chronic pain. In
      addition, pain catastrophizing may be a particularly salient factor associated
      with menstrual pain in girls with chronic pain that warrants further
      investigation.

PMID- 26218345
TI  - Competing Forces during Contact Formation between a Tip and a Single Molecule.
AB  - Sn-phthalocyanine adsorbs on Ag(111) in a physisorbed or a chemisorbed
      configuration. Both structures are contacted with the tip of a combined scanning
      tunneling and atomic force microscope. The tunneling conductances of both
      configurations exhibit similar exponential variations with the tip-molecule
      distance. The short-range forces, however, display nontrivial distance
      dependencies. First-principles calculations reproduce the experimental results.
      Both attractive and repulsive interactions occur between the tip and different
      parts of the molecule due to a combination of bond formation and electrostatic
      interactions with the tip electric dipole. Consequently, deformations occur and
      the force varies in the resulting unexpected fashion. 

PMID- 26218346
TI  - High-resolution high-speed dynamic mechanical spectroscopy of cells and other
      soft materials with the help of atomic force microscopy.
AB  - Dynamic mechanical spectroscopy (DMS), which allows measuring frequency-dependent
      viscoelastic properties, is important to study soft materials, tissues,
      biomaterials, polymers. However, the existing DMS techniques (nanoindentation)
      have limited resolution when used on soft materials, preventing them from being
      used to study mechanics at the nanoscale. The nanoindenters are not capable of
      measuring cells, nanointerfaces of composite materials. Here we present a highly
      accurate DMS modality, which is a combination of three different methods:
      quantitative nanoindentation (nanoDMA), gentle force and fast response of atomic
      force microscopy (AFM), and Fourier transform (FT) spectroscopy. This new
      spectroscopy (which we suggest to call FT-nanoDMA) is fast and sensitive enough
      to allow DMS imaging of nanointerfaces, single cells, while attaining about 100x
      improvements on polymers in both spatial (to 10-70 nm) and temporal resolution
      (to 0.7 s/pixel) compared to the current art. Multiple frequencies are measured
      simultaneously. The use of 10 frequencies are demonstrated here (up to 300 Hz
      which is a rather relevant range for biological materials and polymers, in both
      ambient conditions and liquid). The method is quantitatively verified on known
      polymers and demonstrated on cells and polymers blends. Analysis shows that FT
      nanoDMA is highly quantitative. The FT-nanoDMA spectroscopy can easily be
      implemented in the existing AFMs.

PMID- 26218348
TI  - Does mechanistic modeling of filter strip pesticide mass balance and degradation
      processes affect environmental exposure assessments?
AB  - Vegetative filter strips (VFS) are a widely adopted practice for limiting
      pesticide transport from adjacent fields to receiving waterbodies. The efficacy
      of VFS depends on site-specific input factors. To elucidate the complex and non
      linear relationships among these factors requires a process-based modeling
      framework. Previous research proposed linking existing higher-tier environmental
      exposure models with a well-tested VFS model (VFSMOD). However, the framework
      assumed pesticide mass stored in the VFS was not available for transport in
      subsequent storm events. A new pesticide mass balance component was developed to
      estimate surface pesticide residue trapped in the VFS and its degradation between
      consecutive runoff events. The influence and necessity of the updated framework
      on acute and chronic estimated environmental concentrations (EECs) and percent
      reductions in EECs were investigated across three, 30-year U.S. EPA scenarios:
      Illinois corn, California tomato, and Oregon wheat. The updated framework with
      degradation predicted higher EECs than the existing framework without degradation
      for scenarios with greater sediment transport, longer VFS lengths, and highly
      sorbing and persistent pesticides. Global sensitivity analysis (GSA) assessed the
      relative importance of mass balance and degradation processes in the context of
      other input factors like VFS length (VL), organic-carbon sorption coefficient
      (Koc), and soil and water half-lives. Considering VFS pesticide residue and
      degradation was not important if single, large runoff events controlled
      transport, as is typical for higher percentiles considered in exposure
      assessments. Degradation processes become more important when considering percent
      reductions in acute or chronic EECs, especially under scenarios with lower
      pesticide losses.

PMID- 26218349
TI  - Robustness analysis of uncertain dynamical neural networks with multiple time
      delays.
AB  - This paper studies the problem of global robust asymptotic stability of the
      equilibrium point for the class of dynamical neural networks with multiple time
      delays with respect to the class of slope-bounded activation functions and in the
      presence of the uncertainties of system parameters of the considered neural
      network model. By using an appropriate Lyapunov functional and exploiting the
      properties of the homeomorphism mapping theorem, we derive a new sufficient
      condition for the existence, uniqueness and global robust asymptotic stability of
      the equilibrium point for the class of neural networks with multiple time delays.
      The obtained stability condition basically relies on testing some relationships
      imposed on the interconnection matrices of the neural system, which can be easily
      verified by using some certain properties of matrices. An instructive numerical
      example is also given to illustrate the applicability of our result and show the
      advantages of this new condition over the previously reported corresponding
      results. 

PMID- 26218347
TI  - Chemical Fluorescent Probe for Detection of Abeta Oligomers.
AB  - Aggregation of amyloid beta-peptide (Abeta) is implicated in the pathology of
      Alzheimer's disease (AD), with the soluble, Abeta oligomeric species thought to
      be the critical pathological species. Identification and characterization of
      intermediate species formed during the aggregation process is crucial to the
      understanding of the mechanisms by which oligomeric species mediate neuronal
      toxicity and following disease progression. Probing these species proved to be
      extremely challenging, as evident by the lack of reliable sensors, due to their
      heterogeneous and transient nature. We describe here an oligomer-specific
      fluorescent chemical probe, BoDipy-Oligomer (BD-Oligo), developed through the use
      of the diversity-oriented fluorescent library approach (DOFLA) and high-content,
      imaging-based screening. This probe enables dynamic oligomer monitoring during
      fibrillogenesis in vitro and shows in vivo Abeta oligomers staining possibility
      in the AD mice model. 

PMID- 26218350
TI  - Non-parametric temporal modeling of the hemodynamic response function via a
      liquid state machine.
AB  - Standard methods for the analysis of functional MRI data strongly rely on prior
      implicit and explicit hypotheses made to simplify the analysis. In this work the
      attention is focused on two such commonly accepted hypotheses: (i) the
      hemodynamic response function (HRF) to be searched in the BOLD signal can be
      described by a specific parametric model e.g., double-gamma; (ii) the effect of
      stimuli on the signal is taken to be linearly additive. While these assumptions
      have been empirically proven to generate high sensitivity for statistical
      methods, they also limit the identification of relevant voxels to what is already
      postulated in the signal, thus not allowing the discovery of unknown correlates
      in the data due to the presence of unexpected hemodynamics. This paper tries to
      overcome these limitations by proposing a method wherein the HRF is learned
      directly from data rather than induced from its basic form assumed in advance.
      This approach produces a set of voxel-wise models of HRF and, as a result,
      relevant voxels are filterable according to the accuracy of their prediction in a
      machine learning framework. This approach is instantiated using a temporal
      architecture based on the paradigm of Reservoir Computing wherein a Liquid State
      Machine is combined with a decoding Feed-Forward Neural Network. This splits the
      modeling into two parts: first a representation of the complex temporal
      reactivity of the hemodynamic response is determined by a universal global
      "reservoir" which is essentially temporal; second an interpretation of the
      encoded representation is determined by a standard feed-forward neural network,
      which is trained by the data. Thus the reservoir models the temporal state of
      information during and following temporal stimuli in a feed-back system, while
      the neural network "translates" this data to fit the specific HRF response as
      given, e.g. by BOLD signal measurements in fMRI. An empirical analysis on
      synthetic datasets shows that the learning process can be robust both to noise
      and to the varying shape of the underlying HRF. A similar investigation on real
      fMRI datasets provides evidence that BOLD predictability allows for
      discrimination between relevant and irrelevant voxels for a given set of stimuli.

PMID- 26218351
TI  - Scoring Tools for the Analysis of Infant Respiratory Inductive Plethysmography
      Signals.
AB  - Infants recovering from anesthesia are at risk of life threatening Postoperative
      Apnea (POA). POA events are rare, and so the study of POA requires the analysis
      of long cardiorespiratory records. Manual scoring is the preferred method of
      analysis for these data, but it is limited by low intra- and inter-scorer
      repeatability. Furthermore, recommended scoring rules do not provide a
      comprehensive description of the respiratory patterns. This work describes a set
      of manual scoring tools that address these limitations. These tools include: (i)
      a set of definitions and scoring rules for 6 mutually exclusive, unique patterns
      that fully characterize infant respiratory inductive plethysmography (RIP)
      signals; (ii) RIPScore, a graphical, manual scoring software to apply these rules
      to infant data; (iii) a library of data segments representing each of the 6
      patterns; (iv) a fully automated, interactive formal training protocol to
      standardize the analysis and establish intra- and inter-scorer repeatability; and
      (v) a quality control method to monitor scorer ongoing performance over time. To
      evaluate these tools, three scorers from varied backgrounds were recruited and
      trained to reach a performance level similar to that of an expert. These scorers
      used RIPScore to analyze data from infants at risk of POA in two separate,
      independent instances. Scorers performed with high accuracy and consistency,
      analyzed data efficiently, had very good intra- and inter-scorer repeatability,
      and exhibited only minor confusion between patterns. These results indicate that
      our tools represent an excellent method for the analysis of respiratory patterns
      in long data records. Although the tools were developed for the study of POA,
      their use extends to any study of respiratory patterns using RIP (e.g., sleep
      apnea, extubation readiness). Moreover, by establishing and monitoring scorer
      repeatability, our tools enable the analysis of large data sets by multiple
      scorers, which is essential for longitudinal and multicenter studies. 

PMID- 26218352
TI  - Reproducing topography and roughness of osteoconductive biomaterials in a
      microfluidic device.

PMID- 26218353
TI  - Validation of a Skin-Lesion Image-Matching Algorithm Based on Computer Vision
      Technology.
AB  - BACKGROUND: Melanoma incidence is increasing globally, but consistently accurate
      skin-lesion classification methods remain elusive. We developed a simple software
      system to classify potentially all types of skin lesions. In the current study,
      we evaluated the system's ability to identify melanomas with a diameter of 10 mm
      or larger. MATERIALS AND METHODS: The skin-lesion classification system is
      composed of a proprietary database of nearly 12,000 diagnosed skin-lesion images
      and a computer algorithm based on the principles of content-based image
      retrieval. The algorithm compares characteristics of new skin-lesion images with
      images in the database to identify the nearest-match diagnosis. RESULTS: Nearly
      all classification accuracy measures for this new system exceeded 90%, with
      results for sensitivity of 90.4% (95% confidence interval, 85.6-93.7%),
      specificity of 91.5% (85.4-95.2%), positive predictive value of 94.5% (90.4
      96.9%), negative predictive value of 85.5% (78.7-90.4%), and overall
      classification accuracy of 90.8% (87.2-93.4%). CONCLUSIONS: The image-matching
      algorithm performed with high accuracy for the classification of larger
      melanomas. Furthermore, the system does not require a dermoscope or any other
      specialized hardware; any close-focusing camera will do. This system has the
      potential to be an inexpensive and accurate tool for the evaluation of skin
      lesions in ethnically and geographically diverse populations.

PMID- 26218354
TI  - What can I believe? Peer review, innovation, and 90 years of academic medicine.

PMID- 26218355
TI  - Privacy versus confidentiality: more on the use of the electronic health record
      for learning.

PMID- 26218356
TI  - In reply to Brisson and colleagues.

PMID- 26218357
TI  - Differentiating standardized clinical assessment and management plans from
      clinical practice guidelines.

PMID- 26218358
TI  - The role of professional medical education societies in fostering professional
      identity.

PMID- 26218359
TI  - Where are the women?

PMID- 26218360
TI  - It's time to snuff out the "anatomical snuff box".

PMID- 26218361
TI  - The evaluation blues.

PMID- 26218362
TI  - Artist's statement: the changing face of medicine.

PMID- 26218364
TI  - "So much for that" by Lionel Shriver. Commentary.

PMID- 26218365
TI  - Trivial medicine.

PMID- 26218366
TI  - Evidence-based care pathway for cellulitis improves process, clinical, and cost
      outcomes.
AB  - BACKGROUND: Cellulitis is a common infection with wide variation of clinical
      care. OBJECTIVE: To implement an evidence-based care pathway and evaluate changes
      in process metrics, clinical outcomes, and cost for cellulitis. DESIGN: A
      retrospective observational pre-/postintervention study was performed. SETTING:
      University of Utah Health Care, a 500-bed academic medical center in Salt Lake
      City, Utah. PATIENTS: All patients 18 years or older admitted to the emergency
      department observation unit or hospital with a primary diagnosis of cellulitis.
      INTERVENTION: Development of an evidence-based care pathway for cellulitis
      embedded into the electronic medical record with education for all emergency and
      internal medicine physicians. MEASUREMENTS: Primary outcome of broad-spectrum
      antibiotic use. Secondary outcomes of computed tomography/magnetic resonance
      imaging orders, length of stay (LOS), 30-day readmission, and pharmacy, lab,
      imaging, and total facility costs. RESULTS: A total of 677 visits occurred,
      including 370 visits where order sets were used. Among all patients, there was a
      59% decrease in the odds of ordering broad-spectrum antibiotics (P < 0.001), 23%
      decrease in pharmacy cost (P = 0.002), and 13% decrease in total facility cost (P
      = 0.006). Compared to patients for whom order sets were not used, patients for
      whom order sets were used had a 75%, 13%, and 25% greater decrease in the odds of
      ordering broad-spectrum antibiotics (P < 0.001), clinical LOS (P = 0.041), and
      pharmacy costs (P = 0.074), respectively. CONCLUSION: The evidence-based care
      pathway for cellulitis improved care at an academic medical center by reducing
      broad-spectrum antibiotic use, pharmacy costs, and total facility costs without
      an adverse change in LOS or 30-day readmissions.

PMID- 26218367
TI  - Evaluation of Group Acupuncture for Cancer-Related Symptoms: A Retrospective
      Analysis.
AB  - BACKGROUND: Acupuncture is being used for treatment of cancer-related symptoms in
      numerous settings, yet empirical evidence supporting the effects of acupuncture
      in this setting is lacking. Group acupuncture is an economical way to provide
      acupuncture to patients at a reduced cost. OBJECTIVE: In this retrospective study
      we sought to evaluate the effects of group acupuncture on specific cancer-related
      symptoms in persons receiving outpatient cancer treatment. METHODS: Patients were
      receiving group acupuncture treatments through an integrative oncology program in
      a large community oncology practice in west central Florida. A short patient
      completed assessment of seven basic cancer-related symptoms using a 0-10 numeric
      rating scale was completed at each acupuncture treatment. Basic demographic
      information, including age, gender, race/ethnicity, and cancer type was obtained
      from the medical record. Paired sample t-tests were used to evaluate differences
      in symptoms before the first treatment and at the fourth treatment. RESULTS:
      Fifty patients completed at least four weekly acupuncture treatments in 2014.
      Forty-three of them completed symptom assessments and were included in this
      analysis. The mean age of participants was 66.4 years. The majority of patients
      were white, non-Hispanic, and female. No significant improvement in symptoms were
      identified at the third treatment. At the time of the fourth group acupuncture,
      participants reported significantly less pain/numbness and problems with
      digestion. DISCUSSION: The results of this study provide evidence to support the
      efficacy of group acupuncture for pain, neuropathy, and digestive problems in
      persons with cancer. A minimum of four weekly treatments may be necessary before
      improvements are noted. Limitations include a retrospective design, incomplete
      symptom evaluation, and possible response bias. Future studies of group
      acupuncture for cancer-related symptoms should utilize a prospective, controlled
      design, use validated measures to thoroughly evaluate targeted symptoms, and
      include a more racially and ethnically diverse sample.

PMID- 26218368
TI  - Community Perceptions on Integrating Animal Vaccination and Health Education by
      Veterinary and Public Health Workers in the Prevention of Brucellosis among
      Pastoral Communities of South Western Uganda.
AB  - BACKGROUND: Brucellosis is a zoonotic disease of veterinary, public health, and
      economic significance in most developing countries, yet there are few studies
      that show integrated human and veterinary health care intervention focusing on
      integration at both activity and actors levels. The aim of our study, therefore,
      was to explore community perceptions on integration of animal vaccination and
      health education by veterinary and public health workers in the management of
      brucellosis in Uganda. METHODS: This study used a qualitative design where six
      Focus Group Discussions (FGDs) that were homogenous in nature were conducted, two
      from each sub-county, one with the local leaders, and another with pastoralists
      and farmers. Five Key Informant Interviews (KIIs) with two public health workers
      and three veterinary extension workers from three sub-counties in Kiruhura
      district, Uganda were conducted. All FGDs were conducted in the local language
      and tape recorded with consent from the participants. KIIs were in English and
      later transcribed and analyzed using latent content data analysis method.
      RESULTS: All the groups mentioned that they lacked awareness on brucellosis
      commonly known as Brucella and its vaccination in animals. Respondents perceived
      improvement in human resources in terms of training and recruiting more health
      personnel, facilitation of the necessary activities such as sensitization of the
      communities about brucellosis, and provision of vaccines and diagnostic tests as
      very important in the integration process in the communities. The FGD
      participants also believed that community participation was crucial for
      sustainability and ownership of the integration process. CONCLUSIONS: The
      respondents reported limited knowledge of brucellosis and its vaccination in
      animals. The community members believed that mass animal vaccination in
      combination with health education about the disease is important and possible if
      it involves government and all other stakeholders such as wildlife authorities,
      community members, local to national political leaders, as well as the technical
      personnel from veterinary, medical and public health sectors since it affects
      both humans and animals.

PMID- 26218370
TI  - Hollow Metal-Incorporated Monodispersed Mesoporous Silica Spheres.
AB  - Expansion of mesopores and concomitant incorporation of metal species into
      mesoporous silica particles was achieved through the hydrothermal treatment of
      monodispersed mesoporous silica spheres in an aqueous metal salt solution.
      Mesopore size was increased to 24 nm from 2.2 nm while retaining monodispersed
      spherical shape. Surprisingly, hollow spheres were produced when Mg salt was
      used. Incorporation of metal species led to drastic improvement in adsorption
      performance. The amount of Rhodamine B adsorbed was increased by 27 times. 

PMID- 26218369
TI  - Virtual analysis of structurally diverse synthetic analogs as inhibitors of snake
      venom secretory phospholipase A2.
AB  - Due to the toxic pathophysiological role of snake venom phospholipase A2 (PLA2 ),
      its compelling limitations to anti-venom therapy in humans and the need for
      alternative therapy foster considerable pharmacological interest towards search
      of PLA2 specific inhibitors. In this study, an integrated approach involving
      homology modeling, molecular dynamics and molecular docking studies on VRV-PL-V
      (Vipera russellii venom phospholipase A2 fraction-V) belonging to Group II-B
      secretory PLA2 from Daboia russelli pulchella is carried out in order to study
      the structure-based inhibitor design. The accuracy of the model was validated
      using multiple computational approaches. The molecular docking study of this
      protein was undertaken using different classes of experimentally proven,
      structurally diverse synthetic inhibitors of secretory PLA2 whose selection is
      based on IC50 value that ranges from 25 MUM to 100 MUM. Estimation of protein
      ligand contacts by docking analysis sheds light on the importance of His 47 and
      Asp 48 within the VRV-PL-V binding pocket as key residue for hydrogen bond
      interaction with ligands. Our virtual analysis revealed that compounds with
      different scaffold binds to the same active site region. ADME analysis was also
      further performed to filter and identify the best potential specific inhibitor
      against VRV-PL-V. Additionally, the e-pharmacophore was generated for the best
      potential specific inhibitor against VRV-PL-V and reported here. The present
      study should therefore play a guiding role in the experimental design of VRV-PL-V
      inhibitors that may provide better therapeutic molecular models for PLA2
      recognition and anti-ophidian activity.

PMID- 26218371
TI  - The examination of superior mesenteric artery circulation in fetus during
      pregnancy.
AB  - OBJECTIVE: The aim of the study was a comprehensive examination of the
      circulation of superior mesenteric artery in different weeks of pregnancy using
      Doppler ultrasound examination. METHODS: The study was conducted at the Clinic of
      Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University,
      Slovakia between the years 2008 and 2012. Dynamics and changes in superior
      mesenteric artery circulation were studied in 856 women. Results of Doppler
      examination were processed and subsequently evaluated for each gestational week
      separately. RESULTS: We found that changes in resistance index of superior
      mesenteric artery are slower and have a tendency to decrease as a consequence of
      a gradual decrease in vascular resistance. The changes in pulsatility index are
      different in nature; there is a tendency for there are to be repeating periods of
      higher and then lower values, which are subject to a more pronounced dependence
      on flow rate, especially end diastolic velocity, and Vmean. CONCLUSIONS: This
      article and its results bring a new, comprehensive view not only of physiological
      changes in the splanchnic circulation, but also of changes that may be subject to
      a certain extent, not only to the sex, but primarily to the weight of the fetus,
      which, of course, indirectly reflects its metabolic and respiratory demands.

PMID- 26218372
TI  - Embrace the Change: Incorporating Single-Stage Implant Breast Reconstruction into
      Your Practice.
AB  - BACKGROUND: Multiple studies have reported on the safety of nipple-sparing
      mastectomy and low complication rates associated with single-stage implant breast
      reconstruction. Yet many plastic surgeons continue to be resistant to change.
      This article presents the senior author's (M.A.C.) experience during his
      transition period from the latissimus dorsi flap with adjustable implants to a
      "one-and-done" approach using shaped implants and fetal bovine acellular dermal
      matrix. METHODS: A literature review was performed selecting articles discussing
      single-stage implant reconstruction, indications, outcomes, technique, and
      complications. Additional articles were selected after review of the references
      of identified articles. Clinical pearls discussed include patient selection,
      implant selection, and mastectomy incision choices, with a detailed description
      of the senior author's operative technique. RESULTS: Twenty-seven single-stage
      implant reconstructions were performed. Average mastectomy weight was 343.82 g.
      The average implant volume was 367 cc. Shaped implants were most commonly used.
      Acellular dermal matrix was used in all breasts. Complications included erythema
      requiring intravenous antibiotics (three patients), skin ischemia caused by
      methylene blue (one patient), seroma (one patient), unilateral partial nipple
      necrosis (one patient), mastectomy skin necrosis (one patient), and
      exposed/infected implants that were salvaged using a sequential irrigation
      protocol described by Sforza et al. in 2014 (two patients). CONCLUSIONS: Breast
      reconstruction after mastectomy has evolved toward less invasive, single-stage
      procedures. Aesthetic refinements include nipple-sparing mastectomy, use of
      acellular dermal matrix, shaped implants, and fat grafting. Selected patients
      will benefit from a one-and-done breast implant reconstruction with no additional
      oncologic risk. Surgeons must embrace the change and provide their patients with
      a procedure that will offer the best aesthetic outcomes. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, IV.

PMID- 26218373
TI  - C-Y Trilobed Flap for Improved Nipple-Areola Complex Reconstruction.
AB  - Nipple-areola complex reconstruction has been shown to improve breast
      reconstruction patients' overall satisfaction. Trilobed flap variations are some
      of the more commonly used flaps for nipple-areola complex reconstruction. The
      donor-site scar frequently extends outside the width of an ideal areolar tattoo
      diameter. There have been many modifications to the original flap design, but
      none of them addresses the length of the donor-site scar. The technique described
      uses a triangular stitch in the donor site to limit the length of the scar. This
      also creates tiny dog-ears within the future areola zone that give a natural
      wrinkled appearance when tattooed. 

PMID- 26218374
TI  - Strategies for Aesthetic Reshaping of the Postpartum Patient.
AB  - Statistics reflect that pregnancies are occurring at a later age, multiple births
      are becoming more common, and a sizeable population--with a keen interest in
      nutrition, fitness, and a continued desire to retain a youthful figure--is aging.
      Consequently, postpartum reshaping is a priority for many women, enough so that
      the phrase "mommy makeover" has entered the vernacular. In this article, the
      senior author's practice was evaluated to explore patient goals, methods, and
      outcomes in reshaping the postpartum abdomen. A literature review was conducted
      to assess the state of the art in methods to meet these goals. The postpartum
      patient often uses her prepregnancy appearance as a barometer for her
      postpregnancy goals. Although aging is one force motivating women to pursue
      abdominoplasty, the majority desires the correction of changes related to
      pregnancy. The abdomen and breasts are the regions most visibly affected by
      pregnancy, although numerous aesthetic units of the trunk and surrounding regions
      concern patients seeking postpartum body contouring and they may be part of the
      patient's perception and idealization of her appearance. Abdominoplasty is
      central to postpartum body contouring, and numerous strategies such as concurrent
      flap, flank, or mons pubis liposuction and waistline enhancement methods are
      integral components of it. Consideration should also be given to the multiple
      body areas affected by pregnancy that may enhance the patient's overall
      appearance. In the appropriate context, multiple procedures can be safely and
      effectively combined to address the various regions affected by postpartum
      changes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 26218375
TI  - Scarpa Fascia Preservation in Abdominoplasty: Does It Preserve the Lymphatics?
AB  - BACKGROUND: The course of the cutaneous lymphatic collectors of the abdominal
      wall in relation to the Scarpa fascia is unclear in the literature. Preserving
      the Scarpa fascia in the lower abdomen to reduce the seroma rate following
      abdominoplasty has been suggested based on the assumption that the lower
      abdominal lymphatics run deep to this layer along their entire course. METHODS:
      Using the previously described technique, the superficial lymphatic drainage of
      eight hemiabdomen specimens from four fresh human cadavers was investigated.
      RESULTS: The upper and lower abdominal collectors originated at the umbilical and
      midline watershed areas in a subdermal plane by the union of precollectors
      draining the dermis. In the lower abdomen, the depth of the collectors gradually
      increased in the subcutaneous fat as they coursed toward the groin. They
      eventually pierced the Scarpa fascia before draining into the superficial
      inguinal nodes located deep to this layer. The transition from the supra- to the
      infra-Scarpa fascia plane occurred within 2 to 3 cm of the inguinal ligament in
      95 percent of the collectors. CONCLUSION: In the four cadavers studied,
      preserving the Scarpa fascia during abdominoplasty would not preserve the lower
      abdominal collectors.

PMID- 26218376
TI  - Anatomical and Round Breast Implants: How to Select and Indications for Use.
AB  - Choosing between round and anatomical form-stable implants is a key decision in
      the process of breast augmentation. Anatomical devices have been subject to a
      number of misconceptions that have limited their use. However, in optimal
      clinical practice, the benefits and risks of both anatomical and round implants
      should be considered for any given patient. Patient and surgeon education is
      fundamental in ensuring that misunderstandings are addressed. The choice between
      anatomical and round devices should be based on a combination of patient desires,
      anatomy, and surgical history. This report presents experience-based
      recommendations on indications and contraindications for each type, and a
      proposed algorithm for decision making in clinical practice. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 26218377
TI  - Discussion: Anatomical and Round Implants: How to Select and Indications for Use.

PMID- 26218378
TI  - Lymphatic Territories (Lymphosomes) in Swine: An Animal Model for Future
      Lymphatic Research.
AB  - BACKGROUND: The swine is a common preclinical large-animal model for medical
      research because of the resemblance of its tissue structures to those of humans.
      However, the lymphatic system in swine is poorly understood. The authors
      investigated the lymphatic system and defined territories (lymphosomes) in swine
      using the microinjection technique. METHODS: Six swine (two male and four female
      17.5- to 50-kg Sus domesticus) were used. Real-time indocyanine green
      fluorescence lymphography was performed in four live swine. After the animals
      were killed, the authors injected a radiocontrast mixture consisting of barium
      sulfate and hydrogen peroxide with red acrylic dye directly into lymphatic
      vessels in six swine carcasses. Courses of the lymphatic vessel were analyzed
      radiographically. The lymphatic vessels were dissected meticulously and chased
      until they connected to the first-tier (sentinel) lymph node. This procedure was
      repeated throughout the body until all the relationships between the lymphatic
      vessels and lymph nodes were defined. RESULTS: The authors successfully mapped
      the superficial lymphatic vessels and their corresponding lymph nodes.
      Indocyanine green fluorescence lymphography and subsequent radiography revealed
      that the swine lymphatic system contained seven lymphosomes: parotid, mandibular,
      dorsal cervical, ventral cervical, subiliac, inguinal, and popliteal territories.
      Of note, no lymph nodes existed in the superficial axillary region. CONCLUSIONS:
      The swine could be a useful large-animal model for lymphatic research because of
      the anatomical consistency of the lymphosomes among animals and the sizable
      lymphatic vessels. However, swine lack the superficial axillary lymph node found
      in humans, suggesting that swine may not be a good model for breast cancer
      related lymphedema.

PMID- 26218379
TI  - Atypical Infections versus Inflammatory Conditions of the Hand: The Role of
      Imaging in Diagnosis.
AB  - Atypical infections may manifest in the setting of low clinical suspicion and,
      because of some similarity to other inflammatory conditions regarding their
      clinical and imaging findings, misdiagnosis or delayed diagnosis is not
      infrequent. The latter may lead to elevated risk of severe bone and joint
      destruction, and higher morbidity. This review addresses the challenging subject
      of discussing the imaging characteristics of atypical infections and a variety of
      inflammatory conditions of the hand, and emphasizes the key points that assist in
      the differentiation of the two broad clinical categories of infections versus
      inflammatory causes. 

PMID- 26218380
TI  - Google Glass as an Alternative to Standard Fluoroscopic Visualization for
      Percutaneous Fixation of Hand Fractures: A Pilot Study.
AB  - This pilot study investigated the feasibility of Google Glass to assist
      visualization of fluoroscopic images during percutaneous pinning of hand
      fractures. Cadavers were used to compare total time to pin each fracture and
      total number of radiographs per fracture from a mini C-arm. A FluoroScan monitor
      was used for radiographic visualization compared to projecting the images in the
      Google Glass display. All outcome measures significantly improved for proximal
      phalanx fractures (127 versus 86 seconds, p = 0.017; 5.3 versus 2.2 images, p =
      0.003), and fewer images were obtained during fixation of metacarpal fractures
      using Google Glass compared with traditional techniques (6.4 versus 3.6, p <
      0.001). Typical FluoroScan monitor placement may require the surgeon to alter
      focus away from the operative field, whereas Google Glass allows constant
      attention directed toward the operative field. 

PMID- 26218381
TI  - Chronic Otitis Media with Effusion Is Associated with Increased Risk of Secondary
      Speech Surgery.
AB  - BACKGROUND: Velopharyngeal insufficiency and chronic otitis media with effusion
      following primary cleft palate repair can be attributed to persistent
      abnormalities in the levator and tensor veli palatini muscles, respectively. The
      purpose of this case-control study was to examine the association between otitis
      media with effusion requiring myringotomy tubes and the need for secondary speech
      surgery. METHODS: Records of patients who underwent primary palatoplasty at the
      authors' institution from 1990 to 2006 were reviewed. Data included age at
      primary palatoplasty, sex, Veau classification, surgeon, number of
      postpalatoplasty myringotomy tube procedures, hearing loss, 22q deletion syndrome
      diagnosis, and fistula. The primary outcome was need for secondary speech
      surgery. RESULTS: Of 249 patients meeting inclusion criteria, forty-four patients
      (17.7 percent) had secondary speech surgery recommended or performed. Univariate
      analysis revealed a significant association between Veau classification, 22q
      deletion syndrome diagnosis, and two or more myringotomy tube procedures with
      secondary speech surgery. Adjusting for multiple covariates, children requiring
      two or more myringotomy tubes were 2.55 times more likely to require secondary
      speech surgery than patients who required one or fewer myringotomy tubes
      procedures (95 percent CI, 1.24 to 5.21; p = 0.009). CONCLUSIONS: The authors
      demonstrate that chronic otitis media with effusion requiring two or more
      myringotomy tube procedures is associated with a significantly increased
      likelihood of requiring secondary speech surgery. Using otitis media with
      effusion as a clinical predictor for secondary velopharyngeal insufficiency could
      lead to early identification of at-risk patients in need of intensive speech
      therapy and timely secondary speech surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Risk, III.

PMID- 26218382
TI  - Optimizing Hybrid Occlusion in Face-Jaw-Teeth Transplantation: A Preliminary
      Assessment of Real-Time Cephalometry as Part of the Computer-Assisted Planning
      and Execution Workstation for Craniomaxillofacial Surgery.
AB  - BACKGROUND: The aesthetic and functional outcomes surrounding Le Fort-based, face
      jaw-teeth transplantation have been suboptimal, often leading to posttransplant
      class II/III skeletal profiles, palatal defects, and "hybrid malocclusion."
      Therefore, a novel technology-real-time cephalometry-was developed to provide the
      surgical team instantaneous, intraoperative knowledge of three-dimensional
      dentoskeletal parameters. METHODS: Mock face-jaw-teeth transplantation operations
      were performed on plastic and cadaveric human donor/recipient pairs (n = 2).
      Preoperatively, cephalometric landmarks were identified on donor/recipient
      skeletons using segmented computed tomographic scans. The computer-assisted
      planning and execution workstation tracked the position of the donor face-jaw
      teeth segment in real time during the placement/inset onto recipient, reporting
      pertinent hybrid cephalometric parameters from any movement of donor tissue. The
      intraoperative data measured through real-time cephalometry were compared to
      posttransplant measurements for accuracy assessment. In addition, posttransplant
      cephalometric relationships were compared to planned outcomes to determine face
      jaw-teeth transplantation success. RESULTS: Compared with postoperative data, the
      real-time cephalometry-calculated intraoperative measurement errors were 1.37 +/-
      1.11 mm and 0.45 +/- 0.28 degrees for the plastic skull and 2.99 +/- 2.24 mm and
      2.63 +/- 1.33 degrees for the human cadaver experiments. These results were
      comparable to the posttransplant relations to planned outcome (human cadaver
      experiment, 1.39 +/- 1.81 mm and 2.18 +/- 1.88 degrees; plastic skull experiment,
      1.06 +/- 0.63 mm and 0.53 +/- 0.39 degrees). CONCLUSION: Based on this
      preliminary testing, real-time cephalometry may be a valuable adjunct for
      adjusting and measuring "hybrid occlusion" in face-jaw-teeth transplantation and
      other orthognathic surgical procedures.

PMID- 26218383
TI  - Long-Term Outcomes of Rectosigmoid Neocolporrhaphy in Male-to-Female Gender
      Reassignment Surgery.
AB  - BACKGROUND: Favorable outcomes of rectosigmoid neocolporrhaphy have previously
      been reported. Unfortunately, rectosigmoid transfers are still perceived
      negatively, usually relegated to secondary vaginoplasties. This study aims to
      provide an objective investigation into the safety and efficacy of rectosigmoid
      neocolporrhaphy for vaginoplasty in male-to-female transsexual patients. METHODS:
      A retrospective review was performed on male-to-female patients who had undergone
      rectosigmoid neocolporrhaphy performed by the senior author. Patient data
      including demographics, medical history, complications, and the need for revision
      surgery were obtained. Direct inquires were conducted to determine patients'
      level of satisfaction with appearance, sexual function, and ease of postoperative
      recovery. RESULTS: Eighty-three patients were included over the course of 22
      years, with an average clinical follow-up of 2.2 years (83 patients) and phone
      interview follow-up of 23 years (21 patients). Overall, the patients were
      healthy, with minimal comorbidities. Forty-eight patients (58 percent) had
      complications, but the majority (83.3 percent) were minor and consisted mainly of
      introital stricture or excessive protrusion of the corpus spongiosum. Smoking was
      associated with higher complication rates (p = 0.05), especially stricture
      formation. Excessive mucorrhea occurred in 28.6 percent but resolved after the
      first year. Overall patient satisfaction with appearance and sexual function was
      high. CONCLUSIONS: This study is one of the largest and longest reported series
      of rectosigmoid transfers for vaginoplasty in transsexual patients. Rectosigmoid
      neocolporrhaphies have many times been recommended for secondary or revision
      surgery when other techniques, such as penile inversion, have failed. However,
      the authors believe the rectosigmoid transfer is safe and efficacious, and it
      should be offered to male-to-female patients for primary vaginoplasty. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 26218384
TI  - Avoiding Skin Grafts: The Keystone Flap in Cutaneous Defects.
AB  - The Keystone Design Perforator Island Flap is a fasciocutaneous perforator flap
      resembling two end-to-end VY flaps. We used a modification of the original design
      to avoid extending the incision into an elliptical pattern, and maintained a
      trailing skin bridge whilst incising fascia in a tunneling fashion. Thirty
      patients underwent 32 flaps mainly on the lower leg to close defects that would
      traditionally require skin grafting. All flaps survived completely, with minor
      complications in four patients. All but five patients were allowed unrestricted
      ambulation after surgery. The modified design is straightforward to learn, has
      reliable perfusion, and provides a simpler recovery for patients. CLINICAL
      QUESTIONS/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 26218386
TI  - A Propensity-Matched Analysis of the Influence of Breast Reconstruction on
      Subsequent Development of Lymphedema.
AB  - BACKGROUND: Recent literature demonstrates a lower incidence of lymphedema with
      breast reconstruction. This study compared the incidence of lymphedema after
      axillary dissection in a propensity-matched cohort of patients with and without
      immediate breast reconstruction. METHODS: A review of patients undergoing
      axillary lymphadenectomy with or without immediate breast reconstruction from
      January 1, 2000, to July 1, 2013, was conducted. Comorbidities, cancer treatment,
      operative characteristics, and pathologic findings were reviewed. The primary
      outcome was postoperative lymphedema. Univariate analysis identified baseline
      differences between the patient groups. Cohorts were propensity-matched by age,
      body mass index greater than 30 kg/m, adjuvant radiation therapy, cardiovascular
      disease, and hypertension. Subsequent multivariate regression was performed to
      identify independent predictors of lymphedema among matched patients. RESULTS: A
      total of 4647 patients underwent breast cancer resection, with 1955 having
      axillary lymphadenectomy (no reconstruction, n = 1200; autologous, n = 563;
      implant-based, n = 192). Matching yielded a cohort of 239 reconstruction and 239
      no-reconstruction patients demonstrating no differences in age, body mass index,
      hypertension, adjuvant radiation therapy, or axillary dissection extent. With
      55.9 months' follow-up, postoperative lymphedema was diagnosed in 94 patients
      (19.7 percent). Reconstruction patients developed lymphedema in 19.2 percent of
      cases versus 20.1 percent for no- reconstruction patients (p = 0.82). Regression
      identified two independent predictors of lymphedema: postoperative radiation
      therapy (OR, 2.90; p < 0.001) and obesity (OR, 2.36; p < 0.001). CONCLUSIONS:
      This study demonstrates a 19.7 percent incidence of lymphedema following axillary
      lymphadenectomy. Reconstruction does not appear to alter lymphedema risk, whereas
      postoperative radiation therapy, obesity, and extensive axillary dissection
      greatly increase risk. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 26218387
TI  - Breast Implant-Associated Anaplastic Large Cell Lymphoma: Proposal for a
      Monitoring Protocol.
AB  - BACKGROUND: The authors report four cases of breast implant-associated anaplastic
      large cell lymphoma (ALCL) from a single institution and propose a
      multidisciplinary protocol. METHODS: From 2012 to 2014, four breast implant
      associated ALCL cases were diagnosed. The authors performed the original
      operation, and no patients were referred to their practice. Cases 1, 2, and 4
      were CD4/CD30/ALK ALCL with previous textured-implant reconstruction, whereas
      case 3 was CD8/CD30/ALK ALCL with previous polyurethane-implant augmentation. A
      retrospective study of all patients who underwent breast implant positioning was
      performed to identify any misdiagnosed cases. RESULTS: Of 483 patients, 226
      underwent reconstruction with latissimus dorsi flap and prosthesis, 115 had skin
      sparing/nipple-sparing mastectomy and prosthesis, 117 underwent an
      expander/implant procedure, and 25 underwent breast augmentation. Fifty-eight
      cases (12 percent) underwent implant replacement for capsular contracture, 15
      (3.1 percent) experienced late-onset seroma, and four (0.83 percent) had both
      capsular contracture and seroma. Seventy-seven symptomatic patients (16 percent)
      underwent surgical revision (capsulectomy/capsulotomy) and/or seroma evacuation.
      The second look on histologic specimens did not identify misdiagnosed cases. A
      multidisciplinary protocol for suspected implant-associated ALCL was established.
      Ultrasound and cytologic examinations are performed in case of periprosthetic
      effusion. If implant-associated ALCL is diagnosed, implant removal with
      capsulectomy is performed. If disseminated disease is detected through positron
      emission tomography/computed tomography of the total body, the patient is
      referred to the oncology department. CONCLUSIONS: A multidisciplinary protocol is
      mandatory for both early diagnosis and patient management. Until definitive data
      emerge regarding the exact etiopathogenesis of breast implant-associated ALCL,
      the authors suggest offering only autologous reconstruction if patients desire
      it. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 26218388
TI  - Lower Eyelid Length.
AB  - BACKGROUND: A numerical measurement of the length of the lower eyelid is valuable
      in understanding the aging process of the lower lid. This study recorded multiple
      values for the lower lid length to provide average values in each age group. This
      measurement will allow surgeons to better assess and treat the lower lid.
      METHODS: Female patients were studied in age groups every decade starting in the
      20- to 29-year-old group and ending in the 90- to 99-year-old group. Twenty
      patients were assessed in each age group for a total of 160 patients. In each age
      group, an average measurement was recorded for the lower lid length. RESULTS: The
      lid length average was 10.4 mm in the 20- to 29-year-old group and increased to
      18.6 mm in the 90- to 99-year-old group. A steady increase in lower lid
      measurements numerically confirms that lower lid length increases with age. For
      each decade, there was an almost linear increase in lower lid length, with the
      greatest increase in the 40- to 49-year-old group. CONCLUSIONS: This study
      numerically confirmed that the lower eyelid length vertically increases with age.
      Documenting that the lower lid does lengthen every decade of life and obtaining
      average numerical values of lower lid length allows physicians insight into the
      expected aging changes and typical amount of lower lid lengthening at each
      decade. This also provides blepharoplasty surgeons another tool to more
      accurately define the aging process and creates a baseline and a potential goal
      in restoring a more youthful lid.

PMID- 26218389
TI  - Discussion: Lower Eyelid Length.

PMID- 26218390
TI  - Objective Clinical Assessment of Posture Patterns after Implant Breast
      Augmentation.
AB  - BACKGROUND: An increased weight of the breasts causes several spinal postural
      alterations that reduce the ability to perform dynamic tasks requiring a stable
      balance. The effects of the increased weight of the breasts on static posture
      after implant breast augmentation have not been investigated yet. METHODS: Forty
      volunteer healthy women were asked to wear different sized breast implants (800,
      400, and 300 g) inside a dedicated sports bra for 61/2 consecutive hours during
      their everyday life activities, 1 day for every implant size. Posture changes
      were assessed with the association of a physiatric clinical examination with a
      static force platform analysis. RESULTS: A significant increase in cervical
      lordosis after the use of 400-g breast implants and upward was demonstrated. This
      alteration was stable between the 400-g and 800-g breast implants. The 400-g (per
      breast) implant might therefore be the load threshold that breaks the cervical
      postural physiologic balance. A significant increase in lumbar lordosis was
      demonstrated only after the use of the 800-g breast implants. The static force
      platform assessment demonstrated a worsening of the balance independent from the
      visual control with the use of 400-g and 800-g implants. CONCLUSIONS: Heavy
      breast implants proved to induce reversible alterations in the spinal curve, and
      400 g is the cutoff for functional physiologic compensation in the short term.
      Such a weight might be considered the safety limit for the use of breast implants
      for cosmetic purposes.

PMID- 26218391
TI  - Effect of Botulinum Toxin Type A on Differentiation of Fibroblasts Derived from
      Scar Tissue.
AB  - BACKGROUND: Although botulinum toxin type A has been shown to inhibit the
      formation of hypertrophic scars, little is known about the underlying mechanisms
      of action. Studies have reported that botulinum toxin type A is able to inhibit
      fibroblast proliferation and transforming growth factor (TGF)-beta1 expression;
      therefore, in this study, the authors evaluated its effect on the differentiation
      of fibroblasts derived from normal and hypertrophic scar tissue. METHODS: Under
      local anesthesia, tissue specimens from 10 scars (five normal mature scars and
      five hypertrophic scars) were obtained from nine patients who visited the
      authors' department for scar revision. Fibroblasts isolated from the tissue
      specimens were cultured until confluent and pretreated with TGF-beta1 to induce
      differentiation before treatment with botulinum toxin type A. Expression of the
      myofibroblast marker alpha-smooth muscle actin in cell cultures was evaluated by
      enzyme-linked immunosorbent assay and quantitative reverse transcription
      polymerase chain reaction. Fibroblast-to-myofibroblast differentiation was
      further evaluated by immunocytochemistry and confocal microscopy. RESULTS: The
      authors' results showed that alpha-smooth muscle actin mRNA and protein levels
      were significantly lower in the botulinum toxin type A-treated group than in the
      control group (treated with TGF-beta1 only) of fibroblasts derived from
      hypertrophic scars, but not fibroblasts derived from normal scars.
      Immunocytochemistry results also showed that fibroblast-to-myofibroblast
      differentiation was significantly decreased after botulinum toxin type A
      treatment in fibroblasts derived from hypertrophic scars. CONCLUSION: The
      authors' results show that botulinum toxin type A directly inhibits fibroblast-to
      myofibroblast differentiation in vitro, and indicate its potential for use in
      treating wounds expected to develop into hypertrophic scars after trauma, burn,
      or surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 26218392
TI  - Effect of N-Acetylcysteine on Adipose-Derived Stem Cell and Autologous Fat Graft
      Survival in a Mouse Model.
AB  - BACKGROUND: Autologous fat grafting is a popular reconstructive technique, but is
      limited by inconsistent graft retention. The authors examined whether a widely
      available, clinically safe antioxidant, N-acetylcysteine, could improve adipose
      derived stem cell survival and graft take when added to tumescent solution during
      fat harvest. METHODS: Inguinal fat pads were harvested from C57BL/6 mice using
      tumescent solution with or without N-acetylcysteine. Flow cytometric,
      proliferation, and differentiation assays were performed on isolated primary
      adipose-derived stem cells and 3T3-L1 preadipocytes treated with or without
      hydrogen peroxide and/or N-acetylcysteine. N-Acetylcysteine-treated or control
      grafts were injected under recipient mouse scalps and assessed by serial micro
      computed tomographic volumetric analysis. Explanted grafts underwent
      immunohistochemical analysis. RESULTS: In culture, N-acetylcysteine protected
      adipose-derived stem cells from oxidative stress and improved cell survival
      following hydrogen peroxide treatment. Combined exposure to both N-acetylcysteine
      and hydrogen peroxide led to a 200-fold increase in adipose-derived stem cell
      proliferation, significantly higher than with either agent alone. N
      Acetylcysteine decreased differentiation of adipose-derived stem cells into
      mature adipocytes, as evidenced by decreased transcription of adipocyte
      differentiation markers and reduced Oil Red-O staining. In vivo, N-acetylcysteine
      treatment resulted in improved graft retention at 3 months compared with control
      (46 versus 17 percent; p = 0.027). N-Acetylcysteine-treated grafts demonstrated
      less fibrosis and inflammation, and a 33 percent increase in adipocyte density
      compared with controls (p < 0.001) that was not associated with increased
      vascularity. CONCLUSION: These findings provide proof of principle for the
      addition of N-acetylcysteine to tumescent harvest solution in the clinical
      setting to optimize fat graft yields.

PMID- 26218393
TI  - Differential Effects of Processing Time and Duration of Collagenase Digestion on
      Human and Murine Fat Grafts.
AB  - BACKGROUND: Autologous fat graft retention is unpredictable, and mechanisms of
      optimization are poorly understood. Attempts at improving retention use
      collagenase experimentally and clinically to isolate the stromal vascular
      fraction to "enhance" fat grafts. However, no standardized duration for
      collagenase digestion or time following fat graft harvest has been established.
      This study investigates the effect of (1) time after fat graft harvest and (2)
      collagenase digestion time on interstitial cell and adipocyte viability in murine
      fat and human lipoaspirate. METHODS: Murine fat and human lipoaspirate were
      incubated ex vivo after harvest at room temperature for 120 minutes. Additional
      groups were incubated with collagenase for increasing 5-minute intervals from 30
      to 60 minutes. Samples from each group were stained with BODIPY to quantify
      intact adipocytes and the LIVE/DEAD kit to quantify interstitial cell viability.
      RESULTS: With increased time after harvest, the number of intact adipocytes in
      murine fat and human lipoaspirate remained unchanged. Human interstitial cells
      were resistant to the effect of increased time ex vivo, whereas murine
      interstitial cells decreased in viability. In both populations, increased
      collagenase digestion time significantly decreased the number of viable
      adipocytes (murine, p <= 0.001; human, p <= 0.001) and interstitial cells
      (murine, p <= 0.001; human, p <= 0.001). CONCLUSIONS: Human and murine adipocytes
      and human interstitial cells appear resistant to deleterious effects of
      increasing time following harvest. However, murine interstitial cells are
      sensitive to increased time and prolonged collagenase digestion. These studies
      highlight the complex cellular components of fat grafts and how they respond
      differentially to time and collagenase digestion.

PMID- 26218394
TI  - Applying the Patient-Reported Outcomes Measurement Information System to Assess
      Upper Extremity Function among Children with Congenital Hand Differences.
AB  - BACKGROUND: Few studies have evaluated self-assessment tools among children with
      congenital hand differences. The authors compared three upper extremity
      disability instruments with the Patient-Reported Outcomes Measurement Information
      System (PROMIS) Pediatric Upper Extremity Item Bank. METHODS: Thirty-three
      children (aged 6 to 17 years) with congenital hand differences completed the
      Pediatric Outcomes Data Collection Instrument; the Michigan Hand Outcomes
      Questionnaire; the Disabilities of the Arm, Shoulder, and Hand questionnaire; and
      the PROMIS Upper Extremity short form and computerized adaptive test. Hand
      function was also assessed, and construct validity and feasibility were examined.
      RESULTS: PROMIS demonstrated good construct validity. Short form and computerized
      adaptive test were highly correlated with Disabilities of the Arm, Shoulder, and
      Hand questionnaire scores (r = 0.80, p < 0.001) and Pediatric Outcomes Data
      Collection Instrument domains (r = 0.70, p < 0.001). PROMIS was moderately
      correlated with the Michigan Hand Outcomes Questionnaire (r = 0.40, p < 0.05).
      PROMIS scores also correlated with grip (r = 0.60, p < 0.001) and pinch strength
      (r = 0.50, p < 0.001). Compared with the Pediatric Outcomes Data Collection
      Instrument and the Disabilities of the Arm, Shoulder, and Hand and Michigan Hand
      Outcomes questionnaires, PROMIS required the least time to complete with fewer
      children requiring assistance. CONCLUSION: The Patient-Reported Outcomes
      Measurement Information System is highly correlated with both functional
      assessment and self-reported function among children with congenital hand
      differences.

PMID- 26218395
TI  - Diagnostic Yield of Cervical Radiographs in Infants with Deformational
      Plagiocephaly.
AB  - BACKGROUND: When evaluating infants with deformational plagiocephaly, cervical
      spine radiographs are often acquired along with skull radiographs to exclude
      segmentation and fusion anomalies as the cause of associated torticollis. The
      diagnostic yield of cervical spine radiographs has not been evaluated in this
      clinical setting. METHODS: The authors retrospectively reviewed the charts of all
      patients who were referred to the University of Texas Southwestern School of
      Medicine, Children's Medical Center (Dallas, Texas) with deformational
      plagiocephaly and torticollis and underwent cervical radiography (anteroposterior
      and lateral views) from 2010 to 2012. The authors reviewed the radiology reports,
      and a single experienced pediatric neuroradiologist again reviewed all
      radiographic studies in which the interpreting radiologist had suggested any bony
      or soft-tissue abnormality. Patient demographics, perinatal data, and physical
      examination findings were collected, and descriptive statistics were calculated.
      RESULTS: There were 730 patients with deformational plagiocephaly and
      torticollis; 49 of 730 reports (6.7 percent) described an abnormality. Of those
      with abnormal radiologic reports that were abnormal, 23 (47 percent) described
      osseous abnormalities, 20 (41 percent) described nonosseous deformities, and six
      (12 percent) described both. Follow-up studies (computed tomography, magnetic
      resonance imaging, and repeated radiography) of those with abnormalities showed
      three infants with true upper cervical spine anomalies that might lead to
      instability of the cervical spine. CONCLUSIONS: There is a low diagnostic yield
      in ordering cervical radiographs in most patients with deformational
      plagiocephaly. Although the radiation exposure is low, cervical radiographs add
      additional cost and may not be warranted as a routine practice in this clinical
      setting. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

PMID- 26218396
TI  - Maternofetal Trauma in Craniosynostosis.
AB  - BACKGROUND: Premature cranial suture fusion may prevent neonatal skull
      malleability during birth, increasing the risk of unplanned cesarean delivery and
      neonatal birth trauma caused by cephalopelvic disproportion. We sought to
      determine the incidence of perinatal maternofetal complications in cases of
      craniosynostosis. METHODS: Records of children presenting with nonsyndromic
      craniosynostosis to a tertiary pediatric hospital from 1996 to 2012 were reviewed
      retrospectively with focus on birth history and birth-related complications.
      RESULTS: Six hundred eighteen births were reviewed. Rates of cesarean delivery
      among mothers of children with craniosynostosis [n = 201 (32.5 percent)] exceeded
      the overall regional rate of 24.5 percent (OR, 1.50; p < 0.0001). Unplanned
      cesarean delivery occurred in 19.7 percent of births, and were most associated
      with nulliparous mothers, breech fetal presentations, and lambdoid or multisuture
      synostosis patterns. Eleven neonates (1.8 percent) exhibited cranial birth
      trauma, including cephalohematoma and subgaleal hematoma. Neonates with sagittal
      or multisuture synostosis patterns were more likely to suffer birth trauma and
      had a higher mean head circumference than those who did not (81st versus 66th
      percentile, p < 0.05). CONCLUSIONS: In the setting of craniosynostosis, birth
      trauma is increased-for mothers in the form of increased cesarean delivery risk,
      and for fetuses in the form of subgaleal and subperiosteal perinatal bleeding.
      Difficult maternal labor may be mediated especially by multisuture or lambdoid
      synostosis, whereas fetal birth trauma may be mediated to a greater extent by
      large head size. Prenatal diagnosis of craniosynostosis could influence decision
      making in the management of labor. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

PMID- 26218397
TI  - Clinician-Graded Electronic Facial Paralysis Assessment: The eFACE.
AB  - BACKGROUND: The subjective nature of facial aesthetics and the difficulties
      associated with quantifying facial function have made outcomes analysis in facial
      paralysis challenging. Clinicians rely on photographs, subjective descriptions,
      and scales, limiting assessment, communication among providers, and communication
      between providers and patients. The authors describe the development and
      validation of a comprehensive, electronic, clinician-graded facial function scale
      (eFACE), which generates an overall disfigurement score and offers simple graphic
      output for clinician communication, assessment of various interventions, and
      patient understanding. The eFACE application may be used in a variety of
      electronic devices, including smartphones, tablets, and computers. METHODS: An
      instrument consisting of 16 items in a visual analogue scale format was developed
      to assess facial function and symmetry (the eFACE). Video recordings of subjects
      performing facial expressions were viewed, and the eFACE instrument was applied,
      along with an overall facial disfigurement score. A multiple regression analysis
      was performed to determine the best linear relationship between overall expert
      determined disfigurement and the eFACE items. The resulting equation was tested
      by three independent facial nerve clinicians, using an additional series of
      patients, to determine both interrater and intrarater reliability of the
      instrument. RESULTS: Multiple regression analysis produced good fit of eFACE
      parameters to overall expert-rated global facial disfigurement when dynamic
      parameters were weighted twice as heavily as static and synkinesis parameters.
      eFACE scores demonstrated very high interrater and intrarater reliability.
      CONCLUSION: The eFACE is a reliable, reproducible, and straightforward digital
      clinical measure with which to assess facial function and disfigurement in
      patients with facial paralysis.

PMID- 26218398
TI  - Motion Analysis for Microsurgical Training: Objective Measures of Dexterity,
      Economy of Movement, and Ability.
AB  - BACKGROUND: Evaluation of skill acquisition in microsurgery has traditionally
      relied on subjective opinions of senior faculty, but is shifting toward early
      competency-based training using validated models. No objective measures of
      dexterity, economy of movement, and ability exist. The authors propose a novel
      video instrument motion analysis scoring system to objectively measure motion.
      METHODS: Video of expert microsurgeons was analyzed and used to develop a
      resident motion analysis scoring system based on a mathematical model. Motion
      analysis scores were compared to blinded, global rating scores of the same videos
      using the Stanford Microsurgery and Resident Training scale. RESULTS: Eighty-five
      microsurgical anastomoses from 16 residents ranging from postgraduate years 1
      through 6 were analyzed. Composite motion analysis scores for each segmented
      video correlated positively to arterial anastomotic experience (rho, +0.77; p <
      0.001). Stanford Microsurgery and Resident Training scale interrater reliability
      was consistent between expert assessors, and mean composite motion analysis
      overall performance and Stanford scores were well matched for each level of
      experience. Composite motion analysis scores correlated significantly with
      combined Stanford Microsurgery and Resident Training [instrument handling (rho,
      +0.66; p < 0.01), efficiency (rho, +0.59; p < 0.01), suture handling (rho, +0.83;
      p < 0.001), operative flow (rho, +0.67; p < 0.001), and overall performance (rho,
      +89; p < 0.001)] motion components of the scale. CONCLUSIONS: Instrument motion
      analysis provides a novel, reliable, and consistent objective assessment for
      microsurgical trainees. It has an associated cost, but is timely, repeatable, and
      senior physician independent, and exposes patients to zero risk.

PMID- 26218399
TI  - Common Pediatric Congenital Conditions of the Hand.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Accurately diagnose congenital differences that affect the hand. 2.
      Develop a surgical plan for syndactyly with regard to timing of intervention to
      prevent progressive deformity and principles to restore the commissure. 3. List
      the potential complications following polydactyly reconstruction. 4. State the
      indications for pollicization for thumb hypoplasia. SUMMARY: Congenital
      conditions of the hand are commonly encountered in a pediatric hand surgery
      practice. The physician must be comfortable and have a sound understanding of the
      diagnosis and treatment algorithm. Certain diagnoses are inheritable and require
      genetic testing and/or genetic counseling. Appropriate referral is necessary to
      facilitate education about the congenital difference and its effect on subsequent
      generations. Syndactyly, polydactyly, thumb hypoplasia, and cleft hand are
      particularly commonplace and are discussed in this article. The treatment
      principles and surgical techniques are emphasized to maximize hand function and
      aesthetic outcome.

PMID- 26218400
TI  - Evidence-Based Education in Plastic Surgery.
AB  - Educational reforms in resident training have historically been driven by reports
      from medical societies and organizations. Although educational initiatives are
      well intended, they are rarely supported by robust evidence. The Accreditation
      Council for Graduate Medical Education recently introduced competency-based
      training, a form of outcomes-based education that has been used successfully in
      nonmedical professional vocations. This initiative has promise to advance the
      quality of resident education, but questions remain regarding implementation
      within plastic surgery. In particular, how will competency-based training impact
      patient outcomes, and will the methodologies used to assess competencies (i.e.,
      milestones) be accurate and validated by literature? This report investigates
      resident educational reform and the need for more evidence-based educational
      initiatives in plastic surgery training. 

PMID- 26218401
TI  - FACE-Q Scales for Health-Related Quality of Life, Early Life Impact, Satisfaction
      with Outcomes, and Decision to Have Treatment: Development and Validation.

PMID- 26218402
TI  - Reply: Medial Thigh Lift in the Massive Weight Loss Population: Outcomes and
      Complications.

PMID- 26218403
TI  - Resistance of the Lichen Buellia frigida to Simulated Space Conditions during the
      Preflight Tests for BIOMEX--Viability Assay and Morphological Stability.
AB  - Samples of the extremotolerant Antarctic endemite lichen Buellia frigida are
      currently exposed to low-Earth orbit-space and simulated Mars conditions at the
      Biology and Mars Experiment (BIOMEX), which is part of the ESA mission EXPOSE-R2
      on the International Space Station and was launched on 23 July 2014. In
      preparation for the mission, several preflight tests (Experimental and Scientific
      Verification Tests, EVT and SVT) assessed the sample preparation and hardware
      integration procedures as well as the resistance of the candidate organism toward
      the abiotic stressors experienced under space and Mars conditions. Therefore, we
      quantified the post-exposure viability with a live/dead staining technique
      utilizing FUN-1 and confocal laser scanning microscopy (CLSM). In addition, we
      used scanning electron microscopy (SEM) to investigate putative patterns of
      morphological-anatomical damage that lichens may suffer under the extreme
      exposure conditions. The present results demonstrate that Buellia frigida is
      capable of surviving the conditions tested in EVT and SVT. The mycobiont showed
      lower average impairment of its viability than the photobiont (viability rates of
      >83% and >69%, respectively), and the lichen thallus suffered no significant
      damage in terms of thalline integrity and symbiotic contact. These results will
      become essential to substantiate and validate the results prospectively obtained
      from the returning space mission. Moreover, they will help assess the limits and
      limitations of terrestrial organisms under space and Mars conditions as well as
      characterize the adaptive traits that confer lichen extremotolerance.

PMID- 26218404
TI  - Muckle-Wells syndrome: a rare hereditary cryopyrin-associated periodic syndrome.

PMID- 26218405
TI  - High Pressure Phase-Transformation Induced Texture Evolution and Strengthening in
      Zirconium Metal: Experiment and Modeling.
AB  - We studied the phase-transition induced texture changes and strengthening
      mechanism for zirconium metal under quasi-hydrostatic compression and uni-axial
      deformation under confined high pressure using the deformation-DIA (D-DIA)
      apparatus. It is shown that the experimentally obtained texture for omega-phase
      Zr can be qualitatively described by combining a subset of orientation variants
      previously proposed in two different models. The determined flow stress for the
      high-pressure omega-phase is 0.5-1.2 GPa, more than three times higher than that
      of the alpha-phase. Using first-principles calculations, we investigated the
      mechanical and electronic properties of the two Zr polymorphs. We find that the
      observed strengthening can be attributed to the relatively strong directional
      bonding in the omega phase, which significantly increases its shear plastic
      resistance over the alpha-phase Zr. The present findings provide an alternate
      route for Zr metal strengthening by high-pressure phase transformation. 

PMID- 26218406
TI  - Evaluation of postmortem drug concentrations in cerebrospinal fluid compared with
      blood and pericardial fluid.
AB  - In forensic toxicology, body fluids are important materials not only as
      alternatives to blood but also for investigation of postmortem drug
      redistributions and pharmaco-/toxicokinetic analysis; however, there are limited
      data on postmortem drug distributions in cerebrospinal fluid (CSF). The present
      study reviewed toxicological data of autopsy cases (n=103), in which drugs were
      detected in CSF using gas chromatography/mass spectrometry (GC/MS), to
      investigate drug concentrations in CSF, compared with blood and pericardial fluid
      (PCF) concentrations. Oral/injected amphetamines (n=23) showed similar CSF and
      blood/PCF concentrations with partly lower CSF concentrations (about *0.5-1.1).
      CSF concentrations of the venous anesthetic midazolam (n=7) were lower with poor
      correlations. Oral caffeine (n=15), acetaminophen (n=7), chlorpheniramine (n=6),
      dihydrocodeine (n=6), and phenobarbital (n=21) showed equivalent to lower CSF
      concentrations (about *0.2-1.2), compared with blood and PCF concentrations;
      however, CSF phenobarbital concentrations were high in a fatal intoxication case.
      CSF concentrations of phenothiazine derivatives (n=29) were markedly lower (about
      *0.1) than blood/PCF concentrations. The distribution of the local anesthetic
      lidocaine used in critical medical care (n=49) markedly varied by case. These
      findings suggest that CSF is useful in routine forensic toxicology as an
      alternative to blood as well as for investigating pharmaco-/toxicokinetics and
      postmortem redistributions. 

PMID- 26218407
TI  - Inflammatory responses to neutral fat and fatty acids in multiple organs in a rat
      model of fat embolism syndrome.
AB  - Fat embolism syndrome (FES) is a common complication of long bone fractures. FES
      is rare but with significant morbidity and occasional fatalities. Studies of
      animal models of FES are numerous; however, few studies compare inflammatory
      reactions in multiple organs. The present study investigated the effect of
      neutral fat and fatty acids, which cause changes in multiple organs and induce
      FES. Using rats we evaluated the ratio of lung-to-body weight and conducted
      histological analyses and quantitative analysis of inflammatory cytokine mRNAs in
      the lungs following intravenous administration of neutral fat or fatty acids.
      Neutral fat increased the ratio of lung-to-body weight, and neutral fat formed
      emboli in lung capillaries. The levels of interleukin-1 beta (IL-1beta), IL-6 and
      tumor necrosis factor-alpha (TNF-alpha) in the lungs increased after injection of
      neutral fat and oleic acid. Analysis of the histologic changes revealed that the
      highest numbers of fat droplets, occluding the capillaries of the lungs, kidney,
      heart, and brain formed 12h after the injection of neutral fat and fat droplets
      gradually diminished 48h later. Fat droplets were not detected in any organs
      after the injection of oleic acid. IL-1beta and TNF-alpha levels in the lungs
      were elevated 9-24h after the injection of neutral fat, although IL-6 levels
      peaked at 6h. After injection of oleic acid, peak levels of IL-1beta, IL-6, and
      TNF-alpha were detected at 6h, and IL-6 again increased in all organs and plasma
      at 15h. Neutral fat, but not fatty acids, formed emboli in the capillaries of
      multiple organs. These findings suggest that neutral fat increased inflammatory
      cytokine levels by forming emboli in organ capillaries, particularly in the
      lungs, while oleic acid augmented inflammatory cytokine levels by stimulating
      endothelial cells of multiple organs. 

PMID- 26218408
TI  - Growth pattern from birth to adulthood in African pygmies of known age.
AB  - The African pygmy phenotype stems from genetic foundations and is considered to
      be the product of a disturbance in the growth hormone-insulin-like growth factor
      (GH-IGF) axis. However, when and how the pygmy phenotype is acquired during
      growth remains unknown. Here we describe growth patterns in Baka pygmies based on
      two longitudinal studies of individuals of known age, from the time of birth to
      the age of 25 years. Body size at birth among the Baka is within standard limits,
      but their growth rate slows significantly during the first two years of life. It
      then more or less follows the standard pattern, with a growth spurt at
      adolescence. Their life history variables do not allow the Baka to be
      distinguished from other populations. Therefore, the pygmy phenotype in the Baka
      is the result of a change in growth that occurs during infancy, which
      differentiates them from East African pygmies revealing convergent evolution. 

PMID- 26218409
TI  - Implementation and Operational Research: Early Tracing of Children Lost to Follow
      Up From Antiretroviral Treatment: True Outcomes and Future Risks.
AB  - BACKGROUND: Loss to follow-up (LTFU) challenges the success of antiretroviral
      therapy (ART) scale-up among pediatric patients. Little is known about children
      who drop out of care. We aim to analyze risk factors for LTFU among children on
      ART, find their true outcomes through tracing, and investigate their final
      outcomes after resuming ART. METHODS: This is a descriptive, retrospective,
      cohort study of children on ART between April 2006 and December 2010 in 2 clinics
      in urban Malawi. Routine data from an electronic data system were used and
      matched with information obtained through routine tracing procedures. RESULTS: Of
      985 children (1999 child-years) on ART, 251 were LTFU: 12.6/100 child-years. At
      ART initiation, wasting [adjusted hazard ratio (AHR) 1.58 and 95% confidence
      interval (CI): 1.02 to 2.44] was independently associated with higher risk of
      LTFU. Of 201 LTFU children traced, 79% were found: 11% died, 25% stopped, 26%
      transferred-out, and 37% were still on ART. Median time between last visit and
      first tracing was 84 days (interquartile range: 64-101 days). Tracing reduced
      risk of LTFU by 38% (AHR 0.62 and 95% CI: 0.42 to 0.91) and decreased LTFU from
      23.2% to 8.5%. Additional outcomes of stop, death, and transfer-out increased 4.4
      fold, 1.8-fold, and 1.3-fold, respectively. Traced children with gaps in ART
      intake who resumed ART had higher risk of stopping (AHR 4.92 and 95% CI: 1.67 to
      14.5) and transfer out (AHR 2.70 and 95% CI: 1.75 to 4.17) as final outcome.
      CONCLUSIONS: Early tracing substantially reduces LTFU; approximately one-third
      presumed LTFU was found to be still on ART. Children with wasting at initiation
      and those traced and found to have irregular ART intake require targeted
      interventions.

PMID- 26218410
TI  - Impact of Illicit Drug Use on Health-Related Quality of Life in Opioid-Dependent
      Patients Undergoing HIV Treatment.
AB  - OBJECTIVE: To assess the impact of illicit drug use on health-related quality of
      life (health utility) among opioid-dependent HIV-infected patients. DESIGN:
      Secondary analyses of data from the Buprenorphine-HIV Evaluation and Support
      cohort of HIV-infected patients with opioid dependence in 9 US HIV clinics
      between 2004 and 2009. Health status [short form-12 (SF-12)], combination
      antiretroviral treatment (ART) status, CD4 cell count, hepatitis C virus antibody
      status, current drug use, and demographics were assessed at the initial visit and
      quarterly follow-up visits until 1 year. The SF-6D health utility scores were
      derived from the SF-12. Multivariate mixed-effects regression models were used to
      assess the impact of illicit drug use on health utility controlling for
      demographic, clinical, and social characteristics. RESULTS: Health utility was
      assessed among 307 participants, 67% male, with a median age of 46 years at 1089
      quarterly assessments. In multivariate analyses, illicit opioid use, nonopioid
      illicit drug use, not being on ART, and being on ART with poor adherence were
      associated with lower health utility. The observed decrement in health utility
      associated with illicit opioid use was larger for those on ART with good
      adherence (beta = -0.067; P < 0.01) or poor adherence (-0.049; P < 0.01) than for
      those not on ART. CONCLUSIONS: Illicit opioid and nonopioid drug use are
      negatively associated with health utility in patients with HIV; however, the
      relative effect of illicit opioid use is smaller than that of not being on ART.
      Postponing ART until initiation of opioid substitution therapy or abstinence may
      have limited benefits from the perspective of maximizing health utility.

PMID- 26218411
TI  - A Randomized Controlled Trial of Real-Time Electronic Adherence Monitoring With
      Text Message Dosing Reminders in People Starting First-Line Antiretroviral
      Therapy.
AB  - BACKGROUND: There are conflicting findings about whether mobile phone text
      message reminders impact on antiretroviral adherence. We hypothesized that text
      reminders sent when dosing was late would improve adherence and HIV viral
      suppression. METHODS: Antiretroviral therapy (ART)-naive participants, from a
      South African outpatient ART clinic, were randomized to standard of care (SoC, 3
      pretreatment education sessions), or intervention (SoC and automated text
      reminders if dosing >30 minutes late). Dosing time was recorded by real-time
      electronic adherence monitoring devices, given to participants at ART start. CD4
      cell count and HIV RNA were determined at baseline, 16 and 48 weeks. Primary
      outcome was cumulative adherence execution by electronic adherence monitoring
      device. HIV-1 viral suppression (<40 copies/mL) at week 48 and count of treatment
      interruptions (TIs) >72 hours were secondary outcomes. Analysis was by intention
      to treat (missing = failure). Registration was with the Pan-African Clinical
      Trials Registry: PACTR201311000641402. RESULTS: A total of 230 participants were
      randomly assigned to control (n = 115) or intervention (n = 115) arms. Median
      adherence was 82.1% (interquartile range, 56.6%-94.6%) in the intervention arm,
      compared with 80.4% (interquartile range, 52.8%-93.8%) for SoC [adjusted odds
      ratio for adherence 1.08; 95% confidence interval (CI): 0.77 to 1.52]. Suppressed
      HIV RNA (<40 copies/mL) occurred in 80 (69.6%) of control and 75 (65.2%) of
      intervention (adjusted odds ratio for virological failure in intervention arm
      0.77; 95% CI: 0.42 to 1.40). In the intervention arm, the count of TIs of >72
      hours was reduced (adjusted incident rate ratio, 0.84; 95% CI: 0.75 to 0.94).
      CONCLUSIONS: Text message reminders linked to late doses detected by real-time
      adherence monitoring reduced the number of prolonged TIs, but did not
      significantly improve adherence or viral suppression.

PMID- 26218412
TI  - Authors' Reply: Early Initiation of Antiretroviral Therapy Among Young Children:
      A Long Way to Go.

PMID- 26218413
TI  - Authors' Reply: Nutritional Support to HIV Patients Starting ART.

PMID- 26218414
TI  - Oncologic and Functional Outcomes of Laparoendoscopic Single-Site Radical
      Nephrectomy for Localized Kidney Cancer: A Single Surgeon's Series with a Minimum
      of 3-Year Follow-Up.
AB  - OBJECTIVE: To evaluate intermediate-term oncologic and renal functional outcome
      of laparoendoscopic single-site radical nephrectomy (LESS-RN) in the treatment of
      localized kidney cancer. METHODS: We performed a chart review of patients who
      underwent LESS-RN between 2009 and 2011 at our institution. Patients with a
      minimum of 3 years of follow-up were included in this study. The demographic data
      and main perioperative outcome variables were analyzed. Estimated glomerular
      filtration rate was calculated using the Modification of Diet Renal Disease
      equation. Upstaging of chronic kidney disease (CKD) was calculated. The Kaplan
      Meier method was used to calculate overall survival (OS), cancer-specific
      survival (CSS), and cancer-free survival (CFS). Multivariate logistic regression
      was performed to show predicting factors for an undesirable outcome arbitrarily
      defined as any one or more of the following events: surgical conversion,
      complication of Clavien grade >2, new onset of CKD stages >=3 at the latest
      follow-up, or cancer recurrence or metastasis. RESULTS: A total of 51 patients
      were included with a median follow-up of 41 (interquartile range: 38-45) months.
      The OS, CSS, and CFS rates at 3 years were 100%, 100%, and 98%, respectively.
      There was a 74.5% (38/51) upstaging of CKD at the latest follow-up, with 22
      patients (43.1%) who developed a new onset of CKD stages >=3. Multivariate
      analysis showed that patient age, body mass index, Charlson comorbidity index,
      early surgeon experience, and follow-up duration (all p < 0.05) have increased
      the odds of an undesirable outcome. CONCLUSIONS: For localized kidney cancer,
      LESS-RN is effective in oncologic control at an intermediate follow-up interval
      but, similar to other kinds of RN technique, it is associated with worsened renal
      functional outcomes.

PMID- 26218415
TI  - Atherogenic lipids and macrophage subsets.
AB  - PURPOSE OF REVIEW: Macrophage foam cells are important cells in the vascular wall
      that contribute to the inflammation associated with atherosclerotic lesions.
      Recent studies have demonstrated the heterogeneity of macrophages in lesions. In
      this review, advances in our understanding of the formation of foam cells by
      macrophage subsets in atherosclerotic plaques will be discussed. RECENT FINDINGS:
      Macrophage subsets develop in response to the microenvironment in the arterial
      wall. The uptake of lipoproteins, particularly oxidized LDL, has been considered
      the major mechanism of foam cell formation. However, native and aggregated LDL
      can also be taken up by macrophages and M2 macrophages have been shown to be
      efficient in the uptake of apoptotic cells that can contribute lipids to the
      cells. The ability of the macrophage subsets to respond to bioactive lipids in
      the artery wall to either promote macrophage subset polarization and/or to
      promote foam cell formation is only beginning to be understood. SUMMARY: Although
      we are beginning to appreciate the heterogeneity of macrophages present in
      atherosclerotic plaques, further work is required to fully understand the
      molecular basis for the differential ability of macrophage subsets to form foam
      cells and to respond to bioactive lipids.

PMID- 26218417
TI  - Endothelial and smooth muscle cell transformation in atherosclerosis.
AB  - PURPOSE OF REVIEW: Physiologically, endothelial integrity and smooth muscle
      homeostasis play key roles in the maintenance of vascular structure and
      functions. Under pathological conditions, endothelial and smooth muscle cells
      display great plasticity by transdifferentiating into other cell phenotypes. This
      review aims to update the progress in endothelial and smooth muscle cell
      transformation and to discuss their underlying mechanisms. RECENT FINDINGS: At
      the early stage of atherosclerosis, it was traditionally believed that smooth
      muscle cells from the media migrate into the intima in which they proliferate to
      form neointimal lesions. Recently, endothelial cells were shown to undergo
      transformation to form smooth muscle-like cells that contribute to neointimal
      formation. Furthermore, not only can medial smooth muscle cells migrate and
      proliferate, they also have the ability to differentiate into macrophages in the
      intima in which they form foam cells by uptaking lipids. Finally, the discovery
      of stem/progenitor cells in the vessel wall that can differentiate into all types
      of vascular cells has complicated the research field even further. SUMMARY: Based
      on the current progress in the research field, it is worthy to explore the
      contributions of cell transformation to the pathogenesis of atherosclerosis to
      understand the mechanisms on how they are regulated in order to develop novel
      therapeutic application targeting these processes to reverse the disease
      progression.

PMID- 26218416
TI  - Blood flow modulation of vascular dynamics.
AB  - PURPOSE OF REVIEW: Blood flow is intimately linked with cardiovascular
      development, repair and dysfunction. The current review will build on the fluid
      mechanical principle underlying haemodynamic shear forces, mechanotransduction
      and metabolic effects. RECENT FINDINGS: Pulsatile flow produces both time
      (?tau/?t) and spatial-varying shear stress (?tau/?x) to modulate vascular
      oxidative stress and inflammatory response with pathophysiological significance
      to atherosclerosis. The characteristics of haemodynamic shear forces, namely,
      steady laminar (?tau/?t = 0), pulsatile shear stress (PSS: unidirectional forward
      flow) and oscillatory shear stress (bidirectional with a near net 0 forward
      flow), modulate mechano-signal transduction to influence metabolic effects on
      vascular endothelial function. Atheroprotective PSS promotes antioxidant, anti
      inflammatory and antithrombotic responses, whereas atherogenic oscillatory shear
      stress induces nicotinamide adenine dinucleotide phosphate oxidase-JNK signalling
      to increase mitochondrial superoxide production, protein degradation of manganese
      superoxide dismutase and post-translational protein modifications of LDL
      particles in the disturbed flow-exposed regions of vasculature. In the era of
      tissue regeneration, shear stress has been implicated in reactivation of
      developmental genes, namely, Wnt and Notch signalling, for vascular development
      and repair. SUMMARY: Blood flow imparts a dynamic continuum from vascular
      development to repair. Augmentation of PSS confers atheroprotection and
      reactivation of developmental signalling pathways for regeneration.

PMID- 26218418
TI  - Emerging roles of flavin monooxygenase 3 in cholesterol metabolism and
      atherosclerosis.
AB  - PURPOSE OF REVIEW: Atherosclerosis and associated cardiovascular disease still
      remain the largest cause of mortality worldwide. Several recent studies have
      discovered that metabolism of common nutrients by gut microbes can produce a
      proatherogenic metabolite called trimethylamine-N-oxide (TMAO). The goal of this
      review is to discuss emerging evidence that the hepatic enzyme that generates
      TMAO, flavin monooxygenase 3 (FMO3), plays a regulatory role in maintaining whole
      body cholesterol balance and atherosclerosis development. RECENT FINDINGS:
      Several independent studies have recently uncovered a link between either FMO3
      itself or its enzymatic product TMAO with atherosclerosis and hepatic insulin
      resistance. These recent studies show that inhibition of FMO3 stimulates
      macrophage reverse cholesterol transport and protects against atherosclerosis in
      mice. SUMMARY: A growing body of work demonstrates that nutrients present in high
      fat foods (phosphatidylcholine, choline and L-carnitine) can be metabolized by
      the gut microbial enzymes to generate trimethylamine, which is then further
      metabolized by the host enzyme FMO3 to produce proatherogenic TMAO. Here, we
      discuss emerging evidence that the TMAO-producing enzyme FMO3 is centrally
      involved in the pathogenesis of atherosclerosis by regulating cholesterol
      metabolism and insulin resistance, and how these new insights provide exciting
      new avenues for cardiovascular disease therapies.

PMID- 26218420
TI  - Electrostatic coupling between DNA and its counterions modulates the observed
      translational diffusion coefficients.
AB  - Free solution capillary electrophoresis (CE) is a useful technique for measuring
      the translational diffusion coefficients of charged analytes. The measurements
      are relatively fast if the polarity of the electric field is reversed to drive
      the analyte back and forth past the detection window during each run. We have
      tested the validity of the resulting diffusion coefficients using double-stranded
      DNA molecules ranging in size from 20 to 960 base pairs as the model system. The
      diffusion coefficients of small DNAs are equal to values in the literature
      measured by other techniques. However, the diffusion coefficients of DNA
      molecules larger than ~30 base pairs are anomalously high and deviate
      increasingly from the literature values with increasing DNA molar mass. The
      anomalously high diffusion coefficients are due to electrostatic coupling between
      the DNA and its counterions. As a result, the measured diffusion coefficients
      vary with the diffusion coefficient of the counterion, as well as with cation
      concentration and electric field strength. These effects can be reduced or
      eliminated by measuring apparent diffusion coefficients of the DNA at several
      different electric field strengths and extrapolating the results to zero electric
      field. 

PMID- 26218419
TI  - What does procollagen C-endopeptidase enhancer protein 2 have to do with HDL
      cholesteryl ester uptake? Or how I learned to stop worrying and love reverse
      cholesterol transport?
AB  - PURPOSE OF REVIEW: The purpose of this study is to provide an update on the role
      HDL apolipoprotein A-I plays in reducing the risk of cardiovascular disease (CVD)
      and how it relates to reverse cholesterol transport (RCT). RECENT FINDINGS:
      Despite numerous studies showing that plasma HDL cholesterol concentrations are
      correlated with a reduced risk of CVD, pharmacologic elevation of HDL has not
      shown any beneficial effects to date. In contrast, studies correlating the
      measure of an individual's plasma cholesterol efflux capacity show greater
      promise as a tool for assessing CVD risk. Although ATP-binding cassette
      transporter 1-mediated lipidation of apoA-I is considered the principal source of
      plasma HDL, it represents only one side of the RCT pathway. Equally important is
      the second half of the RCT pathway in which the liver scavenger receptor class B1
      selectively removes HDL cholesteryl esters for excretion. The combined action of
      the two enzyme systems is reflected in the overall steady-state concentration of
      plasma HDL cholesterol. For example, reduced ATP-binding cassette transporter 1
      mediated production of nascent HDL lowers plasma HDL concentration, just as an
      increase in cholesteryl ester uptake by scavenger receptor class B1 reduces HDL
      levels. Thus, the complexity of intravascular HDL metabolism suggests that steady
      state plasma HDL concentrations do not provide adequate information regarding an
      individual's HDL quality or function. Herein, we describe a new player,
      procollagen C-endopeptidase enhancer 2, which shows atheroprotective function and
      influences both sides of RCT by enhancing production and catabolism of HDL
      cholesteryl esters. SUMMARY: The discovery of a new molecule, procollagen C
      endopeptidase enhancer 2, implicated in the regulation of HDL cholesteryl ester
      concentrations suggests that the extracellular matrix and the proteins that
      regulate its function represent a new and as yet unexplored realm of HDL
      cholesterol metabolism.

PMID- 26218421
TI  - CSB-PGBD3 Mutations Cause Premature Ovarian Failure.
AB  - Premature ovarian failure (POF) is a rare, heterogeneous disorder characterized
      by cessation of menstruation occurring before the age of 40 years. Genetic
      etiology is responsible for perhaps 25% of cases, but most cases are sporadic and
      unexplained. In this study, through whole exome sequencing in a non
      consanguineous family having four affected members with POF and Sanger sequencing
      in 432 sporadic cases, we identified three novel mutations in the fusion gene CSB
      PGBD3. Subsequently functional studies suggest that mutated CSB-PGBD3 fusion
      protein was impaired in response to DNA damage, as indicated by delayed or absent
      recruitment to damaged sites. Our data provide the first evidence that mutations
      in the CSB-PGBD3 fusion protein can cause human disease, even in the presence of
      functional CSB, thus potentially explaining conservation of the fusion protein
      for 43 My since marmoset. The localization of the CSB-PGBD3 fusion protein to UVA
      induced nuclear DNA repair foci further suggests that the CSB-PGBD3 fusion
      protein, like many other proteins that can cause POF, modulates or participates
      in DNA repair. 

PMID- 26218422
TI  - The Side-Effect Effect in Children Is Robust and Not Specific to the Moral Status
      of Action Effects.
AB  - Adults' intentionality judgments regarding an action are influenced by their
      moral evaluation of this action. This is clearly indicated in the so-called side
      effect effect: when told about an action (e.g. implementing a business plan) with
      an intended primary effect (e.g. raise profits) and a foreseen side effect (e.g.
      harming/helping the environment), subjects tend to interpret the bringing about
      of the side effect more often as intentional when it is negative (harming the
      environment) than when it is positive (helping the environment). From a cognitive
      point of view, it is unclear whether the side-effect effect is driven by the
      moral status of the side effects specifically, or rather more generally by its
      normative status. And from a developmental point of view, little is known about
      the ontogenetic origins of the effect. The present study therefore explored the
      cognitive foundations and the ontogenetic origins of the side-effect effect by
      testing 4-to 5-year-old children with scenarios in which a side effect was in
      accordance with/violated a norm. Crucially, the status of the norm was varied to
      be conventional or moral. Children rated the bringing about of side-effects as
      more intentional when it broke a norm than when it accorded with a norm
      irrespective of the type of norm. The side-effect effect is thus an early
      developing, more general and pervasive phenomenon, not restricted to morally
      relevant side effects. 

PMID- 26218423
TI  - Three New Pierce's Disease Pathogenicity Effectors Identified Using Xylella
      fastidiosa Biocontrol Strain EB92-1.
AB  - Xylella fastidiosa (X. fastidiosa) infects a wide range of plant hosts and causes
      economically serious diseases, including Pierce's Disease (PD) of grapevines. X.
      fastidiosa biocontrol strain EB92-1 was isolated from elderberry and is
      infectious and persistent in grapevines but causes only very slight symptoms
      under ideal conditions. The draft genome of EB92-1 revealed that it appeared to
      be missing genes encoding 10 potential PD pathogenicity effectors found in
      Temecula1. Subsequent PCR and sequencing analyses confirmed that EB92-1 was
      missing the following predicted effectors found in Temecula1: two type II
      secreted enzymes, including a lipase (LipA; PD1703) and a serine protease
      (PD0956); two identical genes encoding proteins similar to Zonula occludens
      toxins (Zot; PD0915 and PD0928), and at least one relatively short, hemagglutinin
      like protein (PD0986). Leaves of tobacco and citrus inoculated with cell-free,
      crude protein extracts of E. coli BL21(DE3) overexpressing PD1703 exhibited a
      hypersensitive response (HR) in less than 24 hours. When cloned into shuttle
      vector pBBR1MCS-5, PD1703 conferred strong secreted lipase activity to
      Xanthomonas citri, E. coli and X. fastidiosa EB92-1 in plate assays. EB92
      1/PD1703 transformants also showed significantly increased disease symptoms on
      grapevines, characteristic of PD. Genes predicted to encode PD0928 (Zot) and a
      PD0986 (hemagglutinin) were also cloned into pBBR1MCS-5 and moved into EB92-1;
      both transformants also showed significantly increased symptoms on V. vinifera
      vines, characteristic of PD. Together, these results reveal that PD effectors
      include at least a lipase, two Zot-like toxins and a possibly redundant
      hemagglutinin, none of which are necessary for parasitic survival of X.
      fastidiosa populations in grapevines or elderberry. 

PMID- 26218424
TI  - Neural substrates of child irritability in typically developing and psychiatric
      populations.
AB  - Irritability is an aspect of the negative affectivity domain of temperament, but
      in severe and dysregulated forms is a symptom of a range of psychopathologies.
      Better understanding of the neural underpinnings of irritability, outside the
      context of specific disorders, can help to understand normative variation but
      also characterize its clinical salience in psychopathology diagnosis. This study
      assessed brain activation during reward and frustration, domains of behavioral
      deficits in childhood irritability. Children (age 6-9) presenting in mental
      health clinics for extreme and impairing irritability (n = 26) were compared to
      healthy children (n = 28). Using developmentally sensitive methods, neural
      activation was measured via a negative mood induction paradigm during fMRI
      scanning. The clinical group displayed more activation of the anterior cingulate
      and middle frontal gyrus during reward, but less activation during frustration,
      than healthy comparison children. The opposite pattern was found in the posterior
      cingulate. Further, in clinical subjects, parent report of irritability was
      dimensionally related to decreased activation of the anterior cingulate and
      striatum during frustration. The results of this study indicate neural
      dysfunction within brain regions related to reward processing, error monitoring,
      and emotion regulation underlying clinically impairing irritability. Results are
      discussed in the context of a growing field of neuroimaging research
      investigating irritable children.

PMID- 26218425
TI  - The Contribution of Normal Pregnancy to Eclampsia.
AB  - Eclampsia, clinically defined as unexplained seizure in a woman with
      preeclampsia, is a life threatening complication unique to the pregnant state.
      However, a subpopulation of women with seemingly uncomplicated pregnancies
      experience de novo seizure without preeclamptic signs or symptoms, suggesting
      pregnancy alone may predispose the brain to seizure. Here, we hypothesized that
      normal pregnancy lowers seizure threshold and investigated mechanisms by which
      pregnancy may affect seizure susceptibility, including neuroinflammation and
      plasticity of gamma-aminobutyric acid type A receptor (GABAAR) subunit
      expression. Seizure threshold was determined by quantifying the amount of
      pentylenetetrazole (PTZ) required to elicit electrical seizure in Sprague Dawley
      rats that were either nonpregnant (Nonpreg, n = 7) or pregnant (Preg; d20, n =
      6). Seizure-induced vasogenic edema was also measured. Further, activation of
      microglia, a measure of neuroinflammation (n = 6-8/group), and GABAAR delta- and
      gamma2-subunit protein expression in the cerebral cortex and hippocampus (n =
      6/group) was determined. Seizure threshold was lower in Preg compared to Nonpreg
      rats (36.7+/-9.6 vs. 65.0+/-14.5 mg/kg PTZ; p<0.01) that was associated with
      greater vasogenic edema formation (78.55+/-0.11 vs. 78.04+/-0.19% water; p<0.05).
      The % of active microglia was similar between groups; however, pregnancy was
      associated with downregulation of cortical GABAAR-delta and hippocampal GABAAR
      gamma2 expression. Overall, pregnancy appears to be a state of increased seizure
      susceptibility that is not due to neuroinflammation, but rather is associated
      with reduced expression of GABAAR subunits and greater edema. Understanding
      neurophysiological changes occurring in normal pregnancy could allow for better
      prevention and management of de novo seizure, including pathologic states such as
      eclampsia. 

PMID- 26218426
TI  - Expression and Subcellular Distribution of GFP-Tagged Human Tetraspanin Proteins
      in Saccharomyces cerevisiae.
AB  - Tetraspanins are integral membrane proteins that function as organizers of
      multimolecular complexes and modulate function of associated proteins. Mammalian
      genomes encode approximately 30 different members of this family and remotely
      related eukaryotic species also contain conserved tetraspanin homologs.
      Tetraspanins are involved in a number of fundamental processes such as regulation
      of cell migration, fusion, immunity and signaling. Moreover, they are implied in
      numerous pathological states including mental disorders, infectious diseases or
      cancer. Despite the great interest in tetraspanins, the structural and
      biochemical basis of their activity is still largely unknown. A major bottleneck
      lies in the difficulty of obtaining stable and homogeneous protein samples in
      large quantities. Here we report expression screening of 15 members of the human
      tetraspanin superfamily and successful protocols for the production in S.
      cerevisiae of a subset of tetraspanins involved in human cancer development. We
      have demonstrated the subcellular localization of overexpressed tetraspanin-green
      fluorescent protein fusion proteins in S. cerevisiae and found that despite being
      mislocalized, the fusion proteins are not degraded. The recombinantly produced
      tetraspanins are dispersed within the endoplasmic reticulum membranes or
      localized in granule-like structures in yeast cells. The recombinantly produced
      tetraspanins can be extracted from the membrane fraction and purified with
      detergents or the poly (styrene-co-maleic acid) polymer technique for use in
      further biochemical or biophysical studies. 

PMID- 26218427
TI  - Integrative rehabilitation of residents chronic post-stroke in skilled nursing
      facilities: the design and evaluation of the BrightArm Duo.
AB  - PURPOSE: To describe the novel BrightArm Duo bimanual upper extremity (UE)
      rehabilitation system; to determine its technology acceptance and clinical
      benefit for older hemiplegic participants. METHODS: The system table tilted to
      adjust arm gravity loading. Participants wore arm supports that sensed grasp
      strength and wrist position on the table. Wrist weights further increased
      shoulder exertion. Games were designed to improve UE strength, motor function,
      cognition and emotive state and adapted automatically to each participant. The
      system underwent feasibility trials spanning 8 weeks in two skilled nursing
      facilities (SNFs). Participants were evaluated pre-therapy and post-therapy using
      standardized clinical measures. Computerized measures of supported arm reach,
      table tilt and number of arm repetitions were stored on a remote server.
      OUTCOMES: Seven participants had significant improvements in their active range
      of shoulder movement, supported arm reach, shoulder strength, grasp strength and
      their ability to focus. The group demonstrated higher arm function measured with
      FMA (p = 0.01) and CAHAI (p = 0.05), and had an improvement in depression (Becks
      Depression Inventory, II). BrightArm Duo technology was well accepted by
      participants with a rating of 4.4 out of 5 points. CONCLUSIONS: Given these
      findings, it will be beneficial to evaluate the BrightArm Duo application in SNF
      maintenance programs. Implications for Rehabilitation Integrative rehabilitation
      that addresses both physical and cognitive domains is promising for post-stroke
      maintenance in skilled nursing facilities. Simultaneous bilateral arm exercise
      may improve arm function in older hemiplegic patients several years after stroke.
      Virtual reality games that adapt to the patient can increase attention and
      working memory while decreasing depression in elderly.

PMID- 26218428
TI  - Inactivation of ca10a and ca10b Genes Leads to Abnormal Embryonic Development and
      Alters Movement Pattern in Zebrafish.
AB  - Carbonic anhydrase related proteins (CARPs) X and XI are highly conserved across
      species and are predominantly expressed in neural tissues. The biological role of
      these proteins is still an enigma. Ray-finned fish have lost the CA11 gene, but
      instead possess two co-orthologs of CA10. We analyzed the expression pattern of
      zebrafish ca10a and ca10b genes during embryonic development and in different
      adult tissues, and studied 61 CARP X/XI-like sequences to evaluate their
      phylogenetic relationship. Sequence analysis of zebrafish ca10a and ca10b reveals
      strongly predicted signal peptides, N-glycosylation sites, and a potential
      disulfide, all of which are conserved, suggesting that all of CARP X and XI are
      secretory proteins and potentially dimeric. RT-qPCR showed that zebrafish ca10a
      and ca10b genes are expressed in the brain and several other tissues throughout
      the development of zebrafish. Antisense morpholino mediated knockdown of ca10a
      and ca10b showed developmental delay with a high rate of mortality in larvae.
      Zebrafish morphants showed curved body, pericardial edema, and abnormalities in
      the head and eye, and there was increased apoptotic cell death in the brain
      region. Swim pattern showed abnormal movement in morphant zebrafish larvae
      compared to the wild type larvae. The developmental phenotypes of the ca10a and
      ca10b morphants were confirmed by inactivating these genes with the CRISPR/Cas9
      system. In conclusion, we introduce a novel zebrafish model to investigate the
      mechanisms of CARP Xa and CARP Xb functions. Our data indicate that CARP Xa and
      CARP Xb have important roles in zebrafish development and suppression of ca10a
      and ca10b expression in zebrafish larvae leads to a movement disorder. 

PMID- 26218429
TI  - Opposing Effects of cAMP and T259 Phosphorylation on Plasma Membrane Diffusion of
      the Water Channel Aquaporin-5 in Madin-Darby Canine Kidney Cells.
AB  - Aquaporin-5 (AQP5) facilitates passive water transport in glandular epithelia in
      response to secretory stimuli via intracellular pathways involving calcium
      release, cAMP and protein kinase A (PKA). In epithelial plasma membranes, AQP5
      may be acutely regulated to facilitate water transport in response to
      physiological stimuli by changes in protein modifications, interactions with
      proteins and lipids, nanoscale membrane domain organization, and turnover rates.
      Such regulatory mechanisms could potentially be associated with alteration of
      diffusion behavior, possibly resulting in a change in the plasma membrane
      diffusion coefficient of AQP5. We aimed to test the short-term regulatory effects
      of the above pathways, by measuring lateral diffusion of AQP5 and an AQP5 phospho
      mutant, T259A, using k-space Image Correlation Spectroscopy of quantum dot- and
      EGFP-labeled AQP5. Elevated cAMP and PKA inhibition significantly decreased
      lateral diffusion of AQP5, whereas T259A mutation showed opposing effects;
      slowing diffusion without stimulation and increasing diffusion to basal levels
      after cAMP elevation. Thus, lateral diffusion of AQP5 is significantly regulated
      by cAMP, PKA, and T259 phosphorylation, which could be important for regulating
      water flow in glandular secretions. 

PMID- 26218430
TI  - Effects of Switching Behavior for the Attraction on Pedestrian Dynamics.
AB  - Walking is a fundamental activity of our daily life not only for moving to other
      places but also for interacting with surrounding environment. While walking on
      the streets, pedestrians can be aware of attractions like shopping windows. They
      can be influenced by the attractions and some of them might shift their attention
      towards the attractions, namely switching behavior. As a first step to
      incorporate the switching behavior, this study investigates collective effects of
      switching behavior for an attraction by developing a behavioral model. Numerical
      simulations exhibit different patterns of pedestrian behavior depending on the
      strength of the social influence and the average length of stay. When the social
      influence is strong along with a long length of stay, a saturated phase can be
      defined at which all the pedestrians have visited the attraction. If the social
      influence is not strong enough, an unsaturated phase appears where one can
      observe that some pedestrians head for the attraction while others walk in their
      desired direction. These collective patterns of pedestrian behavior are
      summarized in a phase diagram by comparing the number of pedestrians who visited
      the attraction to the number of passersby near the attraction. Measuring the
      marginal benefits with respect to the strength of the social influence and the
      average length of stay enables us to identify under what conditions enhancing
      these variables would be more effective. The findings from this study can be
      understood in the context of the pedestrian facility management, for instance,
      for retail stores. 

PMID- 26218432
TI  - Correction: Misunderstanding of Front-Of-Package Nutrition Information on US Food
      Products.

PMID- 26218431
TI  - The Neural Basis of Typewriting: A Functional MRI Study.
AB  - To investigate the neural substrate of typewriting Japanese words and to detect
      the difference between the neural substrate of typewriting and handwriting, we
      conducted a functional magnetic resonance imaging (fMRI) study in 16 healthy
      volunteers. All subjects were skillful touch typists and performed five tasks: a
      typing task, a writing task, a reading task, and two control tasks. Three brain
      regions were activated during both the typing and the writing tasks: the left
      superior parietal lobule, the left supramarginal gyrus, and the left premotor
      cortex close to Exner's area. Although typing and writing involved common brain
      regions, direct comparison between the typing and the writing task revealed
      greater left posteromedial intraparietal cortex activation in the typing task. In
      addition, activity in the left premotor cortex was more rostral in the typing
      task than in the writing task. These findings suggest that, although the brain
      circuits involved in Japanese typewriting are almost the same as those involved
      in handwriting, there are brain regions that are specific for typewriting. 

PMID- 26218433
TI  - Environmental Conditions Affect Botrytis cinerea Infection of Mature Grape
      Berries More Than the Strain or Transposon Genotype.
AB  - Effects of environment, Botrytis cinerea strain, and their interaction on the
      infection of mature grape berries were investigated. The combined effect of
      temperature (T) of 15, 20, 25, and 30 degrees C and relative humidity (RH) of 65,
      80, 90, and 100% was studied by inoculating berries with mycelium plugs.
      Regardless of the T, no disease occurred at 65% RH, and both disease incidence
      and severity increased with increasing RH. The combined effect of T (5 to 30
      degrees C) and wetness duration (WD) of 3, 6, 12, 24, and 36 h was studied by
      inoculating berries with conidia. At WD of 36 h, disease incidence was
      approximately 75% of affected berries at 20 or 25 degrees C, 50% at 15 degrees C,
      and 30 to 20% at 30 and 10 degrees C; no infection occurred at 5 degrees C. Under
      favorable conditions (100% RH or 36 h of WD) and unfavorable conditions (65% RH
      or 3 h of WD), berry wounding did not significantly affect disease incidence;
      under moderately favorable conditions (80% RH or 6 to 12 h of WD), disease
      incidence was approximately 1.5 to 5 times higher in wounded than in intact
      berries. Our data collectively showed that (i) T and RH or WD were more important
      than strain for mature berry infection by either mycelium or conidia and (ii) the
      effect of the environment on the different strains was similar. Two equations
      were developed describing the combined effect of T and RH, or T and WD, on
      disease incidence following inoculation by mycelium (R2=0.99) or conidia
      (R2=0.96), respectively. These equations may be useful in the development of
      models used to predict and control Botrytis bunch rot during berry ripening.

PMID- 26218434
TI  - Tetranuclear and Pentanuclear Compounds of the Rare-Earth Metals: Synthesis and
      Magnetism.
AB  - The Schiff-base proligand 4-tert-butyl-2,6-bis-[(2-hydroxy
      phenylimino)methyl]phenol (H3L) was prepared in situ from 4-tert-butyl-2,6
      diformylphenol and 2-aminophenol. The proligand (H3L) was used with
      dibenzoylmethane (DBMH) or acetylacetone (acacH) with lanthanides giving
      compounds with varying arrangements of metal atoms and nuclearities. The
      tetranuclear compound {[Dy4(L)3(DBM)4][Et3NH]} (1) and pentanuclear compound
      {[Dy5(MU3-OH)2(L)3(DBM)4(MeOH)4].4(MeOH)} (2) were obtained from the ligand (L)(3
      ) and dibenzoylmethane. The tetranuclear compounds {[Dy4(MU4
      OH)(L)2(acac)4(MeOH)2(EtOH)(H2O)].(NO3).2(MeOH).3(EtOH)} (3) and {[Ln4(MU3
      OH)2(L)(HL)(acac)5(H2O)] (HNEt3)(NO3).2(Et2O)} (Ln = Tb (4), Dy (5), Ho (6), and
      Tm (7)) resulted when the ligand (L)(3-) was used in the presence of
      acetylacetone. In the solid state structures, the tetranuclear compound 1 adopts
      a linear arrangement of metal atoms, while tetranuclear compound 3 has a square
      grid arrangement of metal atoms, and tetranuclear compounds 4-7 have a seesaw
      shaped arrangement of metal atoms. The composition found from single-crystal X
      ray analysis of compound 1 and 3-7 is supported by electrospray ionization mass
      spectrometry (ESI-MS). The magnetic studies on compounds 1 suggest the presence
      of weak ferromagnetic interactions, whereas compounds 2-6 exhibit weak
      antiferromagnetic interactions between neighboring metal centers. Compounds 1, 2,
      and 3 also show single-molecule magnet behavior under an applied dc field. 

PMID- 26218435
TI  - A longitudinal investigation of the relationship between maternal mind-mindedness
      and theory of mind.
AB  - Data are presented from a longitudinal investigation examining the relationship
      between maternal mind-mindedness (MM) in infancy and socio-cognitive development
      in childhood. We revisited children (n = 18) who had taken part in a longitudinal
      study as infants. MM had been assessed at 10, 12, 16, and 20 months of age. We
      followed up these children at 5-6 years of age to test their higher order theory
      of mind (ToM) (using the strange stories task). The convergent validity, temporal
      stability, and predictive validity of the construct of MM were examined in a
      longitudinal data set. The five measures of MM were not significantly correlated.
      Mother's production of appropriate mind-related comments (but no other measures)
      showed evidence of temporal stability throughout infancy. Thus, MM (as measured
      by appropriate mind-related comments) was confirmed as a stable construct.
      Children's ToM at 5-6 years of age was significantly predicted by their mother's
      MM up to 4 years earlier, with MM accounting for 40% of the variance of the
      strange stories task scores. These findings identify a relationship between MM
      across a protracted period of infancy and socio-cognitive development at 5-6
      years of age. 

PMID- 26218436
TI  - Correction: Silencing of Cholinergic Basal Forebrain Neurons Using
      Archaerhodopsin Prolongs Slow-Wave Sleep in Mice.

PMID- 26218437
TI  - Sustained Inhibition of Proliferative Response After Transient FGF Stimulation Is
      Mediated by Interleukin 1 Signaling.
AB  - Transient FGF stimulation of various cell types results in FGF memory--a
      sustained blockage of efficient proliferative response to FGF and other growth
      factors. FGF memory establishment requires HDAC activity, indicating its
      epigenetic character. FGF treatment stimulates proinflammatory NFkappaB
      signaling, which is also critical for FGF memory formation. The search for FGF
      induced mediators of FGF memory revealed that FGF stimulates HDAC-dependent
      expression of the inflammatory cytokine IL1alpha. Similarly to FGF, transient
      cell treatment with recombinant IL1alpha inhibits the proliferative response to
      further FGF and EGF stimulation, but does not prevent FGF receptor-mediated
      signaling. Interestingly, like cells pretreated with FGF1, cells pretreated with
      IL1alpha exhibit enhanced restructuring of actin cytoskeleton and increased
      migration in response to FGF stimulation. IRAP, a specific inhibitor of IL 1
      receptor, and a neutralizing anti-IL1alpha antibody prevent the formation of FGF
      memory and rescue an efficient proliferative response to FGF restimulation. A
      similar effect results following treatment with the anti-inflammatory agents
      aspirin and dexamethasone. Thus, FGF memory is mediated by proinflammatory IL1
      signaling. It may play a role in the limitation of proliferative response to
      tissue damage and prevention of wound-induced hyperplasia.

PMID- 26218438
TI  - Hispanic Parental Perceptions of Child Weight in Preschool-Aged Children: An
      Integrated Review.
AB  - BACKGROUND: Obesity continues to disproportionately affect ethnic minorities.
      Parents play an integral role in early childhood, and parental perceptions
      regarding their child's weight are key to obesity prevention. Cultural
      differences contribute to parental perceptions, and increased understandings of
      these characteristics provide a basis to address obesity in high-risk populations
      at an earlier age. The aim of this integrative review was to analyze extant
      literature to identify Hispanic parental perceptions of their preschool-aged
      child's weight status. METHODS: An integrative review of studies measuring
      Hispanic parental perception was conducted. Computerized searches were completed
      using MEDLINE, PubMed, CINHAL, Eric, and PsychINFO. Articles were included if
      they were English, included children 2-5 years of age, included a Hispanic
      population, and evaluated parental perception of their child's weight status. A
      total of 14 articles (n=8 qualitative; n=6 quantitative) met criteria and were
      included in the review. Cooper's integrative review methodology was used, and
      articles were evaluated for quality using Polit and Beck's evidence hierarchy
      leveling system. RESULTS: The results revealed six themes of Hispanic parental
      perceptions relative to their preschool-aged child's weight: parental perception
      of body weight; relationship between child weight and health; causes and
      consequences of overweight; familial roles and influences on child weight;
      prevention of overweight; and cultural influences within the United States.
      CONCLUSIONS: This review highlights the importance of developing sociocultural
      approaches to addressing childhood obesity within the Hispanic population.
      Additional research is needed to incorporate what is known about Hispanic
      parental perceptions to positively influence behavior change during early
      childhood.

PMID- 26218439
TI  - Robust algorithm to locate heart beats from multiple physiological waveforms by
      individual signal detector voting.
AB  - Alarm fatigue is a top medical device hazard in patient monitoring that could be
      reduced by merging physiological information from multiple sensors, minimizing
      the impact of a single sensor failing. We developed a heart beat detection
      algorithm that utilizes multi-modal physiological signals (e.g.
      electrocardiogram, blood pressure, stroke volume, photoplethysmogram and electro
      encephalogram) by merging the heart beats obtained from signal-specific
      detectors. We used the PhysioNet/Computing in Cardiology Challenge 2014 training
      set to develop the algorithm, and we refined it with a mix of signals from the
      multiparameter intelligent monitoring in intensive care (MIMIC II) database and
      artificially disrupted waveforms. The algorithm had an average sensitivity of
      95.67% and positive predictive value (PPV) of 92.28% when applied to the
      PhysioNet/Computing in Cardiology Challenge 2014 200 record training set. On a
      refined dataset obtained by removing 5 records with arrhythmias and inconsistent
      reference annotations we obtained an average sensitivity of 97.43% and PPV of
      94.17%. Algorithm performance was assessed with the Physionet Challenge 2014 test
      set that consisted of 200 records (each up to 10 min length) containing multiple
      physiological signals and reference annotations verified by the
      PhysioNet/Computing in Cardiology Challenge 2014 organizers. Our algorithm had a
      sensitivity of 92.74% and PPV of 87.37% computed over all annotated beats, and a
      record average sensitivity of 91.08%, PPV of 86.96% and an overall score (average
      of all 4 measures) of 89.53%. Our algorithm is an example of a data fusion
      approach that can improve patient monitoring and reduce false alarms by reducing
      the effect of individual signal failures. 

PMID- 26218440
TI  - Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor.
AB  - BACKGROUND AND PURPOSE: Cannabidiol has been reported to act as an antagonist at
      cannabinoid CB1 receptors. We hypothesized that cannabidiol would inhibit
      cannabinoid agonist activity through negative allosteric modulation of CB1
      receptors. EXPERIMENTAL APPROACH: Internalization of CB1 receptors, arrestin2
      recruitment, and PLCbeta3 and ERK1/2 phosphorylation, were quantified in HEK 293A
      cells heterologously expressing CB1 receptors and in the STHdh(Q7/Q7) cell model
      of striatal neurons endogenously expressing CB1 receptors. Cells were treated
      with 2-arachidonylglycerol or Delta(9)-tetrahydrocannabinol alone and in
      combination with different concentrations of cannabidiol. KEY RESULTS:
      Cannabidiol reduced the efficacy and potency of 2-arachidonylglycerol and
      Delta(9)-tetrahydrocannabinol on PLCbeta3- and ERK1/2-dependent signalling in
      cells heterologously (HEK 293A) or endogenously (STHdh(Q7/Q7)) expressing CB1
      receptors. By reducing arrestin2 recruitment to CB1 receptors, cannabidiol
      treatment prevented internalization of these receptors. The allosteric activity
      of cannabidiol depended upon polar residues being present at positions 98 and 107
      in the extracellular amino terminus of the CB1 receptor. CONCLUSIONS AND
      IMPLICATIONS: Cannabidiol behaved as a non-competitive negative allosteric
      modulator of CB1 receptors. Allosteric modulation, in conjunction with effects
      not mediated by CB1 receptors, may explain the in vivo effects of cannabidiol.
      Allosteric modulators of CB1 receptors have the potential to treat CNS and
      peripheral disorders while avoiding the adverse effects associated with
      orthosteric agonism or antagonism of these receptors.

PMID- 26218441
TI  - Induction of miR-132 and miR-212 Expression by Glucagon-Like Peptide 1 (GLP-1) in
      Rodent and Human Pancreatic beta-Cells.
AB  - Better understanding how glucagon-like peptide 1 (GLP-1) promotes pancreatic beta
      cell function and/or mass may uncover new treatment for type 2 diabetes. In this
      study, we investigated the potential involvement of microRNAs (miRNAs) in the
      effect of GLP-1 on glucose-stimulated insulin secretion. miRNA levels in INS-1
      cells and isolated rodent and human islets treated with GLP-1 in vitro and in
      vivo (with osmotic pumps) were measured by real-time quantitative PCR. The role
      of miRNAs on insulin secretion was studied by transfecting INS-1 cells with
      either precursors or antisense inhibitors of miRNAs. Among the 250 miRNAs
      surveyed, miR-132 and miR-212 were significantly up-regulated by GLP-1 by greater
      than 2-fold in INS-1 832/3 cells, which were subsequently reproduced in freshly
      isolated rat, mouse, and human islets, as well as the islets from GLP-1 infusion
      in vivo in mice. The inductions of miR-132 and miR-212 by GLP-1 were correlated
      with cAMP production and were blocked by the protein kinase A inhibitor H-89 but
      not affected by the exchange protein activated by cAMP activator 8-pCPT-2'-O-Me
      cAMP-AM. GLP-1 failed to increase miR-132 or miR-212 expression levels in the
      832/13 line of INS-1 cells, which lacks robust cAMP and insulin responses to GLP
      1 treatment. Overexpression of miR-132 or miR-212 significantly enhanced glucose
      stimulated insulin secretion in both 832/3 and 832/13 cells, and restored insulin
      responses to GLP-1 in INS-1 832/13 cells. GLP-1 increases the expression of
      miRNAs 132 and 212 via a cAMP/protein kinase A-dependent pathway in pancreatic
      beta-cells. Overexpression of miR-132 or miR-212 enhances glucose and GLP-1
      stimulated insulin secretion. 

PMID- 26218443
TI  - Asymmetry of Cerebral Hemodynamic Response to Incremental Cycling Exercise.
AB  - PURPOSE: Exercise is known to result in hemodynamic changes in the bilateral
      prefrontal cortex. The aim of this study was to investigate hemodynamic changes
      in right and left hemispheres of the prefrontal cortex (PFC) during incremental
      cycling exercise. METHODS: After 10 min rest, 9 participants (mean age 26.6 +/-
      2.5 y, mass 77.5 +/- 9.7 kg, stature 1.79 +/- 0.9 m) cycled at 100-150 W for 4
      min. Thereafter, resistance was increased by 25 W every 4 min until exhaustion
      (EXH). Respiratory exchange and concentrations of oxy- ([HbO2]), deoxy- ([(HHb]),
      and total hemoglobin ([Hb(tot)]) in the PFC were continuously measured. Data were
      averaged for 60 s at rest and preceding ventilatory threshold 1 (VT1), VT2, and
      volitional EXH and after 5 min recovery. Subjective ratings of affect were
      measured at VT1, VT2, VT1 minus 25 W (VT1-25W), and VT2 plus 25 W (VT2+25W).
      RESULTS: There were no between-hemispheres differences in [HbO2] or [Hb(tot)] at
      rest, VT1, or recovery or in [HHb] at any point. Right-hemisphere [HbO2] and
      [Hb(tot)] were significantly greater than left at VT2 (P = .01 and P = .02) and
      EXH (P = .03 and P = .02). Affect was significantly greater at VT1-25W vs VT2 and
      VT2+25W and at VT1 and VT2 vs VT2+25W (P < .01-.03). CONCLUSIONS: To the authors'
      knowledge, this is the first study to describe an exercise-state-dependent change
      in PFC asymmetry during incremental exercise. The asymmetry detected coincided
      with a decrease in affect scores in agreement with the PFC-asymmetry hypothesis.

PMID- 26218442
TI  - Cross Talk Between GH-Regulated Transcription Factors HNF6 and CUX2 in Adult
      Mouse Liver.
AB  - Hepatocyte-enriched nuclear factor (HNF)6 and CUX2 are GH and STAT5-regulated
      homeobox transcription factors. CUX2 shows female-specific expression and
      contributes to liver sex differences by repressing many male-biased genes and
      inducing many female-biased genes, whereas HNF6 is expressed at similar levels in
      male and female liver. In cell-based transfection studies, CUX2 inhibited HNF6
      transcriptional regulation of the sex-specific gene promoters CYP2C11 and
      CYP2C12, blocking HNF6 repression of CYP2C11 and HNF6 activation of CYP2C12.
      These inhibitory actions of CUX2 can be explained by competition for HNF6 DNA
      binding, as demonstrated by in vitro EMSA analysis and validated in vivo by
      global analysis of the HNF6 cistrome. Approximately 40 000 HNF6-binding sites
      were identified in mouse liver chromatin, including several thousand sites
      showing significant sex differences in HNF6 binding. These sex-biased HNF6
      binding sites showed strong enrichment for correspondingly sex-biased DNase
      hypersensitive sites and for proximity to genes showing local sex-biased
      chromatin marks and a corresponding sex-biased expression. Further, approximately
      90% of the genome-wide binding sites for CUX2 were also bound by HNF6. These
      HNF6/CUX2 common binding sites were enriched for genomic regions more accessible
      in male than in female mouse liver chromatin and showed strongest enrichment for
      male-biased genes, suggesting CUX2 displacement of HNF6 as a mechanism to explain
      the observed CUX2 repression of male-biased genes in female liver. HNF6 binding
      was sex independent at a majority of its binding sites, and HNF6 peaks were
      frequently associated with cobinding by multiple other liver transcription
      factors, consistent with HNF6 playing a global regulatory role in both male and
      female liver. 

PMID- 26218444
TI  - Dementia incidence declined in African-Americans but not in Yoruba.
AB  - INTRODUCTION: To compare dementia incidence of African-American and Yoruba
      cohorts aged >=70 years enrolled in 1992 and 2001. METHODS: African-Americans
      residing in Indianapolis and Yoruba in Ibadan, Nigeria without dementia were
      enrolled in 1992 and 2001 and evaluated every 2-3 years until 2009. The cohorts
      consist of 1440 African-Americans, 1774 Yoruba in 1992 and 1835 African-Americans
      and 1895 Yoruba in the 2001 cohorts aged >=70 years. RESULTS: In African
      Americans, dementia and Alzheimer's disease (AD) incidence rates were
      significantly lower in 2001 than 1992 for all age groups except the oldest group.
      The overall standardized annual dementia incidence rates were 3.6% (95%
      confidence interval [CI], 3.2%-4.1%) in the 1992 cohort and 1.4% (95% CI, 1.2%
      1.7%) in the 2001 cohort. There was no significant difference in dementia or AD
      incidence between the Yoruba cohorts. DISCUSSION: Future research is needed to
      explore the reasons for the differential changes in incidence rates in these two
      populations.

PMID- 26218447
TI  - Population pharmacokinetics of edoxaban in patients with symptomatic deep-vein
      thrombosis and/or pulmonary embolism--the Hokusai-VTE phase 3 study.
AB  - AIMS: This study characterized the population pharmacokinetics of edoxaban in
      patients with symptomatic deep-vein thrombosis and/or pulmonary embolism in the
      Hokusai-VTE phase 3 study. The impact of the protocol-specified 50% dose
      reductions applied to patients with body weight <= 60 kg, creatinine clearance
      (CL(cr)) of 30 to 50 ml min(-1) or concomitant P-glycoprotein inhibitor on
      edoxaban exposure was assessed using simulations. METHODS: The sparse data from
      Hokusai-VTE, 9531 concentrations collected from 3707 patients, were pooled with
      data from 13 phase 1 studies. In the analysis, the covariate relationships used
      for dose reductions were estimated and differences between healthy subjects and
      patients as well as additional covariate effects of age, race and gender were
      explored based on statistical and clinical significance. RESULTS: A linear two
      compartment model with first order absorption preceded by a lag time best
      described the data. Allometrically scaled body weight was included on disposition
      parameters. Apparent clearance was parameterized as non-renal and renal. The
      latter increased non-linearly with increasing CL(cr). Compared with healthy
      volunteers, inter-compartmental clearance and the CL(cr) covariate effect were
      different in patients (+64.6% and +274%). Asian patients had a 22.6% increased
      apparent central volume of distribution. The effect of co-administration of P
      glycoprotein inhibitors seen in phase 1 could not be confirmed in the phase 3
      data. Model-based simulations revealed lower exposure in dose-reduced compared
      with non-dose-reduced patients. CONCLUSIONS: The adopted dose-reduction strategy
      resulted in reduced exposure compared with non-dose-reduced, thereby
      overcompensating for covariate effects. The clinical impact of these differences
      on safety and efficacy remains to be evaluated.

PMID- 26218448
TI  - Optimization of simultaneous removal of Cr (VI) and phenol by a native bacterial
      consortium: its use for bioaugmentation of co-polluted effluents.
AB  - AIMS: This study was designed to isolate, identify and characterize micro
      organisms or mixed cultures capable of simultaneously removing Cr (VI) and phenol
      in the surrounding area of a tannery localized in Elena, Cordoba, Argentina. In
      addition, nutritional and physical factors were optimized in order to improve the
      removal efficiency in a real effluent. METHODS AND RESULTS: The consortium SFC
      500-1, composed of two bacterial strains belonging to Acinetobacter and Bacillus
      genus, was isolated from the heavily polluted wastewater discharge channel of a
      local tannery. SFC 500-1 was able to remove phenol at environmentally relevant
      concentrations (1000 mg l(-1) ) and reduce Cr (VI) to Cr (III), which was
      immobilized in the bacterial biomass. The consortium simultaneously removed these
      contaminants under a wide range of physicochemical conditions and different
      growth media, even in a tannery effluent. CONCLUSION: The ability of SFC 500-1 to
      simultaneously reduce Cr (VI) and degrade phenol in different synthetic growth
      media and even in the effluent from which it was isolated with high efficiency
      makes this consortium a potential candidate for the biotreatment of effluents.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This finding is important, taking into
      account that industrial effluents present complex mixtures of toxic substances as
      well as native flora which often affect the bioremediation process. Considering
      the ecological advantages of using native bacteria for bioremediation, as well as
      the high efficiency of the consortium SFC 500-1 to simultaneously remove Cr (VI)
      and phenol, this could be a suitable biological system to improve the
      biotreatment of polluted effluents through a bioaugmentation strategy.

PMID- 26218449
TI  - Radiation dosimetry estimates of (18)F-alfatide II based on whole-body PET
      imaging of mice.
AB  - We estimated the dosimetry of (18)F-alfatide II with the method established by
      MIRD based on biodistribution data of mice. Six mice (three females and three
      males) were scanned for 160min on an Inveon MicroPET/CT scanner after injection
      of (18)F-alfatide II via tail vein. Eight source organs were delineated on the CT
      images and their residence times calculated. The data was then converted to human
      using scaling factors based on organ and body weight. The absorbed doses for
      human and the resulting effective dose were computed by OLINDA 1.1 software. The
      highest absorbed doses was observed in urinary bladder wall (male 0.102mGy/MBq,
      female 0.147mGy/MBq); and the lowest one was detected in brain (male
      0.0030mGy/MBq, female 0.0036). The total effective doses were 0.0127mSv/MBq for
      male and 0.0166 mSv/MBq for female, respectively. A 370-MBq injection of (18)F
      alfatide II led to an estimated effective dose of 4.70mSv for male and 6.14mSv
      for female. The potential radiation burden associated with (18)F-alfatide II/PET
      imaging therefore is comparable to other PET examinations. 

PMID- 26218450
TI  - Chlorine signal attenuation in concrete.
AB  - The intensity of prompt gamma-ray was measured at various depths from chlorine
      contaminated silica fume (SF) concrete slab concrete specimens using portable
      neutron generator-based prompt gamma-ray setup. The intensity of 6.11MeV chloride
      gamma-rays was measured from the chloride contaminated slab at distance of 15.25,
      20.25, 25.25, 30.25 and 35.25cm from neutron target in a SF cement concrete slab
      specimens. Due to attenuation of thermal neutron flux and emitted gamma-ray
      intensity in SF cement concrete at various depths, the measured intensity of
      chlorine gamma-rays decreases non-linearly with increasing depth in concrete. A
      good agreement was noted between the experimental results and the results of
      Monte Carlo simulation. This study has provided useful experimental data for
      evaluating the chloride contamination in the SF concrete utilizing gamma-ray
      attenuation method. 

PMID- 26218451
TI  - Finite and infinite system gamma ray buildup factor calculations with detailed
      physics.
AB  - Examination of physical interactions of photons in materials is a significant
      subject for buildup factor studies. In most of the buildup calculations, by
      default, coherent (Rayleigh) scattering is ignored and the Compton scattering is
      modeled by free-electron Klein-Nishina formula with "simple physics" treatment.
      In this work, photon buildup factors are calculated for many different cases
      including "detailed physics" by taking into account coherent and bound-electron
      Compton scatterings with the Monte Carlo code, MCNP5, and the results are
      compared with the literature values. They are computed for point isotropic photon
      sources up to depths of 20 mean free paths and at the three photon energies most
      widely used (0.06, 0.6 and 6MeV). Calculations are made for both finite and
      infinite homogeneous ordinary water media. It is concluded that Coherent
      scattering is very dominant at low energies and for deep penetrations and assumed
      physical approximation (simple/detailed, finite/infinite) is the critical point
      for determining shielding material dimensions. After all, it can be stated that
      all parametric assumptions should be clearly given and indicated in the
      tabulation of photon buildup factors. 

PMID- 26218452
TI  - A Case of Subcutaneous Granuloma Annulare (SGA) in the Scalp of a Child:
      Histological Findings.
AB  - Subcutaneous granuloma annulare is type of granuloma annulare which usually
      occurs in children. Scalp involvement is rare. The authors report a 3-year-old
      girl with subcutaneous granuloma annulare confirmed by imaging and histologic
      findings. No treatment was provided. The patient was followed for 6 months with
      no considerable complications. 

PMID- 26218453
TI  - Synergistic Effect between Metal-Nitrogen-Carbon Sheets and NiO Nanoparticles for
      Enhanced Electrochemical Water-Oxidation Performance.
AB  - Identifying effective means to improve the electrochemical performance of oxygen
      evolution catalysts represents a significant challenge in several emerging
      renewable energy technologies. Herein, we consider metal-nitrogen-carbon sheets
      which are commonly used for catalyzing the oxygen-reduction reaction (ORR), as
      the support to load NiO nanoparticles for the oxygen-evolution reaction (OER).
      FeNC sheets, as the advanced supports, synergistically promote the NiO
      nanocatalysts to exhibit superior performance in alkaline media, which is
      confirmed by experimental observations and density functional theory (DFT)
      calculations. Our findings show the advantages in considering the support effect
      for designing highly active, durable, and cost-effective OER electrocatalysts. 

PMID- 26218454
TI  - Chemoselective Carbene insertion into the N-H Bond over O-H Bond Using a Well
      Defined Single Site (P-P)Cu(I) Catalyst.
AB  - Phosphine-coordinated air-stable Cu(I) catalyst (1) has been synthesized and
      characterized. Catalyst 1 is found to be active toward highly chemoselective
      carbene insertion into the N-H bond over the O-H bond and also over the formation
      of olefins when numerous aminophenols were treated with a variety of alpha-aryl
      diazoesters under normal experimental conditions. 

PMID- 26218455
TI  - Comparison of Social Trust's effect on suicide ideation between urban and non
      urban areas: The Case of Japanese Adults in 2006.
AB  - An increasing number of studies have addressed the determinants of suicide.
      Social capital is a key factor in preventing suicide. However, little is known
      about the experience of suicide ideation using subjective values. From the
      viewpoint of suicide prevention, it is worth examining how people think of
      suicide. This paper attempts to examine the effect of social capital on suicide
      ideation. Furthermore, the paper compares the effect of social capital between
      urban and non-urban areas. In this paper, urban areas are equivalent to mega
      cities with populations over one million. Non-urban areas are cities with
      populations of less than one million, towns and villages. Individual-level data
      from the Japanese General Social Surveys (JGSSs) are used. The survey, which was
      conducted in 2006, provides information about the subjective value of suicide
      ideation. The survey was answered by 1413 subjects with a mean age of 54.5. Of
      the subjects, 49% were male. Social trust is used to measure the degree of social
      capital, and the outcome of interest is suicide ideation within the past 5 years.
      After controlling for various factors, the major findings are that both
      individual-level social trust and social trust accumulated in one's residential
      administrative district reduce the probability that one will consider suicide.
      After dividing the sample into urban and non-urban residents, particularized
      trust plays a role in deterring suicide ideation in urban areas, while
      generalized trust plays a role in deterring suicide ideation in non-urban areas.
      The effect of each type of trust depends on its scarcity in residential areas. 

PMID- 26218456
TI  - Point mutations in Escherichia coli DNA pol V that confer resistance to non
      cognate DNA damage also alter protein-protein interactions.
AB  - Y-family DNA polymerases are important for conferring cellular resistance to DNA
      damaging agents in part due to their specialized ability to copy damaged DNA. The
      Escherichia coli Y-family DNA polymerases are encoded by the umuDC and dinB
      genes. UmuC and the cleaved form of UmuD, UmuD', form UmuD'2C (pol V), which is
      able to bypass UV photoproducts such as cyclobutane pyrimidine dimers and 6-4
      thymine-thymine dimers, whereas DinB is specialized to copy N(2)-dG adducts, such
      as N(2)-furfuryl-dG. To better understand this inherent specificity, we used
      hydroxylamine to generate a random library of UmuC variants from which we then
      selected those with the ability to confer survival to nitrofurazone (NFZ), which
      is believed to cause N(2)-furfuryl-dG lesions. We tested the ability of three of
      the selected UmuC variants, A9V, H282P, and T412I, to bypass N(2)-furfuryl-dG in
      vitro, and discovered that pol V containing UmuC A9V has overall modestly better
      primer extension activity than WT pol V, whereas the UmuC T412I and UmuC H282P
      mutations result in much lower primer extension efficiency. Upon further
      characterization, we found that the ability of the UmuC variant A9V to render
      cells UV-mutable is dependent on the proper length of the arm of UmuD'. Cells
      harboring UmuC variants T412I and H282P show enhanced cleavage of UmuD to form
      UmuD', which, together with our other observations, suggests that this may be due
      to a disruption of a direct interaction between UmuC and UmuD. Thus, we find that
      protein interactions as well as protein conformation appear to be crucial for
      resistance to specific types of DNA damage. 

PMID- 26218458
TI  - How Does the Local Electrostatic Field Influence Emitted Wavelengths and
      Bioluminescent Intensities of Modified Heteroaromatic Luciferins?
AB  - The firefly chromophore, oxyluciferin, is in the pocket of the firefly luciferase
      and is surrounded by the side-chains of some amino acid residues. The charged
      residues produce the local electrostatic field (LEF) around the oxyluciferin. The
      emitted wavelengths and intensities of the oxyluciferin and its heterocyclic
      analogs under the LEF are examined. The common overlapping volumes of the HOMO
      and LUMO explain why the oscillator strengths vary under the LEF. Three average
      Ex change rates of the first excited energy are introduced to measure what
      luciferins are more sensitive to the LEF. The first excited energies and
      intensities in two enzymatic-like microenvironments are simulated via the LEF.
      The oscillator strengths and the net electric charges of the O6' and the O4 are
      applied to explain the experimental bioluminescent intensities. 

PMID- 26218457
TI  - Effect of overuse-induced tendinopathy on tendon healing in a rat supraspinatus
      repair model.
AB  - Supraspinatus tears often result in the setting of chronic tendinopathy. However,
      the typical repair model utilizes an acute injury. In recognition of that
      distinction, our laboratory developed an overuse animal model; however it is
      unclear whether induced overuse is necessary in the repair model. We studied the
      repair properties of overuse-induced tendons compared to normal tendons. We
      hypothesized that histological and mechanical properties would not be altered
      between the overuse-induced and normal tendons 1 and 4 weeks after repair. Thirty
      one adult male Sprague-Dawley rats were subjected to either overuse or cage
      activity for 4 weeks prior to bilateral supraspinatus tendon repair surgery. Rats
      were sacrificed at 1 and 4 weeks post-surgery and evaluated for histology and
      mechanics. Results at 1 week showed no clear histologic changes, but increased
      inflammatory protein expression in overuse tendons. At 4 weeks, percent
      relaxation was slightly increased in the overuse group. No other alterations in
      mechanics or histology were observed. Our results suggest that the effects of the
      surgical injury overshadow the changes evoked by overuse. Because clinically
      relevant mechanical parameters were not altered in the overuse group, we conclude
      that when examining tendons 4 weeks after repair in the classic rat supraspinatus
      model, inducing overuse prior to surgery is likely to be unnecessary.

PMID- 26218459
TI  - Optimal dissection for transanal total mesorectal excision using modified CO2
      insufflation and smoke extraction.
AB  - AIM: The new approach of transanal total mesorectal excision is technically
      challenging and demands a stable field of dissection with optimal view of
      anatomical landmarks. We aimed to describe and demonstrate a modification of both
      the insufflation of carbon dioxide and smoke evacuation, in order to optimize
      dissection. METHOD: The comparison of standard insufflation to an AirSeal
      platform demonstrates a clear difference. This is shown in the accompanying video
      recordings. RESULTS: A more stable pneumorectum and better smoke evacuation as
      well as more convenient and precise dissection were achieved with the AirSeal
      platform. CONCLUSION: Using the technique outlined, the operating surgeon is able
      to perform the surgical dissection in a stable operating environment with
      increased visibility compared to the standard approach.

PMID- 26218462
TI  - Reply to low expression of chloride channel accessory 1 predicts a poor prognosis
      in colorectal cancer: The question is still open.

PMID- 26218460
TI  - Systematic Backbone Conformational Constraints on a Cyclic Melanotropin Ligand
      Leads to Highly Selective Ligands for Multiple Melanocortin Receptors.
AB  - Human melanocortin receptors (hMCRs) have been challenging targets to develop
      ligands that are explicitly selective for each of their subtypes. To modulate the
      conformational preferences of the melanocortin ligands and improve the
      biofunctional agonist/antagonist activities and selectivities, we have applied a
      backbone N-methylation approach on Ac-Nle-c[Asp-His-D-Nal(2')-Arg-Trp-Lys]-NH2
      (Ac-Nle(4)-c[Asp(5),D-Nal(2')(7),Lys(10)]-NH2), a nonselective cyclic peptide
      antagonist at hMC3R and hMC4R and an agonist at hMC1R and hMC5R. Systematic N
      methylated derivatives of Ac-Nle(4)-c[Asp(5),D-Nal(2')(7),Lys(10)]-NH2, with all
      possible backbone N-methylation combinations, have been synthesized and examined
      for their binding and functional activities toward melanocortin receptor subtypes
      1, 3, 4, and 5 (hMCRs). Several N-methylated analogues are selective and potent
      agonists or antagonists for hMC1R or hMC5R or have selective antagonist activity
      for hMC3R. The selective hMC1R ligands show strong binding for human melanoma
      cells. We have also discovered the first universal antagonist (compound 19) for
      all subtypes of hMCRs.

PMID- 26218463
TI  - Evaluation of new alternatives in wastewater treatment plants based on dynamic
      modelling and life cycle assessment (DM-LCA).
AB  - With a view to quantifying the energy and environmental advantages of Urine
      Source-Separation (USS) combined with different treatment processes, five
      wastewater treatment plant (WWTP) scenarios were compared to a reference scenario
      using Dynamic Modelling (DM) and Life Cycle Assessment (LCA), and an integrated
      DM-LCA framework was thus developed. Dynamic simulations were carried out in
      BioWin((r)) in order to obtain a realistic evaluation of the dynamic behaviour
      and performance of plants under perturbation. LCA calculations were performed
      within Umberto((r)) using the Ecoinvent database. A PythonTM interface was used
      to integrate and convert simulation data and to introduce them into Umberto((r))
      to achieve a complete LCA evaluation comprising foreground and background
      processes. Comparisons between steady-state and dynamic simulations revealed the
      importance of considering dynamic aspects such as nutrient and flow peaks. The
      results of the evaluation highlighted the potential of the USS scenario for
      nutrient recovery whereas the Enhanced Primary Clarification (EPC) scenario gave
      increased biogas production and also notably decreased aeration consumption,
      leading to a positive energy balance. Both USS and EPC scenarios also showed
      increased stability of plant operation, with smaller daily averages of total
      nitrogen and phosphorus. In this context, USS and EPC results demonstrated that
      the coupled USS + EPC scenario and its combinations with agricultural spreading
      of N-rich effluent and nitritation/anaerobic deammonification could present an
      energy-positive balance with respectively 27% and 33% lower energy requirements
      and an increase in biogas production of 23%, compared to the reference scenario.
      The coupled scenarios also presented lesser environmental impacts (reduction of
      31% and 39% in total endpoint impacts) along with effluent quality well within
      the specified limits. The marked environmental performance (reduction of global
      warming) when nitrogen is used in agriculture shows the importance of future
      research on sustainable solutions for nitrogen recovery. The contribution
      analysis of midpoint impacts also showed hotspots that it will be important to
      optimize further, such as plant infrastructure and direct N2O emissions. 

PMID- 26218464
TI  - Characterization of microflora and transformation of organic matters in urban
      sewer system.
AB  - A study was conducted using a pilot sewer system consisting of 35 sequential
      sections, totalling 1200 m of gravity pipe. Urban sewage flowed into the sewer
      system at a constant flow rate until it reached physical and microbiological
      steady states. Microflora in the biofilm that attached to the inner surface along
      the pipe length were analysed. The organic compositions in both the liquid and
      gaseous phases of the sewer system were monitored. The results showed that
      typical fermentation bacteria, such as bacteroidetes and bacillus, were abundant
      in the system, indicating that the anoxic environment (DO = 0.3 mg/L) was
      suitable for fermentative bacterial growth. This resulted in a substantial
      reduction of the chemical oxygen demand (COD) along the pipe length and an
      increase of the biodegradable oxygen demand/chemical oxygen demand (BOD/COD)
      ratio from 0.68 at the beginning of the sewer system to 0.84 at the end of the
      sewer system; this was an indication of a transformation of organic matters from
      less-biodegradable to more-biodegradable products. Via molecular weight (MW)
      analysis, it was further identified that the larger organic molecules (MW >
      10,000 Da) were transformed into products with smaller molecular weights.
      Regarding the fermentation products, the concentrations of the volatile fatty
      acids (VFAs) increased dramatically in the initial 600-m sections and then
      remained constant for the later sections except for the end section of the sewer;
      acetic acid was found to be the primary product of the VFAs. Gaseous carbon
      dioxide (CO2) and methane (CH4) were found to increase along the length of the
      sewer system, whereas the concentrations of ethanol, lactic acid, and hydrogen
      (H2) were high at the beginning of the sewer and then decreased in the rear
      sections of the sewer system. It could thus be concluded that in an urban
      wastewater sewer system, fermentative microflora could perform important roles in
      contributing to organic matter removal and/or improving the biodegradability of
      organic matter. 

PMID- 26218465
TI  - Removal of organic pollutants from oak leachate in pilot scale wetland systems:
      How efficient are aeration and vegetation treatments?
AB  - This study investigated the effects of aeration and/or vegetation in experimental
      constructed wetlands (CWs) as mesocosms on the removal of pollutants in oak wood
      leachate. Twelve outdoor wetland mesocosms, with randomized replicated treatment
      combinations of vegetation (Phragmites australis) and aeration was monitored
      during the second and third year after construction. The investigation included
      control tanks with no aeration and no vegetation. The parameters monitored were
      polyphenols (PPs), chemical oxygen demand (COD) and water colour. The reduction
      of COD after 28 days was approx. 50% and more than 50% of PPs, whereas only 40%
      of the water colour was removed. Aeration increased the effect of both COD and PP
      removal. The vegetation treatment had a small but significant effect on removal
      of COD. The vegetation + aeration treatment, as well as aeration alone, increased
      the removal efficiency of COD from 9.5 g m(-3) d(-1) in the control to 11 g m(-3)
      d(-1). The results suggest that CWs can be used to treat stormwater contaminated
      by oak wood leachate. Further, it is suggested that the main processes for
      removal of pollutants in the leachate occur in the open-water habitat and that
      the hydraulic retention time is more important for removal than aeration and
      vegetation related processes. 

PMID- 26218466
TI  - Potential of pulsed corona discharges generated in water for the degradation of
      persistent pharmaceutical residues.
AB  - Anthropogenic pollutants and in particular pharmaceutical residues are a
      potential risk for potable water where they are found in increasing
      concentrations. Different environmental effects could already be linked to the
      presence of pharmaceuticals in surface waters even for low concentrations. Many
      pharmaceuticals withstand conventional water treatment technologies.
      Consequently, there is a need for new water purification techniques. Advanced
      oxidation processes (AOP), and especially plasmas with their ability to create
      reactive species directly in water, may offer a promising solution. We developed
      a plasma reactor with a coaxial geometry to generate large volume corona
      discharges directly in water and investigated the degradation of seven
      recalcitrant pharmaceuticals (carbamazepine, diatrizoate, diazepam, diclofenac,
      ibuprofen, 17alpha-ethinylestradiol, trimethoprim). For most substances we
      observed decomposition rates from 45% to 99% for treatment times of 15-66 min.
      Especially ethinylestradiol and diclofenac were readily decomposed. As an
      inherent advantage of the method, we found no acidification and only an
      insignificant increase in nitrate/nitrite concentrations below legal limits for
      the treatment. Studies on the basic plasma chemical processes for the model
      system of phenol showed that the degradation is primarily caused by hydroxyl
      radicals. 

PMID- 26218467
TI  - Zinc controls RyR2 activity during excitation-contraction coupling.

PMID- 26218468
TI  - Torsional Detwinning Domino in Nanotwinned One-Dimensional Nanostructures.
AB  - How to maintain sustained deformation in one-dimensional nanostructures without
      localized failure is an important question for many applications of
      nanotechnology. Here we report a phenomenon of torsional detwinning domino that
      leads to giant rotational deformation without localized failure in nanotwinned
      one-dimensional metallic nanostructures. This mechanism is demonstrated in
      nanotwinned Cu nanorods via molecular dynamics simulations, where coherent twin
      boundaries are transformed into twist boundaries and then dissolved one by one,
      resulting in practically unlimited rotational deformation. This finding
      represents a fundamental advance in our understanding of deformation mechanisms
      in one-dimensional metallic nanostructures. 

PMID- 26218469
TI  - Computer Tablet Distraction in Children Receiving an Injection.
AB  - OBJECTIVE: To evaluate the effectiveness of a computer tablet as a distraction
      tool for minimizing pain and distress in children undergoing an injection.
      DESIGN: Using an experimental design, the subjects were randomly assigned to
      either participate in tablet distraction or receive no distraction during an
      injection. SETTING: A pediatric clinic in a small city in the Southeast region of
      the United States. SUBJECTS: Forty-one children, ages 4-11 years, who were
      receiving an immunization and their parents. METHODS: During an injection,
      children either participated in distraction using a computer tablet or did not
      receive distraction according to their group assignment. Children's emotional
      response was assessed using a behavioral observation to examine distress. Pain
      was also measured using a behavior observation scale. After the injection,
      children reported the level of pain they felt during the injection. RESULTS: A
      significant difference was found for pain, both self-reported and observed, and
      observed emotions. Children receiving distraction using a tablet displayed
      significantly higher amounts of pain and negative emotions. Gender differences in
      pain and emotions were found with females having a significantly higher amount of
      pain and negative emotions. CONCLUSIONS: The use of a tablet as a distraction was
      not effective in decreasing pain and distress in children receiving an injection.

PMID- 26218470
TI  - Effect of proton-conduction in electrolyte on electric efficiency of multi-stage
      solid oxide fuel cells.
AB  - Solid oxide fuel cells (SOFCs) are promising electrochemical devices that enable
      the highest fuel-to-electricity conversion efficiencies under high operating
      temperatures. The concept of multi-stage electrochemical oxidation using SOFCs
      has been proposed and studied over the past several decades for further improving
      the electrical efficiency. However, the improvement is limited by fuel dilution
      downstream of the fuel flow. Therefore, evolved technologies are required to
      achieve considerably higher electrical efficiencies. Here we present an
      innovative concept for a critically-high fuel-to-electricity conversion
      efficiency of up to 85% based on the lower heating value (LHV), in which a high
      temperature multi-stage electrochemical oxidation is combined with a proton
      conducting solid electrolyte. Switching a solid electrolyte material from a
      conventional oxide-ion conducting material to a proton-conducting material under
      the high-temperature multi-stage electrochemical oxidation mechanism has proven
      to be highly advantageous for the electrical efficiency. The DC efficiency of 85%
      (LHV) corresponds to a net AC efficiency of approximately 76% (LHV), where the
      net AC efficiency refers to the transmission-end AC efficiency. This evolved
      concept will yield a considerably higher efficiency with a much smaller
      generation capacity than the state-of-the-art several tens-of-MW-class most
      advanced combined cycle (MACC). 

PMID- 26218471
TI  - [Imaging findings in BCGitis--Bacillus-Calmette-Guerin-Infektion (BCGitis) after
      intravesical BCG instillation therapy in urothelial carcinoma of the urinary
      bladder].

PMID- 26218472
TI  - [German Glossary for Structured Reporting in Chest Radiology].

PMID- 26218473
TI  - [Glossary of Terms for Thoracic Imaging--German Version of the Fleischner Society
      Recommendations].
AB  - The Fleischner Society has published several recommendations for terms for
      thoracic imaging. The most recent glossary was released in 2008. One glossary in
      German language was published in 1996. This review provides an updated German
      glossary of terms for thoracic imaging. It closely adheres to the Fleischner
      Society terminology. In some instances adaptions to the usage of German language
      were necessary, as well as some additions of terms which were later defined or
      redefined. These deviations are summarized in a revision report. KEY POINTS: The
      Fleischner Society has published a revised version of her glossary of terms for
      thoracic imaging in 2008. This paper presents a German adaption of this glossary.
      Some terms not contained in the original version have been added. The general use
      of the presented terminology in radiological reports is recommended.

PMID- 26218477
TI  - The homopentameric chlorite dismutase from Magnetospirillum sp.
AB  - Chlorite dismutase (Cld) is a b-type heme containing enzyme that catalyzes the
      reduction of chlorite into chloride plus dioxygen. This enzyme has gained
      attention because it can be used in the development of bioremediation processes,
      biosensors, and controlled dioxygen production. In the present work, Cld was
      purified from Magnetospirillum sp. cells cultured anaerobically with
      acetate/perchlorate until stationary phase. Biochemical, spectroscopic and X-ray
      crystallography methods showed that Cld from Magnetospirillum sp. is a ~140 kDa
      homopentamer comprising ~27.8 kDa monomers. Preliminary X-ray crystallography
      studies confirmed the quaternary structure and the presence of one b-type heme
      per monomer. The EPR spectroscopic signature of the as-purified Cld samples is
      affected by the buffer composition used during the purification. Potassium
      phosphate buffer is the only buffer that affected neither the spectral nor the
      kinetic properties of Cld. Kinetic studies in solution revealed that Cld from
      Magnetospirillum sp. decomposes chlorite at high turnover rates with optimal
      pH6.0. A temperature below 10  degrees C is required to avoid enzyme inactivation
      due to cofactor bleaching during turnover, and to achieve full substrate
      consumption. Cld kinetic parameters were not affected when kinetic assays were
      performed in the presence of air or under argon atmosphere, but chloride is a
      weak mixed inhibitor that modifies the EPR signal of as-prepared samples.

PMID- 26218478
TI  - Characterization of morphological trunk changes in camptocormia patients.

PMID- 26218480
TI  - Keeping It Real: Advocating for Patients and Nurses.

PMID- 26218479
TI  - Structure and Mechanism of the Influenza A M218-60 Dimer of Dimers.
AB  - We report a magic angle spinning (MAS) NMR structure of the drug-resistant S31N
      mutation of M218-60 from Influenza A. The protein was dispersed in diphytanoyl-sn
      glycero-3-phosphocholine lipid bilayers, and the spectra and an extensive set of
      constraints indicate that M218-60 consists of a dimer of dimers. In particular,
      ~280 structural constraints were obtained using dipole recoupling experiments
      that yielded well-resolved (13)C-(15)N, (13)C-(13)C, and (1)H-(15)N 2D, 3D, and
      4D MAS spectra, all of which show cross-peak doubling. Interhelical distances
      were measured using mixed (15)N/(13)C labeling and with deuterated protein, MAS
      at omegar/2pi = 60 kHz, omega0H/2pi = 1000 MHz, and (1)H detection of methyl
      methyl contacts. The experiments reveal a compact structure consisting of a
      tetramer composed of four transmembrane helices, in which two opposing helices
      are displaced and rotated in the direction of the membrane normal relative to a
      four-fold symmetric arrangement, yielding a two-fold symmetric structure. Side
      chain conformations of the important gating and pH-sensing residues W41 and H37
      are found to differ markedly from four-fold symmetry. The rmsd of the structure
      is 0.7 A for backbone heavy atoms and 1.1 A for all heavy atoms. This two-fold
      symmetric structure is different from all of the previous structures of M2, many
      of which were determined in detergent and/or with shorter constructs that are not
      fully active. The structure has implications for the mechanism of H(+) transport
      since the distance between His and Trp residues on different helices is found to
      be short. The structure also exhibits two-fold symmetry in the vicinity of the
      binding site of adamantyl inhibitors, and steric constraints may explain the
      mechanism of the drug-resistant S31N mutation. 

PMID- 26218481
TI  - Heat Illnesses in the Emergency Department: A Hot Topic.
AB  - The RESEARCH TO PRACTICE column is intended to improve the research critique
      skills of the advanced practice registered nurse (APRN) and to assist with the
      translation of research into practice. For each column, a topic and a particular
      research study are selected. The stage is set with a case presentation. The
      research article is then reviewed and critiqued, and the findings are discussed
      in relation to the case presented. Our current column discusses factors
      associated with heat-related hospitalizations and deaths with implications for
      APRN practice and public health prevention strategies using the following study:
      . Summertime acute heat illness in U.S. emergency departments from 2006 through
      2010: Analysis of a nationally representative sample. Environmental Health
      Perspectives, 122(11), 1209-1215. Our case involves an adolescent athlete with
      sickle cell trait participating in athletic practice during the summer. 

PMID- 26218482
TI  - Fractures of the Scapula.
AB  - Scapular fractures require a significant amount of force to occur. These
      fractures are usually associated with major concomitant injuries and sometimes
      death. One should have a high index of suspicion in any patient who sustains a
      high-energy mechanism of injury involving the upper posterior chest. Scapular
      fractures are one of the most difficult fractures to diagnose on radiographs.
      Three-dimensional computed tomographic scans are considered the gold standard for
      scapular diagnoses. Treatment strategies vary for fractures of the scapula, but
      the site and degree of displacement will determine whether surgical intervention
      should be considered. Complications can occur in fractures that are undiagnosed
      or improperly evaluated. 

PMID- 26218483
TI  - That's a Phat Antidote: Intravenous Fat Emulsions and Toxicological Emergencies.
AB  - Health care providers in the emergency department (ED) frequently find themselves
      caring for patients who may have overdosed on a medication(s) or other toxic
      substance. These patients can prove to be a challenge, as providers must try to
      determine the substance(s) involved so that the appropriate treatment can be
      initiated. For those patients who are hemodynamically unstable upon presentation,
      it is important to note that supportive care is of the utmost importance, as
      there are few substances that have antidotes available. In these situations,
      lipid emulsion can be considered. This is especially true in the setting of the
      following toxicities: local anesthetics, beta-blockers, calcium channel blockers,
      and the tricyclic antidepressants. Even though lipid emulsion may not be used
      that frequently in the ED, it is important to be aware of its role in the setting
      of toxicological emergencies, how it should be dosed and administered, and the
      necessary safety precautions. 

PMID- 26218484
TI  - Near-Miss Discharge of an Older Adult Male With Central Cord Syndrome.
AB  - Acute traumatic central cord syndrome (ATCCS) occurs in more than 11,000
      individuals annually. A common cause in older adult is a low-velocity
      hypertension neck injury. This article reviews ATCCS from the perspective of an
      older adult who, after a fall at his primary residence, sustained a facial
      laceration. Just prior to discharge, neurological deficits were noted, which
      required further investigation with magnetic resonance imaging. Subsequently, the
      findings required emergent surgical intervention. Emergency nurses should be
      familiar with muscle assessment, deep tendon reflex assessment, and nervous
      system dermatomes. The value of repeating the physical examination prior to
      discharge is discussed. 

PMID- 26218486
TI  - Guidance in Managing Patients Following Radiation Events.
AB  - The threat of a radiological or nuclear disaster is ever-present. If such an
      event were to occur, hospitals would experience a surge of patients and advanced
      practice nurses (APNs) in the emergency department would be expected to
      immediately respond. To mitigate the effects of the disaster, treat patients, and
      prevent self-contamination, APNs must be well informed of nuclear disaster
      management and clinical treatment of radiation exposure. Understanding the
      effects of exposure, pathophysiology of radiation syndromes, and the basic
      tenants of radiation safety is essential for APNs. APNs will be required to
      utilize personal protective equipment during treatment and perform unique tasks
      including disaster triage, decontamination, environmental management, and
      radiological survey while tending to the psychological needs of affected
      individuals. An integrative review of peer-reviewed literature was conducted
      regarding the nursing clinical guidelines for radioactive/nuclear disaster
      management, revealing limited information pertaining to the role of nursing in
      radiological emergency management and decontamination. 

PMID- 26218485
TI  - Assessment and Management of Delirium in Older Adults in the Emergency
      Department: Literature Review to Inform Development of a Novel Clinical Protocol.
AB  - Delirium occurs frequently in older patients in the emergency department (ED), is
      underrecognized, and has potentially serious consequences. Despite its
      seriousness, delirium is frequently missed by emergency providers, and patients
      with unrecognized delirium are often discharged from the ED. Even when it is
      appropriately recognized, managing delirium in older adults poses a significant
      challenge for ED providers. Geriatric delirium is typically caused by the
      interaction of multiple factors, including several that are commonly missed:
      pain, urinary retention, constipation, dehydration, and polypharmacy. Appropriate
      management includes nonpharmacological management with medication intervention
      reserved for emergencies. We have developed a new, comprehensive, evidence-based
      protocol for diagnosis/recognition, management, and disposition of geriatric
      delirium patients in the ED with a focus on identifying and treating commonly
      missed contributing causes. 

PMID- 26218487
TI  - Using a Vulnerability Theoretical Model to Assess the Malignant Hyperthermia
      Susceptible Population: Implications for Advanced Practice Emergency Nurses.
AB  - Malignant hyperthermia (MH) is a high-risk, low-occurrence medical emergency with
      symptoms that include a severe increased rate of metabolic activity and rigid
      skeletal muscles. Clinicians should be knowledgeable and prepared for an MH event
      because it can occur in areas outside the operating room and without anesthetic
      triggers. Patients who have this rare genetic condition may come to the emergency
      department (ED) presenting with symptoms of heat stroke. However, the incidence
      of suspected MH in the ED or other critical care areas is not easily quantifiable
      because clinicians may not report cases to a centralized registry. The purpose of
      this article is to describe the MH-susceptible vulnerable population, to apply a
      vulnerability theoretical model to assess patients and families, to identify
      strategies for health promotion to reduce vulnerability, and to discuss how
      advanced practice nurses who specialize in emergency care can help decrease the
      vulnerability of MH-susceptible patients and families. By using a vulnerability
      model to assess the MH-susceptible population, nurses can effectively sort out
      strategies to prevent poor patient outcomes related to MH and promote health for
      this high-risk population. Measuring accurate core temperatures, applying
      effective cooling methods, and administering dantrolene are key concepts in
      caring for a patient who is experiencing an MH event. Advanced practice emergency
      nurses can participate in reducing vulnerability for this population by applying
      the Emergency Nurses Association Clinical Nurse Specialist competencies to MH
      related vulnerabilities. Enhancing preparedness, evaluating and coordinating
      education programs, advocating for report submissions to the North American
      Malignant Hyperthermia Registry, and assessing opportunities for community
      collaboration are among the strategies discussed for reducing vulnerability for
      the MH-susceptible population. 

PMID- 26218488
TI  - The Effect of a Clinical Practice Guideline for Acute Pelvic Pain on Length of
      Stay in the Emergency Department.
AB  - Length of stay (LOS) is a key measure of emergency department (ED) efficiency and
      a marker of overcrowding. The use of clinical practice guidelines (CPGs) has been
      shown to decrease the time spent in the ED. The objective of this study was to
      determine whether the utilization of a CPG for evaluation of acute pelvic pain in
      the ED would reduce patient LOS. This before-and-after study was conducted at a
      large urban Level II ED over the course of 2 years. A retrospective review of 134
      electronic patient records: 67 charts prior to protocol implementation; 67 after
      implementation of a CPG for the evaluation of acute pelvic pain. Length of stay
      was based on the time from triage to discharge. The before-and-after protocol
      groups were compared using an independent-samples t test. Length of stay was
      actually increased in the protocol group (n = 67, M = 5:16, SD = 4:14 [hr:min]; p
      = 0.092). The use of diagnostic imaging was associated with longer LOS, varying
      with the specific imaging performed. Because of financial restructuring, the
      radiology unit reduced the availability of in-house sonography to 9:00 a.m.-5:00
      p.m., Monday through Friday, which also possibly affected the LOS. Of
      significance was the willingness of the health care providers to utilize the CPG
      (86%). Time of day, availability of in-house ultrasound, and individual provider
      judgment influence ED LOS and subsequent imaging performed. Future research is
      necessary to determine how these and other factors can be incorporated into a
      model for predicting LOS, reducing provider disparities, and ensuring patient
      safety. 

PMID- 26218489
TI  - Advanced Nurse Practitioner Educational Needs for Safe and Efficient Radiological
      Imaging.
AB  - This study evaluated perceived knowledge and educational preparedness of advanced
      practice nurses (APNs) in the area of radiological imaging, including awareness
      and utilization of the American College of Radiology Appropriateness Criteria
      (ACR-AC). Previous studies have found a need for further education in
      radiological imaging for medical students, residents, and hospitalists; however,
      little to no research has been done to assess such knowledge and educational
      preparedness among APNs. An e-mail link to a researcher-developed questionnaire
      was sent to Florida licensed APNs. Statistical analysis used descriptive,
      parametric, and nonparametric methods including frequencies, percentages, and
      Mann-Whitney U statistics. Florida licensed APNs (n = 905) from 175 educational
      programs and 10 specialty areas responded to the questionnaire; 75.9% (n = 681)
      had never heard of the ACR-AC. Years of experience and training in acute care
      specialties increased perceived competency in ordering radiological tests.
      Results among APNs were similar to those reported from physician studies, and
      92.3% of respondents (n = 829) stated that additional APN imaging education would
      be beneficial. These findings highlight the importance of incorporating more
      radiological imaging information into APN education, which could lead to a
      reduction in overall costs and improvement in perceived competence and knowledge
      of appropriate imaging utilization. 

PMID- 26218491
TI  - Medical Insecurity.

PMID- 26218492
TI  - The Participation of HPV-Vaccinated Women in a National Cervical Screening
      Program: Population-Based Cohort Study.
AB  - BACKGROUND: Concerns have been raised that HPV-vaccination might affect women's
      cervical screening behavior. We therefore investigated the association between
      opportunistic HPV-vaccination and attendance after invitation to cervical
      screening. METHODS: A cohort of all women resident in Sweden, born 1977-1987
      (N=629,703), and invited to cervical screening, was followed October 2006 -
      December 2012. Invitations to screening were identified via the National Quality
      Register for Cervical Cancer Prevention, as was the primary outcome of a
      registered smear. Vaccination status was obtained from two nationwide health data
      registers. Hazard ratios (HR) were estimated using Cox regression adjusted for
      age, education level and income (HRadj). Women were individually followed for up
      to 6 years, of which the first and second screening rounds were analyzed
      separately. RESULTS: Screening attendance after three years of follow-up was 86%
      in vaccinated women (N=4,897) and 75% in unvaccinated women (N=625,804). The
      crude HR of screening attendance in vaccinated vs. unvaccinated women was 1.31
      (95% CI 1.27-1.35) in the first screening round. Adjustment for education and
      income reduced but did not erase this difference (HRadj=1.09, 95% CI 1.05-1.13).
      In the second screening round, attendance was likewise higher in HPV-vaccinated
      women (crude HR=1.26, 95% CI 1.21-1.32; HRadj=1.15, 95% CI 1.10-1.20).
      CONCLUSIONS: HPV-vaccination is so far associated with equal or higher attendance
      to cervical screening in Sweden in a cohort of opportunistically vaccinated young
      women. Most but not all of the difference in attendance was explained by
      socioeconomic differences between vaccinated and unvaccinated women. HPV vaccine
      effectiveness studies should consider screening attendance of HPV-vaccinated
      women when assessing incidence of screen-detected cervical lesions.

PMID- 26218493
TI  - Ultrasound in the diagnosis and management of pleural effusions.
AB  - We review the literature on the use of point-of-care ultrasound to evaluate and
      manage pleural effusions. Point-of-care ultrasound is more sensitive than
      physical exam and chest radiography to detect pleural effusions, and avoids many
      negative aspects of computerized tomography. Additionally, point-of-care
      ultrasound can assess pleural fluid volume and character, revealing possible
      underlying pathologies and guiding management. Thoracentesis performed with
      ultrasound guidance has lower risk of pneumothorax and bleeding complications.
      Future research should focus on the clinical effectiveness of point-of-care
      ultrasound in the routine management of pleural effusions and how new
      technologies may expand its clinical utility.

PMID- 26218495
TI  - Facile and Quantitative Synthesis of a Poly(ethylene glycol)-b-Poly(l-arginine)
      Block Copolymer and Its Use for the Preparation of Polyion Complex Micelles with
      Polyanions for Biomedical Applications.
AB  - Though l-arginine-containing polymers show versatile biological functions, a
      precisely controlled synthesis of poly(ethylene glycol)-b-poly(l-arginine) (PEG-b
      PArg) block copolymers has not been reported. Here, an effective method for the
      synthesis of PEG-b-PArg block copolymers is developed. In order to obtain PEG-b
      PArg, a two-step reaction, i.e., synthesis of PEG-b-poly(l-ornithine) is
      employed, followed by guanidinylation with N,N'-bis(tert-butoxycarbonyl)-1H
      pyrazole-1-carboxamidine. This procedure quantitatively converts amino groups to
      guanidium groups at the side chains of peptide segments under mild conditions.
      Polyion complex (PIC) micelles are prepared by mixing the positively charged PEG
      b-PArg with negatively charged homo-polyelectrolytes such as hyaluronic acid (HA)
      or chondroitin sulfate C (CS). PIC micelles prepared with CS show a higher
      stability than those prepared with HA, probably due to strong interactions
      between guanidium cations in PEG-b-PArg and carboxylate/sulfate in CS. Thus, PIC
      micelles containing PArg are a potentially effective arginine carrier for the
      development of in vivo therapeutic applications for various diseases related to
      nitric oxide, which is generated from inducible nitric oxide synthase in
      macrophages using l-arginine as a substrate.

PMID- 26218494
TI  - Have We Improved Pain Control in Cancer Patients? A Multicenter Study of
      Ambulatory and Hospitalized Cancer Patients.
AB  - BACKGROUND: Pain in cancer patients is recognized as a major health problem, yet
      few studies of both inpatient and outpatient populations have been carried out.
      OBJECTIVE: The study objective was to assess the frequency, type, and
      characteristics of pain in adult cancer patients, including both inpatients and
      outpatients. METHODS: This cross-sectional study involved 1064 adult cancer
      patients (437 outpatients and 627 inpatients) from 44 hospitals and/or long-term
      care centers in Catalonia, Spain. Cancer patients suffering from pain of any
      etiology for >=2 weeks and/or under analgesic treatment >=2 weeks were enrolled.
      Demographic and pain data were collected. The Spanish version of the Brief Pain
      Inventory was used to assess pain. RESULTS: Pain frequency was 55.3%. Pain was
      less frequent in outpatients than inpatients (41.6% versus 64.7%; p<0.001),
      although median pain duration was longer in outpatients (20 versus 6 weeks;
      p<0.001). Pain was assessable in 333 patients, and intensity was similar in both
      out- and inpatients; however, outpatients reported less improvement, less pain
      interference with daily life, and less pain related to the cancer per se. In both
      groups, patients with multiple myeloma (73%), breast (65%), and lung cancer (61%)
      were most likely to report pain. CONCLUSIONS: Pain in cancer patients, both
      ambulatory and hospitalized, remains a challenge for health care professionals,
      health administrators, and stakeholders. Our study reveals the high level of pain
      and distress that cancer patients continue to suffer, a problem that is
      particularly notable in outpatients due to the intensity and duration of the
      pain.

PMID- 26218496
TI  - Emergent features and perceptual objects: re-examining fundamental principles in
      analogical display design.
AB  - Two sets of design principles for analogical visual displays, based on the
      concepts of emergent features and perceptual objects, are described. An
      interpretation of previous empirical findings for three displays (bar graph,
      polar graphic, alphanumeric) is provided from both perspectives. A fourth display
      (configural coordinate) was designed using principles of ecological interface
      design (i.e. direct perception). An experiment was conducted to evaluate
      performance (accuracy and latency of state identification) with these four
      displays. Numerous significant effects were obtained and a clear rank ordering of
      performance emerged (from best to worst): configural coordinate, bar graph,
      alphanumeric and polar graphic. These findings are consistent with principles of
      design based on emergent features; they are inconsistent with principles based on
      perceptual objects. Some limitations of the configural coordinate display are
      discussed and a redesign is provided. Practitioner Summary: Principles of
      ecological interface design, which emphasise the quality of very specific
      mappings between domain, display and observer constraints, are described; these
      principles are applicable to the design of all analogical graphical displays.

PMID- 26218497
TI  - Interaction of Cytotoxic and Cytoprotective Bile Acids with Model Membranes:
      Influence of the Membrane Composition.
AB  - To understand the role of bile acids (BAs) in cell function, many authors have
      investigated their effect on biomembrane models which are less complex systems,
      but there are still many open questions. The present study aims to contribute for
      the deepening of the knowledge of the interaction between BAs and model
      membranes, in particular, focusing on the effect of BA mixtures. The cytotoxic
      deoxycholic acid (DCA), the cytoprotective ursodeoxycholic acid (UDCA), and the
      equimolar mixture (DCA + UDCA) were investigated. Monolayers and liposomes were
      taken as model membranes with two lipid compositions: an equimolar mixture of 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM), and
      cholesterol (Chol)) traditionally associated with the formation of lipid rafts
      and an equimolar POPC/SM binary mixture. The obtained results showed that DCA
      causes the fluidization of monolayers and bilayers, leading to the eventual
      rupture of POPC/SM liposomes at high concentration. UDCA may provide a
      stabilization of POPC/SM membranes but has a negligible effect on the Chol
      containing liposomes. In the case of equimolar mixture DCA/UDCA, the interactions
      depend not only on the lipid composition but also on the design of the
      experiment. The BA mixture has a greater impact on the monolayers than do pure
      BAs, suggesting a cooperative DCA-UDCA interaction that enhances the penetration
      of UDCA in both POPC/SM and POPC/SM/Chol monolayers. For the bilayers, the
      presence of UDCA in the mixture decreases the disturbing effect of DCA. 

PMID- 26218498
TI  - Surgery of the thyroid: recent developments and perspective.
AB  - In the past century, thyroid surgery has benefited from physiological and
      technical revolutions. In the early 1900s, the most important aspect of
      thyroidectomy was the volume resected, without knowledge of exactly what was
      removed and if there were important structures around the thyroid gland. The main
      indications were respiratory problems for tracheal compression and the death rate
      was greater than 36% due to bleeding, infections, unrecognised bilateral
      recurrent laryngeal nerve lesions and unrecognised severe hypocalcaemia leading
      to tetany. At some point this surgery was, therefore, banned in some countries
      such as France and the United States. Today, thyroid surgery is a common surgery:
      about 45,000 thyroidectomies are performed per year in France, 60,000 in Germany
      and 4,000 in Switzerland. Thyroid surgery has become very safe with a mortality
      of almost 0% and a very low complication rate. In our centre, the number of
      thyroidectomies has more than tripled in the last decade. There are many
      indications leading to thyroid surgery, but the three main indications covering
      90% of the interventions are cancer (or suspected cancer), hyperthyroidism and
      size / volume / intrathoracic goitres. In this paper, we highlight some
      historical points, describe important knowledge and technical improvements made
      during the last century and give our opinion on expected evolution in this field
      for the near future.

PMID- 26218499
TI  - Accuracy of a Simplified Glucose Measurement Device--The HemoCue Glucose 201RT.
AB  - BACKGROUND: Easily available, accurate glucose recordings are important when
      screening for and managing people with diabetes. The photometric HemoCue((r))
      (Angelholm, Sweden) Glucose 201+ system, which delivers lab-comparable glucose
      recordings, has the drawback that its microcuvettes must be delivered and stored
      at 4-8 degrees C. A newly developed system, HemoCue Glucose 201RT, has
      microcuvettes that can be stored at room temperature. SUBJECTS AND METHODS:
      Participants (n=444; 18-80 years old) in the EUROASPIRE IV survey, all with
      coronary artery disease, some with known diabetes, were investigated. Plasma
      glucose recordings, fasting in all participants and postprandial in the majority,
      were simultaneously recorded with both pieces of equipment. Congruence was
      expressed as median absolute difference and median absolute relative difference
      between the two sets of equipment and also compared according to the
      International Organization for Standardization (ISO) 15197:2013 criteria.
      Clinical accuracy was calculated with Clarke error grid analysis and cross
      tabulated while considering different glucose categories (normal, impaired
      glucose tolerance, and diabetes). RESULTS: The median absolute difference between
      the two devices was +0.1 mmol/L, and the median absolute relative difference was
      +5.4%. This also corresponded with the ISO criteria. In the Clarke error grid,
      99.8% ended up in Zones A and B, and 90% of the glucose values in the cross-table
      allocated the participant to the same glucose category. CONCLUSIONS: The HemoCue
      Glucose 201RT system is accurate, with small nonsystematic deviations, when
      compared with the commonly used HemoCue Glucose 201+. It is predicted that the
      HemoCue Glucose 201RT, which is more user friendly, will be a preferred
      alternative to the HemoCue Glucose 201+.

PMID- 26218500
TI  - SYSTEMIC INTERLEUKIN 1beta INHIBITION IN PROLIFERATIVE DIABETIC RETINOPATHY: A
      Prospective Open-Label Study Using Canakinumab.
AB  - PURPOSE: To evaluate the effect of systemic interleukin 1beta inhibition using
      canakinumab (Ilaris) on retinal neovascularizations in proliferative diabetic
      retinopathy. METHODS: Patients with proliferative diabetic retinopathy were
      enrolled in a prospective uncontrolled pilot study. Canakinumab (150 mg) was
      given 3 times subcutaneously. The primary end point was the change in the area of
      neovascularization from baseline to Week 24. Secondary end points were the change
      in retinal edema measured and best-corrected visual acuity (BCVA), as well as
      systemic safety evaluation, HbA1c, and systemic inflammatory parameters. RESULTS:
      Systemic canakinumab treatment was well tolerated. None of the 8 eyes showed
      progression of neovascularizations within 24 weeks. Their mean size remained
      unchanged comparing 0.60 mm at baseline with 0.62 mm at Week 24 (P = 0.944).
      Median BCVA remained stable with 80 ETDRS letters at baseline and 82 ETDRS
      letters at Week 24. A not statistically significant reduction in retinal edema
      was detectable for the foveal central subfield thickness (mean, 313-295 MUm).
      Mean HbA1c improved significantly from 7.92% to 7.30% within the 24 weeks (P =
      0.046). Systemic inflammatory parameters remained overall unchanged. CONCLUSION:
      Systemic canakinumab showed no change in neovascularizations in diabetic
      retinopathy. Promising effects were seen on diabetic macular edema.

PMID- 26218501
TI  - Tunable Dipole Surface Plasmon Resonances of Silver Nanoparticles by Cladding
      Dielectric Layers.
AB  - The tunability of surface plasmon resonance can enable the highest degree of
      localised surface plasmon enhancement to be achieved, based on the emitting or
      absorbing wavelength. In this article, tunable dipole surface plasmon resonances
      of Ag nanoparticles (NPs) are realized by modification of the SiO2 dielectric
      layer thicknesses. SiO2 layers both beneath and over the Ag NPs affected the
      resonance wavelengths of local surface plasmons (LSPs). By adjusting the SiO2
      thickness beneath the Ag NPs from 5 nm to 20 nm, the dipole surface plasmon
      resonances shifted from 470 nm to 410 nm. Meanwhile, after sandwiching the Ag NPs
      by growing SiO2 before NPs fabrication and then overcoating the NPs with various
      SiO2 thicknesses from 5 nm to 20 nm, the dipole surface plasmon resonances
      changed from 450 nm to 490 nm. The SiO2 cladding dielectric layer can tune the Ag
      NP surface charge, leading to a change in the effective permittivity of the
      surrounding medium, and thus to a blueshift or redshift of the resonance
      wavelength. Also, the quadrupole plasmon resonances were suppressed by the SiO2
      cladding layer because the dielectric SiO2 can suppress level splitting of
      surface plasmon resonances caused by the Ag NP coupling effect. 

PMID- 26218502
TI  - No changes in N-terminal pro-brain natriuretic peptide in a longitudinal cohort
      of patients with systemic sclerosis-associated pulmonary arterial hypertension on
      therapy with bosentan.
AB  - AIM: The aim of this study was to evaluate N-terminal pro-brain natriuretic
      peptide (NT-proBNP) in patients with systemic sclerosis (SSc)-associated
      pulmonary arterial hypertension (PAH) and changes after therapy with bosentan.
      METHOD: Twenty-one patients with SSc-PAH on bosentan therapy were enrolled. PAH
      was diagnosed by right heart catheterization. NT-proBNP levels, 6-min walking
      test (6MWT), Doppler echocardiography to estimated systolic pulmonary arterial
      pressure (sPAP), New York Heart Association (NYHA) functional class for dyspnea
      and carbon monoxide lung diffusion capacity (DLco) were recorded at baseline, and
      after 1 and 2 years. Fifty-two SSc patients without PAH were also evaluated as
      controls. RESULTS: NT-proBNP plasma levels were significantly higher in SSc-PAH
      at 385 pg/mL (SD +/- 427) than in SSc without PAH and 72 pg/mL (SD +/- 52, P <
      0.001) at baseline, but did not significantly change following bosentan therapy
      at 1 year (330 pg/mL [SD +/- 291] and 2 years (374 pg/mL [SD +/- 291]). However,
      NYHA class significantly improved at 2 years (P = 0.01) as well as 6MWT (P =
      0.04). NT-proBNP levels were positively correlated only with sPAP but not with
      DLco, NYHA class or 6MWT. CONCLUSIONS: NT-proBNP levels were found to be
      significantly higher in SSc-PAH at baseline. Serial assessment of NT-proBNP in
      SSc-PAH patients on bosentan therapy showed no relation to the clinical
      improvement. This suggests that NT-proBNP may lack 'sensitivity to change', but
      further studies are warranted to assess the role of NT-proBNP as a biomarker of
      the therapeutic response in larger cohorts of SSc patients.

PMID- 26218503
TI  - Thickness-Dependent Hydrophobicity of Epitaxial Graphene.
AB  - This article addresses the much debated question whether the degree of
      hydrophobicity of single-layer graphene (1LG) is different from that of double
      layer graphene (2LG). Knowledge of the water affinity of graphene and its spatial
      variations is critically important as it can affect the graphene properties as
      well as the performance of graphene devices exposed to humidity. By employing
      chemical force microscopy with a probe rendered hydrophobic by functionalization
      with octadecyltrichlorosilane (OTS), the adhesion force between the probe and
      epitaxial graphene on SiC has been measured in deionized water. Owing to the
      hydrophobic attraction, a larger adhesion force was measured on 2LG Bernal
      stacked domains of graphene surfaces, thus showing that 2LG is more hydrophobic
      than 1LG. Identification of 1LG and 2LG domains was achieved through Kelvin probe
      force microscopy and Raman spectral mapping. Approximate values of the adhesion
      force per OTS molecule have been calculated through contact area analysis.
      Furthermore, the contrast of friction force images measured in contact mode was
      reversed to the 1LG/2LG adhesion contrast, and its origin was discussed in terms
      of the likely water depletion over hydrophobic domains as well as deformation in
      the contact area between the atomic force microscope tip and 1LG. 

PMID- 26218504
TI  - Modelling the Noise-Robustness of Infants' Word Representations: The Impact of
      Previous Experience.
AB  - During language acquisition, infants frequently encounter ambient noise. We
      present a computational model to address whether specific acoustic processing
      abilities are necessary to detect known words in moderate noise--an ability
      attested experimentally in infants. The model implements a general purpose speech
      encoding and word detection procedure. Importantly, the model contains no
      dedicated processes for removing or cancelling out ambient noise, and it can
      replicate the patterns of results obtained in several infant experiments. In
      addition to noise, we also addressed the role of previous experience with
      particular target words: does the frequency of a word matter, and does it play a
      role whether that word has been spoken by one or multiple speakers? The
      simulation results show that both factors affect noise robustness. We also
      investigated how robust word detection is to changes in speaker identity by
      comparing words spoken by known versus unknown speakers during the simulated
      test. This factor interacted with both noise level and past experience, showing
      that an increase in exposure is only helpful when a familiar speaker provides the
      test material. Added variability proved helpful only when encountering an unknown
      speaker. Finally, we addressed whether infants need to recognise specific words,
      or whether a more parsimonious explanation of infant behaviour, which we refer to
      as matching, is sufficient. Recognition involves a focus of attention on a
      specific target word, while matching only requires finding the best
      correspondence of acoustic input to a known pattern in the memory. Attending to a
      specific target word proves to be more noise robust, but a general word matching
      procedure can be sufficient to simulate experimental data stemming from young
      infants. A change from acoustic matching to targeted recognition provides an
      explanation of the improvements observed in infants around their first birthday.
      In summary, we present a computational model incorporating only the processes
      infants might employ when hearing words in noise. Our findings show that a
      parsimonious interpretation of behaviour is sufficient and we offer a formal
      account of emerging abilities.

PMID- 26218505
TI  - Studies of a pyridino-crown ether-based chiral stationary phase on the
      enantioseparation of biogenic chiral aralkylamines and alpha-amino acid esters by
      high-performance liquid chromatography.
AB  - This paper reports the enantioseparation ability of a pyridino-18-crown-6 ether
      based chiral stationary phase [(S,S)-CSP-1]. The enantiomeric discrimination of
      chiral stationary phase (S,S)-CSP-1 was evaluated by HPLC using the mixtures of
      enantiomers of various protonated primary aralkylamines [1-phenylethylamine
      hydrogen perchlorate (PEA), 2,3-dihydro-1H-inden-1-amine (1-aminoindan), 2,2'
      (1,2-diaminoethane-1,2-diyl) diphenol (HPEN)] and perchlorate salts of alpha
      amino acid esters [alanine benzyl ester (Ala-OBn), phenylalanine benzyl ester
      (Phe-OBn), phenylalanine methyl ester (Phe-OMe), phenylglycine methyl ester
      (PhGly-OMe), glutamic acid dibenzyl ester (Glu-diOBn), and valine benzyl ester
      (Val-OBn)]. The best enantioseparation was achieved in the case of PEA. The high
      enantioselectivity was rationalized by the strong pi-pi interaction of the
      extended pi system of the aryl-substituted pyridine unit.

PMID- 26218506
TI  - A selective and sensitive method based on UPLC-MS/MS for quantification of
      momordin Ic in rat plasma: application to a pharmacokinetic study.
AB  - A selective and sensitive method was developed and validated based on ultra
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). This
      method was applied to quantify momordin Ic in rat plasma. Chromatographic
      separation was performed on a Hypersil GOLD HPLC C18 column (150mm*4.6mm, 5MUm)
      using an isocratic mobile phase of acetonitrile/water (80:20, v/v) at a flow rate
      of 0.6mL/min. An electrospray ionization source was applied and operated in
      negative ion mode; selected reaction monitoring (SRM) mode was used for
      quantification by monitoring the precursor-to-product ion transitions of m/z
      763.4->m/z 455.3 for momordin Ic, and m/z 649.4->m/z 487.3 for IS. Calibration
      curves showed good linearity over the range of 22.0-2200ng/mL for momordin Ic in
      rat plasma. The developed method was applied to a pharmacokinetic study of
      momordin Ic in rats after single intravenous doses at 0.52, 1.56, and 4.67mg/kg.
      The elimination half-life (t1/2) values were 1.22+/-0.39, 1.14+/-0.10, and 1.83+/
      0.39h, respectively. The plasma concentration at 2min (C2min) and area under the
      curve (AUC) for the intravenous doses of momordin Ic were approximately dose
      proportional.

PMID- 26218508
TI  - Editorial Comment for Ibrahim et al.

PMID- 26218507
TI  - Evaluation of candidate vaccine approaches for MERS-CoV.
AB  - The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a
      cause of severe respiratory disease highlights the need for effective approaches
      to CoV vaccine development. Efforts focused solely on the receptor-binding domain
      (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody
      (NAb) responses. Here we show that immunogens based on full-length S DNA and S1
      subunit protein elicit robust serum-neutralizing activity against several MERS
      CoV strains in mice and non-human primates. Serological analysis and isolation of
      murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and,
      non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were
      demonstrated by solving the atomic structure of a NAb-RBD complex, through
      sequencing of neutralization escape viruses and by constructing MERS-CoV S
      variants for serological assays. Immunization of rhesus macaques confers
      protection against MERS-CoV-induced radiographic pneumonia, as assessed using
      computerized tomography, supporting this strategy as a promising approach for
      MERS-CoV vaccine development. 

PMID- 26218509
TI  - Motor Coordination Difficulties in Extremely Low Birth Weight Survivors Across
      Four Decades.
AB  - OBJECTIVE: To compare levels of motor coordination difficulties in a cohort of
      extremely low birth weight (ELBW; <1000 g) survivors and normal birth weight
      (NBW) controls from childhood until age 36. The stability of motor coordination
      in ELBW and NBW adults from their 20s to their 30s was also assessed. METHODS:
      This study uses a prospectively followed population-based birth cohort of ELBW
      survivors born between 1977 and 1982 in Ontario, Canada, to compare motor
      coordination at age 8, age 22 to 26, and age 29 to 36 in ELBW survivors relative
      to a matched group of NBW controls across a number of different measures.
      RESULTS: After adjusting for neurosensory impairment, ELBW survivors had
      significantly higher levels of motor coordination difficulties than their NBW
      counterparts at age 8, 22 to 26, and 29 to 36. Self-reported motor coordination
      remained relatively stable from age 22 to 26 to age 29 to 36 in both groups.
      CONCLUSIONS: ELBW survivors display higher levels of motor coordination
      difficulties than NBW controls in childhood through their mid 30s. Motor
      coordination seems to be stable from age 22 to 36 in both groups, suggesting that
      the presence of motor problems in ELBW survivors can have important implications
      for functional outcomes in adulthood.

PMID- 26218510
TI  - EphA2 as a Diagnostic Imaging Target in Glioblastoma: A Positron Emission
      Tomography/Magnetic Resonance Imaging Study.
AB  - Noninvasive imaging is a critical technology for diagnosis, classification, and
      subsequent treatment planning for patients with glioblastoma. It has been shown
      that the EphA2 receptor tyrosine kinase (RTK) is overexpressed in a number of
      tumors, including glioblastoma. Expression levels of Eph RTKs have been linked to
      tumor progression, metastatic spread, and poor patient prognosis. As EphA2 is
      expressed at low levels in normal neural tissues, this protein represents an
      attractive imaging target for delineation of tumor infiltration, providing an
      improved platform for image-guided therapy. In this study, EphA2-4B3, a
      monoclonal antibody specific to human EphA2, was labeled with 64Cu through
      conjugation to the chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA).
      The resulting complex was used as a positron emission tomography (PET) tracer for
      the acquisition of high-resolution longitudinal PET/magnetic resonance images.
      EphA2-4B3-NOTA-64Cu images were qualitatively and quantitatively compared to the
      current clinical standards of [18F]FDOPA and gadolinium (Gd) contrast-enhanced
      MRI. We show that EphA2-4B3-NOTA-64Cu effectively delineates tumor boundaries in
      three different mouse models of glioblastoma. Tumor to brain contrast is
      significantly higher in EphA2-4B3-NOTA-64Cu images than in [18F]FDOPA images and
      Gd contrast-enhanced MRI. Furthermore, we show that nonspecific uptake in the
      liver and spleen can be effectively blocked by a dose of nonspecific (isotype
      control) IgG.

PMID- 26218514
TI  - Side flankers produce less crowding, but only for letters.
AB  - Identification of isolated and crowded letter (B, D, F, G, K, N, L, S, T) and
      symbol stimuli (%, /, ?, @, }, <, L, S, MU) was examined across the visual field
      in a two-alternative forced-choice match-to-sample task (2AFC-MTS). During
      isolated presentation, identification accuracy did not differ between the two
      stimulus types. Identification rates for the central characters within the three
      character strings were higher for letters than for symbols at the horizontal and
      vertical meridian (Experiment 1), and at diagonal locations (Experiment 2).
      However, this reduction of parafoveal letter crowding was present in horizontally
      but not in vertically oriented strings of stimuli. The same pattern of results
      was replicated in the periphery of the visual field (Experiment 3). The obtained
      results are in agreement with the proposition that the receptive fields of letter
      detectors are modified during reading acquisition, in order to support efficient
      letter identification (Tydgat & Grainger, 2009). However, the pervasive presence
      of the effect across the visual field suggests that it could originate from a non
      retinotopic stage of visual processing. 

PMID- 26218512
TI  - Advances in lupus genetics.
AB  - PURPOSE OF REVIEW: The field of systemic lupus erythematosus (SLE) genetics has
      been advancing rapidly in recent years. This review will summarize recent
      advances in SLE genetics. RECENT FINDINGS: Genome-wide-association and follow-up
      studies have greatly expanded the list of associated polymorphisms, and much
      current work strives to integrate these polymorphisms into immune system biology
      and the pathogenic mediators involved in the disease. This review covers some
      current areas of interest, including genetic studies in non-European SLE patient
      populations, studies of pathogenic immune system subphenotypes such as type I
      interferon and autoantibodies, and a rapidly growing body of work investigating
      the functional consequences of the genetic polymorphisms associated with SLE.
      SUMMARY: These studies provide a fascinating window into human SLE disease
      biology. As the work proceeds from genetic association signal to altered human
      biology, we move closer to tailoring interventions based upon an individual's
      genetic substrate.

PMID- 26218515
TI  - How short- and long-run aspirations impact search and choice in decisions from
      experience.
AB  - To what extent do people adapt their information search policies and subsequent
      decisions to the long- and short-run consequences of choice environments? To
      address this question, we investigated exploration and exploitation policies in
      choice environments that involved single or multiple plays. We further compared
      behavior in these environments with behavior in the standard sampling paradigm.
      Frequently used in research on decision from experience, this paradigm does not
      explicitly implement the choice in terms of the short or long run. Results showed
      that people searched more in the multi-play environment than in the single-play
      environment. Moreover, the substantial search effort in the multi-play
      environment was conducive to choices consistent with expected value maximization,
      whereas the lesser search effort in the single-play environment was compatible
      with the goal of maximizing the chance of winning something. Furthermore, choice
      and search behaviors in the sampling paradigm predominantly echoed those observed
      in the single-play environment. This suggests that, when not instructed
      otherwise, participants in the sampling paradigm appear to favor search and
      choice strategies that embody short-run aspirations. Finally, the present
      findings challenge the revealed preference approach in decisions from experience,
      while also suggesting that information search may be an important and potentially
      even better signal of preference or aspirations than choice. 

PMID- 26218516
TI  - Serial-order learning impairment and hypersensitivity-to-interference in
      dyscalculia.
AB  - In the context of heterogeneity, the different profiles of dyscalculia are still
      hypothetical. This study aims to link features of mathematical difficulties to
      certain potential etiologies. First, we wanted to test the hypothesis of a serial
      order learning deficit in adults with dyscalculia. For this purpose we used a
      Hebb repetition learning task. Second, we wanted to explore a recent hypothesis
      according to which hypersensitivity-to-interference hampers the storage of
      arithmetic facts and leads to a particular profile of dyscalculia. We therefore
      used interfering and non-interfering repeated sequences in the Hebb paradigm. A
      final test was used to assess the memory trace of the non-interfering sequence
      and the capacity to manipulate it. In line with our predictions, we observed that
      people with dyscalculia who show good conceptual knowledge in mathematics but
      impaired arithmetic fluency suffer from increased sensitivity-to-interference
      compared to controls. Secondly, people with dyscalculia who show a deficit in a
      global mathematical test suffer from a serial-order learning deficit
      characterized by a slow learning and a quick degradation of the memory trace of
      the repeated sequence. A serial-order learning impairment could be one of the
      explanations for a basic numerical deficit, since it is necessary for the number
      word sequence acquisition. Among the different profiles of dyscalculia, this
      study provides new evidence and refinement for two particular profiles. 

PMID- 26218517
TI  - Health, Health Inequality, and Cost Impacts of Annual Increases in Tobacco Tax:
      Multistate Life Table Modeling in New Zealand.
AB  - BACKGROUND: Countries are increasingly considering how to reduce or even end
      tobacco consumption, and raising tobacco taxes is a potential strategy to achieve
      these goals. We estimated the impacts on health, health inequalities, and health
      system costs of ongoing tobacco tax increases (10% annually from 2011 to 2031,
      compared to no tax increases from 2011 ["business as usual," BAU]), in a country
      (New Zealand) with large ethnic inequalities in smoking-related and
      noncommunicable disease (NCD) burden. METHODS AND FINDINGS: We modeled 16 tobacco
      related diseases in parallel, using rich national data by sex, age, and
      ethnicity, to estimate undiscounted quality-adjusted life-years (QALYs) gained
      and net health system costs over the remaining life of the 2011 population (n =
      4.4 million). A total of 260,000 (95% uncertainty interval [UI]: 155,000-419,000)
      QALYs were gained among the 2011 cohort exposed to annual tobacco tax increases,
      compared to BAU, and cost savings were US$2,550 million (95% UI: US$1,480 to
      US$4,000). QALY gains and cost savings took 50 y to peak, owing to such factors
      as the price sensitivity of youth and young adult smokers. The QALY gains per
      capita were 3.7 times greater for Maori (indigenous population) compared to non
      Maori because of higher background smoking prevalence and price sensitivity in
      Maori. Health inequalities measured by differences in 45+ y-old standardized
      mortality rates between Maori and non-Maori were projected to be 2.31% (95% UI:
      1.49% to 3.41%) less in 2041 with ongoing tax rises, compared to BAU. Percentage
      reductions in inequalities in 2041 were maximal for 45-64-y-old women (3.01%). As
      with all such modeling, there were limitations pertaining to the model structure
      and input parameters. CONCLUSIONS: Ongoing tobacco tax increases deliver sizeable
      health gains and health sector cost savings and are likely to reduce health
      inequalities. However, if policy makers are to achieve more rapid reductions in
      the NCD burden and health inequalities, they will also need to complement tobacco
      tax increases with additional tobacco control interventions focused on cessation.

PMID- 26218519
TI  - Synthesis and Reactivity Profile of Ylidenemalononitrile Enamines and Their Ester
      Analogs Towards Electrophiles and Nucleophiles.
AB  - Herein, we describe the synthesis and reactivity of enamines derived from
      ylidenemalononitriles and ylidenecyanoacetates. The enamine scope was expanded by
      (1) increasing yields of aldehyde-derived ylidenemalononitriles, (2)
      incorporating silyl functionalities, and (3) using other amide acetals to expand
      the substitution patterns of pyridines resulting from enamine cyclization. In
      addition, methods to produce alpha-pyrones and polysubstituted pyridines from
      both ylidenemalononitriles and ylidenecyanoacetates are described. 

PMID- 26218518
TI  - Polymorphisms of the UCP2 Gene Are Associated with Glomerular Filtration Rate in
      Type 2 Diabetic Patients and with Decreased UCP2 Gene Expression in Human Kidney.
AB  - INTRODUCTION: Uncoupling protein 2 (UCP2) reduces production of reactive oxygen
      species (ROS) by mitochondria. ROS overproduction is one of the major
      contributors to the pathogenesis of chronic diabetic complications, such as
      diabetic kidney disease (DKD). Thus, deleterious polymorphisms in the UCP2 gene
      are candidate risk factors for DKD. In this study, we investigated whether UCP2 
      866G/A, Ala55Val and Ins/Del polymorphisms were associated with DKD in patients
      with type 2 diabetes mellitus (T2DM), and whether they had an effect on UCP2 gene
      expression in human kidney tissue biopsies. MATERIALS AND METHODS: In a case
      control study, frequencies of the UCP2 -866G/A, Ala55Val and Ins/Del
      polymorphisms as well as frequencies of the haplotypes constituted by them were
      analyzed in 287 T2DM patients with DKD and 281 T2DM patients without this
      complication. In a cross-sectional study, UCP2 gene expression was evaluated in
      42 kidney biopsy samples stratified according to the presence of the UCP2 mutated
      -866A/55Val/Ins haplotype. RESULTS: In the T2DM group, multivariate logistic
      regression analysis showed that the -866A/55Val/Ins haplotype was an independent
      risk factor for DKD (OR = 2.136, 95% CI 1.036-4.404), although neither genotype
      nor allele frequencies of the individual polymorphisms differed between case and
      control groups. Interestingly, T2DM patients carrying the mutated haplotype
      showed decreased estimated glomerular filtration rate (eGFR) when compared to
      subjects with the reference haplotype (adjusted P= 0.035). In kidney biopsy
      samples, UCP2 expression was significantly decreased in UCP2 mutated haplotype
      carriers when compared to kidneys from patients with the reference haplotype
      (0.32 +/- 1.20 vs. 1.85 +/- 1.16 n fold change; adjusted P< 0.000001).
      DISCUSSION: Data reported here suggest that the UCP2 -866A/55Val/Ins haplotype is
      associated with an increased risk for DKD and with a lower eGFR in T2DM patients.
      Furthermore, this mutated haplotype was associated with decreased UCP2 gene
      expression in human kidneys.

PMID- 26218520
TI  - Site-Directed Mutagenesis of a Hyperthermophilic Endoglucanase Cel12B from
      Thermotoga maritima Based on Rational Design.
AB  - To meet the demand for the application of high activity and thermostable
      cellulases in the production of new-generation bioethanol from nongrain-cellulose
      sources, a hyperthermostable beta-1,4-endoglucase Cel12B from Thermotoga maritima
      was selected for further modification by gene site-directed mutagenesis method in
      the present study, based on homology modeling and rational design. As a result,
      two recombinant enzymes showed significant improvement in enzyme activity by 77%
      and 87%, respectively, higher than the parental enzyme TmCel12B. Furthermore, the
      two mutants could retain 80% and 90.5% of their initial activity after incubation
      at 80 degrees C for 8 h, while only 45% for 5 h to TmCel12B. The Km and Vmax of
      the two recombinant enzymes were 1.97+/-0.05 mM, 4.23+/-0.15 MUmol.mg(-1).min(-1)
      of TmCel12B-E225H-K207G-D37V, and 2.97+/-0.12 mM, 3.15+/-0.21 MUmol.mg(-1).min(
      1) of TmCel12B-E225H-K207G, respectively, when using CMC-Na as the substrate. The
      roles of the mutation sites were also analyzed and evaluated in terms of electron
      density, hydrophobicity of the modeled protein structures. The recombinant
      enzymes may be used in the hydrolysis of cellulose at higher temperature in the
      future. It was concluded that the gene mutagenesis approach of a certain active
      residues may effectively improve the performance of cellulases for the industrial
      applications and contribute to the study the thermostable mechanism of
      thermophilic enzymes.

PMID- 26218521
TI  - Large-Scale Brain Network Coupling Predicts Total Sleep Deprivation Effects on
      Cognitive Capacity.
AB  - Interactions between large-scale brain networks have received most attention in
      the study of cognitive dysfunction of human brain. In this paper, we aimed to
      test the hypothesis that the coupling strength of large-scale brain networks will
      reflect the pressure for sleep and will predict cognitive performance, referred
      to as sleep pressure index (SPI). Fourteen healthy subjects underwent this within
      subject functional magnetic resonance imaging (fMRI) study during rested
      wakefulness (RW) and after 36 h of total sleep deprivation (TSD). Self-reported
      scores of sleepiness were higher for TSD than for RW. A subsequent working memory
      (WM) task showed that WM performance was lower after 36 h of TSD. Moreover, SPI
      was developed based on the coupling strength of salience network (SN) and default
      mode network (DMN). Significant increase of SPI was observed after 36 h of TSD,
      suggesting stronger pressure for sleep. In addition, SPI was significantly
      correlated with both the visual analogue scale score of sleepiness and the WM
      performance. These results showed that alterations in SN-DMN coupling might be
      critical in cognitive alterations that underlie the lapse after TSD. Further
      studies may validate the SPI as a potential clinical biomarker to assess the
      impact of sleep deprivation. 

PMID- 26218522
TI  - On the molecular interaction between albumin and ibuprofen: An AFM and QCM-D
      study.
AB  - The adsorption of proteins on surfaces often results in a change of their
      structural behavior and consequently, a loss of bioactivity. One experimental
      method to study interactions on a molecular level is single molecular force
      spectroscopy that permits to measure forces down to the pico-newton range. In
      this work, the binding force between human serum albumin (HSA), covalently
      immobilized on glutaraldehyde modified gold substrates, and ibuprofen sodium salt
      was studied by means of single molecular force spectroscopy. First of all, a
      protocol was established to functionalize atomic force microscopy (AFM) tips with
      ibuprofen. The immobilization protocol was additionally tested by quartz crystal
      microbalance with dissipation (QCM-D) and contact angle measurements. AFM was
      used to characterize the adsorption of HSA on gold substrates, which lead to a
      packed monolayer of thickness slightly lower than the reported value in solution.
      Finally, single molecule spectroscopy results were used to characterize the
      binding force between albumin and ibuprofen and calculate the distance of the
      transition state (0.6 nm) and the dissociation rate constant (0.055 s(-1)). The
      results might indicate that part of the adsorbed protein still preserves its
      functionality upon adsorption.

PMID- 26218523
TI  - A laser-based technology for fabricating a soda-lime glass based microfluidic
      device for circulating tumour cell capture.
AB  - We developed a laser-based technique for fabricating microfluidic microchips on
      soda-lime glass substrates. The proposed methodology combines a laser direct
      writing, as a manufacturing tool for the fabrication of the microfluidics
      structures, followed by a post-thermal treatment with a CO2 laser. This treatment
      will allow reshaping and improving the morphological (roughness) and optical
      qualities (transparency) of the generated microfluidics structures. The use of
      lasers commonly implemented for material processing makes this technique highly
      competitive when compared with other glass microstructuring approaches. The
      manufactured chips were tested with tumour cells (Hec 1A) after being
      functionalized with an epithelial cell adhesion molecule (EpCAM) antibody
      coating. Cells were successfully arrested on the pillars after being flown
      through the device giving our technology a translational application in the field
      of cancer research. 

PMID- 26218524
TI  - Nanoparticle corona for proteins: mechanisms of interaction between dendrimers
      and proteins.
AB  - Protein absorption at the surface of big nanoparticles and formation of 'protein
      corona' can completely change their biological properties. In contrast, we have
      studied the binding of small nanoparticles - dendrimers - to proteins and the
      formation of their 'nanoparticle corona'. Three different types of interactions
      were observed. (1) If proteins have rigid structure and active site buried deeply
      inside, the 'nanoparticle corona' is unaffected. (2) If proteins have a flexible
      structure and their active site is also buried deeply inside, the 'nanoparticle
      corona' affects protein structure, but not enzymatic activity. (3) The
      'nanoparticle corona' changes both the structure and enzymatic activity of
      flexible proteins that have surface-based active centers. These differences are
      important in understanding interactions taking place at a bio-nanointerface. 

PMID- 26218525
TI  - Stable surface coating of silicone elastomer with phosphorylcholine and
      organosilane copolymer with cross-linking for repelling proteins.
AB  - Poly(dimethylsiloxane) (PDMS)-based polymers are widely used in blood-contacting
      medical devices. However, the hydrophobic property causes adsorption of plasma
      proteins and activates blood clotting. There are several techniques for PDMS
      surface modification. However, the efficacy is limited to short duration due to
      the low glass transition temperature of PDMS. The goal of this study is to
      fabricate a highly stable polymer membrane with blood-compatibility on PDMS.
      Here, we synthesized random copolymer of 2-methacryloyloxyethyl phosphorylcholine
      (MPC), 3-methacryloxypropyl trimethoxysilane (MPTMSi) and 3-(methacryloyloxy)
      propyl-tris(trimethylsilyloxy) silane (MPTSSi). These copolymers are covalently
      and physically immobilized on PDMS surface by silane coupling (cross-linking) and
      hydrophobic interaction. Protein adsorption was significantly reduced on MPC
      copolymer-coated PDMS surface. In particular, copolymer containing 50% MPC unit
      was the most effective and maintained the effect for the longest duration (84
      days). From analyses of X-ray reflectometry (XRR) and X-ray photoelectron
      spectroscopy (XPS), it is determined that the density of the polymer membrane is
      an important factor for the long-term stability. In addition, the coating of PDMS
      with MPC copolymer does not influence on oxygen permeability. 

PMID- 26218527
TI  - Stereotype threat reduces false recognition when older adults are forewarned.
AB  - Exposing older adults to ageing stereotypes can reduce their memory for studied
      information--a phenomenon attributed to stereotype threat--but little is known
      about stereotype effects on false memory. Here, we assessed ageing stereotype
      effects on the Deese-Roediger-McDermott false memory illusion. Older adults
      studied lists of semantically associated words, and then read a passage about age
      related memory decline (threat condition) or an age-neutral passage (control
      condition). They then took a surprise memory test with a warning to avoid false
      recognition of non-studied associates. Relative to the control condition,
      activating stereotype threat reduced the recognition of both studied and non
      studied words, implicating a conservative criterion shift for associated test
      words. These results indicate that stereotype threat can reduce false memory, and
      they help to clarify mixed results from prior ageing research. Consistent with
      the regulatory focus hypothesis, threat motivates older adults to respond more
      conservatively when error-prevention is emphasised at retrieval.

PMID- 26218528
TI  - An Organoytterbium(III) Complex Exhibiting Field-Induced Single-Ion-Magnet
      Behavior.
AB  - We present a new mononuclear half-sandwich complex, [Cp*Yb(DAD)(THF)].C7H8 (1),
      based on a paramagnetic Yb(III) ion coordinated by diamagnetic Cp* and
      enediamido[2,6-Me2C6H3NCH?CHNC6H3Me2-2,6](2-) (DAD) ligands exhibiting field
      induced single-ion-magnet behavior. 

PMID- 26218526
TI  - Bifidobacterium longum CCM 7952 Promotes Epithelial Barrier Function and Prevents
      Acute DSS-Induced Colitis in Strictly Strain-Specific Manner.
AB  - BACKGROUND: Reduced microbial diversity has been associated with inflammatory
      bowel disease (IBD) and probiotic bacteria have been proposed for its prevention
      and/or treatment. Nevertheless, comparative studies of strains of the same
      subspecies for specific health benefits are scarce. Here we compared two
      Bifidobacterium longum ssp. longum strains for their capacity to prevent
      experimental colitis. METHODS: Immunomodulatory properties of nine probiotic
      bifidobacteria were assessed by stimulation of murine splenocytes. The immune
      responses to B. longum ssp. longum CCM 7952 (Bl 7952) and CCDM 372 (Bl 372) were
      further characterized by stimulation of bone marrow-derived dendritic cell,
      HEK293/TLR2 or HEK293/NOD2 cells. A mouse model of dextran sulphate sodium (DSS)
      induced colitis was used to compare their beneficial effects in vivo. RESULTS:
      The nine bifidobacteria exhibited strain-specific abilities to induce cytokine
      production. Bl 372 induced higher levels of both pro- and anti-inflammatory
      cytokines in spleen and dendritic cell cultures compared to Bl 7952. Both strains
      engaged TLR2 and contain ligands for NOD2. In a mouse model of DSS-induced
      colitis, Bl 7952, but not Bl 372, reduced clinical symptoms and preserved
      expression of tight junction proteins. Importantly, Bl 7952 improved intestinal
      barrier function as demonstrated by reduced FITC-dextran levels in serum.
      CONCLUSIONS: We have shown that Bl 7952, but not Bl 372, protected mice from the
      development of experimental colitis. Our data suggest that although some
      immunomodulatory properties might be widespread among the genus Bifidobacterium,
      others may be rare and characteristic only for a specific strain. Therefore,
      careful selection might be crucial in providing beneficial outcome in clinical
      trials with probiotics in IBD.

PMID- 26218529
TI  - Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in
      Multifocal Motor Neuropathy.
AB  - Multifocal motor neuropathy is an immune mediated disease presenting with
      multifocal muscle weakness and conduction block. IgM auto-antibodies against the
      ganglioside GM1 are detectable in about 50% of the patients. Auto-antibodies
      against the paranodal proteins contactin-1 and neurofascin-155 and the nodal
      protein neurofascin-186 have been detected in subgroups of patients with chronic
      inflammatory demyelinating polyneuropathy. Recently, auto-antibodies against
      neurofascin-186 and gliomedin were described in more than 60% of patients with
      multifocal motor neuropathy. In the current study, we aimed to validate this
      finding, using a combination of different assays for auto-antibody detection. In
      addition we intended to detect further auto-antibodies against paranodal
      proteins, specifically contactin-1 and neurofascin-155 in multifocal motor
      neuropathy patients' sera. We analyzed sera of 33 patients with well
      characterized multifocal motor neuropathy for IgM or IgG anti-contactin-1, anti
      neurofascin-155 or -186 antibodies using enzyme-linked immunosorbent assay,
      binding assays with transfected human embryonic kidney 293 cells and murine
      teased fibers. We did not detect any IgM or IgG auto-antibodies against contactin
      1, neurofascin-155 or -186 in any of our multifocal motor neuropathy patients. We
      conclude that auto-antibodies against contactin-1, neurofascin-155 and -186 do
      not play a relevant role in the pathogenesis in this cohort with multifocal motor
      neuropathy. 

PMID- 26218530
TI  - Characterization of the Microenvironment in Positive and Negative Sentinel Lymph
      Nodes from Melanoma Patients.
AB  - Melanomas are aggressive skin tumors characterized by high metastatic potential.
      Our previous results indicate that Natural Killer (NK) cells may control growth
      of melanoma. The main defect of blood NK cells was a decreased expression of
      activating NCR1/NKp46 receptor and a positive correlation of NKp46 expression
      with disease outcome in stage IV melanoma patients was found. In addition, in
      stage III melanoma patients, we identified a new subset of mature NK cells in
      macro-metastatic Lymph nodes (LN). In the present studies, we evaluated the
      numbers of NK cells infiltrating primary cutaneous melanoma and analyzed immune
      cell subsets in a series of sentinel lymph nodes (SLN). First, we show that
      NKp46+ NK cells infiltrate primary cutaneous melanoma. Their numbers were related
      to age of patients and not to Breslow thickness. Then, a series of patients with
      tumor-negative or -positive sentinel lymph nodes matched for Breslow thickness of
      the cutaneous melanoma was constituted. We investigated the distribution of
      macrophages (CD68), endothelial cells, NK cells, granzyme B positive (GrzB+)
      cells and CD8+ T cells in the SLN. Negative SLN (SLN-) were characterized by
      frequent adipose involution and follicular hyperplasia compared to positive SLN
      (SLN+). High densities of macrophages and endothelial cells (CD34), prominent in
      SLN+, infiltrate SLN and may reflect a tumor favorable microenvironment. Few but
      similar numbers of NK and GrzB+ cells were found in SLN- and SLN+: NK cells and
      GrzB+ cells were not correlated. Numerous CD8+ T cells infiltrated SLN with a
      trend for higher numbers in SLN-. Moreover, CD8+ T cells and GrzB+ cells
      correlated in SLN- not in SLN+. We also observed that the numbers of CD8+ T cells
      negatively correlated with endothelial cells in SLN-. The numbers of NK, GrzB+ or
      CD8+ T cells had no significant impact on overall survival. However, we found
      that the 5 year-relapse rate was higher in SLN with higher numbers of NK cells. 

PMID- 26218531
TI  - Heat treatment enhances the antimicrobial activity of (+)-Catechin when combined
      with copper sulphate.
AB  - The aim of the study was to compare the antimicrobial activities of freshly made,
      heat-treated (HT) and 14 day stored (+)-Catechin solutions with (+)-catechin
      flavanol isomers in the presence of copper sulphate. (+)-Catechin activity was
      investigated when combined with different ratios of Cu(2+) ; 100 degrees C heat
      treatment; autoclaving; and 14 day storage against Staphylococcus aureus. Cu(2+) 
      (+)-Catechin complexation, isomer structure-activity relationships, and H2 O2
      generation were also investigated. Freshly made, HT, and 14 day stored flavanols
      showed no activity. While combined Cu(2+) -autoclaved (+)-Catechin and -HT(+)
      Catechin activities were similar, HT(+)-Catechin was more active than either
      freshly made (+)-catechin (generating more H2 O2 ) or (-)-Epicatechin (though it
      generated less H2 O2 ) or 14 day-(+)-Catechin (which had similar activity to
      Cu(2+) controls-although it generated more H2 O2 ). When combined with Cu(2+) ,
      in terms of rates of activity, HT(+)-Catechin was lower than (-)-Epigallocatechin
      gallate and greater than freshly made (+)-Catechin. Freshly made and HT(+)
      Catechin formed acidic complexes with Cu(2+) as indicated by pH and UV-vis
      measurements although pH changes did not account for antimicrobial activity.
      Freshly made and HT(+)-Catechin both formed Cu(2+) complexes. The HT(+)-Catechin
      complex generated more H2 O2 which could explain its higher antimicrobial
      activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Natural products attract
      considerable attention in the search for novel antimicrobials, prebiotics and
      antioxidants. Enhanced biological activity of natural products has been
      demonstrated with chemical and heat treatment. This article extends the few
      publications on heat treatments of plant products and combinations with adjuncts,
      to raise antimicrobial activity against pathogens such as Staphylococcus aureus.
      We demonstrated that heat treatment could increase the activity of (+)-Catechin,
      a weak antimicrobial flavanol found commonly in plants in the presence of copper
      sulphate. Heat treatment of readily available resources merits consideration in
      the development of more potent substances for use in clinical settings and
      agriculture.

PMID- 26218532
TI  - The Flagellar Arginine Kinase in Trypanosoma brucei Is Important for Infection in
      Tsetse Flies.
AB  - African trypanosomes are flagellated parasites that cause sleeping sickness.
      Parasites are transmitted from one mammalian host to another by the bite of a
      tsetse fly. Trypanosoma brucei possesses three different genes for arginine
      kinase (AK) including one (AK3) that encodes a protein localised to the
      flagellum. AK3 is characterised by the presence of a unique amino-terminal
      insertion that specifies flagellar targeting. We show here a phylogenetic
      analysis revealing that flagellar AK arose in two independent duplication events
      in T. brucei and T. congolense, the two species of African trypanosomes that
      infect the tsetse midgut. In T. brucei, AK3 is detected in all stages of parasite
      development in the fly (in the midgut and in the salivary glands) as well as in
      bloodstream cells, but with predominance at insect stages. Genetic knockout leads
      to a slight reduction in motility and impairs parasite infectivity towards tsetse
      flies in single and competition experiments, both phenotypes being reverted upon
      expression of an epitope-tagged version of AK3. We speculate that this flagellar
      arginine kinase is important for T. brucei infection of tsetse, especially in the
      context of mixed infections and that its flagellar targeting relies on a system
      equivalent to that discovered for calflagins, a family of trypanosome flagellum
      calcium binding proteins. 

PMID- 26218533
TI  - Is Non-Contrast CT Adequate for the Evaluation of Hepatic Metastasis in Patients
      Who Cannot Receive Iodinated Contrast Media?
AB  - OBJECTIVE: To evaluate the appropriateness of follow-up with only non-enhanced CT
      (NECT) in patients with gastrointestinal cancer. SUBJECTS AND METHODS: This
      retrospective study included 323 patients with colorectal and gastric cancer who
      underwent two consecutive CT examinations (CT1 and CT2), including non-contrast
      and portal venous phase CT images, with an interval of 1 year. Patients were
      divided into 2 groups: Group A included patients with no hepatic metastasis on
      CT1 and with or without newly developed metastasis on CT2 to evaluate the
      diagnostic performance of NECT for detecting newly developed hepatic metastasis;
      Group B included patients with known hepatic metastasis both on CT1 and CT2 to
      evaluate the accuracy of NECT for the assessment of hepatic metastasis based on
      RECIST criteria (version 1.1). Contrast-enhanced CT (CECT) images were considered
      as reference standards. RESULTS: Group A included 172 patients (M:F = 107:65;
      mean age, 62.6 years). Among them, 57 patients had 95 metastases (mean size, 2.2
      +/- 1.3 cm). Per patient and per lesion sensitivity for diagnosing newly
      developed hepatic metastasis was 56.1-66.7% and 52.6-56.8%, respectively. In
      terms of small metastases (<1.5 cm), per lesion sensitivity was significantly
      decreased to 28.1-34.4% (P < 0.05). Metastasis size measurements were
      significantly smaller on NECT (P < 0.001) compared with reference standards. In
      Group B, the accuracy of response evaluation based on RECIST criteria was 65.6
      72.2%. CONCLUSIONS: NECT showed inadequate diagnostic performances in both
      detecting newly developed hepatic metastasis and evaluating the response of
      hepatic metastasis based on RECIST criteria.

PMID- 26218534
TI  - The Americleft Project: A Comparison of Short- and Longer-Term Secondary Alveolar
      Bone Graft Outcomes in Two Centers Using the Standardized Way to Assess Grafts
      Scale.
AB  - OBJECTIVE: To compare length of follow-up and cleft site dental management on
      bone graft ratings from two centers. DESIGN: Blind retrospective analysis of
      cleft site radiographs and chart reviews for determination of cleft-site lateral
      incisor management. PATIENTS: A total of 78 consecutively grafted patients with
      complete clefts from two major cleft/craniofacial centers (43 from Center 1 and
      35 from Center 2). INTERVENTIONS: Secondary iliac crest alveolar bone grafting,
      at a mean age of 9 years 9 months (Center 1: 9 years 7 months; Center 2: 10 years
      0 month). MAIN OUTCOME MEASURES: The Americleft Standardized Way to Assess Grafts
      scale from 0 (failed graft) to 6 (ideal) was used to rate graft outcome at two
      time points (T1, T2). Average T1 was 11 years 1 month of age, 1 year 3 months
      postgraft. Average T2 was 17 years 11 months of age, 8 years 0 months postgraft.
      Six trained and calibrated raters scored each radiograph twice. Reliability was
      calculated at T1 and T2 using weighted kappa. A paired Wilcoxon signed rank test
      (P < .05) tested T1 and T2 differences for each center. A Kruskal-Wallis test was
      used to determine the significance of differences between centers at T1 and T2.
      Correlation tested whether T1 ratings predicted T2. Linear regression determined
      possible factors that might contribute to graft rating changes over time.
      RESULTS: Reliability was good at T1 and T2 (interrater = .713 and .701,
      respectively; intrarater = .790 and .805, respectively). Center 1 scores were
      significantly better than those from Center 2 at both T1 (5.21 versus 3.29) and
      T2 (5.18 versus 3.44). There was no statistical difference between T1 and T2
      scores for either center; although, there was a greater chance of bone graft
      score improving with completion of canine eruption and substitution for missing
      lateral incisors. CONCLUSIONS: Short-term ratings of graft outcomes identified
      significant differences between centers that persisted over time. Dental cleft
      site management influenced final graft outcome.

PMID- 26218536
TI  - Heart beat detection in multimodal physiological data using a hidden semi-Markov
      model and signal quality indices.
AB  - Accurate heart beat detection in signals acquired from intensive care unit (ICU)
      patients is necessary for establishing both normality and detecting abnormal
      events. Detection is normally performed by analysing the electrocardiogram (ECG)
      signal, and alarms are triggered when parameters derived from this signal exceed
      preset or variable thresholds. However, due to noisy and missing data, these
      alarms are frequently deemed to be false positives, and therefore ignored by
      clinical staff. The fusion of features derived from other signals, such as the
      arterial blood pressure (ABP) or the photoplethysmogram (PPG), has the potential
      to reduce such false alarms. In order to leverage the highly correlated temporal
      nature of the physiological signals, a hidden semi-Markov model (HSMM) approach,
      which uses the intra- and inter-beat depolarization interval, was designed to
      detect heart beats in such data. Features based on the wavelet transform, signal
      gradient and signal quality indices were extracted from the ECG and ABP waveforms
      for use in the HSMM framework. The presented method achieved an overall score of
      89.13% on the hidden/test data set provided by the Physionet/Computing in
      Cardiology Challenge 2014: Robust Detection of Heart Beats in Multimodal Data. 

PMID- 26218535
TI  - A Comprehensive Analysis of Replicating Merkel Cell Polyomavirus Genomes
      Delineates the Viral Transcription Program and Suggests a Role for mcv-miR-M1 in
      Episomal Persistence.
AB  - Merkel cell polyomavirus (MCPyV) is considered the etiological agent of Merkel
      cell carcinoma and persists asymptomatically in the majority of its healthy
      hosts. Largely due to the lack of appropriate model systems, the mechanisms of
      viral replication and MCPyV persistence remain poorly understood. Using a semi
      permissive replication system, we here report a comprehensive analysis of the
      role of the MCPyV-encoded microRNA (miRNA) mcv-miR-M1 during short and long-term
      replication of authentic MCPyV episomes. We demonstrate that cells harboring
      intact episomes express high levels of the viral miRNA, and that expression of
      mcv-miR-M1 limits DNA replication. Furthermore, we present RACE, RNA-seq and ChIP
      seq studies which allow insight in the viral transcription program and mechanisms
      of miRNA expression. While our data suggest that mcv-miR-M1 can be expressed from
      canonical late strand transcripts, we also present evidence for the existence of
      an independent miRNA promoter that is embedded within early strand coding
      sequences. We also report that MCPyV genomes can establish episomal persistence
      in a small number of cells for several months, a time period during which viral
      DNA as well as LT-Ag and viral miRNA expression can be detected via western
      blotting, FISH, qPCR and southern blot analyses. Strikingly, despite enhanced
      replication in short term DNA replication assays, a mutant unable to express the
      viral miRNA was severely limited in its ability to establish long-term
      persistence. Our data suggest that MCPyV may have evolved strategies to enter a
      non- or low level vegetative stage of infection which could aid the virus in
      establishing and maintaining a lifelong persistence. 

PMID- 26218537
TI  - Gravimetric enrichment of high lipid and starch accumulating microalgae.
AB  - This study presents gravimetric enrichment of mixed culture to screen starch and
      lipid producing species separately in a sequencing batch reactor. In the enriched
      starch-producing mixed culture photobioreactor, the starch content at the end of
      steady state batch became 3.42 times the beginning of depletion. Whereas in the
      enriched lipid-producing photobioreactor, the lipid content at the end of steady
      state batch became 3 times the beginning of famine phase. The obtained results
      revealed that the gravimetric enrichment is a suitable screening method for
      specific production of storage compounds in none-sterile large-scaled condition. 

PMID- 26218538
TI  - Bioethanol production from carbohydrate-enriched residual biomass obtained after
      lipid extraction of Chlorella sp. KR-1.
AB  - The residual biomass of Chlorella sp. KR-1 obtained after lipid extraction was
      used for saccharification and bioethanol production. The carbohydrate was
      saccharified using simple enzymatic and chemical methods using Pectinex at pH 5.5
      and 45 degrees C and 0.3N HCl at 121 degrees C for 15min with 76.9% and 98.2%
      yield, respectively, without any pretreatment. The residual biomass contained
      49.7% carbohydrate consisting of 82.4% fermentable sugar and 17.6% non
      fermentable sugar, which is valuable for bioethanol fermentation. Approximately
      98.2% of the total carbohydrate was converted into monosaccharide
      (fermentable+non-fermentable sugar) using dilute acid saccharification. The
      fermentable sugar was subsequently fermented to bioethanol through separate
      hydrolysis and fermentation with a fermentation yield of 79.3%. Overall, 0.4g
      ethanol/g fermentable sugar and 0.16g ethanol/g residual biomass were produced.

PMID- 26218539
TI  - Denitrification accelerates granular sludge formation in sequencing batch
      reactors.
AB  - In this study, the role of denitrification on aerobic granular sludge formation
      in sequencing batch reactors (SBRs) was investigated. Formation of aerobic
      granular sludge was faster in SBRs fed with varying concentrations of nitrate or
      nitrite as compared to control, which received no nitrate or nitrite in the feed.
      The majority of the fed nitrate or nitrite was denitrified in the anoxic static
      fill phase, prior to aerobic reaction phase. Sludge characterization showed
      accumulation of calcium and chemical signature of calcium carbonate in the
      nitrate-fed SBRs. Feeding of sodium nitroprusside, a known nitric oxide (NO)
      donor, enhanced aggregation, production of extracellular polymeric substances and
      formation of aerobic granular sludge. The results support the hypothesis that
      denitrification facilitates cell aggregation and accelerates aerobic sludge
      granulation through NO signaling and CaCO3 formation. Nitrate or other
      intermediates of heterotrophic denitrification, therefore, have a positive effect
      on aerobic granulation in SBRs. 

PMID- 26218540
TI  - Continuous inhibition of 11beta-hydroxysteroid dehydrogenase type I in adipose
      tissue leads to tachyphylaxis in humans and rats but not in mice.
AB  - BACKGROUND AND PURPOSE: 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1),
      a target for Type 2 diabetes mellitus, converts inactive glucocorticoids into
      bioactive forms, increasing tissue concentrations. We have compared the
      pharmacokinetic-pharmacodynamic (PK/PD) relationship of target inhibition after
      acute and repeat administration of inhibitors of 11beta-HSD1 activity in human,
      rat and mouse adipose tissue (AT). EXPERIMENTAL APPROACH: Studies included
      abdominally obese human volunteers, rats and mice. Two specific 11beta-HSD1
      inhibitors (AZD8329 and COMPOUND-20) were administered as single oral doses or
      repeat daily doses for 7-9 days. 11beta-HSD1 activity in AT was measured ex vivo
      by conversion of (3) H-cortisone to (3) H-cortisol. KEY RESULTS: In human and rat
      AT, inhibition of 11beta-HSD1 activity was lost after repeat dosing of AZD8329,
      compared with acute administration. Similarly, in rat AT, there was loss of
      inhibition of 11beta-HSD1 activity after repeat dosing with COMPOUND-20 with
      continuous drug cover, but effects were substantially reduced if a 'drug holiday'
      period was maintained daily. Inhibition of 11beta-HSD1 activity was not lost in
      mouse AT after continuous cover with COMPOUND-20 for 7 days. CONCLUSIONS AND
      IMPLICATIONS: Human and rat AT, but not mouse AT, exhibited tachyphylaxis for
      inhibition of 11beta-HSD1 activity after repeat dosing. Translation of observed
      efficacy in murine disease models to human for 11beta-HSD1 inhibitors may be
      misleading. Investigators of the effects of 11beta-HSD1 inhibitors should confirm
      that desired levels of enzyme inhibition in AT can be maintained over time after
      repeat dosing and not rely on results following a single dose.

PMID- 26218541
TI  - In vitro evaluation of suspoemulsions for in situ-forming polymeric microspheres
      and controlled release of progesterone.
AB  - One possibility to obtain a higher dose of drug in a lower formulation volume can
      be by using of saturated quantity of drug in one of the phases of an emulsion.
      These formulations are called suspoemulsions (S/O/W). When a hydrophobic polymer
      is added to the organic phase of suspoemulsions, these formulations can be used
      to entrap the drug inside microspheres after in situ precipitation of the polymer
      drug-excipients mix. In this work, performance and stability of progesterone
      suspensions in triacetin as organic phase of suspoemulsions were evaluated. These
      formulations were compared with O/W emulsions. Mathematical models were used to
      study in vitro release profiles. The results confirmed that S/O/W systems could
      be an attractive alternative to O/W formulations for the entrapment of
      progesterone inside poly(d,l-lactide-co-glycolide) microspheres. Diffusive-based
      models fit the in vitro release of progesterone from in situ-formed microspheres.
      For longer release periods, a time-dependent diffusion coefficient was
      successfully estimated. 

PMID- 26218542
TI  - Changes in a Starting Pitcher's Performance Characteristics Across the Duration
      of a Major League Baseball Game.
AB  - PURPOSE: With a view to informing in-game decision making as it relates to
      strategy and pitcher health, this study examined changes in pitching-performance
      characteristics across 9 innings of Major League Baseball (MLB) games. METHODS:
      129 starting MLB pitchers met the inclusion criteria for this study. Pitch type,
      speed, ball movement, release location, and strike-zone data-collected using the
      MLB's ball-tracking system, PITCHf/x-were obtained for 1,514,304 pitches thrown
      from 2008 to 2014. RESULTS: Compared with the 1st inning, the proportion of hard
      pitches thrown decreased significantly until the 7th inning, while the
      proportions of breaking and off-speed pitches increased. Significant decreases in
      pitch speed, increases in vertical movement, and decreases in release height
      emerged no later than the 5th inning, and the largest differences in all
      variables were generally recorded between the 1st inning and the late innings (7
      9). Pitchers were most effective during the 2nd inning and significantly worse in
      innings 4 and 6. CONCLUSION: These data revealed that several aspects of a
      starting pitcher's pitching characteristics exhibited changes from baseline as
      early as the 2nd or 3rd inning of an MLB game, but this pattern did not reflect
      the changes in his effectiveness. Therefore, these alterations do not appear to
      provide reasonable justification for relieving a starting pitcher, although
      future work must address their relevance to injury. From an offensive standpoint,
      batters in the MLB should anticipate significantly more hard pitches during the
      early innings but more breaking and off-speed pitches, with decreasing speed, as
      the game progresses.

PMID- 26218543
TI  - Correction: Computational Study of Subdural Cortical Stimulation: Effects of
      Simulating Anisotropic Conductivity on Activation of Cortical Neurons.

PMID- 26218544
TI  - Temporal evolution of the distribution of hepatitis E virus genotypes in
      Southwestern France.
AB  - Southwest France is a highly endemic region for hepatitis E virus (HEV). This
      study examined the circulation of HEV strains between 2003 and 2014 in the Midi
      Pyrenees, and compared these data with those from the rest of France. The
      polyproline region (PPR) of the ORF1 region of the HEV genome was also analyzed.
      HEV genotype was determined by sequencing a 348-nt fragment within the ORF2 gene
      for 333 strains in the Midi-Pyrenees and for 571 strains from the rest of France.
      PPR region was characterized for 56 strains. The frequency of subgenotype 3f
      decreased over time, whereas subgenotype 3c increased in the Midi-Pyrenees.
      Repartition of strains did not differ in the Midi-Pyrenees compared to the rest
      of France. HEV3i and HEV4 have been recently detected throughout France. PPR
      lengths showed that two major groups of HEV3f exist. Our study shows that HEV3
      distribution in the Midi-Pyrenees was similar to the whole of France. Local
      dietary habits could explain the higher seroprevalence in the Midi-Pyrenees
      rather the circulation of a particular variant in this region. 

PMID- 26218548
TI  - Are ineffective defence reactions potential target for induced resistance during
      the compatible wheat-powdery mildew interaction?
AB  - Powdery mildew caused by Blumeria graminis f.sp. tritici, an obligate aerial
      biotrophic fungus, would be one of the most damaging wheat (Triticum aestivum)
      diseases without the extensive use of conventional fungicides. In our study, the
      expression levels of some basal defence-related genes were investigated during a
      compatible interaction in order to evaluate wheat reactions to infection, along
      with the different stages of the infectious process in planta. As fungal conidia
      initiated their germination and developed appressorial germ tube (AGT), early
      defence reactions involved the expression of a lipoxygenase (LOX)- and an oxalate
      oxidase (OXO)-encoding genes, followed by activations of corresponding LOX (EC
      1.13.11.12) and OXO (EC 1.2.3.4) activities, respectively. When penetration of
      AGT took place, up-regulation of chitinases (CHI) and PR1-encoding genes
      expression occurred along with an increase of CHI (EC 3.2.1.14) activity.
      Meanwhile, expression of a phenylalanine ammonia-lyase-encoding gene also took
      place. Up-regulation of a phospholipase C- and lipid transfer proteins-encoding
      genes expression occurred during the latest stages of infection. Neither the phi
      glutathione S-transferase (GST)-encoding gene expression nor the GST (EC
      2.5.1.13) activity was modified upon wheat infection by powdery mildew. Whether
      these defence reactions during such a compatible interaction are markers of
      immunity or susceptibility, and whether they have the ability to contribute to
      protection upon modulation of their timing and their intensity by resistance
      inducers are discussed. 

PMID- 26218549
TI  - Effects of phosphorus application on photosynthetic carbon and nitrogen
      metabolism, water use efficiency and growth of dwarf bamboo (Fargesia rufa)
      subjected to water deficit.
AB  - Dwarf bamboo (Fargesia rufa Yi), one of the staple foods for the endangered giant
      pandas, is highly susceptible to water deficit due to its shallow roots. In the
      face of climate change, maintenance and improvement in its productivity is very
      necessary for the management of the giant pandas' habitats. However, the
      regulatory mechanisms underlying plant responses to water deficit are poorly
      known. To investigate the effects of P application on photosynthetic C and N
      metabolism, water use efficiency (WUE) and growth of dwarf bamboo under water
      deficit, a completely randomized design with two factors of two watering (well
      watered and water-stressed) and two P regimes (with and without P fertilization)
      was arranged. P application hardly changed growth, net CO2 assimilation rate
      (P(n)) and WUE in well-watered plants but significantly increased relative growth
      rate (RGR) and P(n) in water-stressed plants. The effect of P application on RGR
      under water stress was mostly associated with physiological adjustments rather
      than with differences in biomass allocation. P application maintained the balance
      of C metabolism in well-watered plants, but altered the proportion of nitrogenous
      compounds in N metabolism. By contrast, P application remarkably increased
      sucrose-metabolizing enzymes activities with an obvious decrease in sucrose
      content in water-stressed plants, suggesting an accelerated sucrose metabolism.
      Activation of nitrogen-metabolizing enzymes in water-stressed plants was
      attenuated after P application, thus slowing nitrate reduction and ammonium
      assimilation. P application hardly enlarged the phenotypic plasticity of dwarf
      bamboo in response to water in the short term. Generally, these examined traits
      of dwarf bamboo displayed weak or negligible responses to water-P interaction. In
      conclusion, P application could accelerate P(n) and sucrose metabolism and slow N
      metabolism in water-stressed dwarf bamboo, and as a result improved RGR and
      alleviated damage from soil water deficit.

PMID- 26218550
TI  - Effects of water deficit on radicle apex elongation and solute accumulation in
      Zea mays L.
AB  - In this study, we examined the effects of water deficit on the elongation of
      radicles of maize seedlings and on the accumulation of solutes in the radicle
      apices of two maize varieties: VS-22 (tolerant) and AMCCG-2 (susceptible).
      Sections of radicle corresponding to the first 2 mm of the primary roots were
      marked with black ink, and the seedlings were allowed to grow for 24, 48, and 72
      h in polyvinyl chloride (PVC) tubes filled with vermiculite at three different
      water potentials (Psi(w), -0.03, -1.0, and -1.5 MPa). The radicle elongation,
      sugar accumulation, and proline accumulation were determined after each of the
      growth periods specified above. The Psi(w) of the substrate affected the dynamics
      of primary root elongation in both varieties. In particular, the lowest Psi(w) (
      1.5 MPa) inhibited root development by 72% and 90% for the VS-22 and AMCCG-2
      varieties, respectively. The osmotic potential (Psi(o)) was reduced substantially
      in both varieties to maintain root turgor; however, VS-22 had a higher root
      turgor (0.67 MPa) than AMCCG-2 (0.2 MPa). These results suggest that both
      varieties possess a capacity for osmotic adjustment. Sugar began to accumulate
      within the first 24 h of radicle apex growth. The sugar concentration was higher
      in VS-22 root apices compared to AMCCG-2, and the amount of sugar accumulation
      increased with a decrease in Psi(w). Significant amounts of trehalose accumulated
      in VS-22 and AMCCG-2 (29.8 MUmol/g fresh weight [FW] and 5.24 MUmol/g FW,
      respectively). Starch accumulation in the root apices of these two maize
      varieties also differed significantly, with a lower level in VS-22. In both
      varieties, the proline concentration also increased as a consequence of the water
      deficit. At 72 h, the proline concentration in VS-22 (16.2 MUmol/g FW) was almost
      3 times greater than that in AMCCG-2 (5.19 MUmol/g FW). Trehalose also showed a 3
      fold increase in the tolerant variety. Accumulation of these solutes in the root
      growth zone may indicate an osmotic adjustment (OA) to maintain turgor pressure.

PMID- 26218551
TI  - Identification of chondroitin-like molecules from biofilm isolates
      Exiguobacterium indicum A11 and Lysinibacillus sp. C13.
AB  - AIMS: The study aims to investigate whether the bacteria from biofilms can
      produce chondroitin-like molecules (CLMs). METHODS AND RESULTS: Chondroitin
      belongs to the class of glycosaminoglycans. Forty bacteria from biofilms were
      isolated and screened for the production of glycosaminoglycans. Two isolates A11
      and C13 produced 43 and 26 mg l(-1) of chondroitinase AC II degradable
      glycosaminoglycans, respectively, suggesting the possibility of production of
      CLMs by them. These isolates were identified using 16S rDNA sequencing technique
      and fatty acid methyl ester analysis. These were recognized as Exiguobacterium
      indicum A11 (NCIM 5531) and Lysinibacillus sp. C13 (NCIM 5532) respectively.
      These strains were also characterized using polar lipid content and biochemical
      tests. The identity of the glycosaminoglycans produced was further confirmed
      using agarose gel electrophoresis, fourier transform infrared spectroscopy and
      proton nuclear magnetic resonance spectroscopy. CONCLUSIONS: Prokaryotic biofilms
      were found to be a good source of bacteria synthesizing CLMs. Two wild strains
      producing significant amount of the same were identified and characterized.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study exploring natural
      biofilms for the production of the therapeutic molecule,
      chondroitin/glycosaminoglycan. These isolates may be prospective new alternatives
      to recombinant strains that are reported for the production of
      chondroitin/glycoaminoglycan at an industrial scale. The production by these wild
      strains could be commercially attractive if the production is higher and/or can
      be improved further by strain improvement/process engineering. Further, these are
      new additions to the scientific literature on glycosaminoglycan-producing micro
      organisms.

PMID- 26218552
TI  - Effects of imidazolium chloride ionic liquids and their toxicity to Scenedesmus
      obliquus.
AB  - The low volatility of ionic liquids effectively eliminates a major pathway for
      environmental release and contamination; however, the good solubility, low degree
      of environmental degradation and biodegradation of ILs may pose a potential
      threat to the aquatic environment. The growth inhibition of the green alga
      Scenedesmus obliquus by five 1-alkyl-3-methylimidazolium chloride ionic liquids
      (ILs) ([Cnmim]Cl, n=6, 8, 10, 12, 16) was investigated, and the effect on
      cellular membrane permeability and the ultrastructural morphology by ILs
      ([Cnmim]Cl, n=8, 12, 16) were studied. The results showed that the growth
      inhibition rate increased with increasing IL concentration and increasing alkyl
      chain lengths. The relative toxicity was determined to be
      [C6mim]Cl<[C8mim]Cl<[C10mim]Cl<[C12mim]Cl<[C16mim]Cl. The algae were most
      sensitive to imidazolium chloride ILs at 48 h according to the results from the
      growth inhibition rate and cellular membrane permeability tests. The
      ultrastructural morphology showed that the ILs had negative effects on the
      cellular morphology and structure of the algae. The cell wall of treated algae
      became wavy and separated from the cell membrane. Chloroplast grana lamellae
      became obscure and loose, osmiophilic material was deposited in the chloroplast,
      and mitochondria and their cristae swelled. Additionally, electron-dense deposits
      were observed in the vacuoles.

PMID- 26218553
TI  - Ecotoxicological evaluation of swine manure disposal on tropical soils in Brazil.
AB  - Swine production in Brazil results in a great volume of manure that normally is
      disposed of as agricultural fertilizer. However, this form of soil disposal,
      generally on small farms, causes the accumulation of large amounts of manure and
      this results in contaminated soil and water tables. To evaluate the effects of
      increasing concentrations of swine manure on earthworms, several ecotoxicological
      tests were performed using Eisenia andrei as test organism in different tropical
      soils, classified respectively as Ultisol, Oxisol, and Entisol, as well as
      Tropical Artificial Soil (TAS). The survival, reproduction and behavior of the
      earthworms were evaluated in experiments using a completely randomized design,
      with five replications. In the Ultisol, Oxisol and TAS the swine manure showed no
      lethality, but in the Entisol it caused earthworm mortality (LOEC=45 m(3)ha(-1)).
      In the Entisol, the waste reduced the reproductive rate and caused avoidance
      behavior in E. andrei (LOEC=30 m(3)ha(-1)) even in lower concentrations. The
      Entisol is extremely sandy, with low cation exchange capacity (CEC), and this may
      be the reason for the higher toxicity on soil fauna, with the soil not being able
      to hold large amounts of pollutants (e.g. toxic metals), but leaving them in
      bioavailable forms. These results should be a warning of the necessity to
      consider soil parameters (e.g. texture and CEC) when evaluating soil
      contamination by means of ecotoxicological assays, as there still are no
      standards for natural soils in tropical regions. E. andrei earthworms act as
      indicators for a soil to support disposal of swine manure without generating harm
      to agriculture and ecosystems.

PMID- 26218554
TI  - Transfer of microcystin from freshwater lakes to Puget Sound, WA and toxin
      accumulation in marine mussels (Mytilus trossulus).
AB  - Many eutrophic inland freshwater lakes in the Puget Sound Washington region
      produce toxic cyanobacteria blooms annually. While such blooms in lakes tend to
      be viewed as a localized phenomenon, there is significant potential for
      downstream export of toxins to freshwater streams, and marine and brackish water
      environments. However, monitoring for cyanotoxins typically associated with
      freshwaters, such as the hepatotoxin, microcystin (MC) in marine receiving waters
      is rare. In 2013 we studied four eutrophic Puget Sound area lakes to assess both
      toxin transport to marine waters and its potential accumulation in marine
      shellfish, specifically mussels. Shellfish beds are extensive throughout Puget
      Sound, and recreational harvest occurs downstream of our study lakes, so a study
      goal was to also assess if shellfish consumption poses a human health risk for MC
      exposure. We confirm, for the first time, freshwater to marine transfer of MCs in
      Puget Sound with subsequent bioaccumulation of MC by mussels. ELISA analysis
      estimated maximum MC concentrations in source lakes of 2700 MUg/L, up to 0.34
      MUg/L in marine waters and 6.5 MUg/kg in mussels. Confirmatory analyses by LC
      MS/MS on water and mussel samples identified MC-LA as the major toxin. Although
      we found relatively low MC levels in mussels, our study implies that potential
      concern for human food safety is justified and warrants further investigation.

PMID- 26218555
TI  - Self-Pillared, Single-Unit-Cell Sn-MFI Zeolite Nanosheets and Their Use for
      Glucose and Lactose Isomerization.
AB  - Single-unit-cell Sn-MFI, with the detectable Sn uniformly distributed and
      exclusively located at framework sites, is reported for the first time. The
      direct, single-step, synthesis is based on repetitive branching caused by
      rotational intergrowths of single-unit-cell lamellae. The self-pillared, meso-
      and microporous zeolite is an active and selective catalyst for sugar
      isomerization. High yields for the conversion of glucose into fructose and
      lactose to lactulose are demonstrated. 

PMID- 26218556
TI  - Asymmetric Synthesis of alpha-Amino Ketones by Bronsted Acid Catalysis.
AB  - The highly efficient, regioselective, and enantioselective transfer hydrogenation
      of alpha-keto ketimines and reductive amination of diketones by Bronsted acid
      catalysis is described. A series of chiral alpha-amino ketones is prepared in
      high yields (up to >99%), excellent regioselectivities (up to >99:1), and
      enantioselectivities (up to 98% ee). This method has broad substrate scope. 

PMID- 26218557
TI  - Endometrial injury prior to assisted reproductive techniques for recurrent
      implantation failure: a systematic literature review.
AB  - Endometrial injury to improve implantation for women undergoing assisted
      reproductive techniques has attracted a lot of attention recently and has rapidly
      become incorporated into clinical practice. The aim of this study is, thus, to
      assess the effectiveness and safety of endometrial injury performed in the cycle
      preceding assisted reproductive techniques in women with recurrent implantation
      failure. Electronic database searches, including MEDLINE, EMBASE, CENTRAL and
      grey literature, up to 30th May 2015 were conducted with no restrictions.
      Randomized controlled trials comparing endometrial injury versus placebo or no
      treatment in the cycle preceding assisted reproductive techniques in women with
      recurrent implantation failure were selected. The primary outcome was live birth
      rate. Secondary outcomes were clinical pregnancy, implantation, miscarriage and
      procedure-related complication rates. Of the 1115 publications identified, 4 met
      the inclusion criteria. Meta-analysis was not possible due to significant
      clinical heterogeneity among the included studies. Patients' characteristics
      differed, as did the intervention used with endometrial injury being performed at
      different phases of the preceding menstrual cycle. Moreover, the effect of
      endometrial injury on live birth and clinical pregnancy rates were inconsistent
      among the included studies. In summary, there is currently insufficient evidence
      to support the use of endometrial injury in women with recurrent implantation
      failure undergoing assisted reproductive techniques while the procedure
      associated complication rate has not been assessed. Clinical implementation
      should, thus, be deferred until robust evidence becomes available. 

PMID- 26218558
TI  - The presence of lysyl oxidase-like enzymes in human control and keratoconic
      corneas.
AB  - PURPOSE: Lysyl oxidases, a family comprising lysyl oxidase (LOX) and four LOX
      like enzymes (LOXL1-4), catalyse the cross-linking of elastin and collagen
      fibrils. Keratoconus (KC) is characterized by progressive thinning leading to
      irregular astigmatism, resulting in significant visual impairment. Although the
      pathogenesis of KC remains unclear, one of the current hypotheses is based on
      alterations in the organization and structure of collagen fibrils. To extend
      existing general knowledge about cross-linking enzymes in the human cornea, in
      the present study we have focused on the detection of LOXL enzymes. METHOD: The
      localization and distribution of LOXL1-4 were assessed in cryosections of 7
      control donors (three males and three females; 25-68 years; mean age 46+/-17.6
      years) and 8 KC corneas (5 males and 3 females; 25-46 years; mean age 31.3+/-7.5
      years) using indirect fluorescent immunohistochemistry (IHC). The specimens were
      examined using an Olympus BX51 microscope (Olympus Co., Tokyo, Japan) at a
      magnification of 200-1000x. Western blot analysis of 4 control and 4 KC corneas
      was performed for all tested enzymes. RESULTS: All four LOX-like enzymes were
      present in all layers of control corneas as well as in the limbus and
      conjunctiva. Almost no differences between control and pathological specimens
      were found for LOXL1. A lower staining intensity of LOXL2 was found using IHC and
      Western blot analysis in KC specimens. Decreases of the signal and small
      irregularities in the staining were found in the epithelium, keratocytes and
      extracellular matrix, where a gradual anterior-posterior weakening of the signal
      was observed. LOXL3 IHC staining was lower in the corneal stromal extracellular
      matrix and keratocytes of KC samples. No prominent differences were detected
      using IHC for LOXL4, but a slight decrease was observed in KC corneas using
      Western blot analysis. CONCLUSION: We presume that the decrease of LOXL2 in KC
      corneas is more likely a consequence of the associated pathological processes
      (activation of stromal cells due to tissue weakening and consequent structural
      changes) than a direct cause leading to KC development. At this time, we are
      unable to provide a coherent explanation for the observed decrease of LOXL3 and
      LOXL4 in KC corneas.

PMID- 26218559
TI  - Efficiency of a closed-coupled solar pasteurization system in treating roof
      harvested rainwater.
AB  - Many studies have concluded that roof harvested rainwater is susceptible to
      chemical and microbial contamination. The aim of the study was thus to conduct a
      preliminary investigation into the efficiency of a closed-coupled solar
      pasteurization system in reducing the microbiological load in harvested rainwater
      and to determine the change in chemical components after pasteurization. The
      temperature of the pasteurized tank water samples collected ranged from 55 to 57
      degrees C, 64 to 66 degrees C, 72 to 74 degrees C, 78 to 81 degrees C and 90 to
      91 degrees C. Cations analyzed were within drinking water guidelines, with the
      exception of iron [195.59 MUg/L (55 degrees C)-170.1 MUg/L (91 degrees C)],
      aluminum [130.98 MUg/L (78 degrees C)], lead [12.81 MUg/L (55 degrees C)-13.2
      MUg/L (91 degrees C)] and nickel [46.43 MUg/L (55 degrees C)-32.82 MUg/L (78
      degrees C)], which were detected at levels above the respective guidelines in the
      pasteurized tank water samples. Indicator bacteria including, heterotrophic
      bacteria, Escherichia coli and total coliforms were reduced to below the
      detection limit at pasteurization temperatures of 72 degrees C and above.
      However, with the use of molecular techniques Yersinia spp., Legionella spp. and
      Pseudomonas spp. were detected in tank water samples pasteurized at temperatures
      greater than 72 degrees C. The viability of the bacteria detected in this study
      at the higher temperature ranges should thus be assessed before pasteurized
      harvested rainwater is used as a potable water source. In addition, it is
      recommended that the storage tank of the pasteurization system be constructed
      from an alternative material, other than stainless steel, in order for a closed
      coupled pasteurization system to be implemented and produce large quantities of
      potable water from roof harvested rainwater.

PMID- 26218560
TI  - Effects of PCBs and PBDEs on thyroid hormone, lymphocyte proliferation,
      hematology and kidney injury markers in residents of an e-waste dismantling area
      in Zhejiang, China.
AB  - Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are
      two typical categories of contaminants released from e-waste dismantling
      environments. In China, the body burdens of PCBs and PBDEs are associated with
      abnormal thyroid hormones in populations from e-waste dismantling sites, but the
      results are limited and contradictory. In this study, we measured the serum
      levels of PCBs and PBDEs and the thyroid hormone free triiodothyronine (FT3),
      free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in 40 residents in an
      e-waste dismantling area and in 15 residents in a control area. Additionally, we
      also measured some lymphocyte proliferation indexes, hematologic parameters and
      kidney injury markers, including white blood cells, neutrophils, monocytes,
      lymphocytes, hemoglobin, platelets, serum creatinine and beta 2-microglobulin
      (beta2-MG). The results indicated that the mean level of SigmaPCBs in the
      exposure group was significantly higher than that in the control group (964.39
      and 67.98 ng g(-1), p<0.0001), but the mean level of SigmaPBDEs in the exposure
      group was not significantly higher than that in the controls (139.32 vs. 75.74 ng
      g(-1), p>0.05). We determined that serum levels of FT3, FT4, monocytes and
      lymphocytes were significantly lower, whereas the levels of neutrophils,
      hemoglobin, platelets and serum creatinine were significantly higher in the
      exposed group (p<0.05). The mean level of SigmaPCBs was negatively correlated
      with levels of FT3, FT4, monocytes and lymphocytes (p<0.05) and positively
      correlated with levels of neutrophils, hemoglobin, serum creatinine and beta2-MG
      (p<0.05). Additionally, the mean level of SigmaPBDEs was positively correlated
      with levels of white blood cells, hemoglobin and platelets (p<0.05). Our data
      suggest that exposure to an e-waste dismantling environment may increase the body
      burdens of PCBs and the specific PBDEs congeners in native residents and that the
      contaminants released from e-waste may contribute to abnormal changes in body
      levels of thyroid hormone, hematology and kidney injury markers.

PMID- 26218561
TI  - Toxicity in lead salt spiked soils to plants, invertebrates and microbial
      processes: Unraveling effects of acidification, salt stress and ageing reactions.
AB  - The fate and effects of toxic trace metals in soil freshly spiked soluble metal
      salts do not mimic those of metals in the field. This study was set up to test
      the magnitude of effects of salinity, acidification, and ageing on toxicity of
      lead (Pb) to plants, invertebrates and soil microbial processes. Three soils were
      spiked with Pb2+ salts up to a concentration of 8000 mg Pb/kg and were tested
      either after spiking, after soil leaching followed by pH correction, or after a 5
      year outdoor ageing period with free drainage followed by pH correction. Soil
      solution ionic strength exceeded 150 mmol/L in soils tested directly after
      spiking and this decreased partially after leaching and returned back to
      background values after 5-year outdoor equilibration. Chronic toxicity to two
      plants, two invertebrates, and three microbial endpoints was consistently found
      in all spiked soils that were not leached. This toxicity significantly decreased
      or became absent after 5 years of ageing in 19 of the 20 toxicity tests by a
      factor 8 (median factor; range: 1.4->50), measured by the factor increase of
      total soil Pb dose required to induce 10% inhibition. The toxicity of Pb in
      leached soils was intermediate between the other two treatments. The lowest
      detectable chronic thresholds (EC10) in aged soils ranged 350-5300 mg Pb/kg.
      Correlation analysis, including data of Pb2+ speciation in soil solution,
      suggests that reduced ionic strength rather than acidification or true ageing is
      the main factor explaining the soil treatment effects after spiking. It is
      suggested that future toxicity studies should test fine PbO powder as a relevant
      source for Pb in soils to exclude the confounding salt effects.

PMID- 26218562
TI  - Assessing visual green effects of individual urban trees using airborne Lidar
      data.
AB  - Urban trees benefit people's daily life in terms of air quality, local climate,
      recreation and aesthetics. Among these functions, a growing number of studies
      have been conducted to understand the relationship between residents' preference
      towards local environments and visual green effects of urban greenery. However,
      except for on-site photography, there are few quantitative methods to calculate
      green visibility, especially tree green visibility, from viewers' perspectives.
      To fill this research gap, a case study was conducted in the city of Cambridge,
      which has a diversity of tree species, sizes and shapes. Firstly, a photograph
      based survey was conducted to approximate the actual value of visual green
      effects of individual urban trees. In addition, small footprint airborne Lidar
      (Light detection and ranging) data was employed to measure the size and shape of
      individual trees. Next, correlations between visual tree green effects and tree
      structural parameters were examined. Through experiments and gradual refinement,
      a regression model with satisfactory R2 and limited large errors is proposed.
      Considering the diversity of sample trees and the result of cross-validation,
      this model has the potential to be applied to other study sites. This research
      provides urban planners and decision makers with an innovative method to analyse
      and evaluate landscape patterns in terms of tree greenness.

PMID- 26218564
TI  - Size distributions of PM, carbons and PAHs emitted from a generator using blended
      fuels containing water.
AB  - This investigation studied the size distributions of particulate matter (PM),
      particulate carbon, and polycyclic aromatic hydrocarbons (PAHs) that are emitted
      from a generator that is fueled by diesel that is blended with waste-edible-oil
      biodiesel and water-containing acetone. PM samples were collected using a micro
      orifice uniform deposit impactor (MOUDI) and a Nano-MOUDI (with aerodynamic
      diameters of 0.01-18 MUm). The results reveal that waste-edible biodiesel blended
      with water-containing acetone (W5WA3 or W20WA3) at a load of 3 kW emitted lower
      SigmaPM, SigmaPM-EC, SigmaPM-OC, SigmaT-PAHs or SigmaT-BaPeq concentrations than
      did D100, in all 13 particle size ranges, and these reductions of emissions of
      submicron particles exceeded 85%. Furthermore, W20WA3 emitted significantly lower
      concentrations of Total-PAHs and Total-BaPeq in four nano/ultrafine particle size
      ranges. Therefore, water-containing acetone biodieselhols can be utilized as
      alternatives to petroleum diesel as fuel to reduce the dangers to human health
      that are posed by emissions from diesel engines.

PMID- 26218563
TI  - Autism spectrum disorder prevalence and proximity to industrial facilities
      releasing arsenic, lead or mercury.
AB  - Prenatal and perinatal exposures to air pollutants have been shown to adversely
      affect birth outcomes in offspring and may contribute to prevalence of autism
      spectrum disorder (ASD). For this ecologic study, we evaluated the association
      between ASD prevalence, at the census tract level, and proximity of tract
      centroids to the closest industrial facilities releasing arsenic, lead or mercury
      during the 1990s. We used 2000 to 2008 surveillance data from five sites of the
      Autism and Developmental Disabilities Monitoring (ADDM) network and 2000 census
      data to estimate prevalence. Multi-level negative binomial regression models were
      used to test associations between ASD prevalence and proximity to industrial
      facilities in existence from 1991 to 1999 according to the US Environmental
      Protection Agency Toxics Release Inventory (USEPA-TRI). Data for 2489 census
      tracts showed that after adjustment for demographic and socio-economic area-based
      characteristics, ASD prevalence was higher in census tracts located in the
      closest 10th percentile compared of distance to those in the furthest 50th
      percentile (adjusted RR=1.27, 95% CI: (1.00, 1.61), P=0.049). The findings
      observed in this study are suggestive of the association between urban
      residential proximity to industrial facilities emitting air pollutants and higher
      ASD prevalence. 

PMID- 26218565
TI  - Determination of endocrine disrupting compounds and their metabolites in fish
      bile.
AB  - This work describes a new methodology for the simultaneous determination of a
      large variety of emerging and persistent organic compounds and some of their
      metabolites in fish bile samples. The target compounds were musk fragrances,
      alkyl phenols, hormones, pesticides, phthalate esters and bisphenol-A, all of
      them with a known endocrine disrupting effect. To achieve the determination these
      three steps were optimized: i) an enzymatic hydrolysis of the metabolites to
      render the unconjugated compounds; ii) the solid phase extraction of the target
      analytes (Plexa cartridges 200-mg); and, iii) a clean-up of the extracts
      (Florisil cartridges 1-g). The samples were analyzed by gas-chromatography-mass
      spectrometry (GC-MS), though the polar fraction required a previous
      derivatization with O-bis (trimethylsilyl) trifluoroacetamide. Good apparent
      recoveries (63-122%), repeatability (<20%) and limits of detection (LODs) ranging
      between 0.04 and 459 ng/mL were obtained. This method was applied to the analysis
      of the target analytes in bile samples of thicklip grey mullets (Chelon labrosus)
      from five different populations of the Basque Coast (South East Bay of Biscay)
      during the period of May-June 2012. The target analytes were found at
      concentrations ranging from <LOD to 19,226 ng/mL and the most polluted site was
      Gernika. Bioconcentration factors (log BCF) were estimated (range of 1.69-5.55)
      and BBP and NP mix showed the highest values. A deep discussion has been carried
      out in order to explain the different concentration levels of the different
      sampling sites.

PMID- 26218566
TI  - Thallium occurrence and partitioning in soils and sediments affected by mining
      activities in Madrid province (Spain).
AB  - Thallium (Tl) and its compounds are toxic to biota even at low concentrations but
      little is known about Tl concentration and speciation in soils. An understanding
      of the source, mobility, and dispersion of Tl is necessary to evaluate the
      environmental impact of Tl pollution cases. In this paper, we examine the Tl
      source and dispersion in two areas affected by abandoned mine facilities whose
      residues remain dumped on-site affecting to soils and sediments of natural water
      courses near Madrid city (Spain). Total Tl contents and partitioning in soil
      solid phases as determined by means of a sequential extraction procedure were
      also examined in soils along the riverbeds of an ephemeral and a permanent
      streams collecting water runoff and drainage from the mines wastes. Lastly,
      electronic microscopy and cathodoluminescence probe are used as a suitable
      technique for Tl elemental detection on thallium-bearing phases. Tl was found
      mainly bound to quartz and alumino-phyllosilicates in both rocks and examined
      soils. Besides, Tl was also frequently found associated to organic particles and
      diatom frustules in all samples from both mine scenarios. These biogenic
      silicates may regulate the transfer of Tl into the soil-water system. 

PMID- 26218567
TI  - A physiologically based toxicokinetic (PBTK) model for moderately hydrophobic
      organic chemicals in the European eel (Anguilla anguilla).
AB  - The European eel (Anguilla anguilla) is a facultatively catadromous fish species
      with a complex life cycle. Its current population status is alarming: recruitment
      has decreased drastically since the 1980s and its stock is still considered to be
      outside safe biological limits. Although there is no consensus on the reasons for
      this situation, it is currently thought to have resulted from a combination of
      different stressors, including anthropogenic contaminants. To deepen our
      understanding of the processes leading to the accumulation of lipophilic organic
      contaminants in yellow eels (i.e. the feeding, continental growth stage), we
      developed a physiologically based toxicokinetic model using our own data and
      values from the literature. Such models can predict the uptake and distribution
      of water-borne organic chemicals in the whole fish and in different tissues at
      any time during exposure. The predictive power of the model was tested against
      experimental data for six chemicals with n-octanol-water partitioning coefficient
      (log Kow) values ranging from 2.13-4.29. Model performance was excellent, with a
      root mean squared error of 0.28 log units. This model has the potential to help
      identify suitable habitats for restocking under eel management plans. 

PMID- 26218568
TI  - Occurrence and exposure evaluation of perchlorate in indoor dust and diverse food
      from Chengdu, China.
AB  - A total of 688 samples, including 520 food samples belonging to 29 food types in
      10 groups, 63 drinking water, and 105 indoor dust samples were collected during
      May to November in 2014 in Chengdu and Tianjin (only dust samples in Tianjin),
      China to investigate the perchlorate levels in these samples and to estimate the
      related exposure to Chinese people. Significant difference in indoor dust
      perchlorate levels was found between Chengdu and Tianjin, with the concentrations
      ranging from 0.11 to 38.8 mg/kg in Chengdu, and from 0.72 to 119 mg/kg in
      Tianjin. The mean perchlorate levels in 10 groups of food samples were in the
      order of vegetables>wheaten flour~egg, and wheaten flour>milk>sea food>livestock
      meats~poultry~freshwater fish>fruits>steamed rice, while no statistical
      difference in perchlorate levels was found between egg and milk. Exposure
      evaluation indicated that indoor dust contributed little (less than 5%) to the
      total daily perchlorate intake, and food consumption was the primary perchlorate
      exposure route for Chengdu people, followed by drinking water. Based on the
      median perchlorate levels obtained in this study, the daily perchlorate intake
      was below the reference does suggested by the US EPA.

PMID- 26218569
TI  - A U-Shaped Relationship between Body Mass Index and Dysmenorrhea: A Longitudinal
      Study.
AB  - BACKGROUND: Both obesity and dysmenorrhea are prevalent among women. Few
      population-based longitudinal studies investigate the association between body
      mass index (BMI) and dysmenorrhea yielding mixed results, especially for obesity.
      This study aims to investigate the long-term association between BMI and
      dysmenorrhea. METHODS: 9,688 women from a prospective population-based cohort
      study were followed for 13 years. Data were collected through self-reported
      questionnaires. The longitudinal association between dysmenorrhea and BMI or BMI
      change was investigated by logistic regression analysis using generalized
      estimating equations to account for the repeated measures. RESULTS: When the
      women were aged 22 to 27 years, approximately 11% were obese, 7% underweight, and
      25% reported dysmenorrhea. Compared to women with a normal weight, significantly
      higher odds of reporting dysmenorrhea were detected for both women who were
      underweight (odds ratio (OR) 1.34, 95% confidence interval (CI) 1.15, 1.57) and
      obese (OR 1.22, 95% CI 1.11, 1.35). Compared to women who remained at normal
      weight or overweight over time, significant risk was detected for women who:
      remained underweight or obese (OR 1.33, 95% CI 1.20, 1.48), were underweight
      despite weight gain (OR 1.33, 95% CI 1.12, 1.58), became underweight (OR 1.28,
      95% CI 1.02, 1.61). However the higher risk among obese women disappeared when
      they lost weight (OR 1.06, 95% CI 0.85, 1.32). CONCLUSIONS: A U-shaped
      association was revealed between dysmenorrhea and BMI, revealing a higher risk of
      dysmenorrhea for both underweight and obese women. Maintaining a healthy weight
      over time may be important for women to have pain-free periods.

PMID- 26218570
TI  - An Analysis of Organizational Performance Based on Hospital Specialization Level
      and Strategy Type.
AB  - INTRODUCTION: Hospitals are studying the focused factory concept and attempting
      to increase their power in a competitive industry by becoming more specialized.
      METHODOLOGY: This study uses the information theory index (ITI) and the
      Herfindahl-Hirschman index (HHI) to analyze the extent of specialization by
      Korean hospitals that receive national health insurance reimbursements.
      Hierarchical regression analysis is used to assess the impact of hospital
      specialization on the following four aspects of operational performance:
      productivity, profitability, efficiency and quality of care. STUDY RESULTS: The
      results show that a focused strategy (high HHI) improves the income and adjusted
      number of patients per specialist through the efficient utilization of human
      resources. However, a diversified strategy (high ITI) improves the hospital
      utilization ratio, income per bed and adjusted number of patients per bed
      (controlling for material resources such as beds). In addition, as the
      concentration index increases, case-mix mortality rates and referral rates
      decrease, indicating that specialization has a positive relationship with quality
      of care.

PMID- 26218571
TI  - Radiographic morphometry and densitometry predict strength of cadaveric proximal
      humeri more reliably than age and DXA scan density.
AB  - Methods are needed for identifying poorer quality cadaver proximal humeri to
      ensure that they are not disproportionately segregated into experimental groups
      for fracture studies. We hypothesized that measurements made from radiographs of
      cadaveric proximal humeri are stronger predictors of fracture strength than
      chronological age or bone density values derived from dual-energy x-ray
      absorptiometry (DXA) scans. Thirty-three proximal humeri (range: 39-78 years)
      were analyzed for: (1) bone mineral density (BMD, g/cm(2)) using DXA, (2) bulk
      density (g/cm(3)) using DXA and volume displacement, (3) regional bone density in
      millimeters of aluminum (mmAl) using radiographs, and (4) regional mean
      (medial+lateral) cortical thickness and cortical index (CI) using radiographs.
      The bones were then fractured simulating a fall. Strongest correlations with
      ultimate fracture load (UFL) were: mean cortical thickness at two diaphyseal
      locations (r = 0.71; p < 0.001), and mean mmAl in the humeral head (r = 0.70; p <
      0.001). Weaker correlations were found between UFL and DXA-BMD (r = 0.60), bulk
      density (r = 0.43), CI (r = 0.61), and age (r = -0.65) (p values <0.01). Analyses
      between UFL and the product of any two characteristics showed six combinations
      with r-values >0.80, but none included DXA-derived density, CI, or age.
      Radiographic morphometric and densitometric measurements from radiographs are
      therefore stronger predictors of UFL than age, CI, or DXA-derived density
      measurements.

PMID- 26218572
TI  - Sepsis: An update in management.
AB  - Hospitalists are a critical link in providing evidence-based care for patients
      with sepsis across the disease spectrum, from early recognition to recovery. The
      past decade of sepsis research has led to significant findings that will change
      clinical practice for hospital medicine practitioners. Although the incidence of
      severe sepsis in the United States has continued to rise, in-hospital mortality
      has declined. Management of the spectrum of sepsis disorders is no longer
      restricted to the intensive care unit (ICU). This review article will provide an
      update in the management of sepsis for hospitalists based on recently published
      pivotal studies. The expanding evidence base in sepsis includes early goal
      directed therapy/clinical endpoints/sepsis bundles, antibiotics and source
      control, volume resuscitation, ICU considerations (including the use of insulin
      and corticosteroids), mortality/complications, and the newly recognized condition
      of "sepsis survivorship".

PMID- 26218573
TI  - Electrochemically Induced Synthesis of Poly(2,6-carbazole).
AB  - The formation of a poly(2,6-carbazole) derivative during an electrochemical
      polymerization process is shown. Comparison of 3,5-bis(9-octyl-9H-carbazol-2
      yl)pyridine and 3,5-bis(9-octyl-9H-carbazol-3-yl)pyridine by electrochemical and
      UV-Vis-NIR spectroelectrochemical measurements and DFT (density functional
      theory) calculation prove the formation of a poly(2,6-carbazole) derivative. Both
      of the compounds form stable and electroactive conjugated polymers. 

PMID- 26218574
TI  - Ebola Virus Disease: Experience and Decision Making for the First Patients
      outside of Africa.
AB  - David Stephens and colleagues describe their experience of treating patients with
      Ebola virus disease at Emory University in the United States. 

PMID- 26218576
TI  - The Rapid Screening of Triazophos Residues in Agricultural Products by
      Chemiluminescent Enzyme Immunoassay.
AB  - A highly sensitive chemiluminescent enzyme immunoassay (CLEIA) method was
      developed in this study for efficient screening of triazophos residues in a large
      number of samples. Based on the maximum residue limits (MRLs) set by China and
      CAC for triazophos in different agro-products, the representative apple, orange,
      cabbage, zucchini, and rice samples were selected as spiked samples, and the
      triazophos at the concentrations of the MRL values were spiked to blank samples.
      Subsequently, the five samples with the spiked triazophos standard were measured
      by CLEIA 100 times, and the detection results indicated that the correction
      factors of the apple, orange, cabbage, zucchini, and rice were determined as
      0.79, 0.66, 0.85, 0.76, and 0.91, respectively. In this experiment, 1500 real
      samples were detected by both the CLEIA and the GC-MS methods. With the GC-MS
      method, 1462 samples were identified as negative samples and 38 samples as
      positive samples. Based on the correction factors, the false positive rate of the
      CLEIA method was 0.13%, and false negative rate was 0. The results showed that
      the established CLEIA method could be used to screen a large number of real
      samples. 

PMID- 26218575
TI  - An Improved DNA Extraction Method for Efficient and Quantitative Recovery of
      Phytoplankton Diversity in Natural Assemblages.
AB  - Marine phytoplankton are highly diverse with different species possessing
      different cell coverings, posing challenges for thoroughly breaking the cells in
      DNA extraction yet preserving DNA integrity. While quantitative molecular
      techniques have been increasingly used in phytoplankton research, an effective
      and simple method broadly applicable to different lineages and natural
      assemblages is still lacking. In this study, we developed a bead-beating protocol
      based on our previous experience and tested it against 9 species of phytoplankton
      representing different lineages and different cell covering rigidities. We found
      the bead-beating method enhanced the final yield of DNA (highest as 2 folds) in
      comparison with the non-bead-beating method, while also preserving the DNA
      integrity. When our method was applied to a field sample collected at a
      subtropical bay located in Xiamen, China, the resultant ITS clone library
      revealed a highly diverse assemblage of phytoplankton and other micro-eukaryotes,
      including Archaea, Amoebozoa, Chlorophyta, Ciliphora, Bacillariophyta, Dinophyta,
      Fungi, Metazoa, etc. The appearance of thecate dinoflagellates, thin-walled
      phytoplankton and "naked" unicellular organisms indicates that our method could
      obtain the intact DNA of organisms with different cell coverings. All the results
      demonstrate that our method is useful for DNA extraction of phytoplankton and
      environmental surveys of their diversity and abundance. 

PMID- 26218578
TI  - Facility-Related Factors Influencing the Place of Death and Home Care Rates for
      End-Stage Cancer Patients.
AB  - BACKGROUND: In Japan, palliative home care is subject to increasing demand from
      patients. However, the number of deaths at home is still not as high as that of
      palliative home care users. OBJECTIVE: This study aimed to clarify factors
      influencing the place of death and home care rates, involving end-stage cancer
      patients targeted for palliative care by a general home-visit nursing agency.
      METHODS: A total of 87 patients who had used palliative home nursing care
      services provided by the study facility within a 6-year period after its opening
      were studied. RESULTS: The numbers of deaths at home supported by family
      physicians and those in hospital after readmission were 70 and 17, respectively.
      The numbers of deaths at home using services provided by the study facility and
      nurses belonging to it time-dependently increased, revealing a strong correlation
      between them. Furthermore, the place of death and home care rates were closely
      associated with the mean duration of home nursing services and home visits in
      collaboration with family physicians in charge. CONCLUSION: These results suggest
      that it may be possible to increase the rate of home care for end-stage cancer
      patients and meet their desires regarding the place of death through approaches
      to establish trust-based relationships with them and their families, such as
      strengthening manpower in home-visit nursing agencies and promoting collaboration
      between visiting nurses and family physicians in charge during home visits.

PMID- 26218579
TI  - End-of-Life Decisions in Pediatric Cancer Patients.
AB  - BACKGROUND: End-of-life decisions (ELDs) have been investigated in several care
      settings, but rarely in pediatric oncology. OBJECTIVE: The aims of this study
      were to characterize the practice of end-of-life decision making in a Dutch
      academic medical center and to explore pediatric oncologists' perspectives on
      decision making. METHODS: Between 2001 and 2010, in a specified period of 2
      years, 57 children died of cancer. The attending pediatric oncologists of 48
      deceased children were eligible for this study. They were requested to complete a
      retrospective questionnaire on characteristics of ELDs that may have preceded a
      child's death. ELDs were defined as decisions concerning administering or
      forgoing treatment that may unintentionally or intentionally hasten death.
      RESULTS: In 31 of 48 cases (65%) one or more ELDs were made. In 20 of 31 cases
      potentially life-prolonging treatments were discontinued or withheld, and in 22
      of 31 cases drugs were administered to alleviate pain or other symptoms in
      potentially life-shortening dosages. Frequently mentioned considerations for
      making ELDs were no prospects of improvement (n=21;68%) and unbearable suffering
      without a curative perspective (n=13;42%). ELDs were discussed with parents in
      all cases, and with the child in 9 of 31 cases. After the child's death, the
      pediatric oncologist met the parents in all ELD cases and in 11 of 17 non-ELD
      cases. Pediatric oncologists were satisfied with care around the child's death in
      90% of the ELD cases versus 59% of the non-ELD cases. CONCLUSIONS: In two-thirds
      of cases, ELDs preceded the death of a child with cancer. This is the first study
      providing insights into the characteristics of ELDs from a pediatric oncologist's
      point of view.

PMID- 26218581
TI  - Venting Gastrostomy at Home for Symptomatic Management of Bowel Obstruction in
      Advanced/Recurrent Ovarian Malignancy: A Case Series.
AB  - Malignant bowel obstruction (MBO) frequently defines the trajectory of end-stage
      ovarian cancer and results in severe physical and psychological distress in
      patients and their caregivers. Venting gastrostomy (VG) is an alternative to both
      prolonged medical therapy with nasogastric intubation and intestinal
      bypass/diversion for refractory MBO. Limited published data from large academic
      research centers support use of VG in patients with advanced ovarian cancer and
      MBO. In this case series, we describe supportive care outcomes in ovarian cancer
      patients with MBO receiving the effects of VG in a community setting. Six cases
      of advanced ovarian cancer involving MBO were evaluated for VG from July 2009
      through February 2012. Five of six patients were managed with VG. Our experience
      suggests that VG may be beneficial in controlling nausea and vomiting in ovarian
      cancer patients with MBO and that VG placement with concurrent evacuation of
      large-volume ascites was associated with minimal complications. Future
      prospective studies to evaluate the benefits of VG are warranted. 

PMID- 26218580
TI  - Radiation-Refractory Brain Metastases in Patients with Non-Small Cell Lung
      Cancer.
AB  - BACKGROUND: Numerous studies have focused on the treatment of non-small cell lung
      cancer patients with brain metastases. However, to our knowledge, few have sought
      to examine outcomes in patients who required whole brain radiation and developed
      radiation-refractory disease. METHODS: This study examined the medical records of
      all non-small cell lung cancer patients who developed brain metastases between
      2004 and 2013, required whole brain radiation, and received their cancer
      treatment at the Mayo Clinic in Rochester, Minnesota. RESULTS: A total of 141
      patients, most of whom were symptomatic, met the above criteria. Of these, 33
      (23%) did not tolerate a corticosteroid taper and were therefore deemed to have
      radiation-refractory disease. The median survival of patients with and without
      radiation-refractory disease was 3.12 and 4.27 months, respectively, (hazard
      ratio [HR]: 0.65 [95% confidence interval (CI): 0.44-0.99]; p=0.04 by log rank
      test). In a subgroup analysis of patients with radiation-refractory disease
      (n=33) and radio-responsive disease (n=43), median survival was 3.12 and 5.94
      months, respectively (HR: 0.43 [95% CI: 0.26-0.70]). Among patients with
      radiation-refractory disease, 12 received chemotherapy after radiation, and two
      received erlotinib. Systemic therapy was associated with improved symptoms in two
      patients but did not appear to improve survival. CONCLUSION: Non-small cell lung
      cancer patients with radiation-refractory brain metastases represent a small
      subgroup who have a short survival and who appear to derive minimal benefit from
      systemic cancer therapy.

PMID- 26218582
TI  - Bioerosion of Inorganic Hard Substrates in the Ordovician of Estonia (Baltica).
AB  - The earliest bioeroded inorganic hard substrates in the Ordovician of Estonia
      appear in the Dapingian. Hardgrounds are also known from the Sandbian and Katian.
      Most of the bioerosion of inorganic hard substrates occurs as the boring
      Trypanites Magdefrau, 1932 along with some possible Gastrochaenolites borings.
      North American hardground borings are more diverse than those in Baltica. In
      contrast to a worldwide trend of increasing boring intensity, the Estonian record
      seems to show no increase in boring intensities during the Middle and Late
      Ordovician. Hardgrounds seem to be more common during the temperate climate
      interval of the Ordovician calcite sea in Estonia (seven hardgrounds during 15
      my) than in the part with a tropical climate (four hardgrounds during 12 my).
      Bioerosion is mostly associated with carbonate hardgrounds, but cobbles and
      pebbles broken from the hardgrounds are also often penetrated by Trypanites
      borings. The general diversity of boring ichnotaxa in Baltica increased from one
      ichnospecies in the Cambrian to seven by the end of Ordovician, showing the
      effect of the GOBE on bioeroding ichnotaxa. The diversity of inorganic hard
      substrate borers increased by only two times. This difference can be explained by
      the wider environmental distribution of organic as compared to inorganic
      substrates in the Ordovician seas of Baltica, and their more continuous temporal
      availability, which may have caused increased specialization of several borers.
      The inorganic substrates may have been bioreroded only by the generalists among
      boring organisms. 

PMID- 26218583
TI  - Impact of Environmental and Disturbance Variables on Avian Community Structure
      along a Gradient of Urbanization in Jamshedpur, India.
AB  - Gradient pattern analysis was used to investigate the impact of environmental and
      disturbance variables on species richness, species diversity, abundance and
      seasonal variation of birds in and around Jamshedpur, which is one of the fastest
      growing cities of India. It was observed that avian community structure is highly
      influenced by the vegetation habitat variables, food availability and human
      related disturbance variables. A total of 61 species belonging to 33 families
      were recorded from the suburban area. 55 species belonging to 32 families were
      observed in nearby wildland habitat consisting of natural vegetation whereas only
      26 species belonging to 18 families were observed in urban area. Results
      indicated that the suburban habitat had more complex bird community structure in
      terms of higher species richness, higher species diversity and higher evenness in
      comparison to urban and wildland habitat. Bird species richness and diversity
      varied across seasons. Maximum species richness and diversity was observed during
      spring season in all type of habitat. Most of the birds observed in urban areas
      were found to belong to either rare or irregular category on the basis of their
      abundance. The observed pattern of avian community structure is due to combined
      effect of both environmental and human related disturbance variables. 

PMID- 26218585
TI  - Diastereomeric Ellagitannin Isomers from Penthorum chinense.
AB  - From the dried stem of Penthorum chinense (Penthoraceae), 1-O-galloyl-4,6-(R)
      hexahydroxydiphenoyl (HHDP)-beta-D-glucose and 2',4',6'-trihydroxyacetophenone 4'
      O-[4,6-(R)-HHDP]-beta-D-glucoside were isolated together with their (S)-HHDP
      isomers. Ellagitannins with a 4,6-(S)-HHDP-glucose moiety are widely distributed
      in the plant kingdom; however, 4,6-(R)-HHDP glucoses are extremely rare. Lowest
      energy conformers of 1-O-galloyl-(S)- and (R)-HHDP-glucopyranoses were derived by
      density functional theory calculations, and the calculated (1)H and (13)C NMR
      chemical shifts and the (1)H-(1)H coupling constants were in agreement with the
      experimental values. The results revealed a conformational difference of the
      diastereomeric macrocyclic ester rings. In addition, a new compound, 1',3',5'
      trihydroxybenzene 1'-O-[4,6-(S)-HHDP]-beta-D-glucoside, was also isolated.

PMID- 26218584
TI  - Stop Saying That It Is Wrong! Psychophysiological, Cognitive, and Metacognitive
      Markers of Children's Sensitivity to Punishment.
AB  - Neurodevelopmental evidence suggests that children's main decision-making
      strategy is to avoid options likely to induce punishment. However, the cognitive
      and affective factors contributing to children's avoidance to high punishment
      frequency remain unknown. The present study explored psychophysiological,
      cognitive, and metacognitive processes associated with sensitivity to punishment
      frequency. We evaluated 54 participants (between 8 and 15 years old) with a
      modified Iowa Gambling Task for children (IGT-C) which included options with
      varying long-term profit and punishment frequencies. Skin conductance responses
      (SCRs) were recorded during this task. Additionally, we assessed IGT-C
      metacognitive knowledge, fluid intelligence, and executive functions.
      Participants exhibited behavioral avoidance and high anticipatory SCRs to options
      with high frequency of punishment. Moreover, age, IGT-C metacognitive knowledge,
      and inhibitory control were associated with individual differences in sensitivity
      to punishment frequency. Our results suggest that children's preference for
      infrequently punished decisions is partially explained by psychophysiological
      signals as well as task complexity and development of cognitive control. 

PMID- 26218586
TI  - Pooled Post Hoc Analysis of Population Pharmacokinetics of Oxycodone and
      Acetaminophen Following Multiple Oral Doses of Biphasic Immediate
      Release/Extended-Release Oxycodone/Acetaminophen Tablets.
AB  - OBJECTIVE: To examine whether biphasic immediate-release (IR)/extended-release
      (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325-mg tablets have clinically
      relevant variability in population pharmacokinetics (PK). DESIGN: Post hoc
      analysis of 2 phase 1 randomized, open-label, multiple-dose crossover studies.
      SETTING: Single contract research organization clinic. SUBJECTS: Men and women
      aged 18 to 55 years with a body mass index of 19 to 30 kg/m(2) and body weight >=
      59 kg. METHODS: Fasted participants (N = 96) received 2 tablets of IR/ER OC/APAP
      7.5/325 mg (total dose, 15/650 mg) every 12 hours for 4.5 days. Population PK
      analysis was performed using nonlinear mixed effects modeling and evaluated 6
      population variables. RESULTS: The average PK estimates for OC were 75 L/hour for
      clearance (CL/F), 756 L for volume of distribution (V/F), and 0.581 per hour for
      absorption rate constant (Ka ). Body weight was a statistically significant
      source of variability in V/F for OC at steady state. Average estimates for APAP
      were 25 L/hour for CL/F and 119 L for V/F. Sex was identified as a statistically
      significant source of variability in CL/F with predicted values for APAP of 25
      L/hour in men and 21 L/hour in women. Body weight affected variability in V/F,
      with a predicted value of 193 L in men and 174 L in women for a 72-kg participant
      at steady state. CONCLUSIONS: Dose adjustments of < 50% are not clinically
      relevant for IR/ER OC/APAP 7.5/325-mg tablets considering the approved dose of 1
      to 2 tablets every 8 to 12 hours; thus, adjustment may be necessary for large
      deviations from normal body weight but not for sex.

PMID- 26218587
TI  - Comparative effectiveness of angiotensin-converting enzyme inhibitors and
      angiotensin II receptor blockers on major adverse cardiac events in patients with
      newly diagnosed type 2 diabetes: a nationwide study.
AB  - BACKGROUND: Guidelines for hypertension management recommend either angiotensin
      converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs)
      as first-line therapies for diabetes population. No head-to-head trial has been
      conducted to determine the priority of ACEI/ARB use for major adverse cardiac
      events (MACEs) in diabetes mellitus. METHODS: Data on patients with newly
      diagnosed diabetes treated with ACEIs or ARBs were collected from Taiwan's
      National Health Insurance Research Database for the period 2000-2010. A total of
      30,777 ARB users and 21,436 ACEI users were identified. One ARB user was matched
      to one ACEI user by propensity score. Intention-to-treat (ITT) and as-treated
      (AT) models were used. The primary outcomes were myocardial infarction, ischemic
      stroke, and all-cause mortality. The secondary outcomes were hospitalization for
      acute kidney injury and hyperkalemia. FINDINGS: Compared with ACEI users
      (n=21,436), ARB users (n=30,777) showed no significant difference in the outcomes
      of myocardial infarction (hazard ratio [HR]: 0.92; 95% confidence interval [CI]:
      0.80 to 1.07), ischemic stroke (HR: 0.95; 95% CI: 0.87 to 1.04), or all-cause
      mortality (HR: 0.95; 95% CI: 0.89 to 1.01) in the ITT analysis. The risks of
      hospitalization for acute kidney injury and hyperkalemia also did not differ
      between groups. ACEI and ARB use also had similar effects on MACEs and adverse
      effects in the AT analysis. CONCLUSIONS: This large cohort study supports the
      comparative effectiveness of ACEIs and ARBs in terms of MACE outcomes in patients
      with incident diabetes.

PMID- 26218588
TI  - Cardiovascular ultrasound exploration contributes to predict incident atrial
      fibrillation in arterial hypertension: the Campania Salute Network.
AB  - BACKGROUND: Interaction of cardiovascular (CV) risk factors with structural and
      hemodynamic alterations as combined promoters of atrial fibrillation (AF) is not
      yet well studied. We designed an observational, longitudinal, retrospective study
      to predict risk of incident AF by combination of CV risk profile, target organ
      damage and therapy in hypertensive patients. METHODS AND RESULTS: We studied 7062
      hypertensive patients without history of AF or prevalent CV disease, with
      ejection fraction (EF) of >=50%, and no more than stage III chronic kidney
      disease. The patients were selected from an open registry, the Campania-Salute
      Network, collecting information from general practitioners and community
      hospitals, in the Campania Region, Southern Italy, networked with the
      Hypertension Center of Federico II University Hospital in Naples. The end-point
      of the present analysis was the detection of first episode of AF by ECG or
      hospital admission, at any point throughout follow-up (median 36months [IQR=10
      74]). During follow-up, AF developed in 117 patients. Baseline older age, greater
      left atrial diameter (LAd), left ventricular mass (LVM), and intimal medial
      thickness (IMT) were independent predictors of AF (all p<0.0001), with no effect
      of CV risk factors. Beta-blockers and diuretics increased risk of incident AF;
      use of medications inhibiting renin-angiotensin system (RAS) reduced risk by 50%
      (all p<0.002). CONCLUSIONS: Older age, increased LAd, and markers of target organ
      damage (increased LVM and IMT), identify the hypertensive phenotype at highest
      risk for AF. CV risk factors do not exhibit significant, independent association.
      Patients on anti-RAS therapy are exposed to lower risk of incident AF.

PMID- 26218590
TI  - Using X-ray computed tomography for quantification of cell proliferation within a
      perfusion bioreactor.

PMID- 26218589
TI  - Early detection of an epidemic erythromelalgia outbreak using Baidu search data.
AB  - Dozens of epidemic erythromelalgia (EM) outbreaks have been reported in China
      since the mid-twentieth century, and the most recent happened in Foshan City,
      Guangdong Province early 2014. This study compared the daily case counts of this
      recent epidemic EM outbreak from February 11 to March 3 with Baidu search data
      for the same period. After keyword selection, filtering and composition, the most
      correlated lag of the EM Search Index was used for comparison and linear
      regression model development. This study also explored the spatial distribution
      of epidemic EM in China during this period based on EM Search Index. The EM
      Search Index at lag 2 was most significantly associated with daily case counts in
      Foshan (rho = 0.863, P < 0.001). It captured an upward trend in the outbreak
      about one week ahead of official report and the linear regression analysis
      indicated that every 1.071 increase in the EM Search Index reflected a rise of 1
      EM cases 2 days earlier. The spatial analysis found that the number of EM Search
      Indexes increased in the middle of Guangdong Province and South China during the
      outbreak period. The EM Search Index may be a good early indicator of an epidemic
      EM outbreak. 

PMID- 26218591
TI  - How Hydrophilic Proteins Form Nonspecific Complexes.
AB  - In the crowded environment of cells, proteins frequently encounter other proteins
      in many possible orientations. Most of these encounters are short-lived because
      the physicochemical properties of the two binding patches do not match. However,
      even for protein pairs that bind tightly, it is not an easy task to find the
      correct binding site on the partner protein and align with it. So far not well
      understood is the source of interaction specificity that favors a small set of
      specific "native" interactions over the multitude of alternative orientations. We
      used molecular dynamics simulations to study nonspecific complexes formed by
      barnase and barstar, cytochrome c and cytochrome c peroxidase, and the complex of
      the N-terminal domain of enzyme I with the histidine-containing phosphocarrier.
      We found that spontaneously forming nonspecific encounters involve interaction
      interfaces smaller than those of the specific complexes and are attracted by
      shorter-range direct interactions between the proteins. 

PMID- 26218592
TI  - RANKL and OPG Polymorphisms Are Associated with Aromatase Inhibitor-Related
      Musculoskeletal Adverse Events in Chinese Han Breast Cancer Patients.
AB  - BACKGROUND: Breast cancer patients treated with aromatase inhibitors (AIs) may
      experience musculoskeletal adverse events (MS-AEs). Several studies have
      confirmed that the RANKL/RANK/OPG signaling pathway plays a dominant role in bone
      health. Therefore, this study aimed to analyze the relationship between the serum
      levels of RANKL, OPG and their SNPs (single nucleotide polymorphisms) with AI
      related MS-AEs. METHODOLOGY AND PRINCIPAL FINDINGS: Patients with early stage,
      hormone-sensitive breast cancer who were receiving AI therapy were enrolled. We
      included 208 cases with AI-related MS-AEs and 212 without (controls). The levels
      of estradiol, bone-turnover markers, multiple inflammatory cytokines, RANKL,OPG
      and lumbar spine BMD were measured, and questionnaires were completed. We
      analyzed 29 SNPs of RANKL, RANK and OPG using Sequenom MassARRAY assays and PCR
      based TaqMan assays. The levels of bone-turnover markers and RANKL and the ratio
      of RANKL/OPG were higher in patients with AI-related MS-AEs than controls (all p
      < 0.05). A genetic assay showed that the RANKL SNP rs7984870 and OPG SNP
      rs2073618 were associated with AI-related MS-AEs. In patients with AI-related MS
      AEs, rs7984870 CC and rs2073618 CC were risk genotypes. Carriers of the rs7984870
      CC genotype were more likely to have a higher RANKL level and RANKL/OPG ratio
      than carriers of the GG genotype, and carriers of the rs2073618 CC genotype were
      more likely to have a lower OPG level and a higher RANKL/OPG ratio than carriers
      of the GG genotype (all p < 0.05). Moreover, risk genotypes were associated with
      higher levels of serum CTX and PINP and a lower lumbar spine BMD (all p < 0.05).
      CONCLUSIONS AND SIGNIFICANCE: In conclusion, the RANKL and OPG risk genotypes
      synergize to negatively impact bone health and predispose breast cancer patients
      to AI-related MS-AEs.

PMID- 26218593
TI  - Mineral Acquisition from Clay by Budongo Forest Chimpanzees.
AB  - Chimpanzees of the Sonso community, Budongo Forest, Uganda were observed eating
      clay and drinking clay-water from waterholes. We show that clay, clay-rich water,
      and clay obtained with leaf sponges, provide a range of minerals in different
      concentrations. The presence of aluminium in the clay consumed indicates that it
      takes the form of kaolinite. We discuss the contribution of clay geophagy to the
      mineral intake of the Sonso chimpanzees and show that clay eaten using leaf
      sponges is particularly rich in minerals. We show that termite mound soil, also
      regularly consumed, is rich in minerals. We discuss the frequency of clay and
      termite soil geophagy in the context of the disappearance from Budongo Forest of
      a formerly rich source of minerals, the decaying pith of Raphia farinifera palms.

PMID- 26218595
TI  - Correction: Codon Optimization, Expression in Escherichia coli, and
      Immunogenicity of Recombinant Chinese Sacbrood Virus (CSBV) Structural Proteins
      VP1, VP2, and VP3.

PMID- 26218596
TI  - Empirical formula on (n,(3)He) reaction cross sections at 14.6MeV neutrons.
AB  - The systematic behavior of the cross sections of (n,(3)He) nuclear reactions has
      been studied by various researches at neutron energy of 14.6MeV. A new empirical
      formula based on the Q-value dependence of the cross sections of the investigated
      reaction has been proposed. The cross sections obtained from the new formula are
      compared with the other proposed formulae results and the experimental data. It
      seems that the present formula based on the Q-value dependence provides the good
      description for cross sections of neutron-induced (n,(3)He) nuclear reactions at
      14.6MeV. 

PMID- 26218594
TI  - Age-Adjusted PSA Levels in Prostate Cancer Prediction: Updated Results of the
      Tyrol Prostate Cancer Early Detection Program.
AB  - OBJECTIVE: To reduce the number of unnecessary biopsies in patients with benign
      prostatic disease, however, without missing significant PCa the present study re
      evaluates the age-dependent PSA cut-offs in the Tyrol Prostate Cancer (PCa) early
      detection program. PATIENTS AND METHODS: The study population included 2225
      patients who underwent prostate biopsy due to elevated PSA levels at our
      department. We divided our patient collective into four age groups: <=49 years (n
      = 178), 50-59 years (n = 597), 60-69 years (n = 962) and >=70 years (n = 488). We
      simulated different scenarios for PSA cut-off values between 1.25 and 6 ng/mL and
      fPSA% between 15 and 21% for all four age groups and calculated sensitivity,
      specificity, confidence intervals and predictive values. RESULTS: PCa was
      detected in 1218 men (54.7%). We found that in combination with free PSA <=21%
      the following PSA cut-offs had the best cancer specificity: 1.75 ng/ml for men
      <=49 years and 50-59 years, 2.25 ng/ml for men aged 60-69 years and 3.25 ng/ml
      for men >=70 years. Using these adjusted PSA cut-off values all significant
      tumors are recognized in all age groups, yet the number of biopsies is reduced.
      Overall, one biopsy is avoided in 13 to 14 men (number needed to screen = 13.3,
      reduction of biopsies = 7.5%) when decision regarding biopsy is done according to
      the "new" cut-off values instead of the "old" ones. For the different age groups
      the number needed to screen to avoid one biopsy varied between 9.2 (<=49 years)
      and 17.4 (50-59 years). CONCLUSION: With "new", fine-tuned PSA cut-offs we detect
      all relevant PCa with a significant reduction of biopsies compared to the "old"
      cut-off values. Optimization of age-specific PSA cut-offs is one step towards a
      smarter strategy in the Tyrol PCa Early Detection Program.

PMID- 26218597
TI  - Endovascular treatment of pulmonary arteriovenous malformations in hereditary
      haemorrhagic telangiectasia.
AB  - PRINCIPLES: To assess the efficiency and complication rates of vaso-occlusion of
      pulmonary arteriovenous malformations (PAVMs) in Rendu-Osler-Weber disease
      (hereditary haemorrhagic telangectasia; HHT). METHODS: Seventy-two patients were
      investigated in our institution for HHT between March 2000 and November 2011.
      Sixteen presented PAVMs (22.2%), and 11 (68.8%) were treated with vaso-occlusion
      for a total of 18 procedures. Procedures included coils, plugs and combined
      approaches. Immediate success and recurrence rate, complication were recorded, as
      well as persistent and new PAVMs during clinical and computed tomography (CT)
      follow-up. RESULTS: Eighteen procedures were performed and a total of 37 PAVMs
      were treated, 19 with coils, 16 with plugs and 2 with combined treatment. Mean CT
      follow-up time was 41 months (1-164). No major complication was observed. One
      distal translocation was treated during the same intervention. Two PAVMs
      persisted after treatment (5.7%), both treated by means of plug embolisation. One
      new PAVM was observed during follow-up CT. PAVMs with an afferent artery of less
      than 3mm or asymptomatic PAVMs were not treated. CONCLUSION: Recent studies have
      demonstrated that vaso-occlusion has become the gold standard treatment for PAVM.
      This study is in accordance with previous results and shows a minimal
      complication rate and little recurrence, whether by coils, plugs, or combined
      treatments.

PMID- 26218598
TI  - Cardiovascular Risk Factors Associated with Smaller Brain Volumes in Regions
      Identified as Early Predictors of Cognitive Decline.
AB  - PURPOSE: To determine in a large multiethnic cohort the cardiovascular and
      genetic risk factors associated with smaller volume in the hippocampus,
      precuneus, and posterior cingulate, and their association with preclinical
      deficits in cognitive performance in patients younger and older than 50 years.
      MATERIALS AND METHODS: The institutional review board approved the study and all
      participants provided written informed consent. Eligible for this study were 1629
      participants (700 men and 929 women; mean age, 50.0 years +/- 10.2 [standard
      deviation]) drawn from the population-based Dallas Heart Study who underwent
      laboratory and clinical analysis in an initial baseline visit and approximately 7
      years later underwent brain magnetic resonance imaging with automated volumetry
      and cognitive assessment with the Montreal Cognitive Assessment (MoCA).
      Regression analysis showed associations between risk factors and segmental
      volumes, and associations between these volumes with cognitive performance in
      participants younger and older than 50 years. RESULTS: Lower hippocampal volume
      was associated with previous alcohol consumption (standardized estimate, -0.04; P
      = .039) and smoking (standardized estimate, -0.04; P = .048). Several risk
      factors correlated with lower total brain, posterior cingulate, and precuneus
      volumes. Higher total (standardized estimate, 0.06; P = .050), high-density
      lipoprotein (standardized estimate, 0.07; P = .003), and low-density lipoprotein
      (standardized estimate, 0.04; P = .037) cholesterol levels were associated with
      larger posterior cingulate volume, and higher triglyceride levels (standardized
      estimate, 0.06; P = .004) were associated with larger precuneus volume. Total
      MoCA score was associated with posterior cingulate volume (standardized estimate,
      0.13; P = .001) in younger individuals and with hippocampal (standardized
      estimate, 0.06; P < .05) and precuneus (standardized estimate, 0.08; P < .023)
      volumes in older adults. CONCLUSION: Smaller volumes in specific brain regions
      considered to be early markers of dementia risk were associated with specific
      cardiovascular disease risk factors and cognitive deficits in a predominantly
      midlife multiethnic population-based sample. Additionally, the risk factors most
      associated with these brain volumes differed in participants younger and older
      than 50 years, as did the association between brain volume and MoCA score.

PMID- 26218600
TI  - A comparison of muscle activity in using touchscreen smartphone among young
      people with and without chronic neck-shoulder pain.
AB  - This study aimed to examine differences in muscle activity between young people
      with and without neck-shoulder pain (n = 20 in each group), when they performed
      texting on a smartphone. Texting was compared between using both hands
      ('bilateral texting') and with only one hand ('unilateral texting'). Texting
      tasks were also compared with computer typing. Surface electromyography from
      three proximal postural muscles and four distal hand/thumb muscles on the right
      side was recorded. Compared with healthy controls, young people with neck
      shoulder pain showed altered motor control consisting of higher muscle activity
      in the cervical erector spinae and upper trapezius when performing texting and
      typing tasks. Generally, unilateral texting was associated with higher muscle
      loading compared with bilateral texting especially in the forearm muscles.
      Compared with computer typing, smartphone texting was associated with higher
      activity in neck extensor and thumb muscles but lower activity in upper and lower
      trapezius as well as wrist extensors. PRACTITIONER SUMMARY: This study
      demonstrated that symptomatic individuals had increased muscle activity in the
      neck-shoulder region when texting on a smartphone. Contemporary ergonomic
      guidelines should include advice on how to interact with handheld electronic
      devices to achieve a relaxed posture and reduced muscle load in order to reduce
      the risk of musculoskeletal disorders.

PMID- 26218599
TI  - Persisting high prevalence of pneumococcal carriage among HIV-infected adults
      receiving antiretroviral therapy in Malawi: a cohort study.
AB  - OBJECTIVE: HIV-infected adults have high rates of pneumococcal carriage and
      invasive disease. We investigated the effect of antiretroviral therapy (ART) on
      pneumococcal carriage in HIV-infected adults prior to infant pneumococcal
      conjugate vaccine (PCV) rollout. DESIGN: Observational cohort study. METHODS: We
      recruited HIV-infected adults newly attending a rural HIV clinic in northern
      Malawi between 2008 and 2010. Nasopharyngeal samples were taken at baseline and
      after 6, 12, 18 and 24 months. We compared pneumococcal carriage by ART status
      using generalized estimated equation models adjusted for CD4 cell count, sex,
      seasonality, and other potential confounders. RESULTS: In total, 336 individuals
      were included, of which 223 individuals started ART during follow-up. Individuals
      receiving ART had higher pneumococcal carriage than individuals not receiving ART
      (25.9 vs. 19.8%, P = 0.03) particularly for serotypes not included in PCV13 (16.1
      vs. 9.6% P = 0.003). Following adjustment, increased carriage of non-PCV13
      serotypes was still observed for individuals on ART, but results for all
      serotypes were nonsignificant [all serotypes: adjusted risk ratio (aRR) 1.22
      (0.95-1.56); non-PCV13 serotypes: aRR 1.72, 95% CI 1.13-2.62]. CONCLUSION:
      Pneumococcal carriage in HIV-infected adults in Malawi remained high despite use
      of ART, consistent with failure of mucosal immune reconstitution in the upper
      respiratory tract. There was evidence of increased carriage of non-PCV13
      serotypes. HIV-infected adults on ART could remain an important reservoir for
      pneumococcal diversity post infant pneumococcal vaccine introduction. Control of
      pneumococcal disease in African HIV remains a priority.

PMID- 26218601
TI  - The stability of alcohol consumption between age 16 and 26: Evidence from a
      National Birth Cohort Study.
AB  - This study examined the association between moderate drinking at age 16
      (adolescence) and alcohol consumption at age 26 (young adulthood), whilst
      controlling for possible confounding effects at the individual and family level
      (assessed at birth and age 10). Using the British Cohort Study (BCS70), 6515
      respondents provided data on their adolescent alcohol consumption and other
      behaviours. Of these, 4392 also completed the survey at age 26. Consumption
      patterns established in adolescence persisted, to a large degree, into early
      adulthood. Those adolescents who drank moderately in adolescence drank
      significantly less in adulthood than those adolescents who drank to heavy or
      hazardous levels. Implications for health promotion strategies and guidance are
      discussed. 

PMID- 26218602
TI  - Association of Anxiety Symptoms in Offspring of Bipolar Parents with Serotonin
      Transporter-Linked Polymorphic Region (5-HTTLPR) Genotype.
AB  - OBJECTIVE: Offspring of parents with bipolar disorder (BD) have been shown to be
      at high risk for BD. Anxiety symptoms, even at subclinical levels, have been
      associated with increased risk for BD in these youth. The s-allele of the
      serotonin transporter-linked polymorphic region (5-HTTLPR) has been implicated in
      the pathophysiology of both BD and anxiety disorders and has been associated with
      pharmacological treatment response and increased risk for antidepressant side
      effects. Therefore, we aimed to explore 1) whether anxiety symptoms in offspring
      of BD parents were associated with presence of the 5-HTTLPR s-allele and 2)
      whether anxiety symptoms in the offspring of BD parents according to the 5-HTTLPR
      genotypes are related to antianxiety medication status. METHODS: A total of 64
      offspring of BD parents (mean age: 13.7 years) and 51 healthy controls (HC) (mean
      age: 13.7 years) were compared genetically and on the Multidimensional Anxiety
      Scale for Children (MASC). RESULTS: Offspring of BD parents showed higher levels
      of overall anxiety than did the HC group. Only antianxiety medication naive
      offspring of BD parents were found to have an association between 5-HTTLPR
      genotypes and anxiety symptoms. The antianxiety medication naive offspring of BD
      parents with the s-allele showed higher level of overall anxiety than offspring
      of BD parents with the l/l genotype. No significant differences in anxiety
      symptoms or their association with the 5-HTTLPR genotype were found in the HC
      group. CONCLUSIONS: This study indicated that there may be an association between
      5-HTTLPR genotypes and anxiety symptoms in offspring of BD parents, and that
      antianxiety medication status may affect anxiety symptoms in the offspring of BD
      patients according to genotype.

PMID- 26218603
TI  - Betahistine co-treatment ameliorates dyslipidemia induced by chronic olanzapine
      treatment in rats through modulation of hepatic AMPKalpha-SREBP-1 and PPARalpha
      dependent pathways.
AB  - Second-generation antipsychotics including olanzapine are associated with weight
      gain, dyslipidemia and other metabolic disorders. Both animal and clinical
      studies have shown that co-treatment with betahistine (a histamine H1 receptor
      agonist/H3 receptor antagonist) is effective in controlling olanzapine-induced
      weight gain. In the present study, we investigate whether co-treatment with
      betahistine is able to prevent dyslipidemia induced by chronic olanzapine
      treatment and the underlying mechanisms. Female rats were orally administered
      with olanzapine (1 mg/kg, t.i.d.) for 3.5 consecutive weeks and then a 2.5-week
      drug withdrawal. Then, rats were divided into 4 groups for 5 weeks treatment: (1)
      vehicle, (2) olanzapine-only (1 mg/kg, t.i.d.), (3) betahistine-only (9.6 mg/kg,
      t.i.d.), and (4) olanzapine and betahistine (O+B) co-treatment. After completing
      treatment, hepatic mRNA expression was measured by qRT-PCR, while the protein
      levels were detected by western blot. In our study, olanzapine-only treatment
      significantly increased triglyceride accumulation and non-esterified fatty acids
      (NEFA), and upregulated mRNA expression of sterol regulatory element binding
      protein 1 (SREBP-1) and its target genes, while these alterations were
      ameliorated by O+B co-treatment. Hepatic AMP-activated protein kinase alpha
      (AMPKalpha) was activated in the O+B co-treatment group, with a significant
      reduction in nuclear SREBP-1 protein expression but an increased expression of
      peroxisome proliferator-activated receptor-alpha (PPARalpha) and its-responsive
      molecule(CPT1A), compared with olanzapine-only treatment. In addition, olanzapine
      significantly increased hepatic histamine H1 receptors, while O+B co-treatment
      significantly reversed them to normal levels. This study provided the first
      evidence that betahistine could act on hepatic H1 receptors via modulation of
      AMPKalpha-SREBP-1 and PPARalpha-dependent pathways to ameliorate olanzapine
      induced dyslipidemia in rats.

PMID- 26218604
TI  - Metabolic syndrome and obesity among users of second generation antipsychotics: A
      global challenge for modern psychopharmacology.
AB  - Second generation antipsychotics (SGAs), such as clozapine, olanzapine,
      risperidone and quetiapine, are among the most effective therapies to stabilize
      symptoms schizophrenia (SZ) spectrum disorders. In fact, clozapine, olanzapine
      and risperidone have improved the quality of life of billions SZ patients
      worldwide. Based on the broad spectrum of efficacy and low risk of extrapyramidal
      symptoms displayed by SGAs, some regulatory agencies approved the use of SGAs in
      non-schizophrenic adults, children and adolescents suffering from a range of
      neuropsychiatric disorders. However, increasing number of reports have shown that
      SGAs are strongly associated with accelerated weight gain, insulin resistance,
      diabetes, dyslipidemia, and increased cardiovascular risk. These metabolic
      alterations can develop in as short as six months after the initiation of
      pharmacotherapy, which is now a controversial fact in public disclosure. Although
      the percentage of schizophrenic patients, the main target group of SGAs, is
      estimated in only 1% of the population, during the past ten years there was an
      exponential increase in the number of SGAs users, including millions of non-SZ
      patients. The scientific bases of SGAs metabolic side effects are not yet
      elucidated, but the evidence shows that the activation of transcriptional factor
      SRBP1c, the D1/D2 dopamine, GABA2 and 5HT neurotransmitions are implicated in the
      SGAs cardiovascular toxicity. Polypharmacological interventions are either non-
      or modestly effective in maintaining low cardiovascular risk in SGAs users. In
      this review we critically discuss the clinical and molecular evidence on
      metabolic alterations induced by SGAs, the evidence on the efficacy of classical
      antidiabetic drugs and the emerging concept of antidiabetic polyphenols as
      potential coadjutants in SGA-induced metabolic disorders. 

PMID- 26218607
TI  - Re: Quantification of historical livestock importation into New Zealand 1860
      1979.

PMID- 26218605
TI  - Identification of Caspase Cleavage Sites in KSHV Latency-Associated Nuclear
      Antigen and Their Effects on Caspase-Related Host Defense Responses.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus
      8, is the causative agent of three hyperproliferative disorders: Kaposi's
      sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease.
      During viral latency a small subset of viral genes are produced, including KSHV
      latency-associated nuclear antigen (LANA), which help the virus thwart cellular
      defense responses. We found that exposure of KSHV-infected cells to oxidative
      stress, or other inducers of apoptosis and caspase activation, led to processing
      of LANA and that this processing could be inhibited with the pan-caspase
      inhibitor Z-VAD-FMK. Using sequence, peptide, and mutational analysis, two
      caspase cleavage sites within LANA were identified: a site for caspase-3 type
      caspases at the N-terminus and a site for caspase-1 and-3 type caspases at the C
      terminus. Using LANA expression plasmids, we demonstrated that mutation of these
      cleavage sites prevents caspase-1 and caspase-3 processing of LANA. This
      indicates that these are the principal sites that are susceptible to caspase
      cleavage. Using peptides spanning the identified LANA cleavage sites, we show
      that caspase activity can be inhibited in vitro and that a cell-permeable peptide
      spanning the C-terminal cleavage site could inhibit cleavage of poly (ADP-ribose)
      polymerase and increase viability in cells undergoing etoposide-induced
      apoptosis. The C-terminal peptide of LANA also inhibited interleukin-1 beta (IL
      1beta) production from lipopolysaccharide-treated THP-1 cells by more than 50%.
      Furthermore, mutation of the two cleavage sites in LANA led to a significant
      increase in IL-1beta production in transfected THP-1 cells; this provides
      evidence that these sites function to blunt the inflammasome, which is known to
      be activated in latently infected PEL cells. These results suggest that specific
      caspase cleavage sites in KSHV LANA function to blunt apoptosis as well as
      interfere with the caspase-1-mediated inflammasome, thus thwarting key cellular
      defense mechanisms.

PMID- 26218606
TI  - Calmodulin and Ca(2+) control of voltage gated Na(+) channels.
AB  - The structures of the cytosolic portion of voltage activated sodium channels
      (CTNav) in complexes with calmodulin and other effectors in the presence and the
      absence of calcium provide information about the mechanisms by which these
      effectors regulate channel activity. The most studied of these complexes, those
      of Nav1.2 and Nav1.5, show details of the conformations and the specific contacts
      that are involved in channel regulation. Another voltage activated sodium
      channel, Nav1.4, shows significant calcium dependent inactivation, while its
      homolog Nav1.5 does not. The available structures shed light on the possible
      localization of the elements responsible for this effect. Mutations in the genes
      of these 3 Nav channels are associated with several disease conditions: Nav1.2,
      neurological conditions; Nav1.4, syndromes involving skeletal muscle; and Nav1.5,
      cardiac arrhythmias. Many of these disease-specific mutations are located at the
      interfaces involving CTNav and its effectors. 

PMID- 26218608
TI  - Designing Synthetic Microcapsules That Undergo Biomimetic Communication and
      Autonomous Motion.
AB  - Inspired by the collective behavior of slime molds and amoebas, we designed
      synthetic cell-like objects that move and self-organize in response to self
      generated chemical gradients, thereby exhibiting autochemotaxis. Using
      computational modeling, we specifically focused on microcapsules that encompass a
      permeable shell and are localized on an adhesive surface in solution. Lacking any
      internal machinery, these spherical, fluid-filled shells might resemble the
      earliest protocells. Our microcapsules do, however, encase particles that can
      diffuse through the outer shell and into the surrounding fluid. The released
      particles play two important, physically realizable roles: (1) they affect the
      permeability of neighboring capsules and (2) they generate adhesion gradients on
      the underlying surface. Due to feedback mechanisms provided by the released
      particles, the self-generated adhesion gradients, and hydrodynamic interactions,
      the capsules undergo collective, self-sustained motion and even exhibit antlike
      tracking behavior. With the introduction of a chemically patterned stripe on the
      surface, a triad of capsules can be driven to pick up four-capsule cargo,
      transport this cargo, and drop off this payload at a designated site. We also
      modeled a system where the released particles give rise to a particular cycle of
      negative feedback loops (mimicking the "repressilator" network), which regulates
      the production of chemicals within the capsules and hence their release into the
      solution. By altering the system parameters, three capsules could be controllably
      driven to self-organize into a stable, close-packed triad that would either
      translate as a group or remain stationary. Moreover, the stationary triads could
      be made to switch off after assembly and thus produce minimal quantities of
      chemicals. Taken together, our models allow us to design a rich variety of self
      propelled structures that achieve complex, cooperative behavior through
      fundamental physicochemical phenomena. The studies can also shed light on factors
      that enable individual protocells to communicate and self-assemble into larger
      communities. 

PMID- 26218611
TI  - Controlled Three-Dimensional Hierarchical Structuring by Memory-Based, Sequential
      Wrinkling.
AB  - This paper describes how a memory-based, sequential wrinkling process can
      transform flat polystyrene sheets into multiscale, three-dimensional hierarchical
      textures. Multiple cycles of plasma-mediated skin growth followed by directional
      strain relief of the substrate resulted in hierarchical architectures with
      characteristic generational (G) features. Independent control over wrinkle
      wavelength and wrinkle orientation for each G was achieved by tuning plasma
      treatment time and strain-relief direction for each cycle. Lotus-type
      superhydrophobicity was demonstrated on three-dimensional G1-G2-G3 hierarchical
      wrinkles as well as tunable superhydrophilicity on these same substrates after
      oxygen plasma. This materials system provides a general approach for
      nanomanufacturing based on bottom-up sequential wrinkling that will benefit a
      diverse range of applications and especially those that require large area
      (>cm(2)), multiscale, three-dimensional patterns. 

PMID- 26218615
TI  - Algebraic Error Based Triangulation and Metric of Lines.
AB  - Line triangulation, a classical geometric problem in computer vision, is to
      determine the 3D coordinates of a line based on its 2D image projections from
      more than two views of cameras with known projection matrices. Compared to point
      features, line segments are more robust to matching errors, occlusions, and image
      uncertainties. In addition to line triangulation, a better metric is needed to
      evaluate 3D errors of line triangulation. In this paper, the line triangulation
      problem is investigated by using the Lagrange multipliers theory. The main
      contributions include: (i) Based on the Lagrange multipliers theory, a formula to
      compute the Plucker correction is provided, and from the formula, a new linear
      algorithm, LINa, is proposed for line triangulation; (ii) two optimal algorithms,
      OPTa-I and OPTa-II, are proposed by minimizing the algebraic error; and (iii) two
      metrics on 3D line space, the orthogonal metric and the quasi-Riemannian metric,
      are introduced for the evaluation of line triangulations. Extensive experiments
      on synthetic data and real images are carried out to validate and demonstrate the
      effectiveness of the proposed algorithms. 

PMID- 26218609
TI  - Bi-photon spectral correlation measurements from a silicon nanowire in the
      quantum and classical regimes.
AB  - The growing requirement for photon pairs with specific spectral correlations in
      quantum optics experiments has created a demand for fast, high resolution and
      accurate source characterisation. A promising tool for such characterisation uses
      classical stimulated processes, in which an additional seed laser stimulates
      photon generation yielding much higher count rates, as recently demonstrated for
      a chi(2) integrated source in A. Eckstein et al. Laser Photon. Rev. 8, L76
      (2014). In this work we extend these results to chi(3) integrated sources,
      directly measuring for the first time the relation between spectral correlation
      measurements via stimulated and spontaneous four wave mixing in an integrated
      optical waveguide, a silicon nanowire. We directly confirm the speed-up due to
      higher count rates and demonstrate that this allows additional resolution to be
      gained when compared to traditional coincidence measurements without any increase
      in measurement time. As the pump pulse duration can influence the degree of
      spectral correlation, all of our measurements are taken for two different pump
      pulse widths. This allows us to confirm that the classical stimulated process
      correctly captures the degree of spectral correlation regardless of pump pulse
      duration, and cements its place as an essential characterisation method for the
      development of future quantum integrated devices.

PMID- 26218614
TI  - Correction: Migratory Patterns of Wild Chinook Salmon Oncorhynchus tshawytscha
      Returning to a Large, Free-Flowing River Basin.

PMID- 26218618
TI  - Fetal Growth, Obesity, and Atopic Disorders in Adolescence: a Retrospective Birth
      Cohort Study.
AB  - BACKGROUND: Developmental status at birth and subsequent obesity have been
      implicated in the development of childhood atopic dermatitis (AD) and allergic
      rhinitis (AR). METHODS: The current study analysed the cohort data of 74 688
      junior high school students from a national retrospective birth cohort study in
      Taiwan. A random 10% sample was selected from singleton livebirths with complete
      data on the analytical variables of interest. Atopic disorders, including AD and
      AR, were assessed by questionnaires (International Study of Asthma and Allergies
      in Childhood). Logistic regression analyses were applied with adjustments for
      related risk factors. RESULTS: Among subjects mainly 13-15 years of age, the
      estimated prevalence was 7.6% for AD and 22.4% for AR. While the role of fetal
      growth in allergic disorders was less evident, the risk of developing AD and AR
      were both influenced by a combination of fetal growth status and adolescent body
      mass index (BMI). Compared with those with normal fetal growth and school-aged
      BMI, the risk of developing AD increased 64% among adolescents with both
      restricted fetal growth and high BMI (odds ratio 1.64, 95% confidence interval
      1.37, 1.97). The risk for this combination was higher than that for either
      restricted fetal growth or high BMI alone. Nevertheless, the overall interaction
      between BMI and fetal growth status on atopic disorders did not reach statistical
      significance. CONCLUSIONS: Excessive weight gain could be an important risk
      factor related to developing atopic dermatitis and allergic rhinitis during
      adolescence, especially among infants born small for gestational age.

PMID- 26218621
TI  - Surgery is cost-effective treatment for young patients with vestibular
      schwannomas: decision tree modeling of surgery, radiation, and observation.
AB  - OBJECT: Vestibular schwannomas (VSs) are managed in 3 ways: observation ("wait
      and scan"); Gamma Knife surgery (GKS); or microsurgery. Whereas there is
      considerable literature regarding which management approach is superior, there
      are only a few studies addressing the cost of treating VSs, and there are no cost
      utility analyses in the US to date. METHODS: In this study, the authors used the
      University of California at San Francisco medical record and hospital accounting
      databases to determine total hospital charges and costs for 33 patients who
      underwent open surgery, 42 patients who had GKS, and 12 patients who were
      observed between 2010 and 2013. The authors then performed decision-tree analysis
      to determine which treatment paradigm produces the highest quality-adjusted life
      years and to calculate the incremental cost-effectiveness ratio, depending on the
      patient's age at VS diagnosis. RESULTS: The average total hospital cost over a 3
      year period for surgically treated patients was $80,074 (+/- $49,678) versus
      $9737 (+/- $5522) for patients receiving radiosurgery and $1746 (+/- $2792) for
      patients who were observed. When modeling the most debilitating symptoms and
      worst outcomes of VSs (vertigo and death) at different ages at diagnosis,
      radiation is dominant to observation at all ages up to 70 years. Surgery is cost
      effective when compared with radiation (incremental cost-effectiveness ratio <
      $150,000) at younger ages at diagnosis (< 45 years old). CONCLUSIONS: In this
      model, surgery is a cost-effective alternative to radiation when VS is diagnosed
      in patients at < 45 years. For patients >= 45 years, radiation is the most cost
      effective treatment option.

PMID- 26218610
TI  - Technique for a stapled anastomosis following transanal total mesorectal excision
      for rectal cancer.
AB  - AIM: Transanal total mesorectal excision (taTME) is an emerging and exciting new
      technique in rectal cancer surgery. As with all novel techniques, new challenges
      arise, requiring small modifications of the technique. Here we present a simple
      technique that we have devised to facilitate a stapled anastomosis using standard
      circular staplers following a taTME. METHOD: We describe the technique in a
      stepwise fashion with picture - and video illustration. Our experience with this
      anastomosis in a small cohort of patients is reported. RESULTS: No anastomotic
      leaks occurred in 12 consecutive patients using this technique following taTME.
      In one patient a small defect was noticed on direct visualisation of the
      anastomosis intra-operative, and was closed transanally. So far 8/12 patient had
      their protective ileostomy reversed with satisfactory function. CONCLUSION: We
      believe that this technique for a transanal, stapled anastomosis after a
      transanal TME procedure is safe and reproducible. Objective assessment of
      longterm functional outcome is required and outcomes need to be compared to other
      stapled techniques and handsewn anastomoses.

PMID- 26218617
TI  - Physical activity predicts quality of life and happiness in children and
      adolescents with cerebral palsy.
AB  - PURPOSE: To examine the associations between physical activity, health-related
      quality of life and happiness in young people with cerebral palsy. METHOD: A
      total of 70 young people with cerebral palsy (45 males, 25 females; mean age 13
      years 11 months, SD 2 years 0 month) took part in a cross-sectional, descriptive
      postal survey assessing physical activity (Physical Activity Questionnaire for
      Adolescents), functional ability (Gross Motor Function Classification System),
      quality of life (Pediatric Quality of Life Inventory 4.0) and happiness (single
      Likert-scale item). Relationships between physical activity, quality of life and
      happiness were examined using backward stepwise linear regression. RESULTS:
      Physical activity significantly predicted physical quality of life (R(2 )= 0.64,
      beta = 6.12, p = 0.02), social quality of life (R(2 )= 0.28, beta = 9.27, p <
      0.01) and happiness (R(2 )= 0.08, beta = 0.9, p = 0.04). Physical activity was
      not associated with emotional or school quality of life. CONCLUSIONS: This study
      found a positive association between physical activity, social and physical
      quality of life, and happiness in young people with cerebral palsy. Findings
      underscore the potential benefits of physical activity for the wellbeing of young
      people with cerebral palsy, in addition to its well-recognised physical and
      health benefits. IMPLICATIONS FOR REHABILITATION: Physical activity is a key
      predictor of quality of life and happiness in young people with cerebral palsy.
      Physical activity is widely recognised as having physical health benefits for
      young people with cerebral palsy; however, this study also highlights that it may
      have important benefits for wellbeing, quality of life and happiness. This
      emphasises the need for clinical services and intervention studies aimed
      specifically at increasing physical activity amongst children and adolescents
      with cerebral palsy.

PMID- 26218612
TI  - A diagnostic model for impending death in cancer patients: Preliminary report.
AB  - BACKGROUND: Several highly specific bedside physical signs associated with
      impending death within 3 days for patients with advanced cancer were recently
      identified. A diagnostic model for impending death based on these physical signs
      was developed and assessed. METHODS: Sixty-two physical signs were systematically
      documented every 12 hours from admission to death or discharge for 357 patients
      with advanced cancer who were admitted to acute palliative care units (APCUs) at
      2 tertiary care cancer centers. Recursive partitioning analysis was used to
      develop a prediction model for impending death within 3 days with admission data.
      The model was validated with 5 iterations of 10-fold cross-validation, and the
      model was also applied to APCU days 2 to 6. RESULTS: For the 322 of 357 patients
      (90%) with complete data for all signs, the 3-day mortality rate was 24% on
      admission. The final model was based on 2 variables (Palliative Performance Scale
      [PPS] and drooping of nasolabial folds) and had 4 terminal leaves: PPS score <=
      20% and drooping of nasolabial folds present, PPS score <= 20% and drooping of
      nasolabial folds absent, PPS score of 30% to 60%, and PPS score >= 70%. The 3-day
      mortality rates were 94%, 42%, 16%, and 3%, respectively. The diagnostic accuracy
      was 81% for the original tree, 80% for cross-validation, and 79% to 84% for
      subsequent APCU days. CONCLUSIONS: Based on 2 objective bedside physical signs, a
      diagnostic model was developed for impending death within 3 days. This model was
      applicable to both APCU admission and subsequent days. Upon further external
      validation, this model may help clinicians to formulate the diagnosis of
      impending death.

PMID- 26218619
TI  - Comparing a single case to a control group - Applying linear mixed effects models
      to repeated measures data.
AB  - In neuropsychological research, single-cases are often compared with a small
      control sample. Crawford and colleagues developed inferential methods (i.e., the
      modified t-test) for such a research design. In the present article, we suggest
      an extension of the methods of Crawford and colleagues employing linear mixed
      models (LMM). We first show that a t-test for the significance of a dummy coded
      predictor variable in a linear regression is equivalent to the modified t-test of
      Crawford and colleagues. As an extension to this idea, we then generalized the
      modified t-test to repeated measures data by using LMMs to compare the
      performance difference in two conditions observed in a single participant to that
      of a small control group. The performance of LMMs regarding Type I error rates
      and statistical power were tested based on Monte-Carlo simulations. We found that
      starting with about 15-20 participants in the control sample Type I error rates
      were close to the nominal Type I error rate using the Satterthwaite approximation
      for the degrees of freedom. Moreover, statistical power was acceptable.
      Therefore, we conclude that LMMs can be applied successfully to statistically
      evaluate performance differences between a single-case and a control sample. 

PMID- 26218625
TI  - Does Treatment of Ocular Myasthenia Gravis With Early Immunosuppressive Therapy
      Prevent Secondarily Generalization and Should It Be Offered to All Such Patients?

PMID- 26218620
TI  - Progressive cortical visual failure associated with occipital calcification and
      coeliac disease with relative preservation of the dorsal 'action' pathway.
AB  - We describe the first reported case of a patient with coeliac disease and
      cerebral occipital calcification who shows a progressive and seemingly selective
      failure to recognise visual stimuli. This decline was tracked over a study period
      of 22 years and occurred in the absence of primary sensory or widespread
      intellectual impairment. Subsequent tests revealed that although the patient was
      unable to use shape and contour information to visually identify objects, she was
      nevertheless able to use this information to reach, grasp and manipulate objects
      under central, immediate vision. This preservation of visuo-motor control was
      echoed in her day-to-day ability to navigate and live at home independently. We
      conclude that occipital calcification following coeliac disease can lead to
      prominent higher visual failure that, under prescribed viewing conditions, is
      consistent with separable mechanisms for visual perception and action control. 

PMID- 26218626
TI  - Asymmetric Papilledema in Idiopathic Intracranial Hypertension: Response.

PMID- 26218613
TI  - Ant groups optimally amplify the effect of transiently informed individuals.
AB  - To cooperatively transport a large load, it is important that carriers conform in
      their efforts and align their forces. A downside of behavioural conformism is
      that it may decrease the group's responsiveness to external information.
      Combining experiment and theory, we show how ants optimize collective transport.
      On the single-ant scale, optimization stems from decision rules that balance
      individuality and compliance. Macroscopically, these rules poise the system at
      the transition between random walk and ballistic motion where the collective
      response to the steering of a single informed ant is maximized. We relate this
      peak in response to the divergence of susceptibility at a phase transition. Our
      theoretical models predict that the ant-load system can be transitioned through
      the critical point of this mesoscopic system by varying its size; we present
      experiments supporting these predictions. Our findings show that efficient group
      level processes can arise from transient amplification of individual-based
      knowledge. 

PMID- 26218627
TI  - Dielectric Polarization and Electric Displacement in Polar-Molecule Reactions.
AB  - The aim of this work is to investigate the dielectric polarization in polar
      molecule reactions in the liquid phase theoretically. On the basis of the
      modified Smoluchowski equation, the analytic expression of the polarization is
      derived. The result shows that the expression of the polarization in polar
      molecule reactions is quite different from the one in the Debye model. For
      general reactions, two vectors, the rotational diffusion vector and the component
      concentration vector, are proposed to describe the polarization. For fast
      reactions, the conception of relative permittivity will be nonexistent due to the
      effect of the component concentration vector on the frequency of the applied
      field, and the dielectric behavior may only be analyzed in the time domain. On
      the contrary, for slow reactions, the relative permittivity will be concentration
      dependent. 

PMID- 26218616
TI  - Synthetic biology approaches to engineer T cells.
AB  - There is rapidly growing interest in learning how to engineer immune cells, such
      as T lymphocytes, because of the potential of these engineered cells to be used
      for therapeutic applications such as the recognition and killing of cancer cells.
      At the same time, our knowhow and capability to logically engineer cellular
      behavior is growing rapidly with the development of synthetic biology. Here we
      describe how synthetic biology approaches are being used to rationally alter the
      behavior of T cells to optimize them for therapeutic functions. We also describe
      future developments that will be important in order to construct safe and precise
      T cell therapeutics. 

PMID- 26218624
TI  - Targeting CD64 mediates elimination of M1 but not M2 macrophages in vitro and in
      cutaneous inflammation in mice and patient biopsies.
AB  - Macrophages are key players in controlling the immune response that can adapt to
      microenvironmental signals. This results in distinct polarization states
      (classical M1 or alternative M2), that play a differential role in immune
      regulation. In general, the M1 contribute to onset of inflammation, whereas the
      M2 orchestrate resolution and repair, whereby failure to switch from
      predominantly M1 to M2 reinforces a pro-inflammatory environment and chronic
      inflammation. Here, we show selective elimination of M1 macrophages in vitro by a
      range of CD64-targeted immunotoxins, including H22(scFv)-ETA'. After re
      polarization of already polarized macrophages, still only M1 polarization showed
      sensitivity toward CD64-directed immunotoxins. The selectivity for M1 was found
      linked to reduced endosomal protease activity in M1 macrophages as demonstrated
      by inhibition of endosomal proteases. Using the H22(scFv)-ETA' in a transgenic
      mouse model for chronic cutaneous inflammation, the M1 specificity was confirmed
      in vivo and a beneficial effect on inflammation demonstrated. Also ex vivo on
      skin biopsies from atopic dermatitis and diabetes type II patients with
      chronically-inflamed skin, a clear M1 specific effect was found. This indicates
      the potential relevance for human application. Our data show that targeting M1
      macrophages through CD64 can be instrumental in developing novel intervention
      strategies for chronic inflammatory conditions. 

PMID- 26218622
TI  - Bimodal Imaging of Inflammation with SPECT/CT and MRI Using Iodine-125 Labeled
      VCAM-1 Targeting Microparticle Conjugates.
AB  - Upregulation of cell adhesion molecules on endothelial cells is a hallmark of
      inflammation and an early feature of several neurological conditions. Here, we
      describe bimodal in vivo imaging of this inflammatory event in the brain using
      functionalized micron-sized particles of iron oxide. The particles were
      conjugated to anti-VCAM-1 antibodies and subsequently labeled with iodine-125.
      Radiolabeling of the antibody-coated particles was straightforward and proceeded
      in high radiochemical yields using commercially available iodination tubes. The
      corresponding contrast agent was evaluated in a rat model of cerebral
      inflammation based on intracerebral injection of tumor necrosis factor alpha and
      a rat model of status epilepticus. Biodistribution studies and phosphorimaging of
      cryosections were used to verify in vivo imaging data obtained with single photon
      emission computed tomography (SPECT) and magnetic resonance imaging (MRI). The
      contrast agent showed rapid and highly localized binding to the vasculature of
      inflamed brain tissue, and was effectively cleared from the blood pool within 2
      min postinjection. Overall, the pattern of hypointensities observed with MRI was
      in good agreement with the distribution of the contrast agent as determined with
      SPECT and phosphorimaging; however, conspicuous differences in the signal
      intensities were observed. The results demonstrate that radiolabeled micron-sized
      particles of iron oxide enable multimodal in vivo imaging with MRI and nuclear
      techniques, and highlight the value of validating different imaging methods
      against one another. 

PMID- 26218630
TI  - The Individualised versus the Public Health Approach to Treating Ebola.
AB  - Tom Boyles reflects on differing approaches taken for treating patients with
      Ebola virus disease in low- and high-resource settings. 

PMID- 26218631
TI  - Is Amine a Stronger Base in Ionic Liquid Than in Common Molecular Solvent? An
      Accurate Basicity Scale of Amines.
AB  - The equilibrium basicities of 21 frequently used amines in two room-temperature
      ionic liquids (RTILs) were measured precisely. The standard deviation was much
      superior to that sparsely reported elsewhere. The data comparisons revealed that
      amines are stronger bases in ionic ligquids than in DMSO and water but weaker
      base than in acetonitrile (AN). Interestingly, regression analyses demonstrate
      that the basicity scales obtained in two RTILs correlate well with that in AN but
      not with those in water and DMSO. 

PMID- 26218628
TI  - Characterization of vitamin-cisplatin-loaded chitosan nano-particles for
      chemoprevention and cancer fatigue.
AB  - CONTEXT: Vitamins have been shown to reduce chemotherapy-related fatigue (CRF) by
      conserving energy loss both during and after cancer treatment. However, it
      remains unknown whether this reduction of fatigue interferes with the cancer
      drugs or alters the effectiveness of these agents. OBJECTIVES: The objective was
      to synthesize vitamin-cisplatin-loaded chitosan nano-particles for
      chemoprevention and cancer fatigue. MATERIALS AND METHODS: Multi-vitamin (C, D3,
      and B12)-cisplatin composite nano-formulation called NanoCisVital (NCV) to
      overcome CRF. The interactions between vitamins and NCV were characterized using
      scanning electron microscopy (SEM), Fourier transform infrared (FT-IR)
      spectroscopy, and a particle size analyser. The chemo-preventive activity was
      performed by in vitro bio assays. RESULTS: SEM analysis showed spherical shape
      and the size is < 225 nm. NCV inhibited the proliferating yeast cells as well as
      denaturation of bovine serum albumin, and it also reduced the sprouting of new
      blood vessels in dose-dependent manner. CONCLUSION: Collectively, these results
      demonstrate that the NCV particles can be used to reduce CRF without much
      affecting the anti-cancer properties of cisplatin.

PMID- 26218632
TI  - Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms in oral
      squamous cell carcinoma in south-east Iran.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) gene encodes an essential
      enzyme involving in folate metabolism. Due to the role of folate in DNA
      integrity, polymorphisms of MTHFR are interesting targets for cancer risk
      studies. Our goal was to evaluate the prevalence of MTHFR C677T and A1298T single
      nucleotide polymorphisms in oral squamous cell carcinoma (OSCC). METHODS: The
      study was conducted on 57 OSCC patients diagnosed within 2004-2013 along with 62
      non-OSCC subjects. DNA was extracted by standard kit protocol. Subsequently,
      tetra-ARMS (amplification refractory mutation system)-PCR was applied to identify
      the selected polymorphisms. RESULTS: Data showed that CT and TT genotypes of
      C677T polymorphisms significantly increased the risk of OSCC [odds ratio (OR) =
      2.2, 95% CI: 1-5, P = 0.04]. Although allelic distribution was not significantly
      different between patients and controls, T allele of C677T polymorphism was
      closely associated with the risk of OSCC (OR = 2.5; 95% CI: 0.9-6.9; P = 0.07).
      Results indicated that C677T/A1298C: CC/AC and C677T/A1298C: CC/AA haplotypes
      were the most common combinations in OSCC patient and control groups,
      respectively. (OR = 1.5, 95% CI: 0.6-3.8, P > 0.05). CONCLUSION: Our results
      highlight the possible impact of C677T polymorphism in increasing the risk of
      OSCC development.

PMID- 26218629
TI  - Small Molecule Inhibitors of 8-Oxoguanine DNA Glycosylase-1 (OGG1).
AB  - The DNA base excision repair (BER) pathway, which utilizes DNA glycosylases to
      initiate repair of specific DNA lesions, is the major pathway for the repair of
      DNA damage induced by oxidation, alkylation, and deamination. Early results from
      clinical trials suggest that inhibiting certain enzymes in the BER pathway can be
      a useful anticancer strategy when combined with certain DNA-damaging agents or
      tumor-specific genetic deficiencies. Despite this general validation of BER
      enzymes as drug targets, there are many enzymes that function in the BER pathway
      that have few, if any, specific inhibitors. There is a growing body of evidence
      that suggests inhibition of 8-oxoguanine DNA glycosylase-1 (OGG1) could be useful
      as a monotherapy or in combination therapy to treat certain types of cancer. To
      identify inhibitors of OGG1, a fluorescence-based screen was developed to analyze
      OGG1 activity in a high-throughput manner. From a primary screen of ~50,000
      molecules, 13 inhibitors were identified, 12 of which were hydrazides or acyl
      hydrazones. Five inhibitors with an IC50 value of less than 1 MUM were chosen for
      further experimentation and verified using two additional biochemical assays.
      None of the five OGG1 inhibitors reduced DNA binding of OGG1 to a 7,8-dihydro-8
      oxoguanine (8-oxo-Gua)-containing substrate, but all five inhibited Schiff base
      formation during OGG1-mediated catalysis. All of these inhibitors displayed a
      >100-fold selectivity for OGG1 relative to several other DNA glycosylases
      involved in repair of oxidatively damaged bases. These inhibitors represent the
      most potent and selective OGG1 inhibitors identified to date.

PMID- 26218636
TI  - The first disease connection for Cav2.2 channels.
AB  - Commentary to: CACNA1B mutation is linked to unique myoclonus-dystonia syndrome.
      (Hum. Mol. Genet. 2015, pp. 987-993). 

PMID- 26218634
TI  - Genetic subtypes of invasive bladder cancer.
AB  - PURPOSE OF REVIEW: Recently completed cancer genomics projects identified
      intrinsic subtypes in muscle-invasive bladder cancers. Here we will describe the
      studies that led to their discovery and review their biological and clinical
      properties. RECENT FINDINGS: Whole genome mRNA expression profiling and
      unsupervised hierarchical cluster analyses identified intrinsic basal and luminal
      subtypes in muscle-invasive bladder cancers that are similar to the ones found in
      breast cancer. Tumors within each subtype have distinct responses to conventional
      cisplatin-based combination chemotherapy, and they contain gene expression
      signatures and DNA alterations that may render them vulnerable to clinically
      available targeted therapies. SUMMARY: Like their breast cancer counterparts,
      basal bladder cancers are characterized by poor clinical outcomes in the absence
      of effective systemic therapy, but a large fraction of them do respond to
      neoadjuvant chemotherapy, suggesting that the tumors should be managed
      aggressively. On the contrary, tumors that belong to the 'p53-like' subtype tend
      to be chemoresistant, so patients with these tumors should probably be managed
      differently. It seems likely that prospective identification of tumor intrinsic
      subtype membership could complement the use of DNA-based biomarkers to identify
      the groups of patients who will benefit the most from chemotherapy and targeted
      agents.

PMID- 26218633
TI  - Serum Proenkephalin A Levels and Mortality After Long-Term Follow-Up in Patients
      with Type 2 Diabetes Mellitus (ZODIAC-32).
AB  - BACKGROUND: Two previous studies concluded that proenkephalin A (PENK-A) had
      predictive capabilities for stroke severity, recurrent myocardial infarction,
      heart failure and mortality in patients with stroke and myocardial infarction.
      OBJECTIVES: This study aimed to investigate the value of PENK-A as a biomarker
      for predicting mortality in patients with type 2 diabetes mellitus. METHODS:
      Patients with type 2 diabetes mellitus were included from the prospective
      observational ZODIAC (Zwolle Outpatient Diabetes project Integrating Available
      Care) study. The present analysis incorporated two ZODIAC cohorts (1998 and
      2001). Since blood was drawn for 1204 out of 1688 patients (71%), and information
      on relevant confounders was missing in 47 patients, the final sample comprised
      1157 patients. Cox proportional hazard models were used for evaluating the
      relationship between PENK-A and (cardiovascular) mortality. Risk prediction
      capabilities were assessed with Harrell's C statistics and the integrated
      discrimination improvement (IDI). RESULTS: After a follow-up period of 14 years,
      525 (45%) out of 1157 patients had died, of which 224 (43%) were attributable to
      cardiovascular factors. Higher Log PENK-A levels were not independently
      associated with increased (cardiovascular) mortality. Patients with PENK-A values
      in the highest tertile had a 49% (95%CI 1%-121%) higher risk of cardiovascular
      mortality compared to patients in the reference category (lowest tertile). C
      values were not different after removing PENK-A from the Cox models and there
      were no significant differences in IDI values. CONCLUSIONS: The associations
      between PENK-A and mortality were strongly attenuated after accounting for all
      traditional risk factors. Furthermore, PENK-A did not seem to have additional
      value beyond conventional risk factors when predicting all-cause and
      cardiovascular mortality.

PMID- 26218637
TI  - Salvage of nicotinamide adenine dinucleotide plays a critical role in the
      bioenergetic recovery of post-hypoxic cardiomyocytes.
AB  - BACKGROUND AND PURPOSE: Ischaemic heart disease can lead to serious, life
      threatening complications. Traditional therapies for ischaemia aim to increase
      oxygen delivery and reduce the myocardial ATP consumption by increasing the
      coronary perfusion and by suppressing cardiac contractility, heart rate or blood
      pressure. An adjunctive treatment option for ischaemia is to improve or optimize
      myocardial metabolism. EXPERIMENTAL APPROACH: Metabolic suppression in the
      ischaemic heart is characterized by reduced levels of high-energy molecules: ATP
      and NAD(+) . Because NAD(+) is required for most metabolic processes that
      generate ATP, we hypothesized that restoration of NAD(+) would be a prerequisite
      for ATP regeneration and examined the role of the major NAD(+) anabolic and
      catabolic pathways in the bioenergetic restoration process following oxygen
      glucose deprivation injury in a cardiomyocyte cell line (H9c2 cells). KEY
      RESULTS: Salvage of NAD(+) via nicotinamide phosphoribosyl transferase was
      essential for bioenergetic recovery in cardiomyocytes. Blockade of nicotinamide
      phosphoribosyl transferase prevented the restoration of the cellular ATP pool
      following oxygen-glucose deprivation injury by inhibiting both the aerobic and
      anaerobic metabolism in the cardiomyocytes. NAD(+) consumption by PARP-1 also
      undermined the recovery processes, and PARP inhibition significantly improved the
      metabolism and increased cellular ATP levels in cardiomyocytes. CONCLUSIONS AND
      IMPLICATIONS: We conclude that the NAD(+) salvage pathway is essential for
      bioenergetic recovery in post-hypoxic cardiomyocytes and PARP inhibition may
      represent a potential future therapeutic intervention in ischaemic heart disease.

PMID- 26218641
TI  - Human bone morphogenetic protein 7 transfected nucleus pulposus cells delay the
      degeneration of intervertebral disc in dogs.
AB  - The main reason for intervertebral disc (IVD) degeneration is the decrease in the
      quantity and activity of IVD cells with subsequent reduction of the extracellular
      matrix (ECM). In this study, we investigated a cell-based repair strategy by
      injecting nucleus pulposus cells (NPCs) transduced with human bone morphogenetic
      protein (hBMP7) by adeno-associated virus-2 into the canine degenerative IVD to
      determine whether NPCs expressing hBMP7 could delay the degeneration of the IVD.
      Fourteen canines received annular punctures to induce disc degeneration. Eight
      weeks later, saline (group A), allogeneic NPCs (group B), or allogeneic NPCs
      transduced with hBMP7 (group C) were injected into the degenerative discs. Twelve
      weeks after the injection, MRI scan showed that the degeneration process of
      groups C was slower and less severe compared with that of groups B and C. The IVD
      stability in group C was superior to that in groups A and B in left-right bending
      and rotation. HE, safranin-O staining, and ELISA indicated that the degenerative
      degree of the IVD in group C was significantly milder than that in groups A and
      B. The study demonstrated that the implantation of NPCs-hBMP7 could effectively
      maintained the structural integrity, ECM, and biomechanical properties of the
      canine degenerated discs. (c) 2017 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res 35:1311-1322, 2017.

PMID- 26218638
TI  - Multiparametric Cell Cycle Analysis Using the Operetta High-Content Imager and
      Harmony Software with PhenoLOGIC.
AB  - High-content imaging is a powerful tool for determining cell phenotypes at the
      single cell level. Characterising the effect of small molecules on cell cycle
      distribution is important for understanding their mechanism of action especially
      in oncology drug discovery but also for understanding potential toxicology
      liabilities. Here, a high-throughput phenotypic assay utilising the PerkinElmer
      Operetta high-content imager and Harmony software to determine cell cycle
      distribution is described. PhenoLOGIC, a machine learning algorithm within
      Harmony software was employed to robustly separate single cells from cell clumps.
      DNA content, EdU incorporation and pHH3 (S10) expression levels were subsequently
      utilised to separate cells into the various phases of the cell cycle. The assay
      is amenable to multiplexing with an additional pharmacodynamic marker to assess
      cell cycle changes within a specific cellular sub-population. Using this
      approach, the cell cycle distribution of gammaH2AX positive nuclei was determined
      following treatment with DNA damaging agents. Likewise, the assay can be
      multiplexed with Ki67 to determine the fraction of quiescent cells and with BrdU
      dual labelling to determine S-phase duration. This methodology therefore provides
      a relatively cheap, quick and high-throughput phenotypic method for determining
      accurate cell cycle distribution for small molecule mechanism of action and drug
      toxicity studies. 

PMID- 26218640
TI  - Immobilization, Regiospecificity Characterization and Application of Aspergillus
      oryzae Lipase in the Enzymatic Synthesis of the Structured Lipid 1,3-Dioleoyl-2
      Palmitoylglycerol.
AB  - The enzymatic synthesis of 1,3-dioleoyl-2-palmitoylglycerol (OPO), one of the
      main components of human milk fats, has been hindered by the relatively high cost
      of sn-1,3-specific lipases and the deficiency in biocatalyst stability. The sn
      1,3-specific lipase from Aspergillus oryzae (AOL) is highly and efficiently
      immobilized with the polystyrene-based hydrophobic resin D3520, with a
      significant 49.54-fold increase in specific lipase activity compared with the AOL
      powder in catalyzing the synthesis of OPO through the acidolysis between palm
      stearin and oleic acid (OA). The optimal immobilization conditions were
      investigated, including time course, initial protein concentration and solution
      pH. The sn-1,3 specificity of lipases under different immobilization conditions
      was evaluated and identified as positively associated with the lipase activity,
      and the pH of the immobilization solution influenced the regiospecificity and
      synthetic activity of these lipases. Immobilized AOL D3520, as the biocatalyst,
      was used for the enzymatic synthesis of the structured lipid OPO through the
      acidolysis between palm stearin and OA. The following conditions were optimized
      for the synthesis of structured lipid OPO: 65  degrees C temperature; 1:8
      substrate molar ratio between palm stearin and OA; 8% (w/w) enzyme load; 3.5%
      water content of the immobilized lipase; and 1 h reaction time. Under these
      conditions, highly efficient C52 production (45.65%) was achieved, with a
      tripalmitin content of 2.75% and a sn-2 palmitic acid (PA) proportion of 55.08%
      in the system. 

PMID- 26218639
TI  - The impairment of learning and memory and synaptic loss in mouse after chronic
      nitrite exposure.
AB  - The objective of this study is to understand the impairment of learning and
      memory in mouse after chronic nitrite exposure. The animal model of nitrite
      exposure in mouse was created with the daily intubation of nitrite in adult
      healthy male mice for 3 months. Furthermore, the mouse's learning and memory
      abilities were tested with Morris water maze, and the expression of Synaptophysin
      and gamma-Synuclein was visualized with immunocytochemistry and Western blot. Our
      results showed that nitrite exposure significantly prolonged the escape latency
      period (ELP) and decreased the values of the frequency across platform (FAP) as
      well as the accumulative time in target quadrant (ATITQ) compared to control, in
      dose-dependent manner. In addition, after nitrite exposure, synaptophysin (SYN)
      positive buttons in the visual cortex was reduced, in contrast the increase of
      gamma-synuclein positive cells. The results above were supported by Western blot
      as well. We conclude that nitrite exposure could lead to a decline in mice's
      learning and memory. The overexpression of gamma-synuclein contributed to the
      synaptic loss, which is most likely the cause of learning and memory impairment.
      (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1720-1730, 2016.

PMID- 26218647
TI  - Pulmonary Function and Clinical Manifestations of Patients Infected with Mild
      Influenza A Virus Subtype H1N1: A One-Year Follow-Up.
AB  - OBJECTIVE: To investigate the long-term effects of mild H1N1 influenza infection
      on the pulmonary function of a cohort of patients. METHODS: Forty-eight patients,
      all diagnosed with influenza A virus subtype H1N1 in 2009, were retrospectively
      included in this study. Each patient in the study was monitored for 11-13 months
      by standard pulmonary function examination. The examination included monitoring
      respiratory tract infection symptoms (cough, expectoration or gasping) and vital
      signs. Long-term changes in symptoms and changes in vital signs were correlated
      back to and compared with the severity of the initial H1N1 influenza infection.
      RESULTS: One year post discharge, mild to moderate pulmonary dysfunction was
      observed in the majority of patients. Further, 54.2% of patients had signs of
      severe abnormal pulmonary function, including diffusion disorder (33.3%) and
      small airway dysfunction (33.3%). Fourteen patients presented with respiratory
      tract infection symptoms; 12 with abnormal pulmonary function and two with normal
      pulmonary function. Our results indicated that the change in pulmonary function
      at one year post discharge was not significantly correlated with the severity of
      H1N1 influenza. CONCLUSION: Signs and symptoms of abnormal pulmonary function
      accompanied by respiratory tract infection symptoms remain for some patients
      after one year following discharge from the hospital for mild influenza A virus
      subtype H1N1 infection. These patients should continue to be monitored for any
      changes in condition and symptoms and rehabilitation treatment should be provided
      when necessary.

PMID- 26218655
TI  - A unique 3D metal-organic framework based on a 12-connected pentanuclear Cd(II)
      cluster exhibiting proton conduction.
AB  - Solvothermal reaction of a TCA (TCA = 4,4',4''-tricarboxytriphenylamine) ligand
      with Cd(NO3)2 yielded a unique 3D 12-connected metal-organic framework of , which
      can be simplified as a (3,3,12)-connected 3-nodal net with a Schlafli symbol of
      {4(16).6(36).8(14)}{4(2).6}2{4(3)}2 based on a 12-connected node of a
      pentanuclear Cd(ii) cluster and a three-connected organic linker of TCA. Compound
      exhibits both photoluminescence and proton conductivity. The luminescence
      properties of originate from the triphenylamine chromophore of the TCA ligand.
      The proton conductivity of is supposed to be relevant to the structure attributes
      of . On the one hand, the curved narrow channels lined with a hydrophilic
      pentanuclear Cd(ii) cluster in can improve the water affinity of framework and
      facilitate the water absorption under humid conditions. On the other hand, the
      coordinated water molecules within the pentanuclear Cd(ii) cluster can produce a
      mobile H(+) proton due to coordination activation. At 80  degrees C and 85% RH
      (relative humidity), compound shows the proton conductivity of 1.45 * 10(-6) S
      cm(-1). 

PMID- 26218646
TI  - Towards a Spatial Understanding of Trade-Offs in Sustainable Development: A Meso
      Scale Analysis of the Nexus between Land Use, Poverty, and Environment in the Lao
      PDR.
AB  - In land systems, equitably managing trade-offs between planetary boundaries and
      human development needs represents a grand challenge in sustainability oriented
      initiatives. Informing such initiatives requires knowledge about the nexus
      between land use, poverty, and environment. This paper presents results from Lao
      PDR, where we combined nationwide spatial data on land use types and the
      environmental state of landscapes with village-level poverty indicators. Our
      analysis reveals two general but contrasting trends. First, landscapes with paddy
      or permanent agriculture allow a greater number of people to live in less poverty
      but come at the price of a decrease in natural vegetation cover. Second, people
      practising extensive swidden agriculture and living in intact environments are
      often better off than people in degraded paddy or permanent agriculture. As
      poverty rates within different landscape types vary more than between landscape
      types, we cannot stipulate a land use-poverty-environment nexus. However, the
      distinct spatial patterns or configurations of these rates point to other
      important factors at play. Drawing on ethnicity as a proximate factor for
      endogenous development potentials and accessibility as a proximate factor for
      external influences, we further explore these linkages. Ethnicity is strongly
      related to poverty in all land use types almost independently of accessibility,
      implying that social distance outweighs geographic or physical distance. In turn,
      accessibility, almost a precondition for poverty alleviation, is mainly
      beneficial to ethnic majority groups and people living in paddy or permanent
      agriculture. These groups are able to translate improved accessibility into
      poverty alleviation. Our results show that the concurrence of external influences
      with local-highly contextual-development potentials is key to shaping outcomes of
      the land use-poverty-environment nexus. By addressing such leverage points, these
      findings help guide more effective development interventions. At the same time,
      they point to the need in land change science to better integrate the
      understanding of place-based land indicators with process-based drivers of land
      use change. 

PMID- 26218644
TI  - Allergenic Can f 1 and its human homologue Lcn-1 direct dendritic cells to induce
      divergent immune responses.
AB  - Why and when the immune system skews to Th2 mediated allergic immune responses is
      still poorly characterized. With two homologous lipocalins, the major respiratory
      dog allergen Can f 1 and the human endogenous, non-allergenic Lipocalin-1, we
      investigated their impact on human monocyte-derived dendritic cells (DC). The two
      lipocalins had differential effects on DC according to their allergenic
      potential. Compared to Lipocalin-1, Can f 1 persistently induced lower levels of
      the Th1 skewing maturation marker expression, tryptophan breakdown and
      interleukin (IL)-12 production in DC. As a consequence, T cells stimulated by DC
      treated with Can f 1 produced more of the Th2 signature cytokine IL-13 and lower
      levels of the Th1 signature cytokine interferon-gamma than T cells stimulated by
      Lipocalin-1 treated DC. These data were partially verified by a second pair of
      homologous lipocalins, the cat allergen Fel d 4 and its putative human homologue
      major urinary protein. Our data indicate that the crosstalk of DC with lipocalins
      alone has the potential to direct the type of immune response to these particular
      antigens. A global gene expression analysis further supported these results and
      indicated significant differences in intracellular trafficking, sorting and
      antigen presentation pathways when comparing Can f 1 and Lipocalin-1 stimulated
      DC. With this study we contribute to a better understanding of the induction
      phase of a Th2 immune response. 

PMID- 26218645
TI  - SLC9A3R1 stimulates autophagy via BECN1 stabilization in breast cancer cells.
AB  - Autophagy, a self-catabolic process, has been found to be involved in abrogating
      the proliferation and metastasis of breast cancer. SLC9A3R1 (solute carrier
      family 9, subfamily A [NHE3, cation proton antiporter 3], member 3 regulator 1),
      a multifunctional scaffold protein, is involved in suppressing breast cancer
      cells proliferation and the SLC9A3R1-related signaling pathway regulates the
      activation of autophagy processes. However, the precise regulatory mechanism and
      signaling pathway of SLC9A3R1 in the regulation of autophagy processes in breast
      cancer cells remains unknown. Here, we report that the stability of BECN1, the
      major component of the autophagic core lipid kinase complex, is augmented in
      SLC9A3R1-overexpressing breast cancer MDA-MB-231 cells, subsequently stimulating
      autophagy by attenuating the interaction between BECN1 and BCL2. Initially, we
      found that SLC9A3R1 partially stimulated autophagy through the PTEN-PI3K-AKT1
      signaling cascade in MDA-MB-231 cells. SLC9A3R1 then attenuated the interaction
      between BECN1 and BCL2 to stimulate the autophagic core lipid kinase complex.
      Further findings revealed that SLC9A3R1 bound to BECN1 and subsequently blocked
      ubiquitin-dependent BECN1 degradation. And the deletion of the C-terminal domain
      of SLC9A3R1 resulted in significantly reduced binding to BECN1. Moreover, the
      lack of C-terminal of SLC9A3R1 neither reduced the ubiquitination of BECN1 nor
      induced autophagy in breast cancer cells. The decrease in BECN1 degradation
      induced by SLC9A3R1 resulted in the activity of autophagy stimulation in breast
      cancer cells. These findings indicate that the SLC9A3R1-BECN1 signaling pathway
      participates in the activation of autophagy processes in breast cancer cells. 

PMID- 26218648
TI  - A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox-sensitive
      biodegradable macromolecular MRI contrast agent.
AB  - This work aims to develop safe and effective gadolinium (III)-based biodegradable
      macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral
      polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and
      characterized. In addition to studying the in vitro degradation of GOLS, its
      kinetic stability was also investigated in an in vivo model. The efficacy of GOLS
      for contrast-enhanced MRI was examined with female BALB/c mice bearing 4T1 breast
      cancer xenografts. The pharmacokinetics, biodistribution, and metabolism of GOLS
      were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa
      with T1 relaxivities of 7.20 mM(-1) s(-1) per Gd at 1.5 T, and 6.62 mM(-1) s(-1)
      at 7.0 T. GOLS had high kinetic inertness against transmetallation with Zn(2+)
      ions, and its polymer backbone was readily cleaved by L-cysteine. The agent
      showed improved efficacy for blood pool and tumor MR imaging. The structural
      effect on biodistribution and in vivo chelation stability was assessed by
      comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd
      DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS
      showed high in vivo chelation stability and minimal tissue deposition of
      gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising
      polymeric contrast agent for clinical MR cardiovascular imaging and cancer
      imaging.

PMID- 26218656
TI  - Computer simulation of orthodontic tooth movement using CT image-based voxel
      finite element models with the level set method.
AB  - Orthodontic tooth movement (OTM) is an adaptive biomechanical response of
      dentoalveolar components to orthodontic forces, in which remodeling of the
      alveolar bone occurs in response to changes in the surrounding mechanical
      environment. In this study, we developed a framework for OTM simulation by
      combining an image-based voxel finite element method, with a surface-tracking
      level set method using three-dimensional computer models. For a case study to
      demonstrate its capability of expressing clinical tooth movement, we observed
      displacement and rotation of the tooth under three types of force conditions. The
      simulation results demonstrate that the proposed simulation method has the
      potential to predict clinical OTM. 

PMID- 26218649
TI  - Guaianolides and a seco-Eudesmane from the Resinous Exudates of Cushion Bush
      (Leucophyta brownii) and Evaluation of Their Cytostatic and Anti-inflammatory
      Activity.
AB  - A detailed phytochemical investigation of a dichloromethane extract of the
      resinous exudates of the cushion bush plant (Leucophyta brownii) resulted in the
      isolation of the new 8,12-guaianolides leucophytalins A (5) and B (6), the new
      1,10-seco-eudesmane leucophytalin C (10), six rare 8,12-guaianolides (1-4, 7, and
      8), and the xanthanolide tomentosin (9). The structures of all isolated compounds
      were elucidated on the basis of spectroscopic and spectrometric analyses. The
      structures of compounds isolated in crystalline form, including leucophytalins A
      and C, were further confirmed by X-ray crystallography. The crude extract
      exhibited moderate cytostatic activity against a breast cancer (MCF-7) and human
      colon cancer (HT-29) cell line with IC50 values of 9.3 and 18 MUg/mL,
      respectively, and anti-inflammatory activity against the macrophage-like cell
      line RAW 264.7 with IC50 values of 3.9 and 6.1 MUg/mL for thromboxane B2 and
      prostaglandin E2 production, respectively. The isolated compounds were evaluated
      for their cytostatic activity against MCF-7 and HT-29 cells (1, 3-10) and their
      anti-inflammatory activity against RAW 264.7 cells (1-10). All isolated compounds
      are most likely derived from (+)-germacrene A, and a biosynthetic pathway is
      proposed for these sesquiterpenoids.

PMID- 26218652
TI  - Synthesis, leishmanicidal, trypanocidal and cytotoxic activity of quinoline
      hydrazone hybrids.
AB  - Cutaneous leishmaniasis and Chagas disease are vector-borne parasitic disease
      causing serious risks to million people living in poverty-stricken areas. Both
      diseases are a major health problem in Latin America, and currently drugs for the
      effective treatment of these diseases have important concerns related with
      efficacy or toxicity than need to be addressed. We report herein the synthesis
      and biological activities (cytotoxicity, leishmanicidal and trypanocidal
      activities) of ten quinolone-hydrazone hybrids. The structure of the products was
      elucidated by spectrometric analyses. The synthesized compounds were evaluated
      against amastigotes forms of L. (V) panamensis which is the most prevalent
      Leishmania species in Colombia and Trypanosoma cruzi that is the major pathogenic
      species to humans; in turn, cytotoxicity was evaluated against human U-937
      macrophages. Compounds 6b, 6c and 8 showed activity against L. (V) panamensis
      with EC50 of 6.5 +/- 0.8 MUg/mL (21.2 MUM), 0.8 +/- 0.0 MUg/mL (2.6 MUM) and 3.4
      +/- 0.6 MUg/mL (11.1 MUM), respectively, while compounds 6a and 6c had activity
      against T. cruzi. with EC50 values of 1.4 +/- 0.3 MUg/mL (4.8 MUM) and 6.6 +/-
      0.3 MUg/mL (4.6 MUM), respectively. Even compound 6a showed better activity
      against T. cruzi than the standard drug benznidazole with EC50 = 10.5 +/- 1.8
      MUg/mL (40.3 MUM). Analysis of the results obtained against leishmaniasis
      indicates that antiparasite activity is related to the presence of 2-substituted
      quinoline (isoquinolinic core) and the hydroxyl group in positions 3 and 4 of the
      aromatic ring. Although the majority of these compounds were highly cytotoxic,
      the antiparasite activity was higher than cytotoxicity and therefore, they still
      have potential to be considered as hit molecules for leishmanicidal and
      trypanocidal drug development.

PMID- 26218651
TI  - Synthesis and in vitro characterization of novel fluorinated derivatives of the
      TSPO 18 kDa ligand SSR180575.
AB  - SSR180575 (1) is a high-affinity (0.83 nM) TSPO 18 kDa ligand belonging to the
      pyridazino[4,5-b]indole-1-acetamides family. Herein we describe the synthesis and
      in vitro characterization of two series of new fluorinated analogues. Eleven
      compounds (out of fifteen) displayed nanomolar to subnamolar affinities (0.30-8.1
      nM) and high selectivities (Ki(CBR)/Ki(TSPO) > 10(3)). Two derivatives stand out
      as promising candidates for drug development or use as PET probes for in vivo
      neuroinflammation imaging, once fluorine-18-labelled. 

PMID- 26218650
TI  - Discovery and optimization of adamantane carboxylic acid derivatives as potent
      diacylglycerol acyltransferase 1 inhibitors for the potential treatment of
      obesity and diabetes.
AB  - We have developed a series of adamantane carboxylic acid derivatives exhibiting
      potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activities.
      Optimization of the series led to the discovery of E-adamantane carboxylic acid
      compound 43c, which showed excellent in vitro activity with an IC50 value of 5 nM
      against human and mouse DGAT1, also good druggability as well as microsomal
      stability and safety profiles such as hERG, CYP and cytotoxicity. Compound 43c
      significantly reduced plasma triglyceride levels in vivo (in rodents and
      zebrafish) and also showed bodyweight gain reduction and glucose area under curve
      (AUC) lowering efficacy in diet-induced obesity (DIO) mice. 

PMID- 26218659
TI  - Efficacy of chemically characterized Foeniculum vulgare Mill seed essential oil
      in protection of raw tobacco leaves during storage against fungal and aflatoxin
      contamination.
AB  - AIMS: To report fungal and aflatoxin contamination in stored tobacco leaves and
      the potential of Foeniculum vulgare (fennel) seed essential oil (EO) as a plant
      based preservative in protection of tobacco during storage. METHODS AND RESULTS:
      Mycological analysis of tobacco samples was done by surface sterilization and
      serial dilution tests. The Aspergillus flavus isolates were screened for their
      toxigenicity. Both in vivo and in vitro tests were done to evaluate antifungal
      and antiaflatoxigenic efficacy of chemically characterized EO. The mycoflora
      analysis revealed 108 fungal colonies belonging to five genera and nine species.
      All A. flavus isolates were found aflatoxigenic during screening. Gas
      chromatography and mass spectrometry analysis of EO identified 19 components
      (99.66%); estragole being the major component (47.49%). The EO showed broad
      fungitoxicity at 1.25 MUl ml(-1) and 100% inhibition to AFB1 production as well
      as ergosterol synthesis at 1.0 MUl ml(-1) concentration. EO showed 100%
      protection of stored tobacco samples from aflatoxin B1 contamination.
      CONCLUSIONS: The fennel EO can thus be formulated as a plant-based preservative
      for food items. SIGNIFICANCE AND IMPACT OF THE STUDY: The present investigation
      comprises the first report on antiaflatoxin efficacy of fennel oil and its
      potency in the protection of tobacco leaves from fungal and aflatoxin
      contamination during storage.

PMID- 26218658
TI  - A Time Series Study of Lophelia pertusa and Reef Megafauna Responses to Drill
      Cuttings Exposure on the Norwegian Margin.
AB  - As hotspots of local biodiversity in the deep sea, preservation of cold-water
      coral reef communities is of great importance. In European waters the most
      extensive reefs are found at depths of 300 - 500 m on the continental margin. In
      Norwegian waters many of these reefs are located in areas of interest for oil and
      gas exploration and production. In this study drilling was carried out in the
      Morvin drill field in proximity to a number of small Lophelia pertusa coral reefs
      (closest reefs 100 m upstream and 350 m downstream of point of waste drill
      material release). In a novel monitoring study, ROV video surveys of 9 reefs were
      conducted prior, during, immediately after and >1 year after drilling operations.
      Behavior of coral polyps inhabiting reefs exposed to differing concentrations of
      drill cuttings and drilling fluids (waste drilling material) were compared.
      Levels of expected exposure to these waste materials were determined for each
      reef by modelling drill cutting transport following release, using accurate in
      situ hydrodynamic data collected during the drilling period and drill cutting
      discharge data as parameters of a dispersal model. The presence / absence of
      associate reef species (Acesta excavata, Paragorgia arborea and Primnoa
      resedaeformis) were also determined from each survey video. There were no
      significant differences in Lophelia pertusa polyp behavior in corals modelled to
      have been exposed to pulses of >25 ppm drill cutting material and those modelled
      to be exposed to negligible concentrations of material. From the video data
      collected, there were no observed degradations of reef structure over time, nor
      reductions of associate fauna abundance, regardless of modelled exposure
      concentration at any of the surveyed reefs. This study focused exclusively on
      adult fauna, and did not assess the potential hazard posed by waste drilling
      material to coral or other larvae. Video data was collected by various ROV's,
      using different camera and lighting setups throughout the survey campaign, making
      comparison of observations prior, during and post drilling problematic. A
      standardization of video monitoring in future monitoring campaigns is
      recommended. 

PMID- 26218654
TI  - Mechanisms of hypervirulent Clostridium difficile ribotype 027 displacement of
      endemic strains: an epidemiological model.
AB  - Following rapid, global clonal dominance of hypervirulent ribotypes, Clostridium
      difficile now constitutes the primary infectious cause of nosocomial diarrhoea.
      Evidence indicates at least three possible mechanisms of hypervirulence that
      facilitates the successful invasion of these atypical strains: 1) increased
      infectiousness relative to endemic strains; 2) increased symptomatic disease rate
      relative to endemic strains; and 3) an ability to outcompete endemic strains in
      the host's gut. Stochastic simulations of an infection transmission model
      demonstrate clear differences between the invasion potentials of C. difficile
      strains utilising the alternative hypervirulence mechanisms, and provide new
      evidence that favours certain mechanisms (1 and 2) more than others (3).
      Additionally, simulations illustrate that direct competition between strains
      (inside the host's gut) is not a prerequisite for the sudden switching that has
      been observed in prevailing ribotypes; previously dominant C. difficile strains
      can be excluded by hypervirulent ribotypes through indirect (exploitative)
      competition. 

PMID- 26218653
TI  - Design, synthesis, in-vitro antiproliferative activity and kinase profile of new
      picolinamide based 2-amido and ureido quinoline derivatives.
AB  - New 2-amido and ureido quinoline derivatives substituted with 2-N-methylamido
      pyridin-4-yloxy group at the 5-position of quinoline (18 final compounds) have
      been designed and synthesized as anticancer sorafenib congeners. Among the
      synthesized derivatives, fourteen compounds were selected for evaluation of their
      antiproliferative activity over a panel of 60 cancer cell lines at a single dose
      concentration of 10 MUM at National Cancer Institute (NCI, USA). Four compounds,
      9b-d and 9f showed promising mean growth inhibitions and thus were further tested
      at five-dose testing mode to determine their IC50 values. The data revealed that
      2,4-difluorophenyl (9b) and 4-chloro-3-trifluoromethylphenyl (9d) urea compounds
      are the most active derivatives with significant efficacies and superior
      potencies than sorafenib in 36 and 12 cancer cell lines, respectively, belonging
      particularly to renal carcinoma cell (RCC), ovarian, and non small cell lung
      cancer (NSCL). Compound 9b and 9d were found to be six and two times more potent
      than sorafenib against A498 RCC line, with IC50 values of 0.42 MUM and 1.36 MUM,
      respectively. Accordingly, compound 9d was screened over a panel of 41 oncogenic
      kinases at a single dose concentration of 10 MUM to profile its kinase inhibitory
      activity. Interestingly, the compound showed highly selective inhibitory
      activities ( 81.8% and 96.3%) against BRAF(V600E) and C-RAF kinases with IC50
      values of 316 nM and 61 nM, respectively. In addition, molecular docking, cell
      cycle analysis, compliance to Lipinski's rule of five, and in silico toxicity
      assessment have been reported. 

PMID- 26218661
TI  - Associations and Synergistic Effects for Psychological Distress and Chronic Back
      Pain on the Utilization of Different Levels of Ambulatory Health Care. A Cross
      Sectional Study from Austria.
AB  - The aim of this analysis was to assess the impact of chronic back pain and
      psychological distress on the utilization of primary and secondary levels of care
      in the ambulatory health care sector in Austria - a country without a gatekeeping
      system. Additionally, we aimed to determine if the joint effect of chronic back
      pain and psychological distress was higher than the impact of the sum of the two
      single conditions. The database used for this analysis was the Austrian Health
      Interview Survey, with data from 15,474 individuals. Statistical methods used
      were descriptive tests, regression models and the calculation of synergistic
      effects. Both chronic back pain and psychological distress had a positive
      association with the utilization of the primary (OR for chronic back pain 1.53
      and psychological distress 1.33) and secondary (OR for chronic back pain 1.32 and
      psychological distress 1.24) levels of the health care sector. In the fully
      adjusted model, the synergistic effect of chronic back pain and psychological
      distress was significant for the secondary level of care (S 1.99, PAF 0.20), but
      not for the primary level of care (S 1.16, PAF 0.07). Synergistic effects and
      associations for chronic back pain and psychological distress on the utilization
      of both the primary and secondary levels of the ambulatory health care sector
      were observed, particularly for the secondary level of care. Our results
      demonstrate the utilization of health care services settings by individuals with
      these conditions, and offer opportunities to consider reorganization and
      structuring of the Austrian health care system. 

PMID- 26218664
TI  - Salient features of the coronary collateral circulation and its clinical
      relevance.
AB  - The coronary collateral circulation provides an alternative source of blood
      supply to myocardium jeopardised by ischaemia. Collaterals enlarge with
      obstructive coronary artery disease to allow bulk flow, but blood flow
      deliverable by the native, pre-formed collateral extent can already be sizeable.
      Genetic determinants contribute significantly to the wide variability observed in
      both native collateral extent and its capacity to enlarge, and the severity of
      the coronary stenosis is the most significant environmental determinant for
      collateral enlargement. The protective effect of a well-developed coronary
      collateral circulation translates into relevant improvements in all-cause and
      cardiac mortality in the acute and chronic phases of coronary artery disease, as
      well as into a reduction of future adverse cardiovascular events. 

PMID- 26218662
TI  - Accelerating MR Imaging Liver Steatosis Measurement Using Combined Compressed
      Sensing and Parallel Imaging: A Quantitative Evaluation.
AB  - PURPOSE: To determine the limits of agreement of hepatic fat fraction and R2*
      relaxation rate quantified with accelerated magnetic resonance (MR) imaging
      reconstructed with combined compressed sensing and parallel imaging compared with
      conventional fully sampled acquisitions. MATERIALS AND METHODS: Eleven subjects
      with type 2 diabetes and a healthy control subject were recruited with the
      approval of the Newcastle and North Tyneside 2 ethics committee and written
      consent. Undersampled data at ratios of 2.6*, 2.9*, 3.8*, and 4.8* were
      prospectively acquired in addition to fully sampled data by using five gradient
      echoes per repetition time at 3.0 T. Fat fraction maps were calculated by using
      combined compressed sensing and parallel imaging (CS-PI) reconstruction and Bland
      Altman analysis performed to assess bias and 95% limits of agreement. Inter- and
      intrarater analysis was performed for quantitative fat fraction and R2*
      relaxation rate, and image quality was assessed with a four-point scale by two
      independent observers. RESULTS: The fat fractions from the accelerated
      acquisitions had 95% limits of agreement of 1.2%, 1.2%, 1.1%, and 1.5%,
      respectively, with no bias. When compared with the intra- and interrater 95%
      limits of agreement (0.7% and 0.8%), acceleration of up to 3.8* did not greatly
      degrade the fat fraction measurements. No or minimal artifact was detected at
      2.6* and 2.9* accelerations, moderate artifact was detected at 3.8* acceleration,
      and substantial artifact was detected at 4.8* acceleration. CONCLUSION:
      Prospective undersampling and CS-PI reconstruction of liver fat fractions can be
      used to accelerate liver fat fraction measurements. The fat fractions and image
      quality produced were acceptable up to a factor of 3.8*, thereby shortening the
      required breath-hold duration from 17.7 seconds to 4.7 seconds.

PMID- 26218663
TI  - Cyclometalated Platinum(II) Terpyridylacetylide with a Bis(arylamine) Donor as a
      Proton-Triggered Luminescence Chemosensor for Zn(2+).
AB  - A cyclometalated Pt(II) acetylide derivative bearing a bis(arylamine) donor (D)
      and a terpyridine (TPY) receptor (A) was successfully synthesized and
      characterized. This three-component D-pi-A system displays an intense low-energy
      absorption band at lambdamax = 470 nm, resulting from overlapping the dpi(Pt) ->
      pi*(C^N^N) metal-to-ligand charge transfer and pi(C=C-Ar) -> pi*(C^N^N) ligand-to
      ligand charge transfer transitions with the pi(bis(arylamine)) -> pi*(C^N^N)
      intraligand charge transfer transition. Upon protonation of the bis(arylamine)
      donor, a strong emission from the phosphorescence Pt(II) complex unit is
      recovered at lambdamax = 580 nm. With introduction of the TPY receptor, this
      complex possesses quite high affinity for Zn(2+) (Ka = 6.86 * 10(9) mol(
      2).dm(6)) to form the heterotrinuclear Pt-Zn-Pt complex in CH2Cl2 solution.
      Though this coordination effect is seriously inhibited by protons in acidic
      medium, the 2.4-fold luminescence intensity enhancement is obtained yet, strongly
      suggesting the presence of the intramolecular energy transfer process from the
      Zn(II)-TPY complex core to the phosphorescence Pt(II) complex units at two ends.
      The H(+)-triggered and Zn(2+)-enhanced luminescence can be reversibly switched on
      and off upon successive additions of H(+) and OH(-). Furthermore, this complex
      displays an unexpected Zn(2+)-selective luminescence enhancement effect in acidic
      solution. 

PMID- 26218665
TI  - Correction: PPARA Intron Polymorphism Associated with Power Performance in 30-s
      Anaerobic Wingate Test.

PMID- 26218660
TI  - Symbiotic maple saps minimize disruption of the mice intestinal microbiota after
      oral antibiotic administration.
AB  - This study was undertaken to evaluate the in vivo impact of new symbiotic
      products based on liquid maple sap or its concentrate. Sap and concentrate, with
      or without inulin (2%), were inoculated with Bifidobacterium lactis Bb12 and
      Lactobacillus rhamnosus GG valio at initial counts of 2-4 * 10(8) cfu mL(-1). The
      experiments started with intra-gastric administration of antibiotic (kanamycin 40
      mg in 0.1 cc) (to induce microbiota disturbance and/or diarrhea) to 3-to-5-week
      old C57BL/6 female mice followed by a combination of prebiotic and probiotics
      included in the maple sap or its concentrate for a week. The combination inulin
      and probiotics in maple sap and concentrate appeared to minimize the antibiotic
      induced breakdown of mice microbiota with a marked effect on bifidobacterium and
      bacteroides levels, thus permitting a more rapid re-establishment of the baseline
      microbiota levels. Results suggest that maple sap and its concentrate represent
      good candidates for the production of non-dairy functional foods. 

PMID- 26218657
TI  - Loss of C. elegans GON-1, an ADAMTS9 Homolog, Decreases Secretion Resulting in
      Altered Lifespan and Dauer Formation.
AB  - ADAMTS9 is a metalloprotease that cleaves components of the extracellular matrix
      and is also implicated in transport from the endoplasmic reticulum (ER) to the
      Golgi. It has been reported that an ADAMTS9 gene variant is associated with type
      2 diabetes. The underlying pathology of type 2 diabetes is insulin resistance and
      beta-cell dysfunction. However, the molecular mechanisms underlying ADAMTS9
      function in beta cells and peripheral tissues are unknown. We show that loss of
      C. elegans GON-1, an ADAMTS9 homolog, alters lifespan and dauer formation. GON-1
      loss impairs secretion of proteins such as insulin orthologs and TGF-beta, and
      additionally impacts insulin/IGF-1 signaling in peripheral tissues. The function
      of the GON domain, but not the protease domain, is essential for normal lifespan
      and dauer formation in these scenarios. We conclude that the GON domain is
      critical for ADAMTS9/GON-1 function across species, which should help the
      understanding of type 2 diabetes in humans. 

PMID- 26218667
TI  - Heart beat detection using a multimodal data coupling method.
AB  - The most straightforward method for heart beat estimation is R-peak detection
      based on an electrocardiogram (ECG) signal. Current R-peak detection methods do
      not work properly when the ECG signal is contaminated or missing, which leads to
      the incorrect estimation of the heart rate. This raises the need for reliable
      algorithms which can locate heart beats in continuous long-term multimodal data,
      allowing robust analysis.In this paper, three peak detectors are evaluated for
      heart beat detection using various cardiovascular signals. One of the peak
      detectors is a new general peak detector (GPD) algorithm which is applicable on
      ECG and other pulsatile signals to compensate for the limitation of QRS
      detection. This peak detector algorithm is adaptive and independently finds
      amplitude characteristics for every recording, while not tuned for ECG or other
      pulsatile signals. Three strategies, which are different disciplines of
      detectors, are then proposed while the fusion method remains the same in all
      strategies. In the first strategy, the ECG and the lowest-indexed signal of
      general blood pressure (BP), arterial blood pressure (ART) and pulmonary arterial
      pressure (PAP) are processed through gqrs and wabp (from the PhysioNet library),
      respectively. In the second strategy, all beats in different signals are detected
      by GPD. In the third strategy, ECG and other signals are processed by gqrs and
      GPD, respectively. In all three strategies two criteria are used in order to fuse
      the detections. The first criterion is based on the number of candidate
      detections in a specific time period, based on which signals of interest are
      selected. The second fusion criterion is based on the regularity of the derived
      intervals between subsequent candidate detections. If the number of detections in
      ECG and one of BP, ART and PAP signals have reasonable physiological range, a new
      signal is generated in which they are coupled with each other. Heart beats can
      more easily be detected in noisy parts of these signals using the new coupled
      waveform. For instance, if ECG and BP are coupled, BP pulses make the real heart
      beats in noisy parts of ECG detectable and ECG R-peaks make the weak BP pulses
      detectable in the new waveform. The proposed peak detector is developed using the
      MIT/BIH arrhythmia database. Furthermore, heart beat detection strategies were
      evaluated using the train and test datasets of PhysioNet/CinC Challenge (2014),
      and the overall results of the strategies are compared. 

PMID- 26218668
TI  - Catalyst Controlled Divergent C4/C8 Site-Selective C-H Arylation of
      Isoquinolones.
AB  - The catalyst-controlled C4/C8 site-selective C-H arylation of isoquinolones using
      aryliodonium salts as the coupling partners was developed. The C4-selective
      arylation was successfully achieved via an electrophilic palladation pathway. A
      completely different selectivity pattern was observed using an Ir(III) catalytic
      system, which resulted in C-C bond formation exclusively at the C8 position. The
      isoquinolone scaffold can be conveniently equipped with various aryl substituents
      at either the C4 or C8 position. 

PMID- 26218669
TI  - Long-Term Safety of Paliperidone Extended Release in Adolescents with
      Schizophrenia: An Open-Label, Flexible Dose Study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the long-term safety and
      tolerability of paliperidone extended-release (ER) in adolescents with
      schizophrenia. METHODS: This was a 2 year open-label, multicenter study in
      adolescents (12-17 years of age, inclusive) with schizophrenia. Eligible patients
      were initially treated with 6 mg/day paliperidone ER, and the dose could be
      adjusted between 1.5 and 12 mg/day based on clinical need. Safety parameters were
      treatment-emergent adverse events (TEAEs), weight, Tanner staging, blood
      chemistry (including prolactin, glucose, insulin, and lipid levels), and
      extrapyramidal symptom (EPS) scales. The main efficacy end-point was change from
      baseline to endpoint in Positive and Negative Syndrome Scale for Schizophrenia
      (PANSS) total score. RESULTS: Of 400 enrolled patients (mean age, 15.4 years;
      boys, 61%), 220 were completers. Median (range) exposure was 604.5 (2-765) days.
      TEAEs were reported in 85.3% of patients; most frequently reported TEAEs included
      somnolence, increased weight, headache, insomnia, nasopharyngitis, akathisia,
      schizophrenia exacerbation, and tremor. No deaths were reported. There were no
      clinically significant mean changes in growth-adjusted z score for change in
      weight, height, or body mass index (BMI). Tanner ratings showed normal
      maturation. Most frequently occurring EPS-related events were related to
      Parkinsonism (15.5%) and hyperkinesia (13.8%). No cases of tardive dyskinesia
      were reported. Hyperprolactinemia (based on laboratory values) was noted in 56%
      of patients and 9.3% of patients had prolactin-related TEAEs. A low percentage of
      patients (4.3%, n=14) had a shift from normal or impaired fasting glucose to high
      levels. Mean (SD) decrease (improvement) in PANSS total score from baseline to
      end-point was -19.1 (21.89). The majority of patients had a >=20% improvement in
      PANSS total score (responders) from initial treatment with paliperidone ER.
      Overall, 41.7% of patients achieved remission during the study. CONCLUSIONS:
      Paliperidone ER was generally tolerable, and exhibited efficacy in the
      maintenance treatment of schizophrenia in adolescents in this large 2 year study.

PMID- 26218666
TI  - Tools for Successful Weight Management in Primary Care.
AB  - Obesity is one of the most pervasive and costly public health problems.
      Clinicians need effective tools to address weight management in primary care,
      including evaluation and communication methods, guideline-based weight management
      interventions and safe and effective weight loss medications and surgery. The
      objective of this Grand Rounds presentation is to provide practicing clinicians
      with the latest information regarding effective ways to care for and communicate
      with patients about weight loss; evidence-based guidelines for selecting weight
      management therapies and safety, efficacy and adverse effects of weight loss
      medications and surgery. 

PMID- 26218675
TI  - Productivity depends more on the rate than the frequency of N addition in a
      temperate grassland.
AB  - Nitrogen (N) is a key limiting resource for aboveground net primary productivity
      (ANPP) in diverse terrestrial ecosystems. The relative roles of the rate and
      frequency (additions yr(-1)) of N application in stimulating ANPP at both the
      community- and species-levels are largely unknown. By independently manipulating
      the rate and frequency of N input, with nine rates (from 0 to 50 g N m(-2) year(
      1)) crossed with two frequencies (twice year(-1) or monthly) in a temperate
      steppe of northern China across 2008-2013, we found that N addition increased
      community ANPP, and had positive, negative, or neutral effects for individual
      species. There were similar ANPP responses at the community- or species-level
      when a particular annual amount of N was added either twice year(-1) or monthly.
      The community ANPP was less sensitive to soil ammonium at lower frequency of N
      addition. ANPP responses to N addition were positively correlated with annual
      precipitation. Our results suggest that, over a five-year period, there will be
      similar ANPP responses to a given annual N input that occurs either frequently in
      small amounts, as from N deposition, or that occur infrequently in larger
      amounts, as from application of N fertilizers. 

PMID- 26218672
TI  - Interacting domains in the epithelial sodium channel that mediate proteolytic
      activation.
AB  - Epithelial Sodium Channel (ENaC) proteolysis at sites in the extracellular loop
      of the alpha and gamma subunits leads to marked activation. The mechanism of this
      effect remains debated, as well as the role of the N- and C-terminal fragments of
      these subunits created by cleavage. We introduced cysteines at sites bracketing
      upstream and downstream the cleavage regions in alpha and gamma ENaC to examine
      the role of these fragments in the activated channel. Using thiol modifying
      reagents, as well as examining the effects of cleavage by exogenous proteases we
      constructed a functional model that determines the potential interactions of the
      termini near the cleavage regions. We report that the N-terminal fragments of
      both alpha and gamma ENaC interact with the channel complex; with interactions
      between the N-terminal gamma and the C-terminal alpha fragments being the most
      critical to channel function and activation by exogenous cleavage by subtilisin.
      Positive charge modification at a.a.135 in the N-terminal fragment of gamma
      exhibited the largest inhibition of channel function. This region was found to
      interact with the C-terminal alpha fragment between a.a. 205 and 221; a tract
      which was previously identified to be the site of subtilisin's action. These data
      provide the first evidence for the functional channel rearrangement caused by
      proteolysis of the alpha and gamma subunit and indicate that the untethered N
      terminal fragments of these subunits interact with the channel complex. 

PMID- 26218674
TI  - Long-term anorectal, urinary and sexual dysfunction causing distress after
      radiotherapy for anal cancer: a Danish multicentre cross-sectional questionnaire
      study.
AB  - AIM: The objective of primary radiotherapy for anal cancer is to remove cancer
      while maintaining anorectal function. However, little is known about anorectal
      function among long-term survivors without colostomy. Using a cross-sectional
      questionnaire study, we examined symptoms and distress related to the dysfunction
      of pelvic organs after radiotherapy for anal cancer. METHOD: A questionnaire
      regarding anorectal, urinary and sexual symptoms was sent to anal cancer patients
      without recurrence or colostomy, diagnosed during 1996-2003, and treated with
      curative intent (chemo)radiotherapy at three Danish centres. For each symptom we
      assessed frequency and severity and the level of symptom-induced distress (no,
      little, moderate or great distress). RESULTS: Of 94 eligible patients, 84 (89%)
      returned the completed questionnaire at a median of 33 months after radiotherapy.
      Incontinence for solid stools, liquid stools and gas occurred at least monthly in
      31%, 54% and 79% of patients, respectively. Overall 40% of patients reported
      great distress from incontinence for solid or liquid stools at least monthly.
      Faecal urgency occurring at least monthly was experienced by 87% of patients and
      caused great distress in 43%. Stress, urge or another type of urinary
      incontinence occurred at least monthly in 45% and caused great distress in 21%.
      Urinary urgency occurred at least monthly in 48% but only caused great distress
      in 14%. Sexual desire was severely decreased in 58% and only 24% were satisfied
      with their sexual function. CONCLUSION: Distressing long-term anorectal and
      sexual dysfunction was common after radiotherapy for anal cancer, and morbidity
      due to urinary dysfunction was moderate.

PMID- 26218676
TI  - 4-Methoxycinnamic acid--An unusual phenylpropanoid involved in phenylphenalenone
      biosynthesis in Anigozanthos preissii.
AB  - In vitro root cultures of Anigozanthos preissii and Wachendorfia thyrsiflora
      (Haemodoraceae) are suitable biological systems for studying the biosynthesis of
      phenylphenalenones. Here we report how we used these root cultures to investigate
      precursor-product relationships between phenylpropanoids and phenylphenalenones
      whose phenyl rings share identical substitution patterns. Four phenylpropanoic
      acids, including ferulic acid and the unusual 4-methoxycinnamic acid, were used
      in (13)C-labeled form as substrates to study their incorporation into
      phenylphenalenones. In addition to the previously reported 2-hydroxy-9-(4'
      hydroxy-3'-methoxyphenyl)-1H-phenalen-1-one (trivial name musanolone F), 2
      hydroxy-9-(4'-methoxyphenyl)-1H-phenalen-1-one (proposed trivial name 4'
      methoxyanigorufone) was found as a biosynthetic product in A. preissii. The
      carbon skeleton of 4'-methoxycinnamic acid was biosynthetically incorporated as
      an intact unit including its 4'-O-methyl substituent at the lateral phenyl ring.
      4'-Methoxyanigorufone is reported here for the first time as a natural product. 

PMID- 26218673
TI  - Developing a prototype for short-term psychodynamic (supportive-expressive)
      therapy: An empirical study with the psychotherapy process Q-set.
AB  - OBJECTIVE: A Psychotherapy Process Q-set (PQS) prototype characteristic of short
      term psychodynamic therapy (STPP) does not yet exist. METHOD: Experts in
      supportive-expressive (SE) therapy used the 100-Item PQS questionnaire to rate an
      ideal short-term SE therapy. RESULTS: Agreement between raters was high
      (Cronbach's alpha = 0.94). The prototype for SE therapy showed a significant
      correlation with the psychoanalytic prototype, but with 28% of variance
      explained, the majority of variance of the former was not explained by the latter
      or vice versa. Furthermore, the SE prototype showed significant correlations with
      the cognitive-behavioral prototype and the prototype of interpersonal therapy by
      Ablon and Jones (r = 0.69, 0.43). CONCLUSIONS: We recommend using the PQS
      prototype presented here for future process research on STPP.

PMID- 26218681
TI  - Correction: Identification of Putative ORF5 Protein of Porcine Circovirus Type 2
      and Functional Analysis of GFP-Fused ORF5 Protein.

PMID- 26218683
TI  - Characteristics of chest wall injuries that predict postrecovery pulmonary
      symptoms: A secondary analysis of data from a randomized trial.
AB  - BACKGROUND: Although thoracic trauma is common, little is known about which
      factors lead to poor functional outcomes. We sought to determine which
      characteristics of chest wall injury predict postrecovery pulmonary symptoms or
      health-related quality of life. METHODS: We conducted a secondary analysis of
      data from a randomized trial involving patients with chest wall injuries at a
      Level I trauma center between December 2007 and July 2012. We evaluated the
      overall severity of the chest wall injury-characterized primarily by the number
      of fractured ribs-and rib fracture location (upper, middle, and lower; anterior,
      lateral, and posterior) as predictors of patient-reported outcomes 60 days after
      injury: dyspnea burden (0-40), Modified Medical Research Council Dyspnea Scale
      (MMRC) (0-4), St. George's Respiratory Questionnaire (SGRQ), and normalized
      Medical Outcomes Study Short-Form 36 (SF-36) scores. RESULTS: Of 189 evaluable
      subjects, the mean (SD) number of fractured ribs was 5 (4). The number of
      fractured ribs was not associated with dyspnea burden, MMRC, or SGRQ scores.
      After adjustment for confounders, each additional fractured rib was associated
      with worse SF-36 Physical Functioning and Bodily Pain scores (-0.6 units [95%
      confidence interval (CI), -1.1 to 0.0] and -0.8 units [95% CI, -1.3 to -0.2],
      respectively). Lower rib fractures were associated with worse dyspnea burden (3.4
      units; 95% CI, 1.0-5.9), MMRC score (0.4 units; 95% CI, 0.0-0.8), and SF-36
      Physical Functioning, Role-Physical, Role-Emotional, and Physical Component
      Summary scores (-4 units [95% CI, -8 to 0], -5 units [95% CI, -8 to -1], -4 units
      [95% CI, -8 to 0], and -4 units [95% CI, -7 to -1], respectively). CONCLUSION:
      The overall anatomic severity of chest wall injuries does not predict worse
      dyspnea symptoms 60 days after injury, but it does predict increased patient
      perceptions of pain and physical function limitations. Lower rib fractures
      predict both persistent respiratory symptoms and perception of decreased overall
      health. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

PMID- 26218682
TI  - Rapid Diversity Loss of Competing Animal Species in Well-Connected Landscapes.
AB  - Population viability of a single species, when evaluated with metapopulation
      based landscape evaluation tools, always increases when the connectivity of the
      landscape increases. However, when interactions between species are taken into
      account, results can differ. We explore this issue using a stochastic spatially
      explicit meta-community model with 21 competing species in five different
      competitive settings: (1) weak, coexisting competition, (2) neutral competition,
      (3) strong, excluding competition, (4) hierarchical competition and (5) random
      species competition. The species compete in randomly generated landscapes with
      various fragmentation levels. With this model we study species loss over time.
      Simulation results show that overall diversity, the species richness in the
      entire landscape, decreases slowly in fragmented landscapes whereas in well
      connected landscapes rapid species losses occur. These results are robust with
      respect to changing competitive settings, species parameters and spatial
      configurations. They indicate that optimal landscape configuration for species
      conservation differs between metapopulation approaches, modelling species
      separately and meta-community approaches allowing species interactions. The
      mechanism behind this is that species in well-connected landscapes rapidly
      outcompete each other. Species that become abundant, by chance or by their
      completive strength, send out large amounts of dispersers that colonize and take
      over other patches that are occupied by species that are less abundant. This
      mechanism causes rapid species loss. In fragmented landscapes the colonization
      rate is lower, and it is difficult for a new species to establish in an already
      occupied patch. So, here dominant species cannot easily take over patches
      occupied by other species and higher diversity is maintained for a longer time.
      These results suggest that fragmented landscapes have benefits for species
      conservation previously unrecognized by the landscape ecology and policy
      community. When species interactions are important, landscapes with a low
      fragmentation level can be better for species conservation than well-connected
      landscapes. Moreover, our results indicate that metapopulation based landscape
      evaluation tools may overestimate the value of connectivity and should be
      replaced by more realistic meta-community based tools. 

PMID- 26218679
TI  - Uniaxial Strain Redistribution in Corrugated Graphene: Clamping, Sliding,
      Friction, and 2D Band Splitting.
AB  - Graphene is a promising material for strain engineering based on its excellent
      flexibility and elastic properties, coupled with very high electrical mobility.
      In order to implement strain devices, it is important to understand and control
      the clamping of graphene to its support. Here, we investigate the limits of the
      strong van der Waals interaction on friction clamping. We find that the friction
      of graphene on a SiO2 substrate can support a maximum local strain gradient and
      that higher strain gradients result in sliding and strain redistribution.
      Furthermore, the friction decreases with increasing strain. The system used is
      graphene placed over a nanoscale SiO2 grating, causing strain and local strain
      variations. We use a combination of atomic force microscopy and Raman scattering
      to determine the friction coefficient, after accounting for compression and
      accidental charge doping, and model the local strain variation within the laser
      spot size. By using uniaxial strain aligned to a high crystal symmetry direction,
      we also determine the 2D Raman Gruneisen parameter and deformation potential in
      the zigzag direction. 

PMID- 26218671
TI  - Generation of Naivetropic Induced Pluripotent Stem Cells from Parkinson's Disease
      Patients for High-Efficiency Genetic Manipulation and Disease Modeling.
AB  - The lack of robust Parkinson's disease (PD) phenotype in parkin knockout rodents
      and the identification of defective dopaminergic (DA) neurotransmission in
      midbrain DA neurons derived from induced pluripotent stem cells (iPSC) of PD
      patients with parkin mutations demonstrate the utility of patient-specific iPSCs
      as an effective system to model the unique vulnerabilities of midbrain DA neurons
      in PD. Significant efforts have been directed at developing efficient genomic
      engineering technologies in human iPSCs to study diseases such as PD. In the
      present study, we converted patient-specific iPSCs from the primed state to a
      naivetropic state by DOX-induced expression of transgenes (Oct4, Sox2, Klf4, c
      Myc, and Nanog) and the use of 2iL (MEK inhibitor PD0325901, GSK3 inhibitor
      CHIR99021, and human LIF). These patient-specific naivetropic iPSCs were
      pluripotent in terms of marker expression, spontaneous differentiation in vitro,
      and teratoma formation in vivo. They exhibited morphological, proliferative, and
      clonogenic characteristics very similar to naive mouse embryonic stem cells
      (ESC). The high clonal efficiency and proliferation rate of naivetropic iPSCs
      enabled very efficient gene targeting of GFP to the PITX3 locus by transcription
      activator-like effector nuclease. The naivetropic iPSCs could be readily reverted
      to the primed state upon the withdrawal of DOX, 2iL, and the switch to primed
      state hESC culture conditions. Midbrain DA neurons differentiated from the
      reverted iPSCs retained the original phenotypes caused by parkin mutations,
      attesting to the robustness of these phenotypes and the usefulness of genomic
      engineering in patient-specific naivetropic iPSCs for studying PD. 

PMID- 26218685
TI  - Venous thromboembolic risk assessment models should not solely guide prophylaxis
      and surveillance in trauma patients.
AB  - BACKGROUND: Venous thromboembolism (VTE) risk assessment models exist to stratify
      patients at risk for VTE and guide surveillance and prophylaxis. We evaluated the
      only two models developed specifically for trauma patients: the Trauma Embolic
      Scoring System (TESS) and the Risk Assessment Profile (RAP). METHODS: Clinical
      and demographic data on patients admitted from July 2006 to December 2011 who
      underwent surveillance lower extremity duplex ultrasound were recorded. Patients
      were excluded if they were missing one or more of the variables required to
      calculate either TESS or RAP. Patients received prophylaxis according to American
      College of Chest Physicians guidelines. TESS and RAP scores were calculated
      retrospectively and compared between patients with VTE and patients without VTE.
      High risk was defined by the models as TESS score of 7 or greater and RAP score
      of 5 or greater. RESULTS: A total of 2,868 patients received surveillance lower
      extremity duplex ultrasound. TESS score was calculated for 2,140 patients; 215
      developed VTE, 110 (51%) of whom had TESS score less than 7. The sensitivity and
      specificity at a cutoff point of 7 were 49% and 72%, respectively. RAP score was
      calculated for 1,505 patients; 152 developed VTE, 26 (17%) of whom had RAP score
      of less than 5. The sensitivity and specificity at a cutoff point of 5 were 83%
      and 37%, respectively. The area under the receiver operating characteristic curve
      for each model was 0.66. CONCLUSION: A clinically significant number of patients
      who developed VTE were classified as low risk by both TESS and RAP. The
      indications for VTE surveillance and chemoprophylaxis should not be based
      exclusively on these scores. These results suggest that additional variables
      should be sought to improve risk assessment for VTE following trauma. LEVEL OF
      EVIDENCE: Care management study, level III.

PMID- 26218684
TI  - Pneumomediastinum following blunt trauma: Worth an exhaustive workup?
AB  - BACKGROUND: Incidental pneumomediastinum is a common radiologic finding following
      blunt thoracic injury; however, the clinical significance of pneumomediastinum on
      screening imaging is poorly defined (Curr Probl Surg. 2004;41(3):211-380; Injury.
      2010;41(1):40-43). The purpose of this study was to define the incidence of
      aerodigestive injuries in patients with pneumomediastinum after blunt thoracic
      and neck injury. METHODS: After institutional review board approval was obtained,
      a retrospective review was performed of all patients admitted to Los Angeles
      County + University of Southern California Medical Center with blunt neck and/or
      thoracic injuries between January 2007 and December 2012. All patients with
      pneumomediastinum on radiologic investigation were included. Data accrued
      included demographics, admission clinical data, injury severity patterns,
      incidence of aerodigestive injuries, operative findings, morbidity, mortality, as
      well as intensive care unit and hospital lengths of stay. RESULTS: A total of
      9,946 patients were included in the study. The predominant mechanism was motor
      vehicle collision (49%), disproportionately male (76%). Overall, 258 patients
      (2.6%) had a pneumomediastinum: 65 (25%) and 193 (75%) were diagnosed on a chest
      x-ray or on a computed tomography (CT) scan, respectively. A total of 21 patients
      (8.1%) had an aerodigestive workup with bronchoscopy, esophagram, and/or
      esophagoscopy. Overall, four aerodigestive lesions (1.6%) were diagnosed. Three
      tracheobronchial injuries were identified on CT scan, and one esophageal injury
      was diagnosed on an esophagram. Two tracheobronchial injuries required surgery,
      while the remaining cases were managed nonoperatively. The overall mortality in
      this cohort was 10.9%. CONCLUSION: Isolated findings of pneumomediastinum on
      screening chest x-ray or CT following blunt trauma is a poor predictor of an
      aerodigestive injury. Highly selective workup in this clinical setting is
      warranted. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III;
      therapeutic study, level IV.

PMID- 26218686
TI  - Complete ultrasonography of trauma in screening blunt abdominal trauma patients
      is equivalent to computed tomographic scanning while reducing radiation exposure
      and cost.
AB  - BACKGROUND: Liberal use of computed tomography of the abdomen and pelvis (CTAP)
      in the screening of blunt abdominal trauma (BAT) has heightened concerns for
      increased radiation exposure and costs. We sought to demonstrate that in a select
      group of BAT patients, complete ultrasonography of trauma (CUST) is equivalent to
      routine CTAP but with significantly decreased radiation and costs. METHODS: A
      retrospective analysis of patients screened for BAT from 2000 to 2011 in a Level
      1 trauma center was performed. CUST was available from 8:00 AM to 11:00 PM daily,
      while CTAP was performed thereafter. Decision to perform CTAP or CUST overnight
      was made by the attending surgeon based on clinical examination. False negatives
      (FNs) were described as either a negative CUST or CTAP finding, which later
      required exploratory laparotomy. Medicare rates and previous data were used for
      the estimation of cost and radiation exposure. RESULTS: There were 19,128
      patients screened for BAT. A total of 12,577 patients (65.8%) initially underwent
      CUST, and 6,548 (34.2%) underwent CTAP; 11,059 patients (58% of the total BAT
      patients) avoided a CTAP, yielding an estimated savings of $6.5 million and
      188,003 mSv less radiation during the course of the study. Compared with the CTAP
      group, patients undergoing CUST had lower Injury Severity Score (ISS) (8.1 vs.
      9.6), were older (44.7 years vs. 35.2 years), and experienced less traumatic
      brain injury (61.4% vs. 69.3%) (all with p < 0.002). Mortality was higher in the
      CUST group (1.8% vs. 1.2%, p = 0.02), but it was insignificant when adjusted for
      age older than 65 years (1.1% vs. 0.9%, p = 0.23) or head injury (0.6% and 0.3%,
      p = 0.4). FN CUST and FN CTAP were 0.29% and 0.1%, respectively (p =
      nonsignificant), with similar mortality (20% vs. 0%, p = 0.44). CONCLUSION: CUST
      is equivalent to routine CTAP for BAT screening and leads to an average of 42%
      less radiation exposure and more than $591,000 savings per year. LEVEL OF
      EVIDENCE: Diagnostic study, level IV; therapeutic/care management study, level
      IV.

PMID- 26218680
TI  - Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA
      Helicase and ATP-Independent RNA Chaperone.
AB  - RNA helicases and chaperones are the two major classes of RNA remodeling
      proteins, which function to remodel RNA structures and/or RNA-protein
      interactions, and are required for all aspects of RNA metabolism. Although some
      virus-encoded RNA helicases/chaperones have been predicted or identified, their
      RNA remodeling activities in vitro and functions in the viral life cycle remain
      largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses
      in the Picornaviridae family, which includes numerous important human pathogens.
      Herein, we report that the nonstructural protein 2CATPase of enterovirus 71
      (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and
      has been regarded as the most important neurotropic enterovirus after poliovirus
      eradication, functions not only as an RNA helicase that 3'-to-5' unwinds RNA
      helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA
      chaperone that destabilizes helices bidirectionally and facilitates strand
      annealing and complex RNA structure formation independently of ATP. We also
      determined that the helicase activity is based on the EV71 2CATPase middle
      domain, whereas the C-terminus is indispensable for its RNA chaperoning activity.
      By promoting RNA template recycling, 2CATPase facilitated EV71 RNA synthesis in
      vitro; when 2CATPase helicase activity was impaired, EV71 RNA replication and
      virion production were mostly abolished in cells, indicating that 2CATPase
      mediated RNA remodeling plays a critical role in the enteroviral life cycle.
      Furthermore, the RNA helicase and chaperoning activities of 2CATPase are also
      conserved in coxsackie A virus 16 (CAV16), another important enterovirus.
      Altogether, our findings are the first to demonstrate the RNA helicase and
      chaperoning activities associated with enterovirus 2CATPase, and our study
      provides both in vitro and cellular evidence for their potential roles during
      viral RNA replication. These findings increase our understanding of enteroviruses
      and the two types of RNA remodeling activities. 

PMID- 26218688
TI  - Pediatric solid organ injury operative interventions and outcomes at Harborview
      Medical Center, before and after introduction of a solid organ injury pathway for
      pediatrics.
AB  - BACKGROUND: Although nonoperative management has become the standard of care for
      solid organ injury, variability exists in the care patients receive, and there
      are limited data regarding nonoperative management in patients with high grades
      of organ injury and substantial overall injury. We aimed to evaluate operative
      intervention frequency, including splenectomy, and patient outcomes before and
      after institution of the pediatric solid organ injury pathway at Harborview
      Medical Center (HMC) in 2005. METHODS: This is a retrospective cohort study
      conducted at HMC for all pediatric solid organ injury patients from 2001 to 2012.
      Patients were identified in the Harborview Trauma Registry via DRG International
      Classification of Diseases-9th Rev. (ICD-9) codes for the presence of liver and
      spleen injuries. Demographic information, clinical characteristics, and ICD-9
      procedure codes were also obtained from the trauma registry. Outcomes including
      splenectomy, a related abdominal surgery (exploratory laparotomy, spleen or liver
      repair, or splenectomy), mortality, and length of stay were compared between
      periods before and after 2005, adjusted for Injury Severity Score (ISS). RESULTS:
      The pediatric solid organ injury population at HMC (n = 712) has a high frequency
      of high-grade injury (35% Grade IV or V) and a high level of overall injury
      severity (median ISS, 21). Splenectomy was rare and remained stable over time
      despite an increase in severity of injury (from 2.4% to 0.8%, p = 0.44, among
      patients with isolated injury and from 4.0% to 3.3%, p = 0.78, among patients
      with nonisolated injury). Other abdominal surgeries also remained stable over
      time. Mortality decreased among patients with nonisolated injury (from 11.2% to
      4.8%, p = 0.01). Length of stay decreased among patients with isolated organ
      injury, from a median of 4 days (interquartile range, 3-5 days) to 2 days
      (interquartile range, 2-3 days) (p < 0.0005) as well as within the lower ISS
      strata among patients with nonisolated organ injury (from a median of 4 days to 2
      days among ISS < 12, p = 0.007; from 5 days to 3 days among ISS of 12-20, p =
      0.0001; and from 7 days to 4 days among ISS of 21-33, p = 0.003). CONCLUSION:
      Care in the recent period (2005-2012) was associated with a stable, low frequency
      of splenectomy; decreased mortality for patients with nonisolated injury; and
      decreased hospital length of stay among most subsets of patients, suggesting
      improved care despite an increase in patients' severity of injury. LEVEL OF
      EVIDENCE: Therapeutic study, level IV; epidemiologic study, level III.

PMID- 26218677
TI  - Microbiota and host determinants of behavioural phenotype in maternally separated
      mice.
AB  - Early-life stress is a determinant of vulnerability to a variety of disorders
      that include dysfunction of the brain and gut. Here we exploit a model of early
      life stress, maternal separation (MS) in mice, to investigate the role of the
      intestinal microbiota in the development of impaired gut function and altered
      behaviour later in life. Using germ-free and specific pathogen-free mice, we
      demonstrate that MS alters the hypothalamic-pituitary-adrenal axis and colonic
      cholinergic neural regulation in a microbiota-independent fashion. However,
      microbiota is required for the induction of anxiety-like behaviour and
      behavioural despair. Colonization of adult germ-free MS and control mice with the
      same microbiota produces distinct microbial profiles, which are associated with
      altered behaviour in MS, but not in control mice. These results indicate that MS
      induced changes in host physiology lead to intestinal dysbiosis, which is a
      critical determinant of the abnormal behaviour that characterizes this model of
      early-life stress. 

PMID- 26218689
TI  - Intravenous access in the prehospital settings: What can be learned from point-of
      injury experience.
AB  - BACKGROUND: Intravenous (IV) access has an essential role in the care provided
      for trauma patients, allowing for transfusion of blood products, fluids, and
      drugs. Decisions should be made regarding the necessity of IV access while
      considering cost-benefit of the procedure in terms of delayed evacuation times.
      METHODS: A retrospective review of all trauma patients in whom at least one
      attempt at IV access was performed were reviewed. Data were abstracted from the
      Israeli Defense Force Trauma Registry. RESULTS: Of 7,476 patients, 1,082 patients
      who had at least one documented attempt at IV access between January 1997 and
      April 2013 were included in this study. Overall cumulative success rate at IV
      access was 82%. Success rates for IV access were 86%, 68%, 63%, 50%, 20% for the
      first, second, third, fourth, and fifth attempts, respectively. The first and
      second attempts accounted for 96% of the successful procedures. Mortality in
      patients for whom IV access was successful was 13%; mortality in patients for
      whom IV access was not successful was 35%. CONCLUSION: The success rate of IV
      access declined with each subsequent attempt. There was minimal improvement of
      overall success rate seen after the second attempt. Our findings suggest that the
      inability to obtain peripheral venous access is associated with severe injuries.
      These finding support a policy of limiting the number of venous access attempts
      to two attempts, followed by a reevaluation of need for parenteral access.
      Improved training of combat medics and paramedics might marginally increase the
      success rates of IV access. Point-of-injury data, used for ongoing learning and
      research, form the ground for improving combat casualty care and thus help saving
      lives. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 26218690
TI  - Decreased mortality after prehospital interventions in severely injured trauma
      patients.
AB  - BACKGROUND: We test the hypothesis that prehospital interventions (PHIs)
      performed by skilled emergency medical service providers during ground or air
      transport adversely affect outcome in severely injured trauma patients. METHODS:
      Consecutive trauma activations (March 2012 to June 2013) transported from the
      scene by air or ground emergency medical service providers were reviewed. PHI was
      defined as intubation, needle decompression, tourniquet, cricothyroidotomy, or
      advanced cardiac life support. RESULTS: In 3,733 consecutive trauma activations
      (71% blunt, 25% penetrating, 4% burns), age was 39 years, 74% were male, Injury
      Severity Score (ISS) was 5, and Glasgow Coma Score (GCS) was 15, with 32%
      traumatic brain injury (TBI) and 7% overall mortality. Those who received PHI (n
      = 130, 3.5% of the trauma activations) were more severely injured: ISS (26 vs.
      5), GCS (3 vs. 15), TBI (57% vs. 31%), Revised Trauma Score (RTS, 5.45 vs. 7.84),
      Trauma and Injury Severity Score (TRISS, 1.32 vs. 4.89), and mortality (56% vs.
      5%) were different (all p < 0.05) than those who received no PHI. Air crews
      transported 22% of the patients; more had TBI, blunt injury, high ISS, and long
      prehospital times (all p < 0.05), but mortality was similar to those transported
      by ground. In the most severely injured patients with signs of life who received
      a PHI, the ISS, prehospital times, and proportions of TBI, blunt trauma, and air
      transport were similar, but mortality was significantly lower (43% vs. 23%, p=
      0.021). CONCLUSION: In our urban trauma system, PHIs are associated with a lower
      incidence of mortality in severely injured trauma patients and do not delay
      transport to definitive care. LEVEL OF EVIDENCE: Prognostic/epidemiologic study,
      level III; therapeutic study, level IV.

PMID- 26218692
TI  - Discrete roles of intracellular phospholipases A2 in human neutrophil
      cytotoxicity.
AB  - BACKGROUND: The role of calcium-independent phospholipase A2 (iPLA2), a component
      of the three major PLA2 families, in acute/chronic inflammatory processes remains
      elusive. Previous investigations have documented iPLA2-mediated respiratory burst
      of neutrophils (PMNs); however, the causative isoform of iPLA2 is unidentified.
      We also demonstrated that the iPLA2gamma-specific inhibitor attenuates
      trauma/hemorrhagic shock-induced lung injury. Therefore, iPLA2gamma may be
      implicated in acute inflammation. In addition, arachidonic acid (AA), which is
      primarily produced by cytosolic PLA2 (cPLA2), is known to display PMN
      cytotoxicity, although the relationship between AA and the cytotoxic function is
      still being debated on. We therefore hypothesized that iPLA2gamma regulates PMN
      cytotoxicity via AA-independent signaling pathways. The study aim was to
      distinguish the role of intracellular phospholipases A2, iPLA2, and cPLA2, in
      human PMN cytotoxicity and explore the possibility of the presence of signaling
      molecule(s) other than AA. METHODS: Isolated human PMNs were incubated with the
      PLA2 inhibitor selective for iPLA2beta, iPLA2gamma, or cPLA2 and then activated
      with formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol 12-myristate 13
      acetate (PMA). Superoxide production was assayed according to the superoxide
      dismutase-inhibitable cytochrome c reduction method, and the degree of elastase
      release was measured using a p-nitroanilide-conjugated elastase-specific
      substrate. In addition, chemotaxis toward platelet activating factor/fMLP was
      determined with a modified Boyden chamber system. RESULTS: The iPLA2gamma
      specific inhibitor reduced the fMLP/PMA-stimulated superoxide generation by 90%
      and 30%, respectively; in addition, the inhibitor completely blocked the fMLP/PMA
      activated elastase release. However, the cPLA2-specific inhibitor did not
      abrogate these effects to any degree at all concentrations. Likewise, the
      inhibitor for iPLA2gamma, but not iPLA2beta or cPLA2, completely inhibited the
      platelet activating factor/fMLP-induced chemotaxis. CONCLUSION: iPLA2 is involved
      in extracellular reactive oxygen species production, elastase release, and
      chemotaxis in response to well-defined stimuli. In addition, the ineffectiveness
      of the cPLA2 inhibitor suggests that AA may not be relevant to these cytotoxic
      functions.

PMID- 26218678
TI  - Fludarabine, cyclophosphamide, and multiple-dose rituximab as frontline therapy
      for chronic lymphocytic leukemia.
AB  - BACKGROUND: Fludarabine, cyclophosphamide, and rituximab (FCR) result in durable
      responses in patients with previously untreated chronic lymphocytic leukemia
      (CLL). Previous reports have suggested that in patients with relapsed CLL, a dose
      intensified rituximab regimen increases response rates in comparison with
      standard-dose rituximab. It is unknown whether rituximab intensification of the
      FCR regimen will result in improved response rates and patient outcomes in
      patients with previously untreated CLL. METHODS: A single-arm study was conducted
      to evaluate the safety and efficacy of a modified FCR regimen with multiple-dose
      rituximab (FCR3) in 65 patients with previously untreated CLL. The results were
      compared with those for a historical cohort treated with FCR. RESULTS: The
      overall response rate to FCR3 was 97%, with 75% of the patients achieving a
      complete remission. Minimal residual disease negativity was achieved for 62% of
      the patients according to flow cytometry. The median time to progression (TTP)
      was 81 months, and the median overall survival (OS) was not reached, with 58% of
      the patients still alive at a median survivor follow-up of 9.7 years. Grade 3 or
      4 neutropenia, grade 3 or 4 thrombocytopenia, and major infections were observed
      with 45%, 5%, and 1.9% of the FCR3 courses, respectively. Therapy-related
      myelodysplastic syndrome (t-MDS) or therapy-related acute myelogenous leukemia (t
      AML) developed in 7 patients (11%; P < .01 vs the historical FCR cohort).
      CONCLUSIONS: In patients with previously untreated CLL, FCR3 resulted in response
      rates, TTP, and OS similar to those of a historical cohort of patients treated
      with FCR. FCR3 was associated with an increased incidence of t-MDS/t-AML.

PMID- 26218693
TI  - The therapeutic effect and mechanism of niacin on acute lung injury in a rat
      model of hemorrhagic shock: Down-regulation of the reactive oxygen species
      dependent nuclear factor kappaB pathway.
AB  - BACKGROUND: The purpose of the current study was to investigate the protective
      effect of niacin on acute lung injury by the down-regulation of the nuclear
      factor kappaB (NF-kappaB) pathway in hemorrhagic shock (HS) rats. METHODS: HS was
      induced in male Sprague-Dawley rats by withdrawing blood to maintain a mean
      arterial pressure of 20 mm Hg to 25 mm Hg for 40 minutes. The rats were
      resuscitated by the reinfusion of the drawn blood, and a vehicle (HS), a low-dose
      of niacin (360 mg/kg, HS + LD-NA), or a high dose of niacin (1,080 mg/kg, HS + HD
      NA) were administered orally. The survival of the subjects was observed for 72
      hours, and a separate set of animals was killed at 6 hours after HS induction. We
      measured cytoplasmic phosphorylated inhibitor kappaB-alpha and inhibitor kappaB
      alpha expressions, nuclear NF-kappaB p65 expression, NF-kappaB p65 DNA-binding
      activity, MEK partner 1 activity, tumor necrosis factor alpha (TNF-alpha),
      interleukin 6 (IL-6), IL-8, nicotinamide adenine dinucleotide (NAD+), reduced
      nicotinamide adenine dinucleotide phosphate, reduced glutathione, glutathione
      disulfide, malondialdehyde levels, and histologic damage in the lung tissue. We
      also measured TNF-alpha, IL-6, and IL-8 levels in the serum. RESULTS: The
      survival rates of the sham, HS, HS + LD-NA, and HS + HD-NA groups were 6 of 6
      (100%), 0 of 9 (0%), 1 of 9 (11.1%), and 3 of 9 (33.3%), respectively. A high
      dose of niacin increased lung NAD+, nicotinamide adenine dinucleotide phosphate
      levels, and glutathione-glutathione disulfide ratios; decreased lung
      malondialdehyde levels; down-regulated the NF-kappaB pathway; suppressed TNF
      alpha, IL-6, and IL-8 levels in the lung tissue and serum; and attenuated
      histologic lung damage. CONCLUSION: A high dose of niacin attenuated lung
      inflammation, suppressed proinflammatory cytokine release, reduced histologic
      lung damage, and improved survival after HS in rats. Its therapeutic benefits
      were associated with the down-regulation of the reactive oxygen species-dependent
      NF-kappaB pathway.

PMID- 26218696
TI  - A comparison of Injury Severity Score and New Injury Severity Score after
      penetrating trauma: A prospective analysis.
AB  - BACKGROUND: The Injury Severity Score (ISS) has been validated in numerous
      studies and has become one of the most common trauma scoring systems since its
      inception. The ISS equation was later modified to create the New Injury Severity
      Score (NISS). By using the three most severe injuries regardless of body region,
      the NISS seems well suited to describe patients of penetrating trauma, where
      injuries often cluster within a single body region. We hypothesized that NISS
      would better predict outcomes than ISS in penetrating trauma patients. METHODS:
      An analysis (June 2008 to March 2009) of all severely injured (length of hospital
      stay >= 48 hours, intensive care unit admission, interhospital transfer, or
      death) penetrating trauma patients revealed final study sample of 256 patients.
      ISS and NISS were compared as predictors for both mortality and complications
      through area under the receiver operating characteristic curve, Hanley-McNeil
      test, multiple-variable logistic regression, and Hosmer-Lemeshow goodness-of-fit
      test analysis. RESULTS: Of 256 study patients, 195 (76.2%) survived until
      discharge. The mean (ISS, 21.7 +/- 21.1 vs. NISS, 27.4 +/- 22.0; p < 0.001) and
      median (ISS, 14.0 vs. NISS, 21.0) ISS was lower than those of the NISS. Overall,
      173 patients (67.6%) had discordant scores with 26% and 43% having scores greater
      than 25 (ISS and NISS, respectively, p < 0.01). The mortality area under the
      curve (AUC) for NISS was greater than the AUC for ISS in all penetrating patients
      (0.930 vs. 0.885, p = 0.008), those with penetrating torso injuries (NISS, 0.934
      vs. ISS, 0.881, p < 0.001), and those with severe (score > 25) injuries (NISS,
      0.845 vs. ISS, 0.761, p < 0.001). In patients surviving for more than 48 hours,
      the complications AUC for NISS was also greater than the AUC for ISS (NISS, 0.838
      vs. ISS, 0.784; p = 0.023). CONCLUSION: The NISS outperformed ISS as a predictor
      of both mortality and complications in civilian penetrating trauma patients.
      These results indicate that NISS is a superior scoring system for patients with
      penetrating injuries. LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 26218687
TI  - Management of children with solid organ injuries after blunt torso trauma.
AB  - BACKGROUND: Management of children with intra-abdominal solid organ injuries has
      evolved markedly. We describe the current management of children with intra
      abdominal solid organ injuries after blunt trauma in a large multicenter network.
      METHODS: We performed a planned secondary analysis of a prospective, multicenter
      observational study of children (<18 years) with blunt torso trauma. We included
      children with spleen, liver, or kidney injuries identified by computed
      tomography, laparotomy/laparoscopy, or autopsy. Outcomes included disposition and
      interventions (blood transfusion for intra-abdominal hemorrhage, angiography,
      laparotomy/laparoscopy). We performed subanalyses of children with isolated
      injuries. RESULTS: A total of 12,044 children were enrolled; 605 (5.0%) had intra
      abdominal solid organ injuries. The mean (SD) age was 10.7 (5.1) years, and
      injured organs included spleen 299 (49.4%), liver 282 (46.6%), and kidney 147
      (24.3%). Intraperitoneal fluid was identified on computed tomography in 461 (76%;
      95% confidence interval [CI], 73-80%), and isolated solid organ injuries were
      present in 418 (69%; 95% CI, 65-73%). Treatment included therapeutic laparotomy
      in 17 (4.1%), angiographic embolization in 6 (1.4%), and blood transfusion in 46
      (11%) patients. Laparotomy rates for isolated injury were 11 (5.4%) of 205 (95%
      CI, 2.7-9.4%) at non-freestanding children's hospitals and 6 (2.8%) of 213 (95%
      CI, 1.0-6.0%) at freestanding children's hospitals (difference, 2.6%; 95% CI, 
      7.1% to 12.2%). Dispositions of the 212 children with isolated Grade I or II
      organ injuries were home in 6 (3%), emergency department observation in 9 (4%),
      ward in 114 (54%), intensive care unit in 73 (34%), operating suite in 7 (3%),
      and transferred in 3 (1%) patients. Intensive care unit admission for isolated
      Grade I or II injuries varied by center from 9% to 73%. CONCLUSION: Most children
      with solid organ injuries are managed with observation. Blood transfusion, while
      uncommon, is the most frequent therapeutic intervention; angiographic
      embolization and laparotomy are uncommon. Emergency department disposition of
      children with isolated Grade I to II solid organ injuries is highly variable and
      often differs from published guidelines. LEVEL OF EVIDENCE:
      Prognostic/epidemiologic study, level III; therapeutic study, level IV.

PMID- 26218691
TI  - Tourniquet use for civilian extremity trauma.
AB  - BACKGROUND: Unlike in the military setting, where the use of tourniquets has been
      well established, in the civilian sector their use has been far less uniform. The
      purpose of this study was to examine the outcomes associated with the use of
      tourniquets for civilian extremity trauma. STUDY DESIGN: Adult (>=18 years)
      patients admitted to our institution with an extremity injury requiring
      tourniquet application from January 2007 to June 2014 were retrospectively
      reviewed. The primary outcome analyzed was limb loss. Secondary outcomes included
      death, hospital length of stay, and complications. RESULTS: There were 87
      patients who met inclusion criteria. Average age was 35.3 years, 90.8% were male,
      and 66.7% had penetrating injuries, with a median Injury Severity Score (ISS) of
      6. Tourniquets were placed in the prehospital setting in 50.6%, in the emergency
      department in 39.1%, and in the operating room in 10.3% of patients. The windlass
      type Combat Application Tourniquet was the most commonly used type (67.8%),
      followed by a pneumatic system (24.1%) and self-made tourniquet (8.0%). The
      median duration of use was 75 minutes (interquartile range, 91) with no
      differences between groups (p = 0.547). Overall, 80.5% had a vascular injury
      (70.1% arterial), and a total of 99 limb operations were performed, including 15
      amputations. Fourteen amputations (93.3%) occurred at the scene or were directly
      attributed to the extent of tissue damage with a median Mangled Extremity
      Severity Score (MESS) of 7 (interquartile range, 2). In the remaining patient,
      the tourniquet was lifesaving but likely contributed to limb loss. Seven patients
      sustained 13 other complications; however, none was directly attributed to
      tourniquet use. CONCLUSION: Tourniquet use in the civilian sector is associated
      with a low rate of complications. With the low complication rate and high
      potential for benefit, aggressive use of this potentially lifesaving intervention
      is justified. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.

PMID- 26218694
TI  - Effects of rapid wound sealing on survival and blood loss in a swine model of
      lethal junctional arterial hemorrhage.
AB  - BACKGROUND: Hemostatic gauzes, which must be packed into wounds and compressed
      for several minutes, may be of limited use for noncompressible wounds in
      junctional anatomic locations. Rapid mechanical wound sealing is an alternative
      approach that seals the wound at the skin, allowing internal clot formation. We
      evaluate wound sealing for junctional hemorrhage control using a hemostatic clamp
      (iTClamp). METHODS: Severe junctional hemorrhage was induced in anesthetized
      immature female swine using a 5-mm femoral arteriotomy. After 30 seconds of free
      bleeding, animals were randomized to one of seven hemostatic interventions: no
      intervention (control), direct compression for 3 minutes (compression), plain
      gauze packing (packing), mechanical wound seal (seal), plain gauze packing +
      wound seal (packing + seal), plain gauze packing + compression (packing +
      compression), or hemostatic gauze packing (Combat Gauze) + compression (HS
      packing + compression). All animals then received one 15-mL/kg bolus of Hextend,
      followed by lactated Ringer's solution for hypotension up to 100 mL/kg. Animals
      were monitored for 3 hours. RESULTS: Survival was similar between control (3-hour
      survival, 0%) and compression (0%, Kaplan-Meier survival analysis and log-rank
      test [KM-LR], p = 1.0) but marginally improved with packing (12.5%, KM-LR, p <
      0.001). Survival improved with seal (62.5%) versus control (KM-LR, p < 0.001) and
      with packing + seal (100%) versus packing alone (KM-LR, p < 0.001). Survival was
      similar between packing + compression (87.5%), HS-packing + compression (62.5%),
      and packing + seal (100%) (KM-LR, p >= 0.05). Total hemorrhage volume was
      decreased for seal versus control (p < 0.001) and for packing + seal versus
      packing (p < 0.001). Hemorrhage was similar among packing + compression, HS
      packing + compression, seal, and packing + seal (analysis of variance p >= 0.05).
      Application times (mean [SD]) were significantly faster with packing + seal
      (125.8 [56.2] seconds) than packing + compression (236.6 [7.2] seconds) and HS
      packing + compression (223.0 [6.8] seconds) (analysis of variance, all p <
      0.001). CONCLUSION: In this preclinical junctional hemorrhage model, rapid wound
      sealing improved survival and decreased hemorrhage in both packed and unpacked
      wounds and performed comparably with standard-of-care hemostatic bandages.
      Rapidly sealing junctional wounds may be a viable alternative to wound
      compression.

PMID- 26218695
TI  - Measuring trauma system performance: Right patient, right place-Mission
      accomplished?
AB  - BACKGROUND: A regional trauma system must establish and monitor acceptable
      overtriage and undertriage rates. Although diagnoses from discharge data sets can
      be used with mortality prediction models to define high-risk injury,
      retrospective analyses introduce methodological errors when evaluating real-time
      triage processes. The purpose of this study was to determine if major trauma
      patients identified using field criteria correlated with those retrospectively
      labeled high risk and to assess system performance by measuring triage accuracy
      and trauma center utilization. METHODS: A statewide database was queried for all
      injury-related International Classification of Diseases, 9th Revision, code
      discharges from designated trauma centers and nontrauma centers for 2012.
      Children and burn patients were excluded. Patients assigned a trauma alert fee
      were considered field-triage(+). The International Classification Injury Severity
      Score methodology was used to estimate injury-related survival probabilities,
      with an International Classification Injury Severity Score less than 0.85
      considered high risk. Triage rates were expressed relative to the total
      population; the proportion of low- and high-risk patients discharged from trauma
      centers defined trauma center utilization. RESULTS: There were 116,990 patients
      who met study criteria, including 11,368 (10%) high-risk, 70,741 field-triage(-)
      patients treated in nontrauma centers and 28,548 field-triage(-) and 17,791 field
      triage(+) patients treated in trauma centers. Field triage was 86% accurate, with
      10% overtriage and 4% undertriage. System triage was 66% accurate, with 32%
      overtriage and 2% undertriage. Overtriage patients more often, and undertriage
      patients less often, had severe injury characteristics than appropriately triaged
      patients. CONCLUSION: Trauma system performance assessed using retrospective
      administrative data provides a convenient measure of performance but must be used
      with caution. Residual mistriage can partly be attributed to error introduced by
      retrospective high-risk definitions, whereas differences between field and system
      triage accuracy can be attributed to the trauma center's role as a large
      community hospital. Given the limitations of the data and methods, these results
      may represent optimal patient distribution within this mature system.

PMID- 26218699
TI  - Stress-induced hyperglycemia is associated with higher mortality in severe
      traumatic brain injury.
AB  - BACKGROUND: An association between stress-induced hyperglycemia (SIH) and
      increased mortality has been demonstrated following trauma. Experimental animal
      model data regarding the association between hyperglycemia and outcomes following
      traumatic brain injury (TBI) are inconsistent, suggesting that hyperglycemia may
      be harmful, neutral, or beneficial. The purpose of this study was to examine the
      effects of SIH versus diabetic hyperglycemia (DH) on severe TBI. METHODS:
      Admission glycosylated hemoglobin (HbA1c), glucose levels, and comorbidity data
      were collected during a 4-year period from September 2009 to December 2013 for
      patients with severe TBI (i.e., admission Glasgow Coma Scale [GCS] score of 3-8
      and head Abbreviated Injury Scale [AIS] score >= 3). Diabetes mellitus was
      determined by patient history or admission HbA1c of 6.5% or greater. SIH was
      determined by the absence of diabetes mellitus and admission glucose of 200 mg/dL
      or greater. A Cox proportional hazards model adjusted for age, sex, injury
      mechanism, and Injury Severity Score (ISS) was used to calculate hazard ratios
      (HRs) and associated 95% confidence intervals (CIs) for the association between
      SIH and the outcomes of interest. RESULTS: During the study period, a total of
      626 patients were included in the study group, having severe TBI defined by both
      GCS score of 3 to 8 and head AIS score being 3 or greater and also had available
      HbA1c and admission glucose levels. A total of 184 patients were admitted with
      hyperglycemia; 152 patients (82.6%) were diagnosed with SIH, and 32 patients
      (17.4%) were diagnosed with DH. When comparing patients with severe TBI adjusted
      for age, sex, injury mechanism, ISS, Revised Trauma Score (RTS), and lactic acid
      greater than 2.5 mmol/L, patients with SIH had a 50% increased mortality (HR,
      1.49; 95% CI, 1.13-1.95) compared with the nondiabetic normoglycemia patients. DH
      patients did not have a significant increase in mortality (HR, 0.94; 95% CI, 0.56
      1.58). CONCLUSION: SIH is associated with higher mortality after severe TBI. This
      association was not observed among patients with DH, which suggests that
      hyperglycemia related to diabetes is of less importance compared with SIH in
      terms of mortality in the acute trauma and TBI patient. Further research is
      warranted to identify mechanisms causing SIH and subsequent worse outcomes after
      TBI. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, leve III.

PMID- 26218697
TI  - Development of a trauma-specific quality-of-life measurement.
AB  - BACKGROUND: Complex, disease-specific factors help to determine posttraumatic
      quality of life (QoL), but current practice uses outcome measures generated from
      the general population. Trauma survivorship has grown rapidly, while defining the
      factors that influence posttraumatic QoL has lagged. This study sought to develop
      a valid and reliable trauma-specific QoL measure to help guide future
      posttraumatic research and clinical care. METHODS: Qualitative data were
      collected from adult trauma patients and their caregivers (Phase 1). Subsequent
      analysis of these data resulted in the development of a 59-item QoL
      questionnaire. The 59-item trauma-specific QoL (T-QoL) questionnaire was then
      administered to adult trauma patients (n = 394), and a factor analysis was
      conducted. The validity of the final T-QoL measurement tool was assessed (n =
      111) using the Medical Outcomes Study 36-Item Short Form Health Survey version 2
      (SF-36v2) and the PTSD Checklist-Civilian Version (PCL-C) (Phase 2). RESULTS: A
      five-component structure using 43 items seemed to best represent the data. The
      five components included emotional well-being, functional engagement,
      recovery/resilience, peritraumatic experience, and physical well-being. Four of
      the five components were found to have strong Cronbach's alpha scores (>0.7),
      demonstrating consistent interitem reliability. All subscales of the T-QoL
      correlated negatively with the PCL-C (p < 0.01), demonstrating that as the T-QoL
      increases, the likelihood of PTSD decreases. The physical well-being subscale of
      the T-QoL correlated significantly with the SF-36v2 physical component score, as
      did the emotional well-being subscale with the SF-36v2 mental component score (p
      < 0.05). CONCLUSION: This study used the experiences of trauma victims and their
      informal caregivers to develop a five-component, 43-item questionnaire with
      domains that are unique to trauma populations. Its accuracy and validity were
      confirmed using the PCL-C and the SF-36v2. We believe that the T-QoL represents a
      novel tool that can be used by trauma professionals to positively impact research
      efforts and clinical care. LEVEL OF EVIDENCE: Prognostic study, level II.

PMID- 26218698
TI  - The impact of acute care surgery on appendicitis outcomes: Results from a
      national sample of university-affiliated hospitals.
AB  - BACKGROUND: Acute appendicitis is the most common indication for emergency
      general surgery (EGS) in the United States. We examined the role of acute care
      surgery (ACS) on interventions and outcomes for acute appendicitis at a national
      sample of university-affiliated hospitals. METHODS: We surveyed senior surgeons
      responsible for EGS coverage at University HealthSystems Consortium hospitals,
      representing more than 90% of university-affiliated hospitals in the United
      States. The survey elicited data on resources allocated for EGS during 2013.
      Responses were linked to University HealthSystems Consortium outcomes data by
      unique hospital identifiers. Patients treated at hospitals reporting hybrid
      models for EGS coverage were excluded. Differences in interventions and outcomes
      between patients with acute appendicitis treated at ACS hospitals versus
      hospitals with a general surgeon on-call model (GSOC) were analyzed using
      univariate comparisons and multivariable logistic regression models adjusted for
      patient demographics, clinical acuity, and hospital characteristics. RESULTS: We
      found 122 hospitals meeting criteria for analysis where 2,565 patients were
      treated for acute appendicitis. Forty-eight percent of hospitals had an ACS model
      (n = 1,414), and 52% had a GSOC model (n = 1,151). Hospitals with ACS models were
      more likely to treat minority patients than those with GSOC models. Patients
      treated at ACS hospitals were more likely to undergo laparoscopic appendectomy.
      In multivariable modeling of patients who had surgery (n = 2,258), patients
      treated at ACS hospitals had 1.86 (95% confidence interval, 1.23-2.80) greater
      odds of undergoing laparoscopic appendectomy. CONCLUSION: In an era when
      laparoscopic appendectomy is increasingly accepted for treating uncomplicated
      acute appendicitis, particularly in low-risk patients, it is concerning that
      patients treated at GSOC model hospitals are more likely to undergo traditional
      open surgery at the time of presentation. Furthermore, hospitals with ACS are
      functioning as safety-net hospitals for vulnerable patients with acute
      appendicitis. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 26218709
TI  - Editorial overview: Chemical biotechnology: Interdisciplinary concepts for modern
      biotechnological production of biochemicals and biofuels.

PMID- 26218702
TI  - Delayed intracranial hemorrhage in the anticoagulated patient: A systematic
      review.
AB  - BACKGROUND: A significant population of elderly Americans on warfarin is at risk
      for immediate and delayed intracranial hemorrhage. This qualitative systematic
      review ascertains the delayed intracranial hemorrhage risk associated with minor
      head injury and preinjury warfarin use. METHODS: A systematic review using
      MEDLINE, EMBASE, and the Cochrane Library was performed in August 2014. Cohort
      studies evaluating delayed intracranial hemorrhage in patients with minor head
      injuries on warfarin were eligible for inclusion. The definition of delayed
      hemorrhage was any intracranial bleeding detected subsequent to initial negative
      brain imaging result following the head injury. Three authors screened and
      abstracted the data and evaluated methodological quality. Data abstraction also
      included clinical characteristics that could identify risk factors for delayed
      intracranial hemorrhage. RESULTS: The search retrieved 294 unique articles, of
      which 5 studies constituted the final review. The studies included data on 1,257
      patients. Among higher-quality studies, the incidence of delayed intracranial
      hemorrhage ranged from 5.8 to 72 per 1,000 cases of patients on warfarin with
      minor head injury. Population age was an influential factor in this range of
      incident rates. International normalized ratio levels had no clear association
      with individual risk for delayed intracranial hemorrhage. CONCLUSION: The
      incidence of delayed intracranial hemorrhage is low among patients on warfarin
      with minor head injury. Trauma centers should consider the characteristics of the
      population they serve compared with the published studies when determining
      management strategies for these patients. LEVEL OF EVIDENCE: Systematic review,
      level III.

PMID- 26218700
TI  - Impaired coagulation is a risk factor for clinical and radiologic deterioration
      in patients with traumatic brain injury and isolated traumatic subarachnoid
      hemorrhage.
AB  - BACKGROUND: Isolated traumatic subarachnoid hemorrhage (itSAH) is found in
      approximately 25% of all patients with mild traumatic brain injury (TBI). The aim
      of this study was to analyze the clinical course and identify risk factors for
      potential clinical and radiologic deterioration in consideration of impaired
      coagulation in patients with itSAH. METHODS: A retrospective analysis of 735
      patients with TBI resulting in a pathologic computer-assisted tomography (CAT)
      was performed. Only those patients with itSAH and Glasgow Coma Scale (GCS) of
      greater than 8 points and follow-up CAT scan were included. Patients with
      hemorrhage in any other brain compartment (subdural, epidural, and intracerebral)
      were excluded. Impaired coagulation was operationally defined. RESULTS: Of the
      735 patients, 89 met the inclusion criteria. The majority of these patients
      experienced mild TBI. The rate of radiologic expansion or conversion of the SAH
      was 28.1%. The rate of clinical deterioration was 6.7%. Neither the initial
      pattern of itSAH on different intracranial localizations nor the number of sulci
      involved in the itSAH was associated with clinical worsening. The rate of
      patients with impaired coagulation was 38%; 17.9% of all patients showed elevated
      international normalized ratio (INR). Radiologic and clinical deterioration was
      significantly associated with elevated INR. INR was shown to be independent of
      age in a logistic regression analysis. CONCLUSION: TBI patients with itSAH and
      impaired coagulation especially those who showed elevated INR are at risk of
      clinical and radiologic deterioration. Despite coagulation status, routine
      repetition of cranial CAT scan is advised in patients with itSAH to detect
      potential radiologic worsening, which if occurring should result in close
      clinical monitoring. LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic
      study, level III.

PMID- 26218704
TI  - Implementing and preserving the advances in combat casualty care from Iraq and
      Afghanistan throughout the US Military.
AB  - Thirteen years of continuous combat operations have enabled the US Military and
      its coalition partners to make a number of major advances in casualty care. The
      coalition nations have developed a superb combat trauma system and achieved
      unprecedented casualty survival rates. There remains, however, a need to
      accelerate the translation of new battlefield trauma care information, training,
      and equipment to units and individuals deploying in support of combat operations.
      In addition, the US Military needs to ensure that these advances are sustained
      during peace intervals and that we continue to build upon our successes as we
      prepare for future conflicts. This article contains recommendations designed to
      accomplish those goals. For the proposed actions to benefit all branches of our
      armed services, the direction will need to come from the Office of the Secretary
      of Defense in partnership with the Joint Staff. Effective translation of military
      advances in prehospital trauma care may also increase survival for law
      enforcement officers wounded in the line of duty and for civilian victims of
      Active Shooter or terrorist-related mass-casualty incidents. 

PMID- 26218706
TI  - Re: Optimal training for emergency needle thoracostomy.

PMID- 26218705
TI  - An experimental novel alternative for temporary abdominal closure of the open
      abdomen: Transfascial continuous tension.

PMID- 26218701
TI  - Mechanisms of early trauma-induced coagulopathy: The clot thickens or not?
AB  - Traumatic-induced coagulopathy (TIC) is a hemostatic disorder that is associated
      with significant bleeding, transfusion requirements, morbidity and mortality. A
      disorder similar or analogous to TIC was reported around 70 years ago in patients
      with shock, hemorrhage, burns, cardiac arrest or undergoing major surgery, and
      the condition was referred to as a "severe bleeding tendency," "defibrination
      syndrome," "consumptive disorder," and later by surgeons treating US Vietnam
      combat casualties as a "diffuse oozing coagulopathy." In 1982, Moore's group
      termed it the "bloody vicious cycle," others "the lethal triad," and in 2003
      Brohi and colleagues introduced "acute traumatic coagulopathy" (ATC). Since that
      time, early TIC has been cloaked in many names and acronyms, including a
      "fibrinolytic form of disseminated intravascular coagulopathy (DIC)." A global
      consensus on naming is urgently required to avoid confusion. In our view, TIC is
      a dynamic entity that evolves over time and no single hypothesis adequately
      explains the different manifestations of the coagulopathy. However, early TIC is
      not DIC because an increased thrombin-generating potential in vitro does not
      imply a clinically relevant thrombotic state in vivo as early TIC is
      characterized by excessive bleeding, not thrombosis. DIC with its diffuse
      anatomopathologic fibrin deposition appears to be a latter phase progression of
      TIC associated with unchecked inflammation and multiple organ dysfunction. 

PMID- 26218703
TI  - Conflict management teams in the intensive care unit: A concise definitive
      review.

PMID- 26218712
TI  - Biophysical characterization of the interaction between human serum albumin and n
      dodecyl beta-D-maltoside: A multi-technique approach.
AB  - We have studied the effect of biocompatible sugar based surfactant n-dodecyl beta
      D-maltoside (DDM) on the conformation of human serum albumin (HSA). A multi
      technique approach was applied in order to understand the type of interaction and
      effect of DDM on the secondary and tertiary structure of HSA. Surface tension
      measurement showed that HSA shifted the critical micelle concentration (cmc) of
      the surfactant to the higher side that clarifies the complex formation between
      DDM and HSA which was also confirmed by UV absorption spectroscopy. Fluorescence
      quenching measurements showed that fluorescence of HSA was quenched by the
      addition of DDM with a prominent blue shift indicative of the involvement of
      hydrophobic interaction which was further confirmed by extrinsic fluorescence of
      organic dye 1-anilino-8-naphthalenesulfonate. Synchronous fluorescence
      measurement trends suggested that the hydrophobicity increases near the
      tryptophan residue while an increase in the polarity was observed near tyrosine
      residues. A collective information obtained by circular dicroism (CD) and Fourier
      transform infra-red (FTIR) spectroscopies along with dynamic light scattering
      revealed the partial unfolding of the protein.

PMID- 26218710
TI  - Differential gene expression in Xylella fastidiosa 9a5c during co-cultivation
      with the endophytic bacterium Methylobacterium mesophilicum SR1.6/6.
AB  - Xylella fastidiosa, the causal agent of citrus variegated chlorosis (CVC),
      colonizes plant xylem, reducing sap flow, and inducing internerval chlorosis,
      leaf size reduction, necrosis, and harder and smaller fruits. This bacterium may
      be transmitted from plant to plant by sharpshooter insects, including
      Bucephalogonia xanthopis. The citrus endophytic bacterium Methylobacterium
      mesophilicum SR1.6/6 colonizes citrus xylem and previous studies showed that this
      strain is also transferred from plant to plant by B. xanthopis (Insecta),
      suggesting that this endophytic bacterium may interact with X. fastidiosa in
      planta and inside the insect vector during co-transmission by the same insect
      vector. To better understand the X. fastidiosa behavior in the presence of M.
      mesophilicum, we evaluated the X. fastidiosa transcriptional profile during in
      vitro interaction with M. mesophilicum SR1.6/6. The results showed that during co
      cultivation, X. fastidiosa down-regulated genes related to growth and up
      regulated genes related to energy production, stress, transport, and motility,
      suggesting the existence of a specific adaptive response to the presence of M.
      mesophilicum in the culture medium. 

PMID- 26218720
TI  - Mechanistic Understanding of the Divergent Reactivity of Cyclopropenes in Rh(III)
      Catalyzed C-H Activation/Cycloaddition Reactions of N-Phenoxyacetamide and N
      Pivaloxybenzamide.
AB  - Density functional theory calculations were conducted to develop a mechanistic
      understanding of the Rh(III)-catalyzed C-H activation/cycloaddition reactions of
      N-phenoxyacetamide and N-pivaloxybenzamide with cyclopropenes, and insights into
      the substrate-dependent chemoselectivity were provided. The results showed that
      the divergence originated from the different reactivity of the seven-membered
      rhodacycles from the insertion of cyclopropene into the Rh-C bond. In reactions
      of N-pivaloxybenzamide, such an intermediate undergoes the pivalate migration to
      form a cyclic Rh(V)-nitrenoid intermediate in a reaction that is easier than the
      opening of the three-membered ring by beta-carbon elimination, leading finally to
      a tricyclic product with retention of the cyclopropane moiety by facile reductive
      elimination. While similar Rh(V)-nitrenoid species could also be possibly formed
      in Cp*Rh(III)-catalyzed reactions of N-phenoxyacetamide, the beta-carbon
      elimination occurs more easily from the corresponding seven-membered rhodacycle
      intermediate and the subsequent O-N bond cleavage gives rise to an unexpected
      dearomatized (E)-6-alkenylcyclohexa-2,4-dienone intermediate. The E/Z
      isomerization of this intermediate is required for the final cyclization to 2H
      chromene, and interesting metal-ligand cooperative catalysis with Rh(III)
      carboxylate was disclosed in the C?C double bond rotation process. 

PMID- 26218716
TI  - Toward Understanding the Decomposition of Carbonyl Diazide (N3)2C?O and Formation
      of Diazirinone cycl-N2CO: Experiment and Computations.
AB  - Carbonyl diazide, (N3)2CO (I), is a highly explosive compound. The isolation of
      the substance in a neat form was found to provide unique access to two other high
      energy molecules, namely, N3-NCO (III) and cycl-N2CO (IV), among the
      decomposition products of (I). To understand the underlying reaction mechanism,
      the decomposition reactions including the thermal conversion of two conformers of
      (I) were revisited, and the potential energy surface (PES) was computationally
      explored by using the methods of B3LYP/6-311+G(3df) and CBS-QB3. The most stable
      syn-syn structure (I) readily converts into the syn-anti conformer (DeltaHexptl =
      1.1 +/- 0.5 kcal mol(-1)), which undergoes decomposition in two competing
      pathways: a concerted path to N3-NCO (III) or a stepwise route to (III) via the
      nitrene intermediate N3C(O)N (1)(II). The calculated activation barriers (Ea) are
      almost the same (~33 kcal mol(-1), B3LYP/6-311+G(3df)). Further decomposition of
      (III) occurs through a concerted fragmentation into 2 N2 + CO with a moderate Ea
      of 22 kcal mol(-1), and this process is compared to the isoelectronic species N3
      N3 -> 3 N2 (Ea = 17 kcal mol(-1)) and OCN-NCO -> N2 + 2 CO (61 kcal mol(-1)). No
      low-energy pathway leading to (IV) was found on the singlet PES. However, the
      intervention of triplet ground-state (3)(II) from the initially generated (1)(II)
      through an intersystem crossing (ISC) offers a likely approach to (IV); that is,
      (3)(II) can decompose in a concerted process (Ea = 30 kcal mol(-1)) by
      eliminating one N2 to yield the disfavored OCNN (3)(VI). A careful intrinsic
      reaction coordinate analysis and a combined energy scan of the N-C-N angle
      reveals a bifurcation point on this triplet PES, which allows a spin crossover to
      the singlet PES along the reaction coordinate and eventually leads to the
      formation of the metastable diazirinone (IV). 

PMID- 26218715
TI  - Glucagon-like peptide-2-loaded microspheres as treatment for ulcerative colitis
      in the murine model.
AB  - Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that promotes intestinal
      growth, but the rapid degradation by dipeptidyl peptidase-IV limits its
      applications. PLGA microsphere is a well-developed drug delivery system, while
      seldom been studied as a solution for prolonging in vivo effects of GLP-2. In
      this study, we encapsulated porcine GLP-2 (pGLP-2) into microspheres and
      investigated its therapeutic effects in dextran sulfate sodium (DSS)-treated
      mice. pGLP-2 microspheres showed 20.36% in initial burst and constant release for
      at least 9 d. In the DSS-treated mice, a single injection of GLP-2 microspheres
      significantly increased the body weight, colonic length, small intestinal weight
      and mRNA expression of Occludin, decreased the colonic damage score, mRNA
      expression of IL-6, IL-10, TNF-alpha and IFN-gamma. In conclusion, pGLP-2
      microspheres were resistant to degradation and decreased the severity of DSS
      induced ulcerative colitis which suggested that GLP-2-loaded microspheres could
      be a proper candidate for the treatment of ulcerative colitis. 

PMID- 26218714
TI  - Detection and Characterization of Antimicrobial Resistance and Putative Virulence
      Genes in Aeromonas veronii Biovar Sobria Isolated from Gilthead Sea Bream (Sparus
      aurata L.).
AB  - The purposes of this study were to investigate the antimicrobial resistance of
      Aeromonas veronii biovar sobria isolated from gilthead sea bream and to
      characterize the virulence-implicated genes. Fish samples (n=365) were collected
      from wholesale and retail markets in Aljouf, Saudi Arabia between 2013 and 2014.
      A total of 45 A. veronii biovar sobria isolates (12.3%) from those samples were
      tested for resistance to a range of antimicrobial agents. All strains exhibited
      100% resistances to nalidixic acid, carbenicillin, cephalothin, erythromycin,
      kanamycin, tetracycline, and trimethoprim-sulfamethoxazole. Additionally, the
      highest susceptibility encountered was to ciprofloxacin (100%). In the present
      study, we examined the presence of several genes, including aerolysin, elastase,
      lipase, flagellin, enterotoxin, and DNases, that code for putative virulence
      factors that may play important roles in bacterial infection. It was found that
      all of these genes were common in these strains. Several strains isolated from
      diseased gilthead sea bream were tested for virulence in gilthead sea bream by
      intraperitoneal injections. The median lethal dose values ranged from 5*10(3) to
      5.2*10(9) colony-forming units per fish. These data suggest that commercial
      gilthead sea bream fish may act as the reservoir for multiresistant A. veronii
      biovar sobria and facilitate the dissemination of virulence genes. 

PMID- 26218722
TI  - How to review a manuscript.
AB  - BACKGROUND: Peer review of submitted manuscripts is widely perceived as a
      cornerstone of assuring quality in academic journals. However, in medical school
      and beyond, dermatologic surgeons receive minimal instruction in the methodology
      of critically reviewing new literature. OBJECTIVE: To guide new or less
      experienced reviewers through the steps of assessing a manuscript for the
      journal. To clarify the most important elements of the review and to discuss
      common pitfalls and their avoidance. METHODS: A stepwise template was suggested
      on how to review manuscripts. RESULTS: An algorithmic approach to reviewing a
      paper can demystify the process, increase efficiency, and reduce the likelihood
      that important elements of the review will be omitted or overlooked. Nonetheless,
      this recommended approach is a starting point, and individual reviewers would be
      expected to modify it to reflect their particular preferences and to adapt it to
      specific papers. CONCLUSION: Reviewing a manuscript for the journal is amenable
      to a simple algorithmic approach. Encouraging recent graduates and others to
      review for the journal by clarifying the process can further assist the editorial
      staff in selecting the best manuscripts and improving these before publication.

PMID- 26218717
TI  - Inhibitor Fingerprinting of Rhomboid Proteases by Activity-Based Protein
      Profiling Reveals Inhibitor Selectivity and Rhomboid Autoprocessing.
AB  - Rhomboid proteases were discovered almost 15 years ago and are structurally the
      best characterized intramembrane proteases. Apart from the general serine
      protease inhibitor 3,4-dichloro-isocoumarin (DCI) and a few crystal structures of
      the Escherichia coli rhomboid GlpG with other inhibitors, there is surprisingly
      little information about inhibitors of rhomboids from other species, probably
      because of a lack of general methods to measure inhibition against different
      rhomboid species. We here present activity-based protein profiling (ABPP) as a
      general method to screen rhomboids for their activity and inhibition. Using ABPP,
      we compare the inhibitory capacity of 50 small molecules against 13 different
      rhomboids. We find one new pan rhomboid inhibitor and several inhibitors that
      display selectivity. We also demonstrate that inhibition profile and sequence
      similarity of rhomboids are not related, which suggests that related rhomboids
      may be selectively inhibited. Finally, by making use of the here discovered
      inhibitors, we were able to show that two bacterial rhomboids autoprocess
      themselves in their N-terminal part. 

PMID- 26218711
TI  - Performance metrics for evaluating system suitability in liquid chromatography-
      Mass spectrometry peptide mass mapping of protein therapeutics and monoclonal
      antibodies.
AB  - The use of liquid chromatography--mass spectrometry (LC-MS) for the
      characterization of proteins can provide a plethora of information related to
      their structure, including amino acid sequence determination and analysis of
      posttranslational modifications. The variety of LC-MS based applications has led
      to the use of LC-MS characterization of therapeutic proteins and monoclonal
      antibodies as an integral part of the regulatory approval process. However, the
      improper use of an LC-MS system, related to intrinsic instrument limitations,
      improper tuning parameters, or poorly optimized methods may result in the
      production of low quality data. Improper system performance may arise from subtle
      changes in operating conditions that limit the ability to detect low abundance
      species. To address this issue, we systematically evaluated LC-MS/MS operating
      parameters to identify a set of metrics that can be used in a workflow to
      determine if a system is suitable for its intended purpose. Development of this
      workflow utilized a bovine serum albumin (BSA) digest standard spiked with
      synthetic peptides present at 0.1% to 100% of the BSA digest peptide
      concentration to simulate the detection of low abundance species using a
      traditional bottom-up workflow and data-dependent MS(2) acquisition. BSA sequence
      coverage, a commonly used indicator for instrument performance did not
      effectively identify settings that led to limited dynamic range or poorer
      absolute mass accuracy on 2 separate LC-MS systems. Additional metrics focusing
      on the detection limit and sensitivity for peptide identification were determined
      to be necessary to establish system suitability for protein therapeutic
      characterization by LC-MS.

PMID- 26218724
TI  - Retention of Mohs surgeons in academic dermatology.
AB  - BACKGROUND: Retention of academic Mohs surgeons is important for the growth of
      this specialty and teaching of residents and students. OBJECTIVE: To examine
      factors that influence retention of Mohs surgeons in academics and to better
      understand reasons for their departure. MATERIALS AND METHODS: A survey was
      electronically distributed to academic Mohs surgeons in the American College of
      Mohs Surgery, asking them to rate the importance of several variables on their
      decision to remain in academia. Private practice Mohs surgeons who had left
      academics were also surveyed. RESULTS: Two hundred thirty-six dermatologic
      surgeons completed the survey. Twenty-nine percent work full time in academics,
      and approximately 7% work part time. The top reasons for practicing in the
      academic setting are intellectual stimulation, teaching opportunities, and
      collaboration with other university physicians and researchers. Seventy-one
      percent of respondents reported they would stay in academics, 7% indicated they
      would not, and 22% were unsure. Unfair compensation, inadequate support staff,
      poor leadership, increased bureaucracy, and decreased autonomy were top reasons
      that may compel a Mohs surgeon to leave. CONCLUSION: Opportunities for
      intellectual stimulation, collaboration, and teaching remain the main draw for
      academic Mohs surgeons. A supportive environment, strong leadership, and
      establishing fair compensation are imperative in ensuring their stay.

PMID- 26218718
TI  - Monitoring Disease Progression and Therapeutic Response in a Disseminated Tumor
      Model for Non-Hodgkin Lymphoma by Bioluminescence Imaging.
AB  - Xenograft tumor models are widely studied in cancer research. Our aim was to
      establish and apply a model for aggressive CD20-positive B-cell non-Hodgkin
      lymphomas, enabling us to monitor tumor growth and shrinkage in a noninvasive
      manner. By stably transfecting a luciferase expression vector, we created two
      bioluminescent human non-Hodgkin lymphoma cell lines, Jeko1(luci) and OCI
      Ly3(luci), that are CD20 positive, a prerequisite to studying rituximab, a
      chimeric anti-CD20 antibody. To investigate the therapy response in vivo, we
      established a disseminated xenograft tumor model injecting these cell lines in
      NOD/SCID mice. We observed a close correlation of bioluminescence intensity and
      tumor burden, allowing us to monitor therapy response in the living animal.
      Cyclophosphamide reduced tumor burden in mice injected with either cell line in a
      dose-dependent manner. Rituximab alone was effective in OCI-Ly3(luci)-injected
      mice and acted additively in combination with cyclophosphamide. In contrast, it
      improved the therapeutic outcome of Jeko1(luci)-injected mice only in combination
      with cyclophosphamide. We conclude that well-established bioluminescence imaging
      is a valuable tool in disseminated xenograft tumor models. Our model can be
      translated to other cell lines and used to examine new therapeutic agents and
      schedules.

PMID- 26218723
TI  - Polypodium leucotomos supplementation in the treatment of scalp actinic
      keratosis: could it improve the efficacy of photodynamic therapy?
AB  - BACKGROUND: Actinic keratoses (AKs) are a common premalignant skin condition.
      Many treatments are available for AKs. Photodynamic therapy (PDT) is one of the
      most effective treatments. However, major concerns exist on the possibility of
      PDT-induced DNA-mutagenesis/immunosuppression, leading to AKs
      recurrence/treatment failure. An extract (PLE) from the fern polypodium
      leucotomos reduces UV-induced immunosuppression and mutagenesis. OBJECTIVE: To
      assess the ability of PLE to enhance the efficacy of PDT treatment, reducing AKs
      recurrence on the scalp. MATERIALS AND METHODS: Thirty-four bald patients
      presenting at least two AKs on the scalp were alternatively assigned to two
      groups. Both groups underwent two PDT-sessions one-week apart. The first group
      began oral PLE supplementation one week after the last PDT session. Evaluation of
      the effect of PLE supplementation was performed by direct inspection of the bald
      areas, lesions count, and photodynamic diagnosis assessment at 2 and 6 months.
      RESULTS: Both groups were homogeneous in terms of skin phototype and previous UV
      exposure. Mean age was 75.7 +/- 7.8 years and 76.5 +/- 5.5 years, respectively.
      Both treatment modalities were successful in reducing AKs number (p < .001).
      However, PLE supplementation increased clearance rate compared with PDT alone (p
      = .040). CONCLUSION: Polypodium leucotomos improves PDT clearance and decreases
      AK recurrence rate at 6 months, suggesting its use as a complementary agent in
      the treatment of field cancerization.

PMID- 26218729
TI  - Comparison of onabotulinumtoxinA and rimabotulinumtoxinB for the treatment of
      axillary hyperhidrosis.
AB  - BACKGROUND: Recently, rimabotulinumtoxinB has been increasingly used as an off
      label treatment of primary axillary hyperhidrosis (PAH). However, the optimal
      conversion ratios for onabotulinumtoxinA and rimabotulinumtoxinB remain to be
      determined. OBJECTIVE: To compare effectiveness, satisfaction level, and safety
      of rimabotulinumtoxinB with onabotulinumtoxinA at a conversion ratio of 1:30 for
      the treatment of PAH. METHODS: Adults with PAH were enrolled in this bilaterally
      paired single-subject study. Each patient was randomly treated with 1,500 U
      rimabotulinumtoxinB on 1 axilla and 50 U onabotulinumtoxinA contralaterally.
      Hyperhidrosis Disease Severity Scale was assessed before and after treatment up
      to 20 weeks. A 10-cm visual analog scale representing improvement of hidrotic
      symptom and starch-iodine test were also used to assess therapeutic efficacy.
      RESULTS: Twenty-four patients completed the study. Both groups showed comparable
      and efficacious anhidrotic effects through 20 weeks for any variable. There were
      no significant differences in terms of the onset of action or mean duration of
      action between the 2 groups. Overall satisfaction with the treatment was equally
      high in both groups. CONCLUSION: Both toxins showed comparable anhidrotic effect
      for the treatment of axillary hyperhidrosis at a conversion ratio of 1:30.

PMID- 26218728
TI  - Subject satisfaction with onabotulinumtoxinA treatment of glabellar and lateral
      canthal lines using a new patient-reported outcome measure.
AB  - BACKGROUND: Patient satisfaction with treatment is an important outcome in facial
      aesthetic medicine. OBJECTIVE: To evaluate subject satisfaction with
      onabotulinumtoxinA treatment of glabellar lines (GL) and crow's feet lines (CFL)
      using the validated Facial Line Satisfaction Questionnaire (FLSQ). METHODS: In
      this randomized double-blind study, subjects with moderate/severe GL and CFL
      received onabotulinumtoxinA (20 U, GL; 24 U, CFL) or placebo. Over 120 days, the
      following were assessed: satisfaction, achievement of treatment expectations,
      satisfaction with duration of treatment (FLSQ), severity of GL and CFL (Facial
      Wrinkle Scale [FWS]), and aesthetic improvement (Global Aesthetic Improvement
      Scale). RESULTS: Satisfaction in the per-protocol population was significantly
      greater at Day 60 in the onabotulinumtoxinA group (n = 60) compared with placebo
      (n = 57) for GL (81.7% vs 0%; p < .001). Most subjects treated with
      onabotulinumtoxinA remained satisfied up to 120 days. Achievement of treatment
      expectations (86.7%; Day 60), satisfaction (81.7%; Day 60), and satisfaction with
      the duration of treatment (61.6%; Day 90) were significantly better with
      onabotulinumtoxinA than placebo (p < .001) for GL and CFL combined. Efficacy
      (FWS) and aesthetic improvement were observed in most subjects at Days 30 and 60,
      respectively. CONCLUSION: High satisfaction rates are achieved and sustained in
      subjects treated with onabotulinumtoxinA for GL and CFL combined.

PMID- 26218730
TI  - Reconstruction of defects of the posterior pinna.

PMID- 26218713
TI  - Preparation of chitosan/nano hydroxyapatite organic-inorganic hybrid microspheres
      for bone repair.
AB  - In this work, we encapsulated icariin (ICA) into chitosan (CS)/nano
      hydroxyapatite (nHAP) composite microspheres to form organic-inorganic hybrid
      microspheres for drug delivery carrier. The composition and morphology of
      composite microspheres were characterized by X-ray diffraction (XRD), Fourier
      transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and
      differential scanning calorimetry- thermogravimetric analysis (DSC-TGA).
      Moreover, we further studied the performance of swelling properties, degradation
      properties and drug release behavior of the microspheres. ICA, the extract of
      traditional Chinese medicine-epimedium, was combined to study drug release
      properties of the microspheres. ICA loaded microspheres take on a sustained
      release behavior, which can be not only ascribed to electrostatic interaction
      between reactive negative hydroxyl (OH) of ICA and positive amine groups (NH2) of
      CS, but also depended on the homogeneous dispersion of HAP nanoparticles inside
      CS organic matrix. In addition, the adhesion and morphology of osteoblasts were
      detected by inverted fluorescence microscopy. The biocompatibility of CS/nHAP/ICA
      microspheres was evaluated by the MTT cytotoxicity assay, Hoechst 33258 and PI
      fluorescence staining. These studies demonstrate that composite microspheres
      provide a suitable microenvironment for osteoblast attachment and proliferation.
      It can be speculated that the ICA loaded CS-based organic-inorganic hybrid
      microspheres might have potential applications in drug delivery systems.

PMID- 26218731
TI  - A novel noninvasive wound closure device as the final layer in skin closure.

PMID- 26218726
TI  - Continuous versus interrupted sutures for facial surgery repair: a randomized
      prospective study.
AB  - BACKGROUND: The cosmetic appearance of a facial scar is a concern for patients
      undergoing Mohs micrographic surgery (MMS). Although suturing technique may
      influence scar cosmesis, few studies have been published comparing suturing
      methods for MMS repair. OBJECTIVE: To compare the cosmetic appearance of facial
      MMS scars sutured with either continuous or interrupted percutaneous nylon
      sutures. MATERIALS AND METHODS: Patients with facial MMS defects were randomized
      to have half their scar sutured with interrupted 5-0 nylon stitches, whereas the
      other half of the scar was closed with running 5-0 nylon stitches. The appearance
      of each half of the scar was assessed at 1 week, 8 weeks, and 6 months by the
      principal investigator. Blinded photographic evaluation at 1 week and 6 months
      was completed by a plastic surgeon and general dermatologist. RESULTS: A total of
      105 patients were entered into the trial, and 101 completed all time point
      assessments. There was no statistically significant difference in scar outcome
      using each of the 3 scar assessment scales, at any time point, for any assessor
      (blinded and nonblinded). CONCLUSION: Interrupted and continuous 5-0 nylon
      sutures result in an equivalent final cosmetic appearance of facial MMS scars.
      Given its advantages, running sutures may be the preferred closure technique for
      facial repair.

PMID- 26218727
TI  - Duration of effect by injection volume and facial subregion for a volumizing
      hyaluronic acid filler in treating midface volume deficit.
AB  - BACKGROUND: Juvederm Voluma XC (VYC-20L) is approved in the United States for
      correction of age-related volume loss in the midface region in adults. OBJECTIVE:
      To characterize the effects of VYC-20L in 3 midface subregions based on injection
      volumes. METHODS: In this single-blind controlled trial, subjects with midface
      volume deficit received VYC-20L in >=1 of 3 facial subregions (zygomaticomalar,
      anteromedial cheek, and submalar), with touch-up treatment available 30 days
      later. Responders achieved >=1-point improvement on the Mid-Face Volume Deficit
      Scale (MFVDS), analyzed by facial subregion and stratified by injection volume
      quartiles. Subject satisfaction and safety were assessed. RESULTS: The treatment
      arm comprised 235 subjects aged 35 to 65 years. Month 6 MFVDS responder rates
      were 75.5% for zygomaticomalar, 83.2% for anteromedial cheek, and 76.9% for
      submalar subregions. Higher responder rates were observed with increasing
      injection volume quartiles for each subregion. Similar median injection volumes
      (~2.0 mL total) of VYC-20L provided correction durations of 15 to 24 months: 24
      months for anteromedial cheek, 19 months for zygomaticomalar, and 15 months for
      submalar subregions. Subject satisfaction was high across injection volume
      quartiles. No unanticipated treatment-site adverse reactions occurred.
      CONCLUSION: VYC-20L is effective at restoring midface volume, with high subject
      satisfaction and an acceptable safety profile.

PMID- 26218719
TI  - A systematic review and meta-analysis of risk factors for postherpetic neuralgia.
AB  - Patients with herpes zoster can develop persistent pain after rash healing, a
      complication known as postherpetic neuralgia. By preventing zoster through
      vaccination, the risk of this common complication is reduced. We searched MEDLINE
      and Embase for studies assessing risk factors for postherpetic neuralgia, with a
      view to informing vaccination policy. Nineteen prospective studies were
      identified. Meta-analysis showed significant increases in the risk of
      postherpetic neuralgia with clinical features of acute zoster including prodromal
      pain (summary rate ratio 2.29, 95% confidence interval: 1.42-3.69), severe acute
      pain (2.23, 1.71-2.92), severe rash (2.63, 1.89-3.66), and ophthalmic involvement
      (2.51, 1.29-4.86). Older age was significantly associated with postherpetic
      neuralgia; for individual studies, relative risk estimates per 10-year increase
      ranged from 1.22 to 3.11. Evidence for differences by gender was conflicting,
      with considerable between-study heterogeneity. A proportion of studies reported
      an increased risk of postherpetic neuralgia with severe immunosuppression
      (studies, n = 3/5) and diabetes mellitus (n = 1/4). Systemic lupus erythematosus,
      recent trauma, and personality disorder symptoms were associated with
      postherpetic neuralgia in single studies. No evidence of higher postherpetic
      neuralgia risk was found with depression (n = 4) or cancer (n = 5). Our review
      confirms a number of clinical features of acute zoster are risk factors for
      postherpetic neuralgia. It has also identified a range of possible vaccine
      targetable risk factors for postherpetic neuralgia; yet aside from age-associated
      risks, evidence regarding risk factors to inform zoster vaccination policy is
      currently limited. 

PMID- 26218734
TI  - Noncommunicable Diseases: A Globalization of Disparity?
AB  - Peter Hotez and Larry Peiperl argue that the world's poorest people may take on a
      disproportionate burden of noncommunicable diseases, even as their home countries
      gain in economic power. 

PMID- 26218725
TI  - Laboratory errors leading to nonmelanoma skin cancer recurrence after Mohs
      micrographic surgery.
AB  - BACKGROUND: Compared with standard surgical excision, Mohs micrographic surgery
      (MMS) provides superior cure rates for nonmelanoma skin cancer (NMSC). Although
      cure rates of NMSC approach 99% with MMS, local recurrences occasionally occur.
      OBJECTIVE: The authors sought to identify histological features during frozen
      section examination that were associated with local recurrence of NMSC after MMS.
      MATERIALS AND METHODS: A retrospective chart review was performed of patients
      undergoing a second MMS procedure to treat locally recurrent NMSC over a 20-month
      period. Histological slides were reviewed to assess for possible causes of local
      recurrence. RESULTS: Of 3,169 NMSCs treated, 22 were locally recurrent. Possible
      causes of recurrence identified after MMS included dense inflammation in the
      final margin at sites affected by tumor in prior slides (27%), visible remaining
      tumor (23%), missing epidermal or dermal tissue (23%), and actinic keratosis
      (4%). One recurrence was possibly explained by incorrect mapping. No abnormality
      could be detected in 18% of cases. Possible limitations include the small sample
      size, retrospective design, and the possibility that some patients may have been
      lost to follow-up. CONCLUSION: Local recurrences after MMS are extremely rare.
      When recurrences do occur, they can be attributed to errors in histological
      interpretation or tumor mapping.

PMID- 26218735
TI  - Quantitative Genetics of the Aging of Reproductive Traits in the Houbara Bustard.
AB  - Do all traits within an organism age for the same reason? Evolutionary theories
      of aging share a common assumption: the strength of natural selection declines
      with age. A corollary is that additive genetic variance should increase with age.
      However, not all senescent traits display such increases suggesting that other
      mechanisms may be at play. Using longitudinal data collected from more than 5400
      houbara bustards (Chlamydotis undulata) with an exhaustive recorded pedigree, we
      investigated the genetics of aging in one female reproductive trait (egg
      production) and three male reproductive traits (courtship display rate, ejaculate
      size and sperm viability), that display senescence at the phenotypic level.
      Animal models revealed an increase in additive genetic variance with age for
      courtship display rate and egg production but an unexpected absence of increased
      additive genetic variance for ejaculate size and no additive genetic variance for
      sperm viability. Our results suggest that the mechanisms behind the senescence of
      some traits are linked with a change in genetic expression, whereas for some
      other traits, aging may result from the constraints associated with physiological
      wear and tear on the organism throughout the life of the individual. 

PMID- 26218732
TI  - Chemically Modified Dendritic Starch: A Novel Nanomaterial for siRNA Delivery.
AB  - Nanostructured starches are naturally derived nanomaterials that can be
      chemically modified to allow for the introduction of functional groups, enhancing
      their potential for drug delivery and other biotechnology applications. In this
      proof of concept study, we investigate chemically modified, enzymatically
      synthesized glycogen (ESG) nanodendrites as a biodegradable, biocompatible, siRNA
      delivery system. Commercially available ESG was modified using
      glycidyltrimethylammonium chloride (GTMA), introducing quaternary ammonium groups
      via an epoxide ring opening reaction. This cationic ESG (cESG) electrostatically
      bound siRNA and successfully knocked down protein expression in an in vitro
      ovarian clear cell carcinoma model. The construct exhibited sustained siRNA
      delivery for up to 6 days while exhibiting less toxicity than a common liposome
      based siRNA delivery reagent, Lipofectamine RNAiMAX. These promising results set
      the stage for the use of dendritic starch as a cost-effective, easily modifiable
      nanoscale delivery system for a diverse range of cargo including nucleic acids
      and therapeutic compounds. 

PMID- 26218741
TI  - VDR/vitamin D receptor regulates autophagic activity through ATG16L1.
AB  - The Paneth cell is a unique intestinal epithelial cell that can sense the gut
      microbiome and secrete anti-microbial peptides, thereby playing critical roles in
      the maintenance of homeostasis at the intestinal-microbial interface. These roles
      in regulating innate immunity and intestinal microbial ecology are dependent on a
      functional autophagy pathway through ATG16L1. ATG16L1 is a regulator for
      autophagy and a risk gene for inflammatory bowel disease (IBD). We demonstrated
      that a low VDR/vitamin D receptor level in the intestine is associated with
      abnormal Paneth cells, impaired autophagy function, and imbalanced bacterial
      profile (dysbiosis), accompanied by a reduction of ATG16L1. We determined that
      VDR transcriptionally regulates ATG16L1 as a VDR target gene. Administration of
      the bacterial product butyrate increases intestinal VDR expression and suppresses
      inflammation in a colitis model. Thus, our study indicates that VDR may be a
      determinant of IBD risk through its actions on ATG16L1. These insights can be
      leveraged to define therapeutic targets for restoring Paneth cells and autophagy
      through VDR in chronic inflammation. It may also have applicability for
      infectious diseases and autoimmune diseases associated with skin or lung, where
      the host is in contact with bacteria.

PMID- 26218742
TI  - A multimodal nano agent for image-guided cancer surgery.
AB  - Intraoperative imaging technologies including computed tomography and
      fluorescence optical imaging are becoming routine tools in the cancer surgery
      operating room. They constitute an enabling platform for high performance
      surgical resections that assure local control while minimizing morbidity. New
      contrast agents that can increase the sensitivity and visualization power of
      existing intraoperative imaging techniques will further enhance their clinical
      benefit. We report here the development, detection and visualization of a dual
      modality computed tomography and near-infrared fluorescence nano liposomal agent
      (CF800) in multiple preclinical animal models of cancer. We describe the
      successful application of this agent for combined preoperative computed
      tomography based three-dimensional surgical planning and intraoperative target
      mapping (>200 Hounsfield Units enhancement), as well as near-infrared
      fluorescence guided resection (>5-fold tumor-to-background ratio). These results
      strongly support the clinical advancement of this agent for image-guided surgery
      with potential to improve lesion localization, margin delineation and metastatic
      lymph node detection. 

PMID- 26218733
TI  - Temporal lobe epilepsy patients with severe hippocampal neuron loss but normal
      hippocampal volume: Extracellular matrix molecules are important for the
      maintenance of hippocampal volume.
AB  - OBJECTIVE: Hippocampal sclerosis is a common finding in patients with temporal
      lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the
      reduction of hippocampal volume with the neuron loss seen on histologic
      evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major
      component of brain extracellular matrix, are also seen in hippocampal sclerosis.
      Our aim was to evaluate the association between hippocampal volume and
      chondroitin sulfate, as well as neuronal and astroglial populations in the
      hippocampus of patients with TLE. METHODS: Patients with drug-resistant TLE were
      subdivided, according to hippocampal volume measured by MRI, into two groups:
      hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE
      patients and age-matched controls were submitted to immunohistochemistry to
      evaluate neuronal population, astroglial population, and chondroitin sulfate
      expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary
      acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively.
      RESULTS: Both TLE groups were clinically similar. NV cases had higher hippocampal
      volume, both ipsilateral and contralateral, when compared to HA. Compared to
      controls, NV and HA patients had reduced neuron density, and increased GFAP and
      CS-56 immunopositive area. There was no statistical difference between NV and HA
      groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal
      volume correlated positively with neuron density in CA1 and prosubiculum, and
      with immunopositive areas for CS-56 in CA1, and negatively with immunopositive
      area for GFAP in CA1. Multiple linear regression analysis indicated that both
      neuron density and CS-56 immunopositive area in CA1 were statistically
      significant predictors of hippocampal volume. SIGNIFICANCE: Our findings indicate
      that neuron density and chondroitin sulfate immunopositive area in the CA1
      subfield are crucial for the hippocampal volume, and that chondroitin sulfate is
      important for the maintenance of a normal hippocampal volume in some cases with
      severe neuron loss.

PMID- 26218738
TI  - Identifying clinically meaningful benchmarks for gait improvement after total hip
      arthroplasty.
AB  - There are no established benchmarks for gait mechanics after total hip
      arthroplasty (THA). This study sought to identify minimum clinically important
      postoperative (MCIP) or minimum clinically important improvement (MCII) values
      for self-selected walking speed, sagittal plane dynamic hip range of motion
      (HROM) (peak flexion-peak extension) and peak hip adduction moments measured
      during quantitative gait analysis. Preoperative and 1-year postoperative data
      collected during quantitative gait analysis, along with Harris Hip Scores (HHS),
      for 145 subjects were collected from a motion analysis data repository. The MCIP
      (or MCII) was defined as the 75th percentile mark on a plot of the cumulative
      percent of subjects with HHS >= 80 versus the postoperative value (or change) in
      the respective variable. 95% confidence intervals (CI) were calculated. Logistic
      regression was used to test the association of age, sex, BMI, and preoperative
      HHS with benchmarks. The MCIP of speed was 1.34 m/s (95%CI 1.30, 1.37); MCII was
      0.32 (0.30, 0.35) m/s. The HROM MCIP was 30.0 degrees  (29.4 degrees , 30.7
      degrees ); MCII was 13.3 degrees  (12.1 degrees , 14.8 degrees ). The adduction
      moment MCIP was 4.2% Body Weight * Height (4.0, 4.4); MCII was 0.87 (0.57, 1.17)
      % Body Weight * Height. Women were more likely to achieve MCII for HROM and MCIP
      for adduction moment (ORs 2.4-11.6, p <= 0.031). Lower BMI predicted HROM and
      adduction moment MCIPs (ORs 0.85-0.88, p <= 0.015). Lower preoperative HHS
      predicted speed, HROM and adduction moment MCIIs (ORs 0.95-0.97, p <= 0.012).
      With further validation, clinically-relevant gait benchmarks can enhance efforts
      to improve THA outcomes.

PMID- 26218745
TI  - CXCR4-targeted lipid-coated PLGA nanoparticles deliver sorafenib and overcome
      acquired drug resistance in liver cancer.
AB  - Sorafenib, a multikinase inhibitor, has been used as an anti-angiogenic agent
      against highly vascular hepatocellular carcinoma (HCC) - yet associated with only
      moderate therapeutic effect and the high incidence of HCC recurrence. We have
      shown intratumoral hypoxia induced by sorafenib activated C-X-C receptor type 4
      (CXCR4)/stromal-derived factor 1alpha (SDF1alpha) axis, resulting in polarization
      toward a tumor-promoting microenvironment and resistance to anti-angiogenic
      therapy in HCC. Herein, we formulated sorafenib in CXCR4-targeted lipid-coated
      poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with a CXCR4
      antagonist, AMD3100 to systemically deliver sorafenib into HCC and sensitize HCC
      to sorafenib treatment. We demonstrated that CXCR4-targeted NPs efficiently
      delivered sorafenib into HCCs and human umbilical vein endothelial cells (HUVECs)
      to achieve cytotoxicity and anti-angiogenic effect in vitro and in vivo. Despite
      the increased expression of SDF1alpha upon the persistent hypoxia induced by
      sorafenib-loaded CXCR4-targeted NPs, AMD3100 attached to the NPs can block
      CXCR4/SDF1alpha, leading to the reduced infiltration of tumor-associated
      macrophages, enhanced anti-angiogenic effect, a delay in tumor progression and
      increased overall survival in the orthotopic HCC model compared with other
      control groups. In conclusion, our results highlight the clinical potential of
      CXCR4-targeted NPs for delivering sorafenib and overcoming acquired drug
      resistance in liver cancer. 

PMID- 26218746
TI  - Changes in Dietary Behavior among Coronary and Hypertensive Patients: A
      Longitudinal Investigation Using the Health Action Process Approach.
AB  - BACKGROUND: Cardiovascular diseases (CVDs) are a major cause of worldwide
      morbidity and mortality. Nutrition plays an important role in the primary,
      secondary, and tertiary prevention of CVDs. The present longitudinal study used
      the Health Action Process Approach (HAPA) to investigate changes in dietary
      behavior in coronary patients (CPs) affected by acute coronary syndrome and
      hypertensive patients (HPs) affected by essential arterial hypertension. METHODS:
      CPs (N = 250) and HPs (N = 246) completed a questionnaire during three
      measurement points (baseline, 6-month follow-up, and 12-month follow-up).
      Statistical analyses included a repeated measures ANOVA and a multi-sample
      structural equation model. RESULTS: HPs showed no changes in dietary behavior,
      whereas CPs improved their nutrition at 6 months and then maintained the
      healthier diet. The multi-sample analysis indicated equivalence of the HAPA model
      for both patient populations. CONCLUSIONS: These findings provide further
      evidence for the generalisability of the HAPA model, shedding light on dietary
      behavior among CVD patients and particularly on hypertensive patients which has
      received little attention. Moreover, the equivalence of the model suggests that
      the process of change is almost identical for individuals who are at high risk
      for a coronary event (i.e. HPs) and individuals who have already had the event
      (i.e. CPs).

PMID- 26218736
TI  - The Identification of Circulating MiRNA in Bovine Serum and Their Potential as
      Novel Biomarkers of Early Mycobacterium avium subsp paratuberculosis Infection.
AB  - Mycobacterium avium subspecies paratuberculosis (MAP) is the aetiological agent
      of Johne's disease (JD), a chronic enteritis in ruminants that causes substantial
      economic loses to agriculture worldwide. Current diagnostic assays are hampered
      by low sensitivity and specificity that seriously complicate disease control; a
      new generation of diagnostic and prognostic assays are therefore urgently needed.
      Circulating microRNAs (miRNAs) have been shown to have significant potential as
      novel biomarkers for a range of human diseases, but their potential application
      in the veterinary sphere has been less well characterised. The aim of this study
      was therefore to apply RNA-sequencing approaches to serum from an experimental JD
      infection model as a route to identify novel diagnostic and prognostic miRNA
      biomarkers. Sera from experimental MAP-challenged calves (n = 6) and age-matched
      controls (n = 6) were used. We identified a subset of known miRNAs from bovine
      serum across all samples, with approximately 90 being at potentially functional
      abundance levels. The majority of known bovine miRNAs displayed multiple isomiRs
      that differed from the canonical sequences. Thirty novel miRNAs were identified
      after filtering and were found within sera from all animals tested. No
      significant differential miRNA expression was detected when comparing sera from
      MAP-challenged animals to their age-matched controls at six-month's post
      infection. However, comparing sera from pre-infection bleeds to six-month's post
      infection across all 12 animals did identify increased miR-205 (2-fold) and
      decreased miR-432 (2-fold) within both challenged and control groups, which
      suggests changes in circulating miRNA profiles due to ageing or development
      (P<0.00001). In conclusion our study has identified a range of novel miRNA in
      bovine serum, and shown the utility of small RNA sequencing approaches to explore
      the potential of miRNA as novel biomarkers for infectious disease in cattle. 

PMID- 26218743
TI  - Reversion of multidrug resistance by a pH-responsive cyclodextrin-derived
      nanomedicine in drug resistant cancer cells.
AB  - Multidrug resistance (MDR) is one of the major problems responsible for
      inefficiency of cancer chemotherapy. Currently, there is still unmet demand for
      innovative strategies as well as effective and safe sensitizers to overcome MDR.
      In this study, we developed a nanosensitizer based on a pH-responsive
      nanoparticle (NP) derived from acetalated alpha-cyclodextrin (Ac-aCD). This pH
      responsive NP could be effectively endocytosed by MDR cancer cells, and
      intracellularly transported by endolysosomal compartments. Ac-aCD NP was able to
      dramatically potentiate the activity of anticancer drugs including paclitaxel,
      docetaxel, cis-diamminedichloroplatinum, camptothecin, and doxorubicin. This
      sensitizing capability of Ac-aCD NP on MDR cells was resulted from the combined
      effects of decreased Pgp expression, attenuated Pgp ATPase activity, and the
      reduced intracellular ATP level. Ac-aCD NP exerted these diverse biological
      functions by intracellularly released alpha-cyclodextrin molecules, which were
      produced due to hydrolysis of Ac-aCD in acidic subcellular organelle. On the
      other hand, treatment with Ac-aCD NP showed no significant effects on the
      integrity of the plasma membrane, cytoskeleton, cell cycle, mitochondrial
      membrane potential, and apoptosis. These findings suggest that this pH-responsive
      NP has great potential for effective therapy of resistant cancers by combining
      with chemotherapeutic agents. It may also serve as a pharmacologically active
      nanocarrier for intracellular delivery of a plethora of antitumor drugs. 

PMID- 26218749
TI  - Ankle sprain: the effects of non-steroidal anti-inflammatory drugs.
AB  - INTRODUCTION: Injury of the lateral ligament complex of the ankle joint occurs in
      about one in 10,000 people per day, accounting for a quarter of all sports
      injuries. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to
      answer the following clinical question: What are the effects of non-steroidal
      anti-inflammatory drugs (NSAIDs) in the treatment of acute ankle sprains? We
      searched: Medline, Embase, The Cochrane Library, and other important databases up
      to April 2014 (Clinical Evidence overviews are updated periodically; please check
      our website for the most up-to-date version of this overview). RESULTS: At this
      update, searching of electronic databases retrieved 158 studies. After
      deduplication and removal of conference abstracts, 97 records were screened for
      inclusion in the overview. Appraisal of titles and abstracts led to the exclusion
      of 48 studies and the further review of 49 full publications. Of the 49 full
      articles evaluated, one systematic review and four RCTs were added. We performed
      a GRADE evaluation for four PICO combinations. CONCLUSIONS: In this systematic
      overview, we categorised the efficacy for three interventions, based on
      information relating to the effectiveness and safety of oral NSAIDs versus
      placebo, oral versus topical NSAIDs, selective COX-2 inhibitors versus other
      NSAIDs, and topical NSAIDs versus placebo.

PMID- 26218747
TI  - Neuropathic Pain Phenotype Does Not Involve the NLRP3 Inflammasome and Its End
      Product Interleukin-1beta in the Mice Spared Nerve Injury Model.
AB  - The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is one
      of the main sources of interleukin-1beta (IL-1beta) and is involved in several
      inflammatory-related pathologies. To date, its relationship with pain has not
      been studied in depth. The aim of our study was to elucidate the role of NLRP3
      inflammasome and IL-1beta production on neuropathic pain. Results showed that
      basal pain sensitivity is unaltered in NLRP3-/- mice as well as responses to
      formalin test. Spared nerve injury (SNI) surgery induced the development of
      mechanical allodynia and thermal hyperalgesia in a similar way in both genotypes
      and did not modify mRNA levels of the NLRP3 inflammasome components in the spinal
      cord. Intrathecal lipopolysaccharide (LPS) injection increases apoptosis
      associated speck like protein (ASC), caspase-1 and IL-1beta expression in both
      wildtype and NLRP3-/- mice. Those data suggest that NLRP3 is not involved in
      neuropathic pain and also that other sources of IL-1beta are implicated in
      neuroinflammatory responses induced by LPS. 

PMID- 26218752
TI  - Comparison of multibody and finite element human body models in pedestrian
      accidents with the focus on head kinematics.
AB  - OBJECTIVE: The objective of this study was to compare and evaluate the difference
      in head kinematics between the TNO and THUMS models in pedestrian accident
      situations. METHODS: The TNO pedestrian model (version 7.4.2) and the THUMS
      pedestrian model (version 1.4) were compared in one experiment setup and 14
      different accident scenarios where the vehicle velocity, leg posture, pedestrian
      velocity, and pedestrian's initial orientation were altered. In all simulations,
      the pedestrian model was impacted by a sedan. The head trajectory, head rotation,
      and head impact velocity were compared, as was the trend when various different
      parameters were altered. RESULTS: The multibody model had a larger head wrap
      around distance for all accident scenarios. The maximum differences of the head's
      center of gravity between the models in the global x-, y-, and z-directions at
      impact were 13.9, 5.8, and 5.6 cm, respectively. The maximum difference between
      the models in head rotation around the head's inferior-superior axis at head
      impact was 36 degrees . The head impact velocity differed up to 2.4 m/s between
      the models. The 2 models showed similar trends for the head trajectory when the
      various parameters were altered. CONCLUSIONS: There are differences in kinematics
      between the THUMS and TNO pedestrian models. However, these model differences are
      of the same magnitude as those induced by other uncertainties in the accident
      reconstructions, such as initial leg posture and pedestrian velocity.

PMID- 26218753
TI  - Skeletal Muscle to Pancreatic beta-Cell Cross-talk: The Effect of Humoral
      Mediators Liberated by Muscle Contraction and Acute Exercise on beta-Cell
      Apoptosis.
AB  - CONTEXT: Mechanisms explaining exercise-induced beta-cell health are unknown.
      OBJECTIVE: This study aimed to define the role of muscle contraction and acute
      exercise-derived soluble humoral mediators on beta-cell health. DESIGN: In vitro
      models were used. SETTING: University. PARTICIPANTS: Healthy subjects.
      INTERVENTION(S): Conditioned media (CM) were collected from human skeletal muscle
      (HSkM) cells treated with or without electrical pulse stimulation (EPS).
      Antecubital and femoral venous blood serum were collected before and after an
      exercise bout. CM and sera with or without IL-6 neutralization were used to
      incubate insulin-producing INS-1 cells and rat islets for 24 h in the presence or
      absence of proinflammatory cytokines (IL-1beta+IFN-gamma). MAIN OUTCOME
      MEASURE(S): INS-1 and islet apoptosis and accumulated insulin secretion. RESULTS:
      IL-1beta+IFN-gamma increased INS-1 and islet apoptosis and decreased insulin
      secretion. EPS-treated HSkM cell CM did not affect these variables. Exercise
      conditioned antecubital but not femoral sera prevented IL-1beta+IFN-gamma-induced
      INS-1 and islet apoptosis. Femoral sera reduced insulin secretion under normal
      and proinflammatory conditions in INS-1 but not islet cells. EPS increased HSkM
      cell IL-6 secretion and exercise increased circulating IL-6 levels in antecubital
      and femoral serum. IL-6 neutralization demonstrated that muscle-derived IL-6
      prevents INS-1 and islet apoptosis in the absence of IL-1beta+IFN-gamma, but
      augments apoptosis under proinflammatory conditions, and that muscle-derived IL-6
      supports islet insulin secretion in the absence of IL-1beta+IFN-gamma.
      CONCLUSIONS: Unidentified circulating humoral mediators released during exercise
      prevent proinflammatory cytokine-induced beta-cell apoptosis. Muscle-derived
      mediators released during exercise suppress beta-cell insulin secretion.
      Furthermore, muscle-derived IL-6 seems to prevent beta-cell apoptosis under
      normal conditions but contributes to beta-cell apoptosis under proinflammatory
      conditions.

PMID- 26218754
TI  - Neuroendocrine Morbidity After Pediatric Optic Gliomas: A Longitudinal Analysis
      of 166 Children Over 30 Years.
AB  - CONTEXT: Fifty percent of pediatric low-grade gliomas affect the optic pathway,
      hypothalamus, and suprasellar areas (OP/HSGs), resulting in significant long-term
      neuroendocrinopathy. OBJECTIVE: This study aimed to dissect tumor- from treatment
      related risk factors for OP/HSG-associated neuroendocrinopathy. DESIGN: This was
      a retrospective case notes analysis of 166 children with newly diagnosed OP/HSGs
      at our quaternary center between 1980 and 2010 by multivariate Cox, linear, and
      logistic regression. RESULTS: Patients were of median (range) age 4.9 (0.2-15.4)
      years at diagnosis and followed up for 8.3 (0.04-26.8) years. Despite high 20
      year overall survival (81.0%), progression-free and endocrine event-free survival
      (EEFS) were 47.2 and 20.8%, respectively. EEFS declined up to 15 years post
      diagnosis, with hypothalamic involvement (P < .001) being implicated more than
      radiotherapy (P = .008) in earlier endocrinopathy; the reverse being true of its
      density (radiotherapy P < .001; hypothalamic involvement P = .006). GH deficiency
      (GHD) was most common (40.3%), followed by central precocious puberty (CPP,
      26.0%), gonadotropin (GnD; 20.4%), TSH (13.3%), and ACTH (13.3%) deficiencies.
      GHD increased with later treatment eras (P < .01), but replacement did not
      increase progression. CPP was associated with future GnD (P < .05). Posterior
      pituitary dysfunction (PPD; 7.2%) occurred in 57.9% after only biopsies or shunt
      procedures, and was associated with 6/13 deaths; 50.2% became obese. Tumor
      extent, surgery, and increased endocrinopathy, rather than radiotherapy,
      predicted visuocognitive morbidity. CONCLUSIONS: This first longitudinal OP/HSG
      specific study demonstrates that hypothalamo-pituitary dysfunction evolves
      hierarchically over decades. Tumor location predicts its speed of onset and
      radiotherapy its density. GnD can evolve from previous CPP, whereas life
      threatening PPD can occur after any surgery. Our data suggest that recent
      radiation-avoiding chemotherapeutic strategies have increased GHD without
      improving survival.

PMID- 26218748
TI  - p21-Activated Kinases 1, 2 and 4 in Endometrial Cancers: Effects on Clinical
      Outcomes and Cell Proliferation.
AB  - p21-activated kinases (Paks) are serine/threonine protein kinases involved in
      biological events linked to malignant tumor progression. In this study,
      expression of Pak1, p-Pak2 Ser20, Pak4, pPak4 Ser474 in 21 normal endometrium, 16
      hyperplastic endometrium without atypia, 17 atypical complex hyperplasia and 67
      endometrial cancers was assessed by immunohistochemistry and correlated with
      clinicopathological parameters. We also accessed the proliferative role and
      downstream targets of Pak1 in endometrial cancer. Pak1 was expressed in cytoplasm
      whereas Pak4 and p-Pak4 were expressed in both cytoplasm and nucleus of
      endometrial tissues. In normal endometrium, significantly higher Pak1 (P = 0.028)
      and cytoplasmic p-Pak2 (P = 0.048) expression was detected in proliferative
      endometrium than secretory endometrium. Pak1, cytoplasmic and nuclear Pak4 and
      nuclear p-Pak4 was significantly overexpressed in endometrial cancer when
      compared to atrophic endometrium (all P<0.05). Moreover, type I endometrioid
      carcinomas showed significantly higher Pak1 expression than type II non
      endometrioid carcinomas (P<0.001). On the other hand, Pak1, Pak4 and p-Pak4
      expression negatively correlated with histological grade (all P<0.05) while p
      Pak2 and cytoplasmic Pak4 expression inversely correlated with myometrial
      invasion (all P<0.05). Furthermore, patients with endometrial cancers with lower
      cytoplasmic Pak4 expression showed poorer survival (P = 0.026). Multivariate
      analysis showed cytoplasmic Pak4 is an independent prognostic factor.
      Functionally, knockdown of Pak1, but not Pak4, in endometrial cancer cell line
      led to reduced cell proliferation along with reduced cyclin D1, estrogen receptor
      (ERalpha) and progestogen receptor (PR) expression. Significant correlation
      between Pak1 and PR expression was also detected in clinical samples. Our
      findings suggest that Pak1 and cytoplasmic p-Pak2 may promote cell proliferation
      in normal endometrium during menstral cycle. Pak1, cytoplasmic and nuclear Pak4
      and nuclear p-Pak4 are involved in the pathogenesis of endometrial cancer
      especially in postmenopausal women. Pak1 promote endometrial cancer cell
      proliferation, particular in type I endometrioid carcinoma. Cytoplasmic Pak4 can
      be potential prognostic marker in endometrial cancer. 

PMID- 26218751
TI  - Single fluoxetine treatment before but not after stress prevents stress-induced
      hippocampal long-term depression and spatial memory retrieval impairment in rats.
AB  - A growing body of evidence has shown that chronic treatment with fluoxetine, a
      widely prescribed medication for treatment of depression, can affect synaptic
      plasticity in the adult central nervous system. However, it is not well
      understood whether acute fluoxetine influences synaptic plasticity, especially on
      hippocampal CA1 long-term depression (LTD), and if so, whether it subsequently
      impacts hippocampal-dependent spatial memory. Here, we reported that LTD
      facilitated by elevated-platform stress in hippocampal slices was completely
      prevented by fluoxetine administration (10 mg/kg, i.p.) 30 min before stress. The
      LTD was not, however, significantly inhibited by fluoxetine administration
      immediately after stress. Similarly, fluoxetine incubation (10 MUM) during
      electrophysiological recordings also displayed no influence on the stress
      facilitated LTD. In addition, behavioral results showed that a single fluoxetine
      treatment 30 min before but not after acute stress fully reversed the impairment
      of spatial memory retrieval in the Morris water maze paradigm. Taken together,
      these results suggest that acute fluoxetine treatment only before, but not after
      stress, can prevent hippocampal CA1 LTD and spatial memory retrieval impairment
      caused by behavioral stress in adult animals. 

PMID- 26218756
TI  - Serum 8-isoprostane levels and paraoxonase 1 activity in patients with stage I
      multiple myeloma.
AB  - OBJECTIVE: Multiple myeloma (MM) is a plasma cell malignancy comprising 15% of
      hematological malignancies. Many studies have assessed the relationship between
      free radicals and tumor progression or cancer risk. We aimed to evaluate the
      antioxidant activity of paraoxonase 1 (PON1), arylesterase (ARE), and 8
      isoprostane in patients with stage I MM. MATERIALS AND METHODS:
      Spectrophotometric assays of serum PON1 and ARE activities in addition to serum 8
      isoprostane level were performed in 34 patients newly diagnosed with stage I MM
      as compared to 35 age- and sex-matched individuals who comprised the healthy
      control group. RESULTS: A significant reduction was found in the activities of
      PON1 and ARE (for both, P < 0.001) in the patient group. The ratio of PON1/high
      density lipoprotein was significantly lower in the MM patient group than in the
      control group (P < 0.001), while 8-isoprostane levels compared with the control
      group were significantly higher (P < 0.001), observations that may indicate an
      increase in oxidative stress in stage I MM patients. CONCLUSION: A decrease in
      PON1 activity and increase in 8-isoprostane serum activities in patients may
      indicate the importance of lipid peroxidation in MM disease. Oxidative stress and
      especially lipid peroxidation could reduce the antioxidant activity of PON1 and
      ARE in MM patients and could be considered as factors in the pathogenesis of MM
      disease.

PMID- 26218755
TI  - Impact of care at comprehensive cancer centers on outcome: Results from a
      population-based study.
AB  - BACKGROUND: Rigorous processes ensure quality of research and clinical care at
      National Cancer Institute-designated comprehensive cancer centers (NCICCCs).
      Unmeasurable elements of structure and process of cancer care delivery warrant
      evaluation. To the authors' knowledge, the impact of NCICCC care on survival and
      access to NCICCCs for vulnerable subpopulations remain unstudied. METHODS: The
      current study's population-based cohort of 69,579 patients had newly diagnosed
      adult-onset (aged 22-65 years) cancers reported to the Los Angeles County cancer
      registry between 1998 and 2008. Geographic information systems were used for
      geospatial analysis. RESULTS: With regard to overall survival across multiple
      diagnoses, patients not receiving their first planned treatment at NCICCCs
      experienced poorer outcomes compared with those treated at NCICCCs; differences
      persisted on multivariable analyses after adjusting for clinical and
      sociodemographic factors (hepatobiliary: hazard ratio [HR], 1.5; 95% confidence
      interval [95% CI], 1.4-1.7 [P<.001]; lung: HR, 1.4; 95% CI, 1.3-1.6 [P<.001];
      pancreatic: HR, 1.5; 95% CI, 1.3-1.7 [P<.001]; gastric: HR, 1.3; 95% CI, 1.1-1.7
      [P = .01]; breast: HR, 1.3; 95% CI, 1.1-1.5 [P<.001]; and colorectal: HR, 1.2;
      95% CI, 1.0-1.4 [P = .05]). With regard to barriers to care, multivariable
      analyses revealed that a lower likelihood of treatment at NCICCCs was associated
      with race/ethnicity (African-American: OR range across diagnoses: 0.4-0.7
      [P<.03]; Hispanic: OR range, 0.5-0.7 [P<.04]); lack of private insurance (public:
      OR range, 0.6-0.8 [P<.004]; uninsured: OR range, 0.1-0.5 [P<.04]); less than high
      socioeconomic status (high-middle: OR range, 0.4-0.7 [P<.02]; middle: OR range,
      0.3-0.5 [P<.001]; and low: OR range, 0.2-0.6 [P<.01]), and residing >9 miles from
      the nearest NCICCC (OR range, 0.5-0.7 [P<.02]). CONCLUSIONS: Among individuals
      aged 22 to 65 years residing in Los Angeles County with newly diagnosed adult
      onset cancer, those who were treated at NCICCCs experienced superior survival
      compared with those treated at non-NCICCC facilities. Barriers to care at NCICCCs
      included race/ethnicity, insurance, socioeconomic status, and distance to an
      NCICCC.

PMID- 26218758
TI  - Effect of Lycoris chejuensis and Its Active Components on Experimental Models of
      Alzheimer's Disease.
AB  - We found that an extract of Lycoris chejuensis and its three isolated active
      components, narciclasine, 7-deoxynarciclasine, and 7-deoxy-trans
      dihydronarciclasine, each significantly reduced the formation of amyloid-beta
      peptides in HeLa cells transfected with an amyloid precursor protein carrying the
      Swedish mutation up to 45 +/- 3.6%. The extract down-regulated amyloid precursor
      protein, especially the mature form by up to 88%, and reduced the ability of
      secretases to generate toxic amyloid-beta. Double-transgenic mice treated with
      the extract for 4 months also showed significantly reduced levels of amyloid-beta
      and plaques while exhibiting improved memory functions in the Morris water maze
      and novel object recognition tests. In conclusion, the extract and isolated
      active components of L. chejuensis decreased the production of amyloid-beta by
      attenuating amyloid precursor protein levels. Furthermore, the extract improved
      the disrupted memory functions in animals while inhibiting amyloid plaque
      formation. Thus, this extract, as well as its active components, could prove
      beneficial in the treatment of Alzheimer's disease. 

PMID- 26218744
TI  - Disulfide cross-linked micelles of novel HDAC inhibitor thailandepsin A for the
      treatment of breast cancer.
AB  - Histone deacetylase (HDAC) inhibitors are an emerging class of targeted therapy
      against cancers. Thailandepsin A (TDP-A) is a recently discovered class I HDAC
      inhibitor with broad anti-proliferative activities. In the present study, we
      aimed to investigate the potential of TDP-A in the treatment of breast cancer. We
      demonstrated that TDP-A inhibited cell proliferation and induced apoptosis in
      breast cancer cells at low nanomolar concentrations. TDP-A activated the
      intrinsic apoptotic pathway through increase of pro-apoptotic protein Bax,
      decrease of anti-apoptotic Bcl-2, and cleavage of caspase-3 and poly (ADP-ribose)
      polymerase (PARP). TDP-A also induced cell cycle arrest at the G2/M phase, and
      promoted the production of reactive oxygen species (ROS). We have successfully
      encapsulated TDP-A into our recently developed disulfide cross-linked micelles
      (DCMs), improving its water solubility and targeted delivery. TDP-A loaded DCMs
      (TDP-A/DCMs) possess the characteristics of high loading capacity (>20%, w/w),
      optimal and monodisperse particle size (16 +/- 4 nm), outstanding stability with
      redox stimuli-responsive disintegration, sustained drug release, and preferential
      uptake in breast tumors. In the MDA-MB-231 breast cancer xenograft model, TDP
      A/DCMs were more efficacious than the FDA-approved FK228 at well-tolerated doses.
      Furthermore, TDP-A/DCMs exhibited synergistic anticancer effects when combined
      with the proteasome inhibitor bortezomib (BTZ) loaded DCMs (BTZ/DCMs). Our
      results indicate that TDP-A nanoformulation alone or in combination with BTZ
      nanoformulation are efficacious against breast cancer. 

PMID- 26218750
TI  - Cul4A overexpression associated with Gli1 expression in malignant pleural
      mesothelioma.
AB  - Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer
      without an effective treatment. Cul4A, a scaffold protein that recruits
      substrates for degradation, is amplified in several human cancers, including
      mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro
      and in a mouse model. In this study, we analysed clinical mesothelioma tumours
      and found moderate to strong expression of Cul4A in 70.9% (51/72) of these
      tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with
      increased Cul4A copy number identified by fluorescence in situ hybridization
      analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was
      overexpressed and Cul4A copy number was increased in human mesothelioma cell
      lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared
      Cul4A and Gli1 expression in mesothelioma tumours and found their expression
      associated (P < 0.05, chi-square). In mesothelioma cell lines, inhibiting Cul4A
      by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least
      in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage
      between Cul4A and Gli1 expression in human mesothelioma.

PMID- 26218757
TI  - Safety and technological properties of bacteriocinogenic enterococci isolates
      from Tunisia.
AB  - AIMS: To investigate the safety and technological traits of previously isolated
      bacteriocinogenic enterococci strains for potential use as starter/adjunct
      cultures in foods. METHODS AND RESULTS: Fifty-five bacteriocinogenic enterococci
      strains previously isolated from different origins in Tunisia were screened for
      safety. Twenty-two strains did not harbour the genes coding for virulence traits,
      were susceptible to relevant antibiotics such as vancomycin, and tested negative
      for haemolysis, histamine production, gelatinase activity and DNase activity.
      These strains were further assessed for some technological properties,
      demonstrating low milk-acidifying ability, low proteolytic activity, high
      peptidolytic activity and diacetyl production in milk. CONCLUSIONS: This study
      revealed that 22 bacteriocinogenic enteroccoci strains did not present virulence
      features and could be safely applied in food preservation. Some strains also
      showed good technological potential as adjunct/protective cultures in milk
      fermentation and cheese production. SIGNIFICANCE AND IMPACT OF THE STUDY: This is
      one of very few studies that identified safe Enterococcus strains capable of
      producing a wide variety of enterocins against different spoilage and pathogenic
      micro-organisms that have good potential for application as adjunct/protective
      cultures in foods.

PMID- 26218764
TI  - Correction: CRISPR Content Correlates with the Pathogenic Potential of
      Escherichia coli.

PMID- 26218763
TI  - RS slope detection algorithm for extraction of heart rate from noisy, multimodal
      recordings.
AB  - Current gold-standard algorithms for heart beat detection do not work properly in
      the case of high noise levels and do not make use of multichannel data collected
      by modern patient monitors. The main idea behind the method presented in this
      paper is to detect the most prominent part of the QRS complex, i.e. the RS slope.
      We localize the RS slope based on the consistency of its characteristics, i.e.
      adequate, automatically determined amplitude and duration. It is a very simple
      and non-standard, yet very effective, solution. Minor data pre-processing and
      parameter adaptations make our algorithm fast and noise-resistant. As one of a
      few algorithms in the PhysioNet/Computing in Cardiology Challenge 2014, our
      algorithm uses more than two channels (i.e. ECG, BP, EEG, EOG and EMG). Simple
      fundamental working rules make the algorithm universal: it is able to work on all
      of these channels with no or only little changes. The final result of our
      algorithm in phase III of the Challenge was 86.38 (88.07 for a 200 record test
      set), which gave us fourth place. Our algorithm shows that current standards for
      heart beat detection could be improved significantly by taking a multichannel
      approach. This is an open-source algorithm available through the PhysioNet
      library. 

PMID- 26218737
TI  - A Global Perspective on Pyrazinamide Resistance: Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Pyrazinamide (PZA) is crucial for tuberculosis (TB) treatment, given
      its unique ability to eradicate persister bacilli. The worldwide burden of PZA
      resistance remains poorly described. METHODS: Systematic PubMed, Science Direct
      and Scopus searches for articles reporting phenotypic (liquid culture drug
      susceptibility testing or pyrazinamidase activity assays) and/or genotypic
      (polymerase chain reaction or DNA sequencing) PZA resistance. Global and regional
      summary estimates were obtained from random-effects meta-analysis, stratified by
      presence or risk of multidrug resistant TB (MDR-TB). Regional summary estimates
      were combined with regional WHO TB incidence estimates to determine the annual
      burden of PZA resistance. Information on single nucleotide polymorphisms (SNPs)
      in the pncA gene was aggregated to obtain a global summary. RESULTS: Pooled PZA
      resistance prevalence estimate was 16.2% (95% CI 11.2-21.2) among all TB cases,
      41.3% (29.0-53.7) among patients at high MDR-TB risk, and 60.5% (52.3-68.6) among
      MDR-TB cases. The estimated global burden is 1.4 million new PZA resistant TB
      cases annually, about 270,000 in MDR-TB patients. Among 1,815 phenotypically
      resistant isolates, 608 unique SNPs occurred at 397 distinct positions throughout
      the pncA gene. INTERPRETATION: PZA resistance is ubiquitous, with an estimated
      one in six incident TB cases and more than half of all MDR-TB cases resistant to
      PZA globally. The diversity of SNPs across the pncA gene complicates the
      development of rapid molecular diagnostics. These findings caution against
      relying on PZA in current and future TB drug regimens, especially in MDR-TB
      patients.

PMID- 26218762
TI  - Novel 10-kHz High-frequency Therapy (HF10 Therapy) Is Superior to Traditional Low
      frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain:
      The SENZA-RCT Randomized Controlled Trial.
AB  - BACKGROUND: Current treatments for chronic pain have limited effectiveness and
      commonly known side effects. Given the prevalence and burden of intractable pain,
      additional therapeutic approaches are desired. Spinal cord stimulation (SCS)
      delivered at 10 kHz (as in HF10 therapy) may provide pain relief without the
      paresthesias typical of traditional low-frequency SCS. The objective of this
      randomized, parallel-arm, noninferiority study was to compare long-term safety
      and efficacy of SCS therapies in patients with back and leg pain. METHODS: A
      total of 198 subjects with both back and leg pain were randomized in a 1:1 ratio
      to a treatment group across 10 comprehensive pain treatment centers. Of these,
      171 passed a temporary trial and were implanted with an SCS system. Responders
      (the primary outcome) were defined as having 50% or greater back pain reduction
      with no stimulation-related neurological deficit. RESULTS: At 3 months, 84.5% of
      implanted HF10 therapy subjects were responders for back pain and 83.1% for leg
      pain, and 43.8% of traditional SCS subjects were responders for back pain and
      55.5% for leg pain (P < 0.001 for both back and leg pain comparisons). The
      relative ratio for responders was 1.9 (95% CI, 1.4 to 2.5) for back pain and 1.5
      (95% CI, 1.2 to 1.9) for leg pain. The superiority of HF10 therapy over
      traditional SCS for leg and back pain was sustained through 12 months (P <
      0.001). HF10 therapy subjects did not experience paresthesias. CONCLUSION: HF10
      therapy promises to substantially impact the management of back and leg pain with
      broad applicability to patients, physicians, and payers.

PMID- 26218759
TI  - Variation in treatment strategies of Swiss general practitioners for subclinical
      hypothyroidism in older adults.
AB  - QUESTIONS UNDER STUDY: As the best management of subclinical hypothyroidism is
      controversial, we aimed to assess variations in treatment strategies depending on
      different Swiss regions, physician and patient characteristics. METHODS: We
      performed a case-based survey among general practitioners (GPs) in different
      Swiss regions, which consisted of eight hypothetical cases presenting a female
      patient with subclinical hypothyroidism and nonspecific complaints differing by
      age, vitality status and thyroid-stimulating hormone (TSH) concentration.
      RESULTS: A total of 262 GPs participated in the survey. There was considerable
      variation in the levothyroxine starting dose chosen by GPs, ranging from 25 ug to
      100 ug. Across the Swiss regions, GPs in the Bern region were significantly more
      inclined to treat, with a higher probability of initiating treatment (60%, p =
      0.01) and higher mean starting doses (45 ug, p <0.01) compared with the French
      speaking region (44%, 36 ug); the Zurich region had intermediate values (52%, 39
      ug). We found no association between treatment rate and other physician
      characteristics. GPs were more reluctant to initiate treatment in 85-year-old
      than in 70-year-old women (odds ratio [OR] 0.77, 95% confidence interval [CI]
      0.63-0.94), and more likely to treat women with a TSH of 15 mU/l than those with
      a TSH of 6mU/l (OR 8.71, 95% CI 6.21-12.20). CONCLUSIONS: There are strong
      variations in treatment strategies for elderly patients with subclinical
      hypothyroidism across different Swiss regions, including use of higher starting
      doses than the recommended 25 ug in the Swiss guidelines, which recommend a
      starting dose of 25 ug. These variations likely reflect the current uncertainty
      about the benefits of treatment, which arise from the current lack of evidence
      from adequately powered clinical trials.

PMID- 26218767
TI  - A 'One Stop' Prostate Clinic for rural and remote men: a report on the first 200
      patients.
AB  - OBJECTIVE: To report on the structure and outcomes of a new 'One Stop' Prostate
      Clinic (OSPC) designed specifically for rural and remote men. PATIENTS AND
      METHODS: Prospective cohort study of the first 200 rural or remote men to access
      a new OSPC at a public tertiary-level hospital in Western Australia between
      August 2011 and August 2014. Men attended for urological assessment, and
      proceeded to same-day transrectal ultrasonography-guided prostate biopsies, if
      appropriate. Referral criteria were either two abnormal age-related prostate
      specific antigen (PSA) levels in the absence of urinary tract infection (UTI), or
      an abnormal digital rectal examination (DRE) regardless of PSA level. RESULTS:
      The median (range) distance travelled was 1545 (56-3229) km and median (range)
      time from referral to assessment was 33 (2-165) days. The median (range) age was
      62 (38-85) years, PSA level was 6.7 (0.5-360) ng/mL and 39% (78/200) had a
      suspicious DRE. In all, 92% (184/200) of men proceeded to prostate biopsies, and
      60% (111/184) of these men were diagnosed with prostate cancer. Our complication
      rate was 3.5% (6/172). Radical prostatectomy (46/111), active surveillance
      (28/111) and external beam radiation therapy (26/111) were the commonest
      subsequent treatment methods. A $1045 (Australian dollars) cost-saving per person
      was estimated based on the reduced need for travel with the OSPC model.
      CONCLUSION: The OSPC is an effective and efficient model for assessing men
      suspected of having prostate cancer living in rural and remote areas of Western
      Australia, and this model may be applicable to other areas.

PMID- 26218766
TI  - Evolution of testosterone treatment over 25 years: symptom responses, endocrine
      profiles and cardiovascular changes.
AB  - INTRODUCTION: Testosterone treatment has evolved rapidly over the past 25 years
      as new, more effective and convenient methods have become available. This study
      reports experience with seven different methods, introduced on the market in the
      UK. AIM: To establish the symptom response when testosterone treatment was
      initiated on the basis of clinical features and symptoms of androgen deficiency,
      and the resulting endocrine, biochemical and physiological responses. METHODS: Of
      2693 patients attending the 3 Men's Health Centers - The UK Androgen Study
      (UKAS), 2247 were treated. Treatments included pellet implants, oral testosterone
      undecanoate (Testocaps), mesterolone (Proviron), testosterone gel (Testogel),
      testosterone scrotal cream (Andromen) and scrotal gel (Tostran). RESULTS: There
      was no correlation between initial testosterone level, initial symptom score or
      the success of treatment as defined by adequate resolution of symptoms. Despite
      the diverse endocrine patterns produced, the testosterone preparations appear
      equally safe over prolonged periods, with either no change or improvement of
      cardiovascular risk factors, especially in lowering cholesterol and diastolic
      blood pressure. CONCLUSIONS: It is suggested that because of excessive reliance
      on laboratory measures of androgens and undue safety concerns, many men who could
      benefit from symptom relief, improvement in related clinical conditions and given
      preventive medical benefits remain untreated.

PMID- 26218761
TI  - CTRP3 Stimulates Proliferation and Anti-Apoptosis of Prostate Cells through PKC
      Signaling Pathways.
AB  - C1q/TNF-related protein-3 (CTRP3) is a novel adipokine with roles in multiple
      cellular processes. However, little is known about its function in prostate
      cells. This study investigated the effects and mechanisms of CTRP3 in prostate
      cells. We first generated and purified CTRP3 protein in HEK 293T cells.
      Proliferation of RWPE-1 prostate cells was evaluated by MTT analyses under
      treatment with different concentrations of CTRP3 for various exposure times. The
      results revealed maximum enhancement of proliferation with 10 MUg/mL CTRP3 for 72
      h. Cell apoptosis and cell cycle were determined by TUNEL staining and flow
      cytometry analysis. TUNEL assay showed decreased TUNEL-positive cells in RWPE-1
      prostate cells treated with CTRP3, and flow cytometry showed significantly
      decreased apoptotic cells upon CTRP3 treatment (treated cells, 8.34+/-1.175 vs.
      controls, 20.163+/-0.35) (P < 0.01). Moreover, flow cytometry analysis also
      showed a significant decrease of cells in the G1 phase and an increase of cells
      in the S and G2 phase upon CTRP3 treatment (treated cells, 42.85+/-1.40 vs.
      control, 52.77+/-0.90; 28.41+/-0.57 vs. 23.49+/-1.13; 27.08+/-1.97 vs. 22.20+/
      1.32, respectively) (all P < 0.05). Two-dimensional gel electrophoresis and mass
      spectrometry identified differentially expressed proteins, including cytokeratin
      19, GLRX3 and DDAH1, which were upregulated in CTRP3 treated cells, and
      cytokeratin-17 and 14-3-3 sigma, which were downregulated. GLRX3, DDAH1 and 14-3
      3 sigma were confirmed using western blot analysis. A PKC inhibitor,
      staurosporine, was used to inhibit PKC activity in CTRP3 treated RWPE-1 cells.
      Staurosporine completely abolished the CTRP3-induced increased phosphorylation of
      intracellular PKC substrates and CTRP3-stimulated effect by RWPE-1 cells. Our
      results provide the first evidence for a physiological role of the novel
      adipokine, CTRP3, in prostate cells. Our findings suggest that CTRP3 could
      improve proliferation and anti-apoptosis of prostate cells through protein kinase
      C signaling pathways. 

PMID- 26218771
TI  - Determination of alkylresorcinols and their metabolites in biological samples by
      gas chromatography-mass spectrometry.
AB  - High throughput GC-MS methods for quantification of alkylresorcinols (AR),
      biomarkers of whole grain wheat and rye intake, in plasma and adipose tissue and
      their metabolites in urine were developed and optimised. Alkylresorcinols in
      plasma (200MUL) and adipose tissues (10-50mg) were extracted with diethyl ether,
      whereas main AR metabolites such as DHBA and DHPPA and newly identified
      metabolites in urine (50MUL) were extracted with ethyl acetate after enzymatic
      deconjugation. All extracts were purified on OASIS-MAX solid phase extraction
      cartridges. Plasma and adipose tissue sample extracts were then derivatised with
      trifluoroacetic anhydride and reconstituted in undecane, whereas AR metabolites
      in urine samples were derivatised with BSTFA+TMCS (99:1, v/v, 100MUL). Prepared
      samples were quantified by GC-MS (EI-SIM). Analysis of all compounds in the
      different matrices showed good selectivity, sensitivity, linearity, precision
      (<15% within and between batches), adequate recovery (75-108%), and short total
      run time (10-12min). The methods developed are applicable to large-scale sample
      sets such as epidemiological studies. 

PMID- 26218769
TI  - Metabolic profiling of breast cancer: Differences in central metabolism between
      subtypes of breast cancer cell lines.
AB  - Although the concept of aerobic glycolysis in cancer was already reported in the
      1930s by Otto Warburg, the understanding of metabolic pathways remains
      challenging especially due to the heterogeneity of cancer. In consideration of
      four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling
      of metabolites was performed on cell extracts and supernatants of breast cancer
      cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the
      breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct
      methanolic extraction, cell scraping and cell disruption was executed to obtain
      central metabolites. Major differences in biochemical pathways have been observed
      in the breast cancer cell lines compared to the breast epithelial cell line, as
      well as between the breast cancer cell lines themselves. Characteristics of
      breast cancer subtypes could be correlated to their individual metabolic
      profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF
      10A based on elevated amino acid levels. The observed metabolic signatures have
      great potential as biomarker for breast cancer as well as an improved
      understanding of subtype specific phenomenons of breast cancer. 

PMID- 26218765
TI  - Patterns of Neuropsychological Profile and Cortical Thinning in Parkinson's
      Disease with Punding.
AB  - BACKGROUND: Punding, one of dopamine replacement treatment related complications,
      refers to aimless and stereotyped behaviors. To identify possible neural
      correlates of punding behavior in patients with Parkinson's disease (PD), we
      investigated the patterns of cognitive profiles and cortical thinning. METHODS:
      Of the 186 subjects with PD screened during the study period, we prospectively
      enrolled 10 PD patients with punding and 43 without punding on the basis of a
      structured interview. We performed comprehensive neuropsychological tests and
      voxel-based and regions-of-interest (ROIs)-based cortical thickness analysis
      between PD patients with and without punding. RESULTS: The prevalence of punding
      in patients with PD was 5.4%. Punding behaviors were closely related to previous
      occupations or hobbies and showed a temporal relationship to changes of levodopa
      equivalent dose (LED). Significant predisposing factors were a long duration of
      PD and intake of medications of PD, high total daily LED, dyskinesia, and impulse
      control disorder. Punding severity was correlated with LED (p = 0.029). The
      neurocognitive assessment revealed that PD patients with punding showed more
      severe cognitive deficits in the color Stroop task than did those without punding
      (p = 0.022). Voxel-based analysis showed that PD-punders had significant cortical
      thinning in the dorsolateral prefrontal area relative to controls. Additionally,
      ROI-based analysis revealed that cortical thinning in PD-punders relative to PD
      nonpunders was localized in the prefrontal cortices, extending into orbitofrontal
      area. CONCLUSIONS: We demonstrated that PD patients with punding performed poorly
      on cognitive tasks in frontal executive functions and showed severe cortical
      thinning in the dorsolateral prefrontal and orbitofrontal areas. These findings
      suggest that prefrontal modulation may be an essential component in the
      development of punding behavior in patients with PD.

PMID- 26218785
TI  - Effects of Transcutaneous Electrical Acupoint Stimulation on Patients with Stable
      Chronic Obstructive Pulmonary Disease: A Prospective, Single-Blind, Randomized,
      Placebo-Controlled Study.
AB  - OBJECTIVES: To evaluate the clinical effect of transcutaneous electrical nerve
      stimulation over acupoints (acu-TENS) on patients with stable chronic obstructive
      pulmonary disease (COPD). DESIGN: Prospective, single-blind, randomized, placebo
      controlled study. Settings/Locations: Outpatient center of West China Hospital,
      Sichuan University. PATIENTS: Fifty patients with stable COPD enrolled in the
      study. INTERVENTIONS: Patients were randomly assigned to one of two groups: the
      acu-TENS group (n=25), who underwent acu-TENS over acupoints of bilateral EX-B
      1(Dingchuan), BL-13 (Feishu), BL-23 (Shenshu), ST-36 (Zusanli), and the placebo
      acu-TENS control group (n=25), who had the same electrode placement but no
      electrical output. Treatments were performed for 40-minute sessions every 2 days
      for 4 weeks. OUTCOME MEASURES: Lung function (forced expiratory volume in 1
      second, percentage predicted (FEV(1)% predicted); forced vital capacity,
      percentage predicted (FVC% predicted), 6-minute walk distance (6MWD) and oxygen
      saturation (SpO(2)), COPD assessment test (CAT), and Dyspnea Visual Analogue
      Scale (DVAS) were assessed before and after the intervention. RESULTS: Compared
      to control group, FEV(1)% predicted was improved and CAT score was decreased
      significantly in the acu-TENS group after treatment (p<0.05). The DVAS score
      decreased significantly in the acu-TENS group (p=0.039), with a slight but
      insignificant improve in 6MWD, SpO(2), and FVC% predicted after treatment.
      CONCLUSIONS: Acu-TENS over acupoints of bilateral EX-B-1 (Dingchuan), BL-13
      (Feishu), BL-23 (Shenshu), and ST-36 (Zusanli) improved FEV(1)% predicted and
      reduced DVAS and CAT scores on patients with stable COPD. This may be a novel
      treatment strategy in COPD.

PMID- 26218792
TI  - Rifaximin (Xifaxan) for irritable bowel syndrome with diarrhea.

PMID- 26218772
TI  - A Survival Analysis of Psychostimulant Prescriptions in New South Wales from 1990
      to 2010.
AB  - OBJECTIVE: Psychostimulant medication is considered a mainstay in the treatment
      of attention-deficit/hyperactivity disorder (ADHD); however, research suggests
      that the typical duration of medication treatment for children and youth may be
      <3 years. The purpose of this study was to evaluate the psychostimulant treatment
      persistence for children and adolescents in New South Wales, Australia. METHODS:
      This study used survival analysis to assess duration of medication treatment on a
      large administrative database of children and youth from New South Wales,
      Australia. Several models were fit to evaluate differences in survival rates
      among decades (1990-1999 vs. 2000-2010), gender, and age. RESULTS: Results showed
      that: 1) Overall median treatment time (i.e., median survival time) was 1.96
      years (99% CI=1.93, 1.99); 2) there were small, but significant changes over time
      in duration of treatment; 3) females had shorter treatment duration than males;
      and 4) there were relatively large differences in treatment duration across age
      groups. CONCLUSIONS: These results indicate that the majority of children and
      youth receive medication treatment for only a small portion of
      childhood/adolescence, and that there are differential patterns in treatment
      duration across age groups.

PMID- 26218760
TI  - Childhood Conscientiousness and Leukocyte Telomere Length 40 Years Later in Adult
      Women--Preliminary Findings of a Prospective Association.
AB  - Leukocyte telomere length (LTL) shortens with age, and is a prospective marker of
      mortality related to cardiovascular disease. Many health behaviors and social
      environmental factors have been found to be associated with LTL. Several of these
      are also associated with conscientiousness, a dispositional personality trait.
      Conscientiousness is a propensity to be planful, adhere to social norms, and
      inhibit pre-potent responses. Like LTL, conscientiousness is prospectively
      related to mortality, possibly through cumulative effects on health over the life
      course via multiple pathways. As a result, we hypothesized that childhood levels
      of conscientiousness would predict LTL prospectively in adulthood. We selected a
      sample of 60 women in the Hawaii Personality and Health Cohort; 30 described by
      their teachers as high on conscientiousness in childhood and 30 described as low
      on the trait. Dried blood spot samples collected in adulthood 40 years later were
      used as sources of DNA for the LTL assay. Conscientiousness was associated with
      longer LTL (p = .02). Controlling for age did not account for this association.
      Controlling for education and physiological dysregulation partially attenuated
      the association, and the effect remained significant when accounting for
      differences in LTL across cultural groups. These results represent the first
      evidence that childhood personality prospectively predicts LTL 40 years later in
      adulthood. Our findings would be consistent with a mediation hypothesis whereby
      conscientiousness predicts life paths and trajectories of health that are
      reflected in rates of LTL erosion across the lifespan. 

PMID- 26218768
TI  - Anti-angiogenesis therapy and gap junction inhibition reduce MDA-MB-231 breast
      cancer cell invasion and metastasis in vitro and in vivo.
AB  - Cancer cells secrete VEGF, which plays a key role in their growth, invasion,
      extravasation and metastasis. Direct cancer cell-endothelial cell interaction,
      mediated by gap junctions, is of critical importance in the extravasation
      process. In this study, we evaluated avastin (Av), an anti-VEGF antibody; and
      oleamide (OL), a gap junction inhibitor, using MDA-MB-231 human breast cancer
      cells in vitro and a xenograft murine model in vivo. Results showed that Av/OL
      significantly decreased proliferation, induced cell cycle arrest and decreased
      migration and invasion of MDA-MB-231 cells in vitro. In addition, Av/OL
      significantly decreased homo and hetero-cellular communication interaction
      between MDA-MDA and MDA-endothelial cells, respectively. The expression levels of
      several factors including VEGF, HIF1alpha, CXCR4, Cx26, Cx43, and MMP9 were
      attenuated upon Av/OL treatment in vitro. On the other hand, avastin, but not
      oleamide, reduced tumor size of NSG mice injected subdermally (s.d.) with MDA-MB
      231 cells, which was also associated with increased survival. Furthermore, Av but
      also OL, separately, significantly increased the survival rate, and reduced
      pulmonary and hepatic metastatic foci, of intravenously (i.v.) injected mice.
      Finally, OL reduced MMP9 protein expression levels, better than Av and in
      comparisons to control, in the lungs of MDA-MB-231 i.v. injected NSG mice. In
      conclusion, while avastin has anti-angiogenic, anti-tumor and anti-metastatic
      activities, oleamide has anti-metastatic activity, presumably at the
      extravasation level, providing further evidence for the role of gap junction
      intercellular communication (GJIC) in cancer cell extravasation. 

PMID- 26218770
TI  - Quantitative hydrophilic interaction chromatography-mass spectrometry analysis of
      N-acetylneuraminic acid and N-acetylmannosamine in human plasma.
AB  - N-acetylneuraminic acid (Neu5Ac or NANA) is the most predominant sialic acid in
      mammals. As a terminal component in many glycoproteins and glycolipids, sialic
      acid is believed to be an important biomarker related to various diseases. Its
      precursor, N-acetylmannosamine (ManNAc), is being investigated as a potential
      treatment for GNE myopathy. In this work, we developed two highly sensitive and
      selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for
      the quantitation of ManNAc and free Neu5Ac in human plasma. A fit-for-purpose
      approach was adopted during method validation and sample analysis. To measure the
      endogenous compounds and overcome the interference from plasma samples, a
      surrogate matrix that contained 5% bovine serum albumin (BSA) was used for the
      preparation of calibration standards and certain levels of quality control (QC)
      samples. QC samples at higher concentrations were prepared in the authentic
      matrix (human plasma) to best mimic incurred samples. For both methods, an Ostro
      96-well phospholipid removal plate was used for sample extraction, which
      efficiently removed the phospholipids from the plasma samples prior to LC
      injection, eliminated matrix effect, and improved sensitivity. Chromatographic
      separation was achieved using hydrophilic interaction chromatography (HILIC) and
      gradient elution in order to retain the two polar compounds. The lower limit of
      quantitation (LLOQ) for ManNAc and Neu5Ac was 10.0 and 25.0ng/mL, respectively.
      The overall accuracy of the two assays was within 100%+/-8.3% based on three
      levels of QC samples. Inter- and intra-run precision (coefficient of variation
      (%CV)) across three analytical runs was less than 6.7% for ManNAc and less than
      10.8% for Neu5Ac. These methods have been validated to support clinical studies. 

PMID- 26218787
TI  - Rapid mechanochemical synthesis of VOx/TiO2 as highly active catalyst for HCB
      removal.
AB  - A rapid (1.5h) one-step ball milling (BM) method was developed to synthesize
      VOx/TiO2 (VTi-BM) and WOx or MoOx doped VOx/TiO2 (VWTi-BM or VMoTi-BM). Catalytic
      activity on gaseous POPs removal was tested using hexachlorobenzene (HCB) as
      surrogate. Catalytic performance decreased in the order of VWTi-BM (T50%=230
      degrees C)>VMoTi-BM (260 degrees C)>VTi-BM (270 degrees C)>VTi-WI (300 degrees C;
      VOx/TiO2 synthesized by wetness impregnation method). The intermediates from
      oxidation of HCB were analyzed by off gas analysis, from which 2,2,4,5
      tetrachloro-4-cyclopentene-1,3-dione (TCCD), dichloromaleic anhydride (DCMA) and
      tetrachloro-1,4-bezoquinone (TCBQ) were identified. Furthermore, a possible
      mechanism for the oxidation of HCB over VOx/TiO2 catalysts was proposed.
      Mechanism studies showed that BM samples possess better dispersion of the VOx
      species and more surface chemisorbed oxygen. Doping WOx or MoOx into VOx/TiO2 by
      ball milling can further enhance catalytic performance by increasing surface acid
      sites. 

PMID- 26218774
TI  - Ligand-Modified Human Serum Albumin Nanoparticles for Enhanced Gene Delivery.
AB  - The development of nonviral gene delivery systems is a great challenge to enable
      safe gene therapy. In this study, ligand-modified nanoparticles based on human
      serum albumin (HSA) were developed and optimized for an efficient gene therapy.
      Different glutaraldehyde cross-linking degrees were investigated to optimize the
      HSA nanoparticles for gene delivery. The peptide sequence arginine-glycine
      aspartate (RGD) and the HIV-1 transactivator of transduction sequence (Tat) are
      well-known as promising targeting ligands. Plasmid DNA loaded HSA nanoparticles
      were covalently modified on their surface with these different ligands. The
      transfection potential of the obtained plasmid DNA loaded RGD- and Tat-modified
      nanoparticles was investigated in vitro, and optimal incubation conditions for
      these preparations were studied. It turned out that Tat-modified HSA
      nanoparticles with the lowest cross-linking degree of 20% showed the highest
      transfection potential. Taken together, ligand-functionalized HSA nanoparticles
      represent promising tools for efficient and safe gene therapy. 

PMID- 26218786
TI  - Antiquity of the South Atlantic Anomaly and evidence for top-down control on the
      geodynamo.
AB  - The dramatic decay of dipole geomagnetic field intensity during the last 160
      years coincides with changes in Southern Hemisphere (SH) field morphology and has
      motivated speculation of an impending reversal. Understanding these changes,
      however, has been limited by the lack of longer-term SH observations. Here we
      report the first archaeomagnetic curve from southern Africa (ca. 1000-1600 AD).
      Directions change relatively rapidly at ca. 1300 AD, whereas intensities drop
      sharply, at a rate greater than modern field changes in southern Africa, and to
      lower values. We propose that the recurrence of low field strengths reflects core
      flux expulsion promoted by the unusual core-mantle boundary (CMB) composition and
      structure beneath southern Africa defined by the African large low shear velocity
      province (LLSVP). Because the African LLSVP and CMB structure are ancient, this
      region may have been a steady site for flux expulsion, and triggering of
      geomagnetic reversals, for millions of years. 

PMID- 26218789
TI  - Combining 2 nm Spatial Resolution and 0.02% Precision for Deformation Mapping of
      Semiconductor Specimens in a Transmission Electron Microscope by Precession
      Electron Diffraction.
AB  - Precession electron diffraction has been used to provide accurate deformation
      maps of a device structure showing that this technique can provide a spatial
      resolution of better than 2 nm and a precision of better than 0.02%. The
      deformation maps have been fitted to simulations that account for thin specimen
      relaxation. By combining the experimental deformation maps and simulations, we
      have been able to separate the effects of the stressor and recessed sources and
      drains and show that the Si3N4 stressor increases the in-plane deformation in the
      silicon channel from 0.92 to 1.52 +/- 0.02%. In addition, the stress in the
      deposited Si3N4 film has been calculated from the simulations, which is an
      important parameter for device design. 

PMID- 26218794
TI  - Duopa--a carbidopa/levodopa enteral suspension for Parkinson's disease.

PMID- 26218791
TI  - Sacubitril/valsartan (Entresto) for heart failure.

PMID- 26218788
TI  - Feedback and therapist effects in the context of treatment outcome and treatment
      length.
AB  - OBJECTIVE: This study estimates feedback and therapist effects and tests the
      predictive value of therapists' and patient attitudes toward psychometric
      feedback for treatment outcome and length. METHODS: Data of 349 outpatients and
      44 therapists in private practices were used. Separate multilevel analyses were
      conducted to estimate predictors and feedback and therapist effects. RESULTS:
      Around 5.88% of the variability in treatment outcome and 8.89% in treatment
      length were attributed to therapists. There was no relationship between the
      average effectiveness of therapists and the average length of their treatments.
      Initial impairment, early alliance, number of diagnoses, feedback as well as
      therapists' and patients' attitudes toward feedback were significant predictors
      of treatment outcome. Treatments tended to be longer for patients with a higher
      number of approved sessions by the insurance company, with higher levels of
      interpersonal distress at intake, and for those who developed negatively
      (negative feedback) over the course of their treatment. CONCLUSIONS: Therapist
      effects on treatment outcome and treatment length in routine care seem to be
      relevant predictors in the context of feedback studies. Therapists' attitudes
      toward and use of feedback as well as patients' attitudes toward feedback should
      be further investigated in future research on psychometric feedback.

PMID- 26218795
TI  - Higher methylation of the IGF1 P2 promoter is associated with idiopathic short
      stature.
AB  - BACKGROUND: Idiopathic short stature (ISS) has a strong familial component, but
      genetics explains only part of it. Indeed, environmental factors act on human
      growth either directly or through epigenetic factors that remain to be
      determined. Given the importance of the GH/IGF1 axis for child growth, we
      suspected that such epigenetic factors could involve the CG methylation at the
      IGF1 gene P2 promoter, which was recently shown to be a transcriptional regulator
      for IGF1 gene and a major contributor to GH sensitivity. OBJECTIVE: Explore
      whether the methylation of the two IGF1 low-CG-rich promoters (P1 and P2) is
      associated with ISS. SUBJECTS AND METHODS: A total of 94 children with ISS were
      compared with 119 age-matched children of normal height for the methylation of
      CGs located within the IGF1 promoters measured with bisulphite PCR
      pyrosequencing. RESULTS: The methylation of 5 CGs of the P2 promoter was higher
      in ISS children, notably CG-137 (49 +/- 4% in ISS vs 46 +/- 4 % in control
      children, P = 9 * 10-5 ). This was also true for CG-611 of the P1 promoter (93 +/
      3% vs 91 +/- 3% P = 10-4 ). The CG methylation of the IGF1 promoters thus takes
      place among the multifactorial factors that are associated with ISS.

PMID- 26218793
TI  - Polidocanol (Varithena) for varicose veins.

PMID- 26218790
TI  - Microarray based screening of peptide nano probes for HER2 positive tumor.
AB  - Peptides are excellent biointerface molecules and diagnostic probes with many
      advantages such as good penetration, short turnover time, and low cost. We report
      here an efficient peptide screening strategy based on in situ single bead
      sequencing on a microarray. Two novel peptides YLFFVFER (H6) and KLRLEWNR (H10)
      specifically binding to the tumor biomarker human epidermal growth factor
      receptor 2 (HER2) with aKD of 10(-8) M were obtained from a 10(5) library.
      Conjugated to nanoparticles, both the H6 and H10 probes showed specific
      accumulation in HER2-positive tumor tissues in xenografted mice by in vivo
      imaging. 

PMID- 26218802
TI  - Identification of crucial genes in ventilator associated pneumonia through
      protein-protein interaction network.
AB  - PURPOSE: Ventilator-associated pneumonia (VAP) is still an important cause of
      morbidity and mortality in patients receiving mechanical ventilation. This
      research aimed to investigate the genes related to VAP and potential diagnosis
      targets. MATERIALS AND METHODS: Gene expression profiles data of GSE30385 were
      downloaded from Gene Expression Omnibus, which included 10 samples of patients
      with VAP and 10 samples of patients without VAP. The differentially expressed
      genes (DEGs) between two types of patients were identified by limma package and
      the functions and pathways of DEGs were predicted by Gene Ontology and KEGG
      pathway enrichment analyses. Next, the protein-protein interaction (PPI) pairs of
      all genes in the samples were obtained from STRING database. Then we searched
      genes related to VAP in NCBI, and constructed a PPI network of these genes.
      Subsequently, the overlapped genes between genes in the PPI network and DEGs were
      searched, followed by expression patterns analysis. Furthermore, genes in PPI
      network were subjected to function and pathway enrichment analysis, and
      transcription factors were screened on the basis of TRANSFAC database. RESULT: A
      total of 69 DEGs were screened between two types of patient samples, and 7 genes
      related to VAP were obtained. The overlapped genes (e.g. LTF, MAPK14) were
      enriched in MAPK cascade and immune system-related processes. In addition, MAPK14
      was enriched in MAPK signaling pathway. CONCLUSION: The VAP-related genes (MAPK14
      and LTF) might be the crucial genes in the pathogenesis of VAP, and be served as
      potential diagnostic targets.

PMID- 26218796
TI  - The Association between Dietary Patterns and Semen Quality in a General Asian
      Population of 7282 Males.
AB  - OBJECTIVE: To explore the associations between different dietary patterns and
      semen quality in a general Asian male population. METHODS: Cross-sectional study.
      Healthy Taiwanese men aged 18 years or older who participated in a standard
      medical screening program from 2008-2013 run by a private firm were included in
      this study. Semen parameters including sperm concentration (SC), total sperm
      motility (TSM), progressive motility (PRM) and normal sperm morphology (NSM) were
      recorded. A dietary questionnaire was used to categorize the participants into 5
      groups: "Healthy diet", "Western diet", "High-carbohydrate diet", "High sweet
      snacks & sugar-sweetened drinks" and "High-sodium diet". RESULTS: A total of 7282
      men completed the questionnaire regarding dietary pattern, and examination of
      anthropometric indexes was performed and laboratory data were obtained. A high
      intake of a "Western diet" resulted in statistically linear declines of SC and
      NSM (P < 0.001 and P < 0.001). Similarly, a greater intake of "High sweet snacks
      & sugar-sweetened drinks" was associated with a lower SC (P = 0.001). Increased
      intake of a "High-carbohydrate diet" was related to higher prevalences of
      abnormal TSM and PRM (P = 0.012 and P = 0.025). Similarly, a greater intake of a
      "High-sodium diet" was correlated with an elevated prevalence of abnormal NSM (P
      = 0.035). CONCLUSIONS: This study showed that a greater intake of a "Western
      diet" is associated with poorer SC and NSM, a "High sweet snacks and sugar
      sweetened drinks" intake is correlated with a lower SC, and high-carbohydrate
      food is related to elevated prevalences of abnormal TSM and PRM.

PMID- 26218803
TI  - Microbiome influences on allergy in mice and humans.
AB  - The microbiota plays a pivotal role in the development and calibration of host
      immunity. Over many millennia, finely balanced interactions between the
      microbiota and host tissue compartments have evolved, imparting metabolic
      advantages and protection against pathogens, while restricting deleterious immune
      responses against innocuous antigens. Perturbations in host-microbiota crosstalk
      at critical developmental windows in early life may underlie allergy and chronic
      inflammation. Although the microbiota's of the gut and skin have been extensively
      characterized, the lung microbiota has also, in recent years, received
      considerable attention. This ever-expanding field is pushing the boundaries of
      pulmonary research, with potential implications for novel strategies in the
      treatment and prevention of chronic lung diseases. In this article, we provide a
      summary of the development of the microbiota in early life, and describe the
      evidence from human and murine studies of how microbial dysbiosis in early life
      can alter the trajectory of immune development and provide the setting for
      allergic disorders in later life. 

PMID- 26218800
TI  - Enhancement of Antihyperalgesia by the Coadministration of N
      palmitoylethanolamide and Acetaminophen in Diabetic Rats.
AB  - Preclinical Research The objective of this study was to evaluate the
      pharmacological antihyperalgesic interaction between N-palmitoylethanolamide
      (PEA) and acetaminophen in diabetic rats using the formalin paw test.
      Streptozotocin (STZ)-induced diabetic rats received subcutaneous injections in
      the paw of PEA alone (1-100 MUg/paw) or acetaminophen alone (3-300 MUg/paw) 15
      min before formalin (0.5%) injection. The results revealed concentration
      dependent responses produced by PEA (EC50 = 7.19 +/- 0.7 MUg/paw) and
      acetaminophen (EC50 = 57.9 +/- 1.9 MUg/paw). Isobolographic analysis was used to
      evaluate the pharmacological interaction between the PEA + acetaminophen using
      the EC50 value and a fixed 1:1 ratio combination. The isobologram demonstrated
      that the combination investigated in this study produced a synergistic
      interaction; the experimental value (EC50 = 23.64 +/- 1.9 MUg/paw) was
      significantly smaller than those that resulted from theoretical calculations
      (EC50 = 32.56 MUg/paw). These results provide evidence that PEA in combination
      with acetaminophen could be useful for pain therapy in neuropathic diabetic
      patients.

PMID- 26218805
TI  - Aggregation-Induced Emission from Fluorophore-Quencher Dyads with Long-Lived
      Luminescence.
AB  - Aggregation-induced emission (AIE) is an important photophysical phenomenon in
      molecular materials and has found broad applications in optoelectronics,
      bioimaging, and chemosensing. Currently, the majority of reported AIE-active
      molecules are based on either propeller-shaped rotamers or donor-acceptor
      molecules with strong intramolecular charge-transfer states. Here, we report a
      new design motif, where a fluorophore is covalently tethered to a quencher, to
      expand the scope of AIE-active materials. The fluorophore-quencher dyad (FQD) is
      nonemissive in solutions due to photoinduced electron-transfer quenching but
      becomes luminescent in the solid state. The intrinsic emission lifetimes are
      found to be within the microseconds domain at both room and low temperatures. We
      performed single-crystal X-ray diffraction measurement for each of the FQDs as
      well as theoretical calculations to account for the possible origin of the long
      lived AIE. These FQDs represent a new class of AIE-active molecules with
      potential applications in organic optoelectronics. 

PMID- 26218801
TI  - Risk factors and biofilm detection on central venous catheters of patients
      attended at tertiary hospital.
AB  - AIM: To determinate the significance of risk factors with the presence of biofilm
      on catheters of patients attended at tertiary hospital cares. MATERIAL AND
      METHODS: A total of 126 patients were included, data collection by observing the
      handling of the CVC, clinical history and microbiological isolation methods of
      CVCs tips (Roll-plate, sonication and scanning electron microscopy) were
      evaluated. RESULTS: Certain factors, such as the lack of proper hand washing, the
      use of primary barriers and preparing medications in the same hospital service,
      showed an important relationship between biofilm formation in CVCs. The
      sonication method presented that most of the samples had isolation of
      multispecies 29 samples (64%); in contrast with the roll-plate method, just one
      sample (3%) was isolated. CONCLUSIONS: The importance of the strict aseptic
      techniques of insertion and of the handlings of CVC was highlighted, the failure
      of both techniques was related to the biofilm formation and was evidenced using
      the scanning electron microscopy. Since this tool is not available in most
      hospitals, we present the correlation of those evidences with other standard
      microbiological methods and risk factors, which are necessary for the sensible
      detection of the different steps of the biofilm formation on CVC and their
      correct interpretation with clinical evidences.

PMID- 26218799
TI  - Modified 2,4-diaryl-5H-indeno[1,2-b]pyridines with hydroxyl and chlorine moiety:
      Synthesis, anticancer activity, and structure-activity relationship study.
AB  - As a part of ongoing studies in developing novel anticancer agents, a series of
      modified 2,4-diaryl-5H-indeno[1,2-b]pyridines were designed, and synthesized by
      introducing hydroxyl and chlorine moieties. They were evaluated for topoisomerase
      inhibitory activity and cytotoxicity against HCT15, T47D, and HeLa cancer cell
      lines. This modification allowed us to demonstrate structure-activity
      relationship (SAR) study with respect to the non-substituted 2,4-diaryl-5H
      indeno[1,2-b]pyridines. Compounds (2, 3, 4, 5, 8, and 9) with meta or para
      hydroxyl group on 2 or 4-phenyl ring have enhanced topo I and II inhibitory
      activity and cytotoxicity. However, additional substitution of chlorine group on
      furyl or thienyl ring (11, 12, 14, 16-18) generally reduced topo I and II
      inhibitory activity but improved cytotoxicity. The observation of cytotoxic
      properties and SAR study according to the position of hydroxyl and chlorine group
      will provide valuable insight for further study of development of novel
      anticancer agents with related scaffolds. 

PMID- 26218808
TI  - From the Editors.

PMID- 26218809
TI  - Increasing Morbidity in the Pregnant Population in the United States.

PMID- 26218797
TI  - A Compartmental Comparison of Major Lipid Species in a Coral-Symbiodinium
      Endosymbiosis: Evidence that the Coral Host Regulates Lipogenesis of Its
      Cytosolic Lipid Bodies.
AB  - The lipid body (LB) formation in the host coral gastrodermal cell cytoplasm is a
      hallmark of the coral-Symbiodinium endosymbiosis, and such lipid-based entities
      are not found in endosymbiont-free cnidarian cells. Therefore, the elucidation of
      lipogenesis regulation in LBs and how it is related to the lipid metabolism of
      the host and endosymbiont could provide direct insight to understand the
      symbiosis mechanism. Herein, the lipid composition of host cells of the stony
      coral Euphyllia glabrescens, as well as that of their cytoplasmic LBs and in
      hospite Symbiodinium populations, was examined by high performance liquid
      chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS), and six
      major lipid species were identified: wax esters, sterol esters, triacylglycerols,
      cholesterols, free fatty acids, and phospholipids. Their concentrations differed
      significantly between host coral cells, LBs, and Symbiodinium, suggesting
      compartmental regulation. WE were only present in the host coral and were
      particularly highly concentrated in LBs. Amongst the four species of WE, the
      monoene R = C18:1/R = C16 was found to be LB-specific and was not present in the
      host gastrodermal cell cytoplasm. Furthermore, the acyl pool profiles of the
      individual LB lipid species were more similar, but not equal to, those of the
      host gastrodermal cells in which they were located, indicating partially
      autonomous lipid metabolism in these LBs. Nevertheless, given the overall
      similarity in the host gastrodermal cell and LB lipid profiles, these data
      suggest that a significant portion of the LB lipids may be of host coral origin.
      Finally, lipid profiles of the in hospite Symbiodinium populations were
      significantly distinct from those of the cultured Symbiodinium, potentially
      suggesting a host regulation effect that may be fundamental to lipid metabolism
      in endosymbiotic associations involving clade C Symbiodinium. 

PMID- 26218798
TI  - Characterization of the nuclear matrix targeting sequence (NMTS) of the BPV1
      E8/E2 protein--the shortest known NMTS.
AB  - Technological advantages in sequencing and proteomics have revealed the
      remarkable diversity of alternative protein isoforms. Typically, the localization
      and functions of these isoforms are unknown and cannot be predicted. Also the
      localization signals leading to particular subnuclear compartments have not been
      identified and thus, predicting alternative functions due to alternative
      subnuclear localization is limited only to very few subnuclear compartments.
      Knowledge of the localization and function of alternative protein isoforms allows
      for a greater understanding of cellular complexity. In this article, we
      characterize a short and well-defined signal targeting the bovine papillomavirus
      type 1 E8/E2 protein to the nuclear matrix. The targeting signal comprises the
      peptide coded by E8 ORF, which is spliced together with part of the E2 ORF to
      generate the E8/E2 mRNA. Localization to the nuclear matrix correlates well with
      the transcription repression activities of E8/E2; a single point mutation directs
      the E8/E2 protein into the nucleoplasm, and transcription repression activity is
      lost. Our data prove that adding as few as ~10 amino acids by alternative
      transcription/alternative splicing drastically alters the function and subnuclear
      localization of proteins. To our knowledge, E8 is the shortest known nuclear
      matrix targeting signal. 

PMID- 26218810
TI  - Initiating Care for the Extremely Low Gestational Age Infant.

PMID- 26218811
TI  - Listen Carefully: Implementing Intermittent Auscultation Into Routine Practice.

PMID- 26218806
TI  - The ATPase activity of the mycobacterial plasma membrane is inhibited by the LL37
      analogous peptide LLAP.
AB  - The emergence of multidrug-resistant Mycobacterium tuberculosis strains has led
      to the development of new antituberculous agents. In this context, antimicrobial
      targeting proteins to the cell membrane are interesting due to the avoidance of
      the plasma membrane permeation. Through this study, the antimicrobial activity,
      cellular toxicity, as well as the effect on the mycobacterial cell membrane
      ATPase activity of a cathelicidin-analogous peptide were assessed. By using
      bioinformatics analyses, a 15 amino acid LL37-analogous peptide called LLAP,
      which has the amino acid sequence: GRKSAKKIGKRAKRI, was designed to improve its
      helical structure and antibacterial activity compared to the native sequence. The
      LLAP peptide was synthesized, purified by RP-HPLC and its structural
      characteristics were determined by MALDI-TOF MS and circular dichroism. Compared
      to the native amino acid sequence, the minimum inhibitory concentration and
      cytotoxic activity of LLAP were 4.0 and 5.6-fold lower, respectively. In
      addition, the hemolytic activity of LLAP was lower than 1.1% and the cytotoxic
      activity of peptides was similar for both peptides. Interestingly, the LLAP
      peptide displayed approximately 50% inhibition of basal ATPase activity of the
      mycobacterial plasma membrane, which could in turn be associated with the
      impaired cell viability. The results suggest that LLAP could be considered as
      potential antimycobacterial compounds against cell membrane targeting ATPases.
      However, this antimycobacterial activity can be improved. It is expected further
      applications to be found for other antimicrobial peptides families based on the
      implemented methodology. 

PMID- 26218807
TI  - Pancreatic polypeptide responses to isoglycemic oral and intravenous glucose in
      humans with and without intact vagal innervation.
AB  - Secretion of pancreatic polypeptide (PP) from the pancreatic PP cells is
      controlled partly by vagal mechanisms. Release is stimulated by cephalic
      stimulation and enteral but not parenteral nutrients. Ambient glucose levels
      modulate circulating PP levels as hypoglycemia stimulates while hyperglycemia
      inhibits secretion. The glucose sensing mechanism has yet to be determined but
      may involve a vagal pathway. To investigate the role of enteral stimuli with or
      without intact vagal innervation, while controlling for the glucose excursion
      caused by the OGTT, we measured PP plasma levels by an in-house radioimmunoassay
      in truncally vagotomized (n=15) and control individuals (n=10). All participants
      were studied by a 50-g oral glucose tolerance test (OGTT) with or without
      dipeptidyl peptidase 4 (DPP-4) inhibition (DPP-4i) and a subsequent isoglycemic
      intravenous glucose infusion (IGII). We included measurements from the DPP-4i day
      to determine the potential effect of DPP-4-cleaved peptides on PP secretion. In
      both vagotomized and controls, oral glucose elicited PP secretion. In controls,
      but not in the vagotomized participants, intravenous glucose significantly
      inhibited PP secretion suggesting a vagal glucose sensing mechanism dependent on
      intact vagal innervation. DPP-4i did not alter PP secretion in either group. 

PMID- 26218804
TI  - Reduction of Salmonella Enteritidis in the spleens of hens by bacterins that vary
      in fimbrial protein SefD.
AB  - The objective of this research was to determine whether variation in the presence
      of fimbrial protein SefD would impact efficacy of bacterins as measured by
      recovery of Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) from
      the spleens of hens. Two bacterins were prepared that varied in SefD content.
      Also, two adjuvants were tested, namely, water-in-oil and aluminum hydroxide gel
      (alum). Control groups for both adjuvant preparations included infected
      nonvaccinated hens and uninfected nonvaccinated hens. At 21 days postinfection,
      Salmonella Enteritidis was recovered from 69.7%, 53.1%, and 86.0% from the
      spleens of all hens vaccinated with bacterins lacking SefD, bacterins that
      included SefD, and infected nonvaccinated control hens, respectively. No
      Salmonella was recovered from uninfected nonvaccinates. Results from individual
      trials showed that both bacterins reduced positive spleens, but that the one with
      SefD was more efficacious. Alum adjuvant had fewer side effects on hens and egg
      production as compared to water-in-oil. However, adjuvant did not change the
      relative recovery of Salmonella Enteritidis from spleens. These results suggest
      that SefD is a promising target antigen for improving the efficacy of
      immunotherapy in hens, and is intended to reduce Salmonella Enteritidis in the
      food supply. 

PMID- 26218812
TI  - Internet Resources.

PMID- 26218815
TI  - Cardiomyopathy During Pregnancy.
AB  - Cardiomyopathy is an acquired cardiac disorder that, although rare, accounts for
      a rising proportion of reported pregnancy-related deaths in the United States.
      During pregnancy, cardiomyopathy may be divided into 2 groups. The first group is
      peripartum cardiomyopathy; the second group is stratified according to 3
      classically defined pathophysiologic presentations: hypertrophic, dilated, or
      restrictive. Within this second group, the cardiomyopathy can be either
      idiopathic or due to a specific identified cause. This disorder poses significant
      risks of morbidity and/or mortality to the pregnant woman and fetus/neonate. This
      article describes types of cardiomyopathy during pregnancy, perinatal risks, and
      general management principles with a focus on intrapartum care. Hemodynamic and
      oxygen transport data are presented to illustrate interpretation of patient
      assessment findings and the effects of interventions for abnormal maternal and
      fetal findings. 

PMID- 26218816
TI  - Multisystem Effects of Hypertensive Disorders of Pregnancy: A Comprehensive
      Review.
AB  - Hypertension predisposes the woman and fetus to adverse outcomes during the
      pregnancy and postpartum. The risk for maternal complications and neonatal
      morbidity associated with the necessity of preterm birth extends beyond the
      postpartum and postnatal period. A comprehensive review of the multisystem
      effects of hypertensive disorders and underlying pathophysiology is provided to
      support the role of prompt identification of and management of acute
      complications of hypertension. 

PMID- 26218817
TI  - Understanding the Biologic Therapies of Probiotics, Prebiotics, and Synbiotics:
      Exploring Current Evidence for Use in Premature Infants for the Prevention of
      Necrotizing Enterocolitis.
AB  - Necrotizing enterocolitis remains a significant cause of morbidity and mortality
      in very low-birth-weight infants (<1500 g), with current preventive strategies
      unclear. Scientific evidence has recently emerged, suggesting that probiotics,
      prebiotics, and synbiotics may effectively and safely alter the premature
      intestinal microbiota, enhancing a deficient innate immune response and maturing
      the intestinal barrier to prevent necrotizing enterocolitis development.
      Currently, formal recommendations do not support routine use of these dietary
      supplementations for premature infants. Here, we examine how probiotic,
      prebiotic, and synbiotic preparations physiologically alter the underdeveloped
      intestinal microbial environment to potentially reduce necrotizing enterocolitis
      incidence and discuss current evidence that has examined safety and efficacy
      factors potentially supporting routine use among the premature infant population.

PMID- 26218813
TI  - Maternal Morbidity and Mortality: Identifying Opportunities to Improve Clinical
      Outcomes.
AB  - A better understanding of why women die during pregnancy, childbirth, or
      postpartum offers valuable insight into strategies aimed at preventing maternal
      deaths and arresting the progression in the severity of a complication. The rate
      of severe maternal morbidity and maternal mortality in the United States has been
      trending upward in recent years and has garnered national attention with
      concentration on bolstering reviews of maternal deaths and implementing patient
      safety initiatives. The obstetric nurse is in a unique position to improve
      maternal outcomes through the anticipation, recognition, and communication of the
      early warning signs of impending deterioration in maternal condition. Presented
      in the context of the conceptual model of Stephen Covey's Circle of Influence,
      the professional nurse can proactively influence maternal outcomes directly, with
      actions defined by the scope of professional nursing practice or indirectly
      through professional interactions with others. Advancing one's education,
      knowledge, and technical skills broadens the influential capacity. 

PMID- 26218814
TI  - Obstetric Sepsis: Focus on the 3-Hour Bundle.
AB  - Early recognition and treatment of sepsis are key to decreasing maternal and
      fetal morbidity and mortality. Timing is critical, and early intervention is
      associated with improved outcomes. The perinatal provider is in a unique position
      to identify risk factors, perform assessments, and implement the first 3 hours of
      the sepsis bundle. Early detection and management combined with careful
      assessment can assist in providing evidence-based care and moving the patient to
      a higher level of care when warranted. 

PMID- 26218819
TI  - Ensuring Quality in the NICU: Translating Research Into Appropriate Clinical
      Care.
AB  - Since the Institute of Medicine's landmark report To Err Is Human, extensive
      efforts to improve patient safety have been undertaken. However, wide-scale
      improvement has been limited, sporadic, and inconsistent. Implementation of
      evidence-based interventions remains a challenge, resulting in unwarranted
      variations in care. Three main categories of problems in healthcare delivery are
      defined as overuse, underuse, and misuse of medical services, resulting in
      inappropriate care, inefficiencies, and poor quality. Although broad
      acknowledgement that these categories of quality problems exist, there are
      limited standards for measuring their overall impact. This article aims to
      discuss the important role of implementation science in advancing evidence-based
      practice, using neonatal therapeutic hypothermia for the treatment of hypoxic
      ischemic encephalopathy as an exemplar for examining appropriateness of care. 

PMID- 26218825
TI  - A Simple and Easily Available Nostril Retainer Using a Syringe.

PMID- 26218820
TI  - Have You Met GINA?

PMID- 26218818
TI  - Effect of Breast-Feeding and Maternal Holding in Relieving Painful Responses in
      Full-Term Neonates: A Randomized Clinical Trial.
AB  - This randomized clinical trial was conducted to determine the efficacy of breast
      feeding with maternal holding as compared with maternal holding without breast
      feeding in relieving painful responses during heel lance blood drawing in full
      term neonates. A convenience sample of 128 full-term newborn infants, in their
      fourth to sixth days of life, undergoing heel lance blood drawing for screening
      of hypothyroidism were included in the study. The neonates were randomly assigned
      into 2 equivalent groups. During heel lance blood drawing for infants, they
      either breast-fed with maternal holding (group I) or were held in their mother's
      lap without breast-feeding (group II). The painful responses were assessed
      simultaneously by 2 neonatal nurses blinded to the purpose of the study. Outcome
      measures for painful responses of the full-term neonates were evaluated with the
      Premature Infant Pain Profile scale. Independent t test showed significant
      differences in Premature Infant Pain Profile scale scores among the 2 groups (t =
      -8.447, P = .000). Pain scores were significantly lower among infants who were
      breast-fed in addition to maternal holding. Evidence from this study indicates
      that the combination of breast-feeding with maternal holding reduces painful
      responses of full-term infants during heel lance blood drawing. 

PMID- 26218823
TI  - Stereoselective Synthesis of Substituted Tetrahydropyrans and Isochromans by
      Cyclization of Phenylseleno Alcohols.
AB  - A selenium-mediated strategy for the stereoselective synthesis of substituted
      tetrahydropyrans and isochromans has been developed starting from delta
      phenylseleno ketones. After enantioselective reduction, the chiral nonracemic
      phenylseleno alcohols were oxidized to the corresponding selenones, which
      underwent an effcient 6-exo-tet ring-closure reaction. 

PMID- 26218826
TI  - Cryolipolysis for Targeted Fat Reduction and Improved Appearance of the Enlarged
      Male Breast.
AB  - BACKGROUND: Pseudogynecomastia refers to benign male breast enlargement due to
      excess subareolar fat. Standard treatment is surgical excision under general
      anesthesia, liposuction, or a combination of both. OBJECTIVE: The safety and
      efficacy of cryolipolysis was investigated for nonsurgical treatment of
      pseudogynecomastia. METHODS AND MATERIALS: Enrollment consisted of 21 males with
      pseudogynecomastia. Subjects received a first treatment consisting of a 60-minute
      cryolipolysis cycle, followed by a two-minute massage, and a second 60-minute
      cycle with 50% treatment area overlap. At 60 days of follow-up, subjects received
      a second 60-minute treatment. Safety was evaluated by monitoring side effects and
      adverse events. Efficacy was assessed by ultrasound, clinical photographs, and
      subject surveys. RESULTS: Surveys revealed that 95% of subjects reported improved
      visual appearance and 89% reported reduced embarrassment associated with
      pseudogynecomastia. Ultrasound showed mean fat layer reduction of 1.6 +/- 1.2 mm.
      Blinded reviewers correctly identified 82% of baseline photographs. Side effects
      included mild discomfort during treatment and transient paresthesia and
      tenderness. One case of paradoxical hyperplasia (PH) occurred but likelihood of
      PH in the male breast is not believed to be greater than in any other treatment
      area. CONCLUSION: This study demonstrated feasibility of cryolipolysis for safe,
      effective, and well-tolerated nonsurgical treatment of pseudogynecomastia.

PMID- 26218828
TI  - Excitonic condensation in systems of strongly correlated electrons.
AB  - The idea of exciton condensation in solids was introduced in the 1960s with the
      analogy of superconductivity in mind. While exciton supercurrents have been
      realised only in artificial quantum-well structures so far, the application of
      the concept of excitonic condensation to bulk solids leads to a rich spectrum of
      thermodynamic phases with diverse physical properties. In this review we discuss
      recent developments in the theory of exciton condensation in systems described by
      Hubbard-type models. In particular, we focus on the connections to their various
      strong-coupling limits that have been studied in other contexts, e.g. cold atoms
      physics. One of our goals is to provide a 'dictionary' that would allow the
      reader to efficiently combine results obtained in these different fields. 

PMID- 26218827
TI  - The human medial amygdala: structure, diversity, and complexity of dendritic
      spines.
AB  - The medial nucleus of the amygdala (Me) is a component of the neural circuit for
      the interpretation of multimodal sensory stimuli and the elaboration of emotions
      and social behaviors in primates. We studied the presence, distribution, diverse
      shape, and connectivity of dendritic spines in the human Me of adult postmortem
      men. Data were obtained from the five types of multipolar neurons found in the Me
      using an adapted Golgi method and light microscopy, the carbocyanine DiI
      fluorescent dye and confocal microscopy, and transmission electron microscopy.
      Three-dimensional reconstruction of spines showed a continuum of shapes and
      sizes, with the spines either lying isolated or forming clusters. These dendritic
      spines were classified as stubby/wide, thin, mushroom-like, ramified or with an
      atypical morphology including intermediate shapes, double spines, and thorny
      excrescences. Pleomorphic spines were found from proximal to distal dendritic
      branches suggesting potential differences for synaptic processing, strength, and
      plasticity in the Me neurons. Furthermore, the human Me has large and thin spines
      with a gemmule appearance, spinules, and filopodium. The ultrastructural data
      showed dendritic spines forming monosynaptic or multisynaptic contacts at the
      spine head and neck, and with asymmetric or symmetric characteristics. Additional
      findings included en passant, reciprocal, and serial synapses in the Me. Complex
      long-necked thin spines were observed in this subcortical area. These new data
      reveal the diversity of the dendritic spines in the human Me likely involved with
      the integration and processing of local synaptic inputs and with functional
      implications in physiological and various neuropathological conditions. 

PMID- 26218829
TI  - Longitudinal three-dimensional-T2WI-SPACE study on wallerian degeneration in cat
      corticospinal tract and underlying pathology changes.
AB  - PURPOSE: To investigate the feasibility of T2W-SPACE technique in early detection
      of WD, the signal evolutions of degenerated corticospinal tract (CST) on T2W
      SPACE, and their underlying pathological changes. MATERIALS AND METHODS: The WD
      model of the CST was established in 23 cats through excision of cortical origins
      of the tract. Eight cats were scanned with the T2W-SPACE technique at 8
      sequential time points, i.e. 0 (before modeling), 2, 4, 6, 8, 10, 20 and 30 days
      after modeling, and then they were pathologically examined. The remaining 15 cats
      (3 per group) also underwent pathological examination at 2, 4, 6, 10 and 20 days
      after modeling, respectively. The ratios of T2 signal intensity (rT2s) between
      the affected and unaffected sides of CST were analyzed. RESULTS: During the first
      4 days, SPACE could not detect any significant changes of the affected CST,
      although axonal degeneration was pathologically observed at the second day. From
      6 to 10 days, the rT2s decreased monotonously, which is corresponded to
      histological findings of myelin degeneration and phagocyte proliferation. From 10
      to 20 days, rT2s kept relatively stable at a low level and started to recover
      after that; the pathological changes of this period was characterized by marked
      phagocytizing activities. CONCLUSION: SPACE technique can detect Wallerian
      degeneration at an early stage, and the signal evolution is consistent with the
      pathological processes.

PMID- 26218830
TI  - Bias and precision of measures of survival gain from right-censored data.
AB  - In cost-effectiveness analyses of drugs or health technologies, estimates of life
      years saved or quality-adjusted life years saved are required. Randomised
      controlled trials can provide an estimate of the average treatment effect; for
      survival data, the treatment effect is the difference in mean survival. However,
      typically not all patients will have reached the endpoint of interest at the
      close-out of a trial, making it difficult to estimate the difference in mean
      survival. In this situation, it is common to report the more readily estimable
      difference in median survival. Alternative approaches to estimating the mean have
      also been proposed. We conducted a simulation study to investigate the bias and
      precision of the three most commonly used sample measures of absolute survival
      gain--difference in median, restricted mean and extended mean survival--when used
      as estimates of the true mean difference, under different censoring proportions,
      while assuming a range of survival patterns, represented by Weibull survival
      distributions with constant, increasing and decreasing hazards. Our study showed
      that the three commonly used methods tended to underestimate the true treatment
      effect; consequently, the incremental cost-effectiveness ratio (ICER) would be
      overestimated. Of the three methods, the least biased is the extended mean
      survival, which perhaps should be used as the point estimate of the treatment
      effect to be inputted into the ICER, while the other two approaches could be used
      in sensitivity analyses. More work on the trade-offs between simple extrapolation
      using the exponential distribution and more complicated extrapolation using other
      methods would be valuable.

PMID- 26218831
TI  - Blue Marble Health Redux: Neglected Tropical Diseases and Human Development in
      the Group of 20 (G20) Nations and Nigeria.

PMID- 26218833
TI  - Correction: Identification of Relevant Phytochemical Constituents for
      Characterization and Authentication of Tomatoes by General Linear Model Linked to
      Automatic Interaction Detection (GLM-AID) and Artificial Neural Network Models
      (ANNs).

PMID- 26218832
TI  - An Effective Approach for Clustering InhA Molecular Dynamics Trajectory Using
      Substrate-Binding Cavity Features.
AB  - Protein receptor conformations, obtained from molecular dynamics (MD)
      simulations, have become a promising treatment of its explicit flexibility in
      molecular docking experiments applied to drug discovery and development. However,
      incorporating the entire ensemble of MD conformations in docking experiments to
      screen large candidate compound libraries is currently an unfeasible task.
      Clustering algorithms have been widely used as a means to reduce such ensembles
      to a manageable size. Most studies investigate different algorithms using
      pairwise Root-Mean Square Deviation (RMSD) values for all, or part of the MD
      conformations. Nevertheless, the RMSD only may not be the most appropriate gauge
      to cluster conformations when the target receptor has a plastic active site,
      since they are influenced by changes that occur on other parts of the structure.
      Hence, we have applied two partitioning methods (k-means and k-medoids) and four
      agglomerative hierarchical methods (Complete linkage, Ward's, Unweighted Pair
      Group Method and Weighted Pair Group Method) to analyze and compare the quality
      of partitions between a data set composed of properties from an enzyme receptor
      substrate-binding cavity and two data sets created using different RMSD
      approaches. Ensembles of representative MD conformations were generated by
      selecting a medoid of each group from all partitions analyzed. We investigated
      the performance of our new method for evaluating binding conformation of drug
      candidates to the InhA enzyme, which were performed by cross-docking experiments
      between a 20 ns MD trajectory and 20 different ligands. Statistical analyses
      showed that the novel ensemble, which is represented by only 0.48% of the MD
      conformations, was able to reproduce 75% of all dynamic behaviors within the
      binding cavity for the docking experiments performed. Moreover, this new approach
      not only outperforms the other two RMSD-clustering solutions, but it also shows
      to be a promising strategy to distill biologically relevant information from MD
      trajectories, especially for docking purposes. 

PMID- 26218834
TI  - Interleukin-6 inhibits adrenal androgen release from bovine adrenal zona
      reticularis cells by inhibiting the expression of steroidogenic proteins.
AB  - Interleukin-6 (IL-6) is secreted by adrenocortical cells and modifies cortisol
      secretion. In this study, the effects of IL-6 on adrenal androgen release were
      investigated. The zona reticularis (ZR) was generally isolated from bovine
      adrenal glands by dissection. In select experiments, the intact adrenal cortex
      (ie, all 3 adrenocortical zones) was dissected from the adrenal glands. For
      androgen release experiments, ZR and intact adrenocortical cubes were dispersed
      into isolated cells, the cells cultured and exposed to IL-6 and/or
      adrenocorticotropic hormone (ACTH), and androgen release determined by
      radioimmunoassay. Basal and ACTH-stimulated androgen release from the ZR was
      inhibited by IL-6 in a concentration-dependent (10-1000 pg/mL) and time-dependent
      (4-24 h) manner (P < 0.01 by 1-way analysis of variance and the Bonferroni test).
      In contrast, IL-6 increased basal and ACTH-stimulated androgen release from mixed
      adrenocortical cells (P < 0.01). The mechanism of IL-6 inhibition of androgen
      release was investigated by exposing ZR strips to IL-6 and measuring the
      expression of the messenger RNA (mRNA) and protein of steroidogenic factors.
      Basal and ACTH-stimulated expression of the mRNA and protein for steroidogenic
      acute regulatory protein, cholesterol side chain cleavage enzyme, 3-beta
      hydroxysteroid dehydrogenase type 2, steroid 17-alpha-hydroxylase/17,20
      lyase/17,20 desmolase, and the nuclear factor steroidogenic factor 1 (SF-1), that
      stimulates steroidogenesis, were decreased by IL-6 (P < 0.01). In contrast IL-6
      increased the mRNA and protein for dosage-sensitive sex reversal, adrenal
      hypoplasia critical region, on chromosome X, gene 1 (DAX-1), a nuclear factor
      that inhibits steroidogenesis (P < 0.01). In summary, IL-6 decreased androgen
      release and the expression of steroidogenic factors in the ZR, and this decrease
      may be mediated in part through increasing DAX-1 and decreasing SF-1. 

PMID- 26218835
TI  - Dense, shape-optimized posterior 32-channel coil for submillimeter functional
      imaging of visual cortex at 3T.
AB  - PURPOSE: Functional neuroimaging of small cortical patches such as columns is
      essential for testing computational models of vision, but imaging from cortical
      columns at conventional 3T fields is exceedingly difficult. By targeting the
      visual cortex exclusively, we tested whether combined optimization of shape, coil
      placement, and electronics would yield the necessary gains in signal-to-noise
      ratio (SNR) for submillimeter visual cortex functional MRI (fMRI). METHOD: We
      optimized the shape of the housing to a population-averaged atlas. The shape was
      comfortable without cushions and resulted in the maximally proximal placement of
      the coil elements. By using small wire loops with the least number of solder
      joints, we were able to maximize the Q factor of the individual elements.
      Finally, by planning the placement of the coils using the brain atlas, we were
      able to target the arrangement of the coil elements to the extent of the visual
      cortex. RESULTS: The combined optimizations led to as much as two-fold SNR gain
      compared with a whole-head 32-channel coil. This gain was reflected in temporal
      SNR as well and enabled fMRI mapping at 0.75 mm resolutions using a conventional
      GRAPPA-accelerated gradient echo echo planar imaging. CONCLUSION: Integrated
      optimization of shape, electronics, and element placement can lead to large gains
      in SNR and empower submillimeter fMRI at 3T. Magn Reson Med 76:321-328, 2016. (c)
      2015 Wiley Periodicals, Inc.

PMID- 26218836
TI  - Field Deployable Chemical Redox Probe for Quantitative Characterization of
      Carboxymethylcellulose Modified Nano Zerovalent Iron.
AB  - Nano zerovalent iron synthesized with carboxymethylcelluose (CMC-nZVI) is among
      the leading formulations of nZVI currently used for in situ groundwater
      remediation. The main advantage of CMC-nZVI is that it forms stable suspensions,
      which are relatively mobile in porous media. Rapid contaminant reduction by CMC
      nZVI is well documented, but the fate of the CMC-nZVI (including "aging" and
      "reductant demand") is not well characterized. Improved understanding of CMC-nZVI
      fate requires methods with greater specificity for Fe(0), less vulnerability to
      sampling/recovery artifacts, and more practical application in the field. These
      criteria can be met with a simple and specific colorimetric approach using indigo
      5,5'-disulfonate (I2S) as a chemical redox probe (CRP). The measured
      stoichiometric ratio for reaction between I2S and nZVI is 1.45 +/- 0.03,
      suggesting complete oxidation of nZVI to Fe(III) species. However, near pH 7,
      reduction of I2S is diagnostic for Fe(0), because aqueous Fe(II) reduces I2S much
      more slowly than Fe(0). At that pH, adding Fe(II) increased I2S reduction rates
      by Fe(0), consistent with depassivation of nZVI, but did not affect the
      stoichiometry. Using the I2S assay to quantify changes in the Fe(0) content of
      CMC-nZVI, the rate of Fe(0) oxidation by water was found to be orders of
      magnitude faster than previously reported values for other types of nZVI. 

PMID- 26218841
TI  - Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of
      Mycobacterium tuberculosis in human macrophages.
AB  - LL-37 is a human antimicrobial peptide (AMP) of the cathelicidin family with
      multiple activities including a mediator of vitamin D-induced autophagy in human
      macrophages, resulting in intracellular killing of Mycobacterium tuberculosis
      (Mtb). In a previous trial in healthy volunteers, we have shown that LL-37
      expression and subsequent Mtb-killing can be further enhanced by 4-phenylbutyrate
      (PBA), also an inducer of LL-37 expression. Here, we explore a potential
      mechanism(s) behind PBA and LL-37-induced autophagy and intracellular killing of
      Mtb. Mtb infection of macrophages downregulated the expression of both the CAMP
      transcript and LL-37 peptide as well as certain autophagy-related genes (BECN1
      and ATG5) at both the mRNA and protein levels. In addition, activation of LC3-II
      in primary macrophages and THP-1 cells was not detected. PBA and the active form
      of vitamin D3 (1,25[OH]2D3), separately or particularly in combination, were able
      to overcome Mtb-induced suppression of LL-37 expression. Notably, reactivation of
      autophagy occurred by stimulation of macrophages with PBA and promoted
      colocalization of LL-37 and LC3-II in autophagosomes. Importantly, PBA treatment
      failed to induce autophagy in Mtb-infected THP-1 cells, when the expression of LL
      37 was silenced. However, PBA-induced autophagy was restored when the LL-37
      knockdown cells were supplemented with synthetic LL-37. Interestingly, we have
      found that LL-37-induced autophagy was mediated via P2RX7 receptor followed by
      enhanced cytosolic free Ca(2+), and activation of AMPK and PtdIns3K pathways.
      Altogether, these results suggest a novel activity for PBA as an inducer of
      autophagy, which is LL-37-dependent and promotes intracellular killing of Mtb in
      human macrophages. 

PMID- 26218842
TI  - Is 9 louder than 1? Audiovisual cross-modal interactions between number magnitude
      and judged sound loudness.
AB  - The cross-modal impact of number magnitude (i.e. Arabic digits) on perceived
      sound loudness was examined. Participants compared a target sound's intensity
      level against a previously heard reference sound (which they judged as quieter or
      louder). Paired with each target sound was a task irrelevant Arabic digit that
      varied in magnitude, being either small (1, 2, 3) or large (7, 8, 9). The degree
      to which the sound and the digit were synchronized was manipulated, with the
      digit and sound occurring simultaneously in Experiment 1, and the digit preceding
      the sound in Experiment 2. Firstly, when target sounds and digits occurred
      simultaneously, sounds paired with large digits were categorized as loud more
      frequently than sounds paired with small digits. Secondly, when the events were
      separated, number magnitude ceased to bias sound intensity judgments. In
      Experiment 3, the events were still separated, however the participants held the
      number in short-term memory. In this instance the bias returned. 

PMID- 26218844
TI  - Selective C-H and C-C Bond Activation: Electronic Regimes as a Tool for Designing
      d(10) MLn Catalysts.
AB  - We wish to understand how a transition-metal catalyst can be rationally designed
      so as to selectively activate one particular bond in a substrate, herein, C-H and
      C-C bonds in ethane. To this end, we quantum chemically analyzed the activity and
      selectivity of a large series of model catalysts towards ethane and, for
      comparison, methane, by using the activation strain model and quantitative
      molecular orbital theory. The model catalysts comprise d(10) MLn complexes with
      coordination numbers n=0, 1, and 2; metal centers M=Co(-), Rh(-), Ir(-), Ni, Pd,
      Pt, Cu(+), Ag(+), and Au(+); and ligands L=NH3, PH3, and CO. Our analyses reveal
      that rather subtle electronic differences between bonds can be exploited to
      induce a lower barrier for activating one or the other, depending, among other
      factors, on the catalysts electronic regime (i.e., s-regime versus d-regime
      catalysts). Interestingly, the concepts and design principles emerging from this
      work can also be applied to the more challenging problem of differentiating
      between activation of the C-H bonds in ethane versus those in methane.

PMID- 26218843
TI  - Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV
      Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss
      HIV Cohort Study.
AB  - BACKGROUND: Ribavirin (RBV) is an essential component of most current hepatitis C
      (HCV) treatment regimens and still standard of care in the combination with
      pegylated interferon (pegIFN) to treat chronic HCV in resource limited settings.
      Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV
      concentration correlates with sustained virological response (SVR). METHODS: We
      included 262 HCV treatment naive HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS)
      participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with
      HCV genotype (GT) 1/4, and 128 with GT 2/3 infections. RBV levels were measured
      retrospectively in stored plasma samples obtained between HCV treatment week 4
      and end of therapy. Uni- and multivariable logistic regression analyses were used
      to evaluate the association between RBV concentration and SVR in GT 1/4 and GT
      2/3 infections. The analyses were repeated stratified by treatment phase (week 4
      12, 13-24, >24) and IL28B genotype (CC versus CT/TT). RESULTS: SVR rates were
      35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration
      was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly
      across treatment phases. Patients with SVR had similar RBV concentrations
      compared to patients without SVR in both HCV genotype groups. SVR was not
      associated with RBV levels >=2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94
      [0.78-4.80]) and >=2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73]),
      regardless of treatment phase, and IL28B genotype. CONCLUSION: In HIV/HCV
      coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV
      concentrations does not enhance the chance of HCV cure, regardless of HCV
      genotype, treatment phase and IL28B genotype.

PMID- 26218845
TI  - Influence of galacto-oligosaccharide mixture (B-GOS) on gut microbiota, immune
      parameters and metabonomics in elderly persons.
AB  - It is recognised that ageing induces various changes to the human colonic
      microbiota. Most relevant is a reduction in bifidobacteria, which is a health
      positive genus. Prebiotics, such as galacto-oligosaccharides (GOS), are dietary
      ingredients that selectively fortify beneficial gut microbial groups. Therefore,
      they have the potential to reverse the age-related decline in bifidobacteria and
      modulate associated health parameters. We assessed the effect of GOS mixture
      (Bimuno (B-GOS)) on gut microbiota, markers of immune function and metabolites in
      forty elderly (age 65-80 years) volunteers in a randomised, double-blind, placebo
      (maltodextrin)-controlled, cross-over study. The intervention periods consisted
      of 10 weeks with daily doses of 5.5 g/d with a 4-week washout period in between.
      Blood and faecal samples were collected for the analyses of faecal bacterial
      populations and immune and metabolic biomarkers. B-GOS consumption led to
      significant increases in bacteroides and bifidobacteria, the latter correlating
      with increased lactic acid in faecal waters. Higher IL-10, IL-8, natural killer
      cell activity and C-reactive protein and lower IL-1beta were also observed.
      Administration of B-GOS to elderly volunteers may be useful in positively
      affecting the microbiota and some markers of immune function associated with
      ageing.

PMID- 26218846
TI  - The Gametocytes of Leucocytozoon sabrazesi Infect Chicken Thrombocytes, Not Other
      Blood Cells.
AB  - Leucocytozoon parasites infect a large number of avian hosts, including domestic
      chicken, and cause significant economical loss to the poultry industry. Although
      the transmission stages of the parasites were observed in avian blood cells more
      than a century ago, the specific host cell type(s) that the gametocytes infect
      remain uncertain. Because all the avian blood cells, including red blood cells
      (RBCs), are nucleated, and the developing parasites dramatically change the
      morphology of the infected host cells, it has been difficult to identify
      Leucocytozoon infected host cell(s). Here we use cell-type specific antibodies to
      investigate the identities of the host cells infected by Leucocytozoon sabrazesi
      gametocytes. Anti-RBC antibodies stained RBCs membrane strongly, but not the
      parasite-infected cells, ruling out the possibility of RBCs being the infected
      host cells. Antibodies recognizing various leukocytes including heterophils,
      monocytes, lymphocytes, and macrophages did not stain the infected cells either.
      Antisera raised against a peptide of the parasite cytochrome B (CYTB) stained
      parasite-infected cells and some leukocytes, particularly cells with a single
      round nucleus as well as clear/pale cytoplasm suggestive of thrombocytes.
      Finally, a monoclonal antibody known to specifically bind chicken thrombocytes
      also stained the infected cells, confirming that L. sabrazesi gametocytes develop
      within chicken thrombocytes. The identification of L. sabrazesi infected host
      cell solves a long unresolved puzzle and provides important information for
      studying parasite invasion of host cells and for developing reagents to interrupt
      parasite transmission. 

PMID- 26218847
TI  - Hedge Scope Detection in Biomedical Texts: An Effective Dependency-Based Method.
AB  - Hedge detection is used to distinguish uncertain information from facts, which is
      of essential importance in biomedical information extraction. The task of hedge
      detection is often divided into two subtasks: detecting uncertain cues and their
      linguistic scope. Hedge scope is a sequence of tokens including the hedge cue in
      a sentence. Previous hedge scope detection methods usually take all tokens in a
      sentence as candidate boundaries, which inevitably generate a large number of
      negatives for classifiers. The imbalanced instances seriously mislead classifiers
      and result in lower performance. This paper proposes a dependency-based candidate
      boundary selection method (DCBS), which selects the most likely tokens as
      candidate boundaries and removes the exceptional tokens which have less potential
      to improve the performance based on dependency tree. In addition, we employ the
      composite kernel to integrate lexical and syntactic information and demonstrate
      the effectiveness of structured syntactic features for hedge scope detection.
      Experiments on the CoNLL-2010 Shared Task corpus show that our method achieves
      71.92% F1-score on the golden standard cues, which is 4.11% higher than the
      system without using DCBS. Although the candidate boundary selection method is
      only evaluated on hedge scope detection here, it can be popularized to other
      kinds of scope learning tasks. 

PMID- 26218848
TI  - Molecular markers and pathway analysis of colorectal carcinoma in the Middle
      East.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the
      world. A newly proposed integrated pathway comprising traditional, alternate, and
      serrated pathways by genetic and epigenetic factors was defined recently and
      hypothesized to play a role in the pathogenesis of CRC; however, to the authors'
      knowledge, there is a paucity of information regarding these proposed molecular
      pathways in different ethnic groups. METHODS: Molecular characterization of 770
      CRC specimens was performed for microsatellite instability, BRAF, and KRAS by
      polymerase chain reaction and 500 cases for CpG island methylator phenotype
      (CIMP) high phenotype by MethyLight technology. Tumors were assigned to different
      molecular pathways and examined for clinicopathological correlation and survival
      analysis. RESULTS: The traditional pathway constituted 33.4% of CRC cases, the
      alternate pathway comprised 11.6%, and the serrated molecular pathway accounted
      for only 0.8% of Middle Eastern CRC cases. Approximately 54.2% of CRC cases did
      not qualify to fit into any pathway and thus were designated as an unassigned
      group. Molecular pathways were found to be significantly associated with tumor
      site and grade. A subset of cases with an uncategorized pathway demonstrated a
      significant survival difference (P = .0079). CONCLUSIONS: The serrated pathway
      was found to account for a very low percentage of the CRC patient cohort in the
      current study. The unassigned group accounted for the majority of Middle Eastern
      CRC cases, and therefore methods of CRC pathway analysis might not be applicable
      to this ethnic group. The current study demonstrates the need to unravel the
      molecular genetic basis of this disease to further subcategorize these CRC cases.
      It also identifies a need for further studies on different populations for a
      better understanding of their exact role and incidence.

PMID- 26218849
TI  - An observational study of the real-life management of psoriasis patients treated
      with etanercept according to the new reimbursement criteria (in Belgium).
AB  - BACKGROUND: This study described the number of patients with psoriasis receiving
      flexible (continuous/intermittent) dosing with etanercept (ETN) and the real
      world economic impact. METHODS: BeFlex was a prospective, observational study
      with a >=1 year follow-up. Patients >=18 years with moderate-to-severe psoriasis
      who were starting or re-starting treatment with ETN in alignment with Belgian
      reimbursement criteria were included. Cost of ETN was compared with cost of
      adalimumab, ustekinumab and infliximab using estimates from the National
      Institute for Sickness and Disability Insurance (INAMI/RIZIV). RESULTS: In the
      flexible-dosing cohort (n = 121 with dose-regimen data), 66% were treated
      continuously and 34% intermittently. Baseline characteristics were similar across
      dosing cohorts. In the per-protocol cohort (n = 138), average ETN treatment
      duration/year was 40 weeks; 43 weeks continuous and 33 weeks intermittent. The
      overall mean interruption duration was 3.9 weeks/treatment cycle; 0.2 week
      continuous and 11.1 weeks intermittent. Mean dose/year was 2065 mg; 2182 mg
      continuous and 1660 mg intermittent. Flexible ETN dosing reduced the cost by 20%
      versus INAMI/RIZIV estimates. The theoretical cost of the other continuously
      dosed biologics was 28-44% higher than that of flexible ETN. CONCLUSION:
      Approximately one-third of Belgian patients received intermittent ETN treatment.
      Flexible ETN dosing was more cost-effective than treatment with biologic agents
      that require continuous dosing.

PMID- 26218850
TI  - A double amino-acid change in the HLA-A peptide-binding groove is associated with
      response to psychotropic treatment in patients with schizophrenia.
AB  - The choice of an efficient psychotropic treatment for patients with schizophrenia
      is a key issue to improve prognosis and quality of life and to decrease the
      related burden and costs. As for other complex disorders, response to drugs in
      schizophrenia is highly heterogeneous and the underlying molecular mechanisms of
      this diversity are still poorly understood. In a carefully followed-up cohort of
      schizophrenic patients prospectively treated with risperidone or olanzapine, we
      used a specially designed single-nucleotide polymorphism (SNP) array to perform a
      large-scale genomic analysis and identify genetic variants associated with
      response to psychotropic drugs. We found significant associations between
      response to treatment defined by the reduction in psychotic symptomatology 42
      days after the beginning of treatment and SNPs located in the chromosome 6, which
      houses the human leukocyte antigen (HLA). After imputation of the conventional
      HLA class I and class II alleles, as well as the amino-acid variants, we observed
      a striking association between a better response to treatment and a double amino
      acid variant at positions 62 and 66 of the peptide-binding groove of the HLA-A
      molecule. These results support the current notion that schizophrenia may have
      immune-inflammatory underpinnings and may contribute to pave the way for
      personalized treatments in schizophrenia. 

PMID- 26218852
TI  - Effects of cortisol administration on craving in heroin addicts.
AB  - Heroin dependence is a severe and chronically relapsing substance use disorder
      with limited treatment options. Stress is known to increase craving and drug
      taking behavior, but it is not known whether the stress hormone cortisol mediates
      these stress effects or whether cortisol may rather reduce craving, for example,
      by interfering with addiction memory. The aim of the present study was to
      determine the effects of cortisol administration on craving in heroin-dependent
      patients and to determine whether the effects depend on the daily dose of heroin
      consumption. We used a double-blind, placebo-controlled, cross-over study in 29
      heroin-dependent patients in a stable heroin-assisted treatment setting. A single
      oral dose of 20 mg of cortisol or placebo was administered 105 min before the
      daily heroin administration. The primary outcome measure was cortisol-induced
      change in craving. Secondary measures included anxiety, anger and withdrawal
      symptoms. For the visual analog scale for craving, we found a significant
      interaction (P = 0.0027) between study medication and heroin-dose group (that is,
      daily low, medium or high dose of heroin). Cortisol administration reduced
      craving in patients receiving a low dose of heroin (before heroin administration:
      P = 0.0019; after heroin administration: P = 0.0074), but not in patients
      receiving a medium or high dose of heroin. In a picture-rating task with drug
      related pictures, cortisol administration did not affect the ratings for the
      picture-characteristic craving in all the three heroin-dose groups. Cortisol also
      did not significantly affect secondary outcome measures. In conclusion, a single
      administration of cortisol leads to reduced craving in low-dose heroin addicts.
      The present findings might have important clinical implications with regard to
      understanding stress effects and regarding treatment of addiction.

PMID- 26218853
TI  - Comparing the performance of English mental health providers in achieving patient
      outcomes.
AB  - Evidence on provider payment systems that incorporate patient outcomes is limited
      for mental health care. In England, funding for mental health care services is
      changing to a prospective payment system with a future objective of linking some
      part of provider payment to outcomes. This research examines performance of
      mental health providers offering hospital and community services, in order to
      investigate if some are delivering better outcomes. Outcomes are measured using
      the Health of the Nation Outcome Scales (HoNOS) - a clinician-rated routine
      outcome measure (CROM) mandated for national use. We use data from the Mental
      Health Minimum Data Set (MHMDS) - a dataset on specialist mental health care with
      national coverage - for the years 2011/12 and 2012/13 with a final estimation
      sample of 305,960 observations with follow-up HoNOS scores. A hierarchical
      ordered probit model is used and outcomes are risk adjusted with independent
      variables reflecting demographic, need, severity and social indicators. A
      hierarchical linear model is also estimated with the follow-up total HoNOS score
      as the dependent variable and the baseline total HoNOS score included as a risk
      adjuster. Provider performance is captured by a random effect that is quantified
      using Empirical Bayes methods. We find that worse outcomes are associated with
      severity and better outcomes with older age and social support. After adjusting
      outcomes for various risk factors, variations in performance are still evident
      across providers. This suggests that if the intention to link some element of
      provider payment to outcomes becomes a reality, some providers may gain
      financially whilst others may lose. The paper contributes to the limited
      literature on risk adjustment of outcomes and performance assessment of providers
      in mental health in the context of prospective activity-based payment systems. 

PMID- 26218851
TI  - Immune and neurotrophin stimulation by electroconvulsive therapy: is some
      inflammation needed after all?
AB  - A low-grade inflammatory response is commonly seen in the peripheral blood of
      major depressive disorder (MDD) patients, especially those with refractory and
      chronic disease courses. However, electroconvulsive therapy (ECT), the most
      drastic intervention reserved for these patients, is closely associated with an
      enhanced haematogenous as well as neuroinflammatory immune response, as evidenced
      by both human and animal studies. A related line of experimental evidence further
      shows that inflammatory stimulation reinforces neurotrophin expression and may
      even mediate dramatic neurogenic and antidepressant-like effects following
      exposure to chronic stress. The current review therefore attempts a synthesis of
      our knowledge on the neurotrophic and immunological aspects of ECT and other
      electrically based treatments in psychiatry. Perhaps contrary to contemporary
      views, we conclude that targeted potentiation, rather than suppression, of
      inflammatory responses may be of therapeutic relevance to chronically depressed
      patients or a subgroup thereof. 

PMID- 26218854
TI  - Screening and incorporation of rust resistance from Allium cepa into bunching
      onion (Allium fistulosum) via alien chromosome addition.
AB  - Bunching onion (Allium fistulosum L.; 2n = 16), bulb onion (Allium cepa L. Common
      onion group), and shallot (Allium cepa L. Aggregatum group) cultivars were
      inoculated with rust fungus, Puccinia allii, isolated from bunching onion. Bulb
      onions and shallots are highly resistant to rust, suggesting they would serve as
      useful resources for breeding rust resistant bunching onions. To identify the A.
      cepa chromosome(s) related to rust resistance, a complete set of eight A.
      fistulosum - shallot monosomic alien addition lines (MAALs) were inoculated with
      P. allii. At the seedling stage, FF+1A showed a high level of resistance in
      controlled-environment experiments, suggesting that the genes related to rust
      resistance could be located on shallot chromosome 1A. While MAAL, multi
      chromosome addition line, and hypoallotriploid adult plants did not exhibit
      strong resistance to rust. In contrast to the high resistance of shallot, the
      addition line FF+1A+5A showed reproducibly high levels of rust resistance. 

PMID- 26218855
TI  - Contact Antimicrobial Surface Obtained by Chemical Grafting of Microfibrillated
      Cellulose in Aqueous Solution Limiting Antibiotic Release.
AB  - Contact active surfaces are an innovative tool for developing antibacterial
      products. Here, the microfibrillated cellulose (MFC) surface was modified with
      the beta-lactam antibiotic benzyl penicillin in aqueous medium to prepare
      antimicrobial films. Penicillin was grafted on the MFC surface using a suspension
      of these nanofilaments or directly on films. Films prepared from the penicillin
      modified MFC were characterized by Fourier transform infrared spectroscopy,
      contact angle measurements, elemental analysis, and X-ray photoelectron
      spectroscopy and tested for antibacterial activity against the Gram-positive
      Staphylococcus aureus and Gram-negative Escherichia coli. Penicillin-grafted MFC
      films exhibited successful killing effect on Gram-positive bacteria with 3.5-log
      reduction whereas bacteriostatic efficiency was found in penicillin-grafted MFC
      suspension. The zone of inhibition test and leaching dynamic assay demonstrated
      that penicillin was not diffused into the surrounding media, thus proving that
      the films were indeed contact active. Thus, penicillin can be chemically bound to
      the modified substrate surface to produce promising nonleaching antimicrobial
      systems. 

PMID- 26218856
TI  - The boundaries of genocide: Quantifying the uncertainty of the death toll during
      the Pol Pot regime in Cambodia (1975-79).
AB  - The range of estimates of excess deaths under Pol Pot's rule of Cambodia (1975
      79) is too wide to be useful: they range from under 1 to over 3 million, with the
      more plausible estimates still varying from 1 to 2 million. By stochastically
      reconstructing population dynamics in Cambodia from extant historical and
      demographic data, we produced interpretable distributions of the death toll and
      other demographic indicators. The resulting 95 per cent simulation interval (1.2
      2.8 million excess deaths) demonstrates substantial uncertainty over the exact
      scale of mortality, yet it still excludes nearly half of the previous death-toll
      estimates. The 1.5-2.25 million interval contains 69 per cent of the simulations
      for the actual number of excess deaths, more than the wider (1-2 million) range
      of previous plausible estimates. The median value of 1.9 million excess deaths
      represents 21 per cent of the population at risk. Supplementary material for this
      article is available at: http://dx.doi.org/10.1080/00324728.2015.1045546.

PMID- 26218858
TI  - Delayed laparoscopic cholecystectomy increases the total hospital stay compared
      to an early laparoscopic cholecystectomy after acute cholecystitis: an updated
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The objective of this study was to review the available prospective,
      randomized, controlled trials to determine whether an early (ELC) or a delayed
      (DLC) approach to a laparoscopic cholecystectomy is associated with an increase
      in length of hospitalization after acute cholecystitis. METHODS: Medline, the
      Cochrane Trials Register and EMBASE were searched for prospective, randomized,
      controlled trials (RCTs) comparing ELC versus DLC, published up to May 2014. A
      meta-analysis was performed using Review Manager 5.0. RESULTS: Nine RCTs were
      included in a total of 617 who underwent ELC and 603 patients who underwent DLC
      after acute cholecystitis. The mean hospital stay was 5.4 days in the ELC group
      and 9.1 days in the DLC group. The meta-analysis showed a mean hospital stay
      significantly lower in the ELC group [medical doctor (MD) = 3.24, 95% confidence
      interval (CI) = 1.95-4.54, P < 0.001]. The major biliary duct injury rate in the
      ELC group was 0.8% (2/247) and 0.9% (2/223) in the DLC group. The meta-analysis
      showed no significant difference between the ELC and DLC groups [relative risk
      (RR) =0.96, 95%CI = 0.25-3.73, P = 0.950]. CONCLUSION: DLC is associated with a
      longer total hospital stay but equivalent morbidity as compared to ELC for
      patients presenting with acute cholecystitis. ELC would appear to be the
      treatment of choice for patients presenting with ELC.

PMID- 26218859
TI  - Age-related changes to wheelchair efficiency and sprint power output in novice
      able-bodied males.
AB  - This study examined the effect of age on sub-maximal wheelchair propulsion
      efficiency and sprint power output (SPO) in inexperienced able-bodied males. Two
      age groups were used for this study: a younger adult group (N = 10; mean age 24.8
      +/- 3.0 years) and an older adult group (N = 8; mean age 70.9 +/- 5.2 years). No
      one had prior manual wheelchair experience. The primary outcome measures were
      gross mechanical efficiency (GME), mechanical effectiveness (ME) during sub
      maximal treadmill wheeling and SPO during a max sprint test. There were no
      significant differences in GME; however, there was a significant difference in ME
      [0.74 +/- 0.12 and 0.62 +/- 0.08 (p = 0.007)] and sprint test [SPO = 224.66 +/-
      79.25 and 125.98 +/- 53.02 (W) (p = 0.008)], for younger and older adults,
      respectively. Healthy, active older individuals can have a physiological capacity
      similar to younger populations to wheel sub-maximally, but their ME and lower SPO
      reduce the ability to propel manual wheelchairs during maximal wheeling.
      PRACTITIONER SUMMARY: Understanding the potential for older adults to propel
      wheelchairs is important as the population ages with disabilities. This study
      demonstrated significantly lower ME but not GME in older versus younger adult
      populations. Strength training may be needed to keep older adults active in
      manual wheelchairs.

PMID- 26218860
TI  - Vaccination recommendations for adult patients with autoimmune inflammatory
      rheumatic diseases.
AB  - BACKGROUND: The number of individuals with autoimmune inflammatory rheumatic
      diseases (AIIRDs) treated with immunosuppressive drugs is increasing steadily.
      The variety of immunosuppressive drugs and, in particular, biological therapies
      is also rising. The immunosuppressants, as well as the AIIRD itself, increase the
      risk of infection in this population. Thus, preventing infections by means of
      vaccination is of utmost importance. New Swiss vaccination recommendations for
      AIIRD patients were initiated by the Swiss Federal Office of Public Health and
      prepared by a working group of the Federal Commission for Vaccination Issues as
      well as by consultation of international experts. METHODS: A literature search
      was performed in electronic databases (Cochrane, Medline, PubMed, Embase). In
      addition, unpublished literature was identified through a targeted website search
      of relevant organisations and international conferences dealing with vaccination,
      infectious diseases and rheumatology. RESULTS: Although data are scarce, the
      following main points were retrieved from the literature. Inactivated vaccines
      are safe, but their immunogenicity may be reduced in AIIRD patients, especially
      if they are under immunosuppressive therapy. Rituximab and abatacept appear to
      reduce significantly immune responses after vaccination. Live vaccines are
      generally contraindicated under immunosuppressive therapy owing to safety
      concerns. Specific exceptions, as well as time intervals for the administration
      of live vaccines after interruption of an immunosuppressive therapy, have been
      formulated in this article. CONCLUSION: More evidence regarding the
      immunogenicity and safety of vaccinations in AIIRD patients under various
      therapies is needed. Vaccination recommendations should be updated on a regular
      basis, as more scientific data will become available.

PMID- 26218861
TI  - Failed Obstetric Spinal Anesthesia in a Nigerian Teaching Hospital: Incidence and
      Risk Factors.
AB  - BACKGROUND: In a retrospective survey, we found 1% cases with complete and
      partial failure of spinal anesthesia for cesarean delivery between 2008 and 2010,
      which we attributed to underreporting because of the study design. In this
      prospective study, we determined the incidence of failed spinal anesthesia and
      identified the factors that increased its risk. METHODS: This prospective,
      observational study consisted of all spinal anesthetics administered for cesarean
      delivery surgery from January 2011 to December 2013. Our definition of failure
      covered complete (preoperative) failure to achieve a pain-free operative
      condition and pain during surgery (intraoperative failure). RESULTS: Of a total
      of 3568 cesarean deliveries, there were 3239 (90.8%) spinal blocks, and the
      overall failure was 294 (9.1%). These were rescued by conversion to general
      anesthesia (22.8%) and repeating spinal (23.1%) and IV analgesic supplementation
      (54.1%). Analysis by logistic regression model indicated that factors associated
      with failure were the level of experience of the anesthesia provider as shown by
      senior registrar (adjusted risk ratio [RR], 1.4; 95% confidence interval [CI],
      1.0-1.9), >1 lumbar puncture attempt (adjusted RR, 1.5; 95% CI, 1.1-1.9), and use
      of the L4/L5 interspace (adjusted RR, 1.7; 95% CI, 1.4-2.0). CONCLUSIONS: The
      rate of failed spinal anesthesia from this study was high. The independent
      predictors of failure were multiple lumbar puncture attempts, use of the L4/L5
      interspace, and the level of experience of the anesthesia provider. It is
      imperative to develop clear guidelines to standardize our obstetric spinal
      anesthetic practice as well as the management of failures.

PMID- 26218862
TI  - Dexmedetomidine Pharmacology in Neonates and Infants After Open Heart Surgery.
AB  - BACKGROUND: Dexmedetomidine is a highly selective alpha2-agonist with hypnotic,
      analgesic, and anxiolytic properties. Despite off-label administration,
      dexmedetomidine has found a niche in critically ill neonates and infants with
      congenital heart disease because of its minimal effects on respiratory function
      at sedative doses, facilitating early extubation and fast-track postoperative
      care. There are little pharmacokinetic data regarding newborns who have immature
      drug metabolizing capacity and who are at risk for reduced dexmedetomidine
      clearance and drug toxicity. The aim of this study was to determine the
      pharmacokinetics of dexmedetomidine in neonates and infants after open heart
      surgery. This study included 23 evaluable neonates (age, 1 day-1 month) and 36
      evaluable infants (age, 1 month-24 months) after open heart surgery. METHODS:
      Full-term neonates and infants requiring mechanical ventilation after open heart
      surgery received dexmedetomidine in a dose-escalation study. Dexmedetomidine was
      administered as a loading dose over 10 minutes followed by a continuous IV
      infusion up to 24 hours. Cohorts of 12 infants were enrolled sequentially to
      receive 0.35, 0.7, or 1 MUg/kg dexmedetomidine followed by 0.25, 0.5, or 0.75
      MUg/kg/h dexmedetomidine, respectively. Cohorts of 9 neonates received 0.25,
      0.35, or 0.5 MUg/kg dexmedetomidine followed by 0.2, 0.3, or 0.4 MUg/kg/h
      dexmedetomidine, respectively. Plasma dexmedetomidine concentrations were
      determined using a validated high-performance liquid chromatography-tandem mass
      spectrometry assay. A population nonlinear mixed effects modeling approach was
      used to characterize dexmedetomidine pharmacokinetics. RESULTS: Pharmacokinetic
      parameters of dexmedetomidine were estimated using a 2-compartment disposition
      model with weight allometrically scaled as a covariate on drug clearance,
      intercompartmental clearance, central and peripheral volume of distributions and
      age, total bypass time, and intracardiac shunting on clearance. Dexmedetomidine
      demonstrated a plasma drug clearance of 657 * (weight/70) mL/min,
      intercompartmental clearance of 6780 * (weight/70) mL/min, central volume of
      distribution of 88 * (weight/70) L and peripheral volume of distribution of 112 *
      (weight/70) L for a typical subject with age >1 month with a cardiopulmonary
      bypass time of 60 minutes and without right-to-left intracardiac shunt.
      Dexmedetomidine pharmacokinetics may be influenced by age during the neonatal
      period, weight, total bypass time, and presence of intracardiac shunt.
      CONCLUSIONS: Dexmedetomidine clearance is significantly diminished in full-term
      newborns and increases rapidly in the first few weeks of life. The dependence of
      clearance on age during the first few weeks of life reflects the relative
      immaturity of metabolic processes during the newborn period. Continuous infusions
      of up to 0.3 MUg/kg/h in neonates and 0.75 MUg/kg/h in infants were well
      tolerated after open heart surgery.

PMID- 26218863
TI  - Major Upper Abdominal Surgery Alters the Calibration of Bioreactance Cardiac
      Output Readings, the NICOM, When Comparisons Are Made Against Suprasternal and
      Esophageal Doppler Intraoperatively.
AB  - BACKGROUND: Minimally invasive continuous cardiac output measurements are
      recommended for use during anesthesia to guide fluid therapy, but such
      measurements must trend changes reliably. The NICOM Cheetah, a BioReactance
      monitor, is being recommended for intraoperative use. To validate its use,
      Doppler methods, suprasternal USCOM and esophageal CardioQ, were used in tandem
      to provide reliable estimates of changing trends in cardiac output. Preliminary
      comparisons showed that upper abdominal surgical interventions caused shifts in
      the calibration of the NICOM. The purpose of this study was to confirm and
      measure these calibration shifts. METHODS: Major surgery patients, aged 58 (32
      78) years, 12 males and 15 females, were divided into 4 study groups: (a)
      controls-lower abdominal or peripheral surgery (n = 9); (b) laparoscopy with
      abdominal insufflation (n = 6); (c) open upper abdominal surgery with large
      multiblade retractor placement (n = 6) and (d) head-down robotic surgery (n = 6).
      Simultaneous NICOM and Doppler readings were taken every 15 to 30 minutes. Within
      individual time plots were drawn, and regression analysis between NICOM-USCOM and
      CardioQ-USCOM readings was performed. Bland-Altman and trend (concordance)
      analyses were also performed. RESULTS: Three hundred ninety NICOM comparisons
      were collected. Duration of surgeries was 4 (11/2 to 11) hours, with 7 to 22 sets
      of readings per case. Mean (SD) cardiac index from USCOM readings was 3.5(1.0)
      L/min/m. Individual time plots showed shifts in NICOM calibration relative to
      Doppler (USCOM) in cardiac index of +/-0.9 (0.6-1.4) L/min/m during the surgical
      interventions. In 13 of 18 patients (72%), the shift was downward, but upward
      shifts did occur. Within-individual correlations between CardioQ-USCOM showed
      good trending R = 0.87 (range, 0.60-0.97). In the control group, NICOM-USCOM also
      showed good trending R = 0.89 (0.69-0.97). However, trending was poor in the
      intervention groups, R = 0.43 (0.03-0.71; P < 0.0001). The Bland-Altman
      percentage error between NICOM-USCOM (57 [54-60]%) was greater than that between
      CardioQ-USCOM (42 [40-44]%) (P < 0.0001). Concordance rates were 82 (77-88)% from
      101 data pairs and 95 (90-99)% from 72 data pairs, respectively. CONCLUSIONS:
      Doppler monitoring used in tandem provided valid trend lines of cardiac output
      changes against which NICOM readings could be compared. Intraoperatively, the
      NICOM was shown to track changes in cardiac output reliably in most
      circumstances. However, surgical interventions to the upper abdomen caused shifts
      in readings by >1 L/min/m, and the direction of the shifts was unpredictable.
      Anesthesiologists need to be aware of these calibration shifts and anticipate
      their occurrence, whenever the NICOM is used intraoperatively.

PMID- 26218864
TI  - Extravascular Lung Water and Pulmonary Vascular Permeability Index Measured at
      the End of Surgery Are Independent Predictors of Prolonged Mechanical Ventilation
      in Patients Undergoing Liver Transplantation.
AB  - BACKGROUND: Pulmonary edema (PE) after orthotopic liver transplantation (OLT) may
      compromise the postoperative course and prolong the duration of mechanical
      ventilation (MV) and intensive care unit length of stay. Hemodynamic monitoring
      with transpulmonary thermodilution permits quantification of extravascular lung
      water index (ELWI) and calculation of the pulmonary vascular permeability index
      (PVPI), which is the ratio between the ELWI and the pulmonary blood volume. This
      ratio can discriminate between PE hydrostatic and nonhydrostatic PE. We
      investigated the relationship between ELWI and PVPI values, measured at the end
      of surgery, and prolonged MV (PMV) in patients after OLT. METHODS: We
      retrospectively studied 93 consecutive patients who underwent OLT. We recorded
      preoperative data including spirometry, echocardiography, severity liver disease
      with the Model for End-Stage Liver Disease score, and the Child-Pugh
      classification scores. Intraoperatively, we performed hemodynamic measurements
      with transpulmonary thermodilution and pulmonary arterial catheters after the
      induction of anesthesia, 10 minutes before reperfusion, and at the end of
      surgery. Moreover, we recorded the length of surgery, the amount of IV volume
      infused, the results of blood coagulation analyses, and blood transfusion.
      Postoperatively, we recorded the duration of MV and intensive care unit length of
      stay, mortality, and graft function. Patients were then classified as requiring
      PMV (>48 hours after surgery) or not. Statistical analyses, preoperative and
      intraoperative variables between patients with and without PMV, were compared
      using Mann-Whitney U tests. Receiver-operating characteristic curves were used to
      evaluate the ability of preoperative and intraoperative variables to predict PMV.
      RESULTS: Twelve patients required PMV after surgery. Patients who required PMV
      exhibited increased ELWI (11.6 +/- 3 mL/kg vs 9.3 +/- 2 mL/kg, P = 0.0099) and
      PVPI values (2.94 +/- 1 vs 1.8 +/- 0.6, P = 0.000015) at the end of surgery. The
      areas under the receiver-operating characteristic curve were 0.890 +/- 0.04 for
      PVPI with a 99% confidence interval of 0.782 to 0.958 and 0.730 +/- 0.08 for ELWI
      with a 99% confidence interval of 0.594 to 0.839. Using a cutoff of 2.3 for PVPI
      allowed a sensitivity = 91.7%, a specificity = 83.8, a positive predictive value
      = 45.8%, and a negative predictive value = 98.5% for predicting PMV. A cutoff of
      12 for ELWI allowed a sensitivity of 50%, specificity of 85%, positive predictive
      value of 33.3%, and negative predictive value of 91.9% for PMV. CONCLUSIONS: PVPI
      and ELWI values obtained at the end of OLT are useful for predicting the need for
      postoperative PMV.

PMID- 26218865
TI  - Stress Increases the Negative Effects of Chronic Pain on Hippocampal
      Neurogenesis.
AB  - BACKGROUND: Patients with chronic pain often suffer from affective disorders and
      cognitive decline, which significantly impairs their quality of life. In
      addition, many of these patients also experience stress unrelated to their
      illness, which can aggravate their symptoms. These nociceptive inputs are
      received by the hippocampus, in which maladaptive neuroplastic changes may occur
      in the conditions of chronic pain. The hippocampus is a structure involved in
      emotionality, learning, and memory, and the proliferating cells in the granular
      layer of the hippocampal dentate gyrus respond to chronic pain by slowing their
      turnover. However, whether the maturation, survival, and integration of newborn
      cells in the hippocampus are affected by chronic pain remains unclear. In
      addition, it is unknown whether an added stress may increase this effect.
      METHODS: We have evaluated the proliferation, differentiation, and survival of
      newborn hippocampal cells in a rat model of neuropathic pain (chronic
      constriction injury), with or without stress (chronic immobilization), by
      assessing the incorporation of bromodeoxyuridine into proliferating cells and
      immunostaining. RESULTS: The data obtained indicated that there was a decrease in
      the number of proliferating cells 8 days after nerve injury in animals subjected
      to neuropathic pain, an effect that was exacerbated by stress. Moreover, 4 weeks
      after nerve injury, neuropathic pain was associated with a loss of neuroblasts
      and the reduced survival of new mature neurons in the hippocampal granular layer,
      phenomena that also were increased by stress. By contrast, the rate of
      differentiation was not affected in this paradigm. CONCLUSIONS: Neuropathic pain
      negatively influences hippocampal neurogenesis (proliferation and survival), and
      this effect is exacerbated by stress. These neuroplastic changes may account for
      the affective and cognitive impairment seen in patients with chronic pain.

PMID- 26218867
TI  - Big data, big knowledge: big data for personalized healthcare.
AB  - The idea that the purely phenomenological knowledge that we can extract by
      analyzing large amounts of data can be useful in healthcare seems to contradict
      the desire of VPH researchers to build detailed mechanistic models for individual
      patients. But in practice no model is ever entirely phenomenological or entirely
      mechanistic. We propose in this position paper that big data analytics can be
      successfully combined with VPH technologies to produce robust and effective in
      silico medicine solutions. In order to do this, big data technologies must be
      further developed to cope with some specific requirements that emerge from this
      application. Such requirements are: working with sensitive data; analytics of
      complex and heterogeneous data spaces, including nontextual information;
      distributed data management under security and performance constraints;
      specialized analytics to integrate bioinformatics and systems biology information
      with clinical observations at tissue, organ and organisms scales; and specialized
      analytics to define the "physiological envelope" during the daily life of each
      patient. These domain-specific requirements suggest a need for targeted funding,
      in which big data technologies for in silico medicine becomes the research
      priority. 

PMID- 26218866
TI  - Contralateral Hyperalgesia from Injection of Endothelin-1 into the Ipsilateral
      Paw Requires Efferent Conduction into the Contralateral Paw.
AB  - BACKGROUND: Contralateral hyperalgesia, occurring after unilateral injury, is
      usually explained by central sensitization in spinal cord and brain. We
      previously reported that injection of endothelin-1 (ET-1) into one rat hindpaw
      induces prolonged mechanical and chemical sensitization of the contralateral
      hindpaw. Here, we examined the role of contralateral efferent activity in this
      process. METHODS: ET-1 (2 nmol, 10 MUL) was injected subcutaneously into the
      plantar surface of right (ipsilateral) hindpaw (ILP), and the thermal response
      latency and mechanical threshold for nocifensive withdrawal were determined by
      the use of, respectively, plantar radiant heating and von Frey filaments, for
      both ILP and contralateral hindpaws (CLP). Either paw was anesthetized for 60
      minutes by direct injection of bupivacaine (0.25%, 40 MUL), 30 minutes before ET
      1. Alternatively, the contralateral sciatic nerve was blocked for 6 to 12 hours
      by percutaneous injection of bupivacaine-releasing microspheres 30 minutes before
      injection of ET-1. Systemic actions of these bupivacaine formulations were
      simulated by subcutaneous injection at the nuchal midline. RESULTS: After the
      injection of ET-1, the mechanical threshold of both ILP and CLP decreased by 2
      hours, appeared to be lowest around 24 hours, and recovered through 48 hours to
      preinjection baseline at 72 hours. These hypersensitive responses were suppressed
      by bupivacaine injected into the ipsilateral paw before ET-1. Injection of the
      CLP by bupivacaine also suppressed the hypersensitivity of the CLP at all test
      times, and that of the ILP, except at 2 hours when it increased the sensitivity.
      This same pattern of change occurred when the contralateral sciatic nerve was
      blocked by bupivacaine-releasing microspheres. The systemic actions of these
      bupivacaine formulations were much smaller and only reached significance at 24
      hours post-ET-1. Thermal hypersensitivity after ET-1 injection also occurred in
      both ILP and CLP and showed the same pattern in response to the 2 contralateral
      anesthetic procedures. CONCLUSIONS: These results show that efferent transmission
      through the contralateral innervation into the paw is necessary for contralateral
      sensitization by ET-1, suggesting that the release of substances by distal nerve
      endings is involved. The release of substances in the periphery is essential for
      contralateral sensitization by ET-1 and may also contribute to secondary
      hyperalgesia, occurring at loci distant from the primary injury, that occurs
      after surgery or nerve damage.

PMID- 26218868
TI  - Prostate carcinoma with positive margins at radical prostatectomy: role of tumour
      zonal origin in biochemical recurrence.
AB  - OBJECTIVE: To assess the influence of tumour zonality on biochemical recurrence
      (BCR) after radical prostatectomy (RP) with a histologically confirmed positive
      surgical margin (PSM). PATIENTS AND METHODS: Data from 382 patients that
      underwent RP with either transition zone (TZ) or peripheral zone (PZ) tumours
      involving PSMs between 1998 and 2010 were retrieved from the Abbott West
      Australian Prostatectomy Database. Statistical analysis was used to evaluate the
      relationship of various tumour clinicopathological parameters, e.g. zonal origin
      of tumour, tumour volume, Gleason score, and stage to the development of BCR
      RESULTS: There were 51 TZ and 331 PZ tumours with PSMs identified. The TZ tumours
      compared with PZ tumours were larger (median 5.67 vs 3.64 mL, P < 0.001), more
      frequently lower grade (Gleason score 6 33% vs 5%, P < 0.01), organ confined (51%
      vs 35.6%, P = 0.073), and preferentially involved the bladder neck (49% vs 6%, P
      < 0.001). Tumour zonality was not associated with BCR for the entire cohort. TZ
      and PZ tumours had similar 5-year BCR-free survival rates (58% vs 63%, P = 0.691)
      and comparable time to development of BCR (14.4 vs 19.2 months, P = 0.346). On
      univariate analysis, preoperative PSA level, PSM at the bladder neck, tumour
      volume, Gleason score (P < 0.001) and tumour stage were independent predictors of
      BCR for the entire cohort. On multivariate analysis tumour volume and Gleason
      score retained significance as independent predictors of BCR. Tumour zonality was
      not directly associated with BCR. Of the patients who received adjuvant therapy,
      the incidence of BCR was similar for TZ and PZ tumours (58% vs 67%, P = 0.077),
      although TZ tumours failed significantly earlier (mean 4.4 vs 16.4 months, P =
      0.037). CONCLUSIONS: PSA recurrence in patients with histologically confirmed
      PSMs after RP is independent of the zonal location of the index tumour. However,
      tumour zonal origin may have an indirect influence on PSA relapse, as TZ tumours
      tend to be of large volume and more likely involve the bladder neck margin, both
      risk factors for BCR. Bladder neck margin involvement is associated with higher
      rates of BCR than other sites of PSMs. The preoperative identification of TZ
      tumours might aid surgical planning with appropriate alteration of RP technique
      to incorporate wider surgical margins at the bladder neck. Adjuvant radiotherapy
      appears to be associated with adverse outcome for TZ tumours, a novel finding
      which warrants further investigation.

PMID- 26218869
TI  - Control of Photoluminescence of Carbon Nanodots via Surface Functionalization
      using Para-substituted Anilines.
AB  - Carbon nanodots (C-dots) are a kind of fluorescent carbon nanomaterials, composed
      of polyaromatic carbon domains surrounded by amorphous carbon frames, and have
      attracted a great deal of attention because of their interesting properties.
      There are still, however, challenges ahead such as blue-biased photoluminescence,
      spectral broadness, undefined energy gaps and etc. In this report, we chemically
      modify the surface of C-dots with a series of para-substituted anilines to
      control their photoluminescence. Our surface functionalization endows our C-dots
      with new energy levels, exhibiting long-wavelength (up to 650 nm)
      photoluminescence of very narrow spectral widths. The roles of para-substituted
      anilines and their substituents in developing such energy levels are thoroughly
      studied by using transient absorption spectroscopy. We finally demonstrate light
      emitting devices exploiting our C-dots as a phosphor, converting UV light to a
      variety of colors with internal quantum yields of ca. 20%. 

PMID- 26218870
TI  - Influence of Si addition on the microstructure and mechanical properties of Ti
      35Nb alloy for applications in orthopedic implants.
AB  - In the development of new materials for orthopedic implants, special attention
      has been given to Ti alloys that show biocompatible alloy elements and that are
      capable of reducing the elastic modulus. Accordingly, Ti-Nb-Si alloys show great
      potential for application. Thus, this is a study on the microstructures and
      properties of Ti-35Nb-xSi alloys (x=0, 0.15, 0.35 and 0.55) (wt%) which were
      thermally treated and cooled under the following conditions: furnace cooling
      (FC), air cooling (AC), and water quenching (WQ). The results showed that Si
      addition is effective to reduce the density of omega precipitates making beta
      more stable, and to produce grain refinement. Silicides, referred as (Ti,Nb)3Si,
      were formed for alloys containing 0.55% Si, and its formation presumably occurred
      during the heating at 1000 degrees C. In all cooling conditions, the hardness
      values increased with the increasing of Si content, as a result from the strong
      Si solid solution strengthening effect, while the elastic modulus underwent a
      continuous reduction due to the reduction of omega precipitates in beta matrix.
      Lower elastic moduli were observed in water-quenched alloys, which concentration
      of 0.15% Si was more effective in their reduction, with value around 65 GPa.
      Regarding Ti-35Nb-xSi alloys (x=0, 0.15 and 0.35), the "double yield point"
      phenomenon, which is typical of alloys with shape memory effect, was observed.
      The increase in Si concentration also produced an increase from 382 MPa to 540
      MPa in the alloys' mechanical strength. Ti-35Nb-0.55Si alloy, however, showed
      brittle mechanical behavior which was related to the presence of silicides at the
      grain boundary.

PMID- 26218871
TI  - Effects of Atomoxetine and Osmotic Release Oral System-Methylphenidate on
      Executive Functions in Patients with Combined Type Attention
      Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: The aim of this study was to evaluate and compare the effects of
      atomoxetine (ATX) and osmotic release oral system-methylphenidate (OROS-MPH)
      therapies on executive functions, activities, treatment response time, and
      adverse effects based on discernible clinical effects in children with combined
      type attention-deficit/hyperactivity disorder (ADHD). METHODS: The study sample
      consisted of 43 children 7-12 years of age, who presented to the outpatient
      clinic with inattention, hyperactivity, and impulsivity for the first time, and
      were diagnosed as having combined type ADHD according to Diagnostic and
      Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria but had not
      previously used any medication for ADHD. The Wisconsin Card Sorting Test (WCST),
      Stroop Test TBAG Form (STP), and Visual Auditory Digit Span B (VADS B) were
      applied to all the patients included. Neuropsychological tests were repeated in
      33 patients with good clinical recovery based on the Clinical Global Impressions
      Improvement (CGI-I) scale (CGI-I <=2) at the week in which clinical recovery was
      observed. The time limit for treatment response was set as 20 weeks. RESULTS: It
      was found that there was significantly increased performance in executive
      functions with ATX and OROS-MPH in both groups. It was seen that although
      significantly increased performance was achieved in both perseveration and
      conceptual learning and reasoning domains by both agents, there was increased
      performance in more domains by the OROS-MPH group in WSCT. Mean doses were 1.31+/
      0.37 mg/kg/day in the ATX group and 0.90+/-0.29 mg/kg/day in the OROS-MPH group.
      Comparable effectiveness (76.19% for ATX vs. 77.27% for OROS-MPH) and adverse
      effects (57.14% for ATX vs. 54.54% for OROS-MPH) were detected in both groups,
      whereas there was a significant difference in clinical response times between the
      groups (13 weeks for ATX vs. 7 weeks for OROS-MPH, p <0.001). CONCLUSIONS: At the
      end of the study, it was seen that clinical recovery achieved by ATX and OROS-MPH
      therapy was associated with improved cognitive processes, and that these agents
      do not only lead to behavioral changes but also to an improvement in cognitive
      processes. In addition, improvements in cognitive processes occurred
      simultaneously with behavioral recovery. Behavior is the result of neurocognitive
      processes, and further studies on the domains that these drugs affect, or the way
      in which these agents exert their effects, are needed.

PMID- 26218872
TI  - Spatial Variation of Phosphorous Retention Capacity in Subsurface Flow
      Constructed Wetlands: Effect of Wetland Type and Inflow Loading.
AB  - For verification of spatial distribution of phosphorous retention capacity in
      constructed wetlands systems(CWs), two horizontal subsurface flow(HSSF) CWs and
      two vertical subsurface flow(VSSF) CWs, using sand as substrate and Typha
      latifolia as wetland plants, were constructed and put into use for synthetic
      wastewater treatment. Five months later, significant spatial variations of TP and
      inorganic phosphorus(Ca-P, Fe-P and Al-P) were observed, which were found to be
      greatly affected by CWs type and hydraulic loading. The results revealed that
      though spatial distribution of Fe-P and Al-P displayed a similar order of
      substrate content as "rhizosphere" > "near-rhizosphere" > "non-rhizosphere" and
      "inflow section" > "outflow section" regardless of types and loading, the
      distribution of Ca-P was positively correlated to that of Fe-P and Al-P in HSSF
      CWs, while negative correlation was shown in VSSF CWs. As a result, TP spatial
      distribution in HSSF CWs demonstrated a greater dissimilarity than that in VSSF
      CWs. For HSSF CWs with low hydraulic loading, the lowest TP content was found in
      non-rhizosphere substrate of outflow section, while the highest one was
      discovered in rhizonsphere substrate of inflow section. The values in 6 parts of
      areas ranged from 0.138 g.kg-1 to 2.710 g.kg-1, which also were from -33.5% to
      1209% compared to the control value. On contrast, spatial difference of TP
      content in substrates of VSSF CWs was insignificant, with a variation ranging
      from 0.776 g.kg-1 to 1.080 g.kg-1, that was 275% to 421% higher than the control
      value. In addition, when hydraulic loading was increased, TP content in VSSF CWs
      sharply decreased, ranging from 0.210 g.kg-1 to 0.634 g.kg-1. Meanwhile,
      dissimilarity of TP spatial distribution in HSSF CWs was reduced, with TP content
      ranging from 0.258 g.kg-1 to 2.237 g.kg-1. The results suggested that P spatial
      distribution should be taken into account for CWs design and operation. 

PMID- 26218873
TI  - Differential Immunometabolic Phenotype in Th1 and Th2 Dominant Mouse Strains in
      Response to High-Fat Feeding.
AB  - Immune reactivity plays an important role in obesity-associated metabolic
      disorders. We investigated immunometabolic phenotype of C57Bl/6 and BALB/c mice,
      prototypical Th1 and Th2-type strains, fed chow or high-fat diet (HFD) for 24
      weeks. In comparison to C57Bl/6 mice, chow-fed BALB/c mice had higher body weight
      and weight gain, lower glycemia, more pronounced liver steatosis, but less
      inflammation and collagen deposition in liver. In response to HFD C57Bl/6 mice
      exhibited higher weight gain, higher glycemia, HbA1c and liver glycogen content,
      increased amount of visceral adipose tissue (VAT) and number of VAT associated
      CD3+CXCR3+ T cells, CD11c+ dendritic cells (DCs) and F4/80+ macrophages than
      BALB/c mice. More numerous CD3+ and CD8+ T lymphocytes, myeloid DCs,
      proinflammatory macrophages (F4/80+CD11b+CD11+ and F4/80+IL-1beta+) and
      CD11b+Ly6Chigh monocytes and higher levels of proinflammatory IL-6, TNF-alpha and
      IFN-gamma were present in liver in HFD-fed C57Bl/6 mice compared with diet
      matched BALB/c mice. As opposed to C57Bl/6 mice, HFD induced marked liver
      steatosis and upregulated the hepatic LXRalpha and PPARgamma genes in BALB/c
      mice. C57Bl/6 mice fed HFD developed liver fibrosis and increased hepatic
      procollagen and TGF-beta mRNA expression, and IL-33, IL-13 and TGF-beta levels in
      liver homogenates, while BALB/c mice fed HFD had scarce collagen deposition in
      liver. The obtained results suggest inherent immunometabolic differences in
      C57Bl/6 and BALB/c mice. Moreover, HFD Th1-type mice on high fat diet regimen are
      more susceptible to adiposity, liver inflammation and fibrosis, while Th2-type
      mice to liver steatosis, which is associated with differential immune cell
      composition in metabolic tissues. Strain-dependent differences in immunometabolic
      phenotype may be relevant for studies of obesity-associated metabolic diseases in
      humans. 

PMID- 26218874
TI  - Graves' Disease Patients with Persistent Hyperthyroidism and Diffuse
      Lymphoplasmacytic Infiltration in the Thyroid Show No Histopathological
      Compatibility with IgG4-Related Disease.
AB  - BACKGROUND: IgG4-related disease is a novel disease entity characterized by
      diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and
      fibrosis into multiple organs. There is still controversy over whether some
      thyroid diseases are actually IgG4-related disease. The objective of this study
      was to elucidate the clinicopathological features of Graves' disease with diffuse
      lymphoplasmacytic infiltration in the thyroid. PATIENTS AND METHODS: Among 1,484
      Graves' disease patients who underwent thyroidectomy, we examined their
      histopathological findings including the degree of lymphoplasmacytic and fibrotic
      infiltration and levels of IgG4-positive plasma cells in the thyroid. Their
      clinical pictures were defined by laboratory and ultrasonographic evaluation.
      RESULTS: A total of 11 patients (0.74%) showed diffuse lymphoplasmacytic
      infiltration in the stroma of the thyroid gland. Meanwhile, other patients showed
      variable lymphoid infiltration ranging from absent to focally dense but no
      aggregation of plasma cells in the thyroid gland. Based on the diagnostic
      criteria of IgG4-related disease, 5 of the 11 subjects had specifically increased
      levels of IgG4-positive plasma cells in the thyroid. Fibrotic infiltration was
      present in only 1 patient developing hypothyroidism after anti-thyroid drug
      treatment for 4 years, but not in the other 10 patients with persistent
      hyperthyroidism. Obliterative phlebitis was not identified in any of the 11
      subjects. Thyroid ultrasound examination showed 1 patient developing
      hypothyroidism who had diffuse hypoechogenicity, but the other hyperthyroid
      patients had a coarse echo texture. CONCLUSIONS: In our study, Graves' disease
      patients with persistent hyperthyroidism who had diffuse lymphoplasmacytic
      infiltration rich in IgG4-positive plasma cells in the thyroid showed no
      concomitant fibrosis or obliterative phlebitis.

PMID- 26218875
TI  - Distinct Patterns of Wnt3a and Wnt5a Signaling Pathway in the Lung from Rats with
      Endotoxic Shock.
AB  - Septic shock is a syndrome with severe hypotension and multiple organ dysfunction
      caused by an imbalance between pro-inflammatory and anti-inflammatory response.
      The most common risk factor of acute lung injury is severe sepsis. Patients with
      sepsis-related acute respiratory distress syndrome have higher mortality. Recent
      studies reveal regulatory roles of Wnt3a and Wnt5a signaling in inflammatory
      processes. Wnt3a signaling has been implicated in anti-inflammatory effects,
      whereas Wnt5a signaling has been postulated to have pro-inflammatory properties.
      However, the balance between Wnt3a and Wnt5a signaling pathway in the lung of
      rats with endotoxic shock has not been determined. Thus, we investigated the
      major components of Wnt3a and Wnt5a signaling pathway in the lung of endotoxemic
      rats. Male Wistar rats were intravenously infused with saline or
      lipopolysaccharide (LPS, 10 mg/kg). The changes of hemodynamics, biochemical
      variables, and arterial blood gas were examined during the experimental period.
      At 6 h after saline or LPS, animals were sacrificed, and lungs were obtained for
      analyzing superoxide production, water accumulation, histologic assessment, and
      protein expressions of Wnt3a and Wnt5a signaling pathway. Animals that received
      LPS showed circulatory failure, multiple organ dysfunction, metabolic acidosis,
      hyperventilation, lung edema, and high mortality. The lung from rats with
      endotoxic shock exhibited significant decreases in the levels of Wnt3a, Fzd1,
      Dsh1, phosphorylated GSK-3beta at Ser9, and beta-catenin. In contrast, the
      expressions of Wnt5a, Fzd5, and CaMKII were up-regulated in the lung of
      endotoxemic rats. These findings indicate the major components of Wnt3a and Wnt5a
      signaling in the lung are disturbed under endotoxic insult. 

PMID- 26218883
TI  - Immediate Effects of Combining Local Techniques in the Craniomandibular Area and
      Hamstring Muscle Stretching in Subjects with Temporomandibular Disorders: A
      Randomized Controlled Study.
AB  - OBJECTIVE: To assess the immediate effects on vertical mouth opening, orofacial
      mechanosensitivity, and lumbar and suboccipital mobility after adding a
      myofascial induction technique to a multimodal protocol in subjects with
      temporomandibular disorders (TMD). DESIGN: A randomized and double-blind
      controlled trial was carried out. SETTINGS/LOCATION: University-based physical
      therapy research clinic. SUBJECTS: Sixty subjects (35+/-11.22 years) with TMD,
      and restricted mobility of the mandibular condyles and the first cervical
      vertebrae, were recruited and randomized to either a control group (CG) (n=30) or
      an experimental group (EG) (n=30). INTERVENTIONS: The CG underwent a
      neuromuscular technique over the masseter muscles and passive hamstring muscle
      stretching. A suboccipital muscle inhibition technique was added to this protocol
      in the EG. OUTCOME MEASURES: Primary measurements were made of vertical mouth
      opening and pressure pain threshold of the masseter muscles. Secondary outcome
      measures included pressure algometry of the trigeminal nerve, suboccipital range
      of motion, and lumbar spine mobility, assessed with the sit-and-reach (SAR) test
      and lumbar forward bending. All evaluations were collected at baseline and
      immediately after intervention. RESULTS: In the intragroup comparison, the EG
      observed an increase in suboccipital flexion (p<0.001; F1,29=14.47; R(2)=0.33)
      and the SAR test (p=0.009; F1,29=7.89; R(2)=0.21). No significant differences
      were found in the between-group comparison for any variable (p>0.05). CONCLUSION:
      The inclusion of a myofascial induction maneuver in a protocol combining local
      (neuromuscular treatment) and distal techniques (hamstring stretching) in
      subjects with TMD has no impact on improving mouth opening, suboccipital and
      lumbar mobility, and orofacial sensitivity to mechanical pressure.

PMID- 26218882
TI  - PKCzeta Promotes Breast Cancer Invasion by Regulating Expression of E-cadherin
      and Zonula Occludens-1 (ZO-1) via NFkappaB-p65.
AB  - Atypical Protein Kinase C zeta (PKCzeta) forms Partitioning-defective (PAR)
      polarity complex for apico-basal distribution of membrane proteins essential to
      maintain normal cellular junctional complexes and tissue homeostasis.
      Consistently, tumor suppressive role of PKCzeta has been established for multiple
      human cancers. However, recent studies also indicate pro-oncogenic function of
      PKCzeta without firm understanding of detailed molecular mechanism. Here we
      report a possible mechanism of oncogenic PKCzeta signaling in the context of
      breast cancer. We observed that depletion of PKCzeta promotes epithelial
      morphology in mesenchymal-like MDA-MB-231 cells. The induction of epithelial
      morphology is associated with significant upregulation of adherens junction (AJ)
      protein E-cadherin and tight junction (TJ) protein Zonula Occludens-1 (ZO-1).
      Functionally, depletion of PKCzeta significantly inhibits invasion and metastatic
      progression. Consistently, we observed higher expression and activation of
      PKCzeta signaling in invasive and metastatic breast cancers compared to non
      invasive diseases. Mechanistically, an oncogenic PKCzeta- NFkappaB-p65 signaling
      node might be involved to suppress E-cadherin and ZO-1 expression and ectopic
      expression of a constitutively active form of NFkappaB-p65 (S536E-NFkappaB-p65)
      significantly rescues invasive potential of PKCzeta-depleted breast cancer cells.
      Thus, our study discovered a PKCzeta - NFkappaB-p65 signaling pathway might be
      involved to alter cellular junctional dynamics for breast cancer invasive
      progression. 

PMID- 26218884
TI  - The Analysis of Normalized Effects on Meridian Current Level After the
      Photoluminescent Bioceramic Treatment on Acupuncture Points.
AB  - OBJECTIVE: This study investigated the advantage of photoluminescent bioceramic
      (PLB) irradiation on meridian channels of abnormal meridian currents, as well as
      the normalization of meridian current levels that may represent the participants'
      physiologic conditions. DESIGN: Statistical analysis of survey data.
      PARTICIPANTS: Forty-six patients with abnormal meridian current in the
      gallbladder (GB). INTERVENTIONS: The effects on the meridian currents were
      measured by an electrodermal instrument after PLB irradiation was applied to the
      GB and other specific acupuncture points. Each meridian was categorized into six
      physiologic levels to evaluate effectiveness after the PLB irradiation: 1,
      extremely low; 2, moderately low; 3, normally low; 4, normally high; 5,
      moderately high; and 6, extremely high level. The positive effect of PLB
      treatment for each meridian could be defined as the normalized ability of the
      meridian level from the extreme values (1, 2, 5, or 6) approaching the normal
      levels (3 or 4). RESULTS: Participants with higher average meridian current (Amc
      >36 MUA) calculated from the currents of 24 Ryodoraku points could be
      significantly normalized after the PLB treatment (p=0.0241). A significant
      positive effect was seen in comparison with the negative effect of PLB on the GB
      meridian (McNemar test, p=0.00004) (n=46*2 for left and right GB meridians). A
      patient with benign facial tremor was treated by PLB for 1 month; PLB improved
      the facial tremor and normalized effects on Amc and meridian current levels at
      the GB, lung, small intestine, bladder, and kidney. CONCLUSION: A method was
      proposed to evaluate the normalization effect of a noninvasive PLB technique on
      the 12 meridians. PLB acupuncture on the specific meridian points could show the
      normalization ability of Amc and GB meridian for the participants.

PMID- 26218886
TI  - Voltammetric detection and profiling of isoprenoid quinones hydrophobically
      transferred from bacterial cells.
AB  - We have developed a novel bacterial detection technique by desiccating a
      bacterial suspension deposited on an electrode. It was also found that the use of
      an indium-tin-oxide (ITO) electrode dramatically improved the resolution of the
      voltammogram, allowing us to observe two pairs of redox peaks, each assigned to
      the adsorption of isoprenoid ubiquinone (UQn) and menaquinone (MKn), which were
      present in the bacterial cell envelopes, giving midpeak potentials of -0.015 and 
      0.25 V versus Ag|AgCl|saturated KCl| at pH 7.0, respectively. Most of the
      microorganisms classified in both the Gram-negative and -positive bacteria gave
      well-defined redox peaks, demonstrating that this procedure made the detection of
      the quinones possible without solvent extraction. It has been demonstrated that
      the present technique can be used not only for the detection of bacteria, but
      also for profiling of the isoprenoid quinones, which play important roles in
      electron and proton transfer in microorganisms. In this respect, the present
      technique provides a much more straightforward way than the solvent extraction in
      that one sample can be prepared in 1 min by heat evaporation of a suspension
      containing the targeted bacteria, which has been applied on the ITO electrode. 

PMID- 26218887
TI  - Antenna Enhanced Graphene THz Emitter and Detector.
AB  - Recent intense electrical and optical studies of graphene have pushed the
      material to the forefront of optoelectronic research. Of particular interest is
      the few terahertz (THz) frequency regime where efficient light sources and highly
      sensitive detectors are very challenging to make. Here we present THz sources and
      detectors made with graphene field effect transistors (GFETs) enhanced by a
      double-patch antenna and an on-chip silicon lens. We report the first
      experimental observation of 1-3 THz radiation from graphene, as well as more than
      3 orders of magnitude performance improvements in a half-edge-contacted GFET
      thermoelectric detector operating at ~2 THz. The quantitative analysis of the
      emitting power and its unusual charge density dependence indicate significant
      nonthermal noise contribution from the GFET. The polarization resolved detection
      measurements with different illumination geometries allow for detailed and
      quantitative analysis of various factors that contribute to the overall detector
      performance. Our experimental results represent a significant advance toward
      practically useful graphene THz devices. 

PMID- 26218885
TI  - Are Mindfulness and Self-Compassion Associated with Sleep and Resilience in
      Health Professionals?
AB  - OBJECTIVES: To describe the relationship between trainable qualities (mindfulness
      and self-compassion), with factors conceptually related to burnout and quality of
      care (sleep and resilience) in young health professionals and trainees. DESIGN:
      Cross-sectional survey. SETTING: Large Midwestern academic health center.
      PARTICIPANTS: 213 clinicians and trainees. OUTCOME MEASURES: Sleep and resilience
      were assessed by using the 8-item PROMIS Sleep scale and the 6-item Brief
      Resilience Scale. Mindfulness and self-compassion were assessed using the 10-item
      Cognitive and Affective Mindfulness Scale, Revised and the 12-item Self
      Compassion Scale. Health was assessed with Patient-Reported Outcomes Measurement
      Information System (PROMIS) Global Health measures, and stress was assessed with
      the 10-item Perceived Stress Scale. After examination of descriptive statistics
      and Pearson correlations, multiple regression analyses were done to determine
      whether mindfulness and self-compassion were associated with better sleep and
      resilience. RESULTS: Respondents had an average age of 28 years; 73% were female.
      Professions included dieticians (11%), nurses (14%), physicians (38%), social
      workers (24%), and other (12%). Univariate analyses showed normative values for
      all variables. Sleep disturbances were significantly and most strongly correlated
      with perceived stress and poorer health, but also with less mindfulness and self
      compassion. Resilience was strongly and significantly correlated with less stress
      and better mental health, more mindfulness, and more self-compassion.
      CONCLUSIONS: In these young health professionals and trainees, sleep and
      resilience are correlated with both mindfulness and self-compassion. Prospective
      studies are needed to determine whether training to increase mindfulness and self
      compassion can improve clinicians' sleep and resilience or whether decreasing
      sleep disturbances and building resilience improves mindfulness and compassion.

PMID- 26218888
TI  - Recent Developments in Transplantation and Transfusion Medicine.
AB  - Transplantation and transfusion are related and clinically important areas of
      multidisciplinary expertise, including pre-operative treatment, donor
      recruitment, tissue matching, and post-operative care. We have seen significant
      developments in these areas, especially in the late 20th and early 21st century.
      This paper reviews the latest advances in modern transplantation and transfusion
      medicine, including several new genetic markers (e.g., major histocompatibility
      complex class I chain-related gene A, killer cell immunoglobulin-like receptor,
      and human platelet antigens) for donor and recipient matching, genotyping
      platforms (e.g., next-generation sequencer and Luminex technology), donor
      recruitment strategies, and several clinical applications in which genotyping has
      advantages over agglutination tests (e.g., genotyping of weakly expressed
      antigens and determination of blood groups and human leukocyte antigen types in
      multi-transfused patients). We also highlight the roles of population studies and
      international collaborations in moving towards more efficient donor recruitment
      strategies. 

PMID- 26218889
TI  - Immunomodulation by splenectomy or by FTY720 protects the heart against ischemia
      reperfusion injury.
AB  - The pathogenesis of myocardial ischemia-reperfusion injury (MI/R) involves an
      inflammatory response in the myocardium undergoing reperfusion. Modulation of
      this response by splenectomy constitutes an option to protect the heart from
      MI/R. To mimic the effect of splenectomy in a pharmacological approach, the
      sphingosine-1-phosphate agonist FTY720 was applied at the onset of reperfusion.
      In a closed chest model of MI/R, infarct size was assessed by
      triphenyltetrazolium chloride staining after 1 h of ischemia and 24 h of
      reperfusion, and by Masson trichrome staining 21 days after reperfusion in
      splenectomised mice, mice post-conditioned with FTY720 IP (1 mg/kg), and
      controls. In addition, hemodynamic parameters were recorded after 24 h and 21
      days by catheterization. Infarct size, and immune cell invasion of phagocytic
      monocytes investigated by FACS after 24 h of reperfusion were significantly
      reduced by both splenectomy, and FTY720 treatment. Evaluation after 21 days of
      reperfusion revealed that FTY720 treated animals had an improved hemodynamic
      outcome compared to placebo treated as well as splenectomised animals. FTY720
      treatment reduced cell injury as effectively as splenectomy by lowering the
      number of phagocytic monocytes invading the myocardium and ameliorated
      hemodynamic outcome within the first 21 days. 

PMID- 26218890
TI  - Porcine prion protein amyloid.
AB  - Mammalian prions are composed of misfolded aggregated prion protein (PrP) with
      amyloid-like features. Prions are zoonotic disease agents that infect a wide
      variety of mammalian species including humans. Mammals and by-products thereof
      which are frequently encountered in daily life are most important for human
      health. It is established that bovine prions (BSE) can infect humans while there
      is no such evidence for any other prion susceptible species in the human food
      chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or
      susceptible and resistant pets (cat and dogs, respectively). PrPs from these
      species have been characterized using biochemistry, biophysics and neurobiology.
      Recently we studied PrPs from several mammals in vitro and found evidence for
      generic amyloidogenicity as well as cross-seeding fibril formation activity of
      all PrPs on the human PrP sequence regardless if the original species was
      resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among
      the studied. Experimentally inoculated pigs as well as transgenic mouse lines
      overexpressing porcine PrP have, in the past, been used to investigate the
      possibility of prion transmission in pigs. The pig is a species with
      extraordinarily wide use within human daily life with over a billion pigs
      harvested for human consumption each year. Here we discuss the possibility that
      the largely prion disease resistant pig can be a clinically silent carrier of
      replicating prions. 

PMID- 26218891
TI  - Hyperthyroidism and Hypothyroidism in Male Mice and Their Effects on Bone Mass,
      Bone Turnover, and the Wnt Inhibitors Sclerostin and Dickkopf-1.
AB  - Thyroid hormones are key regulators of bone homeostasis, and Wnt signaling has
      been implicated in thyroid hormone-associated bone loss. Here we tested whether
      hyperthyroidism and hypothyroidism interfere with dickkopf-1 (DKK1) and
      sclerostin, two inhibitors of Wnt signaling. Twelve-week-old male C57BL/6 mice
      were rendered either hyperthyroid or hypothyroid. Hyperthyroid mice displayed
      decreased trabecular (-54%, P < .001) and cortical bone density (-5%, P < .05)
      and reduced cortical thickness (-15%, P < .001), whereas hypothyroid mice showed
      a higher trabecular bone density (+26%, P < .001) with unchanged cortical bone
      parameters. Histomorphometry and biochemical markers of bone remodeling indicated
      high bone turnover in hyperthyroid mice and low bone turnover in hypothyroid
      mice. In vivo, serum DKK1 concentrations were decreased in hyperthyroid mice (
      24%, P < .001) and increased in hypothyroid mice (+18%, P < .01). The increase of
      the number of DKK1-positive cells in hypothyroid mice was confirmed at the tissue
      level. Interestingly, sclerostin was increased in both disease models, although
      to a higher extent in hyperthyroid mice (+50%, P < .001, and +24%, P < .05).
      Serum sclerostin concentrations adjusted for bone mass were increased by 3.3-fold
      in hyperthyroid (P < .001) but not in hypothyroid mice. Consistently, sclerostin
      mRNA expression and the number of sclerostin-positive cells were increased in
      hyperthyroid but not in hypothyroid mice. Our data show that thyroid hormone
      induced changes in bone remodeling are associated with a divergent regulation of
      DKK1 and sclerostin. Thus, the modulation of Wnt signaling by thyroid hormones
      may contribute to thyroid hormone-associated bone disease and altered expression
      of Wnt inhibitors may emerge as potential therapeutic targets. 

PMID- 26218894
TI  - Assessment of Shiga Toxin-Producing Escherichia coli O157 Illnesses Prevented by
      Recalls of Beef Products.
AB  - Beef product recall data from 2005 through 2012 associated with Shiga toxin
      producing Escherichia coli (STEC) O157 contamination were used to develop
      quantitative models to estimate the number of illnesses prevented by recalls. The
      number of illnesses prevented was based on the number of illnesses that occurred
      relative to the number of pounds consumed, then extrapolated to the number of
      pounds of recalled product recovered. A simulation using a Program Evaluation and
      Review Technique (PERT) probability distribution with illness-related recalls
      estimated 204 (95% credible interval, 117-333) prevented STEC O157 illnesses from
      2005 through 2012. Recalls not associated with illnesses had more recalled
      product recovered and prevented an estimated 83 additional STEC O157 illnesses.
      Accounting for underdiagnosis resulted in an estimated total of 7500 STEC O157
      illnesses prevented over 8 years. This study demonstrates that recalls, although
      reactive in nature, are an important tool for averting further exposure and
      illnesses. 

PMID- 26218893
TI  - MicroRNAs in Bone Balance and Osteoporosis.
AB  - Preclinical Research Bone is a rigid and dynamic organ that undergoes continuous
      turnover. Bone homeostasis is maintained by osteoclast-mediated bone resorption
      and osteoblast-mediated bone formation. The interruption of this balance can
      cause various diseases, including osteoporosis a public health issue due to the
      rate of hip fracture, the most serious outcome of osteoporosis. The bone loss in
      osteoporosis results from an increase in bone resorption versus bone formation.
      Thus, regulation of osteoblast and osteoclast activity is a main focus in the
      treatment of osteoporosis. MicroRNAs (miRNAs) are a class of single stranded
      noncoding RNAs consisting of 18-22 nucleotides that have an important role in
      cell differentiation, cell fate, apoptosis, and pathogenesis in various disease
      states. The potential therapeutic and biomarker function of miRNAs in treating
      bone disorders is receiving more attention. The current review summarizes the
      role of miRNAs in bone function at a cellular level in the context of their
      therapeutic potential.

PMID- 26218892
TI  - Theoretical study on the N-demethylation mechanism of theobromine catalyzed by
      P450 isoenzyme 1A2.
AB  - Theobromine, a widely consumed pharmacological active substance, can cause
      undesirable muscle stiffness, nausea and anorexia in high doses ingestion. The
      main N-demethylation metabolic mechanism of theobromine catalyzed by P450
      isoenzyme 1A2 (CYP1A2) has been explored in this work using the unrestricted
      hybrid density functional method UB3LYP in conjunction with the LACVP(Fe)/6-31G
      (H, C, N, O, S, Cl) basis set. Single-point calculations including empirical
      dispersion corrections were carried out at the higher 6-311++G** basis set. Two N
      demethylation pathways were characterized, i.e., 3-N and 7-N demethylations,
      which involve the initial N-methyl hydroxylation to form carbinolamines and the
      subsequent carbinolamines decomposition to yield monomethylxanthines and
      formaldehydes. Our results have shown that the rate-limiting N-methyl
      hydroxylation occurs via a hydrogen atom transfer (HAT) mechanism, which proceeds
      in a spin-selective mechanism (SSM) in the gas phase. The carbinolamines
      generated are prone to decomposition via the contiguous heteroatom-assisted
      proton-transfer. Strikingly, 3-N demethylation is more favorable than 7-N
      demethylation due to its lower free energy barrier and 7-methylxanthine therefore
      is the optimum product reported for the demethylation of theobromine catalyzed by
      CYP1A2, which are in good agreement with the experimental observation. This work
      has first revealed the detail N-demethylation mechanisms of theobromine at the
      theoretical level. It can offer more significant information for the metabolism
      of purine alkaloid. 

PMID- 26218895
TI  - Differentiation-Associated Downregulation of Poly(ADP-Ribose) Polymerase-1
      Expression in Myoblasts Serves to Increase Their Resistance to Oxidative Stress.
AB  - Poly(ADP-ribose) polymerase 1 (PARP-1), the major isoform of the poly (ADP
      ribose) polymerase family, is a constitutive nuclear and mitochondrial protein
      with well-recognized roles in various essential cellular functions such as DNA
      repair, signal transduction, apoptosis, as well as in a variety of
      pathophysiological conditions including sepsis, diabetes and cancer. Activation
      of PARP-1 in response to oxidative stress catalyzes the covalent attachment of
      the poly (ADP-ribose) (PAR) groups on itself and other acceptor proteins,
      utilizing NAD+ as a substrate. Overactivation of PARP-1 depletes intracellular
      NAD+ influencing mitochondrial electron transport, cellular ATP generation and,
      if persistent, can result in necrotic cell death. Due to their high metabolic
      activity, skeletal muscle cells are particularly exposed to constant oxidative
      stress insults. In this study, we investigated the role of PARP-1 in a well
      defined model of murine skeletal muscle differentiation (C2C12) and compare the
      responses to oxidative stress of undifferentiated myoblasts and differentiated
      myotubes. We observed a marked reduction of PARP-1 expression as myoblasts
      differentiated into myotubes. This alteration correlated with an increased
      resistance to oxidative stress of the myotubes, as measured by MTT and LDH
      assays. Mitochondrial function, assessed by measuring mitochondrial membrane
      potential, was preserved under oxidative stress in myotubes compared to
      myoblasts. Moreover, basal respiration, ATP synthesis, and the maximal
      respiratory capacity of mitochondria were higher in myotubes than in myoblasts.
      Inhibition of the catalytic activity of PARP-1 by PJ34 (a phenanthridinone PARP
      inhibitor) exerted greater protective effects in undifferentiated myoblasts than
      in differentiated myotubes. The above observations in C2C12 cells were also
      confirmed in a rat-derived skeletal muscle cell line (L6). Forced overexpression
      of PARP1 in C2C12 myotubes sensitized the cells to oxidant-induced injury. Taken
      together, our data indicate that the reduction of PARP-1 expression during the
      process of the skeletal muscle differentiation serves as a protective mechanism
      to maintain the cellular functions of skeletal muscle during oxidative stress. 

PMID- 26218897
TI  - [Formula: see text]Parent-report and performance-based measures of executive
      function assess different constructs.
AB  - A total of 405 children of 5-18 years of age were administered performance-based
      and parent-report measures of executive function (EF), and measures of motor,
      attention, reading, and mathematics performance. Attention, reading, and
      mathematics abilities were associated with a parent-report measure of EF. Reading
      and mathematics abilities were also associated with performance-based measures of
      EF, including the Animal Sorting, Inhibition, and Response Set subtests of the
      Developmental NEuroPSYchological Assessment-II. In contrast, motor functioning
      was only associated with performance-based measures of EF. Findings suggest that
      different constructs of EF are measured by parent-report versus performance-based
      measures, and that these different constructs of EF are associated with different
      neurodevelopmental processes.

PMID- 26218896
TI  - Comparative and Evolutionary Analysis of the Interleukin 17 Gene Family in
      Invertebrates.
AB  - Interleukin 17 (IL-17) is an important pro-inflammatory cytokine and plays
      critical roles in the immune response to pathogens and in the pathogenesis of
      inflammatory and autoimmune diseases. Despite its important functions, the origin
      and evolution of IL-17 in animal phyla have not been characterized. As determined
      in this study, the distribution of the IL-17 family among 10 invertebrate species
      and 7 vertebrate species suggests that the IL-17 gene may have originated from
      Nematoda but is absent from Saccoglossus kowalevskii (Hemichordata) and Insecta.
      Moreover, the gene number, protein length and domain number of IL-17 differ
      widely. A comparison of IL-17-containing domains and conserved motifs indicated
      somewhat low amino acid sequence similarity but high conservation at the motif
      level, although some motifs were lost in certain species. The third disulfide
      bond for the cystine knot fold is formed by two cysteine residues in
      invertebrates, but these have been replaced by two serine residues in Chordata
      and vertebrates. One third of invertebrate IL-17 proteins were found to have no
      predicted signal peptide. Furthermore, an analysis of phylogenetic trees and exon
      intron structures indicated that the IL-17 family lacks conservation and displays
      high divergence. These results suggest that invertebrate IL-17 proteins have
      undergone complex differentiation and that their members may have developed novel
      functions during evolution. 

PMID- 26218898
TI  - Theoretical Investigation of Obtaining Compounds with Planar Tetracoordinate
      Carbons by Frustrated Lewis Pairs.
AB  - Ten derivatives of 2-borabicyclo[1.1.0]but-1(3)-ene (1a-1j) with different
      degrees of frustration have been investigated using density functional theory.
      Moreover, 1a-1j as Lewis bases were used to form Lewis adducts C3X2BYH/B(C6F5)3
      (2a-2j) with Lewis acid B(C6F5)3. Optimized geometries and the thermodynamic
      properties of giving the Lewis adducts C3X2BYH/B(C6F5)3 reveal that 2a-2j are
      frustrated Lewis pairs (FLPs). Their reactivity of activating H2 and HF show that
      2a-2j are unfavorable to heterolytically cleave H2, whereas 2c-2j can cleave HF
      to form [C3X2BYH](+)[FB(C6F5)3](-). In addition, we found the structures of
      [C3X2BYH](+) in [C3X2BYH](+)[FB(C6F5)3](-) contained a planar tetracoordinate
      carbon (ptC). Therefore, a new method of obtaining main group element compounds
      with ptC by using FLPs was presented. 

PMID- 26218901
TI  - Response to Comment on the article 'Dysplasia epiphysealis hemimelica of the
      knee: an unusual presentation with intra-articular loose bodies and literature
      review' by Wheeldon and Altiok. J Pediatr Orthop B 2015:377-378.

PMID- 26218899
TI  - Successful cross-protective efficacy induced by heat-adapted live attenuated
      nephropathogenic infectious bronchitis virus derived from a natural recombinant
      strain.
AB  - A natural recombinant nephropathogenic K40/09 strain of infectious bronchitis
      virus (IBV) was heat-adapted for possible future use as live attenuated vaccine.
      The K40/09 strain was selected during successive serial passages in specific
      pathogen free (SPF) embryonated eggs at sub-optimal higher temperature (56
      degrees C). Unlike the parental strain, the attenuated strain, designated K40/09
      HP50, was found to be safe in 1-day-old SPF chicks, which showed neither
      mortality nor signs of morbidity, and rarely induced ciliostasis or histological
      changes in the trachea and kidney after intraocular and fine-spray
      administration. K40/09 HP50 provided almost complete protection against two
      distinct subgroups of a nephropathogenic strain (KM91-like and QX-like subgroup)
      and elicited the production of high titers of neutralizing antibody
      (neutralization index of 3.6). We conclude that the K40/09 HP50 vaccine virus is
      rapidly attenuated by heat adaptation and exhibits the desired level of
      attenuation, immunogenicity, and protective efficacy required for a live
      attenuated vaccine. These results indicate that the K40/09 vaccine could be
      helpful for the reduction of economic losses caused by recently emergent
      nephropathogenic IBV infection in many countries. 

PMID- 26218902
TI  - 5,20-Di(pyridin-2-yl)-[28]hexaphyrin(1.1.1.1.1.1): A Stable Huckel Antiaromatic
      Hexaphyrin Stabilized by Intramolecular Hydrogen Bonding and Protonation-Induced
      Conformational Twist To Gain Mobius Aromaticity.
AB  - 5,20-Di(pyridin-2-yl)-[28]hexaphyrin(1.1.1.1.1.1) 7 was prepared and
      characterized as a stable Huckel antiaromatic molecule with a dumbbell-like
      structure stabilized by effective intramolecular hydrogen bonding interactions
      involving the 2-pyridyl nitrogen atoms. Pd(II) metalation of 7 afforded two bis
      Pd(II) complexes, 9-syn and 9-anti, whose structures are rigidly held by Pd(II)
      coordination, rendering 9-syn to be nonaromatic because of its highly distorted
      structure and 9-anti to be Huckel antiaromatic because of its enforced planar
      dumbbell structure. In contrast, protonation of 7 with methanesulfonic acid (MSA)
      led to the formation of its triprotonated species 7H(3), which has been shown to
      take on twisted conformations with Mobius aromaticity in CH(2)Cl(2), while the
      structure was held to be a planar rectangular conformation in the crystal.
      Excited-state dynamics were measured for 7, 7H(3), 9-syn, and 9-anti, which
      indicated their electronic nature to be antiaromatic, aromatic, nonaromatic, and
      antiaromatic, respectively.

PMID- 26218903
TI  - Lens Shape and Refractive Index Distribution in Type 1 Diabetes.
AB  - PURPOSE: To compare lens dimensions and refractive index distributions in type 1
      diabetes and age-matched control groups. METHODS: There were 17 participants with
      type 1 diabetes, consisting of two subgroups (7 young [23 +/- 4 years] and 10
      older [54 +/- 4 years] participants), with 23 controls (13 young, 24 +/- 4 years;
      10 older, 55 +/- 4 years). For each participant, one eye was tested with relaxed
      accommodation. A 3T clinical magnetic resonance imaging scanner was used to image
      the eye, employing a multiple spin echo (MSE) sequence to determine lens
      dimensions and refractive index profiles along the equatorial and axial
      directions. RESULTS: The diabetes group had significantly smaller lens equatorial
      diameters and larger lens axial thicknesses than the control group (diameter mean
      +/- 95% confidence interval [CI]: diabetes group 8.65 +/- 0.26 mm, control group
      9.42 +/- 0.18 mm; axial thickness: diabetes group 4.33 +/- 0.30 mm, control group
      3.80 +/- 0.14 mm). These differences were also significant within each age group.
      The older group had significantly greater axial thickness than the young group
      (older group 4.35 +/- 0.26 mm, young group 3.70 +/- 0.25 mm). Center refractive
      indices of diabetes and control groups were not significantly different. There
      were some statistically significant differences between the refractive index
      fitting parameters of young and older groups, but not between diabetes and
      control groups of the same age. CONCLUSIONS: Smaller lens diameters occurred in
      the diabetes groups than in the age-matched control groups. Differences in
      refractive index distribution between persons with and without diabetes are too
      small to have important effects on instruments measuring axial thickness.

PMID- 26218904
TI  - M2 Macrophages Enhance Pathological Neovascularization in the Mouse Model of
      Oxygen-Induced Retinopathy.
AB  - PURPOSE: To investigate the roles played by M2 macrophages in a mouse model of
      oxygen-induced retinopathy (OIR). METHODS: Oxygen-induced retinopathy was induced
      in C57BL/6J mice by exposing postnatal day seven (P7) pups to 75% oxygen and then
      returning them to room air at P12. Real-time RT-PCR and immunofluorescence
      staining were used to assess the levels and distributions of different macrophage
      markers. Bone marrow-derived M1 and M2 macrophages and mannosylated clodronate
      liposomes (MCLs) were injected into the vitreous on P12 to examine the effects at
      P17. M2 macrophages were cocultured with human retinal endothelial cells (HRECs)
      to examine their effects on proliferation and tube formation. RESULTS: The
      results showed that the M2 macrophages, rather than M1 phenotype, were highly
      expressed in OIR mice. The number of M2 macrophages had increased significantly
      at P17, and the increase was closely associated with the presence of neovascular
      tufts in the OIR retinas. Selective depletion of M2 macrophages suppressed the
      pathological neovascularization and promoted physiological revascularization. In
      contrast, intravitreal injection of bone marrow-derived M2 macrophages or the
      culture supernatants promoted pathological neovascularization and inhibited
      physiological revascularization. In an in vitro coculture system, M2-polarized
      macrophages significantly promoted proliferation and tube formation of HRECs.
      CONCLUSIONS: These results indicated that M2 macrophages, rather than M1, play an
      important role in promoting retinal pathological neovascularization probably by
      producing secreted factors. Thus, targeting M2 macrophages could be a potential
      therapeutic option for inhibiting retinal pathological neovascularization.

PMID- 26218905
TI  - Prevalence of Mitochondrial ND4 Mutations in 1281 Han Chinese Subjects With
      Leber's Hereditary Optic Neuropathy.
AB  - PURPOSE: To investigate the prevalence and spectrum of mitochondrial ND4
      mutations in subjects with Leber's hereditary optic neuropathy (LHON). METHODS: A
      cohort of 1281 Chinese Han probands and 478 control subjects underwent clinical
      and genetic evaluation, and sequence analysis of mitochondrial (mt) DNA, as well
      as enzymatic assay of NADH:ubiquinone oxidoreductase. RESULTS: In this cohort,
      503 probands had a family history of optic neuropathy and 778 subjects were
      sporadic cases. Mutational analysis of ND4 gene identified 149 (102 known and 47
      novel) variants. The prevalence of known m.11778G>A mutation was 35.36%.
      Furthermore, we identified the known m.11696G>A and m.11253T>C mutations and five
      novel putative LHON-associated mutations. These mutations accounted for 2.74% of
      cases of LHON subjects. By enzymatic assay, we showed a mild decrease in the
      activity of NADH:ubiquinone oxidoreductase in mutant cell lines carrying only one
      putative mtDNA mutation. The low penetrance of optic neuropathy and mild
      biochemical defects in these pedigrees carrying only m.11696G>A mutation and one
      putative LHON-associated mutation suggested that the mutation(s) is(are)
      necessary but is(are) itself(themselves) insufficient to produce a visual
      failure. Moreover, mtDNAs in 169 probands carrying the LHON-associated
      mutation(s) were widely dispersed among 13 Eastern Asian haplogroups. In
      particular, the frequencies of haplogroups D, M8, M10, M11, and H in probands
      carrying the LHON-associated mtDNA mutation(s) were higher than those in Chinese
      controls. CONCLUSIONS: These results suggested that the ND4 gene is the hot spot
      for mutations associated with LHON. Thus, these findings may provide valuable
      information for the further understanding of pathogenic mechanism of LHON.

PMID- 26218906
TI  - Fluid Dynamics of a Novel Micro-Fistula Implant for the Surgical Treatment of
      Glaucoma.
AB  - PURPOSE: The purpose of this study was to describe the fluidics of a novel non
      valved glaucoma implant designed to prevent hypotony and compare the fluidics of
      this device with two commonly used non-valved glaucoma devices. METHODS: The XEN
      45 micro-fistula implant was designed to limit hypotony by virtue of its length
      and width according to the Hagen-Poiseuille equation. Flow testing was performed
      using a syringe pump and pressure transducer at multiple flow rates. The pressure
      differentials across the XEN implant, the Ex-Press implant, and 10 mm of silicone
      tubing from a Baerveldt implant at a physiologic flow rate (2.5 MUL/min) were
      extrapolated. RESULTS: The XEN 45 achieved a steady-state pressure calculated at
      7.56 mm Hg at 2.5 MUL/min. At the same flow rate, the Ex-Press device and
      Baerveldt tubing reached steady-state pressures of 0.09 and 0.01 mm Hg,
      respectively. CONCLUSIONS: Under flow testing, the XEN micro-fistula implant was
      able to maintain backpressure above numerical hypotony levels without the use of
      complex valve systems. This is due to the XEN implant's design, derived from the
      principles that dictate Newtonian fluids.

PMID- 26218907
TI  - Three-Dimensional Morphometric Analysis of the Iris by Swept-Source Anterior
      Segment Optical Coherence Tomography in a Caucasian Population.
AB  - PURPOSE: We analyzed by swept-source anterior segment optical coherence
      tomography (SS-ASOCT) the three-dimensional iris morphology in a Caucasian
      population, and correlated the findings with iris color, iris sectors, subject
      age, and sex. METHODS: One eye each from consecutive healthy emmetropic
      (refractive spherical equivalent +/- 3 diopters) volunteers were selected for the
      study. The enrolled eye underwent standardized anterior segment photography to
      assess iris color. Iris images were assessed by SS-ASOCT for volume, thickness,
      width, and pupil size. Sectoral variations of morphometric data among the
      superior, nasal, inferior, and temporal sectors were recorded. RESULTS: A total
      of 135 eyes from 57 males and 78 females, age 49 +/- 17 years, fulfilled the
      inclusion criteria. All iris morphometric parameters varied significantly among
      the different sectors (all P < 0.0001). Iris total volume and thickness were
      significantly correlated with increasingly darker pigmentation (P < 0.0001, P =
      0.0384, respectively). Neither width nor pupil diameter was influenced by iris
      color. Age did not affect iris volume or thickness; iris width increased and
      pupil diameter decreased with age (rs = 0.52, rs = -0.58, respectively). There
      was no effect of sex on iris volume, thickness, or pupil diameter; iris width was
      significantly greater in males (P = 0.007). CONCLUSIONS: Morphology of the iris
      varied by iris sector, and iris color was associated with differences in iris
      volume and thickness. Morphological parameter variations associated with iris
      color, sector, age, and sex can be used to identify pathological changes in
      suspect eyes. To be effective in clinical settings, construction of iris
      morphological databases for different ethnic and racial populations is essential.

PMID- 26218908
TI  - Improving Mobility Performance in Low Vision With a Distance-Based Representation
      of the Visual Scene.
AB  - PURPOSE: Severe visual impairment can have a profound impact on personal
      independence through its effect on mobility. We investigated whether the mobility
      of people with vision low enough to be registered as blind could be improved by
      presenting the visual environment in a distance-based manner for easier detection
      of obstacles. METHODS: We accomplished this by developing a pair of "residual
      vision glasses" (RVGs) that use a head-mounted depth camera and displays to
      present information about the distance of obstacles to the wearer as brightness,
      such that obstacles closer to the wearer are represented more brightly. We
      assessed the impact of the RVGs on the mobility performance of visually impaired
      participants during the completion of a set of obstacle courses. Participant
      position was monitored continuously, which enabled us to capture the temporal
      dynamics of mobility performance. This allowed us to find correlates of obstacle
      detection and hesitations in walking behavior, in addition to the more commonly
      used measures of trial completion time and number of collisions. RESULTS: All
      participants were able to use the smart glasses to navigate the course, and
      mobility performance improved for those visually impaired participants with the
      worst prior mobility performance. However, walking speed was slower and
      hesitations increased with the altered visual representation. CONCLUSIONS: A
      depth-based representation of the visual environment may offer low vision
      patients improvements in independent mobility. It is important for further work
      to explore whether practice can overcome the reductions in speed and increased
      hesitation that were observed in our trial.

PMID- 26218909
TI  - The Association of Estimated Glomerular Filtration Rate With Diabetic Retinopathy
      and Macular Edema.
AB  - PURPOSE: Albuminuria, a marker of diabetic kidney disease, is closely associated
      with diabetic retinopathy (DR) and diabetic macular edema (DME). However, the
      relationship between estimated glomerular filtration rate (eGFR) with DR and DME
      remains unclear, particularly in type 2 diabetes. We investigated the association
      of eGFR with DR and DME in a sample of patients with type 2 diabetes. METHODS: We
      included 263 Caucasian patients with type 2 diabetes aged >= 18 years who
      participated in a clinic-based cross-sectional study in Melbourne, Australia.
      Diabetic retinopathy (n = 140) and DME (n = 61) were assessed from retinal
      photographs graded using the modified Airlie House classification and further
      confirmed with optical coherence tomography. Estimated glomerular filtration
      rate, assessed using the CKD-EPI formula, was analyzed continuously (per SD
      change) and categorically (normal renal function >= 90; impaired renal function,
      60-89, and chronic kidney disease [CKD] < 60 mL/min/1.73 m2). RESULTS: When eGFR
      was analyzed categorically, impaired renal function and CKD were associated with
      the presence of DR when compared to normal renal function in multivariable models
      (odds ratio [OR] with 95% confidence interval [CI] of 2.97 [1.12-7.87] and 3.77
      [1.28-11.10]), respectively. In DR severity analyses, CKD showed significant
      associations with moderate (5.83 [1.44-23.5], P-trend = 0.02) and severe DR (4.91
      [1.26-19.0], P-trend = 0.04). These associations persisted when eGFR was analyzed
      continuously (P = 0.04). No significant associations were found between eGFR and
      DME. CONCLUSIONS: Our results suggest that lower levels of eGFR were associated
      with the presence and severity of DR, but not with DME.

PMID- 26218910
TI  - In Vivo Assessment of Pharmacologic Vitreolysis in Rabbits With the Digital
      Fluoroscopy System.
AB  - PURPOSE: The purpose of this study was to demonstrate the efficacy of the digital
      fluoroscopy system (DFS) for the in vivo assessment of pharmacologically induced
      posterior vitreous detachment (PVD) and vitreous liquefaction in a rabbit model.
      METHODS: Twenty eyes from 10 New Zealand white rabbits were divided into 5
      groups. In each group, one rabbit received an intravitreal injection of 2.0 U
      plasmin in the right eye and 0.5 U plasmin in the left eye. Intravitreal
      injection of 0.1 mL balanced salt solution (BSS) was given in the right eye, and
      no injection was given in the left eye of another rabbit used as a control.
      Intraocular fluid dynamics were assessed by the DFS, using a contrast agent in
      each group at different time intervals (6 hours, 12 hours, 1 day, 3 days, and 7
      days). After rabbits were killed, both eyes were enucleated. Scanning electron
      microscopy was used to confirm the morphological alterations of the vitreoretinal
      interface as observed in the DFS. RESULTS: Complete PVD was observed after 12
      hours with 2.0 U plasmin injection, whereas complete PVD was observed only after
      3 days in eyes injected with 0.5 U plasmin. Eyes that received BSS injection or
      did not receive an injection failed to show complete PVD even after 7 days.
      Complete vitreous liquefaction was observed after 7 days with 2.0 U plasmin
      injection, but no eyes with 0.5 U plasmin or BSS injection showed complete
      liquefaction. We could clearly confirm the presence of PVD and the degree of
      vitreous liquefaction by using DFS. CONCLUSIONS: Digital fluoroscopy system
      appears to be a useful tool for the evaluation of pharmacological vitreolysis in
      rabbits with clear in vivo visualization of PVD and vitreous liquefaction.

PMID- 26218912
TI  - Influence of Opa1 Mutation on Survival and Function of Retinal Ganglion Cells.
AB  - PURPOSE: Mutations in the OPA1 gene cause autosomal dominant optic atrophy
      (ADOA), a visual disorder associated with degeneration of retinal ganglion cells
      (RGCs). Here, we characterized the disease progression in a homologous mouse
      model B6;C3-Opa1 329-355del and asked whether the pronounced cell death affects
      certain RGC types more than others. METHODS: The influence of the Opa1 mutation
      was assessed by morphologic (retina and optic nerve histology) and functional
      (multielectrode array) methods. RESULTS: The RGC loss of approximately 50% within
      18 months was significantly more pronounced in RGCs with small-caliber axons.
      Small-caliber axon RGCs comprise a variety of functional RGC types. Accordingly,
      electrophysiological analyses of RGCs did not show a dropout of distinct
      functional RGC subgroups. However, the response properties of RGCs were affected
      significantly by the mutation. Surprisingly, these functional changes were
      different under different luminance conditions (scotopic, mesopic, and photopic).
      Finally, melanopsin cells are known to be less susceptible to retinal insults. We
      found that these cells are also spared in the Opa1 mouse model, and demonstrated
      for the first time that this resistance persisted even when the melanopsin gene
      had been knocked-out. CONCLUSIONS: Small-caliber axons show a higher
      vulnerability to the Opa1 mutation in our mouse model for ADOA. Luminance
      dependent functional changes suggest an influence of the Opa1 mutation on the
      retinal circuitry upstream of RGCs. Photoresponsive RGCs are protected against
      cell death due to the Opa1 mutation, but not by melanopsin expression itself.

PMID- 26218911
TI  - Birc7: A Late Fiber Gene of the Crystalline Lens.
AB  - PURPOSE: A distinct subset of genes, so-called "late fiber genes," is expressed
      in cells bordering the central, organelle-free zone (OFZ) of the lens. The
      purpose of this study was to identify additional members of this group. METHODS:
      Fiber cells were harvested from various layers of the lens by laser micro
      dissection and subjected to microarray, in situ hybridization, and Western blot
      analysis. RESULTS: Expression of Livin, a member of the inhibitor of apoptosis
      protein (IAP) family encoded by Birc7, was strongly upregulated in deep cortical
      fiber cells. The depth-dependent distribution of Livin mRNA was confirmed by
      quantitative PCR and in situ hybridization. The onset of Livin expression
      coincided with loss of organelles from primary fiber cells. Livin expression
      peaked at 1 month but was sustained even in aged lenses. Antibodies raised
      against mouse Livin labeled multiple bands on immunoblots, reflecting progressive
      proteolysis of the parent molecule during differentiation. Mice harboring a
      floxed Birc7 allele were generated and used to conditionally delete Birc7 in
      lens. Lenses from knockout mice grew normally and retained their transparency,
      suggesting that Livin does not have an indispensable role in fiber cell
      differentiation. CONCLUSIONS: Birc7 is a late fiber gene of the mouse lens. In
      tumor cells, Livin acts as an antiapoptotic protein, but its function in the lens
      is enigmatic. Livin is a RING domain protein with putative E3 ubiquitin ligase
      activity. Its expression in cells bordering the OFZ is consistent with a role in
      organelle degradation, a process in which the ubiquitin proteasome pathway has
      been implicated previously.

PMID- 26218913
TI  - A New Splicing Isoform of Cacna2d4 Mimicking the Effects of c.2451insC Mutation
      in the Retina: Novel Molecular and Electrophysiological Insights.
AB  - PURPOSE: Mutations in CACNA2D4 exon 25 cause photoreceptor dysfunction in humans
      (c.2406C->A mutation) and mice (c.2451insC mutation). We investigated the
      feasibility of an exon-skipping therapeutic approach by evaluating the splicing
      patterns and functional role of targeted exons. METHODS: Splicing of the targeted
      alpha2delta4 (CACNA2D4) exons in presence and absence of the mutation was
      assessed by RT-PCR in vivo on mouse retinae and in vitro in HEK293T cells using
      splicing-reporter minigenes. Whole-cell patch-clamp recordings were performed to
      evaluate the impact of different Cacna2d4 variants on the biophysical properties
      of Cav1.4 L-type calcium channels (CACNA1F). RESULTS: Splicing analysis revealed
      the presence of a previously unknown splicing isoform of alpha2delta4 in the
      retina that truncates the gene open reading frame (ORF) in a similar way as the
      c.2451insC mutation. This isoform originates from alternative splicing of exon 25
      (E25) with a new exon (E25b). Moreover, the c.2451insC mutation has an effect on
      splicing and increases the proportion of transcripts including E25b. Our
      electrophysiological analyses showed that only full-length alpha2delta4 was able
      to increase Cav1.4/beta3-mediated currents while all other alpha2delta4 variants
      did not mediate such effect. CONCLUSIONS: The designed exon-skipping strategy is
      not applicable because the resulting skipped alpha2delta4 are nonfunctional.
      alpha2delta4 E25b splicing variant is normally present in mouse retina and mimics
      the effect of c.2451insC mutation. Since this variant does not promote
      significant Cav1.4-mediated calcium current, it could possibly mediate a
      different function, unrelated to modulation of calcium channel properties at the
      photoreceptor terminals.

PMID- 26218914
TI  - Trinucleotide Repeat Expansion in the TCF4 Gene in Fuchs' Endothelial Corneal
      Dystrophy in Japanese.
AB  - PURPOSE: The purpose of this study was to evaluate the association between the
      intronic expansion of a trinucleotide repeat (TNR) in the TCF4 gene and Fuchs'
      endothelial corneal dystrophy (FECD) in a Japanese population. METHODS: Forty
      seven Japanese FECD patients and 96 age-matched controls were recruited. FECD
      patients and controls were examined by slit-lamp and noncontact specular
      microscopy. The repeat length was determined by direct sequencing and short
      tandem repeat assay of PCR-amplified DNA and Southern blotting of unamplified
      DNA. RESULTS: A TNR expansion, defined as >50 CTG repeats in the TCF4 gene was
      identified in 12 of 47 FECD cases (26%) and 0 of 96 controls (0%; P < 0.001).
      Sensitivity and specificity in this study were 26% and 100%, respectively. The
      clinical characteristics of FECD patients with TNR expansion were not distinct
      from those without TNR expansion. CONCLUSIONS: These findings show for the first
      time in a Japanese population the association of the TNR expansion in TCF4 with
      FECD. In contrast to Caucasian cohorts in whom the TNR expansion is present in
      most patients with FECD, a CTG expansion is present in a minority of Japanese
      subjects, indicating other genetic variants as common causes of phenotypically
      identical disease in this population.

PMID- 26218915
TI  - Assessment of Proteins Associated With Complement Activation and Inflammation in
      Maculae of Human Donors Homozygous Risk at Chromosome 1 CFH-to-F13B.
AB  - PURPOSE: To determine the effects of chromosome 1 genotype and cigarette smoking
      on levels of complement activation and inflammation in the human macula. METHODS:
      Donor macular tissue was stratified into three groups by diplotype at the AMD
      associated CFH-to-F13B locus: homozygous "risk" (n = 9, 56-78 years), homozygous
      neutral (n = 2, 64-79 years), and homozygous "protective" (n = 6, 61-78 years)
      diplotype. Importantly, all donors were homozygous nonrisk at the ARMS2/HTRA1
      locus, so that purely chromosome 1-directed pathways were examined.
      Immunohistochemistry was performed by using 14 antibodies, mostly against markers
      of complement and inflammation, followed by confocal microscopy and
      immunofluorescence quantification (all masked to donor status). RESULTS: Donors
      homozygous risk at CFH-to-F13B exhibited significantly higher levels of terminal
      complement complex (TCC) in macular Bruch's membrane (BM; P = 0.03),
      choriocapillaris (CC; P = 0.04), and choriocapillaris intercapillary septa (CC
      IS; P = 0.03), compared to homozygous protected donors. Smoking was associated
      with increased TCC in BM (P = 0.05), CC IS (P = 0.03), and choroidal stroma (CS;
      P = 0.01), and with substantially elevated C-reactive protein (CRP) levels in RPE
      (P = 0.04), BM (P = 0.01), CC (P = 0.05), and CS (P = 0.05). Smoking was
      associated with higher levels of oxidative stress in macular RPE (P = 0.04) and
      CS (P = 0.01). CONCLUSIONS: Genetic risk at the CFH-to-F13B locus was associated
      with higher levels of complement activation at the human macular RPE-choroid
      interface, as was cigarette smoking. Levels of CRP were substantially elevated in
      risk donors with smoking history. Examination of human macular tissue from donors
      with "pure" diplotypes allows assessment of AMD-associated pathways driven solely
      by CFH-to-F13B. These findings have important implications for identifying
      chromosome 1-directed pathways and therapeutic targets.

PMID- 26218916
TI  - Synthesis, molecular orbital, optical and device characterization of mononuclear
      mixed ligand nickel(II) complex of phthalate with N,N,N',N'
      tetramethylethylenediamine for photodiode applications.
AB  - In this work, a new synthesized mononuclear mixed ligand nickel(II) complex was
      characterized by various techniques. Crystalline characteristics of
      [Ni(Phth)(Me4en)(H2O)2].4H2O were studied by using transmission electron
      microscope(TEM). Well crystalline structure corresponds to the hexagonal crystal
      system and identified by selected area electron diffraction (SAED) were achieved.
      Coordination of the nickel(II) ion with the functional groups of the ligands was
      established from the IR spectrum. Molar conductance of the current complex in DMF
      (10(-3)mol/L) indicated a non-electrolytic nature of the complex. Electronic
      spectra showed a strong band in the region 661-684nm; MeCN (661nm), CHCl3
      (663nm), MeOH (667nm), Me2CO (675nm), DMSO (682nm) and DMF (684nm) which can be
      assigned to (3)A2g(F)->(3)T1g(F) transition of an octahedral structure around
      nickel(II). Multiple peaks were easily resolved from the spectral dependence of
      the absorption coefficient (alpha) measurements and the analysis near the
      fundamental absorption edge showed two direct allowed transition with energy gaps
      of 1.18 and 2.53eV. Dark current-voltage and capacitance-voltage characteristics
      of [Ni(Phth)(Me4en)(H2O)2].4H2O/n-Si heterojunctions were studied to extract the
      main important parameters of the heterojunction device. The electrical
      characteristics of the heterojunction device under illumination hold the
      suitability of the device for optoelectronic applications.

PMID- 26218917
TI  - Synthesis, crystal structure, biological activity and theoretical calculations of
      novel isoxazole derivatives.
AB  - Series of isoxazole derivatives were synthesized by substituted chalcones and 2
      chloro-6-fluorobenzene formaldehyde oxime with 1,3-dipolar cycloaddition. The
      target compounds were determined by melting point, IR, (1)H NMR, elemental
      analyses and HRMS. The crystal structure of compound 3a was detected by X-ray
      diffraction and it crystallizes in the triclinic space group p2(1)/c with z=4.
      The molecular geometry of compound 3a was optimized using density functional
      theory (DFT/B3LYP) method with the 6-31G+(d,p) basis set in the ground state.
      From the optimized geometry of the molecule, FT-IR, FT-Raman, HOMO-LUMO and
      natural bond orbital (NBO) were calculated at B3LYP/6-31G+(d,p) level. Finally,
      the antifungal activity of the synthetic compounds were evaluated against Pythium
      solani, Gibberella nicotiancola, Fusarium oxysporium f.sp. niveum and Gibberella
      saubinetii.

PMID- 26218918
TI  - Response surface methodology approach for optimization of adsorption of Janus
      Green B from aqueous solution onto ZnO/Zn(OH)2-NP-AC: Kinetic and isotherm study.
AB  - The Janus Green B (JGB) adsorption onto homemade ZnO/Zn(OH)2 nanoparticles loaded
      on activated carbon (AC) which characterized by FESEM and XRD analysis has been
      reported. Combination of response surface methodology (RSM) and central composite
      design (CCD) has been employed to model and optimize variables using STATISTICA
      10.0 software. The influence of parameters over pH (2.0-8.0), adsorbent (0.004
      0.012g), sonication time (4-8min) and JGB concentration (3-21mgL(-1)) on JGB
      removal percentage was investigated and their main and interaction contribution
      was examined. It was revealed that 21mgL(-1) JGB, 0.012g ZnO/Zn(OH)2-NP-AC at pH
      7.0 and 7min sonication time permit to achieve removal percentage more than 99%.
      Finally, a good agreement between experimental and predicted values after 7min
      was achieved using pseudo-second-order rate equation. The Langmuir adsorption is
      appropriate for correlation of equilibrium data. The small amount of adsorbent
      (0.008-0.015g) is applicable for successful removal of JGB (RE>99%) in short time
      (7min) with high adsorption capacity (81.3-98.03mgg(-1)).

PMID- 26218919
TI  - Is There a Correlation Between Footstep Length, Lower Extremities, and Stature?
AB  - A probable correlation between stature and footstep length is expected, and
      consequently, the stature may be estimated from footstep length. The present
      research was conducted to study the correlation of footstep length with length of
      the lower extremities and stature. The study participants (n=142) were asked to
      walk on a paper sheet with inked feet and footstep length was measured. Mean
      stature and lower limb length were significantly larger in males. Sex differences
      were not observed in the average footstep length. Average footstep length and
      lower limb length did not show a significant correlation among the participants.
      A statistically significant correlation was observed between average footstep
      length and stature only among females. Our observations suggest that the length
      of the lower limb may not be a major factor in determining the footstep length of
      a person and that the forensic utility of stature estimation from footstep length
      may be limited.

PMID- 26218921
TI  - Patient charges for health services: the opinions of healthcare stakeholders in
      Bulgaria.
AB  - The reforms of the Bulgarian healthcare sector have been widely discussed, both
      nationally and internationally. In spite of the reforms, problems with the
      efficiency, equity and quality in healthcare provision continue to exist in
      Bulgaria. Among others, the reforms included the implementation of formal patient
      charges for the use of healthcare services. These were established in the country
      in 2000. Formal patient charges are applied to all levels of medical services
      with the exception of emergency care. The aim of this paper is to describe and
      analyze the attitudes of Bulgarian healthcare stakeholders toward patient
      charges. The analysis is based on data collected in focus group discussions and
      in-depth interviews carried out in Bulgaria in May-June 2009. The paper concludes
      by recommendations for policies related to patient payments. The social
      sensitivity of these payments requires broad discussion before policy decisions
      are implemented. There is also a need of a well-thought communication strategy on
      the issue of patient payments by the Ministry of Health.

PMID- 26218922
TI  - Sulfate Local Coordination Environment in Schwertmannite.
AB  - Schwertmannite, a nanocrystalline ferric oxyhydroxy-sulfate mineral, plays an
      important role in many environmental geochemical processes in acidic sulfate-rich
      environments. The sulfate coordination environment in schwertmannite, however,
      remains unclear, hindering our understanding of the structure, formation, and
      environmental behavior of the mineral. In this study, sulfur K-edge X-ray
      absorption near edge structure (XANES) and extended X-ray absorption fine
      structure (EXAFS) spectroscopic analyses in combination with infrared
      spectroscopy were used to determine the sulfate local atomic environment in wet
      and air-dried schwertmannite samples after incubation at various pHs and ionic
      strengths. Results indicate that sulfate exists as both inner- and outer-sphere
      complexes in schwertmannite. Regardless of the sample preparation conditions, the
      EXAFS-determined S-Fe interatomic distances are 3.22-3.26 A, indicative of
      bidentate-binuclear sulfate inner-sphere complexes. XANES spectroscopy shows that
      the proportion of the inner-sphere complexes decreases with increasing pH for
      both wet and dried samples and that the dried samples contain much more inner
      sphere complexes than the wet ones at any given pH. Assuming that schwertmannite
      is a distorted akaganeite-like structure, the sulfate inner-sphere complexation
      suggests that, the double chains of the edge-sharing Fe octahedra, enclosing the
      tunnel, must contain defects, on which reactive singly-Fe coordinated hydroxyl
      functional groups form for ligand exchange with sulfate. The drying effect
      suggests that the tunnel contains readily exchangeable H2O molecules in addition
      to sulfate ions. 

PMID- 26218924
TI  - Drug-interactions of azole antifungals with selected immunosuppressants in
      transplant patients: strategies for optimal management in clinical practice.
AB  - The management of drug-drug interactions (DDIs) between azole antifungals
      (fluconazole, itraconazole, posaconazole and voriconazole) and immunosuppressants
      (cyclosporine, tacrolimus, everolimus and sirolimus) in transplant patients
      remains challenging, as the impact of altered immunosuppressant concentrations
      puts the patient at high risk for either toxicity or transplant rejection. As a
      result, it is a complex task for the clinician to maintain immunosuppressant
      concentrations within the desired therapeutic range and this requires a highly
      individualized patient approach. We provide important tools for adequate
      assessment of the drug interactions that cause this pharmacokinetic variability
      of immunosuppressants. A stepwise approach for the evaluation and subsequent
      management options, including a decision flow chart, are provided for optimal
      handling of these clinically relevant DDIs. 

PMID- 26218925
TI  - Clinical Specimen-Direct LAMP: A Useful Tool for the Surveillance of blaOXA-23
      Positive Carbapenem-Resistant Acinetobacter baumannii.
AB  - Healthcare-associated infections are a leading cause of morbidity and mortality
      worldwide. Treatment is increasingly complicated by the escalating incidence of
      antimicrobial resistance. Among drug-resistant pathogens, carbapenem-resistant
      Acinetobacter baumannii (CRAb) is of increasing concern because of the limited
      applicable therapies and its expanding global distribution in developed countries
      and newly industrialized countries. Therefore, a rapid detection method that can
      be used even in resource-poor countries is urgently required to control this
      global public health threat. Conventional techniques, such as bacterial culture
      and polymerase chain reaction (PCR), are insufficient to combat this threat
      because they are time-consuming and laborious. In this study, we developed a loop
      mediated isothermal amplification (LAMP) method for detecting blaOXA-23-positive
      CRAb, the most prevalent form of CRAb in Asia, especially in Thailand, and
      confirmed its efficacy as a surveillance tool in a clinical setting. Clinical
      samples of sputum and rectal swabs were collected from patients in a hospital in
      Bangkok and used for LAMP assays. After boiling and centrifugation, the
      supernatants were used directly in the assay. In parallel, a culture method was
      used for comparison purposes to evaluate the specificity and sensitivity of LAMP.
      As a first step, a total of 120 sputum samples were collected. The sensitivity of
      LAMP was 88.6% (39/44), and its specificity was 92.1% (70/76) using the culture
      method as the "gold standard". When surveillance samples including sputum and
      rectal swabs were analyzed with the LAMP assay, its sensitivity was 100.0%. This
      method enables the direct analysis of clinical specimens and provides results
      within 40 minutes of sample collection, making it a useful tool for surveillance
      even in resource-poor countries. 

PMID- 26218920
TI  - Functional imaging of the lungs with gas agents.
AB  - This review focuses on the state-of-the-art of the three major classes of gas
      contrast agents used in magnetic resonance imaging (MRI)-hyperpolarized (HP) gas,
      molecular oxygen, and fluorinated gas--and their application to clinical
      pulmonary research. During the past several years there has been accelerated
      development of pulmonary MRI. This has been driven in part by concerns regarding
      ionizing radiation using multidetector computed tomography (CT). However, MRI
      also offers capabilities for fast multispectral and functional imaging using gas
      agents that are not technically feasible with CT. Recent improvements in gradient
      performance and radial acquisition methods using ultrashort echo time (UTE) have
      contributed to advances in these functional pulmonary MRI techniques. The
      relative strengths and weaknesses of the main functional imaging methods and gas
      agents are compared and applications to measures of ventilation, diffusion, and
      gas exchange are presented. Functional lung MRI methods using these gas agents
      are improving our understanding of a wide range of chronic lung diseases,
      including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in
      both adults and children.

PMID- 26218927
TI  - A novel benzene quantitative analysis method using miniaturized metal ionization
      gas sensor and non-linear bistable dynamic system.
AB  - In this paper, a novel benzene quantitative analysis method utilizing
      miniaturized metal ionization gas sensor and non-linear bistable dynamic system
      was investigated. Al plate anodic gas-ionization sensor was installed for
      electrical current-voltage data measurement. Measurement data was analyzed by non
      linear bistable dynamics system. Results demonstrated that this method realized
      benzene concentration quantitative determination. This method is promising in
      laboratory safety management in benzene leak detection. 

PMID- 26218926
TI  - Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody
      Responses to All Four Viral Serotypes.
AB  - Dengue virus (DENV) infection is a major emerging disease widely distributed
      throughout the tropical and subtropical regions of the world affecting several
      millions of people. Despite constants efforts, no specific treatment or effective
      vaccine is yet available. Here we show a novel design of a DNA immunisation
      strategy that resulted in the induction of strong antibody responses with high
      neutralisation titres in mice against all four viral serotypes. The immunogenic
      molecule is an engineered version of the domain III (DIII) of the virus E protein
      fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII
      sequences were also codon-optimised for expression in mammalian cells. While DIII
      alone is very poorly secreted, the codon-optimised fusion protein is rightly
      expressed, folded and secreted at high levels, thus inducing strong antibody
      responses. Mice were immunised using gene-gun technology, an efficient way of
      intradermal delivery of the plasmid DNA, and the vaccine was able to induce
      neutralising titres against all serotypes. Additionally, all sera showed
      reactivity to a recombinant DIII version and the recombinant E protein produced
      and secreted from mammalian cells in a mono-biotinylated form when tested in a
      conformational ELISA. Sera were also highly reactive to infective viral particles
      in a virus-capture ELISA and specific for each serotype as revealed by the low
      cross-reactive and cross-neutralising activities. The serotype specific sera did
      not induce antibody dependent enhancement of infection (ADE) in non-homologous
      virus serotypes. A tetravalent immunisation protocol in mice showed induction of
      neutralising antibodies against all four dengue serotypes as well. 

PMID- 26218928
TI  - Dynamic roles of p53-mediated metabolic activities in ROS-induced stress
      responses.
AB  - The p53 tumor suppressor is a multifaceted polypeptide that impedes tumorigenesis
      by regulating a diverse array of cellular processes. Triggered by a wide variety
      of stress stimuli, p53 transcriptionally regulates genes involved in the
      canonical tumor suppression pathways of apoptosis, cell-cycle arrest, and
      senescence. We recently discovered a novel mechanism whereby p53 inhibits cystine
      uptake through repression of the SLC7A11 gene to mediate ferroptosis.
      Importantly, this p53-SLC7A11 axis is preserved in the p53(3KR) mutant, and
      contributes to its ability to suppress tumorigenesis in the absence of the
      classical tumor suppression mechanisms. Here, we report that wild type p53 can
      induce both apoptosis and ferroptosis upon reactive oxygen species (ROS)-induced
      stress. Furthermore, we demonstrate that p53's functional N-terminal domain is
      required for its capacity to regulate oxidative stress responses and ferroptosis.
      Notably, activated p53 dynamically modulates intracellular ROS, causing an
      initial reduction and a subsequent increase of ROS levels. Taken together, these
      data implicate ferroptosis as an additional component of the cell death program
      induced by wild type p53 in human cancer cells, and reveal a complex and dynamic
      role of p53 in oxidative stress responses. 

PMID- 26218929
TI  - Generational Solidarity in Europe and Israel.
AB  - This study explored various dimensions of generational relationships between
      older parents and their adult children using the second wave of SHARE (Survey of
      Health, Ageing and Retirement in Europe), comparing it to Dykstra's and Fokkema's
      (2011) analyses of the first wave. Results were further compared to the OASIS
      study (Old Age and Autonomy: The Role of Service Systems and Intergenerational
      Solidarity). The intergenerational solidarity model served as the main conceptual
      framework. Analyses yielded four family relationship types present in all
      countries, albeit with different frequencies. Around half of the respondents in
      the 11 countries were identified with close ties and flow of support. Four
      conclusions were drawn: (1) importance of personal resources; (2) cultural
      differences and meanings for families; (3) highlighting within-country
      difference; and (4) strength of intergenerational solidarity. The importance of
      understanding generational relationships in the current era with higher longevity
      and changing family structures is emphasized and explicated.

PMID- 26218930
TI  - Clinicopathologic features associated with efficacy and long-term survival in
      metastatic melanoma patients treated with BRAF or combined BRAF and MEK
      inhibitors.
AB  - BACKGROUND: The degree of response and the duration of survival of patients
      treated with mitogen-activated protein kinase (MAPK) inhibitors are highly
      variable. Whether baseline clinicopathologic factors can predict the clinical
      course with treatment is largely unknown. METHODS: For 142 consecutive
      immunotherapy- and MAPK inhibitor-naive patients with BRAF-mutant metastatic
      melanoma who were treated during clinical trials with BRAF inhibitors (n = 111)
      or a combination of dabrafenib and trametinib (n = 31), clinicopathologic factors
      were correlated with the response to MAPK inhibitors and survival. RESULTS: The
      median follow-up was 15.7 months (range, 0.6-60.5 months). The 2-, 3-, and 4-year
      overall survival (OS) rates were 43%, 24%, and 24%, respectively. A multivariate
      analysis demonstrated that the only clinicopathologic factors associated with
      longer progression-free survival (PFS) and OS were female sex and a normal
      pretreatment serum lactate dehydrogenase (LDH) level. The BRAF V600E genotype and
      an absence of primary melanoma ulceration were also independently associated with
      longer PFS but not OS. The median OS was 23.5 months for patients with normal LDH
      levels and 7.3 months for those with elevated LDH levels (hazard ratio, 0.31; P <
      .001). Complete responders had the best survival, but disease progression still
      occurred in 2 of 7 patients. CONCLUSIONS: Long-term survival occurs for a
      minority of patients receiving MAPK inhibitor treatment alone. Sex, serum LDH,
      BRAF genotype, and primary melanoma ulceration status are independent factors
      associated with treatment outcomes. Patients with a complete response to
      treatment have the best survival, but relapses still occur.

PMID- 26218931
TI  - Peripheral arterial disease in patients with giant cell arteritis: a meta
      analysis.
AB  - AIM: To investigate the association between giant cell arteritis (GCA) and risk
      of peripheral arterial disease (PAD). METHODS: We conducted a systematic review
      and meta-analysis of observational cohort studies that reported relative risks,
      hazard ratios or standardized incidence ratios with 95% confidence comparing PAD
      risk in patients with GCA versus non-GCA subjects. Pooled risk ratios and 95%
      confidence intervals were calculated using a random-effect, generic inverse
      variance of DerSimonian and Laird. RESULTS: Four studies with 9789 patients with
      GCA and 236 728 controls were identified and included in our data analysis. The
      pooled risk ratio of PAD among patients with GCA compared with controls was 1.88
      (95% CI 1.04-3.41). The statistical heterogeneity was high with an I(2) of 89%.
      CONCLUSION: Our study demonstrated a statistically significant increased risk of
      PAD among patients with GCA.

PMID- 26218932
TI  - Layer-by-Layer Proteomic Analysis of Mytilus galloprovincialis Shell.
AB  - Bivalve shell is a biomineralized tissue with various layers/microstructures and
      excellent mechanical properties. Shell matrix proteins (SMPs) pervade and envelop
      the mineral crystals and play essential roles in biomineralization. Despite that
      Mytilus is an economically important bivalve, only few proteomic studies have
      been performed for the shell, and current knowledge of the SMP set responsible
      for different shell layers of Mytilus remains largely patchy. In this study, we
      observed that Mytilus galloprovincialis shell contained three layers, including
      nacre, fibrous prism, and myostracum that is involved in shell-muscle attachment.
      A parallel proteomic analysis was performed for these three layers. By combining
      LC-MS/MS analysis with Mytilus EST database interrogations, a whole set of 113
      proteins was identified, and the distribution of these proteins in different
      shell layers followed a mosaic pattern. For each layer, about a half of
      identified proteins are unique and the others are shared by two or all of three
      layers. This is the first description of the protein set exclusive to nacre,
      myostracum, and fibrous prism in Mytilus shell. Moreover, most of identified
      proteins in the present study are novel SMPs, which greatly extended
      biomineralization-related protein data of Mytilus. These results are useful, on
      one hand, for understanding the roles of SMPs in the deposition of different
      shell layers. On the other hand, the identified protein set of myostracum
      provides candidates for further exploring the mechanism of adductor muscle-shell
      attachment. 

PMID- 26218933
TI  - MiDAS ENCORE: Randomized Controlled Study Design and Protocol.
AB  - BACKGROUND: Epidural steroid injections (ESIs) are commonly used for treatment of
      symptomatic lumbar spinal stenosis (LSS). ESIs are generally administered after
      failure of conservative therapy. For LSS patients suffering from neurogenic
      claudication, the mild(r) procedure provides an alternative to ESIs via minimally
      invasive lumbar decompression. Both ESIs and mild offer interventional pain
      treatment options for LSS patients experiencing neurogenic claudication
      refractory to more conservative therapies. STUDY DESIGN: Prospective, multi
      center, randomized controlled, clinical study. SETTING: Twenty-six interventional
      pain management centers throughout the United States. OBJECTIVE: To compare
      patient outcomes following treatment with either mild or ESIs in LSS patients
      with neurogenic claudication and having verified ligamentum flavum hypertrophy.
      METHODS: Study participants include Medicare beneficiaries who meet study
      inclusion/exclusion criteria. Eligible patients will be randomized in a 1:1 ratio
      to one of 2 treatment arms, mild (treatment group) or ESI (control group). Each
      study group will include approximately 150 patients who have experienced
      neurogenic claudication symptoms for >= 3 months duration who have failed to
      respond to physical therapy, home exercise programs, and oral analgesics. Those
      randomized to mild are prohibited from receiving lumbar ESIs during the study
      period, while those randomized to ESI may receive ESIs up to 4 times per year.
      Patient assessments will occur at baseline, 6 months, and one year. An additional
      assessment will be conducted for the mild patient group at 2 years. OUTCOME
      MEASURES: The primary efficacy outcome measure is the proportion of Oswestry
      Disability Index (ODI) responders from baseline to one year follow-up in the
      treatment group (mild) versus the control group (ESI). ODI responders are defined
      as those patients achieving the validated Minimal Important Change (MIC) of >= 10
      point improvement in ODI from baseline to follow-up as a clinically significant
      efficacy threshold. Secondary efficacy outcome measures include the proportion of
      Zurich Claudication Questionnaire (ZCQ) and Numeric Pain Rating Scale (NPRS)
      responders from baseline to follow-up using validated MIC thresholds. Improvement
      in ZCQ domains of >= 0.5 is considered significant, and a Patient Satisfaction
      score of at least 2.5 represents a satisfied patient. A reduction of >= 2 points
      in NPRS is considered significant pain relief. The primary safety outcome measure
      is the incidence of device- and/or procedure-related adverse events. RESULTS:
      Descriptive summaries will be presented by randomized group for all outcome
      measures at baseline and follow-up time points. Inferential statistical analysis
      will be conducted to determine significant differences related to functional
      improvement, pain relief, and safety outcomes. Primary study results will be
      presented based on one-year follow-up data, with an interim analysis report when
      6-month follow-up data become available. LIMITATIONS: Patients are not blinded
      due to significant differences in treatment protocols between study groups. Also,
      since neither study arm is focused on treatment of radicular pain, there may be a
      higher non-responder rate for both groups versus standard of care due to study
      restrictions on adjunctive pain therapies. CONCLUSIONS: This prospective, multi
      center, randomized controlled study will provide Level I evidence of the safety
      and effectiveness of mild versus ESIs in managing neurogenic claudication
      symptoms in LSS patients.

PMID- 26218934
TI  - Anatomical Flow Pattern of Contrast in Lumbar Epidural Space: A Human Study with
      a Midline vs. Parasagittal Interlaminar Approach under Fluoroscopy.
AB  - BACKGROUND: Epidural injections for managing chronic back pain are one of the
      most commonly performed interventions; however, controversy continues regarding
      the most effective method of epidural injections. A ventral distribution of
      epidural injected drug plays a significant role in its effectiveness. OBJECTIVE:
      To determine the distribution of a drug in the epidural space after parasagital
      and midline epidural injection. SETTING: Academic hospital. STUDY DESIGN: In
      randomized double-blind clinical trial, patients with a diagnosis of low back
      pain (LBP) and unilateral lumbosacral radicular pains were randomized to receive
      drug through either parasagital or midline approach. METHODS: Patients were
      assessed for anterior epidural spread of contrast under fluoroscopy in
      anteroposterior and lateral views. After epidural space confirmation,
      triamcinolone (80 mg) plus bupivacain was injected and patients were followed up
      for 2 weeks. RESULTS: Fifty-six patients enrolled in the study. Successful
      infiltration of the drug into the ventral epidural space was successfully
      achieved in 75% of cases in the parasagital group but in only 25% of the cases in
      using a midline approach. Effective pain relief (numeric rating scale [NRS] < 3)
      was observed in 76.5% of patients in the parasagital group and 24.5% of patients
      in the midline group (P = 0.001) at 2 weeks. Number of patients with improved
      disability (measured by Oswestry Disability Index [ODI] < 20%) was significantly
      higher in the parasagital group (78%) compared to the midline group (26%) at 2
      weeks (P = 0.002). LIMITATIONS: The results of the current study should be
      interpreted in relation to the study design and future studies should include
      larger patient numbers and longer follow-up time. However, the results are
      consistent with previous studies. CONCLUSION: Parasagital epidural injection
      showed higher infiltration of the drug to the ventral epidural space compared to
      the midline approach. The higher infiltration of the ventral epidural space
      provides better improvement of clinical disability and pain in the parasagital
      group.

PMID- 26218935
TI  - Whitacre Needle Reduces the Incidence of Intravascular Uptake in Lumbar
      Transforaminal Epidural Steroid Injections.
AB  - BACKGROUND: Transforaminal epidural steroid injection (TFESI) is a commonly used
      interventional pain management procedures to treat radicular leg pain. Although
      most reported complications of TFESI are minor, serious morbidity has also been
      demonstrated including spinal cord infarction, paraplegia, and quadriparesis.
      Suggested mechanisms include direct vascular injury or intravascular injection of
      particulate steroid. OBJECTIVE: We compared 2 different needle types, Whitacre
      and Quincke type needles, with regard to intravascular injection rate with total
      procedure time and the amount of radiation during lumbar TFESI. STUDY DESIGN:
      Prospective, randomized trial. SETTING: An interventional pain management
      practice in South Korea. METHODS: After Institutional Review Board approval, 149
      patients undergoing lumbar TFESI for radicular leg pain were randomly assigned to
      one of 2 needle groups (Whitacre needle or Quincke type needle). After final
      confirmation of intravascular injection with digital subtraction angiography,
      total procedure time and amount of radiation exposure during TFESI were measured.
      RESULTS: The overall incidence of intravascular injection was 10.4% (28/269). We
      analyzed the overall incidence of intravascular injection according to the 2
      different needle types. The incidence of intravascular injection of the Whitacre
      needle was 5.4% (8/146), whereas the incidence of intravascular injection of the
      Quincke needle was 16.2% (20/123). Total procedure time and amount of radiation
      required to complete the TFESI in the Whitacre and Quincke needle groups was
      168.4 +/- 57.9 (seconds) and 33.4 +/- 15.9 (cGy/cm2), 131.9 +/- 46.0 (seconds)
      and 33.2 +/- 15.8 (cGy/cm2), respectively. LIMITATIONS: The physician who
      performed the TFESI was not blinded to the type of needle for detecting
      intravascular injection. This study was focused on lumbar TFESI, however, most
      TFESIs are performed at the L4-5 or L5-S1 level. CONCLUSION: The Whitacre needle
      had the benefit of reducing the incidence of intravascular injection with minimal
      differences in technical difficulties and the amount of radiation exposure during
      lumbar TFESI.

PMID- 26218936
TI  - Palpation Versus Ultrasound-Guided Acromioclavicular Joint Intra-articular
      Corticosteroid Injections: A Retrospective Comparative Clinical Study.
AB  - BACKGROUND: Primary osteoarthritis (OA) is the most common cause of pain arising
      from the acromioclavicular (AC) joint. The true incidence is unknown because of
      differences in the criteria used to define arthritis in various studies. The
      proper diagnosis of AC joint OA requires a thorough physical examination,
      radiographic findings, and a diagnostic local anesthetic injection. OBJECTIVE:
      The goal of this study was to assess the effects and safety of ultrasound (US)
      versus palpation-guided acromioclavicular (AC) joint intra-articular (IA)
      corticosteroid injection for patients with osteoarthritis (OA) of the AC joint.
      STUDY DESIGN: Retrospective, compared clinical study. SETTING: University
      hospital outpatient pain clinic. METHOD: We retrospectively reviewed the charts
      of patients with AC joint degenerative OA who had undergone US or palpation
      guided AC joint IA corticosteroid injection between January 2012 and December
      2013 at our outpatient clinic. One hundred consecutive patients identified from
      chart review met inclusion criteria. Patients (N = 50) in US guide AC joint IA
      steroid injection group were administered a mixture of 0.5% lidocaine (1 mL) with
      triamcinolone (20 mg/mL; 0.5 mL) and radiographic contrast material (0.5 mL) and
      patients (N = 50) in palpation-guided AC joint IA steroid injection group were
      administered a mixture of 0.5% lidocaine (1 mL) with triamcinolone (20 mg/mL; 0.5
      mL) and 0.5 mL of radiographic contrast material. Results were measured using the
      Shoulder Pain and Disability Index (SPADI), Verbal Numeric pain Scale (VNS) at
      rest (VNSar), under local pressure (VNSlp) ,and the arm adduction test (VNSaat)
      at the joint space area before injections and at one, 3, and 6 months after the
      injections. Successful treatment occurred when patients obtained significant pain
      relief (as measured by > 50% improvement in the VNS score and 20 point
      improvement in the SPADI) at one, 3, and 6 months after the injections.
      Univariable analysis was performed to evaluate the relationship between possible
      outcome predictors and therapeutic effect by using a chi-square test. Logistic
      regression analysis was performed to assess whether injection method, injection
      accuracy, patients' age, gender, and duration of the disease were independent
      predictors of successful outcome. RESULTS: SPADI, VNSaat, VNSlp, and VNSar
      improved at one, 3, and 6 months after the injections in both groups. There was a
      statistically significantly greater improvement in the VNSlp score and SPDAI at 6
      months and in the VNSaat score at 3 months and 6 months for US-guided group as
      compared with the palpation group. Successful treatment is defined as significant
      differences found between the groups or from the 3-month to 6-month outcomes.
      Multiple logistic regression and univariable analysis showed that the significant
      outcome predictors at 6-month follow-up was the injection accuracy. LIMITATIONS:
      Limitations include the retrospective nature of the study, lack of evaluation of
      long-term effects , most of the injections were performed in patients with a BMI
      of less than 30 kg/m2, and the treatment procedures were conducted by the same
      physician. CONCLUSION: US-guided AC joint IA injection for the treatment of
      symptomatic AC joint OA resulted in better pain and functional status improvement
      than palpation-guided IA injection at the 6-month follow-up.

PMID- 26218937
TI  - Thoracic Epidural Blood Patches in the Treatment of Spontaneous Intracranial
      Hypotension: A Retrospective Case Series.
AB  - BACKGROUND: Spontaneous intracranial hypotension (SIH) results from leaks
      developing in the dura mater. The major symptom is orthostatic headache which
      gradually disappears after lying down. Lumbar epidural blood patches (EBPs) can
      be effective in relieving headaches, however, thoracic and cervical EBPs have
      also been applied to alleviate the symptoms. OBJECTIVE AND METHODS: Retrospective
      collection of the main characteristics of SIH, site and amount of blood
      injection, and clinical outcomes of 18 patients who underwent thoracic EBPs for
      intractable SIH. STUDY DESIGN: Retrospective case series RESULTS: All thoracic
      autologous EBPs except 3 were performed in the sitting position. Patients
      undergoing epidural puncture at lower thoracic levels (T10-T12) received 25 mL of
      autologous blood, 15 mL and 18 mL were injected at spinal segments T5-T7 (mid
      thoracic) and T2-T4 (upper- thoracic), respectively. Thoracic EBPs did not lead
      to immediate resolution of symptoms in 3 of 18 patients; one of them underwent
      early repetition with complete headache relief, one refused a second EBP, and one
      experienced partial resolution, followed by a recurrence, and then satisfactory
      improvement with a second high thoracic EBP. In long-term follow-up only 2
      patients complained of symptoms or relapses. LIMITATIONS: Retrospective nature of
      the case series, single center experience. CONCLUSIONS: Performing thoracic
      targeted EBPs as the preferred approach theoretically improves results with
      respect to those observed with lumbar EBPs. The immediate response was comparable
      with that of other reports, but the long-term success rate (90%) turned out to be
      very effective in terms of both quality of headache relief and very low incidence
      of recurrence.

PMID- 26218938
TI  - Rationale for Prospective Assays of Intrathecal Mixtures Including Morphine,
      Ropivacaine and Ziconotide: Prevention of Adverse Events and Feasibility in
      Clinical Practice.
AB  - BACKGROUND: Use of intrathecal admixtures is widespread, but compounding these is
      sometimes challenging and may result in errors and complications causing super
      potency or sub potency adverse events in patients or malfunctions in the pump
      itself. OBJECTIVE: The purpose of this study is to evaluate the accuracy of
      compounding of intrathecal admixtures through a prospective, systematic
      quantitative analysis of each component of the mixture before delivery to
      patients. STUDY DESIGN: Observational follow up prospective study of intrathecal
      mixtures components concentrations before refills. SETTINGS: Assays were
      performed on all intrathecal admixtures produced by the ICO-Paul Papin
      compounding pharmacy between January 2013 and October 2014 using Ultra High
      Performance Liquid Chromatography (U.H.P.L.C.). In addition, pH levels of
      admixtures have been measured since June 2014. When measured concentrations were
      15% above or below the required concentrations, the mixture was excluded and
      compounded again. RESULTS: 1729 mixtures were analyzed. Mean deviation from
      theoretical values was -1.17% +/- 0.28% for morphine, -0.95% +/- 1.07% for
      ropivacaine, and 4.82% +/- 0.6% for ziconotide. Exclusion rates were 8.33%
      overall, but fell from 11.67% in 2013 to 4.97% in 2014. Most exclusions were
      caused by inaccuracy in the dose of ziconotide. Average mixture pH of the 603
      tested admixtures was 4.83 +/- 0.6%. LIMITATIONS: This study is monocentric and
      limitations include also its non-randomized nature with no clinical comparison of
      the rate of adverse events with a refill process without control of each
      component concentrations. CONCLUSION: Prospective assays provide benefits in
      ensuring accuracy of intrathecal mixture compounding and in preventing overdosing
      or sub dosing, most notably concerning Ziconotide.

PMID- 26218939
TI  - Full-Endoscopic Technique Discectomy Versus Microendoscopic Discectomy for the
      Surgical Treatment of Lumbar Disc Herniation.
AB  - BACKGROUND: Full-endoscopic technique discectomy (FED) or microendoscopic
      discectomy (MED) are 2 widely used minimally invasive procedures for the
      treatment of lumbar disc herniation. However, there is insufficient literature
      regarding the differences between these 2 surgical procedures. OBJECTIVE: To
      compare the clinical outcomes of 2 different minimally invasive methods--full
      endoscopic technique discectomy and microendoscopic discectomy--in the surgical
      treatment of lumbar disc herniation. STUDY DESIGN: Retrospective study. SETTING:
      Inpatient surgery center. METHODS: Data form 65 patients with lumbar disc
      herniation treated with one of 2 minimally invasive procedures were
      retrospectively analyzed. Patients were divided into 2 groups according to
      surgical method: the FED group (n = 35) and the MED group (n = 30). Surgery time,
      time kept in bed after surgery, duration of postoperative hospital stay, visual
      analog scale (VAS; 0-10), and Oswestry Disability index (ODI; 0-100%) were
      assessed and compared between the 2 groups. RESULTS: There were no significant
      differences in the preoperative data between the 2 groups (P > 0.05). VAS and ODI
      scores improved significantly postoperatively in both groups (P < 0.05). Surgery
      time was longer in the FED group than in the MED group (P < 0.05). However, the
      FED group was superior to the MED group, with less time in bed, shorter hospital
      stay, and lower VAS scores one day postoperatively (P < 0.05). There were no
      significant differences in VAS or ODI scores at one, 3, and 12 months after
      surgery between the 2 groups (P > 0.05). LIMITATIONS: This is a retrospective
      study with a relatively short follow-up period. CONCLUSIONS: Although the
      clinical outcomes of the 2 surgical techniques were similar, the FED had the
      advantages of quicker postoperative recovery and more immediate effect.

PMID- 26218940
TI  - Sympathetic Block as a New Treatment for Lymphedema.
AB  - BACKGROUND: Breast cancer-related lymphedema (BCRL) not only has physical
      implications, but also affects the quality of life in breast cancer survivors.
      Despite numerous studies of various therapies, the optimal treatment for BCRL is
      unknown. OBJECTIVE: In this study, we investigated the efficacy of sympathetic
      blockade (thoracic sympathetic ganglion block, [TSGB]) in treating BCRL. STUDY
      DESIGN: Retrospective study. SETTING: Tertiary referral center/teaching hospital.
      METHODS: TSGB was performed in 35 patients under fluoroscopic guidance. First,
      arm circumference and Lymphedema and Breast Cancer Questionnaire [LBCQ] score
      were assessed before TSGB and 2 weeks and 2 months after the procedure. Efficacy
      was defined as a >= 50% reduction in the LBCQ score and a >= 50% decrease in the
      circumference difference between the unaffected and affected arms 2 months after
      TSGB. Second, TSGB efficacy according to the lymphedema stage and the period
      between BCRL onset and TSGB (< 6 months vs. > 6 months) was evaluated. RESULTS:
      The arm circumference and LBCQ score significantly decreased at 2 months (P <
      0.001), and 65.7% of patients showed good efficacy. Patients with high stage
      lymphedema showed improved efficacy after TSGB compared to those with low stage
      disease (P = 0.045). The TSGB efficacy did not differ according to the period
      between BCRL onset and TSGB. LIMITATIONS: This study was not a randomized
      prospective controlled study and did not compare the therapeutic outcomes to
      those in a conservative treatment group. CONCLUSIONS: TSGB in BCRL patients
      appears to be effective in decreasing the affected arm circumference. TSGB may be
      an alternative option in BCRL patients who do not respond to conservative
      therapy.

PMID- 26218941
TI  - Comparison between Balloon Kyphoplasty and Short Segmental Fixation Combined with
      Vertebroplasty in the Treatment of Kummell's Disease.
AB  - BACKGROUND: Kummell's disease is a clinical syndrome characterized by a minor
      spinal trauma with a symptom-free period from months to years, followed by
      progressive painful kyphosis. Kyphoplasty and vertebroplasty have been introduced
      to treat Kummell's disease, and obtained good clinical results. Recently, delayed
      cement displacement was reported for Kummell's disease treated by cement
      augmentation alone. Some authors recommended internal fixation combined with
      cement injection for this particular condition. OBJECTIVE: To evaluate and
      compare the clinical efficacy, especially the pain reduction, of 2 procedures
      (kyphoplasty alone versus short segmental fixation combined with vertebroplasty)
      in the treatment of Kummell's disease. STUDY DESIGN: Retrospective evaluation and
      comparison of postoperative VAS scores and radiographic outcomes. SETTING: Single
      center inpatient population. METHODS: Two procedures, including conventional
      balloon kyphoplasty and short segmental fixation combined with vertebroplasty,
      were utilized for 54 patients with Kummell's disease. All patients were followed
      up for 8-42 months. Visual analog scale (VAS), vertebral height, and local
      kyphotic angle were evaluated and compared for 2 groups before surgery, after
      surgery, and at final follow-up. Pearson correlation coefficients were calculated
      to assess the relationship between the decreased values of pain scores (VAS) and
      improvement of anterior vertebral height and local kyphotic angle. RESULTS: For
      the KP group, the VAS pain score decreased significantly from 7.8 +/- 0.9 before
      surgery to 3.3 +/- 1.0 after surgery (P < 0.01), and 2.9 +/- 0.9 at final follow
      up (P < 0.01). The mean height of the anterior vertebral body increased from 14.8
      +/- 2.4 mm before surgery to 19.3 +/- 2.1 mm after surgery (P < 0.01). The mean
      local kyphotic angle decreased from 22.7 +/- 6.9 degrees  before surgery to 14.5
      +/- 5.3 degrees  after surgery (P < 0.01). For SSF + VP group, the VAS pain score
      decreased significantly from 7.2 +/- 1.6 before surgery to 4.7 +/- 1.3 after
      surgery (P < 0.01), and 3.5 +/- 1.2 at final follow-up (P < 0.01). The mean
      height of the anterior vertebral body increased from 13.6 +/- 2.5mm before
      surgery to 17.3 +/- 2.7 mm after surgery (P < 0.01). The mean local kyphotic
      angle decreased from 24.7 +/- 9.2 degrees  before surgery to 15.5 +/- 6.2 degrees
      after surgery (P < 0.01). No significant loss of correction of vertebral height
      and kyphosis was observed at follow-up. Improvement of VAS score had no
      correlation with improvement of vertebral height or local kyphotic angle.
      Asymptomatic cement leakage occurred in both groups. LIMITATIONS: Retrospective
      study with a relatively small sample size. CONCLUSIONS: This study showed that
      both balloon kyphoplasty alone and short segmental fixation combined with
      vertebroplasty for Kummell's disease were safe and effective. Improvement of VAS
      score had no correlation with improvement of vertebral height or local kyphotic
      angle. Comparatively, balloon kyphoplasty resulted in same the clinical outcomes
      with less complications.

PMID- 26218942
TI  - Plasma Exchange Therapy in Patients with Complex Regional Pain Syndrome.
AB  - BACKGROUND: Complex regional pain syndrome (CRPS) is a severe chronic pain
      condition that most often develops following trauma. Some investigators have
      postulated CRPS to be a post-traumatic neuralgia associated with distal
      degeneration of small-diameter peripheral axons. Intravenous immunoglobulin
      treatment (IVIG) has been shown to be efficacious in the treatment of painful
      polyneuropathies. Some CRPS patients have been reported to respond to IVIG. Based
      on a recent hypothesis proposing an autoimmune etiology for CRPS, we decided to
      offer plasma exchange therapy (PE) to CRPS patients with a clinical presentation
      suggestive of a small fiber neuropathy. OBJECTIVES: To evaluate the efficacy of
      PE in a group of CRPS patients with a clinical presentation suggestive of a small
      fiber neuropathy that were either non-responders or poor responders to their
      current treatment. STUDY DESIGN: This is a retrospective case series study of
      CRPS patients that met the Budapest diagnostic criteria for CRPS and received PE
      as treatment for their illness between September 2012 and June 2014. Approval for
      this review was granted by the Drexel University Institutional Review Board.
      SETTING: Drexel University College of Medicine pain clinic METHODS: Thirty-three
      CRPS patients that received PE treatment were retrospectively studied. The workup
      for these patients consisted of a complete medical and pain evaluation, the
      completion of the short-form McGill questionnaire, quantitative sensory testing
      (QST), and skin punch biopsy. The PE protocol was as follows: all patients had a
      series of PE therapies (range 5 to 11 with a mean of 7.2) performed over a 2 to 3
      week period. Following the PE series, the patients had a pain evaluation and
      completed the short-form McGill questionnaire. Patients that responded to PE were
      offered maintenance therapy consisting of either weekly PE or other immune
      modulating agents. In these patients, their pain was evaluated during the
      maintenance phase. RESULTS: Thirty of the 33 patients demonstrated significant (P
      < 0.01) median pain reduction of 64% following the initial series of PE. Three
      patients demonstrated no improvement. Twenty-four patients are receiving
      maintenance therapy, the pain reduction in these patients following the initial
      PE series has been maintained with either weekly PE (n = 15), oral immune
      modulating agents (n = 8), or IVIG (n = 1). The remaining 6 patients are not
      receiving maintenance therapy and their pain has returned to pre-treatment
      levels. In addition, this study suggests that patients with the greatest loss of
      small fibers and the greatest temperature sensory deficits are most likey to
      benefit from PE therapy. LIMITATIONS: The major limitation of this study is its
      retrospective nature which includes non-randomization, non-blinding, and an
      uncontrolled design. CONCLUSIONS: This study shows that PE is effective in a
      subset of patients with severe long-standing CRPS and that the reduction in pain
      following the initial series of PE treatments can be maintained on a weekly PE
      schedule, IVIG, or with other immune modulating drugs. Large, randomized, placebo
      controlled studies may be required to confirm and expand these results. Such
      studies may lead to new therapies for this severe life-altering condition.

PMID- 26218943
TI  - Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review.
AB  - BACKGROUND: Serotonin syndrome is a mild to potentially life-threatening syndrome
      associated with excessive serotonergic activity within the central nervous
      system. Serotonin syndrome is associated with medication use, drug interactions,
      and overdose. While serotonin syndrome is often associated with the use of
      selective serotonin inhibitors (SSRI), an increasing number of reports are being
      presented involving the use of tramadol. METHODS: This review article contains an
      overview of serotonin syndrome while specifically looking at tramadol's
      pharmacology and risk factors for serotonin syndrome. With tramadol's increasing
      popularity, the goal of this article is to make physicians more alert and aware
      of this potential side effect associated with tramadol. CONCLUSIONS: In
      conclusion, with the increasing incidence of serotonin syndrome, prescribing
      physicians should be aware of and educate their patients on the potential side
      effects of tramadol. It is important that the prescribing physician reviews
      patient medications for concurrent serotonergic drugs and monitors for potential
      abuse.

PMID- 26218944
TI  - In Errata.

PMID- 26218945
TI  - Celebrating the Life of Alon P. Winnie, MD, Regional Anesthesia and Pain
      Management Icon.

PMID- 26218946
TI  - The Tragedy of the Implementation of ICD-10-CM as ICD-10: Is the Cart Before the
      Horse or Is There a Tragic Paradox of Misinformation and Ignorance?
AB  - The forced implementation of ICD-10-CM (International Classification of Diseases,
      Tenth Revision, Clinical Modification) codes that are specific to the United
      States, scheduled for implementation October 1, 2015, which is vastly different
      from ICD-10 (International Classification of Diseases, Tenth Revision),
      implemented worldwide, which has 14,400 codes, compared to ICD-10-CM with 144,000
      codes to be implemented in the United States is a major concern to practicing
      U.S. physicians and a bonanza for health IT and hospital industry. This
      implementation is based on a liberal interpretation of the Health Insurance
      Portability and Accountability Act (HIPAA), which requires an update to ICD-9-CM
      (International Classification of Diseases, Ninth Revision, Clinical Modification)
      and says nothing about ICD-10 or beyond. On June 29, 2015, the Supreme Court
      ruled that the Environmental Protection Agency unreasonably interpreted the Clean
      Air Act when it decided to set limits on the emissions of toxic pollutants from
      power plants, without first considering the costs on the industry. Thus, to do so
      is applicable to the medical industry with the Centers for Medicare and Medicaid
      Services (CMS) unreasonably interpreting HIPAA and imposing existent extensive
      regulations without considering the cost. In the United States, ICD-10-CM with a
      10-fold increase in the number of codes has resulted in a system which has become
      so complicated that it no longer compares with any other country. Moreover, most
      WHO members use the ICD-10 system (not ICD-10-CM) only to record mortality in 138
      countries or morbidity in 99 countries. Currently, only 10 countries employ ICD
      10 (not ICD-10-CM) in the reimbursement process, 6 of which have a single payer
      health care system. Development of ICD-10-CM is managed by 4 non-physician
      groups, known as cooperating parties. They include the Centers for Disease
      Control and Prevention (CDC), CMS, the American Hospital Association (AHA), and
      the American Health Information Management Association (AHIMA). The AHIMA has
      taken the lead with the AHA just behind, both with escalating profits and
      influence, essentially creating a statutory monopoly for their own benefit.
      Further, the ICD-10-CM coalition includes 3M which will boost its revenues and
      profits substantially with its implementation and Blue Cross Blue Shield which
      has its own agenda. Physician groups are not a party to these cooperating parties
      or coalitions, having only a peripheral involvement. ICD-10-CM creates numerous
      deficiencies with 500 codes that are more specific in ICD-9-CM than ICD-10-CM.
      The costs of an implementation are enormous, along with maintenance costs,
      productivity, and cash disruptions.

PMID- 26218947
TI  - A Best-Evidence Systematic Appraisal of the Diagnostic Accuracy and Utility of
      Facet (Zygapophysial) Joint Injections in Chronic Spinal Pain.
AB  - BACKGROUND: Spinal zygapophysial, or facet, joints are a source of axial spinal
      pain and referred pain in the extremities. Conventional clinical features and
      other noninvasive diagnostic modalities are unreliable in diagnosing
      zygapophysial joint pain. STUDY DESIGN: A systematic review of the diagnostic
      accuracy of spinal facet joint nerve blocks. OBJECTIVE: To determine the
      diagnostic accuracy of spinal facet joint nerve blocks in chronic spinal pain.
      METHODS: A methodological quality assessment of included studies was performed
      using Quality Appraisal of Reliability Studies (QAREL). Only diagnostic accuracy
      studies meeting at least 50% of the designated inclusion criteria were utilized
      for analysis. The level of evidence was classified as Level I to V based on the
      grading of evidence utilizing best evidence synthesis. Data sources included
      relevant literature identified through searches of PubMed and other electronic
      searches published from 1966 through March 2015, Cochrane reviews, and manual
      searches of the bibliographies of known primary and review articles. OUTCOME
      MEASURES: Studies must have been performed utilizing controlled local anesthetic
      blocks. The criterion standard must have been at least 50% pain relief from
      baseline scores and the ability to perform previously painful movements. RESULTS:
      The available evidence is Level I for lumbar facet joint nerve blocks with the
      inclusion of a total of 17 studies with dual diagnostic blocks, with at least 75%
      pain relief with an average prevalence of 16% to 41% and false-positive rates of
      25% to 44%. The evidence for diagnosis of cervical facet joint pain with cervical
      facet joint nerve blocks is Level II based on a total of 11 controlled diagnostic
      accuracy studies, with significant variability among the prevalence in a
      heterogenous population with internal inconsistency. The prevalence rates ranged
      from 36% to 67% with at least 80% pain relief as the criterion standard and a
      false-positive rate of 27% to 63%. The level of evidence for the diagnostic
      accuracy of thoracic facet joint nerve blocks is Level II with 80% or higher pain
      relief as the criterion standard with a prevalence ranging from 34% to 48% and
      false-positive rates ranging from 42% to 48%. LIMITATIONS: The shortcomings of
      this systematic review include a paucity of literature related to the thoracic
      spine, continued debate on an appropriate gold standard, appropriateness of
      diagnostic blocks, and utility. CONCLUSION: The evidence is Level I for the
      diagnostic accuracy of lumbar facet joint nerve blocks, Level II for cervical
      facet joint nerve blocks, and Level II for thoracic facet joint nerve blocks in
      assessment of chronic spinal pain.

PMID- 26218948
TI  - A Systematic Review and Best Evidence Synthesis of the Effectiveness of
      Therapeutic Facet Joint Interventions in Managing Chronic Spinal Pain.
AB  - BACKGROUND: The therapeutic spinal facet joint interventions generally used for
      the treatment of axial spinal pain of facet joint origin are intraarticular facet
      joint injections, facet joint nerve blocks, and radiofrequency neurotomy. Despite
      interventional procedures being common as treatment strategies for facet joint
      pathology, there is a paucity of literature investigating these therapeutic
      approaches. Systematic reviews assessing the effectiveness of various therapeutic
      facet joint interventions have shown there to be variable evidence based on the
      region and the modality of treatment utilized. Overall, the evidence ranges from
      limited to moderate. OBJECTIVE: To evaluate and update the clinical utility of
      therapeutic lumbar, cervical, and thoracic facet joint interventions in managing
      chronic spinal pain. STUDY DESIGN: A systematic review of therapeutic lumbar,
      cervical, and thoracic facet joint interventions for the treatment of chronic
      spinal pain. METHODS: The available literature on lumbar, cervical, and thoracic
      facet joint interventions in managing chronic spinal pain was reviewed. The
      quality assessment criteria utilized were the Cochrane Musculoskeletal Review
      Group criteria and Interventional Pain Management Techniques-Quality Appraisal of
      Reliability and Risk of Bias Assessment (IPM-QRB) for randomized trials and
      Interventional Pain Management Techniques-Quality Appraisal of Reliability and
      Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for observational
      studies. The level of evidence was classified at 5 levels from Level I to Level
      V. Data sources included relevant literature identified through searches on
      PubMed and EMBASE from 1966 through March 2015, and manual searches of the
      bibliographies of known primary and review articles. OUTCOME MEASURES: The
      primary outcome measure was pain relief (short-term relief = up to 6 months and
      long-term > 6 months). Secondary outcome measures were improvement in functional
      status, psychological status, return to work, and reduction in opioid intake
      consumption. RESULTS: A total of 21 randomized controlled trials meeting
      appropriate inclusion criteria were assessed in this evaluation. A total of 5
      observational studies were assessed. In the lumbar spine, for long-term
      effectiveness, there is Level II evidence for radiofrequency neurotomy and lumbar
      facet joint nerve blocks, whereas the evidence is Level III for lumbosacral
      intraarticular injections. In the cervical spine, for long-term improvement,
      there is Level II evidence for cervical radiofrequency neurotomy and cervical
      facet joint nerve blocks, and Level IV evidence for cervical intraarticular
      injections. In the thoracic spine there is Level II evidence for thoracic facet
      joint nerve blocks and Level IV evidence for radiofrequency neurotomy for long
      term improvement. LIMITATIONS: The limitations of this systematic review include
      an overall paucity of high quality studies and more specifically the lack of
      investigations related to thoracic facet joint injections. CONCLUSION: Based on
      the present assessment for the management of spinal facet joint pain, the
      evidence for long-term improvement is Level II for lumbar and cervical
      radiofrequency neurotomy, and therapeutic facet joint nerve blocks in the
      cervical, thoracic, and lumbar spine; Level III for lumbar intraarticular
      injections; and Level IV for cervical intraarticular injections and thoracic
      radiofrequency neurotomy.

PMID- 26218949
TI  - Pathogenesis, Diagnosis, and Treatment of Cervical Vertigo.
AB  - Cervical vertigo is characterized by vertigo from the cervical spine. However,
      whether cervical vertigo is an independent entity still remains controversial. In
      this narrative review, we outline the basic science and clinical evidence for
      cervical vertigo according to the current literature. So far, there are 4
      different hypotheses explaining the vertigo of a cervical origin, including
      proprioceptive cervical vertigo, Barre-Lieou syndrome, rotational vertebral
      artery vertigo, and migraine-associated cervicogenic vertigo. Proprioceptive
      cervical vertigo and rotational vertebral artery vertigo have survived with time.
      Barre-Lieou syndrome once was discredited, but it has been resurrected recently
      by increased scientific evidence. Diagnosis depends mostly on patients'
      subjective feelings, lacking positive signs, specific laboratory examinations and
      clinical trials, and often relies on limited clinical experiences of clinicians.
      Neurological, vestibular, and psychosomatic disorders must first be excluded
      before the dizziness and unsteadiness in cervical pain syndromes can be
      attributed to a cervical origin. Treatment for cervical vertigo is challenging.
      Manual therapy is recommended for treatment of proprioceptive cervical vertigo.
      Anterior cervical surgery and percutaneous laser disc decompression are effective
      for the cervical spondylosis patients accompanied with Barre-Lieou syndrome. As
      to rotational vertebral artery vertigo, a rare entity, when the exact area of the
      arterial compression is identified through appropriate tests such as magnetic
      resonance angiography (MRA), computed tomography angiography (CTA) or digital
      subtraction angiography (DSA) decompressive surgery should be the chosen
      treatment.

PMID- 26218950
TI  - Do Acute and Chronic Pain Patients Differ on Affirmation of One Aspect of Pain
      Acceptance? Acknowledgement that a Cure Is Unlikely.
AB  - BACKGROUND: Many chronic pain patients (CPPs) cannot be cured of their pain, but
      can learn to manage it. This has led to research on pain "acceptance" which is
      defined as a behavior pattern with awareness of pain but not directed at changing
      pain. OBJECTIVE: CPPs who have accepted their pain generally acknowledge that a
      cure is unlikely. Time with pain may be necessary to reach such an
      acknowledgment. It was therefore hypothesized that fewer acute pain patients
      (APPs) than CPPs should affirm that a cure is unlikely and that other described
      aspects of acceptance such as denial of disability status should be associated
      with cure is unlikely in both APPs and CPPs. STUDY DESIGN: APPs and CPPs were
      compared for frequency of endorsement of 2 items/questions with face validity for
      cure is unlikely: little hope of getting better from pain (LH) and physical
      problem (pain) can't be cured (CBC). Demographic variables and variables reported
      associated with acceptance were utilized in logistic prediction models for the
      above items in APPs and CPPs. SETTING: Rehabilitation programs/offices. RESULTS:
      CPPs were statistically more likely than APPs to affirm both LH and CBC. In both
      APPs and CPPs, items reported associated with acceptance, e.g., denial of
      disability status, predicted LH and CBC. LIMITATIONS: Information gathered from
      CPP self-reports. CONCLUSIONS: APPs versus CPPs differ on their affirmation on
      acknowledgement that a cure is unlikely.

PMID- 26218951
TI  - Prescription Opioid Use, Harms and Interventions in Canada: A Review Update of
      New Developments and Findings since 2010.
AB  - BACKGROUND: Canada has featured the second-highest levels of prescription opioid
      (PO) use globally behind the United States, and reported extensive PO-related
      harms (e.g., non-medical PO use [NMPOU], PO-related morbidity and mortality). A
      recent comprehensive review synthesized key data on PO use, PO-related harms, and
      interventions in Canada, yet a substantive extent of new studies and data have
      emerged. OBJECTIVE: To conduct and present a comprehensive review update on PO
      use, PO-related harms, and interventions in Canada since 2010. STUDY DESIGN:
      Narrative review METHODS: We conducted literature searches, employing pertinent
      keywords, in key databases, focusing on PO-related studies/data in/for Canada
      since 2010, or pertinent studies/data from earlier periods not included in our
      previous review. In addition, we identified relevant data from "grey" literature
      (e.g., government, survey, other data or system reports). Relevant data were
      screened and extracted, and categorized into 4 main sections of indicators: 1) PO
      dispensing and use, 2) non-medical PO use, 3) PO-related morbidity/mortality, 4)
      PO-related interventions and impacts. RESULTS: PO-dispensing in Canada overall
      continued to increase and/or remain at high levels in Canada from 2010 to 2013,
      with the exception of the province of Ontario where marked declines occurred
      starting in2012; quantitative and qualitative PO dispensing patterns continued to
      vary considerably between provinces. Several studies identified common "high PO
      dosing" prescribing practices in different settings. Various data suggested
      declining NMPOU levels throughout most general (e.g., adult, students), yet not
      in special risk (e.g., street drug users, First Nations) populations. While
      treatment demand in Ontario plateaued, rising PO-related driving risks as well as
      neo-natal morbidity were identified by different studies. PO-related mortality
      was measured to increase--in total numbers and proportionally--in various
      Canadian jurisdictions. Select reductions in general PO and/or high-dose PO
      dispensing were observed following key interventions (e.g., Oxycodone delisting,
      prescription monitoring program [PMP] introduction in Ontario/British Columbia).
      While physician education intervention studied indicated mixed outcomes, media
      reporting was found to be associated with PO prescribing patterns. LIMITATIONS:
      The present review did not utilize systematic review standards or meta-analytic
      techniques given the large heterogeneity of data and outcomes reviewed.
      CONCLUSIONS: Recently emerging data help to better characterize PO-related use,
      harm and intervention indicators in Canada's general context of comparatively
      high-level PO dispensing and harms, yet major gaps in monitoring and information
      persist; this continues to be a problematic challenge, especially given the
      implementation of key PO-related interventions post-2010, the impact of which
      needs to be properly measured and understood.

PMID- 26218952
TI  - Tanshinone IIA Attenuates Chronic Pancreatitis-Induced Pain in Rats via
      Downregulation of HMGB1 and TRL4 Expression in the Spinal Cord.
AB  - BACKGROUND: Chronic pancreatitis (CP) is a long-standing inflammation of the
      exocrine pancreas, which typically results in severe and constant abdominal pain.
      Previous studies on the mechanisms underlying CP-induced pain have primarily
      focused on the peripheral nociceptive system. A role for a central mechanism in
      the mediation or modulation of abdominal pain is largely unknown. Tanshinone IIA
      (TSN IIA), an active component of the traditional Chinese medicine Danshen,
      exhibits anti-inflammatory properties via downregulation of the expression of
      high-mobility group protein B1 (HMGB1), a late proinflammatory cytokine. HMGB1
      binds and activates toll-like receptor 4 (TLR4) to induce spinal astrocyte
      activation and proinflammatory cytokine release in neuropathic pain. OBJECTIVE:
      In this study, we investigated the effect of TSN IIA on pain responses in rats
      with trinitrobenzene sulfonic acid (TNBS)-induced CP. The roles of central
      mechanisms in the mediation or modulation of CP were also investigated. STUDY
      DESIGN: A randomized, double-blind, placebo-controlled animal trial. METHODS: CP
      was induced in rats by intrapancreatic infusion of trinitrobenzene sulfonic acid
      (TNBS). Pancreatic histopathological changes were characterized with semi
      quantitative scores. The abdomen nociceptive behaviors were assessed with von
      Frey filaments. The effects of intraperitoneally administered TSN IIA on CP
      induced mechanical allodynia were tested. The spinal protein expression of HMGB1
      was determined by western blot. The spinal mRNA and protein expression of
      proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 were determined by RT-PCR
      and western blot, respectively. The spinal expression of the HMGB1 receptor TRL4
      and the astrocyte activation marker glial fibrillary acidic protein (GFAP) were
      determined by western blot or immunohistological staining after intraperitoneal
      injection of TSN IIA or intrathecal administration of a neutralizing anti-HMGB1
      antibody. RESULTS: TNBS infusion resulted in pancreatic histopathological changes
      of chronic pancreatitis and mechanical allodynia in rats. TSN IIA significantly
      attenuated TNBS-induced mechanical allodynia in a dose-dependent manner. TNBS
      significantly increased the spinal expression of HMGB1 and proinflammatory
      cytokines IL-1beta, TNF-alpha, and IL-6. These TNBS-induced changes were
      significantly inhibited by TSN IIA in a dose-dependent manner. Furthermore, TSN
      IIA, but not the neutralizing anti-HMGB1 antibody, significantly inhibited TNBS
      induced spinal TLR4 and GFAP expression. LIMITATIONS: In addition to TLR4, HMGB1
      can also bind to toll-like receptor-2 (TLR2) and the receptor for advanced
      glycation end products (RAGE). Additional studies are warranted to ascertain
      whether HMGB1 contributes to CP-induced pain through activation of these
      receptors. CONCLUSIONS: Our results suggest that spinal HMGB1 contributes to the
      development of CP-induced pain and can potentially be a therapeutic target. TSN
      IIA attenuates CP-induced pain via downregulation of spinal HMGB1 and TRL4
      expression. Therefore, TSN IIA may be a potential anti-nociceptive drug for the
      treatment of CP-induced pain.

PMID- 26218953
TI  - Clostridium Sacroiliitis (Gas Gangrene) Following Sacroiliac Joint Injection-
      Case Report and Review of the Literature.
AB  - An 80-year-old woman presented with chronic lumbosacral pain since her
      laminectomy and instrumentation 10 years ago. Examination was consistent with
      left sacroiliitis, and the patient underwent an elective left sacroiliac joint
      injection. Two days following her procedure she fell and landed on her left hip
      and on the next day, she presented to the emergency room with acutely worsening
      left gluteal pain. On evaluation in the emergency department, she was found to be
      suffering from a fever, headache, nausea, vomiting, and dysuria. A computed
      tomography (CT) scan was performed and this showed extensive foci of gas
      throughout the posterior aspect of the left iliopsoas muscle, sacrum, and ileum
      surrounding the left sacroiliac joint. The patient underwent emergent surgical
      debridement. The microbiology report of blood culture revealed clostridium
      perfringens, while her pathology showed necrosis and acute inflammation of
      fibroadipose tissue, skeletal muscle, and fat. The patient's hospital course
      resulted in multi-organ failure and the family elected for comfort care measures
      only. Unfortunately, she passed away 36 hours later. Septic arthritis is a
      potential catastrophic complication following intra-articular steroid therapy.
      The cause of the septic joint can be multifactorial but is likely caused by one
      of the following processes: direct inoculation of bacteria by the injection,
      hematogenous seeding of the percutaneous injection tract, or due to activation of
      a quiescent infection by the injected steroid. Clostridial spores are very
      resistant to standard aseptic skin preparations, including chlorhexidine and
      betadine solutions. The only effective methods to eliminate the spores is to heat
      them at a temperature greater than 100 degrees Celsius for 10 minutes or with use
      of a 10% potassium hydroxide (KOH) solution. We hypothesize that clostridium
      spores were present on the patient's skin from previous stool soiling, and that
      these were introduced directly into the soft tissue by needle trauma. Rare
      complications such as this one are scarcely reported in the literature and thus
      it becomes difficult to adequately identify risk factors or to formulate
      strategies to improve practice management.

PMID- 26218954
TI  - Intrathecal Baclofen in Spinal Spasticity: Frequency and Severity of Withdrawal
      Syndrome.
AB  - BACKGROUND: Intrathecal baclofen (ITB) delivered by programmable pump devices
      represents an important modality for long-term treatment of severe spinal
      spasticity. OBJECTIVE: One of the serious adverse events is a withdrawal syndrome
      after sudden interruption of ITB delivery. In this study, we analyzed the
      frequency and severity of this complication. Treatment recommendations follow.
      STUDY DESIGN: Case study. SETTING: Academic medical center. METHODS: A total of
      54 ITB pumps were successfully implanted in 39 patients with severe intractable
      spasticity (24 with spinal cord injury, 15 with multiple sclerosis, 24 men, age
      range 21-59 years). RESULTS: Eight patients developed a withdrawal syndrome on
      total a daily dose of ITB between 90-420 MUg/day. Seven patients had catheter
      related complications. In one patient, pump failure was observed due to its
      corrosion. Within the group, baclofen withdrawal syndrome occurred once in 20.1
      pump-years counted out of 160.4 pump-years of ITB treatment. LIMITATIONS: Small
      sample size. CONCLUSIONS: ITB withdrawal syndrome is a rare but life-threatening
      event and prompt diagnosis before treatment initiation is critical. The reported
      events were mostly mild due to the acute treatment regime and probably due to a
      lower dose of ITB. A prerequisite for successful ITB treatment is a deep
      knowledge of complications and their prompt management in the hands of a
      multidisciplinary team in specialized centers.

PMID- 26218955
TI  - The Use of Spinal Cord Neuromodulation in the Management of HIV-Related
      Polyneuropathy.
AB  - BACKGROUND: The prevalence of HIV-related neuropathy may rise nationwide as
      Highly Active Antiretroviral Therapy (HAART) usage and HIV-survival rates
      increase, resulting in higher referral rates to pain practitioners for analgesic
      strategies. However, if patients' symptoms are refractory to conservative
      measures, an advanced interventional approach may be indicated. OBJECTIVE: We
      present 2 cases of successful use of spinal cord neuromodulation in the treatment
      of HIV-related neuropathy. STUDY DESIGN: Case Report. METHODS: One patient
      experienced severe lower extremity burning pain, progressively worsening over the
      past 6 years. He had trouble ambulating, and pain was refractory to conservative
      treatments. The other patient suffered from low back pain and distal symmetrical
      polyneuropathy. A remote lumbar discectomy prior to his development of HIV
      disease resulted in marked improvement in lumbar spinal pain, but subsequent
      later development of neuropathic pain remained refractory to different treatment
      modalities. RESULTS: Both patients reported more than 90% improvement in pain
      during the spinal cord stimulator (SCS) trial, which led to permanent SCS
      implantation with equivalent success rates. One of them was followed up for 3
      years, and another one for 14 months before he moved overseas. Both of them
      reported an improved quality of life, reductions in the use of oral opioid
      analgesics, and increased ability to participate in daily activities without
      limitations. Neither patient sustained any infectious complications, lead
      migration, or required battery changes. LIMITATIONS: Controlled double blinded
      studies with a higher number of patients are needed to prove efficacy in these
      patients. CONCLUSION: These 2 cases demonstrate that SCS neuromodulation is a
      safe, viable, and efficacious option for patients whose HIV-related neuropathic
      type pain is refractory to conventional treatment modalities. Our patients appear
      to be the first case reports that show a remarkable efficacy of SCS in the
      management of HIV-related polyneuropathy.

PMID- 26218956
TI  - Peripheral and Neuraxial Chemical Neurolysis for the Management of Intractable
      Lower Extremity Pain in a Patient with Terminal Cancer.
AB  - We present the case of a 74-year-old man with Stage IV metastatic, multifocal,
      malignant fibrous histiocytoma (T2b, N1, M1, G4) invading the proximal area of
      the left lower extremity and resulting in intractable neuropathic pain along the
      distribution of the femoral nerve. He described the pain as being so severe to
      cause inability to ambulate without assistance or to sleep in a supine or prone
      position. After a spinal cord stimulation trial and a trial of intrathecal (IT)
      hydromorphone, both performed at an outside institution, had failed to achieve
      adequate pain relief, we decided to perform a femoral nerve chemical neurolysis
      with phenol under ultrasound (US) guidance. The intervention provided 6 months of
      almost complete pain relief. With the tumor spreading in girth distally and
      proximally to the scrotal and pelvic areas as well as to the lungs, and pain
      returning back to baseline, we proceeded with a second femoral nerve chemical
      neurolysis. Unfortunately we were not able to achieve adequate pain relief.
      Therefore we opted to proceed with a diagnostic injection of local anesthetic
      under fluoroscopic guidance at the left L2, L3, and L4 nerve roots level. This
      intervention provided 100% pain relief and was followed, a few days later, by
      chemical neurolysis with phenol 3%. The patient reported complete pain relief
      with the procedure and no sensory-motor related side effects or complications. He
      was able to enjoy the last 6 weeks of life with his wife and family, pain-free.
      With this report we add to the limited literature available regarding the
      management of intractable cancer pain with chemical neurolysis in and around the
      epidural space.

PMID- 26218957
TI  - Ischial Pain and Sitting Disability Due to Ischiogluteal Bursitis: Visual
      Vignette.
AB  - Ischial bursitis or ischiogluteal bursitis is the inflammation of the
      ischiogluteal bursa due to excessive or inappropriate physical exercise,
      prolonged sitting, running, repetitive jumping, and kicking. Since ischial
      bursitis is a rare, infrequently recognized pathology and is difficult to
      differentiate from the soft tissue disease and tumors (both malignant and
      benign), herein exemplified is a case with ischiogluteal bursitis whereby the
      role of magnetic resonance imaging (MRI) in the prompt diagnosis has been
      highlighted. 

PMID- 26218958
TI  - Recent Developments in Prescription Opioid-related Dispensing and Harm Indicators
      in Ontario, Canada.

PMID- 26218959
TI  - Adding Particulate or Non-Particulate Steroids to the Local Anesthetics When
      Performing Parasagittal Interlaminar Epidural Injections.

PMID- 26218960
TI  - Response: Authors' Reply to Adding Particulate or Non-Particulate Steroids to the
      Local Anesthetics When Performing Parasagittal Interlaminar Epidural Injections.

PMID- 26218961
TI  - Response to Knezevic et al: Reply from Manchikanti.

PMID- 26218962
TI  - Comment on: "Ulnar Tunnel Syndrome with Ultrasonographic Nerve Imaging".

PMID- 26218963
TI  - In Response to Coraci et al.

PMID- 26218964
TI  - Epidural Ahesiolysis Provides Misinformation.

PMID- 26218965
TI  - Chocolate and other cocoa products: effects on human reproduction and pregnancy.
AB  - Chocolate and other cocoa products are not all alike. They differ between
      themselves in term of nutrients, calories, and bioactive constituents. Therefore,
      some of them are unhealthy foods, whereas others do not affect health and still
      others are healthy foods. One wonders which chocolate and other cocoa derivatives
      can be considered as biofunctional food products. This review explores the
      constituents of cocoa and chocolate and summarizes evidence about the role of
      cocoa and chocolate components on human health and particularly on reproduction.
      On the basis of the literature review, it can be asserted that some kinds of
      cocoa products have favorable effects on human health at different stages of
      life. Women seem to be particularly favored by consuming of cocoa products, and
      chocolate with specific features can also be a good supplementary source of
      energy for pregnant woman. However, many aspects remain to be investigated and
      others are still to be clarified. Future studies and systematic reviews will shed
      light on some preventive effects and health benefits of cocoa products. 

PMID- 26218968
TI  - Robotic infrarenal paraaortic and pelvic nodal staging for endometrial cancer:
      feasibility and lymphatic complications.
AB  - INTRODUCTION: This study was designed to evaluate the feasibility and lymphatic
      complications of robotic pelvic and infrarenal paraaortic lymphadenectomy in
      endometrial cancer patients. MATERIAL AND METHODS: All patients diagnosed with
      high risk endometrial cancer during the study period were identified (n = 212).
      Clinical prospective data, with reassessment of lymphatic complications, was
      analysed for all cases (n = 140) planned for a complete robotic nodal staging.
      The outcome measures were: success rate of infrarenal paraaortic lymphadenectomy,
      the rate of lymphatic complications and factors associated with nodal yield.
      RESULTS: Of the 212 women, an open or restricted robotic procedure was performed
      in 57 women (27%) and no operation in 15 (7%), the latter due to disseminated
      disease or comorbidity. In 140 women (66%) in whom staging was intended, the
      lymphadenectomy included the infrarenal area in 70%, was restricted to the
      inframesenteric area in 21% and aborted or incomplete in 9%. The median number of
      paraaortic nodes was 10 (range 2-39). An unsuccessful staging was associated with
      high BMI and the surgeon's inexperience. At 1 year, three patients (2%) had
      developed a grade two lower limb lymphedema. Eleven women (8%) demonstrated
      pelvic lymphocysts; seven (64%) resolved spontaneously. Only one paraaortic
      lymphocyst was found; this required drainage. No cases of chylous ascites
      occurred. CONCLUSIONS: An infrarenal robotic paraaortic lymphadenectomy is
      feasible in 70% of high risk endometrial cancer cases when intended (88% in non
      obese patients operated by experienced surgeons), but is restricted in obese
      patients and by surgeon's inexperience.

PMID- 26218967
TI  - Acute health problems due to recreational drug use in patients presenting to an
      urban emergency department in Switzerland.
AB  - QUESTIONS UNDER STUDY: To describe acute toxicity of recreational drugs including
      novel psychoactive substances. METHODS: We included all cases presenting at the
      emergency department (ED) of the University Hospital of Basel, Switzerland,
      between October 2013 and September 2014 with acute toxicity due to self-reported
      recreational drug use or with symptoms/signs consistent with acute toxicity.
      Isolated ethanol intoxications were excluded. Intoxications were confirmed with
      immunoassays and liquid chromatography coupled with mass spectrometry (LC-MS/MS),
      which also detected novel psychoactive substances. RESULTS: Among the 47,767
      attendances at the ED, 216 were directly related to acute toxicity of
      recreational drugs. The mean patient age was 31 years and 69% were male.
      Analytical drug confirmation was available in 180 cases. Most presentations were
      related to cocaine (36%), cannabis (31%), opioids (13%), 3,4-methylenedioxy
      methamphetamine (MDMA, 9%), other amphetamines (7%), benzodiazepines (7%), and
      lysergic acid diethylamide (LSD, 5%). The substances most commonly detected
      analytically were cannabis (37%), cocaine (33%), opioids (29%), benzodiazepines
      (21%), and amphetamines including MDMA (13%). Notably, there were only two cases
      of novel psychoactive substances (2,5-dimethoxy-4-bromophenethylamine [2C-B] and
      pentylone). The most frequent symptoms were tachycardia (31%), anxiety (27%),
      nausea or vomiting (23%), and agitation (22%). Severe complications included
      myocardial infarction (2), psychosis (10), seizures (10), and 1 fatality. Most
      patients were discharged home (68%), 8% were admitted to intensive care and 9%
      were referred to psychiatric care. CONCLUSION: Medical problems related to
      illicit drugs mostly concerned cocaine and cannabis and mainly involved
      sympathomimetic toxicity and/or psychiatric disorders. ED presentations
      associated with novel psychoactive substances appeared to be relatively rare.

PMID- 26218969
TI  - Autologous stem cell transplantation in immunoglobulin light chain amyloidosis
      with factor X deficiency.
AB  - Acquired factor X deficiency and associated haemorrhage can be consequences of
      immunoglobulin light chain amyloidosis. There are limited data on the safety and
      efficacy of autologous stem cell transplant (ASCT) on factor X deficiency. We
      retrospectively reviewed immunoglobulin light chain amyloidosis patients with
      factor X levels below 50%, not on chronic anticoagulation who underwent ASCT at
      the Mayo Clinic, Rochester, Minnesota, USA, between April 1995 and December 2011.
      Twenty-seven of 358 patients (7.5%) met study criteria. Median pre-ASCT factor X
      was 36% (range: 2-49%). The most frequent and severe bleeding complications
      occurred in patients with factor X levels below 10%. Peri-procedural prophylaxis
      included activated recombinant factor VII, fresh frozen plasma and platelet
      transfusions. Steady-state post-ASCT factor X levels were determined in 12
      patients. Post-ASCT factor X levels increased in 100% of patients, with median
      factor X improvement of +32% (range: +8 to +92%). About 46.2% of patients were no
      longer factor X deficient after ASCT. The degree of improvement in factor X
      levels was correlated with an improvement in markers of renal involvement by
      amyloid. Improvement in factor X correlated with an improvement in the degree of
      total serum protein (rho = 0.54; P = 0.04) and proteinuria (rho = -0.54; P =
      0.04). Our findings support the decision to offer ASCT to factor X-deficient
      patients as both appropriate and efficacious.

PMID- 26218970
TI  - A comparison between MRI, sonography and Functional Independence Score in
      Haemophilia methods in diagnosis, evaluation and classification of arthropathy in
      severe haemophilia A and B.
AB  - Evaluation of joints in children with haemophilia is important in detecting
      abnormalities, staging their severity and following the effects of treatment. The
      aim of this study is to evaluate the correlation of FISH score (Functional
      Independence Score in Haemophilia) with the scores obtained by MRI and sonography
      for the diagnosis, evaluation and classification of arthropathy in severe
      haemophilia. In this cross-sectional study on 25 severe haemophilia patients,
      FISH, MRI and sonography procedures were performed in the elbow or knee joint.
      All patients' information, including age, type of haemophilia, affected joint,
      scores of MRI, sonography and FISH, dose of factor consumed, weight and
      prophylaxis protocol were collected and analysed. Among the 25 patients (age
      range of 11-70 years), 22 patients were haemophilia A and three patients were
      haemophilia B. Affected joints were right knee in 12 patients, left knee in nine
      and right elbow in four. There was only a statistically significant negative
      correlation between FISH and MRI Additive (A) scale (rs = -0.537, P = 0.006).
      Considering cartilage loss domain (related MRI A scale: 13-20), 20 patients (80%)
      were classified in this group with FISH scores ranged from 17 to 22. On the basis
      of our results, FISH scores in severe haemophilia patients were negatively
      correlated with MRI A scale. Also, it seems that a FISH score less than 22 could
      be considered as loss of cartilage; however, due to the small number of our
      patients, it needs further assessment in different populations. 

PMID- 26218971
TI  - Clinical characteristics of in-situ pulmonary artery thrombosis in Korea.
AB  - Little is known regarding the clinical features and course of in-situ pulmonary
      artery thrombosis (PAT). The aim of the present study was to investigate the
      clinical characteristics of PAT. Patients with PAT were retrospectively
      identified from a tertiary referral center in South Korea. A control group
      consisted of patients with pulmonary embolism in whom the right or left pulmonary
      artery was the largest pulmonary embolism-involved site. We compared various
      clinical parameters between the two groups. Of the 23 PAT patients, the most
      common underlying condition was tuberculosis-destroyed lung [11 (47.8%)],
      followed by pulmonary artery stump after lobectomy or pneumonectomy [7 (30.4%)].
      In all patients except one, PAT was located in the right or left pulmonary
      artery. Computed tomography scans demonstrated that clots were completely or
      partially resolved less frequently in the PAT group than in the control group [4
      (25%) versus 62 (90%); P < 0.001]. In the PAT group, three of the seven patients
      (43%) who had undergone anticoagulation therapy exhibited improvement, and one of
      the nine patients (11%) who had not received anticoagulation therapy experienced
      improvement; however, the difference was not significant. Tuberculosis-destroyed
      lung was the most common underlying condition in Korean PAT patients, followed by
      pulmonary artery stump after lung resection. The clots in patients with PAT were
      mostly located in the right or left pulmonary artery, and clot resolution was
      less frequent in the PAT group compared to the pulmonary embolism group. 

PMID- 26218972
TI  - Comparison of Subjective Refraction under Binocular and Monocular Conditions in
      Myopic Subjects.
AB  - To compare subjective refraction under binocular and monocular conditions, and to
      investigate the clinical factors affecting the difference in spherical refraction
      between the two conditions. We examined thirty eyes of 30 healthy subjects.
      Binocular and monocular refraction without cycloplegia was measured through
      circular polarizing lenses in both eyes, using the Landolt-C chart of the 3D
      visual function trainer-ORTe. Stepwise multiple regression analysis was used to
      assess the relations among several pairs of variables and the difference in
      spherical refraction in binocular and monocular conditions. Subjective spherical
      refraction in the monocular condition was significantly more myopic than that in
      the binocular condition (p < 0.001), whereas no significant differences were seen
      in subjective cylindrical refraction (p = 0.99). The explanatory variable
      relevant to the difference in spherical refraction between binocular and
      monocular conditions was the binocular spherical refraction (p = 0.032, partial
      regression coefficient B = 0.029) (adjusted R(2) = 0.230). No significant
      correlation was seen with other clinical factors. Subjective spherical refraction
      in the monocular condition was significantly more myopic than that in the
      binocular condition. Eyes with higher degrees of myopia are more predisposed to
      show the large difference in spherical refraction between these two conditions. 

PMID- 26218973
TI  - Possible Causal Link Between Idiopathic Intracranial Hypertension and the Misuse
      of Codeine-Based Products.

PMID- 26218981
TI  - Probabilistic characterisation of baseline noise in STR profiles.
AB  - There are three dominant contributing factors that distort short tandem repeat
      profile measurements, two of which, stutter and variations in the allelic peak
      heights, have been described extensively. Here we characterise the remaining
      component, baseline noise. A probabilistic characterisation of the non-allelic
      noise peaks is not only inherently useful for statistical inference but is also
      significant for establishing a detection threshold. We do this by analysing the
      data from 643 single person profiles for the Identifiler Plus kit and 303 for the
      PowerPlex 16 HS kit. This investigation reveals that although the dye colour is a
      significant factor, it is not sufficient to have a per-dye colour description of
      the noise. Furthermore, we show that at a per-locus basis, out of the Gaussian,
      log-normal, and gamma distribution classes, baseline noise is best described by
      log-normal distributions and provide a methodology for setting an analytical
      threshold based on that deduction. In the PowerPlex 16 HS kit, we observe
      evidence of significant stutter at two repeat units shorter than the allelic
      peak, which has implications for the definition of baseline noise and signal
      interpretation. In general, the DNA input mass has an influence on the noise
      distribution. Thus, it is advisable to study noise and, consequently, to infer
      quantities like the analytical threshold from data with a DNA input mass
      comparable to the DNA input mass of the samples to be analysed. 

PMID- 26218982
TI  - Complete mitochondrial genome database and standardized classification system for
      Canis lupus familiaris.
AB  - To contribute to the complete mitogenome database of the species Canis lupus
      familiaris and shed more light on its origin, we have sequenced mitochondrial
      genomes of 120 modern dogs from worldwide populations. Together with all the
      previously published mitogenome sequences of acceptable quality, we have
      reconstructed a global phylogenetic tree of 555 C. l. familiaris mitogenomes and
      standardized haplogroup nomenclature. The phylogenetic tree presented here and
      available online at http://clf.mtdna.tree.cm.umk.pl/ could be further used by
      forensic and evolutionary geneticists as well cynologists, for data quality
      control and unambiguous haplogroup classification. Our in-depth phylogeographic
      analysis of all C. l. familiaris mitogenomes confirmed that domestic dogs may
      have originated in East Asia during the Mesolithic and Upper Paleolithic time
      periods and started to expand to other parts of the world during Neolithic times.

PMID- 26218983
TI  - Phylogenetic analysis and forensic characteristics of 12 populations using 23 Y
      STR loci.
AB  - Genetic analysis of Y-STRs has the potential to be used to explore the complexity
      in population substructures and to perform forensic ancestry inference. In this
      study, 334 individuals from 12 populations were typed using the PowerPlex((r))
      Y23 System (Promega, USA) to investigate their relationship. Population
      comparisons with other East Asian populations collated from YHRD (Y-STR Haplotype
      Reference Database) were also performed. Variant alleles, including seven
      intermediate alleles in 15 samples were observed, while the novel allele 11.3 at
      the DYS549 locus was confirmed by sequencing. Our results showed that the
      fraction of unique haplotypes differed among the 12 populations studied here. A
      close relationship was found between Chinese and other East Asian populations.
      The present study contributed to the enrichment of the forensic Y-chromosome
      databases with a high resolution 23 Y-STR marker set, which is informative in
      forensic casework, such as familial searching and estimating the geographical
      origin of the offender. 

PMID- 26218984
TI  - The effects of paid maternity leave: Evidence from Temporary Disability
      Insurance.
AB  - This paper investigates the effects of a large-scale paid maternity leave program
      on birth outcomes in the United States. In 1978, states with Temporary Disability
      Insurance (TDI) programs were required to start providing wage replacement
      benefits to pregnant women, substantially increasing access to antenatal and
      postnatal paid leave for working mothers. Using natality data, I find that TDI
      paid maternity leave reduces the share of low birth weight births by 3.2 percent,
      and the estimated treatment-on-the-treated effect is over 10 percent. It also
      decreases the likelihood of early term birth by 6.6 percent. Paid maternity leave
      has particularly large impacts on the children of unmarried and black mothers. 

PMID- 26218985
TI  - Financial incentives for kidney donation: A comparative case study using
      synthetic controls.
AB  - Although many commentators called for increased efforts to incentivize organ
      donations, theorists and some evidence suggest these efforts will be ineffective.
      Studies examining the impact of tax incentives generally report zero/negative
      coefficients, but these studies incorrectly define their tax variables and rely
      on difference-in-differences despite likely failures of the parallel trends
      assumption. We identify the causal effect of tax legislation to serve as an organ
      donor on living kidney donation rates in the U.S. states using more precise tax
      data and allowing for heterogeneous time-variant causal effects. Employing a
      synthetic control method, we find that the passage of tax incentive legislation
      increased living unrelated kidney donation rates by 52 percent in New York
      relative to a comparable synthetic New York in the absence of legislation. It is
      possible that New York is unique, but our methodology does not allow us to
      measure accurately effects in other states. 

PMID- 26218987
TI  - Flux Balance Analysis with Objective Function Defined by Proteomics Data
      Metabolism of Mycobacterium tuberculosis Exposed to Mefloquine.
AB  - We present a study of the metabolism of the Mycobacterium tuberculosis after
      exposure to antibiotics using proteomics data and flux balance analysis (FBA).
      The use of FBA to study prokaryotic organisms is well-established and allows
      insights into the metabolic pathways chosen by the organisms under different
      environmental conditions. To apply FBA a specific objective function must be
      selected that represents the metabolic goal of the organism. FBA estimates the
      metabolism of the cell by linear programming constrained by the stoichiometry of
      the reactions in an in silico metabolic model of the organism. It is assumed that
      the metabolism of the organism works towards the specified objective function. A
      common objective is the maximization of biomass. However, this goal is not
      suitable for situations when the bacterium is exposed to antibiotics, as the goal
      of organisms in these cases is survival and not necessarily optimal growth. In
      this paper we propose a new approach for defining the FBA objective function in
      studies when the bacterium is under stress. The function is defined based on
      protein expression data. The proposed methodology is applied to the case when the
      bacterium is exposed to the drug mefloquine, but can be easily extended to other
      organisms, conditions or drugs. We compare our method with an alternative method
      that uses experimental data for adjusting flux constraints. We perform
      comparisons in terms of essential enzymes and agreement using enzyme abundances.
      Results indicate that using proteomics data to define FBA objective functions
      yields less essential reactions with zero flux and lower error rates in
      prediction accuracy. With flux variability analysis we observe that overall
      variability due to alternate optima is reduced with the incorporation of
      proteomics data. We believe that incorporating proteomics data in the objective
      function used in FBA may help obtain metabolic flux representations that better
      support experimentally observed features. 

PMID- 26218986
TI  - Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1
      and U2AF65.
AB  - Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin
      (HTT) gene. Recent evidence suggests that HD is a consequence of multimodal, non
      mutually exclusive mechanisms of pathogenesis that involve both HTT protein- and
      HTT RNA-triggered mechanisms. Here we provide further evidence for the role of
      expanded HTT (expHTT) RNA in HD by demonstrating that a fragment of expHTT is
      cytotoxic in the absence of any translation and that the extent of cytotoxicity
      is similar to the cytotoxicity of an expHTT protein fragment encoded by a
      transcript of similar length and with a similar repeat size. In addition, full
      length (FL) expHTT is retained in the nucleus. Overexpression of the splicing
      factor muscleblind-like 1 (MBNL1) increases nuclear retention of expHTT and
      decreases the expression of expHTT protein in the cytosol. The splicing and
      nuclear export factor U2AF65 has the opposite effect, decreasing expHTT nuclear
      retention and increasing expression of expHTT protein. This suggests that MBNL1
      and U2AF65 play a role in nuclear export of expHTT RNA. 

PMID- 26218988
TI  - Robust and Soft Elastomeric Electronics Tolerant to Our Daily Lives.
AB  - Clothes represent a unique textile, as they simultaneously provide robustness
      against our daily activities and comfort (i.e., softness). For electronic devices
      to be fully integrated into clothes, the devices themselves must be as robust and
      soft as the clothes themselves. However, to date, no electronic device has ever
      possessed these properties, because all contain components fabricated from
      brittle materials, such as metals. Here, we demonstrate robust and soft
      elastomeric devices where every component possesses elastomeric characteristics
      with two types of single-walled carbon nanotubes added to provide the necessary
      electronic properties. Our elastomeric field effect transistors could tolerate
      every punishment our clothes experience, such as being stretched (elasticity: ~
      110%), bent, compressed (>4.0 MPa, by a car and heels), impacted (>6.26 kg m/s,
      by a hammer), and laundered. Our electronic device provides a novel design
      principle for electronics and wide range applications even in research fields
      where devices cannot be used. 

PMID- 26218989
TI  - Multipotent bone marrow stromal cell therapy promotes endogenous cell
      proliferation following ischemic stroke.
AB  - Despite extensive research over the years, there still exists some debate as to
      what constitutes the optimal therapeutic strategy to promote recovery following
      stroke. Due to the complexity of injured brain pathophysiology, treatment
      approaches should ideally address numerous factors, ultimately aiming to promote
      tissue protection, axonal regrowth and functional recovery. This study extends
      the understanding of the effects of bone marrow stromal cell (BMSC) treatment
      following experimentally induced ischemic stroke in rats. Focal ischemic brain
      injury was experimentally induced in rats by placing a preformed clot into the
      middle cerebral artery. Animals were injected intravenously with BMSCs at 24 h
      after stroke and were killed 7 days post injury. When administered BMSCs
      following stroke, the neurological outcome was significantly improved relative to
      controls. There was an increase in the number of BMSCs labelled with BrdU present
      in the injured hemisphere of the brain compared to the non-injured side.
      Furthermore, administration of BMSCs also led to increases in astrocytosis,
      vascularization and endogenous proliferation. These findings provide insight into
      the mechanisms of action of BMSC treatment and further argue for the therapeutic
      potential of BMSCs as an effective treatment following cerebral stroke. 

PMID- 26218990
TI  - Brachytherapy treatment planning commissioning: effect of the election of proper
      bibliography and finite size of TG-43 input data on standard treatments.
AB  - The aim of this work is to evaluate the performance of a commercial brachytherapy
      treatment planning system (TPS) with TG-43 Vendors Input Data (VID), analyze
      possible discrepancies with respect to a proper reference source and its
      implications for standard treatments, and judge the effectiveness of certain
      widespread recommended quality controls to find potential errors related with the
      interpolations of TG-43 VID tables. The TPS evaluated was a BrachyVision 8.6
      loaded with TG-43 VID for a VariSource high-dose-rate 192Ir source (Vs2000). The
      reference data chosen were the TG-43 data published in the literature. In the
      first step, we compared TG-43 VID with respect to the chosen reference data.
      Next, we used percent dose-rate differences in a point array matrix to compare
      the outcomes of the TPS on standard treatment setup with respect to an in-house
      developed program (MATLAB R2009a-based) loaded with the chosen full TG-43
      reference data. The cases with major discrepancies were evaluated using the gamma
      index analysis. The comparison with the reference data indicated a lack of sample
      in the angles between near to the tip (between 165 < theta < 180) and cable (0 <
      theta < 15) of the F(r,theta)(VID), which causes a dose underestimation of
      approximately 17% in the investigated points due to inaccurate interpolations.
      The differences over 2% encompassed approximately 17% of the surrounding source
      volume. These results have special relevance in treatment using one applicator
      with a few dwell steps or in Fletcher treatments where 10% dose underestimates
      were identified within the tumor or in organs at risk, respectively. Our results
      suggest that the differences found in the TPS under study are created by a lack
      of information on the angles in high-gradient zones in the F(r,theta)(VID), which
      generates important differences in dosimetric results. In contrast, the gamma
      analysis shows very good results (between 90% and 100% of passed points) in the
      analyzed treatments (one dwell and Fletcher). Further studies are required to
      exclude the possibility of finding noticeable effects in the DVH of treatment
      plans caused by the discrepancies here described. To achieve more strict control
      over the TPS dose-rate calculation, we recommend using QA test thinking in a
      source with nonaxial symmetry, adding a control point on the angles of the high
      dose gradient zones (e.g., between 0 degrees  and 15 degrees  and between 165
      degrees  and 180 degrees ). More studies are required to achieve full
      understanding of the clinical implication of such discrepancies.

PMID- 26218991
TI  - A phantom study investigating the relationship between ground-glass opacity
      visibility and physical detectability index in low-dose chest computed
      tomography.
AB  - In this study, the relationship between ground-glass opacity (GGO) visibility and
      physical detectability index in low-dose computed tomography (LDCT) for lung
      cancer screening was investigated. An anthropomorphic chest phantom that included
      synthetic GGOs with CT numbers of -630 Hounsfield units (HU; high attenuation
      GGO: HGGO) and -800 HU (low attenuation GGO: LGGO), and three phantoms for
      physical measurements were employed. The phantoms were scanned using 12 CT
      systems located in 11 screening centers in Japan. The slice thicknesses and CT
      dose indices (CTDI(vol)) varied over 1.0-5.0 mm and 0.85-3.30 mGy, respectively,
      and several reconstruction kernels were used. Physical detectability index values
      were calculated from measurements of resolution, noise, and slice thickness
      properties for all image sets. Five radiologists and one thoracic surgeon, blind
      to one another's observations, evaluated GGO visibility using a five-point
      scoring system. The physical detectability index correlated reasonably well with
      the GGO visibility (R2 = 0.709, p < 0.01 for 6 mm HGGO and R2 = 0.646, p < 0.01
      for 10 mm LGGO), and was nearly proportional to the CTDI(vol). Consequently, the
      CTDI(vol) also correlated reasonably well with the GGO visibility (R2 = 0.701, p
      < 0.01 for 6 mm HGGO and R2 = 0.680, p < 0.01 for 10 mm LGGO). As a result, the
      CTDI(vol) was nearly dominant in the GGO visibility for image sets with different
      reconstruction kernels and slice thicknesses, used in this study.

PMID- 26218992
TI  - Long-term evaluation and cross-checking of two geometric calibrations of kV and
      MV imaging systems for Linacs.
AB  - Geometric or mechanical accuracy of kV and MV imaging systems of two Varian
      TrueBeam linacs have been monitored by two geomertirc calibration systems, Varian
      IsoCal geometric calibration system and home-developed gQA system. Results of
      both systems are cross-checked and the long-term geometric stabilities of linacs
      are evaluated. Two geometric calibration methodologies have been used to assess
      kV and MV imaging systems and their coincidence periodically on two TrueBeam
      linacs for about one year. Both systems analyze kV or MV projection images of
      special designed phantoms to retrieve geometric parameters of the imaging
      systems. The isocenters - laser isocenter and centers of rotations of kV imager
      and EPID - are then calculated, based on results of multiple projections from
      different angles. Long-term calibration results from both systems are compared
      for cross-checking. There are 24 sessions of side-by-side calibrations performed
      by both systems on two TrueBeam linacs. All the disagreements of isocenters
      between two calibrations systems are less than 1 mm with +/- 0.1 mm SD. Most of
      the large disagreements occurred in vertical direction (AP direction), with an
      averaged disagreement of 0.45 mm. The average disagreements of isocenters are
      0.09 mm in other directions. Additional to long-term calibration monitoring, for
      the accuracy test, special tests were performed by misaligning QA phantoms on
      purpose (5 mm away from setup isocenter in AP, SI, and lateral directions) to
      test the liability performance of both systems with the known deviations. The
      errors are within 0.5 mm. Both geometric calibration systems, IsoCal and gQA, are
      capable of detecting geometric deviations of kV and MV imaging systems of linacs.
      The long-term evaluation also shows that the deviations of geometric parameters
      and the geometric accuracies of both linacs are small and very consistent during
      the one-year study period.

PMID- 26218993
TI  - Evaluation of GMI and PMI diffeomorphic-based demons algorithms for aligning PET
      and CT Images.
AB  - Fusion of anatomic information in computed tomography (CT) and functional
      information in 18F-FDG positron emission tomography (PET) is crucial for accurate
      differentiation of tumor from benign masses, designing radiotherapy treatment
      plan and staging of cancer. Although current PET and CT images can be acquired
      from combined 18F-FDG PET/CT scanner, the two acquisitions are scanned separately
      and take a long time, which may induce potential positional errors in global and
      local caused by respiratory motion or organ peristalsis. So registration
      (alignment) of whole-body PET and CT images is a prerequisite for their
      meaningful fusion. The purpose of this study was to assess the performance of two
      multimodal registration algorithms for aligning PET and CT images. The proposed
      gradient of mutual information (GMI)-based demons algorithm, which incorporated
      the GMI between two images as an external force to facilitate the alignment, was
      compared with the point-wise mutual information (PMI) diffeomorphic-based demons
      algorithm whose external force was modified by replacing the image intensity
      difference in diffeomorphic demons algorithm with the PMI to make it appropriate
      for multimodal image registration. Eight patients with esophageal cancer(s) were
      enrolled in this IRB-approved study. Whole-body PET and CT images were acquired
      from a combined 18F-FDG PET/CT scanner for each patient. The modified Hausdorff
      distance (d(MH)) was used to evaluate the registration accuracy of the two
      algorithms. Of all patients, the mean values and standard deviations (SDs) of
      d(MH) were 6.65 (+/- 1.90) voxels and 6.01 (+/- 1.90) after the GMI-based demons
      and the PMI diffeomorphic-based demons registration algorithms respectively.
      Preliminary results on oncological patients showed that the respiratory motion
      and organ peristalsis in PET/CT esophageal images could not be neglected,
      although a combined 18F-FDG PET/CT scanner was used for image acquisition. The
      PMI diffeomorphic-based demons algorithm was more accurate than the GMI-based
      demons algorithm in registering PET/CT esophageal images.

PMID- 26218994
TI  - Single-isocenter hybrid IMRT plans versus two-isocenter conventional plans and
      impact of intrafraction motion for the treatment of breast cancer with
      supraclavicular lymph nodes involvement.
AB  - The purpose of this study was to compare the single-isocenter, four-field hybrid
      IMRT with the two-isocenter techniques to treat the whole breast and
      supraclavicular fields and to investigate the intrafraction motions in both
      techniques in the superior direction. Fifteen breast cancer patients who
      underwent lumpectomy and adjuvant radiation to the whole breast and
      supraclavicular (SCV) fossa at our institution were selected for this study. Two
      planning techniques were compared for the treatment of the breast and SCV lymph
      nodes. The patients were divided into three subgroups according to the whole
      breast volume. For the two-isocenter technique, conventional wedged or field
      within-a-field tangents (FIF) were used to match with the same anterior field for
      the SCV region. For the single-isocenter technique, four-field hybrid IMRT was
      used for the tangent fields matched with a half blocked anterior field for the
      SCV region. To simulate the intrafraction uncertainties in the longitudinal
      direction for both techniques, the treatment isocenters were shifted by 1 mm and
      2 mm in the superior direction. The average breast clinical tumor volume (CTV)
      receiving 100% (V(100%)) of the prescription dose (50 Gy) was 99.3% +/- 0.5% and
      96.4% +/- 1.2% for the for two-isocenter and single-isocenter plans (r < 0.05),
      respectively. The breast CTV receiving 95% of the prescription dose (V(95%)) was
      close to 100% in both techniques. The average breast CTV receiving 105% (V(105%))
      of the prescription dose was 32.4% +/- 19.3% and 23.8% +/- 13.3% (r = 0.08). The
      percentage volume of the breast CTV receiving 110% of the dose was 0.4% +/- 1.2%
      in the two-isocentric technique vs. 0.1% +/- 0.2% in the single-isocentric
      technique. The average uniformity index was 0.91 +/- 0.02 vs. 0.91 +/- 0.01 in
      both techniques (p = 0.04), but had no clinical impact. The percentage volume of
      the contralateral breast receiving a dose of 1 Gy was less than 2.3% in small
      breast patients and insignificant for medium and large breast sizes. The
      percentage of the total lung volume receiving > 20 Gy (V(20Gy)) and the heart
      receiving > 30 Gy (V(30Gy)) were 13.6% vs. 14.3% (r = 0.03) and 1.25% vs. 1.2% (r
      = 0.62), respectively. Shifting the treatment isocenter by 1 mm and 2 mm
      superiorly showed that the average maximum dose to 1 cc of the breast volume was
      55.5 +/- 1.8 Gy and 58.6 +/- 4.3 Gy in the two-isocentric technique vs. 56.4 +/-
      2.1 Gy and 59.1 +/- 5.1 Gy in the single-isocentric technique (r = 0.46, 0.87),
      respectively. The single-isocenter technique using four-field hybrid IMRT
      approach resulted in comparable plan quality as the two-isocentric technique. The
      single-isocenter technique is more sensitive to intra-fraction motion in the
      superior direction compared to the two-isocentric technique. The advantages of
      the single-isocenter include elimination of isocentric errors due to couch and
      collimator rotations and reduction in treatment time. This study supports
      consideration of a single-isocenter four-field hybrid IMRT technique for patients
      undergoing breast and supraclavicular nodal irradiation.

PMID- 26218995
TI  - Feasibility of using respiration-averaged MR images for attenuation correction of
      cardiac PET/MR imaging.
AB  - Cardiac imaging is a promising application for combined PET/MR imaging. However,
      current MR imaging protocols for whole-body attenuation correction can produce
      spatial mismatch between PET and MR-derived attenuation data owing to a disparity
      between the two modalities' imaging speeds. We assessed the feasibility of using
      a respiration-averaged MR (AMR) method for attenuation correction of cardiac PET
      data in PET/MR images. First, to demonstrate the feasibility of motion imaging
      with MR, we used a 3T MR system and a two-dimensional fast spoiled gradient
      recalled echo (SPGR) sequence to obtain AMR images ofa moving phantom. Then, we
      used the same sequence to obtain AMR images of a patient's thorax under free
      breathing conditions. MR images were converted into PET attenuation maps using a
      three-class tissue segmentation method with two sets of predetermined CT numbers,
      one calculated from the patient-specific (PS) CT images and the other from a
      reference group (RG) containing 54 patient CT datasets. The MR-derived
      attenuation images were then used for attenuation correction of the cardiac PET
      data, which were compared to the PET data corrected with average CT (ACT) images.
      In the myocardium, the voxel-by-voxel differences and the differences in mean
      slice activity between the AMR-corrected PET data and the ACT-corrected PET data
      were found to be small (less than 7%). The use of AMR-derived attenuation images
      in place of ACT images for attenuation correction did not affect the summed
      stress score. These results demonstrate the feasibility of using the proposed
      SPGR-based MR imaging protocol to obtain patient AMR images and using those
      images for cardiac PET attenuation correction. Additional studies with more
      clinical data are warranted to further evaluate the method.

PMID- 26218996
TI  - Effect of interfractional shoulder motion on low neck nodal targets for patients
      treated using volumetric-modulated arc therapy (VMAT).
AB  - VMAT is an important tool in the treatment of head and neck cancers, many of
      which also require treatment to the supraclavicular lymph nodes. However, full
      VMAT arcs treating this nodal region necessarily cause entrance beam to pass
      through patients' shoulders. Thus, interfractional variations in shoulder
      position may cause unwanted dose perturbations. To assess this possibility, six
      patients undergoing treatment at our institution for head and neck cancers with
      associated supraclavicular lymph node treatment were imaged with in-room CT-on
      rails during the course of their treatments. This allowed for the establishment
      of a true record of the actual shoulder position during selected treatment
      fractions. Then, a full VMAT plan and a plan with VMAT arcs superior to the
      shoulder and a static anteroposterior field inferiorly were copied onto the
      patients' weekly image sets. The average one-dimensional shoulder motion was
      generally within 10 mm of the simulated position, with some notable exceptions.
      The standard deviation in week-to-week shoulder position relative to simulation
      was 4.3 mm and 4.2 mm in the SI and AP dimensions, respectively. The average
      nodal target mean dose across all fractions sampled was within 5% of planned for
      all patients and both plans. Similarly, the average D95 for the nodal target was
      within 5% of planned across all fractions sampled, with the single exception of
      the full VMAT plan for one patient. In most cases, the standard deviation in both
      target mean dose and D95 was smaller with the VMAT+static AP field plan than it
      was with the full VMAT plan.

PMID- 26218997
TI  - Dosimetric evaluation of the Acuros XB algorithm for a 4 MV photon beam in head
      and neck intensity-modulated radiation therapy.
AB  - In this study, we assessed the differences in the dose distribution of a 4 MV
      photon beam among different calculation algorithms: the Acuros XB (AXB)
      algorithm, the analytic anisotropic algorithm (AAA), and the pencil beam
      convolution (PBC) algorithm (ver. 11.0.31), in phantoms and in clinical intensity
      modulated radiation therapy (IMRT) plans. Homogeneous and heterogeneous,
      including middle-, low-, and high-density, phantoms were combined to assess the
      percentage depth dose and lateral dose profiles among AXB, AAA, and PBC. For the
      phantom containing the low-density area, AXB was in agreement with measurement
      within 0.5%, while the greatest differences between the AAA and PBC calculations
      and measurement were 2.7% and 3.6%, respectively. AXB showed agreement with
      measurement within 2.5% at the high-density area, while AAA and PBC overestimated
      the dose by more than 4.5% and 4.0%, respectively. Furthermore, 15 IMRT plans,
      calculated using AXB, for oropharyngeal, hypopharyngeal, and laryngeal carcinomas
      were analyzed. The dose prescription was 70 Gy to 50% of the planning target
      volume (PTV70). Subsequently, each plan was recalculated using AAA and PBC while
      maintaining the AXB-calculated monitor units, leaf motion, and beam arrangement.
      Additionally, nine hypopharyngeal and laryngeal cancer patients were analyzed in
      terms of PTV70 for cartilaginous structures (PTV(70_cartilage)). The doses
      covering 50% to PTV70 calculated by AAA and PBC were 2.1% +/- 1.0% and 3.7% +/-
      0.8% significantly higher than those using AXB, respectively (p < 0.01). The
      increases in doses to PTV(70_cartilage) calculated by AAA and PBC relative to AXB
      were 3.9% and 5.3% on average, respectively, and were relatively greater than
      those in the entire PTV70. AXB was found to be in better agreement with
      measurement in phantoms in heterogeneous areas for the 4 MV photon beam.
      Considering AXB as the standard, AAA and PBC overestimated the IMRT dose for head
      and neck cancer. The dosimetric differences should not be ignored, particularly
      with cartilaginous structures in PTV.

PMID- 26218998
TI  - Characteristics of a novel treatment system for linear accelerator-based
      stereotactic radiosurgery.
AB  - The purpose of this study is to characterize the dosimetric properties and
      accuracy of a novel treatment platform (Edge radiosurgery system) for localizing
      and treating patients with frameless, image-guided stereotactic radiosurgery
      (SRS) and stereotactic body radiotherapy (SBRT). Initial measurements of various
      components of the system, such as a comprehensive assessment of the dosimetric
      properties of the flattening filter-free (FFF) beams for both high definition
      (HD120) MLC and conical cone-based treatment, positioning accuracy and beam
      attenuation of a six degree of freedom (6DoF) couch, treatment head leakage test,
      and integrated end-to-end accuracy tests, have been performed. The end-to-end
      test of the system was performed by CT imaging a phantom and registering hidden
      targets on the treatment couch to determine the localization accuracy of the
      optical surface monitoring system (OSMS), cone-beam CT (CBCT), and MV imaging
      systems, as well as the radiation isocenter targeting accuracy. The deviations
      between the percent depth-dose curves acquired on the new linac-based system
      (Edge), and the previously published machine with FFF beams (TrueBeam) beyond
      D(max) were within 1.0% for both energies. The maximum deviation of output
      factors between the Edge and TrueBeam was 1.6%. The optimized dosimetric leaf gap
      values, which were fitted using Eclipse dose calculations and measurements based
      on representative spine radiosurgery plans, were 0.700 mm and 1.000 mm,
      respectively. For the conical cones, 6X FFF has sharper penumbra ranging from 1.2
      1.8 mm (80%-20%) and 1.9-3.8 mm (90%-10%) relative to 10X FFF, which has 1.2
      2.2mm and 2.3-5.1mm, respectively. The relative attenuation measurements of the
      couch for PA, PA (rails-in), oblique, oblique (rails-out), oblique (rails-in)
      were: -2.0%, -2.5%, -15.6%, -2.5%, -5.0% for 6X FFF and -1.4%, -1.5%, -12.2%, 
      2.5%, -5.0% for 10X FFF, respectively, with a slight decrease in attenuation
      versus field size. The systematic deviation between the OSMS and CBCT was -0.4 +/
      0.2 mm, 0.1+/- 0.3mm, and 0.0 +/- 0.1 mm in the vertical, longitudinal, and
      lateral directions. The mean values and standard deviations of the average
      deviation and maximum deviation of the daily Winston-Lutz tests over three months
      are 0.20 +/- 0.03 mm and 0.66 +/- 0.18 mm, respectively. Initial testing of this
      novel system demonstrates the technology to be highly accurate and suitable for
      frameless, linac-based SRS and SBRT treatment.

PMID- 26218999
TI  - Determining the optimal dosimetric leaf gap setting for rounded leaf-end
      multileaf collimator systems by simple test fields.
AB  - Individual QA for IMRT/VMAT plans is required by protocols. Sometimes plans
      cannot pass the institute's QA criteria. For the Eclipse treatment planning
      system (TPS) with rounded leaf-end multileaf collimator (MLC), one practical way
      to improve the agreement of planned and delivered doses is to tune the value of
      dosimetric leaf gap (DLG) in the TPS from the measured DLG. We propose that this
      step may be necessary due to the complexity of the MLC system, including
      dosimetry of small fields and the tongue-and-groove (T&G) effects, and report our
      use of test fields to obtain linac-specific optimal DLGs in TPSs. More than 20
      original patient plans were reoptimized with the linac-specific optimal DLG
      value. We examined the distribution of gaps and T&G extensions in typical patient
      plans and the effect of using the optimal DLG on the distribution. The QA pass
      rate of patient plans using the optimal DLG was investigated. The dose-volume
      histograms (DVHs) of targets and organs at risk were checked. We tested three MLC
      systems (Varian millennium 120 MLC, high-definition 120 MLC, and Siemens 160 MLC)
      installed in four Varian linear accelerators (linacs) (TrueBEAM STx, Trilogy,
      Clinac 2300 iX, and Clinac 21 EX) and 1 Siemens linac (Artiste). With an optimal
      DLG, the individual QA for all those patient plans passed the institute's
      criteria (95% in DTA test or gamma test with 3%/3 mm/10%), even though most of
      these plans had failed to pass QA when using original DLGs optimized from typical
      patient plans or from the optimization process (automodeler) of Pinnacle TPS.
      Using either our optimal DLG or one optimized from typical patient plans or from
      the Pinnacle optimization process yielded similar DVHs.

PMID- 26219000
TI  - Amplitude gating for a coached breathing approach in respiratory gated 10 MV
      flattening filter-free VMAT delivery.
AB  - The purpose of this study was to investigate amplitude gating combined with a
      coached breathing strategy for 10 MV flattening filter-free (FFF) volumetric
      modulated arc therapy (VMAT) on the Varian TrueBeam linac. Ten patient plans for
      VMAT SABR liver were created using the Eclipse treatment planning system (TPS).
      The verification plans were then transferred to a CT-scanned Quasar phantom and
      delivered on a TrueBeam linac using a 10 MV FFF beam and Varian's real-time
      position management (RPM) system for respiratory gating based on breathing
      amplitude. Breathing traces were acquired from ten patients using two kinds of
      breathing patterns: free breathing and an interrupted (~ 5 s pause) end of exhale
      coached breathing pattern. Ion chamber and Gafchromic film measurements were
      acquired for a gated delivery while the phantom moved under the described
      breathing patterns, as well as for a nongated stationary phantom delivery. The
      gate window was set to obtain a range of residual target motion from 2-5 mm. All
      gated deliveries on a moving phantom have been shown to be dosimetrically
      equivalent to the nongated deliveries on a static phantom, with differences in
      point dose measurements under 1% and average gamma 2%/2 mm agreement above 98.7%.
      Comparison with the treatment planning system also resulted in good agreement,
      with differences in point-dose measurements under 2.5% and average gamma 3%/3 mm
      agreement of 97%. The use of a coached breathing pattern significantly increases
      the duty cycle, compared with free breathing, and allows for shorter treatment
      times. Patients' free-breathing patterns contain considerable variability and,
      although dosimetric results for gated delivery may be acceptable, it is difficult
      to achieve efficient treatment delivery. A coached breathing pattern combined
      with a 5 mm amplitude gate, resulted in both high-quality dose distributions and
      overall shortest gated beam delivery times.

PMID- 26219001
TI  - Dosimetric effect due to the motion during deep inspiration breath hold for left
      sided breast cancer radiotherapy.
AB  - Deep inspiration breath-hold (DIBH) radiotherapy for left-sided breast cancer can
      reduce cardiac exposure and internal motion. We modified our in-house treatment
      planning system (TPS) to retrospectively analyze breath-hold motion log files to
      calculate the dosimetric effect of the motion during breath hold. Thirty left
      sided supine DIBH breast patients treated using AlignRT were studied. Breath-hold
      motion was recorded - three translational and three rotational displacements of
      the treatment surface - the Real Time Deltas (RTD). The corresponding delivered
      dose was estimated using the beam-on portions of the RTDs. Each motion was used
      to calculate dose, and the final estimated dose was the equally weighted average
      of the multiple resultant doses. Ten of thirty patients had internal mammary
      nodes (IMN) purposefully included in the tangential fields, and we evaluated the
      percentage of IMN covered by 40 Gy. The planned and delivered heart mean dose,
      lungs V20 (volume of the lungs receiving > 20 Gy), percentage of IMN covered by
      40 Gy, and IMN mean dose were compared. The averaged mean and standard deviation
      of the beam-on portions of the absolute RTDs were 0.81 +/- 1.29 mm, 0.68 +/-
      0.85mm, 0.76 +/- 0.85 mm, 0.96 degrees  +/- 0.49 degrees , 0.93 degrees  +/- 0.43
      degrees , and 1.03 degrees  +/- 0.50 degrees , for vertical, longitudinal,
      lateral, yaw, roll, and pitch, respectively. The averaged planned and delivered
      mean heart dose were 99 and 101 cGy. Lungs V20 were 6.59% and 6.74%. IMN 40 Gy
      coverage was 83% and 77%, and mean IMN dose was 4642 and 4518 cGy. The averaged
      mean motion during DIBH was smaller than 1 mm and 1 degrees , which reflects the
      relative reproducibility of the patient breath hold. On average, the mean heart
      dose and lungs V20 were reasonably close to what have been planned. IMN 40 Gy
      coverage might be modestly reduced for certain cases.

PMID- 26219002
TI  - Use of TrueBeam developer mode for imaging QA.
AB  - The purpose of this study was to automate regular Imaging QA procedures to become
      more efficient and accurate. Daily and monthly imaging QA for SRS and SBRT
      protocols were fully automated on a Varian linac. A three-step paradigm where the
      data are automatically acquired, processed, and analyzed was defined. XML scripts
      were written and used in developer mode in a TrueBeam linac to automatically
      acquire data. MATLAB R013B was used to develop an interface that could allow the
      data to be processed and analyzed. Hardware was developed that allowed the
      localization of several phantoms simultaneously on the couch. 14 KV CBCTs from
      the Emma phantom were obtained using a TrueBeam onboard imager as example of data
      acquisition and analysis. The images were acquired during two months. Artifacts
      were artificially introduced in the images during the reconstruction process
      using iTool reconstructor. Support vector machine algorithms to automatically
      identify each artifact were written using the Machine Learning MATLAB R2011
      Toolbox. A daily imaging QA test could be performed by an experienced medical
      physicist in 14.3 +/- 2.4 min. The same test, if automated using our paradigm,
      could be performed in 4.2 +/- 0.7 min. In the same manner, a monthly imaging QA
      could be performed by a physicist in 70.7 +/- 8.0 min and, if fully automated, in
      21.8 +/- 0.6 min. Additionally, quantitative data analysis could be automatically
      performed by Machine Learning Algorithms that could remove the subjectivity of
      data interpretation in the QA process. For instance, support vector machine
      algorithms could correctly identify beam hardening, rings and scatter artifacts.
      Traditional metrics, as well as metrics that describe texture, are needed for the
      classification. Modern linear accelerators are equipped with advanced 2D and 3D
      imaging capabilities that are used for patient alignment, substantially improving
      IGRT treatment accuracy. However, this extra complexity exponentially increases
      the number of QA tests needed. Using the new paradigm described above, not only
      the bare minimum - but also best practice - QA programs could be implemented with
      the same manpower.

PMID- 26219003
TI  - Implementation of an efficient Monte Carlo calculation for CBCT scatter
      correction: phantom study.
AB  - Cone-beam computed tomography (CBCT) images suffer from poor image quality, in a
      large part due to contamination from scattered X-rays. In this work, a Monte
      Carlo (MC)-based iterative scatter correction algorithm was implemented on
      measured phantom data acquired from a clinical on-board CBCT scanner. An
      efficient EGSnrc user code (egs_cbct) was used to transport photons through an
      uncorrected CBCT scan of a Catphan 600 phantom. From the simulation output, the
      contribution from primary and scattered photons was estimated in each projection
      image. From these estimates, an iterative scatter correction was performed on the
      raw CBCT projection data. The results of the scatter correction were compared
      with the default vendor reconstruction. The scatter correction was found to
      reduce the error in CT number for selected regions of interest, while improving
      contrast-to-noise ratio (CNR) by 18%. These results demonstrate the performance
      of the proposed scatter correction algorithm in improving image quality for
      clinical CBCT images.

PMID- 26219004
TI  - Development of an automatic evaluation method for patient positioning error.
AB  - Highly accurate radiotherapy needs highly accurate patient positioning. At our
      facility, patient positioning is manually performed by radiology technicians.
      After the positioning, positioning error is measured by manually comparing some
      positions on a digital radiography image (DR) to the corresponding positions on a
      digitally reconstructed radiography image (DRR). This method is prone to error
      and can be time-consuming because of its manual nature. Therefore, we propose an
      automated measuring method for positioning error to improve patient throughput
      and achieve higher reliability. The error between a position on the DR and a
      position on the DRR was calculated to determine the best matched position using
      the block-matching method. The zero-mean normalized cross correlation was used as
      our evaluation function, and the Gaussian weight function was used to increase
      importance as the pixel position approached the isocenter. The accuracy of the
      calculation method was evaluated using pelvic phantom images, and the method's
      effectiveness was evaluated on images of prostate cancer patients before the
      positioning, comparing them with the results of radiology technicians'
      measurements. The root mean square error (RMSE) of the calculation method for the
      pelvic phantom was 0.23 +/- 0.05 mm. The coefficients between the calculation
      method and the measurement results of the technicians were 0.989 for the phantom
      images and 0.980 for the patient images. The RMSE of the total evaluation results
      of positioning for prostate cancer patients using the calculation method was 0.32
      +/- 0.18 mm. Using the proposed method, we successfully measured residual
      positioning errors. The accuracy and effectiveness of the method was evaluated
      for pelvic phantom images and images of prostate cancer patients. In the future,
      positioning for cancer patients at other sites will be evaluated using the
      calculation method. Consequently, we expect an improvement in treatment
      throughput for these other sites.

PMID- 26219005
TI  - CT protocol management: simplifying the process by using a master protocol
      concept.
AB  - This article explains a method for creating CT protocols for a wide range of
      patient body sizes and clinical indications, using detailed tube current
      information from a small set of commonly used protocols. Analytical expressions
      were created relating CT technical acquisition parameters which can be used to
      create new CT protocols on a given scanner or customize protocols from one
      scanner to another. Plots of mA as a function of patient size for specific
      anatomical regions were generated and used to identify the tube output needs for
      patients as a function of size for a single master protocol. Tube output data
      were obtained from the DICOM header of clinical images from our PACS and patient
      size was measured from CT localizer radiographs under IRB approval. This master
      protocol was then used to create 11 additional master protocols. The 12 master
      protocols were further combined to create 39 single and multiphase clinical
      protocols. Radiologist acceptance rate of exams scanned using the clinical
      protocols was monitored for 12,857 patients to analyze the effectiveness of the
      presented protocol management methods using a two-tailed Fisher's exact test. A
      single routine adult abdominal protocol was used as the master protocol to create
      11 additional master abdominal protocols of varying dose and beam energy.
      Situations in which the maximum tube current would have been exceeded are
      presented, and the trade-offs between increasing the effective tube output via 1)
      decreasing pitch, 2) increasing the scan time, or 3) increasing the kV are
      discussed. Out of 12 master protocols customized across three different scanners,
      only one had a statistically significant acceptance rate that differed from the
      scanner it was customized from. The difference, however, was only 1% and was
      judged to be negligible. All other master protocols differed in acceptance rate
      insignificantly between scanners. The methodology described in this paper allows
      a small set of master protocols to be adapted among different clinical
      indications on a single scanner and among different CT scanners.

PMID- 26219006
TI  - Is 5 mm MMLC suitable for VMAT-based lung SBRT? A dosimetric comparison with 2.5
      mm HDMLC using RTOG-0813 treatment planning criteria for both conventional and
      high-dose flattening filter-free photon beams.
AB  - The aim of this study is to assess the suitability of 5 mm millennium multileaf
      collimator (MMLC) for volumetric-modulated arc therapy (VMAT)-based lung
      stereotactic body radiotherapy (SBRT). Thirty lung SBRT patient treatment plans
      along with their planning target volumes (ranging from 2.01 cc to 150.11 cc) were
      transferred to an inhomogeneous lung phantom and retrospectively planned using
      VMAT technique, along with the high definition multileaf collimator (HDMLC) and
      MMLC systems. The plans were evaluated using Radiation Therapy Oncology Group
      (RTOG-0813) treatment planning criteria for target coverage, normal tissue
      sparing, and treatment efficiency for both the MMLC and HDMLC systems using flat
      and flattening filter-free (FFF) photon beams. Irrespective of the target
      volumes, both the MLC systems were able to satisfy the RTOG-0813 treatment
      planning criteria without having any major deviation. Dose conformity was
      marginally better with HDMLC. The average conformity index (CI) value was found
      to be 1.069 +/- 0.034 and 1.075 +/- 0.0380 for HDMLC and MMLC plans,
      respectively. For the 6 MV FFF beams, the plan was slightly more conformal, with
      the average CI values of 1.063 +/- 0.029 and 1.073 +/- 0.033 for the HDMLC and
      MMLC plans, respectively. The high dose spillage was the maximum for 2 cc volume
      set (3% for HDMLC and 3.1% for MMLC). In the case of low dose spillage, both the
      MLCs were within the protocol of no deviation, except for the 2 cc volume set.
      The results from this study revealed that VMAT-based lung SBRT using 5 mm MMLC
      satisfies the RTOG-0813 treatment planning criteria for the studied target size
      and shapes.

PMID- 26219007
TI  - Clinical experience with two frameless stereotactic radiosurgery (fSRS) systems
      using optical surface imaging for motion monitoring.
AB  - The purpose of this study was to compare two clinical immobilization systems for
      intracranial frameless stereotactic radiosurgery (fSRS) under the same clinical
      procedure using cone-beam computed tomography (CBCT) for setup and video-based
      optical surface imaging (OSI) for initial head alignment and intrafractional
      motion monitoring. A previously established fSRS procedure was applied using two
      intracranial immobilization systems: PinPoint system (head mold and mouthpiece)
      and Freedom system (head mold and open face mask). The CBCT was used for patient
      setup with four degrees of freedom (4DOF), while OSI was used for 6DOF alignment
      prior to CBCT, post-CBCT setup verification at all treatment couch angles (zero
      and nonzero), and intrafractional motion monitoring. Quantitative comparison of
      the two systems includes residual head rotation, head restriction capacity, and
      patient setup time in 25 patients (29 lesions) using PinPoint and 8 patients
      (29fractions) using Freedom. The maximum possible motion was assessed in nine
      volunteers with deliberate, forced movement in Freedom system. A consensus-based
      comparison of patient comfort level and clinical ease of use is reported. Using
      OSI-guided corrections, the maximum residual rotations in all directions were 1.1
      degrees  +/- 0.5 degrees  for PinPoint and 0.6 degrees  +/- 0.3 degrees  for
      Freedom. The time spent performing rotation corrections was 5.0 +/- 4.1 min by
      moving the patient with PinPoint and 2.7 +/- 1.0min by adjusting Freedom couch
      extension. After CBCT, the OSI-CBCT discrepancy due to different anatomic
      landmarks for alignment was 2.4 +/- 1.3 mm using PinPoint and 1.5 +/- 0.7 mm
      using Freedom. Similar results were obtained for setup verification at couch
      angles (< 1.5 mm) and for motion restriction: 0.4+/- 0.3 mm/0.2 degrees  +/- 0.2
      degrees  in PinPoint and 0.6 +/- 0.3 mm/0.3 degrees  +/- 0.1 degrees  in Freedom.
      The maximum range of forced head motion was 2.2 +/- 1.0 mm using Freedom. Both
      intracranial fSRS immobilization systems can restrict head motion within 1.5 mm
      during treatment as monitored by OSI. Setting a motion threshold for beam-hold
      ensures that head motion is constrained within the treatment margin during beam
      on periods. The capability of 6D setup is useful to improve treatment accuracy.
      Patient comfort and clinical workflow should play a substantial role in system
      selection, and Freedom system outperforms PinPoint system in these two aspects.

PMID- 26219008
TI  - Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial
      anthropomorphic phantoms.
AB  - The aims of this study were to characterize reinforced metal-oxide-semiconductor
      field-effect transistor (MOSFET) dosimeters to assess the measurement
      uncertainty, single exposure low-dose limit with acceptable accuracy, and the
      number of exposures required to attain the corresponding limit of the
      thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET
      dosimeter sensitivities for two dental photon energy ranges, dose dependency,
      dose rate dependency, and accumulated dose dependency. A further aim was to
      compare the performance of MOSFETs with those of TLDs in an anthropomorphic
      phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed
      by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET
      dosimeter sensitivities were evaluated for two photon energy ranges (50-90 kVp)
      using a constant dose and polymethylmethacrylate backscatter material. MOSFET and
      TLD comparative point-dose measurements were performed on an anthropomorphic
      phantom that was exposed with a clinical CBCT protocol. The MOSFET single
      exposure low dose limit (25% uncertainty, k = 2) was 1.69 mGy. An averaging of
      eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low
      dose limit. The sensitivity was 3.09 +/- 0.13 mV/mGy independently of the photon
      energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity
      but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated
      threshold voltages between 8300 mV and 17500 mV. The point doses in an
      anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for
      TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was -8%. The
      MOSFET dosimeters presented statistically insignificant energy dependency. By
      averaging multiple exposures, the MOSFET dosimeters can achieve a TLD-comparable
      low-dose limit and constitute a feasible method for diagnostic dosimetry using
      anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the
      sensitivity is too low.

PMID- 26219009
TI  - Investigation of the clinical performance of a novel solid-state diagnostic
      dosimeter.
AB  - This study investigated the clinical performance of a novel solid-state
      diagnostic dosimeter, the RaySafe Xi transparent detector, by comparing its
      performance to a reference-class ionization chamber. Firstly a comparison of
      dosimeter response "free-in-air" with standard beam qualities was made, followed
      by an investigation into its relative transparency in an X-ray field and angular
      sensitivity dependence. The second part of the study looked at the overall
      performance of the transparent detector under scatter conditions with a number of
      beam qualities, including standard beam and those hardened by copper (Cu)
      filtration of thickness up to 0.9 mm, as would be encountered in the equipment
      testing of fluoroscopy systems. Overall, the transparent detector has
      demonstrated equivalent measurement properties to the ionization chamber under
      standard conditions and provided similar X-ray attenuation as reflected by the
      nearly identical radiographic parameters selected for both dosimeters by the
      automatic dose rate control (ADRC) system. Yet, it also possessed an asymmetric
      angular response which respectively under- and overestimated the dose
      contribution from the rear and lateral directions by the same amount of 50%. The
      transparent detector provided comparable dose reading of +/- 3% to the ionization
      chamber with standard beam qualities and backscatter radiation present. These
      results were in good agreement with those of free-in-air measurement, indicating
      that the angular under- and overresponse might potentially compensate one another
      for accurate measurement. However, for identical Cu filtered beam qualities and
      setups, the transparent detector on average overresponded by 5.4% across the
      useful tube voltage range. In conclusion, the transparent detector, with its
      novel design, is essentially equivalent, within a 5% tolerance, to an ionization
      chamber, except in situations where beams hardened with Cu filtration are used
      with backscatter radiation present requiring larger uncertainty error
      estimations.

PMID- 26219010
TI  - Generation and verification of QFix kVue Calypso-compatible couch top model for a
      dedicated stereotactic linear accelerator with FFF beams.
AB  - This study details the generation, verification, and implementation of a
      treatment planning system (TPS) couch top model for patient support system used
      in conjunction with a dedicated stereotactic linear accelerator. Couch top model
      was created within the TPS using CT simulation images of the kVue Calpyso
      compatible couchtop (with rails). Verification measurements were compared to TPS
      dose prediction for different energies (6 MV FFF and 10 MV FFF) and rail
      configurations (rails in and rails out) using: 1) central axis point-dose
      measurements with pinpoint chamber in water-equivalent phantom at 42 gantry
      angles for various field sizes (2 * 2 cm2, 4 * 4 cm2, 10 * 10 cm2); and 2)
      Gafchromic EBT3 film parallel to beam in acrylic slab to assess changes in
      surface and percent depth doses in PA geometry. To assess sensitivity of
      delivered dose to variations in patient lateral position, measurements at central
      axis using the pinpoint chamber geometry were taken at lateral couch
      displacements of 2, 5, and 10 mm for 6 MV FFF. The maximum percent difference for
      point-dose measurements was 3.24% (6 MV FFF) and 2.30% (10 MV FFF). The average
      percent difference for point-dose measurements was less than 1.10% for all beam
      energies and rail geometries. The maximum percent difference between calculated
      and measured dose can be as large as 13.0% if no couch model is used for dose
      calculation. The presence of the couch structures also impacts surface dose and
      PDD, which was evaluated with Gafchromic film measurements. The upstream shift in
      the depth of dose maximum (dmax) was found to be 10.5 mm for 6 MV FFF and 5.5 mm
      for 10 MV FFF for 'Rails In' configuration. Transmission of the treatment beam
      through the couch results in an increase in surface dose (absolute percentage) of
      approximately 50% for both photon energies (6 MV FFF and 10MV FFF). The largest
      sensitivity to lateral shifts occurred at the lateral boundary of the rail
      structures. The mean magnitude (standard deviation) of the deviation between
      shifted and centered measurements over all field sizes tested was 0.61% (0.61%)
      for 2 mm shifts, 0.46% (0.67%) for 5 mm shifts, and 0.86% (1.46%) for 10 mm
      shifts.

PMID- 26219011
TI  - Influence of internal fixation systems on radiation therapy for spinal tumor.
AB  - In this study, the influence of internal fixation systems on radiation therapy
      for spinal tumor was investigated in order to derive a theoretical basis for
      adjustment of radiation dose for patients with spinal tumor and internal
      fixation. Based on a common method of internal fixation after resection of spinal
      tumor, different models of spinal internal fixation were constructed using the
      lumbar vertebra of fresh domestic pigs and titanium alloy as the internal
      fixation system. Variations in radiation dose in the vertebral body and partial
      spinal cord in different types of internal fixation were studied under the same
      radiation condition (6 MV and 600 mGy) in different fixation models and compared
      with those irradiated based on the treatment planning system (TPS). Our results
      showed that spinal internal fixation materials have great impact on the radiation
      dose absorbed by spinal tumors. Under the same radiation condition, the influence
      of anterior internal fixation material or combined anterior and posterior
      approach on radiation dose at the anterior border of the vertebral body was the
      greatest. Regardless of the kinds of internal fixation method employed, radiation
      dose at the anterior border of the vertebral body was significantly different
      from that at other positions. Notably, the influence of posterior internal
      fixation material on the anterior wall of the vertebral canal was the greatest. X
      ray attenuation and scattering should be taken into consideration for most
      patients with bone metastasis that receive fixation of metal implants. Further
      evaluation should then be conducted with modified TPS in order to minimize the
      potentially harmful effects of inappropriate radiation dose.

PMID- 26219012
TI  - Quality control of CT systems by automated monitoring of key performance
      indicators: a two-year study.
AB  - The purpose of this study was to develop a method of performing routine
      periodical quality controls (QC) of CT systems by automatically analyzing key
      performance indicators (KPIs), obtainable from images of manufacturers' quality
      assurance (QA) phantoms. A KPI pertains to a measurable or determinable QC
      parameter that is influenced by other underlying fundamental QC parameters. The
      established KPIs are based on relationships between existing QC parameters used
      in the annual testing program of CT scanners at the Karolinska University
      Hospital in Stockholm, Sweden. The KPIs include positioning, image noise,
      uniformity, homogeneity, the CT number of water, and the CT number of air. An
      application (MonitorCT) was developed to automatically evaluate phantom images in
      terms of the established KPIs. The developed methodology has been used for two
      years in clinical routine, where CT technologists perform daily scans of the
      manufacturer's QA phantom and automatically send the images to MonitorCT for KPI
      evaluation. In the cases where results were out of tolerance, actions could be
      initiated in less than 10 min. 900 QC scans from two CT scanners have been
      collected and analyzed over the two-year period that MonitorCT has been active.
      Two types of errors have been registered in this period: a ring artifact was
      discovered with the image noise test, and a calibration error was detected
      multiple times with the CT number test. In both cases, results were outside the
      tolerances defined for MonitorCT, as well as by the vendor. Automated monitoring
      of KPIs is a powerful tool that can be used to supplement established QC
      methodologies. Medical physicists and other professionals concerned with the
      performance of a CT system will, using such methods, have access to comprehensive
      data on the current and historical (trend) status of the system such that swift
      actions can be taken in order to ensure the quality of the CT examinations,
      patient safety, and minimal disruption of service.

PMID- 26219013
TI  - Robotic radiosurgery system patient-specific QA for extracranial treatments using
      the planar ion chamber array and the cylindrical diode array.
AB  - Robotic radiosurgery system has been increasingly employed for extracranial
      treatments. This work is aimed to study the feasibility of a cylindrical diode
      array and a planar ion chamber array for patient-specific QA with this robotic
      radiosurgery system and compare their performance. Fiducial markers were
      implanted in both systems to enable image-based setup. An in-house program was
      developed to postprocess the movie file of the measurements and apply the beam-by
      beam angular corrections for both systems. The impact of noncoplanar delivery was
      then assessed by evaluating the angles created by the incident beams with respect
      to the two detector arrangements and cross-comparing the planned dose
      distribution to the measured ones with/without the angular corrections. The
      sensitivity of detecting the translational (1-3 mm) and the rotational (1 degrees
      -3 degrees ) delivery errors were also evaluated for both systems. Six
      extracranial patient plans (PTV 7-137 cm3) were measured with these two systems
      and compared with the calculated doses. The plan dose distributions were
      calculated with ray-tracing and the Monte Carlo (MC) method, respectively. With
      0.8 by 0.8 mm2 diodes, the output factors measured with the cylindrical diode
      array agree better with the commissioning data. The maximum angular correction
      for a given beam is 8.2% for the planar ion chamber array and 2.4% for the
      cylindrical diode array. The two systems demonstrate a comparable sensitivity of
      detecting the translational targeting errors, while the cylindrical diode array
      is more sensitive to the rotational targeting error. The MC method is necessary
      for dose calculations in the cylindrical diode array phantom because the ray
      tracing algorithm fails to handle the high-Z diodes and the acrylic phantom. For
      all the patient plans, the cylindrical diode array/ planar ion chamber array
      demonstrate 100% / > 92% (3%/3 mm) and > 96% / ~ 80% (2%/2 mm) passing rates. The
      feasibility of using both systems for robotic radiosurgery system patient
      specific QA has been demonstrated. For gamma evaluation, 2%/2 mm criteria for
      cylindrical diode array and 3%/3 mm criteria for planar ion chamber array are
      suggested. The customized angular correction is necessary as proven by the
      improved passing rate, especially with the planar ion chamber array system.

PMID- 26219014
TI  - Dosimetric comparison of Acuros XB with collapsed cone convolution/superposition
      and anisotropic analytic algorithm for stereotactic ablative radiotherapy of
      thoracic spinal metastases.
AB  - The aim of this study is to compare the recent Eclipse Acuros XB (AXB) dose
      calculation engine with the Pinnacle collapsed cone convolution/superposition
      (CCC) dose calculation algorithm and the Eclipse anisotropic analytic algorithm
      (AAA) for stereotactic ablative radiotherapy (SAbR) treatment planning of
      thoracic spinal (T-spine) metastases using IMRT and VMAT delivery techniques. The
      three commissioned dose engines (CCC, AAA, and AXB) were validated with ion
      chamber and EBT2 film measurements utilizing a heterogeneous slab-geometry water
      phantom and an anthropomorphic phantom. Step-and-shoot IMRT and VMAT treatment
      plans were developed and optimized for eight patients in Pinnacle, following our
      institutional SAbR protocol for spinal metastases. The CCC algorithm, with
      heterogeneity corrections, was used for dose calculations. These plans were then
      exported to Eclipse and recalculated using the AAA and AXB dose calculation
      algorithms. Various dosimetric parameters calculated with CCC and AAA were
      compared to that of the AXB calculations. In regions receiving above 50% of
      prescription dose, the calculated CCC mean dose is 3.1%-4.1% higher than that of
      AXB calculations for IMRT plans and 2.8%-3.5% higher for VMAT plans, while the
      calculated AAA mean dose is 1.5%-2.4% lower for IMRT and 1.2%-1.6% lower for
      VMAT. Statistically significant differences (p < 0.05) were observed for most GTV
      and PTV indices between the CCC and AXB calculations for IMRT and VMAT, while
      differences between the AAA and AXB calculations were not statistically
      significant. For T-spine SAbR treatment planning, the CCC calculations give a
      statistically significant overestimation of target dose compared to AXB. AAA
      underestimates target dose with no statistical significance compared to AXB.
      Further study is needed to determine the clinical impact of these findings.

PMID- 26219015
TI  - Comparison of measured Varian Clinac 21EX and TrueBeam accelerator electron field
      characteristics.
AB  - Dosimetric comparisons of radiation fields produced by Varian's newest linear
      accelerator, the TrueBeam, with those produced by older Varian accelerators are
      of interest from both practical and research standpoints. While photon fields
      have been compared in the literature, similar comparisons of electron fields have
      not yet been reported. In this work, electron fields produced by the TrueBeam are
      compared with those produced by Varian's Clinac 21EX accelerator. Diode
      measurements were taken of fields shaped with electron applicators and delivered
      at 100 cm SSD, as well as those shaped with photon MLCs without applicators and
      delivered at 70 cm SSD for field sizes ranging from 5 * 5 to 25 * 25 cm2 at
      energies between 6 and 20 MeV. Additionally, EBT2 and EBT3 radio-chromic film
      measurements were taken of an MLC-shaped aperture with closed leaf pairs
      delivered at 70 cm SSD using 6 and 20 MeV electrons. The 6 MeV fields produced by
      the TrueBeam and Clinac 21EX were found to be almost indistinguishable. At higher
      energies, TrueBeam fields shaped by electron applicators were generally flatter
      and had less photon contamination compared to the Clinac 21EX. Differences in
      PDDs and profiles fell within 3% and 3 mm for the majority of measurements. The
      most notable differences for open fields occurred in the profile shoulders for
      the largest applicator field sizes. In these cases, the TrueBeam and Clinac 21EX
      data differed by as much as 8%. Our data indicate that an accurate electron beam
      model of the Clinac 21EX could be used as a starting point to simulate electron
      fields that are dosimetrically equivalent to those produced by the TrueBeam.
      Given that the Clinac 21EX shares head geometry with Varian's iX, Trilogy, and
      Novalis TX accelerators, our findings should also be applicable to these
      machines.

PMID- 26219016
TI  - Re: JACMP Editorial: The meaning of the MS Degree in Medical Physics, Part 4.

PMID- 26219018
TI  - De novo sequencing and characterization of the Bradysia odoriphaga (Diptera:
      Sciaridae) larval transcriptome.
AB  - The most serious pestilent threat to the Chinese chive, Allium tuberosum Rottle
      ex Spreng (Liliaceae) is the Bradysia odoriphaga Yang and Zhang. There is limited
      genetic research focused on B. odoriphaga, partially due to the lack of genomic
      resources. The advent of high-throughput sequencing technologies has enabled
      generation of genomic resources in a short time frame and at minimal costs. In
      this study, we performed, for the first time, de novo transcriptome sequencing of
      the B. odoriphaga. Here, 16,829 unigenes were assembled from the total reads,
      12,024 of these unigenes were annotated in the NCBI NR protein database, and 9784
      were annotated in the Swiss-Prot database. Of these annotated unigenes, 7903 and
      5060 unigenes have been assigned to gene ontology categories and clusters of
      orthologous groups, respectively. Furthermore, 8647 unigenes were mapped to 257
      pathways using the Kyoto Encyclopedia of Genes and Genomes Pathway database. We
      found that 408 unigenes were related to insecticide resistance and metabolism. In
      addition, 23,122 simple sequence repeats (SSRs) were identified in 11,009
      unigenes, and 100 PCR primers of SSR loci were used to validate the assembly
      quality and polymorphisms. These results provide a good platform for further
      investigations into the insecticide resistance of B. odoriphaga. Finally, the
      SSRs identified in B. odoriphaga may be a useful genomic resource. 

PMID- 26219019
TI  - Fluorescent difluoroboron-curcumin analogs: An investigation of the electronic
      structures and photophysical properties.
AB  - A comprehensive approach based on the density functional theory method was used
      to elicit the molecular and photophysical properties of four difluoroboron
      analogs of curcumin. The ground state geometry optimization, vertical absorption
      and the first excited state optimization were carried out using the B3LYP/6
      31G(d) method. The geometry of the molecules remains planar both in the ground
      and excited states. There is a good correlation between the observed absorption
      (maximum deviation of 8%) and emission wavelength (maximum deviation of 22%) with
      the computed values. Different polarizability parameters were computed and
      compared with urea. The values obtained for the difluoroboron dyes are larger
      than those of urea, suggesting considerable charge transfer characteristics of
      the first excited state. This is further supported by the significant difference
      in the dipole moment. The outcome of this work should be useful towards the
      industrial applications of these curcumin-based dyes.

PMID- 26219020
TI  - Structural and vibrational studies on 1-(5-methyl-[1,3,4] thiadiazol-2-yl)
      pyrolidin-2-ol.
AB  - FT-Raman and FT-IR spectra were recorded for1-(5-methyl-[1,3,4]thiadiazol-2-yl)
      pyrolidin-2-ol (MTPN) sample in solid state. The equilibrium geometries, harmonic
      vibrational frequencies, IR and the Raman scattering intensities were computed
      using DFT/6-311++G (d,p) level. Results obtained at this level of theory were
      used for a detailed interpretation of the IR and Raman spectra, based on the TED
      of the normal modes. Molecular parameters such as bond lengths, bond angles and
      dihedral angles were calculated. The intra-molecular charge transfer was
      calculated by means of NBO. Hyperconjugative interaction energy was more during
      the pi-pi(*) transition. Energy gap of the molecule has been found using HOMO and
      LUMO calculation, hence the less band gap, which seems to be more stable.

PMID- 26219021
TI  - Molecular structure and vibrational spectroscopic studies of prothionamide by
      density functional theory.
AB  - Prothionamide (PTH) is the secondary drug used against Mycobacterium tuberculosis
      bacteria and leprosy. The aim of this work was to investigate the potential
      energy surface map, anharmonic and harmonic vibrational spectra, NBO analysis and
      ELF (Electron Localization Function) of the title compound using DFT approach
      with the B3LYP (Becke, three-parameter, Lee-Yang-Parr) exchange-correlation
      functional with the 6-31G++(d,p) and the Z3POLX basis sets were employed. In the
      experimental part of this study, FT-Mid IR, FT-Far IR and FT-Raman spectra of the
      molecule were recorded in the regions 4000-450cm(-1), 700-30cm(-1) and 4000
      100cm(-1) respectively in the solid phase. The comparison between calculated and
      experimental vibrational spectra (infrared and Raman spectra) and assignments of
      fundamental vibrational modes were characterized by total energy distribution
      (TED). Theoretical spectra were seen to be in good agreement with those of the
      experimental ones.

PMID- 26219022
TI  - Improving the stability of peptidic radiotracers by the introduction of
      artificial scaffolds: which structure element is most useful?
AB  - Peptidic radiotracers are highly potent substances for the specific in vivo
      imaging of various biological targets with Single Photon Emission Computed
      Tomography and Positron Emission Tomography. However, some radiolabeled peptides
      such as bombesin analogs were shown to exhibit only a limited stability,
      hampering a successful target visualization. One option to positively influence
      the stability of radiolabeled peptides is the introduction of certain artificial
      molecular scaffolds. In order to comparatively assess the influence of different
      structure elements on the stability of radiolabeled peptides and to identify
      those structure elements being most useful for peptide radiotracer stabilization,
      several monomeric and dimeric bombesin derivatives were synthesized, exhibiting
      differing molecular designs and the chelator NODAGA for (68) Ga-labeling. The
      radiolabeled peptides were evaluated regarding their in vitro stability in human
      serum to determine the influence of the introduced molecular scaffolds on the
      peptides' serum stabilities. The results of the evaluations showed that the
      introduction of scaffold structures and the overall molecular design have a
      substantial impact on the stabilities of the resulting peptidic radiotracers. But
      besides some general trends found using certain scaffold structures, the obtained
      results point to the necessity to empirically assess their influence on stability
      for each susceptible peptidic radiotracer individually. 

PMID- 26219023
TI  - Characterization of Escherichia coli-Producing Extended-Spectrum beta-Lactamase
      (ESBL) Isolated from Chicken Slaughterhouses in South Korea.
AB  - In South Korea, few reports have indicated the occurrence and characteristics of
      extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in food
      producing animals, particularly in poultry slaughterhouses. In this study, we
      investigated the occurrence and antibiotic resistance of ESBL-producing E. coli
      from whole chicken carcasses (n=156) and fecal samples (n=39) of chickens
      obtained from 2 slaughterhouses. Each sample enriched in buffered peptone water
      was cultured on MacConkey agar with 2 mg/L cefotaxime and ESBL agar. ESBL
      production and antibiotic susceptibility were determined using the Trek
      Diagnostics system. The ESBL genotypes were determined by polymerase chain
      reaction (PCR) using the bla(SHV), bla(TEM), and bla(CTX-M) gene sequences.
      Subtyping using a repetitive sequence-based PCR system (DiversiLabTM) and
      multilocus sequence typing (MLST) were used to assess the interspecific
      biodiversity of isolates. Sixty-two ESBL-producing E. coli isolates were obtained
      from 156 samples (39.7%). No bla(SHV) genes were detected in any of the isolates,
      whereas all contained the bla(TEM) gene. Twenty-five strains (40.3%) harbored the
      CTX-M group 1 gene. The most prevalent MLST sequence type (ST) was ST 93 (14.5%),
      followed by ST 117 (9.7%) and ST 2303 (8.1%). This study reveals a high
      occurrence and beta-lactams resistance rate of E. coli in fecal samples and whole
      chickens collected from slaughterhouses in South Korea.

PMID- 26219024
TI  - DFT Study of Oxygen Dissociation in Molten Carbonate.
AB  - Using density functional theory method, we have studied the oxygen dissociation
      in alkali molten carbonate at the B3LYP/6-31G(d) level. The calculated energies
      were then verified by MP4 and CCSD(T). A four-formula cluster (M2CO3)4, M = Li,
      Na, and K was used to describe the molten carbonate. It was found that the
      adsorption of oxygen to molten carbonate is of a chemical type and leads to the
      formation of CO5(2-) in MC, which was confirmed for the first time by DFT
      calculations. The energy barrier for its dissociation is calculated to be 197.9,
      116.7, and 170.3 kJ/mol in the (M2CO3)4 cluster, M = Li, Na, and K, respectively.
      If the reaction of O2 + 2CO3(2-) -> 2CO4(2-) is approximated as a one-step
      reaction, the activation energy is estimated to be 96.2, 15.1, and 68.6 kJ/mol,
      respectively. The reaction rate is first order to the pressure of oxygen.
      Surprisingly, the reaction of oxygen dissociation has the lowest energy barrier
      in sodium carbonate, which is consistent with the recent experimental findings.
      It is very clear that the molten carbonate salt has directly participated in the
      ORR process and plays an important role as a catalyst in the cathode of SOFCs.
      The oxygen reduction has been facilitated by MC and enhanced cell performance has
      been observed. 

PMID- 26219026
TI  - Influence of Hamstring Fatigue on the Estimated Percentage of Fast-Twitch Muscle
      Fibers for the Vastus Lateralis.
AB  - A previous study has demonstrated the ability to roughly estimate the percentage
      of fast-twitch muscle fibers for the vastus lateralis through the analysis of
      peak torque values during fatiguing isokinetic testing. We examined whether use
      of the hamstrings influenced peak torque and electromyographic (EMG) responses
      for the quadriceps during fatiguing isokinetic muscle actions. On 2 separate
      occasions, 21 men (mean age = 23 years) performed 50 repeated, maximal concentric
      isokinetic muscle actions of the left leg extensors at a velocity of 180 degrees
      .s. For 1 trial, the subjects maximally flexed the knee joint after each full
      extension to bring the dynamometer's lever arm back to the starting position. For
      the other trial, the subjects relaxed after each maximal extension and an
      investigator assisted in returning the lever arm. Surface EMG signals were
      detected from the vastus lateralis and biceps femoris throughout testing.
      Dependent variables that assessed the decline in peak torque and EMG mean
      frequency for the vastus lateralis were examined using dependent samples t-tests,
      effect size statistics, and the number of subjects who exceeded the minimal
      difference needed to be considered real. Our results showed small mean
      differences between the trials (Cohen's d <=0.136). For the estimated percentage
      of fast-twitch fibers, none of the subjects showed a difference between trials
      that we considered meaningful. The mean estimated percentages of fast-twitch
      fibers were 61.6 and 60.1. Collectively, use of the hamstrings during fatiguing
      isokinetic testing of the quadriceps had little influence on peak torque and EMG.

PMID- 26219027
TI  - Selectivity and Cooperativity in the Binding of Multiple Guests to a
      Pillar[5]arene-Crown Ether Fused Tricyclic Host.
AB  - A novel tricylic host molecule 1 that consists of two pillar[5]arene units and a
      crown ether ring was found to selectively bind two kinds of guest molecules with
      different shapes, sizes, and electronic constitutions, namely 1,4-dicyanobutane
      G1 and paraquat G2, with its two macrocyclic subunits, to form a four-component
      complex 2G1?1?G2. An (1)H NMR study of stepwise bindings of G1 and G2 to host 1
      in CDCl3/DMSO-d6 revealed that the strength of the association between complex
      2G1?1 and guest G2 was only one-fourth of that between free 1 and G2,
      demonstrating a negative heterotropic cooperativity of G1 in the binding of G2 to
      host 1. 

PMID- 26219030
TI  - Portrait of My Teacher, Fraulein Sophie von Prieser: Florine Stettheimer.

PMID- 26219031
TI  - Medicare at 50: Reflections From Former CMS Administrator Donald M. Berwick.

PMID- 26219032
TI  - Medicaid at 50: Time for a Major Overhaul.

PMID- 26219043
TI  - Strengthening the Affordable Care Act: The Need for Strategic Building Blocks.

PMID- 26219044
TI  - From the Affordable Care Act to Affordable Care.

PMID- 26219045
TI  - Improving and Refining the Affordable Care Act.

PMID- 26219047
TI  - Medicaid's New Role in the Health Care System.

PMID- 26219046
TI  - Outlook for Alternative Payment Models in Fee-for-Service Medicare.

PMID- 26219048
TI  - Managing the Future of Medicaid.

PMID- 26219049
TI  - The Medicare Hospital Readmissions Reduction Program: Time for Reform.

PMID- 26219050
TI  - State Leadership in Health Care Transformation: Red and Blue.

PMID- 26219051
TI  - A PIECE OF MY MIND. Running a Code in My Ice Skates, and Other Tales.

PMID- 26219052
TI  - Medicare and Medicaid, the Affordable Care Act, and US Health Policy.

PMID- 26219053
TI  - Mortality, Hospitalizations, and Expenditures for the Medicare Population Aged 65
      Years or Older, 1999-2013.
AB  - IMPORTANCE: In a period of dynamic change in health care technology, delivery,
      and behaviors, tracking trends in health and health care can provide a
      perspective on what is being achieved. OBJECTIVE: To comprehensively describe
      national trends in mortality, hospitalizations, and expenditures in the Medicare
      fee-for-service population between 1999 and 2013. DESIGN, SETTING, AND
      PARTICIPANTS: Serial cross-sectional analysis of Medicare beneficiaries aged 65
      years or older between 1999 and 2013 using Medicare denominator and inpatient
      files. MAIN OUTCOMES AND MEASURES: For all Medicare beneficiaries, trends in all
      cause mortality; for fee-for-service beneficiaries, trends in all-cause
      hospitalization and hospitalization-associated outcomes and expenditures.
      Geographic variation, stratified by key demographic groups, and changes in the
      intensity of care for fee-for-service beneficiaries in the last 1, 3, and 6
      months of life were also assessed. RESULTS: The sample consisted of 68,374,904
      unique Medicare beneficiaries (fee-for-service and Medicare Advantage). All-cause
      mortality for all Medicare beneficiaries declined from 5.30% in 1999 to 4.45% in
      2013 (difference, 0.85 percentage points; 95% CI, 0.83-0.87). Among fee-for
      service beneficiaries (n = 60,056,069), the total number of hospitalizations per
      100,000 person-years decreased from 35,274 to 26,930 (difference, 8344; 95% CI,
      8315-8374). Mean inflation-adjusted inpatient expenditures per Medicare fee-for
      service beneficiary declined from $3290 to $2801 (difference, $489; 95% CI, $487
      $490). Among fee-for-service beneficiaries in the last 6 months of life, the
      number of hospitalizations decreased from 131.1 to 102.9 per 100 deaths
      (difference, 28.2; 95% CI, 27.9-28.4). The percentage of beneficiaries with 1 or
      more hospitalizations decreased from 70.5 to 56.8 per 100 deaths (difference,
      13.7; 95% CI, 13.5-13.8), while the inflation-adjusted inpatient expenditure per
      death increased from $15,312 in 1999 to $17,423 in 2009 and then decreased to
      $13,388 in 2013. Findings were consistent across geographic and demographic
      groups. CONCLUSIONS AND RELEVANCE: Among Medicare fee-for-service beneficiaries
      aged 65 years or older, all-cause mortality rates, hospitalization rates, and
      expenditures per beneficiary decreased from 1999 to 2013. In the last 6 months of
      life, total hospitalizations and inpatient expenditures decreased in recent
      years.

PMID- 26219054
TI  - Changes in Self-reported Insurance Coverage, Access to Care, and Health Under the
      Affordable Care Act.
AB  - IMPORTANCE: The Affordable Care Act (ACA) completed its second open enrollment
      period in February 2015. Assessing the law's effects has major policy
      implications. OBJECTIVES: To estimate national changes in self-reported coverage,
      access to care, and health during the ACA's first 2 open enrollment periods and
      to assess differences between low-income adults in states that expanded Medicaid
      and in states that did not expand Medicaid. DESIGN, SETTING, AND PARTICIPANTS:
      Analysis of the 2012-2015 Gallup-Healthways Well-Being Index, a daily national
      telephone survey. Using multivariable regression to adjust for pre-ACA trends and
      sociodemographics, we examined changes in outcomes for the nonelderly US adult
      population aged 18 through 64 years (n = 507,055) since the first open enrollment
      period began in October 2013. Linear regressions were used to model each outcome
      as a function of a linear monthly time trend and quarterly indicators. Then, pre
      ACA (January 2012-September 2013) and post-ACA (January 2014-March 2015) changes
      for adults with incomes below 138% of the poverty level in Medicaid expansion
      states (n = 48,905 among 28 states and Washington, DC) vs nonexpansion states (n
      = 37,283 among 22 states) were compared using a differences-in-differences
      approach. EXPOSURES: Beginning of the ACA's first open enrollment period (October
      2013). MAIN OUTCOMES AND MEASURES: Self-reported rates of being uninsured,
      lacking a personal physician, lacking easy access to medicine, inability to
      afford needed care, overall health status, and health-related activity
      limitations. RESULTS: Among the 507,055 adults in this survey, pre-ACA trends
      were significantly worsening for all outcomes. Compared with the pre-ACA trends,
      by the first quarter of 2015, the adjusted proportions who were uninsured
      decreased by 7.9 percentage points (95% CI, -9.1 to -6.7); who lacked a personal
      physician, -3.5 percentage points (95% CI, -4.8 to -2.2); who lacked easy access
      to medicine, -2.4 percentage points (95% CI, -3.3 to -1.5); who were unable to
      afford care, -5.5 percentage points (95% CI, -6.7 to -4.2); who reported
      fair/poor health, -3.4 percentage points (95% CI, -4.6 to -2.2); and the
      percentage of days with activities limited by health, -1.7 percentage points (95%
      CI, -2.4 to -0.9). Coverage changes were largest among minorities; for example,
      the decrease in the uninsured rate was larger among Latino adults (-11.9
      percentage points [95% CI, -15.3 to -8.5]) than white adults (-6.1 percentage
      points [95% CI, -7.3 to -4.8]). Medicaid expansion was associated with
      significant reductions among low-income adults in the uninsured rate (differences
      in-differences estimate, -5.2 percentage points [95% CI, -7.9 to -2.6]), lacking
      a personal physician (-1.8 percentage points [95% CI, -3.4 to -0.3]), and
      difficulty accessing medicine (-2.2 percentage points [95% CI, -3.8 to -0.7]).
      CONCLUSIONS AND RELEVANCE: The ACA's first 2 open enrollment periods were
      associated with significantly improved trends in self-reported coverage, access
      to primary care and medications, affordability, and health. Low-income adults in
      states that expanded Medicaid reported significant gains in insurance coverage
      and access compared with adults in states that did not expand Medicaid.

PMID- 26219055
TI  - Hospital Characteristics Associated With Penalties in the Centers for Medicare &
      Medicaid Services Hospital-Acquired Condition Reduction Program.
AB  - IMPORTANCE: In fiscal year (FY) 2015, the Centers for Medicare & Medicaid
      Services (CMS) instituted the Hospital-Acquired Condition (HAC) Reduction
      Program, which reduces payments to the lowest-performing hospitals. However, it
      is uncertain whether this program accurately measures quality and fairly
      penalizes hospitals. OBJECTIVE: To examine the characteristics of hospitals
      penalized by the HAC Reduction Program and to evaluate the association of a
      summary score of hospital characteristics related to quality with penalization in
      the HAC program. DESIGN, SETTING, AND PARTICIPANTS: Data for hospitals
      participating in the FY2015 HAC Reduction Program were obtained from CMS'
      Hospital Compare and merged with the 2014 American Hospital Association Annual
      Survey and FY2015 Medicare Impact File. Logistic regression models were developed
      to examine the association between hospital characteristics and HAC program
      penalization. An 8-point hospital quality summary score was created using
      hospital characteristics related to volume, accreditations, and offering of
      advanced care services. The relationship between the hospital quality summary
      score and HAC program penalization was examined. Publicly reported process-of
      care and outcome measures were examined from 4 clinical areas (surgery, acute
      myocardial infarction, heart failure, pneumonia), and their association with the
      hospital quality summary score was evaluated. EXPOSURES: Penalization in the HAC
      Reduction Program. MAIN OUTCOMES AND MEASURES: Hospital characteristics
      associated with penalization. RESULTS: Of the 3284 hospitals participating in the
      HAC program, 721 (22.0%) were penalized. Hospitals were more likely to be
      penalized if they were accredited by the Joint Commission (24.0% accredited,
      14.4% not accredited; odds ratio [OR], 1.33; 95% CI, 1.04-1.70); they were major
      teaching hospitals (42.3%; OR, 1.58; 95% CI, 1.09-2.29) or very major teaching
      hospitals (62.2%; OR, 2.61; 95% CI, 1.55-4.39; vs nonteaching hospitals, 17.0%);
      they cared for more complex patient populations based on case mix index (quartile
      4 vs quartile 1: 32.8% vs 12.1%; OR, 1.98; 95% CI, 1.44-2.71); or they were
      safety-net hospitals vs non-safety-net hospitals (28.3% vs 19.9%; OR, 1.36; 95%
      CI, 1.11-1.68). Hospitals with higher hospital quality summary scores had
      significantly better performance on 9 of 10 publicly reported process and
      outcomes measures compared with hospitals that had lower quality scores (all P <=
      .01 for trend). However, hospitals with the highest quality score of 8 were
      penalized significantly more frequently than hospitals with the lowest quality
      score of 0 (67.3% [37/55] vs 12.6% [53/422]; P < .001 for trend). CONCLUSIONS AND
      RELEVANCE: Among hospitals participating in the HAC Reduction Program, hospitals
      that were penalized more frequently had more quality accreditations, offered
      advanced services, were major teaching institutions, and had better performance
      on other process and outcome measures. These paradoxical findings suggest that
      the approach for assessing hospital penalties in the HAC Reduction Program merits
      reconsideration to ensure it is achieving the intended goals.

PMID- 26219056
TI  - Medicare and Medicaid at 50 Years: Perspectives of Beneficiaries, Health Care
      Professionals and Institutions, and Policy Makers.
AB  - IMPORTANCE: Medicare and Medicaid are the nation's 2 largest public health
      insurance programs, serving the elderly, those with disabilities, and mostly
      lower-income populations. The 2 programs are the focus of often deep partisan
      disagreement. Medicare and Medicaid payment policies influence the health care
      system and Medicare and Medicaid spending influences federal and state budgets.
      Debate about Medicare and Medicaid policy sometimes influences elections.
      OBJECTIVE: To review the roles of Medicare and Medicaid in the health system and
      the challenges the 2 programs face from the perspectives of the general public
      and beneficiaries, health care professionals and health care institutions, and
      policy makers. EVIDENCE: Analysis of publicly available data and private surveys
      of the public and beneficiaries. FINDINGS: Together, Medicare and Medicaid serve
      111 million beneficiaries and account for $1 trillion in total spending,
      generating 43% of hospital revenue and representing 39% of national health
      spending. The median income for Medicare beneficiaries is $23,500 and the median
      income for Medicaid beneficiaries is $15,000. Future issues confronting both
      programs include whether they will remain open-ended entitlements, the degree to
      which the programs may be privatized, the scope of their cost-sharing structures
      for beneficiaries, and the roles the programs will play in payment and delivery
      reform. CONCLUSIONS AND RELEVANCE: As the number of beneficiaries and the amount
      of spending for both Medicare and Medicaid increase, these programs will remain a
      focus of national attention and policy debate. Beneficiaries, health care
      professionals, health care organizations, and policy makers often have different
      interests in Medicare and Medicaid, complicating efforts to make changes to these
      large programs.

PMID- 26219057
TI  - Empirical Therapy of Community-Acquired Pneumonia: Advancing Evidence or Just
      More Doubt?

PMID- 26219058
TI  - Healthy Lifestyle Counseling in Persons With Cardiovascular Risk Factors.

PMID- 26219059
TI  - Fever and Rash in a Patient With Hepatitis.

PMID- 26219060
TI  - Outpatient Pharmacy Expenditures for Children With Serious Chronic Illness in
      California, 2010-2012.

PMID- 26219061
TI  - Surrogate Decision Making for Patients Without Nuclear Family.

PMID- 26219062
TI  - Maternal Diabetes and Autism in Offspring.

PMID- 26219063
TI  - Maternal Diabetes and Autism in Offspring--Reply.

PMID- 26219064
TI  - Potential Adverse Effects of Anesthesia in Children.

PMID- 26219065
TI  - Surrogate Decision Making for Patients Without Nuclear Family.

PMID- 26219066
TI  - Potential Adverse Effects of Anesthesia in Children--Reply.

PMID- 26219068
TI  - Medicare: Theory and Practice.

PMID- 26219069
TI  - JAMA PATIENT PAGE. Medicare.

PMID- 26219070
TI  - Dynamic modeling predicts continued bioaccumulation of polybrominated diphenyl
      ethers (PBDEs) in smallmouth bass (Micropterus dolomiu) post phase-out due to
      invasive prey and shifts in predation.
AB  - Unprecedented food chain links between benthic and pelagic organisms are often
      thought to disrupt traditional contaminant transport and uptake due to changes in
      predation and mobilization of otherwise sequestered pollutants. A bioaccumulation
      model for polybrominated diphenyl ethers (PBDEs) is developed to simulate
      increases in biotic congener loads based upon trophic transfer through diet and
      gill uptake for a Lake Erie food chain including two invasive species as a
      benthic-pelagic link. The model utilizes species-specific bioenergetic parameters
      in a four-level food chain including the green alga Scenedesmus quadricauda,
      zebra mussels (Dreissena polymorpha), round goby (Appollonia melanostoma), and
      the smallmouth bass (Micropterus dolomiu). The model was calibrated to current
      biotic concentrations and predicts an increase in contaminant load by almost 48%
      in the upper trophic level in two years. Validation to archival data resulted in
      <2% error from reported values following a two-year simulation. 

PMID- 26219071
TI  - Metal/metalloid elements and polycyclic aromatic hydrocarbon in various biochars:
      The effect of feedstock, temperature, minerals, and properties.
AB  - Fourteen metal/metalloid elements and sixteen polycyclic aromatic hydrocarbons
      (PAHs) within biochars were quantified to investigate how heat treatment
      temperatures (HTTs) and feedstocks affect their concentration and composition.
      Concentrations and composition of metals/metalloids were strongly dependent upon
      feedstocks rather than HTTs. HTTs significantly affected concentrations and
      composition of PAHs. The highest concentration of PAHs was observed for plant
      residue-derived biochars (PLABs) produced at 450  degrees C and the opposite
      result was for animal waste-derived bichars. High mineral content was responsible
      for depolymerization of organic matter (OM), which facilitated high production of
      PAHs. High HTTs pyrolysis or combustion PAHs (COMB) of PLABs possibly blocks
      their micropores derived from other components within OM and leads to a decline
      of CO2-surface areas (CO2-SAs). Concentration of ?COMB or individual PAH was
      affected by biochar properties, including composition and contents of functional
      groups, ash content, and CO2-SAs. PLABs produced at 600  degrees C were
      recommended for low toxicity. 

PMID- 26219072
TI  - Hexabromocyclododecane affects benthic-pelagic coupling in an experimental
      ecosystem.
AB  - Hexabromocyclododecane (HBCDD) is an additive brominated flame retardant and a
      recognized PBT chemical. However, little is known about its effects on coastal
      species, and even less on ecosystem effects. We investigated the dose-response
      effects of HBCDD over 8 months in 1000 L experimental mesocosms assembled from
      coastal Baltic Sea ecosystem components. HBCDD was added via spiked plankton
      material and a range of structural and functional endpoints were measured during
      the experiment. Increasing HBCDD concentration decreased the biomass of large
      Macoma balthica, resulting in a decreased recirculation of nutrients to the
      water. Changes in plankton communities were also observed, either due to direct
      toxic HBCDD effects or indirect via changes in benthic-pelagic coupling of
      nutrients. Such complex ecosystem responses can only be quantified and understood
      by using realistic experimental set-ups, and including knowledge of system
      specific ecological interactions. This is the first study of HBCDD effects on
      ecosystem level. 

PMID- 26219073
TI  - Biotransformation of arsenite and bacterial aox activity in drinking water
      produced from surface water of floating houses: Arsenic contamination in
      Cambodia.
AB  - The potential arsenite bioteansformation activity of arsenic was investigated by
      examining bacterial arsenic arsenite-oxidizing gene such as aoxS, aoxR, aoxA,
      aoxB, aoxC, and aoxD in high arsenic-contaminated drinking water produced from
      the surface water of floating houses. There is a biogeochemical cycle of activity
      involving arsenite oxidase aox system and the ars (arsenic resistance system)
      gene operon and aoxR leader gene activity in Alcaligenes faecalis SRR-11 and aoxS
      leader gene activity in Achromobacter xylosoxidans TSL-66. Batch experiments
      showed that SRR-11 and TSL-66 completely oxidized 1 mM of As (III) to As (V)
      within 35-40 h. The leaders of aoxS and aoxR are important for gene activity, and
      their effects in arsenic bioremediation and mobility in natural water has a
      significant ecological role because it allows arsenite oxidase in bacteria to
      control the biogeochemical cycle of arsenic-contaminated drinking water produced
      from surface water of floating houses. 

PMID- 26219074
TI  - Effects of atrazine on egg masses of the yellow-spotted salamander (Ambystoma
      maculatum) and its endosymbiotic alga (Oophila amblystomatis).
AB  - Embryonic growth of the yellow-spotted salamander (Ambystoma maculatum) is
      enhanced by the presence of the green alga Oophila amblystomatis, in the egg
      capsule. To further assess potential impacts of herbicides on this relationship,
      A. maculatum egg masses were exposed to atrazine (0-338 MUg/L) until hatching (up
      to 66 days). Exposure to atrazine reduced PSII yield of the symbiotic algae in a
      concentration-dependent manner, but did not significantly affect visible algal
      growth or any metrics associated with salamander development. Algal cells were
      also cultured in the laboratory for toxicity testing. In the 96-h growth
      inhibition test (0-680 MUg/L), ECx values were generally greater than those
      reported for standard algal test species. Complete recovery of growth rates
      occurred within 96-h of transferring cells to untreated media. Overall,
      development of A. maculatum embryos was not affected by exposure to atrazine at
      concentrations and durations exceeding those found in the environment. 

PMID- 26219075
TI  - The Moderately Efficient Enzyme: Futile Encounters and Enzyme Floppiness.
AB  - The pioneering model of Henri, Michaelis, and Menten was based on the fast
      equilibrium assumption: the substrate binds its enzyme reversibly, and substrate
      dissociation is much faster than product formation. Here, we examine this
      assumption from a somewhat different point of view, asking what fraction of
      enzyme-substrate complexes are futile, i.e., result in dissociation rather than
      product formation. In Knowles' notion of a "perfect" enzyme, all encounters of
      the enzyme with its substrate result in conversion to product. Thus, the perfect
      enzyme's catalytic efficiency, kcat/KM, is constrained by only the diffusion on
      rate, and the fraction of futile encounters (defined as phi) approaches zero. The
      available data on >1000 different enzymes suggest that for >=90% of enzymes phi >
      0.99 and for the "average enzyme" phi >= 0.9999; namely, <1 of 10(4) encounters
      is productive. Thus, the "fast equilibrium" assumption holds for the vast
      majority of enzymes. We discuss possible molecular origins for the dominance of
      futile encounters, including the coexistence of multiple sub-states of an
      enzyme's active site (enzyme floppiness) and/or its substrate. Floppiness relates
      to the inherent flexibility of proteins, but also to conflicting demands, or
      trade-offs, between rate acceleration (the rate-determining chemical step) and
      catalytic turnover, or between turnover rate and accuracy. The study of futile
      encounters and active-site floppiness may contribute to a better understanding of
      enzyme catalysis, enzyme evolution, and improved enzyme design. 

PMID- 26219076
TI  - Risk Factors for Contact Lens-Related Microbial Keratitis: A Case-Control
      Multicenter Study.
AB  - PURPOSE: The most feared complication of contact lens (CL) wear is microbial
      keratitis (MK), even though its incidence remains low. This study aimed to
      identify the risk factors of CL-related MK in a large, prospective, multicenter
      case-control study. METHODS: A multicenter case-control study was designed. The
      CL-related MK subpopulation (Case) was compared with healthy CL wearers (Control)
      using a 52-item anonymous questionnaire designed to determine subject
      demographics and lens wear history. Univariate and multivariate logistic
      regression analyses were performed to compare both groups. RESULTS: The study
      enrolled 499 cases and 508 controls. The risk factors associated with the
      greatest increased odds of CL-related MK were as follows: using disinfecting
      solution more than 3 months (odds ratio [OR]=1.94), cosmetic CL wear and use of
      multipurpose disinfection solution (1.37 each), overnight wear, and soft lens use
      (OR=1.24 each). The protective factors associated with the greatest reduction in
      OR were fitting by an ophthalmologist (OR=0.73) and hyperopia versus myopia
      (OR=0.75). CONCLUSIONS: The infectious determinants were linked to the type of
      lenses, hygiene routine, CL handling, disinfecting solution, and storage case.
      This study aimed to highlight the increasingly CL-related MK, which likely occurs
      because of lack of patient information regarding basic rules of hygiene and CL
      care and handling.

PMID- 26219077
TI  - Correlation of Handheld Infrared Skin Thermometer and Infrared Videothermography
      Device for Measurement of Corneal Temperature.
AB  - PURPOSE: In our study, we aimed to investigate the correlation of handheld
      infrared skin thermometer and videothermography device for the measurement of
      corneal temperature. METHODS: Forty healthy individuals (80 eyes) were enrolled
      to the study. Participants underwent a detailed ophthalmologic examination and
      medical history review for excluding any ocular and systemic diseases. The
      measurements of the central corneal temperature were performed in a room having
      constant temperature, humidity, and brightness levels. To avoid any variability,
      all the temperature measurements were performed in the same examination room by a
      single examiner. The temperature was measured with a handheld infrared skin
      thermometer (MEDISANA, FTN) from the corneal surface. The same instrument was
      also used to measure the subjects' body temperature. Moreover, the subjects
      underwent the corneal temperature measurement by a noncontact videothermography
      device (Optris PI 450; Optris GmbH). RESULTS: The male to female ratio was 19:21
      among the subjects. The mean age was 25.1+/-4.7 years. The mean body temperature
      was 36.93+/-0.33 degrees C. The mean corneal temperatures measured by the
      handheld infrared skin thermometer and the ocular videothermography device were
      36.94+/-0.28 degrees C and 35.61+/-0.61 degrees C, respectively (P<0.01). The
      mean temperature difference was 1.34+/-0.57 degrees C, with a 95% confidence
      interval. There was a moderate correlation between the corneal temperatures
      measured by the 2 devices in the right, the left eyes, and both eyes,
      respectively (P=0.450, 0.539, 0.490). CONCLUSIONS: Handheld infrared skin
      thermometers can be used for the evaluation of the corneal temperature. These
      devices may provide a simple, practical, and cheaper way to detect the corneal
      temperature, and the widely performed corneal temperature measurements may afford
      us to understand the temperature variability in numerous ocular conditions in a
      better way.

PMID- 26219078
TI  - Topographical and sex variations in the T2 relaxation times of articular
      cartilage in the ankle joints of healthy young adults using 3.0T MRI.
AB  - PURPOSE: To prospectively evaluate topographical and sex variations in the T2
      relaxation values of tibiotalar cartilage (TTC) of healthy young adults.
      MATERIALS AND METHODS: Sagittal 8-echo multiecho spin-echo T2 maps of TTC were
      acquired using a 3.0T MR in 25 male and 25 female healthy young adult
      participants. Quantitative measurements of T2 values in tibial cartilage (TBC)
      and talar cartilage (TLC) were obtained from three zones (anterior zone, AZ;
      middle zone, MZ; and posterior zone, PZ) and from four compartments (medial
      compartment, MC; midmedial compartment, MMC; midlateral compartment, MLC; and
      lateral compartment, LC) of TBC and TLC in the sagittal plane. RESULTS: The T2
      values of AZ (for TBC, 29.31 msec; for TLC, 35.81 msec) and MZ (for TBC, 28.56
      msec; for TLC, 36.12 msec) in males were significantly higher than those in
      females (for AZ of TBC, 26.99 msec; for AZ of TLC, 33.56 msec; for MZ of TBC,
      25.88 msec; for MZ of TLC, 31.85 msec) (for TBC, AZ, P = 0.009, MZ, P = 0.002;
      for TLC, AZ, P = 0.047, MZ, P = 0.001). Except for MMC and MLC of TBC (MMC, P =
      0.02, MLC, P = 0.03), TTC T2 values did not differ significantly between these
      compartment in either group (for TBC, MC, P = 0.27, LC, P = 0.37; for TLC, MC, P
      = 0.26, MMC, P = 0.08, MLC, P = 0.30, LC, P = 0.10). CONCLUSION: We found
      significant sex and topographic variations among TTC T2 values of healthy young
      adults. Acknowledgment of the significant topographical and sex variations in
      cartilage T2 values may minimize misinterpretation of ankle joint TTC T2 mapping
      data.

PMID- 26219079
TI  - Learning the Structure of Biomedical Relationships from Unstructured Text.
AB  - The published biomedical research literature encompasses most of our
      understanding of how drugs interact with gene products to produce physiological
      responses (phenotypes). Unfortunately, this information is distributed throughout
      the unstructured text of over 23 million articles. The creation of structured
      resources that catalog the relationships between drugs and genes would accelerate
      the translation of basic molecular knowledge into discoveries of genomic
      biomarkers for drug response and prediction of unexpected drug-drug interactions.
      Extracting these relationships from natural language sentences on such a large
      scale, however, requires text mining algorithms that can recognize when different
      looking statements are expressing similar ideas. Here we describe a novel
      algorithm, Ensemble Biclustering for Classification (EBC), that learns the
      structure of biomedical relationships automatically from text, overcoming
      differences in word choice and sentence structure. We validate EBC's performance
      against manually-curated sets of (1) pharmacogenomic relationships from PharmGKB
      and (2) drug-target relationships from DrugBank, and use it to discover new drug
      gene relationships for both knowledge bases. We then apply EBC to map the
      complete universe of drug-gene relationships based on their descriptions in
      Medline, revealing unexpected structure that challenges current notions about how
      these relationships are expressed in text. For instance, we learn that newer
      experimental findings are described in consistently different ways than
      established knowledge, and that seemingly pure classes of relationships can
      exhibit interesting chimeric structure. The EBC algorithm is flexible and
      adaptable to a wide range of problems in biomedical text mining. 

PMID- 26219080
TI  - End-of-Life Co-residence of Older Parents and Their Sons in Rural China.
AB  - This study examined how intergenerational exchanges with sons and daughters
      predicted older parents' likelihood of co-residing with a son prior to death in a
      rural area of China's Anhui Province. Our investigation drew on theories of
      contingent co-residence, modernization, and social exchange, conceptualizing co
      residence as having practical and symbolic importance in rural Chinese culture.
      The sample included 470 older parents, reported as deceased during 2001-2009, and
      their posthumous informants. We used logistic regression to assess
      intergenerational support and cohesion as predictors of co-residence with a son
      just prior to death. Older parents who provided instrumental support to, and
      received instrumental support from, sons and had better emotional relationships
      with sons were more likely than their counterparts to co-reside with a son at the
      end of life. Living with sons demonstrates filial piety for older parents at the
      end of life, but its realization is sensitive to intergenerational transactions.

PMID- 26219082
TI  - Ruminococcal cellulosomes: molecular Lego to deconstruct microcrystalline
      cellulose in human gut.

PMID- 26219083
TI  - Identification of the miRNA targetome in hippocampal neurons using RIP-seq.
AB  - MicroRNAs (miRNAs) are key players in the regulation of neuronal processes by
      targeting a large network of target messenger RNAs (mRNAs). However, the identity
      and function of mRNAs targeted by miRNAs in specific cells of the brain are
      largely unknown. Here, we established an adeno-associated viral vector (AAV)
      based neuron-specific Argonaute2:GFP-RNA immunoprecipitation followed by high
      throughput sequencing to analyse the regulatory role of miRNAs in mouse
      hippocampal neurons. Using this approach, we identified more than two thousand
      miRNA targets in hippocampal neurons, regulating essential neuronal features such
      as cell signalling, transcription and axon guidance. Furthermore, we found that
      stable inhibition of the highly expressed miR-124 and miR-125 in hippocampal
      neurons led to significant but distinct changes in the AGO2 binding of target
      mRNAs, resulting in subsequent upregulation of numerous miRNA target genes. These
      findings greatly enhance our understanding of the miRNA targetome in hippocampal
      neurons. 

PMID- 26219085
TI  - Engineering Transition-Metal-Coated Tungsten Carbides for Efficient and Selective
      Electrochemical Reduction of CO2 to Methane.
AB  - The design of catalysts for CO2 reduction is challenging because of the
      fundamental relationships between the binding energies of the reaction
      intermediates. Metal carbides have shown promise for transcending these
      relationships and enabling low-cost alternatives. Herein, we show that
      directional bonding arising from the mixed covalent/metallic character plays a
      critical role in governing the surface chemistry. This behavior can be described
      by consideration of individual d-band components. We use this model to predict
      efficient catalysts based on tungsten carbide with a sub-monolayer of iron
      adatoms. Our approach can be used to predict site-preference and binding-energy
      trends for complex catalyst surfaces. 

PMID- 26219086
TI  - Modular Design of Self-Assembling Peptide-Based Nanotubes.
AB  - An ability to design peptide-based nanotubes (PNTs) rationally with defined and
      mutable internal channels would advance understanding of peptide self-assembly,
      and present new biomaterials for nanotechnology and medicine. PNTs have been made
      from Fmoc dipeptides, cyclic peptides, and lock-washer helical bundles. Here we
      show that blunt-ended alpha-helical barrels, that is, preassembled bundles of
      alpha-helices with central channels, can be used as building blocks for PNTs.
      This approach is general and systematic, and uses a set of de novo helical
      bundles as standards. One of these bundles, a hexameric alpha-helical barrel,
      assembles into highly ordered PNTs, for which we have determined a structure by
      combining cryo-transmission electron microscopy, X-ray fiber diffraction, and
      model building. The structure reveals that the overall symmetry of the peptide
      module plays a critical role in ripening and ordering of the supramolecular
      assembly. PNTs based on pentameric, hexameric, and heptameric alpha-helical
      barrels sequester hydrophobic dye within their lumens. 

PMID- 26219084
TI  - Tooth matrix analysis for biomonitoring of organic chemical exposure: Current
      status, challenges, and opportunities.
AB  - Epidemiological evidence supports associations between prenatal exposure to
      environmental organic chemicals and childhood health impairments. Unlike the
      common choice of biological matrices such as urine and blood that can be limited
      by short half-lives for some chemicals, teeth provide a stable repository for
      chemicals with half-life in the order of decades. Given the potential of the
      tooth bio-matrix to study long-term exposures to environmental organic chemicals
      in human biomonitoring programs, it is important to be aware of possible pitfalls
      and potential opportunities to improve on the current analytical method for tooth
      organics analysis. We critically review previous results of studies of this
      topic. The major drawbacks and challenges in currently practiced concepts and
      analytical methods in utilizing tooth bio-matrix are (i) no consideration of
      external (from outer surface) or internal contamination (from micro-odontoblast
      processes), (ii) the misleading assumption that whole ground teeth represent
      prenatal exposures (latest formed dentine is lipid rich and therefore would
      absorb and accumulate more organic chemicals), (iii) reverse causality in
      exposure assessment due to whole ground teeth, and (iv) teeth are a precious bio
      matrix and grinding them raises ethical concerns about appropriate use of a very
      limited resource in exposure biology and epidemiology studies. These can be
      overcome by addressing the important limitations and possible improvements with
      the analytical approach associated at each of the following steps: (i) tooth
      sample preparation to retain exposure timing, (ii) organics extraction and pre
      concentration to detect ultra-trace levels of analytes, (iii) chromatography
      separation, (iv) mass spectrometric detection to detect multi-class organics
      simultaneously, and (v) method validation, especially to exclude chance findings.
      To highlight the proposed improvements we present findings from a pilot study
      that utilizes tooth matrix biomarkers to obtain trimester-specific exposure
      information for a range of organic chemicals. 

PMID- 26219088
TI  - Back to work? Socioeconomic status after kidney transplantation.
AB  - PRINCIPLES: Employment after kidney transplantation is an important marker of
      health recovery. The study addresses the impact of successful kidney
      transplantation on socioeconomic factors and employment in a Swiss cohort.
      METHODS: Patients who received a kidney allograft at the University Hospital of
      Basel between 2000 and 2011 were investigated. A standardised survey was used to
      obtain information on socioeconomic factors 1 year before and after successful
      transplantation. RESULTS: A total of 610 patients were contacted; 354 (58%)
      answered the survey. The median age of respondents was 53.5 (interquartile range
      42-61) years at the time of transplantation, 31.2% were females. Overall, 201 out
      of 282 working-age patients (71.3%) were working 1 year after transplantation:
      102 full-time, 55 part-time, 30 patients part-time with additional disability
      pension, and 14 housework. Seventy-two patients (25.3%) did not work 1 year after
      transplantation: 63 patients had a full or partial disability pension, and nine
      patients were unemployed. Thirty out of 282 working-age patients (10.6%) had
      improved working ability after transplantation. Employment after transplantation
      was favoured by: living donor transplantation (p <0.0001), pre-emptive
      transplantation (p <0.0001), dialysis duration <=1 year (p <0.0001), preserved
      employment before transplantation (p <0.0001), and higher education (p = 0.003),
      whereas age above 50 years (p = 0.006), and dialysis duration > 1 year (p
      <0.0001) had a negative impact. CONCLUSION: The employment rate in this Swiss
      cohort before and after successful kidney transplantation is high compared with
      the literature. A high number of living donors, of pre-emptive transplantations,
      and short dialysis vintages contribute to this observation.

PMID- 26219089
TI  - Why have fatality rates among older drivers declined? The relative contributions
      of changes in survivability and crash involvement.
AB  - OBJECTIVES: This study examined the trend in fatality rates per vehicle miles
      traveled (VMT) among older drivers relative to middle-aged drivers and quantified
      the contributions of changes in crash involvement and survivability to this
      trend. METHODS: Using U.S. national databases, changes in driver deaths per crash
      involvement (marker of death risk when involved in a crash) and crash
      involvements per VMT (marker of crash risk) from 1995-1998 to 2005-2008 among
      older drivers aged 70 and over relative to changes among middle-aged drivers aged
      35-54 were computed. The contributions of these components to the relative
      changes in older drivers' fatality rates per VMT were calculated using the
      decomposition methodology. RESULTS: Fatality rates per VMT declined more among
      older drivers than among middle-aged drivers over the study period. Relative to
      middle-aged drivers, drivers aged 75 and older experienced large declines in
      crash risk and modest declines in death risk. Relative declines in crash risk
      accounted for 68-74% of the larger decline in fatalities per VMT among drivers
      aged 75 and older compared with middle-aged drivers. Drivers aged 70-74
      experienced modest relative declines in crash risk and death risk. Declines in
      death risk among drivers aged 75 and older relative to middle-aged drivers were
      much larger in side-impact crashes; improvements in crash survivability accounted
      for nearly half of the relative decline in fatality rates in these crashes.
      Relative survivability did not change significantly in frontal impacts. Higher
      death risk was more important than higher crash risk in explaining older drivers'
      elevated fatality rates per VMT relative to middle-aged drivers during 1995-1998,
      and the contribution of heightened death risk was even greater during 2005-2008.
      CONCLUSIONS: Many factors may have reduced crash involvements among drivers 75
      and older, including changes in travel patterns, health, and roadway design. In
      side impacts, side airbags and reduced passenger vehicle incompatibility may have
      improved survivability for older drivers. Because excess fragility now makes an
      even larger contribution to older drivers' elevated fatality rates, future
      countermeasures that improve survivability can likely provide large benefits.

PMID- 26219087
TI  - Human xylosyltransferases--mediators of arthrofibrosis? New pathomechanistic
      insights into arthrofibrotic remodeling after knee replacement therapy.
AB  - Total knee replacement (TKR) is a common therapeutic option to restore joint
      functionality in chronic inflammatory joint diseases. Subsequent arthrofibrotic
      remodeling occurs in 10%, but the underlying pathomechanisms remain unclear. We
      evaluated the association of xylosyltransferases (XT), fibrotic mediators
      catalyzing glycosaminoglycan biosynthesis, leading to arthrofibrosis as well as
      the feasibility of using serum XT activity as a diagnostic marker. For this
      purpose, synovial fibroblasts (SF) were isolated from arthrofibrotic and control
      synovial biopsies. Basal alpha-smooth muscle actin expression revealed a high
      fibroblast-myofibroblast transition rate in arthrofibrotic fibroblasts. Fibrotic
      remodeling marked by enhanced XT activity, alpha-SMA protein expression as well
      as xylosyltransferase-I, collagen type III-alpha-1 and ACTA2 mRNA expression was
      stronger in arthrofibrotic than in control fibroblasts treated with transforming
      growth factor-beta1 (TGF-beta1). Otherwise, no differences between serum levels
      of XT-I activity or common fibrosis markers (galectin-3 and growth
      differentiation factor-15 levels (GDF-15)) were found between 95 patients with
      arthrofibrosis and 132 controls after TKR. In summary, XT-I was initially
      investigated as a key cellular mediator of arthrofibrosis and a target for
      therapeutic intervention. However, the blood-synovial-barrier makes
      arthrofibrotic molecular changes undetectable in serum. Future studies on
      monitoring or preventing arthrofibrotic remodeling should therefore rely on local
      instead of systemic parameters. 

PMID- 26219090
TI  - The Promise of Effective Pain Treatment Outcomes: Rallying Academic Centers to
      Lead the Charge.

PMID- 26219091
TI  - Potential force dynamics of heart rate variability reflect cardiac autonomic
      modulation with respect to posture, age, and breathing pattern.
AB  - RATIONALE: Various physiological and pathological conditions are correlated with
      cardiac autonomic function. Heart rate variability is a marker of cardiac
      autonomic modulation and can be measured by several methods. However, the
      available methods are sensitive to breathing patterns. OBJECTIVES: To quantify
      cardiac autonomic modulation by observing the potential force dynamics of the R-R
      interval time series in healthy individuals. METHODS: We propose two "potentials
      of unbalanced complex kinetic" (PUCK) parameters to quantify the characteristics
      of the potential force dynamics of R-R interval time series: potential strength
      (slope) and fluctuation size (slope standard deviations [SSD1, SSD2]). We applied
      this method to the series of R-R intervals obtained from 30 healthy subjects in
      an experimental condition that elicited cardiac autonomic (i.e., sympathetic and
      vagal) activation (in supine, sitting, and standing positions). Subjects were
      categorized into three groups by decade (i.e., 20 s, 30 s, and 40 s) to verify
      the cardiac autonomic differences by age. Two respiration patterns were
      introduced to check the influence of the pattern into the analytical results.
      MEASUREMENTS AND MAIN RESULTS: Sympathetic modulation activation significantly
      increased the slope and reduced SSD1 and SSD2; these trends were confirmed in all
      groups. The slope is concordant with the result of the low frequency/high
      frequency (LF/HF) ratio in frequency components as an indicator of sympathetic
      modulation. No trend was observed in slope among age groups. However, SSD1 and
      SSD2 in the 40 s group were significantly decreased in the supine and sitting
      positions. The results with respect to respiration frequency showed lower
      sympathetic modulation as shown in the LF/HF ratio and slope, whereas higher
      vagal modulation as shown in the HF appeared with a longer breathing rate.
      CONCLUSIONS: PUCK can quantify the cardiac autonomic modulation in the
      experimental conditions of different postures. SSD1 and SSD2 are more sensitive
      to age than frequency components and are unaffected by breathing patterns. This
      method may be an alternative method for observing cardiac autonomic modulation in
      clinical practice.

PMID- 26219093
TI  - Tone-Replacement Error Diffusion for Multitoning.
AB  - Error diffusion is an efficient halftone method for mainly being applied on
      printers. The promising high image quality and processing efficiency endorse it
      as a popular and competitive candidate in halftoning and multitoning
      applications. The multitoning is an extension of halftoning, adopting more than
      two-tone levels for the improvement of the similarity between an original image
      and the converted image. Yet, the banding effect, indicating the areas with
      discontinuous tone level, disturbs the visual perception, and thus seriously
      degrades image quality. To solve the banding effect, the tone-replacement
      strategy is proposed in this paper. As documented in the experimental results,
      excellent tone-similarity as that of the original image and promising
      reconstructed dot-distribution can be provided simultaneously. Comparing with the
      former banding-free methods, the apparent improvements/features suggest that the
      proposed method can be a very competitive candidate for multitoning applications.

PMID- 26219092
TI  - Rational Design of a Hierarchical Tin Dendrite Electrode for Efficient
      Electrochemical Reduction of CO2.
AB  - Catalysis is a key technology for the synthesis of renewable fuels through
      electrochemical reduction of CO2 . However, successful CO2 reduction still
      suffers from the lack of affordable catalyst design and understanding the factors
      governing catalysis. Herein, we demonstrate that the CO2 conversion selectivity
      on Sn (or SnOx /Sn) electrodes is correlated to the native oxygen content at the
      subsurface. Electrochemical analyses show that the reduced Sn electrode with
      abundant oxygen species effectively stabilizes a CO2 (.-) intermediate rather
      than the clean Sn surface, and consequently results in enhanced formate
      production in the CO2 reduction. Based on this design strategy, a hierarchical Sn
      dendrite electrode with high oxygen content, consisting of a multi-branched
      conifer-like structure with an enlarged surface area, was synthesized. The
      electrode exhibits a superior formate production rate (228.6 MUmol h(-1)  cm(-2)
      ) at -1.36 VRHE without any considerable catalytic degradation over 18 h of
      operation. 

PMID- 26219094
TI  - Mitosis Detection for Invasive Breast Cancer Grading in Histopathological Images.
AB  - Histopathological grading of cancer not only offers an insight to the patients'
      prognosis but also helps in making individual treatment plans. Mitosis counts in
      histopathological slides play a crucial role for invasive breast cancer grading
      using the Nottingham grading system. Pathologists perform this grading by manual
      examinations of a few thousand images for each patient. Hence, finding the
      mitotic figures from these images is a tedious job and also prone to observer
      variability due to variations in the appearances of the mitotic cells. We propose
      a fast and accurate approach for automatic mitosis detection from
      histopathological images. We employ area morphological scale space for cell
      segmentation. The scale space is constructed in a novel manner by restricting the
      scales with the maximization of relative-entropy between the cells and the
      background. This results in precise cell segmentation. The segmented cells are
      classified in mitotic and non-mitotic category using the random forest
      classifier. Experiments show at least 12% improvement in F1 score on more than
      450 histopathological images at 40* magnification. 

PMID- 26219095
TI  - Markov Network-Based Unified Classifier for Face Recognition.
AB  - In this paper, we propose a novel unifying framework using a Markov network to
      learn the relationships among multiple classifiers. In face recognition, we
      assume that we have several complementary classifiers available, and assign
      observation nodes to the features of a query image and hidden nodes to those of
      gallery images. Under the Markov assumption, we connect each hidden node to its
      corresponding observation node and the hidden nodes of neighboring classifiers.
      For each observation-hidden node pair, we collect the set of gallery candidates
      most similar to the observation instance, and capture the relationship between
      the hidden nodes in terms of a similarity matrix among the retrieved gallery
      images. Posterior probabilities in the hidden nodes are computed using the belief
      propagation algorithm, and we use marginal probability as the new similarity
      value of the classifier. The novelty of our proposed framework lies in the method
      that considers classifier dependence using the results of each neighboring
      classifier. We present the extensive evaluation results for two different
      protocols, known and unknown image variation tests, using four publicly available
      databases: 1) the Face Recognition Grand Challenge ver. 2.0; 2) XM2VTS; 3) BANCA;
      and 4) Multi-PIE. The result shows that our framework consistently yields
      improved recognition rates in various situations. 

PMID- 26219096
TI  - Robust Ellipse Fitting via Half-Quadratic and Semidefinite Relaxation
      Optimization.
AB  - Ellipse fitting is widely applied in the fields of computer vision and automatic
      manufacture. However, the introduced edge point errors (especially outliers) from
      image edge detection will cause severe performance degradation of the subsequent
      ellipse fitting procedure. To alleviate the influence of outliers, we develop a
      robust ellipse fitting method in this paper. The main contributions of this paper
      are as follows. First, to be robust against the outliers, we introduce the
      maximum correntropy criterion into the constrained least-square (CLS) ellipse
      fitting method, and apply the half-quadratic optimization algorithm to solve the
      nonlinear and nonconvex problem in an alternate manner. Second, to ensure that
      the obtained solution is related to an ellipse, we introduce a special quadratic
      equality constraint into the aforementioned CLS model, which results in the
      nonconvex quadratically constrained quadratic programming problem. Finally, we
      derive the semidefinite relaxation version of the aforementioned problem in terms
      of the trace operator and thus determine the ellipse parameters using
      semidefinite programming. Some simulated and experimental examples are presented
      to illustrate the effectiveness of the proposed ellipse fitting approach. 

PMID- 26219097
TI  - Visual Orientation Selectivity Based Structure Description.
AB  - The human visual system is highly adaptive to extract structure information for
      scene perception, and structure character is widely used in perception-oriented
      image processing works. However, the existing structure descriptors mainly
      describe the luminance contrast of a local region, but cannot effectively
      represent the spatial correlation of structure. In this paper, we introduce a
      novel structure descriptor according to the orientation selectivity mechanism in
      the primary visual cortex. Research on cognitive neuroscience indicate that the
      arrangement of excitatory and inhibitory cortex cells arise orientation
      selectivity in a local receptive field, within which the primary visual cortex
      performs visual information extraction for scene understanding. Inspired by the
      orientation selectivity mechanism, we compute the correlations among pixels in a
      local region based on the similarities of their preferred orientation. By
      imitating the arrangement of the excitatory/inhibitory cells, the correlations
      between a central pixel and its local neighbors are binarized, and the spatial
      correlation is represented with a set of binary values, which is named the
      orientation selectivity-based pattern. Then, taking both the gradient magnitude
      and the orientation selectivity-based pattern into account, a rotation invariant
      structure descriptor is introduced. The proposed structure descriptor is applied
      in texture classification and reduced reference image quality assessment, as two
      different application domains to verify its generality and robustness.
      Experimental results demonstrate that the orientation selectivity-based structure
      descriptor is robust to disturbance, and can effectively represent the structure
      degradation caused by different types of distortion. 

PMID- 26219098
TI  - Telerobotic Haptic Exploration in Art Galleries and Museums for Individuals with
      Visual Impairments.
AB  - This paper presents a haptic telepresence system that enables visually impaired
      users to explore locations with rich visual observation such as art galleries and
      museums by using a telepresence robot, a RGB-D sensor (color and depth camera),
      and a haptic interface. The recent improvement on RGB-D sensors has enabled real
      time access to 3D spatial information in the form of point clouds. However, the
      real-time representation of this data in the form of tangible haptic experience
      has not been challenged enough, especially in the case of telepresence for
      individuals with visual impairments. Thus, the proposed system addresses the real
      time haptic exploration of remote 3D information through video encoding and real
      time 3D haptic rendering of the remote real-world environment. This paper
      investigates two scenarios in haptic telepresence, i.e., mobile navigation and
      object exploration in a remote environment. Participants with and without visual
      impairments participated in our experiments based on the two scenarios, and the
      system performance was validated. In conclusion, the proposed framework provides
      a new methodology of haptic telepresence for individuals with visual impairments
      by providing an enhanced interactive experience where they can remotely access
      public places (art galleries and museums) with the aid of haptic modality and
      robotic telepresence. 

PMID- 26219099
TI  - Adaptive Robust Online Constructive Fuzzy Control of a Complex Surface Vehicle
      System.
AB  - In this paper, a novel adaptive robust online constructive fuzzy control (AR
      OCFC) scheme, employing an online constructive fuzzy approximator (OCFA), to deal
      with tracking surface vehicles with uncertainties and unknown disturbances is
      proposed. Significant contributions of this paper are as follows: 1) unlike
      previous self-organizing fuzzy neural networks, the OCFA employs decoupled
      distance measure to dynamically allocate discriminable and sparse fuzzy sets in
      each dimension and is able to parsimoniously self-construct high interpretable T
      S fuzzy rules; 2) an OCFA-based dominant adaptive controller (DAC) is designed by
      employing the improved projection-based adaptive laws derived from the Lyapunov
      synthesis which can guarantee reasonable fuzzy partitions; 3) closed-loop system
      stability and robustness are ensured by stable cancelation and decoupled adaptive
      compensation, respectively, thereby contributing to an auxiliary robust
      controller (ARC); and 4) global asymptotic closed-loop system can be guaranteed
      by AR-OCFC consisting of DAC and ARC and all signals are bounded. Simulation
      studies and comprehensive comparisons with state-of-the-arts fixed- and dynamic
      structure adaptive control schemes demonstrate superior performance of the AR
      OCFC in terms of tracking and approximation accuracy.

PMID- 26219100
TI  - Crowd Event Detection on Optical Flow Manifolds.
AB  - Analyzing crowd events in a video is key to understanding the behavioral
      characteristics of people (humans). Detecting crowd events in videos is
      challenging because of articulated human movements and occlusions. The aim of
      this paper is to detect the events in a probabilistic framework for automatically
      interpreting the visual crowd behavior. In this paper, crowd event detection and
      classification in optical flow manifolds (OFMs) are addressed. A new algorithm to
      detect walking and running events has been proposed, which uses optical flow
      vector lengths in OFMs. Furthermore, a new algorithm to detect merging and
      splitting events has been proposed, which uses Riemannian connections in the
      optical flow bundle (OFB). The longest vector from the OFB provides a key feature
      for distinguishing walking and running events. Using a Riemannian connection, the
      optical flow vectors are parallel transported to localize the crowd groups. The
      geodesic lengths among the groups provide a criterion for merging and splitting
      events. Dispersion and evacuation events are jointly modeled from the
      walking/running and merging/splitting events. Our results show that the proposed
      approach delivers a comparable model to detect crowd events. Using the
      performance evaluation of tracking and surveillance 2009 dataset, the proposed
      method is shown to produce the best results in merging, splitting, and dispersion
      events, and comparable results in walking, running, and evacuation events when
      compared with other methods.

PMID- 26219101
TI  - Dynamic Neural Networks for Kinematic Redundancy Resolution of Parallel Stewart
      Platforms.
AB  - Redundancy resolution is a critical problem in the control of parallel Stewart
      platform. The redundancy endows us with extra design degree to improve system
      performance. In this paper, the kinematic control problem of Stewart platforms is
      formulated to a constrained quadratic programming. The Karush-Kuhn-Tucker
      conditions of the problem is obtained by considering the problem in its dual
      space, and then a dynamic neural network is designed to solve the optimization
      problem recurrently. Theoretical analysis reveals the global convergence of the
      employed dynamic neural network to the optimal solution in terms of the defined
      criteria. Simulation results verify the effectiveness in the tracking control of
      the Stewart platform for dynamic motions.

PMID- 26219102
TI  - Multiple Trigger Points for Quantifying Heat-Health Impacts: New Evidence from a
      Hot Climate.
AB  - BACKGROUND: Extreme heat is a public health challenge. The scarcity of directly
      comparable studies on the association of heat with morbidity and mortality and
      the inconsistent identification of threshold temperatures for severe impacts
      hampers the development of comprehensive strategies aimed at reducing adverse
      heat-health events. OBJECTIVES: This quantitative study was designed to link
      temperature with mortality and morbidity events in Maricopa County, Arizona, USA,
      with a focus on the summer season. METHODS: Using Poisson regression models that
      controlled for temporal confounders, we assessed daily temperature-health
      associations for a suite of mortality and morbidity events, diagnoses, and
      temperature metrics. Minimum risk temperatures, increasing risk temperatures, and
      excess risk temperatures were statistically identified to represent different
      "trigger points" at which heat-health intervention measures might be activated.
      RESULTS: We found significant and consistent associations of high environmental
      temperature with all-cause mortality, cardiovascular mortality, heat-related
      mortality, and mortality resulting from conditions that are consequences of heat
      and dehydration. Hospitalizations and emergency department visits due to heat
      related conditions and conditions associated with consequences of heat and
      dehydration were also strongly associated with high temperatures, and there were
      several times more of those events than there were deaths. For each temperature
      metric, we observed large contrasts in trigger points (up to 22  degrees C)
      across multiple health events and diagnoses. CONCLUSION: Consideration of
      multiple health events and diagnoses together with a comprehensive approach to
      identifying threshold temperatures revealed large differences in trigger points
      for possible interventions related to heat. Providing an array of heat trigger
      points applicable for different end-users may improve the public health response
      to a problem that is projected to worsen in the coming decades.

PMID- 26219105
TI  - Creatine and Caffeine: Considerations for Concurrent Supplementation.
AB  - Nutritional supplementation is a common practice among athletes, with creatine
      and caffeine among the most commonly used ergogenic aids. Hundreds of studies
      have investigated the ergogenic potential of creatine supplementation, with
      consistent improvements in strength and power reported for exercise bouts of
      short duration (<= 30 s) and high intensity. Caffeine has been shown to improve
      endurance exercise performance, but results are mixed in the context of strength
      and sprint performance. Further, there is conflicting evidence from studies
      comparing the ergogenic effects of coffee and caffeine anhydrous supplementation.
      Previous research has identified independent mechanisms by which creatine and
      caffeine may improve strength and sprint performance, leading to the formulation
      of multi-ingredient supplements containing both ingredients. Although scarce,
      research has suggested that caffeine ingestion may blunt the ergogenic effect of
      creatine. While a pharmacokinetic interaction is unlikely, authors have suggested
      that this effect may be explained by opposing effects on muscle relaxation time
      or gastrointestinal side effects from simultaneous consumption. The current
      review aims to evaluate the ergogenic potential of creatine and caffeine in the
      context of high-intensity exercise. Research directly comparing coffee and
      caffeine anhydrous is discussed, along with previous studies evaluating the
      concurrent supplementation of creatine and caffeine.

PMID- 26219104
TI  - Environmental Chemicals in Urine and Blood: Improving Methods for Creatinine and
      Lipid Adjustment.
AB  - BACKGROUND: Investigators measuring exposure biomarkers in urine typically adjust
      for creatinine to account for dilution-dependent sample variation in urine
      concentrations. Similarly, it is standard to adjust for serum lipids when
      measuring lipophilic chemicals in serum. However, there is controversy regarding
      the best approach, and existing methods may not effectively correct for
      measurement error. OBJECTIVES: We compared adjustment methods, including novel
      approaches, using simulated case-control data. METHODS: Using a directed acyclic
      graph framework, we defined six causal scenarios for epidemiologic studies of
      environmental chemicals measured in urine or serum. The scenarios include
      variables known to influence creatinine (e.g., age and hydration) or serum lipid
      levels (e.g., body mass index and recent fat intake). Over a range of true effect
      sizes, we analyzed each scenario using seven adjustment approaches and estimated
      the corresponding bias and confidence interval coverage across 1,000 simulated
      studies. RESULTS: For urinary biomarker measurements, our novel method, which
      incorporates both covariate-adjusted standardization and the inclusion of
      creatinine as a covariate in the regression model, had low bias and possessed 95%
      confidence interval coverage of nearly 95% for most simulated scenarios. For
      serum biomarker measurements, a similar approach involving standardization plus
      serum lipid level adjustment generally performed well. CONCLUSIONS: To control
      measurement error bias caused by variations in serum lipids or by urinary
      diluteness, we recommend improved methods for standardizing exposure
      concentrations across individuals.

PMID- 26219103
TI  - Desert Dust Outbreaks in Southern Europe: Contribution to Daily PM10
      Concentrations and Short-Term Associations with Mortality and Hospital
      Admissions.
AB  - BACKGROUND: Evidence on the association between short-term exposure to desert
      dust and health outcomes is controversial. OBJECTIVES: We aimed to estimate the
      short-term effects of particulate matter <= 10 MUm (PM10) on mortality and
      hospital admissions in 13 Southern European cities, distinguishing between PM10
      originating from the desert and from other sources. METHODS: We identified desert
      dust advection days in multiple Mediterranean areas for 2001-2010 by combining
      modeling tools, back-trajectories, and satellite data. For each advection day, we
      estimated PM10 concentrations originating from desert, and computed PM10 from
      other sources by difference. We fitted city-specific Poisson regression models to
      estimate the association between PM from different sources (desert and non
      desert) and daily mortality and emergency hospitalizations. Finally, we pooled
      city-specific results in a random-effects meta-analysis. RESULTS: On average, 15%
      of days were affected by desert dust at ground level (desert PM10 > 0 MUg/m3).
      Most episodes occurred in spring-summer, with increasing gradient of both
      frequency and intensity north-south and west-east of the Mediterranean basin. We
      found significant associations of both PM10 concentrations with mortality.
      Increases of 10 MUg/m3 in non-desert and desert PM10 (lag 0-1 days) were
      associated with increases in natural mortality of 0.55% (95% CI: 0.24, 0.87%) and
      0.65% (95% CI: 0.24, 1.06%), respectively. Similar associations were estimated
      for cardio-respiratory mortality and hospital admissions. CONCLUSIONS: PM10
      originating from the desert was positively associated with mortality and
      hospitalizations in Southern Europe. Policy measures should aim at reducing
      population exposure to anthropogenic airborne particles even in areas with large
      contribution from desert dust advections. CITATION: Stafoggia M, Zauli-Sajani S,
      Pey J, Samoli E, Alessandrini E, Basagana X, Cernigliaro A, Chiusolo M, Demaria
      M, Diaz J, Faustini A, Katsouyanni K, Kelessis AG, Linares C, Marchesi S, Medina
      S, Pandolfi P, Perez N, Querol X, Randi G, Ranzi A, Tobias A, Forastiere F, MED
      PARTICLES Study Group. 2016. Desert dust outbreaks in Southern Europe:
      contribution to daily PM10 concentrations and short-term associations with
      mortality and hospital admissions. Environ Health Perspect 124:413-419;
      http://dx.doi.org/10.1289/ehp.1409164.

PMID- 26219106
TI  - The Effect of Different Repeated-High-Intensity-Effort Bouts on Subsequent
      Running, Skill Performance, and Neuromuscular Function.
AB  - PURPOSE: To assess the impact of different repeated-high-intensity-effort (RHIE)
      bouts on player activity profiles, skill involvements, and neuromuscular fatigue
      during small-sided games. PARTICIPANTS: 22 semiprofessional rugby league players
      (age 24.0 +/- 1.8 y, body mass 95.6 +/- 7.4 kg). METHODS: During 4 testing
      sessions, they performed RHIE bouts that each differed in the combination of
      contact and running efforts, followed by a 5-min off-side small-sided game before
      performing a second bout of RHIE activity and another 5-min small-sided game.
      Global positioning system microtechnology and video recordings provided
      information on activity profiles and skill involvements. A countermovement jump
      and a plyometric push-up assessed changes in lower- and upper-body neuromuscular
      function after each session. RESULTS: After running-dominant RHIE bouts, players
      maintained running intensities during both games. In the contact-dominant RHIE
      bouts, reductions in moderate-speed activity were observed from game 1 to game 2
      (ES = -0.71 to -1.06). There was also moderately lower disposal efficiency across
      both games after contact-dominant RHIE activity compared with running-dominant
      activity (ES = 0.62-1.02). Greater reductions in lower-body fatigue occurred as
      RHIE bouts became more running dominant (ES = -0.01 to -1.36), whereas upper-body
      fatigue increased as RHIE bouts became more contact dominant (ES = -0.07 to 
      1.55). CONCLUSIONS: Physical contact causes reductions in running intensity and
      the quality of skill involvements during game-based activities. In addition, the
      neuromuscular fatigue experienced by players is specific to the activities
      performed.

PMID- 26219107
TI  - [The Protective Role of Endoscopic Sphincterotomy and/or Cholecystectomy for
      Recurrence of Acute Biliary Pancreatitis].

PMID- 26219108
TI  - [Rapidly Growing Interval Colon Cancer].

PMID- 26219109
TI  - [What Is the Long-term Effect of Helicobacter pylori Eradication on  Gastric
      Adenoma?].

PMID- 26219110
TI  - Evidence appraisal of  Arrowsmith VA, Taylor R. Removal of nail polish  and
      finger rings to prevent surgical infection  (Review). Cochrane Database Syst Rev.
      2014;8:CD003325.
AB  - This systematic review revealed that there remains no evidence to indicate
      whether removing nail polish and finger rings affects the rate of SSIs after
      surgery. Given that there are no new studies on this topic, there is insufficient
      evidence to determine whether wearing finger rings or nail polish affects the
      number of bacteria on the skin after surgical hand scrubbing.

PMID- 26219111
TI  - A reminder about the importance of the   time out.

PMID- 26219112
TI  - Improving team engagement during the   time out.

PMID- 26219113
TI  - What's new in SSI prevention?

PMID- 26219114
TI  - Sponge-hydrostatic and weeping bearings.

PMID- 26219115
TI  - Americans' Experiences with Marketplace and Medicaid Coverage. Findings from the
      Commonwealth Fund Affordable Care Act Tracking Survey, March-May 2015.
AB  - The latest Commonwealth Fund Affordable Care Act Tracking Survey finds the share
      of uninsured working-age adults was 13 percent in March-May 2015, compared with
      20 percent just before the major coverage expansions went into effect. More than
      half of adults who currently have coverage either through the Affordable Care
      Act's (ACA's) marketplace plans or Medicaid expansion were uninsured prior to
      gaining coverage. Of those, more than 60 percent lacked coverage for one year or
      longer. More than six of 10 adults who used their new plans to obtain care
      reported they could not have afforded or accessed it previously. Majorities of
      people with ACA coverage who have used their plans express satisfaction with the
      doctors covered in their networks and are able to find physicians with relative
      ease. Wait times to get appointments with physicians in marketplace plans and
      Medicaid are comparable to those reported by other working-age adults.

PMID- 26219116
TI  - Modernizing Medicare's Benefit Design and Low-Income Subsidies to Ensure Access
      and Affordability.
AB  - Insurance coverage through the traditional Medicare program is complex,
      fragmented, and incomplete. Beneficiaries must purchase supplemental private
      insurance to fill in the gaps. While impoverished beneficiaries may receive
      supplemental coverage through Medicaid and subsidies for prescription drugs, help
      is limited for people with incomes above the poverty level. This patchwork quilt
      leads to confusion for beneficiaries and high administrative costs, while also
      undermining coverage and care coordination. Most important, Medicare's benefits
      fail to limit out-of-pocket costs or ensure adequate financial protection,
      especially for beneficiaries with low incomes and serious health problems. This
      brief, part of a series about Medicare's past, present, and future, presents
      options for an integrated benefit for enrollees in traditional Medicare. The new
      benefit would not only reduce cost burdens but also could potentially strengthen
      the Medicare program and enhance its role in stimulating and supporting
      innovations throughout the health care delivery system.

PMID- 26219117
TI  - Predictable Unpredictability: the Problem with Basing Medicare Policy on Long
      Term Financial Forecasting.
AB  - The authors assess how Medicare financing and projections of future costs have
      changed since 2000. They also assess the impact of legislative reforms on the
      sources and levels of financing and compare cost forecasts made at different
      times. Although the aging U.S. population and rising health care costs are
      expected to increase the share of gross domestic product devoted to Medicare,
      changes made in the program over the past decade have helped stabilize Medicare's
      financial outlook--even as benefits have been expanded. Long-term forecasting
      uncertainty should make policymakers and beneficiaries wary of dramatic changes
      to the program in the near term that are intended to alter its long-term
      forecast: the range of error associated with cost forecasts rises as the forecast
      window lengthens. Instead, policymakers should focus on the immediate policy
      window, taking steps to reduce the current burden of Medicare costs by containing
      spending today.

PMID- 26219118
TI  - Serving Older Adults with Complex Care Needs: A New Benefit Option for Medicare.
AB  - Medicare was originally designed to protect beneficiaries from the financial
      burden of acute episodes of illness. As lifespans lengthen, Medicare must adapt
      to serve beneficiaries with substantial long-term physical or cognitive
      impairment who need personal care assistance. These beneficiaries often incur
      high out-of-pocket costs for Medicare-covered services as well as home and
      community care not covered by Medicare. This latter category of care is often key
      to continued independence. To improve Medicare's capacity to serve such
      beneficiaries, and to prevent unnecessary institutionalization, this issue brief,
      one in a series on Medicare's future challenges, proposes a complex care benefit
      option that would include home and community services, and describes how it might
      be structured to balance the goals of improving care for beneficiaries and
      ensuring affordability.

PMID- 26219119
TI  - Closing the Gap: Past Performance of Health Insurance in Reducing Racial and
      Ethnic Disparities in Access to Care Could Be an Indication of Future Results.
AB  - This historical analysis shows that in the years just prior to the Affordable
      Care Act's expansion of health insurance coverage, black and Hispanic working-age
      adults were far more likely than whites to be uninsured, to lack a usual care
      provider, and to go without needed care because of cost. Among insured adults
      across all racial and ethnic groups, however, rates of access to a usual provider
      were much higher, and the proportion of adults going without needed care because
      of cost was much lower. Disparities between groups were narrower among the
      insured than the uninsured, even after adjusting for income, age, sex, and health
      status. With surveys pointing to a decline in uninsured rates among black and
      Hispanic adults in the past year, particularly in states extending Medicaid
      eligibility, the ACA's coverage expansions have the potential to reduce, though
      not eliminate, racial and ethnic disparities in access to care.

PMID- 26219120
TI  - [Guidelines for the prevention, diagnosis and treatment of acute kidney injury
      syndromes: Italian version of KDIGO, integrated with new evidence and
      international commentaries].

PMID- 26219122
TI  - Lifestyle modifications help reduce stroke risk.

PMID- 26219121
TI  - Does the nose know your future health?

PMID- 26219123
TI  - New recommendations about kidney stones.

PMID- 26219124
TI  - New year, new approach to health care.  Patient-centered medical homes are
      improving your care by focusing on prevention and teamwork.

PMID- 26219125
TI  - Ask the doctor.  Is it true that losing weight is mostly a matter of calories in,
      calories out?

PMID- 26219126
TI  - Is your medication affecting your thinking skills?  Treatments for blood
      pressure, allergies, and even incontinence may put you at risk for confusion.

PMID- 26219127
TI  - Best exercise for balance:  Tai chi.  Slow, deliberate movements improve your
      stability and protect against falls.

PMID- 26219128
TI  - Author reply.

PMID- 26219129
TI  - Easy way to fit more fiber into meals and snacks.  Focus on whole foods,
      especially fruits and vegetables.

PMID- 26219130
TI  - Pill-free ways to fight urinary incontinence.  New guidelines recommend solutions
      that don't require medication.

PMID- 26219131
TI  - How to prevent and treat dry skin.  Be proactive this winter by moisturizing
      often and avoiding hot water.

PMID- 26219132
TI  - Do you need a vitamin D screening?

PMID- 26219134
TI  - Mediterranean diet linked to longevity, say Harvard researchers.

PMID- 26219133
TI  - Diabetes in midlife may hasten dementia in later life.

PMID- 26219135
TI  - Top 6 ways to get the most out of your doctor visit.  It makes a difference when
      you prepare ahead of time, ask questions, and recap what was discussed.

PMID- 26219136
TI  - A Multifaceted Battle Against Cancer.

PMID- 26219138
TI  - Zero in on Postpartum Hemorrhage to Reduce Cuba's Maternal Mortality.

PMID- 26219137
TI  - The authors reply.

PMID- 26219139
TI  - [Journalist Prize "Evidence based medicine in the media" to Daniela Remus].

PMID- 26219140
TI  - The science of evidence.

PMID- 26219141
TI  - An evaluation of the dentoskeletal effects of slow maxillary expansion from the
      mixed to the permanent dentition.
AB  - INTRODUCTION: The aim of this study was to evaluate the dentoskeletal effects of
      a modified slow maxillary expansion appliance (MSMEA) during the transition from
      the mixed to the permanent dentition. METHODS: Forty subjects presenting with
      posterior crossbites were divided into two groups. Twenty-three subjects were
      assigned to a treatment group (mean age: 9.45 years) and 17 subjects assigned to
      a control group (mean age: 9.25 years). An MSMEA with acrylic occlusal coverage
      limited to the palatal cusps was used to provide maxillary expansion. The mean
      slow expansion treatment period was 7.8 months, while the mean observation period
      continued for 14.8 months of a 22.6-month total study period. RESULTS:
      Substantial dental and skeletal effects were observed following treatment with
      the MSMEA. Most maxillary inter-molar and deciduous inter-second molar width
      increases were maintained in the permanent dentition (91% and 97%, respectively).
      Skeletal maxillary transverse dimensions, which increased by 2 mm after active
      expansion, were significantly greater (p < 0.001) when compared with the
      controls. CONCLUSION: The findings suggested that an MSMEA provided orthopaedic
      and dental effects as a result of posterior crossbite correction. The effects of
      the appliance seen during the mixed dentition were maintained in the permanent
      dentition.

PMID- 26219142
TI  - The effect of topical fluoride varnish on the shear bond strength of orthodontic
      brackets.
AB  - AIM: The present study examined the effect of topical fluoride treatment on the
      shear bond strength (SBS) of orthodontic brackets using single-dose fluoride
      varnishes and assessed according to different post-application times and the
      pattern of debond. METHODS: Of the 105 extracted human mandibular premolars used
      in the study, 70 were subjected to the SBS test and the remaining 35 to the
      Adhesive Remnant Index (ARI) test. The teeth were divided into a control group
      and six test groups: Kolorz ClearShield 5% NaFl varnish Day 1, 8, and 15; and
      Vanish 5% NaFl varnish Day 1, 8, and 15. The samples were coated with their
      respective varnish, following which, brackets were bonded. Each specimen was
      subjected to a shear force in a universal testing machine until failure. Data
      were analysed using the analysis of variance (ANOVA). RESULTS: At all time
      intervals, the mean SBS of the Vanish groups was not significantly different from
      the control group, and the shear strength in the ClearShield groups was
      significantly higher than the control and Vanish groups, except at Day 8 (no
      difference). For the same bonding material, there was no significant difference
      in mean SBS over different time intervals. ARI scores showed no significant
      difference between the groups. CONCLUSION: The application of single-dose
      fluoride varnish, irrespective of the length of time between the fluoride
      treatment and bonding procedure, does not negatively affect the shear bond
      strength of orthodontic brackets.

PMID- 26219143
TI  - The socio-demographic and malocclusion characteristics of adolescents presenting
      for specialist orthodontic treatment in New Zealand practices.
AB  - BACKGROUND: There are few reports of the socio-demographic and malocclusion
      characteristics of those undergoing clinical orthodontic treatment in private
      specialist practice. AIM: To describe the pretreatment characteristics of
      individuals presenting for orthodontic treatment. METHODS: Individuals (N = 174)
      presenting for orthodontic treatment in 19 private specialist orthodontic
      practices in New Zealand were randomly selected and examined (at the beginning of
      a three-year prospective study) and their malocclusions compared using the Dental
      Aesthetic Index (DAI). RESULTS: The mean DAI score was 35.8 (SD 8.4). There were
      no statistically significant socio-demographic differences in DAI score other
      than by household-based socio-economic status (SES), whereby mean scores were
      considerably higher in those of low SES. The majority of patients attending for
      treatment had severe or very severe/handicapping malocclusions. Females had less
      severe malocclusions than males, on average, although the difference was not
      statistically significant. CONCLUSIONS: The malocclusion severity threshold for
      seeking orthodontic treatment appears to be higher in those of lower SES. The
      study findings highlight the need to improve access to orthodontic treatment for
      this group.

PMID- 26219144
TI  - Arch-dimensional changes in non-extraction cases with finishing wires of a
      particular material, size and arch form.
AB  - AIM: This study was undertaken to assess pre- and post-treatment upper and lower
      arch dimensions, and changes occurring in those dimensions, during orthodontic
      treatment without premolar extractions, when finishing wires of a particular
      material, size and arch form had been used. METHODS: The records of 58 patients
      (31 male and 27 female) with a mean age of 13.52 (+/-1.60) years were selected
      for this study, with ethics approval gained from the Departmental Human Ethics
      Advisory Group of the University of Melbourne (DHEAG no: 1033997.1). All patients
      had been treated with fixed appliances (0.018 inch, pre-adjusted edgewise) in the
      early permanent dentition, without premolar extractions, by one experienced
      orthodontist. Pre- and post-treatment upper and lower arch dimensions were
      measured from study casts. Correlation coefficients were calculated between these
      measurements as well as pretreatment cast and vertical cephalometric
      measurements, gender and the amount of crowding that had been relieved. RESULTS:
      Despite the use of finishing archwires of the same material, size and arch form
      (0.016 x 0.022 inch, heat-treated cobalt-chromium), there was considerable
      variation in dimensional changes that occurred during treatment within the total
      sample and its various subgroups, and in the final arch dimensions. All arch
      width changes were found to be strongly correlated with the amount of
      pretreatment crowding. Post-treatment arch dimensions and changes in those
      dimensions were also strongly correlated with pretreatment dimensions, suggesting
      that the final post-treatment arch dimensions were significantly influenced by
      other factors rather than simply the material, size and arch form of the
      finishing wires. In this treated sample, no statistically significant differences
      were found in the resultant arch widths and arch width changes occurring in the
      different vertical pattern sub-groups. CONCLUSION: The placement of finishing
      wires of a particular material, size and arch form is unlikely to result in
      exactly matching end-of-treatment arch forms and dimensions in all orthodontic
      patients. Instead, whether using a 0.018 or a 0.022 inch slot system, the
      clinician should expect considerable individual variation in final arch form and
      dimension, despite the placement of apparently very similar wires. The main
      determinants of final arch form and dimension appear to be the original muscular
      and occlusally-related arch form and dimension and the amount of crowding to be
      relieved. Final arch forms and dimensional changes with treatment are unlikely to
      be directly related to patient gender, age or underlying vertical pattern. The
      findings indicate that clinicians must decide whether they will accept the
      considerable lateral and antero-posterior expansion that is likely to occur when
      crowding is to be relieved in the permanent dentition without premolar
      extractions.

PMID- 26219145
TI  - Evaluation of the mandibular arch in patients with impacted permanent lower
      canines.
AB  - AIM: To determine the features of the mandibular dental arch in subjects
      presenting with impacted permanent lower canines. METHODS: The 'impaction group'
      consisted of 48 Indian subjects with mandibular canine impaction (Females:Males,
      1.5:1; mean age, 15.03 +/- 0.49 years). The 'control group' was comprised of 96
      age-, gender- and malocclusion-matched Indians who were randomly selected from
      subjects initially screened but who had completely erupted mandibular canines.
      Arch width, arch length, arch shape and space status (total tooth size, arch
      length--tooth-size discrepancy) were assessed using dental models and were
      compared between the groups using comparative measurements and statistics.
      RESULTS: Statistically significant differences were demonstrated with respect to
      the arch length, arch shape, total tooth size and arch-length--tooth-size
      discrepancy (p = 0.03, 0.02, 0.04, 0.01; independent 2-sample t-tests,
      respectively). Crowding was more prevalent in subjects with impaction than in the
      controls, with the difference being statistically significant (chi-square =
      13.202; degrees of freedom (df) = 4; p = 0.010). CONCLUSION: Patients with
      permanent mandibular canine impaction have adequately wide but shorter lower
      dental arch forms along with wider mandibular total tooth size and greater arch
      length--tooth-size discrepancy when compared with a control sample.

PMID- 26219146
TI  - An evaluation of the antibacterial properties and shear bond strength of copper
      nanoparticles as a nanofiller in orthodontic adhesive.
AB  - OBJECTIVES: To evaluate the antibacterial properties and effects of an
      orthodontic adhesive containing copper nanoparticles (NPs) on the material's
      shear bond strength. METHODS: Antimicrobial activity was analysed by a disk
      diffusion test against S. aureus, E. coli and S. mutans. The NPs were added to
      the orthodontic adhesive at 0.0100 wt%, 0.0075 wt%, and 0.0050 wt%. Sixty
      extracted bicuspids were divided into two groups and the enamel of all teeth was
      conditioned with phosphoric acid. A coat of moisture insensitive primer (MIP) was
      applied prior to the bonding of brackets with composite resin. Group I served as
      a control and the bonding procedure was performed according to the manufacturer's
      instructions. Group II comprised the test teeth, into which 0.0100 wt% copper NPs
      were included in the MIP. Samples were tested and statistically analysed (p <=
      0.05). The adhesive remnant index (ARI) was also assessed microscopically. -
      RESULTS: The adhesive with copper NPs showed a bactericidal effect against the
      bacteria under study. A significantly higher bond strength was obtained with the
      orthodontic adhesive that included 0.0100 wt% of copper NPs (15.23 +/- 6.8 MPa)
      in comparison with the control group (9.59 +/- 4.3 MPa). The ARI scores indicated
      that the groups were significantly different and strengthened by the
      incorporation of NPs (p = 0.004). CONCLUSION: The results of the present study
      suggested that an orthodontic adhesive, which included copper NPs, significantly
      increased material shear bond strength without adverse side effects on colour and
      appearance. The adhesive interface was strengthened by homogeneously dispersed
      copper NPs added as a nanofiller.

PMID- 26219147
TI  - Location and severity of root resorption related to impacted maxillary canines: a
      cone beam computed tomography (CBCT) evaluation.
AB  - BACKGROUND: The present investigation was designed to determine the location and
      severity of root resorption associated with impacted maxillary canine teeth using
      cone beam computed tomography (CBCT). A secondary aim was to identify possible
      influencing factors. METHODS: The radiological reports of 183 patients,
      radiographed with a small-volume CBCT focussed on the impacted maxillary canine
      teeth, were assessed. Eighty-five patients had resorption associated with the
      impaction. The CBCT image datasets were viewed to determine the location and
      severity of the lesions. RESULTS: A total of 110 impacted maxillary canine teeth
      resorbed 120 adjacent teeth, including 14 premolars and one permanen molar. The
      apical third and palatal surface were commonly involved. Fifty per cent of the
      resorptive lesions were mild, 20% moderate and 30% severe. There was no
      significant relation between age or gender on the number, location or severity of
      resorption. There was a statistically significant correlation between the number
      of impacted canine teeth an'd the number of teeth resorbed, as well as the tooth
      type and the surface involved in the resorption. CONCLUSIONS: All root levels and
      surfaces of teeth associated with impacted maxillary canine teeth can be resorbed
      to different levels of severity. Neither age nor gender influences the number,
      location or severity of the resorption.

PMID- 26219148
TI  - Effects of the Herbst appliance in growing orthodontic patients with different
      underlying vertical patterns.
AB  - INTRODUCTION: The present study involved an assessment of the effects of the
      Herbst appliance used for Class II correction in subjects with different vertical
      facial patterns. METHODS: Pre- and post-treatment lateral cephalograms of 91
      growing Class II patients were divided into three vertical facial groups on the
      basis of mandibular plane angulation. All received a Herbst appliance and dental
      and skeletal changes were assessed in relation to pretreatment incisal overbite,
      overjet and the stage of cervical maturity. RESULTS: Herbst appliance treatment
      was accompanied by changes in the angulation of the upper and lower incisors,
      overjet reduction and an increase in mandibular length. In general, the
      rotational facial changes occurring during treatment were minimal, so that
      dolichofacial patterns remained long and brachyfacial patterns remained short.
      CONCLUSION: Herbst appliance treatment can be expected to result in considerable
      Class II dental correction. It is unlikely, however, that its use will be
      associated with clinically significant forward rotation in dolichofacial
      subjects. Since dolichofacial patterns are likely to remain long-faced, even
      after considerable Class II dental correction, orthognathic surgery may still be
      a consideration if normal facial proportions, without excessive facial convexity
      and lip strain, are treatment aims.

PMID- 26219149
TI  - The orthodontic extraction of permanent molars: a literature review.
AB  - The most common cause of dental crowding is the presence of an arch-length--tooth
      size discrepancy. Conventional methods of gaining space in orthodontics involve
      the extraction of teeth, often premolars. However, there are a number of clinical
      situations in which the extraction of permanent molars might be considered. This
      paper highlights the indications, advantages, disadvantages and timing of the
      extraction of the first, second and third permanent molars in the treatment of a
      crowded malocclusion.

PMID- 26219150
TI  - Innovation in prediction planning for anterior open bite correction.
AB  - This study applies recent advances in 3D virtual imaging for application in the
      prediction planning of dentofacial deformities. Stereo-photogrammetry has been
      used to create virtual and physical models, which are creatively combined in
      planning the surgical correction of anterior open bite. The application of these
      novel methods is demonstrated through the surgical correction of a case.

PMID- 26219151
TI  - Mini-implant-anchored Mesialslider for simultaneous mesialisation and intrusion
      of upper molars in an anterior open bite case: a three-year follow-up.
AB  - BACKGROUND: The present case report describes the orthodontic treatment and long
      term follow-up of an adult female patient (27 years) who was diagnosed with a
      mild Class III malocclusion characterised by an anterior and lateral open bite
      and three periodontally-compromised first permanent molars. AIM: The aim of
      treatment was to provide an acceptable aesthetic and functional occlusion while,
      at the same time, improving the periodontal prognosis. METHODS: The patient was
      treated with fixed orthodontic appliances utilising direct and indirect skeletal
      anchorage derived from two mini-screws placed in the palate and one mandibular
      buccal mini-screw. RESULTS: The objectives of good aesthetics, a functional
      occlusion, a healthy periodontium and a balanced profile were achieved. The total
      treatment time was 31 months, which comprised 13 months of maxillary fixed labial
      appliances and 25 months of mandibular fixed labial appliances. The three-year
      follow-up records showed stability of the Class ILL correction.

PMID- 26219152
TI  - Oro-facial characteristics and the surgical correction of patients affected by
      beta-thalassaemia: a review of the literature and report of a case.
AB  - Despite the fact that recent medical advances have improved the quality of life
      and increased the life expectancy of patients suffering from thalassaemia, no
      standard strategy or clinical guidelines are available for the correction of the
      presenting craniofacial anomalies. The aim of the present study is to review the
      craniofacial features of affected patients, and to discuss the orthodontic and
      orthognathic surgical treatment options available to manage the associated and
      characteristic facial deformity.

PMID- 26219153
TI  - The extraction of maxillary lateral incisors for the treatment of a Class II
      crowded malocclusion: a case report.
AB  - BACKGROUND: The extraction of an upper lateral incisor for orthodontic purposes
      is rare and must be adequately justified. AIM: The present case report describes
      the management of a skeletal Class II crowded malocclusion that was facilitated
      by the extraction of upper lateral incisors and lower first premolars. METHODS: A
      14-year-old male patient presented with a skeletal Class II crowded malocclusion
      with associated speech and chewing difficulties. Phase I of treatment involved
      the extraction of the upper lateral incisors and functional appliance therapy.
      Phase II included the extraction of lower first premolars and mechanotherapy
      using full fixed appliances. RESULTS: An improvement in aesthetics and sagittal
      relations was achieved during phase I therapy as the mandible was advanced over a
      period of eight months. Mandibular skeletal change was 6.5 mm observed at
      pogonion. During phase II therapy, the maxillary canines were substituted for
      lateral incisors and a functional occlusion was achieved. The skeletal correction
      and occlusion were stable one year after debonding. CONCLUSION: The present case
      indicated that the timely extraction of palatally-placed maxillary lateral
      incisors facilitated functional appliance therapy in the management of a skeletal
      Class II problem. The crowding of the lower anterior teeth was relieved and
      alignment of the upper arch was achieved with full fixed appliance therapy,
      resulting in improved aesthetics and a stable occlusion at one year review.

PMID- 26219154
TI  - The adequacy of endometrial sampling: comparison between manual vacuum aspiration
      and metal curettage method.
AB  - OBJECTIVE: To compare-the adequacy of endometrium and the post-procedural pain
      between the manual vacuum aspiration (MVA) and metal curettage method. MATERIAL
      AND METHOD: The present research was a clinical experiment. A randomized
      controlled trial study was done with older than 35-year oldfemales with abnormal
      intrauterine bleeding who attended the out-patient gynecology department of
      Maharat Nakhon Ratchasima Hospital between December 1, 2013 and April 30, 2014.
      Patients were allocated with simple randomization technique into two groups, the
      experimental group was using MVA and the control group was using conventional
      metal uterine curettage. Pain levels were assessed according to the visual
      analogue scale. All tissue samples were examined by pathologists. Statistics used
      were percentage and Chi-square. RESULTS: Percentages of tissue adequacy for
      pathological examination of control and experiment groups were 87.88 and 90.91,
      respectively. There was no significant difference between the two methods (p
      value = 0.572). The patients with severe pain in the experiment group were less
      than that of the control group. The relative risk is 0.47 (95% CI = 0.30-0.72).
      CONCLUSION: MVA caused less pain than the metal curette method, while both
      provided the same rate of adequacy of endometrial tissue sampling for
      pathological diagnosis. The MVA offered more humanized health care for
      gynecological patients who required such procedure. Further researches focusing
      on the cost-effectiveness or medical complications could benefit a practice
      guideline and the health care system for this patient group.

PMID- 26219155
TI  - Cardiometabolic risk in Thai adults with type 2 diabetes mellitus: obese versus
      non-obese.
AB  - BACKGROUND: Adiposity is an inflammatory condition contributing to the morbidity
      and mortality of several disorders, including type 2 diabetes mellitus (T2D) and
      cardiovascular disease. OBJECTIVE: To compare cardiometabolic risk factors
      between obese and non-obese Thai patients with T2DM MATERIAL AND METHOD: The
      cross-sectional study was done in 20 obese (BM >25 kg/m2) and 20 non-obese (BMI
      23 kg/m2) T2DM Researchers measured fasting plasma glucose and lipids, serum
      levels of insulin, leptin, adiponectin, and soluble tumor necrosis factor-alpha
      receptors type 1 and 2 (sTNF-R] andsTNF-R2). Insulin sensitivity check index
      (QUICIKI) and insulin resistance index (HOMA-IR) were calculated. RESULTS: Thai
      obese adults with T2DMhad greater amounts ofsTNF-R2 and HOMA-IR, higher ratios of
      leptin/adiponectin, and more incidences of hypertension and hypertriglyceridemia
      in comparison to non-obese counterparts. Additionally, HOMA-IR values in non
      obese T2DMwere greater than those reported among non-diabetic Thai adults. A
      reverse association between inflammatory markers (both sTNF-Rs) andHDLC was
      detected. Leptin/adiponectin ratios correlated directly with HOMA-IR, serum
      insulin, plasma triglycerides and BMI, whereas HOMA-IR did not relate to any
      studied plasma lipid. CONCLUSION: The present study demonstrated an increased
      cardiometabolic risk in obese T2DM adults than non-obese T2DM adults among the
      Thai population. The leptin/adiponectin ratio may be more relevant to predict the
      risk of cardiovascular events in T2DMpatients than HOMA-IR.

PMID- 26219156
TI  - Antiepileptic Drugs and Bone Health in Thai Children with Epilepsy.
AB  - Background: Epilepsy is the most common neurological disease in children. The
      patient must take antiepileptic drug for controlling the seizure at least 2
      years. Many previous studies show the effect of antiepileptic drug to vitamin D
      status and bone health. OBJECTIVE: To study the prevalence of vitamin D
      deficiency and bone mineral density in the children who are taking antiepileptic
      drug at least 6 months. MATERIAL AND METHOD: Thirty epileptic children who are 3
      18 years old with taking antiepileptic drug at least 6 months and 30 healthy
      children in the same age were performed to investigate serum 25-hydroxyvitamin D,
      calcium, phosphorus, magnesium, creatinine, alkaline phosphatase, albumin,
      parathyroid hormone, spot urine calcium, spot urine phosphorus, spot urine
      creatinine and bone mineral density between October 2012 to September 2013.
      RESULTS: Seven epileptic children (23.3%), eight healthy children (26.7%) have
      vitamin D deficiency. Only 3 epileptic children who are cerebral palsy also have
      low bone mineral density. There is only statistical significant of decreased
      serum albumin (p-value = 0.03) and corrected serum calcium (p-value = 0.04) that
      reveal in epileptic children group. CONCLUSION: Evaluation of serum 25
      hydroxyvitamin D status and bone metabolism is essential in the treatment of
      childhood epilepsy.

PMID- 26219157
TI  - Growth Hormone (GH) Retesting and Final Adult Height in Childhood-Onset GH
      Deficiency (CO-GHD): Experiences from King Chulalongkorn Memorial Hospital,
      Thailand.
AB  - OBJECTIVE: Evaluate GHstatus in CO-GHD subjects after completion of linear
      growth, and report the auxological outcomes of rhGH treatment. MATERIAL AND
      METHOD: Twenty-four CO-GHD subjects (14 with IGHD and 10 with MPHD), treated with
      rhGH for a period of 6.6 +/- 3.1 years were re-evaluated for their capacity of GH
      secretion by performing insulin tolerance test (ITT). Ht SDS at final height was
      compared with Ht SDS at the start of the treatment and MPH SDS. RESULTS: Thirty
      eight percent (9 in 24) of CO-GHD subjects had normal GH secretion on retesting.
      All subjects were diagnosed as isolated GHD during childhood. In contrast, all
      MPHD subjects during childhood period had GH insufficiency on retesting. GH
      insufficient subjects had higher total cholesterol level than those with GH
      sufficiency (214 +/- 51 vs. 1 74 +/- 36 mg/mL, p = 0.03). rhGH treatment
      significantly increased Ht SDS of -2.0 +/- 1.1 at the start of the treatment to 
      0.6 +/- 1.3 at the end of the treatment (p < 0.01) and -0.8 +/- 1.2 at GH
      retesting (p < 0.01). CONCLUSION: GH retesting is recommended in subjects with
      IGHD during the childhood period. However rhGH treatment can enhance the final
      height in both GH sufficient and insufficient subjects on retesting.

PMID- 26219158
TI  - The Influence of VKORC1 Polymorphisms on Warfarin Doses in Thai Patients with
      Deep Vein Thrombosis.
AB  - BACKGROUND: Polymorphisms in cytochrome P450 2C9 and vitamin K epoxide reductase
      complex, subunit 1 genes (CYP2C9 and VKORC1, respectively) were previously shown
      to affect the warfarin dose required in anticoagulant therapy of deep vein
      thrombosis (DVT). However, little is known about the role of these genetic
      variants in the Thai population. OBJECTIVE: To identify the effect of CYP2C9 and
      VKORC1 genetic variants on warfarin dosage in the Thai population with DVT.
      MATERIAL AND METHOD: Genotyping of CYP2C9 (*2 and *3) and VKORC1 promoter (-1
      639G>A) variants were carried out in 97 Thai DVT patients receiving constant
      warfarin therapy and with a stable international normalized ratio using real-time
      PCR assays. RESULTS: VKORC1 AA, GA, and GG genotype frequencies were found to be
      49.5%, 46.4%, and 4.1%, respectively, while those of CYP2C9 genotypes were 88.7%
      for *1/*1 and 11.3%for *1/*3. The CYP2C9*2 variant was not present in the
      patients studied. The mean daily warfarin dose required to maintain a therapeutic
      INR differed significantly according to VKORC1 genotype, with 3.6 mg/day required
      for AA, 4.7 mg/day for GA, and 7.4 mg/day for GG (p-value < 0.001). The CYP2C9
      genotype did not significantly affect the warfarin dosage requirement (p-value =
      0.29). CONCLUSION: These findings underline the impact of VKORC1 genotypes on the
      wide variation in warfarin maintenance dosing in Thai patients with DVT.

PMID- 26219159
TI  - The Anterior Cruciate Ligament Reconstruction with the Peroneus Longus Tendon: A
      Biomechanical and Clinical Evaluation of the Donor Ankle Morbidity.
AB  - BACKGROUND: The purpose of this study was to report on ankle and foot functions
      via the holistic evaluations using clinical examination, functional scores
      assessment and isokinetic tests after harvesting autogenous peroneus longus
      tendons for anterior cruciate ligament (ACL) reconstruction focusing on the donor
      site morbidity with a minimum 1-year follow-up period. MATERIAL AND METHOD: The
      study included 24 patients who underwent ACL reconstruction using peroneus longus
      autograft and endobutton fixation. Results of ACL reconstruction were assessed
      via physical examination. Donor site morbidity of the foot and ankle after tendon
      harvesting was assessed using American Orthopedic Foot-and-Ankle Society (AOFAS)
      for ankle-hindfoot score and Visual Analogue Score-Foot Ankle (VAS-FA).
      Isokinetic testing for the ankle was performed in 10 voluntary patients after
      surgery. RESULTS: Mean follow-up time was 12.8 months. Regarding the latest
      follow-up, anterior drawer tests of ankle showed normal findings in 83.3%, and 1+
      anterior laxity in 16.7% of all patients. Mean pre- and postoperative AOFAS
      scores were 100.0 +/- 0.0 and 96.0 +/- 9.6, respectively at 6-month follow-up (p
      = 0.06). Mean pre- and postoperative VAS-FA scores were 99.7 +/- 1.1 and 95.4 +/-
      12.0, respectively at - 13-month follow-up (p = 0.09). At 7-month follow-up by
      isokinetic testing, peak torques of eversion and inversion were significantly
      lower on the harvested ankle compared with the contralateral ankle at both
      velocities (60 degrees/second and 120 degrees/second, p < 0.05). CONCLUSION:
      Based on overall findings in the present study, the authors could not recommend
      the peroneus longus tendon as the first option of donor graft for ACL
      reconstruction due to the several morbidities particularly in the first 12 months
      after the operation. However, the peroneus longus tendon may be the option after
      other graft harvestings for the ligament reconstruction, which needs several
      tendon grafts in a patient with multi-directional instability of the knee due to
      some specific situation such as a traumatic knee dislocation.

PMID- 26219160
TI  - Validity and Reliability of Thai Version of the Foot and Ankle Ability Measure
      (FAAM) Subjective Form.
AB  - BACKGROUND: Self-administered questionnaires have become an important aspect for
      clinical outcome assessment of foot and ankle-related problems. The Foot and
      Ankle Ability Measure (FAAM) subjective form is a region-specific questionnaire
      that is widely used and has sufficient validity and reliability from previous
      studies. OBJECTIVE: Translate the original English version of FAAM into a Thai
      version and evaluate the validity and reliability of Thai FAAM in patients with
      foot and ankle-related problems. MATERIAL AND METHOD: The FAAM subjective form
      was translated into Thai using forward-backward translation protocol. Afterward,
      reliability and validity were tested. Following responses from 60 consecutive
      patients on two questionnaires, the Thai FAAM subjective form and the short form
      (SF)-36, were used. The validity was tested by correlating the scores from both
      questionnaires. The reliability was adopted by measuring the test-retest
      reliability and internal consistency. RESULTS: Thai FAAM score including activity
      of daily life (ADL) and Sport subscale demonstrated the sufficient correlations
      with physical functioning (PF) and physical composite score (PCS) domains of the
      SF-36 (statistically significant with p < 0.001 level and >= 0.5 values). The
      result of reliability revealed highly intra-class correlation coefficient as 0.8
      and 0.77, respectively from test-retest study. The internal consistency was
      strong (Cronbach alpha = 0.94 and 0.88, respectively). CONCLUSION: The Thai
      version of FAAM subjective form retained the characteristics of the original
      version and has proved a reliable evaluation instrument for patients with foot
      and ankle-related problems.

PMID- 26219161
TI  - The Impact of Different Anesthesia Methods on Stress Reaction and Immune Function
      of the Patients with Gastric Cancer during Peri-Operative Period.
AB  - OBJECTIVE: To explore a better anesthesia method for the patients with gastric
      cancer who will undergo operation by investigating the impact of different
      anesthesia methods on stress reaction and immune function. MATERIAL AND METHOD:
      The present prospective study was carried out in Xiangyang Central Hospital,
      China, between January 2008 and August 2014. Sixty-four cases of antral
      carcinoma, subjected to radical resection of gastric cancer were randomly divided
      into general anesthesia group (GA group) and general anesthesia combined with
      continuous epidural anesthesia group (GCEA group). The peripheral venous bloods
      were sampled to determine the content of TNF-alpha, IL-6, IL-8, T-lymphocyte
      subsets, and natural killer (NK) cells. The data was analyzed by SPSS 13.0.
      RESULTS: After operation, the content of TNF-alpha, IL-6, and IL-8 in GCEA group
      were significant lower than that in GA group (p < 0.05). At the end ofthe
      operation, the content of T-lymphocyte subsets and NK cells in GA and GCEA groups
      descended significantly, but GA group was larger (p < 0.01 vs. p < 0.05). Seventy
      two hours after the operation, the content of T-lymphocyte subsets and NK cells
      in GCEA group were back to normal, but it was significantly lower than before
      anesthesia (p < 0.05) in the GA group. CONCLUSION: Compared to GA, GCEA is a
      better anesthesia method for gastric cancer patient who will undergo operation
      because it has lower stress reaction and less impact on immune function.

PMID- 26219162
TI  - Alternative Landmarks of the Mandibular Foramen to Prevent Nerve Injury during
      Ramus Surgery.
AB  - OBJECTIVE: To investigate the mandibular foramen (MF) position in relation to
      other bony landmarks on the mandibular ramus (MR) to better understand the
      anatomical landmark during the ramus surgery. MATERIAL AND METHOD: Ninety-two
      adult mandibles were studied by measuring four linear parameters: AB, the
      distance from the posterior limit of the MF (point A) to the posterior border of
      the MR (point B), BC, the MR width (Point C was located at the anterior border of
      the MR), DE, the distance from the lingula tip (the highest and the most anterior
      limit of the MF) (point D) to the mandibular notch (point E), and the MR height
      (EF, point F was located at the mandibular inferior border). Lines BC and EF were
      drawn through points A and D and parallel to the inferior and posterior borders
      of the mandible, respectively. These measurements were analyzed to determine the
      mean parameters related to the MF location. RESULTS: The mean lengths of AB, BC,
      DE, and EF were 12.7 +/- 2.3, 35.0 +/- 4.0, 17.5 +/- 3.5, and 52.7 +/- 5.2 mm,
      respectively. The ratios between AB/BC and DE/EF were 0.36 +/- 0.05 and 0.33 +/-
      0.05, respectively. This study indicated that the MF located slightly anterior to
      the posterior third of the MR width and at the superior third of the MR height.
      CONCLUSION: Anatomical consideration of this area is useful to prevent
      neurovascular injury when performing the bony cut made in a ramus osteotomy;
      however, pre-operative examinations with appropriate radiographic analysis are
      also recommended.

PMID- 26219163
TI  - Decontamination Efficacy of Ultraviolet Radiation against Biofilms of Common
      Nosocomial Bacteria.
AB  - BACKGROUND: Ultraviolet radiation (UV) is commonly used to destroy microorganisms
      in the health-care environment. However, the efficacy of UV radiation against
      bacteria growing within biofilms has never been studied. OBJECTIVE: To measure
      the sterilization effectiveness of UV radiation against common healthcare
      associated pathogens growing within biofilms. MATERIAL AND METHOD: Staphylococcus
      aureus, Methicillin-resistant S. aureus (MRSA), Streptococcus epidermidis,
      Escherichia coli, ESBL-producing E. coli, Pseudomonas aeruginosa and
      Acinetobacter baumannii were cultivated in the Calgary Biofilm Device. Their
      biofilms were placed 50 cm from the UV lamp within the Biosafety Cabinet.
      Viability test, crystal violet assay and a scanning electron microscope were used
      to evaluate the germicidal efficacy. RESULTS: Within 5 minutes, UV radiation
      could kill S. aureus, MRSA, S. epidermidis, A. baumannii and ESBL-producing E.
      coli completely while it required 20 minutes and 30 minutes respectively to kill
      E. coli and P. aeruginosa. However, the amounts of biomass and the ultrastructure
      between UV-exposed biofilms and controls were not significantly different.
      CONCLUSION: UV radiation is effective in inactivating nosocomial pathogens grown
      within biofilms, but not removing biofilms and EPS. The biofilm of P. aeruginosa
      was the most durable.

PMID- 26219164
TI  - Effect of Breast Sling Use on Transthoracic Echocardiographic Examination Time
      and Image Quality in Women with Large Breasts.
AB  - BACKGROUND: Transthoracic echocardiographic examinations in women with large
      breasts are technically demanding and can lead to suboptimal image quality,
      excessive scan time, and cause pain and discomfort to patients. OBJECTIVE:
      Evaluate the effects of self-made breast sling used during transthoracic
      echocardiographic examination on scanning time, image quality, pain, and
      satisfaction in women with large breasts. MATERIAL AND METHOD: A self-made breast
      sling was developed by the study team and tested in 26 women with bra cup size of
      C or larger, who were scheduled for transthoracic echocardiography. Each patient
      underwent transthoracic echocardiographic examination twice, with and without
      breast sling use. The sequence of the examinations was determined at random. The
      primary outcome was scan time in apical views. Secondary outcomes included total
      scan time, image quality in apical views (qualitative scores), patients' and
      sonographers' pain (qualitative scores), and patients' satisfaction (qualitative
      scores). Outcomes were compared within individual subjects. RESULTS: The use of
      self-made breast sling did not reduce scan time in apical views (mean difference
      2.8 minutes, p = 0.053), but it reduced total scan time (mean difference 5.9
      minutes, p = 0.04). Breast sling use was not associated with improvement in image
      quality scores (p = 0.59), patients' pain (p = 0.21), and sonographers' shoulder
      back-neck pain (p = 0.052). It improved patients' satisfaction (p = 0.01) and
      sonographers' wrist pain (p = 0.035). CONCLUSION: In women with large breasts who
      required transthoracic echocardiographic examination, the use of self-made breast
      sling did not improve scan time and image quality in apical views. It may improve
      total scan time, patients' satisfaction, and sonographers' wrist pain.

PMID- 26219165
TI  - Utility of Adding SPECT/CT Imaging to Post-Therapeutic Radioiodine Whole-Body
      Scan in Patients with Differentiated Thyroid Cancer.
AB  - OBJECTIVE: To determine the usefulness of adding single-photon emission computed
      tomography/computed tomography (SPECT/CT) imaging to post-therapeutic radioiodine
      whole-body scan (RxWBS) in patients with differentiated thyroid cancer. MATERIAL
      AND METHOD: RxWBSs and SPECT/CT images of 93 consecutive patients were reviewed
      retrospectively by three experienced nuclear medicine physicians without
      knowledge of clinical data. RxWBSs were reviewed first followed by evaluation of
      RxWBS plus SPECT/CT imaging. Foci of increased radioiodine uptake were identified
      and localization was attempted. The findings obtained from RxWBS were compared
      with WBS plus SPECT/CT imaging to determine impact on lesion characterization,
      TNM staging, and management plan. RESULTS: Two hundred seventy seven lesions were
      identified by RxWBS alone. RxWBS plus SPECT/CT imaging detected eight additional
      pathologic lesions (4 in bones, two in neck, and one in lung and thyroid bed).
      RxWBS plus SPECT/CT studies reclassified 85 of 277 lesions (30.7%) detected by
      RxWBS. Most change occurred in neck region (57 lesions) followed by chest region
      (16 lesions). For impact on TNM staging, RxWBS plus SPECT/CT studies changed N
      stage of 21 patients (22.6%) and reclassified M stage of 10 patients (10.8%).
      These resulted in change of TNM stage group of 14 patients (15.1%) and changed
      management plan of 19 patients (20.4%). CONCLUSION: The addition of SPECT/CT
      imaging to RxWBS in patients with differentiated thyroid cancer improved disease
      localization and lesion characterization leading to more accurate N and M
      staging, which was mainly downstaged. SPECT/CT also had impact on plan of
      management in about one fifth of the patients. However, caution should be taken
      when interpreting lesion in lower chest and upper abdomen because misregistration
      of SPECT and CT images.

PMID- 26219166
TI  - Vancomycin Dosing Regimen by Monte Carlo Simulation in Patients on Intermittent
      High-Efficiency Hemodialysis (HEHD).
AB  - OBJECTIVE: To evaluate the effective vancomycin dosing regimens by Monte Carlo
      simulation among patients on intermittent high-efficiency hemodialysis (HEHD).
      MATERIAL AND METHOD: The present study was conducted on eight end-stage renal
      disease patients receiving HEHD. The patients received an initial dose of
      vancomycin 1 g followedby 500 mg immediately after HEHD session for a
      supplementation. Blood samplings were obtained to investigate vancomycin
      pharmacokinetic parameters. A Monte Carlo simulation was performed to determine
      the percentage of probability of target attainment (PTA) achieving AUC24/MIC
      ratio greater than or equal to 400 as the target of achievement of antimicrobial
      activity. RESULTS: A loading dose (LD) of vancomycin of 20 mg per kilogram of dry
      weight (DW) with or without a supplementation had the optimum effectiveness for
      pathogens with MICs not greater than 0.5 mg/L. For pathogens with an MIC of 1.0
      mg/L, the LD of 25 mg/kgDW followed by 20 or 25 mg/kgDW supplementation was
      achieved the target in some cases. Therefore, the LD of 30 mg/kgDW followed by 25
      mg/kgDW or the LD of 35 mg/kgDW with 10, 20 or 25 mg/kgDW supplementation was
      required to achieve the target of antimicrobial activity. CONCLUSION: From the
      present study, the lowest vancomycin dosing regimen that had the optimum
      effectiveness was a 35 mg/kgDW LD followed by 10 mg/kgDW supplementation. This
      regimen is recommended to treat pathogens with MICs not greater than 1.0 mg/L.

PMID- 26219167
TI  - A Woman with Recurrent Hemoptysis, a Rare Etiology.
AB  - Bronchopulmonary endometriosis is a rare clinical entity of thoracic
      endometriosis syndrome (TES). The diagnosis is often delayed because of high
      index of clinical suspicion is needed. We submit a case of 32-year-old healthy
      woman presenting with recurrent non-massive hemoptysis with the onset of menses
      for six months. Computed tomography scans of the chest revealed ill-defined
      ground glass opacity in superior segment of right lower lobe. Fiberoptic
      bronchoscopy was performed during the menstruation showed diffuse erythema along
      distal trachea through lobar bronchus. These findings disappeared when repeated
      at the end of menstrual cycle. Cytologic findings of bronchial wash suggested the
      evidence of old hemorrhage and the endometrial cells. After treatment with depot
      medroxyprogesterone acetate, hemoptysis did not occur for 12 months of follow-up.
      Based on clinical features and response to treatment, bronchopulmonay
      endometriosis was diagnosed.

PMID- 26219168
TI  - Outcomes of Arterial Embolization of Adrenal Tumor in Siriraj Hospital: Case
      Report.
AB  - OBJECTIVE: To evaluate the treatment outcome of arterial embolization in adrenal
      tumor MATERIAL AND METHOD: Clinical records of patients with adrenal tumor who
      underwent adrenal arterial embolization with pre- and post-embolization computed
      tomography (CT) imaging at Siriraj Hospital, between 2007 and 2013 were
      retrospectively reviewed. RESULTS: Five sessions of embolization were performed
      in three patients. The superior adrenal artery was occluded in two patients, the
      middle adrenal artery in two sessions in one patient, and inferior adrenal artery
      in two patients. Adrenal arterial embolization successfully reduced tumor
      vascularity in all patients. The pain relief in all patients was the effect of
      embolization and complete cessation of retroperitoneal bleeding from ruptured
      myelolipoma in one patient. There are no late complications such as pleural
      effusion, adrenal insufficiency, or abscess. CONCLUSION: Adrenal arterial
      embolization is a good choice for adjunctive or palliative treatment of
      unresectable adrenal tumor in particular conditions such as palliative pain
      control, ruptured adrenal tumor with retroperitoneal hemorrhage, or reduction of
      tumor vascularity. Even if embolization is not able to reduce tumor size, it is
      an effective initial treatment before further management, without serious
      complication.

PMID- 26219169
TI  - Other View on Conceptive Options for People Living with HIV.

PMID- 26219170
TI  - The Royal Road to Time: How Understanding of the Evolution of Time in the Brain
      Addresses Memory, Dreaming, Flow, and Other Psychological Phenomena.
AB  - It has been claimed that dreams are the royal road to the unconscious mind. The
      present work argues that dreams and associated brain states such as memory,
      attention, flow, and perhaps even consciousness itself arise from diverse
      conflicts over control of time in the brain. Dreams are the brain's offline
      efforts to distill projections of the future, while memory represents the
      vestiges of the past successes and survived failures of those and other conscious
      projections. Memory thus acts to inform and improve the prediction of possible
      future states through the use of conscious prospects (planning) and unconscious
      prospective memory (dreams). When successful, these prospects result in states of
      flow for conscious planning and deja vu for its unconscious comparator. In
      consequence, and contrary to normal expectation, memory is overwhelmingly
      oriented to deal with the future. Consciousness is the comparable process
      operating in the present moment. Thus past, present, and future are homeomorphic
      with the parts of memory (episodic and autobiographical) that recall a personal
      past, consciousness, and the differing dimensions of prospective memory to plan
      for future circumstances, respectively. Dreaming (i.e., unconscious prospective
      memory), has the luxury to run multiple "what if" simulations of many possible
      futures, essentially offline. I explicate these propositions and their relations
      to allied constructs such as deja vu and flow. More generally, I propose that
      what appear to us as a range of normal psychological experiences are actually
      manifestations of an ongoing pathological battle for control within the brain.
      The landscape of this conflict is time. I suggest that there are at least 3
      general systems bidding for this control, and in the process of evolution, each
      system has individually conferred a sequentially increasing survival advantage,
      but only at the expense of a still incomplete functional integration. Through
      juxtaposition of these respective brain systems, I endeavor to resolve some
      fundamental paradoxes and conundrums expressed in the basic psychological and
      behavioral processes of sleep, consciousness, and memory. The implication of this
      conceptual framework for the overall conception of time is then briefly
      adumbrated.

PMID- 26219171
TI  - Awareness of "Invisible" Arrows in a Metacontrast Masking Paradigm.
AB  - A common strategy in unconscious perception research is to use either pattern
      masking or metacontrast masking to render prime stimuli "invisible" to
      consciousness. However, several recent studies have questioned whether the
      identities of prime stimuli (typically arrows or diamonds and squares) in
      metacontrast masking studies are impossible to consciously perceive. In a series
      of studies, we concurrently related prime awareness, target response time
      priming, and prime identification across 3 prime-mask stimulus onset asynchronies
      (27, 40, and 67 ms). We found that increases in prime awareness ratings were
      accompanied by better prime identification performance. Significant prime
      identification in the 27-ms condition was obtained only at the highest awareness
      rating; for the other 2 stimulus onset asynchronies most awareness ratings were
      associated with above-chance prime identification. The priming effects obtained
      in these paradigms occur, to some degree, when participants are likely to be
      aware of the prime stimuli. Our results, collectively, suggest that metacontrast
      masking of primes does not necessarily preclude their awareness. Priming effects
      may depend on at least partial awareness of the prime stimuli.

PMID- 26219172
TI  - The Relation of Alexithymic Traits to Affective Theory of Mind.
AB  - Little research has focused on the contributors to adult theory of mind (ToM)
      even though there is reason to suspect individual differences in performance in
      neurotypical samples. Alexithymia, a term that references an impaired ability to
      attend to and verbally label emotions via ongoing introspection, is a useful
      construct through which to explore how socially relevant dimensions of emotion
      processing enable ToM. As 1 study has explored alexithymia vis-a-vis cognitive
      ToM, this study examined the relationships between facets of alexithymia and
      affective ToM while controlling for the potential confounds of empathy, verbal
      ability, and negative affect. A nonclinical sample of adults (N = 86) completed
      the Toronto Alexithymia Scale, the Reading the Mind in the Eyes Test, the
      Mehrabian and Epstein Scale of Emotional Empathy, the Profile of Mood States, and
      the Wechsler Abbreviated Scale of Intelligence. Hierarchical regression analysis
      showed that externally oriented thinking contributed unique variance to affective
      ToM, confirming an inverse relationship between alexithymia and affective ToM but
      highlighting the need to parse alexithymia into discrete facets when exploring
      its relevance to social cognition.

PMID- 26219174
TI  - Studying the Existence and Attributes of Consensus on Psychological Concepts by a
      Cognitive Psychometric Model.
AB  - Psychological research can take a variety of directions while building on
      theoretical concepts that are commonly shared among the population of
      researchers. We investigate the question of how agreement or consensus on basic
      scientific concepts can be measured. Our approach to the problem is based on a
      state-of-the-art cognitive psychometric technique, implemented in the theoretical
      framework of cultural consensus theory. With this approach, consensus-based
      answers for questions exploring shared knowledge can be derived while basic
      factors of the human decision-making process are accounted for. An example of the
      approach is provided by examining the definition of behavior, based on responses
      from researchers and students. We conclude that the consensus definition of
      behavior is "a response by the whole individual to external or internal stimulus,
      influenced by the internal processes of the individual, and is typically not a
      developmental change." The general goal of the article is to demonstrate the
      utility of a cultural consensus theory-based approach as a method for
      investigating what current, working definitions of scientific concepts are.

PMID- 26219173
TI  - Controlled Retrieval of Specific Context Information in Children and Adults.
AB  - This study adapted a procedure used by Luo and Craik (2009) to examine whether
      developmental differences exist in the ability to use controlled retrieval
      processes to access the contextual details of memory representations.
      Participants from 3 age groups (mean ages 9, 12, and 25 years) were presented
      with words in 3 study contexts: with a black-and-white picture, with a color
      picture, or alone without a picture. Six recognition tests were then presented
      that varied in the demands (high or low) placed on the retrieval of specific
      contextual information. Each test consisted of a mixture of words that were old
      targets from 1 study context, distractors (i.e., previously studied words from a
      different context), and completely new words. A high-specificity and a low
      specificity test list was paired with each test question, with high and low
      specificity being determined by the nature of the distractors used in a test
      list. High-specificity tests contained words that were studied in similar
      contexts: old targets (e.g., words studied with black-and-white pictures) and
      distractors (e.g., words studied with color pictures). In contrast, low
      specificity tests contained words that were studied in dissimilar contexts: old
      targets (e.g., words studied with black-and-white pictures) and distractors
      (e.g., words previously studied without a picture). Relative to low-specificity
      tests, the retrieval conditions of high-specificity tests were assumed to place
      greater demands on the controlled access of specific contextual information.
      Analysis of recollection scores revealed that age differences were present on
      high-but not low-specificity tests, with the performance of 9-year-olds
      disproportionately affected by the retrieval demands of high-specificity tests.

PMID- 26219175
TI  - When Do We Use Automatic Tools Rather Than Doing a Task Manually? Influence of
      Automatic Tool Speed.
AB  - In our everyday lives we tend to minimize effort, by using automatic tools, for
      instance. But we also tend to avoid idleness by engaging in various activities.
      What happens when minimizing effort and avoiding idleness are concurrent? This
      article explores the influence of waiting time as compared with a fixed manual
      task completion on people's preference for waiting or doing the task. In 2
      experiments, participants were asked to choose performing a manual task or
      waiting while an automatic tool performed the task for them. The time required by
      the automatic tool to complete the task was manipulated and was equal to or
      shorter than the time needed for manual completion. Results indicated that the
      faster the automatic tool (i.e., the shorter the waiting time) the more
      participants used it instead of doing the task manually. However, participants
      favored the waiting option only when the waiting time was less than half as long
      as doing the task manually. These results suggest that people prefer to avoid
      idleness rather than to minimize effort.

PMID- 26219176
TI  - Local and Global Task Switching Costs in Bilinguals Who Vary in Second Language
      Proficiency.
AB  - We examined the relationship between bilinguals' second language (L2) proficiency
      and their performance on a Stroop switching task, in which a color word (e.g.,
      GREEN) appeared in a congruent ink color (e.g., green) or an incongruent ink
      color (e.g., red). Participants either read aloud the color word in the word
      reading trials or named the ink color in the color-naming trials. Bilinguals who
      varied in L2 proficiency received 2 pure blocks, consisting of word-reading
      trials and color-naming trials, respectively, and 1 mixed block, consisting of
      intermixed word-reading and color-naming trials in an alternating-runs pattern.
      Comparing performance in nonswitch trials in the mixed block and the pure block
      provides a measure of global switch costs, whereas differences on switch trials
      and nonswitch trials in the mixed block reflect local switch costs. Bilinguals
      with higher L2 proficiency showed a marginally smaller Stroop effect in color
      naming, a smaller local switch cost in word reading (but not in color naming),
      and a smaller word-reading versus color-naming task set asymmetry in local switch
      costs. The latter result was consistent with the language switching finding that
      the L1/L2 switch cost asymmetry decreased as a function of bilinguals' L2
      proficiency. Overall, the current findings support the facilitative role of L2
      proficiency in bilinguals' task set switching: Those with higher L2 proficiency
      have better task set shifting and reconfiguration and updating abilities when
      they switch from a more difficult task set (color naming) to an easier task set
      (word reading) in a task-switching paradigm.

PMID- 26219177
TI  - Effects of Self-Objectification on Self-Reported Eating Pathology and Depression.
AB  - Self-objectification occurs when people internalize an observer's perspective
      onto their own bodies. This study experimentally examined the impacts of self
      objectification on 156 male and female college students. We induced a state of
      self-objectification by having undergraduate students in an experimental
      condition describe their bodies in writing, from an observer's viewpoint.
      Participants then completed a questionnaire measuring self-reported eating
      pathology and depression. When compared with a control group, the self
      objectification manipulation caused an increase in self-reported eating pathology
      in both men and women. The results support previous research finding broad,
      negative impacts of self-objectification.

PMID- 26219180
TI  - Consenting to budgeted plans for redevelopment of the School of Dentistry.

PMID- 26219181
TI  - Factors influencing the use of oral health services among adolescents in New
      Zealand.
AB  - OBJECTIVES: This study investigated the impact of parental use of dental
      services, ethnicity and socio-economic background on adolescents' recent use of
      dental services. DESIGN: Secondary analysis of cross-sectional data from the 2009
      New Zealand Oral Health Survey (2009 NZOHS). PARTICIPANTS/MATERIALS AND METHODS:
      A sub-sample of all adolescent participants aged 12-17 years (n = 509) from the
      nationally representative 2009 NZOHS. The NZOHS included self-report data on oral
      health status, risks and protective factors, and utilisation of oral health
      services. MAIN OUTCOME MEASURES: Outcome measures were 'most recent dental visit'
      and 'type of provider last visited'. Key exposure factors were 'most recent
      dental visit by primary caregiver' (among 12-14-year-olds), ethnicity, and
      socioeconomic deprivation. Univariate analysis for each outcome was conducted
      using survey-weighted estimates, followed by multivariable analysis using
      logistic regression. RESULTS: Four in five adolescents reported having visited a
      dental provider within the last year (79.9%), with almost half having last
      visited a private general dental practice (46.6%). No significant associations
      were found for either outcome with the primary caregiver exposure factor (Most
      recent dental visit outcome fully adjusted OR (primary caregiver not visited) =
      0.93, 95% CI 0.32, 2.72; Visited provider other than private general dental
      practice outcome fully adjusted OR (primary caregiver not visited) = 1.60, 95% CI
      0.39, 6.57). Compared to European/Other adolescents, Maori and Pacific
      adolescents were significantly more likely to have not visited in the last year
      (Maori 12-14 years fully adjusted OR = 4.20, 95% CI 1.54, 11.50; Pacific 12-17
      years fully adjusted OR = 2.61, 95% CI 0.84, 8.07--the latter was not significant
      after adjusting for socioeconomic deprivation), and significantly less likely to
      have last visited a private general dental practice (Maori 12-17 years fully
      adjusted OR = 2.16, 95% CI 1.13, 4.12; Pacific 12-17 years fully adjusted OR =
      5.15, 95% CI 1.69, 15.74). CONCLUSION: Ethnicity was strongly associated with use
      of oral health services among New Zealand adolescents. No statistically
      significant evidence was found that primary caregiver use of oral health services
      or socioeconomic deprivation were impacting on adolescent uptake of oral health
      services.

PMID- 26219182
TI  - Direct pulp capping of permanent teeth in New Zealand general dental practice--a
      practice based research study.
AB  - OBJECTIVES: This study aimed to investigate treatment protocols and opinions
      towards direct pulp capping (DPC) amongst New Zealand (NZ) general dental
      practitioners (GDP) through a Practice Based Research Network (PBRN) study.
      DESIGN: Mixed-methods approach using qualitative thematic and quantitative
      analysis. METHODS: An on-line survey containing Likert scale items and open-ended
      questions was distributed to GDPs on the Dental Council of New Zealand (DCNZ)
      register (2012) to collect information on practitioner demographics, treatment
      protocols, continuing professional development (CPD) and philosophies towards
      DPC. RESULTs: Two hundred and ten GDPs from North and South Islands providing
      care in main centres and rural areas engaged with the PBRN and participated in
      the study. Almost all performed DPC treatment although it was not a common
      procedure. DPC was perceived as 'successful' or 'very successful' by 95% of
      respondents, mostly for cases of reversible pulpitis. Most provided DPC for
      patients of all ages but younger patients were perceived to have the best
      clinical outcomes. Calcium hydroxide and MTA were the most commonly used
      materials for DPC. MTA was believed to have the best outcome but cost and
      handling properties were barriers to its use. The majority of respondents had
      participated in CPD related to vital pulp therapy and regarded this treatment as
      conservative and providing time and financial benefits compared with more
      invasive treatment. Clinicians' timeframes for assessing healing were variable,
      and combined clinical and radiographic findings were considered most useful.
      CONCLUSION: New Zealand dentists perceive DPC as a successful and conservative
      treatment in selected cases. The findings have provided insights into engagement
      of NZ dentists in using research to inform everyday clinical practice through a
      PBRN study.

PMID- 26219183
TI  - A qualitative study of the meaning of oral health and self-care for 40 Dunedin
      residents living on lower incomes.
AB  - BACKGROUND AND OBJECTIVES: This project extends studies of oral health cultures
      for lower income families by identifying the participants' meaning of oral health
      self-care, barriers to its attainment, and suggestions for its improvement.
      METHODS: Forty open-ended interviews were conducted with Dunedin residents
      purposively selected from a variety of ages, backgrounds and ethnicities.
      Transcribed interviews were analysed thematically. RESULTS: Five key themes
      emerged: (1) oral health understandings for self and wider family groups; (2) the
      complexity of understanding cost in relation to oral self-care; (3) oral self
      care tools and daily oral health routines; (4) relationships with oral health
      workers and the meaning of good and bad care provision; and (5) the State's
      involvement in oral health. CONCLUSIONS: Participants valued good oral health and
      were knowledgeable about it, but cost was the primary barrier to care.

PMID- 26219184
TI  - Trends in paediatric maxillofacial trauma presenting to Dunedin Hospital, 2006 to
      2012.
AB  - OBJECTIVES: The purpose of this study was to review the epidemiology, aetiology
      and management of maxillofacial injuries in the paediatric population seen in
      Dunedin, New Zealand from 2006 to 2012. MATERIALS AND METHODS: A retrospective
      descriptive analysis was conducted over a 7 year period. Data concerning
      demographics, injuries and management of patients between the ages of 0-17 years
      who presented to the oral and maxillofacial service in Dunedin were gathered and
      analysed. RESULTS: 340 incidents that excluded pure dental trauma were recorded.
      Falls were found to be the most common cause of injury; followed by contact with
      animate objects (other individuals and animals), contact with inanimate objects
      and road traffic accidents. Injuries in younger age groups were found to be
      caused by falls and contact with inanimate objects more often, receiving
      predominantly soft tissue injuries. In the older age group, a higher number of
      facial fractures were seen with a change in the most common causes to road
      traffic accidents and contact with animate objects. An increase in alcohol
      related road traffic accidents was noted among females. For all injuries the male
      to female ratio was 2:1 which is similar to previous reports from New Zealand and
      overseas. For the sub group of facial fractures a much higher ratio of males were
      seen at a ratio of 8.5:1. CONCLUSIONS: Causes of injury and anatomical location
      followed similar patterns to reports worldwide, along with a similar male to
      female ratio. Although the incidence of road traffic accident related facial
      injuries is relatively low, the high proportion of these accidents involving
      paediatric patients and alcohol is of concern.

PMID- 26219187
TI  - [A history of men's health--on the origin of a field of research].
AB  - This contribution traces the conditions surrounding the emergence and development
      of a new field of research since the millennium. It primarily presents research
      initiated by the Stuttgart Institute for the History of Medicine: starting with
      the (re)discovery of sources and the setting up of bodies of sources for a gender
      sensitive, patient-oriented history of health (autobiographies, diaries,
      correspondence) it moves to issues such as health lifestyles, workers'
      masculinity, the use of medical services, health experiences during particular
      stages of life such as childhood or youth, as well as prevention, healthcare,
      mental health and the gender gap in life expectancy. In conclusion the article
      discusses possible theoretical frameworks and perspectives.

PMID- 26219188
TI  - [Masculinity and Meat Consumption--Historical Approchaes to a Current Health
      Issue].
AB  - In current health debates meat is often discussed as a health risk.
      Statistically, men consume more meat than women. Therefore they often appear as
      an especially vulnerable risk group. Based on current discussions about an
      increased health risk for men because of an above-average consumption of meat,
      this paper outlines aspects of the historical development of the relationship
      between masculinity and meat consumption from the 19th to the 21st century and
      emphasizes the importance of cultural constructed gender expectations for the
      eating habits of many men.

PMID- 26219189
TI  - [Accident cause masculinity?--Gender-related issues of accident victims between
      prevention and coping in Kaiserreich and Weimarer Republik].
AB  - Occupational accidents in industrial workplaces are a specific health problem for
      man. Therefore it seems adequate to use masculinities as a category of research
      in this field. For the Kaiserreich and the Weimarer Republik it shows that male
      workers relating to their danger awareness and behavior, prevention, accident
      causes and coping strategies are settled in an area of conflict between a hard
      workplace environment and the family. On the basis of health practices of the
      accident victims it appears that there are different forms of labor
      masculinities. They have an important influence on all levels of an occupational
      accident from the endangerment to the success of the treatment. Through a
      critical use of the category academic void can be shown and alternative
      explanatory models can be offered.

PMID- 26219190
TI  - [Migrants' masculinity and health. Taking care for one's health and coping with
      sickness of German migrants in the US in 19th and early 20th centuries].
AB  - In 19. and early 20. centuries several million emigrants from German speaking
      countries entered the United States of America. How migrants coped with sickness,
      how they preserved their health and to which ressources and institutions of help
      they had access is yet an academic void. Using Ego-documents--letters,
      autobiographic texts and diaries--of near-illiterate men this paper will analyse
      'healthy lifestyles' and practices of coping with sickness and contrast them with
      recent research findings in the field of 'mens' health'. Thereby the recent
      concept of ,male health-idiots' will be challenged in historical perspective.

PMID- 26219191
TI  - [Men in the history of nursing].
AB  - In German historiography the history of men in nursing is still a desideratum.
      While for female nurses considerable research has been done, the historiographic
      gaps in men's nursing comprise many periods and almost all subjects. The article
      concentrates on desiderata in the German historiography of nursing and shows
      after presenting a survey of the research literature, topics and research
      questions as well as sources which have not been analyzed yet. However, the
      history of female nursing is partly quite well investigated. This gives the
      opportunity for comparative analyzes. As since the middle of the 19th century
      nursing is perceived as a female occupation an examination of men in this area
      can help to sharpen the gender perspective.

PMID- 26219192
TI  - ["Should the staff's attitude towards the patients remain unchanged, I will not
      guarantee anything." Protest masculinity and coping of "rebellious patients" at
      the Heidelberg University Psychiatric Hospital on the eve of
      deinstitutionalization].
AB  - This article analyses the illness experiences of male patients from the
      Heidelberg University Psychiatric Hospital during the protests against Psychiatry
      in the year 1973. Protest is one of the most important expressions of masculinity
      in socially disadvantaged men, such as men with mental disorders. The analysis of
      100 medical records shows that some patients tried to construct themselves as men
      in a way that was explicitly motivated by antipsychiatric ideas: They questioned
      psychiatric authority, behaved "sexually inappropriate", or used drugs. On the
      eve of psychiatric reform in West Germany those patients were well aware that the
      alternative--complying with the treatment--would put them at considerable risk.
      In addition to the usual inference of hegemonic or normative masculinities as
      risk-factors, the behavior of those ,,rebellious patients" has to be interpreted
      as individual coping strategies.

PMID- 26219193
TI  - [Health Education for Men by the Federal Centre of Health Education: A
      Contribution to the Presentation of Men as unaware of Health? (1970-1990)].
AB  - This article offers a close consideration about the gender-specific contents of
      health education campaigns in the Federal Republic of Germany from 1970 to 1990.
      By using educational publications issued by the Bundeszentrale fur
      gesundheitliche Aufklarung (BZgA), it is shown which breaks and continuities
      emerged and which kinds of role models are thereby conveyed. Whereas the health
      education of the 1950s and 1960s was characterised by a didactical approach
      towards men and women, this changed as from the 1970s. By deconstructing
      exemplary education campaigns and including internal files of the BZgA, it can be
      shown, that the societal discourse on the feminism in the FRG contributed to the
      fact, that during the 1970s the switch has been made to an increased use of
      positive role models. However, within the men-specific health education there was
      no break; the health deficiency discourse was still applied in many and diverse
      ways in order to describe male health behaviour and knowledge.

PMID- 26219194
TI  - ["But there are also men!" Gender-specific health education and prevention in the
      GDR from the 1950th to the 1970th].
AB  - The notions of femininity and masculinity in the GDR health propaganda and their
      effects on the health consciousness and behaviour of the population in the GDR
      are the key topics of this article. The main questions of the first part are, if
      women and men were equally represented in educational materials and had to fulfil
      the same norms and expectations. The second part deals with ego-documents,
      primarily petitions to the Ministry of Health, as well as reports and evaluations
      from the local health authorities that shall help to answer the questions of male
      and female health behaviour. Additionally they can provide an insight into the
      views and actions of patients. Other factors such as the educational level,
      matters of milieu and regional peculiarities that have impact on the health
      status and behaviour will be discussed at the end of the article.

PMID- 26219195
TI  - Effects of curcumin on crevicular levels of IL-1beta and CCL28 in experimental
      gingivitis.
AB  - BACKGROUND: Curcumin has anti-inflammatory properties. The aim of this study was
      to compare interleukin-1beta (IL-1beta) and chemokine (C-C motif) ligand 28
      (CCL28) levels following a topical application of curcumin (CRM), chlorhexidine
      (CHX) and chlorhexidine-metronidazole (CHX-MTZ) in an experimental gingivitis
      human model. METHODS: Sixty systemically healthy selected subjects were randomly
      assigned to one of three topical antigingivitis gels. Each gel was applied twice
      daily for 10 minutes as the sole method of oral hygiene for 29 days on the test
      quadrant only. Modified gingival index (MGI), plaque index (PI), bleeding on
      probing (BOP) and probing depth (PD) were assessed at baseline, 29 days and 60
      days. Estimation of IL-1beta and CCL28 levels in gingival crevicular fluid was
      done at baseline and at 29 days. RESULTS: The increase of IL-1beta in the CRM
      (14.52 +/- 16.6 pg/ml) and CHX-MTZ (31.63 +/- 15.96) groups was significantly
      less than that of the CHX group (70.55 +/- 38.81). Similar results were also
      observed for CCL28 (CRM: 8.12 +/- 8.78 pg/ml; CHX-MTZ: 12.81 +/- 18.68; CHX:
      41.15 +/- 22.82). All groups had a significant increase in MGI, PI and BOP at 29
      days. CONCLUSIONS: The anti-inflammatory potential of topical curcumin was
      similar to CHX-MTZ but superior to CHX in affecting IL-1beta and CCL28 levels.

PMID- 26219196
TI  - Evaluation of prolonged epidural chloroprocaine for postoperative analgesia in
      infants.
AB  - STUDY OBJECTIVE: To describe the use and adverse effects of chloroprocaine for
      epidural analgesia in young infants for infusion durations greater than 3.5
      hours. DESIGN: A retrospective cohort review of the electronic medical record
      over a 14-month period. SETTING: The level IV neonatal intensive care unit of a
      414-bed free-standing children's hospital. PATIENTS: Eighteen infants (mean age,
      1.7 +/- 1.8 months [0.03-6.3]; mean weight, 3.8 +/- 1.3 kg [1.56-6.9]; n = 10
      [55%] males) received 1% chloroprocaine for epidural analgesia postoperatively
      for up to 96-hour duration and met criteria for inclusion. MEASUREMENTS: Dosing
      requirements, placement of epidural catheter, supplementary analgesic therapy,
      respiratory support, vital signs, and incidence of adverse events associated with
      local anesthetics were collected. MAIN RESULTS: Epidural catheter placement was
      caudal (n = 8), lumbar (n = 6), or thoracic (n = 4). Mean operative time was 2.48
      +/- 1 hour (1-5). Initial chloroprocaine dose was 1.3 +/- 0.5 mL/h (0.4-2.5) (3.5
      +/- 1 mg/kg per hour [1.4-5]) with a maximum dose of 1.5 +/- 0.6 mL/h (0.4-3)
      (4.2 +/- 1.1 mg/kg per hour [2.2-6.1]). Duration of epidural analgesia was 48.3
      +/- 21.5 hours (10-96). Duration of epidural infusion did not influence dosing
      requirement, suggesting the absence of drug tachyphylaxis. All patients received
      intermittent doses of opioid and nonopioid pain medications while receiving
      chloroprocaine. Two mechanically ventilated patients required continuous infusion
      of opioids. No adverse events were directly attributed to chloroprocaine use.
      CONCLUSION: Epidural 1% chloroprocaine, in doses of 0.4-3 mL/h (1.5-6.1 mg/kg per
      hour), was well tolerated in both mechanically ventilated and spontaneously
      breathing infants for up to 96 hours with no identified adverse effects or
      tachyphylaxis.

PMID- 26219198
TI  - The Quality of Nurses' Work Environment and Workforce Outcomes From the
      Perspective of Swiss Allied Healthcare Assistants and Registered Nurses: A Cross
      Sectional Survey.
AB  - BACKGROUND: Anticipating nursing shortages, the Swiss healthcare system recently
      introduced the position of allied healthcare assistant (AHA). However, indicators
      of AHAs' integration and stability, particularly their perceptions of their work
      environment quality and related outcomes (i.e., burnout, job satisfaction, and
      intention to leave), remain unclear. AIMS: (a) To describe AHAs' ratings of the
      quality of the nurse work environment, job satisfaction, burnout, and intention
      to leave their workplaces; (b) to compare AHAs' and registered nurses' (RNs')
      work environment quality ratings and related outcomes; and (c) to assess links
      between AHAs' work environment quality ratings and related workforce outcomes.
      DESIGN: A secondary analysis of RN4CAST data (October 2009 to June 2010) on 61
      AHAs and 466 RNs in 13 Swiss acute care hospitals. METHODS: We used descriptive
      statistics to summarize data of AHAs and RNs on their units and hospitals. Via
      binary logistic regression models, we compared AHAs and RNs and identified
      associations between work environment ratings and workforce outcomes. FINDINGS:
      AHAs' work environment quality ratings were significantly higher than those of
      RNs, and were associated with lower odds of burnout and intention to leave their
      current job and higher odds of reported job satisfaction. CONCLUSIONS: This study
      provides primary evidence linking AHAs' work environment quality ratings to
      burnout, job satisfaction, and intention to leave in acute care hospitals.
      CLINICAL RELEVANCE: Given the increasing importance of AHAs for nursing care
      provision, hospitals should assess the quality of nurse work environment and
      nurse outcomes from the perspective of all nurses.

PMID- 26219197
TI  - Legal Protections in Public Accommodations Settings: A Critical Public Health
      Issue for Transgender and Gender-Nonconforming People.
AB  - POLICY POINTS: Since 2012, Massachusetts law has provided legal protections
      against discrimination on the basis of gender identity in employment, housing,
      credit, public education, and hate crimes. The law does not protect against
      discrimination based on gender identity in public accommodations settings such as
      transportation, retail stores, restaurants, health care facilities, and
      bathrooms. A 2013 survey of Massachusetts transgender and other gender minority
      adults found that in the past 12 months, 65% had experienced public
      accommodations discrimination since the law was passed. This discrimination was
      associated with a greater risk of adverse emotional and physical symptoms in the
      past 30 days. Nondiscrimination laws inclusive of gender identity should protect
      against discrimination in public accommodations settings to support transgender
      people's health and their ability to access health care. CONTEXT: Gender minority
      people who are transgender or gender nonconforming experience widespread
      discrimination and health inequities. Since 2012, Massachusetts law has provided
      protections against discrimination on the basis of gender identity in employment,
      housing, credit, public education, and hate crimes. The law does not, however,
      protect against discrimination in public accommodations (eg, hospitals, health
      centers, transportation, nursing homes, supermarkets, retail establishments). For
      this article, we examined the frequency and health correlates of public
      accommodations discrimination among gender minority adults in Massachusetts, with
      attention to discrimination in health care settings. METHODS: In 2013, we
      recruited a community-based sample (n = 452) both online and in person. The
      respondents completed a 1-time, electronic survey assessing demographics, health,
      health care utilization, and discrimination in public accommodations venues in
      the past 12 months. Using adjusted multivariable logistic regression models, we
      examined whether experiencing public accommodations discrimination in health care
      was independently associated with adverse self-reported health, adjusting for
      discrimination in other public accommodations settings. FINDINGS: Overall, 65% of
      respondents reported public accommodations discrimination in the past 12 months.
      The 5 most prevalent discrimination settings were transportation (36%), retail
      (28%), restaurants (26%), public gatherings (25%), and health care (24%). Public
      accommodations discrimination in the past 12 months in health care settings was
      independently associated with a 31% to 81% increased risk of adverse emotional
      and physical symptoms and a 2-fold to 3-fold increased risk of postponement of
      needed care when sick or injured and of preventive or routine health care,
      adjusting for discrimination in other public accommodations settings (which also
      conferred an additional 20% to 77% risk per discrimination setting endorsed).
      CONCLUSIONS: Discrimination in public accommodations is common and is associated
      with adverse health outcomes among transgender and gender-nonconforming adults in
      Massachusetts. Discrimination in health care settings creates a unique health
      risk for gender minority people. The passage and enforcement of transgender
      rights laws that include protections against discrimination in public
      accommodations-inclusive of health care-are a public health policy approach
      critically needed to address transgender health inequities.

PMID- 26219200
TI  - Yes I can: Expected success promotes actual success in emotion regulation.
AB  - People who expect to be successful in regulating their emotions tend to
      experience less frequent negative emotions and are less likely to suffer from
      depression. It is not clear, however, whether beliefs about the likelihood of
      success in emotion regulation can shape actual emotion regulation success. To
      test this possibility, we manipulated participants' beliefs about the likelihood
      of success in emotion regulation and assessed their subsequent ability to
      regulate their emotions during a negative emotion induction. We found that
      participants who were led to expect emotion regulation to be more successful were
      subsequently more successful in regulating their emotional responses, compared to
      participants in the control condition. Our findings demonstrate that expected
      success can contribute to actual success in emotion regulation.

PMID- 26219199
TI  - Nonclinical safety testing of biopharmaceuticals--Addressing current challenges
      of these novel and emerging therapies.
AB  - Non-clinical safety testing of biopharmaceuticals can present significant
      challenges to human risk assessment with these often innovative and complex
      drugs. Hot Topics in this field were discussed recently at the 4th Annual
      European Biosafe General Membership meeting. In this feature article, the
      presentations and subsequent discussions from the main sessions are summarized.
      The topics covered include: (i) wanted versus unwanted immune activation, (ii) bi
      specific protein scaffolds, (iii) use of Pharmacokinetic (PK)/Pharmacodynamic
      (PD) data to impact/optimize toxicology study design, (iv) cytokine release and
      challenges to human translation (v) safety testing of cell and gene therapies
      including chimeric antigen receptor T (CAR-T) cells and retroviral vectors and
      (vi) biopharmaceutical development strategies encompassing a range of diverse
      topics including optimizing entry of monoclonal antibodies (mAbs) into the brain,
      safety testing of therapeutic vaccines, non-clinical testing of biosimilars,
      infection in toxicology studies with immunomodulators and challenges to human
      risk assessment, maternal and infant anti-drug antibody (ADA) development and
      impact in non-human primate (NHP) developmental toxicity studies, and a summary
      of an NC3Rs workshop on the future vision for non-clinical safety assessment of
      biopharmaceuticals. 

PMID- 26219201
TI  - Identification and disruption of bacteria associated with sheep scab mites-novel
      means of control?
AB  - Psoroptes ovis mites, which cause psoroptic mange (sheep scab), were investigated
      to identify potential bacterial targets for endosymbiont control of sheep scab.
      In addition, transmission of bacteria to the sheep skin was investigated through
      the characterisation of bacteria present in P. ovis faecal trails and on the
      fleece environment by internal transcribed spacer (ITS) sequencing. A diverse
      range of bacteria was identified in addition to a potential endosymbiont
      candidate, Comamonas sp, which was detected in P. ovis by both ITS PCR and
      endosymbiont-specific PCR. Disruption of these bacteria within P. ovis, through
      the use of antibiotics, was explored; with significant reduction in mean mite
      survival when administered antibiotic diets compared with controls (LR4 = 23.12,
      P < 0.001). The antibiotic treatments also significantly affected the bacterial
      density (CFU/mite) within P. ovis, indicating that mite survival may be linked to
      the bacterial communities that they harbour. Although antibiotics are not
      suitable for practical application, these results suggest disrupting bacteria
      associated with P. ovis should be further investigated for novel control. 

PMID- 26219202
TI  - Immunoblotting using Strongyloides venezuelensis larvae, parthenogenetic females
      or eggs extracts for the diagnosis of experimentally infected immunosuppressed
      rats.
AB  - The nematode Strongyloides stercoralis is responsible for strongyloidiasis in
      humans. Diagnosis of infection occurs through detection of larvae in feces, but
      low elimination of larvae often hampers the detection of disease, particularly in
      cases of patient immunosuppression. Immunodiagnostic tests have been developed;
      however obtaining S. stercoralis larvae for the production of homologous antigen
      extract is technically difficult. Thus, the use different developmental forms of
      Strongyloides venezuelensis has become an alternative method for the production
      of antigen extracts. The aim of this study was to evaluate immunoblotting using
      alkaline extracts from S. venezuelensis L3 larvae, parthenogenetic females or
      eggs to test detection of experimental strongyloidiasis associated with
      immunosuppression. Immunocompetent and immunosuppressed male rats were
      experimentally infected, and serum sample from all animals were obtained at 0, 5,
      8 13, and 21 days post infection (d.p.i.). Immunoblotting was evaluated for use
      in detection of anti-S. venezuelensis IgG in both experimental rat groups. The
      larval extract immunoblotting profile had the most immunoreactive fractions in
      the immunosuppressed group beginning at 5 d.p.i., while the immunocompetent group
      reactivity began on 8 d.p.i. Immunoreactive protein fractions of 17 kDa present
      in larval alkaline extract presented as possible markers of infection in
      immunosuppressed rats. It is concluded that all extracts using immunoblotting
      have diagnostic potential in experimental strongyloidiasis, particularly larval
      extract in immunosuppressed individuals. 

PMID- 26219203
TI  - The proliferation potential of promastigotes of the main Leishmania species of
      the old world in NNN culture medium prepared using blood of four different
      mammals.
AB  - The efficacy of the in vitro cultivation of promastigotes of four Leishmania spp.
      was tested in the biphasic Novy-MacNeal-Nicolle (NNN) medium prepared using blood
      from different animals (horse, donkey, goat and sheep). The aim was to test which
      NNN preparation gave the best yield in the shortest time for different parasite
      species, in order to obtain a large crop of promastigotes for experimental work
      and for antigen preparation. Promastigotes of Leishmania infantum, Leishmania
      donovani, Leishmania tropica and Leishmania major, the four main parasite species
      occurring in the old world, were defrosted from -80  degrees C and placed, at
      equal numbers, in the 4 different NNN preparations. At the end of the 7th day,
      the NNN medium using horse blood produced the greatest number of promastigotes
      for all Leishmania spp. tested, whilst goat blood proved the poorest medium,
      providing culture results only for L. infantum. This finding may be explained by
      the fact that Leishmania is a nicotinamide adenine dinucleotide (NAD) auxotroph
      and horse erythrocytes support NAD-dependent microorganisms. 

PMID- 26219204
TI  - Safety of PEGylated recombinant human full-length coagulation factor VIII (BAX
      855) in the overall context of PEG and PEG conjugates.
AB  - INTRODUCTION: BAX 855 is a PEGylated human full-length recombinant factor VIII
      (rFVIII) based on licensed rFVIII (ADVATE). The applied PEGylation technology has
      been optimized to retain functionality of the FVIII molecule, improve its
      pharmacokinetic properties and allow less frequent injections while maintaining
      efficacy. AIM: The aim of this study was to confirm that the excellent safety
      profile of ADVATE remains unchanged after PEGylation. METHODS: Non-clinical
      safety studies with BAX 855 and its respective unbound polyethylene glycol (PEG)
      were conducted in several species. The distribution of a single dose of
      radiolabelled BAX 855 was further investigated in rats. Publically available
      safety data on PEG alone and PEGylated biomolecules were summarized and reviewed
      for specific safety findings attributable to PEG or PEGylated biopharmaceuticals.
      RESULTS: Safety pharmacology studies in rabbits and macaques and repeated dose
      toxicity studies in rats and macaques identified no safety issues. Results of a
      distribution study in rats administered radiolabelled BAX 855 showed that
      radioactivity was completely excreted; urine was the major elimination route. A
      28-day study in rats dosed with the unbound PEG constituent (PEG2ru20KCOOH) of
      BAX 855 showed no adverse or non-adverse effects. Safety data for PEG and PEG
      protein conjugates indicate no safety concerns associated with PEG at clinically
      relevant dose levels. Although vacuolation of certain cell types has been
      reported in mammals, no such vacuolation was observed with BAX 855 or with the
      unbound PEG constituent. CONCLUSION: Non-clinical safety evaluation of PEG and
      BAX 855 identified no safety signals; the compound is now in clinical development
      for the treatment of patients with haemophilia A.

PMID- 26219205
TI  - Human mesenchymal stromal cells decrease mortality after intestinal ischemia and
      reperfusion injury.
AB  - BACKGROUND: Cellular therapy is a novel treatment option for intestinal ischemia.
      Bone marrow-derived mesenchymal stromal cells (BMSCs) have previously been shown
      to abate the damage caused by intestinal ischemia/reperfusion (I/R) injury. We
      therefore hypothesized that (1) human BMSCs (hBMSCs) would produce more
      beneficial growth factors and lower levels of proinflammatory mediators compared
      to differentiated cells, (2) direct application of hBMSCs to ischemic intestine
      would decrease mortality after injury, and (3) decreased mortality would be
      associated with an altered intestinal and hepatic inflammatory response. METHODS:
      Adult hBMSCs and keratinocytes were cultured on polystyrene flasks. For in vitro
      experiments, cells were exposed to tumor necrosis factor, lipopolysaccharides, or
      2% oxygen for 24 h. Supernatants were then analyzed for growth factors and
      chemokines by multiplex assay. For in vivo experiments, 8- to 12-wk-old male
      C57Bl6J mice were anesthetized and underwent a midline laparotomy. Experimental
      groups were exposed to temporary superior mesenteric artery occlusion for 60 min.
      Immediately after ischemia, 2 * 10(6) hBMSCs or keratinocytes in phosphate
      buffered saline were placed into the peritoneal cavity. Animals were then closed
      and allowed to recover for 6 h (molecular/histologic analysis) or 7 d (survival
      analysis). After 6-h reperfusion, animals were euthanized. Intestines and livers
      were harvested and analyzed for inflammatory chemokines, growth factors, and
      histologic changes. RESULTS: hBMSCs expressed higher levels of human interleukin
      (IL) 6, IL-8, vascular endothelial growth factor (VEGF), and epidermal growth
      factor and lower levels of IL-1, IL-3, IL-7, and granulocyte-monocyte colony
      stimulating factor after stimulation. In vivo, I/R resulted in significant
      mortality (70% mortality), whereas application of hBMSCs after ischemia decreased
      mortality to 10% in a dose-dependent fashion (P = 0.004). Keratinocyte therapy
      offered no improvements in mortality above I/R. Histologic profiles were
      equivalent between ischemic groups, regardless of the application of hBMSCs or
      keratinocytes. Cellular therapy yielded significantly decreased murine intestinal
      levels of soluble activin receptor-like kinase 1, betacellulin, and endothelin,
      whereas increasing levels of eotaxin, monokine induced by gamma interferon (MIG),
      monocyte chemoattractant protein 1, IL-6, granulocyte colony-stimulating factor
      (G-CSF), and interferon gamma-induced protein 10 (IP-10) from ischemia were
      appreciated. hBMSC therapy yielded significantly higher expression of murine
      intestinal VEGF and lower levels of intestinal MIG compared to keratinocyte
      therapy. Application of hBMSCs after ischemia yielded significantly lower murine
      levels of hepatic MIG, IP-10, and G-CSF compared to keratinocyte therapy.
      CONCLUSIONS: Human BMSCs produce multiple beneficial growth factors. Direct
      application of hBMSCs to the peritoneal cavity after intestinal I/R decreased
      mortality by 60%. Improved outcomes with hBMSC therapy were not associated with
      improved histologic profiles in this model. hBMSC therapy was associated with
      higher VEGF in intestines and lower levels of proinflammtory MIG, IP-10, and G
      CSF in liver tissue after ischemia, suggesting that reperfusion with hBMSC
      therapy may alter survival by modulating the systemic inflammatory response to
      ischemia.

PMID- 26219206
TI  - TiProtec preserves endothelial function in a rat model.
AB  - BACKGROUND: Coronary artery bypass surgery provides excellent patency rates;
      however, the early and/or late graft failure reduces the long-term benefit of
      myocardial revascularization. We investigated the effectiveness of generally used
      saline, Custodiol solutions and a new solution (TiProtec) at preserving
      endothelium after cold ischemia and warm reperfusion injury. MATERIALS AND
      METHODS: Aortic transplantations were performed in Lewis rats. Aortic arches were
      stored in saline, Custodiol, and TiProtec solutions for 2 h then were
      transplanted into the abdominal aorta. Two, 24 hours and 1 week after
      transplantation, the implanted grafts were harvested. Endothelium-dependent and 
      independent vasorelaxations were investigated in organ bath. DNA strand breaks
      were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling-method, messenger RNA expressions by quantitative real-time polymerase
      chain reaction, and the expression of CD-31 and alpha smooth muscle actin by
      immunochemistry. RESULTS: Severely impaired endothelial function and integrity of
      implanted aortic grafts were shown after 2 h in the saline, Custodiol group
      (maximal vasorelaxation to acetylcholine: control: 91 +/- 2%, saline: 26 +/- 5%,
      Custodiol: 24 +/- 5%, CD-31-positive area control: 96 +/- 2%, saline: 35 +/- 13%
      Custodiol: 54 +/- 5%, P < 0.05, respectively); however, a preserved endothelial
      function was observed in the TiProtec group when compared with the saline and
      Custodiol group (maximal vasorelaxation: 46 +/- 7%, CD-31-positive area: 54 +/-
      10%, P < 0.05). After 1 wk, endothelial function was partially recovered in all
      groups; however, it was significantly better in the TiProtec group (maximal
      vasorelaxation to acetylcholine: saline: 42 +/- 3%, Custodiol: 48 +/- 3%,
      TiProtec: 56 +/- 3%, CD-31-positive area: saline: 56 +/- 5%, Custodiol: 54 +/-
      4%; TiProtec: 83 +/- 6%, P < 0.05, respectively). In addition, messenger RNA
      levels of Bax, B-cell lymphoma-2, endothelial NOS, vascular endothelial growth
      factor 2, and caspase-3 were significantly altered in both groups. CONCLUSIONS:
      TiProtec appears to be superior for the preservation of endothelial- and smooth
      muscle cells of bypass graft after cold storage and warm reperfusion in our
      murine model.

PMID- 26219207
TI  - Sexuality and fertility outcomes after hand sewn versus stapled ileal pouch anal
      anastomosis for ulcerative colitis.
AB  - BACKGROUND: Ileal pouch anal anastomosis (IPAA) may alter sexuality and fertility
      in women. The laparoscopic approach seems to reduce infertility rates in women
      after IPAA. However, the impact of hand sewn versus stapled IPAA on sexuality and
      fertility has never been assessed in patients with ulcerative colitis (UC). The
      objective of this study was to analyze the impact of the IPAA technique on
      sexuality and fertility in UC. METHODS: All UC patients who underwent an IPAA
      between May 1996 and April 2011 were included. The patients answered mailed
      questionnaires including sexuality validated questionnaires and fertility
      questionnaires. The risk factors of sexual dysfunction were explored. RESULTS: A
      total of 135 patients were included. Eighty-eight patients (65%) answered the
      questionnaires. Their mean age and follow-up were 37.2 +/- 13.4 y and 109.7 +/-
      57.5 mo. The rates of female and male sexual dysfunction were 50% and 29%,
      respectively. Intestinal transit disorders were identified as risk factors in
      both men and women and anastomotic stricture in women sexual dysfunction, in
      univariate analyses. The IPAA technique did not impact sexual function in women
      but there was a trend for less erectile dysfunction after hand sewn IPAA (16.7%
      versus 44.4%). The fertility rate was 47% in women and 75% in men, with a trend
      for a better fertility in women after hand sewn IPAA (P = 0.07). CONCLUSIONS: In
      this preliminary study, the hand sewn or stapled IPAA technique did not impact
      the sexuality or fertility outcomes of UC patients, but there was a trend for
      better female fertility and male erectile function after hand sewn IPAA.
      Intestinal transit disorders contributed to male and female sexual dysfunction
      after IPAA.

PMID- 26219208
TI  - Lysis of mid-uterine central adhesions has lower recurrence risk.

PMID- 26219212
TI  - Inferences About Sexual Orientation: The Roles of Stereotypes, Faces, and The
      Gaydar Myth.
AB  - In the present work, we investigated the pop cultural idea that people have a
      sixth sense, called "gaydar," to detect who is gay. We propose that "gaydar" is
      an alternate label for using stereotypes to infer orientation (e.g., inferring
      that fashionable men are gay). Another account, however, argues that people
      possess a facial perception process that enables them to identify sexual
      orientation from facial structure. We report five experiments testing these
      accounts. Participants made gay-or-straight judgments about fictional targets
      that were constructed using experimentally manipulated stereotypic cues and real
      gay/straight people's face cues. These studies revealed that orientation is not
      visible from the face-purportedly "face-based" gaydar arises from a third
      variable confound. People do, however, readily infer orientation from stereotypic
      attributes (e.g., fashion, career). Furthermore, the folk concept of gaydar
      serves as a legitimizing myth: Compared to a control group, people stereotyped
      more often when led to believe in gaydar, whereas people stereotyped less when
      told gaydar is an alternate label for stereotyping. Discussion focuses on the
      implications of the gaydar myth and why, contrary to some prior claims,
      stereotyping is highly unlikely to result in accurate judgments about
      orientation. 

PMID- 26219213
TI  - Exposure to nicotine increases dopamine receptor content in the mesocorticolimbic
      pathway of rat dams and offspring during lactation.
AB  - Nicotine exposure causes the release of dopamine from the ventral tegmental area
      (VTA) to the nucleus accumbens (NAc). We have previously shown that maternal
      exposure to nicotine during lactation causes hyperleptinemia in dams and pups,
      and leptin is known to decrease dopamine release from the VTA. Here we evaluated
      whether maternal exposure to nicotine during lactation causes changes in dopamine
      and leptin signaling pathways at the end of exposure and after 5days of
      withdrawal in the: VTA, NAc, arcuate nucleus (ARC) and dorsal striatum (DS). On
      postnatal day (PN) 2, lactating Wistar rats were implanted with minipumps
      releasing nicotine (NIC; 6mg/kg/day, s.c.) or saline (C) for 14days. Offspring
      were tested in the elevated plus maze (EPM) and open field on PN14 or PN20, and
      euthanized on PN15 or PN21. Entries into the open arms and head dips in the EPM
      were reduced in NIC pups at P20. At weaning (PN21), NIC dams had: lower tyrosine
      hydroxylase (TH), higher OBRb and SOCS3 contents in VTA; lower TH, higher D1R,
      D2R and DAT contents in NAc; higher TH content in DS; and higher D2R and SOCS3
      contents in ARC. On PN15, NIC offspring had higher D1R, D2R and lower DAT
      contents in NAc, while on PN21, they had lower DAT in DS, and lower pSTAT3
      content in ARC. We evidenced that postnatal nicotine exposure induces relevant
      changes in the brain reward system of dams and pups, possibly associated with
      changes in leptinemia and increased offspring anxiety-like behavior. 

PMID- 26219214
TI  - Lessons from Fraxinus, a crowd-sourced citizen science game in genomics.
AB  - In 2013, in response to an epidemic of ash dieback disease in England the
      previous year, we launched a Facebook-based game called Fraxinus to enable non
      scientists to contribute to genomics studies of the pathogen that causes the
      disease and the ash trees that are devastated by it. Over a period of 51 weeks
      players were able to match computational alignments of genetic sequences in 78%
      of cases, and to improve them in 15% of cases. We also found that most players
      were only transiently interested in the game, and that the majority of the work
      done was performed by a small group of dedicated players. Based on our
      experiences we have built a linear model for the length of time that contributors
      are likely to donate to a crowd-sourced citizen science project. This model could
      serve a guide for the design and implementation of future crowd-sourced citizen
      science initiatives. 

PMID- 26219215
TI  - The prevalence of enterotoxin and antibiotic resistance genes in clinical and
      intestinal Bacteroides fragilis group isolates in Turkey.
AB  - This study was conducted to measure the antibiotic susceptibilities,
      corresponding gene contents, and the enterotoxin gene bft, in 50 Bacteroides
      fragilis group isolates, 25 of which were clinical and 25 intestinal. The
      resistance rates to amoxicillin/clavulanic acid, imipenem and metronidazole were
      low; ampicillin and tetracyclin resistance was high; clindamycin resistance and
      ermF gene presence was also high. Regarding phenotypical bacterial resistance and
      the presence of resistance genes, there was not statistically significant
      difference between clinical and intestinal isolates and bft positive and negative
      isolates. 

PMID- 26219216
TI  - Regulation of growth rate and developmental timing by Xenopus thyroid hormone
      receptor alpha.
AB  - Thyroid hormone (TH) is critical for vertebrate postembryonic development, a
      period around birth in mammals when plasma TH levels are high. Interestingly, TH
      receptors (TRs), especially TRalpha, are expressed prior to the synthesis and
      secretion of zygotic TH, suggesting the existence of unliganded TR during
      development. However, the role of unliganded TR during mammalian development has
      been difficult to study, in part due to the relatively weak phenotype of TR
      knockout mice. Amphibian metamorphosis resembles postembryonic development in
      mammals and is controlled by TH via TRs. Like in mammals, TRalpha gene is highly
      activated and is the major TR expressed prior to the synthesis of endogenous TH.
      By using TALEN (transcriptional activator like effector nucleases)-mediated gene
      editing approach, we and others have now shown that unliganded TRalpha has two
      independent functions during Xenopus premetamorphosis, i.e. inhibiting growth
      rate and slowing development. Furthermore, molecular and transgenic studies have
      shown that unliganded TRalpha accomplishes these via the recruitment of histone
      deacetylase (HDAC)-containing corepressor complexes to repress the expression of
      TH-inducible genes. 

PMID- 26219217
TI  - Towards a tunable graphene-based Landau level laser in the terahertz regime.
AB  - Terahertz (THz) technology has attracted enormous interest with conceivable
      applications ranging from basic science to advanced technology. One of the main
      challenges remains the realization of a well controlled and easily tunable THz
      source. Here, we predict the occurrence of a long-lived population inversion in
      Landau-quantized graphene (i.e. graphene in an external magnetic field)
      suggesting the design of tunable THz Landau level lasers. The unconventional non
      equidistant quantization in graphene offers optimal conditions to overcome the
      counteracting Coulomb- and phonon-assisted scattering channels. In addition to
      the tunability of the laser frequency, we show that also the polarization of the
      emitted light can be controlled. Based on our microscopic insights into the
      underlying many-particle mechanisms, we propose two different experimentally
      realizable schemes to design tunable graphene-based THz Landau level lasers. 

PMID- 26219218
TI  - Double-Stereodifferentiation in Rhodium-Catalyzed [2 + 2 + 2] Cycloaddition:
      Chiral Ligand/Chiral Counterion Matched Pair.
AB  - The first enantioselective metal-catalyzed [2 + 2 + 2] cycloaddition involving a
      double asymmetric induction has been devised. It relies on the use of an in situ
      generated chiral cationic rhodium(I) catalyst with a matched chiral ligand/chiral
      counterion pair. Careful optimization of the catalytic system, as well as of the
      reaction conditions, led to atroposelective [2 + 2 + 2] pyridone cycloadducts
      with high ee's up to 96%. This strategy outperformed those previously described
      involving a chiral ligand only or a chiral counterion only. 

PMID- 26219219
TI  - Reactive modeling of the initial stages of alkoxysilane polycondensation: effects
      of precursor molecule structure and solution composition.
AB  - Reactive molecular dynamics simulations were performed to study the
      polycondensation of alkoxysilane in solution with alcohol and water. The dynamic
      formation of siloxane clusters and rings was observed with simulation time. Two
      mechanisms for the growth of siloxanes were observed: monomer addition and
      cluster-cluster aggregation. The impacts of the alkoxysilane monomer chemical
      structure and solution composition on the rates of hydrolysis and condensation
      were explored. The polycondensation of different precursor alkoxysilane monomers
      (tetramethoxysilane, trimethoxysilane, methyltrimethoxysilane, or
      tetraethoxysilane) was modeled. The steric bulk of chemical groups attached to
      the monomer, such as silyl or alkoxy groups, were found to impact reaction rates.
      The influence of solution composition was investigated by simulating multiple
      systems with different concentrations of tetramethoxysilane, methanol, and water.
      Reactive molecular dynamics is used for the first time to study the
      polycondensation of alkoxysilanes, creating opportunities for future theoretical
      studies of the sol-gel process. 

PMID- 26219220
TI  - Determination of muscle mitochondrial respiratory capacity in Standardbred
      racehorses as an aid to predicting exertional rhabdomyolysis.
AB  - This prospective cohort study evaluated the potential of high-resolution
      respirometry applied to permeabilized muscle fibers for fitness evaluation in
      French Standardbred racehorses. Fitness evaluation by means of respirometric
      parameters did not correlate with racing performance registered over the
      following racing season. However, altered mitochondrial energy metabolism was
      associated with higher risk of developing exertional rhabdomyolysis, a common
      cause of exercise intolerance in racehorses. These data represent a first step
      towards establishing reference values for muscle OXPHOS capacity in this breed. 

PMID- 26219221
TI  - Endogenous level of TIGAR in brain is associated with vulnerability of neurons to
      ischemic injury.
AB  - In previous studies, we showed that TP53-induced glycolysis and apoptosis
      regulator (TIGAR) protects neurons against ischemic brain injury. In the present
      study, we investigated the developmental changes of TIGAR level in mouse brain
      and the correlation of TIGAR expression with the vulnerability of neurons to
      ischemic injury. We found that the TIGAR level was high in the embryonic stage,
      dropped at birth, partially recovered in the early postnatal period, and then
      continued to decline to a lower level in early adult and aged mice. The TIGAR
      expression was higher after ischemia/reperfusion in mouse brain 8 and 12 weeks
      after birth. Four-week-old mice had smaller infarct volumes, lower neurological
      scores, and lower mortality rates after ischemia than 8- and 12-week-old mice.
      TIGAR expression also increased in response to oxygen glucose deprivation
      (OGD)/reoxygenation insult or H2O2 treatment in cultured primary neurons from
      different embryonic stages (E16 and E20). The neurons cultured from the early
      embryonic period had a greater resistance to OGD and oxidative insult. Higher
      TIGAR levels correlated with higher pentose phosphate pathway activity and less
      oxidative stress. Older mice and more mature neurons had more severe DNA and
      mitochondrial damage than younger mice and less mature neurons in response to
      ischemia/reperfusion or OGD/reoxygenation insult. Supplementation of cultured
      neurons with nicotinamide adenine dinuclectide phosphate (NADPH) significantly
      reduced ischemic injury. These results suggest that TIGAR expression changes
      during development and its expression level may be correlated with the
      vulnerability of neurons to ischemic injury. 

PMID- 26219209
TI  - Associations between Verbal Learning Slope and Neuroimaging Markers across the
      Cognitive Aging Spectrum.
AB  - A symptom of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a
      flat learning profile. Learning slope calculation methods vary, and the optimal
      method for capturing neuroanatomical changes associated with MCI and early AD
      pathology is unclear. This study cross-sectionally compared four different
      learning slope measures from the Rey Auditory Verbal Learning Test (simple slope,
      regression-based slope, two-slope method, peak slope) to structural neuroimaging
      markers of early AD neurodegeneration (hippocampal volume, cortical thickness in
      parahippocampal gyrus, precuneus, and lateral prefrontal cortex) across the
      cognitive aging spectrum [normal control (NC); (n=198; age=76+/-5), MCI (n=370;
      age=75+/-7), and AD (n=171; age=76+/-7)] in ADNI. Within diagnostic group,
      general linear models related slope methods individually to neuroimaging
      variables, adjusting for age, sex, education, and APOE4 status. Among MCI, better
      learning performance on simple slope, regression-based slope, and late slope
      (Trial 2-5) from the two-slope method related to larger parahippocampal thickness
      (all p-values<.01) and hippocampal volume (p<.01). Better regression-based slope
      (p<.01) and late slope (p<.01) were related to larger ventrolateral prefrontal
      cortex in MCI. No significant associations emerged between any slope and
      neuroimaging variables for NC (p-values >=.05) or AD (p-values >=.02). Better
      learning performances related to larger medial temporal lobe (i.e., hippocampal
      volume, parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in
      MCI only. Regression-based and late slope were most highly correlated with
      neuroimaging markers and explained more variance above and beyond other common
      memory indices, such as total learning. Simple slope may offer an acceptable
      alternative given its ease of calculation.

PMID- 26219222
TI  - Dysfunction of autophagy as the pathological mechanism of motor neuron disease
      based on a patient-specific disease model.
AB  - Autophagy is the main catabolic pathway in cells for the degradation of impaired
      proteins and organelles. Accumulating evidence supports the hypothesis that
      dysfunction of autophagy, leading to an imbalance of proteostasis and the
      accumulation of toxic proteins in neurons, is a central player in the
      pathogenesis of neurodegenerative diseases such as Alzheimer's disease,
      Parkinson's disease, and amyotrophic lateral sclerosis (ALS). The clinical
      pathology of ALS is complex and many genes associated with autophagy and RNA
      processing are mutated in patients with the familial form. But a causal
      relationship between autophagic dysfunction and ALS has not been fully
      established. More importantly, studies on the pathological mechanism of ALS are
      mainly based on animal models that may not precisely recapitulate the disease
      itself in human beings. The development of human iPSC techniques allows us to
      address these issues directly in human cell models that may profoundly influence
      drug discovery for ALS. 

PMID- 26219223
TI  - Regulation of autophagic flux by CHIP.
AB  - Autophagy is a major degradation system which processes substrates through the
      steps of autophagosome formation, autophagosome-lysosome fusion, and substrate
      degradation. Aberrant autophagic flux is present in many pathological conditions
      including neurodegeneration and tumors. CHIP/STUB1, an E3 ligase, plays an
      important role in neurodegeneration. In this study, we identified the regulation
      of autophagic flux by CHIP (carboxy-terminus of Hsc70-interacting protein).
      Knockdown of CHIP induced autophagosome formation through increasing the PTEN
      protein level and decreasing the AKT/mTOR activity as well as decreasing
      phosphorylation of ULK1 on Ser757. However, degradation of the autophagic
      substrate p62 was disturbed by knockdown of CHIP, suggesting an abnormality of
      autophagic flux. Furthermore, knockdown of CHIP increased the susceptibility of
      cells to autophagic cell death induced by bafilomycin A1. Thus, our data suggest
      that CHIP plays roles in the regulation of autophagic flux. 

PMID- 26219225
TI  - Prokaryotic microbiota in the digestive cavity of the jellyfish Cotylorhiza
      tuberculata.
AB  - The microbiota associated to the gastric cavity of four exemplars of the
      jellyfish Cotylorhiza tuberculata has been studied by means of cultured-dependent
      and -independent methods. The pyrosequencing approach rendered a very reduced
      diversity of Bacteria with four major groups shared by the four exemplars that
      made up to 95% of the total diversity. The culturing approach recovered low
      abundant organisms and some of them also detected by the pyrosequencing approach.
      The major key organisms were related to the genera Spiroplasma, Thalassospira,
      Tenacibaculum (from the pyrosequencing data), and Vibrio (from the cultivable
      fraction). Altogether the results indicate that C. tuberculata harbors an
      associated microbiota of very reduced diversity. On the other hand, some of the
      major key players may be potential pathogens and the host may serve as dispersal
      mechanism. 

PMID- 26219224
TI  - Regulation of mitophagy in ischemic brain injury.
AB  - The selective degradation of damaged or excessive mitochondria by autophagy is
      termed mitophagy. Mitophagy is crucial for mitochondrial quality control and has
      been implicated in several neurodegenerative disorders as well as in ischemic
      brain injury. Emerging evidence suggested that the role of mitophagy in cerebral
      ischemia may depend on different pathological processes. In particular, a
      neuroprotective role of mitophagy has been proposed, and the regulation of
      mitophagy seems to be important in cell survival. For these reasons, extensive
      investigations aimed to profile the mitophagy process and its underlying
      molecular mechanisms have been executed in recent years. In this review, we
      summarize the current knowledge regarding the mitophagy process and its role in
      cerebral ischemia, and focus on the pathological events and molecules that
      regulate mitophagy in ischemic brain injury. 

PMID- 26219226
TI  - [Dermatomyositis-update].
AB  - Dermatomyositis is a rare idiopathic inflammatory myopathy that affects adults
      and children, mostly female. Hallmarks of the disease are myositis with necrosis,
      regeneration and perifascicular atrophy accompanied by a typical skin rash with
      heliotrope erythema, Gottron's sign, Gottron's papules and nail fold changes with
      splinter hemorrhage. Typical skin symptoms may appear 6 months up to 2 years
      before muscle involvement (amyopathic dermatomyositis). New myositis-specific
      antibodies may allow clinicoserologic correlations within a heterogeneous
      clinical spectrum. Autoantibody profiles, subtype of myositis, overlap with other
      collagen vascular disorders and/or malignancy (paraneoplastic dermatomyositis) as
      well as age of the patients all have a considerable impact on course and
      prognosis. Infections, drugs and tumors may trigger activation of T and B cells,
      plasmacytoid dendritic cells, overproduction of type I interferons and complement
      mediated endothelial cell damage resulting in vasculopathy. UV radiation may also
      trigger dermatomyositis. Oral corticosteroids (1.5-2.0 mg/kg body weight/day) are
      the mainstay of treatment until improvement of muscle symptoms and/or
      normalization of muscle enzymes with subsequent slow tapering. Corticosteroids
      may be given as monotherapy or combined with steroid-sparing immunosuppressive
      agents' i.e. azathioprine, methotrexate, mycophenolate mofetil or high-dose
      intravenous immunoglobulins. Prognosis has improved considerably since use of
      high-dose corticosteroids, from 50 to 90% response rate. New therapies with
      biologicals (anti-CD20-, anti-TNFalpha-, anti-interferon antibodies) and Janus
      kinase inhibitors are currently being evaluated.

PMID- 26219227
TI  - Ion-ion interactions in beta-NaGdF4:Yb(3+),Er(3+) nanocrystals--the effect of ion
      concentration and their clustering.
AB  - In this work we report co-thermolysis as a suitable method for nanomaterial
      synthesis which allows the creation of hexagonal upconverting nanocrystals,
      NaGdF4:Yb(3+),Er(3+), in a wide range of sizes (20-120 nm). Only a very high
      Yb(3+) concentration (above 70%) results in pure cubic-phase nanocrystals with
      irregular shape. Additionally, we showed that the impact of Yb(3+), Er(3+) and
      Gd(3+) ions on the size and optical properties of nanocrystals is significant. We
      found that the main changes in optical properties do not depend on the
      nanocrystal size mostly, but are determined by the ion-ion interactions which
      include both Er(3+)-Er(3+) and Er(3+)-Yb(3+) cross relaxation. 

PMID- 26219228
TI  - Isoliensinine induces apoptosis in triple-negative human breast cancer cells
      through ROS generation and p38 MAPK/JNK activation.
AB  - Isoliensinine, liensinine and neferine are major bisbenzylisoquinoline alkaloids
      in the seed embryo of lotus (Nelumbo nucifera), and exhibit potential anti-cancer
      activity. Here, we explored the effects of these alkaloids on triple-negative
      breast cancer cells and found that among the three alkaloids isoliensinine
      possesses the most potent cytotoxic effect, primarily by inducing apoptosis.
      Interestingly, isoliensinine showed a much lower cytotoxicity against MCF-10A, a
      normal human breast epithelial cell line. Further studies showed that
      isoliensinine could significantly increase the production of reactive oxygen
      species (ROS) in triple-negative breast cancer cells, but not in MCF-10A cells.
      The isoliensinine-induced apoptosis could be attenuated by radical oxygen
      scavenger N-acetyl cysteine, suggesting that the cytotoxic effect of
      isoliensinine on cancer cells is at least partially achieved by inducing
      oxidative stress. We found that both p38 MAPK and JNK signaling pathways were
      activated by isoliensinine treatment and contributed to the induction of
      apoptosis. Furthermore, inhibitors or specific siRNAs of p38 MAPK and JNK could
      attenuate apoptosis induced by isoliensinine. However, only the p38 inhibitor or
      p38-specific siRNA blocked the elevation of ROS in isoliensinine-treated cells.
      Our findings thus revealed a novel antitumor effect of isoliensinine on breast
      cancer cells and may have therapeutic implications. 

PMID- 26219229
TI  - Survey of genetic diversity of IgG in wild and domestic rabbits.
AB  - We sequenced IgG from genomic DNA of 30 wild European rabbits of O. c. algirus
      and O. c. cuniculus subspecies from three regions and 15 domestic O. c.
      cuniculus. Genetic diversity was highest within Iberian wild populations. Only
      two new amino acid polymorphisms were found, both in O. c. algirus. 

PMID- 26219230
TI  - Mapping and recombination analysis of two moth colour mutations, Black moth and
      Wild wing spot, in the silkworm Bombyx mori.
AB  - Many lepidopteran insects exhibit body colour variations, where the high
      phenotypic diversity observed in the wings and bodies of adults provides
      opportunities for studying adaptive morphological evolution. In the silkworm
      Bombyx mori, two genes responsible for moth colour mutation, Bm and Ws, have been
      mapped to 0.0 and 14.7 cM of the B. mori genetic linkage group 17; however, these
      genes have not been identified at the molecular level. We performed positional
      cloning of both genes to elucidate the molecular mechanisms that underlie the
      moth wing- and body-colour patterns in B. mori. We successfully narrowed down Bm
      and Ws to ~2-Mb-long and 100-kb-long regions on the same scaffold Bm_scaf33. Gene
      prediction analysis of this region identified 77 candidate genes in the Bm
      region, whereas there were no candidate genes in the Ws region. Fluorescence in
      situ hybridisation analysis in Bm mutant detected chromosome inversion, which
      explains why there are no recombination in the corresponding region. The
      comparative genomic analysis demonstrated that the candidate regions of both
      genes shared synteny with a region associated with wing- and body-colour
      variations in other lepidopteran species including Biston betularia and
      Heliconius butterflies. These results suggest that the genes responsible for wing
      and body colour in B. mori may be associated with similar genes in other
      Lepidoptera. 

PMID- 26219231
TI  - What can aquatic gastropods tell us about phenotypic plasticity? A review and
      meta-analysis.
AB  - There have been few attempts to synthesise the growing body of literature on
      phenotypic plasticity to reveal patterns and generalities about the extent and
      magnitude of plastic responses. Here, we conduct a review and meta-analysis of
      published literature on phenotypic plasticity in aquatic (marine and freshwater)
      gastropods, a common system for studying plasticity. We identified 96 studies,
      using pre-determined search terms, published between 1985 and November 2013. The
      literature was dominated by studies of predator-induced shell form, snail growth
      rates and life history parameters of a few model taxa, accounting for 67% of all
      studies reviewed. Meta-analyses indicated average plastic responses in shell
      thickness, shell shape, and growth and fecundity of freshwater species was at
      least three times larger than in marine species. Within marine gastropods,
      species with planktonic development had similar average plastic responses to
      species with benthic development. We discuss these findings in the context of the
      role of costs and limits of phenotypic plasticity and environmental heterogeneity
      as important constraints on the evolution of plasticity. We also consider
      potential publication biases and discuss areas for future research, indicating
      well-studied areas and important knowledge gaps. 

PMID- 26219232
TI  - FACTORS ASSOCIATED WITH POSTTRAUMATIC STRESS DISORDER FOLLOWING MODERATE TO
      SEVERE TRAUMATIC BRAIN INJURY: A PROSPECTIVE STUDY.
AB  - BACKGROUND: This study prospectively examined the relationship between preinjury,
      injury-related, and postinjury factors and posttraumatic stress disorder (PTSD)
      following moderate to severe traumatic brain injury (TBI). METHOD: Two hundred
      and three participants were recruited during inpatient admission following
      moderate to severe TBI. Participants completed an initial assessment soon after
      injury and were reassessed at 3, 6, and 12 months, 2, 3, 4, and 5 years
      postinjury. The Structured Clinical Interview for the Diagnostic and Statistical
      Manual of Mental Disorders-fourth edition was used to diagnose pre- and
      postinjury PTSD and other psychiatric disorders. The Glasgow Outcome Scale
      Extended (GOSE) and the Quality of Life Inventory (QOLI) were used to evaluate
      functional and psychosocial outcome from 6 months postinjury. RESULTS: The
      frequency of PTSD ranged between 0.5 and 9.4% during the 5-year period,
      increasing throughout the first 12 months and declining thereafter. After
      controlling for other predictors, shorter posttraumatic amnesia duration (odds
      ratio = 0.96, 95% CI = 0.92-1.00), other concurrent psychiatric disorder (odds
      ratio = 14.22, 95% CI = 2.68-75.38), and lower GOSE (odds ratio = 0.38, 95% CI =
      0.20-0.72) and QOLI scores (odds ratio = 0.97, 95% CI = 0.95-0.97) were
      associated with greater odds of having injury-related PTSD. DISCUSSION: The
      results of this study indicate that while shorter posttraumatic amnesia duration
      is associated with PTSD, greater TBI severity does not prevent PTSD from
      evolving. Patients with PTSD experienced high rates of psychiatric comorbidity
      and poorer functional and quality of life outcomes after TBI. CONCLUSION: There
      is a need to direct clinical attention to early identification and treatment of
      PTSD following TBI to improve outcomes.

PMID- 26219233
TI  - Bacterial membranes enhance the immunogenicity and protective capacity of the
      surface exposed tick Subolesin-Anaplasma marginale MSP1a chimeric antigen.
AB  - Ticks are vectors of diseases that affect humans and animals worldwide. Tick
      vaccines have been proposed as a cost-effective and environmentally sound
      alternative for tick control. Recently, the Rhipicephalus microplus Subolesin
      (SUB)-Anaplasma marginale MSP1a chimeric antigen was produced in Escherichia coli
      as membrane-bound and exposed protein and used to protect vaccinated cattle
      against tick infestations. In this research, lipidomics and proteomics
      characterization of the E. coli membrane-bound SUB-MSP1a antigen showed the
      presence of components with potential adjuvant effect. Furthermore, vaccination
      with membrane-free SUB-MSP1a and bacterial membranes containing SUB-MSP1a showed
      that bacterial membranes enhance the immunogenicity of the SUB-MSP1a antigen in
      animal models. R. microplus female ticks were capillary-fed with sera from pigs
      orally immunized with membrane-free SUB, membrane bound SUB-MSP1a and saline
      control. Ticks ingested antibodies added to the blood meal and the effect of
      these antibodies on reduction of tick weight was shown for membrane bound SUB
      MSP1a but not SUB when compared to control. Using the simple and cost-effective
      process developed for the purification of membrane-bound SUB-MSP1a, endotoxin
      levels were within limits accepted for recombinant vaccines. These results
      provide further support for the development of tick vaccines using E. coli
      membranes exposing chimeric antigens such as SUB-MSP1a. 

PMID- 26219235
TI  - Plasmodium vivax: a roadblock on the quest to eliminate malaria.

PMID- 26219236
TI  - Probing the mechanism of CO2 capture in diamine-appended metal-organic frameworks
      using measured and simulated X-ray spectroscopy.
AB  - Diamine-appended metal-organic frameworks display great promise for carbon
      capture applications, due to unusual step-shaped adsorption behavior that was
      recently attributed to a cooperative mechanism in which the adsorbed CO2
      molecules insert into the metal-nitrogen bonds to form ordered ammonium carbamate
      chains [McDonald et al., Nature, 2015, 519, 303]. We present a detailed study of
      this mechanism by in situ X-ray absorption spectroscopy and density functional
      theory calculations. Distinct spectral changes at the N and O K-edges are
      apparent upon CO2 adsorption in both mmen-Mg2(dobpdc) and mmen-Mn2(dobpdc), and
      these are evaluated based upon computed spectra from three potential adsorption
      structures. The computations reveal that the observed spectral changes arise from
      specific electronic states that are signatures of a quasi-trigonal planar
      carbamate species that is hydrogen bonded to an ammonium cation. This eliminates
      two of the three structures studied, and confirms the insertion mechanism. We
      note the particular sensitivity of X-ray absorption spectra to the insertion step
      of this mechanism, underpinning the strength of the technique for examining
      subtle chemical changes upon gas adsorption. 

PMID- 26219234
TI  - Rice consumption and cancer incidence in US men and women.
AB  - While both the 2012 and 2014 Consumer Reports concerned arsenic levels in US
      rice, no previous study has evaluated long-term consumption of total rice, white
      rice and brown rice in relation to risk of developing cancers. We investigated
      this in the female Nurses' Health Study (1984-2010), and Nurses' Health Study II
      (1989-2009), and the male Health Professionals Follow-up Study (1986-2008), which
      included a total of 45,231 men and 160,408 women, free of cancer at baseline.
      Validated food frequency questionnaires were used to measure rice consumption at
      baseline and repeated almost every 4 years thereafter. We employed Cox
      proportional hazards regression model to estimate multivariable relative risks
      (RRs) and 95% confidence intervals (95% CIs). During up to 26 years of follow-up,
      we documented 31,655 incident cancer cases (10,833 in men and 20,822 in women).
      Age-adjusted results were similar to multivariable-adjusted results. Compared to
      participants with less than one serving per week, the multivariable RRs of
      overall cancer for individuals who ate at least five servings per week were 0.97
      for total rice (95% CI: 0.85-1.07), 0.87 for white rice (95% CI: 0.75-1.01), and
      1.17 for brown rice (95% CI: 0.90-1.26). Similar non-significant associations
      were observed for specific sites of cancers including prostate, breast, colon and
      rectum, melanoma, bladder, kidney, and lung. Additionally, the null associations
      were observed among European Americans and non-smokers, and were not modified by
      BMI. Long-term consumption of total rice, white rice or brown rice was not
      associated with risk of developing cancer in US men and women. 

PMID- 26219237
TI  - Generation of Evc2/Limbin global and conditional KO mice and its roles during
      mineralized tissue formation.
AB  - Ellis-van Creveld (EvC) syndrome (OMIM 225500) is an autosomal recessive disease
      characterized with chondrodysplastic dwarfism in association with abnormalities
      in oral cavity. Ciliary proteins EVC and EVC2 have been identified as causative
      genes and they play an important role on Hedgehog signal transduction. We have
      also identified a causative gene LIMBIN for bovine chondrodysplastic dwarfism
      (bcd) that is later identified as the bovine ortholog of EVC2. Here, we report
      generation of conventional and conditional mutant Evc2/Limbin alleles that mimics
      mutations found in EvC patients and bcd cattle. Resulted homozygous mice showed
      no ciliary localization of EVC2 and EVC and displayed reduced Hedgehog signaling
      activity in association with skeletal and oral defects similar to the EvC
      patients. Cartilage-specific disruption of Evc2/Limbin resulted in similar but
      milder skeletal defects, whereas osteoblast-specific disruption did not cause
      overt changes in skeletal system. Neural crest-specific disruption of Evc2/Limbin
      resulted in defective incisor growth similar to that seen in conventional
      knockouts; however, differentiation of amelobolasts was relatively normal in the
      conditional knockouts. These results showcased functions of EVC2/LIMBIN during
      formation of mineralized tissues. Availability of the conditional allele for this
      gene should facilitate further detailed analyses of the role of EVC2/LIMBIN in
      pathogenesis of EvC syndrome. genesis 53:612-626, 2015. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26219238
TI  - Anaplastic Thyroid Cancer: Large Database, Cautious Interpretations.

PMID- 26219239
TI  - Utilization of Multiple I-125 Radioactive Seeds in the Same Breast is Safe and
      Feasible: A Multi-institutional Experience.
AB  - OBJECTIVE: Radioactive seed localization has been shown to be a reliable and safe
      alternative to wire localization in breast surgery, but little is known about the
      use of multiple localization seeds. This study evaluated the utilization of
      multiple seeds in the same breast. METHODS: All patients who underwent
      localization of breast lesions using multiple I-125 seeds at three Mayo Clinic
      sites between January 2003 and June 2014 were included. RESULTS: A total of 461
      operations were performed during an 11.5-year study period. The indications for
      multiple seed placement in the same breast included multiple lesions (n = 258),
      bracketing (n = 110), multiple lesions and bracketing (n = 67), and a second
      inserted for more precise localization (n = 26). Among patients with bracketing
      seeds, the mean distance between seeds was 45 (range 8-110) mm. Removal of the
      targeted lesion was successful in all cases; 96% of bracketed lesions were
      removed as a single specimen, and a 98% retrieval rate within the first specimen
      was obtained. In total 108 of 382 (28%) patients had close or positive margin
      resulting in a second procedure and 60 of 177 (34%) patients with bracketing
      procedures underwent reexcision of positive margins or culminated in a
      mastectomy. Routine intraoperative frozen section analysis was associated with a
      lower reoperation rate compared with a selective approach to intraoperative
      margin assessment. CONCLUSIONS: The use of multiple radioactive seeds for
      localizing multiple lesions in the same breast or bracketing lesions is feasible
      and safe. Because of the extent of disease, a substantial percentage of these
      patients require margin reexcision or conversion to mastectomy.

PMID- 26219240
TI  - The Ethics of Breast Surgery.
AB  - Breast surgery has evolved as a subspecialty of general surgery and requires a
      working knowledge of benign and malignant diseases, surgical techniques, shared
      decision-making with patients, collaboration with a multi-disciplinary team, and
      a basic foundation in surgical ethics. Ethics is defined as the practice of
      analyzing, evaluating, and promoting best conduct based upon available standards.
      As new information is obtained or as cultural values change, best conduct may be
      re-defined. In 2014, the Ethics Committee of the ASBrS acknowledged numerous
      ethical issues, specific to the practice of breast surgery. This independent
      review of ethical concerns was created by the Ethics Committee to provide a
      resource for ASBrS members as well as other surgeons who perform breast surgery.
      In this review, the professional, clinical, research and technology
      considerations that breast surgeons face are reviewed with guidelines for ethical
      physician behavior. 

PMID- 26219241
TI  - Multigene Panel Testing Detects Equal Rates of Pathogenic BRCA1/2 Mutations and
      has a Higher Diagnostic Yield Compared to Limited BRCA1/2 Analysis Alone in
      Patients at Risk for Hereditary Breast Cancer.
AB  - BACKGROUND: Recently introduced multigene panel testing including BRCA1 and BRCA2
      genes for hereditary cancer risk has raised concerns with the ability to detect
      all deleterious BRCA1/2 mutations compared to older methods of sequentially
      testing BRCA1/2 separately. The purpose of this study was to evaluate rates of
      pathogenic BRCA1/2 mutations and variants of uncertain significance (VUS) between
      previous restricted algorithms of genetic testing and newer approaches of
      multigene testing. METHODS: Data was collected retrospectively from 966 patients
      who underwent genetic testing at one of three sites from a single institution.
      Test results were compared between patients who underwent BRCA1/2 testing only
      (limited group, n = 629) to those who underwent multigene testing with 5-43
      cancer-related genes (panel group, n = 337). RESULTS: Deleterious BRCA1/2
      mutations were identified in 37 patients, with equivalent rates between limited
      and panel groups (4.0 vs. 3.6%, respectively, p = 0.86). Thirty-nine patients had
      a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5 vs. 3.3%,
      respectively, p = 0.49). On multivariate analysis, there was no difference in
      detection of either BRCA1/2 mutations or VUS between both groups. Of patients
      undergoing panel testing, an additional 3.9 % (n = 13) had non-BRCA pathogenic
      mutations and 13.4% (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and
      ATM were the most common non-BRCA mutations identified. CONCLUSIONS: Multigene
      panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited
      testing and increases the diagnostic yield. Panel testing increases the VUS rate,
      mainly as a result of non-BRCA genes. Patients at risk for hereditary breast
      cancer can safely benefit from up-front, more efficient, multigene panel testing.

PMID- 26219242
TI  - A Prospective Randomized Trial of Enteral Nutrition After Thoracoscopic
      Esophagectomy for Esophageal Cancer.
AB  - BACKGROUND: Several studies have reported that postoperative enteral nutrition
      (EN) reduced complications and decreased weight loss and hospital stay periods;
      however, the majority of patients analyzed in these studies underwent open
      thoracic surgery. No studies have been conducted regarding EN in patients after
      thoracoscopic esophagectomy as a less invasive surgery. The aim of this study was
      to investigate the efficacy of EN after thoracoscopic esophagectomy. METHODS:
      Fifty patients who underwent thoracoscopic esophagectomy for esophageal cancer
      were divided into two groups: parenteral nutrition (PN; n = 25) and EN (n = 25).
      The rate of weight loss at postoperative day (POD) 14, levels of prealbumin at
      POD 10, postoperative complications until POD 14, and other perioperative data
      were collected for each group. RESULTS: This study analyzed data for 47 patients.
      The rate of weight loss at POD 14 was significantly lower in the EN group (3.0 +/
      3.2 %) than in the PN group (5.1 +/- 3.7 %; p = 0.020). Prealbumin levels were
      21.0 +/- 7.5 mg/dL in the PN group and 18.4 +/- 5.8 mg/dL in the EN group at POD
      10, with no significant differences between the groups. However, the incidence of
      postoperative pneumonia was higher in the PN group (30.4 %) than in the EN group
      (12.5 %). CONCLUSIONS: EN could suppress weight loss and reduce the incidence of
      pneumonia after thoracoscopic esophagectomy.

PMID- 26219243
TI  - Early Postoperative Outcomes in Breast Conservation Surgery Versus Simple
      Mastectomy with Implant Reconstruction: A NSQIP Analysis of 11,645 Patients.
AB  - BACKGROUND: Little has been studied that compares early postoperative outcomes
      between breast conservation surgery (BCS) and simple mastectomy with implant
      reconstruction (SM). Our goal was to utilize a large-volume database to compare
      such outcomes in women with early stage breast cancer. METHODS: The National
      Surgery Quality Improvement Program (NSQIP) database was searched for patients
      who underwent partial or complete mastectomy between 2009 and 2012. Exclusion
      criteria eliminated potential confounding factors. We compared preoperative
      comorbidities and postoperative complication rates between each treatment group
      by Chi square and two-sample t tests; we also determined the odds ratios for the
      likelihood of adverse events in a number of categories. RESULTS: A total of
      11,645 patients met the study criteria: 9571 underwent BCS and 2074 underwent SM
      with implant reconstruction. The baseline characteristics of the two groups
      showed significant differences for age (61.7 years in BCS, 53.5 years in SM),
      body mass index (29.6 kg/m(2) in BCS, 27.0 kg/m(2) in SM), and rates of
      hypertension (47.0 % in BCS, 25.6 % in SM), coronary artery disease (1.3 % in
      BCS, 0.6 % in SM), chronic obstructive pulmonary disease (2.4 % in BCS, 1.0 % in
      SM), and diabetes (11.7 % in BCS, 5.9 % in SM). Statistical analysis between each
      treatment modality revealed that the SM with implant group had significantly
      higher total complication (5.5 vs. 2.1 % in BCS), wound (2.8 vs. 1.4 % in BCS),
      infection (1.9 vs. 0.4 % in BCS), and bleeding (0.2 vs. 0.05 % in BCS) rates than
      the BCS group. CONCLUSIONS: BCS has fewer overall early postoperative wound,
      infectious, and bleeding complications despite a significantly higher rate of
      preexisting risk factors.

PMID- 26219244
TI  - Understanding the conformational behaviour of Ac-Ala-NHMe in different media. A
      joint NMR and DFT study.
AB  - The conformational behaviour of Ac-Ala-NHMe was studied in the gas-phase and in
      solution by theoretical calculations (B3LYP-D3/aug-cc-pVDZ level) and
      experimental (1)H NMR. The conformational preferences of this compound were shown
      to result from a complex interplay between the strengths of possible
      intramolecular hydrogen bonds, steric interactions, hyperconjugation, entropy
      effects and the overall dipole moments. The Ac-Ala-N(Me)2 derivative was studied
      in addition, to design a system akin to Ac-Ala-NHMe, but with disrupted
      intramolecular hydrogen bonds involving the -NHMe group, mimicking the effect of
      polar protic solvents. 

PMID- 26219245
TI  - Configuration of watermelon fruit quality in response to rootstock-mediated
      harvest maturity and postharvest storage.
AB  - BACKGROUND: The configuration of watermelon fruit quality was analysed in a multi
      factorial approach accounting for the effects of grafting, harvest maturity and
      postharvest storage. Diploid, seeded, hybrid cv. Pegasus, cultivated as scion on
      interspecific hybrid squash rootstock TZ148 and as non-grafted control, was
      stored at 25  degrees C following sequential harvests from the onset of ripening
      to over-maturity. RESULTS: Delayed rootstock-mediated climax in pulp lycopene and
      chroma was observed, while both were heightened by postharvest storage when
      harvest preceded full maturity. Pulp firmness was increased by 46.5% on TZ148,
      while postharvest decrease in firmness was non-significant. Non-grafted fruits
      attained their peak in pulp carbohydrate content earlier during ripening.
      Monosaccharide content declined and sucrose content increased both preharvest and
      postharvest; overall sugar content declined by 4.3% during storage. Pulp acidity
      decreased steadily with ripening but was moderately increased by grafting.
      Citrulline content increased by 12.5% on TZ148; moreover, it climaxed with
      ripening and declined with storage only in grafted fruit. CONCLUSION: Grafting
      enhances pulp texture and bioactive composition. Potential suppression of sugar
      content as a result of grafting is minimized at full commercial maturity. Brief
      postharvest ambient storage enhances pulp lycopene and chroma, especially in
      early-picked fruit, notwithstanding the depletion of monosaccharides and
      citrulline and a limited deterioration of texture. (c) 2015 Society of Chemical
      Industry.

PMID- 26219247
TI  - Embryo Form Project: An original technique for the three-dimensional
      reconstruction of human embryo morphology.
AB  - Our current knowledge on the developmental stages of human embryogenesis has
      derived from limited numbers of classical studies. Computer technology now
      permits accurate 3D reconstruction of embryo morphology from serial histological
      sections. We present a successful technique that uses either fresh or preserved
      serial histological sections to generate highly detailed 3D image reconstructions
      of very small human embryos. We present the data we obtained from the
      reconstruction in virtual space of previously sectioned 15 and 22.5mm embryos.
      Their morphologies were studied using a DICOM viewer which permitted the analysis
      of any specific structure in any required orientation. To our knowledge, this is
      the first time human embryos have been reconstructed in this way. We believe that
      this reconstruction technique could improve our knowledge on embryo
      morphogenesis, especially if coupled to the study of genes involved in embryonic
      development. It may also prove to be a useful pedagogical tool. 

PMID- 26219248
TI  - The Importance of Peripheral and Local Blood Analysis for Evaluation of Nitric
      Oxide and Asymmetric Dimethylarginine Before and After Varicocelectomy.

PMID- 26219246
TI  - The prothrombotic activity of cancer cells in the circulation.
AB  - The hemostatic system is often subverted in patients with cancer, resulting in
      life-threatening venous thrombotic events. Despite the multifactorial and complex
      etiology of cancer-associated thrombosis, changes in the expression and activity
      of cancer-derived tissue factor (TF) - the principle initiator of the coagulation
      cascade - are considered key to malignant hypercoagulopathy and to the
      pathophysiology of thrombosis. However, many of the molecular and cellular
      mechanisms coupling the hemostatic degeneration to malignancy remain largely
      uncharacterized. In this review we discuss some of the tumor-intrinsic and tumor
      extrinsic mechanisms that may contribute to the prothrombotic state of cancer,
      and we bring into focus the potential for circulating tumor cells (CTCs) in
      advancing our understanding of the field. We also summarize the current status of
      anti-coagulant therapy for the treatment of thrombosis in patients with cancer. 

PMID- 26219249
TI  - Group 14 inorganic hydrocarbon analogues.
AB  - Hydrocarbons are ubiquitous in our daily lives due to their use as commodity
      materials (e.g. polyethylene) and fuels. Heavier Group 14 element hydrides,
      termed herein as "inorganic hydrocarbon analogues", often exhibit divergent
      reactivity with respect to their organic congeners. In addition to expanding our
      general knowledge with respect to periodic trends, inorganic Group 14 hydrides
      have a prominent role in industry as gaseous, and now liquid-phase, precursors to
      semi-conducting films; furthermore, these species have been successfully used to
      prepare nanomaterials of controllable shape and function. This Review covers
      these exciting fields of study along with providing computationally-derived
      insights from the literature as they pertain to the reactivity and structural
      diversity of inorganic hydrocarbon analogues (118 references). 

PMID- 26219250
TI  - Turing pattern dynamics and adaptive discretization for a super-diffusive Lotka
      Volterra model.
AB  - In this paper we analyze the effects of introducing the fractional-in-space
      operator into a Lotka-Volterra competitive model describing population super
      diffusion. First, we study how cross super-diffusion influences the formation of
      spatial patterns: a linear stability analysis is carried out, showing that cross
      super-diffusion triggers Turing instabilities, whereas classical (self) super
      diffusion does not. In addition we perform a weakly nonlinear analysis yielding a
      system of amplitude equations, whose study shows the stability of Turing steady
      states. A second goal of this contribution is to propose a fully adaptive
      multiresolution finite volume method that employs shifted Grunwald gradient
      approximations, and which is tailored for a larger class of systems involving
      fractional diffusion operators. The scheme is aimed at efficient dynamic mesh
      adaptation and substantial savings in computational burden. A numerical
      simulation of the model was performed near the instability boundaries, confirming
      the behavior predicted by our analysis. 

PMID- 26219251
TI  - Rise of the Molecular Machines.

PMID- 26219252
TI  - Deep and high-resolution three-dimensional tracking of single particles using
      nonlinear and multiplexed illumination.
AB  - Molecular trafficking within cells, tissues and engineered three-dimensional
      multicellular models is critical to the understanding of the development and
      treatment of various diseases including cancer. However, current tracking methods
      are either confined to two dimensions or limited to an interrogation depth of ~15
      MUm. Here we present a three-dimensional tracking method capable of quantifying
      rapid molecular transport dynamics in highly scattering environments at depths up
      to 200 MUm. The system has a response time of 1 ms with a temporal resolution
      down to 50 MUs in high signal-to-noise conditions, and a spatial localization
      precision as good as 35 nm. Built on spatiotemporally multiplexed two-photon
      excitation, this approach requires only one detector for three-dimensional
      particle tracking and allows for two-photon, multicolour imaging. Here we
      demonstrate three-dimensional tracking of epidermal growth factor receptor
      complexes at a depth of ~100 MUm in tumour spheroids. 

PMID- 26219253
TI  - Medical Costs of Persons with Drug Use Disorders Among Medicaid Managed Care
      Beneficiaries in Puerto Rico : Comparison of the Direct Services Costs Incurred
      by Beneficiaries With and Without a Drug Use Disorder.
AB  - Drug use disorders (DUDs) can substantially increase the costs of health care,
      especially when left untreated. Yet, not much is known about the specific types
      of medical services that give rise to these cost differences. This study aimed to
      estimate the medical costs of beneficiaries with DUDs enrolled in the Medicaid
      Managed Care (MMC) program in Puerto Rico using claims data. These were compared
      to those of a matched group of patients without DUDs. On average, each
      beneficiary with a DUD incurred in $4539 annually on medical services compared to
      $2601 in the matched comparison group, a cost differential of $1938. Close to
      half of these additional medical costs (43.4%) were generated in the physical
      health services sector. Counts of service claims were also higher for
      beneficiaries with DUDs than for beneficiaries without DUDs in all service types,
      except in outpatient and laboratory services for physical health. A host of
      access strategies and treatment modalities should be tested to assess the extent
      to which providing adequate access and adequate treatment for a DUD can
      contribute to cost savings. 

PMID- 26219254
TI  - A Statewide Pediatric Psychiatry Consultation to Primary Care Program and the
      Care of Children with Trauma-related Concerns.

PMID- 26219255
TI  - Bi-content micro-collagen chip provides contractility-based biomechanical readout
      for phenotypic drug screening with expanded and profiled targets.
AB  - Phenotypic screening has regained momentum in the pharmaceutical industry owing
      to its success over target-based screening. Most phenotypic screening relies on
      nonspecific biochemical readouts regarding cellular viability, which hampers the
      discovery of novel drug mechanisms of action (MOAs). Here we present a
      Contractility-based bi-Content micro-Collagen Chip (3CChip), which establishes
      cellular contractility as a biomechanics-related phenotype for drug screening. Bi
      content analysis of cell contractility (imaged by iPhone) and viability suggests
      that the label-free contractility-based analysis exhibits superior sensitivity to
      compounds targeting contractile elements (e.g. focal adhesion, cytoskeleton),
      resulting in a enlarged target pool for drug assessment. Six typical readout
      patterns of drug response are summarized according to the relative positions of
      the contraction/viability curves, and drug targets are profiled into three
      categories (biomechanical, biochemical and housekeeping) by 3CChip, which will
      benefit subsequent target identification. The simple-to-use and effective 3CChip
      offers a robust platform for micro-tissue-based functional screening and may lead
      to a new era of mechanism-informed phenotypic drug discovery. 

PMID- 26219256
TI  - Protein quality and quantity control at the yeast ER.

PMID- 26219258
TI  - High-throughput simultaneous screen and counterscreen identifies
      homoharringtonine as synthetic lethal with von Hippel-Lindau loss in renal cell
      carcinoma.
AB  - Renal cell carcinoma (RCC) accounts for 85% of primary renal neoplasms, and is
      rarely curable when metastatic. Approximately 70% of RCCs are clear-cell type
      (ccRCC), and in >80% the von Hippel-Lindau (VHL) gene is mutated or silenced. We
      developed a novel, high-content, screening strategy for the identification of
      small molecules that are synthetic lethal with genes mutated in cancer. In this
      strategy, the screen and counterscreen are conducted simultaneously by
      differentially labeling mutant and reconstituted isogenic tumor cell line pairs
      with different fluorochromes and using a highly sensitive high-throughput imaging
      based platform. This approach minimizes confounding factors from sequential
      screening, and more accurately replicates the in vivo cancer setting where cancer
      cells are adjacent to normal cells. A screen of ~12,800 small molecules
      identified homoharringtonine (HHT), an FDA-approved drug for treating chronic
      myeloid leukemia, as a VHL-synthetic lethal agent in ccRCC. HHT induced apoptosis
      in VHL-mutant, but not VHL-reconstituted, ccRCC cells, and inhibited tumor growth
      in 30% of VHL-mutant patient-derived ccRCC tumorgraft lines tested. Building on a
      novel screening strategy and utilizing a validated RCC tumorgraft model
      recapitulating the genetics and drug responsiveness of human RCC, these studies
      identify HHT as a potential therapeutic agent for a subset of VHL-deficient
      ccRCCs. 

PMID- 26219257
TI  - Anti-tumoral effect of desmethylclomipramine in lung cancer stem cells.
AB  - Lung cancer is the most feared of all cancers because of its heterogeneity and
      resistance to available treatments. Cancer stem cells (CSCs) are the cell
      population responsible for lung cancer chemoresistance and are a very good model
      for testing new targeted therapies. Clomipramine is an FDA-approved
      antidepressant drug, able to inhibit in vitro the E3 ubiquitin ligase Itch and
      potentiate the pro-apoptotic effects of DNA damaging induced agents in several
      cancer cell lines. Here, we investigated the potential therapeutic effect of
      desmethylclomipramine (DCMI), the active metabolite of Clomipramine, on the CSCs
      homeostasis. We show that DCMI inhibits lung CSCs growth, decreases their
      stemness potential and increases the cytotoxic effect of conventional
      chemotherapeutic drugs. Being DCMI an inhibitor of the E3 ubiquitin ligase Itch,
      we also verified the effect of Itch deregulation on CSCs survival. We found that
      the siRNA-mediated depletion of Itch induces similar anti-proliferative effects
      on lung CSCs, suggesting that DCMI might exert its effect, at least in part, by
      inhibiting Itch. Notably, Itch expression is a negative prognostic factor in two
      primary lung tumors datasets, supporting the potential clinical relevance of Itch
      inhibition to circumvent drug resistance in the treatment of lung cancer. 

PMID- 26219259
TI  - Deletion of Smad3 improves cardiac allograft rejection in mice.
AB  - T cells play a critical role in acute allograft rejection. TGF-beta/Smad3
      signaling is a key pathway in regulating T cell development. We report here that
      Smad3 is a key transcriptional factor of TGF-beta signaling that differentially
      regulates T cell immune responses in a mouse model of cardiac allograft rejection
      in which donor hearts from BALB/c mice were transplanted into Smad3 knockout (KO)
      and wild type (WT) mice. Results showed that the cardiac allograft survival was
      prolonged in Smad3 KO recipients. This allograft protection was associated with a
      significant inhibition of proinflammatory cytokines (IL-1beta, TNF-alpha, and MCP
      1) and infiltration of neutrophils, CD3+ T cells, and F4/80+ macrophages.
      Importantly, deletion of Smad3 markedly suppressed T-bet and IFN-gamma while
      enhancing GATA3 and IL-4 expression, resulting in a shift from the Th1 to Th2
      immune responses. Furthermore, mice lacking Smad3 were also protected from the
      Th17-mediated cardiac injury, although the regulatory T cell (Treg) response was
      also suppressed. In conclusion, Smad3 is an immune regulator in T cell-mediated
      cardiac allograft rejection. Loss of Smad3 results in a shift from Th1 to Th2 but
      suppressing Th17 immune responses. Thus, modulation of TGF-beta/Smad3 signaling
      may be a novel therapy for acute allograft rejection. 

PMID- 26219261
TI  - Developmental Links Between Children's Working Memory and their Social Relations
      with Teachers and Peers in the Early School Years.
AB  - This study assessed the developmental links between children's working memory
      development and their relations with teachers and peers across 2 years of
      kindergarten and early elementary school. Kindergarten and first grade children,
      N = 1109, 50% boys, were followed across 2 school-years. Children were assessed
      across 3 waves, in the fall and spring of the first school-year (within school
      year), and finally in the spring of the second school-year. Working memory was
      assessed using a visuo-spatial working memory task. The developmental links
      between working memory and child-reported teacher-child relationship quality
      (warmth and conflict) and peer-nominated likeability and friendedness were
      assessed using autoregressive cross-lagged models. Lower working memory scores
      were related to increases in teacher-child conflict and decreases in teacher
      child warmth one school-year later, in addition to decreases in likeability by
      peers within the same school-year. Conversely, teacher-child conflict was
      negatively associated with the development of working memory across the studied
      period. Path estimates between working memory and social relational factors were
      similar for boys and girls. Findings show developmental links between working
      memory and social-relational factors and vice versa. These results suggest that
      children's working memory development can be fostered through pro-social
      relations with teachers in early elementary school children.

PMID- 26219260
TI  - Purification and identification of a polysaccharide from medicinal mushroom
      Amauroderma rude with immunomodulatory activity and inhibitory effect on tumor
      growth.
AB  - Medicinal mushrooms in recent years have been the subject of many experiments
      searching for anticancer properties. We previously screened thirteen mushrooms
      for their potential in inhibiting tumor growth, and found that the water extract
      of Amauroderma rude exerted the highest activity. Previous studies have shown
      that the polysaccharides contained in the water extract were responsible for the
      anticancer properties. This study was designed to explore the potential effects
      of the polysaccharides on immune regulation and tumor growth. Using the crude
      Amauroderma rude extract, in vitro experiments showed that the capacities of
      spleen lymphocytes, macrophages, and natural killer cells were all increased. In
      vivo experiments showed that the extract increased macrophage metabolism,
      lymphocyte proliferation, and antibody production. In addition, the partially
      purified product stimulated the secretion of cytokines in vitro, and in vivo.
      Overall, the extract decreased tumor growth rates. Lastly, the active compound
      was purified and identified as polysaccharide F212. Most importantly, the
      purified polysaccharide had the highest activity in increasing lymphocyte
      proliferation. In summary, this molecule may serve as a lead compound for drug
      development.

PMID- 26219262
TI  - Trajectories of Internalizing and Externalizing Behavior Problems in Children
      with Developmental Disabilities.
AB  - Children with disabilities tend to have higher levels of behavior problems than
      other children. Such problems have implications for psychopathology in the young
      adult years, with possible effects on life course opportunities such as
      employment and independent living. This investigation examines the developmental
      course of both internalizing and externalizing behavior problems by employing
      person-centered analyses to construct patterns of change in behavior problems in
      169 children (54 % male) with early diagnosed disabilities, from age 3 to age 18.
      Early childhood predictors of these patterns indicated that more adverse patterns
      of both types of behavior problems were predicted by higher maternal depressive
      symptoms. Greater impacts on the family of having a child with a disability
      predicted more adverse patterns of internalizing behavior problems. More adaptive
      patterns of externalizing behavior problems were predicted by positive maternal
      sensitivity to a child's distress. These findings suggest the need for early
      intervention focused on the family system. 

PMID- 26219263
TI  - Preschoolers' Psychopathology and Temperament Predict Mothers' Later Mood
      Disorders.
AB  - Considerable research exists documenting the relationship between maternal mood
      disorders, primarily major depressive disorder (MDD), and a variety of negative
      child outcomes. By contrast, research exploring the reverse pathway whereby child
      traits are associated with later maternal mood disorders is much more limited. We
      examined whether young children's temperament and psychopathology predicted
      maternal mood disorders approximately 6 years later. Child temperament and
      symptoms were assessed at age three using semi-structured diagnostic interviews
      and parent-report inventories. Maternal psychopathology was assessed with semi
      structured interviews when children were 3 and 9 years old. Mothers also reported
      on their marital satisfaction when children were 3 and 6 years old. Child
      temperamental negative affectivity (NA), depressive symptoms, and externalizing
      behavior problems significantly predicted maternal mood disorders over and above
      prior maternal mood, anxiety, and substance disorders. The link between
      children's early externalizing symptoms and maternal mood disorders 6 years later
      was mediated by maternal marital satisfaction 3 years after the initial
      assessment. These findings suggest that early child temperament and
      psychopathology contribute to risk for later maternal mood disorders both
      directly and through their impact on the marital system. Research indicates that
      effective treatment of maternal depression is associated with positive outcomes
      for children; however, this study suggests that treating early child problems may
      mitigate the risk of later maternal psychopathology.

PMID- 26219264
TI  - Clarification of equine dental nomenclature.

PMID- 26219265
TI  - Concurrent DNA Copy-Number Alterations and Mutations in Genes Related to
      Maintenance of Genome Stability in Uninvolved Mammary Glandular Tissue from
      Breast Cancer Patients.
AB  - Somatic mosaicism for DNA copy-number alterations (SMC-CNAs) is defined as gain
      or loss of chromosomal segments in somatic cells within a single organism. As
      cells harboring SMC-CNAs can undergo clonal expansion, it has been proposed that
      SMC-CNAs may contribute to the predisposition of these cells to genetic disease
      including cancer. Herein, the gross genomic alterations (>500 kbp) were
      characterized in uninvolved mammary glandular tissue from 59 breast cancer
      patients and matched samples of primary tumors and lymph node metastases. Array
      based comparative genomic hybridization showed 10% (6/59) of patients harbored
      one to 359 large SMC-CNAs (mean: 1,328 kbp; median: 961 kbp) in a substantial
      portion of glandular tissue cells, distal from the primary tumor site. SMC-CNAs
      were partially recurrent in tumors, albeit with considerable contribution of
      stochastic SMC-CNAs indicating genomic destabilization. Targeted resequencing of
      301 known predisposition and somatic driver loci revealed mutations and rare
      variants in genes related to maintenance of genomic integrity: BRCA1
      (p.Gln1756Profs*74, p.Arg504Cys), BRCA2 (p.Asn3124Ile), NCOR1
      (p.Pro1570Glnfs*45), PALB2 (p.Ser500Pro), and TP53 (p.Arg306*). Co-occurrence of
      gross SMC-CNAs along with point mutations or rare variants in genes responsible
      for safeguarding genomic integrity highlights the temporal and spatial neoplastic
      potential of uninvolved glandular tissue in breast cancer patients. 

PMID- 26219266
TI  - Seasonal Variation on Microbial Community and Methane Production during Anaerobic
      Digestion of Cattle Manure in Brazil.
AB  - Anaerobic digestion is an alternative method for the treatment of animal manure
      and wastewater. The anaerobic bioconversion of biomass requires a multi-step
      biological process, including microorganisms with distinct roles. The diversity
      and composition of microbial structure in pilot-scale anaerobic digestion
      operating at ambient temperature in Brazil were studied. Influence of the
      seasonal and temporal patterns on bacterial and archaeal communities were
      assessed by studying the variations in density, dynamic and diversity and
      structure. The average daily biogas produced in the summer and winter months was
      18.7 and 16 L day(-1), respectively, and there was no difference in the average
      methane yield. Quantitative PCR analysis revealed that no differences in
      abundances and dynamics were found for bacterial communities and the total number
      of Archaea in different seasons. Analysis of bacterial clone libraries revealed a
      predominance of Firmicutes (54.5 %/summer and 46.7 %/winter) and Bacteroidetes
      (31.4 %/summer and 44.4 %/winter). Within the Archaea, the phylum Euryarchaeota
      was predominant in both digesters. Phylogenetic distribution showed changes in
      percentage between the phyla identified, but no alterations were recorded in the
      quality and amount of produced methane or community dynamics. The results may
      suggest that redundancy of microbial groups may have occurred, pointing to a more
      complex microbial community in the ecosystem related to this ambient temperature
      system.

PMID- 26219267
TI  - Dissimilatory Arsenate Reduction and In Situ Microbial Activities and Diversity
      in Arsenic-rich Groundwater of Chianan Plain, Southwestern Taiwan.
AB  - Although dissimilatory arsenic reduction (DAsR) has been recognized as an
      important process for groundwater arsenic (As) enrichment, its characterization
      and association with in situ microbial activities and diversity in As-rich
      groundwater is barely studied. In this work, we collected As-rich groundwater at
      depths of 23, 300, and 313 m, respectively, from Yenshui-3, Budai-Shinwen, and
      Budai-4 of Chianan plain, southwestern Taiwan, and conducted incubation
      experiments using different electron donors, acceptors, and sulfate-reducing
      bacterial inhibitor (tungstate) to characterize DAsR. Moreover, bacterial
      diversity was evaluated using 454-pyrosequencing targeting bacterial 16S rRNAs.
      MPN technique was used to enumerate microorganisms with different in situ
      metabolic functions. The results revealed that DAsR in groundwater of Chianan
      plain was a biotic phenomenon (as DAsR was totally inhibited by filter
      sterilization), enhanced by the type of electron donor (in this case, lactate
      enhanced DAsR but acetate and succinate did not), and limited by the availability
      of arsenate. In addition to oxidative recycling of As(III), dissolution of As(V)
      saturated manganese and iron minerals by indigenous dissimilatory Mn(IV)- and
      Fe(III)-reducing bacteria, and abiotic oxidation of As(III) with Mn(IV)
      regenerated As(V) in the groundwater. Sulfate-respiring bacteria contributed 7.4
      and 28.2 % to the observed DAsR in groundwater of Yinshui-3 and Budai-Shinwen,
      respectively, whereas their contribution was negligible in groundwater of Budai
      4. A noticeable variation in dominant genera Acinetobacter and Bacillus was
      observed within the groundwater. Firmicutes dominated in highly As-rich
      groundwater of Yenshui-3, whereas Proteobacteria dominated in comparatively less
      As-rich groundwater of Budai-Shinwen and Budai 4.

PMID- 26219269
TI  - Stressful life events and leukocyte telomere attrition in adulthood: a
      prospective population-based cohort study.
AB  - BACKGROUND: Telomere attrition might be one of the mechanisms through which
      psychosocial stress leads to somatic disease. To date it is unknown if exposure
      to adverse life events in adulthood is associated with telomere shortening
      prospectively. In the current study we investigated whether life events are
      associated with shortening of telomere length (TL). METHOD: Participants were
      1094 adults (mean age 53.1, range 33-79 years) from the PREVEND cohort. Data were
      collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6
      years (T3). Life events were assessed with an adjusted version of the List of
      Threatening Events (LTE). TL was measured by monochrome multiplex quantitative
      PCR at T1, T2, and T3. A linear mixed model was used to assess the effect of
      recent life events on TL prospectively. Multivariable regression analyses were
      performed to assess whether the lifetime life events score or the score of life
      events experienced before the age of 12 predicted TL cross-sectionally. All final
      models were adjusted for age, sex, body mass index, presence of chronic diseases,
      frequency of sports, smoking status, and level of education. RESULTS: Recent life
      events significantly predicted telomere attrition prospectively (B = -0.031, p =
      0.007). We were not able to demonstrate a significant cross-sectional
      relationship between the lifetime LTE score and TL. Nor did we find exposure to
      adverse life events before the age of 12 to be associated with TL in adulthood.
      CONCLUSIONS: Exposure to recent adverse life events in adulthood is associated
      with telomere attrition prospectively.

PMID- 26219270
TI  - Construction of a high efficiency copper adsorption bacterial system via peptide
      display and its application on copper dye polluted wastewater.
AB  - For the construction of an efficient copper waste treatment system, a cell
      surface display strategy was employed. The copper adsorption ability of
      recombinant bacterial strains displaying three different copper binding peptides
      were evaluated in LB Luria-Bertani medium (LB), artificial wastewater, and copper
      phthalocyanine containing textile dye industry wastewater samples. Structural
      characteristics of the three peptides were also analyzed by similarity-based
      structure modeling. The best binding peptide was chosen for the construction of a
      dimeric peptide display and the adsorption ability of the monomeric and dimeric
      peptide displayed strains were compared. The dimeric peptide displayed strain
      showed superior copper adsorption in all three tested conditions (LB, artificial
      wastewater, and textile dye industry wastewater). When the strains were exposed
      to copper phthalocyanine dye polluted wastewater, the dimeric peptide display
      [543.27 umol/g DCW dry cell weight (DCW)] showed higher adsorption of copper when
      compared with the monomeric strains (243.53 umol/g DCW). 

PMID- 26219268
TI  - Perceived Barriers, Facilitators and Benefits for Regular Physical Activity and
      Exercise in Patients with Rheumatoid Arthritis: A Review of the Literature.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease, which not only affects the
      joints but can also impact on general well-being and risk for cardiovascular
      disease. Regular physical activity and exercise in patients with RA have numerous
      health benefits. Nevertheless, the majority of patients with RA are physically
      inactive. This indicates that people with RA might experience additional or more
      severe barriers to physical activity or exercise than the general population.
      This narrative review provides an overview of perceived barriers, benefits and
      facilitators of physical activity and exercise in RA. Databases were searched for
      articles published until September 2014 using the terms 'rheumatoid arthritis',
      'physical activity', 'exercise', 'barriers', 'facilitators', 'benefits',
      'motivation', 'motivators' and 'enablers'. Similarities were found between
      disease-specific barriers and benefits of physical activity and exercise, e.g.
      pain and fatigue are frequently mentioned as barriers, but reductions in pain and
      fatigue are perceived benefits of physical activity and exercise. Even though
      exercise does not influence the existence of barriers, physically active patients
      appear to be more capable of overcoming them. Therefore, exercise programmes
      should enhance self-efficacy for exercise in order to achieve long-term physical
      activity and exercise behaviour. Encouragement from health professionals and
      friends/family are facilitators for physical activity and exercise. There is a
      need for interventions that support RA patients in overcoming barriers to
      physical activity and exercise and help sustain this important health behaviour. 

PMID- 26219271
TI  - Recanalization of basilar artery occlusion.

PMID- 26219273
TI  - Increasing impact of urban fine particles (PM2.5) on areas surrounding Chinese
      cities.
AB  - The negative impacts of rapid urbanization in developing countries have led to a
      deterioration in urban air quality, which brings increasing negative impact to
      its surrounding areas (e.g. in China). However, to date there has been rare
      quantitative estimation of the urban air pollution to its surrounding areas in
      China.We thus evaluated the impact of air pollution on the surrounding
      environment under rapid urbanization in Chinese prefectures during 1999 - 2011.
      We found that: (1) the urban environment generated increasing negative impact on
      the surrounding areas, and the PM2.5 concentration difference between urban and
      rural areas was particularly high in large cities. (2) Nearly half of the Chinese
      prefectures (156 out of 350) showed increased impact of urban PM2.5 pollution on
      its surrounding areas. Those prefectures were mainly located along two belts: one
      from northeast China to Sichuan province, the other from Shanghai to Guangxi
      province. Our study demonstrates the deterioration in urban air quality and its
      potential impacts on its surrounding areas in China. We hope that the results
      presented here will encourage different approaches to urbanization to mitigate
      the negative impact caused by urban air pollution, both in China and other
      rapidly developing countries. 

PMID- 26219274
TI  - Seasonal Variation of Triterpenes and Phenolic Compounds in Australian Centella
      asiatica (L.) Urb.
AB  - INTRODUCTION: Specific triterpenes, phenolic acids and flavonoids in Centella
      asiatica have been found to be bioactive. Harvesting the plant when these
      putative bioactive compounds are at their highest concentrations would provide
      consistency in their chemical profile, thus ensuring the quality and efficacy of
      derived medicinal products. OBJECTIVE: The aim of the study was to determine the
      impact of harvesting time on the contents of major triterpenoid and phenolic
      compounds in C. asiatica. METHODOLOGY: Australian C. asiatica was collected from
      a designated area in different months. The principal triterpenes (asiaticoside,
      madecassoside, asiatic acid and madecassic acid), flavonoid compounds (rutin,
      quercetin and kaempferol) and chlorogenic acid were quantitatively determined by
      HPLC-DAD analysis. RESULTS: Triterpenoid, kaempferol and chlorogenic acid content
      showed significant variation (p < 0.05) in different collecting months. The total
      content of the four triterpenes reached its highest levels in January and
      February (83.15 +/- 0.16 mg/g and 78.41 +/- 0.16 mg/g, respectively), the summer
      season of the southern hemisphere, and their lowest values in winter (June) and
      spring (October) seasons (35.65 +/- 0.20 and 35.50 +/- 0.55 mg/g, respectively).
      Similarly, the contents of chlorogenic acid and kaempferol were the highest in
      December and January (1.62 +/- 0.01 and 0.33 +/- 0.01 mg/g, respectively), and
      the lowest in June (0.06 +/- 0.01 and 0.09 +/- 0.01 mg/g, respectively).
      CONCLUSION: The results indicate that harvesting C. asiatica in summer returns
      the highest yield of the target triterpenoids, kaempferol and chlorogenic acid.

PMID- 26219275
TI  - Crystal structure of the PepSY-containing domain of the YpeB protein involved in
      germination of bacillus spores.
AB  - The crystal structure of the C-terminal domain of the Bacillus megaterium YpeB
      protein has been solved by X-ray crystallography to 1.80-A resolution. The full
      length protein is essential in stabilising the SleB cortex lytic enzyme in
      Bacillus spores, and may have a role in regulating SleB activity during spore
      germination. The YpeB-C crystal structure comprises three tandemly repeated PepSY
      domains, which are aligned to form an extended laterally compressed molecule. A
      predominantly positively charged region located in the second PepSY domain may
      provide a site for protein interactions that are important in stabilising SleB
      and YpeB within the spore.

PMID- 26219276
TI  - Label-free molecular beacon-based quadratic isothermal exponential amplification:
      a simple and sensitive one-pot method to detect DNA methyltransferase activity.
AB  - We developed a one-pot label-free molecular beacon-mediated quadratic isothermal
      exponential amplification strategy (LFMB-QIEA) for simple, rapid and sensitive
      DNA methyltransferase (MTase) activity detection. 

PMID- 26219277
TI  - Correction to MALDI-TOF-MS Platform for Integrated Proteomic and Peptidomic
      Profiling of Milk Samples Allows Rapid Detection of Food Adulterations.

PMID- 26219278
TI  - Prevalence and pattern of alcohol consumption during pregnancy in the
      Netherlands.
AB  - OBJECTIVE: To estimate the prevalence of alcohol consumption during pregnancy in
      the Netherlands in 2007 and 2010. METHOD: During two identical, nation-wide
      surveys in 2007 and 2010, questionnaires were handed out to mothers of infants
      aged <=6 months who visited a Well-Baby Clinic. By means of the questionnaire
      mothers were, in addition to questions on infant feeding practices and background
      variables, asked about their alcohol consumption before, during and after
      pregnancy. Logistic regression analyses were used to look into relationships of
      alcohol consumption with maternal and infant characteristics. RESULTS: We
      obtained 2,715 questionnaires in 2007, and 1,410 in 2010. Within 6 months before
      pregnancy, 69 % of women consumed alcohol (data from 2010). During pregnancy 22 %
      consumed alcohol in 2007, 19 % in 2010. During the first three months of
      pregnancy, 17 % (2007) and 14 % (2010) of mothers consumed alcohol. Alcohol
      consumption was mainly one glass (~10 g alcohol) on less than one occasion per
      month. Compared to 2007, in 2010 more women consumed 1-3 or >3 glasses alcohol
      per occasion (resp. 11 % to 7 % and 1.4 to 0.7 %). Older women and those with a
      higher education consumed more alcohol, as did smokers. Birth weight, gestational
      age and weight for gestational age were not associated with alcohol consumption.
      In 2007 and 2010, 2.5 % resp. 2.4 % of pregnant women both smoked and consumed
      alcohol; resp. 70 % and 75 % did neither. CONCLUSION: In contrast to Dutch
      guidelines which advice to completely abstain from alcohol, one in five women in
      the Netherlands consume alcohol during pregnancy.

PMID- 26219280
TI  - INA-RESPOND: a multi-centre clinical research network in Indonesia.
AB  - Nationally representative observational and translational research is needed to
      address the public health challenges in Indonesia due to the geographic
      disparity, recently decentralized health system, and diverse infectious disease
      priorities. To accomplish this, the Indonesian Ministry of Health in
      collaboration with the US National Institute of Health has established INA
      RESPOND (Indonesia Research Partnership on Infectious Disease) - a clinical
      research network comprising 9 referral hospitals, 7 medical faculties, and 2
      research centres across Indonesia. The network provides a forum to conduct
      research at a national scale and to address scientific questions that would be
      difficult to address in smaller research settings. Further, it is currently
      conducting multi-centre research on the etiologies of fever, sepsis, and
      tuberculosis. There are opportunities to leverage existing network resources for
      other public health research needs. INA-RESPOND is an Indonesian-led network in a
      country with diverse population groups and public health needs which is poised to
      collaborate with researchers, universities, donors, and industry worldwide. This
      paper describes the network and its goals and values, as well as the management
      structure, process for collaboration, and future vision. 

PMID- 26219279
TI  - Sphingopyxis flava sp. nov., isolated from a hexachlorocyclohexane (HCH)
      contaminated soil.
AB  - A Gram-negative-staining, aerobic, non-motile, non-spore-forming, rod-shaped and
      yellow-pigmented bacterium, designated R11HT, was isolated from a soil sample
      collected from a hexachlorocyclohexane dumpsite located at Ummari village,
      Lucknow, Uttar Pradesh, India. The 16S rRNA gene sequence similarity between
      strain R11HT and the type strains of species of genus Sphingopyxis with validly
      published names ranged from 93.75 to 97.85 %. Strain R11HT showed the highest 16S
      rRNA gene sequence similarity to Sphingopyxis indica DS15T (97.85 %), followed by
      Sphingopyxis soli JCM15910T (97.79 %), Sphingopyxis ginsengisoli KCTC 12582T
      (97.77 %) and Sphingopyxis panaciterrulae KCTC 22112T (97.34 %). The DNA G+C
      content of strain R11HT was 63.5 mol%. DNA-DNA relatedness between strain R11HT
      and its closest phylogenetic neighbours was well below the threshold value of 70
      %, which suggested that strain R11HT represents a novel species of the genus
      Sphingopyxis. The major polar lipids of strain R11HT were sphingoglycolipid and
      other lipids commonly reported in this genus, phosphatidylethanolamine,
      diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol and
      phosphatidylmonomethylethanolamine. Spermidine was detected as the major
      polyamine. The chemotaxonomic markers in strain R11HT confirmed its
      classification in the genus Sphingopyxis, i.e. Q-10 as the major ubiquinone and
      summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c), summed feature 3 (C16 :
      1omega7c and/or C16 : 1omega6c), C16 : 0 and C14 : 0 2-OH as the predominant
      fatty acids. Results obtained from DNA-DNA hybridization and chemotaxonomic and
      phenotypic analyses clearly distinguished strain R11HT from its closest
      phylogenetic neighbours. Thus, strain R11HT represents a novel species of the
      genus Sphingopyxis, for which the name Sphingopyxis flava sp. nov. is proposed.
      The type strain is R11HT ( = DSM 28472T = MCC 2778T). 

PMID- 26219281
TI  - An economic evaluation alongside a randomized controlled trial evaluating an
      individually tailored lifestyle intervention compared with usual care in people
      with familial hypercholesterolemia.
AB  - BACKGROUND: Cost-effectiveness analyses provide insight in the use of lifestyle
      interventions. To evaluate the cost-effectiveness of a lifestyle intervention
      compared to usual care in people with Familial Hypercholesterolemia, 340 people
      with FH were randomized to the intervention or control group. LDL cholesterol,
      quality of life and costs were measured at 0 and 12 months. Cost-effectiveness
      analyses were performed from a healthcare perspective using bootstrapping
      techniques. RESULTS: Non-significant decreases in LDL cholesterol and quality of
      life were found. The mean between-group difference in costs was ?-237 (95% CI 
      1,386 to 130). The incremental cost-effectiveness ratios were 1,729 per 1 mmol/l
      LDL cholesterol and 145,899 per QALY gained. Assumed that the small non
      significant decrease in LDL cholesterol is attributed to the intervention, the
      probability of cost-effectiveness of the intervention compared to usual care was
      91% per 1 mmol/l LDL cholesterol reduction and 75% per QALY gained at a ceiling
      ratio of ?20,000. CONCLUSIONS: The intervention is not cost-effective. TRIAL
      REGISTRATION: NTR1899, date 07-07-2009.

PMID- 26219285
TI  - A new protocol for concomitant needle aspiration biopsy and localization of
      solitary pulmonary nodules.
AB  - BACKGROUND: Pulmonary nodules may require thoracoscopic resection in cases where
      percutaneous needle aspiration (PCNA) is non-diagnostic or not technically
      feasible. We developed a new protocol to localize pulmonary nodules concomitantly
      with PCNA. We retrospectively reviewed the use of concomitant PCNA and
      preoperative localization under computed tomography (CT) guidance. METHODS: From
      Jan 2006 to Dec 2013, we performed PCNA and localization concomitantly on 34
      pulmonary nodules (in 33 patients) using self-made, platinum microcoils. Patients
      in which PCNA results were less likely to be non-diagnostic and who were
      anticipating thoracoscopy were eligible to participate in this study. The CT
      guided PCNA biopsy and microcoil localization was performed on the day of the
      VATS in the CT suite. The PCNA specimen was sent to the pathologist for frozen
      section pathology. If diagnosis of the lesion was not confirmed by PCNA or was
      primary lung cancer, the patient was moved to the operating room for VATS
      surgery. RESULTS: Between Jan 2006 and Dec 2013, concomitant PCNA and
      localization were successfully performed on 34 pulmonary nodules from 33 patients
      (one patient had two nodules). Of the 34 nodules, seven were diagnosed
      pathologically using PCNA, and 27 nodules that could not be diagnosed by PCNA
      were excised by thoracoscopic resection without additional procedures or time
      because of concomitant localization. There were no deaths or significant
      morbidities. Minor complications included three incidents of lung hemorrhage and
      five of pneumothorax (two required closed thoracostomy drainage). Of 34 nodules
      in which both PCNA and localization were used, thoracoscopic resections were
      performed on 33, lobectomies were performed concomitantly with thoracoscopic
      resection on 11. Intraoperative fluoroscopy was used to detect 33 of 34 nodules
      localized using the platinum microcoil (97.06 %) or to guide stapling during
      thoracoscopic resection. CONCLUSIONS: The advantages of this technique are 1)
      there is no need for further localization during thoracoscopy even in cases of
      unsuccessful PCNA, 2) it is more effective with respect to both cost and time,
      and 3) it provides greater patient comfort.

PMID- 26219286
TI  - Effects of ketamine, s-ketamine, and MK 801 on proliferation, apoptosis, and
      necrosis in pancreatic cancer cells.
AB  - BACKGROUND: Adenocarcinoma of the pancreas is one of the most aggressive cancer
      diseases affecting the human body. The oncogenic potential of this type of cancer
      is mainly characterized by its extreme growth rate triggered by the activation of
      signaling cascades. Modern oncological treatment strategies aim at efficiently
      modulating specific signaling and transcriptional pathways. Recently, anti
      tumoral potential has been proven for several substances that are not primarily
      used in cancer treatment. In some tumor entities, for example, administration of
      glutamate antagonists inhibits cell proliferation, cell cycle arrest, and finally
      cell death. To attain endogenic proof of NMDA receptor type expression in the
      pancreatic cancer cell lines PaTu8988t and Panc-1 and to investigate the impact
      of ketamine, s-ketamine, and the NMDA receptor antagonist MK 801 on
      proliferation, apoptosis, and necrosis in pancreatic carcinoma. METHODS: Cell
      proliferation was measured by means of the ELISA BrdU assay, and the apoptosis
      rate was analyzed by annexin V staining. Immunoblotting were also used. RESULTS:
      The NMDA receptor type R2a was expressed in both pancreatic carcinoma cell lines.
      Furthermore, ketamine, s-ketamine, and MK 801 significantly inhibited
      proliferation and apoptosis. CONCLUSIONS: In this study, we showed the expression
      of the NMDA receptor type R2a in pancreatic cancer cells. The NMDA antagonists
      ketamine, s-ketamine, and MK 801 inhibited cell proliferation and cell death.
      Further clinical studies are warranted to identify the impact of these agents on
      the treatment of cancer patients.

PMID- 26219287
TI  - Morphological and ecological divergence of Lilium and Nomocharis within the
      Hengduan Mountains and Qinghai-Tibetan Plateau may result from habitat
      specialization and hybridization.
AB  - BACKGROUND: Several previous studies have shown that some morphologically
      distinctive, small genera of vascular plants that are endemic to the Qinghai
      Tibetan Plateau and adjacent Hengduan Mountains appear to have unexpected and
      complex phylogenetic relationships with their putative sisters, which are
      typically more widespread and more species rich. In particular, the endemic
      genera may form one or more poorly resolved paraphyletic clades within the sister
      group despite distinctive morphology. Plausible explanations for this
      evolutionary and biogeographic pattern include extreme habitat specialization and
      hybridization. One genus consistent with this pattern is Nomocharis Franchet.
      Nomocharis comprises 7-15 species bearing showy-flowers that are endemic to the H
      D Mountains. Nomocharis has long been treated as sister to Lilium L., which is
      comprised of more than 120 species distributed throughout the temperate Northern
      Hemisphere. Although Nomocharis appears morphologically distinctive, recent
      molecular studies have shown that it is nested within Lilium, from which is
      exhibits very little sequence divergence. In this study, we have used a dated
      molecular phylogenetic framework to gain insight into the timing of morphological
      and ecological divergence in Lilium-Nomocharis and to preliminarily explore
      possible hybridization events. We accomplished our objectives using dated
      phylogenies reconstructed from nuclear internal transcribed spacers (ITS) and six
      chloroplast markers. RESULTS: Our phylogenetic reconstruction revealed several
      Lilium species nested within a clade of Nomocharis, which evolved ca. 12 million
      years ago and is itself nested within the rest of Lilium. Flat/open and horizon
      oriented flowers are ancestral in Nomocharis. Species of Lilium nested within
      Nomocharis diverged from Nomocharis ca. 6.5 million years ago. These Lilium
      evolved recurved and campanifolium flowers as well as the nodding habit by at
      least 3.5 million years ago. Nomocharis and the nested Lilium species had
      relatively low elevation ancestors (<1000 m) and underwent diversification into
      new, higher elevational habitats 3.5 and 5.5 million years ago, respectively. Our
      phylogeny reveals signatures of hybridization including incongruence between the
      plastid and nuclear gene trees, geographic clustering of the maternal (i.e.,
      plastid) lineages, and divergence ages of the nuclear gene trees consistent with
      speciation and secondary contact, respectively. CONCLUSIONS: The timing of
      speciation and ecological and morphological evolutionary events in Nomocharis are
      temporally consistent with uplift in the Qinghai-Tibetan Plateau and of the
      Hengduan Mountains 7 and 3-4 million years ago, respectively. Thus, we speculate
      that the mountain building may have provided new habitats that led to
      specialization of morphological and ecological features in Nomocharis and the
      nested Lilium along ecological gradients. Additionally, we suspect that the
      mountain building may have led to secondary contact events that enabled
      hybridization in Lilium-Nomocharis. Both the habitat specialization and
      hybridization have probably played a role in generating the striking
      morphological differences between Lilium and Nomocharis.

PMID- 26219288
TI  - Non-use of health care service among empty-nest elderly in Shandong, China: a
      cross-sectional study.
AB  - BACKGROUND: Empty-nest elderly refers to those elderly with no children or whose
      children have already left home. Few studies have focused on healthcare service
      use among empty-nest seniors, and no studies have identified the prevalence and
      profiles of non-use of healthcare services among empty-nest elderly. The purpose
      of this study is to compare the prevalence of non-use of healthcare services
      between empty-nest and non-empty-nest elderly and identify risk factors for the
      non-use of healthcare services among empty-nest seniors. METHODS: Four thousand
      four hundred sixty nine seniors (60 years and above) were draw from a cross
      sectional study conducted in three urban districts and three rural counties of
      Shandong Province in China. Non-visiting within the past 2 weeks and non
      hospitalization in previous year are used to measure non-use of healthcare
      services. Chi-square test is used to compare the prevalence of non-use between
      empty-nesters and non-empty-nesters. Multivariate logistic regression analysis is
      employed to identify the risk factors of non-use among empty-nest seniors.
      RESULTS: Of 4469 respondents, 2667 (59.7%) are empty-nesters. Overall, 35.5% of
      the participants had non-visiting and 34.5% had non-hospitalization. Non-visiting
      rate among empty-nest elderly (37.7%) is significantly higher than that among non
      empty-nest ones (32.7%) (P = 0.008). Non-hospitalization rate among empty-nesters
      (36.1%) is slightly higher than that among non-empty-nesters (31.6%) (P = 0.166).
      Financial difficulty is the leading cause for both non-visiting and non
      hospitalization of the participants, and it exerts a larger negative effect on
      access to healthcare for empty-nest elderly than non-empty-nest ones. Both non
      visiting and non-hospitalization among empty-nest seniors are independently
      associated with low-income households, health insurance status and non
      communicable chronic diseases. The non-visiting rate is also found to be higher
      among the empty-nesters with lower education and those from rural areas.
      CONCLUSIONS: Our findings indicate that empty-nest seniors have higher non-use
      rate of healthcare services than non-empty-nest ones. Financial difficulty is the
      leading cause of non-use of health services. Healthcare policies should be
      developed or modified to make them more pro-poor and also pro-empty-nested.

PMID- 26219289
TI  - A Rare Case of Azathioprine-Induced Sweet's Syndrome in a Patient with Crohn's
      Disease.
AB  - Sweet's syndrome has been reported in association with inflammatory diseases such
      as Crohn's disease. It has also been reported in association with several drugs.
      Here, we report a rare case of Sweet's syndrome induced by azathioprine in a
      patient with Crohn's disease. 

PMID- 26219290
TI  - Neurologic and Cardiovascular Complications in Pediatric Life Threatening
      Imipramine Poisoning.
AB  - We present an 18-month boy with imipramine poisoning to illustrate the neuro
      cardiac toxic effects of this potentially deadly poison in children. The toddler
      ingested an unknown amount of imipramine from a non-childproof bottle which
      clearly labelled that the drug must be kept out of reach from children. He
      developed neurologic and cardiac symptoms. Electrocardiography (ECG) showed
      tachycardia and widened QRS. He was immediately treated with bicarbonate infusion
      and made an uneventful recovery. This is the youngest and only reported case of
      symptomatic imipramine ingestion in our locality. Imipramine has been surpassed
      by newer antidepressants for the treatment of depression in the past decade.
      Literature is searched to review the mortality rate in young children. Intensive
      care neuro-cardiac support contributes to the favorable outcome. Despite clear
      labelling of the bottle, carelessness on the part of the adult and the use of non
      childproof bottle are definite preventable factor to such potentially fatal
      ingestion. 

PMID- 26219291
TI  - The Role of Disproportionality Analysis of Pharmacovigilance Databases in Safety
      Regulatory Actions: a Systematic Review.
AB  - INTRODUCTION: Disproportionality analysis (DA) of adverse drug reactions
      spontaneous reporting (SR) databases is used to identify signals of
      disproportionate reporting (SDR). The objective of this study was to identify the
      generation of SDR in the published literature and whether it led to regulatory
      action. METHODS: A systematic literature search in MEDLINE and Cochrane Central
      Register for Controlled Trials (CENTRAL) in a 10-year period, from 2005 to 2014,
      was conducted, to identify studies designed to detect drug safety signals through
      the use of disproportionality measures applied to spontaneous reporting databases
      of adverse drug reactions. RESULTS: Seventy three studies were included. The
      number of publications has been rising over the study time period. Forty nine
      studies focus on drug-event combinations. Large international and smaller
      national or regional databases were identified. The disproportionality measures
      applied included frequentist and Bayesian methods and some studies used more than
      one method. SDRs were identified in more than ninety percent of the studies. Ten
      studies were found to be confirmatory of previous regulatory decision.
      CONCLUSION: It was not found any safety signal issued by drug regulatory agencies
      exclusively generated by DA. More research devoted to this issue is needed, since
      the value of these methods on drug safety signaling and their impact on drug
      regulation actions remains to be established.

PMID- 26219292
TI  - Rare manifestations of infective endocarditis: the long known, never to be
      forgotten diagnosis.
AB  - Infective endocarditis (IE) is a life-threatening condition often manifesting as
      a multisystem disease; its heterogeneous features present a diagnostic challenge.
      We report two cases of IE masquerading as rare extracardiac complications: a
      splenectomised patient with a periarticular ankle abscess and acute
      encephalopathy; and a young man with a cutaneous vasculitis following a
      spontaneous intracerebral haemorrhage. In both cases, the diagnosis was suspected
      following detection of afebrile bacteraemia and confirmed with echocardiography.
      Risk factors included a pneumococcal bacteraemia in the asplenic patient and a
      previously undiagnosed bicuspid aortic valve in the second patient. Both patients
      recovered well with appropriate antibiotic therapy followed by valve surgery. IE
      is an important diagnosis to consider in patients with systemic symptoms or organ
      specific, otherwise unexplained relevant pathology especially in the presence of
      a cardiac murmur or risk factors for IE including structural heart disease,
      prosthetic valves or intravascular devices, and in immunosuppressed patients. 

PMID- 26219293
TI  - Acute coronary syndrome and depression: A review of shared pathophysiological
      pathways.
AB  - OBJECTIVE: To examine the evidence for shared pathophysiological pathways in
      acute coronary syndrome and major depression and to conceptualise the dynamic
      interplay of biological systems and signalling pathways that link acute coronary
      syndrome and depression within a framework of neuro-visceral integration.
      METHODS: Relevant articles were sourced via a search of published literature from
      MEDLINE, EMBASE and PubMed using a variety of search terms relating to biological
      connections between acute coronary syndrome and depression. Additional articles
      from bibliographies of retrieved papers were assessed and included where
      relevant. RESULTS: Despite considerable research efforts, a clear understanding
      of the biological processes connecting acute coronary syndrome and depression has
      not been achieved. Shared abnormalities are evident across the immune,
      platelet/endothelial and autonomic/stress-response systems. From the available
      evidence, it seems unlikely that a single explanatory model could account for the
      complex interactions of biological pathways driving the pathophysiology of these
      disorders and their comorbidity. CONCLUSION: A broader conceptual framework of
      mind-body or neuro-visceral integration that can incorporate the existence of
      several causative scenarios may be more useful in directing future research and
      treatment approaches for acute coronary syndrome-associated depression.

PMID- 26219294
TI  - Assessment of occupational safety risks in Floridian solid waste systems using
      Bayesian analysis.
AB  - Safety risks embedded within solid waste management systems continue to be a
      significant issue and are prevalent at every step in the solid waste management
      process. To recognise and address these occupational hazards, it is necessary to
      discover the potential safety concerns that cause them, as well as their direct
      and/or indirect impacts on the different types of solid waste workers. In this
      research, our goal is to statistically assess occupational safety risks to solid
      waste workers in the state of Florida. Here, we first review the related standard
      industrial codes to major solid waste management methods including recycling,
      incineration, landfilling, and composting. Then, a quantitative assessment of
      major risks is conducted based on the data collected using a Bayesian data
      analysis and predictive methods. The risks estimated in this study for the period
      of 2005-2012 are then compared with historical statistics (1993-1997) from
      previous assessment studies. The results have shown that the injury rates among
      refuse collectors in both musculoskeletal and dermal injuries have decreased from
      88 and 15 to 16 and three injuries per 1000 workers, respectively. However, a
      contrasting trend is observed for the injury rates among recycling workers, for
      whom musculoskeletal and dermal injuries have increased from 13 and four injuries
      to 14 and six injuries per 1000 workers, respectively. Lastly, a linear
      regression model has been proposed to identify major elements of the high number
      of musculoskeletal and dermal injuries. 

PMID- 26219295
TI  - Cannulation in aortic surgery: subclavian and axillary cannulation.
AB  - Cannulation of peripheral vessels is being frequently used as a standard access
      for establishing cardiopulmonary bypass (CPB) in recent times. Apart from an
      increased use in patients requiring left ventricular circulatory support, i.e.
      either extracorporeal membrane oxygenation or long-term ventricular assist device
      systems, peripheral vessel cannulation is also beneficial in aortic surgery. The
      subclavian and axillary arteries are commonly used as sites for arterial
      cannulation to establish CPB during aortic surgery in many centres. Both
      cannulation sites enable safe implementation of CPB in patients requiring complex
      and difficult reoperations and those undergoing aortic surgery for acute type A
      aortic dissections or artherosclerotic aortic disease, in which cerebral
      perfusion is required. Here, we describe our techniques of direct cannulation of
      the subclavian and axillary artery for aortic arch surgery. 

PMID- 26219296
TI  - Pre-procedural assessment of aortic annulus dimensions for transcatheter aortic
      valve replacement: comparison of a non-contrast 3D MRA protocol with contrast
      enhanced cardiac dual-source CT angiography.
AB  - AIMS: To evaluate the feasibility of a non-contrast three-dimensional (3D)-FLASH
      magnetic resonance angiography (MRA) protocol for pre-procedural aortic annulus
      assessment for transcatheter aortic valve replacement (TAVR) in comparison with
      cardiac dual-source computed tomography angiography (CTA). METHODS AND RESULTS:
      In this prospective study, 69 of 104 consecutive patients (mean age 81.8 +/- 5.4
      years, 37.7% arrhythmic) with severe aortic stenosis who had undergone pre-TAVR
      cardiac CTA received a respiratory and ECG-triggered, non-contrast 3D-FLASH MRA
      at 3 T. Annular area measurements were obtained at mid-diastole for both
      modalities whereas maximum systolic area was assessed by CTA only. Systolic MRA
      dimensions were modelled, by adding the relative difference of systolic and
      diastolic CTA area dimensions as a corrective factor. Hypothetical prosthesis
      sizing was performed based on systolic CTA, diastolic, and modelled systolic MRA
      area measurements. MR image quality and degree of annular calcifications were
      evaluated using 4-point-grading scales. The mean acquisition time was 14 +/- 4.2
      min. The mean image quality was 3.1 +/- 0.9 with only two examinations rated non
      diagnostic. The mean degree of calcifications was equal. As assessed by Bland
      Altman analysis, there was no relevant systematic difference between area
      measurements for modelled systolic MRA and systolic CTA [the mean difference -3.1
      mm(2) (limits of agreement -44.4 mm(2); 38.2 mm(2))]. Agreement for hypothetical
      prosthesis sizing was found in 63 of 67 (94%) patients for systolic CTA and
      modelled systolic MRA. CONCLUSION: The employed non-contrast 3D-FLASH MRA
      protocol allows for reliable assessment of aortic annulus dimensions and
      calcifications even in the presence of arrhythmias in an all-comers pre-TAVR
      population. Implementation of this technique appears legitimate in patients at an
      increased risk for contrast-induced nephropathy.

PMID- 26219297
TI  - Strain echocardiographic assessment of left atrial function predicts recurrence
      of atrial fibrillation.
AB  - AIMS: We evaluated if a dispersed left atrial (LA) contraction pattern was
      related to atrial fibrillation (AF) in patients with normal left ventricular (LV)
      function, and normal or mildly enlarged left atrium. METHODS AND RESULTS: We
      included 61 patients with paroxysmal AF (PAF). Of these, 30 had not while 31 had
      recurrence of AF after radiofrequency ablation (RFA). Twenty healthy individuals
      were included for comparison. Echocardiography was performed in patients in sinus
      rhythm the day before RFA. LA volume was calculated. Peak negative longitudinal
      strain was assessed in 18 LA segments during atrial systole. Contraction duration
      in 18 LA segments was measured as the time from peak of the P wave on
      electrocardiogram to maximum myocardial shortening in each segment. The standard
      deviation of contraction durations was defined as LA mechanical dispersion (LA
      MD). LA size was rather preserved in patients with PAF (LA volume 25 +/- 10
      mL/m(2)). LA MD was more pronounced in patients with recurrence of AF after RFA
      compared with those without recurrence and controls (38 +/- 14 ms vs. 30 +/- 12
      ms vs. 16 +/- 8 ms, both P < 0.001). LA MD was a predictor of PAF [OR 7.84 (95%CI
      2.15-28.7), P < 0.01, per 10 ms increase] adjusted for age, LA volume, e', and LA
      function. LA function by strain was reduced in both patients with and without
      recurrent AF after RFA compared with controls (-14 +/- 4% vs. -16 +/- 3% vs. -19
      +/- 2%, both P < 0.05). CONCLUSION: LA MD was pronounced, and LA deformation was
      reduced in patients with PAF with apparently normal LV structure and function,
      and normal or mildly enlarged LA. LA MD may be useful as a predictor of AF
      recurrence after RFA.

PMID- 26219298
TI  - Modeling Epistasis in Genomic Selection.
AB  - Modeling epistasis in genomic selection is impeded by a high computational load.
      The extended genomic best linear unbiased prediction (EG-BLUP) with an epistatic
      relationship matrix and the reproducing kernel Hilbert space regression (RKHS)
      are two attractive approaches that reduce the computational load. In this study,
      we proved the equivalence of EG-BLUP and genomic selection approaches, explicitly
      modeling epistatic effects. Moreover, we have shown why the RKHS model based on a
      Gaussian kernel captures epistatic effects among markers. Using experimental data
      sets in wheat and maize, we compared different genomic selection approaches and
      concluded that prediction accuracy can be improved by modeling epistasis for
      selfing species but may not for outcrossing species. 

PMID- 26219300
TI  - Experiences of Pediatric Oncology Patients and Their Parents at End of Life: A
      Systematic Review.
AB  - Improvement in pediatric palliative and end-of-life care has been identified as
      an ongoing research priority. The child and parent experience provides valuable
      information to guide how health care professionals can improve the transition to
      end of life and the care provided to children and families during the vulnerable
      period. The purpose of this systematic review was to describe the experience of
      pediatric oncology patients and their parents during end of life, and identify
      gaps to be addressed with interventions. A literature search was completed using
      multiple databases, including CINAHL, PubMed, and PsycInfo. A total of 43
      articles were included in the review. The analysis of the evidence revealed 5
      themes: symptom prevalence and symptom management, parent and child perspectives
      of care, patterns of care, decision making, and parent and child outcomes of
      care. Guidelines for quality end-of-life care are needed. More research is needed
      to address methodological gaps that include the pediatric patient and their
      sibling's experience. 

PMID- 26219301
TI  - Utilization of an Intravenous Line Lifter Within a Pediatric Oncology Population.
AB  - Young children with cancer often have central lines. When ambulating during an
      intravenous infusion, their tubing drags on the hospital floor resulting in
      contamination of the exterior of the tubing. The tubing can then contaminate the
      children's linens, where central line procedures occur, increasing the risk of a
      central lineassociated blood stream infection. The purpose of this project was to
      evaluate the IV Line Lifter as a device to decrease contamination of the exterior
      of IV tubing. Baseline adenosine triphosphate bioluminescence testing was used on
      the exterior IV tubing to quantify organic matter as relative light units. The
      bioluminescence tests were performed on ambulatory, inpatient children with
      cancer ages 2 to 10 years, preimplementation (n = 29) and postimplementation (n =
      18) of the IV Line Lifter. Relative light unit levels significantly decreased
      postimplementation (P < .001). Users of the device reported ease of ambulation
      when using the device and a willingness to use again. Results support the need
      for an IV Line Lifter to keep IV tubing off of the hospital floor, to ease
      ambulation, and decrease the risk of central line-associated blood stream
      infection. 

PMID- 26219299
TI  - Longevity Genes Revealed by Integrative Analysis of Isoform-Specific daf-16/FoxO
      Mutants of Caenorhabditis elegans.
AB  - FoxO transcription factors promote longevity across taxa. How they do so is
      poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms
      of the FoxO transcription factor DAF-16 extend life span in the context of
      reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate
      the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed
      an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to
      previous studies suggesting that DAF-16F plays a more prominent role in life span
      control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole
      transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in
      life span control, stress resistance, and target gene regulation. Integration of
      these datasets enabled the prioritization of a subset of 92 DAF-16/FoxO target
      genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific
      target genes significantly influenced longevity. A loss-of-function mutation in
      the conserved gene gst-20, which is induced by DAF-16A, reduced life span
      extension in the context of daf-2/IGFR RNAi without influencing longevity in
      animals subjected to control RNAi. Therefore, gst-20 promotes DAF-16/FoxO
      dependent longevity. Conversely, a loss-of-function mutation in srr-4, a gene
      encoding a seven-transmembrane-domain receptor family member that is repressed by
      DAF-16A, extended life span in control animals, indicating that DAF-16/FoxO may
      extend life span at least in part by reducing srr-4 expression. Our discovery of
      new longevity genes underscores the efficacy of our integrative strategy while
      providing a general framework for identifying specific downstream gene regulatory
      events that contribute substantially to transcription factor functions. As FoxO
      transcription factors have conserved functions in promoting longevity and may be
      dysregulated in aging-related diseases, these findings promise to illuminate
      fundamental principles underlying aging in animals. 

PMID- 26219303
TI  - Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous
      malignancies in an Ezh1-dependent manner.
AB  - Recent genome sequencing revealed inactivating mutations in EZH2, which encodes
      an enzymatic component of polycomb-repressive complex 2 (PRC2), in patients with
      myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), and MDS/MPN
      overlap disorders. We herein demonstrated that the hematopoietic-specific
      deletion of Ezh2 in mice induced heterogeneous hematopoietic malignancies.
      Myelodysplasia was detected in mice following the deletion of Ezh2, and resulted
      in the development of MDS and MDS/MPN. Thrombocytosis was induced by Ezh2 loss
      and sustained in some mice with myelodysplasia. Although less frequent, Ezh2 loss
      also induced T-cell acute lymphoblastic leukemia and the clonal expansion of B-1a
      B cells. Gene expression profiling showed that PRC2 target genes were derepressed
      upon the deletion of Ezh2 in hematopoietic stem and progenitor cells, but were
      largely repressed during the development of MDS and MDS/MPN. Chromatin
      immunoprecipitation-sequence analysis of trimethylation of histone H3 at lysine
      27 (H3K27me3) revealed a compensatory function of Ezh1, another enzymatic
      component of PRC2, in this process. The deletion of Ezh1 alone did not cause
      dysplasia or any hematologic malignancies in mice, but abolished the repopulating
      capacity of hematopoietic stem cells when combined with Ezh2 loss. These results
      clearly demonstrated an essential role of Ezh1 in the pathogenesis of
      hematopoietic malignancies induced by Ezh2 insufficiency, and highlighted the
      differential functions of Ezh1 and Ezh2 in hematopoiesis. 

PMID- 26219302
TI  - Diffusion Tensor Imaging and Neurobehavioral Outcome in Children With Brain
      Tumors Treated With Chemotherapy.
AB  - BACKGROUND: Childhood brain tumor survivors (CBTS) often experience treatment
      related neurocognitive deficits affecting quality of life (QOL), but systemic
      chemotherapy contributions to outcomes are unclear. Our objective was to relate
      brain tissue changes to neurocognitive and QOL effects after systemic
      myeloablative chemotherapy with autologous hematopoietic progenitor cell rescue
      in CBTS. PROCEDURE: Regional brain volumes and diffusion tensor indices were
      correlated with neurocognitive, behavioral, and QOL measures, and compared
      between 8 CBTS (mean age 8.5 years, mean age at diagnosis 32 months), and 9
      healthy controls (mean 9.3 years). RESULTS: Overall QOL, school, and psychosocial
      functioning were significantly lower in patients (P < .05). Most patients scored
      within normative ranges on neurocognitive and behavioral assessment. Elevated
      mean diffusivity and decreased fractional anisotropy, indicating gray and white
      matter injury, respectively, appeared in memory and executive functioning areas.
      Low scores on Inhibition on the Neuropsychological Assessment-II were correlated
      with elevated mean diffusivity in prefrontal cortex. CONCLUSIONS: Brain injury,
      decreased QOL, and to a lesser extent, executive functioning deficits appear in
      CBTS treated with myeloablative chemotherapy and autologous hematopoietic
      progenitor cell rescue. Early cognitive and psychological assessment and
      intervention are warranted in this population.

PMID- 26219309
TI  - Rapamycin alleviates pathogenesis of a new Drosophila model of ALS-TDP.
AB  - TDP-43 is a multi-functional RNA/DNA-binding protein, well-conserved among many
      species including mammals and Drosophila. However, it is also a major component
      of the pathological inclusions associated with degenerating motor neurons of
      amyotrophic lateral sclerosis (ALS). Further, TDP-43 is a signature protein in
      one subtype of frontotemporal degeneration, FTLD-U. Currently, there are no
      effective drugs for these neurodegenerative diseases. We describe the generation
      and characterization of a new fly model of ALS-TDP with transgenic expression of
      the Drosophila ortholog of TDP-43, dTDP, in adult flies under the control of a
      temperature-sensitive motor neuron-specific GAL4, thus bypassing the deleterious
      effect of dTDP during development. Diminished lifespan as well as impaired
      locomotor activities of the flies following induction of dTDP overexpression have
      been observed. Dissection of the T1/T2 region of the thoracic ganglia has
      revealed loss of these neurons. To counter the defects in this fly model of ALS
      TDP, we have examined the therapeutic effects of the autophagy activator,
      rapamycin. Although harmful to the control flies, administration of 400 MUM
      rapamycin before the induction of dTDP overexpression can significantly reduce
      the number of neurons bearing dTDP (+) aggregates, as well as partially rescue
      the diminished lifespan and locomotive defects of the ALS-TDP flies. Furthermore,
      we identify S6K, a downstream mediator of the TOR pathway, as one genetic
      modifier of dTDP. In sum, this Drosophila model of ALS-TDP under temporal and
      spatial control presents a useful new genetic tool for the screening and
      validation of therapeutic drugs for ALS. Furthermore, the data support our
      previous finding that autophagy activators including rapamycin are potential
      therapeutic drugs for the progression of neurodegenerative diseases with TDP-43
      proteinopathies. 

PMID- 26219311
TI  - In Situ Self-Sacrificed Template Synthesis of Fe-N/G Catalysts for Enhanced
      Oxygen Reduction.
AB  - To facilely prepare high-performance Fe-N/G oxygen reduction catalysts via a
      simple and controllable route from available and low-cost materials is still a
      challenge. Herein, we develop an in situ self-sacrificed template strategy to
      synthesize Fe-N/G catalysts from melamine, glucose, and FeSO4.7H2O.
      Fe/Fe3C@graphitic carbon nanocapsules are uniformly formed on the NG surface to
      create a highly opened and stable mesoporous framework structure. Furthermore,
      effectively doped N sites and high active Fe-Nx sites are synchronously
      constructed on such structures, leading to an enhanced synergistic effect for ORR
      and promising the Fe-N/G catalyst a similar catalytic activity and four-electron
      selectivity, but superior stability to commercial 30 wt % Pt/C catalysts in 0.1 M
      KOH solution under the same loading. 

PMID- 26219310
TI  - Test-retest reliability and task order effects of emotional cognitive tests in
      healthy subjects.
AB  - Little is known of the retest reliability of emotional cognitive tasks or the
      impact of using different tasks employing similar emotional stimuli within a
      battery. We investigated this in healthy subjects. We found improved overall
      performance in an emotional attentional blink task (EABT) with repeat testing at
      one hour and one week compared to baseline, but the impact of an emotional
      stimulus on performance was unchanged. Similarly, performance on a facial
      expression recognition task (FERT) was better one week after a baseline test,
      though the relative effect of specific emotions was unaltered. There was no
      effect of repeat testing on an emotional word categorising, recall and
      recognition task. We found no difference in performance in the FERT and EABT
      irrespective of task order. We concluded that it is possible to use emotional
      cognitive tasks in longitudinal studies and combine tasks using emotional facial
      stimuli in a single battery.

PMID- 26219312
TI  - Taming Antimicrobial Resistance: A national challenge.

PMID- 26219304
TI  - Targeting casein kinase II restores Ikaros tumor suppressor activity and
      demonstrates therapeutic efficacy in high-risk leukemia.
AB  - Ikaros (IKZF1) is a tumor suppressor that binds DNA and regulates expression of
      its target genes. The mechanism of Ikaros activity as a tumor suppressor and the
      regulation of Ikaros function in leukemia are unknown. Here, we demonstrate that
      Ikaros controls cellular proliferation by repressing expression of genes that
      promote cell cycle progression and the phosphatidylinositol-3 kinase (PI3K)
      pathway. We show that Ikaros function is impaired by the pro-oncogenic casein
      kinase II (CK2), and that CK2 is overexpressed in leukemia. CK2 inhibition
      restores Ikaros function as transcriptional repressor of cell cycle and PI3K
      pathway genes, resulting in an antileukemia effect. In high-risk leukemia where
      one IKZF1 allele has been deleted, CK2 inhibition restores the transcriptional
      repressor function of the remaining wild-type IKZF1 allele. CK2 inhibition
      demonstrated a potent therapeutic effect in a panel of patient-derived primary
      high-risk B-cell acute lymphoblastic leukemia xenografts as indicated by
      prolonged survival and a reduction of leukemia burden. We demonstrate the
      efficacy of a novel therapeutic approach for high-risk leukemia: restoration of
      Ikaros tumor suppressor activity via inhibition of CK2. These results provide a
      rationale for the use of CK2 inhibitors in clinical trials for high-risk
      leukemia, including cases with deletion of one IKZF1 allele. 

PMID- 26219313
TI  - Growth and obesity status of children from the middle socioeconomic group in
      Lucknow, northern India: A comparison with studies on children from the upper
      socioeconomic group.
AB  - BACKGROUND: Children from the upper socioeconomic group in India currently show a
      modest positive secular trend in height, accompanied by a high prevalence of
      obesity. We examined the anthropometric pattern among children from the middle
      socioeconomic group. METHODS: A cross-sectional study of anthropometry in 3794
      schoolchildren from the middle socioeconomic group in the city of Lucknow, Uttar
      Pradesh, India. RESULTS: A comparison with the data of a 20-year-old study of
      children from the upper socioeconomic group showed that the height of boys in our
      study was at par with or higher than that of boys of the same (Lucknow-Allahabad
      Varanasi) region or national data, at all centiles. In contrast, girls in our
      study were shorter than national data at all centiles and shorter than girls of
      the same region at the 3rd centile. Children from the middle socioeconomic group
      did not show the large increase in weight centiles seen in the recent data of the
      upper socioeconomic group. The values of body mass index at the 85th and 95th
      percentile at 17 or 18 years of age in girls and boys were 23 and 25 kg/m2,
      respectively. Obesity was prevalent in 1% of children of the middle socioeconomic
      group and an additional 5.7% were overweight. CONCLUSIONS: Children from the
      middle socioeconomic group in Lucknow have grown taller than their 20-year-old
      counterparts from the upper socioeconomic group. Boys have fared better than
      girls. Children from the middle socioeconomic group in Lucknow are at present
      spared from the epidemic of obesity.

PMID- 26219314
TI  - Acute transfusion reactions encountered in patients at a tertiary care centre in
      Punjab.
AB  - BACKGROUND: Blood transfusion is a life-saving procedure, which can occasionally
      be unsafe and result in a spectrum of adverse events. We aimed to determine the
      characteristics and type of acute transfusion reactions occurring in patients at
      a tertiary care centre. METHODS: A retrospective study was conducted at the
      Department of Immunohaematology and Blood Transfusion, Dayanand Medical College
      and Hospital, Ludhiana, Punjab. All acute transfusion reactions reported to the
      department from 1 Jan 2012 to 31 March 2013 were evaluated. All the adverse
      reactions were recorded, analysed and classified on the basis of their clinical
      features and laboratory tests. RESULTS: During the study period, 45 092 blood
      components were issued from the department and 190 transfusion reactions (0.42%)
      were reported. The most frequent were febrile non-haemolytic transfusion
      reactions (54.2%) followed by allergic reactions (36.3%), haemolytic reactions
      (1%) and non-specific reactions (8.5%). CONCLUSION: Each transfusion has to be
      monitored carefully with prompt recognition and treatment of acute transfusion
      reactions to decrease transfusion-related morbidity and mortality. Data from a
      well-functioning haemovigilance system can be used as a quality indicator for
      monitoring blood transfusion safety and contribute to evidence-based transfusion
      medicine.

PMID- 26219315
TI  - Surgical manifestations of scrub typhus: A diagnostic dilemma.
AB  - BACKGROUND: Scrub typhus, a zoonosis caused by Orientia tsutsugamushi, is a
      systemic febrile illness. The disease presents with diverse clinical
      manifestations, ranging from subclinical disease to multiorgan failure and fatal
      disease. It may rarely present as an acute abdomen which may lead to a diagnostic
      dilemma. We describe two serologically confirmed cases of scrub typhus presenting
      as acute abdomen-one mimicking acute appendicitis and the other acute
      cholecystitis, both managed non-operatively. A high index of suspicion, along
      with subtle indicators in the history and clinical examination help avoid
      unnecessary surgery in such cases.

PMID- 26219316
TI  - Vaccines for fungal infections.
AB  - High morbidity and mortality caused by mycotic infections has been a cause for
      concern. Trials for various vaccines against fungal pathogens have not been
      approved by the US Food and Drugs Administration because of the high cost of
      production and lack of a single suitable candidate. Most fungal infections
      require cell-mediated immunity for their clearance. This has been the basis for
      the development of various vaccines. We discuss the various trials of candidate
      vaccines, the protective efficacy as well as their shortcomings. Recent research
      suggests that a universal vaccine can be prepared which may be effective against
      most fungal pathogens. 

PMID- 26219317
TI  - Goal-directed resuscitation in sepsis: The game continues but the goalposts have
      been removed.

PMID- 26219318
TI  - The challenge of medical diagnosis: A primer on principles, probability, process
      and pitfalls.
AB  - Arriving at a medical diagnosis is a complex process, which requires clinical
      skill. However, the need for clear decisions has to be balanced by an acceptance
      of the ambiguity of many clinical situations. Complex presentations often require
      probabilistic inferences rather than presumed diagnostic certainty. The demands,
      logic and process of clinical diagnosis are highlighted. The multiple aspects of
      clinical reality and the impact of gold standards, nature of evidence and
      dichotomous disease/no disease categorization are discussed. The importance of
      population characteristics and context in diagnostics and prediction are
      emphasized. The statistics of agreement, Bayesian approach, certainty and risk,
      hazards and pitfalls, common errors, audit and the influence of commercialization
      on diagnosis are addressed. There is a need to formally teach the art and science
      of medicine and to transfer clinical skill rather than hope that such skills will
      be automatically imbibed during training.

PMID- 26219319
TI  - Reforming Central Government Health Scheme into a 'Universal Health Coverage'
      model.
AB  - BACKGROUND: Universal Health Coverage (UHC) is now recognized as a goal of all
      health systems, irrespective of income levels. In the absence of a one-size
      solution, each country has to develop strategies suited to its circumstances. How
      does the Central Government Health Scheme (CGHS) stand up to the goals and global
      experience of UHC, and what can be done to make it a model? METHODS: I relied on
      publicly available documents to identify key features of UHC, and relate it to
      the architecture of and practices in CGHS. RESULTS: Combining WHO's framework of
      health systems functions with log frame approach, I constructed a 'UHC status
      tool' of key elements and expected norms of UHC. CGHS has been performing
      strongly on financing function and for the range of services covered. It has
      performed rather poorly on all other elements of UHC. I build the argument for
      continued public provision of health, as opposed to insurance, on grounds of
      cost, public good nature of outpatient care and public health services. I suggest
      and strategize a sequence of reforms in CGHS anchored in health system
      strengthening, governance and financing, comprehensive primary care and client
      participation. CONCLUSION: It is both possible and desirable to transform CGHS
      into a UHC model within the same fiscal space. Merger of finance pools of
      centrally administered health schemes is suggested as a step towards UHC in
      India.

PMID- 26219322
TI  - Letter from Bristol.

PMID- 26219320
TI  - Ramdas M. Pai.

PMID- 26219325
TI  - FDG-PET/CT imaging in hyperimmunoglobulin E syndrome.

PMID- 26219326
TI  - Concentrate on iron and folic acid along with vitamin B12.

PMID- 26219327
TI  - Authors' Reply.

PMID- 26219328
TI  - Hiccups as an unusual manifestation of tuberculosis-associated immune
      reconstitution inflammatory syndrome.

PMID- 26219329
TI  - New ministers for health in India.

PMID- 26219330
TI  - Increase in number of medical colleges, undergraduate seats and postgraduate
      seats in medicine in India.

PMID- 26219331
TI  - Improvement in mortality indices in India, though National Rural Health Mission
      (NRHM) goal yet not achieved.

PMID- 26219332
TI  - Professor K. Srinath Reddy awarded honorary Doctor of Science (Medicine) degree
      by the University of London.

PMID- 26219334
TI  - Preliminary Findings on Men's Sexual Self-Schema and Sexual Offending:
      Differences Between Subtypes of Offenders.
AB  - Available literature suggests that sexual self-schemas (i.e., cognitive
      generalizations about sexual aspects of oneself) influence sexual behavior.
      Nonetheless, there is a lack of research regarding their role in sexual
      offending. The aim of the present study was to investigate the relationship
      between the men's sexual self-schema dimensions (passionate-loving, powerful
      aggressive, and open-minded-liberal) and different types of sexual-offending
      behavior. A total of 50 rapists, 65 child molesters (21 pedophilic, 44
      nonpedophilic), and 51 nonsexual offenders answered the Men's Sexual Self-Schema
      Scale, the Brief Symptom Inventory (BSI), and the Socially Desirable Response Set
      Measure (SDRS-5). Data were analyzed using multinomial logistic regression,
      controlling for age, school education, psychological distress, and social
      desirability. Results showed that rapists as well as nonsexual offenders were
      more likely to hold the powerful-aggressive sexual self-view compared to
      pedophilic and nonpedophilic child molesters. Overall, findings seem to be
      consistent with both a sociocultural component of aggression and the general
      cognitive profile of offenders. If further research corroborates these
      preliminary findings, sexual self-concept may be integrated into a comprehensive
      multifactorial approach of offending behavior. 

PMID- 26219335
TI  - Rejuvenation by inhibiting TGF-beta1/pSmad signaling.

PMID- 26219336
TI  - Mps1-Ndc80: one interaction to rule them all.

PMID- 26219337
TI  - Plant immune receptors mimic pathogen virulence targets.

PMID- 26219338
TI  - Cyclin E/Cdk2-dependent phosphorylation of Mcl-1 determines its stability and
      cellular sensitivity to BH3 mimetics.
AB  - Cyclin E/Cdk2 kinase activity is frequently deregulated in human cancers,
      resulting in impaired apoptosis. Here, we show that cyclin E/Cdk2 phosphorylates
      and stabilizes the pro-survival Bcl-2 family protein Mcl-1, a key cell death
      resistance determinant to the small molecule Bcl-2 family inhibitors ABT-199 and
      ABT-737, mimetics of the Bcl-2 homology domain 3 (BH3). Cyclin E levels were
      elevated and there was increased association of cyclin E/Cdk2 with Mcl-1 in ABT
      737-resistant compared to parental cells. Cyclin E depletion in various human
      tumor cell-lines and cyclin E-/- mouse embryo fibroblasts showed decreased levels
      of Mcl-1 protein, with no change in Mcl-1 mRNA levels. In the absence of cyclin
      E, Mcl-1 ubiquitination was enhanced, leading to decreased protein stability.
      Studies with Mcl-1 phosphorylation mutants show that cyclin E/Cdk2-dependent
      phosphorylation of Mcl-1 residues on its PEST domain resulted in increased Mcl-1
      stability (Thr92, and Thr163) and Bim binding (Ser64). Cyclin E knock-down
      restored ABT-737 sensitivity to acquired and inherently resistant Mcl-1-dependent
      tumor cells. CDK inhibition by dinaciclib resulted in Bim release from Mcl-1 in
      ABT-737-resistant cells. Dinaciclib in combination with ABT-737 and ABT-199
      resulted in robust synergistic cell death in leukemic cells and primary chronic
      lymphocytic leukemia patient samples. Collectively, our findings identify a novel
      mechanism of cyclin E-mediated Mcl-1 regulation that provides a rationale for
      clinical use of Bcl-2 family and Cdk inhibitors for Mcl-1-dependent tumors. 

PMID- 26219340
TI  - Individual differences in rumination in healthy and depressive samples:
      association with brain structure, functional connectivity and depression.
AB  - BACKGROUND: Rumination is an important cognitive risk factor for onset and
      relapse of depression. However, no studies have employed a dimensional approach
      in investigating the neural correlates of rumination and the relationship with
      depression. METHOD: Non-clinical healthy subjects (n = 306), who completed the
      classical rumination and depression scales, were studied using voxel-based
      morphometry and regional homogeneity (ReHo). Subsequently, mediation analysis was
      conducted to examine the influence of rumination on the relationship between
      brain structure and depression. Moreover, depressive patients (n = 60) and a
      control group (n = 63) of comparable age and education were studied with regions
      of interest that were identified in the healthy individuals. RESULTS: For healthy
      individuals, regional grey-matter volume (rGMV) of dorsolateral prefrontal cortex
      (DLPFC) and parahippocampal gyrus (PHG) were positively correlated with
      rumination. In addition, rumination had a mediating effect on the relationship
      between the DLPFC and PHG and depression. Moreover, ReHo analysis showed that
      rumination had a significantly negative correlation with functional homogeneity
      of DLPFC. However, compared to the control group, depressed patients showed
      significant decrease of rGMV in the DLPFC and PHG and there was a significant
      negative correlation between DLPFC volume and depressive rumination. CONCLUSIONS:
      Increased DLPFC volume (decreased ReHo) in healthy individuals while decreased in
      depression indicated the trend of DLPFC from inefficient inhibition ('overload
      state') to impaired regulatory mechanism ('paralysis state'). This finding might
      elucidate when and why healthy individuals would develop sustained negative mood
      and depression eventually.

PMID- 26219339
TI  - A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1
      as a therapeutic target for NF2-deficient meningiomas.
AB  - Meningiomas are the most common primary intracranial adult tumor. All
      Neurofibromatosis 2 (NF2)-associated meningiomas and ~60% of sporadic meningiomas
      show loss of NF2 tumor suppressor protein. There are no effective medical
      therapies for progressive and recurrent meningiomas. Our previous work
      demonstrated aberrant activation of mTORC1 signaling that led to ongoing clinical
      trials with rapamycin analogs for NF2 and sporadic meningioma patients. Here we
      performed a high-throughput kinome screen to identify kinases responsible for
      mTORC1 pathway activation in NF2-deficient meningioma cells. Among the emerging
      top candidates were the mTORC2-specific target serum/glucocorticoid-regulated
      kinase 1 (SGK1) and p21-activated kinase 1 (PAK1). In NF2-deficient meningioma
      cells, inhibition of SGK1 rescues mTORC1 activation, and SGK1 activation is
      sensitive to dual mTORC1/2 inhibitor AZD2014, but not to rapamycin. PAK1
      inhibition also leads to attenuated mTORC1 but not mTORC2 signaling, suggesting
      that mTORC2/SGK1 and Rac1/PAK1 pathways are independently responsible for mTORC1
      activation in NF2-deficient meningiomas. Using CRISPR-Cas9 genome editing, we
      generated isogenic human arachnoidal cell lines (ACs), the origin cell type for
      meningiomas, expressing or lacking NF2. NF2-null CRISPR ACs recapitulate the
      signaling of NF2-deficient meningioma cells. Interestingly, we observe increased
      SGK1 transcription and protein expression in NF2-CRISPR ACs and in primary NF2
      negative meningioma lines. Moreover, we demonstrate that the dual mTORC1/mTORC2
      inhibitor, AZD2014 is superior to rapamycin and PAK inhibitor FRAX597 in blocking
      proliferation of meningioma cells. Importantly, AZD2014 is currently in use in
      several clinical trials of cancer. Therefore, we believe that AZD2014 may provide
      therapeutic advantage over rapalogs for recurrent and progressive meningiomas. 

PMID- 26219341
TI  - Bicycle-related hospitalizations at a Taiwanese level I Trauma Center.
AB  - BACKGROUND: This study aimed to investigate differences in injury severity and
      mortality between patients who met with bicycle or motorcycle accidents and were
      hospitalized at a Level I trauma center in Taiwan. METHODS: We performed a
      retrospective analysis of bicycle-related injuries that have been reported in the
      Trauma Registry System in order to identify and compare 699 bicyclists to 7,300
      motorcyclists who were hospitalized for treatment between January 1, 2009 and
      December 31, 2013. Statistical analyses of the injury severity, associated
      complications, and length of stay in the hospital and intensive care unit (ICU)
      were performed to compare the risk of injury of bicyclists to that of
      motorcyclists with the corresponding unadjusted odds ratios and 95 % confidence
      intervals (CIs). Adjusted odds ratios (AORs) and 95 % CIs for mortality were
      calculated by controlling for confounding variables that included age, and an
      Injury Severity Score (ISS) was calculated. RESULTS: More of the cyclists were
      under 19 years of age or over 70 than were the motorcyclists. In contrast, fewer
      bicyclists than motorcyclists wore helmets, arrived at the emergency department
      between 11 p.m. and 7 a.m., and had a positive blood alcohol concentration test.
      The bicyclists sustained significantly higher rates of injuries to the
      extremities, while motorcyclists sustained significantly higher rates of injuries
      to the head and neck, face, and thorax. Compared to motorcyclists, the bicyclists
      had significantly lower ISSs and New Injury Severity Scores, shorter length
      hospital stays, and a smaller proportion of admittance into the ICU. However, the
      bicyclists had higher AORs for in-hospital mortality (AOR: 1.2, 95 % CI: 1.16
      1.20). In terms of critical injury severity (ISS >= 25), the bicyclists had 4.4
      times (95 % CI: 1.95-9.82) the odds of mortality than motorcyclists with the same
      ISSs. CONCLUSIONS: Data analysis indicated that the bicyclists had unique injury
      characteristics including bodily injury patterns and lower ISSs, but had higher
      in-hospital mortality compared to motorcycle riders. In this study, given that
      only 9 % of bicyclists reported wearing helmets and considering the high
      mortality associated with head injury, it is possible that some bicycle riders
      underestimated the gravity of cycling accidents.

PMID- 26219342
TI  - Emerging conservation challenges and prospects in an era of offshore hydrocarbon
      exploration and exploitation.
AB  - Globally, extensive marine areas important for biodiversity conservation and
      ecosystem functioning are undergoing exploration and extraction of oil and
      natural gas resources. Such operations are expanding to previously inaccessible
      deep waters and other frontier regions, while conservation-related legislation
      and planning is often lacking. Conservation challenges arising from offshore
      hydrocarbon development are wide-ranging. These challenges include threats to
      ecosystems and marine species from oil spills, negative impacts on native
      biodiversity from invasive species colonizing drilling infrastructure, and
      increased political conflicts that can delay conservation actions. With mounting
      offshore operations, conservationists need to urgently consider some possible
      opportunities that could be leveraged for conservation. Leveraging options, as
      part of multi-billion dollar marine hydrocarbon operations, include the use of
      facilities and costly equipment of the deep and ultra-deep hydrocarbon industry
      for deep-sea conservation research and monitoring and establishing new
      conservation research, practice, and monitoring funds and environmental
      offsetting schemes. The conservation community, including conservation
      scientists, should become more involved in the earliest planning and exploration
      phases and remain involved throughout the operations so as to influence decision
      making and promote continuous monitoring of biodiversity and ecosystems. A prompt
      response by conservation professionals to offshore oil and gas developments can
      mitigate impacts of future decisions and actions of the industry and governments.
      New environmental decision support tools can be used to explicitly incorporate
      the impacts of hydrocarbon operations on biodiversity into marine spatial and
      conservation plans and thus allow for optimum trade-offs among multiple
      objectives, costs, and risks. 

PMID- 26219343
TI  - A silica-supported solid dispersion of bifendate using supercritical carbon
      dioxide method with enhanced dissolution rate and oral bioavailability.
AB  - In this study, to enhance the dissolution rate and oral bioavailability of
      bifendate, a silica-supported solid dispersion (SD) of bifendate was prepared
      using supercritical carbon dioxide (ScCO2) technology. The properties of
      bifendate-silica SD were characterized by differential scanning calorimetry
      (DSC), X-ray diffraction (X-RD) and scanning electron microscopy. The
      pharmacokinetic study was carried out in beagle dogs using commercial bifendate
      dropping pills as a reference which is a conventional SD formulation of bifendate
      and PEG6000. A novel method of Ultra Performance Convergence Chromatography
      tandem mass spectrometry (UPC(2)TM-MS/MS) method was applied to determine
      bifendate concentration in plasma. The amorphous state of bifendate in bifendate
      silica SD was revealed in X-RD and DSC when the ratios of bifendate and silica
      were 1:15 and 1:19, respectively. In vitro dissolution rate was significantly
      improved with cumulative release of 67% within 20 min relative to 8% for the
      physical mixture of bifendate and silica, and which was also higher than the
      commercial dropping pill of 52%. After storage at 75% relative humidity (RH) for
      10 d, no recrystallization was found and reduced dissolution rate was obtained
      due to the absorption of moisture. In pharmacokinetic study, Cmax and AUC0-t for
      bifendate-silica SD were 153.1 ng/ml and 979.8 ng h/ml, respectively. AUC0-t of
      bifendate-silica SDs was ~1.6-fold higher than that of the commercial dropping
      pills. These results suggest that adsorbing bifendate onto porous silica via
      ScCO2 technique could be a feasible method to enhance oral bioavailability
      together with a higher dissolution rate. 

PMID- 26219344
TI  - Challenges in improving quality in colonoscopy: timing is critical.

PMID- 26219345
TI  - Assessing the impact of NICE guidance on the prescribing of hormonal treatments
      of breast cancer in England.

PMID- 26219347
TI  - Post-Transplantation Immunoadsorption Can Be Withheld in ABO-Incompatible Kidney
      Transplant Recipients.
AB  - After ABO-incompatible kidney transplantation, postoperative plasma exchange (PE)
      or immunoadsorption (IA) is performed per protocol or depending on postoperative
      A/B-titers to prevent acute rejection. However, the need for postoperative PE or
      IA is not known. Since 2006, 30 consecutive patients received three standard
      postoperative IAs. Starting from 2009, the last 46 patients received only
      preoperative IA. Preoperative desensitization consisted of rituximab, tacrolimus,
      mycophenolate mofetil, prednisone and intravenous immunoglobulins. Antigen
      specific IA was performed pre-operatively with the Glycosorb device. Biopsy
      proven acute rejections either antibody-mediated (AMR) or mixed cellular and
      antibody-mediated (MAR) within 3 months were recorded. The postoperative titer in
      patients with postoperative IA did not exceed 1:16 (IgG 1:4 [<2-16] median and
      range). The postoperative IgG titer was not significantly different after
      abandoning postoperative IA, although three patients had titers of 1:32 and one
      patient even 1:128. Rejections tended to be more frequent in the group with
      postoperative IA: 6 AMR and 3 MAR were recorded in 30 patients, vs. 4 AMR and 1
      MAR in the 46 patients without postoperative IA (30 vs. 11%, P = 0.067). Baseline
      characteristics differed however: in the group with postoperative IA the vast
      majority had blood group O (87 vs. 52%, P = 0.003). Also, the IgG titer on the
      day of transplantation was higher (1:4 [<2-16] vs. 1:2 [<2-32], P = 0.007). All
      14 patients with AMR and MAR rejections had postoperative IgG titers <=1:16.
      Postoperative removal of A/B-antibodies can be safely removed from the ABOi
      transplantation protocol using strict preoperative criteria for antibody
      lowering. 

PMID- 26219346
TI  - Which Aspects of Professional Commitment Can Effectively Retain Nurses in the
      Nursing Profession?
AB  - PURPOSE: This study examined which aspects of professional commitment can
      effectively retain nurses in the nursing profession. DESIGN, SETTINGS, AND
      PARTICIPANTS: This study used a longitudinal design, simple random sampling, and
      two-wave data collection to survey and follow up a representative sample of 579
      nurses for 1 year in a major medical center in northern Taiwan. METHODS: Items
      measuring each aspect of professional commitment came from Meyer et al.'s scale.
      In the second wave, administrative data were culled to determine whether these
      nurses remain employed as nurses. Structural equation modeling is used to analyze
      the data. RESULTS: Analytical results indicate that continuance commitment
      predicts nurse retention in the nursing profession (path coefficient = 0.34, p <
      .01). CONCLUSIONS: Institutional efforts to improve continuance commitment (e.g.,
      improved salary structures and enhanced professional development opportunities)
      likely retain nurses in the nursing profession. CLINICAL RELEVANCE: The findings
      of this study indicate the importance of continuance intention in retaining
      nurses. Nursing managers who face staff retention issues may consider making
      efforts to improve nurse salary and employer-sponsored benefits.

PMID- 26219349
TI  - RAC1 regulate tumor necrosis factor-alpha-mediated impaired osteogenic
      differentiation of dental pulp stem cells.
AB  - Human dental pulp contains a rapidly proliferative subpopulation of precursor
      cells termed dental pulp stem cells (DPSCs) that show self-renewal and
      multilineage differentiation, including neurogenic, chondrogenic, osteogenic and
      adipogenic. We previously reported that tomuor necrosis factor-alpha (TNF-alpha)
      (10 ng/mL) triggered osteogenic differentiation of human DPSCs via the nuclear
      factor-kappaB (NF-kappaB) signaling pathway. While previous studies showed that
      cells treated with TNF-alpha at higher concentrations showed decreased osteogenic
      differentiation capability. In this study we analyze the function of TNF-alpha
      (100 ng/mL) on osteogenic differentiation of human DPSCs for the first time and
      identify the underlying molecule mechanisms. Our data revealed that TNF-alpha
      with higher concentration significantly reduced mineralization and the expression
      of bone morphogenetic protein 2 (BMP2), alkaline phosphatase (ALP) and runt
      related transcription factor 2 (RUNX2). Further, we revealed that TNF-alpha could
      suppress the osteogenic differentiation of DPSCs via increasing the expression of
      RAC1, which could activate the Wnt/beta-catenin signaling pathway and liberate
      beta-catenin to translocate into the nucleus. Genetic silencing of RAC1
      expression using siRNA restored osteogenic differentiation of DPSCs. Our findings
      may provide a potential approach to bone regeneration in inflammatory
      microenvironments.

PMID- 26219348
TI  - Self-care behavior when suffering from the common cold and health-related quality
      of life in individuals attending an annual checkup in Japan: a cross-sectional
      study.
AB  - BACKGROUND: The World Health Organization and several governments encourage
      medical self-care (including self-medication) for minor illnesses. Accordingly,
      the factors that influence self-care have received research attention, with
      socioeconomic status identified as one such predictor. Although studies have
      examined the relationship between socioeconomic status and quality of life (QOL)
      in patients suffering from respiratory allergies or chronic illnesses, the
      relationship between QOL and self-care behavior for the common cold, the most
      common illness seen in primary care, has not been examined. Therefore, we
      investigated the relationship between QOL and self-care behavior in individuals
      suffering from the common cold. METHODS: We distributed questionnaires to 499
      people who attended an annual public health checkup in Kasama city, Japan. Valid
      questionnaires were received from 398 participants (mean age = 59.0, SD = 15.8,
      range = 24-87 years; 61.4 % women). The materials included a question relating to
      typical actions taken when treating a common cold (self-care or visiting a health
      clinic), demographics, and the Short Form-8TM (SF-8TM)-an 8-item survey that
      assesses health-related quality of life (HRQOL). The association of care action
      and HRQOL were investigated using Mann-Whitney U tests with a significance level
      of p < 0.05. RESULTS: The mean scores for the Physical Functioning, Role
      Physical, Bodily Pain, Social Functioning, Role-Emotional, and Physical Component
      Summary score of the SF-8TM were significantly higher among the self-care group
      than the group that preferred visiting a clinic. CONCLUSIONS: HRQOL among
      individuals who engage in self-care when treating the common cold was observed to
      be significantly higher than among individuals who preferred to attend a health
      clinic. It is unclear whether self-care behavior affects QOL, or whether QOL
      affects self-care behavior; however, this finding highlights the importance of
      the relationship between QOL and self-care behavior. Additional studies should be
      conducted in order to investigate the direction of causality between self-care
      behaviors and QOL further.

PMID- 26219350
TI  - Pulp revascularization for immature replanted teeth: a case report.
AB  - Immature avulsed teeth are not usually treated with pulp revascularization
      because of the possibility of complications. However, this therapy has shown
      success in the treatment of immature teeth with periapical lesions. This report
      describes the case of an immature replanted tooth that was successfully treated
      by pulp revascularization. An 8-year-old boy suffered avulsion on his maxillary
      left lateral incisor. The tooth showed incomplete root development and was
      replanted after 30 minutes. After diagnosis, revascularization therapy was
      performed by irrigating the root canal and applying a calcium hydroxide paste and
      2% chlorhexidine gel for 21 days. In the second session, the intracanal dressing
      was removed and a blood clot was stimulated up to the cervical third of the root
      canal. Mineral trioxide aggregate was placed as a cervical barrier at the
      entrance of the root canal and the crown was restored. During the follow-up
      period, periapical repair, apical closure and calcification in the apical 4 mm of
      the root canal was observed. An avulsed immature tooth replanted after a brief
      extra-alveolar period and maintained in a viable storage medium may be treated
      with revascularization. 

PMID- 26219351
TI  - Prognostic relevance of LGALS3BP in human colorectal carcinoma.
AB  - BACKGROUND: A previous report has shown that LGALS3BP (also known as 90K or Mac-2
      BP) has antitumor activity in colorectal cancer (CRC) via suppression of Wnt
      signalling with a novel mechanism of ISGylation-dependent ubiquitination of beta
      catenin. The role of LGALS3BP in CRC prognosis was investigated. METHODS: The
      role of LGALS3BP on CRC progression and clinical prognosis was analyzed by
      combining cell cultures, in vitro assays, and immunohistochemistry. RESULTS:
      Silencing of LGALS3BP in HCT-116 human colon cancer cells resulted in enhanced
      beta-catenin expression that was reversed by addition of human recombinant
      LGALS3BP. Moreover, intra-tumor delivery of LGALS3BP reduced tumor growth of
      xenografts originating from LGALS3BP-silenced HCT-116 cells. Finally, in a series
      of 196 CRC patients, LGALS3BP expression in tumor tissue associated with clinical
      outcome. Patients with high LGALS3BP expression had lower risk of relapse and a
      longer overall survival time than those with low LGALS3BP expression.
      Multivariate analyses confirmed LGALS3BP expression status as the only
      independent prognostic factor of survival. CONCLUSIONS: These results provide
      evidence that low expression of LGALS3BP participates in malignant progression of
      CRC and implicates poor prognosis, highlighting its augmentation as a potential
      therapeutic approach.

PMID- 26219352
TI  - Economic costs associated with moderate and late preterm birth: a prospective
      population-based study.
AB  - OBJECTIVE: We sought to determine the economic costs associated with moderate and
      late preterm birth. DESIGN: An economic study was nested within a prospective
      cohort study. SAMPLE: Infants born between 32(+0) and 36(+6)  weeks of gestation
      in the East Midlands of England. A sample of infants born at >=37 weeks of
      gestation acted as controls. METHODS: Data on resource use, estimated from a
      National Health Service (NHS) and personal social services perspective, and
      separately from a societal perspective, were collected between birth and 24
      months corrected age (or death), and valued in pounds sterling, at 2010-11
      prices. Descriptive statistics and multivariable analyses were used to estimate
      the relationship between gestational age at birth and economic costs. MAIN
      OUTCOME MEASURES: Cumulative resource use and economic costs over the first two
      years of life. RESULTS: Of all eligible births, 1146 (83%) preterm and 1258 (79%)
      term infants were recruited. Mean (standard error) total societal costs from
      birth to 24 months were L12 037 (L1114) and L5823 (L1232) for children born
      moderately preterm (32(+0) -33(+6)  weeks of gestation) and late preterm (34(+0) 
      36(+6)  weeks of gestation), respectively, compared with L2056 (L132) for
      children born at term. The mean societal cost difference between moderate and
      late preterm and term infants was L4657 (bootstrap 95% confidence interval, 95%
      CI L2513-6803; P < 0.001). Multivariable regressions revealed that, after
      controlling for clinical and sociodemographic characteristics, moderate and late
      preterm birth increased societal costs by L7583 (L874) and L1963 (L337),
      respectively, compared with birth at full term. CONCLUSIONS: Moderate and late
      preterm birth is associated with significantly increased economic costs over the
      first 2 years of life. Our economic estimates can be used to inform budgetary and
      service planning by clinical decision-makers, and economic evaluations of
      interventions aimed at preventing moderate and late preterm birth or alleviating
      its adverse consequences. TWEETABLE ABSTRACT: Moderate and late preterm birth is
      associated with increased economic costs over the first 2 years of life.

PMID- 26219354
TI  - Evaluation of the Level of Food Safety Protection Provided by the U.S. Grade "A"
      Pasteurized Milk Ordinance and Its Associated Cooperative Grade "A" Milk Safety
      Program.
AB  - The present study was conducted to evaluate the level of food safety protection
      provided to consumers of Grade "A" milk and milk products in the United States by
      the National Conference on Interstate Milk Shipments (NCIMS) Grade "A" Milk
      Safety Program through its implementation and enforcement of the U.S. Grade "A"
      Pasteurized Milk Ordinance (PMO). The number of reported illnesses associated
      with Grade "A" milk and milk products in the United States was obtained from
      state and federal agencies and published articles. The consumption of Grade "A"
      milk and milk products in the United States was estimated from food consumption
      survey data for individuals. The level of food safety protection was measured
      quantitatively using the metric of annual illness attack rate. During a 15-year
      period (1999 through 2013), the estimated annual illness attack rate was 0.41
      reported illnesses per 1 billion exposures (estimated using person-day intake
      data) or 0.52 reported illnesses per 1 billion lb (454 million kg) of Grade "A"
      milk and milk products consumed. Food safety protection provided to consumers of
      Grade "A" milk and milk products by the NCIMS through its implementation and
      enforcement of the PMO is important given the common consumption of Grade "A"
      milk and milk products in the United States. 

PMID- 26219353
TI  - Matrix-metalloproteinase-9 is cleaved and activated by cathepsin K.
AB  - BACKGROUND: Matrix-metalloproteinases 9 (MMP-9) belongs to the class of matrix
      metalloproteinases whose main function is to degrade and remodel the
      extracellular matrix (ECM). MMP-9 has been shown to be an integral part of many
      diseases where modulation of the ECM is a key step such as cancer, osteoporosis
      and fibrosis. MMP-9 is secreted as a latent pro-enzyme that requires activation
      in the extracellular space. Therefore, identifying physiological and molecular
      contexts, which can activate MMP-9 is important. RESULTS: Acidification of
      osteoclast-conditioned media to pH 5 resulted in a fragment with a size
      corresponding to active MMP-9. Also, treatment of recombinant proMMP-9 with
      recombinant cathepsin K (CTSK) at pH 5 yielded a fragment that corresponded to
      the molecular weight of active MMP-9, and showed MMP-9 activity. This activation
      was abrogated in the presence of CTSK inhibitor indicating that CTSK was
      responsible for the activation of pro-MMP-9. Knocking down CTSK in MDA-MB-231
      cells also diminished MMP-9 activity compared to wild type control. CONCLUSIONS:
      Here we provide the first evidence that CTSK can cleave and activate MMP-9 in
      acidic environments such as seen in tumors and during bone resorption. This
      finding provides a key link between CTSK expression in tumors and bone and ECM
      remodeling, through MMP-9 activation. This novel mechanism to activate MMP-9
      through extracellular physiological changes elucidated in this study reveals a
      protease-signaling network involving CTSK and MMP-9 and provides the impetus to
      explore ECM proteases as physiological markers and pharmacological targets.

PMID- 26219355
TI  - Purple Prairie Clover (Dalea purpurea Vent) Reduces Fecal Shedding of Escherichia
      coli in Pastured Cattle.
AB  - A 3-year (2009 to 2011) grazing study was conducted to assess the effects of
      purple prairie clover (PPC; Dalea purpurea Vent) on fecal shedding of total
      Escherichia coli in cattle. Three pasture types were used in the experiment:
      bromegrass (Check), mixed cool season grasses with PPC (Simple), and mixed cool
      and warm grasses with PPC (Complex). Pastures were rotationally grazed during a
      summer and fall grazing period. PPC was grazed in summer at the vegetative or
      early flower stage and at the flower or early seed stage during the fall. Fecal
      samples were collected for enumeration of E. coli and chemical analyses. Forage
      samples were collected throughout grazing for analysis. Condensed tannins (CT)
      were only detected in Simple and Complex pastures that contained PPC, with higher
      concentrations found in the fall than in the summer. Fecal counts of E. coli in
      cattle grazing Simple and Complex pastures linearly decreased (P < 0.05) over
      summer to fall in all 3 years, an outcome not observed in cattle grazing the
      Check pasture. Across the three grazing seasons, fecal E. coli was lower (P <
      0.05) in cattle grazing Simple and Complex pastures than in those grazing the
      Check pasture during the fall. During the fall, feces collected from cattle
      grazing the Check pasture had higher (P < 0.05) values for pH, N, NH3-N, total
      volatile fatty acids, and branched-chain volatile fatty acids, but a lower (P <
      0.05) acetate:propionate ratio than feces collected from cattle grazing Simple or
      Complex pastures. In a second experiment, two strains of E. coli were cultured in
      M9 medium containing 25 to 200 MUg/ml of PPC CT. Growth of E. coli was linearly
      (P < 0.01) reduced by increasing levels of PPC CT. Scanning electron micrographs
      showed electron-dense filamentous material associated with the outer membrane of
      E. coli cells exposed to CT. Incorporation of PPC into forage reduced the fecal
      shedding of E. coli from grazing cattle, likely due to the anti-E. coli
      properties of PPC CT. 

PMID- 26219356
TI  - Antimicrobial Resistance, Extended-Spectrum beta-Lactamase Productivity, and
      Class 1 Integrons in Escherichia coli from Healthy Swine.
AB  - Administration of antimicrobials to food-producing animals increases the risk of
      higher antimicrobial resistance in the normal intestinal flora of these animals.
      The present cross-sectional study was conducted to investigate antimicrobial
      susceptibility and extended-spectrum beta-lactamase (ESBL)-producing strains and
      to characterize class 1 integrons in Escherichia coli in healthy swine in
      Thailand. All 122 of the tested isolates had drug-resistant phenotypes. High
      resistance was found to ampicillin (98.4% of isolates), chloramphenicol (95.9%),
      gentamicin (78.7%), streptomycin (77.9%), tetracycline (74.6%), and cefotaxime
      (72.1%). Fifty-four (44.3%) of the E. coli isolates were confirmed as ESBL
      producing strains. Among them, blaCTX-M (45 isolates) and blaTEM (41 isolates)
      were detected. Of the blaCTX-M-positive E. coli isolates, 37 carried the blaCTX-M
      1 cluster, 12 carried the blaCTX-M-9 cluster, and 5 carried both clusters.
      Sequence analysis revealed blaTEM-1, blaTEM-135, and blaTEM-175 in 38, 2, and 1
      isolate, respectively. Eighty-seven (71%) of the 122isolates carried class 1
      integrons, and eight distinct drug-resistance gene cassettes with seven different
      integron profiles were identified in 43 of these isolates. Gene cassettes were
      associated with resistance to aminoglycosides (aadA1, aadA2, aadA22, or aadA23),
      trimethoprim (dfrA5, dfrA12, or dfrA17), and lincosamide (linF). Genes encoding
      beta-lactamases were not found in class 1 integrons. This study is the first to
      report ESBL-producing E. coli with a class 1 integron carrying the linF gene
      cassette in swine in Thailand. Our findings confirm that swine can be a reservoir
      of ESBL-producing E. coli harboring class 1 integrons, which may become a
      potential health risk if these integrons are transmitted to humans. Intensive
      analyses of animal, human, and environmental isolates are needed to control the
      spread of ESBL-producing E. coli strains. 

PMID- 26219357
TI  - When Are Qualitative Testing Results Sufficient To Predict a Reduction in
      Illnesses in a Microbiological Food Safety Risk Assessment?
AB  - Process models that include the myriad pathways that pathogen-contaminated food
      may traverse before consumption and the dose-response function to relate exposure
      to likelihood of illness may represent a "gold standard" for quantitative
      microbial risk assessment. Nevertheless, simplifications that rely on measuring
      the change in contamination occurrence of a raw food at the end of production may
      provide reasonable approximations of the effects measured by a process model. In
      this study, we parameterized three process models representing different product
      pathogen pairs (i.e., chicken-Salmonella, chicken-Campylobacter, and beef-E. coli
      O157:H7) to compare with predictions based on qualitative testing of the raw
      product before consideration of mixing, partitioning, growth, attenuation, or
      dose-response processes. The results reveal that reductions in prevalence
      generated from qualitative testing of raw finished product usually underestimate
      the reduction in likelihood of illness for a population of consumers. Qualitative
      microbial testing results depend on the test's limit of detection. The negative
      bias is greater for limits of detection that are closer to the center of the
      contamination distribution and becomes less as the limit of detection is moved
      further into the right tail of the distribution. Nevertheless, a positive bias
      can result when the limit of detection refers to very high contamination levels.
      Changes in these high levels translate to larger consumed doses for which the
      slope of the dose-response function is smaller compared with the larger slope
      associated with smaller doses. Consequently, in these cases, a proportional
      reduction in prevalence of contamination results in a less than proportional
      reduction in probability of illness. The magnitudes of the biases are generally
      less for nonscalar (versus scalar) adjustments to the distribution. 

PMID- 26219358
TI  - Role of Cellulose and Colanic Acid in Attachment of Shiga Toxin-Producing
      Escherichia coli to Lettuce and Spinach in Different Water Hardness Environments.
AB  - This study investigated the role of extracellular cellulose production by Shiga
      toxin-producing Escherichia coli (STEC) on attachment to lettuce and spinach in
      different water hardness environments. Two cellulose-producing wild-type STEC
      strains, 19 (O5:H-) and 49 (O103:H2), and their cellulose-deficient derivatives
      were used. Strain 49 also produced colanic acid as a constituent of its
      extracellular polymeric substances. Attached cells were determined by plate
      counts on the surface and cut edge of the leaves after an attachment period of 2
      h at 4 degrees C. Hydrophobicity and surface charge of the cells were determined.
      Strain 49 attached at levels 0.3 and 0.6 log greater to the surface and 0.9 and
      0.4 log greater to the cut edges of spinach compared to strain 19 for both wild
      type and cellulose-deficient cells (P > 0.05). Cellulose-producing cells attached
      more to the surface of lettuce but not of spinach than did cellulose-deficient
      cells. However, more cellulose-deficient cells attached (at levels 0.66 and 0.3
      log greater) to the cut edge of lettuce (representing damaged tissue) than did
      cellulose-proficient cells (P > 0.05). Colanic acid production was associated
      with cell surfaces of low hydrophobicity. There was a decreasing level of
      attachment for the colanic acid-producing strain when water hardness increased
      from 200 to 1,000 pm on lettuce and spinach leaf surfaces, but no effects were
      seen for other cells. This decreased attachment was associated with a more
      negative surface charge. Cells that produced colanic acid were less hydrophobic
      and exhibited greater attachment to the surface and cut edge of spinach when
      compared to cells that did not produce colanic acid. Attachment of colanic acid
      producing cells to leafy green surfaces was enhanced in higher water hardness
      environments. These data indicate that attachment of E. coli O157:H7 to leafy
      greens involves multiple mechanisms that are influenced by the type of leafy
      green, damage to the leaf, and the water hardness environment. 

PMID- 26219359
TI  - Determination of the Thermal Inactivation Kinetics of Listeria monocytogenes,
      Salmonella enterica, and Escherichia coli O157:H7 and non-O157 in Buffer and a
      Spinach Homogenate.
AB  - Produce has been associated with a rising number of foodborne illness outbreaks.
      While much produce is consumed raw, some is treated with mild heat, such as
      blanching or cooking. The objectives of this research were to compare the thermal
      inactivation kinetics of Listeria monocytogenes, Salmonella enterica, Shiga toxin
      producing Escherichia coli (STEC) O157:H7, and non-O157 STEC in phosphate
      buffered saline (PBS; pH 7.2) and a spinach homogenate and to provide an estimate
      of the safety of mild heat processes for spinach. Five individual strains of S.
      enterica, L. monocytogenes, STEC O157:H7, and non-O157 STEC were tested in PBS in
      2-ml glass vials, and cocktails of the organisms were tested in blended spinach
      in vacuum-sealed bags. For Listeria and Salmonella at 56 to 60 degrees C, D
      values in PBS ranged from 4.42 +/- 0.94 to 0.35 +/- 0.03 min and 2.11 +/- 0.14 to
      0.16 +/- 0.03 min, respectively. D-values at 54 to 58 degrees C were 5.18 +/-
      0.21 to 0.53 +/- 0.04 min for STEC O157:H7 and 5.01 +/- 0.60 to 0.60 +/- 0.13 min
      for non-O157 STEC. In spinach at 56 to 60 degrees C, Listeria D-values were 11.77
      +/- 2.18 to 1.22 +/- 0.12 min and Salmonella D-values were 3.51 +/- 0.06 to 0.47
      +/- 0.06 min. D-values for STEC O157:H7 and non-O157 STEC were 7.21 +/- 0.17 to
      1.07 +/- 0.11 min and 5.57 +/- 0.38 to 0.99 +/- 0.07 min, respectively, at 56 to
      60 degrees C. In spinach, z-values were 4.07 +/- 0.16, 4.59 +/- 0.26, 4.80 +/-
      0.92, and 5.22 +/- 0.20 degrees C for Listeria, Salmonella, STEC O157:H7, and non
      O157 STEC, respectively. Results indicated that a mild thermal treatment of
      blended spinach at 70 degrees C for less than 1 min would result in a 6-log
      reduction of all pathogens tested. These findings may assist the food industry in
      the design of suitable mild thermal processes to ensure food safety. 

PMID- 26219360
TI  - Postharvest Survival of Porcine Sapovirus, a Human Norovirus Surrogate, on
      Phytopathogen-Infected Leafy Greens.
AB  - Leafy greens are increasingly being recognized as an important vehicle for human
      noroviruses (HuNoV), which cause recurring gastroenteritis outbreaks. Leafy
      greens often become infected by phytopathogens in the field, which may cause
      symptoms on the edible parts. Whether plant pathogen infections enhance the
      survival of HuNoV on leafy greens is unknown. Lettuce and spinach plants were
      infected with a bacterium, Xanthomonas campestris pv. vitians strain 701a, and
      with Cucumber mosaic virus strain Fny, respectively. The survival rate of porcine
      sapovirus (SaV), a HuNoV surrogate, on infected and noninfected postharvest
      leaves was then assessed. In addition, acibenzolar-S-methyl, a commercial
      chemical elicitor of plant systemic defense, was used to assess whether
      stimulating the plant host defense affects the postharvest survival of SaV.
      Leaves harvested from control and treated plants were inoculated with SaV and
      incubated for 7 days at 4 degrees C. The infectivity (tissue culture infectious
      dose affecting 50% of the culture [TCID50]/ml) and RNA (genomic equivalent/ml)
      titers of SaV were assayed using immunohistochemistry staining and SaV-specific
      TaqMan real-time reverse transcription PCR. Our results showed that cucumber
      mosaic virus Fny induced mild, nonnecrotic symptoms on spinach leaves and had no
      effect on SaV survival. In contrast, X. campestris pv. vitians 701a induced small
      localized necrotic lesions and significantly enhanced SaV survival on lettuce
      leaves. Treatment with acibenzolar-S-methyl was effective in reducing X.
      campestris pv. vitians 701a-induced lesions on infected lettuce plants but had no
      direct effect on SaV survival when used on healthy lettuce plants. These findings
      indicate that phytopathogen-induced necrotic lesions may enhance the postharvest
      survival of HuNoV on lettuce leaves. Therefore, preventive measures aiming to
      maintain healthy plants and minimize preharvest biological damage are expected to
      improve the safety of leafy greens. 

PMID- 26219361
TI  - Distribution and Molecular Characterization of Salmonella enterica Hypermutators
      in Retail Food in China.
AB  - Hypermutable pathogens can easily acquire mutation opportunities, as well as
      antimicrobial resistance, and are tremendous hazards to food safety and public
      health. In this study, a total of 96 (7.6%) hypermutators were identified from
      1,264 Salmonella isolates recovered from retail foods. Pulsed-field gel
      electrophoresis analysis indicated that hypermutators were genetically diverse.
      Amino acid substitution of Val421Phe was detected in MutS in one hypermutator and
      Val246Ala in 56 other hypermutators, while no mutation in MutS was found among
      the remaining 39 hypermutators. Hypermutators in Salmonella isolates recovered in
      2010 (9.3%) and 2008 (7.7%) were significantly more prevalent than those in 2007
      (1.4%). The rate of hypermutators in mutton (22.2%) was significantly higher than
      that in chicken (7.9%) and pork (4.7%). In Salmonella Leimo isolates (60.0%),
      hypermutators were most frequently detected, followed by Salmonella Essen
      (50.0%), Salmonella Indiana (36.6%), Salmonella Kallo (25.0%), Salmonella
      Heidelberg (23.8%), Salmonella Typhimurium (14.0%), Salmonella Shubra (13.0%),
      Salmonella Albany (11.1%), Salmonella Agona (7.0%), Salmonella Gueuletapee
      (6.3%), and Salmonella Enteritidis (1.7%). Salmonella hypermutators in isolates
      recovered from retail food stored at ambient temperature (15.7%) were
      significantly more prevalent than those stored in chilled (3.1%) and frozen
      (5.4%) condition. The overall distributions of mutation frequencies of the 96
      hypermutators (selected by rifampin) were from 2.16 * 10(-5) to 4.25 * 10(-1).
      Mutation frequencies of hypermutators of Salmonella Leimo, Salmonella Essen,
      Salmonella Kallo, and Salmonella Agona were relative low, while those of
      Salmonella Typhimurium, Salmonella Indiana, and Salmonella Shubra were extremely
      high. No significant correlation was found between mutation frequency and
      antimicrobial resistance of the hypermutators. 

PMID- 26219362
TI  - Antimicrobial Activity of Cinnamaldehyde, Carvacrol, and Lauric Arginate against
      Salmonella Tennessee in a Glycerol-Sucrose Model and Peanut Paste at Different
      Fat Concentrations.
AB  - The objective of this study was to investigate the antimicrobial activities of
      carvacrol, cinnamaldehyde, and lauric arginate (LAE) against Salmonella in a low
      water activity (aw ) glycerol-sucrose model and in peanut paste with different
      fat concentrations. Salmonella Tennessee was inoculated into the model and the
      low fat (<5%) and high fat (50%) peanut paste adjusted to aw 1.0, 0.7, 0.5, and
      0.3 and with or without cinnamaldehyde, carvacrol, or LAE. The survival of the
      bacterium over 3 or 5 days at 25 degrees C was evaluated. Reduced aw alone
      decreased the viable population over time, with the highest reduction at the
      lowest aw. In the glycerol-sucrose model, all antimicrobial agents significantly
      reduced the population over time (P < 0.05) compared with the controls. LAE was
      more lethal than the essential oil components, reducing the population to
      undetectable levels by day 2 for all aw. Cinnamaldehyde was more effective than
      carvacrol at aw 0.5 and 0.3 (2.7- to 2.9-log versus 0.39- to 1.97-log reductions
      on day 3). In low-fat peanut paste, none of the antimicrobial agents inhibited
      growth of the pathogen at aw 1.0. However, inactivation was enhanced at reduced
      aw. Cinnamaldehyde and LAE both reduced the pathogen population to undetectable
      levels on day 5 at the highest concentration tested (ca. 10 times higher than
      that in the glycerol-sucrose model). Inactivation efficacy of all antimicrobial
      agents was greatly decreased but not eliminated in 50% fat peanut paste. Results
      suggest that the test antimicrobial agents were effective under low aw
      conditions, but significantly higher concentrations are needed for potential food
      applications, and fat concentration can negatively impact the efficacy of these
      antimicrobial agents. 

PMID- 26219363
TI  - Adherence Reduction of Campylobacter jejuni and Campylobacter coli Strains to HEp
      2 Cells by Mannan Oligosaccharides and a High-Molecular-Weight Component of
      Cranberry Extract.
AB  - Campylobacter infections are a leading cause of human bacterial gastroenteritis
      in the United States and are a major cause of diarrheal disease throughout the
      world. Colonization and subsequent infection and invasion of Campylobacter
      require that the bacteria adhere to the surface of host cells. Agents that
      inhibit adherence could be used prophylactically to reduce Campylobacter carriage
      and infection. Mannan oligosaccharides (MOS) have been used as a feed supplement
      in livestock animals to improve performance and to replace growth-promoting
      antibiotics. However, MOS and other nondigestible oligosaccharides may also
      prevent pathogen colonization by inhibiting adherence in the gastrointestinal
      tract. In addition, plant extracts, including those derived from cranberries,
      have been shown to have antiadherence activity against pathogens. The goal of
      this study was to assess the ability of MOS and cranberry fractions to serve as
      antiadherence agents against strains of Campylobacter jejuni and Campylobacter
      coli. Adherence experiments were performed using HEp-2 cells. Significant
      reductions in adherence of C. jejuni 29438, C. jejuni 700819, C. jejuni 3329, and
      C. coli 43485 were observed in the presence of MOS (up to 40 mg/ml) and with a
      high-molecular-weight fraction of cranberry extract (up to 3 mg/ml). However,
      none of the tested materials reduced adherence of C. coli BAA-1061. No additive
      effect in adherence inhibition was observed for an MOS-cranberry blend. These
      results suggest that both components, MOS and cranberry, could be used to reduce
      Campylobacter colonization and carriage in livestock animals and potentially
      limit human exposure to this pathogen. 

PMID- 26219364
TI  - Effect of Fill Temperature on Clostridium botulinum Type A Toxin Activity during
      the Hot Filling of Juice Bottles.
AB  - The potential threat of terrorist attacks against the United States food supply
      using neurotoxin produced by Clostridium botulinum (BoNT) has resulted in the
      need for studying the effect of various food process operations on the
      bioavailability of this toxin. The objective of this study was to evaluate C.
      botulinum type A neurotoxin bioavailability after a simulated hot fill juice
      bottling operation. C. botulinum type A acid mud toxin (~10(6) mouse lethal dose
      [MLD50]/ml) was deposited into juice bottles at an experimentally determined
      fastest cooling spot. Bottles (12 or 20 oz [355 and 592 ml]) were filled with
      either apple juice or an orange drink, at 80 or 85 degrees C, in either upright
      or inverted orientations. Toxicity of the juice was evaluated as a function of
      holding time (1 to 2 min) by the mouse bioassay. The fastest cooling point in the
      upright orientation was determined to be at a bottle's bottom rim. In the
      inverted orientation, the fastest cooling point was in the bottle cap region.
      With respect to these two points, the upright bottle cooled faster than the
      inverted bottle, which was reflected in a higher inactivation of BoNT in the
      latter. For the orange drink (pH 2.9) toxicity was reduced by 0.5 * 10(6)
      MLD50/ml to a nondetectable level after 1 min in all bottle sizes, orientations,
      and temperatures as measured by the mouse bioassay. This indicates that there was
      at least a 0.5 * 10(6) MLD50/ml reduction in activity. Inactivation in apple
      juice (pH 4.0), to the same degree as in the orange drink, was found only for the
      inverted orientation at 85 degrees C. Complete inactivation in apple juice for
      all conditions was found at a lower added toxin level of 0.25 * 10(5) MLD50/ml.
      In general, bottle inversion and filling at 85 degrees C provided complete
      inactivation of BoNT to the 0.5 * 10(6) MLD50/ml level. All experiments resulted
      in the inactivation of 2.5 * 10(4) MLD50/ml of BoNT regardless of juice type,
      fill temperature, or bottle orientation and size. 

PMID- 26219365
TI  - Assessing the Performance of Clostridium perfringens Cooling Models for Cooked,
      Uncured Meat and Poultry Products.
AB  - Heat-resistant spores of Clostridium perfringens may germinate and multiply in
      cooked meat and poultry products when the rate and extent of cooling does not
      occur in a timely manner. Therefore, six cooling models (PMP 7.0 broth model;
      PMIP uncured beef, chicken, and pork models; Smith-Schaffner version 3; and UK
      IFR ComBase Perfringens Predictor) were evaluated for relative performance in
      predicting growth of C. perfringens under dynamic temperature conditions
      encountered during cooling of cooked, uncured meat and poultry products. The
      predicted growth responses from the models were extensively compared with those
      observed in food. Data from 188 time-temperature cooling profiles (176 for single
      rate exponential cooling and 12 for dual-rate exponential cooling) were collected
      from 17 independent sources (16 peer-reviewed publications and one report) for
      model evaluation. Data were obtained for a variety of cooked products, including
      meat and poultry slurries, ground meat and poultry products with and without
      added ingredients (e.g., potato starch, sodium triphosphate, and potassium
      tetrapyrophosphate), and processed products such as ham and roast beef.
      Performance of the models was evaluated using three sets of criteria, and
      accuracy was defined within a 1- to 2-log range. The percentages of accurate,
      fail-safe, or fail-dangerous predictions for each cooling model differed
      depending on which criterion was used to evaluate the data set. Nevertheless, the
      combined percentages of accurate and fail-safe predictions based on the three
      performance criteria were 34.66 to 42.61% for the PMP 7.0 beef broth model, 100%
      for the PMIP cooling models for uncured beef, uncured pork and uncured chicken,
      80.11 to 93.18% for the Smith-Schaffner cooling model, and 74.43 to 85.23% for
      the UK IFR ComBase Perfringens Predictor model during single-rate exponential
      chilling. Except for the PMP 7.0 broth model, the other five cooling models
      (PMIP, Smith-Schaffner, and UK IFR ComBase) are useful and reliable tools that
      food processors and regulatory agencies can use to evaluate the safety of cooked
      or heat-treated uncured meat and poultry products exposed to cooling deviations
      or to develop customized cooling schedules. 

PMID- 26219366
TI  - Comparison of the Effect of Curing Ingredients Derived from Purified and Natural
      Sources on Inhibition of Clostridium perfringens Outgrowth during Cooling of Deli
      Style Turkey Breast.
AB  - The antimicrobial impact of purified and natural sources of both nitrite and
      ascorbate were evaluated against Clostridium perfringens during the postthermal
      processing cooling period of deli-style turkey breast. The objective of phase I
      was to assess comparable concentrations of nitrite (0 or 100 ppm) and ascorbate
      (0 or 547 ppm) from both purified and natural sources. Phase II was conducted to
      investigate concentrations of nitrite (50, 75, or 100 ppm) from cultured celery
      juice powder and ascorbate (0, 250, or 500 ppm) from cherry powder to simulate
      alternative curing formulations. Ground turkey breast (75% moisture, 1.2% salt,
      pH 6.2) treatments were inoculated with C. perfringens spores (three-strain
      mixture) to yield 2.5 log CFU/g. Individual 50-g portions were vacuum packaged,
      cooked to 71.1 degrees C, and chilled from 54.4 to 26.7 degrees C in 5 h and from
      26.7 to 7.2 degrees C in 10 additional hours. Triplicate samples were assayed for
      growth of C. perfringens at predetermined intervals by plating on tryptose
      sulfite-cycloserine agar; experiments were replicated three times. In phase I,
      uncured, purified nitrite, and natural nitrite treatments without ascorbate had
      5.3-, 4.2-, and 4.4-log increases in C. perfringens, respectively, at 15 h, but
      <1-log increase was observed at the end of chilling in treatments containing 100
      ppm of nitrite and 547 ppm of ascorbate from either source. In phase II, 0, 50,
      75, and 100 ppm of nitrite and 50 ppm of nitrite plus 250 ppm of ascorbate
      supported 4.5-, 3.9-, 3.5-, 2.2-, and 1.5-log increases in C. perfringens,
      respectively. In contrast, <1-log increase was observed after 15 h in the
      remaining phase II treatments supplemented with 50 ppm of nitrite and 500 ppm of
      ascorbate or >=75 ppm of nitrite and >=250 ppm of ascorbate. These results
      confirm that equivalent concentrations of nitrite, regardless of the source,
      provide similar inhibition of C. perfringens during chilling and that ascorbate
      enhances the antimicrobial effect of nitrite on C. perfringens at concentrations
      commonly used in alternative cured meats. 

PMID- 26219367
TI  - Isolation of Insecticidal Constituent from Ruta graveolens and Structure-Activity
      Relationship Studies against Stored-Food Pests (Coleoptera).
AB  - Isolates from essential oil extracted from the flowers and leaves of Ruta
      graveolens and commercial phenolic analogs were evaluated using fumigant and
      contact toxicity bioassays against adults of the stored-food pests Sitophilus
      zeamais, Sitophilus oryzae, and Lasioderma serricorne. The insecticidal activity
      of these compounds was then compared with that of the synthetic insecticide
      dichlorvos. To investigate the structure-activity relationships, the activity of
      2-isopropyl-5-methylphenol and its analogs was examined against these stored-food
      pests. Based on the 50% lethal dose, the most toxic compound against S. zeamais
      was 3-isopropylephenol, followed by 2-isopropylphenol, 4-isopropylphenol, 5
      isopropyl-2-methylphenol, 2-isopropyl-5-methylphenol, 3-methylphenol, and 2
      methylphenol. Similar results were observed with phenolic compounds against S.
      oryzae. However, when 2-isopropyl-5-methylphenol isolated from R. graveolens oil
      and its structurally related analogs were used against L. serricorne, little or
      no insecticidal activity was found regardless of bioassay. These results indicate
      that introducing and changing the positions of functional groups in the phenol
      skeleton have an important effect on insecticidal activity of these compounds
      against stored-food pests. 

PMID- 26219368
TI  - Development of Safe Food Handling Guidelines for Korean Consumers.
AB  - The purpose of this study was to develop guidelines for Korean consumers with
      regard to safe food handling practices at home by identifying current food
      handling issues. Korean consumers' behaviors regarding their safe food handling
      were identified via survey questionnaires that included items on individual
      hygiene practices, prepreparation steps when cooking, the cooking process, and
      the storage of leftover foods. The subjects were 417 Korean parents with
      elementary school children living in Seoul and Gyeonggi Province in the central
      area of Korea. The survey results revealed gaps between the knowledge or
      practices of Korean consumers and scientific evidence pertaining to safe food
      handling practices. Based on these findings, a leaflet on safe food handling
      guidelines was developed in accordance with Korean food culture. These guidelines
      suggest personal hygiene practices as well as fundamental principles and
      procedures for safe food handling from the stage of food purchase to that of
      keeping leftover dishes. A pilot application study with 50 consumers revealed
      that the guidelines effectively improved Korean consumers' safe food handling
      practices, suggesting that they can serve as practical educational material
      suitable for Korean consumers. 

PMID- 26219369
TI  - Prevalence of Escherichia coli O157:H7 and Salmonella on Inshell California
      Walnuts.
AB  - Inshell walnuts collected from California walnut handlers over four harvests were
      evaluated for the presence of Escherichia coli O157:H7 and Salmonella. E. coli
      O157:H7 was not detected in any of 2,903 375-g samples evaluated in 2011, 2012,
      and 2013 (<0.034% prevalence; 95% confidence interval [CI], 0 to 0.13%).
      Salmonella was not isolated from any of the 935 samples in 2010 (100 g evaluated;
      <0.11% prevalence; 95% CI, 0 to 0.41%) but was isolated from 2 of 905 (375 g;
      0.22% prevalence; 95% CI, 0.061 to 0.80%), 1 of 998 (375 g; 0.10% prevalence; 95%
      CI, 0.018 to 0.56%), and 1 of 1,000 (375 g; 0.10% prevalence; 95% CI, 0.018 to
      0.56%) samples in 2011, 2012, and 2013, respectively, for an average annual
      prevalence of 0.14% (375 g; 95% CI, 0.054 to 0.35%). The levels of Salmonella in
      positive samples determined by a modified most-probable-number (MPN) method were
      estimated to be 0.32 to 0.42 MPN/100 g (95% CI, 0.045 to 3.6 MPN/100 g). 

PMID- 26219370
TI  - Sequence of Colonization Determines the Composition of Mixed Biofilms by
      Escherichia coli O157:H7 and O111:H8 Strains.
AB  - Bacterial biofilms are one of the potential sources of cross-contamination in
      food processing environments. Shiga toxin-producing Escherichia coli (STEC)
      O157:H7 and O111:H8 are important foodborne pathogens capable of forming
      biofilms, and the coexistence of these two STEC serotypes has been detected in
      various food samples and in multiple commercial meat plants throughout the United
      States. Here, we investigated how the coexistence of these two STEC serotypes and
      their sequence of colonization could affect bacterial growth competition and
      mixed biofilm development. Our data showed that E. coli O157:H7 strains were able
      to maintain a higher cell percentage in mixed biofilms with the co-inoculated
      O111:H8 companion strains, even though the results of planktonic growth
      competition were strain dependent. On solid surfaces with preexisting biofilms,
      the sequence of colonization played a critical role in determining the
      composition of the mixed biofilms because early stage precolonization
      significantly affected the competition results between the E. coli O157:H7 and
      O111:H8 strains. The precolonizer of either serotype was able to outgrow the
      other serotype in both planktonic and biofilm phases. The competitive
      interactions among the various STEC serotypes would determine the composition and
      structure of the mixed biofilms as well as their potential risks to food safety
      and public health, which is largely influenced by the dominant strains in the
      mixtures. Thus, the analysis of mixed biofilms under various conditions would be
      of importance to determine the nature of mixed biofilms composed of multiple
      microorganisms and to help implement the most effective disinfection operations
      accordingly. 

PMID- 26219371
TI  - Promising Nucleic Acid Lateral Flow Assay Plus PCR for Shiga Toxin-Producing
      Escherichia coli.
AB  - Shiga toxin (Stx)-producing Escherichia coli (STEC) is a frequent cause of
      foodborne infections, and methods for rapid and reliable detection of STEC are
      needed. A nucleic acid lateral flow assay (NALFA) plus PCR was evaluated for
      detecting STEC after enrichment. When cell suspensions of 45 STEC strains, 14 non
      STEC strains, and 13 non-E. coli strains were tested with the NALFA plus PCR, all
      of the STEC strains yielded positive results, and all of the non-STEC and non-E.
      coli strains yielded negative results. The lower detection limit for the STEC
      strains ranged from 0.1 to 1 pg of genomic DNA (about 20 to 200 CFU) per test,
      and the NALFA plus PCR was able to detect Stx1- and Stx2-producing E. coli
      strains with similar sensitivities. The ability of the NALFA plus PCR to detect
      STEC in enrichment cultures of radish sprouts, tomato, raw ground beef, and beef
      liver inoculated with 10-fold serially diluted STEC cultures was comparable to
      that of a real-time PCR assay (at a level of 100 to 100,000 CFU/ml in enrichment
      culture). The bacterial inoculation test in raw ground beef revealed that the
      lower detection limit of the NALFA plus PCR was also comparable to that obtained
      with a real-time PCR assay that followed the U.S. Department of Agriculture
      guidelines. Although further evaluation is required, these results suggest that
      the NALFA plus PCR is a specific and sensitive method for detecting STEC in a
      food manufacturing plant. 

PMID- 26219372
TI  - Differential Gene Expression of Three Gene Targets among Persistent and
      Nonpersistent Listeria monocytogenes Strains in the Presence or Absence of
      Benzethonium Chloride.
AB  - Persistence of Listeria monocytogenes strains in food processing environments
      remains relatively common but is difficult to control. Understanding the basis
      for such persistence represents an important step in the potential control or
      eradication of this pathogen from these environments. In this study, reverse
      transcription PCR was used to determine the relative and absolute expression of
      selected gene targets (pocR, eutJ, and qacH) among five persistent and four
      presumed nonpersistent L. monocytogenes strains. The quantification of these
      genes as markers for the persistent phenotype and the effect of benzethonium
      chloride (BZT) on their expression was investigated. Although no markers
      correlated with the ability of strains to persist in food processing facilities
      were found, expression of pocR was upregulated in three of the five persistent
      strains, in contrast to the four presumed nonpersistent strains, which showed
      down-regulation of this gene. These results provide further knowledge of the
      differential expression of genes of persistent and presumed nonpersistent strains
      of L. monocytogenes grown in the presence or absence of BZT and identifies
      upregulation of pocR as a potential response of persistent strains of L.
      monocytogenes to exposure to BZT. 

PMID- 26219373
TI  - Effects of Dry Storage and Resubmersion of Oysters on Total Vibrio vulnificus and
      Total and Pathogenic (tdh+/trh+) Vibrio parahaemolyticus Levels.
AB  - Vibrio vulnificus (Vv) and Vibrio parahaemolyticus (Vp) are the two leading
      causes of bacterial illnesses associated with raw shellfish consumption. Levels
      of these pathogens in oysters can increase during routine antifouling aquaculture
      practices involving dry storage in ambient air conditions. After storage, common
      practice is to resubmerge these stored oysters to reduce elevated Vv and Vp
      levels, but evidence proving the effectiveness of this practice is lacking. This
      study examined the changes in Vv and in total and pathogenic (thermostable direct
      hemolysin gene and the tdh-related hemolysin gene, tdh+ and trh+) Vp levels in
      oysters after 5 or 24 h of dry storage (28 to 32 degrees C), followed by
      resubmersion (27 to 32 degrees C) for 14 days. For each trial, replicate oyster
      samples were collected at initial harvest, after dry storage, after 7 days, and
      after 14 days of resubmersion. Oysters not subjected to dry storage were
      collected and analyzed to determine natural undisturbed vibrio levels (background
      control). Vibrio levels were measured using a most-probable-number enrichment
      followed by real-time PCR. After storage, vibrio levels (excluding tdh+ and trh+
      Vp during 5-h storage) increased significantly (P < 0.001) from initial levels.
      After 7 days of resubmersion, Vv and total Vp levels (excluding total Vp in
      oysters stored for 5 h) were not significantly different (P < 0.1) from levels in
      background oysters. Vv and total and pathogenic Vp levels were not significantly
      different (P > 0.1) from levels in background oysters after 14 days of
      resubmersion, regardless of dry storage time. These data demonstrate that oyster
      resubmersion after dry storage at elevated ambient temperatures allows vibrio
      levels to return to those of background control samples. These results can be
      used to help minimize the risk of Vv and Vp illnesses and to inform the oyster
      industry on the effectiveness of routine storing and resubmerging of aquaculture
      oysters. 

PMID- 26219374
TI  - Identification of a New Tetracycline Resistance Determinant tet47 from Fish
      Intestine.
AB  - To better understand food safety risks, functional genomic analysis was conducted
      to identify undescribed antibiotic resistance genes in fish samples from an
      aquaculture fish farm in Ohio. A fosmid genomic library from pooled DNA of
      antibiotic-resistant isolates was used to screen for resistance genes against
      tetracycline (Tet). A new Tet-resistant determinant designated as tet 47 was
      identified, with the original hosts being Providencia spp. from fish intestine.
      The new gene was also found to confer Tet resistance in Escherichia coli. Fish
      and byproducts were shown to be possible carriers that may disseminate new,
      functional, and potentially transmissible antibiotic resistance determinants
      through food, feed, and environmental contacts. 

PMID- 26219375
TI  - Inactivation of Human Norovirus and Its Surrogates on Alfalfa Seeds by Aqueous
      Ozone.
AB  - Alfalfa sprouts have been associated with numerous foodborne outbreaks. Previous
      studies investigated the effectiveness of aqueous ozone on bacterially
      contaminated seeds, yet little is known about the response of human norovirus
      (huNoV). This study assessed aqueous ozone for the disinfection of alfalfa seeds
      contaminated with huNoV and its surrogates. The inactivation of viruses without a
      food matrix was also investigated. Alfalfa seeds were inoculated with huNoV
      genogroup II, Tulane virus (TV), and murine norovirus (MNV); viruses alone or
      inoculated on seeds were treated in deionized water containing 6.25 ppm of
      aqueous ozone with agitation at 22 degrees C for 0.5, 1, 5, 15, or 30 min. The
      data showed that aqueous ozone resulted in reductions of MNV and TV infectivity
      from 1.66 +/- 1.11 to 5.60 +/- 1.11 log PFU/g seeds; for all treatment times,
      significantly higher reductions were observed for MNV (P < 0.05). Viral genomes
      were relatively resistant, with a reduction of 1.50 +/- 0.14 to 3.00 +/- 0.14 log
      genomic copies/g seeds; the reduction of TV inoculated in water was similar to
      that of huNoV, whereas MNV had significantly greater reductions in genomic copies
      (P < 0.05). Similar trends were observed in ozone-treated viruses alone, with
      significantly higher levels of inactivation (P < 0.05), especially with reduced
      levels of infectivity for MNV and TV. The significant inactivation by aqueous
      ozone indicates that ozone may be a plausible substitute for chlorine as an
      alternative treatment for seeds. The behavior of TV was similar to that of huNoV,
      which makes it a promising surrogate for these types of scenarios. 

PMID- 26219376
TI  - Changes in the Content of Biogenic Amines and Fatty Acids in High Pressure
      Processed Carp Flesh (Cyprinus carpio).
AB  - Biogenic amine and fatty acid contents were determined in vacuum-packed fillets
      of common carp (Cyprinus carpio). Samples were pressure treated at 300 and 500
      MPa and were stored at 3.5 and 12 degrees C for up to 28 days (control, 0 MPa)
      and 70 days (pressure-treated). The content of eight biogenic amines (putrescine,
      cadaverine, spermidine, spermine, histamine, tyramine, tryptamine, and
      phenylethylamine) were determined. Putrescine and cadaverine were influenced by
      all factors (temperature, pressurization level, and time of storage). Tyramine
      content was the most sensitive indicator of the improper status of sample; levels
      exceeding 10 mg/kg indicated both the loss of meat freshness and temperature
      abuse, in spite of persisting good sensory indices. Neither storage temperature
      nor pressurization level had a statistically important effect on the contents of
      fatty acids. Only polyunsaturated fatty acids decreased slightly if the storage
      time exceeded 42 days. 

PMID- 26219377
TI  - Thermal Inactivation of Foodborne Enteric Viruses and Their Viral Surrogates in
      Foods.
AB  - Foodborne viruses, in particular human norovirus and hepatitis A virus, are the
      most common causes of food-associated infections and foodborne illness outbreaks
      around the world. Since it is currently not possible to cultivate human
      noroviruses and the wild-type strain of hepatitis A virus in vitro, the use of a
      variety of viral surrogates is essential to determine appropriate thermal
      processing conditions to reduce the risk associated with their contamination of
      food. Therefore, the objectives of this review are to (i) present pertinent
      characteristics of enteric foodborne viruses and their viral surrogates, (ii)
      discuss the viral surrogates currently used in thermal inactivation studies and
      their significance and value, (iii) summarize available data on thermal
      inactivation kinetics of enteric viruses, (iv) discuss factors affecting the
      efficacy of thermal treatment, (v) discuss suggested mechanisms of thermal
      inactivation, and (vi) provide insights on foodborne enteric viruses and viral
      surrogates for future studies and industrial applications. The overall goal of
      this review is to contribute to the development of appropriate thermal processing
      protocols to ensure safe food for human consumption. 

PMID- 26219378
TI  - A new allele of acid soil tolerance gene from a malting barley variety.
AB  - BACKGROUND: Acid soil is a serious limitation to crop production all over the
      world. Toxic aluminium (Al) cations in acid soil inhibit root growth and reduce
      yield. Although a gene tolerant to acid soil has been identified, it has not been
      used in malting barley breeding, which is partly due to the acid soil tolerance
      gene being linked to unfavorable malting quality traits. RESULTS: A Brazilian
      malting barley variety Br2 was identified as tolerant to acid soil. A doubled
      haploid (DH) population was developed from a cross between Br2 and the Australian
      acid-sensitive cultivar Hamelin. The DH population was tested for acid soil
      tolerance in native acid soil and a hydroponic system with pH 4.2, pH 4.2 + Al or
      pH 6.5, and genotyped using SSR, DArT and gene-specific markers. A single QTL was
      detected for all parameters related to acid soil tolerance. The QTL was mapped to
      the known HvMATE location on chromosome 4H. Sequence alignment of the HvMATE gene
      identified 13 INDELs and 87 SNPs, where one SNP coded for a single amino acid
      difference between the two varieties. A gene-specific marker was developed to
      detect the single nucleotide polymorphism between Hamelin and Br2. This marker co
      segregated with aluminium tolerance and accounted for 79 % of phenotypic
      variation for acid soil tolerance. CONCLUSION: The present study identified a
      novel source of acid soil/Al tolerance from a Brazilian malting barley cultivar
      Br2. This variety tolerated Al toxicity but was sensitive to low pH which is
      similar to most other Al-tolerant varieties. A gene-specific marker Cit7 was
      developed based on the HvMATE gene sequence. Cit7 will improve the efficiency of
      molecular-assisted selection of new barley varieties with tolerance to acid soil.
      Multiple alleles exist for the acid soil tolerance gene on chromosome 4H, so a
      malting barley variety that tolerates acid soil could be developed by selecting
      suitable tolerant alleles. Tolerance to low pH may play an important role for
      barley to adapt to acid soils.

PMID- 26219379
TI  - Glycogen storage disease type Ia (GSDIa) but not Glycogen storage disease type Ib
      (GSDIb) is associated to an increased risk of metabolic syndrome: possible role
      of microsomal glucose 6-phosphate accumulation.
AB  - BACKGROUND: In GSDIa, glucose 6-phosphate (G6P) accumulates in the endoplasmic
      reticulum (ER); in GSDIb, G6P levels are reduced in ER. G6P availability directly
      modulates the activity of 11beta-hydroxysteroid dehydrogenase type 1
      (11betaHSD1), an ER-bound enzyme playing a key role in the development of the
      metabolic syndrome (MS). OBJECTIVE: To evaluate the prevalence of MS and Insulin
      Resistance (IR) in GSDIa and GSDIb patients. PATIENTS AND METHODS: This was a
      prospective study. All the enrolled patients were followed at the Department of
      Pediatrics "Federico II" University of Naples for 10 years. Clinical and
      biochemical parameters of MS and the presence of IR were recorded. The results
      were correlated with the biochemical parameters of GSDI-related metabolic
      control. 10 GSDIa patient (median age 12.10 +/- 1.50), 7 GSDIb patients (median
      age 14.90 +/- 2.20 were enrolled in the study. They were compared to 20 and 14
      age and sex matched controls, respectively. 10 GSDIa patients (median age 24.60
      +/- 1.50) and 6 GSDIb patients (median age 25.10 +/- 2.00) completed the 10-year
      follow-up. At the end of the study the patients' data were compared to 10 and 6
      age and sex matched controls, respectively. RESULTS: At study entry, 20 % GSDIa
      patients had MS and 80 % showed 2 criteria for MS. GSDIa patients showed higher
      HOMA-IR than controls and GSDIb patients (p < 0.001, p < 0.05), respectively.
      Baseline ISI was lower in GSDIa than controls (p < 0.001). QUICKI was
      significantly lower in GSDIa than in controls (p < 0.001). At the end of the
      study 70 % of GSDIa patients had MS and 30 % showed 2 criteria for MS. HOMA-IR
      was higher in GSDIa than controls (p < 0.01). Baseline ISI was higher in GSDIb
      than controls (p < 0.005) and GSD1a (p < 0.05). QUICKI was lower in GSD1a
      patients than in controls (p < 0.03). VAI was higher in GSDIa patients than
      controls (p < 0.001) and GSDIb patients (p = 0.002). CONCLUSIONS: Our data showed
      high prevalence of IR and MS in GSDIa patients. We speculate a possible role of
      11betaHSD1 modulation by G6P availability. We suggest a routine metabolic
      assessment in GSDIa patients.

PMID- 26219380
TI  - The public health impact of malaria vaccine RTS,S in malaria endemic Africa:
      country-specific predictions using 18 month follow-up Phase III data and
      simulation models.
AB  - BACKGROUND: The RTS,S/AS01 malaria vaccine candidate recently completed Phase III
      trials in 11 African sites. Recommendations for its deployment will partly depend
      on predictions of public health impact in endemic countries. Previous predictions
      of these used only limited information on underlying vaccine properties and have
      not considered country-specific contextual data. METHODS: Each Phase III trial
      cohort was simulated explicitly using an ensemble of individual-based stochastic
      models, and many hypothetical vaccine profiles. The true profile was estimated by
      Bayesian fitting of these models to the site- and time-specific incidence of
      clinical malaria in both trial arms over 18 months of follow-up. Health impacts
      of implementation via two vaccine schedules in 43 endemic sub-Saharan African
      countries, using country-specific prevalence, access to care, immunisation
      coverage and demography data, were predicted via weighted averaging over many
      simulations. RESULTS: The efficacy against infection of three doses of vaccine
      was initially approximately 65 % (when immunising 6-12 week old infants) and 80 %
      (children 5-17 months old), with a 1 year half-life (exponential decay). Either
      schedule will avert substantial disease, but predicted impact strongly depends on
      the decay rate of vaccine effects and average transmission intensity.
      CONCLUSIONS: For the first time Phase III site- and time-specific data were
      available to estimate both the underlying profile of RTS,S/AS01 and likely
      country-specific health impacts. Initial efficacy will probably be high, but
      decay rapidly. Adding RTS,S to existing control programs, assuming continuation
      of current levels of malaria exposure and of health system performance, will
      potentially avert 100-580 malaria deaths and 45,000 to 80,000 clinical episodes
      per 100,000 fully vaccinated children over an initial 10-year phase.

PMID- 26219382
TI  - Organic base-promoted enantioselective electrophilic cyanation of beta-keto
      esters by using chiral phase-transfer catalysts.
AB  - Highly enantioselective cyanation of beta-keto esters using hypervalent
      iodine(iii) as the electrophilic cyanating reagent induced by cinchona alkaloid
      based chiral quaternary ammonium salt was demonstrated. Organic bases, especially
      DMAP, in the chiral phase-transfer catalysis were used to obtain high ees. 

PMID- 26219381
TI  - Highly stable and re-dispersible nano Cu hydrosols with sensitively size
      dependent catalytic and antibacterial activities.
AB  - Highly stable monodispersed nano Cu hydrosols were facilely prepared by an
      aqueous chemical reduction method through selecting copper hydroxide (Cu(OH)2) as
      the copper precursor, poly(acrylic acid) (PAA) and ethanol amine (EA) as the
      complexing agents, and hydrazine hydrate as the reducing agent. The size of the
      obtained Cu colloidal nanoparticles was controlled from 0.96 to 26.26 nm by
      adjusting the dosage of the copper precursor. Moreover, the highly stable nano Cu
      hydrosols could be easily concentrated and re-dispersed in water meanwhile
      maintaining good dispersibility. A model catalytic reaction of reducing p
      nitrophenol with NaBH4 in the presence of nano Cu hydrosols with different sizes
      was performed to set up the relationship between the apparent kinetic rate
      constant (kapp) and the particle size of Cu catalysts. The experimental results
      indicate that the corresponding kapp showed an obvious size-dependency.
      Calculations revealed that kapp was directly proportional to the surface area of
      Cu catalyst nanoparticles, and also proportional to the reciprocal of the
      particle size based on the same mass of Cu catalysts. This relationship might be
      a universal principle for predicting and assessing the catalytic efficiency of Cu
      nanoparticles. The activation energy (Ea) of this catalytic reaction when using
      0.96 nm Cu hydrosol as a catalyst was calculated to be 9.37 kJ mol(-1), which is
      considered an extremely low potential barrier. In addition, the synthesized nano
      Cu hydrosols showed size-dependent antibacterial activities against Pseudomonas
      aeruginosa (P. aeruginosa) and the minimal inhibitory concentration of the
      optimal sample was lower than 5.82 MUg L(-1). 

PMID- 26219383
TI  - Lysozyme adsorption in pH-responsive hydrogel thin-films: the non-trivial role of
      acid-base equilibrium.
AB  - We develop and apply a molecular theory to study the adsorption of lysozyme on
      weak polyacid hydrogel films. The theory explicitly accounts for the conformation
      of the network, the structure of the proteins, the size and shape of all the
      molecular species, their interactions as well as the chemical equilibrium of each
      titratable unit of both the protein and the polymer network. The driving forces
      for adsorption are the electrostatic attractions between the negatively charged
      network and the positively charged protein. The adsorption is a non-monotonic
      function of the solution pH, with a maximum in the region between pH 8 and 9
      depending on the salt concentration of the solution. The non-monotonic adsorption
      is the result of increasing negative charge of the network with pH, while the
      positive charge of the protein decreases. At low pH the network is roughly
      electroneutral, while at sufficiently high pH the protein is negatively charged.
      Upon adsorption, the acid-base equilibrium of the different amino acids of the
      protein shifts in a nontrivial fashion that depends critically on the particular
      kind of residue and solution composition. Thus, the proteins regulate their
      charge and enhance adsorption under a wide range of conditions. In particular,
      adsorption is predicted above the protein isoelectric point where both the
      solution lysozyme and the polymer network are negatively charged. This behavior
      occurs because the pH in the interior of the gel is significantly lower than that
      in the bulk solution and it is also regulated by the adsorption of the protein in
      order to optimize protein-gel interactions. Under high pH conditions we predict
      that the protein changes its charge from negative in the solution to positive
      within the gel. The change occurs within a few nanometers at the interface of the
      hydrogel film. Our predictions show the non-trivial interplay between acid-base
      equilibrium, physical interactions and molecular organization under nanoconfined
      conditions, which leads to non-trivial adsorption behavior that is qualitatively
      different from what would be predicted from the state of the proteins in the bulk
      solution. 

PMID- 26219385
TI  - Exploring resistance mechanisms of HCV NS3/4A protease mutations to MK5172:
      insight from molecular dynamics simulations and free energy calculations.
AB  - Mutations at a number of key positions (Ala156, Asp168 and Arg155) of the HCV
      NS3/4A protease can induce medium to high resistance to MK5172. The emergence of
      the resistant mutations seriously compromises the antiviral therapy efficacy to
      hepatitis C. In this study, molecular dynamics (MD) simulations, free energy
      calculations and free energy decomposition were used to explore the interaction
      profiles of MK5172 with the wild-type (WT) and four mutated (R155K, D168A, D168V
      and A156T) HCV NS3/4A proteases. The binding free energies predicted by Molecular
      Mechanics/Generalized Born Solvent Area (MM/GBSA) are consistent with the trend
      of the experimental drug resistance data. The free energy decomposition analysis
      shows that the resistant mutants may change the protein-MK5172 interaction
      profiles, resulting in the unbalanced energetic distribution amongst the
      catalytic triad, the strand 135-139 and the strand 154-160. Moreover, umbrella
      sampling (US) simulations were employed to elucidate the unbinding processes of
      MK5172 from the active pockets of the WT HCV NS3/4A protease and the four
      mutants. The US simulations demonstrate that the dissociation pathways of MK5172
      escaping from the binding pockets of the WT and mutants are quite different, and
      it is quite possible that MK5172 will be harder to get access to the correct
      binding sites of the mutated proteases, thereafter leading to drug resistance.

PMID- 26219386
TI  - Growth characteristics of Ti-based fumaric acid hybrid thin films by molecular
      layer deposition.
AB  - Ti-based fumaric acid hybrid thin films were successfully prepared using
      inorganic TiCl4 and organic fumaric acid as precursors by molecular layer
      deposition (MLD). The effect of deposition temperature from 180  degrees C to 350
      degrees C on the growth rate, composition, chemical state, and topology of
      hybrid films has been investigated systematically by means of a series of
      analytical tools such as spectroscopic ellipsometry, atomic force microscopy
      (AFM), high resolution X-ray photoelectron spectroscopy (XPS) and Fourier
      transform infrared spectroscopy (FTIR). The MLD process of the Ti-fumaric acid
      shows self-limiting surface reaction with a reasonable growth rate of ~0.93 A per
      cycle and small surface roughness of ~0.59 nm in root-mean-square value at 200 
      degrees C. A temperature-dependent growth characteristic has been observed in the
      hybrid films. On increasing the temperature from 180  degrees C to 300  degrees
      C, the growth rate decreases from 1.10 to 0.49 A per cycle and the XPS
      composition of the film's C : O : Ti ratio changes from 8.35 : 7.49 : 1.00 to
      4.66 : 4.80 : 1.00. FTIR spectra indicate that the hybrid films show bridging
      bonding mode at a low deposition temperature of 200  degrees C and
      bridging/bidentate mixed bonding mode at elevated deposition temperatures of 250
      and 300  degrees C. The higher C and O amounts deviating from the ideal
      composition may be ascribed to increased organic incorporation into the hybrid
      films at lower deposition temperature and temperature-dependent density of
      reactive sites (-OH). The composition of hybrid films grown at 350  degrees C
      shows a dramatic decrease in C and O elemental composition (C : O : Ti = 1.97 :
      2.76 : 1.00) due to the thermal decomposition of the fumaric acid precursor. The
      produced by-product H2O changes the structure of the hybrid films, resulting in
      the formation of more Ti-O bonds at high temperatures. The stability of the
      hybrid films against chemical and thermal treatment, and long-term storage by
      vacuum-packing was explored carefully. It is found that the ultrathin hybrid film
      can be transformed into TiO2 nanoparticles via various post deposition annealing
      processes with different topographies. Finally, the charge trapping ability of
      the hybrid film is confirmed by fabricating a charge trapping memory capacitor in
      which the hybrid film was inserted as a charge trapping layer. 

PMID- 26219387
TI  - Charge-switchable gold nanoparticles for enhanced enzymatic thermostability.
AB  - This study illustrates a facile strategy for efficient immobilization of enzymes
      on a metal nanoparticle surface. The strategy proposed here enables the enzymatic
      activity to be retained while increasing the enzyme thermostability. It is
      demonstrated that the use of a zwitterionic amino acid tyrosine as a reducing and
      capping agent to synthesise gold nanoparticles allows efficient immobilization of
      phytase enzyme through charge-switchable electrostatic interactions. The detailed
      kinetic and thermodynamic studies reveal that the proposed enzyme immobilization
      strategy improves the overall quality of phytase by reducing the activation
      energy required for substrate hydrolysis and broadening the temperature window in
      which immobilized enzyme is able to operate. The outcomes of this study indicate
      that the underlying zwitterionic nature of 20 natural amino acids along with
      significant variability in their isoelectric points and hydropathy indices as
      well the ability of some of the amino acids to reduce metal ions is likely to
      offer significant opportunities for tailoring nano-bio interfaces in a rational
      manner for a range of biological applications. 

PMID- 26219388
TI  - Ruthenium-catalyzed nucleophilic fluorination of halobenzenes.
AB  - The first pi-coordination-catalyzed nucleophilic fluorination of unactivated aryl
      halides has been demonstrated. Chlorobenzene reacts with alkali metal fluorides
      (CsF, KF) in the presence of a Cp*Ru catalyst at 120-180  degrees C to give
      fluorobenzene. 

PMID- 26219389
TI  - The Case for Development of 11-Aza-artemisinins for Malaria.
AB  - The current treatment regimens for uncomplicated malaria comprise an artemisinin
      in combination with another drug (ACT). However, the recent emergence of
      resistance to ACTs in South East Asia dramatically emphasizes the need for new
      artemisinins. The current artemisinins have been in use since the late 1970s and
      have relatively poor thermal, chemical and metabolic stabilities - all are
      metabolized or hydrolyzed in vivo to dihydroartemisinin (DHA) that itself
      undergoes facile decomposition in vivo. The current artemisinins possess
      neurotoxicity as demonstrated in animal models, an issue that mandates increased
      vigilance in view of trends to use of protracted treatment regimens involving
      sequential administration of different ACTs against the resistant disease. As
      artemisinins induce the most rapid reduction in parasitaemia of any drug, common
      sense dictates that any new artemisinin derivative, selected on the bases of more
      robust chemical and thermal stability, metabolic stability with respect to the
      generation of DHA in vivo, and relatively benign neurotoxicity should be used in
      any new ACT whose components are rationally chosen in order to counter resistant
      malaria and inhibit transmission. 11-Azaartemisinin and its N-substituted
      derivatives attract because of overall ease of preparation from artemisinin. Some
      derivatives also possess notable thermal stabilities and although metabolic
      pathways of the derivatives are as yet unknown, none can provide DHA. The
      azaartemisinins synthesized over the past 20 years are critically discussed on
      the basis of their synthetic accessibility and biological activities with the
      view to assessing suitability to serve as new artemisinin derivatives for
      treatment of malaria. 

PMID- 26219390
TI  - Small Molecules as Anti-TNF Drugs.
AB  - Tumor necrosis factor (TNF, TNF-alpha, cachectin) is a pleiotropic,
      proinflammatory cytokine with multiple biological effects, many of which are not
      yet fully understood. Although TNF was initially described as an anti-tumor agent
      more than three decades ago, current knowledge places it central to immune system
      homeostasis. TNF plays a critical role in host defense against infection, as well
      as an inhibitory role in autoimmune disease. However, TNF overproduction
      generates deleterious effects by inducing the transcription of genes involved in
      acute and chronic inflammatory responses including asthma, rheumatoid arthritis,
      Crohn's disease, and psoriasis. Direct inhibition of TNF by biologics, such as
      monoclonal antibodies and circulating TNF receptor constructs, has produced
      effective treatments for these disorders and validated the inhibition of this
      proinflammatory cytokine as an effective therapy. Unfortunately, these biological
      therapies suffer from several drawbacks, including high cost and the induction of
      autoantibody production. Thus, the development of small molecules able to
      modulate TNF production or signaling pathways remains a central challenge in
      Medicinal Chemistry. Considerable efforts have been made over the past two
      decades to develop such inhibitors, which could potentially be administered
      orally and would presumably be cheaper. This review is focused on the recent
      development of compounds that modulate the activity of this cytokine by acting at
      different levels, such as TNF expression, processing, binding to its receptors
      and direct inhibition. These approaches will be compared and discussed.

PMID- 26219391
TI  - Flavonoids, Breast Cancer Chemopreventive and/or Chemotherapeutic Agents
AB  - Flavonoids are secondary metabolites abundantly present in commonly consumed
      fruits and vegetables. They possess diverse properties such as anti-inflammatory,
      anti-oxidant and anti-cancer. Epidemiologic studies suggest that an enrich
      flavonoids diet is linked to a decreased risk of breast cancer. These protective
      properties are due to the alteration of numerous signalling pathways involved in
      cancer-related phenomena such as inflammation and proliferation. Human clinical
      trials examining the effect of supplementation of some flavonoids on disease
      prevention have been conducted. There is no natural flavonoid that has been
      approved for the treatment of breast cancer. However, natural flavonoids served
      as lead compounds in the synthesis of cancer chemopreventive and/or therapeutic
      agents.

PMID- 26219392
TI  - Chalcones as Promising Lead Compounds on Cancer Therapy.
AB  - Chalcones constitute a group of phenolic compounds that command an increasing
      interest on cancer research. Natural chalcones are widespread through the plant
      kingdom. The most abundant and investigated chalcones are isoliquiritigenin,
      flavokawain and xanthohumol, which are present in the Fabaceae, Piperaceae,
      Cannabaceae, and Moraceae families. These chalcones have been shown to be
      promising lead antitumor-chemopreventive drugs by three different activities:
      antioxidants, cytotoxic and apoptosis inducers. In the recent years, SAR
      (structure-activity relationship) has contributed towards the improvement of
      anticancer properties of chalcones by substituting aryl rings and introducing
      heterocyclic moieties. This review summarizes the anticancer activities shown by
      natural chalcones and the SAR and describes how different chemical moiety
      modifications could lead them to be therapeutically useful in the treatment of
      cancer. 

PMID- 26219393
TI  - The Pros and the Cons for the Use of Silybin-Rich Oral Formulations in Treatment
      of Liver Damage (NAFLD in Particular).
AB  - The increasing prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) worldwide
      is becoming a challenge for the modern global care system. The lipotoxic process
      is characterized by an oxidative stress followed by a burst of the inflammatory
      response, prompting the wound healing process (fibrosis), which can ultimately
      lead to the development of cirrhosis and the subsequent complications. There is
      no consensus concerning an effective pharmacological treatment. Therefore, there
      is a need for effective therapeutic compounds. Silibinin the major active
      compound of Milk Thistle may be a potential candidate mainly due to its anti
      oxidant, anti-inflammatory, and anti-fibrotic properties. In spite of the large
      number of data obtained in experimental models, the translation of the evidence
      in clinical setting is far to be conclusive. The aim of this paper is to
      critically review the aspects of the use of the different formulations of
      Silibinin in several experimental and clinical settings and to provide hints on
      the needed future studies. 

PMID- 26219394
TI  - Mitochondria-Mediated Oxidative Stress: Old Target for New Drugs.
AB  - Oxidative stress, one of the crucial factors of genomic instability, is involved
      in many illnesses - from DNA damage and repair (DDR) related diseases to
      neurological abnormalities and cancer. Patients with defective DDR pathways
      display high level of cancer predisposition and at the same time - reveal
      hydrocephalia, dementias and even diabetes mellitus - all representing common
      hallmarks of mitochondria-related disorders. Since mitochondria are responsible
      both for the cell energetic metabolism and for reactive oxygen/nitrogen species
      (RO/NS) formation, mitochondrial dysfunction (MDF) play a pivotal role in the
      above disorders. Not surprisingly, RO/NS are considered to be a primary target
      for a large spectrum of compounds aiming to eliminate these adverse species or,
      in contrary, enhance their presence in order to amplify cellular death pathways.
      Yet, only few chemicals have received medical appreciation mainly because of
      their questionable therapeutic values in healthy states. As a result, recent
      efforts have been focused on finding the drugs that improve mitochondrial
      functions or chemoprevent MDF rather than being applied as RO/NS scavengers. This
      review addresses the most recent progress in the development and application of
      such chemicals and outlines some future perspectives.

PMID- 26219395
TI  - The Interest of Folic Acid in Targeted Photodynamic Therapy.
AB  - Photodynamic therapy is an alternative to chemotherapy and radiotherapy for
      cancer treatment. PDT is clinically applied to treat age-related macular
      degeneration and several types of cancer. Most of the time, the selectivity of
      the treatment is brought about by the application of light. Another strategy to
      improve selectivity is to design and synthesize targeted photosensitizers or
      nanoparticles, which can identify and selectively accumulate within tumor
      tissues. This review presents our inventory of all the data concerning the use of
      folic acid as a promising targeting unit to improve the selectivity of
      photosensitizers to folic acid receptors. We will discuss the strategies that are
      developed to couple folic acid to photosensitizers or nanoparticles as well as
      the influence of the presence of folic acid on the objects' photophysical
      properties and their effects on selectivity and phototoxicity in vitro and in
      vivo. 

PMID- 26219396
TI  - Is self-positive information more appealing than money? Individual differences in
      positivity bias according to depressive symptoms.
AB  - The self-positivity bias, which is inherent to healthy people, is known to be
      blunted in depression. The lack of positive or excessive negative self-reference
      is considered to be a potential mechanism underlying depressive rumination.
      However, the motivational factors that drive people to approach and avoid
      emotional self-related materials are still unclear. Therefore, we measured
      intrinsic motivation that is associated with emotional self-references by using a
      reward-based decision-making task (pay-per-view paradigm). Forty-nine
      undergraduates completed two tasks in which they were asked to choose between
      negative vs. positive references (Task 1) and self vs. other references (Task 2)
      for variable monetary rewards. Participants with lower levels of depressive
      symptoms showed a self-positivity bias, sacrificing rewards for the opportunity
      to engage in positive self-reference, whereas those with higher levels of
      depressive symptoms had no specific preference for either negative or positive
      self-reference (Task 1). However, all participants sacrificed monetary rewards
      for the opportunity for self-reference versus other reference, regardless of the
      symptom level or the primed valence (Task 2). Together, these findings suggest
      that depressive cognition could be characterised by the lack of intrinsic
      motivation for positive self-reference, which is attributable to the biased
      valence selection, but not to self-other preferences.

PMID- 26219397
TI  - Effects of Portulaca oleracea L. Polysaccharides on Phenotypic and Functional
      Maturation of Murine Bone Marrow Derived Dendritic Cells.
AB  - Portulaca oleracea L. is an annual plant widely distributed from the temperate to
      the tropical zones. POL-P3b, a polysaccharide fraction purified from Portulaca
      oleracea L., is able to enhance immunity and inhibit tumor formation. Induction
      of antitumor immunity by dendritic-tumor fusion cells can be modulated by their
      activation status. Mature dendritic cells are significantly better than immature
      dendritic cells at cytotoxic T-lymphocyte induction. In this study, we analyzed
      the effects of POL-P3b on the maturation and function of murine bone-marrow
      derived dendritic cells (DCs) and relevant mechanisms. The phenotypic maturation
      of DCs was confirmed by flow cytometry. We found that POL-P3b upregulated the
      expression of CD80, CD86, CD83, and major histocompatibility complex class II
      molecules on DCs, stimulated production of more interleukin (IL)-12, tumor
      necrosis factor-alpha, and less IL-10. Also, DCs pulsed POL-P3b and freeze-thaw
      antigen increased DCs-driven T cells' proliferation and promoted U14 cells'
      apoptosis. Furthermore, the expression of TLR-4 was significantly increased on
      DCs treated by POL-P3b. These results suggested that POL-P3b may induce DCs
      maturation through TLR-4. Taken together, our results may have important
      implications for the molecular mechanisms of immunopotentiation of POL-P3b, and
      provide direct evidence to suggest that POL-P3b should be considered as a potent
      adjuvant nutrient supplement for DC-based vaccines. 

PMID- 26219398
TI  - TACC3 promotes stemness and is a potential therapeutic target in hepatocellular
      carcinoma.
AB  - Transforming acidic coiled-coil protein 3 (TACC3) is essential for cell mitosis
      and transcriptional functions. In the present study, we first demonstrated that
      both TACC3 protein and mRNA levels were elevated in HCC tissue samples compared
      with non-cancerous tissue biopsies according to western blot analyses,
      immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) assays.
      Moreover, high TACC3 expression was positively correlated with poor overall
      survival (OS) and disease-free survival (DFS) (p < 0.001). Using HCC cell lines,
      we then demonstrated that either TACC3 knockdown or treatment with the potential
      TACC3 inhibitor KHS101 suppressed cell growth and sphere formation as well as the
      expression of stem cell transcription factors, including Bmi1, c-Myc and Nanog.
      Silencing TACC3 may suppress the Wnt/beta-catenin and PI3K/AKT signaling
      pathways, which regulate cancer stem cell-like characteristics. Taken together,
      these data suggest that TACC3 is enriched in HCC and that TACC3 down-regulation
      inhibits the proliferation, clonogenicity, and cancer stem cell-like phenotype of
      HCC cells. KHS101, a TACC3 inhibitor, may serve as a novel therapeutic agent for
      HCC patients with tumors characterized by high TACC3 expression. 

PMID- 26219399
TI  - Functional connectivity for face processing in individuals with body dysmorphic
      disorder and anorexia nervosa.
AB  - BACKGROUND: Body dysmorphic disorder (BDD) and anorexia nervosa (AN) are both
      characterized by distorted perception of appearance. Previous studies in BDD
      suggest abnormalities in visual processing of own and others' faces, but no study
      has examined visual processing of faces in AN, nor directly compared the two
      disorders in this respect. METHOD: We collected functional magnetic resonance
      imaging data on 60 individuals of equivalent age and gender in each of three
      groups--20 BDD, 20 weight-restored AN, and 20 healthy controls (HC)--while they
      viewed images of others' faces that contained only high or low spatial frequency
      information (HSF or LSF). We tested hypotheses about functional connectivity
      within specialized sub-networks for HSF and LSF visual processing, using
      psychophysiological interaction analyses. RESULTS: The BDD group demonstrated
      increased functional connectivity compared to HC between left anterior occipital
      face area and right fusiform face area (FFA) for LSF faces, which was associated
      with symptom severity. Both BDD and AN groups had increased connectivity compared
      to HC between FFA and precuneous/posterior cingulate gyrus for LSF faces, and
      decreased connectivity between FFA and insula. In addition, we found that LSF
      connectivity between FFA and posterior cingulate gyrus was significantly
      associated with thoughts about own appearance in AN. CONCLUSIONS: Results suggest
      similar abnormal functional connectivity within higher-order systems for face
      processing in BDD and AN, but distinct abnormal connectivity patterns within
      occipito-temporal visual networks. Findings may have implications for
      understanding relationships between these disorders, and the pathophysiology
      underlying perceptual distortions.

PMID- 26219400
TI  - Genome-wide analysis of enhancer RNA in gene regulation across 12 mouse tissues.
AB  - Enhancers play a crucial role in gene regulation but the participation of
      enhancer transcripts (i.e. enhancer RNA, eRNAs) in regulatory systems remains
      unclear. We provide a computational analysis on eRNAs using genome-wide data
      across 12 mouse tissues. The expression of genes targeted by transcribing
      enhancer is positively correlated with eRNA expression and significantly higher
      than expression of genes targeted by non-transcribing enhancers. This result
      implies eRNA transcription indicates a state of enhancer that further increases
      gene expression. This state of enhancer is tissue-specific, as the same enhancer
      differentially transcribes eRNAs across tissues. Therefore, the presence of eRNAs
      describes a tissue-specific state of enhancer that is generally associated with
      higher expressed target genes, surmising as to whether eRNAs have gene activation
      potential. We further found a large number of eRNAs contain regions in which
      sequences and secondary structures are similar to microRNAs. Interestingly, an
      increasing number of recent studies hypothesize that microRNAs may switch from
      their general repressive role to an activating role when targeting promoter
      sequences. Collectively, our results provide speculation that eRNAs may be
      associated with the selective activation of enhancer target genes. 

PMID- 26219401
TI  - Assessing the global zoo response to the amphibian crisis through 20-year trends
      in captive collections.
AB  - Global amphibian declines are one of the biggest challenges currently facing the
      conservation community, and captive breeding is one way to address this crisis.
      Using information from the International Species Information System zoo network,
      we examined trends in global zoo amphibian holdings across species, zoo region,
      and species geographical region of origin from 1994 to 2014. These trends were
      compared before and after the 2004 Global Amphibian Assessment to assess whether
      any changes occurred and whether zoo amphibian conservation effort had increased.
      The numbers of globally threatened species (GTS) and their proportional
      representation in global zoo holdings increased and this rate of increase was
      significantly greater after 2004. North American, European, and Oceanian GTS were
      best represented in zoos globally, and proportions of Oceanian GTS held increased
      the most since 2004. South American and Asian GTS had the lowest proportional
      representation in zoos. At a regional zoo level, European zoos held the lowest
      proportions of GTS, and this proportion did not increase after 2004. Since 1994,
      the number of species held in viable populations has increased, and these species
      are distributed among more institutions. However, as of 2014, zoos held 6.2% of
      globally threatened amphibians, a much smaller figure than for other vertebrate
      groups and one that falls considerably short of the number of species for which
      ex situ management may be desirable. Although the increased effort zoos have put
      into amphibian conservation over the past 20 years is encouraging, more focus is
      needed on ex situ conservation priority species. This includes building expertise
      and capacity in countries that hold them and tracking existing conservation
      efforts if the evidence-based approach to amphibian conservation planning at a
      global level is to be further developed. 

PMID- 26219402
TI  - An Inverse Finite Element u/p-Formulation to Predict the Unloaded State of In
      Vivo Biological Soft Tissues.
AB  - Physically realistic patient-specific biomechanical modelling is of paramount
      importance for many medical applications, where the geometry of tissues or organs
      is usually constructed from in vivo images. However, it is common for such
      biological structures to correspond to a deformed state due to being under
      external loadings. This necessitates the determination of the stress distribution
      of the known deformed state through an inverse analysis approach. To achieve
      this, we propose here a generalised finite element displacement/pressure (u/p)
      formulation for evaluating the unloaded configuration of in vivo biological soft
      tissues that exhibit quasi-incompressible behaviour under finite deformations.
      Validity and applicability of the proposed numerical framework to practical
      inverse analysis problems in biomechanics is demonstrated through various
      numerical examples. The corresponding simulations utilise in vivo measurements of
      patient-specific geometries derived from different medical imaging modalities,
      and include recovery of the pressure-free configuration of human aortas and the
      gravity-free shape of the female breast. 

PMID- 26219403
TI  - Effects of Osmolarity on the Spontaneous Calcium Signaling of In Situ Juvenile
      and Adult Articular Chondrocytes.
AB  - Calcium is a universal second messenger that mediates the metabolic activity of
      chondrocytes in articular cartilage. Spontaneous intracellular calcium
      ([Ca(2+)]i) oscillations, similar to those in neurons and myocytes, have recently
      been observed in chondrocytes. This study analyzed and compared the effects of
      different osmotic environments (hypertonic, hypotonic, and isotonic) on the
      spontaneous [Ca(2+)]i signaling of in situ chondrocytes residing in juvenile and
      adult cartilage explants. In spite of a lower cell density, a significantly
      higher percentage of chondrocytes in adult cartilage under all osmotic
      environments demonstrated spontaneous [Ca(2+)]i oscillations than chondrocytes in
      juvenile cartilage. For both juvenile and adult chondrocytes, hypotonic stress
      increased while hypertonic stress decreased the response rates. Furthermore, the
      spatiotemporal characteristics of the [Ca(2+)]i peaks vary in an age-dependent
      manner. In the hypotonic environment, the [Ca(2+)]i oscillation frequency of
      responsive adult cells is almost tripled whereas the juvenile cells respond with
      an increased duration and magnitude of each [Ca(2+)]i peak. Both juvenile and
      adult chondrocytes demonstrated significantly slower [Ca(2+)]i oscillations with
      longer rising and recovery time under the hypertonic condition. Taken together,
      these results shed new insights into the interplay between age and osmotic
      environment that may regulate the fundamental metabolism of chondrocytes.

PMID- 26219404
TI  - Motile Human Neutrophils Sense Ligand Density Over Their Entire Contact Area.
AB  - Neutrophils are key components of the immune system and motility is central their
      function during the inflammatory response. We have previously demonstrated that
      neutrophils are capable of switching their motile phenotype between amoeboid-like
      and keratocyte-like in response to the ligand density of adhesion molecules
      (Henry et al. in Int Biol 6:348-356, 2014). In this study, we engineered planar
      micropatterned surfaces that presented adhesion molecules in local islands of
      high density, separated by regions largely devoid of ligands. By controlling the
      geometry of islands we made arrays in which the local (on island) adhesion
      density was high but the global (multi-island) adhesion density over the entire
      cell-substrate interface was low. Neutrophils in contact with these island arrays
      assumed a well-spread and directionally-persistent motile phenotype (keratocyte
      like) in contrast to the classical amoeboid morphology they display on uniform
      fields of high adhesion density. By virtue of our rationally designed substrates,
      we were able to conclude that neutrophils were integrating the stimulation
      received across their entire contact interface; furthermore, they were able to
      mount this whole cell response on the timescale of seconds. This work
      demonstrates the capacity of adhesive microenvironments to direct the phenotype
      of cell motility, which has broader implications in physiologic processes such as
      inflammation and cancer metastasis.

PMID- 26219405
TI  - Maternal circulating levels of some metabolic syndrome biomarkers in gestational
      diabetes mellitus.
AB  - The aims of the present study were to explore serum levels of lipid profile,
      atherogenic indexes LDL-C/HDL-C, TG/HDL-C, and TC/HDL-C, bilirubin, adiponectin,
      pseudocholinesterase, activities of gamma-glutamyltransferase (GGT), adenosine
      deaminase (ADA), and alpha-amylase, insulin resistance using homeostasis model
      assessment of insulin resistance (HOMA-IR) formula, and assessment of
      correlations between them in gestational diabetes mellitus (GDM) compared with
      normal pregnancy. A cross-sectional study was designed. The patients consisted of
      30 women with GDM. The normal group consisted of 30 healthy pregnant women. The
      Mann-Whitney U test and Spearman's correlation analysis were used for statistical
      analysis. A p value less than 0.05 was considered significant. Serum activities
      of enzymes GGT (p = 0.001) and ADA (p = 0.02) were significantly higher in GDM
      compared with normal pregnancy, while pseudocholinesterase were significantly
      decreased (p = 0.02). However, activity of enzyme alpha-amylase did not show
      significant difference between two groups (p = 0.75). Serum levels of both HDL-C
      and adiponectin were significantly decreased in GDM group (p = 0.001). The
      atherogenic indexes and the HOMA-IR index were significantly higher in GDM (p =
      0.001). Serum activity of ADA showed positive correlation with total cholesterol
      (TC) (r = 0.46, p = 0.01) and CRP (r = 0.66, p = 0.001) in GDM group. Serum
      levels of total bilirubin correlated negatively with both ADA (r = -0.38, p =
      0.04) and triglyceride (r = -0.45, p = 0.01) in women with GDM. Serum activity of
      GGT correlated positively with LDL-C (r = 0.48, p = 0.01) and TC (r = 0.52, p =
      0.003) in GDM group. Increased atherogenic indexes, ADA, GGT, and decreased
      pseudocholinesterase might be risk factors for GDM.

PMID- 26219406
TI  - The heat shock protein 90 inhibitor SNX5422 has a synergistic activity with
      histone deacetylase inhibitors in induction of death of anaplastic thyroid
      carcinoma cells.
AB  - The influence of the heat shock protein 90 (hsp90) inhibitor SNX5422 alone or in
      combination with the histone deacetylase (HDAC) inhibitors PXD101,
      suberoylanilide hydroxamic acid (SAHA), and trichostatin A (TSA) on survival of
      anaplastic thyroid carcinoma (ATC) cells was investigated. In 8505C and CAL62
      cells, SNX5422 caused cell death with concomitant changes in the expression of
      hsp90 client proteins. After treatment of both SNX5422 and PXD101, SAHA and TSA,
      compared with treatment of SNX5422 alone, cell viability was diminished, whereas
      inhibition rate and cytotoxic activity were enhanced. All of the combination
      index values were lower than 1.0, suggesting the synergism between SNX5422 and
      PXD101, SAHA and TSA in induction of cell death. In cells treated with both
      SNX5422 and PXD101, SAHA and TSA, compared with cells treated with SNX5422 alone,
      the protein levels of Akt, phospho-4EBP1, phospho-S6 K, and survivin were
      diminished, while those of gammaH2AX, acetyl. histone H3, acetyl. histone H4,
      cleaved PARP, and cleaved caspase-3 were enhanced. In conclusion, these results
      demonstrate that SNX5422 has a cytotoxic activity in conjunction with alterations
      in the expression of hsp90 client proteins in ATC cells. Moreover, SNX5422
      synergizes with HDAC inhibitors in induction of cytotoxicity accompanied by the
      suppression of PI3K/Akt/mTOR signaling and survivin, and the overexpression of
      DNA damage-related proteins in ATC cells.

PMID- 26219408
TI  - Endoscopy as a diagnostic and therapeutic alternative technique of taeniasis.
AB  - Despite a low incidence in developed countries, gastrointestinal taeniasis should
      be suspected in patients with abdominal pain, diarrhea, anemia, and/or
      malabsorption of unknown origin, even more so if they come from endemic regions
      or areas with poor hygienic and alimentary habits. Diagnosis is traditionally
      reached by identifying the parasite in stools, but more recently both serological
      and immunological approaches are also available. Based on a patient diagnosed by
      gastroscopy, a literature review was undertaken of patients diagnosed by
      endoscopy. We discuss endoscopy as diagnostic modality, and the effectiveness and
      safety that endoscopic treatment may provide in view of the potential risk for
      neurocysticercosis. 

PMID- 26219407
TI  - Lymphocytic infundibulo-neurohypophysitis: a clinical overview.
AB  - Lymphocytic infundibulo-neurohypophysitis is an uncommon inflammatory disorder
      postulated to be autoimmune in origin. Because of the location of inflammation,
      it selectively affects the posterior lobe of the pituitary (neurohypophysis) and
      pituitary stalk (infundibulum). The most common presentation is central diabetes
      insipidus. Although the definitive diagnosis is established histologically by a
      pituitary biopsy, radiological imaging can be valuable in diagnosing this
      condition. In this paper, we provide an overview of the pathophysiology,
      investigations, management, and outcomes of lymphocytic infundibulo
      neurohypophysitis. 

PMID- 26219409
TI  - Identification of Estrogen Response Element in Aquaporin-3 Gene that Mediates
      Estrogen-induced Cell Migration and Invasion in Estrogen Receptor-positive Breast
      Cancer.
AB  - Accumulating evidence suggests that aquaporins (AQPs) may facilitate tumor
      development. The molecular pathways connecting the pathological functions of AQPs
      are unclear and need to be better defined. This study aimed to investigate
      whether AQP3, one of the AQPs expressed highly in breast cancer, had any clinical
      implication in estrogen-receptor (ER) positive breast cancer, and explore the
      regulatory mechanisms of AQP3 in estrogen-related breast cancer progression. Here
      we show that AQP3 is an important enforcer of migration and invasion in breast
      cancer. We, for the first time, reported that ER-positive breast cancer tissues
      obtained from premenopausal patients had higher AQP3 expression when compared to
      those obtained from postmenopausal patients. Estrogen directly upregulates AQP3
      by activating ERE in the promoter of the AQP3 gene. The upregulation of AQP3 can
      influence the expression of molecules related to epithelial-mesenchymal
      transition and the reorganization of actin-cytoskeleton, resulting in enhancement
      of cell migration and invasion in ER-positive breast cancer cells. 

PMID- 26219410
TI  - Preoperative iodine-123 meta-iodobenzylguanidine imaging is a novel predictor of
      left ventricular reverse remodeling during treatment with a left ventricular
      assist device.
AB  - Although left ventricular reverse remodeling (LVRR) is accompanied with an
      improved clinical course during LV assist device (LVAD) treatment, its
      preoperative prediction remains uncertain. Twenty-seven heart failure patients
      with dilated cardiomyopathy were enrolled in this study. Patients underwent
      (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy before LVAD implantation, and
      were monitored at our institute from 2010 to 2014. This study investigated the
      prognostic value of preoperative (123)I-MIBG parameters for predicting
      postoperative LVRR. Of the preoperative variables studied, including (123)I-MIBG
      data, washout rate (WR) <= 39 % was the only significant, independent predictor
      of LVRR (defined as LV ejection fraction >=35 % at 6 months post-LVAD implant
      using univariate and multivariate logistic regression analyses) (p = 0.036, odds
      ratio [OR]:14.45). Improved exercise capacity and more frequent opening of the
      native aortic valve, as well as lower B-type natriuretic peptide plasma levels,
      were observed in LVRR patients (p < 0.05 for all), although beta-blocker doses
      were comparable with those of non-LVRR patients throughout the 6-month LVAD
      support period. In conclusion, preoperative (123)I-MIBG is a novel predictive
      tool of LVRR during LVAD support.

PMID- 26219411
TI  - GABA signalling modulates plant growth by directly regulating the activity of
      plant-specific anion transporters.
AB  - The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in
      plant tissues in response to biotic and abiotic stress, and regulates plant
      growth. Until now it was not known whether GABA exerts its effects in plants
      through the regulation of carbon metabolism or via an unidentified signalling
      pathway. Here, we demonstrate that anion flux through plant aluminium-activated
      malate transporter (ALMT) proteins is activated by anions and negatively
      regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT
      proteins abolishes GABA efficacy but does not alter other transport properties.
      GABA modulation of ALMT activity results in altered root growth and altered root
      tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts
      its multiple physiological effects in plants via ALMT, including the regulation
      of pollen tube and root growth, and that GABA can finally be considered a
      legitimate signalling molecule in both the plant and animal kingdoms. 

PMID- 26219412
TI  - Heat-induced conformational changes of TET peptidase from crenarchaeon
      Desulfurococcus kamchatkensis.
AB  - The effects of heating on the structure and stability of multimeric TET
      aminopeptidase (APDkam589) were studied by differential scanning calorimetry,
      tryptophan fluorescence quenching, and dynamic light scattering. Thermally
      induced structural changes in APDkam589 were found to occur in two phases: local
      conformational changes, which occur below 70  degrees C and are not associated
      with thermal denaturation of the protein, and global structural changes (above 70
      degrees C) induced by irreversible thermal unfolding of the protein accompanied
      by its spontaneous aggregation. These results may explain the bell-shaped
      temperature dependence with a maximum at ~70  degrees C previously observed for
      enzymatic activity of APDkam589. Interestingly, the thermal unfolding of
      APDkam589 at about 81.2  degrees C is accompanied by a so-called blue-shift of
      about 10 nm-a shift of the Trp fluorescence spectrum toward shorter wavelength.
      From this point of view, APDkam589 is quite different from most proteins, which
      are characterized by a long wavelength shift of the spectrum ("red-shift") upon
      denaturation. The blue-shift of the Trp fluorescence spectrum reflects the
      changes in the environment of Trp residues, which becomes more hydrophobic upon
      denaturation. The molecular structure of APDkam589 was determined by X-ray
      diffraction. The monomer of APDkam589 has six Trp residues, five of which are on
      the external surface of the dodecamer. Therefore, the blue-shift of the Trp
      fluorescence spectrum can be explained, at least partly, by aggregation of
      APDkam589, which occurs simultaneously with its thermal denaturation and probably
      makes the environment of these Trp residues more hydrophobic.

PMID- 26219413
TI  - Nephronophthisis: should we target cysts or fibrosis?
AB  - Ciliopathy nephronophthisis (NPHP), a common cause of end-stage renal disease
      (ESRD) in children and young adults, is characterized by disintegration of the
      tubular basement membrane accompanied by irregular thickening and attenuation,
      interstitial fibrosis and tubular atrophy, and occasionally cortico-medullary
      cyst formation. Pharmacological approaches that delay the development of ESRD
      could potentially extend the window of therapeutic opportunity for this group of
      patients, generating time to find an appropriate donor or even for new treatments
      to mature. In this review we provide an overview of compounds that have been
      tested to ameliorate kidney cysts and/or fibrosis. We also revisit paclitaxel as
      a potential strategy to target fibrosis in NPHP. At low dosage this chemotherapy
      drug shows promising results in rodent models of renal fibrosis. Possible adverse
      events and safety of paclitaxel treatment in pediatric patients would need to be
      investigated, as would the efficacy, optimum dose, and administration schedule
      for the treatment of renal fibrosis in NPHP patients. Paclitaxel is an approved
      drug for human use with known pharmacokinetics, which could potentially be used
      in other ciliopathies through targeting the microtubule skeleton. 

PMID- 26219414
TI  - Dietary DHA reduces downstream endocannabinoid and inflammatory gene expression
      and epididymal fat mass while improving aspects of glucose use in muscle in
      C57BL/6J mice.
AB  - OBJECTIVES: Endocannabinoid system (ECS) overactivation is associated with
      increased adiposity and likely contributes to type 2 diabetes risk. Elevated
      tissue cannabinoid receptor 1 (CB1) and circulating endocannabinoids (ECs)
      derived from the n-6 polyunsaturated acid (PUFA) arachidonic acid (AA) occur in
      obese and diabetic patients. Here we investigate whether the n-3 PUFA
      docosahexaenoic acid (DHA) in the diet can reduce ECS overactivation (that is,
      action of ligands, receptors and enzymes of EC synthesis and degradation) to
      influence glycemic control. This study targets the ECS tonal regulation of
      circulating glucose uptake by skeletal muscle as its primary end point. DESIGN:
      Male C57BL/6J mice were fed a semipurified diet containing DHA or the control
      lipid. Serum, skeletal muscle, epididymal fat pads and liver were collected after
      62 and 118 days of feeding. Metabolites, genes and gene products associated with
      the ECS, glucose uptake and metabolism and inflammatory status were measured.
      RESULTS: Dietary DHA enrichment reduced epididymal fat pad mass and increased ECS
      related genes, whereas it reduced downstream ECS activation markers, indicating
      that ECS activation was diminished. The mRNA of glucose-related genes and
      proteins elevated in mice fed the DHA diet with increases in DHA-derived and
      reductions in AA-derived EC and EC-like compounds. In addition, DHA feeding
      reduced plasma levels of various inflammatory cytokines, 5-lipoxygenase-dependent
      inflammatory mediators and the vasoconstrictive 20-HETE. CONCLUSIONS: This study
      provides evidence that DHA feeding altered ECS gene expression to reduce CB1
      activation and reduce fat accretion. Furthermore, the DHA diet led to higher
      expression of genes associated with glucose use by muscle in mice, and reduced
      those associated with systemic inflammatory status.

PMID- 26219415
TI  - Transient hypoxia reprograms differentiating adipocytes for enhanced insulin
      sensitivity and triglyceride accumulation.
AB  - OBJECTIVES: To investigate the impact of transient (2-4 h) hypoxia on metabolic
      reprogramming of adipocytes. METHODS: The impact of transient hypoxia on
      metabolic reprogramming was investigated in 3T3-L1 cells before and after
      differentiation. Glucose uptake, fatty acid oxidation, lipolysis and mitochondria
      were examined to determine the hypoxia effects. Preadipocytes were exposed to
      transient hypoxia (4 h day(-1)) in the course of differentiation. Insulin
      sensitivity and triglyceride (TG) accumulation was examined in the cells at the
      end of differentiation to determine the reprogramming effects. AMP-activated
      protein kinase (AMPK) activity and gene expression were determined by
      quantitative reverse transcriptase-PCR and western blotting in search for
      mechanism of the reprogramming. RESULTS: In acute response to hypoxia, adipocytes
      exhibited an increase in insulin-dependent and -independent glucose uptake. Fatty
      acid beta-oxidation and pyruvate dehydrogenase activity were decreased. Multiple
      exposures of differentiating adipocytes to transient hypoxia enhanced insulin
      signaling, TG accumulation and expression of antioxidant genes in differentiated
      adipocytes in the absence of hypoxia. The metabolic memory was associated with
      elevated AMPK activity and gene expression (GLUT1, PGC-1alpha, PPARgamma, SREBP,
      NRF-1, ESRRalpha, LPL). The enhanced insulin sensitivity was blocked by an AMPK
      inhibitor. CONCLUSIONS: Repeated exposure of differentiating adipocytes to
      transient hypoxia is able to reprogram the cells for increased TG accumulation
      and enhanced insulin sensitivity. The metabolic alterations were observed in
      postdifferentiated cells under normoxia. The reprogramming involves AMPK
      activation and gene expression in the metabolic pathways in cytosol and
      mitochondria.

PMID- 26219416
TI  - Is the timing of caloric intake associated with variation in diet-induced
      thermogenesis and in the metabolic pattern? A randomized cross-over study.
AB  - BACKGROUND/OBJECTIVES: Food-induced thermogenesis is generally reported to be
      higher in the morning, although contrasting results exist because of differences
      in experimental settings related to the preceding fasting, exercise, sleeping and
      dieting. To definitively answer to this issue, we compared the calorimetric and
      metabolic responses to identical meals consumed at 0800 hours and at 2000 hours
      by healthy volunteers, after standardized diet, physical activity, duration of
      fast and resting. SUBJECTS/METHODS: Twenty subjects (age range 20-35 years, body
      mass index=19-26 kg m(-)(2)) were enrolled to a randomized cross-over trial. They
      randomly received the same standard meal in the morning and, 7 days after, in the
      evening, or vice versa. A 30-min basal calorimetry was performed; a further 60
      min calorimetry was done 120-min after the beginning of the meal. Blood samples
      were drawn every 30-min for 180-min. General linear models, adjusted for period
      and carry-over, were used to evaluate the 'morning effect', that is, the
      difference of morning delta (after-meal minus fasting values) minus evening delta
      (after-meal minus fasting values) of the variables. RESULTS: Fasting resting
      metabolic rate (RMR) did not change from morning to evening; after-meal RMR
      values were significantly higher after the morning meal (1916; 95% confidence
      interval (CI)=1792, 2041 vs 1756; 1648, 1863 kcal; P<0.001). RMR was
      significantly increased after the morning meal (90.5; 95% CI=40.4, 140.6 kcal;
      P<0.001), whereas differences in areas-under-the-curve for glucose (-1800; -2564,
      1036 mg dl(-1) * h, P<0.001), log-insulin (-0.19; -0.30,-0.07 MUU ml(-1) * h;
      P=0.001) and fatty free acid concentrations (-16.1;-30.0,-2.09 mmol l(-1) * h;
      P=0.024) were significantly lower. Delayed and larger increases in glucose and
      insulin concentrations were found after the evening meals. CONCLUSIONS: The same
      meal consumed in the evening determined a lower RMR, and increased
      glycemic/insulinemic responses, suggesting circadian variations in the energy
      expenditure and metabolic pattern of healthy individuals. The timing of meals
      should probably be considered when nutritional recommendations are given.

PMID- 26219417
TI  - Effects of long-term treatment with testosterone on weight and waist size in 411
      hypogonadal men with obesity classes I-III: observational data from two registry
      studies.
AB  - BACKGROUND/OBJECTIVES: Long-term testosterone replacement therapy (TRT) up to 5
      years has been shown to produce progressive and sustainable weight loss (WL) in
      hypogonadal men. This study investigated effects of long-term TRT up to 8 years
      in hypogonadal men with different obesity classes. SUBJECTS/METHODS: From two
      independent observational registries we identified a total of 411 obese,
      hypogonadal men receiving TRT in urological clinics. The effects of TRT on
      anthropometric as well as metabolic parameters were studied for a maximum
      duration of 8 years, mean follow-up: 6 years. All men received long-acting
      injections of testosterone undecanoate in 3-monthly intervals. RESULTS: In all
      three classes of obesity, T therapy produced significant WL, decrease in waist
      circumference (WC) and body mass index (BMI). In patients with class I obesity,
      mean weight decreased from 102.6+/-6.4 to 84.1+/-4.9 kg, change from baseline: 
      17.4+/-0.5 kg and -16.8+/-0.4%. WC in this group of patients decreased from
      106.8+/-7.4 to 95.1+/-5.3 cm, change from baseline: -10.6+/-0.3 cm. BMI decreased
      from 32.69+/-1.4 to 27.07+/-1.57, change from baseline: -5.52+/-0.15 kg m(-2). In
      patients with class II obesity, weight decreased from 116.8+/-6.9 to 91.3+/-6.3
      kg, change from baseline: -25.3+/-0.5 kg and -21.5+/-0.4%. WC decreased from
      113.5+/-7.5 to 100.0+/-5.4 cm, change from baseline: -13.9+/-0.4 cm. BMI
      decreased from 37.32+/-1.45 to 29.49+/-1.71, change from baseline: -8.15+/-0.17
      kg m(-2). In patients with class III obesity, weight decreased from 129.0+/-5.6
      to 98.9+/-4.8 kg, change from baseline: -30.5+/-0.7 kg and -23.6+/-0.5%. WC
      decreased from 118.5+/-5.6 to 103.8+/-4.9 cm, change from baseline: -14.3+/-0.4
      cm. BMI decreased from 41.93+/-1.48 to 32.46+/-1.59, change from baseline -9.96+/
      0.29 kg m(-2). CONCLUSIONS: Testosterone therapy appears to be an effective
      approach to achieve sustained WL in obese hypogonadal men irrespective of
      severity of obesity. Based on these findings we suggest that T therapy offers
      safe and effective treatment strategy of obesity in hypogonadal men.

PMID- 26219418
TI  - Induction of p53-independent apoptosis by ectopic expression of HOXA5 in human
      liposarcomas.
AB  - Dedifferentiated liposarcoma (DDLPS) is a highly malignant subtype of human
      liposarcoma (LPS), whose genomic profile is characterized by chromosomal
      amplification at 12q13-q22. miR-26a-2 is one of the most frequently amplified
      genes in the region, and inhibition of its downstream target genes likely
      contributes to LPS tumorigenesis. Our previous study of LPS predicted homeobox
      protein A5 (HOXA5) as a target of miR-26a-2, and here we explored further the
      function of HOXA5, and its relationship with miR-26a-2 in DDLPS cells. Compared
      to normal human adipocytes, all LPS cell lines showed significant downregulation
      of HOXA5 (p = 0.046), and inhibition of miR-26a-2 using anti-miR-26a-2
      substantially upregulated HOXA5 expression in these LPS cells. Interestingly,
      overexpression of HOXA5 alone induced very strong apoptotic response of LPS
      cells. HOXA5-induced apoptosis was p53-independent and caspase-dependent.
      Surprisingly, overexpression of HOXA5 induced nuclear translocation of RELA
      (p65), which was not associated with the transcriptional activity of RELA.
      Rather, nucleolar sequestration of RELA was observed. Overall, our study
      demonstrated for the first time that the downregulation of HOXA5 in LPS cells,
      partly by overexpression of miR-26a-2 in DDLPS, confers LPS cells resistance to
      apoptotic death. Further studies are required to understand the relationship of
      HOXA5 and the NFkappaB pathway in LPS cells. 

PMID- 26219419
TI  - "On the Sidelines": Access to Autism-Related Services in the West Bank.
AB  - We examined access to autism-related services among Palestinians (N = 24) raising
      children with autism spectrum disorder (ASD) in the West Bank. Using qualitative
      methods, we identified five primary interview themes. Poor screening, diagnostic,
      and psychoeducational practices were prevalent, as parents reported service
      providers minimized parental concerns and communicated ineffectively with the
      caregivers regarding treatment options. Geographic barriers and financial burdens
      prevented many families from seeking or maintaining services. Limited service
      availability was a dominant barrier: parents reported limited or denied access to
      education, community-based services, and ASD-specific interventions.
      Consequently, several families noted their children did not receive any services
      whatsoever. Research, practices and policies to address the shortage of services
      for children with ASD are urgently needed in the West Bank.

PMID- 26219420
TI  - Activation-induced cytidine deaminase in B cells of hepatits C virus-related
      cryoglobulinaemic vasculitis.
AB  - Immunoglobulin variable region heavy chain (IgVH ) somatic gene diversification
      is instrumental in the transformation process that characterizes hepatitis C
      virus (HCV)-related B cell lymphoproliferative disorders. However, the extent to
      which activation-induced cytidine deaminase (AID), an enzyme essential for IgV
      gene somatic hypermutation (SHM), is active in cryoglobulinaemic vasculitis (CV)
      remains unclear. AID mRNA expression in the peripheral blood of 102 chronically
      hepatitis C virus (HCV)-infected patients (58 with and 44 without CV) and 26
      healthy subjects was investigated using real-time reverse transcription
      polymerase chain reaction (RT-PCR). The features of activation-induced cytidine
      deaminase (AID) protein and mRNA transcripts were explored in liver tissue
      biopsies and portal tracts isolated using laser capture microdissection. In
      chronically HCV-infected patients, AID mRNA expression was almost threefold
      higher in those with than in those without CV and sevenfold higher than in
      healthy subjects (median-fold: 6.68 versus 2.54, P = 0.03 and versus 0.95, P =
      0.0003). AID transcript levels were significantly higher in polyclonal than in
      clonally restricted B cell preparations in either CV or non-CV patients (median
      fold, 15.0 versus 2.70, P = 0.009 and 3.46 versus 1.58, P = 0.02, respectively).
      AID gene expression was found to be related negatively to age and virological
      parameters. AID protein was found in portal tracts containing inflammatory cells
      that, in several instances, expressed AID mRNA transcripts. Our data indicate
      that the aberrant expression of AID may reflect continuous B cell activation and
      sustained survival signals in HCV-related CV patients.

PMID- 26219421
TI  - Is Aortic Valve Leaflet Morphology Predictive of Outcome in Pediatric Aortic
      Valve Stenosis?
AB  - BACKGROUND: Initial palliative treatment of congenital aortic valve stenosis
      consists of either surgical commissurotomy or transcatheter balloon
      valvuloplasty. The basis for selection of primary approach usually is ill
      defined. It was hypothesized that aortic valve characteristics may be helpful in
      directing choice of intervention. This study assesses the impact of valve
      morphology on time to reintervention after catheter- or surgical-based therapy.
      METHODS: A retrospective review of preprocedural echocardiographic aortic outflow
      characteristics was compared with outcomes of primary surgical or balloon valve
      interventions. Characteristics studied included (1) annular dimension; (2)
      leaflet number; (3) leaflet excursion; and (4) degree of leaflet coaptation.
      Patients included those <20 years with a primary diagnosis of aortic stenosis
      (AS) and no other hemodynamically significant lesions at our institutions from
      2000 to 2011. A total of 102 patients were included, 31 classified as having
      critical and 71 as having noncritical aortic stenosis. Of the patients, 79 were
      male, and 50 underwent primary catheter intervention. Echo parameters were
      compared with procedural outcome as defined by death or need for reintervention.
      Receiver operator curves were utilized to determine the point within each
      morphologic feature where the greatest difference occurred. This was utilized as
      the distinguishing point within each the morphologic group. Analysis was
      conducted separately for critical and noncritical aortic stenosis. RESULTS:
      Kaplan-Meier analysis demonstrated no significant difference in time to
      reintervention or death whether initial palliation consisted of surgical
      commissurotomy or balloon valvuloplasty with respect to any of the morphologic
      characteristics studied. CONCLUSION: Patients with AS do equally well with
      surgical commissurotomy or balloon valvuloplasty as initial palliation. This
      holds true for those with either critical or noncritical aortic stenosis. Valve
      morphology did not help in selection of initial palliative strategy. Current
      technologies should enable an improved selection of initial palliative approach
      through thoughtful, randomized trials.

PMID- 26219422
TI  - Expanding our understanding of behavioural difficulties associated with autism
      spectrum disorder.

PMID- 26219423
TI  - Australian oral health case notes: assessment of forensic relevance and adherence
      to recording guidelines.
AB  - BACKGROUND: Dental case notes record clinical diagnoses and treatments, as well
      as providing continuity of patient care. They are also used for dento-legal
      litigation and forensic purposes. Maintaining accurate and comprehensive dental
      patient records is a dental worker's ethical and legal obligation. METHODS:
      Australian registered specialist forensic odontologists were surveyed to
      determine the relevance of recorded case note items for dental identification. A
      dental case notes sample was assessed for adherence with odontologist nominated
      forensic value and compiled professional record keeping guidelines of forensic
      relevance. Frequency of item recording, confidence interval, examiner agreement
      and statistical significance were determined. RESULTS: Broad agreement existed
      between forensic odontologists as to which recorded dental items have most
      forensic relevance. Inclusion frequency of these items in sampled case notes
      varied widely (e.g. single area radiographic view present in 75%, CI = 65.65
      82.50; completed odontogram in 56%, CI = 46.23-65.33). Recording of information
      specified by professional record keeping guidelines also varied, although overall
      inclusion was higher than for forensically desired items (e.g. patient's full
      name in 99%, CI = 94.01 - >99.99; named treating practitioner in 23%, CI = 15.78
      32.31). CONCLUSIONS: Many sampled dental case notes lacked details identified as
      being valuable by forensic specialists and as specified by professional record
      keeping guidelines.

PMID- 26219424
TI  - Initial experience of reduced port surgery using a two-surgeon technique for
      colorectal cancer.
AB  - BACKGROUND: With the decreasing number of surgeons on surgical teams, reduced
      port surgery (RPS) operations have become popular. We herein present our initial
      experience with RPS, which was successfully performed using a two-surgeon
      technique. A retrospective analysis was performed to compare the two-surgeon
      technique with conventional laparoscopic colectomy and evaluate its efficacy.
      METHODS: A total of 535 patients were eligible among 749 registered patients.
      Conventional multiport laparoscopic colectomy with three surgeons and RPS using
      the two-surgeon technique with a surgeon and surgeon's assistant were performed
      in 429 and 106 cases, respectively. The patient characteristics, short-term
      outcomes (including intraoperative and postoperative findings) and pathological
      results were recorded and analyzed. RESULTS: The two groups were similar with
      respect to age, gender, BMI, history of abdominal surgery, depth of tumor
      invasion and TNM classification. Reconstruction via extracorporeal functional end
      to-end anastomosis was performed in a significantly higher number of patients in
      the two-surgeon technique group (74 %) than in the conventional laparoscopic
      colectomy group (57 %). Furthermore, the mean operative time in the two-surgeon
      technique group (117.9 min) was significantly shorter than that observed in the
      conventional laparoscopic colectomy group (170 min), and the median postoperative
      hospital stay was significantly shorter in the two-surgeon technique group (6
      days) than in the conventional laparoscopic colectomy group (7 days). There were
      no major postoperative complications. The final TNM stage was similar in both
      procedures. CONCLUSION: RPS using the two-surgeon technique compares favorably
      with conventional laparoscopic colectomy and is considered to be a safe and
      successful procedure.

PMID- 26219425
TI  - Laser generated gold nanocorals with broadband plasmon absorption for
      photothermal applications.
AB  - Gold nanoparticles with efficient plasmon absorption in the visible and near
      infrared (NIR) regions, biocompatibility and easy surface functionalization are
      of interest for photothermal applications. Herein we describe the synthesis and
      photothermal properties of gold "nanocorals" (AuNC) obtained by laser irradiation
      of Au nanospheres (AuNS) dispersed in liquid solution. AuNC are formed in two
      stages: by photofragmentation of AuNS, followed by spontaneous unidirectional
      assembly of gold nanocrystals. The whole procedure is performed without chemicals
      or templating compounds, hence the AuNC can be coated with thiolated molecules in
      one step. We show that AuNC coated with thiolated polymers are easily dispersed
      in an aqueous environment or in organic solvents and can be included in polymeric
      matrixes to yield a plasmonic nanocomposite. AuNC dispersions exhibit flat
      broadband plasmon absorption ranging from the visible to the NIR and unitary
      light-to-heat conversion. Besides, in vitro biocompatibility experiments assessed
      the absence of cytotoxic effects even at a dose as high as 100 MUg mL(-1). These
      safe-by-designed AuNC are promising for use in various applications such as
      photothermal cancer therapy, light-triggered drug release, antimicrobial
      substrates, optical tomography, obscurant materials and optical coatings. 

PMID- 26219426
TI  - EFFECTS OF RELIGIOUS VERSUS STANDARD COGNITIVE-BEHAVIORAL THERAPY ON OPTIMISM IN
      PERSONS WITH MAJOR DEPRESSION AND CHRONIC MEDICAL ILLNESS.
AB  - BACKGROUND: We compared the effectiveness of religiously integrated cognitive
      behavioral therapy (RCBT) versus standard CBT (SCBT) on increasing optimism in
      persons with major depressive disorder (MDD) and chronic medical illness.
      METHODS: Participants aged 18-85 were randomized to either RCBT (n = 65) or SCBT
      (n = 67) to receive ten 50-min sessions remotely (94% by telephone) over 12
      weeks. Optimism was assessed at baseline, 12 and 24 weeks by the Life Orientation
      Test-Revised. Religiosity was assessed at baseline using a 29-item scale composed
      of religious importance, individual religious practices, intrinsic religiosity,
      and daily spiritual experiences. Mixed effects growth curve models were used to
      compare the effects of treatment group on trajectory of change in optimism.
      RESULTS: In the intention-to-treat analysis, both RCBT and SCBT increased
      optimism over time, although there was no significant difference between
      treatment groups (B = -0.75, SE = 0.57, t = -1.33, P = .185). Analyses in the
      highly religious and in the per protocol analysis indicated similar results.
      Higher baseline religiosity predicted an increase in optimism over time (B =
      0.07, SE = 0.02, t = 4.12, P < .0001), and higher baseline optimism predicted a
      faster decline in depressive symptoms over time (B = -0.61, SE = 0.10, t = -6.30,
      P < .0001), both independent of treatment group. CONCLUSIONS: RCBT and SCBT are
      equally effective in increasing optimism in persons with MDD and chronic medical
      illness. While baseline religiosity does not moderate this effect, religiosity
      predicts increases in optimism over time independent of treatment group.

PMID- 26219427
TI  - Sequential injection analysis with chemiluminescence detection for rapid
      monitoring of commercial Calendula officinalis extractions.
AB  - INTRODUCTION: Plant extracts containing high levels of antioxidants are desirable
      due to their reported health benefits. Most techniques capable of determining the
      antioxidant activity of plant extracts are unsuitable for rapid at-line analysis
      as they require extensive sample preparation and/or long analysis times.
      Therefore, analytical techniques capable of real-time or pseudo real-time at-line
      monitoring of plant extractions, and determination of extraction endpoints, would
      be useful to manufacturers of antioxidant-rich plant extracts. OBJECTIVES: To
      develop a reliable method for the rapid at-line extraction monitoring of
      antioxidants in plant extracts. MATERIALS AND METHODS: Calendula officinalis
      extracts were prepared from dried flowers and analysed for antioxidant activity
      using sequential injection analysis (SIA) with chemiluminescence (CL) detection.
      The intensity of CL emission from the reaction of acidic potassium permanganate
      with antioxidants within the extract was used as the analytical signal. The SIA
      CL method was applied to monitor the extraction of C. officinalis over the course
      of a batch extraction to determine the extraction endpoint. Results were compared
      with those from ultra high performance liquid chromatography (UHPLC). RESULTS:
      Pseudo real-time, at-line monitoring showed the level of antioxidants in a batch
      extract of Calendula officinalis plateaued after 100 min of extraction. These
      results correlated well with those of an offline UHPLC study. CONCLUSION: SIA-CL
      was found to be a suitable method for pseudo real-time monitoring of plant
      extractions and determination of extraction endpoints with respect to antioxidant
      concentrations. The method was applied at-line in the manufacturing industry.

PMID- 26219428
TI  - Reply: To PMID 25516154.

PMID- 26219429
TI  - D-Glucosamine as a novel chiral auxiliary for the stereoselective synthesis of P
      stereogenic phosphine oxides.
AB  - D-Glucosamine was successfully employed as a chiral auxiliary for the
      enantioselective synthesis of phosphine oxides. The influence of the anomeric
      position was also investigated and revealed the excellent ability of the alpha
      anomer to perform this transformation in a highly selective fashion. The
      methodology employed consisted of three steps: diastereoselective formation of
      the oxazaphospholidine followed by subsequent selective cleavage of P-N and P-O
      bonds by reaction with two Grignard reagents. P-epimers oxazaphospholidines were
      prepared switching from a P(v) to a P(III) precursor, thus allowing for the
      synthesis of enantiomeric phosphine oxides. In addition, the chiral auxiliary
      could be recovered and efficiently recycled.

PMID- 26219430
TI  - Alcohol dependence and treatment utilization in Europe - a representative cross
      sectional study in primary care.
AB  - BACKGROUND: Alcohol dependence (AD) in Europe is prevalent and causes
      considerable health burden. Recognition by general practitioners (GPs) and
      provision of or referral to treatment may contribute to reduce this burden. This
      paper studied AD prevalence in varying European primary care settings and
      examined who received treatment. METHODS: In a cross-sectional multi-centre study
      in six European countries, 358 general practitioners assessed 13,003 primary care
      patients between January 2013 and January 2014, of which 8,476 patients were
      interviewed, collecting information on socio-demographics, physical and mental
      problems, and on alcohol use, problems and treatment. AD diagnoses were
      determined by GPs' clinical judgement and a standardized interview. A wide
      definition for AD treatment included individual and group interventions provided
      by different health professionals. Descriptive as well as inferential statistics
      were employed. RESULTS: AD was prevalent among patients in European primary
      health care settings (8.7 %, 95 % confidence interval (CI): 8.1-9.3 %). Treatment
      rates were low (22.3 % of all AD cases, 95 % CI: 19.4-25.2 %). For both
      prevalence and treatment utilization, considerable country variations were
      observed. AD was associated with a number of socio-economic disadvantages (e.g.
      higher unemployment rate) and higher physical (e.g., liver disease, hypertension)
      and mental comorbidities (e.g., depression, anxiety). Liver problems, mental
      distress and daily amount of alcohol used were higher among treated versus
      untreated male patients with AD. CONCLUSION: A minority of people identified as
      having AD received treatment, showing heavier drinking patterns and a higher
      level of co-morbidity. Different types of treatment, depending on severity of AD,
      should be considered.

PMID- 26219431
TI  - Structure of Ctk3, a subunit of the RNA polymerase II CTD kinase complex, reveals
      a noncanonical CTD-interacting domain fold.
AB  - CTDK-I is a yeast kinase complex that phosphorylates the C-terminal repeat domain
      (CTD) of RNA polymerase II (Pol II) to promote transcription elongation. CTDK-I
      contains the cyclin-dependent kinase Ctk1 (homologous to human CDK9/CDK12), the
      cyclin Ctk2 (human cyclin K), and the yeast-specific subunit Ctk3, which is
      required for CTDK-I stability and activity. Here we predict that Ctk3 consists of
      a N-terminal CTD-interacting domain (CID) and a C-terminal three-helix bundle
      domain. We determine the X-ray crystal structure of the N-terminal domain of the
      Ctk3 homologue Lsg1 from the fission yeast Schizosaccharomyces pombe at 2.0 A
      resolution. The structure reveals eight helices arranged into a right-handed
      superhelical fold that resembles the CID domain present in transcription
      termination factors Pcf11, Nrd1, and Rtt103. Ctk3 however shows different surface
      properties and no binding to CTD peptides. Together with the known structure of
      Ctk1 and Ctk2 homologues, our results lead to a molecular framework for analyzing
      the structure and function of the CTDK-I complex.

PMID- 26219432
TI  - Characterization of curdlan produced by Agrobacterium sp. IFO 13140 cells
      immobilized in a loofa sponge matrix, and application of this biopolymer in the
      development of functional yogurt.
AB  - BACKGROUND: Agrobacterium sp. IFO 13140 cells were immobilized on a loofa sponge
      and used to produce curdlan over five successive cycles. The interaction between
      microbial cells and the loofa sponge as well as the produced curdlan were
      characterized by Fourier transform infrared-attenuated total reflectance (FTIR
      ATR) spectrometry. The purity of the curdlan was also evaluated. The storage
      stability of the immobilized cells was assessed and the produced curdlan was used
      in a functional yogurt formulation. RESULTS: The average curdlan production by
      immobilized cells was 17.84 g L(-1) . The presence of the microorganism in the
      sponge was confirmed and did not cause alterations in the matrix, and the
      chemical structure of the curdlan was the same as that of commercial curdlan. The
      purity of both was similar. The immobilized cells remained active after 300 days
      of storage at -18  degrees C. The use of the produced curdlan in a functional
      yogurt resulted in a product with lower syneresis. CONCLUSION: A large number of
      cells physically adhered to the surface of loofa sponge fibers, and its use as an
      immobilization matrix to produce curdlan was effective. The use of the produced
      curdlan in yogurt allowed the development of a more stable product. (c) 2015
      Society of Chemical Industry.

PMID- 26219433
TI  - Gold(I)-Catalyzed Tandem Transformation with Diynes: Rapid Access to Linear
      Cyclopentenone-Fused Polycyclic Molecules.
AB  - An efficient and convenient synthesis of useful linear cyclopentenone-fused
      polycyclic compounds has been achieved through a novel gold(I)-catalyzed
      transformation of diynes. The method demonstrates high product yields and
      tolerates of a wide variety of important functional groups. Gold-vinylidene
      formation, methoxy group migration, and Nazarov-type cyclization are proposed to
      be the key steps in the reaction pathway. The synthetic utility of this method is
      demonstrated by converting the product to eight-membered-ring-fused compound. 

PMID- 26219434
TI  - Software for browsing sectioned images of a dog body and generating a 3D model.
AB  - The goals of this study were (1) to provide accessible and instructive browsing
      software for sectioned images and a portable document format (PDF) file that
      includes three-dimensional (3D) models of an entire dog body and (2) to develop
      techniques for segmentation and 3D modeling that would enable an investigator to
      perform these tasks without the aid of a computer engineer. To achieve these
      goals, relatively important or large structures in the sectioned images were
      outlined to generate segmented images. The sectioned and segmented images were
      then packaged into browsing software. In this software, structures in the
      sectioned images are shown in detail and in real color. After 3D models were made
      from the segmented images, the 3D models were exported into a PDF file. In this
      format, the 3D models could be manipulated freely. The browsing software and PDF
      file are available for study by students, for lecture for teachers, and for
      training for clinicians. These files will be helpful for anatomical study by and
      clinical training of veterinary students and clinicians. Furthermore, these
      techniques will be useful for researchers who study two-dimensional images and 3D
      models.

PMID- 26219436
TI  - Stability, equilibrium morphology and hydration of ZrC(111) and (110) surfaces
      with H2O: a combined periodic DFT and atomistic thermodynamic study.
AB  - ZrC is a non-oxide ultra-high temperature ceramic (UHTC) material with excellent
      physical and mechanical properties used in nuclear plants and jet propulsion
      engines. However, the mechanical properties can be lost because of the easy
      oxidation of its grain surfaces. One way of dealing with such a problem is to
      coat the surface with inert carbides like SiC which can be grafted onto the ZrC
      surface by first modifying the exposed surfaces with reactive molecules. The
      stability of different terminations of the (111) facet was studied and the most
      stable is the termination on both surface layers by Zr atoms as it has been
      observed experimentally. A DFT calculation study jointly with atomistic
      thermodynamic modelling has been used to study the reactivity of the (111) and
      (110) facets with H2O. H2O dissociates into surface hydroxyl groups with the
      release of H2 and the OH groups preferentially adsorb at high surface coverage
      (high adsorption energies at 1 ML coverage). The study of adsorption of H2O onto
      other low index surfaces allows the determination of the equilibrium morphology
      of the ZrC nanocrystallites in different environments. In vacuum, ZrC
      nanocrystallites reveal a cubic structure with much of the (100) surface and a
      small amount of the (111) facets at the corners. Hydration of the (111) surface
      was a strong process and hence water can be removed from the surface at
      temperatures above 1200 K and pressures lower than 10(-9) bar while higher
      pressures of H2 in the gas phase enhance the removal of water. The Wulff
      construction of the nanocrystallites after hydration indicates only the (111)
      surface at lower temperatures while revealing the (100) facets at higher
      temperatures. Thus whatever the experimental conditions be, the (110) facet does
      not have to be considered. 

PMID- 26219437
TI  - A comprehensive classification of solvent systems used for natural product
      purifications in countercurrent and centrifugal partition chromatography.
AB  - Using both library paper copies and modern electronic copies, every known,
      published, English-language journal paper that employs either countercurrent or
      centrifugal partition chromatography solvent systems for natural product
      purifications has been studied and the solvent systems classified in a
      comprehensive database. Papers were studied from the earliest found examples
      containing natural product separations in 1984 until the end of 2014. In total,
      2594 solvent systems have been classified, of which 272 are gradient systems. To
      observe any trends or patterns in the data, the natural product solutes were
      divided into 21 classes and the solvent systems into 7 different types. The
      complete database, sorted according to natural product class, is available for
      download to assist separation scientists in future liquid-liquid chromatography
      purifications.

PMID- 26219438
TI  - A comparative study of Ir(III) complexes with pyrazino[2,3-f][1,10]phenanthroline
      and pyrazino[2,3-f][4,7]phenanthroline ligands in light-emitting electrochemical
      cells (LECs).
AB  - We report the comparative study of the electrochemical and photoluminescent
      properties of two Ir(iii) complexes described as [Ir(F2ppy)2(N^N)][PF6], where
      the F2ppy ligand is 2-(2,4-difluorophenyl)pyridine and the N^N ligands are
      pyrazino[2,3-f][1,10]phenanthroline (ppl) and pyrazino[2,3-f][4,7]phenanthroline
      (ppz). The complexes were used for the fabrication of light-emitting
      electrochemical cells (LECs). The structures of the complexes have been
      corroborated by X-ray crystallography. Theoretical calculations were performed to
      understand the photophysical behavior of the complexes. Both in solution and
      solid state, the photoluminescence spectra shows that emission is significantly
      red-shifted in the [Ir(F2ppy)2(ppz)][PF6] complex compared with the
      [Ir(F2ppy)2(ppl)][PF6] complex. Besides, the [Ir(F2ppy)2(ppl)][PF6] complex
      exhibits a higher quantum yield and a longer excited state lifetime than the
      [Ir(F2ppy)2(ppz)][PF6] complex; therefore, in the last case non-radiative decay
      is predominant due to the stabilization of LUMO orbital (energy gap law). In the
      fabrication of LEC devices with the [Ir(F2ppy)2(ppl)][PF6] complex, light
      emission was obtained with a maximum value of luminance equal to 177 cd m(-2),
      while in the case of the [Ir(F2ppy)2(ppz)][PF6] complex, no luminance was
      observed. According to the photophysical data, the performance in LEC devices
      could be explained by the different position of the nitrogens in the ppl and ppz
      structural isomers, electronically affecting the complex, and therefore its
      properties. In addition, from the crystallographic analysis it is possible to
      note that the [Ir(F2ppy)2(ppz)][PF6] complex shows enhanced intermolecular and
      intramolecular interactions compared with [Ir(F2ppy)2(ppl)][PF6], and
      consequently a higher ordering of the molecules in the complex with ppz ligand
      can be expected. This higher order could favour the quenching processes, and
      consequently enhance the non-radiative deactivation. 

PMID- 26219435
TI  - Prediction of the 10-year probability of gastric cancer occurrence in the
      Japanese population: the JPHC study cohort II.
AB  - Gastric cancer is a particularly important issue in Japan, where incidence rates
      are among the highest observed. In this work, we provide a risk prediction model
      allowing the estimation of the 10-year cumulative probability of gastric cancer
      occurrence. The study population consisted of 19,028 individuals from the
      Japanese Public Health Center cohort II who were followed-up from 1993 to 2009. A
      parametric survival model was used to assess the impact on the probability of
      gastric cancer of clinical and lifestyle-related risk factors in combination with
      serum anti-Helicobacter pylori antibody titres and pepsinogen I and pepsinogen II
      levels. Based on the resulting model, cumulative probability estimates were
      calculated and a simple risk scoring system was developed. A total of 412 cases
      of gastric cancer occurred during 270,854 person-years of follow-up. The final
      model included (besides the biological markers) age, gender, smoking status,
      family history of gastric cancer and consumption of highly salted food. The
      developed prediction model showed good predictive performance in terms of
      discrimination (optimism-corrected c-index: 0.768) and calibration (Nam and
      d'Agostino's chi(2) test: 14.78; p values = 0.06). Estimates of the 10-year
      probability of gastric cancer occurrence ranged from 0.04% (0.02, 0.1) to 14.87%
      (8.96, 24.14) for men and from 0.03% (0.02, 0.07) to 4.91% (2.71, 8.81) for
      women. In conclusion, we developed a risk prediction model for gastric cancer
      that combines clinical and biological markers. It might prompt individuals to
      modify their lifestyle habits, attend regular check-up visits or participate in
      screening programmes.

PMID- 26219439
TI  - A call-to-action from the feedM.E. Middle East study group. Use of a screen
      intervene-supervene strategy to address malnutrition in healthcare.
AB  - Up to 50% of hospitalized patients worldwide are malnourished or at risk of
      malnutrition. Guidelines recommend nutritional screening of all patients on
      hospital admission. Results from studies of hospitalized patients show that
      screening, with follow-up nutritional assessment and care when indicated, can
      improve patients' clinical outcomes and reduce healthcare costs. Despite
      compelling evidence, attention to nutritional care remains suboptimal in clinical
      settings worldwide. The feedM.E. Global Study Group developed a simple, stepwise
      Nutrition Care Pathway to facilitate best-practice nutrition care. This pathway
      guides clinicians to screen patients' nutritional status on hospital admission or
      at initiation of care; intervene promptly with nutrition care when needed; and
      supervene or follow-up routinely with adjustment and reinforcement of nutrition
      care plans. The feedM.E. Middle East Study Group seeks to extend this program to
      our region. We advise clinicians to adopt and adapt the Nutrition Care Pathway,
      bringing quality nutrition care to everyday practice. 

PMID- 26219440
TI  - Long-term compliance with continuous positive airway pressure in Saudi patients
      with obstructive sleep apnea. A prospective cohort study.
AB  - OBJECTIVES: To evaluate continuous positive airway pressure (CPAP) compliance and
      define predictors of CPAP compliance among Saudi patients with obstructive sleep
      apnea (OSA) after applying an educational program.  METHODS: This prospective
      cohort study included consecutive patients diagnosed to have OSA based on
      polysomnography between January 2012 and January 2014 in King Saud University,
      Riyadh, Kingdom of Saudi Arabia. All patients had educational sessions on OSA and
      CPAP therapy before sleep study, and formal hands-on training on CPAP machines on
      day one, day 7, and day 14 after diagnosis. The follow-up in the clinic was
      carried out at one, 4, and 10 months after initiating CPAP therapy. Continuous
      positive airway pressure compliance was assessed objectively. Logistic regression
      model was used to assess the predictors of CPAP adherence. RESULTS: The study
      comprised 156 patients with a mean age of 51.9+/-12.1 years, body mass index of
      38.4+/-10.6 kg/m2, and apnea hypopnea index of 63.7+/-39.3 events/hour. All
      patients were using CPAP at month one, 89.7% at month 4, and 83% at month 10. The
      persistence of CPAP-related side effects and comorbid bronchial asthma remained
      as independent predictors of CPAP compliance at the end of the study. CONCLUSION:
      With intensive education, support, and close monitoring, more than 80% of Saudi
      patients with OSA continued to use CPAP after 10 months of initiating CPAP
      therapy.

PMID- 26219441
TI  - Prevalence and predictors of habitual snoring in a sample of Saudi middle-aged
      adults.
AB  - OBJECTIVES: To determine the prevalence of habitual snoring among a sample of
      middle-aged Saudi adults, and its potential predictors.  METHODS: A cross
      sectional study was conducted from March 2013 until June 2013 in randomly
      selected Saudi Schools in Jeddah, Kingdom of Saudi Arabia. The enrolled subjects
      were 2682 school employees (aged 30-60 years, 52.1% females) who were randomly
      selected and interviewed. The questionnaire used for the interview included: the
      Wisconsin Sleep Questionnaire to assess for snoring, medical history, and socio
      demographic data. Anthropometric measurements and blood pressure readings were
      recorded using standard methods.  RESULTS: Forty percent of the 2682 enrolled
      subjects were snorers: 23.5% were habitual snorers, 16.6% were moderate snorers,
      and 59.9%, were non-snorers. A multivariate analysis revealed that independent
      predictors of snoring were ageing, male gender, daytime sleepiness, hypertension,
      family history of both snoring and obstructive sleep apnea, water-pipe smoking,
      and consanguinity. CONCLUSION: This study shows that snoring is a common
      condition among the Saudi population. Previously reported risk factors were
      reemphasized but consanguinity was identified as a new independent predictive
      risk factor of snoring. Exploring snoring history should be part of the clinical
      evaluation.

PMID- 26219442
TI  - Pulmonary function indices in children with sickle cell anemia in Enugu, south
      east Nigeria.
AB  - OBJECTIVES: To determine the pulmonary function indices of children with sickle
      cell anemia (SCA) attending the pediatric sickle cell clinic at the University of
      Nigeria Teaching Hospital, Enugu, south-east Nigeria and to compare these indices
      with the results obtained from other regions.  METHODS: A case control study of
      lung function in children with SCA aged 6-20 years. The study was carried out in
      the University of Nigeria/University of Nigeria Teaching Hospital, Enugu State,
      Nigeria between October 2014 and January 2015. Measurements of the peak
      expiratory flow rate, forced vital capacity (FVC), and forced expiratory volume
      in one second (FEV1) were evaluated. RESULTS: A total of 80 subjects were
      recruited into the study, comprising 40 homozygous HbSS (hemoglobin SS) patients
      and an equal number of controls. Children with SCA had statistically lower values
      of FEV1 (1.6+/-0.52), FVC (1.76+/-0.95), and peak expiratory flow rate (PEFR)
      (309.00+/-82.64) when compared with normal hemoglobin genotype FEV1 (12.01+/
      0.53), FVC (2.12+/-0.54), and PEFR (364.10+/-87.85). The mean FVC, FEV1/FVC, and
      PEFR were also higher in the male control group compared with the HbSS male
      group, but these differences were not statistically significant. Female controls
      had significantly larger FEV1, FVC, and PEFR values compared with the HbSS
      females.  CONCLUSION: The lung function indices were significantly lower in
      children and adolescents with SCA compared with the matched controls with a
      hemoglobin genotype AA.

PMID- 26219443
TI  - Thrombus aspiration during primary percutaneous coronary intervention associated
      with reduced platelet activation.
AB  - OBJECTIVES: To determine the effect of thrombectomy on platelet function in
      patients undergoing primary percutaneous coronary intervention (PPCI) for ST
      segment elevation myocardial infarction (STEMI). METHODS: This retrospective
      study included 413 consecutive STEMI patients who underwent PPCI between March
      2012 and September 2013 at Kartal Kosuyolu High Specialty Education and Research
      Hospital, Istanbul, Turkey that were assigned to the thrombus aspiration (TA)
      group or the non-TA group. Platelet count and mean platelet volume (MPV) were
      obtained at baseline and 24 hours (h), 48 h, and 72 h post PPCI. RESULTS:
      Baseline MPV was similar in both groups, whereas the baseline platelet count was
      higher in the TA group (p=0.42 and p=0.002). The platelet count was higher in the
      TA group 24 h post PPCI (p=0.02), but was similar in both groups 48 h and 72 h
      post PPCI (p=0.18 and p=0.07). The MPV 48 h and 72 h post PPCI was higher in the
      non-TA group than in the TA group (8.4 +/- 1.3 fL versus 8.7 +/- 1.6 fL [p=0.04]
      and 8.5 +/- 1.1 fL versus 8.9 +/- 1.5 fL [p=0.04]). CONCLUSION: Thrombectomy
      reduced platelet activity via removal of thrombi from the coronary arteries in
      patients undergoing PPCI for STEMI.

PMID- 26219444
TI  - Independent risk factors for hypoxemia after surgery for acute aortic dissection.
AB  - OBJECTIVES: To determine risk factors associated with postoperative hypoxemia
      after surgery for acute type A aortic dissection. METHODS: We retrospectively
      analyzed the clinical data of 192 patients with acute type A aortic dissection
      who underwent surgery in Qingdao Municipal Hospital, Medical College of Qingdao
      University, Qingdao, China between January 2007 and December 2013. Patients were
      divided into hypoxemia group (n=55) [arterial partial pressure of oxygen
      (PaO2)/fraction of inspired oxygen (FiO2) <= 200 mm Hg] and non-hypoxemia group
      (n=137) [PaO2/FiO2 > 200 mm Hg]. Perioperative clinical data were analyzed and
      compared between the 2 groups. RESULTS: The incidence of postoperative hypoxemia
      after surgery for acute aortic dissection was 28.6% (55/192). Perioperative death
      occurred in 13 patients (6.8%). Multivariate regression identified body mass
      index (BMI) > 25 kg/m2 (OR=21.929, p=0.000), deep hypothermic circulatory arrest
      (DHCA) (OR=11.551, p=0.000), preoperative PaO2/FiO2 <= 300 mm Hg (OR=7.830,
      p=0.000) and blood transfusion > 6U in 24 hours postoperatively (OR=12.037,
      p=0.000) as independent predictors of postoperative hypoxemia for patients
      undergoing Stanford A aortic dissection surgery. CONCLUSION: Our study
      demonstrated that BMI > 25 kg/m2, DHCA, preoperative PaO2/FiO2 <= 300 mm Hg, and
      blood transfusion in 24 hours postoperatively > 6U were independent risk factors
      of the hypoxemia after acute type A aortic dissection aneurysm surgery.

PMID- 26219445
TI  - Neonatal short-term outcomes in infants with intrauterine growth restriction.
AB  - OBJECTIVES: To assess the neonatal outcomes in newborns with intrauterine growth
      restriction (IUGR) in a Romanian population in a 3 level maternity unit. METHODS:
      A matched case-control design, with one control for each patient was used. The
      case group comprised neonates with birth weight and birth length below the 10th
      percentile for the gestational age. Individual matching by gender and age of
      gestation was used to identify the control group. Both cases and controls were
      selected from the infants admitted to and discharged from the Neonatal Ward, at
      the First Gynecology Clinic, of the County Emergency Hospital Cluj-Napoca, Cluj
      Napoca, Romania, between January 2012 and June 2014. RESULTS: One hundred and
      forty-two subjects were included in each group. The cesarean delivery was
      significantly more frequent in the IUGR group (66.9%) compared with controls
      (46.5%; p=0.0006). The Apgar score at one minute was >= 7 for most infants in
      both groups (77.9% IUGR group versus 77.5% control group), with no significant
      differences between the groups. A significantly higher percentage of infants in
      the IUGR group had hypoglycemia or intraventricular hemorrhage compared with the
      controls (p < 0.05). Hypoglycemia proved a significant factor for IUGR (odds
      ratio = 4.763, 95% confidence interval: 1.711-13.255). CONCLUSION: Hypoglycemia
      and intraventricular hemorrhage characterized the IUGR newborns.

PMID- 26219446
TI  - Effects of occupational therapy on quality of life of patients with metastatic
      prostate cancer. A randomized controlled study.
AB  - OBJECTIVES: To evaluate the efficiency of occupational therapy relative to a home
      program in improving quality of life (QoL) among men who were treated for
      metastatic prostate cancer (MPC). METHODS: Fifty-five men were assigned randomly
      to either the 12-week cognitive behavioral therapy based occupational therapy (OT
      CBSM) intervention (treatment group) or a home program (control group) between
      March 2012 and August 2014 in the Department of Occupational Therapy, Faculty of
      Health Sciences, Hacettepe University, Ankara, Turkey. The Canadian Occupational
      Performance Measure (COPM) was used to measure the occupational performance and
      identify difficulties in daily living activities. The QoL and symptom status were
      measured by The European Organization for Research and Treatment of Cancer Core
      Quality of Life Questionnaire C30 and its Prostate Cancer Module. A 12-week OT
      CBSM intervention including client-centered training of daily living activities,
      recreational group activities, and cognitive behavioral stress management
      intervention were applied. RESULTS: The COPM performance and satisfaction scores,
      which indicate occupational participation and QoL increased statistically in the
      treatment group in relation to men who were included in the home-program (p less
      than or equal to 0.05). CONCLUSION: A 12-week OT-CBSM intervention was effective
      in improving QoL in men treated for MPC, and these changes were associated
      significantly with occupational performance.

PMID- 26219447
TI  - Diseases pattern among patients attending Holy Mosque (Haram) Medical Centers
      during Hajj 1434 (2013).
AB  - OBJECTIVE: To evaluate the diseases pattern among pilgrims attending the 2 Holy
      Mosque (Haram) Health Care Centers during the Hajj season 2013 (Hijra 1434). 
      METHODS: In this cross-sectional study, data was collected from 2 medical centers
      located in the Holy Mosque in Makkah city, Saudi Arabia, from the first of Dhul
      Hijjah to sixteenth Dhul-Hijjah 1434. The present study was completed in 16 days
      (6th October to 21st October 2013). RESULTS: Over 16 days, 1008 patients attended
      the medical centers during Hajj 1434, (2013), out of which 554 (55%) were males
      and 454 (45%) were females. Most of the patients were Egyptians (n=242, 24%),
      followed by Saudis (n=116, 11.5%), Pakistani (n=114, 11.3%), Turkish (n=50, 5%),
      and other nationalities (n=404). According to age distribution, mostly were in
      the 51-60 years age group (n=237, 23.5%), followed by other age groups. Out of
      1008 patients, 842 (83.5%) patients were treated and subsequently discharged,
      while 166 patients (16.5%) were referred to the tertiary centers. According to
      the diseases pattern, most of the patients were suffering from respiratory
      problems (n=177, 17.6%) followed by skin diseases (n=158, 15.7%),
      gastrointestinal tract (GIT) diseases (n=133, 13.2%), and others. CONCLUSION:
      Most of the patients were suffering from respiratory problems followed by skin
      and GIT diseases, and less than 25% of patients were referred to tertiary care
      centers.

PMID- 26219448
TI  - Ultrasonographic assessment of splenic volume and its correlation with body
      parameters in a Jordanian population.
AB  - OBJECTIVES: To estimate normal linear dimensions and volume of spleen in
      Jordanians using ultrasonography, and to correlate splenic volume with age and
      body parameters: height, weight, body surface area (BSA), and body mass index
      (BMI). METHODS: A prospective pilot study was conducted on 205 volunteers (115
      males and 90 females) not known to have any conditions likely to be associated
      with splenomegaly. The study was performed at the Radiology Department, Jordanian
      University Hospital, Amman, Jordan, between December 2013 and August 2014. All
      linear dimensions of spleen were measured, and splenic volume (index) was
      calculated using the standard prolate ellipsoid formula (length * width * depth *
      0.523). The splenic volume was then analyzed with age and body parameters using
      the Pearson's correlation coefficient. RESULTS: The mean (+/- SD) splenic
      dimensions were 10.72+/-1.37 cm in length, 7.40+/-1.52 cm in width, 4.40+/-1.47
      cm in depth, and 184.15+/-79.56 cm3 in volume. Men had larger spleens than women
      (p less than 0.0001). Age had no significant effect on spleen volume (r=0.11,
      p=0.12). There was a significant moderate positive correlation (p less than
      0.0001), using Pearson's correlation coefficient, between the spleen volume, and
      other parameters (height, weight, BSA, and BMI), with correlation coefficients
      exceeding 0.3. CONCLUSION: A local reference of spleen dimensions was established
      with a different range of values reported previously.

PMID- 26219449
TI  - Radiographic assessment of impacted teeth and associated pathosis prevalence.
      Pattern of occurrence at different ages in Saudi male in Western Saudi Arabia.
AB  - OBJECTIVES: To assess the prevalence of both impaction and associated pathosis in
      a Saudi population in Al-Madinah, Saudi Arabia based on digital panoramic
      radiographs. METHODS: This study was carried out from December 2013 to February
      2015. Panoramic radiographs of 359male patients attending the Oral Diagnosis
      Clinics, Faculty of Dentistry, Taibah University, Al-Madinah, Saudi Arabia were
      reviewed. All images were evaluated to determine the prevalence and pattern of
      impacted third molars and canines, and associated pathosis. RESULTS: Among 359
      panoramic radiographs examined, 124 patients had impacted teeth. The impacted
      mandibular third molars were the most prevalent impacted teeth, 77.6% had class
      II pattern of impaction. Among the impacted maxillary canines, 75% were
      mesioangular and among 66 impacted maxillary third molars, 63.6% had class C. Our
      study showed that 5.8% of Saudi patients had 3 or more impacted teeth, 13.1% had
      2 impacted teeth, and 15.6% had one impacted tooth. Associated pathosis was found
      in 18.2% among impacted maxillary third molars, and 31.5% among impacted
      mandibular third molars. The incidence of impaction decreases with age. 
      CONCLUSION: The prevalence and pattern of impacted third molars among Saudis are
      almost similar to other racial populations. The number of missing wisdom
      increases with age. Although the percentage of pathosis associated with impaction
      was considerably low, it is essential to carry you regular oral examinations to
      preserve asymptomatic impacted teeth in good health.

PMID- 26219450
TI  - A novel missense mutation in the TBX5 gene in a Saudi infant with Holt-Oram
      syndrome.
AB  - We report on a Saudi infant with Holt-Oram syndrome caused by a de novo missense
      mutation of the TBX5 gene. The mutation (Thr72Lys) is novel and has not been
      previously reported. The cardiac and limb defects in our patient were both
      severe, and the infant also had micrognathia and cleft palate. Previously
      reported cases of the Holt-Oram syndrome caused by missense mutations were
      reviewed and their phenotypes were compared with the phenotype of our patient. 

PMID- 26219451
TI  - An unusual outcome of a giant ventral hernia.
AB  - Hernias are routine general surgical problems that may present in any age group,
      regardless of the patient's socioeconomic status. We present a rare case of a
      complicated ventral hernia leading to short bowel. This is an unusual case and is
      very rarely reported in the literature. This current case report describes a 54
      year-old gentleman who presented to the hospital with a giant strangulated
      ventral hernia causing massive bowel ischemia and resulting in a short bowel. The
      literature on large abdominal wall hernias leading to short bowel is reviewed,
      and a discussion on short bowel syndrome is also presented. 

PMID- 26219452
TI  - Combined orthodontic and periodontic treatment in a child with Papillon Lefevre
      syndrome.
AB  - A 9-year-old girl with Papillon-Lefevre syndrome (PLS) was treated
      orthodontically 24 months after the start of mechanical and antibiotic therapy in
      adjunct with periodontal treatment every 6 weeks. After achieving stable
      periodontal conditions, orthodontic treatment was commenced to correct the teeth
      position, facial profile, and maxillary protraction. Following the combination
      therapy and a failure to detect Actinobacillus actinomycetemcomitans from any
      site in the oral cavity, orthodontic treatment with a fixed appliance was
      performed aside from creating space for eruption of permanent teeth. We found
      that combined periodontal and orthodontic treatment of PLS may be successful with
      a complex interdisciplinary regimen and close follow up. This is a 2-year follow
      up case report of a girl with PLS. Orthodontic and periodontic therapy were
      offered using combined treatments of orthodontic and periodontal with the benefit
      of prosthodontic consultation, resulting in a treatment plan. 

PMID- 26219453
TI  - Comparison of posterior versus transforaminal lumbar interbody fusion using
      finite element analysis. Influence on adjacent segmental degeneration.
AB  - OBJECTIVES: To compare the influence of posterior lumbar interbody fusion (PLIF)
      and transforaminal lumbar interbody fusion (TLIF) on adjacent segment
      degeneration (ASD). METHODS: The study was carried out in the Traumatology and
      Orthopedics Laboratory, Department of Traditional Chinese Medicine, Medical
      School, Jinan University, Guangzhou, China, between December 2013 and November
      2014. A normal, healthy finite element model of L3-5 was developed, a PLIF and a
      TLIF model were modified from the normal model, and interbody fusions were
      performed in the L4-5 segment. An 800 N compressive loading plus 10 Nm moments
      simulating flexion, extension, lateral bending, and axial rotation were imposed
      on the L3 superior endplate. Intradiscal pressure and intersegmental rotation in
      L3-4 were investigated. RESULTS: The values of intradiscal pressure and
      intersegmental rotation in the PLIF or TLIF model were higher than those in the
      normal, healthy model, but the values in the TLIF model were relatively lower
      than those in the PLIF model in all directions.  CONCLUSION: Posterior lumbar
      interbody fusion has more adverse influence on the superior adjacent segment than
      TLIF.

PMID- 26219454
TI  - Evaluating the therapeutic efficacy, tolerability, and safety of an aqueous
      extract of Costus speciosus rhizome in acute pharyngitis and acute tonsillitis. A
      pilot study.
AB  - OBJECTIVES: To determine the efficacy, tolerability, and safety of an aqueous
      extract of Costus speciosus (C. speciosus) rhizome in pediatric and adult
      patients suffering from acute pharyngitis and tonsillitis as an alternative to
      antibiotics use. METHODS: This pilot cohort trial was conducted at King Abdulaziz
      University in Saudi Arabia between May and December 2014, among 15 patients with
      acute pharyngitis and tonsillitis who were administered nasal drops of aqueous
      extract of C. speciosus rhizome at a dose of 15-30 drops every 8 hours for 3
      days. The primary outcome measure was the clinical improvement and remission rate
      within the first 5 days. RESULTS: The administration of C. speciosus resulted in
      an improvement in acute symptoms in 60% of the patients treated within the first
      24 hours, and remission rate of 93% by day 5, without any recorded adverse
      effects. CONCLUSION: This study revealed a significant efficacy of the aqueous
      extract of C. speciosus rhizome in acute pharyngitis and tonsillitis.

PMID- 26219455
TI  - Bowel obstruction in elderly lady.

PMID- 26219456
TI  - The Saudi Clinical Practice Guideline for the treatment of venous
      thromboembolism. Outpatient versus inpatient management.
AB  - Venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary
      embolism (PE) is commonly encountered in daily clinical practice. After
      diagnosis, its management frequently carries significant challenges to the
      clinical practitioner. Treatment of VTE with the inappropriate modality and/or in
      the inappropriate setting may lead to serious complications and have life
      threatening consequences. As a result of an initiative of the Ministry of Health
      of the Kingdom of Saudi Arabia, an expert panel led by the Saudi Association for
      Venous Thrombo-Embolism (a subsidiary of the Saudi Thoracic Society) and the
      Saudi Scientific Hematology Society with the methodological support of the
      McMaster University Guideline working group, this clinical practice guideline was
      produced to assist health care providers in VTE management. Two questions were
      identified and were related to the inpatient versus outpatient treatment of acute
      DVT, and the early versus standard discharge from hospital for patients with
      acute PE. The corresponding recommendations were made following the GRADE
      (Grading of Recommendations, Assessment, Development, and Evaluation) approach. 

PMID- 26219457
TI  - Leishmaniasis, malaria, and schistosomiasis concurrently in an 8-year-old boy.

PMID- 26219458
TI  - Chemical generation and modification of peptides containing multiple
      dehydroalanines.
AB  - Chemical formation of dehydroalanine has been widely used for the post
      translational modification of proteins and peptides, however methods to
      incorporate multiple dehydroalanine residues into a single peptide have not been
      defined. We report the use of methyl 2,5-dibromovalerate which can be used to
      cleanly carry out this transformation. 

PMID- 26219459
TI  - Short-term effects of intragastric balloon in association with conservative
      therapy on weight loss: a meta-analysis.
AB  - Obesity is an epidemic chronic disease which is a risk factor for a number of
      serious medical conditions. Intragastric balloon, as an alternative, non-surgical
      treatment approach for the management of obesity, was rejected in previous
      evidence-based reviews. The object of this review is updating the data and
      confirming the safety and efficacy of the procedure. In this review, systematic
      literature retrieve of MEDLINE, EMBASE, CENTRAL and other information sources was
      performed from inception to December 2014. The quality of selected studies was
      assessed and meta-analyses of weighted mean differences were made using the
      inverse variance method. Meta-analyses presented significant effect sizes of -8.9
      kg, -3.1 kg/m(2) and -21.0% for SMG as well as of -1.5 kg and -1.2 kg/m(2) for
      LSG, favoring the intervention group. Safety analysis showed that minor
      complications occurred at a high rate in intervention group, however, no serious
      or fatal complication was reported in these studies. In conclusion, the current
      review presents that short-term efficacy for 6 months treatment of intragastric
      balloon in association with conservative therapy is clinically significant.

PMID- 26219460
TI  - Effect of maternal gestational weight gain on offspring DNA methylation: a follow
      up to the ALSPAC cohort study.
AB  - BACKGROUND: Several epidemiologic studies indicate that maternal gestational
      weight gain (GWG) influences health outcomes in offspring. Any underlying
      mechanisms have, however, not been established. A recent study of 88 children
      based on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort
      examined the methylation levels at 1,505 Cytosine-Guanine methylation (CpG) loci
      and found several to be significantly associated with maternal weight gain
      between weeks 0 and 18 of gestation. Since these results could not be replicated
      we wanted to examine associations between 0 and 18 week GWG and genome-wide
      methylation levels using the Infinium HumanMethylation450 BeadChip (450K)
      platform on a larger sample size, i.e. 729 newborns sampled from the Norwegian
      Mother and Child Cohort Study (MoBa). RESULTS: We found no CpG loci associated
      with 0-18 week GWG after adjusting for the set of covariates used in the ALSPAC
      study (i.e. child's sex and maternal age) and for multiple testing (q > 0.9, both
      1,505 and 473,731 tests). Hence, none of the CpG loci linked with the genes found
      significantly associated with 0-18 week GWG in the ALSPAC study were significant
      in our study. CONCLUSIONS: The inconsistency in the results with the ALSPAC study
      with regards to the 0-18 week GWG model may arise for several reasons: sampling
      from different populations, dissimilar methylome coverage, sample size and/or
      false positive findings.

PMID- 26219461
TI  - Stay calm! Regulating emotional responses by implementation intentions: Assessing
      the impact on physiological and subjective arousal.
AB  - Implementation intention (IMP) has recently been highlighted as an effective
      emotion regulatory strategy. Most studies examining the effectiveness of IMPs to
      regulate emotion have relied on self-report measures of emotional change. In two
      studies we employed electrodermal activity (EDA) and heart rate (HR) in addition
      to arousal ratings (AR) to assess the impact of an IMP on emotional responses. In
      Study 1, 60 participants viewed neutral and two types of negative pictures
      (weapon vs. non-weapon) under the IMP "If I see a weapon, then I will stay calm
      and relaxed!" or no self-regulatory instructions (Control). In Study 2,
      additionally to the Control and IMP conditions, participants completed the
      picture rating task either under goal intention (GI) to stay calm and relaxed or
      warning instructions highlighting that some pictures contain weapons. In both
      studies, participants showed lower EDA, reduced HR deceleration and lower AR to
      the weapon pictures compared to the non-weapon pictures. In Study 2, the IMP was
      associated with lower EDA compared to the GI condition for the weapon pictures,
      but not compared to the weapon pictures in the Warning condition. ARs were lower
      for IMP compared to GI and Warning conditions for the weapon pictures. 

PMID- 26219462
TI  - Extracellular milieu grossly alters pathogen-specific immune response of mammary
      epithelial cells.
AB  - BACKGROUND: Considerably divergent data have been published from attempts to
      model the E. coli vs. S. aureus specific immune reaction of the udder using
      primary cultures of bovine mammary epithelial cells from cows (pbMEC). Some
      groups reported a swift, strong and transient inflammatory response against
      challenges with E. coli and only a weak and retarded response against S. aureus,
      in agreement with the respective reaction of the udder. Others found almost the
      reverse. Presence or absence of fetal calf serum distinguished the experimental
      setting between both groups. We examined here if this causes the divergent
      reaction of the pbMEC towards both pathogen species. We challenged pbMEC with
      proteins from heat killed E. coli or S. aureus pathogens or purified TLR2 and
      TLR4 ligands. The stimuli were applied in normal growth medium with (SM10) or
      without (SM0) 10% fetal calf serum, or in the basal medium supplemented with 10
      mg/ml milk proteins (SM Milk). RESULTS: Withdrawal of FCS slowed down and
      decreased the extent by which E. coli or LPS enhanced the expression of cyto- and
      chemokine encoding genes through impaired TLR4 signalling but enforced their
      expression during stimulation with S. aureus. SM Milk strongly quenched the
      induction of those genes. S. aureus strain specific differences in the reaction
      of the pbMEC could only be recorded in SM0. NF-kappaB factors were activated by
      E. coli in all stimulation media, but only to a small extent by S. aureus, solely
      in SM0. Purified ligands for TLR2 stimulated expression of those genes and
      activated NF-kappaB equally well in SM10 and SM0. The mRNA destabilizing factor
      tristetraproline was only induced by E. coli in SM10 and by purified PAMPs.
      CONCLUSIONS: Our data cross validate the correctness of previously published
      divergent data on the pathogen-specific induction of key immune genes in pbMEC.
      The differences are due to the presence of FCS, modulating signalling through
      TLR4 and TLR-unrelated pathogen receptors. S. aureus does not substantially
      activate any TLR signalling in MEC. Rather, receptors distinct from TLRs perceive
      the presence of S. aureus and control the immune response against this pathogen
      in MEC.

PMID- 26219464
TI  - Predictors of resilience among adolescents of low socio-economic status in India.
AB  - This study examined the predictors of resilience among adolescents of low socio
      economic status (SES). Cross-sectional data were obtained from 1451 adolescent
      students (girls = 718) of low SES aged 14 to 19 years in rural public schools.
      Students completed a set of self-report measures relating to temperament familiar
      in Indian culture (sattvic, rajasic and tamasic gunas), intrinsic and extrinsic
      aspirations, academic aspiration, and perceived school environment. Resilience
      was operationalized as a composite derived from academic grades and scores on the
      Subjective Well-Being Inventory. Regression analysis revealed that sattvic,
      rajasic and tamasic self-concepts were significant predictors of resilience.
      Resilience was negatively predicted by both rejection experienced in the school
      environment and extrinsic aspirations. The findings have implications for policy
      and intervention for adolescent students in rural schools of low socio-economic
      backgrounds. 

PMID- 26219463
TI  - T cells are functionally not impaired in AML: increased PD-1 expression is only
      seen at time of relapse and correlates with a shift towards the memory T cell
      compartment.
AB  - BACKGROUND: T cell function is crucial for the success of several novel
      immunotherapeutic strategies for the treatment of acute myeloid leukemia (AML).
      However, changes in phenotype and function of T cells have been described in
      various hematologic malignancies, mimicking T cell exhaustion known from chronic
      viral infections. Detailed knowledge about phenotype and function of T cells in
      AML patients at different stages of the disease is indispensable for optimal
      development and application of immunotherapeutic strategies for this disease.
      METHODS: We used flow cytometry-based assays to characterize T cell phenotype and
      function in peripheral blood and bone marrow of AML patients at diagnosis, at
      relapse after intensive chemotherapy, and at relapse after allogeneic stem cell
      transplantation (SCT). Surface expression of CD244, PD-1, CD160, and TIM-3 was
      determined, and proliferation and production of IFN-gamma, TNF-alpha, and IL-2
      were measured. RESULTS: We detected similar expression of inhibitory molecules on
      T cells from patients at diagnosis and from age-matched healthy controls. At
      relapse after SCT, however, PD-1 expression was significantly increased compared
      to diagnosis, both on CD4(+) and CD8(+) T cells. This pattern was not associated
      with age and cytomegalovirus (CMV) status but with a shift towards effector
      memory cells in relapsed AML patients. Proliferation and cytokine production
      assays did not reveal functional defects in T cells of AML patients, neither at
      diagnosis nor at relapse. CONCLUSION: We thus conclude that T cell exhaustion
      does not play a major role in AML. Immunotherapeutic strategies targeting
      autologous T cells thus have particularly good prospects in the setting of AML.

PMID- 26219466
TI  - The APC/C and CK1 in the developing brain.

PMID- 26219465
TI  - Influence of ethnicity on the distribution of genetic polymorphisms associated
      with risk of chronic liver disease in South American populations.
AB  - BACKGROUND: The global burden of chronic liver disease is rising. Besides
      environmental, behavioral, viral and metabolic factors, genetic polymorphisms in
      patatin-like phospholipase-3 (PNPLA3) and vitamin D receptor (VDR) genes have
      been related to the development of chronic liver disease and progression towards
      liver cancer. Although their prevalence differs remarkably among ethnic groups,
      the frequency of these polymorphisms in South American populations -whose genetic
      background is highly admixed- has been poorly studied. Hence, the aim of this
      study was to characterize polymorphisms related to chronic liver disease and
      their association with the genetic ancestry of South American populations.
      RESULTS: DNA samples from 258 healthy unrelated male volunteers were analyzed.
      The frequencies of G and C alleles of rs738409 polymorphism (PNPLA3 gene) were 74
      % and 26 %, respectively; whereas the bAt (CCA) haplotype (VDR gene) was observed
      in 32.5 % of the samples. The GG genotype of PNPLA3 rs738409 and the bAt (CCA)
      haplotype -associated with an increased risk of chronic liver disease and
      progression towards liver cancer- were significantly more frequent among samples
      exhibiting maternal and paternal Native American haplogroups (63.7 % and 64.6 %),
      intermediate among admixed samples (45.1 % and 44.9 %; p = 0.03) and the lowest
      for Non-native American ancestry (30.1 % and 29.6 %; p = 0.001 and p = 0.0008).
      CONCLUSIONS: These results suggest that individuals with Native American ancestry
      might have a high risk of chronic liver disorders and cancer. Furthermore, these
      data not only support the molecular evaluation of ancestry in multi-ethnic
      population studies, but also suggest that the characterization of these variants
      in South American populations may be useful for establishing public health
      policies aimed at high risk ethnic communities.

PMID- 26219467
TI  - LKB1 in transmembrane receptor signaling.

PMID- 26219468
TI  - Sirtuin 3 in acute kidney injury.

PMID- 26219469
TI  - miR-24 in diabetes.

PMID- 26219470
TI  - Physiologically distinct neuronal type in primate cortex.

PMID- 26219472
TI  - Urinary cytology in bladder cancer: why is it still relevant?
AB  - Bladder carcinoma is the most common malignancy of the urinary tract and
      cystoscopy with cytology is currently considered the gold standard for the
      detection and surveillance of primary tumors and for the follow-up of patients
      after transurethral resection. Even if cytology has a low sensitivity especially
      in low-grade bladder carcinomas, the high specificity and the inexpensive nature
      of the equipment required, justify performing it. The greatest value of cytology
      for patients with low-grade, nonmuscle-invasive bladder cancer (NMIBC) is the
      detection of those lesions that may progress to high-grade urothelial carcinoma.

PMID- 26219471
TI  - Superior efficacy of rituximab-based chemoimmunotherapy as an initial therapy in
      newly diagnosed patients with B cell indolent lymphomas: long-term results from a
      single center in China.
AB  - BACKGROUND: Rituximab has been confirmed to improve the survival of patients with
      B cell indolent non-Hodgkin lymphomas (B-iNHLs) in Western world as previously
      reported, however, it is rarely reported in Chinese cohort. This study is to
      investigate the efficacy and safety of rituximab-based chemoimmunotherapy and
      select subpopulations most sensitive to the regimen in Chinese B-iNHL patients.
      METHODS: 334 B-iNHL patients from our center were retrospectively assessed.
      RESULTS: Patients received R-based chemoimmunotherapy showed significantly higher
      rates of overall response (OR) (93.0% vs. 53.4%, P < 0.001) and complete response
      (CR) (63.3% vs. 16.0%, P < 0.001) compared with the patients received other
      therapies. Survival analysis showed that rituximab-based chemoimmunotherapy could
      obviously improve the progression-free survival (PFS) (110 vs. 49 months, P =
      0.001) and overall survival (OS) (120 vs. 72 months, P < 0.001) in patients with
      B-iNHLs. Interestingly, in chronic lymphocytic leukemia (CLL) patients, we found
      that the patients with beta2-microglobulin (beta2-MG) < 3.5 mg/L, lactate
      dehydrogenase (LDH) < 220 U/L, zeta-chain-associated protein kinase 70 (ZAP-70)
      negative, and non high-risk genetic abnormality could achieve more benefits from
      R-based regimens with higher CR rate (P = 0.003, 0.029, 0.013 and 0.038,
      respectively). Meanwhile, more CLL patients achieved minimal residual disease
      (MRD) negative after rituximab-based treatment (46.5% vs. 10.3%, P < 0.001).
      Moreover, CLL patients with MRD < 1%, LDH < 220 U/L, complete remission (CR) or
      partial remission (PR), beta2-MG < 3.5 mg/L and non high-risk cytogenetic
      abnormality showed superior outcome compared to the controls (P = 0.001, 0.000,
      0.000, 0.001 and 0.013, respectively). No other side-effects increased in
      chemoimmunotherapy group except the elevation of grade 3-4 neutropenia.
      CONCLUSIONS: Our results demonstrate the superior efficacy of rituximab-based
      chemoimmunotherapy as an initial therapy in Chinese cohort with newly diagnosed B
      iNHLs and further identify subpopulations that are more sensitive to R-based
      chemoimmunotherapy in CLL group.

PMID- 26219473
TI  - The management of small renal masses: what is likely to change?
AB  - The diffusion of imaging has determined an increased discovery of small renal
      masses (SRMs). Recent publications have been reviewed to present the state of the
      art in the management of SRMs and to try to foresee the next steps in this
      challenging condition. The role of percutaneous biopsies is expanding, since
      management algorithms include also active surveillance and ablative therapies.
      However up to 30% of biopsies fail to provide histological diagnosis and there is
      the risk of under-evaluating high-grade tumors. Active surveillance has been
      proposed in patients with reduced life expectancy and numerous comorbidities. The
      average growth of SRMs is slow, and metastatic progression has been observed in
      about 1%. Ablative therapies (cryotherapy and radiofrequency ablation) are used
      in patients with relevant comorbidities or advanced age and unfit for surgery,
      but who desire active treatment. Compared to conservative surgical treatment both
      techniques have increased local progression rates, while metastatic progression
      is relatively low.Partial nephrectomy (PN) is the recommended curative treatment
      for SRMs and can be performed open, laparoscopically or robotically. Open PN
      represents the benchmark, with similar cancer specific survival and better
      preservation of renal function compared to nephrectomy. Laparoscopy is comparable
      to open surgery in terms of oncologic results, but a long learning curve is
      necessary. Perioperative outcomes of robot-assisted PN appear superior to
      laparoscopy and the learning curve is shorter, but data for oncological results
      are still immature. With the increasing diffusion of robotic technology it is
      likely more SRMs will be managed with this approach.

PMID- 26219475
TI  - Erratum to: teachers' patterns of implementation of an evidence-based
      intervention and their impact on student outcomes: results from a nationwide
      dissemination over 24-months follow-up.

PMID- 26219474
TI  - Enhanced anti-ischemic stroke of ZL006 by T7-conjugated PEGylated liposomes drug
      delivery system.
AB  - The treatment for ischemic stroke is one of the most challenging problems and the
      therapeutic effect remains unsatisfied due to the poor permeation of drugs across
      the blood brain barrier (BBB). In this study, HAIYPRH (T7), a peptide that
      targeted to transferrin receptor (TfR) can mediate the transport of nanocarriers
      across the BBB, was conjugated to liposomes for ischemic stroke targeting
      treatment of a novel neuroprotectant (ZL006). T7-conjugated PEGylated liposomes
      (T7-P-LPs) loaded with ZL006 (T7-P-LPs/ZL006) were showed satisfactory vesicle
      size and size distribution. Furthermore, the cellular uptake results showed that
      T7 modification increased liposomes uptake by the brain capillary endothelial
      cells (BCECs) and little cytotoxicity of liposomes with or without ZL006 was
      observed. The in vivo biodistribution and near-infrared fluorescence imaging
      evidenced that T7 modification rendered liposomes significantly enhanced the
      transport of liposomes across the BBB. The pharmacodynamic study suggested that,
      T7-P-LPs/ZL006 exhibited reduced infarct volume and ameliorated neurological
      deficit compared with unmodified liposomes or free ZL006. T7-P-LPs/ZL006 could be
      targeted to brain and displayed remarkable neuroprotective effects. They could be
      used as a potential targeted drug delivery system of ischemic stroke treatment. 

PMID- 26219476
TI  - Development and functional characterization of alginate dressing as potential
      protein delivery system for wound healing.
AB  - This study aimed to develop and characterize stable films as potential protein
      delivery dressings to wounds. Films were prepared from aqueous gels of sodium
      alginate (SA) and glycerol (GLY) (SA:GLY 1:0, 1:1, 1:2, 2:3, 2:1, 4:3). Purified
      recombinant glutathione-s-transferase (GST), green fluorescent protein (GFP) and
      GST fused in frame to GFP (GST-GFP) (model proteins) were characterized (SDS
      PAGE, Western blotting, immune-detection, and high sensitivity differential
      scanning calorimetry) and loaded (3.3, 6.6 and 30.2mg/g of film) into SA:GLY 1:2
      film. These were characterized using texture analysis, differential scanning
      calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron
      microscopy, swelling, adhesion, dissolution and circular dichroism (CD). The
      protein loaded dressings were uniform, with a good balance between flexibility
      and toughness. The films showed ideal moisture content required for protein
      conformation (TGA), interactions between proteins and film components (DSC),
      indicating stability which was confirmed by CD. Swelling and adhesion showed that
      formulations containing 6.6mg/g of protein possessed ideal characteristics and
      used for in vitro dissolution studies. Protein release was rapid initially and
      sustained over 72h and data fitted to various kinetic equations showed release
      followed zero-order and Fickian diffusion. The results demonstrate the potential
      of SA dressings for delivering therapeutic proteins to wounds. 

PMID- 26219477
TI  - Theme and variations: evolutionary diversification of the HET-s functional
      amyloid motif.
AB  - In mammals and fungi, Nod-like receptors (NLR) activate downstream cell death
      execution proteins by a prion-like mechanism. In Podospora anserina, the NWD2 NLR
      activates the HET-S Helo-domain pore-forming protein by converting its prion
      forming domain into a characteristic beta-solenoid amyloid fold. The amyloid
      forming region of HET-S/s comprises two repetitions of a 21 amino acid motif.
      Herein, we systematically analyze the sequences of C-terminal regions of fungal
      HeLo and HeLo-like domain proteins to identify HET-s-related amyloid motifs
      (HRAM). We now identify four novel HRAM subfamilies in addition to the canonical
      HET-S/s subfamily. These novel motifs share the pseudo-repeat structure of HET
      S/s and a specific pattern of distribution of hydrophobic and polar residues.
      Sequence co-variance analyses predict parallel in-register beta-stacking of the
      two repeats and residue-residue interactions compatible with the beta-solenoid
      fold. As described for HET-S, most genes encoding the HeLo proteins are adjacent
      to genes encoding NLRs also displaying HRAMs. The motifs of the NLRs are similar
      to those of their cognate HeLo-domain protein, indicating concerted evolution
      between repeats. This study shows that HET-s-related amyloid motifs are more
      common than anticipated and that they have diversified into discrete subfamilies
      that apparently share a common overall fold. 

PMID- 26219478
TI  - Cortisol affects metabolic and ionoregulatory responses to a different extent
      depending on feeding ration in common carp, Cyprinus carpio.
AB  - Interacting effects of feeding and stress on corticoid responses in fish were
      investigated in common carp fed 3.0% or 0.5% body mass (BM) which received no
      implant, a sham or a cortisol implant (250 mg/kg BM) throughout a 168 hour post
      implant period (168 h-PI). At 12h-PI, cortisol implants elevated plasma cortisol,
      glucose and lactate. Plasma osmolality and ions remained stable, but cortisol
      increased gill and kidney Na(+)/K(+) ATPase (NKA) and H(+) ATPase activities.
      Gill NKA activities were higher at 3%-BM, whereas kidney H(+) ATPase activity was
      greater at 0.5%-BM. Cortisol induced liver protein mobilization and repartitioned
      liver and muscle glycogen. At 3%-BM, this did not increase plasma ammonia,
      reflecting improved excretion efficiency concomitant with upregulation of Rhesus
      glycoprotein Rhcg-1 in gill. Responses in glucocorticoid receptors (GR1/GR2) and
      mineralocorticoid receptor (MR) to cortisol elevation were most prominent in
      kidney with increased expression of all receptors at 24 h-PI at 0.5%-BM, but only
      GR2 and MR at 0.5%-BM. In the liver, upregulation of all receptors occurred at 24
      h-PI at 3%-BM, whilst only GR2 and MR were upregulated at 0.5%-BM. In the gill,
      there was a limited upregulation: GR2 and MR at 72 h-PI and GR1 at 168 h-PI at 3%
      BM but only GR2 at 72 h-PI at 0.5%-BM. Thus cortisol elevation led to similar
      expression patterns of cortisol receptors in both feeding regimes, while feeding
      affected the type of receptor that was induced. Induction of corticoid receptors
      occurred simultaneously with increases in Rhcg-1 mRNA expression (gill) but well
      after NKA and H(+) ATPase activities increased (gill/kidney).

PMID- 26219479
TI  - The full extent of the global coral reef crisis.

PMID- 26219481
TI  - Acquiring constraints on morphosyntactic variation: children's Spanish subject
      pronoun expression.
AB  - Constraints on linguistic variation are consistent across adult speakers,
      yielding probabilistic and systematic patterns. Yet, little is known about the
      development of such patterns during childhood. This study investigates Spanish
      subject pronoun expression in naturalistic data from 154 monolingual children in
      Mexico, divided into four age groups: 6-7, 8-9, 10-11, 12+. Results from logistic
      regressions examining five predictors of pronoun expression in 6,481 verbs show
      that children's usage is structured and patterned. The study also suggests a
      developmental progression: as children get older, they become sensitive to more
      constraints. I conclude by suggesting that children learn patterns of variation
      by attuning to distributional tendencies in the input, and that the more frequent
      the patterns are, the easier they are to detect and learn. 

PMID- 26219480
TI  - Subdural hematomas: glutaric aciduria type 1 or abusive head trauma? A systematic
      review.
AB  - PURPOSE: Glutaric aciduria type 1 (GA1) is a rare metabolic disorder of glutaryl
      CoA-dehydrogenase enzyme deficiency. Children with GA1 are reported to be
      predisposed to subdural hematoma (SDH) development due to stretching of cortical
      veins secondary to cerebral atrophy and expansion of CSF spaces. Therefore, GA1
      testing is part of the routine work-up in abusive head trauma (AHT). This
      systematic review addresses the coexistence of GA1 and SDH and the validity of
      GA1 in the differential diagnosis of AHT. METHODS: A systematic literature
      review, with language restriction, of papers published before 1 Jan 2015, was
      performed using Pubmed, PsychINFO, and Embase. Inclusion criteria were reported
      SDHs, hygromas or effusions in GA1 patients up to 18 years of age. Of 1599
      publications, 20 publications were included for analysis. RESULTS: In total 20
      cases, 14 boys and 6 girls, were included. In eight cases (40%) a child abuse
      work-up was performed, which was negative in all cases. Clinical history revealed
      the presence of trauma in eight cases (40%). In only one case neuroradiology
      revealed no abnormalities related to GA1 according to the authors, although on
      evaluation we could not exclude AHT. CONCLUSION: From this systematic review we
      conclude that SDHs in 19/20 children with GA1 are accompanied by other brain
      abnormalities specific for GA1. One case with doubtful circumstances was the
      exception to this rule.

PMID- 26219482
TI  - Cirrhosis: A Practical Guide to Management.

PMID- 26219483
TI  - Lynch Syndrome: AGA Patient Guideline Summary.

PMID- 26219484
TI  - A horse in zebra stripes: a peculiar case of undetected end-stage AIDS.
AB  - OBJECTIVE: Late HIV diagnosis occurs in up to 45% of new HIV cases in the
      developed world and is linked to worse health outcomes, including more
      hospitalizations, higher health care resource utilization and less robust
      responses to highly active antiretroviral therapy. METHOD: Case report RESULTS: A
      70-year-old woman with an obscure constellation of medical and psychiatric
      complaints ultimately proved to have end-stage acquired immunodeficiency syndrome
      discovered much too late. Curiously, she had no obvious risk factors for HIV
      infection. CONCLUSION: This tragic case underscores the importance of keeping HIV
      infection in the differential for a patient with diverse vague complaints. Let
      this story caution its readers: when you hear hoof beats, do not look for zebras 
      even when you are least expecting a horse.

PMID- 26219485
TI  - Imported malaria in pregnancy.

PMID- 26219486
TI  - Impact of dabigatran on platelet function and fibrinolysis.
AB  - BACKGROUND: We sought to evaluate the potential enhanced fibrinolytic and
      antiplatelet activity of dabigatran etexilate (DE) due to decreased thrombin
      levels in patients with stroke or transient ischemic attack and non-valvular
      atrial fibrillation (NVAF). METHODS: Consecutive patients with cerebrovascular
      diseases and NVAF that were treated with DE in a tertiary university hospital.
      Fibrinolysis and platelet function were assessed by thromboelastometry (ROTEM)
      and platelet function analyzer (PFA)-100, respectively, before and after
      treatment with DE. Conventional coagulation tests, endogenous thrombin potential
      (ETP) and hemoclot thrombin inhibitors (HTI), were also performed in order to
      detect any possible correlation between dabigatran plasma levels, its
      anticoagulant activity and the intensity of platelet dysfunction or fibrinolysis.
      RESULTS: A total of nineteen patients fulfilled our inclusion criteria (mean age
      62.3+/-7.2years; 47% males; median CHADS2-score: 3; interquartile range: 2-4). DE
      treatment was associated with a significant reduction of the lysis index (LI60)
      at 60min (p=0.036), and prolongation of the PFA-100 CEPI closure time (p=0.024).
      After dabigatran treatment, abnormal PFA-100 results were obtained in two
      patients (11%, 95% CI: 2%-33%). DE levels (determined by HTI) were strongly
      inversely correlated (rho=-0.85; p<0.001) with the area under the curve (AUC)
      values in ETP assay. Nuo association was found between HTI and PFA-100 CEPI CT
      (p=0.64), or LI60 measurements (p=0.60). CONCLUSIONS: Our findings indicate that
      DE might affect platelet function and fibrinolysis and highlight the potential
      role of ETP as an alternative option in DE monitoring. The intensity and clinical
      relevance of DE antiplatelet and fibrinolytic effects require further
      investigation.

PMID- 26219487
TI  - Burden of illness of rheumatoid arthritis in Latin America: a regional
      perspective.
AB  - Rheumatoid arthritis (RA) is one of the most important rheumatic diseases. Its
      prevalence varies among ethnic groups. Genetic and environmental factors
      influence its incidence and prevalence. This chronic disease will increase its
      frequency in the future due to population aging. The personal impact of this
      disease on many relevant areas of an individual requires special efforts to
      prevent and treat it properly. Adequate advice on several recently described risk
      factors such as tobacco and alcohol exposure, infections, obesity, and physical
      exercise should be part of every medical consultation. This knowledge should be
      incorporated to improve health care prevention programs. Patients and clinicians
      must work together through better communication skills to finally improve
      outcomes. Including RA in priority health care lists will need special effort
      from rheumatology societies and better communication with policy makers.

PMID- 26219488
TI  - Prognostic factors in a cohort of antisynthetase syndrome (ASS): serologic
      profile is associated with mortality in patients with interstitial lung disease
      (ILD).
AB  - The objectives of the present study were to compare the survival function of
      antisynthetase syndrome (ASS) Jo1-positive patients with ASS non-Jo1 patients,
      all with interstitial lung disease (ILD), and to evaluate other factors such as
      the extension of pulmonary disease and the time between the onset of symptoms and
      diagnosis and its association to survival in a cohort of ASS patients. Patients
      with ASS, all with ILD, were included. At the baseline, pulmonary function tests
      were realized and a high-resolution chest tomography was obtained; lung
      inflammation and fibrosis were measured with the Goh score and the Kazerooni
      index. The following autoantibodies were measured: Jo1, Ej, Oj, PL7, and PL12.
      Patients had to be positive for one of them in order to be included in the study.
      The survival function was estimated and compared with the log rank test, and the
      hazard ratio (HR) was estimated using Cox regression procedure. Forty-three
      patients were included, of which six patients died (14 %). Patients who died were
      different in comparison with survivors as regards the frequency of anti-Jo1
      positivity: Survivors had anti-Jo1 autoantibodies more frequently (86 %) than
      patients who died (50 %). The univariate Cox regression analysis identified four
      variables associated with survival: Jo1 status, arthritis, extent of ground
      glass, and consolidation (inflammation) in high-resolution computed tomography
      (HRCT) and baseline forced vital capacity. The serological status of patients
      (Jo1-positive vs non-Jo1), the extent of lung inflammation in the HRCT scan, a
      low forced vital capacity, and arthritis are associated with survival in ASS
      patients.

PMID- 26219490
TI  - Thrombotic events in patients with antiphospholipid syndrome treated with
      rivaroxaban: a series of eight cases.
AB  - The current treatment for antiphospholipid syndrome (APS) with thrombotic
      manifestation is long-term anticoagulation. Vitamin K antagonists (VKA) are
      usually the agents of choice. However, VKA limitations, such as unpredictable
      anticoagulation effects due to interaction with diet and other drugs, require
      regular monitoring. This may impact on patients' quality of life. Since the
      approval of new oral anticoagulants (NOAC) for non-valvular atrial fibrillation
      and deep vein thrombosis prevention, much has been speculated about its use in
      APS patients. We report here a series of eight APS patients with failure of
      thrombotic prevention during rivaroxaban use. All patients had venous thrombosis
      as the initial manifestation of APS, and two of them also had arterial
      manifestations. Three patients had triple antibody positivity. Five patients
      developed arterial events during the treatment with rivaroxaban. Until the
      results of ongoing trials of rivaroxaban for APS are presented, NOAC should not
      be recommended to APS patients. Our preliminary experience as well cases
      previously reported in the literature suggest that there is a high-risk group
      that is less protected with rivaroxaban, namely those with previous arterial
      thrombosis or triple positivity. VKA remains to be the mainstay treatment for
      thrombotic APS.

PMID- 26219489
TI  - Malignancies and anti-TNF therapy in rheumatoid arthritis: a single-center
      observational cohort study.
AB  - Inhibitors of tumor necrosing factor alpha (TNF-a) have proven to be highly
      effective in the treatment of rheumatoid arthritis (RA). Concerns, however, are
      raised about the possible association between these treatments and an increased
      development of malignancies. The objective of this paper was to compare the risk
      of hematologic and solid malignancies in patients treated for RA with anti-TNF
      therapy, with the risk in the general population. From January 2000 until January
      2012, all RA patients that started treatment with anti-TNF agents were included
      in this single-center cohort study. The primary outcome of this study was the
      incidence of malignancy after starting anti-TNF treatment. In our cohort of 365
      patients, 34 malignancies were discovered in 30 patients after the start of anti
      TNF treatment; 20 patients developed a solid malignancy, 6 a hematologic, 2 a
      solid and a hematologic malignancy, and 2 patients developed 2 solid
      malignancies. The overall incidence rate (IR) of malignancy was 1379.1 per
      100.000 patient years. The risk or standardized incidence ratio (SIR) of solid
      malignancy, calculated by comparison with the age-adjusted population in
      Flanders, was 120.1 in female and 136.7 in male patients. The calculated SIR of
      hematologic malignancy was 450.8 for women and 473.9 for men. Some immune
      modulation-related lymphoproliferative disorders regressed spontaneously when
      stopping TNF blockers. Overall, the malignancy risk in our rheumatoid arthritis
      patients treated with anti-TNF therapy was slightly higher than in the normal
      population; the risk of hematologic malignancies was more important. 

PMID- 26219491
TI  - Increased antibiotic release and equivalent biomechanics of a spacer cement
      without hard radio contrast agents.
AB  - We compared a novel calcium carbonate spacer cement (Copal(r) spacem) to well
      established bone cements. Electron microscopic structure and elution properties
      of the antibiotics ofloxacin, vancomycin, clindamycin, and gentamicin were
      examined. A knee wear simulator model for articulating cement spacers was
      established. Mechanical tests for bending strength, flexural modulus, and
      compressive and fatigue strength were performed. The electron microscopic
      analysis showed a microporous structure of the spacer cement, and this promoted a
      significantly higher and longer antibiotic elution. All spacer cement specimens
      released the antibiotics for a period of up to 50days with the exception of the
      vancomycin loading. The spacer cement showed significantly less wear scars and
      fulfilled the ISO 5833 requirements. The newly developed spacer cement is a
      hydrophilic antibiotic carrier with an increased release. Cement without hard
      radio contrast agents can improve tribological behaviour of spacers, and this may
      reduce reactive wear particles and abrasive bone defects. 

PMID- 26219492
TI  - Model-based clustering of Escherichia coli O157:H7 genotypes and their potential
      association with clinical outcome in human infections.
AB  - This study addresses the potential association of Escherichia coli O157:H7
      genetic clusters with severe clinical manifestations in humans. The genotypes
      used in this model-based clustering had been delineated on the basis of lineage
      specific polymorphism assay, Shiga toxin-encoding bacteriophage insertion site
      assay, clade typing, tir (A255T) polymorphism, variant analysis of Shiga toxin 2
      gene, and antiterminator Q genes. Based on this model, the distribution of
      genotypes among tested strains suggested the presence of 6 main genetic clusters
      of E. coli O157:H7 strains. Clusters 1 and 3 were observed to be more frequent
      among E. coli O157:H7 strains isolated from bloody diarrhea and hemolytic uremic
      syndrome, respectively. Consequently, our findings supported the growing evidence
      of the existence of distinct genotypes of E. coli O157:H7 that differ in their
      virulence levels to human. 

PMID- 26219493
TI  - Bird eyes distinguish summer from winter: Retinal response to acute photoperiod
      change in the night-migratory redheaded bunting.
AB  - Eyes are the part of the circadian timekeeping system but not involved in the
      photoperiod regulated seasonal physiology in songbirds. Here, two experiments
      tested whether eyes detect and respond to seasonal change in the photoperiod
      environment, by examining gene and protein expressions in the retinas of
      redheaded buntings exposed to a single long day (LD, 16L:8D), with controls on
      short days (SD, 8L:16D). In the first experiment, mRNA expression of genes
      implicated in the light perception (opsins, rhodopsin, neuropsin, melanopsin,
      peropsin) and photoperiod induction (eya3, tsh-beta, dio2, dio3) was measured at
      hours 15 and 19 (hour 0 = light on) on the first long day. There was a
      significant increase in the eya3, tsh-beta and dio2 mRNA expression, albeit with
      a temporal difference, and decrease in the neuropsin mRNA expression in buntings
      on the first long day. There was no change in the dio3, rhodopsin, melanopsin and
      peropsin mRNA expressions on exposure to long days. The second experiment
      immunohistochemically examined the eya3, tsh-beta and rhodopsin peptide
      expressions. eya3 was expressed in both light conditions, but with a significant
      higher levels in the retinal photoreceptor layer (PRL) under LD, as compared to
      SD. Similarly, tsh-beta was expressed in the PRL of LD retinas only. Rhodopsin
      levels were not significantly different between SD and LD conditions, however.
      These results for the first time show photoperiod-dependent molecular switches in
      the bunting retina, similar to the well documented thyroid hormone response genes
      based molecular cascades in the avian hypothalamus.

PMID- 26219494
TI  - Slowing the progression of Alzheimer's disease; what works?
AB  - Alzheimer's disease (AD) is an age-related progressive dementia, which is
      increasing in prevalence world-wide. Typically affecting short-term memory at
      onset, this devastating illness advances to impair all aspects of cognition, as
      well as non-cognitive domains. Although much effort has been made in recent years
      to develop disease-modifying treatments, medications which provided promising
      results in pre-clinical research have so far faltered in human clinical trials.
      Attention has recently shifted into trying to identify preventative measures that
      may delay the onset of the illness. Preventative factors include physical
      activity, proper diet, cognitive stimulation and the management of conditions
      such as hypertension, diabetes and obesity. However, it remains imperative to
      identify approaches that may help patients already diagnosed with the illness.
      Alongside pharmacological research, much work has been done on uncovering
      strategies which may slow down the progression of AD. This review aims to
      summarize evidence supporting or refuting methods impacting on the progression of
      the disease. AD remains a chronic and serious condition, therefore any
      intervention delaying the onset of moderate/severe symptoms will have a
      significant impact on patients and their families.

PMID- 26219495
TI  - Prevalence and Prognostic Impact of Valve Area-Gradient Patterns in Patients >=80
      Years With Moderate-to-Severe Aortic Stenosis (from the Prospective BELFRAIL
      Study).
AB  - Although degenerative aortic valve stenosis (AS) is common with increasing age,
      limited data exist regarding the prevalence and prognostic impact of its various
      valve area-gradient patterns in patients >=80 years. To test this,
      echocardiograms were obtained in 542 randomly selected subjects aged >=80 years
      recruited in the Belgium Cohort Study of the Very Elderly study (BFC80+).
      Subjects were divided into 3 groups: no or mild AS, moderate AS, and severe AS.
      Patients with severe AS were further stratified into those with high mean
      gradients (HG-AS) and those with paradoxically low mean gradients (LG-AS).
      Prevalence of moderate-to-severe AS was 14.7% and that of severe AS was 5.9%. In
      patients with severe AS, most (72%) exhibited paradoxical LG-AS. All patients
      with severe HG-AS were asymptomatic at the time of inclusion, whereas 48% of
      those with severe paradoxical LG-AS had significant symptoms. During follow-up,
      there were 2 aortic valve replacements and 230 deaths, of which 100 (43%) were of
      cardiovascular origin. Five-year overall survival rate was significantly worse in
      severe HG-AS than in any of the other groups (22 +/- 14% vs 62 +/- 2% in no or
      mild AS, 48 +/- 7% in moderate AS, and 43 +/- 10% in severe paradoxical LG-AS, p
      <0.01). Survival rate was similar among severe paradoxical LG-AS with and without
      low flow. In conclusion, in this large population-based sample of subjects >=80
      years, the prevalence of severe AS was 5.9%. Most of these subjects presented
      with the severe paradoxical LG-AS and a third of them were symptomatic. In this
      elderly community, severe HG-AS is a major determinant of prognosis, even in the
      absence of symptoms, whereas severe paradoxical LG-AS seems to behave similarly
      to moderate AS.

PMID- 26219496
TI  - Usefulness of Everolimus-Eluting Coronary Stent Implantation in Patients on
      Maintenance Hemodialysis.
AB  - The outcomes of second-generation drug-eluting stent (DES) are unknown in
      patients on maintenance hemodialysis (HD) although HD has been reported as a
      strong predictor of adverse outcome after the first-generation DES implantation.
      The OUCH-PRO Study is a prospective multicenter single-arm registry design to
      study clinical and angiographic outcomes after everolimus-eluting stent (EES).
      Patients who underwent maintenance HD were prospectively enrolled at the time of
      elective coronary intervention using EES. Quantitative coronary angiography was
      performed in an independent core laboratory. The primary end point was the
      occurrence of target vessel failure (TVF) defined as cardiac death, myocardial
      infarction (MI), and target vessel revascularization at 1 year. A total of 123
      patients were enrolled and 161 EES were implanted. The TVF rate at 1 year was 18%
      (4% cardiac death, 0% MI, 17% target vessel revascularization). No stent
      thrombosis was documented. Other clinical events at 1 year were 3% noncardiac
      death, 3% stroke, and 9% non-target-vessel revascularization. Late lumen loss in
      stent was 0.37 +/- 0.63 mm at 8 months. In conclusion, EES had a high TVF rate
      and great late lumen loss in patients on HD compared with previous huge EES data
      in non-HD patients.

PMID- 26219497
TI  - Role of IL-21 signaling pathway in transplant-related biology.
AB  - Since pro-inflammatory cytokine IL-21 and its receptor (IL-21R) are closely
      involved in regulating both innate and adaptive immune responses, it is
      conceivable that they may play important roles in the field of organ
      transplantation. IL-21/IL21-R regulates immune activities of CD8+ T cells, Tfh
      cells, Th17 cells, B cells, NK cells, dendritic cells and stimulates dendritic
      cells to produce high level of IL-6, TNF-alpha, and CCL2. However, their roles
      and underlying mechanisms remain obscure. Our present study is the first
      describing the role of IL-21 signaling pathway in transplant biology. It was
      found that IL-21/IL-21R signaling pathways contribute to the processes of
      ischemia/reperfusion and acute rejection of liver or kidney transplantation. IL
      21 is capable of regulating B cell function and immunoglobulin production,
      driving CD8+ T cell expansion, regulating Th17 and dendritic cell function.
      Deficiency of IL-21 may cause autoimmunity and infectious disease in clinical
      scenario patients. It is known that CD8+ T cells, Th17, and dendritic cells are
      closely involved in cardiac transplant tolerance. Our own original experimental
      research on mouse cardiac transplantation manifested that allograft survival
      could be significantly prolonged in the IL-21R deficient recipients. All these
      can deepen our understanding of immunobiological role of IL-21 and its receptor
      in the field of transplantation. Intervention of IL-21 signaling pathway may
      apparently regulate immunoresponses in vivo, which can be subsequently utilized
      as a therapeutic strategy in clinic. 

PMID- 26219498
TI  - Legionella suppresses the host unfolded protein response via multiple mechanisms.
AB  - The intracellular pathogen, Legionella pneumophila, secretes ~300 effector
      proteins to modulate the host environment. Given the intimate interaction between
      L. pneumophila and the endoplasmic reticulum, we investigated the role of the
      host unfolded protein response (UPR) during L. pneumophila infection.
      Interestingly, we show that the host identifies L. pneumophila infection as a
      form of endoplasmic reticulum stress and the sensor pATF6 is processed to
      generate pATF6(N), a transcriptional activator of downstream UPR genes. However,
      L. pneumophila is able to suppress the UPR and block the translation of
      prototypical UPR genes, BiP and CHOP. Furthermore, biochemical studies reveal
      that L. pneumophila uses two effectors (Lgt1 and Lgt2) to inhibit the splicing of
      XBP1u mRNA to spliced XBP1 (XBP1s), an UPR response regulator. Thus, we
      demonstrate that L. pneumophila is able to inhibit the UPR by multiple mechanisms
      including blocking XBP1u splicing and causing translational repression. This
      observation highlights the utility of L. pneumophila as a powerful tool for
      studying a critical protein homeostasis regulator. 

PMID- 26219499
TI  - The influence of salinity on the abundance, transcriptional activity, and
      diversity of AOA and AOB in an estuarine sediment: a microcosm study.
AB  - Estuarine sediment-seawater microcosms were established to evaluate the influence
      of salinity on the population, transcriptional activity, and diversity of ammonia
      oxidizing archaea (AOA) and bacteria (AOB). AOA was found to show the most
      abundant and the highest transcriptional activity under moderate salinity; on the
      other hand, AOB abundance was not sensitive to salinity variation but showed the
      highest transcriptional activity in the low-salinity microcosms. AOA exhibited
      more advantages than AOB on growth and ammonia-oxidizing activity under moderate-
      and high-salinity environments. The highest richness and diversity of active AOA
      were found under salinity of 15 psu. All the active AOA detected under the
      salinities studied were clustered into Nitrosopumilus maritimus linage, with the
      composition shifted from N. maritimus C12 cluster, N. maritimus like 1.1 cluster,
      N. maritimus SCM1 cluster, and N. maritimus like 1.2 cluster to N. maritimus C12
      and N. maritimus A10 clusters when salinity was increased from 5 to 30 psu. 

PMID- 26219500
TI  - Replacement of pr gene with Japanese encephalitis virus pr using reverse genetics
      reduces antibody-dependent enhancement of dengue virus 2 infection.
AB  - Severe dengue is more likely found during secondary heterologous dengue virus
      (DENV) infection or primary infection of infants born to dengue-immune mothers
      and led to the hypothesis of antibody-dependent enhancement (ADE). It has been
      reported that pre-membrane (prM)-reactive antibodies do not efficiently
      neutralize DENV infection but instead potently promote ADE infection. Meanwhile,
      these enhancing anti-prM antibodies mainly react with the precursor (pr) peptide.
      To evaluate the effect of pr gene substitution on neutralization and ADE of DENV
      infection, a novel chimeric dengue virus (JEVpr/DENV2) was rationally constructed
      by replacing the DENV pr gene with Japanese encephalitis virus (JEV) pr gene,
      based on the full-length infectious complementary DNA (cDNA) clone of DENV2
      ZS01/01. We found that chimeric JEVpr/DENV2 showed reduced virulence and good
      immunogenicity. In addition, anti-JEVpr/DENV2 sera showed broad cross-reactivity
      and efficient neutralizing activity with all four DENV serotypes and immature
      DENV2 (ImDENV2). Most importantly, compared with anti-DENV2 sera, anti
      JEVpr/DENV2 sera showed significantly reduced enhancing activity of DENV
      infection in K562 cells. These results suggest that the ADE activities could be
      reduced by replacing the DENV pr gene with JEV pr gene. These findings may help
      us better understand the pathogenesis of DENV infection and provide a reference
      for the development of a vaccine against DENV.

PMID- 26219502
TI  - Phenolic compounds from the fungus Inonotus obliquus and their antioxidant
      properties.

PMID- 26219503
TI  - World Diabetes Congress Vancouver 2015: Public Health and Epidemiology Stream.

PMID- 26219501
TI  - Heparin and related polysaccharides: synthesis using recombinant enzymes and
      metabolic engineering.
AB  - Glycosaminoglycans are linear anionic polysaccharides that exhibit a number of
      important biological and pharmacological activities. The two most prominent
      members of this class of polysaccharides are heparin/heparan sulfate and the
      chondroitin sulfates (including dermatan sulfate). These polysaccharides, having
      complex structures and polydispersity, are biosynthesized in the Golgi of most
      animal cells. The chemical synthesis of these glycosaminoglycans is precluded by
      their structural complexity. Today, we depend on food animal tissues for their
      isolation and commercial production. Ton quantities of these glycosaminoglycans
      are used annually as pharmaceuticals and nutraceuticals. The variability of
      animal-sourced glycosaminoglycans, their inherent impurities, the limited
      availability of source tissues, the poor control of these source materials, and
      their manufacturing processes suggest a need for new approaches for their
      production. Over the past decade, there have been major efforts in the
      biotechnological production of these glycosaminoglycans. This mini-review focuses
      on the use of recombinant enzymes and metabolic engineering for the production of
      heparin and chondroitin sulfates. 

PMID- 26219504
TI  - Hexachlorobenzene induces cell proliferation, and aryl hydrocarbon receptor
      expression (AhR) in rat liver preneoplastic foci, and in the human hepatoma cell
      line HepG2. AhR is a mediator of ERK1/2 signaling, and cell cycle regulation in
      HCB-treated HepG2 cells.
AB  - Hexachlorobenzene (HCB) is a widespread environmental pollutant, and a liver
      tumor promoter in rodents. Depending on the particular cell lines studied,
      exposure to these compounds may lead to cell proliferation, terminal
      differentiation, or apoptosis. The aryl hydrocarbon receptor (AhR) is a ligand
      activated transcription factor that is involved in drug and xenobiotic
      metabolism. AhR can also modulate a variety of cellular and physiological
      processes that can affect cell proliferation and cell fate determination. The
      mechanisms by which AhR ligands, both exogenous and endogenous, affect these
      processes involve multiple interactions between AhR and other signaling pathways.
      In the present study, we examined the effect of HCB on cell proliferation and AhR
      expression, using an initiation-promotion hepatocarcinogenesis protocol in rat
      liver and in the human-derived hepatoma cell line, HepG2. Female Wistar rats were
      initiated with a single dose of 100 mg/kg of diethylnitrosamine (DEN) at the
      start of the experiment. Two weeks later, daily dosing of 100 mg/kg HCB was
      maintained for 10 weeks. Partial hepatectomy was performed 3 weeks after
      initiation. The number and area of glutathione S-transferase-P (GST-P)-positive
      foci, in the rat liver were used as biomarkers of liver precancerous lesions.
      Immunohistochemical staining showed an increase in proliferating cell nuclear
      antigen (PCNA)-positive cells, along with enhanced AhR protein expression in
      hepatocytes within GST-P-positive foci of (DEN HCB) group, when compared to DEN.
      In a similar manner, Western blot analysis demonstrated that HCB induced PCNA and
      AhR protein expression in HepG2 cells. Flow cytometry assay indicated that the
      cells were accumulated at S and G2/M phases of the cell cycle. HCB increased
      cyclin D1 protein levels and ERK1/2 phosphorylation in a dose-dependent manner.
      Treatment of cells with a selective MEK1 inhibitor, prevented HCB-stimulatory
      effect on PCNA and cyclinD1, indicating that these effects are mediated by
      ERK1/2. Pretreatment with an AhR antagonist, prevented HCB-induced PCNA protein
      levels, ERK1/2 phosphorylation and alterations in cell cycle distribution. These
      results demonstrate that HCB-induced HepG2 proliferation and cell cycle
      progression depend on ERK1/2 phosphorylation which is mediated by the AhR. Our
      results provide a clue to the molecular events involved in the mechanism of
      action of HCB-induced hepatocarcinogenesis.

PMID- 26219505
TI  - Triptolide disrupts fatty acids and peroxisome proliferator-activated receptor
      (PPAR) levels in male mice testes followed by testicular injury: A GC-MS based
      metabolomics study.
AB  - Triptolide is the major active ingredient of Tripterygium Glycosides (TG), a
      traditional Chinese medicine with very potent anti-inflammatory effects and has
      been used in China for the treatment of rheumatoid arthritis and many other
      inflammatory diseases. However, clinical application of triptolide is restricted
      due to its multiple side effects, especially male infertility. The mechanism of
      triptolide on reproduction toxicity remains unclear. In the present study, a GC
      MS based metabolomic approach was employed to evaluate the mechanism of
      triptolide-induced reproductive toxicity as well as identify potential novel
      biomarkers for the early detection of spermatogenesis dysfunction. In brief, male
      mice were divided into two groups with or without triptolide intraperitoneal
      injection at 60 MUg/kg/day for 2 weeks and toxic effect of triptolide on
      testicular tissues were examined by biochemical indicator analysis, testis
      histopathologic analysis, and sperm quantity analysis. Metabolomics technology
      was then performed to evaluate systematically the endogenous metabolites
      profiling. Our results demonstrated that triptolide suppressed the marker-enzymes
      of spermatogenesis and testosterone levels, decreased sperm counts, reduced the
      gonad index and destroyed the microstructure of testis. Multivariate data
      analysis revealed that mice with triptolide induced testicular toxicity could be
      distinctively differentiated from normal animals and 35 and 39 small molecule
      metabolites were changed significantly in testis and serum, respectively (Fold
      changes >1.5, P<0.05), in triptolide-treated mice. Abnormal level of fatty acids,
      an important energy source of sertoli cells with critical role in maintaining
      normal function of the testis tissue, was observed in triptolide-treated mice.
      Additionally, the protein expressions of PPAR, a transcription factor known to
      play a pivotal role in lipid and energy metabolism was significantly decreased in
      the testis tissue of triptolide-treated mice. In summary, our study represents
      the first comprehensive GC-MS based metabolomics analysis of triptolide-induced
      testicular toxicity. We reported for the first time that exposure to triptolide
      led to marked changes of a panel of endogenous metabolites in both testis and
      serum. The impairment of spermatogenesis may be caused by abnormal lipid and
      energy metabolism in testis via the down-regulation of PPARs mediated by
      triptolide. The presence of research suggested that PPARs and its related fatty
      acids metabolism may serve as potential targets for intervention or treatment of
      male infertility induced by triptolide.

PMID- 26219506
TI  - Impaired mitochondrial function in HepG2 cells treated with hydroxy-cobalamin[c
      lactam]: A cell model for idiosyncratic toxicity.
AB  - The vitamin B12 analog hydroxy-cobalamin[c-lactam] (HCCL) impairs mitochondrial
      protein synthesis and the function of the electron transport chain. Our goal was
      to establish an in vitro model for mitochondrial dysfunction in human hepatoma
      cells (HepG2), which can be used to investigate hepatotoxicity of idiosyncratic
      mitochondrial toxicants. For that, HepG2 cells were treated with HCCL, which
      inhibits the function of methylmalonyl-CoA mutase and impairs mitochondrial
      protein synthesis. Secondary, cells were incubated with propionate that served as
      source of propionyl-CoA, a percursor of methylmalonyl-CoA. Dose-finding
      experiments were conducted to evaluate the optimal dose and treatment time of
      HCCL and propionate for experiments on mitochondrial function. 50 MUM HCCL was
      cytotoxic after exposure of HepG2 cells for 2d and 10 and 50 MUM HCCL enhanced
      the cytotoxicity of 100 or 1000 MUM propionate. Co-treatment with HCCL (10 MUM)
      and propionate (1000 MUM) dissipated the mitochondrial membrane potential and
      impaired the activity of enzyme complex IV of the electron transport chain.
      Treatment with HCCL decreased the mRNA content of mitochondrially encoded
      proteins, whereas the mtDNA content remained unchanged. We observed mitochondrial
      ROS accumulation and decreased mitochondrial SOD2 expression. Moreover, electron
      microscopy showed mitochondrial swelling. Finally, HepG2 cells pretreated with a
      non-cytotoxic combination of HCCL (10 MUM) and propionate (100 MUM) were more
      sensitive to the mitochondrial toxicants dronedarone, benzbromarone, and
      ketoconazole than untreated cells. In conclusion, we established and
      characterized a cell model, which could be used for testing drugs with
      idiosyncratic mitochondrial toxicity.

PMID- 26219507
TI  - Di (2-ethylhexyl) phthalate exposure during pregnancy disturbs temporal sex
      determination regulation in mice offspring.
AB  - Animal researches and clinical studies have supported the relevance between
      phthalates exposure and testicular dysgenesis syndrome (TDS). These disorders may
      comprise common origin in fetal life, especially during sex determination and
      differentiation, where the mechanism remains unclear. The present study evaluated
      the disturbances in gene regulatory networks of sex determination in fetal mouse
      by in utero Di (2-ethylhexyl) phthalate (DEHP) exposure. Temporal expression of
      key sex determination genes were examined during the critical narrow time window,
      using whole-mount in situ hybridization and quantitative-PCR. DEHP exposure
      resulted in significant reduction in mRNA of Sry during sex determination from
      gestation day (GD) 11.0 to 11.5 in male fetal mice, and the increasing of Sry
      expression to threshold level on GD 11.5 was delayed. Meanwhile, Gadd45g and
      Gata4, the upstream genes of Sry, and downstream gene Sox9 were also
      significantly downregulated in expression. In fetal females, the expression of
      Wnt4 and beta-catenin were up-regulated by DEHP exposure. Taken together, the
      results suggest that the potential mechanism of gonadal development disorder by
      DEHP may origin from repression of important male sex determination signaling
      pathway, involving Gadd45g -> Gata4 -> Sry -> Sox9. The results would promote a
      better understanding of the association between phthalate esters (PAEs) exposure
      and the reductive disorder.

PMID- 26219509
TI  - [Sensory and autonomic neuropathies and pain-related channelopathies].
AB  - Loss of pain perception can result from neurodevelopmental defects, degeneration
      of nociceptive fibers, or altered excitability of sensory neurons. Hereditary
      neurodegeneration leading to pain loss is classified as sensory and autonomic
      neuropathy (HSAN). Mutations in approximately 15 genes have been identified in
      the group of HSAN disorders. Hallmark of the disease is a liability to injury
      because of impaired acute pain as a warning system to prevent harm. The
      clinically overlapping "congenital insensitivity to pain (CIP)" is caused by
      mutations in voltage-gated sodium channels, which control the excitability of
      nociceptors. However, mutations in the latter genes can also result in disorders
      with increased pain susceptibility. This review summarizes the clinical
      presentation of HSAN and pain-related channelopathies and discusses the
      underlying disease mechanisms. 

PMID- 26219508
TI  - beta2-Adrenergic signal transduction plays a detrimental role in subchondral bone
      loss of temporomandibular joint in osteoarthritis.
AB  - The present study tested whether activation of the sympathetic tone by aberrant
      joint loading elicits abnormal subchondral bone remodeling in temporomandibular
      joint (TMJ) osteoarthritis. Abnormal dental occlusion was created in experimental
      rats, which were then intraperitoneally injected by saline, propranolol or
      isoproterenol. The norepinephrine contents, distribution of sympathetic nerve
      fibers, expression of beta-adrenergic receptors (beta-ARs) and remodeling
      parameters in the condylar subchondral bone were investigated. Mesenchymal stem
      cells (MSCs) from condylar subchondral bones were harvested for comparison of
      their beta-ARs, pro-osteoclastic gene expressions and pro-osteoclastic function.
      Increases in norepinephrine level, sympathetic nerve fiber distribution and beta2
      AR expression were observed in the condylar subchondral bone of experimental
      rats, together with subchondral bone loss and increased osteoclast activity. beta
      antagonist (propranolol) suppressed subchondral bone loss and osteoclast
      hyperfunction while beta-agonist (isoproterenol) exacerbated those responses.
      MSCs from experimental condylar subchondral bone expressed higher levels of beta2
      AR and RANKL; norepinephrine stimulation further increased their RANKL expression
      and pro-osteoclastic function. These effects were blocked by inhibition of beta2
      AR or the PKA pathway. RANKL expression by MSCs decreased after propranolol
      administration and increased after isoproterenol administration. It is concluded
      that beta2-AR signal-mediated subchondral bone loss in TMJ osteoarthritisis
      associated with increased RANKL secretion by MSCs. 

PMID- 26219510
TI  - Asymmetric synthesis of H1 receptor antagonist (R,R)-clemastine.
AB  - The first asymmetric synthesis of (R,R)-clemastine (1) has been accomplished by
      the coupling of (R)-tertiary alcohol 2 and (R)-chloroethylpyrrolidine 3 via O
      alkylation. (R)-Tertiary alcohol 2 was synthesized by stereoselective alkylation
      of chiral alpha-benzyloxy ketone with Grignard reagent via chelation-controlled
      1,4-asymmetric induction. In the reaction, chiral benzyl group acts as a chiral
      auxiliary as well as a protecting group. (R)-Chloroethylpyrrolidine 3 was
      prepared by asymmetric transformation starting with L-homoserine lactone, in
      which racemization-minimized N-allylation and ring-closing metathesis were
      involved as key steps. 

PMID- 26219511
TI  - Physical restraint: experiences, attitudes and opinions of adult intensive care
      unit nurses.
AB  - BACKGROUND: Patients within the adult intensive care unit have the potential to
      develop delirium and agitation. This can result in the patient displaying
      unwanted behaviours such as attempting to remove the medical devices to which
      they are attached. Some adult intensive care units within the UK are starting to
      adopt physical restraint as a method of managing unwanted behaviours. AIM: To
      determine the experiences, attitudes and opinions of adult intensive care nurses
      in relation to the application of physical restraint. DESIGN: Questionnaire
      survey. METHODS: A postal questionnaire was distributed to all nurses (n = 192)
      within two purposefully selected large adult intensive care units in the UK.
      RESULTS: Data were collected between November 2012 and February 2013. The
      questionnaire was completed by 38.9% (n = 75) of the nurses contacted. All
      believed that physical restraint had a place, with the majority of the view that
      the reason for its application was to maintain patient safety. Some expressed
      discomfort about the use of physical restraint. Nurses were happy to discuss the
      use of restraint with families. There was a perceived need for training and
      support for nursing staff as well as the need for medical staff to support the
      decision-making process. CONCLUSION: Nurses require more support and evidence to
      base their decision-making upon. They require guidance from professional bodies
      as well as support from medical colleagues. The findings have limited
      generalizability as they can only be applied to the units accessed and the
      response rate was poor. RELEVANCE TO CLINICAL PRACTICE: Alternative approaches
      such as pain management, sleep promotion and the involvement of relatives need to
      be explored before physical restraint policy can be written. Further research is
      required into the safety of physical restraint, alternative methods of managing
      the risk of agitation and identifying predisposing factors to accidental device
      removal.

PMID- 26219512
TI  - A Case Controlled Examination of the Interpersonal Theory of Suicide in the
      Second Half of Life.
AB  - The interpersonal theory of suicide proposes that the most proximal cause of
      suicide is the combination of thwarted belongingness and perceived burdensomeness
      coupled with a pre-existing vulnerability of reduced fear of death and increased
      pain tolerance. This pre-existing vulnerability develops in response to painful
      and provocative life events. According to the theory, empirically demonstrated
      risk factors for suicide operate by increasing the likelihood of one or more of
      the theory's constructs. The current study examined the relations of the major
      constructs of the interpersonal theory with suicide case status compared to
      living controls in the second half of life. The current study used a pre-existing
      psychological autopsy database to compare suicide decedents to living controls 50
      years and older. Theory constructs were measured by composite scores of thwarted
      belongingness, perceived burdensomeness, and painful and provocative experiences
      using an a priori selection of items comprising each construct. Suicide decedents
      experienced greater levels of all three of the theory's constructs when examined
      independently compared to living controls. When examined simultaneously while
      also controlling for Major Depression, greater perceived burdensomeness and
      painful and provocative experiences were associated with suicide case status (vs.
      control). The interpersonal theory is a comprehensive framework that may be
      useful in understanding risk for death by suicide in the second half of life.
      Clinical management of suicide risk for adults in the second half of life could
      include a focus on perceived burdensomeness, as the IPTS proposes that this
      psychological state is amenable to change via therapeutic intervention.

PMID- 26219513
TI  - Antigenic variation of the human influenza A (H3N2) virus during the 2014-2015
      winter season.
AB  - The human influenza A (H3N2) virus dominated the 2014-2015 winter season in many
      countries and caused massive morbidity and mortality because of its antigenic
      variation. So far, very little is known about the antigenic patterns of the
      recent H3N2 virus. By systematically mapping the antigenic relationships of H3N2
      strains isolated since 2010, we discovered that two groups with obvious antigenic
      divergence, named SW13 (A/Switzerland/9715293/2013-like strains) and HK14 (A/Hong
      Kong/5738/2014-like strains), co-circulated during the 2014-2015 winter season.
      HK14 group co-circulated with SW13 in Europe and the United States during this
      season, while there were few strains of HK14 in mainland China, where SW13 has
      dominated since 2012. Furthermore, we found that substitutions near the receptor
      binding site on hemagglutinin played an important role in the antigenic variation
      of both the groups. These findings provide a comprehensive understanding of the
      recent antigenic evolution of H3N2 virus and will aid in the selection of vaccine
      strains. 

PMID- 26219514
TI  - Differences between intrinsic and extrinsic ureteropelvic junction obstruction
      related to crossing vessels: histology and functional analyses.
AB  - PURPOSE: In children, ureteropelvic junction obstruction (UPJO) is mostly caused
      by intrinsic factors (IUPJO); extrinsic UPJO are rare and often due to crossing
      vessels (CVs). METHODS: We retrospectively reviewed all data of children with
      UPJO that underwent surgery in our institution from 2004 to 2011. Analyses
      included age at surgery, gender, preoperative and postoperative results of
      ultrasound and renal scans [differential renal function (DRF); signs of
      obstruction], and pathology reports. Available histological specimens of cases
      with CV were compared to a random selection of intrinsic cases in a blinded
      fashion. After additional Masson's trichrome staining, the specimens were scored
      for fibrosis, muscular hypertrophy, and chronic inflammation. RESULTS: Out of 139
      patients with UPJO, 39 cases were associated with CV. Median age at surgery was
      68 months (range 2-194) in the CV group and 11.5 months (range 0-188) in IUPJO
      group. Laparoscopic dismembered pyeloplasty (LDMP) was carried out in 134 and
      open DMP in five patients. Preoperative ultrasound identified 28/39 cases with
      CV. DRF below 40 % was more frequently seen in CV patients (p = 0.020).
      Histological analyses revealed no differences between the CV and IUPJO specimens
      in total. CV patients with higher grades of muscular hypertrophy had lower
      preoperative DRF, compared to those with higher preoperative DRF (p = 0.026).
      Functional recovery after (L)DMP was excellent in both groups. CONCLUSION: We
      could not find any significant histological differences between CV and IUPJO in
      children. To obtain excellent functional recovery, surgical procedures with a
      definite correction of the UPJ should be preferred in paediatric patients with
      CV.

PMID- 26219515
TI  - European postgraduate training in geriatric medicine: data of a systematic
      international survey.
AB  - INTRODUCTION: High-quality education and training standards in geriatric medicine
      are important to develop the profession of geriatric medicine. The objective of
      the study was to give a structured update on postgraduate specialty training in
      geriatric medicine throughout Europe to assess the need for further developments
      in postgraduate education. METHODS: The study was performed as a cross-sectional
      structured quantitative online survey with qualitative comments. The survey
      content covered organization, content and educational aspects of specialty
      training in geriatric medicine in European countries. After piloting, the
      questionnaire was sent to experts in geriatric medicine with a special interest
      in postgraduate training who are members of one of the following organizations;
      European Union of Medical Specialists (UEMS), European Academy for the Medicine
      of Aging (EAMA), and European Union Geriatric Medicine Society (EUGMS). RESULTS:
      Respondents to the survey represented 31 European countries. Geriatric medicine
      is recognized as an independent postgraduate specialty in 61.3 % (19/31) and as a
      subspecialty in 29.0 % (9/31) of the countries. In 5 of the 31 countries
      geriatric medicine is not recognized at all. Nearly all countries offering
      postgraduate training in geriatric medicine have written, competence-based
      curricula covering different learning domains. 20/31 countries (64.5 %) have some
      kind of specialist assessment. DISCUSSION: The survey tries to give an actual
      condensed picture of postgraduate specialty training in geriatric medicine across
      Europe. Results show a consistent improvement in the recognition of geriatric
      medicine as independent specialty over the last decade. Continuous development of
      specialty training in geriatric medicine is required to medical address the
      public health needs of an aging population. Competence-based educational models
      including adequate forms of assessment should be targeted throughout Europe. To
      emphasize the importance of postgraduate geriatric training, it should be a
      mission to harmonize training standards across Europe.

PMID- 26219516
TI  - MERA: a webserver for evaluating backbone torsion angle distributions in dynamic
      and disordered proteins from NMR data.
AB  - MERA (Maximum Entropy Ramachandran map Analysis from NMR data) is a new webserver
      that generates residue-by-residue Ramachandran map distributions for disordered
      proteins or disordered regions in proteins on the basis of experimental NMR
      parameters. As input data, the program currently utilizes up to 12 different
      parameters. These include three different types of short-range NOEs, three types
      of backbone chemical shifts ((15)N, (13)C(alpha), and (13)C'), six types of J
      couplings ((3)JHNHalpha, (3)JC'C', (3)JC'Halpha, (1)JHalphaCalpha, (2)JCalphaN
      and (1)JCalphaN), as well as the (15)N-relaxation derived J(0) spectral density.
      The Ramachandran map distributions are reported in terms of populations of their
      15 degrees  * 15 degrees  voxels, and an adjustable maximum entropy weight factor
      is available to ensure that the obtained distributions will not deviate more from
      a newly derived coil library distribution than required to account for the
      experimental data. MERA output includes the agreement between each input
      parameter and its distribution-derived value. As an application, we demonstrate
      performance of the program for several residues in the intrinsically disordered
      protein alpha-synuclein, as well as for several static and dynamic residues in
      the folded protein GB3. 

PMID- 26219517
TI  - Dynamic nuclear polarization of nucleic acid with endogenously bound manganese.
AB  - We report the direct dynamic nuclear polarization (DNP) of (13)C nuclei of a
      uniformly [(13)C,(15)N]-labeled, paramagnetic full-length hammerhead ribozyme
      (HHRz) complex with Mn(2+) where the enhanced polarization is fully provided by
      the endogenously bound metal ion and no exogenous polarizing agent is added. A
      (13)C enhancement factor of epsilon = 8 was observed by intra-complex DNP at 9.4
      T. In contrast, "conventional" indirect and direct DNP experiments were performed
      using AMUPol as polarizing agent where we obtained a (1)H enhancement factor of
      epsilon ~ 250. Comparison with the diamagnetic (Mg(2+)) HHRz complex shows that
      the presence of Mn(2+) only marginally influences the (DNP-enhanced) NMR
      properties of the RNA. Furthermore two-dimensional correlation spectra ((15)N
      (13)C and (13)C-(13)C) reveal structural inhomogeneity in the frozen, amorphous
      state indicating the coexistence of several conformational states. These
      demonstrations of intra-complex DNP using an endogenous metal ion as well as DNP
      enhanced MAS NMR of RNA in general yield important information for the
      development of new methods in structural biology. 

PMID- 26219518
TI  - Glioma homing peptide-modified PEG-PCL nanoparticles for enhanced anti-glioma
      therapy.
AB  - BACKGROUND: Peptide-mediated drug delivery system (DDS) has been increasingly
      used to promote on-demand treatment efficacy of cancers. Herein, LTLRWVGLMS
      (LS10) peptide is selected as the functional ligand for specific glioma-targeting
      drug delivery. LS10 peptide selectively binds to NG2 proteins that are widely
      overexpressed in the glioma cells and restricted in normal tissue. LS10 peptide
      decorated DDS is expected to hold vast promises in glioma therapy and decrease
      unwanted side effects. METHODS: LS10 peptide was conjugated on the surface of
      poly(ethylene glycol)-poly(E-caprolactone) (PEG-PCL) nanoparticles via 1-ethyl-3
      (3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysulfosuccinimide
      coupling reaction. Using U87MG cells as the glioma cell model, cellular uptake,
      internalization mechanism, cellular cytotoxicity and apoptosis were investigated.
      1,1'-Dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine iodide were used as
      fluorescence probes to investigated in vivo glioma targeting capability of LS10
      NP. The glioma therapeutic efficacy of paclitaxel-loaded LS10-NP was studied on
      glioma-bearing nude mice. RESULTS: The LS10-NP with size of 119 nm enhanced
      cellular uptake on U87MG cells, increased cytotoxicity of the loaded paclitaxel
      (PTX), and improved penetration in 3D U87MG glioma spheres. In vivo
      biodistribution experiments showed that LS10-NP exhibited the enhanced drug
      localization at glioma site, which resulted in prolonged survival time of glioma
      bearing mice. CONCLUSION: Our results indicated that LS10 peptide-modified
      nanoparticulate DDS could significantly improve the anti-glioma efficacy.

PMID- 26219519
TI  - Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system
      for potential brain targeting.
AB  - BACKGROUND: Delivery of drugs to brain is a subtle task in the therapy of many
      severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the
      blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand
      conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf)
      conjugated SLN system is first time attempted for effective brain targeting in
      this study. PURPOSE: Preparation of Lf-modified docetaxel (DTX)-loaded SLN for
      proficient delivery of DTX to brain. METHODS: DTX-loaded SLN were prepared using
      emulsification and solvent evaporation method and conjugation of Lf on SLN
      surface (C-SLN) was attained through carbodiimide chemistry. These lipidic
      nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro
      release studies. Colloidal stability study was performed in biologically
      simulated environment (normal saline and serum). These lipidic nanoparticles were
      further evaluated for its targeting mechanism for uptake in brain tumour cells
      and brain via receptor saturation studies and distribution studies in brain,
      respectively. RESULTS: Particle size of lipidic nanoparticles was found to be
      optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR)
      confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed
      augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was
      demonstrated by receptor saturation and uptake studies. Brain concentration of
      DTX was elevated significantly with C-SLN than marketed formulation. CONCLUSIONS:
      It is evident from the cytotoxicity, uptake that SLN has potential to deliver
      drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN)
      further increased the targeting potential for brain tumour. Moreover, brain
      distribution studies corroborated the use of C-SLN as a viable vehicle to target
      drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery
      system to brain as it possessed remarkable biocompatibility, stability and
      efficacy than other reported delivery systems.

PMID- 26219521
TI  - Newly Graduated Nurses' Competence and Individual and Organizational Factors: A
      Multivariate Analysis.
AB  - OBJECTIVE: To study the relationships between newly graduated nurses' (NGNs')
      perceptions of their professional competence, and individual and organizational
      work-related factors. METHODS: A multivariate, quantitative, descriptive,
      correlation design was applied. Data collection took place in November 2012 with
      a national convenience sample of 318 NGNs representing all main healthcare
      settings in Finland. Five instruments measured NGNs' perceptions of their
      professional competence, occupational commitment, empowerment, practice
      environment, and its ethical climate, with additional questions on turnover
      intentions, job satisfaction, and demographics. Descriptive statistics summarized
      the demographic data, and inferential statistics multivariate path analysis
      modeling estimated the relationships between the variables. RESULTS: The
      strongest relationship was found between professional competence and empowerment,
      competence explaining 20% of the variance of empowerment. The explanatory power
      of competence regarding practice environment, ethical climate of the work unit,
      and occupational commitment, and competence's associations with turnover
      intentions, job satisfaction, and age, were statistically significant but
      considerably weaker. Higher competence and satisfaction with quality of care were
      associated with more positive perceptions of practice environment and its ethical
      climate as well as higher empowerment and occupational commitment. CONCLUSIONS:
      Apart from its association with empowerment, competence seems to be a rather
      independent factor in relation to the measured work-related factors. Further
      exploration would deepen the knowledge of this relationship, providing support
      for planning educational and developmental programs. Research on other individual
      and organizational factors is warranted to shed light on factors associated with
      professional competence in providing high-quality and safe care as well as
      retaining new nurses in the workforce. CLINICAL RELEVANCE: The study sheds light
      on the strength and direction of the significantly associated work-related
      factors. Nursing professional bodies, managers, and supervisors can use the
      findings in planning orientation programs and other occupational interventions
      for NGNs.

PMID- 26219520
TI  - Metabolic Uncoupling Following Cardiopulmonary Bypass.
AB  - OBJECTIVE: The objective of this study was to characterize the natural history of
      metabolic uncoupling (type B hyperlactemia and hyperglycemia) following
      cardiopulmonary bypass (CPB), and to determine the impact of insulin therapy on
      time to lactate normalization in patients without low cardiac output. DESIGN: The
      design used was a retrospective cohort study. SETTING: The study was set in a
      pediatric cardiac intensive care unit in a tertiary-care urban children's
      hospital. PATIENTS: All patients were aged <=21 years admitted between 2007 and
      2013 following cardiac surgery involving CPB with empiric intraoperative
      corticosteroids. ELIGIBILITY CRITERIA: simultaneous hyperlactemia (>=3.5 mEq/L)
      and hyperglycemia (>=200 mg/dL) within 48 hours after bypass. EXCLUSION CRITERIA:
      Exclusion criteria were evidence of low cardiac output state, diabetes or
      postoperative steroid administration. INTERVENTIONS: Characteristics were
      compared between those treated with insulin and those who were not (controls).
      OUTCOME MEASURES: Outcome measures used were time from admission to onset of
      hyperglycemia and hyperlactemia and time to resolution. Clinical outcomes
      included duration of mechanical ventilation, length of stay, unplanned
      readmission/reoperation, hypoglycemia and death. RESULTS: Of the 1345 patients
      receiving CPB, 132 (9.8%) met inclusion criteria. Seventy-eight (59%) were
      treated with insulin, leaving 54 controls. Patient characteristics, surgical
      complexity and time to onset of hyperglycemia and hyperlactemia were similar
      between groups. The insulin group had a shorter duration of hyperglycemia. There
      was no significant difference between groups in time to lactate normalization,
      ventilator days, length of stay, readmission and reoperation rates. Hypoglycemia
      (<60 mg/dL) occurred in three patients. CONCLUSIONS: In children with metabolic
      uncoupling after CPB, insulin use did not shorten the time to lactate
      normalization or alter clinical outcomes. These findings suggest that type B
      hyperlactemia with hyperglycemia after CPB will resolve spontaneously and does
      not warrant specific treatment.

PMID- 26219522
TI  - [Obliteration of mastoid cavities: 30 years of experience with recommendations
      for surgical strategy].
AB  - BACKGROUND: The obliteration of mastoid cavities is an appropriate intervention
      to sustainably improve patients' quality of life. MATERIALS AND METHODS: After 30
      years, 843 cases of mastoid obliteration were analyzed from the pool of data
      resulting from 16,000 surgical procedures on the ear. The materials used by the
      authors included cartilage/bone, Palva flaps, and bone pate; as well as
      alloplastic material such as hydroxyapatite (HA) and bioactive glass granules
      (BAG S53P4) from BonAlive(r) (BonAlive Biomaterials Ltd., Turku, Finland).
      Pathological findings included rejection with inflammation, granulation of the
      auditory canal reconstruction, unclear retraction pockets, as well as shrinkage
      and cicatricial contraction. The follow-up interval was at least 4 months, with
      an average of 33 months (standard deviation +/- 27.8 months). RESULTS: Use of HA
      was discontinued after 18 cases, because rejection and retraction occurred in 33%
      of patients. The same applied for bone pate after 33 cases, with a pathological
      finding in 21%. The Palva flaps (145 cases) showed pathological findings in 21%
      of cases, primarily in the form of shrinkage (7%) and retractions (10%).
      Cartilage/bone pieces (516 cases) and BAG S53P4 (133 cases) only showed abnormal
      postoperative findings in 8% and 3%, respectively. It is recommended to focus
      particularly on auditory canal and canal entrance expansion during mastoid
      obliteration surgery. When using the bioactive glass granules, postoperative use
      of a mini-drain for 1-2 days is beneficial, in order to avoid accumulation of
      seroma fluid in the mastoid. CONCLUSION: In our experience, a combination of BAG
      S53P4 and cartilage as cover is a suitable material for cavity obliteration.

PMID- 26219524
TI  - [Inpatient rehabilitation of adult CI users: Results in dependency of duration of
      deafness, CI experience and age].
AB  - BACKGROUND: Cochlear implants (CI) have proven to be a highly effective treatment
      for severe hearing loss or deafness. Inpatient rehabilitation therapy is
      frequently discussed as a means to increase the speech perception abilities
      achieved by CI. However, thus far there exists no quantitative evaluation of the
      effect of these therapies. METHODS: A retrospective analysis of audiometric data
      obtained from 1355 CI users compared standardized and qualitative speech
      intelligibility tests conducted at two time points (admission to and discharge
      from inpatient hearing therapy, duration 3-5 weeks). The test battery comprised
      examination of vowel/consonant identification, the Freiburg numbers and
      monosyllabic test (65 and 80 dB sound pressure level, SPL, free-field sound
      level), the Hochmair-Schulz-Moser (HSM) sentence test in quiet and in noise (65
      dB SPL speech level; 15 dB signal-to-noise ratio, SNR), and a speech tracking
      test with and without lip-reading. RESULTS: An average increase of 20 percentage
      points was scored at discharge compared to the admission tests. Patients of all
      ages and duration of deafness demonstrated the same amount of benefit from the
      rehabilitation treatment. After completion of inpatient rehabilitation treatment,
      patients with short duration of CI experience (below 4 months) achieved test
      scores comparable to experienced long-term users. The demonstrated benefit of the
      treatment was independent of age and duration of deafness or CI experience.
      CONCLUSION: The rehabilitative training program significantly improved hearing
      abilities and speech perception in CI users, thus promoting their professional
      and social inclusion. The present results support the efficacy of inpatient
      rehabilitation for CI recipients. Integration of this or similar therapeutic
      concepts in the German catalog of follow-up treatment measures appears justified.

PMID- 26219525
TI  - [Medical examination: Preparation for ENT specialisation: Part 20].

PMID- 26219523
TI  - [Malignant head and neck melanoma: Part 2: Therapy].
AB  - Resection margins of melanomas in the head and neck region often have to be
      adapted according anatomical circumstances. In the case of thicker primary tumors
      or after complete resection of locoregional lymph node metastases, adjuvant
      therapy with interferon-alpha can be performed; in some cases, adjuvant
      radiotherapy may also be indicated. In the case of inoperable lymph node or
      distant metastases, systemic treatment is required. Beside well-established mono-
      or polychemotherapy regimens, newer targeted therapies with BRAF inhibitors
      (vemurafenib, dabrafenib), mitogenic-activated protein kinase (MEK) inhibitors
      (trametinib, binimetinib, and cobimetinib), and kinase inhibitors (imatinib,
      sunitinib, nilotinib, dasatinib) are also available. 

PMID- 26219526
TI  - [Pre- and posttreatment results of an inpatient neurotologic and psychosomatic
      tinnitus therapy].
AB  - BACKGROUND: Inpatient treatment of chronic complex tinnitus can be necessary for
      patients with a high symptomatic strain, mostly accompanied by a corresponding
      mental comorbidity, and/or for patients that can only perceive their psychogenic
      suffering through somatization into tinnitus. METHODS: We report the results of
      368 consecutively treated inpatients with chronic complex tinnitus. Patients'
      audiometric data were collected, and at the beginning and end of treatment, the
      Mini-Tinnitus Questionnaire (Mini-TQ12; Hiller und Goebel) was completed, as was
      the German version of the Hospitality Anxiety and Depression Score (HADS). Effect
      sizes were calculated for both questionnaires. Mean treatment duration was 38.8
      days (standard deviation, SD: 13.6 days). The main therapeutic elements were
      intensive disorder-specific neurotologic counselling and psychoeducation;
      improvement of hearing by fitting of hearing aids, complemented by an
      individualized hearing therapy; and intensive individual and group-based
      psychotherapy. RESULTS: In addition to tinnitus, 82.1% of the patients had
      reduced hearing requiring rehabilitation with hearing aids. After
      hospitalization, a highly significant improvement in tinnitus strain could be
      demonstrated by the Mini-TQ12. Furthermore, a significant reduction in the
      depression and anxiety components of HADS was also achieved, with high effect
      sizes of 1.6 to 2.2. No reduction of tinnitus symptoms to a medium- or low-range
      level was experienced by 8.9% of patients. CONCLUSION: With corresponding
      symptomatic suffering, disorder-specific inpatient tinnitus treatment comprising
      neurotologic and psychosomatic alignment can achieve medium- to high-range
      therapeutic effects.

PMID- 26219527
TI  - Editorial: Time as presence and opportunity: the key to spiritual care in
      contemporary nursing practice.

PMID- 26219528
TI  - Long-evolution ascites in a patient with constrictive pericarditis.
AB  - Constrictive pericarditis (CP) is an uncommon disease resulting from chronic
      pericardial inflammation, fibrosis and calcification. Once there are atypical
      forms of presentation, with subtle or nonexistent cardiorespiratory symptoms,
      diagnosis may be challenging and difficult. Recurrent ascites in patients with
      congestive hepatopathy due to constrictive pericarditis is common and, in most
      cases, reversible after pericardiectomy. Nevertheless, development of persistent
      liver dysfunction may be a long-term complication. The present work describes a
      23 years old man with growth delay, dyspnoea and long evolution ascites, whose
      exhaustive etiological investigation led to diagnosis. Afterwards the patient
      underwent elective surgery with symptom and general condition improvement.
      Ascites differential diagnosis and its association with constrictive pericarditis
      are briefly reviewed in this article. 

PMID- 26219529
TI  - A meta-analysis of literacy and language in children with rolandic epilepsy.
AB  - AIM: Rolandic epilepsy is the most common childhood epilepsy, often presenting
      with neuropsychological impairments. The aim of the study was to formally
      assimilate the findings of existing studies varying widely in methodology,
      thereby confirming the nature and prevalence of impairments in literacy and
      language. METHODS: Using meta-analytical techniques, we evaluated 22 studies of
      literacy and/or language skills in children with rolandic epilepsy, published
      after 2000, among participants with IQs>70 and in which effect sizes could be
      acquired. Diagnosis required the presence of classical centrotemporal spikes
      arising from a normal background on electroencephalograms; a clinical history
      including at least one seizure; and no additional neurological condition. Overall
      effect size and heterogeneity were measured for single-word reading, phonological
      processing, and expressive and receptive language. RESULTS: Mean effect sizes
      (Cohen's d) ranged from 0.50 (95% confidence interval [CI] 0.23-0.78) for
      phonological processing, through 0.71 (95% CI 0.52-0.90) for word reading and
      0.72 (95% CI 0.34-1.1) for receptive language, to 0.75 (95% CI 0.45-1.05) for
      expressive language. While group differences for reading measures were
      consistent, those for language were heterogeneous and varied across studies
      explained by age and IQ of samples. INTERPRETATION: The presence of reading and
      phonological processing deficits in children with rolandic epilepsy highlights
      the importance of early literacy and language assessment in this population.

PMID- 26219531
TI  - A lactate-derived chiral aldehyde for determining the enantiopurity of
      enantioenriched primary amines.
AB  - In this paper we describe the use of a chiral aldehyde derived from lactate
      esters for determining the enantiopurity of primary amines, via the formation of
      diastereomeric imines. The method was shown to be suitable for reproducibly
      determining the enantiopurity of a diverse set of chiral amines. Both enantiomers
      of the aldehyde can be prepared in two steps from commercially available
      materials. 

PMID- 26219530
TI  - Suppression of IGF-I signals in neural stem cells enhances neurogenesis and
      olfactory function during aging.
AB  - Downregulation of insulin-like growth factor (IGF) pathways prolongs lifespan in
      various species, including mammals. Still, the cellular mechanisms by which IGF
      signaling controls the aging trajectory of individual organs are largely unknown.
      Here, we asked whether suppression of IGF-I receptor (IGF-1R) in adult stem cells
      preserves long-term cell replacement, and whether this may prevent age-related
      functional decline in a regenerating tissue. Using neurogenesis as a paradigm, we
      showed that conditional knockout of IGF-1R specifically in adult neural stem
      cells (NSC) maintained youthful characteristics of olfactory bulb neurogenesis
      within an aging brain. We found that blocking IGF-I signaling in neural
      precursors increased cumulative neuroblast production and enhanced neuronal
      integration into the olfactory bulb. This in turn resulted in neuro-anatomical
      changes that improved olfactory function. Interestingly, mutants also displayed
      long-term alterations in energy metabolism, possibly related to IGF-1R deletion
      in NSCs throughout lifespan. We explored Akt and ERK signaling cascades and
      revealed differential regulation downstream of IGF-1R, with Akt phosphorylation
      preferentially decreased in IGF-1R(-/-) NSCs within the niche, and ERK pathway
      downregulated in differentiated neurons of the OB. These challenging experimental
      results were sustained by data from mathematical modeling, predicting that
      diminished stimulation of growth is indeed optimal for tissue aging. Thus,
      inhibiting growth and longevity gene IGF-1R in adult NSCs induced a gain-of
      function phenotype during aging, marked by optimized management of cell renewal,
      and enhanced olfactory sensory function. 

PMID- 26219532
TI  - A new TLC bioautographic assay for qualitative and quantitative estimation of
      lipase inhibitors.
AB  - INTRODUCTION: Lipase inhibitory assays based on TLC bioautography have made
      recent progress; however, an assay with greater substrate specificity and
      quantitative capabilities would advance the efficacy of this particular bioassay.
      OBJECTIVE: To address these limitations, a new TLC bioautographic assay for
      detecting lipase inhibitors was developed and validated in this study. METHODS:
      The new TLC bioautographic assay was based on reaction of lipase with beta
      naphthyl myristate and the subsequent formation of the purple dye between beta
      naphthol and Fast Blue B salt (FBB). The relative lipase inhibitory capacity
      (RLIC) was determined by a TLC densitometry with fluorescence detection,
      expressed as orlistat equivalents in millimoles on a per sample weight basis. Six
      pure compounds and three natural extracts were evaluated for their potential
      lipase inhibitory activities by this TLC bioautographic assay. RESULTS: The beta
      naphthyl myristate as the substrate improved the detection sensitivity and
      specificity significantly. The limit of detection (LOD) of this assay was 0.01 ng
      for orlistat, the current treatment for obesity. This assay has acceptable
      accuracy (92.07-105.39%), intra-day and inter-day precisions [relative standard
      deviation (RSD), 2.64-4.40%], as well as intra-plate and inter-plate precisions
      (RSD, 1.8-4.9%). CONCLUSION: The developed method is rapid, simple, stable, and
      specific for screening and estimation of the potential lipase inhibitors.

PMID- 26219533
TI  - One-step fabrication of multifunctional micromotors.
AB  - Although artificial micromotors have undergone tremendous progress in recent
      years, their fabrication normally requires complex steps or expensive equipment.
      In this paper, we report a facile one-step method based on an emulsion solvent
      evaporation process to fabricate multifunctional micromotors. By simultaneously
      incorporating various components into an oil-in-water droplet, upon
      emulsification and solidification, a sphere-shaped, asymmetric, and
      multifunctional micromotor is formed. Some of the attractive functions of this
      model micromotor include autonomous movement in high ionic strength solution,
      remote control, enzymatic disassembly and sustained release. This one-step,
      versatile fabrication method can be easily scaled up and therefore may have great
      potential in mass production of multifunctional micromotors for a wide range of
      practical applications. 

PMID- 26219534
TI  - BMC Ecology Image Competition 2015: the winning images.
AB  - For the third time, BMC Ecology is delighted to announce the winners of our Image
      Competition. This year featured entries from all over the world and showcased not
      only the creativity and talent of the participants, but also the exquisite beauty
      and diversity of our planet. We are pleased to present the winning selections of
      the editorial board of the journal and guest judge Dr. Ana Luz Porzecanski, as
      well as some highly commended images that are sure to impress. 

PMID- 26219535
TI  - Mosaic paternal genome-wide uniparental isodisomy with down syndrome.
AB  - We report on a 6-month-old girl with two apparent cell lines; one with trisomy
      21, and the other with paternal genome-wide uniparental isodisomy (GWUPiD),
      identified using single nucleotide polymorphism (SNP) based microarray and
      microsatellite analysis of polymorphic loci. The patient has Beckwith-Wiedemann
      syndrome (BWS) due to paternal uniparental disomy (UPD) at chromosome location
      11p15 (UPD 11p15), which was confirmed through methylation analysis.
      Hyperinsulinemic hypoglycemia is present, which is associated with paternal UPD
      11p15.5; and she likely has medullary nephrocalcinosis, which is associated with
      paternal UPD 20, although this was not biochemically confirmed. Angelman syndrome
      (AS) analysis was negative but this testing is not completely informative; she
      has no specific features of AS. Clinical features of this patient include:
      dysmorphic features consistent with trisomy 21, tetralogy of Fallot,
      hemihypertrophy, swirled skin hyperpigmentation, hepatoblastoma, and Wilms tumor.
      Her karyotype is 47,XX,+21[19]/46,XX[4], and microarray results suggest that the
      cell line with trisomy 21 is biparentally inherited and represents 40-50% of the
      genomic material in the tested specimen. The difference in the level of
      cytogenetically detected mosaicism versus the level of mosaicism observed via
      microarray analysis is likely caused by differences in the test methodologies.
      While a handful of cases of mosaic paternal GWUPiD have been reported, this
      patient is the only reported case that also involves trisomy 21. Other GWUPiD
      patients have presented with features associated with multiple imprinted regions,
      as does our patient.

PMID- 26219536
TI  - Neural activity patterns evoked by a spouse's incongruent emotional reactions
      when recalling marriage-relevant experiences.
AB  - Resonance with the inner states of another social actor is regarded as a hallmark
      of emotional closeness. Nevertheless, sensitivity to potential incongruities
      between one's own and an intimate partner's subjective experience is reportedly
      also important for close relationship quality. Here, we tested whether perceivers
      show greater neurobehavioral responsiveness to a spouse's positive (rather than
      negative) context-incongruent emotions, and whether this effect is influenced by
      the perceiver's satisfaction with the relationship. Thus, we used fMRI to scan
      older long-term married female perceivers while they judged either their spouse's
      or a stranger's affect, based on incongruent nonverbal and verbal cues. The
      verbal cues were selected to evoke strongly polarized affective responses. Higher
      perceiver marital satisfaction predicted greater neural processing of the
      spouse's (rather than the strangers) nonverbal cues. Nevertheless, across all
      perceivers, greater neural processing of a spouse's (rather than a stranger's)
      nonverbal behavior was reliably observed only when the behavior was positive and
      the context was negative. The spouse's positive (rather than negative) nonverbal
      behavior evoked greater activity in putative mirror neuron areas, such as the
      bilateral inferior parietal lobule (IPL). This effect was related to a stronger
      inhibitory influence of cognitive control areas on mirror system activity in
      response to a spouse's negative nonverbal cues, an effect that strengthened with
      increasing perceiver marital satisfaction. Our valence-asymmetric findings imply
      that neurobehavioral responsiveness to a close other's emotions may depend, at
      least partly, on cognitive control resources, which are used to support the
      perceiver's interpersonal goals (here, goals that are relevant to relationship
      stability).

PMID- 26219537
TI  - Dialkyl Ether Formation by Nickel-Catalyzed Cross-Coupling of Acetals and Aryl
      Iodides.
AB  - A new substrate class for nickel-catalyzed C(sp(3)) cross-coupling reactions is
      reported. alpha-Oxy radicals generated from benzylic acetals, TMSCl, and a mild
      reductant can participate in chemoselective cross-coupling with aryl iodides
      using a 2,6-bis(N-pyrazolyl)pyridine (bpp)/Ni catalyst. The mild, base-free
      conditions are tolerant of a variety of functional groups on both partners, thus
      representing an attractive C-C bond-forming approach to dialkyl ether synthesis.
      Characterization of a [(bpp)NiCl] complex relevant to the proposed catalytic
      cycle is also described.

PMID- 26219538
TI  - Randomized equivalence trial: A novel multidose dry powder inhaler and originator
      device in adult and adolescent asthma.
AB  - BACKGROUND: Guideline-defined asthma control can be achieved and maintained in
      patients by treatment with fluticasone propionate-salmeterol (FP-Sal). OBJECTIVE:
      To compare the efficacy and safety of FP-Sal delivered via a novel multidose dry
      powder inhaler (mDPI) versus an originator device in adolescent and adult
      patients with moderate-to-severe persistent asthma. METHODS: Patients ages 12-65
      years (N = 555) were randomized to treatment with FP-Sal novel mDPI 100 MUg-50
      MUg or 500 MUg-50 MUg, or originator device 100 MUg-50 MUg or 500 MUg-50 MUg in a
      double-blind, double-dummy, parallel-group, multicenter study. Primary efficacy
      measures were absolute change in forced expiratory volume in 1 second (FEV1) from
      baseline and the area under the 12-hour serial FEV1 curve at the end of 12 weeks
      of treatment. Secondary end points included mean changes in FEV1; FEV1 %
      predicted; morning predose peak expiratory flow; daytime, nighttime, total asthma
      symptom scores; rescue medication use; percentage of patients with guideline
      defined controlled asthma; global efficacy evaluation; patients' device
      preference; and safety. RESULTS: FP-Sal mDPI and originator device-mediated
      increases in FEV1 from baseline to the end of treatment were not significantly
      different, difference in least squares mean, -0.065 L (95% confidence interval, 
      0.154 to 0.024 L) at 100 MUg-50 MUg, and -0.032 L (95% confidence interval, 
      0.121 to 0.057 L) at 500 MUg-50 MUg). Both doses of FP-Sal mDPI improved FEV1
      area under the 12-hour serial FEV1 curve from baseline and all secondary efficacy
      measures with no significant differences from the originator device at equivalent
      doses, with similar safety profiles. CONCLUSIONS: FP-Sal mDPI demonstrated
      equivalent efficacy and safety profile to the originator device and is an
      alternative in this patient group.

PMID- 26219539
TI  - Betel quid oral lichenoid lesions: a hospital based cross-sectional study.
AB  - OBJECTIVE: The aim of this study was to assess the prevalence and risk indicators
      of betel quid oral lichenoid lesions in chewers. METHODS: A total of 1209 chewers
      were identified and categorized into three main groups based on the type of
      lesion: betel quid oral lichenoid lesions only, betel quid oral lichenoid lesions
      in association with quid-induced other oral mucosal lesions, and no lesions.
      Multinomial regression analyses were used to determine associations between
      dependent and independent variables. RESULTS: Betel quid oral lichenoid lesions
      were more common in individuals who chewed quid comprising both tobacco and areca
      nut, and in those who chewed it two to three, or greater than three, times a day.
      Betel quid oral lichenoid lesions + quid-induced other oral mucosal lesions were
      more likely to occur in females, and in individuals who chewed quid containing
      both tobacco and areca nut, in their processed and unprocessed forms, and greater
      than three times a day. CONCLUSION: The prevalence of betel quid oral lichenoid
      lesions was higher than that reported in previous studies conducted in India.
      Increase in the frequency and duration of quid chewing was associated with
      increased likelihood of developing these oral lichenoid lesions.

PMID- 26219540
TI  - Nanocrystal-constructed mesoporous CoFe2O4 nanowire arrays aligned on flexible
      carbon fabric as integrated anodes with enhanced lithium storage properties.
AB  - A novel and facile two-step strategy is successfully developed for the large
      scale fabrication of hierarchical mesoporous CoFe2O4 nanowire arrays (NWAs) on
      flexible carbon fabric as integrated anodes for highly efficient and reversible
      lithium storage. The synthesis involves the co-deposition of uniform bimetallic
      (Co, Fe) carbonate hydroxide hydrate precursor NWAs on carbon fabric and
      subsequent thermal transformation to spinel CoFe2O4 without damaging the
      morphology. The as-prepared CoFe2O4 nanowires have unique mesoporous structures,
      which are constructed by many interconnected nanocrystals with sizes of about 15
      20 nm. The typical size of the nanowires is in the range of 70-100 nm in width
      and up to several micrometers in length. Such a hybrid nanostructure electrode
      presented here not only simplifies electrode processing, but also promises fast
      electron transport/collection and ion diffusion, and withstands volume variation
      upon prolonged charge/discharge cycling. As a result, the binder-free
      CoFe2O4/carbon fabric composite exhibits a high reversible capacity of 1185.75 mA
      h g(-1) at a current density of 200 mA g(-1), and a superior rate capability.
      More importantly, a reversible capacity as high as ~950 mA h g(-1) can be
      retained and there is no obvious decay after 150 cycles. 

PMID- 26219541
TI  - CADM1 and MAL methylation status in cervical scrapes is representative of the
      most severe underlying lesion in women with multiple cervical biopsies.
AB  - Recent studies have shown that CADM1/MAL methylation levels in cervical scrapes
      increase with severity and duration of the underlying cervical intraepithelial
      neoplasia (CIN) lesion. Multiple lesions of different histological grades and
      duration are frequently present on the cervix. To gain more insight into the
      possible epigenetic heterogeneity and its consequences for the methylation status
      in cervical scrapes, we performed an exploratory study of CADM1/MAL methylation
      in different grades of CIN lesions present in women with multiple cervical
      biopsies. CADM1-M18 and MAL-M1 methylation was assessed using a standardised,
      multiplex, quantitative methylation specific PCR on 178 biopsies with various
      grades of CIN in 65 women, and in their corresponding cervical scrapes. CADM1/MAL
      methylation positivity increased with disease severity, from 5.5% in normal
      biopsies to 63.3% and 100% in biopsies with CIN3 and cervical cancer,
      respectively. In the majority (8/9) of women where besides a CIN2/3 lesion a
      biopsy from normal cervical tissue was present, the CIN2/3 biopsy was CADM1/MAL
      methylation positive and the normal biopsy was CADM1/MAL methylation negative. A
      good concordance (78%) was found between CADM1/MAL methylation results on the
      scrapes and the biopsy with the worst diagnosis, particularly between samples of
      women with CIN3 and cervical cancer (92% and 100% concordance, respectively).
      Thus, in women with multiple cervical biopsies, CADM1/MAL methylation increases
      with severity of the lesion and is lesion-specific. CADM1/MAL methylation status
      in cervical scrapes appears to be representative of the worst underlying lesion,
      particularly for CIN3 and cervical cancer. 

PMID- 26219542
TI  - Mitochondria-acting hexokinase II peptides carried by short-length carbon
      nanotubes with increased cellular uptake, endosomal evasion, and enhanced
      bioactivity against cancer cells.
AB  - Type II hexokinase (HKII) has emerged as a viable therapeutic target due to its
      involvement in metabolic reprogramming and also apoptosis prevention. The peptide
      derived from the fifteen amino acid sequence in the HKII N-terminal region
      [HKII(pep)] can compete with endogenous proteins for binding on mitochondria and
      trigger apoptosis. However, this peptide is not cell-permeable. In this study,
      multi-walled carbon nanotubes (MWCNTs) were used to effectively deliver HKII(pep)
      across cellular barriers without compromising their bioactivity. The peptide was
      conjugated on either oxidized MWCNTs or 2,2'-(ethylenedioxy)bis(ethylamine)
      functionalized MWCNTs, yielding MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep),
      respectively. Both conjugates were shown to be internalized by breast cancer MCF
      7 cells using confocal microscopy. Moreover, these nanoconjugates seemed to have
      escaped from endosomes and be in the vicinity of mitochondria. The WST-1
      cytotoxicity assay conducted on MCF-7 and colon carcinoma HCT116 cells revealed
      that MWCNT-peptide conjugates were significantly more effective in curbing cancer
      cell growth compared to a commercially available cell permeable HKII fusion
      peptide. In addition, both nanoconjugates displayed an enhanced ability in
      eliciting apoptosis and depleting the ATP level in HCT116 cells compared to the
      mere HKII peptide. Importantly, hexokinase II release from mitochondria was
      demonstrated in MWCNT-HKII(pep) and MWCNT-TEG-HKII(pep) treated cells,
      highlighting that the structure and bioactivity of HKII(pep) were not compromised
      after covalent conjugation to MWCNTs. 

PMID- 26219543
TI  - Aggregation induced phosphorescent N-oxyde-2,2'-bipyridine bismuth complexes and
      polymorphism-dependent emission.
AB  - Unprecedented bismuth complexes, based on the rarely used ditopic ligand N-oxide
      2,2'-bipyridine (bp2mo), crystallizing as three polymorphs, alpha- (), beta- ()
      and gamma-[BiBr3(bp2mo)2] (), exhibit phosphorescence with a quantum yield up to
      17% for the crystal phase (), while the complex displays a weak fluorescence in
      solution. A study of the luminescence properties combined with DFT/TDDFT
      calculations reveals that the lighting phenomenon originated by aggregation
      induced phosphorescence correlated with the weak intermolecular interactions
      present in the different crystal phases. 

PMID- 26219544
TI  - Complications and outcome of a new modified Maquet technique for treatment of
      cranial cruciate ligament rupture in 82 dogs.
AB  - OBJECTIVES: To describe the complications, short and long-term outcome and owner
      satisfaction of dogs with cranial cruciate ligament rupture treated with a
      recently described new osteotomy for the modified Maquet technique (N-MMT).
      MATERIALS AND METHODS: Medical records and radiographs of 82 dogs (84 stifles)
      were reviewed. Details regarding short-term outcome and complications were
      recorded from the medical records. Long-term follow-up information was obtained
      by telephone interview. Historical data and complications were statistically
      analysed. RESULTS: Major complications occurred in 34/84 stifles. Intra-operative
      complications occurred in 26/84 stifles, all of which were fissures or fractures
      of the cortical hinge. Twenty-one of these fractures or fissures were repaired
      with a figure-of-eight wire. The second most common major complication was late
      meniscal tears in 3/84 stifles. One dog sustained a complete tibial fracture. Non
      displaced fracture of the cortical hinge was the most common postoperative minor
      complication, which occurred in 5/84 stifles. The median preoperative lameness
      score was 3 out of 6. Final in-hospital re-evaluation of limb function was
      available in 58 dogs. The median lameness score at that time was 0 out of 6.
      Development of osteotomy related complications was not associated with a
      significant change in the postoperative lameness score. CLINICAL SIGNIFICANCE:
      Subjectively assessed clinical outcome with the N-MMT was good to excellent in
      this cohort of dogs. However, a high rate of intra- and postoperative
      complications of the N-MMT procedure was also present in these dogs.

PMID- 26219545
TI  - Salininema proteolyticum gen. nov., sp. nov., a halophilic rare actinomycete
      isolated from wetland soil, and emended description of the family
      Glycomycetaceae.
AB  - A Gram-stain-positive actinobacterial strain, Miq-4T, was isolated from soil
      around Meighan wetland in the centre of Iran. Strain Miq-4T was strictly aerobic,
      catalase- and oxidase-positive. The isolate grew in the presence of 3-15 % (w/v)
      NaCl, at 20-40  degrees C and pH 6.0-11.0. The optimum NaCl, temperature and pH
      for growth were 7.0 %, 30  degrees C and 7.0-8.5, respectively. The cell wall of
      strain Miq-4T contained meso-diaminopimelic acid as the diamino acid and glucose
      and ribose as the whole-cell sugars. The polar lipid pattern consisted of
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylinositol and phosphatidylinositol mannoside. Strain Miq-4T
      synthesized cellular fatty acids of anteiso- and iso-branched types, including
      anteiso-C17 : 0, anteiso- C15 : 0 and iso-C16 : 0, and the major respiratory
      quinone was MK-9(H4). The G+C content of the genomic DNA was 68.2 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences and characteristic
      patterns of 16S rRNA gene signature nucleotides revealed that strain Miq-4T
      belongs to the family Glycomycetaceae and showed the closest phylogenetic
      similarity with Haloglycomyces albus YIM 92370T (94.1 % 16S rRNA gene sequence
      similarity). On the basis of phylogenetic analysis and phenotypic and
      chemotaxonomic characteristics, strain Miq-4T represents a novel species of a new
      genus in the family Glycomycetaceae, for which the name Salininema proteoliyticum
      gen. nov., sp. nov. is proposed. The type strain of the type species is Miq-4T (
      = IBRC-M 10908T = LMG 28391T). An emended description of the family
      Glycomycetaceae is also proposed in order to include features of the new genus.

PMID- 26219546
TI  - The molecular and electronic structures of a thioaroyl cation formed by borinium
      ion-mediated C=S double bond cleavage of CS2.
AB  - The first crystallographic and electron density distribution analyses of a
      thioaroyl cation unveil its true structural perspective; this chemical species
      can be mainly expressed as the combination of the thioketene form (II) and
      sulfonium form (III) with a C=S(+) triple bond character.

PMID- 26219547
TI  - Nasal balloon shows promise for otitis media with effusion.

PMID- 26219548
TI  - Physician involvement in life transition planning: a survey of community-dwelling
      older adults.
AB  - BACKGROUND: With many information sources for healthy aging and life transitions,
      it is unknown whether community-dwelling older adults desire physician
      involvement in future planning decisions. The study aimed to examine older
      adults' experiences and opinions concerning four future planning domains: advance
      care planning, driving, finances, and housing. METHODS: Adults aged >=55 years
      living at a large urban, independent living facility were surveyed with an
      anonymous, voluntary, paper-based, mailed questionnaire. Survey domains were
      advance care planning, driving, finances, and housing. For each domain, questions
      assessed confidence, openness to discussions, information sources, and prior and
      desired future role of the physician in decision-making by domain. Comparisons
      across and within domains were determined using Chi-square tests. RESULTS: The
      response rate was 56 % (N = 457; median age: 75 years; 74 % female). Among
      advance care planning, driving, and finances, respondents were more confident
      about what it means to have an advance directive (87 %, 95 % CI 84 - 90 %) than
      alternative transportation options (46 %, 95 % CI 42 - 51 %). Nearly two-thirds
      of respondents (64 %, 95 % CI 59 - 68 %) were open to discussing driving
      cessation, though only one-third (32 %, 95 % CI 28 - 37 %) were open to having a
      family member determine timing of driving cessation. More individuals (44 %, 95 %
      CI 39 - 49 %) were open to a physician deciding about when to stop driving. Past
      discussions with family or friends about advance care planning or finances were
      common, although past discussions about driving were less common. Respondents
      reported personal experience and family as key information sources, which were
      significantly more common than healthcare providers. While prior involvement by
      physicians in decision-making was rare across all domains, some respondents
      expressed desire for future physician involvement in all domains, with advance
      care planning (29 %, 95 % CI 25 - 33 %) and driving safety (24 %, 95 % CI 20 - 28
      %) having highest levels of support for future physician involvement.
      CONCLUSIONS: Some older adults desired more physician involvement in future
      planning for life transitions, especially related to advance care planning and
      driving compared to finances and housing. Clinical implications include increased
      patient-centered care and anticipatory guidance by physicians for aging-related
      life transitions.

PMID- 26219550
TI  - Maternal and fetal arterial blood gas data during general anaesthesia for
      caesarean delivery of preterm twin lambs.
AB  - Much remains to be understood with regards the effects of prolonged anaesthesia
      on maternal and fetal haemodynamics and oxygenation. With the aim of improving
      anaesthetic management of pregnant sheep undergoing recovery surgery under
      anaesthesia, paired maternal and fetal arterial blood samples were collected
      during caesarean delivery of twin preterm lambs to document the blood gas status
      of the ewe and fetus. Twenty-one Merino twin pregnant ewes at 126 (+/-1) days of
      gestation were anaesthetized for caesarean delivery of their fetuses. Arterial
      blood samples were collected from the radial artery of the ewe and umbilical
      artery of the fetus at the point of delivery. There was a significant difference
      between maternal PaCO2 and end-tidal CO2 and alveolar and arterial PaO2,
      indicating ventilation perfusion mismatch. Interestingly, the ewes were anaemic
      but the fetuses were not. These data underscore the need to undertake further
      work to determine the optimal anaesthetic regimen for twin pregnant ewes at
      different gestational ages in a biomedical research setting. 

PMID- 26219549
TI  - Comparison of short-term effects between face mask and skeletal anchorage therapy
      with intermaxillary elastics in patients with maxillary retrognathia.
AB  - INTRODUCTION: The aim of this study was to compare the short-term dental and
      skeletal effects of a face mask (FM) with those of skeletal anchorage (SA)
      therapy with intermaxillary elastics in prepubertal patients with skeletal Class
      III malocclusion. METHODS: Fifty patients with skeletal Class III malocclusion
      and maxillary deficiency were divided into two groups. In the FM group, an FM was
      applied by a bite plate with a force of 400g for each side. In the SA group, mini
      plates were placed between mandibular lateral incisors and canines, and mini
      implants were inserted between maxillary second premolars and first molars. A
      bite plate was inserted into the upper arch, and Class III elastics were applied
      with a force of 200g between each mini-plate and mini-implant. RESULTS: Mean
      treatment durations were 0.52+/-0.09 years for FM and 0.76+/-0.09 years for SA.
      After the treatment, statistically significant increases in SNA degrees , ANB
      degrees , A-y, 1-NA, SnGoGn degrees , Co-A, Co-Gn, and A-Nperp, and reductions in
      SNB degrees  and FH?N-Pg were observed in both groups, and these changes were
      similar in both groups. In the FM group, 1-NB decreased significantly, and in the
      SA group, it increased significantly (P < 0.05). CONCLUSIONS: The undesired
      dentoalveolar effects of the FM treatment were eliminated with SA treatment,
      except with regard to lower incisor inclination. Favourable skeletal outcomes can
      be achieved by SA therapies, which could be an alternative to the extraoral
      appliances frequently applied to treat skeletal Class III patients with maxillary
      deficiency.

PMID- 26219552
TI  - Pain medication use after spine surgery: is it assessed in the literature? A
      systematic review, January 2000-December 2009.
AB  - BACKGROUND: Spine surgery is one of the most difficult areas in which to achieve
      a good clinical outcome and pain medication is often used for a long period of
      time after surgery. The purpose of this study was to investigate whether pain
      medication use after spine surgery has been assessed previously with respect to
      clinical outcome. METHODS: A systematic review of PubMed/MEDLINE databases was
      conducted from Jan 1st 2000 to Dec 31st 2009 using the search key words, "spine
      surgery" and "clinical outcome." All publications reporting clinical outcomes
      were examined and analyzed for outcome measures and data with respect to pain
      medication use after spine surgery. RESULTS: In total 990 articles met the
      inclusion criteria. Among them, 56 articles (5.7%) described definitive pain
      medication use after spine surgery; 98 articles (9.9%) used clinical outcome
      measures that incorporate pain medication assessment, although only one such
      study included a definitive description of pain medication use. CONCLUSIONS: Pain
      medication use after spine surgery was assessed in 15.5% of articles published
      during the last decade. The use of pain medication following spine surgery can
      affect clinical outcome and, therefore, needs to be taken into consideration for
      clinical assessment. In future studies, a detailed description of pain medication
      use and/or clinical outcome measures that incorporate pain medication assessment
      are advocated when reporting clinical outcomes after spine surgery so that it can
      be better assessed.

PMID- 26219551
TI  - Combined Trabectedin and anti-PD1 antibody produces a synergistic antitumor
      effect in a murine model of ovarian cancer.
AB  - BACKGROUND: Monoclonal antibodies (mAb) that block programmed death (PD)-1
      signaling pathway hold great potential as a novel cancer immunotherapy. Recent
      evidence suggests that combining with conventional, targeted or other
      immunotherapies, these mAb can induce synergistic antitumor responses. In this
      study, we investigated whether Trabectedin (ET-743), a novel anticancer agent
      currently used for treating relapsed ovarian cancer, can synergize with anti
      (alpha)-PD-1 mAb to increase antitumor activity in the murine ID8 ovarian cancer
      model. METHODS: Mice with established peritoneal ID8 tumor were treated with
      either single or combined Trabectedin and alpha-PD-1 mAb, their overall survival
      was recorded; tumor-associated immune cells and immune gene expression in tumors
      from treated mice were analyzed by flow cytometry and quantitative RT-PCR,
      respectively, and antigen-specific immunity of effector CD8(+) T cells was
      evaluated by ELISA and cytotoxicity assay. In addition, the effect of Trabectedin
      on tumoral PD-L1 expression was analyzed by both flow cytometry and
      immunofluorescence staining. RESULTS: Though single treatment showed a modest
      antitumor effect in mice bearing 10-day-established ID8 tumor, combined
      Trabectedin and alpha-PD-1 mAb treatment induced a strong antitumor immune
      response, leading to a significant tumor regression with half of mice tumor-free
      90 days after tumor inoculation. Mechanistic investigation revealed that
      combination treatment induces a systemic tumor-specific immunity with an
      indispensable role of both CD4(+) and CD8(+) T cells, and effector CD8(+) T cells
      exhibited the antigen-specific cytokine secretion and cytotoxicity upon tumor
      antigen stimulation; additionally, combination treatment increased the IFN-gamma
      producing effector T cells and decreased the immunosuppressive cells in
      peritoneal cavity; accordingly, it enhanced the expression of Th1-associated
      immune-stimulating genes while reducing the transcription of
      regulatory/suppressive immune genes, reshaping tumor microenvironment from a
      immunosuppressive to a stimulatory state. Finally, in vivo Trabectedin treatment
      has been shown to induce IFN-gamma-dependent PD-L1 expression within tumor,
      possibly constituting a mechanistic basis for its synergistic antitumor effect
      with alpha-PD-1 mAb therapy. CONCLUSION: This study provides the evidence that
      alpha-PD-1 mAb can produce a synergistic antitumor efficacy when combined with
      Trabectedin, a clinically available anticancer agent, supporting a direct
      translation of this combination strategy in clinic for the treatment of ovarian
      cancer.

PMID- 26219553
TI  - Genetically-encoded sensors of protein hydrodynamics.

PMID- 26219554
TI  - mTORtuous effect on the elastic heart.

PMID- 26219555
TI  - Antimicrobial peptides target ribosomes.

PMID- 26219556
TI  - DNA repair: location, location, location.

PMID- 26219557
TI  - ETV6 mutations define a new cancer predisposition syndrome.

PMID- 26219558
TI  - Haploinsufficiency of Bcl11b suppresses the progression of ATM-deficient T cell
      lymphomas.
AB  - Bcl11b is a transcription factor important for T cell development and also a
      tumor-suppressor gene that is hemizygously inactivated in ~10% human T cell acute
      lymphoblastic leukemia (T-ALL) and several murine T-ALL models, including ATM(-/
      ) thymic lymphomas. Here we report that heterozygous loss of Bcl11b (Bcl11b(+/-))
      unexpectedly reduced lethal thymic lymphoma in ATM(-/-) mice by suppressing
      lymphoma progression, but not initiation. The suppression was associated with a T
      cell-mediated immune response in ATM(-/-)Bcl11b(+/-) mice, revealing a haploid
      insufficient function of Bcl11b in immune modulation against lymphoma and
      offering an explanation for the complex relationship between Bcl11b status with T
      ALL prognosis.

PMID- 26219559
TI  - Urbanization, Extreme Events, and Health: The Case for Systems Approaches in
      Mitigation, Management, and Response.
AB  - Extreme events, both natural and anthropogenic, increasingly affect cities in
      terms of economic losses and impacts on health and well-being. Most people now
      live in cities, and Asian cities, in particular, are experiencing growth on
      unprecedented scales. Meanwhile, the economic and health consequences of climate
      related events are worsening, a trend projected to continue. Urbanization,
      climate change and other geophysical and social forces interact with urban
      systems in ways that give rise to complex and in many cases synergistic
      relationships. Such effects may be mediated by location, scale, density, or
      connectivity, and also involve feedbacks and cascading outcomes. In this context,
      traditional, siloed, reductionist approaches to understanding and dealing with
      extreme events are unlikely to be adequate. Systems approaches to mitigation,
      management and response for extreme events offer a more effective way forward.
      Well-managed urban systems can decrease risk and increase resilience in the face
      of such events. 

PMID- 26219560
TI  - Social Influences of Help-Seeking Behaviour Among Patients With Type 2 Diabetes
      Mellitus in Malaysia.
AB  - This qualitative study aimed to explore the influence of social networks such as
      family members, friends, peers, and health care providers toward the help-seeking
      behaviour (HSB) of patients with type 2 diabetes mellitus in the public and
      private primary care settings. In-depth interviews of 12 patients, 9 family
      members, and 5 health care providers, as well as 3 focus groups among 13 health
      care providers were conducted. All interviews were audio-taped and transcribed
      verbatim for qualitative analysis. Social influences play a significant role in
      the help-seeking process; once diagnosed, patients source information from people
      around them to make decisions. This significant influence depends on the
      relationship between patients and social networks or the level of trust, support,
      and comforting feeling. Thus, the impacts on patients' help-seeking behavior are
      varied. However, the help-seeking process is not solely an individual's concern
      but a dynamic process interacting with the social networks within the health care
      system. 

PMID- 26219561
TI  - Weak Interactions and Instability Cascades.
AB  - Food web theory states that a weak interactor which is positioned in the food web
      such that it tends to deflect, or mute, energy away from a potentially
      oscillating consumer-resource interaction often enhances community persistence
      and stability. Here we examine how adding other weak interactions
      (predation/harvesting) on the stabilizing weak interactor alters the stability of
      food web using a set of well-established food web models/modules. We show that
      such "weak on weak" interaction chains drive an indirect dynamic cascade that can
      rapidly ignite a distant consumer-resource oscillator. Nonetheless, we also show
      that the "weak on weak" interactions are still more stable than the food web
      without them, and so weak interactions still generally act to stabilize food
      webs. Rather, these results are best interpreted to say that the degree of the
      stabilizing effect of a given important weak interaction can be severely
      compromised by other weak interactions (including weak harvesting). 

PMID- 26219562
TI  - Disparity in Mortality From Rheumatic Heart Disease in Indigenous Australians.
AB  - BACKGROUND: Recent estimates of the global burden of rheumatic heart disease
      (RHD) have highlighted the paucity of reliable RHD mortality data from
      populations most affected by RHD. METHODS AND RESULTS: We investigated RHD
      mortality rates and trends for Indigenous and non-Indigenous Australians in the
      Northern Territory (NT) for the period 1977-2005 and seminationally (NT plus 4
      other states, covering 89% of Indigenous Australians) from 1997 to 2005 using
      vital statistics data. All analysis was undertaken by Indigenous status, sex, and
      age at death. In the NT, 90% of all deaths from RHD were among Indigenous
      persons; however, the Indigenous population makes up only 30.4% of the NT
      population. The death rate ratio (Indigenous compared with non-Indigenous) was
      54.80 in the NT and 12.74 in the other 4 states (estimated at the median age of
      50 years). Non-Indigenous death rates were low for all age groups except >=65
      years, indicating RHD deaths in the elderly non-Indigenous population. Death
      rates decreased at a more rapid rate for non-Indigenous than Indigenous persons
      in the NT between 1997 and 2005. Indigenous persons in other parts of Australia
      showed lower death rates than their NT counterparts, but the death rates for
      Indigenous persons in all states were still much higher than rates for non
      Indigenous Australians. CONCLUSIONS: Indigenous Australians are much more likely
      to die from RHD than other Australians. Among the Indigenous population, RHD
      mortality is much higher in the NT than elsewhere in Australia, exceeding levels
      reported in many industrialized countries more than a century ago. With the
      paucity of data from high-prevalence areas, these data contribute substantially
      to understanding the global burden of RHD mortality.

PMID- 26219563
TI  - Association of 6-Minute Walk Performance and Physical Activity With Incident
      Ischemic Heart Disease Events and Stroke in Peripheral Artery Disease.
AB  - BACKGROUND: We determined whether poorer 6-minute walk performance and lower
      physical activity levels are associated with higher rates of ischemic heart
      disease (IHD) events in people with lower extremity peripheral artery disease
      (PAD). METHODS AND RESULTS: Five hundred ten PAD participants were identified
      from Chicago-area medical centers and followed prospectively for 19.0+/-9.5
      months. At baseline, participants completed the 6-minute walk and reported number
      of blocks walked during the past week (physical activity). IHD events were
      systematically adjudicated and consisted of new myocardial infarction, unstable
      angina, and cardiac death. For 6-minute walk, IHD event rates were 25/170 (14.7%)
      for the third (poorest) tertile, 10/171 (5.8%%) for the second tertile, and 6/169
      (3.5%) for the first (best) tertile (P=0.003). For physical activity, IHD event
      rates were 21/154 (13.6%) for the third (poorest) tertile, 15/174 (8.6%) for the
      second tertile, and 5/182 (2.7%) for the first (best) tertile (P=0.001).
      Adjusting for age, sex, race, smoking, body mass index, comorbidities, and
      physical activity, participants in the poorest 6-minute walk tertile had a 3.28
      fold (95% CI 1.17 to 9.17, P=0.024) higher hazard for IHD events, compared with
      those in the best tertile. Adjusting for confounders including 6-minute walk,
      participants in the poorest physical activity tertile had a 3.72-fold (95% CI
      1.24 to 11.19, P=0.019) higher hazard for IHD events, compared with the highest
      tertile. CONCLUSIONS: Six-minute walk and physical activity predict IHD event
      rates in PAD. Further study is needed to determine whether interventions that
      improve 6-minute walk, physical activity, or both can reduce IHD events in PAD.

PMID- 26219564
TI  - Equine immunoglobulins and organization of immunoglobulin genes.
AB  - Our understanding of how equine immunoglobulin genes are organized has increased
      significantly in recent years. For equine heavy chains, 52 IGHV, 40 IGHD, 8 IGHJ
      and 11 IGHC are present. Seven of these IGHCs are gamma chain genes. Sequence
      diversity is increasing between fetal, neonatal, foal and adult age. The kappa
      light chain contains 60 IGKV, 5 IGKJ and 1 IGKC, whereas there are 144 IGLV, 7
      IGLJ, and 7 IGLC for the lambda light chain, which is expressed predominantly in
      horses. Significant transcriptional differences for IGLV and IGLC are identified
      in different breeds. Allotypic and allelic variants are observed for IGLC1,
      IGLC5, and IGLC6/7, and two IGLV pseudogenes are also transcribed. During age
      development, a decrease in IGLVs is noted, although nucleotide diversity and
      significant differences in gene usage increased. The following paper suggests a
      standardization of the existing nomenclature of immunoglobulin genes. 

PMID- 26219565
TI  - Meiothermus roseus sp. nov., a thermophilic bacterium isolated from a geothermal
      area.
AB  - Two closely related thermophilic bacterial strains, designated YIM 71031(T) and
      YIM 71039, were isolated from a hot spring in Tengchong county, Yunnan province,
      south-western China. The novel isolates were observed to be Gram-negative,
      aerobic, rod-shaped and yellow-pigmented bacteria. The strains were found to be
      able to grow at 37-65  degrees C, pH 6.0-9.0 and with a NaCl tolerance up to 1.0
      % (w/v). Phylogenetic analysis based on 16S rRNA gene sequences placed these two
      isolates in the genus Meiothermus. They were found to be closely related to
      Meiothermus timidus DSM 17022(T) (98.6 % similarity), and formed a cluster with
      this species. The predominant menaquinone was identified as MK-8 and the major
      fatty acids (>10 %) as anteiso-C15:0, iso-C15:0, anteiso-C17:0, iso-C16:0 and
      C16:0. The genomic DNA G+C contents of strains YIM 71031(T) and YIM 71039 were
      determined to be 64.0 and 65.4 mol%, respectively. DNA-DNA hybridizations showed
      low values between strains YIM 71031(T) and YIM 71039 and their closely related
      neighbour M. timidus DSM 17022(T). Morphological phylogenetic and chemotaxonomic
      results suggest that strains YIM 71031(T) and YIM 71039 are representatives of a
      new species within the genus Meiothermus, for which the name Meiothermus roseus
      sp. nov. is proposed. The type strain is YIM 71031(T) (=KCTC 42495(T) =NBRC
      110900(T)).

PMID- 26219566
TI  - Xylitol production by yeasts isolated from rotting wood in the Galapagos Islands,
      Ecuador, and description of Cyberlindnera galapagoensis f.a., sp. nov.
AB  - This study evaluated D-xylose-assimilating yeasts that are associated with
      rotting wood from the Galapagos Archipelago, Ecuador, for xylitol production from
      hemicellulose hydrolysates. A total of 140 yeast strains were isolated. Yeasts
      related to the clades Yamadazyma, Kazachstania, Kurtzmaniella, Lodderomyces,
      Metschnikowia and Saturnispora were predominant. In culture assays using
      sugarcane bagasse hemicellulose hydrolysate, Candida tropicalis CLQCA-24SC-125
      showed the highest xylitol production, yield and productivity (27.1 g L(-1)
      xylitol, Y p/s (xyl) = 0.67 g g(-1), Qp = 0.38 g L(-1). A new species of
      Cyberlindnera, strain CLQCA-24SC-025, was responsible for the second highest
      xylitol production (24 g L(-1), Y p/s (xyl) = 0.64 g g(-1), Qp = 0.33 g L(-1) h(
      1)) on sugarcane hydrolysate. The new xylitol-producing species Cyberlindnera
      galapagoensis f.a., sp. nov., is proposed to accommodate the strain CLQCA-24SC
      025(T) (=UFMG-CM-Y517(T); CBS 13997(T)). The MycoBank number is MB 812171.

PMID- 26219567
TI  - Genetic evaluation of a selective breeding program for common carp Cyprinus
      carpio conducted from 2004 to 2014.
AB  - BACKGROUND: The study evaluated genetic progress of a breeding program for common
      carp undergoing four generations of selection for increased harvest body weight
      from 2004 to 2014. The pedigree included 17,351 individual fish which were
      offspring of 342 sires and 352 dams. Genetic parameters for body weight at about
      two years of age and survival rate during grow-out period were also estimated
      using the residual maximum likelihood method applied to a two-trait linear mixed
      model. Direct response in body weight and correlated changes in survival were
      measured as the differences in: i) estimated breeding values (EBVs) between the
      two lines; and ii) EBVs of the selection line between successive generations.
      RESULTS: Direct gain in body weight ranged from 0.20 to 0.90 genetic standard
      deviation units and averaged 7 % of the base population per generation (two years
      per generation). Correlated changes in survival were negligible, indicating that
      the selection program for high growth did not have any adverse effect on this
      trait in the present population. The heritability for body weight was moderate
      (0.17, s.e. 0.05), whereas the estimate for survival was low (0.05-0.17) but
      significantly different from zero across linear mixed and threshold generalised
      statistical models. Our results predict that body weight or/and other growth
      related traits will continue to respond to selection and that there is potential
      to improve survival through direct genetic means. Correlated improvement in
      survival to selection for increased body weight was hardly achieved, as the
      genetic correlation between the two traits was not different from zero.
      CONCLUSIONS: It is concluded that selection for increased harvest body weight
      resulted in significant improvement in growth performance of the present
      population of common carp Cyprinus carpio.

PMID- 26219568
TI  - Potential surrogate endpoints for overall survival in locoregionally advanced
      nasopharyngeal carcinoma: an analysis of a phase III randomized trial.
AB  - The gold standard endpoint in trials of locoregionally advanced nasopharyngeal
      carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized
      trial, we evaluated whether progression-free survival (PFS), failure-free
      survival (FFS), distant failure-free survival (D-FFS) or locoregional failure
      free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July
      2002 and September 2005, 316 eligible patients with stage III-IVB NPC were
      randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2-
      and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5
      year OS using Prentice's four criteria. The Spearman's rank correlation
      coefficient was calculated to assess the strength of the associations. After a
      median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not
      significantly different between treatment arms, in rejection of Prentice's second
      criterion. Being consistent with all Prentice's criteria, 2- and 3-year PFS and
      FFS were valid surrogate endpoints for 5-year OS; the rank correlation
      coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion,
      PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5
      years; 3-year PFS may be more appropriate for early assessment of long-term
      survival. 

PMID- 26219570
TI  - Editorial overview: Progress and challenges in modeling human viral diseases in
      vivo.

PMID- 26219569
TI  - P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK
      rearrangement.
AB  - BACKGROUND: Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for
      protein stability, Hsp90 inhibitors are effective in controlling growth of lung
      cancer cells with ALK rearrangement. We investigated the mechanism of acquired
      resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a
      geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung
      cancer cell lines with ALK rearrangement. METHODS: Resistant cell lines (H3122/DR
      1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing
      concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone
      oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG
      resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR,
      western blot analysis, chemical inhibitors, the MTT cell proliferation/survival
      assay, and cellular efflux of rhodamine 123. RESULTS: The resistant cells showed
      no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency
      persists in cells with acquired resistance to 17-DMAG. Although expression of
      NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did
      not affect the response of parental cells (H2228 and H3122) to 17-DMAG.
      Interestingly, all resistant cells showed the induction of P-gp at the protein
      and RNA levels, which was associated with an increased efflux of the P-gp
      substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp
      or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to
      the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also
      observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR
      and H460/PR cells generated to over-express P-gp by long-term exposure to
      paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the
      inhibition of P-gp. CONCLUSION: P-gp over-expression is a possible mechanism of
      acquired resistance to 17-DMAG in cells with ALK rearrangement.

PMID- 26219571
TI  - Differences in sensitivity to the fungal pathogen Batrachochytrium dendrobatidis
      among amphibian populations.
AB  - Contributing to the worldwide biodiversity crisis are emerging infectious
      diseases, which can lead to extirpations and extinctions of hosts. For example,
      the infectious fungal pathogen Batrachochytrium dendrobatidis (Bd) is associated
      with worldwide amphibian population declines and extinctions. Sensitivity to Bd
      varies with species, season, and life stage. However, there is little information
      on whether sensitivity to Bd differs among populations, which is essential for
      understanding Bd-infection dynamics and for formulating conservation strategies.
      We experimentally investigated intraspecific differences in host sensitivity to
      Bd across 10 populations of wood frogs (Lithobates sylvaticus) raised from eggs
      to metamorphosis. We exposed the post-metamorphic wood frogs to Bd and monitored
      survival for 30 days under controlled laboratory conditions. Populations differed
      in overall survival and mortality rate. Infection load also differed among
      populations but was not correlated with population differences in risk of
      mortality. Such population-level variation in sensitivity to Bd may result in
      reservoir populations that may be a source for the transmission of Bd to other
      sensitive populations or species. Alternatively, remnant populations that are
      less sensitive to Bd could serve as sources for recolonization after epidemic
      events. 

PMID- 26219573
TI  - Screening for Lynch syndrome among patients with newly diagnosed endometrial
      cancer: a comprehensive review.
AB  - Lynch syndrome (LS) is an autosomal dominant condition characterized by an
      increased risk of hereditary colorectal, endometrial, ovarian, pancreatic,
      urinary tract, and gastric cancer.It is estimated that around 5% of all
      endometrial cancer (EC) cases are due to an inherited predisposition, of which LS
      might be the most frequent. The lifetime risk of developing EC in women with LS
      ranges between 40% and 71% depending on the type of mutation. In many cases, this
      risk may even exceed their risk of developing colon cancer. Moreover, in 60% of
      these women, EC will be the first primary malignancy diagnosed and the sentinel
      diagnosis of the syndrome. Therefore, it is essential to identify which women
      with EC have LS in order to allow implementation of individualized screening and
      preventive strategies.

PMID- 26219572
TI  - Systemic chemotherapy followed by locoregional definitive intensity-modulated
      radiation therapy yields prolonged survival in nasopharyngeal carcinoma patients
      with distant metastasis at initial diagnosis.
AB  - Chemotherapy is the current mainstay of treatment for patients with newly
      diagnosed metastatic nasopharyngeal carcinoma (NPC), whereas the role of
      locoregional radiotherapy remains to be defined. In this study, we
      retrospectively evaluated the outcome of systemic chemotherapy followed by
      locoregional definitive intensity-modulated radiation therapy (IMRT) as first
      line treatment for these patients. Forty-one patients with pathologically
      confirmed NPC with distant metastasis at initial diagnosis seen between March
      2005 and February 2014 were included. All the patients were treated with platinum
      based systemic chemotherapy followed by definitive IMRT to the primary head and
      neck region with or without concurrent chemotherapy. In addition, local treatment
      to metastatic lesions was given in 19 patients. With a median follow-up time of
      25 months, 24 patients had died, and the estimated median overall survival time
      was 31.2 months. The 1-, 2-, 3- and 5-year estimated OS rates were 89.9, 67.4,
      41.1 and 22.5%, respectively. Prognostic analyses showed that serum lactate
      dehydrogenase level (P = 0.021) and number of metastatic sites (single vs.
      multiple; P = 0.016) were significant prognostic factors. Five patients are still
      alive without evidence of disease after 52 to >101 months. All of them had a
      single metastatic lesion and received local treatment to metastatic sites. These
      results suggest that the use of definitive IMRT to treat the locoregional tumor
      in combination with systemic chemotherapy may prolong survival in patients with
      newly diagnosed metastatic NPC, making curability a possible consideration in
      selected patients with single metastasis. Further prospective clinical trials are
      warranted.

PMID- 26219574
TI  - Wireless capsule endoscopy in adolescents with familial adenomatous polyposis.
AB  - AIMS AND BACKGROUND: Guidelines for surveillance in patients with familial
      adenomatous polyposis (FAP) recommend mutation carriers to undergo periodic
      colorectal examination starting in the early teens. Performing colonoscopy in
      children may lead to complications. Wireless capsule endoscopy (WCE) has been
      introduced recently to evaluate both the upper and lower gastrointestinal tract,
      and seems suitable as a first screening examination for adolescents. The aim of
      this study was to evaluate the pros and cons of WCE. METHODS: This was a
      retrospective review of a single institution database of adolescent patients with
      FAP identified through the Hereditary Colorectal Tumor Registry between 2007 and
      2013. The main outcomes were identification of upper and lower gastrointestinal
      tract polyps, tolerance of the examination, and number and size of polyps.
      RESULTS: Of 46 adolescent patients with FAP, 14 (30.4%) patients carrying
      adenomatous polyposis coli gene (APC) mutation, 6 male and 8 female, age (median,
      range) 12 (10-17) years, body mass index 19 (13-24), underwent WCE as first
      screening examination. The examination was completed in 13 patients (93.3%).
      Wireless capsule endoscopy identified the duodenal papilla in 4 patients and
      colonic and rectal polyps in all 13 patients. In 7 patients, fewer than 25 polyps
      were identified. No complications were recorded related to the use of the video
      capsule. CONCLUSIONS: Wireless capsule endoscopy is feasible and well-tolerated
      as a first screening examination in adolescent patients. It cannot be used as
      alternative to the colonoscopy, but could improve compliance with colonoscopy,
      and increase early adherence to a surveillance program.

PMID- 26219575
TI  - Altered structure and function of astrocytes following status epilepticus.
AB  - Temporal lobe epilepsy (TLE) is a devastating seizure disorder that is often
      caused by status epilepticus (SE). Temporal lobe epilepsy can be very difficult
      to control with currently available antiseizure drugs, and there are currently no
      disease-modifying therapies that can prevent the development of TLE in those
      patients who are at risk. While the functional changes that occur in neurons
      following SE and leading to TLE have been well studied, only recently has
      research attention turned to the role in epileptogenesis of astrocytes, the other
      major cell type of the brain. Given that epilepsy is a neural circuit disorder,
      innovative ways to evaluate the contributions that both neurons and astrocytes
      make to aberrant circuit activity will be critical for the understanding of the
      emergent network properties that result in seizures. Recently described
      approaches using genetically encoded calcium-indicating proteins can be used to
      image dynamic calcium transients, a marker of activity in both neurons and glial
      cells. It is anticipated that this work will lead to novel insights into the
      process of epileptogenesis at the network level and may identify disease
      modifying therapeutic targets that have been missed because of a largely
      neurocentric view of seizure generation following SE. This article is part of a
      Special Issue entitled "Status Epilepticus". 

PMID- 26219576
TI  - Associations among within-litter differences in early mothering received and
      later emotional behaviors, mothering, and cortical tryptophan hydroxylase-2
      expression in female laboratory rats.
AB  - This article is part of a Special Issue "Parental Care". The effects of
      differential maternal care received on offspring phenotype in rodents has been
      extensively studied between litters, but the consequences of differential
      mothering within litters on offspring neurobehavioral development have been
      rarely examined. We here investigated how variability in maternal care received
      among female rat siblings (measured four times daily on postnatal days 4, 6, 8,
      and 10) relates to the siblings' later emotional and maternal behaviors. As
      previously reported, we found that some female pups received up to three times
      more maternal licking bouts compared to their sisters; this difference was
      positively correlated with the pups' body weights. The number of maternal licking
      bouts that females received was negatively correlated with their later neophobic
      behaviors in an open field during periadolescence, but positively correlated with
      their anxiety-related behavior in an elevated plus maze during adulthood. Licking
      received was also positively correlated with females' later likelihood to
      retrieve pups in a maternal sensitization paradigm. In addition, females'
      neophobia during adolescence and anxiety-related behavior during adulthood
      predicted some aspects of both postpartum and sensitized maternal responsiveness.
      Medial prefrontal cortex expression of tryptophan hydroxylase-2 (TPH2; enzyme
      necessary for serotonin synthesis) was negatively associated with early maternal
      licking received. Interestingly, cortical TPH2 was positively associated with the
      maternal responsiveness of sensitized virgins but negatively associated with it
      in postpartum females. These results indicate that within-litter differences in
      maternal care received is an often neglected, but important, contributor to
      individual differences in offspring socioemotional behaviors as well as to the
      cortical serotonin neurochemistry that may influence these behaviors. 

PMID- 26219577
TI  - Pseudoprogression in a Patient With Glioblastoma Presenting as a Neurosurgical
      Emergency.

PMID- 26219578
TI  - The effects of folate intake on DNA and single-carbon pathway metabolism in the
      fruit fly Drosophila melanogaster compared to mammals.
AB  - Mechanisms of vitamin function in non-mammals are poorly understood, despite
      being essential for development. Folate and cobalamin are B-vitamin cofactors
      with overlapping roles in transferring various single-carbon units. In mammals,
      one or both is needed for nucleotide synthesis, DNA methylation, amino acid
      conversions and other reactions. However, there has been little investigation of
      the response to folate or cobalamin in insects. Here, we manipulated folate
      intake and potentially cobalamin levels in the fruit fly Drosophila melanogaster
      with chemically-defined diets, an antibiotic to reduce bacterially-derived
      vitamins, and the folate-interfering pharmaceutical methotrexate, to see if
      single-carbon metabolites and DNA synthesis rates would be affected. We found
      that similar to mammals with low folate intake, fruit fly larvae had
      significantly slower growth and DNA synthesis rates. But changes to single carbon
      metabolites did not mirror that of mammals with abnormal folate or given MTX.
      Five of the nine metabolites measured were not significantly affected
      (methionine, serine, glycine, methylglycine, and dimethylglycine) and three
      (cystathionine, methylgycine, and methylmalonic acid) were only decreased in
      larvae consuming methotrexate. Metabolites expected to be elevated if flies used
      cobalamin from microbial symbionts were not affected by dietary sulfaquinoxaline.
      Our data support the role of folate in nucleotide synthesis in D. melanogaster
      and that microbial symbionts provide functioning folates. We could not confirm
      how folate intake affects single carbon pathway metabolites, nor whether
      Drososphila use microbially-derived cobalamin. Further work should explore which
      cofactors are used in fruit flies in these important and potentially novel
      pathways. 

PMID- 26219579
TI  - Molecular characterization and organ-specific expression of the gene that encodes
      betaine aldehyde dehydrogenase from the white shrimp Litopenaeus vannamei in
      response to osmotic stress.
AB  - Crustaceans overcome osmotic disturbances by regulating their intracellular
      concentration of ions and osmolytes. Glycine betaine (GB), an osmolyte
      accumulated in response to hyperosmotic stress, is synthesized by betaine
      aldehyde dehydrogenase (BADH EC 1.2.1.8) through the oxidation of betaine
      aldehyde. A partial BADH cDNA sequence from the white shrimp Litopenaeus vannamei
      was obtained and its organ-specific expression during osmotic stress (low and
      high salinity) was evaluated. The partial BADH cDNA sequence (LvBADH) is 1103bp
      long and encodes an open reading frame for 217 protein residues. The amino acid
      sequence of LvBADH is related to that of other BADHs, TMABA-DH and ALDH9 from
      invertebrate and vertebrate homologues, and includes the essential domains of
      their function and regulation. LvBADH activity and mRNA expression were detected
      in the gills, hepatopancreas and muscle with the highest levels in the
      hepatopancreas. LvBADH mRNA expression increased 2-3-fold in the hepatopancreas
      and gills after 7days of osmotic variation (25 and 40ppt). In contrast, LvBADH
      mRNA expression in muscle decreased 4-fold and 15-fold after 7days at low and
      high salinity, respectively. The results indicate that LvBADH is ubiquitously
      expressed, but its levels are organ-specific and regulated by osmotic stress, and
      that LvBADH is involved in the cellular response of crustaceans to variations in
      environmental salinity. 

PMID- 26219580
TI  - Molecular cloning, characterization, and expression analysis of a gonadotropin
      releasing hormone-like cDNA in the clam, Ruditapes philippinarum.
AB  - Gonadotropin-releasing hormone (GnRH) is a key neuropeptide regulating
      reproduction in vertebrates. In the present study, we have cloned and identified
      the cDNA sequence of the prepro-GnRH (rp-GnRH) in the Manila clam Ruditapes
      philippinarum. The open reading frame encodes a protein of 94 amino acids, which
      consists of a signal peptide, a GnRH dodecapeptide, a cleavage site, and a GnRH
      associated peptide. These deduced peptides were highly homologous to that
      reported for other molluscs. We used temperature control to promote gonadal
      development of the clams. The mRNA expression of rp-GnRH in the visceral ganglia
      from clams at different reproductive stages was determined by quantitative RT
      PCR. The levels of steroids progesterone (P), testosterone (T), and estradiol
      17beta (E2) in the hemolymph of the corresponding clam were measured by ELISA.
      The rp-GnRH mRNA was highly expressed at the gonadal early development stage.
      Concentrations of P, T, and E2 also increased at the early development stage in
      both sexes. Positive significant correlations between rp-GnRH expression and P
      content as well as between rp-GnRH expression and T content were observed
      throughout the gonadal maturation. The results from this study may help to better
      understand the physiological functions of the native forms of GnRH-like peptides
      and the actions of GnRH on sex steroids release in bivalve molluscs. 

PMID- 26219581
TI  - Muscle satellite cells increase during hibernation in ground squirrels.
AB  - Skeletal muscle satellite cells (SCs) are involved in muscle growth and repair.
      However, clarification of their behavior in hibernating mammals is lacking. The
      aim of this study was to quantify SCs and total myonuclei in hibernator muscle
      during different phases of the torpor-arousal cycle. Skeletal muscle was
      collected from thirteen-lined ground squirrels, Ictidomys tridecemlineatus, at
      five timepoints during hibernation: control euthermic [CON, stable body
      temperature (Tb)], early torpor (ET, within 24h), late torpor (LT, 5+ consecutive
      days), early arousal (EA, increased respiratory rate >60 breaths/min, Tb 9-12
      degrees C) and interbout arousal (IA, euthermic Tb). Protein levels of p21, Myf5,
      Wnt4, and beta-catenin were determined by western blotting. SCs (Pax7(+)) and
      myonuclei were identified using immunohistochemistry. Over the torpor-arousal
      cycle, myonuclei/fiber remained unchanged. However, the percentage of SCs
      increased significantly during ET (7.35+/-1.04% vs. CONTROL: 4.18+/-0.58%;
      p<0.05) and returned to control levels during LT. This coincided with a 224%
      increase in p21 protein during ET. Protein levels of Wnt4 did not change
      throughout, whereas Myf5 was lower during EA (p<0.08) and IA (p<0.05). Compared
      to torpor, beta-catenin increased by 247% and 279% during EA and IA, respectively
      (p<0.05). In conclusion, SCs were not dormant during hibernation and increased
      numbers of SC during ET corresponded with elevated amounts of p21 suggesting that
      cell cycle control may explain the SC return to baseline levels during late
      torpor. Despite relatively low Tb during early arousal, active control of
      quiescence by Myf5 is reduced.

PMID- 26219582
TI  - Olfactory Receptor Subgenomes Linked with Broad Ecological Adaptations in
      Sauropsida.
AB  - Olfactory receptors (ORs) govern a prime sensory function. Extant birds have
      distinct olfactory abilities, but the molecular mechanisms underlining
      diversification and specialization remain mostly unknown. We explored OR
      diversity in 48 phylogenetic and ecologically diverse birds and 2 reptiles
      (alligator and green sea turtle). OR subgenomes showed species- and lineage
      specific variation related with ecological requirements. Overall 1,953 OR genes
      were identified in reptiles and 16,503 in birds. The two reptiles had larger OR
      gene repertoires (989 and 964 genes, respectively) than birds (182-688 genes).
      Overall, birds had more pseudogenes (7,855) than intact genes (1,944). The
      alligator had significantly more functional genes than sea turtle, likely because
      of distinct foraging habits. We found rapid species-specific expansion and
      positive selection in OR14 (detects hydrophobic compounds) in birds and in OR51
      and OR52 (detect hydrophilic compounds) in sea turtle, suggestive of terrestrial
      and aquatic adaptations, respectively. Ecological partitioning among birds of
      prey, water birds, land birds, and vocal learners showed that diverse ecological
      factors determined olfactory ability and influenced corresponding olfactory
      receptor subgenome. OR5/8/9 was expanded in predatory birds and alligator,
      suggesting adaptive specialization for carnivory. OR families 2/13, 51, and 52
      were correlated with aquatic adaptations (water birds), OR families 6 and 10 were
      more pronounced in vocal-learning birds, whereas most specialized land birds had
      an expanded OR family 14. Olfactory bulb ratio (OBR) and OR gene repertoire were
      correlated. Birds that forage for prey (carnivores/piscivores) had relatively
      complex OBR and OR gene repertoires compared with modern birds, including
      passerines, perhaps due to highly developed cognitive capacities facilitating
      foraging innovations. 

PMID- 26219583
TI  - Divergence in Enzymatic Activities in the Soybean GST Supergene Family Provides
      New Insight into the Evolutionary Dynamics of Whole-Genome Duplicates.
AB  - Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome
      evolution. A duplicate of all genes is present in the genome immediately
      following a WGD event. However, the evolutionary mechanisms responsible for the
      loss of, or retention and subsequent functional divergence of polyploidy-derived
      duplicates remain largely unknown. In this study we reconstructed the
      evolutionary history of the glutathione S-transferase (GST) gene family from the
      soybean genome, and identified 72 GST duplicated gene pairs formed by a recent
      Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of
      duplicated GST gene pairs experienced gene losses or pseudogenization, whereas
      28% of GST gene pairs have been retained in the soybean genome. The GST
      pseudogenes were under relaxed selective constraints, whereas functional GSTs
      were subject to strong purifying selection. Plant GST genes play important roles
      in stress tolerance and detoxification metabolism. By examining the gene
      expression responses to abiotic stresses and enzymatic properties of the
      ancestral and current proteins, we found that polyploidy-derived GST duplicates
      show the divergence in enzymatic activities. Through site-directed mutagenesis of
      ancestral proteins, this study revealed that nonsynonymous substitutions of key
      amino acid sites play an important role in the divergence of enzymatic functions
      of polyploidy-derived GST duplicates. These findings provide new insights into
      the evolutionary and functional dynamics of polyploidy-derived duplicate genes. 

PMID- 26219584
TI  - Renal impairment in different phenotypes of Wilson disease.
AB  - Wilson's disease (WD) is a rare autosomal recessive genetic disease resulting in
      the chronic deposition of copper in both liver and brain. This can lead to
      hepatic, neurologic, and psychiatric manifestations. Renal impairment can occur
      in any period of WD, but the mechanism is not yet known. In this study, we
      analyzed the clinical data of 691 newly diagnosed WD patients to investigate the
      blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) levels in
      different subtypes of WD. This study included 691 newly diagnosed WD patients, 34
      asymptomatic cases, and 127 healthy controls. The entire sample was assessed for
      serum levels of BUN, Cr, and UA. We found that the levels of BUN and Cr in WD
      patients who had neurological manifestations were higher (p < 0.001). In
      contrast, those patients presenting with a combined neurological and hepatic
      condition showed the lowest serum levels of UA (p = 0.026). There are differences
      in renal impairment between the endo-phenotypes of WD. Renal impairment can
      reflect differential copper deposition in organs other than the liver. 

PMID- 26219585
TI  - Hypobaric hypoxia is not a direct dyspnogenic factor in healthy individuals at
      rest.
AB  - Dyspnea consists of various uncomfortable respiratory sensations. It is believed
      that hypoxia causes dyspnea, but whether hypoxia is a direct dyspnogenic factor
      remains uncertain. We investigated whether hypoxia has a direct dyspnogenic
      effect. We evaluated changes in vital signs, arterial blood gases, SaO2, CaO2,
      Borg scale, and Mini-Mental State Examination in seven mountain climbers by using
      a hypobaric hypoxic chamber in which the barometric pressure was lowered to the
      simulated altitude of 4500 m. PaO2 and CaO2 both decreased significantly as the
      simulated altitude increased. On the other hand, Borg scale score which reflects
      dyspnea showed no significant difference. At the simulated altitude of 4500 m,
      Borg scale score was 1.5 +/- 1.2 (mean +/- SD), despite the presence of absolute
      hypoxia (PaO2, 46.8 +/- 8.3T; CaO2, 16.4 +/- 0.6 mL/dL). These results suggest
      that hypoxia is not a direct dyspnogenic factor in healthy individuals capable of
      breathing without restriction at rest.

PMID- 26219586
TI  - Assessment of D-methionine protecting cisplatin-induced otolith toxicity by
      vestibular-evoked myogenic potential tests, ATPase activities and oxidative state
      in guinea pigs.
AB  - To date, inadequate study has been devoted to the toxic vestibular effects caused
      by cisplatin. In addition, no electrophysiological examination has been conducted
      to assess cisplatin-induced otolith toxicity. The purposes of this study are thus
      two-fold: 1) to determine whether cervical vestibular-evoked myogenic potentials
      (VEMPs) and ocular VEMPs are practical electrophysiological methods of testing
      for cisplatin-induced otolith toxicity and 2) to examine if D-methionine (D-met)
      pre-injection would protect the otolith organs against cisplatin-induced changes
      in enzyme activities and/or oxidative status. Guinea pigs were intraperitoneally
      treated once daily with the following injections for seven consecutive days:
      sterile 0.9% saline control, cisplatin (5 mg/kg) only, D-met (300 mg/kg) only, or
      a combination of d-met (300 mg/kg) and cisplatin (5 mg/kg), respectively, with a
      30 minute window in between. Each animal underwent the oVEMP and cVEMP tests
      before and after treatment. The changes in the biochemistry of the otolith
      organs, including membranous Na(+), K(+)-ATPase and Ca(2+)-ATPase, lipid
      peroxidation (LPO) levels and nitric oxide (NO) levels, were also evaluated. In
      the cisplatin-only treated guinea pigs, the mean amplitudes of the oVEMP tests
      were significantly (p<0.05) decreased when compared to the other three groups. In
      guinea pigs receiving both D-met and cisplatin, the amplitudes of their oVEMP
      tests were significantly larger (p<0.05) than those of the cisplatin-only group,
      but smaller (p<0.05) than those of the saline control or D-met-only group.
      However, no significant difference of the amplitudes of cVEMP tests was noted
      among the four groups. In comparison with the other three groups, the cisplatin
      only group had the lowest (ps<0.05) mean Na(+), K(+)-ATPase and Ca(2+)-ATPase,
      and the highest (ps<0.05) LPO and NO levels. The oVEMP tests were feasible for
      the evaluation of cisplatin-related otolith dysfunction. D-Met attenuated the
      reduced ATPase activities and increased oxidative stress induced by cisplatin
      toxicity in the otolith organs.

PMID- 26219587
TI  - Thermochemical treatment of sewage sludge ash with sodium salt additives for
      phosphorus fertilizer production--Analysis of underlying chemical reactions.
AB  - Stocks of high grade phosphate rock are becoming scarce, and there is growing
      concern about potentially harmful impurities in conventional phosphorus
      fertilizers. Sewage sludge ash is a promising secondary phosphorus source.
      However, to remove heavy metals and convert the phosphorus contained in sewage
      sludge ash into mineral phases available to plants, an after-treatment is
      required. Laboratory-scale calcination experiments of sewage sludge ash blended
      with sodium salts using dried sewage sludge as a reducing agent were carried out
      at 1000 degrees C. Thus, the Ca3(PO4)2 or whitlockite component of raw sewage
      sludge ash, which is not readily plant available, was converted to CaNaPO4
      (buchwaldite). Consequently, nearly complete phosphorus solubility in ammonium
      citrate (a well-established indicator for plant availability) was achieved.
      Moreover, it was shown that Na2CO3 may be replaced by moderately priced Na2SO4.
      However, molar ratios of Na/P>2 were required to achieve >80% phosphorus
      solubility. Such over-stoichiometric Na consumption is largely caused by side
      reactions with the SiO2 component of the sewage sludge ash - an explanation for
      which clear evidence is provided for the first time. 

PMID- 26219588
TI  - Cardiac critical care: Surgical trainees want and need expertise.

PMID- 26219589
TI  - Acute type A aortic dissection 101.

PMID- 26219590
TI  - Hemofiltration in ex vivo lung perfusion-a study in experimentally induced
      pulmonary edema.
AB  - OBJECTIVES: Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema.
      In a pig model with induced pulmonary edema, we evaluated the effect of
      hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and
      lung weight. METHODS: In anesthetized pigs (n = 14), pulmonary edema was induced
      by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg),
      for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to
      EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for
      each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%.
      Oncotic pressure, lung performance, and weight were measured before and after 180
      minutes of EVLP reconditioning with or without HF. RESULTS: After in vivo
      induction of edema, arterial oxygen tension (Pao2)/inspired oxygen fraction
      (Fio2), and compliance decreased by 63% and 16%, respectively. Pao2/Fio2 was
      considerably improved at first evaluation ex vivo in both groups. HF increased
      oncotic pressure by 43% and decreased lung weight by 15%. The effects were
      negligible in the noHF group. Compliance decreased in both groups during
      reconditioning, although less so in the HF group (P < .05). Pao2/Fio2, shunt
      fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow
      index decreased in both groups, and was partially reversed by nitroglycerin.
      Dorsal atelectatic consolidations were seen in both groups. CONCLUSIONS: In this
      lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect
      the degree of lung edema. HF during EVLP increased perfusate oncotic pressure,
      decreased lung weight with beneficial effects on compliance, but did not improve
      lung oxygenation capacity.

PMID- 26219591
TI  - An MTCH2 pathway repressing mitochondria metabolism regulates haematopoietic stem
      cell fate.
AB  - The metabolic state of stem cells is emerging as an important determinant of
      their fate. In the bone marrow, haematopoietic stem cell (HSC) entry into cycle,
      triggered by an increase in intracellular reactive oxygen species (ROS),
      corresponds to a critical metabolic switch from glycolysis to mitochondrial
      oxidative phosphorylation (OXPHOS). Here we show that loss of mitochondrial
      carrier homologue 2 (MTCH2) increases mitochondrial OXPHOS, triggering HSC and
      progenitor entry into cycle. Elevated OXPHOS is accompanied by an increase in
      mitochondrial size, increase in ATP and ROS levels, and protection from
      irradiation-induced apoptosis. In contrast, a phosphorylation-deficient mutant of
      BID, MTCH2's ligand, induces a similar increase in OXPHOS, but with higher ROS
      and reduced ATP levels, and is associated with hypersensitivity to irradiation.
      Thus, our results demonstrate that MTCH2 is a negative regulator of mitochondrial
      OXPHOS downstream of BID, indispensible in maintaining HSC homeostasis. 

PMID- 26219592
TI  - Advanced imaging of the scapholunate ligamentous complex.
AB  - The scapholunate joint is one of the most involved in wrist injuries. Its
      stability depends on primary and secondary stabilisers forming together the
      scapholunate complex. This ligamentous complex is often evaluated by wrist
      arthroscopy. To avoid surgery as diagnostic procedure, optimization of MR imaging
      parameters as use of three-dimensional (3D) sequences with very thin slices and
      high spatial resolution, is needed to detect lesions of the intrinsic and
      extrinsic ligaments of the scapholunate complex. The paper reviews the literature
      on imaging of radial-sided carpal ligaments with advanced computed tomographic
      arthrography (CTA) and magnetic resonance arthrography (MRA) to evaluate the
      scapholunate complex. Anatomy and pathology of the ligamentous complex are
      described and illustrated with CTA, MRA and corresponding arthroscopy. Sprains,
      mid-substance tears, avulsions and fibrous infiltrations of carpal ligaments
      could be identified on CTA and MRA images using 3D fat-saturated PD and 3D DESS
      (dual echo with steady-state precession) sequences with 0.5-mm-thick slices.
      Imaging signs of scapholunate complex pathology include: discontinuity,
      nonvisualization, changes in signal intensity, contrast extravasation (MRA),
      contour irregularity and waviness and periligamentous infiltration by edema,
      granulation tissue or fibrosis. Based on this preliminary experience, we believe
      that 3 T MRA using 3D sequences with 0.5-mm-thick slices and multiplanar
      reconstructions is capable to evaluate the scapholunate complex and could help to
      reduce the number of diagnostic arthroscopies. 

PMID- 26219593
TI  - Assessing cerebral glucose metabolism in patients with idiopathic rapid eye
      movement sleep behavior disorder.
AB  - Idiopathic rapid eye movement sleep behavior disorder (RBD) is a risk marker for
      subsequent development of neurodegenerative parkinsonism. In this study, we aimed
      to investigate whether regional cerebral metabolism is altered in patients with
      RBD and whether regional metabolic activities are associated with clinical
      measurements in individual patients. Twenty-one patients with polysomnogram
      confirmed RBD and 21 age-matched healthy controls were recruited to undertake
      positron emission tomography imaging with [(18)F]fluorodeoxyglucose. Differences
      in normalized regional metabolism and correlations between metabolic activity and
      clinical indices in RBD patients were evaluated on a voxel basis using statistic
      parametric mapping analysis. Compared with controls, patients with RBD showed
      increased metabolism in the hippocampus/parahippocampus, cingulate, supplementary
      motor area, and pons, but decreased metabolism in the occipital cortex/lingual
      gyrus (P<0.001). RBD duration correlated with metabolism positively in the
      anterior vermis (r=0.55, P=0.01), but negatively in the medial frontal gyrus (r=
      0.59, P=0.005). In addition, chin electromyographic activity presented a positive
      metabolic correlation in the hippocampus/parahippocampus (r=0.48, P=0.02), but a
      negative metabolic correlation in the posterior cingulate (r=-0.61, P=0.002).
      This study has suggested that region-specific metabolic abnormalities exist in
      RBD patients and regional metabolic activities are associated with clinical
      measures such as RBD duration and chin electromyographic activity. 

PMID- 26219594
TI  - A novel SPECT-based approach reveals early mechanisms of central and peripheral
      inflammation after cerebral ischemia.
AB  - Inflammation that develops in the brain and peripheral organs after stroke
      contributes profoundly to poor outcome of patients. However, mechanisms through
      which inflammation impacts on brain injury and overall outcome are improperly
      understood, in part because the earliest inflammatory events after brain injury
      are not revealed by current imaging tools. Here, we show that single-photon
      emission computed tomography (NanoSPECT/CT Plus) allows visualization of blood
      brain barrier (BBB) injury after experimental stroke well before changes can be
      detected with magnetic resonance imaging (MRI). Early 99mTc-DTPA (diethylene
      triamine pentaacetic acid) signal changes predict infarct development and
      systemic inflammation preceding experimental stroke leads to very early perfusion
      deficits and increased BBB injury within 2 hours after the onset of ischemia.
      Acute brain injury also leads to peripheral inflammation and immunosuppression,
      which contribute to poor outcome of stroke patients. The SPECT imaging revealed
      early (within 2 hours) changes in perfusion, barrier function and inflammation in
      the lungs and the gut after experimental stroke, with good predictive value for
      the development of histopathologic changes at later time points. Collectively,
      visualization of early inflammatory changes after stroke could open new
      translational research avenues to elucidate the interactions between central and
      peripheral inflammation and to evaluate in vivo 'multi-system' effects of
      putative anti-inflammatory treatments. 

PMID- 26219595
TI  - Alzheimer's disease--subcortical vascular disease spectrum in a hospital-based
      setting: Overview of results from the Gothenburg MCI and dementia studies.
AB  - The ability to discriminate between Alzheimer's disease (AD), subcortical
      vascular disease, and other cognitive disorders is crucial for diagnostic
      purposes and clinical trial outcomes. Patients with primarily subcortical
      vascular disease are unlikely to benefit from treatments targeting the AD
      pathogenic mechanisms and vice versa. The Gothenburg mild cognitive impairment
      (MCI) and dementia studies are prospective, observational, single-center cohort
      studies suitable for both cross-sectional and longitudinal analysis that outline
      the cognitive profiles and biomarker characteristics of patients with AD,
      subcortical vascular disease, and other cognitive disorders. The studies, the
      first of which started in 1987, comprise inpatients with manifest dementia and
      patients seeking care for cognitive disorders at an outpatient memory clinic.
      This article gives an overview of the major published papers (neuropsychological,
      imaging/physiology, and neurochemical) of the studies including the ongoing
      Gothenburg MCI study. The main findings suggest that subcortical vascular disease
      with or without dementia exhibit a characteristic neuropsychological pattern of
      mental slowness and executive dysfunction and neurochemical deviations typical of
      white matter changes and disturbed blood-brain barrier function. Our findings may
      contribute to better healthcare for this underrecognized group of patients. The
      Gothenburg MCI study has also published papers on multimodal prediction of
      dementia, and cognitive reserve.

PMID- 26219596
TI  - Recombinant tissue-type plasminogen activator transiently enhances blood-brain
      barrier permeability during cerebral ischemia through vascular endothelial growth
      factor-mediated endothelial endocytosis in mice.
AB  - Recombinant tissue-type plasminogen activator (rt-PA) modulates cerebrovascular
      permeability and exacerbates brain injury in ischemic stroke, but its mechanisms
      remain unclear. We studied the involvement of vascular endothelial growth factor
      (VEGF)-mediated endocytosis in the increase of blood-brain barrier (BBB)
      permeability potentiated by rt-PA after ischemic stroke. The rt-PA treatment at 4
      hours after middle cerebral artery occlusion induced a transient increase in BBB
      permeability after ischemic stroke in mice, which was suppressed by antagonists
      of either low-density lipoprotein receptor families (LDLRs) or VEGF receptor-2
      (VEGFR-2). In immortalized bEnd.3 endothelial cells, rt-PA treatment upregulated
      VEGF expression and VEGFR-2 phosphorylation under ischemic conditions in an LDLR
      dependent manner. In addition, rt-PA treatment increased endocytosis and
      transcellular transport in bEnd.3 monolayers under ischemic conditions, which
      were suppressed by the inhibition of LDLRs, VEGF, or VEGFR-2. The rt-PA treatment
      also increased the endocytosis of endothelial cells in the ischemic brain region
      after stroke in mice. These findings indicate that rt-PA increased BBB
      permeability via induction of VEGF, which at least partially mediates subsequent
      increase in endothelial endocytosis. Therefore, inhibition of VEGF induction may
      have beneficial effects after thrombolytic therapy with rt-PA treatment after
      stroke. 

PMID- 26219597
TI  - Impaired vascular remodeling after endothelial progenitor cell transplantation in
      MMP9-deficient mice suffering cortical cerebral ischemia.
AB  - Endothelial progenitor cells (EPCs) are being investigated for advanced
      therapies, and matrix metalloproteinase 9 (MMP9) has an important role in stroke
      recovery. Our aim was to determine whether tissue MMP9 influences the EPC-induced
      angiogenesis after ischemia. Wild-type (WT) and MMP9-deficient mice (MMP9/KO)
      were subjected to cerebral ischemia and treated with vehicle or outgrowth EPCs.
      After 3 weeks, we observed an increase in the peri-infarct vessel density in WT
      animals but not in MMP9/KO mice; no differences were found in the vehicle-treated
      groups. Our data suggest that tissue MMP9 has a crucial role in EPC-induced
      vascular remodeling after stroke. 

PMID- 26219599
TI  - The Journal of Cerebral Blood Flow and  Metabolism clinical, inaugural issue.

PMID- 26219598
TI  - Knockout of silent information regulator 2 (SIRT2) preserves neurological
      function after experimental stroke in mice.
AB  - Sirtuin-2 (Sirt2) is a member of the NAD(+)-dependent protein deacetylase family.
      Various members of the sirtuin class have been found to be involved in processes
      related to longevity, regulation of inflammation, and neuroprotection. Induction
      of Sirt2 mRNA was found in the whole hemisphere after experimental stroke in a
      recent screening approach. Moreover, Sirt2 protein is highly expressed in myelin
      rich brain regions after stroke. To examine the effects of Sirt2 on ischemic
      stroke, we induced transient focal cerebral ischemia in adult male Sirt2-knockout
      and wild-type mice. Two stroke models with different occlusion times were
      applied: a severe ischemia (45 minutes of middle cerebral artery occlusion
      (MCAO)) and a mild one (15 minutes of MCAO), which was used to focus on
      subcortical infarcts. Neurological deficit was determined at 48 hours after 45
      minutes of MCAO, and up to 7 days after induction of 15 minutes of cerebral
      ischemia. In contrast to recent data on Sirt1, Sirt2(-/-) mice showed less
      neurological deficits in both models of experimental stroke, with the strongest
      manifestation after 48 hours of reperfusion. However, we did not observe a
      significant difference of stroke volumes or inflammatory cell count between Sirt2
      deficient and wild-type mice. Thus we postulate that Sirt2 mediates myelin
      dependent neuronal dysfunction during the early phase after ischemic stroke. 

PMID- 26219600
TI  - The indirect NMDAR antagonist acamprosate induces postischemic neurologic
      recovery associated with sustained neuroprotection and neuroregeneration.
AB  - Cerebral ischemia stimulates N-methyl-d-aspartate receptors (NMDARs) resulting in
      increased calcium concentration and excitotoxicity. Yet, deactivation of NMDAR
      failed in clinical studies due to poor preclinical study designs or toxicity of
      NMDAR antagonists. Acamprosate is an indirect NMDAR antagonist used for patients
      with chronic alcohol dependence. We herein analyzed the therapeutic potential of
      acamprosate on brain injury, neurologic recovery and their underlying mechanisms.
      Mice were exposed to cerebral ischemia, treated with intraperitoneal injections
      of acamprosate or saline (controls), and allowed to survive until 3 months.
      Acamprosate yielded sustained neuroprotection and increased neurologic recovery
      when given no later than 12 hours after stroke. The latter was associated with
      increased postischemic angioneurogenesis, albeit acamprosate did not stimulate
      angioneurogenesis itself. Rather, increased angioneurogenesis was due to
      inhibition of calpain-mediated pro-injurious signaling cascades. As such,
      acamprosate-mediated reduction of calpain activity resulted in decreased
      degradation of p35, increased abundance of the pro-survival factor STAT6, and
      reduced N-terminal-Jun-kinase activation. Inhibition of calpain was associated
      with enhanced stability of the blood-brain barrier, reduction of oxidative stress
      and cerebral leukocyte infiltration. Taken into account its excellent
      tolerability, its sustained effects on neurologic recovery, brain tissue
      survival, and neural remodeling, acamprosate is an intriguing candidate for
      adjuvant future stroke treatment. 

PMID- 26219601
TI  - Deficient inhibitory processing in trait anxiety: Evidence from context-dependent
      fear learning, extinction recall and renewal.
AB  - BACKGROUND: Impaired fear inhibition has been described as a hallmark of
      pathological anxiety. We aimed at further characterizing the relation between
      fear inhibition and anxiety by extending previous work to contextual safety
      stimuli as well as to dimensional scores of trait anxiety in a large sample.
      METHODS: We employed a validated paradigm for context-dependent fear
      acquisition/extinction (day 1) and retrieval/expression (day 2) in 377 healthy
      individuals. This large sample size allowed the employment of a dimensional
      rather than binary approach with respect to individual differences in trait
      anxiety. RESULTS: We observed a positive correlation on day 1 between trait
      anxiety with all CSs that possess an inherent inhibitory component, conveyed
      either by reliable non-reinforcement of a specific CS in a dangerous context
      (safe cue) or by the context itself (i.e., safe context). No correlation however
      was observed for a CS that possesses excitatory (threatening) properties only.
      These results were observed during fear learning (day 1) for US expectancy and
      fear ratings but not for SCRs. No such pattern was evident during fear and
      extinction retrieval/expression (day 2). CONCLUSION: We provide further evidence
      that high trait anxiety is associated with the inability to take immediate
      advantage of environmental safety cues (cued and contextual), which might
      represent a promising trans-diagnostic marker for different anxiety disorders.
      Consequently, the incorporation of methods to optimize inhibitory learning in
      current cognitive behavioral therapy (CBT) treatments might open up a promising
      avenue for precision medicine in anxiety disorders. LIMITATIONS: We did not
      include patients diagnosed with anxiety disorders.

PMID- 26219602
TI  - Brain volumetry and self-regulation of brain activity relevant for neurofeedback.
AB  - Neurofeedback is a technique to learn to control brain signals by means of real
      time feedback. In the present study, the individual ability to learn two EEG
      neurofeedback protocols - sensorimotor rhythm and gamma rhythm - was related to
      structural properties of the brain. The volumes in the anterior insula
      bilaterally, left thalamus, right frontal operculum, right putamen, right middle
      frontal gyrus, and right lingual gyrus predicted the outcomes of sensorimotor
      rhythm training. Gray matter volumes in the supplementary motor area and left
      middle frontal gyrus predicted the outcomes of gamma rhythm training. These
      findings combined with further evidence from the literature are compatible with
      the existence of a more general self-control network, which through self
      referential and self-control processes regulates neurofeedback learning. 

PMID- 26219603
TI  - REM sleep and emotional face memory in typically-developing children and children
      with autism.
AB  - Relationship between REM sleep and memory was assessed in 13 neurotypical and 13
      children with Autistic Spectrum Disorder (ASD). A neutral/positive/negative face
      recognition task was administered the evening before (learning and immediate
      recognition) and the morning after (delayed recognition) sleep. The number of
      rapid eye movements (REMs), beta and theta EEG activity over the visual areas
      were measured during REM sleep. Compared to neurotypical children, children with
      ASD showed more theta activity and longer reaction time (RT) for correct
      responses in delayed recognition of neutral faces. Both groups showed a positive
      correlation between sleep and performance but different patterns emerged: in
      neurotypical children, accuracy for recalling neutral faces and overall RT
      improvement overnight was correlated with EEG activity and REMs; in children with
      ASD, overnight RT improvement for positive and negative faces correlated with
      theta and beta activity, respectively. These results suggest that neurotypical
      and children with ASD use different sleep-related brain networks to process
      faces. 

PMID- 26219604
TI  - Neuronal Representation of Ultraviolet Visual Stimuli in Mouse Primary Visual
      Cortex.
AB  - The mouse has become an important model for understanding the neural basis of
      visual perception. Although it has long been known that mouse lens transmits
      ultraviolet (UV) light and mouse opsins have absorption in the UV band, little is
      known about how UV visual information is processed in the mouse brain. Using a
      custom UV stimulation system and in vivo calcium imaging, we characterized the
      feature selectivity of layer 2/3 neurons in mouse primary visual cortex (V1). In
      adult mice, a comparable percentage of the neuronal population responds to UV and
      visible stimuli, with similar pattern selectivity and receptive field properties.
      In young mice, the orientation selectivity for UV stimuli increased steadily
      during development, but not direction selectivity. Our results suggest that, by
      expanding the spectral window through which the mouse can acquire visual
      information, UV sensitivity provides an important component for mouse vision. 

PMID- 26219605
TI  - An observation-based progression modeling approach to spring and autumn deciduous
      tree phenology.
AB  - It is important to accurately determine the response of spring and autumn
      phenology to climate change in forest ecosystems, as phenological variations
      affect carbon balance, forest productivity, and biodiversity. We observed
      phenology intensively throughout spring and autumn in a temperate deciduous
      woodlot at Milwaukee, WI, USA, during 2007-2012. Twenty-four phenophase levels in
      spring and eight in autumn were recorded for 106 trees, including white ash,
      basswood, white oak, boxelder, red oak, and hophornbeam. Our phenological
      progression models revealed that accumulated degree-days and day length explained
      87.9-93.4 % of the variation in spring canopy development and 75.8-89.1 % of the
      variation in autumn senescence. In addition, the timing of community-level spring
      and autumn phenophases and the length of the growing season from 1871 to 2012
      were reconstructed with the models developed. All simulated spring phenophases
      significantly advanced at a rate from 0.24 to 0.48 days/decade (p <= 0.001)
      during the 1871-2012 period and from 1.58 to 2.00 days/decade (p < 0.02) during
      the 1970-2012 period; two simulated autumn phenophases were significantly delayed
      at a rate of 0.37 (mid-leaf coloration) and 0.50 (full-leaf coloration)
      days/decade (p < 0.01) during the 1970-2012 period. Consequently, the simulated
      growing season lengthened at a rate of 0.45 and 2.50 days/decade (p < =0.001),
      respectively, during the two periods. Our results further showed the variability
      of responses to climate between early and late spring phenophases, as well as
      between leaf coloration and leaf fall, and suggested accelerating simulated
      ecosystem responses to climate warming over the last four decades in comparison
      to the past 142 years. 

PMID- 26219606
TI  - Implications of climatic seasonality on activity patterns and resource use by
      sympatric peccaries in northern Pantanal.
AB  - We evaluated the effects of climate seasonality from a thermal and water
      availability perspective on the activity patterns and resource use of Pecari
      tajacu and Tayassu pecari during wet and dry seasons in the northeastern
      Brazilian Pantanal. We used camera traps and temperature sensors to record
      species activity patterns in relation to temperature, established five habitat
      categories based on flooding intensity and local vegetation characteristics,
      assessed the activity patterns of each species in dry and wet periods and in
      artificial water bodies using circular statistical metrics, and calculated niche
      amplitude and overlap on three axes (temperature, time, and habitat) in both
      periods. Peccaries shared a strong resemblance in resource use and in their
      responses to seasonal variations in the tested gradients. The activity patterns
      of both species exhibited a significant correlation with air temperature on all
      the evaluated measures, and both species strongly reduced their activity when the
      air temperature exceeded 35  degrees C. High temperatures associated with low
      water availability were most likely responsible for the changes in species
      activity patterns, which resulted in an increased temporal overlap in habitat use
      throughout the dry season. However, the peccaries avoided intensively flooded
      habitats; therefore, the habitat gradient overlap was greater during the wet
      period. Our results show that an increase in niche overlap on the environmental
      gradient as a result of climatic seasonality may be partially compensated by a
      reduction in other niche dimensions. In this case, temporal partitioning appears
      to be an important, viable mechanism to reduce competition by potentially
      competing species. 

PMID- 26219608
TI  - The value of primary tumor (18)F-FDG uptake on preoperative PET/CT for predicting
      intratumoral lymphatic invasion and axillary nodal metastasis.
AB  - BACKGROUND: The preoperative evaluation of axillary lymph node (LN) status is
      important for prognostic prediction of breast cancer. We investigated the ability
      of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography
      ((18)F-FDG PET/CT) to predict intratumoral lymphatic invasion and axillary LN
      metastasis. METHODS: The preoperative (18)F-FDG PET/CT images and pathologic
      reports for 428 breast cancer patients between January 2003 and December 2008
      were evaluated retrospectively. The maximum standardized uptake value (SUVmax) of
      the primary tumor on (18)F-FDG PET/CT, the degree of lymphatic invasion, and
      axillary LN metastasis identified by pathologic reports were assessed. Univariate
      and multivariate logistic regression analyses were performed to identify the
      significant features of the primary tumor that were associated with
      pathologically confirmed axillary LN metastasis. RESULTS: The mean SUVmax of
      primary tumors with lymphatic invasion was higher than that of tumors without
      lymphatic invasion (5.13 +/- 3.49 vs. 3.00 +/- 2.47; p < 0.0001). The mean SUVmax
      of primary tumors with pathologically confirmed axillary LN metastasis was higher
      than that of tumors without LN metastasis (4.93 +/- 3.32 vs. 3.22 +/- 2.78; p <
      0.0001). The degree of lymphatic invasion correlated strongly with axillary LN
      metastasis (p = 0.0001). Multiple logistic regression analysis showed that the
      high SUVmax of the primary tumor (>2.8), the high SUVmax of the axillary LN
      (>0.72) and the degree of lymphatic invasion were significant predictive factors
      of the development of axillary LN metastasis. CONCLUSION: Breast cancer patients
      with higher primary tumor (18)F-FDG uptake are at higher risk of concurrent
      intratumoral lymphatic invasion and axillary LN metastasis.

PMID- 26219607
TI  - Opportunities and constraints of presently used thermal manikins for thermo
      physiological simulation of the human body.
AB  - Combining the strengths of an advanced mathematical model of human physiology and
      a thermal manikin is a new paradigm for simulating thermal behaviour of humans.
      However, the forerunners of such adaptive manikins showed some substantial
      limitations. This project aimed to determine the opportunities and constraints of
      the existing thermal manikins when dynamically controlled by a mathematical model
      of human thermal physiology. Four thermal manikins were selected and evaluated
      for their heat flux measurement uncertainty including lateral heat flows between
      manikin body parts and the response of each sector to the frequent change of the
      set-point temperature typical when using a physiological model for control. In
      general, all evaluated manikins are suitable for coupling with a physiological
      model with some recommendations for further improvement of manikin dynamic
      performance. The proposed methodology is useful to improve the performance of the
      adaptive manikins and help to provide a reliable and versatile tool for the broad
      research and development domain of clothing, automotive and building engineering.

PMID- 26219609
TI  - Are There Linguistic Markers of Suicidal Writing That Can Predict the Course of
      Treatment? A Repeated Measures Longitudinal Analysis.
AB  - The purpose of this pilot study was to predict resolution of suicidal ideation
      and risk over the course of therapy among suicidal outpatients (N = 144) using a
      novel method for analyzing Self- verses Relationally oriented qualitative written
      responses to the Suicide Status Form (SSF). A content analysis software program
      was used to extract word counts and a repeated measures longitudinal design was
      implemented to assess improvement over time. Patients with primarily Relationally
      focused word counts were more likely to have a quicker suicide risk resolution
      than those with more Self-focused word counts (6-7 sessions versus 17-18
      sessions). Implications of these data are discussed, including the potential for
      enhancing treatment outcomes using this method with individuals entering
      treatment.

PMID- 26219610
TI  - Toward the improvement in fetal monitoring during labor with the inclusion of
      maternal heart rate analysis.
AB  - Fetal heart rate (FHR) monitoring is used routinely in labor, but conventional
      methods have a limited capacity to detect fetal hypoxia/acidosis. An exploratory
      study was performed on the simultaneous assessment of maternal heart rate (MHR)
      and FHR variability, to evaluate their evolution during labor and their capacity
      to detect newborn acidemia. MHR and FHR were simultaneously recorded in 51
      singleton term pregnancies during the last two hours of labor and compared with
      newborn umbilical artery blood (UAB) pH. Linear/nonlinear indices were computed
      separately for MHR and FHR. Interaction between MHR and FHR was quantified
      through the same indices on FHR-MHR and through their correlation and cross
      entropy. Univariate and bivariate statistical analysis included nonparametric
      confidence intervals and statistical tests, receiver operating characteristic
      curves and linear discriminant analysis. Progression of labor was associated with
      a significant increase in most MHR and FHR linear indices, whereas entropy
      indices decreased. FHR alone and in combination with MHR as FHR-MHR evidenced the
      highest auROC values for prediction of fetal acidemia, with 0.76 and 0.88 for the
      UAB pH thresholds 7.20 and 7.15, respectively. The inclusion of MHR on bivariate
      analysis achieved sensitivity and specificity values of nearly 100 and 89.1%,
      respectively. These results suggest that simultaneous analysis of MHR and FHR may
      improve the identification of fetal acidemia compared with FHR alone, namely
      during the last hour of labor.

PMID- 26219611
TI  - Ocean warming and acidification modulate energy budget and gill ion regulatory
      mechanisms in Atlantic cod (Gadus morhua).
AB  - Ocean warming and acidification are threatening marine ecosystems. In marine
      animals, acidification is thought to enhance ion regulatory costs and thereby
      baseline energy demand, while elevated temperature also increases baseline
      metabolic rate. Here we investigated standard metabolic rates (SMR) and plasma
      parameters of Atlantic cod (Gadus morhua) after 3-4 weeks of exposure to ambient
      and future PCO2 levels (550, 1200 and 2200 uatm) and at two temperatures (10, 18 
      degrees C). In vivo branchial ion regulatory costs were studied in isolated,
      perfused gill preparations. Animals reared at 18  degrees C responded to
      increasing CO2 by elevating SMR, in contrast to specimens at 10  degrees C.
      Isolated gills at 10  degrees C and elevated PCO2 (>=1200 uatm) displayed
      increased soft tissue mass, in parallel to increased gill oxygen demand,
      indicating an increased fraction of gill in whole animal energy budget. Altered
      gill size was not found at 18  degrees C, where a shift in the use of ion
      regulation mechanisms occurred towards enhanced Na(+)/H(+)-exchange and HCO3 (-)
      transport at high PCO2 (2200 uatm), paralleled by higher Na(+)/K(+)-ATPase
      activities. This shift did not affect total gill energy consumption leaving whole
      animal energy budget unaffected. Higher Na(+)/K(+)-ATPase activities in the
      warmth might have compensated for enhanced branchial permeability and led to
      reduced plasma Na(+) and/or Cl(-) concentrations and slightly lowered
      osmolalities seen at 18  degrees C and 550 or 2200 uatm PCO2 in vivo. Overall,
      the gill as a key ion regulation organ seems to be highly effective in supporting
      the resilience of cod to effects of ocean warming and acidification.

PMID- 26219612
TI  - Vitamin D during pregnancy: why observational studies suggest deficiency and
      interventional studies show no improvement in clinical outcomes? A narrative
      review.
AB  - A considerable number of studies have examined vitamin D status during pregnancy.
      Although data from observational studies denote vitamin D hypovitaminosis
      (deficiency or insufficiency) during pregnancy is associated with a plethora of
      adverse maternal and neonatal outcomes, data from interventional
      (supplementation) trials fail to reveal a significant impact on maternal and
      offspring health. The aim of this narrative review was to critically appraise the
      methodology of the most representative published randomized controlled trials in
      an attempt to explain the difference between observational and supplementation
      results. We found that this difference could be attributed to a variety of
      factors, namely: (i) study design (lack of a specific outcome in conjunction with
      timing of supplementation, enrolment of participants with heterogeneous vitamin D
      status); (ii) pitfalls in the interpretation of vitamin D equilibrium (lack of
      determination of plasma half-life); (iii) supplementation regimen (administration
      of a wide range of regimens, in terms of dose, bolus and form); (iv) geographical
      characteristics (vitamin D needs could vary significantly within a country,
      particularly in areas with a wide range of latitude gradient); (v) adaptations of
      vitamin D metabolism during pregnancy (vitamin D and calcium equilibrium are
      changed during pregnancy compared with the non-pregnant state) and (vi)
      supplementation of populations with low baseline 25(OH)D values would likely
      manifest beneficial effects. All these parameters should be taken into
      consideration in the design of future vitamin D supplementation trials. 

PMID- 26219613
TI  - The effect of sphingosine-1-phosphate on bone metabolism in humans depends on its
      plasma/bone marrow gradient.
AB  - BACKGROUND: Although recent studies provide clinical evidence that sphingosine-1
      phosphate (S1P) may primarily affect bone resorption in humans, rather than bone
      formation or the osteoclast-osteoblast coupling phenomenon, those studies could
      not determine which bone resorption mechanism is more important, i.e.,
      chemorepulsion of osteoclast precursors via the blood to bone marrow S1P gradient
      or receptor activator of NF-kappaB ligand (RANKL) elevation in osteoblasts via
      local S1P. AIM: To investigate how S1P mainly contributes to increased bone
      resorption in humans, we performed this case-control study at a clinical unit in
      Korea. METHODS: Blood and bone marrow samples were contemporaneously collected
      from 70 patients who underwent hip surgery due to either osteoporotic hip
      fracture (HF) (n = 10) or other causes such as osteoarthritis (n = 60). RESULTS:
      After adjusting for sex, age, BMI, smoking, alcohol, previous fracture, diabetes,
      and stroke, subjects with osteoporotic HF demonstrated a 3.2-fold higher
      plasma/bone marrow S1P ratio than those without HF, whereas plasma and bone
      marrow S1P levels were not significantly different between these groups.
      Consistently, the risk of osteoporotic HF increased 1.38-fold per increment in
      the plasma/bone marrow S1P ratio in a multivariate adjustment model. However, the
      odds ratios for prevalent HF according to the increment in the plasma and bone
      marrow S1P level were not statistically significant. CONCLUSION: Our current
      results using simultaneously collected blood and bone marrow samples suggest that
      the detrimental effects of S1P on bone metabolism in humans may depend on the S1P
      gradient between the peripheral blood and bone marrow cavity.

PMID- 26219614
TI  - The relationship between the Bispectral Index (BIS) and the Observer Alertness of
      Sedation Scale (OASS) scores during propofol sedation with and without ketamine:
      a randomized, double blinded, placebo controlled clinical trial.
AB  - Prior studies have examined the static effect of intravenous ketamine on the BIS
      Index for sedation but it remains unknown if the BIS Index is a reliable method
      to track sedation levels in the presence of ketamine. The major objective of the
      current investigation was to compare the BIS Vista Index ability to track varying
      depths of sedation as determined by OASS scores in a standardized anesthetic
      regimen with and without ketamine. The study was a randomized, double blinded
      clinical trial. Patients undergoing breast surgery under sedation with propofol
      were randomized to receive ketamine (1.5 MUg kg min(-1)) or saline. Infusion data
      was used to estimate propofol plasma concentrations (Cp). The main outcome of
      interest was the correlation between the BIS Vista Index with the OASS score.
      Twenty subjects were recruited and fifteen completed the study. Four hundred
      fifty-five paired data points were included in the analysis. Model performance
      (Nagelkerke R(2)) of the multinomial logistic regression model was 0.57 with the
      c-statistic of 0.87 (95 % CI 0.82-0.91). Compared to awake the odds ratio for BIS
      values predicting moderate sedation in the saline/propofol group 1.19 (95 % CI
      1.12-1.25) but only 1.06 (95 % CI 1.02-1.1) in the ketamine/propofol group (P =
      0.001). There was no difference in the odds for BIS values to predict deep
      sedation between groups (P = 0.14). The BIS monitor can be used to monitor
      sedation level even when ketamine is used with propofol as part of the sedation
      regimen. However, ketamine reduces the value of the BIS in predicting moderate
      sedation levels. 

PMID- 26219615
TI  - New Antiangiogenetic Therapy Beyond Bevacizumab in the Treatment of Advanced Non
      Small Cell Lung Cancer.
AB  - Lung cancer is the leading cause of death from cancer worldwide with limited
      available treatment options in absence of specific molecular alteration. New
      therapeutic approaches for addressing non small cell lung cancer (NSCLC) are
      urgently needed. Angiogenesis plays a central role in the tumor growth and
      metastatic dissemination which stimulates multiple cells to build new abnormal
      microvessels and leads to tumor microenvironment alterations. This process
      involves many factors, such as, the vascular endothelial growth factor (VEGF)
      that has a dominant role, the fibroblast growth factors (FGFs) and the plateled
      derived growth factor (PDGF) that together contribute to resistance to VEGF/VEGFR
      directed therapy. To date, bevacizumab is currently the only angiogenesis
      inhibitor that has been approved for the treatment of patients with advanced
      NSCLC in first-line setting. Moreover, in the last year, two new antiangiogenic
      agents have been approved for the treatment of patients with advanced NSCLC in
      second line setting. This review describes the new antiangiogenic agents in the
      treatment of advanced NSCLC. 

PMID- 26219617
TI  - [Dyspnea. The most common chief complaints and their differential diagnosis].

PMID- 26219616
TI  - Making Visible a Theory-Guided Advance Care Planning Intervention.
AB  - PURPOSE: In reports of end-of-life communication interventions, it is difficult
      to find sufficient detail about the intervention to allow replication, extension,
      and translation into practice. The purpose of this article is to provide details
      about a theory-guided advance care planning intervention, sharing the patient's
      illness representations to increase trust (SPIRIT), an intervention that has been
      shown to be efficacious for patients and their surrogates with respect to
      preparation for end-of-life decision making. METHODS AND DESIGN: The description
      of SPIRIT is based on an intervention description checklist by Conn (2012), the
      Intervention Taxonomy from Schulz, Czaja, McKay, Ory, and Belle (2010) and on
      relevant segments of Consolidated Standards of Reporting Trials. DISCUSSION: The
      SPIRIT intervention was developed based on sound theoretical underpinnings and
      pilot tested with target patient populations and racial or ethnic groups. We
      describe details about the intervention's theoretical basis, requisite intervener
      training, implementation of each intervention component, and fidelity monitoring.
      CLINICAL RELEVANCE: The details about the components of a theory-guided advance
      care planning intervention may facilitate translation of the intervention to
      practice settings.

PMID- 26219618
TI  - [Dyspnea. Profile of the most important diagnostic tests].
AB  - The diagnostic pathway for the evaluation of patients with dyspnea requires a
      thorough history taking and physical examination. Based on the results of these
      basic steps a broad variety of additional diagnostic tests are available. Each
      test can contribute valuable information when correctly indicated and performed.
      Among these are electrocardiography (ECG), laboratory parameters, X-ray
      examination, echocardiography, spirometry and whole body plethysmography and
      finally spiroergometry. This article presents a focused review of what each of
      these diagnostic modalities can contribute to the diagnostic process for dyspnea.

PMID- 26219619
TI  - [Non-cardiac and non-pulmonary causes of dyspnea].
AB  - In addition to cardiac and pulmonary diseases there is a broad variety of
      different underlying causes of dyspnea. The spectrum includes the different forms
      of anemia, all causes of upper airway obstructions, neuromuscular diseases and
      psychopathological disorders. This article gives a brief review of the entire
      spectrum by providing information about differential diagnostics as well as the
      main therapeutic principles. A field of growing interest is dyspnea in the
      context of palliative care. 

PMID- 26219620
TI  - Chronic Arrhythmias in the Setting of Heterotaxy: Differences between Right and
      Left Isomerism.
AB  - So-called heterotaxy affects lateralization of the thoracic and abdominal organs.
      Congenital malformations may be present in one of several organ systems. Cardiac
      involvement includes both structural and conduction abnormalities. Data regarding
      arrhythmias in heterotaxy come from case reports and small case series. We pooled
      available data to further characterize arrhythmias in heterotaxy. A systematic
      review of the literature for manuscripts describing arrhythmias in heterotaxy
      patients was conducted. Databases including PubMed, EMBASE, and Ovid were
      searched. Studies describing arrhythmias in patients with heterotaxy were
      included if they were in English and presented characteristics of the
      arrhythmias. Arrhythmia characteristics were abstracted and are presented as
      pooled data. Freedom from arrhythmia by age was then analyzed using Kaplan-Meier
      analysis. A total of 19 studies with 121 patients were included in the pooled
      analysis. Those with right isomerism were found to be more likely to have atrial
      flutter, atrial tachycardia, junctional tachycardia, and ventricular tachycardia.
      Those with left isomerism were more likely to have atrioventricular block,
      intraventricular conduction delay, sick sinus syndrome, and atrioventricular
      nodal reentry tachycardia. Median age of onset for all arrhythmias was 4 years
      with no difference by specific arrhythmia or isomerism. Those with right and left
      isomerism are at risk for different arrhythmias but are likely to develop
      arrhythmias at the same age. Those with left isomerism are more likely to require
      pacemaker placement due to atrioventricular block. Understanding these
      differences allows for focused surveillance of development of these arrhythmias.

PMID- 26219621
TI  - Rural health activism over two decades: the Wonca Working Party on Rural Practice
      1992-2012.
AB  - The Wonca Working Party on Rural Practice (WWPRP) was formed in 1992 in response
      to the realization that rural healthcare faced many serious and similar
      challenges around the world. Over the years the members of the committee have
      come from many different countries but found inspiration and strength in
      developing and sharing educational and health system innovations that could be
      modified and applied to different rural settings. The 11 world rural health
      conferences organized by the WWPRP over the first two decades since it was
      founded brought together a range of people, from rural doctors and other front
      line healthcare workers to administrators and educational leaders, who connected
      with and learned from each other to advance rural health care around the world.
      The WWPRP policy documents and conference consensus statements have been
      important in shaping rural health care in a number of different contexts, and
      have led to issues of rural health care rising to prominence on the world stage.
      The WWPRP has throughout been an activist lobby group with a focus on the rural
      communities it serves rather than its members, and enters its third decade with
      much left to be done.

PMID- 26219622
TI  - Dreaming, memory, insomnia and the exploding attention for sleep.

PMID- 26219623
TI  - Corrigendum.

PMID- 26219624
TI  - A case of genetic polyandry in the shortfin mako Isurus oxyrinchus.
AB  - This article documents a case of genetic polyandry in the oceanic and pelagic
      shortfin mako Isurus oxyrinchus and briefly comments on the implications of this
      finding.

PMID- 26219625
TI  - Development of loop-mediated isothermal amplification assays for genotyping of
      Type III Secretion System in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a well-known environmental bacterium capable of causing
      a variety of life-threatening human infections, with a Type III Secretion System
      (T3SS) as the most significant virulence determinant. P. aeruginosa strains
      exhibit unique T3SS virulence genotypes defined by the presence of either exoS or
      exoU. In this study, loop-mediated isothermal amplification (LAMP) assays for
      rapid detection of exoS and exoU in P. aeruginosa have been developed and
      evaluated. Set of four primers were designed for LAMP-based amplification of exoS
      and exoU respectively. The LAMP reactions were performed at 63 degrees C for 40
      min, with detection limits of 100 fg purified DNA. In 107 river water isolates,
      exoS and exoU were detected in 10 (9%) and 89 (83%) isolates, respectively, and
      in 38 soil isolates, they were detected in 7 (18%) and 31 (82%) cases
      respectively. In conclusion, the LAMP assays are rapid, simple and cost-effective
      tools for detection of the exoU- and exoS-types of P. aeruginosa strains.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This method can be used for the rapid,
      sensitive and low-cost detection of genes (exoS and exoU) encoding proteins that
      are part of Type III Secretion System of Pseudomonas aeruginosa. It can serve as
      an efficient method in outbreak situations or in routine surveillance studies to
      judge virulence potential and to investigate pathogenesis of P. aeruginosa.

PMID- 26219627
TI  - Producing a dual-fluorescent molecule by tuning the energetics of excited-state
      intramolecular proton transfer.
AB  - We report herein the selective preparation of normal, tautomeric, and dual
      fluorescent molecules with a common ESIPT core. 2'-Hydroxyacetophenone (OHAP) is
      known as a typical molecule that undergoes excited-state intramolecular hydrogen
      transfer (ESIPT) to display fluorescence emission from the excited state of the
      tautomer. In this study, a series of ten OHAP-cored fluorescent molecules were
      prepared and their excited state properties have been explored. The bathochromic
      shift of the pi-pi* absorption band with pi-extensions of substituents of these
      molecules indicates that the excitation energy of the normal form of the OHAP
      unit was reduced due to the substituents, while the energy of the excited
      tautomer appeared to be independent of the pi-extension of the substituents. When
      pyrene or anthracene was connected at the end (molecules 4 and 5), only normal
      fluorescence appeared, and the tautomer fluorescence disappeared. An anthracene
      derivative (molecule 10) displayed dual fluorescence, indicating that the normal
      and the tautomer excited states were energetically "balanced". A fluorescence
      lifetime analysis revealed the ESIPT reaction rate of 10 to be much slower than
      those of other derivatives and that the normal and tautomer forms were in
      equilibrium in the excited state. 

PMID- 26219626
TI  - Changes in neuronal CycD/Cdk4 activity affect aging, neurodegeneration, and
      oxidative stress.
AB  - Mitochondrial dysfunction has been implicated in human diseases, including
      cancer, and proposed to accelerate aging. The Drosophila Cyclin-dependent protein
      kinase complex cyclin D/cyclin-dependent kinase 4 (CycD/Cdk4) promotes cellular
      growth by stimulating mitochondrial biogenesis. Here, we examine the
      neurodegenerative and aging consequences of altering CycD/Cdk4 function in
      Drosophila. We show that pan-neuronal loss or gain of CycD/Cdk4 increases
      mitochondrial superoxide, oxidative stress markers, and neurodegeneration and
      decreases lifespan. We find that RNAi-mediated depletion of the mitochondrial
      transcription factor, Tfam, can abrogate CycD/Cdk4's detrimental effects on both
      lifespan and neurodegeneration. This indicates that CycD/Cdk4's pathological
      consequences are mediated through altered mitochondrial function and a
      concomitant increase in reactive oxygen species. In support of this, we
      demonstrate that CycD/Cdk4 activity levels in the brain affect the expression of
      a set of 'oxidative stress' genes. Our results indicate that the precise
      regulation of neuronal CycD/Cdk4 activity is important to limit mitochondrial
      reactive oxygen species production and prevent neurodegeneration. 

PMID- 26219628
TI  - Dynamic phase diagram of soft nanocolloids.
AB  - We present a comprehensive experimental and theoretical study covering micro-,
      meso- and macroscopic length and time scales, which enables us to establish a
      generalized view in terms of structure-property relationship and equilibrium
      dynamics of soft colloids. We introduce a new, tunable block copolymer model
      system, which allows us to vary the aggregation number, and consequently its
      softness, by changing the solvophobic-to-solvophilic block ratio (m : n) over two
      orders of magnitude. Based on a simple and general coarse-grained model of the
      colloidal interaction potential, we verify the significance of interaction length
      sigmaint governing both structural and dynamic properties. We put forward a
      quantitative comparison between theory and experiment without adjustable
      parameters, covering a broad range of experimental polymer volume fractions
      (0.001 <=phi<= 0.5) and regimes from ultra-soft star-like to hard sphere-like
      particles, that finally results in the dynamic phase diagram of soft colloids. In
      particular, we find throughout the concentration domain a strong correlation
      between mesoscopic diffusion and macroscopic viscosity, irrespective of softness,
      manifested in data collapse on master curves using the interaction length
      sigmaint as the only relevant parameter. A clear reentrance in the glass
      transition at high aggregation numbers is found, recovering the predicted hard
      sphere (HS) value in the hard-sphere like limit. Finally, the excellent agreement
      between our new experimental systems with different but already established model
      systems shows the relevance of block copolymer micelles as a versatile
      realization of soft colloids and the general validity of a coarse-grained
      approach for the description of the structure and dynamics of soft colloids. 

PMID- 26219629
TI  - Comment: The midline.

PMID- 26219630
TI  - Common neural correlates of emotion perception in humans.
AB  - Whether neuroimaging findings support discriminable neural correlates of emotion
      categories is a longstanding controversy. Two recent meta-analyses arrived at
      opposite conclusions, with one supporting (Vytal and Hamann []: J Cogn Neurosci
      22:2864-2885) and the other opposing this proposition (Lindquist et al. []: Behav
      Brain Sci 35:121-143). To obtain direct evidence regarding this issue, we
      compared activations for four emotions within a single fMRI design. Angry, happy,
      fearful, sad and neutral stimuli were presented as dynamic body expressions. In
      addition, observers categorized motion morphs between neutral and emotional
      stimuli in a behavioral experiment to determine their relative sensitivities.
      Brain-behavior correlations revealed a large brain network that was identical for
      all four tested emotions. This network consisted predominantly of regions located
      within the default mode network and the salience network. Despite showing brain
      behavior correlations for all emotions, muli-voxel pattern analyses indicated
      that several nodes of this emotion general network contained information capable
      of discriminating between individual emotions. However, significant
      discrimination was not limited to the emotional network, but was also observed in
      several regions within the action observation network. Taken together, our
      results favor the position that one common emotional brain network supports the
      visual processing and discrimination of emotional stimuli.

PMID- 26219631
TI  - Effects of Alkyl Chain Length and Hydrogen Bonds on the Cooperative Self-Assembly
      of 2-Thienyl-Type Diarylethenes at a Liquid/Highly Oriented Pyrolytic Graphite
      (HOPG) Interface.
AB  - An appropriate understanding of the process of self-assembly is of critical
      importance to tailor nanostructured order on 2D surfaces with functional
      molecules. Photochromic compounds are promising candidates for building blocks of
      advanced photoresponsive surfaces. To investigate the relationship between
      molecular structure and the mechanism of ordering formation, 2-thienyl-type
      diarylethenes with various lengths of alkyl side chains linked through an amide
      or ester group were synthesized. Their self-assemblies at a liquid/solid
      interface were investigated by scanning tunneling microscopy (STM). The
      concentration dependence of the surface coverage was analyzed by using a
      cooperative model for a 2D surface based on two characteristic parameters: the
      nucleation equilibrium constant (Kn) and the elongation equilibrium constant
      (Ke). The following conclusions can be drawn. 1) The concentration at which a
      stable 2D molecular ordering is observed by STM exponentially decreases with
      increasing length of the alkyl chain. 2) Compounds bearing amide groups have
      higher degrees of cooperativity in self-assembly on 2D surfaces (i.e., sigma,
      which is defined as Kn/Ke) than compounds with ester groups. 3) The self-assembly
      process of the open-ring isomer of an ester derivative is close to isodesmic,
      whereas that of the closed-ring isomer is cooperative because of the difference
      in equilibrium constants for the nucleation step (i.e., Kn) between the two
      isomers.

PMID- 26219632
TI  - Amphiphilic Nanoparticles Control the Growth and Stability of Lipid Bilayers with
      Open Edges.
AB  - Molecular amphiphiles self-assemble in polar media to form ordered structures
      such as micelles and vesicles essential to a broad range of industrial and
      biological processes. Some of these architectures such as bilayer sheets, helical
      ribbons, and hollow tubules are potentially useful but inherently unstable owing
      to the presence of open edges that expose the hydrophobic bilayer core. Here, we
      describe a strategy to stabilize open bilayer structures using amphiphilic
      nanoparticle surfactants that present mixtures of hydrophilic and hydrophobic
      ligands on their surface. We observe that these particles bind selectively to the
      open edge of bilayer membranes to stabilize otherwise transient amphiphile
      assemblies. We show how such particles can precisely control the size of lipid
      tubules, how they can inhibit the formation of undesirable assemblies such as
      gallstone precursors, and how they can stabilize free-floating lipid microdiscs. 

PMID- 26219633
TI  - Differentials in the prevalence of anemia among non-pregnant, ever-married women
      in Bangladesh: multilevel logistic regression analysis of data from the 2011
      Bangladesh Demographic and Health Survey.
AB  - BACKGROUND: Anemia is one of the most common public health problems globally, and
      high prevalence has been reported among women of reproductive age, especially in
      developing countries. This study was conducted to evaluate differentials in the
      prevalence of anemia among non-pregnant, ever-married women of reproductive age
      in Bangladesh, and to examine associations with demographic, socioeconomic, and
      nutritional factors. METHODS: Data for this cross-sectional study were taken from
      the 2011 Bangladesh Demographic and Health Survey (BDHS). In a sub-sample of one
      third of the households, all ever-married women of reproductive age (15 to 49
      years) were selected for the biomarker component of the survey, including anemia.
      The sample size for our study was 5,293. Data were analyzed using multilevel
      logistic regression analysis. RESULTS: The prevalence of anemia among non
      pregnant, ever-married women was 41.3% (urban: 37.2% and rural: 43.5%). Among
      anemic women, 35.5% had mild anemia, 5.6% had moderate anemia, and 0.2% had
      severe anemia. Women with no education were more likely to be anemic than those
      with secondary education (p < 0.01) or higher education (p < 0.01).
      Undernourished women (BMI < 18.5) were at greater risk of anemia (p < 0.01)
      compared with normal women, overweight women, and obese women. Anemia was less
      pronounced among non-pregnant women using contraception (p < 0.05), Muslim women
      (p < 0.01), and women living in rich households (p < 0.01). CONCLUSIONS: The
      prevalence of anemia among non-pregnant, ever-married women in Bangladesh is
      high. Illiteracy, poverty, and undernutrition are contributing factors.

PMID- 26219634
TI  - Bioactivity characterization of Lactobacillus strains isolated from dairy
      products.
AB  - This study aimed to find candidate strains of Lactobacillus isolated from sheep
      dairy products (yogurt and ewe colostrum) with probiotic and anticancer activity.
      A total of 100 samples were randomly collected from yogurt and colostrum and 125
      lactic acid bacteria were isolated. Of these, 17 Lactobacillus strains belonging
      to five species (L. delbrueckii, L. plantarum, L. rhamnosus, L. paracasei, and L.
      casei) were identified. L. plantarum 17C and 13C, which isolated from colostrums,
      demonstrated remarkable results such as resistant to low pH and high
      concentrations of bile salts, susceptible to some antibiotics and good
      antimicrobial activity that candidate them as potential probiotics. Seven strains
      (1C, 5C, 12C, 13C, 17C, 7M, and 40M), the most resistant to simulated digestion,
      were further investigated to evaluate their capability to adhere to human
      intestinal Caco-2 cells. L. plantarum 17C was the most adherent strain. The
      bioactivity assessment of L. plantarum 17C showed anticancer effects via the
      induction of apoptosis on HT-29 human cancer cells and negligible side effects on
      one human epithelial normal cell line (FHs 74). The metabolites produced by this
      strain can be used as alternative pharmaceutical compounds with promising
      therapeutic indices because they are not cytotoxic to normal mammalian cells. 

PMID- 26219635
TI  - On the short circuit resilience of organic solar cells: prediction and
      validation.
AB  - The operational characteristics of organic solar cells manufactured with large
      area processing methods suffers from the occurrence of short-circuits due to
      defects in the photoactive thin film stack. In this work we study the effect of a
      shunt resistance on an organic solar cell and demonstrate that device performance
      is not affected negatively as long as the shunt resistance is higher than
      approximately 1000 Ohm. By studying charge transport across PEDOT: PSS-lithium
      fluoride/aluminum (LiF/Al) shunting junctions we show that this prerequisite is
      already met by applying a sufficiently thick (>1.5 nm) LiF layer. We demonstrate
      that this remarkable shunt-resilience stems from the formation of a significant
      charge transport barrier at the PEDOT: PSS-LiF/Al interface. We validate our
      predictions by fabricating devices with deliberately severed photoactive layers
      and find an excellent agreement between the calculated and experimental current
      voltage characteristics.

PMID- 26219636
TI  - A heat flux modulator from carbon nanotubes.
AB  - For a heat flux modulator, the most difficult problem is that the main carriers
      named 'phonons' have little response to external fields. Of the existing studies
      on heat flux modulators, most were theoretical work and the materials systems for
      the theoretical calculations were artificial lattices. In this paper, we made a
      heat modulator with ultrathin buckypaper which was made of multi-layer carbon
      nanotube sheets overlapped together, and achieved an on/off ratio whose value was
      1.41 using an pendent block in experiments without special optimizations. When
      the temperatures of the two sides were of appropriate values, we could even see a
      negative heat flux. Intuitively, the heat flux was tuned by the gap between the
      buckypaper and the pendent gate, and we observed that there was heat transferred
      to the pendent block. The structure of the modulator is similar to a CNT
      transistor with a contactless gate, hence this type of micromodulator will be
      easy to manufacture in the future. 

PMID- 26219637
TI  - An effective combination of electrodeposition and layer-by-layer assembly to
      construct composite films with luminescence switching behavior.
AB  - This article presents a combination strategy of electrodeposition and a layer-by
      layer assembly to fabricate functional composite films with luminescence
      switching behavior. Firstly, a novel green luminescence film consisting of 8
      hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HOPTS) was first obtained on
      ITO by a facile electrodeposition method. Then, the multilayer films containing
      different layers of tungstophosphate K12.5Na1.5[NaP5W30O110].15H2O (P5W30) were
      further fabricated on the green luminescence film to form the composite films
      [(HOPTS)50/(PDDA/P5W30)n] (n = 10, film 1; n = 27, film 2; n = 57, film 3).
      Cyclic voltammetry and fluorescence spectroscopy were used to characterize the
      electrochemical activity of P5W30 and the luminescence property of HOPTS in the
      composite films, respectively. Lastly, in situ UV-Vis spectroelectrochemical and
      fluorescence spectroelectrochemical measurements were applied to investigate the
      luminescence switching behaviors of the composite films controlled by the
      electrochromism component of P5W30 upon electrochemical modulation. In summary,
      the investigation results revealed that the electrodeposition method is
      convenient and rapid, and thus-prepared composite films showed improved
      luminescence switching performance in terms of switching process, activation
      cycles, coloration efficiency, and bleached-state transparency as well as good
      stability, wide voltage range and good reversibility. Therefore, the present
      study offers a new fabrication route for the multifunctional composite films
      through an effective combination of electrodeposition and layer-by-layer assembly
      technique. 

PMID- 26219638
TI  - Pharmacokinetics of fluticasone propionate multidose, inhalation-driven, novel,
      dry powder inhaler versus Diskus and metered-dose inhalers.
AB  - BACKGROUND: A novel inhalation-driven multidose dry powder inhaler (MDPI) that
      eliminates the need for the patient to coordinate device actuation with
      inhalation has been developed for delivery of inhaled asthma medications.
      OBJECTIVE: To characterize the pharmacokinetics of single-dose fluticasone
      propionate (Fp) MDPI compared with single doses of Fp Diskus (a dry powder
      inhaler) and a metered-dose inhaler (MDI) in healthy subjects. METHODS: This was
      a single-center, open-label, randomized, three-period crossover, single-dose
      pilot study in healthy adults ages 18 to 45 years. Eligible subjects (N = 18)
      were randomized to one of six treatment sequences that contained three treatment
      arms: Fp MDPI 400 micrograms/inhalation X two inhalations (800 micrograms total
      dose); Fp Diskus 250 micrograms/inhalation X four (1000 micrograms total dose);
      and Fp MDI 220 micrograms/inhalation X four (880 micrograms total dose).
      Pharmacokinetics (area under concentration-versus- time curve [AUC], maximum
      plasma concentration [Cmax], time to Cmax [tmax], and elimination half-life
      [t1/2]), safety, and tolerability were assessed for each treatment. RESULTS:
      Plasma Fp concentration-versus-time curves were comparable across treatments.
      Geometric mean AUC 0-t and Cmax for Fp MDPI 800 micrograms were 19% and 18%
      higher, respectively, compared with Fp Diskus 1000 micrograms, and 47% and 82%
      higher, respectively, compared with Fp MDI 880 micrograms. Median tmax (60.0-60.6
      minutes) and median t1/2 (9.1-9.8 hours) were comparable across the three
      treatments. Single-dose Fp was well tolerated, with no new safety issues noted.
      CONCLUSION: Single-dose administration of Fp MDPI 800 micrograms produced
      systemic exposure comparable with those for Fp Diskus 1000 micrograms and Fp MDI
      880 micrograms.

PMID- 26219639
TI  - The influence of phosphorothioate on charge migration in single and double
      stranded DNA: a theoretical approach.
AB  - In this study the influence of the phosphorothioate internucleotide bond on the
      electronic properties of single and double-stranded short nucleotides has been
      investigated at the M06-2X/6-31+G** level of theory in the gaseous phase. Due to
      the chirality of the phosphorus atom in a phosphorothioate (PT) internucleotide
      diester bond, the adiabatic/vertical mode of electron affinity/ionization
      potential, spin density and molecular orbital distribution, as well as structural
      analysis were taken under consideration for the single stranded (ss) R(P) and
      S(P) diastereomers of d[G(PS)G] and for double stranded (ds) d[G(PS)G]*d[C(PO)C],
      in comparison with the corresponding parent phosphate compounds. Moreover, the
      excitation states, HOMO and LUMO energies were calculated using a TD-DFT
      methodology at the M06-2X/6-31+G**//M06-2X/6-31++G** level of theory in the
      aqueous phase. The obtained results show that the PT plays a significant role in
      the case of ss-oligonucleotides, and to a much smaller extent in ds-oligomers.

PMID- 26219640
TI  - The use of low doses of acepromazine as an aid for lameness diagnosis in horses:
      An accelerometric evaluation.
AB  - OBJECTIVES: The aim of the present study was to quantify by accelerometry the
      trotting pattern of adult horses sedated with two different doses of
      acepromazine, in order to assess the use of this drug in equine lameness
      evaluations. METHODS: Seven mature horses were used and three treatments were
      administered to each horse: saline solution, acepromazine (0.01 mg/kg), and
      acepromazine (0.02 mg/kg). The portable gait analyzer used consisted of three
      orthogonal accelerometers that measure accelerations along the dorsoventral,
      longitudinal, and lateral axes. Baseline values were obtained and after
      treatment, accelerometric recordings were repeated every five minutes during the
      first 20 minutes after the injection and then every 10 minutes thereafter for two
      hours. Ground-to-lip distance was also measured. RESULTS: Administration of
      acepromazine decreased some of the variables investigated and differences between
      doses were observed. Speed, stride frequency, and stride length were
      significantly reduced following treatments. For coordination parameters, no
      significant differences among values were observed. Energetic variables suffered
      only weak reductions whereas ground-to-lip distance values were significantly
      decreased up to 120 minutes after treatment. CLINICAL SIGNIFICANCE: Acepromazine
      produces significant alterations in the gait pattern with differences between
      doses, but it does not affect coordination variables in normal unexcited horses,
      and at a dose of 0.01 mg/kg may be the tranquilizer of choice for evaluating
      lameness in this setting.

PMID- 26219643
TI  - smRithm: Graphical user interface for heart rate variability analysis.
AB  - Over the past 25 years, Heart rate variability (HRV) has become a non-invasive
      research and clinical tool for indirectly carrying out investigation of both
      cardiac and autonomic system function in both healthy and diseased. It provides
      valuable information about a wide range of cardiovascular disorders, pulmonary
      diseases, neurological diseases, etc. Its primary purpose is to access the
      functioning of the nervous system. The source of information for HRV analysis is
      the continuous beat to beat measurement of inter-beat intervals. The
      electrocardiography (ECG or EKG) is considered as the best way to measure inter
      beat intervals. This paper proposes an open source Graphical User Interface
      (GUI): smRithm developed in MATLAB for HRV analysis that will apply effective
      techniques on the raw ECG signals to process and decompose it in a simpler manner
      to obtain more useful information out of signals that can be utilized for more
      powerful and efficient applications in the near future related to HRV. 

PMID- 26219642
TI  - "And then you start to loose it because you think about Nutella": The
      significance of food for people with inflammatory bowel disease - a qualitative
      study.
AB  - BACKGROUND: Many patients with inflammatory bowel disease strongly believe that
      food or certain food products heavily influence the symptoms or even trigger
      acute flare-ups. Unfortunately, there is no generalizable information for these
      patients, and therefore no effective diet has been identified to date. METHODS:
      The narrative interviews we used for this study provide the basis for the German
      website www.krankheitserfahrungen.de . Maximum-variation sampling was used to
      include a broad range of experiences and a variety of different factors that
      might influence people's experiences. The sample included men and women of
      different age groups and social and ethnic backgrounds from across Germany. The
      interviews were analyzed using grounded theory. RESULTS: Four interrelated
      categories emerged: managing uncertainty, eating: between craving and aversion,
      being different and professional help as a further source of uncertainty. The
      most important issue for our responders was the handling of uncertainty and to
      find a way between desire for, and aversion against, eating. Many participants
      described difficulties during formal social occasions such as weddings,
      birthdays, or when going out to a restaurant. CONCLUSIONS: Many of the
      experiences the participants reported in their daily struggle with food and their
      illness, such as cravings for and abstaining from certain foods, were rather
      unusual and often stressful. Because they decided not to go out in public any
      longer, some of the interviewees experienced even more social isolation than they
      did before. Health professionals need to become more involved and not only advice
      about food and eating, but also help their patients find strategies for avoiding
      social isolation.

PMID- 26219647
TI  - Clinical Implications of Changes in Individual Platelet Reactivity to Aspirin
      Over Time in Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Time-dependent changes in individual platelet reactivity
      have been detected in patients with coronary artery disease. Therefore, we sought
      to evaluate the time-dependent changes in platelet reactivity to aspirin during
      the acute stage after ischemic stroke and the clinical implications of variable
      patient responses to aspirin in acute ischemic stroke. METHODS: We conducted a
      single-center, prospective, observational study. The acute aspirin reaction unit
      (ARU) was measured after 3 hours of aspirin loading, with higher values
      indicating increased platelet reactivity despite aspirin therapy. The follow-up
      ARU was measured on the fifth day of consecutive aspirin intake. The numeric
      difference between the follow-up ARU and the acute ARU was defined as DeltaARU
      and was stratified into quartiles. Early neurological deterioration was regarded
      as an early clinical outcome. RESULTS: Both the acute ARU (476+/-69 IU) and the
      follow-up ARU (451+/-68 IU) were measured in 349 patients in this study. Early
      neurological deterioration was observed in 72 patients (20.6%). Changes in
      aspirin platelet reactivity over time showed an approximately Gaussian
      distribution. The highest DeltaARU quartile was independently associated with
      early neurological deterioration (odds ratio, 3.19; 95% confidence interval, 1.43
      7.10; P=0.005) by multivariate logistic regression analysis. CONCLUSIONS: The
      results of our study showed that the increase in platelet reactivity to aspirin
      over time is independently associated with early neurological deterioration in
      patients with acute ischemic stroke. In addition, during the acute stage of
      ischemic stroke, serial platelet reactivity assays may be more useful than a
      single assay for identifying the clinical implications of aspirin platelet
      reactivity after ischemic stroke.

PMID- 26219641
TI  - Alphavirus RNA synthesis and non-structural protein functions.
AB  - The members of the genus Alphavirus are positive-sense RNA viruses, which are
      predominantly transmitted to vertebrates by a mosquito vector. Alphavirus disease
      in humans can be severely debilitating, and depending on the particular viral
      species, infection may result in encephalitis and possibly death. In recent
      years, alphaviruses have received significant attention from public health
      authorities as a consequence of the dramatic emergence of chikungunya virus in
      the Indian Ocean islands and the Caribbean. Currently, no safe, approved or
      effective vaccine or antiviral intervention exists for human alphavirus
      infection. The molecular biology of alphavirus RNA synthesis has been well
      studied in a few species of the genus and represents a general target for
      antiviral drug development. This review describes what is currently understood
      about the regulation of alphavirus RNA synthesis, the roles of the viral non
      structural proteins in this process and the functions of cis-acting RNA elements
      in replication, and points to open questions within the field. 

PMID- 26219646
TI  - Intravenous Bone Marrow Stem Cell Grafts Preferentially Migrate to Spleen and
      Abrogate Chronic Inflammation in Stroke.
AB  - BACKGROUND AND PURPOSE: Adult stem cell therapy is an experimental stroke
      treatment. Here, we assessed homing and anti-inflammatory effects of bone marrow
      stromal cells (hBMSCs) in chronic stroke. METHODS: At 60 days post stroke, adult
      Sprague-Dawley rats received intravenous hBMSCs (4*10(6) labeled or nonlabeled
      cells) or vehicle (saline). A sham surgery group served as additional control. In
      vivo imaging was conducted between 1 hour and 11 days post transplantation,
      followed by histological examination. RESULTS: Labeled hBMSCs migrated to spleen
      which emitted significantly higher fluorescent signal across all time points,
      especially during the first hour, and were modestly detected in the head region
      at the 12 hours and 11 days, compared with nonlabeled hBMSCs and vehicle-infused
      stroke animals, or sham (P<0.05). At 11 days post transplantation, ex vivo
      imaging confirmed preferential hBMSC migration to the spleen over the brain.
      Hematoxylin and eosin staining revealed significant 15% and 30% reductions in
      striatal infarct and peri-infarct area, and a trend of rescue against neuronal
      loss in the hippocampus. Unbiased stereology showed significant 75% and 60%
      decrements in major histocompatibility complex II-activated inflammatory cells in
      gray and white matter, and a 43% diminution in tumor necrosis factor-alpha cell
      density in the spleen of transplanted stroke animals compared with vehicle
      infused stroke animals (P<0.05). Human antigen immunostaining revealed 0.03%
      hBMSCs survived in spleen and only 0.0007% in brain. MSC migration to spleen, but
      not brain, inversely correlated with reduced infarct, peri-infarct, and
      inflammation. CONCLUSIONS: hBMSC transplantation is therapeutic in chronic stroke
      possibly by abrogating the inflammation-plagued secondary cell death.

PMID- 26219648
TI  - Vascular Neurologists as Directors of Stroke Centers in the United States.
AB  - BACKGROUND AND PURPOSE: Hospital certification as primary and comprehensive
      stroke center is associated with improvement in care. We aimed to characterize
      the leadership at stroke centers nationwide to determine the proportion led by
      vascular neurologists, a board-recognized subspecialty focusing on stroke care.
      METHODS: We identified hospitals in the United States holding primary and
      comprehensive stroke center designation as of September 2013. We contacted each
      hospital to identify the medical director and used data from relevant medical
      boards to determine specialization. Sex and date of medical school graduation
      were obtained from an online physician database. RESULTS: Of the 1167 primary and
      50 comprehensive stroke center hospitals certified by the Joint Commission
      (n=1114), Det Norske Veritas (n=68), and Healthcare Facilities Accreditation
      Program (n=35), we identified the director in 940 (77%). Leadership was most
      often by a neurologist (n=745; 79%) followed by physicians in emergency medicine
      (n=58; 6%) and internal medicine (n=17; 2%). Vascular neurologists (n=319) led
      about one-third of stroke centers. Directors were mostly men (n=764; 81%), with a
      median number of years after medical school graduation of 25 (interquartile
      range, 18-34). Comprehensive stroke centers were more likely than primary stroke
      centers to have leadership by vascular neurologist (77%, n=37 versus 32%, n=282;
      P<0.001). CONCLUSIONS: Vascular neurologist led about one-third of stroke
      centers. There is opportunity for vascular neurologists to increase their role in
      stroke center directorship.

PMID- 26219650
TI  - Combined Multimodal Computed Tomography Score Correlates With Futile
      Recanalization After Thrombectomy in Patients With Acute Stroke.
AB  - BACKGROUND AND PURPOSE: Futile recanalization after acute ischemic stroke occurs
      in almost half of the patients despite optimal angiographic results. Multimodal
      neuroimaging may help to improve patient's selection but is still dismissed by
      many interventionalists. Our aim was to evaluate the accuracy of each parameter
      of multimodal computed tomography (CT) and their combination for predicting
      futile recanalization after successful thrombectomy. METHODS: We retrospectively
      reviewed a cohort of consecutive patients with anterior circulation stroke, fully
      assessable multimodal CT, and successful recanalization. Nonenhanced CT, CT
      angiography source images, cerebral blood volume (CBV), cerebral blood flow
      (CBF), and mismatch CBV-CBF maps were studied by Alberta Stroke Program Early CT
      Score (ASPECTS); collaterals on CT angiography were graded as poor or good (<=50%
      or >50% of the middle cerebral artery territory). Futile recanalization was
      defined as modified Rankin Scale score >2 at 3 months despite successful
      recanalization. RESULTS: One hundred fifty patients were included and 57% of them
      had futile recanalization. They had lower ASPECTS on nonenhanced CT, CT
      angiography source images, CBV, CBF, and mismatch CBV-CBF and presented more
      frequently poor collaterals (all P<0.001). Among them, CBV showed the highest
      area under the curve (0.83; 95% confidence interval, 0.76-0.88). In multivariate
      analyses, CT angiography source images <=5 (odds ratio, 5.1; 95% confidence
      interval, 1.2-21.9), CBV<=6 (odds ratio, 3.5; 95% confidence interval, 1.2-9.7),
      and poor collaterals (odds ratio, 8.6; 95% confidence interval, 1.8-41.7) were
      independent predictors of futile recanalization. A combined score of these 3
      parameters added complementary information: 57% of the patients with score-1, 89%
      with score-2, and 100% with score-3 had futile recanalization. Reclassification
      analyses indicated that this score improved prediction of futile recanalization.
      CONCLUSIONS: In this population, a combined multimodal CT score predicted futile
      recanalization.

PMID- 26219649
TI  - Associations of Circulating Growth Differentiation Factor-15 and ST2
      Concentrations With Subclinical Vascular Brain Injury and Incident Stroke.
AB  - BACKGROUND AND PURPOSE: Growth differentiation factor-15 (GDF-15) and soluble
      (s)ST2 are markers of cardiac and vascular stress. We investigated the
      associations between circulating concentrations of these biomarkers and incident
      stroke and subclinical vascular brain injury in a sample from the Framingham
      Offspring cohort. METHODS: We followed 3374 stroke- and dementia-free individuals
      (mean age, 59.0+/-9.7 years; 53% women) attending the Framingham Offspring sixth
      examination cycle 11.8+/-3.0 years for incident stroke. A subsample of 2463
      individuals underwent brain magnetic resonance imaging and neuropsychological
      testing ~4.0+/-1.7 years after the sixth examination. RESULTS: After adjustment
      for traditional cardiovascular risk factors, B-type natriuretic peptide, high
      sensitivity C-reactive protein, and urine albumin levels, higher stress biomarker
      levels were associated cross-sectionally with lower brain volumes (beta
      coefficients for intracranial volume comparing fourth [Q4] versus first biomarker
      [Q1] quartiles: -0.71% for GDF-15; P=0.002 and 0.47% for sST2; P=0.02) and worse
      performance on the visual reproduction test (beta coefficients for Q4 versus Q1: 
      0.62 for GDF-15; P=0.009 and -0.40 for sST2; P=0.04). Higher GDF-15
      concentrations were also associated with greater log-transformed white-matter
      hyperintensity volumes (beta for Q4 versus Q1=0.19; P=0.01). Prospectively, a
      total of 203 (6%) individuals developed incident stroke/transient ischemic attack
      during follow-up. After multivariable adjustment, sST2 remained significantly
      associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1
      of 1.76, 95% confidence interval of 1.06 to 2.92, and P=0.03. CONCLUSIONS:
      Circulating GDF-15 and sST2 are associated with subclinical brain injury and
      cognitive impairment. Higher sST2 concentrations are also associated with
      incident stroke, suggesting potential links between cardiac stress biomarkers and
      brain injury.

PMID- 26219651
TI  - Role of Neurexin-1beta and Neuroligin-1 in Cognitive Dysfunction After
      Subarachnoid Hemorrhage in Rats.
AB  - BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in
      the formation, maintenance, and regulation of synaptic structures. This study is
      to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid
      hemorrhage (SAH)-induced cognitive dysfunction. METHODS: In vivo, 228 Sprague
      Dawley rats were used. An experimental SAH model was induced by single blood
      injection to prechiasmatic cistern. Primary cultured hippocampal neurons were
      exposed to oxyhemoglobin to mimic SAH in vitro. Specific small interfering RNAs
      and expression plasmids for neurexin-1beta and neuroligin-1 were exploited both
      in vivo and in vitro. Western blot, immunofluorescence, immunoprecipitation,
      neurological scoring, and Morris water maze were performed to evaluate the
      mechanism of neurexin-1beta and neuroligin-1, as well as neurological outcome.
      RESULTS: Both in vivo and in vitro experiments showed SAH-induced decrease in the
      expressions of neurexin-1beta and neuroligin-1 and the interaction between
      neurexin-1beta and neuroligin-1 in neurons. In addition, the interaction between
      neurexin-1beta and neuroligin-1 was reduced by their knockdown and increased by
      their overexpression. The formation of excitatory synapses was inhibited by
      oxyhemoglobin treatment, which was significantly ameliorated by overexpression of
      neurexin-1beta and neuroligin-1 and aggravated by the knockdown of neurexin-1beta
      and neuroligin-1. More importantly, neurexin-1beta and neuroligin-1
      overexpression ameliorated SAH-induced cognitive dysfunction, whereas neurexin
      1beta and neuroligin-1 knockdown induced an opposite effect. CONCLUSIONS:
      Enhancing the expressions of neurexin-1beta and neuroligin-1 could promote the
      interaction between them and the formation of excitatory synapses, which is
      helpful to improve cognitive dysfunction after SAH. Neurexin-1beta and neuroligin
      1 might be good targets for improving cognitive function after SAH.

PMID- 26219652
TI  - Temperature Management and Nursing Care of the Patient With Acute Ischemic
      Stroke.

PMID- 26219653
TI  - Blood pressure variability is associated with increased risk of heart disease and
      death, study finds.

PMID- 26219654
TI  - Size effects and strain localization in atomic-scale cleavage modeling.
AB  - In this work, we study the adhesion and decohesion of Cu(1 0 0) surfaces using
      density functional theory (DFT) calculations. An upper stress to surface
      decohesion is obtained via the universal binding energy relation (UBER), but the
      model is limited to rigid separation of bulk-terminated surfaces. When structural
      relaxations are included, an unphysical size effect arises if decohesion is
      considered to occur as soon as the strain energy equals the energy of the newly
      formed surfaces. We employ the nudged elastic band (NEB) method to show that this
      size effect is opposed by a size-dependency of the energy barriers involved in
      the transition. Further, we find that the transition occurs via a localization of
      bond strain in the vicinity of the cleavage plane, which resembles the strain
      localization at the tip of a sharp crack that is predicted by linear elastic
      fracture mechanics. 

PMID- 26219655
TI  - Bone morphogenetic protein 2 promotes primordial follicle formation in the ovary.
AB  - Primordial follicles (PF) are formed when somatic cells differentiate into
      flattened pregranulosa cells, invaginate into the oocyte nests and encircle
      individual oocytes. We hypothesize that BMP2 regulates PF formation by promoting
      the transition of germ cells into oocytes and somatic cells into pregranulosa
      cells. E15 hamster ovaries were cultured for 8 days corresponding to postnatal
      day 8 (P8) in vivo, with or without BMP2, and the formation of PF was examined.
      BMP2 was expressed in the oocytes as well as ovarian somatic cells during
      development. BMP2 exposure for the first two days or the last two days or the
      entire 8 days of culture led to increase in PF formation suggesting that BMP2
      affected both germ cell transition and somatic cell differentiation. Whereas an
      ALK2/3 inhibitor completely blocked BMP2-induced PF formation, an ALK2-specific
      inhibitor was partially effective, suggesting that BMP2 affected PF formation via
      both ALK2 and ALK3. BMP2 also reduced apoptosis in vitro. Further, more meiotic
      oocytes were present in BMP2 exposed ovaries. In summary, the results provide the
      first evidence that BMP2 regulates primordial follicle formation by promoting
      germ cell to oocyte transition and somatic cell to pre-granulosa cells formation
      and it acts via both ALK2 and ALK3. 

PMID- 26219656
TI  - Saliva amylase as a measure of sympathetic change elicited by autogenic training
      in patients with functional somatic syndromes.
AB  - The aim of this study was to discuss the effect of autogenic training (AT) on
      patients with functional somatic syndrome (FSS) using salivary amylase, the skin
      temperature of the finger, subjective severity of symptoms, and psychological
      characteristics as measures. We assessed 20 patients with FSS and 23 healthy
      controls before and after AT. Baseline levels of salivary amylase prior to an AT
      session were significantly higher in the FSS group than in the control group.
      However, this difference was not significant after AT. The skin temperature of
      the finger increased after AT in both the FSS and control groups. AT contributed
      to the improvement of somatic symptoms in patients with FSS. Our results
      regarding psychological characteristics suggest that mood disturbances are deeply
      involved in the pathology of FSS. Individuals with FSS exhibited elevated levels
      of sympathetic activity compared with healthy controls. Our data indicates that
      AT eased dysregulation of the autonomic nervous system in patients with FSS.
      Thus, salivary amylase may be a useful index of change induced by AT in patients
      with FSS. 

PMID- 26219657
TI  - The relationship between coma near coma, disability ratings, and event-related
      potentials in patients with disorders of consciousness: a semantic association
      task.
AB  - The present research explored the relationship between different measures of
      disorders of consciousness (DOC), that is electrophysiological measures (ERP
      N400, event-related potentials) and clinical measures (Coma Near Coma, CNC;
      Disability Rating Scale, DRS). This analysis aimed to verify the preservation of
      semantic linguistic processes in eighteen patients with DOC. Patients in
      minimally conscious state (MCS) and in vegetative state (VS) were compared with
      respect of N400 amplitude and latency measures. They were submitted to an
      associative auditory task that included congruous (related final words) or
      incongruous (unrelated final words) word sequences. Firstly, an increased N400
      peak amplitude within the fronto-central cortical areas was revealed in response
      to incongruous sequences for all patients. Moreover, this peak was temporally
      delayed in response to incongruous conditions in these cortical sites. In
      addition, patients in VS showed a delayed N400 in comparison with patients in MCS
      in incongruous condition. Secondly, a direct correlation was found between the
      clinical scales and the ERP modulation, in terms of peak amplitude and latency.
      Thus the present results were discussed taking into account the significance of
      N400 as a marker of semantic processes in patients with DOC. Secondly it was
      underlined that this cognitive covert process may be demonstrated also in
      patients who show significant impairment in overt behavior (as in VS or MCS).
      Finally it was suggested to use ERP measure to improve the diagnostic profile in
      cases of DOC. 

PMID- 26219658
TI  - A comparison of discrimination learning in touchscreen and 2-choice swim tank
      using an allelic series of Huntington's disease mice.
AB  - BACKGROUND: Progressive cognitive impairments are a major, debilitating symptom
      of neurodegenerative disorders such as Alzheimer's disease (AD) and Huntington's
      disease (HD). Developing treatments to slow or prevent cognitive decline is a key
      challenge for these fields. Unfortunately, preclinical therapeutic testing has
      not kept pace with molecular advances, and the methods for systematic cognitive
      testing in mice remain largely unchanged. Although higher throughput semi
      automated systems exist, the lack of a 'positive control' (i.e. a drug or
      treatment that works) makes it challenging to test their sensitivity and predict
      usefulness for preclinical drug testing. NEW METHOD: We used an allelic series of
      transgenic HD mice to test the sensitivity and flexibility of two cognitive
      testing systems; a semi-automated touchscreen system and a traditional water
      based task, the 2-choice swim tank. RESULTS: We found significant differences in
      performance of HD mice with different CAG repeats, with timing and severity of
      deficits dependent on CAG repeat length. We also found deficits in long-term
      memory retention that have not been reported previously. COMPARISON WITH EXISTING
      METHOD(S): Both systems were useful for detecting deficits, and were sensitive
      enough to detect small changes (10-20%) in cognitive performance. CONCLUSIONS:
      While the touchscreen system is more sensitive and can identify deficits up to 10
      weeks earlier than the 2-choice swim tank, both tests detected similar patterns
      of deficit progression in HD mice, regardless of CAG repeat length. Thus,
      although it has its limitations, the 2-choice swim tank remains a simple, cheap
      and accessible system for assessing cognitive function.

PMID- 26219659
TI  - Building a zebrafish toolkit for investigating the pathobiology of epilepsy and
      identifying new treatments for epileptic seizures.
AB  - Recent advances in genomics and genome sequencing technologies provide a wealth
      of DNA sequence data that sheds new light on the causes of epilepsy. Animal
      models help to elucidate the biological significance of such disease-associated
      DNA sequence variation by enabling functional relationships between disease
      genotypes and phenotypes to be defined. Here I review the unique combination of
      attributes that is allowing the zebrafish to play increasingly prominent roles in
      investigating the mechanisms underlying epilepsy and in discovering new drugs to
      treat this condition. New techniques for genome editing now allow the zebrafish
      genome to be engineered to recapitulate key elements of the patterns of genomic
      variation that are observed in epilepsy patients. Moreover, a sophisticated range
      of imaging technologies enables spatio-temporal patterns of neural activity to be
      visualised in the intact zebrafish nervous system with single-cell levels of
      resolution. These technologies, together with refined techniques for
      electrophysiological analysis and non-invasive modulation of specific neuronal
      circuit functions, allow the impacts of defined genetic variation on in vivo
      patterns of neural activity to be analysed in unprecedented depth. The
      pharmacological tractability of the zebrafish, and the amenability of its
      embryonic and larval stages to high throughput phenotype analysis, are also
      enabling advances in anti-epileptic drug discovery. Combining such
      pharmacological screening approaches with new tools for genome editing, live
      imaging, electrophysiology, conditional manipulation of circuit activity and
      behavioural analysis of zebrafish, could facilitate step changes in both
      understanding of epileptogenesis and in vivo discovery of new and improved anti
      epileptic drugs. 

PMID- 26219660
TI  - Abnormal septal convexity into the left ventricle occurs in subclinical
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Sarcomeric gene mutations cause hypertrophic cardiomyopathy (HCM). In
      gene mutation carriers without left ventricular (LV) hypertrophy (G + LVH-),
      subclinical imaging biomarkers are recognized as predictors of overt HCM,
      consisting of anterior mitral valve leaflet elongation, myocardial crypts,
      hyperdynamic LV ejection fraction, and abnormal apical trabeculation. Reverse
      curvature of the interventricular septum (into the LV) is characteristic of overt
      HCM. We aimed to assess LV septal convexity in subclinical HCM. METHODS:
      Cardiovascular magnetic resonance was performed on 36 G + LVH- individuals (31 +/
      14 years, 33 % males) with a pathogenic sarcomere mutation, and 36 sex and age
      matched healthy controls (33 +/- 12 years, 33 % males). Septal convexity (SCx)
      was measured in the apical four chamber view perpendicular to a reference line
      connecting the mid-septal wall at tricuspid valve insertion level and the apical
      right ventricular insertion point. RESULTS: Septal convexity was increased in G +
      LVH- compared to controls (maximal distance of endocardium to reference line: 5.0
      +/- 2.5 mm vs. 1.6 +/- 2.4 mm, p <= 0.0001). Expected findings occurred in G +
      LVH- individuals: longer anterior mitral valve leaflet (23.5 +/- 3.0 mm vs. 19.9
      +/- 3.1 mm, p <= 0.0001), higher relative wall thickness (0.31 +/- 0.05 vs. 0.29
      +/- 0.04, p <= 0.05), higher LV ejection fraction (70.8 +/- 4.3 % vs. 68.3 +/-
      4.4 %, p <= 0.05), and smaller LV end-systolic volume index (21.4 +/- 4.4 ml/m(2)
      vs. 23.7 +/- 5.8 ml/m(2), p <= 0.05). Other morphologic measurements (LV angles,
      sphericity index, and eccentricity index) were not different between G + LVH- and
      controls. CONCLUSIONS: Septal convexity is an additional previously undescribed
      feature of subclinical HCM.

PMID- 26219661
TI  - Evaluation of microbubble contrast agents for dynamic imaging with x-ray phase
      contrast.
AB  - X-rays are commonly used as a means to image the inside of objects opaque to
      visible light, as their short wavelength allows penetration through matter and
      the formation of high spatial resolution images. This physical effect has found
      particular importance in medicine where x-ray based imaging is routinely used as
      a diagnostic tool. Increasingly, however, imaging modalities that provide
      functional as well as morphological information are required. In this study the
      potential to use x-ray phase based imaging as a functional modality through the
      use of microbubbles that can be targeted to specific biological processes is
      explored. We show that the concentration of a microbubble suspension can be
      monitored quantitatively whilst in flow using x-ray phase contrast imaging. This
      could provide the basis for a dynamic imaging technique that combines the tissue
      penetration, spatial resolution, and high contrast of x-ray phase based imaging
      with the functional information offered by targeted imaging modalities. 

PMID- 26219662
TI  - Class II pentalogy of Cantrell.
AB  - BACKGROUND: Pentalogy of Cantrell is a rare syndrome, first described by Cantrell
      and co-workers in 1958. The syndrome is characterized by the presence of five
      major congenital defects involving the diaphragm, abdominal wall, the
      diaphragmatic pericardium, lower sternum and various congenital intra-cardiac
      abnormalities. The syndrome has never been reported in Tanzania, although may
      have been reported from other African countries. Survival rate of the complete
      form of pentalogy of Cantrell is as low as 20%, but recent studies have reported
      normal growth achieved by 6 years of age where corrective surgeries were done;
      showing that surgical repair early in life is essential for survival. CASE
      PRESENTATION: The African baby residing in Tanzania was referred from a district
      hospital on the second day of life. She was noted to have a huge omphalocele and
      ectopia cordis covered by a thin membrane, with bowels visible through the
      membrane and the cardiac impulse visible just below the epigastrium. Despite the
      physical anomaly, she appeared to saturate well in room air and had stable
      vitals. Her chest X-ray revealed the absence of the lower segments of the sternum
      and echocardiography showed multiple intra-cardiac defects. Based on these
      findings, the diagnosis of pentalogy of Cantrell was reached. On her fifth day of
      life, the neonate was noted to have signs of cardiac failure characterized by
      easy fatigability and restlessness during feeding. Cardiac failure treatment was
      initiated and she was discharged on parents' request on the second week of life.
      Due to inadequate facilities to undertake this complex corrective surgery,
      arrangements were being made to refer her abroad. In the meantime, her growth and
      development was satisfactory until the age of 9 months, when she ran out of the
      medications and succumbed to death. Her parents could no longer afford transport
      cost to attend the monthly clinic visits, where the infant was getting free
      medication refill. CONCLUSIONS: The case reported here highlights that in
      resource limited settings; poor outcome in infants with complex congenital
      anomalies is a function of multiple factors. However, we believe that surgery
      would have averted mortality in this 9-month-old female infant. We hope to be
      able to manage these cases better in future following the recent establishment of
      cardiac surgery facilities at Muhimbili National Hospital.

PMID- 26219663
TI  - Biomechanical evaluation of bone screw fixation with a novel bone cement.
AB  - BACKGROUND: Bone cement augmentation is commonly used to improve the fixation
      stability of orthopaedic implants in osteoporotic bone. The aim of this study was
      to evaluate the effect of novel bone cements on the stability of bone screw
      fixation by biomechanical testing and to compare them with a conventional
      Simplex((r))P bone cement and requirements of the standards. METHODS: Basic
      biomechanical properties were compared with standard tests. Adhesion of bone
      cements were tested with polished, glass blasted and corundum blasted stainless
      steel surfaces. Screw pullout testing with/without cement was carried out using a
      synthetic bone model and cancellous and cortical bone screws. RESULTS: All the
      tested bone cements fulfilled the requirements of the standard for biomechanical
      properties and improved the screw fixation stability. Even a threefold increase
      in shear and tensile strength was achieved with increasing surface roughness. The
      augmentation improved the screw pullout force compared to fixation without
      augmentation, 1.2-5.7 times depending on the cement and the screw type. The good
      biomechanical properties of novel bone cement for osteoporotic bone were
      confirmed by experimental testing. CONCLUSION: Medium viscosity of the bone
      cements allowed easy handling and well-controlled penetration of bone cement into
      osteoporotic bone. By proper parameters and procedures it is possible to achieve
      biomechanically stable fixation in osteoporotic bone. Based on this study, novel
      biostable bone cements are very potential biomaterials to enhance bone screw
      fixation in osteoporotic bone. Novel bone cement is easy to use without hand
      mixing using a dual syringe and thus makes it possibility to use it as required
      during the operation.

PMID- 26219664
TI  - Lymphomatoid papulosis: A cutaneous lymphoproliferative disorder in a patient on
      fingolimod for multiple sclerosis.
AB  - BACKGROUND: Fingolimod was the first oral disease-modifying treatment for
      relapsing-remitting multiple sclerosis. It has previously been associated with
      the development of lymphoma. OBJECTIVE: To describe a case of lymphomatoid
      papulosis, a CD30+ cutaneous lymphoproliferative disorder, in a patient taking
      fingolimod. METHODS: Case study. RESULTS: Our patient developed lymphomatoid
      papulosis 2 months after starting fingolimod. Histology confirmed the diagnosis.
      The drug was withdrawn. Resolution began only 2 days later. CONCLUSIONS:
      Lymphomatoid papulosis is a benign subtype of cutaneous T-cell lymphoma, but up
      to 20% of cases can transform to a malignant course. Patients on fingolimod and
      physicians caring for them should be mindful of the need to monitor the skin.

PMID- 26219665
TI  - Elevated Troponin Levels in Patients Without Acute Coronary Syndrome: What is the
      Real Diagnosis?

PMID- 26219666
TI  - Factors Contributing to the Low Rate of Surgical Revascularization in Spain.

PMID- 26219667
TI  - Comparing the effects of whole-body vibration to standard exercise in ambulatory
      people with Multiple Sclerosis: a randomised controlled feasibility study.
AB  - OBJECTIVES: This study aimed firstly to investigate the feasibility of the study
      protocol and outcome measures, secondly to obtain data in order to inform the
      power calculations for a larger randomised controlled trial, and finally to
      investigate if whole-body vibration (WBV) is more effective than the same
      duration and intensity of standard exercises (EXE) in people with Multiple
      Sclerosis (PwMS). DESIGN: Randomised controlled feasibility study. SETTING:
      Outpatient MS centre. SUBJECTS: Twenty seven PwMS (age mean (SD) 48.1 (11.2))
      with minimal gait impairments. INTERVENTIONS: Twelve weeks of WBV or standard
      EXE, three times weekly. MAIN MEASURES: Participants were measured with
      isokinetic muscle strength, vibration threshold, Timed Up and Go test (TUG), Mini
      BESTest (MBT), 6 Minute Walk test (6MWT), Multiple Sclerosis Impact Scale 29
      (MSIS 29), Modified Fatigue Impact Scale (MFIS) and Verbal Analogue scale for
      sensation (VAS) pre and post 12 week intervention. RESULTS: WBV intervention was
      found feasible with low drop-out rate (11.1%) and high compliance (90%). Data
      suggest that a sample of 52 in each group would be sufficient to detect a
      moderate effect size, with 80% power and 5% significance for 6 minute walk test.
      Large effect sizes in favour of standard exercise were found for vibration
      threshold at 5th metatarsophalangeal joint and heel (P=0.014, r= 0.5 and P=0.005,
      r=0.56 respectively). No between group differences were found for muscle
      strength, balance or gait (P>0.05). CONCLUSIONS: Data suggest that the protocol
      is feasible, there were no adverse effects. A trial including 120 people would be
      needed to detect an effect on walking endurance.

PMID- 26219668
TI  - A meta analysis of genome-wide association studies for limb bone lengths in four
      pig populations.
AB  - BACKGROUND: Limb bone length is an economically important trait in pigs, because
      it is negatively correlated with backfat thickness, and is also a determinant to
      the yield of hip and loin. Moreover, abnormal growth of the limb bone leads to
      leg structural weakness. Until now, the genetic architecture of the pig lime bone
      length remains poorly understood. The object of this study was to map genomic
      loci for limb bone length by genome-wide association study (GWAS) on 4 pig
      populations. RESULTS: We measured the lengths of five limb bones including
      scapula, humerus, ulna, femur and tibia that were dissected from the right-side
      carcass of 925, 331, 314 and 434 animals from White Duroc * Erhualian F2
      intercross, Erhualian, Laiwu and Sutai populations, respectively. We genotyped
      the 2004 pigs for 62,163 single nucleotide polymorphisms (SNPs) on the Porcine
      SNP60 BeadChip, and performed GWAS and a GWAS meta analysis in the 4 populations.
      In total, we identified 12 and 4 loci associated with the limb bone lengths at
      suggestive and genome-wide significant levels respectively, of which 4 loci were
      reported for the first time. The most prominent locus was identified in a 924-kb
      (kilo base pairs) linkage disequilibrium block on Sus Scrofa chromosome (SSC) 7,
      and High Mobility Group AT-hook 1 (HMGA1) appears to be a strong candidate gene
      in this region. Another promising locus is located in the middle of SSC4, and
      Pleiomorphic Adenoma Gene 1 (PLAG1) is a functionally plausible candidate gene
      underlying the locus. Because the lengths of the 5 limb bones are highly
      correlated to each other, most of significant loci were associated with all of
      the 5 traits; however, several loci showed specific effect on the length of one
      limb bone, such as the locus at the proximal end of SSC2 associated with only the
      scapula length. CONCLUSION: To our knowledge, this study was the first GWAS meta
      analysis for limb bone lengths in pigs. As expected, the meta analysis is more
      powerful to identify genomic loci. A total of 16 loci were identified in this
      study, including four novel loci. HMGA1 and PLAG1 are two appearing candidate
      genes for pig limb bone lengths, which warrant further investigations.

PMID- 26219669
TI  - Spatial, socio-economic, and ecological implications of incorporating minimum
      size constraints in marine protected area network design.
AB  - Marine protected areas (MPAs) are the cornerstone of most marine conservation
      strategies, but the effectiveness of each one partly depends on its size and
      distance to other MPAs in a network. Despite this, current recommendations on
      ideal MPA size and spacing vary widely, and data are lacking on how these
      constraints might influence the overall spatial characteristics, socio-economic
      impacts, and connectivity of the resultant MPA networks. To address this problem,
      we tested the impact of applying different MPA size constraints in English
      waters. We used the Marxan spatial prioritization software to identify a network
      of MPAs that met conservation feature targets, whilst minimizing impacts on
      fisheries; modified the Marxan outputs with the MinPatch software to ensure each
      MPA met a minimum size; and used existing data on the dispersal distances of a
      range of species found in English waters to investigate the likely impacts of
      such spatial constraints on the region's biodiversity. Increasing MPA size had
      little effect on total network area or the location of priority areas, but as MPA
      size increased, fishing opportunity cost to stakeholders increased. In addition,
      as MPA size increased, the number of closely connected sets of MPAs in networks
      and the average distance between neighboring MPAs decreased, which consequently
      increased the proportion of the planning region that was isolated from all MPAs.
      These results suggest networks containing large MPAs would be more viable for the
      majority of the region's species that have small dispersal distances, but
      dispersal between MPA sets and spill-over of individuals into unprotected areas
      would be reduced. These findings highlight the importance of testing the impact
      of applying different MPA size constraints because there are clear trade-offs
      that result from the interaction of size, number, and distribution of MPAs in a
      network. 

PMID- 26219671
TI  - Low-level antimicrobial resistance of Enterobacteriaceae isolated from the nares
      of pig-exposed persons.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E)
      have recently emerged in livestock and humans. Therefore, this study assessed the
      carriage of Enterobacteriaceae in the anterior nares and associated antimicrobial
      resistance in pig-exposed persons. Nasal swabs were enriched in non-selective
      broth and then plated on MacConkey and ESBL-selective agars. Species was
      confirmed by matrix-assisted laser-desorption ionization-time-of-flight mass
      spectrometry (MALDI-ToF MS). Antimicrobial susceptibility testing was performed
      according to European Committee on Antimicrobial Susceptibility Testing (EUCAST)
      guidelines. Of 114 pig-exposed persons tested, Enterobacteriaceae were detected
      in the nares of 76 (66.7%) participants. The predominant species were Proteus
      mirabilis (n = 17, 14.9%), Pantoea agglomerans (n = 13, 11.4%), Morganella
      morganii (n = 9, 7.9%), Citrobacter koseri (n = 9, 7.9%), Klebsiella pneumoniae,
      Escherichia coli and Proteus vulgaris (each n = 8, 7.0%). ESBL-E were not
      detected. Of all isolates tested, 3.4% were resistant against ciprofloxacin, 2.3%
      against gentamicin, 23.9% against trimethoprim-sulfamethoxazole and 44.3% against
      tigecycline. Despite the high prevalence of ESBL-E in livestock, pig-exposed
      persons did not carry ESBL-E in their nares. This finding is important, because
      colonization of the nasal reservoir might cause endogenous infections or
      facilitate transmission of ESBL-E in the general population. 

PMID- 26219670
TI  - Laparoscopic versus open gastrectomy for gastric cancer, a multicenter
      prospectively randomized controlled trial (LOGICA-trial).
AB  - BACKGROUND: For gastric cancer patients, surgical resection with en-bloc
      lymphadenectomy is the cornerstone of curative treatment. Open gastrectomy has
      long been the preferred surgical approach worldwide. However, this procedure is
      associated with considerable morbidity. Several meta-analyses have shown an
      advantage in short-term outcomes of laparoscopic gastrectomy compared to open
      procedures, with similar oncologic outcomes. However, it remains unclear whether
      the results of these Asian studies can be extrapolated to the Western population.
      In this trial from the Netherlands, patients with resectable gastric cancer will
      be randomized to laparoscopic or open gastrectomy. METHODS: The study is a non
      blinded, multicenter, prospectively randomized controlled superiority trial.
      Patients (>=18 years) with histologically proven, surgically resectable (cT1-4a,
      N0-3b, M0) gastric adenocarcinoma and European Clinical Oncology Group
      performance status 0, 1 or 2 are eligible to participate in the study after
      obtaining informed consent. Patients (n = 210) will be included in one of the ten
      participating Dutch centers and are randomized to either laparoscopic or open
      gastrectomy. The primary outcome is postoperative hospital stay (days). Secondary
      outcome parameters include postoperative morbidity and mortality, oncologic
      outcomes, readmissions, quality of life and cost-effectiveness. DISCUSSION: In
      this randomized controlled trial laparoscopic and open gastrectomy are compared
      in patients with resectable gastric cancer. It is expected that laparoscopic
      gastrectomy will result in a faster recovery of the patient and a shorter
      hospital stay. Secondly, it is expected that laparoscopic gastrectomy will be
      associated with a lower postoperative morbidity, less readmissions, higher cost
      effectiveness, better postoperative quality of life, but with similar mortality
      and oncologic outcomes, compared to open gastrectomy. The study started on 1
      December 2014. Inclusion and follow-up will take 3 and 5 years respectively.
      Short-term results will be analyzed and published after discharge of the last
      randomized patient. TRIAL REGISTRATION: NCT02248519.

PMID- 26219672
TI  - A tsetse and tabanid fly survey of African great apes habitats reveals the
      presence of a novel trypanosome lineage but the absence of Trypanosoma brucei.
AB  - Tsetse and tabanid flies transmit several Trypanosoma species, some of which are
      human and livestock pathogens of major medical and socioeconomic impact in
      Africa. Recent advances in molecular techniques and phylogenetic analyses have
      revealed a growing diversity of previously unidentified tsetse-transmitted
      trypanosomes potentially pathogenic to livestock and/or other domestic animals as
      well as wildlife, including African great apes. To map the distribution,
      prevalence and co-occurrence of known and novel trypanosome species, we analyzed
      tsetse and tabanid flies collected in the primary forested part of the Dzanga
      Sangha Protected Areas, Central African Republic, which hosts a broad spectrum of
      wildlife including primates and is virtually devoid of domestic animals.
      Altogether, 564 tsetse flies and 81 tabanid flies were individually screened for
      the presence of trypanosomes using 18S rRNA-specific nested PCR. Herein, we
      demonstrate that wildlife animals are parasitized by a surprisingly wide range of
      trypanosome species that in some cases may circulate via these insect vectors.
      While one-third of the examined tsetse flies harbored trypanosomes either from
      the Trypanosoma theileri, Trypanosoma congolense or Trypanosoma simiae complex,
      or one of the three new members of the genus Trypanosoma (strains 'Bai',
      'Ngbanda' and 'Didon'), more than half of the tabanid flies exclusively carried
      T. theileri. To establish the putative vertebrate hosts of the novel trypanosome
      species, we further analyzed the provenance of blood meals of tsetse flies. DNA
      individually isolated from 1033 specimens of Glossina spp. and subjected to high
      throughput library-based screening proved that most of the examined tsetse flies
      engorged on wild ruminants (buffalo, sitatunga, bongo), humans and suids.
      Moreover, they also fed (albeit more rarely) on other vertebrates, thus providing
      indirect but convincing evidence that trypanosomes can be transmitted via these
      vectors among a wide range of warm- and cold-blooded hosts. 

PMID- 26219673
TI  - Surveying the lipogenesis landscape in Yarrowia lipolytica through understanding
      the function of a Mga2p regulatory protein mutant.
AB  - Lipogenic organisms represent great starting points for metabolic engineering of
      oleochemical production. While previous engineering efforts were able to
      significantly improve lipid production in Yarrowia lipolytica, the lipogenesis
      landscape, especially with respect to regulatory elements, has not been fully
      explored. Through a comparative genomics and transcriptomics approach, we
      identified and validated a mutant mga2 protein that serves as a regulator of
      desaturase gene expression and potent lipogenesis factor. The resulting strain is
      enriched in unsaturated fatty acids. Comparing the underlying mechanism of this
      mutant to other previously engineered strains suggests that creating an imbalance
      between glycolysis and the TCA cycle can serve as a driving force for lipogenesis
      when combined with fatty acid catabolism overexpressions. Further comparative
      transcriptomics analysis revealed both distinct and convergent rewiring
      associated with these different genotypes. Finally, by combining metabolic
      engineering targets, it is possible to further engineer a strain containing the
      mutant mga2 gene to a lipid production titer of 25g/L. 

PMID- 26219674
TI  - (13)C-metabolic flux analysis of co-cultures: A novel approach.
AB  - In this work, we present a novel approach for performing (13)C metabolic flux
      analysis ((13)C-MFA) of co-culture systems. We demonstrate for the first time
      that it is possible to determine metabolic flux distributions in multiple species
      simultaneously without the need for physical separation of cells or proteins, or
      overexpression of species-specific products. Instead, metabolic fluxes for each
      species in a co-culture are estimated directly from isotopic labeling of total
      biomass obtained using conventional mass spectrometry approaches such as GC-MS.
      In addition to determining metabolic fluxes, this approach estimates the relative
      population size of each species in a mixed culture and inter-species metabolite
      exchange. As such, it enables detailed studies of microbial communities including
      species dynamics and interactions between community members. The methodology is
      experimentally validated here using a co-culture of two E. coli knockout strains.
      Taken together, this work greatly extends the scope of (13)C-MFA to a large
      number of multi-cellular systems that are of significant importance in
      biotechnology and medicine. 

PMID- 26219675
TI  - Reconciling surveillance systems with limited resources: an evaluation of passive
      surveillance for rabies in an endemic setting.
AB  - Surveillance systems for rabies in endemic regions are often subject to severe
      constraints in terms of resources. The World Organisation for Animal Health (OIE)
      and the World Health Organisation (WHO) propose the use of an active surveillance
      system to substantiate claims of disease freedom, including rabies. However, many
      countries do not have the resources to establish active surveillance systems for
      rabies and the testing of dead dogs poses logistical challenges. This paper
      explores the potential of using a scenario tree model parameterised with data
      collected via questionnaires and interviews to estimate the sensitivity of
      passive surveillance, assessing its potential as a viable low-cost alternative to
      active surveillance systems. The results of this explorative study illustrated
      that given a large enough sample size, in this case the entire population of
      Colombo City, the sensitivity of passive surveillance can be 100% even at a low
      disease prevalence (0.1%), despite the low sensitivity of individual surveillance
      components (mean values in the range 4.077*10(-5)-1.834*10(-3) at 1% prevalence).
      In addition, logistic regression was used to identify factors associated with
      increased recognition of rabies in dogs and reporting of rabies suspect dogs.
      Increased recognition was observed amongst dog owners (OR 3.8 (CI, 1.3-10.8)),
      people previously bitten by dogs (OR 5.9 (CI, 2.2-15.9)) and people who believed
      they had seen suspect dogs in the past (OR 4.7 (CI, 1.8-12.9)). Increased
      likelihood of reporting suspect dogs was observed amongst dog owners (OR 5.3 (CI,
      1.1-25)). Further work is required to validate the data collection tool and the
      assumptions made in the model with respect to sample size in order to develop a
      robust methodology for evaluating passive rabies surveillance. 

PMID- 26219676
TI  - Bosnian, Iraqi, and Somali Refugee Women Speak: A Comparative Qualitative Study
      of Refugee Health Beliefs on Preventive Health and Breast Cancer Screening.
AB  - INTRODUCTION: The low uptake of preventive services in disadvantaged communities
      is a continuing challenge to public health. Women refugee communities are
      particularly vulnerable populations, and disparities in both preventive care and
      breast cancer screening have been documented sparsely. The objective of this
      qualitative study was to explore Bosnian, Iraqi, and Somali women refugees'
      beliefs about preventive care and breast cancer screening to inform future
      community interventions and best practices. METHODS: In an urban community health
      center, 57 interviews with Bosnian, Somali, and Iraqi women refugees were
      conducted by native language speakers. Interview transcripts were coded and
      analyzed according to best practices for thematic and content analysis. The
      responses of three groups were compared. FINDINGS: Similarities across
      participants included barriers to care such as fear of pain and diagnosis,
      modesty, and work and childcare commitments; facilitative factors such as
      outreach efforts, appointment reminders, and personal contact from health
      providers; perceptions of how the American medical infrastructure compared with
      inadequacies in their home countries; and positive attitude toward U.S. health
      professionals. Differences that emerged among groups were: varying degrees of
      medical exposure to doctors in home countries, the impact of war on health
      systems; and understanding preventive breast care. CONCLUSION: Taken together,
      duration of time in United States and prior exposure to Western medicine account
      for differences in refugee women's knowledge of preventive care. Understanding
      population-specific health beliefs, health information, and behavior are crucial
      for designing tailored prevention programs for refugee women.

PMID- 26219677
TI  - Geographic Access to Mammography and Its Relationship to Breast Cancer Screening
      and Stage at Diagnosis: A Systematic Review.
AB  - INTRODUCTION: A review was conducted to summarize the current evidence and gaps
      in the literature on geographic access to mammography and its relationship to
      breast cancer-related outcomes. METHODS: Ovid, Medline, and PubMed were searched
      for articles published between January 1, 2000, and April 1, 2013, using Medical
      Subject Headings and key terms representing geographic accessibility and breast
      cancer-related outcomes. Owing to a paucity of breast cancer treatment and
      mortality outcomes meeting the criteria (N = 6), outcomes were restricted to
      breast cancer screening and stage at diagnosis. Studies included one or more of
      the following types of geographic accessibility measures: capacity, density,
      distance, and travel time. Study findings were grouped by outcome and type of
      geographic measure. RESULTS: Twenty-one articles met the inclusion criteria.
      Fourteen articles included stage at diagnosis as an outcome, five included
      mammography use, and two included both. Geographic measures of mammography
      accessibility varied widely across studies. Findings also varied, but most
      articles found either increased geographic access to mammography associated with
      increased use and decreased late-stage at diagnosis or no association.
      CONCLUSION: The gaps and methodologic heterogeneity in the literature to date
      limit definitive conclusions about an underlying association between geographic
      mammography access and breast cancer-related outcomes. Future studies should
      focus on the development and application of more precise and consistent measures
      of geographic access to mammography.

PMID- 26219679
TI  - The impact of CLAUDIN-1 on follicular thyroid carcinoma aggressiveness.
AB  - CLAUDIN-1 belongs to the family of transmembrane tight junction proteins
      tightening the paracellular cleft of epithelial cells. In human malignancies,
      CLAUDIN-1 is often dysregulated and located in subcellular compartments,
      particularly in the nucleus where it may influence cellular behaviour. Here, we
      studied CLAUDIN-1 in relation to the biological characteristics of follicular
      thyroid carcinoma (FTC). CLAUDIN-1 immuno-staining showed loss of membrane
      expression and increased nuclear CLAUDIN-1 localization in FTC metastases.
      CLAUDIN-1 function was further investigated in two different follicular thyroid
      carcinoma cell lines: FTC-133 isolated from a regional lymph node metastasis and
      FTC-238 derived from a lung metastasis. In both cell lines CLAUDIN-1 expression
      was demonstrated in the cell nuclei with a significantly higher protein
      expression in FTC-238 compared to FTC-133 cells. Interestingly, in vitro scratch
      assay revealed enriched nuclear CLAUDIN-1 expression near the scratch.
      Furthermore, the increase of the pathogenic character of FTC-133 cells by RASV12
      transfection was associated with elevated CLAUDIN-1 expression and enhanced cell
      migration, invasion and proliferation. Likewise over-expression of nuclear
      CLAUDIN-1 in FTC-133 cells resulted in increased cell migration and invasion.
      Conversely, CLAUDIN-1 downregulation in FTC-238 cells by siRNA resulted in
      decreased cell migration and invasion and was accompanied by reduced phosphoPKC
      expression. Moreover, activation and inhibition of PKC resulted in CLAUDIN-1 up-
      and downregulation in FTC cells respectively. These data suggest an impact of
      CLAUDIN-1 on follicular thyroid carcinoma aggressiveness, which could potentially
      be influenced by PKC activity. 

PMID- 26219678
TI  - The role of proto-oncogene GLI1 in pituitary adenoma formation and cell survival
      regulation.
AB  - The Hedgehog (Hh) pathway is an important regulator of early tissue patterning
      and stem cell propagation. It was found to be aberrantly activated in numerous
      types of human cancer and might be relevant in cancer stem cells. The
      identification of adult stem cells in the pituitary raised the question if tumor
      initiating cells and Hh signaling are involved in pituitary adenoma formation.
      The present study aimed at the evaluation of Hh signaling in relation to stem
      cell and cell cycle markers in 30 human pituitary adenomas and in cultured murine
      adenoma cells. Therefore, expression levels of components of the Hh pathway, stem
      cell marker SOX2, cell cycle regulator tumor-protein 53 (TP53), proliferation
      marker Ki67 (MKI67) and superoxide dismutase 1 (SOD1) were evaluated in 30 human
      pituitary adenomas in comparison to control tissue. Modulation of cell function
      and target gene expression by the inhibition and activation of the Hh pathway
      were studied in murine adenoma cells. We show that transcription factor glioma
      associated oncogene 1 (GLI1) is overexpressed in 87% of all pituitary adenomas.
      The expression of GLI1 significantly correlated with that of SOX2, TP53, MKI67
      and SOD1. Inhibition of GLI1 resulted in the downregulation of the above genes
      and severe cell death in mouse adenoma cells. On the other hand, activation of
      the Hh pathway increased cell viability and target gene expression. In
      conclusion, our findings point toward an alternative, ligand-independent Hh
      pathway activation with GLI1 playing a major role in the cell survival of
      pituitary adenoma cells. 

PMID- 26219680
TI  - Training Substance Use Disorder Counselors in Cognitive Behavioral Therapy for
      Depression: Development and Initial Exploration of an Online Training Program.
AB  - INTRODUCTION: Evidence based psychotherapies (EBPs) remain underutilized. Models
      for EBP training and implementation that are cost-effective, minimally
      disruptive, and sufficiently flexible are needed. Internet-based technology is a
      promising platform, but questions remain about how this technology can address
      the barriers to implementation. We developed and examined the implementation of
      an online training for the Building Recovery by Improving Goals, Habits, and
      Thoughts (BRIGHT) intervention-a manualized, sixteen-session group depression
      treatment for individuals with substance use disorders (SUDs). We explored the
      feasibility of replacing in-person BRIGHT training with a self-paced, online
      training. METHODS: A highly partnered and iterative process was followed to
      translate the written BRIGHT manual and associated didactic training materials
      into a media rich, interactive, and detailed (12-16 h) online training.
      Subsequently, 8 volunteer counselors across 7 Veterans' Affairs SUD programs
      completed the training. Semi-structured interviews focused on the counselors'
      experiences and their plans for implementing BRIGHT groups. A template approach,
      using a mixture of deductive and inductive coding, was used for data analyses.
      FINDINGS: The most important barrier to completing training was a lack of
      protected time. Most counselors were not afforded protected time and reported a
      sometimes frustrating and fragmented training experience. Many used personal time
      at work and at home to complete the work. Facilitators to completing the training
      included positive reactions/attitudes towards the training modules, supervisor
      support, counselor dedication, and strong beliefs supporting providing services
      for depression. Many counselors were also concerned about the feasibility of
      fitting 16 group sessions (2h each) into their program's clinical schedule, but
      many had devised potential solutions or "work-arounds" to accommodate or
      approximate the recommended treatment course (e.g., using lunch times, reducing
      some content/exercises). CONCLUSION: This work contributes to the literature on
      implementation of complex EBPs and addresses the strengths and limitations of web
      based technologies in supporting the implementation of EBPs.

PMID- 26219681
TI  - Longitudinal Examination of Medical Staff Utilization in Substance Use Disorder
      Treatment Organizations.
AB  - This study examined changes in utilization of medical staff within organizations
      specializing in treatment of patients with substance use disorder (SUD) at two
      points in time (2007 and 2010). Utilization was calculated as the number of hours
      paid weekly for psychiatrists, physicians, nurses, and other medical staff
      working as employees or on contract. Study data come from a longitudinal national
      sample of 274 substance use disorder treatment centers. Average utilization of
      medical staff by these SUD treatment organizations increased by 26% from 2007 to
      2010. The results showed that growing SUD treatment centers that obtained more
      referrals from health care providers, used case managers to coordinate
      comprehensive approaches to patient care, provided medication assisted treatment
      (MAT), and that were connected more closely with hospitals made increased use of
      medical staff over the 2007-2010 period. In 2010, these organizations seem to
      have been moving in directions consistent with trends forecasted for the SUD
      treatment environment after implementation of the Affordable Care Act. 

PMID- 26219682
TI  - Direct identification of major Gram-negative pathogens in respiratory specimens
      by respiFISH(r) HAP Gram (-) Panel, a beacon-based FISH methodology.
AB  - Rapid detection of microorganisms in respiratory specimens is of paramount
      importance to drive the proper antibiotic regimen to prevent complications and
      transmission of infections. In the present study, the respiFISH(r) HAP Gram (-)
      Panel (miacom diagnostics GmbH, Duesseldorf, Germany) for the etiological
      diagnosis of hospital-acquired pneumonia was compared with the traditional
      culture method for the detection of major Gram-negative pathogens in respiratory
      specimens. respiFISH(r) combined the classical fluorescence in situ hybridization
      (FISH) technology with fluorescence-labeled DNA molecular beacons as probes. From
      September 2011 to January 2012, 165 samples were analyzed: the sensitivity and
      specificity were 94.39 and 87.93%, respectively. Only six pathogens (3.6%) were
      not identified with respiFISH(r), while seven specimens (3%) provided false
      positive results. This beacon-based identification shortens the time to result by
      at least one work day, providing species-level identification within half an
      hour. Considering the high sensitivity and specificity and the significant time
      saving, the introduction of bbFISH(r) assays could effectively complement
      traditional systems in microbiology laboratories.

PMID- 26219683
TI  - Revisiting the Plant's Dilemma.

PMID- 26219684
TI  - The International Clinical Epidemiology Network increases capacity for clinical
      epidemiology research in Jamaica.

PMID- 26219685
TI  - Trophic structure of polychaetes around an offshore gas platform.
AB  - The distribution of polychaetes associated with an offshore gas platform built on
      a muddy-sandy bottom in the northern Adriatic Sea was investigated with emphasis
      on their feeding structure. Polychaete species were collected at different
      distances from the rig using a Van Veen grab. Assessment of the polychaete
      community and trophic groups for impacts related to the presence of the platform
      demonstrated significantly different abundances at rising distances from the rig.
      The present findings highlight an effect of the rig on the spatial distribution
      of polychaete assemblages. Even though the effects of gas platforms on
      surrounding benthic communities have been investigated in the Adriatic Sea, no
      studies have addressed the distribution of polychaete trophic groups along a
      gradient based on distance from the rig. 

PMID- 26219686
TI  - The performance of biomass-based AMBI in lagoonal ecosystems.
AB  - We studied the performance of the AZTI Marine Biotic Index AMBI manipulating
      input data collected from lagoonal ecosystems. Our data set consisted of
      macrofaunal abundance and biomass counts gathered at a variety of sites at which
      the disturbance status was known. Input data were also manipulated using a set of
      transformations of increasing severity. Biotic indices were calculated using raw
      and transformed abundance, biomass and production. Among the three categories of
      AMBI-based indices, medium transformation of data gave the highest correlation
      with pressures. However, increasing the severity of transformation generally
      resulted in a decrease of the correlation with environmental factors. The
      relative importance of ecological groups changed when using abundance or biomass,
      sometimes leading to an improved ecological status classification. Being biomass
      and production more ecologically relevant than abundance, using them to derive
      AMBI-based new indices seems intriguing, at least in lagoonal waters, where the
      community is naturally disturbed and dominated by opportunists. 

PMID- 26219687
TI  - Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European
      consensus-based interdisciplinary guideline.
AB  - Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in
      Caucasian populations, accounting for 20% of all cutaneous malignancies. A unique
      collaboration of multi-disciplinary experts from the European Dermatology Forum
      (EDF), the European Association of Dermato-Oncology (EADO) and the European
      Organization of Research and Treatment of Cancer (EORTC) was formed to make
      recommendations on cSCC diagnosis and management, based on a critical review of
      the literature, existing guidelines and the expert's experience. The diagnosis of
      cSCC is primarily based on clinical features. A biopsy or excision and histologic
      confirmation should be performed in all clinically suspicious lesions in order to
      facilitate the prognostic classification and correct management of cSCC. The
      first line treatment of cutaneous SCC is complete surgical excision with
      histopathological control of excision margins. The EDF-EADO-EORTC consensus group
      recommends a standardised minimal margin of 5 mm even for low-risk tumours. For
      tumours, with histological thickness of >6 mm or in tumours with high risk
      pathological features, e.g. high histological grade, subcutaneous invasion,
      perineural invasion, recurrent tumours and/or tumours at high risk locations an
      extended margin of 10 mm is recommended. As lymph node involvement by cSCC
      increases the risk of recurrence and mortality, a lymph node ultrasound is highly
      recommended, particularly in tumours with high-risk characteristics. In the case
      of clinical suspicion or positive findings upon imaging, a histologic
      confirmation should be sought either by fine needle aspiration or by open lymph
      node biopsy. In large infiltrating tumours with signs of involvement of
      underlying structures, additional imaging tests, such as CT or MRI imaging may be
      required to accurately assess the extent of the tumour and the presence of
      metastatic spread. Current staging systems for cSCC are not optimal, as they have
      been developed for head and neck tumours and lack extensive validation or
      adequate prognostic discrimination in certain stages with heterogeneous outcome
      measures. Sentinel lymph node biopsy has been used in patients with cSCC, but
      there is no conclusive evidence of its prognostic or therapeutic value. In the
      case of lymph node involvement by cSCC, the preferred treatment is a regional
      lymph node dissection. Radiation therapy represents a fair alternative to surgery
      in the non-surgical treatment of small cSCCs in low risk areas. It generally
      should be discussed either as a primary treatment for inoperable cSCC or in the
      adjuvant setting. Stage IV cSCC can be responsive to various chemotherapeutic
      agents; however, there is no standard regimen. EGFR inhibitors such as cetuximab
      or erlotinib, should be discussed as second line treatments after mono- or
      polychemotherapy failure and disease progression or within the framework of
      clinical trials. There is no standardised follow-up schedule for patients with
      cSCC. A close follow-up plan is recommended based on risk assessment of
      locoregional recurrences, metastatic spread or development of new lesions.

PMID- 26219688
TI  - Trends in survival for teenagers and young adults with cancer in the UK 1992
      2006.
AB  - BACKGROUND: Although relatively rare, cancer in teenagers and young adults (TYA)
      is the most common disease-related cause of death and makes a major contribution
      to years of life lost in this age group. There is a growing awareness of the
      distinctive needs of this age group and drive for greater understanding of how
      outcomes can be improved. We present here the latest TYA survival trends data for
      the United Kingdom (UK). METHODS: Using national cancer registry data, we
      calculated five-year relative survival for all 15-24 year olds diagnosed with
      cancer or a borderline/benign CNS tumour in the UK during the periods 1992-1996,
      1997-2001 and 2002-2006. We analysed trends in survival for all cancers combined
      and for eighteen specified groups that together represent the majority of TYA
      cancers. We compared our data with published data for Europe, North America and
      Australia. RESULTS: Five-year survival for all cancers combined increased from
      75.5% in 1992-1996 to 82.2% in 2002-2006 (P<0.001). Statistically significant
      improvements were seen for all disease groups except osteosarcoma,
      rhabdomyosarcoma, non-gonadal and ovarian germ cell tumours and ovarian and
      thyroid carcinomas. During the earliest time period, females had significantly
      better survival than males for five of the twelve non-gender-specific disease
      groups. By the latest period, only melanomas and non-rhabdomyosarcoma soft tissue
      sarcomas had differential survival by gender. Survival in the UK for the most
      recent period was generally similar to other comparable countries. CONCLUSION:
      Five-year survival has improved considerably in the UK for most cancer types. For
      some disease groups, there has been little progress, either because survival
      already approaches 100% (e.g. thyroid carcinomas) or, more worryingly for some
      cancers with poor outcomes, because they remain resistant to existing therapy
      (e.g. rhabdomyosarcoma). In addition, for a number of specific cancer types and
      for cancer as a whole males continue to have worse outcomes than females.

PMID- 26219689
TI  - Endobronchial Valves for Challenging Air Leaks.
AB  - BACKGROUND: Prolonged air leaks may result in increased morbidity and mortality.
      Endobronchial valves have been used as a nonoperative treatment. We evaluated the
      efficacy of endobronchial valves at achieving chest tube removal and hospital
      discharge for air leaks resulting from varied etiologies. METHODS: All
      consecutive patients undergoing endobronchial valve placement for persistent air
      leak were evaluated by a multidisciplinary team at a single institution. Those
      receiving valves underwent bronchoscopy with balloon occlusion to identify
      airways contributing to the leak. After airway sizing, unidirectional
      endobronchial valves were deployed. RESULTS: During an 18-month period, 21
      patients underwent 24 valve placement procedures; 88 valves were placed (median,
      3; mean, 3.6; range, 1 to 12). Patient age range was 16 months to 70 years. The
      underlying cause of persistent air leak was postoperative (n = 8), pneumothorax
      (n = 11), cavitary lung infection (n = 3), and postpneumonectomy bronchopleural
      fistula (n = 2). There were no valve-related complications during placement,
      dwell time, or removal. Three patients died as a result of their underlying
      disease, unrelated to valves. Of those with chest tubes who survived and were
      discharged, all had successful removal of their chest tubes. Median duration to
      chest tube removal after initial valve placement was 15 days (mean, 21 days;
      range, 0 to 86 days). Median length of stay after final valve placement was 5
      days (mean, 15 days; range, 0 to 196 days). CONCLUSIONS: Challenging air leaks
      often occur in medically compromised patients. They may persist despite multiple
      interventions. Endobronchial valves offer minimally invasive management. Time to
      chest tube removal and length of stay are variable, frequently because of
      clinical status and underlying disease.

PMID- 26219690
TI  - Assessment of Thoracic Endografting Operative Mortality Risk Score: Development
      and Validation in 2,000 Patients.
AB  - BACKGROUND: In this study we derive and validate a composite risk index termed
      the Assessment of Thoracic Endografting Operative Mortality, or ATOM, risk score.
      METHODS: All thoracic endovascular aortic repairs (TEVAR) in the American College
      of Surgeons National Surgical Quality Improvement Project (NSQIP) between 2005
      and 2012 were identified. The primary outcome was operative mortality. After
      evaluating the association of over 60 preoperative variables and operative
      mortality in univariate analysis, a multivariable model was developed.
      Significant risk factors were assigned points equivalent to their odds ratio
      rounded to the nearest whole integer in the final multivariable model. RESULTS:
      Overall, 1,981 patients comprised the study population, including 1,486 (75.0%)
      in the derivation and 495 (25.0%) in the validation cohort. There were 173 (8.7%)
      operative mortalities. A 30-point risk score incorporating 10 risk factors was
      generated and found to be highly predictive of operative mortality in the
      derivation (odds ratio [OR] 1.36, p < 0.001) and validation cohorts (OR 1.24, p <
      0.001). The models used to create and validate the ATOM score were robust (C
      indices 0.84 and 0.83, respectively). There was strong correlation between
      predicted mortality rates based on the derivation cohort and actual mortality
      rates in the validation cohort (r = 0.75, p < 0.001). Operative mortality based
      on low (ATOM < 5), moderate (ATOM 5 to 9), and high risk (ATOM >= 10) was 1.3%,
      6.6%, and 24.0%, respectively (p < 0.001). Higher ATOM scores also correlated
      with higher complication rates and longer hospital stays. CONCLUSIONS: The ATOM
      score is a significant predictor of operative mortality in TEVAR and can be used
      for preoperative risk stratification.

PMID- 26219691
TI  - Band structure engineering via piezoelectric fields in strained anisotropic
      CdSe/CdS nanocrystals.
AB  - Strain in colloidal heteronanocrystals with non-centrosymmetric lattices presents
      a unique opportunity for controlling optoelectronic properties and adds a new
      degree of freedom to existing wavefunction engineering and doping paradigms. We
      synthesized wurtzite CdSe nanorods embedded in a thick CdS shell, hereby
      exploiting the large lattice mismatch between the two domains to generate a
      compressive strain of the CdSe core and a strong piezoelectric potential along
      its c-axis. Efficient charge separation results in an indirect ground-state
      transition with a lifetime of several microseconds, almost one order of magnitude
      longer than any other CdSe/CdS nanocrystal. Higher excited states recombine
      radiatively in the nanosecond time range, due to increasingly overlapping excited
      state orbitals. kp calculations confirm the importance of the anisotropic shape
      and crystal structure in the buildup of the piezoelectric potential. Strain
      engineering thus presents an efficient approach to highly tunable single- and
      multiexciton interactions, driven by a dedicated core/shell nanocrystal design. 

PMID- 26219692
TI  - Editorial Commentary: Oral Polio Vaccine at Birth.

PMID- 26219693
TI  - Host-Directed Therapies for Tackling Multi-Drug Resistant Tuberculosis: Learning
      From the Pasteur-Bechamp Debates.
AB  - Tuberculosis remains a global emergency causing an estimated 1.5 million deaths
      annually. For several decades the major focus of tuberculosis treatment has been
      on antibiotic development targeting Mycobacterium tuberculosis. The lengthy
      tuberculosis treatment duration and poor treatment outcomes associated with multi
      drug resistant tuberculosis (MDR-TB) are of major concern. The sparse new
      tuberculosis drug pipeline and widespread emergence of MDR-TB signal an urgent
      need for more innovative interventions to improve treatment outcomes. Building on
      the historical Pasteur-Bechamp debates on the role of the "microbe" vs the "host
      internal milieu" in disease causation, we make the case for parallel investments
      into host-directed therapies (HDTs). A range of potential HDTs are now available
      which require evaluation in randomized controlled clinical trials as adjunct
      therapies for shortening the duration of tuberculosis therapy and improving
      treatment outcomes for drug-susceptible tuberculosis and MDR-TB. Funder
      initiatives that may enable further research into HDTs are described. 

PMID- 26219694
TI  - The Effect of Oral Polio Vaccine at Birth on Infant Mortality: A Randomized
      Trial.
AB  - BACKGROUND: Routine vaccines may have nonspecific effects on mortality. An
      observational study found that OPV given at birth (OPV0) was associated with
      increased male infant mortality. We investigated the effect of OPV0 on infant
      mortality in a randomized trial in Guinea-Bissau. METHODS: A total of 7012
      healthy normal-birth-weight neonates were randomized to BCG only (intervention
      group) or OPV0 with BCG (usual practice). All children were to receive OPV with
      pentavalent vaccine (diphtheria, tetanus, pertussis, Haemophilus influenzae type
      b, and hepatitis B) at 6, 10, and 14 weeks of age. Seven national OPV campaigns
      were also conducted during the trial period. Children were followed to age 12
      months. We used Cox regression to calculate hazard ratios (HRs) for mortality.
      RESULTS: The trial contradicted the original hypothesis about OPV0 increasing
      male infant mortality. Within 12 months, 73 children in the BCG + OPV group and
      87 children in the BCG-only group died, all from infectious diseases. Comparing
      BCG + OPV0 vs BCG only, the HR was 0.83 (95% confidence interval [CI], .61-1.13):
      0.72 (95% CI, .47-1.10) in boys and 0.97 (95% CI, .61-1.54) in girls. For
      children enrolled within the first 2 days of life, the HR for BCG + OPV0 vs BCG
      only was 0.58 (95% CI, .38-.90). From enrollment until the time of OPV campaigns,
      the HR was 0.68 (95% CI, .45-1.00), the beneficial effect being separately
      significant for males (0.55 [95% CI, .32-.95]). CONCLUSIONS: This is the only
      randomized trial of the effect of OPV0 on mortality. OPV0 may be associated with
      nonspecific protection against infectious disease mortality, particularly when
      given early in life. There are reasons to monitor mortality when OPV is being
      phased out. CLINICAL TRIALS REGISTRATION: NCT00710983.

PMID- 26219695
TI  - Association of immune response to endothelial cell growth factor with early
      disseminated and late manifestations of Lyme disease but not posttreatment Lyme
      disease syndrome.
AB  - Endothelial cell growth factor has been recently proposed as a potential
      autoantigen in manifestations of Lyme disease that are thought to involve immune
      mediated mechanisms. Our findings indicate that a humoral immune response to this
      protein is not associated with posttreatment Lyme disease syndrome. 

PMID- 26219696
TI  - Comparison of Ultrasound Corticomedullary Strain with Doppler Parameters in
      Assessment of Renal Allograft Interstitial Fibrosis/Tubular Atrophy.
AB  - To compare the capability of ultrasound strain and Doppler parameters in the
      assessment of renal allograft interstitial fibrosis/tubular atrophy (IF/TA), we
      prospectively measured ultrasound corticomedullary strain (strain) and intra
      renal artery Doppler end-diastolic velocity (EDV), peak systolic velocity (PSV)
      and resistive index (RI) in 45 renal transplant recipients before their kidney
      biopsies. We used 2-D speckle tracking to estimate strain, the deformation ratio
      of renal cortex to medulla produced by external compression using the ultrasound
      transducer. We also measured Doppler EDV, PSV and RI at the renal allograft inter
      lobar artery. Using the Banff scoring system for renal allograft IF/TA, 45
      patients were divided into the following groups: group 1 with <=5% (n = 12)
      cortical IF/TA; group 2 with 6%-25% (n = 12); group 3 with 26%-50% (n = 11); and
      group 4 with >50% (n = 10). We performed receiver operating characteristic curve
      analysis to test the accuracy of these ultrasound parameters and duration of
      transplantation in determining >26% cortical IF/TA. In our results, strain was
      statistically significant in all paired groups (all p < 0.005) and inversely
      correlated with the grade of cortical IF/TA (p < 0.001). However, the difference
      in PSV and EDV was significant only between high-grade (>26%, including 26%-50%
      and >50%) and low-grade (<=25%, including <5% and 6%-25%) cortical IF/TA (p <
      0.001). RI did not significantly differ in any paired group (all p > 0.05). The
      areas under the receiver operating characteristic curve for strain, EDV, PSV, RI
      and duration of transplantation in determining >26% cortical IF/TA were 0.99,
      0.94, 0.88, 0.52 and 0.92, respectively. Our results suggest that
      corticomedullary strain seems to be superior to Doppler parameters and duration
      of transplantation in assessment of renal allograft cortical IF/TA.

PMID- 26219698
TI  - Prevalence and correlates of body image dissatisfaction in postmenopausal women.
AB  - Dissatisfaction with one's body image is widespread and can have serious health
      consequences; however, research about its prevalence and correlates in older
      women is limited. We analyzed data from 75,256 women participating in the Women's
      Health Initiative Observational Study, a longitudinal study of postmenopausal
      women's health. Measures used in the study were collected at baseline and/or the
      third year of follow-up between 1993 and 2002. The majority of participants (83%)
      in this study were dissatisfied with their bodies because they perceived
      themselves as heavier than their ideal. Overall, the multiple and significant
      correlates of body image dissatisfaction explained 36.2% of the variance in the
      body image dissatisfaction score, with body mass index (BMI) and change in BMI
      being the two most important contributors to explaining the variance. The results
      of this study suggest future research should focus on the utility of
      interventions to reduce dissatisfaction with body image in postmenopausal women
      that target either maintenance of a lower BMI through diet and exercise, and/or
      body acceptance. Further, future research should aim to identify factors in
      addition to body size that drive body image dissatisfaction. 

PMID- 26219697
TI  - Maximizing the Therapeutic Potential of HSP90 Inhibitors.
AB  - HSP90 is required for maintaining the stability and activity of a diverse group
      of client proteins, including protein kinases, transcription factors, and steroid
      hormone receptors involved in cell signaling, proliferation, survival,
      oncogenesis, and cancer progression. Inhibition of HSP90 alters the HSP90-client
      protein complex, leading to reduced activity, misfolding, ubiquitination, and,
      ultimately, proteasomal degradation of client proteins. HSP90 inhibitors have
      demonstrated significant antitumor activity in a wide variety of preclinical
      models, with evidence of selectivity for cancer versus normal cells. In the
      clinic, however, the efficacy of this class of therapeutic agents has been
      relatively limited to date, with promising responses mainly observed in breast
      and lung cancer, but no major activity seen in other tumor types. In addition,
      adverse events and some significant toxicities have been documented. Key to
      improving these clinical outcomes is a better understanding of the cellular
      consequences of inhibiting HSP90 that may underlie treatment response or
      resistance. This review considers the recent progress that has been made in the
      study of HSP90 and its inhibitors and highlights new opportunities to maximize
      their therapeutic potential.

PMID- 26219699
TI  - Neonatal abstinence syndrome: a policy perspective.

PMID- 26219700
TI  - Breast milk: the best lovebiotic.

PMID- 26219701
TI  - Reply to 'Breast milk: the best lovebiotic'.

PMID- 26219702
TI  - Parathyroid hormone as a marker for metabolic bone disease of prematurity.

PMID- 26219703
TI  - Increasing incidence and geographic distribution of neonatal abstinence syndrome:
      United States 2009 to 2012.

PMID- 26219704
TI  - Clinical Forms and Animal Models of Hypophosphatasia.
AB  - Hypophosphatasia (HPP) is due to mutations of the tissue non-specific alkaline
      phosphatase (TNAP) gene expressed in the liver, kidney, and bone. TNAP substrates
      include inorganic pyrophosphate cleaved into inorganic phosphate (Pi) in bone,
      pyridoxal-5'-phosphate (PLP), the circulating form of vitamin B6, and
      phosphoethanolamine (PEA). As an autosomal recessive or dominant disease, HPP
      results in a range of clinical forms. Its hallmarks are low alkaline phosphatase
      (AP) and elevated PLP and PEA levels. Perinatal HPP may cause early death with
      respiratory insufficiency and hypomineralization resulting in deformed limbs and
      sometimes near-absence of bones and skull. Infantile HPP is diagnosed before 6
      months of life. Respiratory failure, rib fractures and seizures due to vitamin B6
      deficiency in the brain indicate poor prognosis. Craniosynostosis is frequent.
      Unlike in other forms of rickets, calcium and phosphorus are not decreased,
      resulting in hypercalciuria and nephrocalcinosis. Hypercalcemic crisis may occur.
      Failure to thrive and growth retardation are concerns. In infantile and adult
      forms of HPP, non-traumatic fractures may be the prominent manifestation, with
      otherwise unexplained chronic pain. Progressive myopathy has been described.
      Dental manifestations with early loss of teeth are usual in HPP and in a specific
      form, odontohypophosphatasia. HPP has been studied in knock-out mice models which
      mimic its severe form. Animal models have made a major contribution to the
      development of an original enzyme therapy for human infantile HPP, which is
      however essentially targeted at mineralized tissues. Better knowledge of its
      extraskeletal manifestations, including pain and neurological symptoms, is
      therefore required.

PMID- 26219705
TI  - Molecular Genetics of Hypophosphatasia and Phenotype-Genotype Correlations.
AB  - Hypophosphatasia (HPP) is due to deficient activity of the tissue-nonspecific
      isoenzyme of alkaline phosphatase (TNAP). This enzyme cleaves extracellular
      substrates inorganic pyrophosphates (PPi), pyridoxal-5'-phosphate (PLP),
      phosphoethanolamine (PEA) and nucleotides, and probably other substrates not yet
      identified. During the last 15 years the role of TNAP in mineralization, and to a
      less degree in brain, has been investigated, providing hypotheses and
      explanations for both bone and neuronal HPP phenotypes. ALPL, the gene encoding
      TNAP, is subject to many mutations, mostly missense mutations. A few number of
      mutations are recurrently found and may be quite frequent in particular
      populations. This reflects founder effects. The great variety of mutations
      results in a great number of compound heterozygous genotypes and in highly
      variable clinical expressivity. A good correlation was observed between the
      severity of the disease and in vitro enzymatic activity of the mutant protein
      measured after site-directed mutagenesis. Many missense mutations found in severe
      hypophosphatasia produced a mutant protein that failed to reach the cell membrane
      , was accumulated in the cis-Golgi and was subsequently degraded in the
      proteasome. Missense mutations located in the catalytic site or in the homodimer
      interface were often shown by site-directed mutagenesis to have a dominant
      negative effect. Currently molecular diagnosis of HPP is based on the sequencing
      of the coding sequence of ALPL that allows detection of approximately 95 % of
      mutations in severe cases. In addition, other genes, especially genes encoding
      proteins involved in the regulation of extracellular PPi concentration, could
      modify the phenotype (modifier genes).

PMID- 26219706
TI  - Genetically Modified Mice for Studying TNAP Function.
AB  - Genetically modified mice are powerful tools for understanding the functions of
      genes and proteins and often serve as models of human disease. Here, several
      knockout and transgenic mouse lines related to tissue-nonspecific alkaline
      phosphatase (TNAP) are described. Conventional TNAP knockout mice die before
      weaning and show vitamin B6 dependent epilepsy and impaired bone mineralization,
      mimicking infantile hypophosphatasia. Administration of recombinant human TNAP
      rescues the lethal phenotype and improves bone mineralization in the null
      knockout mice, and this enzyme replacement therapy has been successfully applied
      to the treatment of human patients. Transgenic expression of human TNAP also
      rescues the TNAP knockout mice. Studies of the TNAP knockout mice and their
      double knockouts with ectonucleotide pyrophosphatase/phosphodiesterase 1 or
      progressive ankylosis protein revealed that pyridoxal phosphate and inorganic
      pyrophosphate are natural substrates of TNAP. Bone osteopontin from TNAP knockout
      mice is highly phosphorylated, whereas osteopontin from TNAP knockout mice
      expressing human TNAP is de-phosphorylated, similar to that in wild type mice,
      indicating that osteopontin is also a natural substrate of TNAP and that
      phosphorylated osteopontin contributes the impaired bone mineralization in TNAP
      knockout mice. Conditional TNAP knockout mice and TNAP mutants produced by ENU (N
      ethyl-N-nitrosourea) mutagenesis show milder hypophosphatasia and are expected to
      be useful models of adult hypophosphatasia. 

PMID- 26219707
TI  - Tissue-Nonspecific Alkaline Phosphatase in the Developing Brain and in Adult
      Neurogenesis.
AB  - Tissue-nonspecific alkaline phosphatase is expressed both in the developing and
      adult mammalian brain. Expression is particularly strong in the developing
      nervous system and associated with neurogenic activity. It ceases during later
      development but high expression remains in the rodent adult subventricular zone
      of the lateral ventricles, a neurogenic niche generating new neurons for the
      olfactory bulb. Lower activity is maintained in specific brain regions. In spite
      of the wide expression of the enzyme very little is known concerning its
      regulation of expression and physiological function in nervous tissue. This may
      be one of the reasons why the expression of TNAP in the nervous system to date
      has received relatively little attention. The strong and in part transient
      expression of the enzyme in the developing brain implies, however, a significant
      role in the control of neural development. Interestingly, several factors that
      stimulate TNAP expression or activity have a strong impact on neural development.
      The chapter summarizes major findings regarding the cellular distribution of TNAP
      in the developing brain and the neurogenic niches of the adult brain and in vitro
      evidence for a functional role of TNAP in axon growth and progenitor cell
      proliferation and differentiation. Potential mechanisms of TNAP function are
      discussed.

PMID- 26219708
TI  - Rediscovering TNAP in the Brain: A Major Role in Regulating the Function and
      Development of the Cerebral Cortex.
AB  - The presence of alkaline phosphatase (AP) activity in the neural tissue has been
      described decades ago. However, only recent studies clarified the isotype,
      regional distribution and subcellular localization of the AP expressed in the
      cerebral cortex of diverse mammalian species including the human. In the primate
      brain the discovery that the bone AP isotype (TNAP) is expressed provided the
      opportunity of a deeper understanding of the role of this enzyme in neuronal
      functions based on the knowledge acquired by studying the role of the enzyme in
      hypophosphatasia, mostly in bone mineralization. TNAP exhibits widespread
      substrate specificity and, in the brain, it is potentially involved in the
      regulation of molecules which play fundamental roles in signal transmission and
      development. In light of these observations, the localization of TNAP in the
      human cerebral cortex is of high significance when considering that epilepsy is
      often diagnosed in hypophosphatasia. Here we overview our results on the
      identification of TNAP in the primate cerebral cortex: TNAP exhibits a noticeably
      high activity in the synapses and nodes of Ranvier, is specifically present in
      layer 4 of the sensory cortices and additionally in layer 5 of prefrontal,
      temporal and other associational areas in human. Our studies also indicate that
      bone AP activity depends on the level of sensory input and that its developmental
      time-course exhibits characteristic regional differences. The relevance of our
      findings regarding human cortical physiology and brain disorders are discussed. 

PMID- 26219709
TI  - The Retinal TNAP.
AB  - Accumulating evidence from recent literature underline the important roles of
      tissue non specific alkaline phosphatase (TNAP) in diverse functions as well as
      diseases of the nervous system. Exploration of TNAP in well characterized neural
      circuits such as the retina, might significantly advance our understanding
      regarding neural TNAP's roles. This chapter reviews the scarce literature as well
      as our findings on retinal TNAP. We found that retinal TNAP activity was
      preserved and followed diverse patterns throughout vertebrate evolution. We have
      consistently observed TNAP activity (1) in retinal vessels, (2) in photoreceptors
      and (3) in the majority of the studied species in the outer (OPL) and inner
      plexiform layers (IPL), where synaptic transmission occurs. Importantly, in some
      species the IPL exhibits several TNAP positive strata. These strata exactly
      corresponded those seen after quadruple immunohistochemistry with four canonical
      IPL markers (tyrosine hydroxylase, choline acetyltransferase, calretinin, protein
      kinase C alpha). Diabetes results in diminishing retinal TNAP activity before
      changes in canonical markers could be observed in a rat model. The presence of
      TNAP activity at critical sites of neurotransmission suggests its important and
      evolutionary conserved role in vision. In diabetes, the decreased TNAP activity
      indicates neurological alterations adding further evidence for the role of TNAP
      in brain diseases.

PMID- 26219710
TI  - Tissue Non-specific Alkaline Phosphatase (TNAP) in Vessels of the Brain.
AB  - The microvessels of the brain represent around 3-4 % of the brain compartment but
      constitute the most important length (400 miles) and surface of exchange (20
      m(2)) between the blood and the parenchyma of brain. Under influence of
      surrounding tissues, the brain microvessel endothelium expresses a specific
      phenotype that regulates and restricts the entry of compounds and cells from
      blood to brain, and defined the so-called blood-brain barrier (BBB). Evidences
      that alkaline phosphatase (AP) is a characteristic feature of the BBB phenotype
      that allows differentiating capillary endothelial cells from brain to those of
      the periphery have rapidly emerge. Thenceforth, AP has been rapidly used as a
      biomarker of the blood-brain barrier phenotype. In fact, brain capillary
      endothelial cells (BCECs) express exclusively tissue non-specific alkaline
      phosphatase (TNAP). There are several lines of evidence in favour of an important
      role for TNAP in brain function. TNAP is thought to be responsible for the
      control of transport of some compounds across the plasma membrane of the BCECs.
      Here, we report that levamisole-mediated inhibition of TNAP provokes an increase
      of the permeability to Lucifer Yellow of the endothelial monolayer. Moreover, we
      illustrate the disruption of the cytoskeleton organization. Interestingly, all
      observed effects were reversible 24 h after levamisole removal and correlated
      with the return of a full activity of the TNAP. This reversible effect remains to
      be studied in details to evaluate the potentiality of a levamisole treatment to
      enhance the entry of drugs in the brain parenchyma.

PMID- 26219711
TI  - What Can We Learn About the Neural Functions of TNAP from Studies on Other Organs
      and Tissues?
AB  - To-date, the function of tissue-nonspecific alkaline phosphatase (TNAP) has
      largely been defined through studies in patients and mice affected by
      hypophosphatasia (HPP), a rare inborn-error-of-metabolism caused by mutation(s)
      in the TNAP gene (ALPL). The skeletal disease in HPP can be explained by
      alterations in the Pi/PPi ratio, with accumulation in the concentration of the
      mineralization inhibitor PPi as the culprit in preventing propagation of
      mineralization onto the collagenous extracellular matrix in bones and teeth.
      Accumulation of phosphorylated osteopontin increases the severity of HPP, at
      least in mice. Disruption in the metabolism of vitamin B6 leads to intracellular
      deficiency of pyridoxal, and this causes vitamin B6-responsive seizures in
      patients with the severe forms of the disease. Recent findings also implicate
      TNAP in the metabolism of ATP, in the production of adenosine and in the
      dephosphorylation of the bacterial toxin lipopolysaccharide, all molecules known
      to be involved in inflammation. The role of TNAP in establishing the
      ATP/adenosine ratio is important for purinergic signaling, and these mechanisms
      could be significant in determining axonal growth in the brain. Finally, the
      potential involvement of TNAP in dephosphorylating tau protein and its role in
      the pathogenesis of Alzheimer's disease is intriguing.

PMID- 26219712
TI  - TNAP, an Essential Player in Membrane Lipid Rafts of Neuronal Cells.
AB  - The tissue non-specific alkaline phosphatase (TNAP) is a glycosyl
      phosphatidylinositol (GPI) anchored glycoprotein which exists under different
      forms and is expressed in different tissues. As the other members of the ecto
      phosphatase family, TNAP is targeted to membrane lipid rafts. Such micro domains
      enriched in particular lipids, are involved in cell sorting, are in close contact
      with the cellular cytoskeleton and play the role of signaling platform. In
      addition to its location in functional domains, the extracellular orientation of
      TNAP and the fact this glycoprotein can be shed from plasma membranes, contribute
      to its different phosphatase activities by acting as a phosphomonoesterase on
      various soluble substrates (inorganic pyrophosphate -PPi-, pyridoxal phosphate 
      PLP-, phosphoethanolamine -PEA-), as an ectonucleotidase on nucleotide-phosphate
      and presumably as a phosphatase able to dephosphorylate phosphoproteins and
      phospholipids associated to cells or to extra cellular matrix. More and more data
      accumulate on an involvement of the brain TNAP both in physiological and
      pathological situations. This review will summarize what is known and expected
      from the TNAP localization in lipid rafts with a particular emphasis on the role
      of a neuronal microenvironment on its potential function in the central nervous
      system.

PMID- 26219713
TI  - Signal Transduction Pathways of TNAP: Molecular Network Analyses.
AB  - Despite the growing body of evidence pointing on the involvement of tissue non
      specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy
      and Alzheimer's disease, our understanding about the role of TNAP in the
      regulation of neurotransmission is severely limited. The aim of our study was to
      integrate the fragmented knowledge into a comprehensive view regarding neuronal
      functions of TNAP using objective tools. As a model we used the signal
      transduction molecular network of a pyramidal neuron after complementing with
      TNAP related data and performed the analysis using graph theoretic tools. The
      analyses show that TNAP is in the crossroad of numerous pathways and therefore is
      one of the key players of the neuronal signal transduction network. Through many
      of its connections, most notably with molecules of the purinergic system, TNAP
      serves as a controller by funnelling signal flow towards a subset of molecules.
      TNAP also appears as the source of signal to be spread via interactions with
      molecules involved among others in neurodegeneration. Cluster analyses identified
      TNAP as part of the second messenger signalling cascade. However, TNAP also forms
      connections with other functional groups involved in neuronal signal
      transduction. The results indicate the distinct ways of involvement of TNAP in
      multiple neuronal functions and diseases. 

PMID- 26219714
TI  - Vitamin B-6 Metabolism and Interactions with TNAP.
AB  - Two observations stimulated the interest in vitamin B-6 and alkaline phosphatase
      in brain: the marked increase in plasma pyridoxal phosphate and the occurrence of
      pyridoxine responsive seizures in hypophosphatasia. The increase in plasma
      pyridoxal phosphate indicates the importance of tissue non-specific alkaline
      phosphatase (TNAP) in transferring vitamin B-6 into the tissues. Vitamin B-6 is
      involved in the biosynthesis of most of the neurotransmitters. Decreased gamma
      aminobutyrate (GABA) appears to be most directly related to the development of
      seizures in vitamin B-6 deficiency. Cytosolic pyridoxal phosphatase/chronophin
      may interact with vitamin B-6 metabolism and neuronal development and function.
      Ethanolaminephosphate phospholyase interacts with phosphoethanolamine metabolism.
      Extracellular pyridoxal phosphate may interact with purinoceptors and calcium
      channels. In conclusion, TNAP clearly influences extracellular and intracellular
      metabolism of vitamin B-6 in brain, particularly during developmental stages.
      While effects on GABA metabolism appear to be the major contributor to seizures,
      multiple other intra- and extra-cellular metabolic systems may be affected
      directly and/or indirectly by altered vitamin B-6 hydrolysis and uptake resulting
      from variations in alkaline phosphatase activity. 

PMID- 26219715
TI  - Tetramisole and Levamisole Suppress Neuronal Activity Independently from Their
      Inhibitory Action on Tissue Non-specific Alkaline Phosphatase in Mouse Cortex.
AB  - Tissue non-specific alkaline phosphatase (TNAP) may be involved in the synthesis
      of GABA and adenosine, which are the main inhibitory neurotransmitters in cortex.
      We explored this putative TNAP function through electrophysiological recording
      (local field potential ) in slices of mouse somatosensory cortex maintained in
      vitro. We used tetramisole, a well documented TNAP inhibitor, to block TNAP
      activity. We expected that inhibiting TNAP with tetramisole would lead to an
      increase of neuronal response amplitude, owing to a diminished availability of
      GABA and/or adenosine. Instead, we found that tetramisole reduced neuronal
      response amplitude in a dose-dependent manner. Tetramisole also decreased axonal
      conduction velocity. Levamisole had identical effects. Several control
      experiments demonstrated that these actions of tetramisole were independent from
      this compound acting on TNAP. In particular, tetramisole effects were not stereo
      specific and they were not mimicked by another inhibitor of TNAP, MLS-0038949.
      The decrease of axonal conduction velocity and preliminary intracellular data
      suggest that tetramisole blocks voltage-dependent sodium channels. Our results
      imply that levamisole or tetramisole should not be used with the sole purpose of
      inhibiting TNAP in living excitable cells as it will also block all processes
      that are activity-dependent. Our data and a review of the literature indicate
      that tetramisole may have at least four different targets in the nervous system.
      We discuss these results with respect to the neurological side effects that were
      observed when levamisole and tetramisole were used for medical purposes, and that
      may recur nowadays due to the recent use of levamisole and tetramisole as cocaine
      adulterants.

PMID- 26219716
TI  - TNAP and Pain Control.
AB  - Chronic pain is one of the most debilitating and expensive diseases, yet current
      therapies are often insufficient in bringing about long-term relief. Further,
      many treatments for chronic pain also carry significant side effects. The
      molecule adenosine has long been identified as a potent inhibitor of nociceptive
      circuits in the spinal cord; however, the widespread expression of adenosine
      receptors in many organ systems has limited its use as an analgesic. Recently
      several 5' ectonucleotidases, including tissue non-specific alkaline phosphatase
      (TNAP), have been characterized for their ability to generate endogenous
      adenosine in nociceptive circuitry of the dorsal spinal cord. These
      ectonucleotidases have the ability to hydrolyze the endogenous pronociceptive
      nucleotides like adenosine triphosphate (ATP) into the antinociceptive nucleoside
      adenosine. This chapter discusses the role of TNAP and other ectonucleotidases in
      nociceptive circuits, and their potential as future targets of new therapeutics
      to treat chronic pain. 

PMID- 26219717
TI  - Neurological Symptoms of Hypophosphatasia.
AB  - Hypophosphatasia (HPP) is a bone metabolic disorder caused by mutations in the
      liver/bone/kidney alkaline phosphatase gene (ALPL), which encodes tissue
      nonspecific alkaline phosphatase (TNAP). This disease is characterized by
      disrupted bone and tooth mineralization, and reduced serum AP activity. Along
      with bone and tooth symptoms, many neurological symptoms, seizure,
      encephalopathy, intracranial hypertension, mental retardation, deafness, and
      growth hormone deficiency (GHD), are frequently found in HPP patients. Seizure
      occurs in severe HPP types soon after birth, and responds to pyridoxine, but is
      an indicator of lethal prognosis. Encephalopathy rarely presents in severe HPP
      types, but has severe sequelae. Intracranial hypertension complicated in mild HPP
      types develops after the age of 1 year and sometimes need neurosurgical
      intervention. Mental retardation, deafness and GHD are more frequently found in
      Japanese HPP patients. Mental retardation occurs in all HPP types. Deafness in
      perinatal lethal type is both conductive and sensorineural. GHD develops in all
      but perinatal lethal type and the diagnosis tends to delay. The pathogenesis of
      these neural features of HPP might be due to impairment of both vitamin B6
      metabolism and central nervous system development by ALPL mutations.

PMID- 26219718
TI  - Recombinant Enzyme Replacement Therapy in Hypophosphatasia.
AB  - Hypophosphatasia (HPP) is a rare monogenetic and multisystemic disease with
      involvement of different organs, including bone, muscle, kidney, lung,
      gastrointestinal tract and the nervous system. The exact metabolic mechanisms of
      the effects of TNAP deficiency in different tissues are not understood in detail.
      There is no approved specific treatment for HPP; therefore symptomatic treatment
      in order to improve the clinical features is of major interest. Enzyme
      replacement therapy (ERT) is a relatively new type of treatment based on the
      principle of administering a medical treatment replacing a defective or absent
      enzyme. Recently ERT with a bone targeted recombinant human TNAP molecule has
      been reported to be efficient in ten severely affected patients and improved
      survival of life threatening forms. These results are very promising especially
      with regard to the skeletal phenotype but it is unclear whether ERT also has
      beneficial effects for craniosynostosis and in other affected tissues in HPP such
      as brain and kidney. Long-term data are not yet available and further systematic
      clinical trials are needed. It is also necessary to establish therapeutic
      approaches to help patients who are affected by less severe forms of HPP but also
      suffer from a significant reduction in quality of life. Further basic research on
      TNAP function and role in different tissues and on its physiological substrates
      is critical to gain a better insight in the pathogenesis in HPP. This and further
      experiences in new therapeutic strategies may improve the prognosis and quality
      of life of patients with all forms of HPP. 

PMID- 26219719
TI  - Neurogenetic Aspects of Hyperphosphatasia in Mabry Syndrome.
AB  - An autosomal recessive syndrome of hyperphosphatasia (elevated circulating
      alkaline phosphatase (AP), seizures and neurologic deficits) was first described
      by Mabry and colleagues in 1970. Over the ensuing four decades, few cases were
      reported. In 2010, however, new families were identified and the syndromic nature
      of the disorder confirmed. Shortly thereafter, next generation sequencing was
      used to characterize causative defects in the glycosyl phosphatidylinositol (GPI)
      biosynthetic pathway, based partly on our understanding of how AP is anchored by
      GPI to the plasma membrane. Whether the seizures and cognitive defects seen in
      Mabry syndrome patients are attributable in part to the constant
      hyperphosphatasia is not known, as there are more than 250 other proteins
      dependent on GPI for their anchoring to the plasma membrane. However, Mabry
      syndrome may provide a new window on AP function in growth and development.

PMID- 26219720
TI  - The Role of Tissue Non-specific Alkaline Phosphatase (TNAP) in Neurodegenerative
      Diseases: Alzheimer's Disease in the Focus.
AB  - Tissue non-specific alkaline phosphatase (TNAP) is present on neuronal membranes
      and induces neuronal toxicity via tau dephosphorylation; a mechanism which could
      play a role in the neuronal loss seen in Alzheimer's disease (AD). TNAP increases
      in the plasma following brain injury and cerebrovascular disease. In this chapter
      we summarise our previous work which looked at changes in TNAP activity in the
      brain and plasma of AD individuals and discuss whether these changes may be
      reflective of neuronal loss. Our data demonstrate that TNAP activity is
      significantly increased in the brain in both the sporadic and familial forms of
      AD and that TNAP activity is significantly increased in the plasma in AD
      patients. In addition, we describe a significant inverse correlation between
      plasma TNAP activity and cognitive function in AD. Using these data we propose a
      model for TNAP-induced neurodegeneration in AD resulting from tau
      dephosphorylation following secretion of tau from neuronal cells. 

PMID- 26219721
TI  - TNAP Plays a Key Role in Neural Differentiation as well as in Neurodegenerative
      Disorders.
AB  - New evidences have been reported that point to the ecto-enzyme, tissue
      nonspecific alkaline phosphatase (TNAP), as a key element at the origin of two
      opposite phenomena, neuronal differentiation and neuronal degeneration. During
      brain development, TNAP plays an essential role for establishing neuronal
      circuits. The pro-neuritic effect induced by TNAP, which results in axonal length
      increase, is due to its enzymatic hydrolysis of extracellular ATP at the
      surrounding area of the axonal growth cone . In this way, the activation of P2X7
      receptor is prevented and as a consequence there is no inhibition of axonal
      growth. The existence of a close functional interrelation between both purinergic
      elements is finally supported by the fact that both elements may control, in a
      reciprocal way, the expression level of the other. On the opposite stage, recent
      evidences indicate that TNAP plays a key role in spreading the neurotoxicity
      effect induced by extracellular hyperphosphorylated tau protein, the main
      component of intracellular neurofibrillary tangles present in the brain of
      Alzheimer disease patients. TNAP exhibits a broad substrate specificity and in
      addition to nucleotides it is able to dephosphorylate extracellular proteins,
      such as the hyperphosphorylated tau protein once it is released to the
      extracellular medium. Dephosphorylated tau protein behaves as an agonist of
      muscarinic M1 and M3 receptors, provoking a robust and sustained intracellular
      calcium increase that finally triggering neuronal death. Besides, activation of
      muscarinic receptors by dephosphorylated tau increases the expression of TNAP,
      which could explain the increase in TNAP activity and protein levels detected in
      Alzheimer disease. 

PMID- 26219722
TI  - Erratum to: Genomic analysis in the clinic: benefits and challenges for health
      care professionals and patients in Brazil.

PMID- 26219723
TI  - Renal involvement in tuberous sclerosis complex with emphasis on cystic lesions.
AB  - INTRODUCTION: Tuberous sclerosis complex (TSC) involves frequently the kidneys.
      Lesions encompass mainly angiomyolipoma and cysts. The disease can be associated
      with autosomal dominant polycystic kidney disease leading to the contiguous gene
      syndrome (CGS) The objectives of the present study were to review the US
      appearances of the renal involvement in children affected by classical TSC or by
      the CGS and to verify whether it is possible to differentiate between both
      entities. The evolution of the lesions through time was also studied. MATERIALS
      AND METHODS: 55 cases of patients <16 years with STB were reviewed by two
      pediatric radiologists. Clinical data reviewed included age at diagnosis, genetic
      assessment and complications; US data reviewed included renal size, type of
      lesions (angiomyolipoma-AML, or cysts), number and location as well as their
      evolution with time. Complications were also analyzed. RESULTS: 30 patients (56
      %) had at least one kidney lesion (27 classical TSC and 3 CGS). On the basis of
      the US findings, these patients were separated into four groups. Group 1 (9
      patients) displayed microscopic (diffuse) AML; group 2 (3 patients) displayed
      macroscopic AML; group 3 (9 patients) displayed only renal cysts and group 4 (9
      patients) displayed the association of AML and cysts. Increased renal size, the
      large number and size of cystic lesions were suggestive of the CGS. The isolated
      AML were suggestive of classical STB. The average growth of angiomyolipoma was
      low before age of 12 and exceeded 4 mm/year thereafter. CONCLUSION: In children
      with TSC, renal involvement is common. Some US criteria can help to suggest the
      diagnosis of CGS. The growth of angiomyolipoma is slow before 12 years and
      accelerates thereafter. Complications are rare.

PMID- 26219724
TI  - Biomechanical tactics of chiral growth in emergent aquatic macrophytes.
AB  - Through natural selection, many plant organs have evolved optimal morphologies at
      different length scales. However, the biomechanical strategies for different
      plant species to optimize their organ structures remain unclear. Here, we
      investigate several species of aquatic macrophytes living in the same natural
      environment but adopting distinctly different twisting chiral morphologies. To
      reveal the principle of chiral growth in these plants, we performed systematic
      observations and measurements of morphologies, multiscale structures, and
      mechanical properties of their slender emergent stalks or leaves. Theoretical
      modeling of pre-twisted beams in bending and buckling indicates that the
      different growth tactics of the plants can be strongly correlated with their
      biomechanical functions. It is shown that the twisting chirality of aquatic
      macrophytes can significantly improve their survivability against failure under
      both internal and external loads. The theoretical predictions for different
      chiral configurations are in excellent agreement with experimental measurements. 

PMID- 26219725
TI  - Mannose 6-phosphate-independent Lysosomal Sorting of LIMP-2.
AB  - The lysosomal integral membrane protein type 2 (LIMP-2/SCARB2) has been described
      as a mannose 6-phosphate (M6P)-independent trafficking receptor for beta
      glucocerebrosidase (GC). Recently, a putative M6P residue in a crystal structure
      of a recombinantly expressed LIMP-2 ectodomain has been reported. Based on
      surface plasmon resonance and fluorescence lifetime imaging analyses, it was
      suggested that the interaction of soluble LIMP-2 with the cation-independent M6P
      receptor (MPR) results in M6P-dependent targeting of LIMP-2 to lysosomes. As the
      physiological relevance of this observation was not addressed, we investigated
      M6P-dependent delivery of LIMP-2 to lysosomes in murine liver and mouse embryonic
      fibroblasts. We demonstrate that LIMP-2 and GC reach lysosomes independent of the
      M6P pathway. In fibroblasts lacking either MPRs or the M6P-forming N
      acetylglucosamine (GlcNAc)-1-phosphotransferase, LIMP-2 still localizes to
      lysosomes. Immunoblot analyses also revealed comparable LIMP-2 levels within
      lysosomes purified from liver of wild-type (wt) and GlcNAc-1-phosphotransferase
      defective mice. Heterologous expression of the luminal domain of LIMP-2 in wild
      type, LIMP-2-deficient and GlcNAc-1-phosphotransferase-defective cells further
      established that the M6P modification is dispensable for lysosomal sorting of
      LIMP-2. Finally, cathepsin Z, a known GlcNAc-1-phosphotransferase substrate, but
      not LIMP-2, could be precipitated with M6P-specific antibodies. These data prove
      M6P-independent lysosomal sorting of LIMP-2 and subsequently GC in vivo. 

PMID- 26219726
TI  - Symptom Experience Associated With Immunosuppressive Medications in Chinese
      Kidney Transplant Recipients.
AB  - PURPOSE: Kidney transplant recipients require lifelong treatment with
      immunosuppressive medications to avoid graft rejection and graft loss. Symptoms
      experienced may influence recipients' perceived quality of life and medication
      adherence. The purpose of this study was to evaluate the symptom experience
      associated with immunosuppressive medications in adult kidney transplant
      recipients and to explore the association between the symptom experience and
      adherence to immunosuppressive medications. DESIGN: A cross-sectional design was
      used. The study was conducted in a general hospital in China from October 2013 to
      September 2014. A total of 231 recipients with a follow-up of at least 1 year
      after kidney transplantation were included. METHODS: Symptom experience
      associated with immunosuppressive medications was measured by the 13-item Symptom
      Experience of Immunosuppressive-related Side Effects Scale. Self-reported
      adherence to immunosuppressive medications was assessed using the Adherence with
      Immunosuppressive Medication Scale. Ridit analysis was used to rank symptom
      distress items. FINDINGS: A proportion of 60.6% of recipients were male; the time
      after kidney transplantation was arbitrarily divided into a short-term cohort (1
      4 years) and a long-term cohort (4-16 years) according to the median duration of
      follow-up (4 years). High blood pressure, hair loss, and tiredness were the three
      most distressing symptoms over all items of the whole sample. High blood pressure
      was the most distressing symptom for the 1- to 4-year cohort and the 4- to 16
      year cohort. For men high blood pressure was the most distressing symptom,
      whereas for women hair loss was the most distressing symptom. Recipients in the 4
      to 16-year cohort perceived a higher level of symptom distress compared with
      those in the 1- to 4-year cohort, especially in excess hair growth and difficulty
      sleeping. A negative relationship was found between symptom distress and
      adherence to immunosuppressive medications (r = -.541, p = .000). CONCLUSIONS:
      Recipients in the 4- to 16-year cohort perceived a higher level of symptom
      distress compared with those in the 1- to 4-year cohort, especially in excess
      hair growth and difficulty sleeping. No significant difference was found between
      gender groups. Recipients who reported a higher level of symptom distress were
      more likely to be nonadherent. CLINICAL RELEVANCE: Understanding symptom
      experience of immunosuppressive medications is of importance for healthcare
      providers to offer sophisticated education and develop strategies to improve
      quality of life and medication adherence during follow-up post-transplantation.

PMID- 26219727
TI  - Basimglurant for treatment of major depressive disorder: a novel negative
      allosteric modulator of metabotropic glutamate receptor 5.
AB  - INTRODUCTION: Metabotropic glutamate receptor 5 (mGlu5) negative allosteric
      modulators (NAM) such as 2-Methyl-6-(phenylethynyl)pyridine (MPEP) and 3-((2
      Methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) can produce antidepressant-like
      effects; an example being the forced swim test in rodents. It is therefore of
      high interest that a new mGlu5 NAM called basimglurant (RO4917523, RG7090) was
      recently introduced for clinical development in depression. AREAS COVERED: The
      current article reports on the preclinical and clinical work with basimglurant
      which strongly supports its use for treatment of depression. The authors cover
      the pharmacodynamics, pharmacokinetics and safety and tolerability features of
      basimglurant together with its clinical efficacy in a clinical type II trial.
      EXPERT OPINION: The antidepressant activity of basimglurant may be related to a
      preferential reduction of mGlu5 receptor signaling in distinct populations of
      cortical limbic GABA interneurons causing disinhibition of discrete glutamate
      neuronal networks in brain circuits of mood and emotion. Basimglurant's removal
      of mGlu5 receptor induced inhibition of D2 receptor signaling in A2A-D2-mGlu5
      heteroreceptor complexes of ventral striato-pallidal GABA neurons mediating anti
      reward may also play a role. Basimglurant is a highly promising antidepressant
      drug now in clinical development for depression. However, further clinical trials
      are highly warranted.

PMID- 26219728
TI  - Genetic testing for BRCA1 and BRCA2 in the Province of Ontario.
AB  - In 2001, genetic testing for BRCA1 and BRCA2 was introduced in Ontario, for women
      at high-risk of breast or ovarian cancer. To date over 30,000 individuals have
      been tested throughout Ontario. Testing was offered to all Ontario residents who
      were eligible under any of 13 criteria. We report the results of tests conducted
      at Mount Sinai Hospital from 2007 to 2014. A total of 4726 individuals were
      tested, 764 (16.2%) were found to carry a pathogenic variant (mutation). Among
      3684 women and men who underwent testing without a known familial BRCA mutation,
      331 (9.0%) were found to carry a mutation. Among 1042 women and men tested for a
      known family mutation, 433 (41.6%) were positive. There were 603 female mutation
      carriers, of these, 303 were affected with breast or ovarian cancer (50%) and 16
      with another cancer (2.3%). Of 284 unaffected female carriers, 242 (85%) were
      tested for a known family mutation and 42 (15%) were the first person in the
      family to be tested. By placing greater emphasis on recruiting unaffected female
      relatives of known mutation carriers for testing, greater than one-half of newly
      identified carriers will be unaffected. 

PMID- 26219730
TI  - Efficacy of Endeavor zotarolimus-eluting stent implantation for the treatment of
      very late stent thrombosis with late-acquired incomplete stent apposition after
      sirolimus-eluting stent implantation.
AB  - Very late stent thrombosis (VLST) is a serious complication after percutaneous
      coronary intervention. However, the best therapy for VLST with late-acquired
      incomplete stent apposition and incomplete neointimal coverage remains unknown.
      In these cases, neointimal coverage was nearly complete and no late-acquired
      malapposition was detected at 18 months after Endeavor zotarolimus-eluting stent
      (ZES) implantation for the treatment of VLST with late-acquired incomplete stent
      apposition after sirolimus-eluting stent implantation. We presented that Endeavor
      ZES implantation may become an attractive therapeutic strategy for the treatment
      of VLST with late-acquired incomplete stent apposition and incomplete neointimal
      coverage. 

PMID- 26219729
TI  - Incidence and predictors of ischemic stroke during hospitalization for congestive
      heart failure.
AB  - Heart failure (HF) increases the risk of ischemic stroke. Data regarding the
      incidence and predictors of ischemic stroke during hospitalization for HF are
      limited. The study population of this retrospective cohort study consisted of
      patients with congestive HF, consecutively admitted to our center from October
      2010 to April 2014. We excluded patients complicated with acute myocardial
      infarction, infective endocarditis, and takotsubo cardiomyopathy. We also
      excluded those with dialysis or mechanical circulatory support. We investigated
      the incidence of ischemic stroke during hospitalization for HF. Thereafter, we
      divided the patients without oral anticoagulants at admission into two groups:
      patients with ischemic stroke and those without it, and explored the predictors
      of ischemic stroke. A total of 558 patients (287 without atrial fibrillation
      (AF), 271 with AF) were enrolled. The mean age was 76.8 +/- 12.3 years, and 244
      patients (44 %) were female. The mean left-ventricular ejection fraction was 47.4
      %. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with
      AF). During hospitalization (median length 18 days), symptomatic ischemic stroke
      (excluding catheter-related) occurred in 15 patients (2.7 % of the total, 8
      without AF, 7 with AF). Predictors significantly associated with increased risk
      of ischemic stroke in patients without oral anticoagulants were as follows; short
      term increases in blood urea nitrogen after admission (at day 3; odds ratio (per
      1 md/dl): 1.06, 95 % confidence interval (CI) 1.01-1.11, p = 0.02, and at day 7;
      odds ratio: 1.03, 95 % CI 1.00-1.07, p = 0.03, respectively), and previous stroke
      (odds ratio; 3.33, 95 % CI 1.01-11.00, p = 0.04). The incidence of ischemic
      stroke during hospitalization for HF was high, even in patients without AF.
      Previous stroke and short-term increases in blood urea nitrogen was significantly
      associated with the incidence of ischemic stroke. 

PMID- 26219731
TI  - Exploring Value in Congenital Heart Disease: An Evaluation of Inpatient
      Admissions.
AB  - OBJECTIVES: Understanding value provides an important context for improvement.
      However, most health care models fail to measure value. Our objective was to
      categorize inpatient encounters within an academic congenital heart program based
      on clinical outcome and the cost to achieve the outcome (value). We aimed to
      describe clinical and nonclinical features associated with value. DESIGN: We
      defined hospital encounters based on outcome per resource utilized. We performed
      principal component and cluster analysis to classify encounters based on
      mortality, length of stay, hospital cost and revenue into six classes. We used
      nearest shrunken centroid to identify discriminant features associated with the
      cluster-derived classes. These features underwent hierarchical clustering and
      multivariate analysis to identify features associated with each class. STUDY
      SETTING/PATIENTS: We analyzed all patients admitted to an academic congenital
      heart program between September 1, 2009, and December 31, 2012. OUTCOME
      MEASURES/RESULTS: A total of 2658 encounters occurred during the study period.
      Six classes were categorized by value. Low-performing value classes were
      associated with greater institutional reward; however, encounters with higher
      performing value were associated with a loss in profitability. Encounters that
      included insertion of a pediatric ventricular assist device (log OR 2.5 [95% CI,
      1.78 to 3.43]) and acquisition of a hospital-acquired infection (log OR 1.42 [95%
      CI, 0.99 to 1.87]) were risk factors for inferior health care value. CONCLUSIONS:
      Among the patients in our study, institutional reward was not associated with
      value. We describe a framework to target quality improvement and resource
      management efforts that can benefit patients, institutions, and payers alike.

PMID- 26219732
TI  - Face-to-face tracheal intubation in adult patients: a comparison of the
      AirtraqTM, GlidescopeTM and FastrachTM devices.
AB  - PURPOSE: Airway management in emergency settings can be difficult due to limited
      access to the patient. The use of video laryngoscopes along with the FastrachTM
      device improves tracheal intubation; however, the use of such devices in a face
      to-face intubation model has not been evaluated in adult patients. METHODS: After
      obtaining official approval from the Local Research Ethics Committee and written
      informed consent from the patients, 120 patients were enrolled in this
      prospective randomized study. The patients were ASA I and ASA II according to the
      American Society of Anesthesiologists Physical Status Classification System.
      Rocuronium was administered for neuromuscular blockade following standard
      anesthesia monitoring and induction. The patients were divided into three groups
      (40 patients per group) and their tracheas were intubated via a face-to-face
      approach with the AirtraqTM, GlidescopeTM or FastrachTM devices. RESULTS: The
      intubation success rates of the AirtraqTM, GlidescopeTM and FastrachTM devices
      were similar (100, 98 and 90 %; p = 0.07). The insertion time for the AirtraqTM
      [8.5 (6-11) s] was the shortest followed by the GlidescopeTM [11 (7-19) s] and
      the FastrachTM [16.5 (14.3-21.8) s; p < 0.001]. The intubation time for the
      AirtraqTM [14 (10.3-18.8) s] was shorter than the GlidescopeTM [25 (18-45) s],
      and FastrachTM devices [46.5 (40-65) s; p < 0.001]. The GlidescopeTM device
      required a greater number of optimization maneuvers (p = 0.009) and intubation
      attempts than the AirtraqTM (p = 0.004). Esophageal intubation (p = 0.001) and
      mucosal damage were more common in the FastrachTM group (p = 0.03). CONCLUSIONS:
      The AirtraqTM device provided faster insertion and intubation times and enabled
      better Cormack-Lehane grades. Additionally, the AirtraqTM device required the
      minimum number of optimization maneuvers and was associated with fewer
      complications and fewer intubation attempts than the GlidescopeTM and FastrachTM
      devices during face-to-face tracheal intubation.

PMID- 26219733
TI  - Liberal alcohol legislation: does it amplify the effects among Swiss men of
      person-related risk factors on heavy alcohol use?
AB  - AIM: To estimate the statistical interactions between alcohol policy strength and
      the person-related risk factors of sensation-seeking, antisocial personality
      disorder and attention-deficit/hyperactivity disorder related to heavy alcohol
      use. DESIGN: Cross-sectional survey. SETTING: Young Swiss men living within 21
      jurisdictions across Switzerland. PARTICIPANTS: A total of 5701 Swiss men (mean
      age 20 years) participating in the Cohort Study on Substance Use Risk Factors (C
      SURF). MEASUREMENTS: Outcome measures were alcohol use disorder (AUD) as defined
      in the DSM-5 and risky single-occasion drinking (RSOD). Independent variables
      were sensation-seeking, antisocial personality disorder (ASPD), attention
      deficit/hyperactivity disorder (ADHD) and an index of alcohol policy strength.
      FINDINGS: Alcohol policy strength was protective against RSOD [odds ratio (OR) =
      0.91 (0.84-0.99)], while sensation-seeking and ASPD were risk factors for both
      RSOD [OR = 1.90 (1.77-2.04); OR = 1.69 (1.44-1.97)] and AUD [OR = 1.58 (1.47
      1.71); OR = 2.69 (2.30-3.14)] and ADHD was a risk factor for AUD [OR = 1.08 (1.06
      1.10)]. Significant interactions between alcohol policy strength and sensation
      seeking were identified for RSOD [OR = 1.06 (1.01-1.12)] and AUD [OR = 1.06 (1.01
      1.12)], as well as between alcohol policy strength and ASPD for both RSOD [OR =
      1.17 (1.03-1.31)] and AUD [OR = 1.15 (1.02-1.29)]. These interactions indicated
      that the protective effects of alcohol policy strength on RSOD and AUD were lost
      in men with high levels of sensation-seeking or an ASPD. No interactions were
      detected between alcohol policy strength and ADHD. CONCLUSION: Stronger alcohol
      legislation protects against heavy alcohol use in young Swiss men, but this
      protective effect is lost in individuals with high levels of sensation-seeking or
      having an antisocial personality disorder.

PMID- 26219734
TI  - Reproductive biology of the Alaska skate Bathyraja parmifera, with comments on an
      intersexual individual.
AB  - A total of 1357 specimens of Alaska skate Bathyraja parmifera were collected in
      the eastern Bering Sea by fisheries observers and during scientific groundfish
      surveys from 2003 to 2005. Male and female gonads were examined for maturity
      stage and seasonal reproductive timing. Based on seasonal reproductive data,
      including the occurrence of egg cases, ovum size, ovum number, shell-gland width
      and gonado-somatic index, this species appears to reproduce continually
      throughout the year. Potential effects of maternal size upon the size and number
      of mature oocytes were also investigated, with total length having a significant,
      although weak, influence on both. Morphology of a single intersexual individual
      encountered during the collection period is also described.

PMID- 26219735
TI  - Case of pemphigus with immunoglobulin G and A antibodies, binding to both the
      intercellular spaces and basement membrane zone.
AB  - We report a case involving a 62-year-old woman with in vivo-bound immunoglobulin
      (Ig)G and IgA antibodies in both the intercellular space (ICS) and basement
      membrane zone (BMZ). Her clinical and histopathological features were identical
      with those of pemphigus vulgaris, while the immunopathological findings suggested
      IgG/IgA pemphigus. Direct immunofluorescence (IF) showed in vivo-bound IgG and
      IgA antibodies in the ICS and BMZ, whereas indirect IF showed circulating IgG but
      not IgA antibodies in the ICS and BMZ. The anti-ICS IgG bound to desmoglein-3,
      while the anti-BMZ antibodies bound to the epidermal side of 1 mol/L NaCl-split
      skin. To the best of our knowledge, only two similar cases have been reported so
      far. Furthermore, we also examined IgG subclass distribution of the in vivo-bound
      and circulating anti-ICS and BMZ antibodies, and found that IgG1, IgG2 and IgG4
      bound to ICS of the lesional skins, while IgG1 and IgG3 bound to the BMZ. The
      circulating anti-ICS antibodies belonged to IgG1 and IgG4, while the circulating
      anti-BMZ antibodies to IgG1, IgG2 and IgG4. We report a case involving a 62-year
      old woman with in vivo-bound immunoglobulin (Ig)G and IgA antibodies in both the
      intercellular space (ICS) and basement membrane zone (BMZ). Her clinical and
      histopathological features were identical with those of pemphigus vulgaris, while
      the immunopathological findings suggested IgG/IgA pemphigus. Direct
      immunofluorescence (IF) showed in vivo-bound IgG and IgA antibodies in the ICS
      and BMZ, whereas indirect IF showed circulating IgG but not IgA antibodies in the
      ICS and BMZ. The anti-ICS IgG bound to desmoglein-3, while the anti-BMZ
      antibodies bound to the epidermal side of 1 mol/L NaCl-split skin. To the best of
      our knowledge, only two similar cases have been reported so far. Furthermore, we
      also examined IgG subclass distribution of the in vivo-bound and circulating anti
      ICS and BMZ antibodies, and found that IgG1, IgG2 and IgG4 bound to ICS of the
      lesional skins, while IgG1 and IgG3 bound to the BMZ. The circulating anti-ICS
      antibodies belonged to IgG1 and IgG4, while the circulating anti-BMZ antibodies
      to IgG1, IgG2 and IgG4. 

PMID- 26219737
TI  - Photodynamic therapy (PDT) of cancer: from local to systemic treatment.
AB  - Photodynamic therapy (PDT) requires a medical device, a photosensitizing drug and
      adequate use of both to trigger biological mechanisms that can rapidly destroy
      the primary tumour and provide long-lasting protection against metastasis. We
      present a multidisciplinary view of the issues raised by the development of PDT.
      We show how spectroscopy, photophysics, photochemistry and pharmacokinetics of
      photosensitizers determine the mechanism of cell death and clinical protocols.
      Various examples of combinations with chemotherapies and immunotherapies
      illustrate the opportunities to potentiate the outcome of PDT. Particular
      emphasis is given to the mechanisms that can be exploited to establish PDT as a
      systemic treatment of solid tumours and metastatic disease. 

PMID- 26219736
TI  - A roadmap for the genetic analysis of renal aging.
AB  - Several studies show evidence for the genetic basis of renal disease, which
      renders some individuals more prone than others to accelerated renal aging.
      Studying the genetics of renal aging can help us to identify genes involved in
      this process and to unravel the underlying pathways. First, this opinion article
      will give an overview of the phenotypes that can be observed in age-related
      kidney disease. Accurate phenotyping is essential in performing genetic analysis.
      For kidney aging, this could include both functional and structural changes.
      Subsequently, this article reviews the studies that report on candidate genes
      associated with renal aging in humans and mice. Several loci or candidate genes
      have been found associated with kidney disease, but identification of the
      specific genetic variants involved has proven to be difficult. CUBN, UMOD, and
      SHROOM3 were identified by human GWAS as being associated with albuminuria,
      kidney function, and chronic kidney disease (CKD). These are promising examples
      of genes that could be involved in renal aging, and were further mechanistically
      evaluated in animal models. Eventually, we will provide approaches for performing
      genetic analysis. We should leverage the power of mouse models, as testing in
      humans is limited. Mouse and other animal models can be used to explain the
      underlying biological mechanisms of genes and loci identified by human GWAS.
      Furthermore, mouse models can be used to identify genetic variants associated
      with age-associated histological changes, of which Far2, Wisp2, and Esrrg are
      examples. A new outbred mouse population with high genetic diversity will
      facilitate the identification of genes associated with renal aging by enabling
      high-resolution genetic mapping while also allowing the control of environmental
      factors, and by enabling access to renal tissues at specific time points for
      histology, proteomics, and gene expression. 

PMID- 26219738
TI  - Radiation Protection of the Child from Diagnostic Imaging.
AB  - In recent years due to the technological advances in imaging techniques, which
      have undoubtedly improved diagnostic accuracy and resulted in improved patient
      care, the utilization of ionizing radiation in diagnostic imaging has
      significantly increased. Computed tomography is the major contributor to the
      radiation burden, but fluoroscopy continues to be a mainstay in paediatric
      radiology. The rise in the use of ionizing radiation is of particular concern
      with regard to the paediatric population, as they are up to 10 times more
      sensitive to the effects of radiation than adults, due to their increased tissue
      radiosensitivity, increased cumulative lifetime radiation dose and longer
      lifetime in which to manifest the effects. This article will review the estimated
      radiation risk to the child from diagnostic imaging and summarise the various
      methods through which both the paediatrician and radiologist can practice the
      ALARA (As Low As Reasonably Achievable) principle, which underpins the safe
      practice of radiology. Emphasis is on the justification for an examination, i.e.
      weighing of benefits versus radiation risk, on the appropriate utilization of
      other, non-ionizing imaging modalities such as ultrasound and magnetic resonance
      imaging, and on optimisation of a clinically indicated examination. It is
      essential that the paediatrician and radiologist work together in this decision
      making process for the mutual benefit of the patient. The appropriate practical
      application of ALARA in the workplace is crucial to the radiation safety of our
      paediatric patients. 

PMID- 26219739
TI  - Interventional Radiology in Paediatrics.
AB  - As in adult practice, there is a growing role for paediatric interventional
      radiology expertise in the management of paediatric pathologies. This review is
      targeted for clinicians who may refer their patients to paediatric interventional
      radiology services, or who are responsible for patients who are undergoing
      paediatric interventional radiology procedures. The article includes a brief
      overview of the indications for intervention, techniques involved and the
      commonest complications. Although some of the procedures described are most
      commonly performed in a tertiary paediatric centre, many are performed in most
      Children's hospitals. 

PMID- 26219740
TI  - Neuroimaging of Non-Accidental Injury.
AB  - Deliberate inflicted trauma to children has irrefutably occurred for centuries
      but the notion of non-accidental injury (NAI) as a distinct clinical entity has
      only relatively recently been described. Awareness and understanding of this
      syndrome of abuse has increased greatly in recent decades, although many
      alternative names have been given to the condition and uncertainty remains as to
      what exactly comprises the syndrome. What is not in question, however, is the
      role of imaging; the radiologist is often at the front line in terms of raising
      the spectre of NAI and in assessing the probability given the objective imaging
      features available. Non-accidental head injury (NAHI) encompasses a broad
      spectrum of manifestations, ranging from trivial superficial injuries to
      potentially fatal severe brain trauma. In this review, we aim to introduce the
      epidemiological, historical and legal aspects of NAI. Focussing specifically on
      NAHI, current biomechanical theories and neuropathological aspects will be
      discussed. Finally, the patterns of injury and prognosticating features with
      respect to the various imaging modalities will be covered, with careful
      consideration given to differential diagnoses and syndrome mimics. 

PMID- 26219741
TI  - Imaging of Chest and Abdominal Trauma in Children.
AB  - Trauma is the commonest cause of death in children over a year old. The injuries
      sustained and management of these children differs to adults, due to differences
      in anatomy and physiology. Careful thought must also be given to exposing
      children to radiation, and CT scans should be performed only in select patients.
      This article reviews these important points and explains the imaging findings in
      chest and abdominal trauma. 

PMID- 26219742
TI  - Current Gastrointestinal Imaging in Children.
AB  - Gastrointestinal (GI) pathologies in children present with overlapping symptoms
      and signs. Radiological imaging is assuming a more prominent role in the
      diagnostic pathway. This article is aimed primarily at paediatricians, helping
      them to understand and thereby better utilise radiological imaging. The strengths
      and weaknesses of the various imaging modalities are outlined in a concise
      manner. Illustrative conditions are discussed with an emphasis on key diagnostic
      features along with several, high quality annotated images. Emerging concepts are
      introduced throughout the article. These are referenced by the latest research to
      give the reader an update of current GI imaging in children. 

PMID- 26219743
TI  - Completely <001> oriented anatase TiO2 nanoarrays: topotactic growth and
      orientation-related efficient photocatalysis.
AB  - A TiO2 film has been facilely grown on a Ti foil via a general and simple acid
      vapor oxidation (AVO) strategy. Based on detailed characterization by using X-ray
      diffraction (XRD), scanning electron microscopy (SEM) and transmission electron
      microscopy (TEM), we found that the TiO2 film was composed of anatase nanoarrays
      highly oriented along their <001> direction, resulting in a large exposed {001}
      top surface on the film. The growth mechanism based on a topotactic
      transformation was proposed according to a careful study of time-dependent
      experimental results. Resulting from the evaluation of photocatalytic performance
      compared with a commercial TiO2 photocatalyst (Degussa P25), the as-prepared
      oriented anatase TiO2 film showed higher efficiency for degradation of atrazine
      and acid orange II (AOII). The performance of photocatalysis is highly relevant
      to the preferential orientation. The efficient photocatalysis could be attributed
      to the highly reactive {001} facets on the anatase nanoarrays with super
      hydrophilicity. 

PMID- 26219744
TI  - The neurobehavioral and molecular phenotype of Angelman Syndrome.
AB  - Angelman Syndrome (AS) is a rare neurodevelopmental disorder associated with
      developmental delay, speech impairment, gait ataxia, and a unique behavioral
      profile. AS is caused by loss of maternal expression of the paternally imprinted
      UBE3A gene. In this study we aim to contribute to understanding of the
      neurobehavioral phenotype of AS with particular focus on the neuropsychiatric
      presentation of the disorder. We also undertake initial exploration of brain
      derived neurotrophic factor (BDNF) plasma levels in AS. Twelve individuals ages 3
      years or older with a confirmed genetic diagnosis of AS underwent detailed
      medical history, phenotypic characterization, and BDNF plasma sampling. The
      results of this study demonstrate that individuals with AS suffer from
      significant developmental delay, impaired adaptive behavior, and sleep
      disruption. Additionally, hyperactivity/impulsivity appears to be the primary
      behavioral domain noted in these individuals. The majority of individuals in this
      project met criteria for autism spectrum disorder on the Autism Diagnostic
      Observation Schedule (ADOS); however, a negative correlation was noted between
      ADOS score and developmental age. BDNF plasma levels in AS individuals were
      significantly elevated compared to neurotypical controls. This is the first
      report of abnormal BDNF levels in AS, and one that necessitates larger future
      studies. The results provide a clue to understanding abnormal neuronal
      development in AS and may help guide future AS research.

PMID- 26219746
TI  - Multi-Stimuli-Responsive Polymeric Materials.
AB  - Stimuli-responsive materials are of immense importance because of their ability
      to undergo alteration of their properties in response to their environment. The
      properties of such materials can be tuned by subtle adjustments in temperature,
      pH, light, and so forth. Among such smart materials, multi-stimuli-responsive
      polymeric materials are of pronounced significance as they offer a wide range of
      applications and their properties can be tuned through several mechanisms. Here,
      we aim to highlight some recent studies showcasing the multi-stimuli-responsive
      character of these polymers, which are still relatively little known compared to
      their single-stimuli-responsive counterpart. 

PMID- 26219745
TI  - Interpersonal traits of psychopathy linked to reduced integrity of the uncinate
      fasciculus.
AB  - Psychopathy is a personality disorder characterized by callous lack of empathy,
      impulsive antisocial behavior, and criminal recidivism. Here, we performed the
      largest diffusion tensor imaging (DTI) study of incarcerated criminal offenders
      to date (N = 147) to determine whether psychopathy severity is linked to the
      microstructural integrity of major white matter tracts in the brain. Consistent
      with the results of previous studies in smaller samples, we found that
      psychopathy was associated with reduced fractional anisotropy in the right
      uncinate fasciculus (UF; the major white matter tract connecting ventral frontal
      and anterior temporal cortices). We found no such association in the left UF or
      in adjacent frontal or temporal white matter tracts. Moreover, the right UF
      finding was specifically related to the interpersonal features of psychopathy
      (glib superficial charm, grandiose sense of self-worth, pathological lying,
      manipulativeness), rather than the affective, antisocial, or lifestyle features.
      These results indicate a neural marker for this key dimension of psychopathic
      symptomatology.

PMID- 26219747
TI  - Poly(p-phenylenediethynylene phosphane): A Phosphorus-Containing Macromolecule
      that Displays Blue Fluorescence Upon Oxidation.
AB  - Despite the challenges associated with their synthesis, hybrid inorganic-organic
      polymers featuring heavier main-group elements spaced by pi-conjugated organic
      functionalities have garnered considerable recent attention due to their chemical
      functionality and novel photophysical properties. We have succeeded in the
      preparation of an unprecedented organophosphorus polymer possessing functional
      phosphane-di-yne moieties in the main chain. Namely, poly(p-phenylenediethynylene
      phosphane) (PPYP) is prepared using a nickel(II)-catalyzed P-C bond-forming
      reaction. The hexyl-substituted PPYPs are solution processible and have been
      thoroughly characterized (molecular weight, Mw, ca. 10(4) Da vs. polystyrene;
      degree of polymerization, DP, ca. 10). Remarkably, although PPYP shows very weak
      emission upon irradiation with UV light, its oxide shows blue "turn-on"
      fluorescence. The present discovery bridges the areas of main-group and polymer
      science and opens the door to a new class of sigma-pi-conjugated macromolecules
      with unique chemical functionality.

PMID- 26219748
TI  - Electronic and magnetic properties of silicon supported organometallic molecular
      wires: a density functional theory (DFT) study.
AB  - The electronic and magnetic properties of transition metal (TM = Sc, Ti, V, Cr
      and Mn) atom incorporated single and double one-dimensional (1D) styrene
      molecular wires confined on the hydrogen-terminated Si(100) surface are explored
      for the first time by means of spin-polarized density functional theory, denoted
      as Si-[TM(styrene)]. It is unveiled that TM atoms bind asymmetrically to the
      adjacent phenyl rings, which leads to novel electronic and magnetic properties in
      stark contrast to the well-studied gas phase TM-benzene molecular wires. Si
      [Mn(styrene)]infinity and Si-[Cr(styrene)]infinity single molecular wires (SMWs)
      are a ferromagnetic semiconductor and half metal, respectively. Creation of H
      atom defects on the silicon surface can introduce an impurity metallic band,
      which leads to novel half-metallic magnetism of a Si-[Mn(styrene)]infinity
      system. Moreover, double molecular wires (DMWs) containing two identical or
      hetero SMWs are theoretically designed. The [Mn(styrene)]infinity
      [Cr(styrene)]infinity DMW exhibits half-metallic magnetism where the spin-up and
      spin-down channels are contributed by two single molecular wires. Finally, we
      demonstrate that introducing a TM-defect may significantly affect the electronic
      structure and magnetic properties of molecular wires. These studies provide new
      insights into the structure and properties of surface supported 1-D sandwiched
      molecular wires and may inspire the future experimental synthesis of substrate
      confined organometallic sandwiched molecular wires. 

PMID- 26219750
TI  - Density functional theory calculations of the hydrazine decomposition mechanism
      on the planar and stepped Cu(111) surfaces.
AB  - We have investigated the adsorption of hydrazine (N2H4) and its reactivity on
      terraces and steps of Cu(111) surfaces by first-principles calculations in order
      to gain insight into the hydrazine decomposition mechanism. We have investigated
      different possibilities for the N-N and N-H bond cleavage for any intermediate
      states by analysing the reaction and barrier energies of each elementary step. We
      have found that hydrazine dehydrogenation via N-H bond scission is neither
      energetically nor kinetically favourable on the flat and stepped surfaces, but
      hydrazine prefers to form NH2via N-N bond decoupling on the Cu(111) with an
      activation energy below 1 eV. The NH2 molecule reacts fairly easily with co
      adsorbed NH2 to form NH3 as well as with N2Hx (x = 1-4) by abstracting hydrogen
      to produce NH3 and N2 molecules on both the flat and stepped surfaces. We also
      found that all intermediates except NNH prefer N-N bond breaking as the most
      likely dissociation pathway, where the amide and imide intermediates produced can
      be hydrogenated to form NH3 in the presence of hydrogen. NNH is the only
      intermediate, which prefers to dissociate via a highly exothermic N-H bond
      breaking process to produce an N2 molecule after overcoming a small barrier
      energy. We also studied the production of H2 by recombination of hydrogen ad
      atoms which, considering the activation energies, is particularly favoured under
      conditions of moderate temperatures. Our results agree well with experiments
      suggesting that N2H4 adsorbs dissociatively on copper above ~300 K leading to N2,
      NH3 and H2. In general, the lower coordination of the steps is found to lead to
      higher reactivity than on the flat Cu(111) surface. Furthermore, the calculations
      show that the influence of step edge atoms is very different for the intra- and
      intermolecular dehydrogenation mechanisms. They also increase the barrier of N-N
      decoupling of all the existing species in the reaction. 

PMID- 26219751
TI  - Stability and bonding of new superalkali phosphide species.
AB  - New superalkali phosphide species with the molecular formulas F2Li3P, F2Li3P2,
      and F4Li6P were investigated. Using the CBS-QB3 composite method to optimize
      geometry and energetic parameters, four monophosphides, two diphosphides, and one
      disuperalkali phosphide were discovered that contain intriguing structural
      features, including hyperlithiation, phosphorus-phosphorus bonds, and planar
      tetracoordinated phosphorus. It is believed that these features lend to the
      stability of these structures and may warrant further experimental investigation
      of these phosphide species to determine if they could play some role in the
      development of novel chemical reactions and/or materials. 

PMID- 26219749
TI  - Initial Benchmarking of the Quality of Medical Care in Childhood-Onset Systemic
      Lupus Erythematosus.
AB  - OBJECTIVE: To assess the quality of medical care in childhood-onset systemic
      lupus erythematosus (SLE) at tertiary pediatric rheumatology centers as measured
      by observance of SLE quality indicators (SLE-QIs). METHODS: International
      consensus has been achieved for childhood-onset SLE-QIs capturing medical care
      provision in 9 domains: diagnostic testing, education of cardiovascular (CV) risk
      and lifestyles, lupus nephritis (LN), medication management, bone health,
      ophthalmologic surveillance, transition, pregnancy, and vaccination. Using
      medical record information, the level of performance of these childhood-onset SLE
      QIs was assessed in childhood-onset SLE populations treated at 4 tertiary
      pediatric rheumatology centers in the US, 2 in Brazil, and 1 center in India.
      RESULTS: A total of 483 childhood-onset SLE patients were assessed. Care for the
      310 US patients differed markedly for childhood-onset SLE-QIs addressing LN, bone
      health, vaccinations, education on CV risk, and transition planning. Performance
      of safety blood testing for medications was high at all centers. Despite often
      similar performance on the childhood-onset SLE-QI, access to kidney biopsies was
      lower in Brazil than in the US. Irrespective of the country of practice, larger
      centers tended to meet the childhood-onset SLE-QIs more often than smaller
      centers. CONCLUSION: The childhood-onset SLE-QIs, evidence-based minimum
      standards of medical care, are not consistently met in the US or some other
      countries outside the US. This has the potential to contribute to suboptimal
      childhood-onset SLE outcomes.

PMID- 26219752
TI  - Gold as an intruder in ZnO nanowires.
AB  - Several techniques for obtaining ZnO nanowires (ZnO NWs) have been reported in
      the literature. In particular, vapour-liquid-solid (VLS) with Au as a catalyst is
      widely used. During this process, Au impurities in the ZnO NWs can be
      incorporated accidentally, and for this reason we named these impurities as
      intruders. It is thought that these intruders may produce interesting alterations
      in the electronic characteristics of nanowires. In the experiment, it is not easy
      to detect either Au atoms in these nanowires, or the modification that intruders
      produce in different electrical, optical and other properties. For this reason,
      in this density functional theory investigation, the effect of Au intruders on
      ZnO NWs is analysed. Au extended (thread) and point defects (atoms replacing Zn
      or O, or Au interstitials) are used to simulate the presence of gold atoms.
      Optimised geometries, band-gaps and density of states indicate that the presence
      of small amounts of Au drastically modifies the electronic states of ZnO NWs. The
      results reported here clearly indicate that small amounts of Au have a strong
      impact on the electronic properties of ZnO NWs, introducing states in the band
      edges that may promote transitions in the visible spectral region. The presence
      of Au as an intruder in ZnO NWs enhances the potential use of this system for
      photonic and photovoltaic applications. 

PMID- 26219753
TI  - Biomechanical comparison of two locking plate constructs under cyclic torsional
      loading in a fracture gap model. Two screws versus three screws per fragment.
AB  - OBJECTIVES: The number of locking screws required per fragment during bridging
      osteosynthesis in the dog has not been determined. The purpose of this study was
      to assess the survival of two constructs, with either two or three screws per
      fragment, under cyclic torsion. METHODS: Ten-hole 3.5 mm stainless steel locking
      compression plates (LCP) were fixed 1 mm away from bone surrogates with a
      fracture gap of 47 mm using two bicortical locking screws (10 constructs) or
      three bicortical locking screws (10 constructs) per fragment, placed at the
      extremities of each LCP. Constructs were tested in cyclic torsion (range: 0 to
      +0.218 rad) until failure. RESULTS: The 3-screws constructs (29.65 +/- 1.89
      N.m/rad) were stiffer than the 2-screws constructs (23.73 +/- 0.87 N.m/rad), and
      therefore, were subjected to a greater torque during cycling (6.05 +/- 1.33 N.m
      and 4.88 +/- 1.14 N.m respectively). The 3-screws constructs sustained a
      significantly greater number of cycles (20,700 +/- 5,735 cycles) than the 2
      screws constructs (15,600 +/- 5,272 cycles). In most constructs, failure was due
      to screw damage at the junction of the shaft and head. The remaining constructs
      failed because of screw head unlocking, sometimes due to incomplete seating of
      the screw head prior to testing. CLINICAL SIGNIFICANCE: Omitting the third
      innermost locking screw during bridging osteosynthesis led to a reduction in
      fatigue life of 25% and construct stiffness by 20%. Fracture of the screws is
      believed to occur sequentially, starting with the innermost screw that initially
      shields the other screws.

PMID- 26219754
TI  - Combination therapy of GLP-1 analogues and insulin: do the benefits outweigh the
      costs?

PMID- 26219755
TI  - High fall incidence and fracture rate in elderly dialysis patients.
AB  - BACKGROUND: Although it is recognised that the dialysis population is ageing
      rapidly, geriatric complications such as falls are poorly appreciated, despite
      the many risk factors for falls in this population. The objective of this study
      was to determine the incidence, complications and risk factors for falls in an
      elderly dialysis population. METHODS: A one-year observational study of chronic
      dialysis patients aged >= 70 years. At baseline, patient characteristics were
      noted and during follow-up the vital parameters and laboratory values were
      recorded. Patients were questioned weekly about falls, fall circumstances and
      consequences by trained nurses. RESULTS: 49 patients were included with a median
      age of 79.3 years (70-89 years). During follow-up 40 fall accidents occurred in
      27 (55%) patients. Falls resulted in fractures in 15% of cases and in hospital
      admissions in 15%. In haemodialysis (HD) patients, the mean systolic blood
      pressure (SBP) before HD was lower in fallers compared with non-fallers (130 vs.
      143 mmHg). Several patients in the lower blood pressure category received
      antihypertensive medication. For every 5 mmHg lower SBP (before HD) the fall risk
      increased by 30% (hazard ratio (HR) 1.30, 95% CI 1.03-1.65, p = 0.03).
      Furthermore, fall risk increased by 22% for every 10 pmol/l rise of parathyroid
      hormone (HR 1.22, 95% CI 1.06-1.39, p = 0.004). CONCLUSIONS: Elderly dialysis
      patients have a high incidence of falls accompanied by a high fracture rate.
      Given the high complication rate, elderly patients at risk of falling should be
      identified and managed. Reduction of blood pressure-lowering medication might be
      a treatment strategy to reduce falls.

PMID- 26219756
TI  - High prevalence of late adverse events in malignant bone tumour survivors
      diagnosed at adult age.
AB  - BACKGROUND: Late treatment-related adverse events are particularly prevalent in
      survivors of childhood bone cancer because of the combination of cytotoxic drugs,
      major surgery and radiotherapy. Existing studies for late toxicity in survivors
      of Ewing's sarcoma (ES) and osteosarcoma (OS) diagnosed at adult age have focused
      on specific sequelae. We investigated a broad spectrum of potential late effects
      in these patients. METHODS: Relapse-free OS and ES patients aged &#8805; 16 at
      diagnosis and treated at the Radboud University Medical Centre (1982-2007) were
      invited for systematic late toxicity screening. This included history taking,
      physical examination, echocardiogram, bone densitometry, audiogram, and serum and
      urine screening for renal toxicity and infertility. Adverse events were graded
      according to the Common Terminology Criteria for Adverse Events version 3.0.
      RESULTS: In 24 survivors (63% male, mean age at screening 45.7 years, mean follow
      up 10.9 years, 70% OS) we found a median of eight adverse events. Frequent
      findings included abnormal gait, osteoporosis, pain, left ventricular systolic
      dysfunction, obesity and nephropathy. The maximum grade of any adverse event was
      mild in four (17%), moderate in 11 (46%), severe in six (25%), and disabling in
      three cases (13%). There was a trend towards more events in patients diagnosed at
      an older age. CONCLUSION: The incidence of late adverse events in this study of
      survivors of bone tumours diagnosed at adult age is higher than in any previously
      published childhood cancer survivorship study. Older patients seem to be
      particularly at risk. Our findings underscore the need for systematic screening
      of late effects in bone cancer survivors of adult age at diagnosis.

PMID- 26219757
TI  - A prospective study of concomitant GLP-1 analogue and insulin use in type 2
      diabetes in clinical practice.
AB  - BACKGROUND: A small number of studies have shown a significant reduction in
      HbA1c, weight and total daily insulin dose when a glucagon-like-peptide-1 (GLP-1)
      analogue was added in type 2 diabetes patients already on insulin treatment.
      Therefore, in a clinical setting, we investigated the effect of adding GLP-1
      analogues in patients with type 2 diabetes already using insulin with respect to
      glycaemic control, body weight and insulin dose. METHODS: In this prospective
      hospital-based study, we included 125 patients suffering from type 2 diabetes,
      treated with insulin and with a body mass index >= 35 kg/m2, who had started on
      GLP-1 analogues (liraglutide/exenatide). HbA1c, body weight, daily insulin dose,
      and side effects were registered at baseline, and after three, six and 12 months.
      RESULTS: HbA1c and weight decreased significantly at all the timepoints (p <=
      0.001 compared with baseline; HbA1c: -5.5 mmol/mol (-0.5%) and weight: -14.3 kg
      after 12 months), with the largest decrease in the first three months. No
      significant correlation was found between weight loss and HbA1c reduction, and
      between duration of diabetes and both weight loss and HbA1c reduction. After six
      and 12 months, the total daily insulin dose decreased significantly (p < 0.001, 
      75.4 IU after 12 months). Moreover, 34% of the patients were able to stop using
      insulin therapy after 12 months. CONCLUSION: By adding a GLP-1 analogue in obese
      patients with type 2 diabetes already on insulin therapy, a significant reduction
      of HbA1c levels and body weight, and a significant reduction in insulin dose or
      complete discontinuation of insulin can be achieved.

PMID- 26219758
TI  - Quantitative ultrasound of the heel as triage test to measure bone mineral
      density compared with dual energy X-ray absorptiometry in men with prostate
      cancer commencing with androgen deprivation therapy.
AB  - OBJECTIVE: Androgen deprivation therapy (ADT) puts patients at an increased risk
      of developing osteoporosis. Assessment of bone mineral density (BMD) is most
      commonly performed by dual energy X-ray absorptiometry (DXA). Alternative ways of
      estimating BMD, such as quantitative ultrasound (QUS) measurement of the heel,
      are explored as DXA is expensive, non-portable and uses ionising radiation. We
      therefore investigated the diagnostic value of QUS as compared with DXA in
      patients commencing ADT. METHODS: In this cross-sectional study of 60 patients
      with prostate cancer who were about to start ADT, BMD was measured with DXA and
      QUS. The fracture risk score, as implemented by the Dutch National Osteoporosis
      Guideline, was also measured. RESULTS: No significant correlations were found
      between the separate DXA T scores and worst DXA T score, and the QUS T scores.
      Correlations between DXA T scores/QUS scores and fracture risk score were also
      non-significant. If QUS had been used as a screening tool, with a threshold of T
      <= -0.5 to perform DXA, then relevant osteopenia/osteoporosis (worst DXA T score
      <= -2.0) would have been missed in 1/18 (5.6%) patients. The negative predictive
      value is 0.95. Using QUS as a screening test prior to DXA and a QUS threshold T
      score <= -0.5 would avoid 21 (35%) DXA scans at the cost of missing one (5.6%)
      case. CONCLUSION: QUS testing cannot replace DXA scans fully as a diagnostic
      test. However, QUS can be incorporated as triage test prior to DXA to reduce the
      need for unnecessary DXA scans and the associated costs.

PMID- 26219759
TI  - Determinants of plasma 25-hydroxyvitamin D levels in healthy adults in the
      Netherlands.
AB  - BACKGROUND: Vitamin D plays a key role in maintaining skeletal health, but is
      also related to various non-skeletal health issues. Several determinants have
      been identified that influence blood plasma levels of 25-hydroxyvitamin D (25(OH)
      D), often in specific patients or elderly populations. This paper aims to
      replicate these findings in a healthy population. METHODS: Plasma levels of
      25(OH)D were measured using tandem mass spectrometry. We examined the cross
      sectional association of sociodemographic, health, lifestyle and sampling
      characteristics with 25(OH)D in a group of 539 adults, who were healthy control
      subjects in the NESDA study in the Netherlands (latitude 52  degrees N). RESULTS:
      Mean 25(OH)D levels were 68.0 (+/- 27.2) nmol/l. Levels under 50 nmol/l occurred
      in 27% of the population; 40% reached levels above 75 nmol/l. Women had higher
      levels than men, and the use of oral contraceptives showed a significant positive
      association among females. Subjects with non-European ancestry had dramatically
      lower 25(OH) D levels. Other factors that were negatively associated were body
      mass index and the renal estimated glomerular filtration rate (eGFR).
      Meteorological data replaced season as a significant determinant. Moderate
      alcohol consumption and sports showed a positive association, while physical
      activity and the hepatic marker gamma-glutamyl transferase did not. Our results
      disconfirm the influence of age in this population of under 65 year olds.
      CONCLUSION: Insufficient 25(OH)D levels were common in a healthy population. The
      set of eight variables that were significant in a multiple regression model (sex,
      ancestry, oral contraceptives, eGFR, BMI, sports, alcohol, sunshine) explained
      29.5% of the variance.

PMID- 26219760
TI  - The diagnostic tangle of pyoderma gangrenosum: a case report and review of the
      literature.
AB  - This report describes a 55-year-old patient with the rare inflammatory dermatosis
      pyoderma gangrenosum. It is an often misdiagnosed condition of unclear origin and
      pathogenesis. There is an association with underlying systemic disorders such as
      inflammatory bowel disease, haematological disorders, rheumatological disease or
      solid malignancies, although this last association is still under investigation.
      The diagnosis can be challenging and treatment depends upon the severity of the
      lesions. The long-term prognosis is unpredictable. 

PMID- 26219761
TI  - Hypocitraturia: a common but not well-known cause of nephrolithiasis.
AB  - Nephrolithiasis is a frequent problem that can cause serious morbidity. When
      associated with an underlying metabolic disorder the recurrence rate is higher.
      Hypocitraturia is estimated to be present in 20-60% of cases. Several secondary
      causes are known. Potassium citrate is the primary treatment. In the case we
      present here we emphasise the need for metabolic screening, focussing on
      hypocitraturia, a less well-known cause of nephrolithiasis. 

PMID- 26219762
TI  - Acute sinusitis and blindness as the first presentation of chronic lymphocytic
      leukaemia.
AB  - Chronic lymphocytic leukaemia (CLL) is the most frequent form of leukaemia among
      adults in the Western world, presenting at a median age of 65 years. The
      diagnosis is usually made incidentally during routine blood examination while the
      disease is still in its early phase. We report a case of blindness of 24 hours
      due to acute sinusitis based on CLL localisation in a patient with undiagnosed
      CLL. Emergency endoscopic sinus surgery and intra- and extra-ocular orbital
      decompression were performed. The sinusitis resolved after surgery and
      intravenous antibiotics. Her vision improved within 24 hours and eventually
      recovered completely after six months. Her CLL remained in an indolent state,
      needing no active treatment. This case illustrates that blindness from a
      lymphoproliferative disorder may be treated with emergency endoscopic sinus
      surgery instead of conventional chemotherapy in order to salvage the vision
      first, even if the vision is lost for more than 24 hours. 

PMID- 26219763
TI  - Peritoneal dialysis-associated peritonitis of zoonotic origin, when minor gets
      major.
AB  - A 62-year-old patient with peritoneal dialysis (PD)-associated peritonitis is
      described. Identical strains of Pasteurella multocida and Streptococcus minor
      were cultured from the dialysate, and from the saliva of her recently adopted
      stray cat. Pasteurella is not often encountered as pathogen in PD-associated
      peritonitis, Streptococcus minor has never been cultured in human infection
      before. We emphasise the importance of hygiene in peritoneal dialysis and the
      need for testing pets when zoonotic pathogens are cultured. 

PMID- 26219764
TI  - Deep vein thrombosis: beware what lies beneath.

PMID- 26219765
TI  - Predictive significance of tissue eosinophilia for nasal polyp recurrence in the
      Chinese population.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a
      challenging clinical entity with its propensity for recurrence. Tissue
      eosinophilia is a hallmark of CRSwNP, and its role in polyp recurrence is a
      subject of much investigation. OBJECTIVE: The aim of this study was to evaluate
      the association between clinical parameters, especially tissue eosinophilia and
      polyp recurrence, and to identify the optimal cutoff value of tissue eosinophilia
      as a predictor for polyp recurrence in Chinese subjects. METHODS: Overall, 387
      patients with CRSwNP were enrolled in this retrospective analysis and
      postoperative follow-up for polyp recurrence was over a period that lasted >24
      months (mean [standard deviation], 34.03 +/- 4.95 months). The baseline
      demographic and clinical features and the preoperative computed tomography were
      compared, and mucosal specimens obtained at endoscopic sinus surgery were
      assessed for inflammatory cells by using histocytologic staining. Predictive
      factors associated with polyp recurrence were analyzed by logistic regression
      analysis, and optimal cutoff points of the predictors were determined by receiver
      operating characteristic curves and the Youden index. RESULTS: A total of 55.3%
      patients (214/387) experienced recurrence. Tissue eosinophilia markedly
      outweighed other parameters and correlated with polyp recurrence. Receiver
      operating characteristic curves indicated that a cutoff value of 27% tissue
      eosinophils predicted recurrence with 96.7% sensitivity and 92.5% specificity
      (area under the curve = 0.969; p < 0.001); and an absolute count of 55
      eosinophils per high power field predicted recurrence with 87.4% sensitivity and
      97.1% specificity (area under the curve = 0.969; p < 0.001). CONCLUSION: A tissue
      eosinophil proportion of >27% of total cells or a tissue eosinophil absolute
      count of >55 eosinophils per high power field may act as a reliable prognostic
      indicator for nasal polyp recurrence within 2 years after surgery.

PMID- 26219767
TI  - Nurses need the details on revalidation--fast.

PMID- 26219766
TI  - Computational studies of acetylcholinesterase complexed with fullerene
      derivatives: a new insight for Alzheimer disease treatment.
AB  - Here, we propose five fullerene (C60) derivatives as new drugs against
      Alzheimer's disease (AD). These compounds were designed to act as new human
      acetylcholinesterase (HssAChE) inhibitors by blocking its fasciculin II (FASII)
      binding site. Docking and molecular dynamic results show that our proposals bind
      to the HssAChE tunnel entrance, forming stable complex, and further binding free
      energy calculations suggest that three of the derivatives proposed here could be
      potent HssAChE inhibitors. We found a region formed by a set of residues (Tyr72,
      Asp74, Trp286, Gln291, Tyr341, and Pro344) which can be further exploited in the
      drug design of new inhibitors of HssAChE based on C60 derivatives. Results
      presented here report for the first time by a new class of molecules that can
      become effective drugs against AD. 

PMID- 26219768
TI  - Nurses' input in procurement ensures safety and saves trust money.

PMID- 26219769
TI  - Patient care may be at risk from fatigued staff on 12-hour shifts.

PMID- 26219770
TI  - NHS could offer staff agency-style job flexibility.

PMID- 26219771
TI  - NICE guidance to school nurses on pupils' weight.

PMID- 26219772
TI  - RCN pledges to campaign against NHS pay-cap declaration by the chancellor.

PMID- 26219773
TI  - Discharge procedures fail to meet the needs of vulnerable patients.

PMID- 26219774
TI  - LGBT employees subjected to workplace abuse.

PMID- 26219775
TI  - All A&E blood tests to include HIV.

PMID- 26219776
TI  - Registrants need simple advice to help them navigate revalidation.

PMID- 26219777
TI  - Five-year cancer plan offers specialist care to all patients.

PMID- 26219778
TI  - Some prison nurses 'lack core values'.

PMID- 26219786
TI  - Osteoarthritis.

PMID- 26219780
TI  - Nurses are urged to prepare for revalidation, but clarity is needed.

PMID- 26219788
TI  - Artistic project is a chance to be happy.

PMID- 26219787
TI  - Home comfort helps healing.

PMID- 26219789
TI  - Touchscreen helps to ease cancer worries.

PMID- 26219799
TI  - NHS Blood and Transplant.

PMID- 26219800
TI  - EpSMon.

PMID- 26219802
TI  - #ImInWorkJeremy paints the real picture of NHS workloads.

PMID- 26219804
TI  - Hospitals should not be expected to carry out immigration policies.

PMID- 26219803
TI  - Digital network of writers helps to foster spirit of collaboration.

PMID- 26219805
TI  - Teamwork is vital if patients are going to receive the best care.

PMID- 26219808
TI  - Isn't it time to accentuate the positive in end of life care?

PMID- 26219810
TI  - Disseminating nursing research.
AB  - This article discusses the issues associated with disseminating research findings
      in nursing. It addresses dissemination methods in academic nursing, barriers to
      the use of research in practice and ways to overcome these. The researcher needs
      to be motivated and support from local managers and professional bodies are
      required to complete the dissemination cycle in nursing research. Attention
      should be focused on undertaking research that can be applied to, and is
      meaningful for, nursing practice. This should reduce the hiatus between academic
      nursing research and effective clinical research. 

PMID- 26219811
TI  - Participant experience of a Care Quality Commission inspection.
AB  - The Care Quality Commission (CQC) is the regulator for health and social care in
      England. It sets and monitors standards of care and has legal powers to take
      action when those standards are not met. The CQC now regulates primary care as
      well as hospital, community and social care, with significant influence on
      nursing practice and the conduct of care. This article explains the role and
      function of the CQC and the circumstances in which its current model was devised.
      It discusses the commission's comprehensive inspection approach, with particular
      reference to mental health settings. The article aims to demystify the inspection
      process and put it into context, drawing on the experiences of a director of
      nursing, an expert by experience and a nursing specialist adviser who
      participated in a comprehensive inspection. 

PMID- 26219812
TI  - Concept mapping: a tool for improving patient care.
AB  - This article reviews the use of concept mapping as a person-centred problem
      solving aid to assessment, risk management, care evaluation and care planning for
      nurses. Concept maps are diagrams that are used to organise, represent and create
      knowledge, and provide a useful framework for critical analysis and problem
      solving. Concept mapping is discussed and demonstrated in relation to improving
      the quality of care for patients and as a tool for clinical leadership and
      teamwork. The benefits of concept mapping for patients' wellbeing and safety,
      staff satisfaction and team learning are evidenced. 

PMID- 26219813
TI  - Breaking bad news.

PMID- 26219814
TI  - The key to success.

PMID- 26219815
TI  - Support in a time of peril.

PMID- 26219817
TI  - Too busy to take time out.

PMID- 26219818
TI  - Learning how to make the right decision fast.

PMID- 26219820
TI  - Phylogenomic evidence for recombination of adenoviruses in wild gorillas.
AB  - Human adenoviruses (HAdVs) of species Human mastadenovirus B (HAdV-B) are
      genetically highly diverse and comprise several pathogenic types. AdVs closely
      related to members of HAdV-B infect African great apes and the evolutionary
      origin of HAdV-B has recently been determined in ancient gorillas. Genetic
      evidence for intra- and inter-species recombination has been obtained for AdVs of
      humans and captive great apes, but evidence from wild great apes is lacking. In
      this study, potential HAdV-B members of wild Eastern gorillas were analysed for
      evidence of recombination. One near-complete genome was amplified from primary
      sample material and sequenced, and from another six individuals genome fragments
      were obtained. In phylogenomic analysis, their penton base, pVII-pVI, hexon and
      fiber genes were compared with those of all publicly available HAdV-B full-genome
      sequences of humans and captive great apes. Evidence for intra-species
      recombination between different HAdV-B members of wild gorillas as well as
      between HAdV-B members of chimpanzees and gorillas was obtained. Since zoonotic
      AdVs have been reported to cause respiratory outbreaks in both humans and
      monkeys, and humans in West and Central Africa frequently hunt and butcher
      primates thereby increasing the chance of zoonotic transmission, such HAdV-B
      recombinants might widen the pool of potential human pathogens. 

PMID- 26219819
TI  - Insights into Protein Structure and Dynamics by Ultraviolet and Visible Resonance
      Raman Spectroscopy.
AB  - Raman spectroscopy is a form of vibrational spectroscopy based on inelastic
      scattering of light. In resonance Raman spectroscopy, the wavelength of the
      incident light falls within an absorption band of a chromophore, and this overlap
      of excitation and absorption energy greatly enhances the Raman scattering
      efficiency of the absorbing species. The ability to probe vibrational spectra of
      select chromophores within a complex mixture of molecules makes resonance Raman
      spectroscopy an excellent tool for studies of biomolecules. In this Current
      Topic, we discuss the type of molecular insights obtained from steady-state and
      time-resolved resonance Raman studies of a prototypical photoactive protein,
      rhodopsin. We also review recent efforts in ultraviolet resonance Raman
      investigations of soluble and membrane-associated biomolecules, including
      integral membrane proteins and antimicrobial peptides. These examples illustrate
      that resonance Raman is a sensitive, selective, and practical method for studying
      the structures of biological molecules, and the molecular bonding, geometry, and
      environments of protein cofactors, the backbone, and side chains.

PMID- 26219822
TI  - Androgen receptor- and PIAS1-regulated gene programs in molecular apocrine breast
      cancer cells.
AB  - We have analyzed androgen receptor (AR) chromatin binding sites (ARBs) and
      androgen-regulated transcriptome in estrogen receptor negative molecular apocrine
      breast cancer cells. These analyses revealed that 42% of ARBs and 39% androgen
      regulated transcripts in MDA-MB453 cells have counterparts in VCaP prostate
      cancer cells. Pathway analyses showed a similar enrichment of molecular and
      cellular functions among AR targets in both breast and prostate cancer cells,
      with cellular growth and proliferation being among the most enriched functions.
      Silencing of the coregulator SUMO ligase PIAS1 in MDA-MB453 cells influenced AR
      function in a target-selective fashion. An anti-apoptotic effect of the silencing
      suggests involvement of the PIAS1 in the regulation of cell death and survival
      pathways. In sum, apocrine breast cancer and prostate cancer cells share a core
      AR cistrome and target gene signature linked to cancer cell growth, and PIAS1
      plays a similar coregulatory role for AR in both cancer cell types. 

PMID- 26219821
TI  - Moderate activation of IKK2-NF-kB in unstressed adult mouse liver induces
      cytoprotective genes and lipogenesis without apparent signs of inflammation or
      fibrosis.
AB  - BACKGROUND: The NF-kB signaling, regulated by IKK1-p52/RelB and IKK2-p65, is
      activated by various stresses to protect or damage the liver, in context-specific
      manners. Two previous studies of liver-specific expression of constitutive active
      IKK2 (IKK2ca) showed that strong activation of IKK2-NF-kB in mouse livers caused
      inflammation, insulin resistance, and/or fibrosis. The purpose of this study was
      to understand how moderate activation of IKK2-NF-kB in adult mouse livers alters
      hepatic gene expression and pathophysiology. METHOD: We generated mice with adult
      hepatocyte-specific activation of Ikk2 (Liv-Ikk2ca) using Alb-cre mice and Ikk2ca
      Rosa26 knockin mice in which a moderate expression of Ikk2ca transgene was driven
      by the endogenous Rosa26 promoter. RESULTS: Surprisingly, compared to wild-type
      mice, adult male Liv-Ikk2ca mice had higher hepatic mRNA expression of Ikk2 and
      classical NF-kB targets (e.g. Lcn2 and A20), as well as IKK1, NIK, and RelB, but
      no changes in markers of inflammation or fibrosis. Blood levels of IL-6 and MCP-1
      remained unchanged, and histology analysis showed a lack of injury or
      infiltration of inflammatory cells in livers of Liv-Ikk2ca mice. Moreover, Liv
      Ikk2ca mice had lower mRNA expression of prooxidative enzymes Cyp2e1 and Cyp4a14,
      higher expression of antioxidative enzymes Sod2, Gpx1, and Nqo1, without changes
      in key enzymes for fatty acid oxidation, glucose utilization, or gluconeogenesis.
      In parallel, Liv-Ikk2ca mice and wild-type mice had similar levels of hepatic
      reduced glutathione, endogenous reactive oxygen species, and lipid peroxidation.
      Additionally, Liv-Ikk2ca mice had higher Cyp3a11 without down-regulation of most
      drug processing genes. Regarding nuclear proteins of NF-kB subunits, Liv-Ikk2ca
      mice had moderately higher p65 and p50 but much higher RelB. Results of ChIP-qPCR
      showed that the binding of p50 to multiple NF-kB-target genes was markedly
      increased in Liv-Ikk2ca mice. Additionally, Liv-Ikk2ca mice had moderate increase
      in triglycerides in liver, which was associated with higher lipogenic factors
      Ppargamma, Lxr, Fasn, Scd1, and CD36. CONCLUSION: In summary, moderate activation
      of IKK2-NF-kB in unstressed adult mouse hepatocytes produces a cytoprotective
      gene expression profile and induces lipogenesis without apparent signs of
      inflammation or fibrosis, likely due to strong activation of the anti
      inflammatory IKK1-RelB alternative NF-kB pathway as well as the Lxr.

PMID- 26219823
TI  - Inhibition of adipogenic differentiation of human SGBS preadipocytes by androgen
      regulated microRNA miR-375.
AB  - Late-onset hypogonadism (LOH), defined as a combination of low serum testosterone
      (T) levels in combination with clinical signs and symptoms of androgen deficiency
      in ageing men, is nowadays a well-characterized disease. Testosterone therapy in
      males affected by hypogonadism leads to a significant decrease of fat mass. In
      humans, the exact molecular mechanism of T effects on inhibition of adipogenesis
      is still unknown. We hypothesized that specific microRNAs could be regulated by
      androgens which might cause an inhibition of adipogenic differentiation. To
      confirm this hypothesis, human mesenchymal stem cells and a preadipocyte cell
      line were differentiated into mature adipocytes and in parallel treated with
      testosterone and dihydrotestosterone. The expression level of miR-375 was
      upregulated during adipogenic differentiation and downregulated after androgen
      treatment. Furthermore, we could show that after androgen treatment the decreased
      expression of miR-375 led to increased expression levels of adiponectin receptor
      2 (ADIPOR2) compared to untreated adipocytes. Moreover, inhibition of miR-375
      also mediated a decreased adipogenic differentiation and increased ADIPOR2
      expression levels. In summary, we identified miR-375 as an androgen regulated
      microRNA, which could play an important role for understanding the mechanism of
      the increase in visceral fat mass and the associated insulin resistance caused by
      testosterone deficiency. 

PMID- 26219825
TI  - Medicaid Reimbursement of Mental Health Peer-Run Organizations: Results of a
      National Survey.
AB  - This study sought to understand whether knowledge of the Affordable Care Act
      (ACA) was associated with willingness of mental health peer-run organizations to
      become Medicaid providers. Through the 2012 National Survey of Peer-Run
      Organizations, organizational directors reported their organization's willingness
      to accept Medicaid reimbursement and knowledge about the ACA. Multinomial
      logistic regression was used to model the association between willingness to
      accept Medicaid and the primary predictor of knowledge of the ACA, as well as
      other predictors at the organizational and state levels. Knowledge of the ACA,
      Medicaid expansion, and discussions about healthcare reform were not
      significantly associated with willingness to be a Medicaid provider. Having fewer
      paid staff was associated with not being willing to be a Medicaid provider,
      suggesting that current staffing capacity is related to attitudes about becoming
      a Medicaid provider. Organizations had both ideological and practical concerns
      about Medicaid reimbursement. Concerns about Medicaid reimbursement can
      potentially be addressed through alternative financing mechanisms that should be
      able to meet the needs of peer-run organizations.

PMID- 26219824
TI  - Early-life perturbations in glucocorticoid activity impacts on the structure,
      function and molecular composition of the adult zebrafish (Danio rerio) heart.
AB  - BACKGROUND: Transient early-life perturbations in glucocorticoids (GC) are linked
      with cardiovascular disease risk in later life. Here the impact of early life
      manipulations of GC on adult heart structure, function and gene expression were
      assessed. METHODS AND RESULTS: Zebrafish embryos were incubated in dexamethasone
      (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown
      (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%)
      were maintained until adulthood under normal conditions. Cardiac function, heart
      histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120
      days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts
      with fewer cardiomyocytes, less mature striation pattern, reduced cardiac
      function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo
      adult hearts were smaller with diminished trabecular network pattern, reduced
      expression of vmhc and altered echocardiographic Doppler flow compared to
      controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 +/- 3.1 vs.
      controls 90.2 +/- 1.1 MUm, p < 0.001) with a more mature trabecular network and
      larger cardiomyocytes (1.62 +/- 0.13 cells/MUm vs control 2.18 +/- 0.13
      cells/MUm, p < 0.05) and enhanced cardiac performance compared to controls. Adult
      hearts were larger (1.02 +/- 0.07 MUg/mg vs controls 0.63 +/- 0.06 MUg/mg, p =
      0.0007), had increased vmhc and gr mRNA levels. CONCLUSION: Perturbations in GR
      activity during embryonic development results in short and long-term alterations
      in the heart.

PMID- 26219826
TI  - GSTM1 polymorphism contribute to colorectal cancer in Asian populations: a
      prospective meta-analysis.
AB  - Glutathione S-transferases (GSTs) are enzymes which expressed in many tissues and
      play important roles in neutralization of toxic compounds, and protecting hosts
      against cancer. Among several GSTs, Glutathione S-transferases mu (GSTM) has been
      drawn attention upon the association with the genetic risk for many types of
      cancers. But whether the GSTM1 polymorphisms confer the susceptibility to
      colorectal cancer in Asians has not been well established. We searched the PubMed
      database with GSTM1, polymorphism and colorectal cancer, attempting to identify
      the eligible studies. In total, 33 case-control studies in Asian populations with
      8502 colorectal cancer patients and 13699 controls were included in the current
      meta-analysis. The association between the polymorphism and susceptibility to
      colorectal cancer was evaluated by the odds ratio (OR) and 95% confidence
      intervals (CI). The pooled meta-analysis suggested that GSTM1 null variant was
      correlated to the colorectal cancer risk in Asians. There was a marginal
      heterogeneity among these eligible studies. Nevertheless, cumulative meta
      analysis observed a trend of an obvious association between the GSTM1 null
      genotype and colorectal cancer risk in Asians. In summary, the meta-analysis
      suggested that GSTM1 null polymorphism confer the susceptibility to colorectal
      cancer in Asians, especially in Chinese populations. 

PMID- 26219827
TI  - Myocardial infarction in a patient with hereditary haemorrhagic telangiectasia in
      a remote location.
AB  - CONTEXT: Prompt reperfusion therapy in acute ST-segment elevation myocardial
      infarction (STEMI) improves outcomes and is therefore a key part of the
      management of affected patients. Primary percutaneous coronary intervention
      (PPCI) is preferred over thrombolysis; however, when PPCI is not available within
      an acceptable time frame, thrombolysis should be administered without delay. When
      thrombolysis is contraindicated, this can lead to delays in achieving coronary
      artery reperfusion, and making therapeutic decisions is more challenging. ISSUES:
      A 57-year-old woman with hereditary haemorrhagic telangiectasia (HHT) presented
      with chest pain to local medical services on a Scottish island. Initial
      assessment including 12-lead ECG was performed without delay and led to a
      diagnosis of infero-lateral STEMI. Initial treatment was with antiplatelets,
      nitrate and opiate analgesia. Immediate reperfusion therapy with thrombolysis was
      considered; however, this was contraindicated due to the diagnosis of HHT.
      Following discussion with the regional centre she was treated with heparin and
      urgently transferred to the nearest catheterisation laboratory for PPCI.
      Unfortunately delays in transfer were caused by inclement weather conditions,
      which precluded the use of an air ambulance. The patient reached a cardiac
      catheterisation laboratory by road. A total occlusion of a distal branch of the
      circumflex artery was found to be the culprit lesion and despite wiring and
      ballooning good blood flow was not restored. However, she made a good recovery
      and was discharged home on secondary prevention therapy, which was modified to
      take into account her increased bleeding risk associated with her pre-existing
      HHT. LESSONS LEARNED: In this case, the patient presented early to medical
      services following the onset of symptoms and was immediately assessed, resulting
      in a prompt accurate diagnosis at first medical contact. Despite this, the
      presence of HHT, and the particularities of living in a remote area compounded by
      unfavourable weather conditions, resulted in a delay in definitive treatment that
      would have been available to a similar patient presenting in an urban setting. In
      remote regions where reperfusion therapy for acute STEMI relies more often on
      thrombolysis, an increased awareness of the issues around the contraindication of
      thrombolysis, together with early discussion with a regional cardiology service
      leads to the most efficient way of establishing the best treatment plan for
      individual patients. Despite this, rural patients may remain at a disadvantage.

PMID- 26219828
TI  - Yellow bronchoscopy: a severe case of tracheal and bronchial Jaundice.

PMID- 26219829
TI  - Palladium-Catalyzed Oxidative Cross-Coupling of Conjugated Enynones with
      Organoboronic Acids.
AB  - A palladium-catalyzed oxidative cross-coupling reaction of conjugated enynones
      with organoboronic acids is developed. This reaction provides an efficient
      methodology for the synthesis of functionalized furan derivatives, including 2
      alkenylfurans and furan-substituted 1,3-dienes. Palladium-carbene migratory
      insertion is proposed as the key step in these transformations. Notably, the beta
      hydride elimination process occurs in a stereoselective manner, resulting in the
      formation of double bonds with high (E)-selectivity. 

PMID- 26219830
TI  - Predicting clinical outcomes in patients with HBsAg-positive chronic hepatitis.
AB  - BACKGROUND AND AIMS: The progression of HBsAg-positive chronic hepatitis is
      insidious and unpredictable. Identification of factors leading to either a benign
      or more serious clinical outcome may assist in decision making for antiviral
      therapy. METHODS: From 1989 to 1998, 130 untreated patients with chronic
      hepatitis were enrolled in a prospective study and followed every 3-6 months with
      liver and virologic tests, platelet counts and alpha-fetoprotein (AFP)
      measurements. RESULTS: During a mean follow-up of 107 +/- 86 months, 16 (12.3 %)
      chronic hepatitis patients progressed to cirrhosis (annual rate 1.4 %), and 23
      (17.7 %) reverted to being inactive carriers (annual rate 2.1 %). Compared to
      baseline values, chronic hepatitis patients who progressed to cirrhosis exhibited
      declines in mean platelet counts (225.7-195.2 mm(3), p = 0.008-0.04) during the
      first 4 years of follow-up, while those who reverted to being inactive carriers
      had substantial reductions in mean levels of AST (83.5-27.2 u/l, p < 0.001-0.002)
      and ALT (100.2-29.2 u/l, p < 0.001-0.007). In addition, during spontaneous
      alanine aminotransferase (ALT) flares, patients progressing to cirrhosis had
      concomitant elevations of AFP levels, while patients who became inactive carriers
      maintained normal AFP values during ALT flares (13.45 vs. 4.65 ng/ml, p = 0.001).
      These AFP differences during episodes of ALT flares were similarly observed when
      analyzed in two separate cohorts of cirrhosis and inactive carrier patients.
      CONCLUSION: Patients with chronic hepatitis who progressed to cirrhosis exhibited
      declines in platelet counts and had AFP elevations during ALT flares. To prevent
      progression, serial measurements of these parameters during the chronic hepatitis
      stage will assist in identifying patients requiring antiviral therapy.

PMID- 26219832
TI  - A new expression vector facilitating production and functional analysis of scFv
      antibody fragments selected from Tomlinson I+J phagemid libraries.
AB  - Tomlinson I+J are synthetic phagemid human scFv libraries widely employed to
      obtain specific antibody fragments via a phage display method. The pIT2/HB2151
      expression system proposed by the designers of the libraries has certain
      drawbacks which result in the lack of expression or low expression levels of
      numerous soluble scFvs. At the stage of scFv screening, this may lead to losing
      some excellent antibodies, which can be avoided but requires laborious and
      expensive work. Here we present a new, pET-30-based vector, which is compatible
      with Tomlinson libraries, retains all virtues of pIT2 used as a plasmid and
      eliminates all its flaws. We demonstrate that pET-scFv-T is frequently superior
      to pIT2 in terms of efficient scFv expression. Moreover, an amber suppressor
      bacterial strain, RosettaBlue(DE3)pLysS, transformed with the new vector, pET
      scFv-T, coding for a number of scFvs, produces substantial amounts of functional,
      easy to purify recombinant antibody fragments, regardless of whether their coding
      sequences contain amber codons. Thus, pET-scFv-T/RosettaBlue(DE3)pLysS expression
      system seems to be a perfect tool for screening for the finest soluble scFvs
      selected from Tomlinson I+J, as well as from many other phagemid libraries. 

PMID- 26219831
TI  - Phase change dispersion of plasmonic nano-objects.
AB  - Phase is an inherent and important feature for coherent processes, which,
      unfortunately, has not been completely understood for surface plasmon polariton
      (SPP) and matter interactions. Here we propose a practical approach to extract
      the phase change dispersion during the interaction between free-space light, SPPs
      and nanogroove/slit based on far-field information only. Numerical simulation and
      experimental validation were both presented using nanoslit-groove plasmonic
      interferometers, agreeing well with theoretical near-field analysis. This
      approach is generally feasible to extract the intrinsic phase dispersion of other
      plasmonic nanostructures and can reveal more fundamental features of SPP-matter
      interactions. 

PMID- 26219833
TI  - Counterpoint: Unfair comparisons lead to unwarranted conclusions-Can treatment
      modalities for localized prostate cancer truly be compared without bias?

PMID- 26219834
TI  - Developmental changes in infant brain activity during naturalistic social
      experiences.
AB  - Between 6 and 12 months, typically developing infants undergo a socio-cognitive
      "revolution." The Interactive Specialization (IS) theory of brain development
      predicts that these behavioral changes will be underpinned by developmental
      increases in the power and topographic extent of socially selective cortical
      responses. To test this hypothesis, we used EEG to examine developmental changes
      in cortical selectivity for ecologically valid dynamic social versus non-social
      stimuli in a large cohort of 6- and 12-month-old infants. Consistent with the
      Interactive Specialization model, results showed that differences in EEG Theta
      activity between social and non-social stimuli became more pronounced and
      widespread with age. Differences in EEG activity were most clearly elicited by a
      live naturalistic interaction, suggesting that measuring brain activity in
      ecologically valid contexts is central to mapping social brain development in
      infancy.

PMID- 26219836
TI  - Identification of skin immune cells in non-human primates.
AB  - The skin is a valuable target for vaccine delivery because it contains many
      immune cell populations, notably antigen presenting cells. Skin immune cells have
      been extensively described in mice and humans but not in non-human primates,
      which are pertinent models for immunological research in vaccination. The aim of
      this work was to describe immune cell populations in the epidermis, dermis and
      skin draining lymph nodes in cynomolgus macaques by a single 12-parameter flow
      cytometry protocol. Given that skin cells share several markers, we defined a
      gating strategy to identify accurately immune cells and to limit contamination of
      one immune cell population by another. The epidermis contained CD1a(+)CD1c(-)
      Langerhans cells (LCs), CD3(+) T cells and putative NK cells. The dermis
      contained CD1a(+)CD1c(-) cells, which were similar to LCs, CD1a(+)CD1c(+) dermal
      dendritic cells (DDCs), CD163(high)CD11b(+) resident macrophages, CD3(+) T cells
      and putative NK cells. The skin also contained CD66(+) polymorphonuclear cells in
      some animals. Thus, immune cell populations in the macaque are similar to those
      in humans despite some differences in phenotype. In skin draining lymph nodes, we
      identified migratory LCs, CD1a(+)CD1c(+) DDCs and macrophages. The simultaneous
      identification of these different immune cells with one panel of markers avoids
      the use of large amounts of precious sample and may improve the understanding of
      immune mechanisms in the skin after treatment or vaccination. 

PMID- 26219837
TI  - Psychogeriatric SOS (services-on-screen) - a unique e-health model of
      psychogeriatric rural and remote outreach.

PMID- 26219835
TI  - Estimation of aortic pulse wave transit time in cardiovascular magnetic resonance
      using complex wavelet cross-spectrum analysis.
AB  - BACKGROUND: Aortic pulse wave velocity (PWV), which substantially increases with
      arterial stiffness and aging, is a major predictor of cardiovascular mortality.
      It is commonly estimated using applanation tonometry at carotid and femoral
      arterial sites (cfPWV). More recently, several cardiovascular magnetic resonance
      (CMR) studies have focused on the measurement of aortic arch PWV (archPWV).
      Although the excellent anatomical coverage of CMR offers reliable segmental
      measurement of arterial length, accurate transit time (TT) determination remains
      a challenge. Recently, it has been demonstrated that Fourier-based methods were
      more robust to low temporal resolution than time-based approaches. METHODS: We
      developed a wavelet-based method, which enables temporal localization of signal
      frequencies, to estimate TT from ascending and descending aortic CMR flow curves.
      This method (archPWVWU) combines the robustness of Fourier-based methods to low
      temporal resolution with the possibility to restrict the analysis to the
      reflectionless systolic upslope. We compared this method with Fourier-based
      (archPWVF) and time domain upslope (archPWVTU) methods in relation to linear
      correlations with age, cfPWV and effects of decreasing temporal resolution by
      factors of 2, 3 and 4. We studied 71 healthy subjects (45 +/- 15 years, 29
      females) who underwent CMR velocity acquisitions and cfPWV measurements. RESULTS:
      Comparison with age resulted in the highest correlation for the wavelet-based
      method (archPWVWU:r = 0.84,p < 0.001; archPWVTU:r = 0.74,p < 0.001; archPWVF:r =
      0.63,p < 0.001). Associations with cfPWV resulted in the highest correlations for
      upslope techniques whether based on wavelet (archPWVWU:r = 0.58,p < 0.001) or
      time (archPWVTU:r = 0.58,p < 0.001) approach. Furthermore, while decreasing
      temporal resolution by 4-fold induced only a minor decrease in correlation of
      both archPWVWU (r decreased from 0.84 to 0.80) and archPWVF (r decreased from
      0.63 to 0.51) with age, it induced a major decrease for the archPWVTU age
      relationship (r decreased from 0.74 to 0.38). CONCLUSIONS: By CMR, measurement of
      aortic arch flow TT using systolic upslopes resulted in a better correlation with
      age and cfPWV, as compared to the Fourier-based approach applied on the entire
      cardiac cycle. Furthermore, methods based on harmonic decomposition were less
      affected by low temporal resolution. Since the proposed wavelet approach combines
      these two advantages, it might help to overcome current technical limitations
      related to CMR temporal resolution and evaluation of patients with highly stiff
      arteries.

PMID- 26219838
TI  - Omega-3 fatty acids and adipose tissue function in obesity and metabolic
      syndrome.
AB  - The n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) such as
      eicosapentaenoic (EPA) and docosahexaenoic (DHA) have been reported to improve
      obesity-associated metabolic disorders including chronic inflammation, insulin
      resistance and dyslipidaemia. Growing evidence exits about adipose tissue as a
      target in mediating the beneficial effects of these marine n-3 PUFAs in adverse
      metabolic syndrome manifestations. Therefore, in this manuscript we focus in
      reviewing the current knowledge about effects of marine n-3 PUFAs on adipose
      tissue metabolism and secretory functions. This scope includes n-3 PUFAs actions
      on adipogenesis, lipogenesis and lipolysis as well as on fatty acid oxidation and
      mitochondrial biogenesis. The effects of n-3 PUFAs on adipose tissue glucose
      uptake and insulin signaling are also summarized. Moreover, the roles of
      peroxisome proliferator-activated receptor gamma (PPARgamma) and AMPK activation
      in mediating n-3 PUFAs actions on adipose tissue functions are discussed.
      Finally, the mechanisms underlying the ability of n-3 PUFAs to prevent and/or
      ameliorate adipose tissue inflammation are also revised, focusing on the role of
      n-3 PUFAs-derived specialized proresolving lipid mediators such as resolvins,
      protectins and maresins. 

PMID- 26219839
TI  - Two doctors sentenced in Canary Islands for failing to treat woman with
      hyponatraemia.

PMID- 26219840
TI  - Nurses' knowledge in ethics and their perceptions regarding continuing ethics
      education: a cross-sectional survey among nurses at three referral hospitals in
      Uganda.
AB  - BACKGROUND: High disease burden and scarcity of healthcare resources present
      complex ethical dilemmas for nurses working in developing countries. We assessed
      nurses' knowledge in ethics and their perceptions about Continuous Nurses' Ethics
      Education (CNEE) for in-service nurses. METHODS: Using an anonymous, pre-tested
      self-administered questionnaire, we assessed nurses' knowledge in basic ethics
      concepts at three regional hospitals in Uganda. Adequate knowledge was measured
      by a score >=50% in the knowledge assessment test. Nurses' perceptions on CNEE
      were assessed using a six-point Likert scale. RESULTS: Of 114 nurses, 91% were
      female; with mean age 44.7 (SD 10) years. Half were diploma, 47 (41%)
      certificates, 6 (5%) bachelors' degrees and one masters' level training. Overall,
      18 (16%) scored >=50% in the ethics knowledge test. Nurses with diploma or higher
      level of nursing training were less likely to fail the ethics knowledge than
      certificate-level nurses (OR 0.14, 95% CI: 0.02-0.7). Only 45% had ever attended
      at least one CNEE session and up to 93% agreed that CNEE is required to improve
      nurses' ethics knowledge and practice. CONCLUSIONS: Nurses exhibited low
      knowledge in ethics and positive attitudes towards CNEE. We recommend structured
      CNEE programs to address basic concepts in nursing ethics and their application
      in clinical practice.

PMID- 26219841
TI  - Urban-rural inequality regarding drug prescriptions in primary care facilities -
      a pre-post comparison of the National Essential Medicines Scheme of China.
AB  - OBJECTIVE: To assess the impact of the National Essential Medicines Scheme (NEMS)
      with respect to urban-rural inequalities regarding drug prescriptions in primary
      care facilities. METHODS: A stratified two-stage random sampling strategy was
      used to sample 23,040 prescriptions from 192 primary care facilities from 2009 to
      2010. Difference-in-Difference (DID) analyses were performed to test the
      association between NEMS and urban-rural gaps in prescription patterns. Between
      Group Variance and Theil Index were calculated to measure urban-rural absolute
      and relative disparities in drug prescriptions. RESULTS: The use of the Essential
      Medicines List (EML) achieved a compliance rate of up to 90% in both urban and
      rural facilities. An overall reduction of average prescription cost improved
      economic access to drugs for patients in both areas. However, we observed an
      increased urban-rural disparity in average expenditure per prescription. The rate
      of antibiotics and glucocorticoids prescription remained high, despite a reduced
      disparity between urban and rural facilities. The average incidence of antibiotic
      prescription increased slightly in urban facilities (62 to 63%) and reduced in
      rural facilities (67% to 66%). The urban-rural disparity in the use of parenteral
      administration (injections and infusions) increased, albeit at a high level in
      both areas (44%-52%). CONCLUSION: NEMS interventions are effective in reducing
      the overall average prescription costs. Despite the increased use of the EML,
      indicator performances with respect to rational drug prescribing and use remain
      poor and exceed the WHO/INRUD recommended cutoff values and worldwide benchmarks.
      There is an increased gap between urban and rural areas in the use of parenteral
      administration and expenditure per prescription.

PMID- 26219842
TI  - Reducing alcohol levels in wines through rational and evolutionary engineering of
      Saccharomyces cerevisiae.
AB  - Over the past two decades, the level of ethanol in wine has increased in most
      wine-producing regions, raising a number of issues related to consumer health,
      prevention policies, the effectiveness of the fermentation and wine sensorial
      quality. This review focuses on metabolic challenges and recent achievements in
      the development of Saccharomyces cerevisiae wine strains with reduced ethanol
      yield. Metabolic engineering approaches that have been successfully used to
      optimize endogenous pathways have been gradually replaced in recent years by
      evolutionary engineering strategies, which can generate strains with improved
      phenotypes using new circuits and can be put to immediate commercial use. The
      power of adaptive evolutionary strategies is expected to increase with the rapid
      development of whole-genome sequencing, which, combined with gene expression and
      metabolic flux analysis, enables the identification of the genetic basis of
      improved phenotypes and the transfer of such phenotypes between strains. 

PMID- 26219843
TI  - Presence of Gyriform Air Predicts Unfavorable Outcome in Venous Catheter-Related
      Cerebral Air Embolism.
AB  - BACKGROUND: This study aimed to investigate the clinical predictors of
      unfavorable prognosis in patients with venous catheter-related cerebral air
      embolism. METHODS: An extensive review of English literature was performed to
      obtain reports on cerebral air embolism published between January 1982 and July
      2014 through PubMed, Journal at Ovid, and Web of Science using the Mesh terms and
      keywords "cerebral air embolism" and "cerebral gas embolism." Reports not
      fulfilling the diagnosis of cerebral air embolism and iterant articles were
      excluded. Demographics, clinical manifestations, and imaging findings were
      recorded. The air distribution on initial brain computed tomography (CT) was
      recorded as gyriform air (GF), cavernous sinus bubble, venous sinus bubble, and
      parenchymal and subarachnoid bubble. The enrolled subjects were further divided
      into favorable and unfavorable outcome groups for analyses. RESULTS: Of the 33
      cases enrolled, 31 had documented follow-up outcomes, including 14 with favorable
      and 17 with unfavorable prognoses. Patients with unfavorable outcome had older
      onset age (67.5 +/- 15.8 versus 46.7 +/- 17.0 years, P < .001), higher frequency
      of GF on brain CT (58.8% versus 0%, P < .01), initial consciousness disturbance
      (100% versus 42.9%, P < .001), and hemiparesis (100% versus 42.9%, P < .001), but
      lower frequency of cardiopulmonary symptoms (5.9% versus 64.3%, P < .01). In
      patients with central venous catheter-related cerebral air embolism, the
      retrograde mechanism had a tendency for worse outcomes (43.8% versus 0%, P =
      .023). CONCLUSIONS: In patients with venous catheter-related cerebral air
      embolism, the presence of GF on brain CT imaging, old age, initial conscious
      disturbance, and hemiparesis may predict unfavorable outcomes.

PMID- 26219844
TI  - Visualization of Regional Cerebral Blood Flow Dynamics during Cortical Venous
      Occlusion using Laser Speckle Contrast Imaging in a Rat Model.
AB  - BACKGROUND: Cerebral venous ischemia (CVI) is a rare but potentially significant
      complication of neurosurgical procedures. However, it is still unclear how
      cerebral venous occlusion (VO) affects regional cerebral blood flow (rCBF)
      dynamics. To elucidate its pathophysiology in detail, we examined the real-time
      perfusion dynamics during adjacent vein occlusions using laser speckle contrast
      imaging (LSCI) in a rat 2-vein occlusion model. METHODS: Two cortical veins were
      occluded photochemically using rose Bengal dye in 6 male Wistar rats; rCBF was
      measured in real time with an LSCI before and after VO. Regions of interest were
      defined between the 2 veins (A) and on the opposite side of the first occluded
      vein (B) on semi-quantitative pseudocolor images for off-line analysis.
      Histopathologic evaluation was performed 3 days after the procedure to assess the
      extent of infarction. RESULTS: LSCI revealed a stepwise reduction in CBF, with a
      sudden decrease just after the first vein occlusion (~20%) and a further decrease
      after the second (~30%). Significant differences were observed between rCBF
      dynamics within regions of interest A and B (P = .0004). All rats exhibited
      infarcts in the superficial cerebral cortex histopathologically. CONCLUSIONS:
      This is the first report of LSCI specifically applied to the study of CVI. The
      extensive real-time measurement with high temporal and spatial resolution
      revealed the stepwise reduction in rCBF during sequential VO and the ensuing
      infarcts.

PMID- 26219845
TI  - Effects of MHY908, a New Synthetic PPARalpha/gamma Dual Agonist, on Inflammatory
      Responses and Insulin Resistance in Aged Rats.
AB  - Insulin resistance is common with aging and is associated with the inflammatory
      response in both humans and rodents. A number of peroxisome proliferator
      activated receptor (PPAR) alpha/gamma dual agonists have been tested for their
      abilities to attenuate insulin resistance and type 2 diabetes. However, there is
      no study on the effects of PPARalpha/gamma dual agonists on inflammation and
      insulin resistance during aging. In the present study, we investigated the
      ability of 2-[4-(5-chlorobenzothiazothiazol-2-yl)phenoxy]-2-methyl-propionic acid
      (MHY908), a newly synthesized novel PPARalpha/gamma dual agonist, to suppress the
      inflammatory response and attenuate insulin resistance in aged rats. Twenty-month
      old rats were divided into four groups: ad libitum fed, ad libitum fed
      supplemented with MHY908 (1 mg and 3 mg/kg/day for 4 weeks), and 40% calorie
      restricted. Six-month-old ad libitum fed rats were used as an age control. The
      aged rats supplemented with MHY908 showed reduced serum glucose, triglyceride,
      and insulin levels, as well as reduced liver triglyceride levels. MHY908 brought
      about a reduction in endoplasmic reticulum stress and activation of the c-Jun N
      terminal kinase in the livers of aged rats, which consequently improved insulin
      signaling. In the kidneys of aged rats, the efficacy of MHY908 as a potent anti
      inflammatory agent was shown by its suppression of NF-kappaB activation through
      inhibition of the Akt/IkappaB kinase signaling pathway. Therefore, the major
      finding of this study is that MHY908 acts as a therapeutic agent against age
      related inflammation associated with insulin resistance by activating PPARalpha
      and PPARgamma, thus attenuating endoplasmic reticulum stress.

PMID- 26219846
TI  - The Expression Changes of Inflammasomes in the Aging Rat Kidneys.
AB  - The mechanisms of kidney aging are not yet clear. Studies have shown that
      immunological inflammation is related to kidney aging. Inflammasomes are
      important components of innate immune system in the body. However, the function
      of inflammasomes and their underlying mechanisms in renal aging remain unclear.
      In this study, for the first time, we systematically investigated the role of the
      inflammasomes and the inflammatory responses activated by inflammasomes during
      kidney aging. We found that during kidney aging, the expression levels of the
      molecules associated with the activation of inflammasomes, including toll-like
      receptor-4 and interleukin-1 receptor (IL-1R), were significantly increased;
      their downstream signaling pathway molecule interleukin-1 receptor-associated
      kinase-4 (IRAK4) was markedly activated (Phospho-IRAK4 was obviously increased);
      the nuclear factor-kappaB (NF-kappaB) signaling pathway was activated (the
      activated NF-kappaB pathway molecules Phospho-IKKbeta, Phospho-IkappaBalpha, and
      Phospho-NF-kappaBp65 were significantly elevated); the levels of the inflammasome
      components NOD-like receptor P3 (NLRP3), NLRC4, and pro-caspase-1 were
      prominently upregulated; and the proinflammatory cytokines IL-1beta and IL-18
      were notably increased in the kidneys of 24-month-old (elderly group) rats. These
      results showed that inflammasomes are markedly activated during the renal aging
      process and might induce inflamm-aging by promoting the maturation and secretion
      of the proinflammatory cytokines IL-1beta and IL-18.

PMID- 26219847
TI  - Heritability and Genome-Wide Association Analyses of Human Gait Suggest
      Contribution of Common Variants.
AB  - Human gait is a complex neurological and musculoskeletal function, of which the
      genetic basis remains largely unknown. To determine the influence of common
      genetic variants on gait parameters, we studied 2,946 participants of the
      Rotterdam Study, a population-based cohort of unrelated elderly individuals. We
      assessed 30 gait parameters using an electronic walkway, which yielded seven
      independent gait domains after principal component analysis. Genotypes of
      participants were imputed to the 1,000 Genomes reference panel for generating
      genetic relationship matrices to estimate heritability of gait parameters, and
      for subsequent genome-wide association scans (GWASs) to identify specific
      variants. Gait domains with the highest age- and sex-adjusted heritability were
      Variability (h (2) = 61%), Rhythm (37%), and Tandem (32%). For other gait
      domains, heritability estimates attenuated after adjustment for height and
      weight. Genome-wide association scans identified a variant on 1p22.3 that was
      significantly associated with single support time, a variable from the Rhythm
      domain (rs72953990; N = 2,946; beta [SE] = 0.0069 (0.0012), p = 2.30*10(-8)).
      This variant did not replicate in an independent sample (N = 362; p = .78). In
      conclusion, human gait has highly heritable components that are explained by
      common genetic variation, which are partly attributed to height and weight.
      Collaborative efforts are needed to identify robust single variant associations
      for the heritable parameters.

PMID- 26219848
TI  - Impaired Immune Response in Old Mice Suffering from Obesity and Premature
      Immunosenescence in Adulthood.
AB  - Obesity and aging share an impaired immune system and oxidative and inflammatory
      stress. Therefore, the hypothesis of obesity as a possible model of premature
      immunosenescence has been proposed. In this study, we investigated whether adult
      obese mice, as a consequence of being fed with a fat-rich diet during their
      adolescence, showed premature immunosenescence and if this was aggravated with
      aging. Peritoneal cell suspensions were obtained when ICR/CD1 obese female mice
      were adults (28 weeks) and old (72 weeks), and several functions and antioxidant
      defenses were evaluated. The results showed that the chemotaxis of both
      macrophages and lymphocytes, phagocytosis of macrophages, activity of natural
      killer cells, proliferative response of lymphocytes, interleukin-1beta, tumor
      necrosis factor-alpha, interleukin-6, interleukin-2, and interleukin-10 released
      in leukocyte cultures, as well as antioxidant and oxidant capacity were
      significantly impaired in adult obese mice with respect to adult nonobese mice,
      with values similar to those in chronologically old mice. When these obese
      animals grew older, although having been fed with a standard diet, they showed a
      higher deterioration of their immune functions in comparison with the old control
      group. In conclusion, these results demonstrate that a high fat intake during
      adolescence can produce an obesity state in adult age associated with a premature
      immunosenescence, which is aggravated through aging.

PMID- 26219849
TI  - The Association Between Life-Space and Health Care Utilization in Older Adults
      with Heart Failure.
AB  - BACKGROUND: Life-space is associated with adverse health outcomes in older
      adults, but its role in health care utilization among individuals with heart
      failure is not well understood. We examined the relationship between life-space
      and both emergency department (ED) utilization and hospitalization. METHODS:
      Participants were community-dwelling older adults with a verified diagnosis of
      heart failure who completed a baseline in-home assessment and at least one follow
      up telephone interview. Life-space was measured at baseline and at follow-up
      every 6 months for 8.5 years. Poisson models were used to determine the
      association between life-space, measured at the beginning of each 6-month
      interval, and health care utilization, defined as ED utilization or
      hospitalization in the immediate ensuing 6 months, adjusting for sociodemographic
      and clinical confounders. RESULTS: A total of 147 participants contributed 259
      total health care utilization events involving an ED visit or a hospital
      admission. Multivariate analysis demonstrated an inverse association between life
      space and health care utilization, where a clinically significant 10-point
      difference in life-space was independently associated with a 14% higher rate of
      ED utilization or hospitalization (incidence rate ratio 1.14, 95% CI 1.04-1.26, p
      = .004). CONCLUSIONS: Life-space may be a useful identifier of community-dwelling
      older adults with heart failure at increased risk of ED visits or hospital
      admissions in the ensuing 6 months. Life-space may therefore be a potentially
      important component of intervention programs to reduce health care utilization.

PMID- 26219850
TI  - Association Between Vestibular and Cognitive Function in U.S. Adults: Data From
      the National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Vestibular function declines with age, and emerging evidence suggests
      that vestibular loss is associated with cognitive impairment. Whether vestibular
      dysfunction is associated with age-related cognitive decline is unknown. METHODS:
      We used data from the 1999-2002 National Health and Nutrition Examination Surveys
      to evaluate the influence of vestibular function on cognitive performance in a
      nationally representative sample of U.S. adults aged >=60 years (n = 1,303).
      Vestibular function was measured with the modified Romberg test, and cognitive
      function was measured by the digit symbol substitution (DSS) score test. We also
      developed structural equation models (SEMs) to explore whether vestibular
      dysfunction and associated cognitive impairment mediate the effect of age on
      falls and activities of daily living (ADL) difficulty. RESULTS: Vestibular
      dysfunction was present in 58% of the study population. In multivariate analyses,
      vestibular dysfunction was associated with a 3.4-point lower DSS score (95%
      confidence interval: -5.2, -1.6; p < .0001), equivalent to the effect of 5 years
      of age. Vestibular dysfunction was also associated with a significantly higher
      odds of ADL difficulty (p = .001), and with a 2.6-fold increase in the odds of
      falling (p = .017). SEMs suggested that vestibular function mediates 14.3% of the
      effect of age on cognitive performance. Further SEMs suggested that lower
      cognitive performance mediates the association between vestibular loss and ADL
      difficulty as well as falls. CONCLUSIONS: This study suggests that vestibular
      dysfunction partially mediates the association between age and cognitive
      impairment. Moreover, the cognitive impairment that results from vestibular loss
      may contribute to ADL difficulty and falls in older individuals.

PMID- 26219851
TI  - Coenzyme Q Protects Against Age-Related Alveolar Bone Loss Associated to n-6
      Polyunsaturated Fatty Acid Rich-Diets by Modulating Mitochondrial Mechanisms.
AB  - An age-dependent model of the periodontium was reproduced to evaluate the effect
      of life-long feeding on a low coenzyme Q10 dosage in n-6, n-3 polyunsaturated
      fatty acid or monounsaturated fatty acid-based diets on periodontal tissues of
      young and old rats. Results shown that exacerbated age-related alveolar bone loss
      previously associated to n-6 polyunsaturated fatty acid diet was attenuated by
      coenzyme Q10 Gene expression analysis suggests that involved mechanisms might be
      related to a restored capacity of mitochondria to adapt to aging in gingival
      cells from rats fed on n-6 polyunsaturated fatty acid. In particular, this could
      be due to an age-related increase of the rate of mitochondrial biogenesis and a
      better oxidative and respiratory balance in these animals. From the nutritional
      and clinical point of view, it is noteworthy that supplementation with coenzyme
      Q10 could counteract the negative effects of n-6 polyunsaturated fatty acid on
      alveolar bone loss (a major feature of periodontitis) associated to age.

PMID- 26219852
TI  - Neoadjuvant therapy abolishes the functional benefits of a larger rectal remnant,
      as measured by magnetic resonance imaging after restorative rectal cancer
      surgery.
AB  - BACKGROUND: The combination of advances in surgical technique and neoadjuvant
      therapy for rectal cancer has resulted in more patients undergoing sphincter
      preserving surgery. Unfortunately, numerous patients subsequently experience
      bowel dysfunction, and may suffer from lifelong severe disability with major
      impact on their quality of life. The aim of the present study was to investigate
      whether the risk of severe LARS in patients was associated with the length of
      remnant rectum. METHODS: A total of 125 patients who underwent sphincter
      preserving surgery for rectal cancer were included. Postoperative bowel function
      was assessed using the low anterior resection syndrome (LARS) score a minimum of
      one year following surgery. The length of remnant rectum was measured on
      postoperative MRI of the pelvis and was correlated with the risk of having major
      LARS. RESULTS: Overall, major LARS was observed in 38 per cent of patients. In
      the patients who underwent surgery alone, major LARS was reported by 27 per cent,
      and a larger remnant rectum was associated with a better functional outcome. In
      contrast, 80 per cent of patients who underwent combined preoperative
      chemoradiotherapy and surgery reported having major LARS. No association between
      the length of remnant rectum and the risk of major LARS was observed in patients
      treated with combined neoadjuvant therapy and surgery. CONCLUSION: Both the
      length of remnant rectum and preoperative chemoradiotherapy had a major impact on
      the severity of bowel dysfunction after restorative rectal cancer surgery. No
      functional benefit from an irradiated rectal remnant was observed.

PMID- 26219853
TI  - Primitive sarcoma of the breast: new insight on the proper surgical management.
AB  - BACKGROUND: Primitive sarcoma of the breast is a rare and challenging disease at
      high risk of recurrence and with poor prognosis. There are controversies in the
      diagnosis and management of such solid tumor due to its rarity and heterogeneity.
      This sarcoma is poorly responsive to both chemotherapy and radiotherapy, thus,
      surgery is the first and most important therapeutic approach. However, given the
      rarity of this type tumor it has not be possible to standardize unique guidelines
      for the proper surgical strategy to adopt. Here, we performed a retrospective
      study of new 10 cases of primitive sarcoma of the breast that underwent either
      mastectomy or a more conservative quadrantectomy, in the attempt to better
      standardize correct surgical indications. METHODS: Ten new cases of primitive
      sarcoma of the breast were registered between 2002 and 2012 and constituted the
      study group. They underwent either mastectomy or quadrantectomy and the clinical,
      prognostic and survival characteristics after surgery were analysed. RESULTS:
      Within the group of patients treated with mastectomy, two had metastasis and died
      because of that. Among the five patients treated with quadrantectomy four are
      alive and free of disease after 3 to 5 years follow-up, while the patient with
      sarcoma arising in pregnancy, although is still alive, developed lung metastases
      four years after surgery. CONCLUSIONS: The first and most important therapeutic
      approach to primary sarcomas of the breast is surgical which has the purpose to
      achieve radical tumor excision to prevent local recurrence and skip metastases.
      However, given the rarity of the condition and the consequent small number of
      cases in this, like in similar studies, it is not possible to draw any definitive
      conclusions and further studies with larger numbers are necessary. However it
      would appear that performing a larger procedure such as mastectomy rather than
      performing a more limited one such as a quadrantectomy, has no advantage in terms
      of overall prognosis.

PMID- 26219854
TI  - Spinal cord stimulation for Parkinson's disease: a systematic review.
AB  - Axial symptoms are a late-developing phenomenon in the course of Parkinson's
      disease (PD) and represent a therapeutic challenge given their poor response to
      levodopa therapy and deep brain stimulation. Spinal cord stimulation (SCS) may be
      a new therapeutic approach for the alleviation of levodopa-resistant motor
      symptoms of PD. Our purpose was to systematically review the effectiveness of SCS
      for the treatment of motor symptoms of PD and to evaluate the technical and
      pathophysiological mechanisms that may influence the outcome efficacy of SCS. A
      comprehensive literature search was conducted using electronic databases for the
      period from January 1966 through April 2014. The methodology utilized in this
      work follows a review process derived from evidence-based systematic review and
      meta-analysis of randomized trials described in the PRISMA statement. Reports
      examining SCS for the treatment of PD are limited. Eight studies with a total of
      24 patients were included in this review. The overall motor score of the Unified
      Parkinson's Disease Rating Scale in the on/off-stimulation condition remained
      unchanged in 6 patients and improved in 18 patients after SCS. SCS appears to
      yield positive results for PD symptoms, especially for impairments in gait
      function and postural stability. However, evidence is limited and long-term
      prospective studies will be required to identify the optimal candidates for SCS
      and the best parameters of stimulation and to fully characterize the effects of
      stimulation on motor and nonmotor symptoms of PD. 

PMID- 26219855
TI  - The role of stereotactic radiosurgery in the treatment of intramedullary spinal
      cord neoplasms: a systematic literature review.
AB  - Advances in imaging technology and microsurgical techniques have made
      microsurgical resection the treatment of choice in cases of symptomatic
      intramedullary tumors. The use of stereotactic radiosurgery (SRS) for spinal
      tumors is a recent development, and its application to intramedullary lesions is
      debated. We conducted a literature search through PubMed's MeSH system, compiling
      information regarding intramedullary neoplasms treated by SRS. We compiled
      histology, tumor location and size, treatment modality, radiation dose,
      fractionation, radiation-induced complications, follow-up, and survival. Ten
      papers reporting on 52 patients with 70 tumors were identified. Metastatic
      lesions accounted for 33%, while 67% were primary ones. Tumor location was
      predominantly cervical (53%), followed by thoracic (33%). Mean volume was 0.55
      cm(3) (95% confidence interval (CI), 0.26-0.83). Preferred treatment modality was
      CyberKnife(r) (87%), followed by Novalis(r) (7%) and linear particle accelerator
      (LINAC) (6%). Mean radiation dose was 22.14 Gy (95% CI, 20.75-23.53), with mean
      fractionation of 4 (95% CI, 3-5). Three hemangioblastomas showed cyst
      enlargement. Symptom improvement or stabilization was seen in all but two cases.
      Radionecrotic spots adjacent to treated areas were seen at autopsy in four
      lesions, without clinical manifestations. Overall, clinical and radiological
      outcomes were favorable. Although surgery remains the treatment of choice for
      symptomatic intramedullary lesions, SRS can be a safe and effective option in
      selected cases. While this review suggests the overall safety and efficacy of SRS
      in the management of intramedullary tumors, future studies need randomized,
      homogeneous patient populations followed over a longer period to provide more
      robust evidence in its favor.

PMID- 26219856
TI  - Multiply to conquer: Copy number variations at Ppd-B1 and Vrn-A1 facilitate
      global adaptation in wheat.
AB  - BACKGROUND: Copy number variation was found to be a frequent type of DNA
      polymorphism in the human genome often associated with diseases but its
      importance in crops and the effects on agronomic traits are still largely
      unknown. RESULTS: Here, we employed a large worldwide panel of 1110 winter wheat
      varieties to assess the frequency and the geographic distribution of copy number
      variants at the Photoperiod-B1 (Ppd-B1) and the Vernalization-A1 (Vrn-A1) loci as
      well as their effects on flowering time under field conditions. We identified a
      novel four copy variant of Vrn-A1 and based on the phylogenetic relationships
      among the lines show that the higher copy variants at both loci are likely to
      have arisen independently multiple times. In addition, we found that the
      frequency of the different copy number variants at both loci reflects the
      environmental conditions in the varieties' region of origin and based on multi
      location field trials show that Ppd-B1 copy number has a substantial effect on
      the fine-tuning of flowering time. CONCLUSIONS: In conclusion, our results show
      the importance of copy number variation at Ppd-B1 and Vrn-A1 for the global
      adaptation of wheat making it a key factor for wheat success in a broad range of
      environments and in a wider context substantiate the significant role of copy
      number variation in crops.

PMID- 26219857
TI  - Hox control of Drosophila larval anatomy; The Alary and Thoracic Alary-Related
      Muscles.
AB  - The body plan of arthropods and vertebrates involves the formation of repetitive
      segments, which subsequently diversify to give rise to different body parts along
      the antero-posterior/rostro-caudal body axis. Anatomical variations between body
      segments are crucial for organ function and organismal fitness. Pioneering work
      in Drosophila has established that Hox transcription factors play key roles both
      in endowing initially identical segments with distinct identities and
      organogenesis. The focus of this review is on Alary Muscles (AMs) and the newly
      discovered Thoracic Alary-Related Muscles (TARMs). AMs and TARMs are thin muscles
      which together connect the circulatory system and different midgut regions to the
      exoskeleton, while intertwining with the respiratory tubular network. They were
      hypothesized to represent a new type of muscles with spring-like properties,
      maintaining internal organs in proper anatomical positions during larval
      locomotion. Both the morphology of TARMs relative to AMs, and morphogenesis of
      connected tissues is under Hox control, emphasizing the key role of Hox proteins
      in coordinating the anatomical development of the larva. 

PMID- 26219859
TI  - Exploring naturally occurring ivy nanoparticles as an alternative biomaterial.
AB  - Arabinoglactan protein (AGP)-rich nanoparticles obtained from the sticky exudates
      of Hedera helix (English ivy), have shown promising potential to be used in
      nanomedicine owing to their excellent aqueous solubility, low intrinsic
      viscosity, biocompatibility, and biodegradability. In this study, the
      feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for
      delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to
      develop novel scaffolds for tissue engineering in regenerative medicine are
      evaluated. Via electrostatic and hydrophobic interactions, pH-responsive
      nanoconjugates are formed between the INPs and the doxorubicin (DOX) with an
      entrapment ratio of 77.9+/-3.9%. While the INPs show minimal cytotoxicity, the
      formed INP-DOX conjugates exhibit substantially stronger cytotoxic activity than
      free DOX against multiple cancer cell lines, suggesting a synergistic effect is
      established upon conjugation. The anti-cancer effects of the INP-DOX conjugates
      are further evaluated via in vivo xenograft assays by subcutaneously implanting
      DOX resistant cell line, SW620/Ad-300, into nude mice. The tumor volumes in mice
      treated with the INP-DOX conjugates are significantly less than those of the mice
      treated with free DOX. In addition, the INPs are further exploited as nano
      fillers to develop fibrous scaffolds with collagen, via mimicking the porous
      matrix where the INPs are embedded under natural condition. Enhanced adhesion of
      smooth muscle cells (SMCs) and accelerated proliferation of mouse aortic SMCs are
      observed in this newly constructed scaffold. Overall, the results obtained from
      the present study suggest great potential of the INPs to be used as biocompatible
      nanomaterials in nanomedicine. The AGP-rich INP renders a glycoprotein
      architecture that is amenable for modification according to the functional
      designs, capable of being developed as versatile nanomaterials for extensive
      biomedical applications. STATEMENT OF SIGNIFICANCE: Naturally occurring organic
      nanomaterials have drawn increasing interest for their potential biomedical
      applications in recent years. In this study, a new type of naturally occurring
      nanoparticles obtained from the sticky exudates on the adventitious roots of
      English ivy (H. helix), was explored for its potential biomedical application. In
      particular, the feasibilities of utilizing ivy nanoparticles (INPs) as nano
      carriers for delivering chemotherapeutic drugs in cancer therapy and as nano
      fillers to develop novel scaffolds for tissue engineering in regenerative
      medicine were evaluated both in vitro and in vivo. Overall, the results obtained
      from the present study suggest the great potential of the INPs to be used as
      biocompatible nanomaterials in nanomedicine. This study may open a totally new
      frontier for exploring the biomedical application of naturally occurring
      nanomaterials.

PMID- 26219858
TI  - Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of
      Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver
      disease in the United States, afflicting an estimated 80 to 100 million
      Americans. Nonalcoholic fatty liver disease is a spectrum of liver diseases
      composed of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH).
      Although nonalcoholic fatty liver has a negligible risk of progression, patients
      with NASH often develop cirrhosis or hepatocellular carcinoma. Although liver
      biopsy is required to diagnose NASH, only patients with a high risk of NASH or
      advanced fibrosis require this evaluation. Despite the high prevalence of NAFLD,
      well-defined screening recommendations are currently lacking. In this review,
      suggestions for screening, diagnosis, and initial work-up of NAFLD are given on
      the basis of established guidelines and recent publications. Proposed drug
      treatments of NASH are also discussed, highlighting the study outcomes, as well
      as proposed uses and limitations of these drugs. The literature was searched in
      PubMed using search terms nonalcoholic fatty liver disease and nonalcoholic
      steatohepatitis, with filters of "English language." A date range of January 1,
      2000, to May 1, 2015, was used for the search. The bibliographies of key
      references were also searched manually, and seminal publications before the year
      2000 were included. 

PMID- 26219860
TI  - Copolymers of acrylonitrile with quaternizable thiazole and triazole side-chain
      methacrylates as potent antimicrobial and hemocompatible systems.
AB  - A series of six copolymeric families, P(AN-co-MTAs) with various molar fractions
      of acrylonitrile (fAN) and methacrylates (fMTA) based on 1,3-thiazole and 1,2,3
      triazole pendant groups with several spacers of different length and nature
      (alkyl or succinic), have been synthesized by conventional radical
      polymerization. The molar fraction of acrylonitrile in the copolymers (FAN) was
      determined by CHNS elemental analysis. The copolymers were also characterized by
      ATR-FTIR and molecular weights were determined by size exclusion chromatography
      (SEC). Due to the nucleophilic nature of the azole heterocycles the copolymers
      have been easily modified by N-alkylation reaction with butyl iodide leading to
      polyelectrolytes of diverse amphiphilic balance, P(AN-co-MTAs-BuI). The degree of
      quaternization (DQ) was quantitative in all instances and was determined by (1)H
      NMR spectroscopy. Dynamic light scattering (DLS) measurements were performed in
      order to determine the particle size and the charge density of the systems. The
      antimicrobial activity of the copolymers was studied in terms of minimal
      inhibitory concentration (MIC) against the Gram-positive bacteria Staphylococcus
      aureus, the Gram-negative Pseudomonas aeruginosa and the yeast Candida
      parapsilosis, as well as the cytotoxic activity toward human red blood cells
      (RBCs). These types of amphiphilic copolycations presented high selectivity
      (>300) maintaining moderate to good antimicrobial activity (MIC=4-64 MUg/mL) and
      being non-hemolytic even at high molar fractions of AN in the copolymers compared
      to PMTAs-BuI homopolymers. Moreover, two examples of acrylonitrile-enriched
      copolymers (FAN=0.6) presented an excellent time-killing efficiency against
      microorganisms with 99.9% of killing ranging from 5 to 30 min. Besides, important
      changes in the morphology of the cell envelop of the microorganisms after
      treatment with P(AN-co-MTAs) were observed by Field Emission Scanning Electron
      Microscopy (FE-SEM) compared to untreated samples. These results indicate that
      these quaternized copolymers (QUATs) behave like the corresponding PMTAs-BuI
      homopolymers, being microbiostatic and also highly effective microbiocidal
      agents.

PMID- 26219861
TI  - TGFbeta functionalized starPEG-heparin hydrogels modulate human dermal fibroblast
      growth and differentiation.
AB  - Hydrogels are promising biomaterials that can adapt easily to complex tissue
      entities. Furthermore, chemical modifications enable these hydrogels to become an
      instructive biomaterial to a variety of cell types. Human dermal fibroblasts play
      a pivotal role during wound healing, especially for the synthesis of novel dermal
      tissue replacing the primary fibrin clot. Thus, the control of growth and
      differentiation of dermal fibroblasts is important to modulate wound healing. In
      here, we utilized a versatile starPEG-heparin hydrogel platform that can be
      independently adjusted with respect to mechanical and biochemical properties for
      cultivating human dermal fibroblasts. Cell-based remodeling of the artificial
      matrix was ensured by using matrix metalloprotease (MMP) cleavable crosslinker
      peptides. Attachment and proliferation of fibroblasts on starPEG-heparin
      hydrogels of differing stiffness, density of pro-adhesive RGD peptides and MMP
      cleavable peptide linkers were tested. Binding and release of human TGFbeta1 as
      well as biological effect of the pre-adsorbed growth factor on fibroblast gene
      expression and myofibroblast differentiation were investigated. Hydrogels
      containing RGD peptides supported fibroblast attachment, spreading, proliferation
      matrix deposition and remodeling compared to hydrogels without any modifications.
      Reversibly conjugated TGFbeta1 was demonstrated to be constantly released from
      starPEG-heparin hydrogels for several days and capable of inducing myofibroblast
      differentiation of fibroblasts as determined by induction of collagen type I, ED
      A-Fibronectin expression and incorporation of alpha smooth muscle actin and
      palladin into F-actin stress fibers. Taken together, customized starPEG-heparin
      hydrogels could be of value to promote dermal wound healing by stimulating growth
      and differentiation of human dermal fibroblasts. STATEMENT OF SIGNIFICANCE: The
      increasing number of people of advanced age within the population results in an
      increasing demand for the treatment of non-healing wounds. Hydrogels are
      promising biomaterials for the temporary closure of large tissue defects: They
      can adapt to complex tissue geometry and can be engineered for specific tissue
      needs. We used a starPEG-heparin hydrogel platform that can be independently
      adjusted to mechanical and biochemical characteristics. We investigated how these
      hydrogels can support attachment, proliferation and differentiation of dermal
      fibroblasts. After introducing adhesive peptides these hydrogels support cell
      attachment and proliferation. Moreover, TGFbeta - an essential growth and
      differentiation factor for fibroblasts - can be immobilized reversibly and
      functionally on these hydrogels. Thus, starPEG-heparin hydrogels could be
      developed to bioactive temporary wound dressings.

PMID- 26219863
TI  - Breast cancer survivors' recollection of their illness and therapy seven years
      after enrolment into a randomised controlled clinical trial.
AB  - BACKGROUND: Little is known about the subjective experience of breast cancer
      survivors after primary treatment. However, these experiences are important
      because they shape their communication about their illness in everyday life,
      usage and acceptance of healthcare, and expectations of new generations of
      patients. The present study investigated this topic by combining qualitative and
      quantitative methods. METHODS: Breast cancer survivors in Bavaria, Germany were
      mailed a questionnaire up to seven years after enrolment into a randomised
      controlled clinical trial and start of their therapy. This enquired about their
      worst experiences during the breast cancer episode, positive aspects of the
      illness and any advice they would give to newly diagnosed patients. A category
      system for themes was systematically created and answers were categorised by two
      independent raters. Frequencies of key categories were then quantitatively
      analysed using descriptive statistics. In addition, local treating physicians
      gave their opinion on the response categories chosen by their patients. RESULTS:
      133 (80%) of 166 eligible patients who survived up to seven years returned the
      questionnaire. The most prominent worst experience reported by survivors was
      psychological distress (i.e. anxiety, uncertainty; prevalence 38%) followed by
      chemotherapy (25%), and cancer diagnosis (18%). Positive aspects of the illness
      were reported by 48% with the most frequent including change in life priorities
      (50%) and social support (22%). The most frequent advice survivors gave was
      fighting spirit (i.e. think positive, never give up; prevalence 42%). Overall,
      physicians' estimates of the frequency of these responses corresponded well with
      survivors' answers. CONCLUSIONS: Although physicians' understanding of breast
      cancer patients was good, psychological distress and chemotherapy-related side
      effects were remembered as particularly burdensome by a substantial part of
      survivors. On the one hand, patients' quality of life needs to be assessed
      repeatedly during medical follow-up to identify such specific complaints also
      including specific recommendations to the physician for targeted psychosocial and
      medical support. On the other hand the advices and positive aspects of the
      disease, reported by the survivors, can be used to promote positive ways of
      coping with the illness.

PMID- 26219864
TI  - Flash Joule heating for ductilization of metallic glasses.
AB  - Metallic glasses (MGs) inherit their amorphous structure from the liquid state,
      which predetermines their ability to withstand high loads approaching the
      theoretical limit. However, the absence of slip systems makes them very sensitive
      to the type of loading and extremely brittle in tension. The latter can be
      improved by precipitation of ductile crystals, which suppress a catastrophic
      propagation of shear bands in a glassy matrix. Here we report a novel approach to
      obtain MG-matrix composites with tensile ductility by flash Joule heating applied
      to Cu47.5Zr47.5Al5 (at.%) metallic glass. This homogeneous, volumetric and
      controllable rapid heat treatment allows achieving uniformly distributed
      metastable B2 CuZr crystals in the glassy matrix. It results in a significant
      tensile strain of 6.8+/-0.5%. Moreover, optimized adjustment of the heat
      treatment conditions enables tuning of microstructure to achieve desired
      mechanical properties. 

PMID- 26219865
TI  - Role of IGF-I in follistatin-induced skeletal muscle hypertrophy.
AB  - Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase
      in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway.
      The aim of the present study was to investigate the role of IGF-I and insulin,
      two ligands of the IGF-I receptor, in the follistatin hypertrophic action on
      skeletal muscle. In a first step, we showed that follistatin increases muscle
      mass while being associated with a downregulation of muscle IGF-I expression. In
      addition, follistatin retained its full hypertrophic effect toward muscle in
      hypophysectomized animals despite very low concentrations of circulating and
      muscle IGF-I. Furthermore, follistatin did not increase muscle sensitivity to IGF
      I in stimulating phosphorylation of Akt but, surprisingly, decreased it once
      hypertrophy was present. Taken together, these observations indicate that
      increased muscle IGF-I production or sensitivity does not contribute to the
      muscle hypertrophy caused by follistatin. Unlike low IGF-I, low insulin, as
      obtained by streptozotocin injection, attenuated the hypertrophic action of
      follistatin on skeletal muscle. Moreover, the full anabolic response to
      follistatin was restored in this condition by insulin but also by IGF-I infusion.
      Therefore, follistatin-induced muscle hypertrophy requires the activation of the
      insulin/IGF-I pathway by either insulin or IGF-I. When insulin or IGF-I alone is
      missing, follistatin retains its full anabolic effect, but when both are
      deficient, as in streptozotocin-treated animals, follistatin fails to stimulate
      muscle growth. 

PMID- 26219862
TI  - Biomimetic scaffolds for regeneration of volumetric muscle loss in skeletal
      muscle injuries.
AB  - Skeletal muscle injuries typically result from traumatic incidents such as combat
      injuries where soft-tissue extremity injuries are present in one of four cases.
      Further, about 4.5 million reconstructive surgical procedures are performed
      annually as a result of car accidents, cancer ablation, or cosmetic procedures.
      These combat- and trauma-induced skeletal muscle injuries are characterized by
      volumetric muscle loss (VML), which significantly reduces the functionality of
      the injured muscle. While skeletal muscle has an innate repair mechanism, it is
      unable to compensate for VML injuries because large amounts of tissue including
      connective tissue and basement membrane are removed or destroyed. This results in
      a significant need to develop off-the-shelf biomimetic scaffolds to direct
      skeletal muscle regeneration. Here, the structure and organization of native
      skeletal muscle tissue is described in order to reveal clear design parameters
      that are necessary for scaffolds to mimic in order to successfully regenerate
      muscular tissue. We review the literature with respect to the materials and
      methodologies used to develop scaffolds for skeletal muscle tissue regeneration
      as well as the limitations of these materials. We further discuss the variety of
      cell sources and different injury models to provide some context for the multiple
      approaches used to evaluate these scaffold materials. Recent findings are
      highlighted to address the state of the field and directions are outlined for
      future strategies, both in scaffold design and in the use of different injury
      models to evaluate these materials, for regenerating functional skeletal muscle.
      STATEMENT OF SIGNIFICANCE: Volumetric muscle loss (VML) injuries result from
      traumatic incidents such as those presented from combat missions, where soft
      tissue extremity injuries are represented in one of four cases. These injuries
      remove or destroy large amounts of skeletal muscle including the basement
      membrane and connective tissue, removing the structural, mechanical, and
      biochemical cues that usually direct its repair. This results in a significant
      need to develop off-the-shelf biomimetic scaffolds to direct skeletal muscle
      regeneration. In this review, we examine current strategies for the development
      of scaffold materials designed for skeletal muscle regeneration, highlighting
      advances and limitations associated with these methodologies. Finally, we
      identify future approaches to enhance skeletal muscle regeneration.

PMID- 26219866
TI  - Differential effects of prenatal stress on metabolic programming in diet-induced
      obese and dietary-resistant rats.
AB  - Stress during pregnancy is a known contributing factor for the development of
      obesity in the offspring. Since maternal obesity is on the rise, we wanted to
      identify the effects of prenatal stress in the offspring of diet-induced obese
      (DIO) rats and compare them with the offspring of dietary-resistant (DR) rats. We
      hypothesized that prenatal stress would make both DIO and DR offspring
      susceptible to obesity, but the effect would be more pronounced in DIO rats.
      Pregnant DIO and DR rats were divided into two groups: nonstressed controls
      (control) and prenatal stress (subjected to restraint stress, three times/day
      from days 14 to 21 of gestation). After recording birth weight and weaning
      weight, male offspring were weaned onto a chow diet for 9 wk and shifted to a
      high-fat (HF) diet for 1 wk. At the end of the 10th wk the animals were
      euthanized, and visceral adipose mass, blood glucose, serum insulin, and C
      peptide levels were measured. Prenatal stress resulted in hyperinsulinemia and
      higher C-peptide levels without altering caloric intake, body weight gain, or fat
      mass in the DIO offspring after 1 wk of HF intake, but not in DR offspring. To
      determine the mechanism underlying the hyperinsulinemia, we measured the levels
      of CEACAM1 that are responsible for insulin clearance. CEACAM1 levels in the
      liver were reduced in prenatally stressed DIO offspring after the HF challenge,
      suggesting that preexisting genetic predisposition in combination with prenatal
      stress increases the risk for obesity in adulthood, especially when offspring are
      fed a HF diet. 

PMID- 26219867
TI  - The somatotropic axis and longevity in mice.
AB  - The somatotropic signaling pathway has been implicated in aging and longevity
      studies in mice and other species. The physiology and lifespans of a variety of
      mutant mice, both spontaneous and genetically engineered, have contributed to our
      current understanding of the role of growth hormone and insulin-like growth
      factor I on aging-related processes. Several other mice discovered to live longer
      than their wild-type control counterparts also exhibit differences in growth
      factor levels; however, the complex nature of the phenotypic changes in these
      animals may also impact lifespan. The somatotropic axis impacts several pathways
      that dictate insulin sensitivity, nutrient sensing, mitochondrial function, and
      stress resistance as well as others that are thought to be involved in lifespan
      regulation. 

PMID- 26219868
TI  - Effect of placental restriction and neonatal exendin-4 treatment on postnatal
      growth, adult body composition, and in vivo glucose metabolism in the sheep.
AB  - Intrauterine growth restriction (IUGR) increases the risk of adult type 2
      diabetes (T2D) and obesity. Neonatal exendin-4 treatment can prevent diabetes in
      the IUGR rat, but whether this will be effective in a species where the pancreas
      is more mature at birth is unknown. Therefore, we evaluated the effects of
      neonatal exendin-4 administration after experimental restriction of placental and
      fetal growth on growth and adult metabolic outcomes in sheep. Body composition,
      glucose tolerance, and insulin secretion and sensitivity were assessed in
      singleton-born adult sheep from control (CON; n = 6 females and 4 males) and
      placentally restricted pregnancies (PR; n = 13 females and 7 males) and in sheep
      from PR pregnancies that were treated with exendin-4 as neonates (daily sc
      injections of 1 nmol/kg exendin-4; PR + exendin-4; n = 11 females and 7 males).
      Placental restriction reduced birth weight (by 29%) and impaired glucose
      tolerance in the adult but did not affect adult adiposity, insulin secretion, or
      insulin sensitivity. Neonatal exendin-4 suppressed growth during treatment,
      followed by delayed catchup growth and unchanged adult adiposity. Neonatal
      exendin-4 partially restored glucose tolerance in PR progeny but did not affect
      insulin secretion or sensitivity. Although the effects on glucose tolerance are
      promising, the lack of effects on adult body composition, insulin secretion, and
      insulin sensitivity suggest that the neonatal period may be too late to fully
      reprogram the metabolic consequences of IUGR in species that are more mature at
      birth than rodents. 

PMID- 26219869
TI  - The use of SPECT/CT for anatomical mapping of lymphatic drainage in vulvar
      cancer: possible implications for the extent of inguinal lymph node dissection.
AB  - PURPOSE: To determine the lymphatic drainage pattern using SPECT/CT in clinically
      node-negative (cN0) patients with vulvar cancer, and to evaluate the possible
      implications for the extent of inguinal lymph node dissection. METHODS: A total
      of 83 patients with vulvar cancer scheduled for sentinel node (SN) biopsy were
      injected peritumorally with radioactive nanocolloid particles followed by
      lymphoscintigraphy and SPECT/CT for anatomical localization. The SN and higher
      echelon nodes on SPECT/CT were located in different zones in the groin and pelvic
      region. The groin was divided into five zones according to Daseler et al.: four
      zones obtained by drawing two perpendicular lines over the saphenofemoral
      junction and one zone directly overlying this junction. The nodes in the pelvic
      region were classified into three zones: external iliac/obturator, the common
      iliac and the paraaortic zones. RESULTS: A total of 217 SNs and 202 higher
      echelon nodes were localized on SPECT/CT. All SNs were located in the five zones
      according to Daseler et al.: 149 (69%) in the medial superior region, 31 (14%) in
      the medial inferior region, 22 (10%) in the central region, 14 (6.5%) in the
      lateral superior region and only 1 (0.5%) in the lateral inferior region. The
      higher-echelon nodes were located both in the groin (15%) and in the pelvic
      region (85%). CONCLUSION: In patients with cN0 vulvar cancer, lymphatic drainage
      occurs predominantly to the medial regions of the groin. Drainage to the lateral
      inferior region of the groin is only incidental and in SN-positive patients this
      zone might be spared in subsequent extended lymph node dissection. This may lead
      to a decrease in the morbidity associated with this procedure. SPECT/CT is able
      to personalize lymphatic mapping, providing detailed information about the number
      and anatomical location of SNs for adequate surgical planning in the groin.

PMID- 26219871
TI  - Textural analysis of pre-therapeutic [18F]-FET-PET and its correlation with tumor
      grade and patient survival in high-grade gliomas.
AB  - PURPOSE: Amino acid positron emission tomography (PET) with [18F]-fluoroethyl-L
      tyrosine (FET) is well established in the diagnostic work-up of malignant brain
      tumors. Analysis of FET-PET data using tumor-to-background ratios (TBR) has been
      shown to be highly valuable for the detection of viable hypermetabolic brain
      tumor tissue; however, it has not proven equally useful for tumor grading.
      Recently, textural features in 18-fluorodeoxyglucose-PET have been proposed as a
      method to quantify the heterogeneity of glucose metabolism in a variety of tumor
      entities. Herein we evaluate whether textural FET-PET features are of utility for
      grading and prognostication in patients with high-grade gliomas. METHODS: One
      hundred thirteen patients (70 men, 43 women) with histologically proven high
      grade gliomas were included in this retrospective study. All patients received
      static FET-PET scans prior to first-line therapy. TBR (max and mean), volumetric
      parameters and textural parameters based on gray-level neighborhood difference
      matrices were derived from static FET-PET images. Receiver operating
      characteristic (ROC) and discriminant function analyses were used to assess the
      value for tumor grading. Kaplan-Meier curves and univariate and multivariate Cox
      regression were employed for analysis of progression-free and overall survival.
      RESULTS: All FET-PET textural parameters showed the ability to differentiate
      between World Health Organization (WHO) grade III and IV tumors (p < 0.001; AUC
      0.775). Further improvement in discriminatory power was possible through a
      combination of texture and metabolic tumor volume, classifying 85 % of tumors
      correctly (AUC 0.830). TBR and volumetric parameters alone were correlated with
      tumor grade, but showed lower AUC values (0.644 and 0.710, respectively).
      Furthermore, a correlation of FET-PET texture but not TBR was shown with patient
      PFS and OS, proving significant in multivariate analysis as well. Volumetric
      parameters were predictive for OS, but this correlation did not hold in
      multivariate analysis. CONCLUSIONS: Determination of uptake heterogeneity in pre
      therapeutic FET-PET using textural features proved valuable for the (sub-)grading
      of high-grade glioma as well as prediction of tumor progression and patient
      survival, and showed improved performance compared to standard parameters such as
      TBR and tumor volume. Our results underscore the importance of intratumoral
      heterogeneity in the biology of high-grade glial cell tumors and may contribute
      to individual therapy planning in the future, although they must be confirmed in
      prospective studies before incorporation into clinical routine.

PMID- 26219870
TI  - Harmonizing FDG PET quantification while maintaining optimal lesion detection:
      prospective multicentre validation in 517 oncology patients.
AB  - PURPOSE: Point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction
      may improve lesion detection in oncologic PET, but can alter quantitation
      resulting in variable standardized uptake values (SUVs) between different PET
      systems. This study aims to validate a proprietary software tool (EQ.PET) to
      harmonize SUVs across different PET systems independent of the reconstruction
      algorithm used. METHODS: NEMA NU2 phantom data were used to calculate the
      appropriate filter for each PSF or PSF+TOF reconstruction from three different
      PET systems, in order to obtain EANM compliant recovery coefficients. PET data
      from 517 oncology patients were reconstructed with a PSF or PSF+TOF
      reconstruction for optimal tumour detection and an ordered subset expectation
      maximization (OSEM3D) reconstruction known to fulfil EANM guidelines. Post
      reconstruction, the proprietary filter was applied to the PSF or PSF+TOF data
      (PSFEQ or PSF+TOFEQ). SUVs for PSF or PSF+TOF and PSFEQ or PSF+TOFEQ were
      compared to SUVs for the OSEM3D reconstruction. The impact of potential
      confounders on the EQ.PET methodology including lesion and patient
      characteristics was studied, as was the adherence to imaging guidelines. RESULTS:
      For the 1380 tumour lesions studied, Bland-Altman analysis showed a mean ratio
      between PSF or PSF+TOF and OSEM3D of 1.46 (95%CI: 0.86-2.06) and 1.23 (95%CI:
      0.95-1.51) for SUVmax and SUVpeak, respectively. Application of the proprietary
      filter improved these ratios to 1.02 (95%CI: 0.88-1.16) and 1.04 (95%CI: 0.92
      1.17) for SUVmax and SUVpeak, respectively. The influence of the different
      confounding factors studied (lesion size, location, radial offset and patient's
      BMI) was less than 5%. Adherence to the European Association of Nuclear Medicine
      (EANM) guidelines for tumour imaging was good. CONCLUSION: These data indicate
      that it is not necessary to sacrifice the superior lesion detection and image
      quality achieved by newer reconstruction techniques in the quest for harmonizing
      quantitative comparability between PET systems.

PMID- 26219880
TI  - Friedreich Ataxia in Classical Galactosaemia.
AB  - Movement disorders such as ataxia are a recognized complication of classical
      galactosaemia, even in diet-compliant patients. Here, we report the coexistence
      of classical galactosaemia and Friedreich ataxia (FRDA) in nine children from
      seven Irish Traveller families. These two autosomal recessive disorders, the loci
      for which are located on either side of the centromere of chromosome 9, appear to
      be in linkage disequilibrium in this subgroup. Both conditions are known to occur
      with increased frequency amongst the Irish Traveller population.Each member of
      our cohort had been diagnosed with galactosaemia in the neonatal period, and all
      are homozygous for the common Q188R mutation in the GALT gene. Eight of the nine
      patients later presented with progressive ataxia, between the ages of 5-13 years.
      Another child presented in cardiac failure secondary to dilated cardiomyopathy at
      7 years of age. He was not ataxic at presentation and, one year from diagnosis,
      his neurological examination remains normal. The diagnosis of FRDA was confirmed
      by detecting the common pathogenic GAA expansion in both alleles of the frataxin
      gene (FXN) in each patient.Neurological symptoms are easily attributed to an
      underlying diagnosis of galactosaemia. It is important to consider a diagnosis of
      Friedreich ataxia in a child from the Irish Traveller population with
      galactosaemia who presents with ataxia or cardiomyopathy. 

PMID- 26219881
TI  - Phenotypic Expansion of Congenital Disorder of Glycosylation Due to SRD5A3 Null
      Mutation.
AB  - We present a boy, admitted at 4 months, with facial dysmorphism, hypertrichosis,
      loose skin, bilateral inguinal hernia, severe hypotonia, psychomotor disability,
      seizures with hypsarrhythmia (West syndrome), hepatosplenomegaly, increased serum
      transaminases, iris coloboma, glaucoma, corneal clouding and bilateral dilated
      lateral ventricles, and extra-axial post-cerebellar space. Serum transferrin
      isoelectrofocusing (IEF) showed a type 1 pattern. Whole-exome genotyping showed a
      previously reported homozygous nonsense mutation c.320G>A; p.Trp107X in SRD5A3.
      Epilepsy and glaucoma have been reported only once in the 19 described SRD5A3
      congenital glycosylation defect patients, and corneal clouding not at all. 

PMID- 26219882
TI  - Successful Domino Liver Transplantation from a Patient with Methylmalonic
      Acidemia.
AB  - : Liver transplantation has been reported in patients with methylmalonic acidemia
      (MMA), but long-term outcome is controversial. Many patients with other approved
      indications for liver transplantation die before donor grafts are available. A 28
      year-old man with MMA underwent cadaveric liver transplantation. His liver was
      used as a domino graft for a 61-year-old man with primary sclerosing cholangitis,
      who had low priority on the transplant waiting list. Surgical outcome was
      successful, and after transplantation both patients have excellent graft
      function. The patient with MMA showed substantial decrease in methylmalonate in
      urine (from 5,277 +/- 1,968 preoperatively to 1,068 +/- 384 mmol/mol creatinine)
      and plasma (from 445.9 +/- 257.0 to 333.3 +/- 117.7 MUmol/l) over >1-year follow
      up, while dietary protein intake increased from 0.6 to 1.36 +/- 0.33 g/kg/day.
      The domino recipient maintained near-normal levels of plasma amino acids but did
      develop elevated methylmalonate in blood and urine while receiving an
      unrestricted diet (peak plasma methylmalonate 119 MUmol/l and urine
      methylmalonate 84-209 mmol/mol creatinine, with 1.0-1.9 g/kg/day protein).
      Neither patient demonstrated any apparent symptoms of MMA or metabolic
      decompensation during the postoperative period or following discharge.
      CONCLUSION: Liver transplantation substantially corrects methylmalonate
      metabolism in MMA and greatly attenuates the disease. In this single patient
      experience, a liver from a patient with MMA functioned well as domino graft
      although it did result in subclinical methylmalonic acidemia and aciduria in the
      recipient. Patients with MMA can be considered as domino liver donors for
      patients who might otherwise spend long times waiting for liver transplantation.

PMID- 26219884
TI  - Routine testing for blood-borne viruses in prisons: a systematic review.
AB  - BACKGROUND: People in prison have a higher burden of blood-borne virus (BBV)
      infection than the general population, and prisons present an opportunity to test
      for BBVs in high-risk, underserved groups. Changes to the BBV testing policies in
      English prisons have recently been piloted. This review will enable existing
      evidence to inform policy revisions. We describe components of routine HIV,
      hepatitis B and C virus testing policies in prisons and quantify testing
      acceptance, coverage, result notification and diagnosis. METHODS: We searched
      five databases for studies of both opt-in (testing offered to all and the
      individual chooses to have the test or not) and opt-out (the individual is
      informed the test will be performed unless they actively refuse) prison BBV
      testing policies. RESULTS: Forty-four studies published between 1989 and 2013 met
      the inclusion criteria. Of these, 82% were conducted in the USA, 91% included HIV
      testing and most tested at the time of incarceration. HIV testing acceptance
      rates ranged from 22 to 98% and testing coverage from 3 to 90%. Mixed results
      were found for equity in uptake. Six studies reported reasons for declining a
      test including recent testing and fear. CONCLUSIONS: While the quality of
      evidence is mixed, this review suggests that reasonable rates of uptake can be
      achieved with opt-in and, even better, with opt-out HIV testing policies. Little
      evidence was found relating to hepatitis testing. Policies need to specify
      exclusion criteria and consider consent processes, type of test and timing of the
      testing offer to balance acceptability, competence and availability of
      individuals.

PMID- 26219885
TI  - The effect of reduced street lighting on road casualties and crime in England and
      Wales: controlled interrupted time series analysis.
AB  - BACKGROUND: Many local authorities in England and Wales have reduced street
      lighting at night to save money and reduce carbon emissions. There is no evidence
      to date on whether these reductions impact on public health. We quantified the
      effect of 4 street lighting adaptation strategies (switch off, part-night
      lighting, dimming and white light) on casualties and crime in England and Wales.
      METHODS: Observational study based on analysis of geographically coded police
      data on road traffic collisions and crime in 62 local authorities. Conditional
      Poisson models were used to analyse longitudinal changes in the counts of night
      time collisions occurring on affected roads during 2000-2013, and crime within
      census Middle Super Output Areas during 2010-2013. Effect estimates were adjusted
      for regional temporal trends in casualties and crime. RESULTS: There was no
      evidence that any street lighting adaptation strategy was associated with a
      change in collisions at night. There was significant statistical heterogeneity in
      the effects on crime estimated at police force level. Overall, there was no
      evidence for an association between the aggregate count of crime and switch off
      (RR 0.11; 95% CI 0.01 to 2.75) or part-night lighting (RR 0.96; 95% CI 0.86 to
      1.06). There was weak evidence for a reduction in the aggregate count of crime
      and dimming (RR 0.84; 95% CI 0.70 to 1.02) and white light (RR 0.89; 95% CI 0.77
      to 1.03). CONCLUSIONS: This study found little evidence of harmful effects of
      switch off, part-night lighting, dimming, or changes to white light/LEDs on road
      collisions or crime in England and Wales.

PMID- 26219886
TI  - Childhood abuse is associated with increased hair cortisol levels among urban
      pregnant women.
AB  - BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis activity is known to be
      altered following events such as childhood abuse. However, despite potential
      adverse consequences for the offspring of women who have experienced abuse, very
      little is known about altered HPA axis activity during pregnancy. METHODS: During
      pregnancy, 180 women from diverse racial/ethnic backgrounds reported on their
      exposure to emotional, physical and/or sexual abuse before the age of 11, and
      general post-traumatic stress symptoms (ie, not limited to childhood years or
      abuse experiences). Around delivery, they provided hair samples for the
      assessment of cortisol levels during pregnancy. Hair cortisol was assessed for
      each pregnancy trimester. The effect of childhood abuse on hair cortisol was
      assessed using mixed-effects analyses of covariance models allowing for within
      subject correlated observations, and were first performed in the entire sample
      and subsequently stratified by race/ethnicity. RESULTS: Controlling for post
      traumatic stress symptoms, hair cortisol levels varied by history of child abuse,
      F(2,166)=3.66, p=0.028. Childhood physical and/or sexual abuse was associated
      with greater hair cortisol levels, t(166)=2.65, p=0.009, compared with no history
      of abuse. Because childhood rates of abuse and hair cortisol levels varied by
      race/ethnicity, analyses were stratified by race/ethnicity. The associations
      between history of abuse and cortisol levels were only significant among black
      women, F(2,23)=5.37, p=0.012. CONCLUSIONS: Childhood abuse, especially physical
      and/or sexual abuse, is associated with differences in cortisol production during
      pregnancy, particularly among black women. Future research should investigate how
      these differences impact physical and mental health outcomes among offspring of
      affected women.

PMID- 26219887
TI  - The association between individual-level social capital and health: cross
      sectional, prospective cohort and fixed-effects models.
AB  - BACKGROUND: It is well known that individual-level social capital is positively
      associated with health, but most preceding studies have not fully controlled for
      an individual's time-invariant attributes, especially unobserved ones. The
      current study attempted to address how the association between individual-level
      social capital and health is confounded by an individual's unobserved time
      invariant attributes. METHODS: Data were collected from six-wave nationwide panel
      surveys conducted from 2005 to 2010, with 162,720 observations from 30,590
      individuals. Individual-level bonding and bridging social capital, as well as
      their associations with self-rated health (SRH) and psychological distress
      (measured by Kessler 6 scores), were considered. Estimation results of cross
      sectional, prospective cohort and fixed-effects logistic models were compared.
      RESULTS: The OR of reporting poor SRH responding to high bonding social capital
      rose from 0.64 (95% CI 0.62 to 0.65) in the pooled cross-sectional model to 0.77
      (0.75 to 0.80) in the prospective cohort model and 0.87 (0.82 to 0.92) in the
      fixed-effects model. Similar patterns were observed for bridging social capital,
      but the OR of reporting poor SRH became non-significant in the fixed-effects
      model. Similar results were obtained for psychological distress. CONCLUSIONS: The
      results suggest that the association between individual-level social capital and
      health is overstated by an individual's unobserved time-invariant attributes. The
      relevance of health in individual-level social capital should be assessed
      cautiously.

PMID- 26219888
TI  - Social inequality in pre-pregnancy BMI and gestational weight gain in the first
      and second pregnancy among women in Sweden.
AB  - BACKGROUND: High pre-pregnancy body mass index (BMI) and inappropriate
      gestational weight gain (GWG) are associated with adverse short and long-term
      maternal and neonatal outcomes and may act as modifiable risk factors on the path
      to overweight/obesity, but their social patterning is not well established. This
      study investigates the association of education with BMI and GWG across two
      consecutive pregnancies. METHODS: The study includes 163,352 Swedish women,
      having their first and second singleton birth in 1982-2010. In both pregnancies,
      we investigated the association of women's education with (1) pre-pregnancy
      weight status and (2) adequacy of GWG. We used multinomial logistic regression,
      adjusting for child's birth year, mother's age and smoking status. RESULTS:
      Overall, the odds of starting either pregnancy at an unhealthy BMI were higher
      among women with a low education compared to more highly-educated women. Lower
      education also predicted a greater increase in BMI between pregnancies, with this
      effect greatest among women with excessive GWG in the first pregnancy (p<0.0001
      for interaction). Education was also inversely associated with odds of excessive
      GWG in both pregnancies among healthy weight status women, but this association
      was absent or even weakly reversed among overweight and obese women. CONCLUSIONS:
      Lower educated women had the largest BMI increase between pregnancies, and these
      inequalities were greatest among women with excessive GWG in the first pregnancy.
      The importance of a healthy pre-pregnancy BMI, appropriate GWG and a healthy
      postpartum weight should be communicated to all women, which may assist in
      reducing existing social inequalities in body weight.

PMID- 26219889
TI  - Content Analysis of Social Media Related to Left Ventricular Assist Devices.
AB  - BACKGROUND: Social media have the potential to offer important benefits for
      patient education, support, and shared decision making. Despite the proliferation
      of social media use during the past decade, little is known about the scope and
      quality of available information, or the purposes that social media sites serve
      for patient decisional and support needs. METHODS AND RESULTS: We conducted a
      mixed method study, including content analysis of social media and principal
      components analysis analysis of data sites discussing left ventricular assist
      device treatment for heart failure. This study explored aspects of interactivity,
      user-friendliness, appeal, medium, purpose, audience, and accuracy of
      information. Higher levels of interactivity (eg, posting comments) seem to
      enhance the appeal and usability of available information but also introduce
      greater potential for inaccuracy and inconsistency. The current lack of oversight
      into the content and quality of available information constitute a challenge for
      the reliable use of social media as forums for information-seeking and social
      network-based support. CONCLUSIONS: We conclude that social media outlets
      constitute a promising source of informational and psychosocial support for
      patients, caregivers, and candidates, and if used in conjunction with patient
      provider dialog, can contribute to informed decision making by facilitating
      reflection and discussion of personal concerns, values, and informational needs.

PMID- 26219890
TI  - Imperatorin acts as a cisplatin sensitizer via downregulating Mcl-1 expression in
      HCC chemotherapy.
AB  - Acquisition of cisplatin resistance is the common and critical limitation for
      hepatocellular carcinoma (HCC) therapy. Our study was aimed to determine whether
      there were conditions under which the addition of imperatorin would reverse the
      resistance of HCC cells to cisplatin-based therapy. In this study, we found that
      addition of imperatorin significantly enhanced the cytotoxicity of cisplatin to
      HCC cells. Since the Mcl-1 was overexpressed in HCC cell lines (HepG2, HepG3B,
      PLC, Huh7) compared with normal liver cell line (L-O2), we found that the Mcl-1
      expression was downregulated by imperatorin but not influenced by cisplatin in
      HCC cells. In addition, our results showed the combination of imperatorin and
      cisplatin induced apoptosis and ?Psim collapse more significantly compared with
      treatment of imperatorin or cisplatin alone. Furthermore, the imperatorin-induced
      sensitization for cisplatin-cytotoxicity to HCC cells was abolished by the
      transfection of Mcl-1 expression plasmid. Finally, we found that the addition of
      imperatorin significantly reversed the resistance to cisplatin in cisplatin
      resistant HCC cells, which was Mcl-1 dependent. In summary, our study revealed
      that combination with imperatorin could enhance the antitumor activity of
      cisplatin via targeting Mcl-1 and reverse the resistance to cisplatin in HCC. 

PMID- 26219891
TI  - Dual PI3K/mTOR inhibitor, XL765 (SAR245409), shows superior effects to sole PI3K
      [XL147 (SAR245408)] or mTOR [rapamycin] inhibition in prostate cancer cell
      models.
AB  - Deregulation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B
      (Akt)/mammalian target of rapamycin (mTOR) signaling pathway contributes to
      prostate cancer development and progression. Here, we compared the in vitro
      effects of the dual PI3K/mTOR inhibitor (XL765) with those observed with the sole
      PI3K (XL147) or mTOR (rapamycin) inhibition in 2 non-tumor prostate epithelial
      cell lines, 8 prostate cancer cell lines, and 11 prostate cancer cell
      derivatives. We demonstrated that the XL765 treatment showed superior and
      proliferative effects of XL147 or rapamycin. The XL765 effects were associated to
      increasing the chromosome region maintenance 1 (CRM1)-mediated nuclear
      localization of glycogen synthase kinase 3 beta (GSK3beta) and Foxo-1a with
      higher induction of apoptosis when compared to those observed in XL147 and
      rapamycin treatments. IC50 values were calculated in phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN)-positive and PTEN-negative cell lines
      as well as after PTEN transfection or PTEN downmodulation by siRNA strategy
      revealing that the presence of this protein was associated with reduced
      sensitivity to PI3K and mTOR inhibitors. The comparison of IC50 values was also
      calculated for androgen-dependent and -independent cell lines as well as after
      androgen receptor (AR) transfection or the AR downmodulation by siRNA strategy
      revealing that androgen independence was associated with enhanced responsiveness.
      Our results provide a rationale to use the dual PI3K/Akt/mTOR inhibitors in
      hormone-insensitive prostate cancer models due to the overactivity of
      PI3K/Akt/mTOR in this disease condition. 

PMID- 26219892
TI  - Ginsenoside Rh2 inhibits invasiveness of glioblastoma through modulation of VEGF
      A.
AB  - The malignancy of glioblastoma multiforme (GBM) is largely due to its local
      invasion and the presence of the tumor in the relatively restrained region in the
      brain. Hence, effective prevention of the cancer cell invasion is substantially
      critical for controlling the growth and deterioration of GBM. We have recently
      reported the role of ginsenoside Rh2 (GRh2) in suppressing the growth of GBM
      through EGFR/PI3k/Akt/mTor signaling pathways. Here, we further showed that GRh2
      efficiently inhibited the cancer vascularization in vivo. In vitro, GRh2 dose
      dependently inhibited the protein, but not messenger RNA (mRNA) of vascular
      endothelial growth factor A (VEGF-A) in GBM cells. We then examined the
      underlying mechanisms and found that GRh2 increased the levels of miR-497, which
      bound to 3'UTR of VEGF-A mRNA to inhibit its translation. Together, our data
      demonstrate a previously unappreciated role for GRh2 in inhibition of GBM
      associated cancer vascularization, which may contribute to the effects of GRh2 on
      suppression of GBM cancer growth and invasion.

PMID- 26219893
TI  - Biological roles of microRNA-140 in tumor growth, migration, and metastasis of
      osteosarcoma in vivo and in vitro.
AB  - The objective of this study was to explore the biological roles of microRNA-140
      (miR-140) in tumor growth, migration, and metastasis of osteosarcoma (OS) in vivo
      and in vitro. Between 2007 and 2014, 47 cases of OS samples and normal bone
      tissue samples adjacent to OS were selected from our hospital. Tissue biopsies
      from OS patients were used to measure miR-140 levels to obtain a correlation
      between clinicopathological features and miR-140 expression. In vitro, MG63 human
      osteosarcoma cells were divided into four groups: blank group, miR-140 mimic
      group, miR-140 inhibitor group, and negative control (NC; empty plasmid) group.
      qRT-PCR was used to detect miR-140 expression, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay was used to detect cell proliferation,
      flow cytometry was used to detect cell cycle distribution, and scratch migration
      assay was used to detect cell migration. In vivo, the relative expression of miR
      140 level in OS tissue was lower than that in the adjacent normal bone tissue.
      miR-140 expression is inversely correlated with tumor size, Enneking stage, and
      tumor metastasis. In vitro, compared with blank group and NC group, relative miR
      140 expression was increased, cell proliferation was inhibited, cell population
      in G0/G1 phase was increased, cell population in G2/M phase and S phases and
      proliferation index (PI), and cell migration distance were decreased in the miR
      140 mimic group, but the relative expression and all the cell indexes were found
      opposite trend in the miR-140 inhibitor group. In conclusion, in vivo and vitro
      findings provided evidence that miR-140 could inhibit the growth, migration, and
      metastasis of OS cells. 

PMID- 26219894
TI  - The elevated preoperative derived neutrophil-to-lymphocyte ratio predicts poor
      clinical outcome in breast cancer patients.
AB  - Existing preclinical and clinical data suggest that the presence of a systemic
      inflammatory response plays a critical role in the progression of several solid
      tumors. The derived neutrophil-to-lymphocyte ratio (dNLR) represents an easily
      determinable marker of systemic inflammation and has been proposed as a potential
      prognostic marker. The present study was performed to validate and further
      clarify the prognostic relevance of an elevated pre-treatment dNLR in a large
      cohort of European breast cancer patients. Data from 762 consecutive female
      breast cancer patients treated from 1999 to 2004 were evaluated. Disease-free
      survival (DFS) and overall survival (OS) were assessed using the Kaplan-Meier
      method. To evaluate the prognostic relevance, univariate and multivariate Cox
      regression models were performed for each endpoint. Applying receiver operating
      characteristics (ROC) analysis, the optimal cutoff level for the dNLR was 3. In
      univariate analysis, a dNLR >=3 was associated with poor DFS (hazard ratio (HR)
      1.87, 95 % confidence interval (CI) 1.28-2.73, p = 0.001) and OS (HR 1.67, 95 %
      CI 1.07-2.63, p = 0.025). Multivariate analysis revealed a significant
      association between the elevated dNLR and poor DFS (hazard ratio (HR) 1.70, 95 %
      CI 1.09-2.65, p = 0.018) but did not show a significant association between the
      dNLR and OS (HR 1.54, 95 % CI 0.91-2.59, p = 0.106). The present study shows that
      the pre-treatment dNLR is an independent prognostic factor that could be useful
      for future individual risk assessment in breast cancer patients. 

PMID- 26219895
TI  - C14ORF166 overexpression is associated with pelvic lymph node metastasis and poor
      prognosis in uterine cervical cancer.
AB  - C14ORF166 (chromosome 14 open reading frame 166) is a transcriptional repressor
      related to the regulation of centrosome architecture. However, the role of
      C14ORF166 in the development and progression of cancer remains largely unknown.
      The aim of this study was to investigate the expression and clinicopathological
      significance of C14ORF166 in cervical cancer. C14ORF166 expression was analyzed
      using quantitative real-time PCR (RT-PCR) and Western blotting in cervical cancer
      cell lines and eight paired cervical cancer samples and the adjacent normal
      tissues. Immunohistochemistry was used to analyze C14ORF166 protein expression in
      148 clinicopathologically characterized cervical cancer specimens. Statistical
      analyses were performed to evaluate the relationship between the expression of
      C14ORF166 and clinicopathologic features and prognosis. C14ORF166 mRNA and
      protein expression were significantly upregulated in cervical cancer cell lines
      and tissue samples (P < 0.05). Immunohistochemical analysis revealed a high
      expression of C14ORF166 was observed in 39.9 % (59/148) of the cervical cancer
      specimens; the remaining samples expressed low levels or did not express any
      detectable C14ORF166. The chi-square test indicated that high-level expression of
      C14ORF166 was significantly associated with International Federation of
      Gynecology and Obstetrics (FIGO) stage (P < 0.001), vital status (P = 0.026),
      tumor size (P = 0.034), serum squamous cell carcinoma antigen level (SCC-Ag; P =
      0.035), and pelvic lymph node metastasis (P < 0.001). Patients with highly
      expressed C14ORF166 showed a tendency to receive postoperative chemotherapy (P =
      0.005) and postoperative radiation (P = 0.008). Furthermore, high C14ORF166
      expression was associated with poorer overall survival compared to low C14ORF166
      expression, and C14ORF166 was a significant prognostic factor in univariate and
      multivariate analysis (P < 0.05). High C14ORF166 expression had prognostic value
      for poor outcome in cervical cancer. C14ORF166 may represent a biomarker of
      pelvic lymph node metastasis and enable the identification of high-risk patients
      along with selection of appropriate treatment strategies. 

PMID- 26219896
TI  - Transforming acidic coiled-coil-containing protein 3 (TACC3) overexpression in
      hepatocellular carcinomas is associated with "stemness" and epithelial
      mesenchymal transition-related marker expression and a poor prognosis.
AB  - There is accumulating evidence that hepatocellular carcinomas (HCCs) expressing
      "stemness"-related markers, e.g., keratin 19 (K19) and epithelial cell adhesion
      molecule (EpCAM), are associated with aggressive biological behavior. In order to
      further investigate the molecular characteristics of this subgroup of HCCs, we
      examined copy number alterations of K19-positive and K19-negative HCCs and found
      frequent amplifications of the 4p16.3 locus containing the TACC3 gene, which has
      previously not been described in HCCs. We performed an immunohistochemical
      analysis of transforming acidic coiled-coil-containing protein 3 (TACC3)
      expression in HCCs in whole tissue sections and tissue microarrays and examined
      the clinicopathological characteristics of TACC3-overexpressing HCCs in relation
      to stemness-related marker (K19, EpCAM) expression, epithelial-mesenchymal
      transition (EMT)-related proteins, and survival. Cytoplasmic TACC3 protein
      expression was seen in 7/7 whole tissue sections of K19-positive HCCs, while
      TACC3 expression was negative or patchy in K19-negative cases. In the tissue
      microarray cohort, TACC3 was overexpressed in 105/188 (55.9 %) HCCs and was
      associated with poor differentiation (p = 0.028), major vascular invasion (p =
      0.039), higher tumor stages (p = 0.015), younger age (p = 0.003), higher
      proliferative activity (p < 0.001), and more frequent multipolar mitoses (p <
      0.001). TACC3 expression was significantly correlated with K19 (p = 0.010) and
      EpCAM (p < 0.001) positivity. In addition, TACC3 overexpression was associated
      with frequent expression of S100A4, uPAR, and ezrin (p < 0.001, all) and loss of
      E-cadherin expression (p = 0.014), and overall survival was significantly
      decreased in patients with TACC3-positive HCCs (p = 0.014). In conclusion, TACC3
      overexpression was associated with clinicopathological features of
      aggressiveness, increased EMT-related protein expression, and poor survival,
      suggesting a potential role for TACC3 as a prognostic biomarker and therapeutic
      target in HCC. 

PMID- 26219897
TI  - E-cadherin increasing multidrug resistance protein 1 via hypoxia-inducible factor
      1alpha contributes to multicellular resistance in colorectal cancer.
AB  - When cancer cells have been cultured as three-dimensional (3D) cultures or in
      vivo, they decrease sensitivity to anticancer drugs. This is called multicellular
      resistance, and the mechanism is not fully understood. Here, we report that E
      cadherin increasing multidrug resistance protein 1 (MDR1) via hypoxia-inducible
      factor-1alpha (HIF-1alpha) contributes to multicellular resistance in colorectal
      cancer. The MDR1 protein level was higher in 3D cultures than in monolayer cells.
      When dispersed cells from 3D cultures were grown as monolayer cells again, the
      MDR1 protein level decreased to the similar level of cells maintained as
      monolayer all through. Knockdown of MDR1 significantly decreased multicellular
      resistance. Knockdown of E-cadherin decreased MDR1 in 3D cultures but did not
      detectably change MDR1 in monolayer cells. E-cadherin was expressed uniformly in
      3D cultures while the MDR1 protein level was higher in the center of 3D cultures
      than in the peripheral part. Knockdown of E-cadherin decreased E-cadherin
      uniformly in 3D cultures but mainly decreased MDR1 at the center of 3D cultures.
      These suggest that knockdown of E-cadherin decreasing MDR1 may be by an indirect
      mechanism. HIF-1alpha was remarkably increased in 3D cultures. Knockdown of E
      cadherin decreased intercellular junctions, increased intercellular space, and
      decreased HIF-1alpha in 3D cultures. Knockdown of HIF-1alpha decreased MDR1 in 3D
      cultures. Knockdown of E-cadherin increased beta-catenin uniformly in 3D
      cultures, and knockdown of beta-catenin decreased MDR1 what was opposite to
      knockdown of E-cadherin decreasing MDR1. Our data reveal that knockdown of E
      cadherin decreasing MDR1 via HIF-1alpha is involved in the mechanism of
      multicellular resistance in colorectal cancer. Though beta-catenin is also
      involved in the mechanism, it does not play a dominant role. 

PMID- 26219899
TI  - CCR7 regulates Twist to induce the epithelial-mesenchymal transition in
      pancreatic ductal adenocarcinoma.
AB  - As reported, the CC chemokine receptor 7 (CCR7) trigger a series of signaling
      cascades in the epithelial-mesenchymal transition (EMT) of some malignancies.
      Meanwhile, Twist promotes EMT in pancreatic ductal adenocarcinoma (PDAC)
      progression. Here, effects of Twist on CCR7-induced EMT in the PDAC were
      investigated in detail. The immunohistochemistry was used to detect the
      expression of Twist, and then, in vitro assays were applied. The expression rate
      of Twist was 72.0 % in PDAC samples and closely correlated with tumor-node
      metastasis (TNM) stage and invasion. When PDAC cell line PANC1 was subjected to
      CCL19 stimulation, the expression of p-ERK, p-AKT, Twist, N-cadherin, MMP9, and
      alpha-smooth muscle actin (alpha-SMA) was induced, while the GSK1120212, BEZ235,
      and MK2206 prohibited the increase of Twist and EMT biomarkers. For another
      thing, the si-Twist treatment attenuated CCL19-stimulated EMT occurrence,
      migration, and invasion phenotypes of PANC1 cells. In conclusion, CCR7 pathway up
      regulates Twist expression via ERK and PI3K/AKT signaling to manage the EMT of
      PDAC. Our work allows for clinical gene or protein-targeted regimen of PDAC
      patients in the near future. 

PMID- 26219898
TI  - 2ME2 inhibits the activated hypoxia-inducible pathways by cabozantinib and
      enhances its efficacy against medullary thyroid carcinoma.
AB  - Cabozantinib is a multi-targeted tyrosine kinase inhibitor targeting vascular
      endothelial growth factor (VEGF) receptor (VEGFR)-2, MET (c-Met, also called
      hepatocyte growth factor (HGF) receptor), and other receptor tyrosine kinases.
      Cabozantinib has recently been approved for treating advanced medullary thyroid
      carcinoma (MTC), but its long-term benefit remains uncertain and dose-dependent
      adverse events are very common. The present study has demonstrated that 2
      methoxyestradiol (2ME2), an inhibitor of hypoxia-inducible factors (HIFs) and a
      promising anticancer agent under investigation in clinical trials, strengthens
      anticancer activities of cabozantinib against MTC cells in vitro and in vivo. The
      activated hypoxia-inducible pathways, which are mainly regulated by HIF-1,
      contribute to the resistance of hypoxic MTC cells to cabozantinib. Cabozantinib
      upregulated HIF-1alpha expression at translational levels and increased the
      expression of the downstream factors including VEGF, lactate dehydrogenase A
      (LDHA), HGF, and MET. 2ME2 corrected the activated pathways by cabozantinib
      through downregulating HIF-1alpha expression and inhibiting its nuclear
      translocation in hypoxic MTC cells. Administration of 2ME2 enhanced the efficacy
      of cabozantinib in suppressing the growth of MTC cell line xenografts and patient
      derived xenografts established in mice. Given that 2ME2 targets insensitive
      hypoxic cancer cells to cabozantinib and can inhibit the activated pathways by
      cabozantinib, the present results warrant further investigation of 2ME2,
      particularly in combination with cabozantinib, for the treatment of MTC. 

PMID- 26219900
TI  - Co-expression and clinical utility of Snail and N-cadherin in papillary thyroid
      carcinoma.
AB  - Papillary thyroid carcinoma is one of the most common subtypes of thyroid cancer
      and portends a good prognosis. N-cadherin (neural cadherin) is a member of the
      classical cadherin family and is often overexpressed in many types of cancers.
      Snail, a kind of zinc finger protein, is a transcriptional repressor which has
      been intensively studied in mammals. We investigate the immunohistochemical
      expression of Snail and N-cadherin in papillary thyroid carcinoma tissues and
      cells and then discuss the clinical value of Snail and N-cadherin expression.
      Immunohistochemical technique was performed to detect Snail and N-cadherin in 60
      cases of papillary thyroid carcinoma and analyzed the relationship between the
      expression of Snail, N-cadherin, and clinicopathological indicators. Western blot
      was used to investigate the constitutive and inducible expression of Snail and N
      cadherin. In our study, the expression rate of Snail and N-cadherin was 85.0 %
      (51/60) and 78.3 % (47/60), respectively, in papillary thyroid carcinoma. The
      expression rate of Snail and N-cadherin in thyroid papillary carcinoma with
      metastatic lymph nodes was 93.3 and 86.7 %, respectively, while in papillary
      thyroid carcinoma tissue without lymph node metastasis, the expression rate was
      60.0 and 53.3 %, respectively. The positive correlation of Snail and N-cadherin
      was observed (r = 0.721, p < 0.01). In addition, Western blot further identified
      the constitutive and inducible expression of Snail and N-cadherin in papillary
      thyroid carcinoma tissues and cell lines. In conclusion, Snail and N-cadherin are
      constitutively and inducibly expressed in papillary thyroid carcinoma and may
      play important roles in the development and metastasis of papillary thyroid
      carcinoma. Snail and N-cadherin may be used as an effective indicator. 

PMID- 26219902
TI  - One shot of carbon-ion radiotherapy cured a 6-cm chemo-resistant metastatic liver
      tumor: a case of breast cancer.
AB  - The standard treatment for metastatic liver tumor from breast cancer is systemic
      medical treatment, and there is controversy regarding the value of local
      treatment. However, there are some exceptional cases that do benefit from local
      therapy. We describe the case of a 54-year-old woman with systemic therapy
      resistant liver metastasis from breast cancer successfully treated with a single
      shot of 36-GyE carbon-ion radiotherapy and surviving more than 8 years without
      local recurrence. This case represents a good example of the usefulness and
      safety of carbon-ion radiotherapy, and who might benefit from local therapy. 

PMID- 26219901
TI  - Clinical significance of serum interleukin-29, interleukin-32, and tumor necrosis
      factor alpha levels in patients with gastric cancer.
AB  - Many studies suggested that cytokines interleukin (IL)-29, IL-32, and tumor
      necrosis factor alpha (TNF-alpha) are implicated in the pathogenesis of
      malignancies. The purpose of this study was to determine the clinical
      significance of the serum levels of IL-29, IL-32, and TNF-alpha in gastric cancer
      (GC) patients. Fifty-eight GC patients and 20 age- and sex-matched healthy
      controls were enrolled into this study. The median age at diagnosis was 59.5
      years (range 32-82 years). Tumor localization of the majority of the patients was
      antrum (n = 42, 72.4 %), and tumor histopathology of the majority of the patients
      was diffuse (n = 43, 74.1 %). The majority of the patients had stage IV disease
      (n = 41, 70.7 %). Thirty-six (62.1 %) patients had lymph node involvement. The
      median follow-up time was 66 months (range 1 to 97.2 months). The baseline serum
      IL-29 concentrations were not different between patients and controls (p =
      0.627). The baseline serum IL-32 and TNF-alpha concentrations of the GC patients
      were significantly higher (for IL-32, p = 0.014; for TNF-alpha, p = 0.001).
      Gender, localization, histopathology, tumor, and lymph node involvement were not
      found to be correlated with serum IL-29, IL-32, and TNF-alpha concentrations (p >
      0.05). Patients without metastasis (p = 0.01) and patients who responded to
      chemotherapy (p = 0.04) had higher serum IL-29 concentrations. Patients older
      than 60 years had higher serum IL-32 (p = 0.002). Serum IL-29, IL-32, and TNF
      alpha levels were not associated with outcome (p = 0.30, p = 0.51, and p = 0.41,
      respectively). In conclusion, serum levels of IL-32 and TNF-alpha may be
      diagnostic markers, and serum IL-29 levels may be associated with good prognosis
      in patients with GC. 

PMID- 26219903
TI  - Changes in radiological imaging frequencies in children before and after the
      accident at the Fukushima Daiichi Nuclear Power Plant in Fukushima Prefecture,
      Japan.
AB  - PURPOSE: The accident at the Fukushima Daiichi Nuclear Power Plant has raised
      concerns about radiation exposure, including medical radiation exposure such as X
      ray and CT, in residents of Fukushima. MATERIALS AND METHODS: We compared the
      numbers and the ratio of outpatients less than 10 years old who underwent imaging
      examinations [e.g., CT, X-ray, MRI, ultrasonography (US), etc.] at Fukushima
      Medical University hospital in Fukushima, Japan before (April 1, 2008-March 31,
      2011) and after (April 1, 2011-March 31, 2014) the accident. RESULTS: The number
      of outpatients less than 10 years old decreased after the accident. The number of
      outpatients less than 10 years old who underwent CT and X-ray examinations also
      significantly decreased after the accident (p < 0.001, p < 0.01, respectively).
      CONCLUSION: Our results suggest that the number of pediatric radiological
      examinations decreased after the accident in Fukushima. We should continue to
      communicate with patients and their families to ensure that they understand the
      risks and benefits of radiological imaging in order to overcome their concerns
      about the nuclear disaster.

PMID- 26219904
TI  - Modeling of switching mechanism in GeSbTe chalcogenide superlattices.
AB  - We study the switching process in chalcogenide superlattice (CSL) phase-change
      memory materials by describing the motion of an atomic layer between the low and
      high resistance states. Two models have been proposed by different groups based
      on high-resolution electron microscope images. Model 1 proposes a transition from
      Ferro to Inverted Petrov state. Model 2 proposes a switch between Petrov and
      Inverted Petrov states. For each case, we note that the main transition is
      actually a vertical displacement of a Ge layer through a Te layer, followed by a
      lateral motion of GeTe sublayer to the final, low energy structure. Through
      calculating energy barriers, the rate-determining step is the displacive
      transition. 

PMID- 26219905
TI  - Dyslipidemia in Overweight and Obese School-Aged Children.
AB  - Dyslipidemia often affects overweight and obese adolescents and can be present
      along with hypertension, insulin resistance, type 2 diabetes, and polycystic
      ovarian syndrome. This article is the third of six discussing the comorbidities
      of childhood obesity and will focus on the individual parts of the lipid profile
      and the impact of dyslipidemia on the heart and other body systems. Since few
      pharmacologic therapies are approved to treat dyslipidemia in children and
      adolescents younger than 18, treatment consists of lifestyle changes that can be
      supported and modeled by the school nurse. The school nurse can also be an
      advocate for a healthy lifestyle in the school district and community. More
      success in the treatment of dyslipidemia will be realized with less attention to
      changing the individual and more attention to changing the wider populations,
      including schools and the community. 

PMID- 26219906
TI  - School Nurse Workload: Students Are More Than Just Numbers.
AB  - NASN has found a lack of research-based evidence to support the caseload ratio
      model of school nurse staffing. In keeping with the practices of school
      administrators, other school support personnel, and community health care
      providers, NASN is transitioning to the workload model to guide safe school nurse
      staffing. The workload model considers more than ratio and acuity; instead, it
      provides a full description of school nurse activities and other influences on
      student health. 

PMID- 26219907
TI  - Autoinflammation Around AES Total Ankle Replacement Implants.
AB  - BACKGROUND: Failure of total ankle replacement (TAR) can be characterized by
      early peri-implant osteolysis even in the presence of very modest numbers of wear
      particles. The hypothesis of the study was that this reaction is in part mediated
      by autoinflammatory responses mediated via damage-associated molecular patterns
      (DAMPs, danger signals) and pattern-recognizing danger signal receptors (PRRs).
      METHODS: Peri-implant tissue and control samples from 10 patients with AES
      implants were immunostained for hypoxia inducible factor-1alpha (HIF-1alpha),
      activated caspase-3, high-mobility group box 1 (HMGB1), receptor for advanced
      glycation end product (RAGE), and toll-like receptors TLR2 and TLR4. Results were
      evaluated on a 0 to 4 scale (from 0% to >50% stained area). RESULTS: Peri-implant
      tissue around failed TAR implants had a relatively high mean HIF-1alpha score of
      3 on a scale, which however was similar in control samples. HMGB1 (a DAMP) was
      seen to be mobilized from nuclei to cellular cytoplasm, and the active caspase
      3(+) cells were increased. All PRRs were increased in revision samples.
      CONCLUSIONS: Increased expression of HMGB1 and other danger signals together with
      increased PRR-dependent responsiveness could contribute to autoinflammatory peri
      implantitis, multilocular cyst formation, and osteolysis in failed TAR implants.
      LEVEL OF EVIDENCE: Level IV, case series.

PMID- 26219908
TI  - Feasibility and Safety of an Operative Tool for Anterior Chronic Exertional
      Compartment Syndrome Treatment.
AB  - BACKGROUND: Operative management of chronic exertional compartment syndrome of
      the tibialis anterior muscle compartment (ant-CECS) usually involves the use of a
      fasciotome. Collateral tissue damage such as hematoma and nerve damage may occur
      during the procedure. The current report assessed the feasibility and safety of
      an alternative tool for the operative management of ant-CECS. METHODS: The system
      had a speculum-like hollow tube that was inserted via a 2-cm skin incision and
      allowed for the protected advancement of a fasciotome. The device was tested in
      patients with bilateral ant-CECS. Symptoms were prospectively scored before and
      after surgery using a 5-category verbal rating scale (VRS). Fourteen patients
      (age 26 +/- 10 years) were analyzed. Complications and operative efficacy were
      determined using physical examination and questionnaires after 21 (range = 16-25)
      months. RESULTS: Technical operative success rate was 100% (28/28 legs).
      Operation time was 10 +/- 2 minutes per leg (range = 6-14). Perioperative
      complications were not observed. One superficial wound infection was treated
      nonoperatively. Significant reductions in pain (-2.2 +/- 1.1 on 5-point VRS, P <
      .001), tightness (-1.9 +/- 1.6, P = .01), cramps (-1.4 +/- 1.6, P = .009), muscle
      weakness (-1.6 +/- 1.2, P < .001), and altered sensibility (-1.3 +/- 1.4, P =
      .005) were registered 21 months postoperatively. CONCLUSION: This fasciotome was
      simple to use and allowed for a safe fasciotomy in patients with leg ant-CECS. A
      randomized controlled trial comparing the present device with a widely used
      fasciotome was under way at the time of writing of this study.

PMID- 26219909
TI  - Circulating CD4(+) CD25(high) FoxP3(+) T-regulatory cells in patients with atopic
      dermatitis after narrowband-ultraviolet B phototherapy.
AB  - BACKGROUND: Previous studies showed controversial results regarding CD4(+)
      CD25(high) FoxP3(+) T-regulatory cells (Tregs) in atopic dermatitis (AD) and
      effect of therapy. METHODS: Circulating CD4(+) CD25(high) FoxP3(+) Tregs were
      assessed by flow cytometry in 20 controls and 20 patients with AD at baseline and
      after narrowband ultraviolet B with assessment of disease severity. RESULTS:
      Patients showed higher pretreatment T-effector cells (Teffs) (%) and lower
      pretreatment Tregs FoxP3 expression% than controls (P = 0.003 and 0.01,
      respectively). Mild AD showed a lower Tregs/Teffs ratio compared to controls (P =
      0.013), while moderate group showed higher Teffs%, and lower Tregs FoxP3
      expression% and Tregs/Teffs compared to controls (P = 0.016, 0.007, and 0.009
      respectively). The severe group had higher Tregs% and Teffs%, yet with a lower
      Tregs FoxP3 expression% compared to controls (P < 0.001, P = 0.043, P = 0.044,
      respectively). There was significant reduction of severity after narrowband
      ultraviolet B (P = 0.007), with overall significant elevation of Tregs FoxP3
      expression% in patients (P = 0.004). All patients' post-treatment laboratory
      findings were statistically matched to each other and to controls whatever their
      previous severity or therapeutic response. The improvement of severity score
      correlated with the change in both Tregs% and Tregs/Teffs. CONCLUSIONS:
      Significant reduction in AD disease severity is correlated with the change in
      Tregs% and Tregs/Teffs.

PMID- 26219910
TI  - [Not Available].

PMID- 26219911
TI  - [Better apprehension of errors in the early clinical treatment of the severely
      injured].
AB  - BACKGROUND: Every year preventable adverse events endanger a considerable number
      of patients. Current guidelines of the Federal Joint Committee require clinical
      quality management to provide amongst others an independent clinical risk
      management and a critical incident reporting system (CIRS). Such guidelines
      increase the pressure to actively deal with errors, even in emergency medicine.
      Human error is considered to be the main cause of preventable adverse events in
      high-risk industries, such as aviation. This observation is gladly directly
      transferred to clinical medicine. OBJECTIVES: This study investigated where the
      true causes for preventable adverse events during the resuscitation of severely
      injured patients can be found. METHODS: A non-systematic literature search of the
      PubMed database was performed. RESULTS: The search identified three recent
      studies addressing these objectives that revealed human error as the most
      important cause of preventable adverse events during emergency room resuscitation
      (88-97%). Errors during resuscitation in the emergency room occur in
      approximately 10 %. It is striking that such data do not differ greatly from
      findings described in studies undertaken 20 years ago. One possible explanation
      might be that the systematic evaluation of medical errors in the emergency room
      is a weak spot and that too few lessons can be learnt from such incidents.
      Therefore, this article describes models of error development and outlines
      methods to collect data for root cause analysis and for clinical risk management.
      Thus, this review aims at a better understanding of how errors originate and to
      allow development of strategies to prevent errors from happening again.
      CONCLUSION: Human error is the most important cause of preventable adverse events
      during emergency room resuscitation. Presumably, errors occur unintentionally and
      as a result of situational misjudgment. As such errors have marked consequences
      on mortality and morbidity of severely injured patients, an extensive risk
      management is mandatory for the improvement of quality and safety. Appropriate
      methods to record errors in order to allow a correct root cause analysis
      according to well-established protocols is a basic prerequisite.

PMID- 26219912
TI  - Aspirin Targets SIRT1 and AMPK to Induce Senescence of Colorectal Carcinoma
      Cells.
AB  - Cancer therapies attempt to destroy the entire tumor, but this tends to require
      toxic compounds and high doses of radiation. Recently, considerable attention has
      focused on therapy-induced senescence (TIS), which can be induced in cancer cells
      by low doses of therapeutic drugs or radiation and provides a barrier to tumor
      development. However, the molecular mechanisms governing TIS remain elusive.
      Special attention has been paid to the potential chemopreventive effect of
      aspirin against human colorectal cancer. In this study, we investigated the
      effects of aspirin on TIS of human colorectal carcinoma (CRC) cells and show that
      it occurs via sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK), two key
      regulators of cellular metabolism. Aspirin increased the senescence of CRC cells,
      increased the protein levels of SIRT1, phospho-AMPK (T172), and phospho-acetyl
      CoA carboxylase (S79), and reduced the cellular level of ATP. Small-interfering
      RNA-mediated downregulation or pharmacological inhibition of SIRT1 or AMPK
      significantly attenuated the aspirin-induced cellular senescence in CRC cells. In
      contrast, treatment with a SIRT1 agonist or an AMP analog induced cellular
      senescence. Remarkably, SIRT1 knockdown abrogated the aspirin-induced activation
      of AMPK, and vice versa. During the progression of aspirin-induced cellular
      senescence in CRC cells, SIRT1 showed increased deacetylase activity at a
      relatively early time point but was characterized by decreased activity with
      increased cytoplasmic localization at a later time point. Collectively, these
      novel findings suggest that aspirin could provide anticancer effects by inducing
      senescence in human CRC cells through the reciprocal regulation of SIRT1-AMPK
      pathways. 

PMID- 26219913
TI  - Suppression of Cytosolic NADPH Pool by Thionicotinamide Increases Oxidative
      Stress and Synergizes with Chemotherapy.
AB  - NAD(+) kinase (NADK) is the only known cytosolic enzyme that converts NAD(+) to
      NADP(+), which is subsequently reduced to NADPH. The demand for NADPH in cancer
      cells is elevated as reducing equivalents are required for the high levels of
      nucleotide, protein, and fatty acid synthesis found in proliferating cells as
      well as for neutralizing high levels of reactive oxygen species (ROS). We
      determined whether inhibition of NADK activity is a valid anticancer strategy
      alone and in combination with chemotherapeutic drugs known to induce ROS. In
      vitro and in vivo inhibition of NADK with either small-hairpin RNA or
      thionicotinamide inhibited proliferation. Thionicotinamide enhanced the ROS
      produced by several chemotherapeutic drugs and produced synergistic cell kill.
      NADK inhibitors alone or in combination with drugs that increase ROS-mediated
      stress may represent an efficacious antitumor combination and should be explored
      further. 

PMID- 26219914
TI  - Prognostic factors in patients with metastatic spinal cord compression secondary
      to lung cancer: a systematic review of the literature.
AB  - PURPOSE: The Metastatic spinal cord compression (MSCC) secondary to lung cancer
      (LC) has worse prognosis when compared to MSCC related to other solid tumors. The
      purpose of this study is to identify the survival time and the prognostic factors
      in the MSCC secondary to LC. METHODS: A systematic review of the literature has
      been carried out. Studies published between January 2005 and March 2015 were
      identified through the electronic database PubMed and LILACS. Two independent
      reviewers selected the articles. RESULTS: 7 studies were identified, which met
      the inclusion criteria, involving 1010 patients. The survival in 6 and 12 months
      ranged between 18 and 61%, and between 3.8 and 32%, respectively. The median
      survival ranged between 2.8 and 9 months. The variables related to the survival
      improvement were: female, performance status 1 or 2, pre-radiotherapy and
      postoperative ambulatory status, absence of bone metastases and visceral
      metastases, interval from cancer diagnosis to spinal metastases or radiotherapy
      of MSCC>15 months, slower (>7 days) development of motor deficit, and the
      neurological status at the postoperative. CONCLUSIONS: The prognosis of the MSCC
      secondary to LC was poor. Considering the small number of studies identified,
      further research is needed to identify prognostic factors that are independent of
      the MSCC secondary to LC.

PMID- 26219915
TI  - CT accuracy of percutaneous versus open pedicle screw techniques: a series of
      1609 screws.
AB  - INTRODUCTION: Traditional open exposure for posterior instrumentation requires
      significant soft tissue mobilization and causes significant blood loss and
      increased recovery time. Mal-placed screws can injure nerve roots, the spinal
      cord, viscera, vasculature and the cardiopulmonary system. Placement of pedicle
      screws using a minimally invasive technique can decrease bleeding risk, damage to
      soft tissues, and post-operative pain. The purpose of this study is to compare
      the radiographic accuracy of open free-hand versus percutaneous technique for
      pedicle screw placement. METHODS: Consecutive patients undergoing thoracolumbar
      surgery from September 2006 to October 2011 with post-operative CT imaging were
      included in this study. Three-dimensional screw positioning within the pedicle
      and the vertebral body was assessed on CT. The magnitude and location of
      violations were measured and recorded. Facet breaches at the cephalad and caudad
      ends of the construct were documented and graded. RESULTS: Two-hundred and twenty
      three patients met the inclusion criteria for a total of 1609 pedicle screws.
      Seven-hundred and twenty-four screws were placed using a standard open free-hand
      technique and 885 were placed percutaneously. There was a significant difference
      in overall pedicle breach rates: 7.5 % for open and 4.7 % for percutaneous
      techniques. The magnitude of breach was greater for the percutaneous technique
      compared to the open technique: 5.4 versus 3.7 mm, respectively. The difference
      in vertebral body breaches was also significant: 11.3 % for open and 3.6 % for
      percutaneous. The rates of facet breach did not significantly differ. DISCUSSION
      AND CONCLUSION: This is the largest series comparing the accuracy of percutaneous
      to open pedicle screw placement. The rates of pedicle, vertebral body, and facets
      breaches in the percutaneous group were similar to the rates in the open
      technique group as well as rates reported in the literature. This demonstrates
      that the percutaneous technique described here is an accurate alternative to
      standard open free-hand technique.

PMID- 26219916
TI  - Chest wall reconstruction after en bloc Pancoast tumour resection with the use of
      MatrixRib and SILC fixation systems: technical note.
AB  - STUDY DESIGN: Technical note. OBJECTIVE: In cases in which partial resection of
      the rib cage is accomplished with vertebrectomy, reconstruction of the chest wall
      may be challenging. That is because of lack of the anchor point which normally
      would be a proximal end of a rib or transverse process. We report a
      straightforward technique for chest wall reconstruction with the novel use of two
      systems of fixation commonly applied in spinal practice. METHODS: The operation
      of a squamous cell carcinoma (Pancoast tumour) of the right lung infiltrating T2,
      T3 and T4 vertebrae was performed though T4 lateral thoracotomy. Posterior
      instrumentation with transpedicular screws T1-3-5 on the left and T1-5 on the
      right side was followed with the right upper lobectomy and hemivertebrectomy. The
      laminae and facet joints of T2-T4 vertebrae were removed on the side of the
      tumour. An osteotomy was performed medial to the pedicle at the lateral aspect of
      the dural sac on the side of the tumour. Proximal parts of four adjacent ribs
      were removed allowing radical en bloc resection with tumour-free margins. The
      distal end of each of four rib plates used (MatrixRib Precontoured Plate system)
      was attached to the proximal end of the rib. The proximal end of the plate was
      then attached to the rod of posterior fixation construct with the use of a
      flexible polyethylene terephthalate (PeT) band of the SILCTM fixation system. The
      other end of the PeT band was then passed through the top-loading clamp
      subsequently attached to the rod of the posterior fixation. RESULTS: The patient
      did not require additional procedures for chest wall reconstruction. On the 7
      month follow-up, in chest CT he was found with satisfactory expansion of the
      remaining lung tissue with proper spinal alignment and anatomical shape of the
      rib cage. CONCLUSIONS: The reported technique can be applied for chest wall
      reconstruction in cases of total or subtotal vertebrectomy accomplished with the
      resection extending towards rib cage. It appears to be straightforward, safe and
      effective allowing good cosmetic and functional outcome.

PMID- 26219918
TI  - Advances in hepatitis C therapies.
AB  - INTRODUCTION: The recent development of new direct acting antivirals constitutes
      a clinical revolution in the field of hepatitis C therapy. Different drugs with
      direct antiviral effects and very high potency have been developed, changing the
      current scenario and prognosis of hepatitis C-related liver disease. This review
      aims to clarify the current stage of the different antiviral strategies in
      patients with chronic hepatitis C infection by analyzing the specific efficacy of
      each combination. AREAS COVERED: Data have been extracted from the most important
      published clinical trials, cumulative real-world experience reports and data from
      the most relevant studies presented in the last international meetings (European
      and American International Liver Congresses). In addition, data from the recently
      updated international guidelines have also been included. EXPERT OPINION:
      Although there are many differences in health-care budgets among countries in the
      world which will surely compromise drug availability and treatment decisions,
      this review aims to give a general and brief recommendation to help treating
      physicians to choose the best option to treat hepatitis C.

PMID- 26219917
TI  - Glucose deprivation increases tau phosphorylation via P38 mitogen-activated
      protein kinase.
AB  - Alterations of glucose metabolism have been observed in Alzheimer's disease (AD)
      brain. Previous studies showed that glucose deprivation increases amyloidogenesis
      via a BACE-1-dependent mechanism. However, no data are available on the effect
      that this condition may have on tau phosphorylation. In this study, we exposed
      neuronal cells to a glucose-free medium and investigated the effect on tau
      phosphorylation. Compared with controls, cells incubated in the absence of
      glucose had a significant increase in tau phosphorylation at epitopes
      Ser202/Thr205 and Ser404, which was associated with a selective activation of the
      P38 mitogen-activated protein kinase. Pharmacological inhibition of this kinase
      prevented the increase in tau phosphorylation, while fluorescence studies
      revealed its co-localization with phosphorylated tau. The activation of P38 was
      secondary to the action of the apoptosis signal-regulating kinase 1, as its down
      regulation prevented it. Finally, glucose deprivation induced cell apoptosis,
      which was associated with a significant increase in both caspase 3 and caspase 12
      active forms. Taken together, our studies reveal a new mechanism whereby glucose
      deprivation can modulate AD pathogenesis by influencing tau phosphorylation and
      suggest that this pathway may be a new therapeutic target for AD. 

PMID- 26219919
TI  - Simultaneous realization of Hg(2+) sensing, magnetic resonance imaging and
      upconversion luminescence in vitro and in vivo bioimaging based on hollow
      mesoporous silica coated UCNPs and ruthenium complex.
AB  - We have constructed a multifunctional nanoprobe with sensing and imaging
      properties by using hollow mesoporous silica coated upconversion nanoparticles
      (UCNPs) and Hg(2+) responsive ruthenium (Ru) complex. The Ru complex was loaded
      into the hollow mesoporous silica and the UCNPs acted as an energy donor,
      transferring luminescence energy to the Ru complex. Furthermore, polyethylenimine
      (PEI) was assembled on the surface of mesoporous silica to achieve better
      hydrophilic and bio-compatibility. Upon addition of Hg(2+), a blue shift of the
      absorption peak of the Ru complex is observed and the energy transfer process
      between the UCNPs and the Ru complex was blocked, resulting in an increase of the
      green emission intensity of the UCNPs. The un-changed 801 nm emission of the
      nanoprobe was used as an internal standard reference and the detection limit of
      Hg(2+) was determined to be 0.16 MUM for this nanoprobe in aqueous solution. In
      addition, based on the low cytotoxicity as studied by CCK-8 assay, the nanoprobe
      was successfully applied for cell imaging and small animal imaging. Furthermore,
      when doped with Gd(3+) ions, the nanoprobe was successfully applied to in vivo
      magnetic resonance imaging (MRI) of Kunming mice, which demonstrates its
      potential as a MRI positive-contrast agent. Therefore, the method and results may
      provide more exciting opportunities to afford nanoprobes with multimodal
      bioimaging and multifunctional applications. 

PMID- 26219921
TI  - Differential in situ expression of insulin-like growth factor-1 receptor in
      different histological subtypes of basal cell carcinoma: An immunohistochemical
      investigation.

PMID- 26219920
TI  - Interleukin-2 Production by Cultured Human Granulosa Cells.
AB  - PROBLEM: Ovarian hyperstimulation syndrome (OHSS) is similar to vascular leak
      syndrome (VLS), which may be attributable to the massive increase in systemic
      inflammatory cytokines. The hyperstimulated human ovaries were demonstrated to
      contain interleukin (IL)-2, which, in turn, was suggested to activate the
      systemic inflammatory response characteristic of OHSS. As the source of
      follicular fluid IL-2 is still unclear, in the present study, we sought to
      validate the presence of IL-2 and IL-2 mRNA expression in human luteinized
      granulosa cells. METHOD OF STUDY: IL-2 nuclear expression was detected using real
      time PCR and immunofluorescence staining of human luteinized granulosa cell from
      6 patients undergoing in vitro fertilization treatment. Calretinin
      immunofluorescence staining was used as a marker of granulosa cells. RESULTS: IL
      2-positive immunofluorescence staining was detected within nuclei of granulosa
      cells, together with positive stain for calretinin, confirming the presence of
      granulosa cell. Moreover, IL-2 gene expression was demonstrated in luteinized
      granulosa cells by real-time PCR. CONCLUSION: In the present study, we provided
      firm evidence for the IL-2 production by human luteinized granulosa cells, as
      demonstrated by the presence of IL-2 and IL-2 mRNA expression in luteinized
      granulosa cells. Further studies are justified in an attempt to clarify the
      regulation and the cause-and-effect relationship between IL-2 production by the
      hyperstimulated ovaries and OHSS.

PMID- 26219922
TI  - Inhibition of Cholesterol and Polyunsaturated Fatty Acids Oxidation through the
      Use of Annatto and Bixin in High-Pressure Processed Fish.
AB  - Annatto and bixin, the main carotenoid of annatto seeds, were both found to
      inhibit cholesterol oxidation in minced herring (Clupea harengus) and minced
      mackerel (Scomber scombrus) during high pressure processing (600 MPa for 10 min)
      and subsequent chilled storage for 2 wk, a treatment which otherwise increased
      the content of cholesterol oxidation products above a critical limit for human
      consumption. Annatto but not bixin reduced the loss of docosahexaenoic acid
      caused by high pressure processing of herring from 12% to 7%, an effect assigned
      to antioxidative effects of phenolic compounds in annatto, while bixin as a
      carotenoid binds to membranes protecting membrane cholesterol. 

PMID- 26219923
TI  - Effects of prospective thinking on intertemporal choice: The role of familiarity.
AB  - Imagining future events while performing an intertemporal choice task can
      attenuate the devaluation of future rewards. Here, we investigated whether this
      effect and its neural basis depend on the degree of personal prior experience
      associated with the simulated future scenarios. Functional magnetic resonance
      imaging was combined with a modified intertemporal choice task in which the
      delayed options were either purely monetary, or linked with a social event.
      Subject-specific events differed regarding familiarity, that is, meeting a close,
      familiar person or a celebrity in a cafe. In line with recent hypotheses on
      episodic construction, the simulation of future familiar and unfamiliar events
      equally attenuated delay discounting behavior in comparison with the control
      condition and both were imagined with similar richness. Imaging data, however,
      indicate that these results rely on differential neural activation patterns. The
      hippocampus was particularly involved in the simulation of unfamiliar future
      scenarios, probably reflecting enhanced construction processes when personal
      experience with similar past events is lacking. Consequently, functional coupling
      of the hippocampus with neural valuation signals in the anterior cingulate cortex
      predicted the subjective value only of rewards offered in the unfamiliar context.
      In contrast, valuation of rewards in a familiar context was predicted by
      activation in key nodes of emotional and autobiographical memory retrieval and
      dynamically modulated by frontal-striatal connectivity. The present data
      emphasize that the mechanisms underlying neural valuation of prospective rewards
      largely depend on the pre-experience with the context in which they are offered.

PMID- 26219924
TI  - Canaries in the coal mine: Personal and professional impact of undergoing whole
      genome sequencing on medical professionals.
AB  - Public interest in personal whole genome sequencing is increasing. The technology
      is publicly available and is being used as an educational tool in higher
      education. Empirical evidence regarding its utility is vital. The goals of this
      study were to characterize the process of whole genome sequencing in a population
      of medical and basic science professionals undergoing whole genome sequencing as
      a part of an educational symposium. Thirty-eight individuals completed one or
      more surveys from the time of informed consent for whole genome sequencing to 3
      months post-symposium. The four surveys assessed demographics, decision-making,
      communication, decision regret, and personal and professional impact. The most
      prevalent motivation to participate was professional enhancement, followed by
      curiosity about the technology, and personal health benefits. The most important
      initial impact concerned medical implications. Over time, however, impact on
      professional development was greater than on personal health. Anticipated
      reactions to receiving whole genome sequencing results generally matched
      participants' actual reactions and decision regret remained low over time.
      Benefits and risks of whole genome sequencing included medically actionable
      results and misunderstanding by healthcare providers. Whole genome sequencing
      generally had a positive impact professionally and personally on participants.
      Further education of providers and the public about whole genome sequencing and
      psychosocial support is warranted.

PMID- 26219925
TI  - An Oxofluoride Catalyst Comprised of Transition Metals and a Metalloid for
      Application in Water Oxidation.
AB  - The application of the recently discovered oxofluoride solid solution (Cox Ni1-x
      )3 Sb4 O6 F6 as a catalyst for water oxidation is demonstrated. The phase
      exhibits a cubic arrangement of the active metal that forms oxo bridges to the
      metalloid with possible catalytic participation. The Co3 Sb4 O6 F6 compound
      proved to be capable of catalyzing 2H2 O->O2 +4H(+) +4e(-) at 0.33 V
      electrochemical and <=0.39 V chemical overpotential with a TOF of 4.4?10(-3) ,
      whereas Ni3 Sb4 O6 F6 needs a higher overpotential. Relatively large crystal
      cubes (0.3-0.5 mm) are easily synthesized and readily handled as they demonstrate
      both chemical resistance to wear after repeated in situ tests under experimental
      conditions, and have a mechanical hardness of 270 V0.1 using Vickers indentation.
      The combined properties of this compound offer a potential technical advantage
      for incorporation to a catalytic interface in future sustainable fuel production.

PMID- 26219926
TI  - The hexacyanodiborane(6) dianion [B2(CN)6](2-).
AB  - Diborane(6) dianions with substituents that are bonded to boron via carbon are
      very reactive and therefore only a few examples are known. Diborane(6)
      derivatives are the simplest catenated boron compounds with an electron-precise B
      B sigma-bond that are of fundamental interest and of relevance for material
      applications. The homoleptic hexacyanodiborane(6) dianion [B2 (CN)6 ](2-) that is
      chemically very robust is reported. The dianion is air-stable and resistant
      against boiling water and anhydrous hydrogen fluoride. Its salts are thermally
      highly stable, for example, decomposition of (H3 O)2 [B2 (CN)6 ] starts at 200 
      degrees C. The [B2 (CN)6 ](2-) dianion is readily accessible starting from 1)
      B(CN)3 (2-) and an oxidant, 2) [BF(CN)3 ](-) and a reductant, or 3) by the
      reaction of B(CN)3 (2-) with [BHal(CN)3 ](-) (Hal=F, Br). The latter reaction was
      found to proceed via a triply negatively charged transition state according to an
      SN 2 mechanism. 

PMID- 26219927
TI  - Oxygen vacancies and intense luminescence in manganese loaded Zno microflowers
      for visible light water splitting.
AB  - ZnO nanorods and Mn/ZnO microflowers with nano-sized petals exhibit singly
      ionized oxygen vacancies, V. This is strongly supported by a green
      photoluminescence emission at 2.22 eV and an EPR g value of 1.953, both of which
      are suppressed greatly after annealing in an oxygen atmosphere. A strong red
      emission observed during exposure to X-rays reveals the presence of F(+) centres
      as a consequence of the V. Mn/ZnO displayed enhanced H2 generation with visible
      light exposure, when compared to pure ZnO and annealed Mn/ZnO in the visible
      region, which directly correlated with the oxygen vacancy concentration. There is
      an interesting correlation between the intensities of the EPR lines at the g
      value of 1.953 due to the oxygen vacancies, the intensity of light emitted from
      the exposure to X-rays, the intensity of the photoluminescence due to oxygen
      vacancies and the quantity of H2 produced by the photocatalytic effect when
      comparing the three different nanomaterials, viz. pure ZnO, Mn/ZnO before and
      after annealing, all having been made exactly by the same methodologies. 

PMID- 26219928
TI  - A novel conception for spontaneous transversions caused by homo-pyrimidine DNA
      mismatches: a QM/QTAIM highlight.
AB  - We have firstly shown that the T.T(w) and C.C(w) DNA mismatches with wobble (w)
      geometry stay in slow tautomeric equilibrium with short T.T*(WC) and C.C*(WC)
      Watson-Crick (WC) mispairs. These non-dissociative tautomeric rearrangements are
      controlled by the plane-symmetric, highly stable, highly polar and zwitterionic
      transition states. The obtained results allow us to understand in what way the
      T.T(w) and C.C(w) mismatches acquire enzymatically competent T.T*(WC) and
      C.C*(WC) conformations directly in the hydrophobic recognition pocket of a high
      fidelity DNA-polymerase, thereby producing thermodynamically non-equilibrium
      spontaneous transversions. The simplest numerical estimation of the frequency
      ratio of the TT to CC spontaneous transversions satisfactorily agrees with
      experimental data. 

PMID- 26219929
TI  - Determination of the optical gap bowing parameter for ternary Ni1-xZnxO cubic
      rocksalt solid solutions.
AB  - The lattice parameter variation for phase pure cubic rocksalt (RS) Ni1-xZnxO
      ternary solid solutions is observed to be perfectly governed by Vegard's law. X
      ray absorption near edge spectroscopy confirms the RS symmetry of Zn atoms in the
      cubic lattice of Ni1-xZnxO. The optical gap bowing parameter for RS Ni1-xZnxO
      ternary solid solutions is determined, using diffuse reflectivity, to be -0.93 +/
      0.05 eV. The negative value of the bowing indicates a repulsive interaction
      between the ligand O-2p and the metal Ni-3d orbitals. The determined value of the
      bowing parameter can be useful in designing UV photodetectors based on Ni1-xZnxO
      solid solutions. 

PMID- 26219930
TI  - Identification of intranuclear inclusions is useful for the cytological diagnosis
      of ovarian clear cell carcinoma.
AB  - OBJECTIVE: The aim of this study was to clarify the diagnostic significance of
      the presence of intranuclear inclusions in clear cell carcinoma (CCC). MATERIALS
      AND METHODS: We analyzed 98 imprint specimens and 53 ascites specimens from 98
      ovarian carcinoma cases [28 CCCs, 37 serous carcinomas (SCs), 22 endometrioid
      carcinomas (ECs), and 11 mucinous carcinomas (MCs)]. We examined (1) frequency of
      intranuclear inclusion-positive cases of each ovarian carcinoma subtype, using
      imprint specimens, (2) frequency of intranuclear inclusion-positive cells of each
      ovarian carcinoma subtype, using imprint specimens, (3) frequency of intranuclear
      inclusion-positive cases of each ovarian carcinoma subtype, using ascites
      specimens, and (4) sensitivity and specificity of the presence of intranuclear
      inclusions for the cytological diagnosis of CCC. RESULTS: (1) The frequency of
      intranuclear inclusion-positive cases in CCC (96.4%) was significantly higher
      than in SC (13.5%), EC (13.6%), and MC (18.2%) (P < 0.001). Two or more
      intranuclear inclusions in a single nucleus were observed only in CCC. (2) The
      frequency of intranuclear inclusion-positive cells in CCC (median, 0.41%) was
      significantly higher than in non-CCC subtypes (0.010%) (P < 0.001). (3) Using
      ascites specimens, the frequency of intranuclear inclusion-positive cases in CCC
      (78.6%) was significantly higher than in SC (10.3%), EC (0%), and MC (0%) (P <
      0.001). (4) The sensitivity of intranuclear inclusions was 96.4%, and the
      specificity was 85.7%. CONCLUSIONS: The identification of intranuclear
      inclusions, in particular a high frequency and multiple intranuclear inclusions
      in a single nucleus, is useful for the cytological diagnosis of CCC. Furthermore,
      these results may be applicable to ascites cytology.

PMID- 26219931
TI  - Recent Patents in Pulmonary Delivery of Macromolecules.
AB  - Pulmonary delivery is a non-invasive form of delivery that holds tremendous
      therapeutic promise for topical and systemic administration of several
      macromolecules. Oral administration of macromolecules has several limitations
      such as low bioavailability, degradation of drug before reaching circulation and
      insufficient absorption across intestinal membrane. Administration of
      macromolecules such as proteins, peptides and nucleic acids via inhalation offers
      great potential due to the avoidance of first pass metabolism, higher surface
      area and rapid clinical response. However, delivery of reproducible, uniform and
      safe doses of inhaled particles remains a major challenge for clinical
      translation. Recent advances in the fields of biotechnology and particle
      engineering led to progress in novel pulmonary drug delivery systems. Moreover,
      significant developments in carriers and delivery devices prevent denaturation of
      macromolecules and control their release within the lungs. This article reviews
      the advances in pulmonary drug delivery systems by focusing on the recent patents
      in delivery of macromolecules. Furthermore, recent patents in gene delivery to
      the lungs have also been discussed. List of patents included in this review is
      comprehensive in terms of pulmonary delivery of therapeutics. It includes
      inventions related to proteins and peptides, DNA therapeutics, siRNA and other
      genetic materials with therapeutic applications. The diseases targeted by these
      therapeutic molecules are varied including but not limited to different forms of
      cancer, respiratory diseases etc. 

PMID- 26219932
TI  - Evaluation of the In Vitro Efficacy of Sevelamer Hydrochloride and Sevelamer
      Carbonate.
AB  - The objective of this project is to develop an in vitro approach that can be used
      to determine the phosphate binding capacity of sevelamer hydrochloride and
      carbonate for both drug products and active pharmaceutical ingredients (APIs). A
      simple and efficient inductively coupled plasma spectrometer method for analysis
      of phosphate at physiologically relevant pH conditions has been developed and
      validated. The method addresses each of the analytical validation characteristics
      such as linearity, accuracy, precision, stability, and selectivity, and meets the
      acceptance criteria defined in the United States Food and Drug Administration
      guidance (Food and Drug Administration, Center for Drug Evaluation and Research.
      2001. Guidance for industry-Bioanalytical method validation, May). The in vitro
      phosphate binding efficacies were systematically evaluated and compared for two
      drug products and two APIs. The phosphate binding profiles appeared similar
      between the drug products. Under all conditions, the sevelamer-phosphate binding
      reached equilibrium at 6 h. The 90% confidence interval for the k2 ratio
      (sevelamer carbonate vs. sevelamer hydrochloride) was well within 80%-125% under
      all pH conditions. However, the k1 ratio varied, indicating that there exists
      difference in the binding affinity. Our findings will be useful in assisting with
      "in vivo" biowaiver for the approval of generic sevelamer drug products.

PMID- 26219934
TI  - What is the optimal treatment for benign multinodular goitre?

PMID- 26219933
TI  - Retino-protective effect of Bucida buceras against oxidative stress induced by
      H2O2 in human retinal pigment epithelial cells line.
AB  - BACKGROUND: Reactive Oxygen Species (ROS) impair the physiological functions of
      Retinal Pigment Epithelial (RPE) cells, which are known as one major cause of age
      related macular degeneration and retinopathy diseases. The purpose of this study
      is to explore the cytoprotective effects of the antioxidant Bucida buceras
      extract in co-treatment with hydrogen peroxide (H2O2) delivery as a single
      addition or with continuous generation using glucose oxidase (GOx) in ARPE-19
      cell cultures. The mechanism of Bucida buceras extract is believed to be
      associated with their antioxidant capacity to protect cells against oxidative
      stress. METHODS: A comparative oxidative stress H2O2-induced was performed by
      addition and enzymatic generation using glucose oxidase on human retinal pigment
      epithelial cells line. H2O2-induced injury was measured by toxic effects (cell
      death and apoptotic pathway) and intracellular redox status: glutathione (GSH),
      antioxidant enzymes (catalase and glutathione peroxidase) and reducing power
      (FRAP). The retino-protective effect of co-treatment with Bucida buceras extract
      on H2O2-induced human RPE cell injury was investigated by cell death (MTT assay)
      and oxidative stress biomarkers (H2O2, GSH, CAT, GPx and FRAP). RESULTS: Bucida
      buceras L. extract is believed to be associated with the ability to prevent
      cellular oxidative stress. When added as a pulse, H2O2 is rapidly depleted and
      the cytotoxicity analyses show that cells can tolerate short exposure to high
      peroxide doses delivered as a pulse but are susceptible to lower chronic doses.
      Co-treatment with Bucida buceras was able to protect the cells against H2O2
      induced injury. In addition to preventing cell death treatment with antioxidant
      plant could also reverse the significant decrease in GSH level, catalase activity
      and reducing power caused by H2O2. CONCLUSION: These findings suggest that Bucida
      buceras could protect RPE against ocular pathogenesis associated with oxidative
      stress induced by H2O2-delivered by addition and enzymatic generation.

PMID- 26219935
TI  - Late-onset inflammatory bowel disease in the very elderly.
AB  - Elderly-onset inflammatory bowel disease (IBD) will be seen more frequently with
      the ageing of the population and the increasing incidence of IBD. However,
      knowledge regarding the best approach to IBD in this population is scarce.
      Furthermore, differential diagnosis in elderly patients with diarrhoea, rectal
      blood loss or a changed defecation pattern is comprehensive and IBD is not always
      considered. In this case series, we present three elderly patients with late
      onset IBD, demonstrating the difficulties in diagnosing and treating IBD in this
      patient population; in addition an overview of IBD in the elderly is provided. 

PMID- 26219936
TI  - Susac syndrome: a report of four cases and a review of the literature.
AB  - In Susac syndrome, occlusions of pre-capillary arterioles of the brain, retina,
      and cochlea lead to the classical clinical triad of subacute encephalopathy,
      visual disturbances due to branch retinal artery occlusions and sensorineural
      hearing impairment. Its pathogenesis is still obscure, but it is presumed to be
      mediated by an autoimmune response to an as yet unknown antigen. The syndrome is
      considered a rare but important differential diagnosis in various neurological,
      psychiatric, ophthalmological, and ear-nose-throat disorders. Brain magnetic
      resonance imaging, retinal fluorescein angiography, and audiometry findings
      enable diagnosis. Early therapy may reduce relapses and improve recovery. The
      features of four cases of this syndrome are presented, illustrating that
      cooperation among different medical specialists is essential, and that treatment
      may be best guided by an immunologist or rheumatologist as a case manager. 

PMID- 26219937
TI  - Is hemithyroidectomy a rational management for benign nodular goitre? A
      Multicentre Retrospective Single Group Study.
AB  - BACKGROUND: The incidence and potential risk factors for the recurrence of benign
      nodular goitre after unilateral thyroidectomy are not clearly defined. The aim of
      this study was to assess the rate of progression of nodular goitre in the
      contralateral thyroid lobe and of hypothyroidism requiring replacement therapy
      after unilateral thyroid lobectomy for benign nodular goitre. PATIENTS AND
      METHODS: Patients who underwent hemithyroidectomy for benign nodular goitre
      between 2000 and 2009 were included in the study. The primary outcome of this
      study was the reoperation rate for recurrent goitre, the rate of progression of
      nodular goitre and the rate of hypothyroidism requiring L-T4 replacement therapy.
      Clinical factors that have an effect on progression were further analysed.
      RESULTS: 259 patients were included for study. Progression of the nodular goitre
      in the remnant lobe was observed in 32% (n = 83) of the patients. However, over
      time, only 2% of these 83 patients underwent contralateral hemithyroidectomy due
      to this progression. Fifty-six (22%) patients required L-thyroxin replacement due
      to persistent hypothyroidism after hemithyroidectomy. The factors shown to affect
      progression of nodular goitre were advanced age, preoperative hyperthyroidism,
      preoperative diagnosis of toxic nodular goitre and the presence of surgical
      indication for a toxic goitre causing hyperthyroidism and a definitive
      pathological diagnosis of nodular hyperplasia. CONCLUSION: There was a
      progression of the nodular goitre in the remnant lobe in about one-third of the
      patients who underwent hemithyroidectomy. However, only 2% of these patients
      underwent complementary contralateral hemithyroidectomy due to clinical
      progression in 31 months of follow-up.

PMID- 26219938
TI  - Thromboprophylaxis for lower leg cast immobilisation and knee arthroscopy: a
      survey study.
AB  - BACKGROUND: The effect of prophylaxis on the prevention of symptomatic venous
      thrombosis in patients with lower leg cast immobilisation or after knee
      arthroscopy is not clear. Our aim was to assess the current practice of
      thrombosis prophylaxis in Dutch hospitals and to determine considerations for
      prescribing prophylaxis. METHODS: Electronic questionnaires regarding thrombosis
      prophylaxis in patients with lower leg cast immobilisation or after knee
      arthroscopy were sent to all orthopaedic (90) and trauma surgery departments (89)
      and orthopaedic clinics (16) in the Netherlands. RESULTS: Response rate was 88%
      for orthopaedic surgery departments/clinics and 81% for trauma surgery
      departments. Analysis of the questionnaires reveals that prophylaxis was not
      provided for patients with lower leg cast immobilisation at only 3 (4%)
      orthopaedic and 3 (4%) trauma surgery departments, while 10 (11%) orthopaedic
      surgery departments did not provide prophylaxis for patients undergoing knee
      arthroscopies. Substantial differences in prophylactic strategies were observed
      as these strategies were dependent on both the indication for treatment and on
      the presence of concomitant risk factors for venous thrombosis. The most reported
      rationales for prescribing prophylaxis were: the perceived risk reduction of
      prophylaxis outweighs the bleeding risk; the experience that prophylaxis is
      effective; to act in accordance with hospital guidelines. CONCLUSION: Despite the
      lack of a solid evidence base, it seems that the large majority of patients with
      lower leg cast immobilisations, along with those undergoing knee arthroscopy, do
      receive thrombosis prophylaxis. However, depending on the indications, large
      variations within prophylaxis strategies seem to exist, which demonstrate the
      need for an evidence-based uniform prophylaxis scheme.

PMID- 26219939
TI  - Dysphagia, malnutrition and gastrointestinal problems in patients with
      mitochondrial disease caused by the m3243A>G mutation.
AB  - BACKGROUND: Previous research has shown that dysphagia and gastrointestinal
      problems occur frequently in carriers of the m.3243A>G mutation; however, the
      exact frequency and severity have not been determined. We hypothesise that adult
      carriers have an increased risk for malnutrition. METHODS: In this observational
      study we evaluated the presence of gastrointestinal problems and dysphagia in 92
      carriers of the m.3243A>G mutation. The severity of the general disease
      involvement was classified using the Newcastle Mitochondrial Disease Adult Scale
      (NMDAS). Gastrointestinal involvement, dysphagia and the risk for malnutrition
      were scored using the Gastrointestinal Symptoms Questionnaire and the
      Malnutrition Universal Screening Tool. Gastrointestinal symptoms and
      anthropometrics were compared with healthy controls. RESULTS: Our results show
      that the height, weight and body mass index (BMI) of these carriers were lower
      than the national average (p < 0.05). Seventy-nine carriers (86%) suffered from
      at least one gastrointestinal symptom, mainly flatulence or hard stools. Both
      frequency and severity of symptoms were significantly increased compared with
      reference data of healthy Dutch adults. Of the carriers, 45% reported (mostly
      mild) dysphagia. Solid foods cause more problems than liquids. A negative
      correlation between BMI and heteroplasmy levels in urinary epithelial cells (UEC)
      was present (Spearman correlation coefficient = - 0.319, p = 0.003). CONCLUSION:
      Dysphagia and gastrointestinal problems, especially constipation, are common
      symptoms in the total m.3243A>G carriers cohort and are not related to
      heteroplasmy levels in UEC or disease severity. The severity of gastrointestinal
      problems as well as overall disease severity is associated with an increased risk
      for malnutrition.

PMID- 26219940
TI  - Cutaneous hyperpigmentation induced by doxycycline: a case series.
AB  - Cutaneous hyperpigmentation is a well-known side effect of tetracyclines, but
      doxycycline-induced cutaneous hyperpigmentation has only been described in one
      patient with a therapeutic dosage of doxycycline, and in one patient using
      suprapharmacological doses. We describe four patients with cutaneous
      hyperpigmentation in previously unaffected skin, and speculate that this was due
      to treatment with doxycycline in therapeutic doses. After cessation of therapy,
      the hyperpigmentation diminished in all four patients, illustrating the need for
      recognition and timely cessation of therapy. 

PMID- 26219941
TI  - Generalised peliosis hepatis mimicking metastases after long-term use of oral
      contraceptives.
AB  - Peliosis hepatis (PH) is a rare vascular condition of the liver characterised by
      the presence of cystic blood-filled cavities distributed randomly throughout the
      liver parenchyma. PH should be considered in the differential diagnosis of women
      with a long history of use of oral contraceptives with suspected hypervascular
      lesions diagnosed by imaging, but with an unknown primary tumour. Because of the
      extensive use of oral contraceptives in the general female population worldwide,
      PH should be added to the differential diagnosis of suspected hypervascular liver
      lesions. 

PMID- 26219942
TI  - Cutaneous ulcer after a stay in the tropics.

PMID- 26219943
TI  - Are the current guidelines on contrast-induced nephropathy prevention
      superfluous?

PMID- 26219944
TI  - Unintentional nutmeg autointoxication.
AB  - Nutmeg ingestion in large amounts can cause toxic symptoms such as
      hallucinations, tachycardia and anticholinergic effects. We describe a case of a
      37-year-old woman who experienced an unintentional autointoxication of nutmeg. It
      is likely that nutmeg intoxication is underreported. We suggest to specifically
      think of nutmeg ingestion in case of symptoms as mentioned above. 

PMID- 26219945
TI  - Interaction preferences between nucleobase mimetics and amino acids in aqueous
      solutions.
AB  - Despite the paramount importance of protein-nucleic acid interactions in
      different cellular processes, our understanding of such interactions at the
      atomistic level remains incomplete. We have used molecular dynamics (MD)
      simulations and 15 MUs of sampling time to study the behavior of amino acids and
      amino-acid sidechain analogs in aqueous solutions of different mimetics of
      naturally occurring nucleobases, including dimethylpyridine (DMP) and
      unsubstituted purine and pyrimidine rings. By using structural and energetic
      analysis, we have derived preference scales for the interaction of amino acids
      and their sidechain analogs with different nucleobase mimetics and have
      exhaustively compared them with each other. A close correspondence with a
      standard hydrophobicity measure in the case of the pyrimidine mimetic DMP and
      purines suggests that the hydrophobic effect is the main defining factor behind
      such interactions. We analyze our findings in the context of the origin of the
      genetic code and the recently proposed cognate mRNA-protein complementarity
      hypothesis. Most importantly, we show that unsubstituted purine and pyrimidine
      rings alone cannot differentiate between predominantly purine- and pyrimidine
      coded amino acids, suggesting that for such specificity to exist, it must
      primarily reside in ring substituents. 

PMID- 26219946
TI  - Winogradskyella litoriviva sp. nov., isolated from coastal seawater.
AB  - A Gram-stain-negative, facultatively anaerobic, moderately halophilic and gliding
      bacterium, designated KMM 6491T, was isolated from coastal seawater collected
      from Troitsa Bay, the Sea of Japan. Comparative analysis of 16S rRNA gene
      sequences revealed that strain KMM 6491T was a member of the genus
      Winogradskyella, with 94.5-97.9 % sequence similarity to recognized species of
      the genus Winogradskyella. The DNA G+C content of strain KMM 6491T was 31.3 mol%
      and DNA-DNA relatedness values with the type strains of Winogradskyella
      echinorum, Winogradskyella damuponensis, Winogradskyella eximia and
      Winogradskyella pulchriflava were in range of 10-26 %. Strain KMM 6491T contained
      menaquinone 6 (MK-6) as the single quinone and iso-C15 : 0, iso-C15 : 1, iso-C15
      : 0 3-OH, iso-C17 : 0 3-OH, C15 : 0 and summed feature 3 (comprising iso-C15 : 0
      2-OH and/or C16 : 1omega7c) anteiso-C15 : 0, as the prevalent fatty acids. The
      major polar lipids of strain KMM 6491T were phosphatidylethanolamine, two unknown
      aminolipids and two unknown lipids. Strain KMM 6491T was able to grow with 0.5-7
      % NaCl and at 4-34  degrees C. The novel strain decomposed gelatin and starch and
      produced acid from d-glucose, maltose, mannose, rhamnose, sucrose, fructose and
      glycerol. On the basis of the results of the phylogenetic and phenotypic analyses
      it is suggested that strain KMM 6491T represents a novel species of the genus
      Winogradskyella, for which the name Winogradskyella litoriviva sp. nov. is
      proposed. The type strain is KMM 6491T ( = KCTC 23972T = LMG 26984T).

PMID- 26219947
TI  - Discovery of a novel putative atypical porcine pestivirus in pigs in the USA.
AB  - Pestiviruses are some of the most significant pathogens affecting ruminants and
      swine. Here, we assembled a 11 276 bp contig encoding a predicted 3635 aa
      polyprotein from porcine serum with 68 % pairwise identity to that of a recently
      partially characterized Rhinolophus affinis pestivirus (RaPV) and approximately
      25-28 % pairwise identity to those of other pestiviruses. The virus was
      provisionally named atypical porcine pestivirus (APPV). Metagenomic sequencing of
      182 serum samples identified four additional APPV-positive samples. Positive
      samples originated from five states and ELISAs using recombinant APPV Erns found
      cross-reactive antibodies in 94 % of a collection of porcine serum samples,
      suggesting widespread distribution of APPV in the US swine herd. The molecular
      and serological results suggest that APPV is a novel, highly divergent porcine
      pestivirus widely distributed in US pigs.

PMID- 26219948
TI  - Evaluation of cefazolin as a surrogate marker for cefpodoxime susceptibility for
      urinary tract isolates.
AB  - Of the cephalosporins, cefpodoxime has the most published clinical data for the
      treatment of urinary tract infections. In 2014, the Clinical and Laboratory
      Standards Institute (CLSI) guidelines recommended that cefazolin should be used
      as the surrogate marker for cefpodoxime among urinary tract isolates, replacing
      cephalothin. This study attempted to determine how well cefazolin serves as the
      surrogate marker. Additionally, it investigated how cefuroxime compared with
      cefazolin as a surrogate marker. The MicroScan Walkaway Plus system was used to
      determine susceptibility for cefazolin and cefuroxime on consecutive urine
      cultures with a colony count of >= 50 000 organisms. Only Escherichia coli,
      Klebsiella pneumoniae and Proteus mirabilis isolates were included, following
      CLSI guidelines. Simultaneously, an Etest for cefpodoxime was conducted. The
      cefpodoxime interpretation was compared with that of the other two agents, and
      the categorical agreement was calculated, defined as the percentage of identical
      susceptibility interpretations. Cefazolin (92 %) had a significantly higher
      categorical agreement than cefuroxime (85 %) among 284 isolates (P = 0.011). The
      major error rate was 4.4 % for cefazolin and 1.1 % for cefuroxime. The very major
      error rate was 64 % for cefazolin and 18 % for cefuroxime among the 11
      cefpodoxime-resistant isolates. Cefazolin was a better predictor of cefpodoxime
      susceptibility than the previously recommended agent, cephalothin. However,
      cefuroxime had better major and very major error rates than cefazolin. 

PMID- 26219950
TI  - The equine forelimb suspensory ligament exhibits a heterogeneous strain pattern
      under tensile load.
AB  - OBJECTIVES: To determine if regional variations in strain patterns occur within
      the suspensory ligament under tensile load. Local increases in strain may put
      certain regions of the suspensory ligament at risk and may explain the poor
      healing and high recurrence rates associated with suspensory branch injuries.
      METHODS: The suspensory ligament and its bone attachments were isolated from each
      of 10 adult equine cadaveric forelimbs and radiodense reference beads were
      inserted throughout the length of the ligament. Specimens were attached to a
      custom fixture secured to a materials testing system. Radiographs were acquired
      at 50, 445, 1112, and 2224 N of applied tensile load. Changes in distances
      between the beads in each region of the suspensory ligament were measured and the
      regional strain was calculated. Significant differences were determined using a
      repeated-measures analysis of variance. RESULTS: The suspensory ligament
      exhibited significant differences in regional strain (p <0.001). The distal
      branches of the suspensory ligament had significantly greater strains than the
      proximal (p = 0.025) and mid-body (p = 0.002) regions. The mid-body of the
      suspensory ligament also exhibited local strain variation, with the distal mid
      body having significantly higher strains than the proximal mid-body (p = 0.038).
      CLINICAL SIGNIFICANCE: The equine suspensory ligament demonstrates a
      heterogeneous strain pattern during tensile loading, with the distal regions
      exhibiting significantly more strain than the proximal region. The non-homogenous
      strain pattern could explain the regional difference in injury and re-injury
      rates.

PMID- 26219951
TI  - Ochratoxin A in dried grapes in Hamadan province, Iran.
AB  - The occurrence of ochratoxin A (OTA) in dried grapes was surveyed in this study.
      Sixty-six samples of dried grapes (40 currants, 16 sultanas and 10 raisins) were
      collected from dried grapes factories in Hamadan province, Iran, from October
      2012 to March 2013. High-performance liquid chromatography (HPLC) was used to
      determine OTA in these samples. OTA was detected in 23 (57.5%) currants, 10
      (62.5%) sultanas and 6 (60%) raisins samples. Levels in five samples exceeded the
      Institute of Standards and Industrial Research of Iran (ISIRI) maximum level of 5
      ug/kg. However, OTA content in none of the samples exceeded the maximum limit
      prescribed in the European Union (EU) regulations, which is 10 ug/kg. The
      obtained data contribute to information on OTA levels in Iranian dried grapes. 

PMID- 26219949
TI  - Making inroads into improving treatment of bacterial vaginosis - striving for
      long-term cure.
AB  - Bacterial vaginosis (BV) is one of the great enigmas in women's health, a common
      condition of unknown aetiology, which is associated with significant morbidity
      and unacceptably high recurrence rates. While it remains unclear whether BV
      recurrence is predominantly due to failure of current antibiotic regimens to
      eradicate BV-associated bacteria (BVAB) and biofilm, a failure of some women to
      re-establish a resilient Lactobacillus-dominant vaginal microbiota, reinfection
      from sexual partners, or a combination of these factors, it is inherently
      challenging to make significant inroads towards this goal. In this review, we
      will outline why BV is such a clinical and epidemiologic conundrum, and focus on
      several key approaches that we believe merit discussion and clinical research,
      including strategies to: i) prevent reinfection (partner treatment trials), ii)
      boost favourable vaginal Lactobacillus species and promote a Lactobacillus
      dominant vaginal microbiome (hormonal contraceptive and probiotic trials) and
      iii) disrupt vaginal BV-associated biofilm. 

PMID- 26219952
TI  - Inhibition of NOX1/4 with GKT137831: a potential novel treatment to attenuate
      neuroglial cell inflammation in the retina.
AB  - BACKGROUND: Inflammation and the excess production of reactive oxygen species
      (ROS) contribute significantly to the pathogenesis of ischemic retinopathies such
      as diabetic retinopathy and retinopathy of prematurity. We hypothesized that
      GKT137831, a dual inhibitor of NADPH oxidases (NOX) 1 and NOX4, reduces
      inflammation in the ischemic retina by dampening the pro-inflammatory phenotype
      of retinal immune cells as well as macroglial Muller cells and neurons. METHODS:
      Ischemic retinopathy was induced in Sprague-Dawley rats by exposure to 80 % O2
      cycled with 21 % O2 for 3 h per day from postnatal day (P) 0 to P11, followed by
      room air (P12 to P18). GKT137831 was administered P12 to P18 (60 mg/kg,
      subcutaneous) and comparisons were to room air controls. Retinal inflammation was
      examined by measuring leukocyte adherence to the retinal vasculature, ionized
      calcium-binding adaptor protein-1-positive microglia/macrophages, and the mRNA
      and protein levels of key inflammatory factors involved in retinal disease.
      Damage to Muller cells was evaluated by quantitating glial fibrillary acidic
      protein-positive cells and vascular leakage with an albumin ELISA. To verify the
      anti-inflammatory actions of GKT137831 on glia and neurons involved in ischemic
      retinopathy, primary cultures of rat retinal microglia, Muller cells, and
      ganglion cells were exposed to the in vitro counterpart of ischemia, hypoxia (0.5
      %), and treated with GKT137831 for up to 72 h. ROS levels were evaluated with
      dihydroethidium and the protein and gene expression of inflammatory factors with
      quantitative PCR, ELISA, and a protein cytokine array. RESULTS: In the ischemic
      retina, GKT137831 reduced the increased leukocyte adherence to the vasculature,
      the pro-inflammatory phenotype of microglia and macroglia, the increased gene and
      protein expression of vascular endothelial growth factor, monocyte
      chemoattractant protein-1, and leukocyte adhesion molecules as well as vascular
      leakage. In all cultured cell types, GKT137831 reduced the hypoxia-induced
      increase in ROS levels and protein expression of various inflammatory mediators.
      CONCLUSIONS: NOX1/4 enzyme inhibition with GKT137831 has potent anti-inflammatory
      effects in the retina, indicating its potential as a treatment for a variety of
      vision-threatening retinopathies.

PMID- 26219953
TI  - Dynamic regulation of the proteasome by systolic overload.

PMID- 26219954
TI  - Proarrhythmic effect of sustained EPAC activation on TRPC3/4 in rat ventricular
      cardiomyocytes.
AB  - The Exchange Protein directly Activated by cAMP (EPAC) participates to the
      pathological signaling of cardiac hypertrophy and heart failure, in which the
      role of Ca(2+) entry through the Transient Receptor Potential Canonical (TRPC)
      channels begin to be appreciated. Here we studied whether EPAC activation could
      influence the activity and/or expression of TRPC channels in cardiac myocytes. In
      adult rat ventricular myocytes treated for 4 to 6h with the selective EPAC
      activator, 8-pCPT (10MUM), we observed by Fluo-3 confocal fluorescence a Store
      Operated Ca(2+) Entry (SOCE) like-activity, which was blunted by co-incubation
      with EPAC inhibitors (ESI-05 and CE3F4 at 10 MUM). This SOCE-like activity, which
      was very small in control incubated cells, was sensitive to 30-MUM SKF-96365.
      Molecular screening showed a specific upregulation of TRPC3 and C4 protein
      isoforms after 8-pCPT treatment. Moreover, sustained EPAC activation favored
      proarrhythmic Ca(2+) waves, which were reduced either by co-incubation with EPAC
      inhibitors or bath perfusion with TRPC inhibitors. Our study provides the first
      evidence that sustained selective EPAC activation leads to an increase in TRPC3
      and C4 protein expression and induces a proarrhythmic SOCE-like activity in adult
      rat ventricular cardiomyocytes, which might be of importance during the
      development of cardiac diseases.

PMID- 26219955
TI  - Health care utilization in older people with cardiovascular disease in China.
AB  - BACKGROUND: Population is ageing rapidly and prevalence of cardiovascular
      diseases is increasing in China. This study aims to examine the patterns of
      outpatient and inpatient health care utilization across different demographic and
      socioeconomic groups in older people with cardiovascular disease in China.
      METHODS: Data were from World Health Organization (WHO) Study on Global Aging and
      Adult Health (SAGE) Wave 1. Chinese older people aged over 50 years with
      cardiovascular disease were included in the analysis. Outpatient and inpatient
      care utilization rates were presented and compared by demographic and
      socioeconomic characteristics. Multivariable logistic regression was used to
      examine the association between socioeconomic factors and health care
      utilization. RESULTS: In total, 4162 older people with cardiovascular disease in
      SAGE China Wave 1 were included in the analysis. 86.4% of them had health
      insurance. 54.9% of the patients received outpatient care and 17.7% received
      inpatient care over the past 12 months. Outpatient care utilization rate was
      significantly associated with age. Patients in older groups used more outpatient
      care than those in younger groups (p = 0.010). Inpatient care utilization rate
      peaked at 70-79 years group (23.2%), and then reduced to 17.5% in 80 years plus
      group. Rich patients used more outpatient service than the poorer (p < 0.001). No
      association was found between household wealth status and inpatient service
      utilization. CONCLUSION: Within the context of high health insurance coverage in
      China, the pattern of outpatient care utilization differs from that of inpatient
      care utilization among older patients aged over 50 years old with cardiovascular
      disease. Patients tend to use more outpatient care as they became older. As for
      inpatient care, the oldest patients aged over 80 years use less inpatient care
      than the 70-79 group. Household economic status plays an important role in
      outpatient care utilization, but it shows no association with inpatient care
      utilization in Chinese older patients.

PMID- 26219956
TI  - Limitations of three-dimensional power Doppler angiography in preoperative
      evaluation of ovarian tumors.
AB  - BACKGROUND: This study describes the accuracy of three-dimensional power Doppler
      (3D-PD) angiography as secondary method for differential diagnosis of ovarian
      tumors. METHOD: Seventy-five women scheduled for surgical removal of adnexal
      masses were assessed by transvaginal ultrasound. Ovarian tumors were classified
      by IOTA simple rules and two three-dimensional blocks were recorded. In a second
      step analyses, a 4 cm(3) spherical sample was obtained from the highest
      vascularized solid area of each stored block. Vascularization index (VI), flow
      index (FI) and vascularization-flow index (VFI) were calculated. The
      repeatability was assessed by concordance correlation coefficient (CCC) and
      limits of agreement (LoA), and diagnostic accuracy by area under ROC curve.
      RESULTS: IOTA simple rules classified 26 cases as benign, nine as inconclusive
      and 40 as malignant. There were eight false positive and no false negative. Among
      the masses classified as inconclusive or malignant by IOTA simple rules, the CCCs
      were 0.91 for VI, 0.70 for FI, and 0.86 for VFI. The areas under ROC curve were
      0.82 for VI, 0.67 for FI and 0.81 for VFI. CONCLUSIONS: 3D-PD angiography
      presented considerable intraobserver variability and low accuracy for identifying
      false positive results of IOTA simple rules.

PMID- 26219957
TI  - Volumetric and dosimetric changes to salivary glands during radiotherapy for head
      and neck cancer.

PMID- 26219958
TI  - Weekly kilovoltage cone-beam computed tomography for detection of dose
      discrepancies during (chemo)radiotherapy for head and neck cancer.
AB  - BACKGROUND: Use of highly conformal radiotherapy in patients with head and neck
      carcinoma may lead to under-/overdosage of gross target volume (GTV) and organs
      at risk (OAR) due to changes in patients' anatomy. A method to achieve more
      effective radiation treatment combined with less toxicity is dose-guided
      radiotherapy (DGRT). The aim of this study was to evaluate discrepancies between
      planned and actually delivered radiation dose in head and neck patients and to
      identify predictive factors. METHODS: In this retrospective analysis, 20 patients
      with cT2-4 N0-3 M0 carcinoma originating from oropharynx, oral cavity, larynx and
      hypopharynx (Cohort 1), and seven patients with cT1-4 N0-3 M0 nasopharyngeal
      carcinoma (Cohort 2) treated with primary (chemo)radiotherapy and undergoing
      weekly kV-CBCT scans were included. Radiation dose was recalculated on 184 kV
      CBCT images, which was quantified by D95% (GTV), Dmean (parotid and submandibular
      glands) and D2% (spinal cord). Predictive factors investigated for changes in
      these dose metrics were: gender, age, cT/N-stage, tumor grade, HPV-status,
      systemic therapy, body mass index at start of treatment, weight loss and volume
      change over the duration of the radiotherapy. RESULTS: There was no significant
      difference between the planned and delivered dose for GTV and OARs of Week 1 to
      subsequent weeks for Cohort 1. In Cohort 2, actually delivered Dmean to parotid
      glands was significant higher than planned dose (1.1 Gy, p = 0.002). No
      clinically relevant correlations between dose changes and predictive factors were
      found. CONCLUSION: Weekly dose calculations do not seem to improve dose delivery
      for patients with tumors of the oral cavity, oropharynx, larynx and hypopharynx.
      In patients with nasopharyngeal carcinoma, however, mid-treatment imaging may
      facilitate DGRT.

PMID- 26219959
TI  - A simulation study on proton computed tomography (CT) stopping power accuracy
      using dual energy CT scans as benchmark.
AB  - BACKGROUND: Accurate stopping power estimation is crucial for treatment planning
      in proton therapy, and the uncertainties in stopping power are currently the
      largest contributor to the employed dose margins. Dual energy x-ray computed
      tomography (CT) (clinically available) and proton CT (in development) have both
      been proposed as methods for obtaining patient stopping power maps. The purpose
      of this work was to assess the accuracy of proton CT using dual energy CT scans
      of phantoms to establish reference accuracy levels. MATERIAL AND METHODS: A CT
      calibration phantom and an abdomen cross section phantom containing inserts were
      scanned with dual energy and single energy CT with a state-of-the-art dual energy
      CT scanner. Proton CT scans were simulated using Monte Carlo methods. The
      simulations followed the setup used in current prototype proton CT scanners and
      included realistic modeling of detectors and the corresponding noise
      characteristics. Stopping power maps were calculated for all three scans, and
      compared with the ground truth stopping power from the phantoms. RESULTS: Proton
      CT gave slightly better stopping power estimates than the dual energy CT method,
      with root mean square errors of 0.2% and 0.5% (for each phantom) compared to 0.5%
      and 0.9%. Single energy CT root mean square errors were 2.7% and 1.6%. Maximal
      errors for proton, dual energy and single energy CT were 0.51%, 1.7% and 7.4%,
      respectively. CONCLUSION: Better stopping power estimates could significantly
      reduce the range errors in proton therapy, but requires a large improvement in
      current methods which may be achievable with proton CT.

PMID- 26219960
TI  - Deep sequencing-based characterization of transcriptome of trifoliate orange
      (Poncirus trifoliata (L.) Raf.) in response to cold stress.
AB  - BACKGROUND: Trifoliate orange (Poncirus trifoliata (L.) Raf.) is extremely cold
      hardy after a full acclimation; however the underlying molecular mechanisms
      underlying this economically valuable trait remain poorly understood. In this
      study, global transcriptome profiles of trifoliate orange under cold conditions
      (4  degrees C) over a time course were generated by high-throughput sequencing.
      RESULTS: More than 68 million high-quality reads were produced and assembled into
      a non-redundant data of 77,292 unigenes with an average length of 1112 bp (N50 =
      1778 bp). Of these, 23,846 had significant sequence similarity to known genes and
      these were assigned to 61 gene ontology (GO) categories and 25 clusters of
      orthologous groups (COG) involved in 128 KEGG pathways. Sequences derived from
      cold-treated and control plants were mapped to the assembled transcriptome,
      resulting in the identification of 5549 differentially expressed genes (DEGs).
      These comprised 600 (462 up-regulated, 138 down-regulated), 2346 (1631 up
      regulated, 715 down-regulated), and 5177 (2702 up-regulated, 2475 down-regulated)
      genes from the cold-treated samples at 6, 24 and 72 h, respectively. The accuracy
      of the RNA-seq derived transcript expression data was validated by analyzing the
      expression patterns of 17 DEGs by qPCR. Plant hormone signal transduction, plant
      pathogen interaction, and secondary metabolism were the most significantly
      enriched GO categories amongst in the DEGs. A total of 60 transcription factors
      were shown to be cold responsive. In addition, a number of genes involved in the
      catabolism and signaling of hormones, such as abscisic acid, ethylene and
      gibberellin, were affected by the cold stress. Meanwhile, levels of putrescine
      progressively increased under cold, which was consistent with up-regulation of an
      arginine decarboxylase gene. CONCLUSIONS: This dataset provides valuable
      information regarding the trifoliate orange transcriptome changes in response to
      cold stress and may help guide future identification and functional analysis of
      genes that are importnatn for enhancing cold hardiness.

PMID- 26219961
TI  - Comparison of corneal endothelial cell measurements by two non-contact specular
      microscopes.
AB  - BACKGROUND: Measurement of corneal endothelial cell density is important both for
      clinical diagnosis as well as clinical studies. Since endothelial cell loss is
      considered irreversible in humans, even small changes in endothelial cell density
      are relevant. Therefore it is important to know whether different instruments for
      endothelial cell density measurements give the same results and can thus be used
      interchangeably. In this study we compare corneal endothelial cell density and
      morphometry measurements from two widely used non-contact specular microscopes,
      the Topcon SP3000P and Konan Noncon Robo SP8000. METHODS: Endothelial cell
      measurements were performed with both the Topcon SP3000P and Konan Noncon Robo
      SP8000 on 34 eyes of 18 consecutive patients of our cornea clinics with poor
      image quality being the only exclusion criterion. Images were obtained using the
      auto-focussing method and manual cell selection. Endothelial cell density (ECD),
      hexagonal cell ratio (HEX) and coefficient of value (CV) of the endothelial cell
      layer were calculated by the instruments' built-in software. RESULTS: ECD values
      calculated by the Konan were systematically higher than Topcon values: in 94 % of
      eyes Konan gave a higher value than Topcon, leading to a mean difference in ECD
      between the instruments of 187 cells/mm(2) (P < 0.001 in paired Wilcoxon test).
      HEX showed a broad range of values and differed greatly with only weak
      correlation between the two instruments. CV values for Konan mostly exceeded
      Topcon values, and only showed a weak correlation between the two instruments as
      well. CONCLUSIONS: Values for ECD between the Konan and the Topcon do correlate
      well, but the ECDs calculated by the Konan are systematically higher than Topcon
      values. Both HEX and CV vary greatly and do not correlate sufficiently. Thus we
      recommend not to use the Konan and the Topcon instrument interchangeably.

PMID- 26219962
TI  - The Plasmodium berghei translocon of exported proteins reveals spatiotemporal
      dynamics of tubular extensions.
AB  - The erythrocyte is an extraordinary host cell for intracellular pathogens and
      requires extensive remodelling to become permissive for infection. Malaria
      parasites modify their host red blood cells through protein export to acquire
      nutrients and evade immune responses. Endogenous fluorescent tagging of three
      signature proteins of the Plasmodium berghei translocon of exported proteins
      (PTEX), heat shock protein 101, exported protein 2 (EXP2), and PTEX88, revealed
      motile, tubular extensions of the parasitophorous vacuole that protrude from the
      parasite far into the red blood cell. EXP2 displays a more prominent presence at
      the periphery of the parasite, consistent with its proposed role in pore
      formation. The tubular compartment is most prominent during trophozoite growth.
      Distinct spatiotemporal expression of individual PTEX components during sporogony
      and liver-stage development indicates additional functions and tight regulation
      of the PTEX translocon during parasite life cycle progression. Together, live
      cell imaging and correlative light and electron microscopy permitted previously
      unrecognized spatiotemporal and subcellular resolution of PTEX-containing tubules
      in murine malaria parasites. These findings further refine current models for
      Plasmodium-induced erythrocyte makeover. 

PMID- 26219964
TI  - [EpiReumaPt - development and consequences].

PMID- 26219963
TI  - Hypoxia accelerates vascular repair of endothelial colony-forming cells on
      ischemic injury via STAT3-BCL3 axis.
AB  - INTRODUCTION: Endothelial colony-forming cells (ECFCs) significantly improve
      tissue repair by providing regeneration potential within injured cardiovascular
      tissue. However, ECFC transplantation into ischemic tissue exhibits limited
      therapeutic efficacy due to poor engraftment in vivo. We established an adequate
      ex vivo expansion protocol and identified novel modulators that enhance
      functional bioactivities of ECFCs. METHODS: To augment the regenerative potential
      of ECFCs, functional bioactivities of hypoxia-preconditioned ECFCs (hypo-ECFCs)
      were examined. RESULTS: Phosphorylations of the JAK2/STAT3 pathway and clonogenic
      proliferation were enhanced by short-term ECFC culturing under hypoxia, whereas
      siRNA-targeting of STAT3 significantly reduced these activities. Expression of
      BCL3, a target molecule of STAT3, was increased in hypo-ECFCs. Moreover, siRNA
      inhibition of BCL3 markedly reduced survival of ECFCs during hypoxic stress in
      vitro and ischemic stress in vivo. In a hindlimb ischemia model of ischemia, hypo
      ECFC transplantation enhanced blood flow ratio, capillary density, transplanted
      cell proliferation and survival, and angiogenic cytokine secretion at ischemic
      sites. CONCLUSIONS: Hypoxia preconditioning facilitates functional bioactivities
      of ECFCs by mediating regulation of the STAT3-BCL3 axis. Thus, a hypoxic
      preconditioned ex vivo expansion protocol triggers expansion and functional
      bioactivities of ECFCs via modulation of the hypoxia-induced STAT3-BCL3 axis,
      suggesting that hypo-ECFCs offer a therapeutic strategy for accelerated
      neovasculogenesis in ischemic diseases.

PMID- 26219965
TI  - EpiReumaPt- the study of rheumatic and musculoskeletal diseases in Portugal: a
      detailed view of the methodology.
AB  - Rheumatic and musculoskeletal diseases (RMD) are prevalent and leading causes of
      disability and consumption of healthcare and social resources. EpiReumaPt is a
      national population-based survey developed by the Portuguese Society of
      Rheumatology that aimed to estimate the prevalence of RMDs and determine their
      impact on function, quality of life, mental health and use of healthcare
      resources. This article describes in detail the design, methodology and planned
      analyses of EpiReumaPt. Recruitment started in September 2011 and finished in
      December 2013. This study involved a three-stage approach. The first step was a
      face-to-face survey performed by trained interviewers at the household of 10,661
      subjects who where randomly selected by a stratified multistage sampling. A
      highly sensitive screening questionnaire for RMDs was used. Secondly,
      participants who screened positive (64%) for at least one RMD as well as 20% of
      individuals with a negative screening were invited for assessment by a
      rheumatologist. In total, 3,877 subjects participated in this second phase, where
      they were also invited to donate a blood sample to be stored at the Biobanco-IMM.
      History and physical examination, followed by appropriate laboratory and imaging
      tests were performed. At the end of the visit, the rheumatologist established a
      diagnosis. Finally, a team of three experienced rheumatologists reviewed all the
      clinical data and defined the diagnoses according to previously validated
      criteria. The EpiReumaPt dataset, containing data from several questionnaires,
      various clinical measurements and information from laboratory and imaging tests,
      comprises an invaluable asset for research. The large amount of information
      collected from each participant and the large number of participants, with a wide
      age range covering and being representative of the adults from the entire
      country, makes EpiReumaPt the largest study of RMDs performed in Portugal. 

PMID- 26219966
TI  - EpiReumaPt: how to perform a national population based study - a practical guide.
AB  - BACKGROUND: The aim of this article was to describe and discuss several
      strategies and standard operating procedures undertaken in the EpiReumaPt study -
      which was the first Portuguese, national, cross-sectional population-based study
      of Rheumatic and Musculoskeletal Diseases (RMD). METHODS: The technical
      procedures, legal issues, management and practical questions were studied,
      analyzed and discussed with relevant stakeholders. During the 1st phase of
      EpiReumaPt the coordination team and Centro de Estudos de Sondagens e Opiniao
      (CESOP) worked to recruit and interview 10,661 subjects. The 2nd phase involved
      the participation of a multidisciplinary team, several local authorities, a
      specialized vehicle ("mobile unit") and a specific software program for the
      clinical appointments. The development of specific recruitment strategies
      improved the participation rate. Blood samples were collected and sent to
      Biobanco-IMM and to a central lab for immediate measurements. In the 3rd phase
      the RMD diagnosis were validated by a team of three experienced rheumatologists -
      clinical data, imaging and lab test results were revised according to previously
      published classification criteria. CONCLUSION: EpiReumaPt was a nationwide
      project successfully conducted, which followed critical logistic/coordination and
      research strategies. EpiReumaPt methodology and coordination could be used as an
      example for other epidemiologic endeavors and public health policies.

PMID- 26219967
TI  - Clinical significance of matrix metalloproteinase-3 in systemic lupus
      erythematosus patients: a potential biomarker for disease activity and damage.
AB  - OBJECTIVES: To assess the serum level of matrix metalloproteinase-3 (MMP-3) in
      systemic lupus erythematosus (SLE) patients and correlate it with clinical
      manifestations, laboratory findings, disease activity and damage. METHODS: Forty
      two female SLE patients were included in the present study. Full history taking,
      thorough examination and investigations were performed. Disease activity was
      assessed using the SLE disease activity index (SLEDAI). Furthermore, Systemic
      Lupus International Collaborating Clinics /American College of Rheumatology
      damage index (SLICC/ACR DI) was also assessed. Renal biopsy was done in those
      with lupus nephritis. Thirty age and sex matched subjects were included as
      control. Serum MMP-3 was measured by ELISA. RESULTS: The mean serum MMP-3 level
      in SLE patients was significantly higher (80.9+/-45.8 ng/ml) than in the control
      (10.01+/-2.6 ng/ml) (p <0.0001). The level in patients with arthritis, nephritis
      or hematologic disorders were significantly higher than in those without
      (p<0.0001, p=0.02 and p=0.04 respectively). The MMP-3 was significantly different
      among the subclasses of renal biopsy (p=0.01) being higher in those with class IV
      (137.5+/-45.6 ng/ml). It significantly correlated with the SLEDAI, SLICC, white
      blood cells and platelet counts (r=0.37, p=0.02; r=0.36, p=0.02; r=0.32, p 0.04
      and r=0.38, p=0.01 respectively). On linear regression analysis with age, disease
      duration and body mass index as independent factors, the SLEDAI and SLICC were
      not significant predictors. CONCLUSION: Serum MMP-3 was found to be high in SLE
      patients and associated with arthritis, nephritis and hematological
      manifestations. Matrix metalloproteinase-3 correlated with disease activity and
      damage making it a possible biomarker and its measure of considerable interest
      related to the potential therapeutic responses and disease outcome.

PMID- 26219968
TI  - High levels of serum hyaluronic acid in adults with dermatomyositis.
AB  - BACKGROUND / OBJECTIVES: Hyaluronic acid (HA) is rarely described in
      dermatomyositis (DM). Thus, we determined any clinical association of serum
      levels of hyaluronic acid (HA) in patients with dermatomyositis (DM). MATERIALS
      AND METHODS: This cross-sectional single-center analysis 75 DM and 75 healthy
      individuals, during the period from January 2012 to July 2013. An anti-HA
      antibody assay was performed using specific ELISA/EIA kits, according to the
      manufacturer's protocol. RESULTS: The patients with DM and control subjects had
      comparable demographic distributions (p>0.05). The median time duration between
      disease diagnosis and initial symptoms was 6.0 [3.0-12.0] months, with a median
      DM disease duration of 4.0 [1.0-7.0] years. The median level of serum HA was
      significantly increased in patients with DM compared to the control group [329.0
      (80.0-958.0) vs. 133.0 (30.0-262.0) ng/mL, respectively; p<0.001]. Additional
      analysis involving patients with DM showed that the serum level of HA did not
      correlate with age, duration between disease diagnosis and initial symptoms,
      disease duration, disease status, serum muscle enzyme levels or cumulative
      prednisolone dose (p>0.05). Serum HA also did not correlate with gender,
      ethnicity, auto-antibodies or drug use (p>0.05), but did correlate with cutaneous
      features, such as photosensitivity (p=0.001), "shawl" sign (p=0.018), "V-neck"
      sign (p=0.005) and cuticular hypertrophy (p=0.014). CONCLUSIONS: A high level of
      serum AH was observed in DM compared to healthy individuals. In DM, HA did not
      correlate to demographic, auto-antibodies and therapy parameters. However, HA
      correlated specifically with some cutaneous features, suggesting that this
      glycosaminoglycan could be involved in modulating cutaneous inflammation in this
      population. More studies are necessary to understand the correlation between AH
      and patients with DM.

PMID- 26219969
TI  - Circulating adipokines and organ involvement in patients with systemic sclerosis.
AB  - BACKGROUND: In recent years, mediators synthesized in the adipose tissue, the so
      called adipokines, have been reported to play important roles in the pathogenesis
      of autoimmune rheumatic diseases. OBJECTIVE: To compare serum leptin, adiponectin
      and resistin levels in patients with systemic sclerosis (SSc) and healthy
      controls. To find possible relationship between serum levels of adipokines and
      organ involvement with focus on interstitial lung disease in SSc patients.
      PATIENTS AND METHODS: Lung involvement was assessed functionally (body
      plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO) and
      six-minute walk test) and radiologically (using average disease extent on high
      resolution computed tomography (HRCT) of the lungs according to the percentage of
      interstitial changes) in 29 SSc patients. Quantitative sandwich ELISA was used to
      measure resistin, leptin and adiponectin concentrations in sera of patients and
      30 healthy controls. RESULTS: We found no statistically significant differences
      in serum resistin, leptin and adiponectin levels between SSc patients and the
      controls. However, serum adiponectin concentrations were significantly lower in
      active than in inactive patients, they also correlated positively with vital
      capacity (VC) (p=0.04) and negatively with Valentini activity score (p=0.04).
      Serum resistin levels were significantly elevated in patients with digital ulcers
      (p=0.03) and serum concentrations of leptin were associated with the duration of
      SSc symptoms other than Raynaud's phenomenon (p<0.01) CONCLUSIONS: Serum
      adiponectin should be further investigated as a candidate for SSc activity marker
      and resistin may play a role in ulcer development in SSc patients.

PMID- 26219971
TI  - Pigmented Villonodular Synovitis: a recurrent case with atypical location and
      extra-articular extension.
AB  - Pigmented Villonodular Synovitis (PVNS) remains a diagnostic challenge because of
      its non-specific presentation and subtle radiological findings. This uncommon
      entity is characterized by a benign synovial membrane proliferation of joints,
      tendon sheaths and bursas. The authors report a case of recurrent PVNS affecting
      an uncommon location (the first left metatarsophalangeal joint), which extended
      well beyond the joint margins on recurrence, in a patient with non-specific
      complaints of joint pain and swelling. 

PMID- 26219970
TI  - Benefit of intravenous immunoglobulin in a patient with longstanding
      polymyositis/systemic sclerosis overlap syndrome.
AB  - The authors describe the case of a 49 years old female with a progressive
      tetraparesis with two years of evolution, whose diagnostic study revealed a
      polymyositis/systemic sclerosis overlap syndrome. The patient was completely
      dependent and bedridden and had pulmonary, gastrointestinal, skin and bone
      involvement. This case intends to report and document that the use of "last-line"
      treatments such as intravenous immunoglobulins are effective and can be a therapy
      of great impact on the quality of life of the patient, even when apparently
      irreversible injury is established. 

PMID- 26219972
TI  - Propylthiouracil induced pulmonary-renal syndrome: a case report.
AB  - Propylthiouracil (PTU) is known to induce antineutrophil cytoplasmatic antibody
      (ANCA) seropositivity; however, small vessel vasculitis (SVV) with pulmonary and
      renal involvement is rare. We present the case of an 81-year-old woman on PTU
      treatment due to toxic nodular goitre who developed alveolar hemorrhage and
      rapidly progressive glomerulonephritis. The authors highlight the importance of
      early recognising drug-induced pulmonary-renal syndrome (PRS) in order to avoid
      unnecessary tests, a delay in the diagnosis and evolution to end-stage kidney
      disease or life-threatening conditions. 

PMID- 26219973
TI  - [Polyarteritis nodosa: the angiography usefulness].

PMID- 26219974
TI  - Persistent abdominal pain after exercise: an unexpected diagnosis.
AB  - Painful conditions of the musculoskeletal system are encountered quite frequently
      and are generally benign. However, clinicians should be careful to exclude rare
      malignant disorders and soft tissue sarcomas such as rhabdomyosarcoma, which have
      no specific symptoms or findings. This paper presents a case that was initially
      consistent with a hematoma but was then diagnosed as a rhabdomyosarcoma upon
      clinical examination and ultrasonography at follow-up shortly after. 

PMID- 26219975
TI  - CAND1 exchange factor promotes Keap1 integration into cullin 3-RING ubiquitin
      ligase during adipogenesis.
AB  - Adipogenesis is governed by a plethora of regulatory proteins which are most
      commonly controlled by the ubiquitin proteasome system. Here, we show that the
      differentiation of LiSa-2 preadipocytes is associated with an increase of cullin
      associated and neddylation-dissociated 1 (CAND1), COP9 signalosome (CSN),
      neddylated cullin 3 (Cul3) and the BTB protein Keap1. Silencing of CAND1 leads to
      a decrease and reduced integration of Keap1 into Cul3-RING ubiquitin ligases
      (CRL3) and to a retardation of adipogenesis. Transient transfection of LiSa-2
      cells with CAND1 targeting miRNA148a also reduces Keap1 and slowed down
      adipogenesis of LiSa-2 cells. These results demonstrate for the first time that
      CAND1 acts as a BTB-protein exchange factor for CRL3 complexes. The specific
      increase of neddylated Cul3 might be explained by the recruitment of Cul3 or CRL3
      in a membrane-bound location during adipogenesis. Together, the results show that
      during adipogenesis in LiSa-2 cells a CAND1-dependent remodeling and
      activation/neddylation of CRL3 complexes take place. 

PMID- 26219976
TI  - Interaction of SiO2 nanoparticles with neuronal cells: Ionic mechanisms involved
      in the perturbation of calcium homeostasis.
AB  - SiO2 nanoparticles (NPs), in addition to their widespread utilization in consumer
      goods, are also being engineered for clinical use. They are considered to exert
      low toxicity both in vivo and in vitro, but the mechanisms involved in the
      cellular responses activated by these nanoobjects, even at non-toxic doses, have
      not been characterized in detail. This is of particular relevance for their
      interaction with the nervous system: silica NPs are good candidates for
      nanoneuromedicine applications. Here, by using two neuronal cell lines (GT1-7 and
      GN11 cells), derived from gonadotropin hormone releasing hormone (GnRH) neurons,
      we describe the mechanisms involved in the perturbation of calcium signaling, a
      key controller of neuronal function. At the non-toxic dose of 20MUgmL(-1), 50nm
      SiO2 NPs induce long lasting but reversible calcium signals, that in most cases
      show a complex oscillatory behavior. Using fluorescent NPs, we show that these
      signals do not depend on NPs internalization, are totally ascribable to calcium
      influx and are dependent in a complex way from size and surface charge. We
      provide evidence of the involvement of voltage-dependent and transient receptor
      potential-vanilloid 4 (TRPV4) channels. 

PMID- 26219977
TI  - Age and Sex Differences in Rates of Influenza-Associated Hospitalizations in Hong
      Kong.
AB  - Few studies have explored age and sex differences in the disease burden of
      influenza, although men and women probably differ in their susceptibility to
      influenza infections. In this study, quasi-Poisson regression models were applied
      to weekly age- and sex-specific hospitalization numbers of pneumonia and
      influenza cases in the Hong Kong SAR, People's Republic of China, from 2004 to
      2010. Age and sex differences were assessed by age- and sex-specific rates of
      excess hospitalization for influenza A subtypes A(H1N1), A(H3N2), and
      A(H1N1)pdm09 and influenza B, respectively. We found that, in children younger
      than 18 years, boys had a higher excess hospitalization rate than girls, with the
      male-to-female ratio of excess rate (MFR) ranging from 1.1 to 2.4. MFRs of
      hospitalization associated with different types/subtypes were less than 1.0 for
      adults younger than 40 years except for A(H3N2) (MFR = 1.6), while all the MFRs
      were equal to or higher than 1.0 in adults aged 40 years or more except for
      A(H1N1)pdm09 in elderly persons aged 65 years or more (MFR = 0.9). No MFR was
      found to be statistically significant (P < 0.05) for hospitalizations associated
      with influenza type/subtype. There is some limited evidence on age and sex
      differences in hospitalization associated with influenza in the subtropical city
      of Hong Kong. 

PMID- 26219980
TI  - Factors affecting the work of physicians in rural areas of Turkey.
AB  - INTRODUCTION: An unbalanced geographical distribution of physicians leads to
      important differences in healthcare outcomes and difficulties in accessing
      healthcare services in rural areas. As in many other countries in the world, the
      geographical distribution of physicians in Turkey is unbalanced. Although there
      has been an increase in the number of physicians in the rural areas of Turkey
      since the introduction of the Health Transformation Program in 2003, health
      statistics indicate that significant differences still exist between regions in
      terms of the population-to-physician ratio. The aim of this study was to
      determine the factors that affect physicians' decisions about working in rural
      areas in Turkey. METHODS: Overall, 1340 physicians working in urban areas
      constituted the sample group of this study. A survey method was used to collect
      the data. The questionnaire, which was used as a data collection tool, included
      nine questions to gather the opinions of physicians regarding working in rural
      areas. Variables such as occupational group and financial incentives affecting
      the physicians' willingness to work in rural areas were analyzed with descriptive
      statistics, and the answers given according to these variables were compared via
      t-test and one-way analysis of variance. RESULTS: Of the sample, 59.9% of the
      participant physicians were men, and 36.9% were specialists. Opinions of the
      physicians about working in the rural areas differed significantly by
      occupational group, marital status and income. Medical residents and general
      practitioners were more willing to work in rural areas than other profession
      groups. In addition, single physicians were more open to working in rural areas
      than were married physicians. An increase in physicians' income reduced their
      willingness to work in rural areas. The developmental level of the region where
      they worked was found to be a very important variable affecting their
      preferences. Participants working in developed regions are reluctant to work in
      the rural areas. CONCLUSIONS: Specific occupational groups, young and single
      physicians, and physicians working in underdeveloped regions were found to be the
      groups that can more easily be motivated to work in rural areas. To encourage
      physicians to work in rural areas, monetary and non-monetary incentives should be
      considered.

PMID- 26219978
TI  - The molecular targets of approved treatments for pulmonary arterial hypertension.
AB  - Until recently, three classes of medical therapy were available for the treatment
      of pulmonary arterial hypertension (PAH)--prostanoids, endothelin receptor
      antagonists and phosphodiesterase type 5 (PDE5) inhibitors. With the approval of
      the soluble guanylate cyclase stimulator riociguat, an additional drug class has
      become available targeting a distinct molecular target in the same pathway as
      PDE5 inhibitors. Treatment recommendations currently include the use of all four
      drug classes to treat PAH, but there is a lack of comparative data for these
      therapies. Therefore, an understanding of the mechanistic differences between
      these agents is critical when making treatment decisions. Combination therapy is
      often used to treat PAH and it is therefore important that physicians understand
      how the modes of action of these drugs may interact to work as complementary
      partners, or potentially with unwanted consequences. Furthermore, different
      patient phenotypes mean that patients respond differently to treatment; while a
      certain monotherapy may be adequate for some patients, for others it will be
      important to consider alternating or combining compounds with different molecular
      targets. This review describes how the four currently approved drug classes
      target the complex pathobiology of PAH and will consider the distinct target
      molecules of each drug class, their modes of action, and review the pivotal
      clinical trial data supporting their use. It will also discuss the rationale for
      combining drugs (or not) from the different classes, and review the clinical data
      from studies on combination therapy.

PMID- 26219979
TI  - Which individuals are at increased risk of pneumococcal disease and why? Impact
      of COPD, asthma, smoking, diabetes, and/or chronic heart disease on community
      acquired pneumonia and invasive pneumococcal disease.
AB  - Pneumococcal disease (including community-acquired pneumonia and invasive
      pneumococcal disease) poses a burden to the community all year round, especially
      in those with chronic underlying conditions. Individuals with COPD, asthma or who
      smoke, and those with chronic heart disease or diabetes mellitus have been shown
      to be at increased risk of pneumococcal disease compared with those without these
      risk factors. These conditions, and smoking, can also adversely affect patient
      outcomes, including short-term and long-term mortality rates, following
      pneumonia. Community-acquired pneumonia, and in particular pneumococcal
      pneumonia, is associated with a significant economic burden, especially in those
      who are hospitalised, and also has an impact on a patient's quality of life.
      Therefore, physicians should target individuals with COPD, asthma, heart disease
      or diabetes mellitus, and those who smoke, for pneumococcal vaccination at the
      earliest opportunity at any time of the year. 

PMID- 26219981
TI  - VEGF induces stress fiber formation in fibroblasts isolated from dystrophic
      muscle.
AB  - Treatment with vascular endothelial growth factor (VEGF) to reduce ischemia and
      enhance both endogenous muscle repair and regenerative cell therapy in Duchenne
      muscular dystrophy (DMD) has been widely proposed in recent years. However, the
      interaction between angiogenesis and fibrosis, a hallmark feature of DMD, remains
      unclear. To date, it has not been determined whether VEGF exerts a pro-fibrotic
      effect on DMD-derived fibroblasts, which may contribute to further disease
      progression. Thus, the purpose of this study was to investigate the effect of
      exogenous VEGF on fibroblast cultures established from a murine model of DMD.
      Primary fibroblast cultures were established from gastrocnemius and diaphragm
      muscles of 10 week-old mdx/utrn+/- mice. Quantitative polymerase chain reaction
      (qPCR) was employed to assess changes in transcript expression of alpha-smooth
      muscle actin (Acta2), type-1 collagen (Col1a1), connective tissue growth factor
      (Ctgf/ccn2) and fibronectin (Fn1). Immunofluorescence and Western blot analysis
      was further employed to visualize changes in protein expression of alpha-smooth
      muscle actin (alpha-SMA), CTGF/CCN2 and fibronectin. mRNA levels of Col1a1,
      Ctgf/ccn2, and FN did not increase following treatment with VEGF in fibroblasts
      derived from either diaphragm or gastrocnemius muscles. Acta2 expression
      increased significantly in diaphragm-derived fibroblasts following treatment with
      VEGF. Morphological assessment revealed increased stress fiber formation in VEGF
      treated fibroblasts compared to the untreated control fibroblasts. The findings
      from this study suggest that further investigation into the effect of VEGF on
      fibroblast function is required prior to the utilization of the growth factor as
      a treatment for DMD. 

PMID- 26219982
TI  - ER and Golgi stresses increase ER-Golgi SNARE Syntaxin5: Implications for
      organelle stress and betaAPP processing.
AB  - Unresolved endoplasmic reticulum (ER) stress causes neuronal death and has been
      implicated in neurodegenerative conditions such as Alzheimer's disease (AD).
      However, the mechanisms by which stress signals propagate from the ER through the
      Golgi apparatus and their effects on the transport and processing of AD-related
      proteins, such as beta-amyloid precursor protein (betaAPP), are unknown. We
      recently found that in the NG108-15 cell line, ER stress upregulates ER-Golgi
      soluble N-ethylmaleimide-sensitive factor-attachment protein receptors (ER-Golgi
      SNAREs) Syx5 and Bet1. In the present study, we examined the effects of apoptosis
      and ER stress inducers on the expression of ER-Golgi SNARE proteins and cell
      viability in a primary culture of rat hippocampal neurons. An apoptosis inducer
      significantly downregulated the expression of ER-Golgi SNARE Syx5. ER-stress
      inducers upregulated the expression of Syx5 isoforms and Bet1 proteins via de
      novo synthesis of their mRNA transcripts. Knockdown of Syx5 during apoptosis or
      ER stress induction enhanced vulnerability of neurons. Additionally, we examined
      the effects of Golgi stress on Syx5 expression and betaAPP processing. Golgi
      stress also induced upregulation of ER-Golgi SNARE Syx5, and concomitantly,
      suppressed amyloid-beta peptide secretion. These findings suggest that Syx5 is a
      potential stress responsive factor that participates in betaAPP processing and
      the survival pathways of neuronal cells. 

PMID- 26219983
TI  - KCa1.1 is potential marker for distinguishing Ah-type baroreceptor neurons in NTS
      and contributes to sex-specific presynaptic neurotransmission in baroreflex
      afferent pathway.
AB  - Sexual-dimorphic neurocontrol of circulation has been described in baroreflex due
      largely to the function of myelinated Ah-type baroreceptor neurons (BRNs, 1st
      order) in nodose. However, it remains unclear if sex- and afferent-specific
      neurotransmission could also be observed in the central synapses within nucleus
      of solitary track (NTS, 2nd-order). According to the principle of no mixed
      neurotransmission among afferents and differentiation of Ah- and A-types to
      iberiotoxin (IbTX) observed in nodose, the 2nd-order Ah-type BRNs are highly
      expected. To test this hypothesis, the excitatory post-synaptic currents (EPSCs)
      were recorded in identified 2nd-order BRNs before and after IbTX using brain
      slice and whole-cell patch. These results showed that, in male rats, the dynamics
      of EPSCs in capsaicin-sensitive C-types were dramatically altered by IbTX, but
      not in capsaicin-insensitive A-types. Interestingly, near 50% capsaicin
      insensitive neurons in females showed similar effects to C-types, suggesting the
      existence of Ah-types in NTS, which may be the likely reason why the females had
      lower blood pressure and higher sensitivity to aortic depressor nerve stimulation
      via KCa1.1-mediated presynaptic glutamate release from Ah-type afferent
      terminals. 

PMID- 26219984
TI  - Sustained Arc expression in adult-generated granule cells.
AB  - The dentate gyrus (DG) plays a critical role in memory formation and maintenance.
      Fitting this specialized role, the DG has many unique characteristics. In
      addition to being one of the few places in which new neurons are continually
      added in adulthood, the region also shows a unique long-term sustained
      transcriptional response of the immediate-early gene Arc to sensory input.
      Although we know that adult-generated granule cells are reliably recruited into
      behaviorally-driven neuronal network, it remains unknown whether they display
      robust late-phase sustained transcription in response to activity like their
      developmentally-generated counterparts. Since this late-phase of transcription is
      required for enduring plasticity, knowing if sustained transcription appears as
      soon as these cells are incorporated provides information on their potential for
      plasticity. To address this question, adult F344 rats were injected with BrdU
      (50mg/kg/day for 5 days) and 4 weeks later explored a novel environment. Arc
      expression in both BrdU- and BrdU+ neurons was determined 0.5h, 1h, 2h, 6h, 8h,
      12h, or 24h following this behavior. Recently-generated granule cells showed a
      robust sustained Arc expression following a discrete behavioral experience. These
      data provide information on a potential mechanism to sculpt the representations
      of events occurring within hours of each other to create uncorrelated
      representations of episodes despite a highly excitable population of neurons. 

PMID- 26219985
TI  - Chronic treatment with mood stabilizer lithium inhibits amphetamine-induced risk
      taking manic-like behaviors.
AB  - A lack of behavioral tests and animal models for manic-depressive bipolar
      disorder is recognized as an important factor limiting development of novel
      pharmaceutical treatments for the disorder. Repeated amphetamine-induced
      hyperactivity is a commonly used animal model for mania. However, hyperactivity
      represents only one facet of mania and is also seen in other disorders. Increased
      engagement in risk taking behavior is frequently observed in the manic phase of
      bipolar disorder. In the present study, we analyzed the effect of the most
      commonly used mood stabilizer lithium on repeated amphetamine treatment-induced
      risk-taking behaviors in rats using elevated plus maze and wire-beam bridge
      tests. We found that repeated amphetamine treatment not only increased locomotor
      activity, but also increased risk taking behaviors in rats, and further that
      chronic lithium treatment inhibited the amphetamine-increased risk taking
      behavior. Our studies suggest that these tests may be useful tools to analyze the
      pharmacological validity of new and improved anti-manic drugs in animals. 

PMID- 26219986
TI  - Abnormal surround inhibition does not affect asymptomatic limbs in people with
      cervical dystonia.
AB  - Surround inhibition is a neural mechanism hypothesized to facilitate goal
      directed action by disinhibiting agonist muscle activity while simultaneously
      inhibiting antagonist and other uninvolved muscle activity. The present study was
      designed to investigate if abnormalities in surround inhibition are found in
      asymptomatic body parts (the hand) of people with focal cervical dystonia (neck).
      Participants with (n=7) and without (n=17) cervical dystonia completed a protocol
      in which they abducted their index finger while EMG was recorded from the first
      dorsal interosseous (agonist) and abductor digiti minimi (uninvolved) muscles.
      Transcranial magnetic stimulation was delivered over the primary motor cortex at
      intervals ranging from 0 to 950+ms after the onset of agonist muscle activity.
      Motor-evoked potential (MEP) amplitudes from both muscles were compared. In
      control participants, MEPs from the uninvolved muscle were significantly lower
      than agonist MEPs at intervals from 0 to 480ms. Similarly, in the hands of
      participants with cervical dystonia - the asymptomatic body part - MEPs from the
      uninvolved muscle were significantly lower than agonist MEPs from 0 to 175ms.
      These findings suggest that surround inhibition in people with focal dystonia may
      be intact in asymptomatic hands. In other words, abnormalities in surround
      inhibition may be restricted to the dystonic limb. 

PMID- 26219987
TI  - Cerebellar vermis contributes to the extinction of conditioned fear.
AB  - The cerebellum is known to contribute to the acquisition and retention of
      conditioned motor and emotional responses. Eyeblink conditioning and fear
      conditioning have been studied in greatest detail. Whereas a considerable number
      of studies have shown that the cerebellum is also involved in extinction of
      conditioned eyeblink responses, the likely contribution of the cerebellum to
      extinction of conditioned fear responses has largely been ignored. In the present
      study, we analyzed functional brain imaging data (fMRI) of previous work
      investigating extinction of conditioned fear in 32 young and healthy men, in
      which event-related fMRI analysis did not include the cerebellum. This dataset
      was analyzed using a spatial normalization method optimized for the cerebellum.
      During fear acquisition, an unpleasant electric shock (unconditioned stimulus;
      US) was paired with one of two pictures of geometrical figures (conditioned
      stimulus; CS+), while the other picture (CS-) was never paired with the US.
      During extinction, CS+ and CS- were presented without the US. During the
      acquisition phase, the fMRI signal related to the CS+ was significantly higher in
      hemispheric lobule VI in early compared to late acquisition (p<.05, permutation
      corrected). During the extinction phase, the fMRI signal related to the contrast
      CS+>CS- was significantly higher within the anterior vermis in early compared to
      late extinction (p<.05, permutation corrected). The present data show that the
      cerebellum is not only associated with the acquisition but also with the
      extinction of conditioned fear. 

PMID- 26219988
TI  - Sirt1-deficiency causes defective protein quality control.
AB  - Protein quality control is an important mechanism to maintain cellular
      homeostasis. Damaged proteins have to be restored or eliminated by degradation,
      which is mainly achieved by molecular chaperones and the ubiquitin-proteasome
      system. The NAD(+)-dependent deacetylase Sirt1 has been reported to play positive
      roles in the regulation of cellular homeostasis in response to various stresses.
      However, its contribution to protein quality control remains unexplored. Here we
      show that Sirt1 is involved in protein quality control in both an Hsp70-dependent
      and an Hsp70-independent manner. Loss of Sirt1 led to the accumulation of
      ubiquitinated proteins in cells and tissues, especially upon heat stress, without
      affecting proteasome activities. This was partly due to decreased basal
      expression of Hsp70. However, this accumulation was only partially alleviated by
      overexpression of Hsp70 or induction of Hsp70 upon heat shock in Sirt1-deficient
      cells and tissues. These results suggest that Sirt1 mediates both Hsp70-dependent
      and Hsp70-independent protein quality control. Our findings cast new light on
      understanding the role of Sirt1 in maintaining cellular homeostasis. 

PMID- 26219989
TI  - Neuroprotective effects of intravenous transplantation of bone marrow mononuclear
      cells from 5-fluorouracil pre-treated rats on ischemic stroke.
AB  - Our previous findings showed bone marrow mononuclear cells (BMMNCs) from 5-
      fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic
      efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats.
      This study was undertaken to explore the potential mechanisms underlying the
      neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat
      model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected
      at different time points. The contents of growth factors in the supernatant and
      CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO
      was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre
      treatment were independently transplanted via the tail vein 24h later. The
      neurological function was evaluated before cell transplantation and at 24h, 7d
      and 14d after cell transplantation. Rats were sacrificed at 14d after cell
      transplantation, the brains were collected for TTC staining, infarct volume
      detection, NISSL staining, counting of viable cells in the CA1 region, and
      observation of transplanted cells. BMRMNCs had elevated expressions of growth
      factors as well as CXCR4 expression. Our results confirmed the better therapeutic
      effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume,
      improvement of neurological function and more viable cells in the hippocampus. In
      addition, more transplanted cells were found after BMRMNCs transplantation at 7
      days and 14 days although there was no marked difference at 14 days. These
      findings indicate that BMRMNCs transplantation may protect ischemic stroke, at
      least partially, via increasing the secretion of growth factors and migration to
      the injured site.

PMID- 26219990
TI  - Physical activity assessment in cystic fibrosis: A position statement.
AB  - BACKGROUND: The aim of this position statement was to inform the choice of
      physical activity tools for use within CF research and clinical settings.
      METHODS: A systematic review of physical activity tools to explore evidence for
      reliability, validity, and responsiveness. Narrative answers to "four key
      questions" on motion sensors, questionnaires and diaries were drafted by the core
      writing team and then discussed at the Exercise Working Group in ECFS Lisbon
      2013. RESULTS AND SUMMARY: Our current position is that activity monitors such as
      SenseWear or ActiGraph offer informed choices to facilitate a comprehensive
      assessment of physical activity, and should as a minimum report on dimensions of
      physical activity including energy expenditure, step count and time spent in
      different intensities and sedentary time. The DigiWalker pedometer offers an
      informed choice of a comparatively inexpensive method of obtaining some
      measurement of physical activity. The HAES represents an informed choice of
      questionnaire to assess physical activity. There is insufficient data to
      recommend the use of one diary over another. Future research should focus on
      providing additional evidence of clinimetric properties of these and new physical
      activity assessment tools, as well as further exploring the added value of
      physical activity assessment in CF.

PMID- 26219991
TI  - Identification and treatment of depression of older adults in primary care:
      findings from the Sao Paulo Ageing and Health Study.
AB  - BACKGROUND: Depression, diabetes and hypertension are major contributors to the
      global burden of disease; however, the majority of research on depression and co
      morbid conditions originates in high-income countries. OBJECTIVE: This study
      examines the depression identification rate and compares treatment rates of
      depression with those of diabetes and hypertension among elderly individuals
      served in primary care through the Family Health Program (FHP) in Sao Paulo,
      Brazil. METHOD: A total of 1558 Sao Paulo Ageing and Health Study participants
      (low-income adults >=65 years old living in Sao Paulo) registered in the FHP were
      included for analysis. Chart review was performed for participants with an
      International Classification of Diseases, 10th edition (ICD-10) depression
      diagnosis (from survey interview) to verify if depression was recorded for these
      individuals. Depression, diabetes and hypertension treatment were assessed based
      on clinical assessments and medication checks. RESULTS: Seventy-three
      participants (4.8%) had ICD-10 depression, 344 (23.2%) had confirmed diabetes and
      1207 (79.3%) had confirmed hypertension. The proportion of those identified with
      depression by medical chart review (n = 63 for individuals whose chart could be
      found) was 4.8% (n = 3). Nine individuals (12.3%) with ICD-10 depression were
      treated. Rates of diabetes and hypertension treatment were 72.4% and 77.4%,
      respectively. CONCLUSION: Levels of treatment of depression in older adults
      receiving care in the FHP is very low compared to treatment rates of diabetes and
      hypertension. Collaborative care effectiveness trials for the treatment of
      depression in the FHP are needed to improve the quality of depression care for
      this population.

PMID- 26219992
TI  - R.E.N.A.L. nephrometry score predicts postoperative recurrence of localized renal
      cell carcinoma treated by radical nephrectomy.
AB  - BACKGROUND: We investigated the association between the R.E.N.A.L. nephrometry
      score (RNS) and the postoperative recurrence of localized renal cell carcinoma
      (RCC). METHODS: We retrospectively analyzed a database comprising 91 patients
      with non-small localized RCC (pT1b-T2b) treated by radical nephrectomy at our
      hospital from January 2002 to March 2010. RNS was scored based on imaging
      findings at diagnosis. The Cox proportional hazards model was used to predict
      recurrence-free survival (RFS) and to calculate hazard ratio (HR). RESULTS: The
      median age at operation was 63 years (range, 30-85 years). Postoperative
      recurrence occurred in 19 patients (21 %). Median RNS sum was 9 (range, 5-11).
      High RNS sum (10-12) was significantly associated with RFS (P = 0.0012).
      Multivariate analysis revealed that high RNS sum [HR, 9.05; 95 % confidence
      interval (CI), 2.11-63.9; P = 0.0019] were significantly associated with RFS.
      Regarding each component of RNS, only the L component, which referred to tumor
      location relative to the polar line, was associated with RFS (HR, 15.0; 95 % CI,
      2.68-396; P = 0.0006). CONCLUSIONS: RNS was associated with RFS in cases of non
      small localized RCC (pT1b-2b), thus supporting its utility as a prognostic
      factor.

PMID- 26219993
TI  - Evaluation of Peripheral Vertical Nondegenerative Medial Meniscus Tears Treated
      With Trephination Alone at the Time of Anterior Cruciate Ligament Reconstruction.
AB  - PURPOSE: To determine (1) subjective results and incidence of symptomatic medial
      meniscus tears (MMTs) in patients treated with trephination alone compared with a
      control group without meniscus tears and (2) if trephination treatment resulted
      in a higher incidence of knee arthritis compared with controls with intact
      menisci. METHODS: Between 1997 and 2010, 419 patients met the inclusion criteria
      of having an isolated anterior cruciate ligament (ACL) tear, peripheral vertical
      nondegenerative MMT treated with trephination alone, no lateral meniscus tears,
      normal radiographs before surgery, and no bilateral knee involvement. A control
      group of 462 patients included patients who met the same criteria but without
      MMT. Objective data included International Knee Documentation Committee (IKDC)
      objective evaluation. Subjective data included IKDC and Cincinnati Knee Rating
      System (CKRS) scores. RESULTS: Objective follow-up was obtained for 191 patients
      in the study group and 200 patients in the control group (mean, 5.6 and 5.9
      years, respectively; range, 2 to 16 years). Subjective survey follow-up was
      obtained for 312 patients in the study group and 343 patients in the control
      group (mean, 7.0 and 7.1 years, respectively). The mean CKRS score was 91.8 +/-
      13.3 for the study group and 92.3 +/- 10.9 for the control group (P = .27). The
      mean IKDC score was 86.5 +/- 15.8 for the study group and 86.7 +/- 16.3 for the
      control group (P = .81). Subsequent MMTs occurred in 51 patients (16.3%) in the
      study group and 20 patients (5.8%) in the control group (P < .0001). IKDC
      radiographic ratings were normal for 95% of the study group and 92% of the
      control group (P = .18). CONCLUSIONS: Patients with peripheral nondegenerative
      MMTs treated with trephination alone had a 16.3% rate of subsequent symptomatic
      MMTs compared with 6% in patients with intact menisci. However, no statistically
      significant differences were found between groups for radiographic and subjective
      results. LEVEL OF EVIDENCE: Level III, therapeutic case control study.

PMID- 26219994
TI  - Sex Differences in Patients With CAM Deformities With Femoroacetabular
      Impingement: 3-Dimensional Computed Tomographic Quantification.
AB  - PURPOSE: To determine if significant differences exist between male and female
      CAM deformities using quantitative 3-dimensional (3D) volume and location
      analysis. METHODS: Retrospective analysis of preoperative computed tomographic
      (CT) scans for 138 femurs (69 from male patients and 69 from female patients)
      diagnosed with impingement from November 2009 to November 2011 was completed.
      Those patients who presented with hip complaints and had a history, physical
      examination (limited range of motion, positive impingement signs), plain
      radiographs (anteroposterior pelvis, 90 degrees  Dunn view, false profile view),
      and magnetic resonance images consistent with femoroacetabular impingement (FAI)
      and in whom a minimum of 6 months of conservative therapy (oral anti-inflammatory
      agents, physical therapy, and activity modification) had failed were indicated
      for arthroscopic surgery and had a preoperative CT scan. Scans were segmented,
      converted to point cloud data, and analyzed with a custom-written computer
      program. Analysis included mean CAM height and volume, head radius, and femoral
      version. Differences were analyzed using an unpaired t test with significance set
      at P < .05. RESULTS: Female patients had greater femoral anteversion compared
      with male patients (female patients, 15.5 degrees  +/- 8.3 degrees ; male
      patients, 11.3 degrees  +/- 9.0 degrees ; P = .06). Male femoral head radii were
      significantly larger than female femoral heads (female patients, 22.0 +/- 1.3 mm;
      male patients, 25.4 +/- 1.3 mm; P < .001). Male CAM height was significantly
      larger than that in female patients (female patients, 0.66 +/- 0.61 mm; male
      patients, 1.51 +/- 0.75 mm; P < .001). Male CAM volume was significantly larger
      as well (male patients, 433 +/- 471 mm(3); female patients, 89 +/- 124 mm(3); P <
      .001). These differences persisted after normalizing height (P < .001) and volume
      (P < .001) to femoral head radius. Average clock face distribution was from the
      1:09 o'clock position +/- the 2:51 o'clock position to the 3:28 o'clock position
      +/- the 1:59 o'clock position, with an average span from the 3:06 o'clock
      position +/- the 1:29 o'clock position (male patients, the 11:23 o'clock position
      +/- the 0:46 o'clock position to the 3:05 o'clock position +/- the 1:20 o'clock
      position; female patients, the 11:33 o'clock position +/- the 0:37 o'clock
      position to the 2:27 o'clock position +/- the 0:45 o'clock position). There were
      no differences in the posterior (P = .60) or anterior (P = .14) extent of CAM
      deformities. However, the span on the clock face of the CAM deformities varied
      when comparing men with women (male patients, the 3:43 o'clock position +/- the
      1:29 o'clock position; female patients, the 2:54 o'clock position +/- the 1:09
      o'clock position; P = .02). CONCLUSIONS: Our data show that female CAM
      deformities are shallower and of smaller volume than male lesions. Further
      studies will allow further characterization of the 3D geometry of the proximal
      femur and provide more precise guidance for femoral osteochondroplasty for the
      treatment of CAM deformities. CLINICAL RELEVANCE: Female CAM deformities may not
      be detectable using current 2D nonquantitative methods. These findings should
      raise the clinician's index of suspicion when diagnosing a symptomatic CAM lesion
      in female patients.

PMID- 26219995
TI  - Behavioral and psychological symptoms among Indian patients with mild cognitive
      impairment.

PMID- 26219996
TI  - Delivery strategy for foetuses with cervical mass: The EXIT procedure.

PMID- 26219997
TI  - Erratum: Characterization of functional methylomes by next-generation capture
      sequencing identifies novel disease-associated variants.

PMID- 26219998
TI  - Landscape ecology of Trypanosoma cruzi in the southern Yucatan Peninsula.
AB  - Landscape interactions of Trypanosoma cruzi (Tc) with Triatoma dimidiata (Td)
      depend on the presence and relative abundance of mammal hosts. This study
      analyzed a landscape adjacent to the Calakmul Biosphere Reserve, composed of
      conserved areas, crop and farming areas, and the human community of Zoh Laguna
      with reported Chagas disease cases. Sylvatic mammals of the Chiroptera, Rodentia,
      and Marsupialia orders were captured, and livestock and pets were sampled along
      with T. dimidiata in all habitats. Infection by T. cruzi was analyzed using mtDNA
      markers, while lineage and DTU was analyzed using the mini-exon. 303 sylvatic
      specimens were collected, corresponding to 19 species during the rainy season and
      114 specimens of 18 species during dry season. Five bats Artibeus jamaicensis,
      Artibeus lituratus, Sturnira lilium, Sturnira ludovici, Dermanura phaeotis (Dp)
      and one rodent Heteromys gaumeri were collected in the three habitats. All but
      Dp, and including Carollia brevicauda and Myotis keaysi, were infected with
      predominately TcI in the sylvatic habitat and TcII in the ecotone. Sigmodon
      hispidus was the rodent with the highest prevalence of infection by T. cruzi I
      and II in ecotone and domestic habitats. Didelphis viginiana was infected only
      with TcI in both domestic and sylvatic habitats; the only two genotyped human
      cases were TcII. Two main clades of T. cruzi, lineages I (DTU Ia) and II (DTU
      VI), were found to be sympatric (all habitats and seasons) in the Zoh-Laguna
      landscape, suggesting that no species-specific interactions occur between the
      parasite and any mammal host, in any habitat. We have also found mixed infections
      of the two principal T. cruzi clades in individuals across modified habitats,
      particularly in livestock and pets, and in both haplogroups of T. dimidiata.
      Results are contradictory to the dilution hypothesis, although we did find that
      most resilient species had an important role as T. cruzi hosts. Our study
      detected some complex trends in parasite transmission related to lineage sorting
      within the matrix. Intriguingly, TcIa is dominant in terrestrial small wildlife
      in the sylvatic habitat and is the only parasite DTU found in D. virginiana in
      the domestic habitat, although its frequency remained constant in sylvatic and
      ecotone vectors. Bats have a key role in TcVI dispersal from the sylvatic
      habitat, while dogs, sheep, and humans are drivers of TcVI between domestic and
      ecotone habitats. Overall, our results allow us to conclude that T. cruzi
      transmission is dependent on host availability within a highly permeable
      landscape in Zoh Laguna. 

PMID- 26219999
TI  - Mild type 2 diabetes mellitus improves remote endothelial dysfunction after acute
      myocardial infarction.
AB  - AIMS: Myocardial infarction (MI) is a common cause of mortality in patients with
      diabetes mellitus (DM) and vascular dysfunction is a major component of diabetic
      cardiomyopathy. We investigated the systemic influence of acute MI on the
      diabetes-induced pathogenic changes in the rat aorta. METHODS: Nondiabetic Wistar
      (W) and type-2 diabetic Goto-Kakizaki (GK) rats underwent 45min of left anterior
      descending coronary artery occlusion followed by 24h of reperfusion. Isometric
      force was measured using organ bath. RESULTS: Plasma glucose-levels were
      significantly higher in diabetic rats (GK+sham: 13+/-2mM; GK+MI: 19+/-2mM)
      compared to nondiabetic rats (W+sham: 8+/-0mM; W+MI: 8+/-1mM). Acetylcholine
      induced relaxation was significantly weaker in rings from W+MI and GK+MI rats
      compared to corresponding sham-operated animals. Myocardial reperfusion injury
      was smaller in GK+MI than W+MI rats, and the concentration-response curves to
      acetylcholine were significantly enhanced in rings from GK+MI than W+MI rats.
      Nevertheless, the relaxation response to acetylcholine was similar in W+sham and
      GK+sham. Densitometric analysis of bands for endothelial nitric oxide synthase
      showed a significant decrease in W+MI rats compared to W+sham and GK+sham
      animals. Aortas from both GK+sham and GK+MI rats showed impaired contractile
      responses to phenylephrine in comparison with the nondiabetics. CONCLUSIONS: For
      the first time we showed that short-term and mild type-2 DM improved remote
      endothelial dysfunction after reperfused acute MI.

PMID- 26220007
TI  - [Provision of assistive devices in amyotrophic lateral sclerosis. Analysis of 3
      years case management in an internet-based supply network].
AB  - BACKGROUND: The provision of assistive devices (PAD) is a key element of care in
      amyotrophic lateral sclerosis (ALS). Since 2011, assistive devices (AD) have been
      coordinated in an internet-supported care network at university-based ALS centers
      in Berlin, Bochum, Hannover and Jena. The digitization of PAD processes has
      facilitated the evaluation of real-life ALS care. OBJECTIVES: Orthotics (OT),
      augmentative and alternative communication (AAC), supported treadmill (ST) and
      powered wheelchair (PW) were the PAD groups analyzed for delivery rates
      (proportion of delivered AD vs. medically indicated AD), rejection by patients
      and payers and latency of provision of care. RESULTS: Between June 2011 and
      October 2014 a total of 1479 patients and 12,478 AD were coordinated, among which
      3313 PAD were related to OT, AAC, ST or EM. The median delivery rate was 64.3 %.
      The mean rejection rate by patients was 9.8 % (OT 5.4 %, AAC 9.8 %, ST 10.2 % and
      PW 15.6 %). Marked differences were noted in the rejection rate by payers and in
      care provision latency: OT (16.2 %, 68 days, n = 734), AAC (30.4 %, 96 days, n =
      392), ST (34.8 %, 113 days, n = 164) and PW (35.6 %, 129 days, n = 259). Analysis
      of rejection rates showed significant differences among insurers. CONCLUSION:
      Only two thirds of the medically indicated AD reached the patients. Rejection
      rates by patients and payers and latency of provision of care were high. The PAD
      can substantially vary among health insurance companies. The establishment of
      consented criteria for PAD and their integration into treatment regimens and
      guidelines are crucial tasks for the future.

PMID- 26220008
TI  - 'On one's own strength' Healthcare providers' experience with introducing Marte
      Meo Counselling in dementia care.
AB  - AIM: The aim of the present action research study was to investigate the
      healthcare providers' experiences with introducing Marte Meo Counselling (MMC) in
      a dementia-specific care unit. BACKGROUND: Research on the use of MMC shows that
      healthcare providers saw the patients' resources and needs more clearly and
      achieved increased awareness of their own skills. DESIGN AND METHOD: An action
      oriented research including a three-phase strategy was applied: the mapping
      phase, the intervention phase and the evaluation phase. During the 5-month
      mapping phase, two researchers conducted participant observation of a total of 50
      hours. The intervention phase consisted of lectures, clinical supervision in MMC
      and seven reflection groups and lasted 12 months. In the six-month evaluation
      phase, participant observation of a total of 48 hours was conducted. Four focus
      group interviews took place during the whole study period of 2 years. RESULTS:
      The staff went through a process of change described by the following themes:
      from challenging behaviour to challenging interaction; from generalised skills to
      contextualised relational care; and from personal challenges to a professional
      community. CONCLUSIONS: As a result of MMC, the healthcare providers realised the
      value of taking into account the patients' context in dementia care and of being
      active participants in the patients' world. The focus changed from regarding
      challenging behaviour as symptoms of a disorder to being a challenge to
      interaction. IMPLICATIONS FOR PRACTICE: Marte Meo Counselling should be combined
      with continuous reflection to improve healthcare providers' interaction with
      people who live with dementia. The reflection groups gave the caregivers an
      opportunity for discussions that would otherwise be impossible in their busy
      everyday life.

PMID- 26220009
TI  - Characterisation of novel RUNX2 mutation with alanine tract expansion from
      Japanese cleidocranial dysplasia patient.
AB  - Cleidocranial dysplasia (CCD; MIM 119600) is an autosomal dominant skeletal
      dysplasia characterised by hypopalstic and/or aplastic clavicles, midface
      hypoplasia, absent or delayed closure of cranial sutures, moderately short
      stature, delayed eruption of permanent dentition and supernumerary teeth. The
      molecular pathogenesis can be explained in about two-thirds of CCD patients by
      haploinsufficiency of the RUNX2 gene. In our current study, we identified a novel
      and rare variant of the RUNX2 gene (c.181_189dupGCGGCGGCT) in a Japanese patient
      with phenotypic features of CCD. The insertion led an alanine tripeptide
      expansion (+3Ala) in the polyalanine tract. To date, a RUNX2 variant with alanine
      decapeptide expansion (+10Ala) is the only example of a causative variant of
      RUNX2 with polyalanine tract expansion to be reported, whilst RUNX2 (+1Ala) has
      been isolated from the healthy population. Thus, precise analyses of the RUNX2
      (+3Ala) variant were needed to clarify whether the tripeptide expanded RUNX2 is a
      second disease-causing mutant with alanine tract expansion. We therefore
      investigated the biochemical properties of the mutant RUNX2 (+3Ala), which
      contains 20 alanine residues in the polyalanine tract. When transfected in COS7
      cells, RUNX2 (+3Ala) formed intracellular ubiquitinated aggregates after 24h, and
      exerted a dominant negative effect in vitro. At 24h after gene transfection,
      whereas slight reduction was observed in RUNX2 (+10Ala), all of these mutants
      significantly activated osteoblast-specific element-2, a cis-acting sequence in
      the promoter of the RUNX2 target gene osteocalcin. The aggregation growth of
      RUNX2 (+3Ala) was clearly lower and slower than that of RUNX2 (+10Ala).
      Furthermore, we investigated several other RUNX2 variants with various alanine
      tract lengths, and found that the threshold for aggregation may be RUNX2 (+3Ala).
      We conclude that RUNX2 (+3Ala) is the cause of CCD in our current case, and that
      the accumulation of intracellular aggregates in vitro is related to the length of
      the alanine tract.

PMID- 26220010
TI  - Synergistic antidepressant-like effect of ferulic acid in combination with
      piperine: involvement of monoaminergic system.
AB  - The lifetime prevalence rate for major depressive disorder (MDD) is approximately
      17 % for most developed countries around the world. Dietary polyphenols are
      currently used as an adjuvant therapy to accelerate the therapeutic efficacy on
      depression. Ferulic acid (FA) or 4-hydroxy-3-methoxy-cinnamic acid (Fig. 1a) is a
      main polyphenolic component of Chinese herb Radix Angelicae Sinensis, which is
      found to have antidepressant-like effects through regulating serotonergic and
      noradrenergic function. The present study examined the synergistic effect of low
      doses of FA combined with subthreshold dose of piperine, a bioavailability
      enhancer, on depression-like behaviors in mice, and investigated the possible
      mechanism. The administration of FA, even in the highest dose tested, reduced
      immobility time by 60 % in the tail suspension and forced swimming tests (TST and
      FST) in mice when compared to control. The maximal antidepressant-like effect of
      FA was obtained with 200 mg/kg. In addition, piperine only produced a weak
      antidepressant-like effect in the TST and FST. However, the evidence from the
      interaction analysis suggested a synergistic effect when low doses of FA were
      combined with a subthreshold dose of piperine. Further neurochemical evidence
      such as monoamine levels in the frontal cortex, hippocampus, and hypothalamus and
      measurements of monoamine oxidase activity also supported a synergistic effect of
      FA and piperine in the enhancement of monoaminergic function. This finding
      supports the concept that the combination strategy might be an alternative
      therapy in the treatment of psychiatric disorders with high efficacy and low side
      effects.

PMID- 26220011
TI  - RCF1-dependent respiratory supercomplexes are integral for lifespan-maintenance
      in a fungal ageing model.
AB  - Mitochondrial respiratory supercomplexes (mtRSCs) are stoichiometric assemblies
      of electron transport chain (ETC) complexes in the inner mitochondrial membrane.
      They are hypothesized to regulate electron flow, the generation of reactive
      oxygen species (ROS) and to stabilize ETC complexes. Using the fungal ageing
      model Podospora anserina, we investigated the impact of homologues of the
      Saccharomyces cerevisiae respiratory supercomplex factors 1 and 2 (termed PaRCF1
      and PaRCF2) on mtRSC formation, fitness and lifespan. Whereas PaRCF2's role seems
      negligible, ablation of PaRCF1 alters size of monomeric complex IV, reduces the
      abundance of complex IV-containing supercomplexes, negatively affects vital
      functions and shortens lifespan. PaRcf1 overexpression slightly prolongs
      lifespan, though without appreciably influencing ETC organization. Overall, our
      results identify PaRCF1 as necessary yet not sufficient for mtRSC formation and
      demonstrate that PaRCF1-dependent stability of complex IV and associated
      supercomplexes is highly relevant for maintenance of the healthy lifespan in a
      eukaryotic model organism. 

PMID- 26220012
TI  - Using immunofluorescence (antigen) mapping in the diagnosis and classification of
      epidermolysis bullosa: a first report from Iran.
AB  - BACKGROUND: Immunofluorescence antigen mapping (IFM), is a newly introduced
      technique for diagnosis and classification of epidermolysis bullosa (EB) disease.
      The precise level of skin cleavage can be determined using monoclonal antibodies
      to EB-specific basement membrane zone protein. OBJECTIVE: To apply IFM technique
      in diagnosis and classification of EB and to identify utility and limitation of
      this method in our clinical setting. METHODS: IFM was done according to a
      described protocol by Pohla-Gubo et al. Monoclonal antibodies used for antigen
      mapping were against cytokeratin 5, cytokeratin 14, alpha6 integrin, beta4
      integrin, laminin 332, Collagen IV, and Collagen VII. RESULTS: IFM was done for
      95 referred patients, compromising 49 females and 46 males, aged 5 days to 45
      years (mean = 9.5 years). Ninety cases were diagnosed with EB and classified as
      follows: EB simplex: (n = 13), junctional EB (n = 14), dystrophic EB (n = 62),
      and Kindler syndrome (n = 1). Diagnosis was not made in five cases as their
      specimens contained no blister. Confirmatory genetic analysis was done for five
      junctional cases from two families with clinical features of laryngo-onycho
      cutaneous syndrome. Genetic molecular studies showed nonsense mutations in the
      last codon of exon 39 of the laminin alpha3a (LAMA3) gene (p.Gln57X) and a donor
      splice site mutation in LAMA3 (IVS57+5G>A) in the first and second family,
      respectively. CONCLUSION: IFM technique is relatively simple to perform, and
      interpretation of the results is not sophisticated. The proportion of
      inconclusive results will be decreased if the specimens contain freshly induced
      blister.

PMID- 26220013
TI  - Diabetes mellitus as risk factor for atrial fibrillation hospitalization:
      Incidence and outcomes over nine years in a region of Northern Italy.
AB  - AIMS: Diabetes mellitus (DM) and atrial fibrillation (AF) are worldwide public
      health challenges and major causes of death and cardiovascular events. The
      association between DM and AF is controversial in literature and data on outcomes
      of individuals with both diseases have not been evaluated in population studies.
      We tested the hypothesis that DM is independently associated to AF
      hospitalization and assessed the risk of stroke and mortality in people with both
      conditions. METHODS: We conducted a population-based cohort-study of DM patients
      and their corresponding controls identified in a administrative health database
      of the Lombardy Region. Both cohorts were followed for nine years. A
      multivariable Cox proportional-hazards-regression model was used to estimate the
      hazard ratio (HR) for first hospitalization for AF and for clinical outcomes.
      RESULTS: Out of 9,061,258 residents, 285,428 (3.14%) DM subjects were identified,
      mean age 65.8+/-15 years, 49% were women. The cumulative incidence of AF in DM
      was 10.4% vs. 7.4% in non-DM. DM was a risk factor for AF (HR 1.32, 95% CI 1.30
      1.34; p<0.0001). Oral anticoagulants were prescribed in 34.8% of DM patients with
      AF. DM associated with AF, presented the highest HR for stroke: 2.63; 95% CI 2.47
      2.80 and for total death, HR 2.41; 95% CI 2.36-2.47. CONCLUSIONS: In this
      population study, DM was an independent risk factor for AF hospitalization. DM
      patients with AF had the highest risk of stroke and total mortality. Early
      identification of AF and a structured plan to optimize the comprehensive
      management of DM and AF patients is mandatory.

PMID- 26220014
TI  - Can 'extrafine' dry powder aerosols improve lung deposition?
AB  - There is increasing interest in the use of so-called 'extrafine' aerosols to
      target the small airways in the management of asthma and COPD. Using previously
      presented deposition data, we assessed whether submicron (<1MUm) particles can
      improve central and deep lung deposition. Our data show instead that particles in
      the range 1-3MUm are much more relevant in this respect. Based on this finding
      the Symbicort Turbuhaler, Seretide Diskus, Rolenium Elpenhaler and Foster
      (Fostair) NEXThaler ICS/LABA combination DPIs were tested in vitro as a function
      of the pressure drop (2, 4 and 6kPa) across the inhaler. Obtained fine particle
      fractions (FPFs) <5MUm (as percent of label claim) were divided into subfractions
      <1, 1-3 and 3-5MUm. Differences of up to a factor of 4 were found between the
      best (Turbuhaler) and worst performing DPI (Elpenhaler), particularly for the FPF
      in the size range 1-3MUm. The NEXThaler, described as delivering 'extrafine'
      particles, did not appear to be superior in this size range. The marked
      differences in amount and size distribution of the aerosols between the devices
      in this study must cause significant differences in the total lung dose and drug
      distribution over the airways. 

PMID- 26220015
TI  - Formulation of a novel fixed dose combination of salmeterol xinafoate and
      mometasone furoate for inhaled drug delivery.
AB  - Co-administration of an inhaled corticosteroid and long acting beta agonist for
      chronic obstructive pulmonary disease has reduced mortality compared to either
      drug alone. This combination reduces exacerbations, hospitalization, emergency
      department visits and health care costs. A novel fixed-dose combination of the
      long acting beta-2 agonist salmeterol xinafoate (SX) and the corticosteroid
      mometasone furoate (MF) were prepared in a composite particle formulation as
      brittle matrix powder (BMP) and investigated for suitability as an inhaled
      combination product. In this study, BMP fixed dose combinations of SX and MF with
      or without stabilizing excipients (lactose, mannitol, glycine and trehalose) were
      prepared and characterized with respect to their thermal properties, morphology,
      aerodynamic performance and physical stability. BMP combination formulations of
      SX and MF exhibited improved aerodynamic properties when delivered by dry powder
      inhalation as compared to the micronized blends of the same substances.
      Aerodynamic evaluation was carried out by next generation pharmaceutical impactor
      (NGI) with a marketed DPI device. Results demonstrated that co-deposition
      occurred when SX and MF were formulated together as composite particles in a BMP,
      while physical blends resulted in inconsistent deposition and dose uniformity. As
      a result of the bottom-up particle engineering approach, combination BMP
      formulations allow for dual API composite formulations to be dispersed as
      aerosolized particles. Aerosolized BMP combination formulations resulted in
      delivered dose uniformity and co-deposition of each API. Further, an excipient
      free formulation, BMP SXMF, delivered approximately 50% of the loaded dose in the
      respirable range and demonstrated stability at ambient conditions for 6months.
      Single dose 24-h pharmacokinetic studies in rats demonstrated that lung tissue
      deposition and blood circulation (AUC0-24h) of two APIs were higher for the BMP
      combination group exhibiting a significantly higher lung concentration of drugs
      than for the crystalline physical blend. While high system drug levels are
      generally undesirable in lung targeted therapies, high blood levels in this
      rodent study could be indicative of increased pulmonary tissue exposure using BMP
      formulations. 

PMID- 26220017
TI  - Global Surgery: Cinderella no more?

PMID- 26220018
TI  - Progress towards overcoming coagulopathy and hemostatic dysfunction associated
      with xenotransplantation.
AB  - Dysregulation of coagulation and disordered hemostasis are frequent complications
      in the pig-to-nonhuman primate preclinical xenotransplantation model. The most
      extreme manifestations are the systemic development of a life-threatening
      consumptive coagulopathy, characterized by thrombocytopenia and bleeding, which
      is balanced at the opposite extreme by local complications of graft loss due to
      thrombotic microangiopathy. The contributing mechanisms include inflammation,
      vascular injury, heightened innate, humoral and cellular immune responses, and
      molecular incompatibilities affecting the regulation of coagulation. There also
      appear to be organ-specific factors that have been linked to vascular
      heterogeneity. As examples, liver xenografts rapidly induce thrombocytopenia by
      sequestering human/primate platelets; renal xenografts cause a broader
      coagulopathy, linked in some cases to reactivation of porcine CMV, whereas
      cardiac xenografts often succumb to microvascular thrombosis without associated
      systemic coagulopathy but with local perturbations in fibrinolysis. Overcoming
      coagulation dysfunction will require a combination of genetic and pharmacological
      strategies. Deletion of the xenoantigen alphaGal, transgenic expression of human
      complement regulatory proteins, and refinement of immunosuppression to blunt the
      antibody response have all had some impact, without providing a complete
      solution. More recently, the addition of approaches specifically targeted at
      coagulation have produced promising results. As an example, heterotopic cardiac
      xenografts from donors expressing human thrombomodulin have survived for more
      than a year in immunosuppressed baboons, with no evidence of thrombotic
      microangiopathy or coagulopathy. 

PMID- 26220016
TI  - A dual-axis approach to understanding neuroendocrine development.
AB  - This introduction sets out to present a series of paper about a novel perspective
      regarding stress and sex hormones, or what the authors within this special issue
      term "coupling" of hypothalamic-pituitary-adrenal and--gonadal axes. This view
      postulates that these axes do not necessarily operate in opposition, but can
      operate together as evidenced empirically as a positive within-person association
      between stress hormones like cortisol or sex hormones like testosterone. A wealth
      of papers within the special issue demonstrate positive coupling across acute,
      diurnal, basal, and longitudinal timeframes and across several different types of
      contexts. Reviews were meant to challenge whether this was physiologically
      plausible. Consistently, sophisticated statistical models were utilized in order
      to show a template for how to model positive coupling and to ensure that coupling
      was a within-person phenomenon. We cautiously considered positive coupling until
      the consistency of observing coupling was robust enough for us to consider
      challenging the prevailing oppositional view of these axes. We do so to
      acknowledge that there are contexts, moments and stages in which the function of
      these axes should work together: for example when contexts are both stressful and
      challenging or at developmental stages (like adolescence) in which the youth must
      grow up despite the storm and stress of youth. We hope that by putting forward a
      functional dual-axis approach, the field will be able to consider when and how
      these axes work together.

PMID- 26220019
TI  - Placental Regulation of Inflammation and Hypoxia after TNF-alpha Infusion in
      Mice.
AB  - PROBLEM: Increased levels of inflammatory cytokines are demonstrated in the serum
      of women with pre-eclampsia. TNF-alpha infusion in animal models induces
      proteinuric hypertension similar to human pre-eclampsia. The effect of TNF-alpha
      on regulation of the immune and hypoxic pathways in the developing placenta and
      their relationship with experimental pre-eclampsia remains unexamined. METHOD OF
      STUDY: TNF-alpha was infused into pregnant mice, and the effects on maternal
      hypertension, proteinuria, circulating levels of sFlt-1 and corresponding
      placental changes in molecules responding to inflammation (TLR-3 and TLR-4) and
      hypoxia (HIF-1alpha) were examined. RESULTS: TNF-alpha infusion resulted in
      maternal hypertension and proteinuria. Molecular changes in the placenta involved
      upregulation of TLR-3, TLR-4 and HIF-1alpha. Serum levels of sFlt-1 were high in
      pregnant animals, but not further upregulated by TNF-alpha infusion. CONCLUSION:
      A role for maladaptive regulation of TLR and HIF-1alpha induced by an imbalance
      in inflammatory cytokines is implicated in the pathogenesis of pre-eclampsia.

PMID- 26220021
TI  - The "corkscrew" sign.

PMID- 26220020
TI  - Effects of Yoga on Stress, Stress Adaption, and Heart Rate Variability Among
      Mental Health Professionals--A Randomized Controlled Trial.
AB  - BACKGROUND: Mental health professionals experiencing work-related stress may
      experience burn out, leading to a negative impact on their organization and
      patients. AIM: The aim of this study was to examine the effects of yoga classes
      on work-related stress, stress adaptation, and autonomic nerve activity among
      mental health professionals. METHODS: A randomized controlled trial was used,
      which compared the outcomes between the experimental (e.g., yoga program) and the
      control groups (e.g., no yoga exercise) for 12 weeks. Work-related stress and
      stress adaptation were assessed before and after the program. Heart rate
      variability (HRV) was measured at baseline, midpoint through the weekly yoga
      classes (6 weeks), and postintervention (after 12 weeks of yoga classes).
      RESULTS: The results showed that the mental health professionals in the yoga
      group experienced a significant reduction in work-related stress (t = -6.225, p <
      .001), and a significant enhancement of stress adaptation (t = 2.128, p = .042).
      Participants in the control group revealed no significant changes. Comparing the
      mean differences in pre- and posttest scores between yoga and control groups, we
      found the yoga group significantly decreased work-related stress (t = -3.216, p =
      .002), but there was no significant change in stress adaptation (p = .084). While
      controlling for the pretest scores of work-related stress, participants in yoga,
      but not the control group, revealed a significant increase in autonomic nerve
      activity at midpoint (6 weeks) test (t = -2.799, p = .007), and at posttest (12
      weeks; t = -2.099, p = .040). LINKING EVIDENCE TO ACTION: Because mental health
      professionals experienced a reduction in work-related stress and an increase in
      autonomic nerve activity in a weekly yoga program for 12 weeks, clinicians,
      administrators, and educators should offer yoga classes as a strategy to help
      health professionals reduce their work-related stress and balance autonomic nerve
      activities.

PMID- 26220022
TI  - Spatial distribution of infectious stages of the nematode Syngamus trachea within
      pheasant (Phasianus colchicus) release pens on estates in the South West of
      England: Potential density dependence?
AB  - The spatial distribution of the infectious stages of parasites with a direct life
      cycle is one of the most important factors influencing infectious disease
      dynamics, and acquisition rates will generally increase as the contact time
      between parasite and host increases. For animal species that are constrained by
      feeding opportunities, one might expect disease patterns to be highly skewed
      within confined systems. The aim of the present study was to identify to what
      extent, if any, eggs of avian parasites are aggregated within the release pen,
      and to evaluate what effect, if any, this aggregation had on the distribution of
      the adult stages within the host species. The abundance of Syngamus trachea eggs
      were highly aggregated within pens, with high levels of contamination driven by a
      combination of feeder placement, soil moisture and host-mediated heterogeneities
      in immuno-competence. The log mean and log variance of egg abundance was highly
      linear (R(2)=0.97-0.99), with an estimated slope (b) of between 1.79 and 1.97 for
      individual sites, and 2.11 when sites were combined, which indicated aggregation
      relative to an estimated Poisson slope of unity. Although the placement of
      feeders and environmental moisture could be contributing to parasite aggregation,
      density-dependent processes appear to be ensuring the population does not become
      too over or under-dispersed, in order to maintain the transmission-virulence
      equilibrium. To the best of our knowledge, this is the first paper to explicitly
      demonstrate the high spatial aggregation of eggs around feeding sites and the
      first to suggest possible density-dependent regulatory mechanisms stabilising
      disease dynamics between S. trachea and ring necked Pheasants (Phasianus
      colchicus). 

PMID- 26220023
TI  - Basic and clinical pharmacology contribution to extend anthelmintic molecules
      lifespan.
AB  - The correct use of pharmacology-based information is critical to design
      successful strategies for the future of parasite control in livestock animals.
      Integrated pharmaco-parasitological research approaches have greatly contributed
      to optimize drug activity. In an attempt to manage drug resistance in helminths
      of ruminants, combinations of two or more anthelmintics are being used or
      promoted, based on the fact that individual worms may have a lower degree of
      resistance to a multiple component formulation, when each chemical has a
      different mode of action compared to that observed when a single compound is
      used. However, as emphasized in the current review, the occurrence of potential
      pharmacokinetic and/or pharmacodynamic interactions between drug components
      highlights the need for deeper and integrated research to identify the advantages
      or disadvantages associated with the use of combined drug preparations. This
      review article provides integrated pharmacokinetic/pharmacodynamic and clinical
      pharmacology information pertinent to preserve the traditional and modern active
      ingredients as practical tools for parasite control. Novel pharmacological data
      on derquantel and monepantel, as representatives of modern anthelmintics for use
      in livestock, is summarized here. The article also summarizes the pharmaco
      parasitological knowledge considered critical to secure and/or extend the
      lifespan of the recently available novel molecules. 

PMID- 26220024
TI  - Dysfunctional amygdala activation and connectivity with the prefrontal cortex in
      current cocaine users.
AB  - OBJECTIVES: Stimulant use is associated with increased anxiety and a single
      administration of dexamphetamine increases amygdala activation to biologically
      salient stimuli in healthy individuals. Here, we investigate how current cocaine
      use affects amygdala activity and amygdala connectivity with the prefrontal
      cortex in response to biologically salient stimuli in an emotional face matching
      task (EFMT). EXPERIMENTAL DESIGN: Amygdala activity and amygdala connectivity
      during the EFMT were assessed in 51 cocaine using males and 32 non-drug-using
      healthy males using functional magnetic resonance imaging (fMRI). Within the
      cocaine use group, we explored whether amygdala activation was associated with
      age of first use of cocaine and duration of cocaine use to distinguish between
      amygdala activation alterations as a cause or a consequence of cocaine use.
      PRINCIPAL OBSERVATIONS: We observed hyperactivity of the amygdala, thalamus, and
      hippocampus and reduced amygdala connectivity with the anterior cingulate gyrus
      in response to angry and fearful facial expressions in current cocaine users
      compared to controls. Increased amygdala activation was independently associated
      with earlier age of first cocaine use and with longer exposure to cocaine.
      CONCLUSIONS: Our findings suggest that amygdala hyperactivity to biologically
      salient stimuli may represent a risk factor for an early onset of cocaine use and
      that prolonged cocaine use may further sensitize amygdala activation. High
      amygdala activation to emotional face processing in current cocaine users may
      result from low prefrontal control of the amygdala response to such stimuli.

PMID- 26220025
TI  - The AMC of medicine.

PMID- 26220026
TI  - Editor's note.

PMID- 26220027
TI  - Provider-centric models of care in which most consumers of healthcare are
      passive.

PMID- 26220028
TI  - What is the evidence status of Appropriate Use Criteria (AUC)? Insight from a
      matching exercise with the guidelines for echocardiography.
AB  - There is interest in adapting the American Appropriate Use Criteria (AUC) for
      transthoracic echocardiography to Australian practice. We matched 90 of 98 AUC
      with the guidelines (53 appropriate, 12 sometimes appropriate, 25 rarely
      appropriate), but eight lacked any match. Among the matched criteria, 76 (82%)
      indications were concordant with the guidelines. A stronger evidence base would
      be desirable to settle these discrepancies before Australian adoption of AUC. 

PMID- 26220029
TI  - Development of postgraduate research supervisors within a teaching hospital
      setting.
AB  - The recent trend to embed medical research at point of care has created a need
      for postgraduate research supervisors in hospitals who are practising clinicians
      and lab-based researchers. We explored the training needs of supervisors to
      inform the design and evaluation of a hospital-based development programme. We
      found that if hospital-based supervisors are to improve their practice, the
      programme needs to be on-site to ensure access and relevance to local issues. 

PMID- 26220030
TI  - Mobilisation of haemopoietic stem cells in teriparatide-treated patients.
AB  - Parathyroid hormone (PTH) is the predominant regulator of calcium/phosphate
      homeostasis in the human body. Beside this classical function, preclinical and
      clinical studies indicated a relevant role for PTH in mobilisation of bone marrow
      derived cells into peripheral blood. In addition, recombinant PTH (teriparatide)
      was recently approved for the treatment of severe osteoporosis. Therefore, it was
      the aim of the present study to investigate the dynamics of haemopoietic stem
      cells and corresponding in peripheral blood of 13 patients with osteoporosis
      during treatment with teriparatide. We were able to show that administration of
      teriparatide is sufficient to mobilise haemopoietic stem cells into the
      bloodstream accompanied by an alteration of mobilising cytokines. In conclusion,
      teriparatide might be a useful tool in the context of stem cell mobilisation. 

PMID- 26220031
TI  - An unusual cardiovascular adverse effect of donepezil.

PMID- 26220032
TI  - Beware the dog that didn't bark: a tale of creatinine in acute kidney injury.

PMID- 26220033
TI  - Unusual presentation of Epstein-Barr virus encephalitis in an older patient with
      a dramatic clinical response to intravenous immunoglobulin.

PMID- 26220034
TI  - Cardiac findings in obesity hypoventilation syndrome: is there a need for
      specific approach and evaluation?

PMID- 26220035
TI  - Author reply: To PMID 25370507.

PMID- 26220036
TI  - Improving ambulatory patient-centred practice with a patient teaching associate
      programme.

PMID- 26220037
TI  - Author reply: To PMID 23841759.

PMID- 26220038
TI  - Author reply: To PMID 25735580.

PMID- 26220039
TI  - Sustainability of deprescribing post discharge.

PMID- 26220041
TI  - Next-generation deep-sequencing detects multiple clones of CALR mutations in
      patients with BCR-ABL1 negative MPN.

PMID- 26220040
TI  - Impact of PTEN abnormalities on outcome in pediatric patients with T-cell acute
      lymphoblastic leukemia treated on the MRC UKALL2003 trial.
AB  - PTEN gene inactivation by mutation or deletion is common in pediatric T-cell
      acute lymphoblastic leukemia (T-ALL), but the impact on outcome is unclear,
      particularly in patients with NOTCH1/FBXW7 mutations. We screened samples from
      145 patients treated on the MRC UKALL2003 trial for PTEN mutations using
      heteroduplex analysis and gene deletions using single nucleotide polymorphism
      arrays, and related genotype to response to therapy and long-term outcome. PTEN
      loss-of-function mutations/gene deletions were detected in 22% (PTEN(ABN)).
      Quantification of mutant level indicated that 67% of mutated cases harbored more
      than one mutant, with up to four mutants detected, consistent with the presence
      of multiple leukemic sub-clones. Overall, 41% of PTEN(ABN) cases were considered
      to have biallelic abnormalities (mutation and/or deletion) with complete loss of
      PTEN in a proportion of cells. In addition, 9% of cases had N- or K-RAS
      mutations. Neither PTEN nor RAS genotype significantly impacted on response to
      therapy or long-term outcome, irrespective of mutant level, and there was no
      evidence that they changed the highly favorable outcome of patients with double
      NOTCH1/FBXW7 mutations. These results indicate that, for pediatric patients
      treated according to current protocols, routine screening for PTEN or RAS
      abnormalities at diagnosis is not warranted to further refine risk
      stratification. 

PMID- 26220043
TI  - Novel biomarkers for the identification and targeted therapy of gastric cancer.
AB  - Gastric cancer development follows the pathologic pattern such that chronic
      inflammation in the gastric mucosa progressively transforms normal mucosa into
      atrophy, intestinal metaplasia, adenoma/dysplasia and eventually invasive and
      metastatic tumors. The accumulation of multiple genetic and epigenetic
      alterations leads to the dysregulation of oncogenes and tumor suppressors, which
      was considered as the driver behind events during the tumorigenesis. Almost all
      gastric cancers are adenocarcinomas, which share considerable heterogeneity with
      distinct morphology, pathogenesis and clinical behavior. Therefore, identifying
      subtypes of gastric cancers with molecular and genetic features will be
      beneficial for the early identification and selection of new effective agents for
      targeted treatment. High-throughput sequencing techniques such as whole genomic,
      epigenome and transcriptome sequencing and proteomics platforms have identified
      major genomic characteristics that exhibit identification and prognostic impacts
      and distinct response patterns. In this article, the authors aim to summarize the
      information regarding the most promising molecules that may have clinical
      application as non-invasive biomarkers and therapy targets. 

PMID- 26220042
TI  - Cytoplasmic myosin-exposed apoptotic cells appear with caspase-3 activation and
      enhance CLL cell viability.
AB  - The degree of chronic lymphocytic leukemia (CLL) B-cell antigen receptor (BCR)
      binding to myosin-exposed apoptotic cells (MEACs) correlates with worse patient
      outcomes, suggesting a link to disease activity. Therefore, we studied MEAC
      formation and the effects of MEAC binding on CLL cells. In cell line studies,
      both intrinsic (spontaneous or camptothecin-induced) and extrinsic (FasL- or anti
      Fas-induced) apoptosis created a high percent of MEACs over time in a process
      associated with caspase-3 activation, leading to cytoplasmic myosin cleavage and
      trafficking to cell membranes. The involvement of common apoptosis pathways
      suggests that most cells can produce MEACs and indeed CLL cells themselves form
      MEACs. Consistent with the idea that MEAC formation may be a signal to remove
      dying cells, we found that natural IgM antibodies bind to MEACs. Functionally, co
      culture of MEACs with CLL cells, regardless of immunoglobulin heavy-chain
      variable region gene mutation status, improved leukemic cell viability. Based on
      inhibitor studies, this improved viability involved BCR signaling molecules.
      These results support the hypothesis that stimulation of CLL cells with antigen,
      such as those on MEACs, promotes CLL cell viability, which in turn could lead to
      progression to worse disease. 

PMID- 26220044
TI  - New advances in liver decellularization and recellularization: innovative and
      critical technologies.
AB  - Techniques for producing decellularized scaffolds for use in liver tissue
      engineering are emerging as promising methods for tissue reconstruction. In this
      article, the authors present an overview of liver decellularization methods
      developed and applied in recent years. These include the widespread use of
      various perfusion methods for the generation of a 3D scaffold, which may function
      as a template for either cell recellularization or direct biological application.
      The authors evaluate methods for scaffold production and explore some factors
      that may affect the decellularization process. In addition to tissue engineering,
      this overview includes a description of other potential applications for a
      decellularized liver scaffold. The authors also introduce the concept of
      fabrication of fragile biomaterial architecture and finally review the cell types
      applied to liver scaffold engineering.

PMID- 26220045
TI  - Minimally invasive liver surgery: an update.

PMID- 26220046
TI  - Oncological safety of ultrasound-guided laparoscopic liver resection for
      colorectal metastases: a case-control study.
AB  - Laparoscopic liver surgery has gained widespread acceptance and nowadays it is
      suggested even for malignant disease. Although the benefits on short-term
      outcomes have been proven, data on oncological safety are still lacking. The aim
      of this study is to assess oncologic results after ultrasound-guided laparoscopic
      liver resection (LLR) or open liver resection (OLR) for colorectal metastases. 37
      consecutive patients undergoing LLR between 01/2004 and 03/2014 were matched at a
      ratio of 1:1 with 37 OLR. Matching criteria were male sex, number and diameter of
      liver metastases, segment location, synchronous presentation, site and stage of
      primary tumor, positive lymph nodes of the primary, and concomitant extrahepatic
      disease. Demographic characteristics were similar among groups. Parenchymal
      transection time was longer in the LLR group (68 +/- 38.2 SD vs 40 +/- 33.7 SD, p
      = 0.01). Mortality was nil in LLR and OLR. Overall morbidity was significantly
      lower in LLR (13.5 vs 37.8%, p = 0.02), although severe complications were
      similar among the two groups. Patients undergoing LLR were discharged earlier (5
      +/- 2.3 SD vs 8 +/- 6.6 SD days, p < 0.001). The median margin width was 5 (0-40)
      mm in LLR vs 8 (0-25) mm in OLR, p = 0.897. R1 resection was recorded in four LLR
      and three OLR (p = 1). Overall recurrences were similar among groups. Eight
      patients with hepatic or extrahepatic recurrence among LLR underwent surgery vs
      four of OLR (p = 0.03). After a median follow-up of 35.7 months in LLR and 47.9
      months in OLR, 3-year overall survival was 91.8% LLR and 74.8% OLR (p = 0.14). 3
      year disease-free survival was 69.1% LLR and 65.9% OLR (p = 0.53). Multivariate
      analysis showed that postoperative complications [HR 3.42 (95% CI 1.32-8.89)] and
      multiple metastases [HR 3.84 (95% CI 1.34-10.83)] were independent predictors of
      worse survival (p = 0.01). Ultrasound-LLR for colorectal hepatic metastases is
      safe, ensuring oncologic outcomes comparable to OLR.

PMID- 26220047
TI  - Effects of cutting orientation in poplar wood biomass size reduction on enzymatic
      hydrolysis sugar yield.
AB  - The aim of this study was to understand how cutting orientation in poplar wood
      biomass size reduction affects enzymatic hydrolysis sugar yield of wood
      particles. A metal cutting (milling) machine was used to produce poplar wood
      particles from three cutting orientations. Results showed that cutting
      orientation significantly affected enzymatic hydrolysis sugar yield of wood
      particles. In this study, size reduction from the optimum cutting orientation
      produced 50% more sugars than the other two cutting orientations. Particles from
      the cutting orientation with the highest sugar yield had a large enzyme
      accessible area (125 mg orange dye/g biomass, as evaluated by Simons' stain
      procedure) and low crystallinity (50% crystallinity index, as calculated by the
      Segal method). Furthermore, small particle size did not necessarily lead to
      improvement in enzymatic digestibility.

PMID- 26220048
TI  - Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in
      patients with chronic heart failure.
AB  - BACKGROUND: Renal tubular damage (RTD) and hypoalbuminemia are risks for poor
      prognosis in patients with chronic heart failure (CHF). Renal tubules play a
      pivotal role in amino acid and albumin reabsorption, which maintain serum albumin
      levels. The aims of the present study were to (1) examine the association of RTD
      with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD
      and hypoalbuminemia in patients with CHF. METHODS AND RESULTS: We measured N
      acetyl-beta-D-glucosamidase (NAG) levels and the urinary beta2-microglobulin to
      creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR >= 300
      MUg/g or NAG >= 14.2 U/g. There were moderate correlations between RTD markers
      and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001).
      Multivariate logistic analysis showed that RTD was significantly related to
      hypoalbuminemia in patients with CHF. There were 134 cardiac events during a
      median period of 808 days. The comorbidity of RTD and hypoalbuminemia was
      increased with advancing New York Heart Association functional class.
      Multivariate Cox proportional hazard regression analysis showed that the presence
      of RTD and hypoalbuminemia was associated with cardiac events. The net
      reclassification index was significantly improved by adding RTD and
      hypoalbuminemia to the basic risk factors. CONCLUSION: Comorbid RTD and
      hypoalbuminemia are frequently observed and increase the risk for extremely poor
      outcome in patients with CHF.

PMID- 26220049
TI  - Dual-port laparoscopic abdominoperineal resection using the intended stoma site
      as the multichannel port.
AB  - We describe a novel minimally invasive procedure: dual-port laparoscopic
      abdominoperineal resection using a SILS port, and report our experience of using
      this to treat ten patients with lower rectal cancer. A SILS port was placed in
      the left lower quadrant at the intended colostomy site. A 5-mm trocar was
      inserted at the umbilicus at the subsequent drain site. Via a standard
      laparoscopic medial-to-lateral approach, the inferior mesenteric artery and vein
      were ligated and total mesorectal excision was performed. Via a perineal
      approach, the specimen was retrieved from the perineal wound, and a sigmoid
      colostomy was created at the site of the SILS port. Ten consecutive patients with
      lower rectal cancer at clinical stage T3 or lower underwent the procedure at our
      institution. The procedure was completed successfully in all patients, without
      any intraoperative problems and all postoperative outcomes were satisfactory.
      Thus, dual-port laparoscopic abdominoperineal resection can be performed safely
      and feasibly in selected patients.

PMID- 26220050
TI  - The potential of phototherapy to reduce body fat, insulin resistance and
      "metabolic inflexibility" related to obesity in women undergoing weight loss
      treatment.
AB  - BACKGROUND AND OBJECTIVE: The metabolic flexibility is often impaired in diseases
      associated with obesity, and many studies are based on the hypothesis that
      dysfunction in peripheral tissues such as skeletal muscle, liver and adipose
      tissue represent the etiology of development of metabolic inflexibility.
      Experimental evidence shows that the use of phototherapy combined with exercise
      was effective in controlling the lipid profile, reducing the mass of adipose
      tissue, suggesting increased metabolic activity and changes in lipid metabolism.
      However, we found few data in the literature involving the use of phototherapy in
      association to physical training in the obese population. Thus, our objective was
      to evaluate the effects of exercise training (aerobic plus resistance exercises)
      plus phototherapy (laser, 808 nm) on metabolic profile and adiponectinemia in
      obese women. STUDY DESIGN/MATERIALS AND METHODS: Sixty-four obese women (BMI 30
      40 kg/m2 , age between 20 and 40 years old) were randomly assigned in two groups:
      Exercise Training plus SHAM group (ET-SHAM, n = 32) and Exercise Training plus
      Phototherapy group (ET-PHOTO, n = 32). The treatment consisted in physical
      exercise intervention and the individual application of phototherapy immediately
      after the end of the training session. However, in the ET-SHAM group the device
      was turned off simulating the phototherapy application (placebo effect). The
      study protocol lasted for 20 weeks and comprised of three weekly sessions of
      aerobic plus resistance training and application of phototherapy (when
      applicable). The body composition and metabolic parameters were assessed (HOMA,
      adiponectin, insulin, glucose). RESULTS: Comparing the magnitude of effects
      between groups (ET-PHOTO vs. ET-SHAM), we observed that physical training plus
      phototherapy was more effective than physical training in reducing the delta of
      percentage of fat mass (%; -5.60 +/- 1.59 vs. -4.33 +/- 1.5; P < 0.04); fat mass
      (kg; -11.26 +/- 2.82 vs. -5.80 +/- 2.82; P < 0.0002); HOMA-IR index (-38.08 +/-
      9.23 vs. -20.91 +/- 14.42; P < 0.0001). In addition, we observed an increase in
      delta (%) of total skeletal muscle mass (kg; 0.60 +/- 1.09 vs. -1.38 +/- 1.70; P
      < 0.003), adiponectin concentration (ng/ml; 1.08 (0.04-3.62) vs. -0.42 (-3.15 to
      2.26); P < 0.03) in the same comparison. CONCLUSION: Our results demonstrated for
      the first time that phototherapy enhances the physical exercise effects in obese
      women undergoing weight loss treatment promoting significant changes in
      inflexibility metabolic profile.

PMID- 26220051
TI  - Core-decomposition-facilitated fabrication of hollow rare-earth silicate
      nanowalnuts from core-shell structures via the Kirkendall effect.
AB  - Hollow micro-/nanostructures have been widely applied in the fields of lithium
      ion batteries, catalysis, biosensing, biomedicine, and so forth. The Kirkendall
      effect, which involves a non-equilibrium mutual diffusion process, is one of many
      important fabrication strategies for the formation of hollow nanomaterials.
      Accordingly, full understanding of the interdiffusion process at the nanoscale is
      very important for the development of novel multifunctional hollow materials. In
      this work, hollow Y2SiO5 nanowalnuts have been fabricated from the conversion of
      YOHCO3@SiO2 core-shell nanospheres via the Kirkendall effect. More importantly,
      it was found that in the conversion process, the decomposition of YOHCO3 core
      imposes on the formation of the Y2SiO5 interlayer by facilitating the initial
      nucleation of the Kirkendall nanovoids and accelerating the interfacial diffusion
      of Y2O3@SiO2 core@shell. The simple concept developed herein can be employed as a
      general Kirkendall effect strategy without the assistance of any catalytically
      active Pt nanocrystals or gold motion for future fabrication of novel hollow
      nanostructures. Moreover, the photoluminescence properties of rare-earth ion
      doped hollow Y2SiO5 nanoparticles are researched. 

PMID- 26220053
TI  - From gas-phase to liquid-water chemical reactions: the fluorine atom plus water
      trimer system.
AB  - The potential energy profile for the F+(H2 O)3 ->HF+(H2 O)2 OH reaction has been
      investigated using the "gold standard" CCSD(T) method with correlation-consistent
      basis sets up to cc-pVQZ. Four different reaction pathways have been found and
      these are related, both geometrically and energetically. The entrance complexes
      F???(H2 O)3 for all four reaction pathways are found lying ca. 7 kcal mol(-1)
      below the separated reactants F+(H2 O)3 . The four reaction barriers on their
      respective reaction coordinates lie ca. 4 kcal mol(-1) below the reactants. There
      are also corresponding exit complexes HF???(H2 O)2 OH, lying about 13 kcal mol(
      1) below the separated products HF+(H2 O)2 OH. Compared with analogous F+(H2 O)2
      and F+H2 O reactions, the F+(H2 O)3 reaction is somewhat similar to the former
      but qualitatively different from the latter. It may be reasonable to predict that
      the reactions between atomic fluorine and water tetramer (or even larger water
      clusters) may be similar to the F+(H2 O)3 reaction. 

PMID- 26220052
TI  - A Highly Effective Ruthenium System for the Catalyzed Dehydrogenative Cyclization
      of Amine-Boranes to Cyclic Boranes under Mild Conditions.
AB  - We recently disclosed a new ruthenium-catalyzed dehydrogenative cyclization
      process (CDC) of diamine-monoboranes leading to cyclic diaminoboranes. In the
      present study, the CDC reaction has been successfully extended to a larger number
      of diamine-monoboranes (4-7) and to one amine-borane alcohol precursor (8). The
      corresponding NB(H)N- and NB(H)O-containing cyclic diaminoboranes (12-15) and
      oxazaborolidine (16) were obtained in good to high yields. Multiple substitution
      patterns on the starting amine-borane substrates were evaluated and the reaction
      was also performed with chiral substrates. Efforts have been spent to understand
      the mechanism of the ruthenium CDC process. In addition to a computational
      approach, a strategy enabling the kinetic discrimination on successive events of
      the catalytic process leading to the formation of the NB(H)N linkage was
      performed on the six-carbon chain diamine-monoborane 21 and completed with a (15)
      N NMR study. The long-life bis-sigma-borane ruthenium intermediate 23 possessing
      a reactive NHMe ending was characterized in situ and proved to catalyze the
      dehydrogenative cyclization of 1, ascertaining that bis sigma-borane ruthenium
      complexes are key intermediates in the CDC process. 

PMID- 26220055
TI  - Ice nucleation behaviour on sol-gel coatings with different surface energy and
      roughness.
AB  - In this paper, the ice nucleation temperatures of 10 MUL water droplets on a
      series of sol-gel coatings with different roughness and surface energies were
      obtained using a customized automatic measurement system. Classical nucleation
      theory was then employed to explain the different icing behaviour on the
      coatings. It was found that the wetting mode at low temperatures is strongly
      correlated with the icing behavior of the droplets on the surfaces. Ice-phobic
      coatings can lower the icing temperature of the droplet on the surface by up to
      6.9  degrees C compared with non-icephobic ones. Using classical nucleation
      theory, our results support some recent observations that the dominant nucleation
      sites are along the substrate-water-vapour three-phase contact line rather than
      at the substrate-water interface. 

PMID- 26220054
TI  - Dual plane diep flap inset: Optimizing esthetic outcome in delayed autologous
      breast reconstruction.
AB  - PURPOSE: In the present study, we compare the esthetic outcome in delayed
      autologous breast reconstruction, in the spectrum of irradiated chest wall,
      following two different abdominal flap inset. PATIENTS AND METHODS: Fifty women,
      candidates for microsurgical reconstruction with a free deep inferior epigastric
      perforator (DIEP) flap, participated in this prospective, randomized control
      study. In group-A (n = 25) the flap was inset using the traditional single plane
      in front of the pectoral muscle. In group-B (n = 25) the flap was inset in a dual
      plane lying simultaneously behind and in front of the pectoralis major at the
      upper and lower poles of the reconstructed breast, respectively. Photographic
      images were formulated to a PowerPoint presentation and cosmetic outcomes were
      assessed by means of a questionnaire and a visual analog scale. RESULTS: The dual
      plane flap inset presented significant advantages over the traditional single
      plane because of a better scarring (85.6 +/- 1.3 vs.73.6 +/- 1.2, P < 0.05),
      better transition from native and reconstructed tissues (90.2 +/- 1.5 vs. 81.5.6
      +/- 1.6, P < 0.05), better outline of the breast (96.3 +/- 1.2 vs. 69.6 +/- 2.1,
      P<0.0001), and better overal breast appearance (86 +/- 1.5 vs. 72.2 +/- 1.9, P <
      0.0001). Moreover, patient self-evaluation showed that dual plane reconstruction
      was associated with higher patient satisfaction without wearing brassiere (P =
      0.0016), and this could be attributed to the significantly greater fullness of
      the upper pole (P = 0.0015) and significantly less ptosis with time (P = 0.0014).
      CONCLUSION: The dual plane DIEP flap inset improves scar quality, advances the
      breast shape and fullness of the upper pole, and results in higher patient
      satisfaction.

PMID- 26220056
TI  - Au-iClick mirrors the mechanism of copper catalyzed azide-alkyne cycloaddition
      (CuAAC).
AB  - This report outlines the investigation of the iClick mechanism between gold(i)
      azides and gold(i)-acetylides to yield digold triazolates. Isolation of digold
      triazolate complexes offer compelling support for the role of two copper(i) ions
      in CuAAC. In addition, a kinetic investigation reveals the reaction is first
      order in both Au(i)-N3 and Au(i)-C[triple bond, length as m-dash]C-R, thus second
      order overall. A Hammett plot with a rho = 1.02(5) signifies electron-withdrawing
      groups accelerate the cycloaddition by facilitating the coordination of the
      second gold ion in a pi-complex. Rate inhibition by the addition of free
      triphenylphosphine to the reaction indicates that ligand dissociation is a
      prerequisite for the reaction. The mechanistic conclusions mirror those proposed
      for the CuAAC reaction. 

PMID- 26220058
TI  - Synthesis and conformational studies of chiral macrocyclic [1.1.1]metacyclophanes
      containing benzofuran rings.
AB  - Macrocyclic [1.1.1]metacyclophanes (MCPs) containing benzene and benzofuran rings
      linked by methylene bridges and which can be viewed as calixarene analogues, have
      been synthesized by demethylation of [3.3.1]MCP-diones with trimethylsilyl iodide
      (TMSI) in MeCN. The [3.3.1]MCP-diones are synthesized by using (p
      tolylsulfonyl)methyl isocyanide (TosMIC) as the cyclization reagent in N,N
      dimethylformamide (DMF) with an excess of sodium hydride. (1)H NMR spectroscopy
      revealed that the remaining hydroxyl group on the phenyl ring is involved in
      intramolecular hydrogen bonding with the oxygen of one of the benzofuran rings. O
      Methylation at the lower rim of monohydroxy[1.1.1]MCP in the presence of K2CO3 in
      acetone afforded a novel and inherently chiral calixarene analogue, namely the
      macrocyclic [1.1.1]MCP, possessing C1 symmetry. The inherent chirality of the two
      conformers was characterized by (1)H NMR spectroscopy by addition of an excess of
      Pirkle's chiral shift reagent, which caused a splitting of the corresponding
      methylene protons to AB patterns. Single crystal X-ray analysis revealed the
      adoptation of a hemisphere-shaped cone isomer. DFT calculations were carried out
      to investigate the energy-minimized structures and the hydrogen bonds of the
      synthesized MCPs. 

PMID- 26220057
TI  - Prolonged Suppression of Neuropathic Pain by Sequential Delivery of Lidocaine and
      Thalidomide Drugs Using PEGylated Graphene Oxide.
AB  - The management of patients with neuropathic pain is challenging. Monotherapy with
      a single pain relief drug may encounter different difficulties, such as short
      duration of efficacy and hence too many times of drug administration, and
      inadequate drug delivery. Recently, nanocarrier-based drug delivery systems have
      been proved to provide promising strategies for efficient drug loading, delivery,
      and release. In the present study, we developed poly(ethylene glycol) methyl
      ether functionalized graphene oxide (GO) bearing two commonly used drugs of
      lidocaine (LDC) and thalidomide (THD) as an agent for the treatment of
      neuropathic pain. The sequential drug release of LDC and THD from the developed
      LDC-THD-GO nanosheets exhibited a synergistic effect on neuropathic pain in vitro
      and in vivo, as evidenced by the increased pain threshold in mechanical allodynia
      and hyperalgesic response tests, and the improved inhibition of proinflammatory
      cytokines TNF-alpha, IL-1beta, IL-6, and nitric oxide. We believed that the
      present study herein would hold promise for future development of a new
      generation of potent agents for neuropathic pain relief.

PMID- 26220059
TI  - Trends in Utilization of Vocal Fold Injection Procedures.
AB  - Office-based vocal fold injections have become increasingly popular over the past
      15 years. Examination of trends in procedure coding for vocal fold injections in
      the United States from 2000 to 2012 was undertaken to see if they reflect this
      shift. The US Part B Medicare claims database was queried from 2000 through 2012
      for multiple Current Procedural Terminology codes. Over the period studied, the
      number of nonoperative laryngoscopic injections (31513, 31570) and operative
      medialization laryngoplasties (31588) remained constant. Operative vocal fold
      injection (31571) demonstrated marked linear growth over the 12-year study
      period, from 744 procedures in 2000 to 4788 in 2012-an increase >640%. The
      dramatic increased incidence in the use of code 31571 reflects an increasing
      share of vocal fold injections being performed in the operating room and not in
      an office setting, running counter to the prevailing trend toward awake, office
      based injection procedures. 

PMID- 26220061
TI  - New Age in Israel: Formative ethos, identity blindness, and implications for
      healthcare.
AB  - This article presents a critical analysis of New Age culture. We draw on two
      empirical studies conducted in Israel and show that the lofty notions about
      freedom from the shackles of socially structured identities and the unifying
      potential this holds, as well as the claim regarding the basic equality of human
      beings, are utopian. Blindness toward ethno-national identity reinforces
      identification with a self-evident hegemonic perception, thereby leading to the
      exclusion of peripheral groups such as indigenous populations. This exclusion is
      manifested in the discourse symbolically as well as in the praxis of
      complementary and alternative medicine, which is one of the main fields in which
      New Age culture is involved. Thus, the unifying ethos in the New Age culture
      becomes an illusionary paradise. This article contributes to the study of power
      relationships between New Age culture in diverse Western countries and the native
      and peripheral populations of these countries, and to the sociological study of
      complementary and alternative medicine incorporated into health organizations.

PMID- 26220060
TI  - The "HPV Discussion": Effective Use of Data to Deliver Recommendations to
      Patients Impacted by HPV.
AB  - OBJECTIVE: The dramatic rise in oropharyngeal squamous cell carcinoma associated
      with the human papilloma virus (HPV) has brought significant change to the
      interaction between patients and head and neck oncologists. HPV-induced cancers
      are generally the result of elements from the patient's sexual history, and
      otolaryngologists are generally less experienced than primary care physicians in
      addressing patient questions relating to sexual history and practices. This
      article addresses questions commonly posed by patients relating to HPV-induced
      head and neck cancers, issues related to HPV vaccination, and surveillance of HPV
      related lesions. Supporting data are provided such that physicians may be better
      equipped to sufficiently address patient queries on this topic. DATA SOURCES:
      Available peer-reviewed literature and clinical practice guidelines. REVIEW
      METHODS: Assessment and discussion of specific topics by authors selected from
      the Head and Neck Surgery Education Committee of the American Academy of
      Otolaryngology-Head and Neck Surgery Foundation. RESULTS: An educational
      "miniseminar" resulted in a notable increase in attendee knowledge and comfort
      regarding oropharyngeal squamous cell carcinoma counseling for patients in the
      setting of HPV-positive disease. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The
      dramatic increase in HPV-associated head and neck cancers has resulted in a
      changed paradigm of the physician-patient interaction. Care providers in today's
      environment must be prepared to counsel patients regarding sexually transmitted
      diseases and high-risk sexual behaviors. Examination of the existing data
      provides the foundation with which to construct a framework in which physicians
      can effectively communicate information and recommendations as they pertain to
      HPV-related carcinoma.

PMID- 26220062
TI  - Establishing credibility, constructing understanding: The epistemic struggle over
      healthy eating in the Finnish dietetic blogosphere.
AB  - What constitutes healthy eating is experiencing ongoing public debate, and this
      debate is increasingly taking place on the Internet. In this article, using a
      dialectical approach to analyse rhetorical discourse, we investigated how six
      highly popular Finnish nutrition counselling bloggers construct dietetic
      credibility and understanding. Their argumentation is compared to that of two
      academic experts contributing to the blog of the National Institute for Health
      and Welfare. Theoretically, we draw on Michael Billig's notions on how thinking
      and understanding are pervasively argumentative and reflect wider socio-cultural
      contexts, and on the dilemmatic nature of common sense. We demonstrate how the
      popular Finnish nutrition counselling bloggers rhetorically constructed a more
      particularistic and individualistic understanding of healthy eating in their
      argumentation in critical opposition to the universalistic and population-based
      understanding. In the popular Finnish nutrition counselling bloggers
      argumentation, practical, subjective and moral knowledge was valued, alongside
      abstract, scientific knowledge. In contrast, the National Institute for Health
      and Welfare bloggers typically utilised population-based averages and causalities
      in their argumentation. We argue that arguing over healthy eating in the public
      domain is fundamentally an epistemic struggle, in which different forms of
      knowledge and ways of knowing are valued, and dilemmas related to healthy eating
      are deliberated.

PMID- 26220063
TI  - Tuning Electronic Structure, Redox, and Photophysical Properties in Asymmetric
      NIR-Absorbing Organometallic BODIPYs.
AB  - Stepwise modification of the methyl groups at the alpha positions of BODIPY 1 was
      used for preparation of a series of mono- (2, 4, and 6) and diferrocene (3)
      substituted donor-acceptor dyads in which the organometallic substituents are
      fully conjugated with the BODIPY pi system. All donor-acceptor complexes have
      strong absorption in the NIR region and quenched steady-state fluorescence, which
      can be partially restored upon oxidation of organometallic group(s). X-ray
      crystallography of complexes 2-4 and 6 confirms the nearly coplanar arrangement
      of the ferrocene groups and the BODIPY pi system. Redox properties of the target
      systems were studied using cyclic voltammetry (CV) and differential pulse
      voltammetry (DPV). It was found that the first oxidation process in all dyads is
      ferrocene centered, while the separation between the first and the second
      ferrocene-centered oxidation potentials in diferrocenyl-containing dyad 3 is ~150
      mV. The density functional theory-polarized continuum model (DFT-PCM) and time
      dependent (TD) DFT-PCM methods were used to investigate the electronic structure
      as well as explain the UV-vis and redox properties of organometallic compounds 2
      4 and 6. TDDFT calculations allow for assignment of the charge-transfer and pi ->
      pi* transitions in the target compounds. The excited state dynamics of the parent
      BODIPY 1 and dyads 2-4 and 6 were investigated using time-resolved transient
      spectroscopy. In all organometallic dyads 2-4 and 6 the initially excited state
      is rapidly quenched by electron transfer from the ferrocene ligand. The lifetime
      of the charge-separated state was found to be between 136 and 260 ps and
      demonstrates a systematic dependence on the electronic structure and geometry of
      BODIPYs 2-4 and 6. 

PMID- 26220064
TI  - VHA Multiple Sclerosis Surveillance Registry and its similarities to other
      contemporary multiple sclerosis cohorts.
AB  - The Veterans Health Administration (VHA) has provided important contributions to
      our understanding of multiple sclerosis (MS); however, the characteristics of the
      modern VHA MS population have not been adequately characterized. Our objectives
      were to compare and contrast characteristics of the VHA MS population with other
      contemporary MS cohorts. A cross-sectional, mail-based survey of a stratified,
      random sample of 3,905 VHA users with MS was conducted. Detailed demographic and
      clinical data were collected as well as patient-reported outcomes assessing
      disability and quality of life. A total of 1,379 Veterans were enrolled into the
      MS Surveillance Registry (MSSR). Respondents did not differ from nonrespondents
      with regard to demographics or region. When compared to several other
      contemporary MS cohorts, some demographic differences were noted; however, the
      age of MS onset and diagnosis, subtype distribution, and most prevalent symptoms
      were very similar across MS cohorts. The MSSR appears to be representative of the
      general MS population. Combining the extensive VHA health services encounter data
      with the MSSR provides a rich and unique cohort for study. 

PMID- 26220065
TI  - Estimation of Values below the Limit of Detection of a Contemporary Sensitive
      Troponin I Assay Improves Diagnosis of Acute Myocardial Infarction.
AB  - BACKGROUND: The limit of detection (LoD) is the minimal amount of a substance
      that can be consistently detected. In the diagnosis of acute myocardial
      infarction (AMI) many patients present with troponin concentrations below the LoD
      of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored
      values below the LoD influence the diagnostic performance of these assays
      compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the
      impact of a new approach for interpolation of the left-censored data of a cs-cTnI
      assay in the evaluation of patients with suspected AMI. METHODS: Our posthoc
      analysis used a real world cohort of 1818 patients with suspected MI. Data on cs
      cTnI was available in 1786 patients. As a comparator the hs-cTnI version of the
      assay was used. To reconstruct quantities below the LoD of the cs-cTnI assay, a
      gamma regression approach incorporating the GRACE (Global Registry of Acute
      Coronary Events) score variables was used. RESULTS: Censoring of cs-cTnI data
      below the LoD yielded weaker diagnostic information [area under the curve (AUC),
      0.781; 95% CI, 0.731-0.831] regarding AMI compared to the hs-cTnI assay (AUC,
      0.949; CI, 0.936-0.961). Use of our model to estimate cs-cTnI values below the
      LoD showed an AUC improvement to 0.921 (CI, 0.902-0.940). The cs-cTnI LoD
      concentration had a negative predictive value (NPV) of 0.950. An estimated
      concentration that was to be undercut by 25% of patients presenting with
      suspected AMI was associated with an improvement of the NPV to 0.979.
      CONCLUSIONS: Estimation of values below the LoD of a cs-cTnI assay with this new
      approach improves the diagnostic performance in evaluation of patients with
      suspected AMI.

PMID- 26220067
TI  - Energy and temperature dependence of rigid unit modes in AlPO4-5.
AB  - For structures that can be treated as networks of rigid, corner-connected
      polyhedra, the dominant distortion modes can be described by so-called rigid unit
      modes that are close to zero frequency. This type of behaviour is common in
      zeolitic/zeotypic materials such as the AlPO4 family of compounds and has been
      suggested by some authors to play a significant role in molecular diffusion
      within the pores of such compounds. We explore the energy and temperature
      dependence of these modes in AlPO4-5 using inelastic neutron scattering and heat
      capacity measurements. Ab initio based computational modelling is also used to
      assign the observed dynamic behaviour to rigid unit modes. We observe that these
      rigid unit modes persist down to very low temperatures and show no signs of
      freezing out. 

PMID- 26220066
TI  - Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in
      Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab.
AB  - BACKGROUND: Biomarkers may play an important role in identifying patients at risk
      for cancer therapy cardiotoxicity. Our objectives were to define the patterns of
      change in biomarkers with cancer therapy and their associations with
      cardiotoxicity. METHODS: In a multicenter cohort of 78 breast cancer patients
      undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at
      baseline and every 3 months over a maximum follow-up of 15 months. These
      biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity,
      included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C
      reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP),
      growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental
      growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and
      galectin 3 (gal-3). We determined if biomarker increases were associated with
      cardiotoxicity at the same visit and the subsequent visit over the entire course
      of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation
      Criteria; alternative definitions were also considered. RESULTS: Across the
      entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases
      by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15
      months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at
      the same visit [MPO hazard ratio 1.38 (95% CI 1.10-1.71), P = 0.02; PlGF 3.78
      (1.30-11.0), P = 0.047; GDF-15 1.71 (1.15-2.55), P = 0.01] and the subsequent
      visit. MPO was robust to alternative outcome definitions. CONCLUSIONS: Increases
      in MPO are associated with cardiotoxicity over the entire course of doxorubicin
      and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value.
      These findings motivate validation studies in additional cohorts.

PMID- 26220068
TI  - In vitro effect of bergamot (Citrus bergamia) juice against cagA-positive and
      negative clinical isolates of Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori infection has been associated with chronic
      gastritis, peptic ulcer and gastric carcinoma as over half of the world's
      population is colonized with this gram-negative bacterium. Due to the increasing
      antibiotic resistance, its eradication rates fails in a great portion of
      patients. A number of studies showed that molecules largely distributed in
      commonly consumed fruits and vegetables may have antimicrobial activity. The aim
      of the present study was to investigate the effect of bergamot juice (BJ) against
      Helicobacter pylori in vitro. The potential therapeutic combination between BJ
      and the antibiotics amoxicillin (AMX), clarithromycin (CLA) and metronidazole
      (MTZ) has also been evaluated. METHODS: The minimum inhibitory concentration
      (MIC) of BJ, AMX, CLA and MTZ against 2 ATCC and 32 clinical isolates of H.
      pylori was assayed according to CLSI. The checkerboard method was used to
      determine the efficacy of the association BJ with the three reference
      antibiotics. Killing curves were performed on the two cagA-positive ATCC strains
      of H. pylori (ATCC 43504 and ATCC 49503), on the clinical isolate cagA-positive
      HP6 strain of H. pylori and on the clinical isolate cagA-negative HP61 strain of
      H. pylori. RESULTS: BJ (2.5%, v/v) inhibited the growth of 50% of the H. pylori
      clinical isolates, whereas 5% (v/v) inhibited 90%. AMX was the most effective
      antibiotic against the reference strains and the clinical isolates, followed by
      CLA and MTZ. In the combination assays, synergism was observed between BJ and AMX
      and between BJ and MTZ against both the reference strains and the clinical
      isolates. Indifference was observed between BJ and CLA. CONCLUSIONS: BJ was
      effective in vitro against H. pylori and the genotype status of the clinical
      strains may have an impact on its susceptibility. The synergistic combination of
      BJ and antibiotics could be used to prevent or treat resistance.

PMID- 26220069
TI  - Optimal Antibiotic Dosage for Chronic Kidney Disease Patient: A Pharmacological
      Manual for Oral Clinicians.
AB  - Chronic kidney disease, (CKD) a gradual and inevitable deterioration in renal
      function, is the disease with the most associations in dentistry. Dosage
      adjustment is one amongst the vital elements to be familiar with during their
      oral care. CKD patients take extended duration to filter out medications,
      therefore dosage must always be tailored under the supervision of nephrologist.
      The relished benefits from antibiotic could transform as anti-microbial
      resistance on their abuse and nephrotoxic when contraindicated drugs are
      encouraged. New patented drug belonging to oxazoliodine group has driven the
      researchers to handle the emerging AMR. The present communication discusses the
      pharmacological factors influencing in prescribing the antibiotics for CKD
      patient from the dentist's point of view. The formulas destined for calculating
      the optimal dosage of antibiotics have been documented to aid oral physicians. 

PMID- 26220071
TI  - Improving hand hygiene in hospitals--more is better.

PMID- 26220072
TI  - Let's raise a glass to the ordinary sensible patient.

PMID- 26220070
TI  - Comparative efficacy of interventions to promote hand hygiene in hospital:
      systematic review and network meta-analysis.
AB  - OBJECTIVE: To evaluate the relative efficacy of the World Health Organization
      2005 campaign (WHO-5) and other interventions to promote hand hygiene among
      healthcare workers in hospital settings and to summarize associated information
      on use of resources. DESIGN: Systematic review and network meta-analysis. DATA
      SOURCES: Medline, Embase, CINAHL, NHS Economic Evaluation Database, NHS Centre
      for Reviews and Dissemination, Cochrane Library, and the EPOC register (December
      2009 to February 2014); studies selected by the same search terms in previous
      systematic reviews (1980-2009). REVIEW METHODS: Included studies were randomised
      controlled trials, non-randomised trials, controlled before-after trials, and
      interrupted time series studies implementing an intervention to improve
      compliance with hand hygiene among healthcare workers in hospital settings and
      measuring compliance or appropriate proxies that met predefined quality inclusion
      criteria. When studies had not used appropriate analytical methods, primary data
      were re-analysed. Random effects and network meta-analyses were performed on
      studies reporting directly observed compliance with hand hygiene when they were
      considered sufficiently homogeneous with regard to interventions and
      participants. Information on resources required for interventions was extracted
      and graded into three levels. RESULTS: Of 3639 studies retrieved, 41 met the
      inclusion criteria (six randomised controlled trials, 32 interrupted time series,
      one non-randomised trial, and two controlled before-after studies). Meta-analysis
      of two randomised controlled trials showed the addition of goal setting to WHO-5
      was associated with improved compliance (pooled odds ratio 1.35, 95% confidence
      interval 1.04 to 1.76; I(2)=81%). Of 22 pairwise comparisons from interrupted
      time series, 18 showed stepwise increases in compliance with hand hygiene, and
      all but four showed a trend for increasing compliance after the intervention.
      Network meta-analysis indicated considerable uncertainty in the relative
      effectiveness of interventions, but nonetheless provided evidence that WHO-5 is
      effective and that compliance can be further improved by adding interventions
      including goal setting, reward incentives, and accountability. Nineteen studies
      reported clinical outcomes; data from these were consistent with clinically
      important reductions in rates of infection resulting from improved hand hygiene
      for some but not all important hospital pathogens. Reported costs of
      interventions ranged from $225 to $4669 (L146-L3035; ?204-?4229) per 1000 bed
      days. CONCLUSION: Promotion of hand hygiene with WHO-5 is effective at increasing
      compliance in healthcare workers. Addition of goal setting, reward incentives,
      and accountability strategies can lead to further improvements. Reporting of
      resources required for such interventions remains inadequate.

PMID- 26220073
TI  - Emotional motivators might improve hand hygiene among healthcare workers.

PMID- 26220074
TI  - Variability of vertical ground reaction forces collected with one and two force
      plates in healthy dogs.
AB  - OBJECTIVE: To compare peak vertical force (PVF) and vertical impulse (VI) data
      collected with one and two force plates during the same collection time period in
      healthy dogs at a trot. ANIMALS: Seventeen healthy client-owned adult dogs.
      METHODS: Vertical ground reaction force (GRF) data were collected in a crossover
      study design, with four sessions on two consecutive days, and then two weeks
      apart (days 1, 2, 15, and 16) using both one and two force plates collection
      methods. A repeated measures model analysis of variance (ANOVA) was used to test
      for differences in force plate PVF, VI, and average time per trial (ATT) between
      days, weeks, and systems (1 plate versus 2 plates). Coefficients of variation for
      PVF and VI were also calculated separately by forelimbs and hindlimbs, plates,
      day, and week. RESULTS: The time required to obtain a valid trial was
      significantly longer using a single force plate when compared with two force
      plates. Comparing GRF data for all dogs, significant differences in PVF data were
      found between one and two force plates, however, these differences were
      diminutive in absolute magnitude, and of unknown clinical importance. Examination
      of the coefficients of variation for PVF and VI during the different collection
      periods yielded similar results. CONCLUSIONS: Use of two force plates decreased
      trial repetition and collection time. Vertical GRF data had a similar coefficient
      of variation with either one or two force plates collection techniques in healthy
      dogs.

PMID- 26220075
TI  - Rapid and Sensitive Detection of Vibrio alginolyticus by Loop-Mediated Isothermal
      Amplification Combined with a Lateral Flow Dipstick Targeted to the rpoX Gene.
AB  - Vibrio alginolyticus is a major bacterial pathogen causing disease in marine
      animals. The present study aimed to develop a loop-mediated isothermal
      amplification (LAMP) coupled with a lateral flow dipstick (LFD) for rapid and
      simple visual detection of V. alginolyticus-specific amplicons. The biotin
      labeled LAMP amplicons from the targeted portion of a gene encoding rpoS-like
      sigma factor (rpoX) were generated at 60 degrees C for 1 h and then hybridized
      with a fluorescein isothiocyanate-labeled probe for 5 min for visual detection
      with LFD. In pure cultures, the detection limit of the LAMP-LFD technique for V.
      alginolyticus was 1.8 * 10(2) CFU/mL while that of PCR was 1.8 * 10(3) CFU/mL. In
      spiked whiteleg shrimp samples Penaeus vannamei, the sensitivity for V.
      alginolyticus detection was 2 * 10(3) CFU/g (equivalent to 4 CFU per reaction)
      while PCR was 10 times less sensitive. The LAMP-LFD method for V. alginolyticus
      correctly identified 21 isolates of V. alginolyticus but did not recognize 23 non
      V. alginolyticus Vibrio isolates and 15 non-Vibrio isolates. In summary, this
      LAMP-LFD method targeted to the rpoX gene is a convenient assay for specific
      identification of V. alginolyticus with high sensitivity.

PMID- 26220076
TI  - Taxonomic description and genome sequence of Rheinheimera mesophila sp. nov.,
      isolated from an industrial waste site.
AB  - A novel Gram-staining-negative gammaproteobacterium, designated IITR-13T, was
      isolated from a pesticide-contaminated soil and characterized using a polyphasic
      approach. On the basis of 16S rRNA gene sequence analysis, the strain showed the
      closest similarity (98.7 %) to Rheinheimera tangshanensis JA3-B52T followed by
      Rheinheimera texasensis A62-14BT (97.7 %) and Rheinheimera soli BD-d46T (97.3 %).
      The 16S rRNA gene sequence similarity of the novel strain to other members of the
      genus Rheinheimera was < 97.3 %. However, DNA-DNA hybridization between strain
      IITR-13T and the type strains of R. tangshanensis, R. texasensis and R. soli was
      47.5 +/- 0.6, 42.4 +/- 0.4 and 39.8 +/- 0.3 %, respectively; these values are
      less than 70 %, a threshold value for delineation of a novel species. The strain
      had C12 : 0 3-OH, C16 : 0, C17 : 1omega8c, summed feature 3 (C16 : 1omega6c/C16 :
      1omega7c) and C18 : 1omega6c as the major fatty acids. The major isoprenoid
      quinones detected for strain IITR-13T were ubiquinone Q-8 and menaquinone MK
      7.The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylinositol and seven unknown phospholipids. Based on phenotypic and
      chemotaxonomic characteristics and analysis of the 16S rRNA gene sequence, the
      novel strain should be assigned to a novel species, for which the name
      Rheinheimera mesophila sp. nov. is proposed, with the type strain IITR-13T ( =
      MTCC 12064T = DSM 29723T). Also, we report the draft genome sequence of
      Rheinheimera mesophila IITR-13T; the draft genome sequence includes 3 749 903
      bases and comprises 3449 predicted coding sequences, with a G+C content of 47.8
      %. It consists of 102 contigs (>1000 bp). 

PMID- 26220077
TI  - DNA-Segment-Facilitated Dissociation of Fis and NHP6A from DNA Detected via
      Single-Molecule Mechanical Response.
AB  - The rate of dissociation of a DNA-protein complex is often considered to be a
      property of that complex, without dependence on other nearby molecules in
      solution. We study the kinetics of dissociation of the abundant Escherichia coli
      nucleoid protein Fis from DNA, using a single-molecule mechanics assay. The rate
      of Fis dissociation from DNA is strongly dependent on the solution concentration
      of DNA. The off-rate (k(off)) of Fis from DNA shows an initially linear
      dependence on solution DNA concentration, characterized by an exchange rate of
      k(ex)~9*10(-4) (ng/MUl)(-1) s(-1) for 100 mM univalent salt buffer, with a very
      small off-rate at zero DNA concentration. The off-rate saturates at approximately
      k(off,max)~8*10(-3) s(-1) for DNA concentrations above ~20 ng/MUl. This exchange
      reaction depends mainly on DNA concentration with little dependence on the length
      of the DNA molecules in solution or on binding affinity, but this does increase
      with increasing salt concentration. We also show data for the yeast HMGB protein
      NHP6A showing a similar DNA-concentration-dependent dissociation effect, with
      faster rates suggesting generally weaker DNA binding by NHP6A relative to Fis.
      Our results are well described by a model with an intermediate partially
      dissociated state where the protein is susceptible to being captured by a second
      DNA segment, in the manner of "direct transfer" reactions studied for other DNA
      binding proteins. This type of dissociation pathway may be important to protein
      DNA binding kinetics in vivo where DNA concentrations are large.

PMID- 26220078
TI  - Reconstruction of metastatic acetabular defects using a modified Harrington
      procedure.
AB  - BACKGROUND AND PURPOSE: Metastases engaging the acetabulum result in significant
      disability. We investigated the outcome after curettage and reconstruction of the
      defect with a protrusio cage, retrograde screws, and a cemented total hip
      arthroplasty. PATIENTS AND METHODS: We retrospectively identified 70 consecutive
      patients who were surgically treated for metastatic disease of the acetabulum
      between 1995 and 2012 using the above technique. The type of primary tumor,
      extent of the disease, degree of acetabular erosion, and type of implant used
      were identified. Patient and implant survival, complications, and functional
      outcome were recorded. RESULTS: There were no mortalities in the perioperative
      period (30 days after surgery). Median overall patient survival was 12 months.
      Prosthesis survival was 92% at 1 year and 89% at 5 years. One third of the
      patients suffered a complication, the most frequent one being dislocation. The
      functional outcome was good. Multiple skeletal or visceral metastases and
      specific types of cancer were associated with poor patient survival.
      INTERPRETATION: Reconstruction of metastatic acetabular defects using a protrusio
      cage stabilized with retrograde screws and a cemented total hip arthroplasty is a
      safe procedure that provides efficient relief of symptoms. Patients with
      extensive disease, especially when diagnosed with specific types of cancer, have
      a very poor prognosis. The complication rate is substantial, the most frequent
      being dislocation. However, revision surgery is seldom required and prosthesis
      survival is high.

PMID- 26220079
TI  - Combined therapy for multi-drug-resistant Acinetobacter baumannii infection--is
      there evidence outside the laboratory?
AB  - Acinetobacter are among the most common bacteria isolated in hospital infections,
      especially in developing countries. Multi-drug, extended-drug or pan-drug
      resistance makes treatment a real medical challenge. In the present review, the
      authors describe clinical and experimental data in order to present different
      current and potential future strategies to treat infections caused by multi-drug
      resistant Acinetobacter. The therapeutic options for carbapenem-resistant
      Acinetobacter are scarce, and the current options have poor pharmacokinetic
      aspects and several side effects. Combined therapy has been an alternative for
      multi-drug-resistant Acinetobacter. However, this issue is always controversial.
      In some studies combined therapy has shown superiority for some strains of
      Acinetobacter in animal models and in vitro studies. However, studies with humans
      are scarce and too poor quality to suggest the best approach for the treatment of
      infections caused by multi-drug-resistant Acinetobacter baumannii. 

PMID- 26220080
TI  - Treatment challenges for urogenital and anorectal Chlamydia trachomatis.
AB  - While true antimicrobial resistance to Chlamydia trachomatis is a rare
      occurrence, repeat chlamydia infections continue to be reported following
      treatment with a single 1 g dose of azithromycin or week long doxycycline - with
      considerable more concern about azithromycin treatment failure. While most repeat
      positive cases are likely to be reinfections, emerging evidence indicates
      treatment failure may play a role. Current data suggests that there may are
      differences in the efficacy of the drugs between rectal and non-rectal sites of
      infection and factors such as immune response, drug pharmacokinetics, organism
      load, auto-inoculation from rectum to cervix in women and the genital microbiome
      may play a role in treatment failure. Other possible reasons for repeat infection
      include the low discriminatory power of NAAT tests to differentiate between
      viable and nonviable organisms and failure to detect LGV infection. This review
      will present the current evidence regarding the management challenges for
      urogenital and anorectal chlamydia infections and provide some suggestions for
      where future research efforts are needed to address important knowledge gaps in
      this area and provide stronger evidence for the development of robust treatment
      guidelines.

PMID- 26220081
TI  - A Comparison of Intravenous plus Intraperitoneal Chemotherapy with Intravenous
      Chemotherapy Alone for the Treatment of Gastric Cancer: A Meta-Analysis.
AB  - We aimed to evaluate the effectiveness and safety of intravenous (IV) plus
      intraperitoneal (IP) chemotherapy compared to intravenous (IV) chemotherapy alone
      for patients with gastric cancer. Electronic databases were searched up to June
      2013. Two authors independently selected studies, extracted data and assessed the
      quality of included studies. The GRADE System was adopted to rate the level of
      evidence. Of 392 citations, five RCTs involving 1072 patients were included.
      Overall, a significant improvement in in one- and three- and five-year survival
      rate was observed in the IV plus IP chemotherapy group (3 RCTs, n = 360, RR =
      1.10, 95% CI 1.04 to 1.17), (5 RCTs, n = 953, RR = 1.22, 95% CI 1.11 to 1.35) and
      (3 RCTs, n = 347, RR = 1.42, 95% CI 1.12 to 1.80), respectively. Results
      supported a significant decrease in the rate of metastases (1 RCT, n = 85, RR =
      0.41 95% CI 0.19 to 0.89) and peritoneal recurrence (2 RCTs, n = 297, RR = 0.41,
      95% CI 0.26 to 0.62) in the IV plus IP chemotherapy group, however, the incidence
      of adverse events was increased. For patients with gastric cancer, IV plus IP
      chemotherapy can improve the overall survival rate and prevent the distant or
      peritoneal metastases. An increased risk of neutropenia, peripheral edema and
      neuropathy was observed.

PMID- 26220082
TI  - Constitutive overexpression of the TaNF-YB4 gene in transgenic wheat
      significantly improves grain yield.
AB  - Heterotrimeric nuclear factors Y (NF-Ys) are involved in regulation of various
      vital functions in all eukaryotic organisms. Although a number of NF-Y subunits
      have been characterized in model plants, only a few have been functionally
      evaluated in crops. In this work, a number of genes encoding NF-YB and NF-YC
      subunits were isolated from drought-tolerant wheat (Triticum aestivum L. cv.
      RAC875), and the impact of the overexpression of TaNF-YB4 in the Australian wheat
      cultivar Gladius was investigated. TaNF-YB4 was isolated as a result of two
      consecutive yeast two-hybrid (Y2H) screens, where ZmNF-YB2a was used as a
      starting bait. A new NF-YC subunit, designated TaNF-YC15, was isolated in the
      first Y2H screen and used as bait in a second screen, which identified two wheat
      NF-YB subunits, TaNF-YB2 and TaNF-YB4. Three-dimensional modelling of a TaNF
      YB2/TaNF-YC15 dimer revealed structural determinants that may underlie
      interaction selectivity. The TaNF-YB4 gene was placed under the control of the
      strong constitutive polyubiquitin promoter from maize and introduced into wheat
      by biolistic bombardment. The growth and yield components of several independent
      transgenic lines with up-regulated levels of TaNF-YB4 were evaluated under well
      watered conditions (T1-T3 generations) and under mild drought (T2 generation).
      Analysis of T2 plants was performed in large deep containers in conditions close
      to field trials. Under optimal watering conditions, transgenic wheat plants
      produced significantly more spikes but other yield components did not change.
      This resulted in a 20-30% increased grain yield compared with untransformed
      control plants. Under water-limited conditions transgenic lines maintained parity
      in yield performance. 

PMID- 26220083
TI  - The wheat AGC kinase TaAGC1 is a positive contributor to host resistance to the
      necrotrophic pathogen Rhizoctonia cerealis.
AB  - Considerable progress has been made in understanding the roles of AGC kinases in
      mammalian systems. However, very little is known about the roles of AGC kinases
      in wheat (Triticum aestivum). The necrotrophic fungus Rhizoctonia cerealis is the
      major pathogen of the destructive disease sharp eyespot of wheat. In this study,
      the wheat AGC kinase gene TaAGC1, responding to R. cerealis infection, was
      isolated, and its properties and role in wheat defence were characterized. R.
      cerealis-resistant wheat lines expressed TaAGC1 at higher levels than susceptible
      wheat lines. Sequence and phylogenetic analyses showed that the TaAGC1 protein is
      a serine/threonine kinase belonging to the NDR (nuclear Dbf2-related) subgroup of
      AGC kinases. Kinase activity assays proved that TaAGC1 is a functional kinase and
      the Asp-239 residue located in the conserved serine/threonine kinase domain of
      TaAGC1 is required for the kinase activity. Subcellular localization assays
      indicated that TaAGC1 localized in the cytoplasm and nucleus. Virus-induced
      TaAGC1 silencing revealed that the down-regulation of TaAGC1 transcripts
      significantly impaired wheat resistance to R. cerealis. The molecular
      characterization and responses of TaAGC1 overexpressing transgenic wheat plants
      indicated that TaAGC1 overexpression significantly enhanced resistance to sharp
      eyespot and reduced the accumulation of reactive oxygen species (ROS) in wheat
      plants challenged with R. cerealis. Furthermore, ROS-scavenging and certain
      defence-associated genes were up-regulated in resistant plants overexpressing
      TaAGC1 but down-regulated in susceptible knock-down plants. These results
      suggested that the kinase TaAGC1 positively contributes to wheat immunity to R.
      cerealis through regulating expression of ROS-related and defence-associated
      genes. 

PMID- 26220084
TI  - Genome investigation suggests MdSHN3, an APETALA2-domain transcription factor
      gene, to be a positive regulator of apple fruit cuticle formation and an
      inhibitor of russet development.
AB  - The outer epidermal layer of apple fruit is covered by a protective cuticle.
      Composed of a polymerized cutin matrix embedded with waxes, the cuticle is a
      natural waterproof barrier and protects against several abiotic and biotic
      stresses. In terms of apple production, the cuticle is essential to maintain long
      post-harvest storage, while severe failure of the cuticle can result in the
      formation of a disorder known as russet. Apple russet results from micro-cracking
      of the cuticle and the formation of a corky suberized layer. This is typically an
      undesirable consumer trait, and negatively impacts the post-harvest storage of
      apples. In order to identify genetic factors controlling cuticle biosynthesis
      (and thus preventing russet) in apple, a quantitative trait locus (QTL) mapping
      survey was performed on a full-sib population. Two genomic regions located on
      chromosomes 2 and 15 that could be associated with russeting were identified.
      Apples with compromised cuticles were identified through a novel and high
      throughput tensile analysis of the skin, while histological analysis confirmed
      cuticle failure in a subset of the progeny. Additional genomic investigation of
      the determined QTL regions identified a set of underlying genes involved in
      cuticle biosynthesis. Candidate gene expression profiling by quantitative real
      time PCR on a subset of the progeny highlighted the specific expression pattern
      of a SHN1/WIN1 transcription factor gene (termed MdSHN3) on chromosome 15.
      Orthologues of SHN1/WIN1 have been previously shown to regulate cuticle formation
      in Arabidopsis, tomato, and barley. The MdSHN3 transcription factor gene
      displayed extremely low expression in lines with improper cuticle formation,
      suggesting it to be a fundamental regulator of cuticle biosynthesis in apple
      fruit. 

PMID- 26220085
TI  - G-fibre cell wall development in willow stems during tension wood induction.
AB  - Willows (Salix spp.) are important as a potential feedstock for bioenergy and
      biofuels. Previous work suggested that reaction wood (RW) formation could be a
      desirable trait for biofuel production in willows as it is associated with
      increased glucose yields, but willow RW has not been characterized for cell wall
      components. Fasciclin-like arabinogalactan (FLA) proteins are highly up-regulated
      in RW of poplars and are considered to be involved in cell adhesion and cellulose
      biosynthesis. COBRA genes are involved in anisotropic cell expansion by
      modulating the orientation of cellulose microfibril deposition. This study
      determined the temporal and spatial deposition of non-cellulosic polysaccharides
      in cell walls of the tension wood (TW) component of willow RW and compared it
      with opposite wood (OW) and normal wood (NW) using specific antibodies and
      confocal laser scanning microscopy and transmission electron microscopy. In
      addition, the expression patterns of an FLA gene (SxFLA12) and a COBRA-like gene
      (SxCOBL4) were compared using RNA in situ hybridization. Deposition of the non
      cellulosic polysaccharides (1-4)-beta-D-galactan, mannan and de-esterified
      homogalacturonan was found to be highly associated with TW, often with the G
      layer itself. Of particular interest was that the G-layer itself can be highly
      enriched in (1-4)-beta-D-galactan, especially in G-fibres where the G-layer is
      still thickening, which contrasts with previous studies in poplar. Only xylan
      showed a similar distribution in TW, OW, and NW, being restricted to the
      secondary cell wall layers. SxFLA12 and SxCOBL4 transcripts were specifically
      expressed in developing TW, confirming their importance. A model of
      polysaccharides distribution in developing willow G-fibre cells is presented. 

PMID- 26220086
TI  - Activated regulatory T cells suppress effector NK cell responses by an IL-2
      mediated mechanism during an acute retroviral infection.
AB  - BACKGROUND: It is well established that effector T cell responses are crucial for
      the control of most virus infections, but they are often tightly controlled by
      regulatory T cells (Treg) to minimize immunopathology. NK cells also contribute
      to virus control but it is not known if their antiviral effect is influenced by
      virus-induced Tregs as well. We therefore analyzed whether antiretroviral NK cell
      functions are inhibited by Tregs during an acute Friend retrovirus infection of
      mice. RESULTS: Selective depletion of Tregs by using the transgenic DEREG mouse
      model resulted in improved NK cell proliferation, maturation and effector cell
      differentiation. Suppression of NK cell functions depended on IL-2 consumption by
      Tregs, which could be overcome by specific NK cell stimulation with an IL-2/anti
      IL-2 mAb complex. CONCLUSIONS: The current study demonstrates that virus-induced
      Tregs indeed inhibit antiviral NK cell responses and describes a targeted
      immunotherapy that can abrogate the suppression of NK cells by Tregs.

PMID- 26220088
TI  - Arg753Gln Polymorphisms in Toll-Like Receptor 2 Gene are Associated with
      Tuberculosis Risk: A Meta-Analysis.
AB  - BACKGROUND: Numerous epidemiological studies have reported the association
      between polymorphisms of Toll-like receptor 2 (TLR2) and susceptibility to
      tuberculosis (TB). However, the results remain inconclusive. Therefore, we
      performed a quantitative meta-analysis to evaluate associations between the
      polymorphism of Arg753Gln of the TLR2 gene and susceptibility to TB. MATERIAL AND
      METHODS: Three databases (PubMed, CNKI and Embase) were systematically searched
      for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals
      (CIs) as our index were used to assess the relation between the TLR2 gene
      Arg753Gln polymorphism and risk of TB. Overall and subgroup analyses were
      conducted according to the available information. RESULTS: With a detailed
      selection, 7 eligible studies with 1486 cases and 1322 controls were identified
      in our meta-analysis. There was a significant difference between TLR2 gene
      Arg753Gln polymorphism and the risk of TB (additive model: P<0.01, OR=2.89, 95%
      CI: 2.13-3.91; GA vs. GG: P<0.01, OR=2.92, 95% CI: 2.09-4.08). Interestingly,
      subgroup analysis based on ethnicity indicated that TB risk was significantly
      increased in Asians (additive model: P<0.01, OR=3.17, 95% CI: 2.31-4.35; GA vs.
      GG: P<0.01, OR=3.29, 95% CI: 2.32-4.68); by contrast, there was no association
      found in whites (additive model: P=0.40, OR=0.57, 95% CI: 0.15-2.13; GA vs. GG:
      P=0.40, OR=0.57, 95% CI: 0.15-2.13). CONCLUSIONS: Our meta-analysis provides
      evidence that the TLR2 gene Arg753Gln polymorphism is a risk factor to TB,
      especially in Asian populations.

PMID- 26220087
TI  - Downregulation of dystroglycan glycosyltransferases LARGE2 and ISPD associate
      with increased mortality in clear cell renal cell carcinoma.
AB  - BACKGROUND: Dystroglycan (DG) is a cell-surface laminin receptor that links the
      cytoskeleton to the extracellular matrix in a variety of epithelial tissues. Its
      function as a matrix receptor requires extensive glycosylation of its
      extracellular subunit alphaDG, which involves at least 13 distinct genes. Prior
      work has shown loss of alphaDG glycosylation in an assortment of carcinomas,
      including clear cell renal cell carcinoma (ccRCC) though the cause (s) and
      functional consequences of this loss are still unclear. METHODS: Using The Cancer
      Genome Atlas (TCGA) database, we analyzed the DG glycosylation pathway to
      identify changes in mRNA expression and correlation with clinical outcomes. We
      validated our findings with a cohort of 65 patients treated with radical
      nephrectomy by analyzing DG glycosylation via immunohistochemistry and gene
      expression via qRT-PCR. RESULTS: Analysis of TCGA database revealed frequent
      dysregulation of a subset of DG glycosyltransferases. Most notably, there was a
      frequent, significant downregulation of GYLTL1B (LARGE2) and ISPD. DG
      glycosylation is frequently impaired in ccRCC patient samples and most strongly
      associates with downregulation of GYLTL1B. CONCLUSIONS: Reduced levels of GYLTL1B
      and ISPD mRNA associated with increased patient mortality and are the likely
      cause of alphaDG hypoglycosylation in ccRCC.

PMID- 26220089
TI  - Short-term intensive psychodynamic group therapy versus cognitive-behavioral
      group therapy in day treatment of anxiety disorders and comorbid depressive or
      personality disorders: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Psychodynamic and cognitive-behavioral group therapies are frequently
      applied in day hospitals for the treatment of anxiety disorders and comorbid
      depressive or personality disorders in Poland and other Eastern European
      countries. Yet there is not enough evidence as to their effectiveness in this
      environment; this study addresses this gap. The aim of the study is to determine
      the effectiveness of these two kinds of day treatment care consisting of
      intensive, short-term group psychodynamic and cognitive-behavioral therapy, for
      patients with anxiety disorders and/or comorbid depressive or personality
      disorders. Our objectives are to: 1) show the effectiveness of each treatment in
      a day-care setting relative to the wait-list control group; 2) demonstrate the
      relative short- and long-term effectiveness of the two active treatments; 3)
      carry out a preliminary examination of the predictors and moderators of treatment
      response; 4) carry out a preliminary examination of the mediators of therapeutic
      change; and 5) compare the impact of both methods of treatment on the outcome of
      the measures used in this study. METHODS/DESIGN: In this randomized controlled
      trial, a total of 199 patients with anxiety disorders and comorbid depressive
      and/or personality disorders will be assigned to one of three conditions: 1)
      psychodynamic group therapy; 2) cognitive-behavioral group therapy; or 3) wait
      list control group. The therapy will last 12 weeks. Both treatments will be
      manualized (the manuals will address comorbidity). Primary outcome measures will
      include self-reported symptoms of anxiety, observer-rated symptoms of anxiety,
      global improvement, and recovery rate. Secondary outcome measures will include
      the number of pathological personality traits, depression, self-esteem, defense
      mechanisms, beliefs about self and others, interpersonal problems, object
      relations, parental bonding, meta-cognition, and quality of life. Measures will
      be taken at baseline, post-treatment, and at six months following the end of
      therapy. DISCUSSION: The rationale is to investigate how effectively anxiety
      disorders and/or comorbid depressive or personality disorders can be treated in a
      day hospital setting, typical of the Polish health care system, during a three
      month treatment period. TRIAL REGISTRATION: Clinicaltrials.gov identifier
      NCT02126787 , registered on 28 April 2014.

PMID- 26220090
TI  - Development of HIV-1 integrase inhibitors: recent molecular modeling
      perspectives.
AB  - Of the three viral enzymes essential to HIV replication, HIV-1 integrase (IN) is
      gaining popularity as a target for the antiviral therapy of AIDS. Substantial
      work focusing on IN has been done over the past three decades, which has
      facilitated and led to the approval of three drugs. Here, we discuss in detail
      the development of IN inhibitors between January 2012 and May 2014, with a
      particular focus on molecular simulation. We highlight controversial aspects of
      computational drug design and refer to alternative practices where appropriate.
      The analysis of these computational approaches provides some useful clues to the
      possible future discovery of novel IN inhibitors. 

PMID- 26220091
TI  - Exploration of individuality in drug metabolism by high-throughput metabolomics:
      The fast line for personalized medicine.
AB  - In many cases, individuality in metabolism of a drug is a reliable predictor of
      the drug efficacy/safety. Modern high-throughput metabolomics is an ideal
      instrument to track drug metabolism in an individual after treatment.
      Productivity and low cost of the metabolomics are sufficient to analyse a large
      cohort of patients to explore individual variations in drug metabolism and to
      discover drug metabolic biomarkers indicative of drug efficacy/safety. The only
      potential disadvantage of metabolomics becoming a routine clinical procedure is a
      need to treat the patient once before making a prognosis. However, in many
      clinical applications this would not be a limitation. Here, we explore current
      opportunities and challenges for translating high-throughput metabolomics into
      the platform for personalized medicine. 

PMID- 26220092
TI  - The Pkn22 Ser/Thr kinase in Nostoc PCC 7120: role of FurA and NtcA regulators and
      transcript profiling under nitrogen starvation and oxidative stress.
AB  - BACKGROUND: The filamentous cyanobacterium Nostoc sp. strain PCC 7120 can fix N2
      when combined nitrogen is not available. Furthermore, it has to cope with
      reactive oxygen species generated as byproducts of photosynthesis and
      respiration. We have previously demonstrated the synthesis of Ser/Thr kinase
      Pkn22 as an important survival response of Nostoc to oxidative damage. In this
      study we wished to investigate the possible involvement of this kinase in
      signalling peroxide stress and nitrogen deprivation. RESULTS: Quantitative RT-PCR
      experiments revealed that the pkn22 gene is induced in response to peroxide
      stress and to combined nitrogen starvation. Electrophoretic motility assays
      indicated that the pkn22 promoter is recognized by the global transcriptional
      regulators FurA and NtcA. Transcriptomic analysis comparing a pkn22-insertion
      mutant and the wild type strain indicated that this kinase regulates genes
      involved in important cellular functions such as photosynthesis, carbon
      metabolism and iron acquisition. Since metabolic changes may lead to oxidative
      stress, we investigated whether this is the case with nitrogen starvation. Our
      results rather invalidate this hypothesis thereby suggesting that the function of
      Pkn22 under nitrogen starvation is independent of its role in response to
      peroxide stress. CONCLUSIONS: Our analyses have permitted a more complete
      functional description of Ser/Thr kinase in Nostoc. We have decrypted the
      transcriptional regulation of the pkn22 gene, and analysed the whole set of genes
      under the control of this kinase in response to the two environmental changes
      often encountered by cyanobacteria in their natural habitat: oxidative stress and
      nitrogen deprivation.

PMID- 26220093
TI  - Small-incision phacotrabeculectomy versus phacoemulsification in refractory acute
      primary angle closure with cataract.
AB  - BACKGROUND: Acute primary angle closure (PAC) can be refractory to conventional
      treatment and intraocular pressure (IOP) is beyond control. Surgical intervention
      should be considered at the moment. The aim of the study was to compare small
      incision phacotrabeculectomy (phacotrab, small-incision trabeculectomy combined
      with phacoemulsification) with phacoemulsification (phaco) in patients with
      refractory acute PAC and coexisting cataract. METHODS: Analyzed 49 eyes (49
      patients) with acute PAC and cataract received small-incision phacotrab (24 eyes)
      or phaco (25 eyes) randomly. All these cases were refractory to conventional
      treatment involved the use of preoperative topical IOP-lowering agents,
      corticosteroids, mannitol, methazolamide and paracentesis to reduce IOP. The
      effects on best corrected visual acuity (BCVA), IOP, anterior chamber depth
      (ACD), glaucoma medications, and complications were observed for twelve months.
      RESULTS: After operation BCVA of 18 patients (75 %) in phacotrab group and 20
      patients (80 %) in phaco group improved compared to preoperative vision. No
      statistically significant differences in mean BCVA were found between the two
      groups. The mean postoperative IOP levels at all follow up time points were lower
      than the mean preoperative IOP in each group (P < 0.001). There was statistically
      significant difference in mean IOP between the two groups only at 12 months
      postoperatively (P = 0.006). The surgical success rate (without medications, IOP
      <= 21 mmHg) was 83.33 % (20 eyes) and 72 % (18 eyes) in phacotrab group and phaco
      group respectively at 12 months. No statistically significant differences in the
      mean ACD were found between the two groups. There were no serious intra- or post
      operative complications in the two treatment groups. CONCLUSIONS: Besides phaco,
      small incision phacotrab may be another effective and safe choice in the
      treatment of patients with refractory acute PAC and coexisting cataract. Whether
      phacotrab is more effective in IOP control in the long term needs to be verified
      in the further.

PMID- 26220094
TI  - Thymidylate synthase gene amplification predicts pemetrexed resistance in
      patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: Thymidylate synthase (TYMS) expression in lung cancer tissue affects
      the therapeutic efficacy of pemetrexed (PMT). TYMS protein expression is
      primarily assessed using immunohistochemistry (IHC), but this method is not
      suitable for accurate quantitative analysis. It is not known whether the analysis
      of TYMS gene copy number using fluorescence in situ hybridization (FISH) is a
      useful method for assessment of TYMS expression. PATIENTS AND METHODS: The
      participants were patients with chemo-naive advanced NSCLC treated with PMT plus
      carboplatin (CBDCA) in prospective clinical phase II study. TYMS expression was
      evaluated in 40 patients by gene copy number and protein expression using FISH
      and IHC. Therapeutic efficacy was evaluated by investigating the response rate
      (RR), disease control rate (DCR), progression-free survival (PFS), and overall
      survival (OS). RESULTS: TYMS gene amplification was detected in 8 patients (32 %)
      among 25 patients who could be evaluated for TYMS gene copy number. There were no
      patients with complete or partial response in the TYMS amplified group. RR and
      DCR were lower in the TYMS amplified group compared with the TYMS unamplified
      group (0 versus 35.3 %, p = 0.0539, 62.5 versus 94.1 %, p = 0.0443). PFS and OS
      were reduced in the TYMS amplified group. The analysis of TYMS gene copy number
      had higher sensitivity and specificity compared with TYMS protein expression
      (76.2 versus 50.0 %, 75.0 versus 66.7 %). CONCLUSION: The analysis of TYMS gene
      copy number is more suitable than TYMS protein expression for assessment of TYMS
      expression. TYMS gene amplification predicts outcome of patients receiving PMT
      with advanced NSCLC.

PMID- 26220095
TI  - The role of human epididymis protein 4 in the diagnosis of epithelial ovarian
      cancer.
AB  - PURPOSE: Epithelial ovarian cancer is one of the most lethal female genital tract
      cancers. Early diagnosis of EOC would benefit the patients a lot. Human
      epididymis protein 4 (HE4) has been regarded as a new powerful biomarker in
      diagnosis of EOC; we hope to obtain system knowledge of HE4 and understand the
      role of HE4 in diagnosis of epithelial ovarian cancer (EOC). METHODS: We searched
      Pubmed, Embase, Medline, and Chinese National Knowledge Infrastructure (CNKI) for
      articles that included HE4's origin, characteristics, detection methods, clinical
      efficacy alone or combined with CA125, the risk of malignancy index, and the risk
      of ovarian malignancy algorithm. The diagnostic performance for the EOC and the
      role in the recurrence and procession in EOC were also discussed. RESULTS: We got
      83 most related articles and found that there were significantly difference
      existing among the studies, such as the clinical characteristics of patients, the
      methodology for measuring HE4, the different cut-offs for HE4 and so on.
      CONCLUSION: HE4 is a promising biomarker for the early diagnosis of EOC. However,
      each lab should establish its own reference internal of HE4.

PMID- 26220096
TI  - Shorter hemodialysis duration is a risk factor for the recurrence of urothelial
      carcinoma of the bladder in patients on maintenance hemodialysis.
AB  - PURPOSE: To investigate the association of hemodialysis duration with the
      recurrence of urothelial carcinoma (UC) of the bladder and overall survival in
      patients undergoing maintenance hemodialysis (MHD). PATIENTS AND METHODS: 52
      bladder cancer patients who underwent MHD at the Xiangya Hospital of The Central
      South University between 2001 and 2011 were enrolled in the study. The patients
      were divided into three groups according to hemodialysis duration, and patient
      mortality and tumor recurrence rates were analyzed. The association of
      hemodialysis duration with occurrence and recurrence of UC of the bladder was
      analyzed by Cox regression analysis. Survival was evaluated by the Kaplan-Meier
      method. RESULTS: Out of 6266 chronic hemodialysis patients, 52 patients had UC of
      the bladder after the initiation of hemodialysis for 6 months. The mean age at
      hemodialysis onset was 55 years (IQR 36, 71). The major complaints were painless
      gross hematuria and urethral bloody discharge. Tumors were generally large and
      multifocal. The standardized incidence ratio of UC of the bladder was 43.9
      compared with general population, and it was higher in women (76.7) and in the
      age group 61-65 years (186.6). The mean hemodialysis duration before the
      diagnosis of bladder cancer was 32 months. 30 (57.7 %) patients received
      hemodialysis no more than 3 years, 10 (19.2 %) patients received hemodialysis
      between 3 and 6 years, and 12 (23.1 %) patients received hemodialysis for more
      than 6 years. CONCLUSION: Preoperative shorter hemodialysis duration is a risk
      factor for the occurrence and recurrence of UC of the bladder in patients
      undergoing MHD.

PMID- 26220097
TI  - Indicators and measurement tools for health system integration: a knowledge
      synthesis protocol.
AB  - BACKGROUND: Health system integration is a key component of health system reform
      with the goal of improving outcomes for patients, providers, and the health
      system. Although health systems continue to strive for better integration,
      current delivery of health services continues to be fragmented. A key gap in the
      literature is the lack of information on what successful integration looks like
      and how to measure achievement towards an integrated system. This multi-site
      study protocol builds on a prior knowledge synthesis completed by two of the
      primary investigators which identified 10 key principles that collectively
      support health system integration. The aim is to answer two research questions:
      What are appropriate indicators for each of the 10 key integration principles
      developed in our previous knowledge synthesis and what measurement tools are used
      to measure these indicators? To enhance generalizability of the findings, a
      partnership between Canada and Brazil was created as health system integration is
      a priority in both countries and they share similar contexts. METHODS/DESIGN:
      This knowledge synthesis will follow an iterative scoping review process with
      emerging information from knowledge-user engagement leading to the refinement of
      research questions and study selection. This paper describes the methods for each
      phase of the study. Research questions were developed with stakeholder input.
      Indicator identification and prioritization will utilize a modified Delphi method
      and patient/user focus groups. Based on priority indicators, a search of the
      literature will be completed and studies screened for inclusion. Quality
      appraisal of relevant studies will be completed prior to data extraction. Results
      will be used to develop recommendations and key messages to be presented through
      integrated and end-of-grant knowledge translation strategies with researchers and
      knowledge-users from the three jurisdictions. DISCUSSION: This project will
      directly benefit policy and decision-makers by providing an easy accessible set
      of indicators and tools to measure health system integration across different
      contexts and cultures. Being able to evaluate the success of integration
      strategies and initiatives will lead to better health system design and improved
      health outcomes for patients.

PMID- 26220098
TI  - Functional characterization of importin alpha8 as a classical nuclear
      localization signal receptor.
AB  - Importin alpha8 has recently been identified as an importin alpha family member
      based on its primary structure and binding ability to importin beta1 and to
      several karyophilic proteins. However, there has been no experimental evidence
      that importin alpha8 actually functions in the nuclear transport of classical
      nuclear localization signal (cNLS)-containing cargo. Here, using an in vitro
      transport assay, we demonstrate that purified recombinant importin alpha8 can
      transport SV40T antigen cNLS-containing cargo into the nucleus of HeLa cells, in
      conjunction with importin beta1. Pull-down assays, followed by mass spectrometry
      analysis, identified 179 putative importin alpha8-binding proteins, only 62 of
      which overlap with those of importin alpha1, the closest importin alpha family
      member. Among the importin alpha8-binding candidates, we showed that DNA damage
      binding protein 2 (DDB2) was actually transported into the nucleus via the
      importin alpha8/beta1 pathway. Furthermore, we found that the other subtypes of
      importin alpha, which were also identified as importin alpha8-binding candidates,
      indeed form heterodimers with importin alpha8. Notably, we found that these
      importin alpha8-containing heterodimers were more stable in the presence of cNLS
      substrates than heterodimers containing importin alpha1. From these findings, we
      propose that importin alpha8 functions as a cNLS receptor with distinct cargo
      specificity, and that heterodimerization by importin alpha8 is a novel regulatory
      mode of cNLS binding, in addition to the autoinhibitory regulation by the
      importin beta binding domain. 

PMID- 26220099
TI  - Protection against dengue disease by synthetic nucleic acid antibody
      prophylaxis/immunotherapy.
AB  - Dengue virus (DENV) is the most important mosquito-borne viral infection in
      humans. In recent years, the number of cases and outbreaks has dramatically
      increased worldwide. While vaccines are being developed, none are currently
      available that provide balanced protection against all DENV serotypes. Advances
      in human antibody isolation have uncovered DENV neutralizing antibodies (nAbs)
      that are capable of preventing infection from multiple serotypes. Yet delivering
      monoclonal antibodies using conventional methods is impractical due to high
      costs. Engineering novel methods of delivering monoclonal antibodies could tip
      the scale in the fight against DENV. Here we demonstrate that simple
      intramuscular delivery by electroporation of synthetic DNA plasmids engineered to
      express modified human nAbs against multiple DENV serotypes confers protection
      against DENV disease and prevents antibody-dependent enhancement (ADE) of disease
      in mice. This synthetic nucleic acid antibody prophylaxis/immunotherapy approach
      may have important applications in the fight against infectious disease. 

PMID- 26220100
TI  - Associations of cardiorespiratory fitness, physical activity, and adiposity with
      arterial stiffness in children.
AB  - Associations of cardiorespiratory fitness (CRF), physical activity (PA),
      sedentary behavior, and body fat percentage (BF%) with arterial stiffness and
      dilation capacity were investigated in 160 prepubertal children (83 girls) 6-8
      years of age. We assessed CRF (watts/lean mass) by maximal cycle ergometer
      exercise test, total PA, structured exercise, unstructured PA, commuting to and
      from school, recess PA and total and screen-based sedentary behavior by
      questionnaire, BF% using dual-energy X-ray absorptiometry, and arterial stiffness
      and dilation capacity using pulse contour analysis. Data were adjusted for sex
      and age. Poorer CRF (standardized regression coefficient beta = -0.297, P <
      0.001), lower unstructured PA (beta = -0.162, P = 0.042), and higher BF% (beta =
      0.176, P = 0.044) were related to higher arterial stiffness. When CRF,
      unstructured PA, and BF% were in the same model, only CRF was associated with
      arterial stiffness (beta = -0.246, P = 0.006). Poorer CRF was also related to
      lower arterial dilation capacity (beta = 0.316, P < 0.001). Children with low CRF
      (< median) and high BF% (>= median; P = 0.002), low CRF and low unstructured PA
      (< median; P = 0.006) or children with low unstructured PA and high BF% (P =
      0.005) had higher arterial stiffness than children in the opposite halves of
      these variables. Poor CRF was independently associated with increased arterial
      stiffness and impaired arterial dilation capacity among children. 

PMID- 26220101
TI  - The accuracy and consistency of rural, remote and outpost triage nurse decision
      making in one Western Australia Country Health Service Region.
AB  - BACKGROUND: The Australasian Triage Scale aims to ensure that the triage category
      allocated, reflects the urgency with which the patient needs medical assistance.
      This is dependent on triage nurse accuracy in decision making. The Australasian
      Triage Scale also aims to facilitate triage decision consistency between
      individuals and organisations. Various studies have explored the accuracy and
      consistency of triage decisions throughout Australia, yet no studies have
      specifically focussed on triage decision making in rural health services.
      Further, no standard has been identified by which accuracy or consistency should
      be measured. Australian emergency departments are measured against a set of
      standard performance indicators, including time from triage to patient review,
      and patient length of stay. There are currently no performance indicators for
      triage consistency. METHODS: An online questionnaire was developed to collect
      demographic data and measure triage accuracy and consistency. The questionnaire
      utilised previously validated triage scenarios.(1) Triage decision accuracy was
      measured, and consistency was compared by health site type using Fleiss' kappa.
      RESULTS: Forty-six triage nurses participated in this study. The accuracy of
      participants' triage decision-making decreased with each less urgent triage
      category. Post-graduate qualifications had no bearing on triage accuracy. There
      was no significant difference in the consistency of decision-making between
      paediatric and adult scenarios. Overall inter-rater agreement using Fleiss' kappa
      coefficient, was 0.4. This represents a fair-to-good level of inter-rater
      agreement. CONCLUSIONS: A standard definition of accuracy and consistency in
      triage nurse decision making is required. Inaccurate triage decisions can result
      in increased morbidity and mortality. It is recommended that emergency department
      performance indicator thresholds be utilised as a benchmark for national triage
      consistency.

PMID- 26220102
TI  - Accelerometer-Based Navigation Is as Accurate as Optical Computer Navigation in
      Restoring the Joint Line and Mechanical Axis After Total Knee Arthroplasty: A
      Prospective Matched Study.
AB  - The Zimmer iASSIST system is a novel accelerometer-based navigation system for
      TKA. 76 patients (76 knees) were prospectively matched for age, BMI, gender,
      diagnosis, and pre-operative scores, and underwent TKA using the iASSIST (n=38)
      or optical CAS (n=38). There were no significant differences in clinical outcomes
      or satisfaction rates at six months post-operatively (P>0.05). Mechanical axis
      was 1.8+/-1.3 degrees  in the iASSIST cohort versus 2.1+/-1.6 degrees  in the CAS
      cohort (P=0.543). There were no significant differences in number of outliers for
      mechanical axis (P=1.000), coronal femoral-component angle (P=0.693), coronal
      tibial-component angle (P=0.204) or joint line deviation (P=1.000). The duration
      of surgery was significantly longer in the CAS group (P<0.001), while the added
      cost of accelerometer-based navigation was approximately $1000 per operation. 

PMID- 26220103
TI  - Increased Aseptic Tibial Failures in Patients With a BMI >=35 and Well-Aligned
      Total Knee Arthroplasties.
AB  - The purpose of this study was to calculate the risk of revision secondary to
      aseptic tibial loosening correlated with increased BMI in 5088 primary TKAs. The
      mean age was 69 years, with a mean follow-up of 7 years. Fifty-two (1.0%)
      revision TKAs were performed due to aseptic tibial loosening, with the 15-year
      risk being 2.7%. Patients with a BMI >=35 kg/m(2) were significantly more likely
      to undergo revision due to aseptic tibial failure (HR=1.9; P<0.05). Coronal
      alignment was equivalent between those who did and did not experience tibial
      loosening. Given that the risk of revision TKA due to aseptic tibial component
      failure is 2-fold greater in those with a BMI of >=35 kg/m(2), consideration
      should be given to additional fixation. Therapeutic Level III. See Instructions
      to Authors for a complete description of levels of evidence.

PMID- 26220104
TI  - Opioid-Based Analgesia: Impact on Total Joint Arthroplasty.
AB  - The objective of this study was to characterize the impact of opioid-based
      analgesia in total joint arthroplasty. The primary outcomes were incidence of in
      hospital complications, length of stay, and discharge destination. Six hundred
      and seventy-three primary total hip and knee arthroplasties were retrospectively
      reviewed. The incidence of opioid-related adverse drug events was 8.5%, which
      accounted for 58.2% of all postoperative complications. Age, anesthesia
      technique, ASA score, and surgery type were significant risk factors for
      complications. After adjusting for these confounders, opioid-related adverse drug
      events were significantly associated with increased length of stay (P < 0.001)
      and discharge to extended care facilities (P = 0.014). 

PMID- 26220105
TI  - Survivorship and Complications of Revision Total Hip Arthroplasty with a Mid
      Modular Femoral Stem.
AB  - We retrospectively reviewed 161 revision THAs with diaphyseal fitting, mid
      modular femoral components performed by ten surgeons at two academic medical
      centers. The average follow-up was 6.1 years. At final follow-up, 4 patients
      required re-revision for failure of the femoral component; 3 (2%) for aseptic
      loosening and 1 for mechanical failure of stem in setting of periprosthetic
      fracture. There were a total of 24 (14.9%) revisions for any reason, with the
      most common reason being septic failure (10 of 24). To our knowledge, this is the
      largest reported series of mid-term survivorship and complications of revision
      THA with mid-modular femoral components. Our results show that these stems have a
      low rate of aseptic loosening, subsidence, and mechanical failure.

PMID- 26220106
TI  - Green sonochemical synthesis of silver nanoparticles at varying concentrations of
      kappa-carrageenan.
AB  - A green sonochemical method was developed for preparing silver nanoparticles (Ag
      NPs) in different concentrations of kappa carrageenan (kappa-carrageenan). The
      kappa-carrageenan was used as a natural eco-friendly stabilizer, and ultrasonic
      irradiation was used as a green reducing agent. The number of Ag-NPs increased
      with increasing kappa-carrageenan concentrations. Formation of Ag/kappa
      carrageenan was determined by UV-visible spectroscopy where the surface plasmon
      absorption maximum was observed at 402 to 420 nm. The X-ray diffraction (XRD)
      analysis showed that the Ag-NPs are of a face-centered cubic structure. The
      Fourier transform infrared (FT-IR) spectrum indicated the presence of Ag-NPs in
      kappa-carrageenan. Transmission electron microscopy (TEM) image for the highest
      concentration of kappa-carrageenan showed the distribution of Ag-NPs with an
      average particle size near to 4.21 nm. Scan electron microscopy (SEM) images
      illustrated the spherical shape of the Ag-NPs. The use of photo irradiation
      provides a green and economic feature to this work. 

PMID- 26220107
TI  - Effect of Anatase Synthesis on the Performance of Dye-Sensitized Solar Cells.
AB  - Anatase nanoparticles were synthesized from a titanium isopropoxide solution
      using a hydrothermal process at different pressures in an autoclave system while
      keeping the volume of the solution constant. As the autoclave pressure was
      increased from 1 to 71 atm (23 to 210  degrees C), the crystal size in the
      nanoparticles increased from 9 to 13.8 nm. The anatase nanoparticles were used to
      build dye-sensitized solar cells (DSSC). Mesoporous films of this oxide were
      deposited over conducting SnO2:F substrates using the screen-printing technique
      and then annealed at 530  degrees C at 1 atm of air pressure. The morphology of
      the mesoporous film surface of anatase, studied using scanning electron
      microscopy, revealed that the crystal size and pore distribution were functions
      of the pressure conditions. The energy band gap of the films as a function of the
      crystal size exhibited quantum effects below 11.8 nm. The effects of the anatase
      synthesis conditions and properties of the mesoporous film on the DSSC-type solar
      cell parameters, eta%, V OC, J SC, and FF, were also investigated: the mesoporous
      anatase films prepared at 200  degrees C (54 atm of pressure in the autoclave)
      and annealed at 530  degrees C in air generated the best solar cell, having the
      highest conversion efficiency. 

PMID- 26220108
TI  - Continuous inhaled iloprost in a neonate with d-transposition of the great
      arteries and severe pulmonary arterial hypertension.
AB  - This report describes the case of a neonate with d-transposition of the great
      arteries and severe pulmonary arterial hypertension stabilised in the post
      operative period with continuous iloprost nebulisation. To our knowledge, this is
      the first documented method of treating post-operative severe pulmonary arterial
      hypertension with continuous inhaled iloprost in a patient with complex CHD. We
      found this method of delivering the drug very effective in stabilising
      haemodynamic swings in the setting of severe pulmonary arterial hypertension. 

PMID- 26220109
TI  - Transanal total mesorectal excision assisted by single-port laparoscopic surgery
      for low rectal cancer.
AB  - INTRODUCTION: We have combined the minimally invasive single-port laparoscopic
      surgery and the transanal total mesorectal excision (TaTME) for rectal cancer
      with the goal to standardize the approach and improve the quality of rectal
      cancer resection. METHODS: By using two single-port platforms, selected patients
      were first operated by TaTME, and then a single-port laparoscopic surgery was
      introduced to assist and complete the abdominal portion. Short-term outcomes
      including perioperative outcome and pathologic results of these patients were
      evaluated. RESULTS: Between July 2014 and March 2015, six patients with low
      rectal cancer (five males and one female) at a median age of 68 years were
      successfully operated in a median time of 360 min (range 310-420). The median
      estimated blood loss was 150 ml (range 50-800). In one patient, the spleen was
      removed because of a lesion identified preoperatively. Their postoperative
      recovery was uneventful except one acute myocardial infarction on postoperative
      day 3. Pathologic specimens showed negative margins and a complete excision of
      the mesorectum in all cases. The median number of harvested lymph nodes was 11.5
      (range 4-12). At a median follow-up of 4 months (range 3-9), after ileostomy
      closure, none of the patients suffered from fecal incontinence. CONCLUSION: TaTME
      assisted by abdominal single-port may be safely achieved in selected rectal
      cancer patients.

PMID- 26220110
TI  - The impact of postpartum contraception on reducing preterm birth: findings from
      California.
AB  - OBJECTIVE: Family planning is recommended as a strategy to prevent adverse birth
      outcomes. The potential contribution of postpartum contraceptive coverage to
      reducing rates of preterm birth is unknown. In this study, we examine the impact
      of contraceptive coverage and use within 18 months of a birth on preventing
      preterm birth in a Californian cohort. STUDY DESIGN: We identified records for
      second or higher-order births among women from California's 2011 Birth
      Statistical Master File and their prior births from earlier Birth Statistical
      Master Files. To identify women who received contraceptive services from publicly
      funded programs, we applied a probabilistic linking methodology to match birth
      files with enrollment records for women with Medi-Cal or Family Planning, Access,
      Care, and Treatment Program (PACT) claims. The length of contraceptive coverage
      was determined through applying an algorithm based on the specified method and
      the quantity dispensed. Preterm birth was defined as a birth occurring <37 weeks'
      gestation, and calculated from the medical record. We further examined
      differences in preterm birth using subcategories defined by the World Health
      Organization: extremely preterm (<28 weeks); very preterm (28 to <32 weeks); and
      moderate to late preterm (32 to <37 weeks). We built a multivariable regression
      model to examine the effect of contraceptive coverage on the odds of a preterm
      birth and control for key covariates. RESULTS: The cohort consisted of 111,948
      women who were seen at least once by a Medi-Cal or Family PACT provider within 18
      months of delivery. Of the cohort, 9.75% had a preterm birth. Contraceptive
      coverage was found to be protective against preterm birth. For every month of
      contraceptive coverage, odds of a preterm birth <37 weeks decrease by 1.1% (odds
      ratio, 0.989; 95% confidence interval, 0.986-0.993). CONCLUSION: Improving
      postpartum contraceptive use has the potential to reduce preterm births.

PMID- 26220112
TI  - Maternal and fetal outcomes of pancreatitis in pregnancy.
AB  - OBJECTIVE: This study examined maternal and neonatal outcomes that are associated
      with pancreatitis in pregnancy, in particular preeclampsia. STUDY DESIGN: We
      conducted a retrospective cohort study of all singleton nonanomalous pregnancies
      in California from 2005-2008 with an identification of all cases of pancreatitis.
      Outcomes of interest included preeclampsia, intrauterine fetal death, preterm
      delivery, and neonatal or infant death. Univariate and multivariable analyses
      were then conducted to examine the association of pancreatitis in pregnancy and
      maternal characteristics and fetal outcomes. RESULTS: Our cohort of 2,039,870
      pregnant women included 342 women (0.017%) with pancreatitis. Pancreatitis in
      pregnancy was not associated significantly with neonatal or infant death. When
      assessing fetal outcomes, pancreatitis was associated with preterm delivery,
      small for gestational age, jaundice, respiratory distress syndrome, and
      intrauterine fetal death (P < .001). Of note, pregnancy-associated pancreatitis
      was found to be associated with preeclampsia and severe preeclampsia in both
      univariate (P < .001) and multivariate analysis after we controlled for potential
      confounders (odds ratio, 4.21 [95% confidence interval, 2.99-5.93]; odds ratio,
      7.85 [95% confidence interval, 5.03-12.24], respectively). CONCLUSION: We found
      that pancreatitis in pregnancy was associated with several adverse maternal
      outcomes; in particular, a strong association existed with preeclampsia, which
      has its own implications and complications surrounding pregnancy management.
      Pancreatitis in pregnancy was also associated with increased risk for preterm
      delivery but not neonatal or infant death, which is consistent with the
      literature.

PMID- 26220111
TI  - Evaluating gestational weight gain recommendations in pregestational diabetes.
AB  - OBJECTIVE: The Institute of Medicine (IOM) does not provide recommendations for
      gestational weight gain (GWG) specific to women with pregestational diabetes. We
      aimed to assess the impact of GWG outside the IOM recommendations on perinatal
      outcomes. STUDY DESIGN: We performed a retrospective cohort study of all
      singletons with pregestational diabetes from 2008 through 2013. Women were
      classified as GWG within, less than, or greater than IOM recommendations for body
      mass index per week of pregnancy. Maternal outcomes examined were cesarean
      delivery, preeclampsia, and percentage of visits with glycemic control (>50%
      blood sugars at goal). Neonatal outcomes were birthweight, small for gestational
      age (<10th percentile), large for gestational age (LGA) (>90th percentile),
      macrosomia (>4000 g), preterm delivery (<37 weeks), and birth injury (shoulder
      dystocia, fracture, brachial plexus injury, cephalohematoma). Groups were
      compared using analysis of variance and chi(2) test, as appropriate. Backwards
      stepwise logistic regression was used to adjust for confounding factors. RESULTS:
      Of 340 subjects, 37 (10.9%) were within, 64 (18.8%) less than, and 239 (70.3%)
      greater than IOM recommendations. The incidence of cesarean delivery,
      preeclampsia, glycemic control, preterm delivery, and birth injury were not
      significantly different between GWG groups. The incidence of LGA and macrosomia
      increased as GWG category increased (adjusted odds ratio [AOR], 3.08; 95%
      confidence interval [CI], 1.13-8.39 and AOR, 4.02; 95% CI, 1.16-13.9,
      respectively) without decreasing the incidence of small for gestational age (AOR,
      0.34; 95% CI, 0.10-1.19). Increases in the risk in LGA and macrosomia were not
      explained by differences in glycemic control by GWG groups. CONCLUSION: Women
      with pregestational diabetes mellitus should be counseled to gain within the IOM
      recommendations to avoid LGA and macrosomic newborns.

PMID- 26220114
TI  - Bodies don't sleep, neither do babies: experiences at the only maternity hospital
      isolation unit in Sierra Leone during the 2014 Ebola epidemic.

PMID- 26220113
TI  - Impact of fetal chromosomal disorders on maternal blood metabolome: toward new
      biomarkers?
AB  - OBJECTIVE: This study aimed at determining the relationship between fetal
      chromosomal disorders (CDs), including trisomy 21 (T21), and on first- and second
      trimester maternal blood plasma, to identify the time-course metabolic
      adaptations to the conditions and the possible new plasma biomarkers.
      Furthermore, a definition of a joint circulatory (plasma) and excretory (urine)
      metabolic description of second-trimester CDs was sought. STUDY DESIGN: Plasma
      was obtained for 119 pregnant women: 74 controls and 45 CD cases, including 22
      T21 cases. Plasma and lipid extracts (for T21 only) were analyzed by nuclear
      magnetic resonance spectroscopy, and data were handled by variable selection and
      multivariate analysis. Correlation analysis was used on a concatenated
      plasma/urine matrix descriptive of second-trimester CD, based on previously
      obtained urine data. RESULTS: CD cases were accompanied by enhanced lipid beta
      oxidation (increased ketone bodies) and underutilization of glucose, pyruvate,
      and citrate. Lower circulating high-density lipoprotein levels were noted, along
      with changes in the proline and methanol in the first trimester, and also the
      urea, creatinine, acetate, and low-density lipoprotein plus very low-density
      lipoprotein in the second trimester and the different urea and creatinine levels,
      suggesting fetal renal dysfunction. In terms of plasma composition, T21 cases
      were indistinguishable from other CDs in the first trimester, whereas in the
      second trimester, increased methanol and albumin may be T21 specific.
      Furthermore, first-trimester lipid extracts of T21 showed decreased levels of
      18:2 fatty acids, whereas in the second trimester, lower levels of 20:4 and 22:6
      fatty acids were noted, possibly indicative of inflammation mechanisms. In both
      trimesters, high classification rates for CDs (88-89%) and T21 (85-92%) generally
      relied on variable selection of nuclear magnetic resonance data. Plasma/urine
      correlations confirmed most metabolic deviations and unveiled possible new ones
      regarding low-density lipoprotein plus very low-density lipoprotein, sugar, and
      gut-microflora metabolisms. CONCLUSION: This work partially confirmed previously
      reported data on first-trimester T21 and provided additional information on time
      course metabolic changes accompanying CD and T21, in particular regarding plasma
      lipid composition. These results demonstrate the potential of plasma metabolomics
      in monitoring and characterizing CD cases; however, validation in larger cohorts
      is desirable.

PMID- 26220124
TI  - 3D detection of colonic polyps by CT colonography: accuracy, pitfalls, and
      solutions by adjunct 2D workup.
AB  - Computed tomography colonography (CTC) enables evaluation of the colon with
      minimal invasiveness. In spite of advances in multidetector CT (MDCT) technology
      and advanced software features, including electronic bowel cleansing (digital
      removal and tagging of fluid and debris), a number of potential pitfalls in the
      evaluation of the 3D volumetric dataset persist. The purpose of this article is
      to illustrate the strengths and potential pitfalls in the detection of colorectal
      polyps using CTC via a primary three-dimensional (3D) approach for evaluation. 

PMID- 26220126
TI  - [Safety in radiology].

PMID- 26220125
TI  - High-powered microwave ablation of larger hepatocellular carcinoma: evaluation of
      recurrence rate and factors related to recurrence.
AB  - AIM: To evaluate the safety and efficacy of high-powered (80-100 W) percutaneous
      microwave ablation (MWA) at a frequency of 2450+/-10 MHz for treating larger
      hepatocellular carcinoma (HCC) and to predict the risk factors of local
      recurrence after high-powered MWA. MATERIALS AND METHODS: The study was approved
      by the Institutional Review Board, and informed consent was waived because of the
      retrospective study design. Forty-five patients with a total of 60 lesions
      received high-power (80-100 W) MWA at a frequency of 2450+/-10 MHz through a
      percutaneous approach that was guided by ultrasound. Of the 60 lesions with a
      maximum tumour measuring 3-8 cm, 46 lesions were 3-5 cm and 14 were 5-8 cm. The
      complete ablation rates, local recurrence rates, complications, and short-term
      survival were analysed. Ten possible risk factors for local recurrence were
      analysed. RESULTS: The complete ablation rates were 82.61% for the first ablation
      and 100% for the second ablation for 3-5 cm lesions. The complete ablation rates
      were 64.29% (82.61% versus 64.29%, p=0.037) for the first ablation and 85.71%
      (100% versus 85.71%, p=0.055) for the second ablation for 5-8 cm lesions. Local
      recurrence was observed in 11 out of the 45 (24.44%) successfully treated
      patients. The 1-year and 2-year survival rates were 95.56% (43/45) and 86.67%
      (39/45), respectively. No procedure-related mortality was observed and no major
      bleeding, liver rupture, or liver abscesses occurred. Univariate analysis showed
      that a positive correlation existed between the number of lesions (p=0.022),
      proximity to the risk area (p=0.001), pre-ablation alpha-fetoprotein (AFP) levels
      (p=0.025), hepatitis B virus (HBV)-DNA replication (p=0.027) and local
      recurrence. Multivariate analysis identified HBV-DNA (p=0.031) and proximity to
      the risk area (p=0.039) as the independent prognosis factors causing
      postoperative HCC local recurrence. CONCLUSION: High-powered MWA of larger
      hepatocellular carcinomas appears to be a safe and effective treatment. HBV-DNA
      and proximity to the risk area appear to be independent predictors of local
      tumour recurrence.

PMID- 26220127
TI  - [Physical interactions in MRI: Some rules of thumb for their reduction].
AB  - Magnetic resonance imaging (MRI) is one of the most powerful and at the same time
      gentlest clinical imaging techniques at the present time; however, the enormous
      physical complexity as well as simple inattentiveness (projectile effect)
      implicate a significant risk potential and place high demands on the MR operator
      to ensure a safe workflow. A sound knowledge of the potential MR interactions is
      the foundation for a safe and profitable operation for all parties.The first part
      of this article deals with the three most important sources of physical
      interaction, i.e. static magnetic field, gradient and high-frequency (HF) fields.
      The paper discusses the differences between each type of field with respect to
      the impact on human beings, the interactions with magnetic and electrically
      conducting objects/implants and the relevant safety standards. Each section is
      followed by simple rules of thumb to minimize potentially unwanted physical MRI
      interactions.

PMID- 26220128
TI  - [Protection of the unborn child in diagnostic and interventional radiological
      procedures].
AB  - The radiation exposure of an unborn child should be principally avoided, whenever
      it is medically reasonably possible; therefore, the identification of pregnant
      patients is the first and the most important step in radiation protection of the
      unborn child. However, in cases of emergency saving the life of the patient has a
      higher priority than the radiation protection of the unborn child. In this review
      article, we present a longitudinal section through the national and international
      literature and guidelines as a basis for radiological management of a (possibly)
      pregnant patient. We also list some radiological procedures recommended in the
      literature for a series of maternal indications considering the contraindications
      of each method during pregnancy and radiation protection of the unborn child. 

PMID- 26220129
TI  - [New aspects from legislation, guidelines and safety standards for MRI].
AB  - Many aspects of magnetic resonance (MR) operation are not directly regulated by
      law but in standards, guidelines and the operating instructions of the MR
      scanner. The mandatory contents of the operating instructions are regulated in a
      central standard of the International Electrotechnical Commission (IEC) 60601-2
      33. In this standard, the application of static magnetic fields in MRI up to 8
      Tesla (T) in the clinical routine (first level controlled mode) has recently been
      approved. Furthermore, the equally necessary CE certification of ultra-high field
      scanners (7-8 T) in Europe is expected for future devices. The existing
      installations will not be automatically certified but will retain their
      experimental status. The current extension of IEC 60601-2-33 introduces a new add
      on option, the so-called fixed parameter option (FPO). This option might also be
      switched on in addition to the established operating modes and defines a fixed
      device constellation and certain parameters of the energy output of MR scanners
      designed to simplify the testing of patients with implants in the future.The
      employment of pregnant workers in an MRI environment is still not generally
      regulated in Europe. In parts of Germany and Austria pregnant and lactating
      employees were prohibited from working in the MR control zone (0.5 mT) in 2014.
      This is based on the mostly unresolved question of the applicability of limits
      for employees (exposure of extremities to static magnetic fields up to 8 T
      allowed) or the thresholds for the general population (maximum 400 mT). According
      to the European Society of Urogenital Radiology (ESUR), the discarding of breast
      milk after i.v. administration of gadolinium-based contrast agents in the case of
      a breastfeeding woman is only recommended when using contrast agents in the
      nephrogenic systemic fibrosis (NSF) high-risk category.

PMID- 26220130
TI  - Marshaling the Variome.

PMID- 26220131
TI  - Richard Graham Hay Cotton 1940-2015.

PMID- 26220132
TI  - Pediatric cancer genomics, a play rather than a portrait.
AB  - Relapsed neuroblastoma is common, frequently lethal and poorly studied and poses
      a major treatment challenge. Two new studies shed light on the genomic landscape
      of recurrent neuroblastoma and demonstrate profound differences between the
      disease at diagnosis and relapse. 

PMID- 26220133
TI  - Counting copy number and calories.
AB  - Copy number variation (CNV) at several genomic loci has been associated with
      different human traits and diseases, but in many cases the findings could not be
      replicated. A new study provides insights into the degree of variation present at
      the amylase locus and calls into question a previous association between amylase
      copy number and body mass index. 

PMID- 26220134
TI  - Running spell-check to identify regulatory variants.
AB  - A major challenge in human genetics is pinpointing which non-coding genetic
      variants affect gene expression and disease risk. A new study in this issue
      describes a broadly applicable approach for this task that explicitly models cell
      type-specific regulatory motifs and generates variant effect predictions that are
      more accurate and interpretable than those of alternative tools. 

PMID- 26220135
TI  - Corrigendum: Transcriptional regulator PRDM12 is essential for human pain
      perception.

PMID- 26220136
TI  - Erratum: The draft genome of the grass carp (Ctenopharyngodon idellus) provides
      insights into its evolution and vegetarian adaptation.

PMID- 26220137
TI  - Corrigendum: Statistical colocalization of genetic risk variants for related
      autoimmune diseases in the context of common controls.

PMID- 26220138
TI  - Surfactant proteins A and D are related to severity of the disease, pathogenic
      bacteria and comorbidity in patients with chronic rhinosinusitis with and without
      nasal polyps.
AB  - BACKGROUND: Surfactant proteins (SP) A and D play a critical role in the innate
      defence of respiratory mucosa. Although numerous studies have focused on the
      importance of surfactant in the lower airways, relatively little is known about
      its role in the upper respiratory system. METHODS: The prospective study was
      conducted with 61 subjects divided into patients with chronic rhinosinusitis with
      nasal polyps (CRSwNP), with chronic rhinosinusitis without nasal polyps (CRSsNP)
      and healthy controls. SP-A and SP-D were detected in nasal lavage fluid (NALF) by
      ELISA and in nasal mucosa by immunohistochemical staining. Severity of the
      diseases assessed by preoperative CT score, presence of comorbidity (allergy and
      bronchial asthma) and bacterial culture from the middle nasal meatus was
      evaluated. RESULTS: In nasal mucosa, SPs were localised in ciliated cells of the
      surface epithelium and serous acini of the submucosal glands. Stronger expression
      of SPs in submucosal glands was observed in CRSwNP and CRSsNP groups in
      comparison with controls. In patients with CRSsNP and more severe form of the
      disease, higher levels of SP-A and SP-D in NALF and stronger immunoreactivity of
      these proteins in nasal mucosa were detected. Identification of pathogenic
      bacteria was associated with higher levels of SP-A and SP-D in NALF and nasal
      mucosa in patients with CRSsNP and control group. Presence of allergy was
      associated with stronger expression of SP-A in submucosal glands in all CRS
      patients and with decreased levels of both SPs in NALF in CRSsNP patients.
      CONCLUSIONS: Surfactant proteins A and D play an important role in innate host
      defence of upper respiratory tract. Different expression of these proteins in
      patients with chronic rhinosinusitis indicates possible novel target of therapy
      in these patients.

PMID- 26220139
TI  - T Cells and Cerebral Ischemic Stroke.
AB  - Stroke results in cerebral inflammation that causes brain injury and triggers
      immunodepression, resulting in an increased incidence of morbidity and mortality
      secondary to remote infection. It is well known that T cells modulate brain
      inflammation after ischemic stroke, and targeting T cells may be an innovative
      therapeutic strategy for stroke treatment. T cell deficiency is neuro-protective,
      but the observed protective effects differ between ischemic models. Recent
      studies suggest different T cell subsets may have distinct effects on the injured
      brain. In addition to their role in cerebral inflammation, T cells also play a
      role in stroke-induced immunodepression. Therefore, T cell-targeted therapies
      designed to provide protection against brain inflammation might paradoxically
      contribute to remote organ infection and mortality. Further investigations are
      required to determine the role of specific T cell subsets in cerebral
      inflammation and stroke-induced immunodepression, the optimal therapeutic window
      for treatment, and the appropriate dose of anti-T cell therapy. 

PMID- 26220140
TI  - In vitro and in vivo host range of Anopheles gambiae densovirus (AgDNV).
AB  - AgDNV is a powerful gene transduction tool and potential biological control agent
      for Anopheles mosquitoes. Using a GFP reporter virus system, we investigated
      AgDNV host range specificity in four arthropod cell lines (derived from An.
      gambiae, Aedes albopictus and Drosophila melanogaster) and six mosquito species
      from 3 genera (An. gambiae, An. arabiensis, An. stephensi, Ae. albopictus, Ae.
      aegypti and Culex tarsalis). In vitro, efficient viral invasion, replication and
      GFP expression was only observed in MOS55 An. gambiae cells. In vivo, high levels
      of GFP were observed in An. gambiae mosquitoes. Intermediate levels of GFP were
      observed in the closely related species An. arabiensis. Low levels of GFP were
      observed in An. stephensi, Ae. albopictus, Ae. aegypti and Cx. tarsalis. These
      results suggest that AgDNV is a specific gene transduction tool for members of
      the An. gambiae species complex, and could be potentially developed into a
      biocontrol agent with minimal off-target effects. 

PMID- 26220141
TI  - Identification and functional characterization of a novel transglutaminase 1 gene
      mutation associated with autosomal recessive congenital ichthyosis.
AB  - BACKGROUND: Autosomal recessive congenital ichthyosis (ARCI) is a group of
      genetically heterogeneous diseases. Mutations in transglutaminase (TGase) 1 gene
      (TGM1, OMIM 190195) have been implicated in ARCI. However, little is known about
      TGM1 mutations in the Chinese population, and no functional studies have
      investigated the biological effect of mutant TGM1 on human epidermal
      keratinocytes (HaCaT) cells. OBJECTIVES: To identify the pathogenic mutations of
      TGM1 gene in two Chinese siblings with ARCI and gain insight into functional
      consequences of these mutations. METHODS: Fifteen exons and flanking splice sites
      of TGM1 gene were amplified by polymerase chain reaction and then underwent
      bidirectional Sanger sequencing. The HaCaT cells were transfected with lentiviral
      vectors, which overexpressed either wild-type or mutant TGM1 cDNAs with deleted
      homeodomain. Cell proliferation and cell cycle progression were detected. The
      expression of cyclin D1, cyclin B1, CDK4, TGM1, K10, involucrin, and filaggrin
      proteins were investigated by Western blot analysis. RESULTS: We found two
      compound heterozygous missense mutations (c.515C>T, R143C in exon 3 and c.759C>T,
      S212F in exon 4) in both siblings. HaCaT cells transfected with mutant TGM1 cDNAs
      displayed a lower growth rate and delayed S phase while overexpression of wild
      type TGM1 cDNAs led to accelerated growth. HaCaT cells transfected with mutant
      TGM1 cDNAs displayed lower expression of differentiation markers such as
      involucrin and filaggrin. Our findings suggest that the compound heterozygous
      missense (c.515C>T, R143C) mutations in exon 3 and missense (c.759C>T, S212F)
      mutations in exon 4 result in the phenotype of ARCI. TGM1 mutations can suppress
      keratinocyte growth and cornified cell envelope formation.

PMID- 26220142
TI  - A risk management model for familial breast cancer: A new application using Fuzzy
      Cognitive Map method.
AB  - Breast cancer is the most deadly disease affecting women and thus it is natural
      for women aged 40-49 years (who have a family history of breast cancer or other
      related cancers) to assess their personal risk for developing familial breast
      cancer (FBC). Besides, as each individual woman possesses different levels of
      risk of developing breast cancer depending on their family history, genetic
      predispositions and personal medical history, individualized care setting
      mechanism needs to be identified so that appropriate risk assessment, counseling,
      screening, and prevention options can be determined by the health care
      professionals. The presented work aims at developing a soft computing based
      medical decision support system using Fuzzy Cognitive Map (FCM) that assists
      health care professionals in deciding the individualized care setting mechanisms
      based on the FBC risk level of the given women. The FCM based FBC risk management
      system uses NHL to learn causal weights from 40 patient records and achieves a
      95% diagnostic accuracy. The results obtained from the proposed model are in
      concurrence with the comprehensive risk evaluation tool based on Tyrer-Cuzick
      model for 38/40 patient cases (95%). Besides, the proposed model identifies high
      risk women by calculating higher accuracy of prediction than the standard Gail
      and NSAPB models. The testing accuracy of the proposed model using 10-fold cross
      validation technique outperforms other standard machine learning based inference
      engines as well as previous FCM-based risk prediction methods for BC. 

PMID- 26220143
TI  - Glucuronidation of estrone and 16alpha-hydroxyestrone by human UGT enzymes: The
      key roles of UGT1A10 and UGT2B7.
AB  - The glucuronidation of estrone and 16alpha-hydroxyestrone by recombinant human
      UDP-glucuronosyltransferase enzymes (UGTs) of subfamilies 1A, 2A and 2B was
      studied. Microsomes from human liver and small intestine were also tested for the
      glucuronidation of these two estrogens. The results revealed that UGT1A10 is by
      far the most active enzyme in estrone glucuronidation. UGT1A10 also exhibited
      high rate of 16alpha-hydroxyestrone conjugation at the 3-OH, whereas UGT2B7
      catalyzed its glucuronidation at high rates at the 16-OH. Human liver microsomes
      exhibited high rates of 16alpha-hydroxyestrone-16-glucuronide formation, but very
      low formation rates of either 16alpha-hydroxyestrone-3-glucuronide or estrone
      glucuronide. On the other hand, human intestine microsomes catalyzed the
      formation of all these 3 different glucuronides at high rates. Kinetic analyses
      revealed very low Km value for 16alpha-hydroxyestrone glucuronidation by UGT2B7,
      below 4 MUM, suggesting higher affinity than commonly found among UGTs and their
      substrates. In further studies with UGT1A10, mutant F93G exhibited increased
      glucuronidation rates of 16alpha-hydroxyestrone, but not estrone, whereas
      mutations in F90 did not reveal any activity with either estrogen. Taken
      together, the results of this study significantly expand our understanding on the
      metabolism of estrogens and their interactions with the human UGTs.

PMID- 26220144
TI  - Age-related changes in emotional face processing across childhood and into young
      adulthood: Evidence from event-related potentials.
AB  - Socio-emotional processing is an essential part of development, and age-related
      changes in its neural correlates can be observed. The late positive potential
      (LPP) is a measure of motivated attention that can be used to assess emotional
      processing; however, changes in the LPP elicited by emotional faces have not been
      assessed across a wide age range in childhood and young adulthood. We used an
      emotional face matching task to examine behavior and event-related potentials
      (ERPs) in 33 youth aged 7-19 years old. Younger children were slower when
      performing the matching task. The LPP elicited by emotional faces but not control
      stimuli (geometric shapes) decreased with age; by contrast, an earlier ERP (the
      P1) decreased with age for both faces and shapes, suggesting increased efficiency
      of early visual processing. Results indicate age-related attenuation in emotional
      processing that may stem from greater efficiency and regulatory control when
      performing a socio-emotional task.

PMID- 26220145
TI  - Digital tomosynthesis and high resolution computed tomography as clinical tools
      for vertebral endplate topography measurements: Comparison with microcomputed
      tomography.
AB  - Endplate morphology is understood to play an important role in the mechanical
      behavior of vertebral bone as well as degenerative processes in spinal tissues;
      however, the utility of clinical imaging modalities in assessment of the
      vertebral endplate has been limited. The objective of this study was to evaluate
      the ability of two clinical imaging modalities (digital tomosynthesis, DTS; high
      resolution computed tomography, HRCT) to assess endplate topography by
      correlating the measurements to a microcomputed tomography (MUCT) standard. DTS,
      HRCT, and MUCT images of 117 cadaveric thoracolumbar vertebrae (T10-L1; 23 male,
      19 female; ages 36-100 years) were segmented, and inferior and superior endplate
      surface topographical distribution parameters were calculated. Both DTS and HRCT
      showed statistically significant correlations with MUCT approaching a moderate
      level of correlation at the superior endplate for all measured parameters
      (R(2)Adj=0.19-0.57), including averages, variability, and higher order
      statistical moments. Correlation of average depths at the inferior endplate was
      comparable to the superior case for both DTS and HRCT (R(2)Adj=0.14-0.51), while
      correlations became weak or nonsignificant for higher moments of the topography
      distribution. DTS was able to capture variations in the endplate topography to a
      slightly better extent than HRCT, and taken together with the higher speed and
      lower radiation cost of DTS than HRCT, DTS appears preferable for endplate
      measurements.

PMID- 26220146
TI  - Kcnh2 and Kcnj8 interactively regulate skin wound healing and regeneration.
AB  - Previous studies indicate that ion channels are mediators of bioelectricity
      promoting wound closure/regeneration in nonmammalian, lower vertebrate systems.
      The role of ion channels however in regeneration of wounds in mammalian systems
      that do not regenerate as adults is not yet defined. Using a mammalian model
      system that allows us to determine differentially expressed genes when skin
      regenerates and when skin does not regenerate after wound induction, we
      identified two potassium channels, kcnh2 and kcnj8, to be (1) differentially
      expressed between the two states and (2) highly expressed after wound induction
      at the nonregenerative state. We also found that kcnh2 small molecule inhibitor
      enhanced wound healing while kcnj8 small molecule inhibitor did not. In contrast,
      kcnj8 activator accelerated wound healing and even augmented the effect of kcnh2
      inhibition. These results provide evidence for the first time that potassium
      channels may mediate skin wound healing and regeneration interactively. 

PMID- 26220147
TI  - Implementation of Safe Patient Handling in the U.S. Veterans Health System: A
      Qualitative Study of Internal Facilitators' Perceptions.
AB  - BACKGROUND: Although the literature has noted the positive effects of
      facilitation in implementation research, little is known about what facilitators
      do or how they increase adoption of a program. The purpose of this study was to
      understand internal facilitation activities in implementing a national safe
      patient handling program from the perspective of facility coordinators who
      implemented the program. METHODS: Using a qualitative descriptive design, data
      were collected in five focus groups at two international Safe Patient Handling
      and Mobility Conferences. Participants were 38 facility coordinators implementing
      a safe patient handling program in the Department of Veterans Affairs medical
      centers throughout the United States. Data were analyzed using direct content
      analysis to gather descriptions of internal facilitation. RESULTS: The internal
      facilitation process involved engaging multiple disciplines and levels of
      leadership for implementation. Fifty-four facilitation activities were
      identified, including five activities not currently listed in an existing
      taxonomy. Key characteristics and skills of facilitators included persistence,
      credibility and clinical experience, and leadership and project management
      experience. Themes were mapped onto an existing framework and taxonomy of
      facilitation activities. LINKING EVIDENCE TO ACTION: Internal facilitation is
      both an implementation intervention and a process involving a wide range of
      activities. The findings provide an understanding of what internal facilitators
      are doing to support practice changes and the characteristics and skills of
      internal facilitators that are likely to result in long-term organizational
      change. Five recommendations for action address organizations, senior leaders,
      and internal facilitators.

PMID- 26220148
TI  - Effect of centre-edge angle on clinical and quality of life outcomes after
      arthroscopic acetabular labral debridement.
AB  - PURPOSE: The aim of this study was to compare clinical and quality of life
      outcomes following arthroscopic acetabular labral debridement between patients
      with different centre-edge (CE) angle. METHODS: A total of 79 patients who
      underwent hip labral debridement were enrolled in this study. Radiographic
      measurements of CE angle were collected, and patients were assigned into a normal
      group (25 degrees  < CE angle <40 degrees , n = 68) and dysplasia group (CE angle
      <20 degrees , n = 11). Clinical outcomes were evaluated by modified Harris Hip
      Score (mHHS), Hip Outcome Score (HOS) for activities of daily living (ADL) and
      sports and Short Form 12 (SF-12). RESULTS: At the final follow-up, the normal
      group showed significant improvements in mHHS, HOS (ADL and sports) and SF-12 (P
      < 0.05). However, the dysplasia group revealed significant improvements in mHHS,
      HOS (ADL) and SF-12 physical component summary (PCS) (P < 0.05) and no
      significant changes in HOS sports and SF-12 mental component summary (MCS) (P >
      0.05). Additionally, there was a greater improvement in clinical scores post
      operatively in the normal group compared with the dysplasia group (P < 0.05).
      CONCLUSIONS: Arthroscopic acetabular labral debridement resulted in significantly
      greater clinical and quality of life outcomes in patients with CE angle >25
      degrees  compared with patients with CE angle < 20 degrees .

PMID- 26220149
TI  - Algorithm that delivers an individualized rapid-acting insulin dose after morning
      resistance exercise counters post-exercise hyperglycaemia in people with Type 1
      diabetes.
AB  - AIMS: To develop an algorithm that delivers an individualized dose of rapid
      acting insulin after morning resistance exercise to counter post-exercise
      hyperglycaemia in individuals with Type 1 diabetes. METHODS: Eight people with
      Type 1 diabetes, aged 34 +/- 7 years with HbA1c concentrations 72 +/- 12 mmol/mol
      (8.7 +/- 1.1%), attended our laboratory on two separate mornings after fasting,
      having taken their usual basal insulin the previous evening. These people
      performed a resistance exercise session comprising six exercises for two sets of
      10 repetitions at 60% of the maximum amount of force that was generated in one
      maximal contraction (60% 1RM). In a randomized and counterbalanced order, the
      participants were administered an individualized dose of rapid-acting insulin (2
      +/- 1 units, range 0-4 units) immediately after resistance exercise (insulin
      session) by means of an algorithm or were not administered this (no-insulin
      session). Venous blood glucose concentrations were measured for 125 min after
      resistance exercise. Data (mean +/- sem values) were analysed using anova (P <=
      0.05). RESULTS: Participants had immediate post-resistance exercise
      hyperglycaemia (insulin session 13.0 +/- 1.6 vs. no-insulin session 12.7 +/- 1.5
      mmol/l; P = 0.834). The decline in blood glucose concentration between peak and
      125 min after exercise was greater in the insulin exercise session than in the no
      insulin session (3.3 +/- 1.0 vs. 1.3 +/- 0.4 mmol/l: P = 0.015). There were no
      episodes of hypoglycaemia (blood glucose <3.9 mmol/l). CONCLUSIONS:
      Administration of rapid-acting insulin according to an individualized algorithm
      reduced the hyperglycaemia associated with morning resistance exercise without
      causing hypoglycaemia in the 2 h post-exercise period in people with Type 1
      diabetes.

PMID- 26220150
TI  - Extended RAS analysis for anti-epidermal growth factor therapy in patients with
      metastatic colorectal cancer.
AB  - RAS family proteins (including KRAS and NRAS) play important roles in the
      epidermal growth factor receptor (EGFR) signaling pathway. Mutations in RAS genes
      (occurring at loci in exons 2, 3, and 4) often result in constitutive activation
      of RAS proteins and persistent downstream signaling. Mutations in KRAS exon 2
      (codon 12/13) are an established predictor of lack of response to the anti-EGFR
      monoclonal antibodies cetuximab and panitumumab in patients with metastatic
      colorectal cancer (mCRC), and have been used routinely in clinical practice to
      identify patients unlikely to derive benefit from these therapies. However, a
      meaningful proportion of patients with mCRC have tumors bearing other mutations
      in RAS genes. Recent studies have demonstrated that evaluation of an extended
      panel of RAS mutations-including mutations in KRAS exon 2, 3, and 4 and NRAS
      exons 2, 3, and 4-can better define the patient population that is unlikely to
      benefit from anti-EGFR therapy, with concomitant improvements in outcomes in the
      more highly selected RAS wild-type group. This discovery has changed the practice
      of oncology and has the potential to spare patients from exposure to ineffective
      therapy. In the near future, it is important for the oncology community to
      validate extended RAS analysis assays and make certain that patients who are
      candidates for anti-EGFR therapy undergo appropriate testing and treatment.

PMID- 26220151
TI  - Scoping review of research in Australia on the co-occurrence of physical and
      serious mental illness and integrated care.
AB  - The physical health of people with serious mental illness (SMI) has become a
      focal area of research. The aim of the present study was to ascertain the
      attention and distribution of research from within Australia on physical illness
      and SMI co-occurrence, and to identify gaps. A scoping review of peer-reviewed
      research literature from Australia, published between January 2000 and March
      2014, was undertaken through an electronic literature search and coding of papers
      to chart trends. Four trends are highlighted: (i) an almost threefold increase in
      publications per year from 2000-2006 to 2007-2013; (ii) a steady release of
      literature reviews, especially from 2010; (iii) health-related behaviours,
      smoking, integrated-care programmes, and antipsychotic side-effects as the most
      common topics presented; and (iv) paucity of randomized, controlled trials on
      integrated-care models. Despite a marked increase in research attention to poorer
      physical health, there remains a large gap between research and the scale of the
      problem previously identified. More papers were descriptive or reviews, rather
      than evaluations of interventions. To foster more research, 12 research gaps are
      outlined. Addressing these gaps will facilitate the reduction of inequalities in
      physical health for people with SMI. Mental health nurses are well placed to lead
      multidisciplinary, consumer-informed research in this area. 

PMID- 26220152
TI  - Interleukin-6 and risk of colorectal cancer: results from the CLUE II cohort and
      a meta-analysis of prospective studies.
AB  - PURPOSE: The association between prediagnostic interleukin-6 (IL-6)
      concentrations and risk of colorectal cancer was evaluated in a nested case
      control study and a meta-analysis of prospective studies. METHODS: Colorectal
      cancer cases (n = 173) and matched controls (n = 345) were identified between
      1989 and 2000 among participants in the CLUE II cohort of Washington Country,
      Maryland. Matched odds ratios and the corresponding 95 % confidence intervals
      (CIs) were estimated using conditional logistic regression models. RESULTS:
      Participants in the highest third of plasma IL-6 concentration had a 2.48 times
      higher risk of colon cancer compared to participants in the bottom third (95 % CI
      1.26-4.87; p-trend 0.02) after multivariate adjustment. This association did not
      differ according to the stage of disease, age, sex, or other potential modifying
      variables and remained statistically significant after adjustment for C-reactive
      protein concentrations. No statistically significant association was observed for
      rectal cancer risk. The meta-analysis of six prospective studies yielded an
      increased but borderline statistically significant risk of colon cancer per 1 U
      increase in naturally logarithm-transformed IL-6 (summary RR 1.22; 95 % CI 1.00
      1.49; I (2) 46 %). An inverse association was noted for rectal cancer (RR 0.69;
      95 % CI 0.54-0.88; I (2) 0 %), but there was evidence for small-study effects (p
      0.02). CONCLUSION: Our findings provide support for a modest positive association
      between IL-6 concentrations and colon cancer risk. More work is needed to
      determine whether IL-6 is a valid marker of colorectal inflammation and whether
      such inflammation contributes to colon and rectal cancer risk.

PMID- 26220154
TI  - Portable power supply options for positive airway pressure devices.
AB  - INTRODUCTION: Patients with obstructive sleep apnea (OSA) often face the
      challenge of how to power their positive airway pressure (PAP) devices when
      alternating current power supplies are not available in remote areas with lack of
      electricity or frequent power outages. This article elucidates portable power
      supply options for PAP devices with the aim to increase alternative power source
      awareness among medical providers. METHODS: A search of scientific databases
      (Medline, Scopus, Web of Science, Google Scholar, and the Cochrane Library) was
      carried out on the topic of alternative portable power supply options for
      treatment of OSA. RESULTS: Scientific databases listed above yielded only limited
      results. Most articles were found via Google search. These articles were reviewed
      for alternative power supply options for OSA patients when alternating current is
      not available. The power supply options in this article include lead-acid
      batteries (starter, marine and deep-cycle batteries), lithium ion batteries,
      solar kits, battery packs, backup power systems, portable generators, and travel
      size PAP devices. CONCLUSIONS: There are several options to power PAP devices
      with direct current when alternating current is not available. Knowledgeable
      primary care physicians especially in rural and remote areas can help OSA
      patients improve PAP compliance in order to mitigate morbidity and long-term
      complications of OSA.

PMID- 26220153
TI  - Effects of in vitro hemodilution with crystalloids, colloids, and plasma on
      canine whole blood coagulation as determined by kaolin-activated
      thromboelastography.
AB  - OBJECTIVE: To investigate the effects of in vitro hemodilution with lactated
      Ringers solution (LRS), hetastarch (HES), and fresh frozen plasma (FFP) on whole
      blood coagulation in dogs as assessed by kaolin-activated thromboelastography.
      DESIGN: In vitro experimental study. SETTING: University teaching hospital.
      ANIMALS: Six healthy client-owned dogs. INTERVENTIONS: Whole blood was collected
      and diluted in vitro at a 33% and 67% dilution with either LRS, HES, or FFP.
      MEASUREMENTS AND MAIN RESULTS: Kaolin-activated thromboelastography was performed
      on each sample as well as a control. Thromboelastographic parameters R (min),
      alpha (deg), K (min), and MA (mm) were measured and compared to the sample
      control for each dilution using mixed model methodology. Prolongation in
      coagulation times were seen at both dilutions with LRS and HES. There was no
      significant difference in R times at the 33% dilution, but R time was
      significantly prolonged at the 67% dilution with HES (P = 0.004). MA was
      significantly decreased for LRS at both dilutions (P = 0.013, P < 0.001) and more
      profoundly decreased for HES (P < 0.001, P = 0.006). No significant difference in
      any parameter was found for FFP. CONCLUSIONS: In vitro hemodilution of whole
      blood with both LRS and HES but not FFP resulted in significant effects on
      coagulation with HES having a more profound effect. In vivo evaluation of changes
      in coagulation with various resuscitation fluids is warranted and may be
      clinically relevant.

PMID- 26220155
TI  - Cytosolic sensing of aberrant DNA: arming STING on the endoplasmic reticulum.
AB  - INTRODUCTION: Detection of pathogen-derived nucleic acids is a general and
      effective strategy used by the host to perceive the presence of invading
      microorganisms and initiate an innate immune response. However, inappropriate
      detection of aberrant self nucleic acids is implicated in the development of
      autoimmune diseases. Recently, ER-resident stimulator of interferon genes (STING)
      has been uncovered as a key component in the innate immune response to cytosolic
      nucleic acids and a direct sensor for bacterial cyclic dinucleotides. The
      elucidation of STING-mediated signaling will provide insight into host-microbial
      interactions and contribute to the development of novel strategies for anti
      infection therapies. AREAS COVERED: This review summarizes the cellular and
      molecular processes of host sensing and responding to microbial or endogenous
      aberrant DNA species, highlighting the essential function of STING and the
      corresponding regulatory mechanisms. The authors also attempt to delineate the
      role for the DNA-sensing signaling during the onset and progression of autoimmune
      diseases and suggest improvements in the immunogenicity of DNA vaccines. EXPERT
      OPINION: It is essential to elucidate how the STING-dependent signaling mediates
      the DNA vaccines action as well as the pathogenesis of autoimmune diseases. The
      relevant knowledge will greatly benefit the treatment of infectious diseases and
      identify potential targets for effective drug design.

PMID- 26220156
TI  - Dietziamides, novel tetramic acid dimers from Dietzia timorensis MZ-3 with
      antioxidative activity.
AB  - Dietziamides A and B, two novel tetramic acid dimers, were isolated from the rare
      actinomycetes Dietzia timorensis MZ-3 in the course of our HPLC-diode array
      screening of our collection of terrestrial actinomycetes. The spectroscopic
      analysis revealed the chemical structures of the first secondary metabolites
      characterized in the genus Dietzia. Dietziamides A and B showed moderate DPPH
      (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activities. 

PMID- 26220157
TI  - Human SIRT3 tripeptidic inhibitors containing N(epsilon)-thioacetyl-lysine.
AB  - Built upon our lead pan-SIRT1/2/3 tripeptidic inhibitors that contain the
      catalytic mechanism-based sirtuin inhibitory warhead N(epsilon)-thioacetyl
      lysine, three of their analogs (i.e., 7, 9, and 19) were discovered in the
      current study to exhibit a significantly enhanced SIRT3 inhibitory selectivity
      while maintaining the SIRT3 inhibitory potency. These compounds represent novel
      lead compounds for developing more potent and selective SIRT3 inhibitors of the
      catalytic mechanism-based type. 

PMID- 26220158
TI  - Aryl amide small-molecule inhibitors of microRNA miR-21 function.
AB  - MicroRNAs (miRNAs) are single stranded RNA molecules of ~22 nucleotides that
      negatively regulate gene expression. MiRNAs are involved in fundamental cellular
      processes, such as development, differentiation, proliferation, and survival.
      MiRNA misregulation has been linked to various human diseases, most notably
      cancer. MicroRNA-21 (miR-21), a well-established oncomiR, is significantly
      overexpressed in many types of human cancers, thus rendering miR-21 a potential
      therapeutic target. Using a luciferase-based reporter assay under the control of
      miR-21 expression, a high-throughput screen of >300,000 compounds led to the
      discovery of a new aryl amide class of small-molecule miR-21 inhibitors.
      Structure-activity relationship (SAR) studies resulted in the development of four
      aryl amide derivatives as potent and selective miR-21 inhibitors. The
      intracellular levels of various miRNAs in HeLa cells were analyzed by qRT-PCR
      revealing specificity for miR-21 inhibition over other miRNAs. Additionally,
      preliminary mechanism of action studies propose a different mode of action
      compared to previously reported miR-21 inhibitors, thus affording a new chemical
      probe for future studies. 

PMID- 26220159
TI  - Improving organic tandem solar cells based on water-processed nanoparticles by
      quantitative 3D nanoimaging.
AB  - Organic solar cells have great potential for upscaling due to roll-to-roll
      processing and a low energy payback time, making them an attractive sustainable
      energy source for the future. Active layers coated with water-dispersible
      Landfester particles enable greater control of the layer formation and easier
      access to the printing industry, which has reduced the use of organic solvents
      since the 1980s. Through ptychographic X-ray computed tomography (PXCT), we image
      quantitatively a roll-to-roll coated photovoltaic tandem stack consisting of one
      bulk heterojunction active layer and one Landfester particle active layer. We
      extract the layered morphology with structural and density information including
      the porosity present in the various layers and the silver electrode with high
      resolution in 3D. The Landfester particle layer is found to have an undesired
      morphology with negatively correlated top- and bottom interfaces, wide thickness
      distribution and only partial surface coverage causing electric short circuits
      through the layer. By top coating a polymer material onto the Landfester
      nanoparticles we eliminate the structural defects of the layer such as porosity
      and roughness, and achieve the increased performance larger than 1 V expected for
      a tandem cell. This study highlights that quantitative imaging of weakly
      scattering stacked layers of organic materials has become feasible by PXCT, and
      that this information cannot be obtained by other methods. In the present study,
      this technique specifically reveals the need to improve the coatability and layer
      formation of Landfester nanoparticles, thus allowing improved solar cells to be
      produced. 

PMID- 26220160
TI  - ZEB2/SIP1 as novel prognostic indicator in eyelid sebaceous gland carcinoma.
AB  - Epithelial-mesenchymal transition (EMT) plays a pivotal role in tumor invasion
      and metastasis in various malignancies. ZEB2/SIP1 is an important EMT regulator
      and down-regulates E-cadherin expression. The present study was planned to
      explore status of EMT-associated markers ZEB2/SIP1 and E-cadherin in eyelid
      sebaceous gland carcinoma (SGC) and to correlate with clinicopathological high
      risk features. Expressions of ZEB2 and E-cadherin were evaluated by
      immunohistochemistry in 65 cases of histopathologically proven eyelid SGC. The
      results were correlated with clinicopathological high-risk features and survival
      of the patients to determine the prognostic significance of ZEB2, E-cadherin, and
      various high-risk features. Cytoplasmic overexpression of ZEB2 and membranous
      loss of E-cadherin were seen in 68% and 66% of cases of eyelid SGC, respectively.
      ZEB2 overexpression was significantly associated with E-cadherin loss (P = .002).
      Overexpression of ZEB2 also showed significant association with lymph node
      metastasis (P = .046), orbital invasion (P = .049), large tumor size (P = .018),
      and advanced tumor stages (P = .036). Survival analysis revealed that patients
      with ZEB2 overexpression had poor survival. ZEB2 overexpression and orbital
      invasion were found to be independent prognostic indicators (univariate
      analysis). However, multivariate analysis showed that ZEB2 (hazard ratio, 0.094;
      95% confidence interval, 00.012-0.709; P = .022) was the best poor prognostic
      indicator of eyelid SGC. Our study demonstrates the role of both ZEB2 and E
      cadherin in the promotion of EMT in eyelid SGC. The outcome of this study also
      points toward ZEB2 as an independent prognostic marker as well as a potential
      therapeutic target in eyelid SGC. 

PMID- 26220161
TI  - High-risk human papillomavirus infection involving multiple anatomic sites of the
      female lower genital tract: a multiplex real-time polymerase chain reaction-based
      study.
AB  - High-risk human papillomavirus infection usually is seen at one anatomic site in
      an individual. Rarely, infection at multiple anatomic sites of the female lower
      genital tract in the same individual is encountered either simultaneously and/or
      at a later date. The current study identifies the various subtypes of high-risk
      human papillomavirus infection in these scenarios and analyzes the potential
      significance of these findings. High-risk human papillomavirus infection
      involving 22 anatomic sites from 7 individuals was identified after institutional
      review board approval. Residual paraffin-embedded tissue samples were retrieved,
      and all 15 high-risk human papillomavirus were identified and viral load
      quantified using multiplex real-time polymerase chain reaction-based method.
      Multiple high-risk human papillomavirus subtypes were identified in 32% of the
      samples and as many as 5 different subtypes of high-risk human papillomavirus
      infection in a single anatomic site. In general, each anatomic site has unique
      combination of viral subtypes, although one individual showed overlapping
      subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare
      subtypes are more frequent in younger patients and in dysplasia compared with
      carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk
      human papillomavirus infection in 60% of cases. 

PMID- 26220162
TI  - Solitary (juvenile) xanthogranuloma: a comprehensive immunohistochemical study
      emphasizing recently developed markers of histiocytic lineage.
AB  - Solitary (juvenile) xanthogranuloma (SXG) is an uncommon, benign lesion that
      usually occurs in children. The cell of origin of SXG has been the subject of
      debate, with hypotheses including endothelium, dermal dendrocytes, dermal
      indeterminate cells, and the plasmacytoid monocyte, among others. We further
      characterized the immunophenotype of SXG with an extended immunohistochemical
      panel, paying special attention to recently described or novel markers of
      histiocytic lineage. Forty-one SXG and 23 benign fibrous histiocytomas (BFHs)
      were immunostained for factor XIIIa, CD4, CD11c, CD163, CD31, CD45, lysozyme, and
      S-100. The mononuclear cells of SXG and the spindled cells of BFH were scored as
      "negative," "1+" (<10% positive), "2+" (10%-50% positive), and "3+" (>50%
      positive). SXG immunohistochemistry showed the following: factor XIIIa, 35/40
      (88%); CD4, 34/36 (94%); CD11c, 36/37 (97%); CD163, 36/36 (100%); CD31, 14/31
      (45%); CD45, 14/32 (44%); lysozyme, 23/30 (77%); and S-100, 0/32 (0%). The 5
      factor XIIIa-negative cases all showed 2+-3+ CD4, CD11c, and CD163 expression. In
      contrast, only 8 (35%) of 23 BFH cases were factor XIIIa positive. All other
      stains were universally negative in the lesional cells of BFH, although these
      tumors frequently contained interspersed cells expressing various histiocytic
      markers. Our results strongly support histiocytic lineage for the mononuclear
      cells of SXG. CD11c expression has not been previously described in SXG. CD163
      expression appears to be characteristic of SXG, as it was not expressed by the
      lesional cells of BFH, in contrast to previous reports. CD31 expression in SXG
      represents a potential diagnostic pitfall, as many (dermato)pathologists are
      unaware of CD31 expression in histiocytes. 

PMID- 26220163
TI  - Strong Electronic Selectivity in the Shallow Core Excitation of the CH2Cl2
      Molecule.
AB  - The photoexcitation and multiphotoionization of the dichloromethane molecule have
      been studied for photons with energies from 100 eV to the Cl 2p edge, using the
      time-of-flight multicoincidence technique and synchrotron radiation. The
      electronic de-excitation gives rise to one to three electrons and an ionic
      molecule that decays onto smaller moieties through several fragmentation
      channels. To discern the channels, sets of fragments have been dispersed in time,
      measured in coincidence, and recorded as a function of incident photon energy.
      The chlorine ion, Cl(+), has the highest intensity around and above the Cl 2p
      edge, while the CHnCl(+) ion, corresponding to the loss of one neutral chlorine
      atom, dominates the mass spectra in the valence region. In addition, strong
      electronic selectivity has been observed for the core-excited molecule. 

PMID- 26220164
TI  - How smart can it be: transcriptional regulation of T helper cells by SMAR1.

PMID- 26220165
TI  - Induction of human IL-10-producing neutrophils by LPS-stimulated Treg cells and
      IL-10.
AB  - Recent evidence has revealed an unsuspected suppressive role played by
      neutrophils during microbial infections. An especially intriguing aspect of this
      role is the ability of neutrophils to produce interleukin (IL)-10 following
      interaction with lipopolysaccharide (LPS)-stimulated regulatory T (Treg) cells.
      The present study demonstrates that generation of IL-10 in neutrophils induced by
      LPS-stimulated Treg cells required direct cell-cell contact. This effect was
      dependent on the binding of CD11b and intercellular adhesion molecule 1. Neither
      stimulation of neutrophils with LPS nor their culture with unstimulated Treg
      cells, CD3/CD28 monoclonal antibodies-stimulated Treg cells, or T conventional
      cells affected intracellular IL-10 expression. IL-10-positive neutrophils were
      also induced by exogenous IL-10, providing an example of a positive feedback
      loop. Both LPS-stimulated Treg cells and exogenous IL-10 exclusively promoted
      posttranslational modifications of histones, H3K4me3 and H3Ac Lys4, that activate
      IL-10 genomic locus in neutrophils, while the promoter of IL-10 gene was inactive
      in resting, LPS-stimulated neutrophils, following blocking of direct interaction
      with LPS-stimulated Treg cells or in LPS-preactivated neutrophils incubated with
      LPS-stimulated Treg cells. We additionally confirmed the presence of IL-10
      producing neutrophils in vivo in patients with periodontal abscess induced by
      Gram-negative bacteria, as opposed to neutrophils isolated from the site of
      aseptic inflammation in patients with neuromyelitis optica. 

PMID- 26220166
TI  - CD161(int)CD8+ T cells: a novel population of highly functional, memory CD8+ T
      cells enriched within the gut.
AB  - The C-type lectin-like receptor CD161 is expressed by lymphocytes found in human
      gut and liver, as well as blood, especially natural killer (NK) cells, T helper
      17 (Th17) cells, and a population of unconventional T cells known as mucosal
      associated invariant T (MAIT) cells. The association of high CD161 expression
      with innate T-cell populations including MAIT cells is established. Here we show
      that CD161 is also expressed, at intermediate levels, on a prominent subset of
      polyclonal CD8+ T cells, including antiviral populations that display a memory
      phenotype. These memory CD161(int)CD8+ T cells are enriched within the colon and
      express both CD103 and CD69, markers associated with tissue residence.
      Furthermore, this population was characterized by enhanced polyfunctionality,
      increased levels of cytotoxic mediators, and high expression of the transcription
      factors T-bet and eomesodermin (EOMES). Such populations were induced by novel
      vaccine strategies based on adenoviral vectors, currently in trial against
      hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal,
      polyfunctional tissue-homing CD8+ T-cell populations in humans. As induction of
      such responses represents a major aim of T-cell prophylactic and therapeutic
      vaccines in viral disease and cancer, analysis of these populations could be of
      value in the future. 

PMID- 26220167
TI  - Regulatory T-cell depletion in the gut caused by integrin beta7 deficiency
      exacerbates DSS colitis by evoking aberrant innate immunity.
AB  - Integrin alpha4beta7 controls lymphocyte trafficking into the gut and has
      essential roles in inflammatory bowel disease (IBD). The alpha4beta7-blocking
      antibody vedolizumab is approved for IBD treatment; however, high dose of
      vedolizumab aggravates colitis in a small percentage of patients. Herein, we show
      that integrin beta7 deficiency results in colonic regulatory T (Treg) cell
      depletion and exacerbates dextran sulfate sodium (DSS) colitis by evoking
      aberrant innate immunity. In DSS-treated beta7-deficient mice, the loss of
      colonic Treg cells induces excessive macrophage infiltration in the colon via
      upregulation of colonic epithelial intercellular adhesion molecule 1 and
      increases proinflammatory cytokine expression, thereby exacerbating DSS-induced
      colitis. Moreover, reconstitution of the colonic Treg cell population in beta7
      deficient mice suppresses aberrant innate immune response in the colon and
      attenuates DSS colitis. Thus, integrin alpha4beta7 is essential for suppression
      of DSS colitis as it regulates the colonic Treg cell population and innate
      immunity. 

PMID- 26220168
TI  - Hypoxia-inducible factor 1 in dendritic cells is crucial for the activation of
      protective regulatory T cells in murine colitis.
AB  - Dendritic cells (DCs) serve as a bridge between innate and adaptive immunity and
      help to maintain intestinal homeostasis. Inflammatory bowel disease (IBD) is
      associated with dysregulation of the mucosal immune response. The concomitant
      hypoxic inflammation in IBD will activate the transcription factor hypoxia
      inducible factor-1 (HIF-1) to also drive gene expression in DCs. Recent studies
      have described a protective role for epithelial HIF-1 in mouse models of IBD. We
      investigated the role of HIF-1 in DC function in a dextran sodium sulfate (DSS)
      induced model of murine colitis. Wild-type and dendritic cell-specific HIF-1alpha
      knockout mice were treated with 3% DSS for 7 days. Knockout of HIF-1alpha in DCs
      led to a significantly larger loss of body weight in mice with DSS-induced
      colitis than in control mice. Knockout mice exhibited more severe intestinal
      inflammation with increased levels of proinflammatory cytokines and enhanced
      production of mucin. Induction of regulatory T cells (Tregs) was impaired, and
      the number of forkhead box P3 (Foxp3) Tregs was diminished by dendritic HIF
      1alpha knockout. Our findings demonstrate that in DCs HIF-1alpha is necessary for
      the induction of sufficient numbers of Tregs to control intestinal inflammation. 

PMID- 26220169
TI  - Vitamin D status of Icelandic children and its influence on bone accrual.
AB  - The importance of vitamin D for children's bone health has been well established,
      but the effects of less severe deficiency are not fully known. The main objective
      of this study was to assess the vitamin D status of Icelandic children at the age
      of 7, and again at 9 years of age, and the association of vitamin D status with
      bone mineral content and bone accrual over 2 years. We invited 321 children to
      participate in this study, and 267 (83 %) took part; 211 (79 %) underwent a DXA
      scan and 164 were again scanned 2 years later; 159 (60 %) vitamin D samples were
      measured and 119 (75 %) were measured again 2 years later. At age 7, 65 % of the
      children had vitamin D concentrations <50 nmol/l, and at age 9 this figure was 60
      %. At age 7, 43 % of the children had insufficient amounts of vitamin D (37.5-50
      nmol/l), and 22 % had a vitamin D deficiency (<37.5 nmol/l). In linear regression
      analysis, no association was found between vitamin D and bone mineral content.
      Furthermore, there was no significant difference in bone accrual over 2 years for
      the children with insufficient or deficient vitamin D at both ages, compared to
      those having more than 50 nmol/l at both time points. More than 60 % of Icelandic
      children have inadequate concentrations of vitamin D in serum repeatedly over a 2
      year interval. However, vitamin D in the range did not have a significant effect
      on bone mineral content or accrual at ages 7 and 9. 

PMID- 26220170
TI  - Dissolution Engineering of Platinum Alloy Counter Electrodes in Dye-Sensitized
      Solar Cells.
AB  - The dissolution of platinum (Pt) has been one of the heart issues in developing
      advanced dye-sensitized solar cells (DSSCs). We present here the experimental
      realization of stable counter-electrode (CE) electrocatalysts by alloying Pt with
      transition metals for enhanced dissolution resistance to state-of-the-art
      iodide/triiodide (I(-)/I3(-)) redox electrolyte. Our focus is placed on the
      systematic studies of dissolution engineering for PtM0.05 (M=Ni, Co, Fe, Pd, Mo,
      Cu, Cr, and Au) alloy CE electrocatalysts along with mechanism analysis from
      thermodynamical aspects, yielding more negative Gibbs free energies for the
      dissolution reactions of transition metals. The competitive reactions between
      transition metals with iodide species (I3(-), I2) could protect the Pt atoms from
      being dissolved by redox electrolyte and therefore remain the high catalytic
      activity of the Pt electrode.

PMID- 26220171
TI  - Developmental effects of wheel running on hippocampal glutamate receptor
      expression in young and mature adult rats.
AB  - Recent evidence suggests that the behavioral benefits associated with voluntary
      wheel running in rodents may be due to modulation of glutamatergic transmission
      in the hippocampus, a brain region implicated in learning and memory. However,
      the expression of the glutamatergic ionotropic N-methyl-d-aspartate receptor
      (GluN) in the hippocampus in response to chronic sustained voluntary wheel
      running has not yet been investigated. Further, the developmental effects during
      young and mature adulthood on wheel running output and GluN expression in
      hippocampal subregions has not been determined, and therefore is the main focus
      of this investigation. Eight-week-old and 16-week-old male Wistar rats were
      housed in home cages with free access to running wheels and running output was
      monitored for 4weeks. Wheel access was terminated and tissues from the dorsal and
      ventral hippocampi were processed for Western blot analysis of GluN subunit
      expression. Young adult runners demonstrated an escalation in running output but
      this behavior was not evident in mature adult runners. In parallel, young adult
      runners demonstrated a significant increase in total GluN (1 and 2A) subunit
      expression in the dorsal hippocampus (DH), and an opposing effect in the ventral
      hippocampus (VH) compared to age-matched sedentary controls; these changes in
      total protein expression were not associated with significant alterations in the
      phosphorylation of the GluN subunits. In contrast, mature adult runners
      demonstrated a reduction in total GluN2A expression in the DH, without producing
      alterations in the VH compared to age-matched sedentary controls. In conclusion,
      differential running activity-mediated modulation of GluN subunit expression in
      the hippocampal subregions was revealed to be associated with developmental
      effects on running activity, which may contribute to altered hippocampal synaptic
      activity and behavioral outcomes in young and mature adult subjects. 

PMID- 26220172
TI  - Acute and subchronic in-vivo effects of Ferula hermonis L. and Sambucus nigra L.
      and their potential active isolates in a diabetic mouse model of neuropathic
      pain.
AB  - BACKGROUND: The prevalence of Diabetes mellitus (DM) is escalating rapidly
      worldwide, and associated with micro- and macrovascular complications. Diabetic
      neuropathy (DN) is a common complication of DM, and has a few approved therapies
      with limited efficacy and several side-effects. Herbal medicine is used worldwide
      as an effective alternative-medicine. The present study aims to investigate the
      activities of Ferula hermonis Boiss. EtAc (Ferula) and Sambucus nigra L. aqueous
      (Elder) extracts, and their potential active isolates; for acute (6 h) and
      subchronic (8 days) glucose homeostasis, in vivo antioxidant potential and DN
      amelioration in alloxan-induced DM mice model. METHODS: DM was induced
      experimentally by injection of freshly prepared alloxan every 48-h for three
      times at a dose of 180 mg/kg. Utilizing tail-flick, hot-plate latencies
      (accessing thermal hyperalgesia) and von Frey filaments test (accessing tactile
      allodynia), DN was evaluated for longer period of time (8 weeks). RESULTS: The
      most active isolates from Ferula was ferutinin, and Kaempferol from Elder
      utilizing bio-guided fractionation and RP-HPLC steeping methods. Compared to
      glibenclamide (GB) and tramadol (TRA), as positive controls, the highest doses of
      tested compounds exerted remarkable hypoglycemic and antinociceptive activities.
      The best acute hypoglycemic effect was observed with ferutinin (1.4 folds more
      effective than GB). Elder has shown the best subchronic hypoglycemic effect (2.6
      folds more effective than GB) and the greatest efficacy against tactile allodynia
      following a single-administration, yet required repeated administration for
      improvement of thermal hyperalgesia. CONCLUSIONS: Without the use-limiting-side
      effects of existing therapies, Ferula, Elder and their active isolates have shown
      significant results in ameliorating DM and long standing diabetes-induced
      complications.

PMID- 26220173
TI  - Novel mitochondrial protein interactors of immunoglobulin light chains causing
      heart amyloidosis.
AB  - In immunoglobulin (Ig) light-chain (LC) (AL) amyloidosis, AL deposition
      translates into life-threatening cardiomyopathy. Clinical and experimental
      evidence indicates that soluble cardiotoxic LCs are themselves harmful for cells,
      by which they are internalized. Hypothesizing that interaction of soluble
      cardiotoxic LCs with cellular proteins contributes to damage, we characterized
      their interactome in cardiac cells. LCs were purified from patients with AL
      amyloidosis cardiomyopathy or multiple myeloma without amyloidosis (the
      nonamyloidogenic/noncardiotoxic LCs served as controls) and employed at
      concentrations in the range observed in AL patients' sera. A functional proteomic
      approach, based on direct and inverse coimmunoprecipitation and mass
      spectrometry, allowed identifying LC-protein complexes. Findings were validated
      by colocalization, fluorescence lifetime imaging microscopy (FLIM)-fluorescence
      resonance energy transfer (FRET), and ultrastructural studies, using human
      primary cardiac fibroblasts (hCFs) and stem cell-derived cardiomyocytes.
      Amyloidogenic cardiotoxic LCs interact in vitro with specific intracellular
      proteins involved in viability and metabolism. Imaging confirmed that, especially
      in hCFs, cardiotoxic LCs (not controls) colocalize with mitochondria and
      spatially associate with selected interactors: mitochondrial optic atrophy 1-like
      protein and peroxisomal acyl-coenzyme A oxidase 1 (FLIM-FRET efficiencies 11 and
      6%, respectively). Cardiotoxic LC-treated hCFs display mitochondrial
      ultrastructural changes, supporting mitochondrial involvement. We show that
      cardiotoxic LCs establish nonphysiologic protein-protein contacts in human
      cardiac cells, offering new clues on the pathogenesis of AL cardiomyopathy.

PMID- 26220174
TI  - Loss of long-chain acyl-CoA synthetase isoform 1 impairs cardiac autophagy and
      mitochondrial structure through mechanistic target of rapamycin complex 1
      activation.
AB  - Because hearts with a temporally induced knockout of acyl-CoA synthetase 1
      (Acsl1(T-/-)) are virtually unable to oxidize fatty acids, glucose use increases
      8-fold to compensate. This metabolic switch activates mechanistic target of
      rapamycin complex 1 (mTORC1), which initiates growth by increasing protein and
      RNA synthesis and fatty acid metabolism, while decreasing autophagy. Compared
      with controls, Acsl1(T-/-) hearts contained 3 times more mitochondria with
      abnormal structure and displayed a 35-43% lower respiratory function. To study
      the effects of mTORC1 activation on mitochondrial structure and function, mTORC1
      was inhibited by treating Acsl1(T-/-) and littermate control mice with rapamycin
      or vehicle alone for 2 wk. Rapamycin treatment normalized mitochondrial
      structure, number, and the maximal respiration rate in Acsl1(T-/-) hearts, but
      did not improve ADP-stimulated oxygen consumption, which was likely caused by the
      33-51% lower ATP synthase activity present in both vehicle- and rapamycin-treated
      Acsl1(T-/-) hearts. The turnover of microtubule associated protein light chain 3b
      in Acsl1(T-/-) hearts was 88% lower than controls, indicating a diminished rate
      of autophagy. Rapamycin treatment increased autophagy to a rate that was 3.1-fold
      higher than in controls, allowing the formation of autophagolysosomes and the
      clearance of damaged mitochondria. Thus, long-chain acyl-CoA synthetase isoform 1
      (ACSL1) deficiency in the heart activated mTORC1, thereby inhibiting autophagy
      and increasing the number of damaged mitochondria.

PMID- 26220176
TI  - Intercellular transfer of transferrin receptor by a contact-, Rab8-dependent
      mechanism involving tunneling nanotubes.
AB  - Intercellular communication between cancer cells, especially between cancer and
      stromal cells, plays an important role in disease progression. We examined the
      intercellular transfer of organelles and proteins in vitro and in vivo and the
      role of tunneling nanotubes (TNTs) in this process. TNTs are membrane bridges
      that facilitate intercellular transfer of organelles of unclear origin. Using 3
      dimensional quantitative and qualitative confocal microscopy, we showed that TNTs
      contain green fluorescent protein (GFP)-early endosome antigen (EEA) 1, GFP Rab5,
      GFP Rab11, GFP Rab8, transferrin (Tf), and Tf receptor (Tf-R) fused to mCherry
      (Tf-RmCherry). Tf-RmCherry was transferred between cancer cells by a contact
      dependent but secretion-independent mechanism. Live cell imaging showed TNT
      formation preceding the transfer of Tf-RmCherry and involving the function of the
      small guanosine triphosphatase (GTPase) Rab8, which colocalized with Tf-RmCherry
      in the TNTs and was cotransferred to acceptor cells. Tf-RmCherry was transferred
      from cancer cells to fibroblasts, a noteworthy finding that suggests that this
      process occurs between tumor and stromal cells in vivo. We strengthened this
      hypothesis in a xenograft model of breast cancer using enhanced (e)GFP-expressing
      mice. Tf-RmCherry transferred from tumor to stromal cells and this process
      correlated with an increased opposite transfer of eGFP from stromal to tumor
      cells, together pointing toward complex intercellular communication at the tumor
      site.

PMID- 26220175
TI  - ATP-binding cassette transporters and sterol O-acyltransferases interact at
      membrane microdomains to modulate sterol uptake and esterification.
AB  - A key component of eukaryotic lipid homeostasis is the esterification of sterols
      with fatty acids by sterol O-acyltransferases (SOATs). The esterification
      reactions are allosterically activated by their sterol substrates, the majority
      of which accumulate at the plasma membrane. We demonstrate that in yeast, sterol
      transport from the plasma membrane to the site of esterification is associated
      with the physical interaction of the major SOAT, acyl-coenzyme A:cholesterol
      acyltransferase (ACAT)-related enzyme (Are)2p, with 2 plasma membrane ATP-binding
      cassette (ABC) transporters: Aus1p and Pdr11p. Are2p, Aus1p, and Pdr11p, unlike
      the minor acyltransferase, Are1p, colocalize to sterol and sphingolipid-enriched,
      detergent-resistant microdomains (DRMs). Deletion of either ABC transporter
      results in Are2p relocalization to detergent-soluble membrane domains and a
      significant decrease (53-36%) in esterification of exogenous sterol. Similarly,
      in murine tissues, the SOAT1/Acat1 enzyme and activity localize to DRMs. This
      subcellular localization is diminished upon deletion of murine ABC transporters,
      such as Abcg1, which itself is DRM associated. We propose that the close
      proximity of sterol esterification and transport proteins to each other combined
      with their residence in lipid-enriched membrane microdomains facilitates rapid,
      high-capacity sterol transport and esterification, obviating any requirement for
      soluble intermediary proteins.

PMID- 26220177
TI  - India unlikely to meet goal of eliminating kala-azar by 2015, say experts.

PMID- 26220178
TI  - Management of non-gonococcal urethritis.
AB  - Non-gonococcal urethritis (NGU), or inflammation of the urethra, is the most
      common treatable sexually transmitted syndrome in men, with approximately 20-50 %
      of cases being due to infection with Chlamydia trachomatis and 10-30 % Mycoplasma
      genitalium. Other causes are Ureaplasma urealyticum, Trichomonas vaginalis,
      anaerobes, Herpes simplex virus (HSV) and adenovirus. Up to half of the cases are
      non-specific. Urethritis is characterized by discharge, dysuria and/or urethral
      discomfort but may be asymptomatic. The diagnosis of urethritis is confirmed by
      demonstrating an excess of polymorpho-nuclear leucocytes (PMNLs) in a stained
      smear. An excess of mononuclear leucocytes in the smear indicates a viral
      etiology. In patients presenting with symptoms of urethritis, the diagnosis
      should be confirmed by microscopy of a stained smear, ruling out gonorrhea.
      Nucleid acid amplifications tests (NAAT) for Neisseria gonorrhoeae, C.
      trachomatis and for M. genitalium. If viral or protozoan aetiology is suspected,
      NAAT for HSV, adenovirus and T. vaginalis, if available. If marked symptoms and
      urethritis is confirmed, syndromic treatment should be given at the first
      appointment without waiting for the laboratory results. Treatment options are
      doxycycline 100 mg x 2 for one week or azithromycin 1 gram single dose or 1,5
      gram distributed in five days. However, azithromycin as first line treatment
      without test of cure for M. genitalium and subsequent Moxifloxacin treatment of
      macrolide resistant strains will select and increase the macrolide resistant
      strains in the population. If positive for M. genitalium, test of cure samples
      should be collected no earlier than three weeks after start of treatment. If
      positive in test of cure, moxifloxacin 400 mg 7-14 days is indicated. Current
      partner(s) should be tested and treated with the same regimen. They should
      abstain from intercourse until both have completed treatment. Persistent or
      recurrent NGU must be confirmed with microscopy. Reinfection and compliance must
      be considered. Evidence for the following recommendations is limited, and is
      based on clinical experience and guidelines. If doxycycline was given as first
      therapy, azithromycin five days plus metronidazole 4-500 mg twice daily for 5-7
      days should be given. If azithromycin was prescribed as first therapy,
      doxycycline 100 mg x 2 for one week plus metronidazole, or moxifloxacin 400 mg
      orally once daily for 7-14 days should be given.

PMID- 26220179
TI  - Effects of Kinesio Tape application to quadriceps muscles on isokinetic muscle
      strength, gait, and functional parameters in patients with stroke.
AB  - The aim of this study was to evaluate the effects of Kinesio Tape (KT)
      application to quadriceps muscles on isokinetic muscle strength, gait, and
      functional parameters in patients with stroke. Twenty-four patients were
      allocated into KT and control groups. All patients participated in the same
      conventional rehabilitation program 5 times/wk for 4 wk. In addition, KT was
      applied to quadriceps muscles bilaterally to the patients in the KT group.
      Compared with baseline, peak torque levels increased significantly in both groups
      (all p < 0.05). However, change levels were significantly higher in the KT group
      than the control group at 60 degrees/second angular velocity (AV) in extension (p
      = 0.04) and 60 and 180 degrees/second AV in flexion (both p = 0.02) on the
      paretic side. Moreover, the change levels were more prominent in the KT group at
      60 and 180 degrees/second AV in extension (p = 0.03 and p = 0.04, respectively)
      on the nonparetic side. Gait, balance, mobility, and quality of life values
      improved significantly in both groups (all p < 0.05), yet the change levels
      between the groups did not reach significance (p > 0.05). KT application to
      quadriceps muscles in addition to conventional exercises for 4 wk is effective on
      isokinetic but not functional parameters. 

PMID- 26220180
TI  - Nucleotide binding interactions modulate dNTP selectivity and facilitate 8-oxo
      dGTP incorporation by DNA polymerase lambda.
AB  - 8-Oxo-7,8,-dihydro-2'-deoxyguanosine triphosphate (8-oxo-dGTP) is a major product
      of oxidative damage in the nucleotide pool. It is capable of mispairing with
      adenosine (dA), resulting in futile, mutagenic cycles of base excision repair.
      Therefore, it is critical that DNA polymerases discriminate against 8-oxo-dGTP at
      the insertion step. Because of its roles in oxidative DNA damage repair and non
      homologous end joining, DNA polymerase lambda (Pol lambda) may frequently
      encounter 8-oxo-dGTP. Here, we have studied the mechanisms of 8-oxo-dGMP
      incorporation and discrimination by Pol lambda. We have solved high resolution
      crystal structures showing how Pol lambda accommodates 8-oxo-dGTP in its active
      site. The structures indicate that when mispaired with dA, the oxidized
      nucleotide assumes the mutagenic syn-conformation, and is stabilized by multiple
      interactions. Steady-state kinetics reveal that two residues lining the dNTP
      binding pocket, Ala(510) and Asn(513), play differential roles in dNTP
      selectivity. Specifically, Ala(510) and Asn(513) facilitate incorporation of 8
      oxo-dGMP opposite dA and dC, respectively. These residues also modulate the
      balance between purine and pyrimidine incorporation. Our results shed light on
      the mechanisms controlling 8-oxo-dGMP incorporation in Pol lambda and on the
      importance of interactions with the incoming dNTP to determine selectivity in
      family X DNA polymerases. 

PMID- 26220181
TI  - DNA polymerases kappa and zeta cooperatively perform mutagenic translesion
      synthesis of the C8-2'-deoxyguanosine adduct of the dietary mutagen IQ in human
      cells.
AB  - The roles of translesion synthesis (TLS) DNA polymerases in bypassing the C8-2'
      deoxyguanosine adduct (dG-C8-IQ) formed by 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ), a highly mutagenic and carcinogenic heterocyclic amine found in
      cooked meats, were investigated. Three plasmid vectors containing the dG-C8-IQ
      adduct at the G1-, G2- or G3-positions of the NarI site (5'-G1G2CG3CC-3') were
      replicated in HEK293T cells. Fifty percent of the progeny from the G3 construct
      were mutants, largely G->T, compared to 18% and 24% from the G1 and G2
      constructs, respectively. Mutation frequency (MF) of dG-C8-IQ was reduced by 38
      67% upon siRNA knockdown of pol kappa, whereas it was increased by 10-24% in pol
      eta knockdown cells. When pol kappa and pol zeta were simultaneously knocked
      down, MF of the G1 and G3 constructs was reduced from 18% and 50%, respectively,
      to <3%, whereas it was reduced from 24% to <1% in the G2 construct. In vitro TLS
      using yeast pol zeta showed that it can extend G3*:A pair more efficiently than
      G3*:C pair, but it is inefficient at nucleotide incorporation opposite dG-C8-IQ.
      We conclude that pol kappa and pol zeta cooperatively carry out the majority of
      the error-prone TLS of dG-C8-IQ, whereas pol eta is involved primarily in its
      error-free bypass. 

PMID- 26220183
TI  - Dissecting the target specificity of RNase H recruiting oligonucleotides using
      massively parallel reporter analysis of short RNA motifs.
AB  - Processing and post-transcriptional regulation of RNA often depend on binding of
      regulatory molecules to short motifs in RNA. The effects of such interactions are
      difficult to study, because most regulatory molecules recognize partially
      degenerate RNA motifs, embedded in a sequence context specific for each RNA.
      Here, we describe Library Sequencing (LibSeq), an accurate massively parallel
      reporter method for completely characterizing the regulatory potential of
      thousands of short RNA sequences in a specific context. By sequencing cDNA
      derived from a plasmid library expressing identical reporter genes except for a
      degenerate 7mer subsequence in the 3'UTR, the regulatory effects of each 7mer can
      be determined. We show that LibSeq identifies regulatory motifs used by RNA
      binding proteins and microRNAs. We furthermore apply the method to cells
      transfected with RNase H recruiting oligonucleotides to obtain quantitative
      information for >15000 potential target sequences in parallel. These
      comprehensive datasets provide insights into the specificity requirements of
      RNase H and allow a specificity measure to be calculated for each tested
      oligonucleotide. Moreover, we show that inclusion of chemical modifications in
      the central part of an RNase H recruiting oligonucleotide can increase its
      sequence-specificity. 

PMID- 26220182
TI  - Identification of siRNA delivery enhancers by a chemical library screen.
AB  - Most delivery systems for small interfering RNA therapeutics depend on
      endocytosis and release from endo-lysosomal compartments. One approach to improve
      delivery is to identify small molecules enhancing these steps. It is unclear to
      what extent such enhancers can be universally applied to different delivery
      systems and cell types. Here, we performed a compound library screen on two well
      established siRNA delivery systems, lipid nanoparticles and cholesterol
      conjugated-siRNAs. We identified fifty-one enhancers improving gene silencing 2-5
      fold. Strikingly, most enhancers displayed specificity for one delivery system
      only. By a combination of quantitative fluorescence and electron microscopy we
      found that the enhancers substantially differed in their mechanism of action,
      increasing either endocytic uptake or release of siRNAs from endosomes.
      Furthermore, they acted either on the delivery system itself or the cell, by
      modulating the endocytic system via distinct mechanisms. Interestingly, several
      compounds displayed activity on different cell types. As proof of principle, we
      showed that one compound enhanced siRNA delivery in primary endothelial cells in
      vitro and in the endocardium in the mouse heart. This study suggests that a
      pharmacological approach can improve the delivery of siRNAs in a system-specific
      fashion, by exploiting distinct mechanisms and acting upon multiple cell types. 

PMID- 26220184
TI  - Interaction of Formulation and Device Factors Determine the In Vitro Performance
      of Salbutamol Sulphate Dry Powders for Inhalation.
AB  - A variety of capsule-based dry powder inhalers were used to evaluate formulation
      device interaction. The in vitro deposition of salbutamol sulphate (SS) was
      compared directly to published data for salmeterol xinafoate (SX). A 3(2)
      factorial design was used to assess the effect of SS formulations with three
      blends of different grade coarse lactose supplemented with different levels of
      fine lactose. These formulations were tested for homogeneity and evaluated for
      their in vitro deposition using Aeroliser, Handihaler and Rotahaler devices. The
      performance of the SS-lactose formulations differed across the grade of lactose
      and amount of fine lactose used compared to the same powder compositions blended
      with SX. SX had a greater fine particle fraction than SS for most of the
      comparable formulations, probably because of the different cohesiveness of the
      drugs. A head-to-head comparison of 'matched' SX and SS formulations when
      aerosolised from the same three devices demonstrated that formulation-device
      interactions are as critical in determining the in vitro deposition of drug
      lactose blends as the identity of the active pharmaceutical ingredient. This work
      has revealed the limitations of the interpretative value of published in vitro
      performance data generated with a single device (even at equivalent
      aerosolisation force), when designing formulations for a different device.

PMID- 26220185
TI  - Jeanette's feast.

PMID- 26220186
TI  - 'Cloud computing' and clinical trials: report from an ECRIN workshop.
AB  - Growing use of cloud computing in clinical trials prompted the European Clinical
      Research Infrastructures Network, a European non-profit organisation established
      to support multinational clinical research, to organise a one-day workshop on the
      topic to clarify potential benefits and risks. The issues that arose in that
      workshop are summarised and include the following: the nature of cloud computing
      and the cloud computing industry; the risks in using cloud computing services
      now; the lack of explicit guidance on this subject, both generally and with
      reference to clinical trials; and some possible ways of reducing risks. There was
      particular interest in developing and using a European 'community cloud'
      specifically for academic clinical trial data. It was recognised that the day
      long workshop was only the start of an ongoing process. Future discussion needs
      to include clarification of trial-specific regulatory requirements for cloud
      computing and involve representatives from the relevant regulatory bodies. 

PMID- 26220187
TI  - Qipengyuania sediminis gen. nov., sp. nov., a member of the family
      Erythrobacteraceae isolated from subterrestrial sediment.
AB  - A Gram-reaction-negative, non-motile, facultatively aerobic bacterium, designated
      strain M1T, was isolated from a subterrestrial sediment sample of Qiangtang Basin
      in Qinghai-Tibetan plateau, China. The strain formed rough yellow colonies on R2A
      plates. Cells were oval or short rod-shaped, catalase-positive and oxidase
      negative. Phylogenetic analyses based on 16S rRNA gene sequences indicated that
      the isolate belonged to the family Erythrobacteraceae and showed 96.2-96.4 % 16S
      rRNA gene sequence similarities to its closest relatives. Chemotaxonomic analysis
      revealed ubiquinone-10 (Q10) as the dominant respiratory quinone of strain M1T
      and C17 : 1omega6c (44.2 %) and C18 : 1omega7c (13.7 %) as the major fatty acids.
      The major polar lipids were phosphatidylethanolamine, phosphatidylcholine,
      phosphatidylglycerol, diphosphatidylglycerol, sphingoglycolipid, three
      unidentified glycolipids, one unidentified phosphoglycolipid and one unidentified
      lipid. The DNA G+C content of strain M1T was 73.7 mol%. On the basis of
      phenotypic, phylogenetic and genotypic data presented in this study, strain M1T
      represents a novel species of a new genus in the family Erythrobacteraceae, for
      which the name Qipengyuania sediminis gen. nov., sp. nov. is proposed. The type
      strain of the type species is M1T ( = CGMCC 1.12928T = JCM 30182T).

PMID- 26220189
TI  - Changes in central corneal thickness and refractive error after thin-flap laser
      in situ keratomileusis in Chinese eyes.
AB  - BACKGROUND: Refractive stability is influenced by alterations in corneal
      curvature and corneal thickness after laser in situ keratomileusis (LASIK). The
      aim of this study was to analyze the changes of central corneal thickness (CCT)
      and refractive error following thin-flap LASIK surgery in Chinese eyes. METHODS:
      One hundred and fifty-eight myopic patients (302 eyes) who underwent thin-flap
      LASIK surgery were prospectively evaluated. CCT was measured by non-contact
      specular microscopy before, and 1 day, 1 week, and 1, 3, and 6 months following
      surgery. Age, refractive error, and optic zone diameter were also recorded.
      RESULTS: Preoperatively, the mean CCT was 531.6 +/- 24.3 MUm. At 1 day, 1 week,
      and 1, 3, and 6 months after surgery, mean CCTs were 431.4 +/- 38.4 MUm, 422.6 +/
      3 7.8 MUm, 427.2 +/- 38.0 MUm, 434.4 +/- 38.2 MUm, and 435.6 +/- 38.0 MUm,
      respectively. Significant changes were detected in CCT values at each time point
      after thin-flap LASIK treatment (P < 0.05). The mean preoperative spherical
      equivalent (SE) was -5.73 +/- 2.30 diopters (D). At 1 day, 1 week, and 1, 3, and
      6 months after surgery, it was 0.26 +/- 0.58 D, 0.54 +/- 0.52 D, 0.49 +/- 0.53 D,
      0.45 +/- 0.49 D, and 0.37 +/- 0.42 D, respectively. The spherical equivalent
      refraction at 6 months postsurgery was close to the predicted value (0.34 +/-
      0.30 D). The changes in CCT within 6 months (4.06 +/- 9.99 MUm) were negatively
      correlated with age, preoperative refractive error, and optical zone diameter,
      respectively (r = -0.180, P < 0.05; r = -0.187, P < 0.001; r = -0.171, P < 0.05,
      respectively). No significant correlation was found between CCT changes and SE
      changes at different time points, postoperatively. CONCLUSIONS: CCTs decreased
      significantly at 1 day after surgery, and continued to decline at 1 week after
      surgery, then increased over time. From postoperative 1 week, SE over time
      continually shifted to the myopic side.

PMID- 26220188
TI  - Network analysis of temporal functionalities of the gut induced by perturbations
      in new-born piglets.
AB  - BACKGROUND: Evidence is accumulating that perturbation of early life microbial
      colonization of the gut induces long-lasting adverse health effects in
      individuals. Understanding the mechanisms behind these effects will facilitate
      modulation of intestinal health. The objective of this study was to identify
      biological processes involved in these long lasting effects and the (molecular)
      factors that regulate them. We used an antibiotic and the same antibiotic in
      combination with stress on piglets as an early life perturbation. Then we used
      host gene expression data from the gut (jejunum) tissue and community-scale
      analysis of gut microbiota from the same location of the gut, at three different
      time-points to gauge the reaction to the perturbation. We analysed the data by a
      new combination of existing tools. First, we analysed the data in two dimensions,
      treatment and time, with quadratic regression analysis. Then we applied network
      based data integration approaches to find correlations between host gene
      expression and the resident microbial species. RESULTS: The use of a new
      combination of data analysis tools allowed us to identify significant long
      lasting differences in jejunal gene expression patterns resulting from the early
      life perturbations. In addition, we were able to identify potential key gene
      regulators (hubs) for these long-lasting effects. Furthermore, data integration
      also showed that there are a handful of bacterial groups that were associated
      with temporal changes in gene expression. CONCLUSION: The applied systems-biology
      approach allowed us to take the first steps in unravelling biological processes
      involved in long lasting effects in the gut due to early life perturbations. The
      observed data are consistent with the hypothesis that these long lasting effects
      are due to differences in the programming of the gut immune system as induced by
      the temporary early life changes in the composition and/or diversity of
      microbiota in the gut.

PMID- 26220191
TI  - A new variant of cytolethal distending toxin in a clinical isolate of
      Campylobacter hyointestinalis.
AB  - Increasing numbers of Campylobacter hyointestinalis have been isolated from
      humans and animals with gastroenteritis, although the virulence mechanism of this
      species remains largely unknown. Here, we show that C. hyointestinalis isolated
      from a patient with diarrhoea in Thailand produced a novel variant of cytolethal
      distending toxin (CDT). Sequencing of a 13 965 bp genomic region of C.
      hyointestinalis carrying the genes coding for Ch-CDT revealed three ORFs of 798,
      804 and 537 bp, which code for the Ch-CdtA, Ch-CdtB and Ch-CdtC subunits,
      respectively. The deduced amino acid sequence of Ch-CdtA showed ~38.9 % homology
      with the CdtA of Campylobacter coli, but sequences of Ch-CdtB and Ch-CdtC were
      homologous to CdtB (65.7 %) and CdtC (33.1 %) of Campylobacter upsaliensis,
      respectively. Filter-sterilized sonic lysate of C. hyointestinalis demonstrated
      distension and death of HeLa cells by arresting the cell cycle at the G(2)/M
      phase and phosphorylation of host histone H2AX, a sensitive marker of DNA double
      strand breaks. Rabbit antiserum raised against recombinant Ch-CdtB was not
      reactive against the recombinant CdtB protein of Campylobacter jejuni. A
      reconstituted Ch-CDT holotoxin prepared using each of the recombinant subunit
      proteins demonstrated distension and death of HeLa cells, suggesting that the C.
      hyointestinalis isolate indeed produced functionally active Ch-CDT. Furthermore,
      the immunological distinctiveness of the Ch-CDT produced by C. hyointestinalis
      and the increasing prevalence of the species in patients and animals with
      gastroenteritis suggest that this species may be an important emerging zoonotic
      pathogen.

PMID- 26220190
TI  - Tuberous sclerosis complex neuropathology requires glutamate-cysteine ligase.
AB  - INTRODUCTION: Tuberous sclerosis complex (TSC) is a genetic disease resulting
      from mutation in TSC1 or TSC2 and subsequent hyperactivation of mammalian Target
      of Rapamycin (mTOR). Common TSC features include brain lesions, such as cortical
      tubers and subependymal giant cell astrocytomas (SEGAs). However, the current
      treatment with mTOR inhibitors has critical limitations. We aimed to identify new
      targets for TSC pharmacotherapy. RESULTS: The results of our shRNA screen point
      to glutamate-cysteine ligase catalytic subunit (GCLC), a key enzyme in
      glutathione synthesis, as a contributor to TSC-related phenotype. GCLC inhibition
      increased cellular stress and reduced mTOR hyperactivity in TSC2-depleted neurons
      and SEGA-derived cells. Moreover, patients' brain tubers showed elevated GCLC and
      stress markers expression. Finally, GCLC inhibition led to growth arrest and
      death of SEGA-derived cells. CONCLUSIONS: We describe GCLC as a part of redox
      adaptation in TSC, needed for overgrowth and survival of mutant cells, and
      provide a potential novel target for SEGA treatment.

PMID- 26220193
TI  - Stereoselective synthesis of activated 2-arylazetidines via imino-aldol reaction.
AB  - A simple and efficient synthetic route to substituted N-sulfinyl and N-sulfonyl
      azetidines is described involving imino-aldol reaction of ester enolates with
      racemic and non-racemic aldimines for obtaining beta-amino esters as a key step.
      These beta-amino esters on subsequent reduction followed by TsCl/KOH mediated
      cyclization produced the corresponding racemic and non-racemic azetidines with
      high yield and stereoselectivity. 

PMID- 26220192
TI  - Impact of nasoseptal flap elevation on sinonasal quality of life in endoscopic
      endonasal approach to pituitary adenomas.
AB  - To evaluate the impact of nasoseptal flap (NSF) elevation on sinonasal quality of
      life (QOL) in patients with pituitary adenomas who underwent endoscopic endonasal
      trans-sphenoidal approach (EETSA), the data of 106 eligible patients were
      included from February 2011 to December 2014. The scores of Sinonasal Outcome
      Test (SNOT-22) Questionnaire were assessed in case (that received reconstruction
      with NSF) and control groups preoperatively as well as 1, 3, 6, and more than 12
      months postoperatively. Nine most related sinonasal questions were evaluated
      separately (9Q). There were no significant inter-group differences in the mean
      SNOT-22, 9Q, and sense of taste/smell scores in preoperative and all
      postoperative assessments. Within each group, a significant improvement of SNOT
      22 and 9Q scores were noted after 12 months of surgery compared to preoperative
      data. In the NSF group, comparison of the pre- and first postoperative evaluation
      revealed a significant deterioration in 9Q score (p = 0.007) and "sense of
      taste/smell" (p < 0.001) which both returned to baseline in the 3rd month.
      Patients who used nasal paper mask for more than 100 "hour-days" showed a better
      SNOT-22 scores at 1st (p = 0.04) and 3rd (p < 0.001) months after surgery.
      Patients with adrenocorticotropic hormone (ACTH) secretory adenomas showed
      significantly higher scores of SNOT-22 in all postoperative assessments compared
      to the others. Although nasal symptoms deteriorated at first postoperative month
      (compare to preoperative data) in the NSF group, no negative impacts on the
      sinonasal QOL was showed comparing to the control group. ACTH-secreting adenomas
      could be assumed as a risk factor for poorer sinonasal QOL in EETSA.

PMID- 26220194
TI  - A facile one-pot synthesis of blue and red luminescent thiol stabilized gold
      nanoclusters: a thorough optical and microscopy study.
AB  - Here in this contribution, blue and red luminescent 1-dodecanethiol (DT)
      terminated gold nanoclusters (AuNC) were prepared by a simple two-step synthesis
      route where the first step involved the surfactant-free synthesis of bare AuNC in
      N,N'-dimethylformamide (DMF) and the second step is the termination of the as
      prepared bare AuNC by 1-dodecanethiol. The blue and red luminescent DT-terminated
      AuNC were isolated by a solvent-induced precipitation followed by an ultra
      centrifugation technique. Both the bare AuNC and the blue and red luminescent DT
      terminated AuNC exhibit stable photoluminescence and good solubility in various
      solvents. The photo-physical, electronic, structural, and morphological
      properties of the bare AuNC and the blue and red luminescent DT-terminated AuNC
      were examined by performing UV-Vis absorption spectroscopy, stationary and time
      resolved PL spectroscopy, X-ray photoelectron spectroscopy (XPS), femtosecond
      transient absorption spectroscopy, Fourier-transform infrared spectroscopy (FTIR
      ATR), and high-resolution transmission electron microscopy (HRTEM) experiments. 

PMID- 26220195
TI  - Allelic mutations in noncoding genomic sequences construct novel transcription
      factor binding sites that promote gene overexpression.
AB  - The growth and survival factor hepatocyte growth factor (HGF) is expressed at
      high levels in multiple myeloma (MM) cells. We report here that elevated HGF
      transcription in MM was traced to DNA mutations in the promoter alleles of HGF.
      Sequence analysis revealed a previously undiscovered single-nucleotide
      polymorphism (SNP) and crucial single-nucleotide variants (SNVs) in the promoters
      of myeloma cells that produce large amounts of HGF. The allele-specific mutations
      functionally reassembled wild-type sequences into the motifs that affiliate with
      endogenous transcription factors NFKB (nuclear factor kappa-B), MZF1 (myeloid
      zinc finger 1), and NRF-2 (nuclear factor erythroid 2-related factor 2). In
      vitro, a mutant allele that gained novel NFKB-binding sites directly responded to
      transcriptional signaling induced by tumor necrosis factor alpha (TNFalpha) to
      promote high levels of luciferase reporter. Given the recent discovery by genome
      wide sequencing (GWS) of numerous non-coding mutations in myeloma genomes, our
      data provide evidence that heterogeneous SNVs in the gene regulatory regions may
      frequently transform wild-type alleles into novel transcription factor binding
      properties to aberrantly interact with dysregulated transcriptional signals in MM
      and other cancer cells.

PMID- 26220196
TI  - Combined use of probucol and cilostazol with atorvastatin attenuates
      atherosclerosis in moderately hypercholesterolemic rabbits.
AB  - BACKGROUND: Atherosclerotic cardiovascular disease is one of the major diseases
      that seriously impacts human health. Combined drug therapy may be efficacious in
      delaying the occurrence of cardiovascular events. AIM: The current study was
      designed to investigate whether combined use of probucol (an anti-oxidant agent)
      with cilostazol (a platelet aggregation inhibitor) would increase the inhibitory
      effect of statins (a lipid-lowering agent) on atherosclerosis in moderately
      hypercholesterolemic rabbits. METHODS AND RESULTS: Thirty Japanese white rabbits
      were fed with a high cholesterol diet for 12 weeks, which was supplemented with
      either 0.005% atorvastatin alone or 0.005% atorvastatin plus 0.3% probucol and
      0.3% cilostazol. Except for high-density lipoprotein cholesterol, no difference
      was found in plasma lipids among vehicle, statin, and the combined treatment
      group. However, atherosclerotic lesions were significantly reduced by statin
      treatment compared with vehicle. Moreover, we found that the anti-atherogenic
      effect of statin was further enhanced by the combined treatment, which was due to
      increased anti-inflammatory and anti-oxidant properties. CONCLUSIONS: These data
      demonstrated that combined drug treatment exhibits potent athero-protective
      effects via pleiotropic functions, such as anti-inflammatory and anti-oxidative
      stress, which is independent of the lipid-lowering effect.

PMID- 26220197
TI  - Intramolecular Redox-Mannich Reactions: Facile Access to the
      Tetrahydroprotoberberine Core.
AB  - Cyclic amines such as pyrrolidine undergo redox-annulations with 2-formylaryl
      malonates. Concurrent oxidative amine alpha-C?H bond functionalization and
      reductive N-alkylation render this transformation redox-neutral. This redox
      Mannich process provides regioisomers of classic Reinhoudt reaction products as
      an entry to the tetrahydroprotoberberine core, enabling the synthesis of (+/-)
      thalictricavine and its epimer. An unusually mild amine-promoted
      dealkoxycarbonylation was discovered in the course of these studies. 

PMID- 26220198
TI  - Evaluation of Lean Body Weight Equation by Dual-Energy X-Ray Absorptiometry
      Measures.
AB  - BACKGROUND: When managing patients with disorders that require clinical
      intervention, a practical assessment of body habitus is valued. The Duffull-Green
      lean body weight (LBW) equation was derived and validated in adults across a wide
      body mass index (BMI) range. Whether this predictive equation will perform well
      in patients at BMI extremes or perform better than a widely used empiric "ideal"
      body weight (IBW) equation is unknown. MATERIALS AND METHODS: Calculated LBW and
      calculated IBW were each compared with the dual-energy x-ray absorptiometry (DXA)
      derived lean body mass (LBM) by simple linear regression. A mixed model was used
      to determine how well the LBW equation performed over time in patients with more
      than 1 DXA measurement. RESULTS: At time 0, 32 patients were 18-67 years old, and
      all were obese (BMI: 36-65 kg/m2), while the remaining 7 had parenteral nutrition
      dependent intestinal failure (BMI: 17-25 kg/m2). A subset of patients underwent
      bariatric surgery after time 0 (BMI at follow-up: 22-49 kg/m2). The LBW equation
      was a predictor of LBM ( R2 = 0.67, P < .0001), while the IBW equation was not (
      R2 = 0.04, P = .25). The LBW equation remained a predictor of LBM over time ( P <
      .0001) without significant interaction by number of months since time 0.
      CONCLUSION: The Duffull-Green LBW equation successfully predicted lean body mass
      in a patient population with a wide range of BMIs at both a single point in time
      and after considerable weight loss. In the clinical setting, an equation that
      performs well in various disease states and body sizes is advantageous.

PMID- 26220199
TI  - Glucagon-Like Peptide-2 Alters Bile Acid Metabolism in Parenteral Nutrition-
      Associated Liver Disease.
AB  - BACKGROUND: We aim to study the mechanisms underlying our previous finding that
      exogenous glucagon-like peptide-2 (GLP-2) treatment in a preclinical model of
      neonatal parenteral nutrition-associated liver disease (PNALD) improves
      cholestasis. METHODS: Neonatal piglets received 17 days of parenteral nutrition
      (PN) therapy and either saline control (PN/Saline n = 8) or GLP-2 treatment at 11
      nmol/kg/d (PN/GLP-2, n = 7). At terminal laparotomy, bile and liver samples were
      collected. The relative gene expression of enzymes involved in bile acid
      synthesis, regulation, and transport was measured in liver by reverse
      transcriptase quantitative polymerase chain reaction. Bile acid composition in
      bile was determined using tandem mass spectrometry. Data were analyzed using 1
      way analysis of variance (ANOVA) or Kruskal-Wallis ANOVA. RESULTS: GLP-2
      increased the expression of bile acid export genes: multidrug resistance
      associated proteins 2 (MRP2) (P = .002) and 3 (MRP3) (P = .037) over saline
      control. GLP-2 increased expression of Farnesoid X receptor (FXR) (P < .001) and
      CYP7A1 (cytochrome P450, family 7, subfamily A, polypeptide 1) (P = .03). GLP-2
      treatment was associated with decreased concentrations of taurohyocholic acid and
      conjugates of toxic lithocholic acid (P < .01). GLP-2 treatment increased the
      liver bile acid content. CONCLUSIONS: GLP-2 treatment was associated with
      alterations in the hepatic expression of genes involved in bile acid metabolism.
      The transcriptomic results indicate the mechanisms at the transcriptional level
      acting to regulate bile acid synthesis and increase bile acid export. Differences
      in bile acid profiles further support a beneficial role for GLP-2 therapy in
      PNALD.

PMID- 26220200
TI  - Intravenous omega-3 Fatty Acids Plus Gemcitabine.
AB  - BACKGROUND: Marine-derived omega-3 fatty acids (omega-3FAs) have proven antitumor
      activity in vivo and in vitro and improve quality of life (QOL) in clinical
      cancer studies. These changes may be mediated by reduction in circulating
      proangiogenic and proinflammatory factors. In this first study of intravenous
      omega-3FAs as a therapy in cancer patients, we aimed to assess if it could
      augment the antitumor activity of gemcitabine in patients with advanced
      pancreatic cancer and improve QOL. MATERIALS AND METHODS: Patients were
      administered gemcitabine 1000 mg/m3 weekly followed by up to 100 g (200 mg/mL) of
      omega-3 rich lipid emulsion for 3 weeks followed by a rest week. This was
      continued for up to 6 cycles, progression, unacceptable toxicity, patient
      request, or death. The primary outcome measure was objective response rate, with
      secondary outcome measures of overall and progression free survival, QOL scores,
      and adverse events. RESULTS: Fifty patients were recruited. Response rate was
      14.3% and disease control rate was 85.7%. Overall and progression free survival
      were 5.9 and 4.8 months, respectively. Increase in global health of > 10% over
      baseline was seen in 47.2% of patients. More than 50% of patients had > 10%
      increase in QOL scores in generic symptom scores and both disease-specific
      domains. Grade 3/4 adverse events were thrombocytopenia (8%), neutropenia (12%),
      nausea or vomiting (4%), and chills (6%). CONCLUSION: Intravenous omega-3FAs in
      combination with gemcitabine shows evidence of improved activity and benefit to
      QOL in patients with advanced pancreas cancer and is worthy of investigation in a
      randomized phase III trial.

PMID- 26220201
TI  - A systematic review and critical appraisal of qualitative metasynthetic practice
      in public health to develop a taxonomy of operations of reciprocal translation.
AB  - INTRODUCTION: Reciprocal translation, the understanding of one study's findings
      in terms of another's, is the foundation of most qualitative metasynthetic
      methods. In light of the proliferation of metasynthesis methods, the current
      review sought to create a taxonomy of operations of reciprocal translation using
      recently published qualitative metasyntheses. METHODS: On 19 August 2013,
      MEDLINE, Embase and PsycINFO were searched. Included articles were full reports
      of metasyntheses of qualitative studies published in 2012 in English-language
      peer-reviewed journals. Two reviewers, working independently, screened records,
      assessed full texts for inclusion and extracted data on methods from each
      included metasynthesis. Systematic review methods used were summarised, and
      metasynthetic methods were inductively analysed to develop the taxonomy. RESULTS:
      Of 61 included metasyntheses, 21 (34%) reported fully replicable search
      strategies and 51 (84%) critically appraised included studies. Based on methods
      in these metasyntheses, we developed a taxonomy of reciprocal translation with
      four overlapping categories: visual representation; key paper integration; data
      reduction and thematic extraction; and line-by-line coding. DISCUSSION: This
      systematic review presents an update on methods and reporting currently used in
      qualitative metasynthesis. It also goes beyond the proliferation of approaches to
      offer a parsimonious approach to understanding how reciprocal translations are
      accomplished across metasynthetis methods.

PMID- 26220202
TI  - The Real Role of N-Heterocyclic Carbene in Reductive Functionalization of CO2: An
      Alternative Understanding from Density Functional Theory Study.
AB  - The mechanisms of reductive functionalization of CO2 to formamide catalyzed by N
      heterocyclic carbene (NHC) were comprehensively studied with DFT calculations.
      New activation mode with much lower energy barrier than those proposed before was
      discovered. In this reaction, NHC acts as neither a CO2 nor a silane activator,
      but as a precursor of the real catalyst, i.e., the in situ formed ionic liquid
      [NHCH](+)[Carbamate](-). In this loose contact ion pair, the negatively charged O
      atom of the carbamate anion becomes the new active site and is free to do
      nucleophilic attack. When amine is absent, CO2 will be converted into methanol.
      In this case, the NHC-CO2 adduct is the real catalytic species, the active site
      shifted from the carbene C atom to the negatively charged O atom. These new
      activation modes follow a pattern of "S(N)2@Si-Acceptor", in which the Si-H bond
      is activated via concerted backside S(N)2 nucleophilic attack by the negatively
      charged O atom, and the leaving hydride is directly accepted by a free CO2
      molecule. The advantages of these new activation modes originate from the
      following points: (1) The ionic liquid [NHCH](+)[Carbamate](-) and NHC-CO2 adduct
      are thermodynamically more stable than NHC. (2) The active site of the NHC
      catalyst is extended outside a lot. Consequently, the large steric effect between
      the NHC arms and the substrates in transition state can be avoided to some
      extent. (3) The O atom has good silicon affinity. In addition, a free CO2
      molecule, whose carbon atom is more electrophilic than those of the CO2 moieties
      in NHC-CO2 adduct and carbamate, acts as an efficient hydride acceptor.

PMID- 26220203
TI  - The role of "cell therapy" in osteonecrosis of the femoral head. A systematic
      review of the literature and meta-analysis of 7 studies.
AB  - BACKGROUND AND PURPOSE: The value of core decrompression for treatment of
      osteonecrosis of the femoral head (ONFH) is unclear. We investigated by a
      literature review whether implantation of autologous bone marrow aspirate,
      containing high concentrations of pluripotent mesenchymal stem cells, into the
      core decompression track would improve the clinical and radiological results
      compared with the classical method of core decompression alone. The primary
      outcomes of interest were structural failure (collapse) of the femoral head and
      conversion to total hip replacement (THR). PATIENTS AND METHODS: All randomized
      and non-randomized control trials comparing simple core decompression with
      autologous bone marrow cell implantation into the femoral head for the treatment
      of ONFH were considered eligible for inclusion. The methodological quality of the
      studies included was assessed independently by 2 reviewers using the Cochrane
      Collaboration tool for assessing risk of bias in randomized studies. Of 496
      relevant citations identified, 7 studies formed the basis of this review.
      RESULTS: The pooled estimate of effect size for structural failure of the femoral
      head favored the cell therapy group, as, in this treatment group, the odds of
      progression of the femoral head to the collapse stage were reduced by a factor of
      5 compared to the CD group (odds ratio (OR) = 0.2, 95% CI: 0.08-0.6; p = 0.02).
      The respective summarized estimate of effect size yielded halved odds for
      conversion to THR in the cell therapy group compared to CD group (OR = 0.6, 95%
      CI: 0.3-1.02; p = 0.06). INTERPRETATION: Our findings suggest that implantation
      of autologous mesenchymal stem cells (MSCs) into the core decompression track,
      particularly when employed at early (pre-collapse) stages of ONFH, would improve
      the survivorship of femoral heads and reduce the need for hip arthroplasty.

PMID- 26220204
TI  - Robust self-navigated body MRI using dense coil arrays.
AB  - PURPOSE: To develop a robust motion estimation method for free-breathing body MRI
      using dense coil arrays. METHODS: Self-navigating pulse sequences can measure
      subject motion without using external motion monitoring devices. With dense coil
      arrays, individual coil elements can provide localized motion estimates. An
      averaged motion estimate over all coils is often used for motion compensation.
      However, this motion estimate may not accurately represent the dominant motion
      within the imaging volume. In this work, a coil clustering method is proposed to
      automatically determine the dominant motion for dense coil arrays. The
      feasibility of the proposed method is investigated in free-breathing abdominal
      MRI and cardiac MRI, and compared with manual motion estimate selection for
      respiratory motion estimation and electrocardiography for cardiac motion
      estimation. RESULTS: Automated motion estimation achieved similar respiratory
      motion estimation compared to manual selection (averaged correlation coefficient
      0.989 and 0.988 for abdominal MRI and cardiac MRI, respectively), and accurate
      cardiac triggering compared to electrocardiography (averaged temporal variability
      17.5 ms). CONCLUSION: The proposed method can provide accurate automated motion
      estimation for body MRI using dense coil arrays. It can enable self-navigated
      free-breathing abdominal and cardiac MRI without the need for external motion
      monitoring devices. Magn Reson Med 76:197-205, 2016. (c) 2015 Wiley Periodicals,
      Inc.

PMID- 26220205
TI  - Response Surface Optimization of Process Parameters and Fuzzy Analysis of Sensory
      Data of High Pressure-Temperature Treated Pineapple Puree.
AB  - The high-pressure processing conditions were optimized for pineapple puree within
      the domain of 400-600 MPa, 40-60  degrees C, and 10-20 min using the response
      surface methodology (RSM). The target was to maximize the inactivation of
      polyphenoloxidase (PPO) along with a minimal loss in beneficial bromelain (BRM)
      activity, ascorbic acid (AA) content, antioxidant capacity, and color in the
      sample. The optimum condition was 600 MPa, 50  degrees C, and 13 min, having the
      highest desirability of 0.604, which resulted in 44% PPO and 47% BRM activities.
      However, 93% antioxidant activity and 85% AA were retained in optimized sample
      with a total color change (?E*) value less than 2.5. A 10-fold reduction in PPO
      activity was obtained at 600 MPa/70  degrees C/20 min; however, the thermal
      degradation of nutrients was severe at this condition. Fuzzy mathematical
      approach confirmed that sensory acceptance of the optimized sample was close to
      the fresh sample; whereas, the thermally pasteurized sample (treated at 0.1 MPa,
      95  degrees C for 12 min) had the least sensory score as compared to others. 

PMID- 26220206
TI  - mTORC1 sustains vision in retinitis pigmentosa.

PMID- 26220207
TI  - Specificity and diversity of the mouse Peyer's patch mononuclear phagocyte
      system.

PMID- 26220209
TI  - Modified multiscale sample entropy computation of laser speckle contrast images
      and comparison with the original multiscale entropy algorithm.
AB  - Laser speckle contrast imaging (LSCI) enables a noninvasive monitoring of
      microvascular perfusion. Some studies have proposed to extract information from
      LSCI data through their multiscale entropy (MSE). However, for reaching a large
      range of scales, the original MSE algorithm may require long recordings for
      reliability. Recently, a novel approach to compute MSE with shorter data sets has
      been proposed: the short-time MSE (sMSE). Our goal is to apply, for the first
      time, the sMSE algorithm in LSCI data and to compare results with those given by
      the original MSE. Moreover, we apply the original MSE algorithm on data of
      different lengths and compare results with those given by longer recordings. For
      this purpose, synthetic signals and 192 LSCI regions of interest (ROIs) of
      different sizes are processed. Our results show that the sMSE algorithm is valid
      to compute the MSE of LSCI data. Moreover, with time series shorter than those
      initially proposed, the sMSE and original MSE algorithms give results with no
      statistical difference from those of the original MSE algorithm with longer data
      sets. The minimal acceptable length depends on the ROI size. Comparisons of MSE
      from healthy and pathological subjects can be performed with shorter data sets
      than those proposed until now.

PMID- 26220208
TI  - p53 amplifies Toll-like receptor 5 response in human primary and cancer cells
      through interaction with multiple signal transduction pathways.
AB  - The p53 tumor suppressor regulates transcription of genes associated with diverse
      cellular functions including apoptosis, growth arrest, DNA repair and
      differentiation. Recently, we established that p53 can modulate expression of
      Toll-like receptor (TLR) innate immunity genes but the degree of cross-talk
      between p53 and TLR pathways remained unclear. Here, using gene expression
      profiling we characterize the global effect of p53 on the TLR5-mediated
      transcription in MCF7 cells. We found that combined activation of p53 and TLR5
      pathways synergistically increases expression of over 200 genes, mostly
      associated with immunity and inflammation. The synergy was observed in several
      human cancer cells and primary lymphocytes. The p53-dependent amplification of
      transcriptional response to TLR5 activation required expression of NFkappaB
      subunit p65 and was mediated by several molecular mechanisms including increased
      phosphorylation of p38 MAP kinase, PI3K and STAT3 signaling. Additionally, p53
      induction increased cytokine expression in response to TNFalpha, another
      activator of NFkappaB and MAP kinase pathways, suggesting a broad interaction
      between p53 and these signaling pathways. The expression of many synergistically
      induced genes is elevated in breast cancer patients responsive to chemotherapy.
      We suggest that p53's capacity to enhance immune response could be exploited to
      increase antitumor immunity and to improve cancer treatment. 

PMID- 26220210
TI  - Hyperspectral wide gap second derivative analysis for in vivo detection of
      cervical intraepithelial neoplasia.
AB  - Hyperspectral reflectance imaging technique has been used for in vivo detection
      of cervical intraepithelial neoplasia. However, the clinical outcome of this
      technique is suboptimal owing to multiple limitations such as nonuniform
      illumination, high-cost and bulky setup, and time-consuming data acquisition and
      processing. To overcome these limitations, we acquired the hyperspectral data
      cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap
      second derivative analysis method. This method effectively reduced the image
      artifacts caused by nonuniform illumination and background absorption.
      Furthermore, with second derivative analysis, only three specific wavelengths
      (620, 696, and 772 nm) are needed for tissue classification with optimal
      separability. Clinical feasibility of the proposed image analysis and
      classification method was tested in a clinical trial where cervical hyperspectral
      images from three patients were used for classification analysis. Our proposed
      method successfully classified the cervix tissue into three categories of normal,
      inflammation and high-grade lesion. These classification results were coincident
      with those by an experienced gynecology oncologist after applying acetic acid.
      Our preliminary clinical study has demonstrated the technical feasibility for in
      vivo and noninvasive detection of cervical neoplasia without acetic acid. Further
      clinical research is needed in order to establish a large-scale diagnostic
      database and optimize the tissue classification technique.

PMID- 26220211
TI  - Mechanically switchable solid inhomogeneous phantom for performance tests in
      diffuse imaging and spectroscopy.
AB  - A mechanically switchable solid inhomogeneous phantom simulating localized
      absorption changes was developed and characterized. The homogeneous host phantom
      was made of epoxy resin with black toner and titanium dioxide particles added as
      absorbing and scattering components, respectively. A cylindrical rod, movable
      along a hole in the block and made of the same material, has a black polyvinyl
      chloride cylinder embedded in its center. By varying the volume and position of
      the black inclusion, absorption perturbations can be generated over a large range
      of magnitudes. The phantom has been characterized by various time-domain diffuse
      optics instruments in terms of absorption and scattering spectra, transmittance
      images, and reflectance contrast. Addressing a major application of the phantom
      for performance characterization for functional near-infrared spectroscopy of the
      brain, the contrast was measured in reflectance mode while black cylinders of
      volumes from ~20  mm3 to ~270  mm3 were moved in lateral and depth directions,
      respectively. The new type of solid inhomogeneous phantom is expected to become a
      useful tool for routine quality check of clinical instruments or implementation
      of industrial standards provided an experimental characterization of the phantom
      is performed in advance.

PMID- 26220212
TI  - Annual air pollution caused by the Hungry Ghost Festival.
AB  - Burning of joss paper and incense is still a very common traditional custom in
      countries with a majority Chinese population. The Hungry Ghost Festival which is
      celebrated in the 7 month of the Chinese calendar is one of the events where joss
      paper and incense are burned as offerings. This study investigates the impact of
      the Ghost Month Festival (open burning event) on air quality by analysis of the
      chemical composition of particulate matter (PM) and rainwater samples collected
      during this event, compared with data collected throughout the year, as well as
      bottom ash samples from burning the original joss paper and incense. The results
      showed that the change in the chemical composition of the rainwater and PM2.5 (PM
      <= 2.5 MUm) atmospheric samples could be correlated directly with burning events
      during this festival, with many elements increasing between 18% and 60% during
      August and September compared to the yearly mean concentrations. The order of
      percentage increase in elemental composition (in rain water and PM2.5) during the
      Hungry Ghost Festival is as follows: Zn > Ca > K > Mg > Fe > Al > Na ~ Mn ~ Ti ~
      V > Cu > As > Ni > Co > Cd > Cr > Pb. The chemical composition of the original
      source materials (joss paper and incense for combustion) and their associated
      bottom ash were analysed to explain the impact of burning on air quality. 

PMID- 26220213
TI  - Effect of short-term heat acclimation with permissive dehydration on
      thermoregulation and temperate exercise performance.
AB  - We examined the effect of short-term heat acclimation with permissive dehydration
      (STHADe) on heat acclimation (HA) and cycling performance in a temperate
      environment. Ten trained male cyclists [mean (SD) maximal oxygen uptake:
      63.3(4.0) mL/kg/min; peak power output (PPO): 385(40) W; training: 10 (3) h/week]
      underwent a STHADe program consisting of 5 days of exercise (maximum 90 min/day)
      in a hot environment (40  degrees C, 50% RH) to elicit isothermic heat strain
      [rectal temperature 38.64(0.27)  degrees C]. Participants abstained from fluids
      during, and 30 min after, HA sessions. Pre- and post-STHADe HA was evaluated
      during euhydrated fixed-intensity exercise (60 min) in hot conditions; the effect
      of STHADe on thermoregulation was also examined under temperate conditions (20
      min fixed-intensity exercise; 22  degrees C, 60% RH). Temperate cycling
      performance was assessed by a graded exercise test (GXT) and 20-km time trial
      (TT). STHADe reduced thermal and cardiovascular strain in hot and temperate
      environments. Lactate threshold [Delta = 16 (17) W] and GXT PPO [Delta = 6 (7) W]
      were improved following STHADe (P < 0.05), but TT performance was not affected (P
      > 0.05), although there was a trend for a higher mean power (P = 0.06). In
      conclusion, STHADE can reduce thermal and cardiovascular strain under hot and
      temperate conditions and there is some evidence of ergogenic potential for
      temperate exercise, but longer HA regimens may be necessary for this to
      meaningfully influence performance. 

PMID- 26220214
TI  - Extra-medullary gastric and hepatic relapse of acute lymphoblastic leukaemia in
      an adolescent: An unusual presentation.

PMID- 26220215
TI  - A combined crossed molecular beam and theoretical investigation of the reaction
      of the meta-tolyl radical with vinylacetylene--toward the formation of
      methylnaphthalenes.
AB  - Crossed molecular beam experiments and electronic structure calculations on the
      reaction of the meta-tolyl radical with vinylacetylene were conducted to probe
      the formation of methyl-substituted naphthalene isomers. We present the
      compelling evidence that under single collision conditions 1- and 2
      methylnaphthalene can be formed without an entrance barrier via indirect
      scattering dynamics through a bimolecular collision of two non-PAH reactants: the
      meta-tolyl radical and vinylacetylene. The electronic structure calculations,
      conducted at the UCCSD(T)-F12b/cc-pVDZ//UM06-2x/cc-pVTZ + ZPE(UM06-2x/cc-pVTZ)
      level of theory, reveal that this reaction is initiated by the barrierless
      addition of the meta-tolyl radical to the terminal vinyl carbon (C1) of
      vinylacetylene, via a van-der-Waals complex implying that this mechanism can play
      a key role in forming methyl-substituted PAHs in low temperature extreme
      environments such as the low temperature interstellar medium and hydrocarbon-rich
      atmospheres of planets and their moons in the outer solar system. The reaction
      mechanism, proposed from the C11H11 potential energy surface, involves a sequence
      of isomerizations involving hydrogen transfer and ring closure, followed by
      hydrogen dissociation, which eventually leads to 1- and 2-methylnaphthalene in an
      overall exoergic process. 

PMID- 26220216
TI  - Chronic obstructive pulmonary disease induced by exposure to biomass smoke is
      associated with a Th2 cytokine production profile.
AB  - Smoking and exposure to biomass smoke induce the release of pro-inflammatory
      mediators and the activation of T helper cells. The resulting inflammatory
      response contributes to the development of COPD. Clinical heterogeneity exists
      among COPD patients, particularly between patients with disease associated with
      tobacco smoking (TS-COPD) and those exposed to biomass smoke (BE-COPD). The aim
      of this study was to identify whether exposure to tobacco and biomass smokes
      promotes different Th responses that contribute to clinical variability. The
      study only included women. The frequency of Th17 cells in patients with TS-COPD
      was significantly higher than in patients with BE-COPD and healthy controls (HC).
      In contrast, patients with BE-COPD had higher levels of Th2 cells than TS-COPD
      and HC. In accordance, IL-4 serum concentration was higher in BE-COPD than in TS
      COPD. Our data indicates that the different responses induced by these two
      irritants may underlie the clinical heterogeneity between TS- and BE-COPD
      patients. 

PMID- 26220217
TI  - Target Inhibition of IL-1 Receptor Prevents Ifosfamide Induced Hemorrhagic
      Cystitis in Mice.
AB  - PURPOSE: Hemorrhagic cystitis is an important dose limiting side effect of
      ifosfamide based cancer chemotherapy. Despite chemoprophylaxis inflammation can
      still be found in cystoscopy guided biopsies. Previous studies confirmed the role
      of TNF-alpha and IL-1beta. We evaluated the protective effect of the IL-1R
      antagonist anakinra and the anti-TNF-alpha antibody infliximab in experimental
      ifosfamide induced hemorrhagic cystitis. MATERIALS AND METHODS: Hemorrhagic
      cystitis was induced by an injection of ifosfamide (400 mg/kg intraperitoneally)
      in Swiss wild-type C57Bl/6, IL-1R-/-, TNFR1-/- or TNFR1/R2-/- mice. Mice were
      treated 30 minutes before ifosfamide with anakinra (100 mg/kg intraperitoneally),
      infliximab (5 mg/kg intraperitoneally) or vehicle. Visceral nociception was
      evaluated after hemorrhagic cystitis induction. At 12 hours the animals were
      sacrificed. Bladders were harvested to assess bladder wet weight, vascular
      permeability, macroscopic and microscopic findings, muscle contractility, and for
      cystometrography. Inflammatory cell infiltration was assessed by myeloperoxidase
      assay and flow cytometry. RESULTS: Anakinra attenuated hemorrhage, edema,
      neutrophil infiltration, visceral hyperalgesia and bladder dysfunction. IL-1R-/-
      mice also showed milder hemorrhagic cystitis. Infliximab inhibited bladder edema
      and visceral hyperalgesia without preventing hemorrhage, bladder dysfunction,
      neutrophils or accumulation. Additionally, the lack of TNFR1 decreased bladder
      edema but not cell infiltration whereas concomitant deficiency of TNFR1 and TNFR2
      resulted in worse hemorrhagic cystitis. CONCLUSIONS: Anakinra is effective for
      preventing experimentally ifosfamide induced hemorrhagic cystitis. It seems that
      neutrophil and macrophage infiltration in this circumstance depends on IL-1
      signaling through IL1R. Possibly TNFR2 has a protective role in hemorrhagic
      cystitis.

PMID- 26220218
TI  - The Effects of Local and Systemic Growth Hormone Treatment on Germ Cell
      Population and Fertility in an Experimental Unilateral Testicular Torsion and
      Orchiectomy Model.
AB  - PURPOSE: We evaluated the effects of local and systemic growth hormone on the
      germ cell population of the contralateral testes of pubertal rats subjected to
      unilateral testicular torsion and orchiectomy 24 hours later. MATERIALS AND
      METHODS: A total of 40 male Wistar-Albino rats at age 3 weeks were divided into 5
      groups. In the sham operated group the right testis was sutured and orchiectomy
      was performed 24 hours later. In groups 2 to 5 orchiectomy was performed 24 hours
      later following testicular torsion. In groups 3 and 4 unloaded and growth hormone
      loaded gelatin films, respectively, were sutured on the contralateral testes. In
      group 5 systemic growth hormone was administered for 7 days. Five weeks later
      each rat was cohabited with 2 female rats and the left testes were removed for
      evaluation. Mean seminiferous tubular diameter, mean testicular biopsy score and
      the mean haploid cell percentage were calculated. Mating studies were performed
      and fertility parameters were assayed. RESULTS: Mean seminiferous tubular
      diameter, mean testicular biopsy score and the mean haploid cell percentage of
      the contralateral testes were significantly decreased in the control and gelatin
      groups compared with the other groups. There was no difference between the local
      and systemic growth hormone groups regarding the haploid cell percentage. There
      were no differences between the groups in mean fetus numbers, mating or fertility
      and fecundity indexes except in the gelatin group, in which the mean fetus number
      was significantly lower. CONCLUSIONS: Fertility is not affected in rats after 24
      hours of testicular torsion and orchiectomy, although there is germ cell injury
      and a decrease in the percent of haploid cells. Growth hormone administration
      resulted in the restoration of germ cell histology and an increase in the haploid
      cell percentage of the contralateral testes. Growth hormone may improve fertility
      after unilateral testicular torsion and orchiectomy.

PMID- 26220219
TI  - Effects of perceptual and semantic cues on ERP modulations associated with
      prospective memory.
AB  - Prospective memory involves the formation and execution of intended actions and
      is essential for autonomous living. In this study (N=32), the effect of the
      nature of PM cues (semantic versus perceptual) on established event-related
      potentials (ERPs) elicited in PM tasks (N300 and prospective positivity) was
      investigated. PM cues defined by their perceptual features clearly elicited the
      N300 and prospective positivity whereas PM cues defined by semantic relatedness
      elicited prospective positivity. This calls into question the view that the N300
      is a marker of general processes underlying detection of PM cues, but supports
      existing research showing that prospective positivity represents general post
      retrieval processes that follow detection of PM cues. Continued refinement of ERP
      paradigms for understanding the neural correlates of PM is needed. 

PMID- 26220220
TI  - Aortic rupture after thoracic endovascular repair in a patient with Familial
      Thoracic Aortic Aneurysm and Dissections type 6 (FTAAD6).

PMID- 26220221
TI  - Risk factors of venous thromboembolism in focal segmental glomerulosclerosis with
      nephrotic syndrome.
AB  - BACKGROUND: Venous thromboembolism (VTE) is an important and potentially life
      threatening complication in focal segmental glomerulosclerosis (FSGS). The aim of
      this study was to investigate the prevalence and predisposing risk factors of
      venous thromboembolism in patients with FSGS with nephrotic syndrome. METHODS: A
      total of 120 FSGS patients with nephrotic syndrome were enrolled in this study.
      Venous thromboembolism was confirmed by contrast-enhanced dual-source computed
      tomography angiography or magnetic resonance venography. Potential clinical and
      laboratory risk factors for VTE were screened. RESULTS: Venous thrombosis was
      demonstrated in 12 (10 %) patients. Venous thrombosis occurred during the first
      episode of nephrotic syndrome in 3 patients and during a relapse in 9 patients.
      Eight patients had a pulmonary embolism, four had a renal vein thrombosis, three
      had a lower limb deep vein thrombosis, one had a cerebral sinovenous thrombosis,
      and one had a portal vein thrombosis. The positive predictive value for the D
      dimer level was 22.4 % in the patients with FSGS, and the negative predictive
      value for the D-dimer level was 100 %. Of the screened risk factors, higher
      hematocrit and relapse of nephrotic syndrome were risk factors for VTE. Other
      risk factors, such as proteinuria, hypoalbuminemia, platelet count, fibrinogen
      level, and antithrombin III level, were not risk factors for VTE in patients with
      FSGS. CONCLUSION: We found that the prevalence of venous thromboembolism is
      approximately 10 % in FSGS patients with nephrotic syndrome. Most of the patients
      had a PE. Hemoconcentration and relapse of nephrotic syndrome were risk factors
      for the development of VTE in FSGS. Negative D-dimer may exclude venous
      thromboembolism in patients with nephrotic syndrome.

PMID- 26220222
TI  - Family-based analysis of eight susceptibility loci in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that is proposed
      to have a genetic basis. A recent genome-wide association study (GWAS) identified
      eight new risk loci that are independently associated with PCOS. To further
      validate the findings, a total of 321 case-parent trios (963 participants) who
      had a proband affected with PCOS were recruited for the family-based study. The
      transmission disequilibrium test (TDT) was used to analyze associations between
      PCOS and ten single nucleotide polymorphisms (SNPs) mapped to eight new
      susceptibility loci. Significant differences in transmission were observed for
      the SNPs rs2349415 (located in the FSHR gene, P = 0.0001) and rs3802457 (located
      in the C9orf3 gene, P = 0.0001), even after correction for multiple testing bias.
      The present data provides further evidence for an association between two
      susceptibility loci, 2p16.3 and 9q22.32, and PCOS. Follow-up functional studies
      on the FSHR and C9orf3 genes are required to understand their roles in PCOS
      development. 

PMID- 26220225
TI  - Adolescent dietary patterns are associated with lifestyle and family psycho
      social factors - CORRIGENDUM.

PMID- 26220224
TI  - Multiple loci not only Rf3 involved in the restoration ability of pollen
      fertility, anther exsertion and pollen shedding to S type cytoplasmic male
      sterile in maize.
AB  - KEY MESSAGE: Thirty loci for fertility restoration of pollen fertility, anther
      exsertion and pollen shedding to maize CMS-S were identified by GWAS. S type
      cytoplasmic male sterile (CMS-S) is the main type of CMS in maize; poor
      understanding of the genetic architecture of fertility restoration to CMS-S is
      one of the reasons to impede its utility in hybrid breeding. In this study,
      genome-wide identification of genetic loci for fertility restoration ability to
      CMS-S was firstly conducted with a set of testcrossing association mapping panel
      in three environments. A total of 19, 3 and 8 significant loci (P < 1.8 * 10(-6),
      alpha = 1) for pollen fertility, anther exsertion and pollen shedding were
      identified, respectively, and individual locus explained up to 28.26% of
      phenotypic variation. Of them, only Rf3, the main restorer-fertility gene of CMS
      S, was identified for the three traits simultaneously. In addition, 83 candidate
      genes within the 100 kb extension regions of these loci were predicted. These
      results revealed that besides Rf3 multiple genetic loci and mechanisms are
      involved in the fertility restoration ability to CMS-S. Results in this study
      would provide important information for understanding the genetic architecture of
      fertility restoration to CMS-S in maize.

PMID- 26220223
TI  - High-density mapping of the major FHB resistance gene Fhb7 derived from
      Thinopyrum ponticum and its pyramiding with Fhb1 by marker-assisted selection.
AB  - KEY MESSAGE: Wheat lines with shortened Th. ponticum chromatin carrying Fhb7 and
      molecular markers linked to Fhb7 will accelerate the transfer of Fhb7 to breeding
      lines and provide an important resource for future map-based cloning of this
      gene. Fusarium head blight is a major wheat disease globally. A major FHB
      resistance gene, designated as Fhb7, derived from Thinopyrum ponticum, was
      earlier transferred to common wheat, but was not used in wheat breeding due to
      linkage drag. The aims of this study were to (1) saturate this FHB resistance
      gene region; (2) develop and characterize secondary translocation lines with
      shortened Thinopyrum segments carrying Fhb7 using ph1b; (3) pyramid Fhb7 and Fhb1
      by marker-assisted selection. Fhb7 was mapped in a 1.7 cM interval that was
      flanked by molecular markers XsdauK66 and Xcfa2240 with SSR, diversity arrays
      technology, EST-derived and conserved markers. KS24-2 carrying Fhb7 was analyzed
      with molecular markers and genomic in situ hybridization, confirming it was a
      7DS.7el2L Robertsonian translocation. To reduce the Thinopyrum chromatin segments
      carrying Fhb7, a BC1F2 population (Chinese Spring ph1bph1b*2/KS24-2) was
      developed and genotyped with the markers linked to Fhb7. Two new translocation
      lines (SDAU1881 and SDAU1886) carrying Fhb7 on shortened alien segments
      (approximately 16.1 and 17.3% of the translocation chromosome, respectively) were
      developed. Furthermore, four wheat lines (SDAU1902, SDAU1903, SDAU1904, and
      SDAU1906) with the pyramided markers flanking Fhb1 and Fhb7 were developed and
      the FHB responses indicated lines with mean NDS ranging from 1.3 to 1.6 had
      successfully combined Fhb7 and Fhb1. Three new molecular markers associated with
      Fhb7 were identified and validated in 35 common wheat varieties. The
      translocation lines with shortened alien segments carrying Fhb7 (and Fhb1) and
      the markers closely linked to Fhb7 will be useful for improving wheat scab
      resistance.

PMID- 26220236
TI  - Longitudinal Study of Headache Trajectories in the Year After Mild Traumatic
      Brain Injury: Relation to Posttraumatic Stress Disorder Symptoms.
AB  - OBJECTIVE: To examine headache trajectories among persons with mild traumatic
      brain injury (MTBI) in the year after injury and the relation of headache
      trajectory to posttraumatic stress disorder (PTSD) at 1 year postinjury. DESIGN:
      Prospective, longitudinal study. SETTING: Participants were recruited through a
      university medical center and participated in follow-up assessments by telephone.
      PARTICIPANTS: Prospectively enrolled individuals (N=212) within 1 week of MTBI
      who were hospitalized for observation or other system injuries. Participants were
      assessed at baseline and 3, 6, and 12 months postinjury. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Participants rated average headache pain
      intensity using the 0 to 10 numerical rating scale at each assessment period. The
      PTSD Checklist-Civilian Version was completed at 12 months postinjury. RESULTS:
      Latent class growth analysis produced a 4-trajectory group model, with groups
      labeled resolved, worsening, improving, and chronic. Multivariate regression
      modeling revealed that younger age and premorbid headache correlated with
      membership in the worse trajectory groups (worsening and chronic; P<.001).
      Univariate regression revealed a significant association between PTSD and
      membership in the worse trajectory groups (P<.001). CONCLUSIONS: Headache is
      common in the year after MTBI, with younger people, persons who previously had
      headaches, and persons with PTSD more likely to report chronic or worsening
      headache. Further research is needed to examine whether PTSD symptoms exacerbate
      headaches or whether problematic headache symptoms exacerbate PTSD.

PMID- 26220237
TI  - Improvement of Kidney Function Following Bariatric Surgery: Hope or Illusion?

PMID- 26220238
TI  - Morbidity Rates and Weight Loss After Roux-en-Y Gastric Bypass, Sleeve
      Gastrectomy, and Adjustable Gastric Banding in Patients Older Than 60 Years old:
      Which Procedure to Choose?
AB  - BACKGROUND: As life expectancy increases, more elderly patients fit into the
      criteria for bariatric procedures. The aim of our study is to evaluate and
      compare the safety and efficacy of Roux-en-Y gastric bypass (RYGB), laparoscopic
      sleeve gastrectomy (LSG), and laparoscopic adjustable gastric banding (LAGB) in
      patients older than 60. MATERIAL AND METHODS: Between January 2005 and December
      2013, 68 LAGB, 73 LSG, and 212 RYGB patients were 60 years or older at the time
      of primary procedure. A retrospective review was performed in these patients.
      RESULTS: Mean age and body mass index (BMI) was 62.7 +/- 2.2, 64.1 +/- 2.9, and
      62.6 +/- 2.3 years and 42.7 +/- 5.6, 44.0 +/- 7.0, and 45.2 +/- 6.7 kg/m(2) for
      LAGB, LSG, and RYGB at the time of procedure, respectively. Seven (10.3%)
      patients from the LAGB, 3 (4.1%) from the LSG, and 29 (13.8%) from the RYGB group
      required readmissions. Reoperation rate was 10.3, 1.4, and 9.5% in LAGB, LSG, and
      RYGB, respectively. The difference in reoperation rates was statistically
      significant (p < 0.03) while that in readmission rates was not (p > 0.58).
      Procedure-related mortality rate was 1.4% in the RYGB group, while no mortality
      was observed in LSG and LAGB groups. At 6, 12, and 18 months postoperatively,
      mean percentage of excess weight loss were highest in the RYGB group, followed by
      LSG and LAGB group (p < 0.01). Mean number of comorbidities at the last follow-up
      significantly decreased in LSG and RYGB patients. CONCLUSIONS: LSG showed the
      lowest readmission and reoperation rate, and RYGB patients had the highest
      mortality rate. Weight loss and comorbidity resolution were effectively achieved
      in RYGB and LSG patients.

PMID- 26220240
TI  - Letter to the Editor: Bariatric Surgery Worldwide 2013 Reveals a Rise in Mini
      Gastric Bypass.

PMID- 26220239
TI  - The Effect of Bariatric Surgery Type on Lipid Profile: An Age, Sex, Body Mass
      Index and Excess Weight Loss Matched Study.
AB  - BACKGROUND: Bariatric surgery improves lipid profile. A still unanswered question
      is whether this improvement is merely weight-dependent or also results from
      factors inherent to specificities of the bariatric procedure. We aimed to study
      lipid profile 1 year after bariatric surgery and compare its changes between the
      different procedures in patients matched for initial weight and weight loss.
      METHODS: We retrospectively analysed patients submitted to Roux-en-Y gastric
      bypass (RYGB), adjustable gastric banding (AGB) or sleeve gastrectomy (SG)
      between 2010 and 2013. Patients were matched for age (+/-5 years), sex, pre
      surgery body mass index (BMI) (+/-2 Kg/m(2)) and excess weight loss (EWL) (+/
      5%). Baseline and 1-year lipid profile, its variation and percentage of variation
      was compared between surgeries. RESULTS: We analysed 229 patients: 72 pairs RYGB
      AGB, 47 pairs RYGB-SG and 33 pairs AGB-SG. The median age was 41 (35-52) years
      and 11.8% were male. Pre-operative BMI was 44.0 +/- 4.6 and 32.1 +/- 4.4 Kg/m(2)
      at 1 year. EWL at 1 year was 64.2 +/- 18.9%. There were no differences in
      baseline lipid profile between patients submitted to different types of bariatric
      surgery. At 1 year, high-density lipoprotein cholesterol (HDL) and triglycerides
      (TG) improved similarly with all surgeries. Total cholesterol (TC) and low
      density lipoprotein cholesterol (LDL) at 1 year decreased significantly more in
      patients submitted to RYGB than in weight-matched patients undergoing AGB or SG.
      CONCLUSIONS: RYGB is the only bariatric surgery that reduces TC and LDL in age-,
      sex-, BMI- and EWL-matched patients. All three procedures improved TG and HDL
      similarly when the confounding effect of weight loss is eliminated.

PMID- 26220241
TI  - Predictive Factors for Insufficient Weight Loss After Bariatric Surgery: Does
      Obstructive Sleep Apnea Influence Weight Loss?
AB  - BACKGROUND: Important endpoints of bariatric surgery are weight loss and
      improvement of comorbidities, of which obstructive sleep apnea (OSA) is the
      highest accompanying comorbidity (70%). This study aimed to evaluate the
      influence of OSA on weight loss after bariatric surgery and to provide predictive
      factors for insufficient weight loss (defined as <=50% excess weight loss (EWL))
      at 1 year follow-up. METHODS: All consecutive patients, who underwent primary
      laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy between
      2006 and 2014 were retrospectively reviewed. Patients with data on preoperative
      apnea-hypopnea index (AHI) and pre- and postoperative body mass index (BMI) were
      included. After surgery, the percentage excess weight loss (%EWL) and BMI changes
      were compared between preoperatively diagnosed OSA-, subdivided in mild,
      moderate, and severe OSA, and non-OSA patients. Multivariable logistic regression
      analysis evaluated predictive factors for <=50% EWL. RESULTS: A total of 816
      patients, 522 (64%) with and 294 (36%) without OSA, were included. After 1 year,
      OSA patients achieved less %EWL than non-OSA patients (65.5 SD 20.7 versus 70.3
      SD 21.0; p < 0.01). The lowest %EWL was seen in severe OSA patients (61.7 SD
      20.2). However, when adjusted for waist circumference, BMI, and age, no effect of
      OSA was seen on %EWL or changes in BMI. Although AHI, gender, age, BMI, type of
      surgery, and type II diabetes were predictive factors for <=50% EWL (area under
      the curve 0.778), the AHI as variable was of little importance. CONCLUSIONS: The
      presence of OSA does not individually impair weight loss after bariatric surgery.

PMID- 26220242
TI  - Erratum to: Correlation of Childhood Obesity and Related Insulin Resistance with
      Leptin and Retinol Binding Protein 4.

PMID- 26220243
TI  - Measles Outbreak in High Risk Areas of Delhi: Epidemiological Investigation and
      Laboratory Confirmation.
AB  - OBJECTIVE: To describe epidemiological and laboratory characteristics of the
      measles outbreaks recorded in the urban slums of Delhi (designated as high risk
      areas under the Polio program), from February through July 2014. METHODS: As a
      part of surveillance and containment measures, an extensive field investigation
      for measles case search (WHO definition) through 'house to house survey' was
      conducted by district health teams and field volunteers of National Polio
      Surveillance Project (NPSP), WHO, Delhi from February through July, 2014. The
      data generated by the health teams was collected and analyzed. RESULTS: About 1.1
      million households in the high risk areas of Delhi were surveyed for
      epidemiological investigations. A total of 1337 suspected measles cases were
      reported. The case fatality rate (CFR) was 1.2 %. Statistical analysis showed
      significant relation between age of the child (measles case) and immunization
      status. Higher numbers of reported cases were above 5 y and less than 9 mo of
      age. Measles IgM was detected in 132 cases and D8 strain was isolated on
      genotyping. CONCLUSIONS: The outbreak was predominantly localized to the high
      risk areas (urban slums) of the city. Low CFR was reported during the outbreaks.
      The outbreaks highlight the need to extend the reach of immunization services to
      urban slums and strengthen measles surveillance including laboratory based
      surveillance.

PMID- 26220244
TI  - Newer Diagnostic Tests for Pulmonary Tuberculosis in Children.
AB  - It has been well recognized that the diagnosis of pulmonary tuberculosis in
      children is often compromised by non-specific symptoms, paucibacillary nature of
      the disease, and the difficulty in collecting the specimen. Consequently, most
      tuberculosis cases in children are not confirmed, due to which the estimation of
      the global burden of tuberculosis in children may be inaccurate. There has also
      been a common misperception that diagnosis of tuberculosis and collecting
      respiratory specimen in children is always difficult. Because of this,
      microbiological confirmation of tuberculosis in young children is not routinely
      attempted in most endemic areas. With the emergence of HIV-related tuberculosis
      disease and drug-resistant tuberculosis, the availability of accurate, rapid and
      child friendly diagnostic tools to identify Mycobacterium tuberculosis in
      respiratory specimen are urgently required in endemic settings. There have been a
      large number of studies evaluating new diagnostic tests for tuberculosis in the
      past decade, but few have been evaluated in children. This review will address
      the developments in respiratory specimen collection and laboratory diagnostic
      tests of tuberculosis, with a focus on those that have been evaluated in
      children. 

PMID- 26220245
TI  - Ataxia Telangiectasia Masquerading as Hyper IgM Syndrome.

PMID- 26220246
TI  - Sepsis may not be a risk factor for mortality in patients with acute kidney
      injury treated with continuous renal replacement therapy.
AB  - PURPOSE: We aimed to study the clinical characteristics, courses, and outcomes of
      critically ill patients with septic acute kidney injury (AKI) treated with
      continuous renal replacement therapy (CRRT) in comparison with nonseptic AKI
      treated with CRRT. METHODS: This is a multicenter retrospective observational
      study conducted in 14 Japanese intensive care units in 2010. All adult patients
      with severe AKI treated with CRRT were eligible (n = 343), and information on
      patient characteristics, variables at CRRT initiation, CRRT settings, and
      outcomes was collected. Patients were categorized into the septic AKI group and
      the nonseptic AKI group according to contributing factors to AKI. RESULTS:
      Approximately half of study patients (48.7%) had sepsis/septic shock as a
      contributing factor to AKI, and patients with septic AKI treated with CRRT had
      more serious clinical conditions than patients with nonseptic AKI. However, no
      significant difference was observed in intensive care unit mortality (48.5% vs
      43.8%; P = .44) and hospital mortality (61.1% vs 56.3%; P = .42) between patients
      with septic and nonseptic AKIs treated with CRRT. Furthermore, sepsis was
      associated with lower hospital mortality (odds ratio, 0.378; P = .012) in
      multivariable regression analysis. CONCLUSION: Sepsis may not be a risk factor
      for mortality in patients with AKI whose condition has become severe enough to
      require CRRT.

PMID- 26220247
TI  - 7alpha-Hydroxypregnenolone, a key neuronal modulator of locomotion, stimulates
      upstream migration by means of the dopaminergic system in salmon.
AB  - Salmon migrate upstream against an opposing current in their natal river.
      However, the molecular mechanisms that stimulate upstream migratory behavior are
      poorly understood. Here, we show that 7alpha-hydroxypregnenolone (7alpha-OH
      PREG), a newly identified neuronal modulator of locomotion, acts as a key factor
      for upstream migration in salmon. We first identified 7alpha-OH PREG and
      cytochrome P450 7alpha-hydroxylase (P4507alpha), a steroidogenic enzyme producing
      7alpha-OH PREG, in the salmon brain and then found that 7alpha-OH PREG synthesis
      in the brain increases during upstream migration. Subsequently, we demonstrated
      that 7alpha-OH PREG increases upstream migratory behavior of salmon. We further
      found that 7alpha-OH PREG acts on dopamine neurons in the magnocellular preoptic
      nucleus during upstream migration. Thus, 7alpha-OH PREG stimulates upstream
      migratory behavior through the dopaminergic system in salmon. These findings
      provide new insights into the molecular mechanisms of fish upstream migration. 

PMID- 26220248
TI  - In-solution hybridization for mammalian mitogenome enrichment: pros, cons and
      challenges associated with multiplexing degraded DNA.
AB  - Here, we present a set of RNA-based probes for whole mitochondrial genome in
      solution enrichment, targeting a diversity of mammalian mitogenomes. This probes
      set was designed from seven mammalian orders and tested to determine the utility
      for enriching degraded DNA. We generated 63 mitogenomes representing five orders
      and 22 genera of mammals that yielded varying coverage ranging from 0 to >5400X.
      Based on a threshold of 70% mitogenome recovery and at least 10* average
      coverage, 32 individuals or 51% of samples were considered successful. The
      estimated sequence divergence of samples from the probe sequences used to
      construct the array ranged up to nearly 20%. Sample type was more predictive of
      mitogenome recovery than sample age. The proportion of reads from each individual
      in multiplexed enrichments was highly skewed, with each pool having one sample
      that yielded a majority of the reads. Recovery across each mitochondrial gene
      varied with most samples exhibiting regions with gaps or ambiguous sites. We
      estimated the ability of the probes to capture mitogenomes from a diversity of
      mammalian taxa not included here by performing a clustering analysis of published
      sequences for 100 taxa representing most mammalian orders. Our study demonstrates
      that a general array can be cost and time effective when there is a need to
      screen a modest number of individuals from a variety of taxa. We also address the
      practical concerns for using such a tool, with regard to pooling samples,
      generating high quality mitogenomes and detail a pipeline to remove chimeric
      molecules. 

PMID- 26220250
TI  - In Vitro and In Vivo Performance of a Pre-Filled, Electrochemically-Actuated
      Infusion System.
AB  - PURPOSE: A novel infusion system (PatchPump(r)) has been developed using an
      electrochemical actuator and a semi-flexible container to deliver liquid
      formulations through an infusion set. In vitro studies characterized pump
      performance, and clinical studies evaluated functionality and pharmacokinetic
      (PK) performance in humans. METHODS: Total delivered volume and flow rate
      accuracy were determined in vitro by real-time gravimetric analysis.
      Functionality was evaluated in vivo using prototype devices delivering saline for
      18 h in a clinical study enrolling 10 healthy volunteers. A second clinical study
      examined the PK of delivering treprostinil at an average dose of 2.3 ng/kg/min to
      5 healthy volunteers for 18 h. RESULTS: Relative to a design target of 0.042
      mL/hr, the average flow rate of 23 PatchPumps operating for 48 continuous hours
      was 0.043 +/- 0.007 mL/hr as tested in vitro. In vivo functionality was confirmed
      by complete infusion of saline for the entire duration with only mild and
      transient adverse effects. PK results with an infusion rate of 0.045 mL/hr of
      treprostinil resulted in mean Css of 297 pg/mL and T1/2 of 4.44 h, comparable to
      prior studies using conventional infusion pumps. CONCLUSIONS: The results of
      these studies demonstrate a successful proof-of-concept for the PatchPump
      technology.

PMID- 26220249
TI  - Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility.
AB  - PURPOSE: Compound solubility serves as a surrogate indicator of oral
      biopharmaceutical performance. Between infancy and adulthood, marked
      compositional changes in gastrointestinal (GI) fluids occur. This study serves to
      assess how developmental changes in GI fluid composition affects compound
      solubility. METHODS: Solubility assessments were conducted in vitro using
      biorelevant media reflective of age-specific pediatric cohorts (i.e., neonates
      and infants). Previously published adult media (i.e., FaSSGF, FeSSGF, FaSSIF.v2,
      and FeSSIF.v2) were employed as references for pediatric media development.
      Investigations assessing age-specific changes in GI fluid parameters (i.e.,
      pepsin, bile acids, pH, osmolality, etc.) were collected from the literature and
      served to define the composition of neonatal and infant media. Solubility
      assessments at 37  degrees C were conducted for seven BCS Class II compounds
      within the developed pediatric and reference adult media. RESULTS: For six of the
      seven compounds investigated, solubility fell outside an 80-125% range from adult
      values in at least one of the developed pediatric media. This result indicates a
      potential for age-related alterations in oral drug performance, especially for
      compounds whose absorption is delimited by solubility (i.e., BCS Class II).
      CONCLUSION: Developmental changes in GI fluid composition can result in relevant
      discrepancies in luminal compound solubility between children and adults.

PMID- 26220251
TI  - Polymerase Spiral Reaction (PSR): A novel isothermal nucleic acid amplification
      method.
AB  - In this study, we report a novel isothermal nucleic acid amplification method
      only requires one pair of primers and one enzyme, termed Polymerase Spiral
      Reaction (PSR) with high specificity, efficiency, and rapidity under isothermal
      condition. The recombinant plasmid of blaNDM-1 was imported to Escherichia coli
      BL21, and selected as the microbial target. PSR method employs a Bst DNA
      polymerase and a pair of primers designed targeting the blaNDM-1 gene sequence.
      The forward and reverse Tab primer sequences are reverse to each other at their
      5' end (Nr and N), whereas their 3' end sequences are complementary to their
      respective target nucleic acid sequences. The PSR method was performed at a
      constant temperature 61  degrees C-65  degrees C, yielding a complicated spiral
      structure. PSR assay was monitored continuously in a real-time turbidimeter
      instrument or visually detected with the aid of a fluorescent dye (SYBR Greeni),
      and could be finished within 1 h with a high accumulation of 10(9) copies of the
      target and a fine sensitivity of 6 CFU per reaction. Clinical evaluation was also
      conducted using PSR, showing high specificity of this method. The PSR technique
      provides a convenient and cost-effective alternative for clinical screening, on
      site diagnosis and primary quarantine purposes. 

PMID- 26220252
TI  - The clinicopathological spectrum of trichoepitheliomas: a retrospective
      descriptive study.
AB  - BACKGROUND: Trichoepithelioma (TE) is a benign adnexal neoplasm derived from
      basal cells in the hair follicle. Solitary TE occurs sporadically as opposed to
      the multiple familial variant that presents as an autosomal dominant
      genodermatosis. The solitary variant can be confused with basal cell carcinoma
      both clinically and histologically. Multiple familial TEs are a cosmetically
      disfiguring condition with limited satisfactory treatment options. METHOD: Skin
      biopsies diagnosed as TE from January 1, 2001, to December 31, 2011, were
      retrieved from the archives of the Division of Anatomical Pathology (University
      of Stellenbosch and National Health Laboratory Service, Cape Town, South Africa).
      Clinical and demographic data were retrieved from the patient records at
      Tygerberg Academic Hospital. Data of patients with solitary TE and multiple TE
      were compared. RESULTS: Thirty-three biopsy specimens were collected from 30
      patients. Twenty patients had solitary TE, nine patients had multiple TEs, and
      one patient had multiple linear TEs. Multiple TEs started to develop in patients
      at an average age of 17.3 years. Three patients in the study had tumoral TE with
      a diameter greater than 20 mm. One patient had TE associated with a basal cell
      carcinoma. Multiple TEs were commonly misdiagnosed clinically as tuberous
      sclerosis and showed a cribriform histopathological tumor pattern in 80% of cases
      as compared to only 10% of solitary TEs. CONCLUSION: The current study was
      confined to a cohort of patients, in the Western Cape Province of South Africa,
      whose ethnic and geographic origins were not available. The extrapolation of
      findings from this study to the rest of the South African population may not be
      valid. A cribriform growth pattern occurs in the majority of cases of multiple
      TEs.

PMID- 26220253
TI  - Retromer: Structure, function, and roles in mammalian disease.
AB  - Retrograde transport from the endosome to the Golgi is mediated by a 5 protein
      complex known as the retromer. These five proteins (Vps5, Vps17, Vps26, Vps29,
      and Vps35 in yeast and SNX1/2, SNX5/6, Vps26, Vps29, and Vps35 in mammalian
      cells) act as a coat for vesicles budding off of the endosome, as well as perform
      cargo sorting at the endosome. The retromer is well conserved between yeast and
      mammalian systems, though variations exist within the mammalian retromer.
      Functionally, the retromer has been linked to prominent neurodegenerative
      diseases such as Alzheimer's and Parkinson's in human models as well as diabetes
      mellitus. However, the retromer also plays a role in the virulence of several
      microbial pathogens. Despite the current understanding of the retromer complex,
      there are still many questions to be answered in regards to its overall role in
      cell homeostasis. 

PMID- 26220254
TI  - Sirolimus vs cyclosporine after induction with basiliximab does not promote
      regulatory T cell expansion in de novo kidney transplantation: Results from a
      single-center randomized trial.
AB  - Regulatory T cells (Tregs), defined as CD4+CD25+highFoxP3+CD127- cells, could
      promote tolerance in renal transplantation (Tx). In an open-label, randomized,
      controlled trial 62 de-novo Tx recipients received induction with basiliximab and
      cyclosporine A (CsA) for the first month after Tx and then were assigned to
      treatment with sirolimus (SRL) or CsA and followed up for 2 years. The primary
      endpoint was to evaluate the effects of induction and maintenance treatments on
      circulating Tregs, while the secondary endpoint was the assessment of Treg renal
      infiltration and the relationship between Treg count and clinical outcomes. There
      were no significant differences in either circulating or tissue Treg number
      between the two groups. At 1 month post-Tx, all patients presented a profound
      Treg depletion, followed by a significant increase in Tregs that resulted stable
      during the follow-up. The same trend was also observed for non-activated Tregs
      (CD69-) and for other immunocompetent cells (CD4+ and CD8+ T cells, B cells and
      NK cells). Moreover, the Treg count did not correlate either with renal function
      or with acute rejection and graft loss. Initial immunosuppression is crucial to
      regulate circulating Tregs, regardless of subsequent immunosuppressive
      maintenance regimens. Strategies aiming to promote tolerance should consider the
      effects of different induction regimens.

PMID- 26220255
TI  - IL-12-polarized Th1 cells produce GM-CSF and induce EAE independent of IL-23.
AB  - CD4(+) T-helper (Th) cells reactive against myelin antigens mediate the mouse
      model experimental autoimmune encephalomyelitis (EAE) and have been implicated in
      the pathogenesis of multiple sclerosis (MS). It is currently debated whether
      encephalitogenic Th cells are heterogeneous or arise from a single lineage. In
      the current study, we challenge the dogma that stimulation with the monokine IL
      23 is universally required for the acquisition of pathogenic properties by myelin
      reactive T cells. We show that IL-12-modulated Th1 cells readily produce IFN
      gamma and GM-CSF in the CNS of mice and induce a severe form of EAE via an IL-23
      independent pathway. Th1-mediated EAE is characterized by monocyte-rich CNS
      infiltrates, elicits a strong proinflammatory cytokine response in the CNS, and
      is partially CCR2 dependent. Conversely, IL-23-modulated, stable Th17 cells
      induce EAE with a relatively mild course via an IL-12-independent pathway. These
      data provide definitive evidence that autoimmune disease can be driven by
      distinct CD4(+) T-helper-cell subsets and polarizing factors. 

PMID- 26220256
TI  - Satellite-Based Spatiotemporal Trends in PM2.5 Concentrations: China, 2004-2013.
AB  - BACKGROUND: Three decades of rapid economic development is causing severe and
      widespread PM2.5 (particulate matter <= 2.5 MUm) pollution in China. However,
      research on the health impacts of PM2.5 exposure has been hindered by limited
      historical PM2.5 concentration data. OBJECTIVES: We estimated ambient PM2.5
      concentrations from 2004 to 2013 in China at 0.1 degrees  resolution using the
      most recent satellite data and evaluated model performance with available ground
      observations. METHODS: We developed a two-stage spatial statistical model using
      the Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 6 aerosol
      optical depth (AOD) and assimilated meteorology, land use data, and PM2.5
      concentrations from China's recently established ground monitoring network. An
      inverse variance weighting (IVW) approach was developed to combine MODIS Dark
      Target and Deep Blue AOD to optimize data coverage. We evaluated model-predicted
      PM2.5 concentrations from 2004 to early 2014 using ground observations. RESULTS:
      The overall model cross-validation R(2) and relative prediction error were 0.79
      and 35.6%, respectively. Validation beyond the model year (2013) indicated that
      it accurately predicted PM2.5 concentrations with little bias at the monthly
      (R(2) = 0.73, regression slope = 0.91) and seasonal (R(2) = 0.79, regression
      slope = 0.92) levels. Seasonal variations revealed that winter was the most
      polluted season and that summer was the cleanest season. Analysis of predicted
      PM2.5 levels showed a mean annual increase of 1.97 MUg/m(3) between 2004 and 2007
      and a decrease of 0.46 MUg/m(3) between 2008 and 2013. CONCLUSIONS: Our satellite
      driven model can provide reliable historical PM2.5 estimates in China at a
      resolution comparable to those used in epidemiologic studies on the health
      effects of long-term PM2.5 exposure in North America. This data source can
      potentially advance research on PM2.5 health effects in China.

PMID- 26220257
TI  - The Effect of Foot Reflexology on Acute Pain in Infants: A Randomized Controlled
      Trial.
AB  - AIM: This study was a randomized controlled trial designed to evaluate the effect
      of foot reflexology applied on infants on acute pain that may arise after vaccine
      injection. METHODS: The sample consisted of 1- to 12-month-old infants registered
      in a family health center in Istanbul, Turkey, for healthcare follow-up. A total
      of 60 infants who met the criteria of the sample group were included in the
      study; 30 infants constituted the reflexology group and the other 30 constituted
      the control group. Although questionnaire forms were used to determine the
      descriptive characteristics of infant-mother pairs, the Face, Legs, Activity,
      Cry, Consolability (FLACC) Pain Assessment Scale was used to evaluate pain level.
      Infants in the reflexology group received reflexology treatment for an average of
      20-30 minutes before vaccination, depending on the physical size of the infant's
      foot. Pain, heart rate, oxygen saturation levels, and crying periods of infants
      in the reflexology and control groups were evaluated before and after
      vaccination. RESULTS: The FLACC pain score was observed to be statistically
      similar between groups. After reflexology was applied to infants in the
      reflexology group before vaccination, it was determined that the pain score was
      reduced to .50 +/- 1.14. In the examination performed after vaccination, FLACC
      pain score was found to be 5.47 +/- 2.11 in the reflexology group and 9.63 +/-
      .85 in the control group. A statistically significant difference was observed
      between the mean FLACC pain scores of infants in the reflexology and control
      groups (p = .000). The infants in the reflexology group also had lower heart
      rates, higher oxygen saturation, and shorter crying periods than the infants in
      the control group (p <.001). LINKING EVIDENCE TO ACTIONS: Reflexology before
      vaccine reduced the pain level experienced after vaccination. Future research
      needs to explore different interventional practices.

PMID- 26220258
TI  - Legionnaires' Disease in Hotels and Passenger Ships: A Systematic Review of
      Evidence, Sources, and Contributing Factors.
AB  - BACKGROUND: Travel-associated Legionnaires' disease (LD) is a serious problem,
      and hundreds of cases are reported every year among travelers who stayed at
      hotels, despite the efforts of international and governmental authorities and
      hotel operators to prevent additional cases. METHODS: A systematic review of
      travel-associated LD events (cases, clusters, outbreaks) and of environmental
      studies of Legionella contamination in accommodation sites was conducted. Two
      databases were searched (PubMed and EMBASE). Data were extracted from 50 peer
      reviewed articles that provided microbiological and epidemiological evidence for
      linking the accommodation sites with LD. The strength of evidence was classified
      as strong, possible, and probable. RESULTS: Three of the 21 hotel-associated
      events identified and four of nine ship-associated events occurred repeatedly on
      the same site. Of 197 hotel-associated cases, 158 (80.2%) were linked to hotel
      cooling towers and/or potable water systems. Ship-associated cases were most
      commonly linked to hot tubs (59/83, 71.1%). Common contributing factors included
      inadequate disinfection, maintenance, and monitoring; water stagnation; poor
      temperature control; and poor ventilation. Across all 30 events, Legionella
      concentrations in suspected water sources were >10,000 cfu/L, <10,000 cfu/L, and
      unknown in 11, 3, and 13 events, respectively. In five events, Legionella was not
      detected only after repeated disinfections. In environmental studies, Legionella
      was detected in 81.1% of ferries (23/28) and 48.9% of hotels (587/1,200), while
      all 12 cruise ships examined were negative. CONCLUSIONS: This review highlights
      the need for LD awareness strategies targeting operators of accommodation sites.
      Increased standardization of LD investigation and reporting, and more rigorous
      follow-up of LD events, would help generate stronger, more comparable evidence on
      LD sources, contributing factors, and control measure effectiveness.

PMID- 26220259
TI  - Serum preadipocyte factor 1 concentrations and risk of developing diabetes: a
      nested case-control study.
AB  - AIM: To determine whether preadipocyte factor 1 could be a predictive marker for
      the development of diabetes in people without diabetes at baseline. METHODS: We
      conducted a population-based, nested case-control study of individuals who
      progressed to diabetes (n = 43) or prediabetes (n = 345) and control participants
      matched on age, sex and fasting plasma glucose concentration, who maintained
      normal glucose tolerance (n = 389) during a 4-year follow-up using data from the
      Chungju Metabolic disease Cohort Study. Circulating levels of preadipocyte factor
      1 were measured using an enzyme-linked immunosorbent assay. RESULTS: Baseline
      serum preadipocyte factor 1 levels showed a stepwise decrease across the glucose
      tolerance status groups at follow-up (normal glucose tolerance: 10.02 +/- 3.02
      ng/ml; prediabetes: 9.48 +/- 3.35 ng/ml; diabetes: 8.66 +/- 3.29 ng/ml; P for
      trend, 0.0151). Individuals whose fasting plasma glucose level had increased or
      whose homeostasis model assessment of beta-cell function had decreased at follow
      up showed significantly lower levels of preadipocyte factor 1 compared with their
      control group counterparts. After adjusting for age, BMI, fasting plasma glucose,
      serum insulin levels, systolic blood pressure and triglycerides, the incidence of
      diabetes was nearly threefold higher in the lowest vs. the upper three quartiles
      of circulating preadipocyte factor 1 (relative risk 2.794; 95% CI 1.188-6.571; P
      = 0.0185). Notably, these findings were significant in women but not in men.
      CONCLUSIONS: Levels of circulating preadipocyte factor 1 may be a useful
      biomarker for identifying women at high risk of developing diabetes.

PMID- 26220260
TI  - CRPS: A contingent hypothesis with prostaglandins as crucial conversion factor.
AB  - CRPS is an acute pain disease expressed as chronic pain with a severe loss of
      tissue and function. CRPS usually occurs after minor injuries and then progresses
      in a way that is scarcely controllable, or completely uncontrollable. This
      article addresses the functional control mechanism of a biological organism, a
      comparison of techniques, and the way the negative feedback mechanisms fail in
      regulated feedback systems. The measurement and regulation system is controlled
      at the local, regional, and central levels in a biological system. Locally
      generated substances such as prostaglandins and hormones, as well as the central
      nervous system, play important roles in this process. Prostaglandins fulfil many
      conversion functions and are involved in vasoactive processes, pain, and
      inflammation. They play an intermediating role between the activity of the
      autonomic nervous system and local occurrences. The insufficiently explored
      conversion function of prostaglandins as a ubiquitously present cofactor may be
      related to the development of CRPS at sites which have had minor injuries in the
      past. RELEVANCE: Chronic Regional Pain Syndrome (CRPS) is a moderately prevalent
      disease, which occurs more frequently with age. Even though there are diseases
      known to have a precipitating effect on the aetiology of CRPS, for example Carpal
      tunnel syndrome, the mechanism of onset is unknown. The disease falls under the
      category of chronic pain, and seldom has an effective treatment based on
      scientific research. The economic and psychosocial aspects of the disease are
      substantial. HYPOTHESIS: CRPS is the final position of a positive feedback
      measurement and control system. BACKGROUND OF THE HYPOTHESIS: Homoeostasis is
      directed by measurement and control processes. In electronics, a rapid conversion
      system, which quickly adapts to changing circumstances, superimposed with a
      delayed conversion system, which ensures a stable basis of homoeostasis. Measured
      changes are compensatorily controlled. An analogy is expected for a Complex
      Adaptive System such as a living organism. Hormonal systems are slow systems,
      suitable for stabilising activity. Neural reflex systems function quickly.
      Prostaglandins that come from local tissue may be the link between the slow and
      rapid control. In electronics, negative feedback can convert into a feedback loop
      which results in the dysregulation, which is what prostaglandins do in
      biochemistry. A dysregulated feedback control mechanism only has two positions: a
      zero position and a final position. The process is not easily influenced by other
      factors. Only phase shifting and signal weakness can affect the feedback process.
      Theoretically, prostaglandins can also affect this process.

PMID- 26220261
TI  - Amyotrophic lateral sclerosis: Is the spinal fluid pathway involved in seeding
      and spread?
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      manifested primarily by loss of upper and lower motor neurons. Current
      explanations for disease progression invoke regional spread attributed to the
      transfer of pathogenic factors among physically contiguous neurons. However, this
      explanation incompletely explains certain clinical and in vitro data. Considering
      this, we propose that the cerebrospinal fluid (CSF) pathway is likely to be a key
      vector for seeding local and distal disease. Subsequent disease progression would
      be expected to occur independently via either axonal or CSF transmission. If one
      accepts the hypothesis that the CSF pathway is involved in ALS progression, it
      follows that the choroid plexus (CP) might well be a driver of the disease
      process. In support of this, we briefly review the anatomical and physiological
      features of the CSF pathway and the choroid plexus responsible for secreting CSF.
      In addition, we draw attention to the interface of the CP and CSF with the immune
      system. We then summarize both clinical and cell culture research that supports a
      key role of the CSF in the establishment and inter-neuronal spread of ALS, and
      which suggest directions for translational research. 

PMID- 26220263
TI  - 11th ETS Special Issue of Reproductive Toxicology: Welcome!

PMID- 26220264
TI  - Determination of blood concentration levels of psychotropic medications in
      Rwandan patients.
AB  - OBJECTIVES: In Rwanda, no therapeutic monitoring of psychotropic drugs is done.
      This results in difficult treatment optimisation and exposition to a high risk of
      toxicity and drug ineffectiveness for patients under treatment. This study aimed
      to determine blood concentration levels of psychotropic drugs in Rwandan patients
      and identify problems associated with the lack of therapeutic drug monitoring
      (TDM) of these drugs. METHODS: The analysis was performed on 1 ml of serum sample
      using prazepam as internal standard. Regarding the step of sample preparation, we
      used a liquid-liquid extraction with a mixture of organic solvents: diethyl
      ether/dichloromethane/hexane/n-amyl alcohol (50/30/20/0.5:V/V). A Waters Alliance
      2695 was used for analysis. The chromatography was run on a Symmetry C8 column
      and as mobile phase acetonitrile and phosphate buffer (pH 3.8) were used.
      RESULTS: Concerning the results, serum samples from 128 patients were analysed.
      Twenty-one different psychotropic drugs belonging to various pharmacological
      classes were detected and quantified. Analytical results were put into three
      categories based upon therapeutic reference ranges (TRR) of various drugs:
      subtherapeutic, therapeutic and supratherapeutic. For a total of 237 analyses,
      results within TRR represented 46% while 47 and 8% of results were, respectively,
      below and above TRR. CONCLUSION: It was therefore concluded that patients under
      psychotropic treatment in Rwanda are exposed to both the risk of drug
      ineffectiveness and the risk of toxicity (54%) with only 46% of results within
      the TRR. Consequently, TDM is needed to optimise psychotropic treatment in
      Rwandan patients.

PMID- 26220265
TI  - Galanin receptors as a potential target for neurological disease.
AB  - INTRODUCTION: Galanin is a 29/30 amino acid long neuropeptide that is widely
      expressed in the brains of many mammals. Galanin exerts its biological activities
      through three different G protein-coupled receptors, GalR1, GalR2 and GalR3. The
      widespread distribution of galanin and its receptors in the CNS and the various
      physiological and pharmacological effects of galanin make the galanin receptors
      attractive drug targets. AREAS COVERED: This review provides an overview of the
      role of galanin and its receptors in the CNS, the involvement of the galaninergic
      system in various neurological diseases and the development of new galanin
      receptor-specific ligands. EXPERT OPINION: Recent advances and novel approaches
      in migrating the directions of subtype-selective ligand development and chemical
      modifications of the peptide backbone highlight the importance of the galanin
      neurochemical system as a potential target for drug development.

PMID- 26220266
TI  - Assessment of the relationships among coagulopathy, hyperfibrinolysis, plasma
      lactate, and protein C in dogs with spontaneous hemoperitoneum.
AB  - OBJECTIVE: To relate coagulation and fibrinolysis derangements to shock severity
      as reflected by plasma lactate concentrations in dogs with spontaneous
      hemoperitoneum (SHP) and determine the impact on transfusions. DESIGN:
      Prospective, observational, case-control study. SETTING: Three veterinary
      teaching hospitals. ANIMALS: Twenty-eight client-owned dogs with SHP and 28 breed
      and age-matched control dogs. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Blood samples for platelet counts, coagulation, and anticoagulant assays
      (prothrombin time, activated partial thromboplastin time, fibrinogen,
      antithrombin, and protein C, thromboelastography [TEG]), fibrinolysis testing (d
      dimer and TEG lysis parameters with and without the addition of 50 U/mL of tissue
      plasminogen activator [TEG LY30 measured with the addition of 50 U/mL of tPA to
      the blood sample, LY3050 and TEG LY60 measured with the addition of 50 U/mL of
      tPA to the blood sample, LY6050 ; LY30 and LY60]), and plasma lactate as an
      indicator of severity of shock were collected from SHP dogs at the time of
      diagnosis. SHP dogs were hypocoagulable (prolonged prothrombin time and activated
      partial thromboplastin time, decreased TEG maximum amplitude) and
      hyperfibrinolytic (increased LY3050 and TEG LY6050 ) compared to controls. The
      severity of hypocoagulability was related to protein C activity, while the
      severity of hyperfibrinolysis was related to plasma lactate concentration. Among
      the 18 dogs discharged from the hospital, LY3050 was significantly associated
      with the dose of fresh frozen plasma administered, but none of the parameters
      were associated with the dose of red blood cells administered. CONCLUSIONS: Dogs
      with SHP have evidence of hypocoagulability, protein C deficiency, and
      hyperfibrinolysis. Parameters of hyperfibrinolysis were related to plasma lactate
      concentrations and volume of plasma transfused during hospitalization. These
      derangements resemble those found in people with acute coagulopathy of trauma and
      shock, and activation of protein C may be a common feature to both syndromes.

PMID- 26220268
TI  - An inability to set independent attentional control settings by hemifield.
AB  - Recent evidence suggests that people can simultaneously activate attentional
      control setting for two distinct colors. However, it is unclear whether both
      attentional control settings must operate globally across the visual field or
      whether each can be constrained to a particular spatial location. Using two
      different paradigms, we investigated participants' ability to apply independent
      color attentional control settings to distinct regions of space. In both
      experiments, participants were told to identify red letters in one hemifield and
      green letters in the opposite hemifield. Additionally, some trials used a
      "relevant distractor"-a letter that matched the opposite side's target color. In
      Experiment 1, eight letters appeared (four per hemifield) simultaneously for a
      brief amount of time and then were masked. Relevant distractors increased the
      error rate and resulted in a greater number of distractor intrusions than
      irrelevant distractors. Similar results were observed in Experiment 2 in which
      red and green targets were presented in two rapid serial visual presentation
      streams. Relevant distractors were found to produce an attentional blink similar
      in magnitude to an actual target. The results of both experiments suggest that
      letters matching either attentional control setting were selected by attention
      and were processed as if they were targets, providing strong evidence that both
      attentional control settings were applied globally, rather than being constrained
      to a particular location. 

PMID- 26220267
TI  - Prognostic value of (18)F-fluorodeoxyglucose PET-CT imaging in acute aortic
      syndromes: comparison with serological biomarkers of inflammation.
AB  - Aim of this study was to investigate the relationship between (18)F
      fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET
      CT) findings and serological biomarkers of inflammation and the related
      discriminant value of unfavourable outcome during follow-up in patients with
      acute aortic syndromes (AAS). Sixty patients with AAS underwent PET-CT imaging
      during the hospitalization along with measurement of C-reactive protein (CRP) and
      D-dimer (D-d) serum levels. An aortic wall pathology was considered PET-positive
      by a maximum standardized uptake value (SUVmax) >2.5. A combined endpoint of
      major adverse events (MAE) including aorta-related mortality, disease progression
      and re-intervention was used to compare patient subgroups at 3-year follow-up.
      PET-CT detected an elevated FDG uptake within the aortic wall in 25 (41.7%)
      patients. PET-positive patients showed significantly increased CRP levels (10.0
      +/- 6.6 mg/dL) and tended to higher D-d levels (5.1 +/- 3.9 mg/L), compared to
      PET-negative patients (5.8 +/- 6.1 mg/dL and 3.1 +/- 4.7 mg/L respectively; P =
      0.048, P = 0.19). At 3-year follow-up, all-cause mortality and MAE were higher in
      the PET-positive (21.7 and 47.8% respectively) than PET-negative group (0.0 and
      13.3% respectively; P = 0.012, P = 0.006). On Kaplan-Meier analysis, PET-positive
      patients were at higher risk of MAE (P = 0.031). This tendency was more evident
      by combining PET results with D-d levels at a cutoff value of 4.8 mg/L (P <
      0.001). In patients with AAS, a pathological glucose uptake in aortic wall
      lesions by PET-CT was associated with high CRP levels and increased mortality and
      MAE at 3-year follow-up. The combination of PET results with D-d levels had the
      best discriminant value of MAE.

PMID- 26220269
TI  - Multiscale anode materials in lithium ion batteries by combining micro- with
      nanoparticles: design of mesoporous TiO2 microfibers@nitrogen doped carbon
      composites.
AB  - TiO2 has been considered as a promising anode material for lithium ion batteries.
      However, its poor rate capability originating from the intrinsically low lithium
      ion diffusivity and its poor electronic conductivity hampers putting such an
      application into practice. Both issues can be addressed by nanostructure
      engineering and conductive surface coating. Herein, we report a template-assisted
      synthesis of micron sized TiO2 fibers consisting of a mesoporous network of
      anatase nanoparticles of about 7.5 nm and coated by N doped carbon. In a first
      step, an amorphous layer of TiO2 was deposited on cobalt silicate nanobelts and
      subsequently transformed into crystalline anatase nanoparticles by hydrothermal
      treatment. The N doped carbon coating was realized by in situ polymerization of
      dopamine on the crystalline TiO2 followed by annealing under N2. After removal of
      the template, we obtained the final mesoporous TiO2 fibers@N doped carbon
      composite. Electrochemical tests revealed that the composite electrode exhibited
      excellent electrochemical properties in terms of specific capacity, rate
      performance and long term stability. 

PMID- 26220270
TI  - Association between red cell distribution width and risk of venous
      thromboembolism.
AB  - BACKGROUND: An association between high red cell distribution width (RDW) and
      venous thromboembolism (VTE) has been observed. However, it is not known whether
      this association differs within various manifestations of VTE, nor if there is an
      interaction between RDW and thrombophilia abnormalities on the risk of VTE. AIMS:
      To investigate whether RDW is a marker of the risk of VTE; to identify subgroups
      of patients in which the association between RDW and VTE is stronger; to
      investigate a possible interaction between RDW and thrombophilia abnormalities.
      METHODS: Case-control study on 730 patients with a first objectively-confirmed
      VTE episode (300 unprovoked and 430 provoked) consecutively referred to our
      Center between 2007 and 2013, and 352 healthy controls. Blood was taken for a
      thrombophilia work-up and a complete blood count, including RDW, at least three
      months after VTE. RESULTS: Individuals with RDW above the 90(th) percentile
      (>14.6%) had a 2.5-fold increased risk of VTE compared to those with RDW <=90(th)
      percentile, independently of age, sex, body mass index, other hematological
      variables and renal function (adjusted odds ratio: 2.52 [95%CI:1.42-4.47]). The
      risk was similar for unprovoked and provoked VTE, and slightly higher in patients
      with pulmonary embolism (adjusted odds ratio 3.19 [95%CI:1.68-6.09]) than in
      those with deep vein thrombosis alone (2.29 [95%CI:1.22-4.30]). No interaction
      between high RDW and thrombophilia abnormalities on the risk of VTE was observed.
      CONCLUSION: Our findings confirm RDW as an independent and easily available
      marker for stratification of the risk of VTE.

PMID- 26220271
TI  - Thrombosis in vasculitic disorders-clinical manifestations, pathogenesis and
      management.
AB  - Inflammation and coagulation are known to affect each other in many ways.
      Vasculitis represents a group of disorders where blood vessels (small, medium,
      large or variable) are infiltrated with inflammatory cells. Accumulating evidence
      in the literature suggests both clinical and physiological association between
      vasculitis and thrombosis. Vasculitis-associated thrombosis involves arteries and
      veins, and a tight connection has been reported between the activity of
      vasculitis and the appearance of thrombosis. Pathophysiology of these relations
      is complex and not completely understood. While thrombophilic factors are
      associated with vasculitis, it remains unclear whether a true association with
      clinical thrombosis is present. Furthermore, several factors leading to
      hemostasis, endothelial injury and induction of microparticles were described as
      possibly accounting for thrombosis. Management of thrombosis in vasculitis
      patients is challenging and should be further assessed in randomized controlled
      studies. The current review describes clinical manifestations, pathogenesis and
      management of thrombosis associated with different vasculitides. 

PMID- 26220273
TI  - Assessing Molecular Dynamics Simulations with Solvatochromism Modeling.
AB  - For the modeling of solvatochromism with an explicit representation of the
      solvent molecules, the quality of preceding molecular dynamics simulations is
      crucial. Therefore, the possibility to apply force fields which are derived with
      as little empiricism as possible seems desirable. Such an approach is tested here
      by exploiting the sensitive solvatochromism of p-nitroaniline, and the use of
      reliable excitation energies based on approximate second-order coupled cluster
      results within a polarizable embedding scheme. The quality of the various MD
      settings for four different solvents, water, methanol, ethanol, and
      dichloromethane, is assessed. In general, good agreement with the experiment is
      observed when polarizable force fields and special treatment of hydrogen bonding
      are applied. 

PMID- 26220272
TI  - Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection
      for Enhanced Muscle Gene Transfer.
AB  - A major hindrance in gene therapy trials with adeno-associated virus (AAV)
      vectors is the presence of neutralizing antibodies (NAbs) that inhibit AAV
      transduction. In this study, we used directed evolution techniques in vitro and
      in mouse muscle to select novel NAb escape AAV chimeric capsid mutants in the
      presence of individual patient serum. AAV mutants isolated in vitro escaped broad
      patient-specific NAb activity but had poor transduction ability in vivo. AAV
      mutants isolated in vivo had enhanced NAb evasion from cognate serum and had high
      muscle transduction ability. More importantly, structural modeling identified a
      100 amino acid motif from AAV6 in variable region (VR) III that confers this
      enhanced muscle tropism. In addition, a predominantly AAV8 capsid beta barrel
      template with a specific preference for AAV1/AAV9 in VR VII located at threefold
      symmetry axis facilitates NAb escape. Our data strongly support that chimeric AAV
      capsids composed of modular and nonoverlapping domains from various serotypes are
      capable of evading patient-specific NAbs and have enhanced muscle transduction. 

PMID- 26220274
TI  - Effects of background anionic compounds on the activity of the hammerhead
      ribozyme in Mg(2+)-unsaturated solutions.
AB  - Cellular ribozymes exhibit catalytic activity in media containing large numbers
      of anionic compounds and macromolecules. In this study, the RNA cleavage activity
      of the hammerhead ribozyme induced by Mg(2+) was investigated using the solutions
      containing background nucleic acids, small phosphate and carboxylic acid
      compounds, and neutral polymers. Analysis of the substrate cleavage kinetics
      showed that the anionic compounds do not affect the ribozyme activity in Mg(2+)
      saturated solutions and there is almost no effect of the anion-Mg(2+) complexes
      formed. On the other hand, the rate of substrate cleavage in Mg(2+)-unsaturated
      solutions was reduced under conditions of a high background of anionic compounds
      found in cells. The extent of the reduction was more with a greater net negative
      charge, caused by decreased amounts of Mg(2+) that could be used for the ribozyme
      reaction. It was remarkable that background DNA and RNA molecules having
      phosphodiester bonds reduced the cleavage rate as much as adenosine
      monophosphates having a charge of -2 when the effects of the same amount of
      phosphate groups were compared. Greater reductions in rates than those expected
      from the molecular charge were also observed in the background of fatty acids
      that form micelles. An addition of poly(ethylene glycol) to the solutions
      partially restored the ribozyme activity, suggesting a possible role of
      macromolecular crowding in counteracting the inhibitory effects of background
      anions on the ribozyme reaction. The results have biological and practical
      implications with respect to the effects of molecular environment on the
      efficiency of ion binding to RNA. 

PMID- 26220275
TI  - Strain differences in temporal changes of nesting behaviors in C57BL/6N, DBA/2N,
      and their F1 hybrid mice assessed by a three-dimensional monitoring system.
AB  - Nest building is one of the innate behaviors that are widely observed throughout
      the animal kingdom. Previous studies have reported specific brain regions and
      genetic loci associated with nest building in mice. These studies mainly
      evaluated the nest structure, without observing the nesting process. In this
      study, we evaluated the effects of strain and learning on the nesting process of
      mice using a 3D depth camera. To determine the quality of the nest structure, a
      conventional scoring method, Deacon scores 1-5, was applied to the recorded depth
      images. The final score of the nest, latency to start nesting behavior, and
      latencies to reach Deacon scores 3-5, were determined using three genetically
      different mouse strains-C57BL/6NCrl (B6), DBA/2NCrlCrlj (DBA), and B6D2F1/Crl
      (B6D2F1). The final score of the DBA nest was significantly lower than that of
      the B6D2F1 nest, and DBA mice showed significantly longer latency to start nest
      building than the other two strains in the first trial. By observing the time
      course of nest building, we confirmed that DBA mice took significantly longer to
      build their nests than B6 and B6D2F1 mice. Although we did not find any
      significant differences between DBA and B6 mice in the final assessment of the
      nest based on the Deacon method, overnight monitoring of the nesting behavior
      using a 3D depth camera could elucidate the clear differences in the amount of
      time spent nesting between DBA and B6 mice. In addition, the learning effect was
      more evident in DBA mice than it was in B6 in terms of latencies to reach Deacon
      score 3-5 in five repeated trials. DBA mice showed a gradual decrease in latency
      to build, whereas nesting behaviors of B6 mice were relatively consistent
      throughout the five trials. Therefore, our 3D depth image method gives higher
      resolution and structural information regarding the nesting process in mice.
      Future genetic analyses using the 3D assessment system will provide novel
      insights into the complex genetic basis for nesting and other behaviors in
      animals. 

PMID- 26220276
TI  - Hydroxoiridium/Chiral Diene Complexes as Effective Catalysts for Asymmetric
      Annulation of alpha-Oxo- and Iminocarboxamides with 1,3-Dienes.
AB  - The asymmetric [3+2] annulation of alpha-oxo- and alpha-iminocarboxamides with
      1,3-dienes catalyzed by hydroxoiridium/chiral diene complexes was realized,
      giving high yields of the corresponding gamma-lactams with high
      enantioselectivity. 

PMID- 26220277
TI  - HPV Vaccine Public Awareness Campaigns: An Environmental Scan.
AB  - Human papillomavirus (HPV) vaccination rates are significantly lower than
      recommended targets. Public awareness campaigns can raise awareness of the
      severity and prevalence of HPV infection and the cancer prevention benefits of
      the vaccine. We conducted an environmental scan of HPV vaccine public awareness
      campaigns during the summer of 2014. We used online search strategies and expert
      input to identify candidate campaigns. Multiple study investigators reviewed all
      data abstraction and analysis. After applying our inclusion criteria, we
      identified 14 campaigns with parents or teenagers as the target audience. We
      characterized campaign messages according to constructs of the Health Belief
      Model. Most messages focused on the cancer prevention benefits of HPV vaccine;
      few addressed psychological or practical barriers to getting or completing the
      vaccine. Four of 14 campaigns had pre- or postcampaign data readily available,
      only 2 used vaccine outcomes in their evaluations. We concluded there was a high
      prevalence of HPV vaccine public awareness campaigns but little available
      evidence on their impact on intermediate or vaccine outcomes. 

PMID- 26220278
TI  - Vending Assessment and Program Implementation in Four Iowa Worksites.
AB  - The worksite food environment, including vending options, has been explored as an
      important contributor to dietary decisions made every day. The current study
      describes the vending environment, and efforts to change it, in four Iowa
      worksites using a series of case studies. Data were gathered by local
      coordinators as part of the Iowa Community Transformation Grant project. Data
      were collected from three sources. First, the Nutrition Environment Measures
      Survey-Vending was used to assess healthy vending options in worksite machines
      before and after the intervention. Second, employee vending behavior was
      evaluated with a pre-, post-intervention survey. Items assessed attitudes and
      behaviors regarding vending, plus awareness and reaction to intervention
      activities. Third, program coordinators documented vending machine intervention
      strategies used, such as social marketing materials and product labels. The
      Nutrition Environment Measures Survey-Vending documented that the majority of
      vending options did not meet criteria for healthfulness. The vending survey found
      that employees were generally satisfied with the healthier items offered. Some
      differences were noted over time at the four worksites related to employee
      behavior and attitudes concerning healthy options. There were also differences in
      intervention implementation and the extent of changes made by vending companies.
      Overall, findings demonstrate that a large percentage of employees are
      constrained in their ability to access healthy foods due to limited worksite
      vending options. There also remain challenges to making changes in this
      environment. Findings have implications for public health practitioners to
      consider when designing healthy vending interventions in worksites. 

PMID- 26220279
TI  - Partnering With Community-Dwelling Individuals With Diabetes for Health Behavior
      Change Using Action Plans: An Innovation in Health Professionals Education and
      Practice.
AB  - Health care practitioners support or hinder an individual's attempts to self
      manage health behavior. Practitioners must understand an individual's health
      needs and goals to effectively partner for behavior change. Self-management
      support (SMS) promote efforts toward positive health behavior change.
      Practitioners need training to provide effective SMS, beginning with their formal
      education. The purpose of this educational practice project was to integrate an
      evidence-based intervention (SMS using action plans) into a nursing curriculum.
      Three sequential steps included (1) providing foundational SMS education, (2) SMS
      application with students' personal action plans, and (3) implementing SMS with
      community-dwelling individuals with diabetes. Students (n = 130) partnered with
      participants (n = 85), developing short- (n = 240) and long-term (n = 99) action
      plans during home visits. The average baseline Diabetes Empowerment Scale score
      measuring participant's perceived psychosocial diabetes management self-efficacy
      was 4.3 (1-5 scale, SD = 0.51, n = 83). Most common short-term actions related to
      physical activity (n = 100, 42%) and healthy eating (n = 61, 25%). Average
      participant confidence level was 7.7 (SD = 1.9, 0-10 scale). Short-term goal
      evaluation (n = 209) revealed 66% (n = 137) were met more than 50% of the time.
      Both participants (99%) and students (99%) expressed satisfaction with home visit
      and action plan experiences. This teaching-learning experience is replicable and
      applicable to any professional health care student. 

PMID- 26220280
TI  - Advocacy, Efficacy, and Engagement in an Online Network for Latino Childhood
      Obesity Prevention.
AB  - Salud America! is a national network created to engage Latino researchers, health
      professionals and community leaders in actions to reduce Latino childhood
      obesity. An online survey of 148 Salud America! network members investigated
      relationships between (1) their levels of engagement with the network, (2) self-
      and collective-efficacy, and (3) behavioral intentions to engage in advocacy for
      policies that can help reduce Latino childhood obesity. Analyses of these data
      found that higher levels of Salud America! engagement was associated with
      collective-advocacy efficacy-greater confidence in organized group advocacy as a
      way of advancing policies to reduce Latino childhood obesity. A multiple
      regression analysis found that this sense of collective-efficacy moderately
      predicted intentions to engage in advocacy behaviors. Salud America! engagement
      levels were less strongly associated with members' confidence in their personal
      ability to be an effective advocate, yet this sense of self-efficacy was a very
      strong predictor of a behavioral intention to advocate. Based on these findings,
      new online applications aimed at increasing self- and collective-efficacy through
      peer modeling are being developed for Salud America! in order to help individuals
      interested in Latino childhood obesity prevention to connect with each other and
      with opportunities for concerted local actions in their communities. 

PMID- 26220281
TI  - Perspectives From the Field: Certified Health Education Specialists on the Value
      of Health Education Credentialing.
AB  - In this commentary, four Certified Health Education Specialists (CHESs) share
      their reasons for obtaining national certification as health education
      specialists, the value of national credentialing to their employers, and the
      career development benefits of National Commission for Health Education
      Credentialing certification. CHESs play a vital role in diverse research and
      practice settings and increasingly contribute to changes in practice and policy
      that promote health equity. National Commission for Health Education
      Credentialing certification enhances our individual capacity as public health
      educators and also enhances our profession through systematic verification of
      responsibilities, competencies, and subcompetencies. This commentary is
      particularly timely in light of the Health Education Specialist Practice Analysis
      2015, which updated, refined, and validated the model of health education
      practice. 

PMID- 26220282
TI  - Inhibitory effect of Phyllanthus urinaria L. extract on the replication of
      lamivudine-resistant hepatitis B virus in vitro.
AB  - BACKGROUND: Long-term treatment of chronic hepatitis B (CHB) with nucleos(t)ide
      analogs results in the emergence of drug-resistant hepatitis B virus (HBV)
      harboring mutations in the polymerase (P) gene. The Phyllanthus extract has anti
      HBV activity; however, its antiviral activity against lamivudine (LMV)-resistant
      mutants has not been examined. METHODS: HBV harboring LMV-resistant mutations
      (rtM204I, rtM204V, and rtM204S) in the P gene at the YMDD ((203)tyrosine
      methionine-aspartate-aspartate(206)) reverse transcriptase (RT) active site were
      generated and their sensitivity to Phyllanthus urinaria koreanis extract
      examined. Southern blotting and real-time PCR were used to determine the
      concentration of plant extract required to inhibit HBV DNA synthesis by 50 and
      90% (EC50 and EC90, respectively). An enzyme-linked immunosorbent assay was used
      to measure the EC50 of HBV surface antigen (HBsAg) and HBV core antigen (HBcAg)
      secretion, and the 50% cytotoxic concentration of the extract was measured in a 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Real-time RT
      PCR was used to measure mRNA expression levels. RESULTS: The expression of
      intracellular HBV DNAs in HBV WT- or mutant-transfected HepG2 cells decreased
      upon treatment with Phyllanthus extract. The secretion of HBsAg and HBcAg also
      fell in a dose-dependent manner. Phyllanthus extract induced interferon-beta (IFN
      beta), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6) mRNA expression in HBV
      WT-transfected HepG2 cells, possibly via activation of extracellular signal
      regulated kinases and c-jun N-terminal kinases and the induction of retinoic acid
      inducible gene-I, toll-like receptor 3, myeloid differentiation primary response
      gene 88, and/or tumor necrosis factor receptor-associated factor 6 gene
      expression. HBV transfection in the absence of extract or exposure of cells to
      extract alone did not trigger these signaling cascades. CONCLUSIONS: Phyllanthus
      extract inhibited HBV DNA synthesis and HBsAg and HBcAg secretion by replicating
      cells harboring HBV wild-type and LMV-resistant mutants, likely by inducing the
      expression of IFN-beta, COX-2, and IL-6. These data indicate that Phyllanthus
      extract may be useful as an alternative therapeutic agent for the treatment of
      drug-resistant CHB patients.

PMID- 26220283
TI  - Multicenter, randomized, tandem evaluation of EndoRings colonoscopy--results of
      the CLEVER study.
AB  - BACKGROUND AND STUDY AIMS: Adenoma miss rate during colonoscopy has become a
      widely acknowledged proxy measure for post-colonoscopy colorectal cancer. Among
      other reasons, this can happen because of inadequate visualization of the
      proximal aspects of colonic folds and flexures. EndoRings (EndoAid Ltd.,
      Caesarea, Israel) is a silicone-rubber device that is fitted onto the distal end
      of the colonoscope. Its flexible circular rings engage and mechanically stretch
      colonic folds during withdrawal. The primary aim of this study was to compare
      adenoma miss rates between standard colonoscopy and colonoscopy using EndoRings.
      METHODS: In this multicenter, randomized, tandem colonoscopy study, we performed
      same-day, back-to-back colonoscopies with EndoRings followed by standard
      colonoscopy, or vice versa. RESULTS: After exclusion of 10 patients for protocol
      violations, 116 patients (38.8% female; mean age 58.7) remained for analysis. The
      adenoma miss rate of EndoRings colonoscopy (7/67; 10.4%) was significantly lower
      (P<0.001) compared with standard colonoscopy (28/58; 48.3%). Similar results were
      found for polyp miss rates: EndoRings (9.1%) and standard colonoscopy (52.8%;
      P<0.001). Mean cecal intubation times (9.3 vs. 8.4 minutes; P=0.142) and
      withdrawal times (7.4 vs. 7.2 minutes; P=0.286), respectively, were not
      significantly different between EndoRings and standard colonoscopy. Mean total
      procedure time was longer with EndoRings than with standard colonoscopy (21.6 vs.
      18.5 minutes, P=0.001) as more polyps were removed. CONCLUSIONS: This study
      demonstrates that colonoscopy with EndoRings has lower adenoma and polyp miss
      rates than standard colonoscopy, which may improve the efficacy particularly of
      screening and surveillance colonoscopies. ClinicalTrials.gov NCT01955122.

PMID- 26220284
TI  - Risk of stricture after endoscopic submucosal dissection for large rectal
      neoplasms.
AB  - BACKGROUND AND STUDY AIMS: Improvements in the endoscopic submucosal dissection
      (ESD) technique have made circumferential ESD in the rectum possible. However,
      little is known about the clinical course after extensive ESD in the rectum. The
      aim of this study was to determine the stricture risk in the rectum after total
      or subtotal circumferential ESD. PATIENTS AND METHODS: A total of 69 patients
      with 69 rectal tumors that required >= 75 % circumferential resection were
      identified at Kobe University Hospital and an affiliated hospital between April
      2005 and May 2014. Among the patients, 61 were available for evaluation of
      stricture development, either by follow-up colonoscopy or by surgical specimens.
      The rate and possible risk factors of post-ESD strictures were investigated.
      RESULTS: Post-ESD rectal strictures developed in 12 patients (19.7 %). Patients
      who underwent total circumferential ESD developed a stricture (5/7, 71.4 %) more
      frequently than those with subtotal (>= 90 %) ESD (7/16, 43.8 %). Patients
      undergoing an ESD procedure that involved < 90 % of the circumference did not
      develop strictures. The strictures were membranous or < 10 mm long in all cases.
      Of the patients with stricture, 11 received endoscopic balloon dilation and one
      received bougie with short-caliber-tip transparent hood; all strictures improved
      following dilation therapy. Statistical analysis revealed that >= 90 %
      circumferential resection was an independent risk factor for stricture, whereas
      morphology and size were not. CONCLUSIONS: Patients who underwent total or
      subtotal circumferential ESD of a rectal tumor had a high risk of stricture
      formation. Dilation helped to alleviate the stenosis.Study registered at
      University Hospital Medical Information Network (UMIN 000016559).

PMID- 26220285
TI  - Assessment of Pharmaceutical Powder Flowability using Shear Cell-Based Methods
      and Application of Jenike's Methodology.
AB  - Jenike's approach to hopper design for a large-scale (3150 L) conical hopper was
      applied to pharmaceutical powders to evaluate flow issues, such as funnel flow or
      cohesive arching. Seven grades of microcrystalline cellulose (MCC) and six powder
      blends were tested. A Schulze Ring Shear Tester measured the flow function, wall
      friction (using stainless steel coupons with a #2B or #8 finish) and
      compressibility. Hopper Index (HI, maximum hopper angle required for mass flow)
      and Arching Index (AI, minimum hopper outlet size to prevent cohesive arch
      formation) were computed using Mathcad((c)) . For MCC, a linear relationship was
      observed between median particle size and the Jenike flow function coefficient. A
      curvilinear relationship was observed for powder blends indicating more complex
      flow behavior than based on median particle size alone. Powder bulk density had a
      minimal effect on AI for MCC grades. Overestimation of AI can occur with this
      method for pharmaceutical powders because the true shape of the flow function is
      not defined at very low consolidation pressures and linear extrapolation becomes
      unrepresentative. This instrumental limitation underscores the need for a precise
      and accurate test method to determine powder flow functions at very low levels of
      consolidation stress for pharmaceutical applications.

PMID- 26220287
TI  - High burden of STI and HIV in male sex workers working as internet escorts for
      men in an observational study: a hidden key population compared with female sex
      workers and other men who have sex with men.
AB  - BACKGROUND: Male sex work in the western countries has changed, including now a
      subculture of male sex workers who have paid sex with men arranged for via the
      internet. The men involved in this subculture do not easily identify themselves
      as sex workers nor as homosexual, and are therefore missed by regular health care
      and public health interventions. These male sex workers may form a hidden key
      population for sexually transmitted infections (STIs) and HIV, bridging towards
      other persons outside this context. METHODS: This clinic-based observational
      study included consultations by male sex workers (n = 212), female sex workers (n
      = 801) and in men having sex with men who did not report being paid for sexual
      contacts (MSM, n = 2703) who received STI and HIV testing and counselling at our
      clinic during the study period. In this study we compare the consultations in
      male sex workers to those in in female sex workers and MSM. Demographic
      characteristics and sexual behaviour of the male sex workers, female sex workers
      and MSM were compared using chi-square tests and non-parametric tests. Using
      univariate and multivariate regression analyses, determinants for STI positivity
      in male sex workers were evaluated. RESULTS: Male sex workers tested positive for
      STI (including HIV) in 40 % of the consultations; female sex workers and MSM
      respectively in 9 and 14 % of the consultations. A new HIV infection was found in
      8 % of the consultations of male sex workers. Male sex workers were a young
      population of migrant sex workers from Eastern Europe. They reported more often
      to also have sex contacts with women and other sex workers. Male sex workers are
      at a higher risk for one or more new STI than female sex workers and other MSM,
      even after correction for age, ethnicity, known HIV positivity and behavioural
      variables. CONCLUSIONS: Male sex workers form a hidden key population that
      impacts the transmission of STI and HIV within the MSM population and, possibly,
      to the heterosexual population. They require specific targeted interventions.
      Although targeting male sex workers is labour intensive it is feasible and
      important to reduce STI transmission.

PMID- 26220286
TI  - The rapid antidepressant effect of ketamine in rats is associated with down
      regulation of pro-inflammatory cytokines in the hippocampus.
AB  - OBJECTIVES: Active inflammatory responses play an important role in the
      pathogenesis of depression. We hypothesized that the rapid antidepressant effect
      of ketamine is associated with the down-regulation of pro-inflammatory mediators.
      METHODS: Forty-eight rats were equally randomized into six groups (a control and
      five chronic unpredictable mild stress (CUMS) groups) and given either saline or
      10 mg/kg ketamine, respectively. The forced swimming test was performed, and the
      hippocampus was subsequently harvested for the determination of levels of
      interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha (TNF-alpha),
      indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), and tryptophan (TRP).
      RESULTS: CUMS induced depression-like behaviours and up-regulated the hippocampal
      levels of IL-1beta, IL-6, TNF-alpha, IDO, and the KYN/TRP ratio, which were
      attenuated by a sub-anaesthetic dose of ketamine. CONCLUSION: CUMS-induced
      depression-like behaviours are associated with a reduction in hippocampal
      inflammatory mediators, whereas ketamine's antidepressant effect is associated
      with a down-regulation of pro-inflammatory cytokines in the rat hippocampus.

PMID- 26220288
TI  - Ear wax.

PMID- 26220289
TI  - Influence of HLA Mismatching on Survival in Lung Transplantation.
AB  - BACKGROUND: Data on human leukocyte antigen (HLA) mismatching and survival after
      lung transplantation (LTx) are variable. METHODS: The UNOS database was queried
      from 1987 to 2013 to examine survival associated with total HLA mismatch >=3 and
      mismatches of 2 at A, B, and DR loci. RESULTS: Of 23,528 first-time, adult LTx
      recipients, 23,384 were included in the univariate Cox analysis, 19,944 in the
      Kaplan-Meier survival function evaluation, and 16,224 in the multivariate Cox
      models. Adjusted models found that the total HLA mismatch >=3 increased the
      mortality hazard [hazard ratio (HR) 1.214; 95% confidence interval (95% CI)
      1.073, 1.374; p = 0.002]. Both HLA-A (HR 1.070; 95% CI 1.023, 1.119; p = 0.003)
      and HLA-DR (HR 1.053; 95% CI 1.007, 1.101; p = 0.024) were associated with
      increased mortality risk, but HLA-B (HR 1.006; 95% CI 0.958, 1.056; p = 0.805)
      was not. Older age, higher creatinine, and higher body mass index were associated
      with increased risk for death. More recent lung transplant and longer ischemic
      time were associated with reduced mortality risk. Induction with basiliximab at
      time of transplant was beneficial by significantly decreasing the risk of death
      (HR 0.846; 95% CI 0.786, 0.909; p < 0.001). CONCLUSIONS: HLA mismatching is
      associated with increased hazard risk for death after LTx, while induction with
      basiliximab and other factors related to LTx reduce the risk.

PMID- 26220291
TI  - Specific ion effects on the hydrophobic interaction of benzene self-assembled
      monolayers.
AB  - The interaction of aromatic compounds with various ions in aqueous solutions
      plays a role in a number of fields, as diverse as protein folding and enhanced
      oil recovery, among others. Therefore, we have investigated the effect of the
      four electrolytes, KCl, NaCl, MgCl2 and CaCl2, on the hydrophobic interaction of
      benzene self-assembled monolayers. Using the jump to contact phenomenon of an
      atomic force microscope (AFM) tip as an indicator of attractive forces between
      the surfaces of a sample and the tip, we discovered lower frequencies in the snap
      in as well as narrower distributions for the snap in distance for the monovalent
      ions, especially for K(+), compared with the behaviour for the divalent ions.
      These observations are explained by the accumulation of charge at the surface by
      cation-pi interactions and an influence of the ions on the formation of
      capillaries that bridge the tip to the surface. Bridging capillaries, i.e.
      nanometre scale gas bubbles, are some of the factors contributing to the long
      range hydrophobic interaction. The results demonstrate how ions influence the
      attraction of hydrophobic entities in aqueous solutions. 

PMID- 26220290
TI  - Comparative efficacy of experimental inactivated and live-attenuated chimeric
      porcine circovirus (PCV) 1-2b vaccines derived from PCV1 and PCV2b isolates
      originated in China.
AB  - BACKGROUND: Porcine circovirus type-2b (PCV2b) is recognized as the etiological
      agent of the various clinical manifestations of porcine circovirus-associated
      disease (PCVAD). Previous studies have demonstrated effectiveness of chimeric
      PCV1-2 vaccines against PCV2b challenge. In this study, the efficacy of
      inactivated and live-attenuated (2 * 10(3.5) or 2 * 10(4.0) 50% tissue culture
      infective dose [TCID50] dose) chimeric PCV1-2b vaccines was compared side-by-side
      in conventional pigs. METHODS: Twenty-seven non-PCV2 viremic pigs without PCV2
      specific antibody were randomly divided into six groups, including four
      vaccinated and challenged groups, a nonvaccinated challenged group, and a mock
      group. All pigs except those in the mock group were challenged at 28 days post
      vaccination (DPV) using PCV2b. RESULTS: Both inactivated and live-attenuated
      chimeric PCV1-2b vaccines induced a robust antibody responses, and significantly
      decreased microscopic lesion and lower viral loads in serum or superficial
      inguinal lymph nodes (SILN) compared with that in the nonvaccinated challenged
      group. PCV2 antibody titers decreased after 7 days post challenge (DPC) in pigs
      administered the inactivated PCV1-2b vaccine and they were lower than those in
      pigs inoculated with live-attenuated PCV1-2b on the day of necropsy. Moreover, no
      viremia was present in pigs inoculated with live-attenuated PCV1-2b vaccine at 21
      DPC regardless of the dose difference. CONCLUSIONS: The results demonstrated that
      both inactivated and live-attenuated chimeric PCV1-2b vaccines were effective to
      induce protective immunity against PCV2b infection.

PMID- 26220292
TI  - An efficient microwave-assisted synthesis of cotinine and iso-cotinine analogs
      from an Ugi-4CR approach.
AB  - A convenient base-mediated two-step synthesis of cotinine analogs and a one-pot
      base-free synthesis of iso-cotinine derivatives featuring an Ugi-4CR/cyclization
      protocol are reported. These approaches exploit the reactivity of the peptidyl
      position present in the Ugi adducts, allowing the facile construction of the
      gamma-lactam core, as well as the introduction of a N-substituted methyl group
      into the analogs in a straightforward manner. A plausible mechanism for the
      cyclization step is discussed. 

PMID- 26220294
TI  - Retro-Brook Rearrangement of Ferrocene-Derived Silyl Ethers.
AB  - An intramolecular Li-Si exchange was observed on various lithiated
      ferrocenylbenzyl silyl ethers. The thermodynamically more stable C-silylated
      isomers were isolated in good yields and fully characterized. The reaction
      mechanism of the [1,4] retro-Brook rearrangement was investigated by DFT
      calculations. Two distinct reaction routes were proposed and a possible
      stabilization effect of the ferrocenyl fragment on the C-silylated isomers was
      described. The diastereoselective rearrangement of the trimethylsilyl group to
      the ortho position of the ferrocenyl cyclopentadienyl ring was also accomplished
      and the absolute configuration of the product was determined. 

PMID- 26220293
TI  - Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Severe traumatic injury and haemorrhagic shock are frequently
      associated with disruptions of coagulation function (such as trauma-induced
      coagulopathy TIC) and activation of inflammatory cascades. These pathologies may
      be exacerbated by current standard of care resuscitation protocols. Observational
      studies suggest early administration of plasma to severely-injured haemorrhaging
      patients may correct TIC, minimise inflammation, and improve survival. The
      proposed randomised clinical trial will evaluate the clinical effectiveness of
      pre-hospital plasma administration compared with standard- of-care crystalloid
      resuscitation in severely-injured patients with major traumatic haemorrhage.
      METHODS/DESIGN: This is a prospective, randomized, open-label, non-blinded trial
      to determine the effect of pre-hospital administration of thawed plasma (TP) on
      mortality, morbidity, transfusion requirements, coagulation, and inflammatory
      response in severely-injured bleeding trauma patients. Two hundred and ten
      eligible adult trauma patients will be randomised to receive either two units of
      plasma, to be administered in-field, vs standard of care normal saline (NS). Main
      analyses will compare subjects allocated to TP to those allocated to NS, on an
      intention-to-treat basis. Primary outcome measure is all-cause 30-day mortality.
      Secondary outcome measures include coagulation and lipidomic/pro-inflammatory
      marker responses, volume of resuscitation fluids (crystalloid, colloid) and blood
      products administered, and major hospital outcomes (e.g. incidence of MSOF,
      length of ICU stay, length of hospital stay). DISCUSSION: This study is part of a
      US Department of Defense (DoD)-funded multi-institutional investigation,
      conducted independently of, but in parallel with, the University of Pittsburgh
      and University of Denver. Demonstration of significant reductions in mortality
      and coagulopathic/inflammatory-related morbidities as a result of pre-hospital
      plasma administration would be of considerable clinical importance for the
      management of haemorrhagic shock in both civilian and military populations. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02303964 on 28 November 2014.

PMID- 26220295
TI  - Modeling leucine's metabolic pathway and knockout prediction improving the
      production of surfactin, a biosurfactant from Bacillus subtilis.
AB  - A Bacillus subtilis mutant strain overexpressing surfactin biosynthetic genes was
      previously constructed. In order to further increase the production of this
      biosurfactant, our hypothesis is that the surfactin precursors, especially
      leucine, must be overproduced. We present a three step approach for leucine
      overproduction directed by methods from computational biology. Firstly, we
      develop a new algorithm for gene knockout prediction based on abstract
      interpretation, which applies to a recent modeling language for reaction networks
      with partial kinetic information. Secondly, we model the leucine metabolic
      pathway as a reaction network in this language, and apply the knockout prediction
      algorithm with the target of leucine overproduction. Out of the 21 reactions
      corresponding to potential gene knockouts, the prediction algorithm selects 12
      reactions. Six knockouts were introduced in B. subtilis 168 derivatives strains
      to verify their effects on surfactin production. For all generated mutants, the
      specific surfactin production is increased from 1.6- to 20.9-fold during the
      exponential growth phase, depending on the medium composition. These results show
      the effectiveness of the knockout prediction approach based on formal models for
      metabolic reaction networks with partial kinetic information, and confirms our
      hypothesis that precursors supply is one of the main parameters to optimize
      surfactin overproduction. 

PMID- 26220296
TI  - Bordetella bronchialis sp. nov., Bordetella flabilis sp. nov. and Bordetella
      sputigena sp. nov., isolated from human respiratory specimens, and
      reclassification of Achromobacter sediminum Zhang et al. 2014 as Verticia
      sediminum gen. nov., comb. nov.
AB  - The phenotypic and genotypic characteristics of four Bordetella hinzii-like
      strains from human respiratory specimens and representing nrdA gene sequence
      based genogroups 3, 14 and 15 were examined. In a 16S rRNA gene sequence based
      phylogenetic tree, the four strains consistently formed a single coherent lineage
      but their assignment to the genus Bordetella was equivocal. The respiratory
      quinone, polar lipid and fatty acid profiles generally conformed to those of
      species of the genus Bordetella and were characterized by the presence of
      ubiquinone 8, of phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol and several aminolipids, and of high percentages of C16 :
      0, cyclo-C17 : 0 and summed feature 2, as major chemotaxonomic marker molecules,
      respectively. The DNA G+C content was about 66 mol%, which corresponded with that
      of the high-percentage DNA G+C content genera of the family Alcaligenaceae
      including the genus Bordetella. DNA-DNA hybridization experiments revealed the
      presence of three distinct genomospecies and thus confirmed phenotypic
      differences as revealed by means of extensive biochemical characterization. We
      therefore propose to formally classify Bordetella genogroups 3, 14 and 15 as
      Bordetella bronchialis sp. nov. (type strain LMG 28640T = AU3182T = CCUG 56828T),
      Bordetella sputigena sp. nov. (type strain LMG 28641T = CCUG 56478T) and
      Bordetella flabilis sp. nov. (type strain LMG 28642T = AU10664T = CCUG 56827T).
      In addition, we propose to reclassify Achromobacter sediminum into the novel
      genus Verticia, as Verticia sediminum, gen. nov., comb. nov., on the basis of its
      unique phylogenetic position, its marine origin and its distinctive phenotypic,
      fatty acid and polar lipid profile.

PMID- 26220299
TI  - Effects of scleral cross-linking using genipin on the process of form-deprivation
      myopia in the guinea pig: a randomized controlled experimental study.
AB  - BACKGROUND: Scleral cross-linking (CXL) is a novel attempt to slow down the axial
      elongation process in animal eyes. As a natural CXL reagent, genipin would be
      also effective for the prevention of myopia process. Thus, the present study was
      designed to evaluate the effects of scleral cross-linking using genipin on the
      form-deprivation (FD) myopia process of guinea pigs. METHODS: Twenty-seven 3-week
      old pigmented guinea pigs were randomly divided into three groups. Group A (n =
      8) is the untreated control group. Group B (n = 8) is the FD control group, where
      all eyes were induced with monocular FD for 21 days. In Group C (n = 11), a sub
      Tenon injection of 0.10 mL 0.50 % genipin was performed on FD eyes at day 0, 7
      and 14 during the 21-day monocular FD. The ocular refraction, axial length,
      biomechanical test and light and electron microscopy were measured on all eyes to
      check the efficacy and safety of this scleral CXL technique. RESULTS: Compared
      with Group A, significant increases in myopic refractive errors, axial elongation
      and reductions of scleral fibril diameter and density were observed in the 21-day
      FD eyes of Group B (P < 0.05). In Group C, the scleral CXL resulted in less
      myopia and axial elongation as compared with Group B (P < 0.05); a significant
      thickening of scleral fibrils was found after sub-Tenon injections of genipin; no
      histological damage on the retina or choroid was observed in Group C at the end
      of this study. CONCLUSIONS: The FD myopia in guinea pig eyes was effectively
      blocked by the scleral CXL using sub-Tenon injections of genipin. No histological
      damage was found on the retina or choroid of these treated eyes. Further studies
      are needed to examine the long-term efficacy and safety of this CXL technique.

PMID- 26220300
TI  - Sound quality in adult cochlear implant recipients using the HISQUI19.
AB  - CONCLUSION: On average, adult CI recipients report a moderate sound quality using
      the Dutch version of the HISQUI19 questionnaire. These results are correlated
      with their age, speech perception scores, CI aided hearing thresholds, and the
      SSQ5 and the APHAB questionnaire. BACKGROUND: The general aim of the study was to
      assess sound quality in adult cochlear implant (CI) recipients and to link these
      findings to other patients reported outcome measures (PROM) and subject
      characteristics. Therefore, the Hearing Implant Sound Quality Index (HISQUI19),
      which was translated into Dutch, was used. This user-friendly instrument
      quantifies sound quality experienced by hearing implant users. METHODS: The Dutch
      version of the original German HISQUI19 was obtained by the process of
      translation and back-translation. The HISQUI19 was assessed in 65 experienced
      adult CI users at the Ear, Nose, and Throat (ENT) department of the Antwerp
      University Hospital to assess a sound quality profile of experiences adult CI
      recipients. Therefore, descriptive statistics were used to summarize the mean,
      standard deviation, and ceiling or floor effects of the total HISQUI19 scores in
      a CI population. Spearman correlations between the HISQUI19 scores and objective
      audiological measures and other PROM were investigated (APHAB and SSQ5
      questionnaire). RESULTS: The mean HISQUI19 score of the Dutch version in adult CI
      recipients was 64.9 (SD = 20.8), which corresponds to moderate sound quality. The
      psychometric characters of the Dutch questionnaire are similar to the characters
      of the original HISQUI19 questionnaire, emphasizing good internal consistency
      (alpha = 0.93) and construct validity. Moderate correlation was found with speech
      perception in quiet (r = 0.36, p < 0.01), speech perception in noise (r = 0.29, p
      < 0.05), CI aided Pure Tone Average (PTA0.5, 1, 2 and 4 kHz) of the subjects (r =
      0.34, p < 0.01), and the age of the subject (r = 0.38, p < 0.01). Gender did not
      influence the experienced sound quality significantly. Furthermore, the relation
      to other questionnaires was found to be significantly strong (SSQ5: r = 0.68 and
      the APHAB: r = 0.64; p < 0.01).

PMID- 26220297
TI  - Transcriptional analysis of susceptible and resistant European corn borer strains
      and their response to Cry1F protoxin.
AB  - BACKGROUND: Despite a number of recent reports of insect resistance to transgenic
      crops expressing insecticidal toxins from Bacillus thuringiensis (Bt), little is
      known about the mechanism of resistance to these toxins. The purpose of this
      study is to identify genes associated with the mechanism of Cry1F toxin
      resistance in European corn borer (Ostrinia nubilalis Hubner). For this, we
      compared the global transcriptomic response of laboratory selected resistant and
      susceptible O. nubilalis strain to Cry1F toxin. We further identified
      constitutive transcriptional differences between the two strains. RESULTS: An O.
      nubilalis midgut transcriptome of 36,125 transcripts was assembled de novo from
      106 million Illumina HiSeq and Roche 454 reads and used as a reference for
      estimation of differential gene expression analysis. Evaluation of gene
      expression profiles of midgut tissues from the Cry1F susceptible and resistant
      strains after toxin exposure identified a suite of genes that responded to the
      toxin in the susceptible strain (n = 1,654), but almost 20-fold fewer in the
      resistant strain (n = 84). A total of 5,455 midgut transcripts showed significant
      constitutive expression differences between Cry1F susceptible and resistant
      strains. Transcripts coding for previously identified Cry toxin receptors,
      cadherin and alkaline phosphatase and proteases were also differentially
      expressed in the midgut of the susceptible and resistant strains. CONCLUSIONS:
      Our current study provides a valuable resource for further molecular
      characterization of Bt resistance and insect response to Cry1F toxin in O.
      nubilalis and other pest species.

PMID- 26220301
TI  - Global efforts in conquering lung cancer in China.
AB  - Lung cancer, the most prevalent and deadly malignancy in the world, poses a
      particularly critical healthcare challenge to China due to the rapidly increasing
      new cases and the unique cancer genetics in Chinese patient population.
      Substantial progress has been made in molecular diagnosis and personalized
      treatment of the disease. The field is now moving towards multiple new directions
      to include (1) new generation of targeted agents such as epidermal growth factor
      receptor and anaplastic lymphoma kinase inhibitors to overcome resistance to
      their early generation counterparts; and (2) deeper understanding of tumor
      genetics of each individual patient and consequently the application of
      biomarkers to guide personalized treatment as well as novel drug development
      including combination therapy. The increasing capacity in innovative cancer drug
      research and development is supported by extensive collaboration within China and
      globally, and across academia and industry, to build up expertise and
      infrastructure in early-phase clinical testing of novel drugs. With these
      combined efforts, new and better medicines will be available for lung cancer
      patients in China in the near future. 

PMID- 26220302
TI  - Performance of Nonmigratory Iron Chelating Active Packaging Materials in Viscous
      Model Food Systems.
AB  - Many packaged food products undergo quality deterioration due to iron promoted
      oxidative reactions. Recently, we have developed a nonmigratory iron chelating
      active packaging material that represents a novel approach to inhibit oxidation
      of foods while addressing consumer demands for "clean? labels. A challenge to the
      field of nonmigratory active packaging is ensuring that surface-immobilized
      active agents retain activity in a true food system despite diffusional
      limitations. Yet, the relationship between food viscosity and nonmigratory active
      packaging activity retention has never been characterized. The objective of this
      study was to investigate the influence of food viscosity on iron chelation by a
      nonmigratory iron chelating active packaging material. Methyl cellulose was added
      to aqueous buffered iron solutions to yield model systems with viscosities
      ranging from ~1 to ~10(5)  mPa.s, representing viscosities ranging from beverage
      to mayonnaise. Iron chelation was quantified by material-bound iron content using
      colorimetry and inductively coupled plasma-optical emission spectrometry (ICP
      OES).  Maximum iron chelation was reached in solutions up to viscosity ~10(2) 
      mPa.s. In more viscous solutions (up to ~10(4)  mPa.s), there was a significant
      decrease in iron chelating capacity (P < 0.05). However, materials still retained
      at least 76% iron chelating capacity. Additionally, the influence of different
      food hydrocolloids on the performance of nonmigratory iron chelating active
      packaging was characterized. Methyl cellulose and carrageenan did not compete
      with the material for specific iron chelation (P > 0.05). Materials retained 32%
      to 45% chelating capacity when in contact with competitively chelating
      hydrocolloids guar gum, locust bean gum, and xanthan gum. This work demonstrates
      the potential application of nonmigratory iron chelating active packaging in
      liquid and semi-liquid foods to allow for the removal of synthetic chelators,
      while maintaining food quality. 

PMID- 26220303
TI  - Advanced continuous cultivation methods for systems microbiology.
AB  - Increasing the throughput of systems biology-based experimental characterization
      of in silico-designed strains has great potential for accelerating the
      development of cell factories. For this, analysis of metabolism in the steady
      state is essential as only this enables the unequivocal definition of the
      physiological state of cells, which is needed for the complete description and in
      silico reconstruction of their phenotypes. In this review, we show that for a
      systems microbiology approach, high-resolution characterization of metabolism in
      the steady state--growth space analysis (GSA)--can be achieved by using advanced
      continuous cultivation methods termed changestats. In changestats, an
      environmental parameter is continuously changed at a constant rate within one
      experiment whilst maintaining cells in the physiological steady state similar to
      chemostats. This increases the resolution and throughput of GSA compared with
      chemostats, and, moreover, enables following of the dynamics of metabolism and
      detection of metabolic switch-points and optimal growth conditions. We also
      describe the concept, challenge and necessary criteria of the systematic analysis
      of steady-state metabolism. Finally, we propose that such systematic
      characterization of the steady-state growth space of cells using changestats has
      value not only for fundamental studies of metabolism, but also for systems
      biology-based metabolic engineering of cell factories.

PMID- 26220304
TI  - Hypolipidemic influence of dietary fenugreek (Trigonella foenum-graecum) seeds
      and garlic (Allium sativum) in experimental myocardial infarction.
AB  - The cardioprotective influence of dietary fibre-rich fenugreek seeds and the well
      established hypolipidemic spice garlic was evaluated both individually and in
      combination in isoproterenol induced myocardial infarcted rats. It was
      particularly examined whether pretreatment with dietary fenugreek, garlic or
      fenugreek + garlic would be beneficial under hypercholesterolemic conditions by
      their influence on the tissue lipid profile. Four groups each of male Wistar rats
      were maintained on either a basal diet or a high cholesterol diet for 8 weeks.
      Dietary interventions with fenugreek, garlic and the combination of fenugreek and
      garlic were made by including 10% fenugreek seed powder, 2% freeze-dried garlic
      powder, and 10% fenugreek seed powder + 2% garlic powder. At the end of the diet
      regimen, myocardial infarction was induced with isoproterenol (i.p. 80 mg kg(-1))
      twice at intervals of 12 h. The disturbed activities of cardiac marker enzymes in
      serum and the heart confirmed isoproterenol induced myocardial infarction.
      Dietary fenugreek, garlic or fenugreek + garlic was found to ameliorate the
      pathological changes in heart tissue and lipid abnormalities in serum and the
      heart, the beneficial effect being higher with the combination of fenugreek and
      garlic, invariably amounting to an additive effect. The results also indicated
      that the hypercholesterolemic situation aggravated the myocardial damage during
      isoproterenol-induced myocardial infarction. This dietary intervention study
      suggested that the combination of fenugreek seeds and garlic offers a higher
      beneficial influence in exerting the cardioprotective effect. 

PMID- 26220305
TI  - Epidemiology of human influenza A(H7N9) infection in Hong Kong.
AB  - BACKGROUND/PURPOSE: We conducted a case series study to review the epidemiology
      of human influenza A(H7N9) infection reported in Hong Kong. METHODS: We reviewed
      case records of confirmed human cases of influenza A(H7N9) infection reported in
      Hong Kong in the 2013-2014 winter season. We compared the median viral shedding
      duration and interval from illness onset to initiation of oseltamivir treatment
      between severe and mild cases. We estimated the incubation period of influenza
      A(H7N9) virus from cases with a single known date of poultry exposure. RESULTS: A
      total of 10 cases were reported and all were imported infection from Mainland
      China. Four patients died and the cause of death was related to influenza A(H7N9)
      infection in two patients. The median interval from illness onset to initiation
      of oseltamivir treatment for the severe cases (4.5 days) was significantly longer
      than the mild cases (2 days; p = 0.025). Severe cases had a significantly longer
      viral shedding duration than mild cases (p = 0.028). The median incubation period
      for cases with a single known exposure date was 4 days. Nasopharyngeal aspirate
      taken from the 88 close contacts of the 10 patients all tested negative for
      influenza A virus using reverse transcription polymerase chain reaction.
      CONCLUSION: Delayed administration of antiviral treatment may be associated with
      a more severe illness for influenza A(H7N9) infection. Despite our aggressive
      contact tracing policy with laboratory testing of all close contacts, no
      secondary case was identified which implied that the potential of human-to-human
      transmission of the circulating influenza A(H7N9) virus remains low.

PMID- 26220306
TI  - Changes from 1986 to 2006 in reasons for liking leisure-time physical activity
      among adolescents.
AB  - Reasons for participating in physical activity (PA) may have changed in
      accordance with the general modernization of society. The aim is to examine
      changes in self-reported reasons for liking leisure-time physical activity (LTPA)
      and their association with self-reported LTPA over a 20-year period. Data were
      collected among nationally representative samples of 13-year-olds in Finland,
      Norway, and Wales in 1986 and 2006 (N = 9252) as part of the WHO cross-national
      Health Behaviour in School-aged Children (HBSC) study. Univariate ANOVAs to
      establish differences according to gender, year, and country were conducted. In
      all countries, 13-year-olds in 2006 tended to report higher importance in terms
      of achievement and social reasons than their counterparts in 1986, while changes
      in health reasons were minor. These reasons were associated with LTPA in a
      similar way at both time points. Health reasons for liking LTPA were considered
      most important, and were the strongest predictor of LTPA. The findings seem
      robust as they were consistent across countries and genders. Health education
      constitutes the most viable strategy for promoting adolescents' motivation for
      PA, and interventions and educational efforts could be improved by an increased
      focus on LTPA and sport as a social activity. 

PMID- 26220307
TI  - Monitoring the intramolecular charge transfer process in the Z907 solar cell
      sensitizer: a transient Vis and IR spectroscopy and ab initio investigation.
AB  - We have analyzed the excited state dynamics of the heteroleptic [(NCS)2Ru(bpy
      (COOH)2)(bpy-(C6H13)2)] Z907 solar cell sensitizer in solution and when adsorbed
      onto thin TiO2 films, by combining transient visible and infrared (IR)
      spectroscopies with ab initio Density Functional Theory (DFT) and Time-Dependent
      DFT (TDDFT) calculations. Upon excitation with ultra-short pulses in ethanol and
      dimethyl-sulphoxide solutions, the visible spectra show the appearance of a
      positive signal around 650 nm, within the instrumental time resolution (<100 fs),
      which in ethanol undergoes a red-shift in about 20 ps. Measurements in the IR
      indicate that, upon excitation, both the CN and CO marker bands, associated with
      the NCS and COOH groups, downshift in frequency, in response to intramolecular
      ligand + metal (Ru-NCS) to ligand' (bpy-COOH2) charge transfer (LML'CT).
      Vibrational cooling is observed in both solvents; in ethanol it is overtaken by
      the hydrogen bond dynamics. On the basis of DFT/TDDFT calculations, explicitly
      modeling the interaction of the NCS and COOH groups with solvent (ethanol)
      molecules, we rationalize the observed IR and visible spectral evolution as
      arising from the change in the hydrogen-bond network, which accompanies the
      transition to the lowest-energy triplet state. This interpretation provides a
      consistent explanation of what is also observed in the transient visible spectra.
      Transient IR measurements repeated for molecules adsorbed on TiO2 and ZrO2 films,
      allow us to identify the structural changes signaling the dye triplet excited
      state formation and evidence multiexponential electron injection rates into the
      semiconductor TiO2 film. 

PMID- 26220308
TI  - Are Children the Better Placebo Analgesia Responders? An Experimental Approach.
AB  - There is little information regarding changes in placebo responsiveness with age,
      although first predictors of placebo responders such as psychological and
      physiological processes have been identified. Reviews and meta-analyses indicate
      that placebo response rates in randomized controlled trials (RCTs) are higher in
      children and adolescents compared with adults. As these studies cannot control
      for age-dependent differences in the natural course of the disease, biases might
      contribute to different placebo rates in RCTs. To avoid these biases, this study
      investigated age-related differences in placebo responsiveness between children
      and adults in a well-established experimental model of placebo analgesia
      combining classic conditioning and expectation. Our data confirm placebo
      analgesic responses in children, which did not differ in magnitude from those of
      adults. The influence of previous experience on subsequent treatment outcome was
      stronger in children than in adults, indicating an increased relevance of
      learning processes for treatment outcomes in children. Further studies are needed
      to understand the influence of treatment-related learning processes in children
      and adolescents, which might critically determine treatment responsiveness during
      adulthood. PERSPECTIVE: This study is the first to experimentally explore placebo
      analgesia and influences of previous experience on placebo responses in children
      compared with adults. We found comparable placebo responses in both groups and an
      increased relevance of learning processes for treatment outcomes in children.

PMID- 26220309
TI  - Elevated CO2 induces a bloom of microphytobenthos within a shell gravel mesocosm.
AB  - The geological storage of carbon dioxide (CO2) is expected to be an important
      component of future global carbon emission mitigation, but there is a need to
      understand the impacts of a CO2 leak on the marine environment and to develop
      monitoring protocols for leakage detection. In the present study, sediment cores
      were exposed to CO2-acidified seawater at one of five pH levels (8.0, 7.5, 7.0,
      6.5 and 6.0) for 10 weeks. A bloom of Spirulina sp. and diatoms appeared on
      sediment surface exposed to pH 7.0 and 7.5 seawater. Quantitative PCR
      measurements of the abundance of 16S rRNA also indicated an increase within the
      pH 7.0 and 7.5 treatments after 10 weeks incubation. More detailed analysis of
      the microbial communities from the pH 7.0, 7.5 and 8.0 treatments confirmed an
      increase in the relative abundance of Spirulina sp. and Navicula sp. sequences,
      with changes in the relative abundance of major archaeal and bacterial groups
      also detected within the pH 7.0 treatment. A decreased flux of silicate from the
      sediment at this pH was also detected. Monitoring blooms of microphytobenthos may
      prove useful as an indicator of CO2 leakage within coastal areas. 

PMID- 26220310
TI  - Microform-related community patterns of methane-cycling microbes in boreal
      Sphagnum bogs are site specific.
AB  - Vegetation and water table are important regulators of methane emission in
      peatlands. Microform variation encompasses these factors in small-scale
      topographic gradients of dry hummocks, intermediate lawns and wet hollows. We
      examined methane production and oxidization among microforms in four boreal bogs
      that showed more variation of vegetation within a bog with microform than between
      the bogs. Potential methane production was low and differed among bogs but not
      consistently with microform. Methane oxidation followed water table position with
      microform, showing higher rates closer to surface in lawns and hollows than in
      hummocks. Methanogen community, analysed by mcrA terminal restriction fragment
      length polymorphism and dominated by Methanoregulaceae or 'Methanoflorentaceae',
      varied strongly with bog. The extent of microform-related variation of
      methanogens depended on the bog. Methanotrophs identified as Methylocystis spp.
      in pmoA denaturing gradient gel electrophoresis similarly showed effect of bog,
      and microform patterns were stronger within individual bogs. Our results suggest
      that methane-cycling microbes in boreal Sphagnum bogs with seemingly uniform
      environmental conditions may show strong site-dependent variation. The bog
      intrinsic factor may be related to carbon availability but contrary to
      expectations appears to be unrelated to current surface vegetation, calling
      attention to the origin of carbon substrates for microbes in bogs. 

PMID- 26220311
TI  - Complete genome sequence of Piscirickettsia salmonis LF-89 (ATCC VR-1361) a major
      pathogen of farmed salmonid fish.
AB  - Piscirickettsia salmonis, the causative agent of salmonid rickettsial septicemia
      (SRS), is a significant threat to the healthy and sustainable production of
      salmonid farming industry. This Gram-negative bacterium, originally isolated from
      a coho salmon in Southern Chile, produces a systemic infection characterized by
      colonization of several fish organs. P. salmonis is able to infect, survive, and
      replicate inside salmonid macrophages however little is known about its
      mechanisms of pathogenesis. Here, we present the whole genome sequence and
      annotation of the P. salmonis reference strain LF-89 (ATCC VR-1361). The genome
      contains one circular chromosome of 3,184,851 bp and three plasmids, pPSLF89-1
      (180,124 bp), pPSLF89-2 (33,516 bp) and pPSLF89-3 (51,573 bp). A total of 2850
      protein-coding genes, 56 tRNAs and six copies of 5S-16S-23S rRNA.

PMID- 26220312
TI  - High affinity receptor labeling based on basic leucine zipper domain peptides
      conjugated with pH-sensitive fluorescent dye: Visualization of AMPA-type
      glutamate receptor endocytosis in living neurons.
AB  - Techniques to visualize receptor trafficking in living neurons are important, but
      currently available methods are limited in their labeling efficiency, specificity
      and reliability. Here we report a method for receptor labeling with a basic
      leucine zipper domain peptide (ZIP) and a binding cassette specific to ZIP.
      Receptors are tagged with a ZIP-binding cassette at their extracellular domain.
      Tagged receptors expressed in cultured cells were labeled with exogenously
      applied fluorescently labeled ZIP with low background and high affinity. To test
      if ZIP labeling is useful in monitoring endocytosis and intracellular
      trafficking, we next conjugated ZIP with a pH-sensitive dye RhP-M (ZIP-RhP-M).
      ZIP binding to its binding cassette was pH-resistant and RhP-M fluorescence
      dramatically increased in acidic environment. Thus AMPA-type glutamate receptors
      (AMPARs) labeled by ZIP-RhP-M can report receptor endocytosis and subsequent
      intracellular trafficking. Application of ZIP-RhP-M to cultured hippocampal
      neurons expressing AMPARs tagged with a ZIP-binding cassette resulted in
      appearance of fluorescent puncta in PSD-95-positive large spines, suggesting
      local endocytosis and acidification of AMPARs in individual mature spines. This
      spine pool of AMPARs in acidic environment was distinct from the early endosomes
      labeled by transferrin uptake. These results suggest that receptor labeling by
      ZIP-RhP-M is a useful technique for monitoring endocytosis and intracellular
      trafficking. This article is part of the Special Issue entitled 'Synaptopathy-
      from Biology to Therapy'.

PMID- 26220313
TI  - Cotransmission of acetylcholine and GABA.
AB  - Neurons that produce acetylcholine (ACh) are positioned to broadly influence the
      brain, with axonal arborizations that extend throughout the cerebral cortex,
      striatum, and hippocampus. While the action of these neurons has typically been
      attributed entirely to ACh, neurons often release more than one primary
      neurotransmitter. Here, we review evidence for the cotransmission of the
      inhibitory neurotransmitter GABA from cholinergic neurons throughout the
      mammalian central nervous system. Functional cotransmission of ACh and GABA has
      been reported in the retina and cortex, and anatomical studies suggest that GABA
      cotransmission is a common feature of nearly all forebrain ACh-producing neurons.
      Further experiments are necessary to confirm the extent of GABA cotransmission
      from cholinergic neurons, and the contribution of GABA needs to be considered
      when studying the functional impact of activity in ACh-producing neurons. This
      article is part of the Special Issue entitled 'Synaptopathy--from Biology to
      Therapy'.

PMID- 26220314
TI  - A single polycystic kidney disease 2-like 1 channel opening acts as a spike
      generator in cerebrospinal fluid-contacting neurons of adult mouse brainstem.
AB  - Cerebrospinal fluid contacting neurons (CSF-cNs) are found around the central
      canal of all vertebrates. They present a typical morphology, with a single
      dendrite that projects into the cavity and ends in the CSF with a protuberance.
      These anatomical features have led to the suggestion that CSF-cNs might have
      sensory functions, either by sensing CSF movement or composition, but the
      physiological mechanisms for any such role are unknown. This hypothesis was
      recently supported by the demonstration that in several vertebrate species
      medullo-spinal CSF-cNs selectively express Polycystic Kidney Disease 2-Like 1
      proteins (PKD2L1). PKD2L1 are members of the 'transient receptor potential (TRP)'
      superfamily, form non-selective cationic channels of high conductance, are
      regulated by various stimuli including protons and are therefore suggested to act
      as sensory receptors. Using patch-clamp whole-cell recordings of CSF-cNs in
      brainstem slices obtained from wild type and mutant PKD2L1 mice, we demonstrate
      that spontaneously active unitary currents in CSF-cNs are due to PKD2L1 channels
      that are capable, with a single opening, of triggering action potentials. Thus
      PKD2L1 might contribute to the setting of CSF-cN spiking activity. We also reveal
      that CSF-cNs have the capacity of discriminating between alkalinization and
      acidification following activation of specific conductances (PKD2L1 vs. ASIC)
      generating specific responses. Altogether, this study reinforces the idea that
      CSF-cNs represent sensory neurons intrinsic to the central nervous system and
      suggests a role for PKD2L1 channels as spike generators. 

PMID- 26220317
TI  - Canine neural angiostrongylosis: a case-control study in Sydney dogs.
AB  - The editors wish to correct an error in the Results section. On page 197, third
      paragraph, lines 3-5 should read: Younger dogs were significantly (P<0.001) more
      likely to be cases than older dogs (odds ratio 11.8; 95% confidence interval 3.9
      35.9). The editors sincerely apologise for this error.

PMID- 26220315
TI  - Effectiveness of psychological support in patients undergoing primary total hip
      or knee arthroplasty: a controlled cohort study.
AB  - BACKGROUND: We hypothesised that psychological support would have a significant
      improvement on the mental and physical recovery of patients undergoing primary
      total hip or knee arthroplasty. MATERIALS AND METHODS: 200 patients were
      consecutively alternately assigned (1:1) to receive routine care (control group)
      or, in addition, psychological support from a professional psychologist
      (experimental group). The psychological support was provided at the pre-operative
      visit, during the hospitalisation period and at the rehabilitation centre.
      RESULTS: Upon discharge, based on the 'Hospital Anxiety and Depression Scale, a
      state of anxiety was observed in 12.8 % and 78.9 % of the patients in the
      experimental and in the control group, respectively (p < 0.0001). A state of
      depression was observed in 12.8 % and 73.7 % of the patients in the experimental
      and in the control group, respectively (p < 0.0001). With regard to the 'Physical
      Component Scale' of the SF-36 questionnaire, a similar temporal trend of values
      was observed in the two study groups, significantly increasing over time in both
      groups, taking into consideration both the joint population and the two hip and
      knee populations separately (p < 0.0001). With regard to the 'Mental Component
      Scale' of the SF-36 questionnaire, in both the joint population and the two hip
      and knee populations separately, an exact opposite temporal trend was observed in
      the experimental group compared to the control group (p < 0.0001), with generally
      higher scores in the experimental group (p < 0.0001). In patients with hip
      arthroplasty, the average time to reach the physiotherapy objective (i.e., the
      patient ability to walk 50 metres independently and to climb 10 steps) was 6.7 +/
      1.8 days (range 4-12) in the experimental group and 7.9 +/- 2.2 days (range 0
      13) in the control group (p = 0.0015). CONCLUSIONS: In summary, there was a lower
      incidence of anxiety and depression and better mental well-being in the group of
      patients who received the psychological support. Within the hip arthroplasty
      group, the patients who received the psychological support reached the
      physiotherapy objective 1.2 days earlier than the patients in the control group
      (p = 0.0015). LEVEL OF EVIDENCE: Level 3, Non-randomized prospective controlled
      cohort.

PMID- 26220318
TI  - Randomised trial of the bioavailability and efficacy of orally administered
      flunixin, carprofen and ketoprofen in a pain model in sheep.
AB  - OBJECTIVE: To determine the efficacy and bioavailability of non-steroidal anti
      inflammatory drugs (NSAIDs) when administered orally to sheep. DESIGN: Randomised
      experimental design with four treatment groups: three NSAID groups and one
      control group (n = 10/group). The study animals were 40 18-month-old Merino ewes
      with an average weight of 31.4 +/- 0.5 kg. METHODS: Treatment was given orally at
      24 h intervals for 6 days at dose rates expected to achieve therapeutic levels in
      sheep: carprofen (8.0 mg/kg), ketoprofen (8.0 mg/kg) and flunixin (4.0 mg/kg).
      Oil of turpentine (0.1 mL) was injected into a forelimb of each sheep to induce
      inflammation and pain; responses (force plate pressure, skin temperature, limb
      circumference, haematology and plasma cortisol) were measured at 0, 3, 6, 9, 12,
      24, 36, 48, 72 and 96 h post-injection. NSAID concentrations were determined by
      ultra-high-pressure liquid chromatography. RESULTS: The NSAIDs were detectable in
      ovine plasma 2 h after oral administration, with average concentrations of 4.5
      8.4 ug/mL for ketoprofen, 2.6-4.1 ug/mL for flunixin and 30-80 ug/mL for
      carprofen. NSAID concentrations dropped 24 h after administration. Pain response
      to an oil of turpentine injection was assessed using the measures applied but no
      effect of the NSAIDs was observed. Although this pain model has been previously
      validated, the responses observed in this study differed from those in the
      previous study. CONCLUSIONS AND CLINICAL RELEVANCE: The three NSAIDs reached
      inferred therapeutic concentrations in blood at 2 h after oral administration.
      The oil of turpentine lameness model may need further validation.

PMID- 26220319
TI  - Effect of local infusion of NSAID analgesics administered alone or in combination
      on the pain associated with band castration in calves.
AB  - OBJECTIVE: To evaluate the analgesic efficacy of flunixin alone or in combination
      with diclofenac administered locally to the scrotum at the time of band
      castration of calves. METHODS: Angus bull calves (n = 40; ~7-9 weeks old) were
      allocated to four treatment groups (n = 10 per group) to examine the effects of
      two non-steroidal anti-inflammatory analgesics (NSAIDs) administered locally at
      the time of band castration: sham control; castration + flunixin; castration +
      flunixin + diclofenac; castration + saline. The NSAIDs and saline were
      administered subcutaneously into the scrotum under the band. Blood was sampled at
      -0.5, 0.5, 1.5, 3, 12, 24, 48 and 72 h relative to castration. Haematology
      parameters and plasma cortisol levels were determined in samples at all time
      points and plasma haptoglobin levels determined in samples collected at -0.5, 24,
      48 and 72 h. Pain avoidance and postural behaviours were measured for 2 and 12 h,
      respectively, after castration. RESULTS: Band-castrated calves exhibited
      significantly higher peak cortisol and higher integrated cortisol responses
      during the first 6 h post-castration relative to sham controls. Individual active
      pain avoidance behaviours observed for 1 h post-castration were not significantly
      different between treatment groups; however; the sum of the total behaviours was
      significantly increased by castration (P = 0.023). Postural changes included
      increased abnormal ventral lying for all castrated groups and decreased normal
      standing and increased combined abnormal postures for the flunixin- and saline
      treated groups. Growth rates of calves were not affected by treatments during
      weeks 1 and 2 post-castration; however, growth rates of castrated calves were
      significantly lower than those of sham-treated calves in week 3 post-castration
      (1.41 vs 0.84, 0.75 and 0.56+/-0.19 kg/day for sham, flunixin-, flunixin +
      diclofenac- and saline-treated groups, respectively). CONCLUSIONS: The
      administration of flunixin or flunixin + diclofenac intrascrotally at several
      sites at the time of banding did not improve the welfare of young Angus bull
      calves undergoing this method of castration when assessed by both physiological
      and behavioural parameters. In this study, band castration at 7-9 weeks of age
      had less effect compared with results for older calves reported previously.
      Further research is required to develop effective analgesic treatments that can
      be administered at the time of castration to large numbers of animals.

PMID- 26220320
TI  - Typing of Staphylococcus aureus isolated from bovine mastitis cases in Australia
      and India.
AB  - OBJECTIVE: To determine the prevalence of the different capsular polysaccharide
      (CP) and major surface-associated non-CP antigen 336 (SP-336) types among
      Staphylococcus aureus isolated from bovine mastitis cases in Australia and India.
      METHODS: A total of 414 strains (154 from Australia, 260 from India) isolated
      from clinical bovine mastitis were included in the study. Mouse antisera raised
      against CP types (CP1, CP2, CP5, and CP8) or SP-336 were used in slide
      agglutination tests and compared with detection of cap1, cap5 and cap8 gene
      fragments by PCR. RESULTS: Serological studies revealed the presence of CP2, CP5,
      CP8 and SP-336 in 9.1%, 23.4%, 31.8%, and 5.8% of the Australian versus 0.8%,
      46.9%, 13.1% and 0% of the Indian isolates, respectively. By PCR, CP1, CP5 and
      CP8 accounted for 0%, 26.6% and 32.4% of the Australian versus 3.9%, 85% and 8.1%
      of the Indian isolates, respectively. CONCLUSIONS: Both PCR and the serological
      method demonstrated that CP5 and CP8 are the predominant capsular types in
      Australia, whereas CP5 is the predominant capsular type in India. The study also
      demonstrated a strong correlation between both methods of typing for CP1, CP5,
      CP8 and non-typeable S. aureus strains. High-percentage prevalence of non
      typeable isolates in both the countries highlights the importance of continued
      investigations of the identification of unique surface-associated polysaccharide
      antigens prevalent among S. aureus isolates for the formulation of CP- and SP
      based vaccines for bovine mastitis.

PMID- 26220321
TI  - Axonal Spheroid Accumulation In the Brainstem and Spinal Cord of A Young Angus
      Cow with Ataxia.
AB  - CASE REPORT: An 18-month-old Angus cow presented with rapidly developing ataxia
      and subsequently died. The finding of large numbers of axonal spheroids in
      brainstem nuclei and spinal cord grey matter, bilaterally symmetrical in
      distribution, was consistent with a histopathological diagnosis of neuroaxonal
      dystrophy (NAD). Most of the axonal swellings were immunopositive to amyloid
      precursor protein, suggesting that interruption to axonal flow was important in
      their genesis. CONCLUSIONS: The topographical distribution of axonal spheroids in
      the brain and spinal cord in this bovine case closely resembled that found in the
      ovine neurodegenerative disorder termed NAD, in which axonal swellings are the
      major pathological feature. This appears to be the first reported case of this
      type of NAD in cattle. The aetiology of the spheroidal aggregations in this case
      was not determined. There was no evidence from the case history or neuropathology
      to indicate whether the axonal spheroids in this case involved an acquired or
      heritable aetiology.

PMID- 26220322
TI  - Survey of captive parrot populations around Port Phillip Bay, Victoria,
      Australia, for psittacine beak and feather disease virus, avian polyomavirus and
      psittacine adenovirus.
AB  - OBJECTIVE: This study investigated the prevalence of psittacine beak and feather
      disease virus (BFDV), avian polyomavirus (APV) and psittacine adenovirus (PsAdV)
      in captive psittacine birds around Port Phillip Bay, Victoria, Australia.
      METHODS: Samples of fresh droppings were collected from 118 psittacine birds (109
      clinically normal and 9 with feather abnormalities) from 11 avaries in different
      locations and were used for detection of BFDV, APV and PsAdV using PCR. RESULTS:
      BFDV, APV and PsAdV were detected in 31%, 13% and 4%, respectively, of the
      specimens tested. One budgerigar was found to be co-infected with BFDV and PsAdV.
      At least one sample tested positive for BFDV at each location. CONCLUSION: This
      is the first report of the prevalence of BFDV, APV and PsAdV in Victoria and
      provides a foundation for future studies examining the influence of these viruses
      on the health of aviary birds in Victoria.

PMID- 26220323
TI  - Flea (Ctenocephalides felis) control efficacy of topical indoxacarb on dogs
      subsequently bathed with a chlorhexidine-ketoconazole shampoo.
AB  - OBJECTIVE: An evaluation of the effect of chlorhexidine/ketoconazole shampoo
      baths on the flea control efficacy of indoxacarb applied topically to dogs.
      METHODS AND RESULTS: We randomly allocated 18 healthy mixed-breed dogs to 3
      groups: shampoo only; indoxacarb treated and medicated shampoo; and indoxacarb
      treated but not shampooed. Indoxacarb was administered on day 0 and dogs were
      shampooed on days 9 and 23. Dogs were infested with 100 adult Ctenocephalides
      felis initially 2 days before treatment and then weekly from days 7 to 28. Fleas
      were removed and counted 48 h post-infestation. CONCLUSION: Medicated shampoo use
      did not significantly reduce indoxacarb efficacy against C. felis.

PMID- 26220324
TI  - Mortality in northern corroboree frog tadpoles (Pseudophryne pengilleyi)
      associated with Tetrahymena-like infection.
AB  - CASE REPORT: Mortality of northern corroboree frog tadpoles and eggs occurred in
      association with Tetrahymena-like ciliates. The predominant lesions in the
      tadpoles were inflammation and necrosis of the dermis and skeletal muscle. Some
      of the egg capsules also contained ciliates, but were overgrown with bacteria and
      fungi. CONCLUSION: Disease occurred, secondary to underlying husbandry issues,
      and resolved following their correction.

PMID- 26220325
TI  - Rod the vet.

PMID- 26220326
TI  - An evaluator-blinded randomized controlled trial evaluating therapy effects and
      prognostic factors for a general and an individually defined physical therapy
      program in ambulant children with bilateral spastic cerebral palsy.
AB  - BACKGROUND: Cerebral palsy (CP) is characterized by a heterogeneous nature with a
      variety of problems. Therefore, individualized physical therapy might be more
      appropriate to address the needs for these children. AIM: The first aim was to
      compare the effectiveness of an individually-defined therapy program (IT) and a
      general therapy program (GT) on gait and gross motor function in children with
      CP. The second aim was to evaluate interaction-effects, time-effects, treatment
      with botulinum toxin A, age, gross Motor Function Classification Scale (GMFCS),
      treatment frequency and quality as factors influencing outcome. DESIGN: An
      evaluator-blinded, randomized controlled trial. SETTING: Outpatient
      rehabilitation unit. POPULATION: Forty ambulant children with spastic bilateral
      CP (mean age 6 years 1 month). METHODS: All children were randomly assigned to
      receive either IT or GT over a 10 week period. Nineteen of these children were
      enrolled into a second and/or third program, resulting in 60 interventions.
      Primary outcome was assessed with the Goal Attainment Scale (GAS) for gross motor
      function goals and z-scores for goals based on specific 3D gait parameters.
      Secondary outcome included the Gross Motor Function Measure-88 (GMFM-88) scores,
      time and distance gait parameters, Gait Profile Score, Movement Analysis Profiles
      and time needed to complete Timed-Up-and-Go and Five-Times-Sit-To-Stand tests.
      RESULTS: There were higher, but non-significant GAS and z-score changes following
      the IT program compared to the GT program (GAS: 46.2 for the IT versus 42.2 for
      the GT group, P=0.332, ES 0.15; z-score: 0.135 for the IT compared to 0.072 for
      the GT group, P=0.669, ES 0.05). Significant time-effects could be found on the
      GAS (P<0.001) and the GMFM-88 total score (P<0.001). Age was identified as a
      predictor for GAS and GMFM-88 improvement (P=0.023 and P=0.044). CONCLUSION: No
      significant differences could be registered between the effects of the IT and the
      GT. The favorable outcome after the IT program was only a trend and needs to be
      confirmed on larger groups and with programs of longer duration. CLINICAL
      REHABILITATION IMPACT: Both programs had a positive impact on the children's
      motor functioning. It is useful to involve older children more actively in the
      process of goal setting.

PMID- 26220327
TI  - Early versus delayed rehabilitation treatment in hemiplegic patients with
      ischemic stroke: proprioceptive or cognitive approach?
AB  - BACKGROUND: Early/intensive mobilization may improve functional recovery after
      stroke but it is not clear which kind of "mobilization" is more effective.
      Proprioceptive neuromuscular facilitation (PNF) and cognitive therapeutic
      exercise (CTE) are widespread applied in post-stroke rehabilitation but their
      efficacy and safety have not been systematically investigated. AIM: To compare
      PNF and CTE methods in a two different time setting (early versus standard
      approach) in order to evaluate different role of time and techniques in
      functional recovery after acute ischemic stroke. DESIGN: We designed a
      prospectical multicenter blinded interventional study of early versus standard
      approach with two different methods by means of both PNF and CTE. SETTING: A
      discrete stroke-dedicated area for out-of-thrombolysis patients, connected with
      two different comprehensive stroke centres in two different catchment areas.
      POPULATION: Three hundred and forty consecutive stroke patient with first ever
      sub-cortical ischemic stroke in the mean cerebral artery (MCA) territory and
      contralateral hemiplegia admitted within 6 and 24 hours from symptoms onset.
      METHODS: All patients were randomly assigned by means of a computer generated
      randomization sequence in blocks of 4 to one to the 4 interventional groups:
      early versus delayed rehabilitation programs with Kabat's schemes or Perfetti's
      technique. Patients in both delayed group underwent to a standard protocol in the
      acute phase. PRIMARY OUTCOME: disability at 3-12 months. Disability measures:
      modified Rankin Score and Barthel Index. Safety outcome: immobility-related
      adverse events. SECONDARY OUTCOME MEASURES: Six-Minute Walking Test, Motricity
      Index, Mini-Mental State Examination, Beck Depression Inventory. RESULTS:
      Disability was not different between groups at 3 months but Barthel Index
      significantly changed between early versus delayed groups at 12 months (P=0.01).
      Six-Minute Walking Test (P=0.01) and Motricity Index in both upper (P=0.01) and
      lower limbs (P=0.001) increased in early versus delayed groups regardless
      rehabilitation schedule. CONCLUSIONS: A time-dependent effect of rehabilitation
      on post stroke motor recovery was observed, particularly in lower limb
      improvement. According to our results, rehabilitation technique seems not to
      affect long term motor recovery. CLINICAL REHABILITATION IMPACT: These results
      show a significant effect of time but not of technique that may impact the
      decision making in the acute phase of care.

PMID- 26220328
TI  - Oxygen saturation and heart rate monitoring during a single session of early
      rehabilitation after cardiac surgery.
AB  - BACKGROUND: Early rehabilitation after cardiac surgery aims to prevent
      immobilization, to reduce the effects of surgery on the respiratory function and
      to facilitate the recovery of autonomy in the activities of daily living (ADL),
      after discharge. Nevertheless the optimal perioperative physical therapy care for
      patients undergoing cardiac surgery is not well established. Moreover, most of
      the studies monitored peripheral oxygen saturation (SpO2) and heart rate (HR)
      during surgery or focused only on their recovery after rehabilitation and not on
      their pathways during a session of exercises. AIM: To monitor peripheral oxygen
      saturation and HR before, during and at the end of a single session of early
      rehabilitation after cardiac surgery, so testing our protocol's safety. DESIGN: A
      case series. SETTING: Department of Cardiothoracic Surgery, inpatients.
      POPULATION: Forty-eight consecutive inpatients (35 M), mean age 61 years, with
      cardiovascular disease (CVD), who underwent cardiac surgery. METHODS: We
      monitored SpO2%, HR, systemic blood pressure (BP), pain in the thoracic wound
      (VAS) and rate of perceived exertion (RPE) during the rehabilitation session
      after weaning from oxygen therapy. RESULTS: During all phases mean SpO2 was 94%
      (+/-1.8) and mean HR was 85 bpm (+/-13.3). Number of desaturation events were 14
      in total and mean of % of time with SpO2<90% was 3 (+/-6.5) during all the
      rehabilitative session. Moreover, mean BP after reaching the sitting position was
      124.7 (+/-11.9)/78.6 (+/-8.4) and after ambulation was 131.5 (+/-11.5)/82.9 (+/
      7.3). CONCLUSION: The monitoring peripheral oxygen saturation and HR during and
      not only before and at the end of a standardized early rehabilitation session
      helped us to ensure the safety of our protocol. CLINICAL REHABILITATION IMPACT:
      Because of its feasibility, safety and reproducibility our rehabilitation
      treatment has been applied to different types of surgical inpatients in order to
      limit the negative consequences of immobilization.

PMID- 26220329
TI  - Effectiveness of adaptive physical activity combined with therapeutic patient
      education in stroke survivors at twelve months: a non-randomized parallel group
      study.
AB  - BACKGROUND: Adaptive physical activity (APA) is a community-based exercise
      program for chronic stroke survivors that proved to be effective in improving
      physical functioning and psychological well-being in the short term. AIM: The aim
      of the present paper is to determine the effectiveness at twelve months of an
      intervention of APA combined with therapeutic patient education (TPE) in stroke
      survivors. DESIGN: This study is a non-randomized parallel group study comparing
      APA-TPE intervention with treatment as usual (TAU). SETTING: Patients were
      recruited after discharge from two Physical Medicine and Rehabilitation Units, 3
      to 18 months after the stroke event. The APA-TPE intervention was conducted in
      local gymnasiums. POPULATION: The study population includes consecutive adult
      stroke survivors with mild to moderate hemiparesis who were able to walk 25 m
      independently and had no need of physical therapy. METHODS: The experimental
      group (N.=126) underwent 16 biweekly sessions of APA and 3 TPE sessions and
      controls (N.=103) underwent TAU. Twelve-month outcomes included the Modified
      Barthel Index, the Caregiver Strain Index, SF-12 health-related quality of life,
      medical complications and health services use. RESULTS: At twelve months, the
      ability to perform daily living activities, assessed using Modified Barthel
      Index, was decreased in the TAU group and improved in the APA-TPE group. The
      physical and mental components of quality of life were significantly improved in
      both groups. The risk of fractures (OR=0.09, 95% CI 0.01-0.79) and recourse to
      rehabilitation treatments (OR=0.24, 95% CI 0.08-0.77) were lower in the APA-TPE
      compared with the TAU group. No difference was found between groups concerning
      the caregiver burden. CONCLUSION: APA-TPE is an effective intervention to
      maintain and improve activities of daily living, reduce falls and recourse to
      rehabilitation treatments at twelve months. CLINICAL REHABILITATION IMPACT:
      Structured physical activity programs that can be performed also at home, when
      combined with therapeutic education focused on benefits of physical activity,
      will encourage stroke survivors to continue exercising. Therefore, it fulfills an
      essential requirement to the maintenance of lasting health benefits and the
      prevention of physical and psychological deterioration.

PMID- 26220330
TI  - Cyclin Y inhibits plasticity-induced AMPA receptor exocytosis and LTP.
AB  - Cyclin Y (CCNY) is a member of the cyclin protein family, known to regulate cell
      division in proliferating cells. Interestingly, CCNY is expressed in neurons that
      do not undergo cell division. Here, we report that CCNY negatively regulates long
      term potentiation (LTP) of synaptic strength through inhibition of AMPA receptor
      trafficking. CCNY is enriched in postsynaptic fractions from rat forebrain and is
      localized adjacent to postsynaptic sites in dendritic spines in rat hippocampal
      neurons. Using live-cell imaging of a pH-sensitive AMPA receptor, we found that
      during LTP-inducing stimulation, CCNY inhibits AMPA receptor exocytosis in
      dendritic spines. Furthermore, CCNY abolishes LTP in hippocampal slices. Taken
      together, our findings demonstrate that CCNY inhibits plasticity-induced AMPA
      receptor delivery to synapses and thereby blocks LTP, identifying a novel
      function for CCNY in post-mitotic cells. 

PMID- 26220331
TI  - Insensitivity of well-conditioned mature sheep to central administration of a
      leptin receptor antagonist.
AB  - Ruminants remain productive during the energy insufficiency of late pregnancy or
      early lactation by evoking metabolic adaptations sparing available energy and
      nutrients (e.g. higher metabolic efficiency and induction of insulin resistance).
      A deficit in central leptin signaling triggers these adaptations in rodents but
      whether it does in ruminants remains unclear. To address this issue, five mature
      ewes were implanted with intracerebroventricular (ICV) cannula in the third
      ventricle. They were used in two experiments with an ovine leptin antagonist
      (OLA) when well-conditioned (average body condition score of 3.7 on a 5 point
      scale). The first experiment tested the ability of OLA to antagonize leptin under
      in vivo conditions. Ewes received continuous ICV infusion of artificial
      cerebrospinal fluid (aCSF), ovine leptin (4 ug/h) or the combination of ovine
      leptin (4 ug/h) and its mutant version OLA (40 ug/h) for 48 h. Dry matter intake
      (DMI) was measured every day and blood samples were collected on the last day of
      infusion. ICV infusion of leptin reduced DMI by 24% (P < 0.05), and this effect
      was completely abolished by OLA co-infusion. A second experiment tested whether a
      reduction in endogenous leptin signaling in the brain triggers metabolic
      adaptations. This involved continuous ICV infusions of aCSF or OLA alone (40
      ug/h) for 4 consecutive days. The infusion of OLA did not alter voluntary DMI
      over the treatment period or on any individual day. OLA did not affect plasma
      variables indicative of insulin action (glucose, non-esterified fatty acids,
      insulin and the disposition of plasma glucose during an insulin tolerance test)
      or plasma cortisol, but tended to reduce plasma triiodothyronine and thyroxine (P
      < 0.07). Overall, these data show that a reduction of central leptin signaling
      has little impact on insulin action in well-conditioned mature sheep. They also
      raise the possibility that reduced central leptin signaling plays a role in
      controlling thyroid hormone production.

PMID- 26220332
TI  - Treatment of full-thickness femoral cartilage lesions using condyle resurfacing
      prosthesis.
AB  - PURPOSE: The HemiCAP(r) implant for femoral resurfacing treatment of cartilage
      lesions was introduced in 2003. We present outcome from a prospective cohort
      study of 61 patients with both trochleal and condylar lesions treated with the
      HemiCAP(r) implant. METHODS: From 2007 to 2012, 61 patients were treated with
      femoral resurfacing using the HemiCAP implant. There were 36 femoral condyle
      implants and 25 trochleal implants. Indication for treatment with HemiCAP implant
      was symptomatic cartilage lesion at the femoral condyle demonstrated by MRI or
      arthroscopy, which was ICRS grade 3-4 and size less than 4 cm2. There were 24
      males and 37 females with a median age of 49 (range 35-65) years. Patients were
      followed for 2 years with Knee Society subjective outcome scores (KSS), pain
      scores and radiographic evaluations and for 7 years with complications and
      reoperations. RESULTS: At 2-year follow-up, mean KSS was improved from 52 (6.2)
      to 90 (7.9), mean KSS function score was improved from 45 (7.5) to 92 (8.3), and
      mean Pain score improved from 7.1 (0.7) to 1.8 (1.7). Twenty-three per cent of
      implants were revised within 7 years to arthroplasty due to progression of
      cartilage lesions, progression of osteoarthritis, or increased knee pain. No
      difference between females and males was found for reoperation rate. CONCLUSION:
      The present study demonstrated improved subjective outcome and reduced pain after
      femoral resurfacing using the HemiCAP implant in a relatively large cohort of
      patients with symptomatic cartilage lesions. A concerning 23 % reoperation rate
      with conversion to arthroplasty was found. Femoral resurfacing implantation
      treatment can be a temporary treatment for cartilage lesions expected to develop
      into osteoarthritis and for younger patients not eligible for arthroplasty
      treatment. LEVEL OF EVIDENCE: IV.

PMID- 26220340
TI  - Shiga-like toxin-based high-efficiency and receptor-specific intracellular
      delivery system for a protein.
AB  - The cell-specific cytosolic delivery of functional macromolecules with high
      efficiency is of great significance in molecular medicine and biotechnology.
      Herein, we present a Shiga-like toxin II-based high-efficiency and receptor
      specific intracellular delivery system. We designed and constructed the Shiga
      like toxin-based carrier (STC) to comprise the targeting and translocation
      domains, and used it for delivering a protein cargo. The STC was shown to deliver
      a protein cargo into the cytosol with high efficiency in a receptor-specific
      manner, exhibiting much higher efficiency than the most widely used cell
      penetrating peptide. The general utility of the STC was demonstrated by
      modulating the targeting domain. The present delivery platform can be widely used
      for the intracellular delivery of diverse biomolecules in a receptor-specific and
      genetically encodable manner. 

PMID- 26220341
TI  - Overexpression of Arl6ip5 in osteoblast regulates RANKL subcellualr localization.
AB  - The osteoblastic expression of RANKL, which is essential for the communication
      between osteoblastic cells and osteoclastogenic cells, is stimulated by locally
      acting or circulating osteotropic cytokines and hormones such as PTH and 1,25
      (OH)2-D3 during the bone remodeling process. However, mechanisms those control
      subcellular trafficking events, membrane expression and extracellular secretion
      of the newly synthesized RANKL are still not well understood. In our previous
      study, we have found that the deficiency of osteoblastic Arl6ip5 (ADP
      ribosylation-like factor 6 interacting protein 5), an endoplasmic reticulum (ER)
      localized protein belonging to the prenylated rab-acceptor-family, enhanced
      osteoclastogenesis by increasing RANKL transcription in an ER stress dependent
      signaling. Here we found that over-expression of hemagglutinin (HA)-tagged
      Arl6ip5 in UAMS32 stromal/osteoblastic cells inhibited osteoclastogenesis,
      decreased the amount of soluble RANKL in culture supernatant and increased RANKL
      retention in ER. Moreover, Arl6ip5 bound with RANKL and disturbed the RANKL-OPG
      complex in UAMS-32 cells. Finally, 1 to 36 amino acid deletion on the NH2 lumen
      terminus of Arl6ip5 impaired the interaction between Arl6ip5 and RANKL, restored
      the level of soluble RANKL and the osteoclastogenic ability. These findings
      indicated that Arl6ip5 was an anti-catabolic factor by binding with RANKL and
      disturbing its subcellular trafficking in osteoblast. 

PMID- 26220342
TI  - Astragaloside IV suppresses transforming growth factor-beta1 induced fibrosis of
      cultured mouse renal fibroblasts via inhibition of the MAPK and NF-kappaB
      signaling pathways.
AB  - Renal fibrosis, a progressive process characterized by the accumulation of
      extracellular matrix (ECM) leading to organ dysfunction, is a characteristic of
      chronic kidney diseases. Among fibrogenic factors known to regulate the renal
      fibrotic process, transforming growth factor-beta (TGF-beta) plays a central
      role. In the present study, we examined the effect of Astragaloside IV (AS-IV), a
      component of the traditional Chinese medicinal plant Astragalus membranaceus, on
      the processes associated with renal fibrosis in cultured mouse renal fibroblasts
      treated with TGF-beta1. RT-PCR, western blotting, immunofluorescence staining and
      collagen assays showed that AS-IV suppressed TGF-beta1 induced fibroblast
      proliferation, transdifferentiation, and ECM production in a dose-dependent
      manner. Examination of the underlying mechanisms showed that the effect of AS-IV
      on the inhibition of fibroblast differentiation and ECM formation were mediated
      by its modulation of the activity of the MAPK and NF-kappaB signaling pathways.
      Taken together, our results indicate that AS-IV alleviates renal interstitial
      fibrosis via a mechanism involving the MAPK and NF-kappaB signaling pathways and
      demonstrate the therapeutic potential of AS-IV for the treatment of chronic
      kidney diseases. 

PMID- 26220343
TI  - Expression and potential role of the peptide orexin-A in prostate cancer.
AB  - The peptides orexin-A and orexin-B and their G protein-coupled OX1 and OX2
      receptors are involved in multiple physiological processes in the central nervous
      system and peripheral organs. Altered expression or signaling dysregulation of
      orexins and their receptors have been associated with a wide range of human
      diseases including narcolepsy, obesity, drug addiction, and cancer. Although
      orexin-A, its precursor molecule prepro-orexin and OX1 receptor have been
      detected in the human normal and hyperplastic prostate tissues, their expression
      and function in the prostate cancer (PCa) remains to be addressed. Here, we
      demonstrate for the first time the immunohistochemical localization of orexin-A
      in human PCa specimens, and the expression of prepro-orexin and OX1 receptor at
      both protein and mRNA levels in these tissues. Orexin-A administration to the
      human androgen-dependent prostate carcinoma cells LNCaP up-regulates OX1 receptor
      expression resulting in a decrease of cell survival. Noteworthy, nanomolar
      concentrations of the peptide counteract the testosterone-induced nuclear
      translocation of the androgen receptor in the cells: the orexin-A action is
      prevented by the addition of the OX1 receptor antagonist SB-408124 to the test
      system. These findings indicate that orexin-A/OX1 receptor interaction interferes
      with the activity of the androgen receptor which regulates PCa onset and
      progression, thus suggesting that orexin-A and its receptor might represent novel
      therapeutic targets to challenge this aggressive cancer. 

PMID- 26220345
TI  - Lack of enzyme activity in GBA2 mutants associated with hereditary spastic
      paraplegia/cerebellar ataxia (SPG46).
AB  - Glucosylceramide is a membrane glycolipid made up of the sphingolipid ceramide
      and glucose, and has a wide intracellular distribution. Glucosylceramide is
      degraded to ceramide and glucose by distinct, non-homologous enzymes, including
      glucocerebrosidase (GBA), localized in the endolysosomal pathway, and beta
      glucosidase 2 (GBA2), which is associated with the plasma membrane and/or the
      endoplasmic reticulum. It is well established that mutations in the GBA gene
      result in endolysosomal glucosylceramide accumulation, which triggers Gaucher
      disease. In contrast, the biological significance of GBA2 is less well
      understood. GBA2-deficient mice present with male infertility, but humans
      carrying mutations in the GBA2 gene are affected with a combination of cerebellar
      ataxia and spastic paraplegia, as well as with thin corpus callosum and cognitive
      impairment (SPastic Gait locus #46, SPG46). To improve our understanding of the
      biochemical consequences of the GBA2 mutations, we have evaluated five nonsense
      and five missense GBA2 mutants for their enzyme activity. In transfected cells,
      the mutant forms of GBA2 were present in widely different amounts, ranging from
      overabundant to very minor, compared to the wild type enzyme. Nevertheless, none
      of the GBA2 mutant cDNAs raised the enzyme activity in transfected cells, in
      contrast to the wild-type enzyme. These results suggest that SPG46 patients have
      a severe deficit in GBA2 activity, because the GBA2 mutants are intrinsically
      inactive and/or reduced in amount. This assessment of the expression levels and
      enzyme activities of mutant forms of GBA2 offers a first insight in the
      biochemical basis of the complex pathologies seen in SPG46. 

PMID- 26220344
TI  - ADCY7 supports development of acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is the most common adult acute leukemia. Despite
      treatment, the majority of the AML patients relapse within 5 years. In silico
      analysis of several available databases of AML patients showed that the
      expression of adenylate cyclase 7 (ADCY7) significantly inversely correlates with
      the overall survival of AML patients. To determine whether ADCY7 supports AML
      development, we employed an shRNA-encoding lentivirus system to inhibit adcy7
      expression in human AML cells including U937, MV4-11, and THP-1 cells. The ADCY7
      deficiency resulted in decreased cell growth, elevated apoptosis, and lower c-Myc
      expression of these leukemia cells. This indicates that G protein-coupled
      receptor signaling contributes to AML pathogenesis. Our study suggests that
      inhibition of ADCY7 may be novel strategy for treating leukemia. 

PMID- 26220346
TI  - Applications of three-dimensional printing technology in the cardiovascular
      field.
AB  - Three-dimensional (3-D) printing technology has rapidly developed in the last few
      decades. Meanwhile, the application of this technology has reached beyond the
      engineering field and expanded to almost all disciplines, including medicine.
      There has been much research on the medical applications of 3-D printing in
      neurosurgery, orthopedics, maxillofacial surgery, plastic surgery, tissue
      engineering, as well as other fields. Because of the complexity of the
      cardiovascular system, the application of this technology is limited and
      difficult, as compared to other disciplines, and thus there is much room for
      future development. Many of the difficulties associated with this technology must
      be overcome. Nonetheless, there is no doubt that 3-D printing technology will
      benefit patients with cardiovascular diseases in the near future. 

PMID- 26220348
TI  - Inhibition of 11beta-HSD1 by LG13 improves glucose metabolism in type 2 diabetic
      mice.
AB  - 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) controls the production
      of active glucocorticoid (GC) and has been proposed as a new target for the
      treatment of type 2 diabetes. We have previously reported that a natural product,
      curcumin, exhibited moderate inhibition and selectivity on 11beta-HSD1. By
      analyzing the models of protein, microsome, cells and GCs-induced mice in vitro
      and in vivo, this study presented a novel curcumin analog, LG13, as a potent
      selective 11beta-HSD1 inhibitor. In vivo, Type 2 diabetic mice were treated with
      LG13 for 42 days to assess the pharmacological benefits of 11beta-HSD1 inhibitor
      on hepatic glucose metabolism. In vitro studies revealed that LG13 selectively
      inhibited 11beta-HSD1 with IC50 values at nanomolar level and high selectivity
      over 11beta-HSD2. Targeting 11beta-HSD1, LG13 could inhibit prednisone-induced
      adverse changes in mice, but had no effects on dexamethasone-induced ones.
      Further, the 11beta-HSD1 inhibitors also suppressed 11beta-HSD1 and GR
      expression, indicating a possible positive feedback system in the 11beta-HSD1/GR
      cycle. In type 2 diabetic mice induced by high fat diet plus low-dosage STZ
      injection, oral administration with LG13 for 6 weeks significantly decreased
      fasting blood glucose, hepatic glucose metabolism, structural disorders, and
      lipid deposits. LG13 exhibited better pharmacological effects in vivo than
      insulin sensitizer pioglitazone and potential 11beta-HSD1 inhibitor PF-915275.
      These pharmacological and mechanistic insights on LG13 also provide us novel
      agents, leading structures, and strategy for the development of 11beta-HSD1
      inhibitors treating metabolic syndromes. 

PMID- 26220347
TI  - Functions of DPLIY motif and helix 8 of human melanocortin-3 receptor.
AB  - The melanocortin-3 receptor (MC3R) is a member of the family A G protein-coupled
      receptors (GPCRs). The MC3R remains the most enigmatic of the melanocortin
      receptors with regard to its physiological functions, especially its role in
      energy homeostasis. The N/DPxxY motif and the eighth helix (helix 8) in the
      carboxyl terminus of GPCRs have been identified to be important for receptor
      expression, ligand binding, signal transduction and internalization. To gain a
      better understanding of the structure-function relationship of MC3R, we performed
      a systematic study of all 20 residues in this domain using alanine-scanning
      mutagenesis. We showed that although all mutants were expressed normally on the
      cell surface, eleven residues were important for ligand binding and one was
      indispensable for downstream cAMP generation. F347A showed constitutive activity
      in cAMP signaling while all the other mutants had normal basal activities. We
      studied the signaling capacity of nine mutants in the ERK1/2 signaling pathway.
      All of these mutants showed normal basal ERK1/2 phosphorylation levels. The
      pERK1/2 levels of six binding- or signaling-defective mutants were enhanced upon
      agonist stimulation. The unbalanced cAMP and pERK1/2 signaling pathways suggested
      the existence of biased signaling in MC3R mutants. In summary, we showed that the
      DPLIY motif and helix 8 was important for MC3R activation and signal
      transduction. Our data led to a better understanding of the structure-function
      relationship of MC3R. 

PMID- 26220349
TI  - Postoperative Course and Complications after Pull-through Vaginoplasty for Distal
      Vaginal Atresia.
AB  - STUDY OBJECTIVE: To report the usual postoperative course and complications after
      pull-through vaginoplasty for isolated distal vaginal atresia. DESIGN, SETTING,
      AND PARTICIPANTS: Retrospective chart review at Texas Children's Hospital of all
      patients who were diagnosed with isolated distal vaginal atresia and underwent
      pull-through vaginoplasty during the study time frame. INTERVENTIONS: None. MAIN
      OUTCOME MEASURES: Postoperative complications such as vaginal stenosis or
      infection and postoperative vaginal diameter. RESULTS: Sixteen patients were
      identified and charts were reviewed. Patients were initially evaluated by pelvic
      magnetic resonance imaging and found to have distended hematometrocolpos with
      distal vaginal atresia. All patients underwent pull-through vaginoplasty with
      similar operative techniques. The average distance from the perineum to the level
      of the obstruction was 1.84 +/- 1.2 cm. Two patients, both with obstructions at
      greater than 3 cm, experienced stricture formation postoperatively. Four patients
      (25%) experienced postoperative vaginitis. One patient (6.25%) experienced a
      postoperative urinary tract infection. Two groups (3 cm or less versus greater
      than 3 cm) were compared, and the presence of stricture was statistically
      different based on mean centimeters from perineum prior to pull-through
      vaginoplasty (P = .038). CONCLUSIONS: Distal vaginal atresia is managed with pull
      through vaginoplasty. Atresias that extend greater than 3 cm from the perineum
      are at increased risk for vaginal stricture formation and should be followed to
      monitor for their formation. Other complications are infrequent and minor.

PMID- 26220350
TI  - Epithelial Tumors of the Ovary in Children and Teenagers: A Prospective Study
      from the Italian TREP Project.
AB  - STUDY OBJECTIVE: To report the clinical findings and treatment results of a
      series of patients with epithelial tumors of the ovary, registered and treated
      prospectively in a multi-institutional Italian network (TREP project) on rare
      tumors in children and adolescent between 2000 and 2014. DESIGN, SETTING, AND
      PARTICIPANTS: Data on 16 patients, aged 22 to 206 months, from 7 centers were
      reviewed. All patients were grouped on the basis of the results of the first
      surgical approach, according to the Children Oncology Group staging system.
      RESULTS: The most frequent symptom was abdominal pain; 3 patients were
      hospitalized for acute pain after ovarian torsion. Initial surgical treatment was
      complete in 15 of 16, and a biopsy was performed in 1 of 16. The histology
      examination revealed 8 benign tumors (7 mucinous cystadenomas and 1 serous
      cystadenoma) and 8 borderline tumors (2 serous and 6 mucinous). Fifteen of 16
      patients maintained the complete remission after surgical treatment alone; 1
      affected by Proteus syndrome died consequent to the progression of a synchronous
      Wilms tumor, after a delayed incomplete surgery. CONCLUSION: Our analysis
      documented the rarity of these tumors in children and adolescents. No malignant
      histologies were found. Surgery alone was effective to cure the majority of
      patients. Considering the rarity of malignant entities, ovary-sparing surgery may
      be planned when an epithelial tumor is suspected on the basis of the preoperative
      work-up and intraoperative findings.

PMID- 26220351
TI  - The Impact of Health Education Counseling on Rate of Recurrent Sexually
      Transmitted Infections in Adolescents.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of a sexually transmitted
      infection (STI) intervention by a health educator that included partner
      notification, condom use, and retesting within 3 months. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective chart review was conducted, and data were collected
      from 274 sexually active adolescent girls, aged 15 to 19 years, who were
      diagnosed with gonorrhea (GC), Chlamydia (CT), and Trichomonas (TV) infection,
      during a 9-month span in an urban hospital-based adolescent medicine clinic.
      METHODS: Data regarding recurrent STIs (GC, CT, and TV) were collected for 12
      months following the incident infection. There were 161 in the intervention group
      (health educator counseling), and 113 controls who received usual care.
      Differences between groups were analyzed using chi(2) and survival analyses.
      RESULTS: There were no significant differences in age, gender, or race between
      the intervention and control groups at baseline. The majority in both groups were
      diagnosed initially with CT infection (57% CT, 16% GC, and 5% TV in the
      intervention group; 46% CT, 21% GC, and 12% TV in the control group). There was a
      significantly lower rate of STI in the intervention group for those retested
      within 12 months of the initial diagnosis (P = .002). The median (SD) time to
      recurrence in the intervention group was greater: 134 (14.7) days versus 116
      (12.1) days (P = .034). Health education counseling, initial diagnosis with TV,
      and duration of time from initial diagnosis to retest (interval to retest) were
      significant protective factors for recurrent STI. CONCLUSIONS: Health education
      counseling in an urban adolescent clinic is effective in reducing recurrent
      infection at 12-month follow-up and can serve as an important component in
      reducing STI recidivism.

PMID- 26220353
TI  - Autoimmune Encephalitis Following Bone Marrow Transplantation.
AB  - BACKGROUND: Neurological complications, especially encephalopathy and seizures,
      are commonly seen in bone marrow transplant patients. Infections, chemotoxicity,
      graft versus host disease, or secondary central nervous system malignancies are
      the most common underlying etiologies. There is increased awareness that
      autoimmune encephalitis may cause neurological dysfunction in immunocompetent
      children. The potential role of such a mechanism in children undergoing bone
      marrow transplantation is unknown. METHODS: We report a boy who developed
      autoimmune encephalitis with voltage-gated potassium channel-associated and
      thyroid autoantibodies subsequent to transplantation. RESULTS: A 7-year-old boy
      presented with a change in behavior, poor attention, cognitive deficits, and
      abnormal movements 15 months after undergoing transplantation for idiopathic
      aplastic anemia. He had clinical and subclinical seizures and brain magnetic
      resonance imaging hyperintensities bilaterally in the uncal regions. His
      evaluation revealed high titers of voltage-gated potassium channel, leucine-rich
      glioma-inactivated 1 protein, and thyroglobulin antibodies suggestive of
      autoimmune limbic encephalitis. He showed significant improvement in behavior and
      neuropsychological testing and has remained seizure-free on levetiracetam after
      immunotherapy with corticosteroids and intravenous immunoglobulin. CONCLUSION:
      Systemic autoimmune manifestations in bone marrow transplant patients have been
      well-documented, but autoimmune encephalitis after transplantation has yet to be
      described in children.

PMID- 26220352
TI  - Updated Guidelines for the Medical Assessment and Care of Children Who May Have
      Been Sexually Abused.
AB  - The medical evaluation is an important part of the clinical and legal process
      when child sexual abuse is suspected. Practitioners who examine children need to
      be up to date on current recommendations regarding when, how, and by whom these
      evaluations should be conducted, as well as how the medical findings should be
      interpreted. A previously published article on guidelines for medical care for
      sexually abused children has been widely used by physicians, nurses, and nurse
      practitioners to inform practice guidelines in this field. Since 2007, when the
      article was published, new research has suggested changes in some of the
      guidelines and in the table that lists medical and laboratory findings in
      children evaluated for suspected sexual abuse and suggests how these findings
      should be interpreted with respect to sexual abuse. A group of specialists in
      child abuse pediatrics met in person and via online communication from 2011
      through 2014 to review published research as well as recommendations from the
      Centers for Disease Control and Prevention and the American Academy of Pediatrics
      and to reach consensus on if and how the guidelines and approach to
      interpretation table should be updated. The revisions are based, when possible,
      on data from well-designed, unbiased studies published in high-ranking, peer
      reviewed, scientific journals that were reviewed and vetted by the authors. When
      such studies were not available, recommendations were based on expert consensus. 

PMID- 26220354
TI  - Neurological Outcomes After Presumed Childhood Encephalitis.
AB  - OBJECTIVE: To evaluate factors during acute presumed childhood encephalitis that
      are associated with development of long-term neurological sequelae. METHODS: A
      total of 217 patients from Rady Children's Hospital San Diego with suspected
      encephalitis who met criteria for the California Encephalitis Project were
      identified. A cohort of 99 patients (40 females, 59 males, age 2 months-17 years)
      without preexisting neurological conditions, including prior seizures or abnormal
      brain magnetic resonance imaging scans was studied. Mean duration of follow-up
      was 29 months. Factors that had a relationship with the development of
      neurological sequelae (defined as developmental delay, learning difficulties,
      behavioral problems, or focal neurological findings) after acute encephalitis
      were identified. RESULTS: Neurological sequelae at follow-up was associated with
      younger age (6.56 versus 9.22 years) at presentation (P = 0.04) as well as an
      initial presenting sign of seizure (P = 0.03). Duration of hospital stay (median
      of 7 versus 15.5 days; P = 0.02) was associated with neurological sequelae. Of
      the patients with neurological sequelae, a longer hospital stay was associated
      with patients of an older age (P = 0.04). Abnormalities on neuroimaging (P =
      1.00) or spinal fluid analysis (P = 1.00) were not uniquely associated with
      neurological sequelae. Children who were readmitted after their acute illness (P
      = 0.04) were more likely to develop neurological sequelae. There was a strong
      relationship between the patients who later developed epilepsy and those who
      developed neurological sequelae (P = 0.02). SIGNIFICANCE: Limited data are
      available on the long-term neurological outcomes of childhood encephalitis.
      Almost half of our patients were found to have neurological sequelae at follow
      up, indicating the importance of earlier therapies to improve neurological
      outcome.

PMID- 26220355
TI  - Tumour response, correlates of survival and clinical benefit.

PMID- 26220356
TI  - Mutation of G234 amino acid residue in candida albicans drug-resistance-related
      protein Rta2p is associated with fluconazole resistance and dihydrosphingosine
      transport.
AB  - Widespread and repeated use of azoles has led to the rapid development of drug
      resistance in Candida albicans. Our previous study found Rta2p, a membrane
      protein with 7 transmembrane domains, was involved in calcineurin-mediated azole
      resistance and sphingoid long-chain base release in C. albicans. Conserved amino
      acids in the transmembrane domain of Rta2p were subjected to site-directed
      mutagenesis. The sensitivity of C. albicans to fluconazole in vitro was examined
      by minimum inhibitory concentration and killing assay, and the therapeutic
      efficacy of fluconazole in vivo was performed by systemic mice candidiasis model.
      Furthermore, dihydrosphingosine transport activity was detected by NBD labeled D
      erythro-dihydrosphingosine uptake and release assay, and the sensitivity to
      sphingolipid biosynthesis inhibitors. We successfully constructed 14 mutant
      strains of Rta2p, screened them by minimum inhibitory concentration and found
      Ca(2+) did not completely induce fluconazole resistance with G158E and G234S
      mutations. Furthermore, we confirmed that G234S mutant enhanced the therapeutic
      efficacy of fluconazole against systemic candidiasis and significantly increased
      the accumulation of dihydrosphingosine by decreasing its release. However, G158E
      mutant didn't affect drug therapeutic efficacy in vivo and dihydrosphingosine
      transport in C. albicans. G234 of Rta2p in C. albicans is crucial in calcineurin
      mediated fluconazole resistance and dihydrosphingosine transport. 

PMID- 26220357
TI  - Bilateral subclavian vein sheaths for superior vena cava drainage during
      thoracoscopic repair of atrial septal defects: cosmetic outcomes, safety and
      effectiveness.
AB  - OBJECTIVE: To investigate the cosmetic outcomes, safety and effectiveness of
      using bilateral subclavian vein sheaths for superior vena cava drainage during
      thoracoscopic repair of atrial septal defects. METHODS: Sixty-one consecutive
      adults scheduled for thoracoscopic repair of atrial septal defects between July
      2012 and June 2013 were randomized into two groups: one group underwent placement
      of a 16 Fr percutaneous superior vena cava cannula (n = 30) and the other group
      underwent placement of bilateral 8 Fr subclavian vein sheaths (n = 31) for
      superior vena cava drainage during peripheral cardiopulmonary bypass. The
      perioperative data, central venous pressure during cardiopulmonary bypass,
      complications and the patient satisfaction scale scores for the incisions were
      compared between the two groups. RESULTS: The theoretical cardiopulmonary bypass
      flow rate was reached without complications in all patients. The average central
      venous pressure during cardiopulmonary bypass was not significantly different
      between the two groups [(6.9 +/- 3.1) mmHg vs. (7.0 +/- 3.5) mmHg, p=0.92]. The
      patient satisfaction scale scores for the incisions were significantly higher in
      the patients who underwent placement of bilateral subclavian vein sheaths than in
      the patients who underwent placement of a percutaneous superior vena cava cannula
      [(2.81 +/- 0.75) vs. (2.07 +/- 0.74), p<0.001]. CONCLUSIONS: Placement of
      bilateral subclavian vein sheaths is a safe and effective alternative to
      placement of a percutaneous superior vena cava cannula for superior vena cava
      drainage during thoracoscopic repair of atrial septal defects and results in
      greater patient satisfaction with the cosmetic outcome.

PMID- 26220358
TI  - Reliability of the Thoratec HeartMate II flow measurements and alarms in the
      presence of reduced or non-existent flow.
AB  - INTRODUCTION: The Thoratec Corporation has over 10,000 patients registered as
      recipients of the HeartMate II left ventricular assist device (LVAD) worldwide.
      Although it has undoubtedly prolonged the lifespan of heart failure patients, the
      most recognized risk associated with these devices is the development of
      thrombus. In the presence of a small or developing clot, the HeartMate II display
      module and system monitor indicate that there is a decrease in pump flow, adjusts
      its pump power and is accompanied by audible and visual alarms when flow rates
      drop below a fixed threshold established by Thoratec. In contrast, when thrombus
      completely inhibits flow through the device, the display module and system
      monitor have failed in previous case studies to indicate that flow has reduced to
      zero and do not produce any corresponding alarms. METHODS: To test the efficacy
      of the HeartMate II alarms, a cardiovascular simulation tank was used to
      reproduce the hemodynamics of a typical heart failure patient. The hemodynamics
      were then improved by the addition of the HeartMate II LVAD and different partial
      and complete occlusions were applied to the inlet and outlet of the HeartMate II
      pump. CONCLUSIONS: Partially occluding the inflow and/or outflow of the HeartMate
      II did display changes in flow and presented with alarms when flow was estimated
      to be below 2.5 L/min; however, complete occlusion of the inflow and/or outflow
      failed to produce any alarms or accurately measured changes in flow.

PMID- 26220359
TI  - Characterization of the genome and transcriptome of the blue tit Cyanistes
      caeruleus: polymorphisms, sex-biased expression and selection signals.
AB  - Decoding genomic sequences and determining their variation within populations has
      potential to reveal adaptive processes and unravel the genetic basis of
      ecologically relevant trait variation within a species. The blue tit Cyanistes
      caeruleus--a long-time ecological model species--has been used to investigate
      fitness consequences of variation in mating and reproductive behaviour. However,
      very little is known about the underlying genetic changes due to natural and
      sexual selection in the genome of this songbird. As a step to bridge this gap, we
      assembled the first draft genome of a single blue tit, mapped the transcriptome
      of five females and five males to this reference, identified genomewide variants
      and performed sex-differential expression analysis in the gonads, brain and other
      tissues. In the gonads, we found a high number of sex-biased genes, and of those,
      a similar proportion were sex-limited (genes only expressed in one sex) in males
      and females. However, in the brain, the proportion of female-limited genes within
      the female-biased gene category (82%) was substantially higher than the
      proportion of male-limited genes within the male-biased category (6%). This
      suggests a predominant on-off switching mechanism for the female-limited genes.
      In addition, most male-biased genes were located on the Z-chromosome, indicating
      incomplete dosage compensation for the male-biased genes. We called more than
      500,000 SNPs from the RNA-seq data. Heterozygote detection in the single
      reference individual was highly congruent between DNA-seq and RNA-seq calling.
      Using information from these polymorphisms, we identified potential selection
      signals in the genome. We list candidate genes which can be used for further
      sequencing and detailed selection studies, including genes potentially related to
      meiotic drive evolution. A public genome browser of the blue tit with the
      described information is available at http://public-genomes-ngs.molgen.mpg.de.

PMID- 26220360
TI  - Bilateral atrophoderma linearis: a relationship between atrophoderma linearis
      Moulin and atrophoderma Pasini-Pierini?

PMID- 26220361
TI  - The "Big Bang" in obese fat: Events initiating obesity-induced adipose tissue
      inflammation.
AB  - Obesity is associated with the accumulation of pro-inflammatory cells in visceral
      adipose tissue (VAT), which is an important underlying cause of insulin
      resistance and progression to diabetes mellitus type 2 (DM2). Although the role
      of pro-inflammatory cytokines in disease development is established, the
      initiating events leading to immune cell activation remain elusive. Lean adipose
      tissue is predominantly populated with regulatory cells, such as eosinophils and
      type 2 innate lymphocytes. These cells maintain tissue homeostasis through the
      excretion of type 2 cytokines, such as IL-4, IL-5, and IL-13, which keep adipose
      tissue macrophages (ATMs) in an anti-inflammatory, M2-like state. Diet-induced
      obesity is associated with the loss of tissue homeostasis and development of type
      1 inflammatory responses in VAT, characterized by IFN-gamma. A key event is a
      shift of ATMs toward an M1 phenotype. Recent studies show that obesity-induced
      adipocyte hypertrophy results in upregulated surface expression of stress
      markers. Adipose stress is detected by local sentinels, such as NK cells and
      CD8(+) T cells, which produce IFN-gamma, driving M1 ATM polarization. A rapid
      accumulation of pro-inflammatory cells in VAT follows, leading to inflammation.
      In this review, we provide an overview of events leading to adipose tissue
      inflammation, with a special focus on adipose homeostasis and the obesity-induced
      loss of homeostasis which marks the initiation of VAT inflammation. 

PMID- 26220363
TI  - Energy dissipation pathways in Photosystem 2 of the diatom, Phaeodactylum
      tricornutum, under high-light conditions.
AB  - To prevent photooxidative damage under supraoptimal light, photosynthetic
      organisms evolved mechanisms to thermally dissipate excess absorbed energy, known
      as non-photochemical quenching (NPQ). Here we quantify NPQ-induced alterations in
      light-harvesting processes and photochemical reactions in Photosystem 2 (PS2) in
      the pennate diatom Phaeodactylum tricornutum. Using a combination of picosecond
      lifetime analysis and variable fluorescence technique, we examined the dynamics
      of NPQ activation upon transition from dark to high light. Our analysis revealed
      that NPQ activation starts with a 2-3-fold increase in the rate constant of non
      radiative charge recombination in the reaction center (RC); however, this
      increase is compensated with a proportional increase in the rate constant of back
      reactions. The resulting alterations in photochemical processes in PS2 RC do not
      contribute directly to quenching of antenna excitons by the RC, but favor non
      radiative dissipation pathways within the RC, reducing the yields of spin
      conversion of the RC chlorophyll to the triplet state. The NPQ-induced changes in
      the RC are followed by a gradual ~ 2.5-fold increase in the yields of thermal
      dissipation in light-harvesting complexes. Our data suggest that thermal
      dissipation in light-harvesting complexes is the major sink for NPQ; RCs are not
      directly involved in the NPQ process, but could contribute to photoprotection via
      reduction in the probability of (3)Chl formation.

PMID- 26220362
TI  - Wnt/beta-Catenin-Responsive Cells in Prostatic Development and Regeneration.
AB  - The precise role of Wnt/beta-catenin signaling during prostatic development and
      tumorigenesis is unclear. Axin2 is a direct transcriptional target of beta
      catenin. Recent studies have shown that Axin2-expressing cells have
      stem/progenitor cell properties in a variety of mouse tissues. Here, we
      genetically labeled Axin2-expressing cells at various time points and tracked
      their cellular behavior at different developmental and mature stages. We found
      that prostatic Axin2-expressing cells mainly express luminal epithelial cell
      markers and are able to expand luminal cell lineages during prostatic development
      and maturation. They can also survive androgen withdrawal and regenerate
      prostatic luminal epithelial cells following androgen replacement. Deletion of
      beta-catenin or expression of stabilized beta-catenin in these Axin2-expressing
      cells results in abnormal development or oncogenic transformation, respectively.
      Our study uncovers a critical role of Wnt/beta-catenin-responsive cells in
      prostatic development and regeneration, and that dysregulation of Wnt/beta
      catenin signaling in these cells contributes to prostatic developmental defects
      and tumorigenesis.

PMID- 26220365
TI  - Clinical Outcomes of Left Subclavian Artery Coverage on Morbidity and Mortality
      During Thoracic Endovascular Aortic Repair for Distal Arch Aneurysms.
AB  - BACKGROUND: This single-center study assessed left subclavian artery (LSA)
      revascularization management and morbidity and mortality of LSA coverage outcomes
      during elective thoracic endovascular aortic repair (TEVAR) for distal arch
      aneurysms. METHODS: Between July 2006 and June 2014, 178 patients underwent TEVAR
      (zone 2 + 3) for distal arch aneurysms. TEVAR with LSA coverage (zone 2) was
      performed in 121 patients (68.0 %). Multivariate analysis was performed to
      determine factors associated with perioperative cerebral infarction (CI) and
      postoperative endoleak (EL). RESULTS: Technical success was achieved in 96.7 %.
      LSA coil embolization was performed in 72.7 %. Subclavian artery crossover bypass
      was required in 9.1 %. Perioperative complications were CI (6.6 %) and paraplegia
      (1.7 %). The 30-day mortality rate was 2.5 % (n = 3). There were significant
      differences by CI univariate analysis in coverage range (>=300 mm) (P = 0.003)
      and shaggy aorta (P = 0.044). Primary EL occurred in 14.0 % (n = 17). We found
      statistically significant difference of primary EL in chronic obstructive
      pulmonary disease (P = 0.016), preoperative aneurysm diameter (P = 0.041), and
      proximal stent graft diameter (P = 0.029). Left upper extremity symptoms
      developed in 5.8 % (n = 7); vertebrobasilar insufficiency occurred in 4.1 % (n =
      5). Freedom from secondary intervention rates after 1, 3, and 5 years were 96.1,
      78.3, and 63.4 %, respectively. CONCLUSIONS: Our mid- to long-term results of
      TEVAR with LSA coverage were generally acceptable. Routine revascularization was
      not necessary in majority of zone 2 TEVAR. CI occurred in approximately 6 % of
      the cases, secondary interventions were performed more often for ELs.

PMID- 26220364
TI  - Depressive symptoms predict non-completion of a structured exercise intervention
      for people with Type 2 diabetes.
AB  - AIM: To quantify the impact of depressive symptoms on completion of exercise
      based rehabilitation for Type 2 diabetes management. METHODS: Depressive symptoms
      were assessed using the Center for Epidemiological Studies Depression scale in a
      prospective cohort of consecutive patients with Type 2 diabetes entering a 6
      month hybrid (home- and clinic-based) exercise rehabilitation programme.
      Attendance at exercise sessions was monitored and programme completion/non
      completion was ascertained. RESULTS: Of the programme participants (n=624, mean
      age 55.6+/-10.5 years, 47% male), 26.8% endorsed significant depressive symptoms
      (depression score >=16) and 68.1% completed the intervention, attending 54.6+/
      30.0% of supervised exercise sessions. Baseline depressive symptoms (depression
      scale score >=16) increased the risk of non-completion [hazard ratio 1.49 (95% CI
      1.10-2.03); P = 0.010], and predicted fewer sessions attended (beta=-2.1, P=
      0.002) in adjusted models. A depression score threshold of >=10 (48.4% of
      participants) predicted non-completion [hazard ratio 1.60 (95% CI 1.19-2.17); P=
      0.002) with optimum accuracy. Non-completions resulting from lack of interest
      (18.9 vs. 11.0%; P= 0.026) and medical complications (14.6 vs. 6.6%; P= 0.006)
      were more common among participants with depression scores >=10. Greater hazard
      ratios for depression scores >=10 were observed in subgroups not currently using
      insulin [hazard ratio 1.70 (95% CI 1.24-2.33); P= 0.001), or an antidepressant
      [hazard ratio 1.83 (95% CI 1.32-2.54); P<0.001]. CONCLUSIONS: Depressive symptoms
      were highly prevalent among participants with Type 2 diabetes entering exercise
      based rehabilitation, and even mild depressive symptoms posed a significant
      barrier to completion. Depression screening may help target additional supports
      to facilitate completion of exercise interventions for people with Type 2
      diabetes.

PMID- 26220366
TI  - Safety Evaluation of Hemoglobin-Albumin Cluster "HemoAct" as a Red Blood Cell
      Substitute.
AB  - A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core-shell
      structured hemoglobin-albumin cluster designated as "HemoAct", is an O2-carrier
      designed for use as a red blood cell (RBC) substitute. This report describes the
      blood compatibility, hemodynamic response, and pharmacokinetic properties of
      HemoAct, and then explains its preclinical safety. Viscosity and blood cell
      counting measurements revealed that HemoAct has good compatibility with whole
      blood. Intravenous administration of HemoAct into anesthetized rats elicited no
      unfavorable increase in systemic blood pressure by vasoconstriction. The half
      life of (125)I-labeled HemoAct in circulating blood is markedly longer than that
      of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded
      equivalent values to those observed in the control group with HSA.
      Histopathologic inspections of the vital organs revealed no marked abnormality in
      their tissues. All results indicate that HemoAct has sufficient preclinical
      safety as an alternative material for RBC transfusion. 

PMID- 26220367
TI  - Role of brain infarcts in behavioral variant frontotemporal dementia:
      Clinicopathological characterization in the National Alzheimer's Coordinating
      Center database.
AB  - Diagnosing behavioral variant frontotemporal dementia (bvFTD) in patients with
      prior history of stroke or with silent brain infarcts on neuroimaging studies can
      be challenging. Vascular changes in patients with bvFTD are not unusual, but
      bvFTD tends to be ruled out in the presence of cerebrovascular disease. We aimed
      to identify the clinical, cognitive, and risk factor profile of bvFTD with
      coexistent cerebrovascular disease (V-bvFTD). We compared demographic data,
      clinical diagnoses, vascular risk factors, functional status, and normalized
      neuropsychological z-scores between patients with V-bvFTD versus bvFTD without
      concomitant cerebrovascular disease (NV-bvFTD) from the National Alzheimer's
      Coordinating Centre database. We included 391 neuropathologically-diagnosed cases
      of frontotemporal lobe degeneration. We excluded patients that were diagnosed
      with aphasic variants of frontotemporal dementia before death. Patients with V
      bvFTD (n = 62) were older at the time of onset of cognitive decline (71.6 vs.
      62.5 years, p < 0.001) and death (78.7 vs. 69.6, p < 0.001), more likely to be
      hypertensive (75.8% vs. 45.7%, p = 0.002) and to have a history of stroke (21.2%
      vs. 6.1%, p = 0.007) than those with NV-bvFTD (n = 329). V-bvFTD was often
      underdiagnosed, affected elderly patients, and had a similar cognitive profile as
      NV-bvFTD despite the presence of brain infarcts. In the whole cohort, we observed
      enhanced cognitive performance with increasing age quintiles despite larger
      proportions of cerebrovascular disease pathology, likely meaning that
      frontotemporal lobe degeneration-related primary neurodegeneration exerts a
      stronger impact on cognition than cerebrovascular disease. Coexisting
      cerebrovascular disease should not preclude the diagnosis of bvFTD.

PMID- 26220368
TI  - Influence of consonant frequency on Icelandic-speaking children's speech
      acquisition.
AB  - PURPOSE: A developmental hierarchy of phonetic feature complexity has been
      proposed, suggesting that later emerging sounds have greater articulatory
      complexity than those learned earlier. The aim of this research was to explore
      this hierarchy in a relatively unexplored language, Icelandic. METHOD: Twenty
      eight typically-developing Icelandic-speaking children were tested at 2;4 and 3;4
      years. Word-initial and word-medial phonemic inventories and a phonemic
      implicational hierarchy are described. RESULT: The frequency of occurrence of
      Icelandic consonants in the speech of 2;4 and 3;4 year old children was, from
      most to least frequent, n, s, t, p, r, m, l, k, f, v, j, o, h, kh, c, [Formula:
      see text], m, ph, th, ch, c, [Formula: see text], [Formula: see text], [Formula:
      see text]. CONCLUSION: Consonant frequency was a strong predictor of consonant
      accuracy at 2;4 months (r(23) = -0.75), but the effect was weaker at 3;4 months
      (r(23) = -0.51). Acquisition of /c/, /[Formula: see text]/ and /l/ occurred
      earlier, relative to English, Swedish, Dutch and German. A frequency-bound
      practice effect on emerging consonants is proposed to account for the early
      emergence of /c/, /[Formula: see text]/ and /l/ in Icelandic.

PMID- 26220369
TI  - Predictors of Health Status in Mothers of Premature Infants with Implications for
      Clinical Practice and Future Research.
AB  - BACKGROUND: Postpartum health research has focused primarily on full-term
      mothers. AIMS: To explore postpartum stress, depression, social support, health
      status, and predictors of health status in mothers of premature infants. METHODS:
      This study employed a cross-sectional design. With convenience sampling, a total
      of 203 mothers of premature infants were recruited from two medical centers and
      four community teaching hospitals in southern Taiwan. The Hung Postpartum Stress
      Scale, Social Support Scale, Beck Depression Inventory, and Chinese Health
      Questionnaire were used to assess the mothers' psychosocial features during the
      first 6 weeks postpartum. RESULTS: Mothers' health status differed significantly
      according to levels of postpartum stress and depression. The important health
      status predictors were age, education, postpartum stress, and depression level.
      DISCUSSION: The concerns and needs of mothers of premature infants differed from
      those of full-term mothers during the first 6 weeks postpartum; premature
      infants' health status was found to be a major perceived stressor for their
      mothers. LINKING EVIDENCE TO ACTION: In the process of caring for premature
      infants' mothers, healthcare providers should provide individualized care to meet
      their needs, thus facilitating the reduction of postpartum stress and depression
      levels. During premature infants' hospitalizations, healthcare providers should
      hold regular faculty meetings to provide postpartum women with relevant
      information about their infants' health and how to best care for them. Future
      studies should explore postpartum stress, social support, depression, and health
      status each postpartum week, which could serve as a guide for nursing
      interventions.

PMID- 26220370
TI  - Offset-sparsity decomposition for automated enhancement of color microscopic
      image of stained specimen in histopathology.
AB  - We propose an offset-sparsity decomposition method for the enhancement of a color
      microscopic image of a stained specimen. The method decomposes vectorized
      spectral images into offset terms and sparse terms. A sparse term represents an
      enhanced image, and an offset term represents a "shadow." The related
      optimization problem is solved by computational improvement of the accelerated
      proximal gradient method used initially to solve the related rank-sparsity
      decomposition problem. Removal of an image-adapted color offset yields an
      enhanced image with improved colorimetric differences among the histological
      structures. This is verified by a no-reference colorfulness measure estimated
      from 35 specimens of the human liver, 1 specimen of the mouse liver stained with
      hematoxylin and eosin, 6 specimens of the mouse liver stained with Sudan III, and
      3 specimens of the human liver stained with the anti-CD34 monoclonal antibody.
      The colorimetric difference improves on average by 43.86% with a 99% confidence
      interval (CI) of [35.35%, 51.62%]. Furthermore, according to the mean opinion
      score, estimated on the basis of the evaluations of five pathologists, images
      enhanced by the proposed method exhibit an average quality improvement of 16.60%
      with a 99% CI of [10.46%, 22.73%].

PMID- 26220371
TI  - Anterior temporal lobectomy compared with laser thermal hippocampectomy for
      mesial temporal epilepsy: A threshold analysis study.
AB  - PURPOSE: Anterior Temporal Lobectomy (ATL) is the gold standard surgical
      treatment for refractory temporal lobe epilepsy (TLE), but it carries the risks
      associated with invasiveness, including cognitive and visual deficits and
      potential damage to eloquent structures. Laser thermal hippocampectomy (LTH) is a
      new procedure that offers a less invasive alternative to the standard open
      approach. In this decision analysis, we determine the seizure freedom rate at
      which LTH would be equivalent to ATL. METHODS: MEDLINE searches were performed
      for studies of ATL from 1995 to 2014. Using complication and success rates from
      the literature, we constructed a decision analysis model for treatment with ATL
      and LTH. Quality-adjusted life years (QALYs) were derived from examining patient
      preferences in similar clinical conditions. LTH data were obtained from a
      preliminary multicenter study report following patients for 6-12 months. A
      sensitivity analysis in which major parameters were systematically varied within
      their 95% CIs was used. RESULTS: 350 studies involving 25,144 cases of ATL were
      included. Outcomes of LTH were taken from a recently presented multicenter series
      of 68 cases. Over a 10-year postoperative modeling period, LTH value was 5.9668
      QALYs and ATL value was 5.8854. Sensitivity analysis revealed that probabilities
      of seizure control and late morbidity of LTH are most likely to affect outcomes
      compared to ATL. We calculated that LTH would need to stop disabling seizures
      (Engel class I) in at least 43% of cases and have fewer than 40% late
      mortality/morbidity to result in quality of life at least as good as that after
      ATL. CONCLUSIONS: This decision analysis based on early follow-up data suggests
      LTH has similar utility to ATL. These early data support LTH as a potentially
      comparable less invasive alternative to ATL in refractory TLE. LTH utility may
      remain comparable to ATL even if long-term seizure control is less than that of
      ATL. Larger prospective studies with long-term follow up will be needed to
      validate the true role of LTH in the refractory epilepsy patient population.

PMID- 26220373
TI  - Cortico-cortical evoked potentials for sites of early versus late seizure spread
      in stereoelectroencephalography.
AB  - Cortico-cortical evoked potentials offer the possibility of understanding
      connectivity within seizure networks to improve diagnosis and more accurately
      identify candidates for seizure surgery. We sought to determine if cortico
      cortical evoked potentials and post-stimulation oscillatory changes differ for
      sites of EARLY versus LATE ictal spread. 37 patients undergoing
      stereoelectroencephalography were tested using a cortico-cortical evoked
      potential paradigm. All electrodes were classified according to the speed of
      ictal spread. EARLY spread sites were matched to a LATE spread site equidistant
      from the onset zone. Root-mean-square was used to quantify evoked responses and
      post-stimulation gamma band power and coherence were extracted and compared.
      Sites of EARLY spread exhibited significantly greater evoked responses after
      stimulation across all patients (t(36)=2.973, p=0.004). Stimulation elicited
      enhanced gamma band activity at EARLY spread sites (t(36)=2.61, p=0.03, FDR
      corrected); this gamma band oscillation was highly coherent with the onset zone.
      Cortico-cortical evoked potentials and post-stimulation changes in gamma band
      activity differ between sites of EARLY versus LATE ictal spread. The oscillatory
      changes can help visualize connectivity within the seizure network. 

PMID- 26220372
TI  - Lacosamide modulates interictal spiking and high-frequency oscillations in a
      model of mesial temporal lobe epilepsy.
AB  - OBJECTIVE: Nearly one third of patients presenting with mesial temporal lobe
      epilepsy (MTLE), the most prevalent lesion-related epileptic disorder in
      adulthood, do not respond to currently available antiepileptic medications. Thus,
      there is a need to identify and characterize new antiepileptic drugs. In this
      study, we used the pilocarpine model of MTLE to establish the effects of a third
      generation drug, lacosamide (LCM), on seizures, interictal spikes and high
      frequency oscillations (HFOs, ripples: 80-200 Hz, fast ripples: 250-500 Hz).
      METHODS: Sprague-Dawley rats (250-300 g) were injected with pilocarpine to induce
      a status epilepticus (SE) that was pharmacologically terminated after 1h. Eight
      pilocarpine-treated rats were then injected with LCM (30 mg/kg, i.p.) 4h after SE
      and daily for 14 days. Eight pilocarpine-treated rats were used as controls and
      treated with saline. Three days after SE, all rats were implanted with bipolar
      electrodes in the hippocampal CA3 region, entorhinal cortex (EC), dentate gyrus
      (DG) and subiculum and EEG-video monitored from day 4 to day 14 after SE.
      RESULTS: LCM-treated animals showed lower rates of seizures (0.21 (+/- 0.11)
      seizures/day) than controls (2.6 (+/-0.57), p<0.05), and a longer latent period
      (LCM: 11 (+/- 1) days, controls: 6.25 (+/- 1), p<0.05). Rates of interictal
      spikes in LCM-treated rats were significantly lower than in controls in CA3 and
      subiculum (p<0.05). Rates of ripples and fast ripples associated with interictal
      spikes in CA3 and subiculum as well as rates of fast ripples occurring outside of
      interictal spikes in CA3 were also significantly lower in LCM-treated animals. In
      controls, interictal spikes and associated HFOs correlated to seizure clustering,
      while this was not the case for isolated HFOs. SIGNIFICANCE: Our findings show
      that early treatment with LCM has powerful anti-ictogenic properties in the
      pilocarpine model of MTLE. These effects are accompanied by decreased rates of
      interictal spikes and associated HFOs. Isolated HFOs were also modulated by LCM,
      in a manner that appeared to be unrelated to its antiictogenic effects. These
      results thus suggest that distinct mechanisms may underlie interictal-associated
      and isolated HFOs in the pilocarpine model of MTLE.

PMID- 26220374
TI  - Epileptogenesis and epileptic maturation in phosphorylation site-specific SNAP-25
      mutant mice.
AB  - Snap25(S187A/S187A) mouse is a knock-in mouse with a single amino acid
      substitution at a protein kinase C-dependent phosphorylation site of the
      synaptosomal-associated protein of 25 kDa (SNAP-25), which is a target-soluble
      NSF attachment protein receptor (t-SNARE) protein essential for neurotransmitter
      release. Snap25(S187A/S187A) mice exhibit several distinct phenotypes, including
      reductions in dopamine and serotonin release in the brain, anxiety-like behavior,
      and cognitive dysfunctions. Homozygous mice show spontaneous epileptic
      convulsions, and about 15% of the mice die around three weeks after birth. The
      remaining mice survive for almost two years and exhibit spontaneous recurrent
      seizures throughout their lifetime. Here, we conducted long-term continuous video
      electroencephalogram recording of the mice and analyzed the process of
      epileptogenesis and epileptic maturation in detail. Spikes and slow-wave
      discharges (SWDs) were observed in the cerebral cortex and thalamus before
      epileptic convulsions began. SWDs showed several properties similar to those
      observed in absence seizures including (1) lack of in the hippocampus, (2)
      movement arrest during SWDs, and (3) inhibition by ethosuximide. Multiple
      generalized seizures occurred in all homozygous mice around three weeks after
      birth. However, seizure generation stopped within several days, and a seizure
      free latent period began. Following a spike-free quiet period, the number of
      spikes increased gradually, and epileptic seizures reappeared. Subsequently,
      spontaneous seizures occurred cyclically throughout the life of the mice, and
      several progressive changes in seizure frequency, seizure duration, seizure cycle
      interval, seizure waveform, and the number and waveform of epileptic discharges
      during slow-wave sleep occurred with different time courses over 10 weeks.
      Anxiety-related behaviors appeared suddenly within three days after epileptic
      seizures began and were delayed markedly by oral administration of valproic acid.
      These results showed that Snap25(S187A/S187A) mice exhibited a variety of
      epilepsy-related phenomena, and thus, they will be useful for understanding the
      mechanisms of epileptogenesis, epileptic maturation, and the actions of
      antiepileptic drugs.

PMID- 26220376
TI  - Type 1 diabetes mellitus in people with pharmacoresistant epilepsy: Prevalence
      and clinical characteristics.
AB  - BACKGROUND: There have been inconsistent reports on the potential association
      between diabetes mellitus and epilepsy. METHODS: We examined a consecutive cohort
      of 2016 people with pharmacoresistant epilepsy admitted to a tertiary medical
      centre. RESULTS: We identified 20 individuals with type 1 diabetes mellitus
      (T1DM); a point prevalence of 9.9 (95% CI: 6.4, 15.3) cases per 1000 individuals.
      This represents a more than two-fold increase relative to published prevalence
      estimates of T1DM in the general population. The onset of T1DM preceded that of
      epilepsy in 80% of individuals, by a median of 1.5 years. Individuals with T1DM
      were significantly more likely to have cryptogenic/unknown epilepsy relative to
      those with type 2 diabetes mellitus or without diabetes (85% versus 35% and 49%,
      p=0.045). All individuals with T1DM had focal epilepsy, the majority of which
      were temporal lobe in origin, although there was no evidence that this proportion
      was any different from those without T1DM (p>0.999). CONCLUSIONS: The prevalence
      of T1DM appears to be increased in people with pharmacoresistant epilepsy and is
      associated with cryptogenic/unknown epilepsy. These findings may have
      pathophysiological implications, especially in the context of anti-glutamic acid
      decarboxylase antibodies.

PMID- 26220375
TI  - Effects of site-specific infusions of methionine sulfoximine on the temporal
      progression of seizures in a rat model of mesial temporal lobe epilepsy.
AB  - Glutamine synthetase (GS) in astrocytes is critical for metabolism of glutamate
      and ammonia in the brain, and perturbations in the anatomical distribution and
      activity of the enzyme are likely to adversely affect synaptic transmission. GS
      is deficient in discrete regions of the hippocampal formation in patients with
      mesial temporal lobe epilepsy (MTLE), a disorder characterized by brain glutamate
      excess and recurrent seizures. To investigate the role of site-specific
      inhibition of GS in MTLE, we chronically infused the GS inhibitor methionine
      sulfoximine (MSO) into one of the following areas of adult laboratory rats: (1)
      the angular bundle, n=6; (2) the deep entorhinal cortex (EC), n=7; (3) the
      stratum lacunosum-moleculare of CA1, n=7; (4) the molecular layer of the
      subiculum, n=10; (5) the hilus of the dentate gyrus, n=6; and (6) the lateral
      ventricle, n=6. Twelve animals were infused with phosphate buffered saline (PBS)
      into the same areas to serve as controls. All infusions were unilateral, and
      animals were monitored by continuous video-intracranial EEG recordings for 3
      weeks to capture seizure activity. All animals infused with MSO into the
      entorhinal-hippocampal area exhibited recurrent seizures that were particularly
      frequent during the first 3 days of infusion and that continued to recur for the
      entire 3 week recording period. Only a fraction of animals infused with MSO into
      the lateral ventricle had recurrent seizures, which occurred at a lower frequency
      compared with the other MSO infused group. Infusion of MSO into the hilus of the
      dentate gyrus resulted in the highest total number of seizures over the 3-week
      recording period. Infusion of MSO into all brain regions studied, with the
      exception of the lateral ventricle, led to a change in the composition of seizure
      severity over time. Low-grade (stages 1-3) seizures were more prevalent early
      during infusion, while severe (stages 4-5) seizures were more prevalent later.
      Thus, the site of GS inhibition within the brain determines the pattern and
      temporal evolution of recurrent seizures in the MSO model of MTLE. 

PMID- 26220377
TI  - EEG characteristics predict subsequent epilepsy in children with their first
      unprovoked seizure.
AB  - One of the most important risk factors for seizure recurrence is the
      electroencephalogram (EEG) characteristics of children with a first unprovoked
      seizure. However, the nature of the relationship between the risk factors for
      subsequent epilepsy and EEG characteristics, especially the localization of EEG
      paroxysmal abnormalities (PAs), remains unclear. The importance of EEG
      characteristics, especially the localizations of PAs, as predictors for
      subsequent epilepsy in children with a first unprovoked seizure was investigated.
      The participants were recruited from University of Yamanashi Hospital between
      July 1, 1997 and June 30, 2010 and followed until December 31, 2014. Eligible
      candidates were children between 1 month and 15 years old who presented with
      their first unprovoked non-febrile seizure. Awake and sleep EEGs were performed
      on a 12- or 16-channel machine 7-20 days after a first unprovoked seizure.
      Agreement regarding the presence of a PA was required for inclusion of the
      patient in the study. EEG PAs were classified based on the presence of spikes,
      sharp waves, or spike-wave complexes, whether focal or generalized, that were
      considered abnormal for age and state. All subjects were followed for more than 4
      years. Of 87 subjects, 48 (55.2%) experienced recurrence. On the other hand, of
      87 subjects, 52 (59.8%) showed an EEG PA. Of 18 patients with paroxysms in the
      frontal region, 17 (94.4%) developed epilepsy. Patients with frontal EEG
      paroxysms had a significantly higher risk of developing epilepsy than those with
      focal paroxysms in other regions of EEG foci (p<0.05). Moreover, compared with
      generalized EEG foci, the odds ratios for patients with frontal, RD, occipital,
      and mid-temporal EEG foci were 85.0 (95% CI: 4.5-1617.1), 9.3 (0.9-96.0), 2.5
      (0.1-62.6), and 7.5 (0.5-122.7), respectively. Children with a first unprovoked
      seizure presenting with frontal paroxysmal EEG abnormalities may be at risk for
      the development of epilepsy later in life. 

PMID- 26220378
TI  - Incidence and risk of seizures in Alzheimer's disease: A nationwide population
      based cohort study.
AB  - The reported incidence and risk factors mediating seizures in Alzheimer's disease
      (AD) have been extremely inconsistent and relevant data is lacking in Asia. We
      investigated the incidence rate and risk of seizures in AD and in a large,
      nationwide cohort from Han Chinese. A retrospective population-based study was
      conducted on the data from Taiwan's National Health Insurance Research Database
      from 2000 to 2010. To reduce selection bias, we applied propensity scores,
      wherein 981 patients with AD were matched to 3835 non-AD controls from a pool of
      1000,000 randomly sampled cohort dataset. This approach was based on age, sex,
      comorbidities and previous brain conditions. Incidence rate, cumulative incidence
      and hazard ratios (HRs) were estimated. During the 10-year follow-up period (mean
      follow-up time, 4.02 years), 44 out of 937 AD patients (4.7%) developed seizures.
      The incidence rate in the AD cohort (11.9 per 1000 person-years) was higher than
      that in the matched cohort (5.7 per 1000 person-years), with an adjusted HR of
      1.85 (95% confidence interval [CI], 1.20-2.83, p=0.005). The mean duration from
      the diagnosis of AD to the occurrence of seizure is 3.6 years. The Cox regression
      analysis revealed that AD itself is a significant predictor after adjustment for
      confounders (HR=2.01, 95% CI, 1.40-2.90, p<0.001). Moreover, age is an
      independent predictor, with an adjusted HR of 1.03 (95% CI, 1.00-1.05, p=0.019).
      In conclusion, seizure occurrence in AD is more common than in the matched
      cohort. Notably, advanced age carries a higher risk for development of seizures
      in patients with AD. 

PMID- 26220379
TI  - Validation of the 6 Hz refractory seizure mouse model for
      intracerebroventricularly administered compounds.
AB  - The six hertz (6 Hz) refractory seizure model is considered an indispensable
      chain of the Anticonvulsant Screening Project. We here describe an adapted
      protocol using the intracerebroventricular (i.c.v.) delivery route, which will
      allow researchers to perform targetvalidation or proof-of-principle studies using
      promising compounds with unknown or limited blood-brain barrier permeability
      (e.g. neuropeptides and peptidomimetics) in this model. Seizures were induced by
      single application of a current intensity of 49 mA to i.c.v.-implanted NMRI mice
      using an ECT Unit 57800 Ugo Basile stimulator. By applying these key parameters,
      c-Fos immunohistochemistry revealed the recruitment of the dentate gyrus,
      ratifying this model as a valuable tool for testing i.c.v. administered compounds
      against therapy-resistant seizures. This finding was further strengthened, since
      i.c.v. administration of levetiracetam suppressed 6 Hz-evoked seizure severity
      but sodium phenytoin did not. We also propose to use "seizure duration" as an
      alternative, accurate parameter to express the results within this model.

PMID- 26220380
TI  - Effects of eugenol on granule cell dispersion in a mouse model of temporal lobe
      epilepsy.
AB  - Granule cell dispersion (GCD), a structural abnormality, is characteristic of
      temporal lobe epilepsy (TLE). Eugenol (EUG) is an essential component of
      medicinal herbs and is suggested to exert anticonvulsant activity. However, it is
      unclear whether EUG ameliorates the abnormal morphological changes in granule
      cells induced by epileptic insults. In the present study, we examined whether
      intraperitoneal injection of EUG attenuated increased seizure activity and GCD
      following intrahippocampal injection of kainic acid (KA). Our results showed that
      EUG significantly increased the seizure threshold, resulting in delayed seizure
      onset, and reduced GCD in KA-induced epilepsy. Moreover, EUG treatment
      significantly attenuated KA-induced activation of mammalian target of rapamycin
      complex 1 (mTORC1), which is involved in GCD development, in the dentate gyrus
      (DG). These results suggest that EUG may have beneficial effects in the treatment
      of epilepsy through its ability to inhibit GCD via suppression of KA-induced
      mTORC1 activation in the hippocampal DG in vivo. 

PMID- 26220381
TI  - Temporal seizure focus and status epilepticus are associated with high-sensitive
      troponin I elevation after epileptic seizures.
AB  - OBJECTIVE: Postictal elevation of high-sensitive troponin I (TNI), a highly
      specific biomarker for myocardial ischemia, has been reported. We aimed at
      evaluating its association of high-sensitive troponin I (TNI) with seizure type
      and focus, as well as vascular risk factors. METHODS: TNI was measured in 247
      patients admitted to our clinic via the emergency room with an acute epileptic
      seizure. TNI control measurements were performed in 61.5% of cases. All patients
      underwent electroencephalography and cerebral imaging. Seizure focus - when
      possible - was determined using results from these examinations as well as
      clinical data. RESULTS: Of 247 patients, 133 (53.8%) were men, the mean age was
      59 +/- 18 years. 70 (28.3%) patients had focal and 177 (71.7%) generalized
      seizures. Status epilepticus was present in 38 cases (15.4%). Mean TNI was 0.05
      +/- 0.17. TNI was elevated in 27 patients (10.9%). Higher age, status epilepticus
      and temporal seizure focus were significantly associated with TNI elevation in
      multivariate analysis. In 21 (13.8%) of the patients with TNI control
      measurement, TNI was continuously elevated. Higher age and temporal seizure focus
      were significantly associated with continuously high TNI. Coronary heart disease
      and vascular risk factors were significantly associated with high TNI only in
      univariate analysis. No patient had a symptomatic myocardial ischemia.
      DISCUSSION: Postictal TNI elevation is relatively common in older patients with
      status epilepticus or temporal seizure focus. These data support the concept of
      relevant and possibly dangerous ictal effects on cardiac function especially in
      temporal lobe seizures. Although the risk of manifest postictal myocardial
      infarction seems to be very low, selected patients could profit from closer
      monitoring.

PMID- 26220382
TI  - Localization value of seizure semiology analyzed by the conditional inference
      tree method.
AB  - OBJECTIVE: Although accurate interpretation of seizures is important for the
      management of patients with epilepsy, studies on the localizing value of seizure
      semiology and the reliability of the semiology descriptions are scarce. The
      objective of our study is to investigate the accuracy of video-recorded seizure
      semiology in the classification and localization of epileptic seizures. We also
      evaluated the reliability of the semiology descriptions provided by the patients
      or their caregivers. METHODS: Video-recorded clinical seizures from 831
      consecutive patients (391 females; 31.7 +/- 11.6 years) were analyzed
      retrospectively. Epileptic seizures were classified as generalized and partial
      seizures, and patients with partial seizures were further divided into five ictal
      onset areas. In order to analyze the diagnostic value of individual semiologic
      features for clinical diagnosis, we used the conditional inference tree method.
      RESULTS: Generalized and partial seizures were differentiated with high accuracy
      (97.1%), but the accuracy of localization among the five ictal onset areas was
      relatively low (56.1%), which was largely attributed to the difficulty in the
      discrimination between mesial and lateral temporal onset seizures. Lateralization
      of the ictal onset area in partial seizures was possible in 427 (55.1%) patients
      based on video analysis, nevertheless it was possible in only 158 (20.4%)
      patients based on historical semiology descriptions. CONCLUSIONS: The results of
      our study suggest that careful observation of seizure semiology may be useful for
      the differentiation of ictal onset areas. However, the semiologic differentiation
      between mesial and lateral temporal onset seizures is difficult, and historical
      semiologic descriptions should be interpreted carefully because of their low
      reliability.

PMID- 26220383
TI  - GWAS identifies two susceptibility loci for lamotrigine-induced skin rash in
      patients with epilepsy.
AB  - PURPOSE: Lamotrigine (LTG)-induced maculopapular eruption (MPE) often causes
      treatment discontinuation and rising burdens on current healthcare systems. We
      conducted a genome-wide association study to identify novel susceptibility loci
      associated with LTG-induced MPE in patients with epilepsy. MATERIALS AND METHODS:
      We enrolled patients with LTG-induced MPE (n=34) and utilized the Korea
      Association Resource project cohort as a control group (n=1214). We explored
      associations between LTG-induced MPE and single nucleotide polymorphisms (SNPs)
      through imputation and replicated these associations in samples from 59 LTG
      induced MPE cases and 98 LTG tolerant-controls. RESULTS: We found two novel SNPs
      associated with LTG-induced MPE: rs12668095 near CRAMP1L/TMEM204/IFT140/HN1L
      (P=4.89*10(-7)) and rs79007183 near TNS3 (P=3.15*10(-10)), both of which were
      replicated in an independent cohort. CONCLUSION: These two validated SNPs may be
      good candidate markers for predicting LTG-induced MPE in epilepsy patients,
      although further experimental validation is needed.

PMID- 26220385
TI  - ABCB1 G2677T/A polymorphism is associated with the risk of drug-resistant
      epilepsy in Asians.
AB  - Pharmacogenetic factors may play an important role in drug-resistant epilepsy.
      The association between the non-synonymous polymorphism G2677T/A in the coding
      region of the ABCB1 gene, and the risk of resistance to anti-epileptic drugs
      (AEDs) in epilepsy remains controversial. The present study used a meta-analysis
      approach to assess the pooled association between this polymorphism and the risk
      of resistance to AEDs. We used several online libraries to identify suitable
      studies published before September 2014, and 15 studies (n=1773 drug-resistant,
      and n=2250 drug-responsive epilepsy cases) were selected for our analysis. Pooled
      odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the
      strength of the association. Subgroup analysis was performed taking into account
      different ethnic groups. Our results suggest that ethnicity plays a role in the
      association between ABCB1 G2677T/A polymorphism and drug-resistant epilepsy. We
      found a significant association for Asians both under the codominant model TT vs.
      GG (OR=1.33, 95% CI: 1.05-1.69; P=0.019), and the allele model T vs. G (OR=1.13,
      95% CI: 1.01-1.27; P=0.032). However, no association was observed for Caucasians
      in either the TT vs. GG (OR=0.85, 95% CI: 0.61-1.18; P=0.335), or the T vs. G
      (OR=0.93, 95% CI: 0.78-1.09; P=0.362) models. A cumulative meta-analysis showed
      that these results were robust. In conclusion, our analysis indicates that ABCB1
      G2677T/A polymorphism may increase the risk of drug-resistant epilepsy in Asians.

PMID- 26220386
TI  - Decreased expression of hippocampal Na+/Ca2+ exchanger isoform-1 by
      pentylenetetrazole kindling in mice.
AB  - Previous studies have shown that inhibitors of the Na(+)/Ca(2+) exchanger (NCX)
      attenuate seizure activity in drug-induced epilepsy models, but the role of NCX
      in epilepsy is not fully understood. The present study examined the effects of
      pentylenetetrazole (PTZ)-induced kindling on the mRNA expression of NCX isoforms
      (NCX1, NCX2 and NCX3) in mouse brain. Chronic administration of PTZ at 40mg/kg
      resulted in kindling seizure development. It caused decreases in the mRNA levels
      of NCX1 and NCX2, but not NCX3, in the hippocampus. Changes in NCX isoform
      expression levels were not observed in the prefrontal cortex or striatum. Acute
      PTZ at 40mg/kg, which caused little seizure activity, also decreased NCX2, but
      not NCX1 mRNA levels in the hippocampus. These results suggest that down
      regulation of hippocampal NCX1 expression is associated with PTZ-induced kindling
      seizure development.

PMID- 26220384
TI  - Investigation of GRIN2A in common epilepsy phenotypes.
AB  - Recently, mutations and deletions in the GRIN2A gene have been identified to
      predispose to benign and severe idiopathic focal epilepsies (IFE), revealing a
      higher incidence of GRIN2A alterations among the more severe phenotypes. This
      study aimed to explore the phenotypic boundaries of GRIN2A mutations by
      investigating patients with the two most common epilepsy syndromes: (i)
      idiopathic generalized epilepsy (IGE) and (ii) temporal lobe epilepsy (TLE).
      Whole exome sequencing data of 238 patients with IGE as well as Sanger sequencing
      of 84 patients with TLE were evaluated for GRIN2A sequence alterations. Two
      additional independent cohorts comprising 1469 IGE and 330 TLE patients were
      screened for structural deletions (>40kb) involving GRIN2A. Apart from a
      presumably benign, non-segregating variant in a patient with juvenile absence
      epilepsy, neither mutations nor deletions were detected in either cohort. These
      findings suggest that mutations in GRIN2A preferentially are involved in genetic
      variance of pediatric IFE and do not contribute significantly to either adult
      focal epilepsies as TLE or generalized epilepsies. 

PMID- 26220387
TI  - Autonomic changes following generalized tonic clonic seizures: An analysis of
      adult and pediatric patients with epilepsy.
AB  - OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is the most common cause
      of mortality directly related to epilepsy. Its incidence is higher in adult
      patients and its pathophysiology remains poorly understood, but likely involves
      autonomic dysregulation following generalized tonic clonic seizures (GTCS). In
      the current study, we aimed to analyze post-ictal autonomic changes following
      GTCS in adult and pediatric patients. METHODS: Patients admitted to the epilepsy
      monitoring unit were prospectively recruited, and wore an electrodermal activity
      (EDA) wrist sensor that continuously measured sympathetic activity while being
      monitored with EEG and EKG electrodes. Peri-ictal EDA parameters were assessed as
      a measure of sympathetic activity. Peri-ictal parasympathetic activity was
      determined through the high frequency component (HF) analysis of heart rate
      variability (HRV). The duration of post-ictal generalized EEG suppression (PGES)
      was also documented. RESULTS: Twenty patients with GTCS were included in the
      study on whom 30 GTCS were recorded. PGES duration strongly correlated with age
      (r=0.62, p=0.004) and measures of the EDA response. After controlling for PGES
      duration, we found pediatric patients had greater sympathetic activation measured
      as log rising portion of the area under the curve of the EDA response
      (beta=+0.67, p=0.034) and a higher degree of vagal suppression measured as
      maximal percentage change of HF power (beta=-12.65, p=0.0036). CONCLUSION:
      Sympathetic activity can be measured in the peri-ictal period, and directly
      correlates with PGES duration. Age is a significant determinant of the
      sympathetic and parasympathetic response following a GTCS; given the same PGES
      duration, pediatric patients demonstrate stronger sympathetic activation and
      higher vagal suppression. However, the increase in PGES duration with age and the
      associated autonomic dysregulation may provide clues as to why there is a
      variable vulnerability to SUDEP across age groups.

PMID- 26220388
TI  - Subjective sleep disturbance in epilepsy patients at an outpatient clinic: A
      questionnaire-based study on prevalence.
AB  - OBJECTIVE: The clinically important interaction between epilepsy and sleep is
      complex. The aim of this paper is to review the frequency of sleep complaints and
      the comorbidity of sleep disorders in people with epilepsy attending an
      outpatient clinic. METHODS: Sleep complaints and presence of sleep disorders were
      assessed by means of a standard questionnaire form composed of 132 questions in
      208 patients and 212 controls. The questionnaire includes Pittsburgh Sleep
      Quality Index, the Epworth Sleepiness Scale, the Beck Depression Scale, and the
      Berlin Questionnaire for sleep apnea. RESULTS: We showed poorer sleep quality, a
      higher frequency of subjective sleep disturbances in epilepsy patients. The major
      complaints of patients related to poor sleep quality included the symptoms of
      insomnia, sleep apnea, and parasomnias. They have higher frequency of sleep onset
      and maintenance insomnia, REM behavioral disorders, and sleep apnea. Nocturnal
      seizures (47%) and epileptiform activities on EEG (47%) were more frequent in
      patients with insomnia (p=0.02, p=0.06). Furthermore, the patients with a high
      risk of sleep apnea frequently used more than one antiepileptic drugs (AED) (41%,
      p<0.01) and the duration of epilepsy was longer in these patients (p=0.02).
      Moreover insomnia (p=0.01) was significantly lower in patients having no seizures
      in the last 2 years and the risk of apnea (p=0.04) and bad quality of sleep
      (p=0.01) was higher in patients with seizures. CONCLUSION: The results emphasize
      the extent of the comorbidity of sleep disorders and epilepsy in an outpatient
      clinic. They have higher frequency of sleep onset, maintenance insomnia, probable
      RBD, and sleep apnea than healthy controls do. The severity of epilepsy can
      increase the risk of some sleep disorders like insomnia and sleep apnea.
      Aggressive treatment of nocturnal seizures and EEG can be considered to prevent
      insomnia. On the other hand, chronicity can lead to sleep apnea and so PSG
      investigations can be routinely done in patients having video-EEG monitoring due
      to refractory epilepsy.

PMID- 26220389
TI  - Preserved anterograde and remote memory in drug-responsive temporal lobe
      epileptic patients.
AB  - PURPOSE: To investigate cognition, particularly anterograde and remote memory, in
      patients suffering from unilateral drug-responsive mesial temporal lobe epilepsy
      (mTLE) patients and to compare their performance with that observed in drug
      resistant mTLE patients. METHODS: Sixteen drug-responsive mTLE patients, with
      only infrequent seizures in their lifetime, were matched for demographic and
      clinical variables to 18 patients suffering from drug-resistant unilateral mTLE.
      A comprehensive neuropsychological examination, including baseline, anterograde
      memory tasks, and a large range of remote memory tests was carried out. RESULTS:
      Patients with drug-responsive epilepsy obtained average scores on every
      anterograde memory test. Although in general, they obtained lower scores than the
      healthy controls on remote memory tests, the differences failed to reach
      significance. Moreover, the drug-responsive group performed significantly better
      than the drug-resistant group on anterograde recall tests and an episodic
      autobiographical memory test. Performance was not significantly different between
      the patient groups in personal semantics or memory for public events. CONCLUSION:
      Our results show that a mild clinical course of mTLE with no cognitive deficits
      can occur notwithstanding hippocampal sclerosis. The differences in cognitive
      function between the two groups are likely due to distinct pathophysiology of the
      underlying cause of epilepsy. Drug-resistant seizures and cognitive deficits may
      be the consequence of a more severe underlying cerebral process. Better
      understanding of the variety of pathogenesis of mTLE could help to answer this
      open question.

PMID- 26220390
TI  - Scalp high frequency oscillations (HFOs) in absence epilepsy: An independent
      component analysis (ICA) based approach.
AB  - BACKGROUND: High frequency oscillations (HFOs) have provided a new insight in
      understanding ictogenesis and seizure localization. In absence seizures, HFOs
      were predominantly localized in the medial prefrontal cortex (MPFC) in MEG
      studies. METHODS: We studied HFOs (80-250 Hz) in scalp EEGs in patients with
      absence epilepsy, and evaluated their frequency bandwidth and spatial-temporal
      distribution. EEG of 9 patients with absence epilepsy (CAE:JAE-8:1; M:F=7:2; age:
      8.1 +/- 2.1 years; age at onset: 6.6 +/- 1.3 years) were evaluated with scalp EEG
      (sampling rate: 2048 Hz). Finite impulse response filters on the unipolar or
      longitudinal bipolar montages were band-passed between 80 and 250 Hz using
      Cartool((r)) and EEGLAB((r)). Sensitivity and paper speed were modified
      accordingly to study the HFOs. Thousand four hundred and thirty eight artifact
      free 'spike-wave' epileptiform discharges were analyzed. Sleep ictal SW
      discharges, defined as runs of 3 Hz GSWDs lasting >= 4s in stages 1 and 2 sleep,
      were analyzed by independent component analysis and component time-frequency and
      channel time-frequency maps using cyclical tapering wavelet transform. A total of
      926 HFOs were identified of 1438 GSWDS. RESULTS: The HFOs were associated with
      inter-ictal generalized spike-wave discharges (IiGSWDs-241/454), ictal GSWDs
      (IcGSWD-634/884), sporadic SWDs (sSWDs-51/100). The percentage of HFOs was higher
      in IcGSWD when compared to both IiGSWDs and sporadic SWDs together
      (chi(2)=52.864, d.o.f=1, p<0.0001). The mean frequency of HFOs was 96.4 +/- 10.4
      Hz. A channel wise analysis showed the maximum HFO band width in the right fronto
      central region (F4=28 Hz, C4=24 Hz). CONCLUSION: Narrow bandwidth interictal and
      ictal HFOs can be identified in scalp EEG of patients with absence epilepsy.
      Further characterization of the various properties of pHFOs will be helpful in
      opening up a domain of clinical evaluation and interpretation of the various
      epileptic disorders. To improve the insights into the onset and spread of absence
      seizures, and to study the network properties, one could analyze the HFOs in high
      density EEG arrays with multimodal integration using MEG or fMRI.

PMID- 26220391
TI  - Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence
      epilepsy.
AB  - BACKGROUND: De novo SCN8A missense mutations have been identified as a rare
      dominant cause of epileptic encephalopathy. We described a person with epileptic
      encephalopathy associated with a mosaic deletion of the SCN8A gene. METHODS:
      Array comparative genome hybridization was used to identify chromosomal
      abnormalities. Next Generation Sequencing was used to screen for variants in
      known and candidate epilepsy genes. A single nucleotide polymorphism array was
      used to test whether the SCN8A variants were in cis or in trans. RESULTS: We
      identified a de novo mosaic deletion of exons 2-14 of SCN8A, and a rare
      maternally inherited missense variant on the other allele in a woman presenting
      with absence seizures, challenging behavior, intellectual disability and QRS
      fragmentation on the ECG. We also found a variant in SCN5A. CONCLUSIONS: The
      combination of a rare missense variant with a de novo mosaic deletion of a large
      part of the SCN8A gene suggests that other possible mechanisms for SCN8A
      mutations may cause epilepsy; loss of function, genetic modifiers and cellular
      interference may play a role. This case expands the phenotype associated with
      SCN8A mutations, with absence epilepsy and regression in language and memory
      skills.

PMID- 26220392
TI  - Response to "Association of IDH1/2 mutation with preoperative seizure in low
      grade gliomas: How strong is the evidence?".

PMID- 26220393
TI  - Assessing long-term effects of eslicarbazepine acetate on lipid metabolism
      profile, sodium values and liver function tests.
AB  - INTRODUCTION: Older dibenzazepines with a carboxamide substitution have been
      demonstrated to cause deleterious effects on lipid metabolism profile, as well as
      frequent hyponatremia. The aim of our study is to assess the effects of
      eslicarbazepine acetate, a novel AED, on lipid metabolism profile, sodium values
      and liver function tests, as well as to compare them with previous effects of
      carbamazepine and oxcarbazepine. METHODS: This report describes a retrospective
      cohort study of 108 patients who were treated with eslicarbazepine. Of these
      patients, 52% had switched to eslicarbazepine from prior treatment with
      carbamazepine or oxcarbazepine. Laboratory values concerning lipid metabolism
      profile, liver function tests and sodium were assessed before and after
      beginning/switching treatment. Patients who began treatment or whose treatment
      for dyslipidemia was modified during the study period were excluded from the
      analysis. Co-medications that could impact lipid metabolism profile, sodium or
      hepatic function were kept stable during the study period. RESULTS: The mean
      total cholesterol of the entire group decreased significantly from prior
      pathological to normal values after beginning/switching treatment. The percentage
      of patients with pathological values decreased. Patients switching from prior
      carboxamides also showed significant reductions in mean LDL and triglycerides.
      Patients beginning treatment without prior carboxamides did not develop
      dyslipidemia after titration. A tendency for an increased percentage of patients
      with hyponatremia was detected in both groups. CONCLUSIONS: Compared with older
      carboxamides, eslicarbazepine acetate exhibits a safer profile related to lipid
      metabolism. No relevant changes were detected in liver function tests.
      Consequently, a vascular risk factor could be avoided in patients with chronic
      epilepsy, while hyponatremia still needs to be ruled out. Prospective studies are
      still needed.

PMID- 26220394
TI  - Seizure semiology in males with psychogenic nonepileptic seizures is associated
      with somatic complaints.
AB  - AIMS: Psychopathology has been studied in patients with epileptic or psychogenic
      non-epileptic seizures in the context of diagnosis and treatment. Unfortunately,
      most PNES studies include few males and do not consider possible gender
      differences, making findings less generalizable to males with PNES. In this study
      we specifically compare males with PNES to females with PNES and to males with
      epilepsy. METHODS: Males with PNES (n=58), males with epilepsy (n=86), females
      with PNES (n=147), and females with ES (n=142) were evaluated on an inpatient
      epilepsy monitoring unit. Self-reported objective measures of psychopathology,
      demographics, and PNES seizure semiology were compared. RESULTS: Personality
      Assessment Inventory profiles revealed marked differences, particularly in
      somatic symptoms, between PNES and epilepsy. Females with PNES had higher levels
      of physiological depressive symptoms but lower antisocial features. Males with
      PNES who had clinically significant elevations on the somatic complaints scale
      were much more likely to have motor seizures while females with PNES classified
      similarly were equally likely to have either motor or non-motor events.
      CONCLUSION: Gender difference in PNES seizure semiology was associated with
      whether or not clinically significant somatic symptoms were present; males with
      elevated somatic symptoms were much more likely to have motor PNES. However, we
      did not find evidence of greater psychopathology in males with PNES compared to
      females with PNES. Gender differences in the behavioral manifestation of PNES in
      the context of presence or absence of somatization may have implications for
      diagnosis and treatment.

PMID- 26220395
TI  - Long noncoding RNAs in TDP-43 and FUS/TLS-related frontotemporal lobar
      degeneration (FTLD).
AB  - Frontotemporal lobar degeneration (FTLD) defines a spectrum of heterogeneous
      neurodegenerative disorders characterized by the progressive deterioration of the
      frontal and anterior temporal lobes of the brain. FTLD is histopathologically
      classified according to the presence of neuropathological protein aggregates. Two
      of the major pathologies, FTLD-TDP and FTLD-FUS, are characterized by the
      abnormal accumulation in cytoplasmic inclusions of RNA-binding proteins (RBPs) -
      TDP-43 and FUS/TLS, respectively. That suggests that a crucial common downstream
      pathway leading to cell death might involve the disruption of RNA-based
      mechanisms. Long noncoding RNAs have emerged as key regulators in the different
      layers of gene regulation. Increasing evidence suggests that long non-coding RNAs
      (lncRNAs) may have pivotal biological functions in the brain and, not
      surprisingly, they have been implicated with neurodegenerative diseases, like
      Alzheimer's and Parkinson's diseases. Recent studies report that FTLD/ALS-related
      proteins TDP-43 and FUS/TLS bind lncRNAs, and that several lncRNAs have binding
      sites for TDP-43 and/or FUS/TLS. These findings raise important questions about
      how TDP-43 and FUS/TLS pathologies can affect lncRNA-based mechanisms. One
      alternative is that TDP-43 and FUS/TLS regulate lncRNA transcription or
      transcript stability. In fact, it has been demonstrated that lncRNAs are
      dysregulated upon either depletion or unavailability of functional TDP-43 or
      FUS/TLS in a range of different models and diseases, including post-mortem
      samples from subjects with FTLD-TDP. The second alternative is that the binding
      to TDP-43 or FUS/TLS would enable lncRNAs to perform their cellular function. In
      this case, the unavailability of these RBPs would disrupt functional properties
      of lncRNAs, without necessarily altering their cellular levels. It has been
      experimentally demonstrated that the cellular function of some lncRNAs is
      strictly dependent on the direct binding to TDP-43 or FUS/TLS. 

PMID- 26220396
TI  - Super-mini percutaneous nephrolithotomy (SMP): a new concept in technique and
      instrumentation.
AB  - OBJECTIVE: To present a novel miniature endoscopic system designed to improve the
      safety and efficacy of percutaneous nephrolithotomy, named the 'super-mini
      percutaneous nephrolithotomy' (SMP). PATIENTS AND METHODS: The endoscopic system
      consists of a 7-F nephroscope with enhanced irrigation and a modified 10-14 F
      access sheath with a suction-evacuation function. This system was tested in
      patients with renal stones of <2.5 cm, in a multicentre prospective non
      randomised clinical trial. In all, 146 patients were accrued in 14 centres.
      Nephrostomy tract dilatation was carried out to 10-14 F. The lithotripsy was
      performed using either a Holmium laser or pneumatic lithotripter. A nephrostomy
      tube or JJ stent was placed only if clinically indicated. RESULTS: SMP was
      completed successfully in 141 of 146 patients. Five patients required conversion
      to larger nephrostomy tracts. The mean (sd) stone size was 2.2 (0.6) cm and the
      mean operative duration was 45.6 min. The initial stone-free rate (SFR) was
      90.1%. The SFR at the 3-month follow-up was 95.8%. Three patients required
      auxiliary procedures for residual stones. Complications occurred in 12.8% of the
      patients, all of which were Clavien grade <=II and no transfusions were needed.
      In all, 72.3% of the patients did not require any kind of catheter, while 19.8%
      had JJ stents and 5.7% had nephrostomy tubes placed. The mean hospital stay was
      2.1 days. CONCLUSIONS: SMP is a safe and effective treatment for renal stones of
      <2.5 cm. SMP may be particularly suitable for patients with lower pole stones and
      stones that ae not amenable to retrograde intrarenal surgery.

PMID- 26220397
TI  - Parvoviral myocarditis in a 5-week-old Dachshund.
AB  - OBJECTIVE: To describe a case of myocarditis associated with naturally occurring
      canine parvovirus type 2 (CPV-2). CASE SUMMARY: A 5-week-old male intact
      Dachshund dog presented for acute respiratory distress. Limited diagnostic tests
      prior to the dog experiencing cardiopulmonary arrest included a lateral thoracic
      radiograph, which indicated cardiomegaly and diffuse unstructured pulmonary
      infiltrate. Necropsy was performed and results identified a lymphoplasmacytic
      myocarditis with positive CPV-2 immunohistochemistry within the myocardium.
      UNIQUE INFORMATION PROVIDED: This report describes the natural occurrence of CPV
      2-associated myocarditis. In addition to highlighting this rare form of canine
      parvovirus, cardiomyopathy in survivors of the acute viral myocarditis phase is
      reviewed.

PMID- 26220398
TI  - Cryopreserved CD90+ cells obtained from mobilized peripheral blood in sheep: a
      new source of mesenchymal stem cells for preclinical applications.
AB  - Mobilized peripheral blood (MPB) bone marrow cells possess the potential to
      differentiate into a variety of mesenchymal tissue types and offer a source of
      easy access for obtaining stem cells for the development of experimental models
      with applications in tissue engineering. In the present work, we aimed to isolate
      by magnetic activated cell sorting CD90+ cells from MPB by means of the
      administration of Granulocyte-Colony Stimulating Factor and to evaluate cell
      proliferation capacity, after thawing of the in vitro culture of this population
      of mesenchymal stem cells (MSCs) in sheep. We obtained a median of 8.2 +/- 0.6
      million of CD90+ cells from the 20-mL MPB sample. After thawing, at day 15 under
      in vitro culture, the mean CD90+ cells determined by flow cytometry was 92.92 +/-
      1.29 % and cell duplication time determined by crystal violet staining was 47.59
      h. This study describes for the first time the isolation, characterization, and
      post-in vitro culture thawing of CD90+ MSCs from mobilized peripheral blood in
      sheep. This population can be considered as a source of MSCs for experimental
      models in tissue engineering research.

PMID- 26220399
TI  - Hydroxyproline Ring Pucker Causes Frustration of Helix Parameters in the Collagen
      Triple Helix.
AB  - Collagens, the most abundant proteins in mammals, are defined by their triple
      helical structures and distinctive Gly-Xaa-Yaa repeating sequence, where Xaa is
      often proline and Yaa, hydroxyproline (Hyp/O). It is known that hydroxyproline in
      the Yaa position stabilises the triple helix, and that lack of proline
      hydroxylation in vivo leads to dysfunctional collagen extracellular matrix
      assembly, due to a range of factors such as a change in hydration properties. In
      addition, we note that in model peptides, when Yaa is unmodified proline, the Xaa
      proline has a strong propensity to adopt an endo ring conformation, whilst when
      Yaa is hydroxyproline, the Xaa proline adopts a range of endo and exo
      conformations. Here we use a combination of solid-state NMR spectroscopy and
      potential energy landscape modelling of synthetic triple-helical collagen
      peptides to understand this effect. We show that hydroxylation of the Yaa proline
      causes the Xaa proline ring conformation to become metastable, which in turn
      confers flexibility on the triple helix. 

PMID- 26220400
TI  - Barefoot vs common footwear: A systematic review of the kinematic, kinetic and
      muscle activity differences during walking.
AB  - Habitual footwear use has been reported to influence foot structure with an acute
      exposure being shown to alter foot position and mechanics. The foot is highly
      specialised thus these changes in structure/position could influence
      functionality. This review aims to investigate the effect of footwear on gait,
      specifically focussing on studies that have assessed kinematics, kinetics and
      muscle activity between walking barefoot and in common footwear. In line with
      PRISMA and published guidelines, a literature search was completed across six
      databases comprising Medline, EMBASE, Scopus, AMED, Cochrane Library and Web of
      Science. Fifteen of 466 articles met the predetermined inclusion criteria and
      were included in the review. All articles were assessed for methodological
      quality using a modified assessment tool based on the STROBE statement for
      reporting observational studies and the CASP appraisal tool. Walking barefoot
      enables increased forefoot spreading under load and habitual barefoot walkers
      have anatomically wider feet. Spatial-temporal differences including, reduced
      step/stride length and increased cadence, are observed when barefoot. Flatter
      foot placement, increased knee flexion and a reduced peak vertical ground
      reaction force at initial contact are also reported. Habitual barefoot walkers
      exhibit lower peak plantar pressures and pressure impulses, whereas peak plantar
      pressures are increased in the habitually shod wearer walking barefoot. Footwear
      particularly affects the kinematics and kinetics of gait acutely and chronically.
      Little research has been completed in older age populations (50+ years) and thus
      further research is required to better understand the effect of footwear on
      walking across the lifespan. 

PMID- 26220401
TI  - A core/shell/satellite anticancer platform for 808 NIR light-driven multimodal
      imaging and combined chemo-/photothermal therapy.
AB  - In this contribution, a novel multifunctional anti-cancer nanoplatform has been
      firstly constructed by conjugating a photothermal agent (CuS nanoparticles) and a
      cancer cell target agent (folic acid, FA) onto the surface of mesoporous silica
      coated core-shell-shell up-conversion nanoparticles (UCNPs). It was found that
      the doxorubicin (DOX) loaded system exhibits obvious pH and NIR-responsive
      release behaviour and the drug can be targetedly delivered to the cancer cells by
      a receptor mediated endocytosis manner. Furthermore, both photothermal therapy
      (PTT) and chemotherapy can be triggered simultaneously by a single 808 nm near
      infrared (NIR) light source, thus leading to a synergistic effect. The combined
      chemo- and NIR photothermal therapy can significantly improve the therapeutic
      efficacy compared to any single therapy, which has been evidenced by both in
      vitro and in vivo results. Besides, due to the doped rare earth ions, the
      platform also exhibits good up-conversion luminescence (UCL), computed tomography
      (CT) and magnetic resonance imaging (MRI) properties. Based on the excellent
      multimodal imaging and anti-tumor properties, the multifunctional nanoplatform
      should be a promising candidate for imaging-guided anti-cancer therapy. 

PMID- 26220402
TI  - Negative visuospatial priming in isolation-reared rats: Evidence of resistance to
      the disruptive effects of amphetamine.
AB  - Negative visuospatial priming (NP) represents a quantifiable measure of
      inhibitory information processing that is disrupted in several neurodevelopmental
      and psychiatric disorders, including schizophrenia. We developed a novel rodent
      NP task to investigate mechanisms underlying NP and its role in various
      disorders, and to test potential therapeutics. In the present studies, we further
      characterized this novel paradigm by investigating whether NP is disrupted in
      rats reared in isolation, a developmental manipulation that produces a range of
      abnormalities in behavior, neurochemistry, and brain structure that mirror
      aspects of schizophrenia pathology. We also further explored the role of
      monoaminergic signaling in NP and the effects of isolation rearing by challenging
      both socially reared and isolation-reared rats with D-amphetamine during the NP
      task. Although fewer isolation-reared animals learned the complex NP task, those
      that learned exhibited unaffected NP compared with socially reared rats.
      Consistent with previous reports, D-amphetamine impaired NP and increased motor
      impulsivity in socially reared rats. In contrast, D-amphetamine did not affect NP
      or motor impulsivity in isolation-reared rats. These data confirm a monoaminergic
      influence on NP behavior and indicate that rats reared in isolation have altered
      dopaminergic sensitivity. 

PMID- 26220403
TI  - 14-3-3zeta coordinates adipogenesis of visceral fat.
AB  - The proteins that coordinate complex adipogenic transcriptional networks are
      poorly understood. 14-3-3zeta is a molecular adaptor protein that regulates
      insulin signalling and transcription factor networks. Here we report that 14-3
      3zeta-knockout mice are strikingly lean from birth with specific reductions in
      visceral fat depots. Conversely, transgenic 14-3-3zeta overexpression potentiates
      obesity, without exacerbating metabolic complications. Only the 14-3-3zeta
      isoform is essential for adipogenesis based on isoform-specific RNAi. Mechanistic
      studies show that 14-3-3zeta depletion promotes autophagy-dependent degradation
      of C/EBP-delta, preventing induction of the master adipogenic factors, Ppargamma
      and C/EBP-alpha. Transcriptomic data indicate that 14-3-3zeta acts upstream of
      hedgehog signalling-dependent upregulation of Cdkn1b/p27(Kip1). Indeed,
      concomitant knockdown of p27(Kip1) or Gli3 rescues the early block in
      adipogenesis induced by 14-3-3zeta knockdown in vitro. Adipocyte precursors in 14
      3-3zetaKO embryos also appear to have greater Gli3 and p27(Kip1) abundance.
      Together, our in vivo and in vitro findings demonstrate that 14-3-3zeta is a
      critical upstream driver of adipogenesis. 

PMID- 26220404
TI  - SNORD116 and SNORD115 change expression of multiple genes and modify each other's
      activity.
AB  - The loss of two gene clusters encoding small nucleolar RNAs, SNORD115 and
      SNORD116 contribute to Prader-Willi syndrome (PWS), the most common syndromic
      form of obesity in humans. SNORD115 and SNORD116 are considered to be orphan C/D
      box snoRNAs (SNORDs) as they do not target rRNAs or snRNAs. SNORD115 exhibits
      sequence complementarity towards the serotonin receptor 2C, but SNORD116 shows no
      extended complementarities to known RNAs. To identify molecular targets, we
      performed genome-wide array analysis after overexpressing SNORD115 and SNORD116
      in HEK 293T cells, either alone or together. We found that SNORD116 changes the
      expression of over 200 genes. SNORD116 mainly changed mRNA expression levels.
      Surprisingly, we found that SNORD115 changes SNORD116's influence on gene
      expression. In similar experiments, we compared gene expression in post-mortem
      hypothalamus between individuals with PWS and aged-matched controls. The synopsis
      of these experiments resulted in 23 genes whose expression levels were influenced
      by SNORD116. Together our results indicate that SNORD115 and SNORD116 influence
      expression levels of multiple genes and modify each other activity. 

PMID- 26220405
TI  - Succinic semialdehyde dehydrogenase deficiency of four Chinese patients and
      prenatal diagnosis for three fetuses.
AB  - Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal
      recessive disorder that affects the degradation of gamma-aminobutyric acid
      (GABA). Only a few cases of SSADH deficiency have been documented in mainland
      China and prenatal diagnosis has not been performed. SSADH deficiency in four
      patients (three girls and one boy) from four unrelated Chinese families was
      detected by selective screening at the age of 50days to 1year. Four patients were
      admitted due to intractable seizures and psychomotor retardation. Their urine 4
      hydroxybutyric acid was significantly elevated. Seven mutations in their ALDH5A1
      gene were identified, of which the following six were novel: c.127-128insGGCCC
      (p.Q43Rfs*50), [corrected] c.615delT (p.F206Sfs*5), c.1313T>C (p.L438P),
      c.1568C>T (p.S523F), 1383-2delA and a 0.15-Mb deletion harboring ALDH5A1. Only
      one mutation, c.820C>T, had been previously reported. Three mothers of Patients 1
      3 underwent amniocentesis during their third pregnancy and the fetuses were not
      affected by SSADH deficiency. Normal development and urine organic acid levels of
      the infants confirmed the prenatal diagnosis after birth.

PMID- 26220406
TI  - Surgical reduction and ligament reconstruction for chronic dorsal dislocation of
      the lesser metatarsophalangeal joint associated with hallux valgus.
AB  - BACKGROUND: Hallux valgus (HV) is occasionally associated with chronic
      dislocation of the lesser metatarsophalangeal (MTP) joints. We have developed a
      novel surgical procedure to treat dislocation of the lesser MTP joints. This
      study aimed to describe our procedure and investigate the outcomes of surgical
      intervention in the treatment of HV with dislocation of the lesser MTP joints.
      METHODS: Twenty-three patients (27 feet, average age: 63.6 years, average follow
      up: 49.5 months; a minimum follow-up of 24 months) underwent surgical
      intervention for HV and dislocation of the lesser MTP joints. Twenty-three feet
      had dislocation (10 feet) or subluxation (13 feet) of the second MTP joint,
      whereas 4 feet had dislocation of the second and third MTP joints. The surgical
      procedure included a distal soft-tissue procedure combined with proximal
      osteotomy for correction of the HV, and reconstruction of the collateral
      ligaments (CL) following open reduction with complete release of the capsule and
      the CL at the metatarsal head for dislocation of the lesser MTP joints. Outcomes
      were assessed using the Japanese Society for Surgery of the Foot (JSSF) scale and
      radiological examinations. RESULTS: The JSSF score improved significantly from an
      average of 49.7 points preoperatively to 93.1 points postoperatively. The average
      HV angle and intermetatarsal angle decreased significantly from 44.6 degrees  and
      18.1 degrees  preoperatively to 7.9 degrees  and 6.0 degrees  postoperatively,
      respectively. The average extension and flexion of the second MTP joint was 53.1
      degrees  and 13.8 degrees  at the most recent follow-up, respectively.
      Postoperatively, no feet had dislocation of the second or third MTP joint, three
      had subluxation of the second MTP joint, and one had subluxation of the third MTP
      joint. Osteoarthritis of the lesser MTP joint had developed in two feet (7.4 %)
      at the time of the most recent follow-up. CONCLUSION: Our surgical procedure
      achieved significant correction of HV, a low rate of postoperative re-dislocation
      of the lesser MTP joints, and significant improvement of pain and function for
      symptomatic moderate-to-severe HV with dislocation of the lesser MTP joints.
      LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 26220407
TI  - Alkaline-Earth-Promoted CO Homologation and Reductive Catalysis.
AB  - Reaction between a beta-diketiminato magnesium hydride and carbon monoxide
      results in the isolation of a dimeric cis-enediolate species through the
      reductive coupling of two CO molecules. Under catalytic conditions with PhSiH3 ,
      an observable magnesium formyl species may be intercepted for the mild reductive
      cleavage of the CO triple bond. 

PMID- 26220408
TI  - Endovascular stroke therapy with the Aperio thrombectomy device.
AB  - BACKGROUND: The pharmaceutical therapy for acute ischemic stroke has shortcomings
      in reopening large vessels and dissolving long thrombi, and endovascular
      treatment has been found to provide added value. The Aperio thrombectomy device
      showed promising results in an experimental study. The purpose of this study was
      to evaluate the device clinically. METHODS: 119 patients with acute stroke were
      treated in nine centers using the Aperio thrombectomy device. Target vessel,
      diameter, thrombus length, procedure time, recanalization, number of deployments,
      additional use of anticoagulants, complications, and the use of additional
      devices were assessed. RESULTS: The median thrombus length was 15 mm (range 1.5
      20 mm) and the average time from device insertion to recanalization was 30 min
      (range 5-120 min). Blood flow restoration (Thrombolysis In Cerebral Infarction
      (TICI) 2-3) was achieved in 85%. In the majority of cases complete clot removal
      was achieved (TICI 0, 12%; TICI 1, 2%; TICI 2a, 14%; TICI 2b, 18%; TICI 3, 53%).
      The median number of deployments was 2 (range 1-6). Twelve procedural
      complications (10%) occurred. CONCLUSIONS: The Aperio thrombectomy device seems
      to be an effective and adequately safe tool for reopening occluded cerebral
      arteries in the setting of acute stroke.

PMID- 26220409
TI  - MACRA: background, opportunities and challenges for the neurointerventional
      specialist.
AB  - The legislative branch of government took many by surprise when it announced the
      Medicare Access and CHIP Reauthorization Act of 2015. Once the Act was passed,
      President Obama quickly signed this bipartisan, bicameral effort into law. A
      foundational element of this legislation was the permanent repeal of the
      sustainable growth rate formula. Physicians and their patients were appropriately
      enthusiastic about this development. The Medicare Access and CHIP Reauthorization
      Act of 2015 included additional elements of considerable interest to
      neurointerventional specialists. 

PMID- 26220411
TI  - Grading of Regional Apposition after Flow-Diverter Treatment (GRAFT): a
      comparative evaluation of VasoCT and intravascular OCT.
AB  - BACKGROUND: Poor vessel wall apposition of flow diverter (FD) stents poses risks
      for stroke-related complications when treating intracranial aneurysms,
      necessitating long-term surveillance imaging. To facilitate quantitative
      evaluation of deployed devices, a novel algorithm is presented that generates
      intuitive two-dimensional representations of wall apposition from either high
      resolution contrast-enhanced cone-beam CT (VasoCT) or intravascular optical
      coherence tomography (OCT) images. METHODS: VasoCT and OCT images were obtained
      after FD implant (n=8 aneurysms) in an experimental sidewall aneurysm model in
      canines. Surface models of the vessel wall and FD device were extracted, and the
      distance between them was presented on a two-dimensional flattened map. Maps and
      cross-sections at potential locations of malapposition detected on VasoCT-based
      maps were compared. The performance of OCT-based apposition detection was
      evaluated on manually labeled cross-sections using logistic regression against a
      thresholded (>=0.25 mm) apposition measure. RESULTS: VasoCT and OCT acquisitions
      yielded similar Grading of Regional Apposition after Flow-Diverter Treatment
      (GRAFT) apposition maps. GRAFT maps from VasoCT highlighted 16 potential
      locations of malapposition, of which two were found to represent malapposed
      device struts. Logistic regression showed that OCT could detect malapposition
      with a sensitivity of 98% and a specificity of 81%. CONCLUSIONS: GRAFT delivered
      quantitative and visually convenient representations of potential FD
      malapposition and occasional acute thrombus formation. A powerful combination for
      future neuroendovascular applications is foreseen with the superior resolution
      delivered by intravascular OCT.

PMID- 26220412
TI  - Effectiveness of interprofessional education by on-field training for medical
      students, with a pre-post design.
AB  - BACKGROUND: Interprofessional Education (IPE) implies how to achieve successful
      teamwork, and is based on collaborative practice which enhance occasions for
      relationships between two or more healthcare professions. This study evaluates
      the effectiveness of IPE in changing attitudes after a training recently
      introduced to medical education for second-year students at the University of
      Padova, Italy. METHODS: All medical students following a new program for IPE were
      enrolled in this study. The Interdisciplinary Education Perception Scale (IEPS)
      was administered before and after training, according to observation-based and
      practice-based learning. Data were analysed with Student's paired t-test and
      Wilcoxon's signed rank test. RESULTS: 277 medical students completed both
      questionnaires. Statistically significant improvements were found in students'
      overall attitudes as measured by the IEPS and four subscale scores. Gender
      stratified analyses showed that improvements were observed only in female
      students in subscale 4 ("Understanding Others' Values"). Students who had a
      physician and/or health worker in their family did not show any improvement in
      subscales 2 ("Perceived need for cooperation") or 4 ("Understanding Others'
      Values"). CONCLUSIONS: Our results indicate that IPE training has a positive
      influence on students' understanding of collaboration and better attitudes in
      interprofessional teamwork. More research is needed to explore other factors
      which may influence specific perceptions among medical students.

PMID- 26220413
TI  - The Longevity Legacy of World War II: The Intersection of GI Status and
      Mortality.
AB  - PURPOSE OF THE STUDY: We examine hypotheses involving the potential health
      advantages of selection into military service and the potential health
      disadvantages associated with the experience of military service by comparing
      later-life mortality rates for veterans and nonveterans as well as among veterans
      based on their cohort of reentry into civilian life. DESIGN AND METHODS: We use
      data on 3,453 men, including 1,496 veterans from the older men cohort of the
      National Longitudinal Surveys to estimate Cox proportional hazard mortality
      models. We distinguish between veterans and nonveterans and further classify
      veterans by age at exit while incorporating measures associated with military
      selection, health behaviors, and socioeconomic status. RESULTS: Veterans who were
      discharged from the military at older ages have a mortality advantage relative to
      veterans discharged at younger ages. For the 1914-1921 birth cohorts, the
      mortality advantage for veterans who exited around age 30 is apparent for deaths
      before age 65, but rates equalize across all groups when deaths at older ages are
      included. These findings are robust to the inclusion of background
      characteristics, education, occupation, body mass index, smoking, marital status,
      and proxies for service deferments. IMPLICATIONS: Rather than focusing on a
      general health effect of military service, per se, future research should
      distinguish among individual traits; the nature, timing, and duration of
      exposures relative to life course stage; and the sociohistorical context of
      military service to expand our understanding of the differential health
      consequences of military service.

PMID- 26220414
TI  - Combat Exposure in Early Adulthood Interacts with Recent Stressors to Predict
      PTSD in Aging Male Veterans.
AB  - PURPOSE OF THE STUDY: Combat is a risk factor for posttraumatic stress disorder
      (PTSD); however, less is known about how exposure to combat in early adulthood
      may contribute to the development of PTSD as the individual ages. Prior exposure
      to trauma may "sensitize" people to respond more intensely to subsequent
      stressors. Further, aging initiates new challenges that may undermine previous
      coping strategies. Over the life course combat veterans may be more reactive to
      new stressors and thus be more vulnerable to PTSD. DESIGN AND METHODS: This study
      draws on the two waves of the National Comorbidity Survey (NCS-1) and NCS-2 (10
      year follow-up). Participants were male (noncombat N = 620 and combat N = 107)
      and 50-65 years of age at Wave-2. At baseline, participants were assessed for
      exposure to wartime combat, number of Diagnostic and Statistical Manual of Mental
      Disorders (DSM) diagnoses in the past year, and life-time PTSD. At follow-up,
      PTSD occurring between waves was determined. A measure of recent life stressors
      was also obtained. RESULTS: Using logistic regression analyses, combat predicted
      PTSD at follow-up (controlling for baseline demographics, number of DSM diagnoses
      in the past year, life-time PTSD). Recent life stressors were also associated
      with PTSD. Importantly, the effect of combat on PTSD was significant at high
      levels, but not low levels, of recent life stress. IMPLICATIONS: Veterans who
      have experienced combat may be more reactive to new stressors, and in turn be
      more vulnerable to PTSD. Combat veterans should be regularly assessed for current
      stressors and PTSD.

PMID- 26220415
TI  - Effects of Posttraumatic Stress Disorder and Metabolic Syndrome on Cognitive
      Aging in Veterans.
AB  - PURPOSE OF THE STUDY: With the influx of veterans entering older adulthood, it is
      increasingly important to understand risk factors for cognitive decline.
      Posttraumatic stress disorder (PTSD) and the metabolic syndrome (MetS) are highly
      prevalent in older veterans. Although both increase risk for cognitive decline
      and often co-occur, it is unclear how they may interact to negatively impact
      cognition. The aim of this cross-sectional study was to investigate associations
      among PTSD, MetS, and cognitive function in older veterans. We hypothesized that
      co-occurring PTSD and MetS would be associated with worse cognitive performance
      than seen in either illness alone. DESIGN AND METHODS: Participants completed
      cognitive testing to assess processing speed, verbal memory, and executive
      function. Data from 204 male veterans aged 55-89 were analyzed with the use of
      hierarchical multiple regression models. RESULTS: Veterans with MetS demonstrated
      poorer performance on tasks of executive function (response inhibition and
      cognitive set shifting) and immediate verbal memory regardless of PTSD status.
      There was an interaction between MetS and PTSD on delayed verbal memory,
      suggesting that the negative impact of MetS on verbal memory was only significant
      for veterans not classified as having PTSD. IMPLICATIONS: This is the first study
      to examine the impact of comorbid PTSD and MetS on cognition. The results suggest
      that MetS is associated with poorer verbal learning and executive functioning
      independent of PTSD. We discuss the necessity of monitoring cerebrovascular risk
      factors and providing early behavioral and/or pharmaceutical interventions to
      lessen the risk of cognitive decline in older age.

PMID- 26220416
TI  - How Does Survey Context Impact Self-reported Fraud Victimization?
AB  - Purpose of the Study: This study examines the effect of survey context on self
      reported rates of personal fraud victimization, and explores if the effect is
      influenced by age and gender. Design and Methods: Participants (3,000U.S. adults)
      were randomly assigned to 1 of the 3 versions of a fraud victimization
      questionnaire: questions about fraud were identical across conditions, however,
      the context varies. One questionnaire asked about crime, one about consumer
      buying experiences, and a third focused only on fraud. Results: Participants who
      were asked about fraud victimization in the context of crime reported
      significantly less victimization (p < .05) than those in the fraud-alone
      condition, yet the number of reports from those asked within the context of a
      consumer survey did not differ from the fraud-alone condition. The effect of the
      crime context interacted with age (p < .05), such that there was no effect of
      survey context for the middle age group (35-64), and a strong effect for younger
      (25-34) and older (65 plus) adults. The combined effect of being female and older
      was associated with the greatest effect of crime context on self-reported fraud
      victimization. Implications: These findings inform the production of new surveys
      and guide the development of effective social and health policies.

PMID- 26220417
TI  - Stereotypes Associated With Age-related Conditions and Assistive Device Use in
      Canadian Media.
AB  - PURPOSE OF THE STUDY: Newspapers are an important source of information. The
      discourses within the media can influence public attitudes and support or
      discourage stereotypical portrayals of older individuals. This study critically
      examined discourses within a Canadian newspaper in terms of stereotypical
      depictions of age-related health conditions and assistive technology devices
      (ATDs). DESIGN AND METHODS: Four years (2009-2013) of Globe and Mail articles
      were searched for terms relevant to the research question. A total of 65 articles
      were retained, and a critical discourse analysis (CDA) of the texts was
      conducted. The articles were coded for stereotypes associated with age-related
      health conditions and ATDs, consequences of the stereotyping, and context
      (overall setting or background) of the discourse. RESULTS: The primary code list
      included 4 contexts, 13 stereotypes, and 9 consequences of stereotyping. CDA
      revealed discourses relating to (a) maintaining autonomy in a stereotypical
      world, (b) ATDs as obstacles in employment, (c) barriers to help seeking for age
      related conditions, and (d) people in power setting the stage for discrimination.
      IMPLICATIONS: Our findings indicate that discourses in the Canadian media include
      stereotypes associated with age-related health conditions. Further, depictions of
      health conditions and ATDs may exacerbate existing stereotypes about older
      individuals, limit the options available to them, lead to a reduction in help
      seeking, and lower ATD use. Education about the realities of age-related health
      changes and ATDs is needed in order to diminish stereotypes and encourage ATD
      uptake and use.

PMID- 26220418
TI  - Vasomotor Symptoms and Quality of Life Among Veteran and Non-Veteran
      Postmenopausal Women.
AB  - INTRODUCTION: Vasomotor symptoms (VMS), including hot flashes and night sweats,
      are common among postmenopausal women and are associated with reduced health
      related quality of life (HRQOL). PURPOSE OF THE STUDY: To determine whether
      Veterans are more likely to report VMS than non-Veterans, and whether the
      association of VMS with HRQOL varies by Veteran status. DESIGN AND METHODS: We
      used data from the Women's Health Initiative Observational Study, including self
      reported baseline VMS presence and severity, and HRQOL at follow-up Year 3 (RAND
      Short Form 36-Item Health Survey). Employing generalized linear models we
      estimated whether Veteran status was associated with any VMS. We estimated the
      association between any VMS and HRQOL using linear regression, stratified by
      Veteran status. Interaction terms were added separately to determine whether the
      association varied by baseline depression, obesity, or smoking status. RESULTS:
      The final analyses included 77,153 postmenopausal women (2,004 Veterans). After
      adjustment, Veterans were no more likely than non-Veterans to report any VMS at
      baseline (relative risk [RR] 0.97, 95% confidence interval [CI] 0.90-1.04) or
      moderate to severe VMS (RR 1.03, 95% CI 0.89-1.18). Any VMS was associated with
      decreased HRQOL at Year 3, particularly among Veterans (mean difference range:
      Veterans -2.7 to -4.6, p-values < .001; non-Veterans -2.2 to -2.6, 95% CI -0.13
      to -0.09, p values < .001). Baseline depression and obesity, but not smoking,
      amplified the negative association between VMS and HRQOL. IMPLICATIONS:
      Multicondition care models for postmenopausal Veteran and non-Veteran women are
      needed that incorporate management strategies for VMS, weight, and depression.

PMID- 26220419
TI  - Older People's Discourses About Euthanasia and Assisted Suicide: A Foucauldian
      Exploration.
AB  - PURPOSE OF THE STUDY: This study aims to contribute an alternative understanding
      of the position of older people in the euthanasia and assisted suicide (EU/AS)
      debate. DESIGN AND METHODS: Seven interviews were analyzed using Foucauldian
      discourse analysis, to explore concepts like knowledge, power, subjectification
      and surveillance. RESULTS: The participants presented a "confused and conflicted"
      discourse, expressing the view that EU/AS is a family affair, whilst also
      articulating a strong sense of self-determination. Although a discourse of the
      medicalization of dying through medical control and surveillance was endorsed, an
      alternative discourse of "dying outside the medical gaze" emerged. Participants,
      who were in favor of EU/AS, felt "voiceless," as apparent double standards were
      applied in the debate, and powerful others, for example, physicians and
      politicians, seemed reluctant to engage. Within an "aged death" discourse, the
      anticipated dependency on poor care from (professional) others, made participants
      consider EU/AS as ways of avoiding this stage of life and the associated loss of
      dignity. IMPLICATIONS: By using Foucauldian discourse analysis, alternative power
      relationships were revealed which might give a different interpretation to the
      concept of the "slippery slope." Societal discourses and related behaviors, which
      devalue the dependent and old, might become internalized by older people, leading
      them to consider EU/AS as preferable end-of-life options.

PMID- 26220420
TI  - Factors associated with unreported tuberculosis cases in Spanish hospitals.
AB  - BACKGROUND: Under-reporting of tuberculosis (TB) cases complicates disease
      control, hinders contact tracing and alters the accuracy of epidemiological data,
      including disease burden. The objective of the present study is to evaluate the
      proportion of unreported TB cases in Spanish healthcare facilities and to
      identify the associated factors. METHODS: A multi-center retrospective study
      design was employed. The study included TB cases diagnosed in 16 facilities
      during 2011-2012. These cases were compared to those reported to the
      corresponding public health departments. Demographic, microbiological and
      clinical data were analyzed to determine the factors associated with unreported
      cases. Associated factors were analyzed on a bivariate level using the x(2) test
      and on a multivariate level using a logistic regression. Odds ratios (OR) and 95
      % confidence intervals (CI) were calculated. RESULTS: Of the 592 TB cases
      included in the study, 85 (14.4 %) were not reported. The percentage of
      unreported cases per healthcare center ranged from 0-45.2 %. The following
      variables were associated to under-reporting at a multivariate level: smear
      negative TB (OR = 1.87; CI:1.07-3.28), extrapulmonary disease (OR = 2.07; CI:1.05
      4.09) and retired patients (OR = 3.04; CI:1.29-7.18). A nurse case manager was
      present in all of the centers with 100 % reporting. The percentage of reported
      cases among the smear-positive cases was 9.4 % and 19.4 % (p = 0.001) among the
      rest of the study population. Smear-positive TB was no associated to under
      reporting. CONCLUSIONS: It is important that TB Control Programs encourage
      thorough case reporting to improve disease control, contact tracing and accuracy
      of epidemiological data. The help from a TB nurse case manager could improve the
      rate of under-reporting.

PMID- 26220422
TI  - Corrigenda.

PMID- 26220421
TI  - Vascular permeability--the essentials.
AB  - The vasculature, composed of vessels of different morphology and function,
      distributes blood to all tissues and maintains physiological tissue homeostasis.
      In pathologies, the vasculature is often affected by, and engaged in, the disease
      process. This may result in excessive formation of new, unstable, and
      hyperpermeable vessels with poor blood flow, which further promotes hypoxia and
      disease propagation. Chronic vessel permeability may also facilitate metastatic
      spread of cancer. Thus, there is a strong incentive to learn more about an
      important aspect of vessel biology in health and disease: the regulation of
      vessel permeability. The current review aims to summarize current insights into
      different mechanisms of vascular permeability, its regulatory factors, and the
      consequences for disease. 

PMID- 26220424
TI  - Characterization and Validation of a Canine Pruritic Model.
AB  - Preclinical Research The mechanisms mediating canine pruritus are poorly
      understood with few models due to limited methods for inducing pruritus in dogs.
      Chloroquine (CQ) is a widely used antimalarial drug that causes pruritus in
      humans and mice. We have developed a canine model of pruritus where CQ reliably
      induced pruritus in all dogs tested following intravenous administration. This
      model is presently being used to test antipruritic activity of drug candidate
      molecules. This publication has been validated in a blinded cross-over study in
      eight beagle dogs using the reference standards, oclacitinib and prednisolone,
      and has been used to test a new compound, norketotifen. All compounds reduced CQ
      induced pruritus in the dog. The sensitivity of the model was demonstrated using
      norketotifen, which at three dose levels, dose-dependently, inhibited scratching
      events compared with placebo.

PMID- 26220423
TI  - Detection of KRAS, NRAS and BRAF by mass spectrometry - a sensitive, reliable,
      fast and cost-effective technique.
AB  - BACKGROUND: According to current clinical guidelines mutational analysis for KRAS
      and NRAS is recommended prior to EGFR-directed therapy of colorectal cancer (CRC)
      in the metastatic setting. Therefore, reliable, fast, sensitive and cost
      effective methods for routine tissue based molecular diagnostics are required
      that allow the assessment of the CRC mutational status in a high throughput
      fashion. METHODS: We have developed a custom designed assay for routine mass
      spectrometric (MS) (MassARRAY, Agena Bioscience) analysis to test the
      presence/absence of 18 KRAS, 14 NRAS and 4 BRAF mutations. We have applied this
      assay to 93 samples from patients with CRC and have compared the results with
      Sanger sequencing and a chip hybridization assay (KRAS LCD-array Kit, Chipron).
      In cases with discordant results, next-generation sequencing (NGS) was performed.
      RESULTS: MS detected a KRAS mutation in 46/93 (49%), a NRAS mutation in 2/93 (2%)
      and a BRAF mutation in 1/93 (1%) of the cases. MS results were in agreement with
      results obtained by combination of the two other methods in 92 (99%) of 93 cases.
      In 1/93 (1%) of the cases a G12V mutation has been detected by Sanger sequencing
      and MS, but not by the chip assay. In this case, NGS has confirmed the G12V
      mutation in KRAS. CONCLUSIONS: Mutational analysis by MS is a reliable method for
      routine diagnostic use, which can be easily extended for testing of additional
      mutations.

PMID- 26220425
TI  - Charging Fuss.

PMID- 26220426
TI  - Upper Extremity Sarcoma Reconstruction with a Pedicle Thoracodorsal Artery
      Perforator Flap.

PMID- 26220427
TI  - Supraorbital Neuroma: A Rare and Unreported Complication Following
      Blepharoplasty.

PMID- 26220428
TI  - Selecting a Test for Leprous Neuropathy Screening.
AB  - BACKGROUND: Worldwide, leprosy represents a significant cause of disability due
      to progressive neurological impairment. Screening for leprous neuropathy is
      performed with Semmes-Weinstein monofilament (SWM) or ballpoint pen testing
      (BPT), which results in underreporting of its prevalence. The Pressure-specified
      sensory device (PSSD; Sensory Management Services, LLC, Baltimore, MD) is a
      sensitive, noninvasive, portable, neurosensory instrument, which has not been
      field-tested for leprosy screening. Early identification of leprous neuropathy
      would permit early antibiotic treatment to prevent contagion and early
      microsurgical neurolysis. METHODS: A prospective, clinical diagnostic, cross
      sectional study screened a consecutive sample of patients for leprous neuropathy
      in the leprosy-endemic province of Los Rios, Ecuador. Patients meeting the World
      Health Organization criteria for leprosy and complaining of neuropathy symptoms
      were classified as leprous neuropathy patients. Patients without any signs of
      leprosy were used as normal controls. Bilateral ulnar nerve screening with the
      PSSD, SWM (0.07, 0.4, 2, 4, 10, and 300 g), and BPT was performed in all
      patients. Sensitivity and specificity were calculated and compared across tests.
      A total of 71 patients (142 nerves) were evaluated. RESULTS: Compared with the 10
      g SWM and the BPT, the PSSD was found to have significantly higher sensitivity
      (78.3 vs. 0% with p < 0.001, for both) with comparable specificity (97.8 vs. 100%
      with p > 0.999, for both). Compared with the 0.07 g SWM (lightest filament in our
      series), the PSSD showed better sensitivity (78.3 vs. 65.2%, p = 0.514) and
      significantly higher specificity (97.8 vs. 51.1%, p < 0.001). CONCLUSIONS: The
      PSSD provides superior diagnostic accuracy for detecting leprous neuropathy as
      compared with SWM and BPT.

PMID- 26220429
TI  - Improving Fellowship Training in Microsurgery: A Threshold Concepts Perspective
      on the Curricula of Fellowship Programs.
AB  - BACKGROUND: The theory of "threshold concepts" argues that within every
      discipline there is knowledge that transforms understanding and leads to a
      previously inaccessible way of thinking, without which the learner cannot
      progress. This study investigates the factors influencing the development of the
      characteristic ways of thinking and practicing as a microsurgeon during a
      microsurgical fellowship. We analyze the challenges in the development of these
      characteristics during focused fellowship training in microsurgery, of which some
      could potentially represent "threshold concepts." METHODS: A qualitative research
      methodology was followed. Semistructured interviews with trainers and trainees
      from microsurgical units in the United Kingdom (UK) and the United States (US)
      were conducted. Data were analyzed using the Dedoose (Manhattan Beach, CA)
      qualitative data analysis software and interpreted using the theory of "threshold
      concepts." RESULTS: Five trainees and four trainers from the UK and the US
      participated in this research project. Although initially some trainees had
      particular difficulty in developing their practical microsurgical skills, this
      improved rapidly with adequate practice. Cognitive skills and especially the
      ability to expect the unexpected and the ability recognize complications
      presented as a significant challenge for trainees and transformed their
      understandings regarding the qualities of a microsurgeon. CONCLUSIONS:
      Microsurgical fellowship curricula can be redesigned using the theory of
      threshold concepts, creating a dynamic framework that addresses individual
      trainee needs to develop the practical and cognitive skills necessary for
      independent practice of microsurgery.

PMID- 26220431
TI  - Reconstruction of Moderate-Sized Distal Limb Defects using a Superthin
      Superficial Circumflex Iliac Artery Perforator Flap.
AB  - BACKGROUND: When using groin flaps the scars can be easily covered. However,
      disadvantages including short pedicle lengths, anatomical variations in the
      vessels, and flap bulkiness, have prevented their widespread use. We examined the
      use of superficial circumflex iliac artery perforator (SCIP) free flaps to
      moderate-sized defects in the distal extremities. METHODS: From July 2011 to
      August 2014, 52 patients underwent reconstructions using SCIP free flaps for
      moderate-sized defects in the distal upper and lower extremities. We measured the
      flap sizes and the thicknesses and pedicle lengths. RESULTS: The mean flap size
      was 75 cm(2). The flaps were up to 7 cm wide as all donor sites underwent primary
      closure. The mean flap thickness was 5 mm, and mean pedicle length was 4.5 cm.
      Two cases showed total necrosis, and two cases showed partial losses in the flap
      margins. Among the two cases with partial necrosis, one case was managed using
      conservative treatment without surgery, whereas the other case underwent
      secondary skin-graft surgery. CONCLUSION: We reconstructed moderate-sized defects
      in the distal upper and lower extremities using SCIP flaps, and observed that
      SCIP flaps have several advantages. After applying thin flaps to the defects, the
      contour of the flap site appeared symmetrical and natural when compared with the
      uninjured contralateral side of the distal limb, and no debulking surgery was
      required. No complications were observed at donor sites, and the surgical scars
      were well concealed by underwear.

PMID- 26220430
TI  - Early Postoperative Complications following Gracilis Free Muscle Transfer for
      Facial Reanimation: A Systematic Review and Pooled Data Analysis.
AB  - BACKGROUND: Multiple studies have detailed promising smile restoration following
      gracilis free muscle transfer for facial reanimation but information detailing
      the potential complications is lacking. The aim of this study is to
      systematically review the literature to evaluate the reported complication rate
      associated with this procedure. We also aim to determine the most common
      occurring complications. METHODS: The PubMed, Embase, and Web of Science
      databases were queried with multiple search strategies for published articles
      between January 1950 and February 2013 that detailed gracilis free muscle
      transfer for facial reanimation. Title, abstract, and full text review was
      performed. Complications were defined as any reported, identifiable adverse
      outcome that required an alteration in treatment for correction. RESULTS: The
      literature search yielded 62 studies of gracilis free muscle transfer for facial
      reanimation. Overall, 36 articles (58%) reported whether or not a complication
      had occurred. The overall complication rate based on pooled proportions was 9.6%
      and the most commonly occurring complications were postoperative hematoma (3.6%)
      and infection (3.5%). CONCLUSIONS: Our data suggests that complications after
      gracilis free muscle transfer for facial reanimation may be underreported and
      this complex procedure may in fact be associated with significant adverse
      outcomes as high as 9.6%.

PMID- 26220432
TI  - Basic Science of Muscle Neurotization: A Review.
AB  - Traumatic nerve injuries continue to be considered a challenge in the field of
      nerve microsurgical reconstruction. Despite the advances in microsurgical repair
      techniques, motor function recovery is not adequate in severe nerve injuries,
      especially when there is separation of the motor nerve from the muscle tissue.
      The technique of reinnervating skeletal muscles by insertion within it of a donor
      nerve was developed at the beginning of the 20th century during World War I, when
      injuries and poliomyelitis produced paralytics for whom no therapy was available.
      Only a few reports of clinically successful reinnervation exist, and clinical
      application of the method during the following decades has been limited. However,
      the functional value of this procedure remains a matter of controversy. The
      purpose of this review is to present what is known in basic science about direct
      neurotization of muscle along with a brief historical review. 

PMID- 26220433
TI  - Use of Flow-Through Anterolateral Thigh Perforator Flaps in Reconstruction of
      Complex Extremity Defects.
AB  - BACKGROUND: The flow-through flap has been widely utilized for reconstruction of
      complex defects of the extremities as it can be used for arterial reconstruction
      and soft-tissue coverage simultaneously. This study describes our clinical
      experience with the application of the flow-through anterolateral thigh
      perforator (ALTP) flap for reconstruction of complex defects of the extremities.
      METHODS: From January 2008 to June 2011, we retrospectively analyzed 16 patients
      with complex defects in the limbs. In two patients the defects occurred after
      undergoing wide excision of chronic ulcer, while 14 defects were due to trauma.
      All patients in this series underwent reconstruction with the flow-through ALTP
      flap. Applications of flow-through performed include preserving the recipient
      artery flow, rebuilding the major artery gap, bridging the artery and concomitant
      vein simultaneously, and combining the ALTP with another free flap. RESULTS: Flow
      through ALTP flaps were used to preserve recipient flow (n = 5), rebuild the
      vessel gap (n = 2), bridge the artery and concomitant vein simultaneously (n =
      2), and in combination with another free flap (n = 7). Follow-up ranged from 3 to
      36 months (mean, 12 months). All flaps were successful; only two combination
      flaps required reexploration because of vessel crisis, and two patients suffered
      minor degrees of wound-edge necrosis. The donor sites healed well in all cases,
      without any complications. CONCLUSION: Our experience showed that the flow
      through ALTP flap is reliable and suitable for reconstruction of complex defects
      of the extremities, as well as for various other clinical purposes.

PMID- 26220434
TI  - Free Jejunal Flap for Pharyngoesophageal Reconstruction in Head and Neck Cancer
      Patients: An Evaluation of Donor-Site Complications.
AB  - BACKGROUND: Free jejunal transfer for pharyngoesophageal reconstruction has often
      been criticized for its associated donor-site morbidity. Conversely, the same
      argument has been invoked to support use of fasciocutaneous flaps, given their
      low incidence of donor-site complications. The purpose of the current study was
      to document donor-site complication rate with free jejunal flaps for
      pharyngoesophageal reconstruction, in the hands of an experienced surgeon.
      METHODS: A retrospective chart review was performed for consecutive patients who
      underwent free jejunal transfer between 1992 and 2012 by the senior author
      (P.G.C.). Demographic data, abdominal complications, surgical characteristics of
      small bowel anastomoses, and postoperative bowel function were specifically
      noted. RESULTS: Overall, 92 jejunal flap reconstructions were performed in 90
      patients. The mean follow-up time was 29 months. Twelve (13%) patients had prior
      abdominal surgery. Donor-site complications included ileus (n = 2), wound
      cellulitis (n = 1), wound dehiscence (n = 1), and small bowel obstruction (n =
      1). Mean time to initiation of tube feeds after reconstruction was 5 days. A
      total of 77 (86.5%) patients were discharged on an oral diet. The perioperative
      mortality rate of 2% was not associated with any donor-site complication.
      CONCLUSION: Free jejunal transfer is associated with minimal and acceptable donor
      site complication rates. The choice of flap for pharyngoesophageal reconstruction
      should be determined by the type of defect, potential recipient site
      complications, and the surgeon's familiarity with the flap. Potential donor-site
      complications should not be a deterrent for free jejunal flaps given the low rate
      described in this study.

PMID- 26220435
TI  - Extended Scope of the Use of the Peroneal Perforator Flap in Lower Limb
      Reconstruction.
AB  - BACKGROUND: The advantages of the peroneal perforator flap include a short
      harvesting time, thinness, and pliability. Due to the presence of a short pedicle
      and small vessel diameter, without peroneal vessel sacrifice, this flap is
      commonly used for distal limb reconstruction, but is rarely used for knee and
      proximal and middle lower leg reconstruction. We describe our experience with the
      application of a versatile peroneal perforator free flap for knee and proximal
      and middle lower leg reconstruction through supermicrosurgery. METHODS: Between
      October 2010 and August 2014, 22 patients with small-to-medium-sized defects on
      their knee and proximal and middle lower leg underwent reconstruction surgery
      using a peroneal perforator free flap. End-to-end anastomosis using a
      supermicrosurgery technique is often necessary, given the extremely small
      perforator vessel caliber (often less than 1.0 mm). RESULTS: The flap sizes
      ranged from 5 * 3 to 14 * 5.5 cm. The mean duration required for recipient
      perforator dissection was 30 minute, mean pedicle length was 4.5 cm, and mean
      duration required for flap harvesting was 31 minutes. Overall, 20 patients showed
      no complications; 1 case each showed total and partial necrosis. CONCLUSION: The
      use of a peroneal perforator free flap for knee and proximal and middle lower leg
      reconstruction, via supermicrosurgery, for small- and medium-sized defects had
      several advantages, including the short duration required for flap harvesting and
      securing the recipient vessel, and the avoidance of damage to a main artery.
      Moreover, the thinness and pliability of the flap ensured the absence of contour
      deformity and tissue defect mismatches.

PMID- 26220436
TI  - Surgical Treatment for Lymphedema: State of the Art.

PMID- 26220437
TI  - Synergistically enhanced photocatalytic and chemotherapeutic effects of aptamer
      functionalized ZnO nanoparticles towards cancer cells.
AB  - Today cancer is one of the most life-threatening diseases in the world. The
      conventional cancer therapies, including surgery, chemo- and radiation therapies,
      have some disadvantages, such as limited efficiency and significant side effects.
      It is necessary to develop new therapeutic treatments. Herein, we integrated the
      targeted photocatalytic and chemotherapy in a multifunctional drug-delivery
      platform. The aptamer-functionalized ZnO nanoparticles (NPs) were successfully
      synthesized. The anti-cancer drug was loaded in the aptamer-ZnO NP system. In
      vitro cell cytotoxicity experiments showed that combined therapy had a higher
      rate of death of cancer cells compared to that of single photocatalytic or
      chemotherapy. Furthermore, aptamer-functionalization could greatly increase the
      accumulation of nanoparticles within cancer cells and lead to better therapeutic
      effects. The results suggest that aptamer-functionalized semiconductor
      nanoparticles may have potential in the development of targeted photocatalytic
      and chemotherapy against cancer. 

PMID- 26220438
TI  - Two suspected MERS cases in Manchester prove negative.

PMID- 26220439
TI  - The effectiveness and safety of plum-blossom needle therapy for Tourette
      syndrome: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Previous studies have indicated that acupuncture can alleviate the
      symptoms of Tourette syndrome (TS), but the evidence is insufficient. So far,
      there have been no reports on plum-blossom needle therapy for TS. Here we present
      a protocol for a randomized controlled trial using plum-blossom needle therapy to
      treat TS. METHODS/DESIGN: Sixty patients will be randomly allocated into either
      the plum-blossom needle therapy group or the habit reversal training (HRT) group.
      All patients in each group will be given 12 weeks of treatment, with follow-up at
      the 24th week. The primary outcome measure will be the mean change from baseline
      in the total tic score on the Yale Global Tic Severity Scale (YGTSS) at the 12th
      week. Secondary outcome measures will include the scores on the TS Clinical
      Global Impression Scale (CGI) and the mean changes from baseline in the YGTSS
      score and the Children and Adolescents' Quality of Life Scale (CAQOL) at other
      time points. Safety will also be evaluated. DISCUSSION: This trial will evaluate
      the effectiveness and safety of plum-blossom needle therapy for TS compared with
      HRT. A limitation of this trial is that patients and acupuncturists cannot be
      blinded. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02403258 (Date of
      registration: March 31, 2015).

PMID- 26220440
TI  - Beneficial effects of creatine phosphate sodium for the treatment of Henoch
      Schonlein purpura in patients with early renal damage detected using urinary
      kidney injury molecule-1 levels.
AB  - Henoch-Schonlein purpura (HSP) is a small-vessel disease in children that is
      often accompanied by kidney damage. Despite many efforts to improve the early
      assessment of renal injury in HSP patients, effective markers are still lacking.
      In recent years, the relationship between kidney injury molecule-1 (KIM-1) and
      tubulointerstitial injury has drawn much attention, especially regarding the
      diagnostic potential of serum and urinary KIM-1 levels. However, the diagnostic
      value of KIM-1 for detecting urinary kidney injury in HSP patients is still
      elusive. Furthermore, the treatment of Henoch-Schonlein purpura nephritis (HSPN)
      relies on the clinician's experience without performing renal biopsy, so it is
      important to find an effective biomarker and therapy. In the present study, we
      investigated the diagnostic value of urinary KIM-1 for early renal injury in HSP
      patients enrolled in a prospective, single-center study. Urinary KIM-1 levels
      were measured in 27 patients with HSP, 32 patients with HSPN (21 HSPN patients
      had undergone renal biopsy), and 16 healthy donors, as normal controls. The HSPN
      patients were randomly divided to receive either routine therapy (n = 13) or
      routine treatment combined with creatine phosphate sodium (CP) (n = 19). Urinary
      KIM-1 levels were significantly greater in the HSP and HSPN groups than those in
      the healthy control group (P < 0.01), and were significantly greater in the HSPN
      group than in the HSP group (P < 0.01). The urinary KIM-1 levels decreased
      significantly after 10-14 days of treatment with CP compared with conventional
      therapy (P < 0.05). CONCLUSION: Our results demonstrate the diagnostic value of
      KIM-1 and the therapeutic potential of CP for early renal damage in HSP patients.
      WHAT IS KNOWN: Urine kidney injury molecule-1 (KIM-1) is a sensitive biomarker
      for tubulointerstitial injury. Henoch-Schonlein purpura (HSP) usually presents
      with renal damage. WHAT IS NEW: Our results suggest that the urinary KIM-1 level
      is a sensitive and specific biomarker for the detection of early renal damage in
      HSP and may predict the severity of HSP and HSPN. The administration of creatine
      phosphate sodium (CP) may reduce urinary KIM-1 levels and thus correct the
      hypoxic condition of the kidney. Preconditioning with CP may also be a useful
      adjunct for preventing early renal damage in HSPN patients.

PMID- 26220441
TI  - Aza-Quaternary Scaffolds from Selective Bond Cleavage of Bridgehead-Substituted 7
      Azabicyclo[2.2.1]heptane: Total Synthesis of (+)-Cylindricines C-E and (-)
      Lepadiformine A.
AB  - A novel bridgehead-substituted aza-bicyclic framework has been designed and
      developed in both enantiomeric forms through an asymmetric desymmetrization
      reaction. Strategic exploitation of the ring strain in the aza-bicyclic framework
      has been utilized for the construction of the chiral aza-quaterenary scaffolds by
      selective bond fragmentation processes. Furthermore, a strategically designed
      precursor is employed for selective bond cleavage to initiate a cascade
      rearrangement for the total synthesis of the 1-azaspirotricyclic marine alkaloids
      (+)-cylindricines C, D, and E, as well as (-)-lepadiformine A. An oxidation/retro
      aldol/aza-Michael sequence generated three new chiral centers with the required
      configuration in one pot. 

PMID- 26220442
TI  - Effectiveness of Organ Donation Information Campaigns in Germany: A Facebook
      Based Online Survey.
AB  - BACKGROUND: The German transplantation system is in a crisis due to a lack of
      donor organs. Information campaigns are one of the main approaches to increase
      organ donation rates. Since 2012, German health insurance funds are obliged by
      law to inform their members about organ donation. We raised the hypothesis: The
      willingness to sign a donor card rises due to the subsequent increase of specific
      knowledge by receiving the information material of the health insurance funds.
      OBJECTIVE: The objective of the study was to assess the influence of information
      campaigns on the specific knowledge and the willingness to donate organs.
      METHODS: We conducted an online survey based on recruitment via Facebook groups,
      advertisements using the snowball effect, and on mailing lists of medical
      faculties in Germany. Besides the demographic data, the willingness to hold an
      organ donor card was investigated. Specific knowledge regarding transplantation
      was explored using five factual questions resulting in a specific knowledge
      score. RESULTS: We recruited a total of 2484 participants, of which 32.7%
      (300/917) had received information material. Mean age was 29.9 (SD 11.0, median
      26.0). There were 65.81% (1594/2422) of the participants that were female. The
      mean knowledge score was 3.28 of a possible 5.00 (SD 1.1, median 3.0). Holding a
      donor card was associated with specific knowledge (P<.001), but not with the
      general education level (P=.155). Receiving information material was related to
      holding a donor card (P<.001), but not to a relevant increase in specific
      knowledge (difference in mean knowledge score 3.20 to 3.48, P=.006). The specific
      knowledge score and the percentage of organ donor card holders showed a linear
      association (P<.001). CONCLUSIONS: The information campaign was not associated
      with a relevant increase in specific knowledge, but with an increased rate in
      organ donor card holders. This effect is most likely related to the feeling of
      being informed, together with an easy access to the organ donor card.

PMID- 26220443
TI  - Ursidibacter maritimus gen. nov., sp. nov. and Ursidibacter arcticus sp. nov.,
      two new members of the family Pasteurellaceae isolated from the oral cavity of
      bears.
AB  - Thirty-three suspected strains of the family Pasteurellaceae isolated from the
      oral cavity of polar and brown bears were characterized by genotypic and
      phenotypic tests. Phylogenetic analysis of partial 16S rRNA gene and rpoB
      sequences showed that the investigated isolates formed two closely related
      monophyletic groups, representing two novel species of a new genus. Based on 16S
      rRNA gene sequence comparison Bibersteinia trehalosi was the closest related
      species with a validly published name, with 95.4 % similarity to the polar bear
      group and 94.4 % similarity to the brown bear group. Otariodibacter oris was the
      closest related species based on rpoB sequence comparison with a similarity of
      89.8 % with the polar bear group and 90 % with the brown bear group. The new
      genus could be separated from existing genera of the family Pasteurellaceae by
      three to ten phenotypic characters, and the two novel species could be separated
      from each other by two phenotypic characters. It is proposed that the strains
      should be classified as representatives of a new genus, Ursidibacter gen. nov.,
      with two novel species: the type species Ursidibacter maritimus sp. nov.,
      isolated from polar bears (type strain Pb43106T = CCUG 65144T = DSM 28137T, DNA
      G+C content 39.3 mol%), and Ursidibacter arcticus sp. nov., isolated from brown
      bears (type strain Bamse61T = CCUG 65145T = DSM 28138T). 

PMID- 26220444
TI  - Application of MS Transport Assays to the Four Human gamma-Aminobutyric Acid
      Transporters.
AB  - gamma-Aminobutyric acid (GABA) transporters (GATs) are promising drug targets for
      various diseases associated with imbalances in GABAergic neurotransmission. For
      the development of new drugs or pharmacological tools addressing GATs, screening
      techniques to identify new inhibitors and to characterize their potency at each
      GAT subtype are indispensable. By now, the technique by far dominating is based
      on radiolabeled GABA. We recently described "MS Transport Assays" for hGAT-1 by
      employing ((2) H6 )GABA as the substrate. In the present study, we applied this
      approach to all four human GAT subtypes and determined the KM values for GAT
      mediated transport of ((2) H6 )GABA at each subtype. Furthermore, a comprehensive
      set of GAT inhibitors reflecting the whole range of potency and subtype
      selectivity known so far was evaluated for their potency. The comparison of pIC50
      values obtained in conventional [(3) H]GABA uptake assays with those obtained in
      MS Transport Assays indicated the reliability of the latter. The MS Transport
      Assays enable a throughput similar to that of conventional radiometric transport
      assays performed in a 96-well format but avoid the use of radiolabeled
      substrates. 

PMID- 26220445
TI  - Quantitative proteomic analysis of formalin-fixed, paraffin-embedded clear cell
      renal cell carcinoma tissue using stable isotopic dimethylation of primary
      amines.
AB  - BACKGROUND: Formalin-fixed, paraffin-embedded (FFPE) tissues represent the most
      abundant resource of archived human specimens in pathology. Such tissue specimens
      are emerging as a highly valuable resource for translational proteomic studies.
      In quantitative proteomic analysis, reductive di-methylation of primary amines
      using stable isotopic formaldehyde variants is increasingly used due to its
      robustness and cost-effectiveness. RESULTS: In the present study we show for the
      first time that isotopic amine dimethylation can be used in a straightforward
      manner for the quantitative proteomic analysis of FFPE specimens without
      interference from formalin employed in the FFPE process. Isotopic amine
      dimethylation of FFPE specimens showed equal labeling efficiency as for
      cryopreserved specimens. For both FFPE and cryopreserved specimens, differential
      labeling of identical samples yielded highly similar ratio distributions within
      the expected range for dimethyl labeling. In an initial application, we profiled
      proteome changes in clear cell renal cell carcinoma (ccRCC) FFPE tissue specimens
      compared to adjacent non-malignant renal tissue. Our findings highlight increased
      levels of glyocolytic enzymes, annexins as well as ribosomal and proteasomal
      proteins. CONCLUSION: Our study establishes isotopic amine dimethylation as a
      versatile tool for quantitative proteomic analysis of FFPE specimens and
      underlines proteome alterations in ccRCC.

PMID- 26220446
TI  - Comprehensive biometric, biochemical and histopathological assessment of nutrient
      deficiencies in gilthead sea bream fed semi-purified diets.
AB  - Seven isoproteic and isolipidic semi-purified diets were formulated to assess
      specific nutrient deficiencies in sulphur amino acids (SAA), n-3 long-chain PUFA
      (n-3 LC-PUFA), phospholipids (PL), P, minerals (Min) and vitamins (Vit). The
      control diet (CTRL) contained these essential nutrients in adequate amounts. Each
      diet was allocated to triplicate groups of juvenile gilthead sea bream fed to
      satiety over an 11-week feeding trial period. Weight gain of n-3 LC-PUFA, P-Vit
      and PL-Min-SAA groups was 50, 60-75 and 80-85 % of the CTRL group, respectively.
      Fat retention was decreased by all nutrient deficiencies except by the Min diet.
      Strong effects on N retention were found in n-3 LC-PUFA and P fish. Combined
      anaemia and increased blood respiratory burst were observed in n-3 LC-PUFA fish.
      Hypoproteinaemia was found in SAA, n-3 LC-PUFA, PL and Vit fish. Derangements of
      lipid metabolism were also a common disorder, but the lipodystrophic phenotype of
      P fish was different from that of other groups. Changes in plasma levels of
      electrolytes (Ca, phosphate), metabolites (creatinine, choline) and enzyme
      activities (alkaline phosphatase) were related to specific nutrient deficiencies
      in PL, P, Min or Vit fish, whereas changes in circulating levels of growth
      hormone and insulin-like growth factor I primarily reflected the intensity of the
      nutritional stressor. Histopathological scoring of the liver and intestine
      segments showed specific nutrient-mediated changes in lipid cell vacuolisation,
      inflammation of intestinal submucosa, as well as the distribution and number of
      intestinal goblet and rodlet cells. These results contribute to define the normal
      range of variation for selected biometric, biochemical, haematological and
      histochemical markers. 

PMID- 26220447
TI  - Aripiprazole for the treatment of tic disorders in children: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Tic disorders (TDs) are common neuropsychiatric disorders in
      children. Typical antipsychotics, such as haloperidol and pimozide have been
      prescribed to control tic symptoms as first-line agents. However, adverse effects
      have led to the use of newer atypical antipsychotics. Aripiprazole is one of
      alternatives. The aim of this study was to evaluate the efficacy and safety of
      aripiprazole for children with TDs. METHODS: Randomized controlled trials (RCTs),
      quasi-RCTs and control studies evaluating aripiprazole for children with tic
      disorders were identified from PubMed, Embase, Cochrane library, Cochrane
      Central, four Chinese database and relevant reference lists. Quality assessment
      referred to the Cochrane Handbook for Systematic Reviews of Interventions.
      RESULTS: Twelve studies involving 935 participants were included. The general
      quality of included studies was poor. Only one study used placebo as a control
      and others used positive drug controls. Participants were aged between 4 and 18
      years. The period of treatment ranged from 8 to 12 weeks. Seven studies (N = 600
      patients) used the YGTSS scale as the outcome measurement, and there was no
      significant difference in reduction of the total YGTSS score between the
      aripiprazole and positive control groups (MD = -0.48, 95 % CI [-6.22, 5.26], P =
      0.87, I(2) = 87 %). Meta-analysis of four of the studies (N = 285 patients) that
      compared aripiprazole with haloperidol showed that there was no significant
      difference in reduction of the total YGTSS score (MD = 2.50, 95 % CI [-6.93,
      11.92], P = 0.60, I(2) = 88 %). Meta-analysis of two studies (N = 255 patients)
      that compared aripiprazole with tiapride showed that there was no significant
      difference in reduction of the total YGTSS score (MD = -3.15, 95 % CI [-11.38,
      5.09], P = 0.45, I(2) = 86 %). Adverse events (AEs) were reported in 11 studies.
      Drowsiness (5.1 %-58.1 %), increased appetite (3.2 %-25.8 %), nausea (2 %-18.8 %)
      and headache (2 %-16.1 %) were common AEs. CONCLUSION: In conclusion,
      aripiprazole appears to be a promising therapy for children with TDs. Further
      well-conducted RCTs are required to confirm this issue.

PMID- 26220448
TI  - Development of ATAQ-LAM: a tool to assess quality of life in
      Lymphangioleiomyomatosis.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a progressive lung disease that
      impairs health-related quality of life (HRQL). OBJECTIVE: To develop and conduct
      initial testing of ATAQ-LAM (A Tool to Assess Quality of Life in LAM). METHODS: A
      pilot version of the questionnaire was administered to respondents with LAM. We
      used a deletion algorithm to retain items and then applied multi-trait scaling to
      place retained items into appropriate domains, thus generating the ATAQ-LAM.
      Rasch analysis was used to assess item fit to a unidimensional model of HRQL. We
      determined internal consistency (IC) and floor and ceiling effects of ATAQ-LAM
      scores and conducted analyses aimed at supporting the validity of ATAQ-LAM.
      RESULTS: Sixty-nine LAM patients provided response data. Thirty-two items
      survived the deletion algorithm. Scaling suggested ATAQ-LAM should have a four
      domain structure (Exertional dyspnea, IC = 0.94; Cough, IC = 0.91; Fatigue, IC =
      0.91; Emotional Well-Being, IC = 0.89). All items fit the Rasch model. Among 17
      respondents with spirometry within three months of questionnaire completion,
      three of five ATAQ-LAM scores correlated with FEV1% (Exertional Dyspnea: r = 
      0.72, p = 0.001; Fatigue: r = -0.62, p = 0.007 and total: r = -0.53, p = 0.02).
      Compared with those in the highest tertile of FEV1%, subjects in the lowest
      tertile had greater ATAQ-LAM total (121.8 +/- 14.3 vs. 79.8 +/- 13.1, p = 0.04),
      Exertional Dyspnea (54.4 +/- 6.3 vs. 25.5 +/- 5.8, p = 0.005) and Fatigue (2.8 +/
      2.4 vs. 14.8 +/- 2.3, p = 0.03) scores, indicating greater impairment in HRQL.
      CONCLUSIONS: ATAQ-LAM is a disease-specific instrument designed to assess HRQL in
      LAM patients. Additional studies are needed to generate data in support of its
      validity as an instrument capable of assessing HRQL over time in LAM patients.

PMID- 26220449
TI  - Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial
      transcriptional regulators.
AB  - Reversible phosphorylation of bacterial transcriptional regulators (TRs)
      belonging to the family of two-component systems (TCSs) is a well-established
      mechanism for regulating gene expression. Recent evidence points to the fact that
      reversible phosphorylation of bacterial TRs on other types of residue, i.e.
      serine, threonine, tyrosine and cysteine, is also quite common. The
      phosphorylation of the ester type (phospho-serine/threonine/tyrosine) is more
      stable than the aspartate phosphorylation of TCSs. The kinases which catalyse
      these phosphorylation events (Hanks-type serine/threonine protein kinases and
      bacterial protein tyrosine kinases) are also much more promiscuous than the TCS
      kinases, i.e. each of them can phosphorylate several substrate proteins. As a
      consequence, the dynamics and topology of the signal transduction networks
      depending on these kinases differ significantly from the TCSs. Here, we present
      an overview of different classes of bacterial TR phosphorylated and regulated by
      serine/threonine and tyrosine kinases. Particular attention is given to examples
      when serine/threonine and tyrosine kinases interact with TCSs, phosphorylating
      either the histidine kinases or the response regulators. We argue that these
      promiscuous kinases connect several signal transduction pathways and serve the
      role of signal integration. 

PMID- 26220450
TI  - Unintended, but still blameworthy: the roles of awareness, desire, and anger in
      negligence, restitution, and punishment.
AB  - Two experiments (Experiment 1 N = 149, Experiment 2 N = 141) investigated how two
      mental states that underlie how perceivers reason about intentional action
      (awareness of action and desire for an outcome) influence blame and punishment
      for unintended (i.e., negligent) harms, and the role of anger in this process.
      Specifically, this research explores how the presence of awareness (of risk in
      acting, or simply of acting) and/or desire in an acting agent's mental states
      influences perceptions of negligence, judgements that the acting agent owes
      restitution to a victim, and the desire to punish the agent, mediated by anger.
      In both experiments, awareness and desire led to increased anger at the agent and
      increased perception of negligence. Anger mediated the effect of awareness and
      desire on negligence rather than negligence mediating the effect of mental states
      on anger. Anger also mediated punishment, and negligence mediated the effects of
      anger on restitution. We discuss how perceivers consider mental states such as
      awareness, desire, and knowledge when reasoning about blame and punishment for
      unintended harms, and the role of anger in this process.

PMID- 26220451
TI  - In vitro gastrointestinal digestibility of native, hydroxypropylated and cross
      linked wheat starches.
AB  - The digestibility and estimated glycemic indices (GI) of native (NWS), cross
      linked (CLWS) and hydroxypropylated wheat starches (HPWS) were obtained by in
      vitro enzymatic hydrolysis. The resistant starch (RS) content and GI were found
      to be 6.59 and 93.13 for NWS, 7.57 and 92.20 for CLWS, and 13.15 and 89.04 for
      HPWS, respectively. The amounts of glucose release for CLWS were approximately 6
      11%, and for HPWS were 16-19%, lower than that for NWS after digestion under
      simulated intestinal conditions (SIC). The linear and two-term exponential models
      were fitted well to the experimental glucose release data under simulated gastric
      conditions (SGC) and SIC, respectively (R(2) = 0.858-0.991). After digestion
      under SIC, the consistency coefficient (k) values drastically decreased (73.02
      90.27%), while the flow behavior index (n) increased (155.56-363.64%). Therefore,
      the amounts of glucose release can be controlled by manipulating the structure of
      native starches using chemical modifications such as cross-linking and
      hydroxypropylation. 

PMID- 26220454
TI  - Molecular and intermolecular effects in collagen fibril mechanics: a multiscale
      analytical model compared with atomistic and experimental studies.
AB  - Both atomistic and experimental studies reveal the dependence of collagen fibril
      mechanics on biochemical and biophysical features such as, for instance, cross
      link density, water content and protein sequence. In order to move toward a
      multiscale structural description of biological tissues, a novel analytical model
      for collagen fibril mechanics is herein presented. The model is based on a
      multiscale approach that incorporates and couples: thermal fluctuations in
      collagen molecules; the uncoiling of collagen triple helix; the stretching of
      molecular backbone; the straightening of the telopeptide in which covalent cross
      links form; slip-pulse mechanisms due to the rupture of intermolecular weak
      bonds; molecular interstrand delamination due to the rupture of intramolecular
      weak bonds; the rupture of covalent bonds within molecular strands. The
      effectiveness of the proposed approach is verified by comparison with available
      atomistic results and experimental data, highlighting the importance of cross
      link density in tuning collagen fibril mechanics. The typical three-region shape
      and hysteresis behavior of fibril constitutive response, as well as the
      transition from a yielding-like to a brittle-like behavior, are recovered with a
      special insight on the underlying nanoscale mechanisms. The model is based on
      parameters with a clear biophysical and biochemical meaning, resulting in a
      promising tool for analyzing the effect of pathological or pharmacological
      induced histochemical alterations on the functional mechanical response of
      collagenous tissues. 

PMID- 26220453
TI  - Poromicromechanics reveals that physiological bone strains induce osteocyte
      stimulating lacunar pressure.
AB  - Mechanical loads which are macroscopically acting onto bony organs, are known to
      influence the activities of biological cells located in the pore spaces of bone,
      in particular so the signaling and production processes mediated by osteocytes.
      The exact mechanisms by which osteocytes are actually able to "feel" the
      mechanical loading and changes thereof, has been the subject of numerous studies,
      and, while several hypotheses have been brought forth over time, this topic has
      remained a matter of debate. Relaxation times reported in a recent experimental
      study of Gardinier et al. (Bone 46(4):1075-1081, 2010) strongly suggest that the
      lacunar pores are likely to experience, during typical physiological load cycles,
      not only fluid transport, but also undrained conditions. The latter entail the
      buildup of lacunar pore pressures, which we here quantify by means of a thorough
      multiscale modeling approach. In particular, the proposed model is based on
      classical poroelasticity theory, and able to account for multiple pore spaces.
      First, the model reveals distinct nonlinear dependencies of the resulting lacunar
      (and vascular) pore pressures on the underlying bone composition, highlighting
      the importance of a rigorous multiscale approach for appropriate computation of
      the aforementioned pore pressures. Then, the derived equations are evaluated for
      macroscopic (uniaxial as well as hydrostatic) mechanical loading of physiological
      magnitude. The resulting model-predicted pore pressures agree very well with the
      pressures that have been revealed, by means of in vitro studies, to be of
      adequate magnitude for modulating the responses of biological cells, including
      osteocytes. This underlines that osteocytes may respond to many types of loading
      stimuli at the same time, in particular so to fluid flow and hydrostatic
      pressure. 

PMID- 26220456
TI  - Biological Perspectives: Anti-NMDA Receptor Encephalitis.
AB  - PURPOSE: This article explores the recently recognized anti-NMDA receptor
      encephalitis, which may produce psychiatric symptoms. CONCLUSIONS: Historically,
      some patients presenting for psychiatric care may have actually been suffering
      from anti-NMDA encephalitis; thus, awareness of this disorder may facilitate
      appropriate treatment. TREATMENT IMPLICATIONS: Early diagnosis and aggressive
      treatment promote better outcomes. First-line treatment includes immunotherapy.

PMID- 26220455
TI  - Adaptation of active tone in the mouse descending thoracic aorta under acute
      changes in loading.
AB  - Arteries can adapt to sustained changes in blood pressure and flow, and it is
      thought that these adaptive processes often begin with an altered smooth muscle
      cell activity that precedes any detectable changes in the passive wall
      components. Yet, due to the intrinsic coupling between the active and passive
      properties of the arterial wall, it has been difficult to delineate the adaptive
      contributions of active smooth muscle. To address this need, we used a novel
      experimental-computational approach to quantify adaptive functions of active
      smooth muscle in arterial rings excised from the proximal descending thoracic
      aorta of mice and subjected to short-term sustained circumferential stretches
      while stimulated with various agonists. A new mathematical model of the adaptive
      processes was derived and fit to data to describe and predict the effects of
      active tone adaptation. It was found that active tone was maintained when the
      artery was adapted close to the optimal stretch for maximal active force
      production, but it was reduced when adapted below the optimal stretch; there was
      no significant change in passive behavior in either case. Such active adaptations
      occurred only upon smooth muscle stimulation with phenylephrine, however, not
      stimulation with KCl or angiotensin II. Numerical simulations using the proposed
      model suggested further that active tone adaptation in vascular smooth muscle
      could play a stabilizing role for wall stress in large elastic arteries.

PMID- 26220457
TI  - Suicidal tendencies as correlates of disability measures.
AB  - Disabilities and handicaps affect health-related quality-of-life (HRQOL) and
      dysphoria symptoms (helpless, hopeless, worthless, dissatisfied with life,
      depressed, suicidal). Archived 2009 Canadian Community Health Survey (CCHS) data
      (N=124,188) replicated 49 positive correlations (p<.001) of seven kinds of
      disability measured by the Health Utilities Index (HUI) with seven measures of
      dysphoria. Cognition and pain disabilities appeared most dysphoric. Individuals
      (N=724) in the 2009 CCHS data with HUI total scores less than 0.00 are defined by
      HUI protocols as "worse than dead." This HUI categorization has doubtful validity
      based on 17 measures of disability, suicidality, self-perceived health, and
      social engagement.

PMID- 26220459
TI  - Stigmatizing the other: An exploratory study of unintended consequences of eating
      disorder public service announcements.
AB  - This research explores the intended and unintended consequences of eating
      disorder public service announcements. We assessed participants' attitudes toward
      eating disorders and people with eating disorders, willingness to interact with
      people with eating disorders, and experience with eating disorders (covariate) at
      Time 1. At Time 2, participants were randomly assigned to watch a stigmatizing or
      a non-stigmatizing eating disorder public service announcement. Exposure to the
      stigmatizing public service announcement resulted in more negative attitudes
      toward eating disorders and in less willingness to interact with people with
      eating disorders, but not in significantly more negative attitudes toward people
      with eating disorders. The discussion highlights the practical implications for
      health communication campaigns.

PMID- 26220458
TI  - Coping strategies and health-related quality of life after stroke.
AB  - Cerebral stroke causes a significant worsening of health-related quality of life.
      This review was conducted on studies investigating whether the levels of quality
      of life were influenced by the coping strategies used by stroke patients. We
      searched on PubMed and Web of Science databases and screening references of
      included studies and review articles for additional citations. From initial 389
      publications, we included only 6 studies that met search criteria and described
      the association between coping and quality of life. Results showed that patients
      who prefer accommodative or active coping strategies had a better quality of life
      after stroke when compared with patients who adopted assimilative coping.

PMID- 26220460
TI  - When healthcare professionals cannot do the right thing: A systematic review of
      moral distress and its correlates.
AB  - Moral distress occurs when professionals cannot carry out what they believe to be
      ethically appropriate actions. This review describes the publication trend on
      moral distress and explores its relationships with other constructs. A
      bibliometric analysis revealed that since 1984, 239 articles were published, with
      an increase after 2011. Most of them (71%) focused on nursing. Of the 239
      articles, 17 empirical studies were systematically analyzed. Moral distress
      correlated with organizational environment (poor ethical climate and
      collaboration), professional attitudes (low work satisfaction and engagement),
      and psychological characteristics (low psychological empowerment and autonomy).
      Findings revealed that moral distress negatively affects clinicians' wellbeing
      and job retention. Further studies should investigate protective psychological
      factors to develop preventive interventions.

PMID- 26220461
TI  - Using distant supervised learning to identify protein subcellular localizations
      from full-text scientific articles.
AB  - Databases of curated biomedical knowledge, such as the protein-locations
      reflected in the UniProtKB database, provide an accurate and useful resource to
      researchers and decision makers. Our goal is to augment the manual efforts
      currently used to curate knowledge bases with automated approaches that leverage
      the increased availability of full-text scientific articles. This paper describes
      experiments that use distant supervised learning to identify protein subcellular
      localizations, which are important to understand protein function and to identify
      candidate drug targets. Experiments consider Swiss-Prot, the manually annotated
      subset of the UniProtKB protein knowledge base, and 43,000 full-text articles
      from the Journal of Biological Chemistry that contain just under 11.5 million
      sentences. The system achieves 0.81 precision and 0.49 recall at sentence level
      and an accuracy of 57% on held-out instances in a test set. Moreover, the
      approach identifies 8210 instances that are not in the UniProtKB knowledge base.
      Manual inspection of the 50 most likely relations showed that 41 (82%) were
      valid. These results have immediate benefit to researchers interested in protein
      function, and suggest that distant supervision should be explored to complement
      other manual data curation efforts. 

PMID- 26220463
TI  - The effects of extrinsic stress on somatic markers and behavior are dependent on
      animal housing conditions.
AB  - Properties of the environment play an important role in animal wellbeing and may
      modulate the effects of external threats. Whereas stressors can affect emotion
      and impair cognition, environmental enrichment may prevent the occurrence of such
      negative sequelae. Animals exposed to semi-natural group-housing experience a
      complex environment; whereas environmental enrichment might protect against
      stressors, a socially-enriched environment(SEE) could entail aggressive inter
      male encounters with additive stress effects. In the present study, we
      investigated the effects of exposure to external stressors, footshocks and forced
      swimming, on adrenal gland and body weights as well as on behavior in rats housed
      under SEE or standard, non-enriched environment (NEE), conditions. We found that
      SEEs reduced the anxiogenic effects of stress. Moreover, SEEs improved the
      performance in an operant task and prevented the increase in impulsive behavior
      produced by external stressors on NEE animals. Whereas these findings are
      indicative of stress-buffering effects of SEEs, adrenal gland weights were
      increased while total body weights were decreased in SEE rats, suggesting that
      SEEs may simultaneously exacerbate physiological measurements of stress. Finally,
      in the SEE, total aggressive behaviors and body wounds were paradoxically reduced
      in animals that received external stressors in comparison to non-stressed
      controls. The consequences of the external stressors applied here are not
      uniform, varying according to the housing condition and the outcome considered. 

PMID- 26220464
TI  - Dopamine D1 and opioid receptor antagonists differentially reduce the acquisition
      and expression of fructose-conditioned flavor preferences in BALB/c and SWR mice.
AB  - Sugar appetite is influenced by unlearned and learned preferences in rodents. The
      present study examined whether dopamine (DA) D1 (SCH23390: SCH) and opioid
      (naltrexone: NTX) receptor antagonists differentially altered the expression and
      acquisition of fructose-conditioned flavor preferences (CFPs) in BALB/c and SWR
      mice. In expression experiments, food-restricted mice alternately (10 sessions,
      1h) consumed a flavored (e.g., cherry) 8% fructose+0.2% saccharin solution (CS+)
      and a differently-flavored (e.g., grape) 0.2% saccharin solution (CS-). Two
      bottle CS choice tests (1h) occurred 0.5h following vehicle: SCH (200 or 800
      nmol/kg) or NTX (1 or 5mg/kg). SCH, but not NTX significantly reduced CS+
      preference in both strains. In acquisition experiments, 0.5h prior to 10
      acquisition training sessions, vehicle, SCH (50 nmol/kg), NTX (1 mg/kg) or
      Limited Control vehicle treatments were administered, followed by two-bottle CS
      choice tests without injections. SCH and NTX reduced training intakes in both
      strains. BALB/c mice displayed hastened extinction of the fructose-CFP following
      training with SCH, but not NTX. SCH eliminated fructose-CFP acquisition in SWR
      mice, whereas NTX hastened extinction of the CFP. These results are compared to
      previous drug findings obtained with sucrose-CFPs in SWR and BALB/c mice, and are
      discussed in terms of differential effects of these sugars on oral and post-oral
      conditioning.

PMID- 26220465
TI  - Eight-month test-retest agreement in morning salivary cortisol, self- and parent
      rated anxiety in boys with an Autism Spectrum Disorder.
AB  - The agreement over time in morning salivary cortisol concentrations and also self
      and parent-rated anxiety was investigated in a sample of 16 boys with an ASD.
      Cortisol and anxiety data were collected eight months apart. Results indicated
      that there were significant correlations between each pair of measures from the
      two occasions, suggesting that cortisol concentrations and anxiety did not vary
      much at all over that time, challenging the assumption that cortisol needs to be
      measured over multiple days to obtain reliable data from children with an ASD.
      Implications for research into the ways these children respond to chronic
      stressors are discussed. 

PMID- 26220466
TI  - Functional MRI cortical activations from unilateral tactile-taste stimulations of
      the tongue.
AB  - Functional magnetic resonance imaging (fMRI) was used for revealing activations
      in the human brain by lateralized tactile-gustatory stimulations of the tongue.
      Salt, a basic taste stimulus, and water, now recognized as an independent taste
      modality, were applied to either hemitongues with pads similar to the taste
      strips test for the clinical psychophysical evaluation of taste. With both
      stimuli, the observed cortical patterns of activations could be attributed to a
      combined somatosensory and gustatory stimulation of the tongue, with no
      significant differences between salt and water. Stimulation of each hemitongue
      evoked a bilateral activation of the anterior insula-frontal operculum,
      ascribable to the gustatory component of the stimulation, and a bilateral
      activation of the inferior part of the postcentral gyrus, ascribable to the
      tactile component of the stimulation. The results are in line with the notion
      that the representation of the tongue in the cerebral hemispheres in both the
      touch and the taste modalities is bilateral. Clinical and brain stimulation
      findings indicate that this bilaterality depends primarily on a partial crossing
      of the afferent pathways, perhaps with a predominance of the crossed pathway in
      the touch modality and the uncrossed pathway in the taste modality. Previous
      evidence suggests that the corpus callosum is not indispensible for this
      bilateral representation, but can contribute to it by interhemispheric transfer
      of information in both modalities. 

PMID- 26220467
TI  - Buccal swab as a reliable predictor for X inactivation ratio in inaccessible
      tissues.
AB  - BACKGROUND: As a result of the epigenetic phenomenon of X chromosome inactivation
      (XCI) every woman is a mosaic of cells with either an inactive paternal X
      chromosome or an inactive maternal X chromosome. The ratio between inactive
      paternal and maternal X chromosomes is different for every female individual, and
      can influence an X-encoded trait or disease. A multitude of X linked conditions
      is known, and for many of them it is recognised that the phenotype in affected
      female carriers of the causative mutation is modulated by the XCI ratio. To
      predict disease severity an XCI ratio is usually determined in peripheral blood
      samples. However, the correlation between XCI ratios in peripheral blood and
      disease affected tissues, that are often inaccessible, is poorly understood.
      Here, we tested several tissues obtained from autopsies of 12 female individuals
      for patch size and XCI ratio. METHODS: XCI ratios were analysed using methyl
      sensitive PCR-based assays for the AR, PCSK1N and SLITRK4 loci. XCI patch size
      was analysed by testing the XCI ratio of tissue samples with decreasing size.
      RESULTS: XCI patch size was analysed for liver, muscle, ovary and brain samples
      and was found too small to confound testing for XCI ratio in these tissues. XCI
      ratios were determined in the easily accessible tissues, blood, buccal epithelium
      and hair follicle, and compared with ratios in several inaccessible tissues.
      CONCLUSIONS: Buccal epithelium is preferable over peripheral blood for predicting
      XCI ratios of inaccessible tissues. Ovary is the only inaccessible tissue showing
      a poor correlation to blood and buccal epithelium, but has a good correlation to
      hair follicle instead.

PMID- 26220468
TI  - Anti-psoriatic effects of Honokiol through the inhibition of NF-kappaB and VEGFR
      2 in animal model of K14-VEGF transgenic mouse.
AB  - Honokiol (HK), a biphenolic neolignan isolated from Magnolia officinalis, has
      been reported to possess anti-inflammatory and anti-angiogenic activaties. In
      this study, our aim was to investigate anti-psoriatic activities of HK and the
      involved mechanisms. In vitro, the effects of HK on the regulation of Th1/Th2 and
      TNF-alpha-induced NF-kappaB (p65) activation were analyzed by respective FCS and
      immunofluorescence. Additionally, the K14-VEGF transgenic model was used for the
      in vivo study. ELISA and Q-PCR were performed to evaluate serum levels of Th1/Th2
      cytokines and their corresponding mRNA expressions. Effects on VEGFR-2 and p65
      activation, as well as other angiogenic and inflammatory parameters were studied
      by immunostainings. Importantly, we found that HK significantly decreased the
      ratio of Th1/Th2-expression CD4(+) T cells and inhibited TNF-alpha-induced
      activation of NF-kappaB. The morphology and histological features of psoriasis
      were effectively improved by HK treatment. The expression of TNF-alpha and IFN
      gamma, and their corresponding mRNA levels were down-regulated and the expression
      of nuclear p65, VEGFR-2, as well as related phosphorylated proteins (p-VEGFR-2, p
      ERK1/2, p-AKT and p-p38) were also suppressed. Overall, these results in our
      study suggested that HK exhibits anti-psoriatic effects through the inhibition of
      NF-kappaB and VEGFR-2. 

PMID- 26220469
TI  - Impact of subclinical and clinical mastitis on sensitivity to pain of dairy cows.
AB  - A total of 90 cows from three commercial farms were used to evaluate the
      relationship between subclinical mastitis and clinical mastitis and thermal
      nociceptive threshold. Milk strips from all udder quarters were tested for
      clinical mastitis with visual inspection of milk and udder alterations and for
      subclinical mastitis using California Mastitis Test. Milk yield was recorded,
      milk was sampled and further analyzed for somatic cells count (SCC). Cows were
      considered healthy when SCC200 000 cells/ml and no visual alterations in milk
      and/or udder, with moderate subclinical mastitis when SCC>500 000 cells/ml and no
      visual alterations in milk and/or udder and with clinical mastitis when visual
      alterations in milk and/or udder were detected. Nociceptive threshold was
      evaluated with the thermal threshold meter apparatus applied to the rear legs.
      Thermal threshold (TT) decreased when we compared healthy cows with cows
      presenting clinical mastitis and tended to decrease when we compare healthy cows
      with those with moderate subclinical mastitis. TT was lower at the ipsilateral
      rear leg compared with the contralateral leg to the infected mammary gland. TT
      linearly decreases as log10SCC increased and it showed sharp decrease as log10SCC
      exceed the value of 6.4. Increase in one unit of log10SCC increased the odds of
      low thermal threshold (lower than 55.8 degrees C). Subclinical mastitis might be
      a welfare issue as it tended to decrease nociceptive thermal threshold. 

PMID- 26220470
TI  - Study of the Binding Energies between Unnatural Amino Acids and Engineered
      Orthogonal Tyrosyl-tRNA Synthetases.
AB  - We utilized several computational approaches to evaluate the binding energies of
      tyrosine (Tyr) and several unnatural Tyr analogs, to several orthogonal aaRSes
      derived from Methanocaldococcus jannaschii and Escherichia coli tyrosyl-tRNA
      synthetases. The present study reveals the following: (1) AutoDock Vina and
      ROSETTA were able to distinguish binding energy differences for individual pairs
      of favorable and unfavorable aaRS-amino acid complexes, but were unable to
      cluster together all experimentally verified favorable complexes from unfavorable
      aaRS-Tyr complexes; (2) MD-MM/PBSA provided the best prediction accuracy in terms
      of clustering favorable and unfavorable enzyme-substrate complexes, but also
      required the highest computational cost; and (3) MM/PBSA based on single energy
      minimized structures has a significantly lower computational cost compared to MD
      MM/PBSA, but still produced sufficiently accurate predictions to cluster aaRS
      amino acid interactions. Although amino acid-aaRS binding is just the first step
      in a complex series of processes to acylate a tRNA with its corresponding amino
      acid, the difference in binding energy, as shown by MD-MM/PBSA, is important for
      a mutant orthogonal aaRS to distinguish between a favorable unnatural amino acid
      (unAA) substrate from unfavorable natural amino acid substrates. Our
      computational study should assist further designing and engineering of orthogonal
      aaRSes for the genetic encoding of novel unAAs. 

PMID- 26220472
TI  - A novel synthetic route towards monodisperse LaOF:Ln3+ (Ln = Eu, Tb) hollow
      spheres with multicolor luminescence properties.
AB  - In this study, monodisperse and uniform LaOF hollow spheres were successfully
      synthesized through a novel facile synthetic route employing a La(OH)CO3 sphere
      as a sacrificial template followed by a subsequent calcination process. The
      structure, morphology, formation process, and luminescence properties were well
      investigated using various techniques. The possible formation mechanism of
      evolution from the La(OH)CO3 spheres to the LaCO3F precursor, and to the final
      LaOF hollow spheres can be attributed to the Kirkendall effect and the
      decomposition of the LaCO3F precursor. Under ultraviolet excitation, the
      LaOF:Ln(3+) (Ln = Eu,Tb) hollow spheres show their characteristic f-f emissions
      and exhibit red, green emissions, respectively. Moreover, by codoping the Tb(3+)
      and Eu(3+) ions into the LaOF host and tuning their relative concentration ratio,
      multicolor tunable emissions are obtained due to the efficient energy transfer
      from Tb(3+) to Eu(3+) at 378 nm excitation. This material may find potential
      application in color display fields. 

PMID- 26220471
TI  - Evaluation of variant detection software for pooled next-generation sequence
      data.
AB  - BACKGROUND: Despite the tremendous drop in the cost of nucleotide sequencing in
      recent years, many research projects still utilize sequencing of pools containing
      multiple samples for the detection of sequence variants as a cost saving measure.
      Various software tools exist to analyze these pooled sequence data, yet little
      has been reported on the relative accuracy and ease of use of these different
      programs. RESULTS: In this manuscript we evaluate five different variant
      detection programs-The Genome Analysis Toolkit (GATK), CRISP, LoFreq, VarScan,
      and SNVer-with regard to their ability to detect variants in synthetically pooled
      Illumina sequencing data, by creating simulated pooled binary alignment/map (BAM)
      files using single-sample sequencing data from varying numbers of previously
      characterized samples at varying depths of coverage per sample. We report the
      overall runtimes and memory usage of each program, as well as each program's
      sensitivity and specificity to detect known true variants. CONCLUSIONS: GATK,
      CRISP, and LoFreq all gave balanced accuracy of 80% or greater for datasets with
      varying per-sample depth of coverage and numbers of samples per pool. VarScan and
      SNVer generally had balanced accuracy lower than 80%. CRISP and LoFreq required
      up to four times less computational time and up to ten times less physical memory
      than GATK did, and without filtering, gave results with the highest sensitivity.
      VarScan and SNVer had generally lower false positive rates, but also
      significantly lower sensitivity than the other three programs.

PMID- 26220473
TI  - Rosiglitazone attenuates early brain injury after experimental subarachnoid
      hemorrhage in rats.
AB  - Early brain injury (EBI) plays a crucial role in the pathological progress of
      subarachnoid hemorrhage (SAH). This study was designed to determine whether
      rosiglitazone protects the brain against EBI in rats, and discuss the role of the
      anti-apoptotic mechanism mediated by Bcl-2 family proteins in this
      neuroprotection. 86 male Sprague-Dawley rats were divided into the sham group,
      the SAH+ vehicle group and the SAH+ rosiglitazone group. SAH was induced via an
      endovascular perforation technique and rosiglitazone (3mg/kg) or vehicle was
      administered. Mortality, neurological scores, brain water content, Evans blue dye
      assay, TUNEL stain assay, Gelatin zymography, and western blot analysis were
      performed. Rosiglitazone significantly improved mortality, neurological scores,
      brain water content, blood brain barrier (BBB) and apoptosis compared with the
      vehicle group within 24h after SAH. The TUNEL staining assay demonstrated that
      apoptosis was ameliorated. Cleaved Caspase-3 and MMP-9 expression was reduced,
      whereas Bcl-2 and p-Bad was markedly preserved by rosiglitazone. A significant
      elevation of p-Akt was detected after rosiglitazone treatment. Our study
      demonstrated that rosiglitazone plays a neuroprotective role in EBI after SAH via
      attenuation of BBB disruption, brain edema and apoptosis. 

PMID- 26220474
TI  - Protection of the brain following cerebral ischemia through the attenuation of
      PARP-1-induced neurovascular unit damage in rats.
AB  - Cerebral ischemia is a major health crisis throughout the world, and the
      currently available thrombolytic therapy is unsatisfactory. Cell death following
      cerebral ischemia is mediated by a complex pathophysiological interaction of
      various mechanisms. During an ischemic insult, not only neurons but all of the
      components of the neurovascular unit, such as glia, endothelia, pericytes and
      basal membranes, are destroyed. Previous studies have shown that excessive
      stimulation of poly (ADP-ribose) polymerase (PARP-1) is crucial for cerebral
      injury after ischemic insult, which is an important cause of cell death in all
      cell types within the neurovascular unit. To investigate whether PARP-1 plays an
      important role in protecting the neurovascular unit following cerebral ischemia,
      we evaluated neurobehavioral deficits, PARP-1 activity, blood brain barrier (BBB)
      disruption and neurovascular unit deficits using Western blot analysis, TTC
      staining and electron microscopy in an MCAO rat model. The results revealed that
      PARP-1 enzymatic activity was dramatically increased after ischemia. Inhibition
      of PARP-1 significantly reduced the extent of both cerebral infarction and edema,
      improved neurological scores, and attenuated the damage to the neurovascular unit
      in cerebral ischemia. Collectively, these findings demonstrate that the down
      regulation of PARP-1 activity contributes to reducing post-ischemic brain damage
      via protection of the neurovascular unit. 

PMID- 26220475
TI  - Gene-environment interactions in esophageal cancer.
AB  - Esophageal cancer (EC) is one of the most common malignancies in low- and medium
      income countries and represents a disease of public health importance because of
      its poor prognosis and high mortality rate in these regions. The striking
      variation in the prevalence of EC among different ethnic groups suggests a
      significant contribution of population-specific environmental and dietary factors
      to susceptibility to the disease. Although individuals within a demarcated
      geographical area are exposed to the same environment and share similar dietary
      habits, not all of them will develop the disease; thus genetic susceptibility to
      environmental risk factors may play a key role in the development of EC. A wide
      range of xenobiotic-metabolizing enzymes are responsible for the metabolism of
      carcinogens introduced via the diet or inhaled from the environment. Such dietary
      or environmental carcinogens can bind to DNA, resulting in mutations that may
      lead to carcinogenesis. Genes involved in the biosynthesis of these enzymes are
      all subject to genetic polymorphisms that can lead to altered expression or
      activity of the encoded proteins. Genetic polymorphisms may, therefore, act as
      molecular biomarkers that can provide important predictive information about
      carcinogenesis. The aim of this review is to discuss our current knowledge on the
      genetic risk factors associated with the development of EC in different
      populations; it addresses mainly the topics of genetic polymorphisms, gene
      environment interactions, and carcinogenesis. We have reviewed the published data
      on genetic polymorphisms of enzymes involved in the metabolism of xenobiotics and
      discuss some of the potential gene-environment interactions underlying esophageal
      carcinogenesis. The main enzymes discussed in this review are the glutathione S
      transferases (GSTs), N-acetyltransferases (NATs), cytochrome P450s (CYPs),
      sulfotransferases (SULTs), UDP-glucuronosyltransferases (UGTs), and epoxide
      hydrolases (EHs), all of which have key roles in the detoxification of
      environmental and dietary carcinogens. Finally, we discuss recent advances in the
      study of genetic polymorphisms associated with EC risk, specifically with regard
      to genome-wide association studies, and examine possible challenges of case
      control studies that need to be addressed to better understand the interaction
      between genetic and environmental factors in esophageal carcinogenesis. 

PMID- 26220476
TI  - Chaperonin containing T-complex polypeptide subunit eta is a potential marker of
      joint contracture: an experimental study in the rat.
AB  - Joint contracture is a fibroproliferative disorder that restricts joint mobility,
      resulting in tissue degeneration and deformity. However, the etiology of joint
      contracture is still unknown. Chaperonin containing T-complex polypeptide subunit
      eta (CCT-eta) is reported to increase in fibrotic diseases. The purpose of this
      study was to investigate whether CCT-eta is implicated in joint contracture and
      to determine the role of CCT-eta in the progression of joint contracture by
      analyzing a rat model. We immobilized the left knee joint of rat by internal
      fixation for 8 weeks. The non-immobilized right leg served as a control. The
      range of motion (ROM) of the knee was investigated. Fibroblasts were obtained
      from the posterior joint capsule of the joints. The outcome was followed by
      quantitative real-time polymerase chain reaction (qRT-PCR), Western blot,
      fibroblast migration assay, and collagen assay. The effect of CCT-eta on the
      functions of fibroblasts was observed by utilizing a short inhibitory RNA (siRNA)
      targeting CCT-eta. The ROM of the immobilized joints was significantly limited
      compared to the contralateral joints (p < 0.05). Fibroblasts derived from the
      contractive joints showed higher mRNA and protein expressions of CCT-eta in
      parallel with alpha-smooth muscle actin (alpha-SMA) compared to the cells from
      the contralateral knees (p < 0.05). siRNA-mediated downregulation of CCT-eta
      inhibited the expressions of both CCT-eta and alpha-SMA. Moreover, the reduction
      of CCT-eta also significantly decreased fibroblast functions such as cell
      mobility and collagen synthesis (all p < 0.05). Our findings indicate that CCT
      eta appears to be a potential marker of joint contracture disease.

PMID- 26220477
TI  - Transgenic mouse models generated by hydrodynamic transfection for genetic
      studies of liver cancer and preclinical testing of anti-cancer therapy.
AB  - Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide;
      however, the genetic mechanisms underlying its pathogenesis are incompletely
      understood. Genetically engineered mouse (GEM) models of HCC have been developed
      to elucidate the role of individual cancer-related genes in hepatocarcinogenesis.
      However, the expensive and time-consuming processes related to generating a GEM
      model discourage the development of diverse genotype models. Recently, a simple
      and inexpensive liver-specific transgenic approach was developed, in which a
      hydrodynamics-based transfection (HT) method was coupled with the Sleeping Beauty
      transposase system. Various HT models in which different oncogenic pathways are
      activated and/or tumor-suppressing pathways inactivated have been developed in
      recent years. The applicability of HT models in liver cancer research is expected
      to broaden and ultimately elucidate the cooperation between oncogenic signaling
      pathways and aid in designing molecular therapy to target altered pathways. 

PMID- 26220479
TI  - Pleiotropic effects of amino acid substitutions in H5 hemagglutinin of influenza
      A escape mutants.
AB  - We believe that the monitoring of pleiotropic effects of the hemagglutinin (HA)
      mutations found in H5 escape mutants is essential for accurate prediction of
      mutants with pandemic potential. In the present study, we assessed multiple
      characteristics of antibody-selected HA mutations. We examined the pH optimum of
      fusion, HA heat inactivation, affinity to sialyl receptors, and in vitro and in
      vivo replication kinetics of various influenza H5 escape mutants. Several amino
      acid substitutions, including T108I, K152E, R162G, and K218N, reduced the
      stability of HA as determined by heat inactivation, whereas S128L and T215A
      substitutions were associated with significant increases in HA thermostability
      compared to the respective wild-type viruses. HA mutations at positions 108, 113,
      115, 121, 123, 128, 162, and 190 and substitutions at positions 123, 199, and 215
      affected the replicative ability of H5 escape mutants in vitro and in vivo,
      respectively. The T108I substitution lowered the pH optimum of fusion and HA
      temperature stability while increasing viral replicative ability. Taken together,
      a co-variation between antigenic specificity and different HA phenotypic
      properties has been demonstrated. 

PMID- 26220480
TI  - Detection of different South American hantaviruses.
AB  - Hantaviruses are the etiologic agents of Hemorrhagic Fever with Renal Syndrome
      (HFRS) in Old World, and Hantavirus Pulmonary Syndrome (HPS)/Hantavirus
      Cardiopulmonary Syndrome (HCPS), in the New World. Serological methods are the
      most common approach used for laboratory diagnosis of HCPS, however theses
      methods do not allow the characterization of viral genotypes. The polymerase
      chain reaction (PCR) has been extensively used for diagnosis of viral infections,
      including those caused by hantaviruses, enabling detection of few target sequence
      copies in the sample. However, most studies proposed methods of PCR with species
      specific primers. This study developed a simple and reliable diagnostic system by
      RT-PCR for different hantavirus detection. Using new primers set, we evaluated
      human and rodent hantavirus positive samples of various regions from Brazil.
      Besides, we performed computational analyzes to evaluate the detection of other
      South American hantaviruses. The diagnostic system by PCR proved to be a sensible
      and simple assay, allowing amplification of Juquitiba virus, Araraquara virus,
      Laguna Negra virus, Rio Mamore virus and Jabora virus, beyond of the possibility
      of the detecting Andes, Anajatuba, Bermejo, Choclo, Cano Delgadito, Lechiguanas,
      Maciel, Oran, Pergamino and Rio Mearim viruses. The primers sets designed in this
      study can detect hantaviruses from almost all known genetics lineages in Brazil
      and from others South America countries and also increases the possibility to
      detect new hantaviruses. These primers could easily be used both in diagnosis of
      suspected hantavirus infections in humans and also in studies with animals
      reservoirs. 

PMID- 26220481
TI  - Neuropharmacology: Pain relief without pairing up.

PMID- 26220482
TI  - Neurodegeneration: Reelin' from loss.

PMID- 26220478
TI  - Development and applications of single-cycle infectious influenza A virus
      (sciIAV).
AB  - The diverse host range, high transmissibility, and rapid evolution of influenza A
      viruses justify the importance of containing pathogenic viruses studied in the
      laboratory. Other than physically or mechanically changing influenza A virus
      containment procedures, modifying the virus to only replicate for a single round
      of infection similarly ensures safety and consequently decreases the level of
      biosafety containment required to study highly pathogenic members in the virus
      family. This biological containment is more ideal because it is less apt to
      computer, machine, or human error. With many necessary proteins that can be
      deleted, generation of single-cycle infectious influenza A viruses (sciIAV) can
      be achieved using a variety of approaches. Here, we review the recent burst in
      sciIAV generation and summarize the applications and findings on this important
      human pathogen using biocontained viral mimics. 

PMID- 26220483
TI  - Organic acids, amino acids compositions in the root exudates and Cu-accumulation
      in castor (Ricinus communis L.) Under Cu stress.
AB  - Ricinus communis L. is a hyperaccumulation plant newly discovered in an abandoned
      land of Cu mine in China. A hydroponic experiment was then carried out to
      determine the root exudates in the Cu-tolerant castor (Ricinus communis L.).
      Plants were grown in nutrient solution with increasing level of Cu doses (0, 100,
      250, 500, and 750 MUmol/L Cu) in the form of CuSO4. Cu accumulation in the roots
      and shoots of castor, and root exudates collected from the castor were measured.
      The results indicated that the castor had a high Cu accumulation capacity and the
      Cu concentrations in the shoots and roots of the castor treated with 750 MUmol/L
      Cu were 177.1, 14586.7 mg/kg, respectively. Tartaric was the largest in the root
      exudates in terms of concentrations, which reached up to 329.13 MUmol/g (dry
      plant) in the level of 750 MUmol/L Cu. There was a significantly positive linear
      relationship between the Cu concentration in root and the concentration of
      succinic (R = 0.92, P < 0.05), tartaric (R = 0.96, P < 0.01), and citric (R =
      0.89, P < 0.05). These results indicated that the difference in root exudation
      from castor could affect their Cu tolerance. What is more, significant is that
      the high tartaric and citric, the low oxalic and cysteine in the root exudation
      of castor contributed to toleration of high Cu concentrations. 

PMID- 26220484
TI  - Re: "Is the Inverse Association Between Selenium and Bladder Cancer Due to
      Confounding by Smoking?".

PMID- 26220496
TI  - Lichen scrofulosorum: yet another disease manifesting the Koebner phenomenon?

PMID- 26220497
TI  - Socioeconomic Status, Alcohol Use, and Pregnancy Intention in a National Sample
      of Women.
AB  - Using data from the 2004 and 2006 Behavioral Risk Factor Surveillance System
      (BRFSS), a cross-sectional study was conducted to explore the role of
      socioeconomic status as a potential modifier on the relationship between a
      woman's intention to become pregnant and her drinking behaviors. The analytic
      sample included 37,777 fertile women aged 18-44 years. The primary outcomes were
      any, heavy, or binge drinking. The analysis included three separate multivariable
      logistic regression models to account for the complex survey methodology utilized
      in the BRFSS. In the unadjusted models, women intending a pregnancy were less
      likely to drink at heavy (OR = 0.68, CI = 0.50, 0.93) or binge (OR = 0.80, CI =
      0.67, 0.96) levels compared to those not intending a pregnancy. Adjusted
      regression models indicated that both education and income modified the relation
      between pregnancy intention and any drinking and binge drinking. After performing
      a multivariable regression model stratified by education, women who had more than
      a high school education and were intending to become pregnant were 28 % less
      likely to binge drink than those not intending a pregnancy (OR = 0.72, CI = 0.57,
      0.90). Stratification by income indicated that women intending to become pregnant
      within the middle income categories were less likely to drink any alcohol
      compared to those not intending a pregnancy. Pregnancy intention and binge
      drinking were associated among women with more than a high school education, with
      those intending a pregnancy being less likely to binge drink. Generally, as
      education increased, the association between income and binge drinking weakened.

PMID- 26220498
TI  - The impact of El Nino events on the pelagic food chain in the northern California
      Current.
AB  - The zooplankton of the northern California Current are typically characterized by
      an abundance of lipid-rich copepods that support rapid growth and survival of
      ecologically, commercially, and recreationally valued fish, birds, and mammals.
      Disruption of this food chain and reduced ecosystem productivity are often
      associated with climatic variability such as El Nino events. We examined the
      variability in timing, magnitude, and duration of positive temperature anomalies
      and changes in copepod species composition in the northern California Current in
      relation to 10 tropical El Nino events. Measurable impacts on mesozooplankton of
      the northern California Current were observed during seven of 10 of these events.
      The occurrence of anomalously warm water and the response of the copepod
      community was rapid (lag of zero to 2 months) following the initiation of
      canonical Eastern Pacific (EP) events, but delayed (lag of 2-8 months) following
      'Modoki' Central Pacific (CP) events. The variable lags in the timing of a
      physical and biological response led to impacts in the northern California
      Current peaking in winter during EP events and in the spring during CP events.
      The magnitude and duration of the temperature and copepod anomalies were strongly
      and positively related to the magnitude and duration of El Nino events, but were
      also sensitive to the phase of the lower frequency Pacific Decadal Oscillation.
      When fisheries managers and biological oceanographers are faced with the prospect
      of a future El Nino event, prudent management and observation will require
      consideration of the background oceanographic conditions, the type of event, and
      both the magnitude and duration of the event when assessing the potential
      physical and biological impacts on the northern California Current. 

PMID- 26220499
TI  - Differential effects of isomers of clomiphene citrate on reproductive tissues in
      male mice.
AB  - OBJECTIVES: To determine, in a chronic dosing study, the oral toxicity potential
      of the test substances, enclomiphene citrate (ENC) and zuclomiphene citrate
      (ZUC), when administered to male mice by oral gavage. MATERIALS AND METHODS: Mice
      were divided into five treatment groups. Group I, placebo; Group II, 40 mg/kg
      body weight/day ENC; Group III, 4 mg/kg/day ENC; Group IV, 40 mg/kg/day ZUC;
      Group V, 4 mg/kg/day ZUC. Serum samples and tissues were obtained from each mouse
      for analysis and body weights were measured. RESULTS: In this chronic dosing
      study in mice, profound effects on Leydig cells, epididymis, seminal vesicles,
      and kidneys were seen, as well as effects on serum testosterone, follicle
      stimulating hormone and luteinising hormone levels that were associated with ZUC
      treatment only. Treatment with the isolated enclomiphene isomer had positive
      effects on testosterone production and no effects on testicular histology.
      CONCLUSIONS: The present study suggests that an unopposed high dose of
      zuclomiphene can have pernicious effects on male mammalian reproductive organs.
      The deleterious effects seen when administering ZUC in male mice, justifies the
      case for a monoisomeric preparation and the development of ENC for clinical use
      in human males to increase serum levels of testosterone and maintain sperm
      counts.

PMID- 26220500
TI  - [Recovery of acute otitis media pathogens by anaerobic culture].

PMID- 26220501
TI  - [Epidemiological update of hydatid disease in hospitals in the public health
      system of Extremadura (2003-2012)].
AB  - INTRODUCTION: Echinococcosis is a zoonotic infection with a worldwide
      distribution, and is still an important health problem in many areas of the
      world, including the Mediterranean basin. At present the epidemiological
      situation is unclear in certain regions of Spain. The aim of this study was to
      update the epidemiological situation in Extremadura through an analysis of
      hospitalised patients in the public health system diagnosed with hydatid disease.
      METHODS: A longitudinal retrospective study was conducted between 2003 and 2012
      on hospitalised patients with a diagnosis of hydatidosis (ICD 122.0-122.9) in
      hospitals of the public health service of Extremadura. RESULTS: During the period
      of study, 876 patients were diagnosed with hydatid disease. Of these 536 (61%) of
      cases were male, with a mean age of 65.53+/-17.8 years. More importantly, 19
      (2.2%) of patients were 19 years old, with 17 cases between 2003-2007 versus 2
      cases between 2008-2012 (OR=7.83; 95%CI: 1.79-34.11; P=.001). A total of 141
      (16.0%) were younger than 45 years. The primary diagnosis was most frequently
      reported in the younger population <45 years, whereas the secondary diagnosis was
      usually found in the elderly population >70 years (P<.05). The incidence rate of
      hydatid disease obtained from Hospital Discharge Records (HDRs) was significantly
      higher compared to the incidence that was declared in the Notifiable Disease
      System of Extremadura (8.02 cases per 10(5) person-years vs. 1.88 cases per 10(5)
      person-years [P<.05]). CONCLUSION: In Extremadura hydatid disease is still
      frequent. With a clear decrease in the number of paediatric cases. The number of
      cases obtained from HDRs regarding Notification System Diseases Extremadura
      suggests the need for modifications to improve surveillance and control of
      hydatid disease.

PMID- 26220503
TI  - The Value of Rotational Venography Versus Anterior-Posterior Venography in 100
      Consecutive IVC Filter Retrievals.
AB  - PURPOSE: Accurately detecting inferior vena cava (IVC) filter complications is
      important for safe and successful retrieval as tip-embedded filters require
      removal with non-standard techniques. Venography prior to IVC filter retrieval
      has traditionally used a single anterior-posterior (AP) projection. This study
      compares the utility of rotational venography to AP venography prior to IVC
      filter removal. MATERIALS AND METHODS: The rotational venograms from 100
      consecutive IVC filter retrievals over a 35-month period were evaluated
      retrospectively. The AP view of the rotational venogram was examined separately
      from the full series by a radiologist blinded to alternative imaging and
      operative findings. The venograms were evaluated for tip embedding, filter
      fracture, filter thrombus, and IVC thrombus. Statistical analysis was performed.
      RESULTS: Using operative findings and peri-procedural imaging as the reference
      standard, tip embedding occurred in 59 of the 100 filters (59%). AP venography
      was used to correctly identify 31 tip-embedded filters (53% sensitivity) with two
      false positives (95% specificity) for an accuracy of 70%. Rotational venography
      was used to correctly identify 58 tip-embedded filters (98% sensitivity) with one
      false positive (98% specificity) for an accuracy of 98%. A significant difference
      was found in the sensitivities of the two diagnostic approaches (P < .01). Other
      findings of thrombus and filter fracture were not significantly different between
      the two groups. CONCLUSION: Rotational venograms allow for more accurate
      detection of tip-embedded IVC filters compared to AP views alone. As this
      determines the approach taken, rotational venograms are helpful if obtained prior
      to IVC filter retrieval.

PMID- 26220504
TI  - The Management of Cephalic Arch Stenosis in Arteriovenous Fistulas for
      Hemodialysis: A Systematic Review.
AB  - AIM: To conduct a systematic review of management of current cephalic arch
      stenosis (CAS) and associated outcomes in the context of dysfunctional
      hemodialysis access. MATERIALS AND METHODS: PubMed, Web of Science, and Cochrane
      Library were searched to retrieve literature on the management of CAS. Studies
      had to focus on management of access stenosis solely in the cephalic arch. Case
      reports and literature reviews were excluded. Studies were categorized by
      intervention, and primary and secondary patency data were compiled. Studies were
      aggregated, and meta-analyses were performed where possible. RESULTS: Nine papers
      satisfied the aforementioned criteria: five were retrospective studies and four
      were prospective studies. CAS management strategies have included percutaneous
      transluminal balloon angioplasty (PTA), peripheral cutting balloons, surgical
      cephalic vein transpositions, bare stents, and stent grafts. Reporting strategies
      varied between studies. Meta-analyses showed that results were variable even
      within studies using the same modality, particularly for PTA. CONCLUSION: No
      singular, definitive management strategy exists for CAS. Current studies are
      limited by being primarily single-center retrospective trials featuring
      heterogenous patient populations, interventions, and endpoints. Priorities for
      future studies should include larger randomized trials, more uniform management
      strategies and endpoints, and a longer duration of follow-up.

PMID- 26220505
TI  - Effectiveness of a Brief, Basic Evidence-Based Practice Course for Clinical
      Nurses.
AB  - BACKGROUND: Barriers to the implementation of evidence-based practice (EBP) by
      nursing professionals include a lack of knowledge, inadequate skills in searching
      for and appraising evidence, and consulting research articles. However, few
      studies have addressed the effectiveness of educational interventions to improve
      their competence. AIMS: To evaluate the effectiveness of a brief basic online and
      face-to-face educational intervention to promote EBP attitudes, knowledge and
      skills, and practice in clinical care nurses. METHODS: This study was quasi
      experimental, pretest-posttest design with a comparison group. The sample
      included registered nurses enrolled in the free continuing education courses
      offered in 2013 by the Nursing Council of Jaen (Spain). The study included 109
      participants (54 in the intervention group and 55 in the comparison group). The
      intervention was a brief, basic EBP course with online and face-to-face learning.
      The comparison group received an educational intervention with different content.
      The evidence-based practice questionnaire (EBPQ) was used to evaluate EBP
      attitude, knowledge and skills, and practice before the intervention, and at 21
      and 60 days following the intervention. Two-way mixed analysis of variance was
      conducted. RESULTS: There was a significant difference between intervention and
      comparison groups in the knowledge and skills dimension. The difference between
      groups was not significant in the EBP practice dimension. Both groups had high
      scores in the attitude dimension that did not change after the intervention.
      LINKING EVIDENCE TO ACTION: A brief basic educational intervention on EBP with
      online and face-to-face learning can produce improvements in the knowledge and
      skills of clinical nurses.

PMID- 26220502
TI  - Epigenetic regulation of the intestinal epithelium.
AB  - The intestinal epithelium is an ideal model system for the study of normal and
      pathological differentiation processes. The mammalian intestinal epithelium is a
      single cell layer comprising proliferative crypts and differentiated villi. The
      crypts contain both proliferating and quiescent stem cell populations that self
      renew and produce all the differentiated cell types, which are replaced every 3-5
      days. The genetics of intestinal development, homeostasis, and disease are well
      defined, but less is known about the contribution of epigenetics in modulating
      these processes. Epigenetics refers to heritable phenotypic traits, including
      gene expression, which are independent of mutations in the DNA sequence. We have
      known for several decades that human colorectal cancers contain hypomethylated
      DNA, but the causes and consequences of this phenomenon are not fully understood.
      In contrast, tumor suppressor gene promoters are often hypermethylated in
      colorectal cancer, resulting in decreased expression of the associated gene. In
      this review, we describe the role that epigenetics plays in intestinal
      homeostasis and disease, with an emphasis on results from mouse models. We
      highlight the importance of producing and analyzing next-generation sequencing
      data detailing the epigenome from intestinal stem cell to differentiated
      intestinal villus cell. 

PMID- 26220506
TI  - Retropubic or transobturator mid-urethral slings for intrinsic sphincter
      deficiency-related stress urinary incontinence in women: a systematic review and
      meta-analysis.
AB  - INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence is a common problem
      affecting 12-46% of women. A cohort of women have a more severe form of stress
      urinary incontinence usually due to intrinsic urethral sphincter deficiency that
      has traditionally resulted in lower success rates with standard treatment
      modalities. We aim to address the question of whether transobturator sling
      insertion is more effective than retropubic sling insertion in the treatment of
      intrinsic sphincter deficiency-related stress urinary incontinence in women.
      METHODS: We searched MEDLINE, CINAHL, CENTRAL, journals, and major conferences
      (up to 30 June 2014). All randomised controlled trials in women with stress
      urinary incontinence or mixed urinary incontinence with associated intrinsic
      sphincter deficiency who underwent a retropubic or transobturator mid-urethral
      sling operation were included in this meta-analysis. The Cochrane risk of bias
      tool and the GRADE system were used to assess the quality of evidence. RESULTS:
      Fifty-five randomised controlled trials compared transobturator and retropubic
      mid-urethral slings. Twelve trials included women with intrinsic sphincter
      deficiency, but only 8 trials (399 women) reported data specifically for this
      cohort. There was a statistically significant difference in short- and medium
      term (<=5 years) subjective cure rates, with the number of women reporting a cure
      in the transobturator group at 150 out of 199 and the retropubic group at 171 out
      of 200. This gives a 12% relative risk reduction in achieving cure with the
      transobturator route (RR 0.88, 95% CI 0.80 to 0.96, I(2) = 0%, moderate quality
      evidence [GRADE]). Objective cure was reported by five trials of 324 women and
      showed no statistically significant difference between the two groups, with a
      rate of 110 out of 159 in the transobturator group and 126 out of 165 in the
      retropubic group (RR 0.90, 95% CI 0.79 to 1.03). Post-operative voiding
      dysfunction and de novo urgency or urgency urinary incontinence in the two
      treatment groups showed no significant difference. The need to undergo repeat
      incontinence surgery in the long term (>=5 years) was higher with the
      transobturator route (RR 14.4, 95% CI 1.95 to 106, 147 women). CONCLUSIONS: Mid
      urethral slings are effective in treating women with intrinsic sphincter
      deficiency-associated stress urinary incontinence. The retropubic route resulted
      in higher subjective cure rates compared with transobturator routes. Both routes
      improved the overall quality of life.

PMID- 26220509
TI  - Retrospective evaluation of blood culture isolates and sepsis survival rate in
      foals in the Czech Republic: 50 cases (2011-2013).
AB  - OBJECTIVE: To identify the specific pathogens causing sepsis in hospitalized
      foals in the Czech Republic and identify important factors associated with their
      survival. DESIGN: A retrospective study from 2011 to 2013. SETTING: University
      veterinary teaching hospital. ANIMALS: Fifty compromised foals. INTERVENTIONS:
      None. MEASUREMENT AND MAIN RESULTS: Blood was aseptically collected for bacterial
      culture from compromised foals. The foals were classified as septic according to
      a positive blood culture result or sepsis score >=11. Blood cultures were
      positive in 44% of the foals. In these positive cultures, 27.3% had only Gram
      positive (G+) bacteria and 54.5% had only Gram-negative (G-) bacteria. A mixed
      bacterial population was presented in 18.2% of the positive cultures. Thirty-six
      foals were classified as septic on the basis of positive blood culture or a
      sepsis score >=11. In the group of foals that did not survive, there were
      significantly more foals with low levels of immunoglobulin G (IgG) than foals
      with normal levels of IgG (P < 0.0001). We also found a significant difference in
      the proportion of foals with low levels of IgG and positive blood cultures when
      compared to negative blood cultures. Twenty-six of the 50 foals were discharged
      from the hospital. Survival was significantly lower in foals with a diagnosis of
      sepsis than in foals without sepsis. There was no statistically significant
      difference between foals that died as a result of infection caused by G- or G+
      pathogens. There was no difference in the proportion of survivors that did or did
      not receive antimicrobials prior to admission. CONCLUSIONS: In our study, we
      confirmed the increasing trend for G+ bacteria in blood cultures but G- still
      predominate. The percentage of nonsurviving septic foals was high.

PMID- 26220508
TI  - Manganese-Induced Parkinsonism Is Not Idiopathic Parkinson's Disease:
      Environmental and Genetic Evidence.
AB  - Movement abnormalities caused by chronic manganese (Mn) intoxication clinically
      resemble but are not identical to those in idiopathic Parkinson's disease. In
      fact, the most successful parkinsonian drug treatment, the dopamine precursor
      levodopa, is ineffective in alleviating Mn-induced motor symptoms, implying that
      parkinsonism in Mn-exposed individuals may not be linked to midbrain dopaminergic
      neuron cell loss. Over the last decade, supporting evidence from human and
      nonhuman primates has emerged that Mn-induced parkinsonism partially results from
      damage to basal ganglia nuclei of the striatal "direct pathway" (ie, the
      caudate/putamen, internal globus pallidus, and substantia nigra pars reticulata)
      and a marked inhibition of striatal dopamine release in the absence of
      nigrostriatal dopamine terminal degeneration. Recent neuroimaging studies have
      revealed similar findings in a particular group of young drug users intravenously
      injecting the Mn-containing psychostimulant ephedron and in individuals with
      inherited mutations of the Mn transporter gene SLC30A10. This review will provide
      a detailed discussion about the aforementioned studies, followed by a comparison
      with their rodent analogs and idiopathic parkinsonism. Together, these findings
      in combination with a limited knowledge about the underlying neuropathology of Mn
      induced parkinsonism strongly support the need for a more complete understanding
      of the neurotoxic effects of Mn on basal ganglia function to uncover the
      appropriate cellular and molecular therapeutic targets for this disorder. 

PMID- 26220510
TI  - Monitoring of allograft vasculopathy by intravascular ultrasound one month and
      one year after heart transplantation: A single center study.
AB  - AIMS: The aim of this trial was to use intravascular ultrasound (IVUS) to
      determine whether cardiac allograft vasculopathy (CAV) starts progressing during
      the first year after heart transplantation (HTx). METHODS: We retrospectively
      analyzed 51 patients (11 women) who received heart transplants in our center
      between January 2010 and September 2013 and underwent coronary angiography as
      well as IVUS examination one month and one year after HTx. Patients with proven
      calcification and fibrotic plates in the IVUS examination one month after HTx
      constituted a group with defined donor-transmitted atherosclerosis (DTA). In
      patients without DTA, measurements of maximal intimal thickening (MIT) were made
      in two predetermined locations. RESULTS: Eight of the 51 patients had DTA, while
      43 did not. These were divided based on maximal intimal thickness (MIT) into a
      group with MIT < 0.5 mm (27) and MIT >= 0.5 mm (16). No patient with MIT < 0.5 mm
      developed allograft vasculopathy within one year after HTx. CAV developed in
      three patients (P = 0.045) out of the 16 patients with MIT >= 0.5. In patients
      with DTA, a statistically significant deterioration in percent area stenosis
      (PAS) occurred in both artery sections (P = 0.01). CONCLUSION: Our trial showed
      that CAV progresses during the first year after HTx significantly more frequently
      in patients with DTA and MIT >= 0.5 mm. It is essential in these patients to
      implement an IVUS control examination one year after transplantation. The results
      can lead to a change in treatment strategy to prevent further progress of the
      disease.

PMID- 26220511
TI  - Neuromodulation Technologies and the Regulation of Forms of Life: Exploring,
      Treating, Enhancing.
AB  - Deep brain stimulation (DBS) is one of the most innovative treatments for a range
      of neurological and psychiatric conditions. As the practice spreads worldwide,
      this invasive neurosurgical technology has become the subject of major social,
      scientific, and ethical concerns about its regulation. In this article, I
      describe its implementation in a French neuroscience ward and the different forms
      of practice that structure and promote the development and circulation of this
      neuromodulation technology. I explore how alternative experimental uses of DBS
      and deviations from its original therapeutic objectives both interfere with and
      promote its dissemination. At first, it appeared that neuroscientists could use
      DBS as a powerful tool to create reproducible experimental human models of
      emotional or behavioral symptoms so as to explore the functions of the human
      brain in vivo. In parallel, implanted patients influenced the care program by
      viewing DBS as a potential technology of self-enhancement for a wide range of
      personal situations. These alternative uses of DBS have challenged its modes of
      regulation and standardization and have raised new medical, scientific, and moral
      controversies. These concern not only ethical and methodological norms of medical
      and scientific practices but also the anthropological tensions raised by the
      forms of life that are emerging from neuroscience and experimental practices. 

PMID- 26220513
TI  - Characterisation of the Equine adenovirus 2 genome.
AB  - Equine adenovirus 2 (EAdV-2) is one of two serotypes of adenoviruses known to
      infect equines. Initial studies did not associate EAdV-2 infections with any
      specific clinical syndromes, although more recent evidence suggests that EAdV-2
      may be associated with clinical and subclinical gastrointestinal infections of
      foals and adults respectively. In contrast, Equine adenovirus 1 is well
      recognised as a pathogen associated with upper respiratory tract infections of
      horses. In this study the complete genome sequence of EAdV-2 is reported. As
      expected, genes common to the adenoviruses were identified. Phylogenetic
      reconstructions using selected EAdV-2 genes confirmed the classification of this
      virus within the Mastadenovirus genus, and supported the hypothesis that EAdV-2
      and EAdV-1 have evolved from separate lineages within the adenoviruses. One
      spliced open reading frame was identified that encoded for a polypeptide with
      high similarity to the pIX and E1b_55K adenovirus homologues and was designated
      pIX_E1b_55K. In addition to this fused version of E1b_55K, a separate E1b_55K
      encoding gene was also identified. These polypeptides do not appear to have
      evolved from a gene duplication event as the fused and unfused E1b_55K were most
      similar to E1b_55K homologues from the Atadenovirus and Mastadenovirus genera
      respectively. The results of this study suggest that EAdV-2 has an unusual
      evolutionary history that warrants further investigation. 

PMID- 26220514
TI  - Vaccination schedules in small ruminant farms.
AB  - Development and implementation of health management plans is the cornerstone of
      profitable farms; prevention of microbial diseases by means of vaccination is an
      integral part of such a plan. In every production type and management system in
      small ruminants, microbial diseases have a major significance, hence their proper
      control must be based in good health management practices, including use of
      effective and safe vaccines. Development of various types of vaccines is evolving
      very quickly in recent years and the improvement of new type of vaccines offers
      prospects. The article reviews and discusses vaccination programs and latest
      advances in development of vaccines against diseases that cause major economic
      losses in small ruminants. Specifically, vaccination schedules for the following
      diseases are reviewed: bacterial abortion (abortion associated with Brucella
      melitensis, Campylobacter spp., Chlamydophila abortus, Coxiella burnetii,
      Salmonella abortus ovis or Salmonella brandenburg), caseous lymphadenitis,
      clostridial diseases, colibacillosis, contagious echtyma, epididymitis caused by
      Brucella ovis, footrot, mammary diseases (contagious agalactia, mastitis),
      paratuberculosis and respiratory diseases (respiratory disease caused by
      Mannheimia haemolytica or other Pasteurellaceae). 

PMID- 26220512
TI  - Occurrence of oral Candida colonization and its risk factors among patients with
      malignancies in China.
AB  - OBJECTIVES: Oral colonization of Candida could lead to later development of
      oropharyngeal candidiasis or candidemia among the immunocompromised patients.
      This study aims to describe the occurrence and risk factors of oral Candida
      colonization in patients with malignancies. MATERIALS AND METHODS: From October
      2012 to March 2013, 78 patients with pulmonary cancer (group I), 101 patients
      with gastrointestinal tract tumor (group II), 79 patients with hematopoietic
      system malignant tumor (group III), and 101 healthy controls were consecutively
      recruited in a hospital in Beijing, China. The oral rinse samples were taken and
      Candida species were identified; the enzymes activities were tested. RESULTS: In
      total, 110 and 27 Candida strains were isolated from 91 patients and 26 controls,
      respectively. The oral colonization rate with Candida albicans in group III (12.7
      %) was significant lower than that in group I (30.8 %), group II (33.7 %), and
      control group (25.7 %). The oral colonization rates with non-albicans Candida
      species in group I, group II, and group III were 15.4, 10.9, and 12.7 %,
      respectively, while only one non-albicans Candida strain was identified in
      control group. The non-albicans Candida species exhibited a lower virulence than
      C. albicans. Age was an independent risk factor for Candida colonization in
      patients with pulmonary cancer and digestive tract malignant tumor, "Teeth brush
      <1 time/day" was an independent risk factor for Candida colonization in patients
      with hematopoietic system tumor. CONCLUSIONS: The differences of risk factors for
      oral Candida colonization in patients with different cancers require different
      strategies for the prevention and control of Candida infection. CLINICAL
      RELEVANCE: Old aged patients with pulmonary cancer and digestive tract malignant
      tumor are high-risk population for Candida colonization. Increasing frequency of
      teeth brush might be helpful for preventing Candida colonization.

PMID- 26220515
TI  - Discrimination of "grazing milk" using milk fatty acid profile in the grassland
      dairy area in Hokkaido.
AB  - Milk produced by the grazing system, referred to as "grazing milk" contains many
      components required for human health. The milk fatty acid (FA) profile is
      strongly associated with the diet on the farms. In the present study, based on
      the FA profile of farmer's bulk milk, we determined how to discriminate between
      milk produced on grazing and on a confinement system. A field survey was
      conducted four times (grazing and confinement season) in the Konsen (29 farms)
      and Okhotsk (25 farms) area in Hokkaido. Farmer's bulk milk samples and details
      of feeding management were collected and the FA profile of milk was measured.
      Milk produced during the grazing season contained less C16:0 and cis-9 C16:0, and
      more C18:0, cis-9 C18:1, trans-11 C18:1, cis-9,12 C18:2, cis-9,trans-11 C18:2 and
      cis-9,12,15 C18:3 than milk produced during the confinement season.
      Discrimination analysis using 16 FA revealed that almost all milk samples were
      discriminated correctly (confinement season: 90% correct and 10% borderline,
      grazing season: 88% correct, 9% borderline and 3% incorrect). For farmers that
      were categorized incorrectly and were considered borderline in the grazing
      season, the dependency on pasture was low compared with that for farmers
      correctly discriminated. Therefore, to claim "grazing milk", a high dependency on
      pasture is required for grazing dairy farmers. 

PMID- 26220516
TI  - Prenatal ethanol exposure induces the osteoarthritis-like phenotype in female
      adult offspring rats with a post-weaning high-fat diet and its intrauterine
      programming mechanisms of cholesterol metabolism.
AB  - Osteoarthritis (OA) development is associated with hypercholesterolemia in
      adults. Our previous study demonstrated that offspring with intrauterine growth
      retardation (IUGR) due to prenatal ethanol exposure (PEE) had a high risk of
      developing hypercholesterolemia and metabolic syndrome when fed a post-weaning
      high-fat diet (HFD). In this study, we examined the changes in articular
      chondrocytes of IUGR offspring induced by PEE and explored its intrauterine
      programming mechanisms related to cholesterol metabolism. Using the PEE/IUGR
      model, serum and tibias from female fetuses and adult female offspring fed a post
      weaning HFD were collected and examined for cholesterol metabolism and histology.
      The results showed that PEE adult offspring manifested significant catch-up
      growth. Their serum total cholesterol (TCH) and low-density lipoprotein
      cholesterol increased and high-density lipoprotein-cholesterol decreased; the
      osteoarthritis-like phenotype and an increased TCH content were observed in
      articular cartilage; and the expression of insulin-like growth factor1 (IGF1) and
      cholesterol efflux pathway, including ATP-binding-cassette transporter A1 and
      liver X receptor, was reduced. The expression of IGF1 and cholesterol efflux
      pathway was also lower in the PEE fetuses. This study showed PEE could induce an
      enhanced susceptibility to HFD-induced OA in adult female IUGR offspring. The
      underlying mechanism related to cholesterol accumulation in cartilage mediated by
      intrauterine programming. 

PMID- 26220517
TI  - Comparison of human Nrf2 antibodies: A tale of two proteins.
AB  - The Nrf2 transcription factor is a master regulator of the cellular defense
      against oxidative and electrophilic stress. An increase in Nrf2 protein levels
      and an accumulation of Nrf2 in the nucleus are key parts of the Nrf2 activation
      mechanism. The western blot technique remains the most widely used method to
      assess these changes. A well-characterized, specific antibody that is
      commercially available would greatly enhance these studies in the field. Here, an
      apparently highly specific Nrf2 monoclonal antibody, EP1808Y from Abcam, is
      compared with the most widely used Nrf2 antibodies, H-300 and C-20, both from
      Santa Cruz Biotechnology, in a panel of human cell lines. In addition to
      detecting Nrf2, EP1808Y avidly detects another protein present in two of the
      three cell lines tested. This protein can be mistaken for Nrf2 as it co-migrates
      with verified Nrf2 on two different polyacrylamide gel types. However, unlike
      Nrf2, its levels and cytoplasmic localization are unaffected by treatment with
      Nrf2 activators. The possibility that this band corresponds to a form of Nrf2 was
      excluded by siRNA and immunodepletion experiments. Finally, the monoclonal
      antibody D1Z9C from Cell Signaling was found to detect Nrf2 with the highest
      specificity of these four antibodies. 

PMID- 26220518
TI  - Kinetics of pesticide degradation by human fresh frozen plasma (FFP) in vitro.
AB  - There is an ongoing debate about the benefit of fresh frozen plasma (FFP)
      infusion in organophosphorus (OP) pesticide-poisoned patients. This prompted us
      to investigate the kinetics of OP pesticide degradation by FFP with an enzymatic
      assay in vitro. Degradation was rapid with shortest half-lives of 19.5s for
      chlorpyrifos-oxon, 6.3min for paraoxon-ethyl and 17.9min for dichlorvos.
      Heptenophos (78.0min), mevinphos (101.8min), profenofos (162.3min) and malaoxon
      (179.7min) showed half-lives of up to 3h. Substantial longer degradation half
      lives of 69.7-80.8h were determined with chlorfenvinphos and bromfenvinphos.
      Methamidophos and omethoate showed no degradation by FFP indicated by half-lives
      similar to spontaneous hydrolysis. In conclusion, degradation by FFP depends on
      the particular OP pesticide and the used FFP batch. 

PMID- 26220519
TI  - Design and synthesis of new non nucleoside inhibitors of DNMT3A.
AB  - DNA methylation, an epigenetic modification regulating gene expression, is a
      promising target in cancer. In an effort to identify new non nucleosidic
      inhibitors of DNA methyltransferases, the enzymes responsible for DNA
      methylation, we carried out a high-throughput screening of 66,000 chemical
      compounds based on an enzymatic assay against catalytic DNMT3A. A family of
      propiophenone derivatives was identified. After chemical optimization and
      structure activity relationship studies, a new inhibitor (33) was obtained with
      an EC50 of 2.1 MUM against DNMT3A. The mechanism of inhibition of the compound
      was investigated as it forms a reactive Michael acceptor group in situ. Thereby,
      the Michael acceptor 20 was identified. This compound was further characterized
      for its biological activity in cancer cells.

PMID- 26220520
TI  - Factors that influence T box riboswitch efficacy and tRNA affinity.
AB  - The T box riboswitch is an intriguing potential target for antibacterial drug
      discovery. Found primarily in Gram-positive bacteria, the riboswitch regulates
      gene expression by selectively responding to uncharged tRNA to control
      transcription readthrough. Polyamines and molecular crowding are known to
      specifically affect RNA function, but their effect on T box riboswitch efficacy
      and tRNA affinity have not been fully characterized. A fluorescence-monitored in
      vitro transcription assay was developed to readily quantify these molecular
      interactions and to provide a moderate-throughput functional assay for a
      comprehensive drug discovery screening cascade. The polyamine spermidine
      specifically enhanced T box riboswitch readthrough efficacy with an EC50 = 0.58
      mM independent of tRNA binding. Molecular crowding, simulated by the addition of
      polyethylene glycol, had no effect on tRNA affinity for the riboswitch, but did
      reduce the efficacy of tRNA-induced readthrough. These results indicate that the
      T box riboswitch tRNA affinity and readthrough efficacy are intricately modulated
      by environmental factors.

PMID- 26220521
TI  - Physical activity is associated with lower arterial stiffness in older adults:
      results of the SAPALDIA 3 Cohort Study.
AB  - Associations of physical activity (PA) intensity with arterial stiffness in older
      adults at the population level are insufficiently studied. We examined cross
      sectional associations of self-reported PA intensities with arterial stiffness in
      elderly Caucasians of the Swiss Cohort Study on Air Pollution and Lung and Heart
      Diseases in Adults. Mixed central and peripheral arterial stiffness was measured
      oscillometrically by the cardio-ankle vascular index (CAVI) and brachial-ankle
      pulse wave velocity (baPWV). The self-reported International Physical Activity
      Questionnaire long version was administered to classify each subject's PA level.
      We used univariable and multivariable mixed linear and logistic regression models
      for analyses in 1908 persons aged 50 years and older. After adjustment for
      several confounders moderate, vigorous and total PA were inversely associated
      with CAVI (p = 0.02-0.03). BaPWV showed negative and marginally significant
      associations with vigorous and moderate PA (each p = 0.06), but not with total PA
      (p = 0.28). Increased arterial stiffness (CAVI >= 9, upper tertile) was inversely
      and significantly associated with vigorous PA [odds ratio (OR) 0.65, 95%
      confidence interval (CI) 0.48-0.88], and marginally significantly with total PA
      (OR 0.76, 95% CI 0.57-1.02) and moderate PA (OR 0.75, 95% CI 0.56-1.01). The odds
      ratio for baPWV >= 14.4 was 0.67 (95% CI 0.48-0.93) across the vigorous PA
      levels, and was non-significant across the total (OR 0.91, 95% CI 0.66-1.23) and
      moderate PA levels (OR 0.94, 95% CI 0.69-1.28). In this general Caucasian
      population of older adults higher levels especially of vigorous PA were
      associated with lower arterial stiffness. These data support the importance of PA
      for improving cardiovascular health in elderly people.

PMID- 26220522
TI  - Amyotrophic lateral sclerosis among cross-country skiers in Sweden.
AB  - A highly increased risk of amyotrophic lateral sclerosis (ALS) has been suggested
      among professional athletes. We aimed to examine whether long distance cross
      country skiers have also a higher risk of ALS and whether the increased risk was
      modified by skiing performance. We followed 212,246 cross-country skiers in the
      Swedish Vasaloppet cohort and a random selection of 508,176 general Swedes not
      participating in the Vasaloppet during 1989-2010. The associations between cross
      country skiing as well as skiing performance (i.e., type of race, finishing time
      and number of races) and the consequent risk of ALS were estimated through hazard
      ratios (HRs) derived from Cox model. During the study, 39 cases of ALS were
      ascertained among the skiers. The fastest skiers (100-150% of winner time) had
      more than fourfold risk of ALS (HR 4.31, 95% confidence interval [CI] 1.78-10.4),
      as compared to skiers that finished at >180% of winner time. Skiers who
      participated >4 races during this period had also a higher risk (HR 3.13, 95% CI
      1.37-7.17) than those participated only one race. When compared to the non
      skiers, the fastest skiers still had a higher risk (HR 2.08, 95% CI 1.12-3.84),
      as skiers who had >4 races (HR 1.88, 95% CI 1.05-3.35), but those finishing at
      >180% of winner time had a lower risk (HR 0.46, 95% CI 0.24-0.87). In conclusion,
      long distance cross-country skiing is associated with a higher risk of ALS, but
      only among the best skiers; recreational skiers appear to have a largely reduced
      risk.

PMID- 26220523
TI  - LK6/Mnk2a is a new kinase of alpha synuclein phosphorylation mediating
      neurodegeneration.
AB  - Parkinson's disease (PD) is a movement disorder due to the loss of dopaminergic
      (DA) neurons in the substantia nigra. Alpha-synuclein phosphorylation and alpha
      synuclein inclusion (Lewy body) become a main contributor, but little is known
      about their formation mechanism. Here we used protein expression profiling of PD
      to construct a model of their signalling network from drsophila to human and
      nominate major nodes that regulate PD development. We found in this network that
      LK6, a serine/threonine protein kinase, plays a key role in promoting alpha
      synuclein Ser129 phosphorylation by identification of LK6 knockout and
      overexpression. In vivo test was further confirmed that LK6 indeed enhances alpha
      synuclein phosphorylation, accelerates the death of dopaminergic neurons, reduces
      the climbing ability and shortens the the life span of drosophila. Further, MAP
      kinase-interacting kinase 2a (Mnk2a), a human homolog of LK6, also been shown to
      make alpha-synuclein phosphorylation and leads to alpha-synuclein inclusion
      formation. On the mechanism, the phosphorylation mediated by LK6 and Mnk2a is
      controlled through ERK signal pathway by phorbolmyristate acetate (PMA)
      avtivation and PD98059 inhibition. Our findings establish pivotal role of Lk6 and
      Mnk2a in unprecedented signalling networks, may lead to new therapies preventing
      alpha-synuclein inclusion formation and neurodegeneration. 

PMID- 26220524
TI  - Loss of ATM accelerates pancreatic cancer formation and epithelial-mesenchymal
      transition.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is associated with accumulation of
      particular oncogenic mutations and recent genetic sequencing studies have
      identified ataxia telangiectasia-mutated (ATM) mutations in PDAC cohorts. Here we
      report that conditional deletion of ATM in a mouse model of PDAC induces a
      greater number of proliferative precursor lesions coupled with a pronounced
      fibrotic reaction. ATM-targeted mice display altered TGFbeta-superfamily
      signalling and enhanced epithelial-to-mesenchymal transition (EMT) coupled with
      shortened survival. Notably, our mouse model recapitulates many features of more
      aggressive human PDAC subtypes. Particularly, we report that low expression of
      ATM predicts EMT, a gene signature specific for Bmp4 signalling and poor
      prognosis in human PDAC. Our data suggest an intimate link between ATM expression
      and pancreatic cancer progression in mice and men. 

PMID- 26220525
TI  - An in vivo genetic reversion highlights the crucial role of Myb-Like, SWIRM, and
      MPN domains 1 (MYSM1) in human hematopoiesis and lymphocyte differentiation.
AB  - BACKGROUND: Myb-Like, SWIRM, and MPN domains 1 (MYSM1) is a metalloprotease that
      deubiquitinates the K119-monoubiquitinated form of histone 2A (H2A), a chromatin
      marker associated with gene transcription silencing. Likewise, it has been
      reported that murine Mysm1 participates in transcription derepression of genes,
      among which are transcription factors involved in hematopoietic stem cell
      homeostasis, hematopoiesis, and lymphocyte differentiation. However, whether
      MYSM1 has a similar function in human subjects remains unclear. Here we describe
      a patient presenting with a complete lack of B lymphocytes, T-cell lymphopenia,
      defective hematopoiesis, and developmental abnormalities. OBJECTIVES: We sought
      to characterize the underlying genetic cause of this syndrome. METHODS: We
      performed genome-wide homozygosity mapping, followed by whole-exome sequencing.
      RESULTS: Genetic analysis revealed that this novel disorder is caused by a
      homozygous MYSM1 missense mutation affecting the catalytic site within the
      deubiquitinase JAB1/MPN/Mov34 (JAMM)/MPN domain. Remarkably, during the course of
      our study, the patient recovered a normal immunohematologic phenotype. Genetic
      analysis indicated that this improvement originated from a spontaneous genetic
      reversion of the MYSM1 mutation in a hematopoietic stem cell. CONCLUSIONS: We
      here define a novel human immunodeficiency and provide evidence that MYSM1 is
      essential for proper immunohematopoietic development in human subjects. In
      addition, we describe one of the few examples of spontaneous in vivo genetic cure
      of a human immunodeficiency.

PMID- 26220526
TI  - Use of asthma medication during pregnancy and risk of specific congenital
      anomalies: A European case-malformed control study.
AB  - BACKGROUND: Pregnant women with asthma need to take medication during pregnancy.
      OBJECTIVE: We sought to identify whether there is an increased risk of specific
      congenital anomalies after exposure to antiasthma medication in the first
      trimester of pregnancy. METHODS: We performed a population-based case-malformed
      control study testing signals identified in a literature review. Odds ratios
      (ORs) of exposure to the main groups of asthma medication were calculated for
      each of the 10 signal anomalies compared with registrations with nonchromosomal,
      nonsignal anomalies as control registrations. In addition, exploratory analyses
      were done for each nonsignal anomaly. The data set included 76,249 registrations
      of congenital anomalies from 13 EUROmediCAT registries. RESULTS: Cleft palate
      (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had
      significantly increased odds of exposure to first-trimester use of inhaled beta2
      agonists compared with nonchromosomal control registrations. Odds of exposure to
      salbutamol were similar. Nonsignificant ORs of exposure to inhaled beta2-agonists
      were found for spina bifida, cleft lip, anal atresia, severe congenital heart
      defects in general, or tetralogy of Fallot. None of the 4 literature signals of
      exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal
      atresia, and hypospadias). Exploratory analyses found an association between
      renal dysplasia and exposure to the combination of long-acting beta2-agonists and
      inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85). CONCLUSIONS: The study
      confirmed increased odds of first-trimester exposure to inhaled beta2-agonists
      for cleft palate and gastroschisis and found a potential new signal for renal
      dysplasia associated with combined long-acting beta2-agonists and inhaled
      corticosteroids. Use of inhaled corticosteroids during the first trimester of
      pregnancy seems to be safe in relation to the risk for a range of specific major
      congenital anomalies.

PMID- 26220527
TI  - "Inflammatory skin march": IL-1-mediated skin inflammation, atopic dermatitis,
      and psoriasis to cardiovascular events.

PMID- 26220528
TI  - Inhibition of eosinophil apoptosis by asthma-relevant cytokines from platelets.

PMID- 26220529
TI  - Predictive value of nonspecific bronchial responsiveness in occupational asthma.
AB  - BACKGROUND: The diagnosis of occupational asthma (OA) can be challenging and
      needs a stepwise approach. However, the predictive value of the methacholine
      challenge has never been addressed specifically in this context. OBJECTIVE: We
      sought to evaluate the sensitivity, specificity, and positive and negative
      predictive values of the methacholine challenge in OA. METHODS: A Canadian
      database was used to review 1012 cases of workers referred for a suspicion of OA
      between 1983 and 2011 and having had a specific inhalation challenge. We
      calculated the sensitivity, specificity, and positive and negative predictive
      values of methacholine challenges at baseline of the specific inhalation
      challenge, at the workplace, and outside work. RESULTS: At baseline, the
      methacholine challenge showed an overall sensitivity of 80.2% and a specificity
      of 47.1%, with positive and negative predictive values of 36.5% and 86.3%,
      respectively. Among the 430 subjects who were still working, the baseline
      measures displayed a sensitivity of 95.4%, a specificity of 40.1%, and positive
      and negative predictive values of 41.1% and 95.2%, respectively. Among the 582
      subjects tested outside work, the baseline measures demonstrated a sensitivity
      and specificity of 66.7% and 52%, respectively, and positive and negative
      predictive values of 31.9% and 82.2%, respectively. When considering all subjects
      tested by a methacholine challenge at least once while at work (479), the
      sensitivity, specificity, and positive and negative predictive values were 98.1%,
      39.1%, and 44.0% and 97.7%, respectively. CONCLUSION: A negative methacholine
      challenge in a patient still exposed to the causative agent at work makes the
      diagnosis of OA very unlikely.

PMID- 26220530
TI  - Allergic sensitization is age-dependently associated with rhinitis, but less so
      with asthma.
AB  - BACKGROUND: Epidemiologic data describing the association between allergic
      sensitization and asthma and allergic rhinitis in adults are scarce. OBJECTIVE:
      To determine the prevalence and impact of specific sensitization to airborne
      allergens on asthma and allergic rhinitis among adults in relation to age.
      METHODS: A random population sample (age 21-86 years) was examined with
      structured interview and analysis of specific IgE to 9 common airborne allergens.
      Of those invited, 692 (68%) subjects participated in blood sampling. IgE level of
      0.35 U/mL or more to the specific allergen was defined as a positive test result.
      RESULTS: Allergic sensitization decreased with increasing age, both in the
      population sample and among subjects with asthma and allergic rhinitis. In a
      multivariate model, sensitization to animal was significantly positively
      associated with asthma (odds ratio [OR], 4.80; 95% CI, 2.68-8.60), whereas
      sensitization to both animal (OR, 3.90; 95% CI, 2.31-6.58) and pollen (OR, 4.25;
      95% CI, 2.55-7.06) was significantly associated with allergic rhinitis. The
      association between allergic sensitization and rhinitis was consistently
      strongest among the youngest age group, whereas this pattern was not found for
      asthma. The prevalence of allergic sensitization among patients with asthma
      decreased by increasing age of asthma onset, 86% with asthma onset at age 6 y or
      less, 56% at age 7 to 19 years, and 26% with asthma onset at age 20 years or
      more. CONCLUSIONS: Sensitization to animal was associated with asthma across all
      age groups; allergic rhinitis was associated with sensitization to both pollen
      and animal and consistently stronger among younger than among older adults. Early
      onset of asthma was associated with allergic sensitization among adults with
      asthma.

PMID- 26220532
TI  - Reply: To PMID 25579484.

PMID- 26220531
TI  - The airway microbiome in patients with severe asthma: Associations with disease
      features and severity.
AB  - BACKGROUND: Asthma is heterogeneous, and airway dysbiosis is associated with
      clinical features in patients with mild-to-moderate asthma. Whether similar
      relationships exist among patients with severe asthma is unknown. OBJECTIVE: We
      sought to evaluate relationships between the bronchial microbiome and features of
      severe asthma. METHODS: Bronchial brushings from 40 participants in the
      Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid
      refractory Asthma (BOBCAT) study were evaluated by using 16S ribosomal RNA-based
      methods. Relationships to clinical and inflammatory features were analyzed among
      microbiome-profiled subjects. Secondarily, bacterial compositional profiles were
      compared between patients with severe asthma and previously studied healthy
      control subjects (n = 7) and patients with mild-to-moderate asthma (n = 41).
      RESULTS: In patients with severe asthma, bronchial bacterial composition was
      associated with several disease-related features, including body mass index (P <
      .05, Bray-Curtis distance-based permutational multivariate analysis of variance;
      PERMANOVA), changes in Asthma Control Questionnaire (ACQ) scores (P < .01),
      sputum total leukocyte values (P = .06), and bronchial biopsy eosinophil values
      (per square millimeter, P = .07). Bacterial communities associated with worsening
      ACQ scores and sputum total leukocyte values (predominantly Proteobacteria)
      differed markedly from those associated with body mass index
      (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ scores and
      bronchial epithelial gene expression of FK506 binding protein (FKBP5), an
      indicator of steroid responsiveness, correlated with Actinobacteria. Mostly
      negative correlations were observed between biopsy eosinophil values and
      Proteobacteria. No taxa were associated with a TH2-related epithelial gene
      expression signature, but expression of TH17-related genes was associated with
      Proteobacteria. Patients with severe asthma compared with healthy control
      subjects or patients with mild-to-moderate asthma were significantly enriched in
      Actinobacteria, although the largest differences observed involved a Klebsiella
      genus member (7.8-fold increase in patients with severe asthma, adjusted P <
      .001). CONCLUSIONS: Specific microbiota are associated with and may modulate
      inflammatory processes in patients with severe asthma and related phenotypes.
      Airway dysbiosis in patients with severe asthma appears to differ from that
      observed in those with milder asthma in the setting of inhaled corticosteroid
      use.

PMID- 26220533
TI  - Effects of formoterol or salmeterol on impulse oscillometry in patients with
      persistent asthma.
AB  - BACKGROUND: Effects of small-particle long-acting beta-agonists on the small
      airways have been poorly documented. OBJECTIVE: We used impulse oscillometry
      (IOS) to compare single and repeated dosing effects of small- and large-particle
      long-acting beta-agonists. METHODS: After a 1- to 2-week run-in period, patients
      received either 12 MUg of small-particle hydrofluoroalkane 134a-formoterol
      solution or 50 MUg of large-particle salmeterol dry powder twice daily plus
      inhaled corticosteroid for 1 to 2 weeks with a 1- to 2-week washout period in
      between. Measurements were made over 60 minutes after the first and last doses.
      RESULTS: Sixteen patients completed the study as follows: mean age, 43 years;
      FEV1, 80%; forced midexpiratory flow between 25% and 75% of forced vital capacity
      (FEF(25-75)), 48%; total airway resistance at 5 Hz, 177%; peripheral airway
      resistance as the difference between 5 and 20 Hz, 0.18 kPa.L(-1).s; Asthma
      Control Questionnaire score, 0.76; and inhaled corticosteroid dosage, 550 MUg/d.
      There were significantly greater improvements with formoterol versus salmeterol
      in all IOS outcomes and FEF25-75, but not FEV1, at 5 minutes after the first
      dose, which were not sustained over 60 minutes. After the last dose, all IOS
      outcomes, but not FEV1 or FEF(25-75), were significantly better with formoterol
      over the entire 60 minutes: mean difference at 60 minutes between formoterol and
      salmeterol in total airway resistance at 5 Hz, 7.50% (95% CI, 1.56% to 13.43%, P
      = .02); central airway resistance at 20 Hz, 5.37% (95% CI, 0.13% to 10.62%, P =
      .045); peripheral airway resistance as the difference between 5 and 20 Hz, 12.76%
      (95% CI, 1.28% to 24.24%, P = .03); reactance area under the curve, 19.46% (95%
      CI, 7.56% to 31.36%, P = .003); reactance at 5 Hz, 11.19% (95% CI, 4.62% to
      17.76%, P = .002); and resonant frequency, 9.34% (95% CI, 3.21% to 15.47%, P =
      .005). Peak expiratory flow significantly improved to a similar degree with both
      drugs. CONCLUSION: Significant improvements in IOS outcomes but not spirometry
      results occurred after chronic dosing with formoterol compared with salmeterol.
      This might reflect better deposition to the entire lung, including the small
      airways.

PMID- 26220534
TI  - Quantitative Proteomic Analyses of Molecular Mechanisms Associated with
      Cytoplasmic Incompatibility in Drosophila melanogaster Induced by Wolbachia.
AB  - To investigate the molecular mechanisms of cytoplasmic incompatibility (CI)
      induced by Wolbachia bacteria in Drosophila melanogaster, we applied an isobaric
      tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic
      assay to identify differentially expressed proteins extracted from spermathecae
      and seminal receptacles (SSR) of uninfected females mated with either 1-day-old
      Wolbachia-uninfected (1T) or infected males (1W) or 5-day-old infected males
      (5W). In total, 1317 proteins were quantified; 83 proteins were identified as
      having at least a 1.5-fold change in expression when 1W was compared with 1T.
      Differentially expressed proteins were related to metabolism, immunity, and
      reproduction. Wolbachia changed the expression of seminal fluid proteins (Sfps).
      Wolbachia may disrupt the abundance of proteins in SSR by affecting ubiquitin
      proteasome-mediated proteolysis. Knocking down two Sfp genes (CG9334 and CG2668)
      in Wolbachia-free males resulted in significantly lower embryonic hatch rates
      with a phenotype of chromatin bridges. Wolbachia-infected females may rescue the
      hatch rates. This suggests that the changed expression of some Sfps may be one of
      the mechanisms of CI induced by Wolbachia. This study provides a panel of
      candidate proteins that may be involved in the interaction between Wolbachia and
      their insect hosts and, through future functional studies, may help to elucidate
      the underlying mechanisms of Wolbachia-induced CI. 

PMID- 26220535
TI  - Bayesian hierarchical models for network meta-analysis incorporating nonignorable
      missingness.
AB  - Network meta-analysis expands the scope of a conventional pairwise meta-analysis
      to simultaneously compare multiple treatments, synthesizing both direct and
      indirect information and thus strengthening inference. Since most of trials only
      compare two treatments, a typical data set in a network meta-analysis managed as
      a trial-by-treatment matrix is extremely sparse, like an incomplete block
      structure with significant missing data. Zhang et al. proposed an arm-based
      method accounting for correlations among different treatments within the same
      trial and assuming that absent arms are missing at random. However, in randomized
      controlled trials, nonignorable missingness or missingness not at random may
      occur due to deliberate choices of treatments at the design stage. In addition,
      those undertaking a network meta-analysis may selectively choose treatments to
      include in the analysis, which may also lead to missingness not at random. In
      this paper, we extend our previous work to incorporate missingness not at random
      using selection models. The proposed method is then applied to two network meta
      analyses and evaluated through extensive simulation studies. We also provide
      comprehensive comparisons of a commonly used contrast-based method and the arm
      based method via simulations in a technical appendix under missing completely at
      random and missing at random.

PMID- 26220536
TI  - Self-modeling ordinal regression with time invariant covariates - An application
      to prostate cancer data.
AB  - In a prostate cancer study, the severity of genito-urinary (bladder) toxicity is
      assessed for patients who were given different doses of radiation. The ordinal
      responses (severity of side effects) are recorded longitudinally along with the
      cancer stage of a patient. Differences among the patients due to time-invariant
      covariates are captured by the parameters. To build up a suitable framework for
      an analysis of such data, we propose the use of self-modeling ordinal
      longitudinal model where the conditional cumulative probabilities for a category
      of an outcome have a relation with shape-invariant model. Since patients
      suffering from a common disease usually exhibit a similar pattern, it is natural
      to build up a nonlinear model that is shape invariant. The model is essentially
      semi-parametric where the population time curve is modeled with penalized
      regression spline. Monte Carlo expectation maximization technique is used to
      estimate the parameters of the model. A simulation study is also carried out to
      justify the methodology used.

PMID- 26220537
TI  - Bayesian accelerated failure time model for space-time dependency in a
      geographically augmented survival model.
AB  - In this paper, we extend the spatially explicit survival model for small area
      cancer data by allowing dependency between space and time and using accelerated
      failure time models. Spatial dependency is modeled directly in the definition of
      the survival, density, and hazard functions. The models are developed in the
      context of county level aggregated data. Two cases are considered: the first
      assumes that the spatial and temporal distributions are independent; the second
      allows for dependency between the spatial and temporal components. We apply the
      models to prostate cancer data from the Louisiana SEER cancer registry.

PMID- 26220538
TI  - Prevalence and determinants of chronic kidney disease in rural and urban
      Cameroonians: a cross-sectional study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a global public health problem that
      disproportionally affects people of African ethnicity. We assessed the prevalence
      and determinants of CKD and albuminuria in urban and rural adults Cameroonians.
      METHODS: This was a cross-sectional study of 6-month duration (February to July
      2014), conducted in the health district of Dschang (Western Region of Cameroon),
      using a multistage cluster sampling. All adults diagnosed with albuminuria (>= 30
      mg/g) and/or decreased estimated glomerular filtration rate (eGFR) (< 60
      ml/min/1.73 m(2)) were re-examined three months later. Logistic regression models
      were used to relate baseline characteristics with prevalent CKD. RESULTS: We
      included 439 participants with a mean age of 47 +/- 16.1 years; with 185 (42.1 %)
      being men and 119 (27.1 %) being urban dwellers. There was a high prevalence of
      hypertension (25.5 %), diabetes (9.8 %), smoking (9.3 %), alcohol consumption
      (59.7 %), longstanding use of herbal medicine (90.9 %) and street medications
      (87.5 %), and overweight/obesity (53.3 %) which were predominant in rural area.
      The prevalence of CKD was 13.2 % overall, 14.1 % in rural and 10.9 % in urban
      participants. Equivalents figures for CKD stages G3-G4 and albuminuria were 2.5
      %, 1.6 % and 5.0 %; and 12.1 %, 14.1 % and 6.7 % respectively. Existing
      hypertension and diabetes were associated with all outcomes. Elevated systolic
      blood pressure and the presence of hypertension and diabetes were the predictors
      of albuminuria and CKD while urban residence was associated with CKD stages G3
      G4. CONCLUSION: The prevalence of CKD and albuminuria was high in this
      population, predominantly in rural area, and driven mostly by the commonest risk
      factors.

PMID- 26220543
TI  - In silico Investigation of the PglB Active Site Reveals Transient Catalytic
      States and Octahedral Metal Ion Coordination.
AB  - The last step of the bacterial N-glycosylation pathway involves PglB, an
      oligosaccharyltransferase, which is responsible for the en bloc transfer of a
      fully assembled oligosaccharide chain to a protein possessing the extended motif
      D/E-X-N-X-S/T. Recently, this molecule had its full structure elucidated,
      enabling the description of its domains and the proposition of a catalytic
      mechanism. By employing molecular dynamics simulations, we were able to evaluate
      structural aspects of PglB, suggesting prevalent motions that may bring insights
      into the mechanism of the glycosylated peptide detachment. Additionally, we
      identified transient states at the catalytic site, in which the previously
      described carboxamide twisting mechanism was observed. Aided by quantum mechanics
      calculations for each different conformational states of the catalytic site, we
      determined the presence of an octahedral metal coordination, along with the
      presence of one water molecule at the catalytic site. 

PMID- 26220545
TI  - Missed diagnostic opportunities and English general practice: a study to
      determine their incidence, confounding and contributing factors and potential
      impact on patients through retrospective review of electronic medical records.
AB  - BACKGROUND: Patient safety research has focused largely on hospital settings
      despite the fact that in many countries, the majority of patient contacts are in
      primary care. The knowledge base about patient safety in primary care is
      developing but sparse and diagnostic error is a relatively understudied and an
      unmeasured area of patient safety. Diagnostic error rates vary according to how
      'error' is defined but one suggested hallmark is clear evidence of 'missed
      opportunity' (MDOs) makes a correct or timely diagnosis to prevent them. While
      there is no agreed definition or method of measuring MDOs, retrospective manual
      chart or patient record reviews are a 'gold standard'. This study protocol aims
      to (1) determine the incidence of MDOs in English general practice, (2) identify
      the confounding and contributing factors that lead to MDOs and (3) determine the
      (potential) impact of the detected MDOs on patients. METHODS/DESIGN: We plan to
      conduct a two-phase retrospective review of electronic health records in the
      Greater Manchester (GM) area of the UK. In the first phase, clinician reviewers
      will calibrate their performance in identifying and assessing MDOs against a gold
      standard 'primary reviewer' through the use of 'double' reviews of records. The
      findings will enable a preliminary estimate of the incidence of MDOs in general
      practice, which will be used to calculate the number of records to be reviewed in
      the second phase in order to estimate the true incidence of MDO in general
      practice. A sample of 15 general practices is required for phase 1 and up to 35
      practices for phase 2. In each practice, the sample will consist of 100 patients
      aged >=18 years on 1 April 2013 who have attended a face-to-face 'index
      consultation' between 1 April 2013 and 31 March 2015. The index consultation will
      be selected randomly from each unique patient record, occurring between 1 July
      2013 and 30 June 2014. DISCUSSION: There are no reliable estimates of safety
      problems related to diagnosis in English general practice. This study will lay
      the foundation for safety improvements in this area by providing a more reliable
      estimate of MDOs, their impact and their contributory factors.

PMID- 26220546
TI  - Molecular characterization of systemic sclerosis esophageal pathology identifies
      inflammatory and proliferative signatures.
AB  - INTRODUCTION: Esophageal involvement in patients with systemic sclerosis (SSc) is
      common, but tissue-specific pathological mechanisms are poorly understood. There
      are no animal scleroderma esophagus models and esophageal smooth muscle cells
      dedifferentiate in culture prohibiting in vitro studies. Esophageal fibrosis is
      thought to disrupt smooth muscle function and lead to esophageal dilatation, but
      autopsy studies demonstrate esophageal smooth muscle atrophy and the absence of
      fibrosis in the majority of SSc cases. Herein, we perform a detailed
      characterization of SSc esophageal histopathology and molecular signatures at the
      level of gene expression. METHODS: Esophageal biopsies were prospectively
      obtained during esophagogastroduodenoscopy in 16 consecutive SSc patients and 7
      subjects without SSc. Upper and lower esophageal biopsies were evaluated for
      histopathology and gene expression. RESULTS: Individual patient's upper and lower
      esophageal biopsies showed nearly identical patterns of gene expression. Similar
      to skin, inflammatory and proliferative gene expression signatures were
      identified suggesting that molecular subsets are a universal feature of SSc end
      target organ pathology. The inflammatory signature was present in biopsies
      without high numbers of infiltrating lymphocytes. Molecular classification of
      esophageal biopsies was independent of SSc skin subtype, serum autoantibodies and
      esophagitis. CONCLUSIONS: Proliferative and inflammatory molecular gene
      expression subsets in tissues from patients with SSc may be a conserved,
      reproducible component of SSc pathogenesis. The inflammatory signature is
      observed in biopsies that lack large inflammatory infiltrates suggesting that
      immune activation is a major driver of SSc esophageal pathogenesis.

PMID- 26220548
TI  - Training in addiction medicine should be standardised and scaled up.

PMID- 26220547
TI  - An Online Documentary Film to Motivate Quit Attempts Among Smokers in the General
      Population (4Weeks2Freedom): A Randomized Controlled Trial.
AB  - INTRODUCTION: Online motivational films to promote quit attempts could encourage
      large numbers of smokers to stop at low unit cost. We evaluated an online film
      documenting the experiences of smokers who recorded the first month of their
      successful attempts to quit (4Weeks2Freedom). The film was designed to boost
      motivation and self-efficacy and provide role-models to promote ex-smoker
      identities. METHODS: This was a randomized trial with individual assignment to a
      no-intervention control (n = 1016), an informational film (n = 1004), or
      4Weeks2Freedom (n = 999). The development of 4Weeks2Freedom was informed by PRIME
      theory and focus-group testing with smokers. The 90-minute film was available
      online to view in one sitting or as chapters over 4 weeks to coincide with the
      progress of an attempt. The primary outcome was a quit attempt in the 4 weeks
      between assignment and study endpoint by intent-to-treat. RESULTS: Participants
      smoked a mean of 13 cigarettes per day and 31% reported not wanting to stop. At
      follow-up, 55% reported viewing the informational control film and 56% viewing
      4Weeks2Freedom. There was no detectable effect compared with the no-intervention
      control (OR = 0.99, 95% CI = 0.81 to 1.21, 24.3% vs. 24.5%) or informational
      control film (OR = 0.99, 95% CI = 0.80 to 1.21, 24.3% vs. 24.6%). Calculation of
      Bayes factors ruled out insensitive data and indicated the intervention was no
      more effective than either the no-intervention control (Bayes factor = 0.20) or
      informational control film (Bayes factor = 0.27). The pattern of results was
      unchanged in sensitivity analyses that examined the effect among only those who
      viewed the films. CONCLUSION: The online documentary film (4Weeks2Freedom)
      designed to boost motivation and self-efficacy and to promote ex-smoker identity
      does not appear to prompt quit attempts among smokers. IMPLICATIONS: This trial
      found that an online documentary film (4Weeks2Freedom) designed to boost
      motivation and self-efficacy and to promote ex-smoker identity was ineffective in
      prompting quit attempts among an unselected panel of smokers from the UK. This
      approach appears unpromising as a means of raising the rate at which smokers
      attempt to quit and is a low priority for future research.

PMID- 26220549
TI  - Direct formation of large-scale multi-layered germanene on Si substrate.
AB  - Germanene layers with lonsdaleite structure has been synthesized from a SiGe thin
      film for the first time using a N2 plasma-assisted process in this investigation.
      Multi-layered germanene can be directly observed, and the derived lattice
      parameters are nearly consistent with the theoretical results. Furthermore, large
      scale multi-layered germanene has also been demonstrated for applications. 

PMID- 26220551
TI  - [Therapy of Pulmonary Arterial Hypertension].
AB  - Pulmonary hypertension (PH) is classified into five distinct groups according to
      the fifth world conference in Nice 2013. Pulmonary arterial hypertension (PAH)
      comprises idiopathic PAH, hereditary PAH, drug-induced and associated PAH. Right
      heart catheterization is essential for the diagnosis of PH and should precede
      initiation of a targeted PAH therapy. Besides general measures and supportive
      therapy, four different classes of targeted drugs have been approved for the
      treatment of PAH. Combination therapy, either sequential or initial (up-front),
      is increasingly gaining recognition. Risk stratification and treatment goals have
      been defined to guide therapeutic decisions. However, cure is still far from
      reach and lung transplantation is an important treatment option for patients with
      end-stage disease under optimal supportive and targeted drug therapy. 

PMID- 26220550
TI  - Global transcriptome and gene regulation network for secondary metabolite
      biosynthesis of tea plant (Camellia sinensis).
AB  - BACKGROUND: Major secondary metabolites, including flavonoids, caffeine, and
      theanine, are important components of tea products and are closely related to the
      taste, flavor, and health benefits of tea. Secondary metabolite biosynthesis in
      Camellia sinensis is differentially regulated in different tissues during growth
      and development. Until now, little was known about the expression patterns of
      genes involved in secondary metabolic pathways or their regulatory mechanisms.
      This study aimed to generate expression profiles for C. sinensis tissues and to
      build a gene regulation model of the secondary metabolic pathways. RESULTS: RNA
      sequencing was performed on 13 different tissue samples from various organs and
      developmental stages of tea plants, including buds and leaves of different ages,
      stems, flowers, seeds, and roots. A total of 43.7 Gbp of raw sequencing data were
      generated, from which 347,827 unigenes were assembled and annotated. There were
      46,693, 8446, 3814, 10,206, and 4948 unigenes specifically expressed in the buds
      and leaves, stems, flowers, seeds, and roots, respectively. In total, 1719
      unigenes were identified as being involved in the secondary metabolic pathways in
      C. sinensis, and the expression patterns of the genes involved in flavonoid,
      caffeine, and theanine biosynthesis were characterized, revealing the dynamic
      nature of their regulation during plant growth and development. The possible
      transcription factor regulation network for the biosynthesis of flavonoid,
      caffeine, and theanine was built, encompassing 339 transcription factors from 35
      families, namely bHLH, MYB, and NAC, among others. Remarkably, not only did the
      data reveal the possible critical check points in the flavonoid, caffeine, and
      theanine biosynthesis pathways, but also implicated the key transcription factors
      and related mechanisms in the regulation of secondary metabolite biosynthesis.
      CONCLUSIONS: Our study generated gene expression profiles for different tissues
      at different developmental stages in tea plants. The gene network responsible for
      the regulation of the secondary metabolic pathways was analyzed. Our work
      elucidated the possible cross talk in gene regulation between the secondary
      metabolite biosynthetic pathways in C. sinensis. The results increase our
      understanding of how secondary metabolic pathways are regulated during plant
      development and growth cycles, and help pave the way for genetic selection and
      engineering for germplasm improvement.

PMID- 26220552
TI  - Massilia arvi sp. nov., isolated from fallow-land soil previously cultivated with
      Brassica oleracea, and emended description of the genus Massilia.
AB  - A novel bacterial strain, designated THG-RS2OT, was isolated from fallow-land
      soil previously cultivated with Brassica oleracea in Yongin, South Korea. Cells
      were Gram-stain-negative, aerobic, non-motile rods, catalase- and oxidase
      positive. Strain THG-RS2OT grew optimally at 25-37  degrees C, at pH 7.0 and in
      the absence of NaCl. 16S rRNA gene sequence analysis demonstrated that strain THG
      RS2OT shows highest sequence similarity with Massilia kyonggiensis KACC 17471T
      followed by Massilia aerilata KACC 12505T, Massilia niastensis KACC 12599T,
      Massilia tieshanensis KACC 14940T and Massilia haematophila KCTC 32001T. Levels
      of DNA-DNA relatedness between strain THG-RS2OT and the closest phylogenetic
      neighbours were below 55.0 % and the DNA G+C content of strain THG-RS2OT was 63.2
      mol%. Major fatty acids were C16 : 0, cyclo-C17 : 0 and summed feature 3 (C16 :
      1omega6c and/or C16 : 1omega7c). The major respiratory quinone was identified as
      ubiquonone-8 and predominant polar lipids were determined to be
      diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol.
      Characterization by 16S rRNA gene sequence analysis, DNA-DNA hybridization,
      ubiquinone, polar lipid, fatty acid composition, and physiological and
      biochemical parameters revealed that strain THG-RS2OT represents a novel species
      of the genus Massilia. Hence, the present study describes a novel species for
      which the name Massilia arvi sp. nov. is proposed. The type strain is THG-RS2OT (
      = KCTC 42609T = CCTCC AB 2015115T).

PMID- 26220554
TI  - Dietary patterns for meals of Brazilian adults.
AB  - The use of dietary patterns (DP) in nutritional research is well established;
      however, only a few studies of DP according to specific meals have been
      conducted. The purpose of this study was to identify the DP regarding breakfast,
      lunch and dinner meals of the population (aged 20 years and older of both sexes)
      that participated in the Health Care Survey of Sao Paulo. Food intake was
      estimated by using the Multiple Source Method - considering two 24- h dietary
      recalls. On the basis of the food groups for each meal, a factor analysis, with a
      principal component estimation, was applied (varimax rotation) in order to derive
      the DP. Prevalences of meal skipping were 5.6 % for breakfast, 3.6 % for lunch
      and 12.8 % for dinner. The findings revealed three breakfast DP: healthy,
      traditional and snack; five lunch DP: traditional, salad, sweetened juice,
      Western and meats; and four dinner DP: coffee with milk and bread, transitional,
      traditional, and soup and fruits. The results of this study indicate that the DP
      identified in accordance with the meal nicely discriminates food intake,
      emphasising peculiarities that are not found in global analyses and might support
      dietary advice. 

PMID- 26220553
TI  - Health related quality of life in patients with actinic keratosis--an
      observational study of patients treated in dermatology specialist care in
      Denmark.
AB  - BACKGROUND: Actinic keratosis (AK) is a common skin condition that may progress
      to non-melanoma skin cancer (NMSC). The disease may influence Health Related
      Quality of Life (HRQoL), but studies of HRQoL in patients with AK are limited.
      The purpose of the study was to analyze HRQoL in patients with different severity
      levels of AK treated in dermatology specialist care using generic and disease
      specific HRQoL instruments and to analyze their relationship. METHODS: AK
      patients who visited dermatological clinics in Denmark were included in an
      observational, cross-sectional, study in a multi-center setting. Dermatologists
      assessed AK severity and patients completed: Actinic Keratosis Quality of Life
      Questionnaire (AKQoL), Dermatology Life Quality Index (DLQI), and EQ-5D-5 L
      including EQ-VAS. Differences between categorical subgroups were tested with
      Wilcoxon rank-sum test. The relationship between instruments was analyzed with
      the Spearman correlation test. RESULTS: A total of 312 patients were included in
      the analyses. Patients reported impairment in the disease specific HRQoL
      instrument AKQoL (mean AKQoL 6.7, DLQI 2, EQ-5D-5 L 0.88, and EQ-VAS 79). HRQoL
      was least affected in patients with mild actinic disease, whereas patients with
      severe actinic damage suffered from further impaired HRQoL (mean AKQoL 10.1 and
      DLQI 4.6). Correlations between DLQI and AKQoL were moderate, whereas the
      correlations between DLQI and EQ-5D-5 L and between AKQoL and EQ-5D-5 L were
      weak. CONCLUSIONS: Patients with severe actinic damage showed more impairment in
      HRQoL than those with mild disease. Correlations between instruments suggest that
      they are complementary as they measure different aspects of HRQoL and are used
      for different purposes.

PMID- 26220556
TI  - Overview of maternal and perinatal mortality in Sudan.
AB  - The Millennium Development Goals (MDGs), agreed on by world leaders at a UN
      summit in 2000, set targets to achieve by 2015. MDGs 4 and 5 specifically focus
      on the health of women and children. Sudan is classified as having insufficient
      progress in achieving MDGs 4 and 5. Both local and international efforts are
      needed to improve maternal and perinatal mortality rates. Ultrasound is expected
      to have a positive impact on improving maternal and perinatal mortality. 

PMID- 26220555
TI  - Exploring the relation between childhood trauma, temperamental traits and
      mindfulness in borderline personality disorder.
AB  - BACKGROUND: Deficits in mindfulness-related capacities have been described in
      borderline personality disorder (BPD). However, little research has been
      conducted to explore which factors could explain these deficits. This study
      assesses the relationship between temperamental traits and childhood maltreatment
      with mindfulness in BPD. METHODS: A total of 100 individuals diagnosed with BPD
      participated in the study. Childhood maltreatment was assessed using the
      Childhood Trauma Questionnaire (CTQ-SF), temperamental traits were assessed using
      the Zuckerman-Khulman Personality Questionnaire (ZKPQ), and mindfulness
      capabilities were evaluated with the Five Facet Mindfulness Questionnaire (FFMQ).
      RESULTS: Hierarchical regression analyses were performed including only those CTQ
      SF and ZKPQ subscales that showed simultaneous significant correlations with
      mindfulness facets. Results indicated that neuroticism and sexual abuse were
      predictors of acting with awareness; and neuroticism, impulsiveness and sexual
      abuse were significant predictors of non-judging. Temperamental traits did not
      have a moderator effect on the relationship between childhood sexual abuse and
      mindfulness facets. CONCLUSIONS: These results provide preliminary evidence for
      the effects of temperamental traits and childhood trauma on mindfulness
      capabilities in BPD individuals. Further studies are needed to better clarify the
      impact of childhood traumatic experiences on mindfulness capabilities and to
      determine the causal relations between these variables.

PMID- 26220557
TI  - Ultrastructural characters of the spermatozoa in Digeneans of the genus Bianium
      Stunkard, 1930 (Digenea, Lepocreadiidae) parasites of fishes: a comparative study
      of Bianium plicitum and Bianium arabicum.
AB  - We present in this paper the first ultrastructural study of the spermatozoon of
      species of the genus Bianium Stunkard, 1930, namely Bianium plicitum and Bianium
      arabicum belonging to the family Lepocreadiidae. Specimens are parasites of the
      tetraodontid teleosts Lagocephalus laevigatus caught in the Atlantic Ocean and
      Lagocephalus sceleratus caught in Pacific Ocean, respectively. Live worms were
      fixed and processed for transmission electron microscopy. Observations of
      numerous cross and longitudinal sections of the spermatozoa of B. plicitum and B.
      arabicum demonstrated the general pattern described in all previously studied
      Lepocreadioidea, namely two axonemes with 9+ "1" pattern of Trepaxonemata, two
      mitochondria, a nucleus, parallel cortical microtubules, and an external
      ornamentation of the plasma membrane associated with spine-like bodies. The
      maximum number of cortical microtubules and the external ornamentation were not
      located at the anterior extremity of the spermatozoon but at a more posterior
      level, as in all the species of Lepocreadioidea studied to date. Differences
      observed between spermatozoa of B. plicitum and B. arabicum were observed in: (1)
      the location of the first mitochondrion, (2) size of cortical microtubules which
      were longer in B. arabicum than in B. plicitum, and (3) the order of the
      disappearance of the axonemes, mitochondrion, and cortical microtubules toward
      the posterior region of the spermatozoon. Only the nucleus reaches into the
      posterior extremity of the spermatozoon in these two species. The general pattern
      of the spermatozoon described in these two species exhibit the general model in
      the genus Bianium. 

PMID- 26220559
TI  - Nematodes parasitizing Trachurus trachurus (L.) and Boops boops (L.) from
      Algeria.
AB  - A total of 455 Boops boops (Linnaeus, 1758) and 953 Trachurus trachurus Linnaeus,
      1758 from the east coast of Algeria were examined for their parasitic Nematoda.
      Two hundred ninety-five specimens of larval stages L3 and L4 were collected from
      the peritoneal cavity of these two examined fishes. Photonic and scanning
      electronic microscopy (SEM) studies were performed on these larvae specimens in
      order to characterize their morphology. Two different species of Nematoda
      (Anisikidae) were identified: Anisakis simplex (Rudolphi, 1809) and
      Hysterothylacium aduncum (Rudolphi, 1802). These two parasitic species were
      reported for the first time on T. trachurus and B. boops from the eastern coast
      of Algeria. These parasites were attached on different organs in the abdominal
      cavity (particularly on ovaries and testes). The infestation rate changed
      according to the month and the host size. The parasitism did not show a
      significant negative impact on the condition of the examined fishes. 

PMID- 26220558
TI  - Incidence of myiasis among humans-a review.
AB  - Myiasis, the infestation of tissues of live humans and other vertebrate animals
      with dipteran larvae (maggots), is a phenomenon of widespread occurrence
      throughout the tropical regions of the world. It is commonly seen in domestic and
      wild animals but occurs rarely in man also. The tissue invasion in man by maggots
      is generally a well-recognized complication of neglected wounds. The condition
      may be asymptomatic but occasionally results in more or less severe problems and
      even death when larvae invade body cavities or areas that forbid their direct
      visual examination. Many cases of myiasis, however, usually do not reach the
      attention of medical practitioners because of the tendency of the mature larvae
      to migrate out of the lesion for pupation. In the present study, the authors
      reviewed the past literature describing the cases of human myiasis, causative fly
      species and predisposing factors for the onset of the same. The aim of the
      present manuscript is to provide a database for the future reference of medical
      entomologists, medical practitioners and veterinarians. Review of literature
      revealed that 37 fly species belonging to ten families were responsible worldwide
      for the onset of human myiasis. The incidence of myiasis among humans can be
      correlated to increasing fly populations, poor hygienic conditions and presence
      of domestic animals in the close vicinity. Other factors responsible for myiasis
      include neglected open wounds and foul-smelling discharge from natural body
      openings. Moreover, ignorance plays a key role in its occurrence since people are
      generally unaware about the actual cause and often correlate the condition to
      their superstitious beliefs. It is emphasized that the patients should not
      neglect their wounds and should take proper medical care; otherwise, myiasis may
      supervene. 

PMID- 26220560
TI  - Host-feeding pattern of Aedes aegypti and Aedes albopictus (Diptera: Culicidae)
      in heterogeneous landscapes of South Andaman, Andaman and Nicobar Islands, India.
AB  - Mosquito foraging behavior is a determinant of host-vector contact and has an
      impact on the risk of arboviral epidemics. Therefore, blood-feeding patterns is a
      useful tool for assessing the role in pathogen transmission by vector mosquitoes.
      Competent vectors of dengue and chikungunya viz. Aedes aegypti and Aedes
      albopictus are widely prevalent in the Andaman and Nicobar archipelago.
      Considering the vector potential, medical importance of both these mosquito
      species and lack of information on host-feeding patterns, blood meal analysis of
      both these vector mosquitoes was undertaken. Biogents Sentinel traps were used
      for sampling blooded mosquitoes, for identifying the source of blood meal by agar
      gel-precipitin test. We identified vertebrate source of 147 and 104 blood meals
      in Ae. aegypti and Ae. albopictus from heterogeneous landscapes in South Andaman
      district. Results revealed that Ae. aegypti (88 %) and Ae. albopictus (49 %) fed
      on human and a small proportion on mammals and fowls, indicative of predominance
      of anthropophilism. Ae. aegypti predominantly fed on human blood (94.2 %-densely
      built urban, 89.8 %-low vegetation coverage, and 78.3 %-medium vegetation
      coverage). Anthropophilism in Ae. albopictus was maximal in densely built urban
      (90.5 %) and progressively decreased from low vegetation-vegetation/forested
      continuum (66.7, 36.4, and 8.7 %), indicating plasticity in feeding across these
      landscapes. Epidemiological significance of the findings is discussed.

PMID- 26220561
TI  - Withdraw or affiliate? The role of humiliation during initiation rituals.
AB  - Initiation rituals can take different forms and empirical evidence is
      inconsistent as to whether these rituals promote affiliation among novices. We
      argue that experienced humiliation during initiations leads to less affiliation
      among novices, in particular when one is initiated as sole group member rather
      than as part of the group. We examined this hypothesis in three studies, using
      different paradigms. In Study 1 (N = 123), perceived severity of an initiation in
      the past was associated with lower affiliation with other novices; this
      relationship was mediated by experienced humiliation. Study 2 (N = 64) showed
      that public derogation in the lab led to more humiliation when participants were
      the only victim than when they were derogated as a group. Study 3 (N = 248), a
      vignette study, showed that a similar effect of social context was mediated by
      expected support from other novices. We conclude that severe initiations may, due
      to experienced humiliation, result in less rather than more affiliation with
      fellow novices. 

PMID- 26220562
TI  - Green Template-Free Synthesis of Hierarchical Shuttle-Shaped Mesoporous ZnFe2 O4
      Microrods with Enhanced Lithium Storage for Advanced Li-Ion Batteries.
AB  - In the work, a facile and green two-step synthetic strategy was purposefully
      developed to efficiently fabricate hierarchical shuttle-shaped mesoporous ZnFe2
      O4 microrods (MRs) with a high tap density of ~0.85 g cm(3) , which were
      assembled by 1D nanofiber (NF) subunits, and further utilized as a long-life
      anode for advanced Li-ion batteries. The significant role of the mixed solvent of
      glycerin and water in the formation of such hierarchical mesoporous MRs was
      systematically investigated. After 488 cycles at a large current rate of 1000 mA
      g(-1) , the resulting ZnFe2 O4 MRs with high loading of ~1.4 mg per electrode
      still preserved a reversible capacity as large as ~542 mAh g(-1) . Furthermore,
      an initial charge capacity of ~1150 mAh g(-1) is delivered by the ZnFe2 O4 anode
      at 100 mA g(-1) , resulting in a high Coulombic efficiency of ~76 % for the first
      cycle. The superior Li-storage properties of the as-obtained ZnFe2 O4 were
      rationally associated with its mesoprous micro-/nanostructures and 1D nanoscaled
      building blocks, which accelerated the electron transportation, facilitated Li(+)
      transfer rate, buffered the large volume variations during repeated
      discharge/charge processes, and provided rich electrode-electrolyte sur
      /interfaces for efficient lithium storage, particularly at high rates.

PMID- 26220563
TI  - Size reduction of cosolvent-infused microbubbles to form acoustically responsive
      monodisperse perfluorocarbon nanodroplets.
AB  - Perfluorocarbon (PFC) nanodroplet agents are exciting new biomaterials that can
      be remotely vapourized by ultrasound or light to change into micron-scale gas
      bubbles in situ. After PFC nanodroplet vapourization, the micron-scale gas bubble
      can interact strongly with ultrasound radiation, such that the bubbles can be
      used for cancer imaging and therapy. For these phase-change agents to be useful,
      however, PFC nanodroplets must be produced in the range of 100 to 400 nm in
      diameter with high size control and monodispersity, restrictions that remain a
      challenge. Here, we address this challenge by taking advantage of the size
      control offered by microfluidics, in combination with the size reduction provided
      by cosolvent-infused PFC bubbles through both condensation and cosolvent
      dissolution. In this approach, PFC bubbles with a high percentage of cosolvent
      (in this study, diethyl ether, DEE) are produced using microfluidics at a
      temperature above the boiling point. After synthesis, these bubbles become much
      smaller through both condensation of the gas into liquid droplets and from
      dissolution of the DEE into the continuous phase. This approach demonstrates that
      monodisperse, cosolvent-incorporated PFC bubbles can directly form monodisperse
      PFC nanodroplets a factor of 24 times smaller than the precursor bubbles. We also
      demonstrate that these nanoscale droplets can be converted to echogenic
      microbubbles after exposure to ultrasound, showing that these PFC nanodroplets
      are viable for the in situ production of ultrasound contrast agents. We show that
      this system can overcome the minimum droplet size limit of standard
      microfluidics, and is a powerful new tool for generating monodisperse, PFC phase
      change ultrasound contrast agents for treating and imaging cancer. 

PMID- 26220564
TI  - A Web-Based Adolescent Positive Psychology Program in Schools: Randomized
      Controlled Trial.
AB  - BACKGROUND: Adolescent mental health is characterized by relatively high rates of
      psychiatric disorders and low levels of help-seeking behaviors. Existing mental
      health programs aimed at addressing these issues in adolescents have repeated
      inconsistent results. Such programs have generally been based on techniques
      derived from cognitive behavioral therapy, which may not be ideally suited to
      early intervention among adolescent samples. Positive psychology, which seeks to
      improve well-being rather than alleviate psychological symptoms, offers an
      alternative approach. A previous community study of adolescents found that
      informal engagement in an online positive psychology program for up to 6 weeks
      yielded significant improvements in both well-being and depression symptoms.
      However, this approach had not been trialed among adolescents in a structured
      format and within a school setting. OBJECTIVE: This study examines the
      feasibility of an online school-based positive psychology program delivered in a
      structured format over a 6-week period utilizing a workbook to guide students
      through website content and interactive exercises. METHODS: Students from four
      high schools were randomly allocated by classroom to either the positive
      psychology condition, "Bite Back", or the control condition. The Bite Back
      condition consisted of positive psychology exercises and information, while the
      control condition used a series of non-psychology entertainment websites. Both
      interventions were delivered online for 6 hours over a period of 4-6 weeks during
      class time. Symptom measures and measures of well-being/flourishing and life
      satisfaction were administered at baseline and post intervention. RESULTS: Data
      were analyzed using multilevel linear modeling. Both conditions demonstrated
      reductions in depression, stress, and total symptom scores without any
      significant differences between the two conditions. Both the Bite Back and
      control conditions also demonstrated significant improvements in life
      satisfaction scores post intervention. However, only the control condition
      demonstrated significant increases in flourishing scores post intervention.
      CONCLUSIONS: Results suggest that a structured online positive psychology program
      administered within the school curriculum was not effective when compared to the
      control condition. The limitations of online program delivery in school settings
      including logistic considerations are also relevant to the contradictory findings
      of this study. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry: ACTRN1261200057831;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362489 (Archived
      by Webcite at http://www.webcitation.org/6NXmjwfAy).

PMID- 26220565
TI  - Putting corannulene in its place. Reactivity studies comparing corannulene with
      other aromatic hydrocarbons.
AB  - A series of aromatic hydrocarbons were investigated so as to compare the
      reactivity of corannulene with planar aromatic hydrocarbons. Corannulene was
      found to be more reactive than benzene, naphthalene and triphenylene to Friedel
      Crafts acylation whilst electrophilic aromatic bromination was also used to
      confirm that triphenylene was less reactive than corannulene and that pyrene,
      perylene and acenaphthene were more so. The stabilisation of a neighbouring
      carbocation by the various aromatic systems was investigated through
      consideration of the rates of methanolysis of a series of benzylic alcohols. The
      reactivity series was found to parallel that observed for the electrophilic
      aromatic substitutions and both series are supported by computational studies. As
      such, a reactivity scale was devised that showed that corannulene was less
      reactive than would be expected for an aromatic planar species of similar pi
      electron count. 

PMID- 26220566
TI  - Coffee consumption and risk of hypertension in the Polish arm of the HAPIEE
      cohort study.
AB  - BACKGROUND/OBJECTIVES: Coffee consumption has been hypothesized to be associated
      with blood pressure (BP), but previous findings are not homogeneous. The aim of
      this study was to evaluate the association between coffee consumption and the
      risk of developing hypertension. SUBJECTS/METHODS: Data on coffee consumption, BP
      and use of anti-hypertensive medicament were derived from 2725 participants of
      the Polish arm of the HAPIEE project (Health, Alcohol and Psychosocial factors In
      Eastern Europe) who were free of hypertension at baseline and followed up for an
      average of 5 years. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated by multivariate logistic regression analyses and stratified for
      potential confounding factors. RESULTS: Coffee consumption was related to
      decreased age, smoking status and total energy intake. Compared with persons who
      drink <1 cup coffee per day, systolic BP was significantly associated with coffee
      consumption and the risk of hypertension was lower for individuals consuming 3-4
      cups per day. Despite the analysis stratified by gender showed that the
      protective effect of coffee consumption on hypertension was significant only in
      women, the analysis after stratification by smoking status revealed a decreased
      risk of hypertension in non-smokers drinking 3-4 cups of coffee per day in both
      sexes (OR 0.41, 95% CI: 0.21, 0.79 for men and OR 0.54, 95% CI: 0.29, 0.99 for
      women). Upper category coffee consumption (>4 cups per day) was not related to
      significant increased risk of hypertension. CONCLUSIONS: Relation between coffee
      consumption and incidence of hypertension was related to smoking status.
      Consumption of 3-4 cups of coffee per day decreased the risk of hypertension in
      non-smoking men and women only.

PMID- 26220567
TI  - Dietary diversity score and obesity: a systematic review and meta-analysis of
      observational studies.
AB  - BACKGROUND/OBJECTIVES: Studies examining the association between dietary
      diversity score (DDS) and obesity have led to inconsistent findings. Therefore,
      the purpose of this review is to summarize and elucidate the source of
      heterogeneous results reported in different studies. METHODS: PubMed, ISI Web of
      Science, Scopus and Google Scholar were searched through December 2013 to
      identify all relevant articles. Sixteen publications met the inclusion criteria
      for the systematic review and 10 articles were entered into the meta-analysis.
      Eight studies had data on the odds ratio (OR) for overweight/obesity and eight
      compared the mean body mass index (BMI) among subjects with highest versus the
      lowest DDS. RESULTS: A meta-analysis on eligible studies failed to show a
      significant association on either overweight/obesity OR (OR: 0.72; 95% confidence
      interval (CI): 0.45-1.16; P=0.174) or mean differences (MD) in BMI (MD: 0.22; 95%
      CI: -0.70-1.14; P=0.643) comparing the highest and lowest diverse diets. Between
      study heterogeneity was high, and subgroup analysis failed to identify the source
      of heterogeneity. CONCLUSIONS: Our systematic review and meta-analysis showed
      that there was no significant association between DDS and BMI status, which may
      be due to use of different methods for assessing dietary intake and determination
      of DDS. Thus, well-designed prospective studies with similar approaches to assess
      DDS are highly recommended.

PMID- 26220568
TI  - The associations of alcohol, coffee and tobacco consumption with gait in a
      community-dwelling population.
AB  - BACKGROUND/OBJECTIVES: Gait is an important health indicator, relating strongly
      to the risk of falling, morbidity and mortality. In a community-dwelling
      population, we investigated associations of alcohol, coffee and tobacco
      consumption with gait. SUBJECTS/METHODS: Two thousand forty-six non-demented
      participants from the Rotterdam Study underwent gait assessment by electronic
      walkway. We measured gait velocity and Global Gait, which is the average of seven
      gait domains: Rhythm, Phases, Variability, Pace, Tandem, Turning and Base of
      Support. Alcohol, coffee and tobacco consumption was assessed by questionnaires.
      With analysis of covariance, we investigated associations of consumption of
      alcoholic beverages, coffee consumption and smoking with Global Gait, gait
      velocity and the seven individual gait domains. RESULTS: In all, 81.9% of
      participants drank alcohol, 92.4% drank coffee, 17.3% were current smokers and
      50.9% were past smokers. Moderate alcohol consumption (1-3 glasses per day)
      associated with better gait, as measured by Global Gait (0.20 standard deviations
      (s.d.) (95% confidence interval: 0.10; 0.31)), gait velocity (2.65 cm/s (0.80;
      4.50)), Rhythm and Variability. Consuming high amounts of coffee (>3 cups per
      day) associated with better Global Gait (0.18 s.d. (0.08; 0.28)), gait velocity
      (2.63 cm/s (0.80; 4.45)), Pace, Turning and Variability. Current smoking
      associated with worse Global Gait (-0.11 s.d. (-0.21; 0.00)), gait velocity (
      3.47 cm/s (-5.33; -1.60)), Rhythm and Pace, compared with non-smokers.
      CONCLUSIONS: In a community-dwelling population, consuming >1 cup of coffee and 1
      3 glasses of alcohol relate to better gait, whereas smoking is related to worse
      gait. Further studies are required to evaluate whether interventions targeting
      substance consumption may aid to prevent or reduce gait deterioration and thereby
      related health problems.

PMID- 26220569
TI  - Plausible self-reported dietary intakes in a residential facility are not
      necessarily reliable.
AB  - BACKGROUND/OBJECTIVES: Comparing reported energy intakes with estimated energy
      requirements as multiples of basal metabolic rate (Ein:BMR) is an established
      method of identifying implausible food intake records. The present study aimed to
      examine the validity of self-reported food intakes believed to be plausible.
      SUBJECTS/METHODS: One hundred and eighty men and women were provided with all
      food and beverages for two consecutive days in a residential laboratory setting.
      Subjects self-reported their food and beverage intakes using the weighed food
      diary method (WDR). Investigators covertly measured subjects' actual consumption
      over the same period. Subjects also reported intakes over four consecutive days
      at home. BMR was measured by indirect calorimetry. RESULTS: Average reported
      energy intakes were significantly lower than actual intakes (11.2 and 11.8 MJ/d,
      respectively, P<0.001). Two-thirds (121) of the WDR were under-reported to
      varying degrees. Only five of these were considered as implausible using an
      Ein:BMR cut-off value of 1.03*BMR. Under-reporting of food and beverage intakes,
      as measured by the difference between reported and actual intake, was evident at
      all levels of Ein;BMR. Reported energy intakes were lower still (10.2 MJ/d) while
      subjects were at home. CONCLUSIONS: Under-recording of self-reported food intake
      records was extensive but very few under-reported food intake records were
      identified as implausible using energy intake to BMR ratios. Under-recording was
      evident at all levels of energy intake.

PMID- 26220570
TI  - Comparison of fruit and vegetable intakes during weight loss in males and
      females.
AB  - BACKGROUND/OBJECTIVES: Globally, fruit and vegetable intakes are well below
      recommendations despite ample evidence to link insufficient intake with increased
      risk of overweight and obesity. Intakes of fruits and vegetables in the general
      population differ between males and females, and although there is growing
      evidence of intakes in men and women during weight loss, evidence that directly
      compares intakes in men and women during weight loss is lacking. This study aimed
      to identify any differences between males and females in fruit and vegetable
      intakes and plasma carotenoid concentrations during weight loss, and determine
      whether there is a relationship between any changes in fruit and vegetable
      intakes and weight change in both males and females. SUBJECTS/METHODS: Men and
      women (n=100; body mass index 25-40 kg/m(2)) aged 18-60 years were selected for
      the study. Dietary intake of fruits and vegetables was assessed using the
      Australian Eating Survey and fasting blood was collected to assess plasma
      carotenoids, which were determined by high-performance liquid chromatography.
      RESULTS: There was little change in fruit or vegetable intakes during weight
      loss, although men tended to increase fruit intakes. Changes in intakes were
      influenced by baseline intakes, with males and females with the highest intakes
      at baseline reducing intakes. Males had better correlations between fruit and
      vegetable intakes and plasma carotenoid concentrations than females, and fruit
      and vegetable intakes during weight loss appear to predict weight loss for males
      but not females. CONCLUSIONS: Fruit and vegetable intake during weight loss does
      not appear to differ largely between males and females.

PMID- 26220571
TI  - Vitamin D in epilepsy: vitamin D levels in epilepsy patients, patients on
      antiepileptic drug polytherapy and drug-resistant epilepsy sufferers.
AB  - The objective of this study was to assess vitamin D levels in epileptic patients
      and to compare its serum levels in patients on antiepileptic monotherapy and
      polytherapy. We analyzed the serum 25-hydroxy (25-OH) vitamin D levels in 98
      consecutive subjects (43 epileptic patients and 55 non-epileptics). Factors
      influencing its serum levels such as degree of sun exposure, physical activity
      and dietary intake were taken into consideration. Overall, 41% had deficient, 49%
      had insufficient and 9% had sufficient levels of serum vitamin D. Elderly
      individuals (>60 years) and people employed in offices and schools had lower
      blood vitamin D levels. Across both the sexes, epileptic patients and non
      epileptics, epileptic patients on monotherapy and polytherapy and patients with
      drug-responsive and -resistant seizures, there were no significant differences in
      serum 25-OH vitamin D levels. Our study shows that people with epilepsy suffer
      with vitamin D deficiency along with their normal peers. 

PMID- 26220572
TI  - Urinary 24-h creatinine excretion in adults and its use as a simple tool for the
      estimation of daily urinary analyte excretion from analyte/creatinine ratios in
      populations.
AB  - BACKGROUND/OBJECTIVES: The assessment of urinary excretion of specific nutrients
      (e.g. iodine, sodium) is frequently used to monitor a population's nutrient
      status. However, when only spot urines are available, always a risk of hydration
      status-dependent dilution effects and related misinterpretations exists. The aim
      of the present study was to establish mean values of 24-h creatinine excretion
      widely applicable for an appropriate estimation of 24-h excretion rates of
      analytes from spot urines in adults. SUBJECTS/METHODS: Twenty-four-hour
      creatinine excretion from the formerly representative cross-sectional German VERA
      Study (n=1463, 20-79 years old) was analysed. Linear regression analysis was
      performed to identify the most important influencing factors of creatinine
      excretion. In a subsample of the German DONALD Study (n=176, 20-29 years old),
      the applicability of the 24-h creatinine excretion values of VERA for the
      estimation of 24-h sodium and iodine excretion from urinary concentration
      measurements was tested. RESULTS: In the VERA Study, mean 24-h creatinine
      excretion was 15.4 mmol per day in men and 11.1 mmol per day in women,
      significantly dependent on sex, age, body weight and body mass index. Based on
      the established 24-h creatinine excretion values, mean 24-h iodine and sodium
      excretions could be estimated from respective analyte/creatinine concentrations,
      with average deviations <10% compared with the actual 24-h means. CONCLUSIONS:
      The present mean values of 24-h creatinine excretion are suggested as a useful
      tool to derive realistic hydration-status-independent average 24-h excretion
      rates from urinary analyte/creatinine ratios. We propose to apply these
      creatinine reference means routinely in biomarker-based studies aiming at
      characterizing the nutrient or metabolite status of adult populations by simply
      measuring metabolite/creatinine ratios in spot urines.

PMID- 26220573
TI  - The value of bioelectrical impedance analysis and phase angle in the evaluation
      of malnutrition and quality of life in cancer patients--a comprehensive review.
AB  - Bioelectrical impedance analysis (BIA) and especially its derived parameter phase
      angle have been widely used in different populations. The variability of BIA
      measures has often been cited as a major limitation for its clinical use in
      evaluating nutritional status and overall health of patients. Cancer patients
      often present with malnourishment and cachexia, which complicate the course of
      treatment and affect outcomes. PubMed, CINAHL, EBSCO and Cochrane Library have
      been searched for relevant publications in English for BIA in cancer patients.
      Out of 197 total results, 27 original research articles related to BIA measures
      in cancer patients were included in this review. Studies indicate that the use of
      BIA and phase angle measures can benefit in the clinical management of cancer
      patients in multiple ways: in the prevention; diagnosis; prognosis; and outcomes
      related to treatments that affect nutritional and overall health status. Phase
      angle and fat-free mass measures were most commonly evaluated and correlated with
      nutritional status and survival rate. One limitation of BIA measures is the high
      interpatient variability which requires careful interpretation of results in the
      context of the individual patient rather than comparison with population data.
      The BIA and phase angle provide practitioners for the evaluation of nutritional
      and overall health status in cancer patients with a convenient and non-invasive
      technique and should be encouraged. 

PMID- 26220574
TI  - CD8+ T cells mediate Chlamydia pneumoniae-induced atherosclerosis in mice.
AB  - Chlamydia pneumoniae is a community-acquired bacterial pathogen that has been
      strongly associated with exacerbation of atherosclerosis. We evaluated the role
      of CD8(+) T cells in the C57BL/6J mouse model of C. pneumoniae-induced
      atherosclerosis. Groups of 4- to 6-week-old male wild-type C57BL/6J (WT) mice and
      mice with a gene deficiency in CD8alpha (CD8 KO mice) were infected with C.
      pneumoniae and fed a high fat (HF) diet. Serum antibody response and serum
      cholesterol were comparable between infected CD8 KO and WT mice. However,
      infected CD8 KO mice displayed significantly reduced atherosclerotic plaque
      lesions on day 100 compared to infected WT mice, at a level comparable to both
      uninfected WT and CD8 KO mice fed the HF diet. Moreover, repletion of CD8 KO mice
      with WT CD8(+) T cells (1 * 10(7) cells/mouse intravenously) at the time of
      infection reverted atherosclerotic plaque lesions to WT levels. These results
      demonstrate that CD8(+) T cells play an important role in mediating C. pneumoniae
      induced exacerbation of atherosclerotic pathology. 

PMID- 26220575
TI  - Cardiovascular responses during cold pressor test are different in Parkinson
      disease and multiple system atrophy with parkinsonism.
AB  - OBJECTIVE: Orthostatic hypotension (OH) is common in Parkinson disease (PD) and
      multiple system atrophy of parkinsonian type (MSA-P), but the pathophysiology of
      OH is different in the two. We hypothesised that the baroreflex-independent
      sympathetic reactivity may also be different in them. To evaluate this we
      assessed the sympathetic vascular reactivity and the heart rate response to the
      standard cold pressor test (CPT) in these patients. METHODS: The study was
      conducted in ten patients with PD with OH, 5 PD without OH, 13 MSA-P with OH, and
      7 MSA-P without OH. Lead II ECG and finger PPG (photoplethysmography) were
      simultaneously acquired during a baseline period of 1 min followed by a 10 
      degrees C cold exposure (1 min) of the contralateral hand (CPT). The vascular
      response was then evaluated by computing the pulse transit time (PTT). RESULTS:
      The percentage decrease in PTT during the CPT was significantly higher in
      patients with PD as compared to MSA-P, irrespective of the presence or absence of
      OH (-2.74 +/- 0.96 vs -0.05 +/- 0.75 %, p = 0.03; PD vs MSA-P with OH and -3.04
      +/- 0.85 vs 0.48 +/- 1.13 %, p = 0.04; PD vs MSA-P without OH). The rise in heart
      rate during CPT was similar in patients with PD and MSA-P with or without OH
      (4.95 +/- 1.6 vs 5.99 +/- 1.04, p = 0.28; PD vs MSA-P with OH and 5.62 +/- 1.31
      vs 13.15 +/- 2.89, p = 0.06; PD vs MSA-P without OH). INTERPRETATION:
      Vasoconstrictor response to CPT is compromised in MSA-P as compared to PD, but
      the baroreflex-independent heart rate response is similar in the two.

PMID- 26220576
TI  - Data sharing in the undiagnosed diseases network.
AB  - The Undiagnosed Diseases Network (UDN) builds on the successes of the Undiagnosed
      Diseases Program at the National Institutes of Health (NIH UDP). Through support
      from the NIH Common Fund, a coordinating center, six additional clinical sites,
      and two sequencing cores comprise the UDN. The objectives of the UDN are to: (1)
      improve the level of diagnosis and care for patients with undiagnosed diseases
      through the development of common protocols designed by an enlarged community of
      investigators across the network; (2) facilitate research into the etiology of
      undiagnosed diseases, by collecting and sharing standardized, high-quality
      clinical and laboratory data including genotyping, phenotyping, and environmental
      exposure data; and (3) create an integrated and collaborative research community
      across multiple clinical sites, and among laboratory and clinical investigators,
      to investigate the pathophysiology of these rare diseases and to identify options
      for patient management. Broad-based data sharing is at the core of achieving
      these objectives, and the UDN is establishing the policies and governance
      structure to support broad data sharing. 

PMID- 26220578
TI  - Asynchronous embryo transfer as a tool to understand embryo-uterine interaction
      in cattle: is a large conceptus a good thing?
AB  - The aim was to examine the effect of embryo-uterine synchrony on conceptus
      elongation and pregnancy rate in cattle. In Study 1, crossbred beef heifers each
      received 10 Day-7 in vitro-produced blastocysts on either Day 5, 7 or 9 after
      oestrus. A proportion of Day 5 recipients were supplemented with progesterone,
      via a progesterone-releasing intravaginal device from Days 3-5 plus either 750IU
      equine chorionic gonadotrophin or 3000IU human chorionic gonadotrophin on Day 3.
      At embryo age Day 14, all heifers were slaughtered and the uterus was flushed.
      Fewer recipients yielded conceptuses (P<0.05) and fewer conceptuses were
      recovered (P<0.05) following transfer on Day 5 compared with Day 7 or 9.
      Supplementation with progesterone resulted in short cycles in approximately 50%
      of recipients. Mean conceptus length was greater (P<0.05) following transfer to
      an advanced uterus. In Study 2, overall pregnancy rate following the fresh
      transfer of a single in vitro-produced blastocyst was 43.5% (2065/4749). Transfer
      of a Day 7 embryo to a synchronous Day-7 uterus resulted in a pregnancy rate of
      47.3%. Transfer to a Day-5 (40.8%) or a Day-8 (41.3%) uterus moderately impacted
      pregnancy rate (P<0.01) while transfer to a uterus 2 days in advance (Day-9,
      24.4%) or 3 days behind (Day-4, 27.0%) reduced (P<0.001) pregnancy rate compared
      with synchronous transfers. In conclusion, transfer of an embryo into an advanced
      uterus results in an acceleration of conceptus development, but does not result
      in greater pregnancy rates.

PMID- 26220577
TI  - Macrophage secretome from women with HIV-associated neurocognitive disorders.
AB  - PURPOSE: Thirty to 50% of HIV patients develop HIV-associated neurocognitive
      disorders (HANDs) despite combined antiretroviral therapy. HIV-1-infected
      macrophages release viral and cellular proteins that induce neuronal degeneration
      and death. We hypothesize that changes in the macrophage secretome of HIV-1
      seropositive patients with HAND may dissect proteins related to neurotoxicity.
      EXPERIMENTAL DESIGN: Monocyte-derived macrophages (MDMs) were isolated from the
      peripheral blood of 12 HIV+ and four HIV- women characterized for neurocognitive
      function. Serum-free MDM supernatants were collected for protein isolation and
      quantification with iTRAQ(r) labeling. Protein identification was performed using
      a LTQ Orbitrap Velos mass spectrometer and validated in MDM supernatants and in
      plasma using ELISA. RESULTS: Three proteins were different between normal
      cognition (NC) and asymptomatic neurocognitive disorders (ANI), six between NC
      and HIV-associated dementia (HAD), and six between NC and HAD. Among these,
      S100A9 was decreased in plasma from patients with ANI, and metalloproteinase 9
      was decreased in the plasma of all HIV+ patients regardless of cognitive status,
      and was significantly reduced in supernatant of MDM isolated from patients with
      ANI. CONCLUSIONS AND CLINICAL RELEVANCE: S100A9 and metalloproteinase 9 have been
      associated with inflammation and cognitive impairment, and therefore represent
      potential targets for HAND treatment.

PMID- 26220579
TI  - Corneal Biofilms: From Planktonic to Microcolony Formation in an Experimental
      Keratitis Infection with Pseudomonas Aeruginosa.
AB  - PURPOSE: Microbial biofilms commonly comprise part of the infectious scenario,
      complicating the therapeutic approach. The purpose of this study was to determine
      in a mouse model of corneal infection if mature biofilms formed and to visualize
      the stages of biofilm formation. METHODS: A bacterial keratitis model was
      established using Pseudomonas aeruginosa ATCC 9027 (1 * 10(8) CFU/ml) to infect
      the cornea of C57BL/6 black mouse. Eyes were examined post-infection (PI) on days
      1, 2, 3, 5, and 7, and imaged by slit lamp microscopy, and light, confocal, and
      electron microscopy to identify the stages of biofilm formation and the time of
      appearance. RESULTS: On PI day 1, Gram staining showed rod-shaped bacteria
      adherent on the corneal surface. On PI days 2 and 3, bacteria were seen within
      webs of extracellular polymeric substance (EPS) and glycocalyx secretion, imaged
      by confocal microscopy. Scanning electron microscopy demonstrated microcolonies
      of active infectious cells bound with thick fibrous material. Transmission
      electron microscopy substantiated the formation of classical biofilm architecture
      with P. aeruginosa densely packed within the extracellular polymeric substances
      on PI days 5 and 7. CONCLUSION: Direct visual evidence showed that biofilms
      routinely developed on the biotic surface of the mouse cornea. The mouse model
      can be used to develop new approaches to deal therapeutically with biofilms in
      corneal infections.

PMID- 26220580
TI  - Pharmacophore-based discovery of inhibitors of a novel drug/proton antiporter in
      human brain endothelial hCMEC/D3 cell line.
AB  - BACKGROUND AND PURPOSE: An influx drug/proton antiporter of unknown structure has
      been functionally demonstrated at the blood-brain barrier. This transporter,
      which handles some psychoactive drugs like diphenhydramine, clonidine, oxycodone,
      nicotine and cocaine, could represent a new pharmacological target in drug
      addiction therapy. However, at present there are no known drugs/inhibitors that
      effectively inhibit/modulate this transporter in vivo. EXPERIMENTAL APPROACH: The
      FLAPpharm approach was used to establish a pharmacophore model for inhibitors of
      this transporter. The inhibitory potency of 44 selected compounds was determined
      against the specific substrate, [(3)H]-clonidine, in the human cerebral
      endothelial cell line hCMEC/D3 and ranked as good, medium, weak or non-inhibitor.
      KEY RESULTS: The pharmacophore model obtained was used as a template to screen
      xenobiotic and endogenous compounds from databases [Specs, Recon2, Human
      Metabolome Database (HMDB), human intestinal transporter database], and
      hypothetical candidates were tested in vitro to determine their inhibitory
      capacity with [(3)H]-clonidine. According to the transporter database, 80% of the
      proton antiporter inhibitor candidates could inhibit P-glycoprotein/MDR1/ABCB1
      and specificity is improved by reducing inhibitor size/shape and increasing water
      solubility. Virtual screening results using HMDB and Recon2 for endogenous
      compounds appropriately scored tryptamine as an inhibitor. CONCLUSIONS AND
      IMPLICATIONS: The pharmacophore model for the proton-antiporter inhibitors was a
      good predictor of known inhibitors and allowed us to identify new good
      inhibitors. This model marks a new step towards the discovery of this drug/proton
      antiporter and will be of great use for the discovery and design of potent
      inhibitors that could potentially help to assess and validate its pharmacological
      role in drug addiction in vivo.

PMID- 26220581
TI  - Inferring 3D chromatin structure using a multiscale approach based on
      quaternions.
AB  - BACKGROUND: The knowledge of the spatial organisation of the chromatin fibre in
      cell nuclei helps researchers to understand the nuclear machinery that regulates
      DNA activity. Recent experimental techniques of the type Chromosome Conformation
      Capture (3C, or similar) provide high-resolution, high-throughput data consisting
      in the number of times any possible pair of DNA fragments is found to be in
      contact, in a certain population of cells. As these data carry information on the
      structure of the chromatin fibre, several attempts have been made to use them to
      obtain high-resolution 3D reconstructions of entire chromosomes, or even an
      entire genome. The techniques proposed treat the data in different ways, possibly
      exploiting physical-geometric chromatin models. One popular strategy is to
      transform contact data into Euclidean distances between pairs of fragments, and
      then solve a classical distance-to-geometry problem. RESULTS: We developed and
      tested a reconstruction technique that does not require translating contacts into
      distances, thus avoiding a number of related drawbacks. Also, we introduce a
      geometrical chromatin chain model that allows us to include sound biochemical and
      biological constraints in the problem. This model can be scaled at different
      genomic resolutions, where the structures of the coarser models are influenced by
      the reconstructions at finer resolutions. The search in the solution space is
      then performed by a classical simulated annealing, where the model is evolved
      efficiently through quaternion operators. The presence of appropriate constraints
      permits the less reliable data to be overlooked, so the result is a set of
      plausible chromatin configurations compatible with both the data and the prior
      knowledge. CONCLUSIONS: To test our method, we obtained a number of 3D chromatin
      configurations from Hi-C data available in the literature for the long arm of
      human chromosome 1, and validated their features against known properties of gene
      density and transcriptional activity. Our results are compatible with biological
      features not introduced a priori in the problem: structurally different regions
      in our reconstructions highly correlate with functionally different regions as
      known from literature and genomic repositories.

PMID- 26220582
TI  - A woman with primary biliary cirrhosis and hyponatremia.

PMID- 26220583
TI  - Commentary.

PMID- 26220584
TI  - Commentary.

PMID- 26220585
TI  - Normal potassium in the presence of gross hemolysis.

PMID- 26220586
TI  - A low-power and high-potential smartphone diagnostic.

PMID- 26220588
TI  - Migration and culture.

PMID- 26220589
TI  - On the interpretation and relevance of the Fundamental Theorem of Natural
      Selection.
AB  - The attempt to understand the statement, and then to find the interpretation, of
      Fisher's "Fundamental Theorem of Natural Selection" caused problems for
      generations of population geneticists. Price's (1972) paper was the first to lead
      to an understanding of the statement of the theorem. The theorem shows (in the
      discrete-time case) that the so-called "partial change" in mean fitness of a
      population between a parental generation and an offspring generation is the
      parental generation additive genetic variance in fitness divided by the parental
      generation mean fitness. In the continuous-time case the partial rate of change
      in mean fitness is equal to the parental generation additive genetic variance in
      fitness with no division by the mean fitness. This "partial change" has been
      interpreted by some as the change in mean fitness due to changes in gene
      frequency, and by others as the change in mean fitness due to natural selection.
      (Fisher variously used both interpretations.) In this paper we discuss these
      interpretations of the theorem. We indicate why we are unhappy with both. We also
      discuss the long-term relevance of the Fundamental Theorem of Natural Selection,
      again reaching a negative assessment. We introduce and discuss the concept of
      genic evolutionary potential. We finally review an optimizing theorem that
      involves changes in gene frequency, the additive genetic variance in fitness and
      the mean fitness itself, all of which are involved in the Fundamental Theorem of
      Natural Selection, and which is free of the difficulties in interpretation of the
      Fundamental Theorem of Natural Selection. 

PMID- 26220590
TI  - 3'-Phosphoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) knockdown sensitizes
      non-small cell lung cancer cells to DNA damaging agents.
AB  - Standard treatment for advanced non-small cell lung cancer (NSCLC) with no known
      driver mutation is platinum-based chemotherapy, which has a response rate of only
      30-33%. Through an siRNA screen, 3'-phosphoadenosine 5'-phosphosulfate (PAPS)
      synthase 1 (PAPSS1), an enzyme that synthesizes the biologically active form of
      sulfate PAPS, was identified as a novel platinum-sensitizing target in NSCLC
      cells. PAPSS1 knockdown in combination with low-dose (IC10) cisplatin reduces
      clonogenicity of NSCLC cells by 98.7% (p < 0.001), increases DNA damage, and
      induces G1/S phase cell cycle arrest and apoptosis. PAPSS1 silencing also
      sensitized NSCLC cells to other DNA crosslinking agents, radiation, and
      topoisomerase I inhibitors, but not topoisomerase II inhibitors. Chemo
      sensitization was not observed in normal epithelial cells. Knocking out the
      PAPSS1 homolog did not sensitize yeast to cisplatin, suggesting that sulfate
      bioavailability for amino acid synthesis is not the cause of sensitization to DNA
      damaging agents. Rather, sensitization may be due to sulfation reactions involved
      in blocking the action of DNA damaging agents, facilitating DNA repair, promoting
      cancer cell survival under therapeutic stress or reducing the bioavailability of
      DNA damaging agents. Our study demonstrates for the first time that PAPSS1 could
      be targeted to improve the activity of multiple anticancer agents used to treat
      NSCLC. 

PMID- 26220591
TI  - Surrogate modeling of deformable joint contact using artificial neural networks.
AB  - Deformable joint contact models can be used to estimate loading conditions for
      cartilage-cartilage, implant-implant, human-orthotic, and foot-ground
      interactions. However, contact evaluations are often so expensive computationally
      that they can be prohibitive for simulations or optimizations requiring thousands
      or even millions of contact evaluations. To overcome this limitation, we
      developed a novel surrogate contact modeling method based on artificial neural
      networks (ANNs). The method uses special sampling techniques to gather input
      output data points from an original (slow) contact model in multiple domains of
      input space, where each domain represents a different physical situation likely
      to be encountered. For each contact force and torque output by the original
      contact model, a multi-layer feed-forward ANN is defined, trained, and
      incorporated into a surrogate contact model. As an evaluation problem, we created
      an ANN-based surrogate contact model of an artificial tibiofemoral joint using
      over 75,000 evaluations of a fine-grid elastic foundation (EF) contact model. The
      surrogate contact model computed contact forces and torques about 1000 times
      faster than a less accurate coarse grid EF contact model. Furthermore, the
      surrogate contact model was seven times more accurate than the coarse grid EF
      contact model within the input domain of a walking motion. For larger input
      domains, the surrogate contact model showed the expected trend of increasing
      error with increasing domain size. In addition, the surrogate contact model was
      able to identify out-of-contact situations with high accuracy. Computational
      contact models created using our proposed ANN approach may remove an important
      computational bottleneck from musculoskeletal simulations or optimizations
      incorporating deformable joint contact models. 

PMID- 26220593
TI  - Optimizing selection with several constraints in poultry breeding.
AB  - Poultry breeding schemes permanently face the need to control the evolution of
      coancestry and some critical traits, while selecting for a main breeding
      objective. The main aims of this article are first to present an efficient
      selection algorithm adapted to this situation and then to measure how the
      severity of constraints impacted on the degree of loss for the main trait,
      compared to BLUP selection on the main trait, without any constraint. Broiler dam
      and sire line schemes were mimicked by simulation over 10 generations and
      selection was carried out on the main trait under constraints for coancestry and
      for another trait, antagonistic with the main trait. The selection algorithm was
      a special simulated annealing (adaptative simulated annealing (ASA)). It was
      found to be rapid and able to meet constraints very accurately. A constraint on
      the second trait was found to induce an impact similar to or even greater than
      the impact of the constraint on coancestry. The family structure of selected
      poultry populations made it easy to control the evolution of coancestry at a
      reasonable cost but was not as useful for reducing the cost of controlling
      evolution of the antagonistic traits. Multiple constraints impacted almost
      additively on the genetic gain for the main trait. Adding constraints for several
      traits would therefore be justified in real life breeding schemes, possibly after
      evaluating their impact through simulated annealing. 

PMID- 26220603
TI  - Efficient removal of crystal violet using Fe3O4-coated biochar: the role of the
      Fe3O4 nanoparticles and modeling study their adsorption behavior.
AB  - Biochar shows great promise for use in adsorbing pollutants. However, a process
      for enhancing its adsorption capacity and re-collection efficiency is yet to be
      further developed. Hence, in this study, we developed a type of biochar coated
      with magnetic Fe3O4 nanoparticles (i.e., magnetic biochar (MBC)) and assessed its
      use for crystal violet (CV) adsorption as well as its recycling potential. The
      coating of Fe3O4 nanoparticles, which was not only on the surface, but also in
      the interior of biochar, performed two functions. Firstly, it produced a
      saturation magnetization of 61.48 emu/g, which enabled the biochar being
      efficiently re-collected using a magnet. Secondly, it significantly enhanced the
      adsorption capacity of the biochar (from 80.36 to 99.19 mg/g). The adsorption
      capacity of the MBC was determined to be the largest by so far (349.40 mg/g) for
      an initial CV concentration of 400 mg/L, pH of 6.0, and temperature of 40 
      degrees C, and the adsorption capacity of re-collected MBC was 73.31 mg/g. The
      adsorption of CV by the MBC was found to be a spontaneous and endothermic
      physical process in which the intraparticle diffusion was the limiting step.
      These findings inspire us to use other similar materials to tackle the menace of
      pollutions. 

PMID- 26220592
TI  - Missouri Mothers and Their Children: A Family Study of the Effects of Genetics
      and the Prenatal Environment.
AB  - The Missouri Mothers and Their Children Study (MO-MATCH) was specifically
      designed to critically investigate prenatal environmental influences on child
      attention problems and associated learning and cognitive deficits. The project
      began as a pilot study in 2004 and was formally launched in 2008. Participants in
      the study were initially identified via the Department of Vital Statistics birth
      record (BR) database. Interview and lab-based data were obtained from: (1)
      mothers of Missouri-born children (born 1998-2005), who smoked during one
      pregnancy but not during another pregnancy; (2) biological fathers when
      available; and (3) the children (i.e., full sibling pairs discordant for exposure
      to maternal smoking during pregnancy (SDP). This within-mother, between-pregnancy
      contrast provides the best possible methodological control for many stable
      maternal and familial confounding factors (e.g., heritable and socio-demographic
      characteristics of the mother that predict increased probability of SDP). It also
      controls for differences between mothers who do and do not smoke during
      pregnancy, and their partners, that might otherwise artifactually create, or
      alternatively mask, associations between SDP and child outcomes. Such a design
      will therefore provide opportunities to determine less biased effect sizes while
      also allowing us to investigate (on a preliminary basis) the possible
      contribution of paternal or other second-hand smoke exposure during the pre,
      peri, and postnatal periods to offspring outcome. This protocol has developed a
      cohort that can be followed longitudinally through periods typically associated
      with increased externalizing symptoms and substance used initiation. 

PMID- 26220604
TI  - Multifunctional T Lymphocytes Generated After Therapy With an Antitumor
      Gallotanin-Rich Normalized Fraction Are Related to Primary Tumor Size Reduction
      in a Breast Cancer Model.
AB  - Natural compounds are promising sources for anticancer therapies because of their
      multifunctional activity and low toxicity. Although the host immune response (IR)
      is clearly implicated in tumor control, the relationship between natural
      therapies and IR has not yet been elucidated. The present work evaluates IR
      induction after treatment with a gallotannin-rich fraction from Caesalpinia
      spinosa (P2Et). Breast tumor 4T1 cells were used to evaluate antitumor properties
      and IR activation. Apoptosis and expression of immunogenic cell death (ICD)
      markers were assessed in vitro, whereas IR and postvaccination tumor evolution
      were assessed in vivo. P2Et fraction induced apoptotic cell death, displaying
      phosphatidylserine externalization and DNA fragmentation. ICD markers such as
      calreticulin, high-mobility group box 1 translocation from nuclei to cytoplasm,
      and ATP secretion were observed. Primary tumor control was improved by
      vaccination with P2Et-pretreated 4T1 cells (t-P2Et), yielding long-lasting ex
      vivo multifunctional CD4(+) and CD8(+) T lymphocytes (interleukin [IL]-2(+),
      tumor necrosis factor [TNF]-alpha(+), interferon [IFN]-gamma(+)) that secrete IL
      2, TNF-alpha, IL-4, IL-5, and IFN-gamma after specific 4T1 cell stimulation. The
      present study constitutes the first demonstration of a long-lasting antitumor IR
      induction and primary tumor reduction induced by a complex natural fraction.
      These data reveal the potential use of this fraction as an adjuvant in breast
      cancer treatment. 

PMID- 26220605
TI  - Acupuncture for Aromatase Inhibitor-Induced Arthralgia: A Systematic Review.
AB  - BACKGROUND: Aromatase inhibitors (AIs) are commonly used as adjunctive hormone
      treatment for early breast cancer patients. The major side effect of AIs is
      arthralgia, which affects adherence. Previous reviews suggested that acupuncture
      is effective in the management of cancer-related pain. The aim of this review is
      to evaluate the effects of acupuncture on arthralgia caused by AIs. METHODS: This
      article examined randomized controlled trials (RCTs) measuring the effects of
      acupuncture on joint symptoms caused by AIs within 8 medical databases till May
      2014. The quality of the articles was evaluated according to the Cochrane risk of
      bias (ROB) tool. RESULTS: Four RCTs were identified in medical journals. Two
      studies were conducted with manual acupuncture and 2 studies were
      electroacupuncture. The range of sample size was between 32 and 67. One RCT
      showed significant improvement in the acupuncture group compared with the sham
      control group and another RCT showed a statistical difference between the
      electroacupuncture and waitlist group. The other 2 studies showed no statistical
      differences between control and acupuncture groups. Two studies conducted blood
      analysis to elucidate the mechanism of efficacy of acupuncture for arthralgia.
      The 2 positive studies had a lower ROB and 2 studies had a high ROB. CONCLUSIONS:
      The systematic review suggests that acupuncture has potential benefits to improve
      arthralgia caused by AIs. However, further trials of adequate sample size,
      appropriate control group, and longer follow-up are necessary to investigate the
      efficacy of acupuncture in AI-induced arthralgia.

PMID- 26220606
TI  - Translational neurophysiology of Parkinson's disease: can't blink on an eye
      blink.

PMID- 26220607
TI  - Carbon accumulation and sequestration of lakes in China during the Holocene.
AB  - Understanding the responses of lake systems to past climate change and human
      activity is critical for assessing and predicting the fate of lake carbon (C) in
      the future. In this study, we synthesized records of the sediment accumulation
      from 82 lakes and of C sequestration from 58 lakes with direct organic C
      measurements throughout China. We also identified the controlling factors of the
      long-term sediment and C accumulation dynamics in these lakes during the past 12
      ka (1 ka = 1000 cal yr BP). Our results indicated an overall increasing trend of
      sediment and C accumulation since 12 ka, with an accumulation peak in the last
      couple of millennia for lakes in China, corresponding to terrestrial organic
      matter input due to land-use change. The Holocene lake sediment accumulation rate
      (SAR) and C accumulation rate (CAR) averaged (mean +/- SE) 0.47 +/- 0.05 mm yr(
      1) and 7.7 +/- 1.4 g C m(-2)  yr(-1) in China, respectively, comparable to the
      previous estimates for boreal and temperate regions. The SAR for lakes in the
      East Plain of subtropical China (1.05 +/- 0.28 mm yr(-1) ) was higher than those
      in other regions (P < 0.05). However, CAR did not vary significantly among
      regions. Overall, the variability and history of climate and anthropogenic
      interference regulated the temporal and spatial dynamics of sediment and C
      sequestration for lakes in China. We estimated the total amount of C burial in
      lakes of China as 8.0 +/- 1.0 Pg C. This first estimation of total C storage and
      dynamics in lakes of China confirms the importance of lakes in land C budget in
      monsoon-influenced regions. 

PMID- 26220608
TI  - The docking of chiral analytes on proline-based chiral stationary phases: A
      molecular dynamics study of selectivity.
AB  - Molecular dynamics simulations are employed to examine the selectivity of four
      proline-based chiral stationary phases in two solvent environments, a relatively
      apolar n-hexane/2-propanol solvent and a polar water/methanol solvent. The four
      chiral surfaces are based on a BOC-terminated diproline, a TMA-terminated
      diproline, a TMA-terminated triproline and a TMA-terminated hexaproline. This
      range of chiral selectors allows an analysis of the impact of oligomer length and
      terminal group on selectivity while the two solvent environments indicate the
      impact of solvent hydrogen bonding and polarity. The selector-analyte
      interactions are examined for six closely related analytes that each have an
      aromatic moiety, a hydrogen, and an alcohol group directly bonded to the
      stereocenter. The analytes differ in the nature of the aromatic group (phenyl or
      anthracyl), in the attachment point (to the central ring or a side ring in the
      anthracyl), and in the fourth group bonded to the carbon (CH3, CF3, or C2H5). For
      each of the 48 solvent+selector+analyte systems, selectivity factors are
      calculated and, when possible, compared to experiment. The docking mode for these
      proline-based selectors is analyzed. 

PMID- 26220609
TI  - Maternal obesity and physical activity and exercise levels as pregnancy advances:
      an observational study.
AB  - BACKGROUND: Increases in clinical complications associated with maternal obesity
      have generated interest in increasing physical activity (PA) and exercise levels
      as an intervention to improve pregnancy outcomes. AIMS: The objective of this
      study was to examine the relationship between BMI categorisation and PA and
      exercise levels as pregnancy advances. METHODS: This was an observational study
      in a large university maternity hospital. Women were recruited at their
      convenience before they left hospital after delivering a baby weighing 500 g or
      more. They completed a detailed customised physical activity and exercise
      questionnaire. BMI categorisation was based on the measurement of weight and
      height in early pregnancy. RESULTS: Of the 155 women recruited, 42.5 % (n = 66)
      were primigravidas and 10.3 % (n = 16) were smokers. Mean Body Mass Index (BMI)
      was 24.6 kg/m(2) and 14.2 % (n = 22) were obese, based on a BMI >29.9 kg/m(2).
      Overall, women decreased their exercise from an average 194 min (range 0-650 min)
      per week pre-pregnancy to 98 min antenatally (range 0-420 min) (p < 0.0001).
      Obese women exercised least pre-pregnancy and antenatally at 187.5 and 75 min per
      week, respectively, compared with 193.2 and 95.5 min per week in the normal BMI
      group and 239.3 and 106.7 min per week in the overweight group. The mean
      gestation at which all women reduced their activity levels was 29 weeks.
      CONCLUSIONS: We found that women decreased their PA  and exercise levels
      significantly in the third trimester and, thus, in the absence of a medical
      contra-indication there is considerable scope for an exercise intervention to
      improve activity  and exercise levels as pregnancy advances. However, an increase
      in PA levels in obese women needs further studies to determine whether it will
      improve the clinical outcomes for the woman and her offspring.

PMID- 26220610
TI  - A novel 2- and 3-choice touchscreen-based continuous trial-unique nonmatching-to
      location task (cTUNL) sensitive to functional differences between dentate gyrus
      and CA3 subregions of the hippocampus.
AB  - RATIONALE: The touchscreen continuous trial-unique non-matching-to-location task
      (cTUNL) has been developed to optimise a battery of tasks under NEWMEDS (Novel
      Methods leading to New Medication in Depression and Schizophrenia,
      http://www.newmeds-europe.com ). It offers novel task features of both a
      practical and a theoretical nature compared to existing touchscreen tasks for
      spatial working memory. OBJECTIVES: The objective of this study was to determine
      whether the cTUNL task is sufficiently sensitive to differentiate between dentate
      gyrus (DG) and CA3 hippocampal subregion contributions to performance. METHODS:
      The effect of DG and CA3 dysfunction on memory for locations in the cTUNL task
      was tested. Rats were assessed on versions of the task-two-choice and three
      choice-that differed in memory load. Performance was challenged using
      manipulations of delay and the spatial separation between target and sample
      locations. RESULTS: Dysfunction of the DG disrupts performance across both delay
      and spatial separations in two-choice cTUNL when the delay is variable and
      unpredictable. Increasing the working memory load (three stimuli) increases
      sensitivity to DG dysfunction, with deficits apparent at fixed, short delays. In
      contrast, CA3 dysfunction did not disrupt performance. CONCLUSION: Acquisition of
      cTUNL was rapid, and the task was sensitive to manipulations of delays and
      separations. A three-choice version of the task was found to be viable. Finally,
      both the two- and three-choice versions of the task were able to differentiate
      between limited dysfunction to different areas within the hippocampus. DG
      dysfunction affected performance when using unpredictable task parameters. CA3
      dysfunction did not result in impairment, even at the longest delays tested.

PMID- 26220611
TI  - Altered performance in a rat gambling task after acute and repeated alcohol
      exposure.
AB  - RATIONALE: A bidirectional relationship between alcohol use disorder (AUD) and
      deficits in impulse control and decision making has been suggested. However, the
      mechanisms by which neurocognitive impairments predispose to, or result from AUD
      remain incompletely understood. OBJECTIVES: The aim of this study is to gain more
      insight in the effects of alcohol exposure on decision making and impulse
      control. We used two modified versions of the rat gambling task (rGT) that differ
      in the net gain and the punishment magnitude associated with the different
      response options. METHODS: In experiment 1, we assessed the effects of acute
      alcohol treatment (0-0.8 g/kg) on rGT performance. In experiment 2, we determined
      the effects of alcohol on rGT acquisition (15 sessions, 0.6 g/kg). Next, these
      animals were challenged with alcohol (0-1.0 g/kg) prior to rGT sessions. RESULTS:
      Acute alcohol treatment suppressed baseline performance in both rGT versions but
      only modestly altered decision making. Treatment with alcohol during acquisition
      increased risky choices in the rGT version that involved larger punishment and
      blunted the reduction in win-shift behavior during acquisition in both rGT
      versions. Moreover, rats treated with alcohol during acquisition showed an
      increase in premature and perseverative responding upon subsequent alcohol
      challenges (0-1.0 g/kg) and were less sensitive to the behavioral suppressant
      effects of alcohol. CONCLUSIONS: Our results show that repeated alcohol exposure
      alters decision making during rGT acquisition and reduces the ability to adjust
      choice behavior on the basis of feedback. In addition, repeated alcohol exposure
      unmasks its behavioral disinhibitory effects in the rGT. Impaired responsiveness
      to choice feedback and behavioral disinhibition may contribute to the development
      of AUD.

PMID- 26220613
TI  - The charge/discharge mechanism and electrochemical performance of CuV2O6 as a new
      anode material for Li-ion batteries.
AB  - The charge/discharge mechanism of CuV2O6 as the anode for Li-ion batteries is
      studied for the first time, suggesting a phase transition in discharging, which
      initially involves the formation of LiV2O5 and Cu3V2O8, the subsequent transition
      from Cu3V2O8 to LixV2O5 and CuO, the insertion of lithium ions into LiV2O5, and
      later the reduction of CuO into Cu. The phase transition of Cu3V2O8 is
      accompanied by an amorphization process, which is maintained in the subsequent
      discharging and charging processes. The CuV2O6/natural graphite electrode with a
      sodium alginate binder is prepared, which shows superior electrochemical
      performance. At a specific current of 110 mA g(-1), it delivers initial discharge
      and charge capacities of 725 and 453 mA h g(-1), respectively, maintaining 537
      and 533 mA h g(-1) after 200 cycles. 

PMID- 26220614
TI  - Laparoscopic repair of voluminous symptomatic hiatal hernia using absorbable
      synthetic mesh.
AB  - INTRODUCTION: Hiatal hernia is a common disorder and a controversial topic. In
      symptomatic voluminous hernias laparoscopic surgery and use of mesh can be
      considered. An initial experience in voluminous hiatal hernia laparoscopic repair
      using absorbable glycolic acid/trimethylene carbonate synthetic mesh is reported.
      MATERIAL AND METHODS: Retrospective study from an institutional database was
      performed to analyze laparoscopic hiatal hernia repair using absorbable synthetic
      mesh from January 2010 to December 2013. All preoperative symptoms and exams were
      collected and a standardized procedure was performed. Clinical and radiological
      follow-up was performed. RESULTS: Eight patients underwent laparoscopic repair of
      hiatal hernia performed by two highly skilled laparoscopic surgeons. One Toupet
      and seven Nissen fundoplications were tailored. No conversions into laparotomy,
      neither intraoperative complications nor mortality occurred. After a median
      follow-up of 23.5 months (range 14 - 44) no mesh complications occurred and all
      patients are asymptomatic. Two radiological recurrences (25%) were detected.
      CONCLUSIONS: Voluminous symptomatic hiatal hernias can be successfully treated in
      a high-volume and long-term experienced laparoscopic surgical center by the use
      of an absorbable synthetic mesh. Further studies and a longer-term follow-up are
      necessary to confirm this preliminary report.

PMID- 26220612
TI  - Genetic influences on delay discounting in smokers: examination of a priori
      candidates and exploration of dopamine-related haplotypes.
AB  - RATIONALE: Delay discounting is a behavioral economic index of impulsivity that
      reflects a person's relative preference for small immediate rewards versus larger
      delayed rewards. Elevated delay discounting is robustly linked to addictive
      disorders and has been increasingly investigated as a viable endophenotype for
      genetic influences on addiction. OBJECTIVE: The aim of this study is to examine
      associations between delay discounting and two a priori loci, rs4680 in COMT and
      rs1800497 in ANKK1, and three exploratory haplotypes proximal to rs1800497 in a
      sample of daily smokers. METHODS: Participants were 713 (60.2 % male) daily
      smokers of European ancestry who completed a delay discounting assessment and
      provided a DNA sample. RESULTS: Significant associations were detected between
      greater discounting of medium magnitude rewards (~$55) and the G allele of
      rs4680, as well as the T allele of rs1800497. Exploratory haplotype analyses
      identified two haplotypes (rs1160467/rs1800497; rs6277/rs1079597) significantly
      associated with delay discounting rates. However, the rs1160467/rs1800497
      haplotype associations appeared to be entirely attributable to variation in
      rs1800497, suggesting that the association of rs1800497 with discounting is best
      understood at the individual SNP level. Similarly, the rs6277/rs1079597 haplotype
      findings suggested that the association was specific to rs1079597. CONCLUSIONS:
      This study provides further evidence that rs4680 and rs1800497 genotypes are
      significantly associated with delay discounting preferences and does so among
      smokers for the first time. The study also provides evidence of specificity for
      the rs1800497 association and identifies a novel locus, rs1079597, as a genetic
      contributor to higher delay discounting rates.

PMID- 26220616
TI  - Inhibitors of Ceramidases.
AB  - The topic of ceramidases has experienced an enormous boost during the last few
      years. Ceramidases catalyze the degradation of ceramide to sphingosine and fatty
      acids. Ceramide is not only the central hub of sphingolipid biosynthesis and
      degradation, it is also a key molecule in sphingolipid signaling, promoting
      differentiation or apoptosis. Acid ceramidase inhibition sensitizes certain types
      of cancer to chemo- and radio-therapy and this is suggestive of a role of acid
      ceramidase inhibitors as chemo-sensitizers which can act synergistically with
      chemo-therapeutic drugs. In this review, we summarize the development of ceramide
      analogues as first-generation ceramidase inhibitors together with data on their
      activity in cells and disease models. Furthermore, we describe the recent
      developments that have led to highly potent second-generation ceramidase
      inhibitors that act at nanomolar concentrations. In the third part, various
      assays of ceramidases are described and their relevance for accurately measuring
      ceramidase activities and for the development of novel inhibitors is highlighted.
      Besides potential clinical implications, the recent improvements in ceramidase
      inhibition and assaying may help to better understand the mechanisms of ceramide
      biology. 

PMID- 26220615
TI  - Interaction of myoglobin with oleic acid.
AB  - Previous studies have shown that palmitate (PA) can interact with myoglobin (Mb).
      The present study has investigated the interaction of the more soluble
      unsaturated fatty acid, oleic acid (OA). Indeed, (1)H NMR measurements of the Mb
      signal during OA titration also show signal changes consistent with specific and
      non-specific binding. At OA:Mb ratio<4:1, OA perturbs selectively the 8-heme
      methyl signal, consistent with a local and specific fatty acid-protein
      interaction. As OA:Mb ratio increases from 4:1 to 40:1, all hyperfine shifted
      MbCN signals decrease, consistent with a non-selective, global perturbation of
      the protein. The pH titration analysis indicates that the observed OA methylene
      signal in the presence of Mb reflects a non-specific interaction and does not
      originate from a shift in the lamella-micelle equilibrium. Given the OA
      interaction with Mb, a fatty acid flux model suggests that Mb can play a fatty
      acid transport role under certain physiological conditions. 

PMID- 26220617
TI  - Life in 3D is never flat: 3D models to optimise drug delivery.
AB  - The development of safe, effective and patient-acceptable drug products is an
      expensive and lengthy process and the risk of failure at different stages of the
      development life-cycle is high. Improved biopharmaceutical tools which are
      robust, easy to use and accurately predict the in vivo response are urgently
      required to help address these issues. In this review the advantages and
      challenges of in vitro 3D versus 2D cell culture models will be discussed in
      terms of evaluating new drug products at the pre-clinical development stage.
      Examples of models with a 3D architecture including scaffolds, cell-derived
      matrices, multicellular spheroids and biochips will be described. The ability to
      simulate the microenvironment of tumours and vital organs including the liver,
      kidney, heart and intestine which have major impact on drug absorption,
      distribution, metabolism and toxicity will be evaluated. Examples of the
      application of 3D models including a role in formulation development,
      pharmacokinetic profiling and toxicity testing will be critically assessed.
      Although utilisation of 3D cell culture models in the field of drug delivery is
      still in its infancy, the area is attracting high levels of interest and is
      likely to become a significant in vitro tool to assist in drug product
      development thus reducing the requirement for unnecessary animal studies. 

PMID- 26220618
TI  - Antimicrobial N-brominated hydantoin and uracil grafted polystyrene beads.
AB  - Hydantoin-N-halamine derivatives conjugated on polystyrene beads are promising
      disinfectants with broad antimicrobial activity affected by the gradual release
      of oxidizing halogen in water. The objective of this work was to identify and
      test of hydantoin-like molecules possessing urea moiety, which may provide N
      haloamines releasing oxidizing halogens when exposed to water at different rates
      and release profiles for tailored antimicrobial agents. In this work, several
      hydantoin (five member ring) and for the first time reported, uracil (six member
      ring) derivatives have been conjugated to polystyrene beads and tested for their
      lasting antimicrobial activity. Four molecules of each series were conjugated
      onto polystyrene beads from the reaction of the N-potassium hydantoin or uracil
      derivatives onto chloromethylated polystyrene beads. A distinct difference in
      bromine loading capacity and release profiles was found for the different
      conjugated derivatives. All tested materials exhibit strong antimicrobial
      activity against Escherichia coli and bacteriophages MS2 of 7 and ~4 log
      reduction, respectively. These results highlight the antimicrobial potential of
      halogenated cyclic molecules containing urea groups as water disinfection agents.

PMID- 26220619
TI  - Cooperative interaction of antimicrobial peptides with the interrelated immune
      pathways in plants.
AB  - Plants express a diverse repertoire of functionally and structurally distinct
      antimicrobial peptides (AMPs) which provide innate immunity by acting directly
      against a wide range of pathogens. AMPs are expressed in nearly all plant organs,
      either constitutively or in response to microbial infections. In addition to
      their direct activity, they also contribute to plant immunity by modulating
      defence responses resulting from pathogen-associated molecular pattern/effector
      triggered immunity, and also interact with other AMPs and pathways involving
      mitogen-activated protein kinases, reactive oxygen species, hormonal cross-talk
      and sugar signalling. Such links among AMPs and defence signalling pathways are
      poorly understood and there is no clear model for their interactions. This
      article provides a critical review of the empirical data to shed light on the
      wider role of AMPs in the robust and resource-effective defence responses of
      plants.

PMID- 26220620
TI  - ADAM10 gene expression in the blood cells of Alzheimer's disease patients and
      mild cognitive impairment subjects.
AB  - ADAM10 is a potential biomarker for Alzheimer's disease (AD). ADAM10 protein
      levels are reduced in platelets of AD patients. The aim was to verify the total
      blood and platelet ADAM10 gene expression in AD patients and to compare with mild
      cognitive impairment (MCI) and healthy subjects. No significant differences in
      ADAM10 gene expression were observed. Therefore, the decrease of ADAM10 protein
      in platelets of AD patients is not caused by a reduction in ADAM10 mRNA. Further
      studies must be performed to investigate other pathways in the down regulation of
      ADAM10 protein. 

PMID- 26220621
TI  - Rolf Maximilian Sievert (1896-1966): father of radiation protection.

PMID- 26220622
TI  - International Congress of Clinical Anatomy, 24-27 June 2015, Rouen, France.

PMID- 26220623
TI  - Getting Best Outcomes: Paradigm and Process Matter.

PMID- 26220624
TI  - Melanosis of the areola and nipple with an atypical pigment network.

PMID- 26220625
TI  - Red propolis ameliorates ischemic-reperfusion acute kidney injury.
AB  - INTRODUCTION: Acute kidney injury (AKI) remains a great problem in clinical
      practice. Renal ischemia/reperfusion (I/R) injury is a complex pathophysiological
      process. Propolis is a natural polyphenol-rich resinous substance collected by
      honeybees from a variety of plant sources that has anti-inflammatory and anti
      oxidative properties. Red propolis (RP) protection in renal I/R injury was
      investigated. METHODS: Male Wistar rats underwent unilateral nephrectomy and
      contralateral renal I/R (60 min). Rats were divided into four groups: (1) sham
      group, (2) RP group (sham-operated rats treated with RP), 3) IR group (rats
      submitted to ischemia) and (4) IR-RP (rats treated with RP before ischemia). At
      48 h after reperfusion, renal function was assessed and kidneys were removed for
      analysis. RESULTS: I/R increased plasma levels of creatinine and reduced
      creatinine clearance (CrCl), and RP provided protection against this renal
      injury. Red propolis significantly improves oxidative stress parameters when
      compared with the IR group. Semiquantitative assessment of the histological
      lesions showed marked structural damage in I/R rats compared with the IR-RP rats.
      RP attenuates I/R-induced endothelial nitric oxide-synthase down regulation and
      increased heme-oxygenase expression in renal tissue. CONCLUSION: Red propolis
      protects kidney against acute ischemic renal failure and this protection is
      associated with reduced oxidative stress and eNOS and heme-oxygenase up
      regulation.

PMID- 26220626
TI  - Antiproliferative activity of rosamultic acid is associated with induction of
      apoptosis, cell cycle arrest, inhibition of cell migration and caspase activation
      in human gastric cancer (SGC-7901) cells.
AB  - BACKGROUND: Gastric cancer is the second leading cause of cancer related deaths
      after lung cancer globally. Among natural products, natural triterpenes represent
      a structurally diverse group of organic compounds with potent antitumor activity.
      PURPOSE: The objective of the present research work demonstrated the
      antiproliferative and apoptotic activity of rosamultic acid, a natural
      triterpenoid, in human gastric cancer (SGC-7901) cells. Its effect on cellular
      morphology, cell cycle arrest, DNA fragmentation and expression levels of caspase
      3, caspase-8 and caspase-9 were also determined. METHODS: Antiproliferative
      activity of rosamultic acid was evaluated by MTT assay. Phase contrast,
      fluorescence microscopy as well as flow cytometry using Hoechst 33342, acridine
      orange/ethidium bromide and Annexin V-FITC as cellular probes were used to
      evaluate the induction of apoptosis by rosamultic acid. Protein level expressions
      were analyzed by western blot analysis. RESULTS: The results revealed that
      rosamultic acid induced dose-dependent as well as time dependent cytotoxic
      effects in SGC-7901 gastric cancer cells. It also led to a reduction in
      clonogenic activity along with inhibiting the cell migration. Characteristic
      features of apoptosis induced by rosamultic acid were observed and quantified.
      Cell cycle arrest at sub-G1 phase was induced by rosamultic acid along with
      downregulation of expression levels of CDK4, CDK6 and cyclin D1. Rosamultic acid
      also significantly led to the activation of caspase-3, -8 and -9 during the 48 h
      treatment along with cleaving PARP in a dose-dependent manner. DNA fragmentation
      following rosamultic acid treatment was also observed in these cells. CONCLUSION:
      The current study strongly reveals that rosamultic acid inhibits gastric cancer
      proliferation by inducing apoptosis mediated through cell cycle arrest,
      downregulation of cell cycle related protein expressions, inhibition of cell
      migration, DNA damage, and activation of caspases.

PMID- 26220627
TI  - Tenuigenin enhances hippocampal Schaffer collateral-CA1 synaptic transmission
      through modulating intracellular calcium.
AB  - BACKGROUND: Tenuigenin (TEN), a natural product from the Chinese herb Polygala
      tenuifolia root, has been reported to improve cognitive function and exhibits
      neuroprotective effects in pharmacological studies of the central nervous system.
      Synaptic transmission is the essential process of brain physiological functions
      such as learning and memory formation, and TEN has been shown to facilitate the
      basic synaptic transmission. HYPOTHESIS/PURPOSE: Although our previous work has
      demonstrated that TEN is able to potentiate the basic synaptic transmission, the
      potential mechanism remains unclear. Here we investigated the effect of TEN on
      the synaptic transmission and analysed the potential mechanism. We hope that
      these findings will contribute to explain the role of TEN as a nootropic product
      or neuroprotective drug in the future. METHODS: Field excitatory postsynaptic
      potentials (fEPSPs), spontaneous excitatory postsynaptic currents (sEPSCs) and
      miniature spontaneous excitatory postsynaptic currents (mEPSCs) were recorded, by
      using in vitro field potential electrophysiology and whole-cell patch clamp
      techniques in acute hippocampal slices from rats. RESULTS: TEN perfusion
      significantly enhanced the slope of fEPSPs and reduced the ratio of paired-pulse
      facilitation. Moreover, TEN increased the frequency and amplitude of sEPSCs but
      only improved the frequency of mEPSCs rather than amplitude in hippocampal CA1
      pyramidal neurons. With removal of extracellular calcium, TEN treatment also
      enhanced the mEPSCs frequency without affecting amplitude. Interestingly, the
      increase of mEPSCs frequency caused by TEN was blocked by chelation of
      intracellular calcium with BAPTA-AM. CONCLUSION: These results indicate that TEN
      enhances the basic synaptic transmission via stimulating presynaptic
      intracellular calcium.

PMID- 26220628
TI  - Panax notoginseng saponins suppress radiation-induced osteoporosis by regulating
      bone formation and resorption.
AB  - BACKGROUND: While radiation-based therapies are effective for treating numerous
      malignancies, such treatments can also induce osteoporosis. PURPOSE: We assessed
      the antiosteoporotic properties of total saponins extracted from the leaves of
      Panax notoginseng (LPNS) in a mouse model of radiation-induced osteoporosis and
      in vitro. STUDY DESIGN/METHODS: The bone mineral densities, the marker of bone
      formation and resorption, and inflammatory factors were measured in vivo. Cell
      proliferation and differentiation were detected in vitro. RESULTS: The results
      showed that bone mineral densities in irradiated mice administered LPNS were
      significantly increased compared to those in irradiated mice which had not
      received LPNS. LPNS attenuated the inflammation caused by irradiation, and
      significantly increased blood serum AKP activity, the mRNA levels of RUNX2 and
      osteoprotegerin, and the numbers of CFU-Fs formed by bone marrow cells collected
      from irradiated mice. In contrast, LPNS decreased the numbers of osteoclast
      precursor cells (CD117(+)/RANKL(+) cells and CD71(+)/CD115(+) cells) and the mRNA
      levels of TRAP and ATP6i. These results suggest that LPNS functions as a negative
      regulator of bone resorption. In vitro assays showed that LPNS promoted the
      differentiation of bone marrow mesenchymal stem cells and mononuclear cells into
      osteoblasts and osteoclasts, respectively, but had no effect on osteoclast
      activation. CONCLUSION: These results demonstrate that LPNS has significant
      antiosteoporotic activity, which may warrant further investigations concerning
      its therapeutic effects in treating radiation-induced osteoporosis.

PMID- 26220629
TI  - Different anticancer effects of Saxifragifolin A on estrogen receptor-positive
      and estrogen receptor-negative breast cancer cells.
AB  - BACKGROUND: Breast cancer is the leading cause of cancer-related death among
      women worldwide. For treating breast cancer, numerous natural products have been
      considered as chemotherapeutic drugs. HYPOTHESIS/PURPOSE: The present study aims
      to investigate the apoptotic effect of Saxifragifolin A (Saxi A) isolated from
      Androsace umbellata in two different human breast cancer cells which are ER
      positive MCF-7 cells and ER-negative MDA-MB-231 cells, and examine the molecular
      basis for its anticancer actions. STUDY DESIGN: The inhibitory effects of Saxi A
      on cell survival were examined in MCF-7 cells and MDA-MB-231 cells in vitro.
      METHODS: MTT assays, Annexin V/PI staining analysis, ROS production assay,
      Hoechst33342 staining and Western blot analysis were performed. RESULTS: Our
      results showed that MDA-MB-231 cells were more sensitive to Saxi A-induced
      apoptosis than MCF-7 cells. Saxi A induced apoptosis in MDA-MB-231 cells through
      ROS-mediated and caspase-dependent pathways, whereas treatment with Saxi A
      induced apoptosis in MCF-7 cells in a caspase-independent manner. In spite of
      Saxi A-induced activation of MAPKs in both breast cancer cell lines, only p38
      MAPK and JNK mediated Saxi A-induced apoptosis. In addition, cell survival of
      shERalpha-transfected MCF-7 cells was decreased, while MDA-MB-231 cells that
      overexpress ERalpha remained viable. CONCLUSION: Saxi A inhibits cell survival in
      MCF-7 cells and MDA-MB-231 cells through different regulatory pathway, and
      ERalpha status appears to be important for regulating Saxi A-induced apoptosis in
      breast cancer cells. Thus, Saxi A may have a potential therapeutic use for
      treating breast cancer.

PMID- 26220630
TI  - Aldose reductase inhibition of a saponin-rich fraction and new furostanol saponin
      derivatives from Balanites aegyptiaca.
AB  - BACKGROUND: Balanites aegyptiaca Del. (Zygophyllaceae) fruits are used to treat
      hyperglycemia in Egyptian folk medicine and are sold by herbalists in the
      Egyptian open market for this purpose. Nevertheless, the fruits have not yet been
      incorporated into pharmaceutical dosage forms. The identity of the bioactive
      compounds and their possible mechanisms of action were not well understood until
      now. PURPOSE: Aldose reductase inhibitors are considered vital therapeutic and
      preventive agents to address complications caused by hyperglycemia. The present
      study was carried out to identify the primary compounds responsible for the
      aldose reductase inhibitory activity of Balanites aegyptiaca fruits. STUDY
      DESIGN: The 70% ethanolic extract of Balanites aegyptiaca fruit mesocarp and its
      fractions were screened for inhibition of the aldose reductase enzyme. Bio-guided
      fractionation of the active butanol fraction was performed and the primary
      compounds present in the saponin-rich fraction (D), which were responsible for
      the inhibitory activity, were characterized. HPLC chromatographic profiles were
      established for the different fractions, using the isolated compounds as
      biomarkers. METHODS: Aldose reductase inhibition was tested in vitro on rat liver
      homogenate. The butanol fraction of the 70% ethanolic extract was fractionated
      using vacuum liquid chromatography (VLC, RP-18 column). The most active sub
      fraction D, which was eluted with 75% methanol, was subjected to preparative HPLC
      to isolate the bioactive compounds. RESULTS: The butanol fraction displayed
      inhibitory activity against the aldose reductase enzyme (IC50 = 55.0 +/- 6
      ug/ml). Sub-fraction D exhibited the highest inhibitory activity (IC50 = 12.8 +/-
      1 ug/ml). Five new steroidal saponin derivatives were isolated from this
      fraction. The isolated compounds were identified as compound 1a/b, a 7:3 mixture
      of the 25R:25S epimers of 26-O-beta-D-glucopyranosyl-furost-5-ene-3,22,26-triol 3
      O-[alpha-L-rhamnopyranosyl-(1->3)- beta-D-glucopyranosyl-(1->2)]- alpha-L
      rhamnopyranosyl-(1->4)-beta-D-glucopyranoside; compound 2, 26-O-beta-D
      glucopyranosyl-(25R)-furost-5-ene-3,22,26-triol 3-O-[ beta-D-glucopyranosyl-(1
      >2)]- alpha-L-rhamnopyranosyl-(1->4)-beta-D-glucopyranoside; compound 3, 26-O
      beta-D-glucopyranosyl-(25R)-furost-5,20-diene-3,26-diol 3-O-[alpha-L
      rhamnopyranosyl-(1->3)- beta-D-glucopyranosyl-(1->2)]- alpha-L-rhamnopyranosyl-(1
      >4)-beta-D-glucopyranoside; compound 4, 26-O-beta-D-glucopyranosyl-(25R)-furost
      5,20-diene-3,26-diol 3-O-[ beta-D-glucopyranosyl-(1->2)]- alpha-L-rhamnopyranosyl
      (1->4)-beta-D-glucopyranoside; and compound 5, which is the 25S epimer of
      compound 4, by using various spectroscopic methods [MS,1D and 2D NMR (HSQC, HMBC,
      DQF-COSY, HSQC-TOCSY)]. Compounds 1a/b, 2, 3, 4, 5 exhibited highly significant
      aldose reductase inhibitory activities (IC50 values were 1.9 +/- 0.2, 1.3 +/-
      0.5, 5.6 +/- 0.2, 5.1 +/- 0.4, 5.1 +/- 0.6 uM, respectively) as compared to the
      activity of the reference standard quercetin (IC50 = 6.6 +/- 0.3 uM). CONCLUSION:
      The aldose reductase inhibitory activity of Balanites fruits is due to the
      steroidal saponins present. HPLC chromatographic profiles of the crude butanol
      fraction and its 4 sub-fractions showed that the most highly bioactive fraction D
      contained the highest amount of steroidal saponins (75%) as compared to the 21%
      present in the original butanol fraction. The isolated furostanol saponins proved
      to be highly active in an in vitro assay.

PMID- 26220631
TI  - Two triterpeniods from Cyclocarya paliurus (Batal) Iljinsk (Juglandaceae) promote
      glucose uptake in 3T3-L1 adipocytes: The relationship to AMPK activation.
AB  - PURPOSE: The current study investigated the efficacy of Cyclocarya paliurus
      chloroform extract (CPEC) and its two specific triterpenoids (cyclocaric acid B
      and cyclocarioside H) on the regulation of glucose disposal and the underlying
      mechanisms in 3T3-L1 adipocytes. METHODS: Mice and adipocytes were stimulated by
      macrophages-derived conditioned medium (Mac-CM) to induce insulin resistance.
      CPEC was evaluated in mice for its ability by oral glucose tolerance test (OGTT)
      and insulin tolerance test (ITT). To investigate the hypoglycemic mechanisms of
      CPEC and its two triterpenoids, glucose uptake, AMP-activated protein kinase
      (AMPK) activation, inhibitor of NF-kappaB kinase beta (IKKbeta) phosphorylation
      and insulin signaling transduction were detected in 3T3-L1 adipocytes using 2
      NBDG uptake assay and Western blot analysis. RESULTS: Mac-CM, an inflammatory
      stimulus which induced the glucose and insulin intolerance, increased
      phosphorylation of IKKbeta, reduced glucose uptake and impaired insulin
      sensitivity. CPEC and two triterpenoids improved glucose consumption and
      increased AMPK phosphorylation under basal and inflammatory conditions. Moreover,
      CPEC and its two triterpenoids not only enhanced glucose uptake in an insulin
      independent manner, but also restored insulin-mediated protein kinase B (Akt)
      phosphorylation by reducing the activation of IKKbeta and regulating insulin
      receptor substrate-1 (IRS-1) serine/tyrosine phosphorylation. These beneficial
      effects were attenuated by AMPK inhibitor compound C, implying that the effects
      may be associated with AMPK activation. CONCLUSIONS: CPEC and its two
      triterpenoids promoted glucose uptake in the absence of insulin, as well as
      ameliorated IRS-1/PI3K/Akt pathway by inhibiting inflammation. These effects were
      related to the regulation of AMPK activity.

PMID- 26220632
TI  - Neuroprotective activity and cytotoxic potential of two Parmeliaceae lichens:
      Identification of active compounds.
AB  - BACKGROUND: Lichens are symbiotic organisms capable of producing unique secondary
      metabolites, whose pharmacological activities are attracting much interest.
      PURPOSE: The present study aimed to investigate the in vitro neuroprotective
      effects and anticancer potential of methanol extracts of two Parmeliaceae
      lichens: Cetraria islandica and Vulpicida canadensis. The chemical composition of
      the two lichens was also determined. METHODS: Neuroprotective activity was
      studied with respect to the antioxidant properties of the extracts; radical
      scavenging tests (ORAC and DPPH assays) were performed and oxidative stress
      markers (intracellular ROS production, caspase-3 activity, MDA and glutathione
      levels) were assessed in a hydrogen peroxide-induced oxidative stress model in
      astrocytes. Cytotoxic activity was tested against human HepG2 (hepatocellular
      carcinoma) and MCF-7 (breast adenocarcinoma) cell lines. RESULTS: Cell viability
      studies identified a single concentration for each extract that was subsequently
      used to measure oxidative stress markers. Lichen extracts were able to reverse
      the oxidative damage caused by hydrogen peroxide, thus promoting astrocyte
      survival. Both lichen extracts also had anticancer activity in the cell lines,
      with IC50 values of 19.51-181.05 ug/ml. The extracts had a high total phenolic
      content, and the main constituents identified by HPLC were fumarprotocetraric
      acid in Cetraria islandica, and usnic, pinastric and vulpinic acids in Vulpicida
      canadensis. The biological activities of the lichen extracts can be attributed to
      these secondary metabolites. CONCLUSION: The lichen species studied are promising
      sources of natural compounds with neuroprotective activity and cytotoxic
      potential, and warrant further research.

PMID- 26220633
TI  - Silver fir (Abies alba) trunk extract protects guinea pig arteries from impaired
      functional responses and morphology due to an atherogenic diet.
AB  - BACKGROUND: Diet, rich in plant polyphenols prevents atherogenesis that manifests
      as reduced vascular relaxation and formation of plaques. HYPOTHESIS:
      Atherosclerosis could be reduced by the intake of silver fir (Abies alba) extract
      (SFTE), rich in polyphenols. STUDY DESIGN: Chronic, in vivo treatment animal
      study. METHODS: Guinea pigs (Cavia porcellus) were fed for 8 weeks with one of
      the following three diets: atherogenic, basic or atherogenic + SFTE. After
      isolation, we measured the relaxation and contractile responses of the thoracic
      aorta. Additionally, we measured the area of fatty plaques on the aortic walls.
      RESULTS: Compared to the basic diet, the atherogenic diet decreased the ability
      of the aorta to relax by 63% (p < 0.001). The addition of SFTE to the atherogenic
      diet improved the aorta relaxation response compared to that of the atherogenic
      diet without SFTE (the decrease relative to the basic diet was 26%, p < 0.001).
      The aorta contractility did not differ between the groups. The SFTE group
      generated significantly fewer atherosclerotic plaques than did the atherogenic
      group. The areas of atherosclerotic plaques were 7.4, 0.3 and 1.6% in the aortas
      of guinea pigs receiving atherogenic, basic or atherogenic + SFTE diets,
      respectively. CONCLUSIONS: In a guinea pig model, prolonged treatment with
      antioxidative polyphenol-rich SFTE prevents aortic functional and morphological
      changes caused by an atherogenic diet.

PMID- 26220634
TI  - The germacranolide sesquiterpene lactone neurolenin B of the medicinal plant
      Neurolaena lobata (L.) R.Br. ex Cass inhibits NPM/ALK-driven cell expansion and
      NF-kappaB-driven tumour intravasation.
AB  - BACKGROUND: The t(2;5)(p23;q35) chromosomal translocation results in the
      expression of the fusion protein NPM/ALK that when expressed in T-lymphocytes
      gives rise to anaplastic large cell lymphomas (ALCL). In search of new therapy
      options the dichloromethane extract of the ethnomedicinal plant Neurolaena lobata
      (L.) R.Br. ex Cass was shown to inhibit NPM/ALK expression. PURPOSE: Therefore,
      we analysed whether the active principles that were recently isolated and found
      to inhibit inflammatory responses specifically inhibit growth of NPM/ALK+ ALCL,
      leukaemia and breast cancer cells, but not of normal cells, and the intravasation
      through the lymphendothelial barrier. METHODS: ALCL, leukaemia and breast cancer
      cells, and normal peripheral blood mononuclear cells (PBMCs) were treated with
      isolated sesquiterpene lactones and analysed for cell cycle progression,
      proliferation, mitochondrial activity, apoptosis, protein and mRNA expression, NF
      kappaB and cytochrome P450 activity, 12(S)-HETE production and lymphendothelial
      intravasation. RESULTS: In vitro treatment of ALCL by neurolenin B suppressed
      NPM/ALK, JunB and PDGF-Rbeta expression, inhibited the growth of ALCL cells late
      in M phase, and induced apoptosis via caspase 3 without compromising
      mitochondrial activity (as a measure of general exogenic toxicity). Moreover,
      neurolenin B attenuated tumour spheroid intravasation probably through inhibition
      of NF-kappaB and CYP1A1. CONCLUSION: Neurolenin B specifically decreased pro
      carcinogenic NPM/ALK expression in ALK+ ALCL cells and, via the inhibition of NF
      kB signalling, attenuated tumour intra/extravasation into the lymphatics. Hence,
      neurolenin B may open new options to treat ALCL and to manage early metastatic
      processes to which no other therapies exist.

PMID- 26220635
TI  - Quality of Life and Hormonal, Biochemical, and Anthropometric Profile Between
      Olanzapine and Risperidone Users.
AB  - This cross-sectional study compared quality of life and side effects in 108 users
      of olanzapine or risperidone suffering schizophrenia and being attended at
      psychiatric ambulatory services in Rio Grande do Norte, Brazil. Economic, socio
      demographic, anthropometric, biochemical, and hormonal variables were compared.
      The EuroQoL Five-Dimension Scale (EQ-5D) was used to evaluate quality of life,
      and side effects were assessed using the Udvalg for Kliniske Undersogelser (UKU)
      Side Effect Rating Scale and the Simpson-Angus Scale. Data were analysed using
      the chi(2) test and Student's t test, with a significance level of 5 %.The
      household incomes of approximately 80 % of patients were <2.0 minimum wages
      ($678). Anthropometric variables (waist circumference, hip circumference, weight,
      waist-to-hip ratio) and systolic and diastolic blood pressure were noted among
      male olanzapine users (all p < 0.05). EQ-5D scores showed that olanzapine use
      significantly impacted self-help ability (p < 0.001). Risperidone users had a
      mean quality-adjusted life year value of 1. Mean total Simpson-Angus Scale scores
      was 0.38 for olanzapine users and 0.11 for risperidone users (p < 0.02).
      Significant differences in UKU were observed for the following items:
      asthenia/lassitude/fatigue (higher among olanzapine users, p = 0.02), dystonia
      (higher among olanzapine users, p = 0.01), tremors (higher among olanzapine
      users, p = 0.03), gynecomastia (higher among risperidone users, p < 0.02), and
      ejaculatory dysfunction (higher among risperidone users, p < 0.02). Olanzapine
      users had impaired quality of life, which can be explained in part by adverse
      motor, biochemical, and hormonal effects characteristic of metabolic syndrome.

PMID- 26220636
TI  - Changing Trends in Treatment of Acute Mania: Experience of a Tertiary Centre Over
      a Decade.
AB  - We investigated trends over a decade in the prescription of lithium,
      antiepileptics, and antipsychotic agents at discharge for patients hospitalised
      for acute mania. We conducted a retrospective review of medical records for 165
      inpatients with acute mania who had been hospitalised in Cerrahpasa Faculty of
      Medicine, Department of Psychiatry during 2001-2002 and 2011-2012. Among 165
      patients, prescription of olanzapine at discharge increased from 3 to 46 % (p <
      0.001), while prescription of haloperidol decreased from 55 to 21 % (p < 0.001).
      Use of other atypical antipsychotics did not change significantly (risperidone
      decreased from 14 to 11 %, p = 0.5; quetiapine increased from 10 to 16 %, p =
      0.2). Use of valproate, carbamazepine, and lithium did not change significantly.
      Use of electroconvulsive therapy in acute mania decreased by half from 27 to 13 %
      (p = 0.02). Typical antipsychotics alone or in combination with antiepileptics
      were the most common treatment regimen at discharge at 2001-2002; while 10 years
      later, they had been largely replaced by lithium or antiepileptics combined with
      second generation antipsychotics. Antipsychotic agents remained to be an
      important component of acute treatment of mania in our practice.

PMID- 26220637
TI  - Central blockade of salusin beta attenuates hypertension and hypothalamic
      inflammation in spontaneously hypertensive rats.
AB  - Salusin beta is a multifunctional bioactive peptide and is considered as a
      promising candidate biomarker for predicting atherosclerotic cardiovascular
      diseases. The present study was designed to investigate the roles and mechanisms
      of salusin beta in the paraventricular nucleus (PVN) in attenuating hypertension
      and hypothalamic inflammation and whether central salusin beta blockade has
      protective effects in essential hypertension. Normotensive Wistar-Kyoto (WKY)
      rats and spontaneously hypertensive rats (SHR) were used in this study. The rats
      were chronic PVN infusion either specific salusin beta blocker, antisalusin beta
      IgG (SIgG), or control IgG (CIgG) for 2 weeks. Hypertensive rats had
      significantly increased salusin beta expression compared with normotensive rats.
      Central blockade of salusin beta attenuated hypertension, reduced circulating
      norepinephrine (NE) levels, and improved cardiac hypertrophy and function in
      hypertensive rats. Salusin beta blockade significantly reduced proinflammatory
      cytokines (PICs), nuclear factor-kappa B (NF-kappaB) activity, reactive oxygen
      species (ROS) levels, and altered renin-angiotensin system (RAS) components in
      the PVN of hypertensive rats. These findings suggest that the beneficial effects
      of salusin beta blockade in essential hypertension are possibly due to down
      regulate of inflammatory molecules and ROS in the PVN. 

PMID- 26220638
TI  - Quantification of Drug-Induced Inhibition of Canalicular Cholyl-l-Lysyl
      Fluorescein Excretion From Hepatocytes by High Content Cell Imaging.
AB  - We describe the use of a commercially available high content cell imaging
      algorithm (Cellomics Arrayscan Spot Detector) to quantify biliary excretion of
      the fluorescent probe substrate cholyl-l-lysyl-fluorescein (CLF) from rat
      hepatocytes cultured in collagen/matrigel sandwich configuration and to explore
      inhibition of this process by a variety of test compounds. The method provided
      robust, reproducible data. Twenty-nine pharmaceuticals inhibited biliary CLF
      efflux from hepatocytes and a broad range of potencies of inhibition were
      observed (IC50 values ranged between <1 and 794 uM). Thirteen drugs that
      inhibited CLF efflux also inhibited hepatocellular uptake of the probe substrate
      [(3)H]-taurocholate. Although no clear correlation between the potencies of
      inhibition of the 2 processes was evident, these data highlight the need to
      consider possible uptake transporter inhibition when interpreting hepatocyte CLF
      inhibition data. It has been reported that CLF is transported by MRP2. The CLF
      efflux inhibition data correlated closely with published data on inhibition by
      the drugs of the bile salt export pump (Bsep), which suggests that the tested
      drugs inhibit both Bsep and Mrp2. Calculation of the ratios between the maximum
      human plasma concentrations of the drugs and their CLF efflux inhibition IC50
      values raised the possibility that for many, but not all, of them the in vitro
      effects may be functionally significant in vivo and that Mrp2 inhibition might be
      a drug-induced liver injury (DILI) risk factor. These data indicate that imaging
      hepatocyte CLF inhibition is a promising new method for quantification of biliary
      efflux inhibition by drugs, which could aid assessment of compound-related DILI
      risk.

PMID- 26220639
TI  - Using social media as a strategy to address 'sophomore slump' in second year
      nursing students: A qualitative study.
AB  - INTRODUCTION: An important contributing factor to the shortfall in the nursing
      workforce is the high attrition rate of students from nursing programmes.
      Recently, researchers have begun to examine the 'sophomore slump' phenomenon,
      related to students' sense of low self-efficacy associated with learning in their
      second year of study, that may be related to attrition. BACKGROUND: Academic
      success is heavily influenced by self-efficacy, or a student's belief in their
      ability to be successful. Strategies that enhance self-efficacy include peer
      learning, which increases students' engagement and reinforces self-regulated
      learning. Social networking sites such as Facebook provide students the
      opportunity to take part in peer learning and may promote students' self
      efficacy. AIM: The aim of the study was to develop a Facebook forum that utilised
      peer learning, to build self-efficacy related to learning, of students commencing
      into the second year of a three year nursing programme. METHODS: Students
      commencing into year two of a Bachelor of Nursing programme were invited to join
      a Facebook forum to support their study. One hundred and ninety-eight students
      accepted the invitation. Data was collected over a twelve-week period. Text from
      the Facebook forum was downloaded and analysed thematically. FINDINGS: Analysis
      suggests that Facebook forums may be a useful peer learning strategy to build
      students' self-efficacy related to study in the second year of nursing study.
      Students shared mastery experiences, provided modelling experiences, and used
      verbal persuasion to reframe problems which suggested that it helped build
      students' self-efficacy, and alleviated some of the physiological response
      associated with stress. CONCLUSION: The findings suggest that social media
      platforms are important tools by which students can engage in peer learning to
      build self-efficacy around their nursing studies. This may in part help address
      the 'sophomore slump' phenomenon, enhance students' learning experiences more
      widely, and impact on students' decisions to remain in nursing programmes.

PMID- 26220641
TI  - Bacteria Etiological Agents Causing Lower Respiratory Tract Infections and Their
      Resistance Patterns.
AB  - BACKGROUND: Lower respiratory tract infections (LTRIs) are among the most common
      infectious diseases with potential life-threatening complications. METHODS: The
      study consisted of 426 patients with suspected LTRIs from mid and far western
      region of Nepal between September 2011 and July 2014. The specimens were
      collected and processed according to the standard microbiological methods at the
      Central Laboratory of Microbiology of Nepalgunj Medical College, Nepal. RESULTS:
      Among the isolated Gram-positive organisms, Streptococcus pneumonia (n = 30,
      51.7%) was the most predominant pathogen, followed by Staphylococcus aureus (n =
      28, 48.3%). Among the isolated Gram-negative organisms, Pseudomonas aeruginosa (n
      = 71, 35.32%) was the most predominant pathogen, followed by Haemophilus
      influenzae (n = 68, 33.83%), Klebsiella pneumonia (n = 36, 17.19%), and
      Escherichia coli (n = 26, 12.94%). The pattern of resistance varied regarding the
      bacteria species, and there were multi-resistant isolates. Also, a significant
      difference (P value less than 0.05) was observed between males and females for
      each type of bacterial species. Among 259 isolates, 86 (33.20%) were from
      children aged 1-10 years, which were statistically significant (P valuse less
      than 0.05) compared to the other age groups. CONCLUSIONS: P. aeruginosa and H.
      influenzae (Gram-negative) and S. pnemoniae (Gram-positive) were the most common
      bacterial isolates recovered from LTRIs. Age group of 1-10 years old was at a
      higher risk. Many isolates showed appreciable levels of antibiotic resistance due
      to antibiotic abuse. There is a need to increase surveillance and develop better
      strategies to curb the increasing prevalence of LRTI in this region of Nepal.

PMID- 26220642
TI  - Effects of triploidy incidence on clinical outcomes for IVF-ET cycles in
      different ovarian stimulation protocols.
AB  - PURPOSE: To discuss the relationship between triploidy incidence and clinical
      outcomes of embryos derived from normally fertilized oocytes from the same cohort
      for in vitro fertilization-embryo transfer (IVF-ET) cycles in different ovarian
      stimulation protocol. METHODS: This study included 2070 in vitro fertilization
      (IVF) cycles with long-term protocol, 802 IVF cycles with ultra short-term
      protocol and 508 IVF-D (in vitro fertilization by donor semen) cycles with long
      term protocol from January 2013 to September 2014. According to the different 3PN
      rate, patients were divided into three groups as follows: Group 1 included
      patients with 0% 3PN zygotes, Group 2 included patients with 1-25% 3PN zygotes
      and Group 3 included patients with >25% 3PN zygotes. MAIN OUTCOME MEASURE: female
      age, no. of retrieved oocytes, normal fertilization rate, day-3 grade I + II
      embryos rate, day-3 grade I + II + III embryos rate, implantation rate, pregnancy
      rate and early abortion rate. RESULTS: Triploidy cycle incidence rate in IVF and
      IVF-D cycles with long-term protocol were significantly higher than in IVF cycles
      with ultra short-term protocol (p < 0.001). Triploidy fertilization rate found no
      significant difference between the three groups (p > 0.05). In three protocols,
      normal fertilization rate in 3PN = 0% and 3PN = 1-25% groups were significantly
      higher compared to 3PN > 25% group (p < 0.001). In IVF cycles with long-term
      protocol, the day-3 grade I + II embryos, implantation and pregnancy rate in 3PN
      > 25% group were significantly lower than other two groups (p < 0.05). The day-3
      grade I + II + III embryos and early abortion rate found no significant
      difference between the three groups (p > 0.05). In IVF cycles with ultra short
      term protocol, there were no significant differences found in day-3 grade I + II
      embryos, day-3 grade I + II + III embryos, implantation, pregnancy and early
      abortion rate (p > 0.05). In IVF-D cycles with long-term protocol, the day-3
      grade I + II embryos, day-3 grade I + II + III embryos and implantation rate in
      3PN > 25% group were significantly lower than other two groups (p < 0.05). The
      pregnancy and early abortion rates found no significant difference in the three
      groups (p > 0.05). CONCLUSION: We observed that high proportion of triploid
      zygotes made a negative effect on clinical outcomes for IVF-ET cycles with long
      term protocol.

PMID- 26220640
TI  - Advanced MR Imaging in Neuro-oncology.
AB  - The value of magnetic resonance (MR) imaging for the clinical management of brain
      tumour patients has greatly increased in recent years through the introduction of
      functional MR sequences. Previously, MR imaging for brain tumours relied for the
      most part on contrast-enhanced T1-weighted MR sequences but today with the help
      of advanced functional MR sequences, the pathophysiological aspects of tumour
      growth can be directly visualised and investigated. This article will present the
      pathophysiological background of the MR sequences relevant to neuro-oncological
      imaging as well as potential clinical applications. Ultimately, we take a look at
      possible future developments for ultra-high-field MR imaging. 

PMID- 26220643
TI  - Expression profiling analysis of immune-related genes in channel catfish
      (Ictalurus punctatus) skin mucus following Flavobacterium columnare challenge.
AB  - Fish are covered by a watery gel-mucus, mainly secreted by the goblet cells,
      serving as the physical and biochemical barrier between the external environment
      and the interior milieu, playing more important roles in fish that without scale.
      Despite the important roles of mucus in fish immunity, the knowledge of detailed
      molecular events happened during infection process is still limited. While most
      studies were focused on characterizing the protein and enzyme activities in the
      mucus following challenge, no studies have examined the gene expression profiles
      in fish mucus. In this regard, herein we carried out the first gene profiling
      analysis in catfish mucus using real-time PCR. Ten important immune-related genes
      were selected according to our previous studies. Their expression levels were
      examined in the early timepoints (namely, 1 h, 2 h, 4 h, 8 h, and 24 h) following
      Flavobacterium columnare challenge. Notably, expression levels of most of the
      selected genes were rapidly altered by the challenge. Seven genes were down
      regulated, while only three genes were up-regulated. In addition, the gene
      expression patterns in mucus were very different from the mucosal surfaces (skin,
      gill and intestine) and the classical immune organs (liver, spleen and kidney).
      The unique expression patterns obtained here may be resulted from the great
      advantage of the large amount of attached bacteria in the mucus than the internal
      tissues, and resulted from the bacteria virulent actors to suppress the host
      immune response. Taken together, our results can expand our knowledge of fish
      mucosal immunity, and the un-lethal mucus sampling can provide early insight for
      developing the strategies for selection of disease resistant families and strains
      in catfish as well as other fish species.

PMID- 26220644
TI  - The miR-1000-p53 pathway regulates apoptosis and virus infection in shrimp.
AB  - The p53 protein plays an important role in apoptosis which is involved in the
      immunity of animals. However, effects of the miRNA-mediated regulation of p53
      expression on apoptosis and virus infection are not extensively investigated. To
      address this issue, the miRNA-mediated p53-dependent apoptotic pathway was
      explored in this study. The results indicated that p53 could regulate the
      apoptotic activity of Marsupenaeus japonicas shrimp and influence the infection
      of white spot syndrome virus (WSSV). The further data presented that miR-1000
      could target the 3'-untranslated region (3'UTR) of p53 gene. The results of in
      vivo experiments showed that the miR-1000 overexpression led to significant
      decreases of shrimp apoptotic activity and the capacity of WSSV infection, while
      the miR-1000 silencing resulted in significant increases of apoptotic activity
      and virus infection, indicating that miR-1000 took great effects on apoptosis and
      virus infection by targeting p53. Therefore, our study revealed a novel mechanism
      that the miR-1000-p53 pathway regulated apoptosis and virus infection in shrimp.

PMID- 26220646
TI  - Functional dyspepsia and the Rome criteria: a success story.
AB  - The Rome III criteria for functional dyspepsia (FD), published in 2006,
      immediately generated controversy but have arguably helped to jump start the
      field in terms of mechanistic and therapeutic research. One controversy has
      surrounded the veracity of FD symptom subgroups and their overlap. In clinical
      practice the overlap of postprandial distress syndrome (PDS) and epigastric pain
      syndrome (EPS) is striking. In this issue, results from Belgium suggest overlap
      can be reduced by reclassifying those who have postprandial pain or nausea as
      PDS, and meal-related symptoms predominate in FD. This is consistent with other
      objective experimental observations. The realization most FD occurs postmeal
      ingestion is driving a new conceptualization of the syndrome. For example, the
      observation there is an excess of duodenal eosinophils in PDS has been confirmed,
      with recent observations implicating increased duodenal permeability and immune
      activation. The link between PDS and anxiety, not identified in EPS, provides yet
      further evidence for distinct pathophysiological entities. While symptom-based
      criteria likely need refinement, the recognition of PDS and EPS has promoted
      exciting progress. 

PMID- 26220647
TI  - Rome III functional dyspepsia subdivision in PDS and EPS: recognizing
      postprandial symptoms reduces overlap.
AB  - BACKGROUND: The Rome III consensus proposed to subdivide functional dyspepsia
      (FD) into two groups: meal-related dyspepsia or postprandial distress syndrome
      (PDS), and meal-unrelated dyspepsia or epigastric pain syndrome (EPS). However,
      in clinical practice, overlap between both has been reported to be as high as
      50%, thereby hampering clinical applicability. Although EPS is referred to as
      meal-unrelated dyspepsia, relationship of symptoms to meal ingestion in this
      category is not formally addressed in the Rome III criteria. The aim of our study
      was to investigate whether taking into account the relationship of epigastric
      pain and nausea to meal ingestion may help to improve separation between EPS and
      PDS. METHODS: Consecutive ambulatory tertiary-care patients with epigastric
      symptoms filled out Rome III gastro-duodenal questionnaires with supplementary
      questions. Those fulfilling Rome III FD criteria and a negative endoscopy were
      identified and subdivided into 'pure' PDS patients (i.e., meeting criteria for
      PDS without EPS symptoms), 'pure' EPS (i.e., meeting criteria for EPS without PDS
      symptoms), and overlapping PDS-EPS (i.e., symptoms of both PDS and EPS). KEY
      RESULTS: Out of 1029 patients coming to endoscopy, 199 patients (73% females,
      45.9 +/- 1.0 years, BMI: 23.7 +/- 0.35) fulfilled Rome III FD diagnostic
      criteria, and could be subdivided into pure PDS (69% females, 49 +/- 2 years,
      BMI: 24.2 +/- 0.61), pure EPS (59% females, 47.4 +/- 2 years, BMI: 23.2 +/- 0.97)
      and overlapping PDS-EPS (64% females, age 43 +/- 5 years, BMI: 26 +/- 0.46).
      Compared with pure EPS patients, the overlap PDS-EPS patients were characterized
      by a higher occurrence of postprandial epigastric pain (70% vs 31%, p < 0.0001),
      while the occurrence of epigastric pain in between meals was borderline (48% vs
      38%, p = 0.05). In addition, the overlap PDS-EPS patients reported a higher
      occurrence of postprandial nausea (23% vs 0%, p < 0.0001), and bloating (79% vs
      28%, p = 0.0001). When postprandial epigastric pain and postprandial nausea were
      considered as PDS symptoms, the 'adapted' subdivision identified 48% pure PDS,
      16% pure EPS, and 36% overlapping PDS-EPS patients. CONCLUSIONS & INFERENCES: EPS
      and PDS symptoms frequently coexist in FD patients, with postprandial symptoms
      substantially contributing to the overlap. A more rigorous linking of
      postprandially occurring symptoms to PDS, regardless of their qualitative nature,
      may improve the separation between PDS and EPS.

PMID- 26220648
TI  - Are we underestimating the prevalence of small intestinal bacterial overgrowth in
      irritable bowel syndrome?

PMID- 26220649
TI  - Possible underestimation of SIBO in IBS patients: is lack of Glucose Breath Test
      standardization responsible?

PMID- 26220650
TI  - Development of a cyclodextrin-based aqueous cyclosporin A eye drop formulations.
AB  - Cyclosporin A (CyA) is a lipophilic, cyclic polypeptide drug with anti
      inflammatory properties. It is used in topical treatment of dry eyes and is now
      commercially available in oil based surfactant containing eye drops. Surfactants
      can irritate the eye surface causing burning, itching and irritation of the
      conjunctiva, and oil-based drops can result in blurred vision. Thus, the aim of
      this study was to develop surfactant free aqueous 0.05% (w/v) CyA eye drops where
      the drug is present in an aqueous vehicle containing CyA/cyclodextrin (CyA/CD)
      nanoparticles. The effects of the natural alpha-, beta- and gamma-cyclodextrins
      (alphaCD, betaCD and gammaCD), as well as of the water soluble hydroxypropyl
      derivatives of gammaCD and alphaCD (HPgammaCD, HPalphaCD) and randomly methylated
      betaCD (RMbetaCD), were determined in pure water. alphaCD had the best
      solubilizing effect increasing the solubility of CyA above 0.05% upon addition of
      only 5% (w/v) alphaCD. gammaCD did not have as good solubilizing effect but was
      tested further due to its superior ability to form nanoparticles and its
      favorable toxicological profile. Seven eye drop formulations were prepared and
      tested. All contained 0.05% (w/v) CyA in addition to polyvinyl alcohol,
      benzalkonium chloride, disodium edetate and various amounts of CD (alphaCD,
      gammaCD and mixtures thereof). When the formulation contained only alphaCD most
      of the drug was dissolved but some small aggregates were formed with hydrodynamic
      diameter of about 6 and 155 nm. When the formulation contained only gammaCD
      negligible CyA/CD complexation occurred with most of the drug present as solid
      CyA particles. When the formulation contained a mixture of alphaCD and gammaCD,
      where alphaCD concentration was at least 3% (w/v), the entire drug content was
      dissolved in the media under formation of relatively large (100-2000 nm) CyA/CD
      nanoparticles. alphaCD solubilized the drug while gammaCD enhanced nanoparticle
      formation. The effect of polyvinyl alcohol, benzalkonium chloride and disodium
      edetate on the nanoparticle formation was also investigated and shown to have
      positive effect on the aggregate formation.

PMID- 26220651
TI  - Graphene oxide increases the viability of C2C12 myoblasts microencapsulated in
      alginate.
AB  - Cell microencapsulation represents a great promise for long-term drug delivery,
      but still several challenges need to be overcome before its translation into the
      clinic, such as the long term cell survival inside the capsules. On this regard,
      graphene oxide has shown to promote proliferation of different cell types either
      in two or three dimensions. Therefore, we planned to combine graphene oxide with
      the cell microencapsulation technology. We first studied the effect of this
      material on the stability of the capsules and next we analyzed the
      biocompatibility of this chemical compound with erythropoietin secreting C2C12
      myoblasts within the microcapsule matrix. We produced 160 MUm-diameter alginate
      microcapsules with increasing concentrations of graphene oxide and did not find
      modifications on the physicochemical parameters of traditional alginate
      microcapsules. Moreover, we observed that the viability of encapsulated cells
      within alginate microcapsules containing specific graphene oxide concentrations
      was enhanced. These results provide a relevant step for the future clinical
      application of graphene oxide on cell microencapsulation.

PMID- 26220652
TI  - Patterning poly(maleic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5)
      undecane) copolymer bioconjugates for controlled release of drugs.
AB  - Owing to the special characteristics and abilities polymeric networks have
      received special interest for a range of biomedical applications especially for
      drug delivery systems. This study was devoted to preparation of new polymeric
      compounds based on maleic anhydride and 3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5)
      undecane copolymer (poly maleic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro
      (5.5) undecane) (PMAU) patterned as a network for bioconjugation and tested as
      drug carrier systems. The PMAU copolymer was improved in its functionality by
      opening the maleic anhydride ring with different amounts of erythritol, which is
      free of side effects in regular use and a multifunctional compound, and also
      confers antioxidant character for the new compounds. The new polymeric matrices
      were loaded with acetaminophen, codeine and their fixed dose combinations. The
      investigation demonstrated the capability of the new structures to be used as
      polymer networks for linking bioactive compounds and to perform controlled
      delivery. The physico-chemical investigations--Fourier transform infrared
      spectroscopy (FTIR) spectra, contact angle, zeta potential (ZP - z, PMAU and its
      derivatives samples loaded with medicines present decreased values of zeta
      potential attesting the bioconjugate formation and as well their stability), and
      hydrodynamic radius, near infrared chemical imaging evaluation (new specific
      bands being registered for bio-conjugate with acetaminophen around of 1150-1200
      nm and 1700 nm, and also between 1150 and 1200 nm in case of the codeine bio
      conjugate), scanning electron microscopy (SEM) studies, X-ray diffraction
      analysis--evidenced the formation of the bioconjugates in relation to the
      chemical composition of the polymer matrices, while in vitro release study and in
      vivo tests confirm the capacity for drug delivery of the prepared bioactive
      systems.

PMID- 26220653
TI  - Use of appropriate healthcare technologies: a cross-sectional study in rural
      Zhejiang of China.
AB  - BACKGROUND: Appropriate healthcare technologies (AHTs) are an important strategy
      for improving the availability and accessibility of healthcare services. It is
      not clear what impact AHTs have on health workers and consumers; and whether
      those AHTs can continue in place without special or ongoing financial support.
      This study investigated the attitudes of health workers and consumers towards
      AHTs. METHODS: Health facilities from five counties in Zhejiang were surveyed.
      Participants of the study included all health workers who were involved in the
      delivery of AHTs in the selected organizations and a group of randomly selected
      patients who sought services from the participating organizations. A total of 822
      questionnaires from health workers and 693 questionnaires from patients were
      collected for data analyses. The questionnaires measured perceptions and
      attitudes of respondents towards AHTs using a Likert scale. RESULTS: The
      respondents delivering public health services rated the highest scores to AHTs
      (4.42 +/- 0.7), followed by those engaged in management of chronic conditions
      (4.41 +/- 0.57) and Traditional Chinese Medicine (TCM) (4.29 +/- 0.55). Around
      90% of health workers believed that AHTs were meaningful for rural patients;
      however, only 69% of health workers believed that the technologies encouraged by
      the government were sufficiently developed or "mature", and more than 24%
      acknowledged difficulties in using those technologies. Overall, patients were
      satisfied with AHTs, with 71.6% feeling "very satisfied" or "satisfied", 24.2%
      feeling "acceptable" and 1.6% feeling "dissatisfied". Most (83%) patients were
      satisfied or very satisfied with Traditional Chinese Medicine, compared with
      management of chronic conditions (80%), family planning (67%), public health
      services (64%), and finally with maternal and child health care (59%).
      CONCLUSIONS: Local acceptability should be taken into consideration in
      determination of AHTs; consumer health literacy needs improvement, particularly
      in relation to public health and preventive services.

PMID- 26220654
TI  - Retrospective evaluation of xylitol ingestion in dogs: 192 cases (2007-2012).
AB  - OBJECTIVE: To summarize the signalment, clinical signs, prevalence of decreased
      blood glucose concentration (BG), prevalence of increased liver values,
      treatment, and outcome in dogs known to have ingested xylitol. DESIGN:
      Retrospective study from December 2007 to February 2012 SETTING: Three university
      teaching hospitals. ANIMALS: One hundred ninety-two client-owned dogs with known
      or suspected xylitol ingestion. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The median ingested xylitol dose was 0.32 g/kg (range 0.03-3.64 g/kg).
      Clinical signs were present in 39 (20%) dogs on presentation to the veterinary
      teaching hospitals. The most common clinical sign was vomiting (n = 25), followed
      by lethargy (12). The median duration of clinical signs prior to presentation was
      93 minutes (range 0-5,040 minutes). Dogs that developed clinical signs ingested a
      significantly higher dose of xylitol than those that were asymptomatic. Thirty
      dogs became hypoglycemic (BG <= 3.3 mmol/L [60 mg/dL]) at some time point during
      their hospitalization. When evaluating all dogs, there was a significant
      difference between the initial and lowest BGs. Thirty dogs had increased alanine
      aminotransferase activity or total serum bilirubin concentration. Dogs with
      increases in alanine aminotransferase activity or total serum bilirubin
      concentration had a significantly lower nadir BG. All dogs survived to discharge
      and 158 were known to be alive at 28 days. The rest were lost to follow up.
      CONCLUSIONS: The prognosis for dogs evaluated by a veterinarian that ingest lower
      doses of xylitol and do not develop liver failure is excellent. Dogs ingesting
      xylitol should be hospitalized and monitored for variations in BG, because BG
      drops in most dogs following presentation. Additional studies are needed in dogs
      ingesting higher doses of xylitol before correlations between dose and the
      development of clinical signs or liver failure can be established. Treatment and
      prognosis for these dogs warrants further investigation.

PMID- 26220655
TI  - Rhabdomyolysis-induced acute kidney injury in a cancer patient exposed to
      denosumab and abiraterone: a case report.
AB  - BACKGROUND: Denosumab and abiraterone were approved by the United States Food and
      Drug Administration in 2011 for the treatment of metastatic castration-resistant
      prostate cancer. Neither denosumab nor abiraterone is known to cause
      rhabdomyolysis. CASE PRESENTATION: A 76-year-old Caucasian man with metastatic
      prostate cancer presented with non-oliguric severe acute kidney injury (AKI) 3
      weeks after receiving simultaneous therapy with denosumab and abiraterone. The
      patient had been on statin therapy for more than 1 year with no recent dose
      adjustments. His physical exam was unremarkable. Blood work on admission revealed
      hyperkalemia, mild metabolic acidosis, hypocalcemia, and elevated creatine kinase
      (CK) at 44,476 IU/L. Kidney biopsy confirmed the diagnosis of rhabdomyolysis
      induced AKI. The patient responded well to intravenous isotonic fluids and
      discontinuation of denosumab, abiraterone, and rosuvastatin, with normalization
      of CK and recovery of kidney function. CONCLUSION: We report the first case of
      biopsy-proven rhabdomyolysis-induced AKI in a cancer patient acutely exposed to
      denosumab and abiraterone. Whether one of these drugs individually, or the
      combination, was the bona fide culprit of muscle breakdown is unknown.
      Nonetheless, our report is hypothesis-generating for further investigations on
      the effect of these drugs on muscle cells.

PMID- 26220656
TI  - Needle age and season influence photosynthetic temperature response and total
      annual carbon uptake in mature Picea mariana trees.
AB  - BACKGROUND AND AIMS: The carbon (C) balance of boreal terrestrial ecosystems is
      sensitive to increasing temperature, but the direction and thresholds of
      responses are uncertain. Annual C uptake in Picea and other evergreen boreal
      conifers is dependent on seasonal- and cohort-specific photosynthetic and
      respiratory temperature response functions, so this study examined the
      physiological significance of maintaining multiple foliar cohorts for Picea
      mariana trees within an ombrotrophic bog ecosystem in Minnesota, USA. METHODS:
      Measurements were taken on multiple cohorts of needles for photosynthetic
      capacity, foliar respiration (Rd) and leaf biochemistry and morphology of mature
      trees from April to October over 4 years. The results were applied to a simple
      model of canopy photosynthesis in order to simulate annual C uptake by cohort age
      under ambient and elevated temperature scenarios. KEY RESULTS: Temperature
      responses of key photosynthetic parameters [i.e. light-saturated rate of CO2
      assimilation (Asat), rate of Rubisco carboxylation (Vcmax) and electron transport
      rate (Jmax)] were dependent on season and generally less responsive in the
      developing current-year (Y0) needles compared with 1-year-old (Y1) or 2-year-old
      (Y2) foliage. Temperature optimums ranged from 18.7 to 23.7, 31.3 to 38.3 and
      28.7 to 36.7  degrees C for Asat, Vcmax and Jmax, respectively. Foliar cohorts
      differed in their morphology and photosynthetic capacity, which resulted in 64 %
      of modelled annual stand C uptake from Y1&2 cohorts (LAI 0.67 m(2 )m(-2)) and
      just 36 % from Y0 cohorts (LAI 0.52 m(2 )m(-2)). Under warmer climate change
      scenarios, the contribution of Y0 cohorts was even less; e.g. 31 % of annual C
      uptake for a modelled 9  degrees C rise in mean summer temperatures. Results
      suggest that net annual C uptake by P. mariana could increase under elevated
      temperature, and become more dependent on older foliar cohorts. CONCLUSIONS:
      Collectively, this study illustrates the physiological and ecological
      significance of different foliar cohorts, and indicates the need for seasonal-
      and cohort-specific model parameterization when estimating C uptake capacity of
      boreal forest ecosystems under ambient or future temperature scenarios.

PMID- 26220657
TI  - Plant defence as a complex and changing phenotype throughout ontogeny.
AB  - BACKGROUND AND AIMS: Ontogenetic changes in anti-herbivore defences are common
      and result from variation in resource availability and herbivore damage
      throughout plant development. However, little is known about the simultaneous
      changes of multiple defences across the entire development of plants, and how
      such changes affect plant damage in the field. The aim of this study was to
      assess if changes in the major types of plant resistance and tolerance can
      explain natural herbivore damage throughout plant ontogeny. METHODS: An
      assessment was made of how six defensive traits, including physical, chemical and
      biotic resistance, simultaneously change across the major transitions of plant
      development, from seedlings to reproductive stages of Turnera velutina growing in
      the greenhouse. In addition, an experiment was performed to assess how plant
      tolerance to artificial damage to leaves changed throughout ontogeny. Finally,
      leaf damage by herbivores was evaluated in a natural population. KEY RESULTS: The
      observed ontogenetic trajectories of all defences were significantly different,
      sometimes showing opposite directions of change. Whereas trichome density, leaf
      toughness, extrafloral nectary abundance and nectar production increased,
      hydrogen cyanide and compensatory responses decreased throughout plant
      development, from seedlings to reproductive plants. Only water content was higher
      at the intermediate juvenile ontogenetic stages. Surveys in a natural population
      over 3 years showed that herbivores consumed more tissue from juvenile plants
      than from younger seedlings or older reproductive plants. This is consistent with
      the fact that juvenile plants were the least defended stage. CONCLUSIONS: The
      results suggest that defensive trajectories are a mixed result of predictions by
      the Optimal Defence Theory and the Growth-Differentiation Balance Hypothesis. The
      study emphasizes the importance of incorporating multiple defences and plant
      ontogeny into further studies for a more comprehensive understanding of plant
      defence evolution.

PMID- 26220658
TI  - Physiology of pepper fruit and the metabolism of antioxidants: chloroplasts,
      mitochondria and peroxisomes.
AB  - BACKGROUND AND AIMS: Pepper (Capsicum annuum) contains high levels of
      antioxidants, such as vitamins A and C and flavonoids. However, information on
      the role of these beneficial compounds in the physiology of pepper fruit remains
      scarce. Recent studies have shown that antioxidants in ripe pepper fruit play a
      key role in responses to temperature changes, and the redox state at the time of
      harvest affects the nutritional value for human consumption. In this paper, the
      role of antioxidant metabolism of pepper fruit during ripening and in the
      response to low temperature is addressed, paying particular attention to
      ascorbate, NADPH and the superoxide dismutase enzymatic system. The participation
      of chloroplasts, mitochondria and peroxisomes in the ripening process is also
      investigated. SCOPE AND RESULTS: Important changes occur at a subcellular level
      during ripening of pepper fruit. Chloroplasts turn into chromoplasts, with
      drastic conversion of their metabolism, and the role of the ascorbate-glutathione
      cycle is essential. In mitochondria from red fruits, higher ascorbate peroxidase
      (APX) and Mn-SOD activities are involved in avoiding the accumulation of reactive
      oxygen species in these organelles during ripening. Peroxisomes, whose
      antioxidant capacity at fruit ripening is substantially affected, display an
      atypical metabolic pattern during this physiological stage. In spite of these
      differences observed in the antioxidative metabolism of mitochondria and
      peroxisomes, proteomic analysis of these organelles, carried out by 2-D
      electrophoresis and MALDI-TOF/TOF and provided here for the first time, reveals
      no changes between the antioxidant metabolism from immature (green) and ripe
      (red) fruits. CONCLUSIONS: Taken together, the results show that investigation of
      molecular and enzymatic antioxidants from cell compartments, especially
      chloroplasts, mitochondria and peroxisomes, is a useful tool to study the
      physiology of pepper fruit, particularly in the context of expanding their shelf
      life after harvest and in maintaining their nutritional value.

PMID- 26220659
TI  - Lack of guilt, guilt, and shame: a multi-informant study on the relations between
      self-conscious emotions and psychopathology in clinically referred children and
      adolescents.
AB  - The present study examined the relationships between dysregulations in self
      conscious emotions and psychopathology in clinically referred children and
      adolescents. For this purpose, parent-, teacher-, and self-report Achenbach
      System of Empirically Based Assessment data of 1000 youth aged 4-18 years was
      analyzed as this instrument not only provides information on the intensity levels
      of lack of guilt, guilt, and shame, but also on the severity of various types of
      psychopathology. The results first of all indicated that dysregulations of self
      conscious emotions were more common in this clinical sample than in the general
      population. Further, a consistent pattern was found with regard to the
      relationships between self-conscious emotions and childhood psychopathology. That
      is, lack of guilt was predominantly associated with oppositional defiant and
      conduct (i.e., externalizing) problems, while guilt and shame were primarily
      linked with affective and anxiety (i.e., internalizing) problems. By and large,
      these findings confirm what has been found in non-clinical youth, and suggest
      that self-conscious emotions play a small but significant role in the
      psychopathology of children and adolescents.

PMID- 26220660
TI  - Single-trial dynamics of motor cortex and their applications to brain-machine
      interfaces.
AB  - Increasing evidence suggests that neural population responses have their own
      internal drive, or dynamics, that describe how the neural population evolves
      through time. An important prediction of neural dynamical models is that
      previously observed neural activity is informative of noisy yet-to-be-observed
      activity on single-trials, and may thus have a denoising effect. To investigate
      this prediction, we built and characterized dynamical models of single-trial
      motor cortical activity. We find these models capture salient dynamical features
      of the neural population and are informative of future neural activity on single
      trials. To assess how neural dynamics may beneficially denoise single-trial
      neural activity, we incorporate neural dynamics into a brain-machine interface
      (BMI). In online experiments, we find that a neural dynamical BMI achieves
      substantially higher performance than its non-dynamical counterpart. These
      results provide evidence that neural dynamics beneficially inform the temporal
      evolution of neural activity on single trials and may directly impact the
      performance of BMIs. 

PMID- 26220662
TI  - Ag/g-C3N4 catalyst with superior catalytic performance for the degradation of
      dyes: a borohydride-generated superoxide radical approach.
AB  - A straightforward approach is developed for fabrication of a visible-light-driven
      Ag/g-C3N4 catalyst. Morphological observation shows that the g-C3N4 sheets are
      decorated with highly dispersed Ag nanoparticles having an average size of 5.6
      nm. The photocatalytic activity measurements demonstrate that the photocatalytic
      degradation rates of methyl orange (MO), methylene blue (MB), and neutral dark
      yellow GL (NDY-GL) over Ag/g-C3N4-4 can reach up to 98.2, 99.3 and 99.6% in the
      presence of borohydride ions (BH4(-)) only with 8, 45, and 16 min visible light
      irradiation, respectively. The significant enhancement in photoactivity of the
      catalyst is mainly attributed to the high dispersity and smaller size of Ag
      nanoparticles, the strong surface plasmon resonance (SPR) effect of metallic Ag
      nanoparticles, the efficient separation of photogenerated charge carriers, the
      additional superoxide radicals (O) generated from the reduction of dissolved
      oxygen in the presence of BH4(-) and the synergistic effect of Ag nanoparticles
      and g-C3N4. 

PMID- 26220661
TI  - Childhood Risk of Parental Absence in Tanzania.
AB  - Although parents might not live with their children for a variety of reasons,
      existing accounts of parental absence often examine one cause in isolation. Using
      detailed longitudinal demographic surveillance data from Rufiji, Tanzania, this
      article examines parental absence due to death, migration, child relocation,
      union dissolution, and union formation from 2001-2011. Employing survival
      analysis, the article quantifies children's risk of absence by cause and
      investigates sociodemographic variation in this risk. Of children born into two
      parent households, 25% experience maternal absence by age 10, and 40% experience
      paternal absence by the same age. Roughly one-quarter of children are born into
      single-mother families with an absent father at birth, and nearly 70% of these
      children experience maternal absence as well by age 10. Despite the emphasis on
      orphanhood in the research and policy communities, parental death is the least
      common cause of absence. Furthermore, although demographic and socioeconomic
      characteristics are strong predictors of absence, variation in these
      relationships across causes underscores the distinctiveness and similarity of
      different reasons for absence.

PMID- 26220663
TI  - Expression analyses of insulin-like peptide 3, RXFP2, LH receptor, and 3beta
      hydroxysteroid dehydrogenase in testes of normal and cryptorchid dogs.
AB  - Insulin-like peptide 3 (INSL3) plays a key role in testicular descent in rodents,
      whereas in domestic animals, many aspects of the roles of INSL3 in reproductive
      organs after puberty are still unknown. This study was undertaken to (1)
      determine the quantitative changes of gene expression of testicular INSL3, its
      receptor (RXFP2), LH receptor, and 3beta-hydroxysteroid dehydrogenase during and
      after puberty in normal male dogs; (2) compare the expressions of these
      substances in normal and cryptorchid dogs; and (3) localize the cells expressing
      INSL3 in normal and retained canine testes. Testes were obtained from small-breed
      normal male dogs (n = 56) and cryptorchid dogs (n = 22). Normal scrotal testes
      from the normal dogs (normal testes), retained testes from both the unilateral
      and bilateral cryptorchid dogs (retained testes), and scrotal testes of the
      unilateral cryptorchid dogs (cryptorchid scrotal testes) were used. We measured
      the concentrations of these testicular messenger RNAs (mRNAs) by quantitative
      real-time reverse transcription polymerase chain reaction, and an enzyme
      immunoassay was used for measuring INSL3 peptide. Immunohistochemistry for INSL3
      peptide was done in paraformaldehyde-fixed frozen testicular tissue. In the
      normal dogs, total amount of INSL3 mRNA per testis tended to decrease (P = 0.05)
      from pubertal (6-12 months) to postpubertal (1-5 years) and decreased (P < 0.01)
      to middle age (5-10 years), but total amount of INSL3 peptide per testis did not
      change among age groups. Concentrations of INSL3 mRNA were higher (P < 0.01) in
      retained testes than those in the normal testes and cryptorchid scrotal testes,
      and similar differences were observed for INSL3 peptide. Reversely, total amounts
      of INSL3 mRNA and peptide per retained testis were lower (P < 0.01) than those
      per normal testis because of smaller weight of retained testes. Concentrations
      and total amount of RXFP2 mRNA in the retained testes were almost nil and lower
      (P < 0.01) than those in the normal testes and in the cryptorchid scrotal testes.
      Total amount of LH receptor mRNA per retained testis was lower (P < 0.01) than
      that per normal testis. The immunohistochemical analysis revealed that INSL3 was
      expressed only in Leydig cells of both the normal and retained canine testes.
      These results suggest that INSL3 in retained testes of cryptorchid dogs is
      substantially expressed per unit-weight basis but may be produced with lower
      amount as a whole testis. Also, this study provides findings that RXFP2 gene is
      expressed scarcely in the retained testes but normally in cryptorchid scrotal
      testes.

PMID- 26220664
TI  - Conditional cancer-specific mortality in T4, N1, or M1 prostate cancer:
      implications for long-term prognosis.
AB  - BACKGROUND: The risk of prostate cancer-specific mortality (PCSM) following a
      diagnosis of prostate cancer may improve after patients have survived a number of
      years after diagnosis. We sought to determine long-term conditional PCSM for
      patients with stage T4, N1, or M1 prostate cancer. METHODS: We identified 66,817
      patients diagnosed with stage IV (T4N0M0, N1M0, or M1) prostate cancer between
      1973 and 2011 using the Surveillance, Epidemiology, and End Results (SEER)
      database. Conditional five-year PCSM was evaluated for each group of patients at
      5, 10, and 15 years of survival according to the Fine & Gray model for competing
      risks after adjusting for tumor grade, age, income level, and marital status.
      Race-stratified analyses were also performed. RESULTS: There were 13,345 patients
      with T4 disease, 12,450 patients with N1 disease, and 41,022 patients with M1
      disease. Median follow-up among survivors in the three groups was 123 months
      (range: 0-382 months), 61 months (range: 0-410 months), and 30 months (range: 0
      370 months), respectively. Conditional PCSM improved in all three groups over
      time. Among patients with T4 disease, 5-year PCSM improved from 13.9% at
      diagnosis to 11.2, 8.1, and 6.5% conditioned on 5, 10, or 15 years of survival,
      respectively (p < 0.001 in all cases). In patients with N1 disease, 5-year PCSM
      increased within the first five years and decreased thereafter, from 18.9% at
      diagnosis to 21.4% (p < 0.001), 17.6% (p = 0.055), and 13.8% (p < 0.001),
      respectively. In patients with metastatic disease, 5-year PCSM improved from
      57.2% at diagnosis to 41.1, 28.8, and 20.8%, respectively (p < 0.001). White race
      was associated with a greater increase in conditional survival compared to non
      white race among those with T4 or N1 disease. CONCLUSIONS: While patients with
      T4, N1, or M1 prostate cancer are never "cured," their odds of cancer-specific
      survival increase substantially after they have survived for 5 or more years.
      Physicians who take care of patients with prostate cancer can use this data to
      guide follow-up decisions and to counsel newly diagnosed patients and survivors
      regarding their long-term prognosis.

PMID- 26220665
TI  - Osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand as
      prognostic factors in rheumatoid arthritis: results from the ESPOIR cohort.
AB  - INTRODUCTION: We previously reported that low ratio of osteoprotegerin (OPG) to
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was associated
      with Disease Activity Score in 28 joints (DAS28) remission at 6 months in
      patients with early rheumatoid arthritis (RA). Here, we aimed to evaluate the
      value of baseline OPG/TRAIL ratio in predicting clinical and radiological
      outcomes in patients with early RA in the ESPOIR cohort. METHODS: OPG and TRAIL
      serum concentrations were assessed in the ESPOIR cohort patients. Patients with
      definite RA were included in this study. Patients were excluded if they had high
      erosion score at baseline (>90(th) percentile) or received biological therapy
      during the first 2 years of follow-up. Data were analyzed by univariate analysis
      and multivariate logistic regression to predict 1-year DAS28 remission and 2-year
      radiographic disease progression. RESULTS: On univariate analysis of 399
      patients, OPG/TRAIL ratio at baseline was significantly lower in patients with
      than without remission at 1 year (p = 0.015). On multivariate logistic regression
      including age, gender, body mass index and DAS28, low OPG/TRAIL ratio was
      independently associated with remission at 1 year (odds ratio 1.68 [95 %
      confidence interval 1.01-2.79]). On univariate analysis, high OPG/TRAIL ratio at
      baseline was associated with rapid progression of erosion at 2 years (p = 0.041),
      and on multivariate logistic regression including age, anti-citrullinated protein
      antibody positivity and C-reactive protein level, OPG/TRAIL ratio independently
      predicted rapid progression of erosion at 2 years. CONCLUSIONS: OPG/TRAIL ratio
      at baseline was an independent predictor of 1-year remission and 2-year rapid
      progression of erosion for patients with early rheumatoid arthritis. Thus,
      OPG/TRAIL ratio could be included in matrix prediction scores to predict rapid
      radiographic progression. Further confirmation in an independent cohort is
      warranted.

PMID- 26220666
TI  - Trend in major neonatal and maternal morbidities accompanying the rise in the
      cesarean delivery rate.
AB  - The aim of the study was to explore a cesarean delivery rate (CDR) beyond which
      major neonatal and maternal morbidities may outweigh the benefits of the
      procedure itself. A retrospective population-based cohort study was conducted at
      a single university teaching hospital between 1993 and 2012. Pregnant women who
      delivered at a gestational age of 23 weeks or more were included. Data including
      delivery mode, brachial plexus injury (BPI), neonatal encephalopathy (NE),
      placenta accreta (PA), blood transfusion (BT), and cesarean hysterectomy (CH) for
      each year were extracted, plotted, and trends analyzed. The Cochran-Armitage
      Trend Test was used to identify trends and correlations. Overall, 83,806
      deliveries took place during this period. CDR increased from 10.9% to 21.7% (p <
      0.001). Significant decreases in the incidence of BPI (p < 0.001) and NE (p =
      0.006) were observed. At CDRs of 13.6% and 20%, there was no further significant
      decrease in the incidence of BPI and NE, respectively. The incidence of BT
      increased significantly (p < 0.001) while the increase in the incidence of PA was
      not significant (p = 0.06) nor the change in the incidence of CH (p = 0.4). A CDR
      of 20% may still confirm additional beneficial effect on major perinatal
      morbidities without a significant increase in the incidence of PA. 

PMID- 26220667
TI  - Estimation of Lattice Enthalpies of Ionic Liquids Supported by Hirshfeld
      Analysis.
AB  - New measurements of vaporization enthalpies for 15 1:1 ionic liquids are
      performed by using a quartz-crystal microbalance. Collection and analysis of 33
      available crystal structures of organic salts, which comprise 13 different
      cations and 12 anions, is performed. Their dissociation lattice enthalpies are
      calculated by a combination of experimental and quantum chemical quantities and
      are divided into the relaxation and Coulomb components to give an insight into
      elusive short-range interaction enthalpies. An empirical equation is developed,
      based on interaction-specific Hirshfeld surfaces and solvation enthalpies, which
      enables the estimation of the lattice enthalpy by using only the crystal
      structure data.

PMID- 26220668
TI  - National health expenditure projections, 2014-24: spending growth faster than
      recent trends.
AB  - Health spending growth in the United States is projected to average 5.8 percent
      for 2014-24, reflecting the Affordable Care Act's coverage expansions, faster
      economic growth, and population aging. Recent historically low growth rates in
      the use of medical goods and services, as well as medical prices, are expected to
      gradually increase. However, in part because of the impact of continued cost
      sharing increases that are anticipated among health plans, the acceleration of
      these growth rates is expected to be modest. The health share of US gross
      domestic product is projected to rise from 17.4 percent in 2013 to 19.6 percent
      in 2024. 

PMID- 26220669
TI  - Exaggerated allometric structures in relation to demographic and ecological
      parameters in Lucanus cervus (Coleoptera: Lucanidae).
AB  - Enlarged weapons and ornamental traits under sexual selection often show a
      positive allometric relationship with the overall body size. The present study
      explores the allometry of mandibles and their supporting structure, the head, in
      males of the European stag beetle, Lucanus cervus. This species shows a
      remarkable dimorphism in mandible shape and size that are used by males in
      intraspecific combats. Stag beetles were captured, measured, weighed, and
      released in the framework of a capture-mark-recapture study. The relationship of
      mandible length (ML) and head width in respect to the overall body size was
      described by a segmented regression model. A linear relationship was detected
      between ML and head width. The scaling relationships for both ML and head width
      identified the same switchpoint, highlighting the advantages of using combined
      results of weapons and their supporting structures in such analysis. These
      results led to a more consistent distinction of males in two morphologies: minor
      and major. The survival probability of individuals was dependent on the
      morphological class and was higher for minor males than for major. Elytron length
      and body mass of the individuals did not show any significant variation during
      the season. Differences in predatory pressure were detected between morphs by the
      collection and analysis of body fragments due to the predatory activity of
      corvids. Morphological differences and shift in demographic and ecological
      parameters between the two classes suggested that selection continues to favor
      intrasexual dimorphism in this species throughout a trade-off mechanism between
      costs and benefits of carrying exaggerated traits.

PMID- 26220670
TI  - Sequence diversity and differential expression of major phenylpropanoid-flavonoid
      biosynthetic genes among three mango varieties.
AB  - BACKGROUND: Mango fruits contain a broad spectrum of phenolic compounds which
      impart potential health benefits; their biosynthesis is catalysed by enzymes in
      the phenylpropanoid-flavonoid (PF) pathway. The aim of this study was to reveal
      the variability in genes involved in the PF pathway in three different mango
      varieties Mangifera indica L., a member of the family Anacardiaceae: Kensington
      Pride (KP), Irwin (IW) and Nam Doc Mai (NDM) and to determine associations with
      gene expression and mango flavonoid profiles. RESULTS: A close evolutionary
      relationship between mango genes and those from the woody species poplar of the
      Salicaceae family (Populus trichocarpa) and grape of the Vitaceae family (Vitis
      vinifera), was revealed through phylogenetic analysis of PF pathway genes. We
      discovered 145 SNPs in total within coding sequences with an average frequency of
      one SNP every 316 bp. Variety IW had the highest SNP frequency (one SNP every 258
      bp) while KP and NDM had similar frequencies (one SNP every 369 bp and 360 bp,
      respectively). The position in the PF pathway appeared to influence the extent of
      genetic diversity of the encoded enzymes. The entry point enzymes phenylalanine
      lyase (PAL), cinnamate 4-mono-oxygenase (C4H) and chalcone synthase (CHS) had low
      levels of SNP diversity in their coding sequences, whereas anthocyanidin
      reductase (ANR) showed the highest SNP frequency followed by flavonoid 3'
      hydroxylase (F3'H). Quantitative PCR revealed characteristic patterns of gene
      expression that differed between mango peel and flesh, and between varieties.
      CONCLUSIONS: The combination of mango expressed sequence tags and availability of
      well-established reference PF biosynthetic genes from other plant species allowed
      the identification of coding sequences of genes that may lead to the formation of
      important flavonoid compounds in mango fruits and facilitated characterisation of
      single nucleotide polymorphisms between varieties. We discovered an association
      between the extent of sequence variation and position in the pathway for up
      stream genes. The high expression of PAL, C4H and CHS genes in mango peel
      compared to flesh is associated with high amounts of total phenolic contents in
      peels, which suggest that these genes have an influence on total flavonoid levels
      in mango fruit peel and flesh. In addition, the particularly high expression
      levels of ANR in KP and NDM peels compared to IW peel and the significant
      accumulation of its product epicatechin gallate (ECG) in those extracts reflects
      the rate-limiting role of ANR on ECG biosynthesis in mango.

PMID- 26220671
TI  - Sulfurifustis variabilis gen. nov., sp. nov., a sulfur oxidizer isolated from a
      lake, and proposal of Acidiferrobacteraceae fam. nov. and Acidiferrobacterales
      ord. nov.
AB  - A novel autotrophic bacterium, strain skN76T, was isolated from sediment of a
      lake in Japan. As sole electron donor to support chemolithoautotrophic growth,
      the strain oxidized thiosulfate, tetrathionate and elemental sulfur. For growth,
      the optimum temperature was 42-45  degrees C and the optimum pH was 6.8-8.2. The
      cells were Gram-stain-negative, catalase-positive and oxidase-positive. The
      strain exhibited changes in morphology depending on growth temperature. Cells
      grown at the optimum temperature were rod-shaped (0.9-3.0 MUm long and 0.3-0.5
      MUm wide), whereas a filamentous form was observed when the strain was cultured
      at the lowest permissive growth temperatures. The G+C content of genomic DNA was
      69 mol%. The major components in the fatty acid profile were C16 : 0, summed
      feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and summed feature 9 (iso-C17 :
      1omega9c and/or 10-methyl C16 : 0). Phylogenetic analysis based on 16S rRNA gene
      sequences indicated that the closest cultivated relative of strain skN76T was
      Acidiferrobacter thiooxydans m-1T, with sequence similarity of 93 %. On the basis
      of its phylogenetic and phenotypic properties, strain skN76T ( = DSM 100313T = 
      NBRC 110942T) is proposed as the type strain of a novel species of a novel genus,
      Sulfurifustis variabilis gen. nov., sp. nov. Novel taxa, Acidiferrobacteraceae
      fam. nov. and Acidiferrobacterales ord. nov., are also proposed to accommodate
      the genera Acidiferrobacter and Sulfurifustis gen. nov.

PMID- 26220673
TI  - Petition calling for health secretary's resignation exceeds 200,000 supporters.

PMID- 26220672
TI  - Validation of the French translation-adaptation of the impact of cancer
      questionnaire version 2 (IOCv2) in a breast cancer survivor population.
AB  - BACKGROUND: The Impact of Cancer version 2 (IOCv2) was designed to assess the
      physical and psychosocial health experience of cancer survivors through its
      positive and negative impacts. Although the IOCv2 is available in English and
      Dutch, it has not yet been validated for use in French-speaking populations. The
      current study was undertaken to provide a comprehensive assessment of the
      reliability and validity of the French language version of the IOCv2 in a sample
      of breast cancer survivors. METHODS: An adapted French version of the IOCv2 as
      well as demographic and medical information were completed by 243 women to
      validate the factor structure divergent/divergent validities and reliability.
      Concurrent validity was assessed by correlating the IOCv2 scales with measures
      from the SF-12, PostTraumatic Growth Inventory and Fear of Cancer Recurrence
      Inventory. RESULTS: The French version of the IOCv2 supports the structure of the
      original version, with four positive impact dimensions and four negative impact
      dimensions. This result was suggested by the good fit of the confirmatory factor
      analysis and the adequate reliability revealed by Cronbach's alpha coefficients
      and other psychometric indices. The concurrent validity analysis revealed
      patterns of association between IOCv2 scale scores and other measures. Unlike the
      original version, a structure with a Positive Impact domain consisting in the
      IOCv2 positive dimensions and a Negative Impact domain consisting in the negative
      ones has not been clearly evidenced in this study. The limited practical use of
      the conditional dimensions Employment Concerns and Relationship Concerns, whether
      the patient is partnered or not, did not make possible to provide evidence of
      validity and reliability of these dimensions as the subsets of sample to work
      with were not large enough. The scores of these conditional dimensions have to be
      used with full knowledge of the facts of this limitation of the study.
      CONCLUSIONS: Integrating IOCv2 into studies will contribute to evaluate the
      psychosocial health experience of the growing population of cancer survivors,
      enabling better understanding of the multi-dimensional impact of cancer.

PMID- 26220674
TI  - Diffusion in Li2O studied by non-equilibrium molecular dynamics for 873 < T/K <
      1603.
AB  - The use of non-equilibrium molecular dynamics facilitates the calculation of the
      cation diffusion constant of Li2O at temperatures too low to be accessible by
      other methods. Excellent agreement with experimental diffusion coefficients has
      been obtained over the temperature range 873 < T/K < 1603. Diffusion below 1200 K
      was shown to be dominated by a concerted nearest-neighbour hopping process,
      whereas in the high-temperature superionic region an additional mechanism
      involving a six-coordinate interstitial cation site in the anti-fluorite
      structure becomes increasingly dominant. Our model thus accounts for the
      transition from the superionic regime to the non-superionic regime. 

PMID- 26220675
TI  - Modified Spiral Intestinal Lengthening and Tailoring for Short Bowel Syndrome.
AB  - BACKGROUND: The spiral intestinal lengthening and tailoring (SILT) procedure is a
      new surgical technique for autologous intestinal reconstruction in patients with
      short bowel syndrome. The aim of this work is to present a first description of a
      modified SILT technique by which the mucosal layer is left intact to possibly
      reduce the severe postoperative complications of intestinal leakage and abdominal
      abscess formation. MATERIALS AND METHODS: The modified SILT technique was
      performed on a 10-cm-long intestinal segment in 2 pigs to determine the technical
      feasibility. Thereafter, the short-term clinical feasibility was monitored
      clinically in 2 dogs by gastrointestinal X-ray series at postoperative day 4 and
      by relaparotomy postoperative day 10. RESULTS: It was technically feasible to
      lengthen the intestinal segment from 10 cm to 20 cm and tailoring it from 3 cm to
      1.7 cm in diameter, while leaving the intestinal mucosal layer intact. The
      postoperative course was uneventful for both dogs. The gastrointestinal X-ray
      series showed an inconspicuous intestinal transit time without any signs of
      stricture, perforation, or leakage. In the relaparotomy, the initially achieved
      lengthening and tailoring extents were preserved and the operated intestinal
      segment was well perfused with no early signs of necrosis, stenosis, or leakage.
      CONCLUSIONS: Leaving the mucosal layer intact during SILT is technically and
      clinically feasible in the short term in a large animal model. Further studies
      are needed to fully assess the impact of this technical modification on the long
      term outcome of larger series.

PMID- 26220676
TI  - Evaluating Robotic Surgical Skills Performance Under Distractive Environment
      Using Objective and Subjective Measures.
AB  - BACKGROUND: Distractions are recognized as a significant factor affecting
      performance in safety critical domains. Although operating rooms are generally
      full of distractions, the effect of distractions on robot-assisted surgical (RAS)
      performance is unclear. Our aim was to investigate the effect of distractions on
      RAS performance using both objective and subjective measures. METHODS: Fifteen
      participants performed a knot-tying task using the da Vinci Surgical System and
      were exposed to 3 distractions: (1) passive distraction entailed listening to
      noise with a constant heart rate, (2) active distraction included listening to
      noise and acknowledging a change of random heart rate from 60 to 120 bpm, and (3)
      interactive distraction consisted of answering math questions. The objective
      kinematics of the surgical instrument tips were used to evaluate performance.
      Electromyography (EMG) of the forearm and hand muscles of the participants were
      collected. The median EMG frequency (EMG(fmed)) and the EMG envelope (EMG(env))
      were analyzed. NASA Task Load Index and Fundamentals of Laparoscopic Surgery
      score were used to evaluate the subjective performance. One-way repeated analysis
      of variance was applied to examine the effects of distraction on skills
      performance. Spearman's correlations were conducted to compare objective and
      subjective measures. RESULTS: Significant distraction effect was found for all
      objective kinematics measures (P < .05). There were significant distraction
      effects for EMG measures (EMG(env), P < .004; EMG(fmed), P = .031). Significant
      distraction effects were also found for subjective measurements. CONCLUSIONS:
      Distraction impairs surgical skills performance and increases muscle work.
      Understanding how the surgeons cope with distractions is important in developing
      surgical education.

PMID- 26220678
TI  - Deployment guidelines for diplomats: current policy and practice.
AB  - BACKGROUND: Diplomatic organizations routinely send staff to high-threat postings
      (HTPs) and consequentially have moral and legal obligations to protect their
      health as far as is reasonably practicable. AIMS: To carry out an international
      survey of diplomatic organizations that send personnel to HTPs to establish how
      they deal practically with their obligations to protect the mental health of
      their staff. METHODS: An online anonymous survey about their organizations'
      policies relating to HTPs completed by international diplomatic organizations.
      RESULTS: Fourteen of 30 organizations approached completed the questionnaire,
      with a response rate of 47%. Deployment length varied: no minimum (15%), a
      minimum of 2 years (39%) and a maximum of 2 (31%), 3 (15%) or 4 years (31%); one
      organization did not state any maximum. HTP and low-threat postings had the same
      policies in 46% of organizations. Additional care and support (66%), additional
      preparation (50%), enhanced leave (33%) and additional physical and mental health
      assessments were informally adopted to address psychosocial risks of deployment
      to HTPs. CONCLUSIONS: There was little consensus on policies and practice for HTP
      deployment. We suggest that formal, consistently written guidelines, based on
      available quality evidence, and associated training and quality assurance should
      be formulated to make international practice more consistent and equitable.

PMID- 26220677
TI  - What are the factors associated with depressive symptoms among orphans and
      vulnerable children in Cambodia?
AB  - BACKGROUND: Compared to general children, orphans and vulnerable children (OVC)
      are more exposed to negative outcomes in life such as abuse and neglect.
      Consequently, OVC are more susceptible to depression. This paper investigated
      factors associated with depressive symptoms among OVC in Cambodia. METHODS: In
      this cross-sectional study, data of 606 OVC from the Sustainable Action against
      HIV and AIDS in Communities (SAHACOM) project were analyzed. The data were
      collected from five provinces and analyzed separately for boys and girls.
      Multiple linear regression analysis was used to identify factors independently
      associated with levels of depressive symptoms. RESULTS: Both boys and girls who
      reported having been too sick making them unable to attend school or go to work
      in the past six months (boys: B = 3.5; 95 % CI = 0.7, 6.2; girls: B = 5.7; 95 %
      CI = 2.9, 8.5) and who had witnessed violence in the family (boys: B = 5.6; 95 %
      CI = 1.6, 9.6; girls: B = 5.8; 95 % CI = 1.7, 9.9) had a higher level of
      depressive symptoms. Girls who were older (B = 8.5; 95 % CI = 3.0, 14.0), who did
      not have enough food in the past six months (B = -8.7; 95 % CI = -13.7, -3.7) and
      whose parents were separated, divorced or dead (B = 3.9; 95 % CI = 0.5, 7.2) had
      a higher level of depressive symptoms. Higher level of school attachment was
      negatively associated with depressive symptoms in both genders (boys: B = -1.4;
      95 % CI = -2.0, -0.9; girls: B = -1.4; 95 % CI = -2.0,-0.9). CONCLUSIONS: Factors
      such as physical health and exposure to violence may affect mental health of OVC
      in Cambodia. As health is of utmost importance, better healthcare services should
      be made easily accessible for OVC. Schools have the potential to act as a buffer
      against depressive symptoms. Therefore, efforts should be made to keep OVC in
      school and to improve the roles of school in Cambodia.

PMID- 26220679
TI  - Health risk factors associated with presenteeism in a Chinese enterprise.
AB  - BACKGROUND: Chronic health problems are prevalent in China and may lead to loss
      of work productivity through presenteeism. AIMS: To investigate the prevalence of
      potential risk factors for presenteeism in Chinese workers and the strength of
      their association with reported presenteeism. METHODS: A cross-sectional survey
      of employees in a Chinese petrochemical corporation included a medical
      examination report and questionnaire data on demographic characteristics,
      potential risk factors for presenteeism and presenteeism evaluation. Data were
      analysed using Pearson's chi-square tests, t-tests and logistic regression
      modelling. RESULTS: There were 1506 responses available for analysis; response
      rate 92%. The prevalence of presenteeism was 15%. Univariate analysis indicated a
      significantly higher prevalence of presenteeism in employees who were male, age
      <=35 years, single, divorced or widowed and overweight or obese. Higher
      presenteeism was found in participants with high blood pressure,
      hypertriglyceridemia, hypercholesterolemia, insufficient physical activity,
      cigarette smoking, alcohol use, insufficient cereal intake, life dissatisfaction
      and job dissatisfaction. The prevalence of presenteeism was significantly
      associated with the number of potential risk factors. Logistic regression
      disclosed six independent risk factors associated with presenteeism:
      hypercholesterolemia, high blood pressure, insufficient physical activity,
      alcohol drinking, insufficient cereal intake and life dissatisfaction.
      CONCLUSIONS: Chronic conditions, health risk factors and presenteeism were
      prevalent in employees of a Chinese petrochemical corporation. Risk factors for
      other health conditions were associated with presenteeism. Health management
      programmes should be implemented to reduce risk factors and promote the health of
      employees in an effort to reduce presenteeism.

PMID- 26220680
TI  - Melatonin treatment in spring and reproductive recovery in sheep with different
      body condition score and age.
AB  - With the aim to evaluate the effect of melatonin treatment on the advanced
      reproductive recovery in sheep with different body condition score (BCS) and age,
      800 ewes were selected from two farms. These ewes (3-6 years old, multiparous and
      with BCS 2.5-4.0) were subdivided into two Groups (200 M and 200 C), balanced on
      their BCS and age. On 20 March, Group M was treated with one melatonin implant
      (18 mg). Group C was untreated. Males were introduced to the groups 35 days after
      treatment. Gestation was diagnosed between day 45 and 90 after mating by
      transabdominal ultrasonography. From day 150 to 190 after rams introduction,
      lambing date and newborns' number were recorded. The average time in days between
      male introduction and lambing resulted shorter in treated than in control ewes
      (166.4 +/- 0.48 vs. 172.5 +/- 0.50) (P < 0.05). At day 160 and 170 from ram
      introduction the fertility rate was higher in Group M than in C (P < 0.05). The
      overall fertility at day 190 from rams introduction showed no differences between
      Group M and C (337 and 339, respectively). At day 170 from male introduction the
      number of the 5-6 years-old lambed ewes were 2-fold higher than the youngers (P <
      0.05). The animals with a BCS 3.5-4.0 had a faster response to male effect, and a
      shorter mean distance in days from rams introduction to lambing, compared to
      those scored 2.5-3.0 (166.1 +/- 0.48 vs. 174.8 +/- 0.51) (P < 0.05). We concluded
      that the ewes with BCS 3.5-4.0 and aged 5-6 years showed a better response to
      melatonin treatment in spring.

PMID- 26220682
TI  - SpirPro: A Spirulina proteome database and web-based tools for the analysis of
      protein-protein interactions at the metabolic level in Spirulina (Arthrospira)
      platensis C1.
AB  - BACKGROUND: Spirulina (Arthrospira) platensis is the only cyanobacterium that in
      addition to being studied at the molecular level and subjected to gene
      manipulation, can also be mass cultivated in outdoor ponds for commercial use as
      a food supplement. Thus, encountering environmental changes, including
      temperature stresses, is common during the mass production of Spirulina. The use
      of cyanobacteria as an experimental platform, especially for photosynthetic gene
      manipulation in plants and bacteria, is becoming increasingly important.
      Understanding the mechanisms and protein-protein interaction networks that
      underlie low- and high-temperature responses is relevant to Spirulina mass
      production. To accomplish this goal, high-throughput techniques such as OMICs
      analyses are used. Thus, large datasets must be collected, managed and subjected
      to information extraction. Therefore, databases including (i) proteomic analysis
      and protein-protein interaction (PPI) data and (ii) domain/motif visualization
      tools are required for potential use in temperature response models for plant
      chloroplasts and photosynthetic bacteria. DESCRIPTIONS: A web-based repository
      was developed including an embedded database, SpirPro, and tools for network
      visualization. Proteome data were analyzed integrated with protein-protein
      interactions and/or metabolic pathways from KEGG. The repository provides various
      information, ranging from raw data (2D-gel images) to associated results, such as
      data from interaction and/or pathway analyses. This integration allows in silico
      analyses of protein-protein interactions affected at the metabolic level and,
      particularly, analyses of interactions between and within the affected metabolic
      pathways under temperature stresses for comparative proteomic analysis. The
      developed tool, which is coded in HTML with CSS/JavaScript and depicted in
      Scalable Vector Graphics (SVG), is designed for interactive analysis and
      exploration of the constructed network. SpirPro is publicly available on the web
      at http://spirpro.sbi.kmutt.ac.th . CONCLUSIONS: SpirPro is an analysis platform
      containing an integrated proteome and PPI database that provides the most
      comprehensive data on this cyanobacterium at the systematic level. As an
      integrated database, SpirPro can be applied in various analyses, such as
      temperature stress response networking analysis in cyanobacterial models and
      interacting domain-domain analysis between proteins of interest.

PMID- 26220681
TI  - Effect of periconceptional nutrition on the growth, behaviour and survival of the
      neonatal lamb.
AB  - Periconceptional nutrition (PCN) can influence foetal hypothalamo-pituitary
      adrenal (HPA) axis function and alter cortisol secretion with possible
      consequences for maturation and growth of major organs, gestation length and
      behaviour. We examined effects of PCN on phenotype and survival of the neonatal
      lamb in 466 Merino ewes allocated to treatments providing 70%, 100% and 150%
      respectively, of maintenance requirements for 17 days prior and 6 days after
      insemination. Gestation length and birth weight for lambs in PCN treatment groups
      was similar (P > 0.05) but low PCN decreased the size of the neonate (crown-rump
      length and metacarpal length P < 0.05). A subset of lambs euthanased at 5 days of
      age further showed that low PCN decreased the amount of peri-renal fat (P < 0.05)
      and increased liver mass (P < 0.05) while high PCN increased neck thymus and
      ovary mass (P < 0.05). Neonatal lambs from low PCN ewes returned faster to their
      mothers after release (P < 0.05) and contacted the udder in the shortest time (P
      < 0.05). Significant interactions between PCN treatment and sex (P < 0.05) and
      between PCN treatment and ewe age (P < 0.05) were also observed for time lambs
      took to follow the ewe. Survival of lambs was similar but potential differences
      may have been masked by favourable weather conditions. In conclusion, this study
      provides evidence of significant changes in lamb growth and development dependent
      on PCN and, for the first time, links these changes with significant changes in
      behaviour of the neonate. The impact of these effects on lamb survival and
      potential reproductive capacity of female offspring remains to be determined.

PMID- 26220683
TI  - Robotic surgery of the pancreas: The current state of the art.
AB  - Pancreatic surgery is one of the most technically challenging and complex types
      of surgery. Most pancreatic surgery is performed with the open technique, yet
      minimally invasive surgery has become the standard of care for many other intra
      abdominal operations. The unique qualities of the robotic platform have made this
      approach to pancreatic surgery safe and feasible with at least equivalent if not
      better results than the open platform in terms of surgical and oncological
      outcomes.

PMID- 26220684
TI  - Common polygenic variation contributes to risk of migraine in the Norfolk Island
      population.
AB  - Migraine has been defined as a common disabling primary headache disorder.
      Epidemiology studies have provided with the undeniable evidence of genetic
      components as active players in the development of the disease under a polygenic
      model in which multiple risk alleles exert modest individual effects. Our
      objective was to test the contribution of a polygenic effect to migraine risk in
      the Norfolk Island population using a panel of SNPs reported to be disease
      associated in published migraine GWAS. We also investigated whether individual
      SNPs were associated with gene expression levels measured in whole blood.
      Polygenic scores were calculated in a total of 285 related individuals (74 cases,
      211 controls) from the Norfolk Island using 51 SNPs previously reported to be
      associated with migraine in published GWAS. The association between polygenic
      score and migraine case-control status was tested using logistic regression.
      Results indicate that a migraine polygenic risk score was associated with
      migraine case-control status in this population (P = 0.016). This supports the
      hypothesis that multiple SNPs with weak effects collectively contribute to
      migraine risk in this population. Amongst the SNPs included in the polygenic
      model, four were associated with the expression of the USMG5 gene, including
      rs171251 (P = 0.012). Results from this study provide evidence for a polygenic
      contribution to migraine risk in an isolated population and highlight specific
      SNPs that regulate the expression of USMG5, a gene critical for mitochondrial
      function.

PMID- 26220685
TI  - 2D-DIGE and MALDI TOF/TOF MS analysis reveal that small GTPase signaling pathways
      may play an important role in cadmium-induced colon cell malignant
      transformation.
AB  - Cadmium is a toxic heavy metal present in the environment and in industrial
      materials. Cadmium has demonstrated carcinogenic activity that induces cell
      transformation, but how this occurs is unclear. We used 2D-DIGE and MALDI TOF/TOF
      MS combined with bioinformatics and immunoblotting to investigate the molecular
      mechanism of cadmium transformation. We found that small GTPases were critical
      for transformation. Additionally, proteins involved in mitochondrial
      transcription, DNA repair, and translation also had altered expression patterns
      in cadmium treated cells. Collectively, our results suggest that activation of
      small GTPases contributes to cadmium-induced transformation of colon cells. 

PMID- 26220686
TI  - Gene-arsenic interaction in longitudinal changes of blood pressure: Findings from
      the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh.
AB  - Cardiovascular disease (CVD) is the leading cause of morbidity and mortality
      worldwide and mounting evidence indicates that toxicant exposures can profoundly
      impact on CVD risk. Epidemiologic studies have suggested that arsenic (As)
      exposure is positively related to increases in blood pressure (BP), a primary CVD
      risk factor. However, evidence of whether genetic susceptibility can modify the
      association between As and BP is lacking. In this study, we used mixed effect
      models adjusted for potential confounders to examine the interaction between As
      exposure from well water and potential genetic modifiers on longitudinal change
      in BP over approximately 7years of follow-up in 1137 subjects selected from the
      Health Effects of Arsenic Longitudinal Study (HEALS) cohort in Bangladesh.
      Genotyping was conducted for 235 SNPs in 18 genes related to As metabolism,
      oxidative stress and endothelial function. We observed interactions between 44
      SNPs with well water As for one or more BP outcome measures (systolic, diastolic,
      or pulse pressure (PP)) over the course of follow-up. The interaction between
      CYBA rs3794624 and well water As on annual PP remained statistically significant
      after correction for multiple comparisons (FDR-adjusted p for interaction=0.05).
      Among individuals with the rs3794624 variant genotype, well water As was
      associated with a 2.23mmHg (95% CI: 1.14-3.32) greater annual increase in PP,
      while among those with the wild type, well water As was associated with a
      0.13mmHg (95% CI: 0.02-0.23) greater annual increase in PP. Our results suggest
      that genetic variability may contribute to As-associated increases in BP over
      time.

PMID- 26220688
TI  - Improving heterologous protein secretion at aerobic conditions by activating
      hypoxia-induced genes in Saccharomyces cerevisiae.
AB  - Oxygen is important for normal aerobic metabolism, as well as for protein
      production where it is needed for oxidative protein folding. However, several
      studies have reported that anaerobic conditions seem to be more favorable in
      terms of recombinant protein production. We were interested in increasing
      recombinant protein production under aerobic conditions so we focused on Rox1p
      regulation. Rox1p is a transcriptional regulator, which in oxidative conditions
      represses genes induced in hypoxia. We deleted ROX1 and studied the effects on
      the production of recombinant proteins in Saccharomyces cerevisiae. Intriguingly,
      we found a 100% increase in the recombinant fungal alpha-amylase yield, as well
      as productivity. Varied levels of improvements were also observed for the
      productions of the human insulin precursor and the yeast endogenous enzyme
      invertase. Based on the genome-wide transcriptional response, we specifically
      focused on the effect of UPC2 upregulation on protein production and suggested a
      possible mechanistic explanation. 

PMID- 26220687
TI  - Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF
      kappaB signalings in colorectal cancer cells.
AB  - Arsenic is a known carcinogen to humans, and chronic exposure to environmental
      arsenic is a worldwide health concern. As a dietary factor, ethanol carries a
      well-established risk for malignancies, but the effects of co-exposure to arsenic
      and ethanol on tumor development are not well understood. In the present study,
      we hypothesized that ethanol would enhance the function of an environmental
      carcinogen such as arsenic through increase in COX-2 expression. Our in vitro
      results show that ethanol enhanced arsenic-induced COX-2 expression. We also show
      that the increased COX-2 expression associates with intracellular ROS generation,
      up-regulated AKT signaling, with activation of both NFAT and NF-kappaB pathways.
      We demonstrate that antioxidant enzymes have an inhibitory effect on
      arsenic/ethanol-induced COX-2 expression, indicating that the responsive
      signaling pathways from co-exposure to arsenic and ethanol relate to ROS
      generation. In vivo results also show that co-exposure to arsenic and ethanol
      increased COX-2 expression in mice. We conclude that ethanol enhances arsenic
      induced COX-2 expression in colorectal cancer cells via both the NFAT and NF
      kappaB pathways. These results imply that, as a common dietary factor, ethanol
      ingestion may be a compounding risk factor for arsenic-induced
      carcinogenesis/cancer development. 

PMID- 26220689
TI  - The nursing contribution to nutritional care in cancer cachexia.
AB  - Cancer cachexia is a complex syndrome. Its defining feature is involuntary weight
      loss, which arises, in part, because of muscle atrophy and is accompanied by
      functional decline. International expert consensus recommends that nutritional
      support and counselling is a component of multimodal therapy for cancer cachexia,
      as poor nutritional intake can contribute to progression of the syndrome. The
      present paper focuses on what is presently known about the nursing contribution
      to nutritional care in cancer cachexia. There is potential for nurses to play an
      important role. However, obstacles to this include lack of a robust evidence base
      to support their nutritional care practices and unmet need for education about
      nutrition in cancer. The nursing role's boundaries and the outcomes of nurse
      delivered nutritional care in cancer cachexia are both uncertain and should be
      investigated. 

PMID- 26220690
TI  - PET imaging of TSPO in a rat model of local neuroinflammation induced by
      intracerebral injection of lipopolysaccharide.
AB  - OBJECTIVE: The goal of this study was to measure functional and structural
      aspects of local neuroinflammation induced by intracerebral injection of
      lipopolysaccharide (LPS) in rats using TSPO microPET imaging with [(18)F]DPA-714,
      magnetic resonance imaging (MRI), in vitro autoradiography and
      immunohistochemistry (IHC) in order to characterize a small animal model for
      screening of new PET tracers targeting neuroinflammation. METHODS: Rats were
      injected stereotactically with LPS (50 MUg) in the right striatum and with saline
      in the left striatum. [(18)F]DPA-714 microPET, MRI, in vitro autoradiography and
      IHC studies were performed at different time points after LPS injection for 1
      month. RESULTS: Analysis of the microPET data demonstrated high uptake of the
      tracer in the LPS injected site with an affected-to-non-affected side-binding
      potential ratio (BPright-to-left) of 3.0 at 3 days after LPS injection. This BP
      ratio decreased gradually over time to 0.9 at 30 days after LPS injection. In
      vitro autoradiography ([(18)F]DPA-714) and IHC (CD68, GFAP and TSPO) confirmed
      local neuroinflammation in this model. Dynamic contrast enhanced (DCE) MRI
      demonstrated BBB breakdown near the LPS injection site at day 1, which gradually
      resolved over time and was absent at 1 month after LPS injection. CONCLUSION: The
      LPS model is useful for first screening of newly developed tracers because of the
      easy design and the robust, unilateral inflammatory reaction allowing the use of
      the contralateral region as control. Additionally, this model can be used to test
      and follow up the benefits of anti-inflammatory therapies by non-invasive
      imaging.

PMID- 26220692
TI  - Selective Alkylation of C-Rich Bulge Motifs in Nucleic Acids by Quinone Methide
      Derivatives.
AB  - A quinone methide precursor featuring a bis-cyclen anchoring moiety has been
      synthesized and its capacity to alkylate oligonucleotide targets quantified in
      the presence and absence of divalent metal ions (Zn(2+) , Ni(2+) and Cd(2+) ).
      The oligonucleotides were designed for testing the sequence and secondary
      structure specificity of the reaction. Gel electrophoretic analysis revealed
      predominant alkylation of C-rich bulges, regardless of the presence of divalent
      metal ions or even the bis-cyclen anchor. This C-selectivity appears to be an
      intrinsic property of the quinone methide electrophile as reflected by its
      reaction with an equimolar mixture of the 2'-deoxynucleosides. Only dA-N1 and dC
      N3 alkylation products were detected initially and only the dC adduct persisted
      for detection under conditions of the gel electrophoretic analysis. 

PMID- 26220691
TI  - Mobile Phone-Connected Wearable Motion Sensors to Assess Postoperative
      Mobilization.
AB  - BACKGROUND: Early mobilization after surgery reduces the incidence of a wide
      range of complications. Wearable motion sensors measure movements over time and
      transmit this data wirelessly, which has the potential to monitor patient
      recovery and encourages patients to engage in their own rehabilitation.
      OBJECTIVE: We sought to determine the ability of off-the-shelf activity sensors
      to remotely monitor patient postoperative mobility. METHODS: Consecutive subjects
      were recruited under the Department of Neurosurgery at Columbia University.
      Patients were enrolled during physical therapy sessions. The total number of
      steps counted by the two blinded researchers was compared to the steps recorded
      on four activity sensors positioned at different body locations. RESULTS: A total
      of 148 motion data points were generated. The start time, end time, and duration
      of each walking session were accurately recorded by the devices and were remotely
      available for the researchers to analyze. The sensor accuracy was significantly
      greater when placed over the ankles than over the hips (P<.001). Our multivariate
      analysis showed that step length was an independent predictor of sensor accuracy.
      On linear regression, there was a modest positive correlation between increasing
      step length and increased ankle sensor accuracy (r=.640, r(2)=.397) that reached
      statistical significance on the multivariate model (P=.03). Increased gait speed
      also correlated with increased ankle sensor accuracy, although less strongly
      (r=.444, r(2)=.197). We did not note an effect of unilateral weakness on the
      accuracy of left- versus right-sided sensors. Accuracy was also affected by
      several specific measures of a patient's level of physical assistance, for which
      we generated a model to mathematically adjust for systematic underestimation as
      well as disease severity. CONCLUSIONS: We provide one of the first assessments of
      the accuracy and utility of widely available and wirelessly connected activity
      sensors in a postoperative patient population. Our results show that activity
      sensors are able to provide invaluable information about a patient's mobility
      status and can transmit this data wirelessly, although there is a systematic
      underestimation bias in more debilitated patients.

PMID- 26220693
TI  - Palladium-catalyzed direct ortho-ethoxycarbonylation of azobenzenes and
      azoxybenzenes with diethyl azodicarboxylate.
AB  - A palladium-catalyzed direct ortho-ethoxycarbonylation of azobenzenes and
      azoxybenzenes with diethyl azodicarboxylate (DEAD) was developed. In the presence
      of Cu(OAc)2 or (NH4)2S2O8 as the oxidant, this protocol allowed using both
      electron-deficient and electron-rich azobenzenes and azoxybenzenes to produce the
      corresponding products in moderate to good yields. 

PMID- 26220695
TI  - Comparison of Left Atrial and Biatrial Maze Procedure in the Treatment of Atrial
      Fibrillation: A Meta-Analysis of Clinical Studies.
AB  - Background The outcomes of atrial fibrillation (AF) between biatrial maze (BAM)
      and left atrial maze (LAM) are still controversial. The purpose of this study was
      to compare the clinical and rhythm outcomes between BAM and LAM in patients with
      AF. Methods Electronic databases and article references were systematically
      searched (1990-2014) to access relevant studies. Odds ratio (OR) and weight mean
      difference (WMD) with 95% confidence interval (CI) were reported. Results
      Fourteen studies with 2,075 patients were finally involved in the present meta
      analysis. The rate of restored sinus rhythm (SR) was similar in BAM and LAM
      groups (OR: 1.25, 95% CI: 0.91-1.72, p = 0.163). BAM reduced the prevalence of
      atrial flutter during follow-up (OR: 0.12, 95% CI: 0.01-0.96, p = 0.046).
      Compared with BAM, LAM shorten aortic cross-clamping time (WMD = 9.05 minutes,
      95% CI: 1.28-16.82, p = 0.023) and cardiopulmonary bypass time (WMD = 20.21
      minutes, 95% CI: 7.40-33.03, p = 0.002). No significant difference was found
      between groups in the risk of death (OR: 1.22, 95% CI: 0.70-2.14, p = 0.233),
      cerebrovascular events (OR: 1.44, 95% CI: 0.51-4.06, p = 0.493), and reoperation
      for bleeding (OR: 1.34, 95% CI: 0.70-2.55, p = 0.374). However, the risk for
      implantation of permanent pacemaker was significantly higher in BAM group (OR:
      2.60, 95% CI: 1.09-6.20, p = 0.031). Conclusion No significant difference was
      found between BAM and LAM in the rate of restored SR, the risk of death,
      cerebrovascular events, and reoperation for bleeding. BAM is superior to LAM in
      reducing the prevalence of atrial flutter during follow-up, but LAM shortens the
      aortic cross-clamping time and cardiopulmonary bypass time, and decreases the
      risk of permanent pacemaker implantation.

PMID- 26220694
TI  - A putative 6-transmembrane nitrate transporter OsNRT1.1b plays a key role in rice
      under low nitrogen.
AB  - OsNRT1.1a is a low-affinity nitrate (NO3 (-) ) transporter gene. In this study,
      another mRNA splicing product, OsNRT1.1b, putatively encoding a protein with six
      transmembrane domains, was identified based on the rice genomic database and
      bioinformatics analysis. OsNRT1.1a/OsNRT1.1b expression in Xenopus oocytes showed
      OsNRT1.1a-expressing oocytes accumulated (15) N levels to about half as compared
      to OsNRT1.1b-expressing oocytes. The electrophysiological recording of OsNRT1.1b
      expressing oocytes treated with 0.25 mM NO3 (-) confirmed (15) N accumulation
      data. More functional assays were performed to examine the function of OsNRT1.1b
      in rice. The expression of both OsNRT1.1a and OsNRT1.1b was abundant in roots and
      downregulated by nitrogen (N) deficiency. The shoot biomass of transgenic rice
      plants with OsNRT1.1a or OsNRT1.1b overexpression increased under various N
      supplies under hydroponic conditions compared to wild-type (WT). The OsNRT1.1a
      overexpression lines showed increased plant N accumulation compared to the WT in
      1.25 mM NH4 NO3 and 2.5 mM NO3 (-) or NH4 (+) treatments, but not in 0.125 mM NH4
      NO3 . However, OsNRT1.1b overexpression lines increased total N accumulation in
      all N treatments, including 0.125 mM NH4 NO3 , suggesting that under low N
      condition, OsNRT1.1b would accumulate more N in plants and improve rice growth,
      but also that OsNRT1.1a had no such function in rice plants. 

PMID- 26220696
TI  - Bronchopulmonary Carcinoids causing Cushing Syndrome: Results from a Multicentric
      Study Suggesting a More Aggressive Behavior.
AB  - OBJECTIVE: Cushing syndrome (CS) caused by bronchopulmonary carcinoids (BCs) is a
      very rare entity. The aim of this study was to revisit the features of a
      multicenter clinical series to identify significant prognostic factors. METHODS:
      From January 2002 to December 2013, the clinical and pathological data of 23
      patients (treated in five different institutions) were retrospectively reviewed.
      Survival analysis was performed to explore the relative weight of potential
      prognostic factors. RESULTS: Median age and male/female ratio were 48 years and
      14/9, respectively. Most (> 80%) of the patients presented with CS-related
      symptoms at diagnosis. Tumor location was peripheral in 13 patients (57%) and
      central in 10 (43%). All patients but two (treated with chemotherapy) underwent
      surgical resection with curative intent. Definitive cyto/histology was indicative
      of typical carcinoid (TC) in 16 cases (70%) and atypical carcinoid (AC) in 7
      cases (30%). A complete remission of CS was obtained in 16 cases (70%). Lymph
      nodal involvement was detected in 11 cases (48%), with N2 disease occurring in 7
      (~ 30% of all cases). Four patients (22%) experienced a relapse of the disease
      after radical surgery. Overall 5-year survival (long-term survival, LTS) was 60%,
      better in TCs when compared with AC (LTS: 66 v s. 48%, p = 0.28). Log-rank
      analysis identified ECOG performance status, cTNM and cN staging, pTNM and pN
      staging, persistence of CS and relapses (local p = 0.006; distant p = 0.001) as
      significant prognostic factors in this cohort of patients. CONCLUSION: BCs
      causing CS are characterized by a high rate of lymph-nodal involvement, a
      suboptimal prognosis (5-year survival = 60%, 66% in TCs) and a remarkable risk of
      relapse even after radical resection. Advanced stage, lymph-nodal involvement and
      the persisting of the CS after treatment correlate with a poor prognosis.

PMID- 26220697
TI  - Quality Assessment of Video Mediastinoscopy Performed for Staging in Non-Small
      Cell Lung Cancer.
AB  - Background Mediastinoscopy is considered to be the gold standard for mediastinal
      staging for patients with non-small cell lung cancer (NSCLC). The diagnostic
      value depends on how this procedure is performed, which has resulted in drafting
      a guideline by the European Society of Thoracic Surgery (ESTS). Biopsy of at
      least stations 4R, 4L, 7, and if present stations 2R and 2L, is recommended. The
      objective of this study is to assess the quality of the mediastinoscopies
      performed in our hospital for NSCLC. Methods Medical records of 102 consecutive
      patients with suspected or proven NSCLC and a performed cervical mediastinoscopy
      between January 2009 and November 2014 were analyzed in a retrospective cohort
      study. The number of biopsied stations and complications has been prospectively
      documented, together with their clinical data. Results Cervical mediastinoscopy
      was performed in 102 patients and in 51 (50%) patients biopsy was taken of
      stations 4R, 4L, and 7. N2/N3 disease emerged more significantly (p < 0.05) if
      biopsies were taken of at least the paratracheal stations 4R/4L and the
      subcarinal region. The incidence of major complications was 3.9%. Conclusion In
      our clinic, 50% of the mediastinoscopies performed are executed following the
      ESTS guidelines. Our results subscribe the need to biopsy at least the
      paratracheal stations 4L/4R and the subcarinal region to obtain a reliable
      assessment of the mediastinum. 

PMID- 26220698
TI  - Protein-Induced Color Shift of Carotenoids in beta-Crustacyanin.
AB  - beta-Crustacyanin (beta-CR) is a pigment protein responsible for the blue color
      of lobsters. We show using correlated ab initio calculations how the protein
      environment tunes the chromophores of beta-CR through electrostatic and steric
      effects. 

PMID- 26220699
TI  - Rare FOXC1 variants in congenital glaucoma: identification of translation
      regulatory sequences.
AB  - Primary congenital glaucoma (PCG) is the cause of a significant proportion of
      inherited visual loss in children, but the underlying mechanism is poorly
      understood. In this study, we assessed the relationship between PCG and FOXC1
      variants by Sanger sequencing the proximal promoter and transcribed sequence of
      FOXC1 from a cohort of 133 PCG families with no known CYP1B1 or MYOC mutations.
      The pathogenicity of the identified variants was evaluated by functional
      analyses. Ten patients (7.5%) with no family history of glaucoma carried five
      different rare heterozygous FOXC1 variants with both increased (rs77888940:C>G,
      c.-429C>G, rs730882054:c.1134_144del(CGGCGGCGCGG), p.(G380Rfs*144) and
      rs35717904:A>T, c.*734A>T) and decreased (rs185790394: C>T, c.-244C>T and
      rs79691946:C>T, p.(P297S)) transactivation, ranging from 50 to 180% of the wild
      type activity. The five variants did not show monogenic segregation, and four of
      them were absent in a control group (n=233). To the best of our knowledge, one of
      these variants (p.(G380Rfs*144)) has not previously been described. One of the
      FOXC1 variant carriers (p.(P297S)) also coinherited a functionally altered rare
      PITX2 heterozygous variant (rs6533526:C>T, c.*454C>T). Bioinformatics and
      functional analyses provided novel information on three of these variants. c.
      429C>G potentially disrupts a consensus sequence for a terminal oligopyrimidine
      tract, whereas c.-244C>T may alter the RNA secondary structure in the 5'
      untranslated region (UTR) that affects mRNA translation. In addition,
      p.(G380Rfs*144) led to increased protein stability. In summary, these data reveal
      the presence of translation regulatory sequences in the UTRs of FOXC1 and provide
      evidence for a possible role of rare FOXC1 variants as modifying factors of
      goniodysgenesis in PCG. 

PMID- 26220700
TI  - Attitudes of cystic fibrosis patients and parents toward carrier screening and
      related reproductive issues.
AB  - Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting ~1
      in 2500-4000 Caucasians. As most CF patients have no family history of the
      disorder, carrier screening for CF has the potential to prospectively identify
      couples at risk of conceiving an affected child. At-risk couples may consequently
      choose to act on the provided information and take steps to avoid the birth of a
      child with CF. Although carrier screening is widely believed to enhance
      reproductive autonomy of prospective parents, the practice also raises important
      ethical questions. A written questionnaire was administered to adult patients and
      parents of children with CF with the aim to explore participants' attitudes
      toward CF carrier screening and related reproductive issues. The study population
      was recruited from a CF patient registry in Belgium and comprised 111
      participants (64 parents, 47 patients aged 16 or older). We found that more than
      80% of all participants were in favor of preconception carrier screening for CF.
      However, some were concerned over potential negative consequences of population
      wide CF carrier screening. Regarding future reproductive intentions, 43% of the
      participants indicated a desire to have children. Among these, preimplantation
      genetic diagnosis was found to be the most preferred reproductive option, closely
      followed by spontaneous pregnancy and prenatal diagnosis. Although the findings
      of our study suggest that patients and parents of children with CF support a
      population-based carrier screening program for CF, they also highlight some
      issues deserving particular attention when implementing such a program. 

PMID- 26220702
TI  - Allocentric and egocentric manipulations of the sense of self-location in full
      body illusions and their relation with the sense of body ownership.
AB  - Self-location refers to the experience of occupying a given position in the
      environment. Recent research has addressed the sense of self-location as one of
      the key components of self-consciousness, together with the experience of owning
      the physical body (ownership) (Blanke and Metzinger, Trends Cogn Sci 13:7-13 in
      2009. doi: 10.1016/j.tics.2008.10.003 ). Experimentally controlled full-body
      illusions proved to be valuable research tools to study these components and
      their interaction, and to explore their underlying neural underpinning. The focus
      of this manuscript is to provide a close look into the nuances of different
      illusory experiences affecting the sense of self-location and to examine their
      relation to the concurrent experienced sense of body ownership. On the basis of
      previous reviewed studies, it is proposed that the sense of self-location may be
      regarded as the blending of two paralllel representations: the abstract
      allocentric coding of the position occupied in the environment, mainly associated
      with visual-perspective, and the egocentric mapping of somatosensory sensations
      into the external space, mainly associated with peripersonal space. Open
      questions to be addressed by future research are further addressed.

PMID- 26220701
TI  - Increased genetic risk for obesity in premature coronary artery disease.
AB  - There is ongoing controversy as to whether obesity confers risk for CAD
      independently of associated risk factors including diabetes mellitus. We have
      carried out a Mendelian randomization study using a genetic risk score (GRS) for
      body mass index (BMI) based on 35 risk alleles to investigate this question in a
      population of 5831 early onset CAD cases without diabetes mellitus and 3832
      elderly healthy control subjects, all of strictly European ancestry, with
      adjustment for traditional risk factors (TRFs). We then estimated the genetic
      correlation between these BMI and CAD (rg) by relating the pairwise genetic
      similarity matrix to a phenotypic covariance matrix between these two traits.
      GRSBMI significantly (P=2.12 * 10(-12)) associated with CAD status in a
      multivariate model adjusted for TRFs, with a per allele odds ratio (OR) of 1.06
      (95% CI 1.042-1.076). The addition of GRSBMI to TRFs explained 0.75% of CAD
      variance and yielded a continuous net recombination index of 16.54% (95% CI=11.82
      21.26%, P<0.0001). To test whether GRSBMI explained CAD status when adjusted for
      measured BMI, separate models were constructed in which the score and BMI were
      either included as covariates or not. The addition of BMI explained ~1.9% of CAD
      variance and GRSBMI plus BMI explained 2.65% of CAD variance. Finally, using
      bivariate restricted maximum likelihood analysis, we provide strong evidence of
      genome-wide pleiotropy between obesity and CAD. This analysis supports the
      hypothesis that obesity is a causal risk factor for CAD. 

PMID- 26220703
TI  - Dynamic competition and binding of concepts through time and space.
AB  - Models of implicit stereotypes (e.g., association of male with math or female
      with language) usually explain the faster responses observed for stereotype
      congruent trials in the Implicit Association Test (IAT) by requiring a
      fundamental opposition between the male and female concepts (or math-language),
      limiting the decision-making dynamics to abstract dimensions. This paper
      introduces alternate models exploiting the sensorimotor dimensions of the IAT,
      which naturally account for the opposition between concepts, because typically
      mapped on opposite corners of the screen space and on different response actions.
      In addition to the emergence of the IAT effect, dynamic characteristics of the
      decision-making process within these models are tested against human data,
      obtained with a mouse-tracking adapted IAT procedure.

PMID- 26220704
TI  - Prior knowledge of character locational stereotypes and representations during
      text comprehension.
AB  - Certain character locational stereotypes are expected to affect constructions of
      mental representations during text comprehension. The present study examined
      whether readers' prior knowledge of character locational stereotypes affects the
      construction of these character representations during text comprehension. Two
      short stories were presented to the participants. In one story, God, and two
      people wearing blue and green clothes, respectively, appeared in a room in that
      order (God condition). In the other, three people appeared in red, blue, and
      green clothes, respectively (three-people condition). The only difference between
      the two stories was the first character that appeared in the room. All
      participants were assigned to either the God or three-people condition.
      Participants read the story and provided an account of their own mental
      representation of where the three characters were located within the room, and
      explained the reasoning behind their descriptions. In the God condition, most
      participants stated that God was in the center (relative to the two people)
      because of locational stereotypes of God. In the three-people condition, most
      participants stated that the person in red was located in front of or closest to
      the participant because of the order in which the character appeared in the text.
      These results show that readers' prior knowledge of character locational
      stereotypes affects their mental representation of spatial relationships between
      characters during text comprehension. 

PMID- 26220705
TI  - Optomechanical measurement of the stiffness of single adherent cells.
AB  - Recent advances in mechanobiology have accumulated strong evidence showing close
      correlations between the physiological conditions and mechanical properties of
      cells. In this paper, a novel optomechanical technique to characterize the
      stiffness of single adherent cells attached on a substrate is reported. The
      oscillation in a cell's height on a vertically vibrating reflective substrate is
      measured with a laser Doppler vibrometer as apparent changes in the phase of the
      measured velocity. This apparent phase shift and the height oscillation are shown
      to be affected by the mechanical properties of human colorectal adenocarcinoma
      cells (HT-29). The reported optomechanical technique can provide high-throughput
      stiffness measurement of single adherent cells over time with minimal
      perturbation. 

PMID- 26220706
TI  - Intracellular survival of Burkholderia cepacia complex in phagocytic cells.
AB  - Burkholderia cepacia complex (Bcc) species are a group of Gram-negative
      opportunistic pathogens that infect the airways of cystic fibrosis patients, and
      occasionally they infect other immunocompromised patients. Bcc bacteria display
      high-level multidrug resistance and chronically persist in the infected host
      while eliciting robust inflammatory responses. Studies using macrophages,
      neutrophils, and dendritic cells, combined with advances in the genetic
      manipulation of these bacteria, have increased our understanding of the molecular
      mechanisms of virulence in these pathogens and the molecular details of cell-host
      responses triggering inflammation. This article discusses our current view of the
      intracellular survival of Burkholderia cenocepacia within macrophages. 

PMID- 26220707
TI  - Experimental Study of the Pathogenicity of Pasteurella multocida Capsular Type B
      in Rabbits.
AB  - The increased frequency of isolation of Pasteurella multocida capsular type B
      from rabbitries in north-western India prompted this investigation into the role
      of this organism in inducing disease in rabbits. Ten rabbits were divided into
      two groups of five animals. Group I rabbits were infected intranasally (IN) with
      1 ml of inoculum containing 2 * 10(5) colony forming units/ml, while rabbits in
      group II were given 1 ml phosphate buffered saline IN. The rabbits in group I
      developed respiratory distress, increased rectal temperature and severe dyspnoea,
      with death occurring 24-48 h post infection. The main pathological findings were
      severe congestion and haemorrhage in the trachea, fibrinopurulent pneumonia,
      bacteraemia and septicaemia. The nasal secretions of all group I animals
      contained P. multocida. These observations indicate that in addition to P.
      multocida capsular types A and D, P. multocida capsular type B can also be highly
      pathogenic for rabbits. 

PMID- 26220708
TI  - Neutral details associated with emotional events are encoded: evidence from a
      cued recall paradigm.
AB  - Enhanced emotional memory often comes at the cost of memory for surrounding
      background information. Narrowed-encoding theories suggest that this is due to
      narrowed attention for emotional information at encoding, leading to impaired
      encoding of background information. Recent work has suggested that an encoding
      based theory may be insufficient. Here, we examined whether cued recall-instead
      of previously used recognition memory tasks-would reveal evidence that non
      emotional information associated with emotional information was effectively
      encoded. Participants encoded positive, negative, or neutral objects on neutral
      backgrounds. At retrieval, they were given either the item or the background as a
      memory cue and were asked to recall the associated scene element. Counter to
      narrowed-encoding theories, emotional items were more likely than neutral items
      to trigger recall of the associated background. This finding suggests that there
      is a memory trace of this contextual information and that emotional cues may
      facilitate retrieval of this information.

PMID- 26220709
TI  - Facilitating collaboration in rare genetic disorders through effective
      matchmaking in DECIPHER.
AB  - DECIPHER (https://decipher.sanger.ac.uk) is a web-based platform for secure
      deposition, analysis, and sharing of plausibly pathogenic genomic variants from
      well-phenotyped patients suffering from genetic disorders. DECIPHER aids clinical
      interpretation of these rare sequence and copy-number variants by providing tools
      for variant analysis and identification of other patients exhibiting similar
      genotype-phenotype characteristics. DECIPHER also provides mechanisms to
      encourage collaboration among a global community of clinical centers and
      researchers, as well as exchange of information between clinicians and
      researchers within a consortium, to accelerate discovery and diagnosis. DECIPHER
      has contributed to matchmaking efforts by enabling the global clinical genetics
      community to identify many previously undiagnosed syndromes and new disease
      genes, and has facilitated the publication of over 700 peer-reviewed scientific
      publications since 2004. At the time of writing, DECIPHER contains anonymized
      data from ~250 registered centers on more than 51,500 patients (~18000 patients
      with consent for data sharing and ~25000 anonymized records shared privately). In
      this paper, we describe salient features of the platform, with special emphasis
      on the tools and processes that aid interpretation, sharing, and effective
      matchmaking with other data held in the database and that make DECIPHER an
      invaluable clinical and research resource. 

PMID- 26220710
TI  - The MIOREX complex--lean management of mitochondrial gene expression.

PMID- 26220711
TI  - Redefining protein moonlighting.

PMID- 26220713
TI  - A comprehensive study of the association between drug hepatotoxicity and daily
      dose, liver metabolism, and lipophilicity using 975 oral medications.
AB  - It was recently suggested that daily dose, liver metabolism and lipophilicity
      were associated with an oral drug's potential to cause hepatotoxicity, but this
      has not been widely accepted. A likely reason is that published data lack
      comprehensiveness, as they were based on only about one third of all FDA approved
      single-active-ingredient oral prescription drugs. Here the 975 oral drugs used
      worldwide which have a Defined Daily Dose (DDD) designated in the World Health
      Organization's Anatomical Therapeutic Chemical classification system and whose
      hADRs potential and metabolism data are available in the Micromedex Drugdex(r)
      compendium were studied, with their lipophilicity calculated by the partition
      coefficient LogP. Of the 975 drugs examined, 49% (478) have the potential to
      induce at least one type of hepatic adverse drug reactions (hADRs) such as fatal
      hepatotoxicity, acute liver failure, significant ALT/AST elevation, hepatitis,
      and jaundice. By single factor analysis, a higher DDD (>=100 mg) was found to be
      associated with all types of hADRs, and extensive liver metabolism (>=50%) was
      associated with a subset of hADRs including fatal hADRs, hepatitis and jaundice,
      while LogP showed no relation to any types of hADRs. Contrary to previous
      reports, none of the combination, neither DDD and liver metabolism, nor DDD and
      LogP, was found to be more predictive of hADRs than using DDD or liver metabolism
      alone. These data provide convincing evidence that a higher daily dose and
      extensive liver metabolism, but not lipophilicity, are independent but not
      synergistic risk factors for oral drugs to induce hepatotoxicity. 

PMID- 26220712
TI  - Circadian disruption and breast cancer: an epigenetic link?
AB  - Breast cancer is already the most common malignancy affecting women worldwide,
      and evidence is mounting that breast cancer induced by circadian disruption (CD)
      is a warranted concern. Numerous studies have investigated various aspects of the
      circadian clock in relation to breast cancer, and evidence from these studies
      indicates that melatonin and the core clock genes can play a crucial role in
      breast cancer development. Even though epigenetics has been increasingly
      recognized as a key player in the etiology of breast cancer and linked to
      circadian rhythms, and there is evidence of overlap between epigenetic
      deregulation and breast cancer induced by circadian disruption, only a handful of
      studies have directly investigated the role of epigenetics in CD-induced breast
      cancer. This review explores the circadian clock and breast cancer, and the
      growing role of epigenetics in breast cancer development and circadian rhythms.
      We also summarize the current knowledge and next steps for the investigation of
      the epigenetic link in CD-induced breast cancer. 

PMID- 26220714
TI  - Prognostic role of IDH mutations in gliomas: a meta-analysis of 55 observational
      studies.
AB  - BACKGROUND: IDH (Isocitrate dehydrogenase) mutations occur frequently in gliomas,
      but their prognostic impact has not been fully assessed. We performed a meta
      analysis of the association between IDH mutations and survival in gliomas.
      METHODS: Pubmed and EMBASE databases were searched for studies reporting IDH
      mutations (IHD1/2 and IDH1) and survival in gliomas. The primary outcome was
      overall survival (OS); the secondary outcome was progression-free survival (PFS).
      Hazard ratios (HR) with 95% confidence interval (CI) were determined using the
      Mantel-Haenszel random-effect modeling. Funnel plot and Egger's test were
      conducted to examine the risk of publication bias. RESULTS: Fifty-five studies
      (9487 patients) were included in the analysis. Fifty-four and twenty-seven
      studies investigated the association between IDH1/2 mutations and OS/PFS
      respectively in patients with glioma. The results showed that patients possessing
      an IDH1/2 mutation had significant advantages in OS (HR = 0.39, 95%CI: 0.34-0.45;
      P < 0.001) and PFS (HR = 0.42, 95% CI: 0.35-0.51; P < 0.001). Subgroup analysis
      showed a consistent result with pooled analysis, and patients with glioma of WHO
      grade III or II-III had better outcomes. CONCLUSIONS: These findings provide
      further indication that patients with glioma harboring IDH mutations have
      improved OS and PFS, especially for patients with WHO grade III and grade II-III.

PMID- 26220716
TI  - Development of a functionalized polymeric ionic liquid monolith for solid-phase
      microextraction of polar endocrine disrupting chemicals in aqueous samples
      coupled to high-performance liquid chromatography.
AB  - Ionic liquids (ILs) have been efficiently used as a "designer sorbent" in sample
      preparation. A novel 1-(3-aminopropyl)-3-(4-vinylbenzyl)imidazolium 4
      styrenesulfonate IL monomer was synthesized and copolymerized with 1,6-di(3
      vinylimidazolium) hexane bishexafluorophosphate IL as cross-linking agent to
      prepare a cross-linked polymeric ionic liquids (PILs) monolith. Coupled to high
      performance liquid chromatography (HPLC), the PILs monolith was used as a solid
      phase microextraction (SPME) sorbent to extract some polar endocrine disrupting
      chemical (EDCs) such as estrogens, bisphenol A, and phthalate esters in aqueous
      samples. Preparation and extraction conditions were investigated and optimized to
      obtain satisfactory extraction efficiency. Limits of detection (LODs) of the
      proposed method for three steroid estrogens and bisphenol A were 0.25 and 0.2 MUg
      L(-1), respectively, which were lower than or comparable to some other sample
      preparation methods. Intra- and inter-day repeatability for all the analytes was
      2.2-12%. The monolith-to-monolith repeatability was 7.4-15%. The extraction
      performance of the method for analysis of target estrogens in treated domestic
      wastewater was investigated and compared with a dispersive liquid-liquid
      microextraction (DLLME) method. The proposed SPME method provided better
      sensitivity and higher resistance to matrix interferences.

PMID- 26220715
TI  - Improving surface and defect center chemistry of fluorescent nanodiamonds for
      imaging purposes--a review.
AB  - Diamonds are widely used for jewelry owing to their superior optical properties
      accounting for their fascinating beauty. Beyond the sparkle, diamond is highly
      investigated in materials science for its remarkable properties. Recently,
      fluorescent defects in diamond, particularly the negatively charged nitrogen
      vacancy (NV(-)) center, have gained much attention: The NV(-) center emits
      stable, nonbleaching fluorescence, and thus could be utilized in biolabeling, as
      a light source, or as a Forster resonance energy transfer donor. Even more
      remarkable are its spin properties: with the fluorescence intensity of the NV(-)
      center reacting to the presence of small magnetic fields, it can be utilized as a
      sensor for magnetic fields as small as the field of a single electron spin.
      However, a reproducible defect and surface and defect chemistry are crucial to
      all applications. In this article we review methods for using nanodiamonds for
      different imaging purposes. The article covers (1) dispersion of particles, (2)
      surface cleaning, (3) particle size selection and reduction, (4) defect
      properties, and (5) functionalization and attachment to nanostructures, e.g.,
      scanning probe microscopy tips.

PMID- 26220717
TI  - Development of a Targeted Urine Proteome Assay for kidney diseases.
AB  - PURPOSE: Since human urine is the most readily available biofluid whose proteome
      changes in response to disease, it is a logical sample for identifying protein
      biomarkers for kidney diseases. EXPERIMENTAL DESIGN: Potential biomarkers were
      identified by using a multiproteomics workflow to compare urine proteomes of
      kidney transplant patients with immediate and delayed graft function.
      Differentially expressed proteins were identified, and corresponding stable
      isotope labeled internal peptide standards were synthesized for scheduled MRM.
      RESULTS: The Targeted Urine Proteome Assay (TUPA) was then developed by
      identifying those peptides for which there were at least two transitions for
      which interference in a urine matrix across 156 MRM runs was <30%. This resulted
      in an assay that monitors 224 peptides from 167 quantifiable proteins.
      CONCLUSIONS AND CLINICAL RELEVANCE: TUPA opens the way for using a robust mass
      spectrometric technology, MRM, for quantifying and validating biomarkers from
      among 167 urinary proteins. This approach, while developed using differentially
      expressed urinary proteins from patients with delayed versus immediate graft
      function after kidney transplant, can be expanded to include differentially
      expressed urinary proteins in multiple kidney diseases. Thus, TUPA could provide
      a single assay to help diagnose, prognose, and manage many kidney diseases.

PMID- 26220718
TI  - Psychiatric inpatient care: where do we go from here?
AB  - The significant decline in the number of psychiatric hospital beds for more than
      two decades across Europe has changed the landscape of mental health services.
      This has rekindled debates about bed shortages and the reasons for variations in
      the number of inpatient beds, admissions to hospital and length of stay. Analysis
      of European Union (EU) level data shows that the UK has a relatively low number
      of admissions to hospital, yet a much higher than average length of stay compared
      with 12 other EU Member States. Understanding this is difficult, but recent
      studies shed some further light on the patterns and predictors of admissions and
      length of stay. 

PMID- 26220727
TI  - Prevalence of Class 1 Integrons and Extended Spectrum Beta Lactamases among Multi
      Drug Resistant Escherichia coli Isolates from North of Iran.
AB  - BACKGROUND: Extended spectrum beta lactamases (ESBLs) are an important cause of
      transferable multidrug resistance (MDR) in gram-negative bacteria. The most
      described ESBL genes are generally found within integron-like structures as
      mobile genetic elements. The aim of this study was to identify the accompanying
      of class 1 integrons and ESBLs in the MDR E. coli isolates. METHODS:
      Susceptibility to antimicrobial agents was determined for 33 E. coli strains by
      the disk diffusion method. Double-disk synergy test was applied for screening
      ESBL. To identify the strains carrying integrons, the conserved regions of
      integron-encoded integrase gene intI1 were amplified. For detection of gene
      cassettes, 5'CS and 3'CS primers were used. RESULTS: All E. coli isolates were
      identified as multi-drug resistant. More than 50% of the isolates were resistant
      to tetracycline, cephalothin, cefuroxime, amoxicillin-clavulanic acid, and third
      generation cephalosporines. Nearly all of the isolates displayed sensitivity to
      piperacillin. There was a significant correlation between production of ESBL and
      resistance to all antibiotics except for ciprofloxacin and piperacillin (P value
      less than 0.01). Thirty two MDR strains (97%) included class 1 integron, and some
      isolates that included integrons were similar in the size of gene cassettes. The
      isolates were different in the resistance profiles; however, some others had
      similar resistance profiles. Of eight ESBL positive isolates, seven (87.5%)
      carried class 1 integrons. CONCLUSION: Class 1 integrons were frequent in MDR and
      also ESBL-producing E. coli isolates. High prevalence of class 1 integrons
      confirms that integron-mediated antimicrobial gene cassettes are important in E.
      coli resistance profile.

PMID- 26220728
TI  - Serum ficolin-2 concentrations are significantly changed in patients with
      hepatitis B virus infection and liver diseases.
AB  - Human ficolin-2 is an important lectin complement pathway activator that is
      secreted from liver cells and has been implicated as an anti-infection innate
      immune molecule. However, the role of ficolin-2 protein and its dynamic changes
      over the course of and in the prognosis of chronic hepatitis B (CHB) and
      hepatocellular carcinoma (HCC) remain unclear. In this study, we analyzed ficolin
      2 protein expression in a cohort of individuals with CHB infection, HCC and
      cirrhosis. A sandwich enzyme-linked immunosorbent assay (ELISA) method was used
      to measure serum ficolin-2 concentrations. Ficolin-2 expression in liver tissues
      was detected by immunohistochemical staining. Serum ficolin-2 concentrations in
      CHB patients were significantly higher than in healthy controls and HBV carriers.
      After 48 weeks of routine amelioration liver function treatment, serum ficolin-2
      concentrations decreased and were positively correlated with favorable alanine
      aminotransferase (ALT), HBV DNA and HBeAg-seroconversion outcomes. Interestingly,
      we observed much lower expression of serum and intrahepatic ficolin-2 in HCC and
      cirrhosis compared with healthy controls. Our findings suggest that serum and
      intrahepatic ficolin-2 levels may be considered one of the indicators for the
      response of chronic HBV infection, HCC and cirrhosis. 

PMID- 26220729
TI  - Development and characterization of a clinical strain of Coxsackievirus A16 and
      an eGFP infectious clone.
AB  - Coxsackievirus A16 (CA16) is one of the major causes of hand, foot, and mouth
      disease (HFMD) worldwide, which is a common illness that affects children. The
      frequent occurrence of HFMD outbreaks has become a serious public health problem
      in Asia. Therefore, it is important to understand the pathogenesis and
      replication of CA16. In this study, a stable infectious cDNA clone of an epidemic
      strain of Coxsackievirus A16 (CA16) was assembled, and subsequently a reporter
      virus (eGFP-CA16) was constructed by inserting the eGFP gene between the 5'-UTR
      and the N-terminus of VP4, with the addition of a 2A protease cleavage site
      (ITTLG) at its C-terminus. This was transfected into Vero cells to generate
      infectious recombinant viruses. The growth characteristics and plaque morphology,
      in vitro, in mammalian cells were found to be indistinguishable between the
      parental and recombinant viruses. Although the eGFP-CA16 showed smaller plaque
      size as compared to recombinant CA16, both were found to exhibit similar growth
      trends and EC50 of NITD008. In summary, this stable infectious cDNA clone should
      provide a valuable experimental system to study CA16 infection and host response.
      The eGFP-CA16 is expected to provide a powerful tool to monitor eGFP expression
      in infected cells and to evaluate the antiviral activity of potential antiviral
      agents in the treatment of CA16 infections.

PMID- 26220730
TI  - The bidirectional interactions between psoriasis and obstructive sleep apnea.
AB  - Psoriasis is a chronic inflammatory skin disorder which can impair general
      routine activities and has been closely related to poor quality of life. Pruritus
      and scratching are frequently observed, occurring mainly during sleep and
      precipitating nighttime arousals. Indeed, sleep quality has been shown to be
      negatively affected in psoriatic patients, in a close relationship with stress
      exposure and immune response. Although psoriasis is known to impair sleep,
      leading to insomnia, its association with obstructive sleep apnea (OSA) is
      controversial. Similarly, OSA is considered a multifactorial inflammatory
      disease, characterized by intermittent hypoxia, sleep fragmentation and autonomic
      dysfunction, with important outcomes on the cardiovascular and metabolic systems.
      Importantly, immunological activities and pro-inflammatory cytokines play a
      prominent role in both OSA and psoriasis. Currently it is not clear whether OSA
      is a risk factor for psoriasis development or if psoriasis is a possible
      predictor of OSA. Thus, our main purpose is to provide an overview of this
      intriguing relationship and show the current link between psoriasis and OSA in a
      bidirectional relationship.

PMID- 26220731
TI  - Early haemodynamic changes observed in patients with epilepsy, in a visual
      experiment and in simulations.
AB  - OBJECTIVE: The objective of this study was to investigate whether previously
      reported early blood oxygen level dependent (BOLD) changes in epilepsy could
      occur as a result of the modelling techniques rather than physiological changes.
      METHODS: EEG-fMRI data were analysed from seven patients with focal epilepsy, six
      control subjects undergoing a visual experiment, in addition to simulations. In
      six separate analyses the event timing was shifted by either -9,-6,-3,+3,+6 or +9
      s relative to the onset of the interictal epileptiform discharge (IED) or
      stimulus. RESULTS: The visual dataset and simulations demonstrated an overlap
      between modelled haemodynamic response function (HRF) at event onset and at +/- 3
      s relative to onset, which diminished at +/- 6s. Pre-spike analysis at -6s
      improved concordance with the assumed IED generating lobe relative to the
      standard HRF in 43% of patients. CONCLUSION: The visual and simulated dataset
      findings indicate a form of "temporal bleeding", an overlap between the modelled
      HRF at time 0 and at +/- 3s which attenuated at +/- 6s. Pre-spike analysis at -6s
      may improve concordance. SIGNIFICANCE: This form of analysis should be performed
      at 6s prior to onset of IED to minimise temporal bleeding effect. The results
      support the presence of relevant BOLD responses occurring prior to IEDs.

PMID- 26220732
TI  - Ultrasound and electrophysiologic findings in patients with Guillain-Barre
      syndrome at disease onset and over a period of six months.
AB  - OBJECTIVE: To investigate cross-sectional areas (CSAs) of several peripheral
      nerves including the vagus nerve and the diameter of spinal nerves as measured by
      nerve ultrasound (NUS) and nerve conduction studies (NCS) in Guillain-Barre
      syndrome (GBS) patients over at least six months compared to healthy controls.
      METHODS: NUS and/or NCS of several nerves, the vagus nerve, and the 5th/6th
      cervical spinal nerves were performed in patients with GBS at days 2-3 after
      symptom onset, at days 10-14 after immunoglobulin therapy and after six months
      compared to healthy controls. RESULTS: 27 GBS-patients and 31 controls were
      included. Using NUS significant enlargement was found in all measured nerves
      (P<0.001), except the sural nerve (P=0.086) compared to the controls at onset.
      The vagus (median 3.0 mm(2) vs. 2.0 mm(2), P<0.0001) and the cervical spinal
      nerves were significantly enlarged (median 3.5/4.0 mm vs. 2.6/3.2 mm, p<0.0001),
      the vagus most obviously in patients with autonomic dysregulation (AD, 4.0
      mm(2)). Six months later, NCS showed persisting pathology in CMAP-amplitudes with
      amelioration of F-wave pathology. NUS showed restitution in the spinal nerves
      (median 2.6/3.2 mm) and the vagus (median 2.0 mm(2)) in all patients excluding
      the vagus in those with persistent AD (median 4.0 mm(2)). The peripheral nerves
      did not change significantly (P>0.05). CONCLUSION: Ultrasonographic detection of
      cervical spinal nerve enlargement supports the diagnosis of GBS in the early
      phase. Its regression may be a good parameter for the clinical restitution over
      time. Vagus enlargement may be a risk marker for development of AD. SIGNIFICANCE:
      Ultrasound is a reliable diagnostic follow-up tool in early GBS.

PMID- 26220733
TI  - In vivo bone formation by and inflammatory response to resorbable polymer
      nanoclay constructs.
AB  - The development of synthetic bone grafts with requisite mechanical and
      morphological properties remains a key challenge in orthopaedics. Supercritical
      carbon dioxide (scCO2)-processed nanocomposites consisting of organically
      modified montmorillonite clay dispersed in poly-d-lactide (PDLA) have shown
      structural and mechanical properties similar to corticocancellous bone. Using
      quantitative undecalcified histology and micro-computed tomography (MUCT), time
      and material-dependent influences on in vivo bone formation, and inflammatory
      response were characterized. This represents the first in vivo evidence of the
      ability of scCO2-processed PDLA-nanoclay constructs to support osteogenesis,
      while eliciting an inflammatory response comparable to PDLA-hydroxyapatite
      materials. Histologic analyses demonstrated that the in vivo performance of
      nanoclay-containing PDLA constructs was similar to pure PDLA constructs, though
      nanocomposites demonstrated more radiodense bone at all time points (MUCT
      analysis), and higher bone volume at 6 weeks. Taken with previous structural and
      mechanical studies, these in vivo analyses suggest that scCO2-processed, polymer
      clay nanocomposites may be suitable structural bone graft materials. FROM THE
      CLINICAL EDITOR: With advances in science, orthopedic researchers have devoted
      significant amount of time in developing synthetic bone graft materials. Many of
      which are indeed currently in clinical use. In their previous studies, the
      authors described and studied supercritical carbon dioxide (scCO2)-processed
      nanocomposites consisting of organically modified montmorillonite clay dispersed
      in poly-D-lactide (PDLA) in in-vitro experiments. Here, in-vivo experiments were
      performed to investigate if this new material had improved mechanical properties,
      as well as the induction of inflammatory response. The overall positive findings
      may mean that this material could be used for future bone graft substitute
      applications.

PMID- 26220734
TI  - Circulating Inflammation Markers, Risk of Lung Cancer, and Utility for Risk
      Stratification.
AB  - BACKGROUND: We conducted two independent nested case-control studies to identify
      circulating inflammation markers reproducibly associated with lung cancer risk
      and to investigate the utility of replicated markers for lung cancer risk
      stratification. METHODS: Nested within the Prostate, Lung, Colorectal, and
      Ovarian Cancer Screening Trial, the previously published discovery study included
      526 lung cancer patients and 592 control subjects and the replication study
      included 526 lung cancer case patients and 625 control subjects. Control subjects
      were matched by sex, age, smoking, study visit, and years of blood draw and exit.
      Serum levels of 51 inflammation markers were measured. Odds ratios (ORs) were
      estimated with conditional logistic regression. All statistical tests were two
      sided. RESULTS: Of 11 markers identified in the discovery study, C-reactive
      protein (CRP) (odds ratio [OR] [highest vs. lowest category] = 1.77, 95%
      confidence interval [CI] = 1.23 to 2.54), serum amyloid A (SAA) (OR = 1.88, 95%
      CI = 1.28 to 2.76), soluble tumor necrosis factor receptor-2 (sTNFRII) (OR =
      1.70, 95% CI = 1.18 to 2.45), and monokine induced by gamma interferon
      (CXCL9/MIG) (OR = 2.09, 95% CI = 1.41 to 3.00) were associated with lung cancer
      risk in the replication study (P trend < .01). In pooled analyses, CRP, SAA, and
      CXCL9/MIG remained associated with lung cancer more than six years before
      diagnosis (P trend < .05). The incorporation of an inflammation score combining
      these four markers did not improve the sensitivity (77.6% vs 75.8%, P = .33) or
      specificity (56.1% vs 56.1%, P = .98) of risk-based lung cancer models.
      CONCLUSIONS: Circulating levels of CRP, SAA, sTNFRII, and CXCL9/MIG were
      reproducibly associated with lung cancer risk in two independent studies within
      the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, underscoring
      an etiologic role for inflammation in lung carcinogenesis, though replication is
      needed in other populations. Markers did not improve lung cancer risk
      stratification beyond standard demographic and behavioral characteristics.

PMID- 26220735
TI  - Racial Disparities in Colorectal Cancer Survival: Is Elimination of Variation in
      Care the Cure?

PMID- 26220737
TI  - Susceptibility to the pinewood nematode (PWN) of four pine species involved in
      potential range expansion across Europe.
AB  - The pine wilt disease (PWD), caused by the pinewood nematode (PWN)
      Bursaphelenchus xylophilus (Steiner et Buhrer) Nickle, is one of the most serious
      threats to pine forests worldwide. Here we studied several components of
      susceptibility to PWN infection in a model group of pine species widely
      distributed in Europe (Pinus pinaster Ait., P. pinea L., P. sylvestris L. and P.
      radiata D. Don), specifically concerning anatomical and chemical traits
      putatively related to nematode resistance, whole-plant nematode population after
      experimental inoculation, and several biochemical and physiological traits
      indicative of plant performance, damage and defensive responses 60 days post
      inoculation (dpi) in 3-year-old plants. Pinus pinaster was the most susceptible
      species to PWN colonization, with a 13-fold increase in nematode population size
      following inoculation, showing up to 35-fold more nematodes than the other
      species. Pinus pinea was the most resistant species, with an extremely reduced
      nematode population 60 dpi. Axial resin canals were significantly wider in P.
      pinaster than in the other species, which may have facilitated nematode dispersal
      through the stem and contributed to its high susceptibility; nevertheless, this
      trait does not seem to fully determinate the susceptible character of a species,
      as P. sylvestris showed similar nematode migration rates to P. pinaster but
      narrower axial resin canals. Nematode inoculation significantly affected stem
      water content and polyphenolic concentration, and leaf chlorophyll and lipid
      peroxidation in all species. In general, P. pinaster and P. sylvestris showed
      similar chemical responses after infection, whereas P. radiata, which co-exists
      with the PWN in its native range, showed some degree of tolerance to the
      nematode. This work provides evidence that the complex interactions between B.
      xylophilus and its hosts are species-specific, with P. pinaster showing a strong
      susceptibility to the pathogen, P. pinea being the most tolerant species, and P.
      sylvestris and P. radiata having a moderate susceptibility, apparently through
      distinct coping mechanisms. 

PMID- 26220736
TI  - Addition of a single methyl group to a small molecule sodium channel inhibitor
      introduces a new mode of gating modulation.
AB  - BACKGROUND AND PURPOSE: Aryl sulfonamide Nav 1.3 or Nav 1.7 voltage-gated sodium
      (Nav ) channel inhibitors interact with the Domain 4 voltage sensor domain (D4
      VSD). During studies to better understand the structure-activity relationship of
      this interaction, an additional mode of channel modulation, specifically slowing
      of inactivation, was revealed by addition of a single methyl moiety. The
      objective of the current study was to determine if these different modulatory
      effects are mediated by the same or distinct interactions with the channel.
      EXPERIMENTAL APPROACH: Electrophysiology and site-directed mutation were used to
      compare the effects of PF-06526290 and its desmethyl analogue PF-05661014 on Nav
      channel function. KEY RESULTS: PF-05661014 selectively inhibits Nav 1.3 versus
      Nav 1.7 currents by stabilizing inactivated channels via interaction with D4 VSD.
      In contrast, PF-06526290, which differs from PF-05661014 by a single methyl
      group, exhibits a dual effect. It greatly slows inactivation of Nav channels in a
      subtype-independent manner. However, upon prolonged depolarization to induce
      inactivation, PF-06526290 becomes a Nav subtype selective inhibitor similar to PF
      05661014. Mutation of the D4 VSD modulates inhibition of Nav 1.3 or Nav 1.7 by
      both PF-05661014 and PF-06526290, but has no effect on the inactivation slowing
      produced by PF-06526290. This finding, along with the absence of functional
      inhibition of PF-06526290-induced inactivation slowing by PF-05661014, suggests
      that distinct interactions underlie the two modes of Nav channel modulation.
      CONCLUSIONS AND IMPLICATIONS: Addition of a methyl group to a Nav channel
      inhibitor introduces an additional mode of gating modulation, implying that a
      single compound can affect sodium channel function in multiple ways.

PMID- 26220738
TI  - Temperature-dependent nanomorphology-performance relations in binary iridium
      complex blend films for organic light emitting diodes.
AB  - Understanding the mechanism responsible for the temperature-dependent
      performances of emitting layers is essential for developing advanced
      phosphorescent organic light emitting diodes. We described the morphological
      evolution occurring in PVK:Ir(ppy)3 binary blend films, with respect to thermal
      annealing up to 300  degrees C, by coupling atomic force microscopy and
      transmission electron microscopy. In particular, in situ temperature-dependent
      experimental characterization was performed to directly determine the overall
      sequence of morphological evolution occurring in the films. The device thermally
      annealed at 200  degrees C exhibits a noticeable enhancement in the performances,
      compared to the devices in the as-processed state and to the devices annealed at
      300  degrees C. Our approaches reveal that the Ir(ppy)3 molecules, with a needle
      like structure in the as-processed state, were aggregated, and thus diffused into
      PVK without a morphological change at the temperature regime between 150  degrees
      C and 200  degrees C. Moreover, both network-like and droplet patterns existed in
      the devices annealed at 300  degrees C, which was beyond the glass temperature of
      PVK, leading to a profound increase in the surface roughness. The observed
      pattern formation is discussed in terms of viscoelastic phase separation. Based
      on our experimental findings, we propose that the performances of the devices are
      significantly controlled by the diffusion of dopant molecules and the
      morphological evolution of the host materials in binary blend systems. 

PMID- 26220739
TI  - Autoantibodies to asialoglycoprotein receptor (ASGPR) in patients with autoimmune
      liver diseases.
AB  - BACKGROUND: The liver asialoglycoprotein receptor (ASGPR) is the only organ
      specific autoantigenic target in autoimmune hepatitis (AIH) patients and
      corresponding autoantibodies (Abs) have been suggested aiding in the serology of
      autoimmune liver diseases (ALD). METHODS: A novel enzyme-linked immunosorbent
      assay (ELISA) employing purified rabbit ASGPR was used to detect ASGPR Abs in
      patients with ALD and controls. ASGPR Ab was determined in sera from 172 patients
      with AIH type 1, AIH type 2 (n=42), primary biliary cirrhosis (PBC) (n=113),
      cryptogenic liver disease (n=30), toxic liver disease (n=11), primary sclerosing
      cholangitis (PSC) (n=27), HCV infection (n=25), non-alcoholic steatohepatitis
      (n=43) and 100 blood donors. ASGPR Ab positivity was compared with AIH-related
      Abs (ANA, ASMA, Abs to LKM-1, LC-1, and SLA/LP) in patients with AIH. RESULTS:
      Patients with AIH-1 and AIH-2 demonstrated an ASGPR Ab prevalence of 29.1% and
      16.7%, respectively. ASGPR Ab positivity in patients with AIH-1 and AIH-2 was not
      significantly different to those in patients with PSC and HCV (p>0.05,
      respectively). ASGPR Ab levels in all study cohorts were significantly different
      with the highest medians in patients with AIH, PSC, and HCV infection (p<0.0001).
      ASGPR Ab can be found as only AIH-specific Ab determined by LIA and ELISA in
      24.4% of AIH patients (48/197). CONCLUSIONS: The novel ASGPR Ab ELISA is a
      specific diagnostic tool for ASGPR Ab detection in AIH. In addition to AIH,
      patients with PSC can demonstrate elevated ASGPR Ab amongst those with ALD
      suggesting a tolerance break to ASGPR in PSC.

PMID- 26220740
TI  - Differential contributions of the globus pallidus and ventral thalamus to
      stimulus-response learning in humans.
AB  - The ability to learn associations between stimuli, responses and rewards is a
      prerequisite for survival. Models of reinforcement learning suggest that the
      striatum, a basal ganglia input nucleus, vitally contributes to these learning
      processes. Our recently presented computational model predicts, first, that not
      only the striatum, but also the globus pallidus contributes to the learning
      (i.e., exploration) of stimulus-response associations based on rewards. Secondly,
      it predicts that the stable execution (i.e., exploitation) of well-learned
      associations involves further learning in the thalamus. To test these
      predictions, we postoperatively recorded local field potentials (LFPs) from
      patients that had undergone surgery for deep brain stimulation to treat severe
      movement disorders. Macroelectrodes were placed either in the globus pallidus or
      in the ventral thalamus. During recordings, patients performed a reward-based
      stimulus-response learning task that comprised periods of exploration and
      exploitation. We analyzed correlations between patients' LFP amplitudes and model
      based estimates of their reward expectations and reward prediction errors. In
      line with our first prediction, pallidal LFP amplitudes during the presentation
      of rewards and reward omissions correlated with patients' reward prediction
      errors, suggesting pallidal access to reward-based teaching signals.
      Unexpectedly, the same was true for the thalamus. In further support of this
      prediction, pallidal LFP amplitudes during stimulus presentation correlated with
      patients' reward expectations during phases of low reward certainty - suggesting
      pallidal participation in the learning of stimulus-response associations. In line
      with our second prediction, correlations between thalamic stimulus-related LFP
      amplitudes and patients' reward expectations were significant within phases of
      already high reward certainty, suggesting thalamic participation in exploitation.

PMID- 26220741
TI  - Cross-modal reorganization in cochlear implant users: Auditory cortex contributes
      to visual face processing.
AB  - There is converging evidence that the auditory cortex takes over visual functions
      during a period of auditory deprivation. A residual pattern of cross-modal take
      over may prevent the auditory cortex to adapt to restored sensory input as
      delivered by a cochlear implant (CI) and limit speech intelligibility with a CI.
      The aim of the present study was to investigate whether visual face processing in
      CI users activates auditory cortex and whether this has adaptive or maladaptive
      consequences. High-density electroencephalogram data were recorded from CI users
      (n=21) and age-matched normal hearing controls (n=21) performing a face versus
      house discrimination task. Lip reading and face recognition abilities were
      measured as well as speech intelligibility. Evaluation of event-related potential
      (ERP) topographies revealed significant group differences over occipito-temporal
      scalp regions. Distributed source analysis identified significantly higher
      activation in the right auditory cortex for CI users compared to NH controls,
      confirming visual take-over. Lip reading skills were significantly enhanced in
      the CI group and appeared to be particularly better after a longer duration of
      deafness, while face recognition was not significantly different between groups.
      However, auditory cortex activation in CI users was positively related to face
      recognition abilities. Our results confirm a cross-modal reorganization for
      ecologically valid visual stimuli in CI users. Furthermore, they suggest that
      residual takeover, which can persist even after adaptation to a CI is not
      necessarily maladaptive. 

PMID- 26220742
TI  - Dynamic causal modelling of electrographic seizure activity using Bayesian belief
      updating.
AB  - Seizure activity in EEG recordings can persist for hours with seizure dynamics
      changing rapidly over time and space. To characterise the spatiotemporal
      evolution of seizure activity, large data sets often need to be analysed. Dynamic
      causal modelling (DCM) can be used to estimate the synaptic drivers of cortical
      dynamics during a seizure; however, the requisite (Bayesian) inversion procedure
      is computationally expensive. In this note, we describe a straightforward
      procedure, within the DCM framework, that provides efficient inversion of seizure
      activity measured with non-invasive and invasive physiological recordings;
      namely, EEG/ECoG. We describe the theoretical background behind a Bayesian belief
      updating scheme for DCM. The scheme is tested on simulated and empirical seizure
      activity (recorded both invasively and non-invasively) and compared with standard
      Bayesian inversion. We show that the Bayesian belief updating scheme provides
      similar estimates of time-varying synaptic parameters, compared to standard
      schemes, indicating no significant qualitative change in accuracy. The difference
      in variance explained was small (less than 5%). The updating method was
      substantially more efficient, taking approximately 5-10min compared to
      approximately 1-2h. Moreover, the setup of the model under the updating scheme
      allows for a clear specification of how neuronal variables fluctuate over
      separable timescales. This method now allows us to investigate the effect of fast
      (neuronal) activity on slow fluctuations in (synaptic) parameters, paving a way
      forward to understand how seizure activity is generated.

PMID- 26220743
TI  - Default mode network connectivity during task execution.
AB  - Initially described as task-induced deactivations during goal-directed paradigms
      of high attentional load, the unresolved functionality of default mode regions
      has long been assumed to interfere with task performance. However, recent
      evidence suggests a potential default mode network involvement in fulfilling
      cognitive demands. We tested this hypothesis in a finger opposition paradigm with
      task and fixation periods which we compared with an independent resting state
      scan using functional magnetic resonance imaging and a comprehensive analysis
      pipeline including activation, functional connectivity, behavioural and graph
      theoretical assessments. The results indicate task specific changes in the
      default mode network topography. Behaviourally, we show that increased
      connectivity of the posterior cingulate cortex with the left superior frontal
      gyrus predicts faster reaction times. Moreover, interactive and dynamic
      reconfiguration of the default mode network regions' functional connections
      illustrates their involvement with the task at hand with higher-level global
      parallel processing power, yet preserved small-world architecture in comparison
      with rest. These findings demonstrate that the default mode network does not
      disengage during this paradigm, but instead may be involved in task relevant
      processing. 

PMID- 26220744
TI  - Heterogeneity of arousals in human sleep: A stereo-electroencephalographic study.
AB  - Wakefulness, non-rapid eye movement (NREM), and rapid eye movement (REM) sleep
      are characterized by specific brain activities. However, recent experimental
      findings as well as various clinical conditions (parasomnia, sleep inertia) have
      revealed the presence of transitional states. Brief intrusions of wakefulness
      into sleep, namely, arousals, appear as relevant phenomena to characterize how
      brain commutes from sleep to wakefulness. Using intra-cerebral recordings in 8
      drug-resistant epileptic patients, we analyzed electroencephalographic (EEG)
      activity during spontaneous or nociceptive-induced arousals in NREM and REM
      sleep. Wavelet spectral analyses were performed to compare EEG signals during
      arousals, sleep, and wakefulness, simultaneously in the thalamus, and primary,
      associative, or high-order cortical areas. We observed that 1) thalamic activity
      during arousals is stereotyped and its spectral composition corresponds to a
      state in-between wakefulness and sleep; 2) patterns of cortical activity during
      arousals are heterogeneous, their manifold spectral composition being related to
      several factors such as sleep stages, cortical areas, arousal modality
      ("spontaneous" vs nociceptive-induced), and homeostasis; 3) spectral compositions
      of EEG signals during arousal and wakefulness differ from each other. Thus,
      stereotyped arousals at the thalamic level seem to be associated with different
      patterns of cortical arousals due to various regulation factors. These results
      suggest that the human cortex does not shift from sleep to wake in an abrupt
      binary way. Arousals may be considered more as different states of the brain than
      as "short awakenings." This phenomenon may reflect the mechanisms involved in the
      negotiation between two main contradictory functional necessities, preserving the
      continuity of sleep, and maintaining the possibility to react. 

PMID- 26220745
TI  - Medial prefrontal pathways for the contextual regulation of extinguished fear in
      humans.
AB  - The maintenance of anxiety disorders is thought to depend, in part, on deficits
      in extinction memory, possibly due to reduced contextual control of extinction
      that leads to fear renewal. Animal studies suggest that the neural circuitry
      responsible fear renewal includes the hippocampus, amygdala, and dorsomedial
      (dmPFC) and ventromedial (vmPFC) prefrontal cortex. However, the neural
      mechanisms of context-dependent fear renewal in humans remain poorly understood.
      We used functional magnetic resonance imaging (fMRI), combined with
      psychophysiology and immersive virtual reality, to elucidate how the hippocampus,
      amygdala, and dmPFC and vmPFC interact to drive the context-dependent renewal of
      extinguished fear. Healthy human participants encountered dynamic fear-relevant
      conditioned stimuli (CSs) while navigating through 3-D virtual reality
      environments in the MRI scanner. Conditioning and extinction were performed in
      two different virtual contexts. Twenty-four hours later, participants were
      exposed to the CSs without reinforcement while navigating through both contexts
      in the MRI scanner. Participants showed enhanced skin conductance responses
      (SCRs) to the previously-reinforced CS+ in the acquisition context on Day 2,
      consistent with fear renewal, and sustained responses in the dmPFC. In contrast,
      participants showed low SCRs to the CSs in the extinction context on Day 2,
      consistent with extinction recall, and enhanced vmPFC activation to the non
      reinforced CS-. Structural equation modeling revealed that the dmPFC fully
      mediated the effect of the hippocampus on right amygdala activity during fear
      renewal, whereas the vmPFC partially mediated the effect of the hippocampus on
      right amygdala activity during extinction recall. These results indicate
      dissociable contextual influences of the hippocampus on prefrontal pathways,
      which, in turn, determine the level of reactivation of fear associations. 

PMID- 26220746
TI  - Brain activity correlates with emotional perception induced by dynamic avatars.
AB  - An accurate judgment of the emotional state of others is a prerequisite for
      successful social interaction and hence survival. Thus, it is not surprising that
      we are highly skilled at recognizing the emotions of others. Here we aimed to
      examine the neuronal correlates of emotion recognition from gait. To this end we
      created highly controlled dynamic body-movement stimuli based on real human
      motion-capture data (Roether et al., 2009). These animated avatars displayed gait
      in four emotional (happy, angry, fearful, and sad) and speed-matched neutral
      styles. For each emotional gait and its equivalent neutral gait, avatars were
      displayed at five morphing levels between the two. Subjects underwent fMRI
      scanning while classifying the emotions and the emotional intensity levels
      expressed by the avatars. Our results revealed robust brain selectivity to
      emotional compared to neutral gait stimuli in brain regions which are involved in
      emotion and biological motion processing, such as the extrastriate body area
      (EBA), fusiform body area (FBA), superior temporal sulcus (STS), and the amygdala
      (AMG). Brain activity in the amygdala reflected emotional awareness: for visually
      identical stimuli it showed amplified stronger response when the stimulus was
      perceived as emotional. Notably, in avatars gradually morphed along an emotional
      expression axis there was a parametric correlation between amygdala activity and
      emotional intensity. This study extends the mapping of emotional decoding in the
      human brain to the domain of highly controlled dynamic biological motion. Our
      results highlight an extensive level of brain processing of emotional information
      related to body language, which relies mostly on body kinematics. 

PMID- 26220747
TI  - A cautionary note on using secondary phenotypes in neuroimaging genetic studies.
AB  - Almost all genome-wide association studies (GWASs), including Alzheimer's Disease
      Neuroimaging Initiative (ADNI), are based on the case-control study design,
      implying that the resulting case-control data are likely a biased, not random,
      sample of the target population. Although association analysis of the disease
      (e.g. Alzheimer's disease in the ADNI) can be conducted using a standard logistic
      regression by ignoring the biased case-control sampling, a standard linear
      regression analysis on a secondary phenotype (e.g. any neuroimaging phenotype in
      the ADNI) may in general lead to biased inference, including biased parameter
      estimates, inflated Type I errors and reduced power for association testing.
      Despite of this well known result in genetic epidemiology, to our surprise, all
      the published studies on secondary phenotypes with the ADNI data have ignored
      this potential problem. Here we aim to answer whether such a standard analysis of
      a secondary phenotype is valid or problematic with the ADNI data. Through both
      real data analyses and simulation studies, we found that, strikingly, such an
      analysis was generally valid (with only small biases or slightly inflated Type I
      errors) for the ADNI data, though cautions must be taken when analyzing other
      data. We also illustrate applications and possible problems of two methods
      specifically developed for valid analysis of secondary phenotypes. 

PMID- 26220748
TI  - Visual search in depth: The neural correlates of segmenting a display into
      relevant and irrelevant three-dimensional regions.
AB  - Visual perception is facilitated by the ability to selectively attend to relevant
      parts of the world and to ignore irrelevant regions or features. In visual search
      tasks, viewers are able to segment displays into relevant and irrelevant items
      based on a number of factors including the colour, motion, and temporal onset of
      the target and distractors. Understanding the process by which viewers prioritise
      relevant parts of a display can provide insights into the effect of top-down
      control on visual perception. Here, we investigate the behavioural and neural
      correlates of segmenting a display according to the expected three-dimensional
      (3D) location of a target. We ask whether this segmentation is based on low-level
      visual features (e.g. common depth or common surface) or on higher-order
      representations of 3D regions. Similar response-time benefits and neural activity
      were obtained when items fell on common surfaces or within depth-defined volumes,
      and when displays were vertical (such that items shared a common depth/disparity)
      or were tilted in depth. These similarities indicate that segmenting items
      according to their 3D location is based on attending to a 3D region, rather than
      a specific depth or surface. Segmenting the items in depth was mainly associated
      with increased activation in depth-sensitive parietal regions rather than in
      depth-sensitive visual regions. We conclude that segmenting items in depth is
      primarily achieved via higher-order, cue invariant representations rather than
      through filtering in lower-level perceptual regions. 

PMID- 26220750
TI  - Use of the methacetin breath test to classify the risk of cirrhotic complications
      and mortality in patients evaluated/listed for liver transplantation.
AB  - BACKGROUND & AIMS: The MELD score predicts short-term mortality in patients with
      cirrhosis; however, some patients with low scores develop complications and die
      unexpectedly. Consequently, we evaluated the diagnostic accuracy of the
      methacetin breath test (MBT), an assay of liver metabolic function, and the MELD
      score, to predict the risk of complications of cirrhosis and liver-related death.
      METHODS: One hundred sixty-five patients with cirrhosis received oral (13)C
      methacetin; (13)CO2 was measured in expired breath (BreathID; Exalenz). The
      cumulative percent dose recovery of (13)CO2 at 20 min with a threshold of ?0.55%
      (high-risk) and >0.55% (low risk) most accurately predicted liver-related death
      and the risk of cirrhotic complications within one year. MELD thresholds of ?15
      and ?19 were also examined to predict the same endpoints. RESULTS: Dose recovery
      ?0.55% and MELD ?19 both predicted liver-related death (HR 12.6 [95% CI 1.6
      98.3]; p=0.016, and HR 5.5 [1.6-18.9]; p=0.007, respectively); MELD ?15 did not.
      Dose recovery ?0.55% (HR 1.9 [1.1-3.2]; p=0.03) also predicted the risk of ?1
      complication(s), and was particularly able to foretell the risk of
      development/exacerbation of ascites (HR 4.7 [1.8-11.9]; p=0.001), which was not
      achieved by either MELD threshold. Finally, in patients with MELD <19, dose
      recovery ?0.55% predicted the risk of death (p=0.017), development of ?1
      cirrhotic complication(s) (p=0.062), and development/exacerbation of ascites
      (p=0.0009). CONCLUSIONS: In this pilot study, methacetin breath testing predicted
      the risk of liver-related death and development/exacerbation of ascites more
      accurately than MELD ?15 or ?19. In patients with low MELD (<19points), MBT may
      be useful to identify patients in whom the frequency of clinical observation
      should be intensified.

PMID- 26220749
TI  - A cell culture system for distinguishing hepatitis C viruses with and without
      liver cancer-related mutations in the viral core gene.
AB  - BACKGROUND & AIMS: Although patients infected by genotype 1b hepatitis C virus
      (HCV) with Q(70) and/or M(91)core gene mutations have an almost five-fold
      increased risk of developing hepatocellular carcinoma (HCC) and increased insulin
      resistance, the absence of a suitable experimental system has precluded direct
      experimentation on the effects of these mutations on cellular gene expression.
      METHODS: HuH7 cells were treated long-term with human serum to induce
      differentiation and to produce a model system for testing high-risk and control
      HCV. For clinical validation, profiles of infected cells were compared to each
      other and to those of liver biopsies of patients with early-stage HCV-related
      cirrhosis followed prospectively for up to 23 years (n=216). RESULTS: Long-term
      culture in human serum produced growth-arrested, hepatocyte-like cells whose gene
      profile overlapped significantly with that of primary human hepatocytes. High
      risk (Q(70)/M(91)) and control (R(70)/L(91)) viruses had dramatically different
      effects on gene expression of these cells. The high-risk virus enhanced
      expression of pathways associated with cancer and type II diabetes, while the
      control virus enhanced pathways associated with oxidative phosphorylation. Of
      special clinical relevance, the transcriptome of cells replicating the high-risk
      virus correlated significantly with an HCC high-risk profile in patients
      (Bonferroni-corrected p=0.03), whereas no such association was observed for non
      HCC-related clinical outcomes. CONCLUSIONS: The cell-based system allowed direct
      head-to-head comparison of HCV variants, and provided experimental support for
      previous clinical data indicating an oncogenic effect of core gene mutations.
      This simple experimental system distinguished HCV variants and will enable future
      mechanistic analysis and exploration of interventional approaches.

PMID- 26220751
TI  - Exposure to fine airborne particulate matters induces hepatic fibrosis in murine
      models.
AB  - BACKGROUND & AIMS: Hepatic fibrosis, featured by the accumulation of excessive
      extracellular matrix in liver tissue, is associated with metabolic disease and
      cancer. Inhalation exposure to airborne particulate matter in fine ranges (PM2.5)
      correlates with pulmonary dysfunction, cardiovascular disease, and metabolic
      syndrome. In this study, we investigated the effect and mechanism of PM2.5
      exposure on hepatic fibrogenesis. METHODS: Both inhalation exposure of mice and
      in vitro exposure of specialized cells to PM2.5 were performed to elucidate the
      effect of PM2.5 exposure on hepatic fibrosis. Histological examinations, gene
      expression analyses, and genetic animal models were utilized to determine the
      effect and mechanism by which PM2.5 exposure promotes hepatic fibrosis. RESULTS:
      Inhalation exposure to concentrated ambient PM2.5 induces hepatic fibrosis in
      mice under the normal chow or high-fat diet. Mice after PM2.5 exposure displayed
      increased expression of collagens in liver tissues. Exposure to PM2.5 led to
      activation of the transforming growth factor beta-SMAD3 signaling, suppression of
      peroxisome proliferator-activated receptor gamma, and expression of collagens in
      hepatic stellate cells. NADPH oxidase plays a critical role in PM2.5-induced
      liver fibrogenesis. CONCLUSIONS: Exposure to PM2.5 exerts discernible effects on
      promoting hepatic fibrogenesis. NADPH oxidase mediates the effects of PM2.5
      exposure on promoting hepatic fibrosis.

PMID- 26220753
TI  - Disruption of HNF1alpha binding site causes inherited severe unconjugated
      hyperbilirubinemia.
AB  - Crigler-Najjar syndrome presents as severe unconjugated hyperbilirubinemia and is
      characteristically caused by a mutation in the UGT1A1 gene, encoding the enzyme
      responsible for bilirubin glucuronidation. Here we present a patient with Crigler
      Najjar syndrome with a completely normal UGT1A1 coding region. Instead, a
      homozygous 3 nucleotide insertion in the UGT1A1 promoter was identified that
      interrupts the HNF1alpha binding site. This mutation results in almost complete
      abolishment of UGT1A1 promoter activity and prevents the induction of UGT1A1
      expression by the liver nuclear receptors CAR and PXR, explaining the lack of a
      phenobarbital response in this patient. Although animal studies have revealed the
      importance of HNF1alpha for normal liver function, this case provides the first
      clinical proof that mutations in its binding site indeed result in severe liver
      pathology stressing the importance of promoter sequence analysis. 

PMID- 26220752
TI  - Inflammatory regulation of steroid sulfatase: A novel mechanism to control
      estrogen homeostasis and inflammation in chronic liver disease.
AB  - BACKGROUND & AIMS: Chronic inflammatory liver diseases are associated with
      estrogen excess and feminization in men, which is thought to be due to
      compromised liver function to break down estrogens. The goal of this study is to
      determine whether the inflammatory induction of steroid sulfatase (STS), which
      converts inactive estrogen sulfates to active estrogens, may have contributed to
      the estrogen excess in chronic liver disease. METHODS: We performed bioinformatic
      analysis, real-time PCR, immunohistochemistry, and UPLC/MS-MS to analyze hepatic
      STS expression and serum estrogen levels in patients with chronic liver diseases.
      The crosstalk between NF-kappaB pathway and STS-regulated estrogen signaling was
      investigated by electrophoretic mobility shift assay, chromatin
      immunoprecipitation, luciferase assay and gene knockdown experiments in human
      hepatocytes. RESULTS: Hepatic STS was induced in patients with chronic
      inflammatory liver diseases, which was accompanied by increased circulating
      estrogen levels. The human STS gene, but not the mouse Sts gene, was induced by
      inflammatory stimuli in hepatic cells. Mechanistically, STS was established as a
      novel NF-kappaB target gene, whose induction facilitated the conversion of
      inactive estrogen sulfates to active estrogens, and consequently attenuated the
      inflammatory response. In contrast, genetic or pharmacological inhibition of STS
      or a direct blockade of estrogen signaling sensitized liver cells to the
      transcriptional activation of NF-kappaB and inflammatory response, possibly
      through the inhibition of IkappaB kinase activation. CONCLUSIONS: Our results
      suggest a negative feedback loop in chronic inflammatory liver diseases, in which
      the inflammatory activation of NF-kappaB induces STS gene expression. The induced
      STS facilitates the conversion of inactive estrogen sulfates to active estrogens,
      which in return attenuates the NF-kappaB-mediated inflammation.

PMID- 26220755
TI  - EASL Recognition Award Recipient 2015: Prof. Dominique C. Valla.

PMID- 26220754
TI  - Progenitor cell markers predict outcome of patients with hepatocellular carcinoma
      beyond Milan criteria undergoing liver transplantation.
AB  - BACKGROUND & AIMS: In patients with hepatocellular carcinoma (HCC), liver
      transplantation (LT) is an excellent therapy if tumor characteristics are within
      the Milan criteria. We aimed to define genomic features enabling to identify HCC
      patients beyond Milan criteria who have acceptable transplant outcomes. METHODS:
      Among 770 consecutive HCC patients transplanted between 1990 and 2013, 132 had
      tumors exceeding Milan criteria on pathology and were enrolled in the study; 44%
      of the patients satisfied the 'up-to-7 rule' [7=sum of the size of the largest
      tumor and the number of tumors]. Explant tumors were assessed for genomic
      signatures and immunohistochemical markers associated with poor outcome. RESULTS:
      At a median follow-up of 88months, 64 patients had died and 45 recurred; the 5
      year overall survival (OS) and recurrence rates were 57% and 35%, respectively.
      Cytokeratin 19 (CK19) gene signature was independently associated with recurrence
      [Hazard ratio (HR)=2.95, p<0.001], along with tumor size (HR=3.37, p=0.023) and
      presence of satellites (HR=2.98, p=0.001). S2 subclass signature was
      independently associated with poor OS (HR=3.18, p=0.001), along with tumor size
      (HR=5.06, p<0.001) and up-to-7 rule (HR=2.50, p=0.002). Using the presence of
      progenitor cell markers (either CK19 or S2 signatures) patients were classified
      into poor prognosis (n=58; 5-year recurrence 53%, survival 45%) and good
      prognosis (n=74; 5-year recurrence 19%, survival 67%) (HR=3.16, p<0.001 for
      recurrence, and HR=1.72, p=0.04 for OS). CONCLUSIONS: HCC patients transplanted
      beyond Milan criteria without gene signatures of progenitor markers (CK19 and S2)
      achieved survival rates similar as those within Milan criteria. Once
      prospectively validated, these markers may support a limited expansion of LT
      indications.

PMID- 26220756
TI  - Timing of diffusion tensor imaging in the acute spinal cord injury of rats.
AB  - The aim of this study was to evaluate the characteristics of magnetic resonance
      diffusion tensor imaging (DTI) in acute spinal cord following a thoracic spinal
      cord injury (SCI), and to determine the optimal time of examination. Sprague
      Dawley rats were used as experimental animals and contusion injuries were made at
      the T10 vertebral level. The rats were divided into control, mild injury,
      moderate injury, and severe injury groups. Spinal magnetic resonance DTI was
      scheduled at 6, 24 and 72 hours (h) post-SCI, and the DTI parameters such as
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were
      calculated, and the diffusion tensor tractography (DTT) of the spinal cord was
      also generated. We observed a significant decrease of FA in all the three injured
      groups, and the FA at 24 h post-SCI exhibited the greatest decrease among
      different set times. For ADC, only the group of severely injured rats saw a
      significant decrease at 24 and 72 h compared with the control group. DTT showed
      interruption of nerve fiber tracking in the injured groups. This study
      demonstrates that FA can differentiate various grades of SCI in the early stage,
      and 24 h after injury might be the optimal time for identifying injury severity. 

PMID- 26220758
TI  - [Comments on: Influence of lay person resuscitation on the 30-day survival rate].

PMID- 26220757
TI  - Secular trends in age at menarche among Chinese girls from 24 ethnic minorities,
      1985 to 2010.
AB  - BACKGROUND: Declining age at menarche has been observed in many countries. In
      China, a decrease of 4.5 months per decade in the average age at menarche among
      the majority Han girls has recently been reported. However, the trends in age at
      menarche among ethnic minority girls over the past 25 years remain unknown.
      OBJECTIVES: To compare the differences in median age at menarche among girls aged
      9-18 years across 24 ethnic minorities in 2010 and to estimate the trends in age
      at menarche in different ethnic minorities from 1985 to 2010. DESIGN: We used
      data from six cross-sectional Chinese National Surveys on Students' Constitution
      and Health (1985, 1991, 1995, 2000, 2005, and 2010). The median age at menarche
      was estimated by using probit analysis. RESULTS: In 2010, the ethnic minorities
      with the earliest age at menarche were the Koreans (11.79 years), Mongolians
      (12.44 years), and Zhuang (12.52 years). The three ethnic minorities with the
      latest age at menarche were the Sala (14.32 years), Yi (13.74 years), and Uighurs
      (13.67 years). From 1985 to 2010, the age at menarche declined in all 24 minority
      groups. The Lisu, Kazakh, and Korean minorities showed the largest reductions in
      age at menarche by 1.79 (p<0.05), 1.69 (p<0.05), and 1.57 (p<0.05) years,
      respectively, from 1985 to 2010. The Yi, Sala, and Li minorities showed the
      smallest reductions, with age at menarche declining by only 0.06 (p>0.05), 0.15
      (p>0.05), and 0.15 (p>0.05) years, respectively, in the same period. CONCLUSION:
      A large variation in age at menarche was observed among different ethnic
      minorities, with the earliest age at menarche found among Korean girls. A
      reduction in the average age at menarche appeared among most of the ethnic
      minorities over time, and the largest decrease was observed in Lisu, Kazakh, and
      Korean girls. Thus, health education should focus on targeting the specific needs
      of each ethnic minority group.

PMID- 26220759
TI  - Pretransplantation use of the second-generation tyrosine kinase inhibitors has no
      negative impact on the HCT outcome.
AB  - INTRODUCTION: Allogeneic hematopoietic cell transplantation (HCT) was a standard
      therapy in chronic phase (CP) chronic myeloid leukemia (CML). As a result of the
      effective therapy with tyrosine kinase inhibitors (TKI), HCT was shifted to
      defined clinical situations. We present the results of observational prospective
      analysis of 28 CML patients undergoing HCT after exposure to, at least, two lines
      of TKI (including dasatinib and/or nilotinib), with respect to response, overall
      survival (OS), treatment toxicity, graft versus host disease (GVHD), and
      progression/relapse incidence. RESULTS: All the patients but one engrafted with
      median time 19 days. OS for patients in CP1 and CP2/accelerated phase (AcP) were
      92.9 and 85.7 %, respectively. Six patients allotransplanted in blast crisis (BC)
      CML died early after HCT. Eighteen patients achieved deep molecular remission
      (MR(4.5) or MR(4.0)). Relapse incidence was 29.6 %. Median time to progression
      (TTP) differs significantly depending on the CML phase prior to HCT, the best
      response achieved after HCT and development of chronic GvHD. NRM yielded the
      values 7.1, 12.5, and 50 % in CP1, CP2/AcP, and BC, respectively. Fatal outcome,
      due to veno-occlusive disease (VOD), was observed in two (7 %) patients. In five
      (17.9 %) patients, mild or moderate VOD was observed with no negative impact of
      preceding therapy with TKI2. Acute GvHD was diagnosed in 25.9 % of patients,
      while chronic GvHD developed in 42.9 % of individuals. CONCLUSION:
      Pretransplantation therapy with TKI2 in CP CML is safe and reasonable. In BC, the
      optimal approach before HCT is to reduce the leukemic burden and achieve
      subsequent CP.

PMID- 26220762
TI  - Alfaxalone versus alfaxalone-dexmedetomidine anaesthesia by immersion in oriental
      fire-bellied toads (Bombina orientalis).
AB  - OBJECTIVE: To determine a dexmedetomidine concentration, to be added to an
      alfaxalone-based bath solution, that will enhance the anaesthetic and analgesic
      effects of alfaxalone; and to compare the quality of anaesthesia and analgesia
      provided by immersion with either alfaxalone alone or alfaxalone with
      dexmedetomidine in oriental fire-bellied toads (Bombina orientalis). STUDY
      DESIGN: Pilot study followed by a prospective, randomized, experimental trial.
      ANIMALS: Fourteen oriental fire-bellied toads. METHODS: The pilot study aimed to
      identify a useful dexmedetomidine concentration to be added to an anaesthetic
      bath containing 20 mg 100 mL(-1) alfaxalone. Thereafter, the toads were assigned
      to one of two groups, each comprising eight animals, to be administered either
      alfaxalone (group A) or alfaxalone-dexmedetomidine (group AD). After immersion
      for 20 minutes, the toads were removed from the anaesthetic bath and the
      righting, myotactic and nociceptive reflexes, cardiopulmonary variables and von
      Frey filaments threshold were measured at 5 minute intervals and compared
      statistically between groups. Side effects and complications were noted and
      recorded. RESULTS: In the pilot study, a dexmedetomidine concentration of 0.3 mg
      100 mL(-1) added to the alfaxalone-based solution resulted in surgical
      anaesthesia. The toads in group AD showed higher von Frey thresholds and lower
      nociceptive withdrawal reflex scores than those in group A. However, in group AD,
      surgical anaesthesia was observed in two out of eight toads only, and induction
      of anaesthesia was achieved in only 50% of the animals, as compared with 100% of
      the toads in group A. CONCLUSIONS AND CLINICAL RELEVANCE: The addition of
      dexmedetomidine to an alfaxalone-based solution for immersion anaesthesia
      provided some analgesia in oriental fire-bellied toads, but failed to potentiate
      the level of unconsciousness and appeared to lighten the depth of anaesthesia.
      This limitation renders the combination unsuitable for anaesthetizing oriental
      fire-bellied toads for invasive procedures.

PMID- 26220760
TI  - The temporary and accumulated effects of transcranial direct current stimulation
      for the treatment of advanced Parkinson's disease monkeys.
AB  - Transcranial direct current stimulation (tDCS) is a useful noninvasive technique
      of cortical brain stimulation for the treatment of neurological disorders.
      Clinical research has demonstrated tDCS with anodal stimulation of primary motor
      cortex (M1) in Parkinson's disease (PD) patients significantly improved their
      motor function. However, few studies have been focused on the optimization of
      parameters which contributed significantly to the treatment effects of tDCS and
      exploration of the underline neuronal mechanisms. Here, we used different
      stimulation parameters of anodal tDCS on M1 for the treatment of aged advanced PD
      monkeys induced with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)
      administration, and then analyzed the temporary and accumulated effects of tDCS
      treatment. The results indicated anodal tDCS on M1 very significantly improved
      motor ability temporarily; importantly, the treatment effects of anodal tDCS on
      M1 were quantitatively correlated to the accumulated stimulation instead of the
      stimuli intensity or duration respectively. In addition, c-fos staining showed
      tDCS treatment effects activated the neurons both in M1 and substantia nigra
      (SN). Therefore, we propose that long time and continue anodal tDCS on M1 is a
      better strategy to improve the motor symptoms of PD than individual manipulation
      of stimuli intensity or duration. 

PMID- 26220763
TI  - Probiotics and growth in preterm infants: A randomized controlled trial, PREMAPRO
      study.
AB  - BACKGROUND & AIMS: Recent studies have suggested that the gut microflora has
      metabolic effects. We aimed to evaluate postnatal growth in preterm infants who
      received different probiotic supplements, and to assess the safety of probiotic
      administration. METHODS: This prospective, randomized, double-blind, controlled
      trial was performed at three tertiary care neonatal units. Preterm infants were
      randomly assigned to receive daily supplementation over 4-6 weeks with placebo
      (group C) or probiotics (group P). Group P comprised three subgroups: P1 received
      Bifidobacterium lactis, P2 received Bifidobacterium longum, and P3 received B.
      lactis and B. longum. We assessed postnatal growth during the supplementation
      period and up to a corrected gestational age (GA) of 41 weeks when body
      composition was assessed using whole-body dual-energy X-ray absorptiometry.
      Aerobic and anaerobic blood cultures were performed on suspicion of late-onset
      sepsis. RESULTS: The study comprised 199 preterm infants with a mean GA of 29.1
      +/- 1.4 weeks and a mean birth weight of 1173 +/- 210 g, who received a placebo
      (group C, n = 52) or probiotics (group P, n = 147) from the first week of life.
      At the end of the supplementation period, no statistically significant
      differences were seen between the groups in relation to the mean body weight
      (group C = 1906 +/- 23 g, group P = 1875 +/- 14 g, p = 0.25), length, or head
      circumference. The incidence rates of necrotizing enterocolitis and late-onset
      sepsis were similar in the two groups. At the corrected GA of 41 weeks, there
      were no differences between the groups with respect to anthropometric
      measurements or body composition analysis. CONCLUSIONS: Preterm infants receiving
      Bifidobacterium supplements did not exhibit better postnatal growth compared with
      those who received placebo treatment. No adverse effects were associated with
      probiotic administration. Registered under ClinicalTrials.gov Identifier no.
      NCT01379417.

PMID- 26220764
TI  - Prognostic value of CA 19-9 kinetics during gemcitabine-based chemotherapy in
      patients with advanced cholangiocarcinoma.
AB  - BACKGROUND: Little is known of the prognostic value of CEA/CA 19-9 kinetics
      during chemotherapy in patients with advanced cholangiocarcinoma (CCA). METHODS:
      A total of 236 patients with pathologically confirmed advanced CCA received
      gemcitabine-based chemotherapy were reviewed, and 179 were eligible for analysis.
      Baseline, pre-, and post-treatment (after two cycles of chemotherapy) CEA and CA
      19-9 values were checked, and survival was compared according to various cutting
      points of baseline measurement or extent of change of tumor marker level.
      RESULTS: Patients with a >= 50% decline in CA 19-9 level had better survival than
      the others (16.0 vs 9.0 months). However, CEA decline did not predict survival
      gain. Significant favorable prognostic factors of survival in multivariable
      analysis included initial treatment response (HR 0.61), distal location of tumor
      (HR 0.46), baseline CA 19-9 level <= 1000 U/mL (HR 0.58), and >= 50% decline in
      CA 19-9 level (HR 0.50). Subgroup analysis was conducted in 114 patients with pre
      treatment CA 19-9 > 37 U/mL and bilirubin <= 2 mg/dL. Decline >= 50% in CA 19-9
      level still showed an independent prognostic significance (HR 0.45). CONCLUSION:
      CA 19-9 but not CEA kinetics serves as a predictor of better survival in patients
      with advanced CCA on gemcitabine-based chemotherapy. A >= 50% decline in CA 19-9
      level after two cycles of chemotherapy may have clinical utility as an early
      indicator of better response to gemcitabine-based chemotherapy.

PMID- 26220765
TI  - Low 25-hydroxyvitamin D, but not the bioavailable fraction of 25-hydroxyvitamin
      D, is a risk factor for multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Low 25-hydroxyvitamin D [25(OH)D] levels correlate with
      higher disease activity in patients with multiple sclerosis (MS). However, it is
      not clear whether low 25(OH)D levels directly contribute to increased disease
      activity or merely represent a consequence of reduced endogenous vitamin D
      synthesis in more disabled MS patients. Furthermore, recent data suggest that
      bioavailable vitamin D, which also integrates the levels of vitamin D binding
      proteins and albumin, could be a biologically more relevant parameter than
      25(OH)D. METHODS: Measured de-seasonalized 25(OH)D3 and vitamin D binding protein
      and calculated bioavailable and free vitamin D were compared in the baseline
      serum samples of 76 patients with clinically isolated syndrome enrolled in a
      longitudinal observational study and in 76 age- and sex-matched healthy controls
      (HC). RESULTS: 25(OH)D3 levels were lower in patients with clinically isolated
      syndrome (P = 0.002) than in HC, and more patients (8/76, 10.5%) than HC (1/76,
      1.3%) had 25(OH)D3 levels <25 nmol/l (P = 0.03). In contrast, levels of 25(OH)D2,
      vitamin D binding protein and calculated levels of free and bioavailable vitamin
      D did not differ between the two groups. CONCLUSIONS: Lower 25(OH)D3 levels
      already in the earliest phase of disease and in clinically hardly affected
      patients suggest that low 25(OH)D3 levels are rather a risk factor for than a
      consequence of MS. Nevertheless, because bioavailable vitamin D levels did not
      differ between the two groups, the mechanism underlying the association of
      25(OH)D3 and MS does not appear to be related to reduced bioavailability of
      vitamin D.

PMID- 26220766
TI  - Screening and Brief Interventions for Alcohol and Other Drug Use Among Pregnant
      Women Attending Midwife Obstetric Units in Cape Town, South Africa: A Qualitative
      Study of the Views of Health Care Professionals.
AB  - INTRODUCTION: Despite the negative consequences of alcohol and other drug use
      during pregnancy, few interventions for pregnant women are implemented, and
      little is known about their feasibility and acceptability in primary health care
      settings in South Africa. As part of the formative phase of screening, brief
      intervention, and referral to treatment for substance use among women presenting
      for antenatal care, the present study explored health care workers' attitudes and
      perceptions about screening, brief intervention, and referral to treatment among
      this population. METHODS: Forty-three health care providers at 2 public sector
      midwife obstetric units in Cape Town, South Africa, were interviewed using an
      open-ended, semistructured interview schedule designed to identify factors that
      hinder or support the implementation of screening, brief intervention, and
      referral to treatment for substance use in these settings. Transcribed interviews
      were analyzed using the framework approach. RESULTS: Health care providers agreed
      that there is a substantial need for screening, brief intervention, and referral
      to treatment for substance use among pregnant women and believe such services
      potentially could be integrated into routine care. Several women-, staff-, and
      clinic-level barriers were identified that could hinder the successful
      implementation in antenatal services. These barriers included the nondisclosure
      of alcohol and other drug use, the intervention being considered as an add-on
      service or additional work, negative staff attitudes toward implementation of an
      intervention, poor staff communication styles such as berating women for their
      behavior, lack of interest from staff, time constraints, staff shortages,
      overburdened workloads, and language barriers. DISCUSSION: The utility of
      screening, brief intervention, and referral to treatment for addressing substance
      use among pregnant women in public health midwife obstetric units was supported,
      but consideration will need to be given to addressing a variety of barriers that
      have been identified.

PMID- 26220767
TI  - 17beta-Estradiol inhibits vascular smooth muscle cell migration via up-regulation
      of striatin protein.
AB  - Striatin, an estrogen receptor (ER)-interacting protein, plays an important role
      in estrogen's nongenomic actions in vascular endothelial cells. However, the role
      of striatin in VSMCs is unknown. Here, we investigated the role of striatin in
      estrogen-regulated VSMCs migration. 17beta-Estradiol (E2) at 10 nM largely
      inhibited VSMCs migration, which was reversed by the silencing of striatin
      expression. E2 increased striatin protein expression in a dose- and time
      dependent manner. ERalpha agonist PPT, but not ERbeta agonist DPN, mimicked the
      regulatory effect of E2. The regulatory effect of E2 on striatin protein
      expression was blocked by the pure ER antagonist ICI 182,780 or the mitogen
      activated protein kinase inhibitor PD98059, but not by the phosphatidylinositol-3
      kinase inhibitor wortmannin or Src inhibitor PP2, suggesting that E2 increased
      striatin protein expression via extracellular-signal regulated kinase 1/2
      (ERK1/2). E2 resulted in phosphorylation of ERK1/2 in a time-dependent manner.
      The silencing of ERK1/2 largely abolished E2-enhanced striatin expression.
      Finally, the inhibitory effect of E2 on VSMC migration was reversed by ICI
      182,780 or PD98059. Taken together, our results indicate that E2 inhibits VSMC
      migration by increasing striatin expression via ERalpha to ERK1/2 pathway, which
      maybe helpful to understand estrogen's anti-atherogenic effect in VSMCs. 

PMID- 26220768
TI  - Elevated thrombin activatable fibrinolysis inhibitor levels in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: The aim of the present study was to evaluate plasma concentrations of
      thrombin activatable fibrinolysis inhibitor (TAFI) in relation with hormonal,
      metabolic, and hemostatic profile in patients with and without polycystic ovary
      syndrome (PCOS). STUDY DESIGN: A total of 38 women with PCOS and 37 age and body
      mass index (BMI) matched controls were eligible for the study. Hirsutism scores,
      hormonal, metabolic, and hemostatic profile as well as TAFI levels were evaluated
      in each subject. RESULTS: Women with PCOS exhibited higher plasma concentrations
      of TAFI levels than controls (107.42 +/- 34.77% versus 91.86 +/- 23.88%, p =
      0.027). TAFI levels were significantly correlated positively with BMI, fasting
      insulin levels, modified Ferriman Gallwey scores and Homeostasis Model Assessment
      (HOMA) index, systolic blood pressure, and waist and hip circumferences, whereas
      negatively correlated with activated partial thromboplastin time (p < 0.05).
      However, after adjustment for all possible confounding factors, none of the
      parameters was significantly deterministic on TAFI levels. CONCLUSION: The data
      of the present study suggested that plasma TAFI levels were higher in women with
      PCOS as compared with healthy age and BMI-matched controls, indicating impaired
      fibrinolysis. This hypofibrinolytic state may be responsible for the increased
      cardiovascular disease risk in women with PCOS.

PMID- 26220769
TI  - The adipokine leptin mediates muscle- and liver-derived IGF-1 in aged mice.
AB  - Muscle- and liver-derived IGF-1 play important roles in muscle anabolism
      throughout growth and aging. Yet, prolonged food restriction is thought to
      increase longevity in part by lowering levels of IGF-1, which in turn reduces the
      risk for developing various cancers. The dietary factors that modulate IGF-1
      levels are, however, poorly understood. We tested the hypothesis that the
      adipokine leptin, which is elevated with food intake and suppressed during
      fasting, is a key mediator of IGF-1 levels with aging and food restriction.
      First, leptin levels in peripheral tissues were measured in young mice fed ad
      libitum, aged mice fed ad libitum, and aged calorie-restricted (CR) mice. A group
      of aged CR mice were also treated with recombinant leptin for 10 days. Later,
      aged mice fed ad libitum were treated with saline (VEH) or with a novel leptin
      receptor antagonist peptide (Allo-aca) and tissue-specific levels of IGF-1 were
      determined. On one hand, recombinant leptin induced a three-fold increase in
      liver-derived IGF-1 and a two-fold increase in muscle-derived IGF-1 in aged, CR
      mice. Leptin also significantly increased serum growth hormone levels in the
      aged, CR mice. On the other, the leptin receptor antagonist Allo-aca did not
      alter body weight or muscle mass in treated mice compared to VEH mice. Allo-aca
      did, however, produce a significant (20%) decline in liver-derived IGF-1 as well
      as an even more pronounced (>50%) decrease in muscle-derived IGF-1 compared to
      VEH-treated mice. The reduced IGF-1 levels in Allo-aca treated mice were not
      accompanied by any significant change in growth hormone levels compared to VEH
      mice. These findings suggest that leptin receptor antagonists may represent novel
      therapeutic agents for attenuating IGF-1 signaling associated with aging, and
      could potentially mimic some of the positive effects of calorie restriction on
      longevity.

PMID- 26220770
TI  - Inhibition of Breast Cancer Metastasis by Pluronic Copolymers with Moderate
      Hydrophilic-Lipophilic Balance.
AB  - Metastasis is the primary cause resulting in the high mortality of breast cancer.
      The inherent antimetastasis bioactivity of Pluronic copolymers with a wide range
      of hydrophilic-lipophilic balance (HLB) including Pluronic L61, P85, P123, F127,
      F68, and F108 was first explored on metastatic 4T1 breast cancer cells. The
      results indicated that P85 and P123 could strongly inhibit the migration and
      invasion of 4T1 cells. The effects of the polymers on cell healing, migration,
      and invasion exhibited bell-shaped dependencies on HLB of Pluronic copolymers,
      and the better antimetastasis effects of Pluronic copolymers could be achieved
      with the HLB between 8 and 16. P85 and P123 themselves could significantly
      inhibit pulmonary metastasis in 4T1 mammary tumor metastasis model in situ. In
      addition, a synergetic antimetastasis effect could be achieved during drug
      combination of doxorubicin hydrochloride (DOX) and P85 or P123 intravenously. The
      metastasis effects of P85 and P123 both in vitro and in vivo were partially
      attributed to the downregulation of matrix metalloproteinase-9 (MMP-9).
      Therefore, Pluronic copolymers with moderate HLB 8-16 such as P85 and P123 could
      be promising excipients with therapeutics in drug delivery systems to inhibit
      breast cancer metastasis. 

PMID- 26220771
TI  - The Nucleation of Semantic Information in Prebiotic Matter.
AB  - The analysis of the inherent context-dependence of genetic information suggests
      that there are evolutionary mechanisms which are independent of the processes of
      environmental adaptation and yet are able to push prebiotic matter towards
      functional complexity. In this regard, the extension of information space, by
      random prolongation of the primary structure of biological macromolecules, must
      have played a decisive role in the origin of life. On the one hand, the extension
      of information space is tantamount to an increase in the syntactic complexity of
      potential information carriers, which in turn is a prerequisite for the
      nucleation and evolution of semantic information. On the other hand, the increase
      in the dimensionality of information space expands the number of possible
      pathways of evolutionary optimisation and thereby improves the possible choices
      that can be made by progressive evolution. Alongside the optimisation of
      evolutionary optimisation itself, there are principles of evolutionary dynamics
      that direct the formation of functional order in prebiotic matter. Since these
      principles are constitutive for the proto-semantics of genetic information, they
      may be regarded as the elements of the semantic code of evolution. 

PMID- 26220773
TI  - Detecting anthropogenic footprints in sea level rise.
AB  - While there is scientific consensus that global and local mean sea level (GMSL
      and LMSL) has risen since the late nineteenth century, the relative contribution
      of natural and anthropogenic forcing remains unclear. Here we provide a
      probabilistic upper range of long-term persistent natural GMSL/LMSL variability
      (P=0.99), which in turn, determines the minimum/maximum anthropogenic
      contribution since 1900. To account for different spectral characteristics of
      various contributing processes, we separate LMSL into two components: a slowly
      varying volumetric component and a more rapidly changing atmospheric component.
      We find that the persistence of slow natural volumetric changes is underestimated
      in records where transient atmospheric processes dominate the spectrum. This
      leads to a local underestimation of possible natural trends of up to ~1 mm per
      year erroneously enhancing the significance of anthropogenic footprints. The
      GMSL, however, remains unaffected by such biases. On the basis of a model
      assessment of the separate components, we conclude that it is virtually certain
      (P=0.99) that at least 45% of the observed increase in GMSL is of anthropogenic
      origin. 

PMID- 26220772
TI  - Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular
      Disease.
AB  - The long non-coding RNA CDKN2B-AS1, commonly referred to as the A ntisense N on
      coding R NA in the I NK4 L ocus (ANRIL), is a 3.8-kb-long RNA transcribed from
      the short arm of human chromosome 9 on p21.3 that overlaps a critical region
      encompassing three major tumor suppressor loci juxtaposed to the INK4b-ARF-INK4a
      gene cluster and the methyl-thioadenosine phosphorylase (MTAP) gene. Genome-wide
      association studies have identified this region with a remarkable and growing
      number of disease-associated DNA alterations and single nucleotide polymorphisms,
      which corresponds to increased susceptibility to human disease. Recent attention
      has been devoted on whether these alterations in the ANRIL sequence affect its
      expression levels and/or its splicing transcript variation, and in consequence,
      global cellular homeostasis. Moreover, recent evidence postulates that ANRIL not
      only can regulate their immediate genomic neighbors in cis, but also has the
      capacity to regulate additional loci in trans. This action would further increase
      the complexity for mechanisms imposed through ANRIL and furthering the scope of
      this lncRNA in disease pathogenesis. In this chapter, we summarize the most
      recent findings on the investigation of ANRIL and provide a perspective on the
      biological and clinical significance of ANRIL as a putative biomarker,
      specifically, its potential role in directing cellular fates leading to cancer
      and cardiovascular disease. 

PMID- 26220774
TI  - Assessing the clinical features of LGI1 antibody encephalitis.

PMID- 26220775
TI  - Correlating high power conversion efficiency of PTB7:PC71BM inverted organic
      solar cells with nanoscale structures.
AB  - Advances in material design and device engineering led to inverted organic solar
      cells (i-OSCs) with superior power conversion efficiencies (PCEs) compared to
      their "conventional" counterparts, in addition to the well-known better ambient
      stability. Here, we report an in-depth morphology study of the i-OSC active and
      cathode modifying layers, employing a model system with a well-established bulk
      heterojunction, PTB7:PC71BM as the active layer and poly-[(9,9-bis(3'-(N,N
      dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)] (PFN) as the
      cathode surface modifying layer. We have also identified the role of a processing
      additive, 1,8-diiodooctane (DIO), used in the spin-casting of the active layer to
      increase PCE. Using various characterization techniques, we demonstrate that the
      high PCEs of i-OSCs are due to the diffusion of electron-accepting PC71BM into
      the PFN layer, resulting in improved electron transport. The diffusion occurs
      when residual solvent molecules in the spun-cast film act as a plasticizer.
      Addition of DIO to the casting solution results in more PC71BM diffusion and
      therefore more efficient electron transport. This work provides important insight
      and guidance to further enhancement of i-OSC performance by materials and
      interface engineering. 

PMID- 26220776
TI  - Polymerization stress--is it clinically meaningful?
AB  - OBJECTIVES: The objective of this article is to discuss the evidence for
      polymerization shrinkage and shrinkage stress of dental composite restoratives in
      terms of its potential relevance to the clinical situation METHODS: Articles
      relating to the issue of polymerization contraction stress generation in dental
      composite materials, and the factors that influence it, were reviewed and
      included. Particular attention was paid to evidence derived from clinical
      studies. Articles were identified through PubMed and through the bibliographies
      of other articles. RESULTS: There is extensive evidence for the presence of
      polymerization contraction stress in dental composites, as well as evidence for
      its deleterious effects, which include marginal leakage, gap formation, cuspal
      deflection, tooth cracking, reduced bond strength and lowered mechanical
      properties of the restorative. There is little, if any, direct evidence for the
      clinical effect of these contraction stresses. No study has directly established
      a link between these stresses and enhanced postoperative sensitivity or recurrent
      caries, for example. However, the concern over these stresses and the manner in
      which they influence the placement of current composite materials demonstrates
      that they are considered to be very important. CONCLUSION: Though no direct
      evidence exists to prove that the generation of contraction stress in dental
      composite restorations causes reduced clinical longevity, the indirect evidence
      from numerous in vitro studies and the concern over controlling their effects
      proves that they are clinically relevant.

PMID- 26220777
TI  - Resin-based composites show similar kinetic profiles for dimensional change and
      recovery with solvent storage.
AB  - OBJECTIVES: To investigate the sorption, solubility, mass change and hygroscopic
      expansion (solvent swelling) of resin-composites after long term storage in
      different solvents. METHODS: Eight materials were studied: two bulk-fill flowable
      materials (SDR and Venus bulk fill, V-BF), a packable bulk-fill material (Tetric
      Evoceram bulk-fill, TET-BF), a fiber reinforced material (Ever X posterior, EVX),
      a nano-hybrid conventional material (Tetric Evoceram, TET) and micro-hybrid
      conventional materials (G-aenial anterior, GA-P and posterior, GA-A). Three
      groups of disk shaped specimens were prepared using split stainless steel molds.
      Each group was stored, respectively, in: water, 75% ethanol/water and methyl
      ethyl ketone (MEK). The total storage time was 180 d plus a reconditioning time
      of 120 d. A non-contact laser scanning micrometer was used to measure the
      diametral changes. RESULTS: Significant differences were found in the sorption
      and solubility of the materials. Generally, MEK stored specimens had the highest
      values followed by 75% ethanol/water then water. A similar trend was found with
      the mass and volume changes (except for EVX). V-BF showed the highest sorption
      (98.1MUg/mm(3)) and solubility (10MUg/mm(3)) after MEK storage. Mass and volume
      changes showed near-linear correlation, with high Pearson coefficients (0.86
      0.99). SIGNIFICANCE: Generally the materials were most greatly affected by MEK
      storage compared to the other two solvents. The glass-fiber-reinforced EVX,
      however, was most affected by water immersion. The pattern of change/recovery
      behavior of the materials, during solvent challenge, was similar to the pattern
      of viscoelastic creep/recovery behavior of resin-composite materials.

PMID- 26220778
TI  - Compliance with Australian stroke guideline recommendations for outdoor mobility
      and transport training by post-inpatient rehabilitation services: An
      observational cohort study.
AB  - BACKGROUND: Community participation is often restricted after stroke, due to
      reduced confidence and outdoor mobility. Australian clinical guidelines recommend
      that specific evidence-based interventions be delivered to target these
      restrictions, such as multiple escorted outdoor journeys. The aim of this study
      was to describe post-inpatient outdoor mobility and transport training delivered
      to stroke survivors in New South Wales, Australia and whether therapy differed
      according to type, sector or location of service provider. METHODS: Using an
      observational retrospective cohort study design, 24 rehabilitation service
      providers were audited. Provider types included outpatient (n = 8), day therapy
      (n = 9), home-based rehabilitation (n = 5) and transitional aged care services
      (TAC, n = 2). Records of 15 stroke survivors who had received post-hospital
      rehabilitation were audited per service, for wait time, duration, amount of
      therapy and outdoor-related therapy. RESULTS: A total of 311 records were
      audited. Median wait time for post-hospital therapy was 13 days (IQR, 5-35).
      Median duration of therapy was 68 days (IQR, 35-109), consisting of 11 sessions
      (IQR 4-19). Overall, a median of one session (IQR 0-3) was conducted outdoors per
      person. Outdoor-related therapy was similar across service providers, except that
      TAC delivered an average of 5.4 more outdoor-related sessions (95% CI 4.4 to
      6.4), and 3.5 more outings into public streets (95% CI 2.8 to 4.3) per person,
      compared to outpatient services. CONCLUSION: The majority of service providers in
      the sample delivered little evidence-based outdoor mobility and travel training
      per stroke participant, as recommended in national stroke guidelines. TRIAL
      REGISTRATION: Australian and New Zealand Clinical Trials Registry
      ACTRN12611000554965.

PMID- 26220779
TI  - Polyaromatic hydrocarbons and elements in sediments associated with a suburban
      railway.
AB  - Railroad operations are a potential source for contamination of aquatic
      ecosystems. We examined concentrations of polyaromatic hydrocarbons (PAHs) and
      selected elements in sediments collected during 2009-2011 from streams, ditches,
      or ponds bisected or bordered by the former Elgin, Joliet, and Eastern rail line
      in the western Chicago, Illinois, metropolitan area. Summed PAH concentrations
      were greater in sediments collected downstream than in those collected upstream
      of the railroad and were negatively associated with distance within 500 m of the
      tracks. Phenanthrene and dibenzo (a,h)anthracene concentrations at some locations
      exceeded probable effect thresholds for risks to aquatic life. Although maximum
      levels of chromium (Cr) were below levels of concern, we did not determine the
      valence state of Cr; thus, risks to aquatic life could not be fully evaluated.
      Nickel and mercury concentrations exceeded lower effect levels, and vanadium
      concentrations exceeded chronic toxicity thresholds at some locations, although
      we did not detect an association between these elements and the presence of the
      railroad. Lead and arsenic concentrations were greater in proximity to the
      railroad; however, concentrations were below thresholds of concern for aquatic
      life. Our results suggest that the railroad and associated activities are
      contributing some environmental contaminants to waterways in close proximity to
      it, particularly in a downstream direction. Risks to aquatic life may be greater
      than implied by observed concentrations of individual contaminants, as
      synergistic adverse effects are likely to occur with exposure to complex
      mixtures. 

PMID- 26220780
TI  - Manure removal system influences the abundance and composition of airborne biotic
      contaminants in swine confinement buildings.
AB  - Little is known about the factors influencing the abundance and community
      composition of airborne biotic contaminants in swine confinement buildings
      (SCBs). Microbial air samples were collected from three different SCBs equipped
      with three different types of manure removal systems (deep-pit manure removal
      with slats, scraper removal system, and deep-litter bed system). The abundance
      and composition of airborne biotic contaminants of all the collected air samples
      were analyzed using cultivation-independent methods. The V1-V3 region of the 16S
      rRNA gene was amplified from the extracted DNA and sequenced using 454
      pyrosequencing. The abundances of 16S rRNA genes and six tetracycline resistance
      genes (tetB, tetH, tetZ, tetO, tetQ, and tetW) were quantified using real-time
      PCR. The abundance of 16S rRNA gene and tetracycline resistance genes were
      significantly higher in SCBs equipped with a deep-pit manure removal system with
      slats, except for tetB gene. This contrasts with the opposite trend found
      previously by culture-based studies. The aerial bacterial community composition,
      as measured by pairwise Bray-Curtis distances, varied significantly according to
      the manure removal system. 16S rRNA-based pyrosequencing revealed Firmicutes
      (72.4%) as the dominant group with Lactobacillus as the major genus, while
      Actinobacteria constituted 10.7% of the detectable bacteria. Firmicutes were more
      abundant in SCBs with deep pit with slats, whereas Actinobacteria were highly
      abundant in SCBs with a deep-litter bed system. Overall, the results of this
      study suggest that the manure removal system plays a key role in structuring the
      abundance and composition of airborne biotic contaminants in SCBs.

PMID- 26220781
TI  - Determination of metals in Brazilian soils by inductively coupled plasma mass
      spectrometry.
AB  - The concentration of metals in Brazilian soil under no-tillage (NT) and an area
      under native vegetation (NV) was determined by inductively coupled plasma mass
      spectrometry. The applied method was based on microwave-assisted acid digestion
      using HNO3, HCl, H2O2, and HF. The accuracy of the method was evaluated by
      analyzing two certified reference materials (BCR-142 and RS-3). The relative
      standard deviation for all target elements was below 8% indicating an adequate
      precision and the limit of detection ranged from 0.03 MUg g(-1) (Cd) to 24.0 MUg
      g(-1) (Fe). The concentrations of Al, As, Ba, Cd, Cu, Fe, Mg, Mn, Ni, Pb, Sr, and
      Zn in the different layers (0-10, 10-20, 20-40, and 40-60 cm) were determined in
      two types of soils, located in Parana State in Brazil. The soil layers analysis
      revealed a different behavior of metals concentrations in soil samples under NT
      and NV. The obtained results showed a clear impact of anthropogenic action with
      respect to specific metals due to many years of uncontrolled application rates of
      limestone and phosphate fertilizers.

PMID- 26220782
TI  - Neutron activation analysis of thermal power plant ash and surrounding area
      soils.
AB  - Elemental concentrations of As, Cd, Co, Cr, Fe, Hg, Mo, Ni, Se, and Zn have been
      determined in fly and bottom ash collected from Syrian power plants fired by
      heavy oil and natural gas using instrumental neutron activation analysis. The
      results showed that all elements were more concentrated in fly ash than in the
      fly ash; there was a clear increasing trend of the elemental concentrations in
      the fly ash along the flue gas pathway. The annual emission of elements was
      estimated. Elemental concentrations were higher inside the campus area than in
      surrounding areas, and the lowest values were found in natural-gas-fired power
      plant. In addition, the levels have decreased as the distance from power plant
      campus increases. However, the levels in the surrounding villages were within the
      Syrian standard for agriculture soil. 

PMID- 26220783
TI  - DYVIPAC: an integrated analysis and visualisation framework to probe multi
      dimensional biological networks.
AB  - Biochemical networks are dynamic and multi-dimensional systems, consisting of
      tens or hundreds of molecular components. Diseases such as cancer commonly arise
      due to changes in the dynamics of signalling and gene regulatory networks caused
      by genetic alternations. Elucidating the network dynamics in health and disease
      is crucial to better understand the disease mechanisms and derive effective
      therapeutic strategies. However, current approaches to analyse and visualise
      systems dynamics can often provide only low-dimensional projections of the
      network dynamics, which often does not present the multi-dimensional picture of
      the system behaviour. More efficient and reliable methods for multi-dimensional
      systems analysis and visualisation are thus required. To address this issue, we
      here present an integrated analysis and visualisation framework for high
      dimensional network behaviour which exploits the advantages provided by parallel
      coordinates graphs. We demonstrate the applicability of the framework, named
      "Dynamics Visualisation based on Parallel Coordinates" (DYVIPAC), to a variety of
      signalling networks ranging in topological wirings and dynamic properties. The
      framework was proved useful in acquiring an integrated understanding of systems
      behaviour. 

PMID- 26220784
TI  - Internet Versus DVD Decision Aids for Hip and Knee Osteoarthritis.
AB  - INTRODUCTION: Decision aids (DAs) can improve multiple decision-making outcomes,
      but it is not known whether different formats of delivery differ in their
      effectiveness or acceptability. The present study compared the effectiveness and
      acceptability of internet and DVD formats of DAs for osteoarthritis (OA).
      METHODS: Patients with hip or knee OA were randomized to view an internet or DVD
      format DA, which provided information on OA treatments. Measures were collected
      at baseline, immediately after viewing the DA and then 30 days later. Outcomes
      included: Hip/Knee OA Decision Quality Instrument - Knowledge Subscale (HK-DQI
      Knowledge), Decisional Conflict Scale (DCS), Preparation for Decision Making
      Scale (PDMS), Stage of Decision Making, and Acceptability of DAs. Generalized
      estimating equations (GEE) were used to examine changes in HK-DQI Knowledge and
      DCS scores over time, between decision aid groups and within the sample overall.
      Group differences in the PDMS scale (assessed once, immediately after DA viewing)
      were estimated using a Wilcoxon rank sums test. RESULTS: Among 155 participants
      in the study, the mean age was 61.8 years, 60.6% were women and 58.1% were
      Caucasian. HK-DQI Knowledge scores improved over time (p < 0.001), although there
      was some attenuation by the 30-day follow-up; there was no difference between the
      two DA groups (p = 0.448). DCS scores decreased markedly for both groups (p <
      0.001) and improvements were maintained by the 30-day follow-up (means: internet:
      baseline = 25.0, 30-day = 6.9; DVD: baseline = 25.0, 30-day = 6.2); there was no
      difference between the two DA groups (p = 0.808). PDMS scores were higher for the
      DVD group than the internet group (85.2 versus 74.9, p = 0.005). Stage of
      Decision Making became more certain after viewing the DA for both groups, with
      even more certainty indicated at 30-day follow-up. Acceptability items indicated
      positive perceptions of both DAs. DISCUSSION: Internet and DVD DAs were
      associated with meaningful, comparable improvements in decision-making outcomes
      in patients with knee and hip OA. DAs are inexpensive to disseminate and could be
      valuable tools for enhancing care for OA. Copyright (c) 2015 John Wiley & Sons,
      Ltd.

PMID- 26220785
TI  - Placental morphology in two sympatric Andean lizards of the genus Liolaemus
      (Reptilia: Liolaemidae).
AB  - Viviparity is a remarkable feature in squamate sauropsids and it has evolved
      multiple times in parallel with the formation of a placenta. One example of this
      repeated evolution of viviparity and placentation occurs in the species-rich
      South American genus Liolaemus with at least six independent origins of
      viviparity. However, evolutionary studies of placentation in this genus are
      limited by a lack of data on placental morphology. The aim of this study is to
      describe and compare the microanatomy and vessel diameter (Dv, a function of
      blood flow) of the placenta using scanning electron microscopy (SEM) and confocal
      laser scanning microscopy (cLSM) in two sympatric Andean viviparous but highly
      divergent species, Liolaemus robustus and Liolaemus walkeri. We found
      interspecific differences in cell types in the chorion, allantois, and
      omphalopleure that may be explained by divergent phylogenetic history. Time
      elapsed since divergence may also explain the pronounced interspecific
      differences in vessel diameter, and within each species, there are strong
      differences in Dv between tissue locations. Both species show features to improve
      gas exchange in the chorioallantoic placenta including absence of eggshell, large
      Dv in the allantois (L. robustus) or embryonic side of the uterus (L. walkeri),
      and when present, microvillous cells in the allantois (L. walkeri). Both species
      also show features that suggest transfer of nutrients or water in the
      omphaloplacenta, including an almost complete reduction of the eggshell,
      secretive material (L. robustus), or vesicles (L. walkeri) on cell surface
      uterus, and when present specialized cells in the omphalopleure (L. walkeri). No
      statistical differences in Dv were found among stages 32-39 in each species,
      suggesting that a different mechanism, other than enhanced blood flow, might
      satisfy the increased oxygen demand of the developing embryos in the hypoxic
      environments of the high Andes.

PMID- 26220786
TI  - Prevalence and Correlates of ADHD Among Adolescent Students in Nigeria.
AB  - OBJECTIVE: To determine the prevalence and psychosocial correlates of ADHD among
      adolescents in Jos, Nigeria. METHOD: A cross-sectional descriptive two-stage
      study of 487 randomly selected participants using Kiddie-Schedule for Affective
      Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL), Raven's
      Standard Progressive Matrix (SPM) and the Children's Global Assessment Score
      (CGAS). RESULTS: The prevalence of ADHD was 8.8%. The subtypes found were
      inattentive (3.08%), hyperactive-impulsive (2.05%), and combined (3.08%);
      male:female ratio of 1.4:1. ADHD was significantly associated with use of
      substance by father (odds ratio [OR] = 0.35; 95% confidence interval [CI] =
      [0.154, 0.781]), use of substance by mother (OR = 0.2; 95% CI = [0.055, 0.711]),
      and lower education of mother (OR = 0.3 95% CI = [0.116, 0.693]). Poor quality of
      handwriting (chi2 = 8.120; p = .010) and impaired global functioning ( t test =
      10.756; p < .001) were significantly associated with ADHD in the adolescents.
      CONCLUSION: Given the burden of ADHD, efforts should be made to establish a
      system for the early identification and management.

PMID- 26220787
TI  - The Effects of Different Types of Environmental Noise on Academic Performance and
      Perceived Task Difficulty in Adolescents With ADHD.
AB  - OBJECTIVE: To examine the effects of environmental noises (speech and white
      noise) relative to a no noise control condition on the performance and difficulty
      ratings of youth with ADHD (N = 52) on academic tasks. METHOD: Reading
      performance was measured by an oral retell (reading accuracy) and the time spent
      reading. Writing performance was measured through the proportion of correct
      writing sequences (writing accuracy) and the total words written on an essay.
      RESULTS: Participants in the white noise condition took less time to read the
      passage and wrote more words on the essay compared with participants in the other
      conditions, though white noise did not improve academic accuracy. The
      participants in the babble condition rated the tasks as most difficult.
      CONCLUSION: Although white noise appears to improve reading time and writing
      fluency, the findings suggest that white noise does not improve performance
      accuracy. Educational implications are discussed.

PMID- 26220788
TI  - A Familial Risk Analysis of Emotional Dysregulation: A Controlled Study.
AB  - OBJECTIVE: Children with deficits in emotional regulation operationalized by
      scores on the Child Behavior Checklist (CBCL) Attention Problems, Aggressive
      Behavior, and Anxious-Depressed subscales are more likely than others to manifest
      adverse outcomes. However, the transmission of this profile has not been well
      studied. The main aim of this study was to investigate the familiality of this
      profile. METHOD: Participants were youth probands with bipolar I (BP-I) disorder
      ( N = 140), ADHD ( N = 83), and controls ( N = 117) and their siblings. Based on
      the CBCL emotional dysregulation profile, we classified children with severe
      emotional dysregulation (aggregate cut-off score >=210) and emotional
      dysregulation (aggregate cut-off score >= 180 and <210). RESULTS: Emotional
      dysregulation profile scores correlated positively between probands and siblings.
      CONCLUSION: Youth with emotional dysregulation are at increased risk to have
      siblings with similar deficits, suggesting that emotional dysregulation runs in
      families.

PMID- 26220789
TI  - Hepatopulmonary Fistula: a life threatening complication of hydatid disease.
AB  - Despite extensive infection control measures against parasitic diseases, hydatid
      disease, caused by Echinococcus granulosus, still occurs in a minor group of our
      population. If the infection is not treated adequately, it goes on to developing
      life-threatening complications, one of which is hepatopulmonary fistula. These
      complications usually warrant early surgical intervention, or else may lead to
      extensive sepsis and ultimately death. We discuss the case of an elderly female
      suffering from pulmonary hydatid disease, further complicated by a
      hepatopulmonary fistula and underwent surgical treatment. This case emphasises
      the importance of early recognition of pulmonary hydatid disease given its
      atypical nature of presentation before the disease is further exacerbated by this
      aggressive complication. Furthermore, it is imperative to incorporate radical
      surgery as the first-line treatment in established hepatopulmonary fistula, in
      order to prevent further clinical deterioration and curative outcome. 

PMID- 26220790
TI  - Herpes zoster sciatica mimicking lumbar canal stenosis: a case report.
AB  - BACKGROUND: Symptom of herpes zoster is sometimes difficult to distinguish from
      sciatica induced by spinal diseases, including lumbar disc herniation and spinal
      canal stenosis. Here we report a case of sciatica mimicking lumbar canal
      stenosis. CASE PRESENTATION: A 74-year-old Chinese male patient visited our
      hospital for left-sided sciatic pain upon standing or walking for 5 min of
      approximately 1 month's duration. At the first visit to our hospital, there were
      no skin lesions. A magnetic resonance imaging showed spinal canal stenosis
      between the 4th and 5th lumbar spine. Thus, we diagnosed the patient with
      sciatica induced by spinal canal stenosis. We considered decompression surgery
      for the stenosis of 4th and 5th lumbar spine because conservative therapy failed
      to relieve the patient's symptom. At that time, the patient complained of a skin
      rash involving his left foot for several days. A vesicular rash and erythema were
      observed on the dorsal and plantar surfaces of the great toe and lateral
      malleolus. The patient was diagnosed with herpes zoster in the left 5th lumbar
      spinal nerve area based on clinical findings, including the characteristics of
      the pain and vesicular rash and erythema in the 5th lumbar spinal dermatome. The
      patient was treated with famciclovir (1,500 mg/day) and non-steroidal anti
      inflammatory drugs. After 1 week of medication, the skin rash resolved and pain
      relief was obtained. CONCLUSION: In conclusion, spinal surgeons should keep in
      mind herpes zoster infection as one of the possible differential diagnoses of
      sciatica, even if there is no typical skin rash.

PMID- 26220791
TI  - A means to an interface: investigating monoethanolamine behavior at an aqueous
      surface.
AB  - The use of amine scrubbers to trap carbon dioxide from flue gas streams is one of
      the most promising avenues for atmospheric carbon dioxide reduction. However,
      modifications are necessary to efficiently scale these scrubbers for use in
      fossil fuel plants. Current advances in tailoring amines for CO2 capture involve
      improvements of bulk kinetic and thermodynamic parameters, with little
      consideration to surface chemistry and behavior. Aqueous alkanolamine solutions,
      such as monoethanolamine (MEA), are currently highly favored sorbents in CO2 post
      combustion capture. Although numerous studies have explored MEA-CO2 chemistry at
      the macroscopic scale, few have investigated the role of the interface in the gas
      adsorption process. Additionally, as these amines become more industrially
      ubiquitous, their presence on and the need to understand their behavior at
      atmospheric and environmental surfaces will increase. This study investigates the
      surface behavior of monoethanolamine at the vapor/water interface, with
      particular focus on MEA's surface orientation and footprint. Using vibrational
      sum frequency spectroscopy, surface tensiometry, and computational techniques,
      MEA is found to adopt a constrained gauche interfacial conformation with its
      methylene backbone oriented toward the vapor phase and its functional groups
      solvated in the bulk solution. Computational and experimental analysis agree
      well, giving a complete picture with vibrational mode assignments and surface
      orientation of MEA. These findings can assist in the tailoring of amine
      structures or to facilitate improvements in engineering design to exploit
      favorable surface chemistry, as well as to serve as a starting point toward
      understanding aqueous amine surface behavior relevant to environmental systems. 

PMID- 26220792
TI  - Analysis artefacts of the INS-IGF2 fusion transcript.
AB  - BACKGROUND: In gene expression analysis, overlapping genes, splice variants, and
      fusion transcripts are potential sources of data analysis artefacts, depending on
      how the observed intensity is assigned to one, or more genes. We here exemplify
      this by an in-depth analysis of the INS-IGF2 fusion transcript, which has
      recently been reported to be among the highest expressed transcripts in human
      pancreatic beta cells and its protein indicated as a novel autoantigen in Type 1
      Diabetes. RESULTS: Through RNA sequencing and variant specific qPCR analyses we
      demonstrate that the true abundance of INS-IGF2 is >20,000 fold lower than INS in
      human beta cells, and we suggest an explanation to the nature of the artefacts
      which have previously led to overestimation of the gene expression level in
      selected studies. We reinvestigated the previous reported findings of detection
      of INS-IGF2 using antibodies both in Western blotting and immunohistochemistry.
      We found that the one available commercial antibody (BO1P) raised against
      recombinant INS-IGF2 show strong cross-reaction to native proinsulin, and we did
      not detect INS-IGF2 protein in the human beta cell line EndoC-betaH1.
      Furthermore, using highly sensitive proteomics analysis we could not demonstrate
      INS-IGF2 protein in samples of human islets nor in EndoC-betaH1. CONCLUSIONS:
      Sequence features, such as fusion transcripts spanning multiple genes can lead to
      unexpected results in gene expression analysis, and care must be taken in
      generating and interpreting the results. For the specific case of INS-IGF2 we
      conclude that the abundance of the fusion transcript/protein is exceedingly lower
      than previously reported, and that current immuno-reagents available for
      detecting INS-IGF2 protein have a strong cross-reaction to native human
      proinsulin. Finally, we were unable to detect INS-IGF2 protein by proteomics
      analysis.

PMID- 26220793
TI  - Microbacterium nanhaiense sp. nov., an actinobacterium isolated from sea
      sediment.
AB  - A Gram-staining-positive, heterotrophic, anaerobic, non-spore-forming, non
      motile, rod-shaped strain, OAct400T, belonging to the genus Microbacterium was
      isolated from a sediment collected from a depth of 2093 m in the South China Sea,
      China. The strain was identified using a polyphasic taxonomic approach. The
      strain grew well on yeast extract/malt extract agar (ISP 2) and nutrient agar
      media, and formed no aerial mycelium and no diffusible pigments on any media
      tested. The strain grew in the presence of 0-8 % (w/v) NaCl (optimum, 2-4 %), at
      pH 5.0-10.0 (optimum, pH 7.0) and at 4-37  degrees C (optimum, 28  degrees C).
      Strain OAct400T contained ornithine as the diagnostic diamino acid. The whole
      cell sugars were dominated by glucose and galactose. The predominant menaquinones
      were MK-11 (51 %) and MK-10 (24 %). The major phospholipids were
      phosphatidylglycerol and diphosphatidylglycerol. The major fatty acids were
      anteiso-C15 : 0 (59.35 %), iso-C16 : 0 (17.89 %) and anteiso-C17 : 0 (16.09 %).
      DNA-DNA relatedness with Microbacterium amylolyticum DSM 24221T and
      Microbacterium gubbeenense CIP 107184T, the nearest phylogenetic relatives (97.73
      and 97.44 % 16S rRNA gene sequence similarity, respectively) was 31.3 +/- 2.1 and
      28.7 +/- 1.2 %, respectively. On the basis of phenotypic, phylogenetic and
      genotypic data, a novel species, Microbacterium nanhaiense sp. nov., is proposed.
      The type strain is OAct400T ( = CGMCC 4.7181T = DSM 26811T = KCTC 29185T). 

PMID- 26220794
TI  - Renal related disorders in concomitant Schistosoma haematobium-Plasmodium
      falciparum infection among children in a rural community of Nigeria.
AB  - Schistosomiasis and malaria are two common parasitic diseases that are co-endemic
      in resource-poor communities of sub-Saharan Africa. This study aims to assess the
      effects of single and concomitant Plasmodium falciparum and Schistosoma
      haematobium infections on two indicators of renal injury in school children in a
      rural community of Nigeria. A cross-sectional epidemiological survey was carried
      out on a total of 173 schoolchildren between ages 6 and 18 years (mean age 11.4+/
      2.6 years). Urine and blood samples were collected by standard methods for
      concurrent microscopic diagnosis of S. haematobium and P. falciparum infections.
      Urinary blood (hematuria) and protein were determined using a urinalysis
      dipstick. The prevalence of single infections was 75.1% and 78.2% for S.
      haematobium and P. falciparum, respectively. A total of 57.1% individuals were
      infected with the two parasites. The prevalence of hematuria was significantly
      higher in the co-infection status (63.8%) than in single S. haematobium (52.2%)
      and P. falciparum (43.7%) infection statuses (p=0.04), while no significant
      variation was recorded in proteinuria in the three infection statuses (p=0.53).
      The proportion of children with renal injury associated with the co-infection of
      these parasites is very high, particularly in young children, who seem to have a
      higher prevalence of hematuria.

PMID- 26220795
TI  - Detection of Clostridium tetani in human clinical samples using tetX specific
      primers targeting the neurotoxin.
AB  - Tetanus resulting from ear injury remains an important health problem,
      particularly in the developing world. We report the successful detection of
      Clostridium tetani using tetX specific primers targeting the Cl. tetani
      neurotoxin. The sample was obtained from an ear discharge of a case of otogenic
      tetanus in a 2-year-old male child. Based on the culture results of the ear
      discharge, Gram staining and virulence testing by genotyping, a diagnosis of
      tetanus was confirmed. This is the first report from India on the successful
      detection of Cl. tetani in a human clinical sample using tetX specific primers
      targeting the Cl. tetani neurotoxin. 

PMID- 26220796
TI  - Pituitary adenoma apoplexy caused by rupture of an anterior communicating artery
      aneurysm: case report and literature review.
AB  - BACKGROUND: Pituitary adenoma combined with intracranial aneurysm is not rare.
      Some aneurysms are located inside pituitary adenomas, and most do not rupture.
      Pituitary apoplexy caused by aneurysm rupture is rare and is easily misdiagnosed
      as simple pituitary adenoma apoplexy. CASE PRESENTATION: In this study, we report
      one case of rare pituitary adenoma apoplexy caused by the rupture of an anterior
      communicating artery aneurysm. The patient was a 49-year-old male who had an
      untreated pituitary adenoma for 3 years. The patient experienced a sudden
      headache; computed tomography (CT) and magnetic resonance imaging (MRI) revealed
      pituitary adenoma apoplexy and significant subarachnoid hemorrhage. Cranial CT
      angiography (CTA) showed a communicating artery aneurysm. Supratentorial
      intracranial aneurysm clipping and pituitary adenoma resection were performed.
      The aneurysm was a ruptured aneurysm located inside the pituitary adenoma. During
      the surgery, the aneurysm was clipped, and the majority of the tumor was
      resected. The patient recovered well after the surgery and received radiotherapy.
      CONCLUSIONS: This rare case demonstrates that when pituitary adenoma apoplexy is
      combined with subarachnoid hemorrhage, the possibility of a combined intrasellar
      aneurysm should be considered. During transsphenoidal tumor resection, aneurysm
      rupture should be avoided to prevent disastrous consequences.

PMID- 26220797
TI  - The DNA index as a prognostic tool in hilar cholangiocarcinoma.
AB  - BACKGROUND AND OBJECTIVES: Due to the devastating prognosis of patients suffering
      from hilar cholangiocarcinoma (HCCA) valid prognostic factors are urgently needed
      to guide treatment decisions in a personalized concept. The aim of this study was
      to analyze the predictive value of the DNA index in a large single-center cohort
      of patients undergoing resection of HCCA. METHODS: A total of 154 patients who
      underwent resection of HCCA were included in this prospective study. The DNA
      index was assessed by image cytometry of fresh tumor samples and correlated, as
      well as standard histopathological parameters, with patient survival. RESULTS:
      The median DNA index was 1.61 +/- 0.32. Univariate survival analysis identified
      eight parameters including DNA index, but not DNA ploidy as prognostic markers.
      In the Cox proportional hazard model DNA index (P = 0.021), tumor size (P =
      0.029) and lymph nodes status (P = 0.039) could be shown to be independent
      predictors of patient survival. CONCLUSION: The DNA index represents an
      independent prognostic marker in HCCA which is superior to most standard
      histopathological factors. Since the DNA index can be assessed not only post- but
      also preoperatively, it might be a potential tool in the preoperative decision
      making process.

PMID- 26220798
TI  - Repeated intranasal exposure to microcystin-LR affects lungs but not nasal
      epithelium in mice.
AB  - Microcystin-LR (MC-LR) is a harmful cyanotoxin able to induce adverse outcomes in
      the respiratory system. We aimed to examine the lungs and nasal epithelium of
      mice following a sub-chronic exposure to MC-LR. Swiss mice were intranasally
      instilled with 10 MUL of distilled water (CTRL, n = 10) or 6.7 ng/kg of MC-LR
      diluted in 10 MUL of distilled water (TOX, n = 8) during 30 consecutive days.
      Respiratory mechanics was measured in vivo and histology measurements (morphology
      and inflammation) were assessed in lungs and nasal epithelium samples 24 h after
      the last intranasal instillation. Despite the lack of changes in the nasal
      epithelium, TOX mice displayed an increased amount of PMN cells in the lungs (*
      10(-3)/MUm(2)), higher lung static elastance (cmH2O/mL), resistive and
      viscoelastic/inhomogeneous pressures (cmH2O) (7.87 +/- 3.78, 33.96 +/- 2.64, 1.03
      +/- 0.12, 1.01 +/- 0.08, respectively) than CTRL (5.37 +/- 4.02, 26.65 +/- 1.24,
      0.78 +/- 0.06, 0.72 +/- 0.05, respectively). Overall, our findings suggest that
      the nasal epithelium appears more resistant than lungs in this model of MC-LR
      intoxication.

PMID- 26220799
TI  - beta/delta-PrIT1, a highly insecticidal toxin from the venom of the Brazilian
      spider Phoneutria reidyi (F.O. Pickard-Cambridge, 1897).
AB  - A potent insecticidal toxin, beta/delta-PrIT1, molecular mass of 5598.86
      [M+H](+), was characterized from Phoneutria reidyi spider venom. Its partial
      amino acid sequence showed high similarity with insecticidal spider toxins from
      the genus Phoneutria. beta/delta-PrIT1 was very toxic (LD50 = 4 nmol/g) to flies
      (Musca domestica), but not to mice (Mus musculus). Kinetic studies showed that
      (125)I-beta/delta-PrIT1 binds to two distinct sites in insect sodium channels,
      with close affinity (Kd1 = 34.7 pM and Kd2 = 35.1 pM). Its association is rather
      fast (t1/2(1) = 1.4 min, t1/2(2) = 8.5 min) and its dissociation is a slower
      process (t1/2(1) = 5.4 min, t1/2(2) = 32.8 min). On rat brain synaptosomes
      beta/delta-PrIT1 partially competed (~30%) with the beta-toxin (125)I-CssIV, but
      did not compete with the alpha-toxin of reference (125)I-AaII, nor with the beta
      toxin (125)I-TsVII. On cockroach nerve cord synaptosomes, beta/delta-PrIT1 did
      not compete with the anti-insect toxin (125)I-LqqIT1, but it competed (IC50 = 80
      pM) with the "alpha-like" toxin (125)I-BomIV. In cockroach neurons, beta/delta
      PrIT1 inhibited the inactivation of Nav-channels and it shifted the sodium
      channel activation to hyperpolarizing potentials. These results indicate two
      different binding sites for beta/delta-PrIT1, leading to two different
      pharmacological responses. beta/delta-PrIT1 is one of the most toxic spider
      toxins to insects without apparent toxicity to mammals, and provide new model for
      the development of insecticides.

PMID- 26220800
TI  - Using the MMPB technique to confirm microcystin concentrations in water measured
      by ELISA and HPLC (UV, MS, MS/MS).
AB  - Microcystins have been detected in raw and finished drinking water using a
      variety of techniques, including assays (immunoassay, phosphatase inhibition) and
      HPLC (UV, MS/(MS)). The principal challenge to microcystin analysis is accounting
      for the over 150 variants that have been described. A confirmatory individual
      variant HPLC analysis is prone to under-reporting total microcystins due to
      method specificity. One method that allows for total microcystin quantitation is
      the MMPB technique. In this study, water samples with native microcystins were
      oxidized to cleave the Adda moiety, common to all microcystin variants. LC-MS/MS
      analysis was conducted on the subsequent MMPB (3-methoxy-2-methyl-4-phenylbutyric
      acid) molecule and calibrated using a certified reference standard (microcystin
      LR) and 4-phenylbutyric acid. Total microcystin concentrations from MMPB were
      compared to Adda ELISA and individual variant analyses (LC-UV, LC-MS/(MS)).
      Variants of microcystin, including [DAsp(3)]MC-RR, [Dha(7)]MC-RR, MC-RR, MC-YR,
      MC-LR, [DAsp(3)]MC-LR, [Dha(7)]MC-LR, MC-WR, MC-LA, and MC-LY were detected and
      quantified in samples. The individual variant analyses did not account for total
      microcystins present in samples, as indicated by ELISA and MMPB data. Results
      demonstrated the MMPB technique is a simple and valuable approach to confirm
      ELISA data when analyzing microcystins, with method detection limits of 0.05 MUg
      L(-1) for total microcystins.

PMID- 26220801
TI  - Explanation of timing of botulinum neurotoxin effects, onset and duration, and
      clinical ways of influencing them.
AB  - While the steps in the action of botulinum neurotoxin (BoNT) are well known, the
      factors underlying the timing of these steps are not fully understood. After
      toxin is injected into a muscle, it resides in the extracellular space and must
      be taken up into the nerve terminals. More toxin will be taken up if near the
      endplate. Toxin is distributed mainly by convection and there is likely little
      diffusion. Toxin that is not taken up will go into the general circulation where
      it may have a slight systemic effect. The uptake is activity and temperature
      dependent. Encouraging the unwanted muscle contractions after injection should be
      helpful. Cooling will decrease the uptake. The times for washout from the
      extracellular space and uptake of the toxin are not well established, but are
      likely measured in minutes. Toxin in the general circulation has a long half
      time. The time from injection to weakness is determined by how long it takes to
      get sufficient damage of the SNARE proteins to interfere with synaptic release.
      Toxins are zinc dependent proteases, and supplemental zinc may produce a greater
      effect. There will be weakness as long as there is residual toxin in the nerve
      ending.

PMID- 26220802
TI  - Daily electronic self-monitoring in bipolar disorder using smartphones - the
      MONARCA I trial: a randomized, placebo-controlled, single-blind, parallel group
      trial.
AB  - BACKGROUND: The number of studies on electronic self-monitoring in affective
      disorder and other psychiatric disorders is increasing and indicates high patient
      acceptance and adherence. Nevertheless, the effect of electronic self-monitoring
      in patients with bipolar disorder has never been investigated in a randomized
      controlled trial (RCT). The objective of this trial was to investigate in a RCT
      whether the use of daily electronic self-monitoring using smartphones reduces
      depressive and manic symptoms in patients with bipolar disorder. METHOD: A total
      of 78 patients with bipolar disorder according to ICD-10 criteria, aged 18-60
      years, and with 17-item Hamilton Depression Rating Scale (HAMD-17) and Young
      Mania Rating Scale (YMRS) scores <=17 were randomized to the use of a smartphone
      for daily self-monitoring including a clinical feedback loop (the intervention
      group) or to the use of a smartphone for normal communicative purposes (the
      control group) for 6 months. The primary outcomes were differences in depressive
      and manic symptoms measured using HAMD-17 and YMRS, respectively, between the
      intervention and control groups. RESULTS: Intention-to-treat analyses using
      linear mixed models showed no significant effects of daily self-monitoring using
      smartphones on depressive as well as manic symptoms. There was a tendency towards
      more sustained depressive symptoms in the intervention group (B = 2.02, 95%
      confidence interval -0.13 to 4.17, p = 0.066). Sub-group analysis among patients
      without mixed symptoms and patients with presence of depressive and manic
      symptoms showed significantly more depressive symptoms and fewer manic symptoms
      during the trial period in the intervention group. CONCLUSIONS: These results
      highlight that electronic self-monitoring, although intuitive and appealing,
      needs critical consideration and further clarification before it is implemented
      as a clinical tool.

PMID- 26220803
TI  - Efficacy and External Validity of Electronic and Mobile Phone-Based Interventions
      Promoting Vegetable Intake in Young Adults: A Systematic Review Protocol.
AB  - BACKGROUND: Despite social marketing campaigns and behavior change interventions,
      young adults remain among the lowest consumers of vegetables. The digital era
      offers potential new avenues for both social marketing and individually tailored
      programs, through texting, web, and mobile applications. The effectiveness and
      generalizability of such programs have not been well documented. OBJECTIVE: The
      aim of this systematic review is to evaluate the efficacy and external validity
      of social marketing, electronic, and mobile phone-based (mHealth) interventions
      aimed at increasing vegetable intake in young adults. METHODS: The Preferred
      Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol will
      be used to conduct this systematic review. The search strategy will be executed
      across eleven electronic databases using combinations of the following search
      terms: "online intervention", "computer-assisted therapy", "internet", "website",
      "cell phones", "cyber", "telemedicine", "email", "social marketing", "social
      media", "mass media", "young adult", and "fruit and vegetables". The reference
      lists of included studies will also be searched for additional citations. Titles
      and abstracts will be screened against inclusion criteria and full texts of
      potentially eligible papers will be assessed by two independent reviewers. Data
      from eligible papers will be extracted. Quality and risk of bias will be assessed
      using the Effective Public Health Practice Project (EPHPP) Quality Assessment
      Tool for Quantitative Studies and The Cochrane Collaboration Risk of Bias
      assessment tool respectively. The external validity of the studies will be
      determined based on components such as reach, adoption, and representativeness of
      participants; intervention implementation and adaption; and program maintenance
      and institutionalization. Results will be reported quantitatively and
      qualitatively. RESULTS: Our research is in progress. A draft of the systematic
      review is currently being produced for publication by the end of 2015.
      CONCLUSIONS: The review findings will assist the design and implementation of
      future eHealth and mHealth programs aimed at improving vegetable consumption in
      young adults. TRIAL REGISTRATION: PROSPERO International Prospective Register of
      Systematic Reviews: CRD42015017763;
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015017763#.VVKtqfmq
      ko (Archived by WebCite at http://www.webcitation.org/6YU2UYrTn).

PMID- 26220804
TI  - Factors associated with DELAY in diagnosis among tuberculosis patients in Hohoe
      Municipality, Ghana.
AB  - BACKGROUND: Any delay in diagnosis and consequently treatment of TB patients not
      only increases the infectivity of the disease in the community, but may also lead
      to more advance disease state, which may result in more complications and expose
      patients to higher risk of death. The aim of this study was to assess delays in
      diagnosing new TB patients and the factors associated with these delays in Hohoe
      Municipality of Ghana. METHODS: A cross sectional study was carried out among 73
      new TB Patients, 15 years or older, registered between 1st June, 2013 and 31st
      May, 2014 in Hohoe Municipality. Questionnaires were administered to patients to
      evaluate factors related to delay by patients in seeking care, delays at
      healthcare facilities, and total diagnostic delay. Logistic regression was used
      to determine the factors associated with patient delay (>30 days), healthcare
      services delay (>15 days), and total delay (>45 days). RESULTS: The median total
      delay was 104 days (inter-quartile range (IQR):17-191). The median patient delay
      was 59 days (IQR: 5-123), and the median healthcare services delay was 45 days
      (IQR: 38-128). Not medically insured (AOR = 6.12; 95 % CI: 1.26-29.88; P < 0.025)
      and perceived stigma (AOR = 5.30; 95 % CI: 1.33-21.18; P < 0.018) were risk
      factors associated with prolonged patient delay. Multiple healthcare contact
      following signs and symptoms (AOR = 10.26; 95 %CI: 2.95-35.72; P < 0.0001) was
      the only risk factor associated with prolonged healthcare services delay.
      CONCLUSION: There is a considerable delay in TB case detection mainly due to
      patients delay in seeking healthcare. The factors associated with patients' delay
      include lack of medical insurance, perceived stigma, and making multiple
      healthcare encounters. Health system strengthening towards decentralizing TB
      diagnosis and management, raising public awareness about the disease, training of
      healthcare providers, and collaborating with non-formal healthcare providers may
      reduce long delays in the management of TB.

PMID- 26220805
TI  - Facile Assembly of Chiral Metallosquares by Using Enantiopure
      Tribenzotriquinacene Corner Motifs.
AB  - Invited for the cover of this issue are Wen-Rong Wu, Guang-Jie Xia, and Hak-Fun
      Chow of The Chinese University of Hong Kong, Xiao-Ping Cao of Lanzhou University
      and Dietmar Kuck of Bielefeld University. The image depicts how different routes
      can lead to the same goal. Read the full text of the article at
      10.1002/chem.201501556. 

PMID- 26220806
TI  - Introduction of a catalytic triad increases the glutathione peroxidase-like
      activity of diaryl diselenides.
AB  - Reactive oxygen species (ROS)-mediated diseased states are of major concern in
      modern day life. Under oxidative stress conditions, the cellular antioxidants
      deplete, leading to several biological disorders. Small molecule mimics of
      different antioxidant enzymes are found to be useful in supplementing the
      biological systems to detoxify ROS. In this study, we have synthesized a series
      of amine or amide-based diselenides containing an additional amino group as
      glutathione peroxidase (GPx) mimetics. These diselenides act as a catalytic triad
      model of the native GPx featuring two basic amino groups near the selenium
      centre. A comparison of the catalytic activities reveals that the additional
      amino group increases the activity significantly in the presence of aromatic
      thiols. Deprotonation of thiol by an additional amine either stabilizes the
      selenolate intermediate or facilitates the nucleophilic attack of thiol in other
      intermediates. The (77)Se NMR experiments and DFT calculations show that the
      amino group does not have any significant effect on the catalytic intermediates.
      Although the amino moiety increases the nucleophilicity of the thiol, it does not
      prevent the thiol exchange reactions that take place in the selenenyl sulfide
      intermediates. 

PMID- 26220807
TI  - Nonfunctional alleles of long-day suppressor genes independently regulate
      flowering time.
AB  - Due to the remarkable adaptability to various environments, rice varieties with
      diverse flowering times have been domesticated or improved from Oryza rufipogon.
      Detailed knowledge of the genetic factors controlling flowering time will
      facilitate understanding the adaptation mechanism in cultivated rice and enable
      breeders to design appropriate genotypes for distinct preferences. In this study,
      four genes (Hd1, DTH8, Ghd7 and OsPRR37) in a rice long-day suppression pathway
      were collected and sequenced in 154, 74, 69 and 62 varieties of cultivated rice
      (Oryza sativa) respectively. Under long-day conditions, varieties with
      nonfunctional alleles flowered significantly earlier than those with functional
      alleles. However, the four genes have different genetic effects in the regulation
      of flowering time: Hd1 and OsPRR37 are major genes that generally regulate rice
      flowering time for all varieties, while DTH8 and Ghd7 only regulate regional rice
      varieties. Geographic analysis and network studies suggested that the
      nonfunctional alleles of these suppression loci with regional adaptability were
      derived recently and independently. Alleles with regional adaptability should be
      taken into consideration for genetic improvement. The rich genetic variations in
      these four genes, which adapt rice to different environments, provide the
      flexibility needed for breeding rice varieties with diverse flowering times. 

PMID- 26220808
TI  - Maternal and fetal outcome in women with hypertensive disorders of pregnancy: the
      impact of prenatal care.
AB  - BACKGROUND: Hypertensive disorders of pregnancy (HDP) are the most important
      cause of maternal and fetal death and pregnancy complications in Latin America
      and the Caribbean. OBJECTIVES: The objective of this study was to characterize
      the epidemiological profile of women with HDP admitted to a Brazilian tertiary
      reference hospital, and to evaluate maternal and fetal outcome in each HDP and
      the impact of prenatal care on the maternal and fetal outcome. METHODS: HDP in
      1501 women were classified according to usual definitions as chronic hypertension
      (n = 564), pre-eclampsia (n = 579), eclampsia (n = 74) and pre
      eclampsia/eclampsia superimposed on chronic hypertension (n = 284). Adverse
      maternal and fetal outcomes registered as maternal death and near miss and fetal
      outcomes documented as stillbirth, neonatal death and newborn respiratory
      complications were compiled. Prenatal care was classified as complete (? 6
      visits), incomplete (< 6 visits) or not done. RESULTS: Women with eclampsia were
      younger (15 years), 68% were on their first pregnancy, had higher blood pressure,
      higher mortality and greater number of near miss cases and their children had
      lower birth weight, higher intra-uterus and neonatal mortality, and more
      respiratory distress. Women with pre-eclampsia/eclampsia superimposed on chronic
      hypertension and their fetuses had intermediate outcome and those with chronic
      hypertension and pre-eclampsia the better outcome among those with HDP. Women who
      had incomplete prenatal care or prenatal not done had progressive higher
      mortality rates and greater frequency of near miss cases, and their children had
      higher mortality rates. CONCLUSION: In a tertiary reference hospital, eclampsia
      and chronic hypertension superimposed on pre-eclampsia are associated with a
      worst outcome for mothers and fetuses, whereas complete prenatal care is
      associated with a better maternal and fetal outcome in HDP.

PMID- 26220809
TI  - Evaluation of inner and outer retinal thickness in patients receiving
      intravitreal ranibizumab injections for diabetic macular edema.
AB  - PURPOSE: To measure inner and outer retinal thickness with optical coherence
      tomography (OCT) in patients in whom intravitreal ranibizumab was administered
      due to diabetic macular edema (DME) and to investigate its relation to the visual
      prognosis. METHODS: In this retrospective case series, there were 60 consecutive
      eyes with DME in which intravitreal ranibizumab injection was performed for 3
      times in 1-month intervals. All patients underwent full ophthalmic examination
      and spectral-domain OCT (SD-OCT). The total retinal thickness, the inner
      thickness, and the outer thickness in 4 parafoveal subfields were measured. The
      correlation between the retinal thickness and logMAR best-corrected visual acuity
      (BCVA) was investigated. RESULTS: No significant correlation was found between
      the total retinal thickness in the central and other subfields and either the
      baseline or final visit logMAR BCVA values (p>0.05). There was a significant
      positive correlation between the final visit logMAR BCVA values and pretreatment
      inner retinal thickness in the nasal and inferior subfields (r = 0.270, p =
      0.037, and r = 0.410, p = 0.001, respectively). There was significant negative
      correlation between the final visit logMAR BCVA values and pretreatment outer
      retinal thickness in nasal and temporal parafoveal subfields (r = -0.297, p =
      0.021, and r = -0.268, p = 0.038, respectively). CONCLUSIONS: It could be
      beneficial to use inner and outer retinal thickness instead of total retinal
      thickness in determination of short-term prognosis in patients who had
      intravitreal ranibizumab injection for DME.

PMID- 26220810
TI  - Cancer and circulatory disease risks in US radiologic technologists associated
      with performing procedures involving radionuclides.
AB  - OBJECTIVES: The number of nuclear medicine procedures has increased substantially
      over the past several decades, with uncertain health risks to the medical workers
      who perform them. We estimated risks of incidence and mortality from cancer and
      circulatory disease associated with performing procedures involving the use of
      radionuclides. METHODS: From a nationwide cohort of 90,955 US radiologic
      technologists who completed a mailed questionnaire during 1994-1998, 22,039
      reported ever performing diagnostic radionuclide procedures, brachytherapy,
      radioactive iodine therapy, or other radionuclide therapy. We calculated
      multivariable-adjusted HRs and 95% CIs for incidence (through 2003-2005) and
      mortality (through 2008) associated with performing these procedures. RESULTS:
      Ever (versus never) performing radionuclide procedures was not associated with
      risks for most end points examined. However, we observed increased risks for
      squamous cell carcinoma of the skin (HR=1.29, 95% CI 1.01 to 1.66) with ever
      performing diagnostic radionuclide procedures, for myocardial infarction
      incidence (HR=1.37, 95% CI 1.10 to 1.70), all-cause mortality (HR=1.10, 95% CI
      1.00 to 1.20) and all-cancer mortality (HR=1.20, 95% CI 1.01 to 1.43) with ever
      performing brachytherapy, and for mortality from all causes (HR=1.14, 95% CI 1.01
      to 1.30), breast cancer (HR=2.68, 95% CI 1.10 to 6.51), and myocardial infarction
      (HR=1.76, 95% CI 1.02 to 3.04) with ever performing other radionuclide therapy
      procedures (excluding brachytherapy and radioactive iodine); increasing risks
      were also observed with greater frequency of performing these procedures,
      particularly before 1980. CONCLUSIONS: The modest health risks among radiologic
      technologists performing procedures using radionuclides require further
      examination in studies with individual dose estimates, more detailed information
      regarding types of procedures performed and radionuclides used, and longer follow
      up.

PMID- 26220811
TI  - Organocatalytic glycosylation by using electron-deficient pyridinium salts.
AB  - A new organocatalytic glycosylation method based on electron-deficient pyridinium
      salts is reported. At ambient temperature and catalyst loadings as low as 1 mol
      %, 2-deoxyglycosides were formed from benzyl- and silyl-protected glycals and
      primary or secondary glycosyl acceptors, with excellent yields and anomeric
      selectivity. Mechanistic investigations point to alcohol-pyridinium conjugates
      (1,2-addition products) as key intermediates in the catalytic cycle. 

PMID- 26220813
TI  - Tailoring counselling after pulmonary valve surgery in repaired tetralogy of
      Fallot.

PMID- 26220812
TI  - Type 2 myocardial infarction: the chimaera of cardiology?
AB  - The term type 2 myocardial infarction first appeared as part of the universal
      definition of myocardial infarction. It was introduced to cover a group of
      patients who had elevation of cardiac troponin but did not meet the traditional
      criteria for acute myocardial infarction although they were considered to have an
      underlying ischaemic aetiology for the myocardial damage observed. Since first
      inception, the term type 2 myocardial infarction has always been vague. Although
      attempts have been made to produce a systematic definition of what constitutes a
      type 2 myocardial infarction, it has been more often characterised by what it is
      not rather than what it is. Clinical studies that have used type 2 myocardial
      infarction as a diagnostic criterion have produced disparate incidence figures.
      The range of associated clinical conditions differs from study to study.
      Additionally, there are no agreed or evidence-based treatment strategies for type
      2 myocardial infarction. The authors believe that the term type 2 myocardial
      infarction is confusing and not evidence-based. They consider that there is good
      reason to stop using this term and consider instead the concept of secondary
      myocardial injury that relates to the underlying pathophysiology of the primary
      clinical condition. 

PMID- 26220814
TI  - Disaster Preparedness and Awareness of Patients on Hemodialysis after Hurricane
      Sandy.
AB  - BACKGROUND AND OBJECTIVES: Patients with ESRD on dialysis live in a complex
      sociomedical situation and are dependent on technology and infrastructure, such
      as transportation, electricity, and water, to sustain their lives. Interruptions
      of this infrastructure by natural disasters can result in devastating outcomes.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between November of 2013 and April
      of 2014, a cross-sectional survey was conducted of patients who received
      maintenance hemodialysis before and after the landfall of Hurricane Sandy on
      October 29, 2012 in lower Manhattan, New York. The primary outcome was the number
      of missed dialysis sessions after the storm. Dialysis-specific and general
      disaster preparedness were assessed using checklists prepared by the National
      Kidney Foundation and US Homeland Security, respectively. RESULTS: In total, 598
      patients were approached, and 357 (59.7%) patients completed the survey.
      Participants were 60.2% men and 30.0% black, with a median age of 60 years old;
      94 (26.3%) participants missed dialysis (median of two sessions [quartile 1 to
      quartile 3 =1-3]), and 236 (66.1%) participants received dialysis at nonregular
      dialysis unit(s): 209 (58.5%) at affiliated dialysis unit(s) and 27 (7.6%) at
      emergency rooms. The percentages of participants who carried their insurance
      information and detailed medication list were 75.9% and 44.3%, respectively.
      Enhancement of the dialysis emergency packet after the hurricane was associated
      with a significantly higher cache of medical records at home at follow-up survey
      (P<0.001, Fisher's exact test). Multivariate Poisson regression analysis showed
      that dialysis-specific preparedness (incidence rate ratio, 0.91; 95% confidence
      interval, 0.87 to 0.98), other racial ethnicity (incidence rate ratio, 0.34; 95%
      confidence interval, 0.20 to 0.57), dialysis treatment in affiliated units
      (incidence rate ratio, 0.69; 95% confidence interval, 0.51 to 0.94), and older
      age (incidence rate ratio, 0.98; 95% confidence interval, 0.97 to 0.99) were
      associated with a significantly lower incidence rate ratio of missed dialysis.
      CONCLUSIONS: There is still room to improve the preparedness for natural
      disasters of patients with ESRD. Provider- or facility-oriented enhancement of
      awareness of the disease and preparedness should be a priority.

PMID- 26220815
TI  - Preparing for Disasters for Patients on Dialysis.

PMID- 26220816
TI  - Remote Usability Testing and Satisfaction with a Mobile Health Medication Inquiry
      System in CKD.
AB  - BACKGROUND AND OBJECTIVES: Inappropriate medication use is common in the care of
      patients with CKD. The feasibility of a simple mobile health tool designed to
      advise patients on safe medication usage in CKD was examined. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Participants with predialysis CKD (defined as
      eGFR<60 ml/min per 1.73 m(2)) in the Safe Kidney Care Cohort Study were recruited
      for home usability testing of a novel medication inquiry system between January
      and September of 2013. Testing was through two mobile platforms: (1) short
      messaging service text or (2) personal digital assistant (e.g., iPod Touch).
      Twenty participants (one half assigned to one device and one half assigned to the
      other device) were enrolled and received an in-center tutorial on device usage
      before the end of the study visit. Participants were subsequently mailed three
      sample pill bottles with the name of randomly selected medications and asked to
      input these medications into the medication inquiry system. The medication
      inquiry system response options were as follows: (1) safe in CKD, (2) not safe in
      CKD, (3) use with caution/speak with your health care provider, or (4) error
      message (for an incorrectly inputted medication). Participants were asked to
      record the response issued by the medication inquiry system for each medication
      sent for usability testing. A user satisfaction survey was administered after
      completion of the protocol. RESULTS: All participants owned a mobile telephone,
      but few owned a smartphone. Of 60 total medication queries, there were only three
      recorded errors, two of which occurred in the short messaging service texting
      group. Overall satisfaction with the application was high, with slightly higher
      satisfaction noted in the personal digital assistant group compared with the
      short messaging service group. CONCLUSIONS: The mobile health medication inquiry
      system application had general ease of use and high acceptance across two
      platforms among individuals representative of the CKD population. Tailored mobile
      health technology may improve medication safety in CKD.

PMID- 26220817
TI  - Medication Safety + Mobile Health = Patient Engagement in CKD.

PMID- 26220818
TI  - Outpatient Dialysis for Patients with AKI: A Policy Approach to Improving Care.
AB  - The rate of AKI requiring dialysis has increased significantly over the past
      decade in the United States. At the same time, survival from AKI seems to be
      improving, and thus, more patients with AKI are surviving to discharge while
      still requiring dialysis. Currently, the options for providing outpatient
      dialysis in patients with AKI are limited, particularly after a 2012 revised
      interpretation of the Centers for Medicare and Medicaid Services guidelines,
      which prohibited Medicare reimbursement for acute dialysis at ESRD facilities.
      This article provides a historical perspective on outpatient dialysis management
      of patients with AKI, reviews the current clinical landscape of care for these
      patients, and highlights key areas of knowledge deficit. Lastly, policy changes
      that have the opportunity to significantly improve the care of this at-risk
      population are suggested. 

PMID- 26220819
TI  - Planned foveal detachment technique for the resolution of diffuse diabetic
      macular edema.
AB  - PURPOSE: To evaluate the therapeutic efficacy of a novel surgical procedure for
      diffuse diabetic macular edema (DME), performed in conjunction with conventional
      vitrectomy. METHODS: This prospective, interventional case series involved 20
      eyes of 18 consecutive DME patients with best-corrected visual acuities (BCVAs)
      between 0.301 and 1.221 logarithm of the minimal angle of resolution (logMAR)
      units and central retinal thicknesses (CRTs) greater than 275 MUm. After
      vitrectomy, a small retinal detachment was made in the macula by injecting 50-100
      MUl balanced salt solution into the subretinal space using a 38-gauge needle.
      Before finishing the surgery, fluid-air exchange was performed. Patients were
      asked to remain in prone position for 1 day postoperatively. The main outcome
      measures were CRT and BCVA. RESULTS: The mean CRT of 554.6 +/- 152.7 MUm before
      surgery significantly decreased to 295.6 +/- 92.5 MUm (p < 0.0001) 1 week after
      surgery and to 185.8 +/- 67.4 MUm (p < 0.0001) at 6 months after surgery. The CRT
      was less than 250 MUm in 18 eyes (90 %) at 6 months after surgery. The mean BCVA
      before surgery (0.706 +/- 0.348) significantly improved at 6 months after surgery
      (0.431 +/- 0.392, p < 0.0001). Postoperative BCVAs improved by more than 0.3
      logMAR units in 13 eyes (65 %), remained unchanged in six eyes (30 %) and
      worsened in one eye (5 %). Macular edema recurred in three eyes (15 %) 2 months
      after surgery. CONCLUSIONS: This novel planned foveal detachment technique
      facilitated a rapid resolution of DME and contributed to improved visual acuity.

PMID- 26220820
TI  - Changes in filtering bleb morphology after bleb-related infection.
AB  - PURPOSE: To verify, by use of data collected by the Japan Glaucoma Society Survey
      of Bleb-related Infection (JGSSBI), that bleb morphology changes within 12 months
      of the development of bleb-related infection. METHODS: JGSSBI data from 57 eyes
      of 57 patients with primary open-angle glaucoma and normal tension glaucoma who
      developed a bleb-related infection were analyzed. Morphological features of the
      blebs were graded by use of a predetermined grading system. Multiple logistic
      regression analysis was conducted to identify factors relating to bleb morphology
      which were associated with poor outcome. RESULTS: Bleb sizes, including both
      circumferential and tangential lengths, were significantly smaller for stage
      IIIa/IIIb infections than for stage I/II bleb infections (P = 0.009 and P = 0.026
      for the circumferential and tangential lengths, respectively; Fisher's direct
      probability test). The bleb wall also became significantly thicker during stage
      IIIa/IIIb infections (P = 0.003). After infection, intraocular pressure (IOP)
      increased significantly for all cases but was no different in the three subgroups
      (i.e. stage I, stage II, and stage IIIa/IIIb bleb infections). Multiple logistic
      regression analysis revealed that a stage III infection was significantly
      associated with a poor outcome for the bleb. CONCLUSIONS: This study revealed
      that the filtering bleb became smaller, both tangentially and circumferentially,
      and thicker, after stage III infections than after stage I or II infections.

PMID- 26220821
TI  - Modification in the properties of paper by using cellulase-free xylanase produced
      from alkalophilic Cellulosimicrobium cellulans CKMX1 in biobleaching of wheat
      straw pulp.
AB  - Alkalophilic Cellulosimicrobium cellulans CKMX1 isolated from mushroom compost is
      an actinomycete that produces industrially important and environmentally safer
      thermostable cellulase-free xylanase, which is used in the pulp and paper
      industry as an alternative to the use of toxic chlorinated compounds. Strain
      CKMX1 was previously characterized by metabolic fingerprinting, whole-cell fatty
      acids methyl ester analysis, and 16S rDNA and was found to be C. cellulans CKMX1.
      Crude enzyme (1027.65 U/g DBP) produced by C. cellulans CKMX1, having pH and
      temperature optima of 8.0 and 60  degrees C, respectively, in solid state
      fermentation of apple pomace, was used in the production of bleached wheat straw
      pulp. Pretreatment with xylanase at a dose of 5 U/g after pulping decreased pulp
      kappa points by 1.4 as compared with the control. Prebleaching with a xylanase
      dose of 5 U/g pulp reduced the chlorine charge by 12.5%, increased the final
      brightness points by approximately 1.42% ISO, and improved the pulp strength
      properties. Xylanase could be substituted for alkali extraction in C-Ep-D
      sequence and used for treating chemically bleached pulp, resulting in bleached
      pulp with higher strength properties. Modification of bleached pulp with 5 U of
      enzyme/g increased pulp whiteness and breaking length by 1.03% and 60 m,
      respectively; decreased tear factor of pulp by 7.29%; increased bulk weight by
      3.99%, as compared with the original pulp. Reducing sugars and UV-absorbing
      lignin-derived compound values were considerably higher in xylanase-treated
      samples. Cellulosimicrobium cellulans CKMX1 has a potential application in the
      pulp and paper industries. 

PMID- 26220822
TI  - Continuous microfluidic fabrication of synthetic asymmetric vesicles.
AB  - We report on a novel microfluidic strategy for the continuous fabrication of
      monodisperse asymmetric vesicles with customized membrane composition, size, and
      luminal content. The microfluidic device encompasses a triangular post region and
      two flow-focusing regions. The major steps involved in the vesicle fabrication
      process include: (1) forming highly uniform water emulsions in an oil/inner
      leaflet-lipid solution, (2) replacing the inner-leaflet-lipid solution with an
      outer-leaflet-lipid solution inside the microchannel network, (3) forming water
      in-oil-in-water double emulsions, and (4) extracting excess oil/outer-leaflet
      lipid solution from the double emulsions. Bilayer membrane asymmetry and
      unilamellarity are evaluated using a fluorescence quenching assay and a
      transmembrane protein insertion assay, respectively. Our approach addresses many
      of the deficiencies found in existing technologies for building vesicles, and
      yields strong membrane asymmetry. The ability to create and sustain membrane
      asymmetry is an important feature, as it is a characteristic of nearly all
      natural membranes. Over 80% of the vesicles remain stable for at least 6 weeks
      and the membrane asymmetry is maintained for over 30 hours. The asymmetric
      vesicles built using this strategy are collected off-chip and hold the potential
      to be used as model systems in membrane biology or as vehicles for drug delivery.

PMID- 26220823
TI  - Matching two independent cohorts validates DPH1 as a gene responsible for
      autosomal recessive intellectual disability with short stature, craniofacial, and
      ectodermal anomalies.
AB  - Recently, Alazami et al. (2015) identified 33 putative candidate disease genes
      for neurogenetic disorders. One such gene was DPH1, in which a homozygous
      missense mutation was associated with a 3C syndrome-like phenotype in four
      patients from a single extended family. Here, we report a second homozygous
      missense variant in DPH1, seen in four members of a founder population, and
      associated with a phenotype initially reminiscent of Sensenbrenner syndrome. This
      postpublication "match" validates DPH1 as a gene underlying syndromic
      intellectual disability with short stature and craniofacial and ectodermal
      anomalies, reminiscent of, but distinct from, 3C and Sensenbrenner syndromes.
      This validation took several years after the independent discoveries due to the
      absence of effective methods for sharing both candidate phenotype and genotype
      data between investigators. Sharing of data via Web-based anonymous data exchange
      servers will play an increasingly important role toward more efficient
      identification of the molecular basis for rare Mendelian disorders. 

PMID- 26220824
TI  - Bone Marrow Stress Decreases Osteogenic Progenitors.
AB  - Age-related bone loss may be a result of declining levels of stem cells in the
      bone marrow. Using the Col2.3Deltatk (DTK) transgenic mouse, osteoblast depletion
      was used as a source of marrow stress in order to investigate the effects of
      aging on osteogenic progenitors which reside in the marrow space. Five-month-old
      DTK mice were treated with one or two cycles of ganciclovir to conditionally
      ablate differentiated osteoblasts, whereas controls were saline-treated.
      Treatment cycles were two weeks in length followed by four weeks of recovery. All
      animals were sacrificed at 8 months of age; bone marrow stromal cells (BMSCs)
      were harvested for cell culture and whole bones were excised for bone quality
      assessment. Colony-forming unit (CFU) assays were conducted to investigate the
      osteogenic potential of BMSC in vitro, and RNA was extracted to assess the
      expression of osteoblastic genes. Bone quality assessments included bone
      histomorphometry, TRAP staining, microcomputed tomography, and biomechanical
      testing. Osteoblast depletion decreased CFU-F (fibroblast), CFU-ALP (alkaline
      phosphatase), and CFU-VK (von Kossa) counts and BMSC osteogenic capacity in cell
      culture. Ex vivo, there were no differences in bone mineral density of vertebrae
      or femurs between treatment groups. Histology showed a decrease in bone volume
      and bone connectivity with repeated osteoblast depletion; however, this was
      accompanied by an increase in bone formation rate. There were no notable
      differences in osteoclast parameters or observed bone marrow adiposity. We have
      developed a model that uses bone marrow stress to mimic age-related decrease in
      osteogenic progenitors. Our data suggest that the number of healthy BMSCs and
      their osteogenic potential decline with repeated osteoblast depletion. However,
      activity of the remaining osteoblasts increases to compensate for this loss in
      progenitor osteogenic potential.

PMID- 26220825
TI  - Cellulose Dissolution and In Situ Grafting in a Reversible System using an
      Organocatalyst and Carbon Dioxide.
AB  - Cellulose is a promising renewable material, but cannot easily be processed
      homogeneously owing to the stiffness of the molecules and the dense packing of
      its chains, due to intermolecular hydrogen bonds. Cellulose processability can be
      improved by chemical modification. The reversible reaction of cellulose with
      carbon dioxide in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) allows
      dissolution of cellulose in dimethyl sulfoxide (DMSO). This DMSO solution is an
      effective medium for grafting L-lactide (LLA) from cellulose by ring-opening
      polymerization (ROP) under mild conditions, allowing to prepare cellulose-graft
      poly(L-lactide) co-polymers with a molar substitution (MSPLLA ) of poly(L
      lactide) in the range of 0.37-5.32, at 80  degrees C. This makes DBU not only an
      important reagent to achieve cellulose dissolution, but it also acts as
      organocatalyst for the subsequent ring-opening polymerization process.
      Characterization of the structure and thermal properties of the co-polymers by a
      variety of techniques reveals that they have a single glass-transition
      temperature (Tg ), which decreases with increasing MSPLLA . Thus, the
      modification results in a transformation of the originally semirigid cellulose
      into a thermoplastic material with tunable Tg . The carbon dioxide dissolution
      strategy is an efficient platform for cellulose derivatization by homogeneous
      organocatalysis.

PMID- 26220826
TI  - Ovarian reserve in women of late reproductive age by the method of treatment of
      PCOS.
AB  - BACKGROUND: The prevalence of polycystic ovarian syndrome (PCOS) particularly is
      increased in adolescents. Very few longitudinal follow-up for assessment of
      ovarian reserve in women of late reproductive age with previously confirmed PCOS
      have been conducted, especially after its diagnosis and treatment in adolescence.
      OBJECTIVE: The aim of the present study was to compare of the ovarian reserve of
      the women of late reproductive age by the method of treatment of PCOS in
      adolescence. MATERIALS AND METHODS: This cross sectional study in an unselected
      population was conducted from January to June 2014. A total of 123 women of late
      reproductive age were included. They had been diagnosed with PCOS between 1984
      and 1990 when they were 13-18 yr. From these, first group of the study was
      consisted of 67 participants who underwent conservative treatment with
      antiandrogens and combined oral contraceptives and second group of the study was
      consisted of 56 participants after surgery (34-bilateral ovarian drilling and 22-
      ovarian wedge resection). At the time of investigation patients were 35-45 yr.
      The participants were collected via analysis of histories at primary diagnosis of
      PCOS in adolescence and at the time of the investigation analyses of reproductive
      hormones were conducted. Data were compared between the groups. RESULTS: After
      conservative treatment PCOS women had higher levels of anti- mullerian hormone
      and lower follicle-stimulating hormone levels (p=0.02 and p=0.04, respectively).
      The number of antral follicles and mean ovarian volume were significantly greater
      also, than in women who underwent surgical treatment (p=0.03 and p=0.04,
      respectively). CONCLUSION: Our data suggest that PCOS patients who underwent
      conservative treatment have the better ovarian reserve than women who underwent
      surgical treatment of PCOS in adolescence.

PMID- 26220827
TI  - Clinical Significance of EphB4 and EphB6 Expression in Human Malignant and Benign
      Thyroid Lesions.
AB  - Ephrin receptors (Ephs) are frequently overexpressed in a wide variety of human
      malignant tumors, being associated with tumor growth, invasion, angiogenesis and
      metastasis. The present study aimed to evaluate the clinical significance of
      EphB4 and EphB6 protein expression in human malignant and benign thyroid lesions.
      EphB4 and EphB6 protein expression was assessed immunohistochemically on paraffin
      embedded thyroid tissues obtained from 127 patients with benign (n = 71) and
      malignant (n = 56) thyroid lesions. Enhanced EphB4 and EphB6 expression was more
      frequently observed in malignant compared to benign thyroid lesions (p = 0.0508
      and p = 0.0006, respectively). EphB4 and EphB6 expression also provided a
      distinct discrimination between papillary carcinoma and hyperplastic nodules (p =
      0.0302 and p = 0.0013, respectively). In malignant thyroid lesions, enhanced
      EphB4 expression was significantly associated with larger tumor size (p =
      0.0366). Enhanced EphB6 expression was significantly associated with larger tumor
      size (p = 0.0366), the presence of lymph node metastases (p = 0.0023), the
      presence of capsular (p = 0.0038), lymphatic (p = 0.0053) and vascular invasion
      (p = 0.0018) and increased risk of recurrence rate (p = 0.0038). The present
      study supported evidence that EphB4 and mainly EphB6 may participate in the
      malignant thyroid transformation, reinforcing their utility as useful biomarkers
      and possible therapeutic targets in this type of neoplasia.

PMID- 26220828
TI  - Long-term air pollution exposure and lung function in 15 year-old adolescents
      living in an urban and rural area in Germany: The GINIplus and LISAplus cohorts.
AB  - INTRODUCTION: The impact of outdoor air pollution exposure on long-term lung
      development and potential periods of increased lung susceptibility remain
      unknown. This study assessed associations between early-life and current
      residential exposure to air pollution and lung function at 15-years of age in two
      German birth cohorts. METHODS: Fifteen year-old participants living in an urban
      and rural area in Germany underwent spirometry before and after bronchodilation
      (N=2266). Annual average (long-term) exposure to nitrogen dioxide (NO(2)),
      particles with aerodynamic diameters less than 2.5 MUg/m(3) (PM2.5) mass and less
      than 10 MUg/m(3) (PM(10)) mass, PM(2.5) absorbance and ozone were estimated to
      each participant's birth-, 10- and 15-year home address using land-use regression
      and kriging (ozone only) modelling. Associations between lung function variables
      and long-term pollutant concentrations were assessed using linear regression
      models adjusted for host and environmental covariates and recent short-term air
      pollution exposures. RESULTS: Long-term air pollution concentrations assessed to
      the birth-, 10- and 15-year home addresses were not associated with lung function
      variables, before and after bronchodilation, in the complete or study area
      specific populations. However, several lung function variables were negatively
      associated with long-term NO2 concentrations among asthmatics. For example, NO(2)
      estimated to the 15-year home address was associated with the ratio of forced
      expiratory volume in one second to forced vital capacity (FEV(1)/FVC) and the
      mean flow rate between 25% and 75% of FVC (-3.5%, 95% confidence interval [-6.0, 
      1.0] and -297.4 ml/s [-592.6, -2.1] per 5.9 MUg/m(3) increase in NO(2),
      respectively). Nearly all effect estimates for the associations between the short
      term PM(2.5) mass, PM(10) mass and ozone concentrations and the lung function
      variables were negative in the complete population. CONCLUSIONS: Early-life and
      current long-term air pollution exposures and lung function at the age of 15
      years were not associated in the complete study population. Asthmatics may
      represent a vulnerable group.

PMID- 26220829
TI  - Evaluating the Validity of Caffeine Use Disorder.
AB  - Caffeine use disorder is included in the conditions for further study section of
      the DSM-5. Caffeine's profile of neurobiological, behavioral, and clinical
      effects is similar to other common substances that humans use recreationally.
      Extant data suggest that a clinically meaningful addictive disorder develops in
      some regular caffeine users, but this literature is incomplete and not yet
      sufficient to determine if and how best to define and treat caffeine use
      disorder. An overview of the literature relevant to determining the clinical
      importance of problematic caffeine use is followed by discussion of potential
      concerns and benefits associated with its classification as a mental disorder.
      Concerns about overdiagnosis and trivialization of other psychiatric syndromes
      are weighed against the public health benefits of increased awareness and
      development of interventions targeting problematic caffeine use. This discussion
      includes consideration of alternative diagnostic approaches, improvement of
      assessment practices, and the need for additional clinical and epidemiological
      research. 

PMID- 26220831
TI  - Pits (and Plums?) in the Mire of Medical Talk Shows.

PMID- 26220830
TI  - Lhx9 gene expression during early limb development in mice requires the FGF
      signalling pathway.
AB  - Lhx9 is a member of the LIM-homeodomain gene family necessary for the correct
      development of many organs including gonads, limbs, heart and the nervous system.
      In the context of limb development, Lhx9 has been implicated as an integrator for
      Fibroblast growth factor (FGF) and Sonic hedgehog (Shh) signalling required for
      proximal-distal (PD) and anterior-posterior (AP) development of the limb. Three
      splice variants of the Lhx9 transcript are expressed during development, two of
      which are predicted to act in a dominant negative fashion, competing with the DNA
      binding version of Lhx9 for binding to cofactors via the LIM-domain. We examined
      the expression pattern for the three alternative splice forms of Lhx9; Lhx9alpha,
      Lhx9beta and Lhx9c during early limb development. We have found that of the three
      Lhx9 isoforms, only Lhx9alpha and Lhx9c (intact homeodomain) are expressed during
      early limb development, each with their own distinct expression pattern.
      Additionally we determined that Lhx9 expression overlaps with FGF10 expression in
      the developing limb bud mesenchyme. Limb bud explant cultures, in the presence of
      signalling pathway inhibitors, also indicated that Lhx9 mRNA expression in the
      limb bud was dependent on FGF signalling. 

PMID- 26220832
TI  - Screening and Identification of Inhibitors Against Glutathione Synthetase, A
      Potential Drug Target of Plasmodium falciparum.
AB  - Malaria is the world's most fatal disease - causing up to 2.7 million deaths
      annually all over the world. The ability of organisms to develop resistance
      against existing antimalarial drugs exacerbates the problem. There is a clear cut
      need for more effective, affordable and accessible drugs that act by novel modes
      of action. Glutathione synthetase (GS) from Plasmodium falciparum represents an
      important potential drug target due to its defensive role; hence ceasing the
      respective metabolic step will destroy the parasite. A three dimensional model of
      Plasmodium GS was constructed by de novo modelling method and potential GS
      inhibitors were identified from a library of glutathione (GSH) analogues
      retrieved from Ligand-info database and filtered using Lipinski and ADME rules.
      Two common feature pharmacophore models were generated from the individual
      inhibitor clusters to provide insight into the key pharmacophore features that
      are crucial for the GS inhibition. Molecular docking of selective compounds into
      the predicted GS binding site revealed that the compound CMBMB was the best GS
      inhibitor when compared to the standard reference Chloroquine (CQ). This was
      taken as indicating that CMBMB was the best effective and safest drug against P.
      falciparum. 

PMID- 26220833
TI  - Introduction to special issue on glaucomatous optic neuropathy: In vivo models
      and techniques.

PMID- 26220835
TI  - Collisional excitation of CH(X2Pi) by He: new ab initio potential energy surfaces
      and scattering calculations.
AB  - We present a new set of potential energy surfaces (PESs) for the CH(X(2)Pi)-He
      van der Waals system. Ab initio calculations of the CH-He PES were carried out
      using the open-shell single- and double-excitation coupled cluster approach with
      non-iterative perturbational treatment of triple excitations [RCCSD(T)]. The
      augmented correlation-consistent polarized valence quadruple-zeta (aug-cc-pVQZ)
      basis set was employed augmented by mid-bond functions. Integral cross sections
      for the rotational excitation in CH-He collisions were calculated using the new
      PES and compared with available experimental results. The newly constructed PES
      reproduces the available experimental results for CH(X(2)Pi, v = 0)-He collisions
      better than any previously available PES. Differential cross sections (DCS) are
      presented for the first time for this system and discussed within the context of
      rotational rainbows. Finally, our work provides the first rate thermal
      coefficients for this system that are crucially needed for astrochemical
      modelling and future anticipated experiments in CH(X(2)Pi)-He collisions. 

PMID- 26220834
TI  - Idiopathic preretinal glia in aging and age-related macular degeneration.
AB  - During analysis of glia in wholemount aged human retinas, frequent projections
      onto the vitreal surface of the inner limiting membrane (ILM) were noted. The
      present study characterized these preretinal glial structures. The amount of
      glial cells on the vitreal side of the ILM was compared between eyes with age
      related macular degeneration (AMD) and age-matched control eyes. Retinal
      wholemounts were stained for markers of retinal astrocytes and activated Muller
      cells (glial fibrillary acidic protein, GFAP), Muller cells (vimentin, glutamine
      synthetase) and microglia/hyalocytes (IBA-1). Retinal vessels were labeled with
      UEA lectin. Images were collected using a Zeiss LSM 710 confocal microscope.
      Retinas were then cryopreserved. Laminin labeling of cryosections determined the
      location of glial structures in relation to the ILM. All retinas investigated
      herein had varied amounts of preretinal glia. These glial structures were
      classified into three groups based on size: sprouts, blooms, and membranes. The
      simplest of the glial structures observed were focal sprouts of singular GFAP
      positive cells or processes on the vitreal surface of the ILM. The intermediate
      structures observed, glial blooms, were created by multiple cells/processes
      exiting from a single point and extending along the vitreoretinal surface. The
      most extensive structures, glial membranes, consisted of compact networks of
      cells and processes. Preretinal glia were observed in all areas of the retina but
      they were most prominent over large vessels. While all glial blooms and membranes
      contained vimentin and GFAP-positive cells, these proteins did not always co
      localize. Many areas had no preretinal GFAP but had numerous vimentin only glial
      sprouts. In double labeled glial sprouts, vimentin staining extended beyond that
      of GFAP. Hyalocytes and microglia were detected along with glial sprouts, blooms,
      and membranes. They did not, however, concentrate in the retina below these
      structures. Cross sectional analysis identified small breaks in the ILM above
      large retinal vessels through which glial cells exited the retina. Preretinal
      glial structures of varied sizes are a common occurrence in aged retinas and, in
      most cases, are subclinical. While all retinal glia are found in blooms, vimentin
      labeling suggests that Muller cells form the leading edge. All retinas
      investigated from eyes with active choroidal neovascularization (CNV) had
      extensive glial membranes on the vitreal surface of the ILM. Although these
      structures may be benign, they may exert traction on the retina as they spread
      along the vitreoretinal interface. In cases with CNV, glial cells in the vitreous
      could bind intravitreally injected anti-vascular endothelial growth factor. These
      preretinal glial structures indicate the remodeling of both astrocytes and Muller
      cells in aged retinas, in particular those with advanced AMD.

PMID- 26220836
TI  - Caenogastropod mitogenomics.
AB  - In order to further resolve the phylogenetic relationships within
      Caenogastropoda, the complete mitochondrial (mt) genomes of Cochlostoma hidalgoi
      (Cyclophoroidea), Naticarius hebraeus (Naticoidea), Galeodea echinophora
      (Tonnoidea), and Columbella adansoni (Buccinoidea), and the partial mt genome of
      Erosaria spurca (Cypraeoidea) were sequenced. All newly determined mt genomes
      conformed to the consensus gene order of caenogastropods, except that of C.
      hidalgoi, which differed in the relative positions of the trnD, trnQ, trnG, trnY,
      and trnT genes. Phylogenetic reconstruction of the caenogastropod tree was
      performed using probabilistic methods and based on the deduced amino acid
      sequences of concatenated mt protein coding genes. The reconstructed phylogeny
      recovered Architaenioglossa (superfamilies Cyclophoroidea, Ampullarioidea, and
      Viviparoidea) as a grade. The monophyly of Sorbeoconcha (all caenogastropods but
      Architaenioglossa) was supported by most but not all phylogenetic analyses
      (excluding Vermetoidea, which has a long branch). The relative phylogenetic
      position of Cerithioidea with respect to Hypsogastropoda remains unresolved. The
      monophyly of Hypsogastropoda (without Vermetoidea) is strongly supported. Within
      this clade, Littorinimorpha should be considered a grade. Several superfamilies
      (Abyssochrysoidea, Rissooidea, Truncatelloidea, and Naticoidea) branched off
      successively before a siphonate clade (Stromboidea, Cypraeoidea, Tonnoidea,
      Neogastropoda), which is strongly supported. The relative phylogenetic position
      of Vermetoidea could not be determined due to long-branch attraction artifacts.
      The superfamily Tonnoidea was recovered within Neogastropoda, which questions the
      monophyly of the latter as traditionally defined. The polyphyly of Muricoidea
      could be tentatively resolved excluding the families Volutidae and Babyloniidae,
      which would imply raising them to the rank of superfamilies. 

PMID- 26220837
TI  - Islands within islands: Diversification of tailless whip spiders (Amblypygi,
      Phrynus) in Caribbean caves.
AB  - Islands have played a key role in understanding species formation ever since
      Darwin's work on the Galapagos and Wallace's work in the Malay Archipelago. Like
      oceanic islands, habitat 'islands', such as mountaintops and caves similarly may
      drive diversification. Here we examine patterns of diversification in the
      tailless whip spider genus Phrynus Larmarck, 1809 (Amblypygida: Phrynidae) a
      system that shows evidence of diversification under the influence of 'islands
      within islands'. We estimate phylogeographic history and measure genetic
      diversity among representatives of three nominal Phrynus species from epigean and
      cave systems of Puerto Rico and nearby islands. Data from five loci
      (mitochondrial 12S, 16S, Cox1; nuclear H3, 28S) were used to generate
      phylogenetic hypotheses and to assess species monophyly and phylogeographic
      relationships. Genetic divergences and population limits were estimated and
      assessed using the Geneious barcoding plugin and the genealogical sorting index.
      We find that mtDNA sequence divergences within each of the three Phrynus species
      range between 15% and 20%. Genetic divergence is structured at three spatial
      scales: among islands in a manner consistent with the GAARlandia hypothesis,
      among bedrock formations within Puerto Rico, and among caves within these
      formations. Every isolated cave system contains a unique mtDNA genetic lineage of
      Phrynus, with divergence among cave systems far exceeding that within. In some
      localities epigean specimens nest among cave taxa, in others caves are
      monophyletic. Remarkably, clades that show up to 20% mtDNA sequence divergence
      show little or no variation in the nuclear markers. We interpret this pattern as
      resulting from extreme conservation of our nuclear markers rather than male sex
      biased dispersal, based on high conservation of 28S and H3 between our
      individuals and other amblypygid genera that are restricted to Africa. While this
      study includes but a tiny fraction of Caribbean caves, our findings suggest
      Phrynus may be much more diverse than hitherto thought, at least in terms of
      mtDNA diversity, and that the arthropod fauna of caves may represent a dimension
      of biodiversity that is yet to be discovered in the Caribbean biodiversity
      hotspot. 

PMID- 26220838
TI  - Dating the origin of hepatitis B virus reveals higher substitution rate and
      adaptation on the branch leading to F/H genotypes.
AB  - The evolution of hepatitis B virus (HBV), particularly its origins and
      evolutionary timescale, has been the subject of debate. Three major scenarios
      have been proposed, variously placing the origin of HBV in humans and great apes
      from some million years to only a few thousand years ago (ka). To compare these
      scenarios, we analyzed 105 full-length HBV genome sequences from all major
      genotypes sampled globally. We found a high correlation between the demographic
      histories of HBV and humans, as well as coincidence in the times of origin of
      specific subgenotypes with human migrations giving rise to their host indigenous
      populations. Together with phylogenetic evidence, this suggests that HBV has co
      expanded with modern humans. Based on the co-expansion, we conducted a Bayesian
      dating analysis to estimate a precise evolutionary timescale for HBV. Five
      calibrations were used at the origins of F/H genotypes, D4, C3 and B6 from
      respective indigenous populations in the Pacific and Arctic and A5 from Haiti.
      The estimated time for the origin of HBV was 34.1ka (95% highest posterior
      density interval 27.6-41.3ka), coinciding with the dispersal of modern non
      African humans. Our study, the first to use full-length HBV sequences, places a
      precise timescale on the HBV epidemic and also shows that the "branching paradox"
      of the more divergent genotypes F/H from Amerindians is due to an accelerated
      substitution rate, probably driven by positive selection. This may explain
      previously observed differences in the natural history of HBV between genotypes
      F1 and A2, B1, and D. 

PMID- 26220839
TI  - Algal endosymbionts in European Hydra strains reflect multiple origins of the
      zoochlorella symbiosis.
AB  - Symbiotic associations are of broad significance in evolution and biodiversity.
      Green Hydra is a classic example of endosymbiosis. In its gastrodermal
      myoepithelial cells it harbors endosymbiotic unicellular green algae, most
      commonly from the genus Chlorella. We reconstructed the phylogeny of cultured
      algal endosymbionts isolated and maintained in laboratory conditions for years
      from green Hydra strains collected from four different geographical sites within
      Croatia, one from Germany and one from Israel. Nuclear (18S rDNA, ITS region) and
      chloroplast markers (16S, rbcL) for maximum likelihood phylogenetic analyses were
      used. We focused on investigating the positions of these algal endosymbiotic
      strains within the chlorophyte lineage. Molecular analyses established that
      different genera and species of unicellular green algae are present as
      endosymbionts in green Hydra, showing that endosymbiotic algae growing within
      green Hydra sampled from four Croatian localities are not monophyletic. Our
      results indicate that the intracellular algal endosymbionts of green Hydra have
      become established several times independently in evolution. 

PMID- 26220840
TI  - Evolutionary dynamics of a cycad obligate pollination mutualism - Pattern and
      process in extant Macrozamia cycads and their specialist thrips pollinators.
AB  - Obligate pollination mutualisms are rare and few have been investigated deeply.
      This paper focuses on one such mutualism involving thrips in the genus
      Cycadothrips that pollinate cycads in the genus Macrozamia. Both represent old
      lineages relative to insects and plants generally, are endemic to Australia, and
      are mutually co-dependent. The phylogenetic analyses presented here demonstrate
      that the pollinator is much more diverse than previously considered, with each
      pollinator lineage being extremely specific to between one and three host species
      where these latter share part of their distribution. The new species diversity we
      demonstrate in Cycadothrips all presently falls under the species name C.
      chadwicki, and these different lineages diversified during two periods. An older
      divergence, beginning 7.3Mya (4.4-11.1, 95% HPD), resulted in three major
      lineages, and then further diversification within each of these three lineages
      took place at most 1.1Mya (0.6-1.8, 95% HPD). These divergence estimates
      correspond to times when aridification was increasing in Australia, suggesting
      that population fragmentation following climatic change has played a significant
      role in the evolutionary history of Cycadothrips and Macrozamia. This means that
      co-diversification of the host and pollinator in allopatry appears to be the
      dominant process affecting species diversity. Host switching is also clearly
      evident in the discrepancy between the divergence times of the C. chadwicki
      lineage and C. albrechti, about 10.8Mya (6.0-17.1, 95% HPD), and their hosts, at
      about 1.1Mya (0.2-3.4Mya, 95% HPD), in that the pollinator split pre-dates the
      origin of the associated host species of each. These results add to the body of
      evidence that the evolutionary processes important in obligate pollinator
      mutualisms are more varied than previously assumed. 

PMID- 26220841
TI  - Phylogeography of the land snail genus Circassina (Gastropoda: Hygromiidae)
      implies multiple Pleistocene refugia in the western Caucasus region.
AB  - The phylogeny and historical biogeography of the Caucasian land snail genus
      Circassina was reconstructed using multilocus amplified fragment length
      polymorphism (AFLP) data and mitochondrial DNA sequences. Diversification within
      the group started with a divergence of populations from the western Lesser
      Caucasus from those of the Greater Caucasus during the late Miocene. Distinct
      AFLP clusters and major mitochondrial clades separated by long internal branches
      lend evidence to the hypothesis of separate glacial refuges in the Lesser and
      Greater Caucasus during the Pleistocene. High genetic distances across low
      geographic distances and admixture analysis revealed a phylogeographic boundary
      running through the Colchis lowlands, which may have been established and
      maintained in part by repeated transgressions of the Black Sea during the
      Pleistocene and Holocene. Localities in Ciscaucasia were probably colonised
      through long-distance dispersal across the main ridge of the Greater Caucasus.
      The phylogeny implies multiple independent losses of accessory genital organs,
      i.e. dart sac and mucus glands, within Circassina. None of the anatomically
      defined (sub-) species distinguished so far is monophyletic and there is gene
      flow between the two main population groups across the Colchis lowlands. Thus, we
      propose to classify these population groups as subspecies of a single species. 

PMID- 26220842
TI  - Three-dimensional imaging of microvasculature in the rat spinal cord following
      injury.
AB  - Research studies on the three-dimensional (3D) morphological alterations of the
      spinal cord microvasculature after injury provide insight into the pathology of
      spinal cord injury (SCI). Knowledge in this field has been hampered in the past
      by imaging technologies that provided only two-dimensional (2D) information on
      the vascular reactions to trauma. The aim of our study is to investigate the 3D
      microstructural changes of the rat spinal cord microvasculature on day 1 post
      injury using synchrotron radiation micro-tomography (SRMUCT). This technology
      provides high-resolution 3D images of microvasculature in both normal and injured
      spinal cords, and the smallest vessel detected is approximately 7.4 MUm.
      Moreover, we optimized the 3D vascular visualization with color coding and
      accurately calculated quantitative changes in vascular architecture after SCI.
      Compared to the control spinal cord, the damaged spinal cord vessel numbers
      decreased significantly following injury. Furthermore, the area of injury did not
      remain concentrated at the epicenter; rather, the signs of damage expanded
      rostrally and caudally along the spinal cord in 3D. The observed pathological
      changes were also confirmed by histological tests. These results demonstrate that
      SRMUCT is an effective technology platform for imaging pathological changes in
      small arteries in neurovascular disease and for evaluating therapeutic
      interventions. 

PMID- 26220843
TI  - [Not Available].

PMID- 26220844
TI  - Predictive value of STMN1 gene promoter polymorphism (-2166T>C) in patients with
      advanced NSCLC treated with the combination of platinum compounds and
      vinorelbine.
AB  - PURPOSE: The combination of platinum compounds and vinorelbine is often used as a
      first-line treatment in patients with locally advanced or metastatic non-small
      cell lung cancer (NSCLC), without activating EGFR mutations and ALK
      rearrangement. Unfortunately, less than half of the patients benefit from
      chemotherapy. Moreover, majority of patients are exposed to a number of side
      effects of chemotherapy. Stathmin-1 (STMN1, oncoprotein 18) affects significantly
      microtubule dynamics and formation of the mitotic spindle. Therefore, the change
      in the STMN1 gene may be a potential predictive factor of response to treatment
      regimens containing a cytostatics-disrupting microtubule dynamics (vinca
      alkaloids and taxoids). The aim of the study was to determine the relationship
      between a single nucleotide polymorphism (SNP) of the promoter of STMN1 gene 
      2166T>C) and the effectiveness of chemotherapy based on platinum compounds and
      vinorelbine in patients with NSCLC. METHODS: The investigated population
      consisted of 110 locally advanced or metastatic NSCLC patients treated with first
      line chemotherapy, based on platinum compounds and vinorelbine. SNP was
      determined by SNaPshotTM PCR in DNA isolated from peripheral blood leukocytes.
      RESULTS: The median progression-free survival (PFS) was significantly shorter in
      carriers of TT genotype of the STMN1 gene compared with patients with CC or CT
      genotypes (2.75 vs. 6.5 months; p = 0.0033; HR 5.91, 95% CI 1.81-19.33).
      Evaluated SNP did not significantly affect the response to treatment and the
      overall survival of the patients. CONCLUSION: Rare TT genotype of STMN1 gene may
      be an unfavorable predictive factor of chemotherapy based on platinum compounds
      and vinorelbine, in patients with NSCLC.

PMID- 26220845
TI  - S-1 and irinotecan with or without bevacizumab versus 5-fluorouracil and
      leucovorin plus oxaliplatin with or without bevacizumab in metastatic colorectal
      cancer: a pooled analysis of four phase II studies.
AB  - PURPOSE: S-1, a novel oral prodrug of 5-fluorouracil (5-FU), and irinotecan with
      or without bevacizumab is known to be effective in metastatic colorectal cancer
      (mCRC). However, it is not clear whether S-1 and irinotecan confers benefits
      compared to 5-FU and leucovorin plus oxaliplatin (FOLFOX) in patients with mCRC.
      Our aim was to compare the efficacy and safety of these regimens. METHODS: We
      analyzed 187 patients with previously untreated mCRC who were enrolled in four
      phase II studies: SIR (S-1 and irinotecan, n = 40), SIRB (S-1 and irinotecan with
      bevacizumab, n = 51), FOLFOX (5-FU and leucovorin plus oxaliplatin, n = 46), and
      STOX (stop-and-go strategy of modified FOLFOX-6 with bevacizumab, n = 50). We
      evaluated efficacy and safety between SIR/SIRB and FOLFOX/STOX. RESULTS: Baseline
      characteristics were similar in the two groups composed of SIR/SIRB (n = 91) and
      FOLFOX/STOX (n = 96). The overall response rates were not significantly different
      between the two groups (65% in SIR/SIRB vs. 52% in FOLFOX/STOX, p = 0.125). The
      median progression-free survival was 10.9 months in SIR/SIRB versus 12.1 months
      in FOLFOX/STOX (p = 0.59). The median overall survival was 27.3 months in
      SIR/SIRB versus 26.8 months in FOLFOX/STOX (p = 0.97). Gastrointestinal adverse
      events were the most common toxicities in SIR/SIRB, while neutropenia and sensory
      neuropathy were the most common toxicities in FOLFOX/STOX. CONCLUSIONS: S-1 and
      irinotecan with or without bevacizumab was well tolerated and showed similar
      response rates and survival compared to the FOLFOX regimen. This combination
      should be considered as an experimental first-line treatment for mCRC.

PMID- 26220846
TI  - A phase I/II study of fixed-dose-rate gemcitabine and S-1 with concurrent
      radiotherapy for locally advanced pancreatic cancer.
AB  - PURPOSE: This study was conducted to identify the maximum-tolerated dose (MTD) of
      fixed-dose-rate gemcitabine (FDR-gem) administered concurrently with S-1 and
      radical radiation for locally advanced pancreatic cancer (LAPC) and to provide
      efficacy and safety data. METHODS: Patients with unrespectable pancreatic cancer
      confined to the pancreatic region were treated with FDR-gem (300-400 mg/m(2), 5
      mg/m(2)/min) on days 1, 8, 22, and 29 and 60 mg/m(2) of S-1 orally on days 1-14,
      22-35. A total radiation dose of 50.4 Gy (1.8 Gy/day, 28 fractions) was delivered
      concurrently. RESULTS: Twenty-five patients were enrolled; all were evaluable for
      toxicity assessment. In phase I, eight patients were treated in sequential
      cohorts of three to five patients per dose level. The MTD was reached at level 2,
      and dose-limiting toxicities were neutropenia and thrombocytopenia. The
      recommended doses were 300 mg/m(2) of gemcitabine and 60 mg/m(2) of S-1 daily.
      The overall response rate was 25% and disease control rate (partial response plus
      stable disease) was 92%. The progression-free survival was 11.0 months. The
      median overall survival and 1-year survival rates were 16.0 months and 73%,
      respectively. CONCLUSION: The combination of FDR-gem and S-1 with radiation is a
      feasible regimen that shows favorable antitumor activity with an acceptable
      safety profile in patients with LAPC.

PMID- 26220847
TI  - Facile and Scalable Preparation of Graphene Oxide-Based Magnetic Hybrids for Fast
      and Highly Efficient Removal of Organic Dyes.
AB  - This study reports the facile preparation and the dye removal efficiency of
      nanohybrids composed of graphene oxide (GO) and Fe3O4 nanoparticles with various
      geometrical structures. In comparison to previously reported GO/Fe3O4 composites
      prepared through the one-pot, in situ deposition of Fe3O4 nanoparticles, the
      GO/Fe3O4 nanohybrids reported here were obtained by taking advantage of the
      physical affinities between sulfonated GO and Fe3O4 nanoparticles, which allows
      tuning the dimensions and geometries of Fe3O4 nanoparticles in order to decrease
      their contact area with GO, while still maintaining the magnetic properties of
      the nanohybrids for easy separation and adsorbent recycling. Both the as-prepared
      and regenerated nanohybrids demonstrate a nearly 100% removal rate for methylene
      blue and an impressively high removal rate for Rhodamine B. This study provides
      new insights into the facile and controllable industrial scale fabrication of
      safe and highly efficient GO-based adsorbents for dye or other organic pollutants
      in a wide range of environmental-related applications. 

PMID- 26220848
TI  - Claw length recommendations for dairy cow foot trimming.
AB  - The aim was to describe variation in length of the dorsal hoof wall in contact
      with the dermis for cows on a single farm, and hence, derive minimum appropriate
      claw lengths for routine foot trimming. The hind feet of 68 Holstein-Friesian
      dairy cows were collected post mortem, and the internal structures were
      visualised using x-ray uCT. The internal distance from the proximal limit of the
      wall horn to the distal tip of the dermis was measured from cross-sectional
      sagittal images. A constant was added to allow for a minimum sole thickness of 5
      mm and an average wall thickness of 8 mm. Data were evaluated using descriptive
      statistics and two-level linear regression models with claw nested within cow.
      Based on 219 claws, the recommended dorsal wall length from the proximal limit of
      hoof horn was up to 90 mm for 96 per cent of claws, and the median value was 83
      mm. Dorsal wall length increased by 1 mm per year of age, yet 85 per cent of the
      null model variance remained unexplained. Overtrimming can have severe
      consequences; the authors propose that the minimum recommended claw length stated
      in training materials for all Holstein-Friesian cows should be increased to 90
      mm. 

PMID- 26220850
TI  - Partnering with Indigenous student co-researchers: improving research processes
      and outcomes.
AB  - OBJECTIVE: To examine the contribution of student co-researchers to a community
      based participatory Photovoice investigation of Indigenous children's food
      related lived experience. We examine co-researchers' contributions to the
      research process, their role in knowledge co-generation and dissemination, and
      factors that fostered research partnership with the teenage co-researchers.
      METHODS: High school students attending a First Nation community school in Canada
      were trained as research partners. They contributed to aspects of research
      design, conducted interviews with grades 3 and 4 Photovoice participants, and
      participated in data analysis and the development of a culturally relevant
      photobook. The study was initiated by the community's research committee. It is
      informed by critical consciousness theory and the positive youth development
      framework. RESULTS: Student co-researchers incorporated culturally appropriate
      strategies as they interviewed participants. Co-researchers adopted
      conversational approaches, built rapport by articulating personal and cultural
      connections, and engaged in mentoring and health promotion as they interviewed
      participants. They made critical contributions to dissemination by developing
      photobook content that promoted the importance of traditional foods and the vital
      role of family and community in healthy eating practices. Relationships and
      "dialogic" space were important to building partnership with and promoting
      capacity development among youth co-researchers. CONCLUSIONS: Partnership between
      university researchers and Indigenous student co-researchers holds great promise
      for health promotion in communities. Co-researchers developed research and
      leadership skills, gained understanding of health challenges facing their
      community, and initiated health and cultural promotion through the project's
      Photobook. This investigation supports the powerful potential of student co
      researchers to meaningfully contribute to research processes and to build
      knowledge that is relevant and credible both within and outside of their
      communities. Findings have implications for youth, communities and researchers.

PMID- 26220851
TI  - An endophyte of Picrorhiza kurroa Royle ex. Benth, producing menthol, phenylethyl
      alcohol and 3-hydroxypropionic acid, and other volatile organic compounds.
AB  - An endophytic fungus, PR4 was found in nature associated with the rhizome of
      Picrorhiza kurroa, a high altitude medicinal plant of Kashmir Himalayas. The
      fungus was found to inhibit the growth of several phyto-pathogens by virtue of
      its volatile organic compounds (VOCs). Molecular phylogeny, based on its ITS1
      5.8S-ITS2 ribosomal gene sequence, revealed the identity of the fungus as
      Phomopsis/Diaporthe sp. This endophyte was found to produce a unique array of
      VOCs, particularly, menthol, phenylethyl alcohol, (+)-isomenthol, beta
      phellandrene, beta-bisabolene, limonene, 3-pentanone and 1-pentanol. The
      purification of compounds from the culture broth of PR4 led to the isolation of 3
      hydroxypropionic acid (3-HPA) as a major metabolite. This is the first report of
      a fungal culture producing a combination of biologically and industrially
      important metabolites-menthol, phenylethyl alcohol, and 3-HPA. The investigation
      into the monoterpene biosynthetic pathway of PR4 led to the partial
      characterization of isopiperitenone reductase (ipr) gene, which seems to be
      significantly distinct from the plant homologue. The biosynthesis of plant-like
      metabolites, such as menthol, is of significant academic and industrial
      significance. This study indicates that PR4 is a potential candidate for
      upscaling of menthol, phenylethyl alcohol, and 3-HPA, as well as for
      understanding the menthol/monoterpene biosynthetic pathway in fungi.

PMID- 26220852
TI  - MATERNAL EXPERIENCE OF ABUSE IN CHILDHOOD AND DEPRESSIVE SYMPTOMS IN ADOLESCENT
      AND ADULT OFFSPRING: A 21-YEAR LONGITUDINAL STUDY.
AB  - BACKGROUND: Intergenerational effects of child abuse have been documented, but it
      is unknown whether maternal childhood abuse influences offspring mental health in
      adolescence or adulthood. METHODS: To examine whether maternal experience of
      childhood abuse is associated with depressive symptoms in adolescent and young
      adult offspring, we linked data from two large longitudinal cohorts of women (N =
      8,882) and their offspring (N = 11,402), and we examined three possible pathways
      by which maternal experience of abuse might be associated with offspring
      depressive symptoms: maternal mental health, family characteristics, and
      offspring's own experience of abuse. RESULTS: Offspring of women who experienced
      severe versus no childhood abuse had greater likelihood of high depressive
      symptoms (RR = 1.78, 95% CI = 1.47, 2.16) and persistent high depressive symptoms
      (RR = 2.47, 95% CI = 1.37, 4.44). Maternal mental health accounted for 20.9% and
      offspring's exposure to abuse accounted for 30.3% of the elevated risk of high
      depressive symptoms. Disparities in offspring depressive symptoms by maternal
      abuse exposure were evident at age 12 years and persisted through age 31 years.
      CONCLUSIONS: Findings provide evidence that childhood abuse adversely affects the
      mental health of the victim's offspring well into adulthood. As offspring
      exposure to abuse and maternal mental health accounted for more than 50% of the
      elevated risk of high depressive symptoms among offspring of women who
      experienced abuse, improving maternal mental health and parenting practices may
      reduce offspring risk for depressive symptoms in these families.

PMID- 26220853
TI  - Circadian rest-activity rhythm in individuals at risk for psychosis and bipolar
      disorder.
AB  - BACKGROUND: At-risk mental states (ARMS) are clinical syndromes that are
      associated with higher risk, compared with the general population, for developing
      psychosis and bipolar disorder. Circadian rhythm misalignments have been proposed
      to be part of this early phase of the clinical course. OBJECTIVE: To compare
      circadian rhythm of activity and rest changes between ARMS individuals and a
      healthy control group. METHODS: Forty volunteers of both genders, aged between 13
      and 27years old, participated in this study (n=20 ARMS group, and n=20 healthy
      controls). The ARMS individuals were classified as ultra-high risk for psychosis
      according to the CAARMS (Comprehensive Assessment of At-risk Mental State) or at
      high risk for bipolar disorder according to criteria proposed by Bechdolf and
      colleagues. Participants used an actigraph for fifteen days, kept a sleep diary,
      and completed the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index,
      and a Morningness-Eveningness Questionnaire. RESULTS: Compared with healthy
      volunteers, the ARMS group presented worse sleep quality (P=0.010); longer nap
      durations (P=0.038), shorter wake times (P=0.001), higher total sleep times
      (P=0.011), and shorter activity duration (P=0.021), sleep rhythms were more
      fragmented, the circadian rest-activity rhythms were less synchronized with the
      dark-light cycle and had lower amplitudes of motor activity. CONCLUSION: The
      results suggest alterations in the circadian rest-activity rhythms (and likely in
      sleep-wake cycle patterns) in ARMS individuals compared with healthy controls. It
      is possible that circadian rhythms of activity and rest changes are one of the
      prodromal clinical and behavioral expressions of the brain changes that underlie
      ARMS individuals.

PMID- 26220854
TI  - Can Heterosexist Music Cause Hiring Discrimination Against Sexual Minority Men?
      Testing the Effects of Prejudicial Media Messages.
AB  - Workplace heterosexism is a pervasive issue affecting lesbian, gay, bisexual, and
      transgender (LGBT) employees. This study investigated the influence of
      heterosexist media on hiring decisions by exposing 171 heterosexual undergraduate
      men to heterosexist rap music, nonheterosexist rap music, or no music and
      measuring their evaluations of a heterosexual and gay male professorial job
      applicant immediately afterward. As expected, participants exposed to the
      heterosexist music provided lower evaluations of the gay applicant than those
      exposed to no music, for two of the eight dimensions measured. Also, participants
      exposed to heterosexist messages were less willing to recommend and meet one-on
      one with a gay candidate than a heterosexual one. Music condition effects
      remained, even with demographic factors controlled. These findings suggest that
      media heterosexism may affect hiring decisions for GBT men and may also influence
      the treatment of these men in a workplace environment.

PMID- 26220855
TI  - A Chlamydia effector recruits CEP170 to reprogram host microtubule organization.
AB  - The obligate intracellular bacterial pathogen Chlamydia trachomatis deploys
      virulence effectors to subvert host cell functions enabling its replication
      within a specialized membrane-bound compartment termed an inclusion. The control
      of the host cytoskeleton is crucial for Chlamydia uptake, inclusion biogenesis
      and cell exit. Here, we demonstrate how a Chlamydia effector rearranges the
      microtubule (MT) network by initiating organization of the MTs at the inclusion
      surface. We identified an inclusion-localized effector that is sufficient to
      interfere with MT assembly, which we named inclusion protein acting on MTs
      (IPAM). We established that IPAM recruits and stimulates the centrosomal protein
      170 kDa (CEP170) to hijack the MT organizing functions of the host cell. We show
      that CEP170 is essential for chlamydial control of host MT assembly, and is
      required for inclusion morphogenesis and bacterial infectivity. Together, we
      demonstrate how a pathogen effector reprograms the host MT network to support its
      intracellular development. 

PMID- 26220857
TI  - Segmented TOF at 7 T MRI: Technique and clinical applications.
AB  - PURPOSE: Time-of-flight (TOF) MR angiography has an advantage of contrast and
      resolution in ultra-high field (7 T) MRI systems. However, increased specific
      absorption rate (SAR) prohibits the application of spatial saturation band,
      leading to venous contamination in maximum intensity projection (MIP) images.
      METHODS: A segmented k-space filling scheme with sparse venous saturation pulses
      was developed for 7 T TOF-MRA. The effectiveness of the segmented TOF sequence
      was verified by Bloch equation simulation and experiments on 3 T. The protocol on
      7 T was optimized and applied for healthy volunteers and patients with vascular
      diseases. RESULTS: Segmented TOF achieved equivalent contrast and venous
      suppression effect as conventional methods, while SAR values had a remarkable
      reduction and obeyed the limit of a 7 T MRI system. The decreased number of
      saturation pulses allowed shorter acquisition time than existing solutions. The
      comparison of segmented TOF and conventional TOF revealed flow direction in
      vascular diseases. CONCLUSION: Segmented TOF is proved to be a time-efficient way
      to achieve high-resolution angiograms without venous contamination at ultra-high
      field. The sequence holds strong promise for non-contrast clinical diagnosis on
      cerebrovascular diseases.

PMID- 26220858
TI  - Stejskal's formula for multiple-pulsed diffusion MRI.
AB  - A fundamental theoretical result for diffusion MRI is the formula by Stejskal
      showing that the diffusion NMR signal is proportional to the Fourier transform of
      the diffusion displacement probability density function. Here this result is
      extended to multiple-pulsed diffusion MRI (MP-dMRI) by using a higher dimensional
      q-space formalism to express the diffusion-weighted signal for a sequence with N
      diffusion wave vectors in terms of a Fourier transform of a diffusion
      displacement probability density function in a 3N-dimensional space. As an
      illustration of the application of this extended version of Stejskal's formula,
      it is used to analyze the cumulant expansion of the signal magnitude for MP-dMRI.

PMID- 26220856
TI  - Characterization of Cep85 - a new antagonist of Nek2A that is involved in the
      regulation of centrosome disjunction.
AB  - Nek2 has been implicated in centrosome disjunction at the onset of mitosis to
      promote bipolar spindle formation, and hyperactivation of Nek2 leads to the
      premature centrosome separation. Its activity, therefore, needs to be strictly
      regulated. In this study, we report that Cep85, an uncharacterized centrosomal
      protein, acts as a binding partner of Nek2A. It colocalizes with isoform A of
      Nek2 (Nek2A) at centrosomes and forms a granule meshwork enveloping the proximal
      ends of centrioles. Opposite to the effects of Nek2A, overexpression of Cep85 in
      conjunction with inhibition of the motor protein Eg5 (also known as KIF11) leads
      to the failure of centrosome disjunction. By contrast, depletion of Cep85 results
      in the precocious centrosome separation. We also define the Nek2A binding and
      centrosome localization domains within Cep85. Although the Nek2A-binding domain
      alone is sufficient to inhibit Nek2A kinase activity in vitro, both domains are
      indispensable for full suppression of centrosome disjunction in cells. Thus, we
      propose that Cep85 is a bona fide Nek2A-binding partner that surrounds the
      proximal ends of centrioles where it cooperates with PP1gamma (also known as
      PPP1CC) to antagonize Nek2A activity in order to maintain the centrosome
      integrity in interphase in mammalian cells. 

PMID- 26220859
TI  - Prostate diffusion imaging with distortion correction.
AB  - PURPOSE: Diffusion imaging in the prostate is susceptible to distortion from B0
      inhomogeneity. Distortion correction in prostate imaging is not routinely
      performed, resulting in diffusion images without accurate localization of tumors.
      We performed and evaluated distortion correction for diffusion imaging in the
      prostate. MATERIALS AND METHODS: 28 patients underwent pre-operative MRI (T2,
      Gadolinium perfusion, diffusion at b=800 s/mm(2)). The restriction spectrum
      protocol parameters included b-values of 0, 800, 1500, and 4000 s/mm(2) in 30
      directions for each nonzero b-value. To correct for distortion, forward and
      reverse trajectories were collected at b=0 s/mm(2). Distortion maps were
      generated to reflect the offset of the collected data versus the corrected data.
      Whole-mount histology was available for correlation. RESULTS: Across the 27
      patients evaluated (excluding one patient due to data collection error), the
      average root mean square distortion distance of the prostate was 3.1 mm (standard
      deviation, 2.2mm; and maximum distortion, 12 mm). CONCLUSION: Improved
      localization of prostate cancer by MRI will allow better surgical planning,
      targeted biopsies and image-guided treatment therapies. Distortion distances of
      up to 12 mm due to standard diffusion imaging may grossly misdirect treatment
      decisions. Distortion correction for diffusion imaging in the prostate improves
      tumor localization.

PMID- 26220860
TI  - Dixon-based fat-free MR-angiography compared to first pass and steady-state high
      resolution MR-angiography using a blood pool contrast agent.
AB  - INTRODUCTION: Compared to standard arterial-only first-pass MR-angiography
      (FPMRA), imaging during the equilibrium phase of a blood pool contrast agent
      (steady state) has been shown to provide higher image quality and better stenosis
      grading. Homogenous Dixon fat-suppression promises to increase contrast by
      suppression of fat adjacent to vessels. This study was performed to compare
      diagnostic image quality and vessel-to-background contrasts in equilibrium phase
      Dixon-based fat-free MRA (DFSMRA) of run-off vessels to FPMRA imaging and
      equilibrium phase T1-weighted non-fat-suppressed ultra-high resolution MRA
      (SSMRA). MATERIAL AND METHODS: In a prospective, intra-individual comparative
      study, 17 patients with known or suspected peripheral arterial occlusive disease
      (PAOD; 11 men, mean age 65.6+/-18.1 [23-89] years) received FPMRA, DFSMRA, and
      SSMRA at 1.5 Tesla using a clinical whole body MRI scanner. All sequences were
      performed within the same session applying a single dose of a blood pool contrast
      agent (gadofosveset trisodium) that was injected during acquisition of FPMRA. The
      diagnostic image quality of the run-off vessels was evaluated on a 3-point scale.
      Quantitative analysis consisted of contrast-ratio (CR) measurements of vascular
      lumen signals compared to signals of adjacent muscle and fat. RESULTS: The
      average image quality of vessel visualization was rated highest in SSMRA (mean
      1.34+/-0.41), followed by standard FPMRA (mean 1.15+/-0.33) and DFSMRA (mean
      0.99+/-0.61). Image quality was rated similarly high in the thighs and pelvic
      region, whereas small vessels in the lower legs and in the feet were best
      visualized by SSMRA. CR of vascular lumen compared to adjacent fatty tissue was
      2.7 times higher in DFSMRA compared to SSMRA, whereas CR of vascular lumen to
      muscle was 1.3 times higher in SSMRA. CONCLUSION: Vessel to fat contrast is
      strongly increased in DFSMRA compared to T1-weighted ultra-high resolution non
      fat suppressed SSMRA, whereas vessel to muscle contrast is decreased in DFSMRA.
      Given the current technical limitations of DFSMRA, possible benefits are
      outweighed by advantages of first-pass imaging regarding arterial selectivity as
      well as advantages of SSMRA with respect to spatial resolution.

PMID- 26220861
TI  - Diffusion-weighted imaging of prostate cancer: effect of b-value distribution on
      repeatability and cancer characterization.
AB  - PURPOSE: To evaluate the effect of b-value distribution on the repeatability and
      Gleason score (GS) prediction of prostate cancer (PCa). METHODS: Fifty PCa
      patients underwent two repeated 3T diffusion-weighted imaging (DWI) examinations
      using 12 b values in the range from 0 to 2000s/mm(2) and diffusion time of
      20.3ms. Mean signal intensities of regions of interest, placed in PCa using whole
      mount prostatectomy sections as the reference, were fitted using monoexponential,
      kurtosis, stretched exponential, and biexponential models. In total, 4083
      different b-value combinations consisting of 2 to 12 b values were evaluated.
      Repeatability was assessed by intraclass correlation coefficient, ICC(3,1), and
      coefficient of repeatability (CoR). Areas under receiver operating characteristic
      curve (AUCs) for PCa characterization were estimated while the correlation of the
      fitted values with GS groups (3+3, 3+4, >3+4) was evaluated by using the Spearman
      correlation coefficient (rho). RESULTS: The parameters of monoexponential,
      kurtosis, and stretched exponential models estimated using only 4-5, 5-7, 5-7 b
      values, respectively, had similar ICC(3,1), CoR, AUC, and rho values as the
      parameters estimated using all 12 b values. Optimized b-value distributions
      demonstrated improved ICC(3,1) and CoR values but failed to improve AUC and rho
      values. The parameters of biexponential model demonstrated the worst
      repeatability and diagnostic performance. CONCLUSION: B-value distribution
      influences mainly the repeatability of DWI-derived parameters rather than the
      diagnostic performance.

PMID- 26220862
TI  - Micromotors with asymmetric shape that efficiently convert light into work by
      thermocapillary effects.
AB  - The direct conversion of light into work allows the driving of micron-sized
      motors in a contactless, controllable and continuous way. Light-to-work
      conversion can involve either direct transfer of optical momentum or indirect
      opto-thermal effects. Both strategies have been implemented using different
      coupling mechanisms. However, the resulting efficiencies are always very low, and
      high power densities, generally obtained by focused laser beams, are required.
      Here we show that microfabricated gears, sitting on a liquid-air interface, can
      efficiently convert absorbed light into rotational motion through a
      thermocapillary effect. We demonstrate rotation rates up to 300 r.p.m. under wide
      field illumination with incoherent light. Our analysis shows that thermocapillary
      propulsion is one of the strongest mechanisms for light actuation at the micron-
      and nanoscale. 

PMID- 26220863
TI  - Towards pathway-centric cancer therapies via pharmacogenomic profiling analysis
      of ERK signalling pathway.
AB  - BACKGROUND: Genomic heterogeneity in human cancers complicates gene-centric
      personalized medicine. Malignant tumors often share a core group of pathways that
      are perturbed by diverse genetic mutations. Therefore, one possible solution to
      overcome the heterogeneity challenge is a shift from gene-centric to pathway
      centric therapies. Pathway-centric perspectives, which underscore the need to
      understand key pathways and their critical properties, could address the
      complexity of cancer heterogeneity better than gene-centric approaches to aid
      cancer drug discovery and therapy. METHODS: We used large-scale pharmacogenomic
      profiling data provided by the Cancer Genome Project of the Wellcome Trust Sanger
      Institute and the Cancer Cell Line Encyclopedia. In a systematic in silico
      investigation of ERK signalling pathway components and topological structures
      determines their influences on pathway activity and targeted therapies. Mann
      Whitney U test was used to identify gene alterations associated with drug
      sensitivity with p values and Benjamini-Hochberg correction for multiple
      hypotheses testing. RESULTS: The analysis demonstrated that genetic alterations
      were crucial to activation of effector pathway and subsequent tumorigenesis,
      however drug sensitivity suffered from both drug effector and non-effector
      pathways, which were determined by not only underlying genomic alterations, but
      also interplay and topological relationship of components in pathway, suggesting
      that the combinatorial targets of key nodes in perturbed pathways may yield
      better treatment outcome. Furthermore, we proposed a model to provide a more
      comprehensive insight and understanding of pathway-centric cancer therapies.
      CONCLUSIONS: Our study provides a holistic view of factors influencing drug
      sensitivity and sheds light on pathway-centric cancer therapies.

PMID- 26220866
TI  - The NO-modified HIV protease inhibitor as a valuable drug for hematological
      malignancies: Role of p70S6K.
AB  - Covalent attachment of NO to the first approved HIV protease inhibitor Saquinavir
      (Saq-NO) expands the therapeutic potential of the original drug. Apart from
      retained antiviral activity, the modified drug exerts strong antitumor effects
      and lower toxicity. In the present study, we have evaluated the sensitivity of
      different hematological malignancies to Saq-NO. Saq-NO efficiently diminished the
      viability of Jurkat, Raji, HL-60 and K562 cells. While Jurkat and Raji cells
      (established from pediatric patients) displayed abrogated proliferative
      potential, HL-60 and K652 cells (originated from adults) exposed to Saq-NO
      treatment underwent caspase dependent apoptosis. In addition, similar sensitivity
      to Saq-NO was observed in mononuclear blood cells obtained from pediatric
      patients with acute lymphoblastic leukemia (ALL) and adult patients with acute
      myeloid leukemia (AML). Western blot analysis indicated p70S6 kinase as a
      possible intracellular target of Saq-NO action. Moreover, the addition of a NO
      moiety to Lopinavir resulted in improved antitumor potential as compared to the
      parental compound, suggesting that NO-derived HIV protease inhibitors are a
      potential new source of anticancer drugs with unique mode of action. 

PMID- 26220865
TI  - Prior cytopenia predicts worse clinical outcome in acute myeloid leukemia.
AB  - The prognosis of acute myeloid leukemia (AML) is influenced by both disease
      intrinsic and patient-related factors. In particular, AML following
      myelodysplastic syndrome (MDS) (AML with myelodysplasia-related changes, AML-MRC)
      has a poor prognosis. We hypothesized that patients with cytopenias prior to AML,
      but no known prior MDS, may share biologic features with AML-MRC. We evaluated
      140 AML patients without prior MDS who had complete blood count (CBC) data
      available 6-36 months prior to their diagnosis. Cytopenia, defined as clinically
      unexplained thrombocytopenia or macrocytic anemia, was present in 29/140 (21%)
      patients. Compared to non-cytopenic patients, AML patients with prior cytopenia
      were older and more often met morphologic or cytogenetic criteria for AML-MRC.
      Prior cytopenia was associated with shorter survival in patients with
      intermediate-risk cytogenetics (median OS 4.2 versus 24.1 months, p<0.0001), but
      not in patients with adverse-risk cytogenetics (median OS 4.4 versus 6.0 months,
      p=0.57). Prior thrombocytopenia, but not macrocytic anemia, was significantly
      associated with shorter overall survival (p=0.01) independent of treatment
      approach, karyotype risk, and age on multivariable analysis. Our data suggest
      that AML patients with prior cytopenias have features similar to AML-MRC, and in
      particular support the use of prior unexplained thrombocytopenia as an
      independent marker of high-risk disease. 

PMID- 26220864
TI  - Inflammation in chronic obstructive pulmonary disease and its role in
      cardiovascular disease and lung cancer.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by lung
      inflammation that persists after smoking cessation. This inflammation is
      heterogeneous but the key inflammatory cell types involved are macrophages,
      neutrophils and T cells. Other lung cells may also produce inflammatory
      mediators, particularly the epithelial cells. The main inflammatory mediators
      include tumor necrosis factor alpha, interleukin-1, interleukin-6, reactive
      oxygen species and proteases. COPD is also associated with systemic inflammation
      and there is a markedly increased risk of cardiovascular disease (particularly
      coronary artery disease) and lung cancer in patients with COPD. There is strong
      associative evidence that the inflammatory cells/mediators in COPD are also
      relevant to the development of cardiovascular disease and lung cancer. There are
      a large number of potential inhibitors of inflammation in COPD that may well have
      beneficial effects for these comorbidities. This is a not well-understood area
      and there is a requirement for more definitive clinical and mechanistic studies
      to define the relationship between the inflammatory process of COPD and
      cardiovascular disease and lung cancer. 

PMID- 26220867
TI  - Dynamics of ceramide generation and metabolism in response to fenretinide-
      Diversity within and among leukemia.
AB  - Fenretinide, N-(4-hydroxyphenyl)retinamide, (4-HPR), a synthetic retinoid, owes
      its cancer-toxic effects in part to the generation of ceramide, a potent tumor
      suppressing sphingolipid. As such, 4-HPR has garnered considerable interest as a
      chemotherapeutic. Cancer cells, however, via various metabolic routes, inactivate
      ceramide, and this can limit 4-HPR efficacy. As relatively little is known
      regarding 4-HPR-induced ceramide management in acute myelogeneous leukemia (AML),
      we undertook the present study to evaluate the impact of 4-HPR on ceramide
      production, metabolism, and cytotoxicity. In KG-1, HL-60, and HL-60/VCR
      (multidrug resistant) human leukemia cells, 4-HPR induced 15-, 2-, and 20-fold
      increases in ceramide (measured using [3H]palmitic acid), respectively. By use of
      specific inhibitors we show that ceramide was produced by sphingomyelinase and de
      novo pathways in response to 4-HPR exposure. HL-60/VCR cells metabolized ceramide
      to glucosylceramide (GC). 4-HPR exposure (1.25-10 MUM) reduced viability in all
      cell lines, with approximate IC50's ranging from 1 to 8.0 MUM. Reactive oxygen
      species (ROS) were generated in response to 4-HPR treatment, and the concomitant
      cytotoxicity was reversed by addition of vitamin E. 4-HPR was not cytotoxic nor
      did it elicit ceramide formation in K562, a chronic myeloid leukemia cell line;
      however, K562 cells were sensitive to a cell-deliverable form of ceramide, C6
      ceramide. Treatment of Molt-3, an acute lymphoblastic leukemia cell line, with 4
      HPR revealed moderate ceramide production (5-fold over control), robust
      conversion of ceramide to GC and sphingomyelin, and resistance to 4-HPR and C6
      ceramide. In conclusion, this work demonstrates diversity within and among
      leukemia in 4-HPR sensitivity and ceramide generation and subsequent metabolism.
      As such, knowledge of these metabolic pathways can provide guidance for enhancing
      ceramide-driven effects of 4-HPR in treatment of leukemia.

PMID- 26220869
TI  - Which factors may determine the necessary and feasible type of effectiveness
      evidence? A mixed methods approach to develop an instrument to help coverage
      decision-makers.
AB  - OBJECTIVES: Reimbursement decisions require evidence of effectiveness and, in
      general, a blinded randomised controlled trial (RCT) is the preferred study
      design to provide it. However, there are situations where a cohort study, or even
      patient series, can be deemed acceptable. The aim of this study was to develop an
      instrument that first examines which study characteristics of a blinded RCT are
      necessary, and then, if particular characteristics are considered necessary,
      examines whether these characteristics are feasible. DESIGN: We retrospectively
      studied 22 interventions from 20 reimbursement reports concerning medical
      specialist care made by the Dutch National Health Care Institute (ZIN) to
      identify any factors that influenced the necessity and feasibility of blinded
      RCTs, and their constituent study characteristics, that is, blinding,
      randomisation and a control group. A literature review was performed to identify
      additional factors. Additional expertise was included by interviewing eight
      experts in epidemiology, medicine and ethics. The resulting instrument was called
      the FIT instrument (Feasible Information Trajectory), and was prospectively
      validated using three consecutive reimbursement reports. RESULTS: (Blinded) RCT
      evidence was lacking in 5 of 11 positive reimbursement decisions and 3 of 11
      negative decisions. In the reimbursement reports, we found no empirical evidence
      supporting situations where a blinded RCT is unnecessary. The literature also
      revealed few arguments against the necessity of a blinded RCT. In contrast, many
      factors influencing the feasibility of randomisation, a control group and
      blinding, were found in the reimbursement reports and the literature; for
      example, when a patient population is too small or when an intervention is common
      practice, randomisation will be hindered. CONCLUSIONS: Policy regarding the
      necessity and feasibility of different types of evidence of effectiveness would
      benefit from systematic guidance. The FIT instrument has the potential to support
      transparent, reproducible and well-founded decisions on appropriate evidence of
      effectiveness in medical specialist care.

PMID- 26220868
TI  - Validating prediction scales of type 2 diabetes mellitus in Spain: the SPREDIA-2
      population-based prospective cohort study protocol.
AB  - INTRODUCTION: The incidence of type 2 diabetes mellitus (T2DM) is increasing
      worldwide. When diagnosed, many patients already have organ damage or advance
      subclinical atherosclerosis. An early diagnosis could allow the implementation of
      lifestyle changes and treatment options aimed at delaying the progression of the
      disease and to avoid cardiovascular complications. Different scores for
      identifying undiagnosed diabetes have been reported, however, their performance
      in populations of southern Europe has not been sufficiently evaluated. The main
      objectives of our study are: to evaluate the screening performance and cut-off
      points of the main scores that identify the risk of undiagnosed T2DM and
      prediabetes in a Spanish population, and to develop and validate our own
      predictive models of undiagnosed T2DM (screening model), and future T2DM
      (prediction risk model) after 5-year follow-up. As a secondary objective, we will
      evaluate the atherosclerotic burden of the population with undiagnosed T2DM.
      METHODS AND ANALYSIS: Population-based prospective cohort study with baseline
      screening, to evaluate the performance of the FINDRISC, DANISH, DESIR, ARIC and
      QDScore, against the gold standard tests: Fasting plasma glucose, oral glucose
      tolerance and/or HbA1c. The sample size will include 1352 participants between
      the ages of 45 and 74 years. ANALYSIS: sensitivity, specificity, positive
      predictive value, negative predictive value, likelihood ratio positive,
      likelihood ratio negative and receiver operating characteristic curves and area
      under curve. Binary logistic regression for the first 700 individuals
      (derivation) and last 652 (validation) will be performed. All analyses will be
      calculated with their 95% CI; statistical significance will be p<0.05. ETHICS AND
      DISSEMINATION: The study protocol has been approved by the Research Ethics
      Committee of the Carlos III Hospital (Madrid). The score performance and
      predictive model will be presented in medical conferences, workshops, seminars
      and round table discussions. Furthermore, the predictive model will be published
      in a peer-reviewed medical journal to further increase the exposure of the
      scores.

PMID- 26220870
TI  - How well do health professionals interpret diagnostic information? A systematic
      review.
AB  - OBJECTIVE: To evaluate whether clinicians differ in how they evaluate and
      interpret diagnostic test information. DESIGN: Systematic review. DATA SOURCES:
      MEDLINE, EMBASE and PsycINFO from inception to September 2013; bibliographies of
      retrieved studies, experts and citation search of key included studies.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Primary studies that provided
      information on the accuracy of any diagnostic test (eg, sensitivity, specificity,
      likelihood ratios) to health professionals and that reported outcomes relating to
      their understanding of information on or implications of test accuracy. RESULTS:
      We included 24 studies. 6 assessed ability to define accuracy metrics: health
      professionals were less likely to identify the correct definition of likelihood
      ratios than of sensitivity and specificity. -25 studies assessed Bayesian
      reasoning. Most assessed the influence of a positive test result on the
      probability of disease: they generally found health professionals' estimation of
      post-test probability to be poor, with a tendency to overestimation. 3 studies
      found that approaches based on likelihood ratios resulted in more accurate
      estimates of post-test probability than approaches based on estimates of
      sensitivity and specificity alone, while 3 found less accurate estimates. 5
      studies found that presenting natural frequencies rather than probabilities
      improved post-test probability estimation and speed of calculations. CONCLUSIONS:
      Commonly used measures of test accuracy are poorly understood by health
      professionals. Reporting test accuracy using natural frequencies and visual aids
      may facilitate improved understanding and better estimation of the post-test
      probability of disease.

PMID- 26220871
TI  - Effectiveness and cost-effectiveness of telephone-based support versus usual care
      for treatment of pressure ulcers in people with spinal cord injury in low-income
      and middle-income countries: study protocol for a 12-week randomised controlled
      trial.
AB  - INTRODUCTION: Pressure ulcers are a common and severe complication of spinal cord
      injury, particularly in low-income and middle-income countries where people often
      need to manage pressure ulcers alone and at home. Telephone-based support may
      help people in these situations to manage their pressure ulcers. The aim of this
      study is to determine the effectiveness and cost-effectiveness of telephone-based
      support to help people with spinal cord injury manage pressure ulcers at home in
      India and Bangladesh. METHODS AND ANALYSIS: A multicentre (3 sites), prospective,
      assessor-blinded, parallel, randomised controlled trial will be undertaken. 120
      participants with pressure ulcers on the sacrum, ischial tuberosity or greater
      trochanter of the femur secondary to spinal cord injury will be randomly assigned
      to a Control or Intervention group. Participants in the Control group will
      receive usual community care. That is, they will manage their pressure ulcers on
      their own at home but will be free to access whatever healthcare support they
      can. Participants in the Intervention group will also manage their pressure
      ulcers at home and will also be free to access whatever healthcare support they
      can, but in addition they will receive weekly telephone-based support and advice
      for 12 weeks (15-25 min/week). The primary outcome is the size of the pressure
      ulcer at 12 weeks. 13 secondary outcomes will be measured reflecting other
      aspects of pressure ulcer resolution, depression, quality of life, participation
      and satisfaction with healthcare provision. An economic evaluation will be run in
      parallel and will include a cost-effectiveness and a cost-utility analysis.
      ETHICS AND DISSEMINATION: Ethical approval was obtained from the Institutional
      Ethics Committee at each site. The results of this study will be disseminated
      through publications and presented at national and international conferences.
      TRIAL REGISTRATION NUMBER: ACTRN12613001225707.

PMID- 26220872
TI  - Prediction and prognostication of neurological deterioration in patients with
      acute ICH: a hospital-based cohort study.
AB  - OBJECTIVE: Patients with intracerebral haemorrhage (ICH) are at high risk of
      neurological deterioration (ND). We aimed at establishing predictors of early ND
      (END) as well as late ND (LND) and at exploring the impact of neurological
      stability during the first week on long-term prognosis. DESIGN: We conducted this
      study as a retrospective cohort study. ND was evaluated based on the
      consciousness and severity of neurological symptoms. ND during the first 24 h
      after admission was defined as early ND and from 24 h to 7 days as LND. Patients
      were followed up until February 2015. PARTICIPANTS: We included 300 patients with
      acute ICH (<=4.5 h from symptom onset) who were admitted to our institution from
      March 2009 to January 2015. SETTING: Section of Acute Neurology, Department of
      Neurology, Bispebjerg Hospital is a specialised referral centre receiving
      patients with acute stroke from the entire capital region of Denmark. RESULTS: We
      found that a spot sign on CT angiography (OR 10.7 CI 4.79 to 24.3) and extensive
      degree of interventricular haemorrhage (IVH) (OR 8.73 CI 2.87 to 26.5) were
      independent predictors of END, whereas a degree of comorbidity (Charlton Index),
      admission stroke severity and degree of IVH predicted LND. On follow-up imaging,
      haematoma expansion was independently associated with END (OR 6.1 CI 2.2 to
      17.3), and expansion of IVH was independently associated with both END (OR 1.7 CI
      1.2 to 2.3 per point increase) and LND (OR 2.3 CI 1.3 to 4.2 per point increase).
      ND during the first week was associated with a 1-year mortality of 60.5%,
      compared with 9.2% among the patients who remained stable. CONCLUSIONS: These
      results suggest that stability during the first week entails an optimistic
      prognosis. A relatively easy and effective risk stratification of END and LND is
      possible on admission based on the spot sign, IVH and clinical parameters.

PMID- 26220873
TI  - A case-control study of post-traumatic endophthalmitis at a Spanish hospital.
AB  - Our aim was to identify the potential risk factors for developing post-traumatic
      endophthalmitis (PTE) and the possible measures of prevention. Retrospective case
      control study, with 15 cases of PTE and 2 matched controls. We reviewed the
      medical records of the cases and their respective controls during the period 1996
      2008 at a Spanish Hospital. We collected demographic data and information about
      the type of trauma, the potential risk factors, comorbidities, microbial
      isolations, antimicrobial susceptibility, administered treatments, and the visual
      outcome. The independent predictor factors identified for PTE were intraocular
      foreign body (IOFB) (OR 5.48; CI 95 % 1.05-28.7), dirty wound (OR 4.91; CI 95 %
      0.96-25.3), and wound closure delays of 24 h or more (OR 5.48; CI 95 % 1.05
      28.7). The probability of endophthalmitis in patients without these risk factors
      was 5.9 %, but ascended to 65.3 % and 90.3 %, in those patients with two and
      three risk factors, respectively. Infected patients presented a complication rate
      of 80 %, with an evisceration rate of 53 %; both were significantly associated
      with infection. The visual outcome was poor and related to the presence of IOFB
      and virulent microorganisms (Bacillus sp., filamentous fungus), visual acuity at
      presentation, and retinal detachment. Patients who presented an IOFB, dirty
      wound, and delayed wound closure were 15 times more likely to develop infection,
      and when infected, patients fared much worse than those non-infected. We thus
      recommend aggressive prophylactic measures in patients with these risk factors,
      adding antifungal prophylaxis when the injury is contaminated with vegetable
      matter. 

PMID- 26220874
TI  - Ubiquitous Graphene Electronics on Scotch Tape.
AB  - We report a novel concept of graphene transistors on Scotch tape for use in
      ubiquitous electronic systems. Unlike common plastic substrates such as polyimide
      and polyethylene terephthalate, the Scotch tape substrate is easily attached onto
      various objects such as banknotes, curved surfaces, and human skin, which implies
      potential applications wherein electronics can be placed in any desired position.
      Furthermore, the soft Scotch tape serves as an attractive substrate for
      flexible/foldable electronics that can be significantly bent, or even crumpled.
      We found that the adhesive layer of the tape with a relatively low shear modulus
      relaxes the strain when subjected to bending. The capacitance of the gate
      dielectric made of oxidized aluminum oxide was 1.5 MUF cm(-2), so that a supply
      voltage of only 2.5 V was sufficient to operate the devices. As-fabricated
      graphene transistors on Scotch tape exhibited high electron mobility of 1326 (+/
      155) cm(2) V(-1) s(-1); the transistors still showed high mobility of 1254 (+/
      478) cm(2) V(-1) s(-1) even after they were crumpled. 

PMID- 26220875
TI  - Using the phenoscape knowledgebase to relate genetic perturbations to phenotypic
      evolution.
AB  - The abundance of phenotypic diversity among species can enrich our knowledge of
      development and genetics beyond the limits of variation that can be observed in
      model organisms. The Phenoscape Knowledgebase (KB) is designed to enable
      exploration and discovery of phenotypic variation among species. Because
      phenotypes in the KB are annotated using standard ontologies, evolutionary
      phenotypes can be compared with phenotypes from genetic perturbations in model
      organisms. To illustrate the power of this approach, we review the use of the KB
      to find taxa showing evolutionary variation similar to that of a query gene.
      Matches are made between the full set of phenotypes described for a gene and an
      evolutionary profile, the latter of which is defined as the set of phenotypes
      that are variable among the daughters of any node on the taxonomic tree.
      Phenoscape's semantic similarity interface allows the user to assess the
      statistical significance of each match and flags matches that may only result
      from differences in annotation coverage between genetic and evolutionary studies.
      Tools such as this will help meet the challenge of relating the growing volume of
      genetic knowledge in model organisms to the diversity of phenotypes in nature.
      The Phenoscape KB is available at http://kb.phenoscape.org.

PMID- 26220876
TI  - Immunolocalization of large corneous beta-proteins in the green anole lizard
      (Anolis carolinensis) suggests that they form filaments that associate to the
      smaller beta-proteins in the beta-layer of the epidermis.
AB  - The distribution of large corneous beta-proteins of 18-43 kDa (Ac37, 39, and 40)
      in the epidermis of the lizard Anolis carolinensis is unknown. This study
      analyses the localization of these beta-proteins in different body scales during
      regeneration. Western blot analysis indicates most protein bands at 40-50 kDa
      suggesting they mix with alpha-keratin of intermediate filament keratin proteins.
      Ac37 is present in mature alpha-layers of most scales and in beta-cells of the
      outer scale surface in some scales but is absent in the Oberhautchen, in the
      setae and beta-layer of adhesive pads and in mesos cells. In differentiating beta
      keratinocytes Ac37 is present over 3-4 nm thick filaments located around the
      amorphous beta-packets and in alpha-cells, but is scarce in precorneous and
      corneous layers of the claw. Ac37 forms long filaments and, therefore, resembles
      alpha-keratins to which it probably associates. Ac39 is seen in the beta-layer of
      tail and digital scales, in beta-cells of regenerating scales but not in the
      Oberhautchen (and adhesive setae) or in beta- and alpha-layers of the other
      scales. Ac40 is present in the mature beta-layer of most scales and dewlap, in
      differentiating beta-cells of regenerating scales, but is absent in all the other
      epidermal layers. The large beta-proteins are accumulated among forming beta
      packets of beta-cells and are packed in the beta-corneous material of mature beta
      layer. Together alpha-keratins, large beta-proteins form the denser areas of
      mature beta-layer that may have a different consistence that the electron-paler
      areas.

PMID- 26220877
TI  - Posterior reversible leukoencephalopathy syndrome with spinal cord involvement in
      a 9-year-old girl.
AB  - We report the youngest pediatric case of posterior reversible leukoencephalopathy
      syndrome confined to brainstem and spinal cord. At presentation bicytopenia,
      renal derangement, visual disturbances, magnetic resonance imaging findings,
      increased protein content, IgG index and cell count in the cerebrospinal fluid
      led us to extensive search for myelitis. She received a short course of steroid
      treatment. The final diagnosis was hypertension due to reflux nephropathy. Severe
      hypertension that exceeds the range of autoregulation in anterior spinal
      territory may result in spinal posterior reversible leukoencephalopathy syndrome.
      Clinicians should be aware of spinal posterior reversible leukoencephalopathy
      syndrome when cases have extensive lesions in the brainstem and spinal cord with
      none or minimal clinical findings, so called "clinical radiologic dissociation". 

PMID- 26220878
TI  - Ramelteon as adjunctive therapy for delirium referred to a consultation-liaison
      psychiatry service: a retrospective analysis.

PMID- 26220879
TI  - Effects of mahjong on the cognitive function of middle-aged and older people.

PMID- 26220880
TI  - Is melanoma survival influenced by month of diagnosis?
AB  - BACKGROUND: Despite being a well-documented phenomenon, seasonal variation in the
      incidence of cutaneous melanoma is poorly understood, and data on the seasonality
      of melanoma survival are scarce. We sought to explore the seasonal variation in
      melanoma incidence and survival in Belgium and to assess the characteristics and
      outcomes of cases diagnosed during the seasonal peak. METHODS: All cases of
      invasive cutaneous melanoma-patients over 15 years of age and registered by the
      Belgian Cancer Registry (BCR) from 2004 to 2009-were included (n=9782). Monthly
      variations in incidence were estimated by the ratio of the number of cases
      diagnosed each month to that diagnosed in January (Rmonth/January) using Nam's
      method. The observed and relative 5-year survival rates were adjusted on patient
      and tumour characteristics using Cox proportional hazards regression models and
      generalised linear models with a Poisson error structure, respectively. RESULTS:
      A peak in melanoma incidence was observed in June (RJune/January=1.64, 95%
      confidence interval (CI)=1.54-1.73). The 5-year observed survival (OS) and
      relative survival (RS) rates were significantly higher for patients diagnosed in
      June compared with other months (OSJune=84%, 95%CI=81-86 versus
      OSOthermonths=79%, 95%CI=78-80; RSJune=93%, 95%CI=90-95 versus RSothermonths=87%,
      95%CI=86-88). After adjustment, the 5-year OS remained significantly higher for
      patients diagnosed in June (hazard ratioJune=0.78, 95%CI=0.62-0.98); however, the
      5-year RS was no longer significantly different for patients diagnosed in June
      compared with other months (relative excess riskJune=1.16, 95%CI=0.73-1.84).
      CONCLUSIONS: This study demonstrated a seasonal variation in melanoma incidence
      in Belgium with a peak in June for the period 2004-2009. When adjusted for
      patient and tumour characteristics, patients diagnosed in June had higher
      observed survival rates, but relative survival rates did not differ. Our findings
      do not support an influence of season of diagnosis on melanoma prognosis.

PMID- 26220881
TI  - Asymmetries in body condition and order of arrival influence competitive ability
      and survival in a coral reef fish.
AB  - Trade-offs between traits that influence an individual's competitive ability are
      important in determining community assembly and coexistence of individuals
      sharing the same resources. Populations of coral reef fish are structurally
      complex, so it is important to understand how these populations are shaped as a
      result of an individual's suite of traits and those of its competitors. We
      conducted a 2 * 2 factorial field experiment that manipulated body condition
      (high or low, manipulated through a feeding regime) and residency (resident or
      intruder, where the resident arrived at the habitat 3 h before the intruder) to
      evaluate effects on competitive ability and survival. Prior residency alleviated
      the disadvantage of a low body condition with respect to aggression, which was
      similar between low-condition residents and high-condition intruders. However,
      high-condition residents displayed a significantly greater level of aggression
      than intruders, regardless of whether intruders were from high- or low-condition
      treatments. For intruders to have a high probability of becoming dominant, they
      needed to have a large body condition advantage. Mortality trajectories suggested
      that body condition modified the effect of prior residency, and intruders were
      more likely to suffer mortality if they had a low body condition because
      residents pushed them away from shelter. Our results highlight that the negative
      effects of some traits may be compensated for by the positive effects of other
      traits, and that the specific ecological context an individual faces (such as the
      characteristics of its competitors) can have a major influence on successful
      establishment and persistence.

PMID- 26220882
TI  - How Important Is Having Amenities Within Walking Distance to Middle-Aged and
      Older Adults, and Does the Perceived Importance Relate to Walking?
AB  - OBJECTIVE: This study examined how important walking to amenities (e.g., food
      store, park) is to middle-aged and older adults and whether this relates to
      walking. The relationship between walking to amenities and overall activity level
      was also explored. METHOD: The study was based on interviews conducted with 778
      individuals aged 45 to 94 years. Overall activity level was measured objectively
      using pedometers. RESULTS: A large proportion of participants did not think it
      was very important to have amenities within walking distance, and the majority of
      participants drove to get there, even among individuals who reported it was very
      important to have the amenities within walking distance. Self-reported walking to
      certain amenities (e.g., park) was associated with overall activity. DISCUSSION:
      The study underscores the impact of a car culture where the tendency to drive is
      paramount. It suggests the need to promote the importance of walking as part of
      an active, healthy lifestyle.

PMID- 26220883
TI  - Effect of bone marrow-derived stem cells and bone morphogenetic protein-2 on
      treatment of osteoradionecrosis in a rat model.
AB  - PURPOSE: We investigated the effect of rat mesenchymal stem cells (rMSCs) and
      bone morphogenetic protein-2 (BMP-2) on the osseous healing of osteoradionecrosis
      in the rat mandible, depending on application time. MATERIAL AND METHODS: One
      week after irradiation (30 Gy) on the right mandible, all molar teeth were
      extracted. In Group 1 (n = 25), rMSCs and/or BMP-2 carried with hydrogel were
      applied immediately after surgery. In Group 2 (n = 25), application was done 4
      weeks after surgery, after the occurrence of osteoradionecrosis. No hydrogel (n =
      5), hydrogel alone (n = 5), hydrogel with 2 * 10(4) rMSCs (n = 5), hydrogel with
      10 MUg of BMP-2 (n = 5), or hydrogel with 10 MUg of BMP-2 and 2 * 10(4) rMSCs (n
      = 5) was applied. Micro-CT data of bone healing were collected at 4 weeks post
      application. RESULTS: In Group 1, BMP-2 was effective in increasing both bone
      volume (BV) and bone mineral density (BMD), whereas rMSCs were not. In Group 2,
      the combined application of rMSCs and BMP-2 significantly increased BMD and BV
      compared to values in the groups without hydrogel and with hydrogel alone.
      CONCLUSION: Osseous healing after post-irradiation trauma in rats was enhanced
      immediately after dentoalveolar trauma by application of BMP-2, whereas the
      combined application of rMSCs and BMP-2 was most effective after
      osteoradionecrosis occurred.

PMID- 26220884
TI  - Microsurgical reconstruction of the head and neck region: Current concepts of
      maxillofacial surgery units worldwide.
AB  - INTRODUCTION: Microvascular surgery following tumor resection has become an
      important field of oral maxillofacial surgery (OMFS). Following the surveys on
      current reconstructive practice in German-speaking countries and Europe, this
      paper presents the third phase of the project when the survey was conducted
      globally. METHODS: The DOESAK questionnaire has been developed via a multicenter
      approach with maxillofacial surgeons from 19 different hospitals in Germany,
      Austria and Switzerland. It was distributed in three different phases to a
      growing number of maxillofacial units in German-speaking clinics, over Europe and
      then worldwide. RESULTS: Thirty-eight units from Germany, Austria and
      Switzerland, 65 remaining European OMFS-departments and 226 units worldwide
      responded to the survey. There is wide agreement on the most commonly used flaps,
      intraoperative rapid sections and a trend towards primary bony reconstruction. No
      uniform concepts can be identified concerning osteosynthesis of bone transplants,
      microsurgical techniques, administration of supportive medication and
      postoperative monitoring protocols. Microsurgical reconstruction is the gold
      standard for the majority of oncologic cases in Europe, but worldwide, only every
      second unit has access to this technique. CONCLUSION: The DOESAK questionnaire
      has proven to be a valid and well accepted tool for gathering information about
      current practice in reconstructive OMFS surgery. The questionnaire has been able
      to demonstrate similarities, differences and global inequalities.

PMID- 26220885
TI  - Leukocyte-platelet-rich plasma diminishes bone matrix deposition in rat calvaria
      treated with autograft due to simultaneous increase in immunohistochemical
      expression of Indian Hedgehog, transforming growth factor-beta, and parathyroid-1
      receptor.
AB  - PURPOSE: This study evaluated the immunohistochemical presence of Indian Hedgehog
      (IHH), transforming growth factor-beta (TGF-beta), and parathyroid-1 receptor
      (PTH1R) in calvaria bone repair, and compared these results with the histological
      bone matrix features in defects treated with autograft in the presence or absence
      of L-PRP. MATERIAL AND METHODS: An artificial bone defect measuring 5 * 1 mm was
      produced in the calvaria of 28 Wistar rats. Randomly the defects were treated
      with autograft and autograft mixed with L-PRP. The animals were euthanized at 15
      and 40 days post-surgery. Data were analyzed by Student-Newman-Keuls test (p <=
      .05) for immunohistochemical interpretation. RESULTS: The results revealed that
      the histological characteristic of bone matrix deposited in the defect was
      different in the defects treated with L-PRP. The group that received only the
      autograft demonstrated larger haversian bone matrix deposited, whereas the group
      that received autograft mixed with L-PRP revealed trabecular bone deposition.
      These results coincided with significantly higher immunopositivity for IHH, TGF
      beta1, and PTH1R in the L-PRP group. CONCLUSION: These results suggest that L-PRP
      altered the biological characteristic of the autograft, increasing the bone cells
      IHH+ but inducing a trabecular bone associated with intense quantities of TGF
      beta and PTH1R.

PMID- 26220886
TI  - Erythrobacter atlanticus sp. nov., a bacterium from ocean sediment able to
      degrade polycyclic aromatic hydrocarbons.
AB  - A Gram-stain-negative, motile, rod-shaped, orange-pigmented bacterium able to
      degrade polycyclic aromatic hydrocarbons was isolated from deep-sea sediment of
      the Atlantic Ocean and subjected to a polyphasic taxonomic study. The strain,
      designated s21-N3T, could grow at 4-37  degrees C (optimum 28  degrees C), at pH
      5-10 (optimum pH 7-8) and with 1-7 % (w/v) NaCl (optimum 2-3 %). Strain s21-N3T
      was positive for nitrate reduction, denitrification, aesculin hydrolysis, oxidase
      and catalase, but negative for indole production and urease. Phylogenetic
      analyses based on 16S rRNA gene sequences showed that strain s21-N3T formed a
      distinct branch within the genus Erythrobacter, sharing high similarities with
      three closely related strains, Erythrobacter marinus HWDM-33T (98.67 %),
      'Erythrobacter luteus' KA37 (97.80 %) and Erythrobacter gangjinensis K7-2T (97.59
      %). The similarities between strain s21-N3T and other type strains of recognized
      species within the genus Erythrobacter ranged from 95.00 to 96.47 %. The digital
      DNA-DNA hybridization values and average nucleotide identity (ANI) values between
      strain s21-N3T and the three closely related strains Erythrobacter marinus HWDM
      33T, 'Erythrobacter luteus' KA37 and Erythrobacter gangjinensis K7-2T were 18.60,
      18.00 and 18.50 % and 74.24, 72.49 and 72.54 %, respectively. The principal fatty
      acids were summed feature 8 (C18 : 1omega7c/omega6c) and summed feature 3 (C16 :
      1omega7c/omega6c). The respiratory lipoquinone was identified as Q-10. The major
      polar lipids comprised sphingoglycolipid, phosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylcholine and diphosphatidylglycerol. The G+C
      content of the chromosomal DNA was determined to be 58.18 mol%. The combined
      genotypic and phenotypic distinctiveness demonstrated that strain s21-N3T
      represents a novel species of the genus Erythrobacter, for which the name
      Erythrobacter atlanticus sp. nov. is proposed, with the type strain s21-N3T ( =
      MCCC 1A00519T = KCTC 42697T).

PMID- 26220887
TI  - Health-Related Quality of Life, Gender, and Culture of Older People Users of
      Health Services in the Multicultural Landscape of the City of Ceuta (Spain): A
      Cross-Sectional Study.
AB  - INTRODUCTION: Perceptions of health-related quality of life (HRQOL) are
      influenced by sociodemographic variables and by cultural-religious concepts of
      health, disease, and old age, among others. PURPOSE: To assess the HRQOL of older
      people in a population with a long history of multiculturalism, the city of Ceuta
      (Spain), and to compare the results with Spanish reference values. METHOD: A
      total of 372 individuals (55.4% females) were interviewed using the Spanish
      version of the Short Form-36 questionnaire. The subjects' mean age was 70.9 (SD =
      5) years: 253 were Christians, 93 Muslims, and 26 Jews, representing the
      proportions in the overall population of these cultural-religious groups.
      RESULTS: HRQOL differs according to the cultural-religious affiliation, which
      specifically affects social and psychological dimensions. DISCUSSION AND
      CONCLUSIONS: All groups obtained lower social function scores than the reference
      values, especially the Muslim and Jewish groups. IMPLICATIONS FOR PRACTICE:
      Health care providers may consider integrating culturally sensitive interventions
      to improve HRQOL.

PMID- 26220888
TI  - Early diffuse slowing on electroencephalogram in pediatric traumatic brain
      injury: Impact on management and prognosis.
AB  - INTRODUCTION: We hypothesized that the finding of diffuse slowing on bedside EEG
      in children with moderate to severe traumatic brain injury (TBI) is associated
      with prolonged hospital stay and worse functional outcomes. METHODS: We reviewed
      the medical records of all patients admitted to a single level I pediatric trauma
      center with moderate or severe TBI from 1/10-12/12 (defined by GCS<10 on
      admission). EEG monitoring results, patient demographics, clinical
      characteristics, length of stay and postinjury outcomes were recorded. We
      compared outcomes between patients with and without diffuse slowing on EEG. Data
      are presented as mean+/-SEM; p<0.05 was considered statistically significant.
      RESULTS: 219 children with TBI were identified; 81 had a bedside EEG performed
      within 48 hours of admission. Diffuse slowing was present in 50 (mean age 5.7+0.7
      years) and absent in 31 (n=31, mean age 4.2+0.9 years). Patients with diffuse
      slowing had a significant increase in ventilator days, ICU LOS, need for
      rehabilitation, and rehabilitation length of stay. CONCLUSION: The presence of
      diffuse slowing on EEG in children with TBI is associated with prolonged patient
      recovery and poor functional outcomes. This finding should prompt early
      consideration for rehabilitation and the need for intensive therapy.

PMID- 26220889
TI  - Lung maturity in esophageal atresia: Experimental and clinical study.
AB  - INTRODUCTION: Esophageal atresia and tracheoesophageal fistula (EA-TEF) survivors
      suffer respiratory morbidity of unclear pathogenesis. Defective lung
      morphogenesis has been described in the rat model. This study examined fetal lung
      growth and maturity in rats and patients with EA-TEF. METHODS: Pregnant rats
      received either adriamycin or vehicle. Control and adriamycin-exposed lungs, with
      and without EA-TEF, were weighed and processed for RT-PCR, DNA quantification,
      immunofluorescence and immunoblot analysis of TTF1, VEGF, Sp-B, and alpha-sma.
      Twenty human lungs were also processed for immunofluorescence and Alcian-blue
      staining. RESULTS: Lungs from fetuses with EA-TEF (E21) showed decreased total
      DNA; FGF7 and TTF1 mRNA expressions were upregulated at E15 and E18,
      respectively. Protein expression and immunofluorescent distribution of maturity
      markers were similar. Lungs from stillborns with EA-TEF showed decreased
      epithelial expression of Sp-B and VEGF whereas those from newborns tended to have
      less Sp-B and more VEGF and mucous glands. DISCUSSION: The lungs of rats with EA
      TEF were hypoplastic but achieved near-normal maturity. Stillborns with EA-TEF
      exhibited an apparently disturbed differentiation of the airway epithelium.
      Newborns with EA-TEF demonstrated subtle differences in the expression of
      differentiation markers, and increased number of mucous glands that could
      influence postnatal respiratory adaptation and explain some respiratory symptoms
      of EA-TEF survivors.

PMID- 26220890
TI  - Jejunal diverticulosis found in a patient with long-standing pneumoperitoneum and
      pseudo-obstruction on imaging: a case report.
AB  - Small bowel diverticulosis is a rare finding within the general population and
      jejunal diverticulosis, specifically, is even rarer. Clinical manifestations can
      range from post-prandial pain, constipation and malabsorption to serious
      complications, such as gastro-intestinal hemorrhage, perforation and acute
      intestinal obstruction. Here we describe the case of an 81-year-old gentleman who
      presented with a three-year history of abdominal pain and weight loss. Despite
      unremarkable physical examination and laboratory tests, persistent
      pneumoperitoneum and dilated loops of small bowel were found on imaging. Having
      been given a diagnosis of small bowel bacterial overgrowth, the patient underwent
      capsule endoscopy study for further evaluation of his small bowel. The capsule
      did not reach the colon and the patient never noted passing the capsule in his
      stool so, six months post-procedure, a computed tomography (CT) scan seemed to
      reveal the retained capsule. Subsequent exploratory laparotomy revealed 200 cm of
      atonic, dilated jejunum with impressive diverticula along the anti-mesenteric
      border. This case report is an example of an unusual set of presenting signs and
      symptoms of jejunal diverticulosis, including persistent pneumoperitoneum, pseudo
      obstruction and small bowel bacterial overgrowth. A literature review has
      revealed that these signs have been present in other cases of jejunal
      diverticulosis, although the etiology and pathophysiology is not clearly
      understood.

PMID- 26220891
TI  - GeneMatcher: a matching tool for connecting investigators with an interest in the
      same gene.
AB  - Here, we describe an overview and update on GeneMatcher
      (http://www.genematcher.org), a freely accessible Web-based tool developed as
      part of the Baylor-Hopkins Center for Mendelian Genomics. We created GeneMatcher
      with the goal of identifying additional individuals with rare phenotypes who had
      variants in the same candidate disease gene. We also wanted to facilitate
      connections to basic scientists working on orthologous genes in model systems
      with the goal of connecting their work to human Mendelian phenotypes. Meeting
      these goals will enhance the identification of novel Mendelian genes. Launched in
      September, 2013, GeneMatcher now has 2,178 candidate genes from 486 submitters
      spread across 38 countries entered in the database (June 1, 2015). GeneMatcher is
      also part of the Matchmaker Exchange (http://matchmakerexchange.org/) with an
      Application Programing Interface enabling submitters to query other databases of
      genetic variants and phenotypes without having to create accounts and data
      entries in multiple systems. 

PMID- 26220892
TI  - Mechanotransduction in small intestinal submucosa scaffolds: fabrication
      parameters potentially modulate the shear-induced expression of PECAM-1 and eNOS.
AB  - In small intestinal submucosa (SIS) scaffolds for functional tissue engineering,
      the impact of scaffold fabrication parameters on cellular response and tissue
      regeneration may relate to the mechanotransductory properties of the final
      arrangement of collagen fibres. We previously proved that two fabrication
      parameters, (a) preservation (P) or removal (R) of a dense collagen layer present
      in SIS, and (b) SIS in a final dehydrated (D) or hydrated (H) state, have an
      effect on the micromechanical environment of SIS. In a continuation of our
      studies, we herein hypothesized that these fabrication parameters also modulate
      early mechanotransduction in cells populating the scaffold. Mechanotransduction
      was investigated by seeding human umbilical vein endothelial cells (HUVECs) on
      scaffolds, exposing them to pulsatile shear stress (12 +/- 4 dyne/cm2 ) for 1 h
      (n = 5) in a cone-and-plate shear system, and evaluating the expression of the
      mechanosensitive genes Pecam1 and Enos by immunofluorescence and qPCR. Expression
      of mechanosensitive genes was highest in PD grafts, followed by PH and RH grafts.
      The RD group had similar expression to that of unsheared control cells,
      suggesting that the RD combination potentially reduced mechanotransduction of
      shear to cells. We concluded that the two fabrication parameters studied, which
      modify SIS micromechanics, also potentially modulated the early shear-induced
      expression of mechanosensitive genes in seeded HUVECs. Our findings suggest that
      fabrication parameters influence the outcome of SIS as a therapeutic scaffold.
      Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26220893
TI  - Psychometric investigation of benefit finding among long-term cancer survivors
      using the Medical Expenditure Panel Survey.
AB  - PURPOSE: Benefit finding has been shown to be beneficial for people with cancer
      and may be an indication that one is coping adequately with the stress of cancer.
      This study evaluated the psychometric properties of a four-item benefit finding
      measure from the cancer survivorship supplement of the Medical Expenditure Panel
      Survey (MEPS). METHODS: Long-term survivors (5-10 years post-diagnosis) of
      breast, prostate, colorectal or lung cancer or melanoma (n = 594) completed the
      MEPS cancer supplement survey in 2013. Four items asked about benefit finding
      after the cancer: stronger person, coping better, positive changes and having
      healthier habits. Information on sociodemographics, disease and activity
      limitations after the cancer was also collected. We examined factor structure,
      reliability (Kuder-Richardson 20) and validity. RESULTS: The four benefit finding
      items did not appear to measure one factor. Three of the benefit finding items
      (stronger person, coping better, positive changes) were related to gender,
      receipt of chemotherapy and activity limitations but not cancer stage, time since
      diagnosis or income. Having healthier habits was unrelated to any
      sociodemographic or disease variable. CONCLUSIONS: Three of the items (stronger
      person, coping better, positive changes) appeared to have validity as they were
      related to variables that literature has shown are related to benefit finding.
      However, having healthier habits is likely measuring a separate but related
      construct. This short instrument may be used in future studies assessing benefit
      finding post cancer; however, the four items should be analyzed separately.

PMID- 26220894
TI  - CORR Insights: Latissimus Dorsi and Teres Major Transfer With Reverse Shoulder
      Arthroplasty Restores Active Motion and Reduces Pain for Posterosuperior Cuff
      Dysfunction.

PMID- 26220895
TI  - Is Embolization an Effective Treatment for Recurrent Hemorrhage After Hip or Knee
      Arthroplasty?
AB  - BACKGROUND: Spontaneous recurrent hemorrhage after arthroplasty of the hip or
      knee is a rare condition. In patients who do not have coagulopathy, the likeliest
      etiology for hemarthrosis is hypertrophic vascular synovium. Treatments include
      arthroscopic or open synovectomy, or angiography with embolization; however,
      because the condition is rare, seldom reported, and debilitating, small case
      series characterizing the efficacy of any approach are important to allow a
      collective experience with this condition to emerge. QUESTIONS/PURPOSES: We
      attempted to (1) determine whether angiography with embolization can prevent
      recurrent hemarthrosis after hip or knee arthroplasty in a small series of
      patients with or without coagulopathy, and (2) evaluate complications associated
      with this intervention. METHODS: Between 2005 and 2014, seven patients presented
      with spontaneous, recurrent hemarthroses. One patient had polycythemia vera and
      factor XIII deficiency as underlying illnesses. All patients were treated with
      selective transarterial embolization, and all had followup at a minimum of 12
      months (range, 12-102 months; median, 74 months). Other treatments during this
      time included hematoma removals and flap operations in one patient, and
      indications for transarterial embolization included recurrent hemarthrosis. The
      patients included six men and one woman with a median age of 72 years (range, 61
      78 years). Five patients underwent one or more reoperations before transarterial
      embolization. A diagnostic workup for coagulopathy was performed in all patients;
      one patient was identified to have polycythemia ruba vera and factor XIII
      deficiency, however the patient still was treated with transarterial embolization
      because it was perceived to be the least invasive of available options. No other
      patients had a diagnosis of coagulopathy. Angiography showed hypervascularity in
      all patients and a contrast agent showed extravasation in two. Selective
      transarterial embolization of branches of the internal iliac artery, common
      femoral artery, deep femoral artery, or the popliteal artery was performed with
      polyvinyl alcohol particles, microspheres, and/or coils. Patients were followed
      clinically during 12 to 102 months (median, 74 months) to determine whether the
      hemorrhages recurred. RESULTS: Technical success was achieved in all patients. No
      procedure-related complications were reported. On followup, recurrent hemorrhage
      was reported in one patient who had a diagnosis of coagulopathy before the
      procedure. He underwent three reinterventions and five reoperations. Three months
      after initial embolization, a flap procedure was performed. CONCLUSIONS: In a
      small series of patients with a minimum followup of 1 year, we found selective
      transarterial embolization to be effective in patients without underlying
      coagulopathy in preventing recurrences of spontaneous recurrent hematoma or
      hemarthrosis of the hip and the knee. This condition is rare, therefore
      comparative trials are unlikely to be done. Because transarterial embolization is
      relatively low risk and generally well tolerated, we consider it to be a
      reasonable approach for consideration with other options such as arthroscopic or
      open synovectomy and revision arthroplasty. LEVEL OF EVIDENCE: Level IV,
      therapeutic study.

PMID- 26220896
TI  - Reply to Letter to the Editor: Negative Pressure Wound Therapy in Grade IIIB
      Tibial Fractures: Fewer Infections and Fewer Flap Procedures?

PMID- 26220899
TI  - Corrigendum.

PMID- 26220897
TI  - Phylogenetic assignment of Mycobacterium tuberculosis Beijing clinical isolates
      in Japan by maximum a posteriori estimation.
AB  - Intra-species phylogeny of Mycobacterium tuberculosis has been regarded as a clue
      to estimate its potential risk to develop drug-resistance and various
      epidemiological tendencies. Genotypic characterization of variable number of
      tandem repeats (VNTR), a standard tool to ascertain transmission routes, has been
      improving as a public health effort, but determining phylogenetic information
      from those efforts alone is difficult. We present a platform based on maximum a
      posteriori (MAP) estimation to estimate phylogenetic information for M.
      tuberculosis clinical isolates from individual profiles of VNTR types. This study
      used 1245 M. tuberculosis clinical isolates obtained throughout Japan for
      construction of an MAP estimation formula. Two MAP estimation formulae,
      classification of Beijing family and other lineages, and classification of five
      Beijing sublineages (ST11/26, STK, ST3, and ST25/19 belonging to the ancient
      Beijing subfamily and modern Beijing subfamily), were created based on 24 loci
      VNTR (24Beijing-VNTR) profiles and phylogenetic information of the isolates.
      Recursive estimation based on the formulae showed high concordance with their
      authentic phylogeny by multi-locus sequence typing (MLST) of the isolates. The
      formulae might further support phylogenetic estimation of the Beijing lineage M.
      tuberculosis from the VNTR genotype with various geographic backgrounds. These
      results suggest that MAP estimation can function as a reliable probabilistic
      process to append phylogenetic information to VNTR genotypes of M. tuberculosis
      independently, which might improve the usage of genotyping data for control,
      understanding, prevention, and treatment of TB. 

PMID- 26220898
TI  - Nerve injury and neuropathic pain - A question of age.
AB  - The effects of peripheral nerve injury on somatosensory processing and pain are
      highly dependent upon the age at which the damage occurs. Adult nerve injury
      rapidly triggers neuropathic pain, but this is not so if the same nerve injury is
      performed in animals below postnatal day (P) 28, consistent with observations in
      paediatric patients. However, longitudinal studies show that pain
      hypersensitivity emerges later in life, when the animal reaches adolescence, an
      observation that could be of clinical importance. Here we discuss the evidence
      that the central consequences of nerve damage are critically determined by the
      status of neuroimmune regulation at different ages. In the first postnatal weeks,
      when spinal somatosensory circuits are undergoing synaptic reorganisation, the
      'default' neuroimmune response is skewed in an anti-inflammatory direction,
      suppressing the excitation of dorsal horn neurons and preventing the onset of
      neuropathic pain. As animals grow up and the central nervous system matures, the
      neuroimmune profile shifts in a pro-inflammatory direction, unmasking a 'latent'
      pain response to an earlier nerve injury. The data predicts that nerve injury in
      infancy and childhood could go unnoticed at the time, but emerge as clinically
      'unexplained' or 'functional' pain in adolescence. 

PMID- 26220900
TI  - Autism Spectrum Disorders: Translating human deficits into mouse behavior.
AB  - Autism Spectrum Disorders are a heterogeneous group of neurodevelopmental
      disorders, with rising incidence but little effective therapeutic intervention
      available. Currently two main clinical features are described to diagnose ASDs:
      impaired social interaction and communication, and repetitive behaviors. Much
      work has focused on understanding underlying causes of ASD by generating animal
      models of the disease, in the hope of discovering signaling pathways and cellular
      targets for drug intervention. Here we review how ASD behavioral phenotypes can
      be modeled in the mouse, the most common animal model currently in use in this
      field, and discuss examples of genetic mouse models of ASD with behavioral
      features that recapitulate various symptoms of ASD. 

PMID- 26220901
TI  - Plant alkaloids as drug leads for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative illness associated with dementia
      and is most prevalent among the elderly population. Current medications can only
      treat symptoms. Alkaloids are structurally diverse and have been an important
      source of therapeutics for various brain disorders. Two US Food and Drug
      Administration (FDA)-approved acetylcholinesterase inhibitors for AD, galantamine
      and rivastigmine, are in fact alkaloids. In addition, clinical trials of four
      other extensively studied alkaloids-huperzine A, caffeine, nicotine, and
      indomethacin-have been conducted but do not convincingly demonstrate their
      clinical efficacy for AD. Interestingly, rhynchophylline, a known neuroprotective
      alkaloid, was recently discovered by in silico screening as an inhibitor of
      EphA4, a novel target for AD. Here, we review the pathophysiological mechanisms
      underlying AD, current treatment strategies, and therapeutic potential of several
      selected plant alkaloids in AD, highlighting their various drug targets and the
      key supportive preclinical and clinical studies. Future research should include
      more rigorous clinical studies of the most promising alkaloids, the further
      development of recently discovered candidate alkaloids, and the continual search
      for new alkaloids for relevant drug targets. It remains promising that an
      alkaloid drug candidate could significantly affect the progression of AD in
      addition to providing symptomatic relief. 

PMID- 26220902
TI  - The cap-translation inhibitor 4EGI-1 induces mitochondrial dysfunction via
      regulation of mitochondrial dynamic proteins in human glioma U251 cells.
AB  - Translation initiation factors (eIFs) are over-activated in many human cancers
      and may contribute to their progression. The small molecule 4EGI-1, a potent
      inhibitor of translation initiation through disrupting eIF4E/eIF4G interaction,
      has been shown to exert anti-cancer effects in human cancer cells. The goal of
      the present study was to evaluate the anti-cancer effects of 4EGI-1 in human
      glioma U251 cells. We found that 4EGI-1 impaired the assembly of the eIF4F
      complex, and inhibited proliferation of U251 cells via inducing apoptosis. 4EGI-1
      treatment induced collapse of mitochondrial membrane potential (MMP) and
      production of intracellular reactive oxygen species (ROS), which were prevented
      by the ROS scavenger N-acetyl-cysteine (NAC). In addition, 4EGI-1 inhibited
      mitochondrial ATP synthesis via suppressing complex I activity, but had no
      effects on mitochondrial biogenesis. The results of fluorescence staining showed
      that 4EGI-1 indeed fragmented the mitochondrial network of U251 cells. We found a
      significant decrease in optic atrophy type 1 (Opa-1) and mitofusin 1 (Mfn-1)
      related to fusion proteins as well as an increase in fission protein dynamin
      related protein 1 (Drp-1). Furthermore, the anti-cancer effects of 4GI-1 were
      partially nullified by knock down of Drp-1 using siRNA. These data indicate that
      the use of inhibitors that directly target the translation initiation complex
      eIF4F could represent a potential novel approach for human glioma therapy. 

PMID- 26220903
TI  - 7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental
      disorders.
AB  - Neurodevelopmental disorders are a group of conditions that arises from
      impairments of the central nervous system during its development. The causes of
      the various disorders are heterogeneous and the symptoms likewise are
      multifarious. Most of these disorders currently have very little available
      treatment that is effective in combating the plethora of serious symptoms. Brain
      derived neurotrophic factor (BDNF) is a fundamental neurotrophin with vital
      functions during brain development. Pre-clinical studies have shown that
      increasing BDNF signalling may be a potent way to prevent, arrest or even reverse
      abnormal neurodevelopmental events arising from a variety of genetic or
      environmental causes. However, many difficulties make BDNF problematic to
      administer in an efficient manner. The recent discovery of a small BDNF-mimetic,
      the naturally occurring flavonoid 7,8-dihydroxyflavone (7,8-DHF), may provide an
      avenue to allow efficient and safe activation of the BDNF pathway in tackling the
      symptoms of neurodevelopmental disorders. Here, evidence will be provided to
      support the potential of 7,8-DHF as a novel treatment for several
      neurodevelopmental disorders where the BDNF signalling pathway is implicated in
      the pathophysiology and where benefits are therefore most likely to be derived
      from its implementation. 

PMID- 26220904
TI  - Carvacrol attenuates traumatic neuronal injury through store-operated Ca(2+)
      entry-independent regulation of intracellular Ca(2+) homeostasis.
AB  - Searching for effective pharmacological agents for traumatic brain injury (TBI)
      treatment has largely been unsuccessful. The transient receptor potential
      melastatin 7 (TRPM7), a TRP channel that is essential for embryonic development,
      has been shown to mediate ischemic neuronal injury in vivo and in vitro, but
      global deletion of TRPM7 in mice is lethal. Here, carvacrol was used to
      investigate the protective effect of TRPM7 inhibition in an in vitro traumatic
      neuronal injury model. Carvacrol (0.5 and 1 mM) reduced lactate dehydrogenase
      (LDH) release, apoptosis and caspase-3 activation after traumatic injury in
      cortical neurons. These neuroprotective effects were accompanied by alleviated
      cytoplasmic calcium levels as measured by calcium imaging. In contrast, the
      thapsigargin (TG) induced store-operated calcium entry (SOCE) and the expression
      of SOCE related proteins in neurons were not altered by carvacrol treatment. The
      involvement of TRPM7 sensitive calcium influx in our in vitro model was confirmed
      by the results that bradykinin induced calcium influx was prevented by carvacrol
      in neurons. Furthermore, carvacrol significantly inhibited the induction of
      neuronal nitric oxide synthase (nNOS) after traumatic injury, and treatment with
      carvacrol and the nNOS inhibitor NLPA together had no extra effect on calcium
      concentration and neuronal injury. Thus, inhibition of TRPM7 function by
      carvacrol protects against traumatic neuronal injury, and might be a potential
      drug development strategy for the treatment of TBI. 

PMID- 26220905
TI  - Molecular Characterization of TaFAR1 Involved in Primary Alcohol Biosynthesis of
      Cuticular Wax in Hexaploid Wheat.
AB  - Cuticular waxes are complex mixtures of very long chain (VLC) fatty acids and
      their derivatives in which primary alcohols are the most abundant components in
      the leaf surface of common wheat (Triticum aestivum L.). However, the genes
      involved in primary alcohol biosynthesis in wheat are still largely unknown. Here
      we identified, via a homology-based approach, the TaFAR1 gene belonging to the
      fatty acyl-CoA reductases (FARs) from wheat. Heterologous expression of TaFAR1 in
      yeast (Saccharomyces cerevisiae) and in the Arabidopsis (Arabidopsis thaliana)
      cer4-3 mutant afforded production of C22 primary alcohol and C22-C24 primary
      alcohols, respectively, and transgenic expression of TaFAR1 in tomato (Solanum
      lycopersicum) cv MicroTom leaves and fruits resulted in the accumulation of C26
      C30 primary alcohols and C30-C34 primary alcohols, respectively. The TaFAR1
      protein was localized to the endoplasmic reticulum (ER) in rice (Oryza sativa L.)
      leaf protoplasts. Moreover, the TaFAR1 expression pattern across various organs
      correlated with the levels of primary alcohols accumulating in corresponding
      waxes, and with the presence of platelet-shaped epicuticular wax crystals formed
      by primary alcohols. A nullisomic-tetrasomic wheat line lacking TaFAR1 had
      significantly reduced levels of primary alcohols in its leaf blade and anther
      wax. TaFAR1 was located on chromosome 4AL and appeared to be highly conserved,
      with only one haplotype among 32 wheat cultivars. Finally, TaFAR1 expression was
      induced by drought and cold stress in an ABA-dependent manner. Taken together,
      our results show that TaFAR1 is an active enzyme forming primary alcohols
      destined for the wheat cuticle. 

PMID- 26220906
TI  - Calpain-Mediated Positional Information Directs Cell Wall Orientation to Sustain
      Plant Stem Cell Activity, Growth and Development.
AB  - Eukaryotic development and stem cell control depend on the integration of cell
      positional sensing with cell cycle control and cell wall positioning, yet few
      factors that directly link these events are known. The DEFECTIVE KERNEL1 (DEK1)
      gene encoding the unique plant calpain protein is fundamental for development and
      growth, being essential to confer and maintain epidermal cell identity that
      allows development beyond the globular embryo stage. We show that DEK1 expression
      is highest in the actively dividing cells of seeds, meristems and vasculature. We
      further show that eliminating Arabidopsis DEK1 function leads to changes in
      developmental cues from the first zygotic division onward, altered microtubule
      patterns and misshapen cells, resulting in early embryo abortion. Expression of
      the embryonic marker genes WOX2, ATML1, PIN4, WUS and STM, related to axis
      organization, cell identity and meristem functions, is also altered in dek1
      embryos. By monitoring cell layer-specific DEK1 down-regulation, we show that L1-
      and 35S-induced down-regulation mainly affects stem cell functions, causing
      severe shoot apical meristem phenotypes. These results are consistent with a
      requirement for DEK1 to direct layer-specific cellular activities and set
      downstream developmental cues. Our data suggest that DEK1 may anchor cell wall
      positions and control cell division and differentiation, thereby balancing the
      plant's requirement to maintain totipotent stem cell reservoirs while
      simultaneously directing growth and organ formation. A role for DEK1 in
      regulating microtubule-orchestrated cell wall orientation during cell division
      can explain its effects on embryonic development, and suggests a more general
      function for calpains in microtubule organization in eukaryotic cells. 

PMID- 26220907
TI  - Ankle anticipatory postural adjustments during gait initiation in healthy and
      post-stroke subjects.
AB  - BACKGROUND: Anticipatory postural adjustments during gait initiation have an
      important role in postural stability but also in gait performance. However, these
      first phase mechanisms of gait initiation have received little attention,
      particularly in subcortical post-stroke subjects, where bilateral postural
      control pathways can be impaired. This study aims to evaluate ankle anticipatory
      postural adjustments during gait initiation in chronic post-stroke subjects with
      lesion in the territory of middle cerebral artery. METHODS: Eleven subjects with
      post-stroke hemiparesis with the ability to walk independently and twelve healthy
      controls participated in this study. Bilateral electromyographic activity of
      tibialis anterior, soleus and medial gastrocnemius was collected during gait
      initiation to assess the muscle onset timing, period of activation/deactivation
      and magnitude of muscle activity during postural phase of gait initiation. This
      phase was identified through centre of pressure signal. FINDINGS: Post-stroke
      group presented only half of the tibialis anterior relative magnitude observed in
      healthy subjects in contralesional limb (t=2.38, P=0.027) and decreased soleus
      deactivation period (contralesional limb, t=2.25, P=0.04; ipsilesional limb,
      t=3.67, P=0.003) as well its onset timing (contralesional limb, t=3.2. P=0.005;
      ipsilesional limb, t=2.88, P=0.033) in both limbs. A decreased centre of pressure
      displacement backward (t=3.45, P=0.002) and toward the first swing limb (t=3.29,
      P=0.004) was observed in post-stroke subjects. INTERPRETATION: These findings
      indicate that chronic post-stroke subjects with lesion at middle cerebral artery
      territory present dysfunction in ankle anticipatory postural adjustments in both
      limbs during gait initiation.

PMID- 26220908
TI  - Current and novel therapeutic molecules and targets in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of
      brain cells causes memory loss and cognitive decline, i.e., dementia. The disease
      starts with mild symptoms and gradually becomes severe. AD is one of the leading
      causes of mortality worldwide. Several different hallmarks of the disease have
      been reported such as deposits of beta-amyloid around neurons,
      hyperphosphorylated tau protein, oxidative stress, dyshomeostasis of bio-metals,
      low levels of acetylcholine, etc. AD is not simple to diagnose since there is no
      single diagnostic test for it. Pharmacotherapy for AD currently provides only
      symptomatic relief and mostly targets cognitive revival. Computational biology
      approaches have proved to be reliable tools for the selection of novel targets
      and therapeutic ligands. Molecular docking is a key tool in computer-assisted
      drug design and development. Docking has been utilized to perform virtual
      screening on large libraries of compounds, and propose structural hypotheses of
      how the ligands bind with the target with lead optimization. Another potential
      application of docking is optimization stages of the drug-discovery cycle. This
      review summarizes the known drug targets of AD, in vivo active agents against AD,
      state-of-the-art docking studies done in AD, and future prospects of the docking
      with particular emphasis on AD. 

PMID- 26220909
TI  - Development of global health education at Johns Hopkins University School of
      Medicine: a student-driven initiative.
AB  - Global health is increasingly present in the formal educational curricula of
      medical schools across North America. In 2008, students at Johns Hopkins
      University School of Medicine (JHUSOM) perceived a lack of structured global
      health education in the existing curriculum and began working with the
      administration to enhance global health learning opportunities, particularly in
      resource-poor settings. Key events in the development of global health education
      have included the introduction of a global health intersession mandatory for all
      first-year students; required pre-departure ethics training for students before
      all international electives; and the development of a clinical global health
      elective (Global Health Leadership Program, GHLP). The main challenges to
      improving global health education for medical students have included securing
      funding, obtaining institutional support, and developing an interprofessional
      program that benefits from the resources of the Schools of Medicine, Public
      Health, and Nursing. Strategies used included objectively demonstrating the need
      for and barriers to more structured global health experiences; obtaining guidance
      and modifying existing resources from other institutions and relevant educational
      websites; and harnessing institution-specific strengths including the large Johns
      Hopkins global research footprint and existing interprofessional collaborations
      across the three schools. The Johns Hopkins experience demonstrates that with a
      supportive administration, students can play an important and effective role in
      improving global health educational opportunities. The strategies we used may be
      informative for other students and educators looking to implement global health
      programs at their own institutions. 

PMID- 26220910
TI  - Enhanced production of alpha-amylase by Penicillium chrysogenum in liquid culture
      by modifying the process parameters.
AB  - In this paper, we have assessed the role of changing physicochemical parameters
      and substrate types on the production of alpha-amylase enzyme from Penicillium
      chrysogenum, with a view to determining the optimal conditions required for its
      maximum production. The findings of this research revealed that, at pH 6 using
      linseed oil cake as substratum, alpha-amylase enzyme production was maximum
      (550.0 U/mL), when the fungi was incubated for 6 days at 30  degrees C in 0.1 M
      acetate buffer. Further, reasonably good production of the alpha-amylase enzyme
      was also observed at pH 9 with all the experimented carbon sources as substrates.
      Moreover, statistical analysis, using analysis of variance (ANOVA) carried out to
      study the impact of different studied parameters on the alpha-amylase enzyme
      production revealed that incubation period of 6-18 days is highly significant (p
      = 0.01) factor in amylotic activity of the P. chrysogenum. Under the researched
      out optimal conditions, P. chrysogenum is an economically viable option for the
      industrial and biotechnological production of alpha-amylase enzyme.

PMID- 26220911
TI  - Apremilast: A Review in Psoriasis and Psoriatic Arthritis.
AB  - Apremilast (Otezla((r))) is an oral phosphodiesterase 4 inhibitor indicated for
      the twice-daily treatment of adults with psoriasis and psoriatic arthritis (PsA).
      Its use in these patient populations has been assessed in two phase III clinical
      trial programmes (ESTEEM and PALACE). At 16 weeks in the two ESTEEM trials,
      apremilast reduced the severity and extent of moderate to severe plaque
      psoriasis, including nail, scalp and palmoplantar manifestations, versus placebo
      in adults, with these benefits generally being sustained over 52 weeks of
      treatment. Similarly, in three PALACE trials (PALACE 1-3), apremilast improved
      the signs and symptoms of PsA relative to placebo at 16 weeks in adults with
      active disease despite treatment with conventional synthetic and/or biologic
      disease-modifying anti-rheumatic drugs. These PsA benefits were generally
      sustained for up to 104 weeks of treatment; skin involvement, enthesitis and
      dactylitis also improved with the drug. Apremilast was generally well tolerated,
      with the most common adverse events being diarrhoea and nausea in the first year
      of treatment (usually occurring in the first 2 weeks after the first dose and
      resolving within 4 weeks) and nasopharyngitis and upper respiratory tract
      infection with continued treatment. Although further longer-term and comparative
      efficacy and tolerability data would be beneficial, the current clinical data
      indicate that apremilast is an effective and well tolerated option for the
      management of psoriasis and PsA in adults.

PMID- 26220912
TI  - Nivolumab: A Review in Advanced Melanoma.
AB  - An improved understanding of cancer genetics and immune regulatory pathways,
      including those associated with evasion of immune surveillance by tumours, has
      culminated in the development of several targeted therapies. One such strategy
      that acts to negate evasion of immune surveillance by tumours is inhibition of
      the programmed cell death receptor-1 (PD-1) checkpoint pathway. Intravenous
      nivolumab (Opdivo((r))), a PD-1 checkpoint inhibitor, is approved or in pre
      registration in various countries for use in adult patients with advanced
      melanoma, with the recommended monotherapy dosage being a 60-min infusion of 3
      mg/kg once every 2 weeks. In well-designed multinational trials, as monotherapy
      or in combination with ipilimumab (a cytotoxic T-lymphocyte antigen 4 checkpoint
      inhibitor), nivolumab significantly improved clinical outcomes and had a
      manageable tolerability profile in adult patients with advanced melanoma with or
      without BRAF mutations. Nivolumab monotherapy was associated with a higher
      objective response rate (ORR) than chemotherapy in treatment-experienced patients
      and a higher ORR and prolonged progression-free survival (PFS) and overall
      survival than dacarbazine in treatment-naive patients. In combination with
      ipilimumab, nivolumab was associated with an improved ORR and prolonged PFS
      compared with ipilimumab monotherapy in treatment-naive patients. In addition,
      nivolumab monotherapy significantly prolonged PFS and improved ORRs compared with
      ipilimumab monotherapy. The optimal combination regimen for immune checkpoint
      inhibitors remains to be fully elucidated, with various combination regimens and
      different sequences of individual immunotherapies currently being investigated in
      ongoing clinical trials. Given the significant improvements in outcomes
      associated with nivolumab in clinical trials, nivolumab monotherapy or
      combination therapy is a valuable first-line or subsequent treatment option for
      adult patients with unresectable or metastatic melanoma, irrespective of BRAF
      mutation status.

PMID- 26220914
TI  - Identity and relatedness as mediators between child emotional abuse and adult
      couple adjustment in women.
AB  - The empirical literature indicates that childhood emotional abuse (CEA) produces
      long lasting impairments in interpersonal relatedness and identity, often
      referred to as self-capacities. CEA has also been shown to negatively impact
      couple functioning. This study examined the role of identity and interpersonal
      conflicts in mediating the relationship between CEA and women's report of couple
      adjustment among 184 French Canadian women from the general population. Path
      analysis revealed that CEA was related to poorer couple adjustment through its
      impact on dysfunctional self-capacities and the experience of greater conflicts
      in relationships. Findings highlight the importance of assessing CEA to better
      explain couple adjustment in women with relationship difficulties and provide
      potential intervention targets based on the self-capacities framework.

PMID- 26220913
TI  - Aflibercept: A Review in Metastatic Colorectal Cancer.
AB  - Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor
      for vascular endothelial growth factor (VEGF), a key regulator of angiogenesis.
      It binds to all isoforms of VEGF-A as well as VEGF-B and placental growth factor,
      and, thus, prevents them from binding to and activating their cognate receptors.
      In the USA and EU, intravenously administered aflibercept in combination with an
      infusion of leucovorin, fluorouracil and irinotecan (FOLFIRI) is approved for the
      treatment of patients with metastatic colorectal cancer that is resistant to or
      has progressed after treatment with an oxaliplatin-containing regimen. The
      efficacy of aflibercept in this indication was assessed in a multinational,
      pivotal phase 3 trial (VELOUR), in which the approved regimen of aflibercept 4
      mg/kg every 2 weeks plus FOLFIRI significantly prolonged median overall survival
      by 1.44 months compared with FOLFIRI alone (primary endpoint). The addition of
      aflibercept also significantly prolonged progression-free survival and
      significantly increased the objective response rate compared with FOLFIRI alone.
      Addition of aflibercept to FOLFIRI was associated with anti-VEGF-related adverse
      events and an increased incidence of FOLFIRI-related adverse events, but the
      tolerability of the combination was generally acceptable in this pre-treated
      population. The most common grade 3 or 4 adverse events with aflibercept plus
      FOLFIRI included neutropenia, diarrhoea and hypertension. In conclusion,
      aflibercept plus FOLFIRI is a useful treatment option for patients with
      metastatic colorectal cancer previously treated with an oxaliplatin-containing
      regimen, with or without bevacizumab.

PMID- 26220915
TI  - Comparison of contrast enhancement and diffusion-weighted magnetic resonance
      imaging in healthy and cancerous breast tissue.
AB  - OBJECTIVE: To measure background parenchymal enhancement (BPE) and compare with
      other contrast enhancement values and diffusion-weighted MRI parameters in
      healthy and cancerous breast tissue at the clinical level. MATERIALS AND METHODS:
      This HIPAA-compliant, IRB approved retrospective study enrolled 77 patients (38
      patients with breast cancer - mean age 51.8 +/- 10.0 years; 39 high-risk patients
      for screening evaluation - mean age 46.3 +/- 11.7 years), who underwent contrast
      enhanced 3T breast MRI. Contrast enhanced MRI and diffusion-weighted imaging were
      performed to quantify BPE, lesion contrast enhancement, and apparent diffusion
      coefficient (ADC) metrics in fibroglandular tissue (FGT) and lesions. RESULTS:
      BPE did not correlate with ADC values. Mean BPE for the lesion-bearing patients
      was higher (43.9%) compared to that of the high-risk screening patients (28.3%,
      p=0.004). Significant correlation (r=0.37, p<0.05) was found between BPE and
      lesion contrast enhancement. CONCLUSION: No significant association was observed
      between parenchymal or lesion enhancement with conventional apparent diffusion
      metrics, suggesting that proliferative processes are not co-regulated in
      cancerous and parenchymal tissue.

PMID- 26220916
TI  - Can imaging criteria distinguish enchondroma from grade 1 chondrosarcoma?
AB  - PURPOSE: To minimize systematic bias and optimize agreement on imaging criteria
      in order to better define the accuracy of imaging criteria in the diagnosis of
      grade 1 chondrosarcoma. MATERIALS AND METHODS: Study was IRB-approved and HIPAA
      compliant; informed consent was waived. Records were reviewed and disclosed 53
      cases (38 women, 15 men ages 21-76) which were diagnosed as enchondroma or grade
      1 chondrosarcoma and had available radiographs, contrast-enhanced MRI, and
      definitive diagnosis by histology or 5-year follow-up. 2 MSK radiologists read
      the studies independently after a session where they agreed on criteria for
      malignancy. Interobserver variability was determined as raw variability and with
      the kappa statistic. Accuracy was determined compared to final diagnosis.
      Reliability of imaging features of chondrosarcoma was determined using regression
      analysis. RESULTS: The correct diagnosis of enchondroma was made on radiographs
      in 43 (67.2%) of readings, and on MRI in 37/64 (57.8%). The correct diagnosis of
      chondrosarcoma was made on radiographs in 5/24 (20.8%) of readings, and on MRI in
      14/24 (57.8%). A diagnosis of borderline lesion was made in 19/64 (29.7%) of
      enchondromas on radiographs and 18/64 (28.1%) on MRI. The false positive rate of
      radiographs for chondrosarcoma was 2/64 (3.1%) and the false positive rate of MRI
      was 9/64 (14.1%). There was substantial interobserver variability. Cortical
      thickening and bone expansion were rare but specific signs of chondrosarcoma.
      CONCLUSIONS: Both radiographs and MRI have limitations in the evaluation of low
      grade cartilage lesions. MRI has an increased rate of both true-positive and
      false-positive diagnosis compared to radiographs. Differences in the findings of
      this study compared to previous literature may reflect the influence of
      systematic biases.

PMID- 26220917
TI  - Dual-energy CT of the pancreas: improved carcinoma-to-pancreas contrast with a
      noise-optimized monoenergetic reconstruction algorithm.
AB  - PURPOSE: To evaluate a novel monoenergetic reconstruction algorithm (nMERA) with
      improved noise reduction for dual-energy CT (DECT) of pancreatic adenocarcinoma.
      MATERIALS AND METHODS: Sixty patients with suspected pancreatic carcinoma
      underwent dual-source dual-energy CT with arterial phase. Images were
      reconstructed as linearly-blended 120-kV series (M_0.6) and with the standard
      monoenergetic (sMERA) and the novel monoenergetic algorithm (nMERA) with photon
      energies of 40, 55, 70 and 80 keV. Objective image quality was compared regarding
      image noise, pancreas attenuation, signal-to-noise ratio (SNR) and pancreas-to
      lesion contrast. Subjective image quality was assessed by two observers. RESULTS:
      Thirty pancreatic adenocarcinomas were detected. nMERA showed significantly
      reduced image noise at low keV levels compared with sMERA images (55 keV: 7.19 +/
      2.75 vs. 20.68 +/- 7.01 HU; 40 keV: 7.33 +/- 3.20 vs. 37.22 +/- 14.66 HU) and
      M_0.6 (10.69 +/- 3.57 HU). nMERA pancreatic SNR was significantly superior to
      standard monoenergetic at 40 (47.02 +/- 23.41 vs. 9.37 +/- 5.83) and 55 keV
      (28.29 +/- 16.86 vs. 9.88 +/- 7.01), and M_0.6 series (11.42 +/- 6.00). Pancreas
      to-lesion contrast peaked in the nMERA 40 keV series (26.39 +/- 16.83) and was
      significantly higher than in all other series (p<0.001). nMERA 55 keV images
      series were consistently preferred by both observers over all other series
      (p<0.01). CONCLUSIONS: nMERA DECT can significantly improve image quality and
      pancreas-to-lesion contrast in the diagnosis of pancreatic adenocarcinoma.

PMID- 26220918
TI  - Immunogenicity assessment of monoclonal antibody products: A simulated case study
      correlating antibody induction with clinical outcomes.
AB  - Monoclonal antibodies are large molecules with complex structure and functions.
      They have a wide application for treatment of a broad range of chronic diseases
      and represent the largest class of biotherapeutic products. Given that
      biotherapeutic products may induce unwanted humoral and/or cellular immune
      responses in recipients, it is essential to investigate the immunogenicity of a
      product prior to licensure. The immune response is influenced by many factors and
      data generated in the pre-licensure studies are usually somewhat difficult for
      regulatory review. The knowledge and expertise required for this requires a
      thorough understanding of animal and human immunology as well as specific product
      characteristics, including mechanism of action, antibody assays and assessment of
      results in a given clinical context. The appropriate interpretation of
      immunogenicity data is of critical importance for defining the safety profile of
      a monoclonal antibody. Two case studies described in this paper were prepared to
      mimic a real situation in which regulators need to evaluate immunogenicity
      studies conducted by manufacturers of monoclonal antibody products. The specific
      objective of the case studies was to illustrate assessment of unwanted
      immunogenicity and the important factors that need to be considered in this
      context. Regulators and manufacturers who attended the World Health Organization
      (WHO) implementation workshop on Evaluation of Biotherapeutic Products, held in
      Seoul, Republic of Korea, in May 2014, participated in the case studies and
      provided valuable input. This article outlines the main aspects of immunogenicity
      discussed in these case studies and a summary of the lessons learned at this
      occasion. 

PMID- 26220919
TI  - [Drugs Effect on Cognition in the Elderly].
AB  - Many drugs can affect cognitive function in the elderly. Anticholinergic and
      psychotropic drugs can cause or exacerbate cognitive impairment and can increase
      the occurrence of dementia in the elderly. In healthy elderly adults,
      antihypertensive drugs could improve cognition and reduce the dementia risk. By
      contrast, randomized clinical trials evaluating the effect of statins and
      nonsteroidal anti-inflammatory drugs have not shown significant cognitive effect.

PMID- 26220920
TI  - [Tinnitus in a Patient Treated by Bleomycin for Kaposi's Sarcoma].
AB  - We describe a case of tinnitus occurred during a bleomycin monotherapy for
      Kaposi's sarcoma. 

PMID- 26220921
TI  - [Therapeutic Drug Monitoring of Olanzapine].
AB  - Olanzapine, atypical antipsychotic, is used to treat schizophrenia and bipolar
      disorder. Its therapeutic drug monitoring (TDM) is quite commonly done.
      Olanzapine is well absorbed orally (bioavailability 85%), with peak plasma
      occurring between 4 and 6 hours after oral administration. It is extensively
      metabolized by different hepatic enzymes (including CYP1A2 and CYP2D6 isoforms)
      to a large number of inactive metabolites, and its half-life is between 30 and 60
      hours. No specific therapeutic range, or threshold concentration could not be a
      consensus, but the higher intra-and interindividual variability, as well as the
      existence of studies suggesting a correlation between circulating concentrations
      of olanzapine and occurrence of therapeutic relapse or toxic phenomena appear to
      justify the STP for this molecule. Given these data, the interest of the STP was
      evaluated for this molecule to: recommended with therapeutic window of 20 ug/L to
      80 ug/L.

PMID- 26220922
TI  - [Therapeutic Drug Monitoring of Clozapine].
AB  - Clozapine is a prototypical atypical antipsychotic used to treat severe
      schizophrenia and for which a therapeutic drug monitoring (TDM) is quite commonly
      proposed. Clozapine is rapidly absorbed (maximum concentration reached within 1
      to 4 hours), and is extensively metabolized in the liver by CYP1A2 to an active
      metabolite (and to a lesser extent, to inactive metabolites via other enzymes).
      Its half-life is 8 to 16 h. A therapeutic range has been proposed for clozapine
      as some studies have reported both a relationship between low plasmatic
      concentrations and resistance to treatment (threshold level is likely between 250
      and 400 ug/L), and a relationship between high plasmatic concentrations and an
      increase in the occurrence of toxicity (alert level=1 000ug/L). Given the data
      obtained in different studies, the TDM was evaluated for this molecule, to:
      recommended.

PMID- 26220923
TI  - Curcumin Resource Database.
AB  - Curcumin is one of the most intensively studied diarylheptanoid, Curcuma longa
      being its principal producer. This apart, a class of promising curcumin analogs
      has been generated in laboratories, aptly named as Curcuminoids which are showing
      huge potential in the fields of medicine, food technology, etc. The lack of a
      universal source of data on curcumin as well as curcuminoids has been felt by the
      curcumin research community for long. Hence, in an attempt to address this
      stumbling block, we have developed Curcumin Resource Database (CRDB) that aims to
      perform as a gateway-cum-repository to access all relevant data and related
      information on curcumin and its analogs. Currently, this database encompasses
      1186 curcumin analogs, 195 molecular targets, 9075 peer reviewed publications,
      489 patents and 176 varieties of C. longa obtained by extensive data mining and
      careful curation from numerous sources. Each data entry is identified by a unique
      CRDB ID (identifier). Furnished with a user-friendly web interface and in-built
      search engine, CRDB provides well-curated and cross-referenced information that
      are hyperlinked with external sources. CRDB is expected to be highly useful to
      the researchers working on structure as well as ligand-based molecular design of
      curcumin analogs.

PMID- 26220924
TI  - Diagnostic outcomes following childhood non-specific abdominal pain: a record
      linkage study.
AB  - AIMS: Non-specific abdominal pain (NSAP) is the most common diagnosis on
      discharge following admission for abdominal pain in childhood. Our aim was to
      determine the risk of subsequent hospital diagnosis of organic and functional
      gastroenterological conditions following a diagnosis of NSAP, and to assess the
      persistence of this risk. METHODS: An NSAP cohort of 268,623 children aged 0-16
      years was constructed from linked English Hospital Episode Statistics from 1999
      to 2011. The control cohort (1,684,923 children, 0-16 years old) comprised
      children hospitalised with unrelated conditions. Clinically relevant outcomes
      were selected and standardised rate ratios were calculated. RESULTS: From the
      NSAP cohort, 15,515 (5.8%) were later hospitalised with bowel pathology and
      13,301 (5%) with a specific functional disorder. Notably, there was a 4.84 (95%
      CI 4.45 to 5.27) times greater risk of Crohn's disease following NSAP and a 4.23
      (4.13 to 4.33) greater risk of acute appendicitis than in the control cohort. The
      risk of irritable bowel syndrome (IBS) was 7.22 (6.65 to 7.85) times greater
      following NSAP. The risks of inflammatory bowel disease (IBD), IBS and functional
      disorder (unspecified) were significantly increased in all age groups except <2
      year-olds. The risk of underlying bowel pathology remained raised up to 10 years
      after first diagnosis with NSAP. CONCLUSIONS: Only a small proportion of those
      with NSAP go on to be hospitalised with underlying bowel pathology. However,
      their risk is increased even at 10 years after the first hospital admission with
      NSAP. Diagnostic strategies need to be assessed and refined and active
      surveillance employed for children with NSAP.

PMID- 26220925
TI  - RNA-Seq analysis of high NaCl-induced gene expression.
AB  - High extracellular NaCl is known to change expression of numerous genes, many of
      which are regulated by the osmoprotective transcription factor nuclear factor of
      activated T cells-5 (NFAT5). In the present study we employed RNA-Seq to provide
      a comprehensive, unbiased account of genes regulated by high NaCl in mouse
      embryonic fibroblast cells (MEFs). To identify genes regulated by NFAT5 we
      compared wild-type MEFs (WT-MEFs) to MEFs in which mutation of the NFAT5 gene
      inhibits its transcriptional activity (Null-MEFs). In WT-MEFs adding NaCl to
      raise osmolality from 300 to 500 mosmol/kg for 24 h increases expression of 167
      genes and reduces expression of 412. Raising osmolality through multiple passages
      (adapted cells) increases expression of 196 genes and reduces expression of 528.
      In Null-MEFs, after 24 h of high NaCl, expression of 217 genes increase and 428
      decrease, while in adapted Null-MEFs 143 increase and 622 decrease. Fewer than
      10% of genes are regulated in common between WT- and null-MEFs, indicating a
      profound difference in regulation of high-NaCl induced genes induced by NFAT5
      compared with those induced in the absence of NFAT5. Based on our findings we
      suggest a mechanism for this phenomenon, which had previously been unexplained.
      The NFAT5 DNA-binding motif (osmotic response element) is overrepresented in the
      vicinity of genes that NFAT5 upregulates, but not genes that it downregulates. We
      used Gene Ontology and manual curation to determine the function of the genes
      targeted by NFAT5, revealing many novel consequences of NFAT5 transcriptional
      activity. 

PMID- 26220926
TI  - Behcet's disease without oral ulcers presenting with erythema nodosum and deep
      venous thrombosis.
AB  - We present a young male with recurrent erythema nodosum and recent deep vein
      thrombosis with scrotal ulcers but no oral ulcers. He was diagnosed as having
      Behcet's disease (BD) and subsequently responded to immunosuppressants and
      anticoagulation. This case highlights that up to 2% patients with BD may not have
      oral ulcers. Timely institution of therapy in our patient resulted in a favorable
      outcome. 

PMID- 26220927
TI  - Subsequent pancreatitis and haemothorax in a patient of expanded dengue syndrome.
AB  - We report a case of expanded dengue syndrome, where two different presentations
      occurred subsequently. A patient of dengue haemorrhagic fever initially was
      admitted with acute pancreatitis, complicated with left pancreatic effusion, but
      later on, during resolution of pancreatitis and effusion, developed spontaneous
      right haemothorax. Such presentations, besides being rare themselves, have not
      been reported to occur subsequently, in the same patient, during the same disease
      process. 

PMID- 26220928
TI  - Reply to H.G. Muntz et al.

PMID- 26220929
TI  - In Response to "State of Cancer Care in America, 2015".

PMID- 26220930
TI  - Reducing Time to Antibiotic Administration for Febrile Neutropenia in the
      Emergency Department.
AB  - PURPOSE: Febrile neutropenia (FN) is an oncologic emergency, and prolonged time
      to antibiotic administration (TTA) is associated with increased hospital length
      of stay (LOS) and worse outcomes. We hypothesized that a febrile neutropenia
      pathway (FNP) quality initiative project would reduce TTA delays for febrile
      patients with cancer presenting to the emergency department (ED). METHODS: This
      prospective study compared ED FNP patients (> 18 years old), between June 2012
      and June 2013 with both historical and direct admissions (DA) cohorts at a
      multispecialty academic center. Interventions included providing patients with FN
      Alert cards, standardizing the definition of FN and recognizing it as a distinct
      chief complaint, revising ED triage level for FN, creating electronic FN order
      sets, administering empiric antibiotics before neutrophil count result, and
      relocating FN antibiotics to the ED. The primary outcome was TTA, with a target
      goal of 90 minutes after ED presentation. RESULTS: In total, 276 FN episodes in
      223 FNP patients occurred over the 12-month study period and were compared with
      107 episodes in 87 patients and 114 episodes in 101 patients in the historical
      and DA cohorts, respectively. Use of the FNP reduced TTA from 235 and 169 minutes
      in historical and DA cohorts, respectively, to 81 minutes, and from 96 to 68
      minutes when the order set was not used versus used in the FNP group (P < .001
      for all comparisons). Decrease in hospital LOS was not statistically significant.
      CONCLUSION: The ED FNP is a significant quality initiative with sustainable
      interventions, and was able to demonstrate value by decreasing TTA compared to
      both historical and DA controls in cancer patients presenting to the ED.

PMID- 26220931
TI  - Community Oncology Medical Homes: Physician-Driven Change to Improve Patient Care
      and Reduce Costs.
AB  - Although the patient-centered medical home is a well-established model of care
      for primary care providers, adoption by specialty providers has been relatively
      limited. Recently, there has been particular interest in developing specialty
      medical homes in medical oncology because of practice variation, care
      fragmentation, and high overall costs of care. In 2012, the Center for Medicare
      and Medicaid Innovation awarded Innovative Oncology Business Solutions a 3-year
      grant for their Community Oncology Medical Home (COME HOME) program to implement
      specialty medical homes in seven oncology practices across the country. We report
      our early experience and lessons learned.Through September 30, 2014, COME HOME
      has touched 16,353 unique patients through triage encounters, patient education
      visits, or application of clinical pathways. We describe the COME HOME model and
      implementation timeline, profile use of key services, and report patient
      satisfaction. Using feedback from practice sites, we highlight patient-centered
      innovations and overall lessons learned.COME HOME incorporates best practices
      care driven by triage and clinical pathways, team-based care, active disease
      management, enhanced access and care, as well as financial support for the
      medical home infrastructure. Information technology plays a central role,
      supporting both delivery of care and performance monitoring. Volume of service
      use has grown steadily over time, leveling out in second quarter 2014. The
      program currently averages 1,265 triage encounters, 440 extended hours visits,
      and 655 patient education encounters per month.COME HOME offers a patient
      centered model of care to improve quality and continuity of care. 

PMID- 26220932
TI  - A literature mining-based approach for identification of cellular pathways
      associated with chemoresistance in cancer.
AB  - Chemoresistance is a major obstacle to the successful treatment of many human
      cancer types. Increasing evidence has revealed that chemoresistance involves many
      genes and multiple complex biological mechanisms including cancer stem cells,
      drug efflux mechanism, autophagy and epithelial-mesenchymal transition. Many
      studies have been conducted to investigate the possible molecular mechanisms of
      chemoresistance. However, understanding of the biological mechanisms in
      chemoresistance still remains limited. We surveyed the literature on
      chemoresistance-related genes and pathways of multiple cancer types. We then used
      a curated pathway database to investigate significant chemoresistance-related
      biological pathways. In addition, to investigate the importance of
      chemoresistance-related markers in protein-protein interaction networks
      identified using the curated database, we used a gene-ranking algorithm designed
      based on a graph-based scoring function in our previous study. Our comprehensive
      survey and analysis provide a systems biology-based overview of the underlying
      mechanisms of chemoresistance.

PMID- 26220933
TI  - Reassess the t Test: Interact with All Your Data via ANOVA.
AB  - Plant biology is rapidly entering an era where we have the ability to conduct
      intricate studies that investigate how a plant interacts with the entirety of its
      environment. This requires complex, large studies to measure how plant genotypes
      simultaneously interact with a diverse array of environmental stimuli. Successful
      interpretation of the results from these studies requires us to transition away
      from the traditional standard of conducting an array of pairwise t tests toward
      more general linear modeling structures, such as those provided by the extendable
      ANOVA framework. In this Perspective, we present arguments for making this
      transition and illustrate how it will help to avoid incorrect conclusions in
      factorial interaction studies (genotype * genotype, genotype * treatment, and
      treatment * treatment, or higher levels of interaction) that are becoming more
      prevalent in this new era of plant biology. 

PMID- 26220934
TI  - Gains and Losses of Transcription Factor Binding Sites in Saccharomyces
      cerevisiae and Saccharomyces paradoxus.
AB  - Gene expression evolution occurs through changes in cis- or trans-regulatory
      elements or both. Interactions between transcription factors (TFs) and their
      binding sites (TFBSs) constitute one of the most important points where these two
      regulatory components intersect. In this study, we investigated the evolution of
      TFBSs in the promoter regions of different Saccharomyces strains and species. We
      divided the promoter of a gene into the proximal region and the distal region,
      which are defined, respectively, as the 200-bp region upstream of the
      transcription starting site and as the 200-bp region upstream of the proximal
      region. We found that the predicted TFBSs in the proximal promoter regions tend
      to be evolutionarily more conserved than those in the distal promoter regions.
      Additionally, Saccharomyces cerevisiae strains used in the fermentation of
      alcoholic drinks have experienced more TFBS losses than gains compared with
      strains from other environments (wild strains, laboratory strains, and clinical
      strains). We also showed that differences in TFBSs correlate with the cis
      component of gene expression evolution between species (comparing S. cerevisiae
      and its sister species Saccharomyces paradoxus) and within species (comparing two
      closely related S. cerevisiae strains). 

PMID- 26220935
TI  - Rare Events of Intragenus and Intraspecies Horizontal Transfer of the 16S rRNA
      Gene.
AB  - Horizontal gene transfer (HGT) of operational genes has been widely reported in
      prokaryotic organisms. However, informational genes such as those involved in
      transcription and translation processes are very difficult to be horizontally
      transferred, as described by Woese's complexity hypothesis. Here, we analyzed all
      of the completed prokaryotic genome sequences (2,143 genomes) in the NCBI
      (National Center for Biotechnology Information) database, scanned for genomes
      with high intragenomic heterogeneity of 16S rRNA gene copies, and explored
      potential HGT events of ribosomal RNA genes based on the phylogeny, genomic
      organization, and secondary structures of the ribosomal RNA genes. Our results
      revealed 28 genomes with relatively high intragenomic heterogeneity of multiple
      16S rRNA gene copies (lowest pairwise identity <98.0%), and further analysis
      revealed HGT events and potential donors of the heterogeneous copies (such as HGT
      from Chlamydia suis to Chlamydia trachomatis) and mutation events of some
      heterogeneous copies (such as Streptococcus suis JS14). Interestingly, HGT of the
      16S rRNA gene only occurred at intragenus or intraspecies levels, which is quite
      different from the HGT of operational genes. Our results improve our
      understanding regarding the exchange of informational genes. 

PMID- 26220936
TI  - What Fraction of Duplicates Observed in Recently Sequenced Genomes Is Segregating
      and Destined to Fail to Fix?
AB  - Most sequenced eukaryotic genomes show a large excess of recent duplicates. As
      duplicates age, both the population genetic process of failed fixation and the
      mutation-driven process of nonfunctionalization act to reduce the observed number
      of duplicates. Understanding the processes generating the age distributions of
      recent duplicates is important to also understand the role of duplicate genes in
      the functional divergence of genomes. To date, mechanistic models for duplicate
      gene retention only account for the mutation-driven nonfunctionalization process.
      Here, a neutral model for the distribution of synonymous substitutions in
      duplicated genes which are segregating and expected to never fix in a population
      is introduced. This model enables differentiation of neutral loss due to failed
      fixation from loss due to mutation-driven nonfunctionalization. The model has
      been validated on simulated data and subsequent analysis with the model on
      genomic data from human and mouse shows that conclusions about the underlying
      mechanisms for duplicate gene retention can be sensitive to consideration of
      population genetic processes. 

PMID- 26220937
TI  - The Drug-Drug Effects of Rhein on the Pharmacokinetics and Pharmacodynamics of
      Clozapine in Rat Brain Extracellular Fluid by In Vivo Microdialysis.
AB  - Clozapine, an atypical antipsychotic agent, is highly effective in treatment
      resistant schizophrenia; however, its major side effect is constipation. Instead
      of laxatives, rhein is a pharmacologically active component found in Rheum
      palmatum L., a medicinal herbal remedy for constipation. The purpose of this
      study is to determine whether rhein impacts the pharmacokinetics (PK) and
      pharmacodynamics (PD) of clozapine in brain when used to relieve clozapine
      induced constipation. Here, we have investigated not only the PK of clozapine in
      blood but also the effects of rhein on the PK of clozapine in blood and in brain
      extracellular fluid together with the PD effects on neurotransmitters in
      extracellular fluid. The concentrations of clozapine and norclozapine in biologic
      samples were measured by ultra-performance liquid chromatography-tandem mass
      spectrometry. The drug-drug effects of rhein on extracellular neurotransmitter
      efflux in the rat medial prefrontal cortex (mPFC) produced by clozapine were
      assayed by high-performance liquid chromatography-electrochemical detection. The
      results demonstrate that the clozapine PK was nonlinear. Pretreatment with rhein
      for 7 days increased the total blood concentration of clozapine, but
      significantly reduced the unbound clozapine concentrations in the mPFC by
      approximately 3-fold. Furthermore, 7 days of rhein pretreatment thoroughly
      abolished the efflux of dopamine and its metabolite (3,4-dihydroxyphenylacetic
      acid) and altered the profile of homovanillic acid, another metabolite of
      dopamine, in the mPFC. In conclusion, rhein was found to substantially decrease
      clozapine and norclozapine concentrations in the mPFC dialysate, and this is
      accompanied by lower concentrations in the neurotransmitters in the same
      biophase. These findings suggest that a detailed clinical study for drug-drug
      interactions is recommended. 

PMID- 26220938
TI  - Changes in cis-regulatory elements of a key floral regulator are associated with
      divergence of inflorescence architectures.
AB  - Higher plant species diverged extensively with regard to the moment (flowering
      time) and position (inflorescence architecture) at which flowers are formed. This
      seems largely caused by variation in the expression patterns of conserved genes
      that specify floral meristem identity (FMI), rather than changes in the encoded
      proteins. Here, we report a functional comparison of the promoters of homologous
      FMI genes from Arabidopsis, petunia, tomato and Antirrhinum. Analysis of promoter
      reporter constructs in petunia and Arabidopsis, as well as complementation
      experiments, showed that the divergent expression of leafy (LFY) and the petunia
      homolog aberrant leaf and flower (ALF) results from alterations in the upstream
      regulatory network rather than cis-regulatory changes. The divergent expression
      of unusual floral organs (UFO) from Arabidopsis, and the petunia homolog double
      top (DOT), however, is caused by the loss or gain of cis-regulatory promoter
      elements, which respond to trans-acting factors that are expressed in similar
      patterns in both species. Introduction of pUFO:UFO causes no obvious defects in
      Arabidopsis, but in petunia it causes the precocious and ectopic formation of
      flowers. This provides an example of how a change in a cis-regulatory region can
      account for a change in the plant body plan.

PMID- 26220939
TI  - Association between alpha-synuclein blood transcripts and early, neuroimaging
      supported Parkinson's disease.
AB  - There are no cures for neurodegenerative diseases and this is partially due to
      the difficulty of monitoring pathogenic molecules in patients during life. The
      Parkinson's disease gene alpha-synuclein (SNCA) is selectively expressed in blood
      cells and neurons. Here we show that SNCA transcripts in circulating blood cells
      are paradoxically reduced in early stage, untreated and dopamine transporter
      neuroimaging-supported Parkinson's disease in three independent regional,
      national, and international populations representing 500 cases and 363 controls
      and on three analogue and digital platforms with P < 0.0001 in meta-analysis.
      Individuals with SNCA transcripts in the lowest quartile of counts had an odds
      ratio for Parkinson's disease of 2.45 compared to individuals in the highest
      quartile. Disease-relevant transcript isoforms were low even near disease onset.
      Importantly, low SNCA transcript abundance predicted cognitive decline in
      patients with Parkinson's disease during up to 5 years of longitudinal follow-up.
      This study reveals a consistent association of reduced SNCA transcripts in
      accessible peripheral blood and early-stage Parkinson's disease in 863
      participants and suggests a clinical role as potential predictor of cognitive
      decline. Moreover, the three independent biobank cohorts provide a generally
      useful platform for rapidly validating any biological marker of this common
      disease. 

PMID- 26220941
TI  - A new knock-in mouse model of l-DOPA-responsive dystonia.
AB  - Abnormal dopamine neurotransmission is associated with many different genetic and
      acquired dystonic disorders. For instance, mutations in genes critical for the
      synthesis of dopamine, including GCH1 and TH cause l-DOPA-responsive dystonia.
      Despite evidence that implicates abnormal dopamine neurotransmission in dystonia,
      the precise nature of the pre- and postsynaptic defects that result in dystonia
      are not known. To better understand these defects, we generated a knock-in mouse
      model of l-DOPA-responsive dystonia (DRD) mice that recapitulates the human
      p.381Q>K TH mutation (c.1141C>A). Mice homozygous for this mutation displayed the
      core features of the human disorder, including reduced TH activity, dystonia that
      worsened throughout the course of the active phase, and improvement in the
      dystonia in response to both l-DOPA and trihexyphenidyl. Although the gross
      anatomy of the nigrostriatal dopaminergic neurons was normal in DRD mice, the
      microstructure of striatal synapses was affected whereby the ratio of axo-spinous
      to axo-dendritic corticostriatal synaptic contacts was reduced. Microinjection of
      l-DOPA directly into the striatum ameliorated the dystonic movements but
      cerebellar microinjections of l-DOPA had no effect. Surprisingly, the striatal
      dopamine concentration was reduced to ~1% of normal, a concentration more
      typically associated with akinesia, suggesting that (mal)adaptive postsynaptic
      responses may also play a role in the development of dystonia. Administration of
      D1- or D2-like dopamine receptor agonists to enhance dopamine signalling reduced
      the dystonic movements, whereas administration of D1- or D2-like dopamine
      receptor antagonists to further reduce dopamine signalling worsened the dystonia,
      suggesting that both receptors mediate the abnormal movements. Further, D1
      dopamine receptors were supersensitive; adenylate cyclase activity, locomotor
      activity and stereotypy were exaggerated in DRD mice in response to the D1
      dopamine receptor agonist SKF 81297. D2-dopamine receptors exhibited a change in
      the valence in DRD mice with an increase in adenylate cyclase activity and
      blunted behavioural responses after challenge with the D2-dopamine receptor
      agonist quinpirole. Together, our findings suggest that the development of
      dystonia may depend on a reduction in dopamine in combination with specific
      abnormal receptor responses. 

PMID- 26220942
TI  - Early maturation and distinct tau pathology in induced pluripotent stem cell
      derived neurons from patients with MAPT mutations.
AB  - Tauopathies, such as Alzheimer's disease, some cases of frontotemporal dementia,
      corticobasal degeneration and progressive supranuclear palsy, are characterized
      by aggregates of the microtubule-associated protein tau, which are linked to
      neuronal death and disease development and can be caused by mutations in the MAPT
      gene. Six tau isoforms are present in the adult human brain and they differ by
      the presence of 3(3R) or 4(4R) C-terminal repeats. Only the shortest 3R isoform
      is present in foetal brain. MAPT mutations found in human disease affect tau
      binding to microtubules or the 3R:4R isoform ratio by altering exon 10 splicing.
      We have differentiated neurons from induced pluripotent stem cells derived from
      fibroblasts of controls and patients with N279K and P301L MAPT mutations. Induced
      pluripotent stem cell-derived neurons recapitulate developmental tau expression,
      showing the adult brain tau isoforms after several months in culture. Both N279K
      and P301L neurons exhibit earlier electrophysiological maturation and altered
      mitochondrial transport compared to controls. Specifically, the N279K neurons
      show abnormally premature developmental 4R tau expression, including changes in
      the 3R:4R isoform ratio and AT100-hyperphosphorylated tau aggregates, while P301L
      neurons are characterized by contorted processes with varicosity-like structures,
      some containing both alpha-synuclein and 4R tau. The previously unreported faster
      maturation of MAPT mutant human neurons, the developmental expression of 4R tau
      and the morphological alterations may contribute to disease development. 

PMID- 26220943
TI  - Using Histopathologic Evidence to Differentiate Reproductive Senescence from
      Xenobiotic Effects in Middle-aged Female Sprague-Dawley Rats.
AB  - The female reproductive cycle is orchestrated by cyclical and coordinated
      hormonal changes under the direction of the hypothalamic-pituitary-gonadal (HPG)
      axis. Any disruption of the HPG axis may lead to functional and structural
      alterations in the female reproductive system. Test article-related disturbances
      in the estrous cycle can be recognized in nonclinical toxicity studies by staging
      the cycle based on microscopic evaluation of female reproductive organs. In
      chronic rat toxicity studies, an additional complication is the development of
      reproductive senescence, which is associated with natural alterations in the
      reproductive cycle leading to changes in the female reproductive system that can
      potentially be confused with test article effects. The current article describes
      the features of persistent estrus, one stage of reproductive senescence, in
      middle-aged Sprague-Dawley rats and discusses elements to help differentiate
      senescence from induced effects. 

PMID- 26220944
TI  - Juvenile Toxicology: Relevance and Challenges for Toxicologists and Pathologists.
AB  - The Society of Toxicologic Pathology (STP) Education Committee and the STP
      Reproductive Special Interest Group held a North Carolina regional meeting
      entitled, "Juvenile Toxicology: Relevance and Challenges for Toxicologists and
      Pathologists" on March 13, 2015, at the National Institute of Environmental
      Health Sciences/National Toxicology Program in Research Triangle Park, North
      Carolina. The purpose of this regional meeting was to familiarize attendees with
      the topic of juvenile toxicity testing and discuss its relevance to clinical
      pediatric medicine, regulatory perspectives, challenges of appropriate study
      design confronted by toxicologists, and challenges of histopathologic examination
      and interpretation of juvenile tissues faced by pathologists. The 1-day meeting
      was a success with over 60 attendees representing industry, government, research
      organizations, and academia. 

PMID- 26220946
TI  - Vitamin D and Cancer: Diversity, Complexity, and Still a Ways to Go.
AB  - Vitamin D has taken a center-stage role in our basic and population research
      quest for the panacea for all human maladies, including cancer, yet sufficient
      evidence for a beneficial role has existed only for bone health. This Commentary
      discusses and places into a broader context the report of Chandler and colleagues
      that found a protective association for higher vitamin D status in colorectal
      cancer in women, consistent with most other cohort studies but not with limited
      supplementation trial data. Little human evidence exists for the preventive
      potential in other malignancies, including breast cancer, with the exception of
      possible benefit in bladder cancer and an adverse serologic association with
      prostate cancer (pancreatic cancer risk may be similarly influenced) that is
      supported by vitamin D genetic data. Current vitamin D trials are examining high
      dose supplementation (i.e., 1,600-3,333 IU daily) for effects on multiple
      outcomes, but they may not have sufficient power to test efficacy in colorectal
      or other specific malignancies and are unlikely to inform any benefit for higher
      physiologic levels. A more complete understanding of vitamin D and human
      carcinogenesis will come from multifaceted lines of research, including
      elucidation of organ site-specific biologic mechanisms, prospective serologic
      analyses, testing of vitamin D-related genetic variation, and short-term clinical
      metabolic biomarker studies of multidose vitamin D supplementation, including
      metabolomic profiling of controlled supplementation in these and past or ongoing
      trials.

PMID- 26220945
TI  - Fasting until noon triggers increased postprandial hyperglycemia and impaired
      insulin response after lunch and dinner in individuals with type 2 diabetes: a
      randomized clinical trial.
AB  - OBJECTIVE: Skipping breakfast has been consistently associated with high HbA1c
      and postprandial hyperglycemia (PPHG) in patients with type 2 diabetes. Our aim
      was to explore the effect of skipping breakfast on glycemia after a subsequent
      isocaloric (700 kcal) lunch and dinner. RESEARCH DESIGN AND METHODS: In a
      crossover design, 22 patients with diabetes with a mean diabetes duration of 8.4
      +/- 0.7 years, age 56.9 +/- 1.0 years, BMI 28.2 +/- 0.6 kg/m(2), and HbA1c 7.7 +/
      0.1% (61 +/- 0.8 mmol/mol) were randomly assigned to two test days: one day with
      breakfast, lunch, and dinner (YesB) and another with lunch and dinner but no
      breakfast (NoB). Postprandial plasma glucose, insulin, C-peptide, free fatty
      acids (FFA), glucagon, and intact glucagon-like peptide-1 (iGLP-1) were assessed.
      RESULTS: Compared with YesB, lunch area under the curves for 0-180 min (AUC0-180)
      for plasma glucose, FFA, and glucagon were 36.8, 41.1, and 14.8% higher,
      respectively, whereas the AUC0-180 for insulin and iGLP-1 were 17% and 19% lower,
      respectively, on the NoB day (P < 0.0001). Similarly, dinner AUC0-180 for
      glucose, FFA, and glucagon were 26.6, 29.6, and 11.5% higher, respectively, and
      AUC0-180 for insulin and iGLP-1 were 7.9% and 16.5% lower on the NoB day compared
      with the YesB day (P < 0.0001). Furthermore, insulin peak was delayed 30 min
      after lunch and dinner on the NoB day compared with the YesB day. CONCLUSIONS:
      Skipping breakfast increases PPHG after lunch and dinner in association with
      lower iGLP-1 and impaired insulin response. This study shows a long-term
      influence of breakfast on glucose regulation that persists throughout the day.
      Breakfast consumption could be a successful strategy for reduction of PPHG in
      type 2 diabetes.

PMID- 26220947
TI  - The Microbiome: The Trillions of Microorganisms That Maintain Health and Cause
      Disease in Humans and Companion Animals.
AB  - The microbiome is the complex collection of microorganisms, their genes, and
      their metabolites, colonizing the human and animal mucosal surfaces, digestive
      tract, and skin. It is now well known that the microbiome interacts with its
      host, assisting in digestion and detoxification, supporting immunity, protecting
      against pathogens, and maintaining health. Studies published to date have
      demonstrated that healthy individuals are often colonized with different
      microbiomes than those with disease involving various organ systems. This review
      covers a brief history of the development of the microbiome field, the main
      objectives of the Human Microbiome Project, and the most common microbiomes
      inhabiting the human respiratory tract, companion animal digestive tract, and
      skin in humans and companion animals. The main changes in the microbiomes in
      patients with pulmonary, gastrointestinal, and cutaneous lesions are described. 

PMID- 26220948
TI  - Human Liver Cytochrome P450 Enzymes and Microsomal Thiol Methyltransferase Are
      Involved in the Stereoselective Formation and Methylation of the
      Pharmacologically Active Metabolite of Clopidogrel.
AB  - Clopidogrel, a thienopyridine antiplatelet prodrug, is metabolized by oxidation
      to 2-oxo-clopidogrel, followed by conversion to its pharmacologically active
      thiol metabolite. After oral administration of clopidogrel to humans, two thiol
      isomers (H3 and H4) are observed in plasma, with similar concentrations, and only
      H4 is active in humans. In this work, the mechanism of stereoselectivity in the
      formation and S-methylation of H3 and H4 was investigated in vitro. The two
      diastereomers of 2-oxo-clopidogrel were epimerized rapidly at physiologic pH. The
      intrinsic clearance (CLint) for H3 formation from 2-oxo-clopidogrel in human
      liver microsomes (HLMs) was 3.1-fold higher than that for H4 formation,
      indicating stereoselective metabolism. Kinetic studies using expressed enzymes
      demonstrated that the contributions of CYP2B6, CYP2C19, and CYP3A4 to the
      formation of H4 from 2-oxo-clopidogrel were 18.5%, 26.1%, and 53.5%,
      respectively. The CLint ratios of H3 formation to H4 formation from 2-oxo
      clopidogrel by CYP2B6, CYP2C19, and CYP3A4 were 2.2, 1.0, and 1.7, respectively.
      In HLMs, H3 and H4 were further S-methylated, and the S-methylation was inhibited
      by 2,3-dichloromethyl benzylamine, indicating the involvement of thiol S
      methyltransferase. The CLint value for the S-methylation of H3 in HLMs was 98.1
      fold higher than that for H4. The stereoselective formation of H3 from 2-oxo
      clopidogrel and the stereoselective S-methylation of H3 may lead to the similar
      exposure levels of H3 and H4 previously reported in humans. The epimerization of
      2-oxo-clopidogrel and the variations of thiol S-methyltransferase may affect the
      exposure to H4 in humans.

PMID- 26220949
TI  - Over-expression of recombinant proteins with N-terminal His-tag via subcellular
      uneven distribution in Escherichia coli.

PMID- 26220950
TI  - Overexpression of ARGOS Genes Modifies Plant Sensitivity to Ethylene, Leading to
      Improved Drought Tolerance in Both Arabidopsis and Maize.
AB  - Lack of sufficient water is a major limiting factor to crop production worldwide,
      and the development of drought-tolerant germplasm is needed to improve crop
      productivity. The phytohormone ethylene modulates plant growth and development as
      well as plant response to abiotic stress. Recent research has shown that
      modifying ethylene biosynthesis and signaling can enhance plant drought
      tolerance. Here, we report novel negative regulators of ethylene signal
      transduction in Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). These
      regulators are encoded by the ARGOS gene family. In Arabidopsis, overexpression
      of maize ARGOS1 (ZmARGOS1), ZmARGOS8, Arabidopsis ARGOS homolog ORGAN SIZE
      RELATED1 (AtOSR1), and AtOSR2 reduced plant sensitivity to ethylene, leading to
      enhanced drought tolerance. RNA profiling and genetic analysis suggested that the
      ZmARGOS1 transgene acts between an ethylene receptor and CONSTITUTIVE TRIPLE
      RESPONSE1 in the ethylene signaling pathway, affecting ethylene perception or the
      early stages of ethylene signaling. Overexpressed ZmARGOS1 is localized to the
      endoplasmic reticulum and Golgi membrane, where the ethylene receptors and the
      ethylene signaling protein ETHYLENE-INSENSITIVE2 and REVERSION-TO-ETHYLENE
      SENSITIVITY1 reside. In transgenic maize plants, overexpression of ARGOS genes
      also reduces ethylene sensitivity. Moreover, field testing showed that
      UBIQUITIN1:ZmARGOS8 maize events had a greater grain yield than nontransgenic
      controls under both drought stress and well-watered conditions. 

PMID- 26220951
TI  - The VQ Motif-Containing Protein Family of Plant-Specific Transcriptional
      Regulators.
AB  - The VQ motif-containing proteins (designated as VQ proteins) are a class of plant
      specific proteins with a conserved and single short FxxhVQxhTG amino acid
      sequence motif. VQ proteins regulate diverse developmental processes, including
      responses to biotic and abiotic stresses, seed development, and
      photomorphogenesis. In this Update, we summarize and discuss recent advances in
      our understanding of the regulation and function of VQ proteins and the role of
      the VQ motif in mediating transcriptional regulation and protein-protein
      interactions in signaling pathways. Based on the accumulated evidence, we propose
      a general mechanism of action for the VQ protein family, which likely defines a
      novel class of transcriptional regulators specific to plants. 

PMID- 26220940
TI  - Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects.
AB  - In a large multicentre sample of cognitively normal subjects, as a function of
      age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal
      fluid levels of Alzheimer's disease biomarkers including: total tau,
      phosphorylated tau and amyloid-beta1-42. Fifteen cohorts from 12 different
      centres with either enzyme-linked immunosorbent assays or Luminex(r) measurements
      were selected for this study. Each centre sent nine new cerebrospinal fluid
      aliquots that were used to measure total tau, phosphorylated tau and amyloid
      beta1-42 in the Gothenburg laboratory. Seven centres showed a high correlation
      with the new Gothenburg measurements; therefore, 10 cohorts from these centres
      are included in the analyses here (1233 healthy control subjects, 40-84 years
      old). Amyloid-beta amyloid status (negative or positive) and neurodegeneration
      status (negative or positive) was established based on the pathological
      cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid
      amyloid-beta1-42 and total tau, respectively. While gender did not affect these
      biomarker values, APOE genotype modified the age-associated changes in
      cerebrospinal fluid biomarkers such that APOE epsilon4 carriers showed stronger
      age-related changes in cerebrospinal fluid phosphorylated tau, total tau and
      amyloid-beta1-42 values and APOE epsilon2 carriers showed the opposite effect. At
      40 years of age, 76% of the subjects were classified as amyloid negative,
      neurodegeneration negative and their frequency decreased to 32% at 85 years. The
      amyloid-positive neurodegeneration-negative group remained stable. The amyloid
      negative neurodegeneration-positive group frequency increased slowly from 1% at
      44 years to 16% at 85 years, but its frequency was not affected by APOE genotype.
      The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53
      years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-beta1-42
      levels were already frequent in midlife and APOE genotype strongly affects the
      levels of cerebrospinal fluid amyloid-beta1-42, phosphorylated tau and total tau
      across the lifespan without influencing the frequency of subjects with suspected
      non-amyloid pathology. 

PMID- 26220952
TI  - A Novel Gene, OZONE-RESPONSIVE APOPLASTIC PROTEIN1, Enhances Cell Death in Ozone
      Stress in Rice.
AB  - A novel protein, OZONE-RESPONSIVE APOPLASTIC PROTEIN1 (OsORAP1), was
      characterized, which was previously suggested as a candidate gene underlying
      OzT9, a quantitative trait locus for ozone stress tolerance in rice (Oryza
      sativa). The sequence of OsORAP1 was similar to that of ASCORBATE OXIDASE (AO)
      proteins. It was localized in the apoplast, as shown by transient expression of
      an OsORAP1/green fluorescent protein fusion construct in Nicotiana benthamiana
      leaf epidermal and mesophyll cells, but did not possess AO activity, as shown by
      heterologous expression of OsORAP1 in Arabidopsis (Arabidopsis thaliana) mutants
      with reduced background AO activity. A knockout rice line of OsORAP1 showed
      enhanced tolerance to ozone stress (120 nL L(-1) average daytime concentration,
      20 d), as demonstrated by less formation of leaf visible symptoms (i.e. cell
      death), less lipid peroxidation, and lower NADPH oxidase activity, indicating
      reduced active production of reactive oxygen species. In contrast, the effect of
      ozone on chlorophyll content was not significantly different among the lines.
      These observations suggested that OsORAP1 specifically induced cell death in
      ozone stress. Significantly enhanced expression of jasmonic acid-responsive genes
      in the knockout line implied the involvement of the jasmonic acid pathway in
      symptom mitigation. Sequence analysis revealed extensive polymorphisms in the
      promoter region of OsORAP1 between the ozone-susceptible cv Nipponbare and the
      ozone-tolerant cv Kasalath, the OzT9 donor variety, which could be responsible
      for the differential regulation of OsORAP1 reported earlier. These pieces of
      evidence suggested that OsORAP1 enhanced cell death in ozone stress, and its
      expression levels could explain the effect of a previously reported quantitative
      trait locus. 

PMID- 26220953
TI  - MUCILAGE-RELATED10 Produces Galactoglucomannan That Maintains Pectin and
      Cellulose Architecture in Arabidopsis Seed Mucilage.
AB  - Plants invest a lot of their resources into the production of an extracellular
      matrix built of polysaccharides. While the composition of the cell wall is
      relatively well characterized, the functions of the individual polymers and the
      enzymes that catalyze their biosynthesis remain poorly understood. We exploited
      the Arabidopsis (Arabidopsis thaliana) seed coat epidermis (SCE) to study cell
      wall synthesis. SCE cells produce mucilage, a specialized secondary wall that is
      rich in pectin, at a precise stage of development. A coexpression search for
      MUCILAGE-RELATED (MUCI) genes identified MUCI10 as a key determinant of mucilage
      properties. MUCI10 is closely related to a fenugreek (Trigonella foenumgraecum)
      enzyme that has in vitro galactomannan alpha-1,6-galactosyltransferase activity.
      Our detailed analysis of the muci10 mutants demonstrates that mucilage contains
      highly branched galactoglucomannan (GGM) rather than unbranched glucomannan.
      MUCI10 likely decorates glucomannan, synthesized by CELLULOSE SYNTHASE-LIKE A2,
      with galactose residues in vivo. The degree of galactosylation is essential for
      the synthesis of the GGM backbone, the structure of cellulose, mucilage density,
      as well as the adherence of pectin. We propose that GGM scaffolds control
      mucilage architecture along with cellulosic rays and show that Arabidopsis SCE
      cells represent an excellent model in which to study the synthesis and function
      of GGM. Arabidopsis natural varieties with defects similar to muci10 mutants may
      reveal additional genes involved in GGM synthesis. Since GGM is the most abundant
      hemicellulose in the secondary walls of gymnosperms, understanding its
      biosynthesis may facilitate improvements in the production of valuable
      commodities from softwoods. 

PMID- 26220955
TI  - Restrictive red blood cell transfusion strategies appear safe in most clinical
      settings.

PMID- 26220956
TI  - CT coronary angiography increases diagnostic certainty in patients with stable
      chest pain.

PMID- 26220954
TI  - The Use of Contact Mode Atomic Force Microscopy in Aqueous Medium for Structural
      Analysis of Spinach Photosynthetic Complexes.
AB  - To investigate the dynamics of photosynthetic pigment-protein complexes in
      vascular plants at high resolution in an aqueous environment, membrane-protruding
      oxygen-evolving complexes (OECs) associated with photosystem II (PSII) on spinach
      (Spinacia oleracea) grana membranes were examined using contact mode atomic force
      microscopy. This study represents, to our knowledge, the first use of atomic
      force microscopy to distinguish the putative large extrinsic loop of Photosystem
      II CP47 reaction center protein (CP47) from the putative oxygen-evolving enhancer
      proteins 1, 2, and 3 (PsbO, PsbP, and PsbQ) and large extrinsic loop of
      Photosystem II CP43 reaction center protein (CP43) in the PSII-OEC extrinsic
      domains of grana membranes under conditions resulting in the disordered
      arrangement of PSII-OEC particles. Moreover, we observed uncharacterized membrane
      particles that, based on their physical characteristics and electrophoretic
      analysis of the polypeptides associated with the grana samples, are hypothesized
      to be a domain of photosystem I that protrudes from the stromal face of single
      thylakoid bilayers. Our results are interpreted in the context of the results of
      others that were obtained using cryo-electron microscopy (and single particle
      analysis), negative staining and freeze-fracture electron microscopy, as well as
      previous atomic force microscopy studies. 

PMID- 26220957
TI  - Personalised chronic care planning shows limited but promising effects on
      physical and psychological health and self-management capabilities.

PMID- 26220959
TI  - FermiKit: assembly-based variant calling for Illumina resequencing data.
AB  - FermiKit is a variant calling pipeline for Illumina whole-genome germline data.
      It de novo assembles short reads and then maps the assembly against a reference
      genome to call SNPs, short insertions/deletions and structural variations.
      FermiKit takes about one day to assemble 30-fold human whole-genome data on a
      modern 16-core server with 85 GB RAM at the peak, and calls variants in half an
      hour to an accuracy comparable to the current practice. FermiKit assembly is a
      reduced representation of raw data while retaining most of the original
      information. AVAILABILITY AND IMPLEMENTATION: https://github.com/lh3/fermikit
      CONTACT: hengli@broadinstitute.org.

PMID- 26220958
TI  - Clopidogrel Enhances Mesenchymal Stem Cell Proliferation Following Periodontitis.
AB  - Bone formation is dependent on the differentiation of osteoblasts from
      mesenchymal stem cells (MSCs). In addition to serving as progenitors, MSCs reduce
      inflammation and produce factors that stimulate tissue formation. Upon injury,
      MSCs migrate to the periodontium, where they contribute to regeneration. We
      examined the effect of clopidogrel and aspirin on MSCs following induction of
      periodontitis in rats by placement of ligatures. We showed that after the removal
      of ligatures, which induces resolution of periodontal inflammation, clopidogrel
      had a significant effect on reducing the inflammatory infiltrate. It also
      increased the number of osteoblasts and MSCs. Mechanistically, the latter was
      linked to increased proliferation of MSCs in vivo and in vitro. When given prior
      to inducing periodontitis, clopidogrel had little effect on MSC or osteoblasts
      numbers. Applying aspirin before or after induction of periodontitis did not have
      a significant effect on the parameters measured. These results suggest that
      clopidogrel may have a positive effect on MSCs in conditions where a reparative
      process has been initiated. 

PMID- 26220960
TI  - Canonical, stable, general mapping using context schemes.
AB  - MOTIVATION: Sequence mapping is the cornerstone of modern genomics. However, most
      existing sequence mapping algorithms are insufficiently general. RESULTS: We
      introduce context schemes: a method that allows the unambiguous recognition of a
      reference base in a query sequence by testing the query for substrings from an
      algorithmically defined set. Context schemes only map when there is a unique best
      mapping, and define this criterion uniformly for all reference bases. Mappings
      under context schemes can also be made stable, so that extension of the query
      string (e.g. by increasing read length) will not alter the mapping of previously
      mapped positions. Context schemes are general in several senses. They natively
      support the detection of arbitrary complex, novel rearrangements relative to the
      reference. They can scale over orders of magnitude in query sequence length.
      Finally, they are trivially extensible to more complex reference structures, such
      as graphs, that incorporate additional variation. We demonstrate empirically the
      existence of high-performance context schemes, and present efficient context
      scheme mapping algorithms. AVAILABILITY AND IMPLEMENTATION: The software test
      framework created for this study is available from
      https://registry.hub.docker.com/u/adamnovak/sequence-graphs/. CONTACT:
      anovak@soe.ucsc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 26220961
TI  - Designing alternative splicing RNA-seq studies. Beyond generic guidelines.
AB  - MOTIVATION: Designing an RNA-seq study depends critically on its specific goals,
      technology and underlying biology, which renders general guidelines inadequate.
      We propose a Bayesian framework to customize experiments so that goals can be
      attained and resources are not wasted, with a focus on alternative splicing.
      RESULTS: We studied how read length, sequencing depth, library preparation and
      the number of replicates affects cost-effectiveness of single-sample and group
      comparison studies. Optimal settings varied strongly according to the target
      organism or tissue (potential 50-500% cost cuts) and, interestingly, short reads
      outperformed long reads for standard analyses. Our framework learns key
      characteristics for study design from the data, and predicts if and how to
      continue experimentation. These predictions matched several follow-up
      experimental datasets that were used for validation. We provide default
      pipelines, but the framework can be combined with other data analysis methods and
      can help assess their relative merits. AVAILABILITY AND IMPLEMENTATION: casper
      package at www.bioconductor.org/packages/release/bioc/html/casper.html,
      Supplementary Manual by typing casperDesign() at the R prompt. CONTACT:
      rosselldavid@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 26220962
TI  - MetTailor: dynamic block summary and intensity normalization for robust analysis
      of mass spectrometry data in metabolomics.
AB  - MOTIVATION: Accurate cross-sample peak alignment and reliable intensity
      normalization is a critical step for robust quantitative analysis in untargetted
      metabolomics since tandem mass spectrometry (MS/MS) is rarely used for compound
      identification. Therefore shortcomings in the data processing steps can easily
      introduce false positives due to misalignments and erroneous normalization
      adjustments in large sample studies. RESULTS: In this work, we developed a
      software package MetTailor featuring two novel data preprocessing steps to remedy
      drawbacks in the existing processing tools. First, we propose a novel dynamic
      block summarization (DBS) method for correcting misalignments from peak alignment
      algorithms, which alleviates missing data problem due to misalignments. For the
      purpose of verifying correct re-alignments, we propose to use the cross-sample
      consistency in isotopic intensity ratios as a quality metric. Second, we
      developed a flexible intensity normalization procedure that adjusts normalizing
      factors against the temporal variations in total ion chromatogram (TIC) along the
      chromatographic retention time (RT). We first evaluated the DBS algorithm using a
      curated metabolomics dataset, illustrating that the algorithm identifies
      misaligned peaks and correctly realigns them with good sensitivity. We next
      demonstrated the DBS algorithm and the RT-based normalization procedure in a
      large-scale dataset featuring >100 sera samples in primary Dengue infection
      study. Although the initial alignment was successful for the majority of peaks,
      the DBS algorithm still corrected ~7000 misaligned peaks in this data and many
      recovered peaks showed consistent isotopic patterns with the peaks they were
      realigned to. In addition, the RT-based normalization algorithm efficiently
      removed visible local variations in TIC along the RT, without sacrificing the
      sensitivity of detecting differentially expressed metabolites. AVAILABILITY AND
      IMPLEMENTATION: The R package MetTailor is freely available at the SourceForge
      website http://mettailor.sourceforge.net/. CONTACT: hyung_won_choi@nuhs.edu.sg
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 26220963
TI  - Bacterial Cell Enlargement Requires Control of Cell Wall Stiffness Mediated by
      Peptidoglycan Hydrolases.
AB  - Most bacterial cells are enclosed in a single macromolecule of the cell wall
      polymer, peptidoglycan, which is required for shape determination and maintenance
      of viability, while peptidoglycan biosynthesis is an important antibiotic target.
      It is hypothesized that cellular enlargement requires regional expansion of the
      cell wall through coordinated insertion and hydrolysis of peptidoglycan. Here, a
      group of (apparent glucosaminidase) peptidoglycan hydrolases are identified that
      are together required for cell enlargement and correct cellular morphology of
      Staphylococcus aureus, demonstrating the overall importance of this enzyme
      activity. These are Atl, SagA, ScaH, and SagB. The major advance here is the
      explanation of the observed morphological defects in terms of the mechanical and
      biochemical properties of peptidoglycan. It was shown that cells lacking groups
      of these hydrolases have increased surface stiffness and, in the absence of SagB,
      substantially increased glycan chain length. This indicates that, beyond their
      established roles (for example in cell separation), some hydrolases enable
      cellular enlargement by making peptidoglycan easier to stretch, providing the
      first direct evidence demonstrating that cellular enlargement occurs via
      modulation of the mechanical properties of peptidoglycan. IMPORTANCE:
      Understanding bacterial growth and division is a fundamental problem, and
      knowledge in this area underlies the treatment of many infectious diseases.
      Almost all bacteria are surrounded by a macromolecule of peptidoglycan that
      encloses the cell and maintains shape, and bacterial cells must increase the size
      of this molecule in order to enlarge themselves. This requires not only the
      insertion of new peptidoglycan monomers, a process targeted by antibiotics,
      including penicillin, but also breakage of existing bonds, a potentially
      hazardous activity for the cell. Using Staphylococcus aureus, we have identified
      a set of enzymes that are critical for cellular enlargement. We show that these
      enzymes are required for normal growth and define the mechanism through which
      cellular enlargement is accomplished, i.e., by breaking bonds in the
      peptidoglycan, which reduces the stiffness of the cell wall, enabling it to
      stretch and expand, a process that is likely to be fundamental to many bacteria.

PMID- 26220964
TI  - Pediatric Cystic Fibrosis Sputum Can Be Chemically Dynamic, Anoxic, and Extremely
      Reduced Due to Hydrogen Sulfide Formation.
AB  - Severe and persistent bacterial lung infections characterize cystic fibrosis
      (CF). While several studies have documented the microbial diversity within CF
      lung mucus, we know much less about the inorganic chemistry that constrains
      microbial metabolic processes and their distribution. We hypothesized that sputum
      is chemically heterogeneous both within and between patients. To test this, we
      measured microprofiles of oxygen and sulfide concentrations as well as pH and
      oxidation-reduction potentials in 48 sputum samples from 22 pediatric patients
      with CF. Inorganic ions were measured in 20 samples from 12 patients. In all
      cases, oxygen was depleted within the first few millimeters below the sputum-air
      interface. Apart from this steep oxycline, anoxia dominated the sputum
      environment. Different sputum samples exhibited a broad range of redox
      conditions, with either oxidizing (16 mV to 355 mV) or reducing (-300 to -107 mV)
      potentials. The majority of reduced samples contained hydrogen sulfide and had a
      low pH (2.9 to 6.5). Sulfide concentrations increased at a rate of 0.30 uM
      H2S/min. Nitrous oxide was detected in only one sample that also contained
      sulfide. Microenvironmental variability was observed both within a single patient
      over time and between patients. Modeling oxygen dynamics within CF mucus plugs
      indicates that anoxic zones vary as a function of bacterial load and mucus
      thickness and can occupy a significant portion of the mucus volume. Thus, aerobic
      respiration accounts only partially for pathogen survival in CF sputum,
      motivating research to identify mechanisms of survival under conditions that span
      fluctuating redox states, including sulfidic environments. IMPORTANCE: Microbial
      infections are the major cause of morbidity and mortality in people living with
      CF, and yet microbial growth and survival in CF airways are not well understood.
      Insufficient information about the chemistry of the in vivo environment
      contributes to this knowledge gap. Our documentation of variable redox states
      corresponding to the presence or absence of sulfide begins to fill this void and
      motivates understanding of how different opportunistic pathogens adapt in these
      dynamic environments. Given the changing chemical state of CF sputum over time,
      it is important to consider a spectrum of aerobic and anaerobic lifestyles when
      studying CF pathogens in the laboratory. This work not only provides relevant
      constraints that can shape the design of laboratory experiments, it also suggests
      that sulfide might be a useful proxy for assessing the redox state of sputum in
      the clinic.

PMID- 26220965
TI  - Structured and Dynamic Disordered Domains Regulate the Activity of a
      Multifunctional Anti-sigma Factor.
AB  - The anti-sigma factor NepR plays a central role in regulation of the general
      stress response (GSR) in alphaproteobacteria. This small protein has two known
      interaction partners: its cognate extracytoplasmic function (ECF) sigma factor
      and the anti-anti-sigma factor, PhyR. Stress-dependent phosphorylation of PhyR
      initiates a protein partner switch that promotes phospho-PhyR binding to NepR,
      which frees ECF sigma to activate transcription of genes required for cell
      survival under adverse or fluctuating conditions. We have defined key functional
      roles for structured and intrinsically disordered domains of Caulobacter
      crescentus NepR in partner binding and activation of GSR transcription. We
      further demonstrate that NepR strongly stimulates the rate of PhyR
      phosphorylation in vitro and that this effect requires the structured and
      disordered domains of NepR. This result provides evidence for an additional layer
      of GSR regulation in which NepR directly influences activation of its binding
      partner, PhyR, as an anti-anti-sigma factor. We conclude that structured and
      intrinsically disordered domains of NepR coordinately control multiple functions
      in the GSR signaling pathway, including core protein partner switch interactions
      and pathway activation by phosphorylation. IMPORTANCE: Anti-sigma factors are key
      molecular participants in a range of adaptive responses in bacteria. The anti
      sigma factor NepR plays a vital role in a multiprotein partner switch that
      governs general stress response (GSR) transcription in alphaproteobacteria. We
      have defined conserved and unconserved features of NepR structure that determine
      its function as an anti-sigma factor and uncovered a functional role for
      intrinsically disordered regions of NepR in partner binding events required for
      GSR activation. We further demonstrate a novel function for NepR as an enhancer
      of PhyR phosphorylation; this activity also requires the disordered domains of
      NepR. Our results provide evidence for a new layer of GSR regulatory control in
      which NepR directly modulates PhyR phosphorylation and, hence, activation of the
      GSR.

PMID- 26220966
TI  - Genomic Adaptations to the Loss of a Conserved Bacterial DNA Methyltransferase.
AB  - CcrM is an orphan DNA methyltransferase nearly universally conserved in a vast
      group of Alphaproteobacteria. In Caulobacter crescentus, it controls the
      expression of key genes involved in the regulation of the cell cycle and cell
      division. Here, we demonstrate, using an experimental evolution approach, that C.
      crescentus can significantly compensate, through easily accessible genetic
      changes like point mutations, the severe loss in fitness due to the absence of
      CcrM, quickly improving its growth rate and cell morphology in rich medium. By
      analyzing the compensatory mutations genome-wide in 12 clones sampled from
      independent DeltaccrM populations evolved for ~300 generations, we demonstrated
      that each of the twelve clones carried at least one mutation that potentially
      stimulated ftsZ expression, suggesting that the low intracellular levels of FtsZ
      are the major burden of DeltaccrM mutants. In addition, we demonstrate that the
      phosphoenolpyruvate-carbohydrate phosphotransfer system (PTS) actually modulates
      ftsZ and mipZ transcription, uncovering a previously unsuspected link between
      metabolic regulation and cell division in Alphaproteobacteria. We present
      evidence that point mutations found in genes encoding proteins of the PTS provide
      the strongest fitness advantage to DeltaccrM cells cultivated in rich medium
      despite being disadvantageous in minimal medium. This environmental sign
      epistasis might prevent such mutations from getting fixed under changing natural
      conditions, adding a plausible explanation for the broad conservation of CcrM.
      IMPORTANCE: In bacteria, DNA methylation has a variety of functions, including
      the control of DNA replication and/or gene expression. The cell cycle-regulated
      DNA methyltransferase CcrM modulates the transcription of many genes and is
      critical for fitness in Caulobacter crescentus. Here, we used an original
      experimental evolution approach to determine which of its many targets make CcrM
      so important physiologically. We show that populations lacking CcrM evolve
      quickly, accumulating an excess of mutations affecting, directly or indirectly,
      the expression of the ftsZ cell division gene. This finding suggests that the
      most critical function of CcrM in C. crescentus is to promote cell division by
      enhancing FtsZ intracellular levels. During this work, we also discovered an
      unexpected link between metabolic regulation and cell division that might extend
      to other Alphaproteobacteria.

PMID- 26220967
TI  - Molecular Dissection of the Essential Features of the Origin of Replication of
      the Second Vibrio cholerae Chromosome.
AB  - Vibrionaceae family members are interesting models for studying DNA replication
      initiation, as they contain two circular chromosomes. Chromosome II (chrII)
      replication is governed by two evolutionarily unique yet highly conserved
      elements, the origin DNA sequence oriCII and the initiator protein RctB. The
      minimum functional region of oriCII, oriCII-min, contains multiple elements that
      are bound by RctB in vitro, but little is known about the specific requirements
      for individual elements during oriCII initiation. We utilized undirected and site
      specific mutagenesis to investigate the functionality of mutant forms of oriCII
      min and assessed binding to various mutant forms by RctB. Our analyses showed
      that deletions, point mutations, and changes in RctB target site spacing or
      methylation all impaired oriCII-min-based replication. RctB displayed a reduced
      affinity for most of the low-efficacy origins tested, although its characteristic
      cooperative binding was generally maintained. Mutations that removed or altered
      the relative positions of origin components other than RctB binding sites (e.g.,
      AT-rich sequence, DnaA target site) also abolished replicative capacity.
      Comprehensive mutagenesis and deep-sequencing-based screening (OriSeq) allowed
      the identification of a previously uncharacterized methylated domain in oriCII
      that is required for origin function. Together, our results reveal the remarkable
      evolutionary honing of oriCII and provide new insight into the complex interplay
      between RctB and oriCII. IMPORTANCE: The genome of the enteric pathogen Vibrio
      cholerae consists of two chromosomes. While the chromosome I replication origin
      and its cognate replication initiator protein resemble those of Escherichia coli,
      the factors responsible for chromosome II replication initiation display no
      similarity to any other known initiation systems. Here, to enhance our
      understanding of how this DNA sequence, oriCII, and its initiator protein, RctB,
      function, we used both targeted mutagenesis and a new random-mutagenesis approach
      (OriSeq) to finely map the oriCII structural features and sequences required for
      RctB-mediated DNA replication. Collectively, our findings reveal the
      extraordinary evolutionary honing of the architecture and motifs that constitute
      oriCII and reveal a new role for methylation in oriCII-based replication.
      Finally, our findings suggest that the OriSeq approach is likely to be widely
      applicable for defining critical bases in cis-acting sequences.

PMID- 26220968
TI  - Cell Wall Remodeling Enzymes Modulate Fungal Cell Wall Elasticity and Osmotic
      Stress Resistance.
AB  - The fungal cell wall confers cell morphology and protection against environmental
      insults. For fungal pathogens, the cell wall is a key immunological modulator and
      an ideal therapeutic target. Yeast cell walls possess an inner matrix of
      interlinked beta-glucan and chitin that is thought to provide tensile strength
      and rigidity. Yeast cells remodel their walls over time in response to
      environmental change, a process controlled by evolutionarily conserved stress
      (Hog1) and cell integrity (Mkc1, Cek1) signaling pathways. These mitogen
      activated protein kinase (MAPK) pathways modulate cell wall gene expression,
      leading to the construction of a new, modified cell wall. We show that the cell
      wall is not rigid but elastic, displaying rapid structural realignments that
      impact survival following osmotic shock. Lactate-grown Candida albicans cells are
      more resistant to hyperosmotic shock than glucose-grown cells. We show that this
      elevated resistance is not dependent on Hog1 or Mkc1 signaling and that most cell
      death occurs within 10 min of osmotic shock. Sudden decreases in cell volume
      drive rapid increases in cell wall thickness. The elevated stress resistance of
      lactate-grown cells correlates with reduced cell wall elasticity, reflected in
      slower changes in cell volume following hyperosmotic shock. The cell wall
      elasticity of lactate-grown cells is increased by a triple mutation that
      inactivates the Crh family of cell wall cross-linking enzymes, leading to
      increased sensitivity to hyperosmotic shock. Overexpressing Crh family members in
      glucose-grown cells reduces cell wall elasticity, providing partial protection
      against hyperosmotic shock. These changes correlate with structural realignment
      of the cell wall and with the ability of cells to withstand osmotic shock.
      IMPORTANCE: The C. albicans cell wall is the first line of defense against
      external insults, the site of immune recognition by the host, and an attractive
      target for antifungal therapy. Its tensile strength is conferred by a network of
      cell wall polysaccharides, which are remodeled in response to growth conditions
      and environmental stress. However, little is known about how cell wall elasticity
      is regulated and how it affects adaptation to stresses such as sudden changes in
      osmolarity. We show that elasticity is critical for survival under conditions of
      osmotic shock, before stress signaling pathways have time to induce gene
      expression and drive glycerol accumulation. Critical cell wall remodeling enzymes
      control cell wall flexibility, and its regulation is strongly dependent on host
      nutritional inputs. We also demonstrate an entirely new level of cell wall
      dynamism, where significant architectural changes and structural realignment
      occur within seconds of an osmotic shock.

PMID- 26220970
TI  - High-throughput genetic characterization of a cohort of Brugada syndrome
      patients.
AB  - Brugada syndrome (BrS) is an inherited cardiac arrhythmic disorder that can lead
      to sudden death, with a prevalence of 1:5000 in Caucasian population and
      affecting mainly male patients in their third to fourth decade of life. BrS is
      inherited as an autosomal dominant trait; however, to date genetic bases have
      been only partially understood. Indeed most mutations are located in the SCN5A
      gene, encoding the alpha-subunit of the Na(+) cardiac channel, but >70% BrS
      patients still remain genetically undiagnosed. Although 21 other genes have been
      associated with BrS susceptibility, their pathogenic role is still unclear. A
      recent next-generation sequencing study investigated the contribution of 45
      arrhythmia susceptibility genes in BrS pathogenesis, observing a significant
      enrichment only for SCN5A. In our study, we evaluated the distribution of
      putative functional variants in a wider panel of 158 genes previously associated
      with arrhythmic and cardiac defects in a cohort of 91 SCN5A-negative BrS
      patients. In addition, to identify genes significantly enriched in BrS, we
      performed a mutation burden test by using as control dataset European individuals
      selected from the 1000Genomes project. We confirmed BrS genetic heterogeneity and
      identified new potential BrS candidates such as DSG2 and MYH7, suggesting a
      possible genetic overlap between different cardiac disorders. 

PMID- 26220969
TI  - Genomically Informed Surveillance for Carbapenem-Resistant Enterobacteriaceae in
      a Health Care System.
AB  - Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health
      concern. Rapid identification of the resistance genes, their mobilization
      capacity, and strains carrying them is essential to direct hospital resources to
      prevent spread and improve patient outcomes. Whole-genome sequencing allows
      refined tracking of both chromosomal traits and associated mobile genetic
      elements that harbor resistance genes. To enhance surveillance of CREs, clinical
      isolates with phenotypic resistance to carbapenem antibiotics underwent whole
      genome sequencing. Analysis of 41 isolates of Klebsiella pneumoniae and
      Enterobacter cloacae, collected over a 3-year period, identified K. pneumoniae
      carbapenemase (KPC) genes encoding KPC-2, -3, and -4 and OXA-48 carbapenemases.
      All occurred within transposons, including multiple Tn4401 transposon isoforms,
      embedded within more than 10 distinct plasmids representing incompatibility (Inc)
      groups IncR, -N, -A/C, -H, and -X. Using short-read sequencing, draft maps were
      generated of new KPC-carrying vectors, several of which were derivatives of the
      IncN plasmid pBK31551. Two strains also had Tn4401 chromosomal insertions.
      Integrated analyses of plasmid profiles and chromosomal single-nucleotide
      polymorphism (SNP) profiles refined the strain patterns and provided a baseline
      hospital mobilome to facilitate analysis of new isolates. When incorporated with
      patient epidemiological data, the findings identified limited outbreaks against a
      broader 3-year period of sporadic external entry of many different strains and
      resistance vectors into the hospital. These findings highlight the utility of
      genomic analyses in internal and external surveillance efforts to stem the
      transmission of drug-resistant strains within and across health care
      institutions. IMPORTANCE: We demonstrate how detection of resistance genes within
      mobile elements and resistance-carrying strains furthers active surveillance
      efforts for drug resistance. Whole-genome sequencing is increasingly available in
      hospital laboratories and provides a powerful and nuanced means to define the
      local landscape of drug resistance. In this study, isolates of Klebsiella
      pneumoniae and Enterobacter cloacae with resistance to carbapenem antibiotics
      were sequenced. Multiple carbapenemase genes were identified that resided in
      distinct transposons and plasmids. This mobilome, or population of mobile
      elements capable of mobilizing drug resistance, further highlighted the degree of
      strain heterogeneity while providing a detailed timeline of carbapenemase entry
      into the hospital over a 3-year period. These surveillance efforts support
      effective targeting of infection control resources and the development of
      institution-specific repositories of resistance genes and the mobile elements
      that carry them.

PMID- 26220972
TI  - Mutation p.L799R in the LDLR, which affects the transmembrane domain of the LDLR,
      prevents membrane insertion and causes secretion of the mutant LDLR.
AB  - Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial
      hypercholesterolemia (FH). The mechanism by which mutations in the LDLR affecting
      the transmembrane domain of the receptor cause FH has not been thoroughly
      investigated. In this study, we have selected 12 naturally occurring mutations
      affecting the transmembrane domain and studied their effect on the LDLR. The main
      strategy has been to transiently transfect HepG2 cells with mutant LDLR plasmids
      and to study the mutant LDLRs in cell lysates and in media by western blot
      analysis. The most striking finding was that mutation p.L799R led to secretion of
      the entire 160 kDa mature L799R-LDLR. Residue 799Leu is in the middle of the 22
      residue transmembrane domain, and introduction of a basic residue in the
      hydrophobic core of the transmembrane domain could prevent L799R-LDLR from being
      correctly recognized and integrated in the membrane by the Sec61 translocon
      complex. This would then lead to translocation of the entire L799R-LDLR into the
      lumen of the endoplasmic reticulum. Mutation p.L799R should be considered a
      member of a separate class of FH-causing mutations that affects the insertion of
      the LDLR in the cell membrane. 

PMID- 26220971
TI  - Loss of fibulin-4 disrupts collagen synthesis and maturation: implications for
      pathology resulting from EFEMP2 mutations.
AB  - Homozygous recessive mutations in either EFEMP2 (encoding fibulin-4) or FBLN5
      (encoding fibulin-5), critical genes for elastogenesis, lead to autosomal
      recessive cutis laxa types 1B and 1A, respectively. Previously, fibulin-4 was
      shown to bind lysyl oxidase (LOX), an elastin/collagen cross-linking enzyme, in
      vitro. Consistently, reported defects in humans with EFEMP2 mutations are more
      severe and broad in range than those due to FBLN5 mutations and encompass both
      elastin-rich and collagen-rich tissues. However, the underlying disease mechanism
      in EFEMP2 mutations has not been fully addressed. Here, we show that fibulin-4 is
      important for the integrity of aortic collagen in addition to elastin. Smooth
      muscle-specific Efemp2 loss in mouse (termed SMKO) resulted in altered fibrillar
      collagen localization with larger, poorly organized fibrils. LOX activity was
      decreased in Efemp2-null cells, and collagen cross-linking was diminished in SMKO
      aortas; however, elastin cross-linking was unaffected and the level of mature LOX
      was maintained to that of wild-type aortas. Proteomic screening identified
      multiple proteins involved in procollagen processing and maturation as potential
      fibulin-4-binding partners. We showed that fibulin-4 binds procollagen C
      endopeptidase enhancer 1 (Pcolce), which enhances proteolytic cleavage of the
      procollagen C-terminal propeptide during procollagen processing. Interestingly,
      however, procollagen cleavage was not affected by the presence or absence of
      fibulin-4 in vitro. Thus, our data indicate that fibulin-4 serves as a potential
      scaffolding protein during collagen maturation in the extracellular space.
      Analysis of collagen in other tissues affected by fibulin-4 loss should further
      increase our understanding of underlying pathologic mechanisms in patients with
      EFEMP2 mutations. 

PMID- 26220973
TI  - A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of
      the PEX5 long isoform.
AB  - Import of peroxisomal matrix proteins, crucial for peroxisome biogenesis, is
      mediated by the cytosolic receptors PEX5 and PEX7 that recognize proteins
      carrying peroxisomal targeting signals 1 or 2 (PTS1 or PTS2), respectively.
      Mutations in PEX5 or 12 other PEX genes cause peroxisome biogenesis disorders,
      collectively named the Zellweger spectrum disorders (ZSDs), whereas mutations in
      PEX7 cause rhizomelic chondrodysplasia punctata type 1 (RCDP1). Three additional
      RCDP types, RCDP2-3-4, are caused, respectively, by mutations in GNPAT, AGPS and
      FAR1, encoding enzymes involved in plasmalogen biosynthesis. Here we report a
      fifth type of RCDP (RCDP5) caused by a novel mutation in PEX5. In four patients
      with RCDP from two independent families, we identified a homozygous frame shift
      mutation c.722dupA (p.Val242Glyfs(*)33) in PEX5 (GenBank: NM_001131023.1). PEX5
      encodes two isoforms, PEX5L and PEX5S, and we show that the c.722dupA mutation,
      located in the PEX5L-specific exon 9, results in loss of PEX5L only. Both PEX5
      isoforms recognize PTS1-tagged proteins, but PEX5L is also a co-receptor for PTS2
      tagged proteins. Previous patients with PEX5 mutations had ZSD, mainly due to
      deficient import of PTS1-tagged proteins. Similarly to mutations in PEX7, loss of
      PEX5L results in deficient import of PTS2-tagged proteins only, thus causing RCDP
      instead of ZSD. We demonstrate that PEX5L expression restores the import of PTS2
      tagged proteins in patient fibroblasts. Due to the biochemical overlap between
      RCDP1 and RCDP5, sequencing of PEX7 and exon 9 in PEX5 should be performed in
      patients with a selective defect in the import of PTS2-tagged proteins. 

PMID- 26220974
TI  - Activating the translational repressor 4E-BP or reducing S6K-GSK3beta activity
      prevents accelerated axon growth induced by hyperactive mTOR in vivo.
AB  - Abnormal axonal connectivity and hyperactive mTOR complex 1 (mTORC1) are shared
      features of several neurological disorders. Hyperactive mTORC1 alters axon length
      and polarity of hippocampal neurons in vitro, but the impact of hyperactive
      mTORC1 on axon growth in vivo and the mechanisms underlying those effects remain
      unclear. Using in utero electroporation during corticogenesis, we show that
      increasing mTORC1 activity accelerates axon growth without multiple axon
      formation. This was prevented by counteracting mTORC1 signaling through p70S6Ks
      (S6K1/2) or eukaryotic initiation factor 4E-binding protein (4E-BP1/2), which
      both regulate translation. In addition to regulating translational targets, S6K1
      indirectly signals through GSK3beta, a regulator of axogenesis. Although blocking
      GSK3beta activity did not alter axon growth under physiological conditions in
      vivo, blocking it using a dominant-negative mutant or lithium chloride prevented
      mTORC1-induced accelerated axon growth. These data reveal the contribution of
      translational and non-translational downstream effectors such as GSK3beta to
      abnormal axon growth in neurodevelopmental mTORopathies and open new therapeutic
      options for restoring long-range connectivity. 

PMID- 26220975
TI  - Layered genetic control of DNA methylation and gene expression: a locus of
      multiple sclerosis in healthy individuals.
AB  - DNA methylation may contribute to the etiology of complex genetic disorders
      through its impact on genome integrity and gene expression; it is modulated by
      DNA-sequence variants, named methylation quantitative trait loci (meQTLs). Most
      meQTLs influence methylation of a few CpG dinucleotides within short genomic
      regions (<3 kb). Here, we identified a layered genetic control of DNA methylation
      at numerous CpGs across a long 300 kb genomic region. This control involved a
      single long-range meQTL and multiple local meQTLs. The long-range meQTL explained
      up to 75% of variance in methylation of CpGs located over extended areas of the
      300 kb region. The meQTL was identified in four samples (P = 2.8 * 10(-17), 3.1 *
      10(-31), 4.0 * 10(-71) and 5.2 * 10(-199)), comprising a total of 2796
      individuals. The long-range meQTL was strongly associated not only with DNA
      methylation but also with mRNA expression of several genes within the 300 kb
      region (P = 7.1 * 10(-18)-1.0 * 10(-123)). The associations of the meQTL with
      gene expression became attenuated when adjusted for DNA methylation (causal
      inference test: P = 2.4 * 10(-13)-7.1 * 10(-20)), indicating coordinated
      regulation of DNA methylation and gene expression. Further, the long-range meQTL
      was found to be in linkage disequilibrium with the most replicated locus of
      multiple sclerosis, a disease affecting primarily the brain white matter. In
      middle-aged adults free of the disease, we observed that the risk allele was
      associated with subtle structural properties of the brain white matter found in
      multiple sclerosis (P = 0.02). In summary, we identified a long-range meQTL that
      controls methylation and expression of several genes and may be involved in
      increasing brain vulnerability to multiple sclerosis. 

PMID- 26220976
TI  - Engrailed-2 (En2) deletion produces multiple neurodevelopmental defects in
      monoamine systems, forebrain structures and neurogenesis and behavior.
AB  - Many genes involved in brain development have been associated with human
      neurodevelopmental disorders, but underlying pathophysiological mechanisms remain
      undefined. Human genetic and mouse behavioral analyses suggest that ENGRAILED-2
      (EN2) contributes to neurodevelopmental disorders, especially autism spectrum
      disorder. In mouse, En2 exhibits dynamic spatiotemporal expression in embryonic
      mid-hindbrain regions where monoamine neurons emerge. Considering their
      importance in neuropsychiatric disorders, we characterized monoamine systems in
      relation to forebrain neurogenesis in En2-knockout (En2-KO) mice. Transmitter
      levels of serotonin, dopamine and norepinephrine (NE) were dysregulated from
      Postnatal day 7 (P7) to P21 in En2-KO, though NE exhibited the greatest
      abnormalities. While NE levels were reduced ~35% in forebrain, they were
      increased 40 -: 75% in hindbrain and cerebellum, and these patterns paralleled
      changes in locus coeruleus (LC) fiber innervation, respectively. Although En2
      promoter was active in Embryonic day 14.5 -: 15.5 LC neurons, expression
      diminished thereafter and gene deletion did not alter brainstem NE neuron
      numbers. Significantly, in parallel with reduced NE levels, En2-KO forebrain
      regions exhibited reduced growth, particularly hippocampus, where P21 dentate
      gyrus granule neurons were decreased 16%, suggesting abnormal neurogenesis.
      Indeed, hippocampal neurogenic regions showed increased cell death (+77%) and
      unexpectedly, increased proliferation. Excess proliferation was restricted to
      early Sox2/Tbr2 progenitors whereas increased apoptosis occurred in
      differentiating (Dcx) neuroblasts, accompanied by reduced newborn neuron
      survival. Abnormal neurogenesis may reflect NE deficits because intra-hippocampal
      injections of beta-adrenergic agonists reversed cell death. These studies suggest
      that disruption of hindbrain patterning genes can alter monoamine system
      development and thereby produce forebrain defects that are relevant to human
      neurodevelopmental disorders. 

PMID- 26220978
TI  - Altered TFEB-mediated lysosomal biogenesis in Gaucher disease iPSC-derived
      neuronal cells.
AB  - Gaucher disease (GD) is caused by mutations in the GBA1 gene, which encodes the
      lysosomal enzyme glucocerebrosidase (GCase). The severe forms of GD are
      associated with neurodegeneration with either rapid (Type 2) or slow progression
      (Type 3). Although the neurodegenerative process in GD has been linked to
      lysosomal dysfunction, the mechanisms involved are largely unknown. To identify
      the lysosomal alterations in GD neurons and uncover the mechanisms involved, we
      used induced pluripotent stem cells (iPSCs) derived from patients with GD. In GD
      iPSC-derived neuronal cells (iPSC-NCs), GBA1 mutations caused widespread
      lysosomal depletion, and a block in autophagic flux due to defective lysosomal
      clearance of autophagosomes. Autophagy induction by rapamycin treatment in GD
      iPSC-NCs led to cell death. Further analysis showed that in GD iPSC-NCs,
      expression of the transcription factor EB (TFEB), the master regulator of
      lysosomal genes, and lysosomal gene expression, were significantly downregulated.
      There was also reduced stability of the TFEB protein and altered lysosomal
      protein biosynthesis. Treatment of mutant iPSC-NCs with recombinant GCase
      (rGCase) reverted the lysosomal depletion and autophagy block. The effect of
      rGCase on restoring lysosomal numbers in mutant cells was enhanced in the
      presence of overexpressed TFEB, but TFEB overexpression alone did not reverse the
      lysosomal depletion phenotype. Our results suggest that GBA1 mutations interfere
      with TFEB-mediated lysosomal biogenesis, and that the action of GCase in
      maintaining a functioning pool of lysosomes is exerted in part through TFEB. The
      lysosomal alterations described here are likely to be a major determinant in GBA1
      associated neurodegeneration. 

PMID- 26220979
TI  - Neuropeptide Y mitigates neuropathology and motor deficits in mouse models of
      Machado-Joseph disease.
AB  - Machado-Joseph disease (MJD) is a fatal, dominantly inherited neurodegenerative
      disorder associated with an expanded polyglutamine tract within the ataxin-3
      protein, and characterized by progressive impairment of motor coordination,
      associated with neurodegeneration of specific brain regions, including cerebellum
      and striatum. The currently available therapies do not allow modification of
      disease progression. Neuropeptide Y (NPY) has been shown to exert potent
      neuroprotective effects by multiple pathways associated with the MJD mechanisms
      of disease. Thus, we evaluated NPY levels in MJD and investigated whether raising
      NPY by gene transfer would alleviate neuropathological and behavioural deficits
      in cerebellar and striatal mouse models of the disease. For that, a cerebellar
      transgenic and a striatal lentiviral-based models of MJD were used. NPY
      overexpression in the affected brain regions in these two mouse models was
      obtained by stereotaxic injection of adeno-associated viral vectors encoding NPY.
      Up to 8 weeks after viral injection, balance and motor coordination behaviour and
      neuropathology were analysed. We observed that NPY levels were decreased in two
      MJD patients' cerebella and in striata and cerebella of disease mouse models.
      Furthermore, overexpression of NPY alleviated the motor coordination impairments
      and attenuated the related neuropathological parameters, preserving cerebellar
      volume and granular layer thickness, reducing striatal lesion and decreasing
      mutant ataxin-3 aggregation. Additionally, NPY mediated increase of brain-derived
      neurotrophic factor levels and decreased neuroinflammation markers. Our data
      suggest that NPY is a potential therapeutic strategy for MJD. 

PMID- 26220977
TI  - A multiancestry study identifies novel genetic associations with CHRNA5
      methylation in human brain and risk of nicotine dependence.
AB  - Nicotine dependence is influenced by chromosome 15q25.1 single nucleotide
      polymorphisms (SNPs), including the missense SNP rs16969968 that alters function
      of the alpha5 nicotinic acetylcholine receptor (CHRNA5) and noncoding SNPs that
      regulate CHRNA5 mRNA expression. We tested for cis-methylation quantitative trait
      loci (cis-meQTLs) using SNP genotypes and DNA methylation levels measured across
      the IREB2-HYKK-PSMA4-CHRNA5-CHRNA3-CHRNB4 genes on chromosome 15q25.1 in the
      BrainCloud and Brain QTL cohorts [total N = 175 European-Americans and 65 African
      Americans (AAs)]. We identified eight SNPs that were significantly associated
      with CHRNA5 methylation in prefrontal cortex: P ranging from 6.0 * 10(-10) to 5.6
      * 10(-5). These SNP-methylation associations were also significant in frontal
      cortex, temporal cortex and pons: P ranging from 4.8 * 10(-12) to 3.4 * 10(-3).
      Of the eight cis-meQTL SNPs, only the intronic CHRNB4 SNP rs11636753 was
      associated with CHRNA5 methylation independently of the known SNP effects in
      prefrontal cortex, and it was the most significantly associated SNP with nicotine
      dependence across five independent cohorts (total N = 7858 European ancestry and
      3238 AA participants): P = 6.7 * 10(-4), odds ratio (OR) [95% confidence interval
      (CI)] = 1.11 (1.05-1.18). The rs11636753 major allele (G) was associated with
      lower CHRNA5 DNA methylation, lower CHRNA5 mRNA expression and increased nicotine
      dependence risk. Haplotype analyses showed that rs11636753-G and the functional
      rs16969968-A alleles together increased risk of nicotine dependence more than
      each variant alone: P = 3.1 * 10(-12), OR (95% CI) = 1.32 (1.22-1.43). Our
      findings identify a novel regulatory SNP association with nicotine dependence and
      connect, for the first time, previously observed differences in CHRNA5 mRNA
      expression and nicotine dependence risk to underlying DNA methylation
      differences. 

PMID- 26220980
TI  - Human SERPINB12 Is an Abundant Intracellular Serpin Expressed in Most Surface and
      Glandular Epithelia.
AB  - The intracellular serine protease inhibitors (serpins) are an important family of
      proteins that protect cells form proteinase-mediated injury. Understanding the
      tissue and cellular expression pattern of this protein family can provide
      important insights into their physiologic roles. For example, high expression in
      epithelial tissues, such as lung, may suggest a biologic function in cellular
      defense, secretion, or selective absorption. Although the expression pattern of
      many of the intracellular serpins has been well described, one member of this
      class, SERPINB12, has not been carefully examined. We generated a mouse
      monoclonal antibody directed against human SERPINB12 and delineated its
      specificity and tissue and cell type distribution pattern through immunoblotting
      and immunohistochemistry, respectively. This monoclonal antibody was human
      specific and did not cross-react with other human intracellular serpins or mouse
      Serpinb12. SERPINB12 was found in nearly all the tissues investigated. In
      addition, this serpin was found in multiple cell types within individual tissues
      but primarily the epithelium. These data suggest that SERPINB12, like some other
      intracellular serpins, may play a vital role in barrier function by providing
      protection of epithelial cells.

PMID- 26220981
TI  - Onyx extrusion through the scalp after embolization of dural arteriovenous
      fistula.
AB  - A man in his sixties referred with symptoms of episodic left lip numbness and
      left arm weakness was diagnosed with a Borden type 3 dural arteriovenous fistula
      (DAVF) on DSA. Successful Onyx embolization of the DAVF was performed via the
      distal left occipital artery using an ev3 Apollo detachable tip microcatheter. He
      underwent surgical obliteration for the residual DAVF 3 days later. Three months
      later during a routine postoperative clinic visit, the patient produced a plastic
      bag containing multiple small pieces of Onyx cast and the detached tip of the
      Apollo microcatheter that had extruded out from his scalp through small
      spontaneous holes about 5 weeks after the embolization procedure. This
      spontaneous extrusion of Onyx can be alarming to the patient not expecting it;
      however, prior knowledge and discussion can lessen the anxiety of both the
      treating physician and the patient dealing with such a situation.

PMID- 26220982
TI  - Pulmonary infiltrate and painful nodular leg lesions in a patient with membranous
      glomerulonephritis.
AB  - Nocardia otitidis-cavarium is rarely isolated as an infectious pathogen in the
      western world. We report on a 71-year-old Caucasian man with membranous
      glomerulonephritis who presented with several seemingly unrelated clinical
      symptoms that, after laborious diagnostics, turned out to be caused by
      disseminated infection with N. otitidis-cavarium. This case highlights the
      variable clinical presentations that can occur in nocardial infections and
      underscores the need to search for rare pathogens in patients taking
      immunosuppressive medication. 

PMID- 26220983
TI  - Chikungunya fever presenting with acute optic neuropathy.
AB  - Chikungunya fever is a vector borne virus that typically causes a self-limiting
      systemic illness with fever, skin rash and joint aches 2 weeks after infection.
      We present the case of a 69-year-old woman presenting with an acute unilateral
      optic neuropathy as a delayed complication of Chikungunya virus (CHIKV) infection
      contracted during a recent trip to the West Indies. She presented to our
      ophthalmology department with acute painless visual field loss in the right eye
      and a recent flu-like illness. She was found to have a right relative afferent
      pupillary defect (RAPD) with unilateral optic disc swelling. Serology confirmed
      recent CHIKV infection. Treatment with intravenous methylprednisolone was delayed
      while awaiting MRI scans and serology results. At 5-month follow-up, there was a
      persistent right RAPD and marked optic atrophy with a corresponding inferior
      scotoma in the visual field.

PMID- 26220984
TI  - Systemic and venous thromboembolism: think about paradoxical embolism.
AB  - Patent foramen ovale (PFO) is one of the most important causes of paradoxical
      embolism; it is found in about 25-30% of the population. In most patients, it is
      asymptomatic and diagnosis is usually made during routine echocardiography. In a
      small proportion of patients, PFO is diagnosed after paradoxical embolism is
      suspected. We present a case of a middle-aged smoker who was admitted with lower
      limb deep vein thrombosis and pulmonary embolism, who developed acute upper limb
      ischaemia during his inpatient stay. Since doctors might dismiss such cases as
      routine, this report highlights the importance of detailed history taking and
      examination in patients with venous thromboembolism. Paradoxical embolism should
      always be considered as a possible diagnosis when managing patients with
      concomitant venous and arterial embolism.

PMID- 26220985
TI  - Synthetic cannabinoids as a cause for black carbonaceous bronchoalveolar lavage.

PMID- 26220986
TI  - A drawing pin, drill bit, several staples and a magnet: definitely not a simple
      case of appendicitis.
AB  - The sequalae of foreign body ingestion may present in a number of manners and are
      even more prone to difficulties when a history of foreign body ingestion is not
      apparent. An 8-year-old boy with a short history of abdominal pain and vomiting
      presented to the hospital after seeing his general practitioner. He had a history
      of developmental delay. Examination revealed lower abdominal peritonism and his
      blood tests revealed elevated inflammatory markers. The patient was initially
      diagnosed with acute appendicitis and proceeded to theatre. At operation, the
      patient had a normal appendix but two perforations of the small bowel were
      incidentally discovered. After theatre, the patient underwent an abdominal X-ray,
      which revealed a number of radiopaque objects in the rectum. He returned to
      theatre where a number of metallic objects and a magnet were manually retrieved
      from the patient's rectum. He made a full recovery and was discharged home a few
      days later. 

PMID- 26220987
TI  - Right heart thrombus causing syncope in an elderly patient.
AB  - Pulmonary embolism and thromboembolic disease carry a high mortality if not
      recognised and managed appropriately. Herein we illustrate the case of a
      dehydrated elderly female patient with recurrent syncope who proved to have high
      risk pulmonary embolism and a free floating right heart thrombus. The
      echocardiographic findings of right heart thrombus and possible thrombi 'in
      transit' within a low flow inferior vena cava, guided a life-saving treatment in
      this frail elderly patient. 

PMID- 26220988
TI  - Multimorbidity patterns are differentially associated with functional ability and
      decline in a longitudinal cohort of older women.
AB  - BACKGROUND: we aimed to identify multimorbidity patterns and relate these
      patterns to functional ability and decline. METHODS: we included 7,270
      participants of the older cohort of the Australian Longitudinal Study on Women's
      Health, who were surveyed every 3 years from 2002 to 2011. We used factor
      analysis to identify multimorbidity patterns from 31 self-reported chronic
      conditions among women aged 76-81 in 2002. We applied a linear increments model
      to account for attrition and related the multimorbidity patterns to functional
      ability and decline at subsequent surveys, as measured by activities of daily
      living (ADL) and instrumental activities of daily living (IADL). For each
      pattern, we determined mean ADL and IADL scores in the middle and highest third
      of factor score in comparison to a reference group. RESULTS: we identified three
      multimorbidity patterns, labelled musculoskeletal/somatic (MSO),
      neurological/mental health (NMH) and cardiovascular (CVD). High factor scores for
      NMH, MSO and CVD were associated with significantly higher mean ADL and IADL
      scores (poorer functional ability) in 2005 compared with the reference group of
      low factor scores for all three factors. The CVD pattern was associated with the
      greatest decline in ADL between 2005 and 2011, whereas the NMH pattern was
      associated with the greatest decline in IADL. CONCLUSIONS: distinct
      multimorbidity patterns were differentially associated with functional ability
      and decline. Given the paucity of studies on multimorbidity patterns, future
      studies should seek to assess the reproducibility of our findings in other
      populations and settings, and investigate the potential implications for improved
      prediction of functional decline.

PMID- 26220989
TI  - Prevalence of sarcopenia in patients attending outpatient geriatric clinics: the
      ELLI study.
AB  - OBJECTIVES: the aim of this study is to know the prevalence of sarcopenia in
      geriatric outpatient clinics using the EGWSOP (European Working Group on
      Sarcopenia in Older People) diagnostic criteria that include muscle mass, muscle
      strength and physical performance. METHODS: subjects over 69 years old, able to
      walk without help and who attended five geriatric outpatient clinics were
      recruited. Body composition was assessed using bioimpedance analysis (BIA), grip
      strength using a JAMAR dynamometer and physical performance by the 4 m gait
      speed. Sarcopenia was diagnosed using the EGWSOP criteria (gait speed <0.8 m/s;
      grip strength <30 kg in men or <20 kg in women, and muscle mass index (MMI) <8.31
      kg/m(2) in men or <6.68 kg/m(2) in women). RESULTS: two hundred and ninety-eight
      subjects were included (median age 83.2 years, 63.1% women). 19.1% had sarcopenia
      (12.7% men, 22.9% women); 20.1% had low muscle mass; 68.8% had low gait speed and
      81.2% low grip strength. Only 21.9% of the subjects with low grip strength and
      19.5% of those with low gait speed had sarcopenia. No correlations between muscle
      mass and either muscle strength or gait speed were detected. CONCLUSIONS:
      sarcopenia is present in one out of five subjects attending geriatric outpatient
      clinics.

PMID- 26220990
TI  - Clarifying and defending the endorsed life approach to surrogate decision-making.

PMID- 26220991
TI  - Swimming in an Unsteady World.
AB  - When animals swim in aquatic habitats, the water through which they move is
      usually flowing. Therefore, an important part of understanding the physics of how
      animals swim in nature is determining how they interact with the fluctuating
      turbulent water currents in their environment. We addressed this issue using
      microscopic larvae of invertebrates in "fouling communities" growing on docks and
      ships to ask how swimming affects the transport of larvae between moving water
      and surfaces from which they disperse and onto which they recruit. Field
      measurements of the motion of water over fouling communities were used to design
      realistic turbulent wavy flow in a laboratory wave-flume over early-stage fouling
      communities. Fine-scale measurements of rapidly-varying water-velocity fields
      were made using particle-image velocimetry, and of dye-concentration fields
      (analog for chemical cues from the substratum) were made using planar laser
      induced fluorescence. We used individual-based models of larvae that were
      swimming, passively sinking, passively rising, or were passive and neutrally
      buoyant to determine how their trajectories were affected by their motion through
      the water, rotation by local shear, and transport by ambient flow. Swimmers moved
      up and down in the turbulent flow more than did neutrally buoyant larvae.
      Although more of the passive sinkers landed on substrata below them, and more
      passive risers on surfaces above, swimming was the best strategy for landing on
      surfaces if their location was not predictable (as is true for fouling
      communities). When larvae moved within 5 mm of surfaces below them, passive
      sinkers and neutrally-buoyant larvae landed on the substratum, whereas many of
      the swimmers were carried away, suggesting that settling larvae should stop
      swimming as they near a surface. Swimming and passively-rising larvae were best
      at escaping from a surface below them, as precompetent larvae must do to disperse
      away. Velocities, vorticities, and odor-concentrations encountered by larvae
      fluctuated rapidly, with peaks much higher than mean values. Encounters with
      concentrations of odor or with vorticities above threshold increased as larvae
      neared the substratum. Although microscopic organisms swim slowly, their
      locomotory behavior can affect where they are transported by the movement of
      ambient water as well as the signals they encounter when they move within a few
      centimeters of surfaces. 

PMID- 26220992
TI  - Origins, genetic landscape, and emerging therapies of small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths, with small cell lung cancer
      (SCLC) representing the most aggressive subtype. Standard treatments have not
      changed in decades, and the 5-year survival rate has remained <7%. Genomic
      analyses have identified key driver mutations of SCLC that were subsequently
      validated in animal models of SCLC. To provide better treatment options, a deeper
      understanding of the cellular and molecular mechanisms underlying SCLC
      initiation, progression, metastasis, and acquisition of resistance is required.
      In this review, we describe the genetic landscape of SCLC, features of the cell
      of origin, and targeted therapeutic approaches. 

PMID- 26220994
TI  - The oncogenic BRD4-NUT chromatin regulator drives aberrant transcription within
      large topological domains.
AB  - NUT midline carcinoma (NMC), a subtype of squamous cell cancer, is one of the
      most aggressive human solid malignancies known. NMC is driven by the creation of
      a translocation oncoprotein, BRD4-NUT, which blocks differentiation and drives
      growth of NMC cells. BRD4-NUT forms distinctive nuclear foci in patient tumors,
      which we found correlate with ~100 unprecedented, hyperacetylated expanses of
      chromatin that reach up to 2 Mb in size. These "megadomains" appear to be the
      result of aberrant, feed-forward loops of acetylation and binding of acetylated
      histones that drive transcription of underlying DNA in NMC patient cells and
      naive cells induced to express BRD4-NUT. Megadomain locations are typically cell
      lineage-specific; however, the cMYC and TP63 regions are targeted in all NMCs
      tested and play functional roles in tumor growth. Megadomains appear to originate
      from select pre-existing enhancers that progressively broaden but are ultimately
      delimited by topologically associating domain (TAD) boundaries. Therefore, our
      findings establish a basis for understanding the powerful role played by large
      scale chromatin organization in normal and aberrant lineage-specific gene
      transcription. 

PMID- 26220995
TI  - Structure of human MDM2 complexed with RPL11 reveals the molecular basis of p53
      activation.
AB  - The central region of MDM2 is critical for p53 activation and tumor suppression.
      Upon ribosomal stress, this region is bound by ribosomal proteins, particularly
      ribosomal protein L11 (RPL11), leading to MDM2 inactivation and subsequent p53
      activation. Here, we solved the complex structure of human MDM2-RPL11 at 2.4 A.
      MDM2 extensively interacts with RPL11 through an acidic domain and two zinc
      fingers. Formation of the MDM2-RPL11 complex induces substantial conformational
      changes in both proteins. RPL11, unable to bind MDM2 mutants, fails to induce the
      activation of p53 in cells. MDM2 mimics 28S rRNA binding to RPL11. The C4 zinc
      finger determines RPL11 binding to MDM2 but not its homolog, MDMX. Our results
      highlight the essential role of the RPL11-MDM2 interaction in p53 activation and
      tumor suppression and provide a structural basis for potential new anti-tumor
      drug development. 

PMID- 26220996
TI  - CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new
      mechanism for absence epilepsy.
AB  - CaV3.2 T-type calcium channels, encoded by CACNA1H, are expressed throughout the
      brain, yet their general function remains unclear. We discovered that CaV3.2
      channels control NMDA-sensitive glutamatergic receptor (NMDA-R)-mediated
      transmission and subsequent NMDA-R-dependent plasticity of AMPA-R-mediated
      transmission at rat central synapses. Interestingly, functional CaV3.2 channels
      primarily incorporate into synapses, replace existing CaV3.2 channels, and can
      induce local calcium influx to control NMDA transmission strength in an activity
      dependent manner. Moreover, human childhood absence epilepsy (CAE)-linked
      hCaV3.2(C456S) mutant channels have a higher channel open probability, induce
      more calcium influx, and enhance glutamatergic transmission. Remarkably, cortical
      expression of hCaV3.2(C456S) channels in rats induces 2- to 4-Hz spike and wave
      discharges and absence-like epilepsy characteristic of CAE patients, which can be
      suppressed by AMPA-R and NMDA-R antagonists but not T-type calcium channel
      antagonists. These results reveal an unexpected role of CaV3.2 channels in
      regulating NMDA-R-mediated transmission and a novel epileptogenic mechanism for
      human CAE. 

PMID- 26220997
TI  - The host Integrator complex acts in transcription-independent maturation of
      herpesvirus microRNA 3' ends.
AB  - Herpesvirus saimiri (HVS) is an oncogenic gamma-herpesvirus that produces
      microRNAs (miRNAs) by cotranscription of precursor miRNA (pre-miRNA) hairpins
      immediately downstream from viral small nuclear RNAs (snRNA). The host cell
      Integrator complex, which recognizes the snRNA 3' end processing signal (3' box),
      generates the 5' ends of HVS pre-miRNA hairpins. Here, we identify a novel 3' box
      like sequence (miRNA 3' box) downstream from HVS pre-miRNAs that is essential for
      miRNA biogenesis. In vivo knockdown and rescue experiments confirmed that the 3'
      end processing of HVS pre-miRNAs also depends on Integrator activity. Interaction
      between Integrator and HVS primary miRNA (pri-miRNA) substrates that contain only
      the miRNA 3' box was confirmed by coimmunoprecipitation and an in situ proximity
      ligation assay (PLA) that we developed to localize specific transient RNA-protein
      interactions inside cells. Surprisingly, in contrast to snRNA 3' end processing,
      HVS pre-miRNA 3' end processing by Integrator can be uncoupled from
      transcription, enabling new approaches to study Integrator enzymology. 

PMID- 26220993
TI  - Fibroblast growth factor signaling in skeletal development and disease.
AB  - Fibroblast growth factor (FGF) signaling pathways are essential regulators of
      vertebrate skeletal development. FGF signaling regulates development of the limb
      bud and formation of the mesenchymal condensation and has key roles in regulating
      chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review
      updates our review on FGFs in skeletal development published in Genes &
      Development in 2002, examines progress made on understanding the functions of the
      FGF signaling pathway during critical stages of skeletogenesis, and explores the
      mechanisms by which mutations in FGF signaling molecules cause skeletal
      malformations in humans. Links between FGF signaling pathways and other
      interacting pathways that are critical for skeletal development and could be
      exploited to treat genetic diseases and repair bone are also explored. 

PMID- 26220998
TI  - The poly(A)-binding protein Nab2 functions in RNA polymerase III transcription.
AB  - RNA polymerase III (RNAPIII) synthesizes most small RNAs, the most prominent
      being tRNAs. Although the basic mechanism of RNAPIII transcription is well
      understood, recent evidence suggests that additional proteins play a role in
      RNAPIII transcription. Here, we discovered by a genome-wide approach that Nab2, a
      poly(A)-binding protein important for correct poly(A) tail length and nuclear
      mRNA export, is present at all RNAPIII transcribed genes. The occupancy of Nab2
      at RNAPIII transcribed genes is dependent on transcription. Using a novel
      temperature-sensitive allele of NAB2, nab2-34, we show that Nab2 is required for
      the occupancy of RNAPIII and TFIIIB at target genes. Furthermore, Nab2 interacts
      with RNAPIII, TFIIIB, and RNAPIII transcripts. Importantly, impairment of Nab2
      function causes an RNAPIII transcription defect in vivo and in vitro. Taken
      together, we establish Nab2, an important mRNA biogenesis factor, as a novel
      player required for RNAPIII transcription by stabilizing TFIIIB and RNAPIII at
      promoters. 

PMID- 26220999
TI  - Patient-reported outcome measures after total knee arthroplasty: a systematic
      review.
AB  - OBJECTIVES: A lack of connection between surgeons and patients in evaluating the
      outcome of total knee arthroplasty (TKA) has led to the search for the ideal
      patient-reported outcome measure (PROM) to evaluate these procedures. We
      hypothesised that the desired psychometric properties of the ideal outcome tool
      have not been uniformly addressed in studies describing TKA PROMS. METHODS: A
      systematic review was conducted investigating one or more facets of patient
      reported scores for measuring primary TKA outcome. Studies were analysed by study
      design, subject demographics, surgical technique, and follow-up adequacy, with
      the 'gold standard' of psychometric properties being systematic development,
      validity, reliability, and responsiveness. RESULTS: A total of 38 articles
      reported outcomes from 47 different PROMS to 85 541 subjects at 26.3 months
      (standard deviation 30.8) post-operatively. Of the 38, eight developed new
      scores, 20 evaluated existing scores, and ten were cross-cultural adaptation of
      existing scores. Only six of 38 surveyed studies acknowledged all 'gold standard'
      psychometric properties. The most commonly studied PROMS were the Oxford Knee
      Score, New Knee Society Score, Osteoarthritis Outcome Score, and Western Ontario
      and McMaster Universities Osteoarthritis Index. CONCLUSIONS: A single, validated,
      reliable, and responsive PROM addressing TKA patients' priorities has not yet
      been identified. Moreover, a clear definition of a successful procedure remains
      elusive. Cite this article: Bone Joint Res 2015;4:120-127.

PMID- 26221000
TI  - The Stressometer: A Simple, Valid, and Responsive Measure of Psychological Stress
      in Inflammatory Bowel Disease Patients.
AB  - BACKGROUND AND AIMS: Psychological stress is associated with inflammatory bowel
      disease [IBD], but the nature of this relationship is complex. At present, there
      is no simple tool to screen for stress in IBD clinical practice or assess stress
      repeatedly in longitudinal studies. Our aim was to design a single-question
      'stressometer' to rapidly measure stress and validate this in IBD patients.
      METHODS: In all, 304 IBD patients completed a single-question 'stressometer'.
      This was correlated with stress as measured by the Depression Anxiety Stress
      Scales [DASS-21], quality of life, and disease activity. Test-retest reliability
      was assessed in 31 patients who completed the stressometer and the DASS-21 on two
      occasions 4 weeks apart. RESULTS: Stressometer levels correlated with the DASS-21
      stress dimension in both Crohn's disease [CD] (Spearman's rank correlation
      coefficient [rs] 0.54; p < 0.001) and ulcerative colitis [UC] [rs 0.59; p <
      0.001]. Stressometer levels were less closely associated with depression and
      anxiety [rs range 0.36 to 0.49; all p-values < 0.001]. Stressometer scores
      correlated with all four Short Health Scale quality of life dimensions in both CD
      and UC [rs range 0.35 to 0.48; all p-values < 0.001] and with disease activity in
      Crohn's disease [rs 0.46; p < 0.001] and ulcerative colitis [rs 0.20; p = 0.02].
      Responsiveness was confirmed with a test-retest correlation of 0.43 [p = 0.02].
      CONCLUSIONS: The stressometer is a simple, valid, and responsive measure of
      psychological stress in IBD patients and may be a useful patient-reported outcome
      measure in future IBD clinical and research assessments.

PMID- 26221001
TI  - Cape Gooseberry [Physalis peruviana L.] Calyces Ameliorate TNBS Acid-induced
      Colitis in Rats.
AB  - BACKGROUND AND AIMS: Physalis peruviana [cape gooseberry] is highly appreciated
      for its commercial value. The Colombian ecotype is in great demand in the
      international market, particularly for the unique morphological characteristics
      of the calyx, which has extended use as a traditional herbal remedy in Colombia
      because of its anti-inflammatory properties. In this work, the anti-inflammatory
      activity of the total ethereal extract of Physalis peruviana calyces was
      evaluated in preventive and therapeutic protocols in a TNBS acid-induced colitis
      rat model. METHODS: Colitis was induced by intrarectal administration of TNBS. An
      evaluation of macroscopic and histopathological parameters in colonic tissue was
      performed, along with the determination of myeloperoxidase enzyme activity,
      cytokine levels and gene expression. Additionally, effects on nitric oxide
      release by lipopolysaccharide [LPS]-stimulated RAW264.7 macrophages and the
      scavenging activity of DPPH and ABTS free radicals were determined. RESULTS: The
      treatment with the Physalis peruviana extract produced a significant improvement
      in the colonic tissue at both macroscopic and histological levels. IL-1beta and
      TNF-alpha production was reduced by the extract in both experimental approaches.
      The groups treated with Physalis peruviana showed a tendency to MUC2 up
      regulation and down-regulation of COX-2, iNOS, NLRP3, IL-1beta, IL-6 and IL-10
      expression. Nitric oxide release in RAW264.7 macrophages was significantly
      inhibited. CONCLUSIONS: The Physalis peruviana extract showed intestinal anti
      inflammatory activity in the TNBS-induced colitis model, placing this species'
      calyx, a natural derivative, as a promising source of metabolites that could be
      used in treatment for inflammatory bowel disease.

PMID- 26221002
TI  - Six Cases of Lung Injury Following Anti-tumour Necrosis Factor Therapy for
      Inflammatory Bowel Disease.
AB  - BACKGROUND AND AIMS: Limited data are available regarding the pulmonary toxicity
      of anti-tumour necrosis factor (anti-TNF) therapy for inflammatory bowel disease
      (IBD). METHODS: We retrospectively searched the IBD registry of Asan Medical
      Center in order to identify patients with lung injury following anti-TNF therapy.
      RESULTS: Among 1002 patients who were treated using anti-TNF therapy, six cases
      (0.6%) of anti-TNF-induced lung injury (ATILI) were identified. ATILI was
      observed soon after the beginning of anti-TNF therapy (two to four doses of anti
      TNF). All of these patients experienced improvements in their respiratory
      symptoms and radiographic findings once the anti-TNF therapy was discontinued.
      One patient who suffered ATILI following adalimumab was switched to subsequent
      infliximab and was without recurrence of ATILI. CONCLUSION: Clinicians should be
      vigilant regarding the possibility of ATILI in IBD patients treated with anti-TNF
      agents.

PMID- 26221003
TI  - Dietary intake of inulin-type fructans in active and inactive Crohn's disease and
      healthy controls: a case-control study.
AB  - BACKGROUND AND AIMS: Prebiotic inulin-type fructans are widely consumed in the
      diet and may have contrasting effects in Crohn's disease by stimulating gut
      microbiota and/or by generating functional gastrointestinal symptoms. The aim of
      this study was to measure fructan and oligofructose intakes in patients with
      active and inactive Crohn's disease compared with healthy controls. METHODS:
      Patients with active Crohn's disease (n = 98), inactive Crohn's (n = 99) and
      healthy controls (n = 106) were recruited to a case-control study. Dietary intake
      of inulin-type fructans was measured using a specific food frequency
      questionnaire and was compared between the three groups and between patients with
      different disease phenotypes (Montreal classification). Associations between
      intakes and disease activity (Harvey-Bradshaw Index, HBI) were also undertaken.
      RESULTS: Patients with active Crohn's disease had lower fructan intakes (median
      2.9 g/d, interquartile range [IQR] 1.8) than those with inactive Crohn's (3.6
      g/d, 2.1, p = 0.036) or controls (3.9 g/d, 2.1, p = 0.003) and lower
      oligofructose intakes (2.8 g/d, 1.8) than those with inactive Crohn's (3.5 g/d,
      2.2, p = 0.048) or controls (3.8 g/d, 2.1, p = 0.003). There were no differences
      in intakes related to disease site or behaviour. There were negative correlations
      between HBI well-being score and fructan intake (rho = -0.154, p = 0.03) and
      oligofructose intake (rho = -0.156, p = 0.028) and for the HBI abdominal pain
      score and fructan (rho = -0.164, p = 0.021) and oligofructose intake (rho = 
      0.157, p = 0.027). CONCLUSIONS: Patients with active Crohn's disease consume
      lower quantities of fructans and oligofructose than their inactive counterparts
      and healthy controls. The impact of lower intakes of prebiotic fructans on gut
      microbiota is unknown and warrants further research.

PMID- 26221004
TI  - Intravenous Clomipramine for Treatment-Resistant Obsessive-Compulsive Disorder.
AB  - BACKGROUND: This open trial was conducted to evaluate the effectiveness of
      intravenous clomipramine (CMI) in refractory obsessive-compulsive disorder (OCD).
      METHODS: Thirty OCD poor responders to previous multiple trials of anti-obsessive
      medications were selected and admitted to the hospital. Severity of the illness
      and response to treatment were primarily assessed by the Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS). CMI was gradually administered intravenously for one
      week. All patients were thereafter switched to oral CMI with a maximum dose of
      225 mg/day. RESULTS: The Y-BOCS total score mean at admission was in the severe
      range (24-31), and dropped on discharge and follow-ups to the moderate range (16
      23). At discharge, 23 patients (76.7%) had a decrease in Y-BOCS >= 25% and were
      considered responders, while only 18 (60%) were still responders at 24 weeks. No
      relevant persistent side effects were reported. CONCLUSION: Intravenous
      clomipramine could be of benefit for severe OCD cases that have not adequately
      responded to several therapies, including oral clomipramine.

PMID- 26221005
TI  - Cholinesterase Inhibitors for Lewy Body Disorders: A Meta-Analysis.
AB  - BACKGROUND: We performed a meta-analysis of cholinesterase inhibitors for
      patients with Lewy body disorders, such as Parkinson's disease, Parkinson's
      disease dementia, and dementia with Lewy bodies. METHODS: The meta-analysis
      included only randomized controlled trials of cholinesterase inhibitors for Lewy
      body disorders. RESULTS: Seventeen studies (n = 1798) were assessed.
      Cholinesterase inhibitors significantly improved cognitive function (standardized
      mean difference [SMD] = -0.53], behavioral disturbances (SMD = -0.28), activities
      of daily living (SMD = -0.28), and global function (SMD = -0.52) compared with
      control treatments. Changes in motor function were not significantly different
      from control treatments. Furthermore, the cholinesterase inhibitor group had a
      higher all-cause discontinuation (risk ratio [RR] = 1.48, number needed to harm
      [NNH] = 14), discontinuation due to adverse events (RR = 1.59, NNH = 20), at
      least one adverse event (RR = 1.13, NNH = 11), nausea (RR = 2.50, NNH = 13), and
      tremor (RR = 2.30, NNH = 20). CONCLUSIONS: Cholinesterase inhibitors appear
      beneficial for the treatment of Lewy body disorders without detrimental effects
      on motor function. However, a careful monitoring of treatment compliance and side
      effects is required.

PMID- 26221006
TI  - News Feature: Microbes on the mind.

PMID- 26221008
TI  - Electric vehicle footprint analysis is misleading.

PMID- 26221009
TI  - Comparative study on the effectiveness of corticosteroid injections between
      trigger fingers with and without proximal interphalangeal joint flexion
      contracture.
AB  - Trigger fingers with proximal interphalangeal joint flexion contracture are
      suggested to have a poorer response to corticosteroid injection than those
      without contracture, though this has not been proven scientifically. We compared
      the clinical response to corticosteroid injection between trigger fingers with
      and without proximal interphalangeal joint contracture, and investigated the
      influence of the injection on the A1 pulley and flexor digitorum tendons using
      ultrasonography. One month after injection, pain was significantly reduced in the
      no contracture group, and 56% of trigger fingers with proximal interphalangeal
      joint contracture resolved. Before injection, relative thickening of the A1
      pulley and flexor digitorum tendons, and a partial hypoechoic lesion of the
      flexor digitorum superficialis tendon were observed in the contracture group. One
      month after injection, the thickening of the tendons and the A1 pulley was
      reduced, but the partial hypoechoic lesion was still observed in significant
      numbers. We have demonstrated that the presence of a proximal interphalangeal
      joint contracture was associated with a reduced clinical response to
      corticosteroid injection, and we suggest that the pathologic change in the flexor
      digitorum superficialis tendon, represented by the partial hypoechoic lesion,
      contributed to corticosteroid injection resistance. LEVEL OF EVIDENCE: IV.

PMID- 26221010
TI  - Prevalence, characteristics and natural history of cold intolerance after the
      reverse digital artery flap.
AB  - This retrospective study was designed to investigate the prevalence,
      characteristics and natural history of cold intolerance after the use of the
      reverse digital artery flap. A total of 123 patients were treated between 2010
      and 2013. After excluding patients who were lost to follow-up, 87 patients were
      studied. The mean follow-up time was 34 months (range 14-61). Cold intolerance
      occurred in 60% (52) of patients after the reverse digital artery flap procedure.
      The condition improved in only 15% (8) of the patients. Significant differences
      were observed in the age and the specific digit involved between the groups with
      and without cold intolerance. There was a lower incidence in younger patients,
      and the ring finger group showed a lower incidence than in other fingers.
      Furthermore, the Cold Intolerance Symptom Severity score was positively
      correlated with the temperature at which cold intolerance was triggered. LEVEL OF
      EVIDENCE: IV.

PMID- 26221011
TI  - Andreas Vesalius' 500th anniversary: the initiation of hand and forearm myology.
AB  - Andreas Vesalius (1515-1564) was the first to market an illustrated text on the
      freshly dissected muscular anatomy of the human hand and forearm when he
      published his De Fabrica Corporis Humani Libri Septem, in 1543. To commemorate
      his 500th birthday, we searched the second of seven books composing De Fabrica,
      the annotated woodcut illustrations of De Fabrica, the Tabulae Sex, and Epitome,
      and an eyewitness report of a public dissection by Vesalius for references to the
      morphology and functions of these muscles. We found Vesalius to have recognized
      all currently distinguished muscles except the palmaris brevis and he noted
      occasional absence of some muscles. Generally, he limited the origin and
      insertion to bones, largely disregarding attachments to membranes and fascia.
      Functionally, he recorded the muscles as having a single vector and operating on
      only one joint. We conclude that Vesalius was nearly completely correct about the
      anatomy of the muscles of the forearm, but much less accurate about their
      function. LEVEL OF EVIDENCE: 5.

PMID- 26221012
TI  - Treatment of a recurrent digital hyperkeratosis in a skin graft with a CO2 laser.

PMID- 26221013
TI  - Subclinical hypothyroidism: a 'laboratory-induced' condition?
AB  - OBJECTIVE: In current literature and guidelines, there is a tendency to define
      absolute TSH concentrations at which patient follow-up or even pharmaceutical
      intervention should be initiated. As TSH concentrations depend on the analytical
      method/platform used for TSH quantification, absolute cut-off values may pose
      threats for uniform clinical decision-making. In this study we therefore set out
      to clarify to what extent the method/platform and the reference values applied
      for TSH influence the clinical interpretation of thyroid parameters. DESIGN AND
      METHODS: We retrospectively analyzed anonymous TSH results from the Dutch
      external quality assessment program (EQAS) in relation to reference values
      advised by different manufacturers. We also examined TSH/free thyroxin (fT4)
      reference ranges and prevalence of thyroid pathology among different Dutch
      laboratories, including four cases in which a switch in the measuring platform
      was made. RESULTS: Our data show that interpretation of thyroid parameters is not
      only influenced by between-method/platform variation, but is also substantially
      affected by the variation in TSH/fT4 reference intervals applied in individual
      laboratories. Additionally, we show that the transition to a novel analytical
      method/platform can result in a shift in the prevalence of thyroid pathology,
      especially for subclinical hypothyroidism. CONCLUSIONS: Subclinical
      hypothyroidism can be a 'laboratory-induced' condition. This is an undesirable
      situation in regard to the clinical implications such a diagnosis can have for
      patients.

PMID- 26221014
TI  - Learn fast by using BJSM's multiple choice questions.

PMID- 26221016
TI  - Does running protect against knee osteoarthritis? Or promote it? Assessing the
      current evidence.

PMID- 26221015
TI  - Running shoes and running injuries: mythbusting and a proposal for two new
      paradigms: 'preferred movement path' and 'comfort filter'.
AB  - In the past 100 years, running shoes experienced dramatic changes. The question
      then arises whether or not running shoes (or sport shoes in general) influence
      the frequency of running injuries at all. This paper addresses five aspects
      related to running injuries and shoe selection, including (1) the changes in
      running injuries over the past 40 years, (2) the relationship between sport
      shoes, sport inserts and running injuries, (3) previously researched mechanisms
      of injury related to footwear and two new paradigms for injury prevention
      including (4) the 'preferred movement path' and (5) the 'comfort filter'.
      Specifically, the data regarding the relationship between impact characteristics
      and ankle pronation to the risk of developing a running-related injury is
      reviewed. Based on the lack of conclusive evidence for these two variables, which
      were once thought to be the prime predictors of running injuries, two new
      paradigms are suggested to elucidate the association between footwear and injury.
      These two paradigms, 'the preferred movement path' and 'the comfort filter',
      suggest that a runner intuitively selects a comfortable product using their own
      comfort filter that allows them to remain in the preferred movement path. This
      may automatically reduce the injury risk and may explain why there does not seem
      to be a secular trend in running injury rates.

PMID- 26221017
TI  - Surveillance for antimicrobial resistance in Australian isolates of Clostridium
      difficile, 2013-14.
AB  - OBJECTIVES: The objective of this study was to determine the activity of
      fidaxomicin and comparator antimicrobials against Clostridium difficile isolated
      from patients with C. difficile infection (CDI) in Australian hospitals and in
      the community. METHODS: One private and one public laboratory from five states in
      Australia submitted a total of 474 isolates/PCR-positive stool samples during
      three collection periods in August-September 2013 (n = 175), February-March 2014
      (n = 134) and August-September 2014 (n = 165). Isolate identification was
      confirmed by selective culture for C. difficile and a proportion of isolates from
      each state were characterized by PCR for toxin genes and PCR ribotyping. MICs of
      fidaxomicin and eight comparator antimicrobials were determined for all isolates
      using agar methodology. RESULTS: Site collection yielded 440 isolates of C.
      difficile and PCR revealed a heterogeneous strain population comprising 37
      different PCR ribotypes (RTs), 95% of which were positive for tcdA and tcdB
      (A+B+). The most common RTs were 014 (29.8%) and 002 (15.9%). Epidemic RT 027 was
      not identified; however, small numbers of virulent RTs 078 and 244 were found.
      Resistance to vancomycin, metronidazole and fidaxomicin was not detected and
      resistance to moxifloxacin was very low (3.4%). Fidaxomicin showed potent in
      vitro activity against all 440 isolates (MIC50/MIC90 0.03/0.12 mg/L) and was
      superior to metronidazole (MIC50/MIC90 0.25/0.5 mg/L) and vancomycin (MIC50/MIC90
      1/2 mg/L). CONCLUSIONS: These data confirm the potent in vitro activity of
      fidaxomicin against C. difficile. Moreover, this study provides an important
      baseline for ongoing long-term surveillance of antimicrobial resistance and
      prospective tracking of prominent and emerging strain types.

PMID- 26221018
TI  - Class-specific relative genetic contribution for key antiretroviral drugs.
AB  - OBJECTIVES: Antiretroviral pharmacokinetics is defined by numerous factors
      affecting absorption, distribution, metabolism and elimination. Biological
      processes underpinning drug distribution are only partially characterized and
      multiple genetic factors generate cumulative or antagonistic interactions, which
      complicates the implementation of pharmacogenetic markers. The aim of this study
      was to assess the degree to which heredity influences pharmacokinetics through
      the quantification of the relative genetic contribution (rGC) for key
      antiretrovirals. METHODS: A total of 407 patients receiving lopinavir/ritonavir,
      atazanavir/ritonavir, atazanavir, efavirenz, nevirapine, etravirine, maraviroc,
      tenofovir or raltegravir were included. Intra-patient variability (SDw) and inter
      patient (SDb) variability were measured in patients with plasma concentrations
      available from more than two visits. The rGC was calculated using the following
      equation: 1 - (1 / F) where F = SDb(2) / SDw(2). RESULTS: Mean (95% CI) rGC was
      calculated to be 0.81 (0.72-0.88) for efavirenz, 0.74 (0.61-0.84) for nevirapine,
      0.67 (0.49-0.78) for etravirine, 0.65 (0.41-0.79) for tenofovir, 0.59 (0.38-0.74)
      for atazanavir, 0.47 (0.27-0.60) for atazanavir/ritonavir, 0.36 (0.01-0.48) for
      maraviroc, 0.15 (0.01-0.44) for lopinavir/ritonavir and 0 (0-0.33) for
      raltegravir. CONCLUSIONS: The rank order for genetic contribution to variability
      in plasma concentrations for the study drugs was efavirenz > nevirapine >
      etravirine > tenofovir > atazanavir > atazanavir/ritonavir > maraviroc >
      lopinavir/ritonavir > raltegravir, indicating that class-specific differences
      exist. The rGC strategy represents a useful tool to rationalize future
      investigations as drugs with higher rGC scores may represent better candidates
      for pharmacogenetic-pharmacokinetic studies.

PMID- 26221019
TI  - Early insights into the potential of the Oxford Nanopore MinION for the detection
      of antimicrobial resistance genes.
AB  - OBJECTIVES: Genome sequencing will be increasingly used in the clinical setting
      to tailor antimicrobial prescribing and inform infection control outbreaks. A
      recent technological innovation that could reduce the delay between pathogen
      sampling and data generation is single molecule sequencing. An example of this
      technology, which is undergoing evaluation through an early access programme, is
      the Oxford Nanopore MinION. METHODS: We undertook a feasibility study on six
      clinically significant pathogens, comparing the MinION to the Illumina MiSeq and
      PacBio RSII platforms. Genomic DNA was prepared and sequenced using the MinION as
      instructed by the manufacturer, and Illumina MiSeq and PacBio sequencing was
      performed using established methods. RESULTS: An evaluation of the accuracy of
      the MinION based on sequencing of an MRSA isolate showed that error rates were
      higher in the MinION reads, but provided an even coverage across the entire
      genome length. The MinION detected all of the expected carbapenemases and ESBL
      genes in five Gram-negative isolates and the mecA gene in an MRSA isolate.
      CONCLUSIONS: The MinION can detect the presence of acquired resistance genes, but
      improvements in accuracy are needed so that antimicrobial resistance associated
      with mutations in chromosomal genes can be identified.

PMID- 26221020
TI  - Endothelial depletion of murine SRF/MRTF provokes intracerebral hemorrhagic
      stroke.
AB  - Intracerebral hemorrhagic stroke and vascular dementia are age- and hypertension
      associated manifestations of human cerebral small vessel disease (SVD). Cerebral
      microvessels are formed by endothelial cells (ECs), which are connected through
      tight junctions, adherens junctions, and stabilizing basement membrane
      structures. These endothelial connections ensure both vessel stability and blood
      brain barrier (BBB) functions, the latter enabling selective exchange of ions,
      bioactive molecules, and cells between the bloodstream and brain tissue.
      Srf(iECKO) mice, permitting conditional EC-specific depletion of the
      transcription factor Serum Response Factor (SRF), suffer from loss of BBB
      integrity and intracerebral hemorrhaging. Cerebral microbleeds and larger
      hemorrhages developed upon postnatal and adult depletion of either SRF or its
      cofactors Myocardin Related Transcription Factor (MRTF-A/-B), revealing essential
      requirements of ongoing SRF/MRTF activity for maintenance of cerebral small
      vessel integrity. In vivo magnetic resonance imaging allowed detection,
      localization, and time-resolved quantification of BBB permeability and hemorrhage
      formation in Srf(iECKO) brains. At the molecular level, direct and indirect
      SRF/MRTF target genes, encoding structural components of tight junctions
      (Claudins and ZO proteins), adherens junctions (VE-cadherin, alpha-Actinin), and
      the basement membrane (Collagen IV), were down-regulated upon SRF depletion.
      These results identify SRF and its MRTF cofactors as major transcriptional
      regulators of EC junctional stability, guaranteeing physiological functions of
      the cerebral microvasculature. We hypothesize that impairments in SRF/MRTF
      activity contribute to human SVD pathology. 

PMID- 26221021
TI  - Essential roles of methionine and S-adenosylmethionine in the autarkic lifestyle
      of Mycobacterium tuberculosis.
AB  - Multidrug resistance, strong side effects, and compliance problems in TB
      chemotherapy mandate new ways to kill Mycobacterium tuberculosis (Mtb). Here we
      show that deletion of the gene encoding homoserine transacetylase (metA)
      inactivates methionine and S-adenosylmethionine (SAM) biosynthesis in Mtb and
      renders this pathogen exquisitely sensitive to killing in immunocompetent or
      immunocompromised mice, leading to rapid clearance from host tissues. Mtb
      DeltametA is unable to proliferate in primary human macrophages, and in vitro
      starvation leads to extraordinarily rapid killing with no appearance of
      suppressor mutants. Cell death of Mtb DeltametA is faster than that of other
      auxotrophic mutants (i.e., tryptophan, pantothenate, leucine, biotin), suggesting
      a particularly potent mechanism of killing. Time-course metabolomics showed
      complete depletion of intracellular methionine and SAM. SAM depletion was
      consistent with a significant decrease in methylation at the DNA level (measured
      by single-molecule real-time sequencing) and with the induction of several
      essential methyltransferases involved in biotin and menaquinone biosynthesis,
      both of which are vital biological processes and validated targets of
      antimycobacterial drugs. Mtb DeltametA could be partially rescued by biotin
      supplementation, confirming a multitarget cell death mechanism. The work
      presented here uncovers a previously unidentified vulnerability of Mtb-the
      incapacity to scavenge intermediates of SAM and methionine biosynthesis from the
      host. This vulnerability unveils an entirely new drug target space with the
      promise of rapid killing of the tubercle bacillus by a new mechanism of action. 

PMID- 26221022
TI  - Phytoplankton-bacterial interactions mediate micronutrient colimitation at the
      coastal Antarctic sea ice edge.
AB  - Southern Ocean primary productivity plays a key role in global ocean
      biogeochemistry and climate. At the Southern Ocean sea ice edge in coastal
      McMurdo Sound, we observed simultaneous cobalamin and iron limitation of surface
      water phytoplankton communities in late Austral summer. Cobalamin is produced
      only by bacteria and archaea, suggesting phytoplankton-bacterial interactions
      must play a role in this limitation. To characterize these interactions and
      investigate the molecular basis of multiple nutrient limitation, we examined
      transitions in global gene expression over short time scales, induced by shifts
      in micronutrient availability. Diatoms, the dominant primary producers, exhibited
      transcriptional patterns indicative of co-occurring iron and cobalamin
      deprivation. The major contributor to cobalamin biosynthesis gene expression was
      a gammaproteobacterial population, Oceanospirillaceae ASP10-02a. This group also
      contributed significantly to metagenomic cobalamin biosynthesis gene abundance
      throughout Southern Ocean surface waters. Oceanospirillaceae ASP10-02a displayed
      elevated expression of organic matter acquisition and cell surface attachment
      related genes, consistent with a mutualistic relationship in which they are
      dependent on phytoplankton growth to fuel cobalamin production. Separate
      bacterial groups, including Methylophaga, appeared to rely on phytoplankton for
      carbon and energy sources, but displayed gene expression patterns consistent with
      iron and cobalamin deprivation. This suggests they also compete with
      phytoplankton and are important cobalamin consumers. Expression patterns of
      siderophore- related genes offer evidence for bacterial influences on iron
      availability as well. The nature and degree of this episodic colimitation appear
      to be mediated by a series of phytoplankton-bacterial interactions in both
      positive and negative feedback loops. 

PMID- 26221023
TI  - SOD1 aggregation in ALS mice shows simplistic test tube behavior.
AB  - A longstanding challenge in studies of neurodegenerative disease has been that
      the pathologic protein aggregates in live tissue are not amenable to structural
      and kinetic analysis by conventional methods. The situation is put in focus by
      the current progress in demarcating protein aggregation in vitro, exposing new
      mechanistic details that are now calling for quantitative in vivo comparison. In
      this study, we bridge this gap by presenting a direct comparison of the
      aggregation kinetics of the ALS-associated protein superoxide dismutase 1 (SOD1)
      in vitro and in transgenic mice. The results based on tissue sampling by
      quantitative antibody assays show that the SOD1 fibrillation kinetics in vitro
      mirror with remarkable accuracy the spinal cord aggregate buildup and disease
      progression in transgenic mice. This similarity between in vitro and in vivo data
      suggests that, despite the complexity of live tissue, SOD1 aggregation follows
      robust and simplistic rules, providing new mechanistic insights into the ALS
      pathology and organism-level manifestation of protein aggregation phenomena in
      general. 

PMID- 26221024
TI  - A non-canonical ESCRT pathway, including histidine domain phosphotyrosine
      phosphatase (HD-PTP), is used for down-regulation of virally ubiquitinated MHC
      class I.
AB  - The Kaposi's sarcoma-associated herpes virus (KSHV) K3 viral gene product
      effectively down-regulates cell surface MHC class I. K3 is an E3 ubiquitin ligase
      that promotes Lys(63)-linked polyubiquitination of MHC class I, providing the
      signal for clathrin-mediated endocytosis. Endocytosis is followed by sorting into
      the intralumenal vesicles (ILVs) of multivesicular bodies (MVBs) and eventual
      delivery to lysosomes. The sorting of MHC class I into MVBs requires many
      individual proteins of the four endosomal sorting complexes required for
      transport (ESCRTs). In HeLa cells expressing the KSHV K3 ubiquitin ligase, the
      effect of RNAi-mediated depletion of individual proteins of the ESCRT-0 and ESCRT
      I complexes and three ESCRT-III proteins showed that these are required to down
      regulate MHC class I. However, depletion of proteins of the ESCRT-II complex or
      of the ESCRT-III protein, VPS20 (vacuolar protein sorting 20)/CHMP6 (charged MVB
      protein 6), failed to prevent the loss of MHC class I from the cell surface.
      Depletion of histidine domain phosphotyrosine phosphatase (HD-PTP) resulted in an
      increase in the cell surface concentration of MHC class I in HeLa cells
      expressing the KSHV K3 ubiquitin ligase. Rescue experiments with wild-type (WT)
      and mutant HD-PTP supported the conclusion that HD-PTP acts as an alternative to
      ESCRT-II and VPS20/CHMP6 as a link between the ESCRT-I and those ESCRT-III
      protein(s) necessary for ILV formation. Thus, the down-regulation of cell surface
      MHC class I, polyubiquitinated by the KSHV K3 ubiquitin ligase, does not employ
      the canonical ESCRT pathway, but instead utilizes an alternative pathway in which
      HD-PTP replaces ESCRT-II and VPS20/CHMP6. 

PMID- 26221025
TI  - Dengue NS3, an RNAi suppressor, modulates the human miRNA pathways through its
      interacting partner.
AB  - RNAi acts as a host immune response against non-self molecules, including
      viruses. Viruses evolved to neutralize this response by expressing suppressor
      proteins. In the present study, we investigated dengue virus non structural
      protein 3 (dvNS3), for its RNAi-suppressor activity in human cell lines. Dengue
      virus (DV) NS3 reverts the GFP expression in GFP-silenced cell lines. Pull-down
      assays of dvNS3 revealed that it interacts with the host factor human heat shock
      cognate 70 (hHSC70). Down-regulation of hHSC70 resulted in accumulation of dengue
      viral genomic RNA. Also, the interaction of dvNS3 with hHSC70 perturbs the
      formation of RISC (RNA-induced silencing complex)-loading complex (RLC), by
      displacing TRBP (TAR RNA-binding protein) and possibly impairing the downstream
      activity of miRNAs. Interestingly, some of these miRNAs have earlier been
      reported to be down-regulated upon DV infection in Huh7 cells. Further studies on
      the miRNA-mRNA relationship along with mRNA profiling of samples overexpressing
      dvNS3 revealed up-regulation of TAZ (tafazzin) and SYNGR1 (synaptogyrin 1), known
      dengue viral host factors (DVHFs). Importantly, overexpression of dvNS3 in human
      embryonic kidney (HEK) 293T cells resulted in modulation of both mature and
      precursor miRNAs in human cell lines. Subsequent analysis suggested that dvNS3
      induced stage-specific down-regulation of miRNAs. Taken together, these results
      suggest that dvNS3 affects biogenesis and function of host miRNAs to regulate
      DVHFs for favouring DV replication. 

PMID- 26221026
TI  - Selectivity in subunit composition of Ena/VASP tetramers.
AB  - The members of the actin regulatory family of Ena/VASP proteins form stable
      tetramers. The vertebrate members of the Ena/VASP family, VASP, Mena and EVL,
      have many overlapping properties and expression patterns, but functional and
      regulatory differences between paralogues have been observed. The formation of
      mixed oligomers may serve a regulatory role to refine Ena/VASP activity. While it
      has been assumed that family members can form mixed oligomers, this possibility
      has not been investigated systematically. Using cells expressing controlled
      combinations of VASP, Mena and EVL, we evaluated the composition of Ena/VASP
      oligomers and found that VASP forms oligomers without apparent bias with itself,
      Mena or EVL. However, Mena and EVL showed only weak hetero-oligomerization,
      suggesting specificity in the association of Ena/VASP family members. Co
      expression of VASP increased the ability of Mena and EVL to form mixed oligomers.
      Additionally, we found that the tetramerization domain (TD) at the C-termini of
      Ena/VASP proteins conferred the observed selectivity. Finally, we demonstrate
      that replacement of the TD with a synthetic tetramerizing coiled coil sequence
      supports homo-oligomerization and normal VASP subcellular localization.

PMID- 26221027
TI  - Role of tryptophan residues of Erv1: Trp95 and Trp183 are important for its
      folding and oxidase function.
AB  - Erv1 is an FAD-dependent thiol oxidase of the ERV (essential for respiration and
      viability)/ALR (augmenter of liver regeneration) sub-family and an essential
      component of the mitochondrial import and assembly pathway. Erv1 contains six
      tryptophan residues, which are all located in the highly conserved C-terminal FAD
      binding domain. Though important structural roles were predicted for the
      invariable Trp(95), no experimental study has been reported. In the present
      study, we investigated the structural and functional roles of individual
      tryptophan residues of Erv1. Six single tryptophan-to-phenylalanine yeast mutant
      strains were generated and their effects on cell viability were tested at various
      temperatures. Then, the mutants were purified from Escherichia coli. Their
      effects on folding, FAD-binding and Erv1 activity were characterized. Our results
      showed that Erv1(W95F) has the strongest effect on the stability and function of
      Erv1 and followed by Erv1(W183F). Erv1(W95F) results in a decrease in the Tm of
      Erv1 by 23 degrees C, a significant loss of the oxidase activity and thus causing
      cell growth defects at both 30 degrees C and 37 degrees C. Erv1(W183F) induces
      changes in the oligomerization state of Erv1, along with a pronounced effect on
      the stability of Erv1 and its function at 37 degrees C, whereas the other mutants
      had no clear effect on the function of Erv1 including the highly conserved
      Trp(157) mutant. Finally, computational analysis indicates that Trp(95) plays a
      key role in stabilizing the isoalloxazine ring to interact with Cys(133). Taken
      together, the present study provided important insights into the molecular
      mechanism of how thiol oxidases use FAD in catalysing disulfide bond formation. 

PMID- 26221028
TI  - Augmented vagal heart rate modulation in active hypoestrogenic pre-menopausal
      women with functional hypothalamic amenorrhoea.
AB  - Compared with eumenorrhoeic women, exercise-trained women with functional
      hypothalamic amenorrhoea (ExFHA) exhibit low heart rates (HRs) and absent reflex
      renin-angiotensin-system activation and augmentation of their muscle sympathetic
      nerve response to orthostatic stress. To test the hypothesis that their autonomic
      HR modulation is altered concurrently, three age-matched (pooled mean, 24 +/- 1
      years; mean +/- S.E.M.) groups of women were studied: active with either FHA
      (ExFHA; n=11) or eumenorrhoeic cycles (ExOv; n=17) and sedentary with
      eumenorrhoeic cycles (SedOv; n=17). Blood pressure (BP), HR and HR variability
      (HRV) in the frequency domain were determined during both supine rest and graded
      lower body negative pressure (LBNP; -10, -20 and -40 mmHg). Very low (VLF), low
      (LF) and high (HF) frequency power spectra (ms(2)) were determined and, owing to
      skewness, log10-transformed. LF/HF ratio and total power (VLF + LF + HF) were
      calculated. At baseline, HR and systolic BP (SBP) were lower (P<0.05) and HF and
      total power were higher (P<0.05) in ExFHA than in eumenorrhoeic women. In all
      groups, LBNP decreased (P<0.05) SBP, HF and total power and increased (P<0.05) HR
      and LF/HF ratio. However, HF and total power remained higher (P<0.05) and HR, SBP
      and LF/HF ratio remained lower (P<0.05) in ExFHA than in eumenorrhoeic women, in
      whom measures did not differ (P>0.05). At each stage, HR correlated inversely
      (P<0.05) with HF. In conclusion, ExFHA women demonstrate augmented vagal yet
      unchanged sympathetic HR modulation, both at rest and during orthostatic stress.
      Although the role of oestrogen deficiency is unclear, these findings are in
      contrast with studies reporting decreased HRV in hypoestrogenic post-menopausal
      women.

PMID- 26221029
TI  - "Mr Smith's been our problem child today...": anticipatory management
      communication (AMC) in VA end-of-shift medicine and nursing handoffs.
AB  - BACKGROUND: Tools and procedures designed to improve end-of-shift handoffs
      through standardisation of processes and reliance on technology may miss
      contextually sensitive information about anticipated events that emerges during
      face-to-face handoff interactions. Such information, what we refer to as
      anticipatory management communication (AMC), is necessary to ensure timely and
      safe patient care, but has been little studied and understood. OBJECTIVE: To
      investigate AMC and the role it plays in nursing and medicine handoffs. RESEARCH
      DESIGN: Qualitative thematic analysis based on audio recordings of nurse-to
      nurse, medical resident-to-resident and surgical intern-to-intern handoffs.
      SUBJECTS: 27 nurse handoff dyads and 18 medical resident and surgical intern
      handoff dyads at one VA Medical Center. RESULTS: Heads-up information was the
      most frequent type of AMC across all handoff dyads (N=257; 108 resident and 149
      nursing). Indirect instructions AMC was used in a little over half the resident
      handoff dyads, but occurred in all nursing dyads (292 instances). Direct
      instructions AMC occurred in roughly equal proportion across all dyads but at a
      modest frequency (N=45; 28 resident and 17 nursing). Direct (if/then) contingency
      AMC occurred in resident handoffs more frequently than in nursing handoffs (N=32;
      30 resident and 2 nursing). CONCLUSIONS: The different frequencies for types of
      AMC likely reflect differences in how residents and nurses work and disparate
      professional cultures. But, verbal communication in both groups included
      important information unlikely to be captured in written handoff tools or the
      electronic medical record, underscoring the importance of direct communication to
      ensure safe handoffs.

PMID- 26221030
TI  - Structural Determinants for Substrate Binding and Catalysis in Triphosphate
      Tunnel Metalloenzymes.
AB  - Triphosphate tunnel metalloenzymes (TTMs) are present in all kingdoms of life and
      catalyze diverse enzymatic reactions such as mRNA capping, the cyclization of
      adenosine triphosphate, the hydrolysis of thiamine triphosphate, and the
      synthesis and breakdown of inorganic polyphosphates. TTMs have an unusual tunnel
      domain fold that harbors substrate- and metal co-factor binding sites. It is
      presently poorly understood how TTMs specifically sense different triphosphate
      containing substrates and how catalysis occurs in the tunnel center. Here we
      describe substrate-bound structures of inorganic polyphosphatases from
      Arabidopsis and Escherichia coli, which reveal an unorthodox yet conserved mode
      of triphosphate and metal co-factor binding. We identify two metal binding sites
      in these enzymes, with one co-factor involved in substrate coordination and the
      other in catalysis. Structural comparisons with a substrate- and product-bound
      mammalian thiamine triphosphatase and with previously reported structures of mRNA
      capping enzymes, adenylate cyclases, and polyphosphate polymerases suggest that
      directionality of substrate binding defines TTM catalytic activity. Our work
      provides insight into the evolution and functional diversification of an ancient
      enzyme family. 

PMID- 26221031
TI  - FANCD2-associated nuclease 1, but not exonuclease 1 or flap endonuclease 1, is
      able to unhook DNA interstrand cross-links in vitro.
AB  - Cisplatin and its derivatives, nitrogen mustards and mitomycin C, are used widely
      in cancer chemotherapy. Their efficacy is linked primarily to their ability to
      generate DNA interstrand cross-links (ICLs), which effectively block the
      progression of transcription and replication machineries. Release of this block,
      referred to as unhooking, has been postulated to require endonucleases that
      incise one strand of the duplex on either side of the ICL. Here we investigated
      how the 5' flap nucleases FANCD2-associated nuclease 1 (FAN1), exonuclease 1
      (EXO1), and flap endonuclease 1 (FEN1) process a substrate reminiscent of a
      replication fork arrested at an ICL. We now show that EXO1 and FEN1 cleaved the
      substrate at the boundary between the single-stranded 5' flap and the duplex,
      whereas FAN1 incised it three to four nucleotides in the double-stranded region.
      This affected the outcome of processing of a substrate containing a nitrogen
      mustard-like ICL two nucleotides in the duplex region because FAN1, unlike EXO1
      and FEN1, incised the substrate predominantly beyond the ICL and, therefore,
      failed to release the 5' flap. We also show that FAN1 was able to degrade a
      linear ICL substrate. This ability of FAN1 to traverse ICLs in DNA could help to
      elucidate its biological function, which is currently unknown. 

PMID- 26221033
TI  - Amyloid Oligomers and Mature Fibrils Prepared from an Innocuous Protein Cause
      Diverging Cellular Death Mechanisms.
AB  - Despite significant advances, the molecular identity of the cytotoxic species
      populated during in vivo amyloid formation crucial for the understanding of
      neurodegenerative disorders is yet to be revealed. In this study lysozyme
      prefibrillar oligomers and fibrils in both mature and sonicated states have been
      isolated through an optimized ultrafiltration/ultracentrifugation method and
      characterized with various optical spectroscopic techniques, atomic force
      microscopy, and transmission electron microscopy. We examined their level and
      mode of toxicity on rat pheochromocytoma (PC12) cells in both differentiated and
      undifferentiated states. We find that oligomers and fibrils display cytotoxic
      capabilities toward cultured cells in vitro, with oligomers producing elevated
      levels of cellular injury toward undifferentiated PC12 cells (PC12(undiff)).
      Furthermore, dual flow cytometry staining experiments demonstrate that the
      oligomers and mature fibrils induce divergent cellular death pathways (apoptosis
      and secondary necrosis, respectively) in these PC12 cells. We have also shown
      that oligomers but not sonicated mature fibrils inhibit hippocampal long term
      potentiation, a form of synaptic plasticity implicated in learning and memory, in
      vivo. We conclude that our in vitro and in vivo findings confer a level of
      resistance toward amyloid fibrils, and that the PC 12-based comparative
      cytotoxicity assay can provide insights into toxicity differences between
      differently aggregated protein species. 

PMID- 26221032
TI  - CUX2 protein functions as an accessory factor in the repair of oxidative DNA
      damage.
AB  - CUX1 and CUX2 proteins are characterized by the presence of three highly similar
      regions called Cut repeats 1, 2, and 3. Although CUX1 is ubiquitously expressed,
      CUX2 plays an important role in the specification of neuronal cells and continues
      to be expressed in postmitotic neurons. Cut repeats from the CUX1 protein were
      recently shown to stimulate 8-oxoguanine DNA glycosylase 1 (OGG1), an enzyme that
      removes oxidized purines from DNA and introduces a single strand break through
      its apurinic/apyrimidinic lyase activity to initiate base excision repair. Here,
      we investigated whether CUX2 plays a similar role in the repair of oxidative DNA
      damage. Cux2 knockdown in embryonic cortical neurons increased levels of
      oxidative DNA damage. In vitro, Cut repeats from CUX2 increased the binding of
      OGG1 to 7,8-dihydro-8-oxoguanine-containing DNA and stimulated both the
      glycosylase and apurinic/apyrimidinic lyase activities of OGG1. Genetic
      inactivation in mouse embryo fibroblasts or CUX2 knockdown in HCC38 cells delayed
      DNA repair and increased DNA damage. Conversely, ectopic expression of Cut
      repeats from CUX2 accelerated DNA repair and reduced levels of oxidative DNA
      damage. These results demonstrate that CUX2 functions as an accessory factor that
      stimulates the repair of oxidative DNA damage. Neurons produce a high level of
      reactive oxygen species because of their dependence on aerobic oxidation of
      glucose as their source of energy. Our results suggest that the persistent
      expression of CUX2 in postmitotic neurons contributes to the maintenance of
      genome integrity through its stimulation of oxidative DNA damage repair. 

PMID- 26221034
TI  - Identification and Characterization of CD300H, a New Member of the Human CD300
      Immunoreceptor Family.
AB  - Recruitment of circulating monocytes and neutrophils to infection sites is
      essential for host defense against infections. Here, we identified a previously
      unannotated gene that encodes an immunoglobulin-like receptor, designated CD300H,
      which is located in the CD300 gene cluster. CD300H has a short cytoplasmic tail
      and associates with the signaling adaptor proteins, DAP12 and DAP10. CD300H is
      expressed on CD16(+) monocytes and myeloid dendritic cells. Ligation of CD300H on
      CD16(+) monocytes and myeloid dendritic cells with anti-CD300H monoclonal
      antibody induced the production of neutrophil chemoattractants. Interestingly,
      CD300H expression varied among healthy subjects, who could be classified into two
      groups according to "positive" and "negative" expression. Genomic sequence
      analysis revealed a single-nucleotide substitution (rs905709 (G -> A)) at a
      splice donor site on intron 1 on either one or both alleles. The International
      HapMap Project database has demonstrated that homozygosity for the A allele of
      single nucleotide polymorphism (SNP) rs905709 ("negative" expression) is highly
      frequent in Han Chinese in Beijing, Japanese in Tokyo, and Europeans (A/A
      genotype frequencies 0.349, 0.167, and 0.138, respectively) but extremely rare in
      Sub-Saharan African populations. Together, these results suggest that CD300H may
      play an important role in innate immunity, at least in populations that carry the
      G/G or G/A genotype of CD300H.

PMID- 26221035
TI  - Mitochondrial Citrate Transporter-dependent Metabolic Signature in the 22q11.2
      Deletion Syndrome.
AB  - The congenital disorder 22q11.2 deletion syndrome (22qDS), characterized by a
      hemizygous deletion of 1.5-3 Mb on chromosome 22 at locus 11.2, is the most
      common microdeletion disorder (estimated prevalence of 1 in 4000) and the second
      risk factor for schizophrenia. Nine of ~30 genes involved in 22qDS have the
      potential of disrupting mitochondrial metabolism (COMT, UFD1L, DGCR8, MRPL40,
      PRODH, SLC25A1, TXNRD2, T10, and ZDHHC8). Deficits in bioenergetics during early
      postnatal brain development could set the basis for a disrupted neuronal
      metabolism or synaptic signaling, partly explaining the higher incidence in
      developmental and behavioral deficits in these individuals. Here, we investigated
      whether mitochondrial outcomes and metabolites from 22qDS children segregated
      with the altered dosage of one or several of these mitochondrial genes
      contributing to 22qDS etiology and/or morbidity. Plasma metabolomics, lymphocytic
      mitochondrial outcomes, and epigenetics (histone H3 Lys-4 trimethylation and 5
      methylcytosine) were evaluated in samples from 11 22qDS children and 13 age- and
      sex-matched neurotypically developing controls. Metabolite differences between
      22qDS children and controls reflected a shift from oxidative phosphorylation to
      glycolysis (higher lactate/pyruvate ratios) accompanied by an increase in
      reductive carboxylation of alpha-ketoglutarate (increased concentrations of 2
      hydroxyglutaric acid, cholesterol, and fatty acids). Altered metabolism in 22qDS
      reflected a critical role for the haploinsufficiency of the mitochondrial citrate
      transporter SLC25A1, further enhanced by HIF-1alpha, MYC, and metabolite
      controls. This comprehensive profiling served to clarify the biochemistry of this
      disease underlying its broad, complex phenotype. 

PMID- 26221036
TI  - Neurotoxins from snake venoms and alpha-conotoxin ImI inhibit functionally active
      ionotropic gamma-aminobutyric acid (GABA) receptors.
AB  - Ionotropic receptors of gamma-aminobutyric acid (GABAAR) regulate neuronal
      inhibition and are targeted by benzodiazepines and general anesthetics. We show
      that a fluorescent derivative of alpha-cobratoxin (alpha-Ctx), belonging to the
      family of three-finger toxins from snake venoms, specifically stained the
      alpha1beta3gamma2 receptor; and at 10 MUm alpha-Ctx completely blocked GABA
      induced currents in this receptor expressed in Xenopus oocytes (IC50 = 236 nm)
      and less potently inhibited alpha1beta2gamma2 ~ alpha2beta2gamma2 >
      alpha5beta2gamma2 > alpha2beta3gamma2 and alpha1beta3delta GABAARs. The
      alpha1beta3gamma2 receptor was also inhibited by some other three-finger toxins,
      long alpha-neurotoxin Ls III and nonconventional toxin WTX. alpha-Conotoxin ImI
      displayed inhibitory activity as well. Electrophysiology experiments showed mixed
      competitive and noncompetitive alpha-Ctx action. Fluorescent alpha-Ctx, however,
      could be displaced by muscimol indicating that most of the alpha-Ctx-binding
      sites overlap with the orthosteric sites at the beta/alpha subunit interface.
      Modeling and molecular dynamic studies indicated that alpha-Ctx or alpha
      bungarotoxin seem to interact with GABAAR in a way similar to their interaction
      with the acetylcholine-binding protein or the ligand-binding domain of nicotinic
      receptors. This was supported by mutagenesis studies and experiments with alpha
      conotoxin ImI and a chimeric Naja oxiana alpha-neurotoxin indicating that the
      major role in alpha-Ctx binding to GABAAR is played by the tip of its central
      loop II accommodating under loop C of the receptors. 

PMID- 26221037
TI  - Pli1(PIAS1) SUMO ligase protected by the nuclear pore-associated SUMO protease
      Ulp1SENP1/2.
AB  - Covalent modification of the proteome by SUMO is critical for genetic stability
      and cell growth. Equally crucial to these processes is the removal of SUMO from
      its targets by the Ulp1 (HuSENP1/2) family of SUMO proteases. Ulp1 activity is
      normally spatially restricted, because it is localized to the nuclear periphery
      via interactions with the nuclear pore. Delocalization of Ulp1 causes DNA damage
      and cell cycle defects, phenotypes thought to be caused by inappropriate
      desumoylation of nucleoplasmic targets that are normally spatially protected from
      Ulp1. Here, we define a novel consequence of Ulp1 deregulation, with a major
      impact on SUMO pathway function. In fission yeast lacking Nup132 (Sc/HuNUP133),
      Ulp1 is delocalized and can no longer antagonize sumoylation of the PIAS family
      SUMO E3 ligase, Pli1. Consequently, SUMO chain-modified Pli1 is targeted for
      proteasomal degradation by the concerted action of a SUMO-targeted ubiquitin
      ligase (STUbL) and Cdc48-Ufd1-Npl4. Pli1 degradation causes the profound SUMO
      pathway defects and associated centromere dysfunction in cells lacking Nup132.
      Thus, perhaps counterintuitively, Ulp1-mediated desumoylation can promote SUMO
      modification by stabilizing a SUMO E3 ligase. 

PMID- 26221038
TI  - Activin Regulates Self-renewal and Differentiation of Trophoblast Stem Cells by
      Down-regulating the X Chromosome Gene Bcor.
AB  - The development of a functional placenta is largely dependent upon proper
      proliferation and differentiation of trophoblast stem cells (TSCs). Activin
      signaling has long been regarded to play important roles during this process, but
      the exact mechanism is largely unknown. Here, we demonstrate that the X
      chromosome gene BCL-6 corepressor (Bcor) is a critical downstream effector of
      activin to fine-tune mouse TSC fate decision. Bcor was specifically down
      regulated by activin A in TSCs in a dose-dependent manner, and immediately up
      regulated upon TSC differentiation. Knockdown of Bcor partially compensated for
      the absence of activin A in maintaining the self-renewal of TSCs together with
      FGF4, while promoting syncytiotrophoblast differentiation in the absence of FGF4.
      Moreover, the impaired trophoblast giant cell and spongiotrophoblast
      differentiation upon Bcor knockdown also resembled the function of activin.
      Reporter analysis showed that BCOR inhibited the expression of the key
      trophoblast regulator genes Eomes and Cebpa by binding to their promoter regions.
      Our findings provide us with a better understanding of placental development and
      placenta-related diseases. 

PMID- 26221039
TI  - Histone deacetylase 10 regulates DNA mismatch repair and may involve the
      deacetylation of MutS homolog 2.
AB  - MutS homolog 2 (MSH2) is an essential DNA mismatch repair (MMR) protein. It
      interacts with MSH6 or MSH3 to form the MutSalpha or MutSbeta complex,
      respectively, which recognize base-base mispairs and insertions/deletions and
      initiate the repair process. Mutation or dysregulation of MSH2 causes genomic
      instability that can lead to cancer. MSH2 is acetylated at its C terminus, and
      histone deacetylase (HDAC6) deacetylates MSH2. However, whether other regions of
      MSH2 can be acetylated and whether other histone deacetylases (HDACs) and histone
      acetyltransferases (HATs) are involved in MSH2 deacetylation/acetylation is
      unknown. Here, we report that MSH2 can be acetylated at Lys-73 near the N
      terminus. Lys-73 is highly conserved across many species. Although several Class
      I and II HDACs interact with MSH2, HDAC10 is the major enzyme that deacetylates
      MSH2 at Lys-73. Histone acetyltransferase HBO1 might acetylate this residue.
      HDAC10 overexpression in HeLa cells stimulates cellular DNA MMR activity, whereas
      HDAC10 knockdown decreases DNA MMR activity. Thus, our study identifies an HDAC10
      mediated regulatory mechanism controlling the DNA mismatch repair function of
      MSH2. 

PMID- 26221040
TI  - The Selective Degradation of Synaptic Connexin 43 Protein by Hypoxia-induced
      Autophagy Impairs Natural Killer Cell-mediated Tumor Cell Killing.
AB  - Although natural killer (NK) cells play an important role in the control of
      melanoma, hypoxic stress in the tumor microenvironment may impair NK-mediated
      tumor cell killing by mechanisms that are not fully understood. In this study, we
      investigated the effect of hypoxia on the expression and channel activity of
      connexin 43 (Cx43) in melanoma cells and its impact on their susceptibility to NK
      cell-mediated lysis. Our results demonstrated that hypoxic stress increases Cx43
      expression in melanoma cells via hypoxia-inducible factor-1alpha (HIF-1alpha)
      transcriptional activity. Hypoxic cells displaying increased Cx43 expression were
      less susceptible to NK cell-mediated lysis compared with normoxic cells
      expressing a moderate level of Cx43. Conversely, when overexpressed in normoxic
      tumor cells, Cx43 improves their susceptibility to N cell-mediated killing. We
      show that the NK cell immune synapse formed with normoxic melanoma cells is more
      stable and contains a high level of gap-junctional Cx43 whereas that formed with
      hypoxic cells is less stable and contains a significant lower level of gap
      junctional Cx43. We provide evidence that the activation of autophagy in hypoxic
      melanoma cells selectively degrades gap-junctional Cx43, leading to the
      destabilization of the immune synapse and the impairment of NK cell-mediated
      killing. Inhibition of autophagy by genetic or pharmacological approaches as well
      as expression of the non-degradable form of Cx43 significantly restore its
      accumulation at the immune synapse and improves N cell-mediated lysis of hypoxic
      melanoma cells. This study provides the first evidence that the hypoxic
      microenvironment negatively affects the immune surveillance of tumors by NK cells
      through the modulation of Cx43-mediated intercellular communications. 

PMID- 26221042
TI  - Sister Mary Joseph nodule.

PMID- 26221041
TI  - Dynamic Arginine Methylation of Tumor Necrosis Factor (TNF) Receptor-associated
      Factor 6 Regulates Toll-like Receptor Signaling.
AB  - Arginine methylation is a common post-translational modification, but its role in
      regulating protein function is poorly understood. This study demonstrates that,
      TNF receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase involved in
      innate immune signaling, is regulated by reversible arginine methylation in a
      range of primary and cultured cells. Under basal conditions, TRAF6 is methylated
      by the methyltransferase PRMT1, and this inhibits its ubiquitin ligase activity,
      reducing activation of toll-like receptor signaling. In response to toll-like
      receptor ligands, TRAF6 is demethylated by the Jumonji domain protein JMJD6.
      Demethylation is required for maximal activation of NF-kappaB. Loss of JMJD6
      leads to reduced response, and loss of PRMT1 leads to basal pathway activation
      with subsequent desensitization to ligands. In human primary cells, variations in
      the PRMT1/JMJD6 ratio significantly correlate with TRAF6 methylation, basal
      activation of NF-kappaB, and magnitude of response to LPS. Reversible arginine
      methylation of TRAF6 by the opposing effects of PRMT1 and JMJD6 is, therefore, a
      novel mechanism for regulation of innate immune pathways. 

PMID- 26221043
TI  - Bilateral sutural cataract.

PMID- 26221044
TI  - Pulmonary Rehabilitation in COPD: Effect of 2 Aerobic Exercise Intensities on
      Subject-Centered Outcomes--A Randomized Controlled Trial.
AB  - BACKGROUND: Exercise training is an important component of pulmonary
      rehabilitation, but it remains questionable how training intensity affects
      patient-centered outcomes. The aim of this study was to compare the effects of 2
      aerobic training intensities on health-related quality of life (HRQOL), symptom
      control, and exercise tolerance in subjects with COPD. METHODS: Thirty-four
      subjects with mild to very severe COPD participated in an equivalence/non
      inferiority randomized controlled trial with a parallel group blinded to 60 or
      80% maximum work rate (W max) aerobic training intensity. The intervention was an
      out-patient pulmonary rehabilitation program conducted 3 times/week for 8 weeks.
      Outcomes were assessed with the St George Respiratory Questionnaire (primary
      outcome), Mahler's dyspnea index, London Chest Activity of Daily Living scale, 6
      min walk test, and constant-load and incremental exercise tests. RESULTS:
      Subjects were randomly allocated to aerobic training intensity of 60% W max
      (group 1, n = 17) or 80% W max (group 2, n = 17). Although there were significant
      improvements in all outcomes for both groups, there were no between-group
      differences in mean change in the St George Respiratory Questionnaire (P = .31,
      95% CI -12.0 to 3.9), Mahler's dyspnea index (P = .38), London Chest Activity of
      Daily Living scale (P = .92), 6-min walk test (P = .50, 95% CI 6.2-71.1),
      constant-load exercise test (P = .50), and incremental exercise test (P = .12).
      There was only one exercise-related adverse event of cardiac symptoms.
      CONCLUSIONS: Aerobic training intensity of at least 60% W max has a positive
      impact on COPD patient-centered outcomes, with no additional benefit of
      increasing intensity to 80% W max in HRQOL, symptom control, and exercise
      tolerance, challenging the present clinical attitude of rehabilitation
      professionals. (ClinicalTrials.gov registration NCT01944072.).

PMID- 26221045
TI  - Low Cognitive Ability in Subjects With Bronchiectasis.
AB  - BACKGROUND: Bronchiectasis may change cognitive function. The mechanism
      responsible for cognitive dysfunction in COPD may be neuronal damage caused by
      hypoxia. Cognitive function in patients with bronchiectasis is also likely to be
      affected by similar mechanisms. The goal of this study was to determine the
      frequency and determinants of low cognitive ability in subjects with stable
      bronchiectasis. METHODS: Thirty subjects with stable bronchiectasis and 25
      healthy volunteers underwent a cognitive ability assessment using the Wechsler
      Adult Intelligence Scale. Bronchiectasis was diagnosed by high-resolution
      computed tomography of the chest. Age, body mass index, the Hospital Anxiety and
      Depression Scale, and pulmonary function were assessed. Perceived intensity of
      dyspnea after exercise (after climbing 3 flights of stairs) was estimated using a
      modified Borg scale. RESULTS: Mean scores on the verbal and performance tests and
      full-scale IQ scores were significantly lower in subjects with bronchiectasis
      than in healthy volunteers. Low cognitive ability in subjects with bronchiectasis
      was associated with higher depression scores, lower oxygen saturation, and poor
      lung function after adjusting for potential confounders in multivariate analysis.
      Borg scores after exercise in subjects with bronchiectasis and low cognitive
      ability were higher than those in subjects with bronchiectasis and high cognitive
      ability, despite similar PaO2 and FEV1 in both groups. CONCLUSIONS: Low cognitive
      ability in subjects with bronchiectasis may be associated with reduced lung
      function, more serious hypoxemia, and higher depressive symptoms. Subjects with
      bronchiectasis and low cognitive ability feel more intense dyspnea than do those
      with high cognitive ability.

PMID- 26221046
TI  - Punch biopsy for fat tissue collection in amyloidosis: is it time to stop needle
      aspiration?

PMID- 26221047
TI  - Detection of RNA nucleoside modifications with the uridine-specific ribonuclease
      MC1 from Momordica charantia.
AB  - A codon-optimized recombinant ribonuclease, MC1 is characterized for its uridine
      specific cleavage ability to map nucleoside modifications in RNA. The published
      MC1 amino acid sequence, as noted in a previous study, was used as a template to
      construct a synthetic gene with a natural codon bias favoring expression in
      Escherichia coli. Following optimization of various expression conditions, the
      active recombinant ribonuclease was successfully purified as a C-terminal His-tag
      fusion protein from E. coli [Rosetta 2(DE3)] cells. The isolated protein was
      tested for its ribonuclease activity against oligoribonucleotides and
      commercially available E. coli tRNA(Tyr I). Analysis of MC1 digestion products by
      ion-pairing reverse phase liquid-chromatography coupled with mass spectrometry
      (IP-RP-LC-MS) revealed enzymatic cleavage of RNA at the 5'-termini of uridine and
      pseudouridine, but cleavage was absent if the uridine was chemically modified or
      preceded by a nucleoside with a bulky modification. Furthermore, the utility of
      this enzyme to generate complementary digestion products to other common
      endonucleases, such as RNase T1, which enables the unambiguous mapping of
      modified residues in RNA is demonstrated. 

PMID- 26221048
TI  - Is the Sense of Agency in Schizophrenia Influenced by Resting-State Variation in
      Self-Referential Regions of the Brain?
AB  - Schizophrenia is a disturbance of the self, of which the attribution of agency is
      a major component. In this article, we review current theories of the Sense of
      Agency, their relevance to schizophrenia, and propose a novel framework for
      future research. We explore some of the models of agency, in which both bottom-up
      and top-down processes are implicated in the genesis of agency. We further this
      line of inquiry by suggesting that ongoing neurological activity (the brain's
      resting state) in self-referential regions of the brain can provide a deeper
      level of influence beyond what the current models capture. Based on neuroimaging
      studies, we suggest that aberrant activity in regions such as the default mode
      network of individuals with schizophrenia can lead to a misattribution of
      internally/externally generated stimuli. This can result in symptoms such as
      thought insertion and delusions of control. Consequently, neuroimaging can
      contribute to a more comprehensive conceptualization and measurement of agency
      and potential treatment implications. 

PMID- 26221049
TI  - Dopamine D2/3 Receptor Occupancy Following Dose Reduction Is Predictable With
      Minimal Plasma Antipsychotic Concentrations: An Open-Label Clinical Trial.
AB  - BACKGROUND: Population pharmacokinetics can predict antipsychotic blood
      concentrations at a given time point prior to a dosage change. Those predicted
      blood concentrations could be used to estimate the corresponding dopamine D2/3
      receptors (D2/3R) occupancy by antipsychotics based on the tight relationship
      between blood and brain pharmacokinetics. However, this 2-step prediction has
      never been tested. METHODS: Two blood samples were collected at separate time
      points from 32 clinically stable outpatients with schizophrenia (Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition; mean +/- SD age: 60.1 +/-
      7.3 years) to measure plasma concentrations of olanzapine or risperidone at
      baseline. Then, subjects underwent a dose reduction of olanzapine or risperidone
      and completed a [(11)C]-raclopride positron emission tomography scan to measure
      D2/3R occupancy in the putamen. The plasma concentration at the time of the scan
      was predicted with the 2 samples based on population pharmacokinetic model, using
      NONMEM. D2/3R occupancy was then estimated by incorporating the predicted plasma
      concentration in a hyperbole saturation model. The predicted occupancy was
      compared to the observed value. RESULTS: The mean (95% CI) prediction errors for
      the prediction of D2/3R occupancy were -1.76% (-5.11 to 1.58) for olanzapine and
      0.64% (-6.18 to 7.46) for risperidone. The observed and predicted D2/3R occupancy
      levels were highly correlated (r = 0.67, P = .001 for olanzapine; r = 0.67, P =
      .02 for risperidone). CONCLUSIONS: D2/3R occupancy levels can be predicted from
      blood drug concentrations collected prior to dosage change. Although this 2-step
      model is subject to a small degree of error, it could be used to select oral
      doses aimed at achieving optimal D2/3R occupancy on an individual basis.

PMID- 26221051
TI  - Theta Burst Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations:
      Negative Findings From a Double-Blind-Randomized Trial.
AB  - BACKGROUND: Auditory verbal hallucinations (AVH) in schizophrenia are resistant
      to antipsychotic medication in approximately 25% of patients. Treatment with
      repetitive transcranial magnetic stimulation (rTMS) for refractory AVH has shown
      varying results. A stimulation protocol using continuous theta burst rTMS (TB
      rTMS) showed high efficacy in open label studies. We tested TB-rTMS as a
      treatment strategy for refractory AVH in a double-blind, placebo-controlled
      trial. METHODS: Seventy-one patients with AVH were randomly allocated to TB-rTMS
      or placebo treatment. They received 10 TB-rTMS or sham treatments over the left
      temporoparietal cortex in consecutive days. AVH severity was assessed at
      baseline, end of treatment and follow-up using the Psychotic Symptom Rating Scale
      (PSYRATS) and the Auditory Hallucinations Rating Scale (AHRS). Other
      schizophrenia-related symptoms were assessed with the Positive and Negative
      Syndrome Scale (PANSS). RESULTS: Seven patients dropped out before completing the
      study. In the remaining 64, AVH improved significantly after treatment in both
      groups as measured with both PSYRATS and AHRS. PANSS positive and general
      subscores also decreased, but the negative subscores did not. However,
      improvement did not differ significantly between the TB-rTMS and the placebo
      group on any outcome measure. CONCLUSIONS: Symptom reduction could be achieved in
      patients with medication-resistant hallucinations, even within 1 week time.
      However, as both groups showed similar improvement, effects were general (ie,
      placebo-effects) rather than specific to treatment with continuous TB-rTMS. Our
      findings highlight the importance of double-blind trials including a sham-control
      condition to assess efficacy of new treatments such as TMS.

PMID- 26221050
TI  - Interventions to Address Medical Conditions and Health-Risk Behaviors Among
      Persons With Serious Mental Illness: A Comprehensive Review.
AB  - People with serious mental illness (SMI) have mortality rates 2 to 3 times higher
      than the overall US population, largely due to cardiovascular disease. The
      prevalence of cardiovascular risk factors such as obesity and diabetes mellitus
      and other conditions, such as HIV/AIDS, is heightened in this group. Based on the
      recommendations of a National Institute of Mental Health stakeholder meeting, we
      conducted a comprehensive review examining the strength of the evidence
      surrounding interventions to address major medical conditions and health-risk
      behaviors among persons with SMI. Peer-reviewed studies were identified using 4
      major research databases. Randomized controlled trials and observational studies
      testing interventions to address medical conditions and risk behaviors among
      persons with schizophrenia and bipolar disorder between January 2000 and June
      2014 were included. Information was abstracted from each study by 2 trained
      reviewers, who also rated study quality using a standard tool. Following
      individual study review, the quality of the evidence (high, medium, low) and the
      effectiveness of various interventions were synthesized. 108 studies were
      included. The majority of studies examined interventions to address
      overweight/obesity (n = 80). The strength of the evidence was high for 4
      interventions: metformin and behavioral interventions had beneficial effects on
      weight loss; and bupropion and varenicline reduced tobacco smoking. The strength
      of the evidence was low for most other interventions reviewed. Future studies
      should test long-term interventions to cardiovascular risk factors and health
      risk behaviors. In addition, future research should study implementation
      strategies to effectively translate efficacious interventions into real-world
      settings. 

PMID- 26221052
TI  - Multiple types of calcium channels arising from alternative translation
      initiation of the Orai1 message.
AB  - In mammals exclusively, the pore-forming Ca(2+) release-activated Ca(2+) (CRAC)
      channel subunit Orai1 occurs in two forms because of alternative translation
      initiation. The longer, mammal-specific Orai1alpha contains an additional 63
      amino acids upstream of the conserved start site for Orai1beta, which occurs at
      methionine 64 in Orai1alpha. Orai1 participates in the generation of three
      distinct Ca(2+) currents, including two store-operated currents: Icrac, which
      involves activation of Orai1 channels by the Ca(2+)-sensing protein STIM1
      (stromal interaction molecule 1), and Isoc, which involves an interaction among
      Orai1, the transient receptor potential (TRP) family member TRPC1 (TRP canonical
      1), and STIM1. Orai1 is also a pore-forming subunit of an arachidonic acid (or
      leukotriene C4)-regulated current Iarc that involves interactions among Orai1,
      Orai3, and STIM1. We evaluated the roles of the two Orai1 forms in the Ca(2+)
      currents Icrac, Isoc, and Iarc. We found that Orai1alpha and Orai1beta were
      largely interchangeable for Icrac and Isoc, although Orai1alpha exhibited
      stronger inhibition by Ca(2+). Only the mammalian-specific Orai1alpha functioned
      in the arachidonic acid-regulated current Iarc. Thus, alternative translation
      initiation of the Orai1 message produces at least three types of Ca(2+) channels
      with distinct signaling and regulatory properties. 

PMID- 26221053
TI  - NF-kappaB signaling relieves negative regulation by miR-194 in hepatocellular
      carcinoma by suppressing the transcription factor HNF-1alpha.
AB  - Constitutive activation of the proinflammatory transcription factor nuclear
      factor kappaB (NF-kappaB) plays an important role in progression of
      hepatocellular carcinoma (HCC). Emerging modulators of NF-kappaB signaling are
      noncoding RNAs, especially microRNAs (miRNAs). We previously identified miRNAs
      that reduced the induction of NF-kappaB activity upon addition of tumor necrosis
      factor-alpha (TNFalpha) to HCC cells. We found that among these miRNAs, the
      abundance of liver-enriched miR-194 was decreased in HCC tissue and that low
      abundance of miR-194 correlated with a high occurrence of vascular invasion.
      Overexpressing miR-194 suppressed HCC cell migration and invasiveness in culture
      and metastatic seeding in mice. Transcripts encoding tripartite motif containing
      23 (TRIM23), a ubiquitin ligase involved in NF-kappaB activation, and chromosome
      21 open reading frame 91 (C21ORF91), a protein of unknown function, were
      identified as direct targets of miR-194 in HCC cells; knocking down either
      protein decreased the activity of a luciferase NF-kappaB reporter. Furthermore,
      the NF-kappaB pathway activator TNFalpha, an inflammatory cytokine, inhibited the
      transcription of miR-194 by decreasing the abundance of hepatocyte nuclear factor
      1alpha (HNF-1alpha). The abundance of miR-194 positively correlated with that of
      HNF-1alpha and inversely correlated with that of TNFalpha in human HCC tissue.
      Thus, we identified a pathway in which TNFalpha-NF-kappaB signaling switches off
      negative regulation by suppressing HNF-1alpha-mediated expression of miR-194,
      revealing insight into the mechanisms linking inflammatory pathways, miRNA, and
      HCC metastasis. 

PMID- 26221054
TI  - Maintaining epithelial stemness with p63.
AB  - In stratified epithelial and glandular tissues, homeostasis relies on the self
      renewing capacity of stem cells, which are within the basal layer. The p53 family
      member p63 is an indispensable transcription factor for epithelial morphogenesis
      and stemness. A splice variant of the transcription factor p63 that lacks an
      amino-terminal domain, DeltaNp63, is selectively found in the basal compartments
      of several ectoderm-derived tissues such as stratified and glandular epithelia,
      in which it is required for the replenishment of stem cells. Thus far, the
      transcriptional programs downstream of p63 in stemness regulation remain
      incompletely defined. Unveiling the molecular basis of stem cell self-renewal may
      be relevant in understanding how this process may contribute to cancer
      development. In this review, we specifically highlight experimental
      investigations, which suggest that p63 is a marker of normal epithelial stem
      cells and describe p63 transcriptional targets that may be involved in stemness
      regulation. Finally, we discuss relevant findings implicating p63 in epithelial
      cancer stem cell biology. 

PMID- 26221055
TI  - Low dose CT of the lumbar spine compared with radiography: a study on image
      quality with implications for clinical practice.
AB  - BACKGROUND: Lumbar spine radiography is often performed instead of CT for
      radiation dose concerns. PURPOSE: To compare image quality and diagnostic
      information from low dose lumbar spine CT at an effective dose of about 1 mSv
      with lumbar spine radiography. MATERIAL AND METHODS: Fifty-one patients were
      examined by both methods. Five reviewers scored all examinations on eight image
      quality criteria using a five-graded scale and also assessed three common
      pathologic changes. RESULTS: Low dose CT scored better than radiography on the
      following: sharp reproduction of disc profile and vertebral end-plates (odds
      ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.5), intervertebral foramina
      and pedicles (OR, 4.3; 95% CI, 3.1-5.9), intervertebral joints (OR, 139; 95% CI,
      59-326), spinous and transverse processes (OR, 7.0; 95% CI, 4.3-11.2), sacro
      iliac joints (OR, 4.2; 95% CI, 3.2-5.7), reproduction of the adjacent soft
      tissues (OR, 2.9; 95% CI, 2.1-4.0), and absence of any obscuring superimposed
      gastrointestinal gas and contents (OR, 188; 95% CI, 66-539). Radiography scored
      better on sharp reproduction of cortical and trabecular bone (OR, 0.3; 95% CI,
      0.2-0.4). The reviewers visualized disk degeneration, spondylosis/diffuse
      idiopathic skeletal hyperostosis (DISH) and intervertebral joint osteoarthritis
      more clearly and were more certain with low dose CT. Mean time to review low dose
      CT was 204 s (95% CI, 194-214 s.), radiography 152 s (95% CI, 146-158 s.). The
      effective dose for low dose CT was 1.0-1.1 mSv, for radiography 0.7 mSv.
      CONCLUSION: Low dose lumbar spine CT at about 1 mSv has superior image quality to
      lumbar spine radiography with more anatomical and diagnostic information.

PMID- 26221056
TI  - Highly tunable perpendicularly magnetized synthetic antiferromagnets for
      biotechnology applications.
AB  - Magnetic micro and nanoparticles are increasingly used in biotechnological
      applications due to the ability to control their behavior through an externally
      applied field. We demonstrate the fabrication of particles made from ultrathin
      perpendicularly magnetized CoFeB/Pt layers with antiferromagnetic interlayer
      coupling. The particles are characterized by zero moment at remanence, low
      susceptibility at low fields, and a large saturated moment created by the
      stacking of the basic coupled bilayer motif. We demonstrate the transfer of
      magnetic properties from thin films to lithographically defined 2 MUm particles
      which have been lifted off into solution. We simulate the minimum energy state of
      a synthetic antiferromagnetic bilayer system that is free to rotate in an applied
      field and show that the low field susceptibility of the system is equal to the
      magnetic hard axis followed by a sharp switch to full magnetization as the field
      is increased. This agrees with the experimental results and explains the
      behaviour of the particles in solution.

PMID- 26221057
TI  - Mapping the magnetic and crystal structure in cobalt nanowires.
AB  - Using off-axis electron holography under Lorentz microscopy conditions to
      experimentally determine the magnetization distribution in individual cobalt (Co)
      nanowires, and scanning precession-electron diffraction to obtain their
      crystalline orientation phase map, allowed us to directly visualize with high
      accuracy the effect of crystallographic texture on the magnetization of
      nanowires. The influence of grain boundaries and disorientations on the magnetic
      structure is correlated on the basis of micromagnetic analysis in order to
      establish the detailed relationship between magnetic and crystalline structure.
      This approach demonstrates the applicability of the method employed and provides
      further understanding on the effect of crystalline structure on magnetic
      properties at the nanometric scale.

PMID- 26221058
TI  - Reducing risk, producing order: The surprisingly disciplinary world of needle
      exchange.
AB  - Emphasizing the reduction of risk over the cessation of drug use, needle exchange
      in the United States is often condemned for coddling its participants. Declining
      the punitive measures or unwavering teleology of criminal justice and drug
      treatment approaches, harm-reduction measures in general are faulted by naysayers
      for their refusal to establish clear normative boundaries for behavior
      modification. This article will seek to subvert such critiques by describing the
      ways in which disciplinary technologies suffused one needle exchange program in
      New York City. Drawing upon 1 year of participant observation at "Bronx Harm
      Reduction," this article will consider how the "minor procedures" of disciplinary
      power first characterized by Foucault (1977) worked to shape and organize
      different user bodies in needle exchange; it will further employ the work of
      Mitchell Dean to reflect upon the connections between program-level "technologies
      of agency" and government-led "technologies of performance." While conceding the
      overarching disciplinary transformation of late harm reduction, this article is
      specifically interested in the ramifications of this trajectory within one
      specific time and place. Namely, it postulates that attempts to "raise the bar"
      within a low-threshold program may serve to alienate or explicitly exclude
      certain service users.

PMID- 26221059
TI  - The Locus of Implicit Causality Effects in Comprehension.
AB  - Implicit causality might enable readers to focus on the imputed cause of an event
      and make it the default referent of a following pronoun. Alternatively, its
      effects might arise only when a following explicit cause is integrated with a
      description of the event. In three probe recognition experiments, in which the
      participants in the events were of the same sex, the only reliable effect - apart
      from the advantage of first mention - was that of whether implicit and explicit
      causes were the same. This effect was independent of whether the probe named the
      referent of the pronoun. In a fourth experiment, in which the two participants
      were of different sexes, there was no simple effect of implicit causality, but
      there was an advantage for the pronoun's referent. These results are consistent
      with the view that implicit causality has its effects at integration. We discuss
      their broader implications for theories of comprehension.

PMID- 26221060
TI  - Mental Fatigue and Executive Dysfunction in Patients with Cushing's Syndrome in
      Remission.
AB  - Patients with Cushing's syndrome (CS) in remission often suffer from impaired
      quality of life and cognitive dysfunction. The primary aim was to investigate the
      occurrence of mental fatigue, characterized by mental exhaustion and long
      recovery time following mentally strenuous tasks, in patients with CS in
      remission. The secondary aim was to examine whether the newly developed parts C
      and D of the trail making test (TMT) are more sensitive, compared to the
      conventional parts A and B, to evaluate attention and executive function. This
      was a cross-sectional study including 51 patients with CS in remission and 51
      controls. All subjects completed the self-administrated mental fatigue scale
      (MFS) and performed all four parts of the TMT. The patients had worse outcome on
      all components of the MFS except for sensitivity to noise. After adjustment for
      mental fatigue, depression, and anxiety, the patients performed worse only on
      part D of the TMT (P < 0.05). Mental fatigue is common in patients with CS in
      remission and can be captured by using the MFS. The most demanding part of the
      TMT, part D, is more useful to capture cognitive deficits in patients with CS in
      remission compared to the conventional parts A and B. 

PMID- 26221061
TI  - In Vivo and Impression Cytology Study on the Effect of Compatible Solutes Eye
      Drops on the Ocular Surface Epithelial Cell Quality in Dry Eye Patients.
AB  - The aim of this study is to investigate in vivo and ex vivo ocular surface
      alterations induced by dry eye disease and modification after osmoprotective
      therapy. Forty-eight eyes of 24 patients suffering from dry eye have been
      recruited. All patients received Optive (compatible solutes) eye drops in one
      randomly selected eye and Hylogel (sodium hyaluronate 0,2%) in the other. Follow
      up included a baseline visit and further examination 30-, 60-, and 90-day
      intervals (which comprises clinical evaluation, in vivo confocal microscopy-IVCM
      of the ocular surface, and conjunctival impression cytology). No significant
      difference in Schirmer I Test, TBUT, and vital staining results was observed
      during the follow-up period in both groups. IVCM showed in all patients an
      improvement of ocular surface epithelial morphology and signs of inflammation
      (oedema and keratocyte activation). However, these modifications were more
      evident in patients treated with Optive therapy. A significant reduction of the
      expression of MMP9 and IL6 in Optive group was observed during the follow-up
      period in comparison to Hylogel treatment. Our results show that in dry eye
      disease therapy based on osmoprotective eye drops determines a reduction of
      inflammatory activation of ocular surface, with consequent improvement of the
      quality of corneal and conjunctival epithelium. 

PMID- 26221062
TI  - Analysis of Th17 and Tc17 Frequencies and Antiviral Defenses in Gut-Associated
      Lymphoid Tissue of Chronic HIV-1 Positive Patients.
AB  - The complex relationship between both the Th1/Th17 and Tc1/Tc17 axis and innate
      defences in the intestinal mucosa during HIV-1 infection has not been well
      characterized. This study examined the frequency, phenotype, and functional
      status of T cell populations in the gut-associated lymphoid tissue and peripheral
      blood of virologically suppressed HIV-1-infected patients on therapy, focusing on
      the Th1, Th17, Tc1, and Tc17 cell subsets. We found a persistent immune cell
      activation (CD38 and HLADR expression) into the GALT despite the higher levels of
      Th17 and Tc17 in respect to peripheral blood. An upregulation of type I IFN
      response in GALT compared to the peripheral blood compartment was also recorded.
      Furthermore, IFN-alpha/beta levels were negatively related to the frequencies of
      Th1 naive cells and Tc1 cell subsets (naive, central memory, and effector memory)
      in the GALT. In contrast, no relationships between type I IFN response and Th1 or
      Tc1 cell subsets in peripheral blood compartment and between IFN-alpha/beta and
      Th17/Tc17 in both GALT and peripheral blood district were recorded. These data
      indicate that prolonged antiretroviral treatment improves GALT immune function
      despite the persistence of immune activation and type I IFN response in chronic
      HIV-1 positive patients. 

PMID- 26221064
TI  - Trimethyltin-Induced Microglial Activation via NADPH Oxidase and MAPKs Pathway in
      BV-2 Microglial Cells.
AB  - Trimethyltin (TMT) is known as a potent neurotoxicant that causes neuronal cell
      death and neuroinflammation, particularly in the hippocampus. Microglial
      activation is one of the prominent pathological features of TMT neurotoxicity.
      Nevertheless, it remains unclear how microglial activation occurs in TMT
      intoxication. In this study, we aimed to investigate the signaling pathways in
      TMT-induced microglial activation using BV-2 murine microglial cells. Our results
      revealed that TMT generates reactive oxygen species (ROS) and increases the
      expression of CD11b and nuclear factor-kappaB- (NF-kappaB-) mediated nitric oxide
      (NO) and tumor necrosis factor- (TNF-) alpha in BV-2 cells. We also observed that
      NF-kappaB activation was controlled by p38 and JNK phosphorylation. Moreover, TMT
      induced ROS generation occurred via nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase in BV-2 cells. Interestingly, treatment with the NADPH oxidase
      inhibitor apocynin significantly suppressed p38 and JNK phosphorylation and NF
      kappaB activation and ultimately the production of proinflammatory mediators upon
      TMT exposure. These findings indicate that NADPH oxidase-dependent ROS generation
      activated p38 and JNK mitogen-activated protein kinases (MAPKs), which then
      stimulated NF-kappaB to release proinflammatory mediators in the TMT-treated BV-2
      cells. 

PMID- 26221063
TI  - Cellular and Molecular Connections between Autophagy and Inflammation.
AB  - Autophagy is an intracellular catabolic pathway essential for the recycling of
      proteins and larger substrates such as aggregates, apoptotic corpses, or long
      lived and superfluous organelles whose accumulation could be toxic for cells.
      Because of its unique feature to engulf part of cytoplasm in double-membrane cup
      shaped structures, which further fuses with lysosomes, autophagy is also involved
      in the elimination of host cell invaders and takes an active part of the innate
      and adaptive immune response. Its pivotal role in maintenance of the inflammatory
      balance makes dysfunctions of the autophagy process having important pathological
      consequences. Indeed, defects in autophagy are associated with a wide range of
      human diseases including metabolic disorders (diabetes and obesity), inflammatory
      bowel disease (IBD), and cancer. In this review, we will focus on interrelations
      that exist between inflammation and autophagy. We will discuss in particular how
      mediators of inflammation can regulate autophagy activity and, conversely, how
      autophagy shapes the inflammatory response. Impact of genetic polymorphisms in
      autophagy-related gene on inflammatory bowel disease will be also discussed. 

PMID- 26221065
TI  - New Developments in Cystic Fibrosis Airway Inflammation.

PMID- 26221066
TI  - A New Hidden Markov Model for Protein Quality Assessment Using Compatibility
      Between Protein Sequence and Structure.
AB  - Protein structure Quality Assessment (QA) is an essential component in protein
      structure prediction and analysis. The relationship between protein sequence and
      structure often serves as a basis for protein structure QA. In this work, we
      developed a new Hidden Markov Model (HMM) to assess the compatibility of protein
      sequence and structure for capturing their complex relationship. More
      specifically, the emission of the HMM consists of protein local structures in
      angular space, secondary structures, and sequence profiles. This model has two
      capabilities: (1) encoding local structure of each position by jointly
      considering sequence and structure information, and (2) assigning a global score
      to estimate the overall quality of a predicted structure, as well as local scores
      to assess the quality of specific regions of a structure, which provides useful
      guidance for targeted structure refinement. We compared the HMM model to state-of
      art single structure quality assessment methods OPUSCA, DFIRE, GOAP, and RW in
      protein structure selection. Computational results showed our new score HMM.Z can
      achieve better overall selection performance on the benchmark datasets.

PMID- 26221068
TI  - Identification and Functional Characterization of Cis-Regulatory Elements
      Controlling Expression of the Porcine ADRB2 Gene.
AB  - The beta-2 adrenergic receptor (beta-2 AR) modulates metabolic processes in
      skeletal muscle, liver, and adipose tissue in response to catecholamine
      stimulation. We showed previously that expression of the porcine beta-2 AR gene
      (ADRB2) is affected by cis-regulatory polymorphisms. These are most likely
      responsible for the association of ADRB2 with economically relevant muscle
      related traits in pigs. The present study focused on characterization of promoter
      elements involved in basal transcriptional regulation of the porcine ADRB2 in
      different cell types to aid identification of its cis-regulatory polymorphisms.
      Based on in silico analysis, luciferase reporter gene assays and gel shift assays
      were performed using COS-7, HepG2, C2C12, and 3T3-L1 cells. Deletion mapping of
      the 5' flanking region (-1324 to +33) of ADRB2 revealed the region between -307
      and -269 to be the minimal promoter, including regulatory elements essential for
      the basal transcriptional activity in all four tested cell types. Directly
      upstream (-400 to -323) we identified an important enhancer element required for
      maximal promoter activity. In silico analysis and gel shift assays revealed that
      this GC-rich element harbors two evolutionarily conserved binding sites of Sp1, a
      constitutive transcriptional activator. Significant transcriptional activation of
      the porcine ADRB2 promoter was demonstrated by overexpression of Sp1. Our results
      demonstrate, for the first time, an important role of Sp1 and of the responsive
      enhancer element in the regulation of ADRB2 expression. Polymorphisms located in
      this domain of the porcine ADRB2 promoter represent candidate causal cis
      regulatory variants. 

PMID- 26221067
TI  - MDC1 Enhances Estrogen Receptor-mediated Transactivation and Contributes to
      Breast Cancer Suppression.
AB  - Estrogen receptor alpha (ERalpha) is a key transcriptional factor in the
      proliferation and differentiation in mammary epithelia and has been determined to
      be an important predictor of breast cancer prognosis and therapeutic target.
      Meanwhile, diverse transcriptional co-regulators of ERalpha play crucial and
      complicated roles in breast cancer progression. Mediator of DNA damage checkpoint
      1 (MDC1) has been identified as a critical upstream mediator in the cellular
      response to DNA damage, however, some non-DNA damage responsive functions of MDC1
      haven't been fully defined. In this study, we have identified MDC1 as a co
      activator of ERalpha in breast cancer cells and demonstrated that MDC1 associates
      with ERalpha. MDC1 was also recruited to estrogen response element (ERE) of
      ERalpha target gene. Knockdown of MDC1 reduced the transcription of the
      endogenous ERalpha target genes, including p21. MDC1 depletion led to the
      promotion of breast cancer progression, and the expression of MDC1 is lower in
      breast cancer. Taken together, these results suggested that MDC1 was involved in
      the enhancement of ERalpha-mediated transactivation in breast cancer cells. This
      positive regulation by MDC1 might contribute to the suppression of breast cancer
      progression by acting as a barrier of positive to negative ERalpha function
      transformation. 

PMID- 26221069
TI  - Evolutionary History of Cathepsin L (L-like) Family Genes in Vertebrates.
AB  - Cathepsin L family, an important cysteine protease found in lysosomes, is
      categorized into cathepsins B, F, H, K, L, S, and W in vertebrates. This
      categorization is based on their sequence alignment and traditional functional
      classification, but the evolutionary relationship of family members is unclear.
      This study determined the evolutionary relationship of cathepsin L family genes
      in vertebrates through phylogenetic construction. Results showed that cathepsins
      F, H, S and K, and L and V were chronologically diverged. Tandem-repeat
      duplication was found to occur in the evolutionary history of cathepsin L family.
      Cathepsin L in zebrafish, cathepsins S and K in xenopus, and cathepsin L in mice
      and rats underwent evident tandem-repeat events. Positive selection was detected
      in cathepsin L-like members in mice and rats, and amino acid sites under positive
      selection pressure were calculated. Most of these sites appeared at the
      connection of secondary structures, suggesting that the sites may slightly change
      spatial structure. Severe positive selection was also observed in cathepsin V
      (L2) of primates, indicating that this enzyme had some special functions. Our
      work provided a brief evolutionary history of cathepsin L family and
      differentiated cathepsins S and K from cathepsin L based on vertebrate
      appearance. Positive selection was the specific cause of differentiation of
      cathepsin L family genes, confirming that gene function variation after expansion
      events was related to interactions with the environment and adaptability. 

PMID- 26221070
TI  - DNA-PKcs Negatively Regulates Cyclin B1 Protein Stability through Facilitating
      Its Ubiquitination Mediated by Cdh1-APC/C Pathway.
AB  - The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is a critical
      component of the non-homologous end-joining pathway of DNA double-stranded break
      repair. DNA-PKcs has also been shown recently functioning in mitotic regulation.
      Here, we report that DNA-PKcs negatively regulates the stability of Cyclin B1
      protein through facilitating its ubiquitination mediated by Cdh1 / E 3 ubiquitin
      ligase APC/C pathway. Loss of DNA-PKcs causes abnormal accumulation of Cyclin B1
      protein. Cyclin B1 degradation is delayed in DNA-PKcs-deficient cells as result
      of attenuated ubiquitination. The impact of DNA-PKcs on Cyclin B1 stability
      relies on its kinase activity. Our study further reveals that DNA-PKcs interacts
      with APC/C core component APC2 and its co-activator Cdh1. The destruction of Cdh1
      is accelerated in the absence of DNA-PKcs. Moreover, overexpression of exogenous
      Cdh1 can reverse the increase of Cyclin B1 protein in DNA-PKcs-deficient cells.
      Thus, DNA-PKcs, in addition to its direct role in DNA damage repair, functions in
      mitotic progression at least partially through regulating the stability of Cyclin
      B1 protein. 

PMID- 26221071
TI  - Identification and Characterization of Candidate Chemosensory Gene Families from
      Spodoptera exigua Developmental Transcriptomes.
AB  - Insect chemosensory genes have been considered as potential molecular targets to
      develop alternative strategies for pest control. However, in Spodoptera exigua, a
      seriously polyphagous agricultural pest, only a small part of such genes have
      been identified and characterized to date. Here, using a bioinformatics screen a
      total of 79 chemosensory genes were identified from a public transcriptomic data
      of different developmental stages (eggs, 1st to 5th instar larvae, pupae, female
      and male adults), including 34 odorant binding proteins (OBPs), 20 chemosensory
      proteins (CSPs), 22 chemosensory receptors (10 odorant receptors (ORs), six
      gustatory receptors (GRs) and six ionotropic receptors (IRs)) and three sensory
      neuron membrane proteins (SNMPs). Notably, a new group of lepidopteran SNMPs
      (SNMP3 group) was found for the first time in S. exigua, and confirmed in four
      other moth species. Further, reverse transcription PCR (RT-PCR) and quantitative
      real time PCR (qPCR) were employed respectively to validate the sequences and
      determine the expression patterns of 69 identified chemosensory genes regarding
      to sexes, tissues and stages. Results showed that 67 of these genes could be
      detected and reconstructed in at least one tissue tested. Further, 60
      chemosensory genes were expressed in adult antennae and 52 in larval heads with
      the antennae, whereas over half of the genes were also detected in non-olfactory
      tissues like egg and thorax. Particularly, S. exigua OBP2 showed a predominantly
      larval head-biased expression, and functional studies further indicated its
      potentially olfactory roles in guiding food searching of larvae. This work
      suggests functional diversities of S. exigua chemosensory genes and could greatly
      facilitate the understanding of olfactory system in S. exigua and other
      lepidopteran species. 

PMID- 26221072
TI  - Higher Frequency of Circulating PD-1(high) CXCR5(+)CD4(+) Tfh Cells in Patients
      with Chronic Schistosomiasis.
AB  - The current knowledge of immunological responses to schistosomiasis is
      insufficient for the development of vaccine and therapies. The role of T
      follicular helper (Tfh) cells in schistosome infections is not fully defined. The
      frequency of circulating Tfh cells and serum cytokine levels were analyzed in 11
      patients with chronic schistosomiasis and 10 healthy controls (HC), who reside in
      an endemic area for Schistosomiasis japonicum. Significantly higher frequencies
      of circulating CXCR5(+) CD4(+) Tfh cells and higher expression levels of ICOS and
      PD-1 in CXCR5(+) CD4(+) Tfh cells were observed in patients with chronic
      schistosomiasis compared to HC. The levels of IL-21 in serum and the expression
      of IL-21 mRNA were higher in chronic schistosomiasis patients than in HC.
      Moreover, the frequency of circulating PD-1(high) CXCR5(+) CD4(+) Tfh cells
      positively correlated with the levels of IL-21 in serum from patients with
      chronic schistosomiasis. A positive correlation was also found between the
      frequency of PD-1(high) CXCR5(+) CD4(+) Tfh cells and the levels of soluble egg
      antigen (SEA)-specific antibodies in serum samples from the patient group. Our
      study is the first regarding Tfh cells in chronic human schistosomiasis and the
      finding indicate that PD-1(high) CXCR5(+) CD4(+)Tfh cells might play an important
      role in the production of specific antibodies in schistosomiasis. This study
      contributes to the understanding of immune response to schistosomiasis and may
      provide helpful support in vaccine development. 

PMID- 26221073
TI  - Knockout of SRC-1 and SRC-3 in Mice Decreases Cardiomyocyte Proliferation and
      Causes a Noncompaction Cardiomyopathy Phenotype.
AB  - Noncompaction cardiomyopathy (NCC) is a congenital heart disease that causes
      ventricular dysfunction and high mortality rate in children. The mechanisms
      responsible for NCC are still unknown. The steroid receptor coactivator-1 (SRC-1)
      and SRC-3 are transcriptional coactivators for nuclear hormone receptors and
      certain other transcription factors that regulate many genes in development and
      organ function. However, the roles of SRC-1/3 in heart morphogenesis, function
      and NCC occurrence are unknown. This study aims to examine the spatial and
      temporal expression patterns of SRC-1/3 in the heart and investigate the specific
      roles of SRC-1/3 in heart development, function and NCC occurrence.
      Immunochemical analysis detected SRC-1/3 expressions in the proliferating
      cardiomyocytes of mouse heart at prenatal and neonatal stages, while these
      expressions disappeared within two weeks after birth. Through generating and
      characterizing mouse lines with global or cardiomyocyte-specific knockouts of SRC
      1/3, we found ablation of SRC-1/3 in the myocardial lineage resulted in prominent
      trabeculae, deep intertrabecular recesses and thin ventricular wall and septum.
      These developmental defects caused a failure of trabecular compaction, decreased
      internal ventricular dimension, reduced cardiac ejection fraction and output and
      led to a high rate of postnatal mortality. Collectively, these structural and
      functional abnormalities closely simulate the phenotype of NCC patients. Further
      molecular analysis of cardiomyocytes in vivo and in vitro revealed that SRC-1/3
      directly up-regulate cyclin E2, cyclin B1 and myocardin to promote cardiomyocyte
      proliferation and differentiation. In conclusion, SRC-1/3 are required for
      cardiomyocyte proliferation and differentiation at earlier developmental stages,
      and their dysfunction causes NCC-like abnormalities in the hearts of newborn and
      adult mice. 

PMID- 26221074
TI  - Cathepsin B Cysteine Proteinase is Essential for the Development and Pathogenesis
      of the Plant Parasitic Nematode Radopholus similis.
AB  - Radopholus similis is an important plant parasitic nematode which severely harms
      many crops. Cathepsin B is present in a wide variety of organisms, and plays an
      important role in many parasites. Understanding cathepsin B of R. similis would
      allow us to find new targets and approaches for its control. In this study, we
      found that Rs-cb-1 mRNA was expressed in esophageal glands, intestines and gonads
      of females, testes of males, juveniles and eggs in R. similis. Rs-cb-1 expression
      was the highest in females, followed by juveniles and eggs, and was the lowest in
      males. The maximal enzyme activity of Rs-CB-1 was detected at pH 6.0 and 40 
      degrees C. Silencing of Rs-cb-1 using in vitro RNAi (Soaking with dsRNA in vitro)
      not only significantly inhibited the development and hatching of R. similis, but
      also greatly reduced its pathogenicity. Using in planta RNAi, we confirmed that
      Rs-cb-1 expression in nematodes were significantly suppressed and the resistance
      to R. similis was significantly improved in T2 generation transgenic tobacco
      plants expressing Rs-cb-1 dsRNA. The genetic effects of in planta RNAi-induced
      gene silencing could be maintained in the absence of dsRNA for at least two
      generations before being lost, which was not the case for the effects induced by
      in vitro RNAi. Overall, our results first indicate that Rs-cb-1 plays key roles
      in the development, hatching and pathogenesis of R. similis, and that in planta
      RNAi is an effective tool in studying gene function and genetic engineering of
      plant resistance to migratory plant parasitic nematodes. 

PMID- 26221075
TI  - The Small Molecule R-(-)-beta-O-Methylsynephrine Binds to Nucleoporin 153 kDa and
      Inhibits Angiogenesis.
AB  - R-(-)-beta-O-methylsynephrine (OMe-Syn) is a naturally occurring small molecule
      that was identified in a previous screen as an inhibitor of angiogenesis. In this
      study, we conducted two animal model experiments to investigate the in vivo
      antiangiogenic activity of OMe-Syn. OMe-Syn significantly inhibited angiogenesis
      in a transgenic zebrafish model as well as in a mouse retinopathy model. To
      elucidate the underlying mechanisms responsible for the antiangiogenic activity
      of OMe-Syn, we used phage display cloning to isolate potential OMe-Syn binding
      proteins from human cDNA libraries and identified nucleoporin 153 kDa (NUP153) as
      a primary binding partner of OMe-Syn. OMe-Syn competitively inhibited mRNA
      binding to the RNA-binding domain of NUP153. Furthermore, depletion of NUP153 in
      human cells or zebrafish embryos led to an inhibition of angiogenesis, in a
      manner similar to that seen in response to OMe-Syn treatment. These data suggest
      that OMe-Syn is a promising candidate for the development of a novel
      antiangiogenic agent and that inhibition of NUP153 is possibly responsible for
      the antiangiogenic activity of OMe-Syn. 

PMID- 26221078
TI  - Clinical supervision in primary health care; experiences of district nurses as
      clinical supervisors - a qualitative study.
AB  - BACKGROUND: Learning in the clinical environment is an important part of nursing
      education. Several recent studies focusing on clinical learning have been based
      on hospital settings. Little is known about primary health care (PHC) as clinical
      environment where district nurses (DNs) or nurses supervise students. It is
      important to understand more about opportunities and difficulties in supervising
      in this area in order to develop PHC as an optimal learning environment for
      nursing students. The main objective of this study was to gain an understanding
      of supervisors' experiences of supervising undergraduate students at PHC units.
      METHODS: A qualitative research approach was used to collect data and analyse
      supervisors' experiences. Six focus groups were carried out with 24 supervisors.
      Focus group data were audio-taped. The data were analysed using an inductive
      content analysis. RESULTS: Three themes illustrated supervisors' experiences:
      abandonment, ambivalence and sharing the holistic approach. Supervisors felt
      abandoned by their managers, colleagues and nurse teachers from universities.
      They experienced ambivalence due to simultaneously being supervisors for students
      and carrying out their daily work with patients. At the same time, they were
      proud to be DNs and willing to share their unique role to apply a holistic
      approach and continuity in patient care with students. CONCLUSION: When
      supervising students in PHC, social support and communication between supervisors
      and their colleagues and management as well as nurse teachers need to be taken
      into consideration both at universities and at primary health care units.

PMID- 26221077
TI  - Norisoboldine, an Anti-Arthritis Alkaloid Isolated from Radix Linderae,
      Attenuates Osteoclast Differentiation and Inflammatory Bone Erosion in an Aryl
      Hydrocarbon Receptor-Dependent Manner.
AB  - Norisoboldine (NOR), the primary isoquinoline alkaloid constituent of the root of
      Lindera aggregata, has previously been demonstrated to attenuate osteoclast (OC)
      differentiation. Accumulative evidence has shown that aryl hydrocarbon receptor
      (AhR) plays an important role in regulating the differentiation of various cells,
      and multiple isoquinoline alkaloids can modulate AhR. In the present study, we
      explored the role of NOR in the AhR signaling pathway. These data showed that the
      combination of AhR antagonist resveratrol (Res) or alpha-naphthoflavone (alpha
      NF) nearly reversed the inhibition of OC differentiation through NOR. NOR could
      stably bind to AhR, up-regulate the nuclear translocation of AhR, and enhance the
      accumulation of the AhR-ARNT complex, AhR-mediated reporter gene activity and
      CYP1A1 expression in RAW 264.7 cells, suggesting that NOR might be an agonist of
      AhR. Moreover, NOR inhibited the nuclear translocation of NF-kappaB-p65,
      resulting in the evident accumulation of the AhR-NF-kappaB-p65 complex, which
      could be markedly inhibited through either Res or alpha-NF. Although NOR only
      slightly affected the expression of HIF-1alpha, NOR markedly reduced VEGF mRNA
      expression and ARNT-HIF-1alpha complex accumulation. In vivo studies indicated
      that NOR decreased the number of OCs and ameliorated the bone erosion in the
      joints of rats with collagen-induced arthritis, accompanied by the up-regulation
      of CYP1A1 and the down-regulation of VEGF mRNA expression in the synovium of
      rats. A combination of alpha-NF nearly completely reversed the effects of NOR. In
      conclusion, NOR attenuated OC differentiation and bone erosion through the
      activation of AhR and the subsequent inhibition of both NF-kappaB and HIF
      pathways. 

PMID- 26221079
TI  - Multidrug resistance characterization in multicellular tumour spheroids from two
      human lung cancer cell lines.
AB  - BACKGROUND: Most of the knowledge about the mechanisms of multidrug resistance in
      lung cancer has been achieved through the use of cell lines isolated from tumours
      cultivated either in suspensions of isolated cells or in monolayers and following
      exposition to different cytostatic agents. However, tumour cell lines growing as
      multicellular tumour spheroids (MTS) frequently develop multicellular resistance
      in a drug-independent form. The aim of this study was to characterize the
      phenotypic and functional differences between two human NSCLC cell lines (INER-37
      and INER-51) grown as traditional monolayer cultures versus as MTS. METHODS:
      After 72 hours treatment with anticancer drugs, chemosensitivity in monolayers
      and tumour spheroids cultures was assessed using MTT assay. Reverse transcription
      polymerase chain reaction was employed to detect the mRNAs of multidrug
      resistance-related genes. The expression of P-gp was analyzed by
      immunohistochemical staining and cell cycle profiles were analyzed using FACS.
      RESULTS: The results indicate that when grown as MTS each lung cancer cell line
      had different morphologies as well as and abrogation of cell proliferation with
      decrease of the G2/M phase. Also, MTS acquired multicellular resistance to
      several chemotherapeutic agents in only a few days of culture which were
      accomplished by significant changes in the expression of MDR-related genes.
      CONCLUSION: Overall, the MTS culture changed the cellular response to drugs
      nevertheless each of the cell lines studied seems to implement different
      mechanisms to acquire multicellular resistance.

PMID- 26221076
TI  - Targeting Apoptosis and Multiple Signaling Pathways with Icariside II in Cancer
      Cells.
AB  - Cancer is the second leading cause of deaths worldwide. Despite concerted efforts
      to improve the current therapies, the prognosis of cancer remains dismal. Highly
      selective or specific blocking of only one of the signaling pathways has been
      associated with limited or sporadic responses. Using targeted agents to inhibit
      multiple signaling pathways has emerged as a new paradigm for anticancer
      treatment. Icariside II, a flavonol glycoside, is one of the major components of
      Traditional Chinese Medicine Herba epimedii and possesses multiple biological and
      pharmacological properties including anti-inflammatory, anti-osteoporosis, anti
      oxidant, anti-aging, and anticancer activities. Recently, the anticancer activity
      of Icariside II has been extensively investigated. Here, in this review, our aim
      is to give our perspective on the current status of Icariside II, and discuss its
      natural sources, anticancer activity, molecular targets and the mechanisms of
      action with specific emphasis on apoptosis pathways which may help the further
      design and conduct of preclinical and clinical trials. Icariside II has been
      found to induce apoptosis in various human cancer cell lines of different origin
      by targeting multiple signaling pathways including STAT3, PI3K/AKT, MAPK/ERK, COX
      2/PGE2 and beta-Catenin which are frequently deregulated in cancers, suggesting
      that this collective activity rather than just a single effect may play an
      important role in developing Icariside II into a potential lead compound for
      anticancer therapy. This review suggests that Icariside II provides a novel
      opportunity for treatment of cancers, but additional investigations and clinical
      trials are still required to fully understand the mechanism of therapeutic
      effects to further validate it in anti-tumor therapy. 

PMID- 26221080
TI  - Protective effects of thalidomide on pulmonary injuries in a rat model of
      paraquat intoxication.
AB  - BACKGROUND: This study was designed to evaluate the protective effects of
      thalidomide on paraquat (PQ)-induced lung injuries in a rat model and to explore
      the underlying mechanisms. METHODS: Rats were exposed to 50 mg/kg PQ by oral
      gavage, and treated with thalidomide through oral administration at 60 mg/kg once
      a day, 6 days/week for 2 weeks. Serum levels of IL-6, TNF-alpha, TGFbeta1 and
      COL1A1 were detected at different time points after paraquat exposure. At the end
      of the study, lung tissues were collected for pathological inspection as well as
      analyses of water content and expression levels of IL-6, TNF-alpha, TGFbeta1 and
      COL1A1 mRNA. RESULTS: The results showed that thalidomide treatment could
      significantly alleviate PQ-induced pathological changes in lung tissue and
      severity of lung edema. Thalidomide treatment after PQ exposure resulted in
      significantly reduced serum levels of IL-6, TNF-alpha, TGF-beta1 and COL1A1, as
      compared to PQ group. PCR analysis demonstrated that expression levels of IL-6,
      TNF-alpha, TGF-beta1 and COL1A1 in lung tissue were significantly increased after
      PQ exposure but reduced by thalidomide, which were confirmed by
      immunohistochemistry staining. CONCLUSIONS: Our results indicated that
      inflammatory factors played important roles in PQ-induced lung injuries and
      thalidomide could protect rats from PQ-induced lung injuries by inhibiting the
      upregulation of inflammatory factors.

PMID- 26221081
TI  - Pharmacological mechanism underlying anti-inflammatory properties of two
      structurally divergent coumarins through the inhibition of pro-inflammatory
      enzymes and cytokines.
AB  - BACKGROUND: The aim of the present study is to investigate the effects of two
      structurally divergent coumarins, calipteryxin (1) and (3'S,4'S)-3',4'
      disenecioyloxy-3',4'-dihydroseselin (2) from Seseli recinosum, in
      lipopolysaccharide (LPS)-stimulated murine macrophages. METHODS: The nitrite
      production was evaluated using Griess reagent. The protein and mRNA expression
      levels were investigated through Western blot and quantitative real time-PCR
      analyses. The NF-kappaB and AP-1 DNA-binding activities were assessed using an
      electrophoretic mobility shift assay. The docking studies were performed with
      Glide XP in Schrodinger suite (version 2013). RESULTS: The results of the present
      study revealed that calipteryxin (1) and (3'S,4'S)-3',4'-disenecioyloxy-3',4'
      dihydroseselin (2) treatment showed potent inhibitory effects on pro-inflammatory
      enzymes and cytokines associated with molecular signaling pathways. Treatment
      with calipteryxin and (3'S,4'S)-3',4'-disenecioyloxy-3',4'-dihydroseselin also
      decreased the production of nitric oxide (NO), tumor necrosis factor alpha (TNF
      alpha) and interleukin-1 beta (IL-1beta) in a dose-dependent manner.
      Additionally, both coumarins inhibited the LPS-induced protein and mRNA
      expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in
      RAW264.7 cells. To explore the potential mechanisms underlying the inhibitory
      activity of coumarin derivatives, the protein signaling pathways for NF-kappaB,
      mitogen-activated protein kinase (MAPK) and Akt were examined. Calipteryxin and
      (3'S,4'S)-3',4'-disenecioyloxy-3',4'-dihydroseselin markedly reduced the LPS
      stimulated phosphorylation of IKKalpha/beta, p-IkappaBalpha and IkappaBalpha
      degradation as well as the nuclear translocation of the p65 subunit of pro
      inflammatory transcription factor NF-kappaB. In addition, calipteryxin and
      (3'S,4'S)-3',4'-disenecioyloxy-3',4'-dihydroseselin) considerably inhibited the
      LPS-induced expression of ERK, c-Jun N-terminal kinase (JNK), p38 and Akt
      proteins. Furthermore, both coumarins significantly inhibited c-Jun expression in
      the nucleus. CONCLUSIONS: Taken together, these results support the therapeutic
      potential and molecular mechanism of calipteryxin and (3'S,4'S)-3',4'
      disenecioyloxy-3',4'-dihydroseselin associated with inflammatory diseases.

PMID- 26221082
TI  - Accurate ab Initio Study on the Hydrogen-Bond Pairs in Protein Secondary
      Structures.
AB  - Ab initio calculations up to the MP2/aug-cc-pVQZ//MP2/6-311+G** level have been
      carried out to characterize the four patterns of hydrogen-bond (H-bond) pairs in
      protein secondary structures. The unblocked and methyl-blocked glycine dipeptide
      dimers were arranged to model the H-bond pairs in alpha-helix (alphaHH) and
      antiparallel (Abetabeta-C5 and Abetabeta-C7) and parallel beta-sheet (Pbetabeta)
      secondary structures. The study uncovers that, in addition to the primary CO?NH H
      bonds and the crossing secondary interactions, the CH?OC H-bonds and the tertiary
      effect (as we call it) also contribute substantially. The tertiary effect is due
      to the interpolarization between the donor and acceptor of a H-bond. This effect,
      which enhances the dipole-dipole interactions between two nearby H-bonds,
      stabilizes the beta-sheet-like but destabilizes the helix-like H-bond pairs. The
      MP2 binding energies of the complexes were further refined by extrapolating to
      the complete basis set limit (CBS) according to Truhlar and co-workers and by a
      three-basis-set-based method. The best extrapolated CBS(aD-aT-aQ) binding
      energies of the unblocked dimers are -13.1 (alphaHH), -11.3 (Abetabeta-C5), -19.2
      (Abetabeta-C7), and -14.8 kcal/mol (Pbetabeta). For the methyl-blocked
      counterparts, the best extrapolated CBS(D-T-Q) binding energies are -14.8, -13.4,
      -20.8, and -16.7 kcal/mol, respectively. The interactions in the parallel beta
      conformations are very close to the averages of the C5 and C7 antiparallel beta
      conformations, and both are stronger than the helical dimers. Because the
      additive force fields are unable to account for the tertiary effect owing to the
      lack of polarization, all examined additive force fields significantly
      overestimate the interaction energies of the helix conformations relative to the
      beta-sheet conformations. Notably, the agreement between molecular mechanical and
      quantum mechanical binding energies is improved after turning on the
      polarization. The study provides reference ab initio structures and binding
      energies for characterizing the backbone H-bonds of the protein secondary
      structures, which can be used for the parametrization of empirical molecular
      mechanics force fields.

PMID- 26221083
TI  - Antibiotic resistance and integrons in Shiga toxin-producing Escherichia coli
      (STEC).
AB  - Shiga toxin-producing Escherichia coli (STEC) cause hemorrhagic colitis (HC) and
      hemolytic-uremic syndrome in humans (HUS). Cattle are the main reservoir of STEC
      and transmission to humans occurs through contaminated food and water.
      Antibiotics are used in pig production systems to combat disease and improve
      productivity and play a key role in the dissemination of antibiotic resistance
      genes to the bacteria. Integrons have been identified in resistant bacteria
      allowing for the acquisition and dissemination of antibiotic resistance genes.
      STEC strains isolated from humans and animals have developed antibiotic
      resistance. In our laboratory, 21 non-157 STEC strains isolated from pigs were
      analyzed to detect class 1 and 2 integrons by PCR. Eight carried integrons, 7 of
      them harbored intl2. In another study 545 STEC strains were also analyzed for the
      presence of intl1 and intl2 . Strains carrying intl1 belonged to isolates from
      environment (n = 1), chicken hamburger (n = 2), dairy calves (n = 4) and pigs (n
      = 8). Two strains isolated from pigs harbored intl2 and only one intl1 / intl2 ,
      highlighting the presence of intl2 in pigs. The selection for multiresistant
      strains may contribute to the emergence of antibiotic resistant pathogens and
      facilitate the spreading of the mobile resistance elements to other bacteria. 

PMID- 26221085
TI  - Chemical modification of Aspergillus niger beta-glucosidase and its catalytic
      properties.
AB  - Aspergillus niger beta-glucosidase was modified by covalent coupling to periodate
      activated polysaccharides (glycosylation). The conjugated enzyme to activated
      starch showed the highest specific activity (128.5 U/mg protein). Compared to the
      native enzyme, the conjugated form exhibited: a higher optimal reaction
      temperature, a lower Ea (activation energy), a higher K m (Michaelis constant)
      and Vmax (maximal reaction rate), and improved thermal stability. The calculated
      t 1/2 (half-life) values of heat in-activation at 60  degrees C and 70  degrees C
      were 245.7 and 54.5 min respectively, whereas at these temperatures the native
      enzyme was less stable (t 1/2 of 200.0 and 49.5 min respectively). The conjugated
      enzyme retained 32.3 and 29.7%, respectively from its initial activity in
      presence of 5 mM Sodium Dodecyl Sulphate (SDS) and p -Chloro Mercuri Benzoate ( p
      -CMB), while the native enzyme showed a remarkable loss of activity (retained
      activity 1.61 and 13.7%, respectively). The present work has established the
      potential of glycosylation to enhance the catalytic properties of beta
      glucosidase enzyme, making this enzyme potentially feasible for biotechnological
      applications. 

PMID- 26221084
TI  - Bioremediation of polyaromatic hydrocarbons (PAHs) using rhizosphere technology.
AB  - The remediation of polluted sites has become a priority for society because of
      increase in quality of life standards and the awareness of environmental issues.
      Over the past few decades there has been avid interest in developing in situ
      strategies for remediation of environmental contaminants, because of the high
      economic cost of physicochemical strategies, the biological tools for remediation
      of these persistent pollutants is the better option. Major foci have been
      considered on persistent organic chemicals i.e. polyaromatic hydrocarbons (PAHs)
      due to their ubiquitous occurrence, recalcitrance, bioaccumulation potential and
      carcinogenic activity. Rhizoremediation, a specific type of phytoremediation that
      involves both plants and their associated rhizospheric microbes is the creative
      biotechnological approach that has been explored in this review. Moreover, in
      this review we showed the significance of rhizoremediation of PAHs from other
      bioremediation strategies i.e. natural attenuation, bioaugmentation and
      phytoremediation and also analyze certain environmental factor that may influence
      the rhizoremediation technique. Numerous bacterial species were reported to
      degrade variety of PAHs and most of them are isolated from contaminated soil,
      however few reports are available from non contaminated soil. Pseudomonas
      aeruginosa , Pseudomons fluoresens , Mycobacterium spp., Haemophilus spp.,
      Rhodococcus spp., Paenibacillus spp. are some of the commonly studied PAH
      degrading bacteria. Finally, exploring the molecular communication between plants
      and microbes, and exploiting this communication to achieve better results in the
      elimination of contaminants, is a fascinating area of research for future
      perspective.

PMID- 26221086
TI  - Epiphytic marine pigmented bacteria: A prospective source of natural
      antioxidants.
AB  - Awareness on antioxidants and its significance in human healthcare has increased
      many folds in recent time. Increased demand requisite on welcoming newer and
      alternative resources for natural antioxidants. Seaweed associated pigmented
      bacteria screened for its antioxidant potentials reveals 55.5% of the organisms
      were able to synthesize antioxidant compounds. DPPH assay showed 20% of the
      organisms to reach a antioxidant zone of 1 cm and 8.3% of the strains more than 3
      cm. Pseudomonas koreensis (JX915782) a Sargassum associated yellowish brown
      pigmented bacteria have better activity than known commercial antioxidant
      butylated hydroxytoluene (BHT) against DPPH scavenging. Serratia rubidaea
      (JX915783), an associate of Ulva sp. and Pseudomonas argentinensis (JX915781) an
      epiphyte of Chaetomorpha media , were also contributed significantly towards ABTS
      (7.2% +/- 0.03 to 15.2 +/- 0.09%; 1.8% +/- 0.01 to 15.7 +/- 0.22%) and FRAP (1.81
      +/- 0.01 to 9.35 +/- 0.98; 7.97 +/- 0.12 to 18.70 +/- 1.84 MUg/mL of AsA Eq.)
      respectively. 16S rRNA gene sequence analysis revealed bacteria that have higher
      antioxidant activity belongs to a bacterial class Gammaproteobacteria.
      Statistical analysis of phenolic contents in relation with other parameters like
      DPPH, ABTS, reducing power and FRAP are well correlated (p < 0.05). Results
      obtained from the current study inferred that the seaweed associated pigmented
      bacteria have enormous potential on antioxidant compounds and need to be
      extracted in a larger way for clinical applications.

PMID- 26221087
TI  - Characterization and antimicrobial performance of nano silver coatings on leather
      materials.
AB  - In this study, the characterization and the antimicrobial properties of nano
      silver (nAg) coating on leather were investigated. For this purpose, turbidity,
      viscosity and pH of nAg solutions prepared by the sol-gel method were measured.
      The formation of films from these solutions was characterized according to
      temperature by Differential Thermal Analysis-Thermogravimetry (DTA-TG) equipment.
      The surface morphology of treated leathers was observed using Scanning Electron
      Microscopy (SEM). The antimicrobial performance of nAg coatings on leather
      materials to the test microorganisms as Escherichia coli , Staphylococcus aureus
      , Candida albicans and Aspergillius niger was evaluated by the application of
      qualitative (Agar overlay method) and quantitative (percentage of microbial
      reduction) tests. According to qualitative test results it was found that 20
      MUg/cm (2) and higher concentrations of nAg on the leather samples were effective
      against all microorganisms tested. Moreover, quantitative test results showed
      that leather samples treated with 20 MUg/cm (2) of nAg demonstrated the highest
      antibacterial activity against E. coli with 99.25% bacterium removal, whereas a
      10 MUg/cm (2) concentration of nAg on leather was enough to exhibit the excellent
      percentage reduction against S. aureus of 99.91%. The results are promising for
      the use of colloidal nano silver solution on lining leather as antimicrobial
      coating. 

PMID- 26221088
TI  - Endophytic fungi from medicinal plant Bauhinia forficata: Diversity and
      biotechnological potential.
AB  - Bauhinia forficata is native to South America and used with relative success in
      the folk medicine in Brazil. The diversity, antibacterial activity, and
      extracellular hydrolytic enzymes of endophytic fungi associated with this plant
      were studied. Plant samples, which included leaves, sepals, stems, and seeds,
      were used. Ninety-five endophytic fungal were isolated (18 from leaves, 22 from
      sepals, 46 from stems, and nine from seeds), comprising 28 species. The most
      frequently isolated species were Acremonium curvulum (9.5%), Aspergillus
      ochraceus (7.37%), Gibberella fujikuroi (10.53%), Myrothecium verrucaria (10.53%)
      and Trichoderma piluliferum (7.37%). Diversity and species richness were higher
      in stem tissues, and Sorensen's index of similarity between the tissues was low.
      Eleven fungi showed antibacterial activity. Aspergillus ochraceus , Gibberella
      baccata , Penicillium commune , and P. glabrum were those with the greatest
      antibacterial activity against Staphylococcus aureus and/or Streptococcus
      pyogenes . Thirteen species showed proteolytic activity, particularly Phoma
      putaminum . Fourteen species were cellulase positive, particularly the
      Penicillium species and Myrmecridium schulzeri . All isolates tested were
      xylanase positive and 10 showed lipolytic activity, especially Penicillium
      glabrum . It is clear that the endophytic fungi from B. forficata have potential
      for the production of bioactive compounds and may be a source of new therapeutic
      agents for the effective treatment of diseases in humans, other animals, and
      plants. To our knowledge, this is the first study of endophytic fungi from
      different tissues of B. forficata and their biotechnological potential.

PMID- 26221089
TI  - Laccase produced by a thermotolerant strain of Trametes trogii LK13.
AB  - Thermophilic and thermotolerant micro-organisms strains have served as the
      natural source of industrially relevant and thermostable enzymes. Although some
      strains of the Trametes genus are thermotolerant, few Trametes strains were
      studied at the temperature above 30  degrees C until now. In this paper, the
      laccase activity and the mycelial growth rate for Trametes trogii LK13 are
      superior at 37  degrees C. Thermostability and organic cosolvent tolerance assays
      of the laccase produced at 37  degrees C indicated that the enzyme possessed fair
      thermostability with 50% of its initial activity at 80  degrees C for 5 min, and
      could remain 50% enzyme activity treated with organic cosolvent at the
      concentration range of 25%-50% (v/v). Furthermore, the test on production of
      laccase and lignocellulolytic enzymes showed the crude enzymes possessed high
      laccase level (1000 U g (-1) ) along with low cellulose (2 U g (-1) ) and
      xylanase (140 U g (-1) ) activity. Thus, T. trogii LK13 is a potential strain to
      be applied in many biotechnological processes.

PMID- 26221090
TI  - Effect of surfactants and temperature on germination and vegetative growth of
      Beauveria bassiana.
AB  - Three non-ionic surfactants: Tween20, Tween80 and Breakthru ((r)) were screened
      for their effects on spore germination and mycelial growth rates and for their
      influence on three isolates of Beauveria bassiana spore germination at various
      temperatures. Tween20 and Tween80 were compatible with all the B. bassiana
      isolates in the germination studies, but inhibited germination at higher
      surfactant concentrations, irrespective of the conidial concentrations .
      Breakthru ((r)) had an inhibitory effect on germination even at the lowest
      concentration of 0.1% on all the B. bassiana isolates. The effects of the
      surfactants on spore germination did not correspond with their effects on colony
      growth. Conidial viability within the same formulation declined significantly
      with increases in temperature, irrespective of the surfactant. The optimal
      temperature for conidial germination of B. bassiana isolates was approximately 25
      degrees C with an upper limit at 30  degrees C. Isolate 7320 was identified as
      the least affected by the different surfactants. This isolate was able to
      germinate rapidly in a broad temperature range of 25-30  degrees C after 24 h,
      this characteristic being an essential factor in controlling house fly
      populations in poultry houses.

PMID- 26221091
TI  - Microalgae population dynamics in photobioreactors with secondary sewage effluent
      as culture medium.
AB  - Nitrogen and phosphorus present in sewage can be used for microalgae growth,
      possibiliting cost reduction in the production of microalgae at the same time
      that it decreases the eutrophication potential of the effluent. This research
      aimed at monitoring the native community of microalgae and coliform bacteria in a
      secondary effluent from anaerobic municipal sewage treatment. Two treatments
      (aerated and non-aerated) were performed to grow microalgae under semi-controlled
      conditions in semi-closed photobioreactors in a greenhouse. The results showed no
      significant pH and coliforms (total and Escherichia coli ) variation between
      treatments. Nutrient concentrations were reduced supporting microalgae growth up
      to 10 (7) cells.mL (-1) independent of aeration. Exponential growth was obtained
      from the first day for the non-aerated, but a 5 day lag phase of growth was
      obtained for the aerated. Chlorella vulgaris was the dominant microalgae (99.9%)
      in both treatments. In the aerated, 5 algae classes were detected (Chlorophyceae,
      Cyanophyceae, Chrysophyceae, Bacillariophyceae and Euglenophyceae), with 12 taxa,
      whereas in the non-aerated, 2 classes were identified (Chlorophyceae and
      Cyanophyceae), with 5 taxa. We concluded that effluent is viable for microalgae
      growth, especially Chlorella vulgaris, at the same time that the eutrophication
      potential and coliforms are decreased, contributing for better quality of the
      final effluent. 

PMID- 26221092
TI  - Occurrence of culturable soil fungi in a tropical moist deciduous forest
      Similipal Biosphere Reserve, Odisha, India.
AB  - Similipal Biosphere Reserve (SBR) is a tropical moist deciduous forest dominated
      by the species Shorea robusta . To the best of our knowledge their rich
      biodiversity has not been explored in term of its microbial wealth. In the
      present investigation, soil samples were collected from ten selected sites inside
      SBR and studied for their physicochemical parameters and culturable soil fungal
      diversity. The soil samples were found to be acidic in nature with a pH ranging
      from of 5.1-6.0. Highest percentage of organic carbon and moisture content were
      observed in the samples collected from the sites, Chahala-1 and Chahala-2. The
      plate count revealed that fungal population ranged from 3.6 * 10 (4) -2.1 * 10
      (5) and 5.1 * 10 (4) -4.7 * 10 (5) cfu/gm of soil in summer and winter seasons
      respectively. The soil fungus, Aspergillus niger was found to be the most
      dominant species and Species Important Values Index (SIVI) was 43.4 and 28.6 in
      summer and winter seasons respectively. Among the sites studied, highest fungal
      diversity indices were observed during summer in the sites, Natto-2 and Natto-1.
      The Shannon-Wiener and Simpson indices in these two sites were found to be 3.12
      and 3.022 and 0.9425 and 0.9373 respectively. However, the highest Fisher's alpha
      was observed during winter in the sites Joranda, Natto-2, Chahala-1 and Natto-1
      and the values were 3.780, 3.683, 3.575 and 3.418 respectively. Our investigation
      revealed that, fungal population was dependent on moisture and organic carbon (%)
      of the soil but its diversity was found to be regulated by sporulating species
      like Aspergillus and Penicillium.

PMID- 26221093
TI  - Bacteria in combination with fertilizers promote root and shoot growth of maize
      in saline-sodic soil.
AB  - Salinity is the leading abiotic stress hampering maize ( Zea mays L.) growth
      throughout the world, especially in Pakistan. During salinity stress, the
      endogenous ethylene level in plants increases, which retards proper root growth
      and consequent shoot growth of the plants. However, certain bacteria contain the
      enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase, which converts 1
      aminocyclopropane-1-carboxylic acid (an immediate precursor of ethylene
      biosynthesis in higher plants) into ammonia and alpha-ketobutyrate instead of
      ethylene. In the present study, two Pseudomonas bacterial strains containing ACC
      deaminase were tested separately and in combinations with mineral fertilizers to
      determine their potential to minimize/undo the effects of salinity on maize
      plants grown under saline-sodic field conditions. The data recorded at 30, 50 and
      70 days after sowing revealed that both the Pseudomonas bacterial strains
      improved root and shoot length, root and shoot fresh weight, and root and shoot
      dry weight up to 34, 43, 35, 71, 55 and 68%, respectively, when applied without
      chemical fertilizers: these parameter were enhanced up to 108, 95, 100, 131, 100
      and 198%, respectively, when the strains were applied along with chemical
      fertilizers. It can be concluded that ACC-deaminase Pseudomonas bacterial strains
      applied alone and in conjunction with mineral fertilizers improved the root and
      shoot growth of maize seedlings grown in saline-sodic soil. 

PMID- 26221094
TI  - Degradation of 2,4,6-trinitrotoluene by P. aeruginosa and characterization of
      some metabolites.
AB  - Degradation of 2,4,6-trinitrotoluene (TNT), a nitroaromatic explosive found in
      the soil and ground water, was investigated using Pseudomonas aeruginosa in in
      vitro experiments . Biodegradable abilitiy of this bacteria was performed with 50
      and 75 mg L (-1) TNT concentrations in a defined liquid medium for 96 h time
      period. Treatment of TNT in supernatant samples taken at 0, 6, 12, 24, 48, 72 and
      96 h from agitated vessels was followed by reverse-phase high-performance liquid
      chromatography (HPLC). In cultures supplemented with 50 and 75 mgL (-1) TNT,
      after 96 h of incubation 46% and 59% reduction were detected respectively. Two
      metabolites as degradation intermediates with nitrite release into the medium,
      2,4-dinitrotoluene (2,4-DNT) and 4-aminodinitrotoluene (4-ADNT), were elucidated
      by thin layer chromatography (TLC) and gas chromatography-mass spectrometry (GC
      MS). These findings clearly indicate that Pseudomonas aeruginosa can be used in
      bioremediation of TNT contaminated sites. 

PMID- 26221095
TI  - A high-throughput screening assay for distinguishing nitrile hydratases from
      nitrilases.
AB  - A modified colorimetric high-throughput screen based on pH changes combined with
      an amidase inhibitor capable of distinguishing between nitrilases and nitrile
      hydratases. This enzymatic screening is based on a binary response and is
      suitable for the first step of hierarchical screening projects. 

PMID- 26221096
TI  - Clinical significance of the isolation of Candida species from hospitalized
      patients.
AB  - In this study, we isolated and phenotypically identified 108 yeast strains from
      various clinical specimens collected from 100 hospitalized patients at three
      tertiary hospitals in Sao Luis-Maranhao, Brazil, from July to December 2010. The
      isolates were analyzed for their susceptibility to four of the most widely used
      antifungal agents in the surveyed hospitals, amphotericin B, fluconazole, 5
      flucytosine and voriconazole. The species identified were Candida albicans
      (41.4%), Candida tropicalis (30.1%), C. glabrata (7.4%), Candida parapsilosis
      (5.5%), Candida krusei (4.6%), Cryptococcus neoformans (4.6%), Trichosporon spp .
      (3.7%), Candida norvegensis (0.9%), Rhodotorula glutinis (0.9%) and Pichia
      farinosa (0.9%). A higher isolation rate was observed in the following clinical
      specimens: urine (54 isolates; 50%), respiratory tract samples (21 isolates;
      19.4%) and blood (20 isolates; 18.6%). Candida albicans isolates were 100%
      sensitive to all antifungal agents tested, whereas Candida krusei and Crytococcus
      neoformans displayed intermediate resistance to 5-flucytosine, with Minimal
      Inhibitory Concentration (MIC) values of 8 mg/mL and 16 mg/mL, respectively. Both
      strains were also S-DD to fluconazole with an MIC of 16 mg/mL. C. tropicalis was
      resistant to 5-flucytosine with an MIC of 32 MUg/mL. This study demonstrates the
      importance of identifying the yeast species involved in community and nosocomial
      infections. 

PMID- 26221097
TI  - Synergistic effects of tacrolimus and azole antifungal compounds in fluconazole
      susceptible and fluconazole-resistant Candida glabrata isolates.
AB  - In vitro interaction between tacrolimus (FK506) and four azoles (fluconazole,
      ketoconazole, itraconazole and voriconazole) against thirty clinical isolates of
      both fluconazole susceptible and -resistant Candida glabrata were evaluated by
      the checkerboard microdilution method. Synergistic, indifferent or antagonism
      interactions were found for combinations of the antifungal agents and FK506. A
      larger synergistic effect was observed for the combinations of FK506 with
      itraconazole and voriconazole (43%), followed by that of the combination with
      ketoconazole (37%), against fluconazole-susceptible isolates. For fluconazole
      resistant C. glabrata , a higher synergistic effect was obtained from FK506
      combined with ketoconazole (77%), itraconazole (73%), voriconazole (63%) and
      fluconazole (60%). The synergisms that we observed in vitro , notably against
      fluconazole-resistant C. glabrata isolates, are promising and warrant further
      analysis of their applications in experimental in vivo studies. 

PMID- 26221098
TI  - Adherence and virulence genes of Escherichia coli from children diarrhoea in the
      Brazilian Amazon.
AB  - The bacterial pathogen most commonly associated with endemic forms of childhood
      diarrhoea is Escherichia coli . Studies of epidemiological characteristics of HEp
      2 cell-adherent E. coli in diarrhoeal disease are required, particularly in
      developing countries. The aim of this study was evaluate the presence and
      significance of adherent Escherichia coli from diarrhoeal disease in children.
      The prevalence of LA, AA, and DA adherence patterns were determined in HEp-2
      cells, the presence of virulence genes and the presence of the O serogroups in
      samples obtained from 470 children with acute diarrhoea and 407 controls in Porto
      Velho, Rondonia, Brazil. E. coli isolates were identified by PCR specific for
      groups of adherent E. coli . Out of 1,156 isolates obtained, 128 (11.0%) were
      positive for eae genes corresponding to EPEC, however only 38 (29.6%) of these
      amplified bfpA gene . EAEC were isolated from 164 (14.1%) samples; of those
      41(25%), 32 (19%) and 16 (9.7%) amplified eagg , aggA or aafA genes, respectively
      and aggA was significantly associated with diarrhoea ( P = 0.00006). DAEC
      identified by their adhesion pattern and there were few isolates. In conclusion,
      EAEC was the main cause of diarrhoea in children, especially when the aggA gene
      was present, followed by EPEC and with a negligible presence of DAEC. 

PMID- 26221099
TI  - Evaluation of some pharmacological activities of Budmunchiamine - A isolated from
      Albizia amara.
AB  - The present investigations were aimed to evaluate the antimicrobial and
      antioxidant efficacies of budmunchiamine-A (BUA) of Albizia amara . The activity
      guided isolation leaded to isolate the bioactive compound budmunchiamine-A from
      alkaloid extract of A. amara . The budmunchiamine-A showed significant broad
      spectrum antimicrobial activity with zone of inhibition (ZOI), minimum inhibitory
      concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC)
      values varied from 7.3 to 24.5 mm, 0.95 to 62.5 MUg/mL, and 1.9 to 250 MUg/mL,
      respectively. The budmunchiamine-A exhibited moderate antioxidant activity with
      inhibitory concentration 50% (IC 50 ) value of 400 MUg/mL in 2,2-diphenyl-1
      picrylhydrazyl (DPPH) assay and percent inhibition of beta-carotene/linoleic acid
      was 67.8%. The results suggest the possible use of budmunchiamine-A as a
      molecular entity for drug development in pharmaceutical industry.

PMID- 26221100
TI  - Arcobacter butzleri and A. cryaerophilus in human, animals and food sources, in
      southern Chile.
AB  - The isolation frequency of Arcobacter species in children with diarrhea, fowls,
      mammals and food of avian and marine origin was established. In all the samples
      it was possible to isolate Arcobacter species corresponding 201 (39.4%) to A.
      butzleri and 24 (4.7) to A. cryaerophilus . Both species were simultaneously
      isolated in 19 (3.7%) being A. butzleri the most frequently isolated species.

PMID- 26221101
TI  - Sub-MIC of antibiotics induced biofilm formation of Pseudomonas aeruginosa in the
      presence of chlorhexidine.
AB  - Public health is facing a new challenge due to the alarming increase in bacterial
      resistance to most of the conventional antibacterial agents. It has been found
      that only minor cell damage is caused when exposed to sub-lethal levels of
      antimicrobial. Biofilms can play an important role in producing resistance, which
      is developed to reservoirs of pathogens in the hospital and cannot be easily
      removed. The aim of this study was to test whether the sub-lethal dose of
      antibiotics can induce biofilm formation of P. aeruginosa following incubating in
      the presence and absence of chlorhexidine. Standard antibiotic-micro broth 96
      flat well plates were used for determination of MIC and biofilm assay. The
      adherence degree of biofilm was determined by estimation of OD 630 nm values
      using ELISA reader. The mean 22 isolates of P. aeruginosa growing in culture with
      presence and absence of chlorhexidine, could exhibited the significant (p <
      0.001) proportion of adherence followed incubation in sub minimal inhibitory
      concentrations (Sub-MIC) of cefotaxim, amoxicillin, and azithromycin in
      comparison with control (antibiotic-free broth), while the sub-MIC of
      ciprofloxacin revealed significant inhibition of biofilm. CONCLUSION: Incubating
      the isolates of P. aeruginosa to sub-MIC of antibiotics exhibited induction of
      biofilm in the presence of chlorhexidine.

PMID- 26221102
TI  - Occurrence of genes encoding enterotoxins in uropathogenic Escherichia coli
      isolates.
AB  - To determine the presence of some toxins of diarrheagenic Escherichia coli (DEC)
      in uropathogenic E. coli (UPEC), 138 urinary tract infection (UTI)-causing UPECs
      were analyzed. The astA , set , sen and cdtB genes were detected in 13 (9.4%), 2
      (1.3%), 13 (9.4%) and 0 (0%) of UPEC isolates respectively. The results show that
      some genes encoding toxins can be transferred from DEC pathotypes to UPECs
      therefore these isolates can transform into potential diarrhea-causing agents.

PMID- 26221103
TI  - Detection of both vanA & vanB genes in vanA phenotypes of Enterococci by Taq Man
      RT-PCR.
AB  - Twenty seven isolates of vancomycin resistant Enterococci based on the disk
      diffusion and E- test have been screened; being found eight (0.3%) clinical
      isolates of vanA & vanB through Taq Man Real Time PCR assay. This study shows the
      presence of both vanA & vanB genotypes in vanA phenotypes clinical isolates in
      the three hospitals in Iran.

PMID- 26221104
TI  - Adhesion, biofilm and genotypic characteristics of antimicrobial resistant
      Escherichia coli isolates.
AB  - Aggregative adherence to human epithelial cells, most to renal proximal tubular
      (HK-2) cells, and biofilm formation was identified among antimicrobial resistant
      Escherichia coli strains mainly isolated from bacteremia. The importance of these
      virulence properties contributing to host colonization and infection associated
      with multiresistant E. coli should not be neglected. 

PMID- 26221105
TI  - Characterization of the spoilage lactic acid bacteria in "sliced vacuum-packed
      cooked ham".
AB  - The lactic acid bacteria are involved with food fermentation and in such cases
      with food spoilage. Considering the need to reduce the lactic acid bacteria
      growth in meat products, the aim of this work was to enumerated and investigated
      the lactic acid bacteria present on sliced vacuum-packed cooked ham stored at 4 
      degrees C and 8  degrees C for 45 days by phenotypic and molecular techniques.
      The quantification showed that the lactic acid bacteria were present from the
      first day with mean count of 1.98 log cfu/g for the four batches analyzed. The
      lactic acid bacteria grew rapidly on the samples, and plate counts around 7.59
      log cfu/g and 8.25 log cfu/g were detected after 45 days of storage at 4  degrees
      C and 8  degrees C, respectively; storage temperatures studied showed significant
      influence on the microorganism in study growth. The predominant lactic acid
      bacteria associated with the spoilage samples at one day of storage includes
      Lactobacillus sp., the phenotypic overlap Leuconostoc / Weissella sp. and
      Enterococcus sp. At 45 days of storage at 4 and 8  degrees C the mainly specie
      was Lactobacillus curvatus , following by Lactobacillus sakei and Leuconostoc
      mesentereoides ; the Enterococcus sp. was not present in the samples.

PMID- 26221106
TI  - Binding effect of proline-rich-proteins (PRPs) on in vitro antimicrobial activity
      of the flavonoids.
AB  - The interaction of the cyanidin, pelargonidin, catechin, myrecetin and kaempferol
      with casein and gelatin, as proline rich proteins (PRPs), was studied. The
      binding constants calculated for both flavonoid-casein and flavonoid-gelatin were
      fairly large (10 (5) -10 (7) M (-1) ) indicating strong interaction. Due to
      higher proline content in gelatin, the binding constants of flavonoid-gelatin
      (2.5 * 10 (5) -6.2 * 10 (7) M (-1) ) were found to be higher than flavonoid
      casein (1.2 * 10 (5) -5.0 * 10 (7) M (-1) ). All the flavonoids showed
      significant antibacterial activity against the tested strains. Significant loss
      in activity was observed due to the complexation with PRPs confirming that
      binding effectively reduced the concentration of the free flavonoids to be
      available for antibacterial activity. The decline in activity was corresponding
      to the values of the binding constants. Though the activities of free catechin
      and myrecetin were higher compared to pelargonidin, cyanidin and kaempferol yet
      the decline in activity of catechin and myrecetin due to complexation with casein
      and gelatin was more pronounced. 

PMID- 26221107
TI  - Biological activity of the essential oils from Cinnamodendron dinisii and
      Siparuna guianensis.
AB  - This study had analyzed the antibacterial, antifungal and trypanocidal activity
      of the essential oils from Cinnamodendron dinisii Schwacke (Canellaceae) and
      Siparuna guianensis Aublet (Siparunaceae). The essential oils were obtained from
      fresh leaves by hydrodistillation, using a modified Clevenger apparatus. Chemical
      analysis by gas-liquid chromatography coupled to mass spectrometry (GC-MS) showed
      that these essential oils are rich in monoterpene and sesquiterpene hydrocarbons.
      Activity against the pathogenic bacteria Escherichia coli , Listeria
      monocytogenes , Pseudomonas aeruginosa , Salmonella choleraesuis and
      Staphylococcus aureus was evaluated with the agar cavity diffusion method, while
      activity on the filamentous fungi Aspergillus flavus , Aspergillus niger ,
      Aspergillus carbonarius and Penicillium commune was evaluated by the disk
      diffusion technique. Trypanocidal activity was tested against Trypanosoma cruzi
      epimastigotes, using the Tetrazolium salt (MTT) colorimetric assay. Both
      essential oils exhibited low inhibitory effect towards bacteria, showing high MIC
      values (125-500 MUg mL (-1) ), with Gram positive bacteria being more
      susceptible. Better inhibitory effect was obtained for the evaluated fungi, with
      lower MIC values (7.81-250 MUg mL (-1) ), being A. flavus the most susceptible
      species. Both essential oils presented low trypanocidal activity, with IC 50 /24
      h values of 209.30 MUg mL (-1) for S. guianensis and 282.93 MUg mL (-1) for C.
      dinisii . Thus, the high values observed for the MIC of evaluated bacteria and
      for IC 50 /24 h of T. cruzi , suggest that the essential oils have a low
      inhibitory activity against these microorganisms. In addition, the low MIC values
      observed for the tested fungi species indicate good inhibitory activity on these
      microorganisms's growth.

PMID- 26221108
TI  - Iron bioaccumulation in mycelium of Pleurotus ostreatus.
AB  - Pleurotus ostreatus is able to bioaccumulate several metals in its cell
      structures; however, there are no reports on its capacity to bioaccumulate iron.
      The objective of this study was to evaluate cultivation variables to increase
      iron bioaccumulation in P. ostreatus mycelium. A full factorial design and a
      central composite design were utilized to evaluate the effect of the following
      variables: nitrogen and carbon sources, pH and iron concentration in the solid
      culture medium to produce iron bioaccumulated in mycelial biomass. The maximum
      production of P. ostreatus mycelial biomass was obtained with yeast extract at
      2.96 g of nitrogen L (-1) and glucose at 28.45 g L (-1) . The most important
      variable to bioaccumulation was the iron concentration in the cultivation medium.
      Iron concentration at 175 mg L (-1) or higher in the culture medium strongly
      inhibits the mycelial growth. The highest iron concentration in the mycelium was
      3500 mg kg (-1) produced with iron addition of 300 mg L (-1) . The highest iron
      bioaccumulation in the mycelium was obtained in culture medium with 150 mg L (-1)
      of iron. Iron bioaccumulation in P. ostreatus mycelium is a potential alternative
      to produce non-animal food sources of iron. 

PMID- 26221109
TI  - Bacteriocinogenic Lactococcus lactis subsp. lactis DF04Mi isolated from goat
      milk: Application in the control of Listeria monocytogenes in fresh Minas-type
      goat cheese.
AB  - Listeria monocytogenes is a pathogen frequently found in dairy products. Its
      control in fresh cheeses is difficult, due to the psychrotrophic properties and
      salt tolerance. Bacteriocinogenic lactic acid bacteria (LAB) with proven in vitro
      antilisterial activity can be an innovative technological approach but their
      application needs to be evaluated by means of in situ tests. In this study, a
      novel bacteriocinogenic Lactococcus lactis strain ( Lc . lactis DF4Mi), isolated
      from raw goat milk, was tested for control of growth of L. monocytogenes in
      artificially contaminated fresh Minas type goat cheese during storage under
      refrigeration. A bacteriostatic effect was achieved, and counts after 10 days
      were 3 log lower than in control cheeses with no added LAB. However, this effect
      did not differ significantly from that obtained with a non-bacteriocinogenic Lc.
      lactis strain. Addition of nisin (12.5 mg/kg) caused a rapid decrease in the
      number of viable L. monocytogenes in the cheeses, suggesting that further studies
      with the purified bacteriocin DF4Mi may open new possibilities for this strain as
      biopreservative in dairy products. 

PMID- 26221110
TI  - Milk-deteriorating exoenzymes from Pseudomonas fluorescens 041 isolated from
      refrigerated raw milk.
AB  - The practice of refrigerating raw milk at the farm has provided a selective
      advantage for psychrotrophic bacteria that produce heat-stable proteases and
      lipases causing severe quality problems to the dairy industry. In this work, a
      protease (AprX) and a lipase (LipM) produced by Pseudomonas fluorescens 041, a
      highly proteolytic and lipolytic strain isolated from raw milk obtained from a
      Brazilian farm, have been purified and characterized. Both enzymes were purified
      as recombinant proteins from Escherichia coli . The AprX metalloprotease
      exhibited activity in a broad temperature range, including refrigeration, with a
      maximum activity at 37  degrees C. It was active in a pH range of 4.0 to 9.0.
      This protease had maximum activity with the substrates casein and gelatin in the
      presence of Ca (+2) . The LipM lipase had a maximum activity at 25  degrees C and
      a broad pH optimum ranging from 7.0 to 10. It exhibited the highest activity, in
      the presence of Ca (+2) , on substrates with long-chain fatty acid residues.
      These results confirm the spoilage potential of strain 041 in milk due to, at
      least in part, these two enzymes. The work highlights the importance of studies
      of this kind with strains isolated in Brazil, which has a recent history on the
      implementation of the cold chain at the dairy farm.

PMID- 26221111
TI  - Determining the minimum ripening time of artisanal Minas cheese, a traditional
      Brazilian cheese.
AB  - Physical, physicochemical, and microbiological changes were monitored in 256
      samples of artisanal Minas cheese from eight producers from Serro region (Minas
      Gerais, Brazil) for 64 days of ripening to determine the minimum ripening time
      for the cheese to reach the safe microbiological limits established by Brazilian
      legislation. The cheeses were produced between dry season (April-September) and
      rainy season (October-March); 128 cheeses were ripened at room temperature (25 +/
      4  degrees C), and 128 were ripened under refrigeration (8 +/- 1  degrees C), as
      a control. No Listeria monocytogenes was found, but one cheese under
      refrigeration had Salmonella at first 15 days of ripening. However, after 22
      days, the pathogen was not detected. Seventeen days was the minimum ripening time
      at room temperature to reduce at safe limits of total coliforms > 1000 cfu.g (-1)
      ), Escherichia coli and Staphylococcus aureus (> 100 cfu.g (-1) ) in both periods
      of manufacture. Otherwise under refrigeration, as expected, the minimum ripening
      time was longer, 33 days in the dry season and 63 days in the rainy season. To
      sum up, we suggest that the ripening of artisanal Minas cheese be done at room
      temperature, since this condition shortens the time needed to reach the
      microbiological quality that falls within the safety parameters required by
      Brazilian law, and at the same time maintain the appearance and flavor
      characteristics of this traditional cheese. 

PMID- 26221112
TI  - Different methods to quantify Listeria monocytogenes biofilms cells showed
      different profile in their viability.
AB  - Listeria monocytogenes is a foodborne pathogen able to adhere and to form
      biofilms in several materials commonly present in food processing plants. The aim
      of this study was to evaluate the resistance of Listeria monocytogenes attached
      to abiotic surface, after treatment with sanitizers, by culture method,
      microscopy and Quantitative Real Time Polymerase Chain Reaction (qPCR). Biofilms
      of L. monocytogenes were obtained in stainless steel coupons immersed in Brain
      Heart Infusion Broth, under agitation at 37  degrees C for 24 h. The methods
      selected for this study were based on plate count, microscopic count with the aid
      of viability dyes (CTC-DAPI), and qPCR. Results of culture method showed that
      peroxyacetic acid was efficient to kill sessile L. monocytogenes populations,
      while sodium hypochlorite was only partially effective to kill attached L.
      monocytogenes (p < 0.05). When, viability dyes (CTC/DAPI) combined with
      fluorescence microscopy and qPCR were used and lower counts were found after
      treatments (p < 0.05). Selective quantification of viable cells of L.
      monocytogenes by qPCR using EMA revelead that the pre-treatment with EMA was not
      appropriate since it also inhibited amplification of DNA from live cells by ca. 2
      log. Thus, the use of CTC counts was the best method to count viable cells in
      biofilms. 

PMID- 26221113
TI  - Safety, beneficial and technological properties of Enterococcus faecium isolated
      from Brazilian cheeses.
AB  - This study aimed to characterize the safety and technological properties of
      Enterococcus faecium strains isolated from Brazilian Coalho cheeses. High levels
      of co-aggregation were observed between Enterococcus faecium strains EM485 and
      EM925 and both Escherichia coli and Clostridium perfringens . Both strains
      presented low levels of hydrophobicity. E. faecium EM485 and EM925 were both able
      to grow in the presence of 0.5% of the sodium salts of taurocholic acid (TC),
      taurodeoxycholic acid (TDC), glycocholic acid (GC), and glycodeoxycholic acid
      (GDC), although they showed the ability to deconjugate only GDC and TDC. Both
      strains showed good survival when exposed to conditions simulating the gastro
      intestinal tract (GIT). When tested for the presence of virulence genes, only
      tyrosine decarboxylase and vancomycin B generated positive PCR results.

PMID- 26221114
TI  - Isolation of a thermostable acid phytase from Aspergillus niger UFV-1 with strong
      proteolysis resistance.
AB  - An Aspergillus niger UFV-1 phytase was characterized and made available for
      industrial application. The enzyme was purified via ultrafiltration followed by
      acid precipitation, ion exchange and gel filtration chromatography. This protein
      exhibited a molecular mass of 161 kDa in gel filtration and 81 kDa in sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), indicating that it
      may be a dimer. It presented an optimum temperature of 60  degrees C and optimum
      pH of 2.0. The K M for sodium phytate hydrolysis was 30.9 mM, while the k cat and
      k cat / K M were 1.46 *10 (5) s (-1) and 4.7 * 10 (6) s (-1) .M (-1) ,
      respectively. The purified phytase exhibited broad specificity on a range of
      phosphorylated compounds, presenting activity on sodium phytate, p-NPP, 2-
      naphthylphosphate, 1- naphthylphosphate, ATP, phenyl-phosphate, glucose-6
      phosphate, calcium phytate and other substrates. Enzymatic activity was slightly
      inhibited by Mg (2+) , Cd (2+) , K (+) and Ca (2+) , and it was drastically
      inhibited by F (-) . The enzyme displayed high thermostability, retaining more
      than 90% activity at 60  degrees C during 120 h and displayed a t 1/2 of 94.5 h
      and 6.2 h at 70  degrees C and 80  degrees C, respectively. The enzyme
      demonstrated strong resistance toward pepsin and trypsin, and it retained more
      than 90% residual activity for both enzymes after 1 h treatment. Additionally,
      the enzyme efficiently hydrolyzed phytate in livestock feed, liberating 15.3
      MUmol phosphate/mL after 2.5 h of treatment. 

PMID- 26221115
TI  - Hydroxylation of 1,8-cineole by Mucor ramannianus and Aspergillus niger.
AB  - The monoterpenoid 1,8-cineole is obtained from the leaves of Eucalyptus globulus
      and it has important biological activities. It is a cheap natural substrate
      because it is a by-product of the Eucalyptus cultivation for wood and pulp
      production. In this study, it was evaluated the potential of three filamentous
      fungi in the biotransformation of 1,8-cineole. The study was divided in two
      steps: first, reactions were carried out with 1,8-cineole at 1 g/L for 24 h;
      afterwards, reactions were carried out with substrate at 5 g/L for 5 days. The
      substrate was hydroxylated into 2-exo-hydroxy-1,8-cineole and 3-exo-hydroxy-1,8
      cineole by fungi Mucor ramannianus and Aspergillus niger with high
      stereoselectivity. Trichoderma harzianum was also tested but no transformation
      was detected. M. ramannianus led to higher than 99% of conversion within 24 h
      with a starting high substrate concentration (1 g/L). When substrate was added at
      5 g/L, only M. ramannianus was able to catalyze the reaction, but the conversion
      level was 21.7% after 5 days. Both products have defined stereochemistry and
      could be used as chiral synthons. Furthermore, biological activity has been
      described for 3-exo-hydroxy-1,8-cineol. To the best of our knowledge, this is the
      first report on the use of M. ramannianus in this reaction. 

PMID- 26221116
TI  - Different resistance patterns of reference and field strains of Brucella abortus.
AB  - The aim of this study was to evaluate the growth of the B. abortus reference
      strains and field isolates on media containing different inhibitor agents.
      Reference strains were seeded on tryptose agar containing: i-erythritol (1.0
      mg/mL), fuchsin (20 MUg/mL and 80 MUg/mL), thionin (2.5 MUg/mL and 10 MUg/mL),
      rifampicin (200 MUg/mL) and safranin O (200 MUg/mL). Field isolates were tested
      only on media containing i-erythritol, rifampicin and thionin. Furthermore, each
      suspension was also inoculated on tryptose agar incubated in air, to test its
      ability to grow without CO 2 . Sensitivity to fuchsin was similar among reference
      strains evaluated. Growth of S19, 544 and 2308 but not RB51 were inhibited on
      media containing rifampicin. Medium with safranin O showed no inhibition for
      RB51, 544 and 2308, but it partially inhibited the S19 growth as well as medium
      containing i-erythritol. Treatment/control growth ratio for 2308 on tryptose agar
      containing thionin (2.5 MUg/mL) was approximatelly 1.0, whereas S19 and RB51
      showed 0.85 and 0.89 ratios, respectively. Growth of 544, S19 and RB51 but not
      2308 was completely inhibited on medium with thionin (10 MUg/mL). All field
      strains grew on medium containing i-erythritol, but were completelly inhibited by
      rifampicin. With exception of A1 ( B. abortus biovar 3) all field isolates grew
      on medium with thionin, although some strains showed a treatment/control growth
      ratio of 0.75-0.80 (10 MUg/mL). These results showed that tryptose agar with
      thionin, i-erythritol or rifampicin could be useful for differentiating vaccine,
      challenge and field strains of B. abortus.

PMID- 26221117
TI  - Antimicrobial resistance and virulence gene profiles in P. multocida strains
      isolated from cats.
AB  - Cats are often described as carriers of Pasteurella multocida in their oral
      microbiota. This agent is thought to cause pneumonia, conjunctivitis, rhinitis,
      gingivostomatitis, abscess and osteonecrosis in cats. Human infection with P.
      multocida has been described in several cases affecting cat owners or after cat
      bites. In Brazil, the cat population is approximately 21 million animals and is
      increasing, but there are no studies of the presence of P. multocida in the
      feline population or of human cases of infection associated with cats. In this
      study, one hundred and ninety-one healthy cats from owners and shelters in Sao
      Paulo State, Brazil, were evaluated for the presence of P. multocida in their
      oral cavities. Twenty animals were positive for P. multocida , and forty-one
      strains were selected and characterized by means of biochemical tests and PCR.
      The P. multocida strains were tested for capsular type, virulence genes and
      resistance profile. A total of 75.6% (31/41) of isolates belonged to capsular
      type A, and 24.4% (10/41) of the isolates were untypeable. None of the strains
      harboured toxA, tbpA or pfhA genes. The frequencies of the other genes tested
      were variable, and the data generated were used to build a dendrogram showing the
      relatedness of strains, which were clustered according to origin. The most common
      resistance profile observed was against sulfizoxazole and trimethoprim
      sulphamethoxazole. 

PMID- 26221118
TI  - Bovine Herpesvirus 4 in Parana State, Brazil: case report, viral isolation, and
      molecular identification.
AB  - Bovine Herpesvirus 4 (BoHV-4) is a member of Gammaherpesvirinae sub-family and
      belongs to genus Rhadinovirus . This virus has been associated with different
      clinical manifestations and research activity has put forward a strong
      correlation among virus infection, postpartum metritis, and abortion. The goal of
      this work was to characterize a virus strain isolate from a cow's uterine
      outflow. From swabs drawn of uterine secretion, a virus strain was isolated and
      characterized by its cytopathology, morphology, and molecular biology approaches.
      In culture there was CPE development, characterized mainly by long strands with
      several small balloons along them, radiated from infected cells. Electron
      microscopy analysis revealed virus particles that had icosahedrical capsid
      symmetry surrounded by a loose envelope, typical of a herpesvirus. A 2,571 bp PCR
      product after Hind III digestion generated four fragments, whose base pair
      composition were 403, 420, 535, and 1,125 bp. Restriction enzymes Hind III and
      Bam HI generated the expected diagnostic bands as well as a 2,350 bp hypermolar
      fragment as a result of Bam HI treatment to demonstrate that agent was a bovine
      herpesvirus 4, appertaining to DN-599 group. 

PMID- 26221119
TI  - Copper induction and differential expression of laccase in Aspergillus flavus.
AB  - Aspergillus flavus was isolated from soil and exhibited laccase activity under
      both constitutive and copper induced conditions. Spiking the medium with 1 mM
      copper sulfate resulted in an increase in the activity which reached 51.84 U/mL,
      a distinctive protein band was detected at 60 kDa. The extracellular enzyme was
      purified 81 fold using gel filtration chromatography and resulted in two
      different laccase fractions L1 and L2, the latter had a higher enzymatic activity
      which reached 79.57 U/mL and specific activity of 64.17 U/MUg protein. The
      analysis of the spectrum of the L2 fraction showed a shoulder at 330 nm which is
      characteristic for T2/T3 copper centers; both copper and zinc were detected
      suggesting that this is an unconventional white laccase. Primers of laccase gene
      were designed and synthesized to recover specific gene from A. flavus . Sequence
      analysis indicated putative laccase (Genbank ID: JF683612) at the amino acid
      level suggesting a close identity to laccases from other genera containing the
      copper binding site. Decolorization of textile waste water under different
      conditions showed possible application in bioremediation within a short period of
      time. The effect of copper on A. flavus was concentration dependent. 

PMID- 26221120
TI  - Effect of fungicide on Fusarium verticillioides mycelial morphology and fumonisin
      B1 production.
AB  - The effect of fludioxonil + metalaxyl-M on the mycelial morphology, sporulation
      and fumonisin B 1 production by Fusarium verticillioides 103 F was evaluated.
      Scanning electron microscopy analysis showed that the fungicide caused inhibition
      of hyphal growth and defects on hyphae morphology such as cell wall disruption,
      withered hyphae, and excessive septation. In addition, extracellular material
      around the hyphae was rarely observed in the presence of fludioxonil + metalaxyl
      M. While promoting the reduction of mycelial growth, the fungicide increased
      sporulation of F. verticillioides compared to the control, and the highest
      production occurred on the 14 (th) day in the treatments and on the 10 (th) day
      in the control cultures. Fumonisin B 1 production in the culture media containing
      the fungicide (treatment) was detected from the 7 (th) day incubation, whereas in
      cultures without fungicide (control) it was detected on the 10 (th) day. The
      highest fumonisin B 1 production occurred on the 14 (th) day, both for the
      control and for the treatment. Fludioxonil + metalaxyl - M can interfere in F.
      verticillioides mycelial morphology and sporulation and increase fumonisin B 1
      levels. These data indicate the importance of understanding the effects of
      fungicide to minimize the occurrence of toxigenic fungi and fumonisins. 

PMID- 26221121
TI  - Epidemiology of oral HPV in the oral mucosa in women without signs of oral
      disease from Yucatan, Mexico.
AB  - High-risk human papillomaviruses (HR-HPV) are considered necessary for the
      development of cervical cancer. Furthermore, there is no doubt that some types of
      oral squamous cell carcinoma are associated with HR-HPV. The epidemiology of oral
      HPV infections in healthy subjects remains unclear due to a lack of knowledge.
      The objective of this study was to investigate the epidemiology of human
      papillomavirus infections of the oral mucosa without pathology. A cross-sectional
      study was performed; samples from 390 women seeking prenatal care, Pap smears,
      family planning or gynecological diseases were studied. Oral cells were collected
      by direct swab sampling. Information regarding sociodemographic status, sexual
      behavior, infectious diseases, contraceptive history and tobacco and alcohol
      consumption were obtained through direct interviews. HPV and genotypes were
      detected by type-specific polymerase chain reaction. Our results revealed that
      14% of the women studied had an oral HPV infection. Women <= 20 years of age had
      the highest HPV prevalence (24.5%). In total, seven genotypes were identified,
      including the high-risk genotypes 16, 18, 58 and 59 and the low-risk genotypes 6,
      81 and 13, the latter of which is a type exclusive to oral mucosa. Sexual
      behavior was not associated with the presence of genital HPV types in the oral
      mucosa. Genital HPV types were present in the oral mucosa of women without
      associated clinical manifestations; however, sexual behavior was not associated
      with infection, and therefore others routes of transmission should be explored. 

PMID- 26221122
TI  - Torque teno virus among dialysis and renal-transplant patients.
AB  - Patients who undergo dialysis treatment or a renal transplant have a high risk of
      blood-borne viral infections, including the Torque teno virus (TTV). This study
      identified the presence of TTV and its genome groups in blood samples from 118
      patients in dialysis and 50 renal-transplant recipients. The research was
      conducted in a hospital in the city of Maringa, state of Parana. The viral DNA,
      obtained from whole blood, was identified by using two nested Polymerase Chain
      Reactions (PCR). The frequencies of TTV were 17% and 36% in dialysis patients
      using the methodology proposed by Nishizawa et al . (1997) and Devalle and Niel
      (2004) , respectively, and 10% and 54% among renal-transplant patients. There was
      no statistically significant association between the frequency of the pathogen
      and the variables: gender, time in dialysis, time since transplant, blood
      transfusions, and the concomitant presence of hepatitis B, for either the
      dialysis patients or the renal-transplant recipients. Among dialysis patients and
      renal-transplant recipients, genogroup 5 was predominant (48% and 66%
      respectively), followed by genogroup 4 (37% and 48%) and genogroup 1 (23% and
      25%). Genogroup 2 was present in both groups of patients. Some patients had
      several genogroups, but 46% of the dialysis patients and 51% of the renal
      transplant recipients had only a single genogroup. This study showed a high
      prevalence of TTV in dialysis patients and renal-transplant recipients. 

PMID- 26221123
TI  - Tissue apoptosis in mice infected with Leptospira interrogans serovar
      Icterohaemorrhagiae.
AB  - BACKGROUND: This investigation aimed to evaluate the occurrence of some apoptotic
      features induced by Leptospira interrogans serovar Icterohaemorrhagiae infection
      in young BALB/c mice during 2, 4, 7, 10, 14 and 21 days post-infection (dpi).
      METHODS: The animals were euthanized and lung, liver and kidneys were harvested
      to histopathology analysis and immunohistochemistry to caspase-3 antigen
      detection was performed. RESULTS: Chromatin condensation in kidney and liver
      tissues, but not in lung tissue, was observed. Caspase-3 reactive cells, mainly
      characterized as renal epithelial cells, were detected in the days 14 and 21 at
      high levels when compared to days 2, 4 and 7 (p = 0.025; p < 0.05). Lung sections
      revealed caspase-3 labeled alveolar cells in 10 and 14 days post-infection was
      higher than observed at 7 days (p = 0.0497; p < 0.05). Liver sections
      demonstrated reactive cells at a highest level at 14 and 21 days post-infection
      when comparison to 2, 4, 7 and 10 days (p = 0.0069; p < 0.05). CONCLUSIONS: Our
      results suggest that infection of L. interrogans induce in kidney, liver and lung
      an activation of apoptosis mediated by caspase-3 dependent pathway in later
      phases of infectious process.

PMID- 26221125
TI  - DNA flow cytometric analysis in variable types of hydropic placentas.
AB  - BACKGROUND: Differential diagnosis between complete hydatidiform mole, partial
      hydatidiform mole and hydropic abortion, known as hydropic placentas is still a
      challenge for pathologists but it is very important for patient management.
      OBJECTIVE: We analyzed the nuclear DNA content of various types of hydropic
      placentas by flowcytometry. MATERIALS AND METHODS: DNA ploidy analysis was
      performed in 20 non-molar (hydropic and non-hydropic spontaneous abortions) and
      20 molar (complete and partial moles), formalin-fixed, paraffin-embedded tissue
      samples by flow cytometry. The criteria for selection were based on the
      histopathologic diagnosis. RESULTS: Of 10 cases histologically diagnosed as
      complete hydatiform mole, 9 cases yielded diploid histograms, and 1 case was
      tetraploid. Of 10 partial hydatidiform moles, 8 were triploid and 2 were diploid.
      All of 20 cases diagnosed as spontaneous abortions (hydropic and non-hydropic)
      yielded diploid histograms. CONCLUSION: These findings signify the importance of
      the combined use of conventional histology and ploidy analysis in the
      differential diagnosis of complete hydatidiform mole, partial hydatidiform mole
      and hydropic abortion.

PMID- 26221124
TI  - The imbalance in expression of angiogenic and anti-angiogenic factors as
      candidate predictive biomarker in preeclampsia.
AB  - Preeclampsia is an important pregnancy disorder with serious maternal and fetal
      complications which its etiology has not been completely understood yet. Early
      diagnosis and management of disease could reduce its potential side effects. The
      vascular endothelial growth factor (VEGF) family including VEGF-A is the most
      potent endothelial growth factor which induces angiogenesis and endothelial cell
      proliferation and has basic role in vasculogenesis. VEGF and its tyrosine kinase
      receptors (Flt1 and KDR) are major factors for fetal and placental angiogenic
      development. Finding mechanisms involved in expression of angiogenic factors may
      lead to new prognostic and therapeutic points in management of preeclampsia.
      Recent researches, has shown capability of some anti-angiogenic factors as
      potential candidate to be used as early predictors for preeclampsia. Soluble fms
      like tyrosin kinase-1 (sFlt1) is a truncated splice variant of the membrane-bound
      VEGF receptor Flt1, that is produced by the placenta and it can bind to
      angiogenic growth factors and neutraliz, their effects. It is also observed that
      the ratio of sFlt1 to placental growth factor is valuable as prognostic marker.
      In this review, VEGF family member's role in angiogenesis is evaluated as
      biomarkers to be used for prediction of preeclampsia. 

PMID- 26221126
TI  - Impact of morphine dependency and detoxification by methadone on male's rat
      reproductive system.
AB  - BACKGROUND: One of the problems that addicts suffer from is decreased libido.
      Erectile dysfunction has been reported in men using opioids for treatment of
      heroin addiction. OBJECTIVE: The study was performed to investigate the effects
      of morphine and detoxification with methadone as causes of sexual dysfunction in
      addiction. METHODS AND METHODS: A total of 40 adult male rats (Wistar) were used.
      Animals were divided in to 4 groups. Control groups received saline for 30 days.
      Other 2 groups received 10 mg/kg morphine on day 1 and the morphine doses
      increased daily by 2 mg/kg increments per day until in day 30 a maximum of 68
      mg/kg twice daily was achieved. Withdrawal syndrome sings were evaluated. At the
      end of period, one group of 2 morphine dependent groups was treated with
      methadone during 14 days. Animals in group 4 (saline solution+ methadone)
      received saline for 30 consecutive days and then detoxified with methadone during
      14 days. Partial weights of seminal vesicles, testes, prostates, seminal vesicles
      content, concentrations of luteinizing hormone, follicle stimulating hormone, and
      testosterone in serum were determined. RESULTS: In the dependent group serum
      levels of testosterone (p<0.001), folicle stimulating hormone (p=0.0097) and
      luteinizing hormone (p=0.0031) as well as the weights of testes (p=0.0051),
      partial weights of prostates, seminal vesicles and seminal vesicles contents
      (p<0.001) were reduced as compared with control group. In the morphine dependent
      animals detoxified with methadone, testosterone concentrations and seminal
      vesicles contents remained lower than levels in the control group (p<0.001).
      CONCLUSION: The results suggest that morphine dependence may impair the
      reproductive function in male rats.

PMID- 26221127
TI  - Oxytocin can decrease germ cells apoptotic index in testis under acute ischemia
      reperfusion in a rat model.
AB  - Ischemia reperfusion (IR) is the main pathology of torsion of testis and it is a
      common urologic emergency. There is some evidence that shows oxytocin (OT) plays
      role in ischemia reperfusion. OBJECTIVE: To evaluate this hypothesis that OT can
      decrease germ cell apoptotic index in testis under acute ischemia reperfusion in
      a rat model. MATERIALS AND METHODS: 20 adult rats were randomly divided into four
      groups: Control, IR, OT and IR+ OT (OTA). Testicular ischemia was achieved by 720
      degrees  torsion of the left testis for 2 hr. Then, torsion was removed and
      reperfusion was performed. Immediately after induction of reperfusion 0.03 ug/kg
      OT were administered intraperitoneally to the IR+ OT. Three hours after surgery
      left testis was removed and evaluations were made by Johnson's score, ELISA,
      immunohistochemistry and histomorphometry for study of maturity of
      spermatogenesis, endocrine profiles, apoptosis and quantitative studies,
      respectively. RESULTS: The results showed in addition tissue edema and
      congestion, a significant reduced in Johnson's score were detected in IR group in
      comparison with controls (p=0.01), and apoptotic index increased significantly
      (p=0.001). Administration of OT in OT+IR group, increased Johnson's score but it
      was not statistically significant. Germinal epithelium thickness was increased
      significantly (p=0.03), although apoptotic index decreased significantly in
      comparison with the IR group (p=0.04). However there was not significant
      difference in serum levels of testosterone, FSH and LH in none of groups
      (p=0.07). CONCLUSION: These results suggested that OT can decrease apoptotic
      index and improves complication of acute ischemic reperfusion in testis in a rat
      model.

PMID- 26221128
TI  - Protective effects of ethyl pyruvate on sperm quality in cyclophosphamide treated
      mice.
AB  - BACKGROUND: One of the affecting factors in disturbance process of
      spermatogenesis is chemotherapeutic-induced oxidative stress resulted from
      cyclophosphamide (CP) treatment which leads to diminished sperm quality via
      interference in spermatogenesis process. OBJECTIVE: This study was conducted to
      investigate the effects of ethyl pyruvate (EP) in reducing the CP-induced side
      effects on reproductive system. MATERIALS AND METHODS: 24 mature male mice were
      randomly divided into 3 equal groups and were undergone therapy for 35 days.
      Control group received normal saline (0.1 ml/day, IP). CP group were injected CP
      (15 mg/kg/week, IP) and CP+EP group received EP (40 mg/kg/day, IP) as well as CP.
      In the end of the treatment period, the mice were euthanized by cervical
      dislocation. Then, the epididymis was incubated with CO2 in a human tubal fluid
      medium (1 ml) for half an hour in order to float sperm. Then, the number,
      motility, viability (eosin-nigrosin staining), DNA breakage (acridine orange
      staining), nucleus maturity, and sperm morphology (aniline blue staining) were
      analyzed. RESULTS: The average (15.87+/-1.28), motility (35.77+/-2.75), viability
      (40+/-3.03), nucleus maturity (36+/-2.79) and sperm morphology (61.75+/-0.85)
      were decreased significantly in CP group in comparison with control and EP
      groups, whereas EP caused significant increase of these parameters. Also, the
      percentage of DNA damage was increased significantly in CP group (41.75+/-3.75)
      in comparison with control (2+/-0.71) and EP groups (22.5+/-4.13). CONCLUSION:
      The results of this study revealed ameliorating effects of EP on sperm quality of
      CP treated animals.

PMID- 26221129
TI  - Hysterosalpingographic findings in women with genital tuberculosis.
AB  - BACKGROUND: Genital tuberculosis (TB) is an important cause of infertility in the
      developing countries, where hysterosalpingography (HSG) remains an initial
      diagnostic procedure in the evaluation of tubal and peritoneal factors leading to
      infertility. OBJECTIVE: The aim of this study was to determine the HSG findings
      of genital TB in infertile women. MATERIALS AND METHODS: We retrospectively
      reviewed HSG findings in 20 women with genital tuberculosis. HSG was performed in
      these women as part of infertility work up over 5 years. The other diagnostic
      procedures used included endometrial curettage and biopsy, histological
      examination, culture, laparoscopy, hysteroscopy and polymerase chain reaction.
      RESULTS: The mean age of the participants was 30.5+/-8 years. All women had
      clinical history of infertility for at least 4 years. Women presented with pelvic
      abdominal pain (30-35%) and menstrual disturbances (20-25%). Reviewing 20 cases
      of female genital TB were encountered various presentations on HSG. CONCLUSION:
      HSG is an invaluable procedure in suggesting the diagnosis of genital TB in
      patients being investigated for infertility.

PMID- 26221130
TI  - Association of androgen receptor GGN repeat length polymorphism and male
      infertility in Khuzestan, Iran.
AB  - BACKGROUND: Androgens play critical role in secondary sexual and male gonads
      differentiations such as spermatogenesis, via androgen receptor. The human
      androgen receptor (AR) encoding gene contains two regions with three nucleotide
      polymorphic repeats (CAG and GGN) in the first exon. Unlike the CAG repeats, the
      GGN has been less studied because of technical difficulties, so the functional
      role of these polymorphic repeats is still unclear. OBJECTIVE: The goal of this
      study was to investigate any relationship between GGN repeat length in the first
      exon of AR gene and idiopathic male infertility in southwest of Iran. MATERIALS
      AND METHODS: This is the first study on GGN repeat of AR gene in infertile male
      in Khuzestan, Iran. We used polymerase chain reaction (PCR) and polyacrylamide
      gel electrophoresis to categorize GGN repeat lengths in 72 infertile and 72
      fertile men. Afterwards we sequenced the PCR products to determine the exact
      length of GGN repeat in each category. Our samples included 36 azoospermic and 36
      oligozoospermic men as cases and 72 fertile men as control group. RESULTS: We
      found that the numbers of repeats in the cases range from 18 to 25, while in the
      controls this range is from 20 to 28. The results showed a significant relation
      between the length of GGN repeat and fertility (p=0.015). The most frequent
      alleles were alleles with 24 and 25 repeats respectively in case and control
      groups. On the other hand no significant differences were found between Arab and
      non-Arab cases by considering GGN repeat lengths (p=0.234). CONCLUSION: Due to
      our results, there is a significant association between the presence of allele
      with 24 repeats and susceptibility to male infertility. Therefore this
      polymorphism should be considered in future studies to clarify etiology of
      disorders related to androgen receptor activity.

PMID- 26221131
TI  - Clinical application of operative hysteroscopy in treatment of complex
      hydrosalpinx prior to IVF.
AB  - BACKGROUND: In vitro fertilization and embryo transfer (IVF-ET) is the best
      option for patients with hydrosalpinx. However, if hydrosalpinges is not pre
      treated, the therapeutic outcomes of IVF-ET would be compromised. OBJECTIVE: This
      study aims to investigate the safety and effects of operative hysteroscopy in the
      treatment of patients with hydrosalpinx prior to IVF-ET, who were not indicated
      for laparotomy due to extensive pelvic adhesion. MATERIALS AND METHODS: The study
      analyses retrospectively data from 10 women with hydrosalpinx, who were unable to
      undergo laparotomy due to extensive pelvic adhesion and treated by operative
      hysteroscopy prior to IVF-ET, and was assessed the effects and safety of the
      procedure. RESULTS: Postoperative Hystero-salpingography demonstrated complete
      tubal occlusion of the diseased side in all cases. Being applied with IVF-ET for
      fertility after their hysteroscopy operation, 5 out of 10 patients acquired
      clinical pregnancy. CONCLUSION: Hysteroscopic tubal occlusion of the proximal
      part of the hydrosalpinx can effectively prevent the hydrops backflow to
      endometrial cavity and benefit subsequent implantation in the course of assisted
      reproduction without significant complications.

PMID- 26221132
TI  - Designing Artificial Neural Networks Using Particle Swarm Optimization
      Algorithms.
AB  - Artificial Neural Network (ANN) design is a complex task because its performance
      depends on the architecture, the selected transfer function, and the learning
      algorithm used to train the set of synaptic weights. In this paper we present a
      methodology that automatically designs an ANN using particle swarm optimization
      algorithms such as Basic Particle Swarm Optimization (PSO), Second Generation of
      Particle Swarm Optimization (SGPSO), and a New Model of PSO called NMPSO. The aim
      of these algorithms is to evolve, at the same time, the three principal
      components of an ANN: the set of synaptic weights, the connections or
      architecture, and the transfer functions for each neuron. Eight different fitness
      functions were proposed to evaluate the fitness of each solution and find the
      best design. These functions are based on the mean square error (MSE) and the
      classification error (CER) and implement a strategy to avoid overtraining and to
      reduce the number of connections in the ANN. In addition, the ANN designed with
      the proposed methodology is compared with those designed manually using the well
      known Back-Propagation and Levenberg-Marquardt Learning Algorithms. Finally, the
      accuracy of the method is tested with different nonlinear pattern classification
      problems. 

PMID- 26221133
TI  - Localized Ambient Solidity Separation Algorithm Based Computer User Segmentation.
AB  - Most of popular clustering methods typically have some strong assumptions of the
      dataset. For example, the k-means implicitly assumes that all clusters come from
      spherical Gaussian distributions which have different means but the same
      covariance. However, when dealing with datasets that have diverse distribution
      shapes or high dimensionality, these assumptions might not be valid anymore. In
      order to overcome this weakness, we proposed a new clustering algorithm named
      localized ambient solidity separation (LASS) algorithm, using a new isolation
      criterion called centroid distance. Compared with other density based isolation
      criteria, our proposed centroid distance isolation criterion addresses the
      problem caused by high dimensionality and varying density. The experiment on a
      designed two-dimensional benchmark dataset shows that our proposed LASS algorithm
      not only inherits the advantage of the original dissimilarity increments
      clustering method to separate naturally isolated clusters but also can identify
      the clusters which are adjacent, overlapping, and under background noise.
      Finally, we compared our LASS algorithm with the dissimilarity increments
      clustering method on a massive computer user dataset with over two million
      records that contains demographic and behaviors information. The results show
      that LASS algorithm works extremely well on this computer user dataset and can
      gain more knowledge from it. 

PMID- 26221134
TI  - Solving Single Machine Total Weighted Tardiness Problem with Unequal Release Date
      Using Neurohybrid Particle Swarm Optimization Approach.
AB  - A particle swarm optimization algorithm (PSO) has been used to solve the single
      machine total weighted tardiness problem (SMTWT) with unequal release date. To
      find the best solutions three different solution approaches have been used. To
      prepare subhybrid solution system, genetic algorithms (GA) and simulated
      annealing (SA) have been used. In the subhybrid system (GA and SA), GA obtains a
      solution in any stage, that solution is taken by SA and used as an initial
      solution. When SA finds better solution than this solution, it stops working and
      gives this solution to GA again. After GA finishes working the obtained solution
      is given to PSO. PSO searches for better solution than this solution. Later it
      again sends the obtained solution to GA. Three different solution systems worked
      together. Neurohybrid system uses PSO as the main optimizer and SA and GA have
      been used as local search tools. For each stage, local optimizers are used to
      perform exploitation to the best particle. In addition to local search tools,
      neurodominance rule (NDR) has been used to improve performance of last solution
      of hybrid-PSO system. NDR checked sequential jobs according to total weighted
      tardiness factor. All system is named as neurohybrid-PSO solution system. 

PMID- 26221135
TI  - CT Imaging Findings after Stereotactic Radiotherapy for Liver Tumors.
AB  - Purpose. To study radiological response to stereotactic radiotherapy for focal
      liver tumors. Materials and Methods. In this IRB-approved, HIPAA-compliant study
      CTs of 68 consecutive patients who underwent stereotactic radiotherapy for liver
      tumors between 01/2006 and 01/2010 were retrospectively reviewed. Two independent
      reviewers evaluated lesion volume and enhancement pattern of the lesion and of
      juxtaposed liver parenchyma. Results. 36 subjects with hepatocellular carcinoma
      (HCC), 25 with liver metastases, and seven with cholangiocarcinoma (CCC) were
      included in study. Mean follow-up time was 5.6 +/- 7.1 months for HCC, 6.4 +/-
      5.1 months for metastases, and 10.1 +/- 4.8 months for the CCC. Complete response
      was seen in 4/36 (11.1%) HCCs and 1/25 (4%) metastases. Partial response (>30%
      decrease in long diameter) was seen in 25/36 (69%) HCCs, 14/25 (58%) metastases,
      and 7/7 (100%) of CCCs. Partial response followed by local recurrence (>20%
      increase in long diameter from nadir) occurred in 2/36 (6%) HCCs and 4/25 (17%)
      metastases. Liver parenchyma adjacent to the lesion demonstrated a prominent halo
      of delayed enhancement in 27/36 (78%) of HCCs, 19/21 (91%) of metastases, and 7/7
      (100%) of CCCs. Conclusion. Sustainable radiological partial response to
      stereotactic radiotherapy is most frequent outcome seen in liver lesions.
      Prominent halo of delayed enhancement of the adjacent liver is frequent finding. 

PMID- 26221137
TI  - Neutrophil Gelatinase-Associated Lipocalin: A New Marker of Renal Function in C
      Related End Stage Liver Disease.
AB  - Background/Aims. Renal impairment is a common complication of cirrhosis. Serum
      creatinine is less sensitive in these patients. Measurement of the glomerular
      filtration rate (GFR) is the gold standard but time consuming. The aim is to
      validate plasma NGAL (pNGAL) and urinary NGAL (uNGAL) as markers of renal
      function in patients with HCV related cirrhosis. Patient and Methods. One hundred
      HCV related end stage liver cirrhosis patients were randomized into two groups:
      Group I (n = 35), patients with GFR < 60 mL/m measured by isotope scanning of the
      kidney (Renogram), and Group II (n = 65), patients with GFR >= 60 mL/m. The pNGAL
      and uNGAL were measured within 2 days of the Renogram. Results. Both groups were
      matched with age, sex, and Child Pugh score. There was statistically significant
      difference between both groups regarding serum creatinine (1.98 +/- 1.04 versus
      1.38 +/- 0.88 mg/dL; p = 0.003) and pNGAL level (5.79 +/- 2.06 versus 7.25 +/-
      3.30 ng/dL; p = 0.019). Both groups were comparable (p > 0.05) for the uNGAL
      (6.00 +/- 0.78 versus 6.03 +/- 0.96 ng/mL). Unlike uNGAL, the pNGAL positively
      correlated with total GFR by Renogram (r = 0.3; p = 0.001). With a cutoff >=4
      ng/mL, pNGAL had 94.3% sensitivity and 1.5% specificity and PPV = 34, NPV = 33.3,
      LR+ = -175.1, and LR- = -60.6. Conclusion. The pNGAL is a promising marker of the
      renal function in patients with cirrhosis. 

PMID- 26221136
TI  - A New Twist to a Chronic HCV Infection: Occult Hepatitis C.
AB  - Background. The prevalence of occult hepatitis C infection (OCI) in the
      population of HCV-RNA negative but anti-HCV positive individuals is presently
      unknown. OCI may be responsible for clinically overt recurrent disease following
      an apparent sustained viral response (SVR) weeks to years later. Purpose. To
      review the available current literature regarding OCI, prevalence, pathogenic
      mechanisms, clinical characteristics, and future directions. Data Sources.
      Searching MEDLINE, article references, and national and international meeting
      abstracts for the diagnosis of OCI (1990-2014). Data Synthesis. The long-term
      followup of individuals with an OCI suggests that the infection can be transient
      with the loss of detectable HCV-RNA in PPBMCs after 12-18 months or alternatively
      exist intermittently and potentially long term. The ultimate outcome of HCV
      infection is decided by interplay between host immune responses, antiviral
      therapies, and the various well-identified viral evasion mechanisms as well as
      the presence of HCV infection within extrahepatic tissues. Conclusion. The
      currently widely held assumption of a HCV-cure in individuals having had "SVR"
      after 8-12 weeks of a course of DAA therapy as recently defined may not be
      entirely valid. Careful longitudinal followup utilizing highly sensitive assays
      and unique approaches to viral isolation are needed. 

PMID- 26221138
TI  - Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active
      Graves' Orbitopathy.
AB  - Aim. To study the efficacy and safety of subantimicrobial dose (SD)
      doxycycline(50 mg/d) in patients with active and moderate-to-severe Graves'
      orbitopathy (GO). Methods. Thirteen patients with active and moderate-to-severe
      GO received once daily oral doxycycline (50 mg/d) for 12 wk. Treatment response
      at 24 wk was used as the primary outcome, measured by a composite of improvement
      in Clinical Activity Score (CAS), diplopia, motility, soft tissue swelling,
      proptosis, and eyelid aperture. Secondary outcome was the change of quality of
      life score (QoL, including visual functioning subscale and appearance subscale).
      Adverse events were also recorded. Results. Overall improvement was noted in
      eight out of 13 patients (61.5%, 95% CI 31.6%-86.1%). Both CAS and soft tissue
      swelling significantly ameliorated in eight patients at 24 wk. Five patients
      (38.5%) had improvement in ocular motility of >=8 degrees. Eyelid aperture
      (46.2%) also decreased remarkably. For QoL, a significant improvement in
      appearance subscale (P = 0.008) was noted during the study, whereas no difference
      was observed in visual functioning subscale (P = 0.21). Two patients reported
      mild stomachache at 12 wk. Conclusions. SD doxycycline appears to be effective
      and safe for the treatment of active and moderate-to-severe GO. It might serve as
      a new promising therapeutic strategy for GO. This trial is registered with
      NCT01727973. 

PMID- 26221139
TI  - Thyroid Stimulating but Not Blocking Autoantibodies Are Highly Prevalent in
      Severe and Active Thyroid-Associated Orbitopathy: A Prospective Study.
AB  - The clinical utility of the functional TSH receptor autoantibodies was
      prospectively evaluated in patients with thyroid-associated orbitopathy (TAO).
      Ophthalmic, endocrine, and serological investigations were performed in 101
      consecutive patients with severe and active TAO. Serum thyroid stimulating (TSAb)
      and blocking (TBAb) antibody levels were measured with two bioassays using cells
      that express a chimeric TSH receptor and CRE-dependent luciferase. TSAb results
      are expressed as percentage of specimen-to-reference ratio (SRR %). Blocking
      activity is defined as percent inhibition of luciferase expression relative to
      induction with bovine TSH alone. All 101 consecutively followed-up patients with
      severe and active TAO were TBAb negative. In contrast, 91 (90%) were TSAb
      positive of whom 90 had Graves' disease. Serum TSAb levels correlated with the
      diplopia score (P = 0.016), total severity eye score (P = 0.009), proptosis (P =
      0.007), lid aperture (P = 0.003), upper lid retraction (P = 0.006), keratopathy
      (P = 0.04), and thyroid binding inhibiting immunoglobulins (TBII, P < 0.001) and
      negatively with the duration of TAO (P = 0.002). Median serum values of TSAb were
      SRR% 418 (range 28% to 795%). TSAb, not TBAb, are highly prevalent in
      severe/active TAO and serum TSAb levels correlate with clinical disease severity.

PMID- 26221140
TI  - Predictors of the Dose-Effect Relationship regarding Unilateral Inferior Rectus
      Muscle Recession in Patients with Thyroid Eye Disease.
AB  - Purpose. To evaluate whether inferior rectus muscle (IRM) thickness, the degree
      of adipose change in the IRM, smoking status, and the previous history of orbital
      radiotherapy can predict the dose-effect relationship regarding unilateral IRM
      recession in thyroid eye disease (TED). Methods. Twenty-five patients were
      retrospectively reviewed. We calculated the largest IRM cross-sectional area and
      evaluated the degree of adipose change in the IRM using magnetic resonance
      imaging. The degree of adipose change and smoking status were classified using
      grading scales (0-3); previous orbital radiotherapy was graded as 0 when a
      history was not available and 1 when it was available. The correlation between
      the dose-effect relationship and the hypothesized predictive factors was
      evaluated using stepwise multiple regression analysis. Results. The multiple
      regression model, with the exception of the history of the previous orbital
      radiotherapy, estimated a significant dose-effect relationship for the parameters
      evaluated (Y DOSE-EFFECT = 0.013X IRM AREA  - 0.222X ADIPOSE  - 0.102X SMOKING +
      1.694; r = 0.668; adjusted r (2) = 0.367; P = 0.005). Conclusions. The dose
      effect relationship regarding unilateral IRM recession in TED could be predicted
      using IRM thickness, degree of intramuscular adipose change, and smoking status
      but could not be predicted using the previous orbital radiotherapy history. 

PMID- 26221141
TI  - Liver Dysfunction Associated with Intravenous Methylprednisolone Pulse Therapy in
      Patients with Graves' Orbitopathy.
AB  - Intravenous methylprednisolone (IVMP) pulse therapy is the first-line treatment
      for the active phase of moderate to severe Graves' orbitopathy (GO). However,
      acute and severe liver damage has been reported during and after IVMP therapy. In
      this retrospective study, we investigated risk factors for liver dysfunction
      during and after IVMP therapy based on 175 Japanese patients with moderate to
      severe GO and treated at our center between 2003 and 2011. The results showed
      that seven patients developed severe liver dysfunction with elevated serum
      alanine aminotransferase (ALT > 300 U/L). Mild (40-100 U/L) and moderate (100-300
      U/L) increases of ALT occurred in 62 patients (35%) and 10 patients (6%),
      respectively. Liver dysfunction was more frequently observed in males, in
      patients receiving high-dose methylprednisolone, and patients aged over 50 years.
      Preexistent viral hepatitis was significantly associated with liver dysfunction
      (65% in patients positive for hepatitis B core antibody and patients positive for
      hepatitis C virus antibodies). Our study confirmed the association of liver
      dysfunction with IVMP during and after treatment. It suggests that, in patients
      with GO, evaluation of preexisting risk factors-including viral hepatitis-and
      careful weekly monitoring of liver function during IVMP therapy and monthly
      thereafter for 12 months are warranted. 

PMID- 26221142
TI  - Results after En Bloc Lateral Wall Decompression Surgery with Orbital Fat
      Resection in 111 Patients with Graves' Orbitopathy.
AB  - Purpose. To evaluate the effect of en bloc lateral wall decompression with
      additional orbital fat resection in terms of exophthalmos reduction and
      complications. Methods. A retrospective, noncomparative case series study from
      1999 to 2011 (chart review) in Graves' orbitopathy (GO) patients. The
      standardized surgical technique involved removal of the lateral orbital wall
      including the orbital rim via a lid crease approach combined with additional
      orbital fat resection. Exophthalmos, diplopia, retrobulbar pressure sensation,
      and complications were analyzed pre- and postoperatively. Results. A total of 111
      patients (164 orbits) with follow-up >3 months were analysed. Mean exophthalmos
      reduction was 3.05mm and preoperative orbital pressure sensation resolved or
      improved in all patients. Visual acuity improved significantly in patients
      undergoing surgery for rehabilitative or vision threatening purposes.
      Preoperative diplopia improved in 10 patients (9.0%) but worsened in 5 patients
      (4.5%), necessitating surgical correction in 3 patients. There were no
      significant complications; however, one patient had slight hollowing of the
      temporalis muscle around the scar that did not necessitate revision, and another
      patient with a circumscribed retraction of the scar itself underwent surgical
      correction. Conclusions. The study confirms the efficiency of en bloc lateral
      wall decompression in GO in a large series of patients, highlighting the low risk
      of disturbance of binocular functions and of cosmetic blemish in the temporal
      midface region. 

PMID- 26221143
TI  - Obstructive Jaundice as Initial Presentation of Multiple Myeloma: Case
      Presentation and Literature Review.
AB  - Multiple myeloma is a malignant plasma-cell disorder that primarily involves the
      bone marrow, but extramedullary involvement is becoming increasingly common
      (Blade et al., 2012) both at initial presentation and follow-up. Most common
      initial presentations for multiple myeloma include generalized fatigue, renal
      insufficiency, bone pain, and recurrent bacterial infections. We present a case
      of a healthy 55-year-old man that presented to the emergency department with a
      three-week history of anorexia and jaundice without any past medical history.
      Patient's initial labs were significant for hyperbilirubinemia and elevated liver
      function enzymes (AST, ALT, ALP, and GGT). Additional laboratory workup was
      significant for mild hypercalcemia and increased protein gap. MRI and ERCP
      suggested primary sclerosing cholangitis but were not diagnostic. Liver biopsy
      illustrated plasma-cell infiltration and bone marrow biopsy diagnosed multiple
      myeloma with extramedullary disease. Patient was started on dexamethasone,
      bortezomib, and cyclophosphamide, but, despite this aggressive regimen, the
      patient continued to decline. We take this opportunity to present this atypical
      presentation of a common hematological malignancy and review the associated
      literature. 

PMID- 26221144
TI  - Angiogenic Potential of Human Neonatal Foreskin Stromal Cells in the Chick Embryo
      Chorioallantoic Membrane Model.
AB  - Several studies have demonstrated the multipotentiality of human neonatal
      foreskin stromal cells (hNSSCs) as being able to differentiate into adipocytes
      and osteoblasts and potentially other cell types. Recently, we demonstrated that
      hNSSCs play a role during in vitro angiogenesis and appear to possess a capacity
      to differentiate into endothelial-like cells; however, their angiogenic potential
      within an ex vivo environment remains unclear. Current study shows hNSSCs to
      display significant migration potential in the undifferentiated state and high
      responsiveness in the in vitro wound healing scratch assay. When hNSSCs were
      seeded onto the top of the CAM, human von Willebrand factor (hVWF), CD31, smooth
      muscle actin (SMA), and factor XIIIa positive cells were observed in the chick
      endothelium. CAMs transplanted with endothelial-differentiated hNSSCs displayed a
      higher number of blood vessels containing hNSSCs compared to CAMs transplanted
      with undifferentiated hNSSCs. Interestingly, undifferentiated hNSSCs showed a
      propensity to differentiate towards ectoderm with indication of epidermal
      formation with cells positive for CD1a, CK5/6, CK19, FXIIIa, and S-100 cells,
      which warrant further investigation. Our findings imply a potential angiogenic
      role for hNSSCs ex vivo in the differentiated and undifferentiated state, with
      potential contribution to blood vessel formation and potential application in
      tissue regeneration and vascularization. 

PMID- 26221145
TI  - Differential Reponses of Hematopoietic Stem and Progenitor Cells to mTOR
      Inhibition.
AB  - Abnormal activation of the mammalian target of rapamycin (mTOR) signaling pathway
      has been observed in a variety of human cancers. Therefore, targeting of the mTOR
      pathway is an attractive strategy for cancer treatment and several mTOR
      inhibitors, including AZD8055 (AZD), a novel dual mTORC1/2 inhibitor, are
      currently in clinical trials. Although bone marrow (BM) suppression is one of the
      primary side effects of anticancer drugs, it is not known if pharmacological
      inhibition of dual mTORC1/2 affects BM hematopoietic stem and progenitor cells
      (HSPCs) function and plasticity. Here we report that dual inhibition of mTORC1/2
      by AZD or its analogue (KU-63794) depletes mouse BM Lin(-)Sca-1(+)c-Kit(+) cells
      in cultures via the induction of apoptotic cell death. Subsequent colony-forming
      unit (CFU) assays revealed that inhibition of mTORC1/2 suppresses the clonogenic
      function of hematopoietic progenitor cells (HPCs) in a dose-dependent manner.
      Surprisingly, we found that dual inhibition of mTORC1/2 markedly inhibits the
      growth of day-14 cobblestone area-forming cells (CAFCs) but enhances the
      generation of day-35 CAFCs. Given the fact that day-14 and day-35 CAFCs are
      functional surrogates of HPCs and hematopoietic stem cells (HSCs), respectively,
      these results suggest that dual inhibition of mTORC1/2 may have distinct effects
      on HPCs versus HSCs. 

PMID- 26221146
TI  - Efficacy of Low-Dose Ciclesonide and Fluticasone Propionate for Mild to Moderate
      Persistent Asthma.
AB  - BACKGROUND: The aim of this study was to compare the efficacy of ciclesonide (80
      mg/day) and fluticasone propionate (200 mg/day) for mild to moderate persistent
      asthma. MATERIALS AND METHODS: Female and male patients older than 12 years with
      a history of persistent bronchial asthma for at least 6 months were enrolled.
      Patients were eligible to enter into a 2-week run-in period before randomization
      (baseline) if they had received inhaled corticosteroids (fluticasone propionate
      250 MUg/day or equivalent) at a constant dose during the last 4 weeks before the
      run-in period. In order to enter into the double blind 18-week treatment period,
      patients had to have a forced expiratory volume in 1s (FEV1) of 61-90% of
      predicted and a decrease in FEV1 throughout the run-in period of more than 10%.
      Patients (n =230) were assigned to ciclesonide 80 mg once daily or fluticasone
      propionate 100 mg twice daily group. The primary outcome variable was change in
      FEV1 compared to its baseline value. Secondary outcome variables were asthma
      specific quality of life and asthma control. RESULTS: Both drugs significantly
      increased FEV1 and other lung function parameters compared to baseline (P<
      0.0001, both groups, all variables). Progress in the percentage of days with no
      asthma symptoms and no use of rescue medication and asthma-specific quality of
      life were similar in the two treatment groups. CONCLUSION: Ciclesonide at a dose
      of 80 MUg once daily can provide efficient maintenance therapy for mild to
      moderate persistent asthma.

PMID- 26221147
TI  - Telomere Shortening in Blood Leukocytes of Patients with Chronic Obstructive
      Pulmonary Disease.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is characterized by
      airflow limitation that is not completely reversible by administration of inhaled
      bronchodilators. Many studies propose that telomere length shortening might have
      occurred in COPD patients. We aimed to determine the telomere length in COPD
      patients and compare the results of non-smoking and smoking control subjects.
      MATERIALS AND METHODS: In our case-control study, 84 clinically stable COPD
      patients were recruited on admission to Masih Daneshvari Hospital. Eighty-five
      healthy controls were also selected including 45 non-smokers and 40 smokers
      admitted for diseases other than COPD. Spirometry was done for all subjects.
      Telomere length was measured by quantitative real time PCR as described by
      Cawthon. The telomere repeat copy number (T) to single-gene copy number (S) ratio
      was calculated using the comparative Ct method. RESULTS: The mean +/-SD of age
      was 64.33+/-10.04 years in patients and 65.06 +/-10.02 years in controls
      (P=0.693). The mean +/-SD of FEV1 was 1.62+/-0.75 L in patients, 2.84+/-0.54 L in
      smoker controls and 2.83+/-0.56 L in non-smoker controls; significant differences
      were detected in this regard between cases and controls (P<0.001). T/S ratio was
      significantly lower in COPD patients (0.61+/-0.08) than in the control subjects
      (0.69+/-0.09) (P<0.001). However, telomere length was shorter in the patients
      than in controls in each age group (P<0.001). Additionally, there were no
      statistically significant differences in telomere length between the smoker and
      non-smoker control subjects. Regarding the correlation between BMI and telomere
      length, there were no significant differences among the patients and control
      groups. CONCLUSION: In conclusion, we found that telomere length in COPD patients
      was shorter than that in smoker and non-smoker controls, irrespective of age,
      sex, spirometric variables, BMI and history of cigarette smoking.

PMID- 26221148
TI  - Adherence to Venous Thromboprophylaxis Guidelines for Medical and Surgical
      Inpatients of Teaching Hospitals, Shiraz-Iran.
AB  - BACKGROUND: Venous thromboembolism (VTE) exerts a considerable burden on the
      health care systems. Although many practice guidelines have been developed
      regarding prophylaxis and treatment of venous thromboembolism, there is a large
      gap between the recommendations and the medical practice in health care centers.
      In this study, we tried to assess adherence of the medical team to guidelines for
      venous thromboprophylaxis in medical and surgical wards of teaching hospitals
      affiliated to Shiraz University of Medical Sciences. MATERIALS AND METHODS: In
      this cross-sectional descriptive study, a total number of 500 patients were
      recruited among hospitalized patients in neurosurgery, orthopedics, general
      surgery, internal medicine, and obstetrics & gynecology departments and surgical
      and medical intensive care units. Afterwards, adherence to thromboprophylaxis
      guidelines was assessed by comparing the medical records of patients with proper
      indications extracted from the American College of Chest Physicians Guidelines
      for VTE prophylaxis (ACCP, 9(th) edition). In other words, for each patient a
      comparison between proper indications of receiving thromboprophylaxis and the
      regimen used in practice was made. RESULTS: Out of 472 patients assessed with
      respect to the appropriateness of the administered prophylaxis, 212 (45.1%) had
      received proper type of thromboprophylaxis with regard to ACCP guidelines.
      Orthopedic surgical wards showed the highest rate of appropriateness while
      neurosurgical wards showed the lowest rate of adherence (76% vs. 1.8%). The
      overall rate of inappropriateness was 54.9% (260 patients). Inappropriateness was
      divided into 3 categories: 1) patients had absolute indications to receive
      thromboprophylaxis but were not provided with any type of prophylaxis in practice
      (171 patients, 36.2% of total), 2) in presence of absolute indications, incorrect
      type of prophylaxis was administered (52 patients, 11% of total), 3) in absence
      of indications for thromboprophylaxis, patients received some forms of
      prophylaxis (35 patients, 7.4% of total). CONCLUSION: The findings of the present
      study showed that prophylaxis are not properly utilized and physicians' practices
      vary considerably among different specialties.

PMID- 26221149
TI  - Estimated Prevalence of Venous Thromboembolism in Iran: Prophylaxis Still an
      Unmet Challenge.
AB  - BACKGROUND: Inappropriate thromboprophylaxis is a serious problem in Iran. Venous
      thromboembolism (VTE) is one of the most important causes of morbidity in
      patients in surgical and obstetrics departments and intensive care units (ICUs).
      It is a leading preventable cause of mortality among in-patients. This study was
      designed to determine the prevalence of VTE and its epidemiology in an Iranian
      population for the first time. MATERIALS AND METHODS: There is no national
      registry system for keeping VTE records in Iran. To statistically calculate the
      annual prevalence of VTE, we used the prevalence of VTE in presence of each VTE
      predisposing condition and the annual prevalence of each VTE predisposing
      condition in Iran. RESULTS: The average annual number of total adult patients
      with predisposing conditions of deep vein thrombosis (DVT) in Iran was 5,288,272
      people. The mean annual prevalence of DVT in Iran was between 686,928 and
      2,089,738 cases. The mean annual prevalence rate of DVT among the hospitalized
      Iranian adult patients with the risk of DVT was approximately between 129.90 and
      395.16 cases per 1000 patients. CONCLUSION: The mean annual prevalence of DVT
      among the hospitalized Iranian adult patients not receiving prophylaxis is high.
      We also found that appropriate prophylaxis was provided for less than half the
      patients in need.

PMID- 26221150
TI  - Association of High Sensitive CRP Level and COPD Assessment Test Scores with
      Clinically Important Predictive Outcomes in Stable COPD Patients.
AB  - BACKGROUND: High sensitive CRP (hs-CRP) is used as a marker of systemic
      inflammation in chronic obstructive pulmonary disease (COPD). However, we
      hypothesize that the raised hs-CRP is not closely related to the multiple
      consequences of COPD. This study was undertaken to investigate the association of
      COPD assessment test (CAT) score with SpO2, FEV1, body mass index (BMI),
      obstruction, dyspnea and exercise capacity (BODE) index and COPD exacerbation
      rate and compare it with the association to serum hs-CRP level. MATERIALS AND
      METHODS: Sixty patients with stable COPD referred to the pulmonology clinic of
      Ardabil Imam Khomeini Hospital were included in this study. SpO2, 6-minute walk
      distance (6MWD), body mass index, BODE index, and pulmonary function test as well
      as exacerbation rate were determined in COPD patients. Then, the CAT
      questionnaire was completed by patients. Serum level of hs-CRP was measured in
      all patients and 15 controls. We statistically compared the relationships and
      correlations among the variables. RESULTS: Hs-CRP level was significantly raised
      in patients (P=0.005). In these patients, the correlation of hs-CRP level with
      BODE index was significant (P=0.008). However, the correlation of hs-CRP with
      SpO2 and FEV1 was not significant (P=0.47 and P=0.17, respectively). Also, the
      correlation of CAT score with SpO2, FEV1, BODE index, and exacerbation rate in
      the previous year was significant (P<0.001, P<0.001, P<0.001 and P=0.017,
      respectively). CONCLUSION: SpO2, FEV1, BODE index and exacerbation rate are more
      correlated with CAT scores than with the serum level of hs-CRP in stable COPD
      patients. The findings of this study should be considered in management of stable
      COPD patients.

PMID- 26221151
TI  - Efficacy of the New Perilaryngeal Airway (CobraPLATM) Versus the Laryngeal Mask
      Airway (LMATM) to Improve Oropharyngeal Leak Pressure in Obese and Overweight
      Patients.
AB  - BACKGROUND: This study aimed to evaluate the applicability of Cobra perilaryngeal
      airway (Cobra PLATM) for obese patients under general anesthesia and also to
      compare the results with those of classic laryngeal mask airway (LMATM).
      MATERIALS AND METHODS: Seventy-three overweight and obese patients were included
      in this study. The patients were randomly assigned to LMATM or Cobra PLATM
      groups. Time required for intubation, successful intubation attempt, airway
      sealing pressure and incidence of complications including blood staining, sore
      throat and dysphagia were assessed and noted. RESULTS: Thirty-six and 37 patients
      were randomly allocated to LMATM and Cobra PLATM groups, respectively. Most
      patients were males and had Mallampati Class II airway in both groups. The first
      attempt and overall insertion success for Cobra PLATM was significantly higher
      compared to LMA (P<0.05). Airway insertion was more successful (P = 0.027; 94%
      vs. 77%) with Cobra PLATM. Insertion times were similar with Cobra PLATM and
      LMATM (Cobra PLATM, 29.94+/-16.35s; LMATM, 27.00+/-7.88s). The oropharyngeal leak
      pressure in the Cobra PLATM group (24.80+/-0.90 H2O) was significantly higher
      than that in LMATM group (19+/-1 H2O, p<0.001). Sore throat was more frequent in
      the LMATM group although it did not reach statistical significance (Fisher's
      exact test, P = 0.33). Blood staining on airway tube was seen in both groups with
      a higher incidence in the Cobra PLATM group (Fisher's Exact test, P = 0.02).
      Incidence of dysphagia was not different between the two groups. CONCLUSION:
      CobraPLATM was found to be safe with low complications. It provided better airway
      sealing with high rate of the first insertion success for use in obese and
      overweight patients. This study recommends the use of CobraPLATM as a rescue
      device in emergency situations for obese and overweight patients.

PMID- 26221152
TI  - Acute Kidney Injury in ICU Patients Following Non-Cardiac Surgery at Masih
      Daneshvari Hospital: Joint Modeling Application.
AB  - BACKGROUND: Admission to the intensive care unit (ICU) is often complicated by
      early acute kidney injury (AKI). AKI is associated with high rates of mortality
      and morbidity. Risk factors and incidence of AKI have been notably high following
      non-cardiac surgery in the past decade. The aim of this study was to determine
      the hazard rate of AKI, the effect of risk factors of AKI and also to assess the
      changes in urine output (UO) as a predictor of AKI using joint modeling in
      patients undergoing non-cardiac surgery. MATERIALS AND METHODS: In this
      retrospective cohort study, 400 non-cardiac-operated patients admitted during 3
      years to the ICU of Masih Daneshvari Hospital were selected according to the
      consecutive sample selection method. Random mixed effect model and survival model
      were used to assess UO changes and the effect of UO and other risk factors on the
      hazard rate of AKI using joint analysis. RESULTS: AKI occurred in 8.8% of the
      Iranian non-cardiac-operated patients. Survival model showed that the risk of AKI
      in lower diastolic blood pressure (DBP), higher Acute Physiology and Chronic
      Health Evaluation II score (APACHE II score), emergency surgery, longer
      hospitalization and male patients was higher (P=0.001). Using joint modeling, an
      association was found between the risk of AKI and UO (-0.19, P=0.002).
      CONCLUSION: Several predictors were found to be associated with AKI in the
      Iranian patients after non-cardiac surgery. A relationship between longitudinal
      and survival responses was found in this study and joint modeling caused
      considerable improvement in estimations compared to separate longitudinal and
      survival models.

PMID- 26221153
TI  - Association of Sick Building Syndrome with Indoor Air Parameters.
AB  - BACKGROUND: Energy crisis in 1973 led to smaller residential and office buildings
      with lower air changes. This resulted in development of Sick Building Syndrome
      (SBS). The objective of this study was to assess the association of SBS with
      individual factors and indoor air pollutants among employees in two office
      buildings of Petroleum Industry Health Organization in Tehran city. MATERIALS AND
      METHODS: The association between personal and environmental factors and SBS
      symptoms was examined by a reliable and valid combined questionnaire.
      Environmental parameters were measured using calibrated instruments. RESULTS: The
      results suggested that SBS symptoms were more common in women than men. Malaise
      and headache were the most common symptoms in women and men. Throat dryness,
      cough, sputum, and wheezing were less prevalent among employees in both offices.
      Light-intensity was significantly associated with some symptoms such as skin
      dryness (P = 0.049), eye pain (P = 0.026), and malaise (P = 0.043). There were no
      significant differences in prevalence of SBS symptoms between female workers of
      the two offices (P>0.05). CONCLUSION: The main causes of SBS among the employees
      were recycling of air in rooms using fan coils, traffic noise, poor lighting, and
      buildings located in a polluted metropolitan area.

PMID- 26221154
TI  - Bilateral Lymphoblastic Lymphoma of Breast Mimicking Inflammatory Breast Cancer:
      A Case Report and Review of Literature.
AB  - We report a 45 year-old woman who had bilateral breast masses with extradural
      involvement. Pathologic report revealed malignant high-grade lymphoblastic
      lymphoma. Systemic chemotherapy was performed but 3 months later, lesions
      indicating relapse in bone and breast re-appeared. She received salvage
      chemotherapy, but 4 months after that she was expired. 

PMID- 26221155
TI  - Yellow Nail Syndrome: Report of a Case Successfully Treated with Octreotide.
AB  - Yellow nail syndrome (YNS) is an uncommon condition characterized by a triad of
      yellow nail coloration, lymphedema and respiratory tract involvement. This
      syndrome typically affects middle-aged persons. Although several etiologies have
      been described, to date; the exact etiology remains unclear. Different treatment
      plans have been suggested, but all data available emphasize the fact that
      treatment is mainly symptomatic and the underlying disease is not targeted. The
      most reported treatment protocol is chemical pleurodesis combined with alpha
      tocopherol (vitamin E). Hereby, we describe a case of YNS in a 34 year-old woman
      with the onset of symptoms in childhood. The symptoms improved dramatically after
      treatment with octreotide. 

PMID- 26221156
TI  - Seizure-Control Effect of Levatiracetam on Juvenile Myoclonic Epilepsy and Other
      Epileptic Syndromes: Literature Review of Recent Studies.

PMID- 26221157
TI  - Animal Models of Cerebral Palsy: Hypoxic Brain Injury in the Newborn.
AB  - OBJECTIVE: Hypoxic insults are implicated in the spectrum of fetal disorders,
      including cerebral palsy (CP). In view of the major contribution of intrapartum
      risk factors and prematurity to subsequent neurological morbidity and mortality
      in humans, this study aimed to clarify the pathophysiology of brain injury,
      especially periventricular white matter damage (WMD), that occur in utero to the
      immature and near-term fetal CNS. MATERIALS & METHODS: An evaluation of the
      resulting neurological and behavioural phenotype in the newborn was performed by
      utilising a battery of neurobehavioural tests, including the Morris water-maze
      and the open-field test, followed by cerebral MRI and histopathology. RESULTS:
      This study used a murine model to examine the deleterious effects of WMD brought
      about by cerebral hypoxia-ischemia (HI) and the characteristic features of CP in
      mice. Murine models have proven themselves valuable in the area of experimental
      neuroscience. CONCLUSION: Hypoxia-treated mice were observed to demonstrate a
      significant neurofunctional deficit compared with sham mice on two behavioral
      measures. Indeed, different brain regions, including the sensorimotor cortex, the
      striatum, and the hippocampus were noticeably damaged after HI insult, as
      determined by both MRI and histopathology. These results, albeit qualitative in
      nature, appear to support the pre-existing finding that the long-term
      neurofunctional outcome in animal subjects with CP is strongly associated with
      the anatomical extent and pattern of cerebral damage as determined by both
      delayed neuroimaging and histopathology.

PMID- 26221158
TI  - Comparison of the Efficacy of Combination Therapy of Prednisolone - Acyclovir
      with Prednisolone Alone in Bell's Palsy.
AB  - OBJECTIVE: Bell's palsy is a rapid onset, usually, unilateral paralysis of the
      facial nerve that causes significant changes in an individual's life such as a
      decline in personal, social, and educational performance. This study compared
      efficacy of combined prednisolone and acyclovir therapy with prednisolone alone.
      MATERIALS & METHODS: This study is a randomized controlled trial conducted on 43
      Children (2-18 years old) with Bell's palsy. The first group of 23 patients was
      treated with prednisolone and the remaining patients were treated with a
      combination of prednisolone and acyclovir. The required data were extracted,
      using an informational form based on the House-Brackmann Scale, which grades
      facial nerve paralysis. The data were analyzed with Mann-Whitney test using SPSS
      version 16. RESULTS: The mean age of the first and second group were 8.65 +/-
      5.07 and 8.35 +/- 4.92 years, respectively, (p=0.84). Sixty one percent and 39%
      of patients in the first group, and 45% and 55% of patients in the second group
      were male and female, respectively. No significant differences exist between the
      groups in terms of age and gender. The rate of complete recovery was 65.2% in
      group I and 90% in the group II (p=0.04). CONCLUSION: The results of this study
      showed that the combined prednisolone and acyclovir therapy of patients with
      Bell's palsy is far more effective than treatment with prednisolone alone.
      Actually, age and gender had no impact on the rate of recovery.

PMID- 26221159
TI  - Brainstem Auditory Evoked Potentials in Boys with Autism: Still Searching for the
      Hidden Truth.
AB  - OBJECTIVE: Brainstem auditory evoked potentials (BAEPs) have long been utilized
      in the investigation of auditory modulation and, more specifically, auditory
      brainstem functions in individuals with autism. Although most investigators have
      reported significant abnormalities, no single BAEPs pattern has yet been
      identified. The present study further delineates the BAEPs deficits among
      subjects with autism. MATERIALS & METHODS: BAEPs were recorded in 43 male
      patients, aged 35-104 months, who underwent standard evaluations after receiving
      a diagnosis of autism. The control group consisted of 43 age-matched typically
      developing boys. The study took place in a tertiary neurodevelopmental center
      over a period of two years. RESULTS: The mean values of all absolute and/or
      interpeak latencies were longer in patients when compared to controls, albeit the
      differences were not significant for any of the parameters. Prolonged or
      shortened absolute/interpeak latencies (control group mean +/- 2.5SD) were
      unilaterally or bilaterally identified in 33% of patients, compared to 9% of
      controls. The most frequent findings included prolongation of absolute latencies
      I, V and III, followed by shortening of interpeak latency I-V. In addition,
      abnormalities (either shortening or prolongation) of absolute latencies I and V,
      as well as interpeak latency I-V, were significantly more common among patients.
      Taken together, BAEPs in 23% of patients were indicative of a clinically abnormal
      response in 32% of patients. CONCLUSION: As can be easily concluded, BAEPs
      abnormalities characterize only a subset of subjects with autism, who may be
      important to identify clinically. The latter individuals may benefit from
      targeted intervention to utilize brainstem plasticity.

PMID- 26221160
TI  - The Etiology and Clinical Evaluations of Neonatal Seizures in Kashan, IRAN.
AB  - OBJECTIVE: Detection of seizure, its etiology, and clinical types is important
      for guiding therapy. This study was designed to evaluate the etiology and
      clinical evaluations of neonatal seizures in Kashan, Iran. MATERIALS AND METHODS:
      The data of 100 hospitalized neonates with a complaint of seizures in Kashan
      City, from January 2006 to January 2011 were evaluated. The pediatric neurologist
      made the final diagnosis. The gestational age, neonate admission age, type of
      delivery, and laboratory and radiological investigations were reviewed from the
      medical records. The relation of seizure etiology and other variables were
      compared using the Chi-square test. All the statistical analyses were performed
      using SPSS (ver 11.5). RESULTS: A total of 100 neonates were hospitalized with a
      diagnosis of seizures. The overall incidence rate of seizures was 2.6 per 1,000
      live births. A total of 59% of seizures happened in the first three days of life.
      The etiologies of seizures were hypoxicischemic encephalopathy (HIE) (36%),
      hyponatremia (12%), hypoglycemia (11%), intracranial hemorrhage (11%), infections
      (10%), hypocalcemia (8%), metabolic disorders (7%), the structural anomalies
      (5%), and hypomagnesaemia (4%). In 23% of neonates, no specific etiology was
      found and 23% had multiple etiologies. In 45% of neonates, the EEG was not
      recorded. The type of the seizures were focal-clonic (26%), tonic (25%),
      multifocal clonic (34%), subtle (11%), and myoclonic (4%). The types of the
      seizure were unrelated to the paraclinical findings. CONCLUSION: Neonatal
      seizures are common and HIE was the main cause of seizures in this study. The
      clinical evaluation of neonatal seizures needs improvement.

PMID- 26221161
TI  - Effects of Neurodevelopmental Therapy on Gross Motor Function in Children with
      Cerebral Palsy.
AB  - OBJECTIVE: Neurodevelopmental treatments are an advanced therapeutic approach
      practiced by experienced occupational therapists for the rehabilitation of
      children with cerebral palsy. The primary challenge in children with cerebral
      palsy is gross motor dysfunction. We studied the effects of neurodevelopmental
      therapy on gross motor function in children with cerebral palsy. MATERIALS &
      METHODS: In a quasi-experimental design, 28 children with cerebral palsy were
      randomly divided into two groups. Neurodevelopmental therapy was given to a first
      group (n=15) with a mean age of 4.9 years; and a second group with a mean age 4.4
      years (n=13) who were the control group. All children were evaluated with the
      Gross Motor Function Measure. Treatments were scheduled for three - one-hour
      sessions per week for 3 months. RESULTS: We obtained statistically significant
      differences in the values between the baseline and post treatment in two groups.
      The groups were significantly different in laying and rolling (P=0.000), sitting
      (0.002), crawling and kneeling (0.004), and standing abilities (P=0.005).
      However, there were no significant differences in walking, running, and jumping
      abilities between the two groups (0.090). CONCLUSION: We concluded that the
      neurodevelopmental treatment improved gross motor function in children with
      cerebral palsy in four dimensions (laying and rolling, sitting, crawling and
      kneeling, and standing). However, walking, running, and jumping did not improve
      significantly.

PMID- 26221162
TI  - Comparison of CPAP with Humidifier, Blender, and T-piece on the Outcome of
      Weaning in Patients with Neurological Disorders.
AB  - OBJECTIVE: The procedure for weaning from mechanical ventilation in many patients
      is a difficult and long process and increases the time of mechanical ventilation.
      There are numerous ways to achieve weaning. One common method is the use of CPAP.
      Considering the lower price of a humidifier, blender, and T-piece compared with
      CPAP and in light of the limited number of studies in this field, the current
      study purposed to compare these two procedures. MATERIALS & METHODS: Fifty-one
      patients with neurological disorders who were under mechanical ventilation and
      ready to wean were allocated randomly into two groups: the CPAP group and the
      humidifier, blender, and T-piece group. Duration of hospital and PICU stay,
      number of days under mechanical ventilation, frequency of reintubation, and
      mortality rate among patients were documented. RESULTS: The patients were 33
      males and 18 females (64.7% and 35.3%, respectively) with an average age of 22.5
      +/- 4.5 months. The main indication for intubation was impending respiratory
      failure. Hospital stay was 22+/-15 and 21+/-13 days for the humidifier and CPAP
      groups, respectively. PICU stay was 13+/-11 and 21+/-13 days for the humidifier
      and CPAP groups, respectively. Re-intubation rates were 17.2% and 45.5% for the
      humidifier and CPAP groups, respectively. Mortality rates were 3.4% and 22.5% for
      the humidifier and CPAP groups, respectively. CONCLUSION: Considering no
      statistically significant difference between the two groups, using the
      humidifier, blender, and T-piece is recommended.

PMID- 26221163
TI  - The Role of Antiepileptic Treatment in the Recurrence Rate of Seizures After
      First Attack: A Randomized Clinical Trial.
AB  - OBJECTIVE: Epilepsy is a serious, potentially life-shortening brain disorder that
      occurs in patients of all ages and races. A total of 2-4% of people have
      experienced seizures at least once in their lifetime. Although treatment usually
      begins after a seizure, it is an important question whether the first cases of
      seizure do need to be treated by antiepileptic drugs. In this manner, we compare
      the recurrence rates of epilepsy in first seizure patients treated with sodium
      valproic acid as an antiepileptic drug versus a placebo. MATERIAL & METHODS: In a
      randomized clinical trial study, 101 first seizure patients were randomly divided
      into two groups: one group was treated with antiepileptic drugs (sodium valproate
      200mg, three times a day) and the other group was given a placebo. The recurrence
      rate of seizures was evaluated and compared between the groups after 6 months of
      follow up. RESULTS: Eight recurrence cases were detected. All recurrence cases
      came from the placebo group, with four patients suffering an additional seizure
      after four months and between 4-6 month follow up. A comparison of recurrence
      rate detected a statistically significant difference between the drug group and
      placebo group. CONCLUSION: Our data shows that the recurrences occurred only in
      the placebo group with the difference between the recurrence rates in the placebo
      versus drug-treated was significant. Our results suggest that drug therapy for
      people after their first seizure attack might reduce the probability of seizure
      recurrence.

PMID- 26221164
TI  - Homocystinuria: A Rare Disorder Presenting as Cerebral Sinovenous Thrombosis.
AB  - Objective Homocystinuria is an inborn error of amino acid metabolism caused by
      cystathionine beta-synthase deficiency that affects methionine metabolism. The
      clinical features are heterogeneous ranging from mental retardation, ectopia
      lentis, and osteoporosis to vascular events such as deep vein thrombosis, sagital
      sinus thrombosis, and myocardial infarction. Cerebral sinovenous thrombosis
      (CVST) is an unusual disorder in children and requires prompt and accurate
      management. Some causal factors for the development of CVST differ between
      children and adults. The majority of cases with CSVT are found to have an
      underlying cause for thrombosis like dehydration, infections, prothrombotic and
      hematologic disorders, malignancy and trauma. Although homocystinuria is usually
      associated with ischemic strokes, CVST as initial clinical presentation of
      homocystinuria is rare in children. In this article, we presented a 10-year old
      boy with seizure, hemiparesis, and ataxia due to CSVT caused by homocystinuria. 

PMID- 26221165
TI  - Biotinidase Deficiency in Newborns as Respiratory Distress and Tachypnea: A Case
      Report.
AB  - OBJECTIVE: Biotin is a coenzyme composed of four carboxylases. It presents in
      amino acid catabolism, fatty acid synthesis, and gluconeogenesis. Biotinidase
      recycles the vitamin biotin. A biotinidase deficiency is a neurocutaneous
      disorder with autosomal recessive inheritance. The symptoms can be successfully
      treated or prevented by administering pharmacological doses of biotin. Although,
      according to neonatal prenatal medicine (2011), a biotinidase deficiency does not
      manifest during the neonatal period. In this study, we report on a case of
      biotinidase deficiency in the first week of birth. CASE REPORT: A 3100 g term boy
      was born via cesarean section. After 3 days, he was referred to the 17th
      Shahrivar Hospital with the chief complaint of tachypnea and grunting. Laboratory
      results revealed that liver and renal function tests, serum electrolytes, and
      blood indexes except ammonia were all normal. Within few days after the
      administration of oral biotin, the patient showed dramatic improvement and was
      discharged. However, within 4 months he was admitted two other times with the
      complaints of diarrhea and pneumonia. Unfortunately, he expired after 4 months.
      According to our results, it seems that clinicians should accurately assess
      suspicious patients and even assess infants for biotinidase deficiency.

PMID- 26221166
TI  - Baclofen Induced Encephalopathy in a 6-Year-Old Boy with Advanced Renal Failure.
AB  - Baclofen is a drug for many diseases for all ages, but it is hazardous in
      patients with renal failure. This article talks about a case of baclofen overdose
      in a child with renal failure. A 6-year-old boy admitted to the emergency
      department with a loss of consciousness, hypotonia, and areflexia following
      administration of 20 mg baclofen (1mg/kg/daily) in total dose for his voiding
      dysfunction. His laboratory tests showed advanced renal failure. After
      withholding the medication and supportive therapy, he recovered completely after
      two days. After arousal, he complained of insomnia, strange sensations on the
      skin, intentional tremors, and ataxia. He left the hospital in good condition in
      three days. Renal function control before baclofen administration is mandatory
      especially in high-risk groups. A total dose of 1mg/kg lead to encephalopathy in
      children with advanced renal failure, with subtle persistent complaints persist
      are often overlooked for a while. 

PMID- 26221167
TI  - Double Cortex Syndrome (Subcortical Band Heterotopia): A Case Report.
AB  - Objective Approximately 5-10% of preschool age children are considered
      developmentally disabled. Brain Magnetic Resonance Imaging (MRI) plays a key role
      in the diagnostic evaluation in these children. Many congenital or acquired brain
      anomalies are revealed with MRIs. Although the majority of these abnormalities
      are sporadic but patients with subcortical band heterotopia or double cortex
      syndrome have sex-linked inheritance. We are going to present the first case in
      Iran from Ahvaz city, which was presented with status epilepticus associated with
      developmental delay and finally diagnosed as double cortex syndrome, because band
      heterotopia cases especially for continuous or generalized form is rare. A 4.5
      year-old developmentally delayed girl was admitted for generalized tonic clonic
      seizure attack of 1 hr, upward gaze, locked mouth, and urinary incontinence
      (status epilepticus) in the child neurology ward. She had a history of recurrent
      seizures that started as febrile seizures since she was 12 months of age and had
      frequent admissions for having recurrent seizure attacks. She was the only child
      of consanguineous parents with negative family history of any neurologic
      problems. She was a product of uneventful term pregnancy, vaginal delivery with a
      low Apgar score at birth who was admitted for six days in the neonatal ward for
      hypotonia and cyanosis. At 4.5 years of age, she had HC: 45cm (<3%) Length: 102
      cm (25-75%), and BW: 18kg (75%). She was able to sit, walk with support, speak a
      few words, and communicate with others. A physical exam was unremarkable. Lab
      data including CBC, blood biochemical, and urinalysis results were all within
      normal limits, but the electroencephalography (EEG) revealed generalized poly
      spike-wave discharges. A brain MRI showed corpus callosal dysplasia, generalized
      band heterotopia, and polymicrogyria. She was discharged home with oral valproate
      and regular outpatient follow-ups. In the diagnostic evaluation of
      developmentally delayed and epileptic children, a brain MRI is strongly
      recommended for accurate diagnosis of anomalies such as neuronal migration
      disorders (band heterotopia) and others, because appropriate therapeutic
      management, prognosis, prevention, and genetic counseling for prenatal diagnosis
      are dependent on definite diagnosis of the proband case. 

PMID- 26221168
TI  - Curative Effects of Fuzheng Huayu on Liver Fibrosis and Cirrhosis: A Meta
      Analysis.
AB  - The Fuzheng Huayu (FZHY) formula is being used in antiliver fibrosis treatment in
      China. For systemic evaluation of the curative effects of FZHY on liver fibrosis
      and cirrhosis progress, a total of 1392 subjects (714 cases and 678 controls)
      were found to be eligible for meta-analysis in this study. Standard mean
      differences (SMDs) with 95% confidence interval (CI) were calculated for changes
      between FZHY groups and controls by employing fixed effects or random effects
      model. In the overall analysis, alanine transaminase (ALT) (P = 0.003, SMD = 
      0.87, 95% CI: -1.46 to -0.29), total bilirubin (TBil) (P = 0.001, SMD = -1.30,
      95% CI: -2.10 to -0.50), hyaluronic acid (HA) (P = 0.000, SMD = -0.94, 95% CI: 
      1.30 to -0.58), laminin (LN) (P = 0.000, SMD = -0.80, 95% CI: -1.20 to -0.41),
      type III procollagen (PC-III) (P = 0.000, SMD = -1.27, 95% CI: -1.93 to -0.60),
      and type IV procollagen (IV-C) (P = 0.000, SMD = -0.78, 95% CI: -1.05 to -0.51)
      were decreased after FZHY treatment; however, albumin (ALB) was increased (P =
      0.037, SMD = 1.10, 95% CI: 0.07 to 2.12) significantly. Furthermore, the Child
      Pugh score was reduced significantly and the life quality was improved after FZHY
      treatment in cirrhosis patients. The results of this meta-analysis indicated that
      FZHY effectively improves the liver function, alleviates hepatic fibrosis,
      decreases Child-Pugh score, and relieves TCM symptoms caused by liver
      dysfunction, indicating that FZHY may contribute to the alleviation of liver
      fibrosis and cirrhosis. 

PMID- 26221170
TI  - Randomized Clinical Trial of the Innovative Bilayered Wound Dressing Made of Silk
      and Gelatin: Safety and Efficacy Tests Using a Split-Thickness Skin Graft Model.
AB  - We developed the novel silk fibroin-based bilayered wound dressing for the
      treatment of partial thickness wounds. And it showed relevant characteristics and
      accelerated the healing of full-thickness wounds in a rat model. This study is
      the clinical evaluation of the bilayered wound dressing to confirm its safety and
      efficacy for the treatment of split-thickness skin donor sites. The safety test
      was performed using a patch model and no evidence of marked and severe cutaneous
      reactions was found. The efficacy test of the bilayered wound dressing was
      conducted on 23 patients with 30 split-thickness skin graft donor sites to
      evaluate healing time, pain score, skin barrier function, and systemic reaction
      in comparison to Bactigras. We found that the healing time of donor site wounds
      treated with the bilayered wound dressing (11 +/- 6 days) was significantly
      faster than those treated with Bactigras (14 +/- 6 days) (p = 10(-6)). The wound
      sites treated with the bilayered wound dressing showed significantly less pain
      and more rapid skin functional barrier recovery than those treated with Bactigras
      (p = 10(-5)). Therefore, these results confirmed the clinical safety and efficacy
      of the bilayered wound dressing for the treatment of split-thickness skin graft
      donor sites. 

PMID- 26221169
TI  - Bathing Effects of Various Seawaters on Allergic (Atopic) Dermatitis-Like Skin
      Lesions Induced by 2,4-Dinitrochlorobenzene in Hairless Mice.
AB  - We evaluated the preventive effects of four types of seawater collected in
      Republic of Korea on hairless mice with 2,4-dinitrochlorobenzene- (DNCB-) induced
      allergic/atopic dermatitis (AD). The anti-inflammatory effects were evaluated by
      measuring tumor necrosis factor- (TNF-) alpha and interleukins (ILs). Glutathione
      (GSH), malondialdehyde (MDA), superoxide anion, and inducible nitric oxide
      synthase (iNOS) were measured to evaluate the antioxidant effects. Caspase-3 and
      poly (ADP-ribose) polymerase (PARP) were observed to measure the antiapoptotic
      effects; matrix metalloproteinase- (MMP-) 9 levels were also evaluated. Mice with
      AD had markedly higher clinical skin severity scores and scratching behaviors;
      higher TNF-alpha and ILs (1beta, 10, 4, 5, and 13) levels; higher MDA, superoxide
      anion, caspase-3, PARP, and MMP-9 levels; and greater iNOS activity. However, the
      severity of AD was significantly decreased by bathing in seawaters, but it did
      not influence the dermal collagen depositions and skin tissue antioxidant defense
      systems. These results suggest that bathing in all four seawaters has protective
      effects against DNCB-induced AD through their favorable systemic and local
      immunomodulatory effects, active cytoprotective antiapoptotic effects, inhibitory
      effects of MMP activity and anti-inflammatory and antioxidative effects. 

PMID- 26221171
TI  - Dynamical Regulation Analysis Identifies Molecular Mechanisms of Fuzheng-Huayu
      Formula against Hepatitis B-Caused Liver Cirrhosis.
AB  - Fuzheng-Huayu (FZHY) tablet was formulated based on Chinese medicine theory in
      treating liver fibrosis. A clinical trial has indicated that FZHY can against
      hepatitis B-caused liver cirrhosis (HBC), but the underlying mechanism of FZHY
      efficacy is unclear. Here, we report that miRNA expression levels are remarkably
      changed when FZHY formula was used in HBC patient's treatment as a paradigm of
      trials. Then, we functionally characterize the significant impact of potential
      kernel miRNAs by miRNA-target network analysis. Enrichment analysis show that the
      FZHY formula dramatically effecting the molecular regulated module in HBC. Thus,
      we infer that FZHY plays a critical function in HBC treatment process and
      directly regulated many important pathways, including but not limited to cell
      cycle, p53 signaling pathway, and TGF-beta signaling pathway, suggesting a new
      strategy for investigating the molecular mechanism of FZHY treatment. 

PMID- 26221173
TI  - Autophagic Cell Death by Poncirus trifoliata Rafin., a Traditional Oriental
      Medicine, in Human Oral Cancer HSC-4 Cells.
AB  - Poncirus trifoliata Rafin. has long been used as anti-inflammatory and
      antiallergic agent to treat gastrointestinal disorders and pulmonary diseases
      such as indigestion, constipation, chest fullness, chest pain, bronchitis, and
      sputum in Korea. P. trifoliata extract has recently been reported to possess
      anticancer properties; however, its mechanisms of action remain unclear. In this
      study, its antiproliferative effects and possible mechanisms were investigated in
      HSC-4 cells. The methanol extract of P. trifoliata (MEPT) significantly decreased
      the proliferation of HSC-4 cells (inhibitory concentration (IC)50 = 142.7 MUg/mL)
      in a dose-dependent manner. While there were no significant changes observed upon
      cell cycle analysis and ANNEXIN V and 7-AAD double staining in the MEPT-treated
      groups, the intensity of acidic vesicular organelle (AVO) staining and
      microtubule-associated protein 1 light chain (LC) 3-II protein expression
      increased in response to MEPT treatment. Furthermore, 3-methyladenine (3-MA,
      autophagy inhibitor) effectively blocked the MEPT-induced cytotoxicity of HSC-4
      cells and triggered the activation of p38 and extracellular signal-regulated
      kinases (ERK) proteins. Taken together, our results indicate that MEPT is a
      potent autophagy agonist in oral cancer cells with antitumor therapeutic
      potential that acts through the mitogen-activated protein kinase (MAPK) pathway. 

PMID- 26221174
TI  - Effects of RuPeng15 Powder (RPP15) on Monosodium Urate Crystal-Induced Gouty
      Arthritis in Rats.
AB  - RuPeng15 Powder (RPP15) is a herbal multicompound remedy that originates from
      traditional Tibetan medicine and possesses antigout, anti-inflammatory, and
      antihyperuricemic properties based on the traditional conceptions. The present
      study was undertaken to evaluate the therapeutic effect of PRP15 in rat gouty
      arthritis induced by monosodium urate (MSU) crystals. In the present study, we
      found that treatment with RPP15 (0.4, 0.8, and 1.2 g/kg) in rats with gouty
      arthritis induced by MSU crystals significantly attenuated the knee swelling.
      Histomorphometric and immunohistochemistry analyses revealed that MSU-induced
      inflammatory cell infiltration and the elevated expressions of nuclear
      transcription factor-kappaB p65 (NF-kappaB p65) in synovial tissues were
      significantly inhibited, and enzyme-linked immunosorbent assay (ELISA) result
      showed that MSU-induced high levels of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1beta), and interleukin-8 (IL-8) in synovial fluid were
      reduced by treatment with RPP15 (0.4, 0.8, and 1.2 g/kg). We conclude that RPP15
      may be a promising candidate for the development of a new treatment for gout and
      its activity of antigout may be partially related to inhibiting TNF-alpha, IL
      1beta, IL-8, and NF-kappaB p65 expression in the synovial tissues. 

PMID- 26221172
TI  - Rhein Elicits In Vitro Cytotoxicity in Primary Human Liver HL-7702 Cells by
      Inducing Apoptosis through Mitochondria-Mediated Pathway.
AB  - Objective. To study rhein-induced apoptosis signaling pathway and to investigate
      its molecular mechanisms in primary human hepatic cells. Results. Cell viability
      of HL-7702 cells treated with rhein showed significant decrease in dose-dependent
      manner. Following rhein treatment (25 MUM, 50 MUM, and 100 MUM) for 12 h, the
      detection of apoptotic cells was significantly analyzed by flow cytometry and
      nuclear morphological changes by Hoechst 33258, respectively. Fatty degeneration
      studies showed upregulation level of the relevant hepatic markers (P < 0.01).
      Caspase activities expressed significant upregulation of caspase-3, caspase-9,
      and caspase-8. Moreover, apoptotic cells by rhein were significantly inhibited by
      Z-LEHD-FMK and Z-DEVD-FMK, caspase-9 inhibitor, and caspase-3 inhibitor,
      respectively. Overproduction of reactive oxygen species, lipid peroxidation, and
      loss of mitochondrial membrane potential were detected by fluorometry.
      Additionally, NAC, a ROS scavenger, significantly attenuated rhein-induced
      oxidative damage in HL-7702 cells. Furthermore, real-time qPCR results showed
      significant upregulation of p53, PUMA, Apaf-1, and Casp-9 and Casp-3 mRNA, with
      no significant changes of Fas and Cytochrome-c. Immunoblotting revealed
      significant Cytochrome-c release from mitochondria into cytosol and no change in
      Fas expression. Conclusion. Taken together, these observations suggested that
      rhein could induce apoptosis in HL-7702 cells via mitochondria-mediated signal
      pathway with involvement of oxidative stress mechanism. 

PMID- 26221175
TI  - Integrated Treatment of Aqueous Extract of Solanum nigrum-Potentiated Cisplatin-
      and Doxorubicin-Induced Cytotoxicity in Human Hepatocellular Carcinoma Cells.
AB  - Chemotherapy is the main approach for treating advanced and recurrent
      hepatocellular carcinoma (HCC), but the clinical performance of chemotherapy is
      limited by a relatively low response rate, drug resistance, and adverse effects
      that severely affect the quality of life of patients. The aqueous extract of
      Solanum nigrum (AE-SN) is a crucial ingredient in some traditional Chinese
      medicine (TCM) formulas for treating cancer patients and exhibits antitumor
      effects in human HCC cells. Therefore, this study examined the tumor-suppression
      efficiency of AE-SN integrated with a standard chemotherapeutic drug, namely,
      cisplatin or doxorubicin, in human HCC cells, namely, Hep3B and HepJ5. The
      results suggested that the integrated treatment with AE-SN-potentiated cisplatin
      and doxorubicin induced cytotoxicity through the cleavage of caspase-7 and
      accumulation of microtubule-associated protein-1 light chain-3 A/1B II (LC-3 A/B
      II), which were associated with apoptotic and autophagic cell death,
      respectively, in both the Hep3B and HepJ5 cells. In conclusion, AE-SN can
      potentially be used in novel integrated chemotherapy with cisplatin or
      doxorubicin to treat HCC patients. 

PMID- 26221176
TI  - Intervening TNF-alpha via PPARgamma with Gegenqinlian Decoction in Experimental
      Nonalcoholic Fatty Liver Disease.
AB  - This paper is to explore the effect and mechanism of Gegenqinlian decoction on
      experimental nonalcoholic fatty liver disease (NAFLD) in vivo and in vitro. The
      final aim is to make clear whether Gegenqinlian decoction would impact NAFLD
      through improving PPARgamma to suppress inflammation and regulate lipid. The data
      in this research suggested that Gegenqinlian decoction is a potent way to manage
      NAFLD through improving PPARgamma to regulate lipid and suppress inflammation. 

PMID- 26221177
TI  - Hypoglycemic Effect of Ethanol and Ethyl Acetate Extract of Phellinus baumii
      Fruiting Body in Streptozotocin-Induced Diabetic Mice.
AB  - We investigated hypoglycemic effect of ethanol (EtOH) and ethyl acetate extract
      acetate (AcOEt) extracts in streptozotocin- (STZ-) induced diabetic mice. Our
      data showed the maximum inhibitory effect on the fasting plasma glucose (FPG)
      level was detected in STZ-induced diabetic mice administered with 400 mg/kg AcOEt
      extract of P. baumii. A lower glycated albumin (GA) level and a higher insulin
      level were observed in 400 mg/kg AcOEt and EtOH extract groups. Moreover, 400
      mg/kg AcOEt and EtOH extract exhibited a stronger effect on increasing size and
      cell number of islets. The insulin expression level of beta-cells and integrated
      optical density (IOD) value were significantly increased by the administration of
      400 mg/kg AcOEt and EtOH extracts. Taken together, AcOEt and EtOH extracts of P.
      baumii fruiting body exhibited considerable hypoglycemic effect on STZ-induced
      diabetic mice. 

PMID- 26221178
TI  - Antibacterial Effects and Mode of Action of Selected Essential Oils Components
      against Escherichia coli and Staphylococcus aureus.
AB  - Bacterial resistance has been increasingly reported worldwide and is one of the
      major causes of failure in the treatment of infectious diseases. Natural-based
      products, including plant secondary metabolites (phytochemicals), may be used to
      surpass or reduce this problem. The objective of this study was to determine the
      antibacterial effect and mode of action of selected essential oils (EOs)
      components: carveol, carvone, citronellol, and citronellal, against Escherichia
      coli and Staphylococcus aureus. The minimum inhibitory concentration (MIC) and
      minimum bactericidal concentration (MBC) were assessed for the selected EOs
      components. Moreover, physicochemical bacterial surface characterization,
      bacterial surface charge, membrane integrity, and K (+) leakage assays were
      carried out to investigate the antimicrobial mode of action of EOs components.
      Citronellol was the most effective molecule against both pathogens, followed by
      citronellal, carveol, and carvone. Changes in the hydrophobicity, surface charge,
      and membrane integrity with the subsequent K (+) leakage from E. coli and S.
      aureus were observed after exposure to EOs. This study demonstrates that the
      selected EOs have significant antimicrobial activity against the bacteria tested,
      acting on the cell surface and causing the disruption of the bacterial membrane.
      Moreover, these molecules are interesting alternatives to conventional
      antimicrobials for the control of microbial infections. 

PMID- 26221179
TI  - Plants Consumption and Liver Health.
AB  - The liver is a very important organ with a lot of functions for the host to
      survive. Dietary components are essential for and can be beneficial or
      detrimental to the healthy or diseased liver. Plants food is an essential part of
      the human diet and comprises various compounds which are closely related to liver
      health. Selected food plants can provide nutritional and medicinal support for
      liver disease. At the present, the knowledge of the effects of plants on the
      liver is still incomplete. The most urgent task at the present time is to find
      the best dietary and medicinal plants for liver health in an endless list of
      candidates. This review article updates the knowledge about the effects of plants
      consumption on the health of the liver, putting particular emphasis on the
      potential beneficial and harmful impact of dietary and medicinal plants on liver
      function. 

PMID- 26221180
TI  - The Effects of Acupuncture on Cerebral and Muscular Microcirculation: A
      Systematic Review of Near-Infrared Spectroscopy Studies.
AB  - Acupuncture produces physiological effects via stimulating acupoints, proximal or
      distal to the region of effect. Near-infrared spectroscopy (NIRS) noninvasively
      measures tissue-level hemodynamics in real time. We review the literature
      investigating the effect of acupuncture on muscular and/or cerebral
      microcirculation. As the basis, we queried PubMed in June 2014 for articles
      mentioning both acupuncture and NIRS in title/abstract. The reviewed papers
      investigated either cerebral (n = 11) or muscular hemodynamics (n = 5) and, based
      on STRICTA for reporting acupuncture methodology, were overall poor in quality.
      Acupuncture was found to influence regional oxygen saturation in cerebral and
      muscular tissue. The cortical response in healthy subjects varied across studies.
      For subjects with stroke or cerebrovascular dementia, findings suggest that
      acupuncture may modulate dysfunction in cerebral autoregulation. The muscular
      response to pressure techniques was more intense than that to needling or laser.
      Probe proximity could impact measurement sensitivity. No one study simultaneously
      investigated the direct and remote responses. Research utilizing NIRS to
      investigate the hemodynamics of acupuncture presently lacks in scope and quality.
      Improved designs, for example, placebo-controlled, randomized trials, and
      standardized intervention reporting will raise study quality. Exploiting NIRS in
      clinical settings, such as stroke, migraine, or other pain conditions, is
      worthwhile. 

PMID- 26221181
TI  - Electroacupuncture Ameliorates the Coronary Occlusion Related Tachycardia and
      Hypotension in Acute Rat Myocardial Ischemia Model: Potential Role of
      Hippocampus.
AB  - Mechanisms for electroacupuncture (EA) in disease treatments are still enigmatic.
      Here, we studied whether hippocampus was involved in the protection of EA
      stimulation on myocardial ischemia injury. Acute myocardial ischemia (AMI) model
      was produced. EA stimulation at heart meridian from Shenmen (HT7) to Tongli (HT5)
      was applied to rats 3 times a day for continuous three days. Coronary occlusion
      related tachycardia and hypotension, indicated by heart rate, mean arterial
      pressure, and rate pressure product, were apparently impaired after AMI injury.
      By contrast, EA stimulating could ameliorate the impairments of heart function (P
      < 0.05). Interestingly, lesion of CA1 region of hippocampus abolished the
      protection of EA. Neuronal activity in CA1 area was affected by AMI. As
      evidenced, cell counts, cell types, and frequency of the discharged neurons were
      facilitated after AMI, while EA stimulation attenuated the abnormalities.
      Furthermore, c-Fos expression was significantly facilitated in CA1 area after
      AMI, which was reduced by EA stimulation. Correlations were established between c
      Fos expression and cell counts of discharged neurons, as well as between heart
      function and cell counts of discharged neurons. Taken together, EA stimulation at
      heart meridian protects against heart dysfunction induced by AMI possibly through
      suppressing the neuronal activity in CA1 region. 

PMID- 26221182
TI  - Flavonoid Fraction of Orange and Bergamot Juices Protect Human Lung Epithelial
      Cells from Hydrogen Peroxide-Induced Oxidative Stress.
AB  - It has been reported that oxidant/antioxidant imbalance triggers cell damage that
      in turn causes a number of lung diseases. Flavonoids are known for their health
      benefits, and Citrus fruits juices are one of the main food sources of these
      secondary plant metabolites. The present study was designed to evaluate the
      effect of the flavonoid fraction of bergamot and orange juices, on H2O2-induced
      oxidative stress in human lung epithelial A549 cells. First we tested the
      antioxidant properties of both extracts in cell-free experimental models and then
      we assayed their capability to prevent the cytotoxic effects induced by H2O2. Our
      results demonstrated that both Citrus juice extracts reduce the generation of
      reactive oxygen species and membrane lipid peroxidation, improve mitochondrial
      functionality, and prevent DNA-oxidative damage in A549 cells incubated with
      H2O2. Our data indicate that the mix of flavonoids present in both bergamot and
      orange juices may be of use in preventing oxidative cell injury and pave the way
      for further research into a novel healthy approach to avoid lung disorders. 

PMID- 26221183
TI  - The Prioritization of Clinical Risk Factors of Obstructive Sleep Apnea Severity
      Using Fuzzy Analytic Hierarchy Process.
AB  - Recently, there has been a problem of shortage of sleep laboratories that can
      accommodate the patients in a timely manner. Delayed diagnosis and treatment may
      lead to worse outcomes particularly in patients with severe obstructive sleep
      apnea (OSA). For this reason, the prioritization in polysomnography (PSG)
      queueing should be endorsed based on disease severity. To date, there have been
      conflicting data whether clinical information can predict OSA severity. The 1,042
      suspected OSA patients underwent diagnostic PSG study at Siriraj Sleep Center
      during 2010-2011. A total of 113 variables were obtained from sleep
      questionnaires and anthropometric measurements. The 19 groups of clinical risk
      factors consisting of 42 variables were categorized into each OSA severity. This
      study aimed to array these factors by employing Fuzzy Analytic Hierarchy Process
      approach based on normalized weight vector. The results revealed that the first
      rank of clinical risk factors in Severe, Moderate, Mild, and No OSA was nighttime
      symptoms. The overall sensitivity/specificity of the approach to these groups was
      92.32%/91.76%, 89.52%/88.18%, 91.08%/84.58%, and 96.49%/81.23%, respectively. We
      propose that the urgent PSG appointment should include clinical risk factors of
      Severe OSA group. In addition, the screening for Mild from No OSA patients in
      sleep center setting using symptoms during sleep is also recommended (sensitivity
      = 87.12% and specificity = 72.22%). 

PMID- 26221184
TI  - Construction of BAC contig maps of homoeologous chromosomes A12 and D12 of
      Gossypium hirsutum L. acc. TM-1.
AB  - BACKGROUND: The Gossypium hirsutum homoeologous chromosome 12 encodes important
      genes that contribute to fiber fuzz, lethality, gland development and male
      sterility. In this study a physical map of the cotton TM-1 chromosome 12 was
      constructed. A number of large-insert cotton genome libraries are available, and
      genome-wide physical mapping using large insert segments combined with bacterial
      cloning is a thriving area of genome research. However, sequencing of the cotton
      genome is difficult due to sequence repeats and homoeologous regions. In order to
      effectively distinguish the homologous segments, a new method for adjusting the
      parameters of the FPC software was applied for contig map construction. RESULTS:
      All available markers on chromosomes A12 and D12 were used to screen the TM-1 BAC
      library by PCR. A total of 775 clones (387 for A12, 388 for D12) were obtained
      using Hind III fingerprinting and used for construction of the contig map. Seven
      pairs of SSR markers located on A12 and D12 were chosen for contig analysis.
      Following optimization of the tolerance (10) and cutoff (1e-12) parameters,
      combining all clones from A12 and D12 produced two separate contigs. CONCLUSIONS:
      The BAC contig map of chromosomes A12 and D12 was constructed and FPC software
      parameters were optimized for analysis. The resulting approach is a powerful
      platform for genome-wide and evolutionary research on cotton.

PMID- 26221187
TI  - From genes to genomes in the clinic.
AB  - Next-generation sequencing is revolutionizing medical genetics and in the near
      future will pervade all medical fields. To maximize the potential clinical
      utility of this approach, global data sharing and phenotyping are needed, and the
      role of the geneticist in the interpretation of variation is vital. 

PMID- 26221185
TI  - The oxidative demethylase ALKBH3 marks hyperactive gene promoters in human cancer
      cells.
AB  - BACKGROUND: The oxidative DNA demethylase ALKBH3 targets single-stranded DNA
      (ssDNA) in order to perform DNA alkylation damage repair. ALKBH3 becomes
      upregulated during tumorigenesis and is necessary for proliferation. However, the
      underlying molecular mechanism remains to be understood. METHODS: To further
      elucidate the function of ALKBH3 in cancer, we performed ChIP-seq to investigate
      the genomic binding pattern of endogenous ALKBH3 in PC3 prostate cancer cells
      coupled with microarray experiments to examine the expression effects of ALKBH3
      depletion. RESULTS: We demonstrate that ALKBH3 binds to transcription associated
      locations, such as places of promoter-proximal paused RNA polymerase II and
      enhancers. Strikingly, ALKBH3 strongly binds to the transcription initiation
      sites of a small number of highly active gene promoters. These promoters are
      characterized by high levels of transcriptional regulators, including
      transcription factors, the Mediator complex, cohesin, histone modifiers, and
      active histone marks. Gene expression analysis showed that ALKBH3 does not
      directly influence the transcription of its target genes, but its depletion
      induces an upregulation of ALKBH3 non-bound inflammatory genes. CONCLUSIONS: The
      genomic binding pattern of ALKBH3 revealed a putative novel hyperactive promoter
      type. Further, we propose that ALKBH3 is an intrinsic DNA repair protein that
      suppresses transcription associated DNA damage at highly expressed genes and
      thereby plays a role to maintain genomic integrity in ALKBH3-overexpressing
      cancer cells. These results raise the possibility that ALKBH3 may be a potential
      target for inhibiting cancer progression.

PMID- 26221186
TI  - Prospective participant selection and ranking to maximize actionable
      pharmacogenetic variants and discovery in the eMERGE Network.
AB  - BACKGROUND: In an effort to return actionable results from variant data to
      electronic health records (EHRs), participants in the Electronic Medical Records
      and Genomics (eMERGE) Network are being sequenced with the targeted
      Pharmacogenomics Research Network sequence platform (PGRNseq). This cost
      effective, highly-scalable, and highly-accurate platform was created to explore
      rare variation in 84 key pharmacogenetic genes with strong drug phenotype
      associations. METHODS: To return Clinical Laboratory Improvement Amendments
      (CLIA) results to our participants at the Group Health Cooperative, we sequenced
      the DNA of 900 participants (61 % female) with non-CLIA biobanked samples. We
      then selected 450 of those to be re-consented, to redraw blood, and ultimately to
      validate CLIA variants in anticipation of returning the results to the
      participant and EHR. These 450 were selected using an algorithm we designed to
      harness data from self-reported race, diagnosis and procedure codes, medical
      notes, laboratory results, and variant-level bioinformatics to ensure selection
      of an informative sample. We annotated the multi-sample variant call format by a
      combination of SeattleSeq and SnpEff tools, with additional custom variables
      including evidence from ClinVar, OMIM, HGMD, and prior clinical associations.
      RESULTS: We focused our analyses on 27 actionable genes, largely driven by the
      Clinical Pharmacogenetics Implementation Consortium. We derived a ranking system
      based on the total number of coding variants per participant (75.2+/-14.7), and
      the number of coding variants with high or moderate impact (11.5+/-3.9). Notably,
      we identified 11 stop-gained (1 %) and 519 missense (20 %) variants out of a
      total of 1785 in these 27 genes. Finally, we prioritized variants to be returned
      to the EHR with prior clinical evidence of pathogenicity or annotated as stop
      gain for the following genes: CACNA1S and RYR1 (malignant hyperthermia); SCN5A,
      KCNH2, and RYR2 (arrhythmia); and LDLR (high cholesterol). CONCLUSIONS: The
      incorporation of genetics into the EHR for clinical decision support is a complex
      undertaking for many reasons including lack of prior consent for return of
      results, lack of biospecimens collected in a CLIA environment, and EHR
      integration. Our study design accounts for these hurdles and is an example of a
      pilot system that can be utilized before expanding to an entire health system.

PMID- 26221188
TI  - Global genetic carrier testing: a vision for the future.
AB  - Expanded genetic carrier testing is changing clinical practice. Current
      experience highlights the need for rigorous curation of tens of thousands of
      variants as to their pathogenicity and phenotypic effects. There is an urgent
      need for strategies to present a range of options to families to enable them to
      make informed decisions. The potential exists to avoid the great majority of
      serious inherited, but not de novo, single-gene disabilities. 

PMID- 26221189
TI  - Next-generation sequencing to guide cancer therapy.
AB  - As a result of multiple technological and practical advances, high-throughput
      sequencing, known more commonly as "next-generation" sequencing (NGS), can now be
      incorporated into standard clinical practice. Whereas early protocols relied on
      samples that were harvested outside of typical clinical pathology workflows,
      standard formalin-fixed, paraffin-embedded specimens can more regularly be used
      as starting materials for NGS. Furthermore, protocols for the analysis and
      interpretation of NGS data, as well as knowledge bases, are being amassed,
      allowing clinicians to act more easily on genomic information at the point of
      care for patients. In parallel, new therapies that target somatically mutated
      genes identified through clinical NGS are gaining US Food and Drug Administration
      (FDA) approval, and novel clinical trial designs are emerging in which genetic
      identifiers are given equal weight to histology. For clinical oncology providers,
      understanding the potential and the limitations of DNA sequencing will be crucial
      for providing genomically driven care in this era of precision medicine. 

PMID- 26221190
TI  - Targeted next-generation sequencing reveals high frequency of mutations in
      epigenetic regulators across treatment-naive patient melanomas.
AB  - BACKGROUND: Recent developments in genomic sequencing have advanced our
      understanding of the mutations underlying human malignancy. Melanoma is a
      prototype of an aggressive, genetically heterogeneous cancer notorious for its
      biologic plasticity and predilection towards developing resistance to targeted
      therapies. Evidence is rapidly accumulating that dysregulated epigenetic
      mechanisms (DNA methylation/demethylation, histone modification, non-coding RNAs)
      may play a central role in the pathogenesis of melanoma. Therefore, we sought to
      characterize the frequency and nature of mutations in epigenetic regulators in
      clinical, treatment-naive, patient melanoma specimens obtained from one academic
      institution. RESULTS: Targeted next-generation sequencing for 275 known and
      investigative cancer genes (of which 41 genes, or 14.9 %, encoded an epigenetic
      regulator) of 38 treatment-naive patient melanoma samples revealed that 22.3 %
      (165 of 740) of all non-silent mutations affected an epigenetic regulator. The
      most frequently mutated genes were BRAF, MECOM, NRAS, TP53, MLL2, and CDKN2A. Of
      the 40 most commonly mutated genes, 12 (30.0 %) encoded epigenetic regulators,
      including genes encoding enzymes involved in histone modification (MECOM, MLL2,
      SETD2), chromatin remodeling (ARID1B, ARID2), and DNA methylation and
      demethylation (TET2, IDH1). Among the 38 patient melanoma samples, 35 (92.1 %)
      harbored at least one mutation in an epigenetic regulator. The genes with the
      highest number of total UVB-signature mutations encoded epigenetic regulators,
      including MLL2 (100 %, 16 of 16) and MECOM (82.6 %, 19 of 23). Moreover, on
      average, epigenetic genes harbored a significantly greater number of UVB
      signature mutations per gene than non-epigenetic genes (3.7 versus 2.4,
      respectively; p = 0.01). Bioinformatics analysis of The Cancer Genome Atlas
      (TCGA) melanoma mutation dataset also revealed a frequency of mutations in the 41
      epigenetic genes comparable to that found within our cohort of patient melanoma
      samples. CONCLUSIONS: Our study identified a high prevalence of somatic mutations
      in genes encoding epigenetic regulators, including those involved in DNA
      demethylation, histone modification, chromatin remodeling, and microRNA
      processing. Moreover, UVB-signature mutations were found more commonly among
      epigenetic genes than in non-epigenetic genes. Taken together, these findings
      further implicate epigenetic mechanisms, particularly those involving the
      chromatin-remodeling enzyme MECOM/EVI1 and histone-modifying enzyme MLL2, in the
      pathobiology of melanoma.

PMID- 26221191
TI  - DNA methylation signature in peripheral blood reveals distinct characteristics of
      human X chromosome numerical aberrations.
AB  - BACKGROUND: Abnormal sex chromosome numbers in humans are observed in Turner
      (45,X) and Klinefelter (47,XXY) syndromes. Both syndromes are associated with
      several clinical phenotypes, whose molecular mechanisms are obscure, and show a
      range of inter-individual penetrance. In order to understand the effect of
      abnormal numbers of X chromosome on the methylome and its correlation to the
      variable clinical phenotype, we performed a genome-wide methylation analysis
      using MeDIP and Illumina's Infinium assay on individuals with four karyotypes:
      45,X, 46,XY, 46,XX, and 47,XXY. RESULTS: DNA methylation changes were widespread
      on all autosomal chromosomes in 45,X and in 47,XXY individuals, with Turner
      individuals presenting five times more affected loci. Differentially methylated
      CpGs, in most cases, have intermediate methylation levels and tend to occur
      outside CpG islands, especially in individuals with Turner syndrome. The X
      inactivation process appears to be less effective in Klinefelter syndrome as
      methylation on the X was decreased compared to normal female samples. In a large
      number of individuals, we verified several loci by pyrosequencing and observed
      only weak inter-loci correlations between the verified regions. This suggests a
      certain stochastic/random contribution to the methylation changes at each locus.
      Interestingly, methylation patterns on some PAR2 loci differ between male and
      Turner syndrome individuals and between female and Klinefelter syndrome
      individuals, which possibly contributed to this distinguished and unique
      autosomal methylation patterns in Turner and Klinefelter syndrome individuals.
      CONCLUSIONS: The presented data clearly show that gain or loss of an X chromosome
      results in different epigenetic effects, which are not necessary opposite.

PMID- 26221193
TI  - Canadian Urological Association - Association des urologues du Canada 70(th)
      Annual Meeting - Ottawa, ON - June 27-30, 2015.

PMID- 26221192
TI  - Probiotics and immunity: provisional role for personalized diets and disease
      prevention.
AB  - There is great interest in the interaction between diet and immune system and
      concomitantly in the potential of probiotic bacteria, especially given recent
      advances in understanding of gut microbiota effects on health in the context of
      microbiome research. Following our recent study on bacterial wall elasticity as a
      predictive measure of phagocytic cellular reactions and related outcomes, a
      question was raised regarding the scope of the application of these findings in
      various medical conditions in the context of predictive, preventive, and
      personalized medicine (PPPM). This summarizing review of the data describes the
      contributions, both observed and potential, of probiotics to the gut-brain axis
      and various medical conditions, including immune and atopic states, metabolic and
      inflammatory diseases-including liver disease and diabetes mellitus-cancer, and
      more. It also suggests novel insights for a number of beneficial applications of
      probiotics and advances in development of novel probiotic-based treatments and
      personalized diets, as well as application of sophisticated imaging techniques
      and nanobiotechnologies that can be adopted in the near future by innovative
      medical experts, warranting further research and practical translation. 

PMID- 26221195
TI  - What's New in Renal Cell Cancer Research? Highlights of GU-ASCO 2015.

PMID- 26221194
TI  - What's New in Prostate Cancer Research? Highlights of GU-ASCO 2015.

PMID- 26221196
TI  - Biochemical perturbations of the mitotic spindle in Xenopus extracts using a
      diffusion-based microfluidic assay.
AB  - A microfluidic device is a powerful tool to manipulate in a controlled manner at
      spatiotemporal scales for biological systems. Here, we describe a simple
      diffusion-based assay to generate and measure the effect of biochemical
      perturbations within the cytoplasm of cell-free extracts from Xenopus eggs. Our
      approach comprises a microliter reservoir and a model cytoplasm that are
      separated by a synthetic membrane containing sub-micrometric pores through which
      small molecules and recombinant proteins can diffuse. We have used this system to
      examine the perturbation of elements of the mitotic spindle, which is a
      microtubule-based bipolar structure involved in the segregation of the replicated
      genome to daughter cells during cell division. First, we used the small molecule
      inhibitor monastrol to target kinesin-5, a molecular motor that maintains the
      microtubule spindle bipolarity. Next, we explored the dynamics of the mitotic
      spindle by monitoring the exchange between unpolymerized and polymerized tubulin
      within microtubule fibers. These results show that a simple diffusion-based
      system can generate biochemical perturbations directly within a cell-free
      cytoplasm based on Xenopus egg extracts at the time scale of minutes. Our assay
      is therefore suitable for monitoring the dynamics of supramolecular assemblies
      within cell-free extracts in response to perturbations. This strategy opens up
      broad perspectives including phenotype screening or mechanistic studies of
      biological assembly processes and could be applied to other cell-free extracts
      such as those derived from mammalian or bacterial cells. 

PMID- 26221197
TI  - Simultaneous diamagnetic and magnetic particle trapping in ferrofluid microflows
      via a single permanent magnet.
AB  - Trapping and preconcentrating particles and cells for enhanced detection and
      analysis are often essential in many chemical and biological applications.
      Existing methods for diamagnetic particle trapping require the placement of one
      or multiple pairs of magnets nearby the particle flowing channel. The strong
      attractive or repulsive force between the magnets makes it difficult to align and
      place them close enough to the channel, which not only complicates the device
      fabrication but also restricts the particle trapping performance. This work
      demonstrates for the first time the use of a single permanent magnet to
      simultaneously trap diamagnetic and magnetic particles in ferrofluid flows
      through a T-shaped microchannel. The two types of particles are preconcentrated
      to distinct locations of the T-junction due to the induced negative and positive
      magnetophoretic motions, respectively. Moreover, they can be sequentially
      released from their respective trapping spots by simply increasing the ferrofluid
      flow rate. In addition, a three-dimensional numerical model is developed, which
      predicts with a reasonable agreement the trajectories of diamagnetic and magnetic
      particles as well as the buildup of ferrofluid nanoparticles. 

PMID- 26221199
TI  - Microfluidic reflow pumps.
AB  - A new microfluidic pump, termed a reflow pump, is designed to operate with a sub
      MUl sample volume and transport it back and forth between two pneumatically
      actuated reservoirs through a flow channel typically containing one or more
      sensor surfaces. The ultimate motivation is to efficiently use the small sample
      volume in conjunction with convection to maximize analyte flux to the sensor
      surface(s) in order to minimize sensor response time. In this paper, we focus on
      the operational properties of the pumps themselves (rather than the sensor
      surfaces), and demonstrate both two-layer and three-layer polydimethylsiloxane
      reflow pumps. For the three-layer pump, we examine the effects of reservoir
      actuation pressure and actuation period, and demonstrate average volumetric flow
      rates as high as 500 MUl/min. We also show that the two-layer design can pump up
      to 93% of the sample volume during each half period and demonstrate integration
      of a reflow pump with a single-chip microcantilever array to measure maximum flow
      rate. 

PMID- 26221198
TI  - DNA-library assembly programmed by on-demand nano-liter droplets from a custom
      microfluidic chip.
AB  - Nanoscale synthetic biology can benefit from programmable nanoliter-scale
      processing of DNA in microfluidic chips if they are interfaced effectively to
      biochemical arrays such as microwell plates. Whereas active microvalve chips
      require complex fabrication and operation, we show here how a passive and readily
      fabricated microchip can be employed for customizable nanoliter scale pipetting
      and reaction control involving DNA. This recently developed passive microfluidic
      device, supporting nanoliter scale combinatorial droplet generation and mixing,
      is here used to generate a DNA test library with one member per droplet exported
      to addressed locations on microwell plates. Standard DNA assembly techniques,
      such as Gibson assembly, compatible with isothermal on-chip operation, are
      employed and checked using off-chip PCR and assembly PCR. The control of output
      droplet sequences and mixing performance was verified using dyes and
      fluorescently labeled DNA solutions, both on-chip and in external capillary
      channels. Gel electrophoresis of products and DNA sequencing were employed to
      further verify controlled combination and functional enzymatic assembly. The
      scalability of the results to larger DNA libraries is also addressed by
      combinatorial input expansion using sequential injection plugs from a multiwell
      plate. Hence, the paper establishes a proof of principle of the production of
      functional combinatorial mixtures at the nanoliter scale for one sequence per
      well DNA libraries. 

PMID- 26221200
TI  - Utilization of Platelet-Rich Plasma for a Fistula With Subcutaneous Cavity
      Following Septic Bursitis: A Case Report.
AB  - In platelet-rich plasma (PRP) therapy, various growth factors and cytokines
      released the alpha-granules contained in platelets after activation can
      potentially enhance wound healing by delivering. We report a patient in whom
      treatment with PRP, prepared using a syringe-centrifugation-system PRP kit
      (KYOCERA Medical PRP Kit), for a fistula following bursitis of the lateral
      malleolus, which could not be healed with conventional wound therapy, led to
      successful healing. A 58-year-old man was on dialysis for type II diabetes and
      chronic renal failure. In the left lateral malleolus, septic bursitis developed,
      leading to a refractory fistula with a subcutaneous cavity measuring 4 * 3 cm,
      which persisted for more than 2 months. Platelet-rich plasma was prepared using
      the KYOCERA Medical PRP Kit (KYOCERA Medical Corporation, Osaka, Japan) and
      infused into the cavity twice to close it. After this procedure, the cavity size
      reduced, but the orifice and subcutaneous cavity were not closed. Therefore,
      additional PRP therapy was conducted after 10 weeks of the first PRP session.
      Complete closure was achieved 13 weeks after the first PRP therapy. In the
      present case, PRP was prepared using the KYOCERA Medical PRP Kit, and wound
      healing of a fistula with subcutaneous cavity following bursitis of the lateral
      malleolus was successfully cured. The KYOCERA Medical PRP Kit was useful, because
      PRP could be prepared simply and inexpensively using the syringe-centrifugation
      system. 

PMID- 26221202
TI  - GSTT1 polymorphism and breast cancer risk in the Chinese population: an updated
      meta-analysis and review.
AB  - BACKGROUND: Although a number of studies have been conducted on the association
      between GSTT1 polymorphism and breast cancer in China, this association remains
      elusive and controversial. To clarify the effects of GSTT1 polymorphism on the
      risk of breast cancer, an updated meta-analysis was performed in the Chinese
      population. MATERIAL/METHODS: Related studies were identified from PubMed,
      Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese
      National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) to
      up 28(th) January 2015. Pooled ORs and 95% CIs were used to assess the strength
      of the associations. RESULTS: A total of 13 studies including 3387 breast cancer
      cases and 5085 controls were involved in this meta-analysis. Overall, a
      significant association (OR = 1.31, 95% CI: 1.02-1.67) was found between the null
      GSTT1 and breast cancer risk when all studies in Chinese population pooled into
      the meta-analysis. In subgroup analyses stratified by geographic areas and source
      of controls, it revealed the significant results in population-based studies (OR
      = 1.42, 95% CI: 1.23-1.65) and South China (OR = 1.47, 95% CI: 1.27-1.70).
      CONCLUSIONS: This meta-analysis showed that the null GSTT1 may be potential
      biomarkers for breast cancer risk in Chinese, and further studies with gene-gene
      and gene-environment interactions are required for definite conclusions.

PMID- 26221201
TI  - Association between PNPLA3 rs738409 polymorphisms and risk of hepatocellular
      carcinoma and its development in patients with cirrhosis: a meta-analysis.
AB  - Genetic variants of PNPLA3 have been implicated in hepatocellular carcinoma (HCC)
      susceptibility; however, published findings have been both conflicting and
      inconclusive. To obtain a more precise estimate of the association of the PNPLA3
      rs738409 (C > G) polymorphism with the overall risk of HCC and in patients with
      cirrhosis, we performed a meta-analysis of nine eligible studies identified
      through an online search of Ovid, PubMed, EBSCO, the Cochrane Library, the Web of
      Science, the China National Knowledge Infrastructure, Wanfang, and Chinese
      Biomedicine databases. The studies comprised 1175 patients with HCC, 876 with
      cirrhosis, and 3026 healthy controls. Pooled odds ratios (ORs) with corresponding
      95% confidence intervals (CIs) were calculated to assess associations, using
      fixed-effects models. Etiology subgroup and sensitivity analyses were also
      performed. Our results showed that rs738409 was associated with overall HCC risk
      and in patients with cirrhosis in the genetic contrast modes: G vs. C, GG + CG
      vs. CC, GG vs. CG + GG, and GG vs. CC. Stratification by etiology did not reveal
      any significant association between this polymorphism and hepatitis C virus (HCV)
      related HCC in patients with HCV-related cirrhosis (P > 0.05). However, healthy
      individuals harboring two copies of the rs738409 G variant had a higher risk of
      HCC (GG vs. CC: OR = 4.40, 95% CI: 3.28-5.91) than those carrying a single G
      allele (CG vs. CC: OR = 1.62, 95% CI: 1.34-1.59); these significant association
      were also present in each subgroup. Furthermore, the association was more
      pronounced in alcohol vs. HCV-related HCC. The present meta-analysis suggests
      that the PNPLA3 rs738409 G allele is a risk factor for HCC except in patients
      with HCV-related cirrhosis, and that two copies of the rs738409 G variant
      conferred a higher risk for HCC in controls, especially for alcohol-related HCC.
      Further studies with a larger sample size are needed to ascertain the association
      in different ethnicities. 

PMID- 26221203
TI  - Critical analysis of the correlation between optical coherence tomography versus
      intravascular ultrasound and fractional flow reserve in the management of
      intermediate coronary artery lesion.
AB  - The appropriate assessment of intermediate coronary artery stenosis continues to
      be a challenge for cardiologists. Several studies have shown that anatomic
      parameters obtained by intravascular ultrasound (IVUS) and optical coherence
      tomography (OCT) showed a correlation with fractional flow reserve (FFR) values
      in identifying hemodynamically severe coronary stenoses. However, the efficacy of
      IVUS/OCT versus FFR integration in intermediate coronary lesions is still
      debated. This review will allow for an independent analysis of research data and
      outlines the diagnostic efficiency of IVUS and OCT derived-anatomical parameters
      in identifying the hemodynamic significance of an angiographically intermediate
      stenosis as determined by FFR. 

PMID- 26221204
TI  - Speckle tracking echocardiography: clinical applications in cardiac
      resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) is a proven therapy for selected patients
      with heart failure, it has been shown to improve symptoms and left ventricular
      (LV) function and prolong survival. Despite proven benefit of CRT, a significant
      proportion of patients fail to respond to CRT. Multiple factors contribute to the
      non-response such as patient selection and device implantation including LV lead
      placement. Speckle tracking echocardiography (STE) derived strain imaging offers
      detailed characterization of LV function and provides indices of mechanical
      dyssynchrony, in addition, STE systolic strain could be used to identify area of
      scar, therefore applications of STE-derived strain imaging in CRT warrant a
      closer inspection. This review considers and summarizes different indices of
      mechanical dyssynchrony generated by STE-derived strain imaging and their
      relevance in patient selection for CRT and their prognostic values in predicting
      response to CRT. This review further examines applications of STE-derived strain
      imaging in optimizing LV lead position by detecting site of latest mechanical
      activation and presence or absence of transmural scar in a particular segment. 

PMID- 26221205
TI  - Thyroid dysfunction: an autoimmune aspect.
AB  - Auto immune thyroid disease (AITD) is the common organ specific autoimmune
      disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known
      sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase
      (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which
      leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis
      (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the
      gland. Presences of TPO antibodies are common in HT and GD, while Tg has been
      reported as an independent predictor of thyroid malignancy. Cytokines are small
      proteins play an important role in autoimmunity, by stimulating B and T cells.
      Various cytokines IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL
      13, IL-14, TNF-alpha and IFN-gamma are found in thyroid follicular cells which
      enhance inflammatory response with nitric oxide (NO) and prostaglandins. 

PMID- 26221206
TI  - Positive emotion and cardiovascular disease in elderly people.
AB  - Cardiovascular disease in elderly people is a psychosomatic disease, but the
      research on the relationship between positive emotion and cardiovascular diseases
      is few. Most previous studies have focused on a range of health status changes
      caused by negative emotion but have ignored the role of positive emotion in
      elderly people. Positive emotion has been considered a protective factor against
      health problems in elderly people. Research shows that a significant relationship
      between positive emotion and blood pressure remains after adjusting for
      depression in elderly people. In this paper, we summarize the relationship
      between positive emotion and cardiovascular diseases in elderly people. 

PMID- 26221208
TI  - Neuregulin protects human umbilical vein endothelial cell via activating CD98hc
      through MAPK pathway.
AB  - BACKGROUND: To study the effects of neuregulin on human umbilical vein
      endothelial cells (HUVEC) protection. METHODS: The HUEVC were cultured and
      divided into three different groups according to their culture conditions. In
      negative control group (group A), HUVEC were cultured in dulbecco modified eagle
      medium (DMEM) supplemented with 25 mmol/L glucose and neuregulin (10 ng/ml, 100
      ng/ml, and 1000 ng/ml, respectively) for 48 hr. In experimental group (group B),
      HUVEC were cultured in DMEM with 75 mmol/L glucose and neuregulin (10 ng/ml, 100
      ng/ml, and 1000 ng/ml, respectively) for 48 hr. In positive control group (group
      C), HUVEC were cultured in DMEM supplemented with 75 mmol/L mannitol, 25 mmol/L
      glucose, and neuregulin (10 ng/ml, 100 ng/ml, and 1000 ng/ml, respectively) for
      48 hr. This study aimed to observe the cell morphology in different HUEVC groups
      and analyze apoptosis in each group via characterizing and detecting the protein
      expressions of CD98hc, p38, and JNK. RESULTS: Significant differences in cell
      morphology were observed in the experimental group when compared with the control
      groups. In the experimental group, the degree of apoptosis was negatively related
      to the neuregulin concentration; CD98hc protein concentration was positively
      related to neuregulin concentration; JNK protein concentration was positively
      related to neuregulin concentration. However, there was no significant
      relationship between p38 protein expression and the concentration of glucose in
      the medium. CONCLUSION: Neuregulin could inhibit the apoptosis of HUEVC through
      the activation of MAPK signaling pathway via activating CD98hc expression.

PMID- 26221207
TI  - Reversing drug resistance of cisplatin by hsp90 inhibitors in human ovarian
      cancer cells.
AB  - OBJECTIVE: To investigate the mechanisms for reversing drug resistance of
      cisplatin (DDP) by Hsp90 inhibitors (geldanamycin (GA), 17-AAG, 17-DMAG) in human
      ovarian cancer. METHODS: Cell proliferation rate in DDP resistant human ovarian
      cancer cell line SKOV3/DDP and its parent cell line SKOV3 after treatment with
      Hsp90 inhibitors and/or DDP were tested by MTT assay, and the reversing fold (RF)
      of DDP by Hsp90 inhibitors was calculated. Cell cycle and cell apoptosis status
      after treatment were analyzed by flow cytometry. The expression of multiple drug
      resistance related genes was analyzed by RT-PCR and Western-blot. RESULTS: All
      three tested Hsp90 inhibitors synergistically inhibited the cell proliferation of
      SKOV3 with DDP and enhanced the sensitivity of SKOV3/DDP cells to DDP. The RF of
      DDP by Hsp90 inhibitors were all more than two fold. GA caused cell cycle arrest
      in G2/M phasein SKOV3 cells. 17-AAG increased cell apoptosis but did not change
      cell cycle in SKOV3/DDP cells. The mRNA and protein expression levels of various
      drug resistant related genes including LRP, GST-pi, p53, bcl-2, survivin, ERCC1,
      XRCC1, BRCA1 and BRCA2 were more dramatically altered by Hsp90 inhibitors and DDP
      in combination compared to Hsp90 inhibitors or DDP treatment alone. CONCLUSIONS:
      Exposure of SKOV3/DDP cells to Hsp90 inhibitors and DDP in combination results in
      synergistic cytotoxic and pro-apoptotic effects. Hsp90 inhibitors reverse the
      drug resistance of SKOV3/DDP cells to DDP by modifying the expression of multiple
      drug resistance related genes.

PMID- 26221209
TI  - Efficient differentiation of neural stem cells induced by the rat bone marrow
      stromal cells.
AB  - Neural stem cells (NSCs) are valuable self-renewing cells that can maintain the
      capacity to differentiate into specific brain cell types. NSCs may repair and
      even replace the brain tissue, and ultimatley promoting the central nervous
      system regeneration. Therefore, it is important, for scientists and pjysicians,
      to study the method for efficient culture and differentiation of NSCs. Our
      previous study demonstrated that Bone Marrow Stromal Cells (BMSCs) can directly
      regulate the differentiation of NSCs into neurons, and soluble molecules excreted
      by BMSCs played a key role in this process. Hereby, we further identified the
      BMSCs-induced neurons could form the synapses, convey dopamine and express
      voltage-depend and receptor-depend calcium channels. Moreover, the extracellular
      signal-regulated protein kinase ERK1/2 pathway was founded to be involved in the
      process of neuron differentiation and proliferation by the in vitro experiments.
      Finally, by using protein array, we, for the first time, found that the cytokine
      induced neutrophil chemoattractant-3 (CINC-3, a small molecule cytokine) can
      promote the leukocytes invasion into the inflammation site, and have the ability
      to induce mesencephal NSCs into neurons. Consequently, these positive findings
      suggested that our BMSCs-induced culture system could provide a useful tool to
      investigate the molecular mechanisms of neural differentiation of NSCs, which may
      be benifical for neurodegenerative diseases in the near future. 

PMID- 26221210
TI  - Silencing the NR2B gene in rat ACC neurons by lentivirus-delivered shRNA
      alleviates pain-related aversion.
AB  - The N-methyl-D-aspartate (NMDA) receptor NR2B subunit on neurons in the anterior
      cingulate cortex (ACC) is implicated in the affective response to noxious
      stimuli. Selectively silencing this NR2B subunit in ACC neurons could therefore
      alleviate pain-related aversion. However, to date, there is no optimal approach
      to selectively silence the NR2B gene in ACC neurons. In the present study, we
      constructed lentiviral vectors and delivered shRNA (NR2B-RNAi-LV) to effectively
      silence the NR2B gene in ACC neurons. The use of lentivirus resulted in 95%
      transfection efficiency and 83% silencing of the NR2B gene in ACC neurons.
      Electrophysiological experiments showed that the total INMDA was similarly
      reduced by 48% in lentivirus-transfected ACC neurons. The biochemical and
      functional data demonstrated that lentiviral shRNA delivery produced a high
      transfection and silencing efficiency in the ACC neurons. SNI rats weighting 220
      250 g were randomly divided into three groups: normal saline group (NS), lenti
      siRNA/NC (LV-NC) group, and lenti-siRNA/NR2B (LV-NR2B) group, and conditioned
      place avoidance was conducted. The results indicated that NR2B-RNAi-LV decreased
      greatly the conditioning scores of F-CPA while NC-GFP-LV has no effects. NR2B
      mRNA expression in the NR2B-RNAi-LV group was significantly lower than that in
      the control group and NC-GFP-LV group. This novel approach of silencing the NR2B
      gene in ACC neuron could potentially be used to alleviate pain-related aversion. 

PMID- 26221211
TI  - Investigation on effects of the nourishing kidney and eliminating toxicity
      decoction on immunological imbalance of Th1, Th17 and Treg in HBV transgenic
      mice.
AB  - OBJECTIVE: To study the immune mechanism of nourishing kidney and eliminating
      toxicity decoction (NKETD) on Chronic Hepatitis B (CHB), we detected the serum
      concentrations of IFN-gamma (the characteristic cytokine of Th1), IL-17A (the
      characteristic cytokine of Th17) and the quantitative proportion of CD(+) 4CD(+)
      25 foxp3 Treg to CD(+) 4 Treg in HBV transgenic mice. METHODS: The HBV transgenic
      mice were randomly divided into six groups: high-dose group, middle-dose group,
      low-dose group, lamivudine group, model control group and normal mice control
      group. The serum concentrations of IFN-gamma and IL-17A in mice were measured by
      ELISA method and the ratio of CD(+) 4CD(+) 25 foxp3 Treg to CD(+) 4 Treg was
      detected by Flow Cytometry Method (FCM). RESULTS: The decoction could increase
      the serum concentration of IFN-gamma and decrease that of IL-17A in HBV
      transgenic mice. The higher the dose was, the more significantly the
      concentration of IFN-gamma increased. And high-dose decoction could decrease the
      serum concentration of IL-17A in HBV transgenic mice significantly and
      continuously while middle-dose and low-dose decoction had no significant effects.
      However, there wasn't statistically significant variation on the ratio of CD(+)
      4CD(+) 25 foxp3 Treg to CD(+) 4 Treg in HBV transgenic mice. CONCLUSION: The
      decoction could treat CHB by regulating the immune function by promoting the
      generation of Th1 and/or enhancing its function while inhibiting Th17. The immune
      regulation by decoction had more significant effects than lamivudine.

PMID- 26221212
TI  - A meta-analysis of the antitumor effect and safety of bisphosphonates in the
      treatment of multiple myeloma.
AB  - BACKGROUND: The objective of this meta-analysis was to determine the
      effectiveness and safety of bisphosphonates (BPs) for patients with multiple
      myeloma (MM). METHODS: The study included patients with MM, who were randomly
      allocated to receive either BPs or control. PubMed/Medline, Embase, the Cochrane
      Database of Systematic Reviews (CDSR), and the Cochrane Central Register of
      Controlled Trials were searched up to January 2014, and only published trials
      were included in the analysis. There was no language restriction. The results
      were analyzed using RevMan 5.2 software, which was provided by Cochrane
      Collaboration. RESULTS: Six randomized controlled trials (RCTs) covering 1951
      patients with MM were included in the analysis. The clodronate subgroup showed
      superior progression-free survival compared to the other groups. The pooled
      hazard ratio (HR) was 0.57 [95% confidence interval (CI) 0.33-0.99, P = 0.04].
      Regarding overall survival (OS), only zoledronic acid showed a clear advantage
      (HR = 0.51, 95% CI 0.33-0.77, P = 0.002) All BPs were effective at reducing
      skeletal-related events (SREs). The pooled risk ratios for the outcome of SREs
      were 0.72 (95% CI: 0.62-0.84, P < 0.0001) for the clodronate subgroup, 0.66 (95%
      CI: 0.48-0.91, P = 0.007) for the pamidronate subgroup, and 0.65 (95% CI: 0.46
      0.91, P = 0.01) for the zoledronic acid subgroup. Several adverse events (AEs)
      were mentioned in the included RCTs; however, the pooled results showed no
      statistically significant differences between the BP groups and the control.
      CONCLUSIONS: The present meta-analysis demonstrated that zoledronic acid may
      improve the OS of patients with MM. All BPs markedly decreased SREs and were
      tolerated well.

PMID- 26221213
TI  - Association between maternal smoking during pregnancy and recurrent wheezing in
      infancy: evidence from a meta-analysis.
AB  - BACKGROUND: Quantification of the association between the maternal smoking during
      pregnancy and recurrent wheezing in infancy is still conflicting. Thus, we
      performed a comprehensive meta-analysis to test the hypothesis that maternal
      smoking during pregnancy may increase the risk of recurrent wheezing in infancy.
      METHODS: Pertinent studies were identified by a search in PubMed and Web of
      Knowledge up to October 2014. Random-effect model (REM) or fixed effects model
      (FEM) was used to combine study-specific results. Publication bias was estimated
      using Egger's regression asymmetry test. RESULTS: Seven articles (3 cohort study
      and 4 cross-sectional studies) involving 8579 recurrent wheezing infant cases
      about maternal smoking during pregnancy and recurrent wheezing risk were used in
      this meta-analysis. The combined relative risks (RRs) of recurrent wheezing
      infants associated with maternal smoking during pregnancy was 1.491 (95% CIs =
      1.329-1.672) overall. Significant associations were found both in Europe [RRs =
      1.471, 95% CIs = 1.287-1.681] and other populations [RRs = 1.720, 95% CIs = 1.119
      2.644] and cross-sectional studies [RRs = 1.474, 95% CIs = 1.306-1.663]. No
      publication bias was found. CONCLUSIONS: Our analysis indicated that maternal
      smoking during pregnancy could increase the risk of recurrent wheezing in
      infancy.

PMID- 26221214
TI  - Hepatoid adenocarcinoma of the stomach is a special and easily misdiagnosed or
      missed diagnosed subtype of gastric cancer with poor prognosis but curative for
      patients of pN0/1: the experience of a single center.
AB  - AIM: To document the clinicopathological characteristics and analyze the possible
      reasons for misdiagnosis or missed diagnosis of hepatoid adenocarcinoma of the
      stomach (HAS), using data from a single center. METHODS: We retrospectively
      analyzed 19 patients initially diagnosed as HAS and 7 patients initially
      diagnosed as common gastric cancer with high levels of serum alpha-fetoprotein
      (AFP). All had undergone surgical treatment, except 3 patients only had biopsies
      at our hospital. Immunohistochemistry for AFP and Hepatocyte antigen was
      performed. Final diagnosis for these 26 patients were made after HE and
      immunohistochemistry slides reviewed by 2 experienced pathologists. Prognostic
      factors were determined by univariate analysis. RESULTS: Nineteen cases were
      confirmed to be HAS. A total of 4 out of 19 cases initially diagnosed as HAS and
      4 out of 7 cases initially diagnosed as common gastric adenocarcinoma were
      misdiagnosed/missed diagnosed, thus, the misdiagnosis/missed diagnosis rate was
      30.8% (8/26). The incidence of HAS among gastric cancer in our center was 0.19%
      (19/9915). Sixteen (84.2%) patients showed T stages greater than T2, 12 (70.6%)
      patients had positive lymph nodes in 17 available patients and 3 (15.8%) of the
      patients with tumors presented liver metastasis at the time of diagnosis.
      Histologically, cytoplasmic staining types included 10 cases of eosinophilic, 1
      case of clear, 5 cases of clear mixed with eosinophilic and 3 cases of
      basophilic. Fourteen (73.7%) patients expressed AFP, whereas only 6 (31.6%) were
      hepatocyte-positive. Univariate analysis showed that N stage (HR 2.429, P=0.007)
      and tumor AFP expression (HR 0.428, P=0.036) were significantly associated with
      disease-free survival. The median overall survival time was 12.0 months, and the
      median disease-free survival time was 7.0 months. Four (80%) of 5 N0 patients and
      2 (50%) of 4 N1 patients survived without progression, but no N2-3 patients
      survived. CONCLUSION: HAS remains easily being misdiagnosed/missed diagnosed
      based on a pathological examination, probably because the condition is rare and
      has various cytoplasmic types. Although the survival rate for HAS is poor, a
      curative effect may be achieved for N0 or N1 cases.

PMID- 26221215
TI  - The up-regulation of miR-300 in gastric cancer and its effects on cells
      malignancy.
AB  - OBJECTIVE: In this study, we investigated the role of miR-300 in regulating cell
      proliferation and invasion of gastric cancer cells. METHODS: MicroRNA and protein
      expression patterns were compared between gastric cancer tissue and normal tissue
      and between two different prognostic groups. The up-regulation of miR-300 was
      confirmed by real-time reverse transcription polymerase chain reaction and its
      expression was analyzed in AGS gastric cancer cells. RESULTS: We observed that
      miR-300 expression was frequently and dramatically up-regulated in human gastric
      cancer tissues and cell lines compared with the matched adjacent normal tissues
      and cells. We further showed that transient and stable over-expression of miR-300
      could promote cell proliferation and cell cycle progression. Moreover, p53, a key
      inhibitor of cell cycle, was verified as a direct target of miR-300, suggesting
      that miR-300 might promote gastric cancer cell proliferation and invasion by
      increasing p53 expression. CONCLUSION: Our findings indicated that miR-300 up
      regulation might exert some sort of antagonistic function by targeting p53 in
      gastric cancer cell proliferation during gastric tumorigenesis.

PMID- 26221216
TI  - Efficacies of surgical treatments based on Harris hip score in elderly patients
      with femoral neck fracture.
AB  - AIM: To compare the efficacies of four surgical treatments, i.e., total hip
      arthroplasty (THA), internal fixation (IF), hemiarthroplasty (HA), and artificial
      femoral head replacement (artificial FHR), by performing a network meta-analysis
      based on Harris hip score (HHS) in elderly patients with femoral neck fracture.
      METHODS: In strict accordance with specific inclusion and exclusion criteria,
      randomized controlled trails (RCTs) were screened and selected from a larger
      group of studies that were retrieved through a comprehensive search of scientific
      literature databases, further complimented by manual search. The resultant high
      quality data from final selected studies were analyzed using Stata 12.0 software.
      RESULTS: A total of 3680 studies were initially retrieved from database search,
      and 15 RCTs were eventually incorporated into this meta-analysis, containing 1781
      elderly patients who had undergone various surgical treatments for femoral neck
      fracture (THA group = 604; HA group = 604; IF group = 495; artificial FHR group =
      78). Our major result revealed a statistically significant difference in HHS of
      femoral neck fracture when HA and IF groups were compared with THA. No
      differences were detected in the HHS of femoral neck fracture undergoing
      artificial FHR and THA. The surface under the cumulative ranking curves (SUCRA)
      value of HHS, in elderly patients with femoral neck fracture after surgery,
      revealed that IF has the highest value. CONCLUSIONS: The current network meta
      analysis results suggest that IF is the superlative surgical procedure for
      femoral neck fracture patients, and IF significantly improves the HHS in femoral
      neck fracture patients.

PMID- 26221217
TI  - ALDH2 attenuates Dox-induced cardiotoxicity by inhibiting cardiac apoptosis and
      oxidative stress.
AB  - The anthracycline chemotherapy drug doxorubicin (DOX) is cardiotoxic. This study
      aimed to explore the effect of acetaldehyde dehydrogenase 2 (ALDH2), a
      detoxifying protein, on DOX-induced cardiotoxicity and unveil the underlying
      mechanisms. BALB/c mice were randomly divided in four groups: control group (no
      treatment), DOX group (DOX administration for myocardial damage induction), DOX +
      Daidzin group (DOX administration + Daidzin, an ALDH2 antagonist) and DOX + Alda
      1 group (DOX administration + Alda-1, an ALDH2 agonist). Then, survival,
      haemodynamic parameters, expression of pro- and anti-apoptosis markers, reactive
      oxygen species (ROS) and 4-Hydroxynonenal (4-HNE) levels, expression and
      localization of NADPH oxidase 2 (NOX2) and its cytoplasmic subunit p47(PHOX), and
      ALDH2 expression and activity were assessed. Mortality rates of 0, 35, 5, and 70%
      were obtained in the control, DOX, DOX + Alda-1, and DOX + Daidzin groups,
      respectively, at the ninth weekend. Compared with control animals, DOX treatment
      resulted in significantly reduced left ventricular systolic pressure (LVSP) and
      +/- dp/dt, and overtly increased left ventricular end-diastolic pressure (LVEDP);
      increased Bax expression and caspase-3/7 activity, and reduced Bcl-2 expression
      in the myocardium; increased ROS (about 2 fold) and 4-HNE adduct (3 fold) levels
      in the myocardium; increased NOX2 protein expression and membrane translocation
      of P47(PHOX). These effects were aggravated in the DOX + Daidzin group, DOX +
      Alda-1 treated animals showed partial or complete alleviation. Finally, Daidzin
      further reduced the DOX-repressed ALDH2 activity, which was partially rescued by
      Alda-1. These results indicated that ALDH2 attenuates DOX-induced cardiotoxicity
      by inhibiting oxidative stress, NOX2 expression and activity, and reducing
      myocardial apoptosis. 

PMID- 26221218
TI  - Amelioration of meconium-induced acute lung injury by parecoxib in a rabbit
      model.
AB  - Cyclooxygenase-2 (COX-2) plays important roles in various inflammatory conditions
      and is significantly increased in meconium-induced lung injury. We investigated
      the effects of parecoxib on meconium-induced acute lung injury (ALI) in rabbits.
      Twenty-four rabbits were randomized into sham, control, and parecoxib groups.
      Rabbits in the control and parecoxib groups underwent tracheal instillation of
      meconium, followed by intravenous injection of saline or parecoxib and 4 h of
      ventilation. The airway pressure, dynamic compliance, and ratio of partial
      pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO2/FiO2
      ratio) were recorded at baseline (T0) and 4 h after instillation (T1-T4). The
      lung tissue wet-to-dry weight ratio; neutrophil percentage; and total protein,
      tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-8,
      prostaglandin E2, and malondialdehyde levels in bronchoalveolar lavage fluid
      (BALF) were evaluated. The myeloperoxidase activity, COX-2 expression, and degree
      of histopathologic injury in lung tissue were also analyzed. The airway pressure,
      compliance, and PaO2/FiO2 ratio were significantly improved by parecoxib after
      meconium instillation. The lung wet-to-dry weight ratio, total protein level, and
      neutrophil percentage in BALF were lowest in the parecoxib group. The TNF-alpha,
      IL-1beta, IL-8, prostaglandin E2, and malondialdehyde levels in the BALF were
      lowest in the parecoxib group. The COX-2 expression and myeloperoxidase activity
      in lung tissue were significantly reduced by parecoxib. The degree of lung injury
      was also reduced. In conclusions: Parecoxib effectively ameliorates respiratory
      function and attenuates meconium-induced ALI. These effects are correlated with
      prostaglandin E2 and COX-2 inhibition. 

PMID- 26221219
TI  - Effects and safety of magnesium sulfate on propofol-induced injection pain, a
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Propofol is the most widely used drug in the induction of general
      anesthesia, however its disadvantages of injection pain has always been a problem
      for clinical anesthetists. Many strategies have been proposed and magnesium
      sulfate is one of them. This is the first meta-analysis studies evaluating
      effects of magnesium sulfate pretreatment for preventing propofol-induced
      injection pain. METHODS: We searched MEDLINE, EMBASE, Google scholar and the
      Cochrane Database of Systematic Review databases for randomized controlled trials
      (RCTs) that evaluated the prophylactic effect of magnesium sulfate on propofol
      injection pain. Meta-analyses were performed using RevMan 5.3 software. RESULTS:
      Five RCTs involving 545 participants were included. Magnesium sulfate allows more
      patients experiencing no pain or mild pain during propofol injection ([RR] 2.70,
      95% [CI] 1.10-6.64, P=0.03, 2.12,95% CI 1.46-3.08, P < 0.0001, respectively). And
      the number of patients with severe pain (RR 0.12, 95% CI 0.06-0.25, P < 0.00001)
      on injecting propofol were significantly decreased. However, no statistical
      significance was found between magnesium sulfate group and placebo group in
      moderate pain (RR 0.22, 95% CI 0.05-0.97, P=0.05). CONCLUSION: Our meta-analysis
      suggested that pretreatment with magnesium sulfate intravenously before injecting
      propofol allow more patients to experiencing no pain during propofol injection
      and can reduce the intensity of injection pain effectively without causing any
      adverse effect.

PMID- 26221220
TI  - Evaluation of cardiac function by pacing at different right ventricular sites in
      patients with third-degree atrioventricular block using Doppler ultrasound.
AB  - OBJECTIVE: This study utilized Doppler ultrasonography cardiograms in patients
      with third-degree atrioventricular (III-AV) block to compare right ventricular
      apex (RVA) pacing and right ventricular outflow tract (RVOT) pacing with respect
      to their effects on synchronization of contraction between the two ventricles, as
      well as on timing of specific left-ventricular electrical and mechanical events
      and their impact on left ventricular function. METHODS: Thirty-eight patients
      with (III-AV) block were implanted with dual-chamber pacemakers, in 20 cases,
      implantation occurring in the RVOT (RVOT group), while in 18 cases implantation
      occurred in the RVA (RVA group). Patients underwent Doppler echocardiography and
      electrocardiography (ECG) one month pre- and one month post-surgery, as well as
      12 months post-surgical implantation of the pacemaker. RESULTS: Prior to
      pacemaker implantation, no significant differences were found between the two
      groups with respect to the following parameters: left ventricular end-diastolic
      diameter (LVEDD), left ventricular end systolic diameter (LVESD), left
      ventricular ejection fraction (LVEF), E/A value (ratio of early [E] to late [A]
      ventricular filling velocities), inter-ventricular mechanical delay (IVMD)and
      septal-to-posterior wall motion delay (SPWMD). One month after implantation, no
      significant differences were found between the two groups for LVEDD, LVESD, LVEF,
      and E/A. However, compared with the RVOT group, the RVA group exhibited prolonged
      IVMD and SPWMD. Twelve months after pacemaker implantation, there was no
      significant difference for E/A between the two groups; however, compared with the
      ROVT group, the RVA group exhibited prolonged LVEDD, LVESD, IVMD, and SPWMD and
      significantly lower LVEF. CONCLUSION: Relative to RVA pacing, RVOT pacing
      mitigated impairment of systolic function and systolic dys-synchronization.

PMID- 26221221
TI  - Protoporphyrin IX catalyzed hydrogen peroxide to generate singlet oxygen.
AB  - AIM: To study the role of protoporphyrin IX (pPIX) in mitochondrial metabolism of
      hydrogen peroxide (H2O2). METHODS: O2 (-) specific fluorescent markers DMA (9,10
      dimerthylanthracence) and SOSG (Singlet Oxygen Sensor Green reagent) were used
      for measurement of singlet oxygen ((1)O2). Catalyzing conversion of H2O2 into
      (1)O2 by pPIX was monitored in vitro under varied H2O2 content, temperature, and
      PH value in the reaction. Ex vivo mitochondrial model was used to analyze effects
      of ferrochelatase (FECH) and high energy X-rays on this catalytic reaction.
      RESULTS: In complete dark, measurable (1)O2 was generated when 1.5 mM of H2O2 was
      incubated with 24 MUM of pPIX H2O2 at 37 degrees C for 3 hours. Mitochondrial
      yield of H2O2 was 0.11+/-0.03 nmole/mg/min. Mitochondrial FECH significantly
      improve the catalytic ability of pPIX converting H2O2 into (1)O2. At presence of
      high-energy X-ray, incubation of 14.4 MUM of pPIX with 0.54 MUM of H2O2 also
      generated (1)O2, during which the fluorescence density of 1.05 MUM of DMA
      decreased by 41.5% (P < 0.05). This conversion was not observed when pPIX was
      replaced with structurally similar hematoporphyrin. CONCLUSION: pPIX can catalyze
      conversion of H2O2 into (1)O2.

PMID- 26221222
TI  - Associations between CTLA-4 +49 A/G (rs231775) polymorphism and cancer risk: a
      meta-analysis based on 52 case-control studies.
AB  - OBJECTIVES: To date, a number of epidemiological studies have explored the
      association between CTLA-4 +49 A/G polymorphism and cancer risk with elusive
      results. To address this gap, we carried out a comprehensive meta-analysis.
      DESIGN AND METHODS: Two reviewers independently searched the PubMed, EMBASE, CBM
      (Chinese BioMedical Disc) and China National Knowledge Infrastructure (CNKI)
      Databases for relevant studies up to December 20, 2014. Odds ratios (ORs) with
      95% confidence intervals (CIs) for CTLA-4 +49 A/G polymorphism and cancer risk
      were used to evaluate the strength of association. RESULTS: A total of 52 case
      control studies were ultimately recruited. Our results showed the statistical
      evidence of an association between the CTLA-4 +49 A/G polymorphism and decreased
      risk of overall cancer in all the comparison models. In stratified analyses by
      cancer type, ethnicity and the origin of cancer, significant decreases in cancer
      risk were observed in breast cancer, lung cancer, other cancers epithelial tumor
      and Asians. In addition, in a stratified analysis by the system of cancer,
      significant decreases in cancer risk were found for reproductive and breast
      cancer, respiratory system cancer, and malignant bone tumor in all the genetic
      models, and other system cancer in two genetic models: GG+AG vs. AA and GG vs.
      AA. CONCLUSIONS: This meta-analysis suggests that the CTLA-4 +49 A/G polymorphism
      may be a protective factor for cancer.

PMID- 26221223
TI  - Reduced beta 2 glycoprotein I improve diabetic nephropathy via inhibiting TGF
      beta1-p38 MAPK pathway.
AB  - PURPOSE: Beta 2 glycoprotein I (beta2GPI) has been shown the positive effect on
      diabetic atherosclerosis and retinal neovascularization. beta2GPI can be reduced
      by thioredoxin-1, resulting in the reduced state of beta2GPI. The possible
      protective effects of beta2GPI and reduced beta2GPI on diabetic nephropathy (DN)
      are not fully elucidated. The purpose of this study was to test a hypothesis that
      beta2GPI and reduced beta2GPI would improve DN in streptozotocin (STZ) induced
      diabetic mice and high-glucose (HG) exposed rat mesangial cell (RMC). METHODS:
      The STZ-induced Balb/c mice and HG exposed RMCs were administrated with beta2-GPI
      and reduced beta2-GPI at different time and concentrations gradient respectively.
      The changes of glomerular structure and expression of collagen IV, TGF-beta1, p38
      MAPK and phospho-p38 MAPK in renal cortical and mesangial cells were observed by
      immunohistochemical techniques, quantitative real-time PCR and western blot with
      or without the treatment of beta2-GPI and reduced beta2-GPI. RESULTS: beta2GPI
      and reduced beta2GPI improved early clinical and pathological changes of DN in
      STZ-diabetic mice. Treatment with beta2GPI and reduced beta2GPI in the STZ
      diabetic mice and HG exposed RMCs resulted in decrease expression levels of TGF
      beta1 and collagen IV, with concomitant decrease in phospho-p38 MAPK expression.
      CONCLUSIONS: beta2GPI and reduced beta2GPI improved renal structural damage and
      kidney function. The renoprotective and antifibrosis effects of beta2GPI and
      reduced beta2GPI on DN were closely associated with suppressing the activation of
      the TGF-beta1-p38 MAPK pathway.

PMID- 26221224
TI  - The effect of PDIA3 gene knockout on the mucosal immune function in IBS rats.
AB  - OBJECTIVE: To observe the changes of intestinal inflammation on PDIA3 gene
      knockout IBS rats and its effect on immune function. METHODS: 36 SD rats were
      randomly divided into four groups: the control group (n = 8); IBS- empty virus
      group (IBS-GFP, which); IBS-PDIA3 knockout group (n = 12); IBS- the control group
      (n = 12). After modeling, colon and ileocecal tissue pathology in each group were
      observed separately. Changes of immune and inflammatory markers were measured. At
      the same time, ultrastructural changes in each group were observed by electron
      microscopy. RESULTS: Compared with the IBS control group, inflammation was
      reduced significantly in IBS-PDIA3 knockout group. IgE, IL-4 and IL-9 and the
      level of intestinal trypsin type were decreased significantly. Furthermore, mast
      cell degranulation and PAR 2 receptor reduced significantly. CONCLUSION: PDIA3
      may play an important role in the development of IBS by mediating through immune
      responses of mucosal abnormalities. However, the mechanism needs to be confirmed
      in further study.

PMID- 26221225
TI  - A pooled analysis of alcohol intake and colorectal cancer.
AB  - OBJECT: In order to provide an updated quantification of the association between
      alcohol intake and colorectal cancer, we conducted a meta-analysis of published
      observational studies. METHOD: Two cohort and 22 case-control studies presenting
      results for at least three categories of alcohol intake were identified from a
      PubMed search of articles published before July 2014. Data were extracted
      independently by two reviewers. Random effects meta-analyses, subgroup analyses,
      and meta regression were performed for modeling the dose-response relation.
      RESULT: The pooled relative risk (RR) for any alcohol intake compared with
      non/occasional drinking was 1.13 [95% confidence interval (CI), 1.09-1.17]. The
      RRs were 1.07 (95% CI, 1.02-1.13), 1.23 (95% CI, 1.15-1.32) and 1.37 (95% CI,
      1.26-1.49) for light (<=12.5 g/day), moderate (12.6 to 49.9 g/day) and heavy
      drinking (>=50 g/day), respectively. The risks were consistent in the subgroup
      analyses of sex and tumor site. CONCLUSION: This meta-analysis provides strong
      evidence for an association between alcohol intake and colorectal cancer risk.

PMID- 26221226
TI  - Lung morphometry changes in prevention of airway remodeling by protocatechuic
      aldehyde in asthmatic mice.
AB  - Airway remodeling can lead to irreversible airflow obstruction and persistent
      airway hyper-responsiveness, which is the pathological basis of refractory
      asthma. To investigate the preventive effect of protocatechuic aldehyde on airway
      remodeling in asthmatic mice by lung morphometry methods. BALB/c mice were used
      to establish model of airway remodeling by ovalbumin (OVA) inhalation.
      Bronchoalveolar lavage fluid (BALF) were collected for eosinophils (EOS) count
      and detection of interleukin 4 (IL-4), interleukin-13 (IL-13) and interferon (IFN
      gamma) content. The left lung pathological sections were performed HE, AB-PAS and
      Masson staining. The epithelial lamina thickness of the left main bronchus (Re),
      the smooth muscle layer thickness (Rm), the number of goblet cells and goblet
      cell area percentage (%Ac) and gas side of the road and vascular collagen
      deposition (%Aco, %Avc) situation were measured. Protocatechuic aldehyde gavage
      made the reduction of BALF EOS count. IL-4 and IL-13 levels also decreased, while
      the IFN-gamma level increased. The left main bronchus Re, Rm, goblet cell count,
      Ac% and Aco% and Avc% reduced. Protocatechuic aldehyde can significantly control
      airway inflammation and prevent airway remodeling. 

PMID- 26221227
TI  - Effect of culture complex of BMSCs and sodium hydroxide- and GRGDSPC-treated PET
      on the reconstruction of injured anterior cruciate ligament in a rabbit model.
AB  - Ligament reconstruction is an effective therapy for anterior cruciate ligament
      (ACL) rupture. Polyethylene terephthalate (PET) artificial ligaments have
      recently gained popularity in clinical ACL reconstruction for its advantage in
      the improvement of keen function. However, the application of PET in clinical
      treatment is limited by its poor bioactivity and biocompatibility. Recently, bone
      marrow-derived mesenchymal stem cells (BMSCs) have been widely studied in
      regenerative medical therapy due to their multi-lineage differentiation. Previous
      study also indicated that BMSCs may promote the healing of tendon-bone interface
      of injured ligament. We speculate that BMSCs may enhance the curative effect of
      PET artificial ligament on the tendon-bone-healing in ligament reconstruction. In
      this study, the PET materials were first modified with sodium hydroxide
      hydrolysis and GRGDSPC peptide which was able to improve its bioactivity and
      biocompatibility. Then, the effects of modified PET materials on the adhesion,
      proliferation and differentiation of BMSCs were examined. The in vitro co-culture
      of BMSCs and modified PET showed the modified PET promoted the adhesion,
      proliferation and differentiation of BMSCs. Further, the effect of culture
      complex of BMSCs and modified PET artificial ligament co-culture system on the
      injured ligament reconstruction was investigated in vivo. Results showed not only
      better growth and differentiation of BMSCs but also satisfactory healing of the
      injured ligament was observed after implantation of this culture complex into the
      injured ligament of rabbits. Our study provides a brand-new solution for ACL
      reconstruction. 

PMID- 26221228
TI  - The tumor protection effect of high-frequency administration of whole tumor cell
      vaccine and enhanced efficacy by the protein component from Agrocybe aegerita.
AB  - Whole tumor cell vaccines have been widely studied and elicits limited immune
      responses because of the poor immunogenicity. In the present study, we discovered
      that high-frequency administration of irradiated whole tumor cell vaccine
      triggered rejection of tumor cells (90% or 100% of the mice that were vaccinated
      with irradiated H22 cells or S180 respectively were protected), and provided
      cross-protection and long-term anti-tumor immunity in BALB/c mouse models. The
      antitumor activity required CD4+, CD8+ T cells and macrophage that was proved in
      the nude mice and cell depletion mouse models. The adoptive transfer experiment
      suggested that repeated whole tumor cell vaccination successfully stimulated the
      anti-tumor response by activation of the immune cells. A high immunization
      frequency within a short period of time and the presence of glycosylated
      molecules and nucleic acids on the surface of intact tumor cells were crucial for
      the successful prevention of tumor growth by whole tumor cell vaccines. Moreover,
      Yt, the protein component from fungus Agrocybe aegerita, increased whole tumor
      cell vaccine-mediated tumor rejection and cross-protection effect. These data
      indicated that the frequency of administration of whole tumor cell vaccines was
      of critical importance for the efficacy, which needed to be integrated into
      vaccine strategies for producing potential vaccines. 

PMID- 26221229
TI  - Schisandrin B inhibits the proliferation of human lung adenocarcinoma A549 cells
      by inducing cycle arrest and apoptosis.
AB  - Lung cancer is the leading cause of cancer death in the world. Schizandrin B (Sch
      B) is one of the main dibenzocyclooctadiene lignans present in the fruit of
      Schisandra chinensis (Schisandraceae). Sch B has multiple functions against
      cancer. The aim of this study was to determine the effect of Sch B on the
      proliferation, cell cycling, apoptosis and invasion of lung adenocarcinoma A549
      cells by MTT, flow cytometry, wound healing and transwell invasion assays.
      Treatment with Sch B inhibited the proliferation of A549 cells in a dose
      dependent manner. Sch B induced cell cycle arrest at G0/G1 phase by down
      regulating the expression of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK6,
      but up-regulating p53 and p21 expression in A549 cells. Furthermore, Sch B
      triggered A549 cell apoptosis by increasing Bax, cleaved caspase-3, 9, Cyto C,
      but decreasing Bcl-2 and PCNA expression. In addition, Sch B inhibited the
      invasion and migration of A549 cells by down-regulating the expressions of HIF-1,
      VEGF, MMP-9 and MMP-2. Therefore, Sch B has potent anti-tumor activity and may be
      a promising traditional Chinese medicine for human lung carcinoma. 

PMID- 26221230
TI  - Platelet mitochondrial dysfunction of DM rats and DM patients.
AB  - It is known that cardiovascular complications plays important roles in the
      development of diabetes mellitus (DM) and platelet dysfunction is one of the key
      reasons which led to microangiopathy. This study was designed to investigate the
      mitochondria function changes of platelet in DM rats and DM patients. The results
      showed that the platelets viability, platelet adenosine triphosphate (ATP)
      content and platelet mitochondrial ATP content of DM rats were lower than that of
      normal rats; when incubated in vitro for 24 h, platelet number and mitochondrial
      membrane potential (MMP) of DM rats were lower than that of normal rats, reactive
      oxygen species (ROS) was higher than that of normal rats. For DM patients, their
      platelet number and ROS were higher and MMP was lower than those of normal
      people; when incubated in vitro for 24 h, platelet viability of DM patients was
      lower than that of normal people. Platelet ultra-microstructures of DM rats and
      DM patients were abnormal. These results suggested that platelet mitochondrial
      function of both DM rats and DM patients was impaired when compared to normal
      rats and normal people, respectively. Platelets may be applied as a biomarker to
      observe the mitochondrial changes during DM. 

PMID- 26221231
TI  - The 5-hydroxytryptamine transporter is functional in human coronary artery smooth
      muscle cells proliferation and is regulated by Interleukin-1 beta.
AB  - Abnormal human coronary artery smooth muscle cells (hCASMCs) proliferation and
      migration are key factors in coronary artery restenosis after percutaneous
      coronary intervention. Platelets release 5-hydroxytryptamine (5-HT), which is a
      strong mitogen for pulmonary artery smooth muscle cells proliferation and
      migration. Here, we investigated the effects of 5-HT and role of 5-HT transporter
      (5-HTT) on hCASMCs proliferation and migration. The 5-HT (10(-6)-10(-5) mol/l)
      significantly increased hCASMCs proliferation and migration, and these effects
      were inhibited by fluoxetine (10(-5) mol/l) and citalopram (10(-6) mol/l), two 5
      HTT blocker. Overexpression in hCASMCs enhanced 5-HT induced cells proliferation
      and migration. The 5-HTT and interleukin-1 beta (IL-1beta) expression were
      increased in rat balloon injury carotid arteries. Treatment with IL-1beta (10
      ng/ml, 3d) upregulates 5-HTT expression in hCASMCs and increased 5-HT induced
      currents in Human Embryonic Kidney 293-5-HTT cells. 

PMID- 26221232
TI  - MiR-300 regulate the malignancy of breast cancer by targeting p53.
AB  - OBJECTIVE: In this study, we investigated the role of miR-300 in regulating cell
      proliferation and invasion of breast cancer (BC) cells. METHODS: MicroRNA and
      protein expression patterns were compared between breast cancer tissue and normal
      tissue and between two different prognostic groups. The up-regulation of miR-300
      was confirmed by real-time reverse transcription polymerase chain reaction and
      its expression was analyzed in MCF-7 breast cancer cells. RESULTS: We observed
      that miR-300 expression was frequently and dramatically up-regulated in human
      breast cancer tissues and cell lines compared with the matched adjacent normal
      tissues and cells. We further showed that transient and stable over-expression of
      miR-300 could promote cell proliferation and cell cycle progression. Moreover,
      p53, a key inhibitor of cell cycle, was verified as a direct target of miR-300,
      suggesting that miR-300 might promote breast cancer cell proliferation and
      invasion by regulating p53 expression. CONCLUSION: Our findings indicated that
      miR-300 up-regulation might exert some sort of antagonistic function by targeting
      p53 in breast cancer cell proliferation during breast tumorigenesis.

PMID- 26221233
TI  - Integrin beta4 in EMT: an implication of renal diseases.
AB  - Renal fibrosis is a main cause of chronic renal failure. Epithelial-to
      mesenchymal transition (EMT) markers play a role in renal fibrosis. Transforming
      growth factor-beta1 (TGF-beta1) has been shown to initiate and complete the whole
      EMT process. It is now well accepted that loss of E-cadherin, EMT marker alpha
      SMA, and connective tissue growth factor (CTGF) expression are key events in the
      EMT process. We found that by stimulating human renal proximal tubular epithelial
      (HK-2) cells with TGF-beta1, the expression of E-cadherin was down regulated and
      the expression of alpha-SMA and CTGF were up regulated in a dose dependent
      manner. In our present study we also found that integrin beta4 and peroxisome
      proliferators-activated receptor-gamma (PPAR-gamma) play roles in EMT process,
      with TGF-beta1 stimulation increasing integrin beta4 expression in HK2 cells.
      Integrin beta4 and PPARgamma were detected in tubulointerstitial tissues,
      immunohistochemistry analysis showed enhanced expression of integrin beta4 in
      early stage, with over-expression at later stage. In contrast, the expression of
      PPARgamma showed little increased in early stage, but was dramatically decreased
      at later stage. This is consistent with TGF-beta1 inducing EMT. Our immune
      precipitation studies show that integrin beta4 disassociation with PPARgamma is
      present in E-cadherin signaling. It suggests that PPARgamma has a role in EMT
      inhibition. 

PMID- 26221234
TI  - Promising response of anaplastic lymphoma kinase-positive large B-cell lymphoma
      to crizotinib salvage treatment: case report and review of literature.
AB  - Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (ALK +
      DLBCL) is a rare and poorly characterized subtype of lymphoma. Reports suggest
      that this type of tumor responds poorly to standard regimens for non-Hodgkin's
      lymphoma, with rituximab playing no therapeutic role due to the absence of CD20
      expression. In view of the expression of ALK in this disease, it is plausible
      that the ALK inhibitor crizotinib may be an effective treatment. We report a case
      of a 21-year-old male ALK + DLBCL patient. He initially received five cycles of
      CHOP-21 (vincristine, pirarubicin, cyclophosphamide and prednisone) and achieved
      a partial remission (PR) but soon deteriorated. He was subsequently treated with
      five courses of the salvage chemotherapy regimen ICE (ifosfamide, carboplatin and
      etoposide) and achieved PR again. He refused to accept an autologous stem-cell
      transplantation, after which the disease progressed rapidly. We administered two
      courses of an alternative salvage chemotherapy regimen containing GEMOX and
      dexamethasone with the addition of the ALK inhibitor crizotinib. His symptoms
      alleviated for a short time but soon worsened and the patient died of massive
      progressive disease. 

PMID- 26221235
TI  - Qian Five Rhinoceros Gindeng (QFRG) protects against development of immune
      thrombocytopenia via miR-181a inhibition of TLR-4 expression.
AB  - AIMS: Traditional Chinese medicine (TCM) has been considered to be effective
      auxiliary strategy for the treatment of hemocytopenia including immune
      thrombocytopenia. However, the molecular mechanism is still not understood.
      METHODS: In present study, Qian Five Rhinoceros Gindeng (QFRG) mainly containing
      buffalo horn, rehmannia root, radix rubia, trogopterus dung and radix salviae
      miltiorrhizae administrated to thrombocytopenia mice induced by injection of
      MWReg30. MicroRNAs (miRNAs), Toll Like Receptors (TLRs) and cytokines were
      assayed in monocytes separated from mice peripheral blood. The relationship
      between miRNAs and TLRs was investigated in Mouse leukaemic monocyte macrophage
      cell line RAW264.7. RESULTS: The mice with administration of QFRG had a
      significant increase in platelet count, and miR-181a of monocytes was markedly up
      regulated in QFRG treated group. QFRG also decreased the levels of TLR4, IL-6 and
      TNF-alpha. In addition, miR-181a inhibitor reversed the effects of QFRG on
      platelet count, TLR4 and cytokines. Overexpression of miR-181a in
      lipopolysaccharide-induced showed a decrease of TLR4, IL-6 and TNF-alpha level.
      CONCLUSIONS: QFRG protects against development of immune thrombocytopenia via miR
      181a inhibition of TLR-4 expression.

PMID- 26221236
TI  - Nitric oxide regulates blastocyst hatching in mice.
AB  - OBJECTIVE: This study is to determine the regulatory role of nitric oxide in
      mouse blastocyst hatching. METHODS: Kunming female mice were superovulated and
      then mated with mature male mice. On day 2.5 of their pregnancy, the pregnant
      mice were killed and morulae were flushed from their uterine horns with culture
      media. Morulae were cultured in media with different concentrations of N-nitro-L
      arginine methyl ester (L-NAME), sodium nitroprusside (SNP), 8-Br-3'-5'-cyclic
      guanosine monophosphate (8-Br-cGMP) or the combination of L-NAME with SNP or 8-Br
      cGMP for 48 h. The hatched blastocysts were examined on day 5 and the expressions
      of epithelial nitric oxide synthase (eNOS) and active cysteinyl aspartate
      specific proteinase 3 (caspase 3) were observed under confocal laser scanning
      microscope. RESULTS: L-NAME significantly reduced the expression of eNOS in
      blastocyst cells. With the increase of the concentrations of L-NAME, SNP or 8-Br
      cGMP, blastocyst hatching rate was significantly lowered. In addition, 5 mM L
      NAME, 2 MUM SNP and 2 MUM 8-Br-cGMP completely inhibited blastocyst hatching. Low
      concentrations of SNP or 8-Br-cGMP in culture media containing 5 mM L-NAME
      significantly reversed the inhibition of blastocyst hatching and promoted
      hatching development. Moreover, 5 mM L-NAME and 2 MUM 8-Br-cGMP had no
      significant influence on the expression of active caspase 3 in blastocyst cells.
      SNP (> 500 nM) significantly increased the expression of active caspase 3 in
      blastocyst cells. CONCLUSIONS: NO/cGMP pathway plays an important role in mouse
      blastocyst hatching. Excessive or depleted NO can interrupt blastocyst hatching.
      Excessive NO leads to apoptosis of blastocyst cells.

PMID- 26221237
TI  - Cancer-associated fibroblasts from NSCLC promote the radioresistance in lung
      cancer cell lines.
AB  - The purpose of present study was to investigate the radiosensitivity of lung
      cancer cells affected by human lung cancer-associated fibroblasts (CAFs) in
      transwell and direct co-culture in vitro. Human lung CAFs was obtained from fresh
      human lung adenocarcinoma tissue specimens by primary culture with tissue
      explants method, and was identified by immunofluorescence staining. The
      radiosensitivity of A549 and H1299 lung cancer cells in mono-culture, transwell
      and direct co-culture with human lung CAFs were investigated by clonogenic
      survival assay, respectively. Human lung CAFs were obtained successfully, and had
      specific immuno-staining with alpha-SMA, Vimentin, and FAP, and no cytokeratin-18
      expression. The plating efficiency (PE) of A549 cells without receiving
      irradiation were 0.206+/-0.031, 0.210+/-0.007 (>0.05) and 0.352+/-0.023 (<0.05)
      in mono-culture, transwell and direct co-culture, respectively. The PE of H1299
      cells were 0.200+/-0.039, 0.259+/-0.024 (>0.05) and 0.323+/-0.025 (<0.05) in mono
      culture, transwell and direct co-culture, respectively. The clonogenic survival
      assay showed that the protection enhancement ratio of human lung CAFs in
      transwell and direct co-culture were 1.11 and 1.29 for A549 cells, and 1.15 and
      1.25 for H1299 cells, respectively. The results suggested that human lung CAFs
      promote the radioresistance of lung cancer cells significantly. Its
      radioprotective effect may attribute to CAFs stimulating lung cancer cell
      proliferation. 

PMID- 26221238
TI  - RELMalpha can cause contraction of rat aortic smooth muscle cells.
AB  - OBJECTIVE: This study aims to observe the contraction role of RELMalpha in rat
      aortic smooth muscle cells and explore its mechanism. METHODS: Rat aortas smooth
      muscle cells were cultivated using tissue explants method. They were divided into
      5 groups. A: Control group; B: 1*10(-7) mol/L ANGII group; C: 1*10(-8) mol/L
      RELMalpha group; D: 2*10(-8) mol/L RELMalpha group; E: 4*10(-8) mol/L RELMalpha
      group. The thoracic aortic tension signal of rats was recorded by Powerlab
      system. The expression levels of CaM and MLCK were detected by western blotting
      and RT-PCR methods. RESULTS: Tension changes of rat thoracic aorta vascular ring
      in group C, D and E (72+/-2.98%, 76.65+/-2.73%, 85.07+/-3.06% respectively) were
      higher than that of group A and B (6.35+/-0.75%, 61.47+/-4.47%) with dose
      dependent (P<0.01). The expression levels of CaM and MLCK in group C were higher
      than that of group A and B while were lower than that of group D and E (P<0.05).
      The expression levels of CaM and MLCK in group E were the highest among the
      groups (P<0.05). CONCLUSIONS: RELMalpha can cause contraction of rat aortic
      smooth muscle cells, its mechanism may be via Ca(2+)-CaM-MLCK pathway.

PMID- 26221239
TI  - Early quantitative CT analysis of oleic acid induced acute respiratory distress
      syndrome in a canine model.
AB  - BACKGROUND: Although quantitative computed tomography (CT) has been used to
      analyze the lungs of patients with confirmed diagnoses of acute respiratory
      distress syndrome (ARDS), there are few reports to show the diagnosis during the
      early stage of ARDS. Using a canine model and quantitative CT, we aimed to
      develop an oleic acid (OA) induced ARDS regarding the early stage of ARDS that
      could improve in the early diagnosis of ARDS. METHODS: Fourteen healthy beagle
      dogs underwent CT. Their lung tissue was manually partitioned into four
      compartments, i.e., non-aerated, poorly aerated, normally aerated, and hyper
      aerated lung compartments. The mean CT attenuation value Hounsfield unit (HU),
      tissue mass (g), residual volume (ml), and percentage of lung area were
      automatically determined for each lung compartment and compared between groups by
      receiver operating characteristic curve (ROC) analyses using area under curve
      (AUC). The optimized cut-off point for each parameter was determined by Youden's
      index. RESULTS: Regarding lung compartments during the expiratory phase, the
      percentage of non-aerated lung area in the ARDS group was higher vs. controls at
      all time points (T1 to T6). CT attenuation values for the ARDS group increased
      with time during both respiratory phases compared with controls. During both
      respiratory phases, tissue mass within the ARDS group significantly increased
      compared with controls at T3-T6. CONCLUSIONS: Quantitative CT analysis can detect
      ARDS at an early stage with high sensitivity and specificity, providing a minimum
      of assistance in the early diagnosis of ARDS.

PMID- 26221240
TI  - Distinct role of Tim-3 in systemic lupus erythematosus and clear cell renal cell
      carcinoma.
AB  - Tim-3 is considered as one of the T-cell immunoglobulin mucin (TIM) gene family
      members, which contributes to the activating or silencing genes, but the
      mechanism of Tim-3 function in mediating SLE or tumor metastasis has not been
      well explored. Here, we reported Tim-3 was high expressed in the peripheral blood
      mononuclear cells (PBMCs) of patients with SLE, detected by RT-PCR,
      significantly, GATA-3 mRNA expression also increased in patients with SLE,
      compared with the healthy control groups. The bioinformatics used to detect the
      TCGA database indicated the abnormal expression of Tim-3 was involved in several
      different cancer types. Further, the higher expression of Tim-3 in kidney renal
      clear cell carcinoma TCGA database indicated it was a marker for worse 5-year
      survival. The high expression of Tim-3 in different ccRCC cell lines was detected
      in both RNA level and protein level. Further, two kinds of relative Tim-3 siRNAs
      in ccRCC cell lines inhibit cell migration and invasion in vitro, However, the
      inhibition could be partially rescued by the additional GATA3 knockdown. Further,
      the down regulation in the RNA and protein levels of GATA3, and the negative
      correlation between Tim-3 and GATA3 implied that suppression of downstream GATA3
      was an important mechanism by which Tim-3 triggered metastasis in ccRCC cell
      lines. Together, our experiments reveal the role for Tim-3 in facilitating SLE or
      invasive potential of ccRCC cells by either activating GATA3 or inhibiting GATA3,
      suggesting that Tim-3 might be a potential therapeutic target for treating SLE or
      clear cell renal cell carcinoma. 

PMID- 26221241
TI  - Efficacy of radical and conservative surgery for hepatic cystic echinococcosis: a
      meta-analysis.
AB  - OBJECTIVE: To systematically evaluate the efficacy and safety of radical surgery
      (RS) and conservative surgery (CS) in the treatment of hepatic cystic
      echinococcosis (HCE). METHODS: We searched PubMed, Embase, MEDLINE, SCI, CNKI,
      CBM, and WanFang databases, and the Cochrane Library (2013, Issue 3) for
      references published before December 2013. Both randomized and non-randomized
      controlled trials of radical and conservative surgery for HCE were collected.
      After the literature was screened in accordance with inclusion and exclusion
      criteria, data were extracted and the quality of methodologies of selected
      references was determined independently by two evaluators. A meta-analysis was
      performed on eligible studies with RevMan 5.1 statistical software. RESULTS: Five
      non-randomized controlled trials (1267 patients) were included in this study.
      Patients in the RS group had fewer postoperative complications compared with the
      CS group [OR = 0.42, 95% CI (0.32, 0.56), P < 0.00001], whereas there was no
      significant difference in rates of postoperative bile leakage between the two
      groups [OR = 0.22, 95% CI (0.05, 1.12), P = 0.07]. Postoperative follow-up of
      patients revealed a significantly lower HCE recurrence rate in the RS versus CS
      group [OR = 0.17, 95% CI (0.08, 0.38), P < 0.0001]. Additionally, no statistical
      differences in the number of days of hospitalization [MD = -2.47, 95% CI (-6.42,
      1.49), P = 0.22] and perioperative mortality [OR = 0.87, 95% CI (0.27, 2.79), P =
      0.82] were identified between groups. CONCLUSION: RS, especially total
      pericystectomy, has obvious advantages over CS: fewer complications, lower
      postoperative recurrence, and a lower incidence of biliary fistula and infection,
      making RS the preferred surgical method. This conclusion requires further
      validation with high-quality RCTs with large sample sizes. Surgical approach
      should be based upon comprehensive assessment of individual circumstances in HCE
      patients.

PMID- 26221242
TI  - Autophagic regulation of cell growth by altered expression of Beclin 1 in triple
      negative breast cancer.
AB  - Beclin 1 is a promoter gene for autophagy as well as a key factor for regulating
      tumor cell growth and death. Allelic deletion of Beclin 1 has been observed in
      certain triple-negative breat cancer (TNBC) cells, and it might be associated
      with increased proliferation and invasion in TNBC cells. In this study we
      investigated the relationship between Beclin 1 expression and prognosis for TNBC
      patients, as well as the influence on cell growth by Beclin 1 overexpression in
      different cultural conditions. Beclin 1 expression in TNBC tissues was measured
      by immunohistochemical staining and correlated with clinicopathologic parameters
      for TNBC patients. The plasmid of pDS-RED-C1-Beclin 1 was transfected to BT-549
      and MDA-MB-231 cells and autophagy, proliferation, apoptosis, cell cycle and
      Epithelial-mesenchymal transition (EMT) process were measured. Results indicated
      that high level of Beclin 1 expression was correlated with more lymph nodes and
      distant metastasis but unrelated to survival rates in 5 years for TNBC patients.
      In vitro, overexpression of Beclin 1 improved cellular autophagy in both BT-549
      and MDA-MB-231 cells, inhibited cell proliferation at normal cultural condition
      and increased cell survival in starvation, hypoxia or with doxorubicin
      stimulation. Besides, Beclin 1 overexpression decreased cell apoptosis, induced
      cells to be in G0/G1 phase and promoted EMT process through Wnt/beta-catenin
      pathway in starvation. Thus, Beclin 1 overexpression plays a double role in BT
      549 and MDA-MB-231 cell growth by elevating the capability of autophagy. These
      findings might be useful for searching a proper method for clinical therapy of
      TNBC from the aspect of autophagy in future. 

PMID- 26221243
TI  - Diagnostic performance of interleukin-6 and interleukin-8 for bacterial
      meningitis: a meta-analysis.
AB  - This study aimed to summarize the overall diagnostic performance of interleukin-6
      and interleukin-8 in cerebrospinal fluid for bacterial meningitis through meta
      analysis due to inconclusive results reported. Literature search was performed in
      PubMed and Embase to identify eligible studies. Data were retrieved and
      sensitivity, specificity, positive likelihood ratio/negative likelihood ratio
      (PLR/NLR), and diagnostic odds ratio (DOR) were pooled. Summary receiver
      operating characteristic curve and the area under the curve (AUC) were calculated
      to evaluate their overall test performances. Thirteen studies were included for
      present meta-analysis. The summary estimates for interleukin-6 in diagnosing
      bacterial meningitis were: sensitivity, 0.91 (95% CI 0.81-0.96); specificity,
      0.93 (95% CI 0.84-0.97); PLR, 12.38 (95% CI 5.42-28.29); NLR, 0.10 (95% CI 0.04
      0.21); DOR, 129.76 (95% CI 41.48-405.88); and AUC 0.97 (95% CI 0.95-0.98). The
      corresponding summary performance estimates for interleukin-8 were as follows:
      sensitivity, 0.95 (95% CI 0.71-0.99); specificity, 0.89 (95% CI 0.77-0.95); PLR,
      8.50 (95% CI, 3.83-18.86); NLR, 0.06 (95% CI 0.01-0.40); DOR, 154.25 (95% CI
      14.56-1634.33); and AUC 0.95 (95% CI 0.93-0.97). Measurements of interleukin-6
      and interleukin-8 play a valuable role in diagnosing bacterial meningitis.
      Nevertheless, their results should be interpreted in parallel with the results of
      routine tests and clinical symptoms. 

PMID- 26221244
TI  - Effects of artemether on the proliferation, apoptosis, and differentiation of
      keratinocytes: potential application for psoriasis treatment.
AB  - Artemether exhibits diverse pharmacological effects and has multiple
      applications. This study aimed to investigate its antiproliferative and
      apoptogenic effects on HaCaT cells and keratinocyte differentiation-inducing
      activity in vivo. WST-8 analysis demonstrated that Artemether can inhibit the
      proliferation of cultured HaCaT cells in a time- and dose-dependent manner.
      Annexin V/PI dual staining and JC-1 staining further revealed that Artemether can
      dose-dependently augment HaCaT apoptosis. To investigate the keratinocyte
      differentiation-inducing activity of Artemether, it was prepared as topical
      creams at concentrations of 1%, 3%, and 5%. During the 4 weeks of topical
      treatment, no evidence of irritation was observed in the mouse tail test.
      Artemether cream dose-dependently increased the degree of orthokeratosis and the
      relative epidermal thickness of mouse tail skin, indicative of the keratinocyte
      differentiation-inducing activity. Taking the in vitro and in vivo findings
      together, the present study suggests that Artemether may be a promising
      antipsoriatic agent worthy of further investigation. 

PMID- 26221245
TI  - Loss of regulatory T cell function on anti-inflammation is correlated with
      increased risk of acute kidney injury development in patients with primary
      glomerulonephritis.
AB  - Inflammation is believed to play a major role in the pathophysiology of acute
      kidney injury (AKI). The injury induces the generation of inflammatory mediators
      like cytokines and chemokines by tubular and endothelial cells which contribute
      to the recruiting of leukocytes into the kidneys. Early AKI risk evaluation is
      limited to demographic characteristics and past clinical histories, and no
      specific treatment is available. To better identify patients at risk of
      developing AKI, and devise more targeted treatment and prevention regimen, we
      tracked 158 primary glomerulonephritis patients for their occurrence of AKI, and
      analyzed the characteristics of their adaptive immune system. We found that in
      patients that later developed AKI, peripheral blood T cell composition is shifted
      toward IFN-g-producing Th1-like cells. While the composition of CD4(+)CD25(+) T
      cells were similar between patients that later developed AKI and patients without
      AKI development, in patients that later developed AKI, their CD4(+)CD25(+) T
      cells secreted less regulatory cytokine IL-10, and was unable to suppress
      proinflammatory cytokine production by CD4(+) T cells, while in patients without
      AKI development, CD4(+)CD25(+) T cells were able to suppress CD4(+) T cell
      mediated IFN-g and IL-17 expression under stimulation, partially through IL-10
      secretion. Collectively, we identified a defect in CD4(+)CD25(+) T cell
      regulatory function in patients at risk of developing AKI. 

PMID- 26221246
TI  - Shear wave elastography (SWE) is reliable method for testicular spermatogenesis
      evaluation after torsion.
AB  - This study aims to investigate effect of torsion on testicular stiffness
      alteration in affected and concomitant testis using improved ultrasound method of
      shear wave elastography (SWE). We compared the morphology of the testicular
      spermatogenesis assessed with Johansen's scale on histology specimens with a mean
      stiffness measured by SWE. A total of 18 New Zealand white male rabbits were
      divided into two groups (group A and group B), animals from group A were
      subjected to operation of right testicle torsion while left testicle remained
      intact. In group B both testicles were normal and right testicle was subjected to
      sham operation. The protocol of measurement for mean stiffness value was
      calculated from three elastographic images obtained from each testicle.
      Significant difference in mean stiffness value and Johnsen' scaling was observed
      in both groups (A and B), as well as for normal and torted testicle in group A.
      The mean stiffness positively correlated with histologic grade on both sided
      testicles in group B, and left sided testicles in group A (P=0.045, r=0.43; group
      B; P=0.001, r=0.98), while histologic grade negatively correlated with mean
      stiffness in the group A, torted testicle (torsion P=0.012, r=-0.76). In this
      study testicular torsion, with consequently higher mean stiffness value
      determined by SWE, has qualitatively and quantitatively decreased
      spermatogenesis. Gradual morphology change in testicle unaffected by torsion has
      not been previously reported. This study confirmed that quantitative change in
      testicular tissue stiffness as well as change in testicular spermatogenesis can
      be reliably evaluated with SWE. 

PMID- 26221247
TI  - Liver involvement of Langerhans' cell histiocytosis in children.
AB  - OBJECTIVE: Liver involvement is relatively frequent in children with Langerhans
      cell histiocytosis (LCH). Its features remain poorly defined. METHODS: A
      retrospective study was carried out on 14 hepatic LCH children in our hospital.
      The Clinicopathological and radiological features of this disease was discussed.
      RESULTS: The rate of liver involvement in children LCH patients is 51.9%.
      Majority of the patients were disseminated cases. Hepatomegaly was clinically
      confirmed in 11 cases (78.6%). Liver function dysfunction was seen in nine
      (64.3%) children. The association of multi-modal imaging significantly yielded
      more diagnostic information. There are some imaging characteristics of this
      disease, CT and MRI could help to assess the staging, extent of the hepatic
      lesions. We found that liver involvement had a significant impact on survival.
      Patients treated with systemic chemotherapy earlier from time of diagnosis had a
      relatively better outcome. CONCLUSIONS: The rate of liver involvement in children
      LCH patients maybe much higher than that of expected. We suggest that clinical
      and biological liver evaluation and abdominal imaging must be performed regularly
      onwards to screen every LCH children patient from the time of the initial
      diagnosis. Patient should be treated with systemic chemotherapy earlier.

PMID- 26221248
TI  - Aqueous extract of Caesalpinia sappan decelerates allograft rejection by inducing
      imbalance between CD4(+) CD25(+) T cells and Th17 cells.
AB  - OBJECTIVE: Aqueous extract of Caesalpinia sappan (CSE) has immunosuppressive
      activities, but the mechanism remains unknown. This study was to investigate the
      effect of CSE on the balance between CD4(+) CD25(+) T cells and Th17 cells.
      METHODS: Allografted Balb/c recipients were intraperitoneally treated with CSE
      for 14 continuous days, and the graft survival was observed. The spleen cells and
      peripheral blood of the recipient mice were harvested for phenotyping by flow
      cytometry, detection of gene expression by real-time PCR and cytokine detection
      by ELISA. RESULTS: CSE prolonged skin allograft survival, increased the
      percentage and number of CD4(+) CD25(+) T cells, the expression of Foxp3 and
      STAT5 in spleen cells, the serum levels of IL-10 and TGF-beta1, whereas reduced
      the percentage and number of Th17 cells and serum IL-17 level in Balb/c
      recipients. CONCLUSION: CSE expanded CD4(+) CD25(+) T cells and decreased Th17
      cells in vivo thereby improving skin allograft survival in mice, indicating that
      CSE affects the balance between CD4(+) CD25(+) T cells and Th17 cells in the
      graft to induce rejection.

PMID- 26221249
TI  - Association of OPN overexpression with tumor stage, differentiation, metastasis
      and tumor progression in human laryngeal squamous cell carcinoma.
AB  - BACKGROUND: Osteopontin (OPN) is overexpressed in many human tumors and involved
      in promotion of cancer cells by regulating various facets of tumor progression
      such as cell proliferation, invasion and metastasis. To understand roles of OPN
      in tumor progression of laryngeal squamous cell carcinoma (LSCC) or develop
      molecular marker for prognosis and treatment of LSCC, we thus explore biological
      function of OPN and correlation with p53 in LSCC. METHODS: The expression of OPN
      and p53 in tumor tissues of LSCC was determined immunohistochemically in both
      LSCC and adjacent normal tissues. Lentivirus vector with RNAi small hairpin gene
      sequence of OPN (named LV-shOPN) was transfected into Hep-2 cells. OPN expression
      was detected by Western blotting assay and the viability and invasive ability of
      Hep-2 cells were examined by MTS and transwell assay. RESULTS: We found that OPN
      and p53 protein expressions were significantly higher in LSCC tumor tissues than
      adjacent normal tissues (76.2% vs. 23.8% for OPN and 63.8% vs. 15.2% for p53, all
      P < 0.001). OPN expression was also significantly correlated with p53 expression,
      tumor stage, grade and the presence of lymph node. The constructed LV-shOPN
      effectively inhibited the OPN expression, viability and invasive ability of Hep-2
      cells (all P < 0.050). CONCLUSION: Taken together, OPN is overexpressed in LSCC.
      OPN expression is correlated with p53 expression, tumor progression and lymph
      node metastasis. Additionally, RNAi silencing of OPN expression can significantly
      inhibit tumor viability and invasion ability of Hep-2 cells. Thus, OPN may be
      considered as a marker and potential gene targeting therapy in LSCC.

PMID- 26221250
TI  - Icariin stimulates the proliferation of rat bone mesenchymal stem cells via ERK
      and p38 MAPK signaling.
AB  - Bone mesenchymal stem cells (BMSCs) are able to differentiate into multi types of
      lineages, so they have been widely applied in the stem cell transplantation. The
      BMSCs are usually needed to be expanded before transplantation due to their
      limited content in bone marrow. It has recently been reported that Icariin (ICA),
      a major constituent of flavonoids from the Chinese medical herb Epimedium
      brevicornum Maxim, promotes the proliferation of various types of differentiated
      cells. However, whether ICA can enhance BMSCs proliferation and the possible
      underlying mechanisms are still unknown. After being isolated and purified from
      rat bone marrow, cultured BMSCs are stimulated with different concentrations of
      ICA. The cytotoxicity of ICA is evaluated by the Cell Counting Kit-8 (CCK-8)
      assay method and the ICA optimal concentration for BMSCs proliferation is
      determined at 320 MUg/L. Our work reveals that ICA induces an obvious
      phosphorylation of ERK and p38 kinases in BMSCs, no matter serum exists or not.
      Inhibition of ERK or p38 MAPK signaling by their specific inhibitors PD98059 or
      SP600125, respectively, not only prevents the activation of these kinases, but
      also attenuates cell proliferation induced by ICA. Furthermore, the downstream
      transcription factors of MAPK pathway, Elk1, Stat3, c-Myc and Fos, are also
      monitored by RT-PCR, and our results show that among them, Elk1 and c-Myc are
      significantly upregulated after ICA treatment. Taken together, our results
      demonstrate that ICA promotes the proliferation of rat BMSCs through activating
      ERK and p38 MAPK signaling which further leads to upregulation of their
      downstream transcription factors Elk1 and c-Myc. Our work provides a novel
      effective way to expand the content of BMSCs in vitro, which casts light on
      clinical applications of stem cell transplantation in the future. 

PMID- 26221251
TI  - Screening feature genes of osteosarcoma with DNA microarray: a bioinformatic
      analysis.
AB  - To screen differentially expressed genes (DEGs) of Osteosarcoma (OS) by using the
      microarray expression profiles of tissues of normal person and patients with OS
      for early diagnosis and effective treatment of OS. We downloaded the gene
      expression profile of GES16088 from Gene Expression Omnibus database, including
      twenty samples from fourteen patients diagnosed with osteosarcoma and six normal
      samples as control groups. We identified the DEGs by Affy package in R language.
      Bioinformatic methods were used for further analysis of the screened DEGs.
      Firstly, cluster analysis was performed on the selected DEGs for comparison of
      the expression degree. After protein-protein interaction (PPI) network of
      differentially expressed genes was constructed by STRING, we analyzed gene
      functions with DAVID and WebGestalt. Compared with the control, we screened three
      distinctly up-regulated genes. These DEGs had close relationship with
      transmission signaling pathway, organ and system development. The up-regulated
      gene COL was the most representative genes among the DEGs. The screened DEGs have
      a great significance on studying mechanism of osteosarcoma. It might distinguish
      normal and pathological tissues of OS and thus become target genes for
      monitoring, diagnosis and treatment of the OS. It has the potential to use in
      clinic. 

PMID- 26221252
TI  - Treatment of complex proximal humeral fracture: plate and tension band fixation
      versus conservative therapy.
AB  - BACKGROUND: There is no consensus on the optimal treatment for patients with
      complex proximal humeral fractures. A meta-analysis was performed to evaluate
      clinical effectiveness of plate and tension band fixation compared with
      conservative therapy. METHODS: We systematically searched electronic databases
      (Pubmed, Medline, Embase, Cochrane library and Google Scholar) to identify
      comparative studies and randomized controlled trials in which plate and tension
      band fixation was compared with conservative treatment of the complex proximal
      humeral fractures from 1995 to 2013. The quality of the studies was assessed and
      effective data were pooled for meta-analysis. RESULTS: A total of 222 patients
      from three RCTs and three comparative studies were included in this meta-analysis
      (113 fractures treated with plate and tension band and 109 with conservative
      treatment). The primary and secondary outcomes (Constant Score, nonunion,
      avascular necrosis and osteoarthritis) were compared and there was no significant
      difference among these different treatments of this injury. CONCLUSIONS: Compared
      with conservative treatment, internal fixation including plate and tension band
      did not find better shoulder function, higher rate avascular necrosis of humeral
      head, lower rate nonunion, and higher rate osteoarthritis. In further, high
      quality and large randomized trials should be recommended to make a choice
      between these treatment modalities.

PMID- 26221253
TI  - Intrathecal SRT1720, a SIRT1 agonist, exerts anti-hyperalgesic and anti
      inflammatory effects on chronic constriction injury-induced neuropathic pain in
      rats.
AB  - Neuropathic pain is caused by lesion or inflammation of the nervous system and
      characterized by the symptoms of allodynia, hyperalgesia and spontaneous pain.
      SIRT1 (Sir2) is a NAD-dependent deacetylase and is reported to regulate a wide
      variety of cellular processes including inflammation, aging and lifespan
      extension. Nevertheless, the role of SIRT1 in neuropathic pain is not fully
      understood. The present study was intended to detect the effect of intrathecal
      SRT1720, a SIRT1 agonist, using quantitative real-time PCR and western blot
      analysis over time in rats following chronic constriction injury (CCI) or sham
      surgery. In addition, the effect of intrathecal injection of SRT1720 on thermal
      hyperalgesia and mechanical allodynia was evaluated in CCI rats. It was found
      that daily intrathecal injection of SRT1720 before and 1, 3, 5, 7 days after CCI
      surgery produced a transient inhibitory effect on thermal hyperalgesia and
      mechanical allodynia in CCI rats. In addition, an intrathecal injection of STR1
      siRNA before SRT1720 administration reversed the anti-nociceptive effect of
      SRT1720. Furthermore, intrathecal injection of SRT1720 significantly down
      regulated the expression of mammalian target of rapamycin (mROT), NF-kappaB and
      inflammatory cytokines, such as IL-6, TNF-alpha and iNOS mRNA. These data
      indicate that intrathecal SRT1720 may be an alternative strategy for the
      treatment of neuropathic pain. Our findings suggest that intrathecal SRT1720, a
      SIRT1 agonist, exerts antihyperalgesic and antiinflammatory effects on CCI
      induced neuropathic pain in rats. 

PMID- 26221254
TI  - Lead exposure causes thyroid abnormalities in diabetic rats.
AB  - Lead is a widely-spread environmental pollutant and a commonly-used industrial
      chemical that can cause multisystemic adverse health effects. However, the
      effects of lead exposure on diabetic animals have not been reported so far. The
      aim of this study is to evaluate the effects of lead exposure on thyroid, renal
      and oxidative stress markers in diabetic Wistar rats. Diabetes was induced with
      an intraperitoneal (i.p.) injection of streptozocin (STZ). Six weeks later, rats
      were exposed i.p. to either distilled water (control group) or 25, 50 and 100
      mg/kg of lead acetate (treatment groups). We found a positive relationship
      between the administered doses of lead acetate and its measured levels in blood
      samples (P < 0.01). Treatment of diabetic animals with lead acetate resulted in
      significant weight loss (P < 0.001). It also caused an increase in thyroid
      stimulating hormone levels (P < 0.05) and reductions in thyroxine (P < 0.05) and
      triiodothyronine levels (P < 0.01), a clinical picture consistent with
      hypothyroidism. Lead acetate exposure increased urea levels (P < 0.05) and caused
      a significant decrease in creatinine (P < 0.05). Besides, while the
      concentrations of malondialdehyde were not affected, glutathione stores were
      depleted (P < 0.01); in response to lead exposure. In conclusion, exposure of
      diabetic rats to lead acetate resulted in weight loss, clinical hypothyroidism,
      renal damage and oxidative stress. 

PMID- 26221255
TI  - Honokiol induces cell cycle arrest and apoptosis via p53 activation in H4 human
      neuroglioma cells.
AB  - OBJECTIVE: To investigate the signal pathway of honokiol-induced apoptosis in H4
      human neuroglioma cells and to evaluate whether p53 signaling and cell cycle
      arrest were involved in honokiol-treated H4 human neuroglioma cells. METHODS: The
      cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by
      annexin V-PI double-labeling staining and hoechst 33342 staining. The protein
      expression of cell cycle regulators and tumor suppressors were analyzed by
      western blotting. RESULTS: Treatment of H4 human neuroglioma cells with honokiol
      induced cell death in a dose-and time-dependent manner by using CCK8 assay.
      Consistent with the CCK8 assay, the flow cytometry results showed that the
      proportion of the apoptosis cells increased after honokiol when compared with
      untreated group. Moreover, H4 human neuroglioma cells exposed to honokiol,
      resulted in an accumulation of cells in S and G2/M phase. Apoptotic bodies were
      clearly observed in human neuroglioma cells when treated with honokiol and then
      stained with Hoechst 33342. The expression of Cyclin B1, CDC2 and cdc25C were
      downregulated, however, the expression of p-CDC2 and p-cdc25c was significantly
      upregulated when the neuroglioma cells were exposed to honokiol. Moreover, p53,
      p21 and Bax/Bcl-2 were significantly upregulated by honokiol treatment.
      CONCLUSIONS: These results confirmed that honokiol could induce apoptosis in
      human neuroglioma cells, the underlying molecular mechanisms, at least partially,
      through activation p53 signaling and induction of cell cycle arrest.

PMID- 26221256
TI  - Current evidence on the relationship between two common polymorphisms in NPAS2
      gene and cancer risk.
AB  - The relationship between neuronal PAS domain protein 2 (NPAS2) gene polymorphisms
      and cancer risk has been widely investigated. However, the results are
      conflicting. We performed this meta-analysis to derive a more precise estimation
      on the relationship. We searched Pubmed, and Web of Knowledge databases until
      Dec, 2014 to identify eligible studies. Case-control studies containing available
      genotype frequencies of the NPAS2 polymorphisms were chosen. The odds ratios
      (ORs) with 95% confidence interval (CI) were used to assess the strength of
      association. Eight independent case-control studies with 3,857 cancer patients
      and 4,525 cancer-free controls were selected for this meta-analysis. Two NPAS2
      gene polymorphisms were identified (rs2305160 and rs17024926). The results showed
      statistically significant associations of rs2305160 with cancer risk (AA+GA vs.
      GG: OR = 0.84, 95% CI = 0.72-0.98, P = 0.02; AG vs. GG: OR = 0.81, 95% CI = 0.68
      0.96, P = 0.02). Stratified analysis by cancer type indicated that rs2305160 may
      decrease the risk of breast cancer (A vs. G: OR = 0.87, 95% CI = 0.76-0.96, P =
      0.006; AA+GA vs. GG: OR = 0.77, 95% CI = 0.67-0.88, P<0.001; AG vs. GG: OR =
      0.74, 95% CI = 0.64-0.86, P<0.001), whereas negative results were obtained for
      prostate cancer. For rs17024926 polymorphism, there was no significant
      association in any genetic model. This meta-analysis suggests that NPAS2
      rs2305160 polymorphism may reduce cancer susceptibility, especially in breast
      cancer. 

PMID- 26221257
TI  - Outflow facility efficacy of five drugs in enucleated porcine eyes by a method of
      constant-pressure perfusion.
AB  - This study aimed to characterize a technique that assesses the outflow facility
      (C) efficacy of five kinds of IOP-lowering drugs commonly used clinically in
      enucleated porcine Eyes. Eyes were perfused at 15 mmHg with GPBS first to
      establish the baseline outflow facility (C0). Then the anterior chamber contents
      were exchanged for GPBS with corresponding concentration eye drops (4.9*10(3) nM
      Brimonidine, 41.1 nM Latanoprost, 3.4*10(3) nM Levobunolol, 3.0*10(3) nM
      Brinzolamide, 8.3*10(3) nM Pilocarpine) in five groups (n = 6 each), while 6 eyes
      received GPBS alone as control. The mean stable facility obtained after drug
      administration (C1) was continuously recorded. The changes between C0 and C1
      (DeltaC = C1-C0) were analyzed. Finally, for drugs among the five experiment
      groups with statistical significance, the concentration was reduced 3 times,
      otherwise the drugs' concentration was increased to 10 times to confirm its
      effectiveness further using the same methods (n = 6 each). We found that the
      average baseline outflow facility was 0.24+/-0.01 MUl.min(-1).mmHg(-1). C
      increased significantly in Brimonidine and Latanoprost groups, even the
      concentration of Brimonidine and Latanoprost was decreased 3 times (P < 0.05).
      However, there was no significantly increase in Levobunolol, Brinzolamide,
      Pilocarpine and control group (P > 0.05), but when drugs' concentration was
      increased to 10 times, the C value of Pilocarpine decreased significantly (P =
      0.04). No significant washout effects in porcine eyes were observed. To conclude,
      outflow facility efficacy of five drugs in enucleated porcine eyes may provide a
      reference for clinical medicine. A constant-pressure perfusion technique should
      be useful to evaluate effect of pharmacologic agents or surgical manipulations on
      aqueous humor dynamics. 

PMID- 26221258
TI  - Pathological changes of cochlear in deaf mice at different time after mouse
      cytomegalovirus infection.
AB  - OBJECTIVE: This study aims to observe the pathological changes of inner ear in
      deaf mice at different time after mouse cytomegalovirus infection. METHODS: A
      total of 60 BALB/C mice were divided into 2 groups randomly: model group (A) and
      control group (B). In model group, 10 MUl of MCMV was injected into the brain of
      each mouse while 10 MUl of physiological saline was injected in control group. 10
      cochlear samples were taken from 5 mice selected from each group randomly after
      infection for 1, 3, 5, 7, 14 and 21 days respectively. They were detected with
      PCR and HE staining methods. Auditory brain stem response was determined. The
      apoptosis of spiral ganglion (SGN) cells was detected by apoptosis assay kit. The
      levels of Bcl-2 and Bax were detected by RT-PCR and western blotting methods.
      RESULTS: In group A, PCR results were negative after infection for 1 day, they
      were positive after infection for 3 days to 21 days. In group B, PCR results were
      negative in the experimental period. Compared with group B, ABR I wave latency
      and threshold increased while ABR I wave decreased in group A. There were no
      obvious hyperemia and inflammatory cells infiltration in group B, In group A,
      hemorrhage of scala tympani and scala vestibule appeared and reached highest peak
      after infection for 3 days accompanied by inflammatory cell infiltration; the
      vestibular membrane thickened after infection for 5 days; cell gap of SGN cells
      widened, arranged more sparsely with cell edema after infection for 7 days
      accompanied by infiltration of plasma cells; fibroblast proliferation and
      fibrosis appeared after infection for 14 days. CONCLUSIONS: MCMV infection
      occurred in cochlear after MCMV infection for 3 days and could sustain, the
      continues pathological changes of inner will bring difficulties to the treatment
      of CMV deafness, further studies on the specific mechanism of SGN changes caused
      by CMV infection will provide an important target for the treatment of CMV
      deafness.

PMID- 26221259
TI  - Effect of statins treatment for patients with aneurysmal subarachnoid hemorrhage:
      a systematic review and meta-analysis of observational studies and randomized
      controlled trials.
AB  - Vasospasm is one of the most common complications after aneurysmal subarachnoid
      hemorrhage.Statins have been proven to be effective to reduce the incidence of
      vasospasm both in experimental subarachnoid hemorrhage and several clinical
      trials before. This meta-analysis aimed to investigate the efficacy of statins
      for patients with aneurysmal subarachnoid hemorrhage. We made strict search
      strategies to select the randomized controlled trial and observational studies
      published up to December 20(th) 2014. Outcomes of interest were cerebral
      vasospasm, delayed cerebral ischemia and poor outcome. Data analyses of RCTs and
      observational studies were made separately. Finally six randomized clinical trial
      and eight observational studies were included in this meta-analysis. There were
      in total 1031 patients in six RCTs with 504 patients received statins and 527
      patients in placebo group. 561 patients with statins compared with 1579 patients
      in no statin-use group were finally included in 8 observational studies. Outcomes
      included in this meta-analysis (cerebral vasospasm, DIC and poor outcome) all
      indicated no statistical significance between two groups both in RCTs and
      observational studies. No benefits of statins-use for patients with aneurysmal
      subarachnoid hemorrhage were observed in both RCTs and observational studies,
      which was quite different from the results of several previous meta-analysis. 

PMID- 26221260
TI  - Evaluating the microRNA-target gene regulatory network in renal cell carcinomas,
      identification for potential biomarkers and critical pathways.
AB  - Variant microRNA (miRNA) expression is a character of many cancer types. The
      combined analysis of miRNA and messenger RNA (mRNA) expression profiles is
      crucial to identifying links between deregulated miRNAs and oncogenic pathways.
      The aim of this study was to screen several novel genes associated with renal
      cell carcinoma (RCC), and analyze the gene functions and signal pathways which
      were critical to RCCs with DNA microarray. The gene expression profile of GSE6344
      was downloaded from Gene Expression Omnibus database, including 10 RCC samples
      and 10 healthy controls. Compared with the control samples, differentially
      expressed genes (DEGs) of RCC was identified. The selected DEGs were further
      analyzed using bioinformatics methods. Gene ontology (GO) enrichment analysis was
      performed using Gene Set Analysis Toolkit and protein-protein interaction (PPI)
      network was constructed with prePPI. Then, pathway enrichment analysis to PPI
      network was performed using WebGestalt software. We found that a total of 521
      DEGs were down-regulated and 473 DEGs were up-regulated in RCC samples compared
      to healthy controls. A total of 15 remarkable enhanced functions and 17
      suppressed functions were identified. PPI nodes of high degrees, such as RHCG,
      RALYL, SLC4A1, UMOD and CA9, were obtained. The DEGs were classified and
      significantly enriched in cytokine and cytokine receptor pathway. The hub genes
      we find from RCC samples are not only biomarkers, but also may provide the
      groundwork for a combination therapy approach for RCCs. 

PMID- 26221261
TI  - Depletion of MEIS2 inhibits osteogenic differentiation potential of human dental
      stem cells.
AB  - Dental mesenchymal stem cells (MSCs) are a reliable and promising cell source for
      the regeneration of tooth,bone and other tissues . However, the molecular
      mechanisms underlying their differentiation are still largely unknown, which
      restricts their further wide application. Here, we investigate regulatory
      function of homeobox gene MEIS2 in the osteogenic differentiation potential of
      MSCs using stem cells from apical papilla (SCAPs) and dental pulp stem cells
      (DPSCs) by loss-of-function experiments. Our findings demonstrated that knockdown
      of MEIS2 in SCAPs and DPSCs decreased alkaline phosphatase (ALP) activity and
      mineralization, and inhibited the mRNA expression of ALP, bone sialoprotein
      (BSP), and osteocalcin (OCN). Besides, depletion of MEIS2 resulted in reduced
      expression of the key osteogenesis-related transcription factor, osterix (OSX)
      but not in the expression of runt-related transcription factor 2 (RUNX2).
      Furthermore, MEIS2 expression significantly increased during osteogenic induction
      and was strongly upregulated by BMP4 stimulation. Taken together, these results
      indicated that MEIS2 played an essential role in maintaining osteogenic
      differentiation potential of dental tissue- derived MSCs. These findings will
      provide new insights into the mechanisms underlying directed differentiation of
      MSCs, and identify a potential target gene in dental tissues derived MSCs for
      promoting the tissue regeneration. 

PMID- 26221262
TI  - Fuzhisan, a chinese herbal medicine, suppresses beta-secretase gene transcription
      via upregulation of SIRT1 expression in N2a-APP695 cells.
AB  - The accumulation of beta-amyloid (Abeta) peptide plaques is the major pathogenic
      event in Alzheimer's disease (AD). Because beta-site amyloid precursor protein
      cleaving enzyme 1 (BACE1) cleaves APP at the first amino acid of the Abeta domain
      and is the rate-limiting enzyme for Abeta peptide generation, the level of this
      aspartic protease is a focus of AD research. Fuzhisan (FZS), a Chinese herbal
      complex prescription that has been used for the treatment of AD for over 20
      years, is known to enhance metabolic activity and cognitive ability in aged rats
      and AD patients. To confirm whether FZS's therapeutic effect related to BACE1
      pathway, we investigated the intracellular molecules expression change after FZS
      treatment in N2a-APP695 cell line. In this study, we demonstrated that BACE1
      transcription and translation were reduced, and SIRT1 expression was elevated in
      the N2a-APP695 cells treated with FZS. The therapeutic efficacy of FZS in AD may
      be derived from the downregulation of BACE1 expression. 

PMID- 26221263
TI  - Circulating microRNAs in esophageal squamous cell carcinoma: association with
      locoregional staging and survival.
AB  - Locoregional staging and prognostic information play a critical role in
      esophageal squamous cell carcinoma (ESCC) treatment strategies. Although microRNA
      (miRNA) is a promising marker for cancer detection, the relationship between
      circulating plasma miRNAs and ESCC remains unclear. Our study aims to investigate
      the association between circulating plasma miRNAs and tumor diagnosis or
      prognosis in ESCC patients. Plasma levels of miR-16, miR-21, miR-22, miR-126, miR
      148b, miR-185, miR-221, miR-223, and miR-375 were evaluated by quantitative
      reverse transcriptase polymerase chain reaction (qRT-PCR) assays from 38 ESCC
      patients prior to treatment and 19 healthy subjects. Differences in selected
      miRNAs and their diagnostic and prognostic value were examined. Levels of four of
      the selected miRNAs were found to be significantly higher in ESCC patients than
      in controls; namely, miR-16, miR-21, miR-185, and miR-375 (P < 0.050). In
      addition, the area under the receiver operating characteristic (ROC) curve (AUC)
      for miR-375 was 0.921 (95% confidence interval [CI] 0.817-0.976). Moreover, the
      expression levels of miR-16 were higher in patients with T3-4 tumors than in
      patients with T1-2 tumors (P = 0.020). Kaplan-Meier survival analysis showed that
      high expression levels of miR-16 and miR-21 in the plasma correlated
      significantly with shortened progression-free survival (PFS; P = 0.031 and P =
      0.038, respectively) and overall survival (OS; P = 0.022 and P = 0.041,
      respectively) in ESCC patients. Four plasma miRNAs were identified that could
      potentially serve as novel diagnostic biomarkers for ESCC. Moreover, specific
      miRNAs, such as miR-16 and miR-21, can predict poor survival in ESCC. 

PMID- 26221264
TI  - Microarray-based identification of differentially expressed genes in extramammary
      Paget's disease.
AB  - Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy accounting for
      approximately 1-2% of vulvar cancers. The rarity of this disease has caused
      difficulties in characterization and the molecular mechanism underlying EMPD
      development remains largely unclear. Here we used microarray analysis to identify
      differentially expressed genes in EMPD of the scrotum comparing with normal
      epithelium from healthy donors. Agilent single-channel microarray was used to
      compare the gene expression between 6 EMPD specimens and 6 normal scrotum
      epithelium samples. A total of 799 up-regulated genes and 723 down-regulated
      genes were identified in EMPD tissues. Real-time PCR was conducted to verify the
      differential expression of some representative genes, including ERBB4, TCF3,
      PAPSS2, PIK3R3, PRLR, SULT1A1, TCF7L1, and CREB3L4. Generally, the real-time PCR
      results were consistent with microarray data, and the expression of ERBB4, PRLR,
      TCF3, PIK3R3, SULT1A1, and TCF7L1 was significantly overexpressed in EMPD
      (P<0.05). Moreover, the overexpression of PRLR in EMPD, a receptor for the
      anterior pituitary hormone prolactin (PRL), was confirmed by
      immunohistochemistry. These data demonstrate that the differentially expressed
      genes from the microarray-based identification are tightly associated with EMPD
      occurrence. 

PMID- 26221265
TI  - Sequestrectomy versus microdiscectomy in the treatment of lumbar disc herniation:
      a meta-analysis.
AB  - BACKGROUND: It remains unknown whether sequestrectomy provides better outcomes
      than microdiscectomy for lumbar herniated discs (LHD). Therefore, we conducted a
      meta-analysis to compare the effects of sequestrectomy and microdiscectomy in the
      treatment of patients with LHD. METHODS: Clinical trials published in PubMed,
      Embase, and Web of Science were systematically reviewed to compare the effects of
      sequestrectomy and microdiscectomy for LHD. Outcomes included reherniation rate,
      duration of surgery, length of hospital stay, and postoperative Visual Analog
      Scale (VAS) scales for leg and back pains. A fixed-effects or random-effects were
      used to pool the estimates, depending on the heterogeneity among the studies.
      RESULTS: Five cohorts and two randomized controlled trials (RCTs) with a total of
      929 patients met the inclusion criteria and were included in this meta-analysis.
      All patients underwent sequestrectomy or microdiscectomy. Pooled estimates showed
      that patients treated with sequestrectomy had comparable effects in reherniation
      rate (RR = 1.36, 95% CI: 0.81, 2.27; P = 0.240), length of hospital stay (WMD = 
      0.22 days, 95% CI: -0.45, 0.01; P = 0.060), and postoperative VAS scales for leg
      pain (WMD = 0.53, 95% CI: -1.54, 2.60; P = 0.617) or back pain (WMD = 0.18, 95%
      CI: -1.64, 2.00; P = 0.846), but had a shorter duration of surgery (WMD = -6.97
      minutes, 95% CI: -12.15, -1.78; P = 0.008), when compared with those treated with
      microdiscectomy. CONCLUSION: Based on the current evidence, sequestrectomy
      significantly reduced the operational time, but had similar effects on
      reherniation rate, length of hospital stay, and postoperative VAS scales for leg
      and back pains, when compared with microdiscectomy. Further well-designed
      randomized controlled studies are needed to identify our findings.

PMID- 26221266
TI  - Clinical efficacy of spironolactone for resistant hypertension: a meta analysis
      from randomized controlled clinical trials.
AB  - OBJECTIVES: This study sought to determine the current effectiveness and safety
      of spironolactone for resistant hypertension. METHODS: Pubmed, EMBASE and
      Cochrane databases were searched to identify studies that used spironolactone as
      add-on treatment in resistant hypertension patients. The major outcome is
      reduction of blood pressure. RESULTS: Three randomized controlled trials, 5
      observational study without control group have been identified. At follow-up
      review, there was a reduction in mean systolic and diastolic blood pressure (BP)
      respectively, of -20.56 mmHg (95% confidence interval [CI]: -36.47 to -4.65 mmHg)
      and -6.04 mm Hg (95% CI: -10.24 to -1.85 mm Hg) in controlled study. In
      uncontrolled studies, at 6-month follow-up, systolic and diastolic BP were
      reduced -20.73 mm Hg (95% CI: -25.62 to -15.83 mm Hg) and -8.94 mm Hg (95% CI: 
      10.82 to -7.05 mm Hg, respectively. CONCLUSION: Spironolactone resulted in the
      reduction of mean BP in patients with resistant hypertension. The sustained
      efficacy and safety of spironolactone need to further confirm by large randomized
      controlled trials with long-term follow-up.

PMID- 26221267
TI  - Mannose-capped Lipoarabinomannan from Mycobacterium tuberculosis induces IL-37
      production via upregulating ERK1/2 and p38 in human type II alveolar epithelial
      cells.
AB  - The major surface lipoglycan of Mycobacterium tuberculosis (M. tb), mannose
      capped lipoarabinomannan (ManLAM), is an immunosuppressive epitope of M. tb.
      Interleukin (IL)-37, is a newly identified anti-inflammatory cytokine, which
      reduces systemic and local inflammation. However, the correlation between ManLAM
      and IL-37 remains unknown. Therefore, in this study, we investigate the possible
      role and relative molecular mechanism of ManLAM in IL-37 production of human type
      II alveolar epithelial cells by using A549 cell line. Here, we report that M. tb
      induced IL-37 mRNA and protein expression in a time-dependent manner. We next
      fractionated components of M. tb using chloroform: methanol (C:M) and water. In
      sharp contrast to the C:M phase, water phase was mainly responsible for the
      production of IL-37. Since ManLAM is the major component of water phase, we found
      that ManLAM induced IL-37 mRNA and protein expression in a time and dose
      dependent manner, while this activity was almost totally abolished by the ERK1/2
      (U0126) and p38 (SB203580) inhibitor. ManLAM stimulation significantly induced
      ERK1/2 and p38 phosphorylation in A549 cells, as well as cell surface TLR2
      expression. After interfering TLR2 expression, ERK1/2 and p38 phosphorylation
      levels were markedly decreased, and also IL-37 production. Though ManLAM also
      promoted TLR4 expression on A549 cells, TLR4 interference showed no influence on
      ManLAM-induced IL-37 production. Our results indicate that ManLAM induces IL-37
      production in human type II alveolar epithelial cells via up-regulating TLR2/p38
      or ERK1/2 pathway, and this provide an important evidence to explain the
      pathological role of ManLAM that contribute to the persistence of M. tb. 

PMID- 26221268
TI  - Dendritic cell activation and maturation induced by recombinant calreticulin
      fragment 39-272.
AB  - Dendritic cells (DC) are the most potent antigen-presenting cells for initiating
      immune responses. DC maturation can be induced by exposing of immature DC to
      pathogen products or pro-inflammatory factor, which dramatically enhances the
      ability of DC to activate Ag-specific T cells. In this study, a recombinant
      calreticulin fragment 39-272 (rCRT/39-272) covering the lectin-like N domain and
      partial P domain of murine CRT has been expressed and purified in Escherichia
      coli. Functional analysis studies revealed that rCRT/39-272 has potent
      immunostimulatory activities in both activating human monocytes and B cells to
      secrete cytokines. rCRT/39-272 can drive the activation of bone marrow derived DC
      in TLR4/CD14 dependent way, as indicated by secretion of cytokines IL-12/IL-23
      (p40) and IL-1beta. Exposure of DC to rCRT/39-272 induces P-Akt, suggesting that
      rCRT/39-272 induces maturation of DC through PI3K/Akt signaling pathway. The
      results suggest that soluble rCRT/39-272 is a potent stimulatory agent to DC
      maturation in TLR4/CD14 and PI3K/Akt dependent pathway. It may play important
      roles in initiating cellular immunity in vivo and the T cell response in vitro.
      Thus it could be used for study of DC-based tumor vaccines. 

PMID- 26221269
TI  - Hepatopancreatic intoxication of lambda cyhalothrin insecticide on albino rats.
AB  - BACKGROUND: Despite the known adverse effects of lambda cyhalothrin insecticide,
      little is known about its hepatopancreatic intoxication effects. The present
      study was carried out to elucidate sub-chronic effect of Karat 2.5% EC
      formulation of lambda cyhalothrin on male albino rats. METHODS: To explore the
      effects of exposure to lambda cyhalothrin on rats and its mechanism, low (1/40 of
      LD50, 5 mg/kg/day) and high dose (1/4 of LD50, 50 mg/kg/day) lambda cyhalothrin
      were applied to rats via drinking water for 3 months. Blood samples were
      collected monthly, and the animals were dissected for liver and pancreas's
      examination at the end of the experiment. Lambda cyhalothrin administration was
      associated with the elevation in lipid peroxidation marker, malondialdehyde
      (MDA), reduction in SH-protein a major marker for antioxidant, as well as basel
      paraoxonase (PON) in both treated groups throughout the experimental periods.
      RESULTS: In addition, significant elevations in liver enzymes alanin amino
      transferase, (ALT), and aspartate amino transferase (AST), as well as plasma
      acetylcholinesterase (AChE) and glucose level. While, significant reduction in
      insulin level through the experimental periods. Results of histopathological and
      histochemical studies showed that lambda cyhalothrin exposure induces liver and
      pancreatic tissues damage and depletion in glycogen content was pronounced in
      liver of both treated groups. CONCLUSIONS: In conclusion subchronic intoxication
      with lambda cyhalothrin formulation induced remarkable changes in the examined
      parameters.

PMID- 26221270
TI  - Icariin attenuates glucocorticoid-induced bone deteriorations, hypocalcemia and
      hypercalciuria in mice.
AB  - OBJECTIVE: This study was performed to investigate bone deteriorations and
      calcium homeostasis of GIOP mice in response to the treatment of icariin.
      METHODS: The biomarkers in serum and urine were measured, tibias were taken for
      the measurement on bone calcium, gene expression, histomorphology and micro-CT.
      RESULTS: Glucocorticoid-treated facilitated to induce hypocalcemia and
      hypercalciuria in mice, and icariin-treated showed a greater increase in serum
      calcium and decrease in urine calcium. Icariin reversed DXM-induced trabecular
      deleterious effects and stimulated bone remodeling, including an increase in bone
      calcium, OCN and FGF-23 and a decrease in a critical bone resorption markers CTX
      and TRAP-5b. H&E staining and micro-CT showed the increased disconnections and
      separation among growth plate and trabecular bone network as well as the
      reduction of trabecular bone mass of primary and secondary spongiosa throughout
      the proximal metaphysis of tibia in DXM group. Importantly, icariin reversed DXM
      induced trabecular deleterious effects and stimulated bone remodeling. Moreover,
      the results showed that the mRNA expression of MMP-9 and CAII was significantly
      increased in DXM group compared with control group. Icariin treatment could
      suppress the expression of MMP-9 and CAII in the tibia of mice. CONCLUSIONS: The
      present study demonstrated the protective effects of icariin against bone
      deteriorations, hypocalcemia and hypercalciuria in experimentally DIOP mice.
      Furthermore, these results provided further evidence to support the dual role of
      icariin as a bone formation enhancer and bone resorption inhibitor.

PMID- 26221271
TI  - Toll-like receptor 2 promotes T helper 17 cells response in hepatitis B virus
      infection.
AB  - PURPOSE: Innate and adaptive immune responses play vital roles in initiating and
      maintaining the immunological homeostasis in both physiological and pathological
      processes. However, the expression and function of the important cells and
      molecules as well as their interaction in hepatitis B virus (HBV) infection has
      not been well elucidated. The aim of the current study was to determine the
      pattern of Toll-like receptor 2 (TLR2) in T cells in HBV infection and the
      function of TLR2 in regulation of T helper 17 (Th17) cells response. METHODS:
      Thirty-four patients with HBV infection (ten acute and twenty-four chronic) were
      enrolled. HBV-specific and -nonspecific Th17 cells and TLR2 expression in T cells
      were analyzed by flow cytometry. The function of TLR2 agonist for induction of IL
      17 production was also determined. RESULTS: HBV-specific and -nonspecific IL-17
      secretion in CD4(+) (Th17 cells) and CD8(+) T cells was significantly elevated in
      chronic HBV infection. Viral-specific TLR2 expression in CD4(+), CD8(+), and Th17
      cells was also remarkably increased in patients with chronic hepatitis B.
      Moreover, TLR2 agonist Pam3Csk4 directly activated Th17 cells response without
      antigen stimulation in HBV infection. CONCLUSION: TLR2, which traditionally
      associated with innate immunity, might also promote Th17 cells response in HBV
      infection. The function of TLRs in regulation of adaptive immune response in HBV
      infection, which might play an important role in persistent HBV infection.

PMID- 26221272
TI  - Expression of AKAP95, Cx43, CyclinE1 and CyclinD1 in esophageal cancer and their
      association with the clinical and pathological parameters.
AB  - OBJECTIVE: To investigate correlations among A-kinase anchor protein95 (AKAP95),
      Connexin43 (Cx43), CyclinE1 and CyclinD1 in esophageal squamous cell cancer
      tissues, and their relationship with clinical and pathological parameters.
      METHODS: The protein levels of AKAP95, Cx43, CyclinE1 and CyclinD1 in 54 cases of
      esophageal squamous cell cancer tissues were determined by immunohistochemistry.
      RESULTS: The expression of AKAP95, CyclinE1 and CyclinD1 in esophageal squamous
      cell cancer tissues (53.70%, 88.89%, 72.22%, respectively) was significantly
      increased when compared to pericarcinoma tissues (20.00%, P < 0.05; 6.67%, P <
      0.01; and 20.00%, P < 0.05; respectively). By contrast, Cx43 expression in
      esophageal squamous cell cancer tissues (22.22%) was lower than that in
      pericarcinoma tissues (60.00%, P < 0.05). The expression of AKAP95, Cx43,
      CyclinE1 and CyclinD1 in the tissues of esophageal squamous cell carcinoma was
      unrelated to lymph node metastasis and the degree of differentiation. The
      expression of Cx43, CyclinE1, CyclinD1 in the tissues of esophageal squamous cell
      carcinoma was significantly correlated with AKAP95, respectively (P < 0.05).
      CONCLUSION: Expression levels of AKAP95, CyclinE1 and CyclinD1 were higher, and
      that of Cx43 lower in esophageal squamous cell carcinoma tissues as compared
      pericarcinoma tissues, which suggests their importance in the incidence and
      development of esophageal squamous cell carcinoma. The expression of Cx43,
      CyclinE1, CyclinD1 in the tissues of esophageal squamous cell carcinoma was
      correlated with AKAP95, respectively. The expression of AKAP95, Cx43, CyclinE1
      and CyclinD1 in the tissues of esophageal squamous cell carcinoma was unrelated
      to the degree of differentiation and lymph node metastasis.

PMID- 26221273
TI  - Cordyceps sinensis preserves intestinal mucosal barrier and may be an adjunct
      therapy in endotoxin-induced sepsis rat model: a pilot study.
AB  - BACKGROUND: Cordyceps sinensis (C. sinensis), a traditional Chinese medicine,
      exhibits various pharmacological activities such as reparative, antioxidant, and
      apoptosis inhibitory effects. Intestinal barrier dysfunction plays a vital role
      in the progression of sepsis. We aimed to explore the effect of C. sinensis on
      the gut barrier and evaluate its efficacy in sepsis. METHODS: A murine model of
      gut barrier dysfunction was created by intraperitoneal injection of endotoxin. C.
      sinensis or saline was administered orally after the induction of sepsis.
      Alterations of intestinal barrier were evaluated and compared in terms of
      epithelial cell apoptosis, proliferation index (PI), intercellular tight junction
      (TJ) and proliferating cell nuclear antigen (PCNA). RESULTS: C. sinensis
      significantly decreased the percentage of apoptotic cells and promoted mucosal
      cells proliferation indicated by enhanced PI and PCNA expression in the
      intestinal mucosa compared to control group. The TJs between epithelial cells
      which were disrupted in septic rats were also restored by treatment of C.
      sinensis. In survival studies, C. sinensis was demonstrated to confer a
      protection against the lethal effect of sepsis. CONCLUSION: These results suggest
      that C. sinensis has gut barrier-protection effect in endotoxin-induced sepsis by
      promoting the proliferation and inhibiting the apoptosis of intestinal mucosal
      cells, as well as restoring the TJs of intestinal mucosa. C. sinensis may have
      the potential to be a useful adjunct therapy for sepsis.

PMID- 26221274
TI  - Lymphocele: a clinical analysis of 19 cases.
AB  - PURPOSE: To summarize the clinical manifestations, diagnosis, and treatment of
      lymphocele. MATERIALS AND METHODS: 19 cases of lymphocele diagnosed by
      postoperative pathology from January 2003 to September 2012 were retrospectively
      analyzed, especially the general information, clinical manifestations, imaging,
      operations, and pathological findings. RESULTS: In 19 cases, the common locations
      were in retroperitoneal, abdominal wall, and neck. There were no typical clinical
      manifestations with lymphocele. 6 cases visited hospital because of pain, while
      13 cases were diagnosed incidentally with imaging or surgery. Fourteen cases
      undergoing CT were all displayed as cystic lesion. In 12 of 14 cases undergoing
      type-B ultrasonic, the masses were shown to be cystic lesion without special
      signs. 19 cases were all treated by surgical resection, and testified to be
      lymphocele with pathological analysis. The sensitivity of D2-40 was 89.5% (17/19)
      in our study. CONCLUSIONS: Lymphocele is very rare with no specific clinical
      manifestations. The preoperative diagnosis was based on imaging examinations,
      while definite diagnosis was based on the pathological, and (or)
      immunohistochemical examination with D2-40. The prognosis of lymphocele is good
      after it is removed completely.

PMID- 26221275
TI  - Klotho: a novel and early biomarker of acute kidney injury after cardiac valve
      replacement surgery in adults.
AB  - Klotho is a potential biomarker and therapeutic target in a model of acute kidney
      injury (AKI) induced in rats by ischemia-reperfusion injury. However, the
      sensitivity and specificity of serum Klotho for early detecting clinical AKI are
      unknown. This prospective study evaluated the significance of serum Klotho for
      early detection of postoperative AKI among adult patients undergoing cardiac
      valve replacement surgery. Moreover, we also compared the utilities of serum
      Klotho, serum creatinine and cystatin C in early detection of AKI. There was no
      marked difference between AKI and non-AKI groups in preoperative serum Klotho
      levels. Immediately after the operation, serum Klotho decreased significantly in
      patients with AKl. In spite of the poor specificity, its diagnostic sensitivity
      was excellent. On postoperative 1 d, with the rapid recovery toward the
      preoperative level, the ability of serum Klotho for early detecting AKI declined.
      Changes in serum Klotho levels at every time point among patients without AKI did
      not reveal any statistical significance. We showed that AKI is a state of
      transient Klotho deficiency in patients undergoing cardiac valve replacement
      surgery. Serum Klotho levels were drastically decreased beginning at 0h with
      ideal ROC-AUC, sensitivity but poor specificity, which didn't exceed 4 h after
      operation, suggesting that serum Klotho could serve as a potential biomarker for
      CSA-AKI, especially during the short period after cardiac surgery. A larger
      multicentre cohort study of population in different ages undergoing on-pump
      cardiac surgery is required to identify the optimal timing of serum Klotho
      measurement and the optimal cut-off points for clinical use to further refine the
      optimal timing for early detection of AKI. 

PMID- 26221276
TI  - Reduced incidence of postoperative symptoms following a novel bilateral
      supraclavicular approach to open thyroidectomy: a randomized clinical trial in a
      Chinese population.
AB  - Transient postoperative symptoms, including pain, swelling, unnatural feelings
      during cervical movements, and incision adhesion formation are common in patients
      after open thyroidectomy, especially in those with bilateral lesions. Therefore,
      we proposed a new bilateral supraclavicular approach to reduce such
      complications, and compared it with the conventional transcervical approach to
      verify its safety and efficacy. Forty-four patients were recruited and randomized
      into either a conventional transcervical group (CT) or a bilateral
      supraclavicular (BS) group. Surgically-related variables, duration of
      postoperative symptoms, and incision adhesion formation status were recorded and
      evaluated. There were no statistically significance differences in sex, age,
      extent of surgery, pathological type, intraoperative blood loss, and operation
      duration between the two groups. The BS group had a slightly longer total
      incision length, but exhibited a significantly shorter period of postoperative
      symptoms (P=0.012) and lower risk for adhesion formation (P=0.035 in the 1st
      month, P=0.047 in the 10th month) compared to the CT group. In conclusion, the
      bilateral supraclavicular approach is a safe and effective method for reducing
      postoperative symptoms and adhesion formation in patients with bilateral thyroid
      lesions. 

PMID- 26221277
TI  - Acidic extracellular microenvironment promotes the invasion and cathepsin B
      secretion of PC-3 cells.
AB  - BACKGROUND: This study aimed to investigate the effect of acidic microenvironment
      on the invasion of prostatic carcinoma PC-3 cells and to explore the potential
      mechanism. MATERIAL AND METHODS: PC-3 cells were maintained in medium at
      different pHs (pH 7.4, pH 7.0 and pH 6.6). Invasion and metastasis of PC-3 cells
      were investigated in vitro. Acridine orange staining was performed, followed by
      laser confocal scanning microscopy for the localization of lysosomes. Western
      blot assay and ELISA were employed to evaluate the effect of acidic
      microenvironment on the cathepsin B secretion. RESULTS: Acidic microenvironment
      remarkably promote the invasion and migration of PC-3 cells (P<0.01). Moreover,
      at acidic extracellular pH (pHe), an obvious shift of lysosomes from the
      perinuclear region to the periphery was observed. Western blot assay and ELISA
      revealed that acidic microenvironment promoted the cathepsin B secretion in PC-
      cells. CONCLUSION: Acidic microenvironment may significantly promote the invasion
      of PC-3 cells and increase the secretion of cathepsin B. This suggests that the
      acidic microenvironment induced invasion of PC- cells is related to the elevated
      cathepsin B secretion.

PMID- 26221278
TI  - Effect of semisynthetic extracellular matrix-like hydrogel containing hepatocyte
      growth factor on repair of femoral neck defect in rabbits.
AB  - Using tissue engineering technology research to develop organized artificial
      bone, then repair bone defect. This work aims to investigate the role of
      semisynthetic extracellular matrix-like hydrogel (sECMH) containing hepatocyte
      growth factor (HGF) on repair of femoral neck defect in rabbits. 18 New Zealand
      rabbits were used in this study. According to autologous paired comparison
      method, the left and right sides of rabbit were used as control and experimental
      side, respectively. The models of bilateral femoral neck bone defect were
      established. In experimental side, sECMH containing HGF was implanted in the
      defect area. In control side, no material was implanted in the defect area. At
      the 2nd, 4th and 8th week after surgery, the gross observation, histological
      examination and molybdenum target (Mo-target) X-ray examination were performed on
      the specimens to study the repair of femoral neck defect. In gross observation,
      there was no macroscopic difference of femoral neck specimen between the 2nd and
      4th postoperative week. At the 8th week, the defect orifice was closed with
      immature cortical bone, with unblocked marrow cavity. HE staining results showed
      that, at the 4th week, there were more new vessels in defect area of experimental
      side, compared with control side. At the 8th week, in experimental side there was
      immature cortical bone connecting the fracture end in defect area, with visible
      bone marrow cells. Mo-target X-ray examination found that, at the 8th week, the
      bone tissue repair in experimental side was better than control side. As a new
      drug delivery system, sECMH containing HGF has good application prospect in bone
      tissue repair. 

PMID- 26221279
TI  - Inhibition of breast cancer cell proliferation by a newly developed
      photosensitizer chrolophyll derivative CPD4.
AB  - To investigate the mechanism of inhibition of breast cancer cell proliferation by
      a newly developed photosensitizer chrolophyll derivative CPD4. MCF-7 cells were
      treated with CPD4 in different concentrations for 2 h, followed by irradiation
      (670 nm, 10 J/cm(2)) using a semiconductor laser. Apoptotic mode and ratio of
      treated cells were analyzed. Subcellular localization of CPD4 were observed.
      Mitochondrial membrane potential was measured, and expression of Bcl-2 and Bax
      was detected. Four groups were set in this study: (1) no photosensitizer or light
      irradiation treatment, (2) photosensitizer (2.5 MUg/mL CPD4) alone, (3) light
      irradiation alone, and (4) combined photosensitizer and light irradiation
      treatment (2.5 MUg/mL CPD4-PDT). Flow cytometry assays revealed that apoptotic
      ratio of CDP4-PDT treated cells increased significantly in a CDP4 dose-dependent
      manner whereas apoptotic and necrotic ratio in the control group was only 4.9%
      6.2% and 1.3%-2.9%, respectively. CPD4 was primarily distributed in mitochondria.
      While no significant difference in mitochondrial membrane potential was observed
      among three control groups (BG, PG and IG group) (P<0.05), mitochondrial membrane
      potential in CDP4-PDT group decreased significantly after irradiation treatment
      (P>0.05). A simutanous downregulation of Bcl-2 protein and overexpression of Bax
      protein in CDP4-PDT treated cells led to a reduction in the Bcl-2/Bax ratio. CPD4
      photodynamic treatment induced decreased mitochondrial membrane potential, and
      might thereby trigger apoptosis through mitochondrial pathway in MCF-7 cells. The
      treatment stimulated Bcl-2 expression but down-regulated Bax expression, which
      might suggest an alternative mechanism of apoptotic effect of CPD4. 

PMID- 26221280
TI  - Snail promotes epithelial-mesenchymal transition and invasiveness in human
      ovarian cancer cells.
AB  - There are limited reports with respect to the study on the epithelium-mesenchymal
      transformation (EMT) mediated by Snail in the ovarian cancer. This study detected
      the expression of Snail and related EMT markers in the ovarian cancer tissues,
      and explored the possible molecular mechanism of EMT mediated by Snail in the
      metastasis of ovarian cancer. The patients diagnosed with ovarian cancer
      according to the pathology were recruited in this study during 2010-2014. The
      carcinoma tissue and normal tissue adjacent to carcinoma were surgically obtained
      from patients. The genes of E-cadherin, beta-catenin, Fibronectin and N-cadherin
      were detected using the RT-PCR. The 64 patients were recruited and diagnosed as
      ovarian cancer by pathological examination. The expression levels of Snail,
      Fibronectin and N-cadherin in the stage III and IV were higher than those in the
      stage I and II, respectively (all P < 0.05). However, the expression levels of E
      cadherin and beta-catenin decreased along with the stage developed (trend test,
      both P < 0.05), respectively. The expression of Snail was positively correlated
      with the expression of Fibronectin, N-cadherin, but negatively correlated with
      the expression of E-cadherin and beta-catenin. The number of A2780 cells entering
      into the lower compartment in the group of carcinoma tissue were significantly
      higher than that in the group of normal tissue after transfected with Snail
      expression vector. While, the invasion ability of A2780 significantly reduced
      after RNAi-Snail. The correlation between Snail and invasion and metastasis of
      ovarian cancer and epithelial-mesenchymal transition based on tissue and cell
      levels, and to some extent explored the molecular mechanism of the EMT process
      mediated by Snail. 

PMID- 26221281
TI  - 50 Hz electromagnetic field exposure promotes proliferation and cytokine
      production of bone marrow mesenchymal stem cells.
AB  - OBJECTIVE: To investigate the effects of extremely low frequency electromagnetic
      field (ELF-EMF) on the proliferation and cytokine production of mesenchymal stem
      cells (MSC) and the effects of mesenchymal stem cell conditioned medium (MSC-CM)
      on the proliferation and migration of macrophagocytes (RAW264.7). METHODS: Bone
      marrow derived-mesenchymal stem cells (rBMSC) were isolated from rats, cultured
      and randomly divided into two groups: SHAM group (absence of electromagnetic
      field exposure) and EMF group. Cells in EMF group were exposed to ELF-EMF (50 Hz,
      1 mT, 4 h/d) under sXc-ELF. Mouse mesenchymal stem cells (mMSC) were exposed to
      EMF for 3 days. RESULTS: The cell viability, DNA synthesis and proportion of
      cells in S phase in EMF group increased markedly when compared with SHAM group
      (P<0.05). When compared with SHAM group, the mRNA expressions of M-CSF and SCF
      increased markedly at 2 days after EMF exposure (P<0.05), the mRNA expressions of
      SCF, M-CSF, TPO, LIF, IL-11 and IL-7 increased dramatically, but the mRNA
      expressions of IL-6, SDF-1, IFN-gamma and TNF-alpha remained unchanged (P>0.05)
      in mMSCs at 3 days after EMF exposure. In EMF group, the viability of RAW264.7
      after MSC-CM treatment increased markedly as compared to SHAM group (P<0.05), and
      the ability to migrate of RAW264.7 after MSC-CM treatment in EMF group also
      increased significantly when compared with SHAM group (P<0.05). CONCLUSION: EMF
      is able to promote the proliferation of rBMSCs, up-regulate the expressions of
      hematopoietic growth factors in rBMSC and mMSC and increase the mMSC induced
      proliferation and migration of RAW264.7.

PMID- 26221282
TI  - Anatomy-related risk factors for the subsidence of titanium mesh cage in cervical
      reconstruction after one-level corpectomy.
AB  - To clarify anatomy-related risk factors in the cervical spine with subsidence of
      titanium mesh cage (TMC) after one-level cervical corpectomy and fusion, we have
      assessed the radiological examinations and clinical outcomes for 236 patients.
      All the patients were underwent one-level corpectomy and TMC fusion between
      August 2003 and March 2006. The effects of the cervical posture, segmental
      curvature and endplate gradient on the postoperative phenomenon for these
      patients were evaluated. Our results suggested that in the patients who were
      followed up for 12 months, TMC subsidence occurred in 54 (28.6%) cases. C6
      corpectomy had a significant higher risk (26/60, 43.3%) for TMC subsidence, which
      was correlated with the variation of the gradient of the vertebral endplates
      against cervical levels. Although the clinical outcome was comparable with those
      in the literature, the patients may have subsidence-related problems such as neck
      shoulder pain, neurological deterioration and instrumental failure. In
      conclusion, to reduce the incidence of subsidence, TMC design should be optimized
      to be in line with anatomic characteristics of the cervical spine. 

PMID- 26221283
TI  - Association of COX-2 -765G>C genetic polymorphism with coronary artery disease: a
      meta-analysis.
AB  - BACKGROUND: Previous studies suggested the single nucleotide polymorphism (SNP)
      of COX-2 -765G>C (rs20417) is associated with coronary artery disease (CAD), but
      the results were conflicting. In order to derive a more precise estimation of the
      associations, we performed a meta-analysis of the relationship between rs20417
      and CAD in all published studies. METHOD: Databases including PubMed, Web of
      Science, Wanfang, SinoMed and CNKI were systematically searched. Data were
      extracted using standardized methods. The association was assessed by odds ratio
      (OR) with 95% confidence intervals (CIs).The statistical tests were performed
      using Review Manager 5.3.3 and Stata 12.0 software. RESULTS: We identified a
      total of 14 studies involving a total of 18227 subjects. The pooled odds ratio
      (OR) for the association between COX-2 -765G>C and CAD and its corresponding 95%
      confidence interval (95% CI) were evaluated by random or fixed effect model. A
      significant statistical association between COX-2 -765G>C and CAD was observed in
      an allelic model (P=0.02, OR=0.64, 95% CI: 0.43-0.94), dominant model (P=0.04,
      OR=0.74, 95% CI: 0.56-0.99), and recessive model (P=0.02, OR=0.46, 95% CI: 0.23
      0.90). CONCLUSION: This meta-analysis suggested that COX-2 -765G>C is a
      protective for CAD.

PMID- 26221284
TI  - A novel mutation in fibrillin-1 gene identified in a Chinese family with marfan
      syndrome.
AB  - Marfan syndrome (MFS) is an autosomal dominant inheritary disorder of the
      connective tissue. We report clinical features of a Chinese family with MFS and
      identify mutations in fibrillin-1 gene (FBN1). In this study, all three members
      of this family underwent complete ophthalmologic examinations. Two of the three
      members were diagnosed with MFS. Molecular genetic analysis was performed on the
      three members. All coding exons of FBN1 were amplified by polymerase chain
      reaction (PCR). The amplified products were sequenced and compared with a
      reference sequence in the database. Possible structural and functional changes of
      the protein induced by amino acids variance were predicted by bioinformatic
      analysis. A novel heterozygous mutation c.4504 T>A (p.C1502S) in exon 36 was
      identified in the two affected members, but not in the unaffected member. To our
      knowledge, this FBN1 mutation has not been reported beforein MFS or other
      patients. 

PMID- 26221285
TI  - Biological effects of ray cartilage extract on human breast cancer cell line MCF
      7 and its mechanism.
AB  - OBJECTIVE: To explore the biological effects of ray cartilage extract (RCE) on
      human breast cancer cell line MCF-7 and its mechanism. METHODS: MCF-7 cells were
      treated with RCE of different concentrations for different durations, and then
      MCF-7 cell proliferation was evaluated with MTT test, cell cycle was detected
      with flow cytometer and the protein levels of cyclin D1 and p21 were determined
      with Western blot. RESULTS: MTT test indicated that MCF-7 cell proliferation was
      inhibited by RCE with an optimal inhibiting concentration of 10 MUmol/L and an
      optimal action time of 48 h. Flow cytometer displayed that with the time
      prolongation of RCE action, the cells in S phase were significantly increased,
      but the cells in G2/M phase were significantly decreased; and MCF-7 apoptosis
      significantly increased as compared with blank control group (all P<0.05).
      Western blot found that with the time prolongation of RCE action, the level of
      cyclin D1 was significantly decreased, but the level of p21 was significantly
      increased as compared with blank control group (all P<0.05). CONCLUSION: RCE
      inhibits MCF-7 cell proliferation via arresting MCF-7 cell transformation from S
      phase to G2 phase. This may be associated with regulating the expressions of
      cyclin D1 and p21. RCE may be used as a drug for treatment of breast cancer in
      the future.

PMID- 26221286
TI  - Association between serum interleukin-35 levels and severity of acute
      pancreatitis.
AB  - Inflammatory cytokines have been reported to be associated with pathogenesis of
      acute pancreatitis. The aim of this study was to measure the serum IL-35 levels
      in patients with acute pancreatitis and analyze the relationship between IL-35
      levels and the disease severity. Thirty-two patients with acute pancreatitis and
      32 healthy control subjects were included into the study. The serum levels of IL
      35 were measured by enzyme-linked immunosorbent assay upon admission and the
      following seven days. The relationships with severity and etiology during the
      clinical course were analyzed. Serum IL-35 levels in patients with acute
      pancreatitis at the time of admission (5.25+/-0.37 ng/mL) were significantly
      higher than those in healthy controls (1.93+/-0.16 ng/mL, P<0.001). Moreover,
      serum IL-35 levels in patients with severe attacks (7.15+/-0.48 ng/mL) were
      significantly higher than those with moderately severe attacks (5.14+/-0.49
      ng/mL, P=0.01) and mild attacks (3.69+/-0.53 ng/mL, P<0.001). However, there was
      no significant difference of serum IL-35 levels among patients with acute
      pancreatitis due of alcohol, gallstone and idiopathy. In addition, the peak serum
      concentrations of IL-35 were on day 1 after admission. Our results demonstrate
      that increased serum IL-35 levels may be related to the inflammatory response in
      patients with acute pancreatitis, suggesting that IL-35 may be used for a
      potential biomarker of acute pancreatitis. 

PMID- 26221287
TI  - Expression of CXCR4 and non-small cell lung cancer prognosis: a meta-analysis.
AB  - PURPOSE: The prognostic value of aberrant C-X-C chemokine receptor type 4 (CXCR4)
      levels in NSCLC has been described in empirical studies. This meta-analysis
      evaluates the value of CXCR4 as a prognostic marker for NSCLC and determines the
      relationship between CXCR4 and clinicopathological features of NSCLC. METHODS: A
      comprehensive search of the English-language literature in PubMed, Embase, Google
      Scholar and Web of Science was performed. Articles containing sufficient
      published data to determine an estimate of the hazard ratio (HR) and a 95%
      confidence interval (95% CI) for over survival (OS) or disease-free survival
      (DFS) were selected. Of 417 potentially relevant studies, 10 eligible studies
      (1,334 NSCLC patients) met the inclusion criteria. RESULTS: Overall, high CXCR4
      expression was significantly associated with a poor OS rate (HR=1.59, 95% CI=1.36
      1.87, P<0.001) while the association with DFS was not statistically significant
      (HR=1.00, 95% CI=0.37-2.69, P=0.993). Stratified analysis by subcellular
      localization found that CXCR4 overexpression in the non-nucleus predicts poor OS
      (HR=1.65, 95% CI=1.40-1.95, P<0.001) and DFS (HR=3.06, 95% CI=2.15-4.37,
      P<0.001), but elevated CXCR4 expression in the nucleus was positively associated
      with DFS (HR=0.44, 95% CI=0.26-0.75, P=0.002). NSCLC patients with CXCR4
      expression were more likely to be diagnosed with adenocarcinoma cancer (OR=1.45,
      95% CI=1.07-1.95, P=0.016), lymph node involvement (OR=0.69, 95% CI=0.50-0.96,
      P=0.027), and distant metastasis (OR=0.36, 95% CI=0.14-0.93, P=0.035).
      CONCLUSION: Aberrant overexpression of CXCR4 is associated with worse overall
      survival, adenocarcinoma histology, distant metastasis, lymph node involvement in
      NSCLC.

PMID- 26221288
TI  - Hepatitis C virus (HCV) genotype 2a has a better virologic response to antiviral
      therapy than HCV genotype 1b.
AB  - The standard treatment, pegylated interferon (PEG-IFN) plus ribavirin (RBV), for
      patients with chronic hepatitis C (CHC), does not provide a sustained virologic
      response (SVR) in a large majority of patients. In the present study, 211
      treatment-naive patients with the hepatitis C virus (HCV) genotype 1b and 2a were
      recruited and treated weekly with PEG-IFN plus RBV to determine the response of
      HCV genotype 1b and 2a patients to standard antiviral treatment. Virologic
      responses were assessed by TaqMan at week 4, 12, 24, 48 and 24 weeks of
      treatment. Patients with HCV genotype 2a had a significantly higher rapid
      virologic response (RVR), early virologic response, end-of-treatment response and
      SVR, and a lower relapse rate than patients with HCV genotype 1b. Multivariate
      logistic regression analysis showed that the HCV genotype 2a patients had a HCV
      RNA level <= 5.70 log10 IU/ml, a fibrosis stage < S3, and that HLA-A02 expression
      and RVR were independent factors of SVR that may improve HCV clearance. 

PMID- 26221289
TI  - Endovascular intervention for delayed post-pancreaticoduodenectomy hemorrhage:
      clinical features and outcomes of transcatheter arterial embolization and covered
      stent placement.
AB  - Delayed post-pancreaticoduodenectomy hemorrhage (PPH) is a rare but life
      threatening complication with high mortality. In this retrospective study, we
      aimed to evaluate the safety, efficacy and utility of interventional treatment of
      delayed PPH. From January 2008 to December 2013, 357 patients underwent
      pancreaticoduodenectomy (PD). 21 patients (5.9%) suffered from the delayed PPH.
      18 patients underwent diagnostic angiography and endovascular treatment, either
      transcatheter arterial embolization (TAE, n = 10) or covered stent placement
      (CSP, n = 8), and 3 patients underwent laparotomy. The mean time of hemorrhage
      was 21.4 days. In 10 patients received TAE treatments, 3 got liver damage and 2
      presented liver abscesses with 1 died of severe infection and multi-organ
      failure. Re-bleeding was occurred in 4 of 10 TAE patients. 8 patients received
      CSP got thoroughly bleeding control and without any ischemic or re-bleeding
      complications. 2 of 3 laporotomy patients presented hemorrhage recurrence. In all
      6 re-bleeding patients, 2 were saved by CSP, while the other 4 died (TAE in 3 and
      conservative treatment in 1). Early intervention plays an important role of
      saving patients from delayed PPH. The CSP is considered a fist-line treatment for
      delayed PPH and an appropriate solution for hemorrhage recurrence. TAE only could
      be performed in whom placing a covered stent is technically difficult. 

PMID- 26221290
TI  - Multimodal imaging and clinical characteristics of bone lesions in POEMS
      syndrome.
AB  - POEMS syndrome is a rare plasmacyte-associated disease, one of the major
      diagnostic criteria of which is sclerotic bone lesion. To detect bone lesions in
      POEMS syndrome, which imaging method should be routinely applied and what
      characteristics they display are still unconfirmed. We analyzed clinical data and
      imaging characteristics of bone lesions in 22 patients with POEMS using
      multimodal methods, including conventional X-ray, computed tomography (CT),
      magnetic resonance imaging (MRI), and positron emission tomography/computed
      tomography (PET/CT). Images on X-ray and CT exhibited plaque-like high-density
      for osteosclerotic lesions and punched-out low-density appearance for osteolytic
      ones. X-ray had advantage in detecting bone lesions in skull, extremity long
      bones, clavicle, and scapula, while CT could display sharp outline of lesions and
      was more sensitive than X-ray in detecting the small lesions. Osteosclerotic
      lesions on MRI demonstrated decreased signal intensity on both T1 and T2-weighted
      sequences, while osteolytic lesions or osteolytic part of mixed lesions showed
      high signal intensity on T2-weighted sequences. MRI had same sensitivity as CT,
      but with superiority in distinguishing the active osteolytic lesions from the
      osteosclerotic ones. PET-CT showed (18)F-FDG uptake was normal in the majority of
      osteosclerotic lesions, and slightly increased in mixed ones, but obviously
      elevated in osteolytic ones. PET/CT was less sensitive in detecting
      osteosclerotic lesions than in detecting osteolytic ones. In conclusion, to
      detect bone lesions in POEMS, conventional X-ray scan should be first performed,
      further followed by more sensitive CT or MRI. PET-CT is optional when the
      osteolytic lesions are suspected. 

PMID- 26221291
TI  - Clinical analysis of infarction in pituitary adenoma.
AB  - OBJECTIVES: This study is to summarize the clinical manifestations, imaging
      findings, treatment and prognosis of pituitary apoplexy caused by ischemic
      infarction. METHODS: From January 2010 to March 2014, 412 patients with pituitary
      adenoma were admitted in the Department of Neurosurgery at Fuzhou General
      Hospital, with 9 cases being diagnosed with ischemic infarction stroke. Imaging
      examinations were performed, including computed tomography and magnetic resonance
      imaging. Pituitary adenomas were evaluated according to suprasellar, infrasellar,
      parasellar, anterior and posterior classification. Hematoxylin and eosin staining
      and immunohistochemical staining were used for identifying pituitary adenoma.
      RESULTS: Tumor height was 1.3-3.3 cm, with an average of 2.27 cm. Eight patients
      had typical clinical stroke symptoms. Preoperatively, high blood growth hormone
      concentration was presented in 6 cases, full hypopituitarism in 2 cases,
      dysfunction of corticosteroids and gonads in 4 cases, and single gonadal
      dysfunction in 2 cases. Ring enhancement was presented in 8 cases on constructed
      computed tomography or magnetic resonance images, and sellar settlement in 7
      cases. Eight patients were conducted with transsphenoidal resection, and
      secondary transsphenoidal after craniotomy in 1 case. During surgery, poor tumor
      blood supply was found in 7 cases, cheese-like or tofu-like necrotic tissues in 5
      cases, and few dark blood clots in 2 cases. CONCLUSIONS: Pituitary ischemic
      infarction stroke is clinically rare, but can be correctly diagnosed before
      surgery by imaging examinations. The pathological characteristics of the tumor
      are necrosis and fibrosis, which are easy for resection. Therefore, pituitary
      adenoma usually has good prognosis.

PMID- 26221292
TI  - Relationship between NOX4 level and angiotensin II signaling in Gitelman's
      syndrome. Implications with hypertension.
AB  - Recent evidence showed that endogenous nicotinamide adenine dinucleotide
      phosphate-oxidase 4 (NOX4) may exert a protective role on the cardiovascular
      system inducing vasodilation, reduction of blood pressure, and anti-proliferative
      actions. However, the functional significance of NOX4 in the cardiovascular
      system in humans remains elusive. Mononuclear cell levels of NOX4 were assessed
      by immunoblotting in 14 Gitelman's patients (GS), a unique human model of
      endogenous Ang II signaling antagonism and activation of anti-atherosclerotic and
      anti-remodeling defenses, and compared to 11 untreated essential hypertensive
      patients as well as to 11 healthy normotensive subjects. The association between
      NOX4 and its effector heme oxygenase (HO-1) (sandwich immunoassay) was also
      evaluated. NOX4 protein levels were decreased in hypertensive patients as
      compared to both GS and healthy subjects (1.06+/-0.31 AU vs. 1.76+/-0.54, P=0.002
      and vs. 1.61+/-0.54, P=0.018, respectively). NOX4 protein level did not differ
      between GS and healthy subjects. HO-1 levels were increased in GS patients as
      compared to both hypertensive patients and healthy subjects (8.65+/-3.08 ng/ml vs
      3.70+/-1.19, P<0.0001, and vs 5.49+/-1.04, P=0.008, respectively. NOX4 levels
      correlate with HO-1 levels only in GS (r(2)=0.63; P=0.001), (r(2)=0.088; P=ns, in
      hypertensive patients and r(2)=0.082; P=ns, in healthy subjects). Our findings
      show that NOX4 and its effector HO-1 are reduced in hypertensive patients
      compared to GS patients, a human model opposite to hypertension. Although the
      functional significance of NOX4 needs further clarification, our preliminary data
      in a unique human model of anti-atherosclerotic and anti-remodeling defenses
      activation, highlight the potentially protective role of NOX4 in the human
      cardiovascular system. 

PMID- 26221293
TI  - Association analysis of GWAS and candidate gene loci in a Chinese population with
      coronary heart disease.
AB  - OBJECTIVE: Coronary heart disease (CHD), the most severe form of coronary artery
      disease (CAD), is a complex disease that involves a variety of genetic and
      environmental factors. Recently, multiple single nucleotide polymorphisms (SNPs)
      have been associated with CAD in Caucasians by genome-wide association (GWA)
      studies.However, the association of these SNPs with CHD in Asian populations has
      not yet been established. Here, we aim to investigate the genetic etiology of CHD
      in a Chinese population by genotyping SNPs previously been associated with CHD in
      other ethic origin in GWAS or candidate gene studies. METHODS: Five SNPs,
      rs17114036, rs9369640, rs515135, rs579459 and rs8055236, from 5 different loci
      were genotyped using a sequenom Mass array system in 545CHD patients and 1008
      unrelated controls from a Chinese population. RESULTS: Our study showed that SNP
      rs515135 is strongly associated with CHD in a Chinese Han population (P
      value=0.00333, OR=1.48). We also detected significant difference of SNP rs579459
      in APOB gene in patients withsevere CAD compared to patients with mild CAD.
      CONCLUSION: SNP rs515135 is associated with the susceptibility of CHD in Chinese
      Han population. The location of rs515135 in the APOB gene supports its potential
      involvement in the pathogenesis of CAD. Our study data also support that SNP
      rs579459 may be associated with the severity of CHD.

PMID- 26221294
TI  - The therapeutic effect of Xueshuan Xinmai tablets on memory injury and brain
      activity in post-stroke patients: a pilot placebo controlled fMRI study.
AB  - OBJECTIVE: The purpose of this study was to explore the effects of Xueshuan
      Xinmai tablets (XXMT) for the treatment of cognition, brain activation in the
      rehabilitation period of ischemic stroke patients. METHODS: 28 adults patients,
      aged 50-80 years, in the rehabilitation period of ischemic stroke were divided
      into XXMT treatment group and placebo control group. Patients received 3 months
      treatment (oral 0.8 g, 3 times per day). Before and after treatment, all patients
      were evaluated by a series of neuropsychological tests followed by resting-state
      functional magnetic resonance imaging (fMRI). RESULTS: In the XXMT treatment
      group, the patients' episodic memory showed significant improvement. The resting
      state fMRI analysis indicated that a significant decline in the fractional
      amplitude of low-frequency fluctuation value was observed in the bilateral middle
      cingulate gyrus. CONCLUSIONS: Yiqi Huoxue effect under XXMT administration has a
      favorable mediation on episodic memory, consequently suppresses the activation of
      the cingulate gyrus in the rehabilitation period of ischemic stroke patients.

PMID- 26221295
TI  - Endovascular management of giant middle cerebral artery aneurysms.
AB  - BACKGROUND: This article reported the experience of endovascular treatment in
      giant middle cerebral artery (MCA) aneurysms with parent artery occlusion or
      stent-assisted coiling. MATERIAL AND METHODS: Eleven consecutive patients with
      giant MCA aneurysms were included. The aneurysms predominantly involved the M1
      segment in two cases, bifurcation in four cases, and M2 in five cases. Four M2
      fusiform aneurysms were treated with parent artery sacrifice after balloon
      occlusion test. The seven unruptured aneurysms and one ruptured one were treated
      with stent-assisted coiling. The post-operation and long-term follow-up
      angiographic and clinical outcomes were analyzed. RESULTS: Endovascular coiling
      was performed successfully in all 11 cases. All four M2 fusiform cases using
      parent artery occlusion strategy achieved complete occlusion of aneurysms. In the
      seven cases with stent-assisted coiling, four were completely occluded, two were
      partially occluded and one remained small residue. Mild perioperative
      complications occurred in six patients. The follow-up angiography taken at a mean
      of 13.5 months of eight patients showed that seven aneurysms remained stable or
      improved and one M1 aneurysms relapsed and needed further treatment. CONCLUSION:
      Stent-assisted coiling or parent artery occlusion of selected giant MCA aneurysms
      is an option to consider.

PMID- 26221296
TI  - MicroRNA-H4-5p encoded by HSV-1 latency-associated transcript promotes cell
      proliferation, invasion and cell cycle progression via p16-mediated PI3K-Akt
      signaling pathway in SHSY5Y cells.
AB  - Herpes simplex virus 1 (HSV-1) microRNAs (miRNAs) mostly located in transcription
      associated transcript (LAT) region have been identified that play critical roles
      in the intricate host-pathogen interaction networks. Increasing evidences throw
      new insight into the role of miRNA-mediated miRNA-mRNA cross-talk in HSV-1 latent
      or acute infection. In the present study, we found that hsv-1 miR-H4-5p (here
      termed as miR-H4b) can down-regulate the expression of cyclin-dependent kinase
      inhibitor 2A (CDKN2A, p16) in neuroblastoma (SHSY5Y) cell lines. Decreased
      expression of miR-H4b was directly related to attenuated cell proliferation and
      invasion as well as malfunction of cell cycle in recombinant SHSY5Y cells that
      stably expressing miR-H4b. Bioinformatics analysis and luciferase assays
      demonstrated miR-H4b can directly target p16 mRNA. MiR-H4b exerts its pro
      proliferation function through inhibition of the p16-related PI3K-Akt pathways.
      Our findings provide, for the first time, significant clues regarding the role of
      herpesvirus-encoded miRNAs as a viral modulator to host cells. 

PMID- 26221297
TI  - Berberine reverses abnormal expression of L-type pyruvate kinase by DNA
      demethylation and histone acetylation in the livers of the non-alcoholic fatty
      disease rat.
AB  - Berberine (BBR) can potentially be used as a drug against non-alcoholic fatty
      liver disease (NAFLD) and diabetes. Our previous study found that BBR could
      change the pattern of DNA methylation. But the mechanisms underlying berberine
      are still far from completely understood. In this study, the function of L-PK in
      cell metabolism was explored, and high-fat-diet induced SD rats NAFLD models were
      created. The NAFLD rats were randomly grouped to be oral administration with BBR
      at a dosage of 200 mg/kg daily. Then DNA methylation and histone acetylation
      around the L-type Pyruvate Kinase (L-PK) gene were examined. In the results, we
      found that L-PK had a positive effect on cell proliferation, glucose utilization
      and triglyceride metabolism. However, the expression of L-PK was reduced in the
      livers of NAFLD rats, in accord with the decrease of DNA hypermethylation and
      histone deacetylation in the regulatory regions of L-PK. Notably, BBR treatment
      can restore the expression of L-PK by the demethylation of L-PK promoter and the
      increase in acetylation levels of histone H3 and H4 around L-PK, which indicated
      that BBR may be a potential drug for epigenetic-included diseases. 

PMID- 26221298
TI  - Is there a role for DWI in the diagnosis of sacroiliitis based on ASAS criteria?
AB  - PURPOSE: Sacroiliitis based on MRI is one of the main diagnostic criteria of
      axial spondyloarthritis (SpA). Our purpose was to assess (a) whether apparent
      diffusion coefficient (ADC) values on diffusion-weighted imaging (DWI) differ
      between regions of bone marrow edema (BME) and subchondral normal-appearing bone
      marrow (NABM) in active sacroiliitis, (b) whether ADC values can differentiate
      early SpA and chronic SpA, both in the active and inactive phase, and (c) whether
      ADC values are related to laboratory findings. MATERIALS AND METHODS: 47 patients
      (24 female, 23 male, mean age: 38.53 years) with the diagnosis of SpA were
      included in this retrospective study. 20 age- and sex-matched subjects without
      SpA constituted the control group. ADC measurements were taken from all lesions
      and NABM of each sacroiliac joint. RESULTS: A total number of 120 subchondral BME
      lesions (acute: 17, chronic active: 103) were noted. The mean ADC values of the
      BME lesions (1.30 +/- 0.18 * 10(-3) mm(2)/s) were significantly higher than the
      ADC values in the NABM regions (0.55 +/- 0.08 * 10(-3) mm(2)/s) as well as in
      both the control group (0.56 +/- 0.05 * 10(-3) mm(2)/s) and the chronic inactive
      group (0.54 +/- 0.03 * 10(-3) mm(2)/s). There were more BME regions in patients
      with chronic active sacroiliitis than early SpA patients. Correlation was found
      between the CRP values and ADC values. CONCLUSION: DWI with ADC values may be
      complementary to FS T2-weighted or STIR MR images for accurately diagnosing
      inflammatory sacroiliitis. The value of DWI versus dynamic contrast-enhanced
      imaging in the follow-up needs to be clarified.

PMID- 26221299
TI  - Effects of rosuvastatin on atrial nerve sprouting and electrical remodeling in
      rabbits with myocardial infarction.
AB  - OBJECTIVE: This study is to investigate the effect of rosuvastatin on atrial
      nerve sprouting and electrical remodeling after myocardial infarction (MI).
      METHODS: Rabbit MI model was established by anterior descending branch ligation.
      These models were divided into the sham (n = 9), MI model (n = 7), and
      rosuvastatin intervention (n = 8) groups. Immunohistochemistry was used to detect
      the autonomic atrial nerve distribution. Real-time PCR and Western blot analysis
      were performed to evaluate the mRNA and protein expression levels, respectively.
      RESULTS: Our results from immunohistochemistry showed that, compared with the
      sham group, the densities of tyrosine hydroxylase (TH)- and choline
      acetyltransferase (CHAT)-positive nerve fibers were significantly elevated in the
      MI model group. However, TH- and CHAT-positive nerve fibers were significantly
      decreased by rosuvastatin treatment, suggesting that rosuvastatin could reduce
      autonomic nerve sprouting in acute MI. Moreover, rosuvastatin decreased the mRNA
      and protein expression levels of TH in atrial tissues following MI. Compared with
      the sham group, the mRNA expression level of KCND3 was significantly down
      regulated in the MI model group. And, this down-regulation was restored by
      rosuvastatin treatment. These results suggested that rosuvastatin could inhibit
      the electrical remodeling in atrium after acute MI. CONCLUSION: Atrial nerve
      sprouting and electrical remodeling occur following MI, which could be suppressed
      by rosuvastatin treatment. Our findings provide insights into the understanding
      of the mechanism through which statins decrease the risk of atrium arrhythmia
      after MI.

PMID- 26221300
TI  - (18)F-FDG avid volumes on pre-radiotherapy FDG PET as boost target delineation in
      non-small cell lung cancer.
AB  - BACKGROUND: To investigate whether during/post-radiotherapy FDG uptake locations
      within tumors is likely identified using a pre-radiotherapy scan for non-small
      cell lung cancer (NSCLC), ultimately enabling confirm that a suitable
      metabolically active sub-volume pre-radiotherapy of the primary tumor for
      radiation boosting target. METHODS: Patients with a pathologically proven
      inoperable stage II-III NSCLC were enrolled. For each patient, one pre
      radiotherapy (pre-RT) plus one following 40Gy during-radiotherapy (during-RT) or
      post-radiotherapy (post-RT) FDG PET/CT scans were available. On pre-RT scan, the
      high FDG uptake region were auto-delineated using several percentage of the
      maximal standardized uptake value (SUVmax) thresholds, varying from 40% to 70%.
      On during-RT scan, FDG uptake region is delineated by 40% SUVmax, manual method
      respectively. With the FDG-positive areas on post-RT images is defined as 80%
      SUVmax. The overlap fractions (OFs) were calculated between pre-RT scan and
      during-RT or post-RT scan. Semi-quantitative assessment was used to determine
      SUVmax and metabolic tumor volume (MTV). The SUVmax changes during-RT
      representing the radiotherapy (RT) early metabolic response is attainable. Then,
      a spearman correlation was used to analysis the correlation between percentage
      changes in SUVmax during-RT and SUVmax-threshold definition volume pre-RT.
      RESULTS: Of those 7 patients, a total of 16 FDG-PET scans were acquired. 5
      patients were received pre-RT and during-RT scan, while 2 of these 5 patients
      underwent both post-RT scan. 2 patients were received FDG-PET/CT scan pre-RT and
      post-RT. The pre-RT scan threshold delineations of 50% SUVmax had a large OF with
      the 40% SUVmax threshold and manual method delineation on the during-RT scan,
      74.3% and 84.4%, respectively. Comparably, the 80% SUVmax on the post-RT scan
      also largely corresponded (OF > 72%) with the 50% SUVmax threshold and the volume
      was small compared to the gross tumor volume (GTV), accounting for 29.4%.
      However, the 50% SUVmax threshold was not correlate with the percentage change in
      SUVmax (P > 0.05). CONCLUSIONS: A pre-RT FDG-PET scan allows for the
      identification of during- and post-RT FDG uptake locations. The volume defined by
      50% SUVmax may be a suitable threshold for dose escalation.

PMID- 26221301
TI  - Effect of lipiodol and methylene blue on the thoracoscopic preoperative
      positioning.
AB  - The aim of this study was to compare and analyze the site-specific accuracy of
      mixture of lipiodol and methylene blue (MLM) (0.6 ml, 1:5) and pure methylene
      blue (0.5 ml) on the rabbit lungs. In this study, CT-guided percutaneous
      injection of MLM and methylene blue. Compare the staining degree by biopsy of
      lung tissue. Use 4 points system to evaluate the site-specific accuracy at 6h and
      24 h after injection. For MLM, evaluate its radiopacity by radiation. When
      evaluate the positioning, 2 points mean acceptable, 3 points mean excellent. The
      results indicated that the staining range of MLM is obvious less than that of
      methylene blue (0.6 vs. 1.0 cm, P<0.01), but the staining capacity of MLM is
      higher than that of methylene blue (2.8 vs. 2.2, P = 0.01). About the staining
      abilities which are evaluated as excellent, MLM group accounts for 81%, methylene
      blue group accounts for 38% (P = 0.011). About the radiopacity which are
      evaluated as acceptable or excellent, MLM group accounts for 62%. With good
      direct vision, the suitable positioning rate of MLM can be 100%, which is better
      than that of methylene blue. In conclusion, percutaneous injection of MLM can be
      used to lung positioning. The result shows that use MLM is better than only using
      methylene blue. But it is necessary to do the investigation in human beings in
      order to confirm the feasibility of its clinical application.

PMID- 26221302
TI  - Comparison of biomarkers in rat renal ischemia-reperfusion injury.
AB  - To observe the expressions of monocyte chemoattractant protein -l (MCP-l), kidney
      injury molecule -l (KIM-l) and cystatin C (Cys C) in different periods of rat
      ischemic acute kidney injury (iAKI). The rat renal ischemia-reperfusion injury
      (IRI) model was prepared, including the sham-operation (Sham) group and the I/R
      group. The specimens were collected at different time points after iAKI. The
      expressions of MCP-1, KIM-1 and Cys C of the I/R group were increased earlier
      than Scr and Urea (I/R group vs. Sham group; P < 0.01). The serum MCP-1 of the
      I/R group was earliest increased (MCP-1 vs. KIM-1, Cys C and Scr, P < 0.01).
      Followed by KIM-1 and Cys C; and in the urine samples, the KIM-1 expression was
      the most sensitive (KIM-1 vs. MCP-1, Cys C and Scr, P < 0.01). The
      immunohistochemical results showed the kidney of the Sham group almost had no
      expression, while that of the I/R group significantly expressed MCP-1, KIM-1 and
      Cys C (I/R group vs. Sham group; P < 0.01). MCP-1, KIM-1 and Cys C had important
      predictive values towards AKI, and MCP-1 and KIM-1 were superior to Cys C.
      Different biomarkers had different sensitivities: MCP-1 was earliest increased in
      serum while lasted shortly, KIM-1 was earliest increased in urine and kept
      increasing, thus the detection of urinary KIM-1 might be much more suitable in
      clinics. 

PMID- 26221303
TI  - ABCB1 polymorphism and susceptibility to acute lymphoblastic leukemia: a meta
      analysis.
AB  - BACKGROUND: A large body of studies has investigated the potential role of ABCB1
      polymorphism in ALL susceptibility. However, the results are conflicting. The aim
      of the present meta-analysis was to define the effect of ABCB1 polymorphism on
      ALL risk. METHODS: We identified 8 eligible studies involving 1,308 cases and
      1,427 controls through searching PubMed and Enbase databases. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were used to access the strength of the
      association with both fixed effects and random effect models. RESULTS: We found
      ABCB1 polymorphism was associated with an increased risk of ALL under the
      homozygote genotypes (TT vs. CC: OR, 1.29, 95% CI, 1.08-1.54), the recessive
      model (TT vs. CT + CC: OR, 1.47, 95% CI, 1.02-2.13) and the allele model (T vs.
      C: OR, 1.14, 95% CI, 1.04-1.25). Similar results were indicated in Asian
      populations (TT vs. CC: OR, 1.79, 95% CI, 1.32-2.43; TT vs. CT + CC: OR, 2.55,
      95% CI, 1.47-4.43; T vs. C: OR, 1.38, 95% CI, 1.18-1.62), but not in Caucasian
      populations. CONCLUSIONS: These findings indicate that ABCB1 polymorphism may
      play a critical role in the development of ALL in Asians.

PMID- 26221304
TI  - Relationship between gene mutations and protein expressions of PDGFR alpha and C
      kit in gastrointestinal stromal tumors.
AB  - OBJECTIVE: To investigate the relationship between gene mutations and protein
      expressions of PDGFR alpha and C-kit in gastrointestinal stromal tumors (GIST)
      and its significance in tumorigenesis. METHODS: Single strand conformation
      polymorphism-polymerase chain reaction (PCR-SSCP), immunohistochemistry and
      Western blot were used to detect the gene mutations in PDGFR alpha and C-kit and
      their protein expressions in 105 cases of GIST specimens. RESULTS: In 105 cases
      of GIST, PDGFR alpha gene mutation was found in 12 cases (11.4%), which was
      common in the stomach- derived spindle cell GIST. C-kit gene mutation was found
      in 58 cases (55.2%), which was common in the small intestine. Mutations of PDGFR
      alpha is in 12 cases of GIST were stronger than the C-kit mutations in GIST,
      normal gastrointestinal tissues and schwannomas. No significant correlation was
      found between mutations and C-kit protein expression (P>0.05), while the protein
      expression of PDGFR alpha was significantly correlated with mutations (P<0.0001).
      CONCLUSION: Mutations of PDGFR alpha and C-kit plays an important role in part of
      GIST tumorigenesis. Mutation sites were related with original sites and
      histological types. Most protein expressions were closely related to their gene
      mutations in GIST.

PMID- 26221305
TI  - Effects of quercetin on intracavernous pressure and expression of nitrogen
      synthase isoforms in arterial erectile dysfunction rat model.
AB  - OBJECT: Oxidative stress involved in the regulation of arterial erectile
      dysfunction (A-ED). Previously report have indicated that quercetin have an
      antioxidant effect. In the current study, we have established the rats' model for
      study the therapeutic effect of quercetin on A-ED and further investigated the
      molecular mechanism of action. METHODS: Wistar rats were divided into sham group,
      A-ED group, A-ED group with low dose of quercetin, and A-ED group with high dose
      of quercetin. Intracavernous pressure (ICP) and mean arterial pressure (MBp) are
      two important indicators used for evaluation the A-ED. The changes of ICP and MBp
      were determined by cavernous nerve electrostimulation after treatment of
      quercetin at indicated doses. The expression of nitric oxide synthase (NOS)
      subtypes was detected by RT-PCR and Western blotting. RESULTS: Our results
      indicated that ICP was significantly reduced in A-ED rats model compared with
      sham group, and was significantly increased after quercetin treatment (P < 0.01),
      while no significant effect on the MBp. The data also showed that sGC inhibitor
      ODQ and NOS inhibitor LNNA can significantly inhibited the ICP which induced by
      quercetin. These results suggest that NO-cGMP signaling pathway plays a crucial
      role in A-ED. Then, we found that the mRNA and protein levels of eNOS were
      significantly reduced in A-ED group compared with sham group. After treated with
      quercetin may cause the eNOS RNA and protein were significantly up-regulated (P <
      0.01), showing a dose-dependent effect. iNOS expression have a certain degree of
      increased after quercetin treatment. nNOS expression was not significantly
      increased before and after treated with quercetin. In a word, quercetin can
      improved the A-ED by up-regulated ICP, which related to up-regulation of NO-cGMP
      signaling pathway. CONCLUSION: Preliminary results of this study suggested that
      quercetin protected expression and function of eNOS in cavernous endothelial
      cells, and restored part of normal function of NO-cGMP pathway in the process of
      penis erection.

PMID- 26221306
TI  - Modified glasgow prognostic score predicting high conversion ratio in opioid
      switching from oral oxycodone to transdermal fentanyl in patients with cancer
      pain.
AB  - The aim of this study was to identify predictive factors for higher conversion
      ratio in opioid switching from oral oxycodone to transdermal fentanyl (TDF) in
      patients with cancer pain. The participants of this study were 156 hospitalized
      cancer patients who underwent opioid switching from oral oxycodone to TDF at the
      Affiliated Hospital of Binzhou Medical University between January 1st, 2010 and
      March 31st, 2014. Patient characteristics, modified Glasgow Prognostic Score
      (mGPS), daily oxycodone dose, and reasons for opioid switching were
      retrospectively collected. The effect of variables on the conversion ratio was
      analyzed by multiple regression analysis to identify the predictive factors for
      higher conversion ratio in opioid switching from oral oxycodone to TDF. The
      results showed that the mGPS (odds ratio [OR], 2.358; 95% CI 1.379-4.031; P =
      0.002), the reason for opioid switching (OR, 0.497; 95% CI, 0.298-0.828; P =
      0.007) and equivalent oral morphine dose (OR, 1.700; 95% CI, 1.008-2.867; P =
      0.046) were found to be significant predictors requiring higher conversion ratio
      in opioid switching. This study indicates that higher mGPS, poor pain control
      before switching and higher equivalent oral morphine dose are significant
      predictors of a need for higher conversion ratio in opioid switching from oral
      oxycodone to TDF. These results could contribute to the establishment of evidence
      based medicine in cancer pain relief. 

PMID- 26221307
TI  - Effect of Second mitochondria-derived activator of caspase in combination with
      Docetaxel on lung cancer cell A549.
AB  - This study was to investigate inhibiting effect of structurally unique Second
      mitochondria-derived activator of caspase (Smac) in combination with Docetaxel on
      lung cancer cell line A549. Results showed that the expression of Smac in
      transfected A549 cells was higher than the control cells both at mRNA level and
      protein level (P<0.05). Smac over-expression induced a little apoptosis, however,
      when treated with Docetaxel together, the cells showed a higher apoptosis rate.
      The apoptosis rate was significantly increased in Smac + Docetaxel group when
      compared with that in Smac group and Docetaxel group (P<0.05). Cells cloning
      ability in Smac + Docetaxel group was worse than that of other groups (P<0.05),
      cell mass formed in relatively small quantities and sparse location. Thus, over
      expression of Smac increases the sensitivity of lung cancer A549 cells to
      Docetaxel treatment, and transfection of Smac to tumor cells might provide a
      potential therapy modality. 

PMID- 26221308
TI  - Three hydrogen-rich solutions protect against intestinal injury in uncontrolled
      hemorrhagic shock.
AB  - Intestinal tissue got largely decreased blood supply in uncontrolled hemorrhagic
      shock, because of limited blood mainly supporting brain, heart, kidney etc. This
      makes intestine as the primary injury target after uncontrolled hemorrhagic
      shock. However, limited studies focus on how to protect intestine against
      hemorrhagic shock. Ringer's solution, pentoxifylline and hypertonic saline are
      widely used to resuscitate in haemorrhagic shock and sepsis tissue injury.
      Evidence showed that hydrogen inhibited inflammation and reduced oxidative
      damage. Here we tested the hypothesis whether hydrogen rich Ringer's,
      pentoxifyline and hypertonic saline solutions increase the benefit in protecting
      small intestine from injury in uncontrolled hemorrhagic shock rat model. We
      tested the anti-inflammation effect of H-Ringer's, HHES and HHSH administration.
      We found hydrogen-rich solutions treatment groups showed the decreased MDA, MPO,
      IL-6 and TNF-alpha levels, and increased SOD, IL-10 comparing with those of non
      hydrogen solutions administration groups. Our histological results showed that
      these three solutions with saturation hydrogen alleviatived the intestinal injury
      including the intact intestinal villi and less neutrephil infiltration. Our
      results indicate that these three hydrogen-rich solutions can protect intestinal
      injure after uncontrolled hemorrhagic shock. The protective effect might be
      through inhibiting proinflammatory factors, promoting anti-inflammatory cytokines
      and reducing inflammatory cells infiltration. Our study has potential clinical
      importance of uncontrolled hemorrhagic shock patient's resuscitation. 

PMID- 26221309
TI  - Endovascular management of ruptured basilar superior cerebellar artery junction
      aneurysms: a series of three cases with review of literature.
AB  - Aneurysms located on the bailar superior cerebellar artery (SCA) junction are
      very rare. Endovascular coiling is a safe and feasible treatment option for these
      challenging cases regardless of the narrow operative field, their intimate
      relationship to perforating vessels and cranial nerves, which results in high
      morbidity and mortality rates during clipping. From Jan. 2013 to Jan. 2014, we
      treated three patients (three women between the ages of 44 to 52 years) with
      ruptured basilar SCA junction aneurysms by endovascular embolization. All the
      three patients presented with rupture symptoms and were treated in the acute
      period. Informed and written high-risk consent was given by all patients prior to
      the treatment. Successful angiographic and clinical outcome was achieved in all
      three patients. Endovascular treatment of basilar SCA junction aneurysms with
      coils or combined with stent is an effective and safe option in the management of
      this rare aneurysm. 

PMID- 26221310
TI  - MR imaging analysis of posterior pituitary in patients with pituitary adenoma.
AB  - OBJECTIVE: This study is to investigate posterior pituitary bright spot (PPBS)
      occurrence, distribution and its influencing factors by analyzing MRI-T1WI images
      in patients with pituitary adenoma (PA). METHODS: A total of 123 cases of PA
      patients were enrolled in this study. PPBS occurrence, distribution and MR signal
      characteristics were studied. The relationship of PPBS with PA morphology, tumor
      size, tumor height and immunohistochemical types were explored. RESULTS: Among
      the 123 case of PA patients enrolled in the study, 98 cases were PPBS (+) and 25
      cases were PPBS (-). According to tumor morphology, PA was divided into hourglass
      type (43 cases), barrel type (63 cases) and wedge type (17 cases). Occurrence
      rate of PPBS (+) in barrel type was less than those in hourglass and wedge types
      (P < 0.05). Tumor volume and height in PPBS (+) group were less than these in
      PPBS (-) group (P < 0.05). PPBS signal size in wedge and barrel types were larger
      than that of hourglass type (P < 0.05). CONCLUSIONS: Sagittal MRI-T1WI images
      could well show posterior pituitary and PPBS (+) was related to tumor morphology,
      volume and height but had nothing to do with immunohistochemical types.

PMID- 26221311
TI  - Influence of mechanical stimulation on human dermal fibroblasts derived from
      different body sites.
AB  - Mechanical stimulation is highly associated with pathogenesis of human
      hypertrophic scar. Although much work has focused on the influence of mechanical
      stress on fibroblast populations from various tissues and organs in the human
      body, their effects on cultured dermal fibroblasts by the area of the body have
      not been as well studied. In this study, cultures of skin fibroblasts from two
      different body sites were subjected to cyclic mechanical stimulation with a 10%
      stretching amplitude at a frequency of 0.1 Hz for 24, 36 and 48 hours,
      respectively, and thereafter harvested for experimental assays. Fibroblasts from
      scapular upper back skin, subjected to mechanical loads for 36 and 48 hours,
      respectively, were observed to proliferate at a higher rate and reach confluent
      more rapidly during in vitro culturing, had higher expression levels of mRNA and
      protein production of integrin beta1, p130Cas and TGF beta1 versus those from
      medial side of upper arm. These data indicate that skin fibroblasts, with regard
      to originated body sites studied in the experiments, display a diversity of
      mechanotransduction properties and biochemical reactions in response to applied
      mechanical stress, which contributes to the increased susceptibility to
      hypertrophic scars formation at certain areas of human body characterized by
      higher skin and muscle tension. 

PMID- 26221313
TI  - Peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism decrease
      the risk of diabetic nephropathy in type 2 diabetes: a meta analysis.
AB  - BACKGROUND: The association between peroxisome proliferators-activated receptor
      gamma (PPARgamma) Pro12Ala polymorphism and T2DN risk is inconclusive and
      contradictory. Therefore, we performed a meta-analysis. METHODS: All relevant
      studies were searched by using the PubMed and EMBASE. Odds ratios (ORs) and
      corresponding 95% confidence intervals (CIs) were calculated. Effect model
      selection was on the basis of heterogeneity test. RESULTS: A total of 20 case
      control studies with 9357 subjects were included in this meta-analysis. We found
      that PPARgamma Pro12Ala polymorphism significantly associated with decreased T2DN
      risk (OR = 0.74; 95% CI 0.59-0.94; P = 0.01). In the subgroup analysis by race,
      Caucasian with PPARgamma Pro12Ala polymorphism showed decreased T2DN risk (OR =
      0.63; 95% CI 0.46-0.88; P = 0.006). But Asian with PPARgamma Pro12Ala
      polymorphism did not show decreased T2DN risk (OR = 0.87; 95% CI 0.62-1.22; P =
      0.41). CONCLUSIONS: In conclusion, our meta-analysis study confirmed that
      PPARgamma Pro12Ala polymorphism might contribute to the risk for T2DN.

PMID- 26221312
TI  - Long noncoding RNA MALAT1 as a putative biomarker of lymph node metastasis: a
      meta-analysis.
AB  - Recent studies in cancer have demonstrated that cancerous tissues have a
      significantly higher MALAT1 level than in noncancerous tissues. Overexpression of
      MALAT1 is associated with susceptibility to lymph node metastasis. This meta
      analysis collected all relevant articles and explored the association of MALAT1
      expression levels with lymph node metastasis in patients with carcinoma.
      Literature collections were conducted by searching electronic databases PubMed,
      Cochrane Library, Web of Science (up to January 20, 2015). The odds ratio (OR)
      and its corresponding 95% confidence interval (CI) were calculated to assess the
      strength of the association by using RevMan5.1 software. A total of 573 patients
      from 5 studies were included in this meta-analysis. The results showed lymph node
      metastasis occurred more frequently in patients with high MALAT1 expression group
      than in patients with low MALAT1 expression group (OR = 2.64, 95% CI 1.06-6.56, P
      = 0.04 random-effects model). This meta-analysis demonstrated that overexpression
      of MALAT1 is significantly associated with lymph node metastasis in carcinoma
      patients. 

PMID- 26221314
TI  - GSTM1 null genotype is a risk factor for laryngeal cancer.
AB  - It remains unclear whether the Glutathione S-transferase M1 (GSTM1) null genotype
      influence laryngeal cancer development. This study aimed to investigate the
      interactions among GSTM1 genotype with regard to laryngeal cancer development. We
      searched online electronic databases (PubMed, EMBASE and CNKI). The strength of
      association between the GSTM1 genotype and laryngeal cancer risk was assessed by
      calculating OR with 95% CI. Finally, a total of 25 case-control studies with 2999
      cases and 4942 controls on the association between GSTM1 genotype and laryngeal
      cancer risk were included in this meta-analysis. The overall result showed that
      the GSTM1 null genotype was related to an increased risk of laryngeal cancer (OR
      = 1.34; 95% CI, 1.09-1.63). Subgroup analysis was performed according to
      ethnicity. The results showed that Asians had an increased risk of laryngeal
      cancer (OR = 1.90; 95% CI, 1.40-2.57), while no significant increased risk was
      observed in Caucasians (OR = 1.15; 95% CI, 0.97-1.36). In conclusion, this meta
      analysis suggested that GSTM1 null genotype was significantly associated with
      increased laryngeal cancer risk. 

PMID- 26221315
TI  - Effect of heat shock pretreatment on apoptosis and metallothionein expression in
      rat cardiomyocytes.
AB  - To investigate the effect of heat shock pretreatment on apoptosis and
      mitochondrial metallothionein (MT) expression in rat cardiomyocytes. In vitro
      cultured H9C2 cells were randomly divided into three groups: control, hydrogen
      peroxide (H2O2) injury, and H2O2 injury after heat shock pretreatment (n = 6 per
      group). Cardiomyocyte apoptosis and caspase-3 activity were assayed after
      treatment. Mitochondrial cytochrome (cyt) c and MT expression was assayed by
      Western blotting. Compared with the control group, the H2O2 injury group had a
      growing number of apoptotic cardiomyocytes (P < 0.01) and significantly elevated
      caspase-3 activity (P < 0.01) with markedly increased mitochondrial cyt c and MT
      expression (P < 0.01). After heat shock pretreatment, the numbers of apoptotic
      and necrotic cardiomyocytes (P < 0.01) and the caspase-3 activity significantly
      declined (P < 0.01), while mitochondrial cyt c and MT expression continued to
      increase (P < 0.01) compared with the H2O2 injury group. Heat shock pretreatment
      inhibits cardiomyocyte apoptosis, which may have a protective effect on
      cardiomyocytes by increasing the expression of myocardial protective MT and
      reducing the release of mitochondrial cyt c. 

PMID- 26221316
TI  - Association between nonalcoholic fatty liver disease and carotid atherosclerosis:
      a meta-analysis.
AB  - OBJECTIVE: We carried out a meta-analysis about non-alcoholic fatty liver
      disease, carotid artery intima-media thickness and carotid artery plaque to
      explore the association between nonalcoholic fatty liver disease (NAFLD) and
      carotid atherosclerosis. METHODS: We searched for case-control studies about the
      relationship between NAFLD and carotid intima-media thick (IMT) published from
      2004 to 2014 according to inclusion and exclusion criteria and extracted the
      relevant data. Statistical analysis was processed by RevMan 5.2 software.
      RESULTS: 9 studies were involved totally, including 2446 subjects (925 patients
      and 1521 controls). We found that there was a significant heterogeneity between
      NAFLD and carotid IMT. By the random effects model we calculated and combined the
      mean value of carotid IMT. The mean difference was 0.16 mm with 95% confidence
      interval (0.11, 0.21). Studies showed that there was also heterogeneity between
      carotid artery plaque and NAFLD. By the random effects model the calculated and
      combined OR value was 3.73 with 95% confidence interval (2.42, 5.74). The
      publication bias of the included studies did not exist. CONCLUSION: The IMT in
      NAFLD patients increased 0.16 mm compared with the control group, and risk of
      carotid plaque was 3.73 times than that of the controls. It is necessary for
      NAFLD patients to carry out routine carotid ultrasound detection to predict the
      occurrence of carotid atherosclerosis and assess the risk of cardiovascular
      disease.

PMID- 26221317
TI  - Anthrax toxin receptor 2 gene (ANTXR2) rs4333130 is associated with ankylosing
      spondylitis.
AB  - Results of recent published studies on the association between the ANTXR2
      rs4333130 polymorphism and the risk of ankylosing spondylitis (AS) have often
      been conflicting. To make a more precise estimation of the potential
      relationship, a meta-analysis was performed. We conducted a comprehensive search
      in the electronic database of PubMed and Embase to retrieve relevant articles.
      Nine studies including 14,523 cases and 34,421 controls were finally selected in
      this meta-analysis. ANTXR2 rs4333130 was significantly associated with a
      decreased risk of AS (OR=0.87; 95% CI, 0.84-0.90; P<0.00001). In the subgroup
      analysis by race, ANTXR2 rs4333130 was significantly associated with a decreased
      risk of AS in both Asian (OR=0.80; 95% CI, 0.65-0.99; P=0.04) and Caucasian
      (OR=0.87; 95% CI, 0.84-0.90; P<0.00001). In the subgroup analysis by HLA-B27
      status, HLA-B27 positive individuals with ANTXR2 rs4333130 showed decreased AS
      risk (OR=0.89; 95% CI, 0.83-0.96; P=0.002). However, HLA-B27 negative individuals
      with this polymorphism did not showed decreased AS risk (OR=0.96; 95% CI, 0.88
      1.06; P=0.44). In conclusion, this meta-analysis suggested a significant
      association between ANTXR2 rs4333130 polymorphism and AS risk. 

PMID- 26221318
TI  - (R)-3-oxobutyl 3-hydroxybutanoate (OBHB) induces hyperketonemiain Alzheimer's
      disease.
AB  - The present study demonstrates the effect of (R)-3-oxobutyl 3-hydroxybutanoate
      (OBHB) on hyperketonemia in 2 patients with Alzheimer's disease dementia who were
      performed a mini-mental state examination score of above 11 and 10. The patients
      were treated with OBHB for 24 months and received usual diet. The patients were
      administered 15 g of OBHB three times per day for two days. The dosage of OBHB
      was increased to 30 g three times daily from the day 4. OBHB was always taken
      after adding with soda-flavoured syrups in order to mask the bitter taste. The
      measurement of plasma beta-hydroxybutyrate (betaHB) levels after every week was
      performed to determine OBHB plasma betaHB dose-response relationships. Precision
      Xtra Glucose and Ketone Monitoring System (Abbott Diabetes Care, Inc., Alameda,
      CA, USA) was used to measure betaHB levels in the blood samples. We did not
      observe any adverse effects of OBHB in any of the patients and it was well
      tolerated throughout the 24 months treatment period. Both of the patients showed
      marked improvement in mood, behaviour, self-care, cognitive and daily activity
      performance. The results revealed a marked improvement in conversation and
      interaction after administration of OBHB doses. The biochemical investigation of
      the blood samples before, during OBHB treatment and after 24 months of the
      treatment revealed only minor changes in the plasma lipids. There was a decrease
      in cholesterol level from 251 to 158 and 247 to 152 mg/dL in the two patients
      respectively after 24 months of the treatment. Similarly the level of high
      density lipoprotein cholesterol was found to decrease from 157 to 79 and 149 to
      76 mg/dL, respectively in two patients. Thus OBHB can be a promising agent in the
      treatment of hyperketonemia and can be taken as an oral supplement without
      changing the habitual diet. 

PMID- 26221319
TI  - Garlic and alpha lipoic supplementation enhance the immune system of albino rats
      and alleviate implications of pesticides mixtures.
AB  - This study aimed to investigate age dependent immune-system response versus
      exposure to different doses of mixture of (chlorpyrifos, profenofose, and
      fenitrothion) and/or combined with 60 and 250 mg kg(-1) alpha lipoic acid and
      garlic, respectively. 120 males of albino rats were divided to two groups
      according to age; weaning group (2 months age and 60-80 gm.), adult (6 months and
      180-200 gm). Each age was divided into 6 subgroups treated orally for 3 months ,
      G1 (control), G2 high dose (HDPM) CPF10 mg kg(-1), PRO 3 mg kg(-1), FEN 6 mg kg(
      1), G3 low dose (LDPM) CPF 1 mg kg(-1), PFN 0.3 mg kg(-1) and FEN 0.6 mg kg(-1),
      G4 AOX (alpha lipoic + Garlic), G5 HDPM + AOX and G6 LDPM + AOX. Results showed
      significant inhibition in serum acetylcholinesterase (AChE), elevation in
      malondialdehyde (MDA) concurrent with reduction in total reduced glutathione
      (GSH) in both ages was recorded as well as, decrease in IGG, IGM, Lymphocyte
      transformation and Phagocytosis humeral and cellular immunity confirmed by
      alteration in lymph nodes architecture. This study was concluded that the
      supplementation with alpha lipoic acid and garlic improved previous alternations
      slightly to be more or less near the control level in both adult and weaning
      rats. It seems that, immune-responses of both adult and weaning rats were
      slightly similar. 

PMID- 26221320
TI  - Recent progress on small vessel disease with cognitive impairment.
AB  - Vascular cognitive impairment (VCI) refers to different degrees of cognitive
      dysfunction syndrome caused by all kinds of cerebral vascular disease and
      vascular factors. Before in the development of vascular dementia (VaD), early
      diagnosis and intervention can prevent and delay the progress of VCI, even
      reverse cognitive impairment. In this review, we summarized the research progress
      of vascular cognitive impairment in pathophysiology, biomarkers and treatments,
      etc. 

PMID- 26221321
TI  - Therapeutic effect and safety of laparoscopic cervical cerclage for treatment of
      cervical insufficiency in first trimester or non-pregnant phase.
AB  - OBJECTIVE: To investigate the therapeutic effect and safety of cerclage placed in
      pregnancy via laparoscopy (CPL) in the first trimesteror in non-pregnant phase
      (CNL). METHODS: A total of 134 cervical insufficiency patients who were treated
      with cervical cerclage were included. All the patients were divided into 3
      groups. CPL group: 43 cases were treated with cerclage placed in pregnancy via
      laparoscopy in the first trimester, of which 26 cases received termination of
      pregnancy. CNL group: 58 cases were treated with cerclage placed via laparoscopy
      in the non-pregnant phase, of whom 34 received termination of pregnancy. TVC
      group: 33 cases received traditional vaginal cerclage placed in second trimester,
      of whom 33 cases received termination of pregnancy. RESULTS: All patients
      received a successful operation without any complications during or after
      surgery. The post-operative hospitalization duration in CPL group was
      significantly shorter than that in TVC group. In 3 groups, for all patients who
      received termination of pregnancy, the postoperative full term delivery rate,
      fetal salvage rate (if pregnancy lasted >= 14 weeks), mean gestational weeks (if
      pregnancy lasted >= 14 wk) after operation, post-operation gestational age for
      all patients, and weeks of pregnancy gained were observed and analyzed. There
      were no significant differences of every index between CPL group and CNL group.
      Every index in TVC group was lower than that in both CNL group and CPL group.
      CONCLUSION: CPL or CNL for treatment of cervical insufficiency is safe and
      effective, with a better therapeutic effect than that of TVC in the second
      trimester.

PMID- 26221322
TI  - ST segment elevation in secondary cardiac cancer: a case report and review of the
      literature.
AB  - Secondary cardiac cancer most frequently originates from primary lung cancer and
      most commonly occurs in the pericardium. On electrocardiographic examination,
      patients with secondary cardiac cancer occasionally show ST segment elevation
      that mimics acute coronary syndrome, despite the absence of coronary artery
      occlusion. We herein describe a rare case of secondary cardiac cancer that
      presented with ST segment elevation and review the literature regarding ST
      segment elevation caused by secondary cardiac cancer. A 73-year-old Japanese
      woman was admitted to the hospital with chest pain. Electrocardiography showed
      abnormal ST segment elevation in the precordial and lateral leads, suggestive of
      ST-elevation myocardial infarction. Emergency coronary angiography showed
      occlusion of the distal left anterior descending coronary artery (LAD), and plain
      old balloon angioplasty of the LAD was performed. The ST segment elevation
      initially resolved after angioplasty, but recurred after 7 days. Contrast
      enhanced chest computed tomography showed primary lung cancer in the left lower
      lobe, pericardial metastasis, and myocardial metastasis in the intraventricular
      septum and posterolateral wall of the left ventricle. Histopathological
      examination of the lung cancer was not performed. Patients with ST segment
      elevation due to secondary cardiac cancer may have symptoms and
      electrocardiographic changes mimicking anteroseptal or lateral infarction without
      the development of abnormal Q waves. These findings are frequently associated
      with posterolateral or anteroseptal invasion by primary lung cancer and may
      indicate a poor prognosis. In conclusion, physicians should be aware that
      secondary cardiac cancer may present with symptoms and ST segment elevation
      mimicking acute coronary syndrome, indicating a poor prognosis. 

PMID- 26221323
TI  - Efficacy of adjuvant chemotherapy combined with immunotherapy with cytokine
      induced killer cells for gastric cancer after d2 gastrectomy.
AB  - BACKGROUND AND AIMS: It remains a challenge to prevent the local recurrence or
      distant metastasis of gastric carcinoma after D2 gastrectomy. Cytokine-induced
      killer (CIK) cells have shown promising activity against solid tumors in vitro
      and in vivo. We investigated the effect of adjuvant chemotherapy combined with
      autologous CIK therapy after D2 gastrectomy compared with adjuvant chemotherapy
      alone after D2 gastrectomy in patients with stage II-III gastric cancer. METHODS:
      From January 2009 to December 2011, 226 patients with stage II-III gastric cancer
      who had had curative D2 gastrectomy were enrolled. Eighty-nine patients (CIK
      group) received adjuvant chemotherapy combining with autologous CIK therapy and
      137 patients (control group) received adjuvant chemotherapy alone. Disease-free
      survival (DFS) and overall survival (OS) were evaluated. RESULTS: Patients in the
      CIK group had longer DFS and OS than patients in the control group (DFS 41.0
      months vs. 32.0 months, OS 45.0 months vs. 44.0 months, by log-rank test P =
      0.006 and P = 0.028, respectively). In subgroup analysis, no significant
      differences in DFS and OS were observed between the two groups for the patients
      with stages II disease. Patients with stage III disease in the CIK group had
      longer median DFS and OS than patients in the control group (P = 0.031 and P =
      0.038, respectively). In multivariate analysis, the stage and the interaction of
      stage and CIK therapy were independent prognostic factors for DFS and OS.
      CONCLUSIONS: The data suggest that adjuvant chemotherapy combined with autologous
      CIK therapy can improve prognosis for gastric carcinoma patients after D2
      gastrectomy, especially for the patients with stage III disease.

PMID- 26221324
TI  - MTHFD1 gene polymorphisms as risk factors involved in orofacial cleft: an
      independent case-control study and a meta-analysis.
AB  - BACKGROUND: Orofacial clefts (OFCs) were among the most familiar birth defects in
      the world, which had been reported to be influenced by the folic acid ingestion
      in pregnancy previously. Methylenetetrahydrofolate dehydrogenase1 (MTHFD1) gene
      was associated with the susceptibility of OFCs through a complex metabolism
      correlate with folic acid. The aim of our study was to evaluate the correlation
      of five single-nucleotide polymorphisms (SNPs) within MTHFD1 related to the OFCs
      risk in a Chinese population. METHODS: By the use of polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP), we genotyped 5 filtered SNPs
      (identified by Haploview 4.2 software with HapMap databases) on MTHFD1 gene:
      118913T>C, 31136A>G, 58893A>G, 1958G>A and 61869T>C of 216 subjects (108 OFCs
      cases and 108 healthy controls) from a Chinese population. The association
      between these SNPs and OFCs risk was investigated by student t-test, one-way
      analysis of variance (ANOVA) and chi-square test with GraphPad Prism 5.0
      software. Furthermore, we also performed a meta-analysis of relevant studies to
      investigate the association between MTHFD1 1958G>A and the susceptibility of
      OFCs. RESULTS: Through the genotyping, the AA genotype was found significantly
      correlated with the susceptibility of OFCs compared with other SNPs on MTHFD1,
      yielding an OR of 2.71 (95% CI = 1.12-6.58, P = 0.025) under the homozygous model
      and an OR of 2.37 (95% CI = 1.06-5.30, P = 0.033) under the recessive model.
      While other selected SNPs 118913T>C and 31136A>G were also associated with an
      increased OFC risk, the results were not statistically significant (all P >
      0.05). However, the overall result of meta-analysis did not support the
      conclusion that the 1958G>A variant could be a genetic susceptible factor for
      OFCs (A allele vs. G allele: OR = 1.02, 95% CI = 0.85-1.23, AA vs. GG: OR = 1.06,
      95% CI = 0.69-1.63, GA vs. GG: OR = 1.02, 95% CI = 0.81-1.27, AA vs. GG+GA: OR =
      0.94, 95% CI = 0.61-1.46, AA+GA vs. GG: OR = 0.94, 95% CI = 0.74-1.19).
      CONCLUSIONS: The MTHFD1 1958G>A variant was significantly associated with the
      increased OFCs risk in Chinese population. However, this association was not
      supported by meta-analysis of all relevant studies. Further investigations about
      functional impact of this polymorphism were needed.

PMID- 26221325
TI  - Comparison of transumbilical single-port laparoscopic cholecystectomy and fourth
      port laparoscopic cholecystectomy.
AB  - This work aims to compare the curative effect of transumbilical single-port
      laparoscopic cholecystectomy (TUSPLC) and four-port laparoscopic cholecystectomy
      (FPLC). 200 patients with cholecystolithiasis were enrolled in this study. They
      were randomly divided into TUSPLC group and FPLC group, 100 cases in each group,
      and the TUSPLC and FPLC was performed, respectively. The surgical time,
      intraoperative complication, conversions rate, postoperative pain, postoperative
      analgesic drug use, incision infection, postoperative hospitalization time and
      postoperative cosmetic results in two groups were compared. The total conversion
      rate, conversion rate with Nassar grade II, and conversion rate with Nassar grade
      III in TUSPLC group were significantly higher than FPLC group (P < 0.01), and the
      incision cosmetic result after 1 month in TUSPLC group was obviously better than
      FPLC group (P < 0.01), but the surgical time in TUSPLC group was significantly
      longer than FPLC group (P < 0.01). There was no significant difference of
      incision infection, intraoperative complication, and postoperative
      hospitalization time, incision pain in postoperative first and second day,
      postoperative use of analgesia drug and incision cosmetic result on discharge day
      between two groups (P > 0.05). TUSPLC has obvious advantage in treatment of
      Nassar grade I patients with cholecystolithiasis. It can be used as a supplement
      for standard laparoscopic gallbladder surgery. It is safe and feasible, without
      abdominal scar, thus achieving to excellent cosmetic result and high satisfaction
      in patients. 

PMID- 26221326
TI  - Transcutaneous electrical acupoint stimulation alleviates the hyperandrogenism of
      polycystic ovarian syndrome rats by regulating the expression of P450arom and
      CTGF in the ovaries.
AB  - The present study was to investigate the effects of transcutaneous electrical
      acupoint stimulation (TEAS) in alleviating the hyperandrogenism of polycystic
      ovarian syndrome (PCOS) model rats induced by testosterone propionate and the
      possible underlying mechanism. Thirty-six female Sprague-Dawley rats were
      randomly divided into normal control, PCOS model and TEAS groups with twelve rats
      in each group. The PCOS model rats were established by single injection of
      testosterone propionate at 9th day after birth, and the status of estrous
      cyclicity for each rat was observed. When the 8-week TEAS treatment completed,
      the weight of body, uterus and ovaries of the rats were respectively measured.
      The serum levels of total testosterone (TT), sex hormone binding globulin (SHBG),
      androstenedione, luteinizing hormone (LH), follicle stimulating hormone (FSH) and
      estradiol (E2) were detected. The mRNA and protein expression levels of aromatase
      cytochrome P450 (P450arom) and connective tissue growth factor (CTGF) in the
      ovaries of the rats were respectively measured with real-time quantitative PCR
      and immunohistochemistry. The TEAS treatment significantly improved the estrous
      cycles of the PCOS rats and the TEAS group displayed significantly lower average
      body and ovaries weights than the PCOS model group (P < 0.05). TEAS significantly
      decreased the serum TT, free androgen index (FAI), androstenedione and LH/FSH
      levels, and increased the serum FSH levels of the PCOS rats (P < 0.05). The TEAS
      treatment significantly increased the P450arom mRNA as well as protein expression
      levels and significantly decreased the CTGF mRNA as well as protein expression
      levels in the ovaries of the PCOS rats (P < 0.05). We concluded that it is
      through regulating the P450arom and CTGF expression levels in the ovaries that
      TEAS significantly alleviates the hyperandrogenism of PCOS rats induced by
      testosterone propionate. 

PMID- 26221327
TI  - Correlation of APOBEC3 in tumor tissues with clinico-pathological features and
      survival from hepatocellular carcinoma after curative hepatectomy.
AB  - OBJECTIVE: This study aimed to evaluate the relationships between members of
      APOBEC3 in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and
      prognosis. METHODS: Using the expression profile GSE36376 from Gene Expression
      Omnibus (GEO), we compared APOBEC3 expression between tumor and non-tumor
      tissues, and correlated this with clinico-pathological features and outcomes of
      HCC patients. RESULTS: A3B, A3D, A3F and A3H were overexpressed in HCC tumor
      tissues compared to non-tumor tissues (all P<=0.001). Cox regression shown that
      A3G was negatively associated with overall survival of HCC patients (HR=2.277,
      95% CI=1.324-3.915, P=0.033), in contrast, A3C level in tumor tissues might play
      a positive role in HCC overall survival (HR=0.364, 95% CI=0.182-0.727, P=0.004).
      Interestingly, A3F contributed to a poor disease-free survival of HCC (HR=3.383,
      95% CI=1.249-9.715, P=0.017), while A3H may be a positive factor associated with
      HCC disease-free survival (HR=0.25, 95% CI=0.098-0.636, P=0.004). Cirrhosis,
      tumor size and intrahepatic metastasis were associated with HCC poor disease-free
      survival (HR=1.838, 95% CI=1.308-2.583, P<0.001; HR= 1.095, 95% CI=1.042-1.15,
      P<0.001 and HR=3.669, 95% CI=2.447-5.5, P<0.001; respectively). Logistic
      regression analysis indicated that up-regulation of A3F in tumor tissues promoted
      HCC vascular invasion, intrahepatic metastasis and AFP elevation (all P<0.05). In
      contrast, A3H might decrease these risks (all P<0.05). CONCLUSIONS: APOBEC3G and
      APOBEC3F might be risk factors for HCC development and survival, while APOBEC3C
      and APOBEC3H should play positive roles in HCC aggressiveness and prognosis.
      Further investigation for APOBEC3 mechanisms are needed in the future.

PMID- 26221328
TI  - Ocular syphilis: an alarming infectious eye disease.
AB  - BACKGROUND: To describe the clinical manifestations and ancillary examination
      outcomes of ocular syphilis in Southeast China. MATERIALS AND METHODS: This is a
      retrospective, nonrandom case study. Demographic information, serum and
      cerebrospinal fluid (CSF) test results, and findings of fundus fluorescein
      angiography (FFA), indocyanine green angiography (ICGA), and spectral domain
      optical coherence tomography (SD-OCT) were analyzed. RESULTS: The study examined
      21 eyes of 13 patients (average age 50.3 +/- 5.9 (range 37-61) years). HIV co
      infection was found in one patient. The most common manifestation was
      chorioretinitis (52.4%). Disc hyperfluorescence (66.7%) and persistent dark spots
      (91.7%) were the most common findings on FFA and ICGA, respectively. The inner
      segment/outer segment junction (IS/OS) loss was the most frequent manifestation
      (86.7%). Among the six patients with confirmed neurosyphilis, the average CSF
      protein level was 528.8 +/- 327.1 mg/L. Visual acuity (VA) was improved in 8 of
      13 eyes (61.5%) after treatment. CONCLUSIONS: The manifestations of ocular
      syphilis can mimic any eye disease. Chorioretinitis was the most common finding
      in this case series. "Leopard spots" was the characteristic manifestation on FFA.
      IS/OS loss was the most common finding in patients with posterior uveitis on SD
      OCT. Lumbar puncture can contribute to the diagnosis of neurosyphilis. Treatment
      for ocular syphilis was effective in these patients.

PMID- 26221329
TI  - Value of intraoperative parathyroid hormone monitoring in papillary thyroid
      cancer surgery: can it be used to guide the choice of operation methods?
AB  - BACKGROUND: To assess the diagnostic value of decreased parathyroid hormone (PTH)
      in hypoparathyroidism after unilateral operation. METHODS: A study was conducted
      on patients with PTC undergoing total or near-total thyroidectomy plus central
      neck dissection (CND). RESULTS: Postoperative hypocalcemia was found in 42
      patients (51.2%). For patients undergoing bilateral CND, those whose tumor
      invasion proceeded beyond the thyroid capsule have a higher rate of postoperative
      hypoparathyroidism (P<0.05). PTH level of hypoparathyroidism patients was lower
      than that of non-hypoparathyroidism patients from surgery to 6 months later
      (P<0.05). When unilateral thyroidectomy and central region dissection were
      completed, PTH level decreased by 47.06% in hypoparathyroidism patients, which
      was significantly higher than non-hypoparathyroidism patients (28.35%) (P<0.001).
      PTH level (AUC 0.806) and its decreasing degree (AUC 0.736) played predicting
      roles in assessing postoperative hypoparathyroidism (P<0.001). CONCLUSIONS: For
      PTC surgery, PTH level and its decreasing degree played predicting roles in
      assessing postoperative hypoparathyroidism.

PMID- 26221330
TI  - Genetic polymorphism in alcohol dehydrogenase 2 (ADH2) gene and alcoholic liver
      cirrhosis risk.
AB  - The alcohol dehydrogenase 2 (ADH2) gene has been implicated in the development of
      alcoholic liver cirrhosis (ALC). However, the results are inconsistent. In this
      study, a meta-analysis was performed to assess the associations between the ADH2
      polymorphism and the risk of ALC. Relevant studies were retrieved by searching
      PubMed, Web of Science, CNKI, Wanfang and VIP databases up to January 10, 2015.
      The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated
      using the fixed- or random effects model. A total of 21 case-control studies
      included 1812 cases and 3468 controls were included. Overall, the ADH2
      polymorphism was associated with a decreased risk of ALC in all four genetic
      models (dominant model: OR=0.56, 95% CI: 0.38-0.83; recessive model: OR=0.59, 95%
      CI: 0.39-0.91; *1/*2 vs. *1/*1: OR=0.58, 95% CI: 0.40-0.85; *2/*2 vs *1/*1:
      OR=0.35, 95% CI: 0.16-0.75). Besides, in stratification analysis by ethnicity,
      similar results were observed in Asian populations, however, we detected no
      association in Caucasian populations under recessive and homozygote comparison
      model. The pooled evidence suggests that ADH2 polymorphism may be an important
      protective factor for alcoholic liver cirrhosis, especially for Asians. 

PMID- 26221332
TI  - Dual-energy CT angiography for the diagnosis of intracranial dural arteriovenous
      fistula.
AB  - PURPOSE: To investigate the clinical utility of dual-source dual-energy CT
      angiography (DSDECTA) for diagnosing intracranial dural arteriovenous fistula
      (DAVF). METHODS: Nine intracranial DAVF patients were examined using Siemens
      DSDECTA and cerebral digital subtraction angiography (DSA). Imaging data were
      retrospectively analyzed to evaluate the concordance between the imaging
      modalities. RESULTS: DSDECTA examination showed that the blood-supplying arteries
      were thickened and the draining veins and dural sinuses were expanded in all 9
      patients. The presence and characteristics of intracranial DAVF were confirmed
      using DSA. Head CT showed subarachnoid hemorrhage in 4 cases and intracerebral
      hematoma in 3 cases. CONCLUSION: Although DSA is the gold standard for DAVF
      diagnosis, DSDECTA is less invasive and more suitable for revealing the three
      dimensional structure of secondary intracranial lesions as well as other DAVF
      characteristics. Thus, DSDECTA may be a new alternative for noninvasive screening
      of suspected DAVF patients before interventional embolization and surgical
      resection.

PMID- 26221331
TI  - Use of concept maps to promote electrocardiogram diagnosis learning in
      undergraduate medical students.
AB  - Concept mapping is an effective method in teaching and learning, however this
      strategy has not been evaluated among electrocardiogram (ECG) diagnosis learning.
      This study explored the use of concept maps to assist ECG study, and sought to
      analyze whether this method could improve undergraduate students' ECG
      interpretation skills. There were 126 undergraduate medical students who were
      randomly selected and assigned to two groups, group A (n = 63) and group B (n =
      63). Group A was taught to use concept maps to learn ECG diagnosis, while group B
      was taught by traditional methods. After the course, all of the students were
      assessed by having an ECG diagnostic test. Quantitative data which comprised test
      score and ECG features completion index was compared by using the unpaired
      Student's t-test between the two groups. Further, a feedback questionnaire on
      concept maps used was also completed by group A, comments were evaluated by a
      five-point Likert scale. The test scores of ECGs interpretation was 7.36 +/- 1.23
      in Group A and 6.12 +/- 1.39 in Group B. A significant advantage (P = 0.018) of
      concept maps was observed in ECG interpretation accuracy. No difference in the
      average ECG features completion index was observed between Group A (66.75 +/-
      15.35%) and Group B (62.93 +/- 13.17%). According qualitative analysis, majority
      of students accepted concept maps as a helpful tool. Difficult to learn at the
      beginning and time consuming are the two problems in using this method,
      nevertheless most of the students indicated to continue using it. Concept maps
      could be a useful pedagogical tool in enhancing undergraduate medical students'
      ECG interpretation skills. Furthermore, students indicated a positive attitude to
      it, and perceived it as a resource for learning. 

PMID- 26221333
TI  - Interleukin-34 in rheumatoid arthritis: potential role in clinical therapy.
AB  - OBJECTIVE: To investigate, whether interleukin (IL)-34 can be used as marker for
      treatment effectiveness in rheumatoid arthritis (RA). METHODS: Serum samples were
      collected from 35 healthy participants and 83 patients with RA before as well as
      4 weeks and 12 weeks after treatment initiation with the tumor necrosis factor
      alpha (TNF-alpha) inhibitor Etanercept. Related clinical data and hand radiograms
      of the patients were evaluated and serum IL-34, IL-6, IL-8, TNF-alpha, matrix
      metalloproteinase-3 (MMP-3) in addition to anti-cyclic citrullinated peptide
      (CCP) antibody concentrations were measured by ELISA. RESULTS: Serum
      concentrations of IL-34, IL-6, IL-8, TNF-alpha, MMP-3 and anti-CCP antibodies
      were markedly elevated in RA patients compared with controls (P<0.001),
      significantly decreased during treatment and correlated with erythrocyte
      sedimentation rate (ESR), C-reactive protein (CRP) and RA disease activity
      (P<0.05). IL-34 correlated withIL-6, IL-8, TNF-alpha, MMP-3 and anti-CCP
      antibodies in RA patients at baseline (P<0.01) and also with IL-8, MMP-3, IL-6,
      and DAS28 changes during therapy. Patients in stage III of hand X-ray RA scores
      had higher IL-34 serum concentrations than in stage II (P<0.05). IL-34 level
      decreased significantly (P<0.01) starting from 4 weeks after therapy initiation.
      CONCLUSIONS: IL-34 serum concentrations correlated with inflammatory cytokines
      before and during therapy and were significantly higher in stage III of hand X
      ray score patients than in stage II participants. IL-34 might be used both as a
      biomarker for RA diagnosis and therapy efficiency.

PMID- 26221334
TI  - Interleukin-2 administration after modified radical mastectomy in breast cancer
      therapy increases peripheral regulatory T cells.
AB  - BACKGROUND: Breast cancer (BC) deaths are a major concern worldwide, and modified
      radical mastectomy (MRM) still represents a primary therapeutic strategy. Post
      surgery administration of interleukin (IL)-2 for BC therapy has been implemented
      in China recently. Although its impact on regulatory T cells (Tregs) has been
      documented in some cancer types, such as melanoma, the IL-2-mediated changes in
      the Treg composition after MRM in BC treatment remain unknown. METHODS: As
      registered with the Chinese Clinical Trial Registry, 34 newly diagnosed BC
      patients, aged 20-65 years, were enrolled in this trial. Patients were randomized
      to the IL-2-treated group (n=15) and the untreated control group (n=19).
      Peripheral blood mononuclear cells were isolated at time points of pre-operation
      (PreOP) and post-operation Day 1 (POD1), POD3, and POD7. Cells were subjected to
      flow cytometric assays to identify CD4(+) CD25(+) Foxp3(+) Tregs, as well as real
      time quantitative polymerase chain reaction analysis of FOXP3 expression.
      RESULTS: We found that the surgery caused a significant decrease in the
      percentage of Tregs on POD1, followed by a significant increase characterized by
      a peak value on POD7 with a more than 18% increase relative to the Pre-OP levels.
      We observed that the Treg percentages in the IL-2-treated group were
      significantly greater than those in the control group on POD3 and POD7, whereas
      no such statistical difference was observed on POD1. The FOXP3 expression
      analysis revealed consistent trends as observed by flow cytometry. CONCLUSIONS:
      Post-operative administration of IL-2 amplifies the surgery-induced augmentation
      of both Tregs and FOXP3 expression in BC therapy.

PMID- 26221335
TI  - Evaluation of uterine artery recanalization and doppler parameters after
      bilateral uterine artery ligation in women with postpartum hemorrhage.
AB  - AIM: The evaluation of the uterine artery recanalization rate and color Doppler
      parameters during follow-up after bilateral uterine artery ligation (BUAL) for
      postpartum hemorrhage (PPH) related to uterine atony. MATERIAL AND METHOD: A
      total of 40 female patients who underwent BUAL for PPH related to uterine atony
      and 96 females who gave birth without complication at Hatay Obstetrics and
      Gynecology Hospital between January 2009 and December 2012 (48 months) were
      included in the study. The patients' uterine artery recanalization rate and all
      subjects' color Doppler ultrasonographic parameters (PI, RI, PSV and EDV) were
      evaluated at the 6th and 12(th) months. RESULT: No statistically significant
      difference was found between the age, obstetric history (gravida and parity),
      BMI, type of delivery, birth weight and gestational age when the demographic data
      of the groups were evaluated. The patient group UtA recanalization rate was 32.5%
      and 37.5% for the left and right UtA respectively at the 12-month follow-up. No
      statistically significant difference was found in the comparison of 6- and 12
      month right and left uterine artery diameters and color doppler parameters of the
      patient group (UtA diameters P=0.322 and P=0.787, RI index P=0.390 and P=0.094,
      PI index P=0.949 and P=0.374, PSV P=0.335 and P=0.085, EDV P=0.173 and P=0.418,
      respectively). However, right and left ovarian volume was found to significantly
      increase during follow-up in patient group (P<0.001 for both right and left
      ovary). On the other hand, a statistically significant difference was found
      between the patient group and the control group in the comparison of the 6- and
      12-month right and left uterine artery values (6th month; P<0.001 for both UtA
      diameters, RI, PI, PSV, EDV; 12(th) month; P<0.001 for right UtA diameter, RI,
      PI, PSV, EDV and P=0.002 for left UtA diameter). A statistically significant
      difference was found only in right ovary volume in the 6th month evaluation of
      the patient and control group ovary volumes (P=0.011). DISCUSSION: The
      recanalization rate and isolated uterine blood supply during low-term follow-up
      are low following the BUAL technique. The evaluation of future fertility results
      will be helpful in determining the reliability of this procedure in a definite
      manner.

PMID- 26221336
TI  - An special epithelial staining agents: folic acid receptor-mediated diagnosis
      (FRD) effectively and conveniently screen patients with cervical cancer.
AB  - High-quality screening with cytology has markedly reduced mortality from cervical
      cancer. However, it needs experienced pathologists to review and make the final
      decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to
      effectively and conveniently screen patients with cervical cancer. We conduct
      present study aim to assess clinical significances of FRD in screening cervical
      cancer. A total of 169 patients were enrolled at Chinese People's liberation Army
      (PLA) general hospital. We compared diagnostic significances of FRD with thinprep
      cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any
      lesion suspicious for cervical cancer. The sensitivity and specificity of FRD
      were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the
      positive predictive values (PPV), negative predictive values (NPV), Youden index
      were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and
      specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61%
      respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35
      respectively. Overall, FRD have high values of sensitivity, specificity and
      Youden index. However, this difference failed to statistical significance. FRD
      have comparable diagnostic significance with TCT. Therefore, FRD might serve as
      one effective method to screen cervical cancer. Especially for those patients
      living in remote regions of China, where cytology was unavailable. 

PMID- 26221337
TI  - Prognostic role of neuroendocrine cell differentiation in human gastric
      carcinoma.
AB  - The objective of the current study was to investigate the significance and
      biologic characteristic of neuroendocrine cell differentiation (NED) in gastric
      carcinoma by comparing the prognosis and clinicopathologic characteristics
      between patients with or without NED. Retrospective analyses of neuroendocrine
      markers, neuron specific enolase (NSE), chromogranin A (CgA), and synaptophysin
      (Syn) were performed in 174 human gastric carcinoma patients. NED association was
      found in 21.3% gastric carcinoma patients, with or without NED, and was
      correlated with tumor location, cancer emboli, infiltrative depth, TNM stage and
      distant metastasis (P < 0.05 in each case). The 1-year and 3-year survival rate
      of the patients who suffered from gastric carcinoma with NED were significantly
      lower than those without NED. The overall survival time of patients with NED was
      shorter than those with gastric carcinoma without NED, with a significant
      difference between the two types (P = 0.037). Cumulatively, gastric carcinoma
      patients with NED had shorter postoperative survival time and poorer prognosis. 

PMID- 26221338
TI  - Comparison of high ligation and stripping of the great saphenous vein combined
      with foam sclerotherapy versus conventional surgery for the treatment of
      superficial venous varicosities of the lower extremity.
AB  - The aim of this study was to compare the results of high ligation and stripping
      of the great saphenous vein (GSV) trunk combined with foam sclerotherapy with
      conventional surgery for the treatment of superficial venous varicosities of the
      lower extremity. One hundred and thirty eight patients with primary or secondary
      superficial venous varicosities of the lower extremity were included. 60
      underwent conventional surgery and 78 were treated with high ligation and
      stripping of the GSV trunk and foam sclerotherapy of GSV branches, spider veins,
      and reticular veins. Surgical time and amount of bleeding of single limb,
      recurrence of varicose vein, complications and patients satisfactory were
      recorded. Compared with the conventional surgery group, the GSV trunk stripping
      and foam sclerotherapy group had a significantly lower surgical time (P < 0.05),
      amount of bleeding and duration of hospital stays (P < 0.01). No statistically
      significant difference with respect to the wound infection, local discomfort,
      postoperative recurrence rates of varicosity and patients satisfaction score was
      observed (P > 0.05). GSV trunk stripping and foam sclerotherapy group at a 6
      months of follow up had a higher recurrence rate of varicosity as compared to the
      conventional surgery group (P < 0.05). High ligation and GSV trunk stripping
      combined with foam sclerotherapy prior to conventional surgery for patients with
      superficial venous varicosities of the lower extremity with a shorter surgical
      time, fewer bleeding, duration of hospital stays and higher patients satisfactory
      scores. 

PMID- 26221339
TI  - A toll-like receptor 4 (TLR4) variant is associated with asthma severity.
AB  - Asthma is a complex airways disease resulting from the input of both biological
      and environmental factors. Previous studies of single-nucleotide polymorphisms in
      toll-like receptor 4 (TLR4), which produces a protein involved in regulating T
      cell populations, have presented conflicting results regarding its role in asthma
      severity. In the current study, individuals with asthma were genotyped for
      variants of TLR4, and the genotypes were compared with asthma severity and T cell
      subpopulations. TLR4 rs11536879 (A>G) and rs1927907 (G>A) genotypes were
      determined in 350 asthma patients using TaqMan. Asthma severity was graded by
      clinical symptoms, and blood markers and lung function measures were also
      collected. T cell subpopulations were identified from peripheral blood by flow
      cytometry. No significant correlations were observed between genotypes at TLR4
      rs11536879 or rs1927907 and eosinophil counts, total serum IgE, serum
      hypersensitive C-reactive protein, forced expiratory volume in 1 second (FEV1%),
      or FEV1/forced vital capacity (FVC) in asthma patients (P > 0.05). However, the
      GG genotype of rs1927907 was correlated with higher asthma severity (P < 0.05).
      No associations were detected between genotypes at rs11536879 or rs1927907 and
      CD4(+)CD25(high) regulatory T cell counts in peripheral blood from asthmatic
      patients (P > 0.05), but the rs1927907 genotype was associated with TLR4
      expression on the surface of CD4(+)CD25(high) regulatory T cells (P < 0.05).
      Therefore, the TLR4 variant rs1927907 appears to be related to asthma severity
      and TLR4 expression on the surface of CD4(+)CD25(high) regulatory T cells,
      suggesting the potential influence of TLR4 on T cell population balances. 

PMID- 26221340
TI  - ATP citrate lyase expression is associated with advanced stage and prognosis in
      gastric adenocarcinoma.
AB  - Gastric adenocarcinoma (GA) is one of the most common cancer worldwide. ATP
      citrate lyase (ACLY) is generally recognized as a key enzyme of de novo fatty
      acid synthesis responsible for generation of oxaloacetate and cytosolic acetyl
      CoA. This study aimed to investigate the expression level of ACLY in GA and
      evaluate the relationship between ACLY expression and the prognosis of GA
      patients. Paraffin archived samples from 83 GA patients were used to analyze ACLY
      expression by immunohistochemistry. ACLY was significantly upregulated in GA
      tissues compared with adjacent normal tissues (P < 0.001). High ACLY expression
      was correlated with advanced stages (P = 0.007) and lymph node metastasis (P =
      0.022). Furthermore, patients with low ACLY expression had longer survival time
      than those with high ACLY expression (P = 0.031). In conclusion, these results
      indicate that ACLY might serve as a biomarker to predict the progression and
      prognosis of GA patients. 

PMID- 26221341
TI  - Serum galactose-deficient IgA1 levels in children with IgA nephropathy.
AB  - Immunoglobulin A nephropathy (IgAN) is an immunopathologic diagnosis based on a
      renal biopsy, it is characterized by deposits of IgA-containing immune complexes
      in the mesangium. Adults with IgAN have a galactose-deficient IgA1 in the
      circulation and glomerular deposition. There are few studies on the glycosylation
      of serum IgA1 in children with IgAN. To measure the serum levels of galactose
      deficient IgA1 in pediatric patients with IgAN, 72 biopsy-proven IgAN children
      were divided into 3 groups based on the clinical features: isolated hematuria
      group (24 patients), hematuria and proteinuria group (22 patients), and nephritic
      syndrome group (26 patients). They were also divided into 3 groups according to
      pathologic grading: grade I + II group (25 patients), grade III group (33
      patients) and grade IV + V group (14 patients). 30 healthy children were
      recruited as a control group. We used vicia villosa lectin binding enzyme-linked
      immunosorbent assay to measure the serum levels of galactose-deficient IgA1 in
      all groups and controls. Serum levels of galactose-deficient IgA1 in children
      with IgAN were higher than controls (P < 0.01). There were no significant
      differences in serum levels of galactose-deficient IgA1 among the different
      clinical and pathologic grading groups. The values of the area under the curve
      for galactose-deficient IgA1 levels were 0.976 (95% CI, 0.953-1.000). The cutoff
      point for galactose-deficient IgA1 levels was 0.125, with a sensitivity of 87.5%
      and a specificity of 83.3%, with a positive predictive value of 92.6% and a
      negative predictive value of 73.5% (P < 0.01). Children with IgAN presented serum
      galactose-deficient IgA1, which has shown no relationship with the clinical
      manifestations and pathologic grading of the disease. Detection of serum
      galactose-deficient IgA1 levels by vicia villosa lectin binding enzyme-linked
      immunosorbent assay has a certain clinical value in diagnosis of children with
      IgAN. 

PMID- 26221342
TI  - Effects of angiotensin II type 1 receptor antagonist on rats with septic shock.
AB  - AIMS: To investigate the effects of angiotensin II type 1 receptor (AT1R)
      antagonist, losartan, on rats with septic shock induced by endotoxin. METHODS:
      Thirty male SD rats were randomly divided into 3 groups (10 for each group): rats
      were injected with normal saline in C group, lipopolysaccharide (LPS) of 12 mg
      kg(-1) intravenously in LPS group, and losartan of 50 mg kg(-1) intraperitoneally
      followed by LPS of 12 mg kg(-1) intravenously in LOS group. The plasma
      concentrations of nitric oxide (NO), malondialdehyde (MDA), IL-1beta and TNF
      alpha were measured 6 h after LPS administration. Then all the rats were
      sacrificed immediately before the aortas pectoralis were isolated. Inhibitor of
      NF-kappaB (IkappaB) mRNA and its mRNA expressions in aorta were detected.
      RESULTS: The plasma concentrations of NO, MDA, IL-1beta and TNF-alpha were all
      significantly elevated in LPS group compared with the control group (P<0.01),
      which were markedly reduced in LOS group (P<0.01). Both of the mRNA and protein
      expressions of IkappaB in aorta were downregulated after injection of LPS when
      compared with the control group (P<0.01). However, IkappaB mRNA and protein
      expressions in aorta in the LOS group were significantly higher than the LPS
      group (P<0.01). CONCLUSION: AT1R antagonist, losartan, has a reverse effect at
      least partly on circulation dysfunction in rats with septic shock induced by
      endotoxin.

PMID- 26221343
TI  - Associations of genetic polymorphisms of TLR5, TLR9 and transduction molecules in
      MyD88 signaling pathway with systemic lupus erythematosus in Zhuang and Han
      ethnics of Guangxi province, China.
AB  - OBJECTIVES: To discuss the associations of SNPs of TLR5, TLR9 and transduction
      molecules in MyD88 signaling pathway with systemic lupus erythematosus (SLE) risk
      in Zhuang and Han ethnics and to compare the difference between the two ethnics.
      METHODS: PCR and direct sequencing method were used to detect gene polymorphisms
      of TLR5, TLR9 and transduction molecules in MyD88 signaling pathway in 77
      patients with SLE and 72 healthy controls, in order to explore their
      relationships with SLE incidence and compare the differences in genotypes and
      allele frequencies between groups. RESULTS: TLR5 rs5744168 gene polymorphism was
      unrelated with SLE susceptibility of Guangxi Zhuang and Han. Among the Han
      population, there was a statistically significant difference in TLR9 rs352140
      genotype frequency between SLE group and control group (P = 0.043). In the Han
      and Zhuang populations, there were no significant differences in MyD88 rs7744
      genotype and allele frequencies (all P > 0.05) between SLE group and control
      group; but there was a statistically significant difference in allele frequencies
      between the case group and the control group (P = 0.033). For TRAF6 rs5030472, GA
      + AA genotype frequency of Zhuang SLE group was significantly higher than that of
      control group and the difference was statistically significant (P = 0.006); an
      allele frequency was also significantly higher. IRF5 rs2004640 GG/TT genotype and
      the corresponding G allele frequencies of Zhuang SLE group were significantly
      higher than that of control group, with statistically significant differences (P
      = 0.008 and P = 0.000, respectively). CONCLUSION: TLR5 rs5744168 gene
      polymorphism may have no correlation with SLE susceptibility in Guangxi Zhuang
      and Han populations; TLR9 rs352140 gene polymorphism may be associated with SLE
      susceptibility in Guangxi Han population, while TRAF6 rs5030472 and IRF5
      rs2004640 gene polymorphisms may relate to SLE susceptibility in Guangxi Zhuang
      population.

PMID- 26221344
TI  - Application of loop-mediated isothermal amplification (LAMP) assay for the rapid
      diagnosis of pathogenic bacteria in clinical sputum specimens of acute
      exacerbation of COPD (AECOPD).
AB  - The present study explores the application of LAMP for rapid diagnosis of
      pathogenic bacteria in clinical sputum specimens of AECOPD as compared with
      conventional sputum culturing method. 120 sputum specimens of AECOPD patients, 46
      sputum specimens of healthy controls, as well as 166 serum specimens as negative
      controls, were evaluated by LAMP assay using primers of eight typical respiratory
      pathogens. No cross-reactivity was observed in these negative control species
      using LAMP assay. The lower detection limit of LAMP assay was approximately 10(3)
      copies. 25 cases (20.8%) were detected at least one positive bacteria species by
      conventional sputum culturing method, while 73 cases (60.8%) were tested positive
      in LAMP assay. Moreover, compared with sputum culture, bacterial titers results
      of LAMP assay were more consistent with FEV1/FVC value of AECOPD patients. These
      results indicated that the sensitivity of LAMP assay was significantly higher
      than that of sputum culturing method. 

PMID- 26221345
TI  - A complex insertion/deletion polymorphism in the compositionally biased region of
      the ZFHX3 gene in patients with coronary heart disease in a Chinese population.
AB  - Coronary heart disease (CHD) is a leading cause of morbidity and mortality around
      the world and has both genetic and environmental precipitants. Genetic factors
      are significant in determining the level of risk factors in individuals. Variants
      in ZFHX3 gene are associated with atrial fibrillation in individuals of European
      ancestry. The aim of this study was to analyze the polymorphisms in the
      compositionally biased region of the ZFHX3 gene in patients with coronary heart
      disease in a Chinese population, and to explore their associations with coronary
      heart disease. We recruited 278 CHD patients and 358 age and sex matched healthy
      controls in a Chinese Han population, polymorphisms in the compositionally biased
      region of the ZFHX3 gene were determined by polymerase chain reaction followed by
      DNA sequencing. The genotype frequencies were calculated, and statistical
      analysis was performed using the non-parametric mood median test. A complex
      insertion/deletion polymorphism was identified in the compositionally biased
      region of the ZFHX3 gene in a Chinese population. Six common genotypes
      (GGC)4GGTGGCAGT(GGC)4GGT(GGC)8, (GGC)4GGTGGCAGT(GGC)5GGT(GGC)8,
      (GGC)4GGTGGCAGT(GGC)5GGT(GGC)7, (GGC)2GGTGGCAGT(GGC)5GGT(GGC)10,
      (GGC)4GGTGGCAGT(GGC)5GGT(GGC)5, and (GGC)4GGT(GGC)8 were found in both CHD
      patients and healthy controls, there was no significant difference in the six
      genotype frequencies between CHD patients and healthy controls. Rare genotypes
      (GGC)4GGTGGCAGT(GGC)2GGT(GGC)2GGT(GGC)6, (GGC)4GGTGGCAGT (GGC)8,
      (GGC)4GGTGGCAGT(GGC)(3)GGT(GGC)8, and (GGC)6GGT(GGC)8 were only identified in
      healthy controls. Rare genotypes (GGC)4GGTGGCAGT(GGC)4GGT(GGC)5,
      (GGC)4GGTGGCAGT(GGC)4GGT(GGC)4, and (GGC)4GGTGGCGGT(GGC)6 were only found in CHD
      patients. The compositionally biased region of the ZFHX3 gene contains a poly-Gly
      sequence. A complex insertion/deletion polymorphism exists in this region in a
      Chinese population, clinical significance of some rare genotypes should be
      explored for CHD in the future. 

PMID- 26221346
TI  - Lycium barbarum extract provides effective protection against paracetamol-induced
      acute hepatotoxicity in rats.
AB  - The aim of the present study was to investigate the hepatoprotective and
      antioxidant effects of Lycium barbarum (LB) extract against paracetamol-induced
      acute oxidative stress and hepatotoxicity in rats. The subjects were divided into
      6 groups of 8 rats each. The rats in the LB group were administered a dose of 100
      mg/kg LB extract dissolved in saline via the intraperitoneal route for 7 days.
      Subsequently, after last dose of LB, PCT was given in a single dose of 1 g/kg
      diluted in saline via the oral route. Twenty-four hours later, blood samples were
      drawn from all of the subjects for serum Aspartate aminotransferase (AST),
      Alanine aminotransferase (ALT), Total antioxidant status (TAS) and Total oxidant
      status (TOS) tests, and liver tissue samples were obtained for histopathological
      evaluation. The mean TAS level of the group that was subjected to PCT
      intoxication was significantly lower than those of the other groups.
      Additionally, the mean TOS, Oxidative stress index (OSI), ALT and AST values were
      significantly higher in this group. Though the mean TAS level in the PCT + LB
      group was significantly higher than that of the PCT group, the TOS, OSI, ALT, and
      AST levels were significantly lower. When the PCT + LB group and the PCT only
      group were compared in terms of liver damage during the histopathological
      evaluation, a statistically significant difference was observed in Grade I and
      Grade III damage (P=0.013 and P=0.038, respectively). We conclude that Lycium
      barbarum extract leads to a significant improvement in PCT-induced acute
      hepatotoxicity in terms of the histopathological results, serum oxidative stress
      parameters, and serum liver function marker enzymes. 

PMID- 26221347
TI  - Long-term prognosis and related factors towards patients with acute pulmonary
      thromboembolism.
AB  - This study aims to investigate the long-term prognosis and the affecting factors
      towards the patients with acute pulmonary thromboembolism (APTE). The clinical
      data of 903 PTE patients, diagnosed by the spiral CT pulmonary angiography (CTPA)
      or lung ventilation perfusion scanning when hospitalized in the Second Hospital
      of Hebei Medical University from January 1998 to December 2013, were collected,
      among who 548 patients were performed the long-term follow-up, and the factors
      that would affect the prognosis were statistically analyzed. The univariate
      analysis showed that many factors would affect the prognosis of PTE. The
      multivariate non-conditional logistic regression analysis showed that: the
      relevant factors of re-embolization included the idiopathic pulmonary embolism,
      RVD, D-dimer positive, anticoagulation treatment < 3 months, post-treatment PASP
      > 40 mmHg, the relevant factors of death included the D-dimer positive,
      anticoagulation treatment < 3 months, cTnI positive, post-treatment PASP > 40
      mmHg. RVD and post-treatment PASP > 40 mmHg would increase the risk of chronic
      thromboembolic pulmonary hypertension (CTEPH). The idiopathic pulmonary embolism,
      RVD, D-dimer positive, anticoagulation treatment < 3 months, cTnI positive and
      post-treatment PASP > 40 mmHg were the important factors that would affect the
      long-term prognosis of PTE patients. 

PMID- 26221348
TI  - Association of serum hepatocyte growth factor with pericardial fat volume in
      patients with coronary artery disease.
AB  - Hepatocyte growth factor (HGF), as a metabolic regulator, was shown to be
      secreted by adipose tissue and associated with metabolic syndrome (MS) and
      coronary artery disease (CAD). Pericardial fat, as a visceral fat, was found to
      be a significant predictor of CAD. We investigated the relationship between serum
      HGF levels and pericardial fat volume (PFV) in individuals aged between 40-65
      years without liver or renal diseases, and also without medicine consumption.
      Serum HGF levels were found to be significantly higher in participants with CAD
      than those without CAD (P<0.001). In addition, the serum HGF levels had a
      significant positive correlation with the PFV in all the participants (r=0.485,
      P<0.001). Multivariate linear regression demonstrated that the serum HGF levels
      were significantly associated with PFV (beta value=0.454, P<0.001) after
      adjustment for the metabolic parameters. Further regression assessment found that
      the serum HGF levels were significantly associated with PFV in participants with
      CAD (beta value=0.586, P<0.001). The serum HGF levels were significant and
      independent predictors for determining the presence of CAD (OR=1.002, 95% CI:
      1.000-1.004, P=0.011). This study therefore demonstrated that the serum HGF
      levels positively correlated with PFV in participants with CAD and can therefore
      be a significant predictor for the presence of CAD. 

PMID- 26221349
TI  - Platelet-rich fibrin application in dentistry: a literature review.
AB  - The development of bioactive surgical additives to regulate the inflammation and
      increase the speed of healing process is one of the great challenges in clinical
      research. In this sense, platelet rich fibrin (PRF) appears as a natural and
      satisfactory alternative with favorable results and low risks. The following
      review attempts to summarize the relevant literature regarding the technique of
      using PRF, focusing on its preparation, advantages, and disadvantages of using it
      in clinical applications. PRF alone or in combination with other biomaterials
      seems to have several advantages and indications both for medicine and dentistry,
      due it is a minimally invasive technique with low risks and satisfactory clinical
      results. 

PMID- 26221350
TI  - Which is better to multiple rib fractures, surgical treatment or conservative
      treatment?
AB  - To compare the surgery and conservative treatment of multiple fractured ribs, we
      designed a randomized controlled trial in the single center of thoracic surgery
      ward. After admission condition assessment (general clinical evaluation,
      operation condition assessment, the digital method of pain assessment), the
      selected multiple fractured rib patients were told to choose surgery or
      conservative treatment, according to the patient will undergo surgery or
      conservative treatment. In the acute phase, compared with conservative treatment,
      patients with mechanical ventilation in time (mechanical ventilation time MV)
      (3.7 +/- 1.4 vs. 9.5 +/- 4.3), ICU stay time (8.2 +/- 4.3 vs. 14.6 +/- 3.2),
      total hospitalization days (15.3 +/- 6.4 vs. 26.5 +/- 6.9), the incidence of
      pneumonia (6.7% vs. 19.1%), mortality (1.3% vs. 5.3%) and pain score on patients
      (3.3 vs. 5.8) of surgical treatment group were significant lower (P < 0.05). The
      number of tracheostomy in surgical patients with conservative treatment (4 vs. 7)
      was no statistically significant difference (P > 0.05). In chronic phase, the
      surgical patients compared with patients with conservative treatment in the chest
      wall pain (2.9 +/- 1.2 vs. 5.6 +/- 1.7), chest wall tension (13.3% vs. 57.3%),
      dyspnea (5.3% vs. 22.4%) and chest wall deformity rate (4% vs. 93.5%) were lower
      significantly (P < 0.05). In conclusion, the surgical treatment of multiple
      fractured ribs could ease the acute chest pain, reduce the mechanical ventilation
      time and incidence of pneumonia, shorten the hospitalization days and total
      hospitalization days in the ICU and alleviate the forward chest wall discomfort.
      The speedy recovery and long-term quality of patients' life had improved
      significantly. 

PMID- 26221351
TI  - Study on the association between IL-1beta, IL-8 and IL-10 gene polymorphisms and
      risk of coronary artery disease.
AB  - We aimed to evaluate the role of genetic polymorphisms in IL-1beta, IL-8 and IL
      10 in the risk of coronary artery disease (CAD). We identified 325 patients with
      CAD and 342 control subjects without CAD between January 2013 and December 2014.
      Genotyping of IL-1beta +3954 C/T, IL-1beta -511 C/T, IL-8-251T/A, IL-10-1082A/G
      and IL-10-819C/T was performed in a 384-well plate format on the Sequenom
      MassARRAY platform (Sequenom, San Diego, USA). By Multivariate logistic
      regression analysis, the GG and AG+GG genotypes of IL-10-1082A/G were
      significantly associated with an increased risk of CAD. The ORs (95% CI) for GG
      and AG+GG genotypes were 2.12 (1.32-3.43) and 1.56 (1.14-2.14), respectively.
      Patients carrying the AG+GG genotype of IL-10-1082A/G was associated with an
      increased risk of CAD in those with hypertension, diabetes mellitus and smokers,
      and the ORs (95% CI) were 1.41 (0.93-2.14), 7.13 (2.28-23.56) and 2.12 (1.17
      3.89), respectively. Our study found that IL-10-1082A/G polymorphism is
      associated with an increased risk of CAD, especially in hypertension, diabetes
      mellitus and smokers. 

PMID- 26221352
TI  - Association of polymorphisms in ART3 gene with male infertility in the Chinese
      population.
AB  - The ADP-ribosyltransferase 3 gene (ART3) has been reported to be associated with
      non-obstructive azoospermia (NOA) in the Japanese population. In this study, we
      aim to explore the possible association between the four single nucleotide
      polymorphisms (SNPs) (rs11097230, rs17001385, rs14773 and rs6836703) in ART3 gene
      and male infertility with spermatogenesis impairment in the Chinese population.
      The study population included 321 idiopathic infertile males with azoospermia or
      oligozoospermia and 250 fertile males. Four SNPs of ART3 gene were genotyped
      using the method of SNaPshot. The results showed that an SNP (rs6836703) in the
      intron11 region of ART3 gene is significantly associated with male infertility
      (odds ratio: 0.632, 95% confidence interval: 0.440-0.910). No significant
      associations were found between any of the other three variants (rs11097230,
      rs17001385 and rs14773) in ART3 gene and male infertility. SNP rs6836703 in ART3
      gene may contribute to male infertility risk in the Chinese population. 

PMID- 26221353
TI  - Characterization of immune cells and perforin mutations in familiar venous
      thromboembolism.
AB  - AIM: This study was to carry out exome sequencing in a Han Chinese family with
      venous thromboembolism. METHODS: Three venous thromboembolism (VTE) patients and
      five members from a Han Chinese family were evaluated by exome sequencing.
      RESULTS: Among the 3 VTE patients, mutations of 2 genes including PRF1 and HTR2A
      were identified and predicted to be functionally damaged to their encoded
      proteins. In addition, the PRF1 mutation and the HTR2A mutation identified in our
      study were absent in 100 non-related controls, indicating that venous
      thromboembolism has a genetic component. The R357W mutation is located in the
      membrane attack complex/perforin domain of PRF1 protein, which exists in both the
      perforin. The steps of killing foreign or pathological antigen cells by NK cells,
      CD8 (+)T cells and the membrane attack complex include membrane perforation and
      release of the granzyme, either of which is abnormal can lead to immune
      dysfunction. CONCLUSIONS: The mutations of immune related genes in familial VTE
      might provide new understanding of the pathogenesis of familial venous
      thromboembolism.

PMID- 26221354
TI  - The clinical significance of classical and new emerging determinants of
      adenomyosis.
AB  - OBJECTIVE: The present study aims to analyze the diagnostic accuracy of clinical
      characteristics together with new emerging laboratory markers of adenomyosis.
      METHODS: This study was a retrospective analysis of clinical and laboratory
      characteristics of 99 women who underwent hysterectomies with (study group) or
      without (control group) a diagnosis of adenomyosis, 56 and 43 patients in each
      group, respectively. RESULTS: The women with adenomyosis were more likely to have
      younger age (OR = 1.14, 0.789-0.971 95% CI, P = 0.010), higher parity (OR = 1.81,
      0.308-0.988 95% CI, P = 0.046), higher number of curettage (OR = 1.90, 1.189
      3.041 95% CI, P = 0.007), dysmenorrhea (OR = 117.49, 2.715-5084.883 95% CI, P =
      0.013) and elevated mean platelet volume (OR = 5.17, 2.054-13.028 95% CI, P =
      0.000). After receiver-operating-characteristics curve analysis, using a cut
      point of 8.5 fL, the preoperative mean platelet volume predicted adenomyosis with
      a sensitivity of 56.6% and specificity of 82.6%. CONCLUSIONS: Those findings
      suggest gynecologists to give priority on adenomyosis when premenopausal paraous
      patient with a history of curettages admitted with a complaint of dysmenorrhea
      and elevated levels of MPV.

PMID- 26221355
TI  - Relationship between initial treatment effect of recombinant human growth hormone
      and exon 3 polymorphism of growth hormone receptor in Chinese children with
      growth hormone deficiency.
AB  - The aim of this study is to investigate the frequency distribution of exon 3
      deleted (d3-GHR) genetic polymorphism of growth hormone receptor (GHR) in growth
      hormone deficient (GHD) Chinese children and to explore the correlation between
      the growth promoting effects of recombinant human growth hormone (rhGH) and exon
      3 genetic polymorphism of GHR in GHD children. In this study, 111 GHD (excluded
      small for gestational age) children were treated with rhGH (0.20 mg/kg/week) for
      six months. The body height (Ht), body weight, bone age (BA) and growth velocity
      (GV) were measured before and after six months of treatment. The d3-GHR and full
      length GHR (fl-GHR) were analyzed to detect the frequency distribution of two
      isoforms and their influence on growth promoting effect of rhGH. The results
      indicated that the frequencies of fl/fl, fl/d3 and d3/d3 GHR genotypes were
      67.6%, 18.9% and 13.5%. After six months of GH therapy, there were significant
      differences of DeltaGV (DeltaGV: 10.77+/-3.40 cm/year vs 12.18+/-3.08 cm/year)
      (P<0.05) and DeltaHt (DeltaHt: 5.38+/-1.70 cm vs 6.09+/-1.54 cm) (P<0.05) were
      found among GHD children with different genotypes (fl/fl vs fl/d3 and d3/d3). In
      conclusion, the frequency distribution of three GHR genotypes in 111 Chinese GHD
      children was different from that reported in Caucasian, indicating the existence
      of ethnic difference of exon 3 GHR polymorphism. There was a closely relationship
      between GHR genotypes and growth-promoting effect of rhGH in Chinese GHD
      children. 

PMID- 26221356
TI  - Clinical value of Tei index in pediatric patients with repaired tetralogy of
      Fallot.
AB  - PURPOSE: Tetralogy of Fallot is a congenital heart disease characterized by
      underdevelopment of the right ventricular infundibulum. Present study aimed to
      explore the clinic value of Tei index in assessing right ventricular function of
      pediatric patients with repaired Tetralogy of Fallot. METHODS: A total of 45
      pediatric patients with repaired Tetralogy of Fallot were recruited and
      classified into: group A (Tei index <0.5; n=13, aging 2-12 years), group B (0.5<
      Tei index <0.7; n=19, aging 1-14 years), and group C (Tei index >0.7; n=13, aging
      4-14 years). The right ventricular Tei index value was related to the clinical
      characteristics of Tetralogy of Fallot repair patients. RESULTS: Right
      ventricular Tei index was positively correlated with ventilation time, drainage
      volumes, and negatively with drug assistance and Intensive Care Unit (ICU) stay,
      although time for drug assistance and ICU stay were not statically different
      between group B and group C. There was no significant difference in left
      ventricular ejection fraction. CONCLUSION: Tei index is a sensitive indicator of
      right ventricular dysfunction, and has important clinical value to better our
      understanding of right ventricular function after tetralogy of Fallot repair.

PMID- 26221357
TI  - Soft-tissue facial characteristics of attractive Chinese men compared to normal
      men.
AB  - OBJECTIVE: To compare the facial characteristics of attractive Chinese men with
      those of reference men. MATERIALS AND METHODS: The three-dimensional coordinates
      of 50 facial landmarks were collected in 40 healthy reference men and in 40
      "attractive" men, soft tissue facial angles, distances, areas, and volumes were
      computed and compared using analysis of variance. RESULTS: When compared with
      reference men, attractive men shared several similar facial characteristics:
      relatively large forehead, reduced mandible, and rounded face. They had a more
      acute soft tissue profile, an increased upper facial width and middle facial
      depth, larger mouth, and more voluminous lips than reference men. CONCLUSIONS:
      Attractive men had several facial characteristics suggesting babyness.
      Nonetheless, each group of men was characterized by a different development of
      these features. Esthetic reference values can be a useful tool for clinicians,
      but should always consider the characteristics of individual faces.

PMID- 26221358
TI  - Can blood or follicular fluid levels of presepsin predict reproductive outcomes
      in ART; a preliminary study.
AB  - Many stages of COH protocols are considered to potentiate a state of systemic
      inflammation. The limit beyond which inflammation has negative impacts on the
      formation of conception and the reproductive outcomes are compromised still
      remains unclear. Presepsin is a novel biomarker for diagnosing systemic
      inflammation and sepsis. We aimed to investigate whether plasma and follicular
      fluid presepsin values on oocyte pick-up (OPU) day, embryo transfer (ET) day and
      pregnancy test (PT) days could predict reproductive outcomes during IVF treatment
      in women with UEI. Patients were assigned to two groups according to pregnancy
      test results; pregnant (Group 1) and non-pregnant (Group 2). From all patients
      included in the study, 2 cc of venous blood was sampled on the three days and
      follicular fluid (FF) was collected during oocyte retrieval. Plasma presepsin,
      CRP and WBC values and FF presepsin values were measured and compared between the
      2 groups. There was no significant difference between FF and plasma presepsin
      levels on the OPU day (298+/-797.4 ve 352.9+/-657.1; P=0.701, respectively).
      Plasma WBC, CRP and presepsin levels on the OPU, ET and PT days and FF presepsin
      levels on OPU day were not different between the 2 groups. Plasma presepsin
      course on the separate 3 days were different between the groups. 

PMID- 26221360
TI  - Seroprevalence of Lyme disease and associated risk factors in rural population of
      Beijing.
AB  - A seroepidemiological survey of 801 local residents from 28 villages was
      conducted to assess the seroprevalence of Lyme disease and to identify the risk
      factors of becoming seropositive for Lyme disease in the northern suburb of
      Beijing. Forty-one serum samples were positive for IgG against B burgdorferi and
      the seroprevalence was 5.1% (41/801), indicating that Lyme disease is endemic in
      the rural population. In the multivariable analysis, sowing and harvesting in
      summer (OR, 2.377, 95% CI, 1.233-4.583), weed in the yard (OR, 1.914, 95% CI,
      1.003-3.655) were positively associated with Lyme disease, while wearing
      protective clothes (OR, 0.173, 95% CI, 0.041-0.732) was negatively associated
      with Lyme disease. People living in the area are easily infected just near the
      house or in the cropland. They were barely diagnosed and cured. Without clear
      tick knowledge, the people are at high risk of exposure to tick bite and Lyme
      disease. 

PMID- 26221359
TI  - Phase II clinical trial of palonosetron combined with tropisetron in preventing
      chemotherapy-induced nausea and vomiting.
AB  - The purpose of the study was to evaluate the efficacy and toxicity of
      palonosetron combined with tropisetron in preventing chemotherapy-induced nausea
      and vomiting. A total of 82 non-small cell lung cancer patients undergoing
      Docetaxel combined with Cisplatin were randomly divided into group A and group B.
      The patients were received palonosetron combined with tropisetron (group A, n =
      42) or tropisetron alone (group B, n = 40) before initiation of chemotherapy. The
      nausea degree, antiemetic efficacy and safety after chemotherapy were evaluated.
      Patients were administered for rescue therapy if needed. Results showed no
      significant difference in complete remission rate (CRR) during acute phase (0-24
      h post chemotherapy) between group A and group B (90.48% versus 75%, P > 0.05).
      The CRR of group A during delayed (24-120 h post chemotherapy) and overall phases
      (0-120 h post chemotherapy) were 83.33% and 78.57%, higher than group B (50% and
      42.50%, P < 0.05). AS for the improvement rate of nausea during delayed phase,
      group A is better than group B (57.14% versus 35%, P < 0.05). The adverse drug
      reactions of two groups were mild and generally well tolerated, including
      headache, constipation and abdominal distension, and no statistically significant
      differences were observed. In conclusions, compared to tropisetron alone, the
      therapy of palonosetron plus tropisetron is more effective and safer in
      controlling of nausea and vomiting induced by high emetic risk chemotherapy. 

PMID- 26221361
TI  - Study on the consistency of doctor-report outcomes and patient-report outcomes in
      symptoms of traditional Chinese Medicine: a small sample size trial in diabetics.
AB  - Patient-Reported Outcomes (PROs) data are increasingly common and widely accepted
      in clinical investigations of symptoms. Agreements or differences regarding
      Doctor-Report Outcomes (DROs) VS PROs data are unclear. In this study, we
      conducted a clinical trial and investigated the agreement levels of DROs VS PROs
      in symptoms of diabetics. This study had a parallel self-controlled and double
      blind design. In total, 90 diabetics who presented with the required symptoms
      were enrolled in this study, and 83 patients completed the study. The severity
      (none, mild, moderate, and severe) of each symptom was consistently compared with
      the Visual Analogue Scale (VAS) for the PROs measure and the numerical rating
      scales (NRS) for the DROs measure. The Kappa index was used to test the agreement
      in the variables. Our results show that most of the agreements regarding DROs VS
      PROs were moderate; few were modest and substantial. However, the DROs data
      failed to agree with the PROs data well in which symptoms effective evaluation
      criteria overlapped with the inclusion criteria. We believe this results are
      caused by distortion of information during the doctor's decision process. We
      suggest that the effective evaluation criteria should not be overlapped with the
      inclusion criteria in the DROs design. And if it is unavoidable, PROs design
      should be worth considering. 

PMID- 26221362
TI  - Analysis of factors affecting the prognosis of neonatal cholestasis.
AB  - This study aims to analyse the risk factors affecting prognosis of cholestasis in
      newborns. A four-year prospective cohort study was carried out. Neonates with
      cholestasis were enrolled. The diagnosis of neonatal cholestasis was based on
      jaundice in the newborn period, direct bilirubin > 2 mg/dl, discoloured stool and
      elevated liver enzymes. Liver function tests were consecutively monitored weekly
      during the first month and then monthly until the disease was under control. All
      cases received oral ursodeoxycholic acid and internal medicine comprehensive
      treatment. No invalid case was recorded. According to the efficacy of the
      treatment, all cases were divided into two groups: cure group (group A; n = 69)
      and improved group (group B; n = 5). The clinical data of the two groups were
      compared. Selected patient factors were analysed to determine the risk factors
      affecting the prognosis of cholestasis in newborns. The serum total bilirubin and
      direct bilirubin levels in group B were significantly higher than those in group
      A (P < 0.05). A strong linear correlation was detected between the level of
      direct bilirubin (or total bile acid) and the duration of the disease (r > 0.5, P
      < 0.05). The curative effects on neonatal cholestasis and bacterial infection,
      cytomegalovirus (CMV) infection, venous nutrition (> 7 d) and preterm birth were
      closely related. The above factors were also independent risk factors affecting
      the prognosis of neonatal cholestasis. The direct bilirubin or total bile acid
      level was closely related to the duration of neonatal cholestasis. Bacterial
      infection, CMV infection, venous nutrition (> 7 d) and preterm birth were
      significant risk factors affecting the prognosis of neonatal cholestasis. 

PMID- 26221363
TI  - Anxiety and depression are associated with increased counts and degranulation of
      duodenal mast cells in functional dyspepsia.
AB  - BACKGROUND: Patients with functional dyspepsia (FD) have increased risks for
      psychological dysfunction than healthy peoples. This study aimed to explore the
      roles of psychosocial factors and duodenal mast cells in the pathogenesis of FD.
      MATERIAL AND METHODS: We prospectively included 48 FD patients and 21 age- and
      sex-match healthy volunteers. There were 23 patients with postprandial distress
      syndrome (PDS) and 25 patients with epigastric pain syndrome (EPS). The Hospital
      Anxiety Depression Scale (HADS) was administered to evaluate their psychosocial
      status. Upper endoscopy was performed with biopsy of the mucosa from the bulb of
      duodenum. Mast cells counts and degranulation rates were identified by toluidine
      blue staining. The relationship among the scores of HADS-A (anxiety) and HADS-D
      (depression) and the mast cell counts and degranulation rates were analyzed.
      RESULTS: The scores of HADS-A and HADS-D were significantly higher in PDS and EPS
      patients than the normal controls (P<0.05). The mast cell counts and
      degranulation rates in the duodenum were significantly increased in PDS and EPS
      patients than the controls (P<0.05). In either PDS or EPS patients, the HADS-A
      and HADS-D scores were positively correlated with the mast cell counts and
      degranulation rate. CONCLUSION: FD patients had significantly higher risks for
      anxiety and depression, which may lead to FD through the increased mast cell
      counts and degranulation.

PMID- 26221364
TI  - Safe and efectivef guidance by intracardiac echocardiography for transcatheter
      closure in atrial septal defects.
AB  - BACKGROUND: The aim of this study was to investigate the clinical outcome of
      intracardiac echocardiography (ICE) for transcatheter closure of atrial septal
      defect (ASD) compared with the trans-esophageal echocardiography (TEE) guided
      method. METHODS: From May 2010 to April 2011, 46 patients who underwent ICE
      guided (n=23) or TEE guided (n=23) transcatheter closure of ASD were analyzed
      retrospectively. We compared the demographic characteristic, procedure parameters
      and outcomes between ICE- and TEE-guided groups. RESULTS: No significant
      difference was found between 2 groups on demographic characteristics. Fluoroscopy
      time and procedure time was significantly decreased in ICE guided group than that
      in TEE-guided group. In addition, no significant difference was found on
      treatment outcomes, complications between these 2 groups. CONCLUSION: ICE-guided
      ASD occlusion is safe and effective method, which provides more accurate
      anatomical information, shorter fluoroscopy time and procedure time.

PMID- 26221365
TI  - Association between vitamin D receptor gene polymorphisms and breast cancer in a
      Chinese population.
AB  - OBJECTIVE: The present study aimed to explore the association between vitamin D
      receptor (VDR) genetic polymorphisms and breast cancer risk. METHODS: A total of
      219 patients with breast cancer and 321 cases of females without breast cancer
      were enrolled for the present study. PCR-RFLP method was used to genotype 3 SNPs
      of the VDR gene (rs1544410, rs7975232 and rs731236). ELISA method was used to
      detect the amount of 1,25(OH)2D3 in the plasma. The results were analyzed using
      SPSS 17.0 software. RESULTS: We found rs7975232 was associated with breast cancer
      risk. Compared with GG genotype carriers, TT subjects had a lower risk of breast
      cancer (P = 0. 004, OR = 0.774, 95% CI: 0.212~0.955). However, there was no
      difference in 1,25(OH)2D3 levels among the different genotypes. In addition, the
      distribution frequency of the haplotype A-G-T in the patients group was 4.4%,
      significantly higher than the control group (0.7%, P = 0.003; OR=2.643, 95% CI:
      1.631~7.012), while the distribution of haplotype G-T-T in the patient group was
      significantly lower than in the control group (17.3% vs. 28.4%, P = 0.011, OR =
      0.543, 95% CI: 0.325~0.854). CONCLUSIONS: The VDR gene was associated with breast
      cancer pathogenesis; females carrying the haplotype G-T-T had a lower breast
      cancer risk, while the haplotype A-G-T conferred a higher risk.

PMID- 26221366
TI  - Comparison of endoscopic papillary balloon dilatation with conventional
      endoscopic sphincterotomy for peripapillary choledochoduodenal fistula with bile
      duct stones.
AB  - BACKGROUND: Peripapillary choledochoduodenal fistula (PCDF) is occasionally
      detected during endoscopic retrograde cholangiopancreatography. This study was
      designed to compare perioperative outcomes of the peripapillary
      choledochoduodenal fistula with bile duct stones via endoscopic papillary balloon
      dilatation and conventional endoscopic sphincterotomy. METHODS: We
      retrospectively reviewed 28 patients in whom a diagnosis was made with ERCP of
      benign peripapillary choledochoduodenal fistula between January 2009 and August
      2014. Endoscopic sphincterotomy was performed in 10 patients and endoscopic
      papillary balloon dilation was performed in 18 patients. All clinical data were
      analyzed retrospectively. RESULTS: The median operating time was significantly
      shorter in the EPBD group with a median of 19.78+/-4 mins versus 42.2+/-11.6 mins
      in the EST group (P<0.05). Postoperative complications occurred in five (50%)
      versus one (5.5%) patients in the EST and EPBD groups respectively. There were
      significant differences in postoperative complication rates. The rates of post
      ERCP pancreatitis and perforation were not significantly different between the
      EPBD and EST groups [1/10 (10%) vs 2/18 (11%), P=0.7; 0% vs 0%; respectively].
      There were 2 (20%) bleeding cases in EST group, and no bleeding cases in EPBD
      group. CONCLUSION: EPBD appear to be safe and effective modalities for common
      bile duct stone removal in patients with PCDF.

PMID- 26221367
TI  - A case series of duplicated inferior vena cava: mind the side, or fail to trap!
AB  - PURPOSE: The incidence of duplicated inferior vena cava (IVC) ranges between 0.2
      3%. METHODS: The objective of this report is to showcase malformation of inferior
      vena cava in a series of authors' own case studies. We also discuss the abnormal
      embryogenesis that results in this and the clinical management aspects of
      duplicated IVC. RESULTS: Our findings suggest that it is important to recognize
      congenital anomaly such as duplicated IVC, especially prior to an invasive
      procedure.

PMID- 26221368
TI  - Risk factors and clinical characteristics of in-hospital death in acute
      myocardial infarction with IABP support.
AB  - BACKGROUND: Despite the widespread use of the intra-aortic balloon pump (IABP) in
      acute myocardial infarction (AMI), there were few clinical trials regarding the
      deceased's feature. Therefore, we conducted a study to investigate the clinical
      characteristics and risk factor led to in-hospital deaths among AMI patients with
      IABP support. OBJECTIVE: To investigate the clinical characteristics and risk
      factors of in-hospital death with IABP support in AMI patients. METHODS: The
      clinical data of 572 consecutive IABP supported patients with AMI within 72 hours
      from symptom onset from July 2005 to July 2013 were retrospectively analyzed. The
      evolution of the risk factors of in-hospital death and clinical characteristics
      was compared in 81 non-survivors and the survivors. RESULTS: Non-survivors had a
      more severe clinical profile at admission. Fewer patients were treated with
      emergency reperfusion therapy in the non-survivors group. Cardiogenic shock,
      Mechanical complications, ventricular tachycardia/fibrillation and MODS were much
      common in non-survivors (P<0.001). Multivariate logistic regression analysis
      showed advanced age (>65 years), prolonged time from symptom onset to first
      medical contact (FMC), Killip class III/IV, renal dysfunction(GFR <60 ml/min/1.73
      m(2)), and left ventricular ejection fraction (LVEF) <30% were risk factors
      associated with higher in-hospital mortality. CONCLUSIONS: IABP support may be
      more effective combined with revascularization for AMI patients whose
      hemodynamics is compromised. Patients accompanied with cardiogenic shock and
      other life-threatening complications are often uselesswith IABP support.
      Meanwhile, patient whose hemodynamics parameters have significant response to
      IABP may get benefits with IABP to improve in-hospital survival.

PMID- 26221369
TI  - Cellular prion protein (PrP(C)) and its role in stress responses.
AB  - Investigation of the physiological function of cellular prion protein (PrP(C))
      has been developed by the generation of transgenic mice, however, the
      pathological mechanisms related to PrP(C) in prion diseases such as transmissible
      spongiform encephalopathies (TSEs) are still abstruse. Regardless of some
      differences, most studies describe the neuroprotective role of PrP(C) in
      environmental stresses. In this review, we will update the current knowledge on
      the responses of PrP(C) to various stresses, especially those correlated with
      cell signaling and neural degeneration, including ischemia, oxidative stress,
      inflammation and autophagy. 

PMID- 26221370
TI  - Salivary and serum biomarkers for the study of side effects of aripiprazole
      coprescribed with mirtazapine in rats.
AB  - The aim of this study was to investigate whether the co-administration of
      aripiprazole and mirtazapine could determine weight gain and lipid metabolism
      disorders in Wistar rats, compared to the same side effects produced by
      mirtazapine alone, and the risk of hepatotoxicity due to the combination of the
      two substances. Tumor necrosis factor alpha (TNF-alpha), liver fatty acid binding
      protein (L-FABP/FABP1) and repulsive guidance molecule C/hemojuvelin (RGM-C/HJV)
      levels were determined in serum and in saliva. Also, serum levels for total
      cholesterol (TC), low and high-density lipoprotein (LDL, HDL), triglycerides
      (TG), aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were
      assessed. We found positive and statistically significant correlations between
      serum and salivary levels of TNF-alpha, L-FABP/FABP1 and RGM-C/HJV. Mirtazapine
      determined significantly differences of TNF-alpha and L-FABP serum levels; final
      body weight; TC and LDL levels, leading to higher concentrations than its
      association with aripiprazole. Although not statistically significant,
      mirtazapine group experienced higher values for salivary levels of TNF-alpha, TG
      and ASAT, and lower values for HDL, compared to aripiprazole + mirtazapine group.
      The results suggest that aripiprazole might improve some of the disturbances
      caused by mirtazapine, and that the two drugs combination cause no additional
      alterations in liver function. Also, the findings indicate that TNF-alpha, L
      FABP/FABP1 and RGM-C/HJV levels can be helpful as biomarkers for metabolic
      disturbances and impaired function of hepatocytes, and that their salivary
      determination can replace serum determination. 

PMID- 26221371
TI  - Effect of essential oil of traditional two Saudi mint types and its possible role
      in cardiovascular and throat health.
AB  - Essential Oil (EO) of two Mentha species (popularly used in Saudi Arabia), Mentha
      Longifolia (ML), and Mentha pulegium (MP) was isolated and subjected to inhibit
      LDL oxidation in 22 hypercholestrolemic samples collected from 22 subjects, and
      inhibited of 5 bacterial pathogen in vitro. LDL was isolated by
      ultracentrifugation and enhanced to oxidation with CuSO4 and EO was added to
      prevent this oxidation, free radical scavenging activity was measured (decrease
      50% DPPH radicals). EO content of phenolic and flavonoid was estimated. Five
      bacterial strains infect human throat was tested against EO of ML and MP in
      diffusion agar method. EO of the two herbals possess highly significantresults,
      success to inhibit LDL oxidation (P<0.001 for both herbal than non addition
      against lipid peroxidase, P<0.001 ML better than MP P<0.001), decreased DPPH free
      radicals (P<0.001 for both than control, P<0.001 for ML than MP), and possess
      strong antioxidant activity for ML than MP (polyphenol and flavonoids contents
      was higher in EO of ML than MP, P<0.001). EO of ML possess strong antioxidant and
      antibacterial activity than MP, these attributed to its high flavonoid contents
      enable it to be a good for cardiovascular and throat health. The study supported
      the traditional uses of ML. 

PMID- 26221372
TI  - Association between frequency of blood tests and mortality rate in patients
      undergoing massive blood transfusion: a multicenter study in five regions of
      China.
AB  - In order to provide Chinese clinicians with guidelines for the management of
      massive blood loss, we investigated the correlation between the frequency of
      blood tests and the mortality rate in patients undergoing massive blood
      transfusion (MBT). The aim of this study is to provide Chinese clinicians with
      guidelines for the management of massive blood loss. We retrospectively reviewed
      the medical records of patients who underwent massive blood transfusion (MBT)
      from 20 tertiary hospitals in 5 regions of China. The frequency of blood tests
      performed within 24 or 72 hours was compared between patients infused with < 10
      and >= 10 U of red blood cells (RBC). The correlation between the frequency of
      blood tests and the mortality rate was determined. A high frequency of blood
      tests was associated with a low mortality rate in MBT cases. The frequency of all
      blood tests performed within 24 hours was negatively correlated with the
      mortality rate in patients infused with >= 10 U of RBC, while the frequency of
      blood coagulation tests performed within 72 hours was negatively correlated with
      the mortality rate in both patients infused with >= 10 and < 10 U of RBC. In
      conclusions: Measuring the blood indices frequently within the first 24 hours of
      MBT links to lower mortality rate. Coagulation indices in MBT patients should be
      closely monitored in the long term to help improve survival. 

PMID- 26221373
TI  - Prevalence and influences of hepatitis B virus infection on inflammatory bowel
      disease: a retrospective study in southern China.
AB  - The prevalence of Hepatitis B Virus (HBV) infection in inflammatory bowel disease
      (IBD) has been reported differently across the world. The present study
      retrospectively included 675 consecutive IBD patients (449 Crohn's disease, CD
      and 226 ulcerative colitis,UC) from July 2006 to July 2012. The rates of HBV
      infection (HBsAg-positive) were 13.6%, 16.8% and 13.8% in patients with CD, UC,
      and general population, respectively (P = 0.418). No significant difference in
      clinical characters was found between HBsAg-positive and HBsAg-negative IBD
      patients. The rates of anti-HBc and anti-HBs were 25.4%, 31.2% in CD and 30.1%,
      24.3% in UC patients respectively. Liver function was not affected by the use of
      immunosuppressant in HBsAg-positive IBD patients. Erythrocyte sedimentation rate
      (ESR), Hypersensitivity C-reactive protein (HsCRP) and platelet (PLT) counts were
      significantly lower in HBsAg-positive CD patients when compared with HBsAg
      negative CD patients (P < 0.05). Infliximab was used less often in HBsAg-positive
      than HBsAg-negative CD patients (P = 0.010). Multivariate analysis showed that
      lower platelet counts (OR 0.992; 95% CI: 0.988-0.996, P = 0.000) and less common
      use of infliximab therapy (OR 0.127; 95% CI: 0.017-0.95, P = 0.045) were
      independent risk factors for HBV infection in patients with CD. To conclude, the
      prevalence rate of HBV infection in IBD patients was similar to the general
      population in Southern China. HBV infection does not affect the clinical
      characters and medicine choices in either CD or UC patients. HBsAg-positive CD
      patients have lower platelet counts and less common use of infliximab when
      compared with HBsAg-negative CD patients. 

PMID- 26221374
TI  - Programmed death-1 (PD-1) polymorphism is associated with gastric cardia
      adenocarcinoma.
AB  - Polymorphisms in gene encoding programmed death-1 (PD-1) were suggested to be
      associated with the risk of multiple cancers. To the best of our knowledge, no
      investigation has been carried out for gastric cardia adenocarcinoma (GCA) and PD
      1 polymorphisms. Thus, we studied PD-1 rs10204525 A>G, rs7421861 T>C and
      rs2227982 C>T single nucleotide polymorphisms (SNPs) in 330 GCA cases and 608
      cancer-free controls. Genotypes of PD-1 SNPs were determined by ligation
      detection reaction (LDR) assays. The distributions of the allele and genotype
      were not statistically significant in two groups for the three PD-1 SNPs.
      However, in stratified analyses by various characteristics (eg., age, sex,
      smoking condition and alcohol consumption status), we found a significantly
      increased risk of GCA associated with the PD-1 rs2227982 C>T polymorphism was
      evident among ever drinking cases (TT vs. CC: adjusted OR = 2.53, 95% CI = 1.11
      5.79, P = 0.028; TT+CT vs. CC: adjusted OR = 2.04, 95% CI = 1.01-4.13, P =
      0.047). For the other SNPs, in stratified analyses, no correlation between the
      SNPs and susceptibility of GCA was observed. In conclusion, our results highlight
      that rs2227982 C>T polymorphism in PD-1 gene may contribute to the risk of GCA. 

PMID- 26221375
TI  - Association analysis of genetic variants of adiponectin gene and risk of
      pancreatic cancer.
AB  - Adiponectin is a cytokine exclusively secreted from adipocyte, and could perform
      direct or indirect effects on anti-inflammation and anti-tumor. Previous
      researches have studied the correlation between plasma adiponectin levels and the
      risk of pancreatic cancer. So we aimed at investigating the association of
      genetic variants of adiponectin gene and the risk of pancreatic cancer. In this
      study, we genotyped 6 SNPs of adiponectin gene in a case-control study of
      recruited 172 patients of pancreatic cancer and 181 healthy people in Chinese Han
      population. The results indicated that two of the SNPs had significant
      associations with pancreatic cancer. Of which, the SNP rs1501299C>A decreased the
      risk of PC (P=0.016, OR=0.662 95% CI 0.472-0.928), while rs1065358T>C increased
      the risk of PC (P=0.027, OR=1.421 95% CI 1.040-1.941). Furthermore, in the
      clinical correlation analysis, we found rs1501299 was correlated with tumor size
      (P=0.026), cigarette smoking (P=0.022) and alcohol consumption (P=0.001) and
      rs1063538 was correlated with alcohol consumption (P=0.026). In conclusion, we
      provided evidences that the variants in adiponectin gene might influence the
      development and progression of pancreatic cancer. 

PMID- 26221376
TI  - The effect of pre-emptive intravenous Dexketoprofen + thoracal epidural analgesia
      on the chronic post-thoracotomy pain.
AB  - Post thoracotomy chronic pain is a severe problem that affects the majority of
      patients and decreases the quality of life. The purpose of this study is to
      evaluate the long-term effects of thoracal epidural levobupivacaine and
      intravenous dexketoprofen analgesia formed pre-emptively on the wound site pain
      after major thoracotomy operations. This randomised, prospective and double-blind
      study was performed with 60 patients undergoing thoracic surgery. Patients were
      divided into three groups; Control Group (Group C), Pre-emptive Epidural Group
      (Group PE) and Pre-emptive Dexketoprofen + Epidural Group (Group PED). Patients
      in the Group C did not receive epidural analgesics and i.v. dexketoprofen before
      and during the operation. 10-15 ml 0.125% levobupivacaine was given to cases in
      Group PE pre-emptively through epidural catheter before the anesthesia induction.
      The cases in Group PED were given 10-15 ml 0.125% epidural levobupivacaine and 50
      mg dexketoprofen with i.v. infusion pre-emptively. The VAS score was found to be
      lower in Group PED during postoperative 24 and 48 hours and before the discharge
      (P<0.05). The VAS score was similar in all groups during the first and third
      months (P>0.05). A statistically significant decrease was determined in the VAS
      score in Group PED during the sixth month, compared to the other groups (P<0.05).
      When the scores of Patient Satisfaction Scale (PSS) of the cases were compared,
      they were found to be higher in Group PED as statistically significant during the
      discharge period (P<0.001). Scores of PSS were higher in Group PED as
      statistically significant during the postoperative month 6 (P = 0.008). Combined
      application of pre-emptive intravenous dexketoprofen and thoracal epidural
      analgesia reduce the chronic post-thoracotomy pain. 

PMID- 26221377
TI  - Correlation of lipid metabolic disturbance with SOCS-3 gene variation in the
      Uygur nationality women in Xinjiang.
AB  - To study the correlation of lipid metabolic disturbance with gene variation of
      suppressor of cytokine signaling 3 (SOCS-3) in the Uygur nationality women in
      Xinjiang. We Selected 1379 Uygur nationality women as research objects and
      proceeded genotype assay for 3 representative loci (rs12953258, rs4969168 and
      rs9914220) to analyze them. There were significant difference in genotypic
      frequency in rs12953258 between lipid metabolic disturbance group and lipid
      embolism group (P=0.032) and between high density lipoprotein cholesterol (HDL-C)
      abnormal and normal group (P=0.029). Logistic regression analysis showed that the
      AA genotype of rs12953258 might be a risk factors of lipid metabolic disturbance
      in the Uygur nationality women in Xinjiang [CC/AA: OR=3.271, 95% CI (1.092
      9.797), P=0.034]. The AA genotype might be associated with HDL-C decrease and
      triacylglycerol increase. The AA genotype Uygur nationality women with abnormal
      body mass index (BMI) were more sensitive to lipid metabolic disturbance disease.
      SOCS-3 gene variation may be associated with lipid metabolic disturbance in the
      Uygur nationality women in Xinjiang, prevalence of lipid metabolic disturbance
      increases significantly in crowd carrying AA genotype with abnormal BMI. 

PMID- 26221378
TI  - Thrombophilic polymorphisms are not associated with disease-free survival in
      breast cancer patients.
AB  - BACKGROUND: Thrombosis is one of the most common complications in cancer
      patients, however the effect of thrombophilic polymorphisms on cancer specific
      survival is still unclear. OBJECTIVES: The aims of the study were to analyze the
      effect of factor V Leiden (FVL), prothrombin (PT) G20210A, and
      methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms on disease-free
      survival (DFS) in breast cancer and to evaluate the proportional odds model.
      METHODS: Relationship between thrombophilic polymorphisms and DFS was evaluated
      in 197 breast cancer patients. Data regarding patient's age, menopausal status,
      tumor size (T), lymph node status (N), cancer stage, tumor grade (G), estrogen
      and progesterone receptors, c-erbB2 expression, MTHFRC677T, FVL, and PTG20210A
      polymorphisms in DFS were examined by log-rank test and multivariate analyses.
      The proportional odds model was tested as an alternative to Cox model because of
      its insufficient proportional hazards assumption. RESULTS: According to log-rank
      test, T, N, G, tumor stage, and c-erbB2 were associated with DFS. T, N, G, and c
      erbB2 were significantly related to DFS by log-normal regression model.
      PTG20210A, MTHFRC677T and FVL polymorphisms were not related to DFS in breast
      cancer (P>0.05). CONCLUSION: Our study suggests that thrombophilic polymorphisms
      are not associated with DFS when the proportional odds model is applied.

PMID- 26221379
TI  - Clinical features and prognosis of paraquat poisoning: a review of 41 cases.
AB  - PURPOSE: Paraquat is a contact herbicide which is highly toxic to human.
      Deliberate self-poisoning with paraquat continues to be a major public health
      concern in many developing countries. This study aimed to evaluate the data on
      cases of acute paraquat poisoning and to compare different variables between
      survivors and non-survivors. METHODS: In this cross sectional study, medical
      records of all paraquat intoxicated patients were reviewed at Taleghani hospital
      of Urmia, Iran, from 2007 to 2013, retrospectively. Demographics, clinical
      features and laboratory findings were evaluated. The variables compared between
      survivors and non-survivors were the amount of paraquat ingested, occurrence of
      vomiting after ingestion, time and place of hospital admission, length of
      hospital stay, leukocytosis, serum creatinine level and the outcomes. RESULTS: A
      total of 41 patients were evaluated. The mean +/- standard deviation of patients'
      age were 31.6+/-16.9 years. The Length of hospital stay was 5.75+/-4.6 days. Most
      poisonings occurred in spring and summer. The in-hospital fatality rate was
      46.3%. Statistically significant associations were found between the outcome of
      patients and the amount ingested (P=0.001), vomiting (P=0.004), early need to
      intensive cares (P=0.009), leukocytosis (P=0.001), serum creatinine levels
      (P=0.001), manifestations of acute hepatic (P<0.001) and respiratory failure
      (P=0.007). CONCLUSION: Ingestion of more than 30 ml, prompt vomiting, early need
      to intensive cares, leukocytosis, and multi-organ failures are major determinants
      for fatal outcome of paraquat poisoning. It may be useful to educate health
      professionals and the general population about the serious consequences of
      exposure to paraquat.

PMID- 26221380
TI  - Medium to long-term curative effects of long-segmental fixation and fusion on
      degenerative scoliosis.
AB  - OBJECTIVE: To evaluate the medium to long-term curative effects of surgical long
      segmental fixation and fusion in degenerative scoliosis (DS). PATIENTS AND
      METHODS: From January 2001 to December 2011, 56 DS patients underwent long
      segmental fixation and fusion. Clinical data, including visual analogue scale
      (VAS) scores, Oswestry disability index (ODI), lumbar lordosis angles, coronary
      Cobb angles and postoperative complications were followed up for 2 to 12 years
      postoperatively. RESULTS: VAS and ODI scores were significantly improved 1 year
      postoperatively compared to the preoperative values (P = 0.000). Coronary Cobb
      angles were significantly improved three months postoperatively (P = 0.001) but
      >= 1 year after surgery there was no further significant improvement compared to
      the preoperative values (P = 0.585). The lumbar lordosis angle was not
      significantly changed postoperatively (P > 0.05). CONCLUSIONS: Favorable medium
      to long-term curative effects can be achieved by long segmental fixation and
      fusion. Ideally, the fixation and fusion segments should be longer than the
      segments affected by scoliosis. The restoration of the lumbar lordosis angle is
      the key to rebuilding sagittal balance, which is closely correlated with a
      patient's clinical symptoms and quality of life.

PMID- 26221381
TI  - In vitro activities of sitafloxacin tested alone and in combination with
      rifampin, colistin, sulbactam, and tigecycline against extensively drug-resistant
      Acinetobacter baumannii.
AB  - OBJECTIVES: To detect the in vitro activities of sitafloxacin alone and in
      combination with rifampin, colistin, sulbactam, and tigecycline against
      extensively drug-resistant Acinetobacter baumannii (XDR-A. baumannii). MATERIALS
      AND METHODS: 24 XDR-A. baumannii strains were isolated from patients' specimens.
      Broth microdilution assay was used to determine the minimum inhibitory
      concentration (MIC) for sitafloxacin, rifampin, colistin, sulbactam, and
      tigecycline against XDR-A. baumannii strains. The checkerboard microdilution
      method was used to determine the in vitro activities of sitafloxacin combined
      with the other four antimicrobial agents. Accordingly, the fractional inhibitory
      concentration (FIC) and FIC index (FICI) were calculated for each of the
      combinations. RESULTS: According to our results, when tested alone, the rate of
      susceptibility for sitafloxacin was 91.67% against XDR-A. baumannii, followed by
      colistin 62.5%, and then tigecycline 54.17%, rifampin 41.67%. Sulbactam, with a
      16.67% rate of susceptibility was the least effective one. On the other hand,
      when tested in combination, all those three combinations except
      tigecycline/sitafloxacin revealed remarkable synergistic effects.
      Colistin/sitafloxacin showed the highest indifference rate. These combination
      regimens could exert addictive or partially-synergistic effects at the sub-MIC
      levels against XDR-A. baumannii strains. CONCLUSION: Sitafloxacin has acceptable
      in vitro activity against XDR-A. baumannii strains as well as tigecycline,
      rifampin and colistin. Compared with single drugs, most of the combinations of
      these antimicrobial agents could exert synergistic and/or partially synergistic
      and/or addictive effects, which might provide a better alternative when treating
      XDR-A. baumannii infections.

PMID- 26221382
TI  - Association between red cell distribution width and P-wave dispersion in patients
      with atrial tachyarrhythmia.
AB  - Although red cell distribution width (RDW) and P-wave dispersion (Pwd) are strong
      independent predictors of atrial tachyarrhythmia (ATa), the association between
      these two factors in the occurrence of ATA has hitherto not been reported. We
      retrospectively analyzed the cases of ATa patients who underwent Holter
      monitoring at our hospital from October 2013 to August 2014. Clinical data
      including RDW and color doppler ultrasonography data were collected, and Pwd was
      calculated from synchronous recording of P-wave intervals of 12-lead
      electrocardiograms. Patients were categorized into three groups in ascending
      order of RDW values. Between-group comparisons yielded significant differences in
      Pwd, left ventricular diastolic diameter (LVDD), and left atrial diameter (LAD; P
      < 0.05). Pearson correlation analysis revealed that the RDW level positively
      correlated with the Kleiger grade of atrial arrhythmia (r = 0.280, P < 0.001),
      Pwd (r = 0.148, P = 0.001), and LAD (r = 0.297, P < 0.001); Pwd positively
      correlated with the Kleiger grade of atrial arrhythmia (r = 0.257, P < 0.001),
      aortic root diameter (r = 0.143, P < 0.002), and LAD (r = 0.201, P < 0.001).
      Binary logistic multiple regression analysis with ATa as the dependent variable
      revealed that Pwd [odds ratio (OR) = 1.024], RDW [OR = 1.215], and aortic root
      diameter [OR = 1.030] were significant risk factors for ATa occurrence. This is
      the first study to establish a correlation between RDW and Pwd in the occurrence
      of ATa; however, further prospective studies using large cohorts are required to
      validate the correlation. 

PMID- 26221384
TI  - The association between NFKB1-94ins/del ATTG polymorphism and non-small cell lung
      cancer risk in a Chinese Han population.
AB  - This study aimed to clarify the influence of a common insertion/deletion
      polymorphism (-94ins/del ATTG, rs28362491) in the Nuclear factor-kappaB1 (NFKB1)
      promoter on non-small cell lung cancer (NSCLC) susceptibility. We genotyped the
      NFKB1 -94ins/del ATTG polymorphism by the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method and assessed the association with
      NSCLC risk, clinicopathological parameters in a case-control study of 421 cases
      and 425 controls. Heterozygous (ID) genotype disclosed a statistically
      significantly increased risk of developing NSCLC (OR = 1.57, 95% CI 1.13-2.19, P
      = 0.007). Homozygous (II) genotype also showed an increased risk of NSCLC (OR =
      1.87, 95% CI 1.27-2.75, P = 0.001). Statistically significant difference was
      observed when the patients and controls were compared according to ID + II versus
      DD (OR = 2.01, 95% CI 1.47-2.76, P<0.001). The I allele was significantly higher
      in the NSCLC cases compared to the controls (52.9% versus 45.1%). The I allele
      was significantly associated with NSCLC risk (OR = 1.37, 95% CI 1.12-1.65, P =
      0.001). There was a significantly higher frequency of ID + II genotypes observed
      in smokers, compared to non-smokers (OR = 1.99, 95% CI 1.22-3.24, P = 0.005) and
      in patients with stage III + IV, compared to stage I + II (OR = 2.16, 95% CI 1.34
      3.49, P = 0.002). This study suggested that NFKB1 -94ins/del ATTG polymorphism
      was significantly associated with NSCLC risk in Chinese Han population. 

PMID- 26221383
TI  - Urinary expression of acute kidney injury biomarkers in patients after RIRS: it
      is a prospective, controlled study.
AB  - OBJECTIVE: To evaluated the damage effects of retrograde intra-renal surgery
      (RIRS) on kidney tissue by measuring kidney injury molecule-1 (KIM-1), neutrophil
      gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG),
      liver-type fatty acid binding protein (LFABP) expression. MATERIAL AND METHODS:
      We enrolled thirty consecutive patients (Group 1) who underwent RIRS that
      presented with renal calculi size < 2 cm. Forty-seven control patients (Group 2)
      with no signs or symptoms of urogenital disease were also enrolled for this
      study. Patients urine KIM-1, NGAL, NAG, and LFABP and creatinine levels were
      determined before the surgery, 2 hours after the surgery, and 24 hours after the
      surgery. RESULTS: Demographic data were established and found to be similar
      between the two groups. Two hours after the surgery KIM-1/Cr and NGAL/Cr levels
      had increased significantly in urine compared to levels before the surgery
      (P:0.04, P:0.02 respectively) and decreased 24 hours after the surgery. The
      NAG/Cr and LFABP/Cr levels did not change significantly after the surgery.
      CONCLUSION: According to acute kidney injury (AKI) markers, this study is
      suggests that RIRS is a safe method , KIM-1/Cr and NGAL/Cr levels were increased
      first 2 hours but returned to initial levels within 24 hours after the surgery.

PMID- 26221385
TI  - Observation of influences of mental health promotion and mental intervention on
      mental health status of professionals.
AB  - OBJECTIVE: To observe the influences of mental health promotion and mental
      intervention on mental health status of professionals. METHOD: 2878 professionals
      for physical examination were selected and randomly divided into treatment group
      and control group, with 1443 professionals and 1435 professionals, respectively.
      Then, the difference of mental health status before and after mental intervention
      between two groups was compared. RESULTS: In treatment group, the proportion of
      people with healthy mental and modest pressure after mental intervention was
      higher than that before mental intervention and that in control group after
      mental intervention (P<0.01); the proportion of people with psychological sub
      heath and moderate pressure after mental intervention was significantly lower
      than that before mental intervention and that in control group after mental
      intervention (P<0.05). There was no significant difference in mental health
      status in control group before and after mental intervention (P>0.05). Mental
      health consciousness, health status, self pressure-relief capability, job
      satisfaction, and happiness index of professionals were up to 63.3%~78.8%.
      CONCLUSIONS: Mental health promotion and mental intervention may significantly
      improve mental health status of professionals.

PMID- 26221386
TI  - Association of CYP2J2 gene polymorphisms with ischemic stroke.
AB  - OBJECTIVE: The present study aims to investigate the relationship between CYP2J2
      gene polymorphisms and ischemic stroke (IS) in a Chinese Han population. METHODS:
      We performed a case-control study including 300 stroke patients and 300 healthy
      control subjects to compare the distribution of genetic polymorphism G-50T in
      CYP2J2 gene. RESULTS: We found GT genotype of G-50T in CYP2J2 gene was associated
      with the risk for IS (13.7% vs. 7.7%, P = 0.037). After adjustment of
      confounders, the difference remains significant (OR = 1.890, 95% CI: 1.042
      3.011). CONCLUSION: CYP2J2 gene polymorphism might increase the risk of stroke in
      Chinese population.

PMID- 26221387
TI  - Factors related to anxiety and depression in patients undergoing adrenalectomy in
      220 Chinese people.
AB  - OBJECTIVE: The aim of this study was to evaluate the factors related to anxiety
      and depression in patients undergoing adrenalectomy. SUBJECTS AND METHODS: From
      October 2011 to October 2014, 220 consecutive inpatients undergoing adrenalectomy
      were enrolled in this study. Documented informed consent for the study was
      obtained from each subject. All subjects completed a detailed questionnaires for
      information of sociodemographics, the Zung self-rating anxiety scale (SAS), the
      Zung self-rating depression scale (SDS) before operations, and three days after
      operations. RESULTS: Univariate analysis showed that preoperative SAS and SDS
      scores were positively related to age (r=0.280, r=0.322, respectively, both
      P<0.001). And a high degree of preoperative anxiety or depression was correlated
      with their low level of educational status, and with the occurrence of religious
      faith. The same negative relation was found between SAS/SDS and level of
      educational status after operation. Multiple regression analysis revealed that
      age and level of educational status were related to preoperative SAS (beta=0.072,
      P<0.05 and beta=-0.838, P<0.05, respectively). The occurrence of laparoscopic
      operation was negatively related to preoperative SDS (beta=-1.932, P<0.05). Age,
      gender and other diseases were related to postoperative SAS. And other diseases
      were also related to postoperative SDS. CONCLUSIONS: The present study suggested
      that age, gender, other diseases, level of educational status, operation method
      were associated with anxiety or depression before or after operations. Individual
      traits should be taken into account when we intervene to treat anxiety and
      depression in patients undergoing adrenalectomy.

PMID- 26221389
TI  - Case studies on local orthodontic traction by minis-implants before implant
      rehabilitation.
AB  - OBJECTIVE: Dentition defect with malocclusion is a common occurrence in the
      clinical work. To restore proper occlusion, preprosthetic corrections of these
      malposed teeth are often indispensible. The use of orthodontic mini-implants as
      temporary anchorage devices provides a plausible treatment for those patients
      with local problems. The aim of this study was to present two cases using local
      orthodontic traction in conjunction with mini-implants to provide necessary
      conditions for implant rehabilitation in three dimensional space. Clinical
      consideration: Two cases who had dentition defect with malocclusion were included
      in the present study. As both of them rejected crown reduction or orthodontics
      treatment, local orthodontic traction by mini-implants was used to restore normal
      space for implant rehabilitation in three dimensions. Careful mechanics analysis
      and personalized mechanical device were under consideration. The results showed
      that the biological responses of the corrected teeth and the surrounding bony
      structures appeared normal and acceptable. Moreover the patients achieved an
      ideal local occlusion with a short treatment time. CONCLUSION: In conclusion
      local orthodontic traction by mini-implants was a less-invasive and short-term
      method with favorable effects and less necessary occlusal adjustments.

PMID- 26221388
TI  - Common allelic variants of the vitamin receptor D gene rs7975232 (ApaI) do not
      influence bone mineral density figures in postmenopausal osteoporotic women.
AB  - This study examined the association between bone mineral density (BMD) and the
      rs7975232 (ApaI) polymorphism of the vitamin receptor D (VDR) gene. The
      polymorphism was detected using the real-time PCR TaqMan method. The rs7975232
      genotype was determined in 274 postmenopausal osteoporotic Spanish women who were
      60.53+/-8.02 years old. The observed genotype frequencies were in agreement with
      Hardy-Weinberg equilibrium (chi(2)=1.85, P=0.1736). There were no significant
      differences in the rs7975232 genotype groups in our total sample of osteoporotic
      women regarding age, years since menopause, height, weight, and BMD at femoral
      neck, femoral trochanter and lumbar spine. Significant differences were found in
      menarche age (aa vs Aa; P=0.008) and BMI (aa vs AA; P=0.029). We conclude that
      the VDR gene rs7975232 polymorphism is not related to figures of bone mineral
      density in postmenopausal osteoporotic Spanish women. 

PMID- 26221390
TI  - Ochronotic arthritis of bilateral knees: a case report.
AB  - Alkaptonuria ochronosis is a rare metabolic disease in which the body does not
      have enough enzyme called homogentisic acid oxidase. Due to the homogentisic acid
      oxidase deficiency, homogentisic acid accumulates in cartilage and connective
      tissues which leads to ochronotic arthritis. We reported a case of bilateral
      ochronotic arthritis verified by clinical presentation, imaging, arthroscopic and
      histological findings. The patient achieved a satisfying therapeutic outcome
      after arthroscopic debridement followed by intra-articular injection of sodium
      haluronate. 

PMID- 26221391
TI  - Spontaneous isolated dissection at renal upper abdominal aortic: a rare case
      report.
AB  - Arterial dissection is defined as a cleavage of the arterial wall caused by
      intramural hematoma. Isolated extra-aortic arterial dissection has been reported
      in renal and carotid arteries in few literatures but suprarenal aorta dissection
      associated with retrograde formation of a giant descending thoracic aneurysm is
      considered very rare. We present a quite unusual case of suprarenal aorta
      dissection associated with retrograde formation of a giant descending thoracic
      aneurysm sparing both renal and mesenteric vessels, without any branch vessel
      involvement or visceral damage. Because of the patient's persistent epigastric
      pain, endovascular celiac artery stent implantation was performed with 3 multiple
      overlapping uncovered stents. Twelve months after the procedure, computed
      tomographic angiography (CTA) of the abdomen showed patency of both celiac stents
      with thrombus formation in the retrograde dissection sac, and the patient
      remained asymptomatic. This case and others in the medical literature suggest
      that endovascular treatment can be feasible in symptomatic patients with
      spontaneous isolated dissection at renal upper abdominal aortic. 

PMID- 26221392
TI  - Left scrotal swelling caused by severe acute pancreatitis in a 38-year-old
      Chinese male.
AB  - Acute pancreatitis can be associated with a variety of complications caused by
      the interaction of the pancreatic fluids with the local structures, and may
      eventually form pseudocysts, ascites, etc. Nevertheless, scrotal swelling caused
      by severe acute pancreatitis was rarely reported due to low incidence or lack of
      recognition. We reported a rare phenomenon that left scrotal swelling caused by
      severe acute pancreatitis in a 38-year-old man. 

PMID- 26221393
TI  - Progesterone reduces inflammation and apoptosis in neonatal rats with hypoxic
      ischemic brain damage through the PI3K/Akt pathway.
AB  - A neonatal rat model with hypoxic ischemic brain damage (HIBD) was established.
      Forty 7-day-old neonatal Wistar rats were randomly divided into four groups: sham
      operation, model, progesterone and Akt inhibitor. Electron microscopy revealed
      that the neonatal rats with HIBD showed neuronal changes. The protein expression
      levels of pAkt, Nuclear factor kappaB (NF-kappaB) and Bcl-2 in the hippocampus
      were detected by immunohistochemistry and Western blot. The neuronal structure
      was normal in the sham operation group after HIBD for 24 h. Cavitation change due
      to hypoxic ischemic brain damage was observed in the neurons of the model group.
      Progesterone treatment improved neuronal damage and cavitation. Neuronal
      cavitation was clearly changed in the Akt inhibitor group. The protein expression
      levels of hippocampal pAkt and Bcl-2 did not significantly change after HIBD,
      whereas that of NF-kappaB increased. Progesterone pre-treatment increased the
      expression levels of pAkt and Bcl-2 but decreased that of NF-kappaB. The protein
      expression levels of pAkt and Bcl-2 decreased in the Akt inhibitor group, whereas
      that of NF-kappaB increased. This result indicates that progesterone can decrease
      inflammation in HIBD, inhibit apoptosis and protect the brain by activating the
      Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling pathway. 

PMID- 26221394
TI  - Radiation therapy for cutaneous blastic plasmacytoid dendritic cell neoplasm: a
      case report and review of the literature.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare tumor that usually
      arises in the skin. Most patients develop skin lesions, which may be isolated and
      subsequently spread to affect the whole body. The prognosis is poor. Although
      BPDCN is usually treated by chemotherapy, radiation therapy is used in some cases
      (e.g., isolated lesions, elderly patients, or patients with comorbidities). The
      overall therapeutic efficacy and dose of radiation therapy remain unknown. We
      herein present a case of successful radiation treatment for BPDCN in a 77-year
      old Japanese patient and describe the results of the first literature review on
      BPDCN of the skin initially treated with radiation therapy. The patient developed
      a raised, tender, pruritic skin lesion on his left forearm and similar multiple
      disseminated lesions on his right shoulder and precordial region. Histological
      and immunohistochemical examination of biopsy specimens of the skin lesions on
      the left forearm and right shoulder established a diagnosis of BPDCN. The other
      multiple skin lesions were considered to be disseminated BPDCN. The patient
      declined chemotherapy and instead elected radiation therapy for the lesion on his
      left forearm (total of 30 Gy). The skin lesion regressed until only pigmentation
      was present on the forearm, but the untreated lesions rapidly expanded. Although
      BPDCN of the skin may respond favorably to initial radiation therapy, it tends to
      recur in the short term. The optimal dose of radiation therapy remains unclear.
      Our findings provide a baseline for future research. 

PMID- 26221395
TI  - Systemic lupus erythematosus accompanying with renal tuberculosis: a case report.
AB  - A 26-year-old woman, with a six-year history of well-controlled systemic lupus
      erythematosus (SLE), complained of urinary frequency and urgency. After failure
      of commonly-used antibiotic therapy, mycobacterium tuberculosis was cultured from
      her urine and renal tuberculosis (TB) was diagnosed. However, she underwent right
      nephrectomy after the combination therapies of prednisone for SLE and anti
      tuberculosis treatment for renal TB failed. To our knowledge, SLE accompanying
      renal TB is rare, and such a rapid deterioration in renal function has never been
      reported. 

PMID- 26221396
TI  - Intracranial aneurysm disappeared after resection of a cardiac myxoma.
AB  - A 67-year-old male was diagnosed as myxoma-related cerebral aneurysm.
      Transthoracic echocardiogram showed a large mass in the left atrium and
      pathological analysis confirmed the diagnosis of myxoma. Cerebral magnetic
      resonance angiography revealed an aneurysm in the right internal carotid artery.
      However, the aneurysm was disappeared amazingly after successful resection of
      cardiac mass. There are a few similar case reports in the literature. Our case
      report illustrates that cerebral aneurysms may be associated with cardiac myxomas
      and that closely follow-up cerebral aneurysms after resection of myxoma is
      necessary. 

PMID- 26221397
TI  - Resection is an effective treatment for recurrent follicular dendritic cell
      sarcoma from retroperitoneum: unusual presentation of a rare tumor.
AB  - Retroperitoneum follicular dendritic cell sarcoma (FDCS) is an extremely rare
      neoplasm. The treatment of this disease is not clear. A 49-year-old Chinese
      female who had been found a 4.4*4 cm retroperitoneum mass by routine physical
      examination was received radical resection. Pathology revealed an inflammatory
      pseudotumor-like follicular dendritic cell tumor. After five years follow-up, a
      new nodule was noted on the tail of pancreas by routine CT evaluation. Re
      resection was performed and pathological examination found a spindle-cell tumor
      with a great quantity of froth histiocytes. Immunohistochemical stains were
      positive for CD35 and CD21 which suggested it was a recurrent FDCS.
      Retroperitoneum FDCS is a very rare tumor. Surgical resection may be the first
      choice for this disease, even for recurrent tumor, if feasible. A relatively good
      prognosis often is achieved when compared with other malignancy. 

PMID- 26221398
TI  - High-dose methotrexate plus temozolomide as a salvage treatment in metastatic
      central nervous system Lymphoma: two cases report and review of literature.
AB  - Temozolomide (TMZ), an alkylating agent, is widely used for treating high-grade
      gliomas and has emerged as a treatment option for primary central nervous system
      lymphoma (PCNSL) because of its good penetration of the blood-brain barrier (BBB)
      and mild toxicity profile. To our knowledge, the role of temozolomide in the
      treatment of lymphoma was confined to PCNSL and its role in lymphoma central
      infiltration has not been reported yet. We describe our experience using a
      combination of high-dose methotrexate and temozolomide (MT) in two metastatic
      central nervous system Lymphoma (CNSL). As far as we know, this is the first case
      report about temozolomide in metastatic CNSL patients and no study to date has
      incorporated investigation of the biology of metastatic CNSL into the treatment
      protocol. Temozolomide may represent a promising new drug for the treatment of
      metastatic CNSL. 

PMID- 26221399
TI  - Chronic myeloid leukemia transformation in a patient with paroxysmal nocturnal
      hemoglobinuria: a rare case report with literature review.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell
      (HSC) disorder arising from a somatic mutation of the X-linked
      phosphatidylinositol glycan complementation class A gene (PIG-A) which leads to
      partial or complete deficiency of glycosyl-phosphatidylinositol (GPI)-linked
      membrane proteins and causes intravascular hemolysis. Its pathophysiological
      links with aplastic anemia (AA) and myelodysplastic syndrome (MDS) have been
      described frequently, and few acute leukemia are proved to be derived from PNH.
      However, PNH with transformation to chronic myeloid leukemia (CML) has never been
      reported. Here, we report a patient initially diagnosed with PNH while 11 years
      later, Ph chromosome and BCR/ABL fusion gene were detected and the patient was
      eventually confirmed the diagnosis of CML. Here, the diagnosis and management of
      the interesting case, as well as questions regarding pathogenesis, are discussed.

PMID- 26221400
TI  - Endometrial adenocarcinoma in spontaneous abortion: two cases and review of the
      literature.
AB  - OBJECTIVES: To report two extremely rare cases of endometrial adenocarcinoma
      established during the first trimester. CASE PRESENTATION: A 40-year-old (gravida
      0, para 0) and 33-year-old (gravida 4, para 0) woman, were diagnosed with a well
      differentiated adenocarcinoma after a dilatation and curettage (D&C) for
      spontaneous abortions at 8 and 9 gestational weeks, respectively. CONCLUSIONS:
      Thirty-six cases of pregnancy-associated endometrial cancer and 20 cases of first
      trimester pregnancy concurrent with endometrial carcinoma have been reported as
      present cases in the literature. Interestingly, 15 including our two cases were
      detected for spontaneous abortions in first-trimester suggesting a causal
      correlation between endometrial adenocarcinoma and spontaneous abortions.
      Repeated D&C and progesterone administration may be appropriate for patients who
      wish to preserve fertility.

PMID- 26221401
TI  - Anesthetic management of a neonate receiving prenatal repair of gastroschisis.
AB  - Gastroschisis requires surgical repair, which is generally performed after birth.
      We report a case in which a fetus with gastroschisis underwent the abdominal wall
      defect repair before birth. To ensure reliable operating conditions for the
      repair (to prevent fetal movement and crying), the fetus received deep anesthesia
      via placental transfer of maternally administered anesthetics. Meanwhile, the ex
      utero intrapartum treatment procedure was performed to ensure fetal oxygen
      supply, which was likely to be compromised by the deep fetal anesthesia. The
      procedure last for 23 minutes and the gastroschisis was successfully repaired
      before the neonate was delivered. Maternal hemodynamics was kept stable during
      this surgical procedure. The prenatal repair of abdominal wall defect is safe for
      the mother and the fetus, which could potentially improve the neonatal outcomes. 

PMID- 26221402
TI  - Complete withdrawal of hepatitis B virus prophylaxis after liver transplantation
      in a recipient at high risk of recurrence.
AB  - With the potent nucleos (t) ide analogues developed, necessity of life-long
      combined prophylaxis against hepatitis B virus (HBV) recurrence after HBV-related
      liver transplantation has been challenged. But complete withdrawal of HBV
      prophylaxis has not been previously observed in patients at high recurrence risk
      who showed active HBV replication before transplant. Herein, we describe a
      patient with positive HBeAg and HBV-DNA at the time of liver transplantation, who
      experienced complete HBV prophylaxis withdrawal after 3 years' application of
      hepatitis B immunoglobulin (HBIG) and entecavir, and showed no HBV recurrence
      during a long term of follow-up. 

PMID- 26221403
TI  - Unanticipated ventilation obstruction due to a defective reinforced endotracheal
      tube.
AB  - Wire-reinforced endotracheal tubes are used to prevent obstruction. Risk factors
      related to reinforced endotracheal tube obstruction were believed to be
      repeatedly used tube and in presence of N2O. In our case, even in free of these
      risk factors, a delayed tube obstruction occurred with the progress of surgical
      duration. This delay suggests that the obstruction was caused by diffusion of
      warm air/oxygen into an initially small defect, especially as the duration of
      surgery progresses. 

PMID- 26221404
TI  - Recombinant human growth hormone in treatment of diabetes: report of three cases
      and review of relative literature.
AB  - To explore the clinical profile and laboratory changes in three patients with
      diabetes mellitus treated with recombinant human growth hormone (rhGH). Results
      showed that the patient in the first case was diagnosed as T1DM according to the
      classical course of disease, weight loss, polyuria, polydispsia, polyphagia, and
      positive GAD-Ab. The second patient's plasma glucose and urine glucose were at a
      high level, then stored immediately with the negative OGTT. But, the level of
      insulin increased significantly suggesting there is insulin resistance. In the
      last case, fasting plasma glucose level was higher than 7.0 mmol/l several times.
      The level of HbA1c increased. In an oral glucose tolerance test (OGTT), fasting
      glucose > 7.0 mmol/l, plasma glucose < 7.8 mmol/l two hours after a 75 g oral
      glucose load. We postulate that the higher than expected incidence of type 2
      diabetes mellitus with GH treatment may be an acceleration of the disorder in
      predisposed individuals. The rhGH therapy may eventually induce transitory
      glucose metabolic disorder in a very small proportion of patients, which was
      restored gradually after the discontinuance of rhGH. 

PMID- 26221405
TI  - Successful diagnosis of hyperpyrexia induced by isoniazid in a child with
      suspected extra-pulmonary tuberculosis.
AB  - A 9-year-old boy received a rifampicin-isoniazid-ethambutol regimen for suspected
      extra-pulmonary tuberculosis, and glucurolactone and vitamin B6 to provide liver
      protection and decrease neurotoxicity associated with isoniazid. Baseline serum
      aminotransferase and total bilirubin levels were within normal limits before anti
      tubercular treatment. After 4 days of treatment, the patient's body temperature
      increased (from 38.0 degrees C to 40.1 degrees C) and on the 11th day of
      treatment, serum chemistry results showed 400 U/L aspartate transaminase, 535 U/L
      alanine aminotransferase and 76.8 MUmol/L total bile acid, which likely indicated
      drug-induced hepatic injury. After discontinuing isoniazid or administering anti
      tubercular therapy without isoniazid, hyperpyrexia gradually resolved;
      hyperpyrexia reappeared following rechallenge with isoniazid. The patient's liver
      function returned to normal after symptomatic treatment. Thus, hyperpyrexia that
      accompanied hepatic injury was considered to be related to isoniazid. This case
      indicated that hyperpyrexia could also appear during anti-tubercular treatment
      owing to its hepatotoxicity. 

PMID- 26221406
TI  - Epidural injection of hydroxyethyl starch in the management of post-dural
      puncture headache: a case series.
AB  - Epidural injection of hydroxyethyl starch may be a suitable alternative for
      treatment of post-dural puncture headache (PDPH) if epidural blood patch is
      contraindicated. We reported eight consecutive female patients with accidental
      dural puncture (ADP), among whom prophylactic or therapeutic epidural injection
      of hydroxyethyl starch was performed. Prophylactic epidural injection of
      hydroxyethyl starch 20 ml was conducted once a day for two days, without
      sufentanil supplementation, and mild PDPH took place in three of four patients.
      Prophylactic epidural injection of hydroxyethyl starch 20 ml combined with
      sufentanil 5 MUg were performed once a day for two days in three patients, and no
      PDPH happened. Therapeutic epidural injection of hydroxyethyl starch 20 ml
      combined with sufentanil 5 MUg were carried out once a day for 3 days in the
      patient whom relatively severe PDPH had occurred. Further prospective studies of
      epidural injection of hydroxyethyl starch in patients with ADP are required to
      create evidence-based clinical guidelines for safe practice. 

PMID- 26221407
TI  - Advantages of an etiology-based method for treating cancer pain: a case report
      and literature review.
AB  - The WHO analgesic guidelines for treatment of cancer pain have been proven safe
      and effective for most patients. However, there is still inadequate analgesia
      following that guideline based on pain degree. CASE REPORT: An 82-year-old man
      with history of right ceruminous gland carcinoma was treated by tumor resection
      following numerous courses of chemotherapy. He developed progressive pain ranging
      from 4 to 8 or 9 on the 0-10 numeric rating scale (NRS) involving the right side
      of face and neck area. Based on the WHO analgesic ladder, the primary
      prescription for the man contained tramal (100 mg/d) and celebrex (400 mg/d).
      However, pain relief was unsatisfied with this prescription even when dose of
      tramal increased to 200 mg/d. Then, tramal was replaced with morphine sulfate
      tablets at 15 mg at every 8 hours, but the pain was only modest relieved. After
      revaluation by pain physicianbased on etiology and mechanism of pain using ID
      pain questionnaire, the patient was identified to experiencing neuropathic pain.
      Finally, the pain was successfully relieved by gabapentin as an adjuvant to
      tramal. CONCLUSIONS: The successful pain relief of the patient in this case
      indicates that treatment of pain that based on mechanism might be worth
      promoting. According to the etiology of pain, specific drugs or measures should
      be selected for the individual patient. This approach have certain advantages,
      such as timely pain relief, reduction of medical cost, and effective improvement
      of life quality of cancer patients.

PMID- 26221408
TI  - Clavien-Dindo classification and risk factors of gastrectomy-related
      complications: an analysis of 1049 patients.
AB  - OBJECTIVE: The objective of the present study was to explore the major risk
      factors of surgical complications using the Clavien-Dindo classification.
      METHODS: The case-control design was used. A total of 1049 patients who underwent
      radical gastrectomy in Hunan Cancer Hospital between October 2010 and August 2014
      were retrospectively analyzed, including 122 patients (11.6%) with complications
      and 927 patients (88.4%) with no complications. Risk factors were evaluated.
      RESULTS: Following radical gastrectomy, 122 patients (11.6%) experienced a total
      of 151 complications. The incidence of Stages II, IIIa, IIIb, IVa, IVb and V
      complications was 9.6% (n = 101), 2.5% (n = 26), 1.0% (n = 11), 0.8% (n = 8), 0%
      (n = 0), and 0.5% (n = 5), respectively. The incidence of severe complications
      (Stage >= IIIa) was 4.8% (n = 50). Multivariate analysis showed that combined
      resection (Odds Ratio [OR] = 3.36, 95% confidence interval [CI]: 1.71~6.60, P <
      0.01), perioperative blood transfusion (OR = 2.13, 95% CI: 1.38-3.29, P < 0.01),
      and BMI >= 25 kg/m(2) (OR = 1.98, 95% CI: 1.16-3.40, P = 0.01) were independent
      risk factors of complications. CONCLUSIONS: Combined resection, perioperative
      blood transfusion, and BMI >= 25 kg/m(2) are positively correlated with
      complications.

PMID- 26221409
TI  - Statin use and risk of fracture: a meta-analysis.
AB  - This meta-analysis investigates the associations of statins use and fracture
      risk. Two reviewers independently searched six databases including PubMed,
      Cochrane Library, Ovid, Embase, China National Knowledge Infrastructure (CNKI)
      and Wanfang databases. Studies retrieved from database searches were screened
      using our stringent inclusion and exclusion criteria. A sum of 17 studies,
      published between 2000 and 2014, were included in this meta-analysis. The results
      of this meta-analysis suggested that statins use was associated with a decreased
      risk of fracture (OR=0.80; 95% CI, 0.73-0.88; P < 0.00001). In the subgroup
      analysis by study design, statins was significantly associated with a decreased
      risk of fracture in both case-control studies (OR=0.67; 95% CI, 0.55-0.87; P <
      0.0001) and cohort studies (OR=0.86; 95% CI, 0.77-0.97; P=0.02). In the female
      subgroup analysis, statins user showed decreased fracture risk (OR=0.76; 95% CI,
      0.63-0.92; P=0.005). In the subgroup analysis by duration of follow-up, studies
      with both long and short duration of follow-up showed decreased risk of fracture
      (OR=0.67; 95% CI, 0.54-0.82; P=0.001 and OR=0.85; 95% CI, 0.74-0.96; P=0.01).
      Studies with large sample size and small sample size showed decreased risk of
      fracture (OR=0.85; 95% CI, 0.77-0.94; P=0.002 and OR=0.65; 95% CI, 0.54-0.78; P <
      0.0001). In conclusion, this meta-analysis suggested a significant association
      between statins use and decreased fracture risk. 

PMID- 26221410
TI  - The effectiveness of the Invisalign appliance in extraction cases using the the
      ABO model grading system: a multicenter randomized controlled trial.
AB  - OBJECTIVE: The aim of this study was to assess treatment outcomes of the
      Invisalign and compare results with braces. METHODS: One hundred and fifty-two
      adult orthodontic patients, referred to two Orthodontic Specialist Clinics, were
      randomized to receive either invisalign or brace treatment. All patients were
      evaluated by using methods from the American Board of Orthodontics Phase III
      examination. The discrepancy index was used to analyze pretreatment records to
      control for initial severity of malocclusion. The objective grading system was
      used to systematically grade posttreatment records. The Wilcoxon 2-sample tests
      were used to evaluate treatment outcome of Invisalign and braces. RESULTS: The
      total mean scores of the objective grading system categories were improved after
      treatment in both groups. The improvements were not statistically significant in
      scores for alignment, marginal ridges, occlusal relations, over jet, inter
      proximal contacts, and root angulation. Invisalign scores were consistently lower
      than braces scores for buccolingual inclination and occlusal contacts.
      CONCLUSIONS: The overall improvement in OGS scores indicate that both Invisalign
      and fixed appliances were successful in treating Class I adult extraction cases
      in this sample.

PMID- 26221411
TI  - The comparison of maintenance treatment with capecitabine (CMT) and non
      maintenance treatment with capecitabine (non-CMT) in patients with metastatic
      breast cancer.
AB  - AIM: The study examined the response rate, response duration and toxicity of
      maintenance treatment (CMT) and non-maintenance treatment with capecitabine (non
      CMT) in metastatic breast cancer (MBC). MATERIAL AND METHODS: Between September
      2009 and July 2013, a group of 82 patients with MBC, who had progressed after
      anthracycline/taxane chemotherapy, was treated with a capecitabine-based
      chemotherapy and divided into two groups. 54 patients received CMT 1.5 g twice a
      day from days 1 to 14, and 28 patients achieved non-CMT. Treatment was continued
      until disease progression or unacceptable toxicity. The median age of patients
      treated with CMT and non-CMT was 57 years (range 38-78) and 50 years (range 37
      77). The evaluation of treatment effect was possible in all patients. RESULTS:
      The overall response rate (ORR) was 29.7% (16 cases), including 3 (5.6%) complete
      responses (CR) and 13 (24.1%) partial responses (PR). Stable disease (SD) was
      observed in 7.4% of patients receiving CMT (54 patients). In the group receiving
      non-CMT, ORR was 3.6% (1 case). The median PFS in CMT group was 36 weeks, while
      in non-CMT group was 24 weeks. The most common adverse event was hematologic
      toxicity (74.1%), with the incidence of grade 1-2/3-4 was 70.4% and 3.7%. Hand
      foot syndrome was the most frequent non-hematologic form of toxicity, occurring
      in 70.4% of cases. There were no treatment-related deaths. CONCLUSIONS: CMT is an
      effective and safe treatment for pretreated metastatic breast cancer patients.
      And CMT appears to be a more efficacious treatment than non-CMT.

PMID- 26221412
TI  - Sunitinib for patients with locally advanced or distantly metastatic
      dermatofibrosarcoma protuberans but resistant to imatinib.
AB  - PURPOSE: This study evaluated the efficacy and adverse effects of Imatinib
      therapy to advanced Dermatofibrosarcoma protuberan (DFSP) and Sunitinib therapy
      to advanced Dermatofibrosarcoma protuberan (DFSP) after Imatinib resistance.
      METHODS: We analyzed the efficacy, adverse effects and survival of 95 patients
      with locally advanced or metastatic DFSP treated by Imatinib between January 2003
      and December 2009, and also analyzed the efficacy and adverse effects of 30
      patients after Imatinib failure between January 2008 and December 2011. RESULTS:
      In all 95 patients treated by Imatinib, 16 had complete response (CR, 16.8%), 44
      had partial response (PR, 46.3%), 23 had stable disease (SD, 24.2%) and 12 had
      progressive disease (PD, 12.6%). The DCR (CR+PR+SD) was 87.4%. The median PFS was
      23 months and the OS was 40 months. For 30 patients had Sunitinib treatment after
      Imatinib failure, 2 had CR (6.7%), 10 had PR (33.3%), 12 had SD (40%) and 6 had
      PD (20%). The disease control rate (DCR=CR+PR+SD) was 73.3%. The progression free
      survival (PFS) of CR and PR patients were 22 months and 20 months respectively.
      The PFS of 12 SD was 18 months, and overall survival (OS) was 28 months. And the
      median PFS and OS of all 30 patients were 19 and 27 months respectively after
      Sunitinib treatment. Most of the Imatinib-induced adverse effects are of grade 1
      2, including nausea, water retention/edema, fatigue, etc. CONCLUSION: Imatinib
      has been proven to be effective and well-tolerated in the treatment of locally
      advanced or inoperable patients with DFSP. After Imatinib failure, Sunitinib
      therapy showed good clinical efficacy and tolerated adverse effects as a new
      treatment option for such patients.

PMID- 26221413
TI  - Quantitative assessment of amyotrophic lateral sclerosis with diffusion tensor
      imaging in 3.0T magnetic resonance.
AB  - Diffusion tensor imaging (DTI) was used to measure the fractional anisotropy (FA)
      and apparent diffusion coefficient (ADC) value in amyotrophic lateral sclerosis
      (ALS) patients to determine their diagnostic value. 69 ALS patients and 23
      healthy controls were scanned with DTI sequence in 3.0T MR, and FA and ADC values
      in 18 regions were evaluated. Compared with the controls, the ADC values of
      patients in bilateral centrum semiovale, deep frontal and parietal white matter
      were significantly increased (P < 0.05), while the FA values in cerebral
      peduncle, posterior limb of internal capsule (PLIC), corona radiata,
      centrumsemiovale, bilateral deep frontal white matter, the genu and the splenium
      of the corpus callosum were significantly decreased (P < 0.05). When the FA cut
      off value was set to <= 0.6860 for the cerebral peduncle, sensitivity (SE) and
      specificity (SP) of ALS were 95.7% and 83.9% respectively. When the cut-off value
      was set to <= 0.7085 for PLIC, SE and SP were 95.7% and 85.7% respectively. When
      the cut-off value was set to <= 0.6950 for corona radiata, SE and SP were 100.0%
      and 95.7%, respectively. DTI can be used to quantitatively evaluate injury in ALS
      patients. 

PMID- 26221415
TI  - Calcium Channel Blockers, Progression to Dementia, and Effects on Amyloid Beta
      Peptide Production.
AB  - Previous epidemiologic studies suggest that antihypertensive drugs may be
      protective against cognitive decline. To determine if subjects enrolled in the
      University of Kentucky longitudinal aging study who used antihypertensive drugs
      showed diminished progression to dementia, we used a 3-parameter logistic
      regression model to compare the rate of progression to dementia for subjects who
      used any of the five common categories of antihypertensive drugs to those with
      similar demographic characteristics but who did not use antihypertensives.
      Regression modeling showed that subjects who used calcium channel blockers (CCBs)
      but not the other classes of antihypertensives showed a significant decrease in
      the rate of progression to dementia. Significantly, use of CCBs ameliorated the
      negative effects of the presence of APOE-4 alleles on cognitive decline. To
      determine if CCBs could minimize amyloid beta peptide (Abeta(1-42)) production,
      H4 neuroglioma cultures transfected to overexpress APP were treated with various
      CCBs and Abeta(1-42) levels and levels of proteins involved in Abeta production
      were quantified. Results show that treatment with nifedipine led to a significant
      decrease in levels of Abeta(1-42), with no significant decrease in cell
      viability. Collectively, these data suggest that use of CCBs significantly
      diminishes the rate of progression to dementia and may minimize formation of
      Abeta(1-42).

PMID- 26221414
TI  - Mitochondrial Dysfunction Contributes to the Pathogenesis of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease that affects millions of
      people worldwide. Currently, there is no effective treatment for AD, which
      indicates the necessity to understand the pathogenic mechanism of this disorder.
      Extracellular aggregates of amyloid precursor protein (APP), called Abeta peptide
      and neurofibrillary tangles (NFTs), formed by tau protein in the
      hyperphosphorylated form are considered the hallmarks of AD. Accumulative
      evidence suggests that tau pathology and Abeta affect neuronal cells compromising
      energy supply, antioxidant response, and synaptic activity. In this context, it
      has been showed that mitochondrial function could be affected by the presence of
      tau pathology and Abeta in AD. Mitochondria are essential for brain cells
      function and the improvement of mitochondrial activity contributes to preventing
      neurodegeneration. Several reports have suggested that mitochondria could be
      affected in terms of morphology, bioenergetics, and transport in AD. These
      defects affect mitochondrial health, which later will contribute to the
      pathogenesis of AD. In this review, we will discuss evidence that supports the
      importance of mitochondrial injury in the pathogenesis of AD and how studying
      these mechanisms could lead us to suggest new targets for diagnostic and
      therapeutic intervention against neurodegeneration. 

PMID- 26221417
TI  - High-quality permanent draft genome sequence of Rhizobium leguminosarum bv.
      viciae strain GB30; an effective microsymbiont of Pisum sativum growing in
      Poland.
AB  - Rhizobium leguminosarum bv. viciae GB30 is an aerobic, motile, Gram-negative, non
      spore-forming rod that can exist as a soil saprophyte or as a legume
      microsymbiont of Pisum sativum. GB30 was isolated in Poland from a nodule
      recovered from the roots of Pisum sativum growing at Janow. GB30 is also an
      effective microsymbiont of the annual forage legumes vetch and pea. Here we
      describe the features of R. leguminosarum bv. viciae strain GB30, together with
      sequence and annotation. The 7,468,464 bp high-quality permanent draft genome is
      arranged in 78 scaffolds of 78 contigs containing 7,227 protein-coding genes and
      75 RNA-only encoding genes, and is part of the GEBA-RNB project proposal. 

PMID- 26221416
TI  - Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism,
      Bioavailability, and Biological Effects in Animal Models and Humans.
AB  - Plants containing resveratrol have been used effectively in traditional medicine
      for over 2000 years. It can be found in some plants, fruits, and derivatives,
      such as red wine. Therefore, it can be administered by either consuming these
      natural products or intaking nutraceutical pills. Resveratrol exhibits a wide
      range of beneficial properties, and this may be due to its molecular structure,
      which endow resveratrol with the ability to bind to many biomolecules. Among
      these properties its activity as an anticancer agent, a platelet antiaggregation
      agent, and an antioxidant, as well as its antiaging, antifrailty, anti
      inflammatory, antiallergenic, and so forth activities, is worth highlighting.
      These beneficial biological properties have been extensively studied in humans
      and animal models, both in vitro and in vivo. The issue of bioavailability of
      resveratrol is of paramount importance and is determined by its rapid elimination
      and the fact that its absorption is highly effective, but the first hepatic step
      leaves little free resveratrol. Clarifying aspects like stability and
      pharmacokinetics of resveratrol metabolites would be fundamental to understand
      and apply the therapeutic properties of resveratrol. 

PMID- 26221418
TI  - High-quality draft genome sequences of five anaerobic oral bacteria and
      description of Peptoanaerobacter stomatis gen. nov., sp. nov., a new member of
      the family Peptostreptococcaceae.
AB  - Here we report a summary classification and the features of five anaerobic oral
      bacteria from the family Peptostreptococcaceae. Bacterial strains were isolated
      from human subgingival plaque. Strains ACC19a, CM2, CM5, and OBRC8 represent the
      first known cultivable members of "yet uncultured" human oral taxon 081; strain
      AS15 belongs to "cultivable" human oral taxon 377. Based on 16S rRNA gene
      sequence comparisons, strains ACC19a, CM2, CM5, and OBRC8 are distantly related
      to Eubacterium yurii subs. yurii and Filifactor alocis, with 93.2 - 94.4 % and
      85.5 % of sequence identity, respectively. The genomes of strains ACC19a, CM2,
      CM5, OBRC8 and AS15 are 2,541,543; 2,312,592; 2,594,242; 2,553,276; and 2,654,638
      bp long. The genomes are comprised of 2277, 1973, 2325, 2277, and 2308 protein
      coding genes and 54, 57, 54, 36, and 28 RNA genes, respectively. Based on the
      distinct characteristics presented here, we suggest that strains ACC19a, CM2,
      CM5, and OBRC8 represent a novel genus and species within the family
      Peptostreptococcaceae, for which we propose the name Peptoanaerobacter stomatis
      gen. nov., sp. nov. The type strain is strain ACC19a(T) (=HM-483(T); =DSM
      28705(T); =ATCC BAA-2665(T)). 

PMID- 26221419
TI  - Draft genomic sequence of a selenite-reducing bacterium, Paenirhodobacter
      enshiensis DW2-9(T).
AB  - Paenirhodobacter enshiensis is a non-photosynthetic species that belongs to
      family Rhodobacteraceae. Here we report the draft genome sequence of
      Paenirhodobacter enshiensis DW2-9(T) and comparison results to the available
      related genomes. The strain has a 3.4 Mbp genome sequence with G + C content of
      66.82 % and 2781 protein-coding genes. It lacks photosynthetic gene clusters and
      putative proteins necessary in Embden-Meyerhof-Parnas (EMP) pathway, but contains
      proteins in Entner-Doudoroff (ED) pathway instead. It shares 699 common genes
      with nine related Rhodobacteraceae genomes, and possesses 315 specific genes. 

PMID- 26221420
TI  - Draft genome sequence of Methylibium sp. strain T29, a novel fuel oxygenate
      degrading bacterial isolate from Hungary.
AB  - Methylibium sp. strain T29 was isolated from a gasoline-contaminated aquifer and
      proved to have excellent capabilities in degrading some common fuel oxygenates
      like methyl tert-butyl ether, tert-amyl methyl ether and tert-butyl alcohol along
      with other organic compounds. Here, we report the draft genome sequence of M. sp.
      strain T29 together with the description of the genome properties and its
      annotation. The draft genome consists of 608 contigs with a total size of
      4,449,424 bp and an average coverage of 150*. The genome exhibits an average G +
      C content of 68.7 %, and contains 4754 protein coding and 52 RNA genes, including
      48 tRNA genes. 71 % of the protein coding genes could be assigned to COG
      (Clusters of Orthologous Groups) categories. A formerly unknown circular plasmid
      designated as pT29A was isolated and sequenced separately and found to be 86,856
      bp long. 

PMID- 26221421
TI  - Genome sequence of Clostridium sporogenes DSM 795(T), an amino acid-degrading,
      nontoxic surrogate of neurotoxin-producing Clostridium botulinum.
AB  - Clostridium sporogenes DSM 795 is the type strain of the species Clostridium
      sporogenes, first described by Metchnikoff in 1908. It is a Gram-positive, rod
      shaped, anaerobic bacterium isolated from human faeces and belongs to the
      proteolytic branch of clostridia. C. sporogenes attracts special interest because
      of its potential use in a bacterial therapy for certain cancer types. Genome
      sequencing and annotation revealed several gene clusters coding for proteins
      involved in anaerobic degradation of amino acids, such as glycine and betaine via
      Stickland reaction. Genome comparison showed that C. sporogenes is closely
      related to C. botulinum. The genome of C. sporogenes DSM 795 consists of a
      circular chromosome of 4.1 Mb with an overall GC content of 27.81 mol% harboring
      3,744 protein-coding genes, and 80 RNAs. 

PMID- 26221422
TI  - High-quality genome sequence and description of Bacillus dielmoensis strain
      FF4(T) sp. nov.
AB  - Strain FF4(T) was isolated from the skin flora of a 16-year-old healthy
      Senegalese female. This strain exhibited a 16S rRNA sequence similarity of 97.5 %
      with Bacillus fumarioli, the phylogenetically closest species with standing in
      nomenclature and a poor MALDI-TOF-MS score (1.1 to 1.3) that does not allow any
      identification. Using a polyphasic study consisting of phenotypic and genomic
      analyses, strain FF4(T) was Gram-positive, aerobic, rod-shaped, and exhibited a
      genome of 4,563,381 bp (1 chromosome but no plasmid) with a G + C content of 40.8
      % that coded 4,308 protein-coding and 157 RNA genes (including 5 rRNA operons).
      On the basis of these data, we propose the creation of Bacillus dielmoensis sp.
      nov. 

PMID- 26221423
TI  - Resources for Clinicians Becoming Clinician-Educators.

PMID- 26221424
TI  - Designing for the Future: Quality and Safety Education at US Teaching Hospitals.

PMID- 26221425
TI  - New Views: Handheld Ultrasound at the Bedside.

PMID- 26221426
TI  - Clinical Competency Committees and Assessment: Changing the Conversation in
      Graduate Medical Education.

PMID- 26221427
TI  - Global Health Education as a Translational Science in Graduate Medical Education.

PMID- 26221428
TI  - Innovative Scheduling Solutions for Graduate Medical Education.

PMID- 26221429
TI  - Using Google Hangouts on Air for Medical Education: A Disruptive Way to Leverage
      and Facilitate Remote Communication and Collaboration.

PMID- 26221430
TI  - Evaluating Outcomes of Electronic Tools Supporting Physician Shift-to-Shift
      Handoffs: A Systematic Review.
AB  - BACKGROUND: Multiple organizations have recognized that handoffs are prone to
      errors, and there has been an increase in the use of electronic health records
      and computerized tools in health care. OBJECTIVE: This systematic review
      evaluates the current evidence on the effectiveness of electronic solutions used
      to support shift-to-shift handoffs. METHODS: We searched the English-language
      literature for research studies published between January 1, 2008, and September
      19, 2014, using National Library of Medicine PubMed, EBSCO CINAHL, OvidSP All
      Journals, and ProQuest PsycINFO. Included studies focused on the evaluation of
      physician shift-to-shift handoffs and an electronic solution designed to support
      handoffs. We assessed articles using a quality scoring system, conducted a review
      of barriers and strategies, and categorized study outcomes into self-report,
      process, and outcome measures. RESULTS: Thirty-seven articles met inclusion
      criteria, including 20 single group pre- and posttest studies; 8 posttest only or
      cross-sectional studies; 4 nonrandomized controlled trials; 1 cohort study; 1
      randomized crossover study; and 3 qualitative studies. Quality scores ranged from
      3.5 to 14 of a possible 16. Most articles documented some positive outcomes, with
      2 of the 3 studies evaluating patient outcomes yielding statistically significant
      improvements. The only other study that analyzed patient outcomes showed that
      interventions other than the electronic tool were responsible for most of the
      significant improvements. CONCLUSIONS: The majority of studies supported using an
      electronic tool, yet few measured patient outcomes, and numerous studies suffered
      from methodology issues. Future studies should evaluate patient outcomes, improve
      study design, assess the role of faculty oversight, and broaden the focus to
      recognize the role of human factors.

PMID- 26221431
TI  - Mastery of Status Epilepticus Management via Simulation-Based Learning for
      Pediatrics Residents.
AB  - BACKGROUND: Management of status epilepticus (SE) in the pediatric population is
      highly time-sensitive. Failure to follow a standard management algorithm may be
      due to ineffective provider education, and can lead to unfavorable outcomes.
      OBJECTIVE: To design a learning module using high-fidelity simulation technology
      to teach mastery achievement of a hospital algorithm for managing SE. METHODS:
      Thirty pediatrics interns were enrolled. Using the Angoff method, an expert panel
      developed the minimal passing score, which defined mastery. Scoring of simulated
      performance was done by 2 observers. Sessions were digitally recorded. After the
      pretest, participants were debriefed on the algorithm and required to repeat the
      simulation. If mastery (minimal passing score) was not achieved, debriefing and
      the simulation were repeated until mastery was met. Once mastery was met,
      participants graded their comfort level in managing SE. RESULTS: No participants
      achieved mastery at pretest. After debriefing and deliberate simulator training,
      all (n=30) achieved mastery of the algorithm: 30% achieved mastery after 1
      posttest, 63% after a second, and 6.7% after a third. The Krippendorff alpha was
      0.94, indicating strong interrater agreement. Participants reported more self
      efficacy in managing SE, a preference for simulation-based education for learning
      practice-based algorithms of critical conditions, and highly rated the
      educational intervention. CONCLUSIONS: A simulation-based mastery learning
      program using deliberate practice dramatically improves pediatrics residents'
      execution of a SE management protocol. Participants enjoyed and benefited from
      simulation education. Future applications include improving adherence to other
      hospital protocols.

PMID- 26221432
TI  - Five Key Leadership Actions Needed to Redesign Family Medicine Residencies.
AB  - BACKGROUND: New skills are needed to properly prepare the next generation of
      physicians and health professionals to practice in medical homes. Transforming
      residency training to address these new skills requires strong leadership.
      OBJECTIVE: We sought to increase the understanding of leadership skills useful in
      residency programs that plan to undertake meaningful change. METHODS: The
      Preparing the Personal Physician for Practice (P4) project (2007-2014) was a
      comparative case study of 14 family medicine residencies that engaged in
      innovative training redesign, including altering the scope, content, sequence,
      length, and location of training to align resident education with requirements of
      the patient-centered medical home. In 2012, each P4 residency team submitted a
      final summary report of innovations implemented, overall insights, and
      dissemination activities during the study. Six investigators conducted
      independent narrative analyses of these reports. A consensus meeting held in
      September 2012 was used to identify key leadership actions associated with
      successful educational redesign. RESULTS: Five leadership actions were associated
      with successful implementation of innovations and residency transformation: (1)
      manage change; (2) develop financial acumen; (3) adapt best evidence educational
      strategies to the local environment; (4) create and sustain a vision that engages
      stakeholders; and (5) demonstrate courage and resilience. CONCLUSIONS: Residency
      programs are expected to change to better prepare their graduates for a changing
      delivery system. Insights about effective leadership skills can provide guidance
      for faculty to develop the skills needed to face practical realities while
      guiding transformation.

PMID- 26221433
TI  - Use of Emergency Medicine Milestones as Items on End-of-Shift Evaluations Results
      in Overestimates of Residents' Proficiency Level.
AB  - BACKGROUND: The emergency medicine milestones were developed to provide more
      objective resident assessment than current methods. However, little is known
      about the best practices for applying the milestones in resident assessment.
      OBJECTIVE: We examined the utility of end-of-shift evaluations (ESEs) constructed
      using the milestones in resident assessment. METHODS: We developed 14 daily ESEs,
      each of which included 9 or 10 emergency medicine milestones. Postgraduate year
      (PGY)-1 and PGY-2 residents were assessed on milestone levels 1 through 3; PGY-3
      and PGY-4 residents were assessed on levels 3 through 5. Each milestone was rated
      on a nominal scale (yes, no, or not applicable). The Clinical Competency
      Committee combined the ESE data with data from other assessments to determine
      each resident's proficiency level for the emergency medicine subcompetencies. We
      used descriptive statistics to summarize resident ESEs and milestone levels. We
      analyzed differences in ESE score across PGY levels using t tests and analyses of
      variance. RESULTS: Faculty completed 763 ESEs on 33 residents with a range of 2
      to 54 (median=22) ESEs per resident. Faculty rarely (8%, 372 of 4633) rated a
      resident as not achieving a milestone on the ESEs. Analyses of variance revealed
      that ESE scores on level 3 milestones did not differ significantly by PGY level.
      There was poor agreement between ESE scores and Clinical Competency Committee
      ratings. CONCLUSIONS: The ESEs constructed using the milestones resulted in grade
      or milestone inflation. Our results do not support using milestones as a stand
      alone assessment tool.

PMID- 26221434
TI  - Designing a Standardized Laparoscopy Curriculum for Gynecology Residents: A
      Delphi Approach.
AB  - BACKGROUND: Evidence suggests that simulation leads to improved operative skill,
      shorter operating room time, and better patient outcomes. Currently, no
      standardized laparoscopy curriculum exists for gynecology residents. OBJECTIVE:
      To design a structured laparoscopy curriculum for gynecology residents using
      Delphi consensus methodology. METHODS: This study began with Delphi methodology
      to determine expert consensus on the components of a gynecology laparoscopic
      skills curriculum. We generated a list of cognitive content, technical skills,
      and nontechnical skills for training in laparoscopic surgery, and asked 39
      experts in gynecologic education to rate the items on a Likert scale (1-5) for
      inclusion in the curriculum. Consensus was predefined as Cronbach alpha of
      >=0.80. We then conducted another Delphi survey with 9 experienced users of
      laparoscopic virtual reality simulators to delineate relevant curricular tasks.
      Finally, a cross-sectional design defined benchmark scores for all identified
      tasks, with 10 experienced gynecologic surgeons performing the identified tasks
      at basic, intermediate, and advanced levels. RESULTS: Consensus (Cronbach
      alpha=0.85) was achieved in the first round of the curriculum Delphi, and after 2
      rounds (Cronbach alpha=0.80) in the virtual reality curriculum Delphi. Consensus
      was reached for cognitive, technical, and nontechnical skills as well as for 6
      virtual reality tasks. Median time and economy of movement scores defined
      benchmarks for all tasks. CONCLUSIONS: This study used Delphi consensus to
      develop a comprehensive curriculum for teaching gynecologic laparoscopy. The
      curriculum conforms to current educational standards of proficiency-based
      training, and is suggested as a standard in residency programs.

PMID- 26221435
TI  - Coleadership Among Chief Residents: Exploration of Experiences Across
      Specialties.
AB  - BACKGROUND: Many departments have multiple chief residents. How these coleaders
      relate to each other could affect their performance, the residency program, and
      the department. OBJECTIVE: This article reports on how co-chiefs work together
      during the chief year, and what may allow them to be more effective coleaders.
      METHODS: A phenomenological research design was used to investigate experiences
      of outgoing chief residents from 13 specialties at the University of Iowa
      Hospitals and Clinics over a 2-year period from 2012 through 2013. Thematic
      analysis of semistructured interviews was conducted to investigate commonalities
      and recommendations. RESULTS: Face-to-face interviews with 19 chief residents
      from 13 different specialties identified experiences that helped co-chiefs work
      effectively with each other in orienting new co-chiefs, setting goals and
      expectations, making decisions, managing interpersonal conflict, leadership
      styles, communicating, working with program directors, and providing evaluations
      and feedback. Although the interviewed chief residents received guidance on how
      to be an effective chief resident, none had been given advice on how to
      effectively work with a co-chief, and 26% (5 of 19) of the respondents reported
      having an ineffective working relationship with their co-chief. CONCLUSIONS:
      Chief residents often colead in carrying out their multiple functions. To
      successfully function in a multichief environment, chief residents may benefit
      from a formal co-orientation in which they discuss goals and expectations, agree
      on a decision-making process, understand each other's leadership style, and
      receive feedback on their efficacy as leaders.

PMID- 26221436
TI  - Resident Perceptions of Giving and Receiving Peer-to-Peer Feedback.
AB  - BACKGROUND: Peer feedback is increasingly being used by residency programs to
      provide an added dimension to the assessment process. Studies show that peer
      feedback is useful, uniquely informative, and reliable compared to other types of
      assessments. Potential barriers to implementation include insufficient
      training/preparation, negative consequences for working relationships, and a
      perceived lack of benefit. OBJECTIVE: We explored the perceptions of residents
      involved in peer-to-peer feedback, focusing on factors that influence accuracy,
      usefulness, and application of the information. METHODS: Family medicine
      residents at the University of Michigan who were piloting an online peer
      assessment tool completed a brief survey to offer researchers insight into the
      peer feedback process. Focus groups were conducted to explore residents'
      perceptions that are most likely to affect giving and receiving peer feedback.
      RESULTS: Survey responses were provided by 28 of 30 residents (93%). Responses
      showed that peer feedback provided useful (89%, 25 of 28) and unique (89%, 24 of
      27) information, yet only 59% (16 of 27) reported that it benefited their
      training. Focus group participants included 21 of 29 eligible residents (72%).
      Approaches to improve residents' ability to give and accept feedback included
      preparatory training, clearly defined goals, standardization, fewer and more
      qualitatively oriented encounters, 1-on-1 delivery, immediacy of timing, and
      cultivation of a feedback culture. CONCLUSIONS: Residents perceived feedback as
      important and offered actionable suggestions to enhance accuracy, usefulness, and
      application of the information shared. The findings can be used to inform
      residency programs that are interested in creating a meaningful peer feedback
      process.

PMID- 26221438
TI  - Internal Medicine Residents' Perspectives on Receiving Feedback in Milestone
      Format.
AB  - BACKGROUND: In contrast to historical feedback, which was vague or provided
      residents' numerical scores without clear meaning, milestone-based feedback is
      focused on specific knowledge, skills, and behaviors that define developmental
      trajectory. It was anticipated that residents would welcome the more specific and
      actionable feedback provided by the milestone framework, but this has not been
      studied. OBJECTIVE: We assessed internal medicine (IM) residents' perceptions of
      receiving feedback in the milestone framework, particularly assessing perception
      of the utility of milestone-based feedback compared to non-milestone-based
      feedback. METHODS: We surveyed a total of 510 IM residents from 7 institutions.
      Survey questions assessed resident perception of milestone feedback in
      identifying strengths, weaknesses, and trajectory of professional development.
      Postgraduate years 2 and 3 (PGY-2 and PGY-3) residents were asked to compare
      milestones with prior methods of feedback. RESULTS: Of 510 residents, 356 (69.8%)
      responded. Slightly less than half of the residents found milestone-based
      feedback "extremely useful" or "very useful" in identifying strengths (44%),
      weaknesses (43%), specific areas for improvement (45%), and appropriate education
      progress (48%). Few residents found such feedback "not very useful" or "not at
      all useful" in these domains. A total of 51% of PGY-2 and PGY-3 residents agreed
      that receiving milestone-based feedback was more helpful than previous forms of
      feedback. CONCLUSIONS: IM residents are aware of the concepts of milestones, and
      half of the residents surveyed found milestone feedback more helpful than
      previous forms of feedback. More work needs to be done to understand how
      milestone-based feedback could be delivered more effectively to enhance resident
      development.

PMID- 26221437
TI  - Barriers and Facilitators to Effective Feedback: A Qualitative Analysis of Data
      From Multispecialty Resident Focus Groups.
AB  - BACKGROUND: Despite the importance of feedback, the literature suggests that
      there is inadequate feedback in graduate medical education. OBJECTIVE: We
      explored barriers and facilitators that residents in anesthesiology, emergency
      medicine, obstetrics and gynecology, and surgery experience with giving and
      receiving feedback during their clinical training. METHODS: Residents from 3
      geographically diverse teaching institutions were recruited to participate in
      focus groups in 2012. Open-ended questions prompted residents to describe their
      experiences with giving and receiving feedback, and discuss facilitators and
      barriers. Data were transcribed and analyzed using the constant comparative
      method associated with a grounded theory approach. RESULTS: A total of 19
      residents participated in 1 of 3 focus groups. Five major themes related to
      feedback were identified: teacher factors, learner factors, feedback process,
      feedback content, and educational context. Unapproachable attendings, time
      pressures due to clinical work, and discomfort with giving negative feedback were
      cited as major barriers in the feedback process. Learner engagement in the
      process was a major facilitator in the feedback process. CONCLUSIONS: Residents
      provided insights for improving the feedback process based on their dual roles as
      teachers and learners. Time pressures in the learning environment may be
      mitigated by efforts to improve the quality of teacher-learner relationships.
      Forms for collecting written feedback should be augmented by faculty development
      to ensure meaningful use. Efforts to improve residents' comfort with giving
      feedback and encouraging learners to engage in the feedback process may foster an
      environment conducive to increasing feedback.

PMID- 26221439
TI  - Validity and Feasibility of the Minicard Direct Observation Tool in 1 Training
      Program.
AB  - BACKGROUND: Availability of reliable, valid, and feasible workplace-based
      assessment (WBA) tools is important to allow faculty to make important and
      complex judgments about resident competence. The Minicard is a WBA direct
      observation tool designed to provide formative feedback while supporting critical
      competency decisions. OBJECTIVE: The purpose of this study was to collect
      validity and feasibility evidence for use of the Minicard for formative
      assessment of internal medicine residents. METHODS: We conducted a retrospective
      cohort analysis of Minicard observations from 2005-2011 in 1 institution to
      obtain validity evidence, including content (settings, observation rates,
      independent raters); response process (rating distributions across the scale and
      ratings by month in the program); consequences (qualitative assessment of action
      plans); and feasibility (time to collect observations). RESULTS: Eighty faculty
      observers recorded 3715 observations of 73 residents in the inpatient ward (43%),
      clinic (39%), intensive care (15%), and emergency department (3%) settings.
      Internal medicine residents averaged 28 (SD=8.4) observations per year from 9
      (SD=4.1) independent observers. Minicards had an average of 5 (SD=5.1) discrete
      recorded observations per card. Rating distributions covered the entire rating
      scale, and increased significantly over the time in training. Half of the
      observations included action plans with action-oriented feedback, 11% had
      observational feedback, 9% had minimal feedback, and 30% had no recorded plan.
      Observations averaged 15.6 (SD=9.5) minutes. CONCLUSIONS: Validity evidence for
      the Minicard direct observation tool demonstrates its ability to facilitate
      identification of "struggling" residents and provide feedback, supporting its use
      for the formative assessment of internal medicine residents.

PMID- 26221440
TI  - The Standardized Professional Encounter: A New Model to Assess Professionalism
      and Communication Skills.
AB  - BACKGROUND: Physician-patient communication is vital to patient care, and
      physician-nurse interactions are equally critical. Conflict between nurses and
      physicians can greatly impair communication, increasing the risk of treatment
      errors, yet physicians receive little education during training on recognizing
      and resolving professional conflicts. INNOVATION: We created and implemented the
      Standardized Professional (S-Pro) Encounter to improve training and provide
      opportunities to evaluate resident professionalism and communication with health
      care team colleagues. METHODS: The standardized patient model is well established
      for teaching and assessing clinical and communication skills. Using the
      standardized patient concept, we created a nurse-resident encounter with 2
      professionally trained medical portrayers (1 "nurse," 1 "patient"), in which the
      nurse disagrees with the resident's treatment plan. Residents were surveyed for
      prior experience with nurse-physician conflict management, and we assessed
      postencounter for collaborative skills and conflict resolution. RESULTS: All
      residents (n=18) observed at least 1 physician-nurse conflict in front of
      patients. Eleven (61%) reported being involved in at least 1 conflict. Twelve
      residents (67%) had 2 or fewer prior education experiences in interprofessional
      conflict management. Faculty assessment and S-Pro scores demonstrated high
      agreement, while resident self-assessment scores demonstrated low agreement with
      faculty and S-Pro scores. CONCLUSIONS: Participants and evaluators found the
      encounter to be reasonably authentic. There was strong agreement between the
      faculty and S-Pro assessment of resident performance when using the Boggs scale.
      The S-Pro Encounter is easily adapted for other clinical situations or training
      programs, and facilitates the assessment of professionalism and communication
      skills between residents and other health care professionals.

PMID- 26221441
TI  - Evaluation of Surgical Dexterity During the Interview Day: Another Factor for
      Consideration.
AB  - BACKGROUND: Manual dexterity and visual spatial ability are not routinely used to
      evaluate candidates for surgical residency training as part of the application
      interview. OBJECTIVE: This study assessed the acceptability and feasibility of
      evaluating the manual dexterity and visual spatial ability of applicants for
      general surgery and otolaryngology residency, and evaluated the relationship
      between this information and routinely considered application factors. METHODS:
      During the 2012 interview season, medical students applying to our institution's
      general surgery and otolaryngology residency programs underwent a battery of
      tests relevant to surgical dexterity. Five tests shown to be related to the
      surgeons' dexterity or visual spatial skills were administered during the course
      of their in-person interview day. The results from these tests were compared with
      data collected as part of the current application process. RESULTS: A total of 64
      students were enrolled, and 58 had data that could be analyzed. Regression
      analysis using the enter method was performed for each of the tests, and for the
      composite scores. None of the values were significant as defined by P<=.05.
      Neither the scatterplots of the data nor Pearson r showed a correlation between
      the highest performers on the surgical dexterity composite score and individuals'
      highest scores on the dimensions used in the current process to assess
      applicants. CONCLUSIONS: The addition of 1 or more evaluations of visual spatial
      skills and psychomotor aptitude can be done during a standard interview day, is
      acceptable to applicants, and may provide information that is different from the
      usual components of the application.

PMID- 26221442
TI  - Piloting a Structured Practice Audit to Assess ACGME Milestones in Written
      Handoff Communication in Internal Medicine.
AB  - BACKGROUND: Written communication skills are integral to patient care handoffs.
      Residency programs require feasible assessment tools that provide timely
      formative and summative feedback, ideally linked to the Accreditation Council for
      Graduate Medical Education Milestones. OBJECTIVE: We describe the use of 1 such
      tool-UPDATED-to assess written handoff communication skills in internal medicine
      interns. METHODS: During 2012-2013, the authors piloted a structured practice
      audit at 1 academic institution to audit written sign-outs completed by 45
      interns, using the UPDATED tool, which scores 7 aspects of sign-out communication
      linked to milestones. Intern sign-outs were audited by trained faculty members
      throughout the year. Results were incorporated into intern performance reviews
      and Clinical Competency Committees. RESULTS: A total of 136 sign-outs were
      audited (averaging 3.1 audits per intern). In the first trimester, 14 interns
      (31%) had satisfactory audit results. Five interns (11%) had critical
      deficiencies and received immediate feedback, and the remaining 26 (58%) were
      assigned future audits due to missing audits or unsatisfactory scores. In the
      second trimester, 21 interns (68%) had satisfactory results, 1 had critical
      deficiencies, and 9 (29%) required future audits. Nine of the 10 remaining
      interns in the final trimester had satisfactory audits. Faculty time was
      estimated at 10 to 15 minutes per sign-out audited. CONCLUSIONS: The UPDATED
      audit is a milestone-based tool that can be used to assess written sign-out
      communication skills in internal medicine residency programs. Future work is
      planned to adapt the tool for use by senior supervisory residents to appraise
      sign-outs in real time.

PMID- 26221443
TI  - Can Tablet Computers Enhance Faculty Teaching?
AB  - BACKGROUND: Learner benefits of tablet computer use have been demonstrated, yet
      there is little evidence regarding faculty tablet use for teaching. OBJECTIVE:
      Our study sought to determine if supplying faculty with tablet computers and peer
      mentoring provided benefits to learners and faculty beyond that of non-tablet
      based teaching modalities. METHODS: We provided faculty with tablet computers and
      three 2-hour peer-mentoring workshops on tablet-based teaching. Faculty used
      tablets to teach, in addition to their current, non-tablet-based methods.
      Presurveys, postsurveys, and monthly faculty surveys assessed feasibility,
      utilization, and comparisons to current modalities. Learner surveys assessed
      perceived effectiveness and comparisons to current modalities. All feedback
      received from open-ended questions was reviewed by the authors and organized into
      categories. RESULTS: Of 15 eligible faculty, 14 participated. Each participant
      attended at least 2 of the 3 workshops, with 10 to 12 participants at each
      workshop. All participants found the workshops useful, and reported that the new
      tablet-based teaching modality added value beyond that of current teaching
      methods. Respondents developed the following tablet-based outputs: presentations,
      photo galleries, evaluation tools, and online modules. Of the outputs, 60% were
      used in the ambulatory clinics, 33% in intensive care unit bedside teaching
      rounds, and 7% in inpatient medical unit bedside teaching rounds. Learners
      reported that common benefits of tablet computers were: improved
      access/convenience (41%), improved interactive learning (38%), and improved
      bedside teaching and patient care (13%). A common barrier faculty identified was
      inconsistent wireless access (14%), while no barriers were identified by the
      majority of learners. CONCLUSIONS: Providing faculty with tablet computers and
      having peer-mentoring workshops to discuss their use was feasible and added
      value.

PMID- 26221444
TI  - Transforming the Primary Care Training Clinic: New York State's Hospital Medical
      Home Demonstration Pilot.
AB  - BACKGROUND: Training in patient-centered medical home (PCMH) settings may prepare
      new physicians to measure quality of care, manage the health of populations, work
      in teams, and include cost information in decision making. Transforming resident
      clinics to PCMHs requires funding for additional staff, electronic health
      records, training, and other resources not typically available to residency
      programs. OBJECTIVE: Describe how a 1115 Medicaid waiver was used to transform
      the majority of primary care training sites in New York State to the PCMH model
      and improve the quality of care provided. METHODS: The 2013-2014 Hospital Medical
      Home Program provided awards to 60 hospitals and 118 affiliated residency
      programs (training more than 5000 residents) to transform outpatient sites into
      PCMHs and provide high-quality, coordinated care. Site visits, coaching calls,
      resident surveys, data reporting, and feedback were used to promote and monitor
      change in resident continuity and quality of care. Descriptive analyses measured
      improvements in these areas. RESULTS: A total of 156 participating outpatient
      sites (100%) received PCMH recognition. All sites enhanced resident education
      using PCMH principles through patient empanelment, development of quality
      dashboards, and transforming resident scheduling and training. Clinical quality
      outcomes showed improvement across the demonstration, including better
      performance on colorectal and breast cancer screening rates (rate increases of
      13%, P<=.001, and 11%, P=.011, respectively). CONCLUSIONS: A 1115 Medicaid waiver
      is a viable mechanism for states to transform residency clinics to reflect new
      primary care models. The PCMH transformation of 156 sites led to improvements in
      resident continuity and clinical outcomes.

PMID- 26221446
TI  - Low-Cost Simulation: How-To Guide.

PMID- 26221445
TI  - Direct Versus Remote Clinical Observation: Assessing Learners' Milestones While
      Addressing Adolescent Patients' Needs.
AB  - BACKGROUND: Direct clinical observation is an essential component of medical
      trainee assessment, particularly in the era of milestone-based competencies.
      However, the adolescent patient's perspective on this practice is missing from
      the literature. Quality health care is patient centered, yet we did not know if
      our educational practices align with this clinical goal. OBJECTIVE: We sought to
      better understand our adolescent/young adult patients' perspectives of the direct
      observation of our medical trainees in the outpatient clinical setting. METHODS:
      As a quality improvement initiative, we surveyed adolescent/young adult patients,
      medical trainees, and physician observers in our outpatient clinical practice
      regarding their experience following a direct observation encounter. We performed
      descriptive analyses of the data. RESULTS: During a 1-year period, responses were
      received from 23 adolescent/young adult patients, 8 family members, 14 trainees,
      and 6 faculty observers. Nearly all adolescent/young adult patients (n=22) and
      all surveyed family members (n=8) expressed comfort with direct observation, and
      all respondents felt the care they received was the same or better. All
      patient/family respondents preferred direct observation to the idea of remote
      observation, and most, but not all, trainees and faculty observers expressed
      similar opinions. CONCLUSIONS: Adolescent/young adult patients and their family
      members found direct observation of their trainee providers to be comfortable and
      beneficial. Despite adolescent and young adults' facility and comfort with modern
      technologies, there was an expressed preference for direct versus remote
      observation.

PMID- 26221447
TI  - Building the Plane As We Fly It.

PMID- 26221448
TI  - Feedback: Cultivating a Positive Culture.

PMID- 26221449
TI  - Workplace-Based Assessment and Assessment for Learning: Threats to Validity.

PMID- 26221451
TI  - An Innovative Approach to Avoid Reinventing the Wheel: The Anesthesia Education
      Toolbox.

PMID- 26221450
TI  - Induction of General Anesthesia Is in the Eye of the Beholder--Objective Feedback
      Through a Wearable Camera.

PMID- 26221452
TI  - Common Core Curriculum for Quality and Safety: A Novel Instrument for Cultivating
      Trainee Engagement in Quality Improvement and Patient Safety.

PMID- 26221453
TI  - Mapping Quality Improvement and Safety Education to Drive Change Across Training
      Programs.

PMID- 26221454
TI  - Mind the Gap: A Novel Care Transitions Curriculum for Hospitalists and Residents.

PMID- 26221455
TI  - Utilization of an Educational Prescription to Improve Performance on the Internal
      Medicine In-Training Examination.

PMID- 26221456
TI  - The Fellow as Clinical Teacher Curriculum: Enhancing Teaching in the Setting of
      Consultation.

PMID- 26221457
TI  - Exploring Drivers of Medical Overuse Through Transformation of Grand Rounds Into
      "Right Care Rounds".

PMID- 26221458
TI  - A Brief Interprofessional "Guess My Role" Game Improves Residents' Knowledge
      About Team Roles.

PMID- 26221459
TI  - The Senior Prep Conference: Simultaneous Learning and Teaching.

PMID- 26221460
TI  - A Novel, Resident-Led Curriculum for Night Float Rotations.

PMID- 26221461
TI  - Primary Resident Physician: Improving Continuity of Care.

PMID- 26221462
TI  - PACE Palette: Teaching Interpersonal and Communication Skills.

PMID- 26221463
TI  - Academy of Resident Educators: A Framework for Development of Future Clinician
      Educators.

PMID- 26221464
TI  - A Leadership Development Curriculum for Radiology Residency.

PMID- 26221465
TI  - Observations: Restructuring of the Nation's Graduate Medical Education System.

PMID- 26221466
TI  - Observations: Will the ACGME Faculty Scholarly Activity Requirements Promote
      Dishonesty Among Program Directors?

PMID- 26221467
TI  - Comments: ACGME Response.

PMID- 26221468
TI  - Observations: Utilizing an Interactive Case-Based Format for Intern Orientation.

PMID- 26221469
TI  - Observations: A Pilot Study of Multiple Simultaneous Critical Care Simulations.

PMID- 26221470
TI  - Not So Grand Rounds.

PMID- 26221471
TI  - The Clock on the Wall.

PMID- 26221472
TI  - The Need for a Leadership Curriculum for Residents.

PMID- 26221473
TI  - The Program Self-Study and the 10-Year Site Visit: Rationale for a New Approach.

PMID- 26221474
TI  - Erratum.

PMID- 26221475
TI  - Molecular and genetic aspects of odontogenic tumors: a review.
AB  - Odontogenic tumors contain a heterogeneous collection of lesions that are
      categorized from hamartomas to benign and malignant neoplasms of inconstant
      aggressiveness. Odontogenic tumors are usually extraordinary with assessed
      frequency of short of 0.5 cases/100,000 population for every year. The lesions
      such as odontogenic tumors are inferred from the components of the tooth
      structuring contraption. They are discovered solely inside the maxillary and
      mandibular bones. This audit speaks to experiences and cooperation of the
      molecular and genetic variations connected to the development and movement of
      odontogenic tumors which incorporate oncogenes, tumor-silencer genes, APC gene,
      retinoblastoma genes, DNA repair genes, onco-viruses, development components,
      telomerase, cell cycle controllers, apoptosis-related elements, and
      regulators/conttrollers of tooth development. The reasonable and better
      understanding of the molecular components may prompt new ideas for their
      detection and administrating a better prognosis of odontogenic tumors. 

PMID- 26221476
TI  - Resveratrol attenuates visfatin and vaspin genes expression in adipose tissue of
      rats with type 2 diabetes.
AB  - OBJECTIVES: Visfatin and vaspin are secreted by adipose tissue and play key roles
      in glucose homeostasis and subsequently are potential targets for diabetes
      treatment. Resveratrol (RVS) corrects insulin secretion and improves insulin
      sensitivity. We investigated the RVS effects on serum antioxidants, insulin and
      glucose levels, also visfatin and vaspin genes expression in adipose tissue of
      streptozotocin-nicotinamide (STZ-NA) induced type 2 diabetic rats. MATERIALS AND
      METHODS: Diabetes was induced in Wistar rats (n=32) using STZ (60 mg/kg body
      weight) and NA (120 mg/kg body weight); rats were divided into 4 groups (n=8).
      Eight untreated normal rats were used as control group; four diabetic rat groups
      (2-5) were treated with 0, 1, 5 and 10 mg/kg body weight of RVS, respectively for
      30 days. After treatment blood and adipose tissue were prepared from all animals.
      Serum glucose, insulin, HOMA index, total antioxidant capacity (TAC), and
      malondialdehyde (MDA) were measured. Visfatin and vaspin genes expression in
      adipose tissue were evaluated using real-time PCR. RESULTS: RVS reduced blood
      glucose significantly and increased insulin level, resulting in insulin
      sensitivity improvement. Furthermore RVS increased weight and TAC, while reducing
      serum MDA in the diabetic groups. Visfatin gene expression increased in the
      diabetic group, and RVS treatment reduced it. Vaspin gene expression was reduced
      in RVS receiving diabetic groups. CONCLUSION: The results indicated that RVS has
      potential hypoglycemic effect, probably by increasing insulin level and changing
      gene expression of visfatin and vaspin. Moreover RVS showed antioxidant effects
      through reduction in peroxidiation products and augmented antioxidant capacity.

PMID- 26221477
TI  - Juglone exerts antitumor effect in ovarian cancer cells.
AB  - OBJECTIVES: Juglone is isolated from many species of the Juglandaceae family and
      used as an anti-viral, anti-bacterial, and anti-tumor therapeutic. Here, we
      evaluated juglone-induced antitumor effect in ovarian cancer SKOV3 cells.
      MATERIALS AND METHODS: MTT assay was performed to examine juglone anti
      proliferative effect. Cell cycle and apoptosis were studied using flow cytometry
      in juglone-treated SKOV3 cells. To investigate molecular mechanism of cell cycle
      and apoptosis, protein expression levels were measured by Western blot analysis
      of cyclin D1, Bcl-2, Bax, cytochrome c, caspase-9 and caspase-3. To investigate
      the motility of juglone-treated SKOV3 cell, Matrigel invasion assay was employed
      to characterize cell invasion. Also, matrix metalloproteinase-2 (MMP-2)
      expression levels were detected by western blot. RESULTS: Juglone significantly
      inhibited SKOV3 cell proliferation as shown by G0/G1 phase arrest, and this
      effect was mediated by inactivation of cyclin D1 protein (P<0.05). Juglone
      induced apoptosis in SKOV3 cell which was accompanied by caspase-9 and caspase-3
      activation (P<0.05). Juglone decreased Bcl-2 levels and increased Bax and
      cytochrome c (Cyt c) levels (P<0.05). Juglone sufficiently inhibited invasion
      while evidently decreased MMP-2 expression (P<0.05). CONCLUSION: The results
      suggest that juglone could probably induce apoptosis through mitochondrial
      pathway and restrained cell invasiveness by decreasing MMP expression.

PMID- 26221478
TI  - Effect of selegiline on neural stem cells differentiation: a possible role for
      neurotrophic factors.
AB  - OBJECTIVES: The stimulation of neural stem cells (NSCs) differentiation into
      neurons has attracted great attention in management of neurodegenerative disease
      and traumatic brain injury. It has been reported that selegiline could enhance
      the morphologic differentiation of embryonic stem cells. Therefore this study
      aimed to investigate the effects of selegiline on NSCs differentiation with focus
      on the role of neurotrophic factor gene expression. MATERIALS AND METHODS: The
      NSCs were isolated from lateral ventricle of C57 mice brain. The cells were
      exposed to selegiline in nano to micromolar concentrations for 24 hr or 72 hr. In
      order to assay the effect of selegiline on NSCs differentiation into neurons,
      astrocytes and oligodendrocytes, immunocytochemical techniques were utilized.
      Samples were exposed to specific antibodies against neurons (beta tubulin),
      astrocytes (GFAP) and oligodendrocytes (OSP). The expression of BDNF, NGF and NT3
      genes was investigated using Real-Time PCR. RESULTS: Our findings revealed that
      selegiline increased NSCs differentiation into neurons at 10(-7) and 10(-8) M and
      decreased the differentiation into astrocytes at 10(-9), while oligodendrocyte
      did not significantly change in any of the used concentrations. In addition data
      analyses showed that selegiline increased BDNF, NGF and NT3 gene expression at 24
      hr, but did not change them in the other time of exposure (72 hr) except 10(-7) M
      concentration of selegiline, which increased NT3 expression. CONCLUSION: Our
      results indicate selegiline induced the differentiation of NSCs into neurons and
      in this context the role of neurotrophic factors is important and should be
      considered.

PMID- 26221479
TI  - Gardenia jasminoides extracts and gallic acid inhibit lipopolysaccharide-induced
      inflammation by suppression of JNK2/1 signaling pathways in BV-2 cells.
AB  - OBJECTIVES: Gardenia jasminoides Ellis (GJ, Cape Jasmine Fruit, Zhi Zi) has been
      traditionally used for the treatment of infectious hepatitis, aphthous ulcer, and
      trauma; however, the direct evidence is lacking. MATERIALS AND METHODS: We
      investigated the effect of the GJ extract (GJ) and gallic acid (GA) on
      lipopolysaccharide (LPS) induced inflammation of BV-2 microglial cells and acute
      liver injury in Sprague-Dawley (SD) rats. RESULTS: Our results showed that the GJ
      extract and GA reduced LPS-induced nitric oxide (NO), interleukin (IL)-1, IL-6,
      reactive oxygen species (ROS), and prostaglandin (PGE2) production in BV-2 cells.
      The GJ extract and GA significantly decreased serum aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT) levels in LPS-treated rats. Furthermore,
      the water extract, but not the ethanol extract, of the GJ dose-dependently
      inhibited LPS-induced JNK2/1 and slightly p38 mitogen-activated protein kinases
      (MAPK), and cyclooxygenase-2 (COX-2) expression in BV-2 cells. CONCLUSION: Taken
      together, these results indicate that the protective mechanism of the GJ extract
      involves an antioxidant effect and inhibition of JNK2/1 MAP kinase and COX-2
      expressions in LPS-induced inflammation of BV-2 cells.

PMID- 26221480
TI  - Therapeutic angiogenesis promotes efficacy of human umbilical cord matrix stem
      cell transplantation in cardiac repair.
AB  - OBJECTIVES: Although previous studies have confirmed the beneficial effects of
      human umbilical cord matrix stem cell (hUCM) transplantation post myocardial
      infarction (MI), but this stem cell resource has no potential to induce
      angiogenesis. In order to achieve the process of angiogenesis and cardiomyocyte
      regeneration, two required factors for cardiac repair agents were examined
      namely; hUCM and VEGF on an infarcted heart. The main objective of this research
      is to investigate the combinatory effect of dhUCM and VEGF transplantation on an
      infarcted heart. MATERIALS AND METHODS: 45 min of ligating the left anterior
      descending coronary artery, the MI-induced animals received 50 MUl PBS, 5 MUg
      VEGF, 5*10(6) hUCM cells alone, combined with 5 MUg VEGF and 5*10(6)
      differentiated hUCM cells alone or combined with 5 MUg VEGF through
      intramyocardial injection. MI group, without hUCM and VEGF served as the control
      group. Left ventricular function and angiogenesis were also evaluated. RESULTS:
      After eight weeks post MI, there were significant rise in left ventricular
      ejection farction in dhUCM+VEGF group compared to the other treated and non
      treated groups (P<0.05). Fibrosis tissue was markedly lower in the dhUCM+VEGF and
      hUCM+VEGF groups compared to the other treated and non-treated groups (P<0.05).
      Despite these benefits, vascular density in dhUCM+VEGF group was not markedly
      different compared to VEGF and hUCM+VEGF groups. The transplanted hUCM and dhUCM
      cells survived and migrated to the infarcted area. CONCLUSION: Our findings
      demonstrated that the dhUCM cells transplantation combined with VEGF were more
      efficient on an infarcted heart.

PMID- 26221481
TI  - Development of RNA aptamers as molecular probes for HER2(+) breast cancer study
      using cell-SELEX.
AB  - OBJECTIVES: Development of molecules that specifically recognize cancer cells is
      one of the major areas in cancer research. Human epidermal growth factor receptor
      2 (HER2) is specifically expressed on the surface of breast cancer cells. HER2 is
      associated with an aggressive phenotype and poor prognosis. In this study we
      aimed to isolate RNA aptamers that specifically bind to HER2 overexpressing TUBO
      cell line. MATERIALS AND METHODS: Panel of aptamers was selected using cell-based
      systematic evolution of ligands by exponential enrichment (cell-SELEX). RESULTS:
      Binding studies showed that selected aptamers can identify TUBO cell line with
      high affinity and selectivity. Our preliminary investigation of the target of
      aptamers suggested that aptamers bind with HER2 proteins on the surface of TUBO
      cells. CONCLUSION: We believe the selected aptamers could be useful ligands for
      targeted breast cancer therapy.

PMID- 26221482
TI  - Effects of treadmill exercise training on cerebellar estrogen and estrogen
      receptors, serum estrogen, and motor coordination performance of ovariectomized
      rats.
AB  - OBJECTIVES: The present study aims at examining the motor coordination
      performance, serum and cerebellar estrogen, as well as ERbeta levels, of
      ovariectomized rats (as menopausal model) following regular exercise. MATERIALS
      AND METHODS: Ten female Sprague Dawley rats aged 12 weeks old were randomly
      divided into two groups; all of which underwent ovariectomy. The first group was
      treated with regular exercise of moderate intensity, in which the rats were
      trained to run on a treadmill for 60 min per day for 12 weeks. The second group
      served as control. Rotarod test was carried out before and after exercise
      treatment. All rats were euthanized thereafter, and blood and cerebellums of the
      rats were collected. The serum and cerebellar estrogen as well as cerebellar
      ERbeta levels were measured using ELISA assays. RESULTS: The number of falls in
      the rotarod task of the exercise group was significantly lower than that of
      control group. The cerebellar estrogen level of the exercise group was
      significantly higher than that of control group. Accordingly, there was a
      significantly negative correlation between the number of falls and cerebellar
      estrogen level in the exercise group. CONCLUSION: The present study shows that a
      lengthy period of regular exercise improves the cerebellar estrogen level and
      motor coordination performance in ovariectomized rats.

PMID- 26221483
TI  - Association study of four polymorphisms in the interleukin-7 receptor alpha gene
      with multiple sclerosis in Eastern Iran.
AB  - OBJECTIVES: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the
      central nervous system (CNS) with unknown etiology. Various genetics and
      environmental factors contribute to the pathogenesis of the disease. The
      interleukin-7 receptor alpha chain (IL-7Ra) was identified as the first non-major
      histocompatibility complex (non-MHC) MS susceptibility locus. In this study we
      are trying to find the association of IL-7Ra gene polymorphisms with MS
      susceptibility in Eastern Iran. MATERIALS AND METHODS: A case-control study was
      performed in two provinces Sistan & Baluchistan and Khorasan with 219 patients
      and 258 unrelated matched healthy controls, using PCR-RFLP method for four single
      nucleotide polymorphisms (SNPs) rs7718919, rs11567685, rs11567686 and rs6897932
      of IL-7Ra gene. RESULTS: We found a tendency toward association with genotyping
      analyses in SNP rs7718919 (P=0.048, OR=4.344, and 95% CI=0.892-21.146); also
      genotype and allele frequency in gender and MS subtype stratification were shown
      to have significant association with MS. Analysis of two provinces separately
      showed a significant difference in results of the allele and genotype
      frequencies. Moreover, haplotyping analysis showed that (GTGC) has an association
      only in the male secondary-progressive multiple sclerosis (SPMS) patients in
      comparison to the healthy controls (P=0.043, OR=0.413, and 95% CI=0.179-0.955).
      CONCLUSION: IL7-Ra could be a susceptible gene to MS within the Eastern Iran
      population especially after MS and gender stratification.

PMID- 26221484
TI  - Inhibition of janus kinase 2 by compound AG490 suppresses the proliferation of
      MDA-MB-231 cells via up-regulating SARI (suppressor of AP-1, regulated by IFN).
AB  - OBJECTIVES: The Janus kinase-signal transducers and activators of transcription
      signaling pathway (JAK/STAT pathway) play an important role in proliferation of
      breast cancer cells. Previous data showed that inhibition of STAT3 suppresses the
      growth of breast cancer cells, but the associated mechanisms are not well
      understood. This study aims to investigate the effect and associated mechanisms
      of JAK/STAT pathway inhibitor AG490 on proliferation and suppression of breast
      cancer cells. MATERIALS AND METHODS: CCK-8 assay and trypan blue exclusion assay
      were used to investigate the cytotoxicity of AG490 to MDA-MB-231 cells. Real-time
      PCR was used to detect the mRNA level of SARI (suppressor of AP-1, regulated by
      IFN). Western blot was used to analyze the protein levels of SARI, phospho-STAT3
      and total STAT3. Luciferase reporter assay was adopted to explore the mechanism
      of SARI mRNA upregulation. RESULTS: AG490 suppressed the proliferation of MDA-MB
      231 cells in a dose-dependent manner. AG490 significantly up-regulated the mRNA
      and protein levels of SARI in MDA-MB-231 cells. Knockdown of SARI obviously
      attenuated AG490-induced growth suppression effect in MDA-MB-231 cells.
      Furthermore, AG490 dramatically enhanced the transcription activity of SARI
      promoter. But the transcription activity of truncated SARI promoter, which does
      not contain STAT3 binding site, cannot be activated by AG490 treatment.
      CONCLUSION: We demonstrate in this study that AG490 suppresses the proliferation
      of MDA-MB-231 cells through transcriptional activation of SARI.

PMID- 26221485
TI  - The preventive effects of dexmedetomidine against intestinal ischemia-reperfusion
      injury in Wistar rats.
AB  - OBJECTIVES: Intestinal ischemia-reperfusion is a major problem, which may lead to
      multiorgan failure and death. The aim of this study was to evaluate the
      protective effects of dexmedetomidine on cell proliferation, antioxidant system,
      cell death, and structural integrity in intestinal injury induced by ischemia
      reperfusion in rats. MATERIALS AND METHODS: Animals were randomized into three
      groups: group A, sham-operated or control; group B, intestinal
      ischemia/reperfusion (IR); and group C, intestinal IR pretreated with 50 MUg of
      dexmedetomidine. Intestine tissue was collected from all rats 30 min after
      desufflation, and fresh frozen for histological and biochemical evaluation.
      RESULTS: The intestinal tissue of group B rats showed a significant decrease in
      the antioxidant enzyme activities. However, these enzyme activities were improved
      by the administration of dexmedetomidine. Inhibiting the protein expression of
      MCP7, PAR2, P-JAK, P-STAT1, and P-STAT3 proved the protective effect of
      dexmedetomidine. The immunohistochemical staining revealed its protective effect
      by maintaining the normal structural integrity, less caspase-3 immuno reactivity,
      and increased cell proliferation count in the intestinal tissues. CONCLUSIONS:
      Intraperitoneal injection of dexmedetomidine significantly protected intestine IR
      injury in rats by inhibiting the inflammatory response, intestinal epithelial
      apoptosis, and maintaining structural integrity of intestinal cells.

PMID- 26221486
TI  - Receptor for advanced glycation end products involved in circulating endothelial
      cells release from human coronary endothelial cells induced by C-reactive
      protein.
AB  - OBJECTIVES: This study was designed to investigate the effect of receptor for
      advanced glycation end products (RAGE), S100A12 and C-reactive protein (CRP) on
      the release of circulating endothelial cells (CECs) from human coronary artery
      endothelial cells (HCAECs). MATERIALS AND METHODS: HCAECs were cultured in
      increasing concentration of CRP (0, 12.5, 25, 50MUg/ml) or S100A12 protein (0, 4,
      10, 25MUg/ml) for 24 hr. CECs were measured by flow cytometry. Small interfering
      RNA (siRNA) was designed to decrease RAGE level. Fluorescence microscopy and real
      time quantitative polymerase chain reaction were used to assess the efficiency of
      siRNA silencing RAGE. The release of CECs from HCAECs was further evaluated by
      flow cytometry. RESULTS: CRP caused a significant increase in the release of CECs
      from HCAECs. The number of CECs increased by about 2-fold in 25 MUg/ml CRP
      treated group compared to the control group (12.22% compared to 6.82%, P=0.032).
      But S100A12 failed to increase the release of CECs from HCAECs. Blockade of RAGE
      by siRNA significantly decreased the release of CECs induced by CRP (13.22% of
      CRP group compared to 8.77% of CRP+siRNA group, P=0.017). CONCLUSION: RAGE is
      involved in the release of CECs induced by CRP, and the effect can be attenuated
      by silencing RAGE. RAGE may play an important role in endothelial dysfunction in
      cardiovascular disease. Inhibition of RAGE may be a therapeutic target for
      coronary artery lesions in Kawasaki disease.

PMID- 26221487
TI  - Evaluation of cutaneous wound healing activity of Malva sylvestris aqueous
      extract in BALB/c mice.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of Malva sylvestris
      aqueous extract on cutaneous wound healing in BALB/c mice. MATERIALS AND METHODS:
      Twenty seven male BALB/c mice (2.5 months of age) were used. A cut wound
      (superficial fascia depth) was made locally. The mice were then divided into
      three groups: the first, second and third groups received topical administration
      of M. sylvestris 1% aqueous extract, silver sulfadiazine topical cream and cold
      cream (positive and negative control groups), respectively. On days 4, 7 and 10
      excisional biopsies were performed and wound healing was evaluated
      histopathologically. The data were analyzed by the ANOVA and Tukey statistical
      tests. RESULTS: On days 4 and 7, the numbers of inflammatory cells in the silver
      sulfadiazine and M. sylvestris-treated groups were significantly lower than the
      control group and keratinization at the edges of the wound in both groups was
      significantly higher than the control group. On the tenth day of the study, the
      Malva-treated mice showed better healing features and less fibrosis and scar
      formation, and also fewer hair follicles were damaged in this group. On the tenth
      day of the study, the numbers of inflammatory cells in M. sylvestris and silver
      sulfadiazine-treated groups were significantly lower than the control group.
      CONCLUSION: The present study supports the beneficial effects of M. sylvestris on
      the wound healing process and suggests a potential clinical application.

PMID- 26221488
TI  - Association between mutations in gyrA and parC genes of Acinetobacter baumannii
      clinical isolates and ciprofloxacin resistance.
AB  - OBJECTIVES: We investigated the contribution of gyrA and parC mutational
      mechanism in decreased ciprofloxacin susceptibility of Acinetobacter baumannii
      isolated from burn wound infections. MATERIALS AND METHODS: Ciprofloxacin
      susceptibility of 50 A. baumannii isolates was evaluated by disk diffusion and
      agar dilution methods. PCR and sequencing were performed for detection of
      mutation in gyrA and parC genes. RESULTS: The 44 and 4 isolates of A. baumannii
      exhibited full and intermediate-resistant to ciprofloxacin, respectively.
      Overall, the 42 isolates with double mutations of gyrA and parC genes showed a
      higher level of ciprofloxacin resistance than the 3 isolates with single
      mutations of gyrA or parC. CONCLUSION: Simultaneous mutations in gyrA and parC
      genes are expected to play a major role in high-level fluoroquinolone resistance
      in A. baumannii; albeit a single mutation in DNA topoisomerase IV could
      occasionally be associated with intermediate-resistance to these antimicrobials.

PMID- 26221489
TI  - Muco-bioadhesive containing ginger officinal e extract in the management of
      recurrent aphthous stomatitis: A randomized clinical study.
AB  - BACKGROUND: Recurrent aphthous stomatitis (RAS) is the most common oral mucosal
      lesions in the general population. Various treatment modalities have been used;
      but no specific therapy proved to be definitive. Ginger Officinale (ginger)
      indicated to have anti-inflammatory properties in herbal medicine. Thus, this
      study aimed to evaluate the efficacy of ginger containing bioadhesive in the
      treatment of aphthous ulcers. METHODS: In this randomized double-blind placebo
      controlled trial, 15 patients were enrolled. The clinical efficacy of the
      mucoadhessive on pain, inflammatory zone and ulcer's diameter in the test period
      was compared with that of the base treatment and no treatment periods during 10
      days of study. RESULTS: Significant reduction in pain was observed on day 5
      between placebo (using base bioadhesives) and without treatment periods at the
      first phase of the study (4.53 vs. 3.27; P=0.038. ( Reduction in inflamed halo
      diameters was significant on day 1 between without treatment and ginger
      containing bioadhesives )46.73 vs 28.67; P=0.044). Other variables such as the
      diameter of ulcers did not indicate any significant differences in both periods.
      CONCLUSION: This study indicated that ginger bioadhesive is capable to relieve
      pain of RAS. However, its efficacy on ulcer diameter, inflamed halo and healing
      time was not significantly different compared to the results of the placebo
      received period.

PMID- 26221490
TI  - Human papilloma virus infection in non-cancerous versus normal esophageal tissue
      samples by endoscopy.
AB  - BACKGROUND: Cancers are the second most common cause of non-accidental deaths in
      Iran, after cardiovascular mortality. Although most cases of esophageal squamous
      cell carcinoma (ESCC) in the USA and western populations have been attributed to
      high levels of exposure to tobacco and alcohol, but in Iranian populations, other
      risk factors especially infectious agents have been postulated as possible
      causes, particularly human papillomavirus (HPV). This study aimed to determine
      the prevalence and the types of HPV infection in biopsy samples taken from non
      cancerous esophageal lesions during upper endoscopy. METHODS: A total of 80 non
      cancerous esophageal samples were collected in parafinnated blocks of tissue
      archives in pathology. After DNA extraction, qualitative PCR (qPCR) was performed
      using the HPV L1 primer pairs MY09/MY11 and then genotyping was performed in HPV
      DNA positive by Real time PCR. RESULTS: From 80 cases, 29 (36.3%) were qPCR
      positive. Using the Real-time PCR method, a total of 14 HPV genotypes were
      assessed. We detected HPV-11 as a dominant type in this study and we did not find
      any type of HPV-16 and 18 genotypes. CONCLUSION: In this study, HPV-II was the
      most common type in esophageal samples, in contrast we have found no oncogenic
      HPV like HPV 16 and 18 which are the most known responsible factors of ESCC in
      other countries.

PMID- 26221491
TI  - Sedation with etomidate-fentanyl versus propofol-fentanyl in colonoscopies: A
      prospective randomized study.
AB  - BACKGROUND: The combination of propofol-fentanyl for sedation during colonoscopy
      is characterized by high prevalence of side effects. Etomidate-fentanyl provides
      fewer hemodynamic and respiratory complications. The aim of our study was to
      compare the safety and efficacy of propofol-fentanyl and etomidate-fentanyl for
      conscious sedation in elective colonoscopy. METHODS: This double-blind clinical
      trial was conducted on 90 patients aged between 18- 55 years old who were
      candidates for elective colonoscopy. Patients were randomized to receive sedation
      with fentanyl plus propofol or etomidate. Two minutes after injecting 1 micro/kg
      of fentanyl, the patients received 0.5mg/kg propofol by infusion (25 u/kg/min) or
      0.1 mg/kg etmoidate (15 u/kg/min). Pulse rate, mean arterial blood pressure,
      respiratory rate, and saturation of peripheral oxygen (SPO2) were monitored. In
      addition, the patient and colonoscopist satisfaction, the recovery time, sedation
      and pain score in both groups were assessed. RESULTS: Sedation score in propofol
      group was higher. Pain score as well as the physician and patient satisfaction
      showed no significant difference between the two study groups. Hemodynamic
      changes and arterial saturation were the same in both groups. The duration of
      recovery was 1.27+/-0.82 minutes in the etomidate group; versus 2.57+/-2.46
      minutes in the propofol group (P=0.001). Recovery time in the etmoid group was
      2.68+/-3.14 minutes and in the propofol group was 5.53+/-4.67 minutes (p=0.001).
      CONCLUSION: The combination of fentanyl and etomidate provides an acceptable
      alternative to sedation with fentanyl and propofol with the advantage of
      significantly faster recovery time, in the outpatient setting.

PMID- 26221492
TI  - Validation of the Persian version of the inflammatory bowel disease questionnaire
      (IBDQ) in ulcerative colitis patients.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) are a group of inflammatory
      conditions of the colon and small intestine that may have critical consequences
      on patient's quality of life (QOL). Many disease-specific QOL tools have been
      developed recently. The McMaster Inflammatory Bowel Disease Questionnaire (IBDQ)
      is one of them. The aim of this study was to translate the IBDQ from English to
      Persian and evaluate the validity and reliability of this version of the McMaster
      IBDQ. METHODS: 68 subjects with ulcerative colitis were recruited in this study.
      The original IBDQ was translated into Persian using back- translation method. The
      reliability of the subscales and the summary score of the Persian IBDQ was
      demonstrated by intraclass correlation coefficients, their validity was evaluated
      by their correlations with SF-36, visual analogue scale and colitis activity
      index. RESULTS: All dimensions of IBDQ met the standards of construct validity
      and were correlated well with SF-36, visual analog scale and colitis activity
      index. IBDQ was able to discriminate the different groups of patients. The
      intraclass correlation coefficient was very high and its value was close to one
      (P<0.05). All dimensional scores differed significantly between the baseline and
      the follow-up measurement. CONCLUSION: The findings of this study conclude that
      the Persian translation of IBDQ confers satisfactory psychometric and cultural
      properties when applied to a sample of Iranian population with inflammatory bowel
      disease. This questionnaire is recommended for use in clinical trials and in the
      assessment of efficacy of interventions and therapy.

PMID- 26221493
TI  - Evaluation of oxidative stress in endometriosis: A case-control study.
AB  - BACKGROUND: Recent studies have suggested that oxidative stress (OS) may have a
      contribution in the pathogenesis of endometriosis. However, the results of
      previous studies regarding OS in endometriosis are controversial. The objective
      of this study was to compare the serum levels of OS markers in endometriosis
      versus the control group. METHODS: This case-control study was carried out on 30
      women with endometriosis aged 20-38 years presented to Fatemeh Zahra Infertility
      and Reproductive Health Research Center, Babol, Iran between March 2011 through
      November 2013. The serum samples of 40 women with same age were collected as the
      control group. The serum levels of malondialdehyde (MDA), carbonyl and iron were
      measured by photometric methods and compared between the patient and control
      groups using t-test. Also, we used ROC curve analysis to determine the
      discrimination ability of these markers. RESULTS: Serum iron in endometriosis
      patients was significantly higher than control (p<0.0001). Area under the ROC
      curve (AUC) for iron, MDA and carbonyl were 0.899, 0.648 and 0.530, respectively.
      Serum iron at cutoff value of 173.3 ug/dl exhibited high discrimination ability
      to discriminate endometriosis from control. CONCLUSION: These findings indicate
      that the high level of serum iron may promote OS in patients with endometriosis.
      In addition, serum Iron at cut off level of 173.3 exhibits high discriminative
      ability to distinguish patients with endometriosis from healthy subjects.

PMID- 26221494
TI  - Influence of splenectomy on immunoglobulins and complement components in major
      thalassemia.
AB  - BACKGROUND: Thalassemia is the most common anemia with hereditary base in Iran.
      The aim of this study was to evaluate the humoral immune system and assess the
      effect of splenectomy on the serum level of immunoglobulins IgG, IgM, and IgG and
      complement components in patients with major thalassemia. METHODS: This quasi
      experimental study (before-after) was performed on 40 patients with major
      thalassemia that referred to the treatment centers of Babol for splenectomy from
      March 2011 to March 2013. RESULTS: The mean age of patients under study was
      25.38+/-6.89 years. The results of this study showed that the rate of IgA and IgM
      had a significant decrease after splenectomy. However, the increase of serum
      level in IgG in this study was not significant. The serum levels of C3 and CH50
      were evaluated in all patients that its reduction was statistically significant,
      but the decrease of serum levels in C4 was not significant. CONCLUSION: The
      spleen plays a role in releasing immunoglobulins and starter proteins of
      complement activation pathways and splenectomy causes reduction in the serum
      levels of immunoglobulins and complement components.

PMID- 26221495
TI  - Minimal inhibitory concentration of microorganisms causing surgical site
      infection in referral hospitals in North of Iran, 2011-2012.
AB  - BACKGROUND: A surgical site infection (SSI) is the most common nosocomial
      infection after surgery and is the third most common infection in hospitalized
      patients. The aim of this study was to asses minimum inhibitory concentration
      (MIC) of the causing agents of SSI and antimicrobial susceptibility patterns.
      METHODS: This cross-sectional study was done in three referral hospitals in North
      of Iran during 2011-2012. The samples were taken one month after orthopedic,
      abdominal, cesarean section surgery and coronary artery bypass graft (CABG) in
      patients with scores compatible to SSIs criteria. The sample was sent for
      bacteriologic culture and MIC determination for positive cases by broth
      microdilution method. The data were collected and analyzed. RESULTS: From 103
      positive cases S. aureus, E.coli and coagulase negative staphylococci were the
      most common isolated agents as 29.12%, 23.3% and 21.3%, respectively. S. aureus
      was sensitive to vancomycin (70%), amikacin (70%) and teicoplanin (76.6%) and
      cogulase negative staphylococci was sensitive to vancomycin (68.1%) and
      teicoplanin (72.6%) and E.coli to amikacin (95.83%) and imipenem and meropenem
      (66.66%). P.aeroginosa showed no sensitivity to cefepime and was sensitive to
      imipenem (93.75%) and meropenem (81.25%). CONCLUSION: The most important point is
      worrisome problem of the increased MIC of S. aureus to vancomycin that causes
      difficult use in the treatment of staphylococcal SSIs. In spite of resistance of
      micro-organisms to cephalosporins, gram negative organisms had low MIC to
      carbapenemes especially P.aeroginosa although the rate of its MIC is increasing.

PMID- 26221496
TI  - Association of staphylococcus cohnii subspecies urealyticum infection with
      recurrence of renal staghorn stone.
AB  - BACKGROUND: Stphylococcus cohnii is an organism of coagulase negative species
      which is considered as normal flora. However, it has been isolated from urinary
      tract infections and surgical prostheses but its relation with staghorn stones
      has not been reported, yet. CASE PRESENTATION: A 50-years-old woman presented
      with left renal staghorn stone in June 2014. She had bilateral staghorn stones 7
      years ago. Staphylococcus cohnii subspecies urealyticum were detected from a
      removed stone. After 7 years, recurrence staghorn stone in her left kidney was
      diagnosed and patient underwent another surgery. The patient had several attacks
      of cystitis during these 7 years. The results of stone and urine cultures
      revealed staphylococcus cohnii subspecies urealyticum. CONCLUSION: This case
      report emphasizes a possible association between staphylococcus cohnii subspecies
      urealyticum infection and recurrence renal staghhorn stone.

PMID- 26221497
TI  - A case of Brugada Syndrome unmasked by a postoperative febrile state.
AB  - BACKGROUND: Brugada Syndrome (BS) is an inherited ion channelopathy characterized
      by an electrocardiographic (ECG) pattern of a coved type ST segment elevation in
      right precordial leads with or without right bundle branch block. CASE
      PRESENTATION: A 23-year old male presented with right lower quadrant abdominal
      pain. Further evaluation revealed a diagnosis of acute appendicitis. The patient
      developed a febrile episode on second post-operative day of laparoscopic
      appendectomy. ECG revealed features consistent with BS. Prompt control of
      temperature in the patient resolved the ST-segment elevation and prevented
      potentially life-threatening arrhythmias. CONCLUSION: Febrile episodes in
      susceptible patients may unmask a concealed BS. Prompt control of temperature is
      advocated to reduce the risk of life-threatening arrythmias.

PMID- 26221498
TI  - Human brucellosis: An overview.

PMID- 26221499
TI  - Helicobacter pylori infection and osteoporosis in elderly patients.

PMID- 26221500
TI  - Metabolic syndrome and its associated risk factors in Iranian adults: A
      systematic review.
AB  - BACKGROUND: Metabolic syndrome (MetS) is a complex clustering cardiovascular risk
      factors such as abdominal obesity, hypertension, diabetes and dylipedemia. It has
      been a growing health problem in Iranian adults in recent decade. The objective
      of this article was to review the prevalence of MetS and the corresponding risk
      factors among Iranian adults. METHODS: We conducted a systematic review to
      extract the published articles regarding metabolic syndrome and its risk factors
      among Iranian adults aged >19 years by searching in PubMed, Google Scholar, SID,
      Magiran and Iranmedex databases. The forty-three published articles were selected
      regarding MetS among Iranian adults in this review during 2005-2014. RESULTS:
      From the 43 studies, the rate of MetS varied from 10% to 60% depending on sex,
      age and region. The highest rate reported among postmenopausal women in Shiraz
      was over 60%. There was almost a consistent finding that the rate of MetS was
      higher among women compared with men across national level except in one study. A
      very sharp difference (43.3% vs. 17.1%) was observed in western Iran (Kordestan
      province) between sexes. MetS was significantly more prevalent among older
      adults, postmenopausal women, less-educated people, those living in urban areas
      and those with low physical activity and unhealthy eating habits across national
      level consistently. CONCLUSION: An emerging high rate of MetS across national
      level highlights the lifestyle modification as preventive measures in Iranian
      population by focusing primarily on high risk profiles such as low socioeconomic
      background, low level of education, older age and postmenopausal women.

PMID- 26221501
TI  - Relationship between Helicobacter pylori infection (HP) and bone mineral density
      (BMD) in elderly people.
AB  - BACKGROUND: Low bone mass is a frequent complication of chronic inflammatory
      disease. The pathogenesis of osteoporosis in chronic inflammatory disease may be
      secondary to releases of cytokines such as TNF- and IL6. Chronic gastritis due to
      helicobacter pylori (HP) infection may lead to decreased bone mineral density
      (BMD) and predispose patients to osteoporosis. The objective of this study was to
      determine the BMD status in HP positive patients with gastritis versus HP
      negative cases. METHODS: In this cross-sectional study, we enrolled 967
      participants aged 60 years old and more from Amirkola Health Study Ageing
      Project. Seven-hundred and fifty eight HP positive and 209 HP negative patients
      were analyzed. BMD was measured by dual-energy x-ray absorptiometry (DXA) method
      in the spine and femoral neck in all participants. RESULTS: The mean age in HP+
      and HP- negative patients was 68.3+/-6.8 and 69.3+/-7.4 years, respectively. BMD
      g/cm2 in the spine and femoral neck did not differ between the two groups (P=0.19
      and 0.22 respectively). The prevalence of osteoporosis did not also differ across
      the two groups as well. There was no relationship between the level of antibodies
      against HP and BMD. CONCLUSION: According to the findings of this study, H.
      pylori infection is not associated with BMD changes in the elderly population.

PMID- 26221502
TI  - Women's satisfaction in early versus delayed postcaesarean feeding: A one-blind
      randomized controlled trial study.
AB  - BACKGROUND: The early postoperative feeding after caesarean section (C- section)
      has remained controversial. This study was designed to evaluate the safety and
      efficacy of early versus delayed postcaesarean section oral feeding regarding
      gastrointestinal complications and patients postoperative satisfaction after C-
      section. METHODS: This clinical trial study was conducted on 200 pregnant women
      undergoing planned C-section under spinal anesthesia (Registration Number: IRCT:
      138712211760N1). Women were randomly divided in two groups; group A (early
      feeding group) comprised of 101 patients who were encouraged to take oral fluid.
      If they tolerated, they continue semi-solid and solid foods starting 2 h after
      caesarean section. Group B (delayed feeding group) comprised of 99 patients who
      were given oral fluid 8 h after surgery. After beginning of feeding the patients'
      tolerance, first flatus, first defecation, beginning of regular diet, the length
      of hospital stay and also patient satisfaction level were evaluated in each group
      by visual scale analog (VAS). RESULTS: The mean time of the first passage of
      flatus was 10.2+/-1.7 hours for the early oral feeding group versus 10.7+/-1.6
      hours for the delayed feeding group and the difference was significant (P=0.03).
      Duration to first defecation and length of hospital stay as well as patient
      satisfaction level did not differ significantly between the two groups.
      CONCLUSION: The results of this study suggest early postcaesarean feeding. It is
      well tolerated and helps return normal feeding habits.

PMID- 26221503
TI  - Influence of thyroidectomy on postoperative serum calcium level regarding serum
      vitamin D status. A prospective study.
AB  - BACKGROUND: Hypocalcemia is a well-recognized complication after total
      thyroidectomy. Hypovitaminosis D may have additional effect in the development of
      hypocalcemia. This study aimed to determine the effect of total thyroidectomy on
      postoperative serum calcium in patients with and without hypovitaminosis D.
      METHODS: This prospective study was performed on patients who underwent total
      thyroidectomy from 2011 to 2014 in Imam Khomeini General Hospital of Mazandaran
      University of Medical Sciences. Serum calcium and vitamin D values were recorded
      before and after surgery. The patients were classified according to serum vitamin
      D concentrations as less 10 ng/ml (vitamin D deficiency) or higher (control
      group). The mean values of postoperative calcium level for each class of serum
      vitamin D were determined and compared. Hypocalcemia was defined as a
      postoperative calcium level <8 mg/dl. RESULTS: 125 patients due to thyroid
      disease underwent total thyroidectomy. The incidence of symptomatic and
      asymptomatic hypocalcemia after surgery was 12% (n=15) and 3.2% (n=4)
      respectively. 82 (65.6%) patients had vitamin D deficiency and 43 (34.4%)
      patients had sufficient vitamin D level. There was not any significant difference
      in calcium level (8.67+/-0.58 mg/dl vs. 8.70+/-0.59 mg/dl) between two vitamin D
      studied groups after thyroid surgery (p>0.05). CONCLUSION: The findings of this
      study indicated that vitamin D deficiency had no significant effect on post
      thyroidectomy serum calcium level.

PMID- 26221504
TI  - Determination of serum lipid profile in patients with diabetic macular edema that
      referred to Shahid Beheshti and Ayatollah Rouhani Hospitals, Babol during 2011
      2012.
AB  - BACKGROUND: Diabetes is a common metabolic disorder leading to the development of
      many complications, among which diabetic retinopathy and macular edema are the
      most significant. These complications can contribute to blindness if not
      diagnosed or treated properly, and several studies have been conducted to
      evaluate the methods for the prevention or slowing down their progression.
      Therefore, serum lipids, apparently play an effective role in the creation and
      acceleration of macular edema, we therefore determined the relationship of serum
      lipid level in patients with diabetic macular edema in the present study.
      METHODS: 180 participants were selected from patients with the definite diagnosis
      of diabetes referred to the eye clinic of Shahid Beheshti and Ayatollah Rouhani
      Hospitals of Babol during 2011-2012, the patients with a history of taking lipid 
      lowering drugs and hypertension were excluded from the study. The study data were
      provided from the medical records of each patients. SPSS Version 18 was used for
      analyses. RESULTS: In the present investigation, the mean age of participants was
      53.22+/-with the age range of 18-77 years. Ninety patients with diabetic
      retinopathy and macular edema were compared with ninety patients with diabetic
      retinopathy without macular edema (control group) were compared. There was a
      significant difference in serum cholesterol and LDL-cholesterol between patients
      and groups (p<0.000). CONCLUSION: The results of this study indicate that high
      serum cholesterol and LDL-cholesterol is associated with severity of diabetic
      retinopathy particularly with macular edema.

PMID- 26221506
TI  - Comparison of the analgesic effect of intravenous paracetamol/midazolam and
      fentanyl in preparation of patients for colonoscopy: A double blind randomized
      clinical trial.
AB  - BACKGROUND: Although some patients can tolerate colonoscopy procedure using
      fentanyl/ midazolam without any sedation and analgesic requirements but some
      patients may require additional sedation with benzodiazepines. We performed the
      present study to compare the effect of paracetamol/midazolam with fentanyl/
      midazolam. METHODS: In a clinical trial, 96 patients aged 18 to 75 years old, who
      were candidate for elective colonoscopy assigned consecutively into two groups as
      paracetamol/midazolam and fentanyl/midazolam. The first group received 1 gr
      paracetamol 45 minutes before colonoscopy and 0.5 mg/kg midazolam 5 minutes
      before colonoscopy whereas the second group received 04- 0.5-1 mcg/kg fentanyl 3
      minutes before colonoscopy and similar dose of midazolam. The two groups were
      compared in regard to patient intensity, discomfort, acolonoscopist and, patient
      satisfaction and rescue dose of propofol during colonoscopy and vital signs.
      RESULTS: There was no significant difference between the two groups for patient
      pain score, colonoscopist satisfaction, patient satisfaction and rescue dose of
      propofol (P=0.817, 0.978, 0.460, and 0.104, respectively). The incidence of apnea
      was greater in fentanyl group (P=0.045). After adjusting for age and education,
      there was also no significant difference between the two groups. CONCLUSION: This
      study indicates that paracetamol can be considered as an alternative drug regimen
      in preparation of colonoscopy.

PMID- 26221505
TI  - Age distribution types of bladder cancers and their relationship with opium
      consumption and smoking.
AB  - BACKGROUND: Recognition of the predisposing factors of bladder cancer is very
      important and provides possible prevention measures. The aim of this study was to
      investigate the types, distribution of bladder tumors and their relationship with
      opium consumption and smoking in patients who referred to Shahid Beheshti
      Hospital, Babol, Iran. METHODS: In this case-control study, all patients
      diagnosed with bladder cancer who underwent surgery during 2001-2012 were
      enrolled. The subjects of the control group were selected among the patients who
      underwent ERCP (endoscopic retrograde cholangiopancreatography) for gallstone and
      had no tumors and genitourinary problems. Data regarding demographic, pathology
      reports and tumor type, smoking status, history of opium consumption and its
      duration were collected. Patients and controls were compared using t-test and chi
      square test. SPSS software Version 20 was used for analysis. RESULTS: In this
      study, 175 patients with an average age of 63.30+/-15.29 years and 175 age-
      matched controls were studied. A significant association was observed between
      smoking and opium consumption with bladder cancer (P=0.001 for both). CONCLUSION:
      The results of this study showed that opium consumption and smoking are
      associated with bladder cancer.

PMID- 26221507
TI  - Vitamin D status and distribution in patients with chronic obstructive pulmonary
      disease versus healthy controls.
AB  - BACKGROUND: Vitamin D has a potential to modulate inflammatory response against
      noxious particles in patients with chronic obstructive pulmonary disease (COPD).
      The present study was conducted to determine the status of serum vitamin D in
      COPD versus healthy group. METHODS: The patients presented to the outpatient
      pulmonary clinic of Ayatollah Rouhani Hospital, Babol Iran. Diagnosis of COPD was
      confirmed based on airflow limitation defined as FEV1/FVC ratio <70% and FEV1<
      80% of predicted. All eligible patients aged >= 40 years old entered the study.
      Pulmonary infection, tuberculosis, pleural effusion, congestive heart failure,
      pulmonary hypertension and embolism, restrictive airway disease, conditions
      leading changes in vitamin D metabolism and absorption were excluded. Serum 25
      hydroxyvitamin D (25-OHD) was determined by electrocheminluminescence method and
      levels <20, 20-29, and >=30ng/ml were considered as deficiency, insufficiency,
      and sufficiency. In statistical analysis, the frequency of serum 25-OHD
      deficiency and insufficiency in patients were compared regarding age of <= 50 or
      >50 years old. All patients were males and age and sex-matched controls were
      selected among healthy subjects accompanied COPD patients. RESULTS: Ninety
      patients and 100 controls with respective mean (+/-SD) age of 64.8+/-11.7 and
      62.6+/-11.7 years old (P=0.19) were studied. Compared with control, proportions
      of serum 25-OHD deficiency and insufficiency in patients >50 years were higher
      and deficiency was lower (61.5% vs 87.5%, P=0.11). CONCLUSION: These findings
      indicate that a significant proportion of young COPD patients have insufficient
      serum 25-OHD. Regarding a positive relationship between 25-OHD and FEV1 in COPD,
      these findings highlight serum 25-OHD assessment in COPD for recognizing high
      risk patients.

PMID- 26221508
TI  - Influence of core stability exercise on lumbar vertebral instability in patients
      presented with chronic low back pain: A randomized clinical trial.
AB  - BACKGROUND: Excessive lumbar vertebrae translation and rotation in sagittal plane
      has been attributed as an associated factor of lumbar segmental instability (LSI)
      and low back pain (LBP). Reduction of these abnormalities improves back pain. The
      aim of this study was to investigate the effect of core stability exercise on the
      translation and rotation of lumbar vertebrae in sagittal plane in patients with
      nonspecific chronic LBP (NSCLBP). METHODS: In this randomized clinical trial, 30
      patients with NSCLBP due to LSI were included. The participants were randomly
      divided into two groups of treatment and control. The treatment group received
      general exercises plus core stability exercise for 8 weeks whereas; the control
      group received only general exercises. The magnitude of translation (mm) and
      rotation (deg) of lumbar vertebrae in the sagittal plane was determined by
      radiography in flexion and extension at baseline and after intervention. The
      primary outcome measures were to determine the mean changes from baseline in
      translation and rotation of the lumbar vertebrae in the sagittal plane after 8
      weeks of intervention in each group. The secondary outcome was to compare the two
      groups in regard to translation and rotation of the lumbar vertebrae at the end
      of the study period. Data were analyzed using paired t-test and independent t
      test. RESULTS: Thirty patients aged 18-40 years old with clinical diagnosis of
      NSCLBP entered the study. Compared with baseline values, mean value of
      translation and rotation of the lumbar vertebra reduced significantly in both
      groups (P<0.05), except L3 translation in the control group. At the endpoint,
      mean translation value of L4 (P=0.04) and L5 (P=0.001) and rotation of the L5
      (P=0.01) in the treatment group was significantly lower than the control group.
      CONCLUSION: These findings indicate that in patients presented with NSCLBP due to
      lumbar segmental instability, core stability exercises plus general exercises are
      more efficient than general exercises alone in the improvement of excessive
      lumbar vertebrae translation and rotation.

PMID- 26221509
TI  - Immunohistochemical expression of CD10 in cutaneous basal and squamous cell
      carcinomas.
AB  - BACKGROUND: Non-melanoma skin cancer is the most common malignant tumor in
      humans. The role of ultraviolet radiation is well-known in the pathogenesis of
      basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). CD10 is a zinc
      dependent metallopeptidase known as common acute lymphoblastic leukemia antigen
      (CALLA). Although CD10 expression has been investigated in some cutaneous tumors,
      to our knowledge, data regarding its expression in cutaneous epithelial neoplasms
      are very limited. In this study, we aimed to determine the immunohistochemical
      expression of CD10 in BCC and SCC and to find whether it could distinguish
      between these two skin malignancies. METHODS: Twenty SCC and 42 BCC cases were
      retrieved randomly from Ayatollah Rouhani Hospital pathology archive and CD10
      expression was determined in tumoral and stromal cells of each case based on
      immunohistochemical method. Positive CD10 staining was identified as brown
      cytoplasmic, with or without cell membrane staining. RESULTS: In all the 20 SCC
      cases, tumor cells failed to stain with CD10 in contrast to the stromal cells
      that showed CD10 expression in 18 cases (90%). In BCC cases, the expression of
      CD10 was noted in tumor cells in 25 cases (59.5%) and in stromal cells of 32
      cases (76.2%). There was no relation between CD10 expression in aggressive and
      non- aggressive BCC. CONCLUSION: Our findings suggest that CD10 is a useful
      immunohistochemical marker to differentiate between BCC and SCC. At least, if
      tumor cells were CD10 positive, this would favor BCC over SCC. Due to small
      number of aggressive BCC in contrast to non- aggressive types, more studies need
      to be done to prove or rule out this finding.

PMID- 26221510
TI  - Clinical presentation of coronary arteriovenous fistula according to age and
      anatomic orientation.
AB  - BACKGROUND: Coronary arteriovenous fistulas (CAVFs) are direct connections from
      one or more coronary arteries to cardiac chambers or a large vessel. They are
      mostly of congenital origin. The aim of this study was to describe clinical
      presentation and also delineate the course and management of CAVF. METHODS:
      Clinical data, chest x-rays, echocardiographic and angiographic evaluation of 40
      patients with congenital CAVF during 1990 to 2008 were reviewed retrospectively.
      RESULTS: Seventeen patients were <= 20 years old (42.5%) were mostly
      asymptomatic, and twenty tree cases were older than 20 years old (57.5%), mostly
      symptomatic (P<0.05). Twenty one (52.5%) patients had pure CAVF and nineteen
      (47.5%) patients with associated intarcardiac congenital heart disease (15%) or
      acquired valvular and coronary arteries diseases (32.5%). CAVFs mostly originated
      from left anterior descending artery (LAD) (42.5%) and mostly drained into the
      main pulmonary artery (MPA) (35 %). Twenty-four patients underwent CAVF surgical
      ligation. From twenty-one patients with pure CAVF, eight (38%) patients were
      complicated by congestive heart failure and aneurism formation of fistula.
      CONCLUSION: Unlike some previous reports, in our study, the most prevalent origin
      site for CAVFs was the left anterior descending (LAD). Most patients with CAVFs
      especially those who went first diagnosed before 20 years old were asymptomatic.
      On the other hand, as the continuous murmur is not always detected in children or
      infants, consequently, cases of spontaneous closure may remain undetected. All
      symptomatic and asymptomatic patients with moderate to severe shunting should be
      operated on and minimal morbidity and good surgical results could be expected.

PMID- 26221511
TI  - The effect of resveratrol on the expression of MDR1 gene in leukemic
      lymphoblast's of acute lymphoblastic leukemia patients.
AB  - BACKGROUND: Chemotherapy plays a very important role in the treatment of leukemia
      but the resistance properties of the lymphoblasts limit the effect of
      chemotherapy. One of the main mechanisms of resistance to chemotherapy is the
      increased expression of MDR1 gene. The aim of this study was to explore the
      effect of resveratrol on the expression of MDR1 gene in leukemic lymphoblast of
      new cases of acute lymphoblastic leukemia (ALL) patients in vitro. METHODS:
      Separation of lymphoblasts of 5 new case ALL patients from peripheral blood was
      performed by ficoll density gradient centrifugation. Lymphoblasts were cultured
      in RPMI 1640 medium. Lymphoblasts were treated with 50umol/L resveratrol for 48
      h. Total RNA was extracted with guanidine isothiocyanate. RNA was converted to
      cDNA. Real time PCR was used to detect mRNA expression of MDR1. RESULTS: The
      results of gene detection showed that the expression of MDR1 did not change
      significantly in the patients however, in one patient expression of MDR1
      increased upon treatment with resveratrol. CONCLUSION: The results of this study
      did not support resveratrol as a compound to reverse multidrug resistance in
      leukemic lymphoblasts.

PMID- 26221512
TI  - Prevalence of influenza A/H3N2 virus in northern Iran from 2011 to 2013.
AB  - BACKGROUND: Influenza A virus is the most virulent human pathogen and causes the
      most serious problem. Having epidemiological knowledge about this disease is
      important. The aim of this study was to determine the prevalence of influenza
      A/H3N2 virus infection in northern Iran from 2011 to 2013 using the real-time
      polymerase chain reaction (RT-PCR). METHODS: In this cross-sectional study 57
      samples were collected from patients with influenza-like illness (T>= 38  degrees
      C and cough or sore throat. Influenza-RNA was extracted from the samples using
      PureLink(TM) Viral RNA/DNA Kit. RT-PCR was one using SuperScript III Platinum,
      Quantitive Real Time PCR system from invitrogen with a specific type of primers
      and probs. All samples were examined in the Influenza laboratory of Mazandaran
      University of Medical Sciences. RESULTS: The mean age of patients was 38.2+/-14.5
      year, 278 (48.69%) were males and 293 (51.31%) females. A total number of 201
      patients (35.2%) were diagnosed as influenza A1 H3 N2 infection. CONCLUSION: The
      results show that the prevalence of A/H3N2 in the North of Iran is considerable
      and needs more attention for preventive measures.

PMID- 26221513
TI  - Branched-chain amino acids and the association with type 2 diabetes.

PMID- 26221515
TI  - Corneal confocal microscopy: Recent progress in the evaluation of diabetic
      neuropathy.
AB  - The present brief review discusses recent progress with corneal confocal
      microscopy for the evaluation of diabetic sensorimotor polyneuropathy. Corneal
      confocal microscopy is a new, non-invasive and reproducible diagnostic modality,
      and it can also be easily applied for patient follow up. It enables new
      perspectives of studying the natural history of diabetic sensorimotor
      polyneuropathy, severity of nerve fiber pathology and documenting early nerve
      fiber regeneration after therapeutic intervention. It shows moderate to high
      sensitivity and specificity for the timely diagnosis of diabetic sensorimotor
      polyneuropathy. Currently, corneal confocal microscopy is mainly used in
      specialized centers, but deserves more widespread application for the assessment
      of diabetic sensorimotor polyneuropathy. Finally, further progress is required in
      terms of technical improvements for automated nerve fiber quantification and for
      analysis of larger images. 

PMID- 26221516
TI  - High-throughput screening of small interfering ribonucleic acid identifies
      important modulators in islet dysfunction and apoptosis.

PMID- 26221514
TI  - Photoreceptors in diabetic retinopathy.
AB  - Although photoreceptors account for most of the mass and metabolic activity of
      the retina, their role in the pathogenesis of diabetic retinopathy has been
      largely overlooked. Recent studies suggest that photoreceptors might play a
      critical role in the diabetes-induced degeneration of retinal capillaries, and
      thus can no longer be ignored. The present review summarizes diabetes-induced
      alterations in photoreceptor structure and function, and provides a rationale for
      further study of a role of photoreceptors in the pathogenesis of the retinopathy.

PMID- 26221517
TI  - Quo vadis: Where have the beta-cells gone?

PMID- 26221518
TI  - Effects of chromium malate on glycometabolism, glycometabolism-related enzyme
      levels and lipid metabolism in type 2 diabetic rats: A dose-response and curative
      effects study.
AB  - AIMS/INTRODUCTION: The present study was designed to evaluate the effect of
      chromium malate on glycometabolism, glycometabolism-related enzyme levels and
      lipid metabolism in type 2 diabetic rats, and dose-response and curative effects.
      MATERIALS AND METHODS: The model of type 2 diabetes rats was developed, and daily
      treatment with chromium malate was given for 4 weeks. A rat enzyme-linked
      immunosorbent assay kit was used to assay glycometabolism, glycometabolism
      related enzyme levels and lipid metabolism changes. RESULTS: The results showed
      that the antihyperglycemic activity increased with administration of chromium
      malate in a dose-dependent manner. The serum insulin level, insulin resistance
      index and C-peptide level of the chromium malate groups at a dose of 17.5, 20.0
      and 20.8 MUg chromium/kg bodyweight were significantly lower than that of the
      model, chromium trichloride and chromium picolinate groups. The hepatic glycogen,
      glucose-6-phosphate dehydrogenase and glucokinase levels of the chromium malate
      groups at a dose of 17.5, 20.0 and 20.8 MUg chromium/kg bodyweight were
      significantly higher than that of the model, chromium trichloride and chromium
      picolinate groups. Chromium malate at a dose of 20.0 and 20.8 MUg chromium/kg
      bodyweight significantly changed the total cholesterol, low-density lipoprotein
      cholesterol, high-density lipoprotein cholesterol, and triglycerides levels
      compared with the chromium trichloride and chromium picolinate groups.
      CONCLUSIONS: The results showed that chromium malate exhibits greater benefits in
      treating type 2 diabetes, and the curative effect of chromium malate is superior
      to chromium trichloride and chromium picolinate.

PMID- 26221519
TI  - Association between insulin resistance and plasma amino acid profile in non
      diabetic Japanese subjects.
AB  - AIMS/INTRODUCTION: Elevation of the branched-chain amino acids (BCAAs), valine,
      leucine and isoleucine; and the aromatic amino acids, tyrosine and phenylalanine,
      has been observed in obesity-related insulin resistance. However, there have been
      few studies on Asians, who are generally less obese and less insulin-resistant
      than Caucasian or African-Americans. In the present study, we investigated the
      relationship between homeostasis model assessment of insulin resistance (HOMA-IR)
      and plasma amino acid concentration in non-diabetic Japanese participants.
      MATERIALS AND METHODS: A total of 94 healthy men and women were enrolled, and
      plasma amino acid concentration was measured by liquid chromatography/mass
      spectrometry after overnight fasting. The associations between HOMA-IR and 20
      amino acid concentrations, and anthropometric and clinical parameters of
      lifestyle-related diseases were evaluated. RESULTS: The mean age and body mass
      index were 40.1 +/- 9.6 years and 22.7 +/- 3.9, respectively. Significantly
      positive correlations were observed between HOMA-IR and valine, isoleucine,
      leucine, tyrosine, phenylalanine and total BCAA concentration. Compared with the
      HOMA-IR <= 1.6 group, the HOMA-IR > 1.6 group showed significantly exacerbated
      anthropometric and clinical parameters, and significantly elevated levels of
      valine, isoleucine, leucine, tyrosine, phenylalanine and BCAA. CONCLUSIONS: The
      present study shows that the insulin resistance-related change in amino acid
      profile is also observed in non-diabetic Japanese subjects. These amino acids
      include BCAAs (valine, isoleucine and leucine) and aromatic amino acids (tyrosine
      and phenylalanine), in agreement with previous studies carried out using
      different ethnic groups with different degrees of obesity and insulin resistance.

PMID- 26221520
TI  - Association between the level of circulating adiponectin and prediabetes: A meta
      analysis.
AB  - AIMS/INTRODUCTION: Adiponectin has been proposed to have an essential role in the
      regulation of insulin sensitivity and metabolism, but previous studies on levels
      of adiponectin in prediabetes remain inconsistent. The present study aimed to
      assess the differences of adiponectin levels between prediabetes patients and
      healthy controls by carrying out a meta-analysis. MATERIALS AND METHODS: We
      carried out a systematic literature search of PubMed, EMBASE, and other databases
      for case-control studies and cohort studies measuring adiponectin levels in serum
      or plasma from prediabetes patients and healthy controls. The pooled weighted
      mean difference (WMD) and 95% confidence interval (CI) were used to estimate the
      association between adiponectin levels and prediabetes. RESULTS: Three cohort
      studies and 15 case-control studies with a total of 41,841 participants were
      included in the meta-analysis. The results showed that circulating adiponectin
      levels in prediabetes patients were significantly lower than that of healthy
      controls (WMD -1.694 MUg/mL; 95% CI -2.151, -1.237; P < 0.001). Subgroup analysis
      showed more significant differences between prediabetes patients and healthy
      controls when the ratio of the homeostatic model assessment of insulin resistance
      was >2.12 (WMD -2.95 MUg/mL; 95% CI -4.103, -1.806; P < 0.001) and average age
      was >60 years (WMD -2.20 MUg/mL; 95% CI -3.207, -1.201; P < 0.001). Additionally,
      WMD in adiponectin showed a trend of direct correlation in subgroups of
      homeostatic model assessment of insulin resistance ratio, body mass index and
      age. CONCLUSIONS: The present meta-analysis supports adiponectin levels in
      prediabetes patients being lower than that of healthy controls,indicating that
      the level of circulating adiponectin decreases before the onset of diabetes.

PMID- 26221521
TI  - Association of birthweight with diabetes and insulin sensitivity or secretion in
      the Japanese general population.
AB  - AIMS/INTRODUCTION: Low birthweight (birthweight <2,500 g) has been considered to
      be a risk factor for diabetes in data from Western countries, and its percentage
      is increasing in Japan. The aim of the present study was to assess the
      association between birth weight and diabetes, as well as both insulin resistance
      and secretion. MATERIALS AND METHODS: The participants were 847 adults who
      underwent health check-ups. The participants were divided by birthweight into
      four groups (low birthweight and tertiles 1-3 above it). We assessed the effect
      of birthweight on diabetes using a logistic regression model. Multivariable liner
      regression analyses were carried out to examine whether birthweight is
      independently associated with homeostasis model assessment of insulin resistance
      and beta-cell function. RESULTS: The prevalence of diabetes tended to increase
      with decreasing birthweight. The adjusted odds ratio for diabetes with low
      birthweight was 3.52 (1.04-11.96) as compared with the reference category,
      tertile 2. Univariable linear regression analyses showed that homeostasis model
      assessment of insulin resistance was negatively associated with birthweight, and
      this association remained after adjusting for age, sex, current body mass index
      and family history of diabetes. There was no significant association between
      homeostasis model assessment of beta-cell function and birthweight. CONCLUSIONS:
      Low birthweight was inversely associated with diabetes and insulin resistance in
      the Japanese general population. Longitudinal data analyses are required to
      examine the causal relationship between bodyweight and diabetes or insulin
      resistance in adulthood.

PMID- 26221522
TI  - Stabilization of postprandial blood glucose fluctuations by addition of glucagon
      like polypeptide-analog administration to intensive insulin therapy.
AB  - AIMS/INTRODUCTION: The nature of the action of concomitant liraglutide to
      stabilize postprandial blood glucose level (PBG) in patients on intensive insulin
      therapy with unstable PBG remains unclear. The aim was to identify the nature of
      liraglutide's actions to stabilize PBGs. MATERIALS AND METHODS: The study
      participants consisted of 20 diabetes patients showing unstable PBGs after dinner
      despite undergoing intensive insulin therapy. The dose of bolus insulin was
      reduced by three units for each meal, and 0.9 mg/day of liraglutide was added and
      used in combination. We evaluated the participants' data after the first
      evaluation (immediately before using liraglutide in combination) and the second
      evaluation (16 weeks after starting concomitant therapy). PBGs after dinner were
      measured every day for a period of 28 days immediately before carrying out both
      evaluations. The mean value of the 28 sets of blood glucose data and their
      standard deviation (SD) values were established as PBGs after dinner, as well as
      the SD for each participant. The changes in the mean values of the 20
      participants, as well as their SD between before and after concomitant therapy,
      were evaluated. RESULTS: The mean value of PBGs (12.0 +/- 1.0 to 10.1 +/- 0.9
      mmol/L) and SD values (5.1 +/- 0.7-3.5 +/- 0.8) after dinner both declined. A
      multiple regression analysis showed that the combined use of liraglutide was a
      significant independent variable of the SD values of PBGs after dinner.
      CONCLUSION: The treatment of reducing the dose of insulin and using liraglutide
      in combination not only suppresses PBGs, but also stabilizes their blood glucose
      fluctuations.

PMID- 26221523
TI  - Efficacy and safety of luseogliflozin added to various oral antidiabetic drugs in
      Japanese patients with type 2 diabetes mellitus.
AB  - INTRODUCTION: Two studies were carried out to investigate the efficacy and safety
      of luseogliflozin added to existing oral antidiabetic drugs (OADs) in Japanese
      type 2 diabetic patients inadequately controlled with OAD monotherapy. MATERIALS
      AND METHODS: In the trial involving add-on to sulfonylureas (study 03-1),
      patients were randomly assigned to receive luseogliflozin 2.5 mg or a placebo for
      a 24-week double-blind period, followed by a 28-week open-label period. In the
      open-label trial involving add-on to other OADs; that is, biguanides, dipeptidyl
      peptidase-4 inhibitors, thiazolidinediones, glinides and alpha-glucosidase
      inhibitors (study 03-2), patients received luseogliflozin for 52 weeks. RESULTS:
      In study 03-1, luseogliflozin significantly decreased glycated hemoglobin at the
      end of the 24-week double-blind period compared with the placebo (-0.88%, P <
      0.001), and glycated hemoglobin reduction from baseline at week 52 was -0.63%. In
      study 03-2, luseogliflozin added to other OADs significantly decreased glycated
      hemoglobin from baseline at week 52 (-0.52 to -0.68%, P < 0.001 for all OADs).
      Bodyweight reduction was observed in all add-on therapies, even with agents
      associated with weight gain, such as sulfonylureas and thiazolidinediones. Most
      adverse events were mild in severity. When added to a sulfonylurea, incidences of
      hypoglycemia during the double-blind period were 8.7% and 4.2% for luseogliflozin
      and placebo, respectively, but no major hypoglycemic episodes occurred. The
      frequency and incidences of adverse events of special interest for sodium glucose
      cotransporter 2 inhibitors and adverse events associated with combined OADs were
      acceptable. CONCLUSIONS: Add-on therapies of luseogliflozin to existing OADs
      improved glycemic control, reduced bodyweight and were well tolerated in Japanese
      type 2 diabetic patients. These trials were registered with the Japan
      Pharmaceutical Information Center (add on to sulfonylurea: JapicCTI-111507; add
      on to other OADs: JapicCTI-111508).

PMID- 26221524
TI  - Effects of sulfonylurea as initial treatment on testosterone of middle-aged men
      with type 2 diabetes: A 16-week, pilot study.
AB  - AIMS/INTRODUCTION: To evaluate the effect of sulfonylurea (glimepiride)-based
      oral antidiabetic agents on testosterone levels in middle-aged men with type 2
      diabetes. MATERIALS AND METHODS: As a substudy, 15 participants from the phase IV
      clinical trial of glimepiride (GREAT study) of middle-aged men with type 2
      diabetes were included in the current study. After enrolment, the initial dose of
      oral glimepiride was 1 mg/day. The dose was titrated according to blood glucose
      levels and the participants were treated for 16 weeks. Meanwhile, another 15
      healthy age- and body mass index-matched male subjects were randomly selected as
      the healthy control group. RESULTS: Compared with the healthy control group, the
      middle-aged men with type 2 diabetes had significantly decreased total
      testosterone levels and a lower testosterone secretion index. Blood glucose and
      lipid profile levels were significantly improved after 16 weeks of treatment with
      no significant differences in bodyweight and waist circumference compared with
      baseline values. Recorded changes in luteinizing hormone, follicle-stimulating
      hormone and sex hormone-binding globulin levels were not statistically
      significant. However, total testosterone levels were significantly increased and
      testosterone secretion index values were significant higher than those of the
      baseline. CONCLUSIONS: It is highly possible that sulfonylurea as an initial
      treatment can recover the decreased total serum testosterone levels and
      testosterone secretion index values in middle-aged men with type 2 diabetes.

PMID- 26221525
TI  - Are late-night eating habits and sleep duration associated with glycemic control
      in adult type 1 diabetes patients treated with insulin pumps?
AB  - AIMS/INTRODUCTION: Little is known about the impact of sleep duration and late
      night snacking on glycemic control in patients with type 1 diabetes using insulin
      pumps. The aim of the present study was to examine whether late-night eating
      habits and short sleep duration are associated with glycemic control in
      continuous subcutaneous insulin infusion-treated type 1 diabetic patients.
      MATERIALS AND METHODS: We included 148 consecutive adult type 1 diabetic subjects
      using an insulin pump (100 women and 48 men). Participants completed a
      questionnaire regarding sleep duration (classified as short if <=6 h) and late
      night snacking. Other sources of information included medical records and data
      from blood glucose meters. Glycemic control was assessed by glycated hemoglobin
      (HbA1c) levels and mean self-monitoring of blood glucose (SMBG) readings.
      RESULTS: The mean age of patients was 26 years, mean type 1 diabetes duration was
      13.4 years and mean HbA1c level was 7.2%. In a univariate regression analysis,
      sleep duration was a predictor of both HbA1c (beta = 0.51, P = 0.01) and SMBG
      levels (beta = 11.4, P = 0.02). Additionally, an association was found between
      frequent late-night snacking and higher SMBG readings (often snacking beta =
      18.1, P = 0.05), but not with increased HbA1c levels. In the multivariate linear
      regression, independent predictors for HbA1c and SMBG were sleep duration and
      patient age. In a univariate logistic regression, sleep duration and frequency of
      late-night snacking were not predictors of whether HbA1c target levels were
      achieved. CONCLUSIONS: Short sleep duration, but not late-night snacking, seems
      to be associated with poorer glycemic control in type 1 diabetic patients treated
      with continuous subcutaneous insulin infusion.

PMID- 26221527
TI  - Decreased levels of circulating CD34(+) cells are associated with coronary heart
      disease in Japanese patients with type 2 diabetes.
AB  - AIMS/INTRODUCTION: Circulating progenitor cells, including CD34 positive
      (CD34(+)) cells, play a key role in neovascularisation and the maintenance of
      vascular endothelial function. Several lines of evidence show an association
      between decreased levels of circulating CD34(+) cells and cardiovascular disease.
      However, the contribution of circulating CD34(+) cells to the occurrence of
      cardiovascular events in diabetic patients remains unclear. MATERIALS AND
      METHODS: In the present study with a median follow up of 4.6 years, we analyzed
      the level of circulating CD34(+) cells in 192 patients with type 2 diabetes. The
      outcome variables were coronary heart disease (CHD) events (cardiovascular death,
      unstable angina, myocardial infarction, percutaneous coronary intervention or
      coronary artery bypass grafting) and cerebrovascular disease events (cerebral
      infarction, cerebral hemorrhage or transient ischemic attack). RESULTS: Decreased
      levels of circulating CD34(+) cells were associated with a significantly higher
      incidence of CHD based on Kaplan-Meier analysis (P = 0.0052). After adjusting for
      age, sex, dyslipidemia, hypertension, glycated hemoglobin, history of
      cardiovascular disease, body mass index, and statin and renin angiotensin system
      inhibitors use, decreased levels of CD34(+) cells were significantly associated
      with the incidence of CHD events (hazard ratio of low tertile 2.61, 95%
      confidence interval 1.22-5.96; P = 0.013, reference; high tertile). CONCLUSIONS:
      Decreased levels of circulating CD34(+) cells might predict CHD events in
      patients with diabetes, and this could be useful for identifying patients with
      diabetes at high risk of cardiovascular events.

PMID- 26221526
TI  - Lower vegetable protein intake and higher dietary acid load associated with lower
      carbohydrate intake are risk factors for metabolic syndrome in patients with type
      2 diabetes: Post-hoc analysis of a cross-sectional study.
AB  - AIMS/INTRODUCTION: A low-carbohydrate diet based on animal sources is associated
      with higher all-cause mortality, whereas a vegetable-based low-carbohydrate diet
      is associated with lower cardiovascular disease mortality. It has been suggested
      that acid/base imbalance might play an important role in some cardiometabolic
      abnormalities. The aims of the present study were to evaluate whether
      carbohydrate intake is associated with quality of dietary protein and acid load,
      and whether these are related to metabolic syndrome in patients with type 2
      diabetes. MATERIALS AND METHODS: The present cross-sectional study involved 149
      patients with type 2 diabetes. Dietary intake was assessed using a validated self
      administered diet history questionnaire. Dietary acid load was assessed by
      potential renal acid load and net endogenous acid production. RESULTS: Mean daily
      total energy intake, carbohydrate intake, animal protein intake and vegetable
      protein intake were 1821.5 kcal, 248.8 g, 36.1 g and 31.1 g, respectively.
      Carbohydrate energy/total energy was negatively correlated with animal protein
      energy/total energy, potential renal acid load or net endogenous acid production
      score, and was positively correlated with vegetable protein energy/total energy.
      Logistic regression analyses showed that the subgroup of patients with a lower
      vegetable protein energy/total energy or higher potential renal acid load or net
      endogenous acid production score was significantly associated with the prevalence
      of metabolic syndrome. CONCLUSIONS: The present study showed that carbohydrate
      intake was associated with the quality of dietary protein and dietary acid load.
      Furthermore, decreased vegetable protein intake and increased dietary acid load
      were associated with the prevalence of metabolic syndrome.

PMID- 26221528
TI  - Effect of peer education on self-management and psychological status in type 2
      diabetes patients with emotional disorders.
AB  - AIMS/INTRODUCTION: The purpose of the present study was to assess the effect of
      peer education in type 2 diabetes patients with emotional disorders on the
      metabolic index and psychological status. MATERIALS AND METHODS: Educators use
      psychological scales to screen type 2 diabetes patients with emotional disorders.
      Participants were divided into usual and peer education groups. Both groups
      received usual diabetes education. Peer leaders were recruited to provide support
      with the peer education group for 6 months. The metabolic index, diabetes
      knowledge, self-management, diabetes-related distress, emotional status and
      quality of life were compared at the end of the study. RESULTS: A total of 127
      patients participated in the study. There were 20 peer leaders engaged in the
      study as volunteers for peer education. All participants completed the study and
      fulfilled the scales. Improvements in the peer education group were significant
      compared with the usual education group with respect to anxiety (49.0 +/- 9.65 vs
      54.0 +/- 8.48), depression (51.3 +/- 7.97 vs 55.8 +/- 7.52), diabetes knowledge
      (18.8 +/- 2.46 vs 16.3 +/- 2.08), distress (2.67 +/- 0.55 vs 3.02 +/- 0.56), self
      management (66.5 +/- 4.26 vs 62.4 +/- 5.88) and quality of life (-1.98 +/- 0.82
      vs -2.50 +/- 0.71), whereas no significant difference existed with respect to the
      metabolic index. CONCLUSIONS: Peer education, providing more attention to
      diabetes patients with emotional disorders, is a preferred model for delivering
      care.

PMID- 26221530
TI  - Erratum.

PMID- 26221529
TI  - Pseudoaldosteronism induced by Yokukansan in an elderly Japanese type 2 diabetic
      patient with Alzheimer's disease.

PMID- 26221532
TI  - Hypoxic metabolism in human hematopoietic stem cells.
AB  - BACKGROUND: Adult hematopoietic stem cells (HSCs) are maintained in a
      microenvironment, known as niche in the endosteal regions of the bone marrow.
      This stem cell niche with low oxygen tension requires HSCs to adopt a unique
      metabolic profile. We have recently demonstrated that mouse long-term
      hematopoietic stem cells (LT-HSCs) utilize glycolysis instead of mitochondrial
      oxidative phosphorylation as their main energy source. However, the metabolic
      phenotype of human hematopoietic progenitor and stem cells (HPSCs) remains
      unknown. RESULTS: We show that HPSCs have a similar metabolic phenotype, as shown
      by high rates of glycolysis, and low rates of oxygen consumption. Fractionation
      of human mobilized peripheral blood cells based on their metabolic footprint
      shows that cells with a low mitochondrial potential are highly enriched for
      HPSCs. Remarkably, low MP cells had much better repopulation ability as compared
      to high MP cells. Moreover, similar to their murine counterparts, we show that
      Hif-1alpha is upregulated in human HPSCs, where it is transcriptionally regulated
      by Meis1. Finally, we show that Meis1 and its cofactors Pbx1 and HoxA9 play an
      important role in transcriptional activation of Hif-1alpha in a cooperative
      manner. CONCLUSIONS: These findings highlight the unique metabolic properties of
      human HPSCs and the transcriptional network that regulates their metabolic
      phenotype.

PMID- 26221533
TI  - PTEN signaling is required for the maintenance of spermatogonial stem cells in
      mouse, by regulating the expressions of PLZF and UTF1.
AB  - BACKGROUND: Pten plays a crucial role in the stem cell maintenance in a few
      organs. Pten defect also causes the premature oocytes and ovary aging. We and
      other groups have found that the phosphatidylinositol-3-OH kinase (PI3K)-Akt
      signaling regulates the proliferation and differentiation of spermatogonial stem
      cells (SSCs). PTEN functions as a negative regulator of the PI3K pathway. Thus,
      we thought that the fate of SSCs might be controlled by Pten. RESULTS: We report
      that promyelocytic leukaemia zinc finger (PLZF) and undifferentiated embryonic
      cell transcription factor 1 (UTF1), both of which are germ cell-specific
      transcriptional factors, are regulated by Pten. Conditional deletion of Pten
      leads to reduction in PLZF expression but induction of UTF1, which is associated
      with SSCs depletion and infertility in males with age. CONCLUSION: Our data
      demonstrate that Pten is required for the long-term maintenance of SSCs and
      precise regulation of spermatogenesis in mouse. The finding of a Pten-regulated
      GFRalpha1(+)/PLZF(-)/UTF1(+) progenitor population provides a new insight into
      the precise mechanisms controlling SSC fate.

PMID- 26221534
TI  - Socio-cultural features and help-seeking preferences for leprosy and
      turbeculosis: a cultural epidemiological study in a tribal district of
      Maharashtra, India.
AB  - BACKGROUND: India is a major contributor to the global burden of leprosy and
      tuberculosis (TB), which adversely affects the poorest tribal communities.
      Despite prioritisation by disease control programmes, programme performance for
      leprosy and TB in tribal communities continues to be a challenge. In addition to
      access to services and infrastructural limitations, socio-cultural concepts of
      illness causation and related help seeking (HS) rooted in distinct features of
      tribal culture need to be addressed to improve programme outcomes. METHODS: A
      cultural epidemiological survey of leprosy and TB patients was carried out using
      a locally adapted, semi-structured explanatory model interviews. A total of 100
      leprosy and 50 TB patients registered for treatment at government health
      facilities were selected randomly from tribal dominant blocks of the Thane
      district, Maharashtra state. The perceived causes (PCs) of leprosy and TB in
      patients were compared based on prominence categories. The relationship between
      PCs as predictors, and disease conditions and HS preferences as outcome variables
      were assessed using multivariate logistic regression. RESULTS: In the
      multivariate logistic regression model with disease conditions as outcome
      variables, TB patients were significantly more likely to report PCs in the
      categories of ingestion; health, illness and injury; and traditional, cultural
      and supernatural. Tuberculosis patients more frequently first sought help from
      private facilities as compared to leprosy patients who preferred government
      health facilities. In a combined analysis of leprosy and TB patients employing
      multivariate logistic regression, it was found that patients who reported PCs in
      the environmental and contact-related categories were more likely to visit
      traditional rather than non-traditional practitioners. In another multivariate
      combined model, it was found that patients who reported PCs in the traditional,
      cultural and supernatural category were significantly more likely to visit
      private rather than public health facilities. CONCLUSION: Cultural concepts about
      illness causation and associated HS behaviours should be considered as priorities
      for action, which in turn would provide the necessary impetus to ensure that
      tribal patients seek help in a timely and appropriate manner, and could
      facilitate improvement in programme performance in general.

PMID- 26221535
TI  - Hierarchical distance-based fuzzy approach to evaluate urban water supply systems
      in a semi-arid region.
AB  - Hierarchical distance-based fuzzy multi-criteria group decision making was served
      as a tool to evaluate the drinking water supply systems of Qom, a semi-arid city
      located in central part of Iran. A list of aspects consisting of 6 criteria and
      35 sub-criteria were evaluated based on a linguistic term set by five decision
      makers. Four water supply alternatives including "Public desalinated distribution
      system", "PET Bottled Drinking Water", "Private desalinated water suppliers" and
      "Household desalinated water units" were assessed based on criteria and sub
      criteria. Data were aggregated and normalized to apply Performance Ratings of
      Alternatives. Also, the Performance Ratings of Alternatives were aggregated again
      to achieve the Aggregate Performance Ratings. The weighted distances from ideal
      solution and anti-ideal solution were calculated after secondary normalization.
      The proximity of each alternative to the ideal solution was determined as the
      final step. The alternatives were ranked based on the magnitude of ideal
      solutions. Results showed that "Public desalinated distribution system" was the
      most appropriate alternative to supply the drinking needs of Qom population.
      Also, "PET Bottled Drinking Water" was the second acceptable option. A novel
      classification of alternatives to satisfy the drinking water requirements was
      proposed which is applicable for the other cities located in semi-arid regions of
      Iran. The health issues were considered as independent criterion, distinct from
      the environmental issues. The constraints of high-tech alternatives were also
      considered regarding to the level of dependency on overseas. 

PMID- 26221536
TI  - Surveillance of perchlorate in ground water, surface water and bottled water in
      Kerala, India.
AB  - BACKGROUND: Perchlorate is an emerging water contaminant that disrupts normal
      functioning of human thyroid gland and poses serious threat to health, especially
      for pregnant women, fetus and children. RESULTS: High level of perchlorate
      contamination in fresh water sources at places nearby ammonium perchlorate
      (rocket fuel) handled in bulk is reported in this study. Of 160 ground water
      samples analyzed from 27 locations in the State Kerala, 58 % had perchlorate
      above detection limit (2 MUg/L) and the highest concentration observed was 7270
      MUg/L at Ernakulam district, this value is ~480 times higher than USEPA drinking
      water equivalent level (15 MUg/L). Perchlorate was detected in all surface water
      samples analyzed (n = 10) and the highest value observed was 355 MUg/L in Periyar
      river (a major river in the State). The bottled drinking water (n = 5) tested
      were free of perchlorate. CONCLUSIONS: The present study underlines the need for
      frequent screening of water sources for perchlorate contamination around places
      the chemical is handled in bulk. It will help to avoid human exposure to high
      levels of perchlorate.

PMID- 26221537
TI  - Anti-Biofilm and Immunomodulatory Activities of Peptides That Inhibit Biofilms
      Formed by Pathogens Isolated from Cystic Fibrosis Patients.
AB  - Cystic fibrosis (CF) patients often acquire chronic respiratory tract infections
      due to Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc) species. In
      the CF lung, these bacteria grow as multicellular aggregates termed biofilms.
      Biofilms demonstrate increased (adaptive) resistance to conventional antibiotics,
      and there are currently no available biofilm-specific therapies. Using plastic
      adherent, hydroxyapatite and flow cell biofilm models coupled with confocal and
      scanning electron microscopy, it was demonstrated that an anti-biofilm peptide
      1018 prevented biofilm formation, eradicated mature biofilms and killed biofilms
      formed by a wide range of P. aeruginosa and B. cenocepacia clinical isolates. New
      peptide derivatives were designed that, compared to their parent peptide 1018,
      showed similar or decreased anti-biofilm activity against P. aeruginosa biofilms,
      but increased activity against biofilms formed by the Gram-positive bacterium
      methicillin resistant Staphylococcus aureus. In addition, some of these new
      peptide derivatives retained the immunomodulatory activity of 1018 since they
      induced the production of the chemokine monocyte chemotactic protein-1 (MCP-1)
      and suppressed lipopolysaccharide-mediated tumor necrosis factor-alpha (TNF
      alpha) production by human peripheral blood mononuclear cells (PBMC) and were non
      toxic towards these cells. Peptide 1018 and its derivatives provide promising
      leads for the treatment of chronic biofilm infections and hyperinflammatory lung
      disease in CF patients. 

PMID- 26221538
TI  - Clinical Outcomes of Small Incision Lenticule Extraction with Accelerated Cross
      Linking (ReLEx SMILE Xtra) in Patients with Thin Corneas and Borderline
      Topography.
AB  - Purpose. To study the safety and clinical outcomes of ReLEx SMILE with
      accelerated cross-linking in individuals with thinner corneas, borderline
      topography, and higher refractive errors. Methods. Eligible patients first
      underwent SMILE procedure for correction of myopic refractive error. Following
      the removal of lenticule, 0.25% riboflavin in saline was injected into the
      interface and allowed to diffuse for 60 seconds. Finally, eye was exposed to UV-A
      radiation of 45 mW/cm(2) for 75 seconds through the cap. Total energy delivered
      was 3.4 J/cm(2). Results. 40 eyes of 20 patients with mean age of 26.75 +/- 5.99
      years were treated. Mean follow-up was 12 months +/- 28.12 days. Mean spherical
      equivalent (SE) was -5.02 +/- 2.06 D preoperatively and -0.24 +/- 0.18 D
      postoperatively. The mean central corneal thickness (CCT) and keratometry changed
      from 501 +/- 25.90 um to 415 +/- 42.26 um and 45.40 +/- 1.40 D to 41.2 +/- 2.75
      D, respectively. Mean uncorrected visual acuity (UCVA) was 20/25 or better in all
      eyes. No eyes lost lines of corrected distant visual acuity (CDVA). There were no
      complications like haze, keratitis, ectasia, or regression. Conclusion. Based on
      the initial clinical outcome it appears that SMILE Xtra may be a safe and
      feasible modality to prevent corneal ectasia in susceptible individuals. 

PMID- 26221540
TI  - Corrigendum to "Transvaginal Appendectomy: A Systematic Review".
AB  - [This corrects the article DOI: 10.1155/2014/384706.]. 

PMID- 26221539
TI  - Efficacy and Acceptability of Orthokeratology for Slowing Myopic Progression in
      Children: A Systematic Review and Meta-Analysis.
AB  - Background. To evaluate the efficacy and acceptability of orthokeratology for
      slowing myopic progression in children with a well conducted evidence-based
      analysis. Design. Meta-analysis. Participants. Children from previously reported
      comparative studies were treated by orthokeratology versus control. Methods. A
      systematic literature retrieval was conducted in MEDLINE, EMBASE, Cochrane
      Library, World Health Organization International Clinical Trials Registry
      Platform, and ClinicalTrials.gov. The included studies were subjected to meta
      analysis using Stata version 10.1. Main Outcome Measures. Axial length change
      (efficacy) and dropout rates (acceptability) during 2-year follow-up. Results.
      Eight studies involving 769 subjects were included. At 2-year follow-up, a
      statistically significant difference was observed in axial length change between
      the orthokeratology and control groups, with a weighted mean difference (WMD) of 
      0.25 mm (95% CI, -0.30 to -0.21). The pooled myopic control rate declined with
      time, with 55, 51, 51, and 41% obtained after 6, 12, 18, and 24 months of
      treatment, respectively. No statistically significant difference was obtained for
      dropout rates between the orthokeratology and control groups at 2-year follow-up
      (OR, 0.79; 95% CI, 0.52 to 1.22). Conclusions. Orthokeratology is effective and
      acceptable for slowing myopic progression in children with careful education and
      monitoring. 

PMID- 26221541
TI  - Antiepileptic and Antidepressive Polypharmacy in Patients with Multiple
      Sclerosis.
AB  - Objective. Patients with multiple sclerosis (MS) are often suffering from
      neuropathic pain. Antiepileptic drugs (AEDs) and tricyclic antidepressants (TCAs)
      are commonly used and are susceptible to be involved in drug interactions. The
      aim of this retrospective study was to investigate the prevalence of use of
      antiepileptic and antidepressive drugs in MS patients and to discuss the
      theoretical potential for interactions. Methods. Review of the medical records
      from all patients treated at a dedicated MS rehabilitation centre in Norway
      between 2009 and 2012. Results. In total 1090 patients attended a rehabilitation
      stay during the study period. Of these, 342 (31%; 249 females) with mean age of
      53 (+/-10) years and EDSS 4.8 (+/-1.7) used at least one AED (gabapentin 12.7%,
      pregabalin 7.7%, clonazepam 7.8%, and carbamazepine 2.6%) or amitriptyline
      (9.7%). Polypharmacy was widespread (mean 5.4 drugs) with 60% using additional
      CNS-active drugs with a propensity to be involved in interactions. Age, gender,
      and EDSS scores did not differ significantly between those using and not using
      AED/amitriptyline. Conclusion. One-third of MS patients attending a
      rehabilitation stay receive AED/amitriptyline treatment. The high prevalence of
      polypharmacy and use of CNS-active drugs calls for awareness of especially
      pharmacodynamic interactions and possible excessive adverse effects. 

PMID- 26221542
TI  - Evaluation of Sentinel Lymph Node Dose Distribution in 3D Conformal Radiotherapy
      Techniques in 67 pN0 Breast Cancer Patients.
AB  - Introduction. The anatomic position of the sentinel lymph node is variable. The
      purpose of the following study was to assess the dose distribution delivered to
      the surgically marked sentinel lymph node site by 3D conformal radio therapy
      technique. Material and Method. We retrospectively analysed 70 radiotherapy (RT)
      treatment plans of consecutive primary breast cancer patients with a successful,
      disease-free, sentinel lymph node resection. Results. In our case series the SN
      clip volume received a mean dose of 40.7 Gy (min 28.8 Gy/max 47.6 Gy).
      Conclusion. By using surgical clip markers in combination with 3D CT images our
      data supports the pathway of tumouricidal doses in the SN bed. The target volume
      should be defined by surgical clip markers and 3D CT images to give accurate dose
      estimations. 

PMID- 26221544
TI  - Normalization of Activated Partial Thromboplastin Time Correlates with Low Levels
      of Dabigatran in a Patient with Severe Sepsis.
AB  - The oral anticoagulant dabigatran etexilate can be a challenge when patients need
      acute surgery. Sepsis and acute renal failure exacerbate the anticoagulant
      effect. There is no specific reversal agent for dabigatran etexilate, but it can
      be removed by hemodialysis. We present a case where a patient treated with
      dabigatran etexilate was admitted to intensive care unit with severe sepsis and
      acute renal failure and in need of bilateral lower limp amputation due to
      ischemia. The patient had severe coagulopathy and was treated with continuous
      venovenous hemofiltration in attempt to remove dabigatran etexilate before
      surgery. 

PMID- 26221545
TI  - Neurilemmoma of Retromolar Region in the Oral Cavity.
AB  - Neurilemmoma also known as schwannoma is benign nerve sheath tumor rarely
      occurring in the oral cavity. Only 1% of all extracranial schwannomas show that
      intraoral occurrence with tongue is the commonest site and retromolar region is
      the least common site. It presents as encapsulated, slow growing, solitary,
      smooth-surfaced, usually asymptomatic tumor. We report a case of 70-year-old male
      with well-defined mass on left retromolar region which was painless and slow
      growing. Diagnosis is made by histological examination and immunohistochemistry
      analysis to confirm the neural tissue origin of the lesion. The treatment is
      complete surgical excision of the lesion without recurrence. 

PMID- 26221543
TI  - A Neurologist's Guide to TNF Biology and to the Principles behind the Therapeutic
      Removal of Excess TNF in Disease.
AB  - Tumor necrosis factor (TNF) is an ancient and widespread cytokine required in
      small amounts for much physiological function. Higher concentrations are central
      to innate immunity, but if unchecked this cytokine orchestrates much chronic and
      acute disease, both infectious and noninfectious. While being a major
      proinflammatory cytokine, it also controls homeostasis and plasticity in
      physiological circumstances. For the last decade or so these principles have been
      shown to apply to the central nervous system as well as the rest of the body.
      Nevertheless, whereas this approach has been a major success in treating
      noncerebral disease, its investigation and potential widespread adoption in
      chronic neurological conditions has inexplicably stalled since the first open
      trial almost a decade ago. While neuroscience is closely involved with this
      approach, clinical neurology appears to be reticent in engaging with what it
      offers patients. Unfortunately, the basic biology of TNF and its relevance to
      disease is largely outside the traditions of neurology. The purpose of this
      review is to facilitate lowering communication barriers between the traditional
      anatomically based medical specialties through recognition of shared disease
      mechanisms and thus advance the prospects of a large group of patients with
      neurodegenerative conditions for whom at present little can be done. 

PMID- 26221546
TI  - Lymphatic Malformation, Retinoblastoma, or Facial Cleft: Atypical Presentations
      of PHACE Syndrome.
AB  - PHACE syndrome is a neurocutaneous disorder characterized by large cervicofacial
      infantile hemangiomas and associated anomalies: posterior fossa brain
      malformation, hemangioma, arterial cerebrovascular anomalies, coarctation of the
      aorta and cardiac defects, and eye/endocrine abnormalities of the brain. When
      ventral developmental defects (sternal clefting or supraumbilical raphe) are
      present the condition is termed PHACE. In this report, we describe three PHACE
      cases that presented unique features (affecting one of the organ systems
      described for this syndrome) that have not been described previously. In the
      first case, a definitive PHACE association, the patient presented with an
      ipsilateral mesenteric lymphatic malformation, at the age of 14 years. In the
      second case, an anomaly of the posterior segment of the eye, not mentioned before
      in PHACE literature, a retinoblastoma, has been described. Specific chemotherapy
      avoided enucleation. And, in the third case, the child presented with an unusual
      midline frontal bone cleft, corresponding to Tessier 14 cleft. Two patients'
      hemangiomas responded well to propranolol therapy. The first one was followed and
      treated in the pre-propranolol era and had a moderate response to corticoids and
      interferon. 

PMID- 26221547
TI  - Temozolomide-Induced Shrinkage of Invasive Pituitary Adenoma in Patient with
      Nelson's Syndrome: A Case Report and Review of the Literature.
AB  - Introduction. Invasive tumours in Nelson's syndrome need aggressive therapy.
      Recent reports have documented the efficacy of temozolomide (TMZ) in the
      treatment of adenomas resistant to conventional management. Objective. The review
      of the literature concerning TMZ treatment of atypical corticotroph adenomas and
      a case study of 56-year-old woman who developed Nelson's syndrome. Treatment
      Proceeding. The patient with Cushing's disease underwent transsphenoidal
      adenomectomy followed by a 27-month-long period of remission. Due to a regrowth
      of the tumor, she underwent two reoperations followed by stereotactic
      radiotherapy. Because of treatment failures, bilateral adrenalectomy was
      performed. Then she developed Nelson's syndrome. A fourth transsphenoidal
      adenomectomy was performed, but there was a rapid recurrence. Five months later,
      she underwent a right frontotemporal craniotomy. Due to a rapid regrowth of the
      tumour, the patient did not receive gamma-knife therapy and was treated with
      cabergoline and somatostatin analogue for some time. Only TMZ therapy resulted in
      marked clinical, biochemical, and radiological improvement. To date, this is the
      first case of invasive corticotroph adenoma in Nelson's syndrome treated with
      temozolomide in Poland. Conclusion. In our opinion, temozolomide can be an
      effective treatment option of invasive adenomas in Nelson's syndrome. 

PMID- 26221548
TI  - Sickle Cell Trait Causing Splanchnic Venous Thrombosis.
AB  - Sickle cell trait is considered as a benign condition as these individuals carry
      only one defective gene and typically have their life span similar to the normal
      population without any health problems related to sickle cell. Only under extreme
      conditions, red cells become sickled and can cause clinical complications
      including hematuria and splenic infarction. Although twofold increased risk of
      venous thrombosis has been described in African Americans, there is no data
      available from Indian population. We here report a case of sickle cell trait from
      India whose index presentation was thrombosis of unusual vascular territory. 

PMID- 26221549
TI  - Postpartum Ovarian Vein Thrombophlebitis with Staphylococcal Bacteremia.
AB  - A 34-year-old female patient presented with fever and right flank pain ten days
      after uncomplicated vaginal delivery. CT examination revealed right ovarian vein
      thrombosis and methicillin-resistant Staphylococcus aureus (MRSA) was isolated
      from blood cultures. No other source of bacteremia was found. Antibiotic therapy
      and anticoagulation with enoxaparin were instituted. Fourteen days after
      admission, she was discharged in good condition. Although a very uncommon
      complication after spontaneous vaginal delivery, septic ovarian vein
      thrombophlebitis should be suspected in cases of persistent puerperal fever when
      other diagnostic possibilities have been excluded. 

PMID- 26221550
TI  - Gestational Weight Gain and Peripartum Cardiomyopathy in a Twin Pregnancy.
AB  - Preeclamptic twin pregnancy with larger gestational weight gain (GWG) is
      suggested to have a higher risk of peripartum cardiomyopathy (PPCM). This was
      true in a 5-year experience at a single center. A primiparous woman with twins
      and prepregnancy weight of 51.0 kg exhibited hypertension at gestational week
      (GW) 32(-6/7) and GWG of 18.3 kg (6.0 kg and 2.9 kg during the last four weeks
      and one week of gestation, resp.) concomitant with generalized edema, gave birth
      at GW 34(-4/7), developed proteinuria, cough, and dyspnea postpartum, and was
      diagnosed with preeclampsia and PPCM showing left ventricular ejection fraction
      of 34% and plasma BNP level of 1530 pg/mL. This was the only case of PPCM among
      101 (12 with preeclampsia) and 3266 women with twin and singleton pregnancies,
      respectively. Thus, PPCM occurred significantly more often in women with
      preeclamptic twin pregnancies than in women with singleton pregnancies (8.3%
      [1/12] versus 0.0% [0/3266], P = 0.0355). This patient showed the greatest weight
      gain of 6.0 kg during the last four weeks of gestation and the greatest weight
      loss of 19.2 kg during one month postpartum among 90 women with twin deliveries
      at GW >= 32. 

PMID- 26221551
TI  - Endometrial Stromal Nodule: A Rarity and a Pathological Challenge.
AB  - Endometrial stromal tumors are rare, and endometrial stromal nodule is the least
      common. In the region of Middle Jutland, Denmark, only two cases are reported
      since 1995. The nodules are benign; nevertheless, hysterectomy is the treatment
      of choice. Tumor margins are required for diagnosis and essential to
      differentiate it from an invasive stromal sarcoma whose prognosis is very
      different. We report a rare case of a 38-year-old woman, with presurgical
      diagnosis of a uterine tumor/polyp. She presented with nausea and changes in
      bleeding pattern and initially had a transcervical polyp resection performed.
      Histopathological examination showed the presence of an endometrial stromal tumor
      with unclear margins, and an invasive malignant endometrial sarcoma could not be
      excluded. Pathological examination revealed an endometrial stromal nodule with
      invasion, not exceeding three mm. Endometrial stromal tumors are interesting due
      to their rare existence and difficulties in establishing a histological
      diagnosis. Although endometrial stromal nodules are benign entities, they must be
      differentiated from the other invasive malignant stromal tumors, which may change
      the final prognosis. No preoperative diagnostic tools are at hand, and benign as
      well as malignant tumors are treated with hysterectomy. 

PMID- 26221552
TI  - Brittle Cornea Syndrome: Case Report with Novel Mutation in the PRDM5 Gene and
      Review of the Literature.
AB  - A 3-year-old boy presented with acute corneal hydrops on the left eye and
      spontaneous corneal rupture on the right eye. A diagnosis of brittle cornea
      syndrome was confirmed by molecular analysis. A novel mutation, the homozygous
      variant c.17T>G, p.V6G, was found in the gene for PR-domain-containing protein 5
      (PRDM5) in exon 1. Brittle cornea syndrome is a rare connective tissue disease
      with typical ocular, auditory, musculoskeletal, and cutaneous disorders. Almost
      all patients suffer from declined vision due to corneal scarring, thinning, and
      rupture. The most common ophthalmologic findings include keratoconus, progressive
      central corneal thinning, high myopia, irregular astigmatism, retinal detachment,
      and high risk for spontaneous corneal or scleral rupture. In addition to
      describing the case with a novel mutation here we review the current literature
      on brittle cornea syndrome pathogenesis, clinical findings, and therapy. 

PMID- 26221553
TI  - Phenotypic Spectrum of Granular Corneal Dystrophy Type II in Two Italian Families
      Presenting an Unusual Granular Corneal Dystrophy Type I Clinical Appearance.
AB  - Clinical, instrumental, and genetic findings are reported in Italian families
      with Type II Granular Corneal Dystrophies (GCD2) presenting an initial unusual
      presentation of a Granular Corneal Dystrophy Type I (GCD1) phenotypic spectrum in
      female descendants. Slit-lamp examinations showed the typical phenotypic features
      of GCD2 in both mothers and a phenotypic appearance of GCD1 in both daughters.
      Despite the different phenotypic onset, the genetic diagnostic testing revealed
      the presence of a mutation in the TGFB-I gene, typical of GCD2 in both cases,
      excluding GCD1. Patients who were clinically suspected of corneal dystrophy need
      a genetic confirmatory testing for certain diagnosis. Genetic test may help to
      find the specific mutation distinguishing between different phenotypic spectra
      with relative diagnostic and prognostic implications. The study demonstrates that
      the phenotypic spectrum of genetically confirmed granular corneal dystrophies in
      patients may change over time. Since the R124H mutation has also been described
      in clinically asymptomatic individuals prior to LASIK, who then develop dramatic
      deposition, suggesting that this particular mutation and phenotype may be
      sensitive to, precipitated, or modified by central cornea trauma, a careful
      familial anamnesis excluding cornel dystrophies and specific preoperative genetic
      test are recommended prior to LASIK. 

PMID- 26221554
TI  - Posterior Chamber Hemorrhage during Fluorescein Angiography.
AB  - This paper provides the first reported case of acute posterior chamber hemorrhage
      during fluorescein angiography (FA). This is a case review with serial color
      photographs of the anterior segment. A 76-year-old male was referred for
      angiographic control of age-related macular degeneration. He was pseudophakic OU,
      BCVA 20/40 OU. He had mild hypertension, but not diabetes. He had had two
      previous angiograms without adverse effects. Difficulty was experienced in
      obtaining the images owing to a progressive reduction in the transparency of the
      media. A dense hemorrhage in the posterior chamber of the right eye was found,
      involving the visual axis. Thorough biomicroscopy, gonioscopy, and ultrasonic
      biomicroscopy showed that part of one of the haptics of the right intraocular
      lens (IOL) was touching and tearing the posterior face of the iris, without any
      visible synechiae, iris, or angle neovascularization. Anterior segment FA and
      posterior ultrasonography were normal. No similar case has been described in the
      literature involving dense progressive bleeding located in the capsular bag and
      posterior chamber, without any detectable triggering ocular event other than
      mydriasis and fluorescein injection. Contact of the iris or sulcus with part of
      the intraocular lens, aggravated by the intense use of mydriatics during the FA
      procedure, probably caused bleeding to happen. 

PMID- 26221555
TI  - Anterior Cruciate Ligament Reconstruction in Ehlers-Danlos Syndrome.
AB  - This report details the reconstruction of the anterior cruciate ligament in an 18
      year-old man with Ehlers-Danlos syndrome (EDS). The reduced mechanical properties
      of the tissue in EDS can pose a challenge to the orthopaedic surgeon. In this
      case, we describe the use of a hamstring autograft combined with a Ligament
      Advanced Reinforcement System (LARS). There was a good radiographical, clinical,
      and functional outcome after two years. This technique gave a successful outcome
      in the reconstruction of the ACL in a patient with EDS and therefore may help
      surgeons faced with the same clinical scenario. 

PMID- 26221556
TI  - Pulmonary Artery Cement Embolism after a Vertebroplasty.
AB  - Background Context. Vertebroplasty is a minimally invasive procedure most
      commonly used for the treatment of vertebral compression fractures. Although it
      is relatively safe, complications have been reported over time. Among those
      complications, massive cement pulmonary embolism is considered a rare
      complication. Here we report a case of massive diffuse cement pulmonary embolism
      following percutaneous vertebroplasty for a vertebral compression fracture. Study
      Design. CASE REPORT: Methods. This is a 70-year-old female who underwent
      vertebroplasty for T11 and T12 vertebral compression fracture. Results. CT-scan
      revealed an incidental finding of cement embolism in the pulmonary trunk and both
      pulmonary arteries. Since the patient was asymptomatic, she was monitored closely
      and she did not need any intervention. Conclusion. Vertebroplasty is a minimally
      invasive procedure used for treatment of vertebral compression fracture. Despite
      the low rate of complications, a pulmonary cement embolism can occur. The
      consequences of cement embolism range widely from being asymptomatic to embolism
      that can cause paralysis, radiculopathy, or a fatal pulmonary embolism.

PMID- 26221557
TI  - Pediatric Masked Mastoiditis Associated with Multiple Intracranial Complications.
AB  - Masked mastoiditis is a distinct form of mastoiditis with little or no
      symptomatology, characterized by its potential to generate severe otogenic
      complications. Therefore, suspected masked mastoiditis should be diagnosed and
      treated without delay. This study reports a rare case of masked mastoiditis,
      manifested by multiple intracranial complications in an immunocompetent girl. The
      child exhibited headache and neurological symptomatology. Imaging studies
      revealed an epidural and a large cerebellar abscess and the patient was
      immediately treated with a triple antibiotic therapy. Mastoid surgery and
      drainage of the epidural abscess took place after the stabilization of the
      patient's neurologic status, on the 3rd hospitalization day. The cerebellar
      abscess was treated by craniectomy and ultrasound-guided needle aspiration in the
      3rd week of hospitalization. The girl was finally discharged in excellent
      condition. Two years later, she is still in good health, without otological or
      neurological sequelae. Masked mastoiditis is an insidious disease which requires
      increased clinical awareness and adequate imaging. Should clinical and/or
      radiological findings be positive, mastoidectomy must follow in order to prevent
      severe otogenic complications that can be triggered by masked mastoiditis. 

PMID- 26221558
TI  - Primary Squamous Cell Carcinoma of Thyroid: A Rare Entity.
AB  - Primary squamous cell carcinoma (PSCC) of thyroid is an extremely rare malignancy
      of thyroid. Herewith, we describe a case report of female patient who presented
      with neck swelling; FNAC misdiagnosed it as papillary carcinoma of thyroid but,
      after resection, biopsy revealed it to be a case of squamous cell carcinoma of
      thyroid. After extensive investigations no possible primary focus of squamous
      cell carcinoma was found elsewhere, so diagnosis of primary squamous cell
      carcinoma of thyroid was made. Patient underwent chemoradiation but still patient
      succumbed to death within a year. 

PMID- 26221559
TI  - Cardiac Arrest following a Myocardial Infarction in a Child Treated with
      Methylphenidate.
AB  - The use of psychostimulants labeled to treat attention deficit/hyperactivity
      disorder increases. Among side effects these drugs raise blood pressure and heart
      rate, and the safety has been scrutinised in recent years. Data from large
      epidemiological studies, including over a million person-years, did not report
      any cases of myocardial infarction in current users of methylphenidate, and the
      risk of serious adverse cardiac events was not found to be increased. We present
      a case with an 11-year-old child, treated with methylphenidate, who suffered
      cardiac arrest and was diagnosed with a remote myocardial infarction. This
      demonstrates that myocardial infarction can happen due to methylphenidate
      exposure in a cardiac healthy child, without cardiovascular risk factors. 

PMID- 26221560
TI  - Transcolonic Migration of Retained Epicardial Pacing Wires.
AB  - Temporary epicardial pacing wires are associated with rare complications. Most of
      these occur in the chest. Even rarer are complications that occur within the
      abdomen. We report a case of migrating epicardial pacing wires entering the
      abdomen and penetrating the transverse colon found incidentally on colonoscopy in
      an asymptomatic patient. 

PMID- 26221561
TI  - Jejunal Intussusception: A Rare Presentation of Carcinoid Tumor.
AB  - A 55-year-old male presented to the emergency department with sudden onset of
      diffuse abdominal pain for one day. Physical examination was remarkable for
      tenderness in the umbilical region. A CT scan of the abdomen showed
      intussusception involving the jejunum without any mass. The patient then
      underwent an exploratory laparotomy. During surgery, the distal jejunum was
      intussuscepted with mesenteric lymphadenopathy. Liver showed nodular deposits in
      both lobes of the liver. The involved small bowel segment was resected with
      primary anastomosis and liver was biopsied. Pathological examination showed
      multifocal deposits of well-differentiated carcinoids in the jejunum. The liver
      and mesenteric deposits were positive for metastatic carcinoid. Patient recovered
      well without any complications. 

PMID- 26221562
TI  - Delayed Recognition of an Ureteropelvic Junction Obstruction in a Young Adult
      Female.
AB  - A percentage of ureteropelvic junction obstruction cases are clinically silent in
      childhood and manifest symptoms in adults. Herein we present a 25-year-old female
      with several years of intermittent flank pain and abdominal symptoms with prior
      inconclusive diagnostic workup including abdominal imaging without
      hydronephrosis. Ultimately, a CT scan performed during an acute pain crisis
      clearly identified right-sided hydronephrosis. The keys to diagnosis are
      awareness of this entity, a detailed history, and obtaining imaging studies
      during a crisis. The patient subsequently underwent a right robotic-assisted
      laparoscopic pyeloplasty with preservation of a lower pole crossing vessel. We
      highlight noteworthy features of the clinical presentation and surgical repair. 

PMID- 26221563
TI  - Posthospital Discharge Medical Care Costs and Family Burden Associated with
      Osteoporotic Fracture Patients in China from 2011 to 2013.
AB  - Objectives. This study collected and evaluated data on the costs of outpatient
      medical care and family burden associated with osteoporosis-related fracture
      rehabilitation following hospital discharge in China. Materials and Methods. Data
      were collected using a patient questionnaire from osteoporosis-related fracture
      patients (N = 123) who aged 50 years and older who were discharged between
      January 2011 and January 2013 from 3 large hospitals in China. The survey
      captured posthospital discharge direct medical costs, indirect medical costs,
      lost work time for caregivers, and patient ambulatory status. Results. Hip
      fracture was the most frequent fracture site (62.6%), followed by vertebral
      fracture (34.2%). The mean direct medical care costs per patient totaled 3,910Y,
      while mean indirect medical costs totaled 743Y. Lost work time for unpaid family
      caregivers was 16.4 days, resulting in an average lost income of 3,233Y. The
      average posthospital direct medical cost, indirect medical cost, and caregiver
      lost income associated with a fracture patient totaled 7,886Y. Patients'
      ambulatory status was negatively impacted following fracture. Conclusions.
      Significant time and cost of care are placed on patients and caregivers during
      rehabilitation after discharge for osteoporotic fracture. It is important to
      evaluate the role and responsibility for creating the growing and inequitable
      burden placed on patients and caregivers following osteoporotic fracture. 

PMID- 26221564
TI  - Quality Degradation of Chinese White Lotus Seeds Caused by Dampening during
      Processing and Storage: Rapid and Nondestructive Discrimination Using Near
      Infrared Spectroscopy.
AB  - Dampening during processing or storage can largely influence the quality of white
      lotus seeds (WLS). This paper investigated the feasibility of using near-infrared
      (NIR) spectroscopy and chemometrics for rapid and nondestructive discrimination
      of the dampened WLS. Regular (n = 167) and dampened (n = 118) WLS objects were
      collected from five main producing areas and NIR reflectance spectra (4000-12000
      cm(-1)) were measured for bare kernels. The influence of spectral preprocessing
      methods, including smoothing, taking second-order derivatives (D2), and standard
      normal variate (SNV), on partial least squares discrimination analysis (PLSDA)
      was compared to select the optimal data preprocessing method. A moving-window
      strategy was combined with PLSDA (MWPLSDA) to select the most informative
      wavelength intervals for classification. Based on the selected spectral ranges,
      the sensitivity, specificity, and accuracy were 0.927, 0.950, and 0.937 for SNV
      MWPLSDA, respectively. 

PMID- 26221565
TI  - Effects of Salvadora persica Extract on the Hematological and Biochemical
      Alterations against Immobilization-Induced Rats.
AB  - A total of 24 rats were divided into 4 groups: control, stress, extract alone,
      and stress + extract (n = 6 each), for total 21 days of treatment. The
      immobilization stress was induced in rats by putting them in 20 cm * 7 cm plastic
      tubes for 2 h/day for 21 days. Rats were postorally treated with Salvadora
      persica at a dose of 900 mg/kg body weight via intragastric intubations. At the
      end of the test period, hematological and biochemical parameters were determined
      in blood and serum samples with determination of vital organs weights. The vital
      organ weights were not significantly affected in stressed rats as compared to
      control rats. Compared to the control group, the stress treated group showed
      significances in several hematological parameters, including decreases in WBC,
      RBC, and PLT counts. Furthermore, in comparison to the control group, the stress
      group showed significantly increased blood glucose, serum total cholesterol, LDL
      cholesterol, and triacylglycerols levels and decreased HDL-cholesterol level. The
      hematological and biochemical parameters in the stress + extract treated group
      were approximately similar to control group. The SP extract restored the changes
      observed following stress treatment. 

PMID- 26221566
TI  - Confocal fluorescence microscopy: An ultra-sensitive tool used to evaluate
      intracellular antiretroviral nano-drug delivery in HeLa cells.
AB  - In the last decade, confocal fluorescence microscopy has emerged as an ultra
      sensitive tool for real-time study of nanoparticles (NPs) fate at the cellular
      level. According to WHO 2007 report, Human Immunodeficiency Virus/Acquired
      Immunodeficiency Syndrome (HIV/AIDS) is still one of the world's major health
      threats by claiming approximately 7,000 new infections daily worldwide. Although
      combination antiretroviral drugs (cARV) therapy has improved the life-expectancy
      of HIV-infected patients, routine use of high doses of cARV has serious health
      consequences and requires complete adherence to the regimen for success. Thus,
      our research goal is to fabricate long-acting novel cARV loaded poly(lactide-co
      glycolic acid) (PLGA) nanoparticles (cARV-NPs) as drug delivery system. However,
      important aspects of cARV-NPs that require special emphasis are their cellular
      uptake, potency, and sustained drug release efficiency over-time. In this
      article, ultra-sensitive confocal microscopy is been used to evaluate the uptake
      and sustained drug release kinetics of cARV-NPs in HeLa cells. To evaluate with
      the above goal, instead of cARV-drug, Rhodamine6G dye (fluorescent dye) loaded
      NPs (Rho6G NPs) have been formulated. To correlate the Rhodamin6G release
      kinetics with the ARV release from NPs, a parallel HPLC study was also performed.
      The results obtained indicate that Rho6G NPs were efficiently taken up at low
      concentration (<500 ng/ml) and that release was sustained for a minimum of 4 days
      of treatment. Therefore, high drug assimilation and sustained release properties
      of PLGA-NPs make them an attractive vehicle for cARV nano-drug delivery with the
      potential to reduce drug dosage as well as the number of drug administrations per
      month.

PMID- 26221567
TI  - Frozen moments: flashback memories of critical incidents in emergency personnel.
AB  - BACKGROUND: Emergency Department personnel regularly face highly stressful
      situations or critical incidents (CIs) that may subsequently be recalled as
      unbidden intrusive memories. In their most extreme form, such memories are
      reexperienced as if they were happening again in the present, as flashbacks. This
      study examined (1) which CIs are associated with flashback memories; (2)
      candidate person and work-related features that predict flashback memories; and
      (3) the association between flashback memories and anxiety, depression, and
      emotional exhaustion. METHODS: Emergency nurses (N = 91; 80.2% female) were
      recruited from two urban teaching hospitals and filled in self-report
      questionnaires. RESULTS: A majority (n = 59, 65%) experienced intrusive memories;
      almost half of the sample reported that their memories had flashback character.
      Those involved in resuscitations in the past week were at a fourfold risk for
      experiencing flashbacks. Having worked more consecutive days without taking time
      off was associated with a somewhat lower incidence of flashbacks. Moreover, older
      individuals who reported more work-related conflicts were at greater risk for
      experiencing flashback memories than their younger colleagues with heightened
      work conflict and flashback memory scores, respectively. Flashback memories were
      associated with heightened symptoms of anxiety, depression, and emotional
      exhaustion. CONCLUSIONS: The present findings have implications for evidence
      based health promotion in emergency personnel and other individuals regularly
      exposed to CIs.

PMID- 26221568
TI  - Left hippocampus-amygdala complex macro- and microstructural variation is
      associated with BDNF plasma levels in healthy elderly individuals.
AB  - INTRODUCTION: Deep brain gray matter (GM) structures are involved in several
      neurodegenerative disorders and are affected by aging. In this study, we
      investigated the potential relationship between levels of brain-derived
      neurotrophic factor (BDNF), a putative biomarker of age- and clinically relevant
      brain dysfunctions, and the presence of structural modifications that were
      evaluated by magnetic resonance imaging in six deep GM structures. METHODS:
      Volume changes and diffusion tensor imaging (DTI) scalars were studied in the
      thalamus, putamen, hippocampus, caudate nucleus, amygdala and pallidum of a
      cohort of 120 healthy subjects. The cohort included young (18-39 years old),
      adult (40-59 years old) and elderly (60-76 years old) subjects. RESULTS: No
      correlations were seen in the young and adult cohorts. In the elderly group, we
      observed reduced BDNF levels that correlated with increased DTI-based mean
      diffusivity occurring in the left hippocampus along with decreased normalized
      volume in the left amygdala. CONCLUSIONS: These findings suggest that, in elderly
      subjects, BDNF may exert regional and lateralized effects that allow the
      integrity of two strategic deep GM areas such as the hippocampus and the
      amygdala.

PMID- 26221569
TI  - Relative brain signature: a population-based feature extraction procedure to
      identify functional biomarkers in the brain of alcoholics.
AB  - BACKGROUND: A novel feature extraction technique, Relative-Brain-Signature (RBS),
      which characterizes subjects' relationship to populations with distinctive
      neuronal activity, is presented. The proposed method transforms a set of
      Electroencephalography's (EEG) time series in high dimensional space to a space
      of fewer dimensions by projecting time series onto orthogonal subspaces. METHODS:
      We apply our technique to an EEG data set of 77 abstinent alcoholics and 43
      control subjects. To characterize subjects' relationship to the alcoholic and
      control populations, one RBS vector with respect to the alcoholic and one with
      respect to the control population is constructed. We used the extracted RBS
      vectors to identify functional biomarkers over the brain of alcoholics. To
      achieve this goal, the classification algorithm was used to categorize subjects
      into alcoholics and controls, which resulted in 78% accuracy. RESULTS AND
      CONCLUSIONS: Using the results of the classification, regions with distinctive
      functionality in alcoholic subjects are detected. These affected regions, with
      respect to their spatial extent, are frontal, anterior frontal, centro-parietal,
      parieto-occiptal, and occipital lobes. The distribution of these regions over the
      scalp indicates that the impact of the alcohol in the cerebral cortex of the
      alcoholics is spatially diffuse. Our finding suggests that these regions engage
      more of the right hemisphere relative to the left hemisphere of the alcoholics'
      brain.

PMID- 26221570
TI  - Application of ICA to realistically simulated (1)H-MRS data.
AB  - INTRODUCTION: (1)H-MRS signals from brain tissues capture information on in vivo
      brain metabolism and neuronal biomarkers. This study aims to advance the use of
      independent component analysis (ICA) for spectroscopy data by objectively
      comparing the performance of ICA and LCModel in analyzing realistic data that
      mimics many of the known properties of in vivo data. METHODS: This work
      identifies key features of in vivo (1)H-MRS signals and presents methods to
      simulate realistic data, using a basis set of 12 metabolites typically found in
      the human brain. The realistic simulations provide a much needed ground truth to
      evaluate performances of various MRS analysis methods. ICA is applied to
      collectively analyze multiple realistic spectra and independent components
      identified with our generative model to obtain ICA estimates. These same data are
      also analyzed using LCModel and the comparisons between the ground-truth and the
      analysis estimates are presented. The study also investigates the potential
      impact of modeling inaccuracies by incorporating two sets of model resonances in
      simulations. RESULTS: The simulated fid signals incorporating line broadening,
      noise, and residual water signal closely resemble the in vivo signals. Simulation
      analyses show that the resolution performances of both LCModel and ICA are not
      consistent across metabolites and that while ICA resolution can be improved for
      certain resonances, ICA is as effective as, or better than, LCModel in resolving
      most model resonances. CONCLUSION: The results show that ICA can be an effective
      tool in comparing multiple spectra and complements existing approaches for
      providing quantified estimates.

PMID- 26221571
TI  - Repetitive speech elicits widespread deactivation in the human cortex: the
      "Mantra" effect?
AB  - BACKGROUND: Mantra (prolonged repetitive verbal utterance) is one of the most
      universal mental practices in human culture. However, the underlying neuronal
      mechanisms that may explain its powerful emotional and cognitive impact are
      unknown. In order to try to isolate the effect of silent repetitive speech, which
      is used in most commonly practiced Mantra meditative practices, on brain
      activity, we studied the neuronal correlates of simple repetitive speech in
      nonmeditators - that is, silent repetitive speech devoid of the wider context and
      spiritual orientations of commonly practiced meditation practices. METHODS: We
      compared, using blood oxygenated level-dependent (BOLD) functional magnetic
      resonance imaging (fMRI), a simple task of covertly repeating a single word to
      resting state activity, in 23 subjects, none of which practiced meditation
      before. RESULTS: We demonstrate that the repetitive speech was sufficient to
      induce a widespread reduction in BOLD signal compared to resting baseline. The
      reduction was centered mainly on the default mode network, associated with
      intrinsic, self-related processes. Importantly, contrary to most cognitive tasks,
      where cortical-reduced activation in one set of networks is typically
      complemented by positive BOLD activity of similar magnitude in other cortical
      networks, the repetitive speech practice resulted in unidirectional negative
      activity without significant concomitant positive BOLD. A subsequent behavioral
      study showed a significant reduction in intrinsic thought processes during the
      repetitive speech condition compared to rest. CONCLUSIONS: Our results are
      compatible with a global gating model that can exert a widespread induction of
      negative BOLD in the absence of a corresponding positive activation. The
      triggering of a global inhibition by the minimally demanding repetitive speech
      may account for the long-established psychological calming effect associated with
      commonly practiced Mantra-related meditative practices.

PMID- 26221572
TI  - Acute anoxic changes in peripheral nerve: anatomic and physiologic correlations.
AB  - INTRODUCTION: The response of the peripheral nerve to anoxia is modulated by many
      factors including glucose and temperature. The purposes of this article are to
      demonstrate the effects of these factors on the pathological changes induced by
      anoxia and to compare the electrophysiologic changes and pathological changes in
      the same nerves. METHODS: Sciatic nerves were harvested from rats and placed in a
      perfusion apparatus where neurophysiologic responses could be recorded
      continuously during a 16 h experiment. After the experiment, light microscopy and
      electron microscopy were performed. RESULTS: Light microscopic images showed mild
      changes from anoxia at normoglycemia. Hypoglycemic anoxia produced massive axonal
      swelling while hyperglycemic anoxia produced apparent changes in the myelin.
      Anoxic changes were not uniform in all axons. Electron microscopy showed only
      minor disruptions of the cytoskeleton with anoxia during normoglycemia. At the
      extremes of glucose concentration especially with hyperglycemia, there was a more
      severe disruption of intermediate filaments and loss of axonal structure with
      anoxia. Hypothermia protected axons from the effect of anoxia and produced peak
      axonal swelling in the 17-30 degrees C range. CONCLUSIONS: The combination of
      hyperglycemia or hypoglycemia and anoxia produces extremely severe axonal
      disruption. Changes in axonal diameter are complex and are influenced by many
      factors.

PMID- 26221573
TI  - Striatal activity and reduced white matter increase frontal activity in youths
      with family histories of alcohol and other substance-use disorders performing a
      go/no-go task.
AB  - INTRODUCTION: Youths with a family history of alcohol and other drug use
      disorders (FH+) are at greater risk of developing substance-use disorders
      relative to those with no such family histories (FH-). We previously reported
      that FH+ youths have elevated activity in the supplementary motor area (SMA) and
      dorsal striatum while performing go/no-go tasks and have reduced frontal white
      matter integrity. A better understanding of relationships between these variables
      would provide insight into how frontostriatal circuitry is altered in FH+ youths,
      which may be an important contributor to their elevated risk. METHODS: In this
      study, we used structural equation modeling (SEM) to test interactions between
      activity in the SMA and dorsal striatum in 72 FH+ and 32 FH- youths during go/no
      go task performance and to determine whether increased activity in these regions
      in FH+ youths can be at least partially explained by reduced frontal white matter
      integrity, as indexed by anterior corona radiata fractional anisotropy and N
      acetylaspartate. RESULTS: Increased dorsal striatum activity explained most
      (?75%) of the elevated SMA activity in FH+ youths, and the combined contributions
      of increased dorsal striatal activity, and decreased white matter integrity fully
      explained the elevated SMA activity. CONCLUSIONS: These results suggest the
      elevated frontal cortical activity in FH+ youths is driven both by their
      increased striatal activity via downstream projections and reduced white matter
      integrity in frontal cortical projections, the latter likely increasing frontal
      cortical activity due to increased energy demands required for action potential
      propagation. As part of our ongoing longitudinal studies we will examine how
      these frontostriatal alterations relate to risk for developing substance-use
      disorders.

PMID- 26221576
TI  - In vivo dose response and in vitro mechanistic analysis of enhanced
      immunoglobulin A production by Lactobacillus plantarum AYA.
AB  - Secretory immunoglobulin A (IgA) mediates the mucosal immune system, which
      provides the first line of defense against inhaled and ingested pathogenic
      bacteria and viruses. Lactobacillus plantarum AYA increases the IgA level of
      Peyer's patch (PP) cells, but the recommended amount of consumption and the
      mechanism of action remains unclear. Better understanding of these is essential
      to development of L. plantarum AYA for use in functional foods. Therefore, we
      investigated the dose-response effect (in vivo) and mechanism (in vitro) of IgA
      enhancement induced by L. plantarum AYA. In the small intestine of the mice fed a
      diet containing 0.03% or 0.3% of L. plantarum AYA powder for 4 weeks, the IgA
      levels were significantly increased. Thus, it is suggested that the recommended
      amount of consumption of L. plantarum AYA is about 0.72 mg per day. In addition,
      the bacterial cell wall fraction significantly enhanced the IgA production level
      of murine PP cells in the in vitro assay. The ability of whole cells and the cell
      wall fraction to enhance IgA levels was significantly inhibited by an anti-Toll
      like receptor-2 (TLR-2) antibody, which suggests that the cell wall fraction of
      L. plantarum AYA increases the IgA level via TLR-2. These findings indicate that
      L. plantarum AYA is a potential functional food source that maintains mucosal
      immunity. 

PMID- 26221574
TI  - Assessment of chemotherapy-induced peripheral neuropathy using the LDIFLARE
      technique: a novel technique to detect neural small fiber dysfunction.
AB  - INTRODUCTION: The diagnosis and quantification of chemotherapy-induced peripheral
      neuropathy (CIPN) remains a challenge. Conventional methods including
      quantitative sensory testing (QST), nerve conduction tests, and biopsy are unable
      to detect subclinical changes, and do not consistently correlate with severity of
      patients' symptoms and functional impairment. This study aims to determine the
      utility of the LDI (laser Doppler imager) FLARE technique in the diagnosis of
      CIPN and whether it correlates with symptom severity. MATERIALS AND METHODS: We
      assessed 24 patients with established CIPN [12 due to platinum analogs (PA) and
      12 to Taxanes (TX)] and 24 matched healthy controls (HC). All underwent
      neurophysiological examination including vibration perception threshold (VPT),
      sural nerve amplitude (SNAP) and conduction velocity (SNCV), LDIFLARE, and
      fasting biochemistry. The QLQ-CIPN20 questionnaire was used to assess symptom
      severity. RESULTS: HC, combined chemotherapy (CG), PA , and TX groups were
      matched for age, sex, BMI, and blood pressure. The LDIFLARE was significantly
      reduced in CG compared to HC (P =< 0.0001), whereas SNAP (P = 0.058) and SNCV (P
      = 0.054) were not. The LDIFLARE correlated with the QLQ-CIPN20 symptom scores in
      all three categories namely, CG (P =< 0.0001), PA (P = 0.001) and TX (P = 0.027)
      whilst, VPT, SNAP, and SNCV did not. CONCLUSION: Our findings suggest that the
      LDIFLARE technique is more helpful in confirming the diagnosis of CIPN in
      patients with distal sensory symptoms than current commonly used methods.
      Moreover, this novel test fulfils the unmet need for a diagnostic test that
      relates to the severity of symptoms. This may be useful in quantifying early
      changes in small fibre function indicating early CIPN.

PMID- 26221577
TI  - Relationships among fecal daidzein metabolites, dietary habit and BMI in healthy
      volunteers: a preliminary study.
AB  - To investigate the relationships among fecal isoflavone metabolism, dietary habit
      and Body Mass Index (BMI), 15 healthy men and 15 healthy women were recruited and
      provided stool samples for analysis of ex vivo anaerobic incubation of fecal
      suspension with daidzein. A negative correlation was observed between BMI and the
      dihydrodaidzein (DHD) production in men, and between BMI and the equol production
      in women. There was a positive correlation between intake of soluble dietary
      fiber and the DHD production in men. The results suggest that dietary habits and
      BMI are related to the metabolic activity of isoflavonoids by fecal intestinal
      microbiota. 

PMID- 26221579
TI  - Combined effect of hydrogen sulphide donor and losartan in experimental diabetic
      nephropathy in rats.
AB  - BACKGROUND: Diabetic nephropathy (DN) is one of the complex complications of
      Diabetes Mellitus (DM). The present study has been designed to examine protective
      role of hydrogen Sulphide (H2S) donor against streptozotocin (STZ) -induced
      behavioral, oxidative abnormalities and its DN like symptoms in rats. METHODS:
      For the induction of DN single intraperitoneal administration of STZ (45 mg/kg)
      was given till third week. Behavioral parameters were measured on 1st, 7th, 21st
      and 42nd days and biochemical parameters were performed on 42nd day. All the drug
      treatments [NaHS (10 & 30 MUmol/kg i.p), DL-propargylglycine (10 mg/kg i.p),
      standard drug- Losartan (5 mg/kg p.o)] were given for 3 weeks staring from 21st
      day after the STZ injection. RESULTS: Three weeks treatment with sodium
      hydrosulphide (NaHS) (10 and 30 MUmol/kg i.p,) significantly attenuated the
      behavioral and biochemical abnormalities in STZ-treated animals. DL
      propargylglycine (10 mg/kg i.p) pretreatment with sub-effective dose of NaHS (30
      MUmol/kg i.p) significantly reversed the protective effect of NaHS. However,
      combination of both NaHS (30 MUmol/kg i.p) and standard drug losartan (5 mg/kg
      p.o) potentiated their effects as compared to their effect alone. CONCLUSION: The
      results of the present study suggest that H2S treatment showed significant
      improvement in behavioral and biochemical abnormalities induced by STZ
      administration. Thus H2S represents a target of treatment to prevent the
      progression of complications by DN.

PMID- 26221578
TI  - Use of miRNAs as biomarkers in sepsis.
AB  - Sepsis is one of the most common causes of death in critical patients. Severe
      generalized inflammation, infections, and severe physiological imbalances
      significantly decrease the survival rate with more than 50%. Moreover,
      monitoring, evaluation, and therapy management often become extremely difficult
      for the clinician in this type of patients. Current methods of diagnosing sepsis
      vary based especially on the determination of biochemical-humoral markers, such
      as cytokines, components of the complement, and proinflammatory and anti
      inflammatory compounds. Recent studies highlight the use of new biomarkers for
      sepsis, namely, miRNAs. miRNAs belong to a class of small, noncoding RNAs with an
      approximate content of 19-23 nucleotides. Following biochemical and physiological
      imbalances, the expression of miRNAs in blood or other body fluids changes
      significantly. Moreover, its stability, specificity, and selectivity make miRNAs
      ideal candidates for sepsis biomarkers. In conclusion, we can affirm that stable
      species of circulating miRNAs represent potential biomarkers for monitoring the
      evolution of sepsis. 

PMID- 26221580
TI  - Prevalence of depression among subjects with and without gestational diabetes
      mellitus in Bangladesh: a hospital based study.
AB  - BACKGROUND: Data on association between depression and diabetes during the
      pregnancy period in Asia, specifically in Bangladesh are scarce. The study was
      designed to measure the prevalence of depression during pregnancy with or without
      Gestational Diabetes Mellitus (GDM). METHODS: Seven hundred and forty eight
      pregnant women (382 with GDM, 366 without-GDM) attending at the Bangladesh
      Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic
      Disorders, participated in the study. Blood glucose was measured following both
      WHO and ACOG criteria; GDM was diagnosed within 24-28 weeks. Depressive symptoms
      were assessed following MADRS scale. Semi-structured questionnaire was used to
      record their socio-demographic status and clinical and family history. Blood
      pressure, height, weight were also measured. RESULTS: Overall prevalence of
      depression was 18.32 %. Depression was higher in GDM subjects (25.92 %) compared
      to without-GDM subjects (10.38 %) with mean age of of 28.34 and 27.17 years
      respectively. Prevalence of depression was alarming in both the extreme of age.
      Dwelling place (P < 0.009) and past history of GDM (P < 0.018) had strong
      association with Depression. Higher prevalence of depression was found in
      Primipara whereas the risk of GDM increased with parity. Other obstetrical
      factors did not show any significant association with depression and GDM. Income
      (self and total family), physical exercise, sedentary lifestyle and workload had
      no significant statistical association with depression or GDM. CONCLUSION: Higher
      rate of depression in pregnancy deserves medical attention especially women
      diagnosed with GDM. Further studies should estimate adverse pregnancy outcome for
      untreated depression especially in GDM cases.

PMID- 26221582
TI  - beta-Elemene Inhibits Cell Proliferation by Regulating the Expression and
      Activity of Topoisomerases I and IIalpha in Human Hepatocarcinoma HepG-2 Cells.
AB  - OBJECTIVE: To investigate the effects of beta-Elemene (beta-ELE) on the
      proliferation, apoptosis, and topoisomerase I (TOPO I) and topoisomerase IIalpha
      (TOPO IIalpha) expression and activity of human hepatocarcinoma HepG-2 cells.
      METHODS: After treatment with beta-ELE, morphological alterations of HepG-2 cells
      were observed under an inverted microscope. Cell proliferation was assessed using
      an MTT assay, cell cycles were analyzed using flow cytometry, and apoptosis was
      detected by Annexin V/PI staining. The expression of TOPO I and TOPO IIalpha was
      analyzed by Western blot techniques, and their activity was measured using the
      TOPO I-mediated, supercoiled pBR322 DNA relaxation and TOPO IIalpha-mediated
      Kinetoplast DNA (kDNA) decatenation assays, respectively. Supercoiled pBR322 and
      kDNA were also used to determine the direct effect of beta-ELE on DNA breaks.
      RESULTS: beta-ELE significantly inhibited HepG-2 cell proliferation in a dose-
      and time-dependent manner. beta-ELE also induced tumor cell arrest at S phase,
      induced cell apoptosis, and downregulated the protein expression of TOPO I and
      TOPO IIalpha in a dose-dependent manner. beta-ELE also inhibited TOPO I- and TOPO
      IIalpha-mediated DNA relaxation but did not directly induce DNA breakage at any
      concentration. CONCLUSION: beta-ELE could inhibit the proliferation of HepG-2
      cells and interfere with the expression and activity of TOPO I and TOPO IIalpha.

PMID- 26221581
TI  - Update on the Pathogenic Implications and Clinical Potential of microRNAs in
      Cardiac Disease.
AB  - miRNAs, a unique class of endogenous noncoding RNAs, are highly conserved across
      species, repress gene translation upon binding to mRNA, and thereby influence
      many biological processes. As such, they have been recently recognized as
      regulators of virtually all aspects of cardiac biology, from the development and
      cell lineage specification of different cell populations within the heart to the
      survival of cardiomyocytes under stress conditions. Various miRNAs have been
      recently established as powerful mediators of distinctive aspects in many cardiac
      disorders. For instance, acute myocardial infarction induces cardiac tissue
      necrosis and apoptosis but also initiates a pathological remodelling response of
      the left ventricle that includes hypertrophic growth of cardiomyocytes and
      fibrotic deposition of extracellular matrix components. In this regard, recent
      findings place various miRNAs as unquestionable contributing factors in the
      pathogenesis of cardiac disorders, thus begging the question of whether miRNA
      modulation could become a novel strategy for clinical intervention. In the
      present review, we aim to expose the latest mechanistic concepts regarding miRNA
      function within the context of CVD and analyse the reported roles of specific
      miRNAs in the different stages of left ventricular remodelling as well as their
      potential use as a new class of disease-modifying clinical options. 

PMID- 26221583
TI  - The Role of Magnetic Resonance Imaging and Cardiac Computed Tomography in the
      Assessment of Left Atrial Anatomy, Size, and Function.
AB  - In the last decade, there has been increasing evidence that comprehensive
      evaluation of the left atrium is of utmost importance. Numerous studies have
      clearly demonstrated the prognostic value of left atrial volume for long-term
      outcome. Furthermore, advances in catheter ablation procedures used for the
      treatment of drug-refractory atrial fibrillation require the need for detailed
      knowledge of left atrial and pulmonary venous morphology as well of atrial wall
      characteristics. This review article discusses the role of cardiac magnetic
      resonance and computed tomography in assessment of left atrial size, its normal
      and abnormal morphology, and function. Special interest is paid to the utility of
      these rapidly involving noninvasive imaging methods before and after atrial
      fibrillation ablation. 

PMID- 26221584
TI  - A MicroRNA-Transcription Factor Blueprint for Early Atrial Arrhythmogenic
      Remodeling.
AB  - Spontaneous self-terminating atrial fibrillation (AF) is one of the most common
      heart rhythm disorders, yet the regulatory molecular mechanisms underlying this
      syndrome are rather unclear. MicroRNA (miRNA) transcriptome and expression of
      candidate transcription factors (TFs) with potential roles in arrhythmogenesis,
      such as Pitx2, Tbx5, and myocardin (Myocd), were analyzed by microarray, qRT-PCR,
      and Western blotting in left atrial (LA) samples from pigs with transitory AF
      established by right atrial tachypacing. Induced ectopic tachyarrhythmia caused
      rapid and substantial miRNA remodeling associated with a marked downregulation of
      Pitx2, Tbx5, and Myocd expression in atrial myocardium. The downregulation of
      Pitx2, Tbx5, and Myocd was inversely correlated with upregulation of the
      corresponding targeting miRNAs (miR-21, miR-10a/10b, and miR-1, resp.) in the LA
      of paced animals. Through in vitro transient transfections of HL-1 atrial
      myocytes, we further showed that upregulation of miR-21 did result in
      downregulation of Pitx2 in cardiomyocyte background. The results suggest that
      immediate-early miRNA remodeling coupled with deregulation of TF expression
      underlies the onset of AF. 

PMID- 26221585
TI  - Effectiveness of the First Dose of BCG against Tuberculosis among HIV-Infected,
      Predominantly Immunodeficient Children.
AB  - The objective of this study was to estimate the protective effect of Bacille
      Calmette-Guerin (BCG) vaccine against tuberculosis among (predominantly
      immunodeficient) HIV-infected children in Angola. A hospital-based case-control
      study was conducted with 230 cases, children coinfected with tuberculosis, and
      672 controls, HIV-infected children from the same hospital, aged 18 months to 13
      years. The presence of a vaccination scar was taken as a proxy marker for BCG
      vaccination. The crude effectiveness was 8% (95% CI: -26 to 32) and the adjusted
      effectiveness was 30% (95% CI: -75 to 72). The present study suggests that BCG
      does not have a protective effect against tuberculosis among immunodeficient HIV
      infected children. Since BCG is no longer given to HIV-infected children, the
      study may not be replicated. Accepting that these findings should be considered
      with caution, they are nonetheless likely to be the last estimate of BCG efficacy
      in a sufficiently powered study. 

PMID- 26221586
TI  - Surgical Left Atrial Appendage Exclusion Does Not Impair Left Atrial Contraction
      Function: A Pilot Study.
AB  - BACKGROUND: In order to reduce stroke risk, left atrial appendage amputation
      (LAAA) is widely adopted in recent years. The effect of LAAA on left atrial (LA)
      function remains unknown. The objective of present study was to assess the effect
      of LAAA on LA function. METHODS: Sixteen patients with paroxysmal AF underwent
      thoracoscopic, surgical PVI with LAAA (LAAA group), and were retrospectively
      matched with 16 patients who underwent the same procedure without LAA amputation
      (non-LAAA group). To objectify LA function, transthoracic echocardiography with
      2D Speckle Tracking was performed before surgery and at 12 months follow-up.
      RESULTS: Mean age was 57 +/- 9 years, 84% were male. Baseline characteristics did
      not differ significantly except for systolic blood pressure (p = 0.005). In both
      groups, the contractile LA function and LA ejection fraction were not
      significantly reduced. However, the conduit and reservoir function were
      significantly decreased at follow-up, compared to baseline. The reduction of
      strain and strain rate was not significantly different between groups.
      CONCLUSIONS: In this retrospective, observational matched group comparison with a
      convenience sample size of 16 patients, findings suggest that LAAA does not
      impair the contractile LA function when compared to patients in which the
      appendage was unaddressed. However, the LA conduit and reservoir function are
      reduced in both the LAAA and non-LAAA group. Our data suggest that the LAA can be
      removed without late LA functional consequences.

PMID- 26221587
TI  - Alendronate-Eluting Biphasic Calcium Phosphate (BCP) Scaffolds Stimulate
      Osteogenic Differentiation.
AB  - Biphasic calcium phosphate (BCP) scaffolds have been widely used in orthopedic
      and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are
      not satisfactory for the stimulation of osteogenic differentiation and
      maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN
      ) eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by
      scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy
      (EDS), and attenuated total reflectance-Fourier transform infrared spectroscopy
      (ATR-FTIR). An in vitro release study showed that release of ALN from ALN-eluting
      BCP scaffolds was sustained for up to 28 days. In vitro results revealed that MG
      63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and
      calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN
      compared with the BCP scaffold alone. Therefore, this study suggests that ALN
      eluting BCP scaffolds have the potential to effectively stimulate osteogenic
      differentiation. 

PMID- 26221588
TI  - The Role of Epigenetics in Arterial Calcification.
AB  - Arterial calcification is highly prevalent and correlated with cardiovascular
      mortality, especially in patients with ESRD or diabetes. The pathogenesis of
      arterial calcification is multifactorial, with both genetic and environmental
      factors being implicated. In recent years, several mechanisms contributing to
      arterial calcification have been proposed. However, these can only explain a
      small proportion of the variability in arterial calcification, which is a major
      obstacle for its prevention and management. Epigenetics has emerged as one of the
      most promising areas that may fill in some of the gaps in our current knowledge
      of the interaction between the environmental insults with gene regulation in the
      development of diseases. Epigenetics refers to heritable and acquired changes in
      gene transcription that occur independently of the DNA sequence. Well-known
      components of epigenetic regulation include DNA methylation, histone
      modifications, and microRNAs. Epigenetics research in the regulation of arterial
      calcification has only recently been elucidated. In this review, we will
      summarise recent progress in epigenetic pathways involved in arterial
      calcification and discuss potential therapeutic interventions based on epigenetic
      mechanisms. 

PMID- 26221590
TI  - Antioxidative Role of Hatikana (Leea macrophylla Roxb.) Partially Improves the
      Hepatic Damage Induced by CCl4 in Wistar Albino Rats.
AB  - This research investigated the protective role of Leea macrophylla extract on
      CCl4-induced acute liver injury in rats. Different fractions of Leea macrophylla
      (Roxb.) crude extract were subjected to analysis for antioxidative effects. Rats
      were randomly divided into four groups as normal control, hepatic control, and
      reference control (silymarin) group and treatment group. Evaluations were made
      for the effects of the fractions on serum enzymes and biochemical parameters of
      CCl4-induced albino rat. Histopathological screening was also performed to
      evaluate the changes of liver tissue before and after treatment. Different
      fractions of Leea macrophylla showed very potent 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical scavenging effect, FeCl3 reducing effect, superoxide scavenging
      effect, and iron chelating effect. Carbon tetrachloride induction increased the
      level of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      and alkaline phosphatase (ALP) and other biochemical parameters such as lipid
      profiles, total protein, and CK-MB. In contrast, treatment of Leea macrophylla
      reduced the serum aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), and alkaline phosphatase (ALP) activities as well as biochemical
      parameters activities. L. macrophylla partially restored the lipid profiles,
      total protein, and CK-MB. Histopathology showed the treated liver towards
      restoration. Results evidenced that L. macrophylla can be prospective source of
      hepatic management in liver injury. 

PMID- 26221591
TI  - Advances in Diagnostic Imaging Technologies to Evaluate the Retina and the Optic
      Disc.

PMID- 26221589
TI  - Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling.
AB  - A cluster of miR-221/222 is a key player in vascular biology through exhibiting
      its effects on vascular smooth muscle cells (VSMCs) and endothelial cells (ECs).
      These miRNAs contribute to vascular remodeling, an adaptive process involving
      phenotypic and behavioral changes in vascular cells in response to vascular
      injury. In proliferative vascular diseases such as atherosclerosis, pathological
      vascular remodeling plays a prominent role. The miR-221/222 cluster controls
      development and differentiation of ECs but inhibits their proangiogenic
      activation, proliferation, and migration. miR-221/222 are primarily implicated in
      maintaining endothelial integrity and supporting quiescent EC phenotype. Vascular
      expression of miR-221/222 is upregulated in initial atherogenic stages causing
      inhibition of angiogenic recruitment of ECs and increasing endothelial
      dysfunction and EC apoptosis. In contrast, these miRNAs stimulate VSMCs and
      switching from the VSMC "contractile" phenotype to the "synthetic" phenotype
      associated with induction of proliferation and motility. In atherosclerotic
      vessels, miR-221/222 drive neointima formation. Both miRNAs contribute to
      atherogenic calcification of VSMCs. In advanced plaques, chronic inflammation
      downregulates miR-221/222 expression in ECs that in turn could activate
      intralesion neoangiogenesis. In addition, both miRNAs could contribute to
      cardiovascular pathology through their effects on fat and glucose metabolism in
      nonvascular tissues such as adipose tissue, liver, and skeletal muscles. 

PMID- 26221592
TI  - miR-27 and miR-125 Distinctly Regulate Muscle-Enriched Transcription Factors in
      Cardiac and Skeletal Myocytes.
AB  - MicroRNAs are noncoding RNAs of approximately 22-24 nucleotides which are capable
      of interacting with the 3' untranslated region of coding RNAs (mRNAs), leading to
      mRNA degradation and/or protein translation blockage. In recent years,
      differential microRNA expression in distinct cardiac development and disease
      contexts has been widely reported, yet the role of individual microRNAs in these
      settings remains largely unknown. We provide herein evidence of the role of miR
      27 and miR-125 regulating distinct muscle-enriched transcription factors.
      Overexpression of miR-27 leads to impair expression of Mstn and Myocd in HL1
      atrial cardiomyocytes but not in Sol8 skeletal muscle myoblasts, while
      overexpression of miR-125 resulted in selective upregulation of Mef2d in HL1
      atrial cardiomyocytes and downregulation in Sol8 cells. Taken together our data
      demonstrate that a single microRNA, that is, miR-27 or miR-125, can selectively
      upregulate and downregulate discrete number of target mRNAs in a cell-type
      specific manner. 

PMID- 26221593
TI  - Novel Anticoagulants in Atrial Fibrillation: Monitoring, Reversal and
      Perioperative Management.
AB  - Atrial fibrillation continues to be a significant source of morbidity and
      mortality worldwide. Effective anticoagulation remains the cornerstone of
      outpatient and inpatient treatment. The use of the new generation of
      anticoagulants (NOACs) continues to grow. Recently published data indicate their
      cost-effectiveness and overall safety in stroke prevention; compared to vitamin K
      antagonists, they can be prescribed in fixed doses for long-term therapy without
      the need for coagulation monitoring. Both United States and European Guidelines
      recommend NOACs for stroke prevention in patients with atrial fibrillation. This
      review discusses each of the NOACs, along with their efficacy and safety data. It
      explores the most recent guidelines regarding their perioperative use in atrial
      fibrillation patients. It also discusses bleeding complications, perioperative
      management, and reversal agents. 

PMID- 26221594
TI  - The Genetic Deletion of 6q21 and PRDM1 and Clinical Implications in Extranodal
      NK/T Cell Lymphoma, Nasal Type.
AB  - 6q21 genetic deletion has been frequently detected in extranodal NK/T cell
      lymphoma, nasal type (EN-NK/T-NT), and PRDM1 is considered as candidate gene.
      However, direct detection of PRDM1 deletion has not been well documented. We
      investigated genetic alterations of 6q21 and PRDM1 in 43 cases of EN-NK/T-NT and
      cell lines by FISH. PRDM1 expression was evaluated by immunohistochemistry and
      Western blot. The correlation between genetic alteration and PRDM1 expression and
      the significance in clinic-pathologic were analyzed. Heterozygous deletion of
      6q21 and/or PRDM1 was observed in 24 of 43 cases (55.81%) of EN-NK/T-NT including
      16 cases (37.21%) for 6q21 deletion and 19 cases (44.19%) for PRDM1 deletion.
      Similarly, heterozygous codeletion of 6q21 and PRDM1 was identified in NK92 and
      NKL cells. The heterozygous deletion of 6q21 and/or PRDM1 was correlated with
      PRDM1 expression. However, genetic deletion of 6q21 and/or PRDM1 was not
      correlated with clinicopathological features of EN-NK/T-NT, while PRDM1
      expression showed positive effect on the outcome of patients as those as disease
      site, B symptom, and clinical stage. Thus, heterozygous deletion of 6q21 and/or
      PRDM1 was frequently detected in EN-NK/T-NT and correlated with downregulation of
      PRDM1. But the prognostic role of genetic deletion needs to be further evaluated
      in larger cohort. 

PMID- 26221595
TI  - miR-126 Is Involved in Vascular Remodeling under Laminar Shear Stress.
AB  - Morphology and changes in gene expression of vascular endothelium are mainly due
      to shear stress and inflammation. Cell phenotype modulation has been clearly
      demonstrated to be controlled by small noncoding micro-RNAs (miRNAs). This study
      focused on the effect of laminar shear stress (LSS) on human endothelial cells
      (HUVECs), with an emphasis on the role of miRNA-126 (miR-126). Exposure of HUVECs
      in vitro to LSS modified the shape of HUVECs and concomitantly regulated the
      expression of miR-126, vascular cell adhesion molecule 1 (VCAM-1), and syndecan-4
      (SDC-4). A significant upregulation of miR-126 during long-term exposure to flow
      was shown. Interestingly, LSS enhanced SDC-4 expression on the HUVEC membranes.
      Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell
      derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16,
      CXCR4, and SDC-4. No significant difference in terms of cell proliferation and
      apoptosis was observed between scramble, anti-miR-126, and pre-miR-126
      transfected HUVECs. In Apo-E KO/CKD mice aortas expressing a high level of miR
      126, SDC-4 was concomitantly increased. In conclusion, our results suggest that
      miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and
      downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4
      expression. 

PMID- 26221596
TI  - Role of Exogenous Hsp72 on Liver Dysfunction during Sepsis.
AB  - This study examined the role of exogenous heat shock protein 72 (Hsp72) in
      reversing sepsis-induced liver dysfunction. Sepsis was induced by cecal ligation
      and puncture. Liver function was determined on the basis of the enzymatic
      activities of serum glutamate oxaloacetate transaminase (GOT) and glutamate
      pyruvate transaminase (GPT). Apoptosis was determined using terminal
      deoxynucleotidyl transferase dUTP nick end labeling staining. B-cell lymphoma 2
      (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and
      cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed
      using Western blotting. Results showed GOT and GPT levels increased during
      sepsis, and levels were restored following the administration of human
      recombinant Hsp72 (rhHsp72). Increased liver tissue apoptosis was observed during
      sepsis, and normal apoptosis resumed on rhHsp72 administration. The Bcl-2/Bax
      ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver
      tissues were upregulated during sepsis and normalized after rhHsp72 treatment. We
      conclude that, during sepsis, exogenous Hsp72 restored liver dysfunction by
      inhibiting apoptosis via the mitochondria-initiated caspase pathway. 

PMID- 26221597
TI  - Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer
      Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of
      Chronic Kidney Failure.
AB  - Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23)
      levels are associated with cardiovascular disease in chronic renal disease. This
      study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based
      phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se),
      on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH)
      concentrations, and the development of vascular calcification in adenine-induced
      chronic renal failure (CRF) rats. After induction of CRF, renal function was
      significantly impaired in all groups: uremic rats developed severe
      hyperphosphatemia, and serum iPTH increased significantly. All uremic rats
      (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia
      and increased serum iPTH were controlled to a similar extent in all phosphate
      binder-treatment groups. Only sucroferric oxyhydroxide was associated with
      significantly decreased FGF23. Vascular calcifications of the thoracic aorta were
      decreased by all three phosphate binders. Calcifications were better prevented at
      the superior part of the thoracic and abdominal aorta in the PA21 treated rats.
      In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and
      Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular
      calcifications. The role of FGF23 in calcification remains to be confirmed. 

PMID- 26221598
TI  - MicroRNA-143/-145 in Cardiovascular Diseases.
AB  - MicroRNAs (miRNAs) play an essential role in the onset and development of many
      cardiovascular diseases. Increasing evidence shows that miRNAs can be used as
      potential diagnostic biomarkers for cardiovascular diseases, and miRNA-based
      therapy may be a promising therapy for the treatment of cardiovascular diseases.
      The microRNA-143/-145 (miR-143/-145) cluster is essential for differentiation of
      vascular smooth muscle cells (VSMCs) and determines VSMC phenotypic switching. In
      this review, we summarize the recent progress in knowledge concerning the
      function of miR-143/-145 in the cardiovascular system and their role in
      cardiovascular diseases. We discuss the potential role of miR-143/-145 as
      valuable biomarkers for cardiovascular diseases and explore the potential
      strategy of targeting miR-143 and miR-145. 

PMID- 26221599
TI  - Cardiomyocyte Remodeling in Atrial Fibrillation and Hibernating Myocardium:
      Shared Pathophysiologic Traits Identify Novel Treatment Strategies?
AB  - Atrial fibrillation (AF) is the most common arrhythmia and is associated with a
      high risk of morbidity and mortality. However, there are limited treatment
      strategies for prevention of disease onset and progression. Development of novel
      therapies for primary and secondary prevention of AF is critical and requires
      improved understanding of the cellular and molecular mechanisms underlying the AF
      disease process. Translational and clinical studies conducted over the past
      twenty years have revealed that atrial remodeling in AF shares several important
      pathophysiologic traits with the remodeling processes exhibited by hibernating
      myocardium that develop in response to chronic ischemia. These shared features,
      which include an array of structural, metabolic, and electrophysiologic changes,
      appear to represent a conserved adaptive myocyte response to chronic stress that
      involves dedifferentiation towards a fetal phenotype to promote survival. In this
      review, we discuss the pathophysiology of AF, summarize studies supporting a
      common remodeling program in AF and hibernating myocardium, and propose future
      therapeutic implications of this emerging paradigm. Ultimately, better
      understanding of the molecular mechanisms of atrial myocyte remodeling during the
      onset of AF and the transition from paroxysmal to persistent stages of the
      disease may facilitate discovery of new therapeutic targets. 

PMID- 26221600
TI  - Runx2/miR-3960/miR-2861 Positive Feedback Loop Is Responsible for Osteogenic
      Transdifferentiation of Vascular Smooth Muscle Cells.
AB  - We previously reported that Runx2/miR-3960/miR-2861 regulatory feedback loop
      stimulates osteoblast differentiation. However, the effect of this feedback loop
      on the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs)
      remains unclear. Our recent study showed that miR-2861 and miR-3960 expression
      increases significantly during beta-glycerophosphate-induced osteogenic
      transdifferentiation of VSMCs. Overexpression of miR-2861 or miR-3960 in VSMCs
      enhances beta-glycerophosphate-induced osteoblastogenesis, whereas inhibition of
      miR-2861 or miR-3960 expression attenuates it. MiR-2861 or miR-3960 promotes
      osteogenic transdifferentiation of VSMCs by targeting histone deacetylase 5 or
      Homeobox A2, respectively, resulting in increased runt-related transcription
      factor 2 (Runx2) protein production. Furthermore, overexpression of Runx2 induces
      miR-2861 and miR-3960 transcription, and knockdown of Runx2 attenuates beta
      glycerophosphate-induced miR-2861 and miR-3960 transcription in VSMCs. Thus, our
      data show that Runx2/miR-3960/miR-2861 positive feedback loop plays an important
      role in osteogenic transdifferentiation of VSMCs and contributes to vascular
      calcification. 

PMID- 26221601
TI  - Targeting Insulin-Like Growth Factor Binding Protein-3 Signaling in Triple
      Negative Breast Cancer.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is a key regulatory
      molecule of the IGF axis and can function in a tissue-specific way as both a
      tumor suppressor and promoter. Triple-negative breast cancer (TNBC) has high
      tumor expression of IGFBP-3 associated with markers of poor prognosis and,
      although accounting for 15-20% of all breast cancers, is responsible for
      disproportionate rates of morbidity and mortality. Because they lack estrogen and
      progesterone receptors and overexpression of HER2, TNBC are resistant to
      treatments that target these molecules, making the development of new therapies
      an important goal. In addition to frequent high expression of IGFBP-3, these
      tumors also express EGFR highly, but targeting EGFR signaling alone in TNBC has
      been of little success. Identification of a functional growth-stimulatory
      interaction between EGFR and IGFBP-3 signaling prompted investigation into
      cotargeting these pathways as a novel therapy for TNBC. This involves inhibition
      of both EGFR kinase activity and a mediator of IGFBP-3's stimulatory bioactivity,
      sphingosine kinase-1 (SphK1), and has shown promise in a preclinical setting.
      Functional interaction between EGFR and IGFBP-3 may also promote chemoresistance
      in TNBC, and delineating the mechanisms involved may identify additional targets
      for development of therapies in cancers that express both IGFBP-3 and EGFR. 

PMID- 26221602
TI  - Molecular Pathogenesis of Anti-NMDAR Encephalitis.
AB  - Anti-NMDAR encephalitis is a recently identified autoimmune disease, described by
      an immune-mediated loss of NMDA glutamate receptors, resulting in progressive
      mental deterioration. To date, literature on anti-NMDAR encephalitis has been
      largely clinically oriented, including descriptions of the clinical presentation
      and course, diagnostic methods, and potential clinical treatments. However, the
      underlying molecular mechanisms contributing to the complex immunological
      cellular transformation that is associated with the progression of anti-NMDAR
      encephalitis remain to be adequately explored. This review will provide a summary
      of the current literature on anti-NMDAR encephalitis, including the immunologic
      molecular mechanisms contributing to disease progression. In particular this
      review will focus on the effect of anti-NMDAR on GluN2-NMDAR expression and the
      molecular transformation of B and T leukocytes in the loss of self-tolerance.
      Further research on the immunologic mechanisms contributing to anti-NMDAR
      encephalitis may provide an avenue for future novel diagnostic approaches, such
      as immunologic surveillance, as well as new therapeutic strategies for this
      recently identified autoimmune disease. 

PMID- 26221603
TI  - Semiautomatic, Quantitative Measurement of Aortic Valve Area Using CTA:
      Validation and Comparison with Transthoracic Echocardiography.
AB  - OBJECTIVE: The aim of this work was to develop a fast and robust (semi)automatic
      segmentation technique of the aortic valve area (AVA) MDCT datasets. METHODS: The
      algorithm starts with detection and cropping of Sinus of Valsalva on MPR image.
      The cropped image is then binarized and seed points are manually selected to
      create an initial contour. The contour moves automatically towards the edge of
      aortic AVA to obtain a segmentation of the AVA. AVA was segmented
      semiautomatically and manually by two observers in multiphase cardiac CT scans of
      25 patients. Validation of the algorithm was obtained by comparing to
      Transthoracic Echocardiography (TTE). Intra- and interobserver variability were
      calculated by relative differences. Differences between TTE and MDCT manual and
      semiautomatic measurements were assessed by Bland-Altman analysis. Time required
      for manual and semiautomatic segmentations was recorded. RESULTS: Mean
      differences from TTE were -0.19 (95% CI: -0.74 to 0.34) cm(2) for manual and 
      0.10 (95% CI: -0.45 to 0.25) cm(2) for semiautomatic measurements. Intra- and
      interobserver variability were 8.4 +/- 7.1% and 27.6 +/- 16.0% for manual, and
      5.8 +/- 4.5% and 16.8 +/- 12.7% for semiautomatic measurements, respectively.
      CONCLUSION: Newly developed semiautomatic segmentation provides an accurate, more
      reproducible, and faster AVA segmentation result.

PMID- 26221605
TI  - Fixation of Light Weight Polypropylene Mesh with n-Butyl-2-cyanocrylate in Pelvic
      Floor Surgery: Experimental Design Approach in Sheep for Effectiveness
      Evaluation.
AB  - OBJECTIVE: The aim of this study was to find a proper experimental design and to
      evaluate n-butyl-2-cyanoacrylate (Histoacryl) as a fixation method for a light
      weight and large pore PP mesh (Synthetic PP Mesh-1) using the sheep as an animal
      model. METHODS: Posterior vaginal implantation by means of episiotomy was used to
      implant 8 ewes which were evaluated macroscopically and histologically at 3
      months (n = 4) and 6 months (n = 4) post-surgery. In previous pilot studies
      anterior vaginal implantation was evaluated, as well as different synthetic mesh
      materials, sizes and fixation methods (n = 1 to 3) during three weeks. In all
      cases a clinical evaluation of the animal was performed. RESULTS: A reduction in
      the mesh size (Synthetic PP Mesh-1) together with precise application of the
      surgical glue Histoacryl to fix the mesh yielded significantly better
      histocompatibility results (P < 0.01) compared to larger size or other fixation
      methods. CONCLUSION: The combination of Synthetic PP Mesh-1 with Histoacryl
      offered a high degree of graft integration without vaginal ulceration and a
      minimal foreign body reaction, being the sheep a proper animal model to test
      these types of medical devices.

PMID- 26221604
TI  - MicroRNA Clusters in the Adult Mouse Heart: Age-Associated Changes.
AB  - The microRNAs and microRNA clusters have been implicated in normal cardiac
      development and also disease, including cardiac hypertrophy, cardiomyopathy,
      heart failure, and arrhythmias. Since a microRNA cluster has from two to dozens
      of microRNAs, the expression of a microRNA cluster could have a substantial
      impact on its target genes. In the present study, the configuration and
      distribution of microRNA clusters in the mouse genome were examined at various
      inter-microRNA distances. Three important microRNA clusters that are
      significantly impacted during adult cardiac aging, the miR-17-92, miR-106a-363,
      and miR-106b-25, were also examined in terms of their genomic location, RNA
      transcript character, sequence homology, and their relationship with the
      corresponding microRNA families. Multiple microRNAs derived from the three
      clusters potentially target various protein components of the cdc42-SRF signaling
      pathway, which regulates cytoskeleton dynamics associated with cardiac structure
      and function. The data indicate that aging impacted the expression of both guide
      and passenger strands of the microRNA clusters; nutrient stress also affected the
      expression of the three microRNA clusters. The miR-17-92, miR-106a-363, and miR
      106b-25 clusters are likely to impact the Cdc42-SRF signaling pathway and thereby
      affect cardiac morphology and function during pathological conditions and the
      aging process. 

PMID- 26221606
TI  - Retinal Imaging of Infants on Spectral Domain Optical Coherence Tomography.
AB  - Spectral domain coherence tomography (SD OCT) has become an important tool in the
      management of pediatric retinal diseases. It is a noncontact imaging device that
      provides detailed assessment of the microanatomy and pathology of the infant
      retina with a short acquisition time allowing office examination without the
      requirement of anesthesia. Our understanding of the development and maturation of
      the infant fovea has been enhanced by SD OCT allowing an in vivo assessment that
      correlates with histopathology. This has helped us understand the critical
      correlation of foveal development with visual potential in the first year of life
      and beyond. In this review, we summarize the recent literature on the clinical
      applications of SD OCT in studying the pathoanatomy of the infant macula, its
      ability to detect subclinical features, and its correlation with disease and
      vision. Retinopathy of prematurity and macular edema have been discussed in
      detail. The review also summarizes the current status of SD OCT in other infant
      retinal conditions, imaging the optic nerve, the choroid, and the retinal nerve
      fibre in infants and children, and suggests future areas of research. 

PMID- 26221608
TI  - Toxicity of Graphene Shells, Graphene Oxide, and Graphene Oxide Paper Evaluated
      with Escherichia coli Biotests.
AB  - The plate-like graphene shells (GS) produced by an original methane pyrolysis
      method and their derivatives graphene oxide (GO) and graphene oxide paper (GO-P)
      were evaluated with luminescent Escherichia coli biotests and additional
      bacterial-based assays which together revealed the graphene-family nanomaterials'
      toxicity and bioactivity mechanisms. Bioluminescence inhibition assay,
      fluorescent two-component staining to evaluate cell membrane permeability, and
      atomic force microscopy data showed GO expressed bioactivity in aqueous
      suspension, whereas GS suspensions and the GO-P surface were assessed as nontoxic
      materials. The mechanism of toxicity of GO was shown not to be associated with
      oxidative stress in the targeted soxS::lux and katG::lux reporter cells; also, GO
      did not lead to significant mechanical disruption of treated bacteria with the
      release of intracellular DNA contents into the environment. The well-coordinated
      time- and dose-dependent surface charge neutralization and transport and
      energetic disorders in the Escherichia coli cells suggest direct membrane
      interaction, internalization, and perturbation (i.e., "membrane stress") as a
      clue to graphene oxide's mechanism of toxicity. 

PMID- 26221607
TI  - MicroRNAs: Novel Players in Aortic Aneurysm.
AB  - An aortic aneurysm (AA) is a common disease with potentially life-threatening
      complications. Despite significant improvements in the diagnosis and treatment of
      AA, the associated morbidity and mortality remain high. MicroRNAs (miRNAs, miR)
      are small noncoding ribonucleic acids that negatively regulate gene expression at
      the posttranscriptional level by inhibiting mRNA translation or promoting mRNA
      degradation. miRNAs are recently reported to be critical modulators for vascular
      cell functions such as cell migration, contraction, differentiation,
      proliferation, and apoptosis. Increasing evidences suggest crucial roles of
      miRNAs in the pathogenesis and progression of cardiovascular diseases such as
      coronary artery disease, heart failure, arterial hypertension, and cardiac
      arrhythmias. Recently, some miRNAs, such as miR-24, miR-155, miR-205, miR-712,
      miR-21, miR-26a, miR-143/145, miR-29, and miR-195, have been demonstrated to be
      differentially expressed in the diseased aortic tissues and strongly associated
      with the development of AA. In the present paper, we reviewed the recent
      available literature regarding the role of miRNAs in the pathogenesis of AA.
      Moreover, we discuss the potential use of miRNAs as diagnostic and prognostic
      biomarkers and novel targets for development of effective therapeutic strategies
      for AA. 

PMID- 26221609
TI  - A Novel Mutation of SMAD3 Identified in a Chinese Family with Aneurysms
      Osteoarthritis Syndrome.
AB  - Aneurysms-osteoarthritis syndrome (AOS) is a recently delineated autosomal
      dominant disorder characterized by aneurysms, dissections, and tortuosity
      throughout the arterial tree in association with early onset osteoarthritis, mild
      craniofacial features, and skeletal and cutaneous anomalies. Previous studies
      have demonstrated that mutations in SMAD3, a key regulator of TGF-beta signal
      transduction, contribute to AOS. Here, we investigated a family of three
      generations affected by AOS. A novel SMAD3 mutation, c.266G>A (p.C89Y), was
      identified and cosegregated with the affected individuals in this family. Our
      finding expands the mutation spectrum of SMAD3 gene and further strengthens the
      connection between the presence of aneurysms-osteoarthritis phenotype and SMAD3
      mutations, which facilitates the understanding of the genotype-phenotype
      correlation of AOS. 

PMID- 26221611
TI  - Effects of High Glucose Levels and Glycated Serum on GIP Responsiveness in the
      Pancreatic Beta Cell Line HIT-T15.
AB  - Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone produced in
      the gastrointestinal tract that stimulates glucose dependent insulin secretion.
      Impaired incretin response has been documented in diabetic patients and was
      mainly related to the inability of the pancreatic beta cells to secrete insulin
      in response to GIP. Advanced Glycation End Products (AGEs) have been shown to
      play an important role in pancreatic beta cell dysfunction. The aim of this study
      is to investigate whether the exposure to AGEs can induce GIP resistance in the
      pancreatic beta cell line HIT-T15. Cells were cultured for 5 days in low (CTR) or
      high glucose (HG) concentration in the presence of AGEs (GS) to evaluate the
      expression of GIP receptor (GIPR), the intracellular signaling activated by GIP,
      and secretion of insulin in response to GIP. The results showed that incubation
      with GS alone altered intracellular GIP signaling and decreased insulin secretion
      as compared to CTR. GS in combination with HG reduced the expression of GIPR and
      PI3K and abrogated GIP-induced AKT phosphorylation and GIP-stimulated insulin
      secretion. In conclusion, we showed that treatment with GS is associated with the
      loss of the insulinotropic effect of GIP in hyperglycemic conditions. 

PMID- 26221610
TI  - The Emerging Role of miR-223 in Platelet Reactivity: Implications in Antiplatelet
      Therapy.
AB  - Platelets are anuclear cells and are devoid of genomic DNA, but they are capable
      of de novo protein synthesis from mRNA derived from their progenitor cells,
      megakaryocytes. There is mounting evidence that microRNA (miRNA) plays an
      important role in regulating gene expression in platelets. miR-223 is the most
      abundant miRNAs in megakaryocytes and platelets. One of the miR-223-regulated
      genes is ADP P2Y12, a key target for current antiplatelet drug therapy. Recent
      studies showed that a blunted response to P2Y12 antagonist, that is, high on
      treatment platelet reactivity (HTPR), is a strong predictor of major
      cardiovascular events (MACEs) in coronary heart disease (CHD) patients receiving
      antiplatelet treatment. Recent clinical cohort study showed that the level of
      circulating miR-223 is inversely associated with MACE in CHD patients. In
      addition, our recent data demonstrated that the level of both intraplatelet and
      circulating miR-223 is an independent predictor for HTPR, thus providing a link
      between miR-223 and MACE. These lines of evidence indicate that miR-223 may serve
      as a potential regulatory target for HTPR, as well as a diagnostic tool for
      identification of HTPR in clinical settings. 

PMID- 26221612
TI  - Protective Effects of the Mushroom Lactarius deterrimus Extract on Systemic
      Oxidative Stress and Pancreatic Islets in Streptozotocin-Induced Diabetic Rats.
AB  - The aim of this study was to assess the in vivo effects of the extract of the
      medicinal mushroom, Lactarius deterrimus, when administered (60 mg/kg, i.p.)
      daily for four weeks to streptozotocin- (STZ-) induced diabetic rats. Diabetic
      rats treated with the L. deterrimus extract displayed several improved
      biochemical parameters in the circulation: reduced hyperglycemia, lower
      triglyceride concentration and reduced glycated hemoglobin, glycated serum
      protein, and advanced glycation end product (AGE) levels. This treatment also
      adjusted the diabetes-induced redox imbalance. Thus, higher activities of the
      antioxidative enzymes, superoxide dismutase, and catalase in the circulation were
      accompanied by increased levels of free intracellular thiols and glutathionylated
      proteins after treatment with the L. deterrimus extract. In addition to a
      systemic antioxidant effect, the administration of the extract to diabetic rats
      also had a positive localized effect on pancreatic islets where it decreased AGE
      formation, and increased the expression of chemokine CXCL12 protein that mediates
      the restoration of beta-cell population through the activation of the
      serine/threonine-specific Akt protein kinase prosurvival pathway. As a result,
      the numbers of proliferating cell nuclear antigen- (PCNA-) and insulin-positive
      beta-cells were increased. These results show that the ability of the L.
      deterrimus extract to alleviate oxidative stress and increase beta-cell mass
      represents a therapeutic potential for diabetes management.

PMID- 26221613
TI  - Combined Methods for Diabetic Retinopathy Screening, Using Retina Photographs and
      Tear Fluid Proteomics Biomarkers.
AB  - Background. It is estimated that 347 million people suffer from diabetes mellitus
      (DM), and almost 5 million are blind due to diabetic retinopathy (DR). The
      progression of DR can be slowed down with early diagnosis and treatment.
      Therefore our aim was to develop a novel automated method for DR screening.
      Methods. 52 patients with diabetes mellitus were enrolled into the project. Of
      all patients, 39 had signs of DR. Digital retina images and tear fluid samples
      were taken from each eye. The results from the tear fluid proteomics analysis and
      from digital microaneurysm (MA) detection on fundus images were used as the input
      of a machine learning system. Results. MA detection method alone resulted in 0.84
      sensitivity and 0.81 specificity. Using the proteomics data for analysis 0.87
      sensitivity and 0.68 specificity values were achieved. The combined data analysis
      integrated the features of the proteomics data along with the number of detected
      MAs in the associated image and achieved sensitivity/specificity values of
      0.93/0.78. Conclusions. As the two different types of data represent independent
      and complementary information on the outcome, the combined model resulted in a
      reliable screening method that is comparable to the requirements of DR screening
      programs applied in clinical routine. 

PMID- 26221614
TI  - The Effect of Autologous Platelet-Rich Gel on the Dynamic Changes of the Matrix
      Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-2 Expression in the
      Diabetic Chronic Refractory Cutaneous Ulcers.
AB  - Aim. To investigate the dynamic changes on the expression of matrix
      metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in
      the diabetic chronic refractory cutaneous ulcers after the autologous platelet
      rich gel (APG) treatment. Methods. The study was developed at the Diabetic Foot
      Care Centre, West China Hospital. The granulation tissues from the target wounds
      were taken before and within 15 days after APG application. The expression of MMP
      2 and TIMP-2 as well as transforming growth factor-beta1 (TGF-beta1) in the
      granulation tissue was detected by q TR-PCR and IHC. The relationship between the
      expression level of MMP-2 and TIMP-2 and their ratio and that of TGF-beta1 was
      analyzed. Results. The expression of MMP-2 (P < 0.05) was suppressed, and the
      expression of TIMP-2 (P < 0.05) was promoted, while the ratio of MMP-2/TIMP-2 (P
      < 0.05) was decreased after APG treatments. The expression of TGF-beta1 had
      negative correlation with the ratio of MMP-2/TIMP-2 (P < 0.05) and positive
      correlation with the expression of TIMP-2 (P < 0.05). Conclusions. APG treatment
      may suppress the expression of MMP-2, promoting that of the TIMP-2 in the
      diabetic chronic refractory cutaneous wounds. TGF-beta1 may be related to these
      effects. 

PMID- 26221615
TI  - Branched Polyethylenimine-Superparamagnetic Iron Oxide Nanoparticles (bPEI
      SPIONs) Improve the Immunogenicity of Tumor Antigens and Enhance Th1 Polarization
      of Dendritic Cells.
AB  - Nanoparticles in the field of dendritic cell (DC) research are emerging as a
      promising method of enhancing the efficacy of cancer immunotherapy. We
      investigated the effect of branched polyethylenimine-superparamagnetic iron oxide
      nanoparticles (bPEI-SPIONs) on tumor cells loaded onto DCs. The tumor antigens
      were prepared as follows: (1) apoptotic U266 cells with ultraviolet B (UVB)
      irradiation followed by a 2 h incubation in the absence (2 h postirradiated
      cells) or (2) presence of bPEI-SPIONs (bPEI-SPION 2 h postirradiated cells) and
      (3) apoptotic U266 cells with UVB irradiation followed by an overnight 16 h
      incubation (16 h postirradiated cells). bPEI-SPIONs render U266 cells sensitive
      to UVB irradiation through reactive oxygen species production to accelerate
      apoptotic death. The 2 h postirradiated cells and bPEI-SPION 2 h postirradiated
      cells released immunogenic proteins, including Hsp70, Hsp90, and HMGB1. The DCs
      loaded with bPEI-SPION 2 h postirradiated cells showed the highest IL-12p70
      production and Th1 polarization compared with other DCs. These results suggest
      that bPEI-SPIONs are a promising method of enhancing the immunogenicity of tumor
      cells and promoting Th1 polarization of DCs loaded with these tumor cells. 

PMID- 26221616
TI  - DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the
      Treatment of Advanced CIA in Mice.
AB  - We have previously demonstrated that semimature dendritic cell- (smDC-) based
      immunotherapy is effective for the treatment of collagen-induced arthritis (CIA)
      prior to disease onset. In the present study, we examined the efficacy of
      combination therapy with smDCs and methotrexate (MTX) in advanced CIA with a
      score of 2-3. Combination therapy with low-dose MTX and type II collagen- (CII-)
      pulsed smDCs (CII-smDCs) was more effective in inhibiting disease progression
      than high or low-dose MTX alone or a combination of high dose MTX and CII-smDCs.
      The effect of CII-smDCs alone was also comparable to the combination therapy.
      CD4(+)Foxp3(+) Treg populations and IL-10 secretion markedly increased, and CII
      specific autoreactive T cells decreased in mice treated with CII-smDCs alone or
      in combination with MTX. Combination therapy reduced the secretion of interferon
      gamma (IFN-gamma) and IL-17 with little influence on the IL-4 secretion in the
      mixed leukocyte reaction. These results imply that the combination therapy with
      low-dose MTX and smDCs is effective in controlling advanced CIA by enhancing Treg
      population and suppresses antigen-specific Th1/Th17 immunity, rather than
      initiating Th1 to Th2 immune deviation. Our findings provide a better
      understanding of the DC therapy in combination with MTX for the treatment of
      patients with rheumatoid arthritis (RA). 

PMID- 26221617
TI  - The Challenge of t (6;9) and FLT3-Positive Acute Myelogenous Leukemia in a Young
      Adult.
AB  - Translocation t(6;9) is a rare cytogenetic abnormality found in fewer than 5% of
      pediatric and adult cases of acute myelogenous leukemia (AML). The outcomes of
      t(6;9) AML are generally poor, with low five-year overall survival and increased
      risk for relapse. Furthermore, FLT3-ITD is one of the most common molecular
      abnormalities found in AML that is associated with increased risk of treatment
      failure and mortality. Allogeneic hematopoietic cell transplantation (HCT) with
      the best available donor is a standard treatment option for these cases once
      remission is achieved. We report a challenging case of t(6;9) and FLT3-positive
      AML in a young adult male. After failing multiple standard induction regimens,
      morphologic remission was eventually achieved with a FLT3 inhibitor (sorafenib)
      and a hypomethylating agent (azacytidine). However, despite allogeneic HCT and re
      initiation of sorafenib in the post-HCT setting, he experienced early relapse
      with the original [FLT3-ITD and t(6;9)] and new (FLT3-D835 and +8) molecular and
      cytogenetic markers, respectively. This case highlights the need for improved
      strategies in the post-HCT setting for high-risk AML.

PMID- 26221618
TI  - Blockade of non-opioid excitatory effects of spinal dynorphin A at bradykinin
      receptors.
AB  - Dynorphin A (Dyn A) is an endogenous opioid ligand that possesses neuroinhibitory
      (antinociceptive) effects via MU, delta, and kappa opioid receptors. However,
      under chronic pain conditions, up-regulated spinal Dyn A can also interact with
      bradykinin receptors (BRs) to promote hyperalgesia through a
      neuroexcitatory(pronociceptive) effect. These excitatory effects cannot be
      blocked by an opioid antagonist, and thus are non-opioid in nature. On the basis
      of the structural dissimilarity between Dyn A and endogenous BR ligands,
      bradykinin(BK) and kallidin (KD), Dyn A's interaction with BRs could not be
      predicted, and provided an opportunity to identify a novel potential
      neuroexcitatory target. Systematic structure-activity relationship (SAR) studies
      discovered a minimum pharmacophore of Dyn A, [des-Arg7]-Dyn A-(4-11) LYS1044 for
      antagonist activity at the BRs, along with insights into the key structural
      features for BRs recognition, i.e., amphipathicity. The des-Tyr fragment of
      dynorphin does not bind to opioid receptors. Intrathecal administration of des
      Tyr dynorphin produces hyperalgesia reminiscent of behaviors seen in peripheral n
      europathic pain models and at higher doses, neurotoxicity. Our lead ligand
      LYS1044 negatively modulated Dyn A-(2-13)-induced neuroexcitatory effects in
      naive animals and blocked mechanical hypersensitivity and thermal hyperalgesia in
      a dose-dependent manner in animals with experimental neuropathic pain. Based on
      these results, ligand LYS1044 might prevent abnormal pain states by blocking the
      neuroexcitatory effects of increased levels of Dyn A that are seen in
      experimental models of neuropathic pain and that likely promote excitation
      mediated by BRs in the spinal cord.

PMID- 26221619
TI  - Effects of Brief Alcohol Interventions on Drinking and Driving among Youth: A
      Systematic Review and Meta-analysis.
AB  - OBJECTIVE: Alcohol-impaired driving persists as a major cause of traffic
      fatalities and injuries among young drivers. This meta-analysis examined whether
      brief alcohol interventions were effective in reducing driving after drinking
      among adolescents and young adults. METHOD: Our systematic search identified 12
      experimental/quasi-experimental evaluations (16 intervention groups) that
      measured driving while intoxicated and related consequences and provided data for
      effect size calculation (N = 5,664; M age =17 years; 57% male). The studies were
      published between 1991 and 2011. Three-level random-effects meta-analyses using a
      structural equation modeling approach were used to summarize the effects of the
      interventions. RESULTS: Compared with controls, participants in brief alcohol
      interventions reported reduced drinking and driving and related consequences (g =
      0.15, 95% CI [0.08, 0.21]). Supplemental analyses indicated that reductions in
      driving while intoxicated were positively associated with the reduced post
      intervention heavy use of alcohol. These findings were not attenuated by study
      design or implementation factors. CONCLUSIONS: Brief alcohol interventions under
      5 hours of contact may constitute a promising preventive approach targeting
      drinking and driving among adolescents and young adults. Reducing heavy episodic
      alcohol consumption appeared to be a major factor in reducing drunk-driving
      instances. Interpretation of the findings must be made with caution, however,
      given the possibility of publication bias and the small observed effect size.
      Future research should focus on the exact mechanisms of behavior change leading
      to beneficial outcomes of brief alcohol interventions and the potential
      effectiveness of combined brief interventions and other preventive approaches.

PMID- 26221620
TI  - ECG Prediction Based on Classification via Neural Networks and Linguistic Fuzzy
      Logic Forecaster.
AB  - The paper deals with ECG prediction based on neural networks classification of
      different types of time courses of ECG signals. The main objective is to
      recognise normal cycles and arrhythmias and perform further diagnosis. We
      proposed two detection systems that have been created with usage of neural
      networks. The experimental part makes it possible to load ECG signals, preprocess
      them, and classify them into given classes. Outputs from the classifiers carry a
      predictive character. All experimental results from both of the proposed
      classifiers are mutually compared in the conclusion. We also experimented with
      the new method of time series transparent prediction based on fuzzy transform
      with linguistic IF-THEN rules. Preliminary results show interesting results based
      on the unique capability of this approach bringing natural language
      interpretation of particular prediction, that is, the properties of time series. 

PMID- 26221621
TI  - Erratum to "N-Screen Aware Multicriteria Hybrid Recommender System Using Weight
      Based Subspace Clustering".

PMID- 26221622
TI  - A Robust H infinity Controller for an UAV Flight Control System.
AB  - The objective of this paper is the implementation and validation of a robust H
      infinity controller for an UAV to track all types of manoeuvres in the presence
      of noisy environment. A robust inner-outer loop strategy is implemented. To
      design the H infinity robust controller in the inner loop, H infinity control
      methodology is used. The two controllers that conform the outer loop are designed
      using the H infinity Loop Shaping technique. The reference vector used in the
      control architecture formed by vertical velocity, true airspeed, and heading
      angle, suggests a nontraditional way to pilot the aircraft. The simulation
      results show that the proposed control scheme works well despite the presence of
      noise and uncertainties, so the control system satisfies the requirements. 

PMID- 26221623
TI  - H.264 SVC Complexity Reduction Based on Likelihood Mode Decision.
AB  - H.264 Advanced Video Coding (AVC) was prolonged to Scalable Video Coding (SVC).
      SVC executes in different electronics gadgets such as personal computer, HDTV,
      SDTV, IPTV, and full-HDTV in which user demands various scaling of the same
      content. The various scaling is resolution, frame rate, quality, heterogeneous
      networks, bandwidth, and so forth. Scaling consumes more encoding time and
      computational complexity during mode selection. In this paper, to reduce encoding
      time and computational complexity, a fast mode decision algorithm based on
      likelihood mode decision (LMD) is proposed. LMD is evaluated in both temporal and
      spatial scaling. From the results, we conclude that LMD performs well, when
      compared to the previous fast mode decision algorithms. The comparison parameters
      are time, PSNR, and bit rate. LMD achieve time saving of 66.65% with 0.05%
      detriment in PSNR and 0.17% increment in bit rate compared with the full search
      method. 

PMID- 26221624
TI  - FoodWiki: Ontology-Driven Mobile Safe Food Consumption System.
AB  - An ontology-driven safe food consumption mobile system is considered. Over 3,000
      compounds are being added to processed food, with numerous effects on the food:
      to add color, stabilize, texturize, preserve, sweeten, thicken, add flavor,
      soften, emulsify, and so forth. According to World Health Organization,
      governments have lately focused on legislation to reduce such ingredients or
      compounds in manufactured foods as they may have side effects causing health
      risks such as heart disease, cancer, diabetes, allergens, and obesity. By
      supervising what and how much to eat as well as what not to eat, we can maximize
      a patient's life quality through avoidance of unhealthy ingredients. Smart e
      health systems with powerful knowledge bases can provide suggestions of
      appropriate foods to individuals. Next-generation smart knowledgebase systems
      will not only include traditional syntactic-based search, which limits the
      utility of the search results, but will also provide semantics for rich
      searching. In this paper, performance of concept matching of food ingredients is
      semantic-based, meaning that it runs its own semantic based rule set to infer
      meaningful results through the proposed Ontology-Driven Mobile Safe Food
      Consumption System (FoodWiki). 

PMID- 26221625
TI  - A Hybrid Swarm Intelligence Algorithm for Intrusion Detection Using Significant
      Features.
AB  - Intrusion detection has become a main part of network security due to the huge
      number of attacks which affects the computers. This is due to the extensive
      growth of internet connectivity and accessibility to information systems
      worldwide. To deal with this problem, in this paper a hybrid algorithm is
      proposed to integrate Modified Artificial Bee Colony (MABC) with Enhanced
      Particle Swarm Optimization (EPSO) to predict the intrusion detection problem.
      The algorithms are combined together to find out better optimization results and
      the classification accuracies are obtained by 10-fold cross-validation method.
      The purpose of this paper is to select the most relevant features that can
      represent the pattern of the network traffic and test its effect on the success
      of the proposed hybrid classification algorithm. To investigate the performance
      of the proposed method, intrusion detection KDDCup'99 benchmark dataset from the
      UCI Machine Learning repository is used. The performance of the proposed method
      is compared with the other machine learning algorithms and found to be
      significantly different. 

PMID- 26221626
TI  - Effective Filtering of Query Results on Updated User Behavioral Profiles in Web
      Mining.
AB  - Web with tremendous volume of information retrieves result for user related
      queries. With the rapid growth of web page recommendation, results retrieved
      based on data mining techniques did not offer higher performance filtering rate
      because relationships between user profile and queries were not analyzed in an
      extensive manner. At the same time, existing user profile based prediction in web
      data mining is not exhaustive in producing personalized result rate. To improve
      the query result rate on dynamics of user behavior over time, Hamilton Filtered
      Regime Switching User Query Probability (HFRS-UQP) framework is proposed. HFRS
      UQP framework is split into two processes, where filtering and switching are
      carried out. The data mining based filtering in our research work uses the
      Hamilton Filtering framework to filter user result based on personalized
      information on automatic updated profiles through search engine. Maximized result
      is fetched, that is, filtered out with respect to user behavior profiles. The
      switching performs accurate filtering updated profiles using regime switching.
      The updating in profile change (i.e., switches) regime in HFRS-UQP framework
      identifies the second- and higher-order association of query result on the
      updated profiles. Experiment is conducted on factors such as personalized
      information search retrieval rate, filtering efficiency, and precision ratio. 

PMID- 26221627
TI  - An Optimal CDS Construction Algorithm with Activity Scheduling in Ad Hoc
      Networks.
AB  - A new energy efficient optimal Connected Dominating Set (CDS) algorithm with
      activity scheduling for mobile ad hoc networks (MANETs) is proposed. This
      algorithm achieves energy efficiency by minimizing the Broadcast Storm Problem
      [BSP] and at the same time considering the node's remaining energy. The Connected
      Dominating Set is widely used as a virtual backbone or spine in mobile ad hoc
      networks [MANETs] or Wireless Sensor Networks [WSN]. The CDS of a graph
      representing a network has a significant impact on an efficient design of routing
      protocol in wireless networks. Here the CDS is a distributed algorithm with
      activity scheduling based on unit disk graph [UDG]. The node's mobility and
      residual energy (RE) are considered as parameters in the construction of stable
      optimal energy efficient CDS. The performance is evaluated at various node
      densities, various transmission ranges, and mobility rates. The theoretical
      analysis and simulation results of this algorithm are also presented which yield
      better results. 

PMID- 26221628
TI  - Personal Authentication Using Multifeatures Multispectral Palm Print Traits.
AB  - Biometrics authentication is an effective method for automatically recognizing a
      person's identity with high confidence. Multispectral palm print biometric system
      is relatively new biometric technology and is in the progression of being
      endlessly refined and developed. Multispectral palm print biometric system is a
      promising biometric technology for use in various applications including banking
      solutions, access control, hospital, construction, and forensic applications.
      This paper proposes a multispectral palm print recognition method with extraction
      of multiple features using kernel principal component analysis and modified
      finite radon transform. Finally, the images are classified using Local Mean K
      Nearest Centroid Neighbor algorithm. The proposed method efficiently accommodates
      the rotational, potential deformations and translational changes by encoding the
      orientation conserving features. The proposed system analyses the hand vascular
      authentication using two databases acquired with touch-based and contactless
      imaging setup collected from multispectral Poly U palm print database and CASIA
      database. The experimental results clearly demonstrate that the proposed
      multispectral palm print authentication obtained better result compared to other
      methods discussed in the literature. 

PMID- 26221630
TI  - Recent progress in the fundamental understanding of hydrophilic interaction
      chromatography (HILIC).
AB  - With the exponential growth in the application of the HILIC technique, there has
      been a significant progress in understanding the fundamental aspects of
      hydrophilic interaction chromatography. The experimental studies tend to be more
      extensive in terms of the number of stationary phases investigated and the number
      of probe compounds employed in comparison with the earlier studies; and more
      theoretical studies in quantitative structure retention relationship (QSRR) and
      molecular dynamics simulations have also been published and provide molecular
      level insights into the retention mechanism. This review focuses on the recent
      progress in understanding the retention mechanism, retention models, selectivity,
      and the kinetic performance of HILIC. A better understanding of these fundamental
      aspects will undoubtedly facilitate more applications of this chromatographic
      technique in a wider range of fields. 

PMID- 26221629
TI  - Use of Probiotics to Control Aflatoxin Production in Peanut Grains.
AB  - Probiotic microorganisms (Saccharomyces cerevisiae var. boulardii, S. cerevisiae
      UFMG 905, and Lactobacillus delbrueckii UFV H2b20) were evaluated as biological
      control agents to reduce aflatoxin and spore production by Aspergillus
      parasiticus IMI 242695 in peanut. Suspensions containing the probiotics alone or
      in combinations were tested by sprinkling on the grains followed by incubation
      for seven days at 25 degrees C. All probiotic microorganisms, in live and
      inactivated forms, significantly reduced A. parasiticus sporulation, but the best
      results were obtained with live cells. The presence of probiotics also altered
      the color of A. parasiticus colonies but not the spore morphology. Reduction in
      aflatoxin production of 72.8 and 65.8% was observed for S. boulardii and S.
      cerevisiae, respectively, when inoculated alone. When inoculated in pairs, all
      probiotic combinations reduced significantly aflatoxin production, and the best
      reduction was obtained with S. boulardii plus L. delbrueckii (96.1%) followed by
      S. boulardii plus S. cerevisiae and L. delbrueckii plus S. cerevisiae (71.1 and
      66.7%, resp.). All probiotics remained viable in high numbers on the grains even
      after 300 days. The results of the present study suggest a different use of
      probiotics as an alternative treatment to prevent aflatoxin production in peanut
      grains. 

PMID- 26221631
TI  - Analysis of ATP and AMP binding to a DNA aptamer and its imidazole-tethered
      derivatives by surface plasmon resonance.
AB  - Imidazole was tethered to the C5 position of thymine in an ATP-binding DNA
      aptamer with two types of linkers, and the affinities of each aptamer for ATP and
      AMP were determined by surface plasmon resonance measurements. The imidazole
      tethered aptamers exhibited higher affinity for ATP, almost independently of the
      linker structure or the modification site. 

PMID- 26221632
TI  - Novel glycopolymer hydrogels as mucosa-mimetic materials to reduce animal
      testing.
AB  - Glycopolymer hydrogels capable of mimicking mucosal tissue in mucoadhesion
      testing have been designed. Liquid formulations containing mucoadhesive polymers
      were found to be retained on these tissues to the same extent as ex vivo gastric
      mucosa, when using a dynamic method of assessing mucoadhesion. 

PMID- 26221633
TI  - Restricted diffusion of guest molecules in polymer thin films on solid substrates
      as revealed by three-dimensional single-molecule tracking.
AB  - 3D single-molecule tracking revealed that the translational diffusion of guest
      dyes in poly(2-hydroxyethyl acrylate) thin films on glass substrates was confined
      in a horizontal layer at a distance longer than 300-700 nm from the surface of
      the substrate. This peculiar long-range effect suggests that the interaction
      between the host polymer and the interface could affect the properties of
      polymers at a much longer distance than conventionally estimated. 

PMID- 26221634
TI  - A simple synthesis of nitrogen-doped carbon micro- and nanotubes.
AB  - Nitrogen-doped carbon nanotubes (N-CNTs) have shown promising performance in a
      variety of applications: catalysts, catalyst supports, lithium-ion batteries and
      supercapacitors. While chemical vapor deposition continues to be the most common
      method for N-CNT fabrication, its complexity and high cost have prevented the
      practical implementation of N-CNTs on a larger scale. Here, we describe a new and
      simple method for N-CNT synthesis. This method is not only potentially scalable
      to any required level but also allows for the control of the tube size (20-1000
      nm in diameter) and nitrogen doping levels (4-9 at%) through the selection of
      most suitable transition metal and heat-treatment conditions. 

PMID- 26221635
TI  - Self-assembled Ti3C2Tx MXene film with high gravimetric capacitance.
AB  - Binder-free MXene films comprising Ti3C2Tx nanoflakes in a face-to-face fashion,
      achieved by a simple dropping-mild baking approach, exhibit high gravimetric
      capacitances up to 499 F g(-1) with excellent cyclability and rate performances.
      The entire electrode system including Ni-foam and MXene film shows volumetric
      capacitances in the range of 84-226 F cm(-3) depending on the loadings of MXene
      as active material. 

PMID- 26221636
TI  - Low-valent iron: an Fe(I) ate compound as a building block for a linear
      trinuclear Fe cluster.
AB  - A low-valent trinuclear iron complex with an unusual linear Fe(I)-Fe(II)-Fe(I)
      unit is presented. It is accessed in a rational approach using a salt metathesis
      reaction between a new anionic Fe(I) containing heterocycle and FeCl2. Its
      electronic structure was studied by single crystal XRD analysis, EPR and
      Mossbauer spectroscopy, and magnetic susceptibility measurements.

PMID- 26221637
TI  - A two-step fluorinase enzyme mediated (18)F labelling of an RGD peptide for
      positron emission tomography.
AB  - A two-step radiolabelling protocol of a cancer relevant cRGD peptide is described
      where the fluorinase enzyme is used to catalyse a transhalogenation reaction to
      generate [(18)F]-5'-fluoro-5'-deoxy-2-ethynyladenosine, [(18)F]FDEA, followed by
      a 'click' reaction to an azide tethered cRGD peptide. This protocol offers
      efficient radiolabelling of a biologically relevant peptide construct in water at
      pH 7.8, 37  degrees C in 2 hours, which was metabolically stable in rats and
      retained high affinity for alphaVbeta3 integrin. 

PMID- 26221638
TI  - Highly transparent and flexible polyimide/ZrO2 nanocomposite optical films with a
      tunable refractive index and Abbe number.
AB  - In this study, novel thermally stable zirconia-containing polyimides (PI/ZrO2)
      with excellent optical properties have been prepared successfully. The obtained
      flexible PI/ZrO2 hybrid films revealed excellent optical transparency, a tunable
      refractive index and an Abbe number up to 1.804 and 32.18, respectively, which
      are crucial for optical devices. In addition, the PI/ZrO2 hybrid films also
      exhibit a higher Abbe number and transparency in the visible light region due to
      a larger energy band gap of ZrO2 than the corresponding PI/TiO2 system. 

PMID- 26221639
TI  - Photophysical efficiency-boost of aqueous aluminium phthalocyanine by hybrid
      formation with nano-clays.
AB  - Novel organic-inorganic hybrid materials comprising nanoscaled layered silicates
      and native aluminium hydroxide phthalocyanine (Al(OH)Pc) allowed for the first
      time the exploitation of their unique photophysical properties in aqueous
      ambience. In particular, we were able to observe the efficient emission of
      Al(OH)Pc-nanoclay hybrids and generation of singlet oxygen in aqueous solution. 

PMID- 26221640
TI  - Antibody Standardization to Benefit  Biomedical Research.

PMID- 26221641
TI  - [Pediatric musculoskeletal disorders: Inclusion of   Manual Therapy].

PMID- 26221642
TI  - [Congenital insensitivity to pain with anhidrosis in   the literature].

PMID- 26221643
TI  - In Memoriam: Nick Myant (1917-2015).

PMID- 26221644
TI  - [From pediatrics to psychoanalysis and viceversa].

PMID- 26221645
TI  - [In Process Citation].

PMID- 26221646
TI  - [Memory protection with conformal avoidance of the hippocampal neural stem-cell
      compartment during whole-brain radiotherapy for brain metastases?].

PMID- 26221647
TI  - [Radiotherapy also for good-risk ductal carcinoma in situ? Results from a
      prospective randomized RTOG trial].

PMID- 26221648
TI  - [Prognostic benefit of postoperative radiotherapy with adjuvant chemotherapy for
      stage IIIA/N2, pathologic non-small-cell lung cancer].

PMID- 26221649
TI  - Rectus sheath hematoma in a single secondary care institution: a retrospective
      study.
AB  - PURPOSE: Rectus sheath hematoma (RSH) represents an unusual abdominal wall
      pathology, frequently confounded as acute abdomen, with high mortality rates
      reported especially among elderly patients. The purpose of this retrospective
      study was to delineate characteristics of the patients diagnosed with RSH at the
      First Surgery Department of the Saint George General Hospital of Chania, Greece
      over a 5-year period. METHODS: Seven patients with a median age of 62 years
      (range 51-85) were included in the study. Clinical features, demographics,
      management and outcome are summarized. RESULTS: The most common predisposing risk
      factor was anticoagulation. Acute onset abdominal pain and painful palpable
      abdominal mass, located more often on the right lower abdominal quadrant, were
      the most frequent initial symptoms. Management was mostly conservative [6 (85.7
      %)] with disruption of anticoagulation, analgesia and bed rest. Blood transfusion
      was performed in hemodynamic compromised patients [2 (28.5 %)]. One patient was
      not appropriately diagnosed. On admission, the patient presented severe
      hemodynamic compromise and for this reason underwent emergency explorative
      laparotomy. The majority of the patients [6 (85.7 %)] experienced an
      uncomplicated clinical recovery and were discharged home after a mean hospital
      stay of 10 days (range 7-12). CONCLUSIONS: Surgeons as well as primary care
      physicians have to be aware of the clinical diagnostic tests and include the
      condition in the differential diagnosis of acute onset abdominal pain. Prompt
      recognition will prevent unnecessary surgical intervention and potential
      complications.

PMID- 26221651
TI  - Windows into the ivory tower.

PMID- 26221650
TI  - Combined effects of aging and inflammation on renin-angiotensin  system mediate
      mitochondrial dysfunction and phenotypic  changes in cardiomyopathies.
AB  - Although the effects of aging and inflammation on the health of the cardiac
      muscle are well documented, the combined effects of aging and chronic
      inflammation on cardiac muscle are largely unknown. The renin-angiotensin system
      (RAS) has been linked independently to both aging and inflammation, but is
      understudied in the context of their collective effect. Thus, we investigated
      localized cardiac angiotensin II type I and type II receptors (AT(1)R, AT(2)R),
      downstream effectors, and phenotypic outcomes using mouse models of the
      combination of aging and inflammation and compared it to a model of aging and a
      model of inflammation. We show molecular distinction in the combined effect of
      aging and inflammation as compared to each independently. The combination
      maintained an increased AT(1)R:AT(2)R and expression of Nox2 and exhibited the
      lowest activity of antioxidants. Despite signaling pathway differences, the
      combined effect shared phenotypic similarities with aging including oxidative
      damage, fibrosis, and hypertrophy. These phenotypic similarities have dubbed
      inflammatory conditions as premature aging, but they are, in fact, molecularly
      distinct. Moreover, treatment with an AT(1)R blocker, losartan, selectively
      reversed the signaling changes and ameliorated adverse phenotypic effects in the
      combination of aging and inflammation as well as each independently.

PMID- 26221652
TI  - Sampling distributions  and the bootstrap.

PMID- 26221653
TI  - Synapses seen at different scales.

PMID- 26221654
TI  - A small molecule improves Cas9  specificity.

PMID- 26221655
TI  - Highly multiplexed transcriptome imaging.

PMID- 26221656
TI  - Splice and sequence.

PMID- 26221657
TI  - Tinkering with chromatin.

PMID- 26221658
TI  - From form to function.

PMID- 26221659
TI  - Little D, Nee R, Abbott K, et al. Cost utility analysis of sodium polystyrene
      sulfate vs. potential alternatives for chronic hyperkalemia. Clinical Nephrology,
      2014; 81: 259-268.

PMID- 26221660
TI  - Reply to the letter.

PMID- 26221661
TI  - [Effects of Training Students through a Program Simulating Medication
      Administration and Patient Instructions in Pre-training for Practical Training].
AB  - Pharmacy school students were trained in a program simulating medication
      administration and giving adherence instructions. Following the training, the
      educational effects were evaluated. Students were separated into two groups. One
      group of students played the role of pharmacists and instructed simulated
      patients on medication adherence. Another group of students played the role of
      patients receiving simulated drug therapy; they were instructed on medication
      adherence by the students playing the role of pharmacists. The educational
      effects were evaluated using a questionnaire. The scores for "recognition of
      factors that influence medication adherence" tended to increase after the
      simulation, and they increased significantly after practical training. The scores
      for "self-evaluation of technique for instructing patients on medication
      adherence" increased significantly after the simulation, and they increased even
      more after practical training. The students' understanding of the effects on
      patients who were being instructed also increased significantly after the
      simulation, and these changes were maintained after practical training. In
      particular, students became more aware of the influence of pharmacists'
      attitudes. In practical training, the simulation training was helpful for bedside
      practice at hospital pharmacies and over-the-counter service at community
      pharmacies. Thus, the use of role play and simulated patients was an effective
      method for training pharmacy students to instruct patients on medication
      adherence.

PMID- 26221662
TI  - Preface. 24th International Conference, IPMI 2015, Sabhal Mor Ostaig, Isle of
      Skye, UK, June 28 - July 3, 2015. Proceedings..

PMID- 26221663
TI  - Colocalization Estimation Using Graphical Modeling and Variational Bayesian
      Expectation Maximization: Towards a Parameter-Free Approach.
AB  - In microscopy imaging, colocalization between two biological entities (e.g.,
      protein-protein or protein-cell) refers to the (stochastic) dependencies between
      the spatial locations of the two entities in the biological specimen. Measuring
      colocalization between two entities relies on fluorescence imaging of the
      specimen using two fluorescent chemicals, each of which indicates the
      presence/absence of one of the entities at any pixel location. State-of-the-art
      methods for estimating colocalization rely on post-processing image data using an
      adhoc sequence of algorithms with many free parameters that are tuned visually.
      This leads to loss of reproducibility of the results. This paper proposes a brand
      new framework for estimating the nature and strength of colocalization directly
      from corrupted image data by solving a single unified optimization problem that
      automatically deals with noise, object labeling, and parameter tuning. The
      proposed framework relies on probabilistic graphical image modeling and a novel
      inference scheme using variational Bayesian expectation maximization for
      estimating all model parameters, including colocalization, from data. Results on
      simulated and real-world data demonstrate improved performance over the state of
      the art.

PMID- 26221664
TI  - Template-Based Multimodal Joint Generative Model of Brain Data.
AB  - The advent of large of multi-modal imaging databases opens up the opportunity to
      learn how local intensity patterns covariate between multiple modalities. These
      models can then be used to describe expected intensities in an unseen image
      modalities given one or multiple observations, or to detect deviations (e.g.
      pathology) from the expected intensity patterns. In this work, we propose a
      template-based multi-modal generative mixture-model of imaging data and apply it
      to the problems of inlier/outlier pattern classification and image synthesis.
      Results on synthetic and patient data demonstrate that the proposed method is
      able to synthesise unseen data and accurately localise pathological regions, even
      in the presence of large abnormalities. It also demonstrates that the proposed
      model can provide accurate and uncertainty-aware intensity estimates of expected
      imaging patterns.

PMID- 26221666
TI  - A Joint Acquisition-Estimation Framework for MR Phase Imaging.
AB  - Measuring the phase of the MR signal is faced with fundamental challenges such as
      phase aliasing, noise and unknown offsets of the coil array. There is a paucity
      of acquisition, reconstruction and estimation methods that rigorously address
      these challenges. This reduces the reliability of information processing in phase
      domain. We propose a joint acquisition-processing framework that addresses the
      challenges of MR phase imaging using a rigorous theoretical treatment. Our
      proposed solution acquires the multi-coil complex data without any increase in
      acquisition time. Our corresponding estimation algorithm is applied optimally
      voxel-per-voxel. Results show that our framework achieves performance gains up to
      an order of magnitude compared to existing methods.

PMID- 26221665
TI  - Generative Method to Discover Genetically Driven Image Biomarkers.
AB  - We present a generative probabilistic approach to discovery of disease subtypes
      determined by the genetic variants. In many diseases, multiple types of pathology
      may present simultaneously in a patient, making quantification of the disease
      challenging. Our method seeks common co-occurring image and genetic patterns in a
      population as a way to model these two different data types jointly. We assume
      that each patient is a mixture of multiple disease subtypes and use the joint
      generative model of image and genetic markers to identify disease subtypes guided
      by known genetic influences. Our model is based on a variant of the so-called
      topic models that uncover the latent structure in a collection of data. We derive
      an efficient variational inference algorithm to extract patterns of co-occurrence
      and to quantify the presence of heterogeneous disease processes in each patient.
      We evaluate the method on simulated data and illustrate its use in the context of
      Chronic Obstructive Pulmonary Disease (COPD) to characterize the relationship
      between image and genetic signatures of COPD subtypes in a large patient cohort.

PMID- 26221667
TI  - A Compressed-Sensing Approach for Super-Resolution Reconstruction of Diffusion
      MRI.
AB  - We present an innovative framework for reconstructing high-spatial-resolution
      diffusion magnetic resonance imaging (dMRI) from multiple low-resolution (LR)
      images. Our approach combines the twin concepts of compressed sensing (CS) and
      classical super-resolution to reduce acquisition time while increasing spatial
      resolution. We use subpixel-shifted LR images with down-sampled and non
      overlapping diffusion directions to reduce acquisition time. The diffusion signal
      in the high resolution (HR) image is represented in a sparsifying basis of
      spherical ridgelets to model complex fiber orientations with reduced number of
      measurements. The HR image is obtained as the solution of a convex optimization
      problem which can be solved using the proposed algorithm based on the alternating
      direction method of multipliers (ADMM). We qualitatively and quantitatively
      evaluate the performance of our method on two sets of in-vivo human brain data
      and show its effectiveness in accurately recovering very high resolution
      diffusion images.

PMID- 26221668
TI  - Joint Spectral Decomposition for the Parcellation of the Human Cerebral Cortex
      Using Resting-State fMRI.
AB  - Identification of functional connections within the human brain has gained a lot
      of attention due to its potential to reveal neural mechanisms. In a whole-brain
      connectivity analysis, a critical stage is the computation of a set of network
      nodes that can effectively represent cortical regions. To address this problem,
      we present a robust cerebral cortex parcellation method based on spectral graph
      theory and resting-state fMRI correlations that generates reliable parcellations
      at the single-subject level and across multiple subjects. Our method models the
      cortical surface in each hemisphere as a mesh graph represented in the spectral
      domain with its eigenvectors. We connect cortices of different subjects with each
      other based on the similarity of their connectivity profiles and construct a
      multi-layer graph, which effectively captures the fundamental properties of the
      whole group as well as preserves individual subject characteristics. Spectral
      decomposition of this joint graph is used to cluster each cortical vertex into a
      subregion in order to obtain whole-brain parcellations. Using rs-fMRI data
      collected from 40 healthy subjects, we show that our proposed algorithm computes
      highly reproducible parcellations across different groups of subjects and at
      varying levels of detail with an average Dice score of 0.78, achieving up to 9%
      better reproducibility compared to existing approaches. We also report that our
      group-wise parcellations are functionally more consistent, thus, can be reliably
      used to represent the population in network analyses.

PMID- 26221669
TI  - Joint Clustering and Component Analysis of Correspondenceless Point Sets:
      Application to Cardiac Statistical Modeling.
AB  - Construction of Statistical Shape Models (SSMs) from arbitrary point sets is a
      challenging problem due to significant shape variation and lack of explicit point
      correspondence across the training data set. In medical imaging, point sets can
      generally represent different shape classes that span healthy and pathological
      exemplars. In such cases, the constructed SSM may not generalize well, largely
      because the probability density function (pdf) of the point sets deviates from
      the underlying assumption of Gaussian statistics. To this end, we propose a
      generative model for unsupervised learning of the pdf of point sets as a mixture
      of distinctive classes. A Variational Bayesian (VB) method is proposed for making
      joint inferences on the labels of point sets, and the principal modes of
      variations in each cluster. The method provides a flexible framework to handle
      point sets with no explicit point-to-point correspondences. We also show that by
      maximizing the marginalized likelihood of the model, the optimal number of
      clusters of point sets can be determined. We illustrate this work in the context
      of understanding the anatomical phenotype of the left and right ventricles in
      heart. To this end, we use a database containing hearts of healthy subjects,
      patients with Pulmonary Hypertension (PH), and patients with Hypertrophic
      Cardiomyopathy (HCM). We demonstrate that our method can outperform traditional
      PCA in both generalization and specificity measures.

PMID- 26221670
TI  - Bootstrapped Permutation Test for Multiresponse Inference on Brain Behavior
      Associations.
AB  - Despite that diagnosis of neurological disorders commonly involves a collection
      of behavioral assessments, most neuroimaging studies investigating the
      associations between brain and behavior largely analyze each behavioral measure
      in isolation. To jointly model multiple behavioral scores, sparse multiresponse
      regression (SMR) is often used. However, directly applying SMR without
      statistically controlling for false positives could result in many spurious
      findings. For models, such as SMR, where the distribution of the model parameters
      is unknown, permutation test and stability selection are typically used to
      control for false positives. In this paper, we present another technique for
      inferring statistically significant features from models with unknown parameter
      distribution. We refer to this technique as bootstrapped permutation test (BPT),
      which uses Studentized statistics to exploit the intuition that the variability
      in parameter estimates associated with relevant features would likely be higher
      with responses permuted. On synthetic data, we show that BPT provides higher
      sensitivity in identifying relevant features from the SMR model than permutation
      test and stability selection, while retaining strong control on the false
      positive rate. We further apply BPT to study the associations between brain
      connectivity estimated from pseudo-rest fMRI data of 1139 fourteen year olds and
      behavioral measures related to ADHD. Significant connections are found between
      brain networks known to be implicated in the behavioral tasks involved. Moreover,
      we validate the identified connections by fitting a regression model on pseudo
      rest data with only those connections and applying this model on resting state
      fMRI data of 337 left out subjects to predict their behavioral scores. The
      predicted scores significantly correlate with the actual scores, hence verifying
      the behavioral relevance of the found connections.

PMID- 26221671
TI  - Group Testing for Longitudinal Data.
AB  - We consider how to test for group differences of shapes given longitudinal data.
      In particular, we are interested in differences of longitudinal models of each
      group's subjects. We introduce a generalization of principal geodesic analysis to
      the tangent bundle of a shape space. This allows the estimation of the variance
      and principal directions of the distribution of trajectories that summarize shape
      variations within the longitudinal data. Each trajectory is parameterized as a
      point in the tangent bundle. To study statistical differences in two
      distributions of trajectories, we generalize the Bhattacharyya distance in
      Euclidean space to the tangent bundle. This not only allows to take second-order
      statistics into account, but also serves as our test-statistic during permutation
      testing. Our method is validated on both synthetic and real data, and the
      experimental results indicate improved statistical power in identifying group
      differences. In fact, our study sheds new light on group differences in
      longitudinal corpus callosum shapes of subjects with dementia versus normal
      controls.

PMID- 26221672
TI  - Spatio-Temporal Signatures to Predict Retinal Disease Recurrence.
AB  - We propose a method to predict treatment response patterns based on spatio
      temporal disease signatures extracted from longitudinal spectral domain optical
      coherence tomography (SD-OCT) images. We extract spatio-temporal disease
      signatures describing the underlying retinal structure and pathology by
      transforming total retinal thickness maps into a joint reference coordinate
      system. We formulate the prediction as a multi-variate sparse generalized linear
      model regression based on the aligned signatures. The algorithm predicts if and
      when recurrence of the disease will occur in the future. Experiments demonstrate
      that the model identifies predictive and interpretable features in the spatio
      temporal signature. In initial experiments recurrence vs. non-recurrence is
      predicted with a ROC AuC of 0.99. Based on observed longitudinal morphology
      changes and a time-to-event based Cox regression model we predict the time to
      recurrence with a mean absolute error (MAE) of 1.25 months comparing favorably to
      elastic net regression (1.34 months), demonstrating the benefit of a spatio
      temporal survival model.

PMID- 26221673
TI  - A Unifying Framework for Spatial and Temporal Diffusion in Diffusion MRI.
AB  - We propose a novel framework to simultaneously represent the diffusion-weighted
      MRI (dMRI) signal over diffusion times, gradient strengths and gradient
      directions. Current frameworks such as the 3D Simple Harmonic Oscillator
      Reconstruction and Estimation basis (3D-SHORE) only represent the signal over the
      spatial domain, leaving the temporal dependency as a fixed parameter. However,
      microstructure-focused techniques such as Axcaliber and ActiveAx provide evidence
      of the importance of sampling the dMRI space over .diffusion time. Up to now
      there exists no generalized framework that simultaneously models the dependence
      of the dMRI signal in space and time. We use a functional basis to fit the 3D+t
      spatio-temporal dMRI signal, similarly to the 3D-SHORE basis in three dimensional
      'q-space'. The lowest order term in this expansion contains an isotropic
      diffusion tensor that characterizes the Gaussian displacement distribution,
      multiplied by a negative exponential. We regularize the signal fitting by
      minimizing the norm of the analytic Laplacian of the basis, and validate our
      technique on synthetic data generated using the theoretical model proposed by
      Callaghan et al. We show that our method is robust to noise, and can accurately
      describe the restricted spatio-temporal signal decay originating from tissue
      models such as cylindrical pores. From the fitting we can then estimate the axon
      radius distribution parameters along any direction using approaches similar to
      AxCaliber. We also apply our method on real data from an ActiveAx acquisition.
      Overall, our approach allows one to represent the complete 3D+t dMRI signal,
      which should prove helpful in understanding normal and pathologic nervous tissue.

PMID- 26221674
TI  - Anisotropic Distributions on Manifolds: Template Estimation and Most Probable
      Paths.
AB  - We use anisotropic diffusion processes to generalize normal distributions to
      manifolds and to construct a framework for likelihood estimation of template and
      covariance structure from manifold valued data. The procedure avoids the
      linearization that arise when first estimating a mean or template before
      performing PCA in the tangent space of the mean. We derive flow equations for the
      most probable paths reaching sampled data points, and we use the paths that are
      generally not geodesics for estimating the likelihood of the model. In contrast
      to existing template estimation approaches, accounting for anisotropy thus
      results in an algorithm that is not based on geodesic distances. To illustrate
      the effect of anisotropy and to point to further applications, we present
      experiments with anisotropic distributions on both the sphere and finite
      dimensional LDDMM manifolds arising in the landmark matching problem.

PMID- 26221675
TI  - A Riemannian Framework for Intrinsic Comparison of Closed Genus-Zero Shapes.
AB  - We present a framework for intrinsic comparison of surface metric structures and
      curvatures. This work parallels the work of Kurtek et al. on parameterization
      invariant comparison of genus zero shapes. Here, instead of comparing the
      embedding of spherically parameterized surfaces in space, we focus on the first
      fundamental form. To ensure that the distance on spherical metric tensor fields
      is invariant to parameterization, we apply the conjugation-invariant metric
      arising from the L2 norm on symmetric positive definite matrices. As a
      reparameterization changes the metric tensor by a congruent Jacobian transform,
      this metric perfectly suits our purpose. The result is an intrinsic comparison of
      shape metric structure that does not depend on the specifics of a spherical
      mapping. Further, when restricted to tensors of fixed volume form, the manifold
      of metric tensor fields and its quotient of the group of unitary diffeomorphisms
      becomes a proper metric manifold that is geodesically complete. Exploiting this
      fact, and augmenting the metric with analogous metrics on curvatures, we derive a
      complete Riemannian framework for shape comparison and reconstruction. A by
      product of our framework is a near-isometric and curvature-preserving mapping
      between surfaces. The correspondence is optimized using the fast spherical fluid
      algorithm. We validate our framework using several subcortical boundary surface
      models from the ADNI dataset.

PMID- 26221676
TI  - Multi-atlas Segmentation as a Graph Labelling Problem: Application to Partially
      Annotated Atlas Data.
AB  - Manually annotating images for multi-atlas segmentation is an expensive and often
      limiting factor in reliable automated segmentation of large databases.
      Segmentation methods requiring only a proportion of each atlas image to be
      labelled could potentially reduce the workload on expert raters tasked with
      labelling images. However, exploiting such a database of partially labelled
      atlases is not possible with state-of-the-art multi-atlas segmentation methods.
      In this paper we revisit the problem of multi-atlas segmentation and formulate
      its solution in terms of graph-labelling. Our graphical approach uses a Markov
      Random Field (MRF) formulation of the problem and constructs a graph connecting
      atlases and the target image. This provides a unifying framework for label
      propagation. More importantly, the proposed method can be used for segmentation
      using only partially labelled atlases. We furthermore provide an extension to an
      existing continuous MRF optimisation method to solve the proposed problem
      formulation. We show that the proposed method, applied to hippocampal
      segmentation of 202 subjects from the ADNI database, remains robust and accurate
      even when the proportion of manually labelled slices in the atlases is reduced to
      20%.

PMID- 26221677
TI  - Keypoint Transfer Segmentation.
AB  - We present an image segmentation method that transfers label maps of entire
      organs from the training images to the novel image to be segmented. The transfer
      is based on sparse correspondences between keypoints that represent automatically
      identified distinctive image locations. Our segmentation algorithm consists of
      three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and
      (iii) keypoint-based probabilistic transfer of organ label maps. We introduce
      generative models for the inference of keypoint labels and for image
      segmentation, where keypoint matches are treated as a latent random variable and
      are marginalized out as part of the algorithm. We report segmentation results for
      abdominal organs in whole-body CT and in contrast-enhanced CT images. The
      accuracy of our method compares favorably to common multi-atlas segmentation
      while offering a speed-up of about three orders of magnitude. Furthermore,
      keypoint transfer requires no training phase or registration to an atlas. The
      algorithm's robustness enables the segmentation of scans with highly variable
      field-of-view.

PMID- 26221678
TI  - Finite-Dimensional Lie Algebras for Fast Diffeomorphic Image Registration.
AB  - This paper presents a fast geodesic shooting algorithm for diffeomorphic image
      registration. We first introduce a novel finite-dimensional Lie algebra structure
      on the space of bandlimited velocity fields. We then show that this space can
      effectively represent initial velocities for diffeomorphic image registration at
      much lower dimensions than typically used, with little to no loss in registration
      accuracy. We then leverage the fact that the geodesic evolution equations, as
      well as the adjoint Jacobi field equations needed for gradient descent methods,
      can be computed entirely in this finite-dimensional Lie algebra. The result is a
      geodesic shooting method for large deformation metric mapping (LDDMM) that is
      dramatically faster and less memory intensive than state-of-the-art methods. We
      demonstrate the effectiveness of our model to register 3D brain images and
      compare its registration accuracy, run-time, and memory consumption with leading
      LDDMM methods. We also show how our algorithm breaks through the prohibitive time
      and memory requirements of diffeomorphic atlas building.

PMID- 26221679
TI  - Fast Optimal Transport Averaging of Neuroimaging Data.
AB  - Knowing how the Human brain is anatomically and functionally organized at the
      level of a group of healthy individuals or patients is the primary goal of
      neuroimaging research. Yet computing an average of brain imaging data defined
      over a voxel grid or a triangulation remains a challenge. Data are large, the
      geometry of the brain is complex and the between subjects variability leads to
      spatially or temporally non-overlapping effects of interest. To address the
      problem of variability, data are commonly smoothed before performing a linear
      group averaging. In this work we build on ideas originally introduced by
      Kantorovich to propose a new algorithm that can average efficiently non
      normalized data defined over arbitrary discrete domains using transportation
      metrics. We show how Kantorovich means can be linked to Wasserstein barycenters
      in order to take advantage of the entropic smoothing approach used by. It leads
      to a smooth convex optimization problem and an algorithm with strong convergence
      guarantees. We illustrate the versatility of this tool and its empirical behavior
      on functional neuroimaging data, functional MRI and magnetoencephalography (MEG)
      source estimates, defined on voxel grids and triangulations of the folded
      cortical surface.

PMID- 26221680
TI  - Joint Morphometry of Fiber Tracts and Gray Matter Structures Using Double
      Diffeomorphisms.
AB  - This work proposes an atlas construction method to jointly analyse the relative
      position and shape of fiber tracts and gray matter structures. It is based on a
      double diffeomorphism which is a composition of two diffeomorphisms. The first
      diffeomorphism acts only on the white matter keeping fixed the gray matter of the
      atlas. The resulting white matter, together with the gray matter, are then
      deformed by the second diffeomorphism. The two diffeomorphisms are related and
      jointly optimised. In this way, the, first diffeomorphisms explain the
      variability in structural connectivity within the population, namely both changes
      in the connected areas of the gray matter and in the geometry of the pathway of
      the tracts. The second diffeomorphisms put into correspondence the homologous
      anatomical structures across subjects. Fiber bundles are approximated with
      weighted prototypes using the metric of weighted currents. The atlas, the
      covariance matrix of deformation parameters and the noise variance of each
      structure are automatically estimated using a Bayesian approach. This method is
      applied to patients with Tourette syndrome and controls showing a variability in
      the structural connectivity of the left cortico-putamen circuit.

PMID- 26221681
TI  - A Robust Probabilistic Model for Motion Layer Separation in X-ray Fluoroscopy.
AB  - Fluoroscopic images are characterized by a transparent projection of 3-D
      structures from all depths to 2-D. Differently moving structures, for example due
      to breathing and heartbeat, can be described approximately using independently
      moving 2-D layers. Separating the fluoroscopic images into the motion layers is
      desirable to facilitate interpretation and diagnosis. Given the motion of each
      layer, it is state of the art to compute the layer separation by minimizing a
      least-squares objective function. However, due to high noise levels and
      inaccurate motion estimates, the results are not satisfactory in X-ray images. In
      this work, we propose a probabilistic model for motion layer separation. In this
      model, we analyze various data terms and regularization terms theoretically and
      experimentally. We show that a robust penalty function is required in the data
      term to deal with noise and shortcomings of the image formation model. For the
      regularization term, we propose to enforce smoothness of the layers using
      bilateral total variation. On synthetic data, the mean squared error between the
      estimated layers and the ground truth is improved by 18% compared to the state of
      the art. In addition, we show qualitative improvements on real X-ray data.

PMID- 26221682
TI  - Weighted Hashing with Multiple Cues for Cell-Level Analysis of Histopathological
      Images.
AB  - Recently, content-based image retrieval has been investigated for
      histopathological image analysis, focusing on improving the accuracy and
      scalability. The main motivation is to interpret a new image (i.e., query image)
      by searching among a potentially large-scale database of training images in real
      time. Hashing methods have been employed because of their promising performance.
      However, most previous works apply hashing algorithms on the whole images, while
      the important information of histopathological images usually lies in individual
      cells. In addition, they usually only hash one type of features, even though it
      is often necessary to inspect multiple cues of cells. Therefore, we propose a
      probabilistic-based hashing framework to model multiple cues of cells for
      accurate analysis of histopathological images. Specifically, each cue of a cell
      is compressed as binary codes by kernelized and supervised hashing, and the
      importance of each hash entry is determined adaptively according to its
      discriminativity, which can be represented as probability scores. Given these
      scores, we also propose several feature fusion and selection schemes to integrate
      their strengths. The classification of the whole image is conducted by
      aggregating the results from multiple cues of all cells. We apply our algorithm
      on differentiating adenocarcinoma and squamous carcinoma, i.e., two types of lung
      cancers, using a large dataset containing thousands of lung microscopic tissue
      images. It achieves 90.3% accuracy by hashing and retrieving multiple cues of
      half-million cells.

PMID- 26221683
TI  - Multiresolution Diffeomorphic Mapping for Cortical Surfaces.
AB  - Due to the convoluted folding pattern of the cerebral cortex, accurate alignment
      of cortical surfaces remains challenging. In this paper, we present a
      multiresolution diffeomorphic surface mapping algorithm under the framework of
      large deformation diffeomorphic metric mapping (LDDMM). Our algorithm takes
      advantage of multiresolution analysis (MRA) for surfaces and constructs cortical
      surfaces at multiresolution. This family of multiresolution surfaces are used as
      natural sparse priors of the cortical anatomy and provide the anchor points where
      the parametrization of deformation vector fields is supported. This naturally
      constructs tangent bundles of diffeomorphisms at different resolution levels and
      hence generates multiresolution diffeomorphic transformation. We show that our
      construction of multiresolution LDDMM surface mapping can potentially reduce
      computational cost and improves the mapping accuracy of cortical surfaces.

PMID- 26221684
TI  - A Comprehensive Computer-Aided Polyp Detection System for Colonoscopy Videos.
AB  - Computer-aided detection (CAD) can help colonoscopists reduce their polyp miss
      rate, but existing CAD systems are handicapped by using either shape, texture, or
      temporal information for detecting polyps, achieving limited sensitivity and
      specificity. To overcome this limitation, our key contribution of this paper is
      to fuse all possible polyp features by exploiting the strengths of each feature
      while minimizing its weaknesses. Our new CAD system has two stages, where the
      first stage builds on the robustness of shape features to reliably generate a set
      of candidates with a high sensitivity, while the second stage utilizes the high
      discriminative power of the computationally expensive features to effectively
      reduce false positives. Specifically, we employ a unique edge classifier and an
      original voting scheme to capture geometric features of polyps in context and
      then harness the power of convolutional neural networks in a novel score fusion
      approach to extract and combine shape, color, texture, and temporal information
      of the candidates. Our experimental results based on FROC curves and a new
      analysis of polyp detection latency demonstrate a superiority over the state-of
      the-art where our system yields a lower polyp detection latency and achieves a
      significantly higher sensitivity while generating dramatically fewer false
      positives. This performance improvement is attributed to our reliable candidate
      generation and effective false positive reduction methods.

PMID- 26221685
TI  - A Feature-Based Approach to Big Data Analysis of Medical Images.
AB  - This paper proposes an inference method well-suited to large sets of medical
      images. The method is based upon a framework where distinctive 3D scale-invariant
      features are indexed efficiently to identify approximate nearest-neighbor (NN)
      feature matches-in O (log N) computational complexity in the number of images N.
      It thus scales well to large data sets, in contrast to methods based on pair-wise
      image registration or feature matching requiring O(N) complexity. Our theoretical
      contribution is a density estimator based on a generative model that generalizes
      kernel density estimation and K-nearest neighbor (KNN) methods.. The estimator
      can be used for on-the-fly queries, without requiring explicit parametric models
      or an off-line training phase. The method is validated on a large multi-site data
      set of 95,000,000 features extracted from 19,000 lung CT scans. Subject-level
      classification identifies all images of the same subjects across the entire data
      set despite deformation due to breathing state, including unintentional duplicate
      scans. State-of-the-art performance is achieved in predicting chronic pulmonary
      obstructive disorder (COPD) severity across the 5-category GOLD clinical rating,
      with an accuracy of 89% if both exact and one-off predictions are considered
      correct.

PMID- 26221686
TI  - Joint Segmentation and Registration Through the Duality of Congealing and Maximum
      Likelihood Estimate.
AB  - In this paper we consider the task of joint registration and segmentation. A
      popular method which aligns images and simultaneously estimates a simple
      statistical shape model was proposed by E. Learned-Miller and is known
      as.congealing. It considers the entropy of a simple, pixel-wise independent
      distribution as the objective function for searching the unknown transformations.
      Besides being intuitive and appealing, this idea raises several theoretical and
      practical questions, which we try to answer in this paper. First, we analyse the
      approach theoretically and show that the original congealing is in fact the DC
      dual task (difference of convex functions) for a properly formulated Maximum
      Likelihood estimation task. This interpretation immediately leads to a different
      choice for the algorithm which is substantially simpler than the known congealing
      algorithm. The second contribution is to show, how to generalise the task for
      models in which the shape prior is formulated in terms of segmentation labellings
      and is related to the signal domain via a parametric appearance model. We call
      this generalisation unsupervised congealing. The new approach is applied to the
      task of aligning and segmenting imaginal discs of Drosophila melanogaster larvae.

PMID- 26221687
TI  - Self-Aligning Manifolds for Matching Disparate Medical Image Datasets.
AB  - Manifold alignment can be used to reduce the dimensionality of multiple medical
      image datasets into a single globally consistent low-dimensional space. This may
      be desirable in a wide variety of problems, from fusion of different imaging
      modalities for Alzheimer's disease classification to 4DMR reconstruction from 2D
      MR slices. Unfortunately, most existing manifold alignment techniques require
      either a set of prior correspondences or comparability between the datasets in
      high-dimensional space, which is often not possible. We propose a novel technique
      for the 'self-alignment' of manifolds (SAM) from multiple dissimilar imaging
      datasets without prior correspondences or inter-dataset image comparisons. We
      quantitatively evaluate the method on 4DMR reconstruction from realistic,
      synthetic sagittal 2D MR slices from 6 volunteers and real data from 4
      volunteers. Additionally, we demonstrate the technique for the compounding of two
      free breathing 3D ultrasound views from one volunteer. The proposed method
      performs significantly better for 4DMR reconstruction than state-of-the-art image
      based techniques.

PMID- 26221688
TI  - Leveraging EAP-Sparsity for Compressed Sensing of MS-HARDI in (k, q)-Space.
AB  - Compressed Sensing (CS) for the acceleration of MR scans has been widely
      investigated in the past decade. Lately, considerable progress has been made in
      achieving similar speed ups in acquiring multi-shell high angular resolution
      diffusion imaging (MS-HARDI) scans. Existing approaches in this context were
      primarily concerned with sparse reconstruction of the diffusion MR signal S(q) in
      the q-space. More recently, methods have been developed to apply the compressed
      sensing framework to the 6-dimensional joint (k, q)-space, thereby exploiting the
      redundancy in this 6D space. To guarantee accurate reconstruction from partial MS
      HARDI data, the key ingredients of compressed sensing that need to be brought
      together are: (1) the function to be reconstructed needs to have a sparse
      representation, and (2) the data for reconstruction ought to be acquired in the
      dual domain (i.e., incoherent sensing) and (3) the reconstruction process
      involves a (convex) optimization. In this paper, we present a novel approach that
      uses partial Fourier sensing in the 6D space of (k, q) for the reconstruction of
      P(x, r). The distinct feature of our approach is a sparsity model that leverages
      surfacelets in conjunction with total variation for the joint sparse
      representation of P(x, r). Thus, our method stands to benefit from the practical
      guarantees for accurate reconstruction from partial (k, q)-space data. Further,
      we demonstrate significant savings in acquisition time over diffusion spectral
      imaging (DSI) which is commonly used as the benchmark for comparisons in reported
      literature. To demonstrate the benefits of this approach,.we present several
      synthetic and real data examples.

PMID- 26221689
TI  - Multi-stage Biomarker Models for Progression Estimation in Alzheimer's Disease.
AB  - The estimation of disease progression in Alzheimer's disease (AD) based on a
      vector of quantitative biomarkers is of high interest to clinicians, patients,
      and biomedical researchers alike. In this work, quantile regression is employed
      to learn statistical models describing the evolution of such biomarkers. Two
      separate models are constructed using (1) subjects that progress from a
      cognitively normal (CN) stage to mild cognitive impairment (MCI) and (2) subjects
      that progress from MCI to AD during the observation window of a longitudinal
      study. These models are then automatically combined to develop a multi-stage
      disease progression model for the whole disease course. A probabilistic approach
      is derived to estimate the current disease progress (DP) and the disease
      progression rate (DPR) of a given individual by fitting any acquired biomarkers
      to these models. A particular strength of this method is that it is applicable
      even if individual biomarker measurements are missing for the subject. Employing
      cognitive scores and image-based biomarkers, the presented method is used to
      estimate DP and DPR for subjects from the Alzheimer's Disease Neuroimaging
      Initiative (ADNI). Further, the potential use of these values as features for
      different classification tasks is demonstrated. For example, accuracy of 64% is
      reached for CN vs. MCI vs. AD classification.

PMID- 26221690
TI  - Measuring Asymmetric Interactions in Resting State Brain Networks.
AB  - Directed graph representations of brain networks are increasingly being used to
      indicate the direction and level of influence among brain regions. Most of the
      existing techniques for directed graph representations are based on time series
      analysis and the concept of causality, and use time lag information in the brain
      signals. These time lag-based techniques can be inadequate for functional
      magnetic resonance imaging (fMRI) signal analysis due to the limited time
      resolution of fMRI as well as the low frequency hemodynamic response. The aim of
      this paper is to present a novel measure of necessity that uses asymmetry in the
      joint distribution of brain activations to infer the direction and level of
      interaction among brain regions. We present a mathematical formula for computing
      necessity and extend this measure to partial necessity, which can potentially
      distinguish between direct and indirect interactions. These measures do not
      depend on time lag for directed modeling of brain interactions and therefore are
      more suitable for fMRI signal analysis. The necessity measures were used to
      analyze resting state fMRI data to determine the presence of hierarchy and
      asymmetry of brain interactions during resting state. We performed ROI-wise
      analysis using the proposed necessity measures to study the default mode network.
      The empirical joint distribution of the fMRI signals was determined using kernel
      density estimation, and was used for computation of the necessity and partial
      necessity measures. The significance of these measures was determined using a one
      sided Wilcoxon rank-sum test. Our results are consistent with the hypothesis that
      the posterior cingulate cortex plays a central role in the default mode network.

PMID- 26221691
TI  - Shape Classification Using Wasserstein Distance for Brain Morphometry Analysis.
AB  - Brain morphometry study plays a fundamental role in medical imaging analysis and
      diagnosis. This work proposes a novel framework for brain cortical surface
      classification using Wasserstein distance, based on uniformization theory and
      Riemannian optimal mass transport theory. By Poincare uniformization theorem, all
      shapes can be conformally deformed to one of the three canonical spaces: the unit
      sphere, the Euclidean plane or the hyperbolic plane. The uniformization map will
      distort the surface area elements. The area-distortion factor gives a probability
      measure on the canonical uniformization space. All the probability measures on a
      Riemannian manifold form the Wasserstein space. Given any 2 probability measures,
      there is a unique optimal mass transport map between them, the transportation
      cost defines the Wasserstein distance between them. Wasserstein distance gives a
      Riemannian metric for the Wasserstein space. It intrinsically measures the
      dissimilarities between shapes and thus has the potential for shape
      classification. To the best of our knowledge, this is the first. work to
      introduce the optimal mass transport map to general Riemannian manifolds. The
      method is based on geodesic power Voronoi diagram. Comparing to the conventional
      methods, our approach solely depends on Riemannian metrics and is invariant under
      rigid motions and scalings, thus it intrinsically measures shape distance.
      Experimental results on classifying brain cortical surfaces with different
      intelligence quotients demonstrated the efficiency and efficacy of our method.

PMID- 26221693
TI  - Predicting Semantic Descriptions from Medical Images with Convolutional Neural
      Networks.
AB  - Learning representative computational models from medical imaging data requires
      large training data sets. Often, voxel-level annotation is unfeasible for
      sufficient amounts of data. An alternative to manual annotation, is to use the
      enormous amount of knowledge encoded in imaging data and corresponding reports
      generated during clinical routine. Weakly supervised learning approaches can link
      volume-level labels to image content but suffer from the typical label
      distributions in medical imaging data where only a small part consists of
      clinically relevant abnormal structures. In this paper we propose to use a
      semantic representation of clinical reports as a learning target that is
      predicted from imaging data by a convolutional neural network. We demonstrate how
      we can learn accurate voxel-level classifiers based on weak volume-level semantic
      descriptions on a set of 157 optical coherence tomography (OCT) volumes. We
      specifically show how semantic information increases classification accuracy for
      intraretinal cystoid fluid (IRC), subretinal fluid (SRF) and normal retinal
      tissue, and how the learning algorithm links semantic concepts to image content
      and geometry.

PMID- 26221692
TI  - Temporal Trajectory and Progression Score Estimation from Voxelwise Longitudinal
      Imaging Measures: Application to Amyloid Imaging.
AB  - Abstract. Cortical beta-amyloid deposition begins in Alzheimer's disease (AD)
      years before the onset of any clinical symptoms. It is therefore important to
      determine the temporal trajectories of amyloid deposition in these earliest
      stages in order to better understand their associations with progression to AD. A
      method for estimating the temporal trajectories of voxelwise amyloid as measured
      using longitudinal positron emission tomography (PET) imaging is presented. The
      method involves the estimation of a score for each subject visit based on the PET
      data that reflects their amyloid progression. This amyloid progression score
      allows subjects with similar progressions to be aligned and analyzed together.
      The estimation of the progression scores and the amyloid trajectory parameters
      are performed using an expectation-maximization algorithm. The correlations among
      the voxel measures of amyloid are modeled to reflect the spatial nature of PET
      images. Simulation results show that model parameters are captured well at a
      variety of noise and spatial correlation levels. The method is applied to
      longitudinal amyloid imaging data considering each cerebral hemisphere
      separately. The results are consistent across the hemispheres and agree with a
      global index of brain amyloid known as mean cortical DVR. Unlike mean cortical
      DVR, which depends on a priori defined regions, the progression score extracted
      by the method is data-driven and does not make assumptions about regional
      longitudinal changes. Compared to regressing on age at each voxel, the
      longitudinal trajectory slopes estimated using the proposed method show better
      localized longitudinal changes.

PMID- 26221694
TI  - Bodypart Recognition Using Multi-stage Deep Learning.
AB  - Automatic medical image analysis systems often start from identifying the human
      body part contained in the image; Specifically, given a transversal slice, it is
      important to know which body part it comes from, namely "slice-based bodypart
      recognition". This problem has its unique characteristic--the body part of a
      slice is usually identified by local discriminative regions instead of global
      image context, e.g., a cardiac slice is differentiated from an aorta arch slice
      by the mediastinum region. To leverage this characteristic, we design a multi
      stage deep learning framework that aims at: (1) discover the local regions that
      are discriminative to the bodypart recognition, and (2) learn a bodypart
      identifier based on these local regions. These two tasks are achieved by the two
      stages of our learning scheme, respectively. In the pre-train stage, a
      convolutional neural network (CNN) is learned in a multi-instance learning
      fashion to extract the most discriminative local patches from the training
      slices. In the boosting stage, the learned CNN is further boosted by these local
      patches for bodypart recognition. By exploiting the discriminative local
      appearances, the learned CNN becomes more accurate than global image context
      based approaches. As a key hallmark, our method does not require manual
      annotations of the discriminative local patches. Instead, it automatically
      discovers them through multi-instance deep learning. We validate our method on a
      synthetic dataset and a large scale CT dataset (7000+ slices from wholebody CT
      scans). Our method achieves better performances than state-of-the-art approaches,
      including the standard CNN.

PMID- 26221695
TI  - Multi-subject Manifold Alignment of Functional Network Structures via Joint
      Diagonalization.
AB  - Functional magnetic resonance imaging group studies rely on the ability to
      establish correspondence across individuals. This enables location specific
      comparison of functional brain characteristics. Registration is often based on
      morphology and does not take variability of functional localization into account.
      This can lead to a loss of specificity, or confounds when studying diseases. In
      this paper we propose multi-subject functional registration by manifold alignment
      via coupled joint diagonalization. The functional network structure of each
      subject is encoded in a diffusion map, where functional relationships are
      decoupled from spatial position. Two-step manifold alignment estimates initial
      correspondences between functionally equivalent regions. Then, coupled joint
      diagonalization establishes common eigenbases across all individuals, and refines
      the functional correspondences. We evaluate our approach on fMRI data acquired
      during a language paradigm. Experiments demonstrate the benefits in matching
      accuracy achieved by coupled joint diagonalization compared to previously
      proposed functional alignment approaches, or alignment based on structural
      correspondences.

PMID- 26221696
TI  - Brain Transfer: Spectral Analysis of Cortical Surfaces and Functional Maps.
AB  - The study of brain functions using fMRI often requires an accurate alignment of
      cortical data across a population. Particular challenges are surface inflation
      for cortical visualizations and measurements, and surface matching or alignment
      of functional data on surfaces for group-level analyses. Present methods
      typically treat each step separately and can be computationally expensive. For
      instance, smoothing and matching of cortices often require several hours.
      Conventional methods also rely on anatomical features to drive the alignment of
      functional data between cortices, whereas anatomy and function can vary across
      individuals. To address these issues, we propose BrainTransfer, a spectral
      framework that unifies cortical smoothing, point matching with confidence
      regions, and transfer of functional maps, all within minutes of computation.
      Spectral methods decompose shapes into intrinsic geometrical harmonics, but
      suffer from the inherent instability of eigenbasis. This limits their accuracy
      when matching eigenbasis, and prevents the spectral transfer of functions. Our
      contributions consist of, first, the optimization of a spectral transformation
      matrix, which combines both, point correspondence and change of eigenbasis, and
      second, focused harmonics, which localize the spectral decomposition of
      functional data. BrainTransfer enables the transfer of surface functions across
      interchangeable cortical spaces, accounts for localized confidence, and gives a
      new way to perform statistics directly on surfaces. Benefits of spectral
      transfers are illustrated with a variability study on shape and functional data.
      Matching accuracy on retinotopy is increased over conventional methods.

PMID- 26221697
TI  - Finding a Path for Segmentation Through Sequential Learning.
AB  - Sequential learning techniques, such as auto-context, that applies the output of
      an intermediate classifier as contextual features for its subsequent classifier
      has shown impressive performance for semantic segmentation. We show that these
      methods can be interpreted as an approximation technique derived from a Bayesian
      formulation. To improve the effectiveness of applying this approximation
      technique, we propose a new sequential learning approach for semantic
      segmentation that solves a segmentation problem by breaking it into a series of
      simplified segmentation problems. Sequentially solving each of the simplified
      problems along the path leads to a more effective way for solving the original
      segmentation problem. To achieve this goal, we also propose a learning-based
      method to generate simplified segmentation problems by explicitly controlling the
      complexities of the modeling classifiers. We report promising results on the 2013
      SATA canine leg muscle segmentation dataset.

PMID- 26221698
TI  - Pancreatic Tumor Growth Prediction with Multiplicative Growth and Image-Derived
      Motion.
AB  - Pancreatic neuroendocrine tumors are abnormal growths of hormone-producing cells
      in the pancreas. Different from the brain in the skull, the pancreas in the
      abdomen can be largely deformed by the body posture and the surrounding organs.
      In consequence, both tumor growth and pancreatic motion attribute to the tumor
      shape difference observable from images. As images at different time points are
      used to personalize the tumor growth model, the prediction accuracy may be
      reduced if such motion is ignored. Therefore, we incorporate the image-derived
      pancreatic motion to tumor growth personalization. For realistic mechanical
      interactions, the multiplicative growth decomposition is used with a hyperelastic
      constitutive law to model tumor mass effect, which allows growth modeling without
      compromising the mechanical accuracy. With also the FDG-PET and contrast-enhanced
      CT images, the functional, structural, and motion data are combined for a more
      patient-specific model. Experiments on synthetic and clinical data show the
      importance of image-derived motion on estimating physiologically plausible
      mechanical properties and the promising performance of our framework. From six
      patient data sets, the recall, precision, Dice coefficient, relative volume
      difference, and average surface distance were 89.8 +/- 3.5%, 85.6 +/- 7.5%, 87.4
      +/- 3.6%, 9.7 +/- 7.2%, and 0.6 +/- 0.2 mm, respectively.

PMID- 26221699
TI  - IMaGe: Iterative Multilevel Probabilistic Graphical Model for Detection and
      Segmentation of Multiple Sclerosis Lesions in Brain MRI.
AB  - In this paper, we present IMaGe, a new, iterative two-stage probabilistic
      graphical model for detection and segmentation of Multiple Sclerosis (MS)
      lesions. Our model includes two levels of Markov Random Fields (MRFs). At the
      bottom level, a regular grid voxel-based MRF identifies potential lesion voxels,
      as well as other tissue classes, using local and neighbourhood intensities and
      class priors. Contiguous voxels of a particular tissue type are grouped into
      regions. A higher, non-lattice MRF is then constructed, in which each node
      corresponds to a region, and edges are defined based on neighbourhood
      relationships between regions. The goal of this MRF is to evaluate the
      probability of candidate lesions, based on group intensity, texture and
      neighbouring regions. The inferred information is then propagated to the voxel
      level MRF. This process of iterative inference between the two levels repeats as
      long as desired. The iterations suppress false positives and refine lesion
      boundaries. The framework is trained on 660 MRI volumes of MS patients enrolled
      in clinical trials from 174 different centres, and tested on a separate multi
      centre clinical trial data set with 535 MRI volumes. All data consists of T1, T2,
      PD and FLAIR contrasts. In comparison to other MRF methods, such as, and a
      traditional MRF, IMaGe is much more sensitive (with slightly better PPV). It
      outperforms its nearest competitor by around 20% when detecting very small
      lesions (3-10 voxels). This is a significant result, as such lesions constitute
      around 40% of the total number of lesions.

PMID- 26221700
TI  - Moving Frames for Heart Fiber Reconstruction.
AB  - The method of moving frames provides powerful geometrical tools for the analysis
      of smoothly varying frame fields. However, in the face of missing measurements, a
      reconstruction problem arises, one that is largely unexplored for 3D frame
      fields. Here we consider the particular example of reconstructing impaired
      cardiac diffusion magnetic resonance imaging (dMRI) data. We combine moving frame
      analysis with a diffusion inpainting scheme that incorporates rule-based priors.
      In contrast to previous reconstruction methods, this new approach uses
      comprehensive differential descriptors for cardiac fibers, and is able to fully
      recover their orientation. We demonstrate the superior performance of this
      approach in terms of error of fit when compared to alternate methods. We
      anticipate that these tools could find application in clinical settings, where
      damaged heart tissue needs to be replaced or repaired, and for generating dense
      fiber volumes in electromechanical modelling of the heart.

PMID- 26221701
TI  - Detail-Preserving PET Reconstruction with Sparse Image Representation and
      Anatomical Priors.
AB  - Positron emission tomography (PET) reconstruction is an ill-posed inverse problem
      which typically involves fitting a high-dimensional forward model of the imaging
      process to noisy, and sometimes undersampled photon emission data. To improve the
      image quality, prior information derived from anatomical images of the same
      subject has been previously used in the penalised maximum likelihood (PML) method
      to regularise the model complexity and selectively smooth the image on a voxel
      basis in PET reconstruction. In this work, we propose a novel perspective of
      incorporating the prior information by exploring the sparse property of natural
      images. Instead of a regular voxel grid, the sparse image representation jointly
      determined by the prior image and the PET data is used in reconstruction to
      leverage between the image details and smoothness, and this prior is integrated
      into the PET forward model and has a closed-form expectation maximisation (EM)
      solution. Simulations show that the proposed approach achieves improved bias
      versus variance trade-off and higher contrast recovery than the current state-of
      the-art methods, and preserves the image details better. Application to clinical
      PET data shows promising results.

PMID- 26221702
TI  - Automatic Detection of the Uterus and Fallopian Tube Junctions in Laparoscopic
      Images.
AB  - We present a method for the automatic detection of the uterus and the Fallopian
      tube/Uterus junctions (FU-junctions) in a monocular laparoscopic image. The main
      application is to perform automatic registration and fusion between preoperative
      radiological images of the uterus and laparoscopic images for image-guided
      surgery. In the broader context of computer assisted intervention, our method is
      the first that detects an organ and registration landmarks from laparoscopic
      images without manual input. Our detection problem is challenging because of the
      large inter-patient anatomical variability and pathologies such as uterine
      fibroids. We solve the problem using learned contextual geometric constraints
      that statistically model the positions and orientations of the FU-junctions
      relative to the uterus' body. We train the uterus detector using a modern part
      based approach and the FU-junction detector using junction-specific context
      sensitive features. We have trained and tested on a database of 95 uterus images
      with cross validation, and successfully detected the uterus with Recall = 0.95
      and average Number of False Positives per Image (NFPI) = 0.21, and FU-junctions
      with Recall = 0.80 and NFPI = 0.50. Our experimental results show that the
      contextual constraints are fundamental to achieve high quality detection.

PMID- 26221703
TI  - A Mixed-Effects Model with Time Reparametrization for Longitudinal Univariate
      Manifold-Valued Data.
AB  - Mixed-effects models provide a rich theoretical framework for the analysis of
      longitudinal data. However, when used to analyze or predict the progression of a
      neurodegenerative disease such as Alzheimer's disease, these models usually do
      not take into account the fact that subjects may be at different stages of
      disease progression and the interpretation of the model may depend on some
      implicit reference time. In this paper, we propose a generative statistical model
      for longitudinal data, described in a univariate Riemannian manifold setting,
      which estimates an average disease progression model, subject-specific time
      shifts and acceleration factors. The time shifts account for variability in age
      at disease-onset time. The acceleration factors account for variability in speed
      of disease progression. For a given individual, the estimated time shift and
      acceleration factor define an affine reparametrization of the average disease
      progression model. This statistical model has been used to analyze
      neuropsychological assessments scores and cortical thickness measurements from
      the Alzheimer's Disease Neuroimaging Initiative database. The numerical results
      showed that we can distinguish between slow versus fast progressing and early
      versus late-onset individuals.

PMID- 26221704
TI  - Prediction of Longitudinal Development of Infant Cortical Surface Shape Using a
      4D Current-Based Learning Framework.
AB  - Understanding the early dynamics of the highly folded human cerebral cortex is
      still an actively evolving research field teeming with unanswered questions.
      Longitudinal neuroimaging analysis and modeling have become the new trend to
      advance research in this field. However, this is challenged by a limited number
      of acquisition timepoints and the absence of inter-subject matching between
      timepoints. In this paper, we propose a novel framework that unprecedentedly
      solves the problem of predicting the dynamic evolution of infant cortical surface
      shape solely from a single baseline shape based on a spatiotemporal (4D) current
      based learning approach. Specifically, our method learns from longitudinal data
      both the geometric (vertices positions) and dynamic (temporal evolution
      trajectories) features of the infant cortical surface, comprising a training
      stage and a prediction stage. In the training stage, we first use the current
      based shape regression model to set up the inter-subject cortical surface
      correspondences at baseline of all training subjects. We then estimate for each
      training subject the diffeomorphic temporal evolution trajectories of the
      cortical surface shape and build an empirical mean spatiotemporal surface atlas.
      In the prediction stage, given an infant, we first warp all training subjects
      onto its baseline cortical surface. Second, we select the most appropriate learnt
      features from training subjects to simultaneously predict the cortical surface
      shapes at all later timepoints from its baseline cortical surface, based on
      closeness metrics between this baseline surface and the learnt baseline
      population average surface atlas. We used the proposed framework to predict the
      inner cortical surface shape at 3, 6 and 9 months from the cortical shape at
      birth in 9 healthy infants. Our method predicted with good accuracy the
      spatiotemporal dynamic change of the highly folded cortex.

PMID- 26221705
TI  - Multi-scale Convolutional Neural Networks for Lung Nodule Classification.
AB  - We investigate the problem of diagnostic lung nodule classification using
      thoracic Computed Tomography (CT) screening. Unlike traditional studies primarily
      relying on nodule segmentation for regional analysis, we tackle a more
      challenging problem on directly modelling raw nodule patches without any prior
      definition of nodule morphology. We propose a hierarchical learning framework-
      Multi-scale Convolutional Neural Networks (MCNN)--to capture nodule heterogeneity
      by extracting discriminative features from alternatingly stacked layers. In
      particular, to sufficiently quantify nodule characteristics, our framework
      utilizes multi-scale nodule patches to learn a set of class-specific features
      simultaneously by concatenating response neuron activations obtained at the last
      layer from each input scale. We evaluate the proposed method on CT images from
      Lung Image Database Consortium and Image Database Resource Initiative (LIDC
      IDRI), where both lung nodule screening and nodule annotations are provided.
      Experimental results demonstrate the effectiveness of our method on classifying
      malignant and benign nodules without nodule segmentation.

PMID- 26221707
TI  - Illumination Compensation and Normalization Using Low-Rank Decomposition of
      Multispectral Images in Dermatology.
AB  - When attempting to recover the surface color from an image, modelling the
      illumination contribution per-pixel is essential. In this work we present a novel
      approach for illumination compensation using multispectral image data. This is
      done by means of a low-rank decomposition of representative spectral bands with
      prior knowledge of the reflectance spectra of the imaged surface. Experimental
      results on synthetic data, as well as on images of real lesions acquired at the
      university clinic, show that the proposed method significantly improves the
      contrast between the lesion and the background.

PMID- 26221706
TI  - Tractography-Driven Groupwise Multi-scale Parcellation of the Cortex.
AB  - The analysis of the connectome of the human brain provides key insight into the
      brain's organisation and function, and its evolution in disease or ageing.
      Parcellation of the cortical surface into distinct regions in terms of structural
      connectivity is an essential step that can enable such analysis. The estimation
      of a stable connectome across a population of healthy subjects requires the
      estimation of a groupwise parcellation that can capture the variability of the
      connectome across the population. This problem has solely been addressed in the
      literature via averaging of connectivity profiles or finding correspondences
      between individual parcellations a posteriori. In this paper, we propose a
      groupwise parcellation method of the cortex based on diffusion MR images (dMRI).
      We borrow ideas from the area of cosegmentation in computer vision and directly
      estimate a consistent parcellation across different subjects and scales through a
      spectral clustering approach. The parcellation is driven by the tractography
      connectivity profiles, and information between subjects and across scales.
      Promising qualitative and quantitative results on a sizeable data-set demonstrate
      the strong potential of the method.

PMID- 26221708
TI  - Efficient Gaussian Process-Based Modelling and Prediction of Image Time Series.
AB  - In this work we propose a novel Gaussian process-based spatio-temporal model of
      time series of images. By assuming separability of spatial and temporal processes
      we provide a very efficient and robust formulation for the marginal likelihood
      computation and the posterior prediction. The model adaptively accounts for local
      spatial correlations of the data, and the covariance structure is effectively
      parameterised by the Kronecker product of covariance matrices of very small size,
      each encoding only a single direction in space. We provide a simple and flexible
      framework for within- and between-subject modelling and prediction. In
      particular, we introduce the Hoffman-Ribak method for efficient inference on
      posterior processes and its uncertainty. The proposed framework is applied in the
      context of longitudinal modelling in Alzheimer's disease. We firstly demonstrate
      the advantage of our non-parametric method for modelling of within-subject
      structural changes. The results show that non-parametric methods demonstrably
      outperform conventional parametric methods. Then the framework is extended to
      optimize complex parametrized covariate kernels. Using Bayesian model comparison
      via marginal likelihood the framework enables to compare different hypotheses
      about individual change processes of images.

PMID- 26221709
TI  - A Simulation Framework for Quantitative Validation of Artefact Correction in
      Diffusion MRI.
AB  - In this paper we demonstrate a simulation framework that enables the direct and
      quantitative comparison of post-processing methods for diffusion weighted
      magnetic resonance (DW-MR) images. DW-MR datasets are employed in a range of
      techniques that enable estimates of local microstructure and global connectivity
      in the brain. These techniques require full alignment of images across the
      dataset, but this is rarely the case. Artefacts such as eddy-current (EC)
      distortion and motion lead to misalignment between images, which compromise the
      quality of the microstructural measures obtained from them. Numerous methods and
      software packages exist to correct these artefacts, some of which have become de
      facto standards, but none have been subject to rigorous validation. The ultimate
      aim of these techniques is improved image alignment, yet in the literature this
      is assessed using either qualitative visual measures or quantitative surrogate
      metrics. Here we introduce a simulation framework that allows for the direct,
      quantitative assessment of techniques, enabling objective comparisons of existing
      and future methods. DW-MR datasets are generated using a process that is based on
      the physics of MRI acquisition, which allows for the salient features of the
      images and their artefacts to be reproduced. We demonstrate the application of
      this framework by testing one of the most commonly used methods for EC
      correction, registration of DWIs to b = 0, and reveal the systematic bias this
      introduces into corrected datasets.

PMID- 26221710
TI  - Towards a Quantified Network Portrait of a Population.
AB  - Computational network analysis has enabled researchers to investigate patterns of
      interactions between anatomical regions of the brain. Identification of
      subnetworks of the human connectome can reveal how the network manages an
      interplay of the seemingly competing principles of functional segregation and
      integration. Despite the study of subnetworks of the human structural connectome
      by various groups, the level of expression of these subnetworks in each subject
      remains for the most part largely unexplored. Thus, there is a need for methods
      that can extract common subnetworks that together render a network portrait of a
      sample and facilitate analysis of the same, such as group comparisons based on
      the expression of the subnetworks in each subject. In this paper, we propose a
      framework for quantifying the subject-specific expression of subnetworks. Our
      framework consists of two parts, namely subnetwork detection and reconstructive
      projection onto subnetworks. The first part identifies subnetworks of the
      connectome using multi-view spectral clustering. The second part quantifies
      subject specific manifestations of these subnetworks by nonnegative matrix
      decomposition. Positivity constraint is imposed to treat each subnetwork as a
      structure depicting the connectivity between specific anatomical regions. We have
      assessed the applicability of the framework by delineating a network portrait of
      a clinical sample consisting of children affected by autism spectrum disorder
      (ASD), and a matched group of typically developing controls (TDCs). Subsequent
      statistical analysis on the intra- and inter-subnetwork connections, revealed
      decreased connectivity in ASD group between regions of social cognition,
      executive functions, and emotion processing.

PMID- 26221711
TI  - Segmenting the Brain Surface from CT Images with Artifacts Using Dictionary
      Learning for Non-rigid MR-CT Registration.
AB  - This paper presents a dictionary learning-based method to segment the brain
      surface in post-surgical CT images of epilepsy patients following surgical
      implantation of electrodes. Using the electrodes identified in the post
      implantation CT, surgeons require accurate registration with pre-implantation
      functional and structural MR imaging to guide surgical resection of epileptic
      tissue. In this work, we use a surface-based registration method to align the MR
      and CT brain surfaces. The key challenge here is not the registration, but rather
      the extraction of the cortical surface from the CT image, which includes missing
      parts of the skull and artifacts introduced by the electrodes. To segment the
      brain from these images, we propose learning a model of appearance that captures
      both the normal tissue and the artifacts found along this brain surface boundary.
      Using clinical data, we demonstrate that our method both accurately extracts the
      brain surface and better localizes electrodes than intensity-based rigid and non
      rigid registration methods.

PMID- 26221712
TI  - AxTract: Microstructure-Driven Tractography Based on the Ensemble Average
      Propagator.
AB  - We propose a novel method to simultaneously trace brain white matter (WM)
      fascicles and estimate WM microstructure characteristics. Recent advancements in
      diffusion-weighted imaging (DWI) allow multi-shell acquisitions with b-values of
      up to 10,000 s/mm2 in human subjects, enabling the measurement of the ensemble
      average propagator (EAP) at distances as short as 10 MUm. Coupled with continuous
      models of the full 3D DWI signal and the EAP such as Mean Apparent Propagator
      (MAP) MRI, these acquisition schemes provide unparalleled means to probe the WM
      tissue in vivo. Presently, there are two complementary limitations in
      tractography and microstructure measurement techniques. Tractography techniques
      are based on models of the DWI signal geometry without taking specific hypotheses
      of the WM structure. This hinders the tracing of fascicles through certain WM
      areas with complex organization such as branching, crossing, merging, and
      bottlenecks that are indistinguishable using the orientation-only part of the DWI
      signal. Microstructure measuring techniques, such as AxCaliber, require the
      direction of the axons within the probed tissue before the acquisition as well as
      the tissue to be highly organized. Our contributions are twofold. First, we
      extend the theoretical DWI models proposed by Callaghan et al. to characterize
      the distribution of axonal calibers within the probed tissue taking advantage of
      the MAP-MRI model. Second, we develop a simultaneous tractography and axonal
      caliber distribution algorithm based on the hypothesis that axonal caliber
      distribution varies smoothly along a WM fascicle. To validate our model we test
      it on insilico phantoms and on the HCP dataset.

PMID- 26221713
TI  - Sampling from Determinantal Point Processes for Scalable Manifold Learning.
AB  - High computational costs of manifold learning prohibit its application for large
      datasets. A common strategy to overcome this problem is to perform dimensionality
      reduction on selected landmarks and to successively embed the entire dataset with
      the Nystrom method. The two main challenges that arise are: (i) the landmarks
      selected in non-Euclidean geometries must result in a low reconstruction error,
      (ii) the graph constructed from sparsely sampled landmarks must approximate the
      manifold well. We propose to sample the landmarks from determinantal
      distributions on non-Euclidean spaces. Since current determinantal sampling
      algorithms have the same complexity as those for manifold learning, we present an
      efficient approximation with linear complexity. Further, we recover the local
      geometry after the sparsification by assigning each landmark a local covariance
      matrix, estimated from the original point set. The resulting neighborhood
      selection .based on the Bhattacharyya distance improves the embedding of sparsely
      sampled manifolds. Our experiments show a significant performance improvement
      compared to state-of-the-art landmark selection techniques on synthetic and
      medical data.

PMID- 26221714
TI  - Model-Based Estimation of Microscopic Anisotropy in Macroscopically Isotropic
      Substrates Using Diffusion MRI.
AB  - Non-invasive estimation of cell size and shape is a key challenge in diffusion
      MRI. Changes in cell size and shape discriminate functional areas in the brain
      and can highlight different degrees of malignancy in cancer tumours. Consequently
      various methods have emerged recently that aim to measure the microscopic
      anisotropy of porous media such as biological tissue and aim to reflect pore
      eccentricity, the simplest shape feature. However, current methods assume a
      substrate of identical pores, and are strongly influenced by non-trivial size
      distribution. This paper presents a model-based approach that provides estimates
      of pore size and shape from diffusion MRI data. The technique uses a geometric
      model of randomly oriented finite cylinders with gamma distributed radii. We use
      Monte Carlo simulation to generate synthetic data in substrates consisting of
      randomly oriented cuboids with various size distributions and eccentricities. We
      compare the sensitivity of single and double pulsed field gradient (sPFG and
      dPFG) sequences to the size distribution and eccentricity and further compare
      different protocols of dPFG sequences with parallel and/or perpendicular pairs of
      gradients. The key result demonstrates that this model-based approach can provide
      features of pore shape (specifically eccentricity) that are independent of the
      size distribution unlike previous attempts to characterise microscopic
      anisotropy. We show further that explicitly accounting for size distribution is
      necessary for accurate estimates of average size and eccentricity, and a model
      that assumes a single size fails to recover the ground truth values. We find the
      most accurate parameter estimates for dPFG sequences with mixed parallel and
      perpendicular gradients, nevertheless all other sequences, including sPFG, show
      sensitivity as well.

PMID- 26221715
TI  - Construction of An Unbiased Spatio-Temporal Atlas of the Tongue During Speech.
AB  - Quantitative characterization and comparison of tongue motion during speech and
      swallowing present fundamental challenges because of striking variations in
      tongue structure and motion across subjects. A reliable and objective description
      of the dynamics tongue motion requires the consistent integration of inter
      subject variability to detect the subtle changes in populations. To this end, in
      this work, we present an approach to constructing an unbiased spatio-temporal
      atlas of the tongue during speech for the first time, based on cine-MRI from
      twenty two normal subjects. First, we create a common spatial space using images
      from the reference time frame, a neutral position, in which the unbiased spatio
      temporal atlas can be created. Second, we transport images from all time frames
      of all subjects into this common space via the single transformation. Third, we
      construct atlases for each time frame via groupwise diffeomorphic registration,
      which serves as the initial spatio-temporal atlas. Fourth, we update the spatio
      temporal atlas by realigning each time sequence based on the Lipschitz norm on
      diffeomorphisms between each subject and the initial atlas. We evaluate and
      compare different configurations such as similarity measures to build the atlas.
      Our proposed method permits to accurately and objectively explain the main
      pattern of tongue surface motion.

PMID- 26221716
TI  - Tree-Encoded Conditional Random Fields for Image Synthesis.
AB  - Magnetic resonance imaging (MRI) is the dominant modality for neuroimaging in
      clinical and research domains. The tremendous versatility of MRI as a modality
      can lead to large variability in terms of image contrast, resolution, noise, and
      artifacts. Variability can also manifest itself as missing or corrupt imaging
      data. Image synthesis has been recently proposed to homogenize and/or enhance the
      quality of existing imaging data in order to make them more suitable as
      consistent inputs for processing. We frame the image synthesis problem as an
      inference problem on a 3-D continuous-valued conditional random field (CRF). We
      model the conditional distribution as a Gaussian by defining quadratic
      association and interaction potentials encoded in leaves of a regression tree.
      The parameters of these quadratic potentials are learned by maximizing the pseudo
      likelihood of the training data. Final synthesis is done by inference on this
      model. We applied this method to synthesize T2-weighted images from T1-weighted
      images, showing improved synthesis quality as compared to current image synthesis
      approaches. We also synthesized Fluid Attenuated Inversion Recovery (FLAIR)
      images, showing similar segmentations to those obtained from real FLAIRs.
      Additionally, we generated super-resolution FLAIRs showing improved segmentation.

PMID- 26221717
TI  - Coupled Stable Overlapping Replicator Dynamics for Multimodal Brain Subnetwork
      Identification.
AB  - Combining imaging modalities to synthesize their inherent strengths provides a
      promising means for improving brain subnetwork identification. We propose a
      multimodal integration technique based on a sex-differentiated formulation of
      replicator dynamics for identifying subnetworks of brain regions that exhibit
      high inter-connectivity both functionally and structurally. Our method has a
      number of desired properties, namely, it can operate on weighted graphs derived
      from functional magnetic resonance imaging (tMRI) and diffusion MRI (dMRI) data,
      allows for subnetwork overlaps, has an intrinsic criterion for setting the number
      of subnetworks, and provides statistical control on false node inclusion in the
      identified subnetworks via the incorporation of stability selection. We thus
      refer to our technique as coupled stable overlapping replicator dynamics (CSORD).
      On synthetic data, We demonstrate that CSORD achieves significantly higher
      subnetwork identification accuracy than state-of-the-art techniques. On real.
      data from the Human Connectome Project (HCP), we show that CSORD attains improved
      test-retest reliability on multiple network measures and superior task
      classification accuracy.

PMID- 26221718
TI  - Joint 6D k-q Space Compressed Sensing for Accelerated High Angular Resolution
      Diffusion MRI.
AB  - High Angular Resolution Diffusion Imaging (HARDI) avoids the Gaussian. diffusion
      assumption that is inherent in Diffusion Tensor Imaging (DTI), and is capable of
      characterizing complex white matter micro-structure with greater precision.
      However, HARDI methods such as Diffusion Spectrum Imaging (DSI) typically require
      significantly more signal measurements than DTI, resulting in prohibitively long
      scanning times. One of the goals in HARDI research is therefore to improve
      estimation of quantities such as the Ensemble Average Propagator (EAP) and the
      Orientation Distribution Function (ODF) with a limited number of diffusion
      weighted measurements. A popular approach to this problem, Compressed Sensing
      (CS), affords highly accurate signal reconstruction using significantly fewer
      (sub-Nyquist) data points than required traditionally. Existing approaches to CS
      diffusion MRI (CS-dMRI) mainly focus on applying CS in the q-space of diffusion
      signal measurements and fail to take into consideration information redundancy in
      the k-space. In this paper, we propose a framework, called 6-Dimensional
      Compressed Sensing diffusion MRI (6D-CS-dMRI), for reconstruction of the
      diffusion signal and the EAP from data sub-sampled in both 3D k-space and 3D q
      space. To our knowledge, 6D-CS-dMRI is the first work that applies compressed
      sensing in the full 6D k-q space and reconstructs the diffusion signal in the
      full continuous q-space and the EAP in continuous displacement space.
      Experimental results on synthetic and real data demonstrate that, compared with
      full DSI sampling in k-q space, 6D-CS-dMRI yields excellent diffusion signal and
      EAP reconstruction with low root-mean-square error (RMSE) using 11 times less
      samples (3-fold reduction in k-space and 3.7-fold reduction in q-space).

PMID- 26221719
TI  - PoopMD, a Mobile Health Application, Accurately Identifies Infant Acholic Stools.
AB  - Biliary atresia (BA) is the leading cause of pediatric end-stage liver disease in
      the United States. Education of parents in the perinatal period with stool cards
      depicting acholic and normal stools has been associated with improved time-to
      diagnosis and survival in BA. PoopMD is a mobile application that utilizes a
      smartphone's camera and color recognition software to analyze an infant's stool
      and determine if additional follow-up is indicated. PoopMD was developed using
      custom HTML5/CSS3 and wrapped to work on iOS and Android platforms. In order to
      define the gold standard regarding stool color, seven pediatricians were asked to
      review 45 photographs of infant stool and rate them as acholic, normal, or
      indeterminate. Samples for which 6+ pediatricians demonstrated agreement defined
      the gold standard, and only these samples were included in the analysis. Accuracy
      of PoopMD was assessed using an iPhone 5s with incandescent lighting. Variability
      in analysis of stool photographs as acholic versus normal with intermediate
      rating weighted as 50% agreement (kappa) was compared between three laypeople and
      one expert user. Variability in output was also assessed between an iPhone 5s and
      a Samsung Galaxy S4, as well as between incandescent lighting and compact
      fluorescent lighting. Six-plus pediatricians agreed on 27 normal and 7 acholic
      photographs; no photographs were defined as indeterminate. The sensitivity was
      7/7 (100%). The specificity was 24/27 (89%) with 3/27 labeled as indeterminate;
      no photos of normal stool were labeled as acholic. The Laplace-smoothed positive
      likelihood ratio was 6.44 (95% CI 2.52 to 16.48) and the negative likelihood
      ratio was 0.13 (95% CI 0.02 to 0.83). kappauser was 0.68, kappaphone was 0.88,
      and kappalight was 0.81. Therefore, in this pilot study, PoopMD accurately
      differentiates acholic from normal color with substantial agreement across users,
      and almost perfect agreement across two popular smartphones and ambient light
      settings. PoopMD may be a valuable tool to help parents identify acholic stools
      in the perinatal period, and provide guidance as to whether additional evaluation
      with their pediatrician is indicated. PoopMD may improve outcomes for children
      with BA. 

PMID- 26221720
TI  - Anthropometric and Three-Compartment Body Composition Differences between Super
      League and Championship Rugby League Players: Considerations for the 2015 Season
      and Beyond.
AB  - Super League (SL) and Championship (RLC) rugby league players will compete
      against each other in 2015 and beyond. To identify possible discrepancies, this
      study compared the anthropometric profile and body composition of current SL
      (full-time professional) and RLC (part-time semi-professional) players using dual
      energy X-ray absorptiometry (DXA). A cross-sectional design involved DXA scans on
      67 SL (n=29 backs, n=38 forwards) and 46 RLC (n=20 backs, n=26 forwards) players
      during preseason. A one-way ANOVA was used to compare age, stature, body mass,
      soft tissue fat percentage, bone mineral content (BMC), total and regional (i.e.,
      arms, legs and trunk) fat and lean mass between SL forwards, SL backs, RLC
      forwards and RLC backs. No significant differences in age, stature or body mass
      were observed. SL forwards and backs had relatively less soft tissue fat (17.5 +/
      3.7 and 14.8 +/- 3.6 vs. 21.4 +/- 4.3 and 20.8 +/- 3.8%), greater BMC (4,528 +/-
      443 and 4,230 +/- 447 vs. 4,302 +/- 393 and 3,971 +/- 280 g), greater trunk lean
      mass (37.3 +/- 3.0 and 35.3 +/- 3.8 vs. 34.9 +/- 32.3 and 32.3 +/- 2.6 kg) and
      less trunk fat mass (8.5 +/- 2.7 and 6.2 +/- 2.1 vs. 10.7 +/- 2.8 and 9.5 +/- 2.9
      kg) than RLC forwards and backs. Observed differences may reflect selection based
      on favourable physical attributes, or training adaptations. To reduce this
      discrepancy, some RLC players should reduce fat mass and increase lean mass,
      which may be of benefit for the 2015 season and beyond. 

PMID- 26221721
TI  - First Case Genotype 4 Hepatitis E Infection After a Liver Transplant.
AB  - Chronic hepatitis in immunosuppressed patients because of infection with
      hepatitis E virus is increasingly recognized, but there is a paucity of knowledge
      about hepatitis E virus infection in solid-organ transplant recipients. Herein,
      we reported the first confirmatory case of hepatitis E virus genotype 4 infection
      in a 47-year-old woman who underwent a liver transplant recipient in Taiwan. The
      patient presented with unexplained hepatitis and severe jaundice. Hepatitis E
      virus RNA was present in serum and identified as the genotype 4 by reverse
      transcription polymerase chain reaction. Pathological findings revealed that
      prominent zone 3 canalicular and hepatocellular cholestasis with a few
      acidophilic bodies and giant cell transformation, which was typical of hepatitis
      E virus hepatitis. Even undergoing ribavirin treatment, she had worse cholestasis
      and recurrent urinary tract infections. She died from encephalopathy and sepsis 6
      months after the initial presentation. So far, compared with genotype 3 hepatitis
      E virus hepatitis, genotype 4 hepatitis E virus infection in solid-organ
      transplant recipients has been reported less frequently in the literature, and
      that warrants further accumulation of experiences.

PMID- 26221722
TI  - Transcriptional Analysis of MexAB-OprM Efflux Pumps System of Pseudomonas
      aeruginosa and Its Role in Carbapenem Resistance in a Tertiary Referral Hospital
      in India.
AB  - Carbapenem resistance presents severe threat to the treatment of multidrug
      resistant Pseudomonas aeruginosa infections. The study was undertaken to
      investigate the role of efflux pumps in conferring meropenem resistance and
      effect of single dose exposure of meropenem on transcription level of mexA gene
      in clinical isolates of P. aeruginosa from a tertiary referral hospital of India.
      Further, in this investigation an effort was made to assess whether different
      components of MexAB-OprM operon expresses in the same manner and the extent of
      contributions of those components in meropenem resistance in its natural host (P.
      aeruginosa) and in a heterologous host (E. coli). Out of 83 meropenem
      nonsusceptible isolates, 22 isolates were found to possess efflux pump activity
      phenotypically. Modified hodge test and multiplex PCR confirmed the absence of
      carbapenemase genes in those isolates. All of them were of multidrug resistant
      phenotype and were resistant to all the carbepenem drug tested. MexAB-OprM efflux
      pump was found to be overexpressed in all the study isolates. It could be
      observed that single dose exposure meropenem could give rise to trivial increase
      in transcription of mexA gene. Different constructs of MexAB-OprM (mexR-mexA-mexB
      OprM; mexA-mexB-OprM; mexA-mexB) could be expressed in both its natural (P.
      aeruginosa PAO1) and heterologous host (E. coli JM107) but transcription level of
      mexA gene varied in both the hosts before and after single dose exposure of
      meropenem. Different components of the operon failed to enhance meropenem
      resistance in E. coli JM107 and P. aeruginosa PAO1. This study could prove that
      MexAB-OprM efflux pump can significantly contribute to meropenem resistance in
      hospital isolates of P. aeruginosa where an acquired resistant mechanism is
      absent. Thus, equal importance should be given for diagnosis of intrinsic
      resistance mechanism so as to minimize treatment failure. As meropenem could not
      enhance mexA transcriptions significantly, there might be a possibility that the
      increase in expression of efflux pump genes does not mediated by single
      antibiotic but rather by a combination of antipseudomonal drugs which are used
      during treatments. Early detection of efflux genes will help in selection of
      proper therapeutic options. 

PMID- 26221723
TI  - Oxidative Stress and Digestive Enzyme Activity of Flatfish Larvae in a Changing
      Ocean.
AB  - Until now, it is not known how the antioxidant and digestive enzymatic machinery
      of fish early life stages will change with the combined effects of future ocean
      acidification and warming. Here we show that high pCO2 (~1600 MUatm)
      significantly decreased metabolic rates (up to 27.4 %) of flatfish larvae, Solea
      senegalensis, at both present (18  degrees C) and warmer temperatures (+4 
      degrees C). Moreover, both warming and hypercapnia increased the heat shock
      response and the activity of antioxidant enzymes, namely catalase (CAT) and
      glutathione S-transferase (GST), mainly in post-metamorphic larvae (30 dph). The
      lack of changes in the activity of CAT and GST of pre-metamorphic larvae (10 dph)
      seems to indicate that earlier stages lack a fully-developed antioxidant defense
      system. Nevertheless, the heat shock and antioxidant responses of post
      metamorphic larvae were not enough to avoid the peroxidative damage, which was
      greatly increased under future environmental conditions. Digestive enzymatic
      activity of S. senegalensis larvae was also affected by future predictions.
      Hypercapnic conditions led to a decrease in the activity of digestive enzymes,
      both pancreatic (up to 26.1 % for trypsin and 74.5 % for amylase) and intestinal
      enzymes (up to 36.1 % for alkaline phosphatase) in post-metamorphic larvae.
      Moreover, the impact of ocean acidification and warming on some of these
      physiological and biochemical variables (namely, lower OCR and higher HSP and MDA
      levels) were translated into larvae performance, being significantly correlated
      with decreased larval growth and survival or increased incidence of skeletal
      deformities. The increased vulnerability of flatfish early life stages under
      future ocean conditions is expected to potentially determine recruitment and
      population dynamics in marine ecosystems. 

PMID- 26221724
TI  - Feasibility of a Short-Arm Centrifuge for Mouse Hypergravity Experiments.
AB  - To elucidate the pure impact of microgravity on small mammals despite
      uncontrolled factors that exist in the International Space Station, it is
      necessary to construct a 1 g environment in space. The Japan Aerospace
      Exploration Agency has developed a novel mouse habitat cage unit that can be
      installed in the Cell Biology Experiment Facility in the Kibo module of the
      International Space Station. The Cell Biology Experiment Facility has a short-arm
      centrifuge to produce artificial 1 g gravity in space for mouse experiments.
      However, the gravitational gradient formed inside the rearing cage is larger when
      the radius of gyration is shorter; this may have some impact on mice.
      Accordingly, biological responses to hypergravity induced by a short-arm
      centrifuge were examined and compared with those induced by a long-arm
      centrifuge. Hypergravity induced a significant Fos expression in the central
      nervous system, a suppression of body mass growth, an acute and transient
      reduction in food intake, and impaired vestibulomotor coordination. There was no
      difference in these responses between mice raised in a short-arm centrifuge and
      those in a long-arm centrifuge. These results demonstrate the feasibility of
      using a short-arm centrifuge for mouse experiments. 

PMID- 26221725
TI  - MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy
      Sensitivity in Oesophageal Adenocarcinoma.
AB  - Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths
      worldwide, and the 5-year survival rate for patients diagnosed with the disease
      is approximately 17%. The standard of care for locally advanced disease is
      neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation
      therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail
      to respond to neo-CRT. Therefore, the identification of biomarkers indicative of
      patient response to treatment has significant clinical implications in the
      stratification of patient treatment. Furthermore, understanding the molecular
      mechanisms underpinning tumour response and resistance to neo-CRT will contribute
      towards the identification of novel therapeutic targets for enhancing OAC
      sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein
      expression and play a causal role in cancer development and progression. MiRNAs
      have also been identified as modulators of key cellular pathways associated with
      resistance to CRT. Here, to identify miRNAs associated with resistance to CRT,
      pre-treatment diagnostic biopsy specimens from patients with OAC were analysed
      using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most
      downregulated miRNA in patients who subsequently failed to respond to neo-CRT.
      The role of miR-330 as a potential modulator of tumour response and sensitivity
      to CRT in OAC was further investigated in vitro. Through vector-based
      overexpression the E2F1/p-AKT survival pathway, as previously described, was
      confirmed as a target of miR-330 regulation. However, miR-330-mediated
      alterations to the E2F1/p-AKT pathway were insufficient to significantly alter
      cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast,
      silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to
      clinically relevant doses of radiation. This study highlights the need for
      further investigation into the potential of miR-330-5p as a predictive biomarker
      of patient sensitivity to neo-CRT and as a novel therapeutic target for
      manipulating cellular sensitivity to neo-CRT in patients with OAC. 

PMID- 26221726
TI  - Regulation of Vapor Pressure Deficit by Greenhouse Micro-Fog Systems Improved
      Growth and Productivity of Tomato via Enhancing Photosynthesis during Summer
      Season.
AB  - The role of a proposed micro-fog system in regulating greenhouse environments and
      enhancing tomato (Solanum lycopersicum L.) productivity during summer season was
      studied. Experiments were carried out in a multi-span glass greenhouse, which was
      divided into two identical compartments involving different environments: (1)
      without environment control and (2) with a micro-fog system operating when the
      air vapor pressure deficit (VPD) of greenhouse was higher than 0.5 KPa. The micro
      fog system effectively alleviated heat stress and evaporative demand in the
      greenhouse during summer season. The physiologically favourable environment
      maintained by micro-fog treatment significantly enhanced elongation of leaf and
      stem, which contributed to a substantial elevation of final leaf area and shoot
      biomass. These improvements in physiological and morphological traits resulted in
      around 12.3% increase of marketable tomato yield per plant. Relative growth rate
      (RGR) of micro-fog treatment was also significantly higher than control plants,
      which was mainly determined by the substantial elevation in net assimilation rate
      (NAR), and to a lesser extent caused by leaf area ratio (LAR). Measurement of
      leaf gas exchange parameters also demonstrated that micro-fog treatment
      significantly enhanced leaf photosynthesis capacity. Taken together, manipulation
      of VPD in greenhouses by micro-fog systems effectively enhanced tomato growth and
      productivity via improving photosynthesis during summer season. 

PMID- 26221727
TI  - Domestic Banks in Bangladesh Could Ensure Efficiency by Improving Human Resource
      Management Practices.
AB  - The paper aims to examine the influence of human resource management (HRM)
      practices on bank efficiency using Malmquist index of total factor productivity.
      The model comprises HRM index that represents the quality of HRM practices. The
      results are decomposed into three efficiency scores, namely, technical
      efficiency, pure efficiency, and scale efficiency. In this study, panel data for
      44 banks in Bangladesh are used for the period 2008-2013. This paper reveals that
      foreign banks are ahead in converting the influence of HRM practices into
      efficiency scores (0.946>0.833). On the other hand, domestic banks performed
      better than foreign banks in terms of pure efficiency and scale efficiency. But,
      in terms of technical efficiency, the domestic banks are regressed by 6.7%
      annually whereas foreign banks are progressed with a yearly value of 5.8%. The
      results are robust, because the Mann-Whitney test and Kruskall-Wallis test (non
      parametric tests) also confirm the same results. This study emphasizes HRM
      practices in the banking industry to ensure efficiency in the long-term scenario.
      Domestic banks are suggested to ensure continuous development in HRM practices in
      order to compete with foreign banks. 

PMID- 26221729
TI  - Correction: Molecular Epidemiology of Clostridium difficile Infection in a Large
      Teaching Hospital in Thailand.

PMID- 26221728
TI  - Preclinical Evaluation of a Potential GSH Ester Based PET/SPECT Imaging Probe
      DT(GSHMe)2 to Detect Gamma Glutamyl Transferase Over Expressing Tumors.
AB  - Gamma Glutamyl Transferase (GGT) is an important biomarker in malignant cancers.
      The redox processes ensuing from GGT-mediated metabolism of extracellular GSH are
      implicated in critical aspects of tumor cell biology. Reportedly, Glutathione
      monoethyl ester (GSHMe) is a substrate of GGT, which has been used for its rapid
      transport over glutathione. Exploring GGT to be an important target, a
      homobivalent peptide system, DT(GSHMe)2 was designed to target GGT-over
      expressing tumors for diagnostic purposes. DT(GSHMe)2 was synthesized,
      characterized and preclinically evaluated in vitro using toxicity, cell binding
      assays and time dependent experiments. Stable and defined radiochemistry with
      99mTc and 68Ga was optimized for high radiochemical yield. In vivo
      biodistribution studies were conducted for different time points along with
      scintigraphic studies of radiolabeled DT(GSHMe)2 on xenografted tumor models. For
      further validation, in silico docking studies were performed on GGT (hGGT1,
      P19440). Preclinical in vitro evaluations on cell lines suggested minimal
      toxicity of DT(GSHMe)2 at 100 MUM concentration. Kinetic analysis revealed
      transport of 99mTc-DT(GSHMe)2 occurs via a saturable high-affinity carrier with
      Michaelis constant (Km) of 2.25 MUM and maximal transport rate velocity (Vmax) of
      0.478 MUM/min. Quantitative estimation of GGT expression from western blot
      experiments showed substantial expression with 41.6 +/- 7.07 % IDV for tumor.
      Small animal micro PET (Positron Emission Tomography)/CT(Computed Tomography)
      coregistered images depicted significantly high uptake of DT(GSHMe)2 at the BMG-1
      tumor site. ROI analysis showed high tumor to contra lateral muscle ratio of 9.33
      in PET imaging studies. Avid accumulation of radiotracer was observed at tumor
      versus inflammation site at 2 h post i.v. injection in an Ehrlich Ascites tumor
      (EAT) mice model, showing evident specificity for tumor. We propose DT(GSHMe)2 to
      be an excellent candidate for prognostication and tumor imaging using PET/SPECT. 

PMID- 26221730
TI  - In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A.
AB  - A new DNA aptamer targeting Protein A is presented. The aptamer was selected by
      use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of
      Ligands by EXponential enrichment) is widely applied as an in vitro selection and
      amplification method to generate target-specific aptamers and exists in various
      modified variants. FluMag-SELEX is one of them and is characterized by the use of
      magnetic beads for target immobilization and fluorescently labeled
      oligonucleotides for monitoring the aptamer selection progress. Structural
      investigations and sequence truncation experiments of the selected aptamer for
      Protein A led to the conclusion, that a stem-loop structure at its 5'-end
      including the 5'-primer binding site is essential for aptamer-target binding.
      Extensive interaction analyses between aptamer and Protein A were performed by
      methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based
      binding assays using fluorescence measurements. The binding of the aptamer to its
      target was thus investigated in assays with immobilization of one of the binding
      partners each, and with both binding partners in solution. Affinity constants
      were determined in the low micromolar to submicromolar range, increasing to the
      nanomolar range under the assumption of avidity. Protein A provides more than one
      binding site for the aptamer, which may overlap with the known binding sites for
      immunoglobulins. The aptamer binds specifically to both native and recombinant
      Protein A, but not to other immunoglobulin-binding proteins like Protein G and L.
      Cross specificity to other proteins was not found. The application of the aptamer
      is directed to Protein A detection or affinity purification. Moreover, whole
      cells of Staphylococcus aureus, presenting Protein A on the cell surface, could
      also be bound by the aptamer. 

PMID- 26221731
TI  - A Role for the Mitochondrial Protein Mrpl44 in Maintaining OXPHOS Capacity.
AB  - We identified Mrpl44 in a search for mammalian proteins that contain RNase III
      domains. This protein was previously found in association with the mitochondrial
      ribosome of bovine liver extracts. However, the precise Mrpl44 localization had
      been unclear. Here, we show by immunofluorescence microscopy and subcellular
      fractionation that Mrpl44 is localized to the matrix of the mitochondria. We
      found that it can form multimers, and confirm that it is part of the large
      subunit of the mitochondrial ribosome. By manipulating its expression, we show
      that Mrpl44 may be important for regulating the expression of mtDNA-encoded
      genes. This was at the level of RNA expression and protein translation. This
      ultimately impacted ATP synthesis capability and respiratory capacity of cells.
      These findings indicate that Mrpl44 plays an important role in the regulation of
      the mitochondrial OXPHOS capacity. 

PMID- 26221732
TI  - Comparison Analysis of Dysregulated LncRNA Profile in Mouse Plasma and Liver
      after Hepatic Ischemia/Reperfusion Injury.
AB  - Long noncoding RNAs (LncRNAs) have been believed to be the major transcripts in
      various tissues and organs, and may play important roles in regulation of many
      biological processes. The current study determined the LncRNA profile in mouse
      plasma after liver ischemia/reperfusion injury (IRI) using microarray technology.
      Microarray assays revealed that 64 LncRNAs were upregulated, and 244 LncRNAs were
      downregulated in the plasma of liver IRI mouse. Among these dysregulated plasma
      LncRNAs, 59-61% were intergenic, 22-25% were antisense overlap, 8-12% were sense
      overlap and 6-7% were bidirectional. Ten dysregulated plasma LncRNAs were
      validated by quantitative PCR assays, confirming the accuracy of microarray
      analysis result. Comparison analysis between dysregulated plasma and liver LncRNA
      profile after liver IRI revealed that among the 308 dysregulated plasma LncRNAs,
      245 LncRNAs were present in the liver, but remained unchanged. In contrast, among
      the 98 dysregulated liver LncRNAs after IRI, only 19 were present in the plasma,
      but remained unchanged. LncRNA AK139328 had been previously reported to be
      upregulated in the liver after IRI, and silencing of hepatic AK139328 ameliorated
      liver IRI. Both microarray and RT-PCR analyses failed to detect the presence of
      AK139328 in mouse plasma. In summary, the current study compared the difference
      between dysregulated LncRNA profile in mouse plasma and liver after liver IRI,
      and suggested that a group of dysregulated plasma LncRNAs have the potential of
      becoming novel biomarkers for evaluation of ischemic liver injury. 

PMID- 26221733
TI  - A New Electromagnetic Navigation System for Pedicle Screws Placement: A Human
      Cadaver Study at the Lumbar Spine.
AB  - INTRODUCTION: Technical developments for improving the safety and accuracy of
      pedicle screw placement play an increasingly important role in spine surgery. In
      addition to the standard techniques of free-hand placement and fluoroscopic
      navigation, the rate of complications is reduced by 3D fluoroscopy, cone-beam CT,
      intraoperative CT/MRI, and various other navigation techniques. Another important
      aspect that should be emphasized is the reduction of intraoperative radiation
      exposure for personnel and patient. The aim of this study was to investigate the
      accuracy of a new navigation system for the spine based on an electromagnetic
      field. MATERIAL AND METHOD: Twenty pedicle screws were placed in the lumbar spine
      of human cadavers using EMF navigation. Navigation was based on data from a
      preoperative thin-slice CT scan. The cadavers were positioned on a special field
      generator and the system was matched using a patient tracker on the spinous
      process. Navigation was conducted using especially developed instruments that can
      be tracked in the electromagnetic field. Another thin-slice CT scan was made
      postoperatively to assess the result. The evaluation included the position of the
      screws in the direction of trajectory and any injury to the surrounding cortical
      bone. The results were classified in 5 groups: grade 1: ideal screw position in
      the center of the pedicle with no cortical bone injury; grade 2: acceptable screw
      position, cortical bone injury with cortical penetration <= 2 mm; grade 3:
      cortical bone injury with cortical penetration 2,1-4 mm, grad 4: cortical bone
      injury with cortical penetration 4,1-6 mm, grade 5: cortical bone injury with
      cortical penetration >6 mm. RESULTS: The initial evaluation of the system showed
      good accuracy for the lumbar spine (65% grade 1, 20% grade 2, 15% grade 3, 0%
      grade 4, 0% grade 5). A comparison of the initial results with other navigation
      techniques in literature (CT navigation, 2D fluoroscopic navigation) shows that
      the accuracy of this system is comparable. CONCLUSION: EMF navigation offers a
      high accuracy in Pedicle screw placement with additional advantages compared to
      other techniques. The short set-up time and easy handling of EMF navigation
      should be emphasized. Additional advantages are the absence of intraoperative
      radiation exposure for the operator and surgical team in the current set-up and
      the operator's free mobility without interfering with navigation. Further studies
      with navigation at higher levels of the spine, larger numbers of cases and
      studies with control group are planned.

PMID- 26221734
TI  - The Measurement of Subjective Value and Its Relation to Contingent Valuation and
      Environmental Public Goods.
AB  - Environmental public goods--including national parks, clean air/water, and
      ecosystem services--provide substantial benefits on a global scale. These goods
      have unique characteristics in that they are typically "nonmarket" goods, with
      values from both use and passive use that accrue to a large number of individuals
      both in current and future generations. In this study, we test the hypothesis
      that neural signals in areas correlated with subjective valuations for
      essentially all other previously studied categories of goods (ventromedial
      prefrontal cortex and ventral striatum) also correlate with environmental
      valuations. We use contingent valuation (CV) as our behavioral tool for measuring
      valuations of environmental public goods. CV is a standard stated preference
      approach that presents survey respondents with information on an issue and asks
      questions that help policymakers determine how much citizens are willing to pay
      for a public good or policy. We scanned human subjects while they viewed
      environmental proposals, along with three other classes of goods. The
      presentation of all four classes of goods yielded robust and similar patterns of
      temporally synchronized brain activation within attentional networks. The
      activations associated with the traditional classes of goods replicate previous
      correlations between neural activity in valuation areas and behavioral
      preferences. In contrast, CV-elicited values for environmental proposals did not
      correlate with brain activity at either the individual or population level. For a
      sub-population of participants, CV-elicited values were correlated with activity
      within the dorsomedial prefrontal cortex, a region associated with cognitive
      control and shifting decision strategies. The results show that neural activity
      associated with the subjective valuation of environmental proposals differs
      profoundly from the neural activity associated with previously examined goods and
      preference measures.

PMID- 26221735
TI  - Multiple Convergent Origins of Workerlessness and Inbreeding in the Socially
      Parasitic Ant Genus Myrmoxenus.
AB  - The socially parasitic ant genus Myrmoxenus varies strongly in fundamental life
      history traits, such as queen-worker ratio, the timing of sexual production, and
      mating behavior. Myrmoxenus queens generally take over nests of Temnothorax ants,
      kill the resident queen by throttling, and force the workers to take care of the
      social parasite's brood. Young queens of M. ravouxi and other species produce
      large numbers of workers, which during "slave-raids" pillage host pupae from
      neighboring Temnothorax colonies to increase the workforce in their own nests.
      Other species, such as M. corsicus, have lost caste polyphenism and rear only
      male and female sexual offspring. Using sequences of the genes CO I/CO II and
      wingless we reconstruct the phylogeny of Myrmoxenus and document that the worker
      caste was lost convergently at least three times. Furthermore, mating in the nest
      and inbreeding obviously also evolved in parallel from ancestors whose sexuals
      presumably mated during nuptial flights. Myrmoxenus might thus provide a suitable
      model to investigate caste differentiation and the plasticity of mating behavior
      in Hymenoptera.

PMID- 26221736
TI  - Correction: Determinants and Experiences of Repeat Pregnancy among HIV-Positive
      Kenyan Women--A Mixed-Methods Analysis.

PMID- 26221740
TI  - Clinical Outcomes of Retinal Detachment Surgery following Cytomegalovirus
      Retinitis in Patients on Highly Active Anti-retroviral Therapy for Acquired
      Immune Deficiency Syndrome.
AB  - AIM: The objective of this study is to describe the surgical outcomes of patients
      of HIV on HAART who underwent surgery for CMV retinitis related retinal
      detachment. METHOD AND MATERIALS: A retrospective analysis of the medical records
      of 40 eyes of 35 consecutive HIV positive patients who underwent surgical repair
      for CMV retinitis associated rhegmatogenous retinal detachment between January
      2000 to August 2010 was done. All patients had an adequate follow up of atleast 6
      months. RESULTS: Favourable anatomical outcome was achieved in 78 % of eyes with
      the eyes having a attached retina, clear media and controlled intraocular
      pressure.Favourable functional outcome (vision >3/60) was achieved in 56%.
      CONCLUSION: Though anatomical outcomes have not changed from the pre HAART era
      but there has been an increase in favorable functional outcomes possibly due to
      effects of antiretroviral therapy.

PMID- 26221737
TI  - Time with friends and physical activity as mechanisms linking obesity and
      television viewing among youth.
AB  - BACKGROUND: Though bivariate relationships between childhood obesity, physical
      activity, friendships and television viewing are well documented, empirical
      assessment of the extent to which links between obesity and television may be
      mediated by these factors is scarce. This study examines the possibility that
      time with friends and physical activity are potential mechanisms linking
      overweight/obesity to television viewing in youth. METHODS: Data were drawn from
      children ages 10-18 years old (M = 13.81, SD = 2.55) participating in the 2002
      wave of Child Development Supplement (CDS) to the Panel Study of Income Dynamics
      (PSID) (n = 1,545). Data were collected both directly and via self-report from
      children and their parents. Path analysis was employed to examine a model whereby
      the relationships between youth overweight/obesity and television viewing were
      mediated by time spent with friends and moderate-to-vigorous physical activity
      (MVPA). RESULTS: Overweight/obesity was directly related to less time spent with
      friends, but not to MVPA. Time spent with friends was directly and positively
      related to MVPA, and directly and negatively related to time spent watching
      television without friends. In turn, MVPA was directly and negatively related to
      watching television without friends. There were significant indirect effects of
      both overweight/obesity and time with friends on television viewing through MVPA,
      and of overweight/obesity on MVPA through time with friends. Net of any indirect
      effects, the direct effect of overweight/obesity on television viewing remained.
      The final model fit the data extremely well (chi2 = 5.77, df = 5, p<0.0001, RMSEA
      = 0.01, CFI = 0.99, TLI =0.99). CONCLUSIONS: We found good evidence that the
      positive relationships between time with friends and physical activity are
      important mediators of links between overweight/obesity and television viewing in
      youth. These findings highlight the importance of moving from examinations of
      bivariate relationships between weight status and television viewing to more
      nuanced explanatory models which attempt to identify and unpack the possible
      mechanisms linking them.

PMID- 26221741
TI  - Techniques and applications of skeletal muscle diffusion tensor imaging: A
      review.
AB  - Diffusion tensor imaging (DTI) is increasingly applied to study skeletal muscle
      physiology, anatomy, and pathology. The reason for this growing interest is that
      DTI offers unique, noninvasive, and potentially diagnostically relevant imaging
      readouts of skeletal muscle structure that are difficult or impossible to obtain
      otherwise. DTI has been shown to be feasible within most skeletal muscles. DTI
      parameters are highly sensitive to patient-specific properties such as age, body
      mass index (BMI), and gender, but also to more transient factors such as
      exercise, rest, pressure, temperature, and relative joint position. However, when
      designing a DTI study one should not only be aware of sensitivity to the above
      mentioned factors but also the fact that the DTI parameters are dependent on
      several acquisition parameters such as echo time, b-value, and diffusion mixing
      time. The purpose of this review is to provide an overview of DTI studies
      covering the technical, demographic, and clinical aspects of DTI in skeletal
      muscles. First we will focus on the critical aspects of the acquisition protocol.
      Second, we will cover the reported normal variance in skeletal muscle diffusion
      parameters, and finally we provide an overview of clinical studies and reported
      parameter changes due to several (patho-)physiological conditions.

PMID- 26221742
TI  - The ubiquitin proteasome system as a potential therapeutic target for treatment
      of neurodegenerative diseases.
AB  - Impairment of "protein quality control" in neurons is associated with
      etiopathogenesis of neurodegenerative diseases. The worn-out products of cell
      metabolism should be safely eliminated via the proteasome, autophago-lysosome and
      exocytosis. Insufficient activity of these degradation mechanisms within neurons
      leads to the accumulation of toxic protein oligomers, which represent a starting
      material for development of neurodegenerative proteinopathy. The spectrum of CNS
      linked proteinopathies is particularly broad and includes Alzheimer's disease
      (AD), Parkinson's disease (PD), Lewy body dementia, Pick disease, Frontotemporal
      dementia, Huntington disease, Amyotrophic lateral sclerosis and many others.
      Although the primary events in etiopathogenesis of sporadic forms of these
      diseases are still unknown, it is clear that aging, in connection with decreased
      activity of ubiquitin proteasome system, is the most significant risk factor. In
      this review we discuss the pathogenic role and intracellular fate of the
      candidate molecules associated with onset and progression of AD and PD, the
      protein tau and alpha-synuclein in context with the function of ubiquitin
      proteasome system. We also discuss the possibility whether or not the strategies
      focused to re-establishment of neuroproteostasis via accelerated clearance of
      damaged proteins in proteasome could be a promising therapeutic approach for
      treatment of major neurodegenerative diseases.

PMID- 26221743
TI  - Hypothermia mitigates neurochemical alterations in rat's cerebral cortex during
      status epilepticus induced by pilocarpine.
AB  - Status epilepticus (SE) is a prolonged seizure activity associated with mortality
      and morbidity. SE is characterized by changes in neurotransmitter systems and
      oxidative stress that facilitate cellular damage. These alterations represent the
      neurochemical mechanisms underlying the initiation and progression of seizure
      activity and co-existing morbidity. In the present study, amino acid levels
      (glutamine, glutamate, GABA, aspartate, glycine and taurine) and oxidative stress
      parameters malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide NO)
      were determined in the cerebral cortex during SE induced by pilocarpine in rats.
      The study has also evaluated the effects of hypothermia, as a physical non
      invasive tool, on neurotransmitters and oxidative stress alterations. The results
      obtained revealed that there are significant increases in glutamate, GABA,
      glycine and taurine and NO in the cortex of pilocarpinzed rats. Hypothermia
      pretreatment mitigated most of the alterations induced by pilocarpine and
      significantly decreased GABA concentration. These findings emphasize the
      involvement of extrahippocampal amino acid neurotransmitters in pilocarpine
      induced SE and the ameliorative role played by hypothermia.

PMID- 26221744
TI  - Acidotropic properties of synthetic hexahydropyridoindole antioxidants.
AB  - In acidic intracellular organelles, sequestration via a proton-trapping mechanism
      is observed for many amine-containing drugs. It may be related to several adverse
      effects of a drug, yet accumulation of amines bearing antioxidant functionality
      may provide efficient protection of these compartments. In the present study, a
      possible proton-trapping mechanism of the novel antioxidant reference stobadine
      (STO) and its selected derivatives was investigated also with regard to their
      antioxidant properties, using BV-2 microglia. Unlike its 2-ethoxycarbonyl-8
      methoxy derivative EC-STO (pKa1 4.95, pKa2 -3.58), STO, bearing weakly basic
      piperidine moiety (pKa2 9.03), induced vacuolar response in the cells. EC-STO,
      compared to STO, failed to provide better protection against oxidative damage
      induced by tert-butyl hydroperoxide (BHP), and that in spite of its predicted
      improved bioavailability and antioxidant properties. However, disruption of the
      lysosomal proton gradient abolished the efficacy of STO in suppressing oxidants
      generation and injury of the cells. NT-STO, the 6-nitro derivative of stobadine,
      lacking antiradical efficacy, showed a lower effect in protecting the cells
      against BHP. In conclusion, our study suggests that weakly basic
      hexahydropyridoindoles may act as lysosomotropic compounds. Furthermore, their
      weakly basic characteristics may contribute to their improved efficacy in
      suppressing peroxidative processes within lysosomes, and thus possibly combating
      ageing-related pathologies.

PMID- 26221745
TI  - Lymph node mapping using quantum dot-labeled polymersomes.
AB  - The present study was designed to investigate whether poly-ion complex hollow
      vesicles (polymersomes), based on chemically-modified chitosan, are appropriate
      for lymph node mapping in the context of their application in the development of
      theranostic nanosized drug delivery systems (nano-DDS). The experiments were
      performed on Balb/c nude mice (colon cancer-grafted). The mice were subjected to
      anesthesia and quantum dot (QD(705))-labeled polymersomes (d-120 nm) were
      injected intravenously via the tail vein. The optical imaging was carried out on
      Maestro EX Imaging System (excitation filter: 435-480 nm; emission filter: 700
      nm). A strong fluorescent signal, corresponding to QD(705) fluorescence, was
      detected in the lymph nodes, as well as in the tumor. A very weak fluorescent
      signal was found in the liver area. The half-life of QD(705)-labelled
      polymersomes was 6 +/- 2 hours in the bloodstream and 11 +/- 3 hours in the lymph
      nodes. The data suggest that polymersomes are very promising carriers for lymph
      node mapping using QD as a contrast agent. They are useful matrix for development
      of nano-formulations with theranostic capabilities.

PMID- 26221746
TI  - Too little O2 Too much gain.

PMID- 26221747
TI  - Rehabilitation of a Bilateral Maxillectomy Patient with a Free Fibula
      Osteocutaneous Flap and with an Implant-Retained Obturator: A Clinical Report.
AB  - A 47-year-old man underwent surgical resection and reconstruction with a fibula
      osteocutaneous flap. After the surgery, a surgical obturator was placed and
      adjusted. After flap healing, a conventional obturator was fabricated with
      polymethyl methacrylate resin and retained by the anatomical undercuts around the
      reconstructed fibula bone flap and the posterior part of the defect. As the
      defect shape changed with time, a second conventional obturator was fabricated
      and fitted. No further recurrence of myoepithelioma was observed for 2 years, and
      the patient was satisfied with the obturator during mastication and speech;
      however, despite having no major complaints, the patient found it difficult to
      chew on the right side, and the obturator was displaced slightly downward when
      the mouth was opened wide and shifted when chewing hard and sticky food. Thus, an
      implant-retained obturator was suggested to provide better retention and
      stability. Four dental implants were therefore placed into the fibula bone,
      although one did not osseointegrate because either primary stability was
      insufficient or overload was affected in the nonloaded implant environment and
      was replaced. After fitting custom abutments with a magnet, an implant-retained
      obturator was placed, and the patient was satisfied with the outcome. During 3
      years of follow-up, no issues were noted with the implant bodies, abutments,
      obturator, or reconstructed site. The conventional obturator was displaced
      slightly downward when the patient opened his mouth wide, and it shifted when
      chewing hard and sticky food because there was limited fibula bone at the
      reconstruction site and more available posteriorly. For better retention and
      stability, the implant-retained obturator was fabricated with a custom abutment
      and magnetic retention. The patient was satisfied with the results, as improved
      implant retention increased the stability of the prosthesis. This clinical report
      describes the rehabilitation of a bilateral maxillectomy patient with a free
      fibula osteocutaneous flap and an implant-retained obturator. The patient's oral
      functions were improved when the prosthesis was stabilized by means of dental
      implants and custom abutments. 

PMID- 26221748
TI  - 1- and 2-photon ionization for online FAIMS-FTMS coupling allows new insights
      into the constitution of crude oils.
AB  - Photoionization techniques (APPI and APLI) are important for the mass
      spectrometric analysis of crude oils, given the mainly unpolar character of the
      sample. Ultrahigh resolving Fourier Transform mass spectrometry (FTMS) allows to
      distinguish between most isobaric compounds as well as to unambiguously determine
      the elemental compositions of the detected ions. Nevertheless, the complexity of
      crude oil makes its thorough analysis a difficult task. Besides discriminating
      effects that can be avoided and depth of information that can be gained by
      simplification of the sample prior to the MS analysis the presence of numerous
      isomeric compounds limits the amount of information that can be gained by mass
      spectrometry alone. Ion mobility spectrometry (IMS) has been shown to be a
      valuable tool for isomer separation and has also been employed for the analysis
      of crude oils using IMS-TOF MS. The application of an online FAIMS-FTMS coupling
      after photoionization for the analysis of crude oils is shown. With this setup
      the complementarity of data obtained from both APPI and APLI ionization is
      demonstrated. Online separation and individual detection of different hydrocarbon
      isomers is achieved. 

PMID- 26221749
TI  - Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody.
AB  - BACKGROUND: The calcium-binding 2EF-hand protein Phl p 7 from timothy grass
      pollen is a highly cross-reactive pollen pan-allergen that can induce severe
      clinical symptoms in allergic patients. Recently, a human monoclonal Phl p 7
      specific IgG4 antibody (mAb102.1F10) was isolated from a patient who had received
      grass pollen-specific immunotherapy (SIT). METHODS: We studied epitope
      specificity, cross-reactivity, affinity and cross-protection of mAb102.1F10
      towards homologous calcium-binding pollen allergens. Sequence comparisons and
      molecular modelling studies were performed with ClustalW and SPADE, respectively.
      Surface plasmon resonance measurements were made with purified recombinant
      allergens. Binding and cross-reactivity of patients' IgE and mAb102.1F10 to
      calcium-binding allergens and peptides thereof were studied with quantitative
      RAST-based methods, in ELISA, basophil activation and IgE-facilitated allergen
      presentation experiments. RESULTS: Allergens from timothy grass (Phl p 7), alder
      (Aln g 4), birch (Bet v 4), turnip rape (Bra r 1), lamb's quarter (Che a 3) and
      olive (Ole e 3, Ole e 8) showed high sequence similarity and cross-reacted with
      allergic patients' IgE. mAb102.1F10 bound the C-terminal portion of Phl p 7 in a
      calcium-dependent manner. It cross-reacted with high affinity with Ole e 3,
      whereas binding and affinity to the other allergens were low. mAb102.1F10 showed
      limited cross-inhibition of patients' IgE binding and basophil activation.
      Sequence comparison and surface exposure calculations identified three amino
      acids likely to be responsible for limited cross-reactivity. CONCLUSIONS: Our
      results demonstrate that a small number of amino acid differences among cross
      reactive allergens can reduce the affinity of binding by a SIT-induced IgG and
      thus limit cross-protection.

PMID- 26221750
TI  - National trends in acute kidney injury requiring dialysis in England between 1998
      and 2013.
AB  - Acute kidney injury (AKI) severe enough to require dialysis is increasing and
      associated with high mortality, yet robust information about temporal
      epidemiology of AKI requiring dialysis in England is lacking. In this
      retrospective observational study of the Hospital Episode Statistics (HES) data
      set covering the entire English National Health Service, we identified all
      patients with a diagnosis of AKI requiring dialysis between 1998 and 2013. This
      incidence increased from 774 cases (15.9 per million people) in 1998-1999 to
      11,164 cases (208.7 per million people) in 2012-2013. The unadjusted in-hospital
      case-fatality was 30.3% in 1998-2003 and 30.2% in 2003-2008, but significantly
      increased to 41.1% in 2008-2013. Compared with 2003-2008, the multivariable
      adjusted odds ratio for death was higher in 1998-2003 at 1.20 (95% CI: 1.10-1.30)
      and in 2008-2013 at 1.13 (1.07-1.18). Charlson comorbidity scores of more than
      five (odds ratio 2.35; 95% CI: 2.20-2.51) and emergency admissions (2.46 (2.32
      2.61) had higher odds for death. The odds for death decreased in patients over 85
      years from 4.83 (3.04-7.67) in 1998-2003 to 2.19 (1.99-2.41) in 2008-2013. AKI in
      secondary diagnosis and in other diagnoses codes had higher odds for death
      compared with AKI in primary diagnosis code in all three periods. Thus, the
      incidence of AKI requiring dialysis has increased progressively over 15 years in
      England. Improvement in case-fatality in 2003-2008 has not been sustained in the
      last 5 years. 

PMID- 26221751
TI  - A revised strategy for monitoring BKV-specific cellular immunity in kidney
      transplant patients.
AB  - Reactivation of Polyomavirus BKV is a severe complication in kidney transplant
      patients. Current treatment requires close monitoring, and modification of
      immunosuppressive drugs. As an important additional tool, the monitoring of BKV
      immunity has been based on detection of cytokine-secreting T cells upon BKV
      antigen challenge. However, low frequent BKV-specific T cells are often barely
      detectable and their roles in BKV clearance remain unclear. Here, we analyzed the
      effects of immunosuppressive agents on BKV-specific T cells in vitro. Significant
      reductions in expression of several markers, and reduced killing functions upon
      treatment with calcineurin but not mTOR inhibitors were detected. However,
      effects of these drugs on expression of surface markers and GranzymeB were
      substantially less striking than effects on cytokine expression. Consequently, we
      applied a novel detection strategy for BKV-specific T cells in immunosuppressed
      kidney transplant patients using these more robust markers, and showed
      significantly improved sensitivity compared with the conventional IFNgamma-based
      method. Using this strategy and 17-color flow cytometry, we found BKV-specific
      helper and cytolytic CD4+ T-cell subsets that differed in their memory phenotype,
      which corresponded with BKV clearance in kidney transplant patients. Thus, our
      results offer an improved detection strategy for BKV-specific T cells in kidney
      transplant patients, and shed light on the contributions of these cells to BKV
      clearance.

PMID- 26221752
TI  - A systematic analysis of worldwide population-based data on the global burden of
      chronic kidney disease in 2010.
AB  - Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease,
      cardiovascular disease, and premature death. Here we estimated the global
      prevalence and absolute burden of CKD in 2010 by pooling data from population
      based studies. We searched MEDLINE (January 1990 to December 2014), International
      Society of Nephrology Global Outreach Program-funded projects, and bibliographies
      of retrieved articles and selected 33 studies reporting gender- and age-specific
      prevalence of CKD in representative population samples. The age-standardized
      global prevalence of CKD stages 1-5 in adults aged 20 and older was 10.4% in men
      (95% confidence interval 9.3-11.9%) and 11.8% in women (11.2-12.6%). This
      consisted of 8.6% in men (7.3-9.8%) and 9.6% in women (7.7-11.1%) in high-income
      countries, and 10.6% in men (9.4-13.1%) and 12.5% in women (11.8-14.0%) in low-
      and middle-income countries. The total number of adults with CKD was 225.7
      million (205.7-257.4 million) men and 271.8 million (258.0-293.7 million) women.
      This consisted of 48.3 million (42.3-53.3 million) men and 61.7 million (50.4
      69.9 million) women in high-income countries, and 177.4 million (159.2-215.9
      million) men and 210.1 million (200.8-231.7 million) women in low- and middle
      income countries. Thus, CKD is an important global-health challenge, especially
      in low- and middle-income countries. National and international efforts for
      prevention, detection, and treatment of CKD are needed to reduce its morbidity
      and mortality worldwide. 

PMID- 26221753
TI  - An extended mini-complement factor H molecule ameliorates experimental C3
      glomerulopathy.
AB  - Abnormal regulation of the complement alternative pathway is associated with C3
      glomerulopathy. Complement factor H is the main plasma regulator of the
      alternative pathway and consists of 20 short consensus repeat (SCR) domains.
      Although recombinant full-length factor H represents a logical treatment for C3
      glomerulopathy, its production has proved challenging. We and others have
      designed recombinant mini-factor H proteins in which 'non-essential' SCR domains
      have been removed. Here, we report the in vitro and in vivo effects of a mini
      complement factor H protein, FH1-5^18-20, using the unique factor H-deficient
      (Cfh-/-) mouse model of C3 glomerulopathy. FH1-5^18-20 is comprised of the key
      complement regulatory domains (SCRs 1-5) linked to the surface recognition
      domains (SCRs 18-20). Intraperitoneal injection of FH1-5^18-20 in Cfh-/- mice
      reduced abnormal glomerular C3 deposition, similar to full-length factor H.
      Systemic effects on plasma alternative pathway control were comparatively modest,
      in association with a short half-life. Thus, FH1-5^18-20 is a potential
      therapeutic agent for C3 glomerulopathy and other renal conditions with
      alternative pathway-mediated tissue injury.

PMID- 26221754
TI  - Comorbidity as a driver of adverse outcomes in people with chronic kidney
      disease.
AB  - Chronic kidney disease (CKD) is associated with poor outcomes, perhaps due to a
      high burden of comorbidity. Most studies of CKD populations focus on concordant
      comorbidities, which cause CKD (such as hypertension and diabetes) or often
      accompany CKD (such as heart failure or coronary disease). Less is known about
      the burden of mental health conditions and discordant conditions (those not
      concordant but still clinically relevant, like dementia or cancer). Here we did a
      retrospective population-based cohort study of 530,771 adults with CKD residing
      in Alberta, Canada between 2003 and 2011. Validated algorithms were applied to
      data from the provincial health ministry to assess the presence/absence of 29
      chronic comorbidities. Linkage between comorbidity burden and adverse clinical
      outcomes (mortality, hospitalization or myocardial infarction) was examined over
      median follow-up of 48 months. Comorbidities were classified into three
      categories: concordant, mental health/chronic pain, and discordant. The median
      number of comorbidities was 1 (range 0-15) but a substantial proportion of
      participants had 3 and more, or 5 and more comorbidities (25 and 7%,
      respectively). Concordant comorbidities were associated with excess risk of
      hospitalization, but so were discordant comorbidities and mental health
      conditions. Thus, discordant comorbidities and mental health conditions as well
      as concordant comorbidities are important independent drivers of the adverse
      outcomes associated with CKD.

PMID- 26221755
TI  - Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.
AB  - C3 glomerulonephritis is a clinicopathologic entity defined by the presence of
      isolated or dominant deposits of C3 on immunofluorescence. To explore the effect
      of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients
      in whom a complete registry of treatments was available over a median follow-up
      of 47 months. Twenty patients had not received immunosuppressive treatments. In
      the remaining 40 patients, 22 had been treated with corticosteroids plus
      mycophenolate mofetil while 18 were treated with other immunosuppressive regimens
      (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of
      patients developing end-stage renal disease was significantly lower among treated
      compared with untreated patients (3 vs. 7 patients, respectively). No patient in
      the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor
      developed end-stage renal disease, as compared with 7 (significant) and 3 (not
      significant), respectively, in patients treated with other immunosuppressive
      regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients
      achieving clinical remission (86, 50, and 25%) were significantly higher in
      patients treated with corticosteroids plus mycophenolate mofetil as compared with
      patients treated with other immunosuppressive regimens and untreated patients,
      respectively. Thus, immunosuppressive treatments, particularly corticosteroids
      plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis. 

PMID- 26221756
TI  - The Smad3/Smad4/CDK9 complex promotes renal fibrosis in mice with unilateral
      ureteral obstruction.
AB  - Transforming growth factor-beta1 (TGF-beta1)/Smad signaling has a central role in
      the pathogenesis of renal fibrosis. Smad3 and Smad4 are pro-fibrotic, while Smad2
      is anti-fibrotic. However, these Smads form heterogeneous complexes, the
      functions of which are poorly understood. Here we studied Smad complex function
      in renal fibrosis using the mouse model of unilateral ureteric obstruction. Mice
      heterozygous for Smad3/4 (Smad3/4+/-) exhibited substantial protection from renal
      fibrosis through day 7 of obstruction, whereas Smad2/3+/- and Smad2/4+/- mice
      showed only modest protection. Formation of Smad3/Smad4/CDK9 complexes was an
      early event following obstruction in wild-type mice, which involved nuclear
      phosphorylation of the linker regions of Smad3. Significantly, Smad3 or Smad4
      deficiency decreased the formation of Smad4/CDK9 or Smad3/CDK9 complex, Smad3
      linker phosphorylation, and fibrosis but at different degrees. In vitro, TGF
      beta1 stimulation of collagen I promoter activity involved formation of
      Smad3/Smad4/CDK9 complexes, and overexpression of each component gave additive
      increases in collagen promoter activity. Co-administration of a CDK9 inhibitor
      and Smad3-specific inhibition achieved better protection from TGF-beta1-induced
      fibrotic response in vitro and renal interstitial fibrosis in vivo. Thus
      formation of Smad3/Smad4/CDK9 complex drives renal fibrosis during ureteral
      obstruction. Formation of this complex represents a novel target for antifibrotic
      therapies.

PMID- 26221758
TI  - [Analysis of Fit of the Ascension(r) PyroCarbon PIP Total Joint Component Heads].
AB  - BACKGROUND: The Ascension pyroCarbon proximal interphalangeal (PIP) total joint
      is available in 4 different sizes, and ideally, the prosthesis head will be flush
      with the bone. Fit of the Ascension pyrocarbon PIP joint prosthesis has not yet
      been investigated. MATERIALS AND METHODS: The components of the Ascension
      pyrocarbon PIP total joint were inserted in 287 phalanges of human cadaver
      specimens. The distances from the edge of the component head to the edge of the
      bone were electronically measured radially, ulnarly, dorsally and palmarly on
      radiographs in posterior-anterior and lateral views. RESULTS: Only one finger had
      a precise fit of the heads of both, the proximal and corresponding distal
      component in relation to the bone. Only in 17 (5 proximal, 12 distal) prosthesis
      components the head did the bone fit on all sides. Overall, the proximal
      component head tends to be too large, while the distal component head tends to be
      too small. CONCLUSION: With occasional exceptions, the proximal and distal
      component heads of the Ascension pyrocarbon PIP total joint do not accomodate the
      dimensions of finger phalanges.

PMID- 26221757
TI  - Key role of the kidney in the regulation of fibroblast growth factor 23.
AB  - High circulating levels of fibroblast growth factor 23 (FGF23) have been
      demonstrated in kidney failure, but mechanisms of this are not well understood.
      Here we examined the impact of the kidney on the early regulation of intact FGF23
      in acute uremia as induced by bilateral or unilateral nephrectomy (BNX and UNX,
      respectively) in the rat. BNX induced a significant increase in plasma intact
      FGF23 levels from 112 to 267 pg/ml within 15 min, which remained stable
      thereafter. UNX generated intact FGF23 levels between that seen in BNX and sham
      operated rats. The intact to C-terminal FGF23 ratio was significantly increased
      in BNX rats. The rapid rise in FGF23 after BNX was independent of parathyroid
      hormone or FGF receptor signaling. No evidence of early stimulation of FGF23 gene
      expression in the bone was found. Furthermore, acute severe hyperphosphatemia or
      hypercalcemia had no impact on intact FGF23 levels in normal and BNX rats. The
      half-life of exogenous recombinant human FGF23 was significantly prolonged from
      4.4 to 11.8 min in BNX rats. Measurements of plasma FGF23 in the renal artery and
      renal vein demonstrated a significant renal extraction. Thus the kidney is
      important in FGF23 homeostasis by regulation of its plasma level and metabolism.

PMID- 26221759
TI  - How to synthesize pure Li2-xFeSi1-xPxO4/C (x = 0.03-0.15) easily from low-cost
      Fe(3+) as cathode materials for Li-ion batteries.
AB  - Li2FeSiO4 is a low-cost, environmentally friendly electrode material with high
      theoretical capacity. However, obtaining pure-phase Li2FeSiO4 on a large scale is
      difficult. In this study, pure Li2-xFeSi1-xPxO4/C is prepared easily by using the
      low cost compound Fe(NO3)3.9H2O, with the help of citric acid and appropriate
      ratios of NH4H2PO4 (x = 0.03-0.15). The possible mechanism of the system with
      NH4H2PO4 to synthesize Li2-xFeSi1-xPxO4/C is that there is a catalysis process in
      the system, which helps to produce H2, providing a reducing environment in every
      particle of the reactants guaranteeing a complete change from Fe(3+) to Fe(2+).
      The produced H2 is verified by the gas chromatography of the collected gas
      produced in the calcination process. The ratios of NH4H2PO4 in this system could
      adjust the valence of element Fe in the products. Without NH4H2PO4, an Fe2O3
      impurity is formed accompanying the Li2FeSiO4. With the addition of 1 at%
      NH4H2PO4, the Li4SiO4 impurity accords with the objective Li2-xFeSi1-xPxO4/C.
      Also, Fe with zero-valence could be found as an impurity with the addition of 20
      at% NH4H2PO4 due to overreduction in the system. The synthesized pure Li2-xFeSi1
      xPxO4/C (x = 0.03) displayed the highest discharge capacity of 179 mA h g(-1) in
      the first cycle, the best discharge capacity retention and the most reliable
      redox reversibility of the coulombic efficiency (approximately 100%), compared
      with the synthesized materials with Fe2O3 or Li4SiO4 impurities. 

PMID- 26221760
TI  - What if cell culture media do not mimic in vivo redox settings?
AB  - Here, I address the topic of suitability for redox research of common settings in
      cell cultures. This is done through the prism of in vitro anticancer effects of
      vitamin C. Cell culture media show lower concentrations of iron and a higher
      level of oxygen compared to interstitial fluid. Such a setup promotes ascorbate
      mediated production and accumulation of hydrogen peroxide, which efficiently
      kills a variety of cancer cell lines. However, the anticancer effects are
      annihilated if the iron level is corrected to mimic in vivo concentrations. It
      appears that the potential benefits of application of vitamin C in cancer
      treatment have been significantly overestimated. This might be true for other pro
      oxidative agents as well, such as some (poly)phenols. We urgently need to
      establish medium formula and culture maintenance settings that are optimal for
      redox research. 

PMID- 26221761
TI  - Internalization of Tissue Factor-Rich Microvesicles by Platelets Occurs
      Independently of GPIIb-IIIa, and Involves CD36 Receptor, Serotonin Transporter
      and Cytoskeletal Assembly.
AB  - Platelets are important in hemostasis, but also detect particles and pathogens in
      the circulation. Phagocytic and endocytic activities of platelets are widely
      recognized; however, receptors and mechanisms involved remain poorly understood.
      We previously demonstrated that platelets internalize and store phospholipid
      microvesicles enriched in human tissue factor (TF+MVs) and that platelet
      associated TF enhances thrombus formation at sites of vascular damage. Here, we
      investigate the mechanisms implied in the interactions of TF+MVs with platelets
      and the effects of specific inhibitory strategies. Aggregometry and electron
      microscopy were used to assess platelet activation and TF+MVs uptake.
      Cytoskeletal assembly and activation of phosphoinositide 3-kinase (PI3K) and RhoA
      were analyzed by western blot and ELISA. Exposure of platelets to TF+MVs caused
      reversible platelet aggregation, actin polymerization and association of
      contractile proteins to the cytoskeleton being maximal at 1 min. The same
      kinetics were observed for activation of PI3K and translocation of RhoA to the
      cytoskeleton. Inhibitory strategies to block glycoprotein IIb-IIIa (GPIIb-IIIa),
      scavenger receptor CD36, serotonin transporter (SERT) and PI3K, fully prevented
      platelet aggregation by TF+MVs. Ultrastructural techniques revealed that uptake
      of TF+MVs was efficiently prevented by anti-CD36 and SERT inhibitor, but only
      moderately interfered by GPIIb-IIIa blockade. We conclude that internalization of
      TF+MVs by platelets occurs independently of receptors related to their main
      hemostatic function (GPIIb-IIIa), involves the scavenger receptor CD36, SERT and
      engages PI3-Kinase activation and cytoskeletal assembly. CD36 and SERT appear as
      potential therapeutic targets to interfere with the association of TF+MVs with
      platelets and possibly downregulate their prothrombotic phenotype.

PMID- 26221762
TI  - Upscaling Point Velocity Measurements to Characterize a Glacial Outwash Aquifer.
AB  - Small-scale point velocity probe (PVP)-derived velocities were compared to
      conventional large-scale velocity estimates from Darcy calculations and tracer
      tests, and the possibility of upscaling PVP data to match the other velocity
      estimates was evaluated. Hydraulic conductivity was estimated from grain-size
      data derived from cores, and single-well response testing or slug tests of onsite
      wells. Horizontal hydraulic gradients were calculated using 3-point estimators
      from all of the wells within an extensive monitoring network, as well as by
      representing the water table as a single best fit plane through the entire
      network. Velocities determined from PVP testing were generally consistent in
      magnitude with those from depth specific data collected from multilevel
      monitoring locations in the tracer test, and similar in horizontal flow direction
      to the average hydraulic gradient. However, scaling up velocity estimates based
      on PVP measurements for comparison with site-wide Darcy-based velocities revealed
      issues that challenge the use of Darcy calculations as a generally applicable
      standard for comparison. The Darcy calculations were shown to underestimate the
      groundwater velocities determined both by the PVPs and large-scale tracer
      testing, in a depth-specific sense and as a site-wide average. Some of this
      discrepancy is attributable to the selective placement of the PVPs in the
      aquifer. Nevertheless, this result has important implications for the design of
      in situ treatment systems. It is concluded that Darcy estimations of velocity
      should be supplemented with independent assessments for these kinds of
      applications.

PMID- 26221765
TI  - Full-length genome analysis of canine coronavirus type I.
AB  - Canine coronavirus types I (CCoV-I) and II (CCoV-II) are usually responsible for
      mild enteritis in dogs. While the CCoV-II genome has been completely sequenced,
      to date there are no complete genomic sequence data available publicly for CCoV
      I. Thus, the aim of the present study was to analyze the full-length genome of a
      CCoV-I prototype strain that had been recovered from a dog with diarrhea in
      Italy. CCoV-I strain 23/03 has a genome of 30,000 nucleotides, excluding the 3'
      poly(A) tail, displaying the typical Alphacoronavirus-1 organization and the
      highest genetic relatedness to CCoV-II. However, two distinct features were
      observed in the CCoV-I genome: (i) the presence of an additional ORF between the
      spike (S) protein gene and ORF3a; (ii) the diversity of the S protein, which is
      more closely related to that of feline coronavirus type I and presents a furin
      cleavage site. The present study may contribute to a better understanding of the
      Alphacoronavirus-1 evolutionary pattern and may be paradigmatic of how
      coronaviruses evolve through gene losses, acquisition and exchanges among
      different members. 

PMID- 26221764
TI  - The therapeutic effect of death: Newcastle disease virus and its antitumor
      potential.
AB  - Programmed cell death is essential to survival of multicellular organisms.
      Previously restricted to apoptosis, the concept of programmed cell death is now
      extended to other mechanisms, as programmed necrosis or necroptosis, autophagic
      cell death, pyroptosis and parthanatos, among others. Viruses have evolved to
      manipulate and take control over the programmed cell death response, and the
      infected cell attempts to neutralize viral infections displaying different stress
      signals and defensive pathways before taking the critical decision of self
      destruction. Learning from viruses and their interplay with the host may help us
      to better understand the complexity of the self-defense death response that when
      altered might cause disorders as important as cancer. In addition, as the fields
      of immunotherapy and oncolytic viruses advance as promising novel cancer
      therapies, the programmed cell death response reemerges as a key point for the
      success of both therapeutic approaches. In this review we summarize the research
      of the multimodal cell death response induced by Newcastle disease viruses (NDV),
      considered nowadays a promising viral oncolytic therapeutic, and how the
      manipulation of the host programmed cell death response can enhance the NDV
      antitumor capacity. 

PMID- 26221766
TI  - Binding chicken Anx2 is beneficial for infection with infectious bursal disease
      virus.
AB  - Infectious bursal disease virus (IBDV) causes a highly contagious disease in
      young chickens and leads to significant economic loss in the poultry industry.
      The identification of host cellular molecules that bind to IBDV will improve the
      understanding of the underlying pathogenic mechanisms. In this study, using a
      virus overlay protein-binding assay (VOPBA) and mass spectrometry (MS) analysis,
      IBDV was found to bind chicken Anx2, a membrane protein fraction from DF-1 cells.
      Its interactions were further confirmed by an overlay assay. The results of an
      immunofluorescence assay and flow cytometry showed that Anx2 could be expressed
      and colocalized with IBDV on the surface of infected cells. Moreover, either the
      soluble recombinant Anx2 or an anti-Anx2 antibody could inhibit IBDV binding to
      and infection of DF-1 cells in a dose-dependent manner. The knockdown of Anx2 of
      DF-1 cells by small interfering RNA clearly reduced the subsequent virus yield,
      and overexpression of Anx2 was capable of enhancing the virus yield. These
      results indicate, for the first time, that binding to Anx2 is beneficial for IBDV
      infection. 

PMID- 26221767
TI  - Attachment representation modulates oxytocin effects on the processing of own
      child faces in fathers.
AB  - Oxytocin (OT) plays a crucial role in parental-infant bonding and attachment.
      Recent functional imaging studies reveal specific attachment and reward related
      brain regions in individuals or within the parent-child dyad. However, the time
      course and functional stage of modulatory effects of OT on attachment-related
      processing, especially in fathers, are poorly understood. To elucidate the
      functional and neural mechanisms underlying the role of OT in paternal-child
      attachment, we performed an event-related potential study in 24 healthy fathers
      who received intranasal OT in a double-blind, placebo-controlled, within-subject
      experimental design. Participants passively viewed pictures of their own child
      (oC), a familiar (fC) and an unfamiliar child (ufC) while event-related
      potentials were recorded. Familiarity of the child's face modulated a broad
      negativity at occipital and temporo-parietal electrodes within a time window of
      300-400ms, presumably reflecting a modulation of the N250 and N300 ERP
      components. The oC condition elicited a more negative potential compared to the
      other familiarity conditions suggesting different activation of perceptual memory
      representations and assignment of emotional valence. Most importantly, this
      familiarity effect was only observed under placebo (PL) and was abolished under
      OT, in particular at left temporo-parietal electrodes. This OT induced
      attenuation of ERP responses was related to habitual attachment representations
      in fathers. In summary, our results demonstrate an OT-specific effect at later
      stages of attachment-related face processing presumably reflecting both
      activation of perceptual memory representations and assignment of emotional
      value. 

PMID- 26221763
TI  - The emerging role of long non-coding RNAs in HIV infection.
AB  - The discovery of long non-coding RNAs (lncRNAs) and the elucidation of the
      mechanisms by which they affect different disease states are providing
      researchers with a better understanding of a wide array of disease pathways.
      Moreover, lncRNAs are presenting themselves as both unique diagnostic biomarkers
      as well as novel targets against which to develop new therapeutics. Here we will
      explore the intricate network of non-coding RNAs associated with infection by the
      human immunodeficiency virus (HIV). Non-coding RNAs derived from both the human
      host as well as those from HIV itself are emerging as important regulatory
      elements. We discuss here the various mechanisms through which both small and
      long non-coding RNAs impact viral replication, pathogenesis and disease
      progression. Given the lack of an effective vaccine or cure for HIV and the scale
      of the current pandemic, a deeper understanding of the complex interplay between
      non-coding RNAs and HIV will support the development of innovative strategies for
      the treatment of HIV/acquired immunodeficiency disease (AIDS). 

PMID- 26221768
TI  - Inhibition of Human Pancreatic Cancer Cell Proliferation by Devil's Club
      Oplopanax horridus and Its Polyacetylene Bioactive Compound.
AB  - Devil's club Oplopanax horridus (DC) is a close relative of ginseng; its inner
      root and stem bark extract showed antiproliferation activity on human leukemia,
      ovarian, breast and colon cancer cells. We study here the effects of DC 70%
      ethanol extract alone, or in combination with cisplatin, gemcitabine, and
      paclitaxel on pancreatic endocrine HP62 and pancreatic ductal carcinoma PANC-1
      and BxPC-3 cells. Antiproliferation activity assay, cell cycle analysis by flow
      cytometry, apoptosis-related markers by antibody array, and RT-PCR assay were
      used for this study. DC extract inhibited proliferation of HP62 with IC50 (50%
      inhibition concentration) at 0.037+/-0.002% (v/v), PANC-1 at 0.0058 +/- 0.0004%
      and BxPC-3 at 0.021 +/- 0.003%. DC at 0.0033% combined with 1 nM of paclitaxel
      showed inhibition synergy on PANC-1 cells with a combination index of 0.44.
      Apoptosis focused antibody array profile indicated upregulation of cytochrome C,
      claspin, cIAP-2 and HTRA2/Omi apoptosis-related markers in DC-treated HP62 and
      PANC-1. Our data suggest that DC acts through targeting the intrinsic
      mitochondrial apoptosis pathway in the pancreatic cancer cells. The high
      antiproliferation potency of DC on PANC-1 is potentially useful as an adjunct
      therapy for treating pancreatic cancer, which is known for developing resistance
      to conventional chemotherapeutics.

PMID- 26221770
TI  - Rheology-modulated contact line dynamics of an immiscible binary system under
      electrical double layer phenomena.
AB  - We investigate the electrically driven contact line dynamics of a binary fluid
      system constituted by one Newtonian and another non-Newtonian fluid in a narrow
      fluidic channel with chemically patched walls. We use a power-law model to
      describe the rheology of the non-Newtonian fluid and a diffuse interface phase
      field method to model the dynamics of multiple phases. We bring out the
      alteration in the interfacial dynamics as attributable to the rheology-driven
      modifications in the interfacial stress and its interplay with the Maxwell stress
      originating from electrokinetic effects. 

PMID- 26221769
TI  - Alpha-1 Antitrypsin Mitigates the Inhibition of Airway Epithelial Cell Repair by
      Neutrophil Elastase.
AB  - Neutrophil elastase (NE) activity is associated with many destructive lung
      diseases and is a predictor for structural lung damage in early cystic fibrosis
      (CF), which suggests normal maintenance of airway epithelium is prevented by
      uninhibited NE. However, limited data exist on how the NE activity in airways of
      very young children with CF affects function of the epithelia. The aim of this
      study was to determine if NE activity could inhibit epithelial homeostasis and
      repair and whether any functional effect was reversible by antiprotease alpha-1
      antitrypsin (alpha1AT) treatment. Viability, inflammation, apoptosis, and
      proliferation were assessed in healthy non-CF and CF pediatric primary airway
      epithelial cells (pAECnon-CF and pAECCF, respectively) during exposure to
      physiologically relevant NE. The effect of NE activity on pAECCF wound repair was
      also assessed. We report that viability after 48 hours was significantly
      decreased by 100 nM NE in pAECnon-CF and pAECCF owing to rapid cellular
      detachment that was accompanied by inflammatory cytokine release. Furthermore,
      both phenotypes initiated an apoptotic response to 100 nM NE, whereas >= 50 nM NE
      activity significantly inhibited the proliferative capacity of cultures. Similar
      concentrations of NE also significantly inhibited wound repair of pAECCF, but
      this effect was reversed by the addition of alpha1AT. Collectively, our results
      demonstrate free NE activity is deleterious for epithelial homeostasis and
      support the hypothesis that proteases in the airway contribute directly to CF
      structural lung disease. Our results also highlight the need to investigate
      antiprotease therapies in early CF disease in more detail.

PMID- 26221771
TI  - Polycyclic Polyprenylated Xanthones from Symphonia globulifera: Isolation and
      Biomimetic Electrosynthesis.
AB  - Two regioisomeric polycyclic xanthones, 3,16-oxyguttiferone A (2) and 1,16
      oxyguttiferone A (3), which are polyprenylated acylphloroglucinol-derived
      analogues, were isolated from the seeds of Symphonia globulifera, together with
      their presumed o-dihydroxybenzoyl precursor, guttiferone A (1). Anodic oxidation
      of 1 into the corresponding o-quinone species proved to be an efficient
      biomimetic method to generate xanthones 2 and 3 in high overall yield and to
      confirm their structures. Both compounds displayed cytotoxicity against the HCT
      116 colon carcinoma cell line with IC50 values of 8 and 3 MUM, respectively.

PMID- 26221772
TI  - MicroRNA-Let-7a regulates the function of microglia in inflammation.
AB  - Microglia have multiple functions in cerebrovascular and neurodegenerative
      diseases. Regulation of microglial function during inflammatory stress is
      important for treatment of central nervous system (CNS) diseases because
      microglia secrete various substances that affect neurons and glia. MicroRNA-Let
      7a (miR-Let-7a) is a tumor suppressor miRNA that has been reported to target
      transcripts that encode proteins involved in apoptosis. In the present study, we
      examined the essential role of miR-Let-7a in inflammatory stress by over
      expressing miR-Let-7a to investigate its role in determining the BV2 microglial
      phenotype, a cell line often used as a model of activated microglia. We found
      that inflammatory factors and Reactive Oxygen Species (ROS) production levels
      were altered according to miR-Let-7a expression level as measured by Western blot
      analysis, reverse transcription PCR, quantitative real time PCR, the measurement
      of nitrite (indicative of the nitric oxide (NO) pathway), and immunocytochemistry
      (ICC). Our results suggest that miR-Let-7a is involved in the function of
      microglia in the setting of inflammatory injury. In response to inflammation, miR
      Let-7a participates in the reduction of nitrite production and the expression of
      inducible nitric oxide synthase (iNOS), interleukin (IL)-6 and is involved in
      increased expression of brain derived neurotrophic factor (BDNF), interleukin
      (IL)-10, and IL-4 in microglia. Thus, miRNA-Let-7a could act as a regulator of
      the function of microglia in inflammation. 

PMID- 26221773
TI  - 8-Nitro-cGMP Enhances SNARE Complex Formation through S-Guanylation of Cys90 in
      SNAP25.
AB  - Nitrated guanine nucleotide 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro
      cGMP) generated by reactive oxygen/nitrogen species causes protein S-guanylation.
      However, the mechanism of 8-nitro-cGMP formation and its protein targets in the
      normal brain have not been identified. Here, we investigated 8-nitro-cGMP
      generation and protein S-guanylation in the rodent brain. Immunohistochemistry
      indicated that 8-nitro-cGMP was produced by neurons, such as pyramidal cells and
      interneurons. Using liquid chromatography-tandem mass spectrometry, we determined
      endogenous 8-nitro-cGMP levels in the brain as 2.92 +/- 0.10 pmol/mg protein.
      Based on S-guanylation proteomics, we identified several S-guanylated neuronal
      proteins, including SNAP25 which is a core member of the soluble N-ethylmaleimide
      sensitive factor attachment protein receptor (SNARE) complex. SNAP25 post
      translational modification including palmitoylation, phosphorylation, and
      oxidation, are known to regulate neurotransmission. Our results demonstrate that
      S-guanylation of SNAP25 enhanced the stability of the SNARE complex, which was
      further promoted by Ca(2+)-dependent activation of neuronal nitric oxide
      synthase. Using site-directed mutagenesis, we identified SNAP25 cysteine 90 as
      the main target of S-guanylation which enhanced the stability of the SNARE
      complex. The present study revealed a novel target of redox signaling via protein
      S-guanylation in the nervous system and provided the first substantial evidence
      of 8-nitro-cGMP function in the nervous system. 

PMID- 26221777
TI  - The outcomes of "atypical" and "suspicious" bile duct brushings in the
      identification of pancreaticobiliary tumors: Follow-up analysis of surgical
      resection specimens.
AB  - BACKGROUND: Bile duct brushing cytology is frequently used to investigate
      suspected pancreaticobiliary tumors, but it is associated with low diagnostic
      sensitivity. As recently proposed by the Papanicolaou Society of Cytopathology in
      its new classification scheme for pancreaticobiliary cytology, the use of
      "atypical" and "suspicious (for malignancy)" categories may give a better
      prediction of malignancy and improve patient management. METHODS: A series of 65
      "atypical" and "suspicious" results initially diagnosed at the University of
      Washington and Harborview Medical Centers between 2005 and 2012 were analyzed to
      determine outcomes based on the review of subsequent surgical resection
      specimens. RESULTS: Seven of 15 (47%) "atypical" cases demonstrated malignant
      outcomes, whereas 49 of 50 (98%) "suspicious" cases showed documented malignancy
      within a mean follow-up of 4 months (P < 0.0001 from Pearson's chi-squared test).
      The analysis of surgical resection specimens demonstrates that 59% of "atypical"
      and "suspicious" bile duct brushings with malignant outcomes were pancreatic
      adenocarcinoma (95% confidence interval (CI): 46-71%), 97% of pancreatic
      adenocarcinomas caused strictures in the head of the pancreas (95% CI: 86-100%),
      and that 86% of pancreatic adenocarcinomas were moderate to poorly differentiated
      (95% CI: 73-99%). Fifty-three of the 60 (88%) patients in the presence of prior
      stenting had a histologically confirmed malignancy. CONCLUSION: The use of
      "atypical" and "suspicious" categories may allow more accurate surveillance
      and/or more rapid surgical exploration of pancreaticobiliary tumors.

PMID- 26221778
TI  - Synthesis and In Vitro Activity of Polyhalogenated 2-phenylbenzimidazoles as a
      New Class of anti-MRSA and Anti-VRE Agents.
AB  - A series of novel polyhalogenated 2-phenylbenzimidazoles have been synthesized
      and evaluated for in vitro antistaphylococcal activity against drug-resistant
      bacterial strains (methicillin-resistant Staphylococcus aureus, and vancomycin
      resistant Enterococcus faecium. Certain compounds inhibit bacterial growth
      perfectly. 11 was active than vancomycin (0.78 MUg/mL) with the lowest MIC values
      with 0.19 MUg/mL against methicillin-resistant Staphylococcus aureus, 8 and 35
      exhibited best inhibitory activity against vancomycin-resistant Enterococcus
      faecium (1.56 MUg/mL). The mechanism of action for this class of compounds
      appears to be different than clinically used antibiotics. These polyhalogenated
      benzimidazoles have potential for further investigation as a new class of potent
      anti-methicillin-resistant Staphylococcus aureus and anti-vancomycin-resistant
      Enterococcus faecium agents.

PMID- 26221779
TI  - Aggressive Squamous Cell Carcinoma Within A Burn Scar Complicated by M. Fortuitum
      Infection: Combination Treatment With Antibiotic Therapy, Mohs Surgery, Amnion
      Chorion Graft, and Low-Intensity Pulsed Dye Laser.

PMID- 26221780
TI  - Medicinal plants with anti-inflammatory activities.
AB  - Medicinal plants have been the main remedy to treat various ailments for a long
      time and nowadays, many drugs have been developed from traditional medicine. This
      paper reviews some medicinal plants and their main constituents which possess
      anti-inflammatory activities useful for curing joint inflammation, inflammatory
      skin disorders, cardiovascular inflammation and other inflammatory diseases.
      Here, we provide a brief overview of quick and easy reading on the role of
      medicinal plants and their main constituents in these inflammatory diseases. We
      hope that this overview will shed some light on the function of these natural
      anti-inflammatory compounds and attract the interest of investigators aiming at
      the design of novel therapeutic approaches for the treatment of various
      inflammatory conditions. 

PMID- 26221781
TI  - Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient
      Astrocytes.
AB  - Astrocytes take up glutamate in the synaptic area subsequent to glutamatergic
      transmission by the aid of high affinity glutamate transporters. Glutamate is
      converted to glutamine or metabolized to support intermediary metabolism and
      energy production. Glutamate dehydrogenase (GDH) and aspartate aminotransferase
      (AAT) catalyze the reversible reaction between glutamate and alpha-ketoglutarate,
      which is the initial step for glutamate to enter TCA cycle metabolism. In
      contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and
      aspartate. We have investigated the role of GDH in astrocyte glutamate and
      glucose metabolism employing siRNA mediated knock down (KD) of GDH in cultured
      astrocytes using stable and radioactive isotopes for metabolic mapping. An
      increased level of aspartate was observed upon exposure to [U-(13) C]glutamate in
      astrocytes exhibiting reduced GDH activity. (13) C Labeling of aspartate and TCA
      cycle intermediates confirmed that the increased amount of aspartate is
      associated with elevated TCA cycle flux from alpha-ketoglutarate to oxaloacetate,
      i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient
      astrocytes as observed by increased de novo synthesis of aspartate via pyruvate
      carboxylation. In the absence of glucose, lactate production from glutamate via
      malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies
      reveal that metabolism via GDH serves an important anaplerotic role by adding net
      carbon to the TCA cycle. A reduction in GDH activity seems to cause the
      astrocytes to up-regulate activity in pathways involved in maintaining the amount
      of TCA cycle intermediates such as pyruvate carboxylation as well as utilization
      of alternate substrates such as branched chain amino acids.

PMID- 26221782
TI  - Highly Efficient Rh-Catalyzed Asymmetric Hydrogenation of alpha,beta-Unsaturated
      Nitriles.
AB  - A highly efficient enantioselective hydrogenation of alpha,beta-unsaturated
      nitriles catalyzed by Rh-(R,R)-f-spiroPhos complex has been developed. With Rh
      (R,R)-f-spiroPhos catalyst and under mild conditions, a wide range of alpha,beta
      unsaturated nitriles including the (E)- and (Z)-isomers of 3-alkyl-3-aryl, 3,3
      diaryl, and 3,3-dialkyl alpha,beta-unsaturated nitriles were hydrogenated to the
      corresponding chiral nitriles with excellent enantioselectivities (up to 99.9%
      ee) and high turnover numbers (TON up to 10,000). 

PMID- 26221783
TI  - Novel fiber-rich lentil flours as snack-type functional foods: an extrusion
      cooking effect on bioactive compounds.
AB  - Novel snack-type functional foods based on extruded lentil flours could convey
      the related health benefit of their bioactive compounds, provide a gluten-free
      alternative to consumers, and potentially increase the consumption of pulses.
      Extrusion treatment promoted an increase in galactopinitol, ciceritol, raffinose,
      stachyose and total alpha-galactoside content, in most lentil flours. As alpha
      galactosides may act as prebiotics, they could convey beneficial effects to human
      and monogastric animals. Conversely, extrusion significantly (p < 0.05) reduced
      the inositol hexaphosphate content to less phosphorylated phytates (inositol
      pentaphosphate and inositol tetraphosphate), which provide health effects. The
      gluten-free formulation (control formulation #3) presented the highest
      significant (p < 0.05) drop in the inositol hexaphosphate of 14.7-fold decrease,
      but had a large increase in inositol pentaphosphate, due to extrusion processing.
      These two results are desirable in the finished product. Extrusion also caused a
      significant (p < 0.05) reduction in the trypsin content and completely
      inactivated lectin, in all processed samples. 

PMID- 26221784
TI  - On Deployment and Military Suicide Risk--Reply.

PMID- 26221785
TI  - Improved stoichiometry and photoanode efficiency of thermally evaporated CdS film
      with quantum dots as precursor.
AB  - Good stoichiometry of cadmium sulfide (CdS) film facilitates its application in
      photovoltaic devices; however, traditional thermal evaporation usually results in
      a Cd-deficient CdS film at a low-substrate temperature. In this study, Cd-rich
      CdS quantum dots (QDs) were synthesized by a facile co-precipitation method and
      used as the precursor to thermally evaporate CdS film on indium tin oxide-coated
      glass (ITO/glass). As a consequence, the stoichiometry of CdS film was greatly
      improved with atomic ratio of Cd to S restored to unity. More importantly, the
      newly developed CdS film, with its rod-like surface microstructure, acted as an
      efficient photoanode in a photoelectrochemical (PEC) cell. Its properties,
      including surface morphology and roughness, crystal structure, chemical
      composition, film thickness, energy-level structure and photosensitivity, are
      studied in detail. 

PMID- 26221786
TI  - Using a Multimedia Presentation to Enhance Informed Consent in a Pediatric
      Emergency Department.
AB  - BACKGROUND: Informed consent is an ethical process for ensuring patient autonomy.
      Multimedia presentations (MMPs) often aid the informed consent process for
      research studies. Thus, it follows that MMPs would improve informed consent in
      clinical settings. OBJECTIVE: The aim of this study was to determine if an MMP
      for the informed consent process for ketamine sedation improves parental
      satisfaction and comprehension as compared with standard practice. METHODS: This
      2-phase study compared 2 methods of informed consent for ketamine sedation of
      pediatric patients. Phase 1 was a randomized, prospective study that compared the
      standard verbal consent to an MMP. Phase 2 implemented the MMP into daily work
      flow to validate the previous year's results. Parents completed a survey
      evaluating their satisfaction of the informed consent process and assessing their
      knowledge of ketamine sedation. Primary outcome measures were parental overall
      satisfaction with the informed consent process and knowledge of ketamine
      sedation. RESULTS: One hundred eighty-four families from a free-standing, urban,
      tertiary pediatric emergency department with over 85,000 annual visits were
      enrolled. Different demographics were not associated with a preference for the
      MMP or improved scores on the content quiz. Intervention families were more
      likely "to feel involved in the decision to use ketamine" and to understand that
      "they had the right to refuse the ketamine" as compared with control families.
      The intervention group scored significantly higher overall on the content section
      than the control group. Implementation and intervention families responded
      similarly to all survey sections. CONCLUSIONS: Multimedia presentation improves
      parental understanding of ketamine sedation, whereas parental satisfaction with
      the informed consent process remains unchanged. Use of MMP in the emergency
      department for informed consent shows potential for both patients and providers.

PMID- 26221787
TI  - Symptomatic Presentation of an Anamalous Left Coronary Artery from the Pulmonary
      Artery in an 8-Day-Old.
AB  - An 8-day-old presented in extremis and was subsequently diagnosed with an
      anomalous left coronary artery from the pulmonary artery. Symptomatic
      presentation at her young age and atypical echocardiogram findings make this case
      unique and suggest that demonstration of retrograde coronary flow is unnecessary
      in symptomatic presentation. 

PMID- 26221788
TI  - Radiologic, Neurologic and Cardiopulmonary Aspects of Submersion Injury.
AB  - Many indices and scores are used in critical care medicine to aid management and
      predict risk of mortality. We report 2 cases of submersion injury and discuss the
      usefulness and application of common respiratory and critical care indices. The
      respiratory indices help better understand the pulmonary pathophysiology and
      characterize the severity of lung injury and ventilation/perfusion mismatch.
      Severe lung injury resolved after ventilation support with appropriate positive
      end-expiratory pressure in both cases. The 6-year-old girl survived the near
      fatal submersion injury intact despite grossly abnormal initial Glasgow Coma
      Scale (GCS) and high Pediatric Index of Mortality 2 scores, whereas the 5-year
      old boy with grossly abnormal GCS and Pediatric Index of Mortality 2 scores died
      despite resolution of lung injury. These cases illustrate that resuscitation
      should be promptly instituted at the scene to ensure optimal outcome because
      initial pulmonology and neurology indices may not reliably predict mortality or
      intact survival. The GCS score was not initially designed for prognostication.
      Nevertheless, 2 serial GCS scores of 3, one performed at emergency department and
      one at the pediatric intensive care unit, were associated with nonsurvival in our
      second patient. 

PMID- 26221789
TI  - Implementation of an Advanced Nursing Directive for Children With Right Lower
      Quadrant Pain: Identifying Those Requiring Further Investigation and Improving
      Flow Metrics.
AB  - OBJECTIVES: Advanced nursing directives (ANDs) empower nursing staff to provide
      advanced levels of care before physician assessment. The objectives of this study
      were (1) to determine whether an AND for right lower quadrant (RLQ) pain could
      identify children who required any further investigation to diagnose appendicitis
      and (2) to determine whether children meeting AND criteria had better emergency
      department (ED) flow metrics compared with those who did not meet the criteria.
      METHODS: Health records of children aged 3 to 17 years presenting to the ED with
      abdominal pain who were managed using the departmental AND for RLQ pain were
      reviewed. Primary outcomes included (1) the proportion of patients requiring
      further investigation to diagnose appendicitis and (2) the time interval from
      triage to blood draw. Secondary outcomes included additional ED flow metrics,
      perforation rate, and negative appendectomy rate. RESULTS: An AND was completed
      for 210 children. Those who met the AND criteria were more likely to undergo
      further investigation to rule out appendicitis than those who did not meet the
      criteria (92/137 [67.2%] vs 32/73 [43.8%]; odds ratio [OR], 2.62; 95% confidence
      interval [CI], 1.40-4.90). Time to blood draw was significantly lower for those
      children meeting the AND criteria (74 vs 162 minutes, P < 0.001) as was time to
      hospital admission (271 vs 395 minutes, P = 0.008) and appendectomy (498 vs 602
      minutes, P = 0.015). The negative appendectomy rate was 8.6% (5/58) for children
      meeting the AND criteria and 9.1% (2/22) for those not meeting the criteria (OR,
      0.94; 95% CI, 0.14-10.67); the perforation rate was 29.3% (17/58) and 4.5%
      (1/22), respectively (OR, 8.17; 95% CI, 1.17-380.86). CONCLUSIONS: Children
      presenting to the ED with RLQ pain who meet the AND criteria are more likely to
      require further investigation to rule out appendicitis and have better department
      flow metrics than those who do not meet the criteria. Our results provide further
      evidence of the utility of ANDs in the ED.

PMID- 26221790
TI  - A Curiously Rare Case of Septic Shock From Clostridium difficile Colitis.
AB  - This case provides the first report of a young healthy child presenting in septic
      shock from Clostridium difficile colitis. This child had no identifiable risk
      factors for C. difficile, raising the suspicion for a hypervirulent strain. Once
      infection was recognized and treated appropriately, the child made a full
      recovery. This case presentation highlights the need to consider C. difficile
      colitis in the differential diagnosis of severely ill patients, even in the
      absence of traditional risk factors or symptoms.

PMID- 26221792
TI  - Young drivers' night-time mobility preferences and attitude toward alcohol
      consumption: A Hybrid Choice Model.
AB  - This paper proposes an analysis of mobility preferences of young people at
      nighttime. In OECD countries in the last decades, data show that road crashes are
      the single biggest cause of death of 15-24 years-old drivers. On average, over
      8500 young drivers were killed each year and it is demonstrated that the
      accidents tend to occur on weekend nights and when young people drive under the
      influence of alcohol. Focusing on the demand for mobility, we approach the
      problem from several points of view, concentrating on the relationship between
      attitudes towards alcohol and some of the most common countermeasures implemented
      to address young-driver risk. In particular, we examine the potential demand of
      young drivers for new modes of public transport, understand their preferences for
      plans designed to reduce and/or prevent the number of risky situations. Our
      analysis covers different aspects of private modes of transport, including
      amounts of fines and police checkpoints. We also investigate the characteristics
      of existing and available public transport systems (e.g. fares and levels of
      services). Through a Stated Preferences experiment (SP), we collected young
      people's preferences about nighttime mobility within our application area
      (Lugano, Switzerland). Using the Hybrid Choice Models technique, we developed an
      approach and we estimated a model designed to incorporate simultaneously three
      dimensions of the problem: attributes of the alternatives, characteristics of
      young drivers, and alcohol-related psychological variables. Our estimates suggest
      that, first, there are young drivers who are willing to choose public
      alternatives; secondly, the countermeasures considered can increase their number;
      and, thirdly, people with a higher attitude to alcohol are more willing to switch
      to new public transport alternatives and more sensitive to "Drinking and Driving
      Do not Mix" policies. Action plans developed on the basis of these findings and
      on the relevance of the psychological component will have a better chance to
      succeed. 

PMID- 26221791
TI  - Female Adolescent Presenting With Abdominal Pain: Accidental Wire Bristle
      Ingestion Leading to Colonic Perforation.
AB  - INTRODUCTION: Abdominal pain in female adolescents is a common presentation to
      both the emergency department and the outpatient pediatric clinic. The broad
      differential diagnosis for abdominal pain requires a high index of suspicion to
      make an accurate diagnosis of foreign body ingestion as the etiology. Foreign
      body ingestion occurs in all age groups, but sequelae of gastrointestinal tract
      perforation in children are rare. Treatment for perforation requires consultation
      of the pediatric general surgeon. Clinicians should take care to not overlook
      subtle imaging findings or dietary/exposure history, even in the context of a
      patient with known history of abdominal pain. CASE REPORT/TECHNIQUE DESCRIPTION:
      We report the accidental ingestion of a wire bristle from a grill cleaning brush
      by a female adolescent. The patient, previously treated and seen for constipation
      and irritable bowel syndrome in the outpatient gastroenterology clinic, was
      referred to the emergency department after identification of a foreign body on
      abdominal radiography. Emergency department physicians discovered the history of
      grilling and consumption of grilled food, facilitating diagnosis of a wire
      bristle as the foreign body. The metallic foreign body had migrated to the colon,
      where it perforated and lodged into the abdominal wall, causing acute, focal
      symptoms. Observation in the hospital with pain control and infection management
      allowed for elective laparoscopy. The surgical team removed the object with
      minimal morbidity and avoided laparotomy. DISCUSSION: Reports of unintended
      ingestion of wire bristles have been increasingly reported in the literature;
      however, most focus on injury to the upper airway or upper digestive tract and
      subsequent endoscopic or laryngoscopic removal. Most reports detail injury in
      adult patients, pediatric case reports with digestive tract injury are uncommon,
      and foreign body removal after lower digestive tract injury in children from a
      wire bristle has not been reported. We caution pediatric emergency medicine and
      ambulatory providers to consider such an ingestion and perforation in the
      differential diagnosis of acute-onset, focal, and localizable abdominal pain in
      children.

PMID- 26221793
TI  - Reconstitution of Functionalized Transmembrane Domains of Receptor Proteins into
      Biomimetic Membranes.
AB  - For integral membrane proteins, an assessment of their structures and
      interactions within a biomimetic lipid bilayer environment is critical for
      evaluating their cellular function. Hydrophobic sequences prevalent within
      transmembrane domains, however, make these proteins susceptible to aggregation
      and, thus, create difficulties in examining their structural and functional
      properties via canonical techniques. Working exclusively with single-pass
      transmembrane (TM) segments of bitopic membrane proteins, in the form of soluble
      peptides, bypasses many of the pitfalls of full-length protein preparations while
      allowing for the opportunity to examine the properties of TM domains within
      biomimetic membrane environments. In this study, peptides mimicking the TM
      domains of the epidermal growth factor receptor (EGFR) and CD4 co-receptor, both
      cell-signaling surface receptors, have been reconstituted into 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers. The formation of their
      native alpha-helical structures within vesicle membranes was observed from
      circular dichroism, and full partition of the peptides into the membrane was
      demonstrated by tryptophan fluorescence and neutron reflectivity (NR). Using an
      engineered planar lipid bilayer system ideal for surface characterization
      methods, such as surface plasmon resonance (SPR) and NR, the TM peptides,
      functionalized with a N-terminal biotin tag, proved capable of "activating" a
      membrane surface, as evidenced by the capture of streptavidin. On the basis of
      these initial assessments, we anticipate these membrane-bound peptides will
      provide a versatile platform for understanding the intricate roles of receptor TM
      domains in cell signaling. 

PMID- 26221794
TI  - Tackling the double burden of malnutrition across the life course: a global
      imperative.

PMID- 26221795
TI  - Nutrition-sensitive agriculture and the promotion of food and nutrition
      sovereignty and security in Brazil.
AB  - This paper explores the possibilities of the nutrition-sensitive agriculture
      approach in the context of the programs and actions towards promoting food and
      nutrition sovereignty and security in Brazil. To analyze the links between
      nutrition and agriculture, this paper presents the conceptual framework related
      to food and nutrition security, and stresses the correlations among concepts,
      institutional structures and program design in Brazil. Dominant models of food
      production and consumption are scrutinized in the light of these relationships.
      This paper also highlights differences amongst different ways to promote
      nutrition-sensitive agriculture through food-acquisition programs from family
      farmers, experiences in agro-ecology and bio-fortification programs. In the
      closing remarks, the paper draws some lessons learned from the Brazilian
      experience that highlight the advantages of family farming and rapid food
      production, distribution and consumption cycles in order to promote access to an
      affordable, diversified and more adequate diet in nutritional terms.

PMID- 26221796
TI  - [Consumption of fruit and vegetables and the health conditions of men and women
      attended in the primary healthcare network].
AB  - This cross-sectional study sought to analyze the associations between health
      conditions and the inadequate consumption of fruit and vegetables (FV) of 1,255
      men and women attended in Primary Healthcare Units in Belo Horizonte (State of
      Minas Gerais). Data collection included FV consumption, socioeconomic status and
      health conditions. Results are presented by prevalence ratio (PR) with a
      confidence interval of 95% (CI 95%). A 77.5% (CI 95%: 75.1%-79.8%) of inadequacy
      of consumption (< 5 daily servings) was found and it was more prevalent among men
      (83.8%, CI 95%: 79.0%-88.5% than among women: 76.0%, CI 95%: 73.4%-78.6%). For
      women, the inadequate consumption of FV was higher among those with poor
      perception of health quality (PR: 1.37; CI 95%: 1.19-1.59) and among those who
      consider their dietary habits as being unhealthy (PR: 1.15; CI 95%: 1.07-1.24).
      For men, the inadequate consumption was higher between individuals that reported
      2 to 4 visits to the doctor in the year prior to the interview (PR: 1.21; CI 95%:
      1.06-1.21). The conclusions showed that the consumption of FV among the
      population under study is below the recommendations and the health conditions are
      associated differently for each gender.

PMID- 26221797
TI  - [The nutritional status of Kaingang and Guarani indigenous peoples in the State
      of Parana, Brazil].
AB  - This study arose from the need to comprehend epidemiological aspects to establish
      a policy for physical activity for indigenous peoples. Although infectious
      diseases are still the main causes of suffering in these ethnic groups, chronic
      diseases have emerged due to the process of epidemiological/nutritional change in
      indigenous peoples subject to the policy of life on reservations. The scope of
      this study was to evaluate the nutritional status of indigenous peoples belonging
      to two ethnic groups in the State of Parana. Anthropometric data were collected
      on 178 adults belonging to the Kaingang (n = 117) and Guarani (n = 61) indigenous
      ethnic groups. The prevalence of being overweight in Guarani and Kaingang adults
      was 32.3% and 41%, respectively, detecting a prevalence of obesity in the order
      of 3.2% among the Guarani indigenous people and 12.8% among the Kaingang ethnic
      group. Anthropometric changes observed among the Guarani and Kaingang indigenous
      peoples of Parana are of increasing concern according to some studies. Thus, the
      results of this study reinforce the need for integrated actions such as
      nutritional guidance and physical activity during leisure time for the promotion
      of the health of these populations.

PMID- 26221798
TI  - [Street food: analysis of hygienic and sanitary conditions of food handlers].
AB  - The consumption of street food is an economical and practical alternative for the
      population. However, concerns regarding the safety of these foods are increasing.
      Thus, this study aimed to analyze the hygienic and sanitary conditions of the
      street food trade in Uberaba in the State of Minas Gerais. For this purpose, 30
      street vending sites were evaluated using a structured questionnaire and
      microbiological analysis of food handlers' hands and food contact recipients and
      surfaces. The findings showed low adequacy of street food regarding hand hygiene
      and food contact surfaces. With respect to surfaces, the results for mesophilic
      aerobic microorganisms revealed that only 23.3% had satisfactory sanitary
      conditions. The level of contamination of hands by fecal thermotolerant coliforms
      and/or Coagulase positive Staphylococci was unsatisfactory in approximately 47%
      of food handlers. The conclusion drawn is that the hygienic and sanitary
      conditions of food handlers in Uberaba are poor. It is therefore necessary to
      adopt effective and permanent training programs on food safety for food handlers
      urgently. 

PMID- 26221799
TI  - [Translation and cultural adaptation of the questionnaire on the reason for food
      choices (Food Choice Questionnaire - FCQ) into Portuguese].
AB  - The Food Choice Questionnaire (FCQ) assesses the importance that subjects
      attribute to nine factors related to food choices: health, mood, convenience,
      sensory appeal, natural content, price, weight control, familiarity and ethical
      concern. This study sought to assess the applicability of the FCQ in Brazil; it
      describes the translation and cultural adaptation from English into Portuguese of
      the FCQ via the following steps: independent translations, consensus, back
      translation, evaluation by a committee of experts, semantic validation and pre
      test. The pre-test was run with a randomly sampled group of 86 male and female
      college students from different courses with a median age of 19. Slight
      differences between the versions were observed and adjustments were made. After
      minor changes in the translation process, the committee of experts considered
      that the Brazilian Portuguese version was semantically and conceptually
      equivalent to the English original. Semantic validation showed that the
      questionnaire is easily understood. The instrument presented a high degree of
      internal consistency. The study is the first stage in the process of validating
      an instrument, which consists of face and content validity. Further stages,
      already underway, are needed before other researchers can use it.

PMID- 26221800
TI  - [The influence of breastfeeding in the hospitalization of children under two
      years of age in the State of Pernambuco, Brazil, in 1997 and 2006].
AB  - The scope of this paper was to evaluate the influence of breastfeeding and other
      factors on the incidence of hospitalization and the frequency and main causes of
      hospitalization in children under two years of age in the State of Pernambuco. It
      is a cross-sectional, descriptive-analytical study using secondary data obtained
      from the II and III State Health and Nutrition Surveys (PESN) carried out in 1997
      and 2006, respectively. A sample of 1503 infants under two years of age was
      studied. Pearson's Chi-square test was used to analyze bivariate associations and
      Fisher's exact test for comparison of risk of hospitalization in the two years of
      observation and Poisson regression for the adjustment of the multivariate model
      of hospitalizations in the last survey. In the two years analyzed, there was no
      statistically significant difference in the percentage of hospitalizations of
      children. The lower risk of hospitalization remained for those who were breastfed
      exclusively. Regarding to environmental, socioeconomic, demographic
      characteristics and health assistance, several factors have evolved favorably in
      the period assessed. In the final model, only the weight/length ratio (low weight
      category) remained associated with the risk of hospitalization in children under
      two years of age factors.

PMID- 26221801
TI  - [Evaluation of the Food and Nutrition Surveillance System (SISVAN) in food and
      nutritional management services in the State of Minas Gerais, Brazil].
AB  - The scope of this article is to evaluate the SISVAN as a tool for planning,
      management and evaluation of food and nutrition actions in primary healthcare in
      the Unified Health System (SUS). It involved a cross-sectional study composed of
      a stratified random sample of the municipalities in the State of Minas Gerais.
      The subjects of the research were municipal officials of SISVAN who filled out a
      structured questionnaire. Descriptive analysis of the data was performed with the
      construction of simple and bivariate tables. It was observed that those
      responsible for SISVAN, collect (50%) and input (55%) weight, height, and food
      consumption data; whereas 53%, 59% and 71% do not analyze and do not recommend or
      perform nutrition actions, respectively. This being the case, most of those
      responsible do not use the information for planning, management and evaluation of
      food and nutrition traits. The findings show that the SISVAN is not used to its
      full potential; the data generated have not been used for planning, management
      and evaluation of nutrition services in primary healthcare in the SUS.

PMID- 26221802
TI  - [Factors associated with the consumption of soft drinks among Brazilian preschool
      children: national survey of 2006].
AB  - The rising consumption of sweetened beverages such as soft drinks or artificial
      juices is associated with the prevalence of obesity in Brazil and around the
      world. This study seeks to verify the frequency of consumption of these beverages
      among Brazilian children aged 24-59 months and to investigate the association of
      soft drinks with demographic, socioeconomic and nutritional variables. Using data
      from the National Survey on Demography and Health of Women and Children - 2006,
      the eating habits were obtained using the food and drink frequency questionnaire
      for the seven days preceding the interview, and anthropometry recorded the weight
      and height of children. Among preschoolers, 37.3% consumed soft drinks and
      artificial juices 4 or more days per week. The factors significantly associated
      with frequent consumption of soft drinks were living in regions of higher
      economic development of the country, in urban areas, belonging to the higher
      income bracket, with mothers watching TV regularly and excess weight of the
      child, were associated with consumption of soft drinks and artificial juices 4 or
      more days per week. Further studies are needed to understand the effective
      contribution of soft drinks on the epidemic of childhood obesity.

PMID- 26221803
TI  - Obesity parameters as predictors of early development of cardiometabolic risk
      factors.
AB  - The scope of this study was to verify the association between different
      overweight and obesity parameters and the metabolic risk profile among school-age
      students. The randomized cross-sectional study included 1254 children and
      adolescents, aged 7 to 17, from a city in southern Brazil. Body mass index (BMI),
      waist circumference (WC) and percentage of fat (PF), measured at the triceps and
      based on subscapular skinfold thickness, were used as the parameters to evaluate
      overweight/obesity status. Systolic blood pressure (SBP), total cholesterol, high
      density lipoprotein cholesterol (HDL), low-density protein cholesterol (LDL) and
      triglycerides were also measured. The metabolic risk profile was calculated based
      on the sum of the z score of the metabolic variables adjusted by age. A three
      model Poisson analysis was used to verify the association between BMI, WC and PF
      with metabolic risk profile. BMI showed the highest probability for developing
      metabolic risk compared with WC (overweight - PR: 1.63 and obesity - PR: 3.87)
      and PF (overweight - PR: 1.62 and obesity - PR: 2.92). In conclusion, BMI seems
      to be a better parameter of overweight/obesity than WC and PF in the assessment
      of metabolic risk among youths.

PMID- 26221804
TI  - [Healthy eating and the difficulties faced in making it a reality: perceptions of
      parents/guardians of pre-school children in Belo Horizonte/MG, Brazil].
AB  - A cross-sectional qualitative study was conducted to establish the perceptions of
      77 guardians of preschool children enrolled in a Child Day Care Center in Belo
      Horizonte/Minas Gerais State, regarding what is a healthy diet and the
      difficulties faced in having a healthy diet. The instrument used was a pretested
      semi-structured questionnaire containing leading questions obtained in face-to
      face interviews. For data analysis, the Collective Subject Discourse technique
      was used, which elicited data organization of a verbal nature. It was revealed
      that the guardians have a notion of what healthy diet is, however their answers
      implied inadequate eating habits. They attributed insufficient financial
      resources, lack of time and ingrained eating habits as being the main
      difficulties in having a healthy diet. These three difficulties are the reasons
      given by some guardians who do not believe they have a healthy diet. The
      conclusion drawn is that the guardians need to have a better diet, because their
      eating habits influence their children's eating habits. These findings revealed
      the need for food and nutrition education strategies to enable the guardians to
      recognize and have a healthy diet.

PMID- 26221805
TI  - Alteration in eating habits among shift workers of a poultry processing plant in
      southern Brazil.
AB  - The relationship between shift work and the eatinghabits of workers was
      investigated in a slaughterhouse in southern Brazil. It involved a cross
      sectional study with 1,206 workers of both sexes between 18 and 50 years of age.
      A standardized questionnaire was used to gather demographic, socioeconomic, work
      shift and eating habit information. The shift of work was categorized into
      daytime and nighttime, based on the starting and ending times of the shift. The
      eating habits of workers were evaluated as follows: number and type of meals
      eaten during the 24 hours of a normal day, the inappropriateness of the hoursof
      these meals and the dietaryrisk score. This was built on the risk score of the
      weekly consumption of 13 food items. After adjusting for potential confounders,
      non-Caucasian and younger male workers were more likely to manifest eating risk
      habits. Nighttimeshift workers consumed ahigher number of meals/day with greater
      inappropriateness of meal times than daytimeshift workers. The night shift can
      negatively influence the eating habits of workers of that shift.

PMID- 26221806
TI  - [Overweight and associated variables in schoolchildren in Itajai in the State of
      Santa Catarina, Brazil].
AB  - The research objective was to evaluate the association between socioeconomic and
      demographic variables of health-related behaviors and characteristics of the home
      environment and the prevalence of overweight among students from 1st to 5th grade
      in the city of Itajai in the State of Santa Catarina, brazil. Socioeconomic and
      demographic variables were identified through a questionnaire administered to
      parents/guardians. Nutritional status was determined by body mass index and waist
      circumference. The association between excess weight and other variables was
      investigated using Pearson's Chi-Square and the Linear Trend test. The population
      consisted of 417 children, which represented 95.2% of the sample. The data
      suggest that 44% of children were overweight, which was associated with: a better
      quality diet (49.4%, p = 0.051), lower frequency of consumption of snack foods,
      habit of eating meals while watching the television, overweight parents (51%, p =
      0,002), the score of family nutrition (51.9%, p = 0.029**) and physical activity
      in children. It is suggested that health actions must consider the family
      environment and the social context of children to promote healthier lifestyles.

PMID- 26221807
TI  - The main characteristics of qualitative studies carried out by doctors in Brazil:
      a literature review.
AB  - This paper explores the possibilities of the nutrition-sensitive agriculture
      approach in the context of the programs and actions towards promoting food and
      nutrition sovereignty and security in Brazil. To analyze the links between
      nutrition and agriculture, this paper presents the conceptual framework related
      to food and nutrition security, and stresses the correlations among concepts,
      institutional structures and program design in Brazil. Dominant models of food
      production and consumption are scrutinized in the light of these relationships.
      This paper also highlights differences amongst different ways to promote
      nutrition-sensitive agriculture through food-acquisition programs from family
      farmers, experiences in agro-ecology and bio-fortification programs. In the
      closing remarks, the paper draws some lessons learned from the Brazilian
      experience that highlight the advantages of family farming and rapid food
      production, distribution and consumption cycles in order to promote access to an
      affordable, diversified and more adequate diet in nutritional terms.

PMID- 26221809
TI  - [Construction of a scale to assess the methodological quality of systematic
      reviews].
AB  - The aim of this study was to describe the process of creation and validation of
      methodology to assess the methodological quality of systematic reviews. From the
      expansion of the scope and addition of new items to the Assessment of Multiple
      Systematic Reviews (AMSTAR) instrument evidence of validity and reliability of
      the new methodology was sought. Firstly, the original scale was translated,
      adapted, expanded and evaluated by a panel of five experts. Then it was tested by
      evaluating a random sample of five systematic reviews by three judges with no
      formal training in the scale. Finally, the consolidated scale was assessed in a
      new panel by two judges. The panel of experts reached a consensus regarding the
      validity of the proposed changes. With respect to the scale total and per item
      score, the average agreement between judges was considered satisfactory in the
      consolidated scale. From the processes of adaptation and validation performed,
      the methodology in its final version consisted of 14 items that taken together
      indicate the methodological quality of systematic reviews from different areas of
      knowledge. 

PMID- 26221808
TI  - The Polisemy of Clinical Governance: a review of literature.
AB  - The article aims to explore the concept of clinical management, with a view
      towards understanding the diverse meanings that could be attributed to that
      expression. This discussion can contribute to the planning and organization of
      health services geared to the management of clinical practices, as well as to set
      forth principles to draft actions in that field. Methodologically, the study
      consists of a qualitative literature review, using keywords of the Virtual Health
      Library (VHL). In terms of results, seven topics stand out that synthesize the
      analysis of sources: management, quality promotion, clinical monitoring or
      auditing, education, responsibility or accountability, safety in care and a
      systemic dimension. The conclusion is that the variation of meanings relates to
      the way in which the authors of the studies reviewed express or unfold the
      structuring conceptual components broadly accepted as clinical governance. What
      we observe is a lack of a greater focus on discussions regarding planning and
      policies relating to clinical governance.

PMID- 26221810
TI  - Mario Magalhaes: Development is Health.
AB  - Mario Magalhaes da Silveira (1905-1986) was the main mentor of the school of
      thought known as "developmental public health" whose influence peaked at the III
      National Health Assembly. A critic of the adoption of North American models of
      public health organization, of the centralism and vertical organization of public
      health campaigns and the interference of international bodies, the public health
      doctor held the view that as health is a problem of superstructure, it depends on
      industrial economic development. He also defended the urgent need to municipalize
      public health in order to attend to the real needs of the Brazilian population. A
      pioneer of the intermingling of economic and demographic variables, he may be
      seen as a predecessor of the health economy discipline. The article describes the
      professional path of Mario Magalhaes as a backdrop to his critical thinking on
      specific national situations and the health policies adopted. 

PMID- 26221811
TI  - Attributes of primary health care provided to children/adolescents with and
      without disabilities.
AB  - This study sought to compare the attributes of the Primary Health Care (PHC)
      provided by caregivers of the Family Health Strategy (FHS) to children and
      adolescents with and without physical disabilities in Palmas (State of Tocantins,
      Brazil). This is a cross-sectional, descriptive study with a quantitative
      approach. For data collection, the PCA Tool-Brazil (child version) was applied to
      caregivers of children and adolescents residing and registered in family health
      teams. The attributes of primary care were evaluated through scores measured
      according to the criteria of the instrument. The results indicated that three
      attributes had scores above the cutoff point for the physically disabled
      population and two attributes for the population without disabilities. Overall,
      the data showed no significant differences between children with and without
      disabilities from the standpoint of caregivers. The general score also showed a
      below satisfactory score in both groups. The evaluation of the attributes of the
      PHC was characterized as low-quality care to children and adolescents, be they
      physically challenged or not, which highlights the fact that the biggest
      challenges lie in ensuring health care to children and adolescents.

PMID- 26221812
TI  - Prevalence of neck and upper limb musculoskeletal disorders in artisan
      fisherwomen/shellfish gatherers in Saubara, Bahia, Brazil.
AB  - This study was conducted in an artisanal fishing community. The main health
      complaints included musculoskeletal disorders (MSD) attributable to working
      conditions. The present work found a prevalence of neck and distal upper limb MSD
      among the artisan fisherwomen/shellfish gatherers in Saubara, Bahia, Brazil. This
      was a cross-sectional cohort epidemiological study involving 209 artisanal
      fisherwomen/shellfish gatherers. The Brazilian version of the Job Content
      Questionnaire (JCQ), the Nordic Musculoskeletal Questionnaire (NMQ) and a survey
      listing physical demands adapted to shellfish gathering were used for the study.
      The MSD values obtained in some part of the body, neck or shoulder, and distal
      upper limb were 94.7%, 71.3% and 70.3%, respectively. The shellfish gatherers
      were found to work long shifts despite the high prevalence of MSD. The factors
      that cause these women to keep performing such activities include the need to
      make a living and provide food for their families through the sale and
      consumption of seafood.

PMID- 26221813
TI  - Mental disorders among health workers in Brazil.
AB  - The scope of this article is to deter mine the prevalence of common mental
      disorders (CMD) and Depression among Community Health Agents (CHA) and employees
      of Psychosocial Care Centers (CAPS). It is a cross-sectional descriptive study
      involving the target population of Community Health Workers and Psychosocial Care
      Center workers, linked to the Municipal Health Department of Pelotas in the
      Brazilian State of Rio Grande do Sul. The presence of common mental disorders was
      considered when the Self Report Questionnaire (SRQ) was > 7 and the occurrence of
      depression when BDI > 12. In total, 257 professionals participated in the study.
      Among mental health professionals (n = 119), the prevalence of CMDs was 25.2% and
      depression was 23.5%, while the prevalence of CMDs was 48.6% and depression was
      29% among CHA (n = 138). The ratio of CMDs between the two groups of
      professionals was statistically different (p < 0.001). In this study, it was
      observed that the CAPS professionals are more adapted to work issues, with less
      perceived health problems arising from work and with a lower prevalence of mental
      disorders compared to CHA.

PMID- 26221814
TI  - Factors associated with chronic diseases among the elderly receiving treatment
      under the Family Health Strategy.
AB  - The profile of a sample population of elderly receiving treatment under the
      Family Health Strategy in the municipality of Teofilo Otoni, State of Minas
      Gerais, Brazil, is described, and the factors associated with diseases prevalence
      examined. Using simple random sampling, 385 elderly were interviewed using Form A
      and Elderly Form from the Primary Health Care Information System. The majority of
      the sample (83.1%) self-reported at least one disease, 69.9% had hypertension,
      and 17.7% had diabetes. Poisson regression analysis showed that the main factors
      associated with hypertension and other diseases were being non-white, having a
      low level of education, medication use, dental prosthesis use, and lack of a
      private health plan. The prevalence of diabetes was greater among women and
      individuals who depended on other people to live. It can be concluded that this
      sample population of elderly has a generally low socioeconomic status and are
      more susceptible to developing diseases, particularly hypertension. Diabetes
      should be controlled although had relatively low prevalence. It is suggested
      investments in structuring the health system network to provide adequate care for
      the elderly and in training health professionals to play an effective role in
      improving the quality of life of the elderly in Brazil.

PMID- 26221815
TI  - Evaluation of different school-based preventive interventions for reducing the
      use of psychotropic substances among students: a randomized study.
AB  - Although many schools perform preventive interventions for reducing drug use,
      little is known about their implementation processes and results. Accordingly,
      this study aimed to evaluate the effectiveness of three different types of
      preventive intervention performed in the school setting for reducing substance
      use among students. The study comprised 1316 students from the 9th year of
      elementary school to the 3rd year of secondary school in 8 public schools in the
      city of Guarulhos, Sao Paulo state, Brazil. Students were randomly assigned to
      the intervention groups or a control group and were evaluated at two different
      time-points regarding substance use. The results indicated that interventions
      performed by teachers were most effective in reducing both substance use and the
      severity of substance-associated problems. Interventions performed by experts
      were partially effective, although they only reduced use among experimental
      users. The results of "Single lecture" interventions revealed that such
      approaches are counterproductive. In summary, preventive actions that were
      contextualized to the student's reality and the school environment and that
      included the active involvement of both teacher and student were most effective
      at reducing the prevalence of substance use and the severity of associated
      problems in students. 

PMID- 26221816
TI  - [Interprofessional collaboration in the Family Health Strategy: implications for
      the provision of care and work management].
AB  - Interprofessional collaboration is seen as a resource for tackling model of care
      and workforce problems. The scope of this study was to understand the perception
      about the shared work and interprofessional collaboration of professionals who
      work in primary health care. A qualitative study was conducted in Sao Paulo city.
      In-depth interviews were performed with professionals from distinct categories
      who worked in the Family Health Strategy and Support Center for Family Health.
      The results highlighted the empirical 'professional interaction' and 'production
      goals' categories. The forms of interaction, the role of specialized matrix
      support and the perspective in which production goals are perceived by the
      professionals pointed to tensions between traditional professional logic and
      collaboration logic. It also revealed the tensions between a model based on
      specialized procedures and a more collaborative model centered on health needs of
      families and of the community. The sharing of responsibilities and practices,
      changes in the logic of patient referral to specialized services and inadequate
      organizational arrangements remain major challenges to the integration of
      interprofessional collaboration for the development of new care practices.

PMID- 26221817
TI  - [Sexual and reproductive rights during adolescence: UN-Brazil interactions].
AB  - The scope of this article is to describe the international documents of the UN
      and laws passed in Brazil from 1950 onwards focusing on sexual and reproductive
      rights during adolescence. It involved a descriptive study by consulting the
      official website of the UN organ entitled the Economic Commission for Latin
      America and the Caribbean and sites of the President of the Republic, Ministry of
      Health and Education and the Virtual Health Library. The documents were organized
      from 1950 to 2010 with an emphasis on sexual and reproductive rights and
      adolescence. Ten conferences were found within the scope of the UN: six
      conferences on Population and Development, two on Human Rights, one on the Rights
      of the Child and another on the Millennium Development Goals. Thirty-two
      documents were found in the field of national legislation (four decrees, thirteen
      federal laws, three technical norms, two ordinances, three resolutions, a
      technical note and six programs). The role of the UN and Brazil in consolidating
      the broad concept of sexual and reproductive rights has made significant
      progress, however greater achievements in the area of reproductive rights still
      prevail.

PMID- 26221818
TI  - [Patterns of access to information on protection against UV during the Brazilian
      summer: is there such a thing as the "summer effect"?].
AB  - Internet search patterns associated with "windows" of collective interest have
      been increasingly investigated in the field of public health. This article sets
      out to identify search patterns relating to the quest for information on skin
      protection after the perception of excessive exposure to UV radiation - the so
      called "summer effect" as it is commonly referred to in Brazil. To calculate the
      number of hits on the Brazilian National Cancer Institute website - a renowned
      source of information resources on prevention - log analyzer software was used to
      measure the volume of hits on specific content pages. The pages on skin
      protection and self-examination (pages of interest) were monitored over a 48
      month period. It was seen that, although the monthly average of hits on pages of
      interest revealed statistically significant annual growth, the results for the
      analysis of variance showed no significant differences between the number of hits
      in the summer compared with other months (p = 0.7491). In short, the perception
      of intense exposure to the summer sun did not encourage further interest to
      search for information on prevention.

PMID- 26221819
TI  - Social Inequalities and the Oral health in Brazilian Capitals.
AB  - Despite the improvement of the lives of Brazilians, still persists a panorama of
      iniquities in health in Brazil. This ecological study evaluated the relationship
      of socioeconomic conditions and public health policy with oral health conditions
      in Brazilian capitals. Factor analysis was performed with the socioeconomic
      indicators, revealing two common factors: economic deprivation and socio-sanitary
      condition. Then, was executed multiple linear regression analysis for the oral
      health indicators (average DMFT 12 years, mean missing teeth and rate of decay of
      free population) with two factors in common and fluoridation of water supply.
      Multiple linear regression analysis to the DMFT of the capitals was estimated by
      the socio-sanitary conditions and fluoridation, adjusted by economic deprivation;
      whereas the model for the average missing teeth was estimated only for flu
      oridation and economic deprivation, and finally, the model for the rate of caries
      free population in the Brazilian capitals was estimated by economic and
      sociosanitary condition set by fluoridated water supplies. Therefore, the results
      indicate the need for social actions that impact on people's living conditions to
      reduce tooth decay.

PMID- 26221820
TI  - The inclusion of disabled persons in the labor market in Belo horizonte, Brazil:
      scenario and perspective.
AB  - Even after the publication of Law 8213 in 1991, which established quotas for
      employing disabled persons, their inclusion in the workplace still presents a
      challenge for Brazilian society. In order to understand the main barriers that
      hamper this process a qualitative research study was conducted in the
      municipality of Belo Horizon-te. This study included interviews with important
      actors involved in the process of inclusion; and focus groups including disabled
      persons and members of their families. The main barriers encountered were:
      preconceived ideas and discrimination; family relationships; the Continuous Cash
      Benefit (BPC) program; the low level of qualifi-cation among disabled person;
      lack of access; and the unpreparedness of companies. It was concluded that
      drafting laws is not sufficient to guarantee inclusion in the labor market and
      that governments should implement public policies to assist in this process. 

PMID- 26221821
TI  - [Social representations of municipal health counselors on health surveillance].
AB  - The objective of this study is to describe and analyze the social representations
      of the Health Counselors of the city of Belo Horizonte regarding their
      experiences with health surveillance. The research used the interview technique
      based on a semi-structured script. The data obtained were analyzed using the
      Collective Subject Discourse technique. It was found that the existing gap
      between health surveillance and the Municipal Health Council is offset by the
      broad spectrum of "hands-on" experience acquired by the counselors. This
      experience assumes greater significance in terms of practical knowledge, directly
      influencing the thinking and know-how of these individuals on the topic. In
      practice, proof of the social appropriation of the importance of health
      surveillance as health action qualifies as an effective model of health care. It
      effectively influences the determinants and conditioning factors of the
      health/sickness process, while simultaneously promoting educational initiatives
      that contribute to raising health awareness.

PMID- 26221822
TI  - Brand names of Portuguese medication: understanding the importance of their
      linguistic structure and regulatory issues.
AB  - Among other regulatory requirements, medicine brands should be composed of single
      names without abbreviations to prevent errors in prescription of medication. The
      purposes of the study were to investigate the compliance of a sam ple of
      Portuguese medicine brand names with Portuguese pharmaceutical regulations. This
      includes identifying their basic linguistic characteristics and comparing these
      features and their frequency of occurrence with benchmark values of the
      colloquial or informal language. A sample of 474 brand names was selected. Names
      were analyzed using manual (visual analyses) and computer methods (FreP -
      Frequency Patterns of Phonological Objects in Portuguese and MS word). A
      significant number of names (61.3%) failed to comply with the Portuguese
      phonologic system (related to the sound of words) and/or the spelling system
      (related to the written form of words) contained more than one word, comprised a
      high proportion of infrequent syllable types or stress patterns and included
      abbreviations. The results suggest that some of the brand names of Portuguese
      medication should be reevaluated, and that regulation on this issue should be
      enforced and updated, taking into consideration specific linguistic and spelling
      codes.

PMID- 26221823
TI  - Fuzzy model approach for estimating time of hospitalization due to cardiovascular
      diseases.
AB  - A fuzzy linguistic model based on the Mamdani method with input variables,
      particulate matter, sulfur dioxide, temperature and wind obtained from CETESB
      with two membership functions each was built to predict the average
      hospitalization time due to cardiovascular diseases related to exposure to air
      pollutants in Sao Jose dos Campos in the State of Sao Paulo in 2009. The output
      variable is the average length of hospitalization obtained from DATASUS with six
      membership functions. The average time given by the model was compared to actual
      data using lags of 0 to 4 days. This model was built using the Matlab v. 7.5
      fuzzy toolbox. Its accuracy was assessed with the ROC curve. Hospitalizations
      with a mean time of 7.9 days (SD = 4.9) were recorded in 1119 cases. The data
      provided revealed a significant correlation with the actual data according to the
      lags of 0 to 4 days. The pollutant that showed the greatest accuracy was sulfur
      dioxide. This model can be used as the basis of a specialized system to assist
      the city health authority in assessing the risk of hospitalizations due to air
      pollutants.

PMID- 26221824
TI  - [Subjectivity, ethics and productivity in post-productive health restructuring].
AB  - The scope of this paper is to analyze the ethical problems generated by the
      modern stressor pattern of post-transformation productivity in productive
      restructuring in the health area. It is a qualitative study of the descriptive
      and exploratory type in which 30 professionals (nurses, doctors and dental
      surgeons) from a metropolitan region in the South of Brazil were interviewed, all
      of whom had prior experience in the public and private sectors. The results were
      analyzed through Discursive Textual Analysis. Capitalization is revealed as a
      major ethical problem in the series of new issues derived from the productivity
      profitability imperative in health, due to the acritical incorporation of ethics
      that is restricted to the company's interests or to corporate-individual
      interests. The ethical problem of low professional commitment to the needs of the
      patient and of the social collective indicates the need to build a new engaged
      solidarity in order to increase the quality of public healthcare. Productivity
      targeted at individual and social needs/interests in the area of health requires
      a new self-managing and collective engagement of the subjects, supported by an
      institutional and ethical-political effort of group action, cooperation and
      solidarity.

PMID- 26221826
TI  - Correction: Divorce in families of children with Down Syndrome or Rett Syndrome.

PMID- 26221827
TI  - Correction: Exploring Mexican adolescents' perceptions of environmental health
      risks: a photographic approach to risk analysis.

PMID- 26221828
TI  - Correction: Vulnerability synthetic indices: a literature integrative review.

PMID- 26221829
TI  - Pharmacological approaches to the study of social behaviour.

PMID- 26221830
TI  - Affective communication in rodents: serotonin and its modulating role in
      ultrasonic vocalizations.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is an important modulatory neurotransmitter
      and functions as a key neurodevelopmental signal in the mammalian brain. 5-HT
      plays a prominent role in regulating various types of psychological processes and
      functions, including mood and emotion, particularly anxiety, but also in
      regulating social behavior. Consequently, the 5-HT system is implicated in
      various neuropsychiatric disorders, such as anxiety disorders and depression or
      autism spectrum disorders (ASD), with selective 5-HT reuptake inhibitors being
      the frontline medication. Mice and rats perceive and emit ultrasonic
      vocalizations (USV). It is widely believed that the various distinct USV types
      reflect the animal's affective state, such as anxiety or pleasure. Furthermore,
      they serve communicative functions, for instance, as alarm calls or social
      contact calls. Manipulations targeting the 5-HT system alter affective ultrasonic
      communication in rodents throughout life, probably because of its important role
      in regulating anxiety and social behavior. Ample evidence indicates the
      involvement of the 5-HT system in modulating isolation-induced USV in pups. Later
      in life, the 5-HT system plays a strong modulatory role in the emission of
      aversive 22-kHz USV in rats. So far, little is known about the role of 5-HT in
      the production of interaction-induced USV in mice and appetitive 50-kHz USV in
      rats, although recent findings also suggest a modulatory effect of the 5-HT
      system. Assessment of rodent USV is a valuable method to investigate mood and
      emotion, and to enhance our understanding of, and develop novel pharmacological
      therapies for neuropsychiatric disorders, such as anxiety disorders and
      depression or ASD. 

PMID- 26221831
TI  - Effect of drugs of abuse on social behaviour: a review of animal models.
AB  - Social behaviour is disturbed in many substance abuse and psychiatric disorders.
      Given the consensus that social behaviours of lower mammals may help to
      understand some human emotional reactions, the aim of the present work was to
      provide an up-to-date review of studies on the changes in social behaviour
      induced by drugs of abuse. Various animal models have been used to study the
      relationship between drugs of abuse and social behaviour. Herein, we describe the
      effects of different substances of abuse on the three most commonly used animal
      models of social behaviour: the social play test, the social interaction test and
      the resident-intruder paradigm. The first is the most widely used test to assess
      adolescent behaviour in rodents, the second is generally used to evaluate a wide
      repertoire of behaviours in adulthood and the latter is specific to aggressive
      behaviour. Throughout the review we will explore the most relevant studies
      carried out to date to evaluate the effects of alcohol, cocaine, opioids, 3,4
      methylenedioxymethamphetamine (MDMA), cannabinoids, nicotine and other drugs of
      abuse on these three paradigms, taking into account the influence of different
      variables, such as social history, age and type of exposure. Drugs of diverse
      pharmacological classes induce alterations in social behaviour, although they can
      be contrasting depending on several factors (drug, individual differences and
      environmental conditions). Ethanol and nicotine increase social interaction at
      low doses but reduce it at high doses. Psychostimulants, MDMA and cannabinoids
      reduce social interaction, whereas opiates increase it. Ethanol and
      psychostimulants enhance aggression, whereas MDMA, opiates, cannabinoids and
      nicotine reduce it. Prenatal drug exposure alters social behaviour, whereas drug
      withdrawal decreases sociability and enhances aggression. As a whole, this
      evidence has improved our understanding of the social dimension of drug
      addiction. 

PMID- 26221832
TI  - Dyadic social interaction inhibits cocaine-conditioned place preference and the
      associated activation of the accumbens corridor.
AB  - Impaired social interaction is a hallmark symptom of many psychiatric disorders.
      In substance use disorders, impaired social interaction is triply harmful (a)
      because addicts increasingly prefer the drug of abuse to the natural reward of
      drug-free social interaction, thus worsening the progression of the disease by
      increasing their drug consumption, (b) because treatment adherence and,
      consequently, treatment success itself depends on the ability of the recovering
      addict to maintain social interaction and adhere to treatment, and (c) because
      socially interacting with an individual suffering from a substance use disorder
      may be harmful for others. Helping the addict reorient his/her behavior away from
      the drug of abuse toward social interaction would therefore be of considerable
      therapeutic benefit. This article reviews our work on the neural basis of such a
      reorientation from cocaine, as a prototypical drug of abuse, toward dyadic (i.e.
      one-to-one) social interaction and compares our findings with the effects of
      other potentially beneficial interventions, that is, environmental enrichment or
      paired housing, on the activation of the accumbens and other brain regions
      involved in behavior motivated by drugs of abuse or nondrug stimuli. Our
      experimental models are based on the conditioned place preference paradigm. As
      the therapeutically most promising finding, only four 15 min episodes of dyadic
      social interaction were able to inhibit both the subsequent reacquisition/re
      expression of preference for cocaine and the neural activation associated with
      this behavior, that is, an increase in the expression of the immediate early gene
      Early Growth Response protein 1 (EGR1, Zif268) in the nucleus accumbens,
      basolateral and central amygdala, and the ventral tegmental area. The time spent
      in the cocaine-associated conditioning compartment was correlated with the
      density of EGR1-activated neurons not only in the medial core (AcbCm) and medial
      shell (AcbShm) of the nucleus accumbens, but was observed in all regions medial
      to the anterior commissure ('accumbens corridor'), including (from medial to
      lateral), the vertical limb of the diagonal band and the medial septum (VDB+MS),
      the major island of Calleja and the intermediate nucleus of the lateral septum
      (ICjM+LSI), the AcbShm, and the AcbCm. All effects were limited to GABAergic
      projection neurons (called 'medium spiny neurons', in the accumbens),
      encompassing both dopamine D1 receptor-expressing and D2 receptor-expressing
      medium spiny neuron subtypes. Our EGR1 expression findings were mirrored in
      multielectrode array recordings. Finally, we have validated our paradigm in
      C57BL/6 mice to make use of the plethora of transgenic models available in this
      genus.

PMID- 26221834
TI  - 'Land-marks of the universe': John Herschel against the background of positional
      astronomy.
AB  - John Herschel (1792-1871) was the leading British natural philosopher of the
      nineteenth century, widely known and regarded for his work in philosophy, optics
      and chemistry as well as his important research and popular publications on
      astronomy. To date, however, there exists no extended treatment of his
      astronomical career. This paper, part of a larger study exploring Herschel's
      contributions to astronomy, examines his work in the context of positional
      astronomy, the dominant form of astronomical practice throughout his lifetime.
      Herschel, who did not himself practice positional astronomy and who was known for
      his non-meridional observations of specific stellar objects, was nonetheless a
      strong advocate for positional astronomy-but for very different reasons than the
      terrestrial applications to which it was most often put. For Herschel, the star
      catalogues of positional astronomy were the necessary observational foundation
      upon which information about the stars as physical objects could be constructed.
      Positional astronomy practiced in the great national observatories was not about
      navigation or timekeeping; it was a way to standardize stellar observations and
      make them useful data for constructing theories of the stars themselves. For
      Herschel, the seeds of the new astronomy emerged from the practices of the old. 

PMID- 26221833
TI  - Antipsychotic drugs on maternal behavior in rats.
AB  - Rat maternal behavior is a complex social behavior. Many clinically used
      antipsychotic drugs, including the typical drug haloperidol and the atypical
      drugs clozapine, risperidone, olanzapine, quetiapine, aripiprazole, and
      amisulpride, disrupt active maternal responses (e.g. pup retrieval, pup licking,
      and nest building) to various extents. In this review, I present a summary of
      recent studies on the behavioral effects and neurobiological mechanisms of
      antipsychotic action on maternal behavior in rats. I argue that antipsychotic
      drugs at clinically relevant doses disrupt active maternal responses primarily by
      suppressing maternal motivation. Atypical drug-induced sedation also contributes
      to their disruptive effects, especially that on pup nursing. Among many potential
      receptor mechanisms, dopamine D2 receptors and serotonin 5-HT2A/2C receptors are
      shown to be critically involved in the mediation of the maternal disruptive
      effects of antipsychotic drugs, with D2 receptors contributing more to typical
      antipsychotic-induced disruptions, whereas 5-HT2A/2C receptors contributing more
      to atypical drug-induced disruptions. The nucleus accumbens shell-related reward
      circuitry is an essential neural network in the mediation of the behavioral
      effects of antipsychotic drugs on maternal behavior. This research not only helps
      understand the extent and mechanisms of impact of antipsychotic medications on
      human maternal care, but is also important for enhancing our understanding of the
      neurochemical basis of maternal behavior. It is also valuable for understanding
      the complete spectrum of therapeutic effects and side-effects of antipsychotic
      treatment. This knowledge may facilitate the development of effective intervening
      strategies to help patients coping with such undesirable effects. 

PMID- 26221835
TI  - John Tyndall and the Early History of Diamagnetism.
AB  - John Tyndall, Irish-born natural philosopher, completed his PhD at the University
      of Marburg in 1850 while starting his first substantial period of research into
      the phenomenon of diamagnetism. This paper provides a detailed analysis and
      evaluation of his contribution to the understanding of magnetism and of the
      impact of this work on establishing his own career and reputation; it was
      instrumental in his election as a Fellow of the Royal Society in 1852 and as
      Professor of Natural Philosophy at the Royal Institution in 1853. Tyndall's
      interactions and relationships with Michael Faraday, William Thomson, Julius
      Plucker and others are explored, alongside his contributions to experimental
      practice and to emerging theory. Tyndall's approach, challenging Faraday's
      developing field theory with a model of diamagnetic polarity and the effect of
      magnetic forces acting in couples, was based on his belief in the importance of
      underlying molecular structure, an idea which suffused his later work, for
      example in relation to the study of glaciers and to the interaction of substances
      with radiant heat. 

PMID- 26221836
TI  - Chemistry, microscopy and smell: bloodstains and nineteenth-century legal
      medicine.
AB  - This paper analyses the development of three methods for detecting bloodstains
      during the first half of the nineteenth-century in France. After dealing with the
      main problems in detecting bloodstains, the paper describes the chemical tests
      introduced in the mid-1820s. Then the first uses of the microscope in the
      detection of bloodstains around 1827 are discussed. The most controversial method
      is then examined, the smell test introduced by Jean-Pierre Barruel in 1829, and
      the debates which took place in French academies and learned societies during
      ensuing years are surveyed. Moving to the courtrooms a review is conducted of how
      the different methods were employed in criminal trials. By reviewing these cases,
      the main arguments against Barruel's test during the 1830s are explored as well
      as the changes making possible the return of the microscope to legal medicine
      around 1840. By reconstructing the history of these three methods, the paper
      reveals how the senses of smell and vision (colours and microscopic images) were
      employed in order to produce convincing evidence in both academies and courts.
      The paper questions two linear master narratives that are organized in terms of
      progress and decline: the development of forensic science as a result of
      continued technological progress; and the supposed decline of smell in the
      history of the senses, particularly in the realm of chemistry and medicine. 

PMID- 26221837
TI  - Leibniz's Observations on Hydrology: An Unpublished Letter on the Great Lombardy
      Flood of 1705.
AB  - Although the historical reputation of Gottfried Wilhelm Leibniz (1646-1716)
      largely rests on his philosophical and mathematical work, it is widely known that
      he made important contributions to many of the emerging but still inchoate
      branches of natural science of his day. Among the many scientific papers Leibniz
      published during his lifetime are ones on the nascent science we now know as
      hydrology. While Leibniz's other scientific work has become of increasing
      interest to scholars in recent years, his thinking about hydrology has been
      neglected, despite being relatively broad in extent, including as it does papers
      on the 'raising of vapours' and the formation of ice, as well as the separation
      of salt and fresh water. That list can now be extended still further following
      the discovery of a previously unpublished letter of Leibniz's on the causes of
      the devastating Lombardy flood of October and November 1705. This letter, which
      will be the focus of our paper, reveals the depth of Leibniz's understanding of
      key hydrological processes. In it, he considers various mechanisms for the flood,
      such as heavy rains on high ground, underwater earthquakes, and a mountain
      collapse. Over the course of the paper we examine each of these mechanisms in
      depth, and show that Leibniz was in the vanguard of hydrological thinking. We
      also show that the letter contains one of the first scholarly attempts to apply
      aspects of the still-forming notion of the hydrological cycle to account for a
      flood event. 

PMID- 26221838
TI  - Clinical features of venous insufficiency and the risk of venous thrombosis in
      older people.
AB  - Venous thrombosis is common in older age, with an incidence of 0.5-1% per year in
      those aged >70 years. Stasis of blood flow is an important contributor to the
      development of thrombosis and may be due to venous insufficiency in the legs. The
      risk of thrombosis associated with clinical features of venous insufficiency,
      i.e., varicose veins, leg ulcers and leg oedema, obtained with a standardized
      interview was assessed in the Age and Thrombosis Acquired and Genetic risk
      factors in the Elderly (AT-AGE) study. The AT-AGE study is a case-control study
      in individuals aged 70 years and older (401 cases with a first-time venous
      thrombosis and 431 control subjects). We calculated odds ratios (ORs) and
      corresponding 95% confidence intervals (CI) adjusted for age, sex and study
      centre. Varicose veins and leg ulcer were associated with a 1.6-fold (95% CI 1.2
      2.3) and 3.3-fold increased risk of thrombosis (95% CI 1.6-6.7), respectively,
      while the risk was increased 3.0-fold (95% CI 2.1-4.5) in the presence of leg
      oedema. The risk of thrombosis was highest when all three risk factors occurred
      simultaneously (OR: 10.5; 95% CI 1.3-86.1). In conclusion, clinical features of
      venous insufficiency, i.e., varicose veins, leg ulcers and leg oedema, are risk
      factors for venous thrombosis in older people.

PMID- 26221839
TI  - Protein nanoparticles for therapeutic protein delivery.
AB  - Therapeutic proteins can face substantial challenges to their activity, requiring
      protein modification or use of a delivery vehicle. Nanoparticles can
      significantly enhance delivery of encapsulated cargo, but traditional small
      molecule carriers have some limitations in their use for protein delivery.
      Nanoparticles made from protein have been proposed as alternative carriers and
      have benefits specific to therapeutic protein delivery. This review describes
      protein nanoparticles made by self-assembly, including protein cages, protein
      polymers, and charged or amphipathic peptides, and by desolvation. It presents
      particle fabrication and delivery characterization for a variety of therapeutic
      and model proteins, as well as comparison of the features of different protein
      nanoparticles. 

PMID- 26221840
TI  - Development of silica-containing redox nanoparticles for medical applications.
AB  - Silica-containing redox nanoparticles (siRNP) are nanocomposites consisting of
      silica nanoparticles and amphiphilic block copolymers with nitroxide radicals as
      reactive oxygen species (ROS) scavengers. Electrostatic interactions between the
      cationic segment of a polymer in the core and the entrapped silica nanoparticles
      form a crosslinking structure that provides siRNP stability in vivo, even under
      harsh conditions in the gastrointestinal tract. Due to the adsorption character
      of silica nanoparticles in the nanocomposite, siRNP can be applied not only for
      adsorbents of body wastes but also for drug carriers with high loading capacity.
      The ROS-scavenging character of siRNP significantly improves their performance
      for medical applications. Here, we describe the development of siRNP and provide
      two examples of their medical applications as (1) novel nano-sized adsorbents for
      peritoneal dialysis, and (2) orally administrable drug carriers for the treatment
      of gastrointestinal inflammation. 

PMID- 26221841
TI  - Electrochemical detection of single E. coli bacteria labeled with silver
      nanoparticles.
AB  - A proof-of-concept for the electrochemical detection of single Escherichia coli
      bacteria decorated with silver nanoparticles is reported. Impacts of bacteria
      with an electrode - held at a suitably oxidizing potential - lead to an
      accompanying burst of current with each collision event. The frequency of impacts
      scales with the concentration of bacteria and the charge indicates the extent of
      decoration. 

PMID- 26221843
TI  - Noninvasive theranostic imaging of HSV-TK/GCV suicide gene therapy in liver
      cancer by folate-targeted quantum dot-based liposomes.
AB  - Theranostics is emerging as a popular strategy for cancer therapy; thanks to the
      development of nanotechnology. In this work, we have combined an HSV-TK/GCV
      suicide gene system and near-infrared quantum dots, as the former is quite
      effective in liver cancer treatment and the latter facilitates tumor imaging. A
      folate-modified theranostic liposome (FL/QD-TK) was developed, which is composed
      of an HSV-TK suicide gene covalently coupling with near-infrared fluorescent
      CdSeTe/ZnS core/shell quantum dots. The liver cancer-targeting and biosafety of
      FL/QD-TK were studied in vitro and in vivo. FL/QD-TK exhibited highly specific
      tumor imaging and strong inhibition of the folate receptor-overexpressed Bel-7402
      mouse xenografts without systematic toxicity. This study may shed light on gene
      delivery and targeted cancer therapy. 

PMID- 26221842
TI  - In vitro model alveoli from photodegradable microsphere templates.
AB  - Recreating the 3D cyst-like architecture of the alveolar epithelium in vitro has
      been challenging to achieve in a controlled fashion with primary lung epithelial
      cells. Here, we demonstrate model alveoli formed within a tunable synthetic
      biomaterial platform using photodegradable microspheres as templates to create
      physiologically relevant, cyst structures. Poly(ethylene glycol) (PEG)-based
      hydrogels were polymerized in suspension to form microspheres on the order of 120
      MUm in diameter. The gel chemistry was designed to allow erosion of the
      microspheres with cytocompatible light doses (<=15 min exposure to 10 mW cm(-2)
      of 365 nm light) via cleavage of a photolabile nitrobenzyl ether crosslinker.
      Epithelial cells were incubated with intact microspheres, modified with adhesive
      peptide sequences to facilitate cellular attachment to and proliferation on the
      surface. A tumor-derived alveolar epithelial cell line, A549, completely covered
      the microspheres after only 24 hours, whereas primary mouse alveolar epithelial
      type II (ATII) cells took ~3 days. The cell-laden microsphere structures were
      embedded within a second hydrogel formulation at user defined densities; the
      microsphere templates were subsequently removed with light to render hollow
      epithelial cysts that were cultured for an additional 6 days. The resulting
      primary cysts stained positive for cell-cell junction proteins (beta-catenin and
      ZO-1), indicating the formation of a functional epithelial layer. Typically,
      primary ATII cells differentiated in culture to the alveolar epithelial type I
      (ATI) phenotype; however, each cyst contained ~1-5 cells that stained positive
      for an ATII marker (surfactant protein C), which is consistent with ATII cell
      numbers in native mouse alveoli. This biomaterial-templated alveoli culture
      system should be useful for future experiments to study lung development and
      disease progression, and is ideally suited for co-culture experiments where
      pulmonary fibroblasts or endothelial cells could be presented in the hydrogel
      surrounding the epithelial cysts. 

PMID- 26221845
TI  - Graphene film doped with silver nanoparticles: self-assembly formation,
      structural characterizations, antibacterial ability, and biocompatibility.
AB  - Graphene and silver nanoparticles (AgNPs) are important building blocks for the
      synthesis of functional nanomaterials for bio-related applications. Here, we
      report a facile strategy to decorate AgNPs onto reduced graphene oxide (RGO) by
      the simultaneous reduction of silver ions and graphene oxide nanosheets within
      one system, and further to fabricate a dimension-adjustable RGO/AgNP multi
      layered film by a thermal-driven self-assembly process. The structures of the
      fabricated RGO/AgNP hybrid films were identified by UV-visible spectroscopy, X
      ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy, and
      transmission electron microscopy. The thickness of the fabricated RGO/AgNP film
      was further measured by scanning electron microscopy. The hydrophilicity of the
      RGO/AgNP films was tested by contact angle measurement. Antibacterial and cell
      culture experiments based on the fabricated RGO/AgNP films indicate that this
      kind of hybrid film exhibits excellent antibacterial activity and high
      biocompatibility. A potential antibacterial mechanism of the fabricated RGO/AgNP
      hybrid film was proposed. 

PMID- 26221844
TI  - Surfaces presenting alpha-phenyl mannoside derivatives enable formation of
      stable, high coverage, non-pathogenic Escherichia coli biofilms against pathogen
      colonization.
AB  - Prevention of pathogenic colonization on medical devices over a long period of
      time remains a great challenge, especially in a high-nutrient environment that
      accelerates the production of biomass leading to biofouling of the device. Since
      biofouling and the subsequent pathogen colonization is eventually inevitable, a
      new strategy using non-pathogenic bacteria as living guards against pathogenic
      colonization on medical devices has attracted increasing interest. Crucial to the
      success of this strategy is to pre-establish a high coverage and stable biofilm
      of benign bacteria on the surface. Silicone elastomers are one of the most widely
      used materials in biomedical devices. In this work, we modified silicone surfaces
      to promote formation of high coverage and stable biofilms by a non-pathogenic
      Escherichia coli strain 83972 with type 1 fimbriae (fim+) to interfere with the
      colonization of an aggressive biofilm-forming, uropathogenic Enterococcus
      faecalis. Although it is well known that mannoside surfaces promote the initial
      adherence of fim+ E. coli through binding to the FimH receptor at the tip of the
      type 1 fimbriae, it is not clear whether the fast initial adherence could lead to
      a high coverage and stable protective biofilm. To explore the role of mannoside
      ligands, we synthesized a series of alkyl and aryl mannosides varied in the
      structure and immobilized them on silicone surfaces pre-coated with a
      poly(amidoamine) (PAMAM) dendrimer. We found that stable and densely packed
      benign E. coli biofilms were formed on the surfaces presenting biphenyl mannoside
      with the highest initial adherence of fim+ E. coli. These non-pathogenic biofilms
      prevented the colonization of E. faecalis for 11 days at a high concentration
      (10(8) CFU mL(-1), 100,000 times above the diagnostic threshold for urinary tract
      infection) in the nutrient-rich Lysogeny Broth (LB) media. The result shows a
      correlation among the initial adherence of fim+ E. coli 83972, the coverage and
      long-term stability of the resulting biofilms, as well as their efficiency for
      preventing the pathogen colonization.

PMID- 26221846
TI  - A drug formulation using an alginate hydrogel matrix for efficient oral delivery
      of the manganese porphyrin-based superoxide dismutase mimic.
AB  - In order for patients to avail of the therapeutic benefits of antioxidant drugs
      efficiently and conveniently, a robust oral delivery system needs to be
      developed. However, a common problem in oral drug delivery is ensuring that the
      drug remains functionally intact even after it has passed through the acidic
      environment of the gastrointestinal (GI) tract. To protect drugs within the GI
      environment, we formulated a design based on encapsulating liposomal drugs by
      using an alginate matrix as a carrier. The liposomal drug was composed of
      manganese porphyrin (Mn-por), which has been developed as a mimic of superoxide
      dismutase (SOD), as the therapeutic agent based on the antioxidative effect,
      namely superoxide (O2(-)) inhibitory activity. A cytochrome c assay revealed that
      the O2(-) inhibitory activity of Mn-por could be maintained even after treatment
      with simulated gastric and intestinal fluids. We demonstrated that oral
      administration of the formulated drug significantly inhibited the growth of
      transplanted tumors in mice. The drug formulation presented in this study would
      be a good candidate for orally available systems, which can effectively deliver
      SOD mimics. 

PMID- 26221847
TI  - Hyperbranched PEG-based supramolecular nanoparticles for acid-responsive targeted
      drug delivery.
AB  - Herein, hyperbranched poly(ethylene glycol)-based supramolecular nanoparticles
      with pH-sensitive properties were designed and used for targeted drug delivery.
      Via host-guest recognition between benzimidazole anchored poly(ethylene glycol)
      hyperbranched polyglycerol (PEG-HPG-BM) and folic acid modified CD (FA-CD),
      targeted supramolecular nanoparticles (TSNs) were fabricated. At neutral aqueous
      conditions TSNs could load the model drug DOX. While under intracellular acidic
      conditions the loaded-drug would be released due to the protonation of BM. This
      protonation allowed the supramolecular nanoparticles to expand or even
      disassemble, which showes the pH-dependent property. The introduction of the
      active targeting FA molecule and the specific interactions with the receptor of
      HeLa cells means that DOX-loaded TSNs show a significantly improved anticancer
      efficacy. In vitro drug release assays and intracellular experiments confirmed
      that TSNs had an obvious pH-sensitive property and remarkably improved anticancer
      effects, which hold great potential for further biomedical applications such as
      anticancer drug delivery. 

PMID- 26221848
TI  - Bisalkynylated 3,6-diiminocyclohexa-1,4-diene-1,4-diamine.
AB  - Reduction of bis(benzothiadiazol) by LiAlH4/CuI gives diethynylated
      diaminobenzoquinoneimine. This building block accesses novel targets in a one
      step condensation reaction with different ortho-quinones, resulting in unexpected
      rearrangement products. The compounds are characterized by their photophysical
      and electrochemical data as well as quantum chemical calculations. 

PMID- 26221850
TI  - A Crossover Reconstruction Between the Forehead Expansion and Upper Eyelid Skin.
AB  - BACKGROUND: In cosmetic surgery, the authors have successfully used forehead
      expansion for reconstruction of the upper eyelid, and have found it to be
      indispensable for reconstruction of the upper eyelid. In such an operation,
      preserving the eyebrow is often a problem, and they suggest an approach in 2
      stages, which allows us to both save the eyebrow and use the expander flap at the
      same time. In the last 6 years, they have performed 5 forehead expansions for
      total upper eyelid skin reconstruction, achieving very good aesthetic outcomes.
      METHODS: Firstly, the authors measure the defect and choose an appropriate
      expander implant for the forehead. Secondly, they cut out the pathologically
      changed-turned red or scarred-skin to protect the eyebrow. Next they get out the
      tissue expander and use the tissue flap to repair the upper eyelid defect, while
      the eyebrow is under the expander flap, covered by skin, which they originally
      cut from the upper eyelid. Three weeks later they can cut down the pedicel and
      the flap becomes the new upper eyelid skin. RESULTS: The authors find that the
      new upper eyelid skin may be vascularized by dermatological vessels from the
      expander flap. The forehead expander flap is reliable and particularly well
      suited for an upper eyelid, with numerous advantages. In this way, they make
      maximal use of the expander flap and no additional incision is needed. LEVEL OF
      EVIDENCE: Level IV, therapeutic study.

PMID- 26221851
TI  - Individualized Surgical Templates and Titanium Microplates for Le Fort I
      Osteotomy by Computer-Aided Design and Computer-Aided Manufacturing.
AB  - The authors report the use of novel individualized surgical templates and
      titanium miniplates for Le Fort I osteotomy and evaluate the accuracy of this
      technique in vitro. Nine three-dimensional stereolithographic skull models were
      used to design the templates and titanium microplates and to simulate the
      operation. Cone beam computed tomography (CBCT) scans of the skulls were acquired
      preoperatively and were used to generate virtual models. The surgical plans were
      made based on three-dimensional cephalometric analyses, and osteotomies were then
      performed virtually. Cylinder-shaped markers were placed to permit the correct
      location of titanium screws, and individualized surgical templates were designed.
      The bony segments were then repositioned virtually according to the surgical
      plans to correct the skeletal deformities. Resin surgical templates were produced
      by stereolithography rapid prototyping and the titanium miniplates by three
      dimensional cutting. Le Fort I osteotomy was performed under the guide of the
      surgical templates and fixed with the titanium miniplates. Postoperatively, CBCT
      scans of each skull model were taken, and the differences between the actual and
      planned surgical outcomes were measured by superimposing the planned and
      postoperative virtual models generated from CBCT images. The authors demonstrated
      that the average linear difference between the planned and actual outcomes was <1
      mm and the average orientation difference was <1 degrees . The individualized
      surgical templates and titanium microplates designed in this experimental study
      permitted the repositioning of the maxillary segment to the correct planned
      positions during Le Fort I osteotomy, making this technique a promising
      alternative to the conventional split method. 

PMID- 26221852
TI  - Temporomandibular-External Auditory Canal Fistulas Treatment: Patient With Air
      Into the Synovial Compartment.

PMID- 26221853
TI  - Use of Pedicled Trapezius Myocutaneous Flap for Posterior Skull Reconstruction.
AB  - BACKGROUND: Soft-tissue defects in posterior skull can be challenging for
      reconstruction. If related to tumor resection, these wound beds are generally
      irradiated and can be difficult from a recipient-vessel perspective for a free
      tissue transfer. Locoregional flaps might prove to be important reconstructive
      option in such patients. There is a very limited data on the usage of pedicled
      trapezius myocutaneous flaps for such defects. METHODS: The authors reviewed
      existing study for usage of trapezius flap for posterior skull repair and used
      pedicled trapezius myocutaneous flaps based on the descending branch of
      superficial cervical artery (SCA) for reconstruction of posterior skull soft
      tissue defect in an irradiated and infected wound. RESULTS: Two patients were
      operated for trapezius myocutaneous flap for posterior skull defects complicated
      by cerebrospinal fluid (CSF) leakage and epidural abscess. There was no recipient
      or donor-site complication at a mean follow-up of 12.5 months. Neither of the 2
      patients had any functional deficits for the entire duration of the follow-up.
      Although this flap was able to help in controlling the CSF leakage in the first
      patient, it successfully healed the cavity generated from epidural abscess
      drainage in the second patient. CONCLUSION: The large angle of rotation coupled
      with the ability to complete the procedure without repositioning the patients
      makes trapezius myocutaneous flap an attractive option for posterior skull
      reconstruction. In our limited experience, the pedicled trapezius flaps are a
      reliable alternative as they are well vascularized and able to obliterate the
      soft-tissue defect completely. The recipient site healed completely in infected
      as well as irradiated wound beds. In addition, the donor site can be primarily
      closed with minimal donor-associated complication.

PMID- 26221854
TI  - Concomitant Idiopathic Orbital Inflammatory Pseudotumor and Thyroid-Associated
      Ophthalmopathy.
AB  - PURPOSE: Coexistence of idiopathic orbital inflammatory pseudotumor (IOIP) and
      thyroid-associated ophthalmopathy (TAO) is extremely rare. The purpose of this
      article is to analyze the clinical features, image findings, and therapeutic
      outcomes of concomitant IOIP and TAO in China. MATERIALS AND METHODS: Detailed
      clinical records of 3 Chinese patients with concomitant IOIP and TAO were
      reviewed, including their clinical history, symptoms and signs, ultrasonography,
      computed tomography (CT), and steroid therapy. RESULTS: Among the 3 patients,
      were 2 men and 1 woman, aged 42, 49, and 48 years, respectively. The right orbit
      was involved in 1 patient and both orbits in 2 patients. In addition to showing
      the typical features of TAO, such as hyperthyroidism, upper eyelid retraction,
      and enlarged extraocular muscles with tendon sparing, all 3 patients showed
      ambiguous soft tissue masses in one or both orbits. Pathologic examination after
      biopsy of the mass in 1 patient confirmed the diagnosis of lymphatic IOIP. All
      the patients responded extremely well to steroid treatment. CONCLUSIONS: Although
      rare, a simultaneous coexistence of IOIP and TAO can occur. Therefore, it is
      important for clinicians to be aware of the potential for concomitant IOIP and
      TAO.

PMID- 26221855
TI  - Improved Construction of Auricular Prosthesis by Digital Technologies.
AB  - Implant-retained auricular prostheses are a successful prosthetic treatment
      option for patients who are missing their ear(s) due to trauma, oncology, or
      birth defects. The prosthetic ear is aesthetically pleasing, composed of natural
      looking anatomical contours, shape, and texture along with good color that blends
      with surrounding existing skin. These outcomes can be optimized by the
      integration of digital technologies in the construction process. This report
      describes a sequential process of reconstructing a missing left ear by digital
      technologies. Two implants were planned for placement in the left mastoid region
      utilizing specialist biomedical software (Materialise, Belgium). The implant
      positions were determined underneath the thickest portion (of anti-helix area)
      left ear that is virtually simulated by means of mirror imaging of the right ear.
      A surgical stent recording the implant positions was constructed and used in
      implant fixtures placement. Implants were left for eight weeks, after which they
      were loaded with abutments and an irreversible silicone impression was taken to
      record their positions. The right existing ear was virtually segmented using the
      patient CT scan and then mirror imaged to produce a left ear, which was then
      printed using 3D printer (Z Corp, USA). The left ear was then duplicated in wax
      which was fitted over the defect side. Then, it was conventionally flasked. Skin
      color was digitalized using spectromatch skin color system (London, UK). The
      resultant silicone color was mixed as prescribed and then packed into the mold.
      The silicone was cured conventionally. Ear was trimmed and fitted and there was
      no need for any extrinsic coloring. The prosthetic ear was an exact match to the
      existing right ear in shape, skin color, and orientation due to the great
      advantages of technologies employed. Additionally, these technologies saved time
      and provided a base for reproducible results regardless of operator. 

PMID- 26221856
TI  - Morphological Characteristics of the Sphenoid Sinus and Endoscopic Localization
      of the Cavernous Sinus.
AB  - The aim of this study was to investigate the relationship between the
      morphological characteristics of the sphenoid sinus and endoscopic localization
      of the cavernous sinus (CS) using an extended endoscopic endonasal
      transsphenoidal approach. Thirty sides of CS in 15 adult cadaver heads were
      dissected to simulate the extended endoscopic endonasal transsphenoidal approach,
      and the morphology of the sphenoid sinus and anatomic structures of CS were
      observed. The opticocarotid recess (OCR), ophthalmomaxillary recess (V1V2R), and
      maxillomandibular recess (V2V3R) in the lateral wall of the sphenoid sinus were
      presented in 16 sides (53.3%), 6 sides (20%), and 4 sides (13.3%) of the 30
      sides, respectively. OCR is a constant anatomic landmark in endoscopy and
      coincides with the anterior portion of the clinoidal triangle. The C-shaped
      internal carotid artery (ICA) in the lateral wall of the sphenoid sinus was
      presented in 11 sides (36.7%), the upper one-third of which corresponds to the
      middle portion of the clinoidal triangle, and the lower two-thirds of which
      correlates to the supratrochlear triangle, infratrochlear triangle, and
      ophthalmic nerve in CS, around which the medial, lateral, and anteroinferior
      interspaces are distributed. From a front-to-behind perspective, the C-shaped ICA
      consists of inferior horizontal segment, anterior vertical segment, clinoidal
      segment as well as partial subarachnoid segment of the ICA. OCR and C-shaped ICA
      in the lateral wall of the sphenoid sinus are the 2 reliable anatomic landmarks
      in the intraoperative location of the parasellar region of CS. 

PMID- 26221857
TI  - Cytotoxic Effects of Intranasal Midazolam on Nasal Mucosal Tissue.
AB  - The aim of this experimental study was to investigate the cytotoxic effects of
      intranasal midazolam on nasal mucosal tissue in rats. Forty healthy rats were
      randomly divided into 5 groups. Group 1 (n = 8) was the control group, group 2 (n
      = 8) received intranasal saline, group 3 (n = 8) received intranasal midazolam,
      group 4 (n = 8) received intraperitoneal saline, and group 5 received
      intraperitoneal midazolam (n = 8). Midazolam and saline were administered via
      intraperitoneal and intranasal routes at doses of 200 MUg/kg. Nasal septal
      mucosal stripe tissues were removed at the 6th hour. All materials were evaluated
      according to Ki67 and p53 staining to evaluate proliferation and apoptosis,
      respectively, and hemotoxylin and eosin staining was performed for histopathology
      evaluation. Ki67 values and inflammation in group 3 were statistically higher
      compared to group 1, group 2, and group 4. P53 values in group 3 were
      statistically higher compared to group 1. Assessment of subepithelial edema
      between group 3 and the other groups revealed no statistically significant
      differences. Assessment of cilia loss between group 3 and group 1, group 2, and
      group 4 revealed no statistically significant difference. The evaluation of
      goblet cell loss between group 3 and group 1 revealed a statistically significant
      difference. Intranasal midazolam had adverse effects on nasal mucosa. However,
      intranasal midazolam is as safe as systemic midazolam administration with respect
      to nasal mucosa. 

PMID- 26221858
TI  - Primary Diffuse Large B-Cell Dural Lymphoma With Bone and Subcutaneous Tissue
      Involvement Mimicking Meningioma.
AB  - Primary dural lymphoma (PDL), a rare subtype of primary central nervous system
      lymphoma (PCNSL), is usually a marginal zone B-cell lymphoma or low-grade B-cell
      lymphoma of mucosa-associated lymphoid tissue type. Primary dural invasion by
      diffuse large B-cell lymphoma is extremely rare, with only a few cases reported
      in the literature. The authors presented an unusual case of primary dural
      involvement by a high-grade diffuse large B-cell lymphoma that invaded parietal
      bone and subcutaneous tissue. The patient received tumor complete resection and
      cranioplasty as well as radiotherapy and chemotherapy as adjuvant treatment after
      surgery. During 12 months follow-up, no tumor recurrence was found. Primary dural
      lymphoma should be differentially diagnosed with meningioma. Once the diagnosis
      of PDL is established, tumor resection and adjuvant radiation and chemotherapy
      may obtain relatively good prognosis. 

PMID- 26221859
TI  - The impact of recent hospitalization on surgical site infection after a
      pancreatectomy.
AB  - BACKGROUND: Surgical site infections (SSI) are a major cause of increased
      morbidity and cost after a pancreatectomy. Patients undergoing a pancreatectomy
      frequently have had recent inpatient hospital admissions prior to their surgical
      admission (recent pre-surgical admission, RPSA), which could increase the risk of
      SSI. METHODS: The 2009-2011 Healthcare Cost Utilization Project California State
      Inpatient Database was used. Chi-square tests, Student's t-tests and
      multivariable logistic regression were used. RESULTS: Three thousand three
      hundred and seventy-six patients underwent a pancreatectomy, and 444 (13.2%) had
      RPSA. One hundred and eighty (40.5%) RPSAs were to different hospitals other than
      where patients' pancreatectomy took place. In univariate analysis, patients with
      RPSA had a significantly higher rate of post-operative SSIs, and this was
      associated with a longer length of post-operative stay, higher post-operative
      hospital costs and increased postoperative 30-day readmission rates (Table 1). In
      Multivariate analysis, RPSA was an independent predictor of post-operative SSI
      [odds ratio (OR) = 1.68, P = 0.013], and the risk of SSI increased with
      increasing RPSA length of stay (OR = 1.07 per day, P = 0.001). CONCLUSIONS:
      Recent pre-surgical admission is an important risk factor for SSI after a
      pancreatectomy. Many patients with RPSA are not admitted pre-operatively to the
      same hospital where the pancreatectomy occurs; in such circumstances, SSI rates
      may not be a sole reflection of the care provided by operating hospitals.

PMID- 26221860
TI  - FROM WHENCE THEY CAME--ANTIBIOTIC-RESISTANT ESCHERICHIA COLI IN AFRICAN WILDLIFE.
AB  - The emergence of antimicrobial resistance is arguably the most important threat
      to human and animal health. The impacts of antimicrobial use can reach far from
      the site of prescription and wildlife may serve as a conduit for the movement of
      resistance across landscapes, contributing to the spread of antimicrobial
      resistance within and between different reservoirs. We compared antimicrobial
      resistance and life history among wild and domestic species in Chobe, Botswana to
      explore key attributes and behaviors that may increase exposure and allow
      resistance to move between humans, animals, and ecosystems. Among 150 fecal
      samples evaluated from African animals, 41.3% contained Escherichia coli isolates
      that were resistant to one or two of 10 tested antibiotics, and 13.3% of isolates
      demonstrated multidrug resistance (three or more antibiotics). Resistance to each
      of the 10 tested antibiotics was detected among wildlife fecal samples.
      Resistance was widespread, but not ubiquitous, and isolates from wildlife
      demonstrated similar patterns of resistance to human E. coli from environmental
      and clinical sources in the study area. Multidrug resistance was significantly
      higher in carnivores, water-associated species, and species inhabiting urban
      areas, suggesting that life history may be key to understanding exposure patterns
      and transmission dynamics in heterogeneous landscapes. 

PMID- 26221861
TI  - Mucoepidermoid Carcinoma in Children: A Single Institutional Experience.
AB  - PURPOSE AND OBJECTIVE: To determine the clinicopathologic and molecular features
      and outcome of children with mucoepidermoid carcinoma (MEC). METHODS: A
      retrospective analysis of clinical and histopathologic findings was performed in
      patients with MEC diagnosed at Texas Children's Cancer Center between 2000 and
      2014. RESULTS: Ten female and four male patients with median age 12 years (range
      7-19 years) were included in the study. Tumors involved major salivary glands,
      minor salivary glands of the palate, and the tracheobronchial tree. Nine of 11
      patients with salivary MEC underwent more than one surgical resection at the time
      of initial diagnosis to achieve a gross total resection. Three patients with
      tracheobronchial tumors underwent pulmonary lobectomy. Three patients received
      postoperative radiation therapy. No patient was treated with chemotherapy.
      Histopathologic grades were classified as low (n = 2), intermediate (n = 9), and
      high (n = 3). All 12 patients with tumor tissue available for testing were
      positive for MECT1/MAML2 fusion transcripts. There were no deaths, metastases, or
      recurrences in this series, with a median follow-up of 24 months (range 5-96
      months). CONCLUSIONS: Low to intermediate histopathologic grade MECs are more
      common than high grade MEC in children. In contrast to adults, MECT1/MAML2 fusion
      transcripts occur with a frequency of 100% in our pediatric MEC series. Complete
      excision is the treatment of choice and is associated with excellent outcome. The
      role of radiotherapy is unclear, but may be indicated in patients with high grade
      tumors with positive surgical margins.

PMID- 26221863
TI  - BTEX biodegradation and its nitrogen removal potential by a newly isolated
      Pseudomonas thivervalensis MAH1.
AB  - Benzene, toluene, ethylbenzene, and xylene (BTEX) are of great environmental
      concern because of their widespread occurrence in groundwater and soil, posing an
      increasing threat to human health. The aerobic denitrifying BTEX-degrading
      bacterium Pseudomonas thivervalensis MAH1 was isolated from BTEX-contaminated
      sediment under nitrate-reducing conditions. The degradation rates of benzene,
      toluene, ethylbenzene, and xylene by strain MAH1 were 4.71, 6.59, 5.64, and 2.59
      mg.L-1day-1, respectively. The effects of sodium citrate, nitrate, and NaH2PO4 on
      improving BTEX biodegradation were investigated, and their optimum concentrations
      were 0.5 g.L-1, 100 mg.L-1, and 0.8 mmol.L-1, respectively. Moreover, MAH1, which
      has nirS and nosZ genes, removed ammonium, nitrate, and nitrite at 2.49 mg
      NH(4)(+)-N.L-1.h-1, 1.50 mg NO(3)(-)-N.L-1.h-1, and 0.83 mg NO(2)(-)-N.L-1.h-1,
      respectively. MAH1 could help in mitigating the pollution caused by nitrogen
      amendments for biostimulation. This study highlighted the feasibility of using
      MAH1 for the bioremediation of BTEX-contaminated sites.

PMID- 26221864
TI  - Engineering a novel biosynthetic pathway in Escherichia coli for production of
      renewable ethylene glycol.
AB  - Ethylene glycol (EG) is an important commodity chemical with broad industrial
      applications. It is presently produced from petroleum or natural gas feedstocks
      in processes requiring consumption of significant quantities of non-renewable
      resources. Here, we report a novel pathway for biosynthesis of EG from the
      renewable sugar glucose in metabolically engineered Escherichia coli. Serine-to
      EG conversion was first achieved through a pathway comprising serine
      decarboxylase, ethanolamine oxidase, and glycolaldehyde reductase. Serine
      provision in E. coli was then enhanced by overexpression of the serine
      biosynthesis pathway. The integration of these two parts into the complete EG
      biosynthesis pathway in E. coli allowed for production of 4.1 g/L EG at a
      cumulative yield of 0.14 g-EG/g-glucose, establishing a foundation for a
      promising biotechnology.

PMID- 26221865
TI  - Step-Edge-Guided Nucleation and Growth of Aligned WSe2 on Sapphire via a Layer
      over-Layer Growth Mode.
AB  - Two-dimensional (2D) materials beyond graphene have drawn a lot of attention
      recently. Among the large family of 2D materials, transitional metal
      dichalcogenides (TMDCs), for example, molybdenum disulfides (MoS2) and tungsten
      diselenides (WSe2), have been demonstrated to be good candidates for advanced
      electronics, optoelectronics, and other applications. Growth of large single
      crystalline domains and continuous films of monolayer TMDCs has been achieved
      recently. Usually, these TMDC flakes nucleate randomly on substrates, and their
      orientation cannot be controlled. Nucleation control and orientation control are
      important steps in 2D material growth, because randomly nucleated and orientated
      flakes will form grain boundaries when adjacent flakes merge together, and the
      formation of grain boundaries may degrade mechanical and electrical properties of
      as-grown materials. The use of single crystalline substrates enables the
      alignment of as-grown TMDC flakes via a substrate-flake epitaxial interaction, as
      demonstrated recently. Here we report a step-edge-guided nucleation and growth
      approach for the aligned growth of 2D WSe2 by a chemical vapor deposition method
      using C-plane sapphire as substrates. We found that at temperatures above 950 
      degrees C the growth is strongly guided by the atomic steps on the sapphire
      surface, which leads to the aligned growth of WSe2 along the step edges on the
      sapphire substrate. In addition, such atomic steps facilitate a layer-over-layer
      overlapping process to form few-layer WSe2 structures, which is different from
      the classical layer-by-layer mode for thin-film growth. This work introduces an
      efficient way to achieve oriented growth of 2D WSe2 and adds fresh knowledge on
      the growth mechanism of WSe2 and potentially other 2D materials. 

PMID- 26221866
TI  - Polymer-Coated Hollow Mesoporous Silica Nanoparticles for Triple-Responsive Drug
      Delivery.
AB  - In this study, pH, reduction and light triple-responsive nanocarriers based on
      hollow mesoporous silica nanoparticles (HMSNs) modified with poly(2
      (diethylamino)ethyl methacrylate) (PDEAEMA) were developed via surface-initiated
      atom transfer radical polymerization. Both reduction-cleavable disulfide bond and
      light-cleavable o-nitrobenzyl ester were used as the linkages between HMSNs and
      pH-sensitive PDEAEMA polymer caps. A series of characterization techniques were
      applied to characterize and confirm the structures of the intermediates and final
      nanocarriers. Doxorubicin (DOX) was easily encapsulated into the nanocarriers
      with a high loading capacity, and quickly released in response to the stimuli of
      reducing agent, acid environment or UV light irradiation. In addition, flow
      cytometry analysis, confocal laser scanning microscopy observations and
      cytotoxicity studies indicated that the nanocarriers were efficiently
      internalized by HeLa cancer cells, exhibiting (i) enhanced release of DOX into
      the cytoplasm under external UV light irradiation, (ii) better cytotoxicity
      against HeLa cells, and (iii) superior control over drug delivery and release.
      Thus, the triple-responsive nanocarriers present highly promising potentials as a
      drug delivery platform for cancer therapy. 

PMID- 26221867
TI  - Persistent type II endoleak after EVAR: the predictive value of the AAA thrombus
      volume.
AB  - BACKGROUND: Persistent type II endoleaks (ELIIp, >=6 months) after an
      endovascular aneurysm repair (EVAR) can be associated with adverse outcomes. The
      aims of this study are the evaluation of the incidence of ELIIp, their
      preoperative morphological predictive features (PMF) and the post-EVAR abdominal
      aortic aneurysm (AAA) evolution in the presence of ELIIp. METHODS: Patients
      underwent EVAR between 2008 and 2010 were prospectively collected. Cases with
      ELIIp (group A: AG) were identified. A control group without ELIIp (group B: BG),
      homogeneous for clinical characteristics, follow-up timing and methods (CTA
      and/or CEUS at 6.12 months and yearly thereafter) was retrospectively selected.
      The PMF evaluated by computed-tomography-angiography (CTA) were: AAA-diameter,
      number and diameter of AAA efferent patent vessels (EPV), AAA-total volume (TV),
      AAA-thrombus volume (THV) and TV/THV rate (%VR). Volumes were calculated by the
      dedicated vessels analysis software. AG and BG were compared. The primary
      endpoint was to evaluate the incidence of ELIIp. Secondary endpoints were to
      analyze the relation between PMF and ELIIp and to assess the post-EVAR AAA
      evolution in the presence of ELIIp. RESULTS: Between 2008 and 2010, 200 patients
      underwent EVAR to treat AAA electively. An ELIIp was detected in 35cases (17.5%)
      (AG). Twenty-seven patients (13.5%) were included in BG. An overall of 62
      patients (GA+GB) were analyzed. The mean pre-operative AAA diameter and EPV were
      58+/-11.6 mm and 5.5+/-1.8 mm, respectively. The mean TV and THV were 187+/-111.5
      cc and 82+/-75 cc, respectively. The median %VR was 42.3%. ELIIp was correlated
      to EPV>=6 (chi2, p=.015) and %VR <40% (logistic regression, P=0.032). The mean
      follow-up was 22+/-9 months. Seven (20%) ELIIp spontaneously sealed and 6 (17%)
      required reinterventions (2 conversions to OR). There were not PMF associated to
      ELIIp evolution and AAA growth post-EVAR. CONCLUSIONS: ELIIp is a not rare
      complication and it could require re-interventions. Our data suggest that VEP>=6
      or %VT<40% are risk factors for ELIIp. No PMF was able to predict the ELIIp
      evolution. The relative high rate of re-interventions, could suggest the need of
      adjunctive/preventing primary procedures in patients at high-risk for ELIIp.

PMID- 26221868
TI  - Retrograde type A dissection following hybrid supra-aortic endovascular surgery
      in high-risk patients unfit for conventional open repair.
AB  - BACKGROUND: Hybrid procedures with combined open extra-anatomical supra-aortic
      bypasses and endovascular surgery are less invasive for patients with complex
      aortic arch pathology. The aim of this paper is to report patients who developed
      retrograde type A aortic dissection following initially successful hybrid
      endovascular treatment. METHODS: Retrospective review of prospectively collected
      computerized departmental database. All patients with supra-aortic hybrid
      endovascular surgery and post-procedure retrograde type A dissection were
      identified. Patient demographics, comorbid conditions, perioperative parameters,
      procedural details and post-operative complications were collected. RESULTS: From
      May 2005 to July 2014, 163 patients underwent thoracic aortic endovascular
      procedures at our institution. From the 46 patients who had supra-aortic hybrid
      endovascular repair, six patients (6/46, 13% of all supra-aortic hybrid cases, 3
      males) developed retrograde type A aortic dissection. All were elective cases,
      with 3 chronic dissecting aneurysms and 3 atherosclerotic aneurysms. All had one
      stage hybrid procedures: 2 patients had carotid-carotid bypass grafts, one had
      carotid-carotid-left subclavian bypass graft, and 3 had bypass grafts from
      ascending aorta to innominate artery and left carotid artery. Five patients had
      Cook Zenith thoracic stent-grafts (Cook Medical, Bloomington, IN, USA), and one
      had Medtronic Valiant stent-grafts (Medtronic Vascular Inc, Santa Rosa, CA, USA).
      The retrograde type A dissection occurred with sudden symptoms at day 5, 6, 10,
      20, 105 and 128, respectively. There were 3 immediate fatalities and 2 patients
      treated conservatively deemed unfit for reintervention (one died of pneumonia at
      9 months, and one remained alive at 7 months post-complication). One patient
      underwent successful emergency open surgery and survived. CONCLUSIONS: Supra
      aortic hybrid procedures in treating aortic arch pathology may be at risk of
      developing retrograde type A dissection. This post-operative complication
      inevitably have poor outcome, even with early diagnosis and prompt treatment.

PMID- 26221869
TI  - Study of the Thermodynamics (Thermal and Cl Catalyzed) and Kinetics of the Cis
      and Trans Isomerizations of CF3CF?CHF, CF3CH?CHCF3, and CH3CH?CHCH3 in 100-950
      Torr of N2 Diluent at 296-875 K: Effect of F and CF3 Substitution on the
      Isomerization Process Including the Fluorine "Cis Effect".
AB  - The equilibrium constants for the Z to E isomerizations of CF3CF?CHF (K1) and
      CF3CH?CHCF3 (K2) have been measured using GC/FID analysis over the temperature
      ranges 360-850 and 297-850 K, respectively. At lower temperature, K was
      determined using Cl atom catalysis. At higher temperature, K was measured without
      a catalyst. The temperature-dependent expressions are K1 (Z to E) = 1.45(+/
      0.15)e(-[2845(+/-100)/RT]) and K2 (Z to E) = 1.9(+/-0.22)e(+[4330(+/-120)/RT])
      (where the gas constant R = 1.986 cal mol(-1) K(-1)). For isomerization 1, the Z
      (fluorine cis) isomer is 2.85 kcal mol(-1) lower in energy than the E (fluorine
      trans) isomer, providing another example of the fluorine "cis effect" in olefins.
      For isomerization 2, the E(trans) isomer is 4.3 kcal mol(-1) lower in energy than
      the corresponding Z(cis) isomer as is normal for olefins. The isomerization rate
      constant in a single direction was also measured for each fluorinated compound: k
      1(E to Z) = 10(13.87+/-0.24)e(-59530(+/-887)/RT) s(-1); and k2(Z to E) =
      10(13.89+/-0.23)e(-58845(+/-675)/RT) s(-1). To verify the experimental method,
      cis to trans (k3) and trans to cis (k-3) isomerization rate constants were also
      measured for cis- and trans-2-butene for comparison to several previous studies.
      The rate constants determined herein are k3 (cis to trans) = 10(13.95+/-0.23)e(
      63245(+/-815)/RT) s(-1); and k-3 (trans to cis) = 10(14.32+/-0.28)e(-64993(+/
      1132)/RT) s(-1). k3 agrees well with four previous measurements and represents
      the best available rate constant for 2-butene. All errors quoted here are 2sigma.
      The typical total pressure for these experiments was 760 +/- 100 Torr. Limited
      experiments performed at 100 Torr showed no pressure dependence for any of the
      compounds above 100 Torr. Thus, all isomerization rate constants represent high
      pressure limits. The rates of the addition reactions of Cl to the double bonds of
      CF3CF?CHF (k4) and CF3CH?CHCF3 (k7) (used in Cl catalysis) were also measured in
      pure N2 and in pure O2. In O2, the rate constants expressions are k4 = 1.56 (+/
      0.22) * 10(-11) e(+(643/RT)) cm3 molecule(-1) s(-1); and k7 = 1.05 * 10(-12)
      e(+(1874/RT)) cm(3) molecule(-1) s(-1). In N2, k4 and k7 decrease several orders
      of magnitude as the temperature increases because of the increasing reversibility
      of the Cl addition reaction, which produces the catalytic effect.

PMID- 26221870
TI  - The Assessment of Hepatosteatosis in Living-Donor Liver Transplant: Comparison of
      Liver Attenuation Index and Histopathologic Results.
AB  - OBJECTIVES: The purpose of the study was to determine the diagnostic value of
      computed tomography densitometry in the quantification of hepatosteatosis.
      MATERIALS AND METHODS: Fifty-one potential liver donors, ranging in age from 19
      to 52 years (mean age: 32.4 years +/- 10.2), participated in the study. The mean
      hepatic attenuation and mean splenic attenuation were determined using regions of
      interest measurements. The difference between the mean hepatic attenuation and
      mean splenic attenuation (or liver attenuation index), with liver attenuation
      index = mean hepatic attenuation - mean splenic attenuation were calculated.
      Computed tomography densitometric parameters were correlated with histopathologic
      results. RESULTS: From the histopathologic analysis, the degree of macrovesicular
      hepatosteatosis was 0% to 8% (mean: 1.1% +/- 2%). Seven donors (13.7%) had a
      degree of macrovesicular steatosis of > 5%, and 12 donors (23.5%) had >= 2%. Of
      the 29 normal donors with histopathologic verification, computed tomography
      densitometry predicted <= 5% of the hepatosteatosis in 27 donors, and <= 2%
      hepatosteatosis in 2 subjects. The liver attenuation index was significantly
      correlated to the histopathologic results. The mathematical relation between
      liver attenuation index and the degree of histopathologic hepatosteatosis was
      calculated using the least-squares methods, which provided quadratic polynomials.
      CONCLUSIONS: Computed tomography densitometry is a rapid, robust, noninvasive
      technique for the assessment of hepatosteatosis. When used in conjunction with
      clinically stable reference measurements of spleen, the density measurements of
      liver correctly predicted the presence of fatty infiltration with significant
      sensitivity (77%) and specificity (75%). This technique, which was refined during
      the course of our liver transplant program, minimizes the need for highly
      invasive percutaneous liver biopsies.

PMID- 26221871
TI  - Immunologic responses to the major allergen of Olea europaea in local and
      systemic allergic rhinitis subjects.
AB  - OBJECTIVE: To evaluate the in vivo and in vitro responses to nOle e 1 in allergic
      rhinitis (AR) and local allergic rhinitis (LAR) patients sensitized to olive tree
      pollen (OL) confirmed by nasal allergen provocation test (NAPT). METHODS: Twelve
      subjects with AR, 12 with LAR and 12 subjects as control group (CG) were
      selected. Skin testing and NAPT with nOle e 1 were performed. Eosinophilic
      cationic protein (ECP) and tryptase were measured in nasal lavages before and
      after NAPT. Serum IgE to OL allergens was measured by ELISA. Basophil activation
      tests (BAT) with OL and nOle e 1 and dendritic cell maturation/proliferation
      studies were carried out. RESULTS: All AR (12/12) and 10/12 (83%) of LAR had a
      +NAPT to nOle e 1. ECP levels in nasal lavages were significantly increased after
      NAPT in both AR and LAR compared with CG at 15 min (P < 0.05). Serum IgE was
      positive only in AR. All AR had +BAT responses to OL and 10/12 to nOle e 1 (83%);
      8/12 LAR (66.6%) had a +BAT to OL and 4/12 (33%) to nOle e 1, with only one
      subject of the CG with a +BAT to both OL and nOle e 1 (8%). Dendritic cell
      proliferation to nOle e 1 was increased in AR compared to LAR and CG (P = 0.019
      and P = 0.001, respectively). CONCLUSION: Both AR and LAR had a similar in vivo
      response to nOle e 1 with release of inflammatory mediators. Specific basophil
      activation with OL and nOle e 1 was observed in LAR confirming previous data
      obtained with dust mites.

PMID- 26221872
TI  - Hepatitis C virus and HIV infections among people who inject drugs in the Middle
      East and North Africa: a neglected public health burden?

PMID- 26221873
TI  - Squalenoylation of Chitosan: A Platform for Drug Delivery?
AB  - The present study describes the synthesis of chitosan-squalene (chitosan-SQ), a
      unique amphiphilic chitosan derivative, which enables the efficient formation of
      nanoparticles in acetate buffer by self-assembly. The influence of different
      parameters on the nanoparticle size such as percentage of substitution, pH of the
      acetate buffer, concentration in chitosan-SQ, and time of stirring was studied.
      It could be demonstrated that this new polymer was nontoxic to cells,
      biodegradable, and preserved the anti-infective properties of the initial
      chitosan.1 Moreover, chitosan-SQ showed good carrier properties by allowing the
      encapsulation of both hydrophilic and hydrophobic model drug compounds. 

PMID- 26221875
TI  - Guanacastane-type diterpenoids from the insect-associated fungus Verticillium
      dahliae.
AB  - Four new guanacastane-type diterpenoids, namely dahlianes A (1), B (2), C (3),
      and D (4), were isolated from cultures of Verticillium dahliae. Their structures
      were elucidated on the basis of extensive spectroscopic data analysis. Their
      absolute configurations were determined by a combination of Mo2(OAc)4-induced
      electronic circular dichroism experiment and Mosher ester method. In cytotoxicity
      evaluation against human tumor cell lines, compounds 2 and 3 exhibited
      significant cytotoxicities against MCF-7 cell lines with IC50 values of 3.35 and
      4.72 MUM, respectively. 

PMID- 26221874
TI  - Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2
      kinase (PFKFB4) inhibitor.
AB  - Human tumors exhibit increased glucose uptake and metabolism as a result of high
      demand for ATP and anabolic substrates and this metabolotype is a negative
      prognostic indicator for survival. Recent studies have demonstrated that cancer
      cells from several tissue origins and genetic backgrounds require the expression
      of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4), a regulatory
      enzyme that synthesizes an allosteric activator of glycolysis, fructose-2,6
      bisphosphate. We report the discovery of a first-in-class PFKFB4 inhibitor, 5-(n
      (8-methoxy-4-quinolyl)amino)pentyl nitrate (5MPN), using structure-based virtual
      computational screening. We find that 5MPN is a selective inhibitor of PFKFB4
      that suppresses the glycolysis and proliferation of multiple human cancer cell
      lines but not non-transformed epithelial cells in vitro. Importantly, 5MPN has
      high oral bioavailability and per os administration of a non-toxic dose of 5MPN
      suppresses the glucose metabolism and growth of tumors in mice.

PMID- 26221876
TI  - Sorafenib combined with percutaneous radiofrequency ablation for the treatment of
      medium-sized hepatocellular carcinoma.

PMID- 26221878
TI  - Feasibility of office CO2 laser surgery in patients affected by benign
      pathologies and congenital malformations of female lower genital tract.
AB  - OBJECTIVE: Traditional surgery presents some disadvantages, such as the necessity
      for general anesthesia, hemorrhage, recurrence of pathology, and the possible
      onset of dyspareunia due to an excessive scarring. CO2 laser surgery might
      resolve these problems and might be employed in a wider range of clinical
      indications than usual. We examined the results of CO2 laser surgery in patients
      affected by benign pathologies and congenital malformations of the female lower
      genital tract. PATIENTS AND METHODS: In this observational study, we enrolled 49
      women who underwent CO2 laser surgery for the following indications: Bartholin's
      gland cyst, imperforate hymen, vaginal septum, Nabothian cyst, and vaginal
      polyps. Feasibility, cost-effectiveness, complication rate, recurrence rate,
      short- and long-term outcomes were assessed. RESULTS: All procedures were carried
      out in a short operative time, without any intraoperative complications. Only 1
      (2.0%) out of 49 patients required a hemostatic suture for bleeding.
      Postoperative period was uneventful in all patients, except 6 (12.2%) out of 49
      patients who reported pain one day after surgery, successfully treated with
      paracetamol. Healing was rapid and excellent in all cases; no wound infection,
      scarring or stenosis were noticed. Preoperative symptoms reduced or disappeared
      in all cases. No recurrence was observed and no re-intervention was needed.
      CONCLUSIONS: CO2 laser surgery provides several advantages over traditional
      surgery, as its systematic use in treating pre-invasive, benign, and congenital
      pathologies of the female lower genital tract reduces patient discomfort,
      improves short- and long-term outcomes, and optimizes cost-effectiveness.

PMID- 26221877
TI  - Treatments of caesarean scar pregnancy and the corresponding results in ten
      years.
AB  - OBJECTIVE: The purpose of this essay is to explore the treatments of caesarean
      scar pregnancy and the corresponding results during the past ten years. PATIENTS
      AND METHODS: There were 56 cases of caesarean scar pregnancy in the past ten
      years which were divided into two groups. Group A included 22 cases in the first
      five years from January 2004 to December 2008, and group B had 34 cases in the
      last five years from January 2009 to December 2013. Analysis and statistical
      treatments are performed according to the comparison of the general state,
      severity, therapeutic condition and results in both groups. RESULTS: We found
      that the operation rate of group A is lower than that of group B while the
      average hospitalization and follow-up time of group A are longer than that of
      group B. The re-hospitalization rate of group A is 22.73% (5/22) and is higher
      than 11.76% of group B (4/34). The vagina bleeding rate of group A is 27.27%
      (6/22) and is higher than 2.94% of group B (1/34). CONCLUSIONS: With the
      increasingly deep-rooted concept of minimally invasive technique in gynecology,
      minimally invasive therapy becomes increasingly popular for the treatment of
      caesarean scar pregnancy. The advantages include short treatment period and
      follow-up time and safe therapy which to some extent reduces the burden and
      mental pressure of patients.

PMID- 26221879
TI  - An analysis of the intervention effect of perioperative evidence-based nursing on
      orthopedic trauma patients' vagal reflex.
AB  - OBJECTIVE: to discuss the application value of evidence-based nursing (EBN) on
      orthopedic trauma patients' perioperative vagus reflex intervention effect.
      PATIENTS AND METHODS: Eighty-six patients were selected, who were hospitalized in
      orthopedics department of our hospital because of trauma from March, 2013 to
      March, 2014. Then, they were divided into the control group (n = 41 cases) and
      the treatment group (n = 45 cases) according to random number table after
      obtaining the consent of the Hospital Ethics Committee and the informed consent
      of the patients as well as their relatives. Control group patients were treated
      with conventional nursing before, during and after operation, and treatment group
      patients were treated with EBN. Then, the incidence of vagal reflex on the two
      groups of patients was compared. HRV frequency domain was applied to analyze the
      differences of autonomic nervous function changes on the two groups of patients,
      and ELISA test was taken to detect the differences of the concentration change of
      serum TNF-alpha and IL-6. RESULTS: The prevalence of vagal reflex on patients in
      treatment group was significantly lower than that in the control group, with
      statistically significant difference (p < 0.05); low frequency (LF) and high
      frequency (HF) on patients from both groups decreased after treatment while LF/HF
      increased, and LF and HF on patients of the treatment group decreased more
      significantly and LF/HF increased more significantly than those of the control
      group, with statistically significant difference (p < 0.05); the concentration of
      TNF-alpha and IL-6 on both groups of patients after nursing also decreased, and
      the treatment group decreased more significantly, with statistically significant
      difference (p < 0.05). CONCLUSIONS: EBN could reduce the prevalence of vagal
      reflex to some extent on perioperative orthopedic trauma patients. It might be
      because EBN could improve vagal tone and reduce the concentration of TNF-alfa and
      IL-6.

PMID- 26221880
TI  - Epigenetic changes of the Klotho gene in age-related cataracts.
AB  - OBJECTIVE: To determine the mRNA and protein expression, and methylation levels
      of the Klotho in lens epithelial cells (LECs) of normal transparent lenses and
      age-related cataracts (ARCs), and to explore the role of epigenetic changes of
      the Klotho gene in regulating the development of ARCs. PATIENTS AND METHODS: A
      total of 90 subjects were divided into three groups: a young adult group with
      normal transparent lenses aging from18 to30 years, a middle-aged group with ARC
      aging from 40 to 49 years, and an elderly group with ARC aging from 67 to 85
      years. The LECs were collected through curvilinear capsulorhexis. The mRNA
      expression of the Klotho gene was determined using the reverse transcription
      polymerase chain reaction (RT-PCR). Protein expression of the Klotho gene in LECs
      was detected using immunohistochemical (IHC) staining. The methylation specific
      polymerase chain reaction (MSP) was used to detect the methylation level of the
      target gene. RESULTS: Decreased mRNA expression of the Klotho gene was reversely
      correlated with age. IHC results showed that the Klotho was mainly expressed in
      the cell membrane and cytoplasm of LECs. It was strongly positive in the young
      adult group (100.0%), with even distribution; weakly positive in the middle-aged
      group (36.7%), with expression distributed 4-5 mm away from the center of the
      anterior lens capsule; and negative in the elderly group (0.0%). MSP results
      showed that the Klotho gene was highly methylated in the elderly group (93.3%)
      and weakly methylated (56.7%) in the middle-aged group, but barely methylated in
      the young adult group (3.3%). CONCLUSIONS: Klotho were positively expressed in
      the LECs of normal individuals at the mRNA and protein level. Its promoter showed
      increased methylation as age increased, resulting in Klotho gene silencing as
      well as down-regulated expression or no expression of the Klotho protein. These
      epigenetic changes could affect the biological activities of LECs, which provided
      the basis for further studies of the association between the Klotho gene and ARC.

PMID- 26221881
TI  - Postoperative care in finger replantation: our case-load and review of the
      literature.
AB  - OBJECTIVE: Technical success of a finger replantation depends on several factors
      such as surgical procedure, type of injury, number of segments amputated,
      amputation level and individual patient factors. Among early complications that
      can occur in this type of surgery the onset of venous or arterial thrombosis is
      the most dreaded. Local irrigating solutions, oral and intravenous
      anticoagulants, thrombolytic agents, plasma expanders, vasodilating, and
      antiaggregant drugs are routinely used in patients undergoing microvascular
      procedures, but currently there is only a non-standardized practice based on
      anecdotal personal experience. MATERIALS AND METHODS: The aim of our study is to
      review selected literature relating to perioperative therapy in microsurgical
      digital replantation. We also report our case-load of 16 patients with finger
      avulsion describing our particular protocol for postoperative anticoagulation and
      restoration of fluid and electrolyte balance. RESULTS: Following our daily
      pharmacological protocol, the postoperative course of the replanted fingers was
      uneventful. The survival rate for finger replantations performed was 100% (n =
      16) with no need for surgical revisions. CONCLUSIONS: The association Dextran
      40/Heparin/fluids in the proposed standardized pro-weight pharmacological
      protocol is an optimal postoperative prophylactic/therapeutic plan to reduce the
      incidence of endovascular thrombosis after replantation, so ensuring high rate of
      success in microvascular surgery.

PMID- 26221882
TI  - Determination of breath alcohol value after using mouthwashes containing ethanol
      in healthy young adults.
AB  - OBJECTIVE: To evaluate breath alcohol value and blood alcohol concentration after
      using mouthwashes containing ethanol in a panel of healthy young adults. To
      determine zeroing time of these values and if subjects' body mass index or gender
      influenced it. Breathalyzer test is a practice performed to detect alcohol
      impaired-drivers that can be penalized. Sometimes Italian judges revoke the
      penalty justifying that the presence of residual ethanol in the oral cavity can
      cause false positive values. PATIENTS AND METHODS: Our study involved 40 young
      adult volunteers; the cohort was composed of University students aged between 21
      and 30 years. They underwent a medical examination to evaluate BMI. We selected
      four alcoholic mouthwashes available on the market with a different ethanol
      amount and an ethanol/ water (10/90) mixture as a reference. Breath alcohol
      concentration values were collected using a portable breathalyzer immediately
      after the rinse (T0), after 10 and 20 minutes (T10 and T20). We evaluated blood
      alcohol concentration 5 minutes after the rinse. RESULTS: All T10 values are
      lower than 0.5 g/L (Italian BAC driving limit). Differences between average
      values at T0-T10 are statistically significant (p < 0.05). Correlations between
      BAV and BMI are not statistically significant respectively at T0 (A: p = 0.54. B:
      p = 0.96. C: p = 0.93. D: p = 0.53) and T10 (A: p = 0.42. C: p = 0.99. D: p =
      0.66). Differences between male and female groups aren't statistically
      significant (A: p = 0.49; B: p = 0.79; C: p = 0.97; D: p = 0.06). CONCLUSIONS:
      High BAV values determined at T-0 are a consequence of residual ethanol present
      in the oral cavity, the zeroing time of these ones (oppure thereof) is very
      swift. Our study shows that rinsing with an alcoholic mouthwash before undergoing
      the breathalyzer test does not realistically influence the result.

PMID- 26221883
TI  - Outcomes of cardiopulmonary resuscitation in trauma patients in the Emergency
      Department.
AB  - OBJECTIVE: We aimed to determine our performance and factors effecting outcomes
      in cardiopulmonary resuscitation (CPR) for the patients with trauma in the
      Emergency Department (ED). PATIENTS AND METHODS:   In a period of 5 years, file
      data of 136 consequtive adult trauma patients who have required CPR in our ED
      were collected, retrospectively. Patients were divided into subgroups according
      to years, mechanism of trauma, hour of the trauma, location of cardiac arrest,
      the period of the CPR, the rhythm during the onset of arrest, atropine use and ED
      specialist accompaniment. Patients were also divided into two subgroups as those
      who died in the ED and those who survived. RESULTS: The leading cause of trauma
      was motor vehicle accidents. The period between arrest and CPR was 0-5 minutes in
      92 patients. Of these 92 patients 12 have survived and as the time prolonges,
      number of survivors tended to decrease. The most common rhythm determined shortly
      before cardiac arrest was asystole. When all patients with trauma requiring CPR
      were considered, overall rate of survival was found to be 9.5%. When an ED
      specialist accompanied, survival rate increased. According to the rates of
      survival, atropine was found to be useless. CONCLUSIONS: Our results revealed
      that, when performed in the leadership of an ED specialist, more successful
      outcomes may be obtained in CPR in trauma patients. We also determined that use
      of atropine does not contribute to survival rate. As CPR prolonges, the success
      rate falls.

PMID- 26221884
TI  - Coronary artery aneurysms: case report and treatment overview.
AB  - Coronary artery aneurysms (CAAs) are localized dilatations exceeding the diameter
      of adjacent normal coronary segments. These conditions, even rare, still
      represent an important risk factor for the patient life. 

PMID- 26221885
TI  - Prevalence of post-operative morbidity risk factors following cardiac surgery in
      patients with chronic viral hepatitis: a retrospective study.
AB  - OBJECTIVE: Current cardiac risk assessments such as EuroSCORE II and the STS
      Score do not take liver dysfunction into account. The purpose of this study was
      to evaluate the prevalence and post-operative morbidity risk factors following
      cardiac surgery of patients with chronic viral hepatitis. PATIENTS AND METHODS:
      The study group consisted of 105 patients with documented chronic viral hepatitis
      who were subject to elective cardiac surgery from 2001 to 2012. Subjects were
      evaluated for pre-operative liver dysfunction according to the MELD score.
      RESULTS: The average MELD score of the study group was 10.00 +/- 6.00. The
      average EuroSCORE ii of the study group was 2.07% +/- 1.62%. The primary post
      operative complication was cardiac complications (n=57, 54.3%). Analysis showed
      significant differences in meld score, bilirubin and smoking. Multivariate
      logistic regression analysis showed that the variables entering into the model
      included such risk factors with a significant or near significant (p < 0.2)
      influence on hospital morbidity and consisted in valve vs. coronary artery
      disease, valve/cad, aortic valve replacement vs. Coronary artery bypass graft,
      and bilirubin (mg/dl). CONCLUSIONS: it is vital that liver dysfunction is added
      to the risk models which are currently utilized to predict the post-operative
      morbidity of cardiac surgery patients.

PMID- 26221886
TI  - Matrix metalloproteases as a pharmacological target in cardiovascular diseases.
AB  - OBJECTIVE: Matrix metalloproteases (MMPs) are involved in the development and the
      progression of atherosclerosis and are related to an elevated risk of
      cardiovascular morbidity and mortality. An altered profile of MMPs and their
      tissue inhibitors (TIMPs) has been demonstrated in arterial hypertension,
      diabetes mellitus, obesity, metabolic syndrome and in cardiovascular disorders,
      such as coronary artery disease, atrial fibrillation, and heart failure.
      MATERIALS AND METHODS: The aim of this review was to examine the literature data
      regarding the possible effects of some molecules, commonly employed in subjects
      with cardiovascular disease, on the expression and the activity of MMPs and
      TIMPs. A search was conducted with PubMed, Medline, using combinations of the
      terms "matrix metalloproteases," "TIMP," "activity regulation," "pharmacological
      therapy," "cardiovascular disease," "antihypertensives," "antidiabetic drugs,"
      "statins" and "antiplatelet agents". Review articles were also searched. RESULTS:
      Several drugs, and in particular diuretics, calcium-channel blocker, angiotensin
      receptor blockers, ACE inhibitors, statins, antidiabetic and antiplatelet agents,
      seem to influence, in different ways, the MMP pattern with beneficial effects on
      cardiovascular outcomes. CONCLUSIONS: Keeping in mind these findings, the
      therapeutic strategy must be reconsidered in order to obtain a sensible MMP
      inhibition.

PMID- 26221887
TI  - Factors contributing to cognitive deficits in elderly residents of rural areas.
AB  - OBJECTIVE: Due to the growing aging of societies an increasingly large group of
      people suffers from age-related impairment of cognitive functions and thus
      reducing the quality of life of the elderly. The purpose of the study was to
      evaluate the efficiency of cognitive functions in a group of aging residents of
      rural areas. PATIENTS AND METHODS: The inhabitants of a rural area were recruited
      and assessed: cognitive function as well as intellectual and physical activity,
      number of years of education, presence of diseases, using stimulants, diet,
      sources of living, marital status and family situation Subjects were divided into
      two groups: persons above 65 and older, constituting the studied group and
      persons between 40 and 64 years of age, constituting the control group. Both
      groups did not significantly differ in terms of sex or years of education.
      RESULTS: Statistically significant differences (p < 0.05) were found in the
      results of the tests concerning such functions as the sight recognition memory
      and spatial recognition memory, spatial operating memory both on the strategy
      level and on the level of committed errors. An analysis of the results obtained
      in the group of elderly people did not indicate any major differences between men
      and women as regards the analyzed cognitive functions, no statistically
      significant differences were found in cognitive testing depending on the number
      of years of education. The studied persons included in the physically active
      group scored better in the visual memory and learning tests. CONCLUSIONS: The
      conducted studies elucidated the dependence of the level of cognitive functions
      on age, a positive impact of physical activity on some cognitive functions,
      however we could not find differences between the efficiency of those functions
      and education, sex, presence of somatic diseases and activity of persons aged >
      65.

PMID- 26221888
TI  - Microsurgery for ruptured cerebellar arteriovenous malformations.
AB  - OBJECTIVE: To summarize the clinical features of ruptured cerebellar
      arteriovenous malformations (AVMs) and to explore surgical methods and outcomes
      in ruptured cerebellar AVM patients. PATIENTS AND METHODS: In the past 14 years,
      67 patients with cerebellar AVMs were treated at our institution, accounting for
      14.9% of the total vascular malformation patients in our department. In this
      study, we retrospectively analyzed the clinical characteristics, operation
      indication, surgery techniques, and prognoses of these cases. RESULTS: Among the
      67 AVM cases, the distribution of Spetzler-Martin grades was 32 Grade I, 14 Grade
      II, 13 Grade III, 5 Grade IV, and 3 Grade V cases. Microsurgical treatment was
      carried out via the retrosigmoid approach or suboccipital midline approach. After
      the surgery, the distribution of GOS grades was 60 Grade V, 3 Grade IV, 1 Grade
      III, 2 Grade II, and 2 Grade I cases. CONCLUSIONS: Microsurgical removal should
      be performed in ruptured cerebellar AVM patients as early as possible once the
      preoperative and postoperative preparations were done. Good surgical effects were
      obtained by using proper surgery techniques and the right protection of critical
      cerebral structures. Patients with a GCS grade of >= 8 showed good recovery, but
      patients with a grade of < 8 had poor prognoses.

PMID- 26221890
TI  - Recurrent ischemic events and risk factors in patients with symptomatic
      intracranial artery stenosis.
AB  - OBJECTIVE: To evaluate the recurrent ischemic events and risk factors in patients
      with symptomatic intracranial artery stenosis. PATIENTS AND METHODS: Patients
      with acute cerebral infarction or transient ischemia attach (TIA) and
      intracranial arterial stenosis confirmed through CTA examination, were enrolled
      from the Department of Neurology. All cases were followed-up regularly and
      divided into recurrent group and non-recurrent group according to occurrence of
      cerebrovascular events. Major observation index: (1) the occurrence of endpoint;
      (2) new stroke in responsible artery; (3) drug therapy compliance was used.
      RESULTS: A total of 142 cases fulfilled the inclusion criteria, among them 121
      cases (85.2%) completed the follow-up, and in 16 cases (13.2%) ischemic
      cerebrovascular stroke events occurred within one year, while among these
      vascular lesions recurred on the ipsilateral side in 12 cases (75%). Single
      factor analysis showed that difference between recurrent group and non-recurrent
      group on irregular use of statins (p = 0.017), diabetes mellitus (p = 0.017) and
      severe arterial stenosis (p = 0.030) were statistically significant. Logistic
      regression analysis showed that irregular use of statins (OR=3.719, p = 0.005),
      diabetes (OR=1.842. p = 029) and severe arterial stenosis (OR=1.503. p = 0.045)
      were correlated with the recurrence of symptomatic intracranial artery stenosis.
      CONCLUSIONS: Patients with symptomatic intracranial artery stenosis had a higher
      recurrence rate of stroke; whereas patients with irregular use of statins,
      diabetes and severe arterial stenosis had a higher recurrence risk of stroke.

PMID- 26221889
TI  - Effect of mecobalamin treatment on the recovery of patients with posterior
      communicating artery aneurysm inducing oculomotor nerve palsy after operation.
AB  - OBJECTIVE: This research aims to evaluate the effect of mecobalamin treatment on
      the recovery of patients with posterior communicating artery aneurysm inducing
      oculomotor nerve palsy after embolization. PATIENTS AND METHODS: A total of 56
      patients with oculomotor nerve palsy (ONP) attributed to posterior communicating
      artery (PcomA), were admitted and treated in the Neurology Department of Hubei
      College of Medicine affiliated to Xiangyan Hospital from July 2007 to January
      2013, and 55 of them were followed up as well. Among them 27 patients were given
      embolization treatment and 28 received embolization + mecobalamin treatment. The
      recovery condition of ONP were followed and compared one year after the
      treatment. RESULTS: All patients were followed up for more than a year. And 31
      patients (56.4%) out of 55 achieved complete recovery, 19 (34.5%) attained
      partial recovery and 5 (9.1%) had no recovery from ONP. Whereas, 20 patients
      (71.4%) in the embolization + mecobalamin treatment group achieved complete
      recovery and 11 (40.7%) in the embolization treatment group achieved partial
      recovery, and the comparative difference was statistically significant (p <
      0.05). CONCLUSIONS: Endovascular is highly efficacious treatment for ONP-inducing
      PcomA and can promote the recovery of oculomotor nerve palsy after embolism.

PMID- 26221891
TI  - The clinical efficacy of neuronavigation-assisted minimally invasive operation on
      hypertensive basal ganglia hemorrhage.
AB  - OBJECTIVE: To explore the therapeutic effect of neuronavigation-assisted
      minimally invasive operation on hypertensive basal ganglia hemorrhage patients
      with hematoma volume less than 30 mL. PATIENTS AND METHODS: 25 hypertensive basal
      ganglia hemorrhage patients with hematoma volume varied from 15 to 30 mL were
      enrolled. 13 patients were recuited to undertook puncture aspiration and catheter
      drainage under real-time neuronavigation. The operations were carried out under
      CT imaging guidance. Twelve patients with conservative treatment were recruited
      as control. RESULTS: Neuronavigation operation group was superior to the
      conservative treatment group in terms of hematoma clearance time, duration of
      hospitalization, 6-month Glasgow coma score (GCS) scores and neurological
      deficiency scores. CONCLUSIONS: Neuronavigation-assisted minimally invasive
      operation is suitable for low volume hypertensive basal ganglia hemorrhage and
      improves the prognosis of these patients significantly.

PMID- 26221892
TI  - Vascular endothelial growth factor increases GEnC permeability by affecting the
      distributions of occludin, ZO-1 and tight juction assembly.
AB  - OBJECTIVE: To explore the molecular mechanism of the increased permeability of
      glomerular endothelial cells (GEnC) stimulated by vascular endothelial growth
      factor (VEGF). METHODS: We investigated the permeability-increasing effect and
      tight junction formation of VEGF by measuring FITC labeled BSA across GEnC
      monolayer. Then, immunofluorescence and western blot were employed to detect the
      distributions of occludin and ZO-1. RESULTS: We found that VEGF increased FITC
      BSA permeability. VEGF also caused a loss of occludin and ZO-1 from the
      endothelial cell junctions, and changed the staining pattern of the cell
      boundary. Western blot analysis of GEnC lysates revealed that occludin and ZO-1
      were redistributed under VEGF treatment. CONCLUSIONS: These results suggested
      that VEGF could increase GEnC monolayer permeability by changing distributions
      and organizations of occludin and ZO-1, which lead to tight junction disassembly.
      Occludin and ZO-1 appeared to be downstream effectors of the VEGF signaling
      pathway.

PMID- 26221894
TI  - Hypereosinophilic obliterative bronchiolitis with an elevated level of serum CEA:
      a case report and a review of the literature.
AB  - A 44-year-old man presented with chronic, persistent cough and occasional
      wheezing. Airflow obstruction, blood eosinophilia and a remarkable elevated level
      of serum carcinoembryonic antigen (CEA) were found. Radiographic and pathological
      studies confirmed eosinophilic bronchiolitis. There was no evidence of neoplasms
      by extensive examinations. After a protracted oral steroid therapy, the blood
      eosinophil count, the serum CEA level and the lung lesions were all improved in
      parallel, whereas fixed airflow obstruction remained. This case was diagnosed as
      a new distinct syndrome, hypereosinophilic obliterative bronchiolits. Serum CEA
      and blood eosinophil cell count served as good markers of the disease condition
      for this syndrome. 

PMID- 26221893
TI  - A case of abdominal pain with dyslipidemia: difficulties diagnosing cholesterol
      ester storage disease.
AB  - Cholesterol ester storage disease is an exceptionally rare dyslipidemia with less
      than 150 cases reported in the medical literature. The diagnosis of Cholesterol
      Ester Storage Disease is often missed by virtue of the fact that the symptoms
      mimic both inborn metabolic defects and hepatic steatosis. Patients with
      Cholesterol Ester Storage Disease usually present with atypical complaints
      including abdominal pain from altered gut motility. Blood analysis typically
      reveals abnormal liver function tests with coincident dyslipidemia. We present a
      case of a young woman with Cholesterol Ester Storage Disease who was followed
      over two decades. We discuss issues common to her initial protracted diagnosis
      with management options over time. 

PMID- 26221895
TI  - Efficacy of subcutaneous immunoglobulins in primary immunodeficiency with Crohn's
      like phenotype: report of a case.
AB  - Common variable immune deficiency (CVID) is the most frequent primary
      immunodeficiency in adults. In CVID, the prevalence of gastrointestinal
      manifestations ranges between 2 and 50% with a complication-related morbidity
      second only to that of the respiratory tract. In some cases, clinical and
      endoscopic features are undistinguishable from those of inflammatory bowel
      disease (IBD). We describe the case of a 28-year-old man in which a diagnosis of
      Crohn's disease was firstly suspected. Subsequently, a diagnosis of Crohn's-like
      disease in a patient with CVID was made and a replacement therapy with human
      normal immunoglobulin intravenously was started. Unfortunately, serum IgG levels
      remained below 2.0 g/l in pre-infusional controls with persistence of
      gastrointestinal symptoms and malnutrition despite anti-inflammatory therapy
      (mesalazine, corticosteroids). Then, the patient began treatment with human
      normal immunoglobulins administered subcutaneously. The follow-up visits showed a
      progressive increase in serum IgG. Moreover, the patient reported improvement of
      gastrointestinal symptoms with reduction of diarrhoea, and laboratory tests
      showed a progressive and significant improvement. We confirm that therapy with
      subcutaneously administered immunoglobulins is safe and effective. In addition,
      our observations indicate that, for patients with CVID and enteropathic
      complications, replacement therapy with subcutaneous IgG may be the treatment of
      choice. 

PMID- 26221896
TI  - Effect of vascular bradykinin on pancreatic microcirculation and hemorheology in
      rats with severe acute pancreatitis.
AB  - OBJECTIVE: To investigate the effect of vascular bradykinin on pancreatic
      microcirculation and hemorheology in rats with severe acute pancreatitis (SAP).
      MATERIALS AND METHODS: Ninety male Wistar rats were randomly divided into a blank
      control group, an SAP group and a vascular bradykinin treatment group. The SAP
      model was induced by the retrograde injection of 5% sodium taurocholate in the
      pancreaticobiliary duct. The vascular bradykinin treatment group underwent
      gastrostomy, with a fine plastic tube placed in the stomach that led out of body
      through the abdominal wall.Vascular bradykinin was fully dissolved and
      administered at a dose of 20 U/kg once every 8 h. The pancreatic microcirculatory
      blood flow volume and velocity, microvascular permeability, hemorheology were
      evaluated respectively by double-channel laser Doppler flowmetry, the Evans blue
      leakage test, a blood rheology test instrument. RESULTS: The pancreatic
      microcirculatory blood flow volume and velocity in the vascular bradykinin
      treatment group increased gradually after 48 h compared with the SAP group, and
      the changes were significantly different (p < 0.05). The pancreatic microvascular
      permeability of the vascular bradykinin treatment group was significantly reduced
      after 48 h compared with the SAP group (p < 0.05). The low shear rate blood
      viscosity, hematocrit and erythrocyte aggregation index of the vascular
      bradykinin treatment group were significantly decreased after 48 h compared with
      the SAP group (p < 0.05). CONCLUSIONS: Vascular bradykinin can improve pancreatic
      microcirculation and hemorheology in rats with severe acute pancreatitis.

PMID- 26221897
TI  - The determinations of nucleosome positioning.
AB  - OBJECTIVE: Nucleosomes are the basic packaging units of chromatin, determinants
      of nucleosome organization playing a major role in genome packaging. Although a
      wide variety of nucleosome organization factors have been considered separately
      across the whole or partial human genomic regions, it is unclarified that what
      the major determinants and their roles in scale are when being put all together.
      And it is also unknown that what the similarities and differences of determinants
      between different genomic features such as genes of different expression levels
      or genomic regions with different functions. MATERIALS AND METHODS: We detected
      commonalities and characteristics of nucleosome positioning determinants in
      different genes and regions with 1591486 nucleosomes identified by ourselves in
      human CD4+ cell. RESULTS: It was found that a distinct linear combination of
      about 20 nucleosome-positioning factors explained nucleosome occupancy for each
      genomic feature. In those linear combinations, 6 DNA sequence attributes (Roll
      stiffness and Twist stiffness, CT and AG, CG and shift stiffness) and a histone
      modification (H4R3me2) are shared. And other factors are varied. Roll stiffness
      and Twist stiffness are the most important features. They are dominant, alone
      explaining 96.61-98.45% of the positioning weight in each genomic feature. The
      characteristic factors in each combination are larger in number, but weaker in
      power. Numerous histone modifications play a subtle role for nucleosome
      positioning. CONCLUSIONS: The present study provides a more accurate positioning
      nucleosome-map with higher resolution and a dramatically simplified means to
      predict and understand intrinsic nucleosome occupancy in different genomic
      features in human CD4+ cell. Roll stiffness and Twist stiffness are the two most
      important determinants in all genomic features. They may dominate because they
      both determine the degree of DNA bending and correlates with many other DNA
      structural characteristics. Histone modifications play a role of subtle
      allocation for nucleosome occupancy.

PMID- 26221898
TI  - Clinical perspectives on mesenchymal stem cells promoting wound healing in
      diabetes mellitus patients by inducing autophagy.
AB  - BACKGROUND: The pathogenesis of wound healing in diabetes mellitus is
      complicated, and results in less effective healing. Mesenchymal stem cells (MSCs)
      have been thought to promote wound healing in diabetes. However, the underlying
      mechanisms are not well understood. Autophagy plays an important role in wound
      healing. It has been speculated that the mesenchymal stem cells derived from the
      umbilical cord can improve wound healing in diabetes mellitus by inducing
      autophagy. Hence, we reviewed the research progress in this field to identify new
      strategies of clinical treatment for wound healing in diabetes mellitus.

PMID- 26221899
TI  - Dynamic compression combined with exogenous SOX-9 promotes chondrogenesis of
      adipose-derived mesenchymal stem cells in PLGA scaffold.
AB  - OBJECTIVE: Mechanical stimuli play a crucial role in cartilage repair and
      regeneration. Dynamic compression, as a physical stimulus, has been demonstrated
      to be an important factor in regulating the proliferation and differentiation of
      adipose-derived mesenchymal stem cells (ADSCs). However, the interaction of
      mechanical stimuli and chondrogenesis regulator on the chondrocyte phenotype and
      differentiation of ADSCs remains unknown. In the present study, we investigated
      the effects of dynamic compression combined with exogenous SOX-9 on
      chondrogenesis of ADSCs in a three-dimensional porous polylactic-co-glycolic acid
      (PLGA) scaffold. MATERIALS AND METHODS: The morphology of ADSCs on the scaffolds
      was examined using scanning electron microscopy (SEM). The proliferation of ADSCs
      was evaluated by MTT assay. The expression of cartilage-specific genes in early
      chondrogenic differentiation was assessed by real-time PCR. RESULTS: Our results
      indicated that the combination of dynamic compression with exogenous SOX-9
      induces the expression of chondrogenic genes and promotes the proliferation of
      ADSCs. CONCLUSIONS: Therefore, compression and SOX-9 have positive effects on
      chondrogenesis process of ADSCs, which may benefit articular cartilage
      regeneration.

PMID- 26221900
TI  - Comparison of minimal residual disease (MRD) monitoring by WT1 quantification
      between childhood acute myeloid leukemia and acute lymphoblastic leukemia.
AB  - OBJECTIVE: Wilms tumor gene 1 (WT1) has been identified as an independent risk
      prognostic factor in acute leukemia. However, there exists a controversy that WT1
      as a marker for minimal residual disease (MRD) monitoring in acute leukemias. We
      detected WT1-RNA transcript level to estimate the diagnostic value of monitoring
      MRD in childhood acute myeloid leukemia (AML) and acute lymphoblastic leukemia
      (ALL). PATIENTS AND METHODS: WT1 mRNA expression levels were detected by real
      time quantitative reverse transcriptase PCR (qRT-PCR) in bone marrow (BM) samples
      from 107 childhood ALL and 35 childhood AML at diagnosis. MRD was consecutively
      performed after induction and consolidation (early intensification in ALL)
      chemotherapy. Receiver operating characteristics (ROC) analysis and the largest
      areas under the curve (AUC) were applied to define optimal threshold value of MRD
      level. Sensitivity, specificity, positive likelihood ratio (+LR) and negative
      likelihood ratio (-LR) were used to evaluate diagnostic power for MRD. Relapse
      free survival (RFS) was evaluated by the Kaplan-Meier statistical method.
      RESULTS: The largest areas under the curve (AUC), specificity, +LR and -LR showed
      higher accuracy in childhood AML than ALL. Compared the diagnostic parameters,
      the post-induction time wasn't good enough to show the better time than post
      consolidation time for MRD assessment in AML. The threshold was set at 150 WT1
      copies/104 ABL copies as the optimal cut-off value of MRD level post induction in
      childhood AML. MRD+ (WT1>150) children had increased the risk of relapse with
      poor prognosis, showing lower RFS than MRD- group (p=0.01). However, the
      threshold 70 WT1 copies/104 ABL copies post induction in childhood ALL did not
      show clinical significance for predicting prognosis (p=0.056). CONCLUSIONS: WT1
      gene will be a useful marker for monitoring MRD to predict relapse in childhood
      AML. But it did not show good enough to monitor MRD in childhood ALL.

PMID- 26221901
TI  - Transfusion of stored red blood cells in critically ill trauma patients: a
      retrospective study.
AB  - OBJECTIVE: The many published studies on the effects of the transfusion of stored
      red blood cells on clinical outcomes yielded discordant results. Therefore, we
      chose to study patients with severe trauma. The clinical outcomes considered
      included in-hospital mortality, the occurrence of sepsis, length of stay in
      intensive care unit and in hospital, and days of mechanical ventilation. PATIENTS
      AND METHODS: We selected all patients with traumatic injury, who received at
      least 2 red cell units in the first day of admission. Patients were divided into
      two groups: those who had received fresh red cells only (fresh group) and those
      who had received at least one "old" red cell unit (old group). The red cells were
      considered fresh if they had been stored <14 days. RESULTS: The fresh and old
      groups included 376 and 321 patients, respectively. Baseline demographic and
      clinical characteristics were comparable between the groups. However, old group
      received more red cell and plasma units during whole hospital stay (red cells: 11
      +/- 7 vs 6 +/- 4, p < 0.001; plasma: 7 [0-9] vs 3 [0-6]). Among outcomes, only
      length of stay in intensive care unit (old vs fresh: 18 +/- 9 vs 12 +/- 8 days, p
      < 0.001) and in hospital (77 +/- 35 vs 45 +/- 30 days, p < 0.001) differed
      significantly between groups. The association remained statistically significant
      in a multivariate analysis including known confounding factors. CONCLUSIONS:
      Patients with major trauma transfused with old (>=14 days) red cells had a longer
      length of stay in intensive care unit and in hospital, without any difference in
      mortality, occurence of sepsis or days of mechanical ventilation.

PMID- 26221902
TI  - miR-206 inhibits human laryngeal squamous cell carcinoma cell growth by
      regulation of cyclinD2.
AB  - OBJECTIVE: Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly
      expressd in many malignancies and crucial to tumorigenesis. Herein, we identified
      the role and mechanism of miR-206 in laryngeal squamous cell carcinoma (LSCC)
      growth. PATIENTS AND METHODS: Quantitative real-time PCR was performed to detect
      the relative expression level of miR-206 in LSCC tissues. Crystal violet and flow
      cytometry were conducted to explore the effects of miR-206 on the proliferation
      and cell cycle of human LSCC cell line, respectively. The impact of miR-206
      overexpression on putative target cyclinD2 were subsequently verified via Western
      blot. Tumor growth assay was performed to testify the effect of miR-206 on the
      tumor growth in vivo. RESULTS: MiR-206 expression was frequently (p < 0.05) down
      regulated in LSCC specimens. Overexpression of miR-206 in Hep-2 cell inhibited
      the proliferation by blocking the G1/S transition as well as suppressed the
      growth of xenograft tumors in mice, implying that miR-206 functions as a tumour
      suppressor in the progression of LSCC. Overexpression of miR-206 significantly
      decreased (p < 0.05) the protein level of cyclinD2, which has previously been
      identified as a direct targets of miR-206. CONCLUSIONS: Altogether, our results
      identify a crucial tumour suppressive role of miR-206 in LSCC growth, at least
      partly via up-regulation of cyclinD2 protein levels, and suggest that miR-206
      might be a candidate prognostic predictor or an anticancer therapeutic target for
      LSCC patients.

PMID- 26221903
TI  - Integrated analysis of gene expression profile and genetic variations associated
      with ovarian cancer.
AB  - OBJECTIVE: Ovarian cancer is the most lethal gynecologic cancer worldwide, since
      most patients are diagnosed at an advanced stage. To improve the early diagnosis
      and treatment of ovarian cancer, we performed a integrated analysis of
      transcription profile and genetic variations to study on the molecular
      pathogenesis in ovarian cancer. METHODS: mRNA expression profiles of ovarian
      cancer and normal controls downloaded from ArrayExpress database were applied to
      identify differentially expressed genes (DEGs). The chromosomal distributions of
      these DEGs were established using DAVID. Then, DNASeq data from the Cancer Genome
      Atlas (TCGA) were extracted to analyze gene mutational information including the
      number of mutations (mut), the number of mutational genes (mutG) and chromosomal
      distributions of mutations. Statistical method was offered to carrying on
      correlation analysis of gene mutations and differential expression. RESULTS: A
      total of 1732 DEGs were identified, and the chromosomal distributions of 97 genes
      were unknown. These DEGs were most significantly distributed on chromosome 4 with
      p value = 1.34E-7. Chromosome 1 enriched the most DEGs (11.56%). Statistical
      algorithm showed that DEGs presented significantly positive correlation with mut
      (p = 0.000009) and mutG (p = 0.00001). In 48.7% DEGs, gene mutations were found.
      CONCLUSIONS: We conducted scientific analysis on integration of DEGs in
      expression profiles and genetic mutations in ovarian cancer, displayed the
      correlation of differential expression and genetic variations. The result
      indicated that expression profiles were significantly correlated to genotype.

PMID- 26221904
TI  - Comparison of snakebite cases in children and adults.
AB  - OBJECTIVE: There are very few studies that compare the snakebite cases in
      children and adults. The present study aimed to compare the demographic
      characteristics, clinical presentations, laboratory findings, and developed
      complications in pediatric and adult patients due to snakebites. PATIENTS AND
      METHODS: This study included the patients admitted to the hospital and monitored
      due to snakebite between July 1999 and December 2012. The condition of each
      patient who had been bitten was admitted to the hospital was monitored from the
      time of admission to the end of their hospital stay. The fact that a snakebite
      occurred was recorded if the subjects saw the snake or if the appearance of the
      puncture sites was convincingly a snakebite. RESULTS: The present work included
      290 patients, of whom 123 were children and 167 were adults. The most common
      location of the bites was the lower extremity with 78.9% (n=97) and 63.5% (n=106)
      in pediatric and adult patients, respectively. All of the pediatric patients
      received prophylactic treatment with antibiotics, whereas 62 (37.1%) adult
      patients received antimicrobial treatments due to the soft tissue infection. The
      most common complication developed was pulmonary edema in children at a rate of
      33.3% (n=41) and compartment syndrome in adult patients at a rate of 3% (n=5).
      CONCLUSIONS: Patients admitted to the hospital due to snakebite should be
      monitored for at least 12 hours, even if there is no sign of clinical
      envenomation. Antivenom treatment should be administered to the patients
      requiring clinical staging. Patients should be kept under close monitoring to
      prevent the development of serious complications such as cellulitis, pulmonary
      edema, compartment syndrome, and disseminated intravascular coagulation.

PMID- 26221905
TI  - Protective effects of alpha-lipoic acid against benzene induced toxicity in
      experimental rats.
AB  - OBJECTIVE: The aim of the present study was to examine the potential protective
      effects of Alpha-Lipoic Acid (ALA) against benzene induced alteration in CYP2E1
      gene function, DNA damage as well as the oxidant-antioxidant status. MATERIALS
      AND METHODS: Fifty adult male Wister rats were used for this study. Rats were
      randomized and divided into four groups: Group I was designated as control group
      and received a vehicle of olive oil; Group II was received alpha lipoic acid in a
      dose of (20 mg/kg, i.p.); Group III received only I.M. injection of benzene in a
      dose of 2 ml/kg. Group IV received both alpha lipoic acid in a dose of (20 mg/kg,
      i.p.) and I.M. injection of benzene in a dose of 2 ml/kg. The animals were
      treated on each alternate day for 30 days then all rats were sacrificed and both
      blood and liver tissue samples were taken to measure serum malondialdehyde (MDA)
      Level; serum level of reduced glutathione (GSH); level of serum 8-hydroxy-2'
      deoxyguanosine; hepatic microsomal cytochrome P450 2E1 activity and gene
      expression. RESULTS: Benzene significantly increased serum malondialdehyde (MDA),
      8-hydroxy-2'-deoxyguanosine (8-OHdG) and both CYP2E1 activity and gene expression
      but significantly decreased level of reduced glutathione (GSH). These changes are
      reversed upon administration of ALA. CONCLUSIONS: The current study provided
      evidence that the linkage between CYP2E1-dependent oxidative stress, DNA damage,
      and GSH homeostasis could contribute to the toxic actions of benzene which can be
      counteracted by ALA by its suppression action on CYP2E1, inhibition of lipid
      peroxidation and oxidative DNA damage as well as maintenance of intracellular
      antioxidants status.

PMID- 26221906
TI  - Electron microscopic examination of the effects of methyl parathion exposure on
      the ovaries.
AB  - OBJECTIVE: In our study, we aimed to investigate histopathological effects of
      chronic methyl parathion exposure on ovaries at electron microscopic level.
      MATERIALS AND METHODS: In this study, Wistar albino type, adult, female rats with
      an average weight of 190-250 g were used. 30 female rats, included in this study,
      were divided into 3 groups. Group I received only saline and was evaluated as the
      control group, whereas Group II received 1/50 percent of LD50 dose of methyl
      parathion and Group III received 1/20 percent of LD50 dose of methyl parathion
      every day at 130 pm orally by gavages during two estrus cycles (8 days). The rats
      at proestrus stage on the morning of 9th day of the study underwent bilateral
      ovariectomy. Ovarian tissues of the control and drug groups were examined under
      the electron microscope; primordial and growing follicles were included in the
      evaluation, however, corpora lutea were excluded taking into account the presence
      of remaining regressive corpora lutea from the previous cycles. RESULTS:
      Following examination of ovarian tissues of rats exposed to 1/50 and 1/20 percent
      of LD50 dose of Methyl parathion at electron microscopic level, it was detected
      that significant structural changes had occurred in developing follicles and
      ovarian stroma in both drug groups, and that primordial follicles had not been
      affected significantly from methyl parathion but necrosis had been developed in
      oocyte and granulosa cells of developing follicles, and that in 1/20 group in
      addition to these changes, apoptotic changes had been found in granulosa cells of
      developing follicles. CONCLUSIONS: As a result of chronic exposure to methyl
      parathion, rat ovaries are significantly affected and follicular development is
      impaired. This state may explain the cause of infertility due to chronic
      pesticide exposure.

PMID- 26221907
TI  - Spontaneous reporting of Stevens-Johnson syndrome and toxic epidermal necrolysis
      associated with antiepileptic drugs.
AB  - OBJECTIVE: To assess the association between Stevens-Johnson syndrome (SJS)/
      toxic epidermal necrolysis (TEN) and antiepileptics including the most recently
      authorized drugs. METHODS: In the Spanish Pharmacovigilance database, we searched
      for spontaneous reports of SJS or TEN associated with antiepileptic drugs and
      analysed: a) reporting odds ratio (ROR), b) age and gender of the patient, c)
      evolution, d) latency and recovery periods and e) presence or absence of other
      suspected drugs. RESULTS: A total of 84 reports of SJS and 80 of TEN related to 9
      antiepileptic drugs were studied. Reports were mainly associated with phenytoin
      (SJS: 28; TEN: 43), lamotrigine (SJS: 37; TEN: 20) and carbamazepine (SJS: 14;
      TEN: 16). Other antiepileptic drugs involved were: valproate, phenobarbital,
      oxcarbazepine, levetiracetam, primidone and gabapentin. Patients were of a median
      age of 40 [1-87] and 57.3% of them were women. Cases related to phenytoin were
      more common in older men and to lamotrigine in younger women. The latency period
      of SJS and TEN did not exceed the first month of treatment and, in most of the
      analysed reports, the outcome was recovery. CONCLUSIONS: Our observations support
      the association of SJS or TEN with phenytoin, carbamazepine, valproate or
      phenobarbital and enlighten the role of lamotrigine and others such as
      oxcarbazepine or levetiracetam.

PMID- 26221908
TI  - Virial pressure in systems of spherical active Brownian particles.
AB  - The pressure of suspensions of self-propelled objects is studied theoretically
      and by simulation of spherical active Brownian particles (ABPs). We show that for
      certain geometries, the mechanical pressure as force/area of confined systems can
      be equally expressed by bulk properties, which implies the existence of a
      nonequilibrium equation of state. Exploiting the virial theorem, we derive
      expressions for the pressure of ABPs confined by solid walls or exposed to
      periodic boundary conditions. In both cases, the pressure comprises three
      contributions: the ideal-gas pressure due to white-noise random forces, an
      activity-induced pressure ("swim pressure"), which can be expressed in terms of a
      product of the bare and a mean effective particle velocity, and the contribution
      by interparticle forces. We find that the pressure of spherical ABPs in confined
      systems explicitly depends on the presence of the confining walls and the
      particle-wall interactions, which has no correspondence in systems with periodic
      boundary conditions. Our simulations of three-dimensional ABPs in systems with
      periodic boundary conditions reveal a pressure-concentration dependence that
      becomes increasingly nonmonotonic with increasing activity. Above a critical
      activity and ABP concentration, a phase transition occurs, which is reflected in
      a rapid and steep change of the pressure. We present and discuss the pressure for
      various activities and analyse the contributions of the individual pressure
      components. 

PMID- 26221909
TI  - Controlled synthesis of a highly dispersed BiPO4 photocatalyst with surface
      oxygen vacancies.
AB  - Highly dispersed BiPO4 with surface oxygen vacancies was synthesized via a
      solvothermal-calcination method. It can disperse uniformly in water for more than
      three days and the optimum photocatalytic activity of this highly dispersed BiPO4
      was more than twice as high as that of Degussa P25 due to the oxygen vacancies.
      The high dispersibility is attributed to a layer of organic matter formed on the
      surface of BiPO4via the solvothermal approach. Most of the organic matter can be
      removed by calcination at 450  degrees C, but a small amount remains, thus the
      calcined BiPO4 retained its high dispersibility. This high dispersibility
      maintains a good contact between BiPO4 and the pollutants, resulting in the
      efficient removal of the pollutants by BiPO4. Besides, calcination at 450 
      degrees C also induced the formation of oxygen defects in BiPO4, which promotes
      the separation of photogenerated charge carriers and thus improves the
      photocatalytic activity of BiPO4. 

PMID- 26221910
TI  - Asymmetric Addition of Pyridyl Aluminum Reagents to Aldehydes Catalyzed by a
      Titanium(IV) Catalytic System of (R)-H8-BINOLate.
AB  - The asymmetric addition of pyridyl aluminum reagents to aldehydes has been
      successfully developed by employing a titanium(IV) catalytic system of (R)-H8
      BINOLate, which affords a series of valuable optically active diarylmethanols
      containing various pyridyl groups in high yields with excellent
      enantioselectivities of up to 98% ee. 

PMID- 26221911
TI  - Improving the Reactivity of Zerovalent Iron by Taking Advantage of Its Magnetic
      Memory: Implications for Arsenite Removal.
AB  - Premagnetization was employed to enhance the reactivity of zerovalent iron (ZVI)
      toward As(III) sequestration for the first time. Compared to the pristine ZVI
      (Pri-ZVI), the rate of As(III) elimination by the premagnetized ZVI (Mag-ZVI) was
      greater over the pHini range of 4.0-9.0 and increased progressively with
      increasing intensity of the magnetic field for premagnetization. Mag-ZVI could
      keep its reactivity for a long time and showed better performance than Pri-ZVI
      for As(III) removal from synthetic groundwater in column tests. The Fe K-edge
      XAFS analysis for As(III)-treated ZVI samples unraveled that premagnetization
      promoted the transformation of ZVI to iron (hydr)oxides and shifted the corrosion
      products from maghemite and magnetite to lepidocrocite, which favored the arsenic
      sequestration. The arsenic species analysis revealed that premagnetization
      facilitated the oxidation of As(III) to As(V). ZVI pretreated with grinding was
      very different from Mag-ZVI with regard to As(III) removal, indicating that the
      improved reactivity of Mag-ZVI should not be associated with the physical
      squeezing effect of the ZVI grains during magnetization. The positive correlation
      between the remanence of Mag-ZVI and the rate constants of total arsenic removal
      indicated that the enhanced reactivity of Mag-ZVI was mainly ascribed to its
      magnetic memory, i.e., the remanence kept by Mag-ZVI. 

PMID- 26221912
TI  - Analysis of a common cold virus and its subviral particles by gas-phase
      electrophoretic mobility molecular analysis and native mass spectrometry.
AB  - Gas-phase electrophoretic mobility molecular analysis (GEMMA) separates nanometer
      sized, single-charged particles according to their electrophoretic mobility (EM)
      diameter after transition to the gas-phase via a nano electrospray process.
      Electrospraying as a soft desorption/ionization technique preserves noncovalent
      biospecific interactions. GEMMA is therefore well suited for the analysis of
      intact viruses and subviral particles targeting questions related to particle
      size, bioaffinity, and purity of preparations. By correlating the EM diameter to
      the molecular mass (Mr) of standards, the Mr of analytes can be determined. Here,
      we demonstrate (i) the use of GEMMA in purity assessment of a preparation of a
      common cold virus (human rhinovirus serotype 2, HRV-A2) and (ii) the analysis of
      subviral HRV-A2 particles derived from such a preparation. (iii) Likewise, native
      mass spectrometry was employed to obtain spectra of intact HRV-A2 virions and
      empty viral capsids (B-particles). Charge state resolution for the latter allowed
      its Mr determination. (iv) Cumulatively, the data measured and published earlier
      were used to establish a correlation between the Mr and EM diameter for a range
      of globular proteins and the intact virions. Although a good correlation resulted
      from this analysis, we noticed a discrepancy especially for the empty and
      subviral particles. This demonstrates the influence of genome encapsulation
      (preventing analytes from shrinking upon transition into the gas-phase) on the
      measured analyte EM diameter. To conclude, GEMMA is useful for the determination
      of the Mr of intact viruses but needs to be employed with caution when subviral
      particles or even empty viral capsids are targeted. The latter could be analyzed
      by native MS. 

PMID- 26221913
TI  - Optimization of the Magnetic Recovery of Hits from One-Bead-One-Compound Library
      Screens.
AB  - On-bead screening of one-bead-one-compound (OBOC) libraries is a useful procedure
      for the identification of protein ligands. An important aspect of this experiment
      is the method by which beads that bind the target protein are separated from
      those that do not. Ideally, such a method would be rapid and convenient and
      result in the isolation of 100% of the "hits" with no false positives (beads that
      display compounds that are not good ligands for the target). We introduced a
      technique in which beads that have bound a labeled target protein can be
      magnetized, thus allowing their convenient isolation ( Astle et al. Chem. Biol.
      2010 , 17 , 38 - 45 ). However, recent work in our laboratory and others has
      shown that magnetic hit recovery can result in the isolation of large numbers of
      false positives and has also suggested that many true hit beads are missed. In
      this study, we employ a well-defined model system to examine the efficiency of
      various magnetic hit isolation protocols. We show that the choice of reagents and
      the particular operations employed are critical for optimal results. 

PMID- 26221914
TI  - Controlling the properties of graphene produced by electrochemical exfoliation.
AB  - The synthesis of graphene with controllable electronic and mechanical
      characteristics is of significant importance for its application in various
      fields ranging from drug delivery to energy storage. Electrochemical exfoliation
      of graphite has yielded graphene with widely varying behavior and could be a
      suitable approach. Currently, however the limited understanding of the
      exfoliation process obstructs targeted modification of graphene properties. We
      here investigate the process of electrochemical exfoliation and the impact of its
      parameters on the produced graphene. Using in situ optical and electrical
      measurements we determine that solvent intercalation is the required first step
      and the degree of intercalation controls the thickness of the exfoliated
      graphene. Electrochemical decomposition of water into gas bubbles causes the
      expansion of graphite and controls the functionalization and lateral size of the
      exfoliated graphene. Both process steps proceed at different time scales and can
      be individually addressed through application of pulsed voltages. The potential
      of the presented approach was demonstrated by improving the performance of
      graphene-based transparent conductors by 30times. 

PMID- 26221915
TI  - Polypyrrole Microcontainers: Electrochemical Synthesis and Characterization.
AB  - We present electrochemically controlled synthesis of polypyrrole microcontainers
      on electrogenerated hydrogen gas bubbles acting as a template. We performed
      structural characterization of the obtained microcontainers to gain insight into
      the growth kinetics of the polypyrrole shell. Experimental results showed that
      surfactant-mediated polymerization of pyrrole at the hydrogen microbubble surface
      under controlled electrochemical biasing led to the synthesis of various
      micro/nanostructures. Dependent upon the electrochemical conditions, such as the
      number of redox cycles and scan rate, the containers with spherical globules and
      bowl-like structures, which become lantern-like with increasing the number of
      cycles, are formed, as revealed by scanning electron microscopy. Their diameter
      can range between 40 and 200 MUm, and wall thickness can be varied from 2 to 70
      MUm, depending upon the electropolymerization conditions. 

PMID- 26221916
TI  - Efficient Extraction of Trapped Holes from Colloidal CdS Nanorods.
AB  - Cadmium Sulfide (CdS) nanostructures have been widely applied for solar driven H2
      generations due to its suitable band gap and band edge energetics. For an
      efficient photoreduction reaction, hole scavenging from CdS needs to compete
      favorably with many recombination processes. Extensive spectroscopic studies show
      evidence for hole trapping in CdS nanostructures, which naturally leads the
      concern of extracting trapped holes from CdS in photocatalytic reactions. Here,
      we report a study of hole transfer dynamics from colloidal CdS nanorods (NRs) to
      adsorbed hole acceptor, phenothiazine (PTZ), using transient absorption
      spectroscopy. We show that >99% of the holes were trapped (with a time constant
      of 0.73 ps) in free CdS NRs to form a photoinduced transient absorption (PA)
      feature. In the presence of PTZ, we observed the decay of the PA feature and
      corresponding formation of oxidized PTZ(+) radicals, providing direct
      spectroscopic evidence for trapped hole transfer from CdS. The trapped holes were
      extracted by PTZ in 3.8 +/- 1.7 ns (half-life) to form long-lived charge
      separated states (CdS(-)-PTZ(+)) with a half lifetime of 310 +/- 50 ns. This hole
      transfer time is significantly faster than the slow conduction band electron
      trapped hole recombination (half lifetime of 67 +/- 1 ns) in free CdS NRs,
      leading to an extraction efficiency of 94.7 +/- 9.0%. Our results show that
      despite rapid hole trapping in CdS NRs, efficient extraction of trapped holes by
      electron donors and slow recombination of the resulting charge-separated states
      can still be achieved to enable efficient photoreduction using CdS nanocrystals. 

PMID- 26221917
TI  - Who watches the watchmen? How to avoid that valuable use of anti-plagiarism tools
      shift into a witch-hunt.

PMID- 26221918
TI  - The effect of systemic antibiotics administered during the active phase of non
      surgical periodontal therapy or after the healing phase: a systematic review.
AB  - OBJECTIVE: The aim of this systematic review was to compare the clinical
      effectiveness of systemic antibiotics administered in the active stage of
      periodontal treatment or after the healing phase. MATERIAL AND METHODS: An
      electronic search was performed in the databases EMBASE, MEDLINE and Cochrane
      Central Register of Controlled Trials (CENTRAL), in accordance with the Preferred
      Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A
      manual search of the reference list of selected studies and of review articles
      was also performed up to November 2013. Randomized Clinical Trials (RCT) that
      evaluated the systemic administration of antibiotics as adjuvants to scaling and
      root planning (SRP) at different phases of periodontal treatment were included.
      Systematic reviews and studies that evaluated subjects with systemic diseases and
      those that used subantimicrobial doses of antibiotics were excluded. RESULTS: The
      initial search identified 1,039 articles, of which seven were selected, and only
      one met the inclusion criteria. This study showed that subjects taking
      metronidazole and amoxicillin at the initial phase of treatment exhibited
      statistically significantly greater reduction in pocket depth and gain in
      clinical attachment level in initially deep sites (PD>=7 mm) than subjects taking
      antibiotics after healing (p<0.05). This comparison was conducted 2 months after
      antibiotic intake, at the healing phase. CONCLUSION: To date, only one short-term
      RCT has directly compared different moments of systemic antibiotics
      administration, as adjuncts to SRP, in the treatment of periodontitis. Although
      the results of this study suggested some benefits for antibiotics intake during
      the active phase of therapy, these findings need to be confirmed by larger
      placebo-controlled randomized clinical trials with longer follow-up periods.

PMID- 26221919
TI  - Phenotype and cell proliferation activity of duct-like structures in human
      sublingual glands: a histological and immunohistochemical study.
AB  - There are several age-related microscopic changes in the salivary glands,
      including the increase in the number of duct-like structures (DLS). However, the
      true origin and the phenotype of the DLS are not known. OBJECTIVE: To evaluate
      the phenotype and the cell proliferation index of the DLS of human sublingual
      glands. MATERIAL AND METHODS: Sixty sublingual glands obtained from human
      cadavers were divided into two groups - 0-30 and 61-90 years old. The phenotype
      was estimated by immunostaining for cytokeratin 19 (CK 19) and the S-100 protein
      as well as by the presence of mucin and glycogen. The cell proliferation index
      was determined by the Ki-67 antibody. The histochemical techniques used periodic
      acid-Schiff (PAS) and Alcian Blue. In each captured microscopic field, the DLS
      were counted to establish a percentage for the staining profile. The statistical
      analysis was accomplished using Student's t-test, the Mann-Whitney test and
      Pearson's correlation coefficient (p<0.05). RESULTS: Comparing both groups, only
      CK 19 showed a statistically significant difference (p=0.033), with the strongest
      expression in the elderly group. There was no significant difference between PAS
      and Alcian Blue (p=0.270). In both groups, the immunostaining for CK 19 was
      stronger than that for S-100 (p=0.004;p<0.001), but there was no correlation
      between the two immunomarkers (rho=-0.163; p=0.315). There was no immunostaining
      for Ki-67. CONCLUSIONS: DLS demonstrate a ductal phenotypic profile and do not
      present cell proliferation activity. DLS may represent a regressive process
      arising from acini or represent the result of metaplasia.

PMID- 26221920
TI  - MUC-1 expression in pleomorphic adenomas using two human milk fat globule protein
      membrane antibodies (HMFG-1 and HMFG-2).
AB  - Pleomorphic adenoma (PA) is the most common salivary gland tumor and its
      microscopic features and histogenesis are a matter of debate. Human milk fat
      globule protein membrane (HMFG) monoclonal antibodies (MoAbs) comprise a set of
      antibodies against the mucin 1 (MUC-1) protein detected in several salivary gland
      tumors. OBJECTIVE: The aim of this study was to assess the immunoexpression of
      the PA neoplastic cells to MUC-1 protein using HMFG-1 and HMFG-2 MoAbs,
      contrasting these results with those from normal salivary gland tissue. MATERIAL
      AND METHODS: Immunohistochemical detection of MUC-1 protein using HMFG-1 and HMFG
      2 MoAbs was made in 5 mm thick, paraffin embedded slides, and the avidin-biotin
      method was used. RESULTS: Positivity to HMFG-1 and HMFG-2 MoAbs was found in
      ductal, squamous metaplastic and neoplastic myoepithelial cells, keratin pearls
      and intraductal mucous material. Two kinds of myoepithelial cells were
      identified: classic myoepithelial cells around ducts were negative to both MoAbs,
      and modified myoepithelial cells were positive to both MoAbs. This last cellular
      group of the analyzed tumors showed similar MUC-1 immunoexpression to ductal
      epithelial cells using both HMFG antibodies. Intraductal mucous secretion was
      also HMFG-1 and HMFG-2 positive. CONCLUSIONS: Our results showed there are two
      kinds of myoepithelial cells in PA. The first cellular group is represented by
      the different kinds of neoplastic myoepithelial cells and is HMFG-positive. The
      second one is HMFG-negative and represented by the neoplastic myoepithelial cells
      located around the ducts.

PMID- 26221921
TI  - The 19-bp deletion polymorphism of dihydrofolate reductase (DHFR) and
      nonsyndromic cleft lip with or without cleft palate: evidence for a protective
      role.
AB  - OBJECTIVE: Nonsyndromic cleft lip with or without cleft palate (NS-CL/P) are
      among the most common congenital birth defects worldwide. Several lines of
      evidence point to the involvement of folate, as well as folate metabolizing
      enzymes in risk reduction of orofacial clefts. Dihydrofolate reductase (DHFR)
      enzyme participates in the metabolic cycle of folate and has a crucial role in
      DNA synthesis, a fundamental feature of gestation and development. A functional
      polymorphic 19-bp deletion within intron-1 of DHFR has been associated with the
      risk of common congenital malformations. The present study aimed to evaluate the
      possible association between DHFR 19-bp deletion polymorphism and susceptibility
      to NS-CL/P in an Iranian population. MATERIAL AND METHODS: The current study
      recruited 100 NS-CL/P patients and 100 healthy controls. DHFR 19-bp deletion was
      determined using an allele specific-PCR method. RESULTS: We observed the DHFR 19
      bp homozygous deletion genotype (D/D) vs. homozygous wild genotype (WW) was more
      frequent in controls than in NS-CL/P patients (25% vs. 13%), being associated
      with a reduced risk of NS-CL/P in both codominant (OR=0.33, P=0.027) and
      recessive (OR=0.45, P=0.046) tested inheritance models. We also stratified the
      cleft patients and reanalyzed the data. The association trend for CL+CL/P group
      compared to the controls revealed that the DD genotype in both codominant
      (OR=0.30, P=0.032) and recessive models (OR=0.35, P=0.031) was associated with a
      reduced risk of CL+CL/P. CONCLUSIONS: Our results for the first time suggested
      the DHFR 19-bp D/D genotype may confer a reduced risk of NS-CL/P and might act as
      a protective factor against NS-CL/P in the Iranian subjects.

PMID- 26221922
TI  - Early osseointegration driven by the surface chemistry and wettability of dental
      implants.
AB  - OBJECTIVE: The objective of this study was to investigate the impact of two
      different commercially available dental implants on osseointegration. The
      surfaces were sandblasting and acid etching (Group 1) and sandblasting and acid
      etching, then maintained in an isotonic solution of 0.9% sodium chloride (Group
      2). MATERIAL AND METHODS: X-ray photoelectron spectroscopy (XPS) was employed for
      surface chemistry analysis. Surface morphology and topography was investigated by
      scanning electron microscopy (SEM) and confocal microscopy (CM), respectively.
      Contact angle analysis (CAA) was employed for wetting evaluation. Bone-implant
      contact (BIC) and bone area fraction occupied (BAFO) analysis were performed on
      thin sections (30 MUm) 14 and 28 days after the installation of 10 implants from
      each group (n=20) in rabbits' tibias. Statistical analysis was performed by ANOVA
      at the 95% level of significance considering implantation time and implant
      surface as independent variables. RESULTS: Group 2 showed 3-fold less carbon on
      the surface and a markedly enhanced hydrophilicity compared to Group 1 but a
      similar surface roughness (p>0.05). BIC and BAFO levels in Group 2 at 14 days
      were similar to those in Group 1 at 28 days. After 28 days of installation, BIC
      and BAFO measurements of Group 2 were approximately 1.5-fold greater than in
      Group 1 (p<0.05). CONCLUSION: The surface chemistry and wettability implants of
      Group 2 accelerate osseointegration and increase the area of the bone-to-implant
      interface when compared to those of Group 1.

PMID- 26221923
TI  - Comparison of salivary levels of mucin and amylase and their relation with
      clinical parameters obtained from patients with aggressive and chronic
      periodontal disease.
AB  - OBJECTIVE: Salivary mucin and amylase levels are increased in patients with
      chronic periodontitis (CP). Due to the fact that aggressive periodontitis (AgP)
      not only differs from chronic periodontitis in terms of its clinical
      manifestation, the aim of this study was to compare salivary mucin and amylase
      levels and their relation to the clinical parameters of patients with aggressive
      periodontitis with that of patients with chronic periodontitis. MATERIAL AND
      METHODS: Eighty subjects were divided into two groups: 20 patients with AgP and
      their 20 matched controls and 20 patients with CP and their 20 matched controls,
      based on clinical attachment loss (CAL), probing pocket depth (PPD) and bleeding
      on probing (BOP). Whole unstimulated saliva was obtained and mucin, amylase and
      protein were determined by colorimetric methods. Pearson's correlation analysis
      was used to determine the relationship between salivary mucin, amylase and
      protein levels and the clinical parameters. RESULTS: Salivary mucin, amylase and
      protein levels were increased in patients with AgP and CP but there were no
      differences between them or between control groups. Pearson's correlation
      analysis, determined in the entire subjects studied, showed a positive and
      significant correlation of mucin, amylase and proteins with CAL and PPD and a
      negative correlation with the flow rate. When Pearson's correlation analysis was
      carried out in each group separately, Fisher's z transformation showed no
      significant difference between both groups. CONCLUSION: Comparison of the
      salivary levels of mucin, amylase and protein and their relationship with
      clinical parameters of AgP patients with that of CP patients revealed no
      differences between both groups.

PMID- 26221924
TI  - TNF-alpha, TNF-beta and IL-10 gene polymorphism and association with oral lichen
      planus risk in Saudi patients.
AB  - OBJECTIVES: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal
      disease. Cytokines play an important role in the pathogenesis and disease
      progression of OLP. Various reports have implicated cytokine gene polymorphisms
      in susceptibility to develop some immune mediated conditions including OLP. The
      purpose of this study was to investigate the association of tumor necrosis factor
      (TNF)-alpha, TNF-beta and interleukin (IL)-10 gene polymorphisms with the OLP
      risk. MATERIAL AND METHODS: Forty two unrelated patients with OLP and 211 healthy
      volunteers were genotyped for TNF-alpha (-308 G/A), TNF-beta (+252A/G), IL-10 (
      1082G/A), IL-10 (-819C/T), and IL-10 (-592C/A) polymorphisms. RESULTS: The
      frequencies of allele A and genotype GA of TNF-alpha (-308G/A) were significantly
      higher while allele G and GG genotypes were lower in OLP patients as compared to
      the controls (P<0.001). The frequency of GA genotype of TNF-beta (+252A/G) was
      significantly higher in patients than in controls while the AA genotype was
      completely absent in OLP patients. These results indicated that allele A and
      genotype GA of TNF-alpha (-308G/A) as well as the GA genotype of TNF-beta
      (+252A/G) polymorphisms are associated with OLP risk. The frequencies of alleles
      and genotypes of -1082G/A, -819C/T and -592C/A polymorphisms in IL-10 gene did
      not differ significantly between OLP patients and controls (P>0.05). However,
      haplotype ATA extracted from 1082G/A, -819C/T, -592C/A polymorphisms of IL-10
      were more prevalent in OLP patients when compared to controls indicating its
      possible association with OLP susceptibility. CONCLUSION: It is concluded that
      TNF-alpha (-308G/A), TNF-beta (+252A/G) and IL-10 (-1082G/A, -819C/T and -592C/A)
      polymorphisms are associated with the susceptibility of OLP, thus giving
      additional support for the genetic basis of this disease.

PMID- 26221925
TI  - Effectiveness of plant-derived proanthocyanidins on demineralization on enamel
      and dentin under artificial cariogenic challenge.
AB  - Dental caries is considered a disease of high prevalence and a constant problem
      in public health. Proanthocyanidins (PAs) are substances that have been the
      target of recent studies aiming to control or treat caries. OBJECTIVE: The aim of
      this in vitro study was to evaluate the efficacy of a treatment with grape seed
      extract, under cariogenic challenge, to minimize or even prevent the onset of
      caries in the enamel and dentin. MATERIAL AND METHODS: Blocks of enamel and
      dentin (6.0x6.0 mm) were obtained from bovine central incisors, polished, and
      selected by analysis of surface microhardness (SH). The blocks were randomly
      divided into 3 groups (n=15), according to the following treatments: GC
      (control), GSE (grape seed extract), GF (fluoride - 1,000 ppm). The blocks were
      subjected to 6 daily pH cycles for 8 days. Within the daily cycling, the
      specimens were stored in buffered solution. The blocks were then analyzed for
      perpendicular and surface hardness and polarized light microscopy. RESULTS: The
      means were subjected to statistical analysis using the ANOVA and Fisher's PLSD
      tests (p<0.05). For enamel SH, GF showed the highest hardness values. In the
      dentin, GF was also the one that showed higher hardness values, followed by GSE.
      Regarding the cross-sectional hardness values, all groups behaved similarly in
      both the enamel and dentin. The samples that were treated with GSE and fluoride
      (GF) showed statistically higher values than the control. CONCLUSION: Based on
      the data obtained in this in vitro study, it is suggested that grape seed extract
      inhibits demineralization of artificial carious lesions in both the enamel and
      dentin, but in a different scale in each structure and in a smaller scale when
      compared to fluoride.

PMID- 26221926
TI  - Bisphosphonate associated osteomyelitis of the jaw in patients with bony
      exposure: prevention, a new way of thinking.
AB  - Objective There is strong evidence of a link between the use of systemic
      bisphosphonates (BPs) and osteonecrosis of the jaw, especially in cancer
      patients. Among risk factors for BRONJ, tooth extraction and immune suppressive
      drugs seem to have significant role on bone healing. Therefore, the importance of
      these parameters in development of BRONJ was reviewed in this retrospective study
      in two maxillofacial surgery units. Material and Methods From 2007 to 2012, 46
      patients on bisphosphonate who had developed oral bony lesions participated in
      this study. The pharmacological exposure, comorbidities, maxillofacial findings,
      types of treatment and outcome data were collected from clinical and radiological
      records. Results The most frequently used BP was alendronate (67%). Tooth
      extraction was reported in 61% of patients with BRONJ. Systemic corticosteroids
      were prescribed in 35 cases (76%) as an adjuvant for BP. Patients on
      corticosteroids had a lower probability of bony lesion healing (p<0.05) than
      patients without corticosteroids. Of the 46 patients who underwent conservative
      treatments, only ten were completely healed (21%). Conclusions Beside tooth
      extraction, corticosteroids were shown to be an implant risk factor for low rate
      of bone healing and hence the development of BRONJ. The outcome of conservative
      treatment was uncertain and this emphasizes the importance of prevention. 

PMID- 26221927
TI  - Effect of resin-modified glass-ionomer cement lining and composite layering
      technique on the adhesive interface of lateral wall.
AB  - Interface integrity can be maintained by setting the composite in a layering
      technique and using liners. OBJECTIVE: The aim of this in vitro study was to
      verify the effect of resin-modified glass-ionomer cement (RMGIC) lining and
      composite layering technique on the bond strength of the dentin/resin adhesive
      interface of lateral walls of occlusal restorations. MATERIAL AND METHODS:
      Occlusal cavities were prepared in 52 extracted sound human molars, randomly
      assigned into 4 groups: Group 2H (control) - no lining + two horizontal layers;
      Group 4O: no lining + four oblique layers; Group V-2H: RMGIC lining (Vitrebond) +
      two horizontal layers; and Group V-4O: RMGIC lining (Vitrebond) + four oblique
      layers. Resin composite (Filtek Z250, 3M ESPE) was placed after application of an
      adhesive system (AdperTM Single Bond 2, 3M ESPE) dyed with a fluorescent reagent
      (Rhodamine B) to allow confocal microscopy analysis. The teeth were stored in
      deionized water at 37oC for 24 hours before being sectioned into 0.8 mm slices.
      One slice of each tooth was randomly selected for Confocal Laser Scanning
      Microscopy (CLSM) analysis. The other slices were sectioned into 0.8 mm x 0.8 mm
      sticks to microtensile bond strength test (MPa). Data were analyzed by two-way
      ANOVA and Fisher's test. Results There was no statistical difference on bond
      strength among groups (p>0.05). CLSM analysis showed no significant statistical
      difference regarding the presence of gap at the interface dentin/resin among
      groups. CONCLUSIONS: RMGIC lining and composite layering techniques showed no
      effect on the microtensile bond strength and gap formation at the adhesive
      interface of lateral walls of high C-factor occlusal restorations.

PMID- 26221928
TI  - Mechanical, antibacterial and bond strength properties of nano-titanium-enriched
      glass ionomer cement.
AB  - The use of nanoparticles (NPs) has become a significant area of research in
      Dentistry. Objective The aim of this study was to investigate the physical,
      antibacterial activity and bond strength properties of conventional base, core
      build and restorative of glass ionomer cement (GIC) compared to GIC supplemented
      with titanium dioxide (TiO2) nanopowder at 3% and 5% (w/w). Material and Methods
      Vickers microhardness was estimated with diamond indenter. Compressive and
      flexural strengths were analyzed in a universal testing machine. Specimens were
      bonded to enamel and dentine, and tested for shear bond strength in a universal
      testing machine. Specimens were incubated with S. mutans suspension for
      evaluating antibacterial activity. Surface analysis of restorative conventional
      and modified GIC was performed with SEM and EDS. The analyses were carried out
      with Kolmogorov-Smirnov, ANOVA (post-hoc), Tukey test, Kruskal-Wallis, and Mann
      Whitney. Results Conventional GIC and GIC modified with TiO2 nanopowder for the
      base/liner cement and core build showed no differences for mechanical,
      antibacterial, and shear bond properties (p>0.05). In contrast, the
      supplementation of TiO2 NPs to restorative GIC significantly improved Vickers
      microhardness (p<0.05), flexural and compressive strength (p<0.05), and
      antibacterial activity (p<0.001), without interfering with adhesion to enamel and
      dentin. Conclusion GIC supplemented with TiO2 NPs (FX-II) is a promising material
      for restoration because of its potential antibacterial activity and durable
      restoration to withstand the mastication force. 

PMID- 26221930
TI  - Polymeric biomaterials for cancer nanotechnology.

PMID- 26221931
TI  - Lipid-coated polymeric nanoparticles for cancer drug delivery.
AB  - Polymeric nanoparticles and liposomes have been the platform of choice for
      nanoparticle-based cancer drug delivery applications over the past decade, but
      extensive research has revealed their limitations as drug delivery carriers. A
      hybrid class of nanoparticles, aimed at combining the advantages of both
      polymeric nanoparticles and liposomes, has received attention in recent years.
      These core/shell type nanoparticles, frequently referred to as lipid-polymer
      hybrid nanoparticles (LPNs), possess several characteristics that make them
      highly suitable for drug delivery. This review introduces the formulation methods
      used to synthesize LPNs and discusses the strategies used to treat cancer, such
      as by targeting the tumor microenvironment or vasculature. Finally, it discusses
      the challenges that must be overcome to realize the full potential of LPNs in the
      clinic. 

PMID- 26221932
TI  - Supramolecular hydrogels: synthesis, properties and their biomedical
      applications.
AB  - As a novel class of three-dimensional (3D) hydrophilic cross-linked polymers,
      supramolecular hydrogels not only display unique physicochemical properties
      (e.g., water-retention ability, drug loading capacity, biodegradability and
      biocompatibility, biostability) as well as specific functionalities (e.g.,
      optoelectronic properties, bioactivity, self-healing ability, shape memory
      ability), but also have the capability to undergo reversible gel-sol transition
      in response to various environmental stimuli inherent to the noncovalent cross
      linkages, thereby showing great potential as promising biomaterial scaffolds for
      diagnosis and therapy. In this Review, we summarized the recent progress in the
      design and synthesis of supramolecular hydrogels through specific, directional
      noncovalent interactions, with particular emphasis on the structure-property
      relationship, as well as their wide-ranging applications in disease diagnosis and
      therapy including bioimaging, biodetection, therapeutic delivery, and tissue
      engineering. We believe that these current achievements in supramolecular
      hydrogels will greatly stimulate new ideas and inspire persistent efforts in this
      hot topic area in future. 

PMID- 26221933
TI  - Trigger responsive polymeric nanocarriers for cancer therapy.
AB  - Conventional chemotherapy for the treatment of cancer has limited specificity
      when administered systemically and is often associated with toxicity issues.
      Enhanced accumulation of polymeric nanocarriers at a tumor site may be achieved
      by passive and active targeting. Incorporation of trigger responsiveness into
      these polymeric nanocarriers improves the anticancer efficacy of such systems by
      modulating the release of the drug according to the tumor environment. Triggers
      used for tumor targeting include internal triggers such as pH, redox and enzymes
      and external triggers such as temperature, magnetic field, ultrasound and light.
      While internal triggers are specific cues of the tumor microenvironment, external
      triggers are those which are applied externally to control the release. This
      review highlights the various strategies employed for the preparation of such
      trigger responsive polymeric nanocarriers for cancer therapy and provides an
      overview of the state of the art in this field. 

PMID- 26221934
TI  - Emerging antitumor applications of extracellularly reengineered polymeric
      nanocarriers.
AB  - Recently, polymeric nanocarriers with shielding surfaces, e.g., poly(ethylene
      glycol) and small molecules, have been widely applied in antitumor drug delivery
      mainly because of their stealth during blood circulation. However, the shielding
      shell greatly hinders the tumor penetration, drug release, and cell
      internalization of the nanocarriers, which leads to unsatisfactory therapeutic
      efficacy. To integrate the extended blood circulation time and the enhanced drug
      transmission in one platform, some extracellularly stimuli-mediated shell
      sheddable polymeric nanocarriers have been exploited. The systems are stealthy
      and stable during blood circulation, and as soon as they reach tumor tissue, the
      shielding matrices are removed, which is triggered by extracellular endogenous
      stimuli (e.g., pH or enzymes) or exogenous excitations (e.g., light or voltage).
      This review mainly focuses on recent advances in the designs and emerging
      antitumor applications of extracellularly reengineered polymeric nanocarriers for
      directional drug delivery, as well as perspectives for future developments. 

PMID- 26221929
TI  - Host response mechanisms in periodontal diseases.
AB  - Periodontal diseases usually refer to common inflammatory disorders known as
      gingivitis and periodontitis, which are caused by a pathogenic microbiota in the
      subgingival biofilm, including Porphyromonas gingivalis, Aggregatibacter
      actinomycetemcomitans, Tannerella forsythia and Treponema denticola that trigger
      innate, inflammatory, and adaptive immune responses. These processes result in
      the destruction of the tissues surrounding and supporting the teeth, and
      eventually in tissue, bone and finally, tooth loss. The innate immune response
      constitutes a homeostatic system, which is the first line of defense, and is able
      to recognize invading microorganisms as non-self, triggering immune responses to
      eliminate them. In addition to the innate immunity, adaptive immunity cells and
      characteristic cytokines have been described as important players in the
      periodontal disease pathogenesis scenario, with a special attention to CD4+ T
      cells (T-helper cells). Interestingly, the T cell-mediated adaptive immunity
      development is highly dependent on innate immunity-associated antigen presenting
      cells, which after antigen capture undergo into a maturation process and migrate
      towards the lymph nodes, where they produce distinct patterns of cytokines that
      will contribute to the subsequent polarization and activation of specific T CD4+
      lymphocytes. Skeletal homeostasis depends on a dynamic balance between the
      activities of the bone-forming osteoblasts (OBLs) and bone-resorbing osteoclasts
      (OCLs). This balance is tightly controlled by various regulatory systems, such as
      the endocrine system, and is influenced by the immune system, an
      osteoimmunological regulation depending on lymphocyte- and macrophage-derived
      cytokines. All these cytokines and inflammatory mediators are capable of acting
      alone or in concert, to stimulate periodontal breakdown and collagen destruction
      via tissue-derived matrix metalloproteinases, a characterization of the
      progression of periodontitis as a stage that presents a significantly host immune
      and inflammatory response to the microbial challenge that determine of
      susceptibility to develop the destructive/progressive periodontitis under the
      influence of multiple behavioral, environmental and genetic factors. 

PMID- 26221935
TI  - Polymeric biomaterials for the delivery of platinum-based anticancer drugs.
AB  - Since cisplatin, cis-diamminedichloroplatinum(ii), received FDA approval for use
      in cancer treatment in 1978, platinum-based drugs have been one of the most
      widely used drugs for the treatment of tumors in testicles, ovaries, head and
      neck. However, there are concerns associated with the use of platinum-based
      anticancer drugs, owing to severe side effects and drug resistance. In order to
      overcome these limitations, various drug-delivery systems have been developed
      based on diverse organic and inorganic materials. In particular, the versatility
      of polymeric materials facilitates the tuning of drug-delivery systems to meet
      their primary goals. This review focuses on the progress made over the last five
      years in the application of polymeric nanoparticles for the delivery of platinum
      based anticancer drugs. The present article not only describes the fundamental
      principles underlying the implementation of polymeric nanomaterials in platinum
      based drug delivery, but also summarizes concepts and strategies employed in the
      development of drug-delivery systems. 

PMID- 26221936
TI  - Engineering DNA scaffolds for delivery of anticancer therapeutics.
AB  - Engineering DNA nanostructures with programmability in size, shape and surface
      chemistry holds tremendous promise in biomedical applications. As an emerging
      platform for drug delivery, DNA nanostructures have been extensively studied for
      delivering anticancer therapeutics, including small-molecule drug, nucleic acids
      and proteins. In this mini-review, current advances in utilizing DNA scaffolds as
      drug carriers for cancer treatment were summarized and future challenges were
      also discussed. 

PMID- 26221938
TI  - Drug and gene co-delivery systems for cancer treatment.
AB  - Cancer remains a major killer and a leading cause of death in the world; thus, a
      growing number of new treatments have been focused on cancer therapy over the
      past few decades. Chemotherapy, which is thought to be a powerful strategy for
      cancer treatment, has been widely used in clinical therapy in recent years.
      However, due to the complexity of cancer, a single therapeutic approach is
      insufficient for the suppression of cancer growth and migration. Therefore,
      increasing attention has been paid to the use of smart multifunctional carriers
      and combinatorially delivers chemotherapeutic drugs and functional genes in order
      to maximize therapeutic efficiency. Combination therapy using selected drugs and
      genes can not only overcome multidrug resistance and inhibit the cellular anti
      apoptotic process but also achieve a synergistic therapeutic effect. Because
      multifunctional nanocarriers are important for achieving these goals, this review
      will illustrate and discuss some advanced biomaterial nanocarriers for co
      delivering therapeutic genes and drugs, including multifunctional micelles,
      liposomes, polymeric conjugates and inorganic nanoparticles. In addition, the
      challenges and future perspectives for co-delivery systems, containing
      therapeutic drugs and genes to achieve better therapeutic effects for cancer
      treatment will be discussed. 

PMID- 26221937
TI  - Recent advances in targeted drug delivery approaches using dendritic polymers.
AB  - Since they were first synthesized over 30 years ago, dendrimers have seen rapid
      translation into various biomedical applications. A number of reports have not
      only demonstrated their clinical utility, but also revealed novel design
      approaches and strategies based on the elucidation of underlying mechanisms
      governing their biological interactions. This review focuses on presenting the
      latest advances in dendrimer design, discussing the current mechanistic
      understandings, and highlighting recent developments and targeted approaches
      using dendrimers in drug/gene delivery. 

PMID- 26221939
TI  - Cyclodextrin-functionalized polymers as drug carriers for cancer therapy.
AB  - Cyclodextrins (CDs) represent the most extensively investigated cyclic molecules
      due to their wide availability, facile functionalization, unique amphiphilicity
      and inclusion capacity. The marriage of CD chemistry with polymer science has
      generated novel biomaterials by integrating supermolecular host-guest chemistry
      and state-of-the-art polymer chemistry techniques. The current mini-review
      focuses on the recent progress in CD-functionalized polymers as drug carriers for
      cancer therapy. CD-functionalized polymers with different structures are
      summarized. Their application as drug carriers for cancer therapy is then
      highlighted. In the end, the future directions of this rapidly developing
      research field are discussed. 

PMID- 26221940
TI  - Polymeric assembly of hyperbranched building blocks to establish tunable
      nanoplatforms for lysosome acidity-responsive gene/drug co-delivery.
AB  - This study plans to develop a nanoparticle technology that can assemble different
      polymeric "building blocks" with various desired functionalities into one
      nanosystem in a pH-dependent manner. For this purpose, polymeric building blocks
      were specifically designed with hyperbranched architectures, and orthogonal pH
      reversible phenylboronic acid-diols were taken as "joints" to integrate them
      together. To verify the idea, a corona-core dual-polymer nanoassembly was
      prepared as the vehicle for lysosomotropic gene/drug co-delivery. Phenylboronic
      acid modified hyperbranched oligoethylenimine (OEI-PBA) was arranged to cluster
      around the hydrophobic core composed of hyperbranched polyglycerol, just by
      mixing two polymers in an appropriate ratio at neutral conditions. Compared with
      the parent OEI-PBA, this nanoassembly demonstrated better capture of plasmid DNA,
      highly enhanced activity for cellular transport and gene transfection (up to 100
      fold), the ability to further load hydrophobic drugs, lysosome acidity-targeting
      pH-dependent release of both carried cargoes, and improved cell-biocompatibility.
      To evaluate its potential for combinational gene/drug therapy, in vitro
      experiments using the therapeutic p53 gene and antitumor doxorubicin as models
      were carried out. This intracellular co-delivery led to apparently synergetic
      anti-cancer effects in cultured cancer cells. This dynamic paradigm shows
      interesting features including easy manipulation, reversible conjugation,
      lysosome-targeting pH-responsiveness, high co-delivery efficiency, and functional
      expandability by further accommodating other building blocks. 

PMID- 26221941
TI  - Well-defined diblock brush polymer-drug conjugates for sustained delivery of
      paclitaxel.
AB  - Using the 3(rd) generation Grubbs' catalyst as the initiator, diblock brush
      polymer drug conjugates (BPDCs) were synthesized by sequential ring-opening
      metathesis polymerization (ROMP) of a hydrophilic poly(ethylene glycol) (PEG)
      based norbornene (NB)-functionalized macromonomer and a hydrophobic paclitaxel
      (PTXL)-based NB-functionalized monomer. These amphiphilic diblock BPDCs had well
      defined structures, with narrow molecular weight distributions (Mw/Mn = 1.10
      1.16). They self-assembled into multi-molecular nanostructures in aqueous
      solutions. Although the PTXL moieties were connected to the backbone with
      cycloacetal-based conjugation linkages, the cleavage of these linkages from the
      assemblies of diblock BPDCs was relatively slow and exhibited limited acid
      sensitivity, indicating a significant influence of the macromolecular structure
      and assembly of BPDCs on their drug release behaviour. The cytotoxicity study not
      only showed that the diblock BPDCs are therapeutically effective against cancer
      cells, but also revealed a correlation between cytotoxicity and grafting
      structures of BPDCs. In summary, the results obtained in this work provide new
      insight into the structure-dependent properties of brush polymer-based drug
      delivery systems. 

PMID- 26221942
TI  - Enhanced transcellular penetration and drug delivery by crosslinked polymeric
      micelles into pancreatic multicellular tumor spheroids.
AB  - Many attempts have been made in the application of multicellular tumor spheroids
      (MCTS) as a 3D tumor model to investigate their biological responses upon
      introduction of polymeric micelles as nanocarriers for therapeutic applications.
      However, the micelle penetration pathways in MCTS are not yet known. In this
      study, micelles (uncrosslinked, UCM) were prepared by self-assembly of block
      copolymer poly(N-(2-hydroxypropyl) methacrylamide-co-methacrylic acid)-block
      poly(methyl methacrylate) (P(HPMA-co-MAA)-b-PMMA). Subsequently, the shells were
      crosslinked to form relatively stable micelles (CKM). Both UCM and CKM penetrated
      deeper and delivered more doxorubicin (DOX) into MCTS than the diffusion of the
      free DOX. Additionally, CKM revealed higher delivery efficiency than UCM. The
      inhibition of caveolae-mediated endocytosis, by Filipin treatment, decreased the
      uptake and penetration of the micelles into MCTS. Treatment with Exo1, an
      exocytosis inhibitor, produced the same effect. Furthermore, movement of the
      micelles through the extracellular matrices (ECM), as modelled using collagen
      micro-spheroids, appeared to be limited to the peripheral layer of the collagen
      spheroids. Those results indicate that penetration of P(HPMA-co-MAA)-b-PMMA
      micelles depended more on transcellular transport than on diffusion through ECM
      between the cells. DOX-loaded CKM inhibited MCTS growth more than their UCM
      counterpart, due to possible cessation of endocytosis and exocytosis in the
      apoptotic peripheral cells, caused by faster release of DOX from UCM. 

PMID- 26221943
TI  - Enhanced tumor-targeted gene delivery by bioreducible polyethylenimine tethering
      EGFR divalent ligands.
AB  - This work demonstrates successful delivery of a gene to EGFR-overexpressed cancer
      cells by using a rationally designed branched GE11 peptide as a targeting ligand.
      In addition, we exploited the effect of the divalent structure of the branched
      GE11 peptide on the gene delivery and tumor targeting efficiency, compared to the
      monovalent GE11 peptide. The GE11 or branched GE11-tethered polymers were
      successfully synthesized. They are composed of a targeting peptide, disulfide
      crosslinked low molecular weight polyethylenimine and polyethylene glycol. Here,
      we evaluated the physicochemical properties, cytotoxicity and in vitro
      transfection efficiency and in vivo biodistribution of the GE11 and branched GE11
      tethered polyplexes. Our results demonstrated that GE11 and bGE11-tethered gene
      delivery carriers showed efficient gene condensing ability, an enhanced
      transfection efficiency and targeting ability with low cytotoxicity.
      Interestingly, the branched GE11-tethered polymer showed the greater targeting
      ability to EGFR-overexpressed cancer cells in vivo than the GE11-tethered
      polymer. Therefore, this branched structure of targeting ligand has the potential
      for providing a novel strategy to design an efficient targeted delivery system. 

PMID- 26221944
TI  - A block copolymer of zwitterionic polyphosphoester and polylactic acid for drug
      delivery.
AB  - Polymeric nanoparticles have been widely used as nano-drug delivery systems in
      preclinical and clinical trials for cancer therapy, and these systems usually
      need to be sterically stabilized by poly(ethylene glycol) (PEG) to maintain
      stability and avoid rapid clearance by the immune system. Recently, zwitterionic
      materials have been demonstrated to be potential alternatives to the classic PEG.
      Herein, we developed two drug delivery systems stabilized by zwitterionic
      polyphosphoesters. These nanoparticles showed favourable stability and anti
      protein absorption ability in vitro. Meanwhile, as drug carriers, these
      zwitterionic polyphosphoester-stabilized nanoparticles significantly prolonged
      drug circulation half-lives and increased drug accumulation in tumors, which was
      comparable to PEG-stabilized nanoparticles. Systemic delivery of doxorubicin
      (DOX) by zwitterionic polyphosphoester-stabilized nanoparticles significantly
      inhibited tumor growth in a MDA-MB-231 tumor model, suggesting the potential of
      zwitterionic polyphosphoester-based nanoparticles in anticancer drug delivery. 

PMID- 26221945
TI  - Mixing-sequence-dependent nucleic acid complexation and gene transfer efficiency
      by polyethylenimine.
AB  - Polyplexes, complexed nucleic acids by cationic polymers, are the most common
      forms of nonviral gene delivery vectors. In contrast to a great deal of efforts
      in synthesizing novel cationic polymers and exploring their extracellular and
      intracellular delivery pathways, polyplex preparation methods of mixing nucleic
      acids and cationic polymers are often overlooked. In this study, the mixing
      sequence, that is adding nucleic acids to polymers or vice versa, was found to
      greatly affect complexation of both plasmid DNA and siRNA, polyplexes' size, and
      polyplexes' surface charge, which all collaboratively affected the transfection
      efficiency and cytotoxicity. Adding polyethylenimine (PEI), the most
      conventionally used standard in nonviral gene delivery, to plasmid DNA and siRNA
      resulted in larger polyplexes, higher gene expression and silencing, but higher
      cytotoxicity than polyplexes prepared in the reverse order. Based on the
      experimental results, the authors developed a model that gradual addition of
      cationic polymers (e.g., PEI) to nucleic acids (e.g., plasmid DNA and siRNA)
      incorporates more copies of nucleic acids in larger polyplexes in a smaller
      number, results in higher gene expression and silencing levels in transfected
      cells, and generates higher cytotoxicity by leaving more free polymers upon
      complete mixing than the other mixing sequence. The proposed model can be
      explored using a broad range of cationic polymers and nucleic acids, and provide
      insightful information about how to prepare polyplexed nonviral vectors for
      efficient and safe gene delivery. 

PMID- 26221946
TI  - Reductively degradable alpha-amino acid-based poly(ester amide)-graft-galactose
      copolymers: facile synthesis, self-assembly, and hepatoma-targeting doxorubicin
      delivery.
AB  - Novel reductively degradable alpha-amino acid-based poly(ester amide)-graft
      galactose (SSPEA-Gal) copolymers were designed and developed to form smart nano
      vehicles for active hepatoma-targeting doxorubicin (DOX) delivery. SSPEA-Gal
      copolymers were readily synthesized via solution polycondensation reaction of di
      p-toluenesulfonic acid salts of bis-l-phenylalanine 2,2-thiodiethanol diester and
      bis-vinyl sulfone functionalized cysteine hexanediol diester with dinitrophenyl
      ester of adipic acid, followed by conjugating with thiol-functionalized galactose
      (Gal-SH) via the Michael addition reaction. SSPEA-Gal formed unimodal
      nanoparticles (PDI = 0.10 - 0.12) in water, in which average particle sizes
      decreased from 138 to 91 nm with increasing Gal contents from 31.6 wt% to 42.5
      wt%. Notably, in vitro drug release studies showed that over 80% DOX was released
      from SSPEA-Gal nanoparticles within 12 h under an intracellular mimicking
      reductive conditions, while low DOX release (<20%) was observed for reduction
      insensitive PEA-Gal nanoparticles under otherwise the same conditions and SSPEA
      Gal nanoparticles under non-reductive conditions. Notably, SSPEA-Gal
      nanoparticles exhibited high specificity to asialoglycoprotein receptor (ASGP-R)
      overexpressing HepG2 cells. MTT assays using HepG2 cells showed that DOX-loaded
      SSPEA-Gal had a low half maximal inhibitory concentration (IC50) of 1.37 MUg mL(
      1), approaching that of free DOX. Flow cytometry and confocal laser scanning
      microscopy studies confirmed the efficient uptake of DOX-loaded SSPEA-Gal
      nanoparticles by HepG2 cells as well as fast intracellular DOX release.
      Importantly, SSPEA-Gal and PEA-Gal nanoparticles were non-cytotoxic to HepG2 and
      MCF-7 cells up to a tested concentration of 1.0 mg mL(-1). These tumor-targeting
      and reduction-responsive degradable nanoparticles have appeared as an interesting
      multi-functional platform for advanced drug delivery. 

PMID- 26221947
TI  - Near-infrared light-triggered drug release nanogels for combined photothermal
      chemotherapy of cancer.
AB  - Near-infrared (NIR) light-triggered drug release systems are promising for drug
      delivery applications in view of the advantages of NIR light, which include high
      tissue penetration and low damage. In this report, we developed nanogels (NGs) by
      supramolecular self-assembly from adamantine (AD)-conjugated copolymer,
      poly[poly(ethylene glycol)monomethyl ether metharcylate]-co-poly(N-(2
      hydroxypropyl)methacrylamide)-co-poly(N-adamantan-1-yl-2-methacrylamide) (PPEGMA
      co-PHPMA-co-PADMA), and beta-cyclodextrin (beta-CD)-functionalized
      poly(amidoamine) (PAMAM) dendrimer based on the host-guest interaction of the AD
      and beta-CD moieties, and they were used to encapsulate indocyanine green (ICG)
      and doxorubicin (DOX) for combined photothermal-chemotherapy. NGs simultaneously
      loading ICG and DOX (DINGs) showed significant photothermal effects and stimuli
      triggered drug release under NIR laser irradiation by the photothermal-induced
      relaxation or dissociation of the NGs. In vitro cytotoxicity evaluation of DINGs
      under NIR irradiation demonstrated the synergistic effects of hyperthermia,
      photothermal-triggered drug release, and chemotherapy. In vivo investigation
      revealed their high accumulation in tumor tissue and significant tumor growth
      suppression under NIR irradiation. These NIR light-triggered drug release NGs
      represent efficient and promising anticancer drug vectors for the combined
      photothermal-chemotherapy of cancer to maximize therapeutic efficacy and minimize
      side effects. 

PMID- 26221948
TI  - Follow-Up Genotoxic Study: Chromosome Damage Two and Six Years after Exposure to
      the Prestige Oil Spill.
AB  - BACKGROUND: The north-west coast of Spain was heavily contaminated by the
      Prestige oil spill, in 2002. Individuals who participated in the clean-up tasks
      showed increased chromosome damage two years after exposure. Long-term clinical
      implications of chromosome damage are still unknown. OBJECTIVE: To realize a
      follow-up genotoxic study to detect whether the chromosome damage persisted six
      years after exposure to the oil. DESIGN: Follow-up study. SETTING: Fishermen
      cooperatives in coastal villages. PARTICIPANTS: Local fishermen who were highly
      exposed (n = 52) and non-exposed (n = 23) to oil seven years after the spill.
      MEASUREMENTS: Chromosome damage in circulating lymphocytes. RESULTS: Chromosome
      damage in exposed individuals persists six years after oil exposure, with a
      similar incidence than those previously detected four years before. A surprising
      increase in chromosome damage in non-exposed individual was found six years after
      Prestige spill vs. those detected two years after the exposure. LIMITATIONS: The
      sample size and the possibility of some kind of selection bias should be
      considered. Genotoxic results cannot be extrapolated to the approximately 300,000
      individuals who participated occasionally in clean-up tasks. CONCLUSION: The
      persistence of chromosome damage detected in exposed individuals six years after
      oil exposure seems to indicate that the cells of the bone marrow are affected. A
      surprising increase in chromosome damage in non-exposed individuals detected in
      the follow-up study suggests an indirect exposition of these individuals to some
      oil compounds or to other toxic agents during the last four years. More long-term
      studies are needed to confirm the presence of chromosome damage in exposed and
      non-exposed fishermen due to the association between increased chromosomal damage
      and increased risk of cancer. Understanding and detecting chromosome damage is
      important for detecting cancer in its early stages. The present work is the first
      follow-up cytogenetic study carried out in lymphocytes to determine genotoxic
      damage evolution between two and six years after oil exposure in same
      individuals.

PMID- 26221950
TI  - Assessment of Coastal Ecosystem Services for Conservation Strategies in South
      Korea.
AB  - Despite the fact that scientific and political consideration for ecosystem
      services has dramatically increased over the past decade, few studies have
      focused on marine and coastal ecosystem services for conservation strategies. We
      used an ecosystem services approach to assess spatial distributions of habitat
      risks and four ecosystem services (coastal protection, carbon storage,
      recreation, and aesthetic quality), and explored the tradeoffs among them in
      coastal areas of South Korea. Additionally, we analyzed how the social and
      ecological characteristics in coastal areas interact with conservation and
      development policies by using this approach. We found strong negative
      associations between the habitat risks and ecosystem services (aquaculture,
      carbon storage, recreation, and aesthetic quality) across the coastal counties.
      Our results showed that the intensity of the habitat risks and the provision of
      ecosystem services were significantly different between reclamation-dominated and
      conservation-dominated counties, except for coastal vulnerability. A generalized
      linear model suggested that reclamation projects were dependent on economic
      efficiency, whereas demographic pressures and habitat conditions influenced the
      designation of protected areas at a county level. The ecosystem services approach
      provided guidelines to achieve both sustainable development and environment
      conservation. By using the approach, we can select the priority areas for
      developments while we can minimize the degradation of biodiversity and ecosystem
      services. As cultural ecosystem services are evenly distributed throughout
      coastal areas of South Korea, decision makers may employ them to improve the
      conditions of coastal wetlands outside of protected areas. 

PMID- 26221949
TI  - Secondary Structure of Rat and Human Amylin across Force Fields.
AB  - The aggregation of human amylin has been strongly implicated in the progression
      of Type II diabetes. This 37-residue peptide forms a variety of secondary
      structures, including random coils, alpha-helices, and beta-hairpins. The balance
      between these structures depends on the chemical environment, making amylin an
      ideal candidate to examine inherent biases in force fields. Rat amylin differs
      from human amylin by only 6 residues; however, it does not form fibrils.
      Therefore it provides a useful complement to human amylin in studies of the key
      events along the aggregation pathway. In this work, the free energy of rat and
      human amylin was determined as a function of alpha-helix and beta-hairpin content
      for the Gromos96 53a6, OPLS-AA/L, CHARMM22/CMAP, CHARMM22*, Amberff99sb*-ILDN,
      and Amberff03w force fields using advanced sampling techniques, specifically bias
      exchange metadynamics. This work represents a first systematic attempt to
      evaluate the conformations and the corresponding free energy of a large,
      clinically relevant disordered peptide in solution across force fields. The NMR
      chemical shifts of rIAPP were calculated for each of the force fields using their
      respective free energy maps, allowing us to quantitatively assess their
      predictions. We show that the predicted distribution of secondary structures is
      sensitive to the choice of force-field: Gromos53a6 is biased towards beta
      hairpins, while CHARMM22/CMAP predicts structures that are overly alpha-helical.
      OPLS-AA/L favors disordered structures. Amberff99sb*-ILDN, AmberFF03w and
      CHARMM22* provide the balance between secondary structures that is most
      consistent with available experimental data. In contrast to previous reports, our
      findings suggest that the equilibrium conformations of human and rat amylin are
      remarkably similar, but that subtle differences arise in transient alpha-helical
      and beta-strand containing structures that the human peptide can more readily
      adopt. We hypothesize that these transient states enable dynamic pathways that
      facilitate the formation of aggregates and, eventually, amyloid fibrils. 

PMID- 26221951
TI  - Viability of Booby Offspring is Maximized by Having One Young Parent and One Old
      Parent.
AB  - It is widely expected that the quality of offspring will vary with the age of
      their parents and that this variation should influence animals' choice of mates.
      However, theoretical predictions for age effects are contradictory and, to our
      knowledge, we do not know for any wild animal how the quality of offspring is
      affected by both parents' ages across their lifespans, or whether mothers' and
      fathers' ages interact. We tackled this question using long-term data on a highly
      philopatric, insular population of the blue-footed booby (Sula nebouxii). In this
      species extra-pair paternity is most common in pairs of two young parents or two
      old parents, implying that these age combinations might prejudice offspring
      quality. Analysis of the viability of 3,361 offspring of parents up to 21 years
      old revealed that fledglings with two young parents or two old parents were least
      likely to become breeders, whereas fledglings with one young parent and one old
      parent were most likely to do so. For young parents of either sex, offspring
      viability increased with age of the other parent; for very old parents, it
      decreased. These effects could be mediated by parents flexibly modifying their
      investment in offspring in response to their own and their partners' ages, but
      evidence for this was lacking. In 5,343 breeding attempts, although mothers' and
      fathers' ages independently affected four heavily care-dependent breeding traits
      at the clutch and nestling stages, their interaction did not affect any trait.
      The effects of parental age combinations on viability could also be mediated by
      genes: fledglings with one young parent and one old parent could benefit from
      greater heterozygosity or better genes. 

PMID- 26221952
TI  - Prospectively ECG-Triggered Sequential Dual-Source Coronary CT Angiography in
      Patients with Atrial Fibrillation: Influence of Heart Rate on Image Quality and
      Evaluation of Diagnostic Accuracy.
AB  - OBJECTIVES: To evaluate the effects of mean heart rate (HR) and heart rate
      variation (HRV) on image quality and diagnostic accuracy of prospectively ECG
      triggered sequential dual-source coronary CT angiography (CCTA) in patients with
      atrial fibrillation (AF). METHODS: Eighty-five patients (49 women, 36 men; mean
      age 62. 1 +/- 9.5 years) with persistent AF underwent prospectively ECG-triggered
      sequential second-generation dual-source CCTA. Tube current and voltage were
      adjusted according to body mass index (BMI) and iterative reconstruction was
      used. Image quality of coronary segments (four-point scale) and presence of
      significant stenosis (>50%) were evaluated. Diagnostic accuracy was analyzed in
      30 of the 85 patients who underwent additional invasive coronary angiography
      (ICA). RESULTS: Only 8 of 1102 (0.7%) segments demonstrated poor image quality.
      No significant impact on image quality was found for mean HR (94.9 +/- 21.8 bpm;
      r=0.034, p=0.758; F=0.413, p=0.663) or HRV (67.5 +/- 22.8 bpm; r=0.097, p=0.377;
      F=0.111, p=0.895). On per-segment analysis, sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV) were 89.7% (26/29),
      99.4% (355/357), 92.9% (26/28), and 99.2% (355/358), respectively, with excellent
      correlation (kappa=0.91) with ICA. Mean effective dose was 3.3 +/- 1.0 mSv.
      CONCLUSIONS: Prospectively ECG-triggered sequential dual-source CCTA provides
      diagnostic image quality and good diagnostic accuracy for detection of coronary
      stenosis in AF patients without significant influence by HR or HRV.

PMID- 26221953
TI  - A TALEN-Exon Skipping Design for a Bethlem Myopathy Model in Zebrafish.
AB  - Presently, human collagen VI-related diseases such as Ullrich congenital muscular
      dystrophy (UCMD) and Bethlem myopathy (BM) remain incurable, emphasizing the need
      to unravel their etiology and improve their treatments. In UCMD, symptom onset
      occurs early, and both diseases aggravate with ageing. In zebrafish fry,
      morpholinos reproduced early UCMD and BM symptoms but did not allow to study the
      late phenotype. Here, we produced the first zebrafish line with the human
      mutation frequently found in collagen VI-related disorders such as UCMD and BM.
      We used a transcription activator-like effector nuclease (TALEN) to design the
      col6a1ama605003-line with a mutation within an essential splice donor site, in
      intron 14 of the col6a1 gene, which provoke an in-frame skipping of exon 14 in
      the processed mRNA. This mutation at a splice donor site is the first example of
      a template-independent modification of splicing induced in zebrafish using a
      targetable nuclease. This technique is readily expandable to other organisms and
      can be instrumental in other disease studies. Histological and ultrastructural
      analyzes of homozygous and heterozygous mutant fry and 3 months post
      fertilization (mpf) fish revealed co-dominantly inherited abnormal myofibers with
      disorganized myofibrils, enlarged sarcoplasmic reticulum, altered mitochondria
      and misaligned sarcomeres. Locomotion analyzes showed hypoxia-response behavior
      in 9 mpf col6a1 mutant unseen in 3 mpf fish. These symptoms worsened with ageing
      as described in patients with collagen VI deficiency. Thus, the col6a1ama605003
      line is the first adult zebrafish model of collagen VI-related diseases; it will
      be instrumental both for basic research and drug discovery assays focusing on
      this type of disorders. 

PMID- 26221954
TI  - Brain Amyloid Deposition and Longitudinal Cognitive Decline in Nondemented Older
      Subjects: Results from a Multi-Ethnic Population.
AB  - OBJECTIVE: We aimed to whether the abnormally high amyloid-beta (Abeta) level in
      the brain among apparently healthy elders is related with subtle cognitive
      deficits and/or accelerated cognitive decline. METHODS: A total of 116 dementia
      free participants (mean age 84.5 years) of the Washington Heights Inwood Columbia
      Aging Project completed 18F-Florbetaben PET imaging. Positive or negative
      cerebral Abeta deposition was assessed visually. Quantitative cerebral Abeta
      burden was calculated as the standardized uptake value ratio in pre-established
      regions of interest using cerebellar cortex as the reference region. Cognition
      was determined using a neuropsychological battery and selected tests scores were
      combined into four composite scores (memory, language, executive/speed, and
      visuospatial) using exploratory factor analysis. We examined the relationship
      between cerebral Abeta level and longitudinal cognition change up to 20 years
      before the PET scan using latent growth curve models, controlling for age,
      education, ethnicity, and Apolipoprotein E (APOE) genotype. RESULTS: Positive
      reading of Abeta was found in 41 of 116 (35%) individuals. Cognitive scores at
      scan time was not related with Abeta. All cognitive scores declined over time.
      Abeta positive reading (B = -0.034, p = 0.02) and higher Abeta burden in temporal
      region (B = -0.080, p = 0.02) were associated with faster decline in
      executive/speed. Stratified analyses showed that higher Abeta deposition was
      associated with faster longitudinal declines in mean cognition, language, and
      executive/speed in African-Americans or in APOE epsilon4 carriers, and with
      faster memory decline in APOE epsilon4 carriers. The associations remained
      significant after excluding mild cognitive impairment participants. CONCLUSIONS:
      High Abeta deposition in healthy elders was associated with decline in
      executive/speed in the decade before neuroimaging, and the association was
      observed primarily in African-Americans and APOE epsilon4 carriers. Our results
      suggest that measuring cerebral Abeta may give us important insights into the
      cognitive profile in the years prior to the scan in cognitively normal elders.

PMID- 26221955
TI  - No Clear Association between Impaired Short-Term or Working Memory Storage and
      Time Reproduction Capacity in Adult ADHD Patients.
AB  - OBJECTIVE: Altered time reproduction is exhibited by patients with adult
      attention deficit hyperactivity disorder (ADHD). It remains unclear whether
      memory capacity influences the ability of adults with ADHD to reproduce time
      intervals. METHOD: We conducted a behavioral study on 30 ADHD patients who were
      medicated with methylphenidate, 29 unmedicated adult ADHD patients and 32 healthy
      controls (HCs). We assessed time reproduction using six time intervals (1 s, 4 s,
      6 s, 10 s, 24 s and 60 s) and assessed memory performance using the Wechsler
      memory scale. RESULTS: The patients with ADHD exhibited lower memory performance
      scores than the HCs. No significant differences in the raw scores for any of the
      time intervals (p > .05), with the exception of the variability at the short time
      intervals (1 s, 4 s and 6 s) (p < .01), were found between the groups. The
      overall analyses failed to reveal any significant correlations between time
      reproduction at any of the time intervals examined in the time reproduction task
      and working memory performance (p > .05). CONCLUSION: We detected no findings
      indicating that working memory might influence time reproduction in adult
      patients with ADHD. Therefore, further studies concerning time reproduction and
      memory capacity among adult patients with ADHD must be performed to verify and
      replicate the present findings.

PMID- 26221956
TI  - Transcriptome Profiling of Wild-Type and pga-Knockout Mutant Strains Reveal the
      Role of Exopolysaccharide in Aggregatibacter actinomycetemcomitans.
AB  - Exopolysaccharides have a diverse set of functions in most bacteria including a
      mechanistic role in protecting bacteria against environmental stresses. Among the
      many functions attributed to the exopolysaccharides, biofilm formation,
      antibiotic resistance, immune evasion and colonization have been studied most
      extensively. The exopolysaccharide produced by many Gram positive as well as Gram
      negative bacteria including the oral pathogen Aggregatibacter
      actinomycetemcomitans is the homopolymer of beta(1,6)-linked N-acetylglucosamine.
      Recently, we reported that the PGA-deficient mutant of A. actinomycetemcomitans
      failed to colonize or induce bone resorption in a rat model of periodontal
      disease, and the colonization genes, apiA and aae, were significantly down
      regulated in the mutant strain. To understand the role of exopolysaccharide and
      the pga locus in the global expression of A. actinomycetemcomitans, we have used
      comparative transcriptome profiling to identify differentially expressed genes in
      the wild-type strain in relation to the PGA-deficient strain. Transcriptome
      analysis revealed that about 50% of the genes are differently expressed (P < 0.05
      and fold change >1.5). Our study demonstrated that the absence of the pga locus
      affects the genes involved in peptidoglycan recycling, glycogen storage, and
      virulence. Further, using confocal microscopy and plating assays, we show that
      the viability of pga mutant strain is significantly reduced during biofilm
      growth. Thus, this study highlights the importance of pga genes and the
      exopolysaccharide in the virulence of A. actinomycetemcomitans. 

PMID- 26221957
TI  - Diversity, Bacterial Symbionts and Antibacterial Potential of Gut-Associated
      Fungi Isolated from the Pantala flavescens Larvae in China.
AB  - The diversity of fungi associated with the gut of Pantala flavescens larvae was
      investigated using a culture-dependent method and molecular identification based
      on an analysis of the internally transcribed spacer sequence. In total, 48 fungal
      isolates were obtained from P. flavescens larvae. Based on phylogenetic analyses,
      the fungal isolates were grouped in 5 classes and 12 different genera. Fourteen
      bacterial 16S rDNA sequences derived from total genomic DNA extractions of fungal
      mycelia were obtained. The majority of the sequences were associated with
      Proteobacteria (13/14), and one Bacillaceae (1/14) was included. Leclercia sp.,
      Oceanobacillus oncorhynchi and Methylobacterium extorquens, were reported for the
      first time as bacterial endosymbionts in fungi. High-performance liquid
      chromatography (HPLC) analysis indicated that bacterial symbionts produced
      specific metabolites and also exerted an inhibitory effect on fungal metabolites.
      The biological activity of the fungal culture extracts against the pathogenic
      bacteria Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6633) and
      Escherichia coli (ATCC 8739) was investigated, and 20 extracts (42%) exhibited
      antibacterial activity against at least one of the tested bacterial strains. This
      study is the first report on the diversity and antibacterial activity of
      symbiotic fungi residing in the gut of P. flavescens larvae, and the results show
      that these fungi are highly diverse and could be exploited as a potential source
      of bioactive compounds. 

PMID- 26221958
TI  - Spatial Structure of Evolutionary Models of Dialects in Contact.
AB  - Phylogenetic models, originally developed to demonstrate evolutionary biology,
      have been applied to a wide range of cultural data including natural language
      lexicons, manuscripts, folktales, material cultures, and religions. A fundamental
      question regarding the application of phylogenetic inference is whether trees are
      an appropriate approximation of cultural evolutionary history. Their validity in
      cultural applications has been scrutinized, particularly with respect to the
      lexicons of dialects in contact. Phylogenetic models organize evolutionary data
      into a series of branching events through time. However, branching events are
      typically not included in dialectological studies to interpret the distributions
      of lexical terms. Instead, dialectologists have offered spatial interpretations
      to represent lexical data. For example, new lexical items that emerge in a
      politico-cultural center are likely to spread to peripheries, but not vice versa.
      To explore the question of the tree model's validity, we present a simple
      simulation model in which dialects form a spatial network and share lexical items
      through contact rather than through common ancestors. We input several network
      topologies to the model to generate synthetic data. We then analyze the
      synthesized data using conventional phylogenetic techniques. We found that a
      group of dialects can be considered tree-like even if it has not evolved in a
      temporally tree-like manner but has a temporally invariant, spatially tree-like
      structure. In addition, the simulation experiments appear to reproduce unnatural
      results observed in reconstructed trees for real data. These results motivate
      further investigation into the spatial structure of the evolutionary history of
      dialect lexicons as well as other cultural characteristics. 

PMID- 26221959
TI  - Computational Approaches for Decoding Select Odorant-Olfactory Receptor
      Interactions Using Mini-Virtual Screening.
AB  - Olfactory receptors (ORs) belong to the class A G-Protein Coupled Receptor
      superfamily of proteins. Unlike G-Protein Coupled Receptors, ORs exhibit a
      combinatorial response to odors/ligands. ORs display an affinity towards a range
      of odor molecules rather than binding to a specific set of ligands and conversely
      a single odorant molecule may bind to a number of olfactory receptors with
      varying affinities. The diversity in odor recognition is linked to the highly
      variable transmembrane domains of these receptors. The purpose of this study is
      to decode the odor-olfactory receptor interactions using in silico docking
      studies. In this study, a ligand (odor molecules) dataset of 125 molecules was
      used to carry out in silico docking using the GLIDE docking tool (SCHRODINGER Inc
      Pvt LTD). Previous studies, with smaller datasets of ligands, have shown that
      orthologous olfactory receptors respond to similarly-tuned ligands, but are
      dramatically different in their efficacy and potency. Ligand docking results were
      applied on homologous pairs (with varying sequence identity) of ORs from human
      and mouse genomes and ligand binding residues and the ligand profile differed
      among such related olfactory receptor sequences. This study revealed that
      homologous sequences with high sequence identity need not bind to the same/
      similar ligand with a given affinity. A ligand profile has been obtained for each
      of the 20 receptors in this analysis which will be useful for expression and
      mutation studies on these receptors. 

PMID- 26221960
TI  - Population Genetics of Franciscana Dolphins (Pontoporia blainvillei): Introducing
      a New Population from the Southern Edge of Their Distribution.
AB  - Due to anthropogenic factors, the franciscana dolphin, Pontoporia blainvillei, is
      the most threatened small cetacean on the Atlantic coast of South America. Four
      Franciscana Management Areas have been proposed: Espiritu Santo to Rio de Janeiro
      (FMA I), Sao Paulo to Santa Catarina (FMA II), Rio Grande do Sul to Uruguay (FMA
      III), and Argentina (FMA IV). Further genetic studies distinguished additional
      populations within these FMAs. We analyzed the population structure,
      phylogeography, and demographic history in the southernmost portion of the
      species range. From the analysis of mitochondrial DNA control region sequences, 5
      novel haplotypes were found, totalizing 60 haplotypes for the entire distribution
      range. The haplotype network did not show an apparent phylogeographical signal
      for the southern FMAs. Two populations were identified: Monte Hermoso (MH) and
      Necochea (NC)+Claromeco (CL)+Rio Negro (RN). The low levels of genetic
      variability, the relative constant size over time, and the low levels of gene
      flow may indicate that MH has been colonized by a few maternal lineages and
      became isolated from geographically close populations. The apparent increase in
      NC+CL+RN size would be consistent with the higher genetic variability found,
      since genetic diversity is generally higher in older and expanding populations.
      Additionally, RN may have experienced a recent split from CL and NC; current high
      levels of gene flow may be occurring between the latter ones. FMA IV would
      comprise four franciscana dolphin populations: Samborombon West+Samborombon
      South, Cabo San Antonio+Buenos Aires East, NC+CL+Buenos Aires Southwest+RN and
      MH. Results achieved in this study need to be taken into account in order to
      ensure the long-term survival of the species. 

PMID- 26221961
TI  - An Internally Translated MAVS Variant Exposes Its Amino-terminal TRAF-Binding
      Motifs to Deregulate Interferon Induction.
AB  - Activation of pattern recognition receptors and proper regulation of downstream
      signaling are crucial for host innate immune response. Upon infection, the NF
      kappaB and interferon regulatory factors (IRF) are often simultaneously activated
      to defeat invading pathogens. Mechanisms concerning differential activation of NF
      kappaB and IRF are not well understood. Here we report that a MAVS variant
      inhibits interferon (IFN) induction, while enabling NF-kappaB activation.
      Employing herpesviral proteins that selectively activate NF-kappaB signaling, we
      discovered that a MAVS variant of ~50 kDa, thus designated MAVS50, was produced
      from internal translation initiation. MAVS50 preferentially interacts with TRAF2
      and TRAF6, and activates NF-kappaB. By contrast, MAVS50 inhibits the IRF
      activation and suppresses IFN induction. Biochemical analysis showed that MAVS50,
      exposing a degenerate TRAF-binding motif within its N-terminus, effectively
      competed with full-length MAVS for recruiting TRAF2 and TRAF6. Ablation of the
      TRAF-binding motif of MAVS50 impaired its inhibitory effect on IRF activation and
      IFN induction. These results collectively identify a new means by which signaling
      events is differentially regulated via exposing key internally embedded
      interaction motifs, implying a more ubiquitous regulatory role of truncated
      proteins arose from internal translation and other related mechanisms. 

PMID- 26221962
TI  - Blood Pressure Control Has Improved in People with and without Type 2 Diabetes
      but Remains Suboptimal: A Longitudinal Study Based on the German DIAB-CORE
      Consortium.
AB  - BACKGROUND: Hypertension is a very common comorbidity and major risk factor for
      cardiovascular complications, especially in people with Type 2 Diabetes (T2D).
      Nevertheless, studies in the past have shown that blood pressure is often
      insufficiently controlled in medical practice. For the DIAB-CARE study, we used
      longitudinal data based on the German DIAB-CORE Consortium to assess whether
      health care regarding hypertension has improved during the last decade in our
      participants. METHODS: Data of the three regional population-based studies CARLA
      (baseline 2002-2006 and follow-up 2007-2010), KORA (baseline 1999-2001 and follow
      up 2006-2008) and SHIP (baseline 1997-2001 and follow-up 2002-2006) were pooled.
      Stratified by T2D status we analysed changes in frequencies, degrees of
      awareness, treatment and control. Linear mixed models were conducted to assess
      the influence of sex, age, study, and T2D status on changes of systolic blood
      pressure between the baseline and follow-up examinations (mean observation time
      5.7 years). We included 4,683 participants aged 45 to 74 years with complete data
      and accounted for 1,256 participants who were lost to follow-up by inverse
      probability weighting. RESULTS: Mean systolic blood pressure decreased in all
      groups from baseline to follow-up (e.g. - 8.5 mmHg in those with incident T2D).
      Pulse pressure (PP) was markedly higher in persons with T2D than in persons
      without T2D (64.14 mmHg in prevalent T2D compared to 52.87 mmHg in non-T2D at
      baseline) and did not change much between the two examinations. Awareness,
      treatment and control increased considerably in all subgroups however, the
      percentage of those with insufficiently controlled hypertension remained high (at
      about 50% of those with hypertension) especially in prevalent T2D. Particularly
      elderly people with T2D often had both, high blood pressure >=140/90 mmHg and a
      PP of >=60 mmHg. Blood pressure in men had improved more than in women at follow
      up, however, men still had higher mean SBP than women at follow-up. CONCLUSION:
      Blood pressure management has developed positively during past years in Germany.
      While hypertension prevalence, awareness and treatment were substantially higher
      in participants with T2D than in those without T2D at follow-up, hypertension
      control was achieved only in about half the number of people in each T2D group
      leaving much room for further improvement.

PMID- 26221963
TI  - Predictive Factors for BRCA1 and BRCA2 Genetic Testing in an Asian Clinic-Based
      Population.
AB  - PURPOSE: The National Comprehensive Cancer Network (NCCN) has proposed guidelines
      for the genetic testing of the BRCA1 and BRCA2 genes, based on studies in western
      populations. This current study assessed potential predictive factors for BRCA
      mutation probability, in an Asian population. METHODS: A total of 359 breast
      cancer patients, who presented with either a family history (FH) of breast and/or
      ovarian cancer or early onset breast cancer, were accrued at the National Cancer
      Center Singapore (NCCS). The relationships between clinico-pathological features
      and mutational status were calculated using the Chi-squared test and binary
      logistic regression analysis. RESULTS: Of 359 patients, 45 (12.5%) had
      deleterious or damaging missense mutations in BRCA1 and/or BRCA2. BRCA1 mutations
      were more likely to be found in ER-negative than ER-positive breast cancer
      patients (P=0.01). Moreover, ER-negative patients with BRCA mutations were
      diagnosed at an earlier age (40 vs. 48 years, P=0.008). Similarly, triple
      negative breast cancer (TNBC) patients were more likely to have BRCA1 mutations
      (P=0.001) and that these patients were diagnosed at a relatively younger age than
      non-TNBC patients (38 vs. 46 years, P=0.028). Our analysis has confirmed that ER
      negative status, TNBC status and a FH of hereditary breast and ovarian cancer
      (HBOC) are strong factors predicting the likelihood of having BRCA mutations.
      CONCLUSIONS: Our study provides evidence that TNBC or ER-negative patients may
      benefit from BRCA genetic testing, particularly younger patients (<40 years) or
      those with a strong FH of HBOC, in Asian patients.

PMID- 26221965
TI  - The acid adaptive tolerance response in Campylobacter jejuni induces a global
      response, as suggested by proteomics and microarrays.
AB  - Campylobacter jejuni CI 120 is a natural isolate obtained during poultry
      processing and has the ability to induce an acid tolerance response (ATR) to acid
      + aerobic conditions in early stationary phase. Other strains tested they did not
      induce an ATR or they induced it in exponential phase. Campylobacter spp. do not
      contain the genes that encode the global stationary phase stress response
      mechanism. Therefore, the aim of this study was to identify genes that are
      involved in the C. jejuni CI 120 early stationary phase ATR, as it seems to be
      expressing a novel mechanism of stress tolerance. Two-dimensional gel
      electrophoresis was used to examine the expression profile of cytosolic proteins
      during the C. jejuni CI 120 adaptation to acid + aerobic stress and microarrays
      to determine the genes that participate in the ATR. The results indicate
      induction of a global response that activated a number of stress responses,
      including several genes encoding surface components and genes involved with iron
      uptake. The findings of this study provide new insights into stress tolerance of
      C. jejuni, contribute to a better knowledge of the physiology of this bacterium
      and highlight the diversity among different strains. 

PMID- 26221966
TI  - A novel continuous colour mapping approach for visualization of facial skin
      hydration and transepidermal water loss for four ethnic groups.
AB  - OBJECTIVES: The aim of this exploratory study was to develop a novel colour
      mapping approach to visualize and interpret the complexity of facial skin
      hydration and barrier properties of four ethnic groups (Caucasians, Indians,
      Chinese and Black Africans) living in Pretoria, South Africa. METHODS: We
      measured transepidermal water loss (TEWL) and skin capacitance on 30 pre-defined
      sites on the forehead, cheek, jaw and eye areas of sixteen women (four per ethnic
      group) and took digital images of their faces. Continuous colour maps were
      generated by interpolating between each measured value and superimposing the
      values on the digital images. RESULTS: The complexity of facial skin hydration
      and skin barrier properties is revealed by these measurements and visualized by
      the continuous colour maps of the digital images. Overall, the Caucasian subjects
      had the better barrier properties followed by the Black African subjects, Chinese
      subjects and Indian subjects. Nevertheless, the two more darkly pigmented ethnic
      groups had superior skin hydration properties. Subtle differences were seen when
      examining the different facial sites. CONCLUSIONS: There exists remarkable skin
      capacitance and TEWL gradients within short distances on selected areas of the
      face. These gradients are distinctive in the different ethnic groups. In contrast
      to other reports, we found that darkly pigmented skin does not always have a
      superior barrier function and differences in skin hydration values are complex on
      the different parts of the face among the different ethnic groups.

PMID- 26221964
TI  - Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional
      Signatures.
AB  - Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in
      numerous species. Physiological responses to CR are cell-type specific and
      variable throughout the lifespan. However, the mosaic of molecular changes
      responsible for CR benefits remains unclear, particularly in brain regions
      susceptible to deterioration during aging. We examined the influence of long-term
      CR on the CA1 hippocampal region, a key learning and memory brain area that is
      vulnerable to age-related pathologies, such as Alzheimer's disease (AD). Through
      mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of
      CR feeding suppresses age-dependent signatures of 882 genes functionally
      associated with synaptic transmission-related pathways, including calcium
      signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By
      comparing the influence of CR on hippocampal CA1 region transcriptional profiles
      at younger-adult (5 months, 2.5 months of feeding) and older-adult (15 months,
      12.5 months of feeding) timepoints, we identify conserved upregulation of
      proteome quality control and calcium buffering genes, including heat shock 70 kDa
      protein 1b (Hspa1b) and heat shock 70 kDa protein 5 (Hspa5), protein disulfide
      isomerase family A member 4 (Pdia4) and protein disulfide isomerase family A
      member 6 (Pdia6), and calreticulin (Calr). Expression levels of putative
      neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated
      by CR in adulthood, although the global CR-specific expression profiles at
      younger and older timepoints are highly divergent. At a previously unachieved
      resolution, our results demonstrate conserved activation of neuroprotective gene
      signatures and broad CR-suppression of age-dependent hippocampal CA1 region
      expression changes, indicating that CR functionally maintains a more youthful
      transcriptional state within the hippocampal CA1 sector. 

PMID- 26221967
TI  - An In Vivo 24-Month Study to Compare Crestal Bone Loss and Pocket Depth of
      Platform-Switched Implants Placed in Maxillary Anterior and Mandibular Posterior
      Regions.
AB  - PURPOSE: To analyze and compare crestal bone loss and pocket depth around
      platform-switched implants placed at two intraoral locations. MATERIALS AND
      METHODS: Eighty platform-switched implants, 40 in the maxillary anterior region
      (group - ANT) and 40 in the mandibular posterior region (group - POST), were
      placed in healthy men aged between 25 and 45 years, and restored following two
      stage surgical and progressive loading protocols. Digital radiographs for crestal
      bone level assessment and pocket depths on facial, mesial, distal, and
      palatal/lingual sites around the implant were recorded at definitive restoration
      cementation (baseline) and 6-month follow-up. Difference in pre- and post
      periodontal pocket depths and crestal bone loss levels were measured and analyzed
      statistically using SPSS v.16.0, applying the Mann-Whitney test (p < 0.05
      considered significant). RESULTS: Mean bone loss was significantly higher in
      group ANT (1.2 +/- 0.3 mm) than in group POST (0.7 +/- 0.02 mm). Palatal pocket
      depth increase was significantly greater in the ANT group (p = 0.01), and distal
      pocket depth increase was significantly greater for the POST group (p = 0.002).
      CONCLUSION: The amount of bone loss noted in the maxillary anterior region
      compared to the mandibular posterior region was significantly more. This could
      possibly be because of greater vertical cantilever and offset loads in the
      anterior compared to the posterior region. Significantly greater pocket depth in
      mandibular posterior distal and maxillary anterior palatal regions could be
      related to oral hygiene maintenance issues.

PMID- 26221968
TI  - Mitotane treatment in patients with adrenocortical cancer causes central
      hypothyroidism.
AB  - INTRODUCTION: Mitotane, a steroidogenesis inhibitor with adrenolytic properties
      used to treat adrenocortical cancer (ACC), can affect thyroid function. A
      reduction of FT4 levels with normal FT3 and TSH has been described in these
      patients. Using an in vitro murine model, the secretory capacity of thyrotrophic
      cells has been shown to be inhibited by mitotane. OBJECTIVE: To investigate the
      pathogenesis of thyroid abnormalities in mitotane-treated patients with ACC.
      PATIENTS AND METHODS: In five female patients with ACC (median age 47; range 31
      65) treated with mitotane (dosage 1.5 g/day; 1.0-3.0), we analysed the pattern of
      TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age-
      and gender-matched control group. The in vivo secretory activity of the
      thyrotrophic cells was evaluated using a standard TRH test (200 MUg), and the
      response was compared to both a group of age-matched female controls (n = 10) and
      central hypothyroid patients (n = 10). RESULTS: Basal TSH (median 1.54 mU/l;
      range 1.20-2.17) was normal and scattered around our median reference value, FT3
      levels (median 3.80 pmol/l; 3.30-4.29) were normal but below the median reference
      value of 4.37 pmol/l and FT4 levels were below the normal range in all patients
      (median 8.40 pmol/l; 7.6-9.9). FT3/FT4 ratio was in the upper range in 4 patients
      and higher than normal in one patient. A blunted TSH response to TRH was observed
      in mitotane-treated patients. DeltaTSH (absolute TSH response, peak TSH minus
      basal TSH) was 3.65 (range 3.53-5.26), 12.37 (range 7.55-19.97) and 1.32 mU/l
      (range 0.52-4.66) in mitotane-treated patients, controls and central hypothyroid
      patients, respectively. PRL secretion was normal. CONCLUSIONS: Mitotane-treated
      patients with ACC showed low FT4, normal FT3 and TSH and impaired TSH response to
      TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4
      ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a
      compensatory mechanism characteristic of thyroid function changes observed in
      hypothyroid conditions. This finding thus confirms in vitro studies and may have
      a therapeutic implication for treatment with thyroid hormones, as suggested by
      current guidelines for this specific condition.

PMID- 26221970
TI  - Anti-angiogenic effect of ALS-L1023, an extract of Melissa officinalis L., on
      experimental choroidal neovascularization in mice.
AB  - BACKGROUND: The effect of ALS-L1023, an extract of Melissa officinalis L.
      (Labiatae; lemon balm) leaves, on experimental choroidal neovascularization (CNV)
      in mice was evaluated. METHODS: C57BL/6 mice were given either vehicle or ALS
      L1023 daily via oral gavage for 3 weeks (days 0-21). CNV was induced by rupturing
      Bruch's membrane using laser photocoagulation (day 7). Two weeks after laser
      injury (day 21), the CNV lesions were evaluated by an examination of choroidal
      flat mounts using fluorescein-labelled dextran, immunofluorescence staining with
      isolectin B4 and fluorescence angiography. The effects of ALS-L1023 on
      endothelial cell tube formation and the expression of phosphorylated
      extracellular signal-regulated kinase 1/2 were evaluated using human umbilical
      vein endothelial cells. RESULTS: The extent of CNV was reduced by ALS-L1023. Mice
      treated with 100 and 200 mg/kg/day of the material exhibited 44.3 and 68.1%
      reductions in the extent of CNV lesions, respectively, compared to the vehicle
      group (P < 0.001). The size of the isolectin B4-labelled area was also
      significantly decreased in the ALS-L1023-treated groups (P < 0.001). On
      fluorescein angiography, ALS-L1023-treated mice exhibited significantly less
      leakage of fluorescent material than did vehicle-treated mice. ALS-L1023
      decreased vascular endothelial growth factor-induced human umbilical vein
      endothelial cell tube formation in a dose-dependent manner. The expression of
      phosphorylated extracellular signal-regulated kinase 1/2 was suppressed by ALS
      L1023. CONCLUSIONS: The laser-induced CNV in mice can be inhibited by ALS-L1023.
      Therefore, it may have therapeutic potential for the treatment of diseases
      involving CNV.

PMID- 26221969
TI  - The association between state bans on soda only and adolescent substitution with
      other sugar-sweetened beverages: a cross-sectional study.
AB  - BACKGROUND: Across the United States, many states have actively banned the sale
      of soda in high schools, and evidence suggests that students' in-school access to
      soda has declined as a result. However, schools may be substituting soda with
      other sugar-sweetened beverages (SSBs), and national trends indicate that
      adolescents are consuming more sports drinks and energy drinks. This study
      examined whether students consumed more non-soda SSBs in states that banned the
      sale of soda in school. METHODS: Student data on consumption of various SSBs and
      in-school access to vending machines that sold SSBs were obtained from the
      National Youth Physical Activity and Nutrition Study (NYPANS), conducted in 2010.
      Student data were linked to state laws regarding the sale of soda in school in
      2010. Students were cross-classified based on their access to vending machines
      and whether their state banned soda in school, creating 4 comparison groups. Zero
      inflated negative binomial models were used to compare these 4 groups with
      respect to students' self-reported consumption of diet soda, sports drinks,
      energy drinks, coffee/tea, or other SSBs. Students who had access to vending
      machines in a state that did not ban soda were the reference group. Models were
      adjusted for race/ethnicity, sex, grade, home food access, state median income,
      and U.S. Census region. RESULTS: Students consumed more servings of sports
      drinks, energy drinks, coffee/tea, and other SSBs if they resided in a state that
      banned soda in school but attended a school with vending machines that sold other
      SSBs. Similar results were observed where schools did not have vending machines
      but the state allowed soda to be sold in school. Intake was generally not
      elevated where both states and schools limited SSB availability - i.e., states
      banned soda and schools did not have SSB vending machines. CONCLUSION: State laws
      that ban soda but allow other SSBs may lead students to substitute other non-soda
      SSBs. Additional longitudinal research is needed to confirm this. Elevated SSB
      intake was not observed when both states and schools took steps to remove SSBs
      from school.

PMID- 26221971
TI  - Time to redefine Myeloma.
AB  - In November 2014 the International Myeloma Working Group (IMWG) revised the
      definition of multiple myeloma, such that asymptomatic patients with newly
      diagnosed multiple myeloma without any of the traditional 'CRAB' (hypercalcaemia,
      renal impairment, anaemia, bone disease) end organ damage criteria but with one
      of three new criteria would be recommended to start treatment. Previously, the
      standard of care for such patients was expectant management. These three new
      criteria are: greater than 60% clonal plasma cells on bone marrow biopsy, a serum
      free light chain (sFLC) ratio of >100 (the involved sFLC must be >100 mg/l) and
      greater than one unequivocal focal lesion on advanced imaging (low dose whole
      body computerized tomography, magnetic resonance imaging, (18) F
      fluorodeoxyglucose positron emission tomography). Although this would appear to
      affect a small number of patients, the impact of these changes are broad, leading
      to an increased use of advanced imaging, a debate around the management of
      patients previously diagnosed with smouldering myeloma, changed terminology and
      clinical trial design and an extension of the use of biomarkers. For the first
      time the philosophy of treatment in myeloma will change from treatment initiation
      only being triggered by overt end organ damage to an era where sub clinical risk
      factors will also be taken into account. 

PMID- 26221972
TI  - A polymorphism in a phosphotyrosine signalling motif of CD229 (Ly9, SLAMF3)
      alters SH2 domain binding and T-cell activation.
AB  - Signalling lymphocyte activation molecule (SLAM) family members regulate
      activation and inhibition in the innate and adaptive immune systems. Genome-wide
      association studies identified their genetic locus (1q23) as highly polymorphic
      and associated with susceptibility to systemic lupus erythematosus (SLE). Here we
      show that the Val602 variant of the non-synonymous single nucleotide polymorphism
      (SNP) rs509749 in the SLAM family member CD229 (Ly9, SLAMF3) has a two-fold lower
      affinity compared with the SLE-associated Met602 variant for the small adaptor
      protein SAP. Comparison of the two variants in T-cell lines revealed the Val602
      variant to be significantly more highly expressed than CD229 Met602 . Activation
      was diminished in cells expressing CD229 Val602 compared with CD229 Met602 as
      measured by up-regulation of CD69. There was no correlation between homozygosity
      at rs509749 and activation in peripheral blood mononuclear cells from healthy
      donors. These findings identify potential mechanisms by which a single SNP can
      perturb fine-tuning in the immune system with significant functional
      consequences. 

PMID- 26221973
TI  - Envelopment-Internalization Synergistic Effects and Metabolic Mechanisms of
      Graphene Oxide on Single-Cell Chlorella vulgaris Are Dependent on the
      Nanomaterial Particle Size.
AB  - The interactions between nanomaterials and cells are fundamental in biological
      responses to nanomaterials. However, the size-dependent synergistic effects of
      envelopment and internalization as well as the metabolic mechanisms of
      nanomaterials have remained unknown. The nanomaterials tested here were larger
      graphene oxide nanosheets (GONS) and small graphene oxide quantum dots (GOQD).
      GONS intensively entrapped single-celled Chlorella vulgaris, and envelopment by
      GONS reduced the cell permeability. In contrast, GOQD-induced remarkable
      shrinkage of the plasma membrane and then enhanced cell permeability through
      strong internalization effects such as plasmolysis, uptake of nanomaterials, an
      oxidative stress increase, and inhibition of cell division and chlorophyll
      biosynthesis. Metabolomics analysis showed that amino acid metabolism was
      sensitive to nanomaterial exposure. Shrinkage of the plasma membrane is proposed
      to be linked to increases in the isoleucine levels. The inhibition of cell
      division and chlorophyll a biosynthesis was associated with decreases in aspartic
      acid and serine, the precursors of chlorophyll a. The increases in mitochondrial
      membrane potential loss and oxidative stress were correlated with an increase in
      linolenic acid. The above metabolites can be used as indicators of the
      corresponding biological responses. These results enhance our systemic
      understanding of the size-dependent biological effects of nanomaterials. 

PMID- 26221974
TI  - Decoherence Allows Model Reduction in Nonadiabatic Dynamics Simulations.
AB  - A nonadiabatic (NA) molecular dynamics (MD) simulation requires calculation of NA
      coupling matrix elements, the number of which scales as a square of the number of
      basis states. The basis size can be huge in studies of nanoscale materials, and
      calculation of the NA couplings can present a significant bottleneck. A quantum
      classical approximation, NAMD overestimates coherence in the quantum, electronic
      subsystem, requiring decoherence correction. Generally, decoherence times
      decrease with increasing energy separation between pairs of states forming
      coherent superpositions. Since rapid decoherence stops quantum dynamics, one
      expects that decoherence-corrected NAMD can eliminate the need for calculation of
      NA couplings between energetically distant states, notably reducing the
      computational cost. Considering several types of dynamics in a semiconductor
      quantum dot, we demonstrate that indeed, decoherence allows one to reduce the
      number of needed NA coupling matrix elements. If the energy levels are spaced
      closer than 0.1 eV, one obtains good results while including only three nearest
      neighbor couplings, and in some cases even with just the first nearest-neighbor
      coupling scheme. If the energy levels are spaced by about 0.4 eV, the nearest
      neighbor model fails, while three or more nearest-neighbor schemes also provide
      good results. In comparison, the results of NAMD simulation without decoherence
      vary continuously with changes in the number of NA couplings. Thus, decoherence
      effects induced by coupling to a quantum-mechanical environment not only provide
      the physical mechanism for NAMD trajectory branding and improve the accuracy of
      NAMD simulations, but also afford significant computational savings. 

PMID- 26221975
TI  - Endovascular treatment of traumatic rupture of thoracic aorta: long term results.
AB  - BACKGROUND: The aim of this study was to evaluate the endovascular treatment of
      acute post-traumatic thoracic aorta rupture. Rupture of the thoracic aorta is
      caused in a majority of cases by blunt trauma of the chest as a result of motor
      vehicle accident. Hypovolemic shock due to massive hemorrhage leads to death in
      almost 90% of victims. Nowadays the treatment of choice is endovascular procedure
      with stent-graft, which quickly seals the rupture site. METHODS: Forty patients
      with post-traumatic rupture were treated in our department. In 92.5% of them, the
      aneurysm appeared after a road traffic accident. In all cases but one it was
      located below the left subclavian artery. RESULTS: All patients underwent
      surgery. One-hundred per cent technical success was observed with no device
      failure. Six patients (15%) died in the postoperative period. All fatalities were
      attributable to severe generalized trauma, not to the endovascular procedure. In
      early postoperative follow-up we saw no serious stent-graft related
      complications, such as spinal cord ischemia. Nine patients (22.5%) were operated
      later on, due to other organs trauma. In one case (2.5%), in which the endograft
      was deployed below the left subclavian artery, the patient suffered from stroke,
      requiring conservative treatment. One early type IA endoleak was diagnosed and
      sealed by proximal extension. Among the patients still being followed for up to
      14 years, 82% remain asymptomatic, without evidence of endoleak or stent-graft
      migration on angio-CT. Two type IA endoleak were found due to stent-graft
      infolding: one was solved with balloon-plasty, the other with a proximal
      extension. CONCLUSIONS: Endovascular procedure in traumatic rupture of descending
      aorta is the method of choice. Endovascular procedures have a lower mortality and
      morbidity than open surgery.

PMID- 26221976
TI  - Immediate and long-term outcomes of endovascular treatment for massive
      hemoptysis.
AB  - BACKGROUND: The aim of this study was to evaluate the immediate and long-term
      outcomes of endovascular treatment for massive hemoptysis and to identify the
      factors influencing outcome. METHODS: A total of 147 patients who underwent
      transarterial embolization for massive hemoptysis between 2001 and 2012 were
      retrospectively evaluated. All patients (93 males and 54 females, ranging in age
      from 28 to 76 years) had active massive bleeding and underwent bronchial artery
      embolization (BAE) and/or non-bronchial artery embolization (NBAE). Angiography
      result, endovascular techniques, embolized materials and complications were
      recorded. RESULTS: Complete cessation of massive hemoptysis was achieved in
      126/147 patients (85.7%) and failed in 21/147 patients (14.3%) within 24 hours.
      The etiology of hemoptysis was as follows: bronchiectasis (49.7%), tuberculosis
      (24.5%), artery malformation (14.3%), lung carcinoma (9.5%) and idiopathic
      hemoptysis (2.0%). In many patients of tuberculosis and artery malformation,
      abnormal bronchial and nonbronchial systemic artery-pulmonary circulation shunts
      were usually found. During a mean follow-up period of 18 months (range from 1 day
      to 63 months), hemoptysis was controlled in 117(79.6%), ineffective and recurred
      in 30 (20.4%) and 14 (9.5%) required repeat embolization. A better success rate
      of 90.4% was obtained in the bronchiectasis group. The worse results were seen in
      the lung carcinoma group with 42.9%. The tuberculosis and artery malformation
      groups also demonstrated good results. Transient quadriplegia of major
      complication was recorded in 1/147 (0.7%). Minor complications such as chest
      pain, dysphagia and fever were recorded in 45/147 (30.6%). CONCLUSIONS: BAE and
      NBAE are safe and effective procedure for treatment for massive hemoptysis, with
      low recurrence and complication rates. Abnormal bronchial and nonbronchial
      systemic artery-pulmonary circulation shunts were usually found in many patients
      of tuberculosis and artery malformation. The better success rate was obtained by
      the bronchiectasis group, and ineffectiveness and high recurrence rate is
      associated with lung carcinoma.

PMID- 26221977
TI  - Endovascular revascularization is associated with a lower risk of above knee
      amputation than surgical or combined modalities. Analysis of English hospital
      admissions over a six year period.
AB  - BACKGROUND: We aimed to determine whether revascularization modality affected
      risk of an above knee amputation (AKA) in patients with peripheral arterial
      disease. METHODS: We used English hospital data and began by determining the
      number of major amputations and revascularization procedures performed between
      1st April 2003- 31st March 2009. We then extracted demographic (age, sex, level
      of deprivation, treatment location), comorbidity (diabetes, hypertension,
      hypercholesterolemia, coronary heart disease, ischemic cerebrovascular disease
      and smoking) and revascularization modality (endovascular/surgical) data. Multi
      variate analysis determined the odds ratios of an AKA in relation to previous
      revascularization attempts (if any). RESULTS: Over the six year period, there
      were 25,312 major amputations of which 7544 (29.4%) were linked to a
      revascularization attempt. Level of amputation was significantly influenced by
      previous revascularization. Compared to patients not linked to revascularization,
      those requiring endovascular treatment were less likely to undergo an AKA (OR
      0.82; 95% CI 0.75-0.90). Surgical (OR 1.16; 1.07-1.25) and combined
      endovascular/surgical treatment (OR 1.24; 1.09-1.40) had the opposite effect. Men
      (0.64; 0.55-0.74) and diabetics (0.44; 0.55-0.74) were less likely to undergo an
      AKA whereas patients with coronary (1.28; 1.10-1.47) or cerebrovascular (1.90;
      1.33-2.71) disease were more likely to have the procedure. Age, deprivation,
      hypertension, hypercholesterolemia, smoking and geographical location did not
      influence the level of amputation. CONCLUSIONS: When a major leg amputation is
      necessary, the risk of this being carried out above the knee may be lowest after
      endovascular revascularization attempts and highest after combined endovascular
      and surgical treatment.

PMID- 26221978
TI  - Aortic diseases and obstructive sleep apnea.
AB  - INTRODUCTION: Obstructive sleep apnea (OSA), particularly moderate-to-severe OSA,
      increases all-cause mortality as well as cardiovascular events, and continuous
      positive airway pressure (CPAP) therapy can reduce cardiovascular events and
      mortality. In 2003, it was first shown that patients with thoracic aortic
      dissection (AD) presented a high prevalence of previously undiagnosed and
      frequently severe OSA. Since then, a number of authors have investigated the
      association of aortic diseases (including thoracic and abdominal aortic aneurysm
      as well as AD) with OSA. EVIDENCE ACQUISITION: In the present article, we
      reviewed, with a systematic literature search through May 2015, currently
      available clinical studies investigating the association of aortic diseases with
      OSA. EVIDENCE SYNTHESIS: It is suggested that OSA is highly prevalent in patients
      with aortic diseases and associated with aortic expansion. Through the nocturnal
      perturbations of intermittent hypoxia, intrathoracic pressure swings, and
      increased sympathetic neural activation, OSA patients appear to be at increased
      risk for vascular changes related to oxidative stress, inflammation, and
      endothelial dysfunction, which may present as risks for aortic diseases. Despite
      currently available findings, it remains unclear whether common etiology leads to
      both OSA and aortic diseases or whether OSA itself causes aortic diseases.
      CONCLUSIONS: The following types of studies with long-term follow-up would be
      required: 1) a prospective cohort study comparing the incidence of aortic
      diseases in OSA patients with that in non-OSA subjects and 2) a randomized
      controlled trial determining whether CPAP therapy for OSA reduces the incidence
      of aortic diseases.

PMID- 26221979
TI  - Fibronectin mediates enhanced wear protection of lubricin during shear.
AB  - Fibronectin (FN) is a glycoprotein found in the superficial zone of cartilage;
      however, its role in the lubrication and the wear protection of articular joints
      is unknown. In this work, we have investigated the molecular interactions between
      FN and various components of the synovial fluid such as lubricin (LUB),
      hyaluronan (HA), and serum albumin (SA), which are all believed to contribute to
      joint lubrication. Using a Surface Forces Apparatus, we have measured the normal
      (adhesion/repulsion) and lateral (friction) forces across layers of individual
      synovial fluid components physisorbed onto FN-coated mica substrates. Our chief
      findings are (i) FN strongly tethers LUB and HA to mica, as indicated by high and
      reversible long-range repulsive normal interactions between surfaces, and (ii) FN
      and LUB synergistically enhance wear protection of surfaces during shear, as
      suggested by the structural robustness of FN+LUB layers under pressures up to
      about 4 MPa. These findings provide new insights into the role of FN in the
      lubricating properties of synovial fluid components sheared between ideal
      substrates and represent a significant step forward in our understanding of
      cartilage damage involved in diseases such as osteoarthritis. 

PMID- 26221980
TI  - Cotton polyamine oxidase is required for spermine and camalexin signalling in the
      defence response to Verticillium dahliae.
AB  - Verticillium dahliae is a destructive, soil-borne fungal pathogen that causes
      vascular wilt disease in many economically important crops worldwide. A polyamine
      oxidase (PAO) gene was identified and cloned by screening suppression subtractive
      hybridisation and cDNA libraries of cotton genotypes tolerant to Verticillium
      wilt and was induced early and strongly by inoculation with V. dahliae and
      application of plant hormone. Recombinant cotton polyamine oxidase (GhPAO) was
      found to catalyse the conversion of spermine (Spm) to spermidine (Spd) in vitro.
      Constitutive expression of GhPAO in Arabidopsis thaliana produced improved
      resistance to V. dahliae and maintained putrescine, Spd and Spm at high levels.
      Hydrogen peroxide (H2 O2 ), salicylic acid and camalexin (a phytoalexin) levels
      were distinctly increased in GhPAO-overexpressing Arabidopsis plants during V.
      dahliae infection when compared with wild-type plants, and Spm and camalexin
      efficiently inhibited growth of V. dahliae in vitro. Spermine promoted the
      accumulation of camalexin by inducing the expression of mitogen-activated protein
      kinases and cytochrome P450 proteins in Arabidopsis and cotton plants. The three
      polyamines all showed higher accumulation in tolerant cotton cultivars than in
      susceptible cotton cultivars after inoculation with V. dahliae. GhPAO silencing
      in cotton significantly reduced the Spd level and increased the Spm level,
      leading to enhanced susceptibility to infection by V. dahliae, and the levels of
      H2 O2 and camalexin were distinctly lower in GhPAO-silenced cotton plants after
      V. dahliae infection. Together, these results suggest that GhPAO contributes to
      resistance of the plant against V. dahliae through the mediation of Spm and
      camalexin signalling. 

PMID- 26221981
TI  - Inelastic x-ray scattering in heterostructures: electronic excitations in
      LaAlO3/SrTiO3.
AB  - We present an investigation of the valence-electron excitation spectra including
      the collective plasmon modes of SrTiO3, LaAlO3 and their heterostructures with
      non-resonant inelastic x-ray scattering. We analyse the spectra using
      calculations based on first principles and atomic multiplet models. We
      demonstrate the feasibility of performing valence IXS experiments in a total
      reflection geometry. Surprisingly, we find that the plasmon, interband and
      semicore excitations in multilayers are well described as a superposition of bulk
      compound spectra even in a superstructure composing of layers of only one atomic
      layer thickness. 

PMID- 26221982
TI  - Paleolimnological inferences based on Oligocene ostracods (Crustacea: Ostracoda)
      from Tremembe Formation, Southeast Brazil.
AB  - Non-marine Oligocene ostracods from Tremembe Formation (Taubate Basin, Southeast
      Brazil) are studied for the first time. The study reveals rich assemblages which
      are probably composed of many new taxa, two of which are described here. The
      sixteen ostracod species registered are classified in the generaCypretta Vavra,
      Strandesia Stuhlmann,Potamocypris Brady, Heterocypris Claus,Eucypris Vavra,
      Herpetocypris Brady and Norman, Cytheridella Daday and LimnocythereBrady. Two new
      species of the latter are herein proposed: L. mandubi sp. nov. and L. katu sp.
      nov. The succession of ostracod assemblages along the studied core changes
      conspicuously in composition, abundance and preservation, and are characterized
      by the following associations: Herpetocypris-Cytheridella (lower), Limnocythere
      Cypretta (middle) andPotamocypris-Heterocypris (upper). It is assumed that these
      associations represent different ecological phases of the paleolake Taubate which
      is in accordance to previous stratigraphic and paleontological studies in the
      basin. The results from this pioneering taxonomic and paleoecological study on
      ostracods from Tremembe Formation reinforce the potential of these fossils for
      paleolimnological researches in Brazilian Cenozoic deposits.

PMID- 26221983
TI  - A comparative study of nutritional composition and potential use of some
      underutilized tropical fruits of Arecaceae.
AB  - In this study, pulp and kernel of fruits from six Arecaceae species were
      subjected to proximate analysis, fatty acid composition and total carotenoid
      content analysis. The species with the highest carbohydrate, lipid and protein
      values were Ptychosperma macarthurii(70.1 g/100 g in the kernel), Syagrus
      cearensis(40.6 g/100 g in the kernel), andS. coronata(20.6 g/100 g in the pulp).
      The ash content ranged from 0.61 to 7.51 g/100 g. Lauric, palmitic, and oleic
      acids were the major fatty acids identified. The total carotenoid contents and
      retinol activity equivalents were highest in the Pinanga kuhlii (180.3 ug/g) and
      Acrocomia intumescens (138.0 ug/g) pulp oils. Retinol activity equivalents varied
      between the investigated species (456 to 1515 MUg RAE/100 g). Native species such
      as A. intumescens, S. coronata, and S. cearensis are good sources of fresh food
      for the underserved populations that inhabit poorly developed areas such as the
      semi-arid region of Brazil. P. macarthurii, an exotic species, is an excellent
      source of ash and carotenoids, demonstrating its potential both as a food source
      and as bioactive compounds. Pulp and kernel ofA. intumescens,could be a good
      alternative feedstock for soap and biodiesel production, respectively.

PMID- 26221984
TI  - Anesthetic activity and bio-guided fractionation of the essential oil of Aloysia
      gratissima (Gillies & Hook.) Tronc. in silver catfish Rhamdia quelen.
AB  - This work aimed to determine the efficacy of the essential oil of A. gratissima
      as anesthetic for silver catfish, and to perform the bio-guided fractionation of
      essential oil aiming to isolate compounds responsible for the noted effects. Fish
      were submitted to anesthesia bath with essential oil, its fractions and isolated
      compounds to determine time of anesthetic induction and recovery. Eugenol (50 mg
      L(-1)) was used as positive control. Essential oil of A. gratissima was effective
      as an anesthetic at concentrations of 300 to 900 mg L(-1). Fish presented
      involuntary muscle contractions during induction and recovery. The bio-guided
      fractionation of essential oil furnished E-(-)-pinocamphone, (-)-caryophyllene
      oxide, (-)-guaiol and (+)-spathulenol. E-(-)-pinocamphone caused the same side
      effects observed for essential oil. (-)-Caryophyllene oxide, (-)-guaiol and (+)
      spathulenol showed only sedative effects at proportional concentrations to those
      of the constituents in essential oil. (+)-Spathulenol (51.2 mg L(-1)) promoted
      deep anesthesia without side effects. A higher concentration of (+)-spathulenol,
      and lower or absent amounts ofE-(-)-pinocamphone could contribute to increase the
      activity and safety of the essential oil of A. gratissima. (+)-Spathulenol showed
      potent sedative and anesthetic activities in silver catfish, and could be
      considered as a viable compound for the development of a new anesthetic.

PMID- 26221985
TI  - Effects of hormonal priming on seed germination of pigeon pea under cadmium
      stress.
AB  - In this work we investigated whether priming with auxin, cytokinin, gibberellin,
      abscisic acid and ethylene, alters the physiological responses of seeds of pigeon
      pea germinated under water and cadmium stress. Seeds treated with water or non
      treated seeds were used as control. Although compared to non-treated seeds we
      found that the hormone treatments improve the germination of pigeon pea under
      cadmium stress, however, these treatments did not differ from water. However, we
      also observed a trend of tolerance to the effects of cadmium in the presence of
      ethylene, suggesting that the use of this hormone may be an efficient method to
      overcome seed germination under metal stress. 

PMID- 26221986
TI  - Anthranilic acids from isatin: an efficient, versatile and environmentally
      friendly method.
AB  - This paper describes the preparation of a series of 16 anthranilic acids in
      yields ranging from 51 to 97%, by treating the isatins with NaOH and H2O2.
      Independently of the nature of the substituent on the aromatic ring, the
      reactions were complete in 15 min at room temperature, whereas those of isatins
      containing a substituent on the nitrogen atom required longer reaction time for
      completion (45 min) under the same reaction conditions. 

PMID- 26221987
TI  - Monitoring studies should consider temporal variability to reveal relations
      between cyanobacterial abundance and environmental variables.
AB  - One of the main goals of monitoring cyanobacteria blooms in aquatic environments
      is to reveal the relationship between cyanobacterial abundance and environmental
      variables. Studies typically correlate data that were simultaneously sampled.
      However, samplings occur sparsely over time and may not reveal the short-term
      responses of cyanobacterial abundance to environmental changes. In this study, we
      tested the hypothesis that stronger cyanobacteria x environment relationships in
      monitoring are found when the temporal variability of sampling points is
      incorporated in the statistical analyses. To this end, we investigated
      relationships between cyanobacteria and seven environmental variables that were
      sampled twice yearly for three years across 11 reservoirs, and data from an
      intensive monitoring in one of these reservoirs. Poor correlations were obtained
      when correlating data simultaneously sampled. In fact, the 'highly recurrent'
      role of phosphorus in cyanobacteria blooms is not properly observed in all
      sampling periods. On the other hand, the strongest correlation values for the
      total phosphorus x cyanobacteria relationship were observed when we used the
      variation of sampling points. We have also shown that environment variables
      better explain cyanobacteria when a time lag is considered. We conclude that, in
      cyanobacteria monitoring, the best approach to reveal determinants of
      cyanobacteria blooms is to consider environmental variability. 

PMID- 26221988
TI  - A science framework (SF) for agricultural sustainability.
AB  - The significance of Science Framework (SF) to date is receiving more acceptances
      all over the world to address agricultural sustainability. The professional
      views, however, advocate that the SF known as Mega Science Framework (MSF) in the
      transitional economies is not converging effectively in many ways for the
      agricultural sustainability. Specially, MSF in transitional economies is mostly
      incapable to identify barriers in agricultural research, inadequate to frame
      policy gaps with the goal of strategizing the desired sustainability in
      agricultural technology and innovation, inconsistent in finding to identify the
      inequities, and incompleteness to rebuild decisions. Therefore, this study
      critically evaluates the components of MSF in transitional economies and
      appraises the significance, dispute and illegitimate issue to achieve successful
      sustainable development. A sound and an effective MSF can be developed when there
      is an inter-linkage within principal components such as of (a) national
      priorities, (b) specific research on agricultural sustainability, (c) adequate
      agricultural research and innovation, and (d) alternative policy alteration. This
      maiden piece of research which is first its kind has been conducted in order to
      outline the policy direction to have an effective science framework for
      agricultural sustainability. 

PMID- 26221989
TI  - Reproductive morphology of female Guiana dolphins (Sotalia guianensis).
AB  - The reproductive morphology of cetaceans is poorly studied and, despite the large
      number of strandings, reports on this subject are scarce due to access to
      carcasses mostly in an advanced state of decomposition. The present study aimed
      to describe histological characteristics of the female genital tract of Sotalia
      guianensis, in order to assist in future studies on the reproductive biology of
      these animals. Females of different ages, from stranding events on beaches in
      northeastern Brazil, were used. Fragments of all organs were collected and
      processed for light and scanning electron microscopy. Histological analyses
      showed that these structures were similar to those found in terrestrial mammals,
      with some peculiarities, such as the presence of differentiated cells in the
      vulvar subepidermal layer, not described in the literature on cetaceans.
      Reproductive studies with a morphological description of the female genital
      organs are extremely important, since they would enable a better understanding of
      the species reproductive physiology and assist in the development of new
      strategies for the species conservation.

PMID- 26221990
TI  - Estimating of gross primary production in an Amazon-Cerrado transitional forest
      using MODIS and Landsat imagery.
AB  - The acceleration of the anthropogenic activity has increased the atmospheric
      carbon concentration, which causes changes in regional climate. The Gross Primary
      Production (GPP) is an important variable in the global carbon cycle studies,
      since it defines the atmospheric carbon extraction rate from terrestrial
      ecosystems. The objective of this study was to estimate the GPP of the Amazon
      Cerrado Transitional Forest by the Vegetation Photosynthesis Model (VPM) using
      local meteorological data and remote sensing data from MODIS and Landsat 5 TM
      reflectance from 2005 to 2008. The GPP was estimated using Normalized Difference
      Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) calculated by MODIS
      and Landsat 5 TM images. The GPP estimates were compared with measurements in a
      flux tower by eddy covariance. The GPP measured in the tower was consistent with
      higher values during the wet season and there was a trend to increase from 2005
      to 2008. The GPP estimated by VPM showed the same increasing trend observed in
      measured GPP and had high correlation and Willmott's coefficient and low error
      metrics in comparison to measured GPP. These results indicated high potential of
      the Landsat 5 TM images to estimate the GPP of Amazon-Cerrado Transitional Forest
      by VPM. 

PMID- 26221991
TI  - The length of the dry season may be associated with leaf scleromorphism in
      cerrado plants.
AB  - Despite limitations of low fertility and high acidity of the soils, the cerrado
      flora is the richest amongst savannas. Many cerrado woody species show
      sclerophyllous leaves, which might be related to the availability of water and
      nutrients in the soil. To better understand the function and structure of cerrado
      vegetation within its own variations, we compared two cerrado communities: one in
      its core region in central Brazil (Brasilia, DF) and the other on its southern
      periphery (Itirapina, SP). We contrasted the length of the dry season, soil
      fertility rates, leaf concentrations of N, P, K, Ca and Mg and the specific leaf
      area (SLA) between these communities. The dry season was shorter on the
      periphery, where the soil was more fertile although more acidic. Plants from the
      periphery showed higher SLA and higher leaf concentrations of N, P, Ca and Mg. We
      propose that the higher SLA of plants from the periphery is related to the
      shorter dry season, which allows better conditions for nutrient uptake. 

PMID- 26221992
TI  - Initial development of the endocarp in Lithraea brasiliensis Marchand
      (Anacardiaceae): with taxonomic notes.
AB  - Investigation into the initial developmental stages of a given structure is
      fundamental for precise characterization as well as for comparative analysis in
      relation to other taxa when homologies are established. For the Anacardiaceae
      family, investigations of the initial development of the pericarp or its basic
      histological sites, the epicarp, mesocarp and endocarp, are relevant since these
      regions are of taxonomic and phylogenetic importance. The initial stages of
      endocarp development in Lithraea brasiliensis were studied using light
      microscopy. In L. brasiliensis, the fruits are of the drupe type. The endocarp
      originates exclusively in the epidermis of the locular cavity and is composed of
      only three strata. The crystalliferous layer, typical in fruits of the
      Anacardiaceae family, originates in the carpelar mesophyll and runs adjacent to
      the outermost layer of the endocarp. The endocarp in Lithraea brasiliensis is of
      the Anacardium type. The results of the present study are important for the
      identification of the Lithraea species that occur in the state of Rio Grande do
      Sul. In L. molleoides, the crystalliferous layer was shown to originate from the
      locular epidermis and this developmental aspect enables it to be differentiated
      from L. brasiliensis and demonstrates that there is variability of endocarp
      development in Lithraea.

PMID- 26221993
TI  - Interventions for preventing recurrent urinary tract infection during pregnancy.
AB  - BACKGROUND: Recurrent urinary tract infections (RUTI) are common in women who are
      pregnant and may cause serious adverse pregnancy outcomes for both mother and
      child including preterm birth and small-for-gestational-age babies. Interventions
      used to prevent RUTI in women who are pregnant can be pharmacological
      (antibiotics) or non-pharmacological (cranberry products, acupuncture, probiotics
      and behavioural modifications). So far little is known about the best way to
      prevent RUTI in pregnant women. OBJECTIVES: To assess the effects of
      interventions for preventing RUTI in pregnant women.The primary maternal outcomes
      were RUTI before birth (variously defined) and preterm birth (before 37 weeks).
      The primary infant outcomes were small-for-gestational age and total mortality.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (20 May 2015) and reference lists of retrieved articles. SELECTION
      CRITERIA: Published, unpublished and ongoing randomised controlled trials (RCTs),
      quasi-RCTs, clustered-randomised trials and abstracts of any intervention
      (pharmacological and non-pharmacological) for preventing RUTI during pregnancy
      (compared with another intervention, placebo or with usual care). DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed trials for inclusion and
      risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: The
      review included one trial involving 200 women and was at moderate to high risk of
      bias.The trial compared a daily dose of nitrofurantoin and close surveillance
      (regular clinic visit, urine cultures and antibiotics when a positive culture was
      found) with close surveillance only. No significant differences were found for
      the primary outcomes: recurrent pyelonephritis (risk ratio (RR) 0.89, 95%
      confidence interval (CI) 0.31 to 2.53; one study, 167 women), RUTI before birth
      (RR 0.30, 95% CI 0.06 to 1.38; one study, 167 women), and preterm birth (before
      37 weeks) (RR 1.18, 95% CI 0.42 to 3.35; one study, 147 women). The overall
      quality of evidence for these outcomes as assessed using GRADE was very low.
      There were no significant differences between the two comparison groups for any
      of the following secondary outcomes, birthweight less than 2500 (g) (RR 2.03, 95%
      CI 0.53 to 7.80; one study, 147 infants), birthweight (mean difference (MD) 
      113.00, 95% CI -327.20 to 101.20; one study, 147 infants), five-minute Apgar
      score less than seven (RR 2.03, 95% CI 0.19 to 21.87; one study, 147 infants) and
      miscarriages (RR 3.11, 95% CI 0.33 to 29.29; one study, 167 women). The evidence
      for these secondary outcomes was also of very low quality. The incidence of
      asymptomatic bacteriuria (ASB) (at least 10(3) colonies per mL) (secondary
      outcome), only reported in women with a clinic attendance rate of more than 90%
      (RR 0.55, 95% CI 0.34 to 0.89; one study, 102 women), was significantly reduced
      in women who received nitrofurantoin and close surveillance. Data on total
      mortality and small-for-gestational-age babies were not reported. AUTHORS'
      CONCLUSIONS: A daily dose of nitrofurantoin and close surveillance has not been
      shown to prevent RUTI compared with close surveillance alone. A significant
      reduction of ASB was found in women with a high clinic attendance rate and who
      received nitrofurantoin and close surveillance. There was limited reporting of
      both primary and secondary outcomes for both women and infants. No conclusions
      can be drawn regarding the optimal intervention to prevent RUTI in women who are
      pregnant. Randomised controlled trials comparing different pharmacological and
      non-pharmacological interventions are necessary to investigate potentially
      effective interventions to prevent RUTI in women who are pregnant.

PMID- 26221994
TI  - Histologic Grade and Mitotic Index as Predictors of Microvascular Invasion in
      Hepatocellular Carcinoma.
AB  - OBJECTIVES: Microvascular invasion is a well-known risk factor for hepatocellular
      carcinoma recurrence and mortality after hepatic resection and liver transplant.
      We sought to determine the clinico-pathological predictive factors associated
      with microvascular invasion. MATERIALS AND METHODS: We studied all patients who
      had undergone liver transplant because of hepatocellular carcinoma between July
      2001 and December 2010 at our institution. Laboratory tests, clinical, and
      demographic data were obtained. Histopathological hematoxylin and eosin specimens
      were performed by a single liver pathologist. RESULTS: During the study, 107
      patients had LT because of HCC and they were selected for this investigation: 76
      were men (71%) and 31 women (29%) (mean age, 56.8 +/- 8.7 y). It was not possible
      to retrieve histologic samples from 5 patients; therefore, the final studied
      analysis was 102 individuals. Tumor recurrence rate was 12.9%. One-, three- and
      five-year overall survivals were 75.0%, 71.4%, and 67.5%. Mitotic index,
      histologic grade, tumor architecture, alpha-fetoprotein, and tumor fibrosis were
      associated with microvascular invasion on univariate analysis. Significant
      independent predictors of microvascular invasion on logistic regression analysis
      were histologic grade and mitotic index (P < .001; odds ratio, 3.16; 95%
      confidence interval, 1.525-4.156, and P = .046; odds ratio, 2.56; 95% confidence
      interval, 1.061-6.451). CONCLUSIONS: Mitotic index and histologic grade are
      significant predictors of microvascular invasion. No other risk factor was
      identified in the logistic regression. As both pathological characteristics may
      be assessed by liver biopsy, these results highlight the importance of discussing
      pretransplant liver biopsy to access prognosis and define treatment modalities in
      the setting of liver transplant.

PMID- 26221995
TI  - Molecular and Morphological Evidence Demonstrating Two Species of Helicometrina
      Linton 1910 (Digenea: Opecoelidae) in Northern Chile.
AB  - The opecoelid Helicometrina nimia Linton, 1910 has been reported from numerous
      marine fishes along the Pacific and Atlantic coasts of the Americas. Along the
      Chilean coast, H. nimia is found in fishes belonging to at least 9 families. This
      surprisingly low host specificity of H. nimia raises question about the correct
      identification of specimens assigned to this species. Here we evaluate whether H.
      nimia specimens isolated from sympatric fish species in northern Chile but with
      different diets and found in different habitats (water column and demersal) are
      the same species. Our results demonstrate that specimens from the shallow benthic
      fish Labrisomus philippii (Steindachner) do not correspond to H. nimia but
      instead belong to a new species of Helicometrina. This species is described and
      distinguished from H. nimia using morphological descriptions and 2 molecular
      markers (the cytochrome c oxidase subunit 1 gene and the V4 region of the SSU
      rRNA gene). The new species Helicometrina labrisomi (Digenea: Opecoelidae), is
      found in the intestine of L. philippii (Steindachner, 1866) (Pisces:
      Labrisomidae), a shallow benthic fish that inhabits the northern coast of Chile.
      We also studied the related Helicometrina nimia Linton, 1910 from the
      benthopelagic fishes Paralabrax humeralis (Valenciennes, 1828) and Acanthistius
      pictus (Tschudi, 1846) (Serranidae). The new species differs from H. nimia by a
      combination of characters that include ovary shape, number of uterine loops, and
      position of the genital pore. Our results indicate that morphological
      characteristics, such as body size, extent of the vitellarium, shape of the
      testes, and cirrus sac size and extent, traditionally used in the taxonomy of
      Helicometrina are highly variable. In contrast, meristic and morphological
      characteristics, such as a lobed ovary, the number of uterine loops, dimensions
      of the pharynx, and the opening of the genital pore, are highly constant. 

PMID- 26221996
TI  - A new potent immunosuppressive isoflavanonol from Campylotropis hirtella.
AB  - Four new flavonoids were isolated from Campylotropis hirtella and these are a
      chromone and a 2H-chromene, an isoflavone and an isoflavanonol. The structures of
      these compounds were elucidated by extensive spectroscopic measurements. All of
      the compounds were assessed for immunosuppressive activity. Compound 4 showed
      very strong T lymphocyte suppression activity (IC50: 0.13 MUM) and potent B
      lymphocyte suppression activity (IC50: 0.26 MUM). Due to its potent
      immunosuppressive activity and lower cytotoxicity, further structure-activity
      studies will be pursued on this compound. 

PMID- 26221997
TI  - The History of Biological Weapons Use: What We Know and What We Don't.
AB  - This article critically reviews the literature on the history of biological
      warfare, bioterrorism, and biocrimes. The first serious effort to review this
      entire history, made in 1969, had numerous limitations. In recent decades,
      several authors have filled many of the gaps in our understanding of the past use
      of biological agents (including both pathogens and toxins), making it possible to
      reconstruct that history with greater fidelity than previously possible.
      Nevertheless, there are numerous remaining gaps, and closer inspection indicates
      that some supposed uses of biological weapons never took place or are poorly
      substantiated. Topics requiring additional research are identified. 

PMID- 26221998
TI  - Study of the anti-angiogenic effects of cardiolipin by the aortic ring assay.
AB  - Cardiolipin (CL), a phospholipid found in the inner mitochondrial membrane in all
      cell types, is critical for the function of the electron transport chain. The
      role of CL is not fully understood, but it is assumed that the molecule maintains
      membrane potential and architecture and compensates for alterations in
      homeostasis that could affect the energy metabolism. The objective of this
      project was to determine the effects of increasing CL concentrations on
      angiogenic sprouting by using the aortic ring assay model. For this, 5-day-old
      C57Bl/6 pups were euthanized by cervical dislocation prior to removal of the
      aortas. The vessels were cleaned, cut in 0.5 mm wide rings, and placed in a
      collagen growth matrix supplemented with CL. The results revealed a highly
      significant reduction of sprout growth (both length and quantity) at low,
      physiological concentrations. In conclusion, the results of this study
      demonstrate that CL significantly reduces microvessel formation and that it could
      potentially provide an interesting novel therapeutic target for angiogenesis. 

PMID- 26221999
TI  - Nigella sativa oil attenuates chronic nephrotoxicity induced by oral sodium
      nitrite: Effects on tissue fibrosis and apoptosis.
AB  - OBJECTIVES: Sodium nitrite, a food preservative, has been reported to increase
      oxidative stress indicators such as lipid peroxidation, which can affect
      different organs including the kidney. Here, we investigated the toxic effects of
      oral sodium nitrite on kidney function in rats and evaluated potential protective
      effects of Nigella sativa oil (NSO). METHODS: Seventy adult male Sprague-Dawley
      rats received 80 mg/kg sodium nitrite orally in the presence or absence of NSO
      (2.5, 5, and 10 ml/kg) for 12 weeks. Morphological changes were assessed by
      hematoxylin and eosin, Mallory trichome, and periodic acid-Schiff staining. Renal
      tissues were used for measurements of oxidative stress markers, C-reactive
      protein, cytochrome C oxidase, transforming growth factor (TGF)-beta1, monocyte
      chemotactic protein (MCP)-1, pJNK/JNK, and caspase-3. RESULTS: NSO significantly
      reduced sodium nitrite-induced elevation in serum urea and creatinine, as well as
      increasing normal appearance of renal tissue. NSO also prevented reductions in
      glycogen levels caused by sodium nitrite alone. Moreover, NSO treatment resulted
      in dose-dependent significant reductions in fibrosis markers after sodium nitrite
      induced 3- and 2.7-fold increase in MCP-1 and TGF-beta1, respectively. Finally,
      NSO partially reduced the elevated caspase-3 and pJNK/JNK. DISCUSSION: NSO
      ameliorates sodium nitrite-induced nephrotoxicity through blocking oxidative
      stress, attenuation of fibrosis/inflammation, restoration of glycogen level,
      amelioration of cytochrome C oxidase, and inhibition of apoptosis.

PMID- 26222001
TI  - The relation between ACE D/I and CYP11B2 C-344T  polymorphisms and parameters of
      arterial stiffness in  the context of renal sodium handling.
AB  - BACKGROUND: Sodium overload is related to the development of primary hypertension
      and its complications. METHODS: In 131 (65 female) treated hypertensives (average
      blood pressure 144/82 mmHg and duration of hypertension 11.7 years), we measured
      peripheral and central arterial pressures, peripheral (AIx(P)) and central
      (AIx(C1), AIx(C2)) augmentation indices, pulse-wave velocity (PWV) and daily
      urinary sodium excretion, and conducted genetic studies of ACE D/I and CYP11B2 C
      344T polymorphisms. Proximal (FE(Li)) and distal (FDR(Na)) sodium reabsorption
      measurements were performed using endogenous lithium clearance. RESULTS: We found
      statistically significant interactions between FE(Li) and ACE D/I polymorphism
      with respect to AIx(C2) (P(INT) = 0.05) and between FE(Li) and CYP11B2 C-344T
      polymorphism with respect to AIx(C1) (P(INT) = 0.01), AIx(C2) (P(INT) = 0.04) and
      AIx(P) (P(INT) = 0.01). In the group of ACE I allele carriers compared with DD
      homozygotes, the AIx(C1) (154.1 vs 140.6%; p = 0.02), AIx(C2) (33.3 vs 26.9%; p =
      0.02) and AIx(P) (94.6 vs 85.2%; p = 0.01) were higher in the subgroup with
      FE(Li) below the median value (FE(Li)1), but not in the subgroup with FE(Li)
      above the median value (FE(Li)2). In the group of CYP11B2 TT homozygotes compared
      with C allele carriers, we observed higher values of AIx(C1) (158.5 vs 146.4%; p
      = 0.03), AIx(C2) (36.0 vs 29.4%; p = 0.01) and AIx(P) (99.0 vs 88.7%; p = 0.005)
      in the FE(Li)1 but not the FE(Li)2 subgroup. Conclusions. In the population with
      assumed high dietary sodium intake and long-standing history of hypertension, the
      relation between proximal sodium reabsorption and the development of arterial
      stiffness depends on the genetic context of the selected genetic polymorphisms of
      the renin-angiotensin-aldosterone system, independent of blood pressure.

PMID- 26222010
TI  - Psychological and autonomic effects of art making in college-aged students.
AB  - BACKGROUND AND OBJECTIVES: Anxiety disorders comprise the most common category of
      mental illness among US young adults. Art making might be one method to help
      reduce anxiety, but the few studies investigating this have used only subjective
      measures of anxiety. DESIGN: This study employed both subjective (self-reported
      state anxiety from the State-Trait Anxiety Inventory) and objective (heart rate
      variability) measures to assess whether 30-minute periods of art making reduced
      anxiety in 47 first-year college students prior to their final examinations.
      METHODS: Students participated in free-form painting, mandala coloring, clay
      modeling, and control sessions. RESULTS: Repeated-measures ANOVA with post hoc
      analysis revealed significantly greater pre- to post-session reductions in
      anxiety for all three types of art-making sessions than for the control session,
      as measured objectively. Measured subjectively, only free-form painting yielded a
      significant decrease in anxiety compared to the control session. CONCLUSIONS:
      Given the health benefits of anxiety reduction, further study is warranted to
      determine the duration of art making's anxiety-reducing effect.

PMID- 26222011
TI  - Influence of an Allergen-Specific Th17 Response on Remodeling of the Airways.
AB  - We showed previously that sensitization of mice with dendritic cells (DCs) via
      the airways depends on activation of these cells with LPS. Allergen-pulsed DCs
      that were stimulated with low doses of LPS induce a strong Th2 response in vivo.
      Our objective was to investigate whether airway sensitization of mice by the
      application of DCs with a phenotype that is able to induce Th17 cells results in
      increased remodeling of the airways. We generated DCs from the bone marrow of
      mice and pulsed them with LPS-free ovalbumin. Subsequently, cells were activated
      with LPS with or without ATP for inflammasome activation. The activated cells
      were used to sensitize mice via the airways. Intranasal instillation of DCs that
      were activated with 0.1 ng/ml LPS induced a Th2 response with airway
      eosinophilia. High doses of LPS, particularly when given in combination with ATP,
      led to induction of a mixed Th2/Th17 response. Interestingly, we found a
      correlation between IL-17A production and the remodeling of the airways.
      Stimulation of mouse fibroblasts with purified IL-17A protein in vitro resulted
      in transforming growth factor-beta1 secretion and collagen transcription.
      Interestingly, we found enhanced secretion of transforming growth factor-beta1 by
      fibroblasts after costimulation with IL-17A and the profibrotic factor wingless
      type MMTV integration site family, member 5A (Wnt5a). We showed that an allergen
      specific Th17 response in the airway is accompanied by increased airway
      remodeling. Furthermore, we revealed that increased remodeling is not only based
      on neutrophilic inflammation, but also on the direct impact of IL-17A on airway
      structural cells. 

PMID- 26222013
TI  - Strong perpendicular exchange bias in epitaxial La(0.7)Sr(0.3)MnO3:BiFeO3
      nanocomposite films through vertical interfacial coupling.
AB  - An exchange bias effect with perpendicular anisotropy is of great interest owing
      to potential applications such as read heads in magnetic storage devices with
      high thermal stability and reduced dimensions. Here we report a novel approach
      for achieving perpendicular exchange bias by orienting the
      ferromagnetic/antiferromagnetic coupling in the vertical geometry through a
      unique vertically aligned nanocomposite (VAN) design. Our results demonstrate
      robust perpendicular exchange bias phenomena in micrometer-thick films employing
      a prototype material system of antiferromagnetic BiFeO3 and ferromagnetic
      La0.7Sr0.3MnO3. The unique response of exchange bias to a perpendicular magnetic
      field reveals the existence of exchange coupling along their vertical
      heterointerfaces, which exhibits a strong dependence on their strain states. This
      VAN approach enables a large selection of material systems for achieving
      perpendicular exchange bias, which could lead to advanced spintronic devices. 

PMID- 26222014
TI  - Mixed Matrix PVDF Membranes With in Situ Synthesized PAMAM Dendrimer-Like
      Particles: A New Class of Sorbents for Cu(II) Recovery from Aqueous Solutions by
      Ultrafiltration.
AB  - Advances in industrial ecology, desalination, and resource recovery have
      established that industrial wastewater, seawater, and brines are important and
      largely untapped sources of critical metals and elements. A Grand Challenge in
      metal recovery from industrial wastewater is to design and synthesize high
      capacity, recyclable and robust chelating ligands with tunable metal ion
      selectivity that can be efficiently processed into low-energy separation
      materials and modules. In our efforts to develop high capacity chelating
      membranes for metal recovery from impaired water, we report a one-pot method for
      the preparation of a new family of mixed matrix polyvinylidene fluoride (PVDF)
      membranes with in situ synthesized poly(amidoamine) [PAMAM] particles. The key
      feature of our new membrane preparation method is the in situ synthesis of PAMAM
      dendrimer-like particles in the dope solutions prior to membrane casting using
      low-generation dendrimers (G0 and G1-NH2) with terminal primary amine groups as
      precursors and epichlorohydrin (ECH) as cross-linker. By using a combined
      thermally induced phase separation (TIPS) and nonsolvent induced phase separation
      (NIPS) casting process, we successfully prepared a new family of asymmetric PVDF
      ultrafiltration membranes with (i) neutral and hydrophilic surface layers of
      average pore diameters of 22-45 nm, (ii) high loadings (~48 wt %) of dendrimer
      like PAMAM particles with average diameters of ~1.3-2.4 MUm, and (iii) matrices
      with sponge-like microstructures characteristics of membranes with strong
      mechanical integrity. Preliminary experiments show that these new mixed matrix
      PVDF membranes can serve as high capacity sorbents for Cu(II) recovery from
      aqueous solutions by ultrafiltration.

PMID- 26222015
TI  - Metal-Free Thiocyanation of Imidazoheterocycles through Visible Light Photoredox
      Catalysis.
AB  - A visible light mediated, metal-free process for the thiocyanation of
      imidazoheterocycles has been developed using eosin Y as a photoredox catalyst
      under ambient air at room temperature. A library of 3-(thiocyanato)imidazo[1,2
      a]pyridines with broad functionalities have been synthesized in high yields. This
      methodology is also applicable for the selenocyanation of imidazo[1,2-a]pyridine.

PMID- 26222012
TI  - Modulation of inflammation by autophagy: Consequences for human disease.
AB  - Autophagy and inflammation are 2 fundamental biological processes involved in
      both physiological and pathological conditions. Through its crucial role in
      maintaining cellular homeostasis, autophagy is involved in modulation of cell
      metabolism, cell survival, and host defense. Defective autophagy is associated
      with pathological conditions such as cancer, autoimmune disease,
      neurodegenerative disease, and senescence. Inflammation represents a crucial line
      of defense against microorganisms and other pathogens, and there is increasing
      evidence that autophagy has important effects on the induction and modulation of
      the inflammatory reaction; understanding the balance between these 2 processes
      may point to important possibilities for therapeutic targeting. This review
      focuses on the crosstalk between autophagy and inflammation as an emerging field
      with major implications for understanding the host defense on the one hand, and
      for the pathogenesis and treatment of immune-mediated diseases on the other hand.

PMID- 26222016
TI  - Characterization of the acidic species of a monoclonal antibody using weak cation
      exchange chromatography and LC-MS.
AB  - Charge variants, especially acidic charge variants, of recombinant monoclonal
      antibodies have been challenging to fully characterize despite the fact that
      several posttranslational modifications have already been identified. The acidic
      species of a recombinant monoclonal antibody were collected using weak cation
      exchange (WCX)-10 chromatography and characterized by LC-MS at multiple levels.
      In this study, methionine oxidation and asparagine deamidation are the only two
      modifications identified in the acidic species. Incubation of the collected main
      chromatographic peak with hydrogen peroxide generated acidic species, which
      confirmed that acidic species were enriched in oxidized antibody. Differences
      observed between the original acidic species and the oxidization-induced acidic
      species indicate that different mechanisms are involved in the formation of
      acidic species. Additionally, acidic species were generated by thermal stress of
      the collected main peak from the original sample. Thermal stress of the collected
      main peak in pH 9 buffer or ammonium bicarbonate generated chromatograms that are
      highly similar to those from the analysis of the original molecule. LC-MS
      analysis identified oxidation of the same methionine residue and deamidation of
      the same asparagine in the corresponding acidic fractions generated by thermal
      stress; however, relatively lower levels of methionine oxidation and higher
      levels of asparagine deamdiation were observed. The results support the use of
      stressed conditions to generate low abundance species for detailed
      characterization of recombinant monoclonal antibody charge variants, but with
      caution. 

PMID- 26222017
TI  - Gelled Lyotropic Liquid Crystals.
AB  - In our previous work we were able to prove that gelled bicontinuous
      microemulsions are a novel type of orthogonal self-assembled system. The study at
      hand aims at complementing our previous work by answering the question of whether
      gelled lyotropic liquid crystals are also orthogonal self-assembled systems. For
      this purpose we studied the same system, namely, water-n-decane/12
      hydroxyoctadecanoic acid (12-HOA)-n-decyl tetraoxyethylene glycol ether (C10E4).
      The phase boundaries of the nongelled and the gelled lyotropic liquid crystals
      were determined visually and with (2)H NMR spectroscopy. Oscillating shear
      measurements revealed that the absolute values of the storage and loss moduli of
      the gelled liquid crystalline (LC) phases do not differ very much from those of
      the binary organogel. While both the phase behavior and the rheological
      properties of the LC phases support the hypothesis that gelled lyotropic liquid
      crystals are orthogonal self-assembled systems, freeze-fracture electron
      microscopy (FFEM) seems to indicate an influence of the gel network on the
      structure of the Lalpha phase and vice versa. 

PMID- 26222018
TI  - Performance assessments of vertically aligned carbon nanotubes multi-electrode
      arrays using Cath.a-differentiated (CAD) cells.
AB  - In this work, Cath.a-differentiated (CAD) cells were used in place of primary
      neuronal cells to assess the performance of vertically aligned carbon nanotubes
      (VACNTs) multi-electrode arrays (MEA). To fabricate high-performance MEA, VACNTs
      were directly grown on graphene/Pt electrodes via plasma enhanced chemical
      deposition technique. Here, graphene served as an intermediate layer lowering
      contact resistance between VACNTs and Pt electrode. In order to lower the
      electrode impedance and to enhance the cell adhesion, VACNTs-MEAs were treated
      with UV-ozone for 20 min. Impedance of VACNTs electrode at 1 kHz frequency
      exhibits a reasonable value (110 kOmega) for extracellular signal recording, and
      the signal to noise ratio the is good enough to measure low signal amplitude
      (15.7). Spontaneous firing events from CAD cells were successfully measured with
      VACNTs MEAs that were also found to be surprisingly robust toward the biological
      interactions. 

PMID- 26222019
TI  - Measuring Bipolar Charge and Mass Distributions of Powder Aerosols by a Novel
      Tool (BOLAR).
AB  - The Bipolar Charge Analyzer (BOLAR) was evaluated for measuring bipolar
      electrostatic charge and mass distributions of powder aerosols generated from a
      dry powder inhaler. Mannitol powder (5, 10, and 20 mg) was dispersed using an
      Osmohaler inhaler into the BOLAR at air flow rates of 30 or 60 L/min. As the
      aerosol sample was drawn through the BOLAR, the air flow was divided into six
      equal fractions. Five of them entered individual detection tubes with a defined
      cutoff diameter in the range of 0.95 to 16.36 MUm (depending on the flow rate)
      and the remaining (i.e., the sixth) fraction passed through a reference chamber.
      The aerosols that entered the detection tubes were separated according to the
      particle charge polarity (positive, negative, or neutral) and charge was measured
      by separate electrometers. The deposited powder of a single actuation from the
      inhaler was chemically assayed using high performance liquid chromatography.
      Additionally, the aerosol measurements were conducted on a modified Classic
      Electrical Low Pressure Impactor (ELPI) for comparison of the net specific charge
      per size fraction. Spray-dried mannitol carried significantly different
      positively and negatively charged particles in each of the five defined particle
      size fractions. The charge-to-mass ratio (q/m) of positively charged particles
      ranged from +1.11 to +32.57 pC/MUg and negatively charged particles ranged from 
      1.39 to -9.25 pC/MUg, resulting in a net q/m of -3.08 to +13.34 pC/MUg. The net
      q/m values obtained on the modified ELPI ranged from -5.18 to +4.81 pC/MUg, which
      were comparable to the BOLAR measurements. This is the first full report to
      utilize the BOLAR to measure bipolar charge and mass distributions of a powder
      aerosol. Positively and negatively charged particles were observed within each
      size fraction, and their corresponding q/m profiles were successfully
      characterized. Despite some potential drawbacks, the BOLAR has provided a new
      platform for investigating bipolar charge in powder aerosols for inhalation. 

PMID- 26222020
TI  - Urban Chagas disease in children and women in primary care centres in Buenos
      Aires, Argentina.
AB  - The primary objective of this study was to estimate the prevalence of this
      disease in women of childbearing age and children treated at health centres in
      underserviced areas of the city of Buenos Aires. Demographic and Chagas disease
      status data were collected. Samples for Chagas disease serology were obtained on
      filter paper and the reactive results were confirmed with conventional samples. A
      total of 1,786 subjects were screened and 73 positive screening results were
      obtained: 17 were from children and 56 were from women. The Trypanosoma cruzi
      infection risk was greater in those individuals who had relatives with Chagas
      disease, who remember seeing kissing bugs, who were of Bolivian nationality or
      were born in the Argentine province of Santiago del Estero. The overall
      prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is
      currently predominantly urban. The observed prevalence requires health programme
      activities that are aimed at urban children and their mothers. Most children were
      infected congenitally, which reinforces the need for Chagas disease screening of
      all pregnant women and their babies in Argentina. The active search for new cases
      is important because the appropriate treatment in children has a high cure rate.

PMID- 26222021
TI  - Evaluation of four colourimetric susceptibility tests for the rapid detection of
      multidrug-resistant Mycobacterium tuberculosis isolates.
AB  - The purpose of this study is to evaluate four rapid colourimetric methods,
      including the resazurin microtitre assay (REMA), malachite green decolourisation
      assay (MGDA), microplate nitrate reductase assay (MNRA) and crystal violet
      decolourisation assay (CVDA), for the rapid detection of multidrug-resistant
      (MDR) tuberculosis. Fifty Mycobacterium tuberculosis isolates were used in this
      study. Eighteen isolates were MDR, two isolates were only resistant to isoniazid
      (INH) and the remaining isolates were susceptible to both INH and rifampicin
      (RIF). INH and RIF were tested in 0.25 ug/mL and 0.5 ug/mL, respectively. The
      agar proportion method was used as a reference method. MNRA and REMA were
      performed with some modifications. MGDA and CVDA were performed as defined in the
      literature. The agreements of the MNRA for INH and RIF were 96% and 94%,
      respectively, while the agreement of the other assays for INH and RIF were 98%.
      In this study, while the specificities of the REMA, MGDA and CVDA were 100%, the
      specificity of the MNRA was lower than the others (93.3% for INH and 90.9% for
      RIF). In addition, while the sensitivity of the MNRA was 100%, the sensitivities
      of the others were lower than that of the MNRA (from 94.1-95%). The results were
      reported on the seventh-10th day of the incubation. All methods are reliable,
      easy to perform, inexpensive and easy to evaluate and do not require special
      equipment.

PMID- 26222022
TI  - Activation and cytokine profile of monocyte derived dendritic cells in leprosy:
      in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of
      IL-12p70 in lepromatous leprosy.
AB  - Dendritic cells (DCs) play a pivotal role in the connection of innate and
      adaptive immunity of hosts to mycobacterial infection. Studies on the interaction
      of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients
      are rare. The present study demonstrated that the differentiation of MOs to DCs
      was similar in all forms of leprosy compared to normal healthy individuals. In
      vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable
      degrees of DC maturation as determined by the increased expression of HLA-DR,
      CD40, CD80 and CD86, but not CD83, in all studied groups. The production of
      different cytokines by the MO-DCs appeared similar in all of the studied groups
      under similar conditions. However, the production of interleukin (IL)-12p70 by MO
      DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M.
      leprae was lower than tuberculoid leprosy patients and healthy individuals, even
      after CD40 ligation with CD40 ligand-transfected cells. The present cumulative
      findings suggest that the MO-DCs of LL patients are generally a weak producer of
      IL-12p70 despite the moderate activating properties ofM. leprae. These results
      may explain the poor M. leprae-specific cell-mediated immunity in the LL type of
      leprosy.

PMID- 26222024
TI  - Microbiology: Cyanate fuels the nitrogen cycle.

PMID- 26222023
TI  - HipBA-promoter structures reveal the basis of heritable multidrug tolerance.
AB  - Multidrug tolerance is largely responsible for chronic infections and caused by a
      small population of dormant cells called persisters. Selection for survival in
      the presence of antibiotics produced the first genetic link to multidrug
      tolerance: a mutant in the Escherichia coli hipA locus. HipA encodes a serine
      protein kinase, the multidrug tolerance activity of which is neutralized by
      binding to the transcriptional regulator HipB and hipBA promoter. The
      physiological role of HipA in multidrug tolerance, however, has been unclear.
      Here we show that wild-type HipA contributes to persister formation and that high
      persister hipA mutants cause multidrug tolerance in urinary tract infections.
      Perplexingly, high-persister mutations map to the N-subdomain-1 of HipA far from
      its active site. Structures of higher-order HipA-HipB-promoter complexes reveal
      HipA forms dimers in these assemblies via N-subdomain-1 interactions that occlude
      their active sites. High-persistence mutations, therefore, diminish HipA-HipA
      dimerization, thereby unleashing HipA to effect multidrug tolerance. Thus, our
      studies reveal the mechanistic basis of heritable, clinically relevant antibiotic
      tolerance. 

PMID- 26222025
TI  - Graphene kirigami.
AB  - For centuries, practitioners of origami ('ori', fold; 'kami', paper) and kirigami
      ('kiru', cut) have fashioned sheets of paper into beautiful and complex three
      dimensional structures. Both techniques are scalable, and scientists and
      engineers are adapting them to different two-dimensional starting materials to
      create structures from the macro- to the microscale. Here we show that graphene
      is well suited for kirigami, allowing us to build robust microscale structures
      with tunable mechanical properties. The material parameter crucial for kirigami
      is the Foppl-von Karman number gamma: an indication of the ratio between in-plane
      stiffness and out-of-plane bending stiffness, with high numbers corresponding to
      membranes that more easily bend and crumple than they stretch and shear. To
      determine gamma, we measure the bending stiffness of graphene monolayers that are
      10-100 micrometres in size and obtain a value that is thousands of times higher
      than the predicted atomic-scale bending stiffness. Interferometric imaging
      attributes this finding to ripples in the membrane that stiffen the graphene
      sheets considerably, to the extent that gamma is comparable to that of a standard
      piece of paper. We may therefore apply ideas from kirigami to graphene sheets to
      build mechanical metamaterials such as stretchable electrodes, springs, and
      hinges. These results establish graphene kirigami as a simple yet powerful and
      customizable approach for fashioning one-atom-thick graphene sheets into
      resilient and movable parts with microscale dimensions. 

PMID- 26222026
TI  - RNA degradation paths in a 12-subunit nuclear exosome complex.
AB  - The eukaryotic exosome is a conserved RNA-degrading complex that functions in RNA
      surveillance, turnover and processing. How the same machinery can either
      completely degrade or precisely trim RNA substrates has long remained
      unexplained. Here we report the crystal structures of a yeast nuclear exosome
      containing the 9-subunit core, the 3'-5' RNases Rrp44 and Rrp6, and the obligate
      Rrp6-binding partner Rrp47 in complex with different RNAs. The combined
      structural and biochemical data of this 12-subunit complex reveal how a single
      stranded RNA can reach the Rrp44 or Rrp6 active sites directly or can bind Rrp6
      and be threaded via the central channel towards the distal RNase Rrp44. When a
      bulky RNA is stalled at the entrance of the channel, Rrp6-Rrp47 swings open. The
      results suggest how the same molecular machine can coordinate processive
      degradation and partial trimming in an RNA-dependent manner by a concerted
      swinging mechanism of the two RNase subunits. 

PMID- 26222027
TI  - Synthetic biology: Ribosomal ties that bind.

PMID- 26222028
TI  - Corrigendum: Eocene primates of South America and the African origins of New
      World monkeys.

PMID- 26222029
TI  - DNA replication: Strand separation unravelled.

PMID- 26222030
TI  - Structure of the eukaryotic MCM complex at 3.8 A.
AB  - DNA replication in eukaryotes is strictly regulated by several mechanisms. A
      central step in this replication is the assembly of the heterohexameric
      minichromosome maintenance (MCM2-7) helicase complex at replication origins
      during G1 phase as an inactive double hexamer. Here, using cryo-electron
      microscopy, we report a near-atomic structure of the MCM2-7 double hexamer
      purified from yeast G1 chromatin. Our structure shows that two single hexamers,
      arranged in a tilted and twisted fashion through interdigitated amino-terminal
      domain interactions, form a kinked central channel. Four constricted rings
      consisting of conserved interior beta-hairpins from the two single hexamers
      create a narrow passageway that tightly fits duplex DNA. This narrow passageway,
      reinforced by the offset of the two single hexamers at the double hexamer
      interface, is flanked by two pairs of gate-forming subunits, MCM2 and MCM5. These
      unusual features of the twisted and tilted single hexamers suggest a concerted
      mechanism for the melting of origin DNA that requires structural deformation of
      the intervening DNA. 

PMID- 26222031
TI  - Cyanate as an energy source for nitrifiers.
AB  - Ammonia- and nitrite-oxidizing microorganisms are collectively responsible for
      the aerobic oxidation of ammonia via nitrite to nitrate and have essential roles
      in the global biogeochemical nitrogen cycle. The physiology of nitrifiers has
      been intensively studied, and urea and ammonia are the only recognized energy
      sources that promote the aerobic growth of ammonia-oxidizing bacteria and
      archaea. Here we report the aerobic growth of a pure culture of the ammonia
      oxidizing thaumarchaeote Nitrososphaera gargensis using cyanate as the sole
      source of energy and reductant; to our knowledge, the first organism known to do
      so. Cyanate, a potentially important source of reduced nitrogen in aquatic and
      terrestrial ecosystems, is converted to ammonium and carbon dioxide in
      Nitrososphaera gargensis by a cyanase enzyme that is induced upon addition of
      this compound. Within the cyanase gene family, this cyanase is a member of a
      distinct clade also containing cyanases of nitrite-oxidizing bacteria of the
      genus Nitrospira. We demonstrate by co-culture experiments that these nitrite
      oxidizers supply cyanase-lacking ammonia oxidizers with ammonium from cyanate,
      which is fully nitrified by this microbial consortium through reciprocal feeding.
      By screening a comprehensive set of more than 3,000 publically available
      metagenomes from environmental samples, we reveal that cyanase-encoding genes
      clustering with the cyanases of these nitrifiers are widespread in the
      environment. Our results demonstrate an unexpected metabolic versatility of
      nitrifying microorganisms, and suggest a previously unrecognized importance of
      cyanate in cycling of nitrogen compounds in the environment. 

PMID- 26222032
TI  - Protein synthesis by ribosomes with tethered subunits.
AB  - The ribosome is a ribonucleoprotein machine responsible for protein synthesis. In
      all kingdoms of life it is composed of two subunits, each built on its own
      ribosomal RNA (rRNA) scaffold. The independent but coordinated functions of the
      subunits, including their ability to associate at initiation, rotate during
      elongation, and dissociate after protein release, are an established model of
      protein synthesis. Furthermore, the bipartite nature of the ribosome is presumed
      to be essential for biogenesis, since dedicated assembly factors keep immature
      ribosomal subunits apart and prevent them from translation initiation. Free
      exchange of the subunits limits the development of specialized orthogonal genetic
      systems that could be evolved for novel functions without interfering with native
      translation. Here we show that ribosomes with tethered and thus inseparable
      subunits (termed Ribo-T) are capable of successfully carrying out protein
      synthesis. By engineering a hybrid rRNA composed of both small and large subunit
      rRNA sequences, we produced a functional ribosome in which the subunits are
      covalently linked into a single entity by short RNA linkers. Notably, Ribo-T was
      not only functional in vitro, but was also able to support the growth of
      Escherichia coli cells even in the absence of wild-type ribosomes. We used Ribo-T
      to create the first fully orthogonal ribosome-messenger RNA system, and
      demonstrate its evolvability by selecting otherwise dominantly lethal rRNA
      mutations in the peptidyl transferase centre that facilitate the translation of a
      problematic protein sequence. Ribo-T can be used for exploring poorly understood
      functions of the ribosome, enabling orthogonal genetic systems, and engineering
      ribosomes with new functions. 

PMID- 26222034
TI  - Mixed poly(dopamine)/poly(L-lysine) (composite) coatings: from assembly to
      interaction with endothelial cells.
AB  - Engineered polymer films are of significant importance in the field of
      biomedicine. Poly(dopamine) (PDA) is becoming more and more a key player in this
      context. Herein, we deposited mixed films consisting of PDA and poly(L-lysine)
      (PLL) of different molecular weights. The coatings were characterized by quartz
      crystal microbalance with dissipation monitoring, atomic force microscopy, and X
      ray photoelectron spectroscopy. The protein adsorption to the mixed films was
      found to decrease with increasing amounts of PLL. PDA/PLL capsules were also
      successfully assembled. Higher PLL content in the membranes reduced their
      thickness while the zeta-potential increased. Further, endothelial cell adhesion
      and proliferation over 96 h were found to be independent of the type of coating.
      Using PDA/PLL in liposome-containing composite coatings showed that sequential
      deposition of the layers yielded higher liposome trapping compared to one-step
      adsorption except for negatively charged liposomes. Association/uptake of
      fluorescent cargo by adherent endothelial cells was found to be different for PDA
      and PDA/PLL films. Taken together, our findings illustrate the potential of
      PDA/PLL mixed films as coatings for biomedical applications.

PMID- 26222035
TI  - Bisphosphonate-functionalized hyaluronic acid showing selective affinity for
      osteoclasts as a potential treatment for osteoporosis.
AB  - Current treatments for osteoporosis involve the administration of high doses of
      bisphosphonates (BPs) over a number of years. However, the efficiency of the
      absorption of these drugs and specificity towards targeted osteoclastic cells is
      still suboptimal. In this study, we have exploited the natural affinity of high
      (H) and low (L) molecular-weight hyaluronic acid (HA) towards a cluster of
      differentiation 44 (CD44) receptors on osteoclasts to use it as a biodegradable
      targeting vehicle. We covalently bonded BP to functionalised HA (HA-BP) and found
      that HA-BP conjugates were highly specific to osteoclastic cells and reduced
      mature osteoclast numbers significantly more than free BP. To study the uptake of
      HA-BP, we fluorescently derivatised the polymer-drug with fluorescein B
      isothiocyanate (FITC) and found that L-HA-BP could seamlessly enter osteoclastic
      cells. Alternatively, we tested polyvinyl alcohol (PVA) as a synthetic polymer
      delivery vehicle using similar chemistry to link BP and found that osteoclast
      numbers did not reduce in the same way. These findings could pave the way for
      biodegradable polymers to be used as vehicles for targeted delivery of anti
      osteoporotic drugs. 

PMID- 26222033
TI  - Polyactives: controlled and sustained bioactive release via hydrolytic
      degradation.
AB  - Significant and promising advances have been made in the polymer field for
      controlled and sustained bioactive delivery. Traditionally, small molecule
      bioactives have been physically incorporated into biodegradable polymers;
      however, chemical incorporation allows for higher drug loading, more controlled
      release, and enhanced processability. Moreover, the advent of bioactive
      containing monomer polymerization and hydrolytic biodegradability allows for
      tunable bioactive loading without yielding a polymer residue. In this review, we
      highlight the chemical incorporation of different bioactive classes into novel
      biodegradable and biocompatible polymers. The polymer design, synthesis, and
      formulation are summarized in addition to the evaluation of bioactivity retention
      upon release via in vitro and in vivo studies. 

PMID- 26222036
TI  - Heparin molecularly imprinted surfaces for the attenuation of complement
      activation in blood.
AB  - Heparin-imprinted synthetic polymer surfaces with the ability to attenuate
      activation of both the complement and the coagulation system in whole blood were
      successfully produced. Imprinting was achieved using a template coated with
      heparin, a highly sulfated glycosaminoglycan known for its anticoagulant
      properties. The N,N'-diacryloylpiperazine-methacrylic acid copolymers were
      characterized using goniometry, AFM and XPS. The influence of the molecular
      imprinting process on morphology and template rebinding was demonstrated by
      radioligand binding assays. Surface hemocompatibility was evaluated using human
      whole blood without anticoagulants followed by measurement of complement
      activation markers C3a and sC5b-9 and platelet consumption as a surrogate
      coagulation activation marker. The observed low thrombogenicity of this copolymer
      combined with the attenuation of complement activation induced by the molecular
      imprint offer potential for the development of self-regulating surfaces with
      important potential clinical applications. We propose a mechanism for the
      observed phenomena based upon the recruitment of endogenous sulfated
      glycosaminoglycans with heparin-like activities. 

PMID- 26222037
TI  - Redox-responsive supramolecular amphiphiles constructed via host-guest
      interactions for photodynamic therapy.
AB  - A supramolecular photosensitizer delivery system has been established through the
      self-assembly of supramolecular amphiphiles constructed by the host-guest
      interaction between poly(ethylene glycol)-beta-cyclodextrin (PEG-beta-CD) and
      adamantane-terminated porphyrin derivatives bearing a disulfide bond (TPPC6-SS
      Ada). TPPC6-SS-Ada/PEG-beta-CD supramolecular amphiphiles can self-assemble into
      spherical micelles in water, and the assembled morphology was respectively
      characterized by transmission electron microscopy (TEM) and dynamic light
      scattering (DLS). Intracellular uptake and localization of supramolecular
      photosensitizers were further investigated by flow cytometry and confocal laser
      scanning microscopy (CLSM), and the result indicated that TPPC6-SS-Ada/PEG-beta
      CD micelles could be effectively up-taken by MCF-7 cells. Furthermore, the
      phototoxicity evaluated by an MTT assay showed that TPPC6-SS-Ada/PEG-beta-CD
      micelles have very low dark toxicity but greater photo-toxicity compared to free
      porphyrin. Thus, TPPC6-SS-Ada/PEG-beta-CD micelles would provide the potential
      application for photosensitizer delivery. 

PMID- 26222038
TI  - Modulation of neuronal network activity using magnetic nanoparticle-based
      astrocytic network integration.
AB  - Investigating the mechanisms of the neuron-glia interaction is important in the
      basic research of neuroscience and neural transplantation. Synaptic transmission
      is modulated by astrocyte activation in the pre- and post-synaptic terminals, and
      this phenomenon is spread to the surrounding astrocytes through gap junctions.
      However, the modulation of network-wide neuronal activity dependent on extensive
      astrocyte activation is not well understood. In this study, we show network-wide
      neuronal modulation associated with a newly developed three-dimensional neuronal
      and astrocytic network co-culture method. To establish widespread neuronal and
      astrocytic network interactions in vitro, we performed integration of magnetic
      nanoparticle-injected astrocytes (Mag-AS) onto the matured monolayer of neuronal
      networks using an external magnetic force. The neuronal electrical activity was
      dynamically synchronized at 24 h after integration of the Mag-AS network. In
      addition, Mag-AS network activation using a caged calcium compound rapidly
      induced suppression and subsequent synchronization of neuronal electrical
      activity. These results indicate that the high-density astrocytic network
      integration onto the neuronal network can induce widespread neuronal modulation,
      and our in vitro co-culture method contributes to the advancement of neuronal and
      astrocytic transplantation research. 

PMID- 26222039
TI  - 3D-printed dimethyloxallyl glycine delivery scaffolds to improve angiogenesis and
      osteogenesis.
AB  - Angiogenesis-osteogenesis coupling processes are vital in bone tissue
      engineering. Normal biomaterials implanted in bone defects have issues in the
      sufficient formation of blood vessels, especially in the central part. Single
      delivery of vascular endothelial growth factors (VEGF) to foci in previous
      studies did not show satisfactory results due to low loading doses, a short
      protein half-life and low efficiency. Development of a hypoxia-mimicking
      microenvironment for cells by local prolyl-4-hydroxylase inhibitor release, which
      can stabilize hypoxia-inducible factor 1alpha (HIF-1alpha) expression, is an
      alternative method. The aim of this study was to design a dimethyloxallyl glycine
      (DMOG) delivering scaffold composed of mesoporous bioactive glasses and poly(3
      hydroxybutyrate-co-3-hydroxyhexanoate) polymers (MPHS scaffolds), so as to
      investigate whether the sustained release of DMOG promotes local angiogenesis and
      bone healing. The morphology and microstructure of composite scaffolds were
      characterized. The DMOG release patterns from scaffolds loaded with different
      DMOG dosages were evaluated, and the effects of DMOG delivery on human bone
      marrow stromal cell (hBMSC) adhesion, viability, proliferation, osteogenic
      differentiation and angiogenic-relative gene expressions with scaffolds were also
      investigated. In vivo studies were carried out to observe vascular formations and
      new bone ingrowth with DMOG-loaded scaffolds. The results showed that DMOG could
      be released in a sustained manner over 4 weeks from MPHS scaffolds and obviously
      enhance the angiogenesis and osteogenesis in the defects. Microfil perfusion
      showed a significantly increased formation of vessels in the defects with DMOG
      delivery. Furthermore, micro-CT imaging and fluorescence labeling indicated
      larger areas of bone formation for DMOG-loaded scaffolds. It is concluded that
      MPHS-DMOG scaffolds are promising for enhancing bone healing of osseous defects. 

PMID- 26222040
TI  - Molecular Tools for Monitoring the Ecological Sustainability of a Stone Bio
      Consolidation Treatment at the Royal Chapel, Granada.
AB  - BACKGROUND: Biomineralization processes have recently been applied in situ to
      protect and consolidate decayed ornamental stone of the Royal Chapel in Granada
      (Spain). While this promising method has demonstrated its efficacy regarding
      strengthening of the stone, little is known about its ecological sustainability.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we report molecular monitoring of the stone
      autochthonous microbiota before and at 5, 12 and 30 months after the bio
      consolidation treatment (medium/long-term monitoring), employing the well-known
      molecular strategy of DGGE analyses. Before the bio-consolidation treatment, the
      bacterial diversity showed the exclusive dominance of Actinobacteria (100%),
      which decreased in the community (44.2%) after 5 months, and Gamma-proteobacteria
      (30.24%) and Chloroflexi (25.56%) appeared. After 12 months, Gamma-proteobacteria
      vanished from the community and Cyanobacteria (22.1%) appeared and remained
      dominant after thirty months, when the microbiota consisted of Actinobacteria
      (42.2%) and Cyanobacteria (57.8%) only. Fungal diversity showed that the
      Ascomycota phylum was dominant before treatment (100%), while, after five months,
      Basidiomycota (6.38%) appeared on the stone, and vanished again after twelve
      months. Thirty months after the treatment, the fungal population started to
      stabilize and Ascomycota dominated on the stone (83.33%) once again. Members of
      green algae (Chlorophyta, Viridiplantae) appeared on the stone at 5, 12 and 30
      months after the treatment and accounted for 4.25%, 84.77% and 16.77%,
      respectively. CONCLUSIONS: The results clearly show that, although a temporary
      shift in the bacterial and fungal diversity was observed during the first five
      months, most probably promoted by the application of the bio-consolidation
      treatment, the microbiota tends to regain its initial stability in a few months.
      Thus, the treatment does not seem to have any negative side effects on the stone
      autochthonous microbiota over that time. The molecular strategy employed here is
      suggested as an efficient monitoring tool to assess the impact on the stone
      autochthonous microbiota of the application of biomineralization processes as a
      restoration/conservation procedure.

PMID- 26222041
TI  - Chemical Component and Proteomic Study of the Amphibalanus (= Balanus) amphitrite
      Shell.
AB  - As typical biofoulers, barnacles possess hard shells and cause serious biofouling
      problems. In this study, we analyzed the protein component of the barnacle
      Amphibalanus (= Balanus) amphitrite shell using gel-based proteomics. The results
      revealed 52 proteins in the A. Amphitrite shell. Among them, 40 proteins were
      categorized into 11 functional groups based on KOG database, and the remaining 12
      proteins were unknown. Besides the known proteins in barnacle shell (SIPC,
      carbonic anhydrase and acidic acid matrix protein), we also identified chorion
      peroxidase, C-type lectin-like domains, serine proteases and proteinase inhibitor
      proteins in the A. Amphitrite shell. The sequences of these proteins were
      characterized and their potential functions were discussed. Histology and DAPI
      staining revealed living cells in the shell, which might secrete the shell
      proteins identified in this study.

PMID- 26222042
TI  - Micelle Structure and Hydrophobic Hydration.
AB  - Despite the ubiquity and utility of micelles self-assembled from aqueous
      surfactants, longstanding questions remain regarding their surface structure and
      interior hydration. Here we combine Raman spectroscopy with multivariate curve
      resolution (Raman-MCR) to probe the hydrophobic hydration of surfactants with
      various aliphatic chain lengths, and either anionic (carboxylate) or cationic
      (trimethylammonium) head groups, both below and above the critical micelle
      concentration. Our results reveal significant penetration of water into micelle
      interiors, well beyond the first few carbons adjacent to the headgroup. Moreover,
      the vibrational C-D frequency shifts of solubilized deuterated n-hexane confirm
      that it resides in a dry, oil-like environment (while the localization of
      solubilized benzene is sensitive to headgroup charge). Our findings imply that
      the hydrophobic core of a micelle is surrounded by a highly corrugated surface
      containing hydrated non-polar cavities whose depth increases with increasing
      surfactant chain length, thus bearing a greater resemblance to soluble proteins
      than previously recognized. 

PMID- 26222044
TI  - Patient-reported quality of life in a randomized placebo-controlled trial of
      naltrexone/bupropion for obesity.
AB  - Weight loss is associated with improved quality of life in some, but not all,
      weight loss trials. We evaluated changes at 56 weeks in quality of life, measured
      by the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire, in a
      pooled analysis of patient-level data from four randomized controlled Phase 3
      studies of naltrexone/bupropion (NB32 or Contrave(r)). The total number of
      subjects was 3362 (NB32 = 2043; placebo = 1319; mean body mass index = 36.3 kg
      m(2); mean age = 46). Improvements in IWQOL-Lite Total Score were greater in
      subjects treated with NB32 (11.9 points [SE 0.3]) vs. placebo (8.2 points [SE
      0.3]; P < 0.001), corresponding to weight reductions of 7.0% (SE 0.2) and 2.3%
      (SE 0.2), respectively. Greater improvements were also observed for NB32 vs.
      placebo on all five subscale scores of the IWQOL-Lite. Fifty per cent of NB32
      treated subjects achieved clinically meaningful improvements in IWQOL-Lite Total
      Score vs. 32.3% of placebo-treated subjects (odds ratio, 95% confidence interval;
      2.09, 1.79-2.44). Subjects losing the most weight (>= 15% of baseline weight)
      experienced the greatest improvement in IWQOL-Lite Total Score (19.3 points [SE
      0.7] for NB32 and 18.7 points [SE 1.3] for placebo; P = 0.624). Improved quality
      of life was associated with weight reduction and was achieved in more subjects
      treated with NB32 than placebo.

PMID- 26222043
TI  - Association Between Social Integration and Suicide Among Women in the United
      States.
AB  - IMPORTANCE: Suicide is one of the top 10 leading causes of mortality among middle
      aged women. Most work in the field emphasizes the psychiatric, psychological, or
      biological determinants of suicide. OBJECTIVE: To estimate the association
      between social integration and suicide. DESIGN, SETTING, AND PARTICIPANTS: We
      used data from the Nurses' Health Study, an ongoing nationwide prospective cohort
      study of nurses in the United States. Beginning in 1992, a population-based
      sample of 72 607 nurses 46 to 71 years of age were surveyed about their social
      relationships. The vital status of study participants was ascertained through
      June 1, 2010. EXPOSURES: Social integration was measured with a 7-item index that
      included marital status, social network size, frequency of contact with social
      ties, and participation in religious or other social groups. MAIN OUTCOMES AND
      MEASURES: The primary outcome of interest was suicide, defined as deaths
      classified using the codes E950 to E959 from the International Classification of
      Diseases, Eighth Revision. RESULTS: During more than 1.2 million person-years of
      follow-up (1992-2010), there were 43 suicide events. The incidence of suicide
      decreased with increasing social integration. In a multivariable Cox proportional
      hazards regression model, the relative hazard of suicide was lowest among
      participants in the highest category of social integration (adjusted hazard
      ratio, 0.23 [95% CI, 0.09-0.58]) and second-highest category of social
      integration (adjusted hazard ratio, 0.26 [95% CI, 0.09-0.74]). Increasing or
      consistently high levels of social integration were associated with a lower risk
      of suicide. These findings were robust to sensitivity analyses that accounted for
      poor mental health and serious physical illness. CONCLUSIONS AND RELEVANCE: Women
      who were socially well integrated had a more than 3-fold lower risk for suicide
      over 18 years of follow-up.

PMID- 26222045
TI  - Respiratory syncytial virus infection inhibits TLR4 signaling via up-regulation
      of miR-26b.
AB  - Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract
      illnesses in infants worldwide. TLR4 signal pathway plays a critical role in
      regulating immune response against RSV infection. However, the activation of TLR4
      in RSV infection is still unclear. In present study, the expression levels of miR
      26b and TLR4 mRNA were detected in peripheral blood mononuclear cells (PBMCs) of
      children with or without RSV infected bronchiolitis. The expression levels of
      TLR4 and its downstream genes IFNbeta and CCL5 were also quantified in PBMCs
      infected with RSVDeltaG or RSV A2 in vitro. The results showed that children with
      RSV infection had higher miR-26b level and lower TLR4 mRNA level in PBMCs. miR
      26b was predicted to target TLR4. In vitro, miR-26b mimic markedly down-regulated
      TLR4 mRNA/protein expression and IFNbeta/CCL5 concentrations while miR-26b
      inhibitor up-regulated these levels. This study reveals that RSV infection
      inhibits TLR4 signaling via up-regulation of miR-26b, which provides a potential
      therapeutic target for preventing and treating RSV infection. 

PMID- 26222046
TI  - Clinical evaluation of the shape of the suprascapular notch--an ultrasonographic
      and computed tomography comparative study: Application to shoulder pain
      syndromes.
AB  - The most common site of suprascapular nerve compression and injury is the
      suprascapular notch. The aim of this study was to assess the sensitivity and
      specificity of sonography in determining the type of suprascapular notch (SSN).
      Thirty randomized patients (60 upper extremities) underwent USG examination of
      the shoulder area. The results were further compared with three-dimensional
      reconstructions of the scapulae obtained through CT examination to place the SSNs
      within a fivefold classification. For identification of type I, the sensitivity
      was 73.3% and the specificity 97.8%. For identification of type III, the values
      was 96.9% and 85.7%, respectively. Type II was not found in USG examination.
      Discrimination between type IV and V was not possible. The mean distance between
      the line connecting the edges of the SSN and the skin was 38 mm in right-handed
      patients and 34 mm in ambidextrous subjects. Ultrasonographic examination of the
      SSN is characterized by high specificity for type I, and high sensitivity for
      type III SSN. Discrimination between type IV and V of the SSN is not recommended
      based on sonographic evaluation.

PMID- 26222048
TI  - NK cells modulate the lung dendritic cell-mediated Th1/Th17 immunity during
      intracellular bacterial infection.
AB  - The impact of the interaction between NK cells and lung dendritic cells (LDCs) on
      the outcome of respiratory infections is poorly understood. In this study, we
      investigated the effect and mechanism of NK cells on the function of LDCs during
      intracellular bacterial lung infection of Chlamydia muridarum in mice. We found
      that the naive mice receiving LDCs from C. muridarum-infected NK-cell-depleted
      mice (NK-LDCs) showed more serious body weight loss, bacterial burden, and
      pathology upon chlamydial challenge when compared with the recipients of LDCs
      from infected sham-treated mice (NK+LDCs). Cytokine analysis of the local tissues
      of the former compared with the latter exhibited lower levels of Th1 (IFN-gamma)
      and Th17 (IL-17), but higher levels of Th2 (IL-4), cytokines. Consistently, NK
      LDCs were less efficient in directing C. muridarum-specific Th1 and Th17
      responses than NK+LDCs when cocultured with CD4(+) T cells. In NK cell/LDC
      coculture experiments, the blockade of NKG2D receptor reduced the production of
      IL-12p70, IL-6, and IL-23 by LDCs. The neutralization of IFN-gamma in the culture
      decreased the production of IL-12p70 by LDCs, whereas the blockade of TNF-alpha
      resulted in diminished IL-6 production. Our findings demonstrate that NK cells
      modulate LDC function to elicit Th1/Th17 immunity during intracellular bacterial
      infection. 

PMID- 26222047
TI  - Outer Membrane Vesicle-Mediated Export of Processed PrtV Protease from Vibrio
      cholerae.
AB  - BACKGROUND: Outer membrane vesicles (OMVs) are known to release from almost all
      Gram-negative bacteria during normal growth. OMVs carry different biologically
      active toxins and enzymes into the surrounding environment. We suggest that OMVs
      may therefore be able to transport bacterial proteases into the target host
      cells. We present here an analysis of the Vibrio cholerae OMV-associated protease
      PrtV. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrated that PrtV
      was secreted from the wild type V. cholerae strain C6706 via the type II
      secretion system in association with OMVs. By immunoblotting and electron
      microscopic analysis using immunogold labeling, the association of PrtV with OMVs
      was examined. We demonstrated that OMV-associated PrtV was biologically active by
      showing altered morphology and detachment of cells when the human ileocecum
      carcinoma (HCT8) cells were treated with OMVs from the wild type V. cholerae
      strain C6706 whereas cells treated with OMVs from the prtV isogenic mutant showed
      no morphological changes. Furthermore, OMV-associated PrtV protease showed a
      contribution to bacterial resistance towards the antimicrobial peptide LL-37.
      CONCLUSION/SIGNIFICANCE: Our findings suggest that OMVs released from V. cholerae
      can deliver a processed, biologically active form of PrtV that contributes to
      bacterial interactions with target host cells.

PMID- 26222049
TI  - Morbidity after elective resection of prenatally diagnosed asymptomatic
      congenital pulmonary airway malformations.
AB  - BACKGROUND/AIM: The optimal management of prenatally diagnosed asymptomatic
      congenital pulmonary airway malformations (CPAM) is controversial. Since there is
      a paucity of data relating to surgical risks in this specific population, we
      reviewed our experience to further inform this controversy. METHODS: Ethically
      approved 10 year (2004-2013) retrospective review. Patients were included only if
      the CPAM was diagnosed prenatally and remained asymptomatic. Indication for
      surgery was physician recommendation and/or parental choice. MAIN RESULTS: Sixty
      patients were identified. Median age at surgery was 6.5 months (range 65 days to
      9.6 years). Resections were performed thoracoscopically (n = 51, one conversion)
      or by thoracotomy (n = 9). Surgical time was 2.5 hr (43 min to 4.75 hr). A chest
      drain was used in 58/60 and remained in situ 53 hr (23-108). There were no intra
      operative complications or blood transfusions. All patients were extubated at the
      end of the procedure with no re-intubations. Post-operative hospitalization was
      73.4 hr (23.8 hr to 4.2 days). Overall, complications occurred in 14/60 (23%).
      Eleven were minor but three were major: tension pneumothorax associated with new
      presentation of a small previously undiagnosed diaphragmatic hernia 5 days
      following resection; aggressive fibromatosis of the chest wall in the region
      close to resection 2 years later; and near-fatal hypovolemic cardiac arrest due
      to massive haemorrhage from a feeding vessel on postoperative day 7. There were
      no deaths and no cases of pleuropulmonary blastoma. CONCLUSION: Resection of
      prenatally diagnosed asymptomatic CPAM is associated with a significant risk of
      complications, which may be life threatening. These data contribute to a balanced
      discussion of risks and benefits for these children.

PMID- 26222050
TI  - Altered Brain Activation during Emotional Face Processing in Relation to Both
      Diagnosis and Polygenic Risk of Bipolar Disorder.
AB  - OBJECTIVES: Bipolar disorder (BD) is a highly heritable disorder with polygenic
      inheritance. Among the most consistent findings from functional magnetic imaging
      (fMRI) studies are limbic hyperactivation and dorsal hypoactivation. However, the
      relation between reported brain functional abnormalities and underlying genetic
      risk remains elusive. This is the first cross-sectional study applying a whole
      brain explorative approach to investigate potential influence of BD case-control
      status and polygenic risk on brain activation. METHODS: A BD polygenic risk score
      (PGRS) was estimated from the Psychiatric Genomics Consortium BD case-control
      study, and assigned to each individual in our independent sample (N=85 BD cases
      and 121 healthy controls (HC)), all of whom participated in an fMRI emotional
      faces matching paradigm. Potential differences in BOLD response across diagnostic
      groups were explored at whole-brain level in addition to amygdala as a region of
      interest. Putative effects of BD PGRS on brain activation were also investigated.
      RESULTS: At whole-brain level, BD cases presented with significantly lower
      cuneus/precuneus activation than HC during negative face processing (Z
      threshold=2.3 as cluster-level correction). The PGRS was associated positively
      with increased right inferior frontal gyrus (rIFG) activation during negative
      face processing. For amygdala activation, there were no correlations with
      diagnostic status or PGRS. CONCLUSIONS: These findings are in line with previous
      reports of reduced precuneus and altered rIFG activation in BD. While these
      results demonstrate the ability of PGRS to reveal underlying genetic risk of
      altered brain activation in BD, the lack of convergence of effects at diagnostic
      and PGRS level suggests that this relation is a complex one.

PMID- 26222052
TI  - Effect of ammonia stress on nitrogen metabolism of Ceratophyllum demersum.
AB  - The objective of the present study was to determine the effect of total ammonia N
      concentration and pH on N metabolism of Ceratophyllum demersum and to evaluate
      stress as a result of inorganic N enrichment in the water column on submerged
      macrophytes. Carefully controlled pH values distinguished between the effects of
      un-ionized NH3 and ionized NH4(+). The results showed that the most obvious
      consequence of ammonia addition was an overall increase in ammonia content and
      decrease in nitrate content in all tissues of fertilized plants. The activities
      of nitrate reductase and glutamine synthetase were inhibited by long-term ammonia
      addition. At the same time, ammonia addition significantly decreased soluble
      protein content and increased free amino acid content in all treatments. Another
      clear effect of ammonia addition was a decrease in carbon reserves. Therefore,
      the authors concluded that increased ammonia availability could affect plant
      survival and lead to a decline in C. demersum proliferation through a decrease in
      their carbon reserves. This interaction between N and C metabolism helps to
      explain changes in benthic vegetation as a result of steadily increasing coastal
      water eutrophication.

PMID- 26222051
TI  - Identification and Validation of a Potential Marker of Tissue Quality Using Gene
      Expression Analysis of Human Colorectal Tissue.
AB  - Correlative studies have identified numerous biomarkers that are individualizing
      therapy across many medical specialties, including oncology. Accurate
      interpretation of these studies requires the collection of tissue samples of
      sufficient quality. Tissue quality can be measured by changes in levels of gene
      expression and can be influenced by many factors including pre-analytical
      conditions, ischemic effects and the surgical collection procedure itself.
      However, as yet there are no reliable biomarkers of tissue quality at
      researchers' disposal. The aim of the current study was to identify genes with
      expression patterns that fluctuated reproducibly in response to typical post
      surgical stress (ischemia) in order to identify a specific marker of tissue
      quality. All tissue samples were obtained from patients with primary colorectal
      carcinoma (CRC) (N = 40) either via colonoscopy prior to surgery, or by surgical
      resection. Surgically resected tissue samples were divided into three groups and
      subjected to cold ischemia for 10, 20 or 45 minutes. Normal colorectal tissue and
      CRC tissue was analyzed using microarray and quantitative real-time PCR (qPCR).
      Comparing changes in gene expression between pre- and post-surgical tissue using
      microarray analysis identified a list of potential tissue quality biomarkers and
      this list was validated using qPCR. Results revealed that post-operative ischemia
      significantly alters gene expression in normal and CRC tissue samples. Both
      microarray analysis and qPCR revealed regulator of G-protein signaling 1 (RGS1)
      as a potential marker of CRC tissue quality and eukaryotic translation elongation
      factor 1 alpha 1 (EEF1A1) as a potential reference gene of post-operative tissue
      quality. Larger studies with additional time points and endpoints will be needed
      to confirm these results. 

PMID- 26222053
TI  - I Want More and Better Cells! - An Outreach Project about Stem Cells and Its
      Impact on the General Population.
AB  - Although science and technology impact every aspect of modern societies, there is
      still an extensive gap between science and society, which impairs the full
      exercise of citizenship. In the particular case of biomedical research increased
      investment should be accompanied by parallel efforts in terms of public
      information and engagement. We have carried out a project involving the
      production and evaluation of educational contents focused on stem cells -
      illustrated newspaper chronicles, radio interviews, a comic book, and animated
      videos - and monitored their impact on the Portuguese population. The study of
      the outreach materials in a heterogeneous sample of the population suggests that
      they are valuable tools to disseminate scientific messages, and that this is
      especially true for the comic-book format. Furthermore, the data showed that
      clear and stimulating outreach materials, that are able to teach new concepts and
      to promote critical thinking, increase engagement in science at different levels,
      depending on the depth of the concepts involved. Additionally, these materials
      can influence political, social and personal attitudes toward science. These
      results, together with the importance attributed to scientific research in stem
      cells by the population sampled, validates the diffusion of such materials as a
      significant contribution towards an overall public understanding and engagement
      in contemporary science, and this strategy should thus be considered in future
      projects. Regardless, stringent quality control must be implemented in order to
      efficiently communicate accurate scientific developments, and the public
      stimulated in terms of finding additional sources of reliable information. 

PMID- 26222055
TI  - Human Urinary Kallidinogenase Promotes Angiogenesis and Cerebral Perfusion in
      Experimental Stroke.
AB  - Angiogenesisis a key restorative mechanism in response to ischemia, and pro
      angiogenic therapy could be beneficial in stroke. Accumulating experimental and
      clinical evidence suggest that human urinary kallidinogenase (HUK) improves
      stroke outcome, but the underlying mechanisms are not clear. The aim of current
      study was to verify roles of HUK in post-ischemic angiogenesis and identify
      relevant mediators. In rat middle cerebral artery occlusion (MCAO) model, we
      confirmed that HUK treatment could improve stroke outcome, indicated by reduced
      infarct size and improved neurological function. Notably, the 18F-FDG micro-PET
      scan indicated that HUK enhanced cerebral perfusion in rats after MCAO treatment.
      In addition, HUK promotespost-ischemic angiogenesis, with increased vessel
      density as well as up-regulated VEGF andapelin/APJ expression in HUK-treated MCAO
      mice. In endothelial cell cultures, induction of VEGF and apelin/APJ expression,
      and ERK1/2 phosphorylation by HUK was further confirmed. These changes were
      abrogated by U0126, a selective ERK1/2 inhibitor. Moreover, F13A, a competitive
      antagonist of APJ receptor, significantly suppressed HUK-induced VEGF expression.
      Furthermore, angiogenic functions of HUK were inhibited in the presence of
      selective bradykinin B1 or B2 receptor antagonist both in vitro and in vivo. Our
      findings indicate that HUK treatment promotes post-ischemic angiogenesis and
      cerebral perfusion via activation of bradykinin B1 and B2 receptors, which is
      potentially due to enhancement expression of VEGF and apelin/APJ in ERK1/2
      dependent way. 

PMID- 26222054
TI  - Directed Differentiation of Human Embryonic Stem Cells into Prostate Organoids In
      Vitro and its Perturbation by Low-Dose Bisphenol A Exposure.
AB  - Studies using rodent and adult human prostate stem-progenitor cell models suggest
      that developmental exposure to the endocrine disruptor Bisphenol-A (BPA) can
      predispose to prostate carcinogenesis with aging. Unknown at present is whether
      the embryonic human prostate is equally susceptible to BPA during its natural
      developmental window. To address this unmet need, we herein report the
      construction of a pioneer in vitro human prostate developmental model to study
      the effects of BPA. The directed differentiation of human embryonic stem cells
      (hESC) into prostatic organoids in a spatial system was accomplished with precise
      temporal control of growth factors and steroids. Activin-induced definitive
      endoderm was driven to prostate specification by combined exposure to WNT10B and
      FGF10. Matrigel culture for 20-30 days in medium containing R-Spondin-1, Noggin,
      EGF, retinoic acid and testosterone was sufficient for mature prostate organoid
      development. Immunofluorescence and gene expression analysis confirmed that
      organoids exhibited cytodifferentiation and functional properties of the human
      prostate. Exposure to 1 nM or 10 nM BPA throughout differentiation culture
      disturbed early morphogenesis in a dose-dependent manner with 1 nM BPA increasing
      and 10 nM BPA reducing the number of branched structures formed. While
      differentiation of branched structures to mature organoids seemed largely
      unaffected by BPA exposure, the stem-like cell population increased, appearing as
      focal stem cell nests that have not properly entered lineage commitment rather
      than the rare isolated stem cells found in normally differentiated structures.
      These findings provide the first direct evidence that low-dose BPA exposure
      targets hESC and perturbs morphogenesis as the embryonic cells differentiate
      towards human prostate organoids, suggesting that the developing human prostate
      may be susceptible to disruption by in utero BPA exposures. 

PMID- 26222056
TI  - Potential Effect of Physical Activity Calorie Equivalent (PACE) Labeling on Adult
      Fast Food Ordering and Exercise.
AB  - INTRODUCTION: Numeric calorie content labels show limited efficacy in reducing
      the number of calories ordered from fast food meals. Physical activity calorie
      equivalent (PACE) labels are an alternative that may reduce the number of
      calories ordered in fast food meals while encouraging patrons to exercise.
      METHODS: A total of 1000 adults from 47 US states were randomly assigned via
      internet survey to one of four generic fast food menus: no label, calories only,
      calories + minutes, or calories + miles necessary to walk to burn off the
      calories. After completing hypothetical orders participants were asked to rate
      the likelihood of calorie-only and PACE labels to influence (1) food choice and
      (2) physical activity. RESULTS: Respondents (n = 823) ordered a median of 1580
      calories from the no-label menu, 1200 from the calories-only menu, 1140 from the
      calories + minutes menu, and 1210 from the calories + miles menu (p = 0.0001).
      40% of respondents reported that PACE labels were "very likely" to influence food
      item choice vs. 28% for calorie-only labels (p<0.0001). 64% of participants
      reported that PACE labels were "somewhat likely" or "very likely" to influence
      their level of physical activity vs. 49% for calorie-only labels (p<0.0001).
      CONCLUSIONS: PACE labels may be helpful in reducing the number of calories
      ordered in fast food meals and may have the added benefit of encouraging
      exercise.

PMID- 26222058
TI  - Correction: Accurate, Fully-Automated NMR Spectral Profiling for Metabolomics.

PMID- 26222057
TI  - Genome Wide Association Study for Predictors of Progression Free Survival in
      Patients on Capecitabine, Oxaliplatin, Bevacizumab and Cetuximab in First-Line
      Therapy of Metastatic Colorectal Cancer.
AB  - PURPOSE: Despite expanding options for systemic treatment, survival for
      metastatic colorectal cancer (mCRC) remains limited and individual response is
      difficult to predict. In search of pre-treatment predictors, pharmacogenetic
      research has mainly used a candidate gene approach. Genome wide association (GWA)
      studies offer the benefit of simultaneously analyzing a large number of SNPs, in
      both known and still unidentified functional regions. Using a GWA approach, we
      searched for genetic markers affecting progression free survival (PFS) in mCRC
      patients treated with first-line capecitabine, oxaliplatin and bevacizumab (CAPOX
      B), with or without cetuximab. PATIENTS AND METHODS: 755 patients were included
      in the CAIRO2-trial, a multicenter phase III trial, randomizing between first
      line treatment with CAPOX-B versus CAPOX-B plus cetuximab. Germline DNA and
      complete clinical information was available from 553 patients and genome wide
      genotyping was performed, using Illumina's OmniExpress beadchip arrays, with
      647,550 markers passing all quality checks. Another 2,202,473 markers were
      imputated by using HapMap2. Association with PFS was analysed using a Cox
      proportional hazards model. RESULTS: One marker, rs885036, associated
      significantly with PFS (P = 2.17x10(-8)) showing opposite effects on PFS
      depending on treatment arm. The minor allele was associated with increased PFS in
      patients receiving cetuximab. A cluster of markers located on chromosome 8
      associated with PFS, irrespective of treatment arm (P-values of 2.30x10(-7) to
      1.04x10(-6)). CONCLUSION: This is the first GWA study to find SNPs affecting PFS
      in mCRC patients treated with CAPOX-B, either with or without cetuximab. Rs885036
      is a potential predictive marker for cetuximab efficacy. These markers need to be
      validated in independent treatment cohorts.

PMID- 26222059
TI  - The Fixation Distance to the Stimulus Influences ERP Quality: An EEG and Eye
      Tracking N400 Study.
AB  - In a typical visual Event Related Potential (ERP) study, the stimulus is
      presented centrally on the screen. Normally an ERP response will be measured
      provided that the participant directs their gaze towards the stimulus. The aim of
      this study was to assess how the N400 component of an ERP was affected when the
      stimulus was presented in the foveal, parafoveal or peripheral vision of the
      participant's visual field. Utilizing stimuli that have previously produced an
      N400 response to action incongruities, the same stimuli sequences were presented
      at 0 degrees , 4 degrees , 8 degrees  and 12 degrees  of visual angle from a
      fixation location. In addition to the EEG data, eye tracking data were recorded
      to act as a fixation control method and to allow for eye artifact detection. The
      results show a significant N400 effect in the right parieto-temporal electrodes
      within the 0 degrees  visual angle condition. For the other conditions, the N400
      effect was reduced (4 degrees ) or not present (8 degrees  and 12 degrees ). Our
      results suggest that the disappearance of the N400 effect with eccentricity is
      due to the fixation distance to the stimulus. However, variables like attentional
      allocation could have also had an impact on the results. This study highlights
      the importance of presenting a stimulus within the foveal vision of the
      participant in order to maximize ERP effects related to higher order cognitive
      processes.

PMID- 26222061
TI  - Predictors of Pertussis Polymerase Chain Reaction Positive Results in Minnesota,
      2005-2009.
AB  - Predictors of polymerase chain reaction (PCR) positivity for pertussis were
      assessed using Minnesota active surveillance data. Report of an exposure to
      pertussis and testing within the optimal time frame of <=2 weeks were
      significantly associated with testing PCR positive, emphasizing the importance of
      asking about epidemiological factors when assessing patients for pertussis, and
      timely PCR testing. 

PMID- 26222060
TI  - Survival Benefit of Empirical Therapy for Staphylococcus aureus Bloodstream
      Infections in Infants.
AB  - BACKGROUND: The impact of early adequate empirical antibiotic therapy on outcomes
      of infants in the neonatal intensive care unit (NICU) who develop Staphylococcus
      aureus bloodstream infections (BSI) is unknown. METHODS: Infants with S. aureus
      BSI discharged in 1997-2012 from 348 NICUs managed by the Pediatrix Medical Group
      were identified. Early adequate empirical antibiotic therapy was defined as
      exposure to >=1 antibiotic with anti-staphylococcal activity on the day the first
      positive blood culture was obtained. All other cases were defined as inadequate
      empirical antibiotic therapy. We evaluated the association between inadequate
      empirical antibiotic therapy on outcomes controlling for gestational age, small
      for gestational age status, gender, discharge year, mechanical ventilation,
      inotropic support and use of supplemental oxygen. The primary outcome was 30-day
      mortality. Secondary outcomes were 7-day mortality, death before hospital
      discharge and length of bacteremia. RESULTS: Of the 3339 infants with S. aureus
      BSI, 2492 (75%) had methicillin-susceptible S. aureus (MSSA) BSI and 847 (25%)
      had methicillin-resistant S. aureus (MRSA) BSI. Inadequate empirical antibiotic
      therapy was administered in 725 (22%) cases. Inadequate empirical antibiotic
      therapy was associated with increased 30-day mortality (odds ratio: 2.03; 95%
      confidence interval: 1.08-3.82) among infants with MRSA BSI. Inadequate empirical
      antibiotic therapy was not associated with increases in mortality among infants
      with MSSA BSI. CONCLUSIONS: After controlling for confounders, inadequate
      empirical antibiotic therapy was associated with a modestly increased mortality
      at 30 days for infants with MRSA BSI.

PMID- 26222062
TI  - Oropharyngeal Carriage of Meningococcus in Portugal by Group and Clonal Complex 6
      Years After Adolescent Vaccine Campaign.
AB  - Portugal introduced (2+1) conjugate Meningococcal group C vaccine in 2006 with
      high coverage catch up to 18 years and has given only 1 dose at 1 year since
      2012. Among 601 student oropharyngeal swabs, meningococcal carriage rate was
      13.3% (A-0%, B-5.3%, C-0.3%, W-0.2%, X-0.2% and Y-1.7%). C and W strains were of
      potentially disease-causing clonal complexes (cc) but not the hyperinvasive cc11.

PMID- 26222063
TI  - Prevalence, Risk Factors and Molecular Characteristics of Meningococcal Carriage
      Among Brazilian Adolescents.
AB  - BACKGROUND: In 2010, introduction of the meningococcal C conjugate vaccine in
      Brazil for children <2 years provided an immediate reduction in the incidence
      rates of disease among the age groups targeted for the vaccine, but no early
      impact was observed in unvaccinated age groups. Knowledge about meningococcal
      carriage is crucial for improving our understanding of the disease epidemiology
      and for designing effective vaccination programs. Taking in account the very
      limited published data currently available describing meningococcal carriage in
      Brazil, we performed a study to evaluate the prevalence of Neisseria meningitidis
      carriage among adolescent students. METHODS: A cross-sectional study was
      conducted in 2012 to assess the prevalence of meningococcal carriage among a
      representative sample of 1208 students 11-19 years of age in Campinas, Brazil.
      Genotypic and phenotypic characterization of isolated carriage strains and the
      effect of potential risk factors for carriage were also analyzed. RESULTS: The
      overall carriage prevalence was 9.9% (95% confidence interval, 8.3-11.8%), with
      dominance of serogroup C (1.32%), followed by serogroups B (0.99%), E (0.74%), Y
      (0.49%) and W (0.25%). A lower level of education of the parents was
      independently associated with a higher risk of carriage. A high diversity of
      genotypes was found among carriage strains. CONCLUSIONS: The evidence gathered
      during this study provides estimates of carriage prevalence in Brazilian
      adolescents, showing an unusually high dominance of serogroup C. These results
      have important implications in future strategies to optimize the impact of the
      current meningococcal C vaccination program in Brazil.

PMID- 26222064
TI  - The Positive Predictive Value of Lyme Elisa for the Diagnosis of Lyme Disease in
      Children.
AB  - By using a Lyme enzyme-linked immunosorbent assay (ELISA), we demonstrated that
      high ELISA index values are strongly predictive of Lyme disease. In children with
      clinical presentations consistent with Lyme disease, ELISA index values >=3.0 had
      a positive predictive value of 99.4% (95% confidence interval: 98.1-99.8%) for
      Lyme disease, making a supplemental Western immunoblot potentially unnecessary. 

PMID- 26222065
TI  - Early Differentiation of Kawasaki Disease Shock Syndrome and Toxic Shock Syndrome
      in a Pediatric Intensive Care Unit.
AB  - BACKGROUND: Kawasaki disease shock syndrome (KDSS) and toxic shock syndrome (TSS)
      can present as shock and fever with skin rash, but the management of these 2
      groups of patients is different. This report proposes to help clinicians earlier
      distinguish these 2 diseases and expedite institution of appropriate therapy.
      METHODS: We retrospectively reviewed the medical records of patients admitted to
      the pediatric intensive care unit with the diagnosis of KDSS or TSS from January
      2000 through December 2010. Clinical, laboratory and echocardiographic data were
      collected for analysis of differences between them. RESULTS: Seventeen patients
      met the inclusion criteria of KDSS and 16 had a confirmed diagnosis of TSS. The
      mean age of the KDSS group was significantly younger than that of the TSS group
      (36.8 +/- 41.1 vs. 113.3 +/- 55.6 months, P < 0.001). Significantly lower
      hemoglobulin and age-adjusted hemoglobulin concentrations were noted in the KDSS
      group [Hb, age-adjusted Z score, -1.88 (range, -3.9 to 3.9) vs. 0.89 (range, -6.4
      to 10.8), P = 0.006]. The median platelet count of the KDSS group was nearly
      twice that of the TSS group [312 * 103 per MUL (range, 116-518) vs. 184.5 * 103
      per MUL (range: 31-629), P = 0.021]. Echocardiographic abnormalities, such as
      valvulitis (mitral or tricuspid regurgitation) and coronary artery lesions, were
      significantly more common in the KDSS group (P = 0.022). CONCLUSIONS:
      Echocardiography, anemia and thrombocytosis are useful early differentiating
      features between KDSS and TSS patients.

PMID- 26222066
TI  - A Novel Antiviral Target Structure Involved in the RNA Binding, Dimerization, and
      Nuclear Export Functions of the Influenza A Virus Nucleoprotein.
AB  - Developing antiviral therapies for influenza A virus (IAV) infection is an
      ongoing process because of the rapid rate of antigenic mutation and the emergence
      of drug-resistant viruses. The ideal strategy is to develop drugs that target
      well-conserved, functionally restricted, and unique surface structures without
      affecting host cell function. We recently identified the antiviral compound,
      RK424, by screening a library of 50,000 compounds using cell-based infection
      assays. RK424 showed potent antiviral activity against many different subtypes of
      IAV in vitro and partially protected mice from a lethal dose of A/WSN/1933 (H1N1)
      virus in vivo. Here, we show that RK424 inhibits viral ribonucleoprotein complex
      (vRNP) activity, causing the viral nucleoprotein (NP) to accumulate in the cell
      nucleus. In silico docking analysis revealed that RK424 bound to a small pocket
      in the viral NP. This pocket was surrounded by three functionally important
      domains: the RNA binding groove, the NP dimer interface, and nuclear export
      signal (NES) 3, indicating that it may be involved in the RNA binding,
      oligomerization, and nuclear export functions of NP. The accuracy of this binding
      model was confirmed in a NP-RK424 binding assay incorporating photo-cross-linked
      RK424 affinity beads and in a plaque assay evaluating the structure-activity
      relationship of RK424. Surface plasmon resonance (SPR) and pull-down assays
      showed that RK424 inhibited both the NP-RNA and NP-NP interactions, whereas size
      exclusion chromatography showed that RK424 disrupted viral RNA-induced NP
      oligomerization. In addition, in vitro nuclear export assays confirmed that RK424
      inhibited nuclear export of NP. The amino acid residues comprising the NP pocket
      play a crucial role in viral replication and are highly conserved in more than
      7,000 NP sequences from avian, human, and swine influenza viruses. Furthermore,
      we found that the NP pocket has a surface structure different from that of the
      pocket in host molecules. Taken together, these results describe a promising new
      approach to developing influenza virus drugs that target a novel pocket structure
      within NP. 

PMID- 26222067
TI  - Robustness of Next Generation Sequencing on Older Formalin-Fixed Paraffin
      Embedded Tissue.
AB  - Next Generation Sequencing (NGS) technologies are used to detect somatic
      mutations in tumors and study germ line variation. Most NGS studies use DNA
      isolated from whole blood or fresh frozen tissue. However, formalin-fixed
      paraffin-embedded (FFPE) tissues are one of the most widely available clinical
      specimens. Their potential utility as a source of DNA for NGS would greatly
      enhance population-based cancer studies. While preliminary studies suggest FFPE
      tissue may be used for NGS, the feasibility of using archived FFPE specimens in
      population based studies and the effect of storage time on these specimens needs
      to be determined. We conducted a study to determine whether DNA in archived FFPE
      high-grade ovarian serous adenocarcinomas from Surveillance, Epidemiology and End
      Results (SEER) registries Residual Tissue Repositories (RTR) was present in
      sufficient quantity and quality for NGS assays. Fifty-nine FFPE tissues, stored
      from 3 to 32 years, were obtained from three SEER RTR sites. DNA was extracted,
      quantified, quality assessed, and subjected to whole exome sequencing (WES).
      Following DNA extraction, 58 of 59 specimens (98%) yielded DNA and moved on to
      the library generation step followed by WES. Specimens stored for longer periods
      of time had significantly lower coverage of the target region (6% lower per 10
      years, 95% CI: 3-10%) and lower average read depth (40x lower per 10 years, 95%
      CI: 18-60), although sufficient quality and quantity of WES data was obtained for
      data mining. Overall, 90% (53/59) of specimens provided usable NGS data
      regardless of storage time. This feasibility study demonstrates FFPE specimens
      acquired from SEER registries after varying lengths of storage time and under
      varying storage conditions are a promising source of DNA for NGS. 

PMID- 26222068
TI  - Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute
      Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia.
AB  - BACKGROUND: KRAS and NRAS gene mutations are frequently observed in childhood
      leukemia. The objective of this study was to determine the frequency of RAS
      mutations and the association between RAS mutations and other genetic aberrations
      in Arab Asian children with acute lymphoblastic leukemia (ALL) or acute myeloid
      leukemia (AML). METHODS: Diagnostic samples of 485 patients (<18 years) with
      acute leukemia from Iraq and Jordan were obtained, using Flinders Technology
      Associates filter papers. Polymerase chain reaction and direct sequencing were
      performed in Japan. RESULTS: RAS mutations were detected in 86/318 (27%) of ALL
      cases and 35/167 (21%) of AML cases. The frequency of NRAS mutation was similar
      to that of KRAS mutation in ALL. Two RAS mutations were detected in nine
      patients. Among 264 Iraqi patients with ALL, RAS mutation was significantly
      associated with lower initial white blood cell count. Of 57 patients with
      chimeric transcripts, only two patients with either TEL-AML1 or E2A-PBX1 had KRAS
      mutation. The frequency of NRAS mutation was four times higher than that of KRAS
      mutation in AML. FAB-M4 and M5 subsets were associated with RAS mutation. Among
      134 Iraqi patients with AML, 18 patients had RAS mutations and other genetic
      aberrations. In particular, 9 of 25 (36%) with MLL-rearrangement had RAS
      mutations. CONCLUSION: The prevalence of oncogenic RAS mutations was higher among
      Arab Asian children than in other countries. RAS mutations in AML were found to
      coexist with other genetic aberrations, particularly MLL rearrangement.

PMID- 26222069
TI  - Hotspots of Community Change: Temporal Dynamics Are Spatially Variable in
      Understory Plant Composition of a California Oak Woodland.
AB  - Community response to external drivers such climate and disturbance can lead to
      fluctuations in community composition, or to directional change. Temporal
      dynamics can be influenced by a combination of drivers operating at multiple
      spatial scales, including external landscape scale drivers, local abiotic
      conditions, and local species pools. We hypothesized that spatial variation in
      these factors can create heterogeneity in temporal dynamics within landscapes. We
      used understory plant species composition from an 11 year dataset from a
      California oak woodland to compare plots where disturbance was experimentally
      manipulated with the removal of livestock grazing and a prescribed burn. We
      quantified three properties of temporal variation: compositional change
      (reflecting the appearance and disappearance of species), temporal fluctuation,
      and directional change. Directional change was related most strongly to
      disturbance type, and was highest at plots where grazing was removed during the
      study. Temporal fluctuations, compositional change, and directional change were
      all related to intrinsic abiotic factors, suggesting that some locations are more
      responsive to external drivers than others. Temporal fluctuations and
      compositional change were linked to local functional composition, indicating that
      environmental filters can create subsets of the local species pool that do not
      respond in the same way to external drivers. Temporal dynamics are often assumed
      to be relatively static at the landscape scale, provided disturbance and climate
      are continuous. This study shows that local and landscape scale factors jointly
      influence temporal dynamics creating hotspots that are particularly responsive to
      climate and disturbance. Thus, adequate predictions of response to disturbance or
      to changing climate will only be achieved by considering how factors at multiple
      spatial scales influence community resilience and recovery. 

PMID- 26222070
TI  - The 5'-AMP-Activated Protein Kinase (AMPK) Is Involved in the Augmentation of
      Antioxidant Defenses in Cryopreserved Chicken Sperm.
AB  - Semen cryopreservation is a unique tool for the management of animal genetic
      diversity. However, the freeze-thaw process causes biochemical and physical
      alterations which make difficult the restoration of sperm energy-dependent
      functions needed for fertilization. 5'-AMP activated protein kinase (AMPK) is a
      key sensor and regulator of intracellular energy metabolism. Mitochondria
      functions are known to be severely affected during sperm cryopreservation with
      deleterious oxidative and peroxidative effects leading to cell integrity and
      functions damages. The aim of this study was thus to examine the role of AMPK on
      the peroxidation/antioxidant enzymes defense system in frozen-thawed sperm and
      its consequences on sperm functions. Chicken semen was diluted in media
      supplemented with or without AMPK activators (AICAR or Metformin [MET]) or
      inhibitor (Compound C [CC]) and then cryopreserved. AMPKalpha phosphorylation,
      antioxidant enzymes activities, mitochondrial potential, ATP, citrate, viability,
      acrosome reaction ability (AR) and various motility parameters were negatively
      affected by the freeze-thaw process while reactive oxygen species (ROS)
      production, lipid peroxidation (LPO) and lactate concentration were dramatically
      increased. AICAR partially restored superoxide dismutase (SOD), Glutathione
      Peroxidase (GPx) and Glutathione Reductase (GR), increased ATP, citrate, and
      lactate concentration and subsequently decreased the ROS and LPO
      (malondialdehyde) in frozen-thawed semen. Motility parameters were increased
      (i.e., + 23% for motility, + 34% for rapid sperm) as well as AR (+ 100%). MET had
      similar effects as AICAR except that catalase activity was restored and that ATP
      and mitochondrial potential were further decreased. CC showed effects opposite to
      AICAR on SOD, ROS, LPO and AR and motility parameters. Taken together, our
      results strongly suggest that, upon freeze-thaw process, AMPK stimulated
      intracellular anti-oxidative defense enzymes through ATP regulation, thus
      reducing ROS and lipid peroxidation, and consequently partially restoring several
      essential sperm functions and leading to a better quality of cryopreserved sperm.

PMID- 26222071
TI  - Comprehensive Molecular Profiling of Archival Bone Marrow Trephines Using a
      Commercially Available Leukemia Panel and Semiconductor-Based Targeted
      Resequencing.
AB  - Comprehensive mutation profiling becomes more and more important in
      hematopathology complementing morphological and immunohistochemical evaluation of
      fixed, decalcified and embedded bone marrow biopsies for diagnostic, prognostic
      and also predictive purposes. However, the number and the size of relevant genes
      leave conventional Sanger sequencing impracticable in terms of costs, required
      input DNA, and turnaround time. Since most published protocols and commercially
      available reagents for targeted resequencing of gene panels are established and
      validated for the analysis of fresh bone marrow aspirate or peripheral blood it
      remains to be proven whether the available technology can be transferred to the
      analysis of archival trephines. Therefore, the performance of the recently
      available Ion AmpliSeq AML Research panel (LifeTechnologies) was evaluated for
      the analysis of fragmented DNA extracted from archival bone marrow trephines.
      Taking fresh aspirate as gold standard all clinically relevant mutations (n = 17)
      as well as 25 well-annotated SNPs could be identified reliably with high quality
      in the corresponding archival trephines of the training set (n = 10). Pre
      treatment of the extracted DNA with Uracil-DNA-Glycosylase reduced the number of
      low level artificial sequence variants by more than 60%, vastly reducing time
      required for proper evaluation of the sequencing results. Subsequently, randomly
      picked FFPE samples (n = 41) were analyzed to evaluate sequencing performance
      under routine conditions. Thereby all known mutations (n = 43) could be verified
      and 36 additional mutations in genes not yet covered by the routine work-up
      (e.g., TET2, ASXL1, DNMT3A), demonstrating the feasibility of this approach and
      the gain of diagnostically relevant information. The dramatically reduced amount
      of input DNA, the increase in sensitivity as well as calculated cost
      effectiveness, low hands on , and turn-around-time, necessary for the analysis of
      237 amplicons strongly argue for replacing Sanger sequencing by this
      semiconductor-based targeted resequencing approach. 

PMID- 26222072
TI  - From the Guest Editors: Role of Tumor Microenvironment in Tumor Progression and
      Treatment Response: A 30 Years' Journey.

PMID- 26222073
TI  - Tumor Stroma, Tumor Blood Vessels, and Antiangiogenesis Therapy.
AB  - Solid tumors generally require a vascularized connective tissue stroma if they
      are to grow beyond minimal size. They generate that stroma in part by secreting
      vascular endothelial growth factor (VEGF), a potent vascular permeability and
      angiogenic factor. Increased vascular permeability leads to deposition of a
      provisional fibrin stroma, which supports tumor, connective tissue, and
      inflammatory cell migration and plays an active role in the formation of mature
      vascularized stroma. Vascular endothelial growth factor-induced tumor blood
      vessels are heterogeneous, of at least 6 distinct types, and develop linearly
      over time. They include both angiogenic (mother vessels, glomeruloid
      microvascular proliferations, vascular malformations, capillaries) and
      arteriovenogenic (feeding arteries, draining veins) blood vessels. Attacking the
      tumor vasculature with drugs that target VEGF or its receptors (VEGFR) has come
      into vogue but has been less effective than had been hope for. One reason for
      this is that anti-VEGF/VEGFR therapy attacks only a subset of tumor blood
      vessels, the earliest to form. New targets on late-forming blood vessels such as
      feeding arteries would be useful in helping antivascular cancer therapy fulfill
      its promise. 

PMID- 26222074
TI  - Endothelial Metabolism Driving Angiogenesis: Emerging Concepts and Principles.
AB  - Angiogenesis has been traditionally studied by focusing on growth factors and
      other proangiogenic signals, but endothelial cell (EC) metabolism has not
      received much attention. Nonetheless, glycolysis, one of the major metabolic
      pathways that converts glucose to pyruvate, is required for the phenotypic switch
      from quiescent to angiogenic ECs. During vessel sprouting, the glycolytic
      activator PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3)
      promotes vessel branching by rendering ECs more competitive to reach the tip of
      the vessel sprout, whereas fatty acid oxidation selectively regulates
      proliferation of endothelial stalk cells. These studies show that metabolic
      pathways in ECs regulate vessel sprouting, more importantly than anticipated.
      This review discusses the recently discovered role of glycolysis and fatty acid
      oxidation in vessel sprouting. We also highlight how metabolites can influence EC
      behavior as signaling molecules by modulating posttranslational modification. 

PMID- 26222076
TI  - Mechanisms of Drug Resistance Related to the Microenvironment of Solid Tumors and
      Possible Strategies to Inhibit Them.
AB  - Drug resistance can occur at the individual cellular level or as a result of
      properties of the tumor microenvironment. The convoluted vasculature within
      tumors results in robustly proliferating well-nourished cells located proximal to
      functional blood vessels and regions of slowly proliferating (often hypoxic)
      cells located distal to functional blood vessels. Irregular blood flow and large
      distances between functional blood vessels in solid tumors lead to poor drug
      distribution within them such that cells distal from functional blood vessels are
      exposed to ineffective concentrations of drug, resulting in therapeutic
      resistance. Strategies to improve or complement the distribution of anticancer
      drugs within tumors hold promise for increasing antitumor effects without
      corresponding increases in normal tissue toxicity. In particular, use of hypoxia
      targeted agents and modulation of autophagy have shown promising results in
      enhancing the distribution of drug activity within solid tumors and hence
      antitumor efficacy. In this review, we describe causes of resistance to
      chemotherapy that relate to the microenvironment of solid tumors and the
      potential to improve antitumor effects by countering such mechanisms of
      resistance. 

PMID- 26222075
TI  - The Role of Stroma in Tumor Development.
AB  - The tumor microenvironment plays an essential role in various stages of cancer
      development. This environment, composed of the extracellular matrix, fibroblasts,
      endothelial cells, and cells of the immune system regulates the behavior of and
      co-evolve with tumor cells. Many of the components, including the innate and
      adaptive immune cells, play multifaceted roles during cancer progression and can
      promote or inhibit tumor development, depending on local and systemic conditions.
      Interestingly, a strategy by which tumor cells gain drug resistance is by
      modifying the tumor microenvironment. Together, understanding the mechanisms by
      which the tumor microenvironment functions should greatly facilitate the
      development of new therapeutic interventions by targeting the tumor niche. 

PMID- 26222077
TI  - The National Cancer Institute's Efforts in Promoting Research in the Tumor
      Microenvironment.
AB  - The National Cancer Institute has fostered studies of the tumor microenvironment
      since 1993. Current funding initiatives that span concepts in cancer biology,
      technology development, convergence of physical sciences-oncology, and systems
      biology all support research that help in our understanding of the role of the
      tumor microenvironment at all stages of cancer progression and therapeutic
      resistance. 

PMID- 26222078
TI  - The Contribution of Angiogenesis to the Process of Metastasis.
AB  - The role of angiogenesis in tumor growth has been studied continuously for over
      45 years. It is now appreciated that angiogenesis is also essential for the
      dissemination and establishment of tumor metastases. In this review, we focus on
      the role of angiogenesis as a necessity for the escape of tumor cells into the
      bloodstream and for the establishment of metastatic colonies in secondary sites.
      We also discuss the role of tumor lymphangiogenesis as a means of dissemination
      of lymphatic metastases. Appropriate combination therapies may be used in the
      future to both prevent and treat metastatic disease through the rational use of
      antiangiogenic and antilymphangiogenic therapies in ways that are informed by the
      current and future work in the field. 

PMID- 26222079
TI  - A Decade of Experience in Developing Preclinical Models of Advanced- or Early
      Stage Spontaneous Metastasis to Study Antiangiogenic Drugs, Metronomic
      Chemotherapy, and the Tumor Microenvironment.
AB  - The clinical circumstance of treating spontaneous metastatic disease, after
      resection of primary tumors, whether advanced/overt or microscopic in nature, is
      seldom modeled in mice and may be a major factor in explaining the frequent
      discordance between preclinical and clinical therapeutic outcomes where the trend
      is "overprediction" of positive results in preclinical mouse model studies. To
      evaluate this hypothesis, a research program was initiated a decade ago to
      develop multiple models of metastasis in mice, using variants of human tumor cell
      lines selected in vivo for enhanced spontaneous metastatic aggressiveness after
      surgical resection of established orthotopic primary tumors. These models have
      included breast, renal, and colorectal carcinomas; ovarian cancer (but without
      prior surgery); and malignant melanoma. They have been used primarily for
      experimental therapeutic investigations involving various antiangiogenic drugs
      alone or with chemotherapy, especially "metronomic" low-dose chemotherapy. The
      various translational studies undertaken have revealed a number of clinically
      relevant findings. These include the following: (i) the potential of metronomic
      chemotherapy, especially when combined with a vascular endothelial growth factor
      pathway targeting drug to successfully treat advanced metastatic disease; (ii)
      the development of relapsed spontaneous brain metastases in mice with melanoma or
      breast cancer whose systemic metastatic disease is successfully controlled for a
      period with a given therapy; (iii) foreshadowing the failure of adjuvant
      antiangiogenic drug-based phase III trials; (iv) recapitulating the failure of
      oral antiangiogenic tyrosine kinase inhibitors plus standard chemotherapy in
      contrast to the modest successes of antiangiogenic antibodies plus chemotherapy
      in metastatic breast cancer; and (v) revealing "vessel co-option" and absence of
      angiogenesis as a determinant of intrinsic resistance or minimal responsiveness
      to antiangiogenic therapy in lung metastases. Developing similar models of
      metastatic disease but involving mouse tumors grown in syngeneic immunocompetent
      mice may also prove useful for future translational studies of immune therapy
      based treatments. 

PMID- 26222080
TI  - The Biology of Brain Metastasis: Challenges for Therapy.
AB  - Many patients with lung cancer, breast cancer, and melanoma develop brain
      metastases that are resistant to conventional therapy. The median survival for
      untreated patients is 1 to 2 months, which may be extended to 6 months with
      surgery, radiotherapy, and chemotherapy. The outcome of metastasis depends on
      multiple interactions of unique metastatic cells with host homeostatic mechanisms
      which the tumor cells exploit for their survival and proliferation. The blood
      brain barrier is leaky in metastases that are larger than 0.5-mm diameter because
      of production of vascular endothelial growth factor by metastatic cells. Brain
      metastases are surrounded and infiltrated by microglia and activated astrocytes.
      The interaction with astrocytes leads to up-regulation of multiple genes in the
      metastatic cells, including several survival genes that are responsible for the
      increased resistance of tumor cells to cytotoxic drugs. These findings
      substantiate the importance of the "seed and soil" hypothesis and that successful
      treatment of brain metastases must include targeting of the organ
      microenvironment. 

PMID- 26222081
TI  - Targeted Therapy for Cancer in the Genomic Era.
AB  - The advent of cancer genomics has led to the development of many highly
      successful targeted therapies, primarily inhibitors of growth factor receptors
      and related kinases, including imatinib for chronic myeloid leukemia and
      trastuzumab for HER2-positive breast cancer. This approach has become highly
      successful for certain cancers. However, as the list of targeted therapies
      expands, their efficacy becomes more limited, and toxicity accumulates. What we
      have learned in the past decades is that while the targeted therapeutics approach
      may be highly successful in less complex tumors, cancers defined by carcinogen
      induced genomic chaos, such a UV-induced melanoma or tobacco-induced lung cancer,
      are driven by a multitude of competing molecular pathways and, as such, are not
      as successfully managed by a similar approach. Luckily, in the past years, the
      field of cancer immunotherapy has become more fully developed with the emergence
      of checkpoint blockade inhibitor therapy. These promising new agents are
      particularly well suited for tumors with a high mutational burden due to
      underlying genomic disarray. While still in its infancy, we predict that cancer
      immunotherapy will offer a better alternative to our current targeted approach
      and eagerly await the results of several ongoing clinical trials that will
      elucidate this new direction in cancer therapy. 

PMID- 26222083
TI  - Targeting the Tumor Microenvironment to Enhance Pediatric Brain Cancer Treatment.
AB  - Strategies targeting the microenvironment of pediatric brain cancers have the
      potential to improve the efficacy of standard and genome-based molecular
      therapeutics. These strategies also have the potential of helping resolve many of
      the challenges associated with developing new drugs and running clinical trials
      for relatively small pediatric brain tumor population. Disrupting vital paracrine
      and physical interactions between cancer cells and surrounding stroma, targeting
      and normalizing the abnormal tumor vasculature, and/or inducing antitumor
      immunity represent some of the most promising approaches. A comprehensive
      characterization of the pediatric brain tumor microenvironment's composition and
      function and its modulation by chemoradiation and molecularly targeted therapies
      is warranted to develop and effectively implement these approaches. 

PMID- 26222084
TI  - Nanomedicines Targeting the Tumor Microenvironment.
AB  - We review recent progress in cancer nanomedicine to overcome the delivery
      barriers in tumor microenvironment, including the understanding in the
      nanomedicine delivery process, stimulus-responsive delivery, and several new
      strategies to normalize tumor microenvironment. The application of nanomedicine
      in cancer immunotherapy, a renewed cancer therapy by recent breakthrough, is also
      highlighted. 

PMID- 26222082
TI  - Orchestrating the Tumor Microenvironment to Improve Survival for Patients With
      Pancreatic Cancer: Normalization, Not Destruction.
AB  - Pancreatic cancer is the fourth leading cause of cancer death in the United
      States. The microenvironment of pancreatic cancer could be one of the "perfect
      storms" that support the growth of a cancer. Indeed, pancreatic cancer may be the
      poster child of a problem with the microenvironment. In this article, we review
      the rationale and attempts to date on modifying or targeting structural proteins
      in the microenvironment including hyaluronan (HA) (in primary and metastases),
      collagen, and SPARC (secreted protein, acidic, and rich in cysteine). Indeed,
      working in this area has produced a regimen that improves survival for patients
      with advanced pancreatic cancer (nab-paclitaxel + gemcitabine). In addition, in
      initial clinical trials, PEGylated hyaluronidase appears promising. We also
      review a new approach that is different than targeting/destroying the
      microenvironment and that is orchestrating, reengineering, reprogramming, or
      normalizing the microenvironment (including normalizing structural proteins,
      normalizing an immunologically tumor-friendly environment to a less friendly
      environment, reversing epithelial-to-mesenchymal transition, and so on). We
      believe this will be most effectively done by agents that have global effects on
      transcription. There is initial evidence that this can be done by agents such as
      vitamin D derivatives and other new agents. There is no doubt these opportunities
      can now be tried in the clinic with hopefully beneficial effects. 

PMID- 26222085
TI  - Identifying Blood-Based Protein Biomarkers for Antiangiogenic Agents in the
      Clinic: A Decade of Progress.
AB  - Agents that inhibit tumor angiogenesis are widely used and have provided
      meaningful survival benefits to patients in multiple disease settings. However,
      these agents differ significantly in their mechanisms of action and potential
      toxicities, and there are currently no prospectively validated biomarkers to
      guide the selection of agents for individual patients. Blood-based protein
      biomarkers are well suited for trials investigating antiangiogenic agents for
      multiple reasons. Many elements of the molecular pathways that antiangiogenic
      agents target are present and detectable in the circulation, sample collection is
      minimally invasive, and samples can be collected throughout the course of
      treatment. Blood-based biomarkers for antiangiogenic therapies are urgently
      needed to guide the development of therapeutic strategies. This review provides a
      brief summary of the current blood-based protein biomarkers for antiangiogenic
      therapies. 

PMID- 26222086
TI  - Mining the Human Proteome: Biomarker Discovery for Human Cancer and Metastases.
AB  - As our knowledge of the mechanisms underlying cancer development and progression
      has increased, so too have more effective, less toxic, and targeted therapies
      begun to reach the clinic. However, the full impact of these clinical advances
      and the practical success of the emerging field of precision medicine are
      dependent on the discovery and validation of sensitive and accurate biomarkers
      that can enable appropriate and rigorous sample type and patient selection,
      reliable longitudinal monitoring of therapeutic efficacy, and even risk
      assessment and early detection. Within the context of this review, we examine
      state-of-the-art approaches to the discovery and validation of noninvasive cancer
      biomarkers, with a specific emphasis on those that are protein or protein
      associated ones. We also review sample selection strategies, currently utilized
      proteomic approaches for both discovery and validation requirements, and data
      analysis standards. Finally, we provide examples of these elements of biomarker
      discovery and validation from our own biomarker research. 

PMID- 26222087
TI  - Vascular Magnetic Resonance Imaging in Brain Tumors During Antiangiogenic Therapy
      -Are We There Yet?
AB  - Abnormal tumor vasculature is a potent mediator of treatment resistance because
      it results in heterogeneous perfusion, hypoxia, increased interstitial fluid
      pressure, and incomplete penetration of cytotoxic chemotherapies. Targeting this
      abnormal tumor vasculature is a promising therapeutic strategy, but results with
      antiangiogenic drugs in brain cancer have been mixed. Vasculature's response to
      treatment is a dynamic physiological process that can change rapidly throughout
      treatment, so it requires noninvasive techniques to serially monitor these
      changes in order to improve outcome. We review the role of vascular magnetic
      resonance imaging to measure tumor response to treatment and highlight
      opportunities and future avenues for expanding these promising techniques. 

PMID- 26222089
TI  - The Tumor Microenvironment Regulates CD19 and CD20 Immunotherapy for Lymphoma.
AB  - B cells have diverse functions during immune responses, including antibody
      production, antigen presentation, and cytokine secretion. Multiple lymphomas and
      leukemias derive from malignant B cells, so therapies that deplete B cells are
      clinically important, particularly antibodies targeting the B cell-specific
      surface molecules CD19 and CD20. Macrophages are the principal mediators of CD19
      and CD20 monoclonal antibody-dependent B-cell and lymphoma depletion in mice
      through Fcgamma receptor-dependent phagocytosis. Thereby, the extent of CD19 or
      CD20 antibody-induced B cell and tumor depletion in vivo is influenced by
      molecular changes within tumors and genetic variations between individuals. In
      addition to Fcgamma receptor polymorphisms, lymphoma- and regulatory B cell
      derived cytokine production and macrophage localization and function within tumor
      microenvironments influence tumor clearance. Given the dynamic interactions of
      these factors, the identification of effector cell and tumor microenvironment
      genetic alterations will identify molecular targets that enhance immunotherapies
      for the treatment of human diseases. 

PMID- 26222088
TI  - Myeloid Cells as Targets for Therapy in Solid Tumors.
AB  - It is well established that cancer development ensues based on reciprocal
      interactions between genomically altered neoplastic cells and diverse populations
      of recruited "host" cells co-opted to support malignant progression. Among the
      host cells recruited into tumor microenvironments, several subtypes of myeloid
      cells, including macrophages, monocytes, dendritic cells, and granulocytes
      contribute to tumor development by providing tumor-promoting factors as well as a
      spectrum of molecules that suppress cytotoxic activities of T lymphocytes. Based
      on compelling preclinical data revealing that inhibition of critical myeloid
      based programs leads to tumor suppression, novel immune-based therapies and
      approaches are now entering the clinic for evaluation. This review discusses
      mechanisms underlying protumorigenic programming of myeloid cells and discusses
      how targeting of these has potential to attenuate solid tumor progression via the
      induction and of mobilization CD8 cytotoxic T cell immunity. 

PMID- 26222091
TI  - Nursing care of children in general practice settings: roles and
      responsibilities.
AB  - AIMS: To examine roles and responsibilities of Practice Nurses in the area of
      child health and development and in advising parents about child health issues.
      BACKGROUND: As the focus of Australia's health care system shifts further towards
      the primary health care sector, governmental initiatives require that Practice
      Nurses are knowledgeable, confident and competent in providing care in the area
      of child health and development. Little is known about roles and responsibilities
      of Practice Nurses in this area. DESIGN: Cross-sectional survey design. METHODS:
      Practice Nurses completed a national online survey examining the roles and
      responsibilities in child health and development, professional development needs
      and role satisfaction. Data were collected from June 2010-April 2011. RESULTS:
      Respondents (N = 159) reported having a significant role in well and sick child
      care and were interested in extending their role. Frequent activities included
      immunization, phone triage/advice, child health/development advice, wound care
      and Healthy Kids Checks. However, few had paediatric/child nursing backgrounds or
      postgraduate qualifications in paediatric nursing and they reported limited
      preparation for the role. Practice Nurses reported difficulties with keeping up
      to-date with child health information and advising parents confidently.
      Satisfaction was relatively low regarding opportunities and encouragement to
      undertake professional development and expand scope of practice. CONCLUSION:
      Practice Nurses are largely unprepared to meet the demands of their child health
      role and need support to develop and maintain the skills and knowledge base
      necessary for high-quality, evidence-based practice. Both financial and time
      support is needed to enable Practice Nurses to access child health professional
      development.

PMID- 26222090
TI  - alpha7 nicotinic ACh receptor-deficient mice exhibit sustained attention
      impairments that are reversed by beta2 nicotinic ACh receptor activation.
AB  - BACKGROUND AND PURPOSE: Disruptions of executive function, including attentional
      deficits, are a hallmark of a number of diseases. ACh in the prefrontal cortex
      regulates attentive behaviour; however, the role of alpha7 nicotinic ACh receptor
      (alpha7nAChR) in attention is contentious. EXPERIMENTAL APPROACH: In order to
      probe attention, we trained both wild-type and alpha7nAChR knockout mice on a
      touch screen-based five-choice serial reaction time task (5-CSRT). Following
      training procedures, we then tested sustained attention using a probe trial
      experiment. To further differentiate the role of specific nicotinic receptors in
      attention, we then tested the effects of both alpha7nAChR and beta2nAChR agonists
      on the performance of both wild-type and knockout mice on the 5-CSRT task. KEY
      RESULTS: At low doses, alpha7nAChR agonists improved attentional performance of
      wild-type mice, while high doses had deleterious effects on attention.
      alpha7nAChR knockout mice displayed deficits in sustained attention that were not
      ameliorated by alpha7nAChR agonists. However, these deficits were completely
      reversed by the administration of a beta2nAChR agonist. Furthermore,
      administration of a beta2nAChR agonist in alpha7nAChR knockout mice elicited
      similar biochemical response in the prefrontal cortex as the administration of
      alpha7nAChR agonists in wild-type mice. CONCLUSIONS AND IMPLICATIONS: Our
      experiments reveal an intricate relationship between distinct nicotinic receptors
      to regulate attentional performance and provide the basis for targeting
      beta2nAChRs pharmacologically to decrease attentional deficits due to a
      dysfunction in alpha7nAChRs.

PMID- 26222092
TI  - Safely Increase the Minimally Invasive Hysterectomy Rate: A Novel Three-Tiered
      Preoperative Categorization System Can Predict the Difficulty for Benign Disease.
AB  - CONTEXT: A nonlaparotomic route is recommended for hysterectomy for benign
      indications. OBJECTIVE: 1) Predict the difficulty of hysterectomy to treat benign
      disease as measured by operative time and risk of laparotomy, 2) confirm the
      safety and quality of increasing our minimally invasive hysterectomy (MIH) rate,
      and 3) determine whether the assistant's experience affected the likelihood of an
      MIH being performed in equally difficult hysterectomies. DESIGN: All
      hysterectomies for benign disease performed at the Kaiser Permanente Fontana
      Medical Center in Fontana, CA, in 2012 were reviewed for length of surgery,
      length of stay, complications, and readmissions. A three-tiered category system
      was developed from four preoperative parameters (body mass index, number of
      vaginal deliveries, clinical uterine size, and history of major abdominal
      surgery) to anticipate length and difficulty of surgery. MAIN OUTCOME MEASURES:
      Rates of MIH, complications, and readmissions as well as length of surgery and
      length of stay for similarly difficult hysterectomies. These outcomes were
      compared with surgeons' and assistants' experience. RESULTS: Of 576
      hysterectomies performed for benign disease, 89% were MIH with a 3% complication
      rate and 4% readmission rate. An increase in the hysterectomy category was
      statistically significantly associated with longer surgery times and a higher
      percentage of laparotomy. With the most experienced assistants, the MIH rate was
      98%. CONCLUSIONS: Using 4 preoperative parameters, the average operating time for
      hysterectomy for benign disease can be predicted. A higher hysterectomy category
      predicts a more difficult surgery. Our center has increased its MIH rate to 89%
      while maintaining safety.

PMID- 26222093
TI  - Effect of Structured Touch and Guided Imagery for Pain and Anxiety in Elective
      Joint Replacement Patients--A Randomized Controlled Trial: M-TIJRP.
AB  - CONTEXT: Postoperative management of pain after total joint arthroplasty remains
      a challenge despite advancements in analgesics. Evidence shows that complementary
      modalities with mind-body and tactile-based approaches are valid and effective
      adjuncts to reduce pain and anxiety postoperatively. OBJECTIVE: To investigate
      the effectiveness of the "M" Technique (M), a registered method of structured
      touch using a set sequence and number of strokes, and a consistent level of
      pressure on hands and feet, compared with guided imagery and usual care, for the
      reduction of pain and anxiety in patients undergoing elective total knee or hip
      replacement surgery. METHODS: Randomized controlled trial: M-TIJRP (MiTechnique
      and guided Imagery in Joint Replacement Patients [Mighty Junior P]). At a
      community hospital, 225 male and female patients, aged 38 to 90 years, undergoing
      elective total hip or knee replacement were randomly assigned to 1 of 3 groups
      (75 patients in each): M, guided imagery, or usual care. They were blinded to
      their assignment until the intervention. MAIN OUTCOME MEASURES: Reduction of pain
      and anxiety postoperatively. Secondary outcomes measured use of pain medication
      and patient satisfaction. RESULTS: This study yielded positive findings for the
      management of pain and anxiety in patients undergoing elective joint replacement
      using M and guided imagery for 18 to 20 minutes compared with usual care. M
      showed the largest predicted decreases in both pain and anxiety between groups.
      There was no significant difference in narcotic pain medication use between
      groups. Patient satisfaction survey ratings were highest for M, followed by
      guided imagery. CONCLUSION: The benefit of M may be because of the specifically
      structured sequence of touch by competent caring, trained providers.

PMID- 26222094
TI  - Primary Health Care and Narrative Medicine.
AB  - Primary health care has received a lot of attention since the Alma Ata
      Conference, convened by the World Health Organization in 1978. Key to the
      strategy to improve health care outlined at the Alma Ata conference is citizen
      participation in every phase of service delivery. Although the goals of primary
      health care have not been achieved, the addition of narrative medicine may
      facilitate these ends. But a new epistemology is necessary, one that is
      compatible with narrative medicine, so that local knowledge is elevated in
      importance and incorporated into the planning, implementation, and evaluation of
      health programs. In this way, relevant, sustainable, and affordable care can be
      provided. The aim of this article is to discuss how primary health care might be
      improved through the introduction of narrative medicine into planning primary
      health care delivery.

PMID- 26222095
TI  - Long-Term (3 Year) Effects of a Single Thermal Pulsation System Treatment on
      Meibomian Gland Function and Dry Eye Symptoms.
AB  - PURPOSE: The present study examined the long-term (3 years) effects of a single
      (12 min) thermal pulsation system (TPS) treatment on symptomatic patients with
      evaporative dry eye disease (DED) secondary to meibomian gland dysfunction (MGD).
      METHODS: In this prospective, cohort, observational, single-center study design,
      signs (meibomian gland secretion [MGS] scores and tear film breakup time [TBUT])
      and symptoms (Ocular Surface Disease Index [OSDI] and Standard Patient Evaluation
      of Eye Dryness [SPEED] questionnaires) were determined in 20 patients (40 eyes)
      with MGD and dry eye symptoms at baseline (BL), 1 month, and 3 years post-TPS
      treatment using LipiFlow. RESULTS: Meibomian gland secretion scores increased
      from BL (4.5+/-0.8) to 1 month (12.0+/-1.1, P<=0.001). Improvement persisted at 3
      years (18.4+/-1.4) relative to BL (P<=0.001). Meibomian gland secretion scores in
      all regions of the lower eyelid were improved over BL at 1 month (nasal
      [P<=0.001], central [P<=0.001], temporal [P<=0.01]) and 3 years (nasal
      [P<=0.001], central [P<=0.001], temporal [P<=0.001]). TBUT increased from BL
      (4.1+/-0.4) to 1 month (7.9+/-1.4, P<=0.05) but was not significantly different
      than BL at 3 years (4.5+/-0.6, P>0.05). The OSDI scores decreased from BL (26.0+/
      4.6) to 1 month (14.7+/-4.3, P<=0.001) but returned to BL levels at 3 years
      (22.5+/-5.4, P>0.05). The SPEED scores decreased from BL (13.4+/-1.0) to 1 month
      (6.5+/-1.3, P<=0.001), and this improvement persisted at 3 years (9.5+/-1.6,
      P<=0.001). CONCLUSIONS: Thermal pulsation may be a uniquely efficacious treatment
      option for DED secondary to MGD in that a single 12-min procedure is associated
      with significant improvement in MGS and SPEED scores for up to 3 years.

PMID- 26222096
TI  - Effects of Glaucoma Tube Surgery on Corneal Endothelial Cells: A Review.
AB  - The etiology of corneal decompensation after aqueous shunt implantation remains
      poorly understood. With the use of anterior segment optical coherence tomography
      and specular microscopy, the relationship of these implants to the surrounding
      tissues can be investigated over time. This article will review the current
      knowledge pertaining to endothelial cell loss related to glaucoma and surgery and
      highlight possible causes that have been proposed for endothelial cell loss after
      aqueous shunt implantation. 

PMID- 26222097
TI  - Epidemiology and Outcomes of Kocuria Keratitis.
AB  - OBJECTIVE: To determine the characteristics of infectious keratitis caused by
      Kocuria spp. METHODS: Retrospective case series. Information included demographic
      data, medical history, risk factors associated with infectious keratitis,
      clinical characteristics, microbiological results and drug sensitivity, clinical
      course, management, and visual outcomes. RESULTS: Eight patients were included (7
      females and 1 male; mean age, 66.2 years; age range, 42-84 years). All patients
      presented risk factors for infectious complications, such as filamentous
      keratitis, dry eye, blepharitis, and persistent corneal edema. In all cases,
      ulcers were classified as severe. The infection resolved with medical treatment
      in one eye only. One case was treated with amniotic membrane graft. Two patients
      required keratoplasty (lamellar and penetrating), and one case needed
      sclerokeratoplasty. In three cases, the keratitis was severe enough to require
      evisceration. The final visual acuity ranged from 20/25 to no light perception.
      CONCLUSIONS: Bacterial keratitis by Kocuria spp. is a rare infection that may
      have an unexpected clinical course and possible serious outcomes. This pathogen
      should be considered in patients with unusual clinical course. Local or systemic
      immune compromise in the genesis of the disease must also be taken into account,
      and ophthalmologists should be more suspicious in this vulnerable group of
      patients.

PMID- 26222098
TI  - Sterile Corneal Infiltrates Secondary to Psoriasis Exacerbations: Topical
      Tacrolimus as an Alternative Treatment Option.
AB  - INTRODUCTION: Psoriasis is a common chronic inflammatory skin disease. Ocular
      manifestations, which occur in 10% to 20% of cases of psoriasis, are usually
      bilateral and often present during an exacerbation of the psoriasis. Serious
      corneal involvement is rare but can be devastating. CASE REPORT: Two cases of
      sterile corneal infiltrates secondary to an exacerbation of psoriasis are
      presented. Treatment involved the use of 0.02% topical tacrolimus ointment, which
      resulted in resolution of the symptoms and infiltrates. DISCUSSION AND
      CONCLUSION: Topical tacrolimus may be considered as an alternative treatment
      option to corticosteroids in sterile corneal infiltrates.

PMID- 26222099
TI  - School-level economic disadvantage and obesity in middle school children in
      central Texas, USA: a cross-sectional study.
AB  - BACKGROUND: Although children of lower socio-economic status (SES) in the United
      States have generally been found to be at greater risk for obesity, the SES
      obesity association varies when stratified by racial/ethnic groups-with no
      consistent association found for African American and Hispanic children. Research
      on contextual and setting-related factors may provide further insights into
      ethnic and SES disparities in obesity. We examined whether obesity levels among
      central Texas 8th grade students (n=2682) vary by school-level economic
      disadvantage across individual-level family SES and racial/ethnicity groups. As a
      secondary aim, we compared the association of school-level economic disadvantage
      and obesity by language spoken with parents (English or Spanish) among Hispanic
      students. METHODS: Multilevel regression models stratified by family SES and
      ethnicity were run using cross-sectional baseline data from five school districts
      participating in the Central Texas CATCH Middle School project. For family SES,
      independent multi-level logistic regression models were run for total sample and
      by gender for each family SES stratum (poor/near poor/just getting by, living
      comfortably, and very well off), adjusting for age, ethnicity, and gender.
      Similarly, multi-level regression models were run by race/ethnic group (African
      American, Hispanic, and White), adjusting for age, family SES, and gender.
      RESULTS: Students attending highly economically disadvantaged (ED) schools were
      between 1.7 (95% CI: 1.1-2.6) and 2.4 (95% CI: 1.2-4.8) times more likely to be
      obese as students attending low ED schools across family SES groups (p<.05).
      African American (OR(Adj) =3.4, 95% CI: 1.1-11.4), Hispanic (OR(Adj)=1.8, 95% CI
      1.1-3.0) and White (OR(Adj)=3.8, 95% CI: 1.6-8.9) students attending high ED
      schools were more likely to be obese as counterparts at low ED schools (p<.05).
      Gender-stratified findings were similar to findings for total sample, although
      fewer results reached significance. While no obesity differences across school ED
      categories were found for Hispanic Spanish-speaking students, Hispanic English
      speaking students (HES) attending high ED schools were 2.4 times more likely to
      be obese as HES students at low ED schools (p=.003). CONCLUSION: Findings support
      the need to prioritize economically disadvantaged schools for obesity prevention
      efforts and support further exploration of school SES context in shaping
      children's physical activity and dietary behaviors.

PMID- 26222100
TI  - Expressions of matrix metalloproteinases-1 and -9 and opioid growth factor in
      rabbit cornea after lamellar keratectomy and treatment with 1% nalbuphine.
AB  - PURPOSES: To evaluate the effects of nalbuphine 1% on the expression of
      metalloproteinase 1 (MMP-1), metalloproteinase 9 (MMP-9), and opioid growth
      factor (OGF) in rabbit corneas after lamellar keratectomy. METHODS: The rabbits
      were assigned to two groups: group nalbuphine (GN, n=30), which received 30 uL of
      nalbuphine 1% in 4 daily applications at regular intervals until corneal
      epithelialization, and group control (GC, n=30), which received physiological
      saline solution under the same conditions adopted in GN. The corneas were
      collected for immunohistochemistry on days 1, 3, 5, 7, and 9 after lamellar
      keratectomy, and the expressions of MMP-1, MMP-9, and OGF were analyzed. RESULTS:
      The expressions of MMP-1 and MMP-9 increased until day 5 of the evaluation, with
      no differences observed between GN and GC (p>0.05). On days 7 and 9, significant
      reductions were observed in the expression of MMP-1 (p<0.01), with no differences
      observed between GN and GC (p>0.05). The expression of OGF was constant in all
      periods (p>0.05), restricted to the corneal epithelium, and there was no
      difference between the groups (p>0.05). CONCLUSIONS: The study results showed
      that nalbuphine 1% did not alter the expression patterns of MMP-1, MMP-9, and OGF
      in rabbit corneas after lamellar keratectomy.

PMID- 26222101
TI  - The relationship of birth weight, gestational age, and postmenstrual age with
      ocular biometry parameters in premature infants.
AB  - PURPOSE: To analyze ocular biometry parameters and evaluate their relationship
      with gestational age, birth weight, and postmenstrual age in prematurely born
      infants. METHODS: The right eyes of 361 premature infants born before the 36th
      gestational week were evaluated. Birth weight, gestational week, and gender were
      recorded. An A-scan Biometer was used for obtaining axial measurements, including
      anterior chamber depth, lens thickness, vitreous length, and total axial length.
      RESULTS: Gestational age and birth weight values ranged from 23 to 36 weeks and
      from 560 to 2,670 g, respectively. The mean gestational age and birth weight were
      30.8 +/- 2.8 weeks and 1,497.9 +/- 483.6 g, respectively. During the first
      examination (4-5 weeks of postnatal age), birth weight and gestational age of the
      infants correlated significantly and positively with lens thickness, vitreous
      length, and axial length (r>0.5, p<0.001), but not with anterior chamber depth
      (r<0.5). Increased vitreous and axial lengths correlated significantly with
      increasing postmenstrual age of the infants (r=0.669, p<0.001; r=0.845, p<0.001,
      respectively). CONCLUSIONS: Lens thickness, vitreous length, and axial length,
      but not anterior chamber depth, were significantly correlated with birth weight
      and gestational age. All four parameters increased with increasing postmenstrual
      age, with higher correlations for vitreous and axial lengths than for anterior
      chamber depth and lens thickness. It was concluded that axial elongation resulted
      primarily from increasing posterior chamber length.

PMID- 26222102
TI  - Evaluation of possible factors affecting contrast sensitivity function in
      patients with primary Sjogren's syndrome.
AB  - PURPOSE: The contrast sensitivity (CS) function in patients with primary
      Sjogren's syndrome (pSS) may be impaired either frequently as a result of dry eye
      diseases or rarely as a result of optic neuropathy. In this study, we aimed to
      evaluate the CS function in pSS patients as well as to assess corneal aberrations
      and thickness of the peripapillary retinal nerve fiber layer (pRNFL). METHODS:
      Fourteen eyes of 14 pSS patients (pSS group) and 14 eyes of 14 healthy
      participants (control group) were subjected to assessment of CS at the spatial
      frequencies of 1.5, 3.0, 6.0, 12, and 18 cycles/degree (cpd) using a functional
      visual acuity contrast test (FACT); measurement of corneal high-order aberrations
      (HOAs) in terms of coma-like, spherical-like, and total HOAs using Scheimpflug
      corneal topography; and measurement of the thickness of both the macular ganglion
      cell-inner plexiform layer (mGCIPL) and pRNFL in all quadrants using optical
      coherence tomography. None of the participants were under treatment with
      artificial tears. RESULTS: The results of the CS test did not differ between the
      2 groups at all spatial frequencies (p>0.05). In addition, there were no
      statistically significant differences between the 2 groups in terms of corneal
      HOAs (p>0.05) and thickness of mGCIPL (p>0.05). However, among all quadrants,
      only the inferior quadrant of pRNFL in pSS patients was statistically
      significantly thinner than that in the healthy participants (p=0.04).
      CONCLUSIONS: The CS function in pSS patients can be maintained with normal
      thickness of both pRNFL and mGCIPL and with lack of increased corneal HOAs, which
      may be present even in the absence of artificial tear usage.

PMID- 26222103
TI  - Intraocular lens explantation or exchange: indications, postoperative
      interventions, and outcomes.
AB  - PURPOSE: To analyze the indications for explantation or exchange of intraocular
      lenses (IOLs), which were originally implanted for the correction of aphakia
      during cataract extraction. METHODS: All cases that involved intraocular lens
      explantation or exchange in one institution between January 2008 and December
      2014 were analyzed retrospectively. RESULTS: In total, 93 eyes of 93 patients
      were analyzed. The median time interval between implantation and explantation of
      the anterior chamber intraocular lenses (AC IOL) and posterior chamber
      intraocular lenses (PC IOL) was 83.40 +/- 83.14 months (range: 1-276 months) and
      55.14 +/- 39.25 months (range: 1-168 months), respectively. Pseudophakic bullous
      keratopathy (17 eyes, 38.6%) and persistent iritis (12 eyes, 27.8%) in the AC IOL
      group and dislocation or decentration (30 eyes, 61.2%) and incorrect IOL power
      (nine eyes, 18.4%) in the PC IOL group were the most common indications for
      explantation of IOLs. The mean logMAR best corrected visual acuity (BCVA)
      improved significantly from 1.30 preoperatively to 0.62 postoperatively in the PC
      IOL group (p<0.001) but did not improve significantly in the AC IOL group
      (p=0.186). CONCLUSIONS: The primary indication for IOL explantation or exchange
      was pseudophakic bullous keratopathy in the AC IOL group and was dislocation or
      decentration in the PC IOL group. PC IOL explantation or exchange is safe and
      improves visual acuity.

PMID- 26222104
TI  - Insulin replacement restores the vesicular secretory apparatus in the diabetic
      rat lacrimal gland.
AB  - PURPOSE: In the lacrimal gland (LG) acinar cells, signaling regulates the release
      of secretory vesicles through specific Rab and SNARE exocytotic proteins. In
      diabetes mellitus (DM), the LGs are dysfunctional. The aim of this work was to
      determine if secretory apparatus changes were associated with any effects on the
      secretory vesicles (SV) in diabetic rats as well as the expression levels of
      constituent Rab and members of the SNARE family, and if insulin supplementation
      reversed those changes. METHODS: DM was induced in male Wistar rats with an
      intravenous dose of streptozotocin (60 mg/kg). One of the two diabetic groups was
      then treated every other day with insulin (1 IU). A third control group was
      injected with vehicle. After 10 weeks, Western blotting and RT-PCR were used to
      compared the Rab and SNARE secretory factor levels in the LGs. Transmission
      electron microscopy evaluated acinar cell SV density and integrity. RESULTS: In
      the diabetes mellitus group, there were fewer and enlarged SV. The Rab 27b, Rab
      3d, and syntaxin-1 protein expression declined in the rats with diabetes
      mellitus. Insulin treatment restored the SV density and the Rab 27b and syntaxin
      expression to their control protein levels, whereas the Vamp 2 mRNA expression
      increased above the control levels. CONCLUSIONS: Diabetes mellitus LG changes
      were associated with the declines in protein expression levels that were involved
      in supporting exocytosis and vesicular formation. They were partially reversed by
      insulin replacement therapy. These findings may help to improve therapeutic
      management of dry eye in diabetes mellitus.

PMID- 26222105
TI  - Diode laser-assisted transcanalicular dacryocystorhinostomy: the effect of age on
      the results.
AB  - PURPOSE: The aim of this study was to explore the effect of age on the success of
      transcanalicular diode laser-assisted dacryocystorhinostomy (TCDCR). METHODS:
      Seventy patients (70 eyes) who underwent transcanalicular diode laser-assisted
      dacryocystorhinostomy for the treatment of nasolacrimal duct obstruction as a
      primary surgery were included in this retrospective, nonrandomized study. The
      patients were divided into two groups according to age. Mean ages were 21.3 +/-
      3.3 in group 1 and 60.3 +/- 7.3 in group 2. The records of the 3-, 6-, and 12
      month follow-up examinations were evaluated, and the anatomical and functional
      outcomes were noted. Functional success was defined as the absence of epiphora as
      indicated by the patient. Anatomical success was determined as patency of the neo
      ostium with irrigation. RESULTS: At the 3-month follow-up, 67% cases in group 1
      showed anatomical success and 52% showed functional success; in group 2, the
      rates were 100% and 92%, respectively. Functional and anatomical success rates
      were the same for both the 6- and 12-month visits; 46% in group 1 and 76% in
      group 2. The results in group 2 were significantly better at all three follow-up
      visits (p<0.05). CONCLUSIONS: This study clearly showed that the older patients
      experienced better transcanalicular diode laser-assisted dacryocystorhinostomy
      results than the younger patients. The diminished inflammatory response in the
      older population may be a possible contributing factor to these results.

PMID- 26222106
TI  - Anatomical and visual outcomes of ranibizumab injections in retinal pigment
      epithelium tears.
AB  - PURPOSE: To report the anatomical and visual results in patients diagnosed as
      having retinal pigment epithelium (RPE) tears after receiving ranibizumab
      injections. METHODS: Eyes diagnosed as having RPE tears with a minimum 6-month
      follow-up were retrospectively evaluated. Each eye was treated with at least
      three doses of ranibizumab at monthly intervals. Best-corrected visual acuity
      (BCVA), anterior segment findings, intraocular pressure, and fundus examination
      results were evaluated during control visits. Color fundus photography, fundus
      fluorescein angiographies, fundus autofluorescence, and spectral domain optical
      coherence tomography (SD-OCT) images were obtained. The height of pigment
      epithelial detachment (PED) was measured by SD-OCT. RESULTS: Twelve eyes with RPE
      tears were studied. Nine eyes (75%) developed RPE tears during ranibizumab
      injections for choroidal neovascularization (eight eyes with vascularized PED and
      one eye with choroidal osteoma), and tears occurred in three eyes before any
      injections. The median number of ranibizumab injections after diagnosis of RPE
      tears was 3 (min 2, max 5). In the most recent follow-up visit, there was no
      statistically significant correlation between the grade of RPE and logMAR of BCVA
      (p>0.05, r=0.112). Eight of twelve eyes had PED, and seven of these had irregular
      PED contours before injection therapy. The mean PED height was 447 +/- 122 um.
      CONCLUSIONS: In this series, RPE tears developed mostly after intravitreal anti
      VEGF injections for vascularized PED. Increased vertical height and irregular
      contours of the PEDs can be risk factors for the formation of RPE tears. The
      continuation of anti-VEGF therapy after tear formation is beneficial for vision
      improvement in eyes with RPE tears.

PMID- 26222107
TI  - Safety of warfarin therapy during cataract surgery under topical anesthesia.
AB  - PURPOSE: To analyze the safety of warfarin therapy during cataract surgery under
      topical anesthesia. METHODS: This was a prospective nonrandomized comparative
      study of 60 eyes of 60 patients treated with or without concurrent oral warfarin
      anticoagulant therapy, referred for cataract surgery under topical anesthesia.
      The sample included a treatment (n=30) and a control (n=30) group. RESULTS: There
      were no records of intraoperative or postoperative intracameral bleeding
      complications in both the groups. At 1-month postoperative follow-up, 90.0% of
      patients presented spectacle-corrected visual acuity of at least 20/40.
      CONCLUSION: Cataract surgery by phacoemulsification with topical anesthesia can
      be successfully conducted without discontinuing warfarin.

PMID- 26222108
TI  - Factors affecting visual loss and visual recovery in patients with pseudotumor
      cerebri syndrome.
AB  - PURPOSE: To investigate the frequency of visual loss (VL), possible predictive
      factors of VL, and improvement in patients with pseudotumor cerebri (PTC)
      syndrome. METHODS: We reviewed 50 PTC patients (43 females, seven males) who
      underwent neuro-ophthalmic examination at the time of diagnosis and after
      treatment. Demographic data, body mass index (BMI), time from symptom onset to
      diagnosis (TD), maximum intracranial pressure (MIP), occurrence of cerebral
      venous thrombosis (CVT), and treatment modalities were reviewed. VL was graded as
      mild, moderate, or severe on the basis of visual acuity and fields. Predictive
      factors for VL and improvement were assessed by regression analysis. RESULTS: The
      mean +/- SD age, BMI, and MIP were 35.2 +/- 12.7 years, 32.0 +/- 7.5 kg/cm2, and
      41.9 +/- 14.5 cmH2O, respectively. Visual symptoms and CVT were present in 46 and
      eight patients, respectively. TD (in months) was <1 in 21, 1-6 in 15, and >6 in
      14 patients. Patients received medical treatment with (n=20) or without (n=30)
      surgery. At presentation, VL was mild in 16, moderate in 12, and severe in 22
      patients. Twenty-eight patients improved and five worsened. MIP, TD, and
      hypertension showed a significant correlation with severe VL. The best predictive
      factor for severe VL was TD >6 months (p=0.04; odds ratio, 5.18). TD between 1
      and 6 months was the only factor significantly associated with visual improvement
      (p=0.042). CONCLUSIONS: VL is common in PTC, and when severe, it is associated
      with a delay in diagnosis. It is frequently permanent; however, improvement may
      occur, particularly when diagnosed within 6 months of symptom onset.

PMID- 26222110
TI  - Visual loss resulting from immunosuppressive therapy in patients with syphilitic
      uveitis.
AB  - Permanent visual loss can be caused by improper use of immunosuppressive therapy
      in cases of uveitis without differential diagnosis of syphilitic uveitis. We
      present four cases of syphilitic uveitis that were incorrectly diagnosed as being
      secondary to rheumatic diseases and were subsequently treated with
      immunosuppressive therapy, leading to permanent visual loss. These cases
      highlight the importance of ruling out syphilis in the differential diagnosis of
      inflammatory ocular diseases before starting use of immunosuppressive therapy.

PMID- 26222109
TI  - Refraction and eye anterior segment parameters in schizophrenic patients.
AB  - PURPOSE: To evaluate the difference in terms of refractive errors and anterior
      segment parameters between schizophrenic patients and healthy volunteers.
      METHODS: This study compared 70 patients (48 men) who were diagnosed with
      schizophrenia with a control group of 60 (35 men) who were similar in terms of
      age, gender, education, and socioeconomic level. Anterior segment examination was
      performed using a Scheimflug system. Axial length and lens thickness (LT) were
      measured using optic biometry. The following tests were administered to the
      psychiatric patient group: Brief Psychiatric Rating Scale (BPRS), Scale for the
      Assessment of Negative Symptoms (SANS), and Scale for the Assessment of Positive
      Symptoms (SAPS). RESULTS: Mild myopia was detected in both the schizophrenic and
      control groups, with no statistically significant difference (p>0.005). Corneal
      volume (CV), anterior chamber volume (ACV), anterior chamber depth (ACD), and
      central corneal thickness (CCT) values were lower in the schizophrenic group, and
      there was a statistically significant between-group difference (p=0.026, p=0.014,
      p=0.048, and p=0.005, respectively). LT was greater in schizophrenics, and the
      difference was found to be statistically significant (p=0.006). A statistically
      significant negative correlation was found between SAPS and cylinder values
      (p=0.008). The axial eye length, cylinder value, pupil diameter, mean
      keratometric value, and anterior chamber angle revealed no statistically
      significant difference between the groups (p>0.05). CONCLUSION: No statistically
      significant difference was detected in terms of refraction disorders between
      schizophrenics and the healthy control group, while some differences in anterior
      chamber parameters were present. These results demonstrate that schizophrenics
      may exhibit clinical and structural differences in the eye.

PMID- 26222111
TI  - Idiopathic polypoidal choroidal vasculopathy masquerading as choroidal tumors:
      one year follow-up of a peripheral lesion.
AB  - This case report describes peripheral idiopathic polypoidal choroidal
      vasculopathy (IPCV) with a collection of small aneurysmal dilations that
      masqueraded as choroidal tumors in an elderly patient. A 68-year-old African
      American woman was referred to us with a suspected diagnosis of asymptomatic
      vascular choroidal tumor and choroidal capillary hemangioma, affecting the
      temporal peripheral fundus. Upon examination, optical coherence tomography (OCT)
      revealed two large hemorrhagic pigment epithelium detachments (PED), and
      indocyanine green angiography (ICG) confirmed the diagnosis of IPCV. One year
      later, there was reduction in the hemorrhagic pigment epithelium detachments and
      the lesion took on a different appearance, resembling a choroidal osteoma. No
      treatment was necessary despite the presence of multiple polyps. IPCV is a rare
      condition that can resemble other choroidal diseases depending on the stage of
      presentation. OCT is the best tool to determine the characteristics of the
      lesions, and indocyanine green angiography should be used to confirm the
      diagnosis. Not all cases require treatment. 

PMID- 26222112
TI  - Treatment of cystoid macular edema secondary to chronic non-infectious
      intermediate uveitis with an intraocular dexamethasone implant.
AB  - PURPOSE: To evaluate the use of a slow-release dexamethasone 0.7-mg intravitreal
      implant for cystoid macular edema (CME) secondary to intermediate uveitis and
      refractory to systemic steroids. METHODS: A retrospective study of the best
      corrected visual acuity (BCVA), intraocular inflammation, intraocular pressure
      (IOP), fundus photography, optical coherence tomography (OCT), inflammation, and
      adverse reactions of five patients (women, mean age of 35 years) with cystoid
      macular edema treated with a dexamethasone implant. Patients were evaluated in
      seven visits until the 150th day after the implant. RESULTS: Four patients had
      bilateral pars planitis and one had bilateral intermediate uveitis associated
      with juvenile idiopathic arthritis. Six dexamethasone devices were implanted,
      under topical anesthesia (one each in six eyes, five patients). The mean follow
      up time was 5 months. The best-corrected visual acuity improved in all eyes that
      received an implant, with five having improvements of two or more lines. Optical
      coherence tomography showed thinning of the macula in all eyes treated, and we
      saw a correlation between the best-corrected visual acuity and retinal thinning.
      No serious adverse events occurred and no significant increase in intraocular
      pressure was observed. CONCLUSIONS: Slow-release dexamethasone intravitreal
      implants can effectively treat CME secondary to intermediate uveitis and
      refractory to systemic steroids.

PMID- 26222113
TI  - Safety and feasibility of the use of a bevacizumab-methylcellulose mixture as an
      adjunct to glaucoma surgery: a pilot study.
AB  - Bevacizumab, a monoclonal anti-vascular endothelial growth factor antibody, has
      been suggested as a potential healing therapeutic following glaucoma surgery.
      Here, we aimed to improve the bioavailability of bevacizumab when used as an
      adjunct therapy to non-penetrating deep sclerectomy (DS) by using a bevacizumab
      methylcellulose mixture (BMM). Ten previously non-operated eyes in ten patients
      diagnosed with primary open angle glaucoma underwent DS with a subconjunctival
      injection of 0.3 ml of BMM (bevacizumab 3.75 mg incorporated into 4%
      methylcellulose) at the surgical site. Bevacizumab release was evaluated in vitro
      using size-exclusion high performance liquid chromatography (HPLC). Intraocular
      pressure (IOP), bleb morphology, corneal endothelial cell count (CECC), and
      complications were evaluated at 6 months after surgery. Using HPLC, bevacizumab
      was detected in BMM for up to 72 h. Moreover, all surgical blebs remained
      expanded with hyaline material during the first week. A significant IOP reduction
      (mean +/- SD= -10.3 +/- 5.4 mmHg, P<0.001) and diffuse blebs were observed at the
      final follow-up period. Although CECC was slightly reduced (-7.4%), no
      complications were observed. In conclusion, bevacizumab was released from BMM,
      and the use of this innovative mixture yielded good results following DS with no
      complications. Further studies are required to determine its efficacy prior to
      establishing BMM as an adjunct treatment for penetrating and non-penetrating
      glaucoma surgeries. 

PMID- 26222114
TI  - Association between visual impairment and depression in the elderly: a systematic
      review.
AB  - A systematic review was conducted to investigate the relationship between visual
      impairment and depression in the elderly. We searched electronic databases
      (LILACS, SciELO, MEDLINE, and Cochrane Central Register of Controlled Trials)
      from inception to August 2014 and researched the described references. The search
      strategy used the following terms: (visual impairment or blindness) and (elderly)
      and (depression). Of the 641 electronics, 42 works were selected in full and
      another 20 were identified as being possibly relevant. Ten studies were included.
      The studies ranged in sample size from 31 to 21,995 participants. Depression was
      associated with visual impairment in all studies; however, without
      standardization of diagnostic tests, we could not conduct a meta-analysis or
      establish a relationship between visual impairment and depression in the elderly.

PMID- 26222115
TI  - A review of "approach of Turkish ophthalmologists to micronutrition in age
      related macular degeneration".

PMID- 26222116
TI  - Can glaucoma affect sleep quality?

PMID- 26222126
TI  - Effect of TAK-085 on Low-density Lipoprotein Particle Size in Patients with
      Hypertriglyceridemia: A Double-blind Randomized Clinical Study.
AB  - BACKGROUND: Low-density lipoproteins (LDLs) comprise a heterogeneous group of
      particles with various size and density. A shift to larger LDL particle size is
      mainly the result of a decrease in small dense LDL (sd-LDL) levels and an
      increase in large buoyant LDL (lb-LDL) levels. METHODS: In a randomized, double
      blind study of TAK-085 (containing docosahexaenoic and eicosapentaenoic acid
      ethyl esters [EPA-E]) and an EPA-E product in Japanese patients with
      hypertriglyceridemia, exploratory evaluations of the effects of the LDL particle
      size were performed on the basis of LDL-cholesterol/apolipoprotein B ratios and
      LDL subfractions, which were analyzed with a polyacrylamide gel electrophoresis
      system. RESULTS: Patients were randomized to 12-week treatment with TAK-085 4
      g/day (N = 210), TAK-085 2 g/day (N = 205), or EPA-E 1.8 g/day (N = 195).
      Treatment with TAK-085 4 g/day, TAK-085 2 g/day, and EPA-E 1.8 g/day caused an
      increase in the LDL cholesterol/apolipoprotein B ratios (3.99%, 3.35%, and 0.66%,
      respectively), the mean diameter of LDL particles (1.12%, 0.84%, and 0.67%,
      respectively), and the level of lb-LDL at the end of the study (16.37%, 9.51%,
      and 7.31%, respectively). The increases in the LDL cholesterol/apolipoprotein B
      ratios and the mean diameter of LDL particles from baseline to the end of the
      study were greater with TAK-085 4 g/day than EPA-E 1.8 g/day. TAK-085 4 g/day and
      TAK-085 2 g/day caused a decrease in the sd-LDL levels (-16.21% and -6.96%,
      respectively). CONCLUSION: TAK-085 produced a favorable shift in the LDL particle
      size in Japanese patients with hypertriglyceridemia. JAPIC Clinical Trials
      Information: Japic CTI-090937.

PMID- 26222127
TI  - Attention allocation in social anxiety during a speech.
AB  - Cognitive models assume that social anxiety is associated with and maintained by
      biased information processing, leading to change in attention allocation, which
      can be measured by examining eye movement. However, little is known about the
      distribution of attention among positive, neutral and negative stimuli during a
      social task and the relative importance of positive versus negative biases in
      social anxiety. In this study, eye movement, subjective state anxiety and
      psychophysiology of individuals with high trait social anxiety (HSA) and low
      trait social anxiety (LSA) were measured during a speech task with a pre-recorded
      audience. The HSA group showed longer total fixation on negative stimuli and
      shorter total fixation on positive stimuli compared to the LSA group. We observed
      that the LSA group shifted attention away from negative stimuli, whereas the HSA
      group showed no differential attention allocation. The total duration of fixation
      on negative stimuli predicted subjective anxiety ratings. These results point to
      a negative bias as well as a lack of a positive bias in HSA individuals during
      social threat.

PMID- 26222128
TI  - Microfabrication of Photo-Cross-Linked Hyaluronan Hydrogels by Single- and Two
      Photon Tyramine Oxidation.
AB  - Photo-cross-linking of tyramine-substituted hyaluronan (HA-Tyr) hydrogels is
      demonstrated for the first time. HA-Tyr hydrogels are fabricated via a rapid
      photosensitized process using visible light illumination. Nontoxic conditions
      offer photoencapsulation of human mesenchymal stromal cells (hMSCs) with high
      viability. Macroscopic gels can be formed in less than 10 s, and one- and two
      photon photopatterning enable 2D and 3D microfabrication. Different degrees of
      cross-linking induce different swelling/shrinking, allowing for light-induced
      microactuation. These new tools are complementary to the previously reported
      horseradish peroxidase/hydrogen peroxide cross-linking and allow sequential cross
      linking of HA-Tyr matrices. 

PMID- 26222129
TI  - Education for contraceptive use by women after childbirth.
AB  - BACKGROUND: Contraceptive education is generally a standard component of
      postpartum care, although the effectiveness is seldom examined. The assumptions
      that form the basis of such programs include postpartum women being motivated to
      use contraception and that they will not return to a health provider for family
      planning advice. Women may wish to discuss contraception both prenatally and
      after hospital discharge. Nonetheless, two-thirds of postpartum women have unmet
      needs for contraception. In the USA, many adolescents have repeat pregnancies
      within a year of giving birth. OBJECTIVES: Assess the effectiveness of
      educational interventions for postpartum women on contraceptive use SEARCH
      METHODS: We searched for trials through June 2015 in PubMed, CENTRAL, CINAHL,
      POPLINE, and Web of Science. For current trials, we searched ClinicalTrials.gov
      and ICTRP. Previous searches also included EMBASE and PsycInfo. We also examined
      reference lists of relevant articles. For earlier versions, we contacted
      investigators to locate additional reports. SELECTION CRITERIA: We considered
      randomized controlled trials (RCTs) that examined postpartum education about
      contraceptive use, whether delivered to individuals or to groups of women.
      Studies that randomized clusters rather than individuals were eligible if the
      investigators accounted for the clustering in the analysis. The intervention must
      have started within one month after delivery. DATA COLLECTION AND ANALYSIS: We
      assessed titles and abstracts identified during the literature searches. The data
      were abstracted and entered into Review Manager. Studies were examined for
      methodological quality. For dichotomous outcomes, the Mantel-Haenszel odds ratio
      (OR) with 95% confidence interval (CI) was calculated. Where data were sFor
      continuous variables, we computed the mean difference (MD) with 95% CI. Due to
      varied interventions and outcome measures, we did not conduct meta-analysis. MAIN
      RESULTS: Twelve trials met our eligibility criteria, included the three added in
      this update. The studies included a total of 4145 women. Eight trials were
      conducted in the USA; the others were from Australia, Nepal, Pakistan, and Syria.
      Four studies provided one session before hospital discharge; three had structured
      counseling of varying intensity and one involved informal counseling. Of eight
      interventions with than one contact, five focused on adolescents. Three of the
      five involved home visiting, one provided multiple clinic services, and one had
      in-person contact and phone follow-up. Of the remaining three for women of
      varying ages, two involved home visits and one provided phone follow-up.Our
      sensitivity analysis included six trials with evidence of moderate or high
      quality. In a study with adolescents, the group with home-based mentoring had
      fewer second births within two years compared to the control group (OR 0.41, 95%
      CI 0.17 to 1.00). The other five interventions had no effect. Of trials with
      lower quality evidence, two showed some effectiveness. In Nepal, women with an
      educational session immediately postpartum were more likely to use contraception
      at six months than those with a later or no session (OR 1.62, 95% CI 1.06 to
      2.50). In an Australian study, teenagers in a structured home-visiting program
      were more likely to have effective contraception use at six months than those
      with standard home visits (OR 3.24; 95% CI 1.35 to 7.79). AUTHORS' CONCLUSIONS:
      We focused our results summary on trials with moderate or high quality evidence.
      Overall, the overall quality of evidence in this review was moderate to low and
      the evidence of effectiveness was mostly low quality. The interventions could be
      improved by strengthening the program design and implementation. Some studies did
      not report program training for providers, adherence to the intervention
      protocol, or measurement of participants' knowledge and skills. Many trials did
      not have an objective outcome measure, i.e., pregnancy test or structured
      questionnaire for contraceptive use. Valid and reliable outcome measures are
      needed to obtain meaningful results. Still, given the associated costs and
      logistics, some programs would not be feasible in many settings.

PMID- 26222130
TI  - Optimal Arrangement of Four Short DNA Strands for Delivery of Immunostimulatory
      Nucleic Acids to Immune Cells.
AB  - Nanosized DNA assemblies are useful for delivering immunostimulatory cytosine
      phosphate-guanine (CpG) DNA to immune cells, but little is known about the
      optimal structure for such delivery. In this study, we designed three different
      DNA nanostructures using four 55-mer oligodeoxynucleotides (ODNs), that is,
      tetrapod-like structured DNA (tetrapodna), tetrahedral DNA (tetrahedron), and
      tetragonal DNA (tetragon), and compared their potencies. Electrophoresis showed
      that tetrapodna was obtained with high yield and purity, whereas tetrahedron
      formed multimers at high ODN concentrations. Atomic force microscopy revealed
      that all preparations were properly constructed under optimal conditions. The
      thermal stability of tetrapodna was higher than those of the others. Dynamic
      light scattering analysis showed that all of the assemblies were about 8 nm in
      diameter. Upon addition to mouse macrophage-like RAW264.7 cells, tetrahedron was
      most efficiently taken up by the cells. Then, a CpG DNA, a ligand for toll-like
      receptor 9, was linked to these DNA nanostructures and added to RAW264.7 cells.
      CpG tetrahedron induced the largest amount of tumor necrosis factor-alpha,
      followed by CpG tetrapodna. Similar results were obtained using human peripheral
      blood mononuclear cells. Taken together, these results indicate that tetrapodna
      is the best assembly with the highest yield and high immunostimulatory activity,
      and tetrahedron can be another useful assembly for cellular delivery if its
      preparation yield is improved.

PMID- 26222131
TI  - On the role of competent ligaments in vaginal surgery, pelvic floor and sexual
      function.

PMID- 26222132
TI  - Perfluorocarbon-Encapsulated PLGA-PEG Emulsions as Enhancement Agents for Highly
      Efficient Reoxygenation to Cell and Organism.
AB  - Perfluorocarbon (PFC), a kind of oxygen carrier, is encapsulated in PLGA-PEG to
      prepare a PLGA-PEG/PFC emulsion for highly efficient reoxygenation to cell and
      organism. HCT 116 cells are used as a model cell, whose viability has a
      significant enhancement after reoxygenation with PLGA-PEG/PFC emulsion because of
      the sufficient and timely oxygen supply. Meanwhile, hypoxia-reoxygenation injury
      will happen along with cell hypoxia-reoxygenation treatment, which is reflected
      by increasing reactive oxygen species (ROS) in cells. However, the integration of
      intracellular ROS and cell viability implies that the degree of hypoxia
      reoxygenation injury is sublethal to HCT116 cells when the concentration of PLGA
      PEG/PFC emulsion is lower than 0.2 mg/mL. Furthermore, the change of the
      expression level of hypoxia-inducible factor-1alpha (HIF-1alpha) is similar to
      that of cell viability during reoxygenation, which suggests that HIF-1alpha or
      its downstream proteins may make a significant contribution to cell viability. In
      vivo oxygen supply is assessed in rats through pulmonary delivery, which shows
      that PLGA-PEG/PFC emulsion can supply oxygen to rats and improve rats' lung
      ventilation. 

PMID- 26222134
TI  - Future prospect of insulin inhalation for diabetic patients: The case of Afrezza
      versus Exubera.
AB  - The current review was designed to compare between the insulin inhalation systems
      Exubera and Afrezza and to investigate the reasons why Exubera was unsuccessful,
      when Afrezza maker is expecting their product to be felicitous. In January 2006,
      Pfizer secured FDA and EC approval for the first of its kind, regular insulin
      through Exubera inhaler device for the management of types 1 and 2 diabetes
      mellitus (DM) in adults. The product was no longer available to the market after
      less than two years from its approval triggering a setback for competitive new
      inhalable insulins that were already in various clinical development phases. In
      contrary, MannKind Corporation started developing its ultra-rapid-acting insulin
      Afrezza in a bold bid, probably by managing the issues in which Exubera was not
      successful. Afrezza has been marketed since February, 2015 by Sanofi after
      getting FDA approval in June 2014. The results from this systematic review
      indicate the effectiveness of insulin inhalation products, particularly for
      patients initiating insulin therapy. Pharmaceutical companies should capitalize
      on the information available from insulin inhalation to produce competitive
      products that are able to match the bioavailability of subcutaneous (SC) insulin
      injection and to deal with the single insulin unit increments and basal insulin
      requirements in some diabetic patients or extending the horizon to inhalable drug
      products with completely different drug entities for other indications. 

PMID- 26222133
TI  - Cis-Antisense Transcription Gives Rise to Tunable Genetic Switch Behavior: A
      Mathematical Modeling Approach.
AB  - Antisense transcription has been extensively recognized as a regulatory mechanism
      for gene expression across all kingdoms of life. Despite the broad importance and
      extensive experimental determination of cis-antisense transcription, relatively
      little is known about its role in controlling cellular switching responses.
      Growing evidence suggests the presence of non-coding cis-antisense RNAs that
      regulate gene expression via antisense interaction. Recent studies also indicate
      the role of transcriptional interference in regulating expression of neighboring
      genes due to traffic of RNA polymerases from adjacent promoter regions. Previous
      models investigate these mechanisms independently, however, little is understood
      about how cells utilize coupling of these mechanisms in advantageous ways that
      could also be used to design novel synthetic genetic devices. Here, we present a
      mathematical modeling framework for antisense transcription that combines the
      effects of both transcriptional interference and cis-antisense regulation. We
      demonstrate the tunability of transcriptional interference through various
      parameters, and that coupling of transcriptional interference with cis-antisense
      RNA interaction gives rise to hypersensitive switches in expression of both
      antisense genes. When implementing additional positive and negative feed-back
      loops from proteins encoded by these genes, the system response acquires a
      bistable behavior. Our model shows that combining these multiple-levels of
      regulation allows fine-tuning of system parameters to give rise to a highly
      tunable output, ranging from a simple-first order response to biologically
      complex higher-order response such as tunable bistable switch. We identify
      important parameters affecting the cellular switch response in order to provide
      the design principles for tunable gene expression using antisense transcription.
      This presents an important insight into functional role of antisense
      transcription and its importance towards design of synthetic biological switches.

PMID- 26222135
TI  - Unique case of orbital myositis and dacryoadenitis preceding the vesicular rash
      of herpes zoster ophthalmicus.

PMID- 26222136
TI  - Unmet clinical needs in the management of advanced melanoma: findings from a
      survey of oncologists.
AB  - Advanced melanoma is a life-threatening cancer with limited life expectancy. The
      recent introduction of new targeted systemic therapies has provided clinicians
      with the means to potentially extend survival for the first time. However, the
      chance of cure remains very low and treatment-induced toxicity is well described.
      This qualitative study was undertaken to evaluate clinicians' assessment
      regarding the key concerns in managing advanced melanoma following the
      introduction of these new treatments. Three hundred and forty-three oncologists
      were surveyed online between August and November 2012 (in 11 countries) and March
      and April 2013 (in an additional country). Analysis of free-text responses
      identified 23 clinical issues of concern across all countries. Of these, the most
      common clinical concerns were drug toxicity and tolerability, followed by limited
      treatment effectiveness and limited treatment options. These results suggest that
      despite the promise of the two new agents in the field, clinicians are still
      concerned about the limitations of current treatment options, recognising that
      there remains a significant unmet need in the treatment of advanced melanoma. 

PMID- 26222137
TI  - Proteomic Analysis Provides New Insights in Phosphorus Homeostasis Subjected to
      Pi (Inorganic Phosphate) Starvation in Tomato Plants (Solanum lycopersicum L.).
AB  - Phosphorus is a major nutrient acquired by plants via high-affinity inorganic
      phosphate (Pi) transporters. To determine the adaptation and homeostasis strategy
      to Pi starvation, we compared the proteome analysis of tomato leaves that were
      treated with and without Pi (as KH2PO4) for 10 days. Among 600 reproducible
      proteins on 2-DE gels 46 of them were differentially expressed. These proteins
      were involved in major metabolic pathways, including photosynthesis,
      transcriptional/translational regulations, carbohydrate/energy metabolism,
      protein synthesis, defense response, and other secondary metabolism. The results
      also showed that the reduction in photosynthetic pigments lowered P content under
      -Pi treatments. Furthermore, high-affinity Pi transporters (lePT1 and lePT2)
      expressed in higher amounts under -Pi treatments. Also, the accumulation of Pi
      transporters was observed highly in the epidermis and palisade parenchyma under
      +Pi treatments compared to -Pi treatments. Our data suggested that tomato plants
      developed reactive oxygen species (ROS) scavenging mechanisms to cope with low Pi
      content, including the up-regulation of proteins mostly involved in important
      metabolic pathways. Moreover, Pi-starved tomato plants increased their internal
      Pi utilization efficiency by increasing the Pi transporter genes and their
      rational localization. These results thus provide imperative information about
      how tomato plants respond to Pi starvation and its homeostasis. 

PMID- 26222139
TI  - Dynamics of the Glycophorin A Dimer in Membranes of Native-Like Composition
      Uncovered by Coarse-Grained Molecular Dynamics Simulations.
AB  - Membranes are central for cells as borders to the environment or intracellular
      organelle definition. They are composed of and harbor different molecules like
      various lipid species and sterols, and they are generally crowded with proteins.
      The membrane system is very dynamic and components show lateral, rotational and
      translational diffusion. The consequence of the latter is that phase separation
      can occur in membranes in vivo and in vitro. It was documented that molecular
      dynamics simulations of an idealized plasma membrane model result in formation of
      membrane areas where either saturated lipids and cholesterol (liquid-ordered
      character, Lo) or unsaturated lipids (liquid-disordered character, Ld) were
      enriched. Furthermore, current discussions favor the idea that proteins are
      sorted into the liquid-disordered phase of model membranes, but experimental
      support for the behavior of isolated proteins in native membranes is sparse. To
      gain insight into the protein behavior we built a model of the red blood cell
      membrane with integrated glycophorin A dimer. The sorting and the dynamics of the
      dimer were subsequently explored by coarse-grained molecular dynamics
      simulations. In addition, we inspected the impact of lipid head groups and the
      presence of cholesterol within the membrane on the dynamics of the dimer within
      the membrane. We observed that cholesterol is important for the formation of
      membrane areas with Lo and Ld character. Moreover, it is an important factor for
      the reproduction of the dynamic behavior of the protein found in its native
      environment. The protein dimer was exclusively sorted into the domain of Ld
      character in the model red blood cell plasma membrane. Therefore, we present
      structural information on the glycophorin A dimer distribution in the plasma
      membrane in the absence of other factors like e.g. lipid anchors in a coarse
      grain resolution. 

PMID- 26222138
TI  - NRF2 Signaling Negatively Regulates Phorbol-12-Myristate-13-Acetate (PMA)-Induced
      Differentiation of Human Monocytic U937 Cells into Pro-Inflammatory Macrophages.
AB  - Blood monocytes are recruited to injured tissue sites and differentiate into
      macrophages, which protect against pathogens and repair damaged tissues. Reactive
      oxygen species (ROS) are known to be an important contributor to monocytes'
      differentiation and macrophages' function. NF-E2-related factor 2 (NRF2), a
      transcription factor regulating cellular redox homeostasis, is known to be a
      critical modulator of inflammatory responses. We herein investigated the role of
      NRF2 in macrophage differentiation using the human monocytic U937 cell line and
      phorbol-12-myristate-13-acetate (PMA). In U937 cells with NRF2 silencing, PMA
      stimulated cell adherence was significantly facilitated when compared to control
      U937 cells. Both transcript and protein levels for pro-inflammatory cytokines,
      including interleukine-1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha
      (TNFalpha) were highly elevated in PMA-stimulated NRF2-silenced U937 compared to
      the control. In addition, PMA-inducible secretion of monocyte chemotactic protein
      1 (MCP-1) was significantly high in NRF2-silenced U937. As an underlying
      mechanism, we showed that NRF2-knockdown U937 retained high levels of cellular
      ROS and endoplasmic reticulum (ER) stress markers expression; and subsequently,
      PMA-stimulated levels of Ca2+ and PKCalpha were greater in NRF2-knockdown U937
      cells, which caused enhanced nuclear accumulation of nuclear factor-?B (NF?B) p50
      and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation. Whereas the
      treatment of NRF2-silenced U937 cells with pharmacological inhibitors of NF?B or
      ERK1/2 largely blocked PMA-induced IL-1beta and IL-6 expression, indicating that
      these pathways are associated with cell differentiation. Taken together, our
      results suggest that the NRF2 system functions to suppress PMA-stimulated U937
      cell differentiation into pro-inflammatory macrophages and provide evidence that
      the ROS-PKCalpha-ERK-NF?B axis is involved in PMA-facilitated differentiation of
      NRF2-silenced U937 cells. 

PMID- 26222140
TI  - The Role of Protected Areas in the Avoidance of Anthropogenic Conversion in a
      High Pressure Region: A Matching Method Analysis in the Core Region of the
      Brazilian Cerrado.
AB  - Global efforts to avoid anthropogenic conversion of natural habitat rely heavily
      on the establishment of protected areas. Studies that evaluate the effectiveness
      of these areas with a focus on preserving the natural habitat define
      effectiveness as a measure of the influence of protected areas on total avoided
      conversion. Changes in the estimated effectiveness are related to local and
      regional differences, evaluation methods, restriction categories that include the
      protected areas, and other characteristics. The overall objective of this study
      was to evaluate the effectiveness of protected areas to prevent the advance of
      the conversion of natural areas in the core region of the Brazil's Cerrado Biome,
      taking into account the influence of the restriction degree, governmental sphere,
      time since the establishment of the protected area units, and the size of the
      area on the performance of protected areas. The evaluation was conducted using
      matching methods and took into account the following two fundamental issues:
      control of statistical biases caused by the influence of covariates on the
      likelihood of anthropogenic conversion and the non-randomness of the allocation
      of protected areas throughout the territory (spatial correlation effect) and the
      control of statistical bias caused by the influence of auto-correlation and
      leakage effect. Using a sample design that is not based on ways to control these
      biases may result in outcomes that underestimate or overestimate the
      effectiveness of those units. The matching method accounted for a bias reduction
      in 94-99% of the estimation of the average effect of protected areas on
      anthropogenic conversion and allowed us to obtain results with a reduced
      influence of the auto-correlation and leakage effects. Most protected areas had a
      positive influence on the maintenance of natural habitats, although wide
      variation in this effectiveness was dependent on the type, restriction,
      governmental sphere, size and age group of the unit. 

PMID- 26222141
TI  - Lasiodiplodins from mangrove endophytic fungus Lasiodiplodia sp. 318.
AB  - Four new lasiodiplodins (1-4), together with three known analogues, have been
      isolated from a mangrove endophytic fungus, Lasiodiplodia sp. 318#. Their
      structures were elucidated by spectroscopic techniques. Cytotoxic activities of
      compounds 1-7 were evaluated in vitro against human cancer lines THP1, MDA-MB
      435, A549, HepG2 and HCT-116. Compound 4 exhibited moderate cytotoxic activities.

PMID- 26222143
TI  - A Proteomic Analysis of Individual and Gender Variations in Normal Human Urine
      and Cerebrospinal Fluid Using iTRAQ Quantification.
AB  - Urine and cerebrospinal fluid (CSF) are two important biofluids used for disease
      biomarker discovery. For differential proteomic analysis, it is essential to
      evaluate individual and gender variations. In this study, we characterized
      urinary and CSF proteomes of 14 healthy volunteers with regard to individual and
      gender variations using 2DLC-MS/MS analysis and 8-plex iTRAQ quantification. A
      total of 968/512 urinary/CSF proteins were identified, with 406/280 quantified in
      all individuals. The median inter-individual coefficients of variation (CVs) were
      0.262 and 0.183 for urinary and CSF proteomes, respectively. Cluster analysis
      showed that male and female urinary proteomes exhibited different patterns,
      though CSF proteome showed no remarkable gender differences. In comparison with
      CSF proteome, urinary proteome showed higher individual variation. Further
      analysis revealed that individual variation was not correlated with protein
      abundance. The minimum sample size for proteomic analysis with a 2-fold change
      was 10 (4/5 for males/females using iTRAQ quantification) for urinary or 8 for
      CSF proteome. Intracellular proteins leaked from exfoliative cells tended to have
      higher CVs, and extracellular proteins secreted from urinary tract or originating
      from plasma tended to have lower CVs. The above results might be beneficial for
      differential proteomic analysis and biomarker discovery. 

PMID- 26222142
TI  - Predictors for MTB Culture-Positivity among HIV-Infected Smear-Negative
      Presumptive Tuberculosis Patients in Uganda: Application of New Tuberculosis
      Diagnostic Technology.
AB  - BACKGROUND: The existing World Health Organization diagnostic algorithms for
      smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics
      such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce
      delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought
      to determine predictors for MTB culture-positivity among these patients. METHODS:
      This study was nested into a prospective evaluation of HIV-infected outpatients
      and inpatients clinically suspected to have TB who were screened by smear
      microscopy on two spot sputum samples. Data on socio-demographics, clinical
      symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood
      cultures and TB-LAM were collected. Logistic regression and conditional inference
      tree analysis were used to determine the most predictive indicators for MTB
      culture-positivity. RESULTS: Of the 418 smear-negative participants [female, 64%;
      median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3],
      96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium
      tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001)
      and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were
      significantly associated with MTB culture-positivity. Previous TB treatment (aOR
      0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB
      culture. A conditional inference tree analysis showed that positive urine TB-LAM
      and abnormal CXR were the most predictive indicators of MTB culture-positivity. A
      combination of urine TB-LAM test and CXR had sensitivity and specificity of 50%
      and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with
      CD4<100 cells/mm3. CONCLUSIONS: A positive urine TB-LAM test and an abnormal CXR
      significantly predict MTB culture-positivity among smear-negative HIV-infected
      presumptive TB patients while previous TB treatment reduces the likelihood of a
      positive MTB culture. Validation studies to assess the performance of diagnostic
      algorithms that include urine TB-LAM in the diagnosis of smear-negative TB in HIV
      infected individuals are warranted.

PMID- 26222145
TI  - Bastimolide A, a Potent Antimalarial Polyhydroxy Macrolide from the Marine
      Cyanobacterium Okeania hirsuta.
AB  - Bastimolide A (1), a polyhydroxy macrolide with a 40-membered ring, was isolated
      from a new genus of the tropical marine cyanobacterium Okeania hirsuta. This
      novel macrolide was defined by spectroscopy and chemical reactions to possess one
      1,3-diol, one 1,3,5-triol, six 1,5-diols, and one tert-butyl group; however, the
      relationships of these moieties to one another were obscured by a highly
      degenerate (1)H NMR spectrum. Its complete structure and absolute configuration
      were therefore unambiguously determined by X-ray diffraction analysis of the nona
      p-nitrobenzoate derivative (1d). Pure bastimolide A (1) showed potent
      antimalarial activity against four resistant strains of Plasmodium falciparum
      with IC50 values between 80 and 270 nM, although with some toxicity to the
      control Vero cells (IC50 = 2.1 MUM), and thus represents a potentially promising
      lead for antimalarial drug discovery. Moreover, rigorous establishment of its
      molecular arrangement gives fresh insight into the structures and biosynthesis of
      cyanobacterial polyhydroxymacrolides. 

PMID- 26222144
TI  - Toll-Like Receptor 4 Engagement Mediates Prolyl Endopeptidase Release from Airway
      Epithelia via Exosomes.
AB  - Proteases are important regulators of pulmonary remodeling and airway
      inflammation. Recently, we have characterized the enzyme prolyl endopeptidase
      (PE), a serine peptidase, as a critical protease in the generation of the
      neutrophil chemoattractant tripeptide Pro-Gly-Pro (PGP) from collagen. However,
      PE has been characterized as a cytosolic enzyme, and the mechanism mediating PE
      release extracellularly remains unknown. We examined the role of exosomes derived
      from airway epithelia as a mechanism for PE release and the potential
      extracellular signals that regulate the release of these exosomes. We demonstrate
      a specific regulatory pathway of exosome release from airway epithelia and
      identify PE as novel exosome cargo. LPS stimulation of airway epithelial cells
      induces release of PE-containing exosomes, which is significantly attenuated by
      small interfering RNA depletion of Toll-like receptor 4 (TLR4). These differences
      were recapitulated upon intratracheal LPS administration in mice competent versus
      deficient for TLR4 signaling. Finally, sputum samples from subjects with cystic
      fibrosis colonized with Pseudomonas aeruginosa demonstrate elevated exosome
      content and increased PE levels. This TLR4-based mechanism highlights the first
      report of nonstochastic release of exosomes in the lung and couples TLR4
      activation with matrikine generation. The increased quantity of these proteolytic
      exosomes in the airways of subjects with chronic lung disease highlights a new
      mechanism of injury and inflammation in the pathogenesis of pulmonary disorders. 

PMID- 26222146
TI  - Reactivity of Nanoscale Zero-Valent Iron in Unbuffered Systems: Effect of pH and
      Fe(II) Dissolution.
AB  - While most published studies used buffers to maintain the pH, there is limited
      knowledge regarding the reactivity of nanoscale zerovalent iron (NZVI) in poorly
      buffered pH systems to date. In this work, the effect of pH and Fe(II)
      dissolution on the reactivity of NZVI was investigated during the reduction of 4
      nitrophenol (4-NP) in unbuffered pH systems. The reduction rate increased
      exponentially with respect to the NZVI concentration, and the ratio of dissolved
      Fe(II)/initial NZVI was related proportionally to the initial pH values,
      suggesting that lower pH (6-7) with low NZVI loading may slow the 4-NP reduction
      through acceleration of the dissolution of NZVI particles. Additional experiments
      using buffered pH systems confirmed that high pH values (8-9) can preserve the
      NZVI particles against dissolution, thereby enhancing the reduction kinetics of 4
      NP. Furthermore, reduction tests using ferrous ion in suspensions of magnetite
      and maghemite showed that surface-bound Fe(II) on oxide coatings can play an
      important role in enhancing 4-NP reduction by NZVI at pH 8. These unexpected
      results highlight the importance of pH and Fe(II) dissolution when NZVI
      technology is applied to poorly buffered systems, particularly at a low amount of
      NZVI (i.e., <0.075 g/L). 

PMID- 26222147
TI  - The impact of transcutaneous oxygen pressure measurement in patients with
      suspected critical lower limb ischemia.
AB  - BACKGROUND: Our aims were to describe macro- and microvascular disease by the use
      of a combination of toe blood pressure (TBP) and transcutaneous oxygen pressure
      (TcPO2) measurements, and through this approach we aimed to classify lower limb
      ulcers. One specific aim was to evaluate whether patients with diabetes had a
      more pronounced disturbance of the microcirculation compared to patients without
      known diabetes. METHODS: The study included a series of 498 patients with
      suspected critical lower limb ischemia. All patients were investigated with TBP
      and TcPO2, and the macro- and microvascular function was graded as normal,
      reduced or critically reduced. RESULTS: Four hundred and twenty-two patients
      (85%) had ulcerations at the time of the examination, the same percentage in
      patients with (254/300) and in patients without diabetes (168/198). Dominantly
      microvascular disease with TcPO2 more reduced than TBP was seen in 18% (54/300)
      of the diabetic, and in 17% (33/198) of the non-diabetic patients. In the
      diabetic patients the lower limb ulcerations were as following: 44% ischemic, 47%
      mixed and 9% non-ischemic, respectively. In the non-diabetic patients the
      corresponding numbers were 38%, 52% and 10%. CONCLUSIONS: By combining TBP and
      TcPO2 the degree of macro- and microvascular dysfunction can be evaluated,
      classification of lower limb ulcers will be facilitated and the risk of
      underestimation of the degree of distal ischemia will be reduced. Microvascular
      dysfunction is as common in non-diabetic patients, as it is in patients with
      diabetes.

PMID- 26222148
TI  - A novel approach to infrainguinal arteries with chronic total occlusions using
      the high frequency vibrational device.
AB  - BACKGROUND: Endovascular treatment (EVT) for chronic total occlusion (CTO) is a
      technically challenging problem in peripheral arterial disease (PAD). The Crosser
      system is a CTO device with high frequency vibrational energy to cross the CTO,
      which has been adopted for coronary CTO. We performed EVT procedure by the device
      for PAD with CTO, and the purpose of this study was to evaluate the efficacy and
      safety of a high-frequency vibrational device, the CrosserTM system, in the EVT
      for the infrainguinal arteries with CTO. METHODS: From April 2014 to September
      2014, 16 patients with 19 sites of infrainguinal CTO underwent EVT with the
      CrosserTM system and technique. CTO was defined as 100% occlusion of the vessel,
      and technical success was defined as the device's ability to facilitate the
      successful intraluminal delivery of the guidewire into the distal vessel. In
      addition, we evaluated the postoperative complications, including device-related
      complications. RESULTS: We treated 16 patients (12 males; mean age, 68+/-7 years)
      with a mean lesion length of CTO of 150+/-85 mm. A technical success rate of 84%
      was achieved, and no device-related complications were observed, including
      dissection and perforation. Technical failure was associated with hemodialysis
      and calcification of grade 3 (P=0.029 and 0.047, respectively). CONCLUSIONS: The
      CrosserTM system is a safe and effective treatment option for cases of
      infrainguinal CTO, without complications.

PMID- 26222149
TI  - Poly-ADP-ribosyl polymerase-14 promotes T helper 17 and follicular T helper
      development.
AB  - Transcription factors are critical determinants of T helper cell fate and require
      a variety of co-factors to activate gene expression. We previously identified the
      ADP ribosyl-transferase poly-ADP-ribosyl polymerase 14 (PARP-14) as a co-factor
      of signal transducer and activator of transcription (STAT) 6 that is important in
      B-cell and T-cell responses to interleukin-4, particularly in the differentiation
      of T helper type 2 (Th2) cells. However, whether PARP-14 functions during the
      development of other T helper subsets is not known. In this report we demonstrate
      that PARP-14 is highly expressed in Th17 cells, and that PARP-14 deficiency and
      pharmacological blockade of PARP activity result in diminished Th17
      differentiation in vitro and in a model of allergic airway inflammation. We
      further show that PARP-14 is expressed in T follicular helper (Tfh) cells and Tfh
      cell development is impaired in PARP-14-deficient mice following immunization
      with sheep red blood cells or inactivated influenza virus. Decreases in Th17 and
      Tfh development are correlated with diminished phospho-STAT3 and decreased
      expression of the interleukin-6 receptor alpha-chain in T cells. Together, these
      studies demonstrate that PARP-14 regulates multiple cytokine responses during
      inflammatory immunity. 

PMID- 26222150
TI  - Toward full spectrum speciation of silver nanoparticles and ionic silver by on
      line coupling of hollow fiber flow field-flow fractionation and minicolumn
      concentration with multiple detectors.
AB  - The intertransformation of silver nanoparticles (AgNPs) and ionic silver (Ag(I))
      in the environment determines their transport, uptake, and toxicity, demanding
      methods to simultaneously separate and quantify AgNPs and Ag(I). For the first
      time, hollow fiber flow field-flow fractionation (HF5) and minicolumn
      concentration were on-line coupled together with multiple detectors (including UV
      vis spectrometry, dynamic light scattering, and inductively coupled plasma mass
      spectrometry) for full spectrum separation, characterization, and quantification
      of various Ag(I) species (i.e., free Ag(I), weak and strong Ag(I) complexes) and
      differently sized AgNPs. While HF5 was employed for filtration and fractionation
      of AgNPs (>2 nm), the minicolumn packed with Amberlite IR120 resin functioned to
      trap free Ag(I) or weak Ag(I) complexes coming from the radial flow of HF5
      together with the strong Ag(I) complexes and tiny AgNPs (<2 nm), which were
      further discriminated in a second run of focusing by oxidizing >90% of tiny AgNPs
      to free Ag(I) and trapped in the minicolumn. The excellent performance was
      verified by the good agreement of the characterization results of AgNPs
      determined by this method with that by transmission electron microscopy, and the
      satisfactory recoveries (70.7-108%) for seven Ag species, including Ag(I), the
      adduct of Ag(I) and cysteine, and five AgNPs with nominal diameters of 1.4 nm, 10
      nm, 20 nm, 40 nm, and 60 nm in surface water samples. 

PMID- 26222151
TI  - Motor Sequence Learning and Consolidation in Unilateral De Novo Patients with
      Parkinson's Disease.
AB  - Previous research investigating motor sequence learning (MSL) and consolidation
      in patients with Parkinson's disease (PD) has predominantly included
      heterogeneous participant samples with early and advanced disease stages; thus,
      little is known about the onset of potential behavioral impairments. We employed
      a multisession MSL paradigm to investigate whether behavioral deficits in
      learning and consolidation appear immediately after or prior to the detection of
      clinical symptoms in the tested (left) hand. Specifically, our patient sample was
      limited to recently diagnosed patients with pure unilateral PD. The left hand
      symptomatic (LH-S) patients provided an assessment of performance following the
      onset of clinical symptoms in the tested hand. Conversely, right hand affected
      (left hand asymptomatic, LH-A) patients served to investigate whether MSL
      impairments appear before symptoms in the tested hand. LH-S patients demonstrated
      impaired learning during the initial training session and both LH-S and LH-A
      patients demonstrated decreased performance compared to controls during the next
      day retest. Critically, the impairments in later learning stages in the LH-A
      patients were evident even before the appearance of traditional clinical symptoms
      in the tested hand. Results may be explained by the progression of disease
      related alterations in relevant corticostriatal networks. 

PMID- 26222155
TI  - Systematic Analysis of the Molecular Mechanism Underlying Decidualization Using a
      Text Mining Approach.
AB  - Decidualization is a crucial process for successful embryo implantation and
      pregnancy in humans. Defects in decidualization during early pregnancy are
      associated with several pregnancy complications, such as pre-eclampsia,
      intrauterine growth restriction and recurrent pregnancy loss. However, the
      mechanism underlying decidualization remains poorly understood. In the present
      study, we performed a systematic analysis of decidualization-related genes using
      text mining. We identified 286 genes for humans and 287 genes for mice
      respectively, with an overlap of 111 genes shared by both species. Through
      enrichment test, we demonstrated that although divergence was observed, the
      majority of enriched gene ontology terms and pathways were shared by both
      species, suggesting that functional categories were more conserved than
      individual genes. We further constructed a decidualization-related protein
      protein interaction network consisted of 344 nodes connected via 1,541 edges. We
      prioritized genes in this network and identified 12 genes that may be key
      regulators of decidualization. These findings would provide some clues for
      further research on the mechanism underlying decidualization. 

PMID- 26222156
TI  - Glucagon Increases Beating Rate but Not Contractility in Rat Right Atrium.
      Comparison with Isoproterenol.
AB  - This study evaluated the chronotropic and inotropic responses to glucagon in
      spontaneously beating isolated right atria of rat heart. For comparison, we also
      investigated the effects resulting from stimulating beta-adrenoceptors with
      isoproterenol in this tissue. Isoproterenol increased both atrial frequency and
      contractility but glucagon only enhanced atrial rate. The transcript levels of
      glucagon receptors were about three times higher in sinoatrial node than in the
      atrial myocardium. Chronotropic responses to glucagon and isoproterenol were
      blunted by the funny current (If) inhibitor ZD 7288. Inhibitors of protein kinase
      A, H-89 and KT-5720 reduced the chronotropic response to glucagon but not to
      isoproterenol. Inhibition of ryanodine receptors and calcium/calmodulin dependent
      protein kinase II (important regulators of sarcoplasmic reticulum Ca2+ release),
      with ruthenium red and KN-62 respectively, failed to alter chronotropic responses
      of either glucagon or isoproterenol. Non selective inhibition of
      phosphodiesterase (PDE) with 3-isobutylmethylxantine or selective inhibition of
      PDE3 or PDE4 with cilostamide or rolipram respectively did not affect
      chronotropic effects of glucagon or isoproterenol. Our results indicate that
      glucagon increases beating rate but not contractility in rat right atria which
      could be a consequence of lower levels of glucagon receptors in atrial myocardium
      than in sinoatrial node. Chronotropic responses to glucagon or isoproterenol are
      mediated by If current but not by sarcoplasmic reticulum Ca2+ release, neither
      are regulated by PDE activity. 

PMID- 26222157
TI  - IL-27 Signaling Is Crucial for Survival of Mice Infected with African
      Trypanosomes via Preventing Lethal Effects of CD4+ T Cells and IFN-gamma.
AB  - African trypanosomes are extracellular protozoan parasites causing a chronic
      debilitating disease associated with a persistent inflammatory response.
      Maintaining the balance of the inflammatory response via downregulation of
      activation of M1-type myeloid cells was previously shown to be crucial to allow
      prolonged survival. Here we demonstrate that infection with African trypanosomes
      of IL-27 receptor-deficient (IL-27R-/-) mice results in severe liver
      immunopathology and dramatically reduced survival as compared to wild-type mice.
      This coincides with the development of an exacerbated Th1-mediated immune
      response with overactivation of CD4+ T cells and strongly enhanced production of
      inflammatory cytokines including IFN-gamma. What is important is that IL-10
      production was not impaired in infected IL-27R-/- mice. Depletion of CD4+ T cells
      in infected IL-27R-/- mice resulted in a dramatically reduced production of IFN
      gamma, preventing the early mortality of infected IL-27R-/- mice. This was
      accompanied by a significantly reduced inflammatory response and a major
      amelioration of liver pathology. These results could be mimicked by treating IL
      27R-/- mice with a neutralizing anti-IFN-gamma antibody. Thus, our data identify
      IL-27 signaling as a novel pathway to prevent early mortality via inhibiting
      hyperactivation of CD4+ Th1 cells and their excessive secretion of IFN-gamma
      during infection with African trypanosomes. These data are the first to
      demonstrate the essential role of IL-27 signaling in regulating immune responses
      to extracellular protozoan infections. 

PMID- 26222159
TI  - The Brazilian Association of Nursing in the uncompromising defense of the
      Brazilian Unified Health System.

PMID- 26222158
TI  - Randomized Controlled Trial on the Effect of Channa striatus Extract on
      Measurement of the Uterus, Pulsatility Index, Resistive Index of Uterine Artery
      and Superficial Skin Wound Artery in Post Lower Segment Caesarean Section Women.
AB  - AIM: To compare the mean of anteroposterior (AP) measurements of the uterus in
      longitudinal and oblique transverse planes, and the pulsatility index (PI) and
      resistive index (RI) of the uterine artery and superficial skin wound artery
      between patients taking Channa striatus and placebo. BACKGROUND: Channa striatus,
      also known as haruan, is a fresh water snakehead fish consumed in many parts of
      Southeast Asia. Channa striatus is also normally consumed by women postpartum to
      promote wound healing as well as to reduce post-operative pain. METHODOLOGY: This
      study is a randomised, double blind, placebo-controlled study conducted in women
      after Lower Segment Caesarean Section (LSCS). Subjects were randomised to either
      a Channa striatus or a placebo group and were given a daily dosage of 500 mg of
      Channa striatus extract or 500 mg maltodextrin, respectively, for six weeks post
      LSCS. The anteroposterior measurements of the uterus in the longitudinal and
      oblique transverse planes, and the pulsatility index (PI) and resistive index
      (RI) of the uterine and superficial skin wound arteries were assessed using
      pelvic Gray-scale ultrasound and Doppler ultrasound at baseline (Day 3) and at
      two weeks, four weeks and six weeks post-operatively. RESULTS: Sixty-six subjects
      were randomised into the study with 33 in the Channa striatus group and 33 in the
      placebo group. No significant differences were detected in terms of the
      pulsatility index (PI) and the resistive index (RI) of the uterine and
      superficial skin wound arteries between the Channa striatus and placebo groups.
      However, in the Channa striatus group, the AP measurements of the uterus on the
      longitudinal and oblique transverse planes were significantly lower compared to
      the placebo group (p<0.05 and p<0.001, respectively). CONCLUSION: Daily intake of
      Channa striatus extract results in marked differences compared to placebo in
      terms of uterine involution and recovery in women post LSCS. TRIAL REGISTRATION:
      www.isrctn.com 11960786.

PMID- 26222160
TI  - Relational skills and preserving patient privacy in the caring process.
AB  - OBJECTIVE: to analyze the development and mobilization of relational skills
      central to the caring process among nursing students throughout their
      professional training. METHOD: this was a quantitative study, descriptive and
      cross-sectional in design. The sample consisted of nursing undergraduate students
      from the Higher School of Health Sciences, in the city of Evora, Portugal. Data
      were collected using the previously validated Helping Relational Skills
      Inventory. RESULTS: the students gradually acquired "generic skills",
      "communication skills" and "contact skills", presenting the highest mean score in
      the last year of the program. However, the highest mean score for the "empathetic
      skills" subscale was presented by second-year students. CONCLUSION: age and year
      in program were found to be decisive variables regarding the acquisition of
      specific skills (empathetic and communication) by nursing students.

PMID- 26222161
TI  - Cross-cultural cultural adaptation of the "Nursing Students' Attitudes Toward
      Mental Health Nursing and Consumers" in Brazil.
AB  - OBJECTIVE: to make across-cultural adaptation of the "Nursing Students' Attitudes
      Toward Mental Health Nursing and Consumers" scale in Brazil. METHOD: the scale
      was tested regarding conceptual, item, semantic, and operational equivalence.
      RESULTS: content validation was conducted by an expert committee with a minimum
      consensus level of 80%. This process resulted in a 35-item scale divided into 6
      factors. The experts reached 100% consensus on the scale's clarity of language,
      practical pertinence and theoretical relevance, as well as on the need for
      excluding one factor. Data were collected in 2013 in the city of Londrina,
      Parana, Brazil. CONCLUSION: the instrument was cross-culturally adapted to
      Brazilian Portuguese and presented satisfactory content validity. We propose
      further studies on the scale's psychometric properties, such as construct
      validity, internal consistency and reliability.

PMID- 26222162
TI  - Perception of primary healthcare management nurses on the nursing process.
AB  - OBJECTIVE: this qualitative study aimed to analyze the perceptions of primary
      health care management nurses on the nursing process. METHOD: data were collected
      through interviews and analyzed by the Content Analysis proposed by Bardin's
      theoretical framework. RESULTS: managers recognize the importance of the nursing
      process, although its implementation was not a priority at the time of the
      interviews. A conceptual difficulty and a lack of understanding that the
      implementation of the care methodology should be a cross-departmental action in
      the local healthcare management were clearly observed. CONCLUSION: managers
      should have their perspectives broadened concerning the relevance of the nursing
      process and the professional training. The active participation of legislative
      nursing bodies, local healthcare management and the federal government may open
      the way for the effective implementation of the nursing process.

PMID- 26222163
TI  - Body mass index, waist circumference, and arterial hypertension in students.
AB  - OBJECTIVE: to investigate what is the best anthropometric predictor of arterial
      hypertension among private school students. METHOD: this was a cross-sectional
      study with 286 students between the ages of 10 and 14 from two private schools in
      the city of Paranavai, Parana, Brazil. The following variables were analyzed:
      body mass index, waist circumference and blood pressure. Statistical analysis was
      conducted with Pearson's partial correlation test and multivariate logistic
      regression, with p<0.05. RESULTS: both anthropometric indicators displayed weak
      correlation with systolic and diastolic levels, with coefficients (r) ranging
      from 0.27 to 0.36 (p < 0.001). Multivariate analysis showed that the only
      anthropometric indicator associated with arterial hypertension was waist
      circumference (OR= 2.3; 95% CI: 1.1-4.5), regardless of age or gender.
      CONCLUSION: this age group, waist circumference appeared to be a better predictor
      for arterial hypertension than body mass index.

PMID- 26222164
TI  - Critical incidents in nursing academics: discovering a new identity.
AB  - OBJECTIVE: a qualitative study that followed the principles of the grounded
      theory in order to analyze the professional identity of nursing academics through
      the analysis of the most disturbing critical incidents. METHOD: semi-structured
      interviews were conducted with seven nurses who worked as professors and
      researchers in a private university in Barcelona. RESULTS: the resulting
      empirical material was organized into two categories: characterization of
      critical incidents and responsiveness to the incident. CONCLUSION: the
      professional identity of nurses regarding the academic area is still under
      construction and inexperience is the major obstacle in the management of critical
      incidents in the teaching career.

PMID- 26222165
TI  - Mother recognition in the Neonatal Intensive Care Unit.
AB  - OBJECTIVE: analyze the maternal experience in a neonatal intensive care unit,
      focusing on relations of recognition. METHOD: a qualitative study, built on the
      perspective of Gadamer's hermeneutics, based on Honneth's concept of recognition.
      In-depth interviews were conducted with 10 mothers of children admitted to a
      neonatal intensive care unit. RESULTS: failures were reported in the process of
      mother recognition in the unit, with consequent feelings of insecurity and
      obligation to child care, resulting in fragility of self-esteem. CONCLUSION:
      interactions with health professionals in the NICU and its standards and
      protocols cause vulnerabilities and affect maternal recognition and autonomy.

PMID- 26222166
TI  - The work in prison: reflections on the health of prison officers.
AB  - OBJECTIVE: to understand the working conditions of prison officers and the
      repercutions of labor activity on their health. METHOD: qualitative and
      descriptive research. Data were collected through open interviews with the prison
      officers of a regional prision and the speeches were submitted to content
      analysis. RESULTS: the results showed unsatisfactory working conditions due to
      poor material resources and neglect of governmental regarding rehabilitation of
      convicts, resulting in workers' exposure to psychosocial risks, dissatisfaction,
      and emotional distress. CONCLUSION: investments on the security of workers may
      contribute to their health promotion.

PMID- 26222167
TI  - Vulnerability of families of elderly citizens cared for by the Family Health
      Strategy.
AB  - OBJECTIVE: the present descriptive, exploratory, cross-sectional study aimed to
      identify the vulnerability of families of elderly citizens cared for by the
      Family Health Strategy (FHS). METHOD: the research employed home interviews and
      was developed with a sample of 500 families of aged people cared for by 32 FHS
      teams in the city of Dourados, MS, Brazil. The Family Development Index (FDI) was
      adapted in order to classify the families according to their degree of
      vulnerability. RESULTS: the results revealed the presence of multigenerational
      families with low educational levels among individuals over the age of 20 and
      high illiteracy rates among elderly citizens. There were 403 families whose
      vulnerability was acceptable, 95 in severe vulnerability, and two families in a
      condition of very severe vulnerability. The most critical dimensions of the FDI
      were the access to knowledge and to work. CONCLUSION: the study identified that
      there is still a need for further investments that can assist these aged people
      and their families in the Primary Health Care.

PMID- 26222168
TI  - Manual for monitoring the quality of nursing home care records.
AB  - OBJECTIVE: to build and validate an instrument aimed at monitoring the quality of
      nursing records in the Home Care Program (HCP) of a university hospital. METHOD:
      methodological study involving the elaboration of a manual, whose content was
      later submitted to six experts for validation, reaching a >= 80% consensus. The
      data collection process was carried out in 2012 by means of a questionnaire
      comprised of the following issues: nursing evolution, nursing diagnosis, and
      nursing prescription, and standards for the nursing team recommended by the
      Regional Nursing Council of Sao Paulo and by the assessed institution. Manual
      items were judged according to the following variables: relevance, pertinence,
      clarity and simplicity. RESULTS: of the 39 propositions, 100% achieved >= 80%
      agreement in the relevance, pertinence and clarity variables; 92.3% in the
      simplicity variable. Sleep/rest, Mobility and Check-out variables did not reach a
      favorable minimum consensus in the prescribed activities and were improved
      following suggestions from the experts. CONCLUSION: we believe that the
      instrument will enable the improvement of the HCP's work process.

PMID- 26222169
TI  - Content analysis of a technology to the nursing diagnostic reasoning.
AB  - OBJECTIVE: to undergo a content analysis of a metacognitive strategy of indirect
      assessment in the pre-encounter with the client. METHOD: methodological study.
      Agreement and inter-rater reliability index for the criteria: relevance,
      adequacy, clarity, conciseness and accuracy of a technology to the nursing
      diagnosis reasoning for novices through an electronic form. The sample consisted
      of 13 raters. Data were analyzed using descriptive statistics. RESULTS: high
      agreement and inter-rater reliability for 85 items related to data collection
      stage and the strategy description. Only fi ve items did not reach the validation
      criteria and must be rewritten. CONCLUSION: indirect assessment of the pre
      encounter is relevant to the diagnostic reasoning process, being possible to
      develop competencies and diagnostic skills in the novice through strategies,
      proposals on innovative technology in the form of a diagram.

PMID- 26222170
TI  - Non-conventional technologies for data collection in Brazilian dissertations and
      theses.
AB  - OBJECTIVE: to characterize non-conventional technologies used for data collection
      of dissertations and theses available in the Catalog of Theses and Dissertations
      (CEPEn) of the Brazilian Nursing Association (ABEn). METHOD: this is a
      documentary research, whose data were collected in the catalogs of theses and
      dissertations available at the ABEn website, from Volumes XIX to XXI. The
      indicators collected were: academic level; educational institution; year;
      qualification of the author; setting; non-conventional technology used; type of
      technology; association with conventional techniques; methodological design;
      benefits and methodological limitations. RESULTS: from a total of 6346 studies,
      only 121 (1.91%) used non-conventional technologies for data collection,
      representing the fi nal sample of the study. CONCLUSION: it is concluded that
      Brazilian Nursing researches still need methodological innovations for data
      collection.

PMID- 26222171
TI  - Perception of nursing undergraduate students on self-aging.
AB  - OBJECTIVE: to analyze the perceptions of nursing undergraduate students on their
      self-aging process. METHOD: qualitative study carried out between August and
      September, 2011 with 18 nursing undergraduate students of a public university in
      Salvador, Bahia. The interviews were analyzed by means of the Content Analysis
      method. RESULTS: the following thematic concept was apprehended: Perceptions of
      nursing undergraduates on their self-aging, which generated two subcategories: A)
      The "don't think about it" process; B) The context influencing the process.
      CONCLUSION: undergraduates reveal that the aging process is an intrinsic factor
      to human development. Family ties, spirituality and physical activity would be
      key mechanisms toward active aging. However, students also reported that their
      accelerated and stressed social lifestyles led to inadequate habits, such as the
      consumption of fast food and alcohol, which become negative influences in their
      aging process.

PMID- 26222172
TI  - Symbolic effects capitalized by nurses from the National Institute of Cancer in
      Brazil (1980 - 1990).
AB  - OBJECTIVE: to describe the strategies of nurses in the National Institute of
      Cancer to disseminate its scientific capital and discuss the symbolic effects
      capitalized in the field of oncology in the 1980s. METHOD: historical social
      studies, with primary sources consisting of written documents and oral reports,
      and as secondary sources, articles and books on the subject, based on the French
      sociologist Pierre Bourdieu's concepts of scientific capital and habitus.
      RESULTS: it revealed the effective performance of nurses in this Institute on
      policies of cancer prevention and control and strategies used in the teaching of
      oncology nursing at the undergraduate level. In conclusion, nursing stands out in
      this context, through the dissemination of its scientific knowledge, as a
      participant in the construction of a scientific field of oncology nursing in
      Brazil, highlighting the occupation of important social areas.

PMID- 26222173
TI  - Weaknesses of vaccine storage in Primary Healthcare Centers.
AB  - OBJECTIVE: assessment through qualitative approach of vaccine storage in Primary
      Healthcare Centers. METHOD: assessment study of qualitative approach in which 30
      interviews were conducted with nurses, nursing technicians or assistants and
      technical reference in immunization, in 12 vaccine rooms that had 100% of the
      structural criteria evaluated. Recorded testimonials of the subjects were
      organized and analyzed using thematic Content Analysis. RESULTS: the assessment
      pointed to absence of knowledge on the parts of nurses and nursing technicians
      and assistants with respect to the effects of low temperature on vaccines.
      Barriers were also encountered in relation to the supervision of nurses in the
      vaccine room activities and in relation to the knowledge needed by workers to
      care for preservation of vaccines. CONCLUSION: vaccine storage is inadequate and
      may compromise the quality of the immunobiologicals dispensed to the populace.

PMID- 26222174
TI  - Knowledge and practice of the nurse about leprosy: actions of control and
      elimination.
AB  - OBJECTIVE: to assess the knowledge and practice of primary health care nurses
      about control and elimination actions of leprosy. METHOD: evaluation study with
      qualitative approach, using the Discourse of the Collective Subject, data were
      collected through semi-structured interviews conducted with 16 nurses. RESULTS:
      the data collected revealed that health professionals have sufficient knowledge
      about the National Policy on Control and Elimination of Leprosy (NPCEL) and that
      the main actions preconized were applied, however, notification of suspected or
      confirmed cases and social reintegration of the patient were not mentioned.
      CONCLUSION: keeping patients in treatment, overload of work, lack of
      interdisciplinarity and treatment performed at other locations outside of the
      community were difficulties reported by professionals. Nurses know the actions
      addressed at assistance of leprosy patients, however, the study points to the
      need for a practice which is more aligned to what advocates NPCEL.

PMID- 26222175
TI  - Risk assessment of patient falls while taking medications ordered in a teaching
      hospital.
AB  - OBJECTIVE: to stratify prescribed medication in a fall risk scale, identifying
      subgroups of drugs and inpatient units with higher risk of falls. METHOD:
      retrospective study on prescription order forms given by medical clinic, surgical
      clinic, and general intensive care unit. Risk factors under consideration: 1)
      orthostatic hypotension; 2) arterial hypotension; 3) arterial hypertension; 4)
      bradycardia; 5) psychomotor agitation; 6) mental confusion; 7) dizziness; 8)
      drowsiness/sedation; 9) reduced eyesight; 10) seizures; 11)
      atonia/dystonia/muscle weakness; 12) hypoglycemia; 13) urgent urination and 14)
      urgent defecation/diarrhea. Risk levels adopted: 0: 0 factor; I: 1-2 factors; II:
      3-5 factors; III: 6-9 factors; IV: 10-14 factors. RESULTS: 3893 drugs were
      analyzed and stratified in levels: 0 22.7%; I 33.5%; II 28%; III 15.1%; IV 0.7%.
      Levels III and IV more often refer to drugs for stomach acid disorders, 22.6%,
      and psycholeptics, 100%. CONCLUSION: knowing the risk factors associated with
      medication may help prevent and reduce falls, especially when therapeutic
      regimens cannot be modified.

PMID- 26222176
TI  - Evaluation of nursing students about learning with clinical simulation.
AB  - OBJECTIVE: to describe the contributions of clinical simulation for learning
      cognitive and procedural attributes through debriefing, from the perspective of
      nursing students. METHOD: descriptive exploratory study. Twenty nursing
      undergraduate students from a university in the interior of the state of Sao
      Paulo participated in this study. Data collection was performed at the debriefing
      stage. Student's perceptions about the simulation, positive aspects and what they
      could have done differently were registered. The students' statements were
      grouped according to the central themes and the framework of Bardin's content
      analysis (2011) and were analyzed using descriptive statistics. RESULTS:
      enhancement of active, critical and reflective learning (47.5%) was identified
      due to the closeness to reality in nursing care (20.3%), manifestation of
      feelings experienced during the simulation (15.3%) and composition of the
      scenario (15.3%). CONCLUSION: the clinical simulation followed by debriefing
      promotes the understanding of the link between action and achievements in
      learning.

PMID- 26222177
TI  - Nasal colonization in nursing professionals from units specialized in HIV/AIDS.
AB  - OBJECTIVE: to investigate the presence of microorganisms in the nostrils of the
      nursing professionals of a Brazilian teaching hospital. METHOD: cross-sectional
      study in two inpatient units specialized in HIV/AIDS. Nasal secretion samples of
      nursing professionals were collected in one month. The samples were processed at
      the microbiology laboratory of the institution and analyzed using the Statistical
      Package for the Social Sciences (SPSS) software, version 19.0. Ethical aspects
      were abided. RESULTS: from the 73 members of the nursing staff, samples of nasal
      secretions were collected from 61 (80.2%). Six types of microorganisms were
      isolated in 22 (41.0%) positive cultures. It is noteworthy that Staphylococcus
      aureus accounted for 22.9%, four of them oxacillin-resistant (MRSA). CONCLUSION:
      Staphylococcus aureus microorganism accounted for the largest prevalence in
      individuals of this study.

PMID- 26222178
TI  - Gender and violence against women in nursing literature: a review.
AB  - In the scientific production on inequalities in relationships between men and
      women, studies on violence against women and the urgency to recognize it as a
      public health problem stand out. OBJECTIVE: considering the potential of nursing
      to expand understanding on this theme, this study aims to learn what is being
      published on gender and violence against women in the main Brazilian nursing
      journals. METHOD: an integrative review of online publications between 2000 and
      2012 was conducted. Of the 138 articles selected, 25 addressed gender and
      violence against women as social constructs. RESULTS: there was a predominance of
      qualitative approaches (60%), empirical research (60%), academic (100%), authors
      who were nurses (96%), spousal violence (32%) and domestic violence (20%).
      Violence against women in the light of gender was associated in only 32% of the
      articles. CONCLUSION: there is a need for increased studies in partnership with
      the public health care service, and to expand discussions on the dynamics of
      power and resistance, which are the basis of the concept of gender.

PMID- 26222179
TI  - Comprehensive health care: dilemmas and challenges in nursing.
AB  - OBJECTIVE: this article discusses comprehensive care as a guiding tenet of the
      Brazilian Unified Health System (SUS), outlining health care practices,
      especially nursing, and the relationships built by subjects in action by means of
      different knowledge. METHODS: this is a theoretical reflection that aims to
      propose dimensions of analysis (access to services, reception, links, lines of
      care, accountability, and responsiveness), with an emphasis on the dilemmas and
      challenges of nursing. The proposed dimensions analyze the production of care and
      its political and technical aspects. CONCLUSION: care should be the focus of all
      health care work, bearing in mind that intervention for technological action of
      each profession goes beyond the core of isolated knowledge, as is the case of
      nursing, which is connected to other professional practices, and can peruse other
      territories that operate through relational technologies, entering into the world
      of the needs of users and families.

PMID- 26222180
TI  - Degradation and Stabilization of Peptide Hormones in Human Blood Specimens.
AB  - Plasma hormone peptides, including GLP-1, GIP, Glucagon, and OXM, possess
      multiple physiological roles and potential therapeutic and diagnostic utility as
      biomarkers in the research of metabolic disorders. These peptides are subject to
      proteolytic degradation causing preanalytical variations. Stabilization for
      accurate quantitation of these active peptides in ex vivo blood specimens is
      essential for drug and biomarker development. We investigated the protease-driven
      instability of these peptides in conventional serum, plasma, anticoagulated whole
      blood, as well as whole blood and plasma stabilized with protease inhibitors. The
      peptide was monitored by both time-course Matrix-Assisted Laser Desorption
      Ionization Time-to-Flight Mass Spectrometry (MALDI -TOF MS) and Ab-based assay
      (ELISA or RIA). MS enabled the identification of proteolytic fragments. In non
      stabilized blood samples, the results clearly indicated that dipeptidyl peptidase
      IV (DPP-IV) removed the N-terminal two amino acid residues from GLP-1, GIP and
      OXM(1-37) and not-yet identified peptidase(s) cleave(s) the full-length OXM(1-37)
      and its fragments. DPP-IV also continued to remove two additional N-terminal
      residues of processed OXM(3-37) to yield OXM(5-37). Importantly, both DPP-IV and
      other peptidase(s) activities were inhibited efficiently by the protease
      inhibitors included in the BD P800* tube. There was preservation of GLP-1, GIP,
      OXM and glucagon in the P800 plasma samples with half-lives > 96, 96, 72, and 45
      hours at room temperature (RT), respectively. In the BD P700* plasma samples, the
      stabilization of GLP-1 was also achieved with half-life > 96 hours at RT. The
      stabilization of these variable peptides increased their utility in drug and/or
      biomarker development. While stability results of GLP-1 obtained with Ab-based
      assay were consistent with those obtained by MS analysis, the Ab-based results of
      GIP, Glucagon, and OXM did not reflect the time-dependent degradations revealed
      by MS analysis. Therefore, we recommended characterizing the degradation of the
      peptide using the MS-based method when investigating the stability of a specific
      peptide. 

PMID- 26222182
TI  - Quasi-linear magnetoresistance and the violation of Kohler's rule in the quasi
      one-dimensional Ta4Pd3Te16 superconductor.
AB  - We report on the quasi-linear in field intrachain magnetoresistance in the normal
      state of a quasi-one-dimensional superconductor Ta4Pd3Te16 (Tc ~ 4.6 K). Both the
      longitudinal and transverse in-chain magnetoresistance shows a power-law
      dependence, Deltarho?B(alpha) with the exponent alpha close to 1 over a wide
      temperature and field range. The magnetoresistance shows no sign of saturation up
      to 50 T studied. The linear magnetoresistance observed in Ta4Pd3Te16 is found to
      be overall inconsistent with the interpretations based on the Dirac fermions in
      the quantum limit, charge conductivity fluctuations as well as quantum electron
      electron interference. Moreover, it is observed that the Kohler's rule,
      regardless of the field orientations, is violated in its normal state. This
      result suggests the loss of charge carriers in the normal state of this chain
      containing compound, due presumably to the charge-density-wave fluctuations.

PMID- 26222181
TI  - Nuclear hormone receptors put immunity on sterols.
AB  - Nuclear hormone receptors (NHRs) are transcription factors regulated by small
      molecules. The functions of NHRs range from development of primary and secondary
      lymphoid organs, to regulation of differentiation and function of DCs,
      macrophages and T cells. The human genome has 48 classic (hormone and vitamin
      receptors) and nonclassic (all others) NHRs; 17 nonclassic receptors are orphans,
      meaning that the endogenous ligand is unknown. Understanding the function of
      orphan NHRs requires the identification of their natural ligands. The mevalonate
      pathway, including its sterol and nonsterol intermediates and derivatives, is a
      source of ligands for many classic and nonclassic NHRs. For example, cholesterol
      biosynthetic intermediates (CBIs) are natural ligands for RORgamma/gammat. CBIs
      are universal endogenous metabolites in mammalian cells, and to study NHRs that
      bind CBIs requires ligand-free reporters system in sterol auxotroph cells.
      Furthermore, RORgamma/gammat shows broad specificity to sterol lipids, suggesting
      that RORgamma/gammat is either a general sterol sensor or specificity is defined
      by an abundant endogenous ligand. Unlike other NHRs, which regulate specific
      metabolic pathways, there is no connection between the genetic programs induced
      by RORgamma/gammat and ligand biosynthesis. In this review, we summarize the
      roles of nonclassic NHRs and their potential ligands in the immune system. 

PMID- 26222183
TI  - Lower Circulating C1q/TNF-Related Protein-3 (CTRP3) Levels Are Associated with
      Obesity: A Cross-Sectional Study.
AB  - PURPOSE: C1q/TNF-related protein-3 (CTRP3) is a novel adipokine that lowers blood
      glucose levels, reduces liver triglyceride synthesis, and is protective against
      hepatic steatosis in diet-induced obese mouse models. We hypothesized that higher
      circulating serum levels of CTRP3 would be associated with a lean body mass index
      (BMI) and a more favorable metabolic profile in humans. The aim of this study was
      to investigate CTRP3 levels in lean individuals compared to obese individuals.
      METHODS: This was a cross-sectional study of obese (n=44) and lean control
      patients (n=60). Fasting metabolic parameters were measured in all patients and
      serum CTRP3 levels were measured by ELISA. RESULTS: BMI of the lean group was
      21.9 +/- 0.2 kg/m2 and obese group was 45.2 +/- 1.1 kg/m2. We found significantly
      lower circulating levels of CTRP3 in obese individuals (405 +/- 8.3 vs. 436 +/-
      6.7 ng/mL, p=0.004) compared to the lean group. Serum CTRP3 levels were inversely
      correlated with BMI (p=0.001), and triglycerides (p<0.001), and significantly
      associated with gender (p<0.01), ethnicity (p=0.05), HDL-cholesterol (p<0.01),
      and adiponectin (p<0.01). We found BMI (p<0.01), gender (p<0.01), and ethnicity
      (p<0.05) to be significant predictors of CTRP3 levels when controlling for age in
      multiple regression analysis. CONCLUSIONS: CTRP3 is a beneficial adipokine whose
      circulating levels are significantly lower in obese individuals. Obesity causes
      dysregulation in adipokine production, including the down-regulation of CTRP3.
      Lower CTRP3 levels may contribute to the pathophysiology of metabolic disorders
      associated with obesity. Optimizing CTRP3 levels through novel therapies may
      improve obesity and its comorbidities.

PMID- 26222184
TI  - Focus on 16p13.3 Locus in Colon Cancer.
AB  - BACKGROUND: With one million new cases of colorectal cancer (CRC) diagnosed
      annually in the world, CRC is the third most commonly diagnosed cancer in the
      Western world. Patients with stage I-III CRC can be cured with surgery but are at
      risk for recurrence. Colorectal cancer is characterized by the presence of
      chromosomal deletions and gains. Large genomic profiling studies have however not
      been conducted in this disease. The number of a specific genetic aberration in a
      tumour sample could correlate with recurrence-free survival or overall survival,
      possibly leading to its use as biomarker for therapeutic decisions. At this point
      there are not sufficient markers for prediction of disease recurrence in
      colorectal cancer, which can be used in the clinic to discriminate between stage
      II patients who will benefit from adjuvant chemotherapy. For instance, the
      benefit of adjuvant chemotherapy has been most clearly demonstrated in stage III
      disease with an approximately 30 percent relative reduction in the risk of
      disease recurrence. The benefits of adjuvant chemotherapy in stage II disease are
      less certain, the risk for relapse is much smaller in the overall group and the
      specific patients at risk are hard to identify. MATERIALS AND METHODS: In this
      study, array-comparative genomic hybridization analysis (array-CGH) was applied
      to study high-resolution DNA copy number alterations in 93 colon carcinoma
      samples. These genomic data were combined with parameters like KRAS mutation
      status, microsatellite status and clinicopathological characteristics. RESULTS:
      Both large and small chromosomal losses and gains were identified in our sample
      cohort. Recurrent gains were found for chromosome 1q, 7, 8q, 13 and 20 and losses
      were mostly found for 1p, 4, 8p, 14, 15, 17p, 18, 21 and 22. Data analysis
      demonstrated that loss of chromosome 4 is linked to a worse prognosis in our
      patients series. Besides these alterations, two interesting small regions of
      overlap were identified, which could be associated with disease recurrence. Gain
      of the 16p13.3 locus (including the RNA binding protein, fox-1 homolog gene,
      RBFOX1) was linked with a worse recurrence-free survival in our patient cohort.
      On the other hand, loss of RBFOX1 was only found in patients without disease
      recurrence. Most interestingly, above mentioned characteristics were also found
      in stage II patients, for whom there is a high medical need for the
      identification of new prognostic biomarkers. CONCLUSIONS: In conclusion, copy
      number variation of the 16p13.3 locus seems to be an important parameter for
      prediction of disease recurrence in colon cancer.

PMID- 26222185
TI  - Modulation of the EMT/MET process by pyrrole-imidazole polyamide targeting human
      transforming growth factor-beta1.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a potent induction factor for
      epithelial-mesenchymal transition (EMT). Mesenchymal-epithelial transition (MET),
      as the inverse process of EMT, has recently been reported to promote the
      induction of induced pluripotent stem cells (iPSCs). We have developed pyrrole
      imidazole (PI) polyamide, a novel gene regulator that targets human TGF-beta1,
      and investigated its effects on the EMT/MET process. PI polyamide targeted to TGF
      beta1 significantly inhibited the mRNA expression of TGF-beta1 and SNAI1 as an
      EMT marker and increased mRNA and protein expression of E-cadherin in human
      epithelial cells. To enhance the induction of iPSCs by the MET process, PI
      polyamide targeted to TGF-beta1 was applied to human fibroblasts transfected with
      exogenous reprogramming factors by Sendai virus vector and grown in human iPSCs.
      The PI polyamide significantly increased the number of alkaline phosphatase
      positive colonies. The expression of undifferentiated markers was also observed
      in these colonies. These results suggest that PI polyamide targeted to human TGF
      beta is a novel compound that can control the EMT/MET process of human epithelial
      cells and enhance the induction of human fibroblasts to iPSCs. 

PMID- 26222186
TI  - AKT mediated glycolytic shift regulates autophagy in classically activated
      macrophages.
AB  - Autophagy is considered as an innate defense mechanism primarily due to its role
      in the targeting of intracellular pathogens for lysosomal degradation. Here we
      report inhibition of autophagy as an adaptive response in classically activated
      macrophages that helps achieve high cellular ROS production and cell death
      another hallmark of innate mechanisms. We show prolonged classical activation of
      Raw 264.7 macrophages by treating them with IFN-gamma and LPS inhibited
      autophagy. The inhibition of autophagy was dependent on nitric oxide (NO)
      production which activated the AKT-mTOR signaling, the known negative regulators
      of autophagy. Autophagy inhibition in these cells was accompanied with a shift to
      aerobic glycolysis along with a decline in the mitochondrial membrane potential
      (MOMP). The decline in MOMP coupled with autophagy inhibition led to increased
      mitochondrial content and considerably elevated cellular ROS, eventually causing
      cell death. Next, using specific siRNA mediated knockdowns we show AKT was
      responsible for the glycolytic shift and autophagy inhibition in activated
      macrophages. Surprisingly, AKT knockdown in activated macrophages also rescued
      them from cell death. Finally we show that AKT mediated autophagy inhibition in
      the activated macrophages correlated with the depletion of glucose from the
      extracellular medium, and glucose supplementation not only rescued autophagy
      levels and reversed other phenotypes of activated macrophages, but also inhibited
      cell death. Thus we report here a novel link between AKT mediated glycolytic
      metabolism and autophagy in the activated macrophages, and provide a possible
      mechanism for sustained macrophage activation in vivo. 

PMID- 26222187
TI  - Influence of flow velocity on biofilm growth in a tubular heat exchanger
      condenser cooled by seawater.
AB  - The influence of flow velocity (FV) on the heat transfer process in tubes made
      from AISI 316L stainless steel in a heat exchanger-condenser cooled by seawater
      was evaluated based on the characteristics of the resulting biofilm that adhered
      to the internal surface of the tubes at velocities of 1, 1.2, 1.6, and 3 m s(-1).
      The results demonstrated that at a higher FV, despite being more compact and
      consistent, the biofilm was thinner with a lower concentration of solids, and
      smoother, which favoured the heat transfer process within the equipment. However,
      higher velocities increase the initial cost of the refrigerating water-pumping
      equipment and its energy consumption cost to compensate for the greater pressure
      drops produced in the tube. The velocity of 1.6 m s(-1) represented the
      equilibrium between the advantages and disadvantages of the variables analysed
      for the test conditions in this study. 

PMID- 26222189
TI  - Membrane topology of Golgi-localized probable S-adenosylmethionine-dependent
      methyltransferase in tobacco (Nicotiana tabacum) BY-2 cells.
AB  - S-adenosylmethionine (SAM)-dependent methyltransferases (MTases) transfer methyl
      groups to substrates. In this study, a novel putative tobacco SAM-MTase termed
      Golgi-localized methyl transferase 1 (GLMT1) has been characterized. GLMT1 is
      comprised of 611 amino acids with short N-terminal region, putative transmembrane
      region, and C-terminal SAM-MTase domain. Expression of monomeric red fluorescence
      protein (mRFP)-tagged protein in tobacco BY-2 cell indicated that GLMT1 is a
      Golgi-localized protein. Analysis of the membrane topology by protease digestion
      suggested that both C-terminal catalytic region and N-terminal region seem to be
      located to the cytosolic side of the Golgi apparatus. Therefore, GLMT1 might have
      a different function than the previously studied SAM-MTases in plants. 

PMID- 26222188
TI  - Effects of Ankle Arthrodesis on Biomechanical Performance of the Entire Foot.
AB  - BACKGROUND/METHODOLOGY: Ankle arthrodesis is one popular surgical treatment for
      ankle arthritis, chronic instability, and degenerative deformity. However,
      complications such as foot pain, joint arthritis, and bone fracture may cause
      patients to suffer other problems. Understanding the internal biomechanics of the
      foot is critical for assessing the effectiveness of ankle arthrodesis and
      provides a baseline for the surgical plan. This study aimed to understand the
      biomechanical effects of ankle arthrodesis on the entire foot and ankle using
      finite element analyses. A three-dimensional finite element model of the foot and
      ankle, involving 28 bones, 103 ligaments, the plantar fascia, major muscle
      groups, and encapsulated soft tissue, was developed and validated. The
      biomechanical performances of a normal foot and a foot with ankle arthrodesis
      were compared at three gait instants, first-peak, mid-stance, and second-peak.
      PRINCIPAL FINDINGS/CONCLUSIONS: Changes in plantar pressure distribution, joint
      contact pressure and forces, von Mises stress on bone and foot deformation were
      predicted. Compared with those in the normal foot, the peak plantar pressure was
      increased and the center of pressure moved anteriorly in the foot with ankle
      arthrodesis. The talonavicular joint and joints of the first to third rays in the
      hind- and mid-foot bore the majority of the loading and sustained substantially
      increased loading after ankle arthrodesis. An average contact pressure of 2.14
      MPa was predicted at the talonavicular joint after surgery and the maximum
      variation was shown to be 80% in joints of the first ray. The contact force and
      pressure of the subtalar joint decreased after surgery, indicating that arthritis
      at this joint was not necessarily a consequence of ankle arthrodesis but rather a
      progression of pre-existing degenerative changes. Von Mises stress in the second
      and third metatarsal bones at the second-peak instant increased to 52 MPa and 34
      MPa, respectively, after surgery. These variations can provide indications for
      outcome assessment of ankle arthrodesis surgery.

PMID- 26222190
TI  - Semiconducting quaternary chalcogenide glasses as new potential thermoelectric
      materials: an As-Ge-Se-Sb case.
AB  - The performance of thermoelectric materials may be improved via complex
      structures, impurities, disorder etc. Chalcogenide glasses possess such
      properties. In the present paper, we report the electrical and thermoelectric
      properties of As14Ge14Se72-xSbx (where x = 3, 6, 9, 12, 15 at%) chalcogenide
      glasses in the temperature range of 300 K-450 K. The electrical conductivity has
      been observed to increase from 1.46 * 10(-9) Omega(-1) cm(-1) to 1.80 * 10(-6)
      Omega(-1) cm(-1) for x = 3 at% to x = 15 at%. The addition of Sb increases the
      Seebeck coefficient to a large value of 1124 MUV K(-1) for x = 15 at% at 333 K.
      As a result of increased electrical conductivity and Seebeck coefficient for
      enhanced values of Sb, the power factor (a measure of the performance of the
      thermoelectric energy converters) has been observed to increase strongly. Results
      indicate that the investigated chalcogenide glassy compositions may be potential
      candidates for incurring high action thermoelectric materials. 

PMID- 26222196
TI  - Predicting Molecular Targets for Small-Molecule Drugs with a Ligand-Based
      Interaction Fingerprint Approach.
AB  - The computational prediction of molecular targets for small-molecule drugs
      remains a great challenge. Herein we describe a ligand-based interaction
      fingerprint (LIFt) approach for target prediction. Together with physics-based
      docking and sampling methods, we assessed the performance systematically by
      modeling the polypharmacology of 12 kinase inhibitors in three stages. First, we
      examined the capacity of this approach to differentiate true targets from false
      targets with the promiscuous binder staurosporine, based on native complex
      structures. Second, we performed large-scale profiling of kinase selectivity on
      the clinical drug sunitinib by means of computational simulation. Third, we
      extended the study beyond kinases by modeling the cross-inhibition of bromodomain
      containing protein 4 (BRD4) for 10 well-established kinase inhibitors. On this
      basis, we made prospective predictions by exploring new kinase targets for the
      anticancer drug candidate TN-16, originally known as a colchicine site binder and
      microtubule disruptor. As a result, p38alpha was highlighted from a panel of 187
      different kinases. Encouragingly, our prediction was validated by an in vitro
      kinase assay, which showed TN-16 as a low-micromolar p38alpha inhibitor.
      Collectively, our results suggest the promise of the LIFt approach in predicting
      potential targets for small-molecule drugs. 

PMID- 26222195
TI  - A Ligand-Based Drug Design. Discovery of 4-Trifluoromethyl-7,8-pyranocoumarin as
      a Selective Inhibitor of Human Cytochrome P450 1A2.
AB  - In humans, cytochrome P450 1A2 is the major enzyme metabolizing environmental
      arylamines or heterocyclic amines into carcinogens. Since evidence shows that
      planar triangle-shaped molecules are capable of selectively inhibiting P450 1A2,
      16 triangular flavone, and coumarin derivatives were designed and synthesized for
      these studies. Among these compounds, 7,8-furanoflavone time-dependently inhibits
      P450 1A2 with a K(I) value of 0.44 MUM. With a 5 min preincubation in the
      presence of NADPH, 0.01 MUM 7,8-furanoflavone completely inactivates P450 1A2 but
      does not influence the activities of P450s 1A1 and 1B1. Another target compound,
      7,8-pyrano-4-trifluoromethylcoumarin, is found to be a competitive inhibitor,
      showing high selectivity for the inhibition of P450 1A2 with a K(i) of 0.39 MUM,
      155- and 52-fold lower than its K(i) values against P450s 1A1 and 1B1,
      respectively. In yeast AhR activation assays, 7,8-pyrano-4
      trifluoromethylcoumarin does not activate aryl hydrocarbon receptor when the
      concentration is lower than 1 MUM, suggesting that this compound would not up
      regulate AhR-caused P450 enzyme expression. In-cell P450 1A2 inhibition assays
      show that 7,8-pyrano-4-trifluoromethylcoumarin decreases the MROD activity in
      HepG2 cells at concentrations higher than 1 MUM. Thus, using 7,8-pyrano-4
      trifluoromethylcoumarin, a selective and specific P450 1A2 action suppression
      could be achieved, indicating the potential for the development of P450 1A2
      targeting cancer preventive agents.

PMID- 26222197
TI  - Endogenous adenosine release is involved in the control of heart rate in rats.
AB  - Intravenous (i.v.) injections of adenosine exert marked effects on heart rate
      (HR) and arterial blood pressure (BP), but the role of an endogenous adenosine
      release by vagal stimulation has not been evaluated. In anaesthetized rats, we
      examined HR and BP changes induced by 1 min electrical vagal stimulation in the
      control condition, and then after i.v. injections of (i) atropine, (ii)
      propranolol, (iii) caffeine, (iv) 8 cyclopentyl-1,3-dipropylxanthine (DPCPX), or
      (v) dipyridamole to increase the plasma concentration of adenosine (APC). APC was
      measured by chromatography in the arterial blood before and at the end of vagal
      stimulation. The decrease in HR in the controls during vagal stimulation was
      markedly attenuated, but persisted after i.v. injections of atropine and
      propranolol. When first administered, DPCPX modestly but significantly reduced
      the HR response to vagal stimulation, but this disappeared after i.v. caffeine
      administration. Both the HR and BP responses were significantly accentuated after
      i.v. injection of dipyridamole. Vagal stimulation induced a significant increase
      in APC, proportional to the magnitude of HR decrease. Our data suggest that the
      inhibitory effects of electrical vagal stimulations on HR and BP were partly
      mediated through the activation of A1 and A2 receptors by an endogenous adenosine
      release. Our experimental data could help to understand the effects of ischemic
      preconditioning, which are partially mediated by adenosine.

PMID- 26222198
TI  - The effect of an intense mentoring program on junior investigators' preparation
      for a patient-oriented clinical research career.
AB  - PROBLEM: There is a recognized need to translate scientific discoveries to
      patient-oriented clinical research (POCR). Several obstacles interfere with the
      successful recruitment and retention of physicians for POCR careers. APPROACH:
      The American Society of Hematology developed a yearlong educational and mentoring
      experience, the Clinical Research Training Institute (CRTI), for early-career
      physician-scientists from multiple institutions throughout the United States and
      Canada pursuing POCR careers. Several academic outcome measures of the 140
      participants in the first seven years (2003-2010) of CRTI were evaluated by
      reviewing former trainee participants' curriculum vitae and survey responses.
      OUTCOMES: Ethnic, racial, and gender diversity of CRTI trainees was reflective of
      the proportions represented across U.S. hematology/oncology fellowship programs.
      Eighty-six percent (109/126) of trainees reported success establishing a POCR
      study; nearly half (62/126) had primarily research-focused jobs. Former CRTI
      trainees received at least 262 external grant awards and published 1,035 peer
      reviewed manuscripts, 173 chapters, and 115 review articles. NEXT STEPS: Because
      mentorship is key to developing a successful career, the CRTI program is being
      modified to enhance longitudinal mentorship by CRTI faculty mentors and mentors
      at trainees' home institutions, as well as to encourage the establishment of
      collaborations and the potential for research project success. Efforts to make
      the CRTI experience available to more phy sicians, include more CRTI graduates as
      faculty, and increase participation by hematologists from backgrounds under
      represented in medicine are under way.

PMID- 26222199
TI  - Interconversion between Superatomic 6-Electron and 8-Electron Configurations of
      M@Au24(SR)18 Clusters (M = Pd, Pt).
AB  - The exceptional stability of thiolate-protected Au25 clusters, [Au25(SR)18](-),
      arises from the closure of superatomic electron shells, leading to a noble-gas
      like 8-electron configuration (1S(2)1P(6)). Here we present that replacing the
      core Au atom with Pd or Pt results in stable [MAu24(SR)18](0) clusters (M = Pd,
      Pt) having a superatomic 6-electron configuration (1S(2)1P(4)). Voltammetric
      studies of [PdAu24(SR)18](0) and [PtAu24(SR)18](0) reveal that the highest
      occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gaps
      of these clusters are 0.32 and 0.29 eV, respectively, indicating their electronic
      structures are drastically altered upon doping of the foreign metal. Density
      functional investigations confirm that the HOMO-LUMO gaps of these clusters are
      indeed smaller, respectively 0.33 and 0.32 eV, than that of [Au25(SR)18](-) (1.35
      eV). Analysis of the optimized geometries for the 6-electron [MAu24(SR)18](0)
      clusters shows that the MAu12 core is slightly flattened to yield an oblate
      ellipsoid. The drastically decreased HOMO-LUMO gaps observed are therefore the
      result of Jahn-Teller-like distortion of the 6-electron [MAu24(SR)18](0)
      clusters, accompanying splitting of the 1P orbitals. These clusters become 8
      electron [MAu24(SR)18](2-) clusters upon electronic charging, demonstrating
      reversible interconversion between the 6-electron and 8-electron configurations
      of MAu24(SR)18. 

PMID- 26222200
TI  - Determining When Patients Need Transfusions.

PMID- 26222201
TI  - Do field position and playing standard influence athlete performance in
      wheelchair basketball?
AB  - Improved understanding of mobility performance in wheelchair basketball is
      required to increase game performance. The aim of this study was to quantify the
      wheelchair-athlete activities of players in different field positions and of
      different playing standard during wheelchair basketball matches. From video
      analysis, absolute and relative duration and frequency of wheelchair movements
      and athlete control options were examined in 27 national standard and 29
      international standard players during entire wheelchair basketball matches.
      Between-group factorial analysis of variances identified that national players
      drove more forward (42.6 +/- 6.8 vs. 35.4 +/- 3.7%; effect size Cohen's d (ES) =
      1.48) and started more often driving forward (33.9 +/- 2.6 vs. 31.8 +/- 2.8; ES =
      0.77) during a match while the mean activity duration for a single driving
      forward activity was longer (4.3 +/- 0.9 vs. 3.7 +/- 0.6 s; ES = 0.75) than for
      international players. Furthermore, national players performed fewer rotational
      movements (21.8 +/- 4.0 vs. 28.9 +/- 7.8%; ES = -1.30) and started less often
      with the rotational movements (35.0 +/- 3.6 vs. 40.5 +/- 5.5; ES = -1.21) while
      the mean activity duration for a single rotation activity was shorter (2.1 +/-
      0.3 vs. 2.3 +/- 0.3 s; ES = -0.67) than for international players. Differences in
      mobility performance among guard, forward and centre players were minimal. The
      results should help wheelchair basketball coaches specify wheelchair-handling
      training techniques and means to optimise wheelchair-athlete configurations. 

PMID- 26222202
TI  - Population pharmacokinetics of meropenem during continuous infusion in surgical
      ICU patients.
AB  - Continuous infusion of meropenem is a candidate strategy for optimization of its
      pharmacokinetic/pharmacodynamic profile. However, plasma concentrations are
      difficult to predict in critically ill patients. Steady-state concentrations of
      meropenem were determined prospectively during continuous infusion in 32 surgical
      ICU patients (aged 21-85 years, body weight 55-125 kg, APACHE II 5-29, measured
      creatinine clearance 22.7-297 mL/min). Urine was collected for the quantification
      of renal clearance of meropenem and creatinine. Cystatin C was measured as an
      additional marker of renal function. Population pharmacokinetic models were
      developed using NONMEM((r)) , which described total meropenem clearance and its
      relationship with several estimates of renal function (measured creatinine
      clearance CLCR , Cockcroft-Gault formula CLCG , Hoek formula, 1/plasma
      creatinine, 1/plasma cystatin C) and other patient characteristics. Any estimate
      of renal function improved the model performance. The strongest association of
      clearance was found with CLCR (typical clearance = 11.3 L/h * [1 + 0.00932 *
      (CLCR  - 80 mL/min)]), followed by 1/plasma cystatin C; CLCG was the least
      predictive covariate. Neither age, weight, nor sex was found to be significant.
      These models can be used to predict dosing requirements or meropenem
      concentrations during continuous infusion. The covariate CLCR offers the best
      predictive performance; if not available, cystatin C may provide a promising
      alternative to plasma creatinine. 

PMID- 26222203
TI  - ABCA3 lung disease in an ex 27 week preterm infant responsive to systemic
      glucocorticosteroids.
AB  - We present a case of an infant born at almost 28 weeks gestation, found to be
      homozygous for a missense mutation of ABCA3, with diffuse lung disease that has
      continued throughout infancy. The patient's clinical course and chest imaging was
      highly suggestive of diffuse lung disease of infancy, and not of chronic lung
      disease of prematurity. The lung disease proved to be highly responsive to
      systemic corticosteroids. This is a case of ABCA3 lung disease that demonstrated
      improvement after systemic glucocorticosteroid administration.

PMID- 26222204
TI  - The Notch-mediated hyperplasia circuitry in Drosophila reveals a Src-JNK
      signaling axis.
AB  - Notch signaling controls a wide range of cell fate decisions during development
      and disease via synergistic interactions with other signaling pathways. Here,
      through a genome-wide genetic screen in Drosophila, we uncover a highly complex
      Notch-dependent genetic circuitry that profoundly affects proliferation and
      consequently hyperplasia. We report a novel synergistic relationship between
      Notch and either of the non-receptor tyrosine kinases Src42A and Src64B to
      promote hyperplasia and tissue disorganization, which results in cell cycle
      perturbation, JAK/STAT signal activation, and differential regulation of Notch
      targets. Significantly, the JNK pathway is responsible for the majority of the
      phenotypes and transcriptional changes downstream of Notch-Src synergy. We
      previously reported that Notch-Mef2 also activates JNK, indicating that there are
      commonalities within the Notch-dependent proliferation circuitry; however, the
      current data indicate that Notch-Src accesses JNK in a significantly different
      fashion than Notch-Mef2. 

PMID- 26222206
TI  - Enhancement of angiogenic effects by hypoxia-preconditioned human umbilical cord
      derived mesenchymal stem cells in a mouse model of hindlimb ischemia.
AB  - It has been studied that mesenchymal stem cells (MSCs) have the capability to
      promote angiogenesis. Furthermore, there is strong evidence that hypoxic
      conditions can enhance angiogenesis and immune modulation mediated by MSCs, a
      notion that has been applied in many fields of clinical application. In the
      present study, we compared the efficacy of hypoxia preconditioned human umbilical
      cord-derived mesenchymal stem cells (hUC-MSCs) and normoxia conditioned hUC-MSCs
      for the treatment of ischemic injury in hindlimbs of an immunodeficient mouse
      model. Expression of negative markers for MSC such as CD31, CD34, and CD45 or
      positive markers such as CD44, CD73, CD90, and CD105 was not significantly
      changed in hypoxia preconditioned hUC-MSCs compared with hUC-MSCs cultured in
      normoxic condition. Expression of angiogenesis-related genes such as COX-2, VEGF,
      Tie-2, and TGF-beta1 was increased compared with hUC-MSCs cultured in normoxic
      conditions. In the in vivo model, CD31 expression as a marker of angiogenesis was
      significantly increased in the ischemic limbs at 1 month after injection with
      hypoxic hUC-MSCs. Angiogenesis-related genes such as Ang-1, COX-1, PIGF, and MCP
      1 were significantly upregulated in the muscle of ischemic hindlimbs treated with
      hypoxic hUC-MSCs than normoxic hUC-MSCs. Expression of proinflammatory genes such
      as IL-1, and IL-20 was reduced, whereas TGF-beta1, which has an anti-inflammatory
      effect, was strongly increased. In conclusion, hypoxic culture conditions could
      induce expression of angiogenesis related genes in hUC-MSCs, and hypoxia
      preconditioned hUC-MSCs showed enhancing effects by inducing angiogenesis and low
      inflammatory immune response compared with normoxic hUC-MSCs in the ischemia
      injured hindlimb of immunodeficient mice.

PMID- 26222207
TI  - Thiamethoxam: Assessing flight activity of honeybees foraging on treated oilseed
      rape using radio frequency identification technology.
AB  - The present study was designed to assess homing behavior of bees foraging on
      winter oilseed rape grown from seed treated with thiamethoxam (as Cruiser OSR),
      with 1 field drilled with thiamethoxam-treated seed and 2 control fields drilled
      with fungicide-only-treated seed. Twelve honeybee colonies were used per
      treatment group, 4 each located at the field edge (on-field site), at
      approximately 500 m and 1000 m from the field. A total of nearly 300 newly
      emerged bees per colony were fitted (tagged) with Mic3 radio frequency
      identification (RFID) transponders and introduced into each of the 36 study
      hives. The RFID readers fitted to the entrances of the test colonies were used to
      monitor the activity of the tagged bees for the duration of the 5-wk flowering
      period of the crop. These activity data were analyzed to assess any impact on
      flight activity of bees foraging on the treated compared with untreated crops.
      Honeybees were seen to be actively foraging within all 3 treatment groups during
      the exposure period. The data for the more than 3000 RFID-tagged bees and more
      than 90 000 foraging flights monitored throughout the exposure phase for the
      study follow the same trends across the treatment and controls and at each of the
      3 apiary distances, indicating that there were no effects from foraging on the
      treated crop. Under the experimental conditions, there was no effect of foraging
      on thiamethoxam-treated oilseed rape on honeybee flight activity or on their
      ability to return to the hive.

PMID- 26222205
TI  - Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South
      Americans: A Descriptive, Multicenter, Cross-Sectional Study.
AB  - The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been
      investigated among different populations, and the results have indicated a low
      relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS)
      cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%
      27.5%) living in areas of low MS prevalence. South America (SA) was colonized by
      Europeans from the Iberian Peninsula, and their miscegenation with natives and
      Africans slaves resulted in significant racial mixing. The current study analyzed
      the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its
      population. A cross-sectional multicenter study was performed. Only individuals
      followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria
      were considered eligible. Patients' demographic, clinical and laboratory data
      were collected. In all, 1,917 individuals from 22 MS centers were included (73.7%
      female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main
      disease categories and their associated frequencies were MS (76.9%), NMO (11.8%),
      other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy
      (0.4%). Females predominated in all main categories. The white ethnicity also
      predominated, except in NMO. Except in ADEM, the disease onset occurred between
      20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in
      8.9%. The long-term morbidity after a mean disease time of 9.28+/-7.7 years was
      characterized by mild disability in all categories except in NMO, which was
      scored as moderate. Disease time among those with MS was positively correlated
      with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This
      correlation was not observed in people with NMO or those with other NMO spectrum
      disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting
      course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using
      indirect immunofluorescence (IIF) with a composite substrate of mouse tissues in
      200 NMOSD cases was positive in people with NMO (95/162; 58.6%), longitudinally
      extensive transverse myelitis (10/30; 33.3%) and bilateral or recurrent optic
      neuritis (8/8; 100%). No association of NMO-IgG antibody positivity was found
      with gender, age at onset, ethnicity, early or late onset forms, disease course,
      or long-term severe disability. The relative frequency of NMO among relapsing
      remitting MS (RRMS) + NMO cases in SA was 14.0%. Despite the high degree of
      miscegenation found in SA, MS affects three quarters of all patients with IIDD,
      mainly white young women who share similar clinical characteristics to those in
      Western populations in the northern hemisphere, with the exception of ethnicity;
      approximately one-third of all cases occur among non-white individuals. At the
      last assessment, the majority of RRMS patients showed mild disability, and the
      risk for secondary progression was significantly superior among those of African
      ethnicity. NMO comprises 11.8% of all IIDD cases in SA, affecting mostly young
      African-Brazilian women, evolving with a recurrent course and causing moderate or
      severe disability in both ethnic groups. The South-North gradient with increasing
      NMO and non-white individuals from Argentina, Paraguay, Brazil and Venezuela
      confirmed previous studies showing a higher frequency of NMO among non-white
      populations. 

PMID- 26222208
TI  - Hyaluronan synthase 3 (HAS3) overexpression downregulates MV3 melanoma cell
      proliferation, migration and adhesion.
AB  - Malignant skin melanoma is one of the most deadly human cancers. Extracellular
      matrix (ECM) influences the growth of malignant tumors by modulating tumor cells
      adhesion and migration. Hyaluronan is an essential component of the ECM, and its
      amount is altered in many tumors, suggesting an important role for hyaluronan in
      tumorigenesis. Nonetheless its role in melanomagenesis is not understood. In this
      study we produced a MV3 melanoma cell line with inducible expression of the
      hyaluronan synthase 3 (HAS3) and studied its effect on the behavior of the
      melanoma cells. HAS3 overexpression expanded the cell surface hyaluronan coat and
      decreased melanoma cell adhesion, migration and proliferation by cell cycle
      arrest at G1/G0. Melanoma cell migration was restored by removal of cell surface
      hyaluronan by Streptomyces hyaluronidase and by receptor blocking with hyaluronan
      oligosaccharides, while the effect on cell proliferation was receptor
      independent. Overexpression of HAS3 decreased ERK1/2 phosphorylation suggesting
      that inhibition of MAP-kinase signaling was responsible for these suppressive
      effects on the malignant phenotype of MV3 melanoma cells.

PMID- 26222209
TI  - Optoelectrical Molybdenum Disulfide (MoS2)--Ferroelectric Memories.
AB  - In this study, we fabricated and tested electronic and memory properties of field
      effect transistors (FETs) based on monolayer or few-layer molybdenum disulfide
      (MoS2) on a lead zirconium titanate (Pb(Zr,Ti)O3, PZT) substrate that was used as
      a gate dielectric. MoS2-PZT FETs exhibit a large hysteresis of electronic
      transport with high ON/OFF ratios. We demonstrate that the interplay of
      polarization and interfacial phenomena strongly affects the electronic behavior
      and memory characteristics of MoS2-PZT FETs. We further demonstrate that MoS2-PZT
      memories have a number of advantages and unique features compared to their
      graphene-based counterparts as well as commercial ferroelectric random-access
      memories (FeRAMs), such as nondestructive data readout, low operation voltage,
      wide memory window and the possibility to write and erase them both electrically
      and optically. This dual optoelectrical operation of these memories can simplify
      the device architecture and offer additional practical functionalities, such as
      an instant optical erase of large data arrays that is unavailable for many
      conventional memories. 

PMID- 26222210
TI  - Engineering Melanin Nanoparticles as an Efficient Drug-Delivery System for
      Imaging-Guided Chemotherapy.
AB  - In order to promote imaging-guided chemotherapy for preclinical and clinical
      applications, endogenous nanosystems with both contrast and drug-delivery
      properties are highly desired. Here, the simple use of melanin is first reported,
      and this biopolymer with good biocompatibility and biodegradability, binding
      ability to drugs and ions, and intrinsic photoacoustic properties, can serve as
      an efficient endogenous nanosystem for imaging-guided tumor chemotherapy in
      living mice. 

PMID- 26222211
TI  - An Aqueous Single Reactor Arc Discharge Process for the Synthesis of Graphene
      Nanospheres.
AB  - Using an aqueous single reactor arc discharge process with oil-in-water emulsions
      allows production of 2D multilayered graphenes (MLGs and 3D graphene-based
      crumpled/sphere-like particles with low levels of defects). The confinement
      forces to create 3D particles from 2D MLGs are estimated to be 2.5 MUN for
      crumpled particles and 70 MUN for spherical hollow particles. 

PMID- 26222212
TI  - Characteristics and Classification of Solid Radioactive Waste From the Front-End
      of the Uranium Fuel Cycle.
AB  - The proper classification of radioactive waste is the basis upon which to define
      its disposal method. In view of differences between waste containing artificial
      radionuclides and waste with naturally occurring radionuclides, the scientific
      definition of the properties of waste arising from the front end of the uranium
      fuel cycle (UF Waste) is the key to dispose of such waste. This paper is intended
      to introduce briefly the policy and practice to dispose of such waste in China
      and some foreign countries, explore how to solve the dilemma facing such waste,
      analyze in detail the compositions and properties of such waste, and finally put
      forward a new concept of classifying such waste as waste with naturally occurring
      radionuclides. 

PMID- 26222213
TI  - Natural Uranium Tissue Content of Three Caucasian Males.
AB  - Uranium content and concentrations were measured in the tissues of three
      Caucasian male whole body donors to the U.S. Transuranium and Uranium Registries
      with no known intake other than from natural environmental sources. Average total
      body uranium content in the three cases was 81.3 +/- 22.3 MUg, of which 37.2 +/-
      2.1 MUg (46%) was in the skeleton. The skeleton had a mean concentration of 3.79
      +/- 0.45 MUg U kg(-1) wet weight and 11.72 +/- 1.49 MUg U kg(-1) ash.
      Distribution was in bone volume and not predominately on bone surfaces. Soft
      tissue concentrations ranged over about an order of magnitude, averaging about
      0.5 MUg kg wet weight for all tissues except the thoracic lymph nodes, which
      averaged 32.3 times the mean for soft tissue of the three cases. Observed thyroid
      tissue concentrations were about an order of magnitude greater than the average
      soft tissue concentration in two of the three background cases, suggestive of a
      possible long-term depot in this organ. Kidney content of uranium averaged 0.38
      +/- 0.21 MUg for the three cases, an order of magnitude lower than the 7 MUg
      recommended for Reference Man. The lower content and concentration in the kidney
      do not support a significant long-term depot for uranium in that organ. Assuming
      equilibrium between intake and excretion, the tissue data suggest a transfer
      coefficient from blood to skeleton of 0.14 with a residence half-life in the
      skeleton of 4,950 d (13.56 y), significantly greater than the 1,500 d (4.1 y)
      half-time proposed by ICRP.

PMID- 26222214
TI  - Two Realistic Beagle Models for Dose Assessment.
AB  - Previously, the authors developed a series of eight realistic digital mouse and
      rat whole body phantoms based on NURBS technology to facilitate internal and
      external dose calculations in various species of rodents. In this paper, two body
      phantoms of adult beagles are described based on voxel images converted to NURBS
      models. Specific absorbed fractions for activity in 24 organs are presented in
      these models. CT images were acquired of an adult male and female beagle. The
      images were segmented, and the organs and structures were modeled using NURBS
      surfaces and polygon meshes. Each model was voxelized at a resolution of 0.75 *
      0.75 * 2 mm. The voxel versions were implemented in GEANT4 radiation transport
      codes to calculate specific absorbed fractions (SAFs) using internal photon and
      electron sources. Photon and electron SAFs were then calculated for relevant
      organs in both models. The SAFs for photons and electrons were compatible with
      results observed by others. Absorbed fractions for electrons for organ self
      irradiation were significantly less than 1.0 at energies above 0.5 MeV, as
      expected for many of these small-sized organs, and measurable cross irradiation
      was observed for many organ pairs for high-energy electrons (as would be emitted
      by nuclides like 32P, 90Y, or 188Re). The SAFs were used with standardized decay
      data to develop dose factors (DFs) for radiation dose calculations using the
      RADAR Method. These two new realistic models of male and female beagle dogs will
      be useful in radiation dosimetry calculations for external or internal simulated
      sources.

PMID- 26222215
TI  - Laser Safety Program Development at Texas A&M University--Issues and Challenges.
AB  - Implementing a laser safety program within a University setting encompassing a
      wide variety of Class 3b and Class 4 lasers with varied potential uses introduces
      many challenges. Texas A&M University (TAMU) currently has over 310 laser units
      that are registered with the Texas Department of State Health Services (TDSHS).
      One primary task in maintaining the laser registration is to have a program that
      identifies the regulatory responsibilities of the registrant. The Radiological
      Safety Staff, a part of Environmental Health and Safety (EHS), administers the
      use of both ionizing and non-ionizing radiation. The Radiological Safety Officer
      (RSO)/Laser Safety Officer (LSO) maintains the laser registration. This article
      outlines key elements that were put forth in the development and implementation
      of the laser safety program at TAMU. 

PMID- 26222216
TI  - Radiation Dose and Hazard Assessment of Potential Contamination Events During Use
      of 223Ra Dichloride in Radionuclide Therapy.
AB  - An analysis is presented of the possible dosimetric consequences of various
      potential contamination events involving 223Ra dichloride (Xofigo), the FDA
      approved therapeutic agent used in the treatment of bone metastases in patients
      with castration-resistant prostate cancer. Three exposure scenarios are
      considered: inhalation dose to an individual due to the hypothetical inhalation
      of 219Rn and its progeny assumed to be released into the air from a liquid spill
      on the floor, external dose from direct photon exposure of an individual assigned
      to clean up a spill, and skin dose to an individual should the liquid material
      come into contact with their skin. Doses from the first two scenarios were very
      small; 2.8 * 10(-3) mSv and 8.1 * 10(-4) mSv, respectively. Using extremely
      conservative assumptions, the skin dose was estimated to be 72 mSv; in a
      realistic scenario, this dose would likely be an order of magnitude or more
      lower. These doses are very small compared to regulatory limits, and good health
      physics practices likely to be employed in such incidents would lower them still
      further. The authors conclude that the medical use of Xofigo does not pose any
      significant radiation safety issue with respect to potential contamination
      events, even if multiple incidents might occur during the course of a year, since
      all worst-case potential contamination events considered in this study will not
      result in significant radiation exposures to workers.

PMID- 26222217
TI  - Comparative Modeling Analysis of the Hematopoiesis Dynamics in Mammals Exposed to
      Nonuniform and Uniform Acute Irradiation.
AB  - Biologically motivated mathematical models of the dynamics of the major
      hematopoietic lineages (the thrombopoietic, erythropoietic, granulopoietic, and
      lymphopoietic systems) in mammals (rodents) exposed to nonuniform acute
      irradiation are developed and thoroughly investigated. These models are based on
      earlier developed mathematical models, which are capable of predicting the
      dynamics of these systems in mammals (rodents) exposed to uniform acute/chronic
      irradiation. The developed models are the systems of nonlinear ordinary
      differential equations whose variables and constant parameters have clear
      biological meaning. It is found that these models are capable of reproducing a
      lesser depletion of the major hematopoietic lineages and faster recovery in
      rodents (rats, mice) after nonuniform acute irradiation than those after uniform
      acute irradiation at equal whole-body doses of such exposures. The nature of this
      phenomenon is elucidated in the framework of the models. Thorough comparative
      analysis of effects of nonuniform (partial) and uniform acute irradiation on the
      major hematopoietic lineages is performed. It is revealed that the lymphopoietic
      system is the most susceptible major hematopoietic lineage both to uniform and
      nonuniform (partial) acute irradiation. It is argued that the first-day level of
      the concentration of functional blood cells in this system (blood lymphocytes)
      after nonuniform (partial) acute irradiation can serve for early assessment of
      the risk of acute radiation syndrome. It is also shown that the modeling results
      on the first-day levels of the blood lymphocyte concentration after various
      partial acute exposures are in a very good agreement with the relevant
      experimental data. This agreement testifies to the applicability of the developed
      model of the lymphopoietic system to be used in the prognostic aims; in
      particular, for predicting the development of lymphocytopenia after partial acute
      irradiation. The modeling results imply that the prognostic use of a whole-body
      dose of nonuniform acute irradiation is not effective. The obtained results
      testify to the efficiency of the proposed dynamic modeling approach in the study
      of the effects of nonuniform acute irradiation on the major hematopoietic
      lineages and the validity of using developed models of the major hematopoietic
      lineages in the prediction of the effects of nonuniform acute irradiation on
      these systems in rodents and, after appropriate modification of the models, in
      humans. 

PMID- 26222218
TI  - Assessment of the Point-Source Method for Estimating Dose Rates to Members of the
      Public from Exposure to Patients with 131I Thyroid Treatment.
AB  - The U.S. Nuclear Regulatory Commission (USNRC) initiated a contract with Oak
      Ridge National Laboratory (ORNL) to calculate radiation dose rates to members of
      the public that may result from exposure to patients recently administered iodine
      131 (131I) as part of medical therapy. The main purpose was to compare dose rate
      estimates based on a point source and target with values derived from more
      realistic simulations of a human source and target. The latter simulations
      considered the time-dependent distribution of 131I in the patient and attenuation
      of emitted photons by the patient's tissues. The external dose rate estimates
      were derived using Monte Carlo methods and two representations of the Phantom
      with Movable Arms and Legs (PIMAL), previously developed by ORNL and the USNRC,
      to model the patient and a nearby member of the public. Dose rates to tissues and
      effective dose rates were calculated for distances ranging from 10 cm to 300 cm
      between the phantoms. Dose rates estimated from these simulations are compared to
      estimates based on the point-source method, as well as to results of previous
      studies that estimated exposure from 131I patients. The point-source method
      overestimates dose rates to members of the public in very close proximity to an
      131I patient but is a broadly accurate method of dose rate estimation at
      separation distances of 300 cm or more at times closer to administration.

PMID- 26222219
TI  - CCM-AMI, a Polyethylene Glycol Micelle with Amifostine, as an Acute Radiation
      Syndrome Protectant in C57BL/6 Mice.
AB  - Acute radiation syndrome results from radiation exposure, such as in accidental
      nuclear disasters. Safe and effective radioprotectants, mitigators, and treatment
      drugs must be developed as medical countermeasures against radiation exposure.
      Here, the authors evaluated CCM-Ami, a novel polyethylene glycol micelle
      encapsulated with amifostine, for its radioprotective properties after total-body
      irradiation from a 60Co source. Male C57BL/6 mice (6-8 wk old) were intravenously
      injected with 45 mg kg(-1) of CCM-Ami 90 min before exposure to 7.2 and 8.5 Gy
      irradiation at a dose rate of 0.04 Gy min(-1). Both survival benefit and
      hematopoietic protection were observed after prophylactic CCM-Ami administration
      when compared with the effects measured in excipient control and amifostine
      groups. Pharmacokinetic results showed that after the intravenous injection, the
      plasma concentration of WR-1065, the active form of amifostine, was higher in CCM
      Ami-treated mice than in amifostine-treated mice. These findings suggest that CCM
      Ami-mediated hematopoietic protection plays a key role in enhancing survival of
      mice exposed to radiation toxicity and thus indicate that CCM-Ami is a
      radioprotectant that can be used safely and effectively in nuclear disasters.

PMID- 26222220
TI  - Radiation Exposure of the Members of the Public from Patients Treated with 3.7
      GBq and 1.85 GBq of 131I--May We Simply Divide by 2?
AB  - In this work, the dose to the members of the public from two different 131I
      thyroid ablation patient groups (1.85 GBq and 3.7 GBq), whose a priori programmed
      hospitalization time is 48 h, is compared. The possibility of allocating half of
      the hospitalization time (24 h) for patients treated with 1.85 GBq is evaluated,
      having in mind the dose to the family members after patient release. The maximum
      dose rate at 1 m from the patient was measured at approximately 20 min, and 24,
      48, and 192 h after administration of 3.7 GBq to 70 patients and 1.85 GBq to 55
      patients. A triple exponential biological decay combined with physical decay was
      considered. Different weighting coefficients were applied to the squared
      residuals, allowing improved fitting and optimization of the calculation of the
      effective dose received by the public, E, by integration from 24 h or 48 h to
      infinite. Effective dose at 1 m from patients with 3.7 GBq after being released
      at 48 h is similar to the case of patients treated with 1.85 GBq after being
      released at 24 h. The average release dose rate at 24 h due to those patients is
      slightly higher than those administered with 3.7 GBq released at 48 h. However,
      no direct correspondence in the calculated dose to the members of the public was
      found, indicating that different dose rate release limits could be considered in
      both cases. These results show that it is safe, under the latest ICRP dose
      limits, to schedule a 24-h hospitalization time for patients administered with
      1.85 GBq.

PMID- 26222221
TI  - A Review of Joseph J. Mangano's Study on the Variation in Thyroid Cancer
      Incidence.
AB  - Researchers have attempted to link incidences of papillary thyroid cancer with
      radioiodine releases from nuclear power plants. Thyroid cancer detection rates
      are examined together with overall population exposure to ionizing radiation and
      actual radioiodine releases from the Indian Point Energy Center to determine if a
      causal relationship exists. A critical review of the statistical analyses used in
      previous papers is then presented. 

PMID- 26222225
TI  - Factors associated with experiences and attitudes of healthcare professionals
      towards family-witnessed resuscitation: a cross-sectional study.
AB  - AIMS: To examine factors associated with healthcare professionals' experiences
      and attitudes towards adult family-witnessed resuscitation in the emergency and
      intensive care units. BACKGROUND: Family-witnessed resuscitation offers the
      option for patients' families to be present during in-hospital resuscitation. It
      is important to understand healthcare professionals' views about this practice to
      determine why, despite its benefits and general recommendation, this practice has
      not been widely implemented. DESIGN: A descriptive, correlational, cross
      sectional survey. METHODS: A total of 390 Finnish and Polish Registered Nurses
      and physicians from six university hospitals took part in the study. A structured
      questionnaire that examined nurses' and physicians' experiences and attitudes was
      used. Data, collected between July-December 2013, were analysed with descriptive
      statistics, logistic and multiple linear regression analyses. RESULTS: The
      results indicated that healthcare professionals are not well experienced in
      family-witnessed resuscitation. The general attitude towards this practice is
      somewhat negative. Physicians seem more confident about overcoming process
      related barriers than nurses. Having previous positive experiences of family
      witnessed resuscitation was associated with a more positive attitude towards this
      practice. Consequently a previous negative experience was associated with more
      negative attitudes. CONCLUSION: Family-witnessed resuscitation awareness should
      be increased in daily clinical practice. It is important to find a way to improve
      experiences and attitudes of healthcare professionals related to this phenomenon.
      Furthermore, developing local guidelines and multidisciplinary training plans is
      needed to respond to the needs of patients and their families.

PMID- 26222226
TI  - Ultra-processed foods have the worst nutrient profile, yet they are the most
      available packaged products in a sample of New Zealand supermarkets.
AB  - OBJECTIVE: To examine the availability of packaged food products in New Zealand
      supermarkets by level of industrial processing, nutrient profiling score (NPSC),
      price (energy, unit and serving costs) and brand variety. DESIGN: Secondary
      analysis of cross-sectional survey data on packaged supermarket food and non
      alcoholic beverages. Products were classified according to level of industrial
      processing (minimally, culinary and ultra-processed) and their NPSC. SETTING:
      Packaged foods available in four major supermarkets in Auckland, New Zealand.
      SUBJECTS: Packaged supermarket food products for the years 2011 and 2013.
      RESULTS: The majority (84% in 2011 and 83% in 2013) of packaged foods were
      classified as ultra-processed. A significant positive association was found
      between the level of industrial processing and NPSC, i.e., ultra-processed foods
      had a worse nutrient profile (NPSC=11.63) than culinary processed foods
      (NPSC=7.95), which in turn had a worse nutrient profile than minimally processed
      foods (NPSC=3.27), P<0.001. No clear associations were observed between the three
      price measures and level of processing. The study observed many variations of
      virtually the same product. The ten largest food manufacturers produced 35% of
      all packaged foods available. CONCLUSIONS: In New Zealand supermarkets, ultra
      processed foods comprise the largest proportion of packaged foods and are less
      healthy than less processed foods. The lack of significant price difference
      between ultra- and less processed foods suggests ultra-processed foods might
      provide time-poor consumers with more value for money. These findings highlight
      the need to improve the supermarket food supply by reducing numbers of ultra
      processed foods and by reformulating products to improve their nutritional
      profile.

PMID- 26222227
TI  - A self-regulatory approach to understanding boredom proneness.
AB  - We investigated the relationship between self-regulation and two types of boredom
      proneness (perceived lack of internal stimulation, perceived lack of external
      stimulation) using a variety of measures of self-regulation. These included a
      general measure of self-control, measures of both regulatory focus (i.e.,
      promotion or a sensitivity to gains/non-gains vs. prevention or a sensitivity to
      losses/non-losses) and regulatory mode (i.e., assessment or the tendency to
      compare means and goals vs. locomotion or the tendency to initiate and maintain
      commitment to action), and measures of cognitive flexibility (i.e., a perceived
      sense of control and the tendency to seek alternative solutions). Results
      identified a unique set of factors related to each boredom proneness component.
      Trait self-control and prevention focus were associated with lower boredom
      propensity due to a lack of external stimulation. Locomotion and the tendency to
      seek alternatives were associated with lower boredom propensity due to a lack of
      internal stimulation. These findings suggest that effective goal pursuit is
      associated with reduced likelihood of experiencing boredom.

PMID- 26222229
TI  - Reported shoes size during GH therapy: is foot overgrowth a myth or reality?
AB  - OBJECTIVES: To describe population reference values for shoes size, and to
      identify possible disproportional foot growth during GH therapy. MATERIALS AND
      METHODS: Construction of percentile chart based on 3,651 controls (male: 1,838;
      female: 1,813). The GH treated group included 13 children with idiopathic short
      stature (ISS) and 50 children with normal height, but with height prediction
      below their target height; male: 26 and female: 37 mean +/- SD age 13.3 +/- 1.9
      and 12.9 +/- 1.5 years, respectively. GH (0.05 mg/kg/day) was used for 3.2 +/-
      1.6 years, ranging from 1.0-10.3 years. Height expressed as SDS, target height
      (TH) SDS, self-reported shoes size and target shoes size (TSS) SDS were recorded.
      RESULTS: Reference values were established showed as a foot SDS calculator
      available online at www.clinicalcaselearning.com/v2. Definitive shoes size was
      attained in controls at mean age of 13y in girls and 14y in boys (average values
      37 and 40, respectively). In the study group, shoes size was -0.15 +/- 0.9 and 
      0.02 +/- 1.3 SDS, with target feet of 0.08 +/- 0.8 and -0.27 +/- 0.7 SDS in males
      and females, respectively. There was a significant positive correlation between
      shoes size and familial TSS, between shoes size and height and between TSS and
      TH. There was no correlation between duration of GH treatment and shoes size. Our
      data suggest that during long-term treatment with GH, patients maintain
      proportional growth in shoes size and height, and the expected correlation with
      the familial target. CONCLUSIONS: We conclude that there is no excessive increase
      in the size of foot as estimated by the size of shoes in individuals under long
      term GH therapy.

PMID- 26222228
TI  - Alkaline phosphatase protects against renal inflammation through
      dephosphorylation of lipopolysaccharide and adenosine triphosphate.
AB  - BACKGROUND AND PURPOSE: Recently, two phase-II trials demonstrated improved renal
      function in critically ill patients with sepsis-associated acute kidney injury
      treated with the enzyme alkaline phosphatase. Here, we elucidated the dual active
      effect on renal protection of alkaline phosphatase. EXPERIMENTAL APPROACH: The
      effect of human recombinant alkaline phosphatase (recAP) on LPS-induced renal
      injury was studied in Sprague-Dawley rats. Renal function was assessed by
      transcutaneous measurement of FITC-sinistrin elimination in freely moving, awake
      rats. The mechanism of action of recAP was further investigated in vitro using
      conditionally immortalized human proximal tubular epithelial cells (ciPTEC). KEY
      RESULTS: In vivo, LPS administration significantly prolonged FITC-sinistrin half
      life and increased fractional urea excretion, which was prevented by recAP co
      administration. Moreover, recAP prevented LPS-induced increase in proximal tubule
      injury marker, kidney injury molecule-1 expression and excretion. In vitro, LPS
      induced production of TNF-alpha, IL-6 and IL-8 was significantly attenuated by
      recAP. This effect was linked to dephosphorylation, as enzymatically inactive
      recAP had no effect on LPS-induced cytokine production. RecAP-mediated protection
      resulted in increased adenosine levels through dephosphorylation of LPS-induced
      extracellular ADP and ATP. Also, recAP attenuated LPS-induced increased
      expression of adenosine A2A receptor. However, the A2A receptor antagonist ZM
      241385 did not diminish the effects of recAP. CONCLUSIONS AND IMPLICATIONS: These
      results indicate that the ability of recAP to reduce renal inflammation may
      account for the beneficial effect observed in septic acute kidney injury
      patients, and that dephosphorylation of ATP and LPS are responsible for this
      protective effect.

PMID- 26222230
TI  - Is radioactive iodine- 131 treatment related to the occurrence of non-synchronous
      second primary malignancy in patients with differentiated thyroid cancer?
AB  - OBJECTIVE: Much controversy relates to the risk of non-synchronous second primary
      malignancies (NSSPM) after radioactive iodine treatment (RAI-131) in
      differentiated thyroid cancer (DTC) patients. This study evaluated the
      relationship between RAI-131 and NSSPM in DTC survivors with long-term follow-up.
      MATERIALS AND METHODS: Retrospective analysis of 413 DTC cases was performed; 252
      received RAI-131 and 161 were treated with thyroidectomy alone. Exclusion
      criteria were: prior or synchronous non-thyroidal malignancies (within the first
      year), familial syndromes associated to multiple neoplasms, ionizing radiation
      exposure or second tumors with unknown histopathology. RESULTS: During a mean
      follow-up of 11.0 +/- 7.5 years, 17 (4.1%) patients developed solid NSSPM.
      Patients with NSSPM were older than those without (p = 0.02). RAI-131 and I-131
      cumulative activity were similar in patients with and without NSSPM (p = 0.18 and
      p = 0.78, respectively). Incidence of NSSPM was 5.2% in patients with RAI-131
      treatment and 2.5% in those without RAI-131 (p = 0.18). Using multivariate
      analysis, RAI-131 was not significantly associated with NSSPM occurrence (p =
      0.35); age was the only independent predictor (p = 0.04). Under log rank
      statistical analysis, after 10 years of follow-up, it was observed a tendency of
      lower NSSPM-free survival among patients that received RAI-131 treatment (0.96 vs
      . 0.87; p = 0.06), what was not affected by age at DTC diagnosis. CONCLUSION: In
      our cohort of DTC survivors, with a long-term follow-up period, RAI-131 treatment
      and I-131 cumulative dose were not significantly associated with NSSPM
      occurrence. A tendency of premature NSSPM occurrence among patients treated with
      RAI-131 was observed, suggesting an anticipating oncogenic effect by interaction
      with other risk factors.

PMID- 26222231
TI  - Does low serum TSH within the normal range have negative impact on physical
      exercise capacity and quality of life of healthy elderly people?
AB  - OBJECTIVE: Investigate the differences in cardiopulmonary (CP) capacity and
      Quality of Life (QOL) between healthy elderly (>= 65 years) with different TSH
      levels (< 1.0 and >= 1.0 MUIU/mL) both within the normal range. Also, evaluate
      the effects of TSH elevation on CP test and QOL, by administering methimazole to
      subjects with initial lower-normal TSH, in order to elevate it to superior-normal
      limit. MATERIALS AND METHODS: Initially, a cross-sectional study was performed to
      compare CP capacity at peak exercise and QOL (using WHOQOL-OLD questionnaire)
      between healthy seniors (age >= 65 years) with TSH < 1.0 MUIU/mL vs. TSH >=1.0
      MUIU/mL. In the second phase, participants with TSH < 1.0 MUIU/mL were included
      in a non-controlled-prospective-interventional study to investigate the effect of
      TSH elevation, using methimazole, on QOL and CP capacity at peak exercise.
      RESULTS: From 89 elderly evaluated, 75 had TSH >= 1 MUIU/mL and 14 TSH < 1
      MUIU/mL. The two groups had similar basal clinical characteristics. No difference
      in WHOQOL-OLD scores was observed between groups and they did not differ in terms
      of CP function at peak exercise. QOL and CP variables were not correlated with
      TSH levels. Twelve of 14 participants with TSH < 1.0 MUIU/mL entered in the
      prospective study. After one year, no significant differences in clinical
      caracteristics, QOL, and CP variables were detected in paired analysis before and
      after methimazole intervention. CONCLUSIONS: We found no differences in CP
      capacity and QOL between health elderly with different TSH levels within normal
      range and no impact after one year of methimazole treatment. More prospective
      controlled-randomized studies are necessary to confirm or not the possible harm
      effect in normal low TSH.

PMID- 26222232
TI  - Thyroid surgery performed on an overnight basis: a 17 years of experience.
AB  - OBJECTIVE: This study aimed to evaluate the results of thyroid surgeries with
      hospitalization periods shorter than 18 hours performed in a surgical
      endocrinology service, correlating these results with type of procedure, the
      definitive diagnosis and complications associated with the procedure. SUBJECTS
      AND METHODS: The procedures performed, complications associated, hospitalization
      period, and relationships among these variables were assessed in consecutive
      patients subjected to different types of thyroid surgeries from January 1997 to
      March 2014 by the same group of surgeons. Data were analyzed by frequency, and
      the associations between the hospitalization period and other variables were
      analyzed using the Pearson chi-square test and Fisher's exact test, using a
      multiple comparisons test with Bonferroni correction. RESULTS: Among the 3,411
      surgeries performed, 799 of them were malignant neoplasia, 2,505 were benign
      tumors and 107 were Graves' disease. The following procedures were performed:
      total thyroidectomy (1597 patients); total thyroidectomy with neck exploration
      (369 patients); lobectomy plus isthmectomy (1084 patients); total thyroidectomy
      complementation (145 patients); total thyroidectomy with neck dissection (84
      patients); modified radical total thyroidectomy (13 patients); nodulectomy (11
      patients); unresectable (9 patients); central neck dissection (48 patients);
      lateral neck dissection (38 patients); and others (13 patients). The following
      surgical complications, characteristic of the procedure: hemorrhage in 41 (1.2%)
      patients, hypoparathyroidism in 10 (0.3%) patients and recurrent laryngeal nerve
      (RLN) injury in 23 (0.7%) patients. Hospitalization shorter than 18 hours was
      observed in 97% of patients. CONCLUSION: Thyroid surgery can be safely performed
      in virtually all patients on an overnight basis in specialized services.

PMID- 26222233
TI  - Screening for primary aldosteronism in an argentinian population: a multicenter
      prospective study.
AB  - OBJECTIVES: Primary aldosteronism (PA) is characterized by the autonomous
      overproduction of aldosterone. Its prevalence has increased since the use of the
      aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this
      study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off
      values (COV) and their diagnostic concordance (DC%) in the screening for PA in an
      Argentinian population.Design multicenter prospective study. SUBJECTS AND
      METHODS: We studied 353 subjects (104 controls and 249 hypertensive patients).
      Serum aldosterone, PRA and ARR were determined. In 220 randomly selected
      subjects, 160 hypertensive patients and 60 controls, plasma renin concentration
      (PRC) was simultaneously measured and ARC was determined. RESULTS: According to
      the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for
      ARC, with ALD >= 15 ng/dL. In 31/249 hypertensive patients, ARR was >= 36. PA
      diagnosis was established in 8/31 patients (23/31 patients did not complete
      confirmatory tests). DC% between ARR and ARC was calculated. A significant
      correlation between ARR and ARC (r = 0.742; p < 0.0001) was found only with PRA >
      0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was
      79.1%, respectively. CONCLUSION: This first Argentinian multicenter study
      determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR >= 36 in the
      hypertensive group, we confirmed PA in a higher percentage of patients than the
      previously reported one in our population. As for ARC, further studies are needed
      for its clinical application, since DC% is acceptable only for medium range renin
      values.

PMID- 26222243
TI  - A cobalt oxyhydroxide-modified upconversion nanosystem for sensitive fluorescence
      sensing of ascorbic acid in human plasma.
AB  - Ascorbic acid (AA), a potent antioxidant readily scavenging reactive species, is
      a crucial micronutrient involved in many biochemical processes. Here, we have
      developed a cobalt oxyhydroxide (CoOOH)-modified upconversion nanosystem for
      fluorescence sensing of AA activity in human plasma. The nanosystem consists of
      upconversion nanoparticles (UCNPs) NaYF4:30% Yb,0.5% Tm@NaYF4, which serve as
      energy donors, and CoOOH nanoflakes formed on the surface of UCNPs, which act as
      efficient energy acceptors. The fluorescence resonance energy transfer (FRET)
      process from the UCNPs to the absorbance of the CoOOH nanoflakes occurs in the
      nanosystem. The AA-mediated specific redox reaction reduces CoOOH into Co(2+),
      leading to the inhibition of FRET, and resulting in the recovery of upconversion
      emission spectra. On the basis of these features, the nanosystem can be used for
      sensing AA activity with sensitivity and selectivity. Moreover, due to the
      minimizing background interference provided by UCNPs, the nanosystem has been
      applied to monitoring AA levels in human plasma sample with satisfactory results.
      The proposed approach may potentially provide an analytical platform for research
      and clinical diagnosis of AA related diseases. 

PMID- 26222244
TI  - The role of methotrexate and low-dose prednisolone on adiponectine levels and
      insulin resistance in patients with rheumatoid arthritis naive to disease
      modifying antirheumatic drugs.
AB  - AIM: Insulin resistance (IR) plays an important role in the development of
      cardiovascular events in rheumatoid arthritis (RA) patients. Adiponectin
      influences insulin sensitivity but its impact on IR in RA patients remains
      unclear. The present study aims to investigate the role of methotrexate (MTX) and
      low doses of prednisolone (LDP) on IR and adiponectin levels in RA patients who
      are naive to disease-modifying antirheumatic drugs (DMARDs), as well as
      determining the relationship between disease activity, acute phase response, IR
      and adiponectin levels in patients with RA. METHODS: Sixty-five RA patients naive
      to DMARDs and prednisolone were involved in this study. The medication for RA
      patients was standardized for MTX and prednisolone. Body mass index, acute phase
      response reactants, 28-joint-count disease activity score, fasting blood glucose,
      serum cholesterol levels, insulin levels and adiponectin levels were measured in
      all RA patients both at the baseline and 3 months after the onset of the study.
      RESULTS: Adiponectin levels in the third month of the therapy with MTX and LDP
      were significantly increased in patients with RA (P = 0.03). Insulin resistance
      tended to decrease in the third month of the treatment, which achieved no
      statistical significance. CONCLUSION: Increased levels of adiponectin due to MTX
      and LDP could be related to the decrease in homeostasis model assessment insulin
      resistance (HOMA-IR) in RA patients. This, in turn, could prove advantageous for
      cardiovascular conditions in RA.

PMID- 26222245
TI  - External cephalic version for breech presentation before term.
AB  - BACKGROUND: External cephalic version (ECV) of the breech fetus at term (after 37
      weeks) has been shown to be effective in reducing the number of breech
      presentations and caesarean sections, but the rates of success are relatively
      low. This review examines studies initiating ECV prior to term (before 37 weeks'
      gestation). OBJECTIVES: To assess the effectiveness of a policy of beginning ECV
      before term (before 37 weeks' gestation) for breech presentation on fetal
      presentation at birth, method of delivery, and the rate of preterm birth,
      perinatal morbidity, stillbirth or neonatal mortality. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March
      2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) of ECV attempted before term (37 weeks' gestation) or
      commenced before term, compared with a control group of women (in breech
      presentation) in which either no ECV attempted or ECV was attempted at term.
      Cluster-randomised trials were eligible for inclusion but none were identified.
      Quasi-RCTs or studies using a cross-over design were not eligible for inclusion.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials
      for inclusion and risk of bias, extracted data and checked for accuracy. Studies
      were assessed for risk of bias and for important outcomes the overall quality of
      the evidence was assessed using the GRADE approach. MAIN RESULTS: Five studies
      are included (2187 women). It was not possible for the intervention to be
      blinded, and it is not clear what impact lack of blinding would have on the
      outcomes reported. For other 'Risk of bias' domains studies were either at low or
      unclear risk of bias.One study reported on ECV that was undertaken and completed
      before 37 weeks' gestation compared with no ECV. No difference was found in the
      rate of non-cephalic presentation at birth (risk ratio (RR) 1.04, 95% confidence
      interval (CI) 0.64 to 1.69; participants = 102). One study reported on a policy
      of ECV that was initiated before term (33 weeks) and up until 40 weeks' gestation
      and which could be repeated up until delivery compared with no ECV. This study
      showed a decrease in the rate of non-cephalic presentation at birth (RR 0.59, 95%
      CI 0.45 to 0.77; participants = 179).Three studies reported on ECV started at
      between 34 to 35 weeks' gestation compared with beginning at 37 to 38 weeks'
      gestation. Pooled results suggested that early ECV reduced the risk of non
      cephalic presentation at birth (RR 0.81, 95% CI 0.74 to 0.90; participants =
      1906; studies = three; I2 = 0%, evidence graded high quality), failure to achieve
      vaginal cephalic birth (RR 0.90, 95% CI 0.83 to 0.97; participants = 1888;
      studies = three; I2 = 0%, evidence graded high quality), and vaginal breech
      delivery (RR 0.44, 95% CI 0.25 to 0.78; participants = 1888; studies = three; I2
      = 0%, evidence graded high quality). The difference between groups for risk of
      caesarean was not statistically significant (RR 0.92, 95% CI 0.85 to 1.00;
      participants = 1888; studies = three; I2 = 0%, evidence graded high quality).
      There was evidence that risk of preterm labour was increased with early ECV
      compared with ECV after 37 weeks (6.6% in the ECV group and 4.3% for controls)
      (RR 1.51, 95% CI 1.03 to 2.21; participants = 1888; studies = three; I2 = 0%,
      evidence graded high quality). There was no clear difference between groups for
      low infant Apgar score at five minutes or perinatal death (stillbirth plus
      neonatal mortality up to seven days) (evidence graded as low quality for both
      outcomes). AUTHORS' CONCLUSIONS: Compared with no ECV attempt, ECV commenced
      before term reduces non-cephalic presentation at birth. Compared with ECV at
      term, beginning ECV at between 34 to 35 weeks may have some benefit in terms of
      decreasing the rate of non-cephalic presentation, and risk of vaginal breech
      birth. However, early ECV may increase risk of late preterm birth, and it is
      important that any future research reports infant morbidity outcomes. Results of
      the review suggest that there is a need for careful discussion with women about
      the timing of the ECV procedure so that they can make informed decisions.

PMID- 26222246
TI  - Interventions for pain with intrauterine device insertion.
AB  - BACKGROUND: Fear of pain during insertion of intrauterine contraception (IUC) is
      a barrier to use of this method. IUC includes copper-containing intrauterine
      devices and levonorgestrel-releasing intrauterine systems. Interventions for pain
      control during IUC insertion include non-steroidal anti-inflammatory drugs
      (NSAIDs), local cervical anesthetics, and cervical ripening agents such as
      misoprostol. OBJECTIVES: To review randomized controlled trials (RCTs) of
      interventions for reducing IUC insertion-related pain SEARCH METHODS: We searched
      for trials in CENTRAL, MEDLINE, EMBASE, POPLINE, ClinicalTrials.gov, and ICTRP.
      The most recent search was 22 June 2015. We examined reference lists of pertinent
      articles. For the initial review, we wrote to investigators to find other
      published or unpublished trials. SELECTION CRITERIA: We included RCTs that
      evaluated an intervention for preventing IUC insertion-related pain. The
      comparison could have been a placebo, no intervention, or another active
      intervention. The primary outcomes were self-reported pain at tenaculum
      placement, during IUC insertion, and after IUC insertion (up to six hours). DATA
      COLLECTION AND ANALYSIS: Two authors extracted data from eligible trials. For
      dichotomous variables, we calculated the Mantel-Haenszel odds ratio (OR) with 95%
      confidence interval (CI). For continuous variables, we computed the mean
      difference (MD) with 95% CI. In meta-analysis of trials with different
      measurement scales, we used the standardized mean difference (SMD). MAIN RESULTS:
      We included 33 trials with 5710 participants total; 29 were published from 2010
      to 2015. Studies examined lidocaine, misoprostol, NSAIDs, and other
      interventions. Here we synthesize results from trials with sufficient outcome
      data and moderate- or high-quality evidence.For lidocaine, meta-analysis showed
      topical 2% gel had no effect on pain at tenaculum placement (two trials) or on
      pain during IUC insertion (three trials). Other formulations were effective
      compared with placebo in individual trials. Mean score for IUC-insertion pain was
      lower with lidocaine and prilocaine cream (MD -1.96, 95% CI -3.00 to -0.92).
      Among nulliparous women, topical 4% formulation showed lower scores for IUC
      insertion pain assessed within 10 minutes (MD -15.90, 95% CI -22.77 to -9.03) and
      at 30 minutes later (MD -11.10, 95% CI -19.05 to -3.15). Among parous women, IUC
      insertion pain was lower with 10% spray (median 1.00 versus 3.00). Compared with
      no intervention, pain at tenaculum placement was lower with 1% paracervical block
      (median 12 versus 28).For misoprostol, meta-analysis showed a higher mean score
      for IUC insertion compared with placebo (SMD 0.27, 95% CI 0.07 to 0.46; four
      studies). In meta-analysis, cramping was more likely with misoprostol (OR 2.64,
      95% CI 1.46 to 4.76; four studies). A trial with nulliparous women found a higher
      score for IUC-insertion pain with misoprostol (median 46 versus 34). Pain before
      leaving the clinic was higher for misoprostol in two trials with nulliparous
      women (MD 7.60, 95% CI 6.48 to 8.72; medians 35.5 versus 20.5). In one trial with
      nulliparous women, moderate or severe pain at IUC insertion was less likely with
      misoprostol (OR 0.30, 95% CI 0.16 to 0.55). In the same trial, the misoprostol
      group was more likely to rate the experience favorably. Within two trials of
      misoprostol plus diclofenac, shivering, headache, or abdominal pain were more
      likely with misoprostol. Participants had no vaginal delivery. One trial showed
      the misoprostol group less likely to choose or recommend the treatment.Among
      multiparous women, mean score for IUC-insertion pain was lower for tramadol 50 mg
      versus naproxen 550 mg (MD -0.63, 95% CI -0.94 to -0.32) and for naproxen versus
      placebo (MD -1.94, 95% CI -2.35 to -1.53). The naproxen group was less likely
      than the placebo group to report the insertion experience as unpleasant and not
      want the medication in the future. An older trial showed repeated doses of
      naproxen 300 mg led to lower pain scores at one hour (MD -1.04, 95% CI -1.67 to 
      0.41) and two hours (MD -0.98, 95% CI -1.64 to -0.32) after insertion. Most women
      were nulliparous and also had lidocaine paracervical block. AUTHORS' CONCLUSIONS:
      Nearly all trials used modern IUC. Most effectiveness evidence was of moderate
      quality, having come from single trials. Lidocaine 2% gel, misoprostol, and most
      NSAIDs did not help reduce pain. Some lidocaine formulations, tramadol, and
      naproxen had some effect on reducing IUC insertion-related pain in specific
      groups. The ineffective interventions do not need further research.

PMID- 26222247
TI  - The use of propofol for procedural sedation in emergency departments.
AB  - BACKGROUND: There is increasing evidence that propofol is efficacious and safe
      for procedural sedation (PS) in the emergency department (ED) setting. However,
      propofol has a narrow therapeutic window and lacks of a reversal agent. The aim
      of this review was to cohere the evidence base regarding the efficacy and safety
      profile of propofol when used in the ED setting for PS. OBJECTIVES: To identify
      and evaluate all randomized controlled trials (RCTs) comparing propofol with
      alternative drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in
      the ED setting for PS. SEARCH METHODS: We searched the Cochrane Central Register
      of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE
      (1950 to September week 2 2013) and EMBASE (1980 to week 2 2013). We searched the
      Current Controlled Trials metaRegister of Clinical Trials (compiled by Current
      Science) (September 2013). We checked the reference lists of trials and contacted
      trial authors. We imposed no language restriction. We re-ran the search in
      February 2015. We will deal with the one study awaiting classification when we
      update the review. SELECTION CRITERIA: RCTs comparing propofol to alternative
      drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in the ED
      setting for PS in participants of all ages. DATA COLLECTION AND ANALYSIS: Two
      authors independently performed data extraction. Two authors performed trial
      quality assessment. We used mean difference (MD), odds ratio (OR) and 95%
      confidence intervals (CI) to measure effect sizes. Two authors independently
      assessed and rated the methodological quality of each trial using The Cochrane
      Collaboration tool for assessing risk of bias. MAIN RESULTS: Ten studies (813
      participants) met the inclusion criteria. Two studies only included participants
      18 years and younger; six studies only included participants 18 years and older;
      one study included participants between 16 and 65 years of age and one study
      included only adults but did not specify the age range. Eight of the included
      studies had a high risk of bias. The included studies were clinically
      heterogeneous. We undertook no meta-analysis.The primary outcome measures of this
      review were: adverse effects (as defined by the study authors) and participant
      satisfaction (as defined by the study authors). In one study comparing
      propofol/fentanyl with ketamine/midazolam, delayed adverse reactions (nightmares
      and behavioural change) were noted in 10% of the ketamine/midazolam group and
      none in the propofol/fentanyl group. Seven individual studies reported no
      evidence of a difference in adverse effects between intravenous propofol, with
      and without adjunctive analgesic agents, and alternative interventions. Three
      individual studies reported no evidence of a difference in pain at the injection
      site between intravenous propofol and alternative interventions. Four individual
      studies reported no evidence of a difference in participant satisfaction between
      intravenous propofol, with and without adjunctive analgesic agents, and
      alternative interventions (ketamine, etomidate, midazolam). All the studies
      employed propofol without the use of an adjunctive analgesic and all, except one,
      were small (fewer than 100 participants) studies. The quality of evidence for the
      adverse effects and participant satisfaction outcomes was very low.Nine included
      studies (eight comparisons) reported all the secondary outcome measures of the
      review except mortality. It was not possible to pool the results of the included
      studies for any of the secondary outcome measures because the comparator
      interventions were different and the measures were reported in different ways.
      Seven individual studies reported no evidence of difference in incidence of
      hypoxia between intravenous propofol, with and without adjunctive analgesic
      agents, and alternative interventions. AUTHORS' CONCLUSIONS: No firm conclusions
      can be drawn concerning the comparative effects of administering intravenous
      propofol, with or without an adjunctive analgesic agent, with alternative
      interventions in participants undergoing PS in the ED setting on adverse effects
      (including pain at the injection site) and participant satisfaction. The review
      was limited because no two included studies employed the same comparator
      interventions, and because the number of participants in eight of the included
      studies were small (fewer than 100 participants).

PMID- 26222248
TI  - WITHDRAWN: Targeting intensive glycaemic control versus targeting conventional
      glycaemic control for type 2 diabetes mellitus.

PMID- 26222249
TI  - WITHDRAWN: Sulphonylurea monotherapy for patients with type 2 diabetes mellitus.

PMID- 26222250
TI  - Surgical versus nonsurgical interventions for flail chest.
AB  - BACKGROUND: Thoracic trauma (TT) is common among people with multiple traumatic
      injuries. One of the injuries caused by TT is the loss of thoracic stability
      resulting from multiple fractures of the rib cage, otherwise known as flail chest
      (FC). A person with FC can be treated conservatively with orotracheal intubation
      and mechanical ventilation (internal pneumatic stabilization) but may also
      undergo surgery to fix the costal fractures. OBJECTIVES: To evaluate the
      effectiveness and safety of surgical stabilization compared with clinical
      management for people with FC. SEARCH METHODS: We ran the search on the 12 May
      2014. We searched the Cochrane Injuries Group's Specialised Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library),
      MEDLINE (OvidSP), EMBASE Classic and EMBASE (OvidSP), CINAHL Plus (EBSCO), ISI
      WOS (SCI-EXPANDED, SSCI, CPCI-S, and CPSI-SSH), and clinical trials registers. We
      also screened reference lists and contacted experts. SELECTION CRITERIA:
      Randomized controlled trials of surgical versus nonsurgical treatment for people
      diagnosed with FC. DATA COLLECTION AND ANALYSIS: Two review authors selected
      relevant trials, assessed their risk of bias, and extracted data. MAIN RESULTS:
      We included three studies that involved 123 people. The methods used for blinding
      the participants and researchers to the treatment group were not reported, but as
      the comparison is surgical treatment with medical treatment this bias is hard to
      avoid. There was no description of concealment of the randomization sequence in
      two studies.All three studies reported on mortality, and deaths occurred in two
      studies. There was no clear evidence of a difference in mortality between
      treatment groups (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.13 to
      2.42); however, the analysis was underpowered to detect a difference between
      groups. Out of the 123 people randomized and treated, six people died; the causes
      of death were pneumonia, pulmonary embolism, mediastinitis, and septic
      shock.Among people randomized to surgery, there were reductions in pneumonia (RR
      0.36, 95% 0.15 to 0.85; three studies, 123 participants), chest deformity (RR
      0.13, 95% CI 0.03 to 0.67; two studies, 86 participants), and tracheostomy (RR
      0.38, 95% CI 0.14 to 1.02; two studies, 83 participants). Duration of mechanical
      ventilation, length of intensive care unit stay (ICU), and length of hospital
      stay were measured in the three studies. Due to differences in reporting, we
      could not combine the results and have listed them separately. Chest pain, chest
      tightness, bodily pain, and adverse effects were each measured in one study.
      AUTHORS' CONCLUSIONS: There was some evidence from three small studies that
      showed surgical treatment was preferable to nonsurgical management in reducing
      pneumonia, chest deformity, tracheostomy, duration of mechanical ventilation, and
      length of ICU stay. Further well-designed studies with a sufficient sample size
      are required to confirm these results and to detect possible surgical effects on
      mortality.

PMID- 26222251
TI  - Endoscopic third ventriculostomy (ETV) for idiopathic normal pressure
      hydrocephalus (iNPH).
AB  - BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a type of
      communicating hydrocephalus also known as non-obstructive hydrocephalus. This
      type of hydrocephalus is caused by impaired cerebrospinal fluid reabsorption
      without any obstruction in the ventricular system and is associated with normal
      cerebrospinal fluid pressure. It is characterised clinically by gait disturbance,
      cognitive dysfunction, and urinary incontinence (known as the Hakim-Adams triad).
      The exact cause of iNPH is unknown. It may be managed conservatively or treated
      surgically by inserting a ventriculoperitoneal (VP) or ventriculoatrial (VA)
      shunt. However, a substantial number of patients do not respond well to surgical
      treatment, complication rates are high and there is often a need for further
      surgery. Endoscopic third ventriculostomy (ETV) is an alternative surgical
      intervention. It has been suggested that ETV may lead to better outcomes,
      including fewer complications. OBJECTIVES: To determine the effectiveness of ETV
      for treatment of patients with iNPH compared to conservative therapy, or shunting
      of CSF using VP or VA shunts.To assess the perioperative and postoperative
      complication rates in patients with iNPH after ETV compared to conservative
      therapy, VP or VA shunting. SEARCH METHODS: We searched for eligible studies
      using ALOIS: a comprehensive register of dementia studies, The Cochrane Central
      Register of Controlled Trials (CENTRAL) and several bibliographic databases such
      as MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost)
      and LILACS (BIREME).We also searched the Database of Abstracts of Reviews of
      Effects (DARE) to identify potentially relevant reviews. The search strategy was
      adapted for other databases, using the most appropriate controlled vocabulary for
      each. We did not apply any language or time restrictions. The searches were
      performed in August 2014. SELECTION CRITERIA: We included randomised controlled
      trials (RCTs) of ETV treatment of iNPH. Patients had to have at least two
      symptoms of the Hakim-Adams triad. Exclusion criteria were obstructive causes of
      hydrocephalus, other significant intracranial pathology and other confirmed
      causes of dementia. The eligible comparators were conservative treatment or
      shunting using VP and VA shunts. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened search results, selected eligible studies, assessed risk
      of bias and extracted data. We contacted trial authors for additional data. MAIN
      RESULTS: Only one study met the inclusion criteria: an RCT comparing
      effectiveness of ETV and non-programmable VP shunts in 42 patients with iNPH. The
      study was conducted in Brazil between 2009 and 2012. The overall study risk of
      bias was high. The primary outcome in the study was the proportion of patients
      with improved symptoms one year after surgery, determined as a change of at least
      two points on the Japanese NPH scale. Due to imprecision in the results, it was
      not possible to determine whether there was any difference between groups in the
      proportion of patients who improved 3 or 12 months after surgery (3 months: odds
      ration (OR) 1.12, 95% confidence interval (CI) 0.26 to 4.76, n = 42; 12 months:
      OR 2.5, 95% CI 0.62 to 10.11, n = 38). We were unable to estimate the effect of
      treatment on other efficacy outcomes (cognition, balance, function, gait and
      mobility) because they were inadequately reported. Of the 26 patients in the VP
      shunting group, 5 developed subdural hematoma postoperatively, while there were
      no complications among the 16 patients in the ETV group (OR 0.12, 95% CI 0.01 to
      2.3, n = 42), but the estimate was too imprecise to determine whether this was
      likely to reflect a true difference in complication rates. This was also the case
      for rates of further surgical intervention (OR 1.4, 95% CI 0.31 to 6.24, n = 42).
      There were no deaths during the trial. We judged the quality of evidence for all
      outcomes to be very low because of a high risk of selection, attrition and
      reporting bias and serious imprecision in the results. AUTHORS' CONCLUSIONS: The
      only randomised trial of ETV for iNPH compares it to an intervention which is not
      a standard practice (VP shunting using a non-programmable valve). The evidence
      from this study is inconclusive and of very low quality. Clinicians should be
      aware of the limitations of the evidence. There is a need for more robust
      research on this topic to be able to determine the effectiveness of ETV in
      patients with iNPH.

PMID- 26222252
TI  - Repurposing Clinical Molecule Ebselen to Combat Drug Resistant Pathogens.
AB  - Without a doubt, our current antimicrobials are losing the battle in the fight
      against newly-emerged multidrug-resistant pathogens. There is a pressing, unmet
      need for novel antimicrobials and novel approaches to develop them; however, it
      is becoming increasingly difficult and costly to develop new antimicrobials. One
      strategy to reduce the time and cost associated with antimicrobial innovation is
      drug repurposing, which is to find new applications outside the scope of the
      original medical indication of the drug. Ebselen, an organoselenium clinical
      molecule, possesses potent antimicrobial activity against clinical multidrug
      resistant Gram-positive pathogens, including Staphylococcus, Streptococcus, and
      Enterococcus, but not against Gram-negative pathogens. Moreover, the activity of
      ebselen against Gram-positive pathogens exceeded those activities determined for
      vancomycin and linezolid, drugs of choice for treatment of Enterococcus and
      Staphylococcus infections. The minimum inhibitory concentrations of ebselen at
      which 90% of clinical isolates of Enterococcus and Staphylococcus were inhibited
      (MIC90) were found to be 0.5 and 0.25 mg/L, respectively. Ebselen showed
      significant clearance of intracellular methicillin-resistant S. aureus (MRSA) in
      comparison to vancomycin and linezolid. We demonstrated that ebselen inhibits the
      bacterial translation process without affecting mitochondrial biogenesis.
      Additionally, ebselen was found to exhibit excellent activity in vivo in a
      Caenorhabditis elegans MRSA-infected whole animal model. Finally, ebselen showed
      synergistic activities with conventional antimicrobials against MRSA. Taken
      together, our results demonstrate that ebselen, with its potent antimicrobial
      activity and safety profiles, can be potentially used to treat multidrug
      resistant Gram-positive bacterial infections alone or in combination with other
      antibiotics and should be further clinically evaluated. 

PMID- 26222253
TI  - Non-Hematopoietic and Hematopoietic SIRPalpha Signaling Differently Regulates
      Murine B Cell Maturation in Bone Marrow and Spleen.
AB  - B lymphocyte development occurs in the bone marrow, while final differentiation
      and maturation can occur in both the bone marrow and the spleen. Here we provide
      evidence that signal regulatory protein alpha (SIRPalpha), an Ig-superfamily ITIM
      receptor expressed by myeloid but not by lymphoid cells, is involved in
      regulating B cell maturation. Lack of SIRPalpha signaling in adult SIRPalpha
      mutant mice resulted in a reduced maturation of B cells in the bone marrow,
      evident by reduced numbers of semi-mature IgD+IgMhi follicular type-II (F-II) and
      mature IgD+IgMlo follicular type-I (F-I) B cells, as well as reduced blood B cell
      numbers. In addition, lack of SIRPalpha signaling also impaired follicular B cell
      maturation in the spleen. Maturing BM or splenic B cells of SIRPalpha-mutant mice
      were found to express higher levels of the pro-apoptotic protein BIM and
      apoptosis was increased among these B cells. Bone marrow reconstitution
      experiments revealed that the B cell maturation defect in bone marrow and blood
      was due to lack of SIRPalpha signaling in non-hematopoietic cells, while
      hematopoietic SIRPalpha signaling was important for follicular B cell maturation
      in the spleen. Adding on to our previous findings of a stromal cell defect in
      SIRPalpha-mutant mice was the finding that gene expression of receptor activator
      of nuclear factor-KB ligand (RANKL) was significantly lower in cultured bone
      marrow stromal cells of SIRPalpha mutant mice. These data suggest a novel and
      opposite contribution of SIRPalpha signaling within non-hematopoietic and
      hematopoietic cells, respectively, to maintain B cell maturation and to prevent
      apoptosis in the bone marrow and spleen of adult mice. 

PMID- 26222254
TI  - Efficient Expression of Igf-1 from Lentiviral Vectors Protects In Vitro but Does
      Not Mediate Behavioral Recovery of a Parkinsonian Lesion in Rats.
AB  - Gene therapy approaches delivering neurotrophic factors have offered promising
      results in both preclinical and clinical trials of Parkinson's disease (PD).
      However, failure of glial cell line-derived neurotrophic factor in phase 2
      clinical trials has sparked a search for other trophic factors that may retain
      efficacy in the clinic. Direct protein injections of one such factor, insulin
      like growth factor (IGF)-1, in a rodent model of PD has demonstrated impressive
      protection of dopaminergic neurons against 6-hydroxydopamine (6-OHDA) toxicity.
      However, protein infusion is associated with surgical risks, pump failure, and
      significant costs. We therefore used lentiviral vectors to deliver Igf-1, with a
      particular focus on the novel integration-deficient lentiviral vectors (IDLVs). A
      neuron-specific promoter, from the human synapsin 1 gene, excellent for gene
      expression from IDLVs, was additionally used to enhance Igf-1 expression. An
      investigation of neurotrophic effects on primary rat neuronal cultures
      demonstrated that neurons transduced with IDLV-Igf-1 vectors had complete
      protection on withdrawal of exogenous trophic support. Striatal transduction of
      such vectors into 6-OHDA-lesioned rats, however, provided neither protection of
      dopaminergic substantia nigra neurons nor improvement of animal behavior. 

PMID- 26222255
TI  - Non-target stimuli in the visual field influence movement preparation in upper
      limb reaching.
AB  - The present work provides an empirical test of the Dynamic Field Theory of
      visuospatial cognition. The Dynamic Field Theory is a bi-stable neural network
      model applied to explain how visual information is integrated during the
      preparation of reaching responses (Erlhagen and Schoner). The dynamic field
      theory posits that motor cortices develop peaks of activation for each possible
      target in the visual field. Targets that are close in space produce neural peaks
      with overlapping distributions, whereas targets that are far apart produce
      distinct peaks with non-overlapping distributions. As such, the Dynamic Field
      Theory predicts reaction times to potential targets that are close in space will
      be faster than those to targets that are far apart. The present work examined how
      proximal and distal distractors impact reaction time in an upper-limb reaching
      task. The results demonstrated that distal distractors result in prolonged
      reaction times compared to proximal distractors. We suggest that reaction time
      represents the time required to inhibit neural activity representing the location
      of the distractor. Thus, prolonged reaction times observed for distal distractors
      reflect the temporal demands associated with the competition of two non
      overlapping distributions of activity in the brain. These findings support the
      tenets of the Dynamic Field Theory and demonstrate that non-target stimuli in the
      visual field can influence movement preparation. 

PMID- 26222256
TI  - Contribution of maternal oxygenic state to the effects of chronic postnatal
      hypoxia on mouse body and brain development.
AB  - 1-2% of live births are to very low birth weight, premature infants that often
      show a developmental trajectory plagued with neurological sequelae including
      ventriculomegaly and significant decreases in cortical volume. We are able to
      recapitulate these sequelae using a mouse model of hypoxia where early postnatal
      pups are exposed to chronic hypoxia for one week. However, because the timing of
      hypoxic exposure occurs so early in development, dams and pups are housed
      together in the hypoxic chamber, and therefore, dams are also subjected to the
      same hypoxic conditions as the pups. To understand the relative contribution of
      hypoxia directly on the pups as opposed to the indirect contribution mediated by
      the effects of hypoxia and potential alterations in the dam's care of the pups,
      we examined whether reducing the dams exposure to hypoxia may significantly
      increase pup outcomes on measures that we have found consistently changed
      immediately following chronic hypoxia exposure. To achieve this, we rotated dams
      between normoxic and hypoxic conditions, leaving the litters untouched in their
      respective conditions and compared gross anatomical measures of normoxic and
      hypoxic pups with non-rotating or rotating mothers. As we expected, hypoxic
      rearing decreased pup body weight, brain weight and cortical volume. Reducing the
      dam's exposure to hypoxic conditions actually amplified the effects of hypoxia on
      body weight, such that hypoxic pups with rotating mothers showed significantly
      less growth. Interestingly, rotation of hypoxic mothers did not have the same
      deleterious effect on brain weight, suggesting the presence of compensatory
      mechanisms conserving brain weight and development even under extremely low body
      weight conditions. The factors that potentially contribute to these compensatory
      changes remain to be determined, however, nutrition, pup feeding/metabolism, or
      changes in maternal care are important candidates, acting either together or
      independently to change pup body and brain development. 

PMID- 26222257
TI  - Pleiotrophin modulates morphine withdrawal but has no effects on morphine
      conditioned place preference.
AB  - Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction
      and neurodegenerative disorders. Morphine administration induces an increase in
      the expression of PTN and Midkine (MK), the only other member of this family of
      cytokines, in brain areas related with the addictive effects of drug of abuse,
      like the Ventral Tegmental Area or the hippocampus. In spite of previous studies
      showing that PTN modulates amphetamine and ethanol rewarding effects, and that
      PTN is involved in morphine-induced analgesia, it was still unknown if the
      rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to
      study the role of PTN in the reward and physical dependence induced by morphine.
      We used the Conditioned Place Preference (CPP) paradigm in PTN genetically
      deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of
      morphine in absence of endogenous PTN. Second, to study if PTN may be involved in
      morphine physical dependence, naloxone-precipitated withdrawal syndrome was
      induced in PTN-/- and WT morphine dependent mice. Although the increase in the
      time spent in the morphine-paired compartment after conditioning tended to be
      more pronounced in PTN-/- mice, statistical significance was not achieved. The
      data suggest that PTN does not exert an important role in morphine reward.
      However, our results clearly indicate that PTN-/- mice develop a more severe
      withdrawal syndrome than WT mice, characterized as a significant increase in the
      time standing and in the total incidences of forepaw licking, forepaw tremors,
      wet dog shake and writhing. The data presented here suggest that PTN is a novel
      genetic factor that plays a role in morphine withdrawal syndrome. 

PMID- 26222258
TI  - How does the ketogenic diet induce anti-seizure effects?
AB  - The high-fat ketogenic diet (KD) is a remarkably effective treatment for
      medically intractable epilepsy and has been part of the clinical armamentarium
      for nearly a century. However, the mechanisms underlying the KD's actions have
      remained elusive. Over the past decade, there has been phenomenal international
      growth of clinical centers offering metabolism-based therapies for epilepsy, and
      rapidly expanding research into the cellular and biochemical effects induced by
      the KD. At present, there are many hypotheses regarding KD action, and while each
      is uniquely compelling, it is becoming more apparent that the KD likely works
      through multiple mechanisms that target fundamental biochemical pathways linked
      to cellular substrates (e.g., ion channels) and mediators responsible for
      neuronal hyperexcitability. This is not altogether surprising given the
      complexity of the epileptic brain, and the many different pathophysiologic
      mechanisms that underlie seizure genesis and epileptogenicity. The scientific
      literature involving the KD strongly supports the notion that epilepsy may indeed
      in part represent a "metabolic disease", and that this concept could serve as a
      novel framework for the development of more effective anti-seizure drugs.

PMID- 26222259
TI  - Manipulating neuronal activity in the mouse brain with ultrasound: A comparison
      with optogenetic activation of the cerebral cortex.
AB  - Low-intensity focused ultrasound induces neuronal activation via mechanisms that
      remain to be elucidated. We recorded local field potential fluctuations in the
      motor cortex in response to ultrasound stimulation of the somatosensory barrel
      cortex, comparing them to those recorded in response to optogenetic stimulation
      of interneurons and pyramidal neurons of the somatosensory cortex in the same
      animals. Comparison of the waveform produced by ultrasound stimulation to those
      produced by optogenetic stimulation revealed similarities between ultrasound
      induced responses and optogenetically-induced responses to pyramidal cell
      stimulation, but not interneuron stimulation, which may indicate that ultrasound
      stimulation is mediated by excitation of cerebral cortical pyramidal neurons.
      Comparison of post mortem evoked responses to responses in living tissue
      confirmed the necessity for excitable tissue in the evoked response.
      Collectively, these experiments demonstrate an excitation-dependent response to
      low-frequency transdural ultrasound stimulation of cerebral cortical neuronal
      activity. 

PMID- 26222260
TI  - Overexpression of DJ-1 protects against C2-ceramide-induced neuronal death
      through activation of the PI3K/AKT pathway and inhibition of autophagy.
AB  - Parkinson's disease (PD) is the second most frequent neurodegenerative disorder.
      It is characterized by selective degeneration of dopaminergic neurons in the
      substantia nigra pars compacta (SNpc). Early-onset familial forms of PD are
      associated with mutations in several genes, including parkin, pink1 and dj-1. DJ
      1 encodes a protein whose neuroprotective function has not been completely
      clarified yet. We aim to understand the neuroprotective mechanisms of DJ-1, in
      particular, DJ-1's involvement in the regulation of the PI3K/PTEN/AKT/mTOR
      pathway and neuronal autophagy in a neurotoxic context induced by C2-ceramide, by
      using CAD cells, a murine cathecolaminergic cell line. We demonstrated that C2
      ceramide induces CAD cell death associated with decreased phosphorylation of PTEN
      at Ser380, AKT at Ser473, and mTOR at Ser2448; and increased of autophagic flux
      (increased LC3-II and autophagosome formation). Additionally, we showed that
      overexpression of DJ-1 protects against C2-ceramide-induced neuronal death and it
      is not associated with change in the phosphorylation of mTOR at Ser2448. In
      conclusion, these data suggest that DJ-1 reinforces the PI3K/AKT survival pathway
      and inhibits autophagy, probably by a mechanism independent from mTOR. 

PMID- 26222261
TI  - Can Unmanned Aerial Systems (Drones) Be Used for the Routine Transport of
      Chemistry, Hematology, and Coagulation Laboratory Specimens?
AB  - BACKGROUND: Unmanned Aerial Systems (UAS or drones) could potentially be used for
      the routine transport of small goods such as diagnostic clinical laboratory
      specimens. To the best of our knowledge, there is no published study of the
      impact of UAS transportation on laboratory tests. METHODS: Three paired samples
      were obtained from each one of 56 adult volunteers in a single phlebotomy event
      (336 samples total): two tubes each for chemistry, hematology, and coagulation
      testing respectively. 168 samples were driven to the flight field and held
      stationary. The other 168 samples were flown in the UAS for a range of times,
      from 6 to 38 minutes. After the flight, 33 of the most common chemistry,
      hematology, and coagulation tests were performed. Statistical methods as well as
      performance criteria from four distinct clinical, academic, and regulatory bodies
      were used to evaluate the results. RESULTS: Results from flown and stationary
      sample pairs were similar for all 33 analytes. Bias and intercepts were <10% and
      <13% respectively for all analytes. Bland-Altman comparisons showed a mean
      difference of 3.2% for Glucose and <1% for other analytes. Only bicarbonate did
      not meet the strictest (Royal College of Pathologists of Australasia Quality
      Assurance Program) performance criteria. This was due to poor precision rather
      than bias. There were no systematic differences between laboratory-derived
      (analytic) CV's and the CV's of our flown versus terrestrial sample pairs however
      CV's from the sample pairs tended to be slightly higher than analytic CV's. The
      overall concordance, based on clinical stratification (normal versus abnormal),
      was 97%. Length of flight had no impact on the results. CONCLUSIONS:
      Transportation of laboratory specimens via small UASs does not affect the
      accuracy of routine chemistry, hematology, and coagulation tests results from
      selfsame samples. However it results in slightly poorer precision for some
      analytes.

PMID- 26222263
TI  - The low photo-inactivation rate of bacteria in human plasma II. Inhibition of
      methylene blue bleaching in plasma and effective bacterial destruction by the
      addition of dilute acetic acid to human plasma.
AB  - Methylene blue (MB) and other photo-sensitizer molecules have been recognized as
      effective means for the inactivation of bacteria and other pathogens owing to
      their ability to photo-generate reactive oxygen species (ROS) including singlet
      oxygen. These reactive species react with the membrane of the bacteria causing
      their destruction. However, the efficiency of MB to destroy bacteria in plasma is
      very low because the MB 660 nm absorption band, that is responsible for the ROS
      generation, is bleached. The bleaching of MB, in plasma, is caused by the
      attachment of a hydrogen atom to the central ring nitrogen of MB, which destroys
      the ring conjugation and forms Leuco-MB which does not absorb in the 600 nm
      region. In this paper we show that addition of dilute acetic acid, ~10(-4) M, to
      human plasma, prevents H-atom attachment to MB, allowing MB to absorb at 660 nm,
      generates singlet oxygen and thus inactivates bacteria. The mechanism proposed,
      for preventing MB bleaching in plasma, is based on the oxidation of cysteine to
      cystine, by reaction with added dilute acetic acid, thus eliminating the
      availability of the thiol hydrogen atom which attaches to the MB nitrogen. It is
      expected that the addition of acetic acid to plasma will be effective in the
      sterilization of plasma and killing of bacteria in wounds and burns. 

PMID- 26222262
TI  - Rapid and MR-Independent IK1 Activation by Aldosterone during Ischemia
      Reperfusion.
AB  - In ST elevation myocardial infarction (STEMI) context, clinical studies have
      shown the deleterious effect of high aldosterone levels on ventricular arrhythmia
      occurrence and cardiac mortality. Previous in vitro reports showed that during
      ischemia-reperfusion, aldosterone modulates K+ currents involved in the holding
      of the resting membrane potential (RMP). The aim of this study was to assess the
      electrophysiological impact of aldosterone on IK1 current during myocardial
      ischemia-reperfusion. We used an in vitro model of "border zone" using right
      rabbit ventricle and standard microelectrode technique followed by cell-attached
      recordings from freshly isolated rabbit ventricular cardiomyocytes. In
      microelectrode experiments, aldosterone (10 and 100 nmol/L, n=7 respectively)
      increased the action potential duration (APD) dispersion at 90% between ischemic
      and normoxic zones (from 95+/-4 ms to 116+/-6 ms and 127+/-5 ms respectively,
      P<0.05) and reperfusion-induced sustained premature ventricular contractions
      occurrence (from 2/12 to 5/7 preparations, P<0.05). Conversely, potassium
      canrenoate 100 nmol/L and RU 28318 1 MUmol/l alone did not affect AP parameters
      and premature ventricular contractions occurrence (except Vmax which was
      decreased by potassium canrenoate during simulated-ischemia). Furthermore,
      aldosterone induced a RMP hyperpolarization, evoking an implication of a K+
      current involved in the holding of the RMP. Cell-attached recordings showed that
      aldosterone 10 nmol/L quickly activated (within 6.2+/-0.4 min) a 30 pS K+
      selective current, inward rectifier, with pharmacological and biophysical
      properties consistent with the IK1 current (NPo =1.9+/-0.4 in control vs
      NPo=3.0+/-0.4, n=10, P<0.05). These deleterious effects persisted in presence of
      RU 28318, a specific MR antagonist, and were successfully prevented by potassium
      canrenoate, a non specific MR antagonist, in both microelectrode and patch-clamp
      recordings, thus indicating a MR-independent IK1 activation. In this ischemia
      reperfusion context, aldosterone induced rapid and MR-independent deleterious
      effects including an arrhythmia substrate (increased APD90 dispersion) and
      triggered activities (increased premature ventricular contractions occurrence on
      reperfusion) possibly related to direct IK1 activation. 

PMID- 26222264
TI  - Negative Effect of Proton-pump Inhibitors (PPIs) on Helicobacter pylori Growth,
      Morphology, and Urease Test and Recovery after PPI Removal--An In vitro Study.
AB  - BACKGROUND: Proton-pump inhibitor (PPI) consumption does lead to false-negative
      results of Helicobacter pylori diagnostic tests such as biopsy culture and rapid
      urease test (RUT). MATERIALS AND METHODS: Helicobacter pylori isolates from 112
      dyspeptic patients with (56.5%) or without (43.5%) PPI consumption were recruited
      for examining the negative effects of omeprazole (OMP), lansoprazole (LPZ), and
      pantoprazole (PAN) on H. pylori viability, morphology, and urease, in vitro. The
      effect of a sublethal concentration of OMP on bacterial features and their
      recovery after removal of OMP was also assessed. RESULTS: Of 112 culture-positive
      gastric biopsies, 87.5% were RUT positive and 12.5% RUT negative. There was a
      significant correlation between negative RUT results and PPI consumption (p <
      .05). OMP (minimum inhibitory concentration, MIC 32 MUg/mL) and LPZ (MIC 8
      MUg/mL) inhibited the growth of 78.6% of H. pylori isolates. OMP and LPZ
      inhibited urease of 90.3% of isolates between 0 and 40 minutes and 54.4% between
      20 and 40 minutes, respectively. PAN did not inhibit H. pylori growth and urease.
      Three 3-day (9 days) consecutive subcultures of H. pylori on brucella blood agar
      (BBA) supplemented with OMP resulted in reduced bacterial viability (1+),
      compared with control (4+), change of spiral morphology to coccoid, and reduction
      in pink color intensity in urea agar. Bacterial growth (1+), morphology, and
      urease test did not improve after the first 3-day and second 3-day (6 days)
      subcultures on BBA. However, relative recovery occurred after the third 3-day (9
      days) subculture and complete recovery was observed after the fourth 3-day (12
      days) subculture, as confluent growth (4+), 100% spiral cells, and strong urease
      test. CONCLUSION: Proton-pump Inhibitors exert transient negative effects on H.
      pylori viability, morphology, and urease test. Accordingly, cessation of PPI
      consumption at least 12 days before endoscopy could help avoiding false-negative
      results of H. pylori diagnostic tests.

PMID- 26222265
TI  - Allele-Selective Inhibition of Mutant Huntingtin with 2-Thio- and C5-
      Triazolylphenyl-Deoxythymidine-Modified Antisense Oligonucleotides.
AB  - We report the effect of introducing a single incorporation of 2-thio
      deoxythymidine (2S-dT) or C5-Triazolylphenyl-deoxythymidine (5-TrPh-dT) at four
      positions within the gap region of RNase H gapmer antisense oligonucleotides
      (ASOs) for reducing wild-type and mutant huntingtin mRNA in human patient
      fibroblasts. We show that these modifications can modulate processing of the
      ASO/RNA heteroduplexes by recombinant human RNase H1 in a position-dependent
      manner. We also created a structural model of the catalytic domain of human RNase
      H bound to ASO/RNA heteroduplexes to rationalize the activity and selectivity
      observations in cells and in the biochemical assays. Our results highlight the
      ability of chemical modifications in the gap region to produce profound changes
      in ASO behavior. 

PMID- 26222266
TI  - Late presentation to HIV testing is overestimated when based on the consensus
      definition.
AB  - OBJECTIVES: In 2011, a consensus was reached defining "late presenters" (LPs) as
      individuals presenting for care with a CD4 count < 350 cells/MUL or with an AIDS
      defining event, regardless of CD4 count. However, a transient low CD4 count is
      not uncommon in recent infections. The objective of this study was to investigate
      how measurements of late presentation change if the clinical stage at the time of
      diagnosis is taken into account. METHODS: Case surveillance data for newly
      diagnosed patients in Belgium in 1998-2012 were analysed, including CD4 count at
      diagnosis, the presence of AIDS-defining events, and recent infections (< 6
      months) as reported by clinicians in the case of acute illness or a recent
      negative test. First, proportions of LPs were calculated according to the
      consensus definition. Secondly, LPs were reclassified as "nonlate" if infections
      were reported as recent. RESULTS: A total of 7949 HIV diagnoses were included in
      the study. Recent infections were increasingly reported over time, accounting for
      8.2% of new infections in 1998 and 37.5% in 2012. The consideration of clinical
      stage significantly modified the proportion of LPs: 18.2% of men who have sex
      with men (MSM) diagnosed in 2012 would be classified as LPs instead of 30.9%
      using the consensus definition (P < 0.001). The proportion of patients
      misclassified as LPs increased significantly over time: 5% in MSM in 1998 vs. 41%
      in 2012. CONCLUSIONS: This study suggests that low CD4 counts in recent
      infections may lead to overestimation of late presentation when applying the
      consensus definition. The impact of transient CD4 count on late presentation
      estimates should be assessed and, if relevant, the introduction of clinical stage
      in the definition of late presentation should be considered.

PMID- 26222267
TI  - Adhesion and Atomic Structures of Gold on Ceria Nanostructures: The Role of
      Surface Structure and Oxidation State of Ceria Supports.
AB  - We report an aberration-corrected electron microscopy analysis of the adhesion
      and atomic structures of gold nanoparticle catalysts supported on ceria nanocubes
      and nanorods. Under oxidative conditions, the as-prepared gold nanoparticles on
      the ceria nanocubes have extended atom layers at the metal-support interface. In
      contrast, regular gold nanoparticles and rafts are present on the ceria nanorod
      supports. Under the reducing conditions of water-gas shift reaction, the extended
      gold atom layers and rafts vanish. In addition, the gold particles on the
      nanocubes change in morphology and increase in size while those on the nanorods
      are almost unchanged. The size, morphology, and atomic interface structures of
      gold strongly depend on the surface structures of ceria supports ((100) surface
      versus (111) surface) and the reaction environment (reductive versus oxidative).
      These findings provide insights into the deactivation mechanisms and the shape
      dependent catalysis of oxide supported metal catalysts. 

PMID- 26222268
TI  - Shared and nonshared genomic divergence in parallel ecotypes of Littorina
      saxatilis at a local scale.
AB  - Parallel speciation occurs when selection drives repeated, independent adaptive
      divergence that reduces gene flow between ecotypes. Classical examples show
      parallel speciation originating from shared genomic variation, but this does not
      seem to be the case in the rough periwinkle (Littorina saxatilis) that has
      evolved considerable phenotypic diversity across Europe, including several
      distinct ecotypes. Small 'wave' ecotype snails inhabit exposed rocks and
      experience strong wave action, while thick-shelled, 'crab' ecotype snails are
      larger and experience crab predation on less exposed shores. Crab and wave
      ecotypes appear to have arisen in parallel, and recent evidence suggests only
      marginal sharing of molecular variation linked to evolution of similar ecotypes
      in different parts of Europe. However, the extent of genomic sharing is expected
      to increase with gene flow and more recent common ancestry. To test this, we used
      de novo RAD-sequencing to quantify the extent of shared genomic divergence
      associated with phenotypic similarities amongst ecotype pairs on three close
      islands (<10 km distance) connected by weak gene flow (Nm ~ 0.03) and with recent
      common ancestry (<10 000 years). After accounting for technical issues, including
      a large proportion of null alleles due to a large effective population size, we
      found ~8-28% of positive outliers were shared between two islands and ~2-9% were
      shared amongst all three islands. This low level of sharing suggests that
      parallel phenotypic divergence in this system is not matched by shared genomic
      divergence despite a high probability of gene flow and standing genetic
      variation.

PMID- 26222269
TI  - Isolation and identification of polyphenols from Marsilea quadrifolia with
      antioxidant properties in vitro and in vivo.
AB  - Marsilea quadrifolia is an edible aquatic medicinal plant used as a traditional
      health food in Asia. Four new polyphenols including kaempferol 3-O-(2"-O-E
      caffeoyl)-beta-d-glucopyranoside (1), kaempferol 3-O-(3"-O-E-caffeoyl)-alpha-l
      arabinopyranoside (3), 4-methy-3'-hydroxypsilotinin (4) and (+/-)-(E)-4b-methoxy
      3b,5b-dihydroxyscirpusin A (18) together with 14 known ones (2, 5-17) were
      isolated from the ethanol extract of M. quadrifolia. Structures of the new
      compounds were elucidated by extensive spectroscopic analyses. In DPPH and oxygen
      radical absorbance capacity antioxidant assays, some compounds showed stronger
      antioxidant activities and quercetin (9) was the most potent antioxidant in both
      assays. In a restraint-induced oxidative stress model in mice, quercetin
      significantly attenuated the increase in plasma ALT and AST levels as well as
      liver MDA content of restrained mice. Liver SOD activity was also significantly
      increased by quercetin, indicating a significant in vivo antioxidant activity. As
      a rich source of polyphenols with strong antioxidant activities, M. quadrifolia
      may be developed to a product for relieving oxidative stress. 

PMID- 26222271
TI  - Spin Transition and Structural Transformation in a Mononuclear Cobalt(II)
      Complex.
AB  - A mononuclear compound, [Co(II)(pyterpy)2](PF6)2.2CH3OH [2; pyterpy = 4'-(4'''
      pyridyl)-2,2':6',2"-terpyridine], shows a phase-transition-coupled, abrupt spin
      transition with a 9 K wide hysteresis that can transform to a spin-crossover
      compound, [Co(II)(pyterpy)2](PF6)2.2CH2Cl2.CH3OH (3). 

PMID- 26222270
TI  - Randomized controlled study in pregnancy on treatment of marked hyperglycemia
      that is short of overt diabetes.
AB  - INTRODUCTION: A randomized multicenter study was conducted in the Stockholm
      Orebro areas in Sweden to evaluate how treatment aiming at normoglycemia affects
      fetal growth, pregnancy and neonatal outcome in pregnant women with severe
      hyperglycemia. MATERIAL AND METHODS: Pregnant women with hyperglycemia defined as
      fasting capillary plasma glucose <7.0 mmol/L and a two-hour plasma glucose value
      >=10.0 and <12.2 mmol/L following a 75-g oral glucose tolerance test (OGTT)
      diagnosed before 34 weeks of gestation were randomized to treatment (n = 33) or
      controls (n = 36). Women assigned to the control group were blinded for the OGTT
      results and received routine care. The therapeutic goal was fasting plasma
      glucose 4-5 mmol/L, and <6.5 mmol/L after a meal. Primary outcomes were size at
      birth and number of large-for-gestational age (>90th percentile) neonates.
      Secondary outcomes were pregnancy complications, neonatal morbidity and glycemic
      control. RESULTS: The planned number of participating women was not reached.
      There was a significantly reduced rate of large-for-gestational age neonates, 21
      vs. 47%, P < 0.05. Group differences in pregnancy complications and neonatal
      morbidity were not detected because of limited statistical power. In total, 66.7%
      of the women in the intervention group received insulin. Of all measured plasma
      glucose values, 64.1% were in the target range, 7.2% in the hypoglycemic range
      and 28.7% above target values. There were no cases of severe hypoglycemia.
      CONCLUSIONS: Aiming for normalized glycemia in a pregnancy complicated by severe
      hyperglycemia reduces fetal growth but is associated with an increased rate of
      mild hypoglycemia.

PMID- 26222272
TI  - BF3.OEt2-Promoted Synthesis of 2,3-Metallocenocyclohexanones: A 1,2-Hydride Shift
      and Cationic Cyclization Strategy.
AB  - A BF3.OEt2-promoted cyclization of metallocenyl enones to form cyclohexanone
      fused metallocenes is reported. 2,3-Metallocenocyclohexanones were formed
      exclusively, and no normal Nazarov-type cyclopentanone analogues were detected.
      The reaction possibly proceeded via an unusual cationic 1,2-hydride shift
      followed by Friedel-Crafts alkylative cyclization process. During the studies of
      the alkylation reaction of these keto esters, an unusual and rare facial
      selectivity was observed. The electrophiles would be attacked from the same face
      as the second Cp ring. 

PMID- 26222273
TI  - Role of Cobalt Content in Improving the Low-Temperature Performance of Layered
      Lithium-Rich Cathode Materials for Lithium-Ion Batteries.
AB  - Layered lithium-rich cathode material, Li1.2Ni0.2-xCo2xMn0.6-xO2 (x = 0-0.05) was
      successfully synthesized using a sol-gel method, followed by heat treatment. The
      effects of trace amount of cobalt doping on the structure, morphology, and low
      temperature (-20  degrees C) electrochemical properties of these materials are
      investigated systematically. X-ray diffraction (XRD) results confirm that the Co
      has been doped into the Ni/Mn sites in the transition-metal layers without
      destroying the pristine layered structure. The morphological observations reveal
      that there are no changes of morphology or particle size after Co doping. The
      electrochemical performance results indicate that the discharge capacities and
      operation voltages are drastically lowered along with the decreasing temperature,
      but their fading rate becomes slower when increasing the Co contents. At -20 
      degrees C, the initial discharge capacity of sample with x = 0 could retain only
      22.1% (57.3/259.2 mAh g(-1)) of that at 30  degrees C, while sample with x = 0.05
      could maintain 39.4% (111.3/282.2 mAh g(-1)). Activation energy analysis and
      electrochemical impedance spectroscopy (EIS) results reveal that such an
      enhancement of low-temperature discharge capacity is originated from the easier
      interface reduction reaction of Ni(4+) or Co(4+) after doping trace amounts of
      Co, which decreases the activation energy of the charge transfer process above
      3.5 V during discharging. 

PMID- 26222274
TI  - New radiopharmaceutical agents for the treatment of castration-resistant prostate
      cancer.
AB  - Prostate cancer (PCa) is the fourth most common cancer worldwide in terms of
      incidence and third among male, but is becoming the most common cancer in
      developed countries. In many patients the disease will progress despite of
      castration levels of testosterone, to become castration-resistant PCa (CRPC).
      Nearly all patients with CRPC show bone metastases. The treatment of patients
      with bony metastases has dramatically changed during the past three years because
      of new therapeutic approaches addressed to obtain pain control, reduced skeletal
      morbidity, and most importantly, increased survival rate. A possible therapy can
      be based also on the use of radiopharmaceuticals systemically administered to
      slow or reverse the bone metastatic progression. In facts bone-homing
      radiopharmaceuticals are taken up in areas of high bone turnover, including areas
      with high osteoblastic activity. Recently, a bone targeting radiopharmaceutical,
      Radium-223 dichloride was added to this group of drugs clearly representing a new
      generation of radiopharmaceutical in bone therapy. Clinical trials had shown that
      the treatment with Ra-223 allowed the reduction of the risk of death respect to
      placebo. No other radiometabolic treatment achieved such result, evidentiating
      the disease-modifying properties of this bone-homing radiopharmaceutical. In an
      effort to treat patients with disseminated PCa, who became resistant to hormonal
      therapy, molecular targets have been recently identified. Prostate specific
      membrane antigen (PSMA) is one attractive target for diagnosis and therapy of
      metastasized PCa since its expression levels are directly correlated to androgen
      independence, metastasis, and progression. Gastrin-releasing peptide receptors
      (GRPr) are also highly overexpressed in PCa. Numerous studies suggest the
      possibility of a high PCa-specific signal with radiolabeled bombesin analogs
      targeting GRPr. Low molecular weight peptides directed against these molecular
      targets have been radiolabeled with positron emitting radionuclides such as 68Ga
      in order to improve sensitivity and specificity for detecting primary,
      metastatic, and recurrent PCa by PET/CT over conventional imaging techniques.
      Although peptide radionuclide ligand therapy studies have just initiated, the
      diagnostic relevance of 68Ga labeled specific tracers has already been
      established its clinical utility and represents a valid tool against this common
      and deadly cancer. 

PMID- 26222275
TI  - Role of chemotherapy in combination with hormonal therapy in first-line treatment
      of metastatic hormone-sensitive prostate cancer.
AB  - Prostate cancer (PC) is a heterogeneous disease, whose growth is driven by
      androgens and androgen receptors. Androgen deprivation therapy (ADT) is the
      standard treatment of hormone-naive metastatic disease. The majority of patients
      are treated with medical castration with GnRH agonists or antagonists, which
      usually determines a profound PSA decline and a radiological and clinical
      benefit. However, essentially all patients experience progression to castration
      resistant prostate cancer (CRPC), and overall prognosis remains disappointing.
      Early targeting of cells that survive hormonal therapy may potentially prevent
      the development of CRPC. Several trials have explored the use of combination
      therapy with ADT and chemotherapy, targeting both the androgen dependent and
      independent cells simultaneously. Docetaxel was administered in combination with
      ADT to men with hormone-naive metastatic prostate cancer, in the attempt to
      improve the duration and quality of patient survival. Three large randomized
      trials (the GETUG-15, CHAARTED and more recently the STAMPEDE study) have
      assessed these endpoints, with partially conflicting results. Overall, the
      results from these trials seem to support the use of early docetaxel combined
      with ADT in selected hormone-naive metastatic PC patients. Full publication of
      the results of all studies, with longer follow-up, and the results of other
      ongoing trials in this setting will hopefully further define the role and the
      indications of this therapeutic strategy. 

PMID- 26222276
TI  - Direct tandem mass spectrometric analysis of amino acids in plasma using fluorous
      derivatization and monolithic solid-phase purification.
AB  - In this study, we developed a novel direct tandem mass spectrometric method for
      rapid and accurate analysis of amino acids utilizing a fluorous derivatization
      and purification technique. Amino acids were perfluoroalkylated with 2H,2H,3H,3H
      perfluoroundecan-1-al in the presence of 2-picoline borane via reductive
      amination. The derivatives were purified by perfluoroalkyl-modified silica-based
      monolithic solid-phase extraction (monolithic F-SPE), and directly analyzed by
      tandem mass spectrometry using electrospray ionization without liquid
      chromatographic separation. The perfluoroalkyl derivatives could be sufficiently
      distinguished from non-fluorous compounds, i.e. the biological matrix, due to
      their fluorous interaction. Thus, rapid and accurate determination of amino acids
      was accomplished. The method was validated with human plasma samples and applied
      to the analysis of amino acids in the plasma of mice with maple syrup urine
      disease or phenylketonuria.

PMID- 26222277
TI  - Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and
      Acute Lung Injury.
AB  - The cation channel transient receptor potential vanilloid (TRPV) 4 is expressed
      in endothelial and immune cells; however, its role in acute lung injury (ALI) is
      unclear. The functional relevance of TRPV4 was assessed in vivo, in isolated
      murine lungs, and in isolated neutrophils. Genetic deficiency of TRPV4 attenuated
      the functional, histological, and inflammatory hallmarks of acid-induced ALI.
      Similar protection was obtained with prophylactic administration of the TRPV4
      inhibitor, GSK2193874; however, therapeutic administration of the TRPV4
      inhibitor, HC-067047, after ALI induction had no beneficial effect. In isolated
      lungs, platelet-activating factor (PAF) increased vascular permeability in lungs
      perfused with trpv4(+/+) more than with trpv4(-/-) blood, independent of lung
      genotype, suggesting a contribution of TRPV4 on blood cells to lung vascular
      barrier failure. In neutrophils, TRPV4 inhibition or deficiency attenuated the
      PAF-induced increase in intracellular calcium. PAF induced formation of
      epoxyeicosatrienoic acids by neutrophils, which, in turn, stimulated TRPV4
      dependent Ca(2+) signaling, whereas inhibition of epoxyeicosatrienoic acid
      formation inhibited the Ca(2+) response to PAF. TRPV4 deficiency prevented
      neutrophil responses to proinflammatory stimuli, including the formation of
      reactive oxygen species, neutrophil adhesion, and chemotaxis, putatively due to
      reduced activation of Rac. In chimeric mice, however, the majority of protective
      effects in acid-induced ALI were attributable to genetic deficiency of TRPV4 in
      parenchymal tissue, whereas TRPV4 deficiency in circulating blood cells primarily
      reduced lung myeloperoxidase activity. Our findings identify TRPV4 as novel
      regulator of neutrophil activation and suggest contributions of both parenchymal
      and neutrophilic TRPV4 in the pathophysiology of ALI. 

PMID- 26222278
TI  - Activation of the phosphatidylinositol 3-kinase pathway plays important roles in
      reduction of cerebral infarction by cilnidipine.
AB  - Cerebral infarction causes permanent neuronal loss inducing severe morbidity and
      mortality. Because hypertension is the main risk factor for cerebral infarction
      and most patients with hypertension take antihypertensive drugs daily, the
      neuroprotective effects and mechanisms of anti-hypertensive drugs need to be
      investigated. Cilnidipine, a long-acting, new generation 1,4-dihydropyridine
      inhibitor of both L- and N-type calcium channels, was reported to reduce
      oxidative stress. In this study, we investigated whether cilnidipine has
      therapeutic effects in an animal model of cerebral infarction. After
      determination of the most effective dose of cilnidipine, a total of 128 rats were
      subjected to middle cerebral artery occlusion. Neurobehavioral function test and
      brain MRI were performed, and rats with similar sized infarcts were randomized to
      either the cilnidipine group or the control group. Cilnidipine treatment was
      performed with reperfusion after 2-h occlusion. Western blots and
      immunohistochemistry were also performed after 24-h occlusion. Initial infarct
      volume on diffusion-weighted MRI was not different between the cilnidipine group
      and the control group; however, fluid-attenuated inversion recovery MRI at 24 h
      showed significantly reduced infarct volume in the cilnidipine group compared
      with the control group. Cilnidipine treatment significantly decreased the number
      of triphosphate nick end labeling-positive cells compared to the control group.
      Western blot and immunohistochemistry showed increased expression of
      phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase-3beta, and
      Bcl-2 and decreased expression of Bax and cleaved caspase-3. These results
      suggest that cilnidipine, which is used for the treatment of hypertension, has
      neuroprotective effects in the ischemic brain through activation of the PI3K
      pathway. We investigated whether cilnidipine has neuroprotective effects on
      ischemic stroke in an animal model. We have demonstrated that the neuroprotective
      effect of cilnidipine is associated with the activation of the PI3K pathway.
      Considering the daily use of antihypertensive drugs for patients with
      hypertension, cilnidipine could be beneficial for patients with ischemic stroke. 

PMID- 26222280
TI  - The Relationship between Natural Park Usage and Happiness Does Not Hold in a
      Tropical City-State.
AB  - Previous studies have shown that contact with urban green spaces can produce
      positive effects on people's stress, health and well-being levels. However, much
      of this research has been conducted in the temperate regions of Europe or North
      America. Additionally, most studies have only compared the effects of urban and
      natural areas on health and well-being, but not made a finer distinction between
      different types of urban green spaces. We tested the relationship between well
      being and the access or use of different types of green spaces among young adults
      in Singapore, a tropical city-state. The results showed that extraversion and
      emotional stability increased subjective well-being, positive affect and life
      satisfaction and decreased stress and negative affect. In addition, we found that
      level of physical activity increased positive affect and health problems
      increased negative affect. Neither access to green spaces nor the use of green
      spaces in Singapore significantly affected the well-being metrics considered,
      contradicting findings in the temperate regions of the world. We hypothesize that
      the differences in temperature and humidity and the higher greenery and
      biodiversity levels outside parks in Singapore could explain this phenomenon. Our
      results thus question the universality of the relationship between well-being and
      park usage and highlight the need for more research into the multifaceted effects
      of green spaces on well-being in the tropics. 

PMID- 26222281
TI  - An Auditory Illusion of Proximity of the Source Induced by Sonic Crystals.
AB  - In this work we report an illusion of proximity of a sound source created by a
      sonic crystal placed between the source and a listener. This effect seems, at
      first, paradoxical to naive listeners since the sonic crystal is an obstacle
      formed by almost densely packed cylindrical scatterers. Even when the singular
      acoustical properties of these periodic composite materials have been studied
      extensively (including band gaps, deaf bands, negative refraction, and
      birrefringence), the possible perceptual effects remain unexplored. The illusion
      reported here is studied through acoustical measurements and a psychophysical
      experiment. The results of the acoustical measurements showed that, for a certain
      frequency range and region in space where the focusing phenomenon takes place,
      the sonic crystal induces substantial increases in binaural intensity, direct-to
      reverberant energy ratio and interaural cross-correlation values, all cues
      involved in the auditory perception of distance. Consistently, the results of the
      psychophysical experiment revealed that the presence of the sonic crystal between
      the sound source and the listener produces a significant reduction of the
      perceived relative distance to the sound source. 

PMID- 26222282
TI  - The thiG Gene Is Required for Full Virulence of Xanthomonas oryzae pv. oryzae by
      Preventing Cell Aggregation.
AB  - Bacterial blight of rice is an important serious bacterial diseases of rice in
      many rice-growing regions, caused by Xanthomonas oryzae pv. oryzae (Xoo). The
      thiG gene from Xoo strain ZJ173, which is involved with thiazole moiety
      production in the thiamine biosynthesis pathway, is highly conserved among the
      members of Xanthomonas. The thiG deletion mutant displayed impaired virulence and
      growth in thiamine-free medium but maintained its normal growth rate in the rice
      tissues, indicating that the thiG gene is involved in Xoo virulence. Compared to
      the wild type strain, the formation of cell-cell aggregates was affected in thiG
      deletion mutants. Although biofilm formation was promoted, motility and migration
      in rice leaves were repressed in the thiG mutants, and therefore limited the
      expansion of pathogen infection in rice. Quorum sensing and extracellular
      substance are two key factors that contribute to the formation of cell-cell
      aggregates. Our study found that in the thiG mutant the expression of two genes,
      rpfC and rpfG, which form a two-component regulatory signal system involved in
      the regulation of biofilm formation by a second messenger cyclic di-GMP is down
      regulated. In addition, our study showed that xanthan production was not affected
      but the expression of some genes associated with xanthan biosynthesis, like gumD,
      gumE, gumH and gumM, were up-regulated in thiG mutants. Taken together, these
      findings are the first to demonstrate the role of the thiazole biosynthsis gene,
      thiG, in virulence and the formation of aggregates in Xanthomonas oryzae pv.
      oryzae. 

PMID- 26222283
TI  - Neurotropic growth factors and glycosaminoglycan based matrices to induce
      dopaminergic tissue formation.
AB  - Current cell replacement therapies in Parkinson's disease (PD) are limited by low
      survival of transplanted cell and lacking regeneration of neuronal circuitries.
      Therefore, bioartificial cell carriers and growth/differentiation factors are
      applied to improve the integration of transplants and maximize newly generated
      and/or residual dopaminergic function. In this work, biohybrid poly(ethylene
      glycol) (starPEG)-heparin hydrogels releasing fibroblast growth factor 2 (FGF-2)
      and glial-derived neurotrophic factor (GDNF) were used to trigger dopaminergic
      tissue formation by primary murine midbrain cells in vitro. Matrix-delivered FGF
      2 enhanced cell viability while release of GDNF had a pro-neuronal/dopaminergic
      effect. Combined delivery of both factors from the glycosaminoglycan-based
      matrices resulted in a tremendous improvement in survival and maturation capacity
      of dopaminergic neurons as obvious from tyrosine hydroxylase expression and
      neurite outgrowth. The reported data demonstrate that glycosaminoglycan-based
      hydrogels can facilitate the administration of neurotrophic factors and are
      therefore instrumental in potential future treatments of PD. 

PMID- 26222284
TI  - pH-sensitive polymer-liposome-based antigen delivery systems potentiated with
      interferon-gamma gene lipoplex for efficient cancer immunotherapy.
AB  - Potentiation of pH-sensitive liposome-based antigen carriers with IFN-gamma gene
      lipoplexes was attempted to achieve efficient induction of tumor-specific
      immunity. 3-Methylglutarylated poly(glycidol) (MGluPG)-modified liposomes and
      cationic liposomes were used, respectively, for the delivery of antigenic protein
      ovalbumin (OVA) and IFN-gamma-encoding plasmid DNA (pDNA). The MGluPG-modified
      liposomes and the cationic liposome-pDNA complexes (lipoplexes) formed hybrid
      complexes via electrostatic interactions after their mixing in aqueous solutions.
      The hybrid complexes co-delivered OVA and IFN-gamma-encoding pDNA into DC2.4
      cells, a murine dendritic cell line, as was the case of MGluPG-modified liposomes
      for OVA or the lipoplexes for pDNA. Both the lipoplexes and the hybrid complexes
      transfected DC2.4 cells and induced IFN-gamma protein production, but
      transfection activities of the hybrid complexes were lower than those of the
      parent lipoplexes. Subcutaneous administration of hybrid complexes to mice
      bearing E.G7-OVA tumor reduced tumor volumes, which might result from the
      induction of OVA-specific cytotoxic T lymphocytes (CTLs). However, the hybrid
      complex-induced antitumor effect was the same level of the MGluPG-modified
      liposome-mediated antitumor immunity. In contrast, an extremely strong antitumor
      immune response was derived when these liposomes and lipoplexes without
      complexation were injected subcutaneously at the same site of tumor-bearing mice.
      Immunohistochemical analysis of tumor sections revealed that immunization through
      the liposome-lipoplex combination promoted the infiltration of CTLs to tumors at
      an early stage of treatment compared with liposomes, resulting in strong
      therapeutic effects. 

PMID- 26222285
TI  - Spatio-temporally controlled transfection by quantitative injection into a single
      cell.
AB  - Transfection-based cellular control has been widely used in biology; however,
      conventional transfection methods cannot control spatio-temporal differences in
      gene expression or the quantity of delivered materials such as external DNA or
      RNA. Here, we present a non-viral and spatio-temporally controlled transfection
      technique of a quantitative injection into a single cell. DNA was quantitatively
      injected into a single cell at a desired location and time, and the optimal gene
      delivery and expression conditions were determined based on the amount of the
      delivered DNA and the transfection efficacy. Interestingly, an injection of 1500
      DNAs produced an about average 30% gene expression efficiency, which was the
      optimal condition, and gene expression was sustained for more than 14 days. In a
      single cell, fluorescent intensity and polymerase chain reaction (PCR) results
      were compared for the quantity of gene expression. The high coincidence of both
      results suggests that the fluorescence intensity can reveal gene expression level
      which was investigated by PCR. In addition, 3 multiple DNA genes were
      successfully expressed in a single cell with different ratio. Overall, these
      results demonstrate that spatio-temporally controlled transfection by
      quantitative transfection is a useful technique for regulating gene expression in
      a single cell, which suggests that this technique may be used for stem cell
      research, including the creation of induced pluripotent stem (iPS) cells. 

PMID- 26222286
TI  - Impact of surface chemistry and topography on the function of antigen presenting
      cells.
AB  - Antigen presenting cells (APCs) such as macrophages and dendritic cells (DCs)
      play a crucial role in orchestrating immune responses against foreign materials.
      The activation status of APCs can determine the outcome of an immune response
      following implantation of synthetic materials, towards either healing or
      inflammation. A large range of biomaterials are used in the fabrication of
      implantable devices and drug delivery systems. These materials will be in close
      contact with APCs and characteristics such as surface chemistry and topography
      may have a critical role in initiating pro- or anti-inflammatory immune
      responses. Controlling biomaterial surface attributes provides a powerful tool
      for modulating the phenotype and function of immune cells with the aim of
      reducing detrimental pro-inflammatory responses and promoting beneficial healing
      responses. In this article, we review recent literature on how biomaterial
      surface topography and chemistry can modulate APC populations towards distinct
      pro- or anti-inflammatory phenotypes with specific examples of how these
      properties can be used to control host response in vivo. Topographical and/or
      chemical design of biomaterial surfaces with respect to the APC responses can
      pave the way for a new generation of 'cell instructive' materials with
      immunomodulatory properties with a wide range of clinical applications. 

PMID- 26222287
TI  - Hemoglobin-mediated synthesis of PEDOT:PSS: enhancing conductivity through
      biological oxidants.
AB  - Hemoglobin- and catalase-polymerized PEDOT: PSS were characterized by X-ray
      photoelectron spectroscopy, visible and near-IR spectroscopy, FTIR, and ESR.
      Hemoglobin-polymerized PEDOT: PSS possesses bipolarons, while catalase
      polymerized PEDOT: PSS is dominated by polarons. Use of heme-bound iron as an
      oxidant yields PEDOT: PSS with conductivity of 19.5 S cm(-1) in a single-step
      aqueous reaction.

PMID- 26222288
TI  - Insight into the efficient transfection activity of a designed low aggregated
      magnetic polyethyleneimine/DNA complex in serum-containing medium and the
      application in vivo.
AB  - A designed low aggregated magnetic polyethyleneimine/DNA (MPD-cc) complex showed
      efficient transfection in serum-containing medium for PEI-mediated gene
      transfection in vitro and in vivo, but the mechanism remains unclear. The present
      study provides an insight into the extracellular and intracellular fates of the
      magnetic gene complexes, evaluates their transfection efficiency and body
      distribution after systemic administration assisted by fluorescent imaging
      technology. The PEI cationic complexes in our study switched to be negatively
      charged in the serum-containing medium due to protein corona formation, and the
      complexes displayed negligible aggregation from transmission electron microscopy
      observation and dynamic light scattering analysis. However, the SDS
      polyacrylamide gel electrophoresis (SDS-PAGE) showed that less protein was
      adsorbed on the magnetic gene complexes during a 10 min magnetofection compared
      with that associated with traditional polyethyleneimine/DNA (PD) complexes after
      a long-term (4 h) incubation. In terms of cellular uptake and internalization
      evaluation by flow cytometry, magnetofection with our designed MPD-cc complexes
      showed obvious superiority in the presence of serum, compared to traditional
      transfection (PD complexes). Moreover, confocal laser scanning microscopy
      revealed that after internalization, fewer MPD-cc with magnetofection were
      trapped in the endosome and more found in the nucleus compared to the PD and MPD
      cc without the magnetic field. Putting these facts together, we conclude that
      magnetofection by the designed MPD-cc complexes facilitates many processes of
      transfection, including less protein adsorption, efficient cellular sedimentation
      and internalization, as well as endosomal escape and nuclear import. In the near
      infrared imaging study, it was observed that the accumulation of complexes in
      tumors by magnetic capture was enhanced in vivo. All of these improved in vitro
      and in vivo functions contributed to a 5-fold enhancement in magnetofection via
      intravenous delivery. 

PMID- 26222289
TI  - Multicomponent 5-fluorouracil loaded PAMAM stabilized-silver nanocomposites
      synergistically induce apoptosis in human cancer cells.
AB  - Herein, we report the development of a poly(amidoamine) (PAMAM) dendrimer based
      multicomponent therapeutic agent for in vitro cancer therapy applications. In
      this approach, Generation 5 (G5) PAMAM dendrimers stabilizing silver nanoparticle
      surface (DsAgNPs) were used to encapsulate anticancer drug 5-fluorouracil (5-FU)
      to attain synergism in cancer cells. 5-FU loaded DsAg nanocomposites (5
      FU@DsAgNCs) were characterized by UV-visible spectroscopy, transmission electron
      microscopy, X-ray diffraction, and nuclear magnetic resonance measurements. In
      vitro release studies certify the sustained release of 5-FU from nanocomposites.
      5-FU@DsAgNCs were found to elicit a synergistic antiproliferative effect in A549
      (human lung cancer) and MCF-7 (human breast cancer) cells with IC50 of 5 MUg mL(
      1) and 1.5 MUg mL(-1), and combination index (CI) values of 0.242 and 0.178,
      respectively. Atomic absorption spectroscopic analyses indicated higher cellular
      uptake of Ag in MCF-7 than that in A549 cancer cells. Nuclear and morphological
      alterations, typical of apoptosis induction, were revealed by fluorescence and
      scanning electron microscopy imaging. An increment in reactive oxygen species
      (ROS) levels was measured; this indicated the induction of oxidative stress in
      both 5-FU@DsAgNC treated cell types. Taken together, the apoptotic effects of 5
      FU@DsAgNC were more prominent in MCF-7 than in A549 cancer cells. Finally, gene
      expression studies suggested triggering of the p53 mediated caspase signalling
      gene cascade in 5-FU@DsAgNC treated cells. The strategy to use dendrimer
      technology to design multicomponent 5-FU@DsAgNCs is quite promising for
      simultaneous delivery of 5-FU and DsAgNPs to achieve synergistic anticancer
      effects. 

PMID- 26222290
TI  - IL-12 involvement in myogenic differentiation of C2C12 in vitro.
AB  - Recently, the extracellular microenvironment has been shown to be critical for
      the correct differentiation of stem cells to specific tissues. Many factors,
      including physical (e.g. biomaterial stiffness and topography) and biological (as
      growth factors, cytokines and chemokines) components, cooperate to create an
      ideal microenvironment for muscle stem cells, with many of these factors having
      been widely investigated. We previously demonstrated that the use of non
      proliferating muscle-specific and unrelated cells as feeder layers for skeletal
      muscle progenitor cell differentiation resulted in significant differences in the
      ability to form myotubes, suggesting the importance of biological factors in
      myogenic differentiation. In this study, we investigated the biological factors
      involved in this process, analyzing the expression profile of 84 genes coding for
      cytokines and chemokines. We successfully identified a novel role for the
      cytokine IL-12 in the myogenic differentiation of C2C12 mouse skeletal muscle
      cells. Experiments involving the overexpression or silencing of the IL-12 gene in
      C2C12 showed that IL-12 enhanced the myogenic differentiation process. Moreover,
      when IL-12 was overexpressed in non-biologically related feeder cells, the new co
      culture system was able to improve myogenic differentiation of C2C12 seeded on
      top. Although IL-12 is known to be a cytokine involved in inflammatory responses,
      it also appears to be involved in the myogenic differentiation process, acting as
      a positive regulator of this mechanism. This fact is expected to prove to be
      important for the development of functional biomaterials. 

PMID- 26222291
TI  - Tumor extracellular acidity activated "off-on" release of bortezomib from a
      biocompatible dendrimer.
AB  - A nanoparticle with a specific response to tumor extracellular acidity provides a
      new option in the design of tumor-targeted delivery systems. In this study, we
      report such a pH-responsive polymer which realizes an "off-on" release of
      bortezomib in tumor acidic microenvironments. A dendrimer surface is grafted with
      a neutral shell to reduce its cellular uptake, and its interior is functionalized
      with catechol moieties. An anticancer drug, bortezomib, is loaded within the
      dendrimer interior via a boronate-catechol interaction. The bortezomib-loaded
      dendrimer is non-toxic to a number of cells under physiological conditions, but
      kills most of the cells in slightly acidic microenvironments. In vivo studies
      further prove that the bortezomib-loaded dendrimer significantly inhibits tumor
      growth while causing minimal systemic toxicity to the animals. Since there are a
      number of potent anticancer drugs containing the boronate structure, the
      polymeric vector in this study provides a versatile scaffold to design pH
      responsive drug carriers for chemotherapy. 

PMID- 26222292
TI  - Cell membrane-inspired polymeric micelles as carriers for drug delivery.
AB  - In cancer therapy, surface engineering of drug delivery systems plays an
      essential role in their colloidal stability, biocompatibility and prolonged blood
      circulation. Inspired by the cell membrane consisting of phospholipids and
      glycolipids, a zwitterionic phosphorylcholine functionalized chitosan
      oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head
      groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to
      lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA
      copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a
      hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers,
      showing excellent stability under extreme conditions including protein containing
      media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully
      entrapped into polymeric micelles through the hydrophobic interaction between DOX
      and SA segments. After fast internalization by cancer cells, sustained drug
      release from micelles to the cytoplasm and nucleus was achieved. This result
      suggests that these biomimetic polymeric micelles may be promising drug delivery
      systems in cancer therapy. 

PMID- 26222293
TI  - Hydrogen-bonding dramatically modulates the gene transfection efficacy of surface
      engineered dendrimers.
AB  - Dendrimers have shown great promise in the design of efficient gene vectors.
      However, high transfection efficacy is usually associated with serious
      cytotoxicity for these cationic polymers. Here, we report a facile strategy to
      prepare surface-engineered dendrimers with a dramatic transfection efficacy and
      reduced cytotoxicity. Surface-engineered dendrimers with multiple hydrogen
      bonding ligands such as guanamine and nucleobase derivatives show superior
      efficacy and low cytotoxicity on commonly used cells as well as 3D tumor
      spheroids to representative transfection reagents such as Lipofectamine 2000.
      Complementary multiple hydrogen bonding interactions between the modified ligands
      and DNA nucleobases play essential roles in efficient gene transfection. The
      hydrogen-bond modulation strategy represents a promising tool in the design of
      highly efficient and less cytotoxic gene materials. 

PMID- 26222294
TI  - Accelerated healing of cutaneous wounds using phytochemically stabilized gold
      nanoparticle deposited hydrocolloid membranes.
AB  - Rapid healing of dermatological wounds is of vital importance in preventing
      infection and reducing post-treatment side-effects. Here we report the
      therapeutic effects of phytochemically stabilized gold nanoparticles (pAuNPs)
      coated on a hydrocolloid membrane (HCM) for curing cutaneous wounds. Furthermore,
      the remedial effects of pAuNPs on skin regeneration and angiogenesis were
      examined using Sprague Dawley(r) (SD) rats with skin injuries after a pAuNP
      deposited hydrocolloid membrane (pAuNP-HCM) had been applied for 15 days. The
      rate of wound closure was 4 times faster in the pAuNP-HCM-treated group than in
      the gauze (GZ)- or HCM-treated groups in the first 5 days. Moreover, wound widths
      in the pAuNP-HCM-treated group were significantly reduced after 5-15 days of
      treatment following the injury, compared with the other groups. In addition, a
      significant increase in collagen expression and a decrease in matrix
      metalloproteinase (MMP)-1 expression and transforming growth factor (TGF-beta1)
      concentration were observed in the pAuNP-HCM-treated group on day 5. Wound tissue
      applied with the pAuNP-HCM showed enhancement of vascular endothelial growth
      factor (VEGF), angiopoietin 1 (Ang-1), and angiopoietin 2 (Ang-2) expression.
      Furthermore, the activity of superoxide dismutases (SODs) was significantly
      increased in the skin tissue of the pAuNP-HCM-treated group, compared with the GZ
      or HCM-treated groups. It is probable that the accelerated process of wound
      healing in the injured skin of SD rats via pAuNP-HCM results from the synergistic
      regulation of angiogenesis and connective tissue formation, as well as the
      stimulation of antioxidant effects. 

PMID- 26222295
TI  - Epitope topography controls bioactivity in supramolecular nanofibers.
AB  - Incorporating bioactivity into artificial scaffolds using peptide epitopes
      present in the extracellular matrix (ECM) is a well-known approach. A common
      strategy has involved epitopes that provide cells with attachment points and
      external cues through interaction with integrin receptors. Although a variety of
      bioactive sequences have been identified so far, less is known about their
      optimal display in a scaffold. We report here on the use of self-assembled
      peptide amphiphile (PA) nanofiber matrices to investigate the impact of spatial
      presentation of the fibronectin derived epitope RGDS on cell response. Using one,
      three, or five glycine residues, RGDS epitopes were systematically spaced out
      from the surface of the rigid nanofibers. We found that cell morphology was
      strongly affected by the separation of the epitope from the nanofiber surface,
      with the longest distance yielding the most cell-spreading, bundling of actin
      filaments, and a round-to-polygonal transformation of cell shape. Cell response
      to this type of epitope display was also accompanied with activated integrin
      mediated signaling and formation of stronger adhesions between cells and
      substrate. Interestingly, unlike length, changing the molecular flexibility of
      the linker had minimal influence on cell behavior on the substrate for reasons
      that remain poorly understood. The use in this study of high persistence length
      nanofibers rather than common flexible polymers allows us to conclude that
      epitope topography at the nanoscale structure of a scaffold influences its
      bioactive properties independent of epitope density and mechanical properties. 

PMID- 26222296
TI  - Enhanced cellular uptake of engineered spider silk particles.
AB  - Drug delivery systems allow tissue/cell specific targeting of drugs in order to
      reduce total drug amounts administered to an organism and potential side effects
      upon systemic drug delivery. Most drug delivery systems are polymer-based, but
      the number of possible materials is limited since many commercially available
      polymers induce allergic or inflammatory responses or lack either
      biodegradability or the necessary stability in vivo. Spider silk proteins
      represent a new class of (bio)polymers that can be used as drug depots or drug
      delivery systems. The recombinant spider silk protein eADF4(C16), which can be
      processed into different morphologies such as particles, films, or hydrogels, has
      been shown to fulfil most criteria necessary for its use as biomaterial. Further,
      eADF4(C16) particles have been shown to be well-suited for drug delivery. Here, a
      new method was established for particle production to reduce particle size and
      size distribution. Importantly, cellular uptake of these particles was shown to
      be poor in HeLa cells. Therefore, variants of eADF4(C16) with inversed net charge
      or incorporated cell penetrating peptides and receptor interacting motifs were
      tested, showing much better cellular uptake. Interestingly, uptake of all silk
      variant particles was mainly achieved by clathrin-mediated endocytosis. 

PMID- 26222297
TI  - Social defeat protocol and relevant biomarkers, implications for stress response
      physiology, drug abuse, mood disorders and individual stress vulnerability: a
      systematic review of the last decade.
AB  - INTRODUCTION: Social defeat (SD) in rats, which results from male intraspecific
      confrontations, is ethologically relevant and useful to understand stress effects
      on physiology and behavior. METHODS: A systematic review of studies about
      biomarkers induced by the SD protocol and published from 2002 to 2013 was carried
      out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The
      search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers,
      and transcriptional factors. RESULTS: Classical and recently discovered
      biomarkers were found to be relevant in stress-induced states. Findings were
      summarized in accordance to the length of exposure to stress: single, repeated,
      intermittent and continuous SD. This review found that the brain-derived
      neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with
      glucocorticoids and catecholamines, BDNF seems to be important in understanding
      stress physiology. CONCLUSION: The SD model provides a relevant tool to study
      stress response features, development of addictive behaviors, clinic depression
      and anxiety, as well as individual differences in vulnerability and resilience to
      stress.

PMID- 26222298
TI  - Predictors of discharge in child psychoanalytic psychotherapy.
AB  - INTRODUCTION: This empirical study was based on the analysis of the results of a
      study about dropout predictors among in child psychoanalytic psychotherapy. The
      objectives were to characterize the sample of children discharged from
      psychoanalytic psychotherapy, examine the association between sociodemographic/
      clinical variables and child psychoanalytic psychotherapy discharge, and
      determine predictors of discharge in child psychoanalytic psychotherapy. METHOD:
      This quantitative, descriptive and retrospective study analyzed the clinical
      records of 600 children treated in three institutions that offer graduate courses
      in psychoanalytic psychotherapy in Porto Alegre, Brazil. RESULTS: The analysis of
      clinical records revealed that 24.2% of the child patients were discharged from
      treatment. Neurological assessment and treatment duration were predictors of
      discharge in child psychoanalytic psychotherapy. CONCLUSION: The predictors of
      discharge and dropout may coincide, but they are not the same. In this sample,
      the construction of the therapeutic alliance and the understanding of the reasons
      why children need psychotherapy by their parents or guardians may explain our
      findings.

PMID- 26222299
TI  - Moderators of the association between discrimination and alcohol consumption:
      findings from a representative sample of Brazilian university students.
AB  - INTRODUCTION: Few studies about discrimination and patterns of alcohol
      consumption among youth populations have been conducted outside the United States
      addressing different types of discriminatory experiences, in addition to racially
      motivated events. This study investigated moderators of the association between
      discrimination attributed to single and multiple reasons and patterns of alcohol
      consumption. METHODS: This cross-sectional study enrolled a representative sample
      (n = 1,264) of undergraduate students from Florianopolis, southern Brazil, in
      2013. Analyses included adjustment of associations for covariates in ordinal
      logistic regression models and the examination of effect modification by common
      mental disorders, year of study and age. RESULTS: Discrimination was reported by
      65.8% of the students, and alcohol consumption, by 80.0%. Over half of the
      students reported being discriminated against for two or more reasons. The odds
      of alcohol-related problems were higher among lastyear students that reported
      discrimination (odds ratio [OR] = 1.9, 95% confidence interval [95%CI] 1.0-3.4)
      or multiple reasons for being discriminated against (OR = 2.3, 95%CI 1.3- 4.3),
      when compared to first-year students that did not report discrimination. For the
      whole sample, there were no associations between discrimination, discrimination
      attributed to multiple reasons and patterns of alcohol consumption (OR = 1.0,
      95%CI 0.8-1.4; and OR = 0.9, 95%CI 0.5-1.6). CONCLUSIONS: The effects of
      discrimination on the patterns of alcohol consumption are seen at a critical
      period in university life, specifically during the completion of undergraduate
      studies.

PMID- 26222300
TI  - Drug interactions between antineoplastic and antidepressant agents: analysis of
      patients seen at an oncology clinic at a general hospital.
AB  - OBJECTIVES: To determine the prevalence of depressive symptoms among oncology
      patients and identify simultaneous use of antineoplastic and antidepressant
      agents. METHODS: This was a cross-sectional study that interviewed 56 oncology
      patients using two data collection instruments: a questionnaire covering clinical
      and sociodemographic data and the Beck Depression Inventory-II (BDI-II), for
      assessment of depressive symptoms. For data analysis, descriptive statistics were
      used to determine the prevalence of depressive symptoms and the chi-square test
      was used to evaluate associations between sociodemographic and clinical variables
      and depressive symptoms. RESULTS: A 26.7% (15 patients) prevalence of depression
      was detected. Just eight of these 15 patients (53.3%) were receiving treatment
      for depression. In the sample as a whole, 13 of the patients interviewed (23.2%)
      were taking antidepressants and 11 of these 13 patients (19.6%) were taking
      antidepressive and antineoplastic agents simultaneously. A total of five (8.9% of
      the sample) contraindicated drug interactions were detected. CONCLUSIONS:
      Depressive symptoms are more prevalent among cancer patients than in the general
      population, but they are generally under-diagnosed and under-treated.
      Simultaneous use of antidepressant and antineoplastic agents is common and so, in
      order to reduce the number of harmful adverse effects, possible drug interactions
      must be identified before antidepressants are prescribed to cancer patients.

PMID- 26222301
TI  - Cross-cultural adaptation to Portuguese of a measure of satisfaction with
      participation of the Patient-Reported Outcomes Measurement Information System
      (PROMIS(r)).
AB  - BACKGROUND: Mental disorders often impair functioning in several areas of life
      and lead to unhappiness and suffering that may affect health-related quality of
      life (HRQoL). Satisfaction with participation is an indicator of HRQoL, and its
      measurement by patients reflects the impact of disease on their social, emotional
      and professional life. The Patient-Reported Outcomes Measurement Information
      System (PROMIS(r)) offers an item bank based on item response theory. This system
      provides efficient, reliable and valid self-report instruments of satisfaction
      with participation, a measure that is both scarce and useful in the assessment of
      mental disorder outcomes. OBJECTIVE: To cross-culturally adapt the PROMIS(r)
      satisfaction with participation item bank to Portuguese. METHODS: Cross-cultural
      adaptation followed the Functional Assessment of Chronic Illness Therapy (FACIT)
      multilingual translation method and was achieved through steps of forward and
      backward translations, review by bilingual experts (one of them a native of
      Portugal) and pretesting in a group of 11 adult native Brazilians. Instrument
      adaptation followed a universal approach to translation, with harmonization
      across languages. RESULTS: Equivalence of meaning was achieved. As two of the 26
      translated items, which asked about leisure and social activities, were not
      understood by less educated participants, an explanation in parentheses was added
      to each item, and the problem was solved. All items were appropriate and did not
      cause embarrassment to the participants. CONCLUSIONS: The satisfaction with
      participation item bank is culturally and linguistically suitable to be used in
      Brazil. After the pretest is applied in Portugal and in other Portuguese-speaking
      countries, the same instrument will be ready to be used in multinational studies.

PMID- 26222302
TI  - Where does her mood come from? An organic approach to a once functional patient.
AB  - OBJECTIVE: To report the rare development of manic symptoms in a patient with
      schizophrenia and discuss its differential diagnosis. CASE DESCRIPTION:
      Diagnostic criteria were based on the International Classification of Diseases,
      10th edition (ICD-10). A 63-year-old female (diagnosed with schizophrenia since
      she was 28) was brought to the emergency room with symptoms consistent with manic
      episode and physical examination suggestive of thyrotoxicosis. Graves' disease
      was confirmed by subsequent laboratory tests. She was treated successfully with
      radioiodine ablation, leading to full remission of manic symptoms. COMMENTS:
      Schizophrenia is a chronic disease that affects about 1% of the population
      worldwide. The main symptoms of the disorder are altered affection, delusions,
      and hallucinations. Graves' disease is an autoimmune condition in which
      antibodies increase the production and release of thyroid hormones. There are
      reports about the development of mood symptoms in patients with Graves' disease
      that remit with adequate treatment.

PMID- 26222303
TI  - The role of inflammation in schizophrenia: an overview.

PMID- 26222305
TI  - Interleukin-23 Receptor Gene Polymorphism May Enhance Expression of the IL-23
      Receptor, IL-17, TNF-alpha and IL-6 in Behcet's Disease.
AB  - PURPOSE: Recent studies identified an association between Behcet's disease (BD)
      and the IL-23R gene polymorphism (rs17375018) in different populations. This
      study examined whether this IL-23R gene polymorphism is associated with enhanced
      inflammatory responses. METHODS: We recruited 27 BD patients and 32 controls with
      three genotypes. Peripheral blood mononuclear cells (PBMCs) were seeded with or
      without anti-CD3 and CD28. Cells were incubated for 24 hours, and then
      supernatants were collected and stored at -20?C until analyzed. Levels of
      interferon (IFN)-gamma, tissue necrosis factor (TNF)-alpha, interleukin (IL)-17
      and IL-6 were detected by ELISA. IL-23R expression was assessed by quantitative
      real-time polymerase chain reaction (RT-PCR). RESULTS: The expression of IL-23R
      was significantly higher in both BD patients and healthy controls with the GG
      genotype compared to the AG and AA genotype with anti-CD3 and CD28 stimulation
      (all P-value < 0.05). Among the PBMCs cultured with anti-CD3 and CD28
      stimulation, there was an elevated secretion of TNF-alpha, IL-6 and IL-17 in BD
      patients and healthy controls with the GG genotype. However, there was no
      significant change in secretion of IFN- gamma in BD patients and healthy controls
      among the genotype of this IL-23R gene polymorphism. CONCLUSIONS: The results
      suggest that the GG genotype of the rs17375018 variant in the IL-23R gene
      enhances pro-inflammatory cytokine responses.

PMID- 26222304
TI  - Immunogenicity of the Plasmodium falciparum PfEMP1-VarO Adhesin: Induction of
      Surface-Reactive and Rosette-Disrupting Antibodies to VarO Infected Erythrocytes.
AB  - Adhesion of Plasmodium falciparum-infected red blood cells (iRBC) to human
      erythrocytes (i.e. rosetting) is associated with severe malaria. Rosetting
      results from interactions between a subset of variant PfEMP1 (Plasmodium
      falciparum erythrocyte membrane protein 1) adhesins and specific erythrocyte
      receptors. Interfering with such interactions is considered a promising
      intervention against severe malaria. To evaluate the feasibility of a vaccine
      strategy targetting rosetting, we have used here the Palo Alto 89F5 VarO
      rosetting model. PfEMP1-VarO consists of five Duffy-Binding Like domains (DBL1-5)
      and one Cysteine-rich Interdomain Region (CIDR1). The binding domain has been
      mapped to DBL1 and the ABO blood group was identified as the erythrocyte
      receptor. Here, we study the immunogenicity of all six recombinant PfEMP1-VarO
      domains and the DBL1- CIDR1 Head domain in BALB/c and outbred OF1 mice. Five
      readouts of antibody responses are explored: ELISA titres on the recombinant
      antigen, VarO-iRBC immunoblot reactivity, VarO-iRBC surface-reactivity, capacity
      to disrupt VarO rosettes and the capacity to prevent VarO rosette formation. For
      three domains, we explore influence of the expression system on antigenicity and
      immunogenicity. We show that correctly folded PfEMP1 domains elicit high antibody
      titres and induce a homogeneous response in outbred and BALB/c mice after three
      injections. High levels of rosette-disrupting and rosette-preventing antibodies
      are induced by DBL1 and the Head domain. Reduced-alkylated or denatured proteins
      fail to induce surface-reacting and rosette-disrupting antibodies, indicating
      that surface epitopes are conformational. We also report limited cross-reactivity
      between some PfEMP1 VarO domains. These results highlight the high immunogenicity
      of the individual domains in outbred animals and provide a strong basis for a
      rational vaccination strategy targeting rosetting. 

PMID- 26222306
TI  - Regulation of Spermatogenic Cell T-Type Ca(2+) Currents by Zn(2+): Implications
      in Male Reproductive Physiology.
AB  - Zn(2+) is a trace metal which is important for spermatogenesis progression; its
      deficiency causes atrophy or malignant growth of the testis. Although testis,
      epididymis, and prostate contain high Zn(2+) concentrations, the molecular
      entities which are modulated by this metal are still under study. Interestingly,
      spermatogenic cells mainly express CaV 3.2-encoded T-type Ca(2+) currents (ICaT)
      which are positively or negatively modulated by Zn(2+) in other tissues. To
      explore whether ICaT could be regulated by Zn(2+) and albumin, its main
      physiological carrier, we performed whole cell electrophysiological recordings of
      spermatogenic cell ICaT in the absence or presence of different Zn(2+)
      concentrations. Zn(2+) decreased ICaT in a concentration-dependent manner (IC50 
      = 2 MUM) and this inhibition could only be completely removed in presence of
      albumin. Differently to previous reports, ICaT did not show a tonic inhibition by
      Zn(2+) . Further analysis showed that Zn(2+) did not affect the voltage
      dependency or the kinetics of current activation, but right shifted the steady
      state inactivation curve and slowed inactivation and deactivation kinetics.
      Recovery from inactivation was also altered. However, these apparent alterations
      in gating properties are not enough to explain the strong ICaT reduction. Using
      non-stationary fluctuation analysis, we found that Zn(2+) mainly reduced the
      number of available Ca(2+) channels without changing the single channel current
      amplitude. ICaT modulation by Zn(2+) could be relevant for spontaneous Ca(2+)
      oscillations during spermatogenesis and in pathophysiological conditions such as
      diabetes.

PMID- 26222307
TI  - An Economic Framework of Microbial Trade.
AB  - A large fraction of microbial life on earth exists in complex communities where
      metabolic exchange is vital. Microbes trade essential resources to promote their
      own growth in an analogous way to countries that exchange goods in modern
      economic markets. Inspired by these similarities, we developed a framework based
      on general equilibrium theory (GET) from economics to predict the population
      dynamics of trading microbial communities. Our biotic GET (BGET) model provides
      an a priori theory of the growth benefits of microbial trade, yielding several
      novel insights relevant to understanding microbial ecology and engineering
      synthetic communities. We find that the economic concept of comparative advantage
      is a necessary condition for mutualistic trade. Our model suggests that microbial
      communities can grow faster when species are unable to produce essential
      resources that are obtained through trade, thereby promoting metabolic
      specialization and increased intercellular exchange. Furthermore, we find that
      species engaged in trade exhibit a fundamental tradeoff between growth rate and
      relative population abundance, and that different environments that put greater
      pressure on group selection versus individual selection will promote varying
      strategies along this growth-abundance spectrum. We experimentally tested this
      tradeoff using a synthetic consortium of Escherichia coli cells and found the
      results match the predictions of the model. This framework provides a foundation
      to study natural and engineered microbial communities through a new lens based on
      economic theories developed over the past century. 

PMID- 26222309
TI  - Introduction of a co-resonant detection concept for mechanical oscillation-based
      sensors.
AB  - Micro- and nanoelectromechanical oscillators driven at or close to their
      resonance frequency are used as sensors in many fields of science and technology.
      A decrease in the oscillator's effective spring constant and/or mass holds great
      potential for an increase in the sensor's sensitivity. This is usually
      accompanied by a reduction in spatial dimensions, which in most cases requires
      more complex detection methods. By analyzing the complex behavior of a simple
      asymmetric coupled harmonic oscillator model we propose a novel sensor concept
      which combines the advantages of bigger and smaller oscillators, i.e. ease of
      detection and high sensitivity. The concept is based on matching the resonance
      frequencies of two otherwise very different oscillators. To support our
      theoretical considerations, we present an experimental implementation of such a
      sensor and respective experimental data, verifying a substantial signal
      enhancement by several orders of magnitude. 

PMID- 26222308
TI  - CDK8-Cyclin C Mediates Nutritional Regulation of Developmental Transitions
      through the Ecdysone Receptor in Drosophila.
AB  - The steroid hormone ecdysone and its receptor (EcR) play critical roles in
      orchestrating developmental transitions in arthropods. However, the mechanism by
      which EcR integrates nutritional and developmental cues to correctly activate
      transcription remains poorly understood. Here, we show that EcR-dependent
      transcription, and thus, developmental timing in Drosophila, is regulated by CDK8
      and its regulatory partner Cyclin C (CycC), and the level of CDK8 is affected by
      nutrient availability. We observed that cdk8 and cycC mutants resemble EcR
      mutants and EcR-target genes are systematically down-regulated in both mutants.
      Indeed, the ability of the EcR-Ultraspiracle (USP) heterodimer to bind to
      polytene chromosomes and the promoters of EcR target genes is also diminished.
      Mass spectrometry analysis of proteins that co-immunoprecipitate with EcR and USP
      identified multiple Mediator subunits, including CDK8 and CycC. Consistently,
      CDK8-CycC interacts with EcR-USP in vivo; in particular, CDK8 and Med14 can
      directly interact with the AF1 domain of EcR. These results suggest that CDK8
      CycC may serve as transcriptional cofactors for EcR-dependent transcription.
      During the larval-pupal transition, the levels of CDK8 protein positively
      correlate with EcR and USP levels, but inversely correlate with the activity of
      sterol regulatory element binding protein (SREBP), the master regulator of
      intracellular lipid homeostasis. Likewise, starvation of early third instar
      larvae precociously increases the levels of CDK8, EcR and USP, yet down-regulates
      SREBP activity. Conversely, refeeding the starved larvae strongly reduces CDK8
      levels but increases SREBP activity. Importantly, these changes correlate with
      the timing for the larval-pupal transition. Taken together, these results suggest
      that CDK8-CycC links nutrient intake to developmental transitions (EcR activity)
      and fat metabolism (SREBP activity) during the larval-pupal transition. 

PMID- 26222310
TI  - The GSTA1 polymorphism and cyclophosphamide therapy outcomes in lupus nephritis
      patients.
AB  - Pulsed low-dose cyclophosphamide (CTX) therapy has become a very effective
      approach in improving the clinical outcomes of lupus nephritis (LN) patients.
      However, variations of CTX therapeutic outcomes in LN patients are incompletely
      understood. We investigated the contributions of known allelic variants to CTX
      therapy outcomes in 77 LN patients. Then, 22 out of the 77 patients were randomly
      enrolled to evaluate the pharmacokinetic profiles. LN patients with a GSTA1*A
      mutation (CT heterozygous) had more risk of non-remission (44% vs. 20%, P=0.005).
      Pharmacokinetic data indicated that patients with a GSTA1*A heterozygous variant
      had a lower exposure to 4-hydroxycyclophosphamide (4OHCTX) compared to wild-type
      patients (AUC4OHCTX: 12.8 (9.8, 19.5) vs. 27.5 (18.1, 32.8) h mg/l, P=0.023).
      Clinical remission was significantly related to higher exposure of 4OHCTX
      (P=0.038). In conclusion, LN patients with GSTA1*A heterozygous genotypes had
      poor CTX treatment remission due to less exposure to activated metabolites of
      CTX. 

PMID- 26222312
TI  - Symptoms and Cognitive Functions in Adolescents in Relation to Mobile Phone Use
      during Night.
AB  - Many adolescents tend to leave their mobile phones turned on during night,
      accepting that they may be awakened by an incoming text message or call. Using
      self-reported and objective operator recorded mobile phone use data, we thus
      aimed to analyze how being awakened during night by mobile phone affects
      adolescents' perceived health and cognitive functions. In this cross-sectional
      study, 439 adolescents completed questionnaires about their mobile phone use
      during night, health related quality of life and possible confounding factors.
      Standardized computerized cognitive tests were performed to assess memory and
      concentration capacity. Objective operator recorded mobile phone use data was
      further collected for 233 study participants. Data were analyzed by multivariable
      regression models adjusted for relevant confounders including amount of mobile
      phone use. For adolescents reporting to be awakened by a mobile phone during
      night at least once a month the odds ratio for daytime tiredness and rapid
      exhaustibility were 1.86 (95% CI: 1.02-3.39) and 2.28 (95% CI: 0.97-5.34),
      respectively. Similar results were found when analyzing objective operator
      recorded mobile phone use data (tiredness: 1.63, 95% CI: 0.94-2.82 and rapid
      exhaustibility: 2.32, 95% CI: 1.01-5.36). The cognitive tests on memory and
      concentration capacity were not related to mobile phone use during night.
      Overall, being awakened during night by mobile phone was associated with an
      increase in health symptom reports such as tiredness, rapid exhaustibility,
      headache and physical ill-being, but not with memory and concentration capacity.
      Prevention strategies should focus on helping adolescents set limits for their
      accessibility by mobile phone, especially during night. 

PMID- 26222311
TI  - Hypoxia Up-Regulates Galectin-3 in Mammary Tumor Progression and Metastasis.
AB  - The tumor microenvironment encompasses several stressful conditions for cancer
      cells such as hypoxia, oxidative stress and pH alterations. Galectin-3, a well
      studied member of the beta-galactoside-binding animal family of lectins has been
      implicated in multiple steps of metastasis as cell-cell and cell-ECM adhesion,
      promotion of angiogenesis, cell proliferation and resistance to apoptosis.
      However, both its aberrantly up- and down-regulated expression was observed in
      several types of cancer. Thus, the mechanisms that regulate galectin-3 expression
      in neoplastic settings are not clear. In order to demonstrate the putative role
      of hypoxia in regulating galectin-3 expression in canine mammary tumors (CMT), in
      vitro and in vivo studies were performed. In malignant CMT cells, hypoxia was
      observed to induce expression of galectin-3, a phenomenon that was almost
      completely prevented by catalase treatment of CMT-U27 cells. Increased galectin-3
      expression was confirmed at the mRNA level. Under hypoxic conditions the
      expression of galectin-3 shifts from a predominant nuclear location to
      cytoplasmic and membrane expressions. In in vivo studies, galectin-3 was
      overexpressed in hypoxic areas of primary tumors and well-established metastases.
      Tumor hypoxia thus up-regulates the expression of galectin-3, which may in turn
      increase tumor aggressiveness. 

PMID- 26222313
TI  - The enrichment of surface passive film on stainless steel during biofilm
      development in coastal seawater.
AB  - The surface passive film on UNS S30400 alloy was characterized before and after
      biofilm development under different regimes of diurnal lighting in quiescent
      flowing coastal seawater. As exemplified by atomic force microscopy, the passive
      film grew under all test conditions with conspicuous variations in morphological
      features. X-ray photon spectroscopy illustrated an enrichment of the outer film
      by iron oxide and a progressive increase in the iron oxide/chromium oxide ratio
      with lighting. Mott-Schottky plots reflected the duplex nature of the film,
      comprising an outer n-type and an inner p-type configuration. The slopes of the
      plots showed a strong decrease in donor and acceptor densities with biofilm
      coverage and lighting, thus confirming passive film growth. These results provide
      new insights that passive film enrichment is an intrinsic process under practical
      marine conditions, and show that the evolution of the passive film is a key step
      to sustained passivity and/or its breakdown by microbial mechanisms. 

PMID- 26222314
TI  - Kinetic study of the quenching reaction of singlet oxygen by seven rice bran
      extracts in ethanol solution. Development of a singlet oxygen absorption capacity
      (SOAC) assay method.
AB  - Measurements of singlet oxygen ((1)O2) quenching rates (kQ (S)) and the relative
      singlet oxygen absorption capacity (SOAC) values were performed for seven rice
      bran extracts 1-7, which contained different concentrations of antioxidants (AOs)
      (such as alpha-, beta-, gamma-, and delta-tocopherols and -tocotrienols, three
      carotenoids (lutein, beta-carotene, and zeaxanthin), and gamma-oryzanol), in
      ethanol at 35  degrees C using UV-vis spectrophotometry. The concentrations of
      four tocopherols and four tocotrienols, three carotenoids, and gamma-oryzanol
      contained in the extracts were determined using HPLC-MS/MS, UV-HPLC, and UV-vis
      absorption spectroscopy, respectively. Furthermore, comparisons of kQ (S) (Obsd.)
      values observed for the above extracts 1-7 with the sum of the product {[Formula:
      see text] [AO-i]} of the [Formula: see text] values obtained for each AO-i and
      the concentration ([AO-i]) of AO-i contained in extracts 1-7 were performed. From
      the results, it has been ascertained that the SOAC method is applicable to
      general food extracts to evaluate their (1)O2-quenching activity.

PMID- 26222315
TI  - The Esg Gene Is Involved in Nicotine Sensitivity in Drosophila melanogaster.
AB  - In humans, there is a strong correlation between sensitivity to substances of
      abuse and addiction risk. This differential tolerance to drugs has a strong
      genetic component. The identification of human genetic factors that alter drug
      tolerance has been a difficult task. For this reason and taking advantage of the
      fact that Drosophila responds similarly to humans to many drugs, and that
      genetically it has a high degree of homology (sharing at least 70% of genes known
      to be involved in human genetic diseases), we looked for genes in Drosophila that
      altered their nicotine sensitivity. We developed an instantaneous nicotine
      vaporization technique that exposed flies in a reproducible way. The amount of
      nicotine sufficient to "knock out" half of control flies for 30 minutes was
      determined and this parameter was defined as Half Recovery Time (HRT). Two fly
      lines, L4 and L70, whose HRT was significantly longer than control's were
      identified. The L4 insertion is a loss of function allele of the transcriptional
      factor escargot (esg), whereas L70 insertion causes miss-expression of the
      microRNA cluster miR-310-311-312-313 (miR-310c). In this work, we demonstrate
      that esg loss of function induces nicotine sensitivity possibly by altering
      development of sensory organs and neurons in the medial section of the
      thoracoabdominal ganglion. The ectopic expression of the miR-310c also induces
      nicotine sensitivity by lowering Esg levels thus disrupting sensory organs and
      possibly to the modulation of other miR-310c targets. 

PMID- 26222317
TI  - Synthesis, luminescence, and electrochemical studies of a new series of
      octanuclear ruthenium(II) complexes of tolylterpyridine appended
      calixresorcarenes.
AB  - A new series of octanuclear Ru(ii) complexes of tolylterpyridine appended
      calixresorcarenes [{Ru(ttpy)}8()](PF6)16 (), [{Ru(ttpy)}8()](PF6)16 (), and
      [{Ru(ttpy)}8()](PF6)16 () [ = 2,8,14,20-tetraethyl-4,6,10,12,16,18,22,24-octa(4'
      p-benzyloxy-(2,2':6',2''-terpyridinyl))calix[4]resorcarene; = 2,8,14,20
      tetraphenyl-4,6,10,12,16,18,22,24-octa(4'-p-benzyloxy-(2,2':6',2''
      terpyridinyl))calix[4]resorcarene; and = 2,8,14,20-tetra-p-tolyl
      4,6,10,12,16,18,22,24-octa(4'-p-benzyloxy-(2,2':6',2''
      terpyridinyl))calix[4]resorcarene] have been synthesized and characterized. The
      tetraethyl-, tetraphenyl-, and tetra-p-tolylcalixresorcarenes (), (), and (),
      respectively, are characterized by single crystal X-ray diffraction: () a =
      13.5771(4) A, b = 7.9566(3) A, c = 18.3912(6) A, alpha = gamma = 90 degrees ,
      beta = 103.146(2) degrees , V = 1934.69(11) A(3), Z = 2, monoclinic, P2/n; () a =
      11.9710(8) A, b = 12.7057(9) A, c = 13.8570(9) A, alpha = 94.731(2) degrees ,
      beta = 108.558(2) degrees , gamma = 106.657(2) degrees , V = 1878.9(2) A(3), Z =
      1, triclinic, P1[combining macron]; and () a = 26.076(3) A, b = 20.056(2) A, c =
      16.0193(19) A, alpha = gamma = 90 degrees , beta = 116.056(3) degrees , V =
      7526.3(14) A(3), Z = 4, monoclinic, C2/c, respectively. The octanuclear complexes
      are nonluminescent at 298 K, but exhibit (3)MLCT luminescence at 654, 649, and
      646 nm, respectively, at 77 K in acetonitrile. In the solid state at 298 K they
      exhibit (3)MLCT luminescence at 658, 658, and 665 nm, respectively. The complexes
      exhibit a monoexponential decay profile in acetonitrile and in the solid state at
      298 K. The redox active hosts containing eight [Ru(ttpy)2](2+) moieties undergo
      quasireversible one-electron oxidation at 1.25, 1.26, and 1.25 V versus Ag/Ag(+),
      respectively, in acetonitrile. The study demonstrates the versatility of the
      octanucleating calixresorcarene based ligands , , and in forming octanuclear
      Ru(ii) complexes. 

PMID- 26222316
TI  - Positron Emission Tomography (PET) Quantification of GABAA Receptors in the Brain
      of Fragile X Patients.
AB  - Over the last several years, evidence has accumulated that the GABAA receptor is
      compromised in animal models for fragile X syndrome (FXS), a common hereditary
      form of intellectual disability. In mouse and fly models, agonists of the GABAA
      receptor were able to rescue specific consequences of the fragile X mutation.
      Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X
      patients using Positron Emission Topography (PET) and [11C]flumazenil, a known
      high-affinity and specific ligand for the benzodiazepine site of GABAA receptors.
      We measured regional GABAA receptor availability in 10 fragile X patients and 10
      control subjects. We found a significant reduction of on average 10% in GABAA
      receptor binding potential throughout the brain in fragile X patients. In the
      thalamus, the brain region showing the largest difference, the GABAA receptor
      availability was even reduced with 17%. This is one of the first reports of a PET
      study of human fragile X brain and directly demonstrates that the GABAA receptor
      availability is reduced in fragile X patients. The study reinforces previous
      hypotheses that the GABAA receptor is a potential target for rational
      pharmacological treatment of fragile X syndrome. 

PMID- 26222318
TI  - Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe
      Abdominal Bloating: A Randomized, Controlled Trial.
AB  - BACKGROUND: Abdominal bloating is a common and bothersome symptom of chronic
      idiopathic constipation. The objective of this trial was to evaluate the efficacy
      and safety of linaclotide in patients with chronic idiopathic constipation and
      concomitant moderate-to-severe abdominal bloating. METHODS: This Phase 3b,
      randomized, double-blind, placebo-controlled clinical trial randomized patients
      to oral linaclotide (145 or 290 MUg) or placebo once daily for 12 weeks. Eligible
      patients met Rome II criteria for chronic constipation upon entry with an average
      abdominal bloating score >=5 (self-assessment: 0 10-point numerical rating scale)
      during the 14-day baseline period. Patients reported abdominal symptoms
      (including bloating) and bowel symptoms daily; adverse events were monitored. The
      primary responder endpoint required patients to have >=3 complete spontaneous
      bowel movements/week with an increase of >=1 from baseline, for >=9 of 12 weeks.
      The primary endpoint compared linaclotide 145 MUg vs. placebo. RESULTS: The
      intent-to-treat population included 483 patients (mean age=47.3 years,
      female=91.5%, white=67.7%). The primary endpoint was met by 15.7% of linaclotide
      145 MUg patients vs. 7.6% of placebo patients (P<0.05). Both linaclotide doses
      significantly improved abdominal bloating vs. placebo (P<0.05 for all secondary
      endpoints, controlling for multiplicity). Approximately one-third of linaclotide
      patients (each group) had >=50% mean decrease from baseline in abdominal bloating
      vs. 18% of placebo patients (P<0.01). Diarrhea was reported in 6% and 17% of
      linaclotide 145 and 290 MUg patients, respectively, and 2% of placebo patients.
      AEs resulted in premature discontinuation of 5% and 9% of linaclotide 145 MUg and
      290 MUg patients, respectively, and 6% of placebo patients. CONCLUSIONS: Once
      daily linaclotide (145 and 290 MUg) significantly improved bowel and abdominal
      symptoms in chronic idiopathic constipation patients with moderate-to-severe
      baseline abdominal bloating; in particular, linaclotide significantly improved
      abdominal bloating compared to placebo, an important finding given the lack of
      agents available to treat abdominal bloating in chronic idiopathic constipation
      patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01642914.

PMID- 26222319
TI  - Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3
      dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and
      Highly Selective PARP-1 Inhibitor for Cancer Therapy.
AB  - The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established
      role in the signaling and repair of DNA and is a prominent target in oncology, as
      testified by the number of candidates in clinical testing that unselectively
      target both PARP-1 and its closest isoform PARP-2. The goal of our program was to
      find a PARP-1 selective inhibitor that would potentially mitigate toxicities
      arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary
      Nerviano Medical Sciences (NMS) chemical collection, followed by SAR
      optimization, allowed us to discover 2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]
      6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118
      proved to be a potent, orally available, and highly selective PARP-1 inhibitor
      endowed with excellent ADME and pharmacokinetic profiles and high efficacy in
      vivo both as a single agent and in combination with Temozolomide in MDA-MB-436
      and Capan-1 xenograft models, respectively. Cocrystal structures of 20by with
      both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the
      observed selectivity. 

PMID- 26222320
TI  - Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat
      model of traumatic brain injury.
AB  - Traumatic brain injury (TBI) is one of the main causes of intellectual and
      cognitive disabilities. In the clinic it is essential to limit the development of
      cognitive impairment after TBI. In this study, the effects of gallic acid (GA;
      100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on
      neurological score, passive avoidance memory, long-term potentiation (LTP)
      deficits, and levels of proinflammatory cytokines including interleukin-1 beta
      (IL-1beta), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in
      the brain have been evaluated. Brain injury was induced following Marmarou's
      method. Data were analyzed by one-way and repeated measures ANOVA followed by
      Tukey's post-hoc test. The results indicated that memory was significantly
      impaired (p < 0.001) in the group treated with TBI + vehicle, together with
      deterioration of the hippocampal LTP and increased brain tissue levels of IL
      1beta, IL-6, and TNF-alpha. GA treatment significantly improved memory and LTP in
      the TBI rats. The brain tissue levels of IL-1beta, IL-6, and TNF-alpha were
      significantly reduced (p < 0.001) in the group treated with GA. The results
      suggest that GA has neuroprotective properties against TBI-induced behavioral,
      electrophysiological, and inflammatory disorders, probably via the decrease of
      cerebral proinflammatory cytokines.

PMID- 26222321
TI  - The Evolution of an Elective in Health Disparities and Advocacy: Description of
      Instructional Strategies and Program Evaluation.
AB  - PROBLEM: Health disparities remain pervasive in the United States. Training
      future physicians to address health disparities requires attention to both
      systemic and provider causes of disparities, but comprehensive curricula are
      lacking. APPROACH: Albert Einstein College of Medicine in Bronx, New York, offers
      a 13-session health disparities elective to first-year medical students. The
      curriculum covers three main content areas: background, provider contributions to
      health disparities, and systemic contributions to health disparities (i.e.,
      social determinants of health). Teaching methods included didactic and multimedia
      presentations, reflective discussions, and skill-building seminars (e.g.,
      addressing subconscious assumptions and advocacy training).The authors evaluated
      the course in 2010-2013 by comparing students' summary scores for knowledge,
      attitudes, and self-reported confidence on pre- and postintervention tests. They
      investigated associations between students' sociodemographic characteristics and
      changes in summary scores. OUTCOMES: Scores increased significantly in each
      domain: Mean knowledge scores increased from 63.6 (+/- 10.0), out of 100, to 76.4
      (+/- 12.8); mean attitudes scores increased from 16.7 (+/- 1.9), out of 20, to
      18.2 (+/- 1.1); mean confidence scores increased from 10.7 (+/- 1.5), out of 16,
      to 14.4 (+/- 1.7). Younger students (< 24) had greater changes in confidence than
      older students. Other sociodemographic characteristics were not associated with
      changes in any domain. NEXT STEPS: Exposure to health disparities instruction is
      important for medical students. The authors' experience provides insights for
      incorporating such material into the compulsory curriculum. Future evaluation of
      outcomes from similar curricula should include measures of clinical behaviors
      (e.g., through clinical examinations).

PMID- 26222322
TI  - Creating and Maintaining a Successful Service Line in an Academic Medical Center
      at the Dawn of Value-Based Care: Lessons Learned From the Heart and Vascular
      Service Line at UMass Memorial Health Care.
AB  - The service line (SL) model has been proven to help shift health care toward
      value-based services, which is characterized by coordinated, multidisciplinary,
      high-quality, and cost-effective care. However, academic medical centers struggle
      with how to effectively set up SL structures that overcome the organizational and
      cultural challenges associated with simultaneously delivering the highest-value
      care for the patient and advancing the academic mission. In this article, the
      authors examine the evolution of UMass Memorial Health Care's heart and vascular
      service line (HVSL) from 2006 to 2011 and describe the impact on its success of
      multiple strategic decisions. These include key academic physician leadership
      recruitments and engagement via a matrixed governance and management model;
      development of multidisciplinary teams; empowerment of SL leadership through
      direct accountability and authority over programs and budgets; joint educational
      and training programs; incentives for academic achievement; and co-localization
      of faculty, personnel, and facilities. The authors also explore the barriers to
      success, including the need to overcome historical departmental-based silos,
      cultural and training differences among disciplines, confusion engendered by a
      matrixed reporting structure, and faculty's unfamiliarity with the financial and
      organizational skills required to operate a successful SL. Also described here is
      the impact that successful implementation of the SL has on creating high-quality
      services, increased profitability, and contribution to the financial stability
      and academic achievement of the academic medical center. 

PMID- 26222323
TI  - Do Faculty Benefit From Participating in a Standardized Patient Assessment as
      Part of Rater Training? A Qualitative Study.
AB  - PURPOSE: To explore faculty's experience participating in a standardized patient
      (SP) assessment where they were observed and assessed and then received feedback
      about their own clinical skills as part of a rater training faculty development
      program on direct observation. METHOD: In 2012, 45 general internist teaching
      faculty from 30 residency programs participated in an eight-station SP assessment
      with cases covering common clinical scenarios. Twenty-one participants (47%)
      received verbal feedback from SPs and a performance-based score report. All
      participants reflected on the experience through an independent written exercise,
      one-on-one interviews, and a focus group discussion. Grounded theory was used to
      analyze all three reflections. RESULTS: Eleven participants (24%) previously
      completed an SP assessment post training. Most found the SP assessment valuable
      and experienced emotions that increased their empathy for learners' experiences
      being observed, being assessed, and receiving nonspecific feedback. Participants
      receiving verbal feedback from SPs described different themes around personal
      improvement plans compared with the nonfeedback group. CONCLUSIONS: Faculty
      experience many of the same emotions as trainees during SP encounters and view SP
      assessment as a valuable mechanism to improve their own clinical skills and
      assessments of trainees. SP assessments may be one approach to provide faculty
      feedback about core clinical skills needed in their own patient care as well as
      what they are expected to teach trainees. Although actual changes in
      participants' clinical or assessor skills were not measured (more research is
      merited), findings hint at a "dual benefit" from incorporating SP assessment into
      a faculty development workshop about assessment.

PMID- 26222324
TI  - Supporting Medical Students' Pursuit of Longitudinal Patient Experiences:
      Piloting an Innovative Visit Notification Tool at the Massachusetts General
      Hospital.
AB  - PROBLEM: Both medical educators and students have an increasing interest in
      longitudinal patient experiences (LPE) that allow students to work with patients
      at multiple points in time, often across multiple clinical settings. Despite this
      interest in LPE, following patients over time and across health systems remains a
      challenge. APPROACH: In August 2012-May 2013, with faculty support, two third
      year medical students implemented a pilot program at the Massachusetts General
      Hospital (MGH) in the third-year block clerkship curriculum. One of the authors
      modified an existing novel, electronic visit notification tool (VNT) that
      integrates with the electronic medical record (EMR) to help students follow
      patients longitudinally. Students added patients to their cohort after obtaining
      the patient's verbal consent. Each week, the VNT sent students e-mails notifying
      them of all scheduled appointments for their cohort patients at all Partners
      HealthCare-affiliated sites. OUTCOMES: Each pilot student added approximately 20
      patients to her cohort and followed 3-5 patients consistently. The pilot students
      felt the VNT made it significantly easier to follow patients over time, their
      appreciation of chronic illness care developed, and they gained a greater
      understanding of the integrated nature of patient care. NEXT STEPS: On the basis
      of student interest, the tool was made available to all MGH third-year students
      in March-May 2013 and offered to all MGH third-year students at the beginning of
      the next clinical year. Notification tools such as the VNT may enhance a
      hospital's existing EMR and facilitate longitudinal educational goals across all
      clinical clerkship models.

PMID- 26222325
TI  - Association Between Hyponatremia and Complicated Appendicitis.

PMID- 26222326
TI  - Visual Hallucinations with Methylphenidate and Acetaminophen in Combination.

PMID- 26222327
TI  - Revealing the Nature of Interaction between Graphene Oxide and Lipid Membrane by
      Surface-Enhanced Infrared Absorption Spectroscopy.
AB  - Revealing the nature of interaction between graphene oxide (GO) and lipid
      membrane is a crucial issue but still remains challenging. Here, we describe our
      recent effort toward this direction by studying the GO-induced vibrational
      changes of interfacial water and lipid membrane with surface-enhanced infrared
      absorption (SEIRA) spectroscopy. The experimental results provide evidence that
      overcoming the electrostatic repulsion of phosphate group, its hydrogen bonding
      attraction as well as the electrostatic and hydrophobic interaction of choline
      group are the driving forces for the effective adsorption of GO on lipid
      membrane. This work will open exciting new avenues to explore the use of SEIRA
      spectroscopy technique in probing nanobio interface. 

PMID- 26222328
TI  - Neuro-mechanical adjustments to shod versus barefoot treadmill runs in the acute
      and delayed stretch-shortening cycle recovery phases.
AB  - In habitually shod recreational runners, we studied the combined influence of
      footwear and stretch-shortening cycle (SSC) fatigue on treadmill running pattern,
      paying special attention to neuro-mechanical adjustments in the acute and 2-day
      delayed recovery periods. The SSC exercise consisted of a series of 25 sub
      maximal rebounds on a sledge apparatus repeated until exhaustion. The acute and
      delayed functional fatigue effects were quantified in a maximal drop jump test.
      The neuro-mechanical adjustments to fatigue were examined during two submaximal
      treadmill run tests of 3 min performed either barefoot or with shoes on. Surface
      electromyographic (EMG) activities, tibial accelerations and kinematics of the
      right lower limb were recorded during the first and last 15 s of each run. The
      main result was that neuro-mechanical differences between the shod and barefoot
      running patterns, classically reported in the absence of fatigue, persisted in
      the fatigued state. However, in the delayed recovery phase, rearfoot eversion was
      found to significantly increase in the shod condition. This specific footwear
      effect is considered as a potential risk factor of overuse injuries in longer
      runs. Therefore, specific care should be addressed in the delayed recovery phase
      of SSC fatigue and the use of motion control shoes could be of interest. 

PMID- 26222329
TI  - Pharmacokinetics of meropenem in children receiving continuous renal replacement
      therapy: Validation of clinical trial simulations.
AB  - Meropenem is frequently prescribed in critically ill children receiving
      continuous renal replacement therapy (CRRT). We previously used clinical trial
      simulations to evaluate dosing regimens of meropenem in this population and
      reported that a dose of 20 mg/kg every 12 hours optimizes target attainment.
      Meropenem pharmacokinetics were investigated in this prospective, open-label
      study to validate our previous in silico predictions. Seven patients received
      meropenem (13.8-22 mg/kg) administered intravenously every 12 hours as part of
      standard care. A mean dose of 18.6 mg/kg of meropenem was administered, resulting
      in a mean peak concentration of 80.1 MUg/mL. Meropenem volume of distribution was
      0.35 +/- 0.085 L/kg. CRRT clearance was 40.2 +/- 6.6 mL/(min . 1.73 m(2) ) and
      accounted for 63.4% of the total clearance of 74.8 +/- 36.9 mL/(min . 1.73 m(2)
      ). Simulations demonstrated that a dose of 20 mg/kg every 12 hours resulted in a
      time above the minimum inhibitory concentration (%fT > MIC) of 100% in 5 out of 7
      subjects, with a %fT > MIC of 93% and 43% in the remaining 2 subjects. We
      conclude that CRRT contributed significantly to the total clearance of meropenem.
      A dosing regimen of 20 mg/kg achieved good target attainment in critically ill
      children receiving CRRT, which is consistent with our previously published in
      silico predictions. 

PMID- 26222330
TI  - Correction: Calcium specificity signaling mechanisms in abscisic acid signal
      transduction in Arabidopsis guard cells.

PMID- 26222331
TI  - Climate change alters plant biogeography in Mediterranean prairies along the West
      Coast, USA.
AB  - Projected changes in climate are expected to have widespread effects on plant
      community composition and diversity in coming decades. However, multisite,
      multifactor climate manipulation studies that have examined whether observed
      responses are regionally consistent and whether multiple climate perturbations
      are interdependent are rare. Using such an experiment, we quantified how warming
      and increased precipitation intensity affect the relative dominance of plant
      functional groups and diversity across a broad climate gradient of Mediterranean
      prairies. We implemented a fully factorial climate manipulation of warming (+2.5
      3.0  degrees C) and increased wet-season precipitation (+20%) at three sites
      across a 520-km latitudinal gradient in the Pacific Northwest, USA. After seeding
      with a nearly identical mix of native species at all sites, we measured plant
      community composition (i.e., cover, richness, and diversity), temperature, and
      soil moisture for 3 years. Warming and the resultant drying of soils altered
      plant community composition, decreased native diversity, and increased total
      cover, with warmed northern communities becoming more similar to communities
      further south. In particular, after two full years of warming, annual cover
      increased and forb cover decreased at all sites mirroring the natural
      biogeographic pattern. This suggests that the extant climate gradient of
      increasing heat and drought severity is responsible for a large part of the
      observed biogeographic pattern of increasing annual invasion in US West Coast
      prairies as one moves further south. Additional precipitation during the rainy
      season did little to relieve drought stress and had minimal effects on plant
      community composition. Our results suggest that the projected increase in drought
      severity (i.e., hotter, drier summers) in Pacific Northwest prairies may lead to
      increased invasion by annuals and a loss of forbs, similar to what has been
      observed in central and southern California, resulting in novel species
      assemblages and shifts in functional composition, which in turn may alter
      ecosystem functions.

PMID- 26222332
TI  - Molecular Dynamics Simulation Study of the Early Stages of Nucleation of Iron
      Oxyhydroxide Nanoparticles in Aqueous Solutions.
AB  - Nucleation is a fundamental step in crystal growth. Of environmental and
      materials relevance are reactions that lead to nucleation of iron oxyhydroxides
      in aqueous solutions. These reactions are difficult to study experimentally due
      to their rapid kinetics. Here, we used classical molecular dynamics simulations
      to investigate nucleation of iron hydroxide/oxyhydroxide nanoparticles in aqueous
      solutions. Results show that in a solution containing ferric ions and hydroxyl
      groups, iron-hydroxyl molecular clusters form by merging ferric monomers, dimers,
      and other oligomers, driven by strong affinity of ferric ions to hydroxyls. When
      deprotonation reactions are not considered in the simulations, these clusters
      aggregate to form small iron hydroxide nanocrystals with a six-membered ring-like
      layered structure allomeric to gibbsite. By comparison, in a solution containing
      iron chloride and sodium hydroxide, the presence of chlorine drives cluster
      assembly along a different direction to form long molecular chains (rather than
      rings) composed of Fe-O octahedra linked by edge sharing. Further, in chlorine
      free solutions, when deprotonation reactions are considered, the simulations
      predict ultimate formation of amorphous iron oxyhydroxide nanoparticles with
      local atomic structure similar to that of ferrihydrite nanoparticles. Overall,
      our simulation results reveal that nucleation of iron oxyhydroxide nanoparticles
      proceeds via a cluster aggregation-based nonclassical pathway. 

PMID- 26222333
TI  - Sublethal effects of multiwalled carbon nanotube exposure in the invertebrate
      Daphnia magna.
AB  - Carbon nanotubes were previously demonstrated to accumulate on the carapace and
      in the gut of daphnids in aquatic exposures. The purpose of the present study was
      to assess the effects of multiwalled carbon nanotube (MWCNT) exposure on the
      sublethal Daphnia magna endpoints swimming behavior, algal feeding, growth, and
      reproduction and to determine the relative magnitude of difference between lethal
      and sublethal toxicity thresholds in 48-h and 14-d exposures. A stable dispersion
      of MWCNTs was prepared using 100 mg/L natural organic matter (NOM), and all
      treatments were compared statistically to a NOM control. The swimming behavior
      endpoints of mean velocity and total distance moved were determined using digital
      tracking software. For the acute (48-h) exposure, a 50% lethal concentration
      (LC50) of 29.3 (23.6-36.3) mg/L and a 50% effective concentration (EC50) of 6.7
      mg/L in the swimming velocity endpoint were determined. When swimming response
      was nonmonotonic below 2 mg/L, consistent reductions in velocity were observed at
      6.9 mg/L and above. Median effect concentrations were lower in the chronic (14-d)
      bioassay. The 14-d LC50 was 4.3 mg/L (3.3-5.6 mg/L), and the reproduction EC50
      was 5.0 mg/L. Lowest-observed-effect concentrations for survival and reproduction
      were 5.4 mg/L and 1.7 mg/L, respectively. Significantly fewer (23.1%) algal cells
      were consumed in the 3.9-mg/L treatment relative to the control. No significant
      effects on swimming behavior were observed for the 14-d bioassay. Less
      traditional sublethal endpoints such as swimming behavior and feeding rate may be
      especially important to assess for MWCNTs and other materials expected to be more
      physically than chemically toxic through mechanisms such as gut clogging.

PMID- 26222334
TI  - Peptide-like Polymers Exerting Effective Glioma-Targeted siRNA Delivery and
      Release for Therapeutic Application.
AB  - Lipopolymer 49, a solid-phase synthesized T-shaped peptide-like oligoamide
      containing two central oleic acids, 20 aminoethane, and two terminal cysteine
      units, is identified as very potent and biocompatible small interfering RNA
      (siRNA) carrier for gene silencing in glioma cells. This carrier is combined with
      a novel targeting polymer 727, containing a precise sequence of Angiopep 2
      targeting peptide, linked with 28 monomer units of ethylene glycol, 40
      aminoethane, and two terminal cysteines in siRNA complex formation. Angiopep
      polyethylene glycol (PEG)/siRNA polyplexes exhibit good nanoparticle features,
      effective glioma-targeting siRNA delivery, and intracellular siRNA release,
      resulting in an outstanding gene downregulation both in glioma cells and upon
      intravenous delivery in glioma model nude mice without significant biotoxicity.
      Therefore, this novel siRNA delivery system is expected to be a promising
      strategy for targeted and safe glioma therapy. 

PMID- 26222335
TI  - Diffusion tensor imaging and myelin composition analysis reveal abnormal
      myelination in corpus callosum of canine mucopolysaccharidosis I.
AB  - Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter
      foci on T2-weighted brain magnetic resonance (MR) imaging that are associated
      clinically with cognitive impairment. We report here a diffusion tensor imaging
      (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found
      that two DTI parameters, fractional anisotropy (a measure of white matter
      integrity) and radial diffusivity (which reflects degree of myelination) were
      abnormal in the corpus callosum of MPS I dogs compared to carrier controls.
      Tissue studies of the corpus callosum showed reduced expression of myelin-related
      genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs
      with recombinant alpha-L-iduronidase, which is the enzyme that is deficient in
      MPS I disease. The recombinant alpha-L-iduronidase was administered by
      intrathecal injection into the cisterna magna. Treated dogs showed partial
      correction of corpus callosum myelination. Our findings suggest that abnormal
      myelination occurs in the canine MPS I brain, that it may underlie clinically
      relevant brain imaging findings in human MPS I patients, and that it may respond
      to treatment.

PMID- 26222336
TI  - TDP-43 activates microglia through NF-kappaB and NLRP3 inflammasome.
AB  - Transactive response DNA-binding protein-43 (TDP-43) is a multifunctional nucleic
      acid binding protein present in ubiquitinated inclusions in tissues of patients
      with amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration
      (FTLD). The ALS-associated mutations in the glycine-rich C-terminal domain of TDP
      43 established a causal link between TDP-43 and disease, and conferred both loss-
      and gain-of-function properties in neurons. Since it has not been established
      whether these intra-neuronal changes are sufficient to cause ALS or whether non
      cell autonomous neuronal-glial signaling could be involved, we investigated the
      extracellular effects of TDP-43 proteins on microglial activation and motoneuron
      toxicity. Wild-type, truncated 25kD C-terminal fragments, or mutant forms of TDP
      43 all activated microglia and upregulated NOX2, TNF-alpha, and IL-1beta, with WT
      forms being significantly less effective in activating microglia. This response
      to TDP-43 was mediated by its interaction with the microglial surface CD14
      receptor and subsequent stimulation of the NF-kappaB and AP-1 pathways, as well
      as the intracellular inflammasome. At the cell surface, CD14 blocking antibodies
      suppressed microglial NF-kappaB activation and proinflammatory cytokine
      production mediated by TDP-43. Intracellularly, the NLRP3 inflammasome was
      induced and functional caspase-1 was produced augmenting the release of mature IL
      1beta. Further, TDP-43-mediated activation of microglia caused a proinflammatory
      cascade that was toxic to motoneurons. In the absence of microglia, TDP-43 was
      not toxic to motoneurons. The ability of TDP-43 to promote CD14-mediated
      activation of microglial NF-kappaB and AP-1 pathways, as well as the NLRP3
      inflammasome, suggests the involvement of a non-cell autonomous proinflammatory
      signaling that enhances motoneuron injury, and may offer novel therapeutic
      targets in ALS. 

PMID- 26222338
TI  - Large-Scale Precise Printing of Ultrathin Sol-Gel Oxide Dielectrics for Directly
      Patterned Solution-Processed Metal Oxide Transistor Arrays.
AB  - Ultrathin and dense metal oxide gate di-electric layers are reported by a simple
      printing of AlOx and HfOx sol-gel precursors. Large-area printed indium gallium
      zinc oxide (IGZO) thin-film transistor arrays, which exhibit mobilities >5 cm(2)
      V(-1) s(-1) and gate leakage current of 10(-9) A cm(-2) at a very low operation
      voltage of 2 V, are demonstrated by continuous simple bar-coated processes. 

PMID- 26222337
TI  - Deficiency of NOX1 or NOX4 Prevents Liver Inflammation and Fibrosis in Mice
      through Inhibition of Hepatic Stellate Cell Activation.
AB  - Reactive oxygen species (ROS) produced by nicotinamide adenine dinucleotide
      phosphate oxidase (NOX) play a key role in liver injury and fibrosis. Previous
      studies demonstrated that GKT137831, a dual NOX1/4 inhibitor, attenuated liver
      fibrosis in mice as well as pro-fibrotic genes in hepatic stellate cells (HSCs)
      as well as hepatocyte apoptosis. The effect of NOX1 and NOX4 deficiency in liver
      fibrosis is unclear, and has never been directly compared. HSCs are the primary
      myofibroblasts in the pathogenesis of liver fibrosis. Therefore, we aimed to
      determine the role of NOX1 and NOX4 in liver fibrosis, and investigated whether
      NOX1 and NOX4 signaling mediates liver fibrosis by regulating HSC activation.
      Mice were treated with carbon tetrachloride (CCl4) to induce liver fibrosis.
      Deficiency of either NOX1 or NOX4 attenuates liver injury, inflammation, and
      fibrosis after CCl4 compared to wild-type mice. NOX1 or NOX4 deficiency reduced
      lipid peroxidation and ROS production in mice with liver fibrosis. NOX1 and NOX4
      deficiency are approximately equally effective in preventing liver injury in the
      mice. The NOX1/4 dual inhibitor GKT137831 suppressed ROS production as well as
      inflammatory and proliferative genes induced by lipopolysaccharide (LPS),
      platelet-derived growth factor (PDGF), or sonic hedgehog (Shh) in primary mouse
      HSCs. Furthermore, the mRNAs of proliferative and pro-fibrotic genes were
      downregulated in NOX1 and NOX4 knock-out activated HSCs (cultured on plastic for
      5 days). Finally, NOX1 and NOX4 protein levels were increased in human livers
      with cirrhosis compared with normal controls. Thus, NOX1 and NOX4 signaling
      mediates the pathogenesis of liver fibrosis, including the direct activation of
      HSC. 

PMID- 26222339
TI  - Visceral Adipose Tissue in Patients with Crohn's Disease Correlates with Disease
      Activity, Inflammatory Markers, and Outcome.
AB  - BACKGROUND: Visceral adipose tissue (VAT) could affect Crohn's disease (CD);
      however, no prospective clinical studies have explored the issue. METHODS: We
      measured VAT with magnetic resonance imaging and total fat mass (FM) with air
      displacement plethysmography in 31 women with CD in remission and 19 matched
      control women. We assessed the VAT/FM ratio as index of VAT accumulation,
      measured cytokines, and monitored clinical features (duration of remission,
      disease behavior, and outcome) in patients with CD retrospectively and
      prospectively. We also tested whether ultrasound could provide a surrogate marker
      of VAT in patients with CD. RESULTS: Patients with CD had higher percentage of FM
      (37 +/- 10% versus 31 +/- 10%, P = 0.03), VAT (1885 +/- 1403 mL versus 941 +/-
      988 mL, P = 0.02), and VAT/FM ratio (65 +/- 24 mL/kg versus 37 +/- 25 mL/kg, P =
      0.004) than control women. In patients with CD, VAT/FM ratio was associated with
      leptin (P = 0.009) and interleukin 6 (P = 0.032) concentrations, and higher in
      short-term than in long-term remission (72.6 +/- 27.1 mL/kg versus 54.8 +/- 16.1
      mL/kg, P = 0.079). Patients with CD with stricturing/fistulizing disease had a
      higher VAT/FM ratio than patients with nonstricturing/nonfistulizing behavior (79
      +/- 0.15 mL/kg versus 63 +/- 28 mL/kg, P = 0.067). A higher baseline VAT/FM ratio
      was associated with an increased disease activity at follow-up (P = 0.029). The
      ultrasound-determined thickness between the abdominal wall and the aorta was
      strongly associated with VAT as measured by magnetic resonance imaging (P <
      0.001). CONCLUSIONS: VAT accumulation could be a prospective risk factor for
      increased disease activity in CD.

PMID- 26222340
TI  - Different Profile of Efficacy of Thiopurines in Ulcerative Colitis and Crohn's
      Disease.
AB  - BACKGROUND: Thiopurines are effective drugs in treating ulcerative colitis (UC)
      and Crohn's disease (CD) even if studies that specifically investigate these
      drugs' profile of efficacy in UC compared with CD are scarce. Our aim was to
      compare the profile of efficacy of thiopurines in patients with UC and CD.
      METHODS: We perfomed a longitudinal observational study evaluating steroid-free
      clinical remission (CR) and mucosal healing (MH) in all patients with UC and CD
      who would complete 2 years of maintenance treatment with thiopurines. In patients
      with UC, CR and MH were assessed before starting treatment and 2 years later
      using the Mayo score (CR = Mayo score <2; MH = Mayo subscore <=1). In patients
      with CD, CR and MH were assessed at the same time points using the Crohn's
      disease activity index (CR = Crohn's disease activity index < 150) and the
      Simplified Endoscopic Score for Crohn's Disease (MH = Simplified Endoscopic Score
      for Crohn's Disease < 2). The efficacy of thiopurines was assessed through
      intention-to-treat and per-protocol analyses. RESULTS: The study included 205
      steroid-dependent patients (104 UC; 101 CD), 140 of whom (70 UC; 70 CD) completed
      the 2-year observation period. Steroid-free CR was recorded in 43 patients with
      UC and 37 with CD (intention-to-treat: 41% versus 36%; P = 0.6; per-protocol: 61%
      versus 53%; P = 0.4); MH was obtained in 38 patients with UC and 17 with CD
      (intention-to-treat: 36% versus 16%; P < 0.01; odds ratio, 2.9; per-protocol: 54%
      versus 25%; P < 0.01; odds ratio, 3.7). CONCLUSIONS: Thiopurines are effective in
      maintaining steroid-free CR in both UC and CD although they show a better profile
      of efficacy in terms of MH in cases of UC.

PMID- 26222341
TI  - Intestinal Inflammation Leads to a Long-lasting Increase in Resistance to
      Systemic Salmonellosis that Requires Macrophages But Not B or T Lymphocytes at
      the Time of Pathogen Challenge.
AB  - BACKGROUND: Intestinal inflammation is associated with systemic translocation of
      commensal antigens and the consequent activation of B and T lymphocytes. The long
      term consequences of such immune activation are not completely understood.
      METHODS: C57BL/6 mice were subjected to 2 courses of treatment with dextran
      sulfate sodium (DSS) to induce colitis. Two to 7 weeks after the DSS treatment,
      the mice were infected intraperitoneally with Salmonella enterica serovar
      Typhimurium. The outcome of infection was evaluated based on survival and tissue
      pathogen burden. RESULTS: Mice that had recovered from DSS colitis displayed a
      significant increase in resistance to S. Typhimurium infection as indicated by
      improved survival and decreased tissue pathogen numbers. The colitis-induced
      increase in resistance to systemic salmonellosis lasted for as long as 7 weeks
      after discontinuing DSS and was dependent on T lymphocytes but not on B cells.
      Interestingly, depletion of CD4 and CD8 T cells just before the Salmonella
      infection did not alter the colitis-induced increase in resistance. Mice that had
      recovered from colitis had evidence of persistent activation of resident
      peritoneal macrophages and enhanced Salmonella-induced neutrophil recruitment to
      the peritoneum. Macrophage depletion with clodronate liposomes abrogated the
      colitis-induced increase in resistance to Salmonella. CONCLUSIONS: Taken
      together, our results indicate that DSS colitis leads to a long-lasting increase
      in resistance to Salmonella infection that is initiated in a T cell-dependent
      manner but is ultimately mediated independently of B and T cells as a result of
      persistent changes in innate immune cell function.

PMID- 26222342
TI  - Blood and Urinary Abnormalities Induced During and After 24-Hour Continuous
      Running: A Case Report.
AB  - In this reported clinical case, a healthy and well-trained male subject [aged 37
      years, maximal oxygen uptake (V[Combining Dot Above]O2max) 64 mL.kg.min] ran for
      23 hours and 35 minutes covering 160 km (6.7 km/h average running speed). The
      analysis of hematological and biochemical parameters 3 days before the event,
      just after termination of exercise, and after 24 and 48 hours of recovery
      revealed important changes on muscle and liver function, and hemolysis. The
      analysis of urine sediments showed an increment of red and white blood cells
      filtrations, compatible with transient nephritis. After 48 hours, most of these
      alterations were recovered. Physicians and health professionals who monitor such
      athletic events should be aware that these athletes could exhibit transient
      symptoms compatible with severe pathologies and diseases, although the genesis of
      these blood and urinary abnormalities are attributable to transient physiological
      adaptations rather to pathological status. 

PMID- 26222343
TI  - A protocol for a systematic review of effective home support to people with
      dementia and their carers: components and impacts.
AB  - AIM: To review the evidence for home support approaches directed at tertiary
      prevention; ameliorating difficulties and enhancing well-being. BACKGROUND: With
      population ageing dementia represents a significant care challenge with 60% of
      people with dementia living at home. However, little is known about existing
      forms of home support and their relative effectiveness. DESIGN: A two-stage
      design: First, an overview of systematic reviews of psychosocial interventions
      for dementia to identify their components; second, a systematic review of the
      effectiveness of home support interventions to older people with dementia/their
      carers. METHODS: We will search electronic databases using specific search terms
      with additional searches of other known studies. Data will be extracted by two
      reviewers according to pre-determined categories. An initial synthesis will
      elicit components of interventions from stage 1 and operationalize them in terms
      of specific techniques. These will then be used in synthesis of data in stage 2,
      to determine the extent to which each home support intervention relies on these
      components and distill evidence concerning outcomes. Studies from stage 2 are
      expected to be methodologically diverse; if so, a narrative approach to synthesis
      will be taken. Study findings will be explored with Patient, Public and Carer
      Involvement groups. DISCUSSION: The review seeks to develop a theory of home
      support: how and why interventions may work; in what contexts; and for whom. We
      will identify effective home support approaches, informing policy-makers and
      establishing how they might be experienced by people with dementia and their
      carers.

PMID- 26222344
TI  - Ecological prospective memory assessment in children with acquired brain injury
      using the Children's Cooking Task.
AB  - Prospective memory (PM) has been shown to be impaired in children with acquired
      brain injuries (ABI) and is a major concern for parents. Few studies have
      addressed this issue and most used tasks that are not ecologically valid. The
      aims of this study were (1) to explore if children who have sustained an ABI
      suffer PM impairment, measured both by the Children's Cooking task (CCT) PM score
      and using the 2 PM subtests of the Rivermead Behavioral Memory Test (RBMT), and
      (2) to explore if the CCT PM score is sensitive to developmental changes in PM in
      typically developing children and in children with ABI. Fifty-four children with
      ABI and 33 typically developing controls participated in the study. Children with
      ABI had significantly lower PM scores and poorer performance in the CCT than
      their typically developing peers. PM scores increased significantly with age,
      indicating developmental progress of PM performance.

PMID- 26222345
TI  - Does Spinal Block Through Tattooed Skin Cause Histological Changes in Nervous
      Tissue and Meninges?: An Experimental Model in Rabbits.
AB  - BACKGROUND AND OBJECTIVES: Although there is no documented evidence that tattoo
      pigments can cause neurological complications, the implications of performing
      neuraxial anesthesia through tattooed skin are unknown. In this study, we aimed
      to assess whether spinal puncture performed through tattooed skin of rabbits
      determines changes over the spinal cord and meninges. In addition, we sought to
      evaluate the presence of ink fragments entrapped in spinal needles. METHODS:
      Thirty-six young male adult rabbits, each weighing between 3400 and 3900 g and
      having a spine length between 38.5 and 39 cm, were divided by lot into 3 groups
      as follows: GI, spinal puncture through tattooed skin; GII, spinal puncture
      through tattooed skin and saline injection; and GIII, spinal puncture through
      skin free of tattoo and saline injection. After intravenous anesthesia with
      ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under
      ultrasound guidance with a 22-gauge 21/2 Quincke needle. Animals in GII and GIII
      received 5 MUL/cm of spinal length (0.2 mL) of saline intrathecally. In GI, the
      needle tip was placed into the yellow ligament, and no solution was injected into
      the intrathecal space; after tattooed skin puncture, 1 mL of saline was injected
      through the needle over a histological slide to prepare a smear that was dyed by
      the Giemsa method to enable tissue identification if present. All animals
      remained in captivity for 21 days under medical observation and were killed by
      decapitation. The lumbosacral spinal cord portion was removed for histological
      analysis using hematoxylin-eosin stain. RESULTS: None of the animals had impaired
      motor function or decreased nociception during the period of clinical
      observation. None of the animals from the control group (GIII) showed signs of
      injuries to meninges. In GII, however, 4 animals presented with signs of
      meningeal injury. The main histological changes observed were focal areas of
      perivascular lymphoplasmacyte infiltration in the pia mater and arachnoid. There
      was no signal of injury in neural tissue in any animal of both groups. Tissue
      coring containing ink pigments was noted in all GI smears from the spinal needles
      used to puncture the tattooed skin. CONCLUSIONS: On the basis of the present
      results, intrathecal injection of saline through a needle inserted through
      tattooed skin is capable of producing histological changes over the meninges of
      rabbits. Ink fragments were entrapped inside the spinal needles, despite the
      presence of a stylet.

PMID- 26222346
TI  - The Ultrasound-Guided Retroclavicular Block: A Prospective Feasibility Study.
AB  - BACKGROUND AND OBJECTIVES: The aim of this feasibility study was to determine the
      success rate (sensory and surgical) of the novel retroclavicular block and to
      thoroughly describe the technique. In addition, needle tip and shaft visibility,
      needling time, procedural discomfort, motor block success rate, patient
      satisfaction at 48-hour follow-up, and complications were also recorded. METHODS:
      Fifty patients scheduled for distal upper limb surgery received an in-plane,
      single-shot, ultrasound-guided retroclavicular block with 40 mL of mepivacaine
      1.5% with epinephrine 2.5 MUg/mL. Block success was defined as a sensory score of
      10/10 for the 5 nerves supplying the distal upper limb at 30 minutes. Surgical
      success, needle visibility, needling time, axillary artery depth, motor block
      rate, patient discomfort with technique, satisfaction at 48 hours, and
      complications were also recorded. All blocks were video-recorded and timed for
      further independent assessment. A chest x-ray was obtained before discharge.
      RESULTS: Forty-five patients had a total sensory score of 10/10 at 30 minutes
      (90% success rate). Surgical success rate was 96%. Mean needling time was 3.77
      minutes (25th-75th percentiles, 2.90-6.53 minutes) with a mean axillary artery
      depth of 3.1 +/- 0.7 cm. Procedure-related discomfort (mean visual analog scale,
      1.9 +/- 1.2) was low. Mean 48-hour patient satisfaction rate (9.2 +/- 1.1), mean
      needle tip (Likert scale, 3.0 +/- 0.9), and shaft visibility (3.9 +/- 0.9) were
      high. One vascular puncture and two transient paresthesias were recorded. No
      pneumothorax was revealed by chest x-ray. CONCLUSIONS: In this study, the novel
      retroclavicular block offered a quick, safe, and reliable alternative for distal
      arm block. Further studies, comparing this approach with the classic
      infraclavicular block, are required to validate its efficacy, safety, and
      reliability.

PMID- 26222347
TI  - Chronological Changes in Ropivacaine Concentration and Analgesic Effects Between
      Transversus Abdominis Plane Block and Rectus Sheath Block.
AB  - BACKGROUND AND OBJECTIVES: Transversus abdominis plane block (TAPB) and rectus
      sheath block (RSB) are popular methods of controlling postoperative pain.
      Chronological changes in blood concentrations of local anesthetics have not been
      described, although a large amount of local anesthetic is required to block these
      compartments. We postulated that blood concentrations of anesthetics would peak
      earlier during TAPB than RSB (primary end point). Secondary end points were
      elapsed time from block until first postoperative rescue analgesia and affected
      dermatomes. METHODS: This prospective, randomized study included 22 patients
      scheduled for laparoscopic ovarian surgery under general anesthesia. The patients
      were randomized to receive either a bilateral single-shot TAPB or a bilateral RSB
      (15 mL of 0.5% ropivacaine per side). Arterial blood was sampled 10, 20, 30, 45,
      60, 90, and 120 minutes after ropivacaine administration. This trial was
      registered at the UMIN-Clinical Trials Registry (UMIN000012133) before patient
      recruitment. RESULTS: Arterial ropivacaine levels after block peaked earlier in
      the TAPB than in RSB [Tmax: 35 (12) vs 53 (16) minutes; P = 0.02], whereas peak
      ropivacaine concentrations did not significantly differ between the groups [Cmax:
      1.83 (0.41) vs 1.79 (0.33) MUg/mL; P = 0.54]. Peak ropivacaine concentrations
      exceeded 2.2 MUg/mL in 1 and 2 patients in the RSB and TAPB groups, respectively,
      although symptoms of local anesthetic systemic toxicity were not evident in any
      of them. The median [interquartile range] duration of analgesia was significantly
      longer for TAPB than RSB (421 [335-536] vs 196 [168-277] minutes; P = 0.01).
      CONCLUSIONS: Peak ropivacaine concentrations were comparable during TAPB and RSB,
      but peaked earlier during TAPB. Although 150 mg of ropivacaine remained effective
      significantly longer during TAPB than RSB during laparoscopic surgery, this dose
      could cause local anesthetic systemic toxicity. The analgesic effects of blocks
      with less ropivacaine should be assessed.

PMID- 26222348
TI  - A Novel Modified Retrocrural Approach for Celiac Plexus Block: The Single-Needle
      Retroaortic Technique.
AB  - For patients with pain from upper abdominal malignancies, celiac plexus
      neurolysis can provide an effective means of pain control. However, there are
      instances when traditionally described percutaneous approaches may not be
      technically feasible. We describe here the successful use of a novel single
      needle retroaortic approach as an alternative approach to celiac plexus
      neurolysis.We present 4 cases of patients with pain from upper abdominal
      malignancies in whom we performed celiac plexus neurolysis using a novel single
      needle retroaortic approach. All 4 patients had significant pain relief and no
      significant adverse effects from the retroaortic approach. 

PMID- 26222349
TI  - Reliability of Quantitative Sensory Tests in a Low Back Pain Population.
AB  - BACKGROUND AND OBJECTIVES: Reliability is an essential condition for using
      quantitative sensory tests (QSTs) in research and clinical practice, but
      information on reliability in patients with chronic pain is sparse. The aim of
      this study was to evaluate the reliability of different QST in patients with
      chronic low back pain. METHODS: Eighty-nine patients with chronic low back pain
      participated in 2 identical experimental sessions, separated by at least 7 days.
      The following parameters were recorded: pressure pain detection and tolerance
      thresholds at the toe, electrical pain thresholds to single and repeated
      stimulation, heat pain detection and tolerance thresholds at the arm and leg,
      cold pain detection threshold at the arm and leg, and conditioned pain modulation
      using the cold pressor test. Reliability was analyzed using the coefficient of
      variation, the coefficient of repeatability, and the intraclass correlation
      coefficient. It was judged as acceptable or not based primarily on the analysis
      of the coefficient of repeatability. RESULTS: The reliability of most tests was
      acceptable. Exceptions were cold pain detection thresholds at the leg and arm.
      CONCLUSIONS: Most QST measurements have acceptable reliability in patients with
      chronic low back pain.

PMID- 26222350
TI  - The number of seizures needed in the EMU.
AB  - OBJECTIVE: The purpose of this study was to develop a quantitative framework to
      estimate the likelihood of multifocal epilepsy based on the number of unifocal
      seizures observed in the epilepsy monitoring unit (EMU). METHODS: Patient records
      from the EMU at Massachusetts General Hospital (MGH) from 2012 to 2014 were
      assessed for the presence of multifocal seizures as well the presence of
      multifocal interictal discharges and multifocal structural imaging abnormalities
      during the course of the EMU admission. Risk factors for multifocal seizures were
      assessed using sensitivity and specificity analysis. A Kaplan-Meier survival
      analysis was used to estimate the risk of multifocal epilepsy for a given number
      of consecutive seizures. To overcome the limits of the Kaplan-Meier analysis, a
      parametric survival function was fit to the EMU subjects with multifocal seizures
      and this was used to develop a Bayesian model to estimate the risk of multifocal
      seizures during an EMU admission. RESULTS: Multifocal interictal discharges were
      a significant predictor of multifocal seizures within an EMU admission with a p <
      0.01, albeit with only modest sensitivity 0.74 and specificity 0.69. Multifocal
      potentially epileptogenic lesions on MRI were not a significant predictor p =
      0.44. Kaplan-Meier analysis was limited by wide confidence intervals secondary to
      significant patient dropout and concern for informative censoring. The Bayesian
      framework provided estimates for the number of unifocal seizures needed to
      predict absence of multifocal seizures. To achieve 90% confidence for the absence
      of multifocal seizure, three seizures are needed when the pretest probability for
      multifocal epilepsy is 20%, seven seizures for a pretest probability of 50%, and
      nine seizures for a pretest probability of 80%. SIGNIFICANCE: These results
      provide a framework to assist clinicians in determining the utility of trying to
      capture a specific number of seizures in EMU evaluations of candidates for
      epilepsy surgery.

PMID- 26222351
TI  - Could side of middle cerebral artery obstruction be a prognostic factor for
      mortality in thrombolysed patients?

PMID- 26222352
TI  - Encephalitis by dengue virus and other arboviruses.

PMID- 26222353
TI  - Does the side of middle cerebral artery compromise matters in the mortality after
      thrombolysis in ischemic stroke?
AB  - The impact of the side in middle cerebral artery (MCA) ischemic stroke is not
      well established. Our aim was to analyze the differences between right (RMCA) and
      left middle cerebral artery (LMCA) stroke in patients submitted to intravenous
      thrombolysis and the influence of the affected side in the patient's mortality
      after 3 months. METHOD: Patients with MCA ischemic stroke submitted to
      intravenous thrombolysis from March 2010 to December 2011 at two Brazilian Stroke
      Centers were included. Differences between patients with RMCA and LMCA stroke
      were identified by univariate analysis. RESULTS: Forty-five patients with RMCA
      stroke and 67 with LMCA stroke were analyzed. Patients with LMCA had a higher
      incidence of atrial fibrillation (p = 0.031), although patients with RMCA more
      often had a previous ischemic stroke (p = 0.034). The mortality over 3 months was
      similar for either side (OR = 1.20 ;0.37 - 4.29, p = 0.772). CONCLUSION: The side
      of the MCA ischemic stroke did not influence the patients mortality.

PMID- 26222354
TI  - Incidence and mortality of ischemic stroke subtypes in Joinville, Brazil: a
      population-based study.
AB  - AIMS: To measure the incidence and mortality rates of ischemic stroke (IS)
      subtypes in Joinville, Brazil. METHODS: All first-ever IS patients that occurred
      in Joinville from January 2005 to December 2006 were identified. The IS subtypes
      were classified by the TOAST criteria, and the patients were followed-up for one
      year after IS onset. RESULTS: The age-adjusted incidence per 100,000 inhabitants
      was 26 (17-39) for large-artery atherosclerosis (LAA), 17 (11-27) for
      cardioembolic (CE), 29 (20-41) for small vessel occlusion (SVO), 2 (0.6-7) for
      stroke of other determined etiology (OTH) and 30 (20-43) for stroke of
      undetermined etiology (UND). The 1-year mortality rate per 100,000 inhabitants
      was 5 (2-11) for LAA, 6 (3-13) for CE, 1 (0.1-6) for SVO, 0.2 (0-0.9) for OTH and
      9 (4-17) for UND. CONCLUSION: In the population of Joinville, the incidences of
      IS subtypes were similar to those found in other populations. These findings
      highlight the importance of better detection and control of atherosclerotic risk
      factors.

PMID- 26222355
TI  - Memory deficit associated with increased brain proinflammatory cytokine levels
      and neurodegeneration in acute ischemic stroke.
AB  - The present study aimed to investigate behavioral changes and neuroinflammatory
      process following left unilateral common carotid artery occlusion (UCCAO), a
      model of cerebral ischemia. Post-ischemic behavioral changes following 15 min
      UCCAO were recorded 24 hours after reperfusion. The novel object recognition task
      was used to assess learning and memory. After behavioral test, brains from sham
      and ischemic mice were removed and processed to evaluate central nervous system
      pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA.
      UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were
      observed in the cerebrum by TTC stain. Moreover, the histopathological analysis
      revealed cerebral necrotic cavities surrounded by ischemic neurons and
      hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels
      of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham
      operated group. These findings suggest an involvement of central nervous system
      inflammatory mediators and brain damage in cognitive impairment following
      unilateral acute ischemia. 

PMID- 26222356
TI  - Combination of pharmacotherapy and lidocaine analgesic block of the peripheral
      trigeminal branches for trigeminal neuralgia: a pilot study.
AB  - Classical trigeminal neuralgia (CTN) is treated predominantly by pharmacotherapy
      but side effects and unsuccessful occurs. The current study was carried out to
      evaluate the therapeutic effect of combination of pharmacotherapy and lidocaine
      block. Thirteen patients with CTN managed with pharmacotherapy were recruited and
      assigned either to no additional treatment (Group I) or to additional analgesic
      block (Group II). The primary endpoint was the reduction in the frequency of pain
      episodes in a month assessed at 30 and 90 days. Comparisons of measurements of
      pain, general health and depression scales were secondary endpoints. The results
      from the follow-up visits at 30 and 90 days showed the Group II to have larger
      reduction in the frequency of pain and exhibited a bigger improvement in the
      scores of the pain, general health and depression scales. The results from this
      preliminary study suggest a clinical benefit of the combination of
      pharmacotherapy and lidocaine block. 

PMID- 26222357
TI  - Migraine and tension-type headache triggers in a Greek population.
AB  - Migraine and tension type headache are the two most common primary headaches. The
      purpose of this study was to detect differences in clinical characteristics and
      headache triggers and in a Greek cohort of 51 migraineurs and 12 patients with
      tension-type headache. (TTH) Migraine patients had a significantly lower age at
      headache onset and frequency, higher mean visual analogue scale (VAS) and greater
      maximum duration of headache episodes compared to TTH patients. They did not
      differ from (TTH) patients in quality of headache, laterality of pain, way of
      headache installation and progression and temporal pattern of headaches. Nausea,
      vomiting and phonophobia were more frequent in migraine. Triggering of headaches
      by dietary factors was associated with migraine, whereas there was no difference
      between the two groups in any of the other headache triggers. Stress, both
      physical and psychological, were particularly common in both patient groups. 

PMID- 26222358
TI  - Short-term mortality and prognostic factors related to status epilepticus.
AB  - OBJECTIVE: Status epilepticus (SE) is associated with significant morbidity and
      mortality, and there is some controversy concerning predictive indicators of
      outcome. Our main goal was to determine mortality and to identify factors
      associated with SE prognosis. METHOD: This prospective study in a tertiary-care
      university hospital, included 105 patients with epileptic seizures lasting more
      than 30 minutes. Mortality was defined as death during hospital admission.
      RESULTS: The case-fatality rate was 36.2%, which was higher than in previous
      studies. In univariate analysis, mortality was associated with age, previous
      epilepsy, complex focal seizures; etiology, recurrence, and refractoriness of SE;
      clinical complications, and focal SE. In multivariate analysis, mortality was
      associated only with presence of clinical complications. CONCLUSIONS: Mortality
      associated with SE was higher than reported in previous studies, and was not
      related to age, specific etiology, or SE duration. In multivariate analysis,
      mortality was independently related to occurrence of medical complications.

PMID- 26222359
TI  - Cross-cultural adaptation and validation of the episodic autobiographic memory
      interview for Brazilian Portuguese.
AB  - Episodic memory enables the storage of personal events with specific temporal and
      spatial details, and their retrieval through a sensory experience, usually
      visual, which is called autonoetic consciousness. While, in Brazil, several
      scales for the evaluation of anterograde episodic memory have been validated,
      there is not yet an instrument to assess the episodic autobiographical memory.
      The aim of this study is thus to make a cross-cultural adaptation and validation
      of the Episodic Autobiographic Memory Interview (EAMI) for Brazilian Portuguese.
      Altogether, 11 patients with Alzheimer's disease (AD) and 10 healthy controls
      (CTs) were evaluated. EAMI scores for AD patients were lower than those of CTs,
      and these scores also correlated positively with the Remember-Know coefficient.
      The intraclass correlation coefficient indicated a good inter-rater reliability.
      The Portuguese version of EAMI showed a good reliability and validity, which
      suggests that it is a useful tool for evaluation of autobiographical memory in
      Brazilian patients. 

PMID- 26222360
TI  - Validation and cross-cultural adaptation of sexual dysfunction modified scale in
      multiple sclerosis for Brazilian population.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS). These patients suffer from various comorbidities, including sexual
      dysfunction (SD). The lesions of MS may affect regions of the CNS along the
      pathway of sexual response. The Multiple Sclerosis Intimacy and Sexuality
      Questionnaire-19 (MSISQ-19) is a scale that assesses sexual dysfunction. Adapt
      and validate the MSISQ-19 to Brazilian patients with MS. 204 individuals were
      evaluated, 134 patients with MS and 70 healthy persons for the control group. It
      was determined reproducibility, validity, internal consistency and sensitivity of
      the MSISQ-19-BR. Among patients with MS, 54.3% of male and 71.7% of female
      presented some kind of SD. In the control group the results were 12.5% and 19.5%,
      respectively. The MSISQ-19-BR is reproducible, reliable and valid for the
      Brazilian population and may be used as a tool for assessing the impact of sexual
      dysfunction in patients with MS. 

PMID- 26222361
TI  - Indices of agreement between neurosurgeons and a radiologist in interpreting
      tomography scans in an emergency department.
AB  - The power of interpretation in the analysis of cranial computed tomography (CCT)
      among neurosurgeons and radiologists has rarely been studied. This study aimed to
      assess the rate of agreement in the interpretation of CCTs between neurosurgeons
      and a radiologist in an emergency department. METHOD: 227 CCT were independently
      analyzed by two neurosurgeons (NS1 and NS2) and a radiologist (RAD). The level of
      agreement in interpreting the examination was studied. RESULTS: The Kappa values
      obtained between NS1 and NS2 and RAD were considered nearly perfect and
      substantial agreement. The highest levels of agreement when evaluating
      abnormalities were observed in the identification of tumors, hydrocephalus and
      intracranial hematomas. The worst levels of agreement were observed for
      leukoaraiosis and reduced brain volume. CONCLUSIONS: For diseases in which the
      emergency room procedure must be determined, agreement in the interpretation of
      CCTs between the radiologist and neurosurgeons was satisfactory.

PMID- 26222362
TI  - The influence of enriched environment on spatial memory in Swiss mice of
      different ages.
AB  - The objective of this study was to evaluate the influence of enriched environment
      on spatial memory acquisition in mice of three different age groups. Weanling,
      young, and young adult female Swiss mice were housed in a standard control or
      enriched environment for 50 days, and their spatial memory was tested with the
      Morris Water Maze. We did not observe an experimental effect for spatial memory
      acquisition, and there was neither an effect of time of analysis nor an
      interaction between experimental group and time of analysis. Regarding effects of
      experimental group and training day in relation to latency in finding the hidden
      platform, we did find an effect in the experimental young adult mice group (p =
      0.027), but there was no interaction between these factors in all three groups.
      Based on these findings environmental enrichment did not enhance spatial memory
      acquisition in female Swiss mice in the tested age groups. 

PMID- 26222363
TI  - Advances and new insights in the neuropathogenesis of dengue infection.
AB  - Dengue virus (DENV) infects approximately 390 million persons every year in more
      than 100 countries. Reports of neurological complications are more frequently.
      The objective of this narrative review is to bring up the advances in the dengue
      neuropathogenesis. DENV can access the nervous system through blood-brain barrier
      disturbance mediated by cytokine. The blood-cerebrospinal fluid (CSF) barrier
      seems to be also involved, considering the presence of the virus in the CSF of
      patients with neurological manifestations. As for neurotropism, several studies
      showed the presence of RNA and viral antigens in brain tissue and CSF in humans.
      In murine model, different virus mutations were associated to neurovirulence.
      Despite the advances in the dengue neuropathogenesis, it is still necessary to
      determine a more appropriate animal model and increase the number of cases of
      autopsy. The detection of neurovirulence markers may contribute to establish a
      prognosis, the disease control and vaccine development. 

PMID- 26222364
TI  - Preventing bleeding and thromboembolic complications in atrial fibrillation
      patients undergoing surgery.
AB  - Neurologists feel uneasy when asked about temporary anticoagulant interruption
      for surgery in patients with atrial fibrillation (AF). Rational decisions can be
      made based on current scientific evidence. Method Critical review of
      international guidelines and selected references pertaining to bleeding and
      thromboembolism during periods of oral anticoagulant interruption. Results
      Withholding oral anticoagulants leads to an increased risk of perioperative
      thromboembolism, depending on factors such as age, renal and liver function,
      previous ischemic events, heart failure etc. Surgeries are associated with a
      variable risk of bleeding - from minimal to very high. Individualized decisions
      about preoperative drug suspension, bridging therapy with heparin and time to
      restart oral anticoagulants after hemostasis can significantly reduce these
      opposing risks. Conclusion Rational decisions can be made after discussion with
      all Health care team professionals involved and consideration of patient fears
      and expectations. Formal written protocols should help managing antithrombotic
      treatment during this delicate period. 

PMID- 26222365
TI  - Cortical spreading depression in migraine-time to reconsider?
AB  - New evidence concerning the pathophysiology of migraine has come from the results
      of therapeutic transcranial magnetic stimulation (tTMS). The instantaneous
      responses to single pulses applied during the aura or headache phase, together
      with a number of other observations, make it unlikely that cortical spreading
      depression is involved in migraine. tTMS is considered to act by abolishing
      abnormal impulse activity in cortical pyramidal neurons and a suggestion is made
      as to how this activity could arise. 

PMID- 26222366
TI  - Neurobehavioral disorders locked in Alcatraz: case reports on three famous
      inmates.
AB  - The Alcatraz prison, with its picturesque surroundings and fascinating life
      stories of its inmates, has been the subject of a number of films and
      publications. The authors take a closer look at the biographies of "Al Capone",
      Robert "Birdman" Stroud and "Mickey" Cohen. These legendary American mobsters
      shared not only a history at "The Rock", but also a history of neuropsychiatric
      diseases, ranging from neurosyphilis to anti-social, borderline and obsessive
      compulsive personality disorders.

PMID- 26222367
TI  - Spinocerebellar ataxia type 10 in the South of Brazil: the Amerindian-Belgian
      connection.
AB  - Spinocerebellar ataxia type 10 (SCA10) is a rare form of autosomal dominant
      ataxia found predominantly in patients from Latin America with Amerindian
      ancestry. The authors report the history of SCA10 families from the south of
      Brazil (the states of Parana and Santa Catarina), emphasizing the Belgian
      Amerindian connection. 

PMID- 26222368
TI  - The ear as a diagnostic key in a headache syndrome.

PMID- 26222369
TI  - Professor Leao's original note.

PMID- 26222370
TI  - Correction: PET-CT imaging in a patient with progressive supranuclear palsy.

PMID- 26222371
TI  - A Rare Case of Glomus Jugulare Tumor Presenting as Papilledema.

PMID- 26222373
TI  - Near infrared light-actuated gold nanorods with cisplatin-polypeptide wrapping
      for targeted therapy of triple negative breast cancer.
AB  - Despite considerable progress being made in breast cancer therapy, the complete
      eradication of highly aggressive triple negative breast cancer (TNBC) remains a
      notable challenge today. We herein report on the fabrication of novel gold
      nanorods (GNRs) with covalent cisplatin-polypeptide wrapping and folic acid (FA)
      conjugation (FA-GNR@Pt) for the targeted photothermal (PT) therapy and
      chemotherapy of TNBC. The FA-GNR@Pt hybrid nanoparticles are designed to
      integrate the photothermal conversion property of GNRs, the superior
      biocompatibility of polypeptide poly(l-glutamic acid) (PGA), the chemotoxicity of
      cisplatin, and the tumor targeting ability of FA into one single nanoplatform. In
      combination with localized near infrared (NIR) laser illumination, the resulting
      FA-GNR@Pt hybrid nanoparticles are able to significantly inhibit the growth of
      the TNBC tumor when administered systemically. In particular, they can
      extensively suppress the dissemination of TNBC cells from the primary tumor to
      the lung by eliminating the peripheral tumor blood vessels. Collectively, our
      studies demonstrate that the combined PT therapy and chemotherapy using cisplatin
      loaded GNRs with FA conjugation might imply a promising strategy for targeted
      treatment of TNBC. 

PMID- 26222374
TI  - Composition-dependent band gaps and indirect-direct band gap transitions of group
      IV semiconductor alloys.
AB  - We used the coherent potential approximation to investigate the band structures
      of group-IV semiconductor alloys, including Si(x)Ge(1-x), Ge(1-y)Sn(y) and
      Si(x)Ge(1-x-y)Sn(y). The calculations for Si(x)Ge(1-x) prove the reliability and
      accuracy of the method we used. For Ge(1-y)Sn(y), the direct band gap optical
      bowing parameter we obtained is 2.37 eV and the indirect-direct band gap
      transition point is at y = 0.067, both consistent with the existing experimental
      data. For Si(x)Ge(1-x-y)Sn(y), with the increase of the Si concentration, the
      compositional dependency of the band gap becomes complex. An indirect-direct band
      gap transition is found in Si(x)Ge(1-x-y)Sn(y) in the range of 0 < x<= 0.20, and
      the indirect-direct crossover line in the compositional space has the quadratic
      form of y = 3.4x(2) + 1.11x + 0.07, not the linear form as suggested before.
      Furthermore, for the Ge lattice-matched alloy Ge(1-x()Si0.79Sn0.21)(X), our
      results show that those with 0.18 < X < 0.253 have band gaps larger than 0.8 eV
      at room temperature.

PMID- 26222375
TI  - Anti-inflammatory and anti-arthritic activity of aqueous extract of Rosa
      centifolia in experimental rat models.
AB  - AIM: The present study was carried out to evaluate the anti-inflammatory and
      antiarthritic activity of Rosa centifolia aqueous extract (RC) in a carrageenan
      induced paw edema model and complete Freund's adjuvant (CFA)-induced arthritis.
      METHODS: Anti-inflammatory activity of RC was evaluated using the carrageenan
      induced paw edema model in rats. Arthritis was induced in rats by sub-plantar
      administration of CFA. Joint size was measured at regular intervals by using a
      micrometer screw gauge. Serum and ankle joints of rats immunized with CFA were
      collected and subjected to enzyme-linked immunosorbent assay for estimation of
      tumor necrosis factor (TNF)-alpha level and dot blot for secretory cytokines
      interleukin (IL)-1beta and IL-6. An acute and 28-day oral toxicity study was
      carried out to evaluate the safety of the test drug. RESULTS: Pre-treatment with
      RC produced a dose-dependent reduction in carrageenan-induced paw edema and CFA
      induced arthritis models and was effective as indomethacin. RC also inhibited the
      delayed increase in joint diameter as seen in control and indomethacin-treated
      animals in CFA-induced arthritis. The expression of proinflammatory mediators TNF
      alpha, IL-6 and IL-1beta was also found to be less in the RC-treated group as
      compared to controls. CONCLUSION: Based on these results, it was suggested that
      Rosa centifolia could be considered as a potential anti-inflammatory and anti
      arthritic agent.

PMID- 26222376
TI  - Mucolytic agents versus placebo for chronic bronchitis or chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary
      disease (COPD) may suffer recurrent exacerbations with an increase in volume or
      purulence of sputum, or both. Personal and healthcare costs associated with
      exacerbations indicate that any therapy that reduces the occurrence of
      exacerbations is useful. A marked difference among countries in terms of
      prescribing of mucolytics reflects variation in perceptions of their
      effectiveness. OBJECTIVES: Primary objective* To determine whether treatment with
      mucolytics reduces frequency of exacerbations and/or days of disability in
      patients with chronic bronchitis or chronic obstructive pulmonary disease.
      Secondary objectives* To assess whether mucolytics lead to improvement in lung
      function or quality of life.* To determine frequency of adverse effects
      associated with use of mucolytics. SEARCH METHODS: We searched the Cochrane
      Airways Group Specialised Register and reference lists of articles on 10 separate
      occasions, most recently in July 2014. SELECTION CRITERIA: We included randomised
      studies that compared oral mucolytic therapy versus placebo for at least two
      months in adults with chronic bronchitis or COPD. We excluded studies of people
      with asthma and cystic fibrosis. DATA COLLECTION AND ANALYSIS: This review
      analysed summary data only, most derived from published studies. For earlier
      versions, one review author extracted data, which were rechecked in subsequent
      updates. In later versions, review authors double-checked extracted data and then
      entered data into RevMan for analysis. MAIN RESULTS: We added four studies for
      the 2014 update. The review now includes 34 trials, recruiting a total of 9367
      participants. Many studies did not clearly describe allocation concealment; hence
      selection bias may have inflated the results, which reduces our confidence in the
      findings.Results of 26 studies with 6233 participants show that the likelihood
      that a patient could be exacerbation-free during the study period was greater
      among mucolytic groups (Peto odds ratio (OR) 1.75, 95% confidence interval (CI)
      1.57 to 1.94). However, more recent studies show less benefit of treatment than
      was reported in earlier studies in this review. The overall number needed to
      treat with mucolytics for an additional beneficial outcome for an average of 10
      months - to keep an additional participant free from exacerbations - was eight
      (NNTB 8, 95% CI 7 to 10). Use of mucolytics was associated with a reduction of
      0.03 exacerbations per participant per month (mean difference (MD) -0.03, 95% CI 
      0.04 to -0.03; participants = 7164; studies = 28; I(2) = 85%) compared with
      placebo, that is, about 0.36 per year, or one exacerbation every three years.
      Very high heterogeneity was noted for this outcome, so results need to be
      interpreted with caution. The type or dose of mucolytic did not seem to alter the
      effect size, nor did the severity of COPD, including exacerbation history. Longer
      studies showed smaller effects of mucolytics than were reported in shorter
      studies.Mucolytic use was associated with a reduction of 0.43 days of disability
      per participant per month compared with placebo (95% CI -0.56 to -0.30; studies =
      13; I(2) = 61%). With mucolytics, the number of people with one or more
      hospitalisations was reduced, but study results were not consistent (Peto OR
      0.68, 95% CI 0.52 to 0.89; participants = 1788; studies = 4; I(2) = 58%).
      Investigators reported improved quality of life with mucolytics (MD -2.64, 95% CI
      -5.21 to -0.08; participants = 2231; studies = 5; I(2) = 51%). Although this mean
      difference did not reach the minimal clinically important difference of -4 units,
      we cannot assess the population impact, as we do not have the data needed to
      carry out a responder analysis. Mucolytic treatment was not associated with any
      significant increase in the total number of adverse effects, including mortality
      (Peto OR 1.03, 95% CI 0.52 to 2.03; participants = 2931; studies = 8; I(2) = 0%),
      but the confidence interval is too wide to confirm that the treatment has no
      effect on mortality. AUTHORS' CONCLUSIONS: In participants with chronic
      bronchitis or COPD, we are moderately confident that treatment with mucolytics
      may produce a small reduction in acute exacerbations and a small effect on
      overall quality of life. Our confidence in the results is reduced by the fact
      that effects on exacerbations shown in early trials were larger than those
      reported by more recent studies, possibly because the earlier smaller trials were
      at greater risk of selection or publication bias, thus benefits of treatment may
      not be as great as was suggested by previous evidence.

PMID- 26222377
TI  - Antiangiogenic Eye Gene Therapy.
AB  - The idea of treating disease in humans with genetic material was conceived over
      two decades ago and with that a promising journey involving development and
      efficacy studies in cells and animals of a large number of novel therapeutic
      reagents unfolded. In the footsteps of this process, successful gene therapy
      treatment of genetic conditions in humans has shown clear signs of efficacy.
      Notably, significant advancements using gene supplementation and silencing
      strategies have been made in the field of ocular gene therapy, thereby
      pinpointing ocular gene therapy as one of the compelling "actors" bringing gene
      therapy to the clinic. Most of all, this success has been facilitated because of
      (1) the fact that the eye is an effortlessly accessible, exceedingly
      compartmentalized, and immune-privileged organ offering a unique advantage as a
      gene therapy target, and (2) significant progress toward efficient, sustained
      transduction of cells within the retina having been achieved using nonintegrating
      vectors based on recombinant adeno-associated virus and nonintegrating lentivirus
      vectors. The results from in vivo experiments and trials suggest that treatment
      of inherited retinal dystrophies, ocular angiogenesis, and inflammation with gene
      therapy can be both safe and effective. Here, the progress of ocular gene therapy
      is examined with special emphasis on the potential use of RNAi- and protein-based
      antiangiogenic gene therapy to treat exudative age-related macular degeneration. 

PMID- 26222378
TI  - Comparison of visual receptive field properties of the superior colliculus and
      primary visual cortex in rats.
AB  - The rat visual system comprises cortical and subcortical pathways. The receptive
      field properties of cells in the visual cortex have been extensively studied;
      however, the fundamental roles of the two circuits in visual information
      processing are not well understood. To address this question, we have applied
      quantitative methods to compare and characterize the spatiotemporal receptive
      field (RF) properties of neurons in primary visual cortex (V1) cells and
      superficial layers of the superior colliculus (SC) in rats by means of
      extracellular recordings. An analysis of visual stimulus processing revealed
      distinct functional characteristics of the two visual circuits. RF diameters of
      SC neurons were significantly larger than those of V1 cells. Most cells in both
      regions had high orientation selectivity, but the mean orientation bandwidth of
      the SC was broader than that of V1 cells (101.5 degrees  vs. 60.2 degrees ). The
      mean optimal spatial frequency (SF) of SC cells was lower but had a broader
      bandwidth than that of V1 cells (0.03 vs. 0.068 cpd). The majority of SC and V1
      cells (70% and 68%, respectively) had RFs with band-pass temporal frequency (TF)
      tuning profiles and similar optimal TFs. However, temporal band-pass profiles of
      the SC showed narrower mean temporal bandwidths than those of V1 cells (1.42 vs.
      2.36 octaves). The majority of neurons in visual cortical and subcortical
      structures were activated in response to high-contrast, drifting gratings in the
      preferred orientation. The percentage of V1 neurons with a low-contrast threshold
      was larger than the proportion of SC neurons (45.6% vs. 30%), indicating that the
      former adapt better to contrast. The substantial overlap in latency distributions
      between SC and V1 areas suggests that the two visual systems process and analyze
      visual signals in parallel. However, the two areas use different neural encoding
      mechanisms based on different latency distribution trends. These results indicate
      that SC cells have poor spatial acuity and are better suited to detecting high
      contrast, moving stimuli in larger visual fields. In contrast, V1 cells are
      adapted to extracting shape information and detailed features of objects.

PMID- 26222379
TI  - Photodynamic inactivation of Escherichia coli with cationic ammonium Zn(II)
      phthalocyanines.
AB  - The aim of this work was the development of a family of novel water soluble
      Zinc(II) phthalocyanines (Pc) for the photodynamic inactivation of Gram-negative
      bacteria. Pc derivatives 1a, 2a and 3a containing trimethylammonium groups with
      varied number and nature of the groups at peripheral positions were synthesized
      by cyclotetramerization of dimethyl amino substituted phthalonitriles in the
      presence of zinc powder, using 1-chloronaphthalene as a solvent, followed by
      cationization using dimethyl sulfate. The solubility, singlet oxygen generation
      ((1)O2) and stability/photostability of each Pc were evaluated as well as the
      affinity to bacterial cells and their photosensitizing potential against a
      recombinant bioluminescent Escherichia coli strain, used as a biological model
      for Gram negative bacteria. The efficiency of photodynamic inactivation was
      assessed under white and red light at an irradiance of 150 mW cm(-2). All Pc were
      soluble in phosphate buffer saline and in dimethyl sulfoxide and demonstrated
      good stability/photostability. The photochemical parameters reveal that Pc 2a and
      3a are more efficient singlet oxygen producers than Pc 1a, for which singlet
      oxygen generation could not be demonstrated. Pc 2a and 3a caused
      photosensitization in E. coli. The inactivation factors attained with red light
      were, however, generally higher than those with white light. Under red light Pc
      3a and 2a caused, respectively, 5.6 and 4.9 log reduction in the bioluminescence
      of the E. coli while, with white light, the corresponding inactivation factors
      were 2.5 and 0.5 log. The order of the PDI efficiency (3a > 2a ? 1a) was
      determined by the combined effect of solubility, singlet oxygen generation
      ability and affinity to bacterial cells. Ammonium phthalocyanines with eight
      charges or containing halogen atoms such as chlorine, when irradiated with red
      light can, therefore, be regarded as promising photosensitizers for the
      inactivation of Gram-negative bacteria.

PMID- 26222381
TI  - Ebola in the United States--Public Reactions and Implications.

PMID- 26222380
TI  - Effect of Cranial Window Diameter During Deep Brain Stimulation Surgery on Volume
      of Pneumocephalus.
AB  - OBJECTIVE: Successful deep brain stimulation (DBS) surgery necessitates high
      accuracy in targeting specific intracranial nuclei. Brain shift due to
      pneumocephalus can contribute to decreased accuracy. Larger burr holes and dural
      openings may increase pneumocephalus volume due to a greater degree of
      communication between the subdural space and extracranial air. The aim of this
      study is to determine if there is a statistically and clinically significant
      difference in postoperative pneumocephalus volume related to burr hole and
      durotomy size. MATERIALS AND METHODS: DBS electrodes were surgically implanted
      through either large (14 mm) burr holes or small (4 mm) twist drill holes.
      Immediate postoperative computerized tomography (CT) scans of 165 electrode
      implantations in 85 patients from 2010 to 2013 were retrospectively analyzed.
      Student's t-test and Mann-Whitney U-test were employed with a threshold of
      significance set at p <= 0.05. RESULTS: No significant difference in
      pneumocephalus was identified between patients who had implantation of DBS
      electrodes through 4 mm twist drill holes (N = 71 hemispheres, 12.84 +/- 9.79
      cm(3) ) and those with large 14 mm burr holes (N = 87, 11.70 +/- 7.46 cm(3) , p =
      0.42). Volume of pneumocephalus did not correlate with duration of surgery or
      patient age. The groups did not differ significantly with respect to other
      aspects of surgical implantation technique or surgical duration. CONCLUSION:
      While identifying factors that may reduce pneumocephalus volume may be critical
      to improving stereotactic accuracy and targeting, the current results suggest
      that burr hole size may not alter the degree of brain shift.

PMID- 26222382
TI  - Community Trust and the Ebola Endgame.

PMID- 26222383
TI  - The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome.
AB  - Gastric acidity is likely a key factor shaping the diversity and composition of
      microbial communities found in the vertebrate gut. We conducted a systematic
      review to test the hypothesis that a key role of the vertebrate stomach is to
      maintain the gut microbial community by filtering out novel microbial taxa before
      they pass into the intestines. We propose that species feeding either on carrion
      or on organisms that are close phylogenetic relatives should require the most
      restrictive filter (measured as high stomach acidity) as protection from foreign
      microbes. Conversely, species feeding on a lower trophic level or on food that is
      distantly related to them (e.g. herbivores) should require the least restrictive
      filter, as the risk of pathogen exposure is lower. Comparisons of stomach acidity
      across trophic groups in mammal and bird taxa show that scavengers and carnivores
      have significantly higher stomach acidities compared to herbivores or carnivores
      feeding on phylogenetically distant prey such as insects or fish. In addition, we
      find when stomach acidity varies within species either naturally (with age) or in
      treatments such as bariatric surgery, the effects on gut bacterial pathogens and
      communities are in line with our hypothesis that the stomach acts as an
      ecological filter. Together these results highlight the importance of including
      measurements of gastric pH when investigating gut microbial dynamics within and
      across species. 

PMID- 26222385
TI  - Clinical trial success rates of anti-obesity agents: the importance of
      combination therapies.
AB  - The objective of this study was to construct a clinical trial profile assessing
      the risk of drug failure among anti-obesity agents. Research was conducted by
      looking at anti-obesity therapies currently on the market or in clinical trials
      (phases I to III) conducted from 1998 to September 2014, with the exclusion of
      any drugs whose phase I trial was conducted prior to January 1998. This was
      completed primarily through a search on http://clinicaltrials.gov where a total
      of 51 drugs met the search criteria. The transition probabilities were then
      calculated based on various classifications and compared against industry
      standards. The transition probability of anti-obesity agents was 8.50% whereas
      the transition probability of industry standards was 10.40%. Combination
      therapies had four times the transition probability than monotherapies, 40% and
      4.75%, respectively. Therefore, it was determined that 92% of drugs fail during
      clinical trial testing for this indication and combination therapy appears to
      improve clinical trial success rates to 10-fold. 

PMID- 26222386
TI  - Migration and isolation during the turbulent Ponto-Caspian Pleistocene create
      high diversity in the crustacean Paramysis lacustris.
AB  - The Ponto-Caspian brackish-water fauna inhabits estuaries and rivers of the
      Black, Azov and Caspian seas and is fragmented by higher salinity waters and a
      major interbasin watershed. The fauna is known for the high levels of endemism,
      complex zoogeographic histories, and as a recent source of successful invasive
      species. It remains debated whether the Black and Azov Sea brackish-water
      populations survived unfavourable Pleistocene conditions in multiple separate
      refugia or whether the two seas were (repeatedly) recolonized from the Caspian.
      Using microsatellite and mtDNA markers, we demonstrate deep among- and within
      basin subdivisions in a widespread Ponto-Caspian mysid crustacean Paramysis
      lacustris. Five genetic clusters were identified, but their relationships did not
      reflect the geography of the region. The Azov cluster was the most distinct (4-5%
      COI divergence), despite its geographic position in the corridor between Black
      and Caspian seas, and may represent a new species. In the northern Black Sea
      area, the Dnieper cluster was closer to the Caspian cluster than to the
      neighbouring Danube-Dniester-Bug populations, suggesting separate colonizations
      of the Black Sea. Overall, the data implied a predominant gene flow from the east
      to the Black Sea and highlight the importance of Caspian Sea transgressions in
      facilitating dispersal. Yet, the presence of distinct lineages in the Black Sea
      points to the persistence of isolated refugial populations that have gained
      diagnostic differences under presumably high mutation rates and large population
      sizes. The unfavourable Pleistocene periods in the Black Sea therefore appear to
      have promoted diversification of the brackish-water lineages, rather than
      extirpated them. 

PMID- 26222384
TI  - Pluronics-Formulated Farnesol Promotes Efficient Killing and Demonstrates Novel
      Interactions with Streptococcus mutans Biofilms.
AB  - Streptococcus mutans is the primary causative agent of dental caries, one of the
      most prevalent diseases in the United States. Previously published studies have
      shown that Pluronic-based tooth-binding micelles carrying hydrophobic
      antimicrobials are extremely effective at inhibiting S. mutans biofilm growth on
      hydroxyapatite (HA). Interestingly, these studies also demonstrated that non
      binding micelles (NBM) carrying antimicrobial also had an inhibitory effect,
      leading to the hypothesis that the Pluronic micelles themselves may interact with
      the biofilm. To explore this potential interaction, three different S. mutans
      strains were each grown as biofilm in tissue culture plates, either untreated or
      supplemented with NBM alone (P85), NBM containing farnesol (P85F), or farnesol
      alone (F). In each tested S. mutans strain, biomass was significantly decreased
      (SNK test, p < 0.05) in the P85F and F biofilms relative to untreated biofilms.
      Furthermore, the P85F biofilms formed large towers containing dead cells that
      were not observed in the other treatment conditions. Tower formation appeared to
      be specific to formulated farnesol, as this phenomenon was not observed in S.
      mutans biofilms grown with NBM containing triclosan. Parallel CFU/ml
      determinations revealed that biofilm growth in the presence of P85F resulted in a
      3-log reduction in viability, whereas F decreased viability by less than 1-log.
      Wild-type biofilms grown in the absence of sucrose or gtfBC mutant biofilms grown
      in the presence of sucrose did not form towers. However, increased cell killing
      with P85F was still observed, suggesting that cell killing is independent of
      tower formation. Finally, repeated treatment of pre-formed biofilms with P85F was
      able to elicit a 2-log reduction in viability, whereas parallel treatment with F
      alone only reduced viability by 0.5-log. Collectively, these results suggest that
      Pluronics-formulated farnesol induces alterations in biofilm architecture,
      presumably via interaction with the sucrose-dependent biofilm matrix, and may be
      a viable treatment option in the prevention and treatment of pathogenic plaque
      biofilms. 

PMID- 26222387
TI  - Tunable Optical Excitations in Twisted Bilayer Graphene Form Strongly Bound
      Excitons.
AB  - When two sheets of graphene stack in a twisted bilayer graphene (tBLG)
      configuration, the resulting constrained overlap between interplanar 2p orbitals
      produce angle-tunable electronic absorption resonances. By applying a novel
      combination of multiphoton transient absorption (TA) microscopy and TEM, we
      resolve the electronic structure and ensuing relaxation by probing resonant
      excitations of single tBLG domains. Strikingly, we find that the transient
      electronic population in resonantly excited tBLG domains is enhanced many fold,
      forming a major electronic relaxation bottleneck. Two-photon TA microscopy shows
      this bottleneck effect originates from a strongly bound, dark exciton state lying
      ~0.37 eV below the 1-photon absorption resonance. This stable coexistence of
      strongly bound excitons alongside free-electron continuum states has not been
      previously observed in a metallic, 2D material. 

PMID- 26222388
TI  - Health Care Access and Utilization Among Adults Aged 18-64, by Race and Hispanic
      Origin: United States, 2013 and 2014.
AB  - In 2014, U.S. adults could buy a private health insurance plan through the Health
      Insurance Marketplace or state-based exchanges established as part of the
      Affordable Care Act. Moreover, some states opted to expand Medicaid coverage to
      low-income adults. Data from the 2013 and 2014 National Health Interview Survey
      (NHIS) are used to describe recent changes in health insurance coverage and
      selected measures of health care access and utilization for adults aged 18-64, by
      race and Hispanic origin.

PMID- 26222389
TI  - World Input-Output Network.
AB  - Production systems, traditionally analyzed as almost independent national
      systems, are increasingly connected on a global scale. Only recently becoming
      available, the World Input-Output Database (WIOD) is one of the first efforts to
      construct the global multi-regional input-output (GMRIO) tables. By viewing the
      world input-output system as an interdependent network where the nodes are the
      individual industries in different economies and the edges are the monetary goods
      flows between industries, we analyze respectively the global, regional, and local
      network properties of the so-called world input-output network (WION) and
      document its evolution over time. At global level, we find that the industries
      are highly but asymmetrically connected, which implies that micro shocks can lead
      to macro fluctuations. At regional level, we find that the world production is
      still operated nationally or at most regionally as the communities detected are
      either individual economies or geographically well defined regions. Finally, at
      local level, for each industry we compare the network-based measures with the
      traditional methods of backward linkages. We find that the network-based measures
      such as PageRank centrality and community coreness measure can give valuable
      insights into identifying the key industries. 

PMID- 26222390
TI  - Opposite Effects of Early-Life Competition and Developmental Telomere Attrition
      on Cognitive Biases in Juvenile European Starlings.
AB  - Moods are enduring affective states that we hypothesise should be affected by an
      individual's developmental experience and its current somatic state. We tested
      whether early-life adversity, induced by manipulating brood size, subsequently
      altered juvenile European starlings' (Sturnus vulgaris) decisions in a judgment
      bias task designed to provide a cognitive measure of mood. We predicted that
      starlings from larger broods, specifically those that had experienced more nest
      competitors larger than themselves would exhibit reduced expectation of reward,
      indicative of a 'pessimistic', depression-like mood. We used a go/no-go task, in
      which 30 starlings were trained to probe a grey card disc associated with a
      palatable mealworm hidden underneath and avoid a different shade of grey card
      disc associated with a noxious quinine-injected mealworm hidden underneath.
      Birds' response latencies to the trained stimuli and also to novel, ambiguous
      stimuli intermediate between these were subsequently tested. Birds that had
      experienced greater competition in the nest were faster to probe trained stimuli,
      and it was therefore necessary to control statistically for this difference in
      subsequent analyses of the birds' responses to the ambiguous stimuli. As
      predicted, birds with more, larger nest competitors showed relatively longer
      latencies to probe ambiguous stimuli, suggesting reduced expectation of reward
      and a 'pessimistic', depression-like mood. However, birds with greater
      developmental telomere attrition--a measure of cellular aging associated with
      increased morbidity and reduced life-expectancy that we argue could be used as a
      measure of somatic state--showed shorter latencies to probe ambiguous stimuli.
      This would usually be interpreted as evidence for a more positive or 'optimistic'
      affective state. Thus, increased competition in the nest and poor current somatic
      state appear to have opposite effects on cognitive biases. Our results lead us to
      question whether increased expectation of reward when presented with ambiguous
      stimuli always indicates a more positive affective state. We discuss the
      possibility that birds in poor current somatic state may adopt a 'hungry'
      cognitive phenotype that could drive behaviour commonly interpreted as 'optimism'
      in food-rewarded cognitive bias tasks.

PMID- 26222391
TI  - Guideline-based development of quality indicators for prevention and management
      of postpartum hemorrhage.
AB  - INTRODUCTION: To systematically develop a set of guideline-based quality
      indicators for postpartum hemorrhage (PPH) as a tool to measure guideline
      adherence in actual PPH care. MATERIAL AND METHODS: A Rand-modified Delphi
      procedure was used to systematically achieve consensus among a panel of 22
      experts on PPH care on recommendations extracted from evidence-based guidelines,
      Managing-Obstetrics-Emergencies-Trauma (MOET) instructions and international
      literature. The selected recommendations were individually rated on health gain
      (prevention of maternal mortality and morbidity) and overall efficiency by the
      expert panel. Subsequently, consensus about the most important recommendations to
      measure quality of PPH care among the panel members was reached, followed by a
      final approval. Last, definition of the final set by critical appraisal of the
      recommendations regarding measurability took place. The main outcome measure was
      a set of valid quality indicators for prevention and management of PPH. RESULTS:
      From the 69 extracted recommendations, 50 were selected and translated into 22
      quality indicators on professional performance (n = 17) and organization of PPH
      care (n = 5). The professional performance indicators covered all fields of PPH
      care, such as prevention (n = 2) and management of PPH, including communication
      and documentation (n = 4), monitoring and prevention of shock (n = 3), use of
      blood products (n = 3) and treatment of PPH (n = 5). Organizational indicators (n
      = 5) were clustered into protocols and agreements, audit, accessibility and
      documentation. CONCLUSIONS: This study describes a stepwise systematic
      development of 22 performance and organizational indicators to use for measuring
      the whole care process of prevention and management of PPH.

PMID- 26222392
TI  - Mammary-Derived Growth Inhibitor Targeting Peptide-Modified PEG-PLA Nanoparticles
      for Enhanced Targeted Glioblastoma Therapy.
AB  - Targeting delivery of chemotherapeutics to neovasculature represents a promising
      means for tumor therapy since angiogenesis has been a featured hallmark of
      glioblastma. However, anti-angiogenic therapy would induce the occurrence of
      metastatic tumor and even neoplasm recurrence. Simultaneous targeting of tumor
      cells and neovasculature perfectly overcome such defects and has been proven to
      be an efficacious strategy for suppressing tumor growth. In the present study, a
      tumor homing peptide CooP selective binding to mammary-derived growth inhibitor
      that overexpressed in glioma cells and blood vessel endothelial cells was
      decorated on the surface of paclitaxel-loading PEG-PLA nanoparticles (NP-PTX) to
      obtain the dual targeting nanovector CooP-NP-PTX. In vitro antiproliferation
      study showed that HUVEC cells and U87MG cells were much more sensitive to CooP-NP
      PTX than NP-PTX. In vivo imaging demonstrated that CooP-NP accumulated more
      selectively and penetrated deeper into the tumor site. In addition, the glioma
      bearing mice treated with CooP-NP-PTX achieved the longest survival time compared
      to NP-PTX and Taxol. The findings observed above indicated that CooP peptide
      functionalized anti-neoplastic agent-loaded nanoparticles might possess promising
      potential for glioblastoma therapy. 

PMID- 26222394
TI  - Is it time for videolaryngoscopy to be the standard of care?

PMID- 26222393
TI  - Risk factors of post-dural puncture headache receiving a blood patch in obstetric
      patients.
AB  - BACKGROUND: Post-dural puncture headache (PDPH) is one of the most frequent
      complications of neuraxial anesthesia and analgesia. The objective is to
      determine risk factors of PDPH receiving a blood patch in the obstetric
      population. METHODS: Between November 2009 and January 2013, 10914 women
      delivered in Port Royal maternity unit (Paris, France). The incidence of PDPH
      receiving a blood patch was calculated among those who received neuraxial
      analgesia or anesthesia for delivery. Then we performed a case-control study to
      identify risk factors for PDPH receiving a blood patch by comparing women who
      experienced PDPH receiving a blood patch with some women randomly selected by
      computer among those who delivered during the study period (4 controls for 1
      case, univariate and multivariate analysis). RESULTS: Among the 10685 women who
      had neuraxial analgesia or anesthesia, 0.4% had a PDPH receiving a blood patch.
      In the univariate analysis, cervix dilatation >=7 cm, lateral decubitus position
      during the neuraxial procedure and multiple punctures were significantly
      associated with PDPH receiving a blood patch, whereas maternal Body Mass Index,
      age, mode of delivery, performance at night and level of needle insertion were
      not. In the multivariate analysis, cervix dilatation >=7 cm and multiple
      punctures significantly increased the risk of PDPH receiving a blood patch (odd
      ratios 6.5 [95% CI: 1.5-29.3] and 5.6 [95% CI: 2.2-14.0], respectively).
      Experience of the anesthesiologist was not associated with PDPH in both
      univariate and multivariate analysis. CONCLUSIONS: In the obstetric population, a
      cervix dilation >=7 cm during labor and multiple punctures are independent risk
      factors for PDPH receiving a blood patch.

PMID- 26222395
TI  - The end of an era of pharmaconutrition and immunonutrition trials for the
      critically-ill patient?

PMID- 26222396
TI  - Anti-N-metil-D-aspartate receptor encephalitis: a challenge for intensivists.

PMID- 26222397
TI  - Cross-Linking the Fibers of Supramolecular Gels Formed from a Tripodal
      Terpyridine Derived Ligand with d-Block Metal Ions.
AB  - The tripodal terpyridine ligand, L, forms 1D helical supramolecular polymers/gels
      in H2O-CH3OH solution mediated through hydrogen bonding and pi-pi interactions.
      These gels further cross-link into 3D supramolecular metallogels with a range of
      metal ions (M) such as Fe(II), Ni(II), Cu(II), Zn(II), and Ru(III); the cross
      linking resulting in the formation of colored or colorless gels. The fibrous
      morphology of these gels was confirmed using scanning electron microscopy (SEM);
      while the self-assembly processes between L and M were investigated by absorbance
      and emission spectroscopy from which their binding constants were determined by
      using a nonlinear regression analysis. 

PMID- 26222398
TI  - Poly(Lactic Acid) Hemodialysis Membranes with Poly(Lactic Acid)-block-Poly(2
      Hydroxyethyl Methacrylate) Copolymer As Additive: Preparation, Characterization,
      and Performance.
AB  - Poly(lactic acid) (PLA) hemodialysis membranes with enhanced antifouling
      capability and hemocompatibility were developed using poly(lactic acid)-block
      poly(2-hydroxyethyl methacrylate) (PLA-PHEMA) copolymers as the blending
      additive. PLA-PHEMA block copolymers were synthesized via reversible addition
      fragmentation (RAFT) polymerization from aminolyzed PLA. Gel permeation
      chromatography (GPC) and (1)H-nuclear magnetic resonance ((1)H NMR) were applied
      to characterize the synthesized products. By blending PLA with the amphiphilic
      block copolymer, PLA/PLA-PHEMA membranes were prepared by nonsolvent induced
      phase separation (NIPS) method. Their chemistry and structure were characterized
      with X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM)
      and atomic force microscopy (AFM). The results revealed that PLA/PLA-PHEMA
      membranes with high PLA-PHEMA contents exhibited enhanced hydrophilicity, water
      permeability, antifouling and hemocompatibility. Especially, when the PLA-PHEMA
      concentration was 15 wt %, the water flux of the modified membrane was about 236
      L m(-2) h(-1). Its urea and creatinine clearance was more than 0.70 mL/min,
      lysozyme clearance was about 0.50 mL/min, BSA clearance was as less as 0.31
      mL/min. All the results suggest that PLA-PHEMA copolymers had served as effective
      agents for optimizing the property of PLA-based membrane for hemodialysis
      applications. 

PMID- 26222404
TI  - Synthesis of Tumor-Associated Le(a)Le(x) Hexasaccharides: Instability of a Thiol
      Containing Oligosaccharide in Mass Spectrometry and Hypermetalation Detected by
      ESI FAIMS.
AB  - We report the efficient synthesis of three analogues of the tumor-associated
      carbohydrate antigen Le(a)Le(x). This hexasaccharide was prepared as a soluble
      inhibitor hexyl glycoside, as a 6-aminohexyl glycoside for conjugation to
      proteins, and as a 6-thiohexyl glycoside for immobilization to a gold surface.
      These three analogues were obtained from a common hexasaccharide intermediate and
      isolated pure following efficient deprotection reactions that involved metal
      dissolving conditions. While all other intermediates and analogues gave the
      expected molecular ions in ESI HRMS, the 6-thiohexyl glycoside final compound
      gave a complex spectrum in which no signal matched the molecular ion. Using ESI
      FAIMS HRMS, we were able to prevent ion dissociation reactions and obtained high
      quality spectral data. The ions detected could be characterized unambiguously
      from their accurate masses and gave insight into the behavior of the thiohexyl
      analogue in the gas phase. These results indicate that the 6-thiohexyl glycoside
      lost water and led to the formation of "hypermetalated" species which we propose
      are cyclic. 

PMID- 26222406
TI  - Iontophoresis of minoxidil sulphate loaded microparticles, a strategy for
      follicular drug targeting?
AB  - The feasibility of targeting drugs to hair follicles by a combination of
      microencapsulation and iontophoresis has been evaluated. Minoxidil sulphate
      (MXS), which is used in the treatment of alopecia, was selected as a relevant
      drug with respect to follicular penetration. The skin permeation and disposition
      of MXS encapsulated in chitosan microparticles (MXS-MP) was evaluated in vitro
      after passive and iontophoretic delivery. Uptake of MXS was quantified at
      different exposure times in the stratum corneum (SC) and hair follicles.
      Microencapsulation resulted in increased (6-fold) drug accumulation in the hair
      follicles relative to delivery from a simple MXS solution. Application of
      iontophoresis enhanced follicular delivery for both the solution and the
      microparticle formulations. It appears, therefore, that microencapsulation and
      iontophoresis can act synergistically to enhance topical drug targeting to hair
      follicles. 

PMID- 26222405
TI  - Bacteria and osteoblast adhesion to chitosan immobilized titanium surface: A race
      for the surface.
AB  - In order to evaluate the anti-infective efficacy of the titanium implant
      materials, two co-culture systems, a low-bacteria/osteoblast (L-B) and a high
      bacteria/osteoblast system (H-B), were established. Untreated (UN-Ti), sulfuric
      acid-treated (SA-Ti), and chitosan immobilized titanium (SA-CS-Ti) materials were
      developed and evaluated. Bacteria and osteoblast behaviors, including initial
      attachment (evaluated at 30 mins), adhesion (evaluated at 4 h), and osteoblast
      spreading on each material surface were evaluated using quantification assays,
      scanning electron microscopy (SEM), and confocal microscopy. Quantification
      analysis at 30 mins showed significantly higher number of osteoblast present on
      SA-CS-Ti in both L-B (10,083 +/- 2626) and H-B (23,592 +/- 2233) than those on
      the UN-Ti (p<0.05). SEM observation and confocal microscopy results showed more
      surface area was occupied by adhered osteoblasts on SA-CS-Ti than UN-Ti and SA-Ti
      in both co-culture systems at 30 mins. At all time points, SA-CS-Ti had the
      lowest level of bacterial adhesion compared to UN-Ti and SA-Ti in both co-culture
      systems. A significantly (p<0.05) lower number of bacteria were recovered from SA
      CS-Ti (2233 +/- 681) in the H-B system compared to UN-Ti (5367 +/- 1662) and SA
      Ti (4533 +/- 680) at 4h. Quantitative and qualitative co-culture results show the
      great potential of chitosan immobilization onto implant materials to prevent
      implant-associated infections.

PMID- 26222407
TI  - Tailoring of chitosan scaffolds with heparin and gamma-aminopropyltriethoxysilane
      for promoting peripheral nerve regeneration.
AB  - Chitosan has been well known for promoting peripheral nerve regeneration,
      however, its effect is still not as good as that of autografts. In this study,
      the feasibility of using negatively charged heparin and positively charged gamma
      aminopropyltriethoxysilane (APTE) treatment as biocompatible modification of
      lyophilized porous chitosanscaffolds was evaluated. The morphology of the
      prepared chitosan scaffolds as a function of treatment with different charged
      molecules showed no significant differences, while a skin-like surface was
      observed for the scaffolds modified with high APTE concentration and heparin. The
      quantitative and qualitative characterization of heparin and amino densities by
      Toluidine Blue O (TBO) and Acid Orange (AO) assays confirmed the successful
      immobilization of heparin and APTE on the chitosan scaffolds. The measurement of
      surface charge densities indicated that the scaffolds treated with APTE showed
      increased charge densities while heparin decreased the cationic charge density.
      Moreover, the fabricated charge processed chitosan scaffolds were stable after
      immersion in phosphate buffer saline for more than ten days. Further on, the
      chitosan scaffolds processed with 2 mg/mL heparin did facilitate the attachment,
      proliferation and maintain the biological function of Schwann cells in vitro. The
      study demonstrates that chitosan scaffolds treated with suitable heparin
      concentration provides an effective selection for biomaterials surface
      modification and shows great potential for the application in peripheral nerve
      regeneration.

PMID- 26222408
TI  - Physicochemical characterization and pharmacological evaluation of ezetimibe-PVP
      K30 solid dispersions in hyperlipidemic rats.
AB  - The aim of this study was to improve the physicochemical properties as well as
      therapeutic efficacy of ezetimibe (EZT), through preparation of the solid
      dispersion (SD). SDs were formulated using polyvinylpyrrolidone K30 (PVP) via
      solvent method. The physicochemical properties along with in vitro drug release
      patterns of the prepared SDs were examined. To estimate the therapeutic
      efficiency of prepared SDs, in vivo studies including measurement of serum lipid
      levels, liver index and histological analysis of the liver tissue in
      hyperlipidemic rats were performed. Differential scanning calorimetry (DSC) and
      powder X-ray diffractometery (PXRD) showed that the drug crystallinity was
      remarkably decreased during preparation process. Faster drug release pattern of
      SDs was proved by in vitro dissolution test. Administration the SD of EZT led to
      a significant decrease in serum total cholesterol (TC) and LDL-C level as well as
      liver index in hyperlipidemic rats (P<0.05) compared to the PM. Furthermore,
      histological analysis of the liver tissue confirmed the improved efficacy of the
      SDs on the liver steatosis. In the present study, we demonstrated that the SDs of
      EZT with improved physicochemical characteristics had favorable effects on liver
      steatosis, liver index and serum lipid levels in the high fat diet-induced
      hyperlipidemic rats. 

PMID- 26222409
TI  - Multifunctional fluorescent magnetic nanoparticles for lung cancer stem cells
      research.
AB  - In this paper, a multifunctional peptide-fluorescent-magnetic nanocomposites
      (Fe3O4@PEI@Cy5.5@PEG@HCBP-1 NPs) was synthesized via a layer-by-layer approach
      for potential application to cancer diagnoses. The multifunctional nanocomposites
      have great dispersibility and homogeneous particle sizes in aqueous solution.
      Meanwhile, it has perfect hemocompatibility and satisfying cytocompatibility in a
      relatively high concentration. Data from in vitro cytotoxicity assay indicated
      that the nanocomposites could recognize the lung cancer stem cells (CSCs)
      specifically and enrich the HCBP-1 positive CSCs from H460 tumor xenografts
      effectively. Additionally, the results of in vivo live fluorescent imaging and
      magnetic resonance imaging (MRI) showed that the nanocomposites could identify
      lung CSCs in tumor xenografts. These results suggested that the nanocomposites
      could be used as a potential cancer diagnostic agent through modifying diverse
      fluorescence dyes and targeting ligands on its surface.

PMID- 26222410
TI  - Interaction of carbohydrate modified boron nitride nanotubes with living cells.
AB  - Boron nitride nanotubes (BNNTs) are composed of boron and nitrogen atoms and they
      show significantly different properties from their carbon analogues (carbon
      nanotubes, CNTs). Due to their unique properties including low electrical
      conductivity, and imaging contrast and neutron capture properties; they can be
      used in biomedical applications. When their use in biological fields is
      considered, the route of their toxic effect should be clarified. Therefore, the
      study of interactions between BNNTs and living systems is important in envisaging
      biological applications at both cellular and sub-cellular levels to fully gain
      insights of their potential adverse effects. In this study, BNNTs were modified
      with lactose, glucose and starch and tested for their cytotoxicity. First, the
      interactions and the behavior of BNNTs with bovine serum albumin (BSA),
      Dulbecco's Modified Eagle's Medium (DMEM) and DMEM/Nutrient Mixture F-12Ham were
      investigated. Thereafter, their cellular uptake and the cyto- and genotoxicity on
      human dermal fibroblasts (HDFs) and adenocarcinoma human alveolar basal
      epithelial cells (A549) were evaluated. HDFs and A549 cells internalized the
      modified and unmodified BNNTs, and BNNTs were found to not cause significant
      viability change and DNA damage. A higher uptake rate of BNNTs by A549 cells
      compared to HDFs was observed. Moreover, a concentration-dependent cytotoxicity
      was observed on A549 cells while they were safer for HDFs in the same
      concentration range. Based on these findings, it can be concluded that BNNTs and
      their derivatives made with biomacromolecules might be good candidates for
      several applications in medicine and biomedical applications. 

PMID- 26222411
TI  - The effect of mouth breathing on chewing efficiency.
AB  - OBJECTIVE: To examine the effect of mouth breathing on chewing efficiency by
      evaluating masticatory variables. MATERIALS AND METHODS: Ten adult nasal
      breathers with normal occlusion and no temporomandibular dysfunction were
      selected. Subjects were instructed to bite the chewing gum on the habitual side.
      While breathing through the mouth and nose, the glucide elution from the chewing
      gum, number of chewing strokes, duration of chewing, and electromyography (EMG)
      activity of the masseter muscle were evaluated as variables of masticatory
      efficiency. RESULTS: The durations required for the chewing of 30, 60, 90, 120,
      180, and 250 strokes were significantly (P < .05) longer while breathing through
      the mouth. There was no significant difference in the glucide elution rate (%)
      for each chewing stroke between nose and mouth breathings. The glucide elution
      rates for 1- and 3-minute chewing were significantly (P < .05) lower while
      breathing through the mouth. However, there was no significant difference in the
      glucide elution rate for 5-minute chewing between nose and mouth breathings.
      While chewing for 1, 3, and 5 minutes, the chewing stroke and EMG activity of the
      masseter muscle were significantly (P < .05) lower during mouth breathing.
      CONCLUSIONS: It takes a longer amount of time to complete chewing to obtain
      higher masticatory efficiency when breathing through the mouth. Therefore, mouth
      breathing will decrease the masticatory efficiency if the duration of chewing is
      restricted in everyday life.

PMID- 26222412
TI  - Comparison between direct vs indirect anchorage in two miniscrew-supported
      distalizing devices.
AB  - OBJECTIVE: To compare two distalizing devices supported by palatal miniscrews,
      the MGBM System (MGBM) and the Distal Screw appliance (DS), in dental Class II
      patients. MATERIALS AND METHODS: Pretreatment (T1) and postdistalization (T2)
      lateral cephalograms of 53 Class II malocclusion subjects were examined. MGBM
      consisted of 29 patients (16 males, 13 females) with a mean pretreatment age of
      12.3 +/- 1.5 years; DS consisted of 24 patients (11 males, 13 females) with a
      mean pretreatment age of 11.3 +/- 1.2 years. The mean distalization time was 6 +/
      2 months for MGBM and 9 +/- 2 months for DS. Initial and final measurements and
      treatment changes were compared by means of a Student's t-test. RESULTS:
      Maxillary superimpositions showed that the maxillary first molar distalized an
      average of 5.5 mm in the MGBM and 3.2 mm in the DS between T1 and T2; distal
      molar tipping was greater in the MGBM (10.3 degrees ) than in the DS (3.0 degrees
      ). First premolar showed a mean mesial movement of 1.4 mm, with a mesial tipping
      of 4.4 degrees  in the MGBM; on the contrary, first premolar showed a distal
      movement of 2.2 mm, with a distal tipping of 6.2 degrees , in the DS.
      CONCLUSIONS: The MGBM system resulted in greater distal molar movement and less
      treatment time, resulting in more efficient movement than was associated with the
      DS; DS showed less molar tipping during distalization.

PMID- 26222414
TI  - Erratum.

PMID- 26222413
TI  - Identification of long noncoding RNAs dysregulated in the midbrain of human
      cocaine abusers.
AB  - Maintenance of the drug-addicted state is thought to involve changes in gene
      expression in different neuronal cell types and neural circuits. Midbrain
      dopamine (DA) neurons in particular mediate numerous responses to drugs of abuse.
      Long noncoding RNAs (lncRNAs) regulate CNS gene expression through a variety of
      mechanisms, but next to nothing is known about their role in drug abuse. The
      proportion of lncRNAs that are primate-specific provides a strong rationale for
      their study in human drug abusers. In this study, we determined a profile of
      dysregulated putative lncRNAs through the analysis of postmortem human midbrain
      specimens from chronic cocaine abusers and well-matched control subjects (n = 11
      in each group) using a custom lncRNA microarray. A dataset comprising 32 well
      annotated lncRNAs with independent evidence of brain expression and robust
      differential expression in cocaine abusers is presented. For a subset of these
      lncRNAs, differential expression was validated by quantitative real-time PCR and
      cellular localization determined by in situ hybridization histochemistry.
      Examples of lncRNAs exhibiting DA cell-specific expression, different subcellular
      distributions, and covariance of expression with known cocaine-regulated protein
      coding genes were identified. These findings implicate lncRNAs in the cellular
      responses of human DA neurons to chronic cocaine abuse. Long noncoding RNAs
      (lncRNAs) regulate the expression of protein-coding genes, but little is known
      about their potential role in drug abuse. In this study, we identified lncRNAs
      differentially expressed in human cocaine abusers' midbrains. One up-regulated
      antisense lncRNA, tumor necrosis factor receptor-associated factor 3-interacting
      protein 2-antisense 1 (TRAF3IP2-AS1), was found predominantly in the nucleus of
      human dopamine (DA) neurons, whereas the related TRAF3IP2 protein-coding
      transcript was distributed throughout these cells. The abundances of these
      transcripts were significantly correlated (left) suggesting that TRAF3IP2-AS1 may
      regulate TRAF3IP2 gene expression, perhaps through local chromatin changes at
      this locus (right). 

PMID- 26222417
TI  - A novel hanging spherical drop system for the generation of cellular spheroids
      and high throughput combinatorial drug screening.
AB  - We propose a novel hanging spherical drop system for anchoring arrays of droplets
      of cell suspension based on the use of biomimetic superhydrophobic flat
      substrates, with controlled positional adhesion and minimum contact with a solid
      substrate. By facing down the platform, it was possible to generate independent
      spheroid bodies in a high throughput manner, in order to mimic in vivo tumour
      models on the lab-on-chip scale. To validate this system for drug screening
      purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was
      tested and compared to cells in 2D culture. The advantages presented by this
      platform, such as feasibility of the system and the ability to control the size
      uniformity of the spheroid, emphasize its potential to be used as a new low cost
      toolbox for high-throughput drug screening and in cell or tissue engineering. 

PMID- 26222418
TI  - Density gradients at hydrogel interfaces for enhanced cell penetration.
AB  - We report that stiffness gradients facilitate infiltration of cells through
      otherwise cell-impermeable hydrogel interfaces. By enabling the separation of
      hydrogel manufacturing and cell seeding, and by improving cell colonization of
      additively manufactured hydrogel elements, interfacial density gradients present
      a promising strategy to progress in the creation of 3D tissue models. 

PMID- 26222419
TI  - Fabrication of biodegradable synthetic perfusable vascular networks via a
      combination of electrospinning and robocasting.
AB  - Biodegradable synthetic vascular networks are produced via the combination of
      robocasting and electrospinning techniques. Preliminary revascularization studies
      using microvascular endothelial cells and human dermal fibroblasts show good
      attachment and uniform distribution within the vascular networks, highlighting
      their potential use in vascular tissue engineering applications. 

PMID- 26222420
TI  - pH- and redox-responsive self-assembly of amphiphilic hyperbranched poly(amido
      amine)s for controlled doxorubicin delivery.
AB  - Vinyl-terminated hyperbranched poly(amido amine)s is obtained by Michael addition
      polymerization of 4-(aminomethyl)piperidine (AMPD) with a double molar N,N
      cystaminebis(acrylamide) (BAC). Then an amphiphilic hyperbranched poly(BAC2
      AMPD1)-PEG is produced via converting the vinyl groups to amines followed by
      PEGylation. Transmission electron microscopy (TEM), dynamic light scattering
      (DLS), and (1)H nuclear magnetic resonance (NMR) results indicate that the
      micelles can be obtained via self-assembly of hyperbranched poly(BAC2-AMPD1)-PEG.
      Further an anti-cancer drug, doxorubicin (DOX), can be loaded into the micelles.
      pH- and redox-response of the micelles of hyperbranched poly(BAC2-AMPD1)-PEG
      without and with DOX are investigated. The results of confocal microscopy and
      flow cytometry reflect that FITC tagged or DOX loaded micelles of hyperbranched
      poly(BAC2-AMPD1)-PEG can enter HepG2 and MCF-7 cells, and DOX can be observed in
      the nucleus of the cells. The cytotoxicity of the micelles without and with DOX
      is evaluated in HepG2 and MCF-7 cells, and the efficacy to kill the cancer cells
      is discussed in comparison with free DOX. 

PMID- 26222421
TI  - Tailoring the surface charge of dextran-based polymer coated SPIONs for modulated
      stem cell uptake and MRI contrast.
AB  - Tracking stem cells in vivo using non-invasive techniques is critical to evaluate
      the efficacy and safety of stem cell therapies. Superparamagnetic iron oxide
      nanoparticles (SPIONs) enable cells to be tracked using magnetic resonance
      imaging (MRI), but to obtain detectable signal cells need to be labelled with a
      sufficient amount of iron oxide. For the majority of SPIONs, this can only be
      obtained with the use of transfection agents, which can adversely affect cell
      health. Here, we have synthesised a library of dextran-based polymer coated
      SPIONs with varying surface charge from -1.5 mV to +18.2 mV via a co
      precipitation approach and investigated their ability to be directly internalised
      by stem cells without the need for transfection agents. The SPIONs were
      colloidally stable in physiological solutions. The crystalline phase of the
      particles was confirmed with powder X-ray diffraction and their magnetic
      properties were characterised using SQUID magnetometry and magnetic resonance.
      Increased surface charge led to six-fold increase in uptake of particles into
      stem cells and higher MRI contrast, with negligible change in cell viability.
      Cell tracking velocimetry was shown to be a more accurate method for predicting
      MRI contrast of stem cells compared to measuring iron oxide uptake through
      conventional bulk iron quantification. 

PMID- 26222422
TI  - PLA-poloxamer/poloxamine copolymers for ligament tissue engineering: sound
      macromolecular design for degradable scaffolds and MSC differentiation.
AB  - The treatment of anterior cruciate ligament (ACL) failures remains a current
      clinical challenge. The present study aims at providing suitable degradable
      scaffolds for ligament tissue engineering. First, we focus on the design and the
      evaluation of poly(lactide)/poloxamer or poly(lactide)/poloxamine multiblock
      copolymers selected and developed to have suitable degradation and mechanical
      properties to match ACL repair. In the second part, it is shown that the
      copolymers can be processed in the form of microfibers and scaffolds consisting
      of a combination of twisted/braided fibers to further modulate the mechanical
      properties and prepare scaffold prototypes suitable for ligament application.
      Finally, after assessment of their cytocompatibility, the polymer scaffolds are
      associated with mesenchymal stem cells (MSCs). MSC differentiation toward a
      ligament fibroblast phenotype is promoted by a dual stimulation including an
      inductive culture medium and cyclic mechanical loads. RT-qPCR analyses confirm
      the potential of our scaffolds and MSCs for ACL regeneration with upregulation of
      some differentiation markers including Scleraxis, Tenascin-C and Tenomodulin. 

PMID- 26222423
TI  - Design of a reversible inversed pH-responsive caged protein.
AB  - Controlling the self-assembly behavior of caged proteins expands their potential
      applications in nanotechnology. While the structure of a caged E2 protein from
      pyruvate dehydrogenase is inert to any pH change, the incorporation of switchable
      GALA peptide that undergoes a coil-to-helix transition at acidic pH modulates its
      self-assembly property. By substituting the native alpha-helix at the C-terminus
      of the E2 protein with the GALA peptide, we report the first engineered caged
      protein with reversible inversed pH-responsive behavior. The redesigned caged E2
      protein assumes an assembly profile that is distinct from the native state; it
      disassembles at pH 7.0 and self-assembles at pH 4.0 in a reversible manner. This
      unique reversible pH trigger suggests the applicability of the self-assembly
      control on other multi-subunit macromolecules. 

PMID- 26222424
TI  - Cell response and bioactivity of titania-zirconia-zirconium titanate nanotubes
      with different nanoscale topographies fabricated in a non-aqueous electrolyte.
AB  - The morphology and the physical and chemical characteristics of four groups of
      TiO2-ZrO2-ZrTiO4 nanotubes that were fabricated via anodization in a non-aqueous
      electrolyte were investigated in order to examine their influence on the
      bioactivity of, and cell adhesion on, Ti50Zr alloy. Scanning electron microscopy
      (SEM) and 3D profilometry were used for the characterization. The in vitro cell
      responses to nanotubular surfaces with different inner diameters (Di) between 25
      and 49 nm were assessed using osteoblast cells (SaOS2). The results of the MTS
      assay indicated that the percentage of cell adhesion on the nanotubes was
      influenced by the nanoscale topographical parameters including the tube inner
      diameter (Di), the tube wall thickness (Wt), the amplitude roughness (Sa) and the
      spacing roughness (Sm) of the nanotubular surface. Cell adhesion was promoted to
      84.9% on nanotubes with an inner diameter of 25 nm, or 80.3% on nanotubes with a
      large wall thickness of 34 nm due to the accelerated integrin clustering and
      focal contacts of formation. A nanotubular surface with a low spacing roughness
      of 33 nm(3) nm(-2) led to a cell adhesion of 61.0%. Similarly, a nanotubular
      surface with a high amplitude roughness of 1.03 MUm revealed a cell adhesion of
      61.5% in instances where the inner diameters (29 nm) and wall thicknesses (24 nm)
      were within the critical dimensional parameters for cells to survive and thrive. 

PMID- 26222425
TI  - Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for
      targeted delivery of doxorubicin.
AB  - The development and evaluation of folate-targeted and reduction-triggered
      biodegradable nanoparticles are introduced to the research on targeted delivery
      of doxorubicin (DOX). This type of folate-targeted lipid-polymer hybrid
      nanoparticles (FLPNPs) is comprised of a poly(D,L-lactide-co-glycolide) (PLGA)
      core, a soybean lecithin monolayer, a monomethoxy-poly(ethylene glycol)-S-S
      hexadecyl (mPEG-S-S-C16) reduction-sensitive shell, and a folic acid-targeted
      ligand. FLPNPs exhibited high size stability but fast disassembly in a simulated
      cancer cell reductive environment. The experiments on the release process in
      vitro revealed that as a reduction-sensitive drug delivery system, FLPNPs
      released DOX faster in the presence of 10 mM dithiothreitol (DTT). Results from
      flow cytometry, confocal image and in vitro cytotoxicity assays revealed that
      FLPNPs further enhanced cell uptake and generated higher cytotoxicity against
      human epidermoid carcinoma in the oral cavity than non-targeted redox-sensitive
      and targeted redox-insensitive controls. Furthermore, in vivo animal experiments
      demonstrated that systemic administration of DOX-loaded FLPNPs remarkably reduced
      tumor growth. Experiments on biodistribution of DOX-loaded FLPNPs showed that an
      increasing amount of DOX accumulated in the tumor. Therefore, FLPNPs formulations
      have proved to be a stable, controllable and targeted anticancer drug delivery
      system.

PMID- 26222426
TI  - The bifunctional regulation of interconnected Zn-incorporated ZrO2 nanoarrays in
      antibiosis and osteogenesis.
AB  - New generation biomaterials should be designed to bear long-term antibacterial
      activity, biocompatibility and even osteogenesis facilitation. In this study, the
      bifunctional regulation of antibiosis and osteogenesis is realized by the highly
      ordered and interconnecting Zn-incorporated ZrO2 nanoarrays, which are prepared
      by a hydrothermal approach with the precursor hydrolyzed in situ and allow long
      term controllable Zn release. The content of incorporated Zn can be easily
      controlled by pH of the HCl solution used for etching. All Zn-incorporated
      nanoarrays show good antibacterial properties against both Escherichia coli (E.
      coli, Gram-negative) and Staphylococcus aureus (S. aureus, Gram-positive), as
      indicated by high antibacterial rates and the apparent inhibition zone. Analysis
      of the biocompatibility confirms that the hybrid nanoarrays could cause varying
      degrees of promotion for the adhesion and spreading of MC3T3-E1 cells. Zn
      incorporated ZrO2 nanotubes balance antibiosis and osteogenesis delicately, as
      proved by the up-regulated MTT and ALP activities, as well as the increase of
      bone-related gene expression (the mRNA level of OCN, OPN and BMP-2). The novel
      bone implant materials with better antibacterial properties can promote the
      osteogenesis, and have promising applications in biomedical devices and
      antibacterial control systems. 

PMID- 26222428
TI  - Unilateral Stellate Purpura of the Ankle. Septic emboli.

PMID- 26222427
TI  - Chemical Characterization of N-Linked Oligosaccharide As the Antigen Epitope
      Recognized by an Anti-Sperm Auto-Monoclonal Antibody, Ts4.
AB  - Ts4, an anti-sperm auto-monoclonal antibody, possesses immunoreactivity to the
      acrosomal region of mouse epididymal spermatozoa. In addition, the mAb shows
      specific immunoreactivity to reproduction-related regions such as testicular germ
      cells and early embryo. Our qualitative study previously showed that the antigen
      epitope for Ts4 contained a N-linked common oligosaccharide (OS) chain on
      testicular glycoproteins as determined by Western blotting for testicular
      glycoproteins after treatment with several glycohydrolases. Since the
      distribution of the Ts4-epitope is unique, the OS chain in Ts4-epitope may have
      role(s) in the reproductive process. The aim of this study was to clarify the
      molecular structure of the Ts4-epitope, particularly its OS moiety. Using Ts4
      immunoprecipitation combined with liquid chromatography and multiple-stage mass
      spectrometry, the candidate carbohydrate structure in the Ts4-epitope is proposed
      to be N-linked fucosylated agalacto-biantennary with bisecting N
      acetylglucosamine (GlcNAc) or with N-acetylgalactosamine-GlcNAc motif. Further
      binding analyses using various lectins against the mouse testicular Ts4
      immunoprecipitants revealed that Phaseolus vulgaris erythroagglutinin and Pisum
      sativum agglutinin showed positive staining of the bands corresponding to Ts4
      reactive proteins. Moreover, the immunoreactivity of Ts4 against the testicular
      extract was completely abrogated after digestion with beta-N
      acetylglucosaminidase. These results show that the Ts4-epitope contains agalacto
      biantennary N-glycan with bisecting GlcNAc carrying fucose residues. 

PMID- 26222429
TI  - A Comprehensive Analysis of the Transcriptomes of Marssonina brunnea and Infected
      Poplar Leaves to Capture Vital Events in Host-Pathogen Interactions.
AB  - BACKGROUND: Understanding host-pathogen interaction mechanisms helps to elucidate
      the entire infection process and focus on important events, and it is a promising
      approach for improvement of disease control and selection of treatment strategy.
      Time-course host-pathogen transcriptome analyses and network inference have been
      applied to unravel the direct or indirect relationships of gene expression
      alterations. However, time series analyses can suffer from absent time points due
      to technical problems such as RNA degradation, which limits the application of
      algorithms that require strict sequential sampling. Here, we introduce an
      efficient method using independence test to infer an independent network that is
      exclusively concerned with the frequency of gene expression changes. RESULTS:
      Highly resistant NL895 poplar leaves and weakly resistant NL214 leaves were
      infected with highly active and weakly active Marssonina brunnea, respectively,
      and were harvested at different time points. The independent network inference
      illustrated the top 1,000 vital fungus-poplar relationships, which contained 768
      fungal genes and 54 poplar genes. These genes could be classified into three
      categories: a fungal gene surrounded by many poplar genes; a poplar gene
      connected to many fungal genes; and other genes (possessing low degrees of
      connectivity). Notably, the fungal gene M6_08342 (a metalloprotease) was
      connected to 10 poplar genes, particularly including two disease-resistance
      genes. These core genes, which are surrounded by other genes, may be of
      particular importance in complicated infection processes and worthy of further
      investigation. CONCLUSIONS: We provide a clear framework of the interaction
      network and identify a number of candidate key effectors in this process, which
      might assist in functional tests, resistant clone selection, and disease control
      in the future.

PMID- 26222430
TI  - Gait Pattern Alterations during Walking, Texting and Walking and Texting during
      Cognitively Distractive Tasks while Negotiating Common Pedestrian Obstacles.
AB  - OBJECTIVES: Mobile phone texting is a common daily occurrence with a paucity of
      research examining corresponding gait characteristics. To date, most studies have
      participants walk in a straight line vs. overcoming barriers and obstacles that
      occur during regular walking. The aim of our study is to examine the effect of
      mobile phone texting during periods of cognitive distraction while walking and
      negotiating barriers synonymous with pedestrian traffic. METHODS: Thirty
      participants (18-50 y) completed three randomized, counter-balanced walking tasks
      over a course during: (1) normal walking (control), (2) texting and walking, and
      (3) texting and walking whilst being cognitively distraction via a standard
      mathematical test performed while negotiating the obstacle course. We analyzed
      gait characteristics during course negotiation using a 3-dimensional motion
      analysis system and a general linear model and Dunnet-Hsu post-hoc procedure the
      normal walking condition to assess gait characteristic differences. Primary
      outcomes included the overall time to complete the course time and barrier
      contact. Secondary outcomes included obstacle clearance height, step frequency,
      step time, double support phase and lateral deviation. RESULTS: Participants took
      significantly longer (mean +/- SD) to complete the course while texting (24.96 +/
      4.20 sec) and during cognitive distraction COG (24.09 +/- 3.36 sec) vs. normal
      walking (19.32 +/- 2.28 sec; all, P<0.001). No significant differences were noted
      for barrier contacts (P = 0.28). Step frequency, step time, double support phase
      and lateral deviation all increased in duration during the texting and cognitive
      distraction trial. Texting and being cognitively distracted also increased
      obstacle clearance versus the walking condition (all, P<0.02). CONCLUSIONS:
      Texting while walking and/or being cognitively distracted significantly affect
      gait characteristics concordant to mobile phone usage resulting in a more
      cautious gate pattern. Future research should also examine a similar study in
      older participants who may be at a greater risk of tripping with such walking
      deviations.

PMID- 26222431
TI  - Experimental Evaluation of the Heat Sink Effect in Hepatic Microwave Ablation.
AB  - PURPOSE: To demonstrate and quantify the heat sink effect in hepatic microwave
      ablation (MWA) in a standardized ex vivo model, and to analyze the influence of
      vessel distance and blood flow on lesion volume and shape. MATERIALS AND METHODS:
      108 ex vivo MWA procedures were performed in freshly harvested pig livers.
      Antennas were inserted parallel to non-perfused and perfused (700,1400 ml/min)
      glass tubes (diameter 5mm) at different distances (10, 15, 20mm). Ablation zones
      (radius, area) were analyzed and compared (Kruskal-Wallis Test, Dunn's multiple
      comparison Test). Temperature changes adjacent to the tubes were measured
      throughout the ablation cycle. RESULTS: Maximum temperature decreased
      significantly with increasing flow and distance (p<0.05). Compared to non
      perfused tubes, ablation zones were significantly deformed by perfused tubes
      within 15 mm distance to the antenna (p<0.05). At a flow rate of 700 ml/min
      ablation zone radius was reduced to 37.2% and 80.1% at 10 and 15 mm tube
      distance, respectively; ablation zone area was reduced to 50.5% and 89.7%,
      respectively. CONCLUSION: Significant changes of ablation zones were demonstrated
      in a pig liver model. Considerable heat sink effect was observed within a
      diameter of 15 mm around simulated vessels, dependent on flow rate. This has to
      be taken into account when ablating liver lesions close to vessels.

PMID- 26222432
TI  - Inclined angle-controlled growth of GaN nanorods on m-sapphire by metal organic
      chemical vapor deposition without a catalyst.
AB  - In this study, we have intentionally grown novel types of (11-22)- and (1-10-3)
      oriented(3) and self-assembled inclined GaN nanorods (NRs) on (10-10) m-sapphire
      substrates using metal organic chemical vapor deposition without catalysts and ex
      situ patterning. Nitridation of the m-sapphire surface was observed to be crucial
      to the inclined angle as well as the growth direction of the GaN NRs. Polarity
      selective KOH etching confirmed that both (11-22) and (1-10-3) GaN NRs are
      nitrogen-polar. Using pole figure measurements and selective area electron
      diffraction patterns, the epitaxial relationship between the inclined (11-22) and
      (1-10-3) GaN NRs and m-sapphire substrates was systematically demonstrated.
      Furthermore, it was verified that the GaN NRs were single-crystalline wurtzite
      structures. We observed that stacking fault-related defects were generated during
      the initial growth stage using high-resolution transmission electron microscopy.
      The blue-shift of the near band edge (NBE) peak in the inclined angle-controlled
      GaN NRs can be explained by a band filling effect through carrier saturation of
      the conduction band, resulting from a high Si-doping concentration; in addition,
      the decay time of NBE emission in (11-22)- and (1-10-3)-oriented NRs was much
      shorter than that of stacking fault-related emission. These results suggest that
      defect-free inclined GaN NRs can be grown on m-sapphire without ex situ
      treatment. 

PMID- 26222434
TI  - Correction: Ecological Diversity in South American Mammals: Their Geographical
      Distribution Shows Variable Associations with Phylogenetic Diversity and Does Not
      Follow the Latitudinal Richness Gradient.

PMID- 26222433
TI  - Role of TrkB during the postnatal development of the rat carotid body.
AB  - Brain-derived neurotrophic factor (BDNF) supports innervation of the carotid body
      by neurons projecting from the petrosal ganglion. Although carotid body glomus
      cells also express TrkB, BDNF's high affinity receptor, the role of BDNF in
      carotid body growth and O2 sensitivity has not been studied. Neonatal rats were
      treated with the TrkB antagonist K252a (100 MUg kg(-1), i.p., b.i.d.) or vehicle
      on postnatal days P0-P6 and studied on P7. Carotid body volume was decreased by
      35% after chronic K252a (P<0.001); a reduction in carotid body size was also
      elicited using the more selective TrkB antagonist ANA-12 (500 MUg kg(-1), i.p.,
      b.i.d.). In contrast, single-unit chemoafferent responses to 5% O2, measured in
      vitro, were unaffected by chronic K252a administration. Normoxic and hypoxic
      ventilation, measured by head-body plethysmography, were also normal after
      chronic K252a administration, but acute K252a administration produced a slower,
      deeper breathing pattern during the transition into hypoxia. These data suggest
      that BDNF regulates postnatal carotid body growth but does not influence the
      development of glomus cell O2 sensitivity.

PMID- 26222435
TI  - Crinone Gel for Luteal Phase Support in Frozen-Thawed Embryo Transfer Cycles: A
      Prospective Randomized Clinical Trial in the Chinese Population.
AB  - To compare Crinone vaginal progesterone gel with intramuscularly injected
      progesterone for luteal phase support in progesterone-supplemented frozen-thawed
      embryo transfer (FET) cycles, a randomized prospective study of patients
      qualified for FET was conducted between September 2010 and January 2013 at a
      hospital in Shanghai, China. From the day of transformation into secretory phase
      endometrium (day 0), Crinone vaginal gel (90 mg/d) was administered to patients
      in the Gel Group, while progesterone (40 mg/d) was injected intramuscularly in
      patients in the Inj Group (n = 750 per group). All patients received oral
      dydrogesterone (20 mg/d) and estradiol valerate (4-8 mg/d). Day 3 embryos with
      the highest pre-frozen scores were transferred to patients in the two groups and
      the clinical outcomes compared. This study comprised 1,500 cycles (750 in each
      group). Twenty-nine cycles in the Gel Group and 24 in the Inj Group were
      withdrawn. There were no significant differences between groups in age,
      endometrial thickness, endometrial preparation time or number of embryos
      transferred. No significant differences were observed between the Gel Group and
      Inj Group in the rates of live birth (32.6% vs. 31.7%, P = 0.71), clinical
      pregnancy (40.1% vs. 40.6%, P = 0.831), implantation (25.8% vs. 25.3%, P =
      0.772), abortion (16.3% vs. 18.3%, P = 0.514) or ectopic pregnancy (2.8% vs.
      4.4%, P = 0.288). Multivariate logistic regression analysis revealed that the
      odds ratios (95% confidence intervals) for the rates of live birth, clinical
      pregnancy, abortion and ectopic pregnancy (Gel Group relative to Inj Group) were
      1.036 (0.829-1.295), 0.971 (0.785-1.200), 0.919 (0.595-1.420) and 0.649 (0.261
      1.614), respectively. Our study revealed that using Crinone vaginal gel in FET
      cycles achieved similar pregnancy outcomes to intramuscular progesterone,
      indicating that vaginal gel is a viable alternative to intramuscular injection.
      TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-14004565.

PMID- 26222437
TI  - Friendly Skulls, Mechanical Bodies: Encounters with Cadavers in a Medical School
      in Egypt.
AB  - Anatomy and cadavers trigger fear and produce contradictory responses. In these
      circumstances, allegedly Western models of learning and the exposure to death
      have to be appropriated to become viable. Furthermore, references to the
      religious and cultural backgrounds of students shape their responses. According
      to students, death is an event when the deceased acquires supernatural powers;
      thus, they take shield in religion to ward off potential dangers caused by
      spirits. The exposure to the interior of the body also produces heightened
      feelings of religiosity and perceiving the body as a miracle. Befriending skulls
      and body parts and giving them names are strategies to humanize dead bodies and
      render them familiar. However, in order to legitimize working with cadavers and
      the dissection of bodies, students tend to dehumanize cadavers and observe them
      as mechanical objects. 

PMID- 26222436
TI  - Redundant Roles of Rpn10 and Rpn13 in Recognition of Ubiquitinated Proteins and
      Cellular Homeostasis.
AB  - Intracellular proteins tagged with ubiquitin chains are targeted to the 26S
      proteasome for degradation. The two subunits, Rpn10 and Rpn13, function as
      ubiquitin receptors of the proteasome. However, differences in roles between
      Rpn10 and Rpn13 in mammals remains to be understood. We analyzed mice deficient
      for Rpn13 and Rpn10. Liver-specific deletion of either Rpn10 or Rpn13 showed only
      modest impairment, but simultaneous loss of both caused severe liver injury
      accompanied by massive accumulation of ubiquitin conjugates, which was recovered
      by re-expression of either Rpn10 or Rpn13. We also found that mHR23B and
      ubiquilin/Plic-1 and -4 failed to bind to the proteasome in the absence of both
      Rpn10 and Rpn13, suggesting that these two subunits are the main receptors for
      these UBL-UBA proteins that deliver ubiquitinated proteins to the proteasome. Our
      results indicate that Rpn13 mostly plays a redundant role with Rpn10 in
      recognition of ubiquitinated proteins and maintaining homeostasis in Mus
      musculus. 

PMID- 26222438
TI  - Pharmacophore model prediction, 3D-QSAR and molecular docking studies on vinyl
      sulfones targeting Nrf2-mediated gene transcription intended for anti-Parkinson
      drug design.
AB  - Despite intense research efforts towards clinical and molecular causes of
      Parkinson disease (PD), the etiology of disease still remains unclear. However,
      recent studies have provided ample evidences that the oxidative stress is the key
      player that contributes a lot to dopaminergic (DAergic) neurodegeneration in
      brain. It is due to the discrepancy of antioxidant defence system of which
      nuclear factor erythroid 2-related factor 2 (Nrf2) signalling is of central
      contour. In the current study, potent heme oxygenase-1 agonists (Nrf2 signalling
      regulator), vinyl sulfones, were selected and an optimal pharmacophore model was
      brought forth which was examined using a decoy set by atom-based 3D-QSAR. The
      best four-feature model consists of two hydrogen bond acceptors and two aromatic
      rings, which has the highest correlation coefficient, R(2) = .71 and [Formula:
      see text] = .73 in QSAR. These ligands were further studied for molecular docking
      with Nrf2-keap protein to gain insight into the major binding motifs followed by
      analysing pharmacokinetic properties to evaluate their bioavailability dominance.
      From this study, it is concluded that vinyl sulfones could be ideal compounds for
      targeting Nrf2 pathway which in turn halt the PD progression. Hence, these can be
      considered as potential leads for drug development against the same. 

PMID- 26222440
TI  - Fluorescence Polarization Screening Assays for Small Molecule Allosteric
      Modulators of ABL Kinase Function.
AB  - The ABL protein-tyrosine kinase regulates intracellular signaling pathways
      controlling diverse cellular processes and contributes to several forms of
      cancer. The kinase activity of ABL is repressed by intramolecular interactions
      involving its regulatory Ncap, SH3 and SH2 domains. Small molecules that
      allosterically regulate ABL kinase activity through its non-catalytic domains may
      represent selective probes of ABL function. Here we report a screening assay for
      chemical modulators of ABL kinase activity that target the regulatory interaction
      of the SH3 domain with the SH2-kinase linker. This fluorescence polarization (FP)
      assay is based on a purified recombinant ABL protein consisting of the N-cap, SH3
      and SH2 domains plus the SH2-kinase linker (N32L protein) and a short fluorescein
      labeled probe peptide that binds to the SH3 domain. In assay development
      experiments, we found that the probe peptide binds to the recombinant ABL N32L
      protein in vitro, producing a robust FP signal that can be competed with an
      excess of unlabeled peptide. The FP signal is not observed with control N32L
      proteins bearing either an inactivating mutation in the SH3 domain or enhanced
      SH3:linker interaction. A pilot screen of 1200 FDA-approved drugs identified four
      compounds that specifically reduced the FP signal by at least three standard
      deviations from the untreated controls. Secondary assays showed that one of these
      hit compounds, the antithrombotic drug dipyridamole, enhances ABL kinase activity
      in vitro to a greater extent than the previously described ABL agonist, DPH.
      Docking studies predicted that this compound binds to a pocket formed at the
      interface of the SH3 domain and the linker, suggesting that it activates ABL by
      disrupting this regulatory interaction. These results show that screening assays
      based on the non-catalytic domains of ABL can identify allosteric small molecule
      regulators of kinase function, providing a new approach to selective drug
      discovery for this important kinase system. 

PMID- 26222441
TI  - Experience with Subgam, a Subcutaneously Administered Human Normal Immunoglobulin
      (ClinicalTrials.gov--NCT02247141).
AB  - BACKGROUND AND OBJECTIVES: A multi-centre, non-comparative study examining the
      efficacy and safety of Subgam, a normal immunoglobulin (IgG) given weekly as a
      rapid subcutaneous infusion to patients with primary immune deficiency (PID), is
      reported. Also included is a summary of adverse drug reactions associated with
      the use of marketed Subgam in the UK. MATERIALS AND METHODS: 50 patients with
      stable PID on IgG therapy were enrolled: Stage 1 included three infusions with
      prior IgG product followed by 6 months with Subgam, Stage 2 involved long-term
      Subgam therapy up to 4 years. RESULTS: Stage 1, 85% of the subjects aged >12
      years and 93% of the subjects aged <12 years achieved IgG levels >=6 and >=4 g/L,
      respectively at all observations. There were 3.62 infections/patient/year during
      Subgam treatment. The most common product-related events were infusion site
      reactions (50% of patients). Recent post-hoc pharmacokinetics analysis of the
      post-infusion serum total IgG concentration indicated that the mean dose
      normalised incremental IgG AUCtau following intravenous dosing (120.5 g.day/L)
      was 1.64-fold that of the dose-normalised mean incremental IgG AUCtau following
      subcutaneous dosing (73.6 g.day/L), corresponding to an estimated IgG
      bioavailability for subcutaneous dosing of 61%. Only 34 post-licensing adverse
      reactions have been received in 30 patients over a period of 10 years; fourteen
      were classed as serious as defined by the ICH guidelines on good clinical
      practice. The most common post-licensing adverse reaction was infusion site
      reaction (7 reports). There were 7 reports of flu-like symptoms
      (pyrexia/shivering/rigors/feeling hot or cold), 2 other reports of combined flu
      like symptoms and infusion site reactions, 5 reports of generalised skin
      reactions, and 3 reports of combined infusion site and skin reactions. There were
      also reports of anaphylaxis (2 reports) and 8 other adverse events (including
      headache). In conclusion, Subgam is effective and well tolerated in the treatment
      of PID. TRIAL REGISTRATION: ClinicalTrials.gov NCT02247141.

PMID- 26222439
TI  - Substrate Specificity, Inhibitor Selectivity and Structure-Function Relationships
      of Aldo-Keto Reductase 1B15: A Novel Human Retinaldehyde Reductase.
AB  - Human aldo-keto reductase 1B15 (AKR1B15) is a newly discovered enzyme which
      shares 92% amino acid sequence identity with AKR1B10. While AKR1B10 is a well
      characterized enzyme with high retinaldehyde reductase activity, involved in the
      development of several cancer types, the enzymatic activity and physiological
      role of AKR1B15 are still poorly known. Here, the purified recombinant enzyme has
      been subjected to substrate specificity characterization, kinetic analysis and
      inhibitor screening, combined with structural modeling. AKR1B15 is active towards
      a variety of carbonyl substrates, including retinoids, with lower kcat and Km
      values than AKR1B10. In contrast to AKR1B10, which strongly prefers all-trans
      retinaldehyde, AKR1B15 exhibits superior catalytic efficiency with 9-cis
      retinaldehyde, the best substrate found for this enzyme. With ketone and
      dicarbonyl substrates, AKR1B15 also shows higher catalytic activity than AKR1B10.
      Several typical AKR inhibitors do not significantly affect AKR1B15 activity.
      Amino acid substitutions clustered in loops A and C result in a smaller, more
      hydrophobic and more rigid active site in AKR1B15 compared with the AKR1B10
      pocket, consistent with distinct substrate specificity and narrower inhibitor
      selectivity for AKR1B15.

PMID- 26222443
TI  - Targeting Accuracy, Procedure Times and User Experience of 240 Experimental MRI
      Biopsies Guided by a Clinical Add-On Navigation System.
AB  - OBJECTIVES: MRI is of great clinical utility for the guidance of special
      diagnostic and therapeutic interventions. The majority of such procedures are
      performed iteratively ("in-and-out") in standard, closed-bore MRI systems with
      control imaging inside the bore and needle adjustments outside the bore. The
      fundamental limitations of such an approach have led to the development of
      various assistance techniques, from simple guidance tools to advanced navigation
      systems. The purpose of this work was to thoroughly assess the targeting
      accuracy, workflow and usability of a clinical add-on navigation solution on 240
      simulated biopsies by different medical operators. METHODS: Navigation relied on
      a virtual 3D MRI scene with real-time overlay of the optically tracked biopsy
      needle. Smart reference markers on a freely adjustable arm ensured proper
      registration. Twenty-four operators - attending (AR) and resident radiologists
      (RR) as well as medical students (MS) - performed well-controlled biopsies of 10
      embedded model targets (mean diameter: 8.5 mm, insertion depths: 17-76 mm).
      Targeting accuracy, procedure times and 13 Likert scores on system performance
      were determined (strong agreement: 5.0). RESULTS: Differences in diagnostic
      success rates (AR: 93%, RR: 88%, MS: 81%) were not significant. In contrast,
      between-group differences in biopsy times (AR: 4:15, RR: 4:40, MS: 5:06 min:sec)
      differed significantly (p<0.01). Mean overall rating was 4.2. The average
      operator would use the system again (4.8) and stated that the outcome justifies
      the extra effort (4.4). Lowest agreement was reported for the robustness against
      external perturbations (2.8). CONCLUSIONS: The described combination of optical
      tracking technology with an automatic MRI registration appears to be sufficiently
      accurate for instrument guidance in a standard (closed-bore) MRI environment.
      High targeting accuracy and usability was demonstrated on a relatively large
      number of procedures and operators. Between groups with different expertise there
      were significant differences in experimental procedure times but not in the
      number of successful biopsies.

PMID- 26222442
TI  - High-Frequency Stimulation of the Rat Entopeduncular Nucleus Does Not Provide
      Functional or Morphological Neuroprotection from 6-Hydroxydopamine.
AB  - Deep brain stimulation (DBS) is the most common neurosurgical treatment for
      Parkinson's disease (PD). Whereas the globus pallidus interna (GPi) has been less
      commonly targeted than the subthalamic nucleus (STN), a recent clinical trial
      suggests that GPi DBS may provide better outcomes for patients with psychiatric
      comorbidities. Several laboratories have demonstrated that DBS of the STN
      provides neuroprotection of substantia nigra pars compacta (SNpc) dopamine
      neurons in preclinical neurotoxin models of PD and increases brain-derived
      neurotrophic factor (BDNF). However, whether DBS of the entopeduncular nucleus
      (EP), the homologous structure to the GPi in the rat, has similar neuroprotective
      potential in preclinical models has not been investigated. We investigated the
      impact of EP DBS on forelimb use asymmetry and SNpc degeneration induced by 6
      hydroxydopamine (6-OHDA) and on BDNF levels. EP DBS in male rats received
      unilateral, intrastriatal 6-OHDA and ACTIVE or INACTIVE stimulation continuously
      for two weeks. Outcome measures included quantification of contralateral forelimb
      use, stereological assessment of SNpc neurons and BDNF levels. EP DBS 1) did not
      ameliorate forelimb impairments induced by 6-OHDA, 2) did not provide
      neuroprotection for SNpc neurons and 3) did not significantly increase BDNF
      levels in any of the structures examined. These results are in sharp contrast to
      the functional improvement, neuroprotection and BDNF-enhancing effects of STN DBS
      under identical experimental parameters in the rat. The lack of functional
      response to EP DBS suggests that stimulation of the rat EP may not represent an
      accurate model of clinical GPi stimulation. 

PMID- 26222446
TI  - A techno-economic model of a solid oxide electrolysis system.
AB  - Solid oxide cells can play a vital role in addressing energy and environmental
      issues. In fuel cell mode they are capable of producing electric energy at high
      efficiency using hydrocarbon fuels and in the electrolysis mode can produce
      hydrogen from steam or synthesis gas from a mixture of steam and carbon dioxide.
      The solid oxide electrolysis cells (SOECs) can operate at a wide range of
      conditions. A capable means by which to select operating conditions in the
      application of solid oxide electrolyzers is a necessity for successful commercial
      operation. Power and efficiency can be determined over a wide range of operating
      conditions by applying fundamental electrochemical principles to a SOEC system.
      Operating conditions may be selected based on power requirements or with
      efficiency as a priority. Operating cost for electricity which is a function of
      both power and efficiency can also be used to determine optimal operating
      conditions. Performance maps based on closed form isothermal parametric models
      for both hydrogen and natural gas fueled SOFC stacks have been demonstrated
      previously. This approach applied to a SOEC stack is shown. This model was
      applied to generate performance maps for a solid oxide cell stack operated in the
      electrolysis mode. The functional form of the model and the boundaries of the
      operating envelope provide useful insight into the SOEC operating characteristics
      and a simple means of selecting conditions for electrolysis operation. 

PMID- 26222445
TI  - Carbamoyl Triazoles, Known Serine Protease Inhibitors, Are a Potent New Class of
      Antimalarials.
AB  - Screening of the GSK corporate collection, some 1.9 million compounds, against
      Plasmodium falciparum (Pf), revealed almost 14000 active hits that are now known
      as the Tres Cantos Antimalarial Set (TCAMS). Followup work by Calderon et al.
      clustered and computationally filtered the TCAMS through a variety of criteria
      and reported 47 series containing a total of 522 compounds. From this enhanced
      set, we identified the carbamoyl triazole TCMDC-134379 (1), a known serine
      protease inhibitor, as an excellent starting point for SAR profiling. Lead
      optimization of 1 led to several molecules with improved antimalarial potency,
      metabolic stabilities in mouse and human liver microsomes, along with acceptable
      cytotoxicity profiles. Analogue 44 displayed potent in vitro activity (IC50 = 10
      nM) and oral activity in a SCID mouse model of Pf infection with an ED50 of 100
      and ED90 of between 100 and 150 mg kg(-1), respectively. The results presented
      encourage further investigations to identify the target of these highly active
      compounds. 

PMID- 26222444
TI  - Gene regulation by dietary microRNAs.
AB  - MicroRNAs (miRNAs) silence genes through destabilizing mRNA or preventing
      translation of mRNA, thereby playing an essential role in gene silencing.
      Traditionally, miRNAs have been considered endogenous regulators of genes, i.e.,
      miRNAs synthesized by an organism regulate the genes in that organism. Recently,
      that dogma has been challenged in studies suggesting that food-borne miRNAs are
      bioavailable and affect gene expression in mice and humans. While the evidence in
      support of this theory may be considered weak for miRNAs that originate in
      plants, there is compelling evidence to suggest that humans use bovine miRNAs in
      cow's milk and avian miRNAs in chicken eggs for gene regulation. Importantly,
      evidence also suggests that mice fed a miRNA-depleted diet cannot compensate for
      dietary depletion by increased endogenous synthesis. Bioinformatics predictions
      implicate bovine miRNAs in the regulation of genes that play roles in human
      health and development. Current challenges in this area of research include that
      some miRNAs are unable to establish a cause-and-effect between miRNA depletion
      and disease in miRNA knockout mice, and sequence similarities and identities for
      bovine and human miRNAs render it difficult to distinguish between exogenous and
      endogenous miRNAs. Based on what is currently known about dietary miRNAs, the
      body of evidence appears to be sufficient to consider milk miRNA bioactive
      compounds in foods, and to increase research activities in this field. 

PMID- 26222447
TI  - An Open-Label, Randomized Trial of Methylphenidate and Atomoxetine Treatment in
      Children with Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: The efficacy of both methylphenidate and atomoxetine has been
      established in placebo-controlled trials. The present study aimed to directly
      compare the efficacy of methylphenidate and atomoxetine in improving symptoms
      among children with attention-deficit/hyperactivity disorder (ADHD). METHODS: The
      study sample included 160 drug-naive children and adolescents 7-16 years of age,
      with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system
      methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24
      week, open-label, head-to-head clinical trial. The primary efficacy measure was
      the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered
      and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical
      Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and
      Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents,
      teachers, and subjects. RESULTS: At week 24, mean changes in ADHD-RS-IV
      Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate
      and 12.65 points (Cohen's d, -3.05) for atomoxetine; and mean changes in ADHD-RS
      IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS
      methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of
      parent-, teacher-, and self-ratings on behavioral symptoms, both of the two
      treatment groups significantly decreased on the SNAP-IV scores at the end-point,
      with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from
      0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate;
      and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the
      Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant
      differences between treatment groups were observed on the outcome measures.
      Vomiting, somnolence, and dizziness were reported more often for atomoxetine than
      for OROS-methylphenidate, whereas insomnia was reported more often for OROS
      methylphenidate than for atomoxetine. CONCLUSIONS: After 24 weeks of treatment,
      OROS-methylphenidate and atomoxetine had comparable efficacy in reducing core
      ADHD symptoms in drug-naive children and adolescents with ADHD.

PMID- 26222448
TI  - Suicide and Other-Cause Mortality after Early Exposure to Smoking and Second Hand
      Smoking: A 12-Year Population-Based Follow-Up Study.
AB  - BACKGROUND: The association between smoking and suicide is still controversial,
      particular for early life cigarette smoking exposure. Few studies have
      investigated this association in adolescents using population-based cohorts, and
      the relationship with second hand smoking (SHS) exposure has not been addressed.
      METHODS AND FINDINGS: In this study, we followed a large population-based sample
      of younger people to investigate the association between smoking, SHS exposure
      and suicide mortality. Between October 1995 and June 1996, 162,682 junior high
      school students ages 11 to 16 years old living in a geographic catchment area in
      Taiwan were enrolled and then followed till December 2007 (1,948,432 person
      years) through linkage to the National Death Certification System. Participants
      who were currently smoking at baseline had a greater than six-fold higher suicide
      mortality than those who did not smoke (29.5 vs. 4.8 per 100,000 person-years,
      p<0.001) as well as higher natural mortality (33.7 vs. 10.3 per 100,000 person
      years, p<0.001). After controlling for gender, age, parental education, asthma,
      allergic rhinitis, and alcohol consumption, the adjusted hazard ratios for
      suicide were 3.69 (95% CI 1.85-7.39) in current smokers, and 1.47 (95% CI 0.94
      2.30) and 2.83 (95% CI 1.54-5.20) respectively in adolescents exposed to SHS of 1
      20 cigarettes and >20 cigarettes/per day. The estimated depression-adjusted odds
      ratio did not change substantially. The population attributable fractions for
      suicide associated with smoking and heavy SHS exposure (>20 cigarettes/per day)
      were 9.6% and 10.6%, respectively. CONCLUSIONS: This study showed evidence of
      excess suicide mortality among young adults exposed to active or passive early
      life cigarette smoking.

PMID- 26222449
TI  - Design, synthesis and anticancer activity of Michael-type thiol adducts of alpha
      santonin analogue with exocyclic methylene.
AB  - A series of Michael-type analogues were generated on the C-ring of alpha-santonin
      (alpha-methylene-gamma-butyrolactone) upon reaction with various thiols. All the
      thiol adducts synthesized were evaluated for their anticancer activity against
      four human cancer cell lines (PC-3, HCT-15, A-549 and MCF-7). Bioassay results
      indicated that even though most of the synthesized compounds exhibited a good
      anticancer activity against various cancer cells in vitro, some of the compounds
      like 9e, 9g and 9q were found to be the most promising analogues in this series,
      with compound 9e showing IC50 values of 1.5 MUM, 0.6 MUM, 2.4 MUM and 1.2 MUM on
      PC-3, MCF-7, A-549 and HCT-116 cell lines respectively. Further, flow cytometry
      studies showed that MCF-7 cells treated with the compounds 9e, 9g and 9q were
      arrested in the sub G1 phase of the cell cycle in a concentration dependent
      manner. These lead molecules were further studied for NF-kappaB, p65
      transcription factor inhibitory activity which confirmed concentration dependent
      inhibition against NF-kappaB, p65 with analogue 9e showing 57% inhibition at 2
      MUM, 9g showing 62% inhibition at 3 MUM and 9q showing 54% inhibition at 2 MUM
      concentration. 

PMID- 26222450
TI  - Revisiting Patient Satisfaction Surveys.

PMID- 26222451
TI  - Vaccine Fear Derails Triumph Over Disease.

PMID- 26222453
TI  - A Diverse Workforce.

PMID- 26222454
TI  - A Diverse Workforce.

PMID- 26222455
TI  - Mindfulness.

PMID- 26222456
TI  - Workplace Conflict.

PMID- 26222457
TI  - What's Old Is New Again: Stats on Older Americans.

PMID- 26222459
TI  - In a U-Turn, the ANA Supports the National Nurse Act.

PMID- 26222460
TI  - U.S. Teens Are Smoking Less.

PMID- 26222462
TI  - Women's Health: Progress amid Setbacks.

PMID- 26222464
TI  - Fetal Demise: Caring for the Parents.

PMID- 26222470
TI  - Misplacements of Enteral Feeding Tubes Increase After Hospitals Switch Brands.
AB  - The Pennsylvania Patient Safety Reporting System is a confidential, statewide
      Internet reporting system to which all Pennsylvania hospitals, outpatient-surgery
      facilities, birthing centers, and abortion facilities must file information on
      incidents and serious events. Safety Monitor is a column from Pennsylvania's
      Patient Safety Authority, the authority that informs nurses on issues that can
      affect patient safety and presents strategies they can easily integrate into
      practice. For more information on the authority, visit
      www.patientsafetyauthority.org. For the original article discussed in this column
      or for other articles on patient safety, click on "Patient Safety Advisories" and
      then "Advisory Library" in the left-hand navigation menu.

PMID- 26222473
TI  - The Evolution of Physical Activity Promotion.
AB  - A physically active lifestyle has numerous physical and mental health benefits
      for patients of all ages. Despite these significant benefits, a majority of
      Americans do not meet current physical activity guidelines. Health care
      providers, especially nurses, play a vital role in physical activity promotion.
      Over the past several decades, exercise and physical activity guidelines have
      evolved from a focus on structured, vigorous exercise to a focus on moderate
      intensity "lifestyle" physical activity. The author updates nurses on physical
      activity guidelines and provides tips for promoting physical activity, with a
      focus on lifestyle activities such as walking to work. This article also
      addresses new research findings on the importance of decreasing sedentary and
      sitting time, even in physically active people.

PMID- 26222474
TI  - Vaccine Safety Resources for Nurses.

PMID- 26222477
TI  - Conflict Engagement: Emotional and Social Intelligence.
AB  - This article is one in a series on conflict. It is part of an ongoing series on
      leadership coordinated by the American Organization of Nurse Executives (AONE;
      www.aone.org), highlighting topics of interest to nurse managers and emerging
      nurse leaders. The AONE provides leadership, professional development, advocacy,
      and research to advance nursing practice and patient care, promote nursing
      leadership excellence, and shape public policy for health care. 

PMID- 26222478
TI  - Everyday Advocates: Nursing Advocacy Is a Full-Time Job.

PMID- 26222479
TI  - The Present.

PMID- 26222480
TI  - A Polymer-Brush-Based Nanovalve Controlled by Nanoparticle Additives: Design
      Principles.
AB  - Polymer-grafted surfaces and channels are increasingly used for the design of
      responsive materials and sensors due to robust performance and ease of use.
      Various strategies for the control of the nanoscale morphologies of such
      materials and devices are being tested. Entropic repulsion between the polymer
      chains in a grafted brush of sufficient density causes the chains to extend in
      the direction perpendicular to the grafting surface in comparison to the position
      of unattached polymers. When nanoparticles having attractive interactions with
      the polymers are introduced into the solvent, these nanoparticles tend to
      infiltrate into the brush and reduce its extension. Under certain conditions, a
      sharp reduction in brush height extension can occur over a narrow range of
      nanoparticle concentrations in solution. We describe a way of controlling
      transport through polymer-functionalized nanochannels with nanoparticle
      additives, relying on the physics of nanoparticles and polymer brushes under
      confinement, and we suggest a blueprint for the creation of a tunable nanovalve.
      The nanovalve is modeled as a cylinder with a polymer brush grafted on its inside
      surface. Brush properties such as the chain length and the grafting density are
      chosen so that the brush chains extend into the center of the cylinder in the
      absence of nanoparticles, occluding the flux of analyte molecules through the
      pore. When nanoparticles that are attracted to the polymers are introduced into
      solution, they infiltrate into the brush and partially collapse it against the
      cylindrical grafting surface, opening space in the center of the cylinder through
      which analyte molecules can flow. The operation of such a nanovalve is analyzed
      via self-consistent field theory calculations in the strong-stretching
      approximation. Self-consistent field analysis is supported by Langevin dynamics
      simulations of the underlying coarse-grained model of the polymer-nanoparticle
      system. 

PMID- 26222481
TI  - Sources, topics and use of knowledge by coaches.
AB  - In recent years, the value of social learning approaches as part of the design
      and delivery of formalised coach development initiatives has gained credence in
      the literature. However, insight is currently lacking into the fundamental social
      dimensions that underpin coach learning. Accordingly, this study aimed to explore
      coaches' perceptions of their actual and preferred methods of acquiring new
      coaching knowledge, the types of knowledge they currently acquire and/or desire,
      and their application of new knowledge. Responses to an online survey, completed
      by practicing coaches (N = 320) in a range of sports and contexts, were analysed
      descriptively and inductively. Results revealed that coaches preferred, and
      mostly acquired, coaching knowledge from informal learning activities, especially
      when these permitted social interaction. Notably, however, formal coach education
      courses were also reported relatively frequently as a source of recent knowledge
      acquisition. Nevertheless, critical justification for and application of acquired
      knowledge was largely absent. Based on the findings, we suggest that, before
      social learning activities such as mentoring schemes and communities of practice
      are placed at the centre of formalised coach development provision, coach
      educators must put in place the support structures to better enable coaches to
      recognise and deal with the potentially mixed influences of the social milieu on
      coach learning, aiming to ensure that their informal development is sufficiently
      open-minded, reflective and critical. 

PMID- 26222482
TI  - Psychosocial Factors Associated With Withdrawal From the United Kingdom
      Collaborative Trial of Ovarian Cancer Screening After 1 Episode of Repeat
      Screening.
AB  - OBJECTIVE: The United Kingdom Collaborative Trial of Ovarian Cancer Screening
      (UKCTOCS) aims to establish the efficacy of 2 different ovarian cancer screening
      schedules. The psychosocial substudy examines the psychological factors
      associated with the screening program. METHODS: Women aged 50 to 75 years from 16
      UK gynecologic centers randomized to annual multimodal screening or ultrasound
      screening (US) groups were followed up for 7 years. Psychosocial data from women
      who withdrew from the study after a repeat screen were examined. RESULTS: Sixteen
      percent (3499/21,733) of women requiring a repeat screening test in addition to
      annual screen withdrew from the study: 12.9% (1560/12,073) from the multimodal
      group and 20.1% (1939/9660) from the US group. An estimated relative risk of
      withdrawal is 1.46 (95% confidence interval, 1.36-1.56; P <= 0.001) for the US
      arm. High anxiety trait and increased psychological morbidity significantly
      influenced withdrawal, even when age, screening center, and group were taken into
      account (P < 0.001). The risk of withdrawal decreased significantly the longer a
      woman stayed in UKCTOCS, irrespective of the number of screens and intensity in
      the preceding year. CONCLUSIONS: Withdrawal rate was greater in women undergoing
      US screening and in those who had repeats earlier in UKCTOCS. Having a high
      predisposition to anxiety, high current state anxiety, and above threshold
      general psychological morbidity all increased the withdrawal rate.

PMID- 26222483
TI  - SUMO-1 Promotes Ishikawa Cell Proliferation and Apoptosis in Endometrial Cancer
      by Increasing Sumoylation of Histone H4.
AB  - OBJECTIVES: To investigate the functional role of SUMO-1 on cell proliferation
      and apoptosis in endometrial cancer cells (Ishikawa line) and to explore the
      underlying regulatory mechanisms. METHODS: Different concentrations of estradiol
      (E2) and small interfering RNA (siRNA) targeting the SUMO-1 (siCo) were treated
      in Ishikawa cells, and then quantitative polymerase chain reaction was used to
      examine the expression of progesterone receptor (PR) expression in Ishikawa
      cells. Western blots were applied to validate histone H4 sumoylation. CCK8 assay
      and flow cytometry were performed to investigate cell proliferation and apoptosis
      in Ishikawa cells. RESULTS: Estradiol up-regulated the expression of PR messenger
      RNA, most obviously at 100 nM. SUMO-1 siRNA decreased the PR expression.
      Estradiol up-regulated H4 sumoylation and caused the increase of Ishikawa cell
      proliferation, whereas SUMO-1 siRNA down-regulated H4 sumoylation, inhibited the
      cell proliferation, and induced apoptosis. Furthermore, SUMO-1 siRNA-transfected
      cells were arrested in the S and G2/M phases and E2 increased the S and G2/M
      phases of Ishikawa cells. CONCLUSION: SUMO-1 regulates the Ishikawa cell
      proliferation and apoptosis by the sumoylation of histone H4.

PMID- 26222484
TI  - Long-Term Clinical Benefits of Neoadjuvant Chemotherapy in Women With Locally
      Advanced Cervical Cancer: Validity of Pathological Response as Surrogate Endpoint
      of Survival.
AB  - OBJECTIVE: Neoadjuvant chemotherapy (NACT) is a valid treatment option for women
      with locally advanced cervical cancer (LACC). This study aims to evaluate the
      impact of sociodemographic factors, clinical factors, and NACT regimens on
      survival endpoints. The role of pathological response to NACT as a surrogate
      endpoint of survival was also assessed. MATERIALS AND METHODS: Retrospective
      analysis of consecutive sample data from women with LACC (stages Ib2-IVa) who
      underwent NACT followed by radical surgery was performed. Response was classified
      as optimal response (including complete response and optimal partial response),
      suboptimal partial response, stable disease, and progressive disease. RESULTS:
      Four hundred forty-six women who had undergone surgery from 1992 to 2011 were
      analyzed. The overall optimal response was 35.4%. At a median follow-up of 12.7
      years, 165 women (37.0%) experienced recurrence or died. Increase in patient age
      at surgery, International Federation of Gynecology and Obstetrics stage III/IV
      versus stage Ib2, and lymph-node positivity versus negativity seemed to impact
      negatively on survival, whereas neoadjuvant platinum-Taxol-containing regimens
      (compared with platinum-based regimens) improved survival. Response to NACT could
      be considered a surrogate endpoint of survival. CONCLUSIONS: Age, International
      Federation of Gynecology and Obstetrics stage III/IV, lymph-node involvement, and
      type of NACT administered have a significant impact on survival. Response to NACT
      is a good surrogate endpoint of survival in patients with LACC.

PMID- 26222485
TI  - Role of Transdiaphragmatic Thoracic Exploration in Bulky Stage IIIC Ovarian
      Cancer Patients Who Underwent Diaphragmatic Surgery.
AB  - OBJECTIVES: This study was designed to validate the feasibility, effect on the
      new International Federation of Gynecology and Obstetrics (FIGO) staging, and
      surgical indications of transdiaphragmatic thoracic exploration (TDTE) without
      the use of thoracoscopy. METHODS: Patients with ovarian cancer who underwent TDTE
      after either diaphragm peritonectomy or full-thickness diaphragm resection
      between January 2009 and March 2014 were selected for our study. RESULTS: Twenty
      two patients with a median age of 53 years and a median level of CA125 at 1134
      U/mL before operation were included in our study. We found that 14/22 (63.6%)
      patients have pleural metastases and were diagnosed as FIGO stage IVB due to the
      TDTE process. Three patients had TDTE-related complications after surgery. We
      also found that 7 cases were performed with TDTE unintentionally, whereas
      intentional TDTE was performed in 15 patients including 5 cases with untapped
      pleural effusion, 4 with full-depth diaphragmatic invasion, 1 with positive
      pleural disease on computed tomography, and 5 with none of the reasons previously
      mentioned. CONCLUSIONS: Transdiaphragmatic thoracic exploration is a feasible
      procedure. The FIGO staging may be adjusted after TDTE. The surgical indications
      for TDTE should consider an untapped pleural effusion and full-depth
      diaphragmatic invasion.

PMID- 26222486
TI  - Multiple Cycles of Neoadjuvant Chemotherapy Associated With Poor Survival in
      Bulky Stage IIIC and IV Ovarian Cancer.
AB  - OBJECTIVE: The aim of this study was to determine the impact of neoadjuvant
      chemotherapy (NACT) on survival in patients with bulky stage IIIC and IV
      epithelial ovarian cancer. METHODS: Between January 2009 and December 2012, 408
      patients with ovarian cancer with extensive upper abdominal disease were
      reviewed. On the basis of the cycle number of NACT, patients were divided into 2
      groups, namely, primary debulking surgery (PDS) group, which included the
      patients who received no more than 1 cycle of NACT; and neoadjuvant chemotherapy
      followed by interval debulking surgery (NACT-IDS) group, which included the
      patients who received more than 1 cycle of NACT. All patients underwent
      cytoreductive surgery with the goal of optimal outcome (<=1 cm). Progression-free
      survival and overall survival were evaluated. RESULTS: There was no difference in
      surgical outcomes between PDS and NACT-IDS group, which was evaluated with either
      complete cytoreduction (41/376, 10.9% vs 6/32, 18.8%) or optimal cytoreduction
      (201/376, 53.5% vs 18/32, 56.2%). The median survival was 43.0 and 27.3 months in
      the PDS group and NACT-IDS group, with an estimated 5-year survival of 36% and
      31%, respectively (P = 0.032; hazard ratio, 0.59; 95% confidence interval, 0.36
      0.95). Complete cytoreduction, without bowel mesenteric carcinomatosis, and no
      more than 1 cycle of NACT were associated with lengthened survival by the
      multivariate analysis (P = 0.012, 0.025, and 0.036, respectively). CONCLUSIONS:
      Neoadjuvant chemotherapy was associated with poor survival of patients with bulky
      stage IIIC and IV ovarian cancer. A well-designed randomized trial with a better
      quality control of surgical procedures is needed to confirm the results.

PMID- 26222487
TI  - Vulvar Reconstruction Following Surgery for Vulvar Cancer Using a Stepladder V-Y
      Advancement Medial Thigh Flap.
AB  - OBJECTIVE: The aim of this study was to identify the risks and benefits of the
      stepladder V-Y advancement medial thigh flap for vulvovaginal reconstruction in
      comparison to direct skin closure. METHODS: Fifty-four patients with vulvar
      cancer treated in our hospital between 1992 and 2013 were enrolled in this study.
      The cohort group (group A) consisted of 25 patients who underwent surgery from
      August 2006 until April 2013. During this period, we changed our surgical
      paradigm to incorporate reconstructive plastic surgery immediately following
      surgery for vulvar cancer performed by gynecologic oncologists. The control group
      (group B) consisted of 29 patients treated between 1992 and August 2006. During
      this period, our surgical approach was limited to direct skin closure with no
      reconstructive plastic surgery. Perioperative findings and clinical outcomes were
      compared retrospectively. RESULTS: Patient characteristics and surgical
      procedures, other than the reconstructive surgery, were the same for the 2
      groups. The mean blood loss and operative times were similar, and there were no
      major complications in either group; however, the average length of hospital stay
      was significantly shorter in group A (P = 0.04). CONCLUSIONS: Stepladder V-Y
      advancement medial thigh flap lowers posttreatment morbidity and improves quality
      of life for patients with vulvar cancer. Rapid recovery from surgery is reflected
      in the short hospital stay, and it enables immediate induction of adjuvant
      therapy. It may possibly contribute to improved treatment outcome.

PMID- 26222488
TI  - The Effect of Cyclooxygenase-2 Expression in Uterine Carcinosarcoma on Survival:
      A Reassessment Based on Mature Data.
AB  - OBJECTIVE: To reassess the effect cyclooxygenase-2 (COX-2) expression in
      carcinosarcoma on survival based on mature 5-year survival data. METHOD: A
      comparison of 5-year survival of 27 patients with carcinosarcoma according to the
      presence of COX-2 immunohistochemical staining and staining score was performed.
      RESULTS: The 5-year survival of those with positive and negative COX-2 staining
      was statistically not different. However, there was a clear trend for more
      favorable 5-year survival in patients with a high staining score than in those
      with a low score, and the difference was of borderline significance (38.5% vs
      7.1%; P = 0.06). CONCLUSION: In view of the role of COX-2 in carcinogenesis, our
      finding that COX-2 expression may confer a better survival in patients with
      carcinosarcoma is intriguing. Larger studies are indicated to elucidate the
      effect of COX-2 expression on survival in patients with carcinosarcoma because
      this may have therapeutic implications.

PMID- 26222489
TI  - Research contributions on childhood obesity from a public-private partnership.
AB  - BACKGROUND: Childhood obesity remains a significant global problem with immediate
      and long-term individual health and societal consequences. Targets for change
      should include the most potent and predictive factors for obesity at all levels
      of the personal, social and physical environments. The Michael & Susan Dell
      Center for Healthy Living ('the Center') is a public-private partnership that was
      developed to address child health issues through research, service, and
      education. This overview paper introduces a special issue of seven articles on
      childhood obesity from the Center, and the implications of this research for
      obesity prevention. METHODS AND RESULTS: A review of the literature on public
      private partnerships was undertaken and key components of the partnership between
      the Michael & Susan Dell Foundation and the Center were compared for
      compatibility. The conceptual framework for Center research, based on social
      cognitive theory and the social-ecological model, is explained. An overview of
      papers in this special issue, relative to the conceptual framework, and the
      implications of this research for childhood obesity prevention, are provided.
      CONCLUSIONS: The public-private partnership that created the Michael & Susan Dell
      Center for Healthy Living has been instrumental in motivating the Center's
      academic faculty to focus their research on improvements in child, family and
      community health through etiologic, epidemiologic, methodologic and intervention
      research. This special issue extends this work and places particular emphasis on
      socioeconomic inequalities in addressing the obesity problem in the U.S. and
      worldwide.

PMID- 26222490
TI  - Experiences of facilitators or barriers in driving education from learner and
      novice drivers with ADHD or ASD and their driving instructors.
AB  - BACKGROUND: Little is known about whether individuals with autism spectrum
      disorder (ASD) or attention deficit hyperactive disorder (ADHD) experience any
      specific facilitators or barriers to driving education. OBJECTIVE: To explore the
      facilitators or barriers to driving education experienced by individuals with ASD
      or ADHD who obtained a learner's permit, from the perspective of the learner
      drivers and their driving instructors. METHODS: Data were collected from 33
      participants with ASD or ADHD, and nine of their driving instructors. RESULTS:
      Participants with ASD required twice as many driving lessons and more on-road
      tests than those with ADHD. Participants with ADHD repeated the written tests
      more than those with ASD. Driving license theory was more challenging for
      individuals with ADHD, whilst individuals with ASD found translating theory into
      practice and adjusting to "unfamiliar" driving situations to be the greatest
      challenges. CONCLUSION: Obtaining a driving license was associated with stressful
      training experience.

PMID- 26222491
TI  - Point mutation of cytochrome P450 2A6 (a polymorphic variant CYP2A6.25) confers
      new substrate specificity towards flavonoids.
AB  - CYP2A6 is a major hepatic member of the cytochrome P450 family in humans. Much
      variation in CYP2A6 levels and activity can be attributed to genetic
      polymorphisms of this gene. CYP2A6*25 comprises an amino acid substitution,
      F118L. To clarify the effect of the leucine substitution at position 118 in
      CYP2A6.25, this variant, wild type CYP2A6 and three additional variants
      consisting of artificial mutations at the substrate binding site (position 481)
      suggested by earlier reports using random mutagenesis studies [CYP2A6.1,
      CYP2A6.25, CYP2A6.1(F118A), CYP2A6.1(A481G) and CYP2A6.25(A481G)], were co
      expressed with NADPH-cytochrome P450 reductase in E. coli. The hydroxylase
      activity of these variants toward 7-ethoxycoumarin, coumarin, flavone, alpha
      naphthoflavone, flavanone and hydroxyflavanone were examined. All the mutants had
      lower activities for coumarin 7-hydroxylation than the wild type. All the mutants
      showed higher activities for flavone and alpha-naphthoflavone compared with
      CYP2A6.1. CYP2A6.1 had the highest flavanone 2'-hydroxylase activity, whereas
      CYP2A6.25 had the highest 6- and 4'-hydroxylase activities. CYP2A6.1(F118A),
      CYP2A6.1(A481G) and CYP2A6.25(A481G) had higher flavanone 3'-hydroxylase
      activities than CYP2A6.1 and CYP2A6.25. Furthermore, 4'-hydroxyflavanone was
      metabolized by CYP2A6.25. These results indicate that the CYP2A6.25 mutation
      confers new substrate specificity towards flavonoids.

PMID- 26222493
TI  - Maternal stress and plural breeding with communal care affect development of the
      endocrine stress response in a wild rodent.
AB  - Maternal stress can significantly affect offspring fitness. In laboratory
      rodents, chronically stressed mothers provide poor maternal care, resulting in
      pups with hyperactive stress responses. These hyperactive stress responses are
      characterized by high glucocorticoid levels in response to stressors plus poor
      negative feedback, which can ultimately lead to decreased fitness. In degus
      (Octodon degus) and other plural breeding rodents that exhibit communal care,
      however, maternal care from multiple females may buffer the negative impact on
      pups born to less parental mothers. We used wild, free-living degus to test this
      hypothesis. After parturition, we manipulated maternal stress by implanting
      cortisol pellets in 0%, 50-75%, or 100% of adult females within each social
      group. We then sampled pups for baseline and stress-induced cortisol, negative
      feedback efficacy, and adrenal sensitivity. From groups where all mothers were
      implanted with cortisol, pups had lower baseline cortisol levels and male pups
      additionally had weaker negative feedback compared to 0% or 50-75% implanted
      groups. Contrary to expectations, stress-induced cortisol did not differ between
      treatment groups. These data suggest that maternal stress impacts some aspects of
      the pup stress response, potentially through decreased maternal care, but that
      presence of unstressed mothers may mitigate some of these effects. Therefore, one
      benefit of plural breeding with communal care may be to buffer post-natal stress.

PMID- 26222492
TI  - "Slow" Voltage-Dependent Inactivation of CaV2.2 Calcium Channels Is Modulated by
      the PKC Activator Phorbol 12-Myristate 13-Acetate (PMA).
AB  - CaV2.2 (N-type) voltage-gated calcium channels (Ca2+ channels) play key roles in
      neurons and neuroendocrine cells including the control of cellular excitability,
      neurotransmitter / hormone secretion, and gene expression. Calcium entry is
      precisely controlled by channel gating properties including multiple forms of
      inactivation. "Fast" voltage-dependent inactivation is relatively well
      characterized and occurs over the tens-to- hundreds of milliseconds timeframe.
      Superimposed on this is the molecularly distinct, but poorly understood process
      of "slow" voltage-dependent inactivation, which develops / recovers over seconds
      to-minutes. Protein kinases can modulate "slow" inactivation of sodium channels,
      but little is known about if/how second messengers control "slow" inactivation of
      Ca2+ channels. We investigated this using recombinant CaV2.2 channels expressed
      in HEK293 cells and native CaV2 channels endogenously expressed in adrenal
      chromaffin cells. The PKC activator phorbol 12-myristate 13-acetate (PMA)
      dramatically prolonged recovery from "slow" inactivation, but an inactive control
      (4alpha-PMA) had no effect. This effect of PMA was prevented by calphostin C,
      which targets the C1-domain on PKC, but only partially reduced by inhibitors that
      target the catalytic domain of PKC. The subtype of the channel beta-subunit
      altered the kinetics of inactivation but not the magnitude of slowing produced by
      PMA. Intracellular GDP-beta-S reduced the effect of PMA suggesting a role for G
      proteins in modulating "slow" inactivation. We postulate that the kinetics of
      recovery from "slow" inactivation could provide a molecular memory of recent
      cellular activity and help control CaV2 channel availability, electrical
      excitability, and neurotransmission in the seconds-to-minutes timeframe. 

PMID- 26222494
TI  - Effects of postnatal estrogen manipulations on juvenile alloparental behavior.
AB  - Sex- and species-specific patterns of estrogen receptor (ER)-alpha expression are
      established early in development, which may contribute to sexual differentiation
      of behavior and determine male social organization. The current study
      investigated the effects of ERalpha and ERbeta activation during the second
      postnatal week on subsequent alloparental behavior and ERalpha expression in
      juvenile prairie voles. Male and female pups were treated daily with 17beta
      estradiol (E2, ERalpha/ERbeta agonist), PPT (selective ERalpha agonist), DPN
      (selective ERbeta agonist), or the oil vehicle on postnatal days (PD) 8-14.
      Alloparental behavior and ERalpha expression were examined at PD21. PPT treatment
      inhibited prosocial motivation in males and increased pup-directed aggression in
      both sexes. E2 and DPN had no apparent effect on behavior in either sex. PPT
      treated males had increased ERalpha expression in the medial preoptic area (MPN),
      medial amygdala (MEApd) and bed nucleus of the stria terminalis (BSTpr). DPN
      treatment also increased ERalpha expression in males, but only in the BSTpr.
      Female ERalpha expression was unaffected by treatment. These results support the
      hypothesis that ERalpha activation in early life is associated with less
      prosocial patterns of central ERalpha expression and alloparental behavior in
      males. The lack of an effect of E2 on behavior suggests that ERbeta may
      antagonize the effects of ERalpha on alloparental behavior. The results in DPN
      treated males suggest that ERalpha in the MEApd, and not the BSTpr, may be a
      primary determinant of alloparental behavior in males. 

PMID- 26222495
TI  - Mitogen-activated kinase pathway activation in epidermal lamellae in the acute
      stages of carbohydrate overload laminitis models and the effect of regional deep
      hypothermia on signalling pathways.
AB  - REASONS FOR PERFORMING STUDY: In sepsis models, mitogen-activated protein kinases
      (MAPKs) are reported to incite inflammatory injury to tissues and are purported
      to be a therapeutic target. OBJECTIVES: To assess MAPK signalling in lamellae in
      sepsis-related laminitis (SRL) at different time points after induction of
      laminitis via carbohydrate overload, and to determine the effect of regional deep
      hypothermia (RDH) on MAPK signalling. STUDY DESIGN: In vitro study using archived
      tissue samples. METHODS: Lamellar concentrations of MAPKs were assessed in
      archived lamellar samples from 2 studies: 1) the starch gruel model of SRL with 3
      groups (n = 6/group) of horses (control, onset of fever [DEV] Obel Grade 1
      lameness [OG1]); and 2) from limbs maintained at ambient (AMB) and hypothermic
      (ICE) temperatures (n = 6/group) in animals given a bolus of oligofructose.
      Immunoblotting and immunolocalisation were used to assess lamellar concentrations
      and cellular localisation of total and activated (phosphorylated) forms of p38
      MAPK, extracellular-regulated kinase (ERK) 1/2, and stress-activated protein
      kinase/c-jun N terminal kinase (SAPK/JNK) 1/2. RESULTS: Lamellar samples had
      statistically significant increased concentrations of activated ERK 1/2 at the
      onset of OG1 laminitis (vs. control) in the starch gruel model, but showed no
      significant change between ICE and AMB limbs in the RDH model. Phospho-SAPK/JNK
      1/2 exhibited a similar significant increase in the OG1 samples, but was also
      increased in ICE (vs. AMB) limbs. No statistically significant changes in
      lamellar p38 MAPK concentrations were noted. CONCLUSIONS: Increased
      concentrations of activated ERK 1/2 and SAPK/JNK in the acute stages of SRL
      indicate a possible role of these signalling proteins in lamellar injury.
      Signalling related to ERK 1/2 and SAPK/JNK 1/2 pathways should be further
      investigated to determine if these play a detrimental role in laminitis and may
      be therapeutic targets to be manipulated independently of RDH.

PMID- 26222496
TI  - Efficacy of topical cross-linked hyaluronic acid hydrogel in preventing post
      laminectomy/laminotomy fibrosis in a rat model.
AB  - Post-laminectomy/laminotomy epidural fibrosis (EF) has been implicated as an
      important cause of failed back syndrome (FBS). The various clinical approaches
      used to control EF yield mixed outcomes. Cross-linked hyaluronic acid hydrogel
      (cHA) was synthesized to increase mechanical stability and residence time. We
      evaluated the therapeutic attenuation of proliferative EF in
      laminectomy/laminotomy groups treated and not treated with cHA. A bilateral T11
      L1 total laminectomy or unilateral T12 laminotomy was done on four groups (n = 10
      each) of Sprague-Dawley rats and then histologically examined 2 months post
      surgery: (I) laminectomy group treated with and (II) not treated with cHA, (III)
      laminotomy group treated with and (IV) not treated with cHA. The grade of EF, the
      diameters within the spinal canal, dura mater thickness, and the area of the
      epidural space, subarachnoid space, and conus medullaris space were assessed. The
      cHA-treated subgroups (I, III) had a significantly lower grade of EF, thinner
      dura mater, and larger epidural and subarachnoid spaces than did the control
      subgroups (II, IV) (p < 0.05). The cHA formed a solid interpositional membrane
      barrier that prevented invasive fibrosis, and also helped reduce pathological
      changes to the adjacent structures. In conclusion, topically applied cHA is
      effective for reducing EF.

PMID- 26222497
TI  - Effect of Relative Decrease in Blood Hemoglobin Concentrations on Postoperative
      Morbidity in Patients Who Undergo Major Gastrointestinal Surgery.
AB  - IMPORTANCE: Delta hemoglobin (DeltaHb), defined as the difference between the
      preoperative hemoglobin (Hb) level and the nadir Hb level during a patient's
      hospitalization, may be associated with adverse outcomes even if the absolute
      level of Hb remains greater than the transfusion threshold of 7 g/dL. OBJECTIVE:
      To evaluate the association between DeltaHb and morbidity in patients who undergo
      major gastrointestinal surgery as an independent factor or combined with the
      nadir Hb concentration. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review
      of prospectively collected data on patients who underwent pancreatic, hepatic, or
      colorectal resection from January 1, 2010, through April 30, 2014, at Johns
      Hopkins Hospital were included in the study. Data regarding the DeltaHb
      concentration following surgery, nadir Hb level, and overall perioperative blood
      use were obtained and analyzed. Multivariable-adjusted logistic regression models
      were used to identify the preoperative factors associated with DeltaHb and the
      effect of DeltaHb on perioperative morbidity. The study and data analysis took
      place from January 22 through February 20, 2015. INTERVENTIONS: Major
      gastrointestinal surgery and packed red blood cell transfusion. MAIN OUTCOMES AND
      MEASURES: Overall morbidity and ischemic-specific complications. RESULTS: Of the
      4669 patients who underwent major gastrointestinal surgery, the median DeltaHb
      level after surgery was 40%. Patients with multiple comorbidities (American
      Society of Anesthesiologists Physical Status score of 3-4: odds ratio [OR], 1.96;
      95% CI, 1.30-2.97; P <.001; >=3 coexisting medical conditions: OR, 1.62; 95% CI,
      1.08-2.42; P = .001) and those who underwent pancreatic surgery (OR, 1.98; 95%
      CI, 1.18-3.33; P = .01) were at increased risk of having a DeltaHb of 50% or
      greater. Compared with patients who had a DeltaHb level of less than 50% and a
      nadir Hb level of 7 g/dL or greater, patients with a DeltaHb level of 50% or
      greater whose nadir Hb level was less than 7 g/dL were at a high risk of
      developing postoperative complications (OR, 6.60; 95% CI, 4.34-10.03; P < .001);
      in particular, a DeltaHb level of 50% or greater was strongly correlated with a
      risk of ischemic complications, even if the nadir Hb level was 7 g/dL or greater
      (OR, 5.68; 95% CI, 1.44-22.39; P = .01). CONCLUSIONS AND RELEVANCE: A DeltaHb
      level of 50% or greater following gastrointestinal surgery was associated with
      complications, especially ischemic adverse events, even if the nadir Hb level
      remained at 7 g/dL or greater.

PMID- 26222499
TI  - Virus-resistant pigs might help to stem next outbreak.
AB  - By genetically engineering pigs to degrade a crucial viral protein, livestock can
      be made less susceptible to foot and mouth disease virus. 

PMID- 26222498
TI  - Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets
      in Canine Endometrial Lesions.
AB  - Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine
      diseases in intact dogs, with pyometra being a life threatening disease. This
      study aimed to determine the gene expression profile of these lesions and
      potential biomarkers for closed-cervix pyometra, the most severe condition. Total
      RNA was extracted from 69 fresh endometrium samples collected from 21 healthy
      female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and
      nine closed-cervixes). Global gene expression was detected using the Affymetrix
      Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly
      composed of diestrus and CEH samples and the other by 12/15 mucometra and all
      pyometra samples. When comparing pyometra with other groups, 189 differentially
      expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8
      were among the top up-regulated genes detected in pyometra, further confirmed by
      external expression data. Notably, a particular molecular profile in pyometra
      from animals previously treated with exogenous progesterone compounds was
      observed in comparison with pyometra from untreated dogs as well as with other
      groups irrespective of exogenous hormone treatment status. In addition to S100A8
      and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6
      as well as LTF were detected in the pyometra from treated animals. Interestingly,
      closed pyometra was more frequently detected in treated dogs (64% versus 33%),
      with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This
      molecular signature associated with potential biomarkers and therapeutic targets,
      such as CXCL10 and COX2, should guide future clinical studies. Based on the gene
      expression profile we suggested that pyometra from progesterone treated dogs is a
      distinct molecular entity. 

PMID- 26222500
TI  - Regulation of the PI3K pathway through a p85alpha monomer-homodimer equilibrium.
AB  - The canonical action of the p85alpha regulatory subunit of phosphatidylinositol 3
      kinase (PI3K) is to associate with the p110alpha catalytic subunit to allow
      stimuli-dependent activation of the PI3K pathway. We elucidate a p110alpha
      independent role of homodimerized p85alpha in the positive regulation of PTEN
      stability and activity. p110alpha-free p85alpha homodimerizes via two
      intermolecular interactions (SH3:proline-rich region and BH:BH) to selectively
      bind unphosphorylated activated PTEN. As a consequence, homodimeric but not
      monomeric p85alpha suppresses the PI3K pathway by protecting PTEN from E3 ligase
      WWP2-mediated proteasomal degradation. Further, the p85alpha homodimer enhances
      the lipid phosphatase activity and membrane association of PTEN. Strikingly, we
      identified cancer patient-derived oncogenic p85alpha mutations that target the
      homodimerization or PTEN interaction surface. Collectively, our data suggest the
      equilibrium of p85alpha monomer-dimers regulates the PI3K pathway and disrupting
      this equilibrium could lead to disease development. 

PMID- 26222501
TI  - BRAF Fusion Analysis in Pilocytic Astrocytomas: KIAA1549-BRAF 15-9 Fusions Are
      More Frequent in the Midline Than Within the Cerebellum.
AB  - Pilocytic astrocytomas (PAs) are increasingly tested for KIAA1549-BRAF fusions.
      We used reverse transcription polymerase chain reaction for the 3 most common
      KIAA1549-BRAF fusions, together with BRAF V600E and histone H3.3 K27M analyses to
      identify relationships of these molecular characteristics with clinical features
      in a cohort of 32 PA patients. In this group, the overall BRAF fusion detection
      rate was 24 (75%). Ten (42%) of the 24 had the 16-9 fusion, 8 (33%) had only the
      15-9 fusion, and 1 (4%) of the patients had only the 16-11 fusion. In the PAs
      with only the 15-9 fusion, 1 PA was in the cerebellum and 7 were centered in the
      midline outside of the cerebellum, that is, in the hypothalamus (n = 4), optic
      pathways (n = 2), and brainstem (n = 1). Tumors within the cerebellum were
      negatively associated with fusion 15-9. Seven (22%) of the 32 patients had tumor
      related deaths and 25 of the patients (78%) were alive between 2 and 14 years
      after initial biopsy. Age, sex, tumor location, 16-9 fusion, and 15-9 fusion were
      not associated with overall survival. Thus, in this small cohort, 15-9 KIAA1549
      BRAF fusion was associated with midline PAs located outside of the cerebellum;
      these tumors, which are generally difficult to resect, are prone to recurrence. 

PMID- 26222503
TI  - The Effect of Multiprofessional Simulation-Based Obstetric Team Training on
      Patient-Reported Quality of Care: A Pilot Study.
AB  - INTRODUCTION: This study aimed to explore whether multiprofessional simulation
      based obstetric team training improves patient-reported quality of care during
      pregnancy and childbirth. METHODS: Multiprofessional teams from a large obstetric
      collaborative network in the Netherlands were trained in teamwork skills using
      the principles of crew resource management. Patient-reported quality of care was
      measured with the validated Pregnancy and Childbirth Questionnaire (PCQ) at 6
      weeks postpartum. Before the training, 76 postpartum women (sample I) completed
      the questionnaire 6 weeks postpartum. Three months after the training, another
      sample of 68 postpartum women (sample II) completed the questionnaire. RESULTS:
      In sample II (after the training), the mean (SD) score of 108.9 (10.9) on the PCQ
      questionnaire was significantly higher than the score of 103.5 (11.6) in sample I
      (before training) (t = 2.75, P = 0.007). The effect size of the increase in PCQ
      total score was 0.5. Moreover, the subscales "personal treatment during
      pregnancy" and "educational information" showed a significant increase after the
      team training (P < 0.001). Items with the largest increase in mean scores
      included communication between health care professionals, clear leadership,
      involvement in planning, and better provision of information. CONCLUSIONS:
      Despite the methodological restrictions of a pilot study, the preliminary results
      indicate that multiprofessional simulation-based obstetric team training seems to
      improve patient-reported quality of care. The possibility that this improvement
      relates to the training is supported by the fact that the items with the largest
      increase are about the principles of crew resource management, used in the
      training.

PMID- 26222504
TI  - Assessment of Community Pharmacists' Counseling Practices With Simulated Patients
      Who Have Minor Illness: A Pilot Study.
AB  - STATEMENT: A community pharmacist (CP) must provide counseling to consumers of
      nonprescription medicines and promote responsible self-medication. Previous
      studies indicate no available statistics on the proportion of pharmacies that
      provide cognitive services in Brazil. Furthermore, few studies have explored CPs'
      performance regarding patient-centred cognitive services in community pharmacies.
      Thus, quality improvement initiatives are needed for the responsible provision of
      self-medication to fully integrate Brazilian CPs into patient-centred cognitive
      services. Consequently, the present study's aim was to assess CPs' performance in
      the management of cases with minor symptoms using nonprescription medicines.

PMID- 26222502
TI  - Pharmacologic Wnt Inhibition Reduces Proliferation, Survival, and Clonogenicity
      of Glioblastoma Cells.
AB  - Wingless (Wnt) signaling is an important pathway in gliomagenesis and in the
      growth of stem-like glioma cells. Using immunohistochemistry to assess the
      translocation of beta-catenin protein, we identified intranuclear staining
      suggesting Wnt pathway activation in 8 of 43 surgical samples (19%) from adult
      patients with glioblastoma and in 9 of 30 surgical samples (30%) from pediatric
      patients with glioblastoma. Wnt activity, evidenced by nuclear beta-catenin in
      our cohort and high expression of its target AXIN2 (axis inhibitor protein 2) in
      published glioma datasets, was associated with shorter patient survival, although
      this was not statistically significant. We determined the effects of the
      porcupine inhibitor LGK974 on 3 glioblastoma cell lines with elevated AXIN2 and
      found that it reduced Wnt pathway activity by 50% or more, as assessed by T-cell
      factor luciferase reporters. Wnt inhibition led to suppression of growth,
      proliferation in cultures, and modest induction of cell death. LGK974 reduced
      NANOG messenger RNA levels and the fraction of cells expressing the stem cell
      marker CD133 in neurosphere cultures, induced glial differentiation, and
      suppressed clonogenicity. These data indicate that LGK974 is a promising new
      agent that can inhibit the canonical Wnt pathway in vitro, slow tumor growth, and
      deplete stem-like clonogenic cells, thereby providing further support for
      targeting Wnt in patients with glioblastoma. 

PMID- 26222506
TI  - Stream Physical Characteristics Impact Habitat Quality for Pacific Salmon in Two
      Temperate Coastal Watersheds.
AB  - Climate warming is likely to cause both indirect and direct impacts on the
      biophysical properties of stream ecosystems especially in regions that support
      societally important fish species such as Pacific salmon. We studied the seasonal
      variability and interaction between stream temperature and DO in a low-gradient,
      forested stream and a glacial-fed stream in coastal southeast Alaska to assess
      how these key physical parameters impact freshwater habitat quality for salmon.
      We also use multiple regression analysis to evaluate how discharge and air
      temperature influence the seasonal patterns in stream temperature and DO. Mean
      daily stream temperature ranged from 1.1 to 16.4 degrees C in non-glacial
      Peterson Creek but only 1.0 to 8.8 degrees C in glacial-fed Cowee Creek,
      reflecting the strong moderating influence glacier meltwater had on stream
      temperature. Peterson Creek had mean daily DO concentrations ranging from 3.8 to
      14.1 mg L(-1) suggesting future climate changes could result in an even greater
      depletion in DO. Mean daily stream temperature strongly controlled mean daily DO
      in both Peterson (R2=0.82, P<0.01) and Cowee Creek (R2=0.93, P<0.01). However, DO
      in Peterson Creek was mildly related to stream temperature (R2=0.15, P<0.01) and
      strongly influenced by discharge (R2=0.46, P<0.01) on days when stream
      temperature exceeded 10 degrees C. Moreover, Peterson Creek had DO values that
      were particularly low (<5.0 mg L(-1)) on days when discharge was low but also
      when spawning salmon were abundant. Our results demonstrate the complexity of
      stream temperature and DO regimes in coastal temperate watersheds and highlight
      the need for watershed managers to move towards multi-factor risk assessment of
      potential habitat quality for salmon rather than single factor assessments alone.

PMID- 26222505
TI  - Mathematical Modeling of Intravascular Blood Coagulation under Wall Shear Stress.
AB  - Increased shear stress such as observed at local stenosis may cause drastic
      changes in the permeability of the vessel wall to procoagulants and thus initiate
      intravascular blood coagulation. In this paper we suggest a mathematical model to
      investigate how shear stress-induced permeability influences the thrombogenic
      potential of atherosclerotic plaques. Numerical analysis of the model reveals the
      existence of two hydrodynamic thresholds for activation of blood coagulation in
      the system and unveils typical scenarios of thrombus formation. The dependence of
      blood coagulation development on the intensity of blood flow, as well as on
      geometrical parameters of atherosclerotic plaque is described. Relevant
      parametric diagrams are drawn. The results suggest a previously unrecognized role
      of relatively small plaques (resulting in less than 50% of the lumen area
      reduction) in atherothrombosis and have important implications for the existing
      stenting guidelines. 

PMID- 26222507
TI  - Is the first seizure epilepsy--and when?
AB  - OBJECTIVE: Epilepsy has recently been redefined to include a single unprovoked
      seizure if the probability of recurrence is >=60% over the following 10 years.
      This definition is based on the estimated risk of a third seizure after two
      unprovoked seizures, using the lower-limit 95% confidence interval (CI) at 4
      years, and does not account for the initially high recurrence rate after first
      ever seizure that rapidly falls with increasing duration of seizure freedom. We
      analyzed long-term outcomes after the first-ever seizure, and the influence of
      duration of seizure freedom on the likelihood of seizure recurrence, and their
      relevance to the new definition of epilepsy. METHODS: Prospective analysis of 798
      adults with a first-ever unprovoked seizure seen at a hospital-based first
      seizure clinic between 2000 and 2011. The likelihood of seizure recurrence was
      analyzed according to the duration of seizure freedom, etiology,
      electroencephalography (EEG), and neuroimaging findings. RESULTS: The likelihood
      of seizure recurrence at 10 years was >=60% in patients with epileptiform
      abnormalities on EEG or neuroimaging abnormalities, therefore, meeting the new
      definition of epilepsy. However, the risk of recurrence was highly time
      dependent; after a brief period (<=12 weeks) of seizure freedom, no patient group
      continued to fulfill the new definition of epilepsy. Of 407 patients who had a
      second seizure, the likelihood of a third seizure at 4 years was 68% (95% CI 63
      73%) and at 10 years was 85% (95% CI 79-91%). SIGNIFICANCE: The duration of
      seizure freedom following first-ever seizure substantially influences the risk of
      recurrence, with none of our patients fulfilling the new definition of epilepsy
      after a short period of seizure freedom. When a threshold was applied based on
      the 10-year risk of a third seizure from our data, no first-seizure patient group
      ever had epilepsy. These data may be utilized in a definition of epilepsy after a
      first-ever seizure.

PMID- 26222508
TI  - Heart failure as a general pandemic in Asia.
AB  - Heart failure (HF) is an epidemic in healthcare worldwide, including Asia. It
      appears that HF will become more serious in the near future, with the
      epidemiological transition and ageing of the population. However, in contrast to
      Western countries, information on HF epidemiology is still limited in Asia,
      particularly in South Asia. In this review, we will briefly summarize available
      information regarding the current and future burden of HF in Asia, which
      indicates the importance of both primary prevention of underlying diseases of HF
      and secondary prevention, including management of ischaemic HF, HF with preserved
      EF, and HF in the elderly. 

PMID- 26222509
TI  - Tunneling Plasmonics in Bilayer Graphene.
AB  - We report experimental signatures of plasmonic effects due to electron tunneling
      between adjacent graphene layers. At subnanometer separation, such layers can
      form either a strongly coupled bilayer graphene with a Bernal stacking or a
      weakly coupled double-layer graphene with a random stacking order. Effects due to
      interlayer tunneling dominate in the former case but are negligible in the
      latter. We found through infrared nanoimaging that bilayer graphene supports
      plasmons with a higher degree of confinement compared to single- and double-layer
      graphene, a direct consequence of interlayer tunneling. Moreover, we were able to
      shut off plasmons in bilayer graphene through gating within a wide voltage range.
      Theoretical modeling indicates that such a plasmon-off region is directly linked
      to a gapped insulating state of bilayer graphene, yet another implication of
      interlayer tunneling. Our work uncovers essential plasmonic properties in bilayer
      graphene and suggests a possibility to achieve novel plasmonic functionalities in
      graphene few-layers. 

PMID- 26222510
TI  - Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases.
AB  - Fibrosis is a consequence of chronic inflammation and the persistent accumulation
      of extracellular matrix, for which the cycle of tissue injury and repair becomes
      a predominant feature. Both the innate and adaptive immune systems play key roles
      in the progress of fibrosis. The recently identified subsets of innate lymphoid
      cells (ILCs), which are mainly localize to epithelial surfaces, have been
      characterized as regulators of chronic inflammation and tissue remodeling,
      representing a functional bridge between the innate and adaptive immunity.
      Moreover, recent research has implicated ILCs as potential contributing factors
      to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary
      fibrosis. Here, we will summarize and discuss the key roles of ILCs and their
      related factors in fibrotic diseases and their potential for translation to the
      clinic.

PMID- 26222512
TI  - An Investigation of the Effects of Different Pulse Patterns of Transcutaneous
      Electrical Nerve Stimulation (TENS) on Perceptual Embodiment of a Rubber Hand in
      Healthy Human Participants With Intact Limbs.
AB  - OBJECTIVE: The aim of this study was to investigate the strength of perceptual
      embodiment achieved during an adapted version of the rubber hand illusion (RHI)
      in response to a series of modified transcutaneous electrical nerve stimulation
      (TENS) pulse patterns with dynamic temporal and spatial characteristics which are
      more akin to the mechanical brush stroke in the original RHI. MATERIALS AND
      METHODS: A repeated-measures counterbalanced experimental study was conducted
      where each participant was exposed to four TENS interventions: continuous pattern
      TENS; burst pattern TENS (fixed frequency of 2 bursts per second of 100 pulses
      per second); amplitude-modulated pattern TENS (intensity increasing from zero to
      a preset level, then back to zero again in a cyclical fashion); and sham (no
      current) TENS. Participants rated the intensity of the RHI using a three-item
      numerical rating scale (each item was ranked from 0 to 10). Friedman's analysis
      of ranks (one-factor repeated measure) was used to test the differences in
      perceptual embodiment between TENS innervations; alpha was set at p <= 0.05.
      RESULTS: There were statistically significant differences in the intensity of
      misattribution and perceptual embodiment between sham and active TENS
      interventions, but no significant differences between the three active TENS
      conditions (amplitude-modulated TENS, burst TENS, and continuous TENS). Amplitude
      modulated and burst TENS produced significantly higher intensity scores for
      misattribution sensation and perceptual embodiment compared with sham (no
      current) TENS, whereas continuous TENS did not. CONCLUSION: The findings provide
      tentative, but not definitive, evidence that TENS parameters with dynamic spatial
      and temporal characteristics may produce more intense misattribution sensations
      and intense perceptual embodiment than parameters with static characteristics
      (e.g., continuous pulse patterns).

PMID- 26222511
TI  - Risk of Psychiatric Disorders following Irritable Bowel Syndrome: A Nationwide
      Population-Based Cohort Study.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is the most common functional
      gastrointestinal (GI) disorder observed in patients who visit general
      practitioners for GI-related complaints. A high prevalence of psychiatric
      comorbidities, particularly anxiety and depressive disorders, has been reported
      in patients with IBS. However, a clear temporal relationship between IBS and
      psychiatric disorders has not been well established. OBJECTIVE: We explored the
      relationship between IBS and the subsequent development of psychiatric disorders
      including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder,
      and sleep disorder. METHODS: We selected patients who were diagnosed with IBS
      caused by gastroenteritis, according to the data in the Taiwan National Health
      Insurance Research Database. A comparison cohort was formed of patients without
      IBS who were matched according to age and sex. The incidence rate and the hazard
      ratios (HRs) of subsequent new-onset psychiatric disorders were calculated for
      both cohorts, based on psychiatrist diagnoses. RESULTS: The IBS cohort consisted
      of 4689 patients, and the comparison cohort comprised 18756 matched control
      patients without IBS. The risks of depressive disorder (HR = 2.71, 95% confidence
      interval [CI] = 2.30-3.19), anxiety disorder (HR = 2.89, 95% CI = 2.42-3.46),
      sleep disorder (HR = 2.47, 95% CI = 2.02-3.02), and bipolar disorder (HR = 2.44,
      95% CI = 1.34-4.46) were higher in the IBS cohort than in the comparison cohort.
      In addition, the incidence of newly diagnosed depressive disorder, anxiety
      disorder, and sleep disorder remained significantly increased in all of the
      stratified follow-up durations (0-1, 1-5, >=5 y). CONCLUSIONS: IBS may increase
      the risk of subsequent depressive disorder, anxiety disorder, sleep disorder, and
      bipolar disorder. The risk ratios are highest for these disorders within 1 year
      of IBS diagnosis, but the risk remains statistically significant for more than 5
      years. Clinicians should pay particular attention to psychiatric comorbidities in
      IBS patients.

PMID- 26222526
TI  - Landscape Analysis of Adult Florida Panther Habitat.
AB  - Historically occurring throughout the southeastern United States, the Florida
      panther is now restricted to less than 5% of its historic range in one breeding
      population located in southern Florida. Using radio-telemetry data from 87 prime
      aged (>=3 years old) adult panthers (35 males and 52 females) during the period
      2004 through 2013 (28,720 radio-locations), we analyzed the characteristics of
      the occupied area and used those attributes in a random forest model to develop a
      predictive distribution map for resident breeding panthers in southern Florida.
      Using 10-fold cross validation, the model was 87.5 % accurate in predicting
      presence or absence of panthers in the 16,678 km2 study area. Analysis of
      variable importance indicated that the amount of forests and forest edge,
      hydrology, and human population density were the most important factors
      determining presence or absence of panthers. Sensitivity analysis showed that the
      presence of human populations, roads, and agriculture (other than pasture) had
      strong negative effects on the probability of panther presence. Forest cover and
      forest edge had strong positive effects. The median model-predicted probability
      of presence for panther home ranges was 0.81 (0.82 for females and 0.74 for
      males). The model identified 5579 km2 of suitable breeding habitat remaining in
      southern Florida; 1399 km2 (25%) of this habitat is in non-protected private
      ownership. Because there is less panther habitat remaining than previously
      thought, we recommend that all remaining breeding habitat in south Florida should
      be maintained, and the current panther range should be expanded into south
      central Florida. This model should be useful for evaluating the impacts of future
      development projects, in prioritizing areas for panther conservation, and in
      evaluating the potential impacts of sea-level rise and changes in hydrology. 

PMID- 26222530
TI  - Unilateral forearm muscle 18F-FDG uptake after using a smartphone.
AB  - F-FDG PET is a tool widely used in many indications, mainly for staging malignant
      neoplasm. A correct interpretation of images requires knowledge of physiological
      uptake. The most frequently encountered can be found in head and neck area
      (language, masticator muscles, and ocular muscles). Many of them can be limited
      through preventive care before the completion of the exam (e.g., no practicing
      physical activity, no chewing, no reading). Growth of telecommunication
      technology has spread the use of smartphones, leading to new uptake artifacts
      during the acquisition of PET images: a unilateral hyper metabolism of forearm
      muscles. 

PMID- 26222527
TI  - Cold Atmospheric Plasma Modified Electrospun Scaffolds with Embedded Microspheres
      for Improved Cartilage Regeneration.
AB  - Articular cartilage is prone to degeneration and possesses extremely poor self
      healing capacity due to inherent low cell density and the absence of a
      vasculature network. Tissue engineered cartilage scaffolds show promise for
      cartilage repair. However, there still remains a lack of ideal biomimetic tissue
      scaffolds which effectively stimulate cartilage regeneration with appropriate
      functional properties. Therefore, the objective of this study is to develop a
      novel biomimetic and bioactive electrospun cartilage substitute by integrating
      cold atmospheric plasma (CAP) treatment with sustained growth factor delivery
      microspheres. Specifically, CAP was applied to a poly(epsilon-caprolactone)
      electrospun scaffold with homogeneously distributed bioactive factors
      (transforming growth factor-beta1 and bovine serum albumin) loaded poly(lactic-co
      glycolic) acid microspheres. We have shown that CAP treatment renders electrospun
      scaffolds more hydrophilic thus facilitating vitronectin adsorption. More
      importantly, our results demonstrate, for the first time, CAP and microspheres
      can synergistically enhance stem cell growth as well as improve chondrogenic
      differentiation of human marrow-derived mesenchymal stem cells (such as increased
      glycosaminoglycan, type II collagen, and total collagen production). Furthermore,
      CAP can substantially enhance 3D cell infiltration (over two-fold increase in
      infiltration depth after 1 day of culture) in the scaffolds. By integrating CAP,
      sustained bioactive factor loaded microspheres, and electrospinning, we have
      fabricated a promising bioactive scaffold for cartilage regeneration. 

PMID- 26222531
TI  - Renal 123I-MIBG Scintigraphy Before and After Kidney Autotransplantation.
AB  - A 25-year-old man underwent an autotransplantation of his right kidney because of
      fibromuscular dysplasia-induced renal artery stenosis and subsequent
      hypertension. Since transplantation results in complete kidney denervation, it
      enabled assessment of renal sympathetic nerve activity changes using renal I-MIBG
      scintigraphy. Before and 2 weeks after transplantation I-MIBG, scintigraphy was
      performed. Uptake of I-MIBG in the left (control) kidney increased after
      transplantation with 4% at 15 minutes and 5% at 4 hours postinjection images,
      whereas I-MIBG uptake in the right transplanted kidney decreased with 21% at 15
      minutes and with 29% at 4 hours, demonstrating renal I-MIBG changes after
      denervation. 

PMID- 26222532
TI  - Can the Prognosis of Cardiac Resynchronization Therapy Be Predicted by Gated
      SPECT?
AB  - PURPOSE: The aim of this study was to evaluate the role of gated myocardial
      perfusion SPECT (GMPS) phase parameters (phase SD and histogram bandwidth) in
      predicting the short-term response to cardiac resynchronization therapy (CRT) as
      left ventricle (LV) remodeling and the long-term effect as all-cause mortality or
      cardiac transplantation and hospitalization for heart failure. PATIENTS AND
      METHODS: This prospective observational study included 63 consecutive patients
      undergoing CRT from May 2008 to April 2014. Before CRT, patients underwent
      evaluation of New York Heart Association functional class, standard 12-lead ECG,
      Tc-MIBI GMPS, and 2-dimensional echocardiography. The patients were grouped
      according to complete left bundle-branch block (CLBBB). Follow-up was done every
      6 months after pacemaker implantation. The short-term end point was reverse LV
      remodeling in 6 to 12 months follow-up, and the long-term primary end point was
      all-cause mortality or cardiac transplantation. The secondary end point was
      hospitalization for heart failure. RESULTS: Reverse LV remodeling showed in 60.9%
      (39/63) patients (74.5% CLBBB [35/47] vs 25.0% non-CLBBB [4/16], P < 0.001).
      Phase SD less than 55 degrees, CLBBB, and left atrium diameter were independent
      predictive factors for reverse LV remodeling. At a median follow-up of 39.76
      months, there were 17 deaths and 2 transplantations (17.0% CLBBB vs 68.8% non
      CLBBB, P < 0.001). Seventeen patients required hospitalization more than once for
      heart failure, and 2 underwent heart transplantation (14.9% CLBBB vs 62.5% non
      CLBBB, P < 0.001). Multivariate logistic regression showed that only CLBBB was an
      independent predictive factor for both end points. CONCLUSIONS: The GMPS
      parameters were not independent predictive factors for all-cause mortality or
      cardiac transplantation and hospitalization for heart failure.

PMID- 26222533
TI  - Reducing perceived pain levels during nonbreast lymphoscintigraphy.
AB  - PURPOSE: The aim of this study was to quantify the reduction of perceived pain
      levels during lymphoscintigraphy for melanoma by altering the pH of the Tc-sulfur
      colloid to near the physiologic value of 7.40. PATIENTS AND METHODS: This is an
      institutional review board- and Food and Drug Administration-approved randomized,
      double-blinded, prospective crossover trial, registered with clinicaltrials.org.
      Before beginning the procedure and after signing informed consent, 60 serial
      enrollees presenting for sentinel lymph node imaging of melanoma of the thorax
      and appendicular structures completed a questionnaire addressing background
      information, administered by a research support nurse.An investigator (N.H.)
      prepared the injections to be used and labeled them such that no one else could
      discover which injections contained standard-of-care solution and which contained
      the pH-altered solution (buffered to near pH 7.40 using sodium bicarbonate).After
      each injection, the enrollee was asked by a research support nurse to quantify
      the pain of each injection using a scale of 0 to 10. The injection site location
      (head, thorax, appendicular structures, and other) was also recorded. RESULTS:
      Sixty subjects were enrolled in the study, of which 57 had complete data. On
      average, there was a significant mean (SD) decrease of 1.42 (2.17) points (95%
      confidence interval, 0.85-2.00) on a pain scale of 0 to 10 when the buffered
      injections were used as compared with the standard-of-care injections (P <
      0.0001). Ordering of injections did not significantly affect perceived pain
      scores. CONCLUSIONS: The use of sodium bicarbonate to buffer the pH of Tc-sulfur
      colloid to near the physiologic value of 7.40 significantly reduced perceived
      pain levels during nonbreast lymphoscintigraphy.

PMID- 26222534
TI  - 90Y Radioembolization Lung Shunt Fraction in Primary and Metastatic Liver Cancer
      as a Biomarker for Survival.
AB  - OBJECTIVE: The aim of this study was to investigate pre-90Y lung shunt fraction
      (LSF) as a prognostic factor for overall survival (OS) in 90Y (resin/glass)
      planning 99mTc-MAA hepatopulmonary shunt studies for primary (hepatocellular
      carcinoma [HCC], intrahepatic cholangiocarcinoma) and metastatic liver tumors.
      METHODS: A total of 366 consecutive patients with primary and metastatic liver
      tumors underwent pre-90Y shunt study and 90Y radioembolization (mean age, 59.2
      years; 55% were male). MAA (mean activity, 3.65 mCi) was administered via the
      proper hepatic artery. Shunted lung activity was obtained by planar scintigraphy.
      Median LSF values for primary tumors and metastases were compared with OS from
      first 90Y therapy via Kaplan-Meier estimation and log-rank test. Correlations
      between LSF and tumor involvement on baseline cross-sectional imaging were
      analyzed using Pearson coefficient (r). Patients with LSF of greater than 20%
      were deemed unsuitable for 90Y. RESULTS: The study included 79 (21.5%)
      colorectal, 73 (20%) neuroendocrine, 70 (19.1%) HCC, 40 (10.9%) intrahepatic
      cholangiocarcinoma, 40 (10.9%) melanoma, 20 (5.5%) breast, and 44 (12%) other
      tumors including lung and pancreatic cancers. Lung shunt fractions of less than
      10% and 10% to 20% were observed in 235 patients (64.2%) and 131 patients
      (35.8%), respectively. Median LSFs were as follows: colorectal cancer (7.60%),
      neuroendocrine tumor (7.01%), HCC (11.47%), cholangiocarcinoma (7.00%), melanoma
      (6.00%), breast cancer (7.00%), and others, including lung and pancreatic
      metastases to the liver (8.36%). The HCC median LSF was significantly higher than
      that in non-HCC tumors, 11.47% versus 7.10% (P < 0.001). High LSF (>= 10%) in HCC
      correlated with poorer survival from first 90Y compared with low LSF (<10%; 4.5
      vs 16.4 months, P = 0.003). Similarly, for metastatic disease, high LSF
      demonstrated significantly poorer survival compared with low LSF in colorectal
      liver metastases (13.5 vs 7.0 months, P = 0.013), neuroendocrine liver metastases
      (33.0 vs 9.1 months, P < 0.001), and melanoma liver metastases (12.0 vs 5.0
      months, P = 0.03). No correlation between tumor burden on cross-sectional imaging
      and LSF was observed (r = 0.35). CONCLUSIONS: In patients who are candidates for
      90Y therapy, higher LSF is a poor prognostic factor for OS in HCC and metastatic
      liver tumors.

PMID- 26222535
TI  - Oral Cholecystagogue Cholescintigraphy: A Systematic Review of Fatty Meal
      Options.
AB  - OBJECTIVES: Intermittent unavailability of sincalide for determination of
      gallbladder ejection fraction (GBEF) prompted increased usage of fatty meal
      cholecystagogues (FMCs). The aim of this systematic review was to identify the
      state of current FMC options in cholescintigraphy, focusing on the quality of
      corresponding normal GBEF values. METHODS: We performed an extensive literature
      search of the MEDLINE, Cochrane, and CINAHL databases without date or language
      restrictions with a broad spectrum of search terms. Selection criteria required
      both that the study use a FMC as part of a stimulated GBEF examination to gather
      data on normal volunteers or patients without evidence of gastrointestinal
      disease and that the meal used be described sufficiently for emulation. A
      cumulative point system was used to grade the quality of normal GBEF values: 1
      point for screening ultrasound, 1 point for detailed screening questionnaire, 1
      point for 20 or greater number of participants in a study, 1 additional point for
      60 or greater number of participants in a study, 0.5 points for cursory screening
      questions, and 0 points when no screening process was mentioned. The meal was
      expressed in grams of fat per volume, when available. RESULTS: Twelve studies met
      inclusion criteria out of 15 studies claiming to report normal values. Two
      studies (17%) achieved a score of 3, 5 studies (42%) at 2 to 2.5, 3 studies (25%)
      at 1 to 1.5, and the remaining 2 studies (17%) at 0 to 0.5. Total number of
      participants examined ranged from 6 to 100. Meal composition varied widely. In 1
      study, sham feeding was used. Most meals had components that could present
      problems to patients with relatively common dietary restrictions (ie, lactose
      intolerance, egg protein allergy, etc). Results for proposed normal values varied
      widely (from 16.3% to 85.6%). The commercial fatty meal products of Humana Infant
      Formula 1 and Ensure Plus offered the highest-quality normal values. CONCLUSIONS:
      There is a need to establish high-quality normal GBEF range for a ubiquitous
      fatty meal (ie, a meal that would be widely available, easy to prepare,
      inexpensive, and free of sensitivity-provoking ingredients). A corn oil emulsion,
      has immense potential as an ideal FMC, limited currently only by its lack of
      established normal values. Currently, the highest-quality normal GBEF values
      available for FMC exist for 2 commercial products, Humana Infant Formula 1 and
      Ensure Plus. However, these products may not be readily available at some
      institutions, and neither one is free from dietary restrictions.

PMID- 26222536
TI  - Factors that affect PERCIST-defined test-retest comparability: an exploration of
      feasibility in routine clinical practice.
AB  - PURPOSE: The aim of this study was to evaluate the factors affecting the
      comparability of F-FDG PET/CT scans using the PERSIST criteria for treatment
      response evaluation in a clinical PET/CT unit. PATIENTS AND METHODS: Patients
      diagnosed with esophageal cancer were assessed for treatment response by
      comparing 2 F-FDG PET/CT scans, at baseline (PET 1) and 1 month after the end of
      induction chemoradiation (PET 2). According to the PERCIST recommendations,
      patients with mean SUV normalized by the lean body mass within reference volume
      of interest that changed less than 0.3 unit and less than 20% were deemed as
      comparable. Absolute differences of body weight, blood glucose level, activity of
      F-FDG, and uptake time between the 2 scans were computed. Binary logistic
      regression was used to identify the predictive factors, and receiver operating
      characteristic curves were used for thresholds. P < 0.05 was considered
      statistically significant. RESULTS: Sixty-nine subjects were identified. The mean
      (SD) values at PET 0 and PET 2 were 5.9 (1.04) mmol/L and 6.2 (1.06) mmol/L (P =
      0.013), 54.6 (10.0 kg) and 53.3 (10.3 kg) (P = 0.013), 7.7 (1.3 mCi) and 7.6 (1.5
      mCi) (P = 0.349), as well as 74.2 (12.4) minutes and 73.0 (12.3) minutes (P =
      0.539), for blood glucose level, body weight, injected activity, and uptake time,
      respectively. Seventeen (24.6%) failed to match the PERCIST-defined comparability
      criteria. Case-based discrepancies (mean [SD]) were 0.76 (0.62) mmol/L, 3.4 (2.9)
      kg, 0.8 (0.7) mCi, and 11.7 (9.8) minutes for blood glucose, body weight,
      injected activity, and uptake time, respectively, of which only uptake time
      significantly affected comparability (P = 0.046; odds ratio, 1.06; 95% confidence
      interval, 1.00-1.12), with a limit of 2.2-minute discrepancy identified as the
      requirement for 100% comparability. CONCLUSIONS: Uptake time had the strongest
      effect on PERCIST-defined comparability. Therefore, for response assessment
      scans, reference to initial scans for determination of optimal uptake time is
      recommended.

PMID- 26222537
TI  - Multiple Myeloma and Abdominal Aortic Aneurysm on Myocardial Perfusion Raw
      Images.
AB  - Reviewing cine display of planar projections just after data acquisition of
      myocardial perfusion imaging is helpful not only for checking quality of the
      study but also for better interpretation of incidental findings by acquiring more
      helpful images. We present a patient with significant skeletal Tc-MIBI uptake
      accompanied by a large photopenic area in abdominal cavity in myocardial
      perfusion imaging raw images that were further confirmed as multiple myeloma and
      thrombotic abdominal aortic aneurysm, respectively. 

PMID- 26222538
TI  - An Assessment of the Expected Cost-Effectiveness of Quadrivalent Influenza
      Vaccines in Ontario, Canada Using a Static Model.
AB  - Ontario, Canada, immunizes against influenza using a trivalent inactivated
      influenza vaccine (IIV3) under a Universal Influenza Immunization Program (UIIP).
      The UIIP offers IIV3 free-of-charge to all Ontarians over 6 months of age. A
      newly approved quadrivalent inactivated influenza vaccine (IIV4) offers wider
      protection against influenza B disease. We explored the expected cost-utility and
      budget impact of replacing IIV3 with IIV4, within the context of Ontario's UIIP,
      using a probabilistic and static cost-utility model. Wherever possible,
      epidemiological and cost data were obtained from Ontario sources. Canadian or
      U.S. sources were used when Ontario data were not available. Vaccine efficacy for
      IIV3 was obtained from the literature. IIV4 efficacy was derived from meta
      analysis of strain-specific vaccine efficacy. Conservatively, herd protection was
      not considered. In the base case, we used IIV3 and IIV4 prices of $5.5/dose and
      $7/dose, respectively. We conducted a sensitivity analysis on the price of IIV4,
      as well as standard univariate and multivariate statistical uncertainty analyses.
      Over a typical influenza season, relative to IIV3, IIV4 is expected to avert an
      additional 2,516 influenza cases, 1,683 influenza-associated medical visits, 27
      influenza-associated hospitalizations, and 5 influenza-associated deaths. From a
      societal perspective, IIV4 would generate 76 more Quality Adjusted Life Years
      (QALYs) and a net societal budget impact of $4,784,112. The incremental cost
      effectiveness ratio for this comparison was $63,773/QALY. IIV4 remains cost
      effective up to a 53% price premium over IIV3. A probabilistic sensitivity
      analysis showed that IIV4 was cost-effective with a probability of 65% for a
      threshold of $100,000/QALY gained. IIV4 is expected to achieve reductions in
      influenza-related morbidity and mortality compared to IIV3. Despite not
      accounting for herd protection, IIV4 is still expected to be a cost-effective
      alternative to IIV3 up to a price premium of 53%. Our conclusions were robust in
      the face of sensitivity analyses. 

PMID- 26222539
TI  - The Impact of the Network Topology on the Viral Prevalence: A Node-Based
      Approach.
AB  - This paper addresses the impact of the structure of the viral propagation network
      on the viral prevalence. For that purpose, a new epidemic model of computer
      virus, known as the node-based SLBS model, is proposed. Our analysis shows that
      the maximum eigenvalue of the underlying network is a key factor determining the
      viral prevalence. Specifically, the value range of the maximum eigenvalue is
      partitioned into three subintervals: viruses tend to extinction very quickly or
      approach extinction or persist depending on into which subinterval the maximum
      eigenvalue of the propagation network falls. Consequently, computer virus can be
      contained by adjusting the propagation network so that its maximum eigenvalue
      falls into the desired subinterval. 

PMID- 26222541
TI  - Conductive-AFM Patterning of Organic Semiconductors.
AB  - Using a conductive atomic force microscope (c-AFM) redox-writing technique, it is
      shown that it is possible to locally, and reversibly, pattern conducting, and
      nonconducting features on the surface of a low molecular weight aniline-based
      organic (semi)-conductor thin film using a commercial c-AFM. It is shown that
      application of a voltage between the tip and sample causes localized redox
      reactions at the surface without damage. 

PMID- 26222540
TI  - Inbreeding Ratio and Genetic Relationships among Strains of the Western Clawed
      Frog, Xenopus tropicalis.
AB  - The Western clawed frog, Xenopus tropicalis, is a highly promising model
      amphibian, especially in developmental and physiological research, and as a tool
      for understanding disease. It was originally found in the West African rainforest
      belt, and was introduced to the research community in the 1990s. The major
      strains thus far known include the Nigerian and Ivory Coast strains. However, due
      to its short history as an experimental animal, the genetic relationship among
      the various strains has not yet been clarified, and establishment of inbred
      strains has not yet been achieved. Since 2003 the Institute for Amphibian Biology
      (IAB), Hiroshima University has maintained stocks of multiple X. tropicalis
      strains and conducted consecutive breeding as part of the National BioResource
      Project. In the present study we investigated the inbreeding ratio and genetic
      relationship of four inbred strains at IAB, as well as stocks from other
      institutions, using highly polymorphic microsatellite markers and mitochondrial
      haplotypes. Our results show successive reduction of heterozygosity in the genome
      of the IAB inbred strains. The Ivory Coast strains clearly differed from the
      Nigerian strains genetically, and three subgroups were identified within both the
      Nigerian and Ivory Coast strains. It is noteworthy that the Ivory Coast strains
      have an evolutionary divergent genetic background. Our results serve as a guide
      for the most effective use of X. tropicalis strains, and the long-term
      maintenance of multiple strains will contribute to further research efforts.

PMID- 26222543
TI  - Design and Synthesis of Nonequilibrium Systems.
AB  - The active transport of ions and molecules across cell membranes is essential to
      creating the concentration gradients that sustain life in all living organisms,
      be they bacteria, fungi, plants, animals or Homo sapiens. Nature uses active
      transport everywhere for everything. Molecular biologists have long been
      attracted to the study of active transport and continue to this day to
      investigate and elucidate the tertiary structures of the complex motor proteins
      that sustain it, while physicists, interested in nonequilibrium statistical
      mechanics, have developed theoretical models to describe the driven ratcheting
      motions that are crucial to its function. The increasingly detailed understanding
      that contemporary science has acquired relating to active transport, however, has
      yet to lead to the design and construction of artificial molecular motors capable
      of employing ratchet-driven motions that can also perform work against
      concentration gradients. Mechanically interlocked molecules (MIMs) in the form of
      pseudo- and semirotaxanes are showing some encouraging signs in meeting these
      goals. This review summarizes recent progress in making artificial molecular
      motors that can perform work by "pumping" tetracationic rings into high-energy
      states. The launching pad is a bistable [2]rotaxane whose dumbbell component
      contains two electron-donating recognition sites, one, a tetrathiafulvalene (TTF)
      unit, which interacts more strongly with the ring component, cyclobis(paraquat-p
      phenylene) (CBPQT(4+)), containing two electron-accepting bipyridinium units,
      than does the other 1,5-dioxynaphthalene (DNP) unit. Switching can be induced
      electrochemically by oxidizing the TTF unit to a TTF(*+) radical cation,
      whereupon Coulombic repulsion takes care of moving the ring to the DNP unit.
      Reduction of the radical cation resets the switch. Molecular switches operate at,
      or close to, equilibrium. Any work done during one switching event is undone
      during the reset. Molecular motors, on the other hand, rely on a flux of energy,
      and a ratchet mechanism to make periodic changes to the potential energy surface
      of a system in order to move molecules uphill to higher energy states. Forging a
      path from molecular switches to motors involved designing a molecular pump
      prototype. An asymmetric dumbbell with a 2-isopropylphenyl (neutral) end and a
      3,5-dimethylpyridinium (charged) end with a DNP recognition site to entice
      CBPQT(4+) rings out of solution exhibits relative unidirectional movement of the
      rings with respect to the dumbbell. Redox chemistry does the trick. During the
      oxidative cycle, the rings enter the dumbbell by passing over the neutral end
      onto the recognition site; in the reduction cycle, much of the recognition is
      lost and the rings find their way back into solution by leaving the dumbbell from
      the charged end. This on-one-end, off-the-other process can be repeated over and
      over again using light as the energy source in the presence of a photosensitizer
      and a compound that shuttles electrons back and forth. Although this prototype
      demonstrates ratchet-driven translational motion, no work is done. A ring enters
      the dumbbell from one end and leaves from the other end. Another deficiency of
      the prototype is the fact that, although the recognition site is muted on
      reduction, it retains some attraction for the ring. What if the recognition site
      was attractive initially and then became repulsive? This question was answered by
      turning to radical chemistry and employing the known stabilization behavior of a
      bipyridinium radical cation and the bisradical dication, generated on reduction
      of the CBPQT(4+) ring, to pluck rings out of solution and thread them over the
      charged end of the pump portion of a semidumbbell. On subsequent oxidation, the
      pump is primed and the rings pass through a one-way door, given a little thermal
      energy, onto a collecting-chain where they find themselves accumulating where
      they would rather not be present. In this manner, an artificial molecular pump
      mimics the pumping machinery commonplace in biological systems. Looking beyond
      this state-of-the-art artificial molecular pump, we discuss, from a theoretical
      standpoint, the measures that would need to be taken in order to render its
      operation autonomous. 

PMID- 26222542
TI  - Pharmacological Suppression of CNS Scarring by Deferoxamine Reduces Lesion Volume
      and Increases Regeneration in an In Vitro Model for Astroglial-Fibrotic Scarring
      and in Rat Spinal Cord Injury In Vivo.
AB  - Lesion-induced scarring is a major impediment for regeneration of injured axons
      in the central nervous system (CNS). The collagen-rich glial-fibrous scar
      contains numerous axon growth inhibitory factors forming a regeneration-barrier
      for axons. We demonstrated previously that the combination of the iron chelator
      2,2'-bipyridine-5,5'-decarboxylic acid (BPY-DCA) and 8-Br-cyclic AMP (cAMP)
      inhibits scar formation and collagen deposition, leading to enhanced axon
      regeneration and partial functional recovery after spinal cord injury. While BPY
      DCA is not a clinical drug, the clinically approved iron chelator deferoxamine
      mesylate (DFO) may be a suitable alternative for anti-scarring treatment (AST).
      In order to prove the scar-suppressing efficacy of DFO we modified a recently
      published in vitro model for CNS scarring. The model comprises a co-culture
      system of cerebral astrocytes and meningeal fibroblasts, which form scar-like
      clusters when stimulated with transforming growth factor-beta (TGF-beta). We
      studied the mechanisms of TGF-beta-induced CNS scarring and compared the
      efficiency of different putative pharmacological scar-reducing treatments,
      including BPY-DCA, DFO and cAMP as well as combinations thereof. We observed
      modulation of TGF-beta-induced scarring at the level of fibroblast proliferation
      and contraction as well as specific changes in the expression of extracellular
      matrix molecules and axon growth inhibitory proteins. The individual and
      combinatorial pharmacological treatments had distinct effects on the cellular and
      molecular aspects of in vitro scarring. DFO could be identified as a putative
      anti-scarring treatment for CNS trauma. We subsequently validated this by local
      application of DFO to a dorsal hemisection in the rat thoracic spinal cord. DFO
      treatment led to significant reduction of scarring, slightly increased
      regeneration of corticospinal tract as well as ascending CGRP-positive axons and
      moderately improved locomotion. We conclude that the in vitro model for CNS
      scarring is suitable for efficient pre-screening and identification of putative
      scar-suppressing agents prior to in vivo application and validation, thus saving
      costs, time and laboratory animals. 

PMID- 26222544
TI  - Windows of opportunity for physical activity in the prevention of obesity.
AB  - Tackling increasing rates of obesity is likely to be a defining feature of health
      care over the next several decades. Adult obesity is a persistent and treatment
      resistant problem. Consequently, an emerging theme in the literature is to
      commence prevention efforts earlier in the developmental time course. This view
      is based primarily on epidemiological data demonstrating a link between traits
      manifesting early during development and increased obesity risk in adulthood.
      Physical activity is a perennial factor in discussions of obesity prevention.
      However, the optimal timing and type of physical activity interventions to
      commence remains unclear. Critical developmental windows of plasticity may afford
      time-limited opportunities to shape body composition across the life course;
      however, physical activity has not been explicitly considered in these
      discussions. Although animal models suggest that physical activity commenced
      earlier in development has differential effects on obesity onset compared to
      physical activity commenced in adulthood, human research is lacking. In this
      conceptual review, we consider physical activity during critical developmental
      periods as a way to mitigate obesity risk later in life. 

PMID- 26222545
TI  - Challenges from Tuberculosis Diagnosis to Care in Community-Based Active Case
      Finding among the Urban Poor in Cambodia: A Mixed-Methods Study.
AB  - BACKGROUND: While community-based active case finding (ACF) for tuberculosis (TB)
      holds promise for increasing early case detection among hard-to-reach
      populations, limited data exist on the acceptability of active screening. We
      aimed to identify barriers and explore facilitators on the pathway from diagnosis
      to care among TB patients and health providers. METHODS: Mixed-methods study. We
      administered a survey questionnaire to, and performed in-depth interviews with,
      TB patients identified through ACF from poor urban settlements in Phnom Penh,
      Cambodia. Additionally, we conducted focus group discussions and in-depth
      interviews with community and public health providers involved in ACF,
      respectively. RESULTS: Acceptance of home TB screening was strong among key
      stakeholders due to perceived reductions in access barriers and in direct and
      indirect patient costs. Privacy and stigma were not an issue. To build trust and
      facilitate communication, the participation of community representatives
      alongside health workers was preferred. Most health providers saw ACF as
      complementary to existing TB services; however, additional workload as a result
      of ACF was perceived as straining operating capacity at public sector sites.
      Proximity to a health facility and disease severity were the strongest
      determinants of prompt care-seeking. The main reasons reported for delays in
      treatment-seeking were non-acceptance of diagnosis, high indirect costs related
      to lost income/productivity and transportation expenses, and anticipated side
      effects from TB drugs. CONCLUSIONS: TB patients and health providers considered
      home-based ACF complementary to facility-based TB screening. Strong engagement
      with community representatives was believed critical in gaining access to high
      risk communities. The main barriers to prompt treatment uptake in ACF were
      refusal of diagnosis, high indirect costs, and anticipated treatment side
      effects. A patient-centred approach and community involvement were essential in
      mitigating barriers to care in marginalised communities.

PMID- 26222546
TI  - Multidimensional Prognostic Index in Association with Future Mortality and Number
      of Hospital Days in a Population-Based Sample of Older Adults: Results of the EU
      Funded MPI_AGE Project.
AB  - BACKGROUND: The Multidimensional Prognostic Index (MPI) has been found to predict
      mortality in patients with a variety of clinical conditions. We aimed to assess
      the association of the MPI with future mortality and number of in-hospital days
      for the first time in a population-based cohort. METHODS: The study population
      consisted of 2472 persons, aged 66-99 years, from the Swedish National Study on
      Aging and Care in Kungsholmen, Sweden, who underwent the baseline visit 2001-4,
      and were followed up >10 years for in-hospital days and >12 years for mortality.
      The MPI was a modified version of the original and aggregated seven domains
      (personal and instrumental activities of daily living, cognitive function,
      illness severity and comorbidity, number of medications, co-habitation status,
      and nutritional status). The MPI score was divided into risk groups: low, medium
      and high. Number of in-hospital days (within 1, 3 and 10 years) and mortality
      data were derived from official registries. All analyses were age-stratified
      (sexagenarians, septuagenarians, octogenarians, nonagenarians). RESULTS: During
      the follow-up 1331 persons (53.8%) died. Laplace regression models, suggested
      that median survival in medium risk groups varied by age from 2.2-3.6 years
      earlier than for those in the corresponding low risk groups (p = 0.002-p<0.001),
      and median survival in high risk groups varied by age from 3.8-9.0 years earlier
      than for corresponding low risk groups (p<0.001). For nonagenarians, the median
      age at death was 3.8 years earlier in the high risk group than for the low risk
      group (p<0.001). The mean number of in-hospital days increased significantly with
      higher MPI risk score within 1 and 3 years for people of each age group.
      CONCLUSION: For the first time, the effectiveness of MPI has been verified in a
      population-based cohort. Higher MPI risk scores associated with more days in
      hospital and with fewer years of survival, across a broad and stratified age
      range.

PMID- 26222547
TI  - Clonal Occurrence of Salmonella Weltevreden in Cultured Shrimp in the Mekong
      Delta, Vietnam.
AB  - This study investigated the occurrence, serovar and antimicrobial resistance of
      Salmonella spp. in shrimp samples from intensive and extensive farms located in
      three different provinces in the Mekong Delta, Vietnam. Shrimp from 11 of the 48
      farms all contained S. Weltevreden, except for one farm yielding S. Agona, with
      no difference in Salmonella occurrence between the two production systems. Pulsed
      field gel electrophoresis (PFGE) of S. Weltevreden showed closely related XbaI
      pulse types, suggesting a clonal relationship despite the farms and shrimp
      samples being epidemiologically unrelated. S. Weltevreden was susceptible to most
      antimicrobials tested, with a few strains being resistant to florfenicol,
      chloramphenicol, sulfamethoxazole or trimethoprim. Future studies of the ecology
      of S. Weltevreden should establish if this serovar may survive better and even
      multiply in warm-water shrimp farm environments compared to other Salmonella
      serovars. 

PMID- 26222548
TI  - Improvement of Endurance Based on Muscle Fiber-Type Composition by Treatment with
      Dietary Apple Polyphenols in Rats.
AB  - A recent study demonstrated a positive effect of apple polyphenol (APP) intake on
      muscle endurance of young-adult animals. While an enhancement of lipid metabolism
      may be responsible, in part, for the improvement, the contributing mechanisms
      still need clarification. Here we show that an 8-week intake of 5% (w/w) APP in
      the diet, up-regulates two features related to fiber type: the ratio of myosin
      heavy chain (MyHC) type IIx/IIb and myoglobin protein expression in plantaris
      muscle of 9-week-old male Fischer F344 rats compared to pair-fed controls (P <
      0.05). Results were demonstrated by our SDS-PAGE system specialized for MyHC
      isoform separation and western blotting of whole muscles. Animal-growth profiles
      (food intake, body-weight gain, and internal-organ weights) did not differ
      between the control and 5% APP-fed animals (n = 9/group). Findings may account
      for the increase in fatigue resistance of lower hind limb muscles, as evidenced
      by a slower decline in the maximum isometric planter-flexion torque generated by
      a 100-s train of electrical stimulation of the tibial nerve. Additionally, the
      fatigue resistance was lower after 8 weeks of a 0.5% APP diet than after 5% APP,
      supporting an APP-dose dependency of the shift in fiber-type composition.
      Therefore, the present study highlights a promising contribution of dietary APP
      intake to increasing endurance based on fiber-type composition in rat muscle.
      Results may help in developing a novel strategy for application in animal
      sciences, and human sports and age-related health sciences. 

PMID- 26222550
TI  - Competition in human groups-Impact on group cohesion, perceived stress and
      outcome satisfaction.
AB  - This study on competition in human groups was performed within the context of the
      competitive outcome interdependence concept: the degree to which personal
      outcomes among group members are affected by the consequences of task performance
      of others, e.g. when one group member gains a high reward for a task, this lowers
      the available reward for other group members. Our computer-based multi
      participant game empirically assessed how competitive versus neutral conditions
      influenced the reward-maximising behaviour of 200 undergraduate students
      functioning in ten-person groups - each playing two games (1 neutral and 1
      competitive), their perceived pay satisfaction as well as perceived stress levels
      and sense of calmness within the games' task to search for coins. Participants
      were represented by black dots moving on a virtual playground. Results showed
      that competition led to reward-maximising but fellow group member disadvantaging
      behaviour, and all participants experienced lower pay satisfaction, higher stress
      levels and less calmness. We conclude that short-term behavioural consequences of
      positive individual competitive behaviour were gained at the above-mentioned
      potential long-term negative costs for all group members. This implies group
      paradigms aimed at sustainability should avoid introducing competitive factors
      that at best result in short-lived gains and at worst cause widespread
      dissatisfaction, stress and a pervasive lack of calmness. 

PMID- 26222549
TI  - Multilevel Analysis of Trachomatous Trichiasis and Corneal Opacity in Nigeria:
      The Role of Environmental and Climatic Risk Factors on the Distribution of
      Disease.
AB  - The distribution of trachoma in Nigeria is spatially heterogeneous, with large
      scale trends observed across the country and more local variation within areas.
      Relative contributions of individual and cluster-level risk factors to the
      geographic distribution of disease remain largely unknown. The primary aim of
      this analysis is to assess the relationship between climatic factors and
      trachomatous trichiasis (TT) and/or corneal opacity (CO) due to trachoma in
      Nigeria, while accounting for the effects of individual risk factors and spatial
      correlation. In addition, we explore the relative importance of variation in the
      risk of trichiasis and/or corneal opacity (TT/CO) at different levels. Data from
      the 2007 National Blindness and Visual Impairment Survey were used for this
      analysis, which included a nationally representative sample of adults aged 40
      years and above. Complete data were available from 304 clusters selected using a
      multi-stage stratified cluster-random sampling strategy. All participants (13,543
      individuals) were interviewed and examined by an ophthalmologist for the presence
      or absence of TT and CO. In addition to field-collected data, remotely sensed
      climatic data were extracted for each cluster and used to fit Bayesian
      hierarchical logistic models to disease outcome. The risk of TT/CO was associated
      with factors at both the individual and cluster levels, with approximately 14% of
      the total variation attributed to the cluster level. Beyond established
      individual risk factors (age, gender and occupation), there was strong evidence
      that environmental/climatic factors at the cluster-level (lower precipitation,
      higher land surface temperature, higher mean annual temperature and rural
      classification) were also associated with a greater risk of TT/CO. This study
      establishes the importance of large-scale risk factors in the geographical
      distribution of TT/CO in Nigeria, supporting anecdotal evidence that
      environmental conditions are associated with increased risk in this context and
      highlighting their potential use in improving estimates of disease burden at
      large scales. 

PMID- 26222552
TI  - Stochastic optical reconstruction microscopy (STORM) in comparison with
      stimulated emission depletion (STED) and other imaging methods.
AB  - Stochastic optical reconstruction microscopy (STORM) and stimulated emission
      depletion (STED) microscopy are two super-resolution optical microscopy
      approaches that have rapidly gained popularity in recent years. Both modalities
      offer super-resolution imaging capabilities with the potential for imaging in
      multiple colors, three-dimensions, and the possibility to image in live cells. In
      this review, we focus on the specific advantages and disadvantages of each
      technique in the context of each other. STORM has been reported to achieve higher
      spatial resolution when compared to STED, but a lengthy acquisition may be
      required. STED utilizes relatively higher laser intensities, but is able to
      generate a super-resolution image immediately after acquisition without the need
      for any additional data processing. Ultimately, the choice between STORM and STED
      will depend not only on the specific application, but also on the users' ability
      to understand and optimize the various parameters ranging from sample preparation
      to image acquisition, which determine the quality of the final image. Stochastic
      optical reconstruction microscopy (STORM) and stimulated emission depletion
      (STED) are two super-resolution microscopy approaches that have rapidly gained
      popularity in recent years. STORM is based on the precise localization of a large
      number of individual molecules that together form a super-resolved image
      (bottom), whereas STED is based on the scanning of two super-imposed light
      sources which together allow for a super-resolved spot on the sample to be imaged
      (top). We discuss the specific advantages and disadvantages of each technique and
      explain the various parameters that affect image quality, which should be taken
      into consideration when planning experiments. 

PMID- 26222551
TI  - Altitudinal Barrier to the Spread of an Invasive Species: Could the Pyrenean
      Chain Slow the Natural Spread of the Pinewood Nematode?
AB  - Mountain ranges may delimit the distribution of native species as well as
      constitute potential barriers to the spread of invasive species. The invasive
      pinewood nematode, Bursaphelenchus xylophilus, is a severe forest pest inducing
      pine wilt disease. It is vectored in Europe by a native long-horned beetle,
      Monochamus galloprovincialis. This study explored the potential of the Pyrenean
      chain to slow or prevent the natural spread of nematode-infested beetles from the
      Iberian Peninsula, where the nematode is established and is expanding its range,
      towards France and the rest of Europe. An analysis of the genetic structure and
      migration patterns of the beetle populations throughout the Pyrenean mountain
      range was combined with a spread model simulating the potential movements of
      nematode-infested beetles across it. The central part of the Pyrenees, which
      corresponds to the highest elevation zone, was shown to prevent gene flow between
      the French and Spanish populations of M. galloprovincialis on each side of the
      mountains. Conversely, strong admixture was detected between populations located
      on both sides of low elevation hills, and especially at the east and west
      extremities of the mountain range. Simulations of the spread of nematode-infested
      beetles under various thresholds of beetle survival and pine wilt disease
      expression gave results consistent with the variation in genetic make-up,
      suggesting that western and eastern hillsides may represent corridors favoring
      natural spread of the nematode from the Iberian Peninsula to France. Simulations
      also showed that temperature rise due to climate change may significantly reduce
      the extent of the barrier formed by highest elevations. Our results support the
      hypothesis that the Pyrenean chain represents a partial barrier to the natural
      spread of nematode-infested beetles. These results, which have to be considered
      together with potential human-assisted long-distance spread of the nematode,
      highlight priority zones for future pest monitoring and management programs. More
      generally, such an integrated approach could be used to assess the role of
      mountain chains in the potential spread of other invasive pests. 

PMID- 26222554
TI  - Long Frontal Projections Help Battus philenor (Lepidoptera: Papilionidae) Larvae
      Find Host Plants.
AB  - Animals sometimes develop conspicuous projections on or near their heads as,
      e.g., weaponry, burrowing or digging tools, and probes to search for resources.
      The frontal projections that insects generally use to locate and assess resources
      are segmented appendages, including antennae, maxillary palps, and labial palps.
      There is no evidence to date that arthropods, including insects, use projections
      other than true segmental appendages to locate food. In this regard, it is
      noteworthy that some butterfly larvae possess a pair of long antenna-like
      projections on or near their heads. To date, the function of these projections
      has not been established. Larvae of pipevine swallowtail butterflies Battus
      philenor (Papilionidae) have a pair of long frontal fleshy projections that, like
      insect antennae generally, can be actively moved. In this study, we evaluated the
      possible function of this pair of long moveable frontal projections. In
      laboratory assays, both frontal projections and lateral ocelli were shown to
      increase the frequency with which search larvae found plants. The frontal
      projections increased finding of host and non-host plants equally, suggesting
      that frontal projections do not detect host-specific chemical cues. Detailed SEM
      study showed that putative mechanosensillae are distributed all around the
      frontal as well as other projections. Taken together, our findings suggest that
      the frontal projections and associated mechanosensillae act as vertical object
      detectors to obtain tactile information that, together with visual information
      from lateral ocelli and presumably chemical information from antennae and
      mouthparts, help larvae to find host plants. Field observations indicate that
      host plants are small and scattered in southern Arizona locations. Larvae must
      therefore find multiple host plants to complete development and face significant
      challenges in doing so. The frontal projections may thus be an adaptation for
      finding a scarce resource before starving to death. This is the first evidence
      that arthropods use projections other than true segmental appendages such as
      antennae, mouthparts and legs, to locate food resources. 

PMID- 26222553
TI  - Expression of MYCN in Multipotent Sympathoadrenal Progenitors Induces
      Proliferation and Neural Differentiation, but Is Not Sufficient for
      Tumorigenesis.
AB  - Neuroblastoma is a pediatric malignancy of the sympathetic ganglia and adrenal
      glands, hypothesized to originate from progenitors of the developing sympathetic
      nervous system. Amplification of the MYCN oncogene is a genetic marker of risk in
      this disease. Understanding the impact of oncogene expression on sympathoadrenal
      progenitor development may improve our knowledge of neuroblastoma initiation and
      progression. We isolated sympathoadrenal progenitor cells from the postnatal
      murine adrenal gland by sphere culture and found them to be multipotent,
      generating differentiated colonies of neurons, Schwann cells, and myofibroblasts.
      MYCN overexpression in spheres promoted commitment to the neural lineage,
      evidenced by an increased frequency of neuron-containing colonies. MYCN promoted
      proliferation of both sympathoadrenal progenitor spheres and differentiated
      neurons derived from these spheres, but there was also an increase in apoptosis.
      The proliferation, apoptosis, and neural lineage commitment induced by MYCN are
      tumor-like characteristics and thereby support the hypothesis that multipotent
      adrenal medullary progenitor cells are cells of origin for neuroblastoma. We
      find, however, that MYCN overexpression is not sufficient for these cells to form
      tumors in nude mice, suggesting that additional transforming mutations are
      necessary for tumorigenesis. 

PMID- 26222555
TI  - The Older Americans Act at 50--Community-Based Care in a Value-Driven Era.

PMID- 26222556
TI  - Structural Approaches to Cancer Drug Development.

PMID- 26222557
TI  - Therapeutic Hypothermia in Deceased Organ Donors and Kidney-Graft Function.
AB  - BACKGROUND: Delayed graft function, which is reported in up to 50% of kidney
      transplant recipients, is associated with increased costs and diminished long
      term graft function. The effect that targeted mild hypothermia in organ donors
      before organ recovery has on the rate of delayed graft function is unclear.
      METHODS: We enrolled organ donors (after declaration of death according to
      neurologic criteria) from two large donation service areas and randomly assigned
      them to one of two targeted temperature ranges: 34 to 35 degrees C (hypothermia)
      or 36.5 to 37.5 degrees C (normothermia). Temperature protocols, which were
      initiated after authorization was obtained for the organ to be donated and for
      the donor's participation in the study, ended when organ donors left the
      intensive care unit for organ recovery in the operating room. The primary outcome
      was delayed graft function in the kidney recipients, which was defined as the
      requirement for dialysis during the first week after transplantation. Secondary
      outcomes were the rates of individual organs transplanted in each treatment group
      and the total number of organs transplanted from each donor. RESULTS: The study
      was terminated early, on the recommendation of an independent data and safety
      monitoring board, after the interim analysis showed efficacy of hypothermia. At
      trial termination, 370 organ donors had been enrolled (180 in the hypothermia
      group and 190 in the normothermia group). A total of 572 patients received a
      kidney transplant (285 kidneys from donors in the hypothermia group and 287
      kidneys from donors in the normothermia group). Delayed graft function developed
      in 79 recipients of kidneys from donors in the hypothermia group (28%) and in 112
      recipients of kidneys from donors in the normothermia group (39%) (odds ratio,
      0.62; 95% confidence interval, 0.43 to 0.92; P=0.02). CONCLUSIONS: Mild
      hypothermia, as compared with normothermia, in organ donors after declaration of
      death according to neurologic criteria significantly reduced the rate of delayed
      graft function among recipients. (Funded by the Health Resources and Services
      Administration; ClinicalTrials.gov number, NCT01680744.).

PMID- 26222558
TI  - Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor.
AB  - BACKGROUND: Expression of the colony-stimulating factor 1 (CSF1) gene is elevated
      in most tenosynovial giant-cell tumors. This observation has led to the discovery
      and clinical development of therapy targeting the CSF1 receptor (CSF1R). METHODS:
      Using x-ray co-crystallography to guide our drug-discovery research, we generated
      a potent, selective CSF1R inhibitor, PLX3397, that traps the kinase in the
      autoinhibited conformation. We then conducted a multicenter, phase 1 trial in two
      parts to analyze this compound. In the first part, we evaluated escalations in
      the dose of PLX3397 that was administered orally in patients with solid tumors
      (dose-escalation study). In the second part, we evaluated PLX3397 at the chosen
      phase 2 dose in an extension cohort of patients with tenosynovial giant-cell
      tumors (extension study). Pharmacokinetic and tumor responses in the enrolled
      patients were assessed, and CSF1 in situ hybridization was performed to confirm
      the mechanism of action of PLX3397 and that the pattern of CSF1 expression was
      consistent with the pathological features of tenosynovial giant-cell tumor.
      RESULTS: A total of 41 patients were enrolled in the dose-escalation study, and
      an additional 23 patients were enrolled in the extension study. The chosen phase
      2 dose of PLX3397 was 1000 mg per day. In the extension study, 12 patients with
      tenosynovial giant-cell tumors had a partial response and 7 patients had stable
      disease. Responses usually occurred within the first 4 months of treatment, and
      the median duration of response exceeded 8 months. The most common adverse events
      included fatigue, change in hair color, nausea, dysgeusia, and periorbital edema;
      adverse events rarely led to discontinuation of treatment. CONCLUSIONS: Treatment
      of tenosynovial giant-cell tumors with PLX3397 resulted in a prolonged regression
      in tumor volume in most patients. (Funded by Plexxikon; ClinicalTrials.gov
      number, NCT01004861.).

PMID- 26222559
TI  - Antisense Inhibition of Apolipoprotein C-III in Patients with
      Hypertriglyceridemia.
AB  - BACKGROUND: Apolipoprotein C-III (APOC3) is a key regulator of plasma
      triglyceride levels. Elevated triglyceride levels are associated with a risk of
      adverse cardiovascular events and pancreatitis. ISIS 304801 is a second
      generation antisense inhibitor of APOC3 synthesis. METHODS: We conducted a
      randomized, double-blind, placebo-controlled, dose-ranging, phase 2 study to
      evaluate ISIS 304801 in untreated patients with fasting triglyceride levels
      between 350 mg per deciliter (4.0 mmol per liter) and 2000 mg per deciliter (22.6
      mmol per liter) (ISIS 304801 monotherapy cohort), as well as in patients
      receiving stable fibrate therapy who had fasting triglyceride levels between 225
      mg per deciliter (2.5 mmol per liter) and 2000 mg per deciliter (ISIS 304801
      fibrate cohort). Eligible patients were randomly assigned to receive either ISIS
      304801, at doses ranging from 100 to 300 mg, or placebo, once weekly for 13
      weeks. The primary outcome was the percentage change in APOC3 level from
      baseline. RESULTS: A total of 57 patients were treated in the ISIS 304801
      monotherapy cohort (41 received active agent, and 16 received placebo), and 28
      patients were treated in the ISIS 304801-fibrate cohort (20 received active
      agent, and 8 received placebo). The mean (+/-SD) baseline triglyceride levels in
      the two cohorts were 581+/-291 mg per deciliter (6.6+/-3.3 mmol per liter) and
      376+/-188 mg per deciliter (4.2+/-2.1 mmol per liter), respectively. Treatment
      with ISIS 304801 resulted in dose-dependent and prolonged decreases in plasma
      APOC3 levels when the drug was administered as a single agent (decreases of
      40.0+/-32.0% in the 100-mg group, 63.8+/-22.3% in the 200-mg group, and 79.6+/
      9.3% in the 300-mg group, vs. an increase of 4.2+/-41.7% in the placebo group)
      and when it was administered as an add-on to fibrates (decreases of 60.2+/-12.5%
      in the 200-mg group and 70.9+/-13.0% in the 300-mg group, vs. a decrease of 2.2+/
      25.2% in the placebo group). Concordant reductions of 31.3 to 70.9% were observed
      in triglyceride levels. No safety concerns were identified in this short-term
      study. CONCLUSIONS: We found that treatment with ISIS 304801 was associated with
      significant lowering of triglyceride levels, among patients with a broad range of
      baseline levels, through selective antisense inhibition of APOC3 synthesis.
      (Funded by Isis Pharmaceuticals; ClinicalTrials.gov number, NCT01529424.).

PMID- 26222561
TI  - Chagas' Disease.

PMID- 26222560
TI  - Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer.
AB  - Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid
      cancer, but the susceptibility genes are not known. Here, we report a germline
      variant of HABP2 in seven affected members of a kindred with familial
      nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This
      variant was associated with increased HABP2 protein expression in tumor samples
      from affected family members, as compared with normal adjacent thyroid tissue and
      samples from sporadic cancers. Functional studies showed that HABP2 has a tumor
      suppressive effect, whereas the G534E variant results in loss of function. 

PMID- 26222562
TI  - IMAGES IN CLINICAL MEDICINE. Strawberry Tongue.

PMID- 26222563
TI  - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 24-2015. A 28-Year-Old
      Pregnant Woman with Fever, Chills, Headache, and Fatigue.

PMID- 26222564
TI  - Taking the Heat Out of Organ Donation.

PMID- 26222566
TI  - Targeting the Effect of VEGF in Diabetic Macular Edema.

PMID- 26222565
TI  - Targeting the Effect of VEGF in Diabetic Macular Edema.

PMID- 26222567
TI  - Targeting the Effect of VEGF in Diabetic Macular Edema.

PMID- 26222568
TI  - Targeting the Effect of VEGF in Diabetic Macular Edema.

PMID- 26222569
TI  - Targeting the Effect of VEGF in Diabetic Macular Edema.

PMID- 26222570
TI  - Surgical Ablation for Atrial Fibrillation.

PMID- 26222571
TI  - Surgical Ablation for Atrial Fibrillation.

PMID- 26222572
TI  - Surgical Ablation for Atrial Fibrillation.

PMID- 26222573
TI  - Iron-Deficiency Anemia.

PMID- 26222574
TI  - Iron-Deficiency Anemia.

PMID- 26222575
TI  - Iron-Deficiency Anemia.

PMID- 26222576
TI  - Case 9-2015: A Man with Personality Changes and Progressive Neurologic Decline.

PMID- 26222577
TI  - Case 9-2015: A Man with Personality Changes and Progressive Neurologic Decline.

PMID- 26222578
TI  - Human Infection with a Novel Avian Influenza A(H5N6) Virus.

PMID- 26222579
TI  - U.S.-Citizen International Medical Graduates.

PMID- 26222580
TI  - U.S.-Citizen International Medical Graduates.

PMID- 26222581
TI  - IMAGES IN CLINICAL MEDICINE. Squamous-Cell Carcinoma Resembling Pyoderma
      Gangrenosum.

PMID- 26222582
TI  - Allelic diversity for neutral markers retains a higher adaptive potential for
      quantitative traits than expected heterozygosity.
AB  - The adaptive potential of a population depends on the amount of additive genetic
      variance for quantitative traits of evolutionary importance. This variance is a
      direct function of the expected frequency of heterozygotes for the loci which
      affect the trait (QTL). It has been argued, but not demonstrated experimentally,
      that long-term response to selection is more dependent on QTL allelic diversity
      than on QTL heterozygosity. Conservation programmes, aimed at preserving this
      variation, usually rely on neutral markers rather than on quantitative traits for
      making decisions on management. Here, we address, both through simulation
      analyses and experimental studies with Drosophila melanogaster, the question of
      whether allelic diversity for neutral markers is a better indicator of a high
      adaptive potential than expected heterozygosity. In both experimental and
      simulation studies, we established synthetic populations for which either
      heterozygosity or allelic diversity was maximized using information from QTL
      (simulations) or unlinked neutral markers (simulations and experiment). The
      synthetic populations were selected for the quantitative trait to evaluate the
      evolutionary potential provided by the two optimization methods. Our results show
      that maximizing the number of alleles of a low number of markers implies higher
      responses to selection than maximizing their heterozygosity. 

PMID- 26222583
TI  - Assessing the Genetics Content in the Next Generation Science Standards.
AB  - Science standards have a long history in the United States and currently form the
      backbone of efforts to improve primary and secondary education in science,
      technology, engineering, and math (STEM). Although there has been much political
      controversy over the influence of standards on teacher autonomy and student
      performance, little light has been shed on how well standards cover science
      content. We assessed the coverage of genetics content in the Next Generation
      Science Standards (NGSS) using a consensus list of American Society of Human
      Genetics (ASHG) core concepts. We also compared the NGSS against state science
      standards. Our goals were to assess the potential of the new standards to support
      genetic literacy and to determine if they improve the coverage of genetics
      concepts relative to state standards. We found that expert reviewers cannot
      identify ASHG core concepts within the new standards with high reliability,
      suggesting that the scope of content addressed by the standards may be
      inconsistently interpreted. Given results that indicate that the disciplinary
      core ideas (DCIs) included in the NGSS documents produced by Achieve, Inc.
      clarify the content covered by the standards statements themselves, we recommend
      that the NGSS standards statements always be viewed alongside their supporting
      disciplinary core ideas. In addition, gaps exist in the coverage of essential
      genetics concepts, most worryingly concepts dealing with patterns of inheritance,
      both Mendelian and complex. Finally, state standards vary widely in their
      coverage of genetics concepts when compared with the NGSS. On average, however,
      the NGSS support genetic literacy better than extant state standards. 

PMID- 26222585
TI  - Anti-inflammatory, antioxidant and antiangiogenic activities of diosgenin
      isolated from traditional medicinal plant, Costus speciosus (Koen ex.Retz.) Sm.
AB  - Costus speciosus is an important medicinal plant widely used in several
      indigenous medicinal formulations. The present study was conducted to evaluate
      the in vitro anti-inflammatory, antioxidant and antiangiogenic activities of
      diosgenin isolated from C. speciosus. The diosgenin was isolated from C.
      speciosus by HPTLC and its biological activities were studied by different
      protocols. The results demonstrated that LPS stimulated TNF-alpha generation in
      RAW 264.7 macrophage culture supernatant up to 3.7-fold of the control and that
      sample treatment (50 MUg/mL) resulted in a highly significant inhibitory effect
      on LPS-stimulated TNF-alpha (p < 0.01) in a similar manner to methotrexate
      inhibitory effect. The tested sample possessed an effective antioxidant
      scavenging affinity against DPPH radicals as compared with the standard
      antioxidant activity of vitamin C. The results presented here may suggest that
      diosgenin isolated from C. speciosus possess anticancer, apoptotic and inhibitory
      effects on cell proliferation. 

PMID- 26222586
TI  - Three Series of Sulfo-Functionalized Mixed-Linker CAU-10 Analogues: Sorption
      Properties, Proton Conductivity, and Catalytic Activity.
AB  - Ten mixed-linker metal-organic frameworks [Al(OH)(m-BDC-X)(1-y)(m-BDC-SO3H)y]
      (H2BDC = 1,3-benzenedicarboxylic acid; X = H, NO2, OH) exhibiting the CAU-10-type
      structure were synthesized. The compounds can be grouped into three series
      according to the combination of ligands employed. The three series of compounds
      were obtained by employing different ratios of m-H2 BDC-X and m-H2BDC-SO3Li. The
      resulting compounds, which are denoted CAU-10-H/Sx, -N/Sx and -O/Sx, show
      exceptionally high thermal stability for sulfonated materials of up to 350 
      degrees C. Detailed characterization with special focus on polarity and acidity
      was performed, and the impact of the additional SO3H groups is clearly
      demonstrated by changes in the sorption affinities/capacities towards several
      gases and water vapor. In addition, selected samples were evaluated for proton
      conductivity and as catalysts for the gas-phase dehydration of ethanol to
      ethylene. While only very low proton conductivities were observed, a pronounced
      increase in catalytic activity was achieved. Although reactions were performed at
      temperatures of 250 and 300  degrees C for more than 40 h, no desulfonation and
      no loss of crystallinity were observed, and stable ethanol conversion resulted.
      This demonstrates the high stability of this material.

PMID- 26222584
TI  - Expanding the Described Metabolome of the Marine Cyanobacterium Moorea producens
      JHB through Orthogonal Natural Products Workflows.
AB  - Moorea producens JHB, a Jamaican strain of tropical filamentous marine
      cyanobacteria, has been extensively studied by traditional natural products
      techniques. These previous bioassay and structure guided isolations led to the
      discovery of two exciting classes of natural products, hectochlorin (1) and
      jamaicamides A (2) and B (3). In the current study, mass spectrometry-based
      'molecular networking' was used to visualize the metabolome of Moorea producens
      JHB, and both guided and enhanced the isolation workflow, revealing additional
      metabolites in these compound classes. Further, we developed additional insight
      into the metabolic capabilities of this strain by genome sequencing analysis,
      which subsequently led to the isolation of a compound unrelated to the
      jamaicamide and hectochlorin families. Another approach involved stimulation of
      the biosynthesis of a minor jamaicamide metabolite by cultivation in modified
      media, and provided insights about the underlying biosynthetic machinery as well
      as preliminary structure-activity information within this structure class. This
      study demonstrated that these orthogonal approaches are complementary and enrich
      secondary metabolomic coverage even in an extensively studied bacterial strain.

PMID- 26222587
TI  - Gamma heavy chain disease associated with large granular lymphocytic leukemia: A
      report of two cases and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Gamma heavy chain diseases (gammaHCD) and large
      granular lymphocyte (LGL) leukemia are two rare lymphoproliferative diseases,
      respectively with B and T phenotype. Both gammaHCD and LGL leukemia share some
      similar clinical features, such as cytopenias, splenomegaly, and recurrent
      infections. Association of these two diseases is exceptional and suggest
      pathogenic link. We report two cases of gammaHCD associated with T-LGL leukemia.
      CLINICAL PRESENTATION: Patient 1 was a 70-year-old woman, with lymphoplasmacytic
      lymphoma, refractory to chlorambucil-rituximab treatment. She developed during
      the follow up a gammaHCD with T-LGL leukemia, unresponsive to melphalan,
      thalidomide, and steroids, requiring supportive care. Patient 2 was a 40-year-old
      man with chronic severe asymptomatic neutropenia, revealing both gammaHCD and T
      LGL leukemia. He is still well without any treatment nor complications, with 7
      years follow up. CONCLUSION: Several types of B lymphoproliferative disease are
      associated with LGL leukemia. Although exceptional, this association of two rare
      lymphoproliferative disorders, with a different phenotype, does not seem
      fortuitous.

PMID- 26222588
TI  - Advances in the biomedical application of polymer-functionalized carbon
      nanotubes.
AB  - Nowadays, carbon nanotubes (CNTs) have attracted the attention of scientists
      because of their unique electronic, magnetic, optical, mechanical, and chemical
      properties. However, their poor solubility in solvents, especially in water,
      limits their applications in several promising fields such as biomedicine,
      biomedical imaging, and cancer therapy. The attachment of hydrophilic segments to
      CNTs is a very efficient method for overcoming this problem. This review covers
      the latest advances in the synthesis of water-soluble CNTs with an emphasis on
      the molecular structure of various categories of hydrophilic
      molecules/macromolecules which have been grafted onto the surface of CNTs.
      Indeed, from the viewpoint of chemical synthesis, covalent bonding of several
      water-soluble molecules/macromolecules including small water-soluble organic
      molecules, linear, hyperbranched and dendritic polymers/biopolymers,
      glycoconjugate molecules/polymers as well as biomolecules onto the surface of
      CNTs has been deeply surveyed. Moreover, the most recent and interesting bio
      applications of polymer-functionalized water-soluble CNTs have been properly
      reviewed. 

PMID- 26222589
TI  - Structural and functional changes in high-density lipoprotein induced by chemical
      modification.
AB  - Reconstituted high-density lipoprotein (rHDL), a natural nanoparticle consisting
      of apolipoprotein A-I and phospholipids, was modified with a hydrophobic
      fluorescent dye before (pre-rHDL) and after (post-rHDL) reconstitution. Pre-rHDL
      particles had a similar size to unmodified rHDL, but post-rHDL particles were
      significantly larger and their avidity for a HDL receptor was 2.6 times of that
      shown by pre-rHDL. 

PMID- 26222590
TI  - MNAzyme-catalyzed nucleic acid detection enhanced by a cationic copolymer.
AB  - Multi-component nucleotide acid enzymes (MNAzymes) derived from RNase-mimic
      DNAzymes have potential as simple and accurate DNA detectors. To enhance the
      MNAzyme activity under multiple-turnover conditions, a cationic comb-type
      copolymer, PLL-g-Dex, that facilitates hybridization and strand exchange
      reactions of DNA was utilized. The copolymer increased the MNAzyme reaction rate
      by 200 times, allowing target DNA detection at picomolar concentrations at
      physiological temperature. 

PMID- 26222591
TI  - Facile synthesis of RGD peptide-modified iron oxide nanoparticles with ultrahigh
      relaxivity for targeted MR imaging of tumors.
AB  - We report the facile synthesis of arginine-glycine-aspartic acid (RGD) peptide
      targeted iron oxide (Fe3O4) nanoparticles (NPs) with ultrahigh relaxivity for in
      vivo tumor magnetic resonance (MR) imaging. In this study, stable
      polyethyleneimine (PEI)-coated Fe3O4 NPs were first prepared by a mild reduction
      route. The formed aminated Fe3O4 NPs with PEI coating were sequentially
      conjugated with fluorescein isothiocyanate (FI) and polyethylene glycol (PEG)-RGD
      segment, followed by acetylation of the remaining PEI surface amines. The thus
      formed Fe3O4@PEI.NHAc-FI-PEG-RGD NPs were characterized via different techniques.
      We show that the multifunctional RGD-targeted Fe3O4 NPs with a mean size of 9.1
      nm are water-dispersible, colloidally stable, and hemocompatible and
      cytocompatible in the given concentration range. With the displayed ultrahigh r2
      relaxivity (550.04 mM(-1) s(-1)) and RGD-mediated targeting specificity to
      alphavbeta3 integrin-overexpressing cancer cells as confirmed by flow cytometry
      and confocal microscopy, the developed multifunctional Fe3O4@PEI.NHAc-FI-PEG-RGD
      NPs are able to be used as a highly efficient nanoprobe for targeted MR imaging
      of alphavbeta3 integrin-overexpressing cancer cells in vitro and the xenografted
      tumor model in vivo. Given the versatile PEI amine-enabled conjugation chemistry,
      the developed PEI-coated Fe3O4 NPs may be functionalized with other biological
      ligands or drugs for various biomedical applications, in particular, the
      diagnosis and therapy of different types of cancer. 

PMID- 26222592
TI  - Nanoparticles for inhibition of in vitro tumour angiogenesis: synergistic actions
      of ligand function and laser irradiation.
AB  - Careful design of nanoparticles plays a crucial role in their biomedical
      applications. It not only defines the stability of nanoparticles in a biological
      medium but also programs their biological functionality and specific interactions
      with cells. Here, an inorganic nanoparticulate system engineered to have a dual
      role as anti-angiogenic and hyperthermic agent is presented. The inorganic rod
      shaped core is designed to strongly absorb near-infrared laser irradiation
      through the surface plasmon resonance and convert it into localized heat, while a
      peptide coating acts as an anti-angiogenic drug, altogether inhibiting vascular
      growth. The synergistic dual action provides an improved inhibition of the in
      vitro tumour angiogenesis, offering new possibilities for the development of nano
      engineered anti-angiogenic drugs for therapies. 

PMID- 26222593
TI  - Covalently conjugated transforming growth factor-beta1 in modular chitosan
      hydrogels for the effective treatment of articular cartilage defects.
AB  - Approaches to control precisely growth factor presentation to a tissue defect in
      a sustained fashion are of increasing interest for a number of complex tissue
      engineering applications. Although transforming growth factor beta-1 (TGF-beta1)
      plays a key role in promoting chondrogenesis, the therapeutic use of TGF-beta1 is
      limited by its inherent protein instability, requiring high amounts of the
      protein that can cause adverse side effects with inefficient cartilage formation.
      In this work, we have developed strategies to stabilize TGF-beta1 signaling in
      the injectable, visible blue light inducible chitosan (MeGC) hydrogel system for
      specific use in cartilage regeneration. We successfully modulated delivery of TGF
      beta1 with reduced burst release in a complex biological environment of serum and
      cells by covalently conjugating the protein to MeGC hydrogels with preserving
      type II collagen, one of the major cartilaginous extracellular matrix (ECM)
      components. The hydrogel system supported cellular condensation and deposition of
      cartilaginous ECM by encapsulating adipose derived stem cells in vitro. We
      confirmed further the ability of these TGF-beta1 functionalized hydrogel systems
      to promote cartilage regeneration in challenging healing environments such as in
      a rat partial-thickness chondral defect model which present a limited source of
      subchondral bone marrow elements. These results suggest a new injectable delivery
      modality of therapeutic agents to improve clinical cartilage repair. 

PMID- 26222594
TI  - Co-delivery of proapoptotic peptide and p53 DNA by reduction-sensitive
      polypeptides for cancer therapy.
AB  - In order to produce a more efficient cancer cell death, a dual-functional
      polypeptide, xPolyR8-KLA(TPP), was synthesized by disulfide cross-linking CR8C
      and C-KLA(TPP). The obtained xPolyR8-KLA(TPP) could not only initiate tumor cell
      apoptosis by C-KLA(TPP) with improved cell penetrating ability, but was also
      capable of loading and delivering the tumor cell suppressing p53 gene. It was
      found that, after internalization by cancer cells, the xPolyR8-KLA(TPP)/p53
      complex released the C-KLA(TPP) moiety and the p53 gene in the cytoplasm due to
      its reducible disulfide bonds. By regulating both the intrinsic and extrinsic
      apoptotic pathways, the xPolyR8-KLA(TPP)/p53 complex performed as a synergetic
      system and lead to a more efficient cancer cell death. 

PMID- 26222595
TI  - Gene expression of ternary complexes through the compaction of nanofiber
      polyplexes by mixing with lipofectamine.
AB  - For the development of an effective nonviral gene vector, ternary complexes were
      prepared through the compaction of nanofiber-polyplexes. These were formed using
      pDNA and a head-tail type polycation bearing a multi-arm poly(ethylene glycol)
      head and a poly(l-lysine) tail, and this strategy was based on the crowding
      effect of poly(ethylene glycol) in the polyplex. Mixing was carried out using a
      cationic lipid (lipofectamine), which is a commercially available transfection
      reagent. Through ternary complex formation, the elongated morphology of nanofiber
      polyplexes was found to compact into a spherical shape with an average diameter
      of ca. 100 nm. Accompanying ternary complex formation, the compaction of the
      nanofiber-polyplexes can improve cellular uptake and helps the ternary complex to
      retain its smooth transcription/translation process, which is characteristic of
      nanofiber-polyplexes. As a result, ternary complexes prepared at an optimal
      mixing ratio exhibit a high transfection efficiency compared with lipofectamine
      lipoplexes. 

PMID- 26222596
TI  - Antimicrobial peptide LL-37 on surfaces presenting carboxylate anions.
AB  - Antimicrobial peptides (AMPs) are part of the immune system in a wide range of
      organisms. They generally carry positive charges under physiological conditions,
      allowing them to accumulate on the negatively charged bacterial membrane as the
      first step of bactericidal action. The concentration range of AMPs necessary for
      rapid killing of bacteria tested in vitro is much higher than levels found at
      epithelial surfaces and body fluids in vivo, and close to the a level that is
      toxic to the host cells. It is likely that AMPs in vivo are localized and act
      cooperatively to enhance antimicrobial activity, while the global concentration
      is low thus demonstrating low toxicity to host cells. Herein we employed well
      defined mixed self-assembled monolayers (SAMs) to localize LL-37, one of the most
      studied AMPs, via electrostatic interactions. We systematically varied the
      surface density of LL-37, and found that the immobilized AMPs not only attracted
      bacteria Pseudomonas aeruginosa to the surface, but also killed nearly all
      bacteria when above a threshold density. More significantly, the AMPs displayed
      low toxicity to human corneal epithelial cells. The results indicated that
      localization of AMPs on suitable polyanion substrates facilitated the
      bactericidal activity while minimizing the cytotoxicity of AMPs. 

PMID- 26222597
TI  - Deaths: Final Data for 2011.
AB  - OBJECTIVES: This report presents final 2011 data on U.S. deaths, death rates,
      life expectancy, infant mortality, and trends by selected characteristics such as
      age, sex, Hispanic origin, race, state of residence, and cause of death. METHODS:
      Information reported on death certificates, which is completed by funeral
      directors, attending physicians, medical examiners, and coroners, is presented in
      descriptive tabulations. The original records are filed in state registration
      offices. Statistical information is compiled in a national database through the
      Vital Statistics Cooperative Program of the Centers for Disease Control and
      Prevention's National Center for Health Statistics. Causes of death are processed
      in accordance with the International Classification of Diseases, Tenth Revision.
      RESULTS: In 2011, a total of 2,515,458 deaths were reported in the United States.
      The age-adjusted death rate was 741.3 deaths per 100,000 standard population, a
      decrease of 0.8% from the 2010 rate and a record low figure. Life expectancy at
      birth in 2011 was unchanged from 2010 at 78.7 years. Age-specific death rates
      decreased in 2011 from 2010 for age groups under 1 year, 65-74, 75-84, and 85 and
      over. Age-specific death rates increased for age groups 25-34 and 45-54. The
      leading causes of death in 2011 remained the same as in 2010, although two causes
      exchanged ranks. Kidney disease, the eighth leading cause in 2010, became the
      ninth leading cause in 2011, while Influenza and pneumonia, the ninth leading
      cause in 2010, became the eighth leading cause of death in 2011. The infant
      mortality rate of 6.07 deaths per 1,000 live births in 2011 was a historically
      low value. CONCLUSION: The decline of the age-adjusted death rate to a record low
      value for the United States is consistent with long-term trends in mortality.

PMID- 26222598
TI  - How to Receive More Funding for Your Research? Get Connected to the Right People!
AB  - Funding has been viewed in the literature as one of the main determinants of
      scientific activities. Also, at an individual level, securing funding is one of
      the most important factors for a researcher, enabling him/her to carry out
      research projects. However, not everyone is successful in obtaining the necessary
      funds. The main objective of this work is to measure the effect of several
      important factors such as past productivity, scientific collaboration or career
      age of researchers, on the amount of funding that is allocated to them. For this
      purpose, the paper estimates a temporal non-linear multiple regression model.
      According to the results, although past productivity of researchers positively
      affects the funding level, our findings highlight the significant role of
      networking and collaboration. It was observed that being a member of large
      scientific teams and getting connected to productive researchers who have also a
      good control over the collaboration network and the flow of information can
      increase the chances for securing more money. In fact, our results show that in
      the quest for the research money it is more important how researchers build their
      collaboration network than what publications they produce and whether they are
      cited. 

PMID- 26222599
TI  - Collision-energy resolved ion mobility characterization of isomeric mixtures.
AB  - Existing instrumental resolving power limitations in ion mobility spectrometry
      (IMS) often restrict adequate characterization of unresolved or co-eluting
      chemical isomers. Recently, we introduced a novel chemometric deconvolution
      approach that utilized post-IM collision-induced dissociation (CID) mass
      spectrometry (MS) data to extract "pure" IM profiles and construct CID mass
      spectra of individual components from a mixture containing two IM-overlapped
      components [J. Am. Soc. Mass Spectrom., 2012, 23, 1873-1884]. In this manuscript
      we extend the capabilities of the IM-MS deconvolution methodology and demonstrate
      the utility of energy resolved IM deconvolution for successful characterization
      of ternary and quaternary isomer mixtures with overlapping IM profiles.
      Furthermore, we show that the success of IM-MS deconvolution is a collision
      energy dependent process where different isomers can be identified at various ion
      fragmentation collision-energies. Details on how to identify a single collision
      energy or suitable collision-energy ranges for successful characterization of
      isomer mixtures are discussed. To confirm the validity of the proposed approach,
      deconvoluted IM and MS spectra from IM overlapped analyte mixtures are compared
      to IM and MS data from individually run mixture components. Criteria for
      "successful" deconvolution of overlapping IM profiles and extraction of their
      corresponding pure mass spectra are discussed. 

PMID- 26222600
TI  - Correction: Fish Farms at Sea: The Ground Truth from Google Earth.

PMID- 26222601
TI  - Infrared and Raman Spectroscopy from Ab Initio Molecular Dynamics and Static
      Normal Mode Analysis: The C-H Region of DMSO as a Case Study.
AB  - Carbon-hydrogen (C-H) vibration modes serve as key probes in the chemical
      identification of hydrocarbons and in vibrational sum-frequency generation
      spectroscopy of hydrocarbons at the liquid/gas interface. Their assignments pose
      a challenge from a theoretical viewpoint. In this work, we present a detailed
      study of the C-H stretching region of dimethyl sulfoxide using a new ab initio
      molecular dynamics (AIMD) module that we have implemented in NWChem. Through a
      combination of AIMD simulations and static normal mode analysis, we interpret
      experimental infrared and Raman spectra and explore the role of anharmonic
      effects in this system. Comprehensive anharmonic normal mode analysis of the C-H
      stretching region casts doubt upon previous experimental assignments of the
      shoulder on the symmetric C-H stretching peak. In addition, our AIMD simulations
      also show significant broadening of the in-phase symmetric C-H stretching
      resonance, which suggests that the experimentally observed shoulder is due to
      thermal broadening of the symmetric stretching resonance. 

PMID- 26222602
TI  - Use of solar distillation for olive mill wastewater drying and recovery of
      polyphenolic compounds.
AB  - Olive mill wastewater (OMW) is characterized by its high organic load and the
      presence of phenolic compounds. For first time, a solar distillator was used to
      investigate the simultaneous solar drying of OMW and the recovery of phenolic
      compounds with antioxidant properties in the distillate. Two experiments were
      conducted and the role of thermal insulation on the performance of the distiller
      was studied. The use of insulation resulted to higher temperatures in the
      distillator (up to 84.3  degrees C and 78.5  degrees C at the air and sludge,
      respectively), shorter period for OMW dewatering (14 days), while it increased
      the performance of distillator by 26.1%. Chemical characterization of the
      distillate showed that pH and COD concentration gradually decreased during the
      experiments, whereas an opposite trend was noticed for conductivity and total
      phenols concentration. Almost 4% of the total phenols found initially in OMW were
      transferred to the distillate when an insulated solar distillator was used. Gas
      chromatographic analysis of collected distillates confirmed the presence of
      tyrosol in all samples; whereas hydroxytyrosol was found only in fresh collected
      distillate samples. Further experiments should be conducted to optimize the
      process and quantify the concentrations of recovered phenolic compounds. 

PMID- 26222603
TI  - Quantification of the perceived training load and its relationship with changes
      in physical fitness performance in junior soccer players.
AB  - The aim of this study was to determine the relationship between perceived
      respiratory and muscular training load (TL) and changes in physical fitness in
      elite and non-elite junior soccer players. Twenty-eight elite (n = 14, 17.6 +/-
      0.6 years, 70.3 +/- 4.4 kg, 179.7 +/- 5.6 cm) and non-elite (n = 14, 17.5 +/- 0.5
      years, 71.1 +/- 6.5 kg, 178.1 +/- 5.6 cm) soccer players belonging to a Spanish
      first and third division football academies and competing in junior Spanish first
      division (2012-2013) participated in the study. Countermovement jump (CMJ), CMJ
      arm swing, 5 and 15 m sprints and the Universite de Montreal endurance test were
      performed in January and 9 weeks later in March. In order to quantify TLs, after
      each training session and match, players reported their session rating of
      perceived exertion (sRPE) separately for respiratory (sRPEres) and leg
      musculature (sRPEmus). Elite players accumulated greater weekly training volume
      (361 +/- 14 vs. 280 +/- 48 min; effect sizes (ES) = 5.23 +/- 1.74; most likely),
      and perceived respiratory (1460 +/- 184 vs. 1223 +/- 260 AU; ES = 1.12 +/- 0.79;
      very likely) and muscular (1548 +/- 216 vs. 1318 +/- 308 AU; ES = 0.99 +/- 0.84;
      likely) TL than did non-elite players. Training volume, sRPEres-TL and sRPEmus-TL
      were positively and largely correlated (r = 0.67-0.71) with the changes in
      aerobic fitness. The present results suggest that a low training volume and TL
      can impair improvement in aerobic fitness in junior soccer players during the in
      season period.

PMID- 26222604
TI  - Antimicrobial Photodynamic Therapy to treat chemotherapy-induced oral lesions:
      Report of three cases.
AB  - The development of Angular Cheilitis and the reactivation of Herpes Simplex
      Virus, could be related to a decrease in the resistance of the immune system in
      the infected host, being common in cancer patients receiving antineoplastic
      chemotherapy. The objective of the present manuscript is to report Antimicrobial
      Photodynamic Therapy as a treatment of infected oral lesions of patients
      submitted to chemotherapy. 

PMID- 26222605
TI  - New evidence for hybrid acrylic/TiO2 films inducing bacterial inactivation under
      low intensity simulated sunlight.
AB  - This study addresses the preparation and characterization of hybrid films
      prepared from Titanium dioxide (TiO2) Pickering stabilized acrylic polymeric
      dispersion as well as their bacterial inactivation efficiency under sunlight
      irradiation. Complete bacterial inactivation under low intensity simulated solar
      light irradiation (55 mW/cm(2)) was observed within 240 min for the films
      containing 10 weight based on monomers (wbm) % of TiO2, whereas 360 min were
      needed for the films containing 20 wbm% of TiO2. The hybrid films showed
      repetitive Escherichia coli (E. coli) inactivation under light irradiation. TiO2
      released from the films surfaces was measured by inductively coupled plasma mass
      spectrometry (IPC-MS), obtaining values of ~ 0.5 and 1 ppb/cm(2) for the films
      containing 10 wbm% and 20 wbm% of TiO2, respectively, far below the allowed
      cytotoxicity level for TiO2 (200 ppb). Transmission electron microscopy (TEM) of
      the hybrid films showed that TiO2 nanoparticles (NPs) were located at the polymer
      particle's surface forming a continuous inorganic network inside the film matrix.
      Atomic force microscopy (AFM) images showed differences in the TiO2 dispersion
      between the air-film and film-substrate interfaces. Films containing 10 wbm% of
      TiO2 had higher roughness (Rg) at both interfaces than the one containing 20 wbm%
      of TiO2 inducing an increase in the bacterial adhesion as well as the bacterial
      inactivation kinetics. The highly oxidative OH-radicals participating in the
      bacterial inactivation were determined by fluorescence.

PMID- 26222606
TI  - Limonoids with 11beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitory Activities
      from Dysoxylum mollissimum.
AB  - Thirteen new limonoids, dysoxylumosins A-M (1-13), along with six known analogues
      (14-19) were isolated from the twigs of Dysoxylum mollissimum. Their structures
      were established on the basis of spectroscopic data analysis. Compounds 1-6, 8,
      and 12 exhibited significant inhibitory activities against human and/or mouse
      11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Dysoxylumosin F (6),
      the most potent substance isolated, showed an IC50 value of 9.6 +/- 0.90 nM
      against human 11beta-HSD1.

PMID- 26222607
TI  - Vitamin D and cardiovascular risk among adults with obesity: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Obesity is a risk factor for both vitamin D deficiency and
      cardiovascular disease. A link between vitamin D status optimisation and improved
      cardiometabolic profile among adults with obesity could inform public health
      initiatives. METHODS: PubMed, Embase and Web of Science were searched for
      interventional studies examining the effects of vitamin D status improvement on
      cardiovascular risk factors (anthropometric measures, lipid profile, blood
      pressure, glucose tolerance) among nondiabetic adults with obesity. RESULTS:
      Seventeen publications reporting results from 11 different studies were included.
      Number of participants ranged from 34 to 1179 subjects. Duration was between 6
      weeks and 4 years. Vitamin D was administered as a supplement in ten studies
      (1000 IU daily to 120 000 IU fortnightly). In one study, participants were
      advised to increase sunlight exposure and dietary vitamin D intake. The random
      and fixed-effects meta-analysis showed that vitamin D significantly increased
      systolic blood pressure and LDL-C levels. The fixed-effects model also indicated
      a significant decrease in triglyceride levels, which was not evident using the
      random-effects model. Caution should be given to these results given the small
      number of studies used and the high heterogeneity between studies for the two
      latter outcomes. Additionally, a subset of eligible studies with compatible data
      presentation was included in the meta-analysis. CONCLUSION: This systematic
      review highlights a paucity of interventional studies examining the effects of
      vitamin D status improvement on cardiovascular risk factors among otherwise
      healthy adults with obesity. Large-scale studies at pharmacologically relevant
      doses and with sufficient duration are warranted.

PMID- 26222610
TI  - Simultaneous Block Bone Grafting Using "L-Shaped Notch" Preparation in Mandible:
      Case Series and 1-Year Follow-up.
AB  - PURPOSE: A novel autogenous block bone grafting technique with simultaneous
      placement of dental implants is described for several cases of horizontal ridge
      augmentation. METHODS: Seven patients with a mandibular horizontal ridge that was
      inadequate for proper implant placement were included in this study. Simultaneous
      implant placement and autogenous block bone grafting was planned; we designed the
      "L-shaped notch" preparation of the recipient site for the additional fixation
      with only 1 screw. This new technique also required minimal size of autogenous
      block bone. RESULTS: In total, 11 implants and final restorations were delivered
      in 7 patients. The dehiscence defects were covered successfully (79.70 +/- 5.58%;
      2.26 +/- 0.68 mm) at the uncover surgery. The marginal bone loss was 0.50 +/-
      0.26 mm on the mesial side and 0.58 +/- 0.23 mm on the distal side. The outcomes
      were satisfactory clinically and radiographically during the 1-year follow-up.
      CONCLUSION: Although additional studies, with more than 7 patients, are needed to
      evaluate the L-shaped notch preparation, this was effective to accomplish
      horizontal ridge augmentation simultaneously with the placement of dental
      implants using the minimal size of autogenous block bone.

PMID- 26222612
TI  - Measuring the bias, precision, accuracy, and validity of self-reported height and
      weight in assessing overweight and obesity status among adolescents using a
      surveillance system.
AB  - BACKGROUND: Evidence regarding bias, precision, and accuracy in adolescent self
      reported height and weight across demographic subpopulations is lacking. The
      bias, precision, and accuracy of adolescent self-reported height and weight
      across subpopulations were examined using a large, diverse and representative
      sample of adolescents. A second objective was to develop correction equations for
      self-reported height and weight to provide more accurate estimates of body mass
      index (BMI) and weight status. METHODS: A total of 24,221 students from 8th and
      11th grade in Texas participated in the School Physical Activity and Nutrition
      (SPAN) surveillance system in years 2000-2002 and 2004-2005. To assess bias, the
      differences between the self-reported and objective measures, for height and
      weight were estimated. To assess precision and accuracy, the Lin's concordance
      correlation coefficient was used. BMI was estimated for self-reported and
      objective measures. The prevalence of students' weight status was estimated using
      self-reported and objective measures; absolute (bias) and relative error
      (relative bias) were assessed subsequently. Correction equations for sex and
      race/ethnicity subpopulations were developed to estimate objective measures of
      height, weight and BMI from self-reported measures using weighted linear
      regression. Sensitivity, specificity and positive predictive values of weight
      status classification using self-reported measures and correction equations are
      assessed by sex and grade. RESULTS: Students in 8th- and 11th-grade overestimated
      their height from 0.68cm (White girls) to 2.02 cm (African-American boys), and
      underestimated their weight from 0.4 kg (Hispanic girls) to 0.98 kg (African
      American girls). The differences in self-reported versus objectively-measured
      height and weight resulted in underestimation of BMI ranging from -0.23 kg/m2
      (White boys) to -0.7 kg/m2 (African-American girls). The sensitivity of self
      reported measures to classify weight status as obese was 70.8% and 81.9% for 8th-
      and 11th-graders, respectively. These estimates increased when using the
      correction equations to 77.4% and 84.4% for 8th- and 11th-graders, respectively.
      CONCLUSIONS: When direct measurement is not practical, self-reported measurements
      provide a reliable proxy measure across grade, sex and race/ethnicity
      subpopulations of adolescents. Correction equations increase the sensitivity of
      self-report measures to identify prevalence of overall overweight/obesity status.

PMID- 26222613
TI  - Effects of individual, combined, and isolated physical activity behaviors on all
      cause mortality and CVD-specific mortality: Prospective cohort study among U.S.
      adults.
AB  - OBJECTIVE: To examine the individual, combined, and isolated effects of movement
      based behaviors (MBBs) on all-cause mortality and CVD-specific mortality.
      METHODS: The present prospective study included data from the 1999-2004 National
      Health & Nutrition Examination Survey, with follow-up data through December 31,
      2006 (N=12,321 U.S. adults). Measures included self-report engagement in 4 MBBs
      (moderate-intensity exercise, vigorous-intensity exercise, muscular strength
      activities, and active transport), with all-cause mortality and CVD-specific
      mortality as the outcome measures. RESULTS: Regarding all-cause mortality, the
      hazard ratio for those with 1 (vs. 0), 2 (vs. 0), and 3-4 (vs. 0) MBBs,
      respectively, was 0.61 (95% CI: 0.49-0.76), 0.49 (95% CI: 0.36-0.66), and 0.24
      (95% CI: 0.16-0.37). The only MBBs independently associated with all-cause
      mortality were vigorous exercise (HR=0.56; 95% CI: 0.41-0.76) and moderate
      intensity exercise (HR=0.58; 95% CI: 0.45-0.74). When examining the
      isolation/exclusivity effects of the MBBs, the only MBB performed in isolation
      that was statistically significantly associated with all-cause mortality was
      "Only VPA" (HR=0.45; 95% CI: 0.23-0.86). CVD-specific mortality results were
      similar to the all-cause mortality results. CONCLUSIONS: There was little
      evidence of a MBB isolation effect on mortality risk, but individuals engaging in
      more MBBs had a lower risk of all-cause mortality and CVD-specific mortality.
      These findings suggest that, in addition to promoting greater engagement in
      overall physical activity, recommendations for adults to engage in multiple MBBs
      may be advisable.

PMID- 26222614
TI  - Depressive-like symptoms in a reserpine-induced model of fibromyalgia in rats.
AB  - Since the pathogenesis of fibromyalgia is unknown, treatment options are limited,
      ineffective and in fact based on symptom relief. A recently proposed rat model of
      fibromyalgia is based on central depletion of monamines caused by reserpine
      administration. This model showed widespread musculoskeletal pain and depressive
      like symptoms, but the methodology used to measure such symptoms has been
      criticized. Evidence relates the high prevalence of pain and depression in
      fibromyalgia to common pathogenic pathways, most probably focused on the
      monoaminergic system. The present study aims at a validation of the reserpine
      model of fibromyalgia. For this purpose, rats undergoing this model have been
      tested for depressive-like symptoms with a Novelty-Suppressed Feeding Test
      adaptation. Animals administered with reserpine and subjected to forced food
      deprivation performed a smaller number of incursions to the center of the open
      field, evidenced by a decrease in the per-minute rate of the rats' approaching,
      smelling or touching the food. They also took more time to eat from the central
      food than control rats. These NSFT findings suggest the presence of depressive
      like disorders in this animal model of fibromyalgia. 

PMID- 26222616
TI  - Genomic Resources for Water Yam (Dioscorea alata L.): Analyses of EST-Sequences,
      De Novo Sequencing and GBS Libraries.
AB  - The reducing cost and rapid progress in next-generation sequencing techniques
      coupled with high performance computational approaches have resulted in large
      scale discovery of advanced genomic resources in several model and non-model
      plant species. Yam (Dioscorea spp.) is a major food and cash crop in many
      countries but research efforts have been limited to understand the genetics and
      generate genomic information for the crop. The availability of a large number of
      genomic resources including genome-wide molecular markers will accelerate the
      breeding efforts and application of genomic selection in yams. In the present
      study, several methods including expressed sequence tags (EST)-sequencing, de
      novo sequencing, and genotyping-by-sequencing (GBS) profiles on two yam
      (Dioscorea alata L.) genotypes (TDa 95/00328 and TDa 95-310) was performed to
      generate genomic resources for use in its improvement programs. This includes a
      comprehensive set of EST-SSRs, genomic SSRs, whole genome SNPs, and reduced
      representation SNPs. A total of 1,152 EST-SSRs were developed from >40,000 EST
      sequences generated from the two genotypes. A set of 388 EST-SSRs were validated
      as polymorphic showing a polymorphism rate of 34% when tested on two diverse
      parents targeted for anthracnose disease. In addition, approximately 40X de novo
      whole genome sequence coverage was generated for each of the two genotypes, and a
      total of 18,584 and 15,952 genomic SSRs were identified for TDa 95/00328 and TDa
      95-310, respectively. A custom made pipeline resulted in the selection of 573
      genomic SSRs common across the two genotypes, of which only eight failed, 478
      being polymorphic and 62 monomorphic indicating a polymorphic rate of 83.5%.
      Additionally, 288,505 high quality SNPs were also identified between these two
      genotypes. Genotyping by sequencing reads on these two genotypes also revealed
      36,790 overlapping SNP positions that are distributed throughout the genome. Our
      efforts in using different approaches in generating genomic resources provides a
      non-biased glimpse into the publicly available EST-sequences, yam genome, and GBS
      profiles with affirmation that the genomic complexity can be methodically
      unraveled and constitute a critical foundation for future studies in linkage
      mapping, germplasm analysis, and predictive breeding. 

PMID- 26222617
TI  - Correction: Rapid Response to Evaluate the Presence of Amphibian Chytrid Fungus
      (Batrachochytrium dendrobatidis) and Ranavirus in Wild Amphibian Populations in
      Madagascar.

PMID- 26222615
TI  - Representative Sinusoids for Hepatic Four-Scale Pharmacokinetics Simulations.
AB  - The mammalian liver plays a key role for metabolism and detoxification of
      xenobiotics in the body. The corresponding biochemical processes are typically
      subject to spatial variations at different length scales. Zonal enzyme expression
      along sinusoids leads to zonated metabolization already in the healthy state.
      Pathological states of the liver may involve liver cells affected in a zonated
      manner or heterogeneously across the whole organ. This spatial heterogeneity,
      however, cannot be described by most computational models which usually consider
      the liver as a homogeneous, well-stirred organ. The goal of this article is to
      present a methodology to extend whole-body pharmacokinetics models by a detailed
      liver model, combining different modeling approaches from the literature. This
      approach results in an integrated four-scale model, from single cells via
      sinusoids and the organ to the whole organism, capable of mechanistically
      representing metabolization inhomogeneity in livers at different spatial scales.
      Moreover, the model shows circulatory mixing effects due to a delayed
      recirculation through the surrounding organism. To show that this approach is
      generally applicable for different physiological processes, we show three
      applications as proofs of concept, covering a range of species, compounds, and
      diseased states: clearance of midazolam in steatotic human livers, clearance of
      caffeine in mouse livers regenerating from necrosis, and a parameter study on the
      impact of different cell entities on insulin uptake in mouse livers. The examples
      illustrate how variations only discernible at the local scale influence substance
      distribution in the plasma at the whole-body level. In particular, our results
      show that simultaneously considering variations at all relevant spatial scales
      may be necessary to understand their impact on observations at the organism
      scale. 

PMID- 26222618
TI  - Challenging the two concepts in determining the appropriate pre-discharge N
      terminal pro-brain natriuretic peptide treatment target in acute decompensated
      heart failure patients: absolute or relative discharge levels?
AB  - AIMS: NT-proBNP is a strong predictor for readmissions and mortality in acute
      decompensated heart failure (ADHF) patients. We assessed whether absolute or
      relative NT-proBNP levels should be used as pre discharge treatment target.
      METHODS AND RESULTS: Our study population was assembled from seven ADHF cohorts.
      We defined absolute (<1500, <3000, <5000, and <15 000 ng/L) and relative NT
      proBNP targets (>30, >50, and >70%). Population attributable risk fraction (PARF)
      is the proportion of all-cause 6-month mortality in the population that would be
      reduced if all patients attain the NT-proBNP target. PARF was determined for each
      target as well as the percentage of patients attaining the NT-proBNP target.
      Attainability was investigated by logistic regression analysis. A total of 1266
      patients [age 74 (64-80), 60% male] was studied. For every absolute NT-proBNP
      level, a corresponding percentage reduction was found that resulted in similar
      PARFs. The highest PARF (~60-70%) was observed for <1500 or >70%, but
      attainability was low (27% and 22%, respectively). The strongest predictor for
      not attaining these targets was admission NT-proBNP. In admission NT-proBNP
      tertiles, PARFs were significantly different for absolute, but not for relative
      targets. CONCLUSION: In an ADHF population, pre-discharge absolute or relative NT
      proBNP targets may both be useful as they have similar effects on PARF. However,
      depending on admission NT-proBNP, absolute targets show varying PARFs, while
      PARFs for relative targets were similar. A relative target is predicted to reduce
      mortality consistently across the whole spectrum of ADHF patients, while this is
      not the case using a single absolute target.

PMID- 26222620
TI  - Electrochemistry of La(0.3)Sr(0.7)Fe(0.7)Cr(0.3)O(3-delta) as an oxygen and fuel
      electrode for RSOFCs.
AB  - The use of a single porous mixed ion-electron conducting (MIEC) material as both
      the oxygen and fuel electrodes in reversible solid oxide cells is of increasing
      interest, primarily due to the resulting simplified cell design and lower
      manufacturing costs. In this work, La(0.3)Sr(0.7)Fe(0.7)Cr(0.3)O(3-delta) (LSFCr
      3) was studied in a 3-electrode half-cell configuration in air, pure CO2 and in a
      1 : 1 CO2 : CO mixture, over a temperature range of 650-800  degrees C. A
      detailed analysis of the impedance (EIS) data, under both open circuit and
      polarized conditions, as well as the cyclic voltammetry response of LSFCr-3 has
      shown that it is very active in all of these environments, but with oxygen
      evolution being somewhat more facile that oxygen reduction, and CO2 reduction
      more active than CO oxidation. Evidence for a chemical capacitance, associated
      with the Fe(3+/4+) redox process in LSFCr-3, was also obtained from the EIS and
      CV data in all gas environments.

PMID- 26222619
TI  - Pembrolizumab Cutaneous Adverse Events and Their Association With Disease
      Progression.
AB  - IMPORTANCE: Immunomodulatory anticancer drugs, such as the anti-programmed death
      1 drug pembrolizumab, have shown promising results in trials, and more patients
      will receive such treatments. Little is known about cutaneous adverse events
      (AEs) caused by these drugs and their possible correlation with treatment
      response. OBJECTIVE: To describe the frequency and spectrum of cutaneous AEs
      linked with pembrolizumab and their possible correlation with treatment response.
      DESIGN, SETTING, AND PARTICIPANTS: A single-institution, retrospective medical
      record review was conducted of patients with cancer who were treated with
      pembrolizumab from March 1, 2011, to May 28, 2014. The review comprised 83
      consecutive patients who were enrolled in 2 clinical trials, received at least 1
      dose of pembrolizumab, and had at least 1 follow-up visit. Patients were grouped
      according to the following therapeutic regimen for pembrolizumab: 43 received 10
      mg/kg every 3 weeks, 24 received 10 mg/kg every 2 weeks, and 16 received 2 mg/kg
      every 3 weeks. Sixty-six patients were treated for melanoma, 15 patients for lung
      cancer, 1 patient for prostate cancer, and 1 patient for Merkel cell carcinoma.
      Median follow-up was 15 weeks (range, 2-105 weeks). The analysis was conducted
      from March 1 to September 30, 2014. MAIN OUTCOMES AND MEASURES: Occurrence,
      severity, and type of cutaneous AEs, as well as disease progression and response
      to pembrolizumab treatment. RESULTS: Thirty-five patients (42%) developed
      cutaneous AEs attributed to pembrolizumab. The most common cutaneous AEs were
      macular papular eruption (24 [29%]), pruritus (10 [12%]), and hypopigmentation (7
      [8%]). All 7 patients who developed hypopigmentation were treated for melanoma.
      Survival analyses showed that patients who developed cutaneous AEs had
      significantly longer progression-free intervals in all 3 groups (pembrolizumab,
      10 mg/kg, every 3 weeks, P = .001; pembrolizumab, 10 mg/kg, every 2 weeks, P =
      .003; pembrolizumab, 2 mg/kg, every 3 weeks, P = .009) compared with patients who
      did not develop cutaneous AEs. CONCLUSIONS AND RELEVANCE: Pembrolizumab therapy
      was associated with cutaneous AEs in 42% of patients. The development of
      cutaneous AEs, especially of hypopigmentation in patients with melanoma, could
      point toward better treatment response.

PMID- 26222621
TI  - Microbial Population Differentials between Mucosal and Submucosal Intestinal
      Tissues in Advanced Crohn's Disease of the Ileum.
AB  - Since Crohn's disease is a transmural disease, we hypothesized that examination
      of deep submucosal tissues directly involved in the inflammatory disease process
      may provide unique insights into bacterial populations transgressing intestinal
      barriers and bacterial populations more representative of the causes and agents
      of the disease. We performed deep 16s microbiota sequencing on isolated ilea
      mucosal and submucosal tissues on 20 patients with Crohn's disease and 15 non
      inflammatory bowel disease controls with a depth of coverage averaging 81,500
      sequences in each of the 70 DNA samples yielding an overall resolution down to
      0.0001% of the bacterial population. Of the 4,802,328 total sequences generated,
      98.9% or 4,749,183 sequences aligned with the Kingdom Bacteria that clustered
      into 8545 unique sequences with <3% divergence or operational taxonomic units
      enabling the identification of 401 genera and 698 tentative bacterial species.
      There were significant differences in all taxonomic levels between the submucosal
      microbiota in Crohn's disease compared to controls, including organisms of the
      Order Desulfovibrionales that were present within the submucosal tissues of most
      Crohn's disease patients but absent in the control group. A variety of organisms
      of the Phylum Firmicutes were increased in the subjacent submucosa as compared to
      the parallel mucosal tissue including Ruminococcus spp., Oscillospira spp.,
      Pseudobutyrivibrio spp., and Tumebacillus spp. In addition, Propionibacterium
      spp. and Cloacibacterium spp. were increased as well as large increases in
      Proteobacteria including Parasutterella spp. and Methylobacterium spp. This is
      the first study to examine the microbial populations within submucosal tissues of
      patients with Crohn's disease and to compare microbial communities found deep
      within the submucosal tissues with those present on mucosal surfaces. Our data
      demonstrate the existence of a distinct submucosal microbiome and ecosystem that
      is not well reflected in the mucosa and/or downstream fecal material. 

PMID- 26222622
TI  - Biomimetic superhydrophobic surfaces by combining mussel-inspired adhesion with
      lotus-inspired coating.
AB  - Superhydrophobic surfaces on PET textiles were fabricated by combined
      bioinspiration from the strong adhesion of marine mussels and the two-scale
      structure of lotus leaves under mild conditions. Dopamine can spontaneously
      polymerize in alkaline aqueous solution to form a thin adhesive layer of
      polydopamine (PDA) wrapping on the micro-scale fibers. The as-formed thin PDA
      layer worked as a reactive template to generate PDA nanoparticles decorated on
      the fiber surfaces, imparting the textiles with excellent UV-shielding properties
      as well as a hierarchical structure similar to the morphology of the lotus leaf.
      After further modification with perfluorodecyl trichlorosilane, the textiles
      turned superhydrophobic with a water contact angle higher than 150 degrees . Due
      to the strong adhesion of PDA to a wide range of materials, the present strategy
      may be extendable to fabrication of superhydrophobic surfaces on a variety of
      other substrates. 

PMID- 26222623
TI  - Desmopressin Use in the Treatment of Aripiprazole-Induced Nocturnal Enuresis in a
      Child Diagnosed with Autistic Disorder.

PMID- 26222624
TI  - Measuring Food Brand Awareness in Australian Children: Development and Validation
      of a New Instrument.
AB  - BACKGROUND: Children's exposure to food marketing is one environmental
      determinant of childhood obesity. Measuring the extent to which children are
      aware of food brands may be one way to estimate relative prior exposures to food
      marketing. This study aimed to develop and validate an Australian Brand Awareness
      Instrument (ABAI) to estimate children's food brand awareness. METHODS: The ABAI
      incorporated 30 flashcards depicting food/drink logos and their corresponding
      products. An abbreviated version was also created using 12 flashcards (ABAI-a).
      The ABAI was presented to 60 primary school aged children (7-11 yrs) attending
      two Australian after-school centres. A week later, the full-version was repeated
      on approximately half the sample (n=27) and the abbreviated-version was presented
      to the remaining half (n=30). The test-retest reliability of the ABAI was
      analysed using Intra-class correlation coefficients. The concordance of the ABAI
      a and full-version was assessed using Bland-Altman plots. The 'nomological'
      validity of the full tool was investigated by comparing children's brand
      awareness with food marketing-related variables (e.g. television habits, intake
      of heavily promoted foods). RESULTS: Brand awareness increased with age (p<0.01)
      but was not significantly correlated with other variables. Bland-Altman analyses
      showed good agreement between the ABAI and ABAI-a. Reliability analyses revealed
      excellent agreement between the two administrations of the full-ABAI.
      CONCLUSIONS: The ABAI was able to differentiate children's varying levels of
      brand awareness. It was shown to be a valid and reliable tool and may allow
      quantification of brand awareness as a proxy measure for children's prior food
      marketing exposure.

PMID- 26222625
TI  - The biomolecular corona of nanoparticles in circulating biological media.
AB  - When nanoparticles come into contact with biological media, they are covered by a
      biomolecular 'corona', which confers a new identity to the particles. In all the
      studies reported so far nanoparticles are incubated with isolated plasma or serum
      that are used as a model for protein adsorption. Anyway, bodily fluids are
      dynamic in nature so the question arises on whether the incubation protocol, i.e.
      dynamic vs. static incubation, could affect the composition and structure of the
      biomolecular corona. Here we let multicomponent liposomes interact with fetal
      bovine serum (FBS) both statically and dynamically, i.e. in contact with
      circulating FBS (~40 cm s(-1)). The structure and composition of the liposome
      protein corona, as determined by dynamic light scattering, electrophoretic light
      scattering and liquid chromatography tandem mass spectrometry, were found to be
      dependent on the incubation protocol. Specifically, following dynamic exposure to
      FBS, multicomponent liposomes were less enriched in complement proteins and
      appreciably more enriched in apolipoproteins and acute phase proteins (e.g. alpha
      1-antitrypsin and inter-alpha-trypsin inhibitor heavy chain H3) that are involved
      in relevant interactions between nanoparticles and living systems. Supported by
      our results, we speculate that efficient predictive modeling of nanoparticle
      behavior in vivo will require accurate knowledge of nanoparticle-specific protein
      fingerprints in circulating biological media. 

PMID- 26222626
TI  - Multiresolution Topological Simplification.
AB  - Persistent homology has been advocated as a new strategy for the topological
      simplification of complex data. However, it is computationally intractable for
      large data sets. In this work, we introduce multiresolution persistent homology
      for tackling large datasets. Our basic idea is to match the resolution with the
      scale of interest so as to create a topological microscopy for the underlying
      data. We adjust the resolution via a rigidity density-based filtration. The
      proposed multiresolution topological analysis is validated by the study of a
      complex RNA molecule. 

PMID- 26222643
TI  - Management of toxicities following pelvic irradiation for gynaecological cancers.
AB  - PURPOSE OF REVIEW: With increasing numbers of cancer survivors, management of the
      consequences of treatment is a major clinical problem. This article discusses
      recent advances in preventing and managing radiotherapy-related toxicity. RECENT
      FINDINGS: Often underreported in clinical studies, radiation toxicity should be
      assessed with validated assessment tools to assess impact on quality of life.
      Prevention strategies targeting reactive oxygen species and proinflammatory
      cytokines show promise. Bowel toxicity is the most common late effect, and
      algorithm-led investigation and management can significantly improve outcomes.
      Oral and intravesical therapies are options for bladder toxicity if conservative
      measures fail. SUMMARY: With better understanding of the mechanisms of acute and
      chronic radiation-induced changes, more effective treatments are now possible.
      Following pelvic radiotherapy, patients should be proactively assessed for early
      intervention by a specialist multidisciplinary team.

PMID- 26222644
TI  - Alpha-2 agonists: back to the future of human anesthesia?

PMID- 26222645
TI  - Visualization of Lipid Membrane Reorganization Induced by a Pore-Forming Toxin
      Using High-Speed Atomic Force Microscopy.
AB  - We examined the effect of a sphingomyelin (SM)-binding pore-forming toxin (PFT),
      lysenin, on the dynamics of a phase-separated membrane of SM, where SM formed
      liquid-ordered (Lo) domains with cholesterol (Chol) within a phosphatidylcholine
      rich liquid-disordered (Ld) phase. We visualized the lysenin-induced membrane
      reorganization using high-speed atomic force microscope (HS-AFM). Lysenin
      oligomerized on the SM-rich Lo domain and simultaneously its oligomers assembled
      into a hexagonal close-packed (hcp) structure. The phase boundary was stable
      during the assembling of lysenin on the SM-rich domain, indicating that lysenin
      did not affect the line tension between Lo and Ld phases. After the full coverage
      of the SM-rich domain by oligomers, their hcp assembly gradually expanded into
      the Ld phase and eventually covered the entire membrane. Our results suggest that
      pore formation, i.e., insertion of lysenin into the membrane in its oligomeric
      state, induced the exclusion of SM and Chol from the SM-rich domain, which was
      followed by further binding and oligomerization of lysenin. 

PMID- 26222647
TI  - Engineering of a Secretory Active Three-Dimensional Lacrimal Gland Construct on
      the Basis of Decellularized Lacrimal Gland Tissue.
AB  - Lacrimal gland (LG) insufficiency is a main cause for severe dry eye leading to
      pain, visual impairment, and eventually loss of sight. Engineering of
      transplantable LG tissue with secretory capacity is a desirable goal. In this
      study, a three-dimensional decellularized LG (DC-LG) scaffold with preserved LG
      morphology was generated by treatment with 1% sodium deoxycholate and DNase
      solution using porcine LG tissue. To address clinical applicability, the primary
      in vitro culture of secretory active LG cells from a small tissue biopsy of 1.5
      mm diameter was introduced and compared with an established isolation method by
      enzymatic digestion. Cells from both isolation methods depicted an epithelial
      phenotype, maintained their secretory capacity for up to 30 days, and exhibited
      progenitor cell capacity as measured by aldehyde dehydrogenase-1 activity, side
      population assay, and colony-forming units. Cells from passage 0 were reseeded
      into the DC-LG and secretory active cells migrated into the tissue. The cells
      resembled an LG-like morphology and the constructs showed secretory activity.
      These results demonstrate the possibility of engineering a secretory competent,
      three-dimensional LG construct using LG cells expanded from a small tissue biopsy
      and DC-LG as a matrix that provides the native structure and physiological niche
      for these cells. 

PMID- 26222648
TI  - Effects of a physical fitness program on memory and blood viscosity in sedentary
      elderly men.
AB  - The aim of this study was to investigate the effects of a 6-month exercise
      program on cognitive function and blood viscosity in sedentary elderly men. Forty
      six healthy inactive men, aged 60-75 years were randomly distributed into a
      control group (n=23) and an experimental group (n=23). Participants underwent
      blood analysis and physical and memory evaluation, before and after the 6-month
      program of physical exercise. The control group was instructed not to alter its
      everyday activities; the experimental group took part in the fitness program. The
      program was conducted using a cycle ergometer, 3 times per week on alternate
      days, with intensity and volume individualized at ventilatory threshold 1.
      Sessions were continuous and maximum duration was 60 min each. There was
      significant improvement in memory (21%; P<0.05), decreased blood viscosity (-19%;
      P<0.05), and higher aerobic capacity (48%; P<0.05) among participants in the
      experimental group compared with the control group. These data suggest that
      taking part in an aerobic physical fitness program at an intensity corresponding
      to ventilatory threshold-1 may be considered a nonmedication alternative to
      improve physical and cognitive function. 

PMID- 26222650
TI  - Physical exercise prevents motor disorders and striatal oxidative imbalance after
      cerebral ischemia-reperfusion.
AB  - Stroke is the third most common cause of death worldwide, and most stroke
      survivors present some functional impairment. We assessed the striatal oxidative
      balance and motor alterations resulting from stroke in a rat model to investigate
      the neuroprotective role of physical exercise. Forty male Wistar rats were
      assigned to 4 groups: a) control, b) ischemia, c) physical exercise, and d)
      physical exercise and ischemia. Physical exercise was conducted using a treadmill
      for 8 weeks. Ischemia-reperfusion surgery involved transient bilateral occlusion
      of the common carotid arteries for 30 min. Neuromotor performance (open-field and
      rotarod performance tests) and pain sensitivity were evaluated beginning at 24 h
      after the surgery. Rats were euthanized and the corpora striata was removed for
      assay of reactive oxygen species, lipoperoxidation activity, and antioxidant
      markers. Ischemia-reperfusion caused changes in motor activity. The ischemia
      induced alterations observed in the open-field test were fully reversed, and
      those observed in the rotarod test were partially reversed, by physical exercise.
      Pain sensitivity was similar among all groups. Levels of reactive oxygen species
      and lipoperoxidation increased after ischemia; physical exercise decreased
      reactive oxygen species levels. None of the treatments altered the levels of
      antioxidant markers. In summary, ischemia-reperfusion resulted in motor
      impairment and altered striatal oxidative balance in this animal model, but those
      changes were moderated by physical exercise. 

PMID- 26222652
TI  - Elevated serum creatinine and low albumin are associated with poor outcomes in
      patients with liposarcoma.
AB  - Low serum albumin levels and impaired kidney function have been associated with
      decreased survival in patients with a variety of cancer types. In a retrospective
      cohort study, we analyzed 84 patients with liposarcoma treated at from May 1994
      to October 2011. Uni- and multivariable Cox proportional hazard models and
      competing risk analyses were performed to evaluate the association between
      putative biomarkers with disease-specific and overall survival. The median age of
      the study population was 51.7 (range 19.6-83.8) years. In multivariable analysis
      adjusted for AJCC tumor stage, serum creatinine was highly associated with
      disease-specific survival (Subdistribution Hazard ratio (SHR) per 1 mg/dl
      increase = 2.94; 95%CI 1.39-6.23; p = 0.005). High albumin was associated with
      improved overall and disease-specific survival (Hazard Ratio (HR) per 10 units
      increase = 0.50; 95%CI 0.26-0.95; p = 0.033 and SHR = 0.64; 95%CI 0.42-1.00; p =
      0.049). The serum albumin-creatinine-ratio emerged to be associated with both
      overall and disease-specific survival after adjusting for AJCC tumor stage (HR =
      0.95; 95%CI 0.92-0.99; p = 0.011 and SHR = 0.96; 95%CI 0.93-0.99; p = 0.08). Our
      study provides evidence for a tumor-stage-independent association between higher
      creatinine and lower albumin with worse disease-specific survival. Low albumin
      and a high albumin-creatinine-ratio independently predict poor overall survival.
      Our work identified novel prognostic biomarkers for prognosis of patients with
      liposarcoma.

PMID- 26222653
TI  - Synthesis and Biological Activity Evaluation of Novel alpha-Amino Phosphonate
      Derivatives Containing a Pyrimidinyl Moiety as Potential Herbicidal Agents.
AB  - To find novel high-activity and low-toxicity herbicide lead compounds with novel
      herbicidal mode of action, series of novel alpha-amino phosphonate derivatives
      containing a pyrimidinyl moiety, I, II, III, and IV, were designed and
      synthesized by Lewis acid (magnesium perchlorate) catalyzed Mannich-type reaction
      of aldehydes, amines, and phosphites. Their structures were clearly identified by
      spectroscopy data (IR, (1)H NMR, (31)P NMR, EI-MS) and elemental analyses. The
      bioassay [in vitro, in vivo (GH1 and GH2)] showed that most compounds I exhibited
      good herbicidal activities; for example, the activities of compounds Ib, Ic, Ig,
      Ii, Ik, and Im were as good as the positive control herbicides (acetochlor,
      atrazine, mesotrione, and glyphosate). However, their structural isomers II and
      III and analogues IV did not display any herbicidal activities in vivo, although
      some of them possessed selective inhibitory activity against Arabidopsis thaliana
      in vitro. Interestingly, it was found that compounds IVs, IVt, and IVl showed
      selective insecticidal activities against Aphis species or Plutella xylostella,
      respectively. Their preliminary herbicidal mode of action and structure-activity
      relationships were also studied. 

PMID- 26222651
TI  - MsmK, an ATPase, Contributes to Utilization of Multiple Carbohydrates and Host
      Colonization of Streptococcus suis.
AB  - Acquisition and metabolism of carbohydrates are essential for host colonization
      and pathogenesis of bacterial pathogens. Different bacteria can uptake different
      lines of carbohydrates via ABC transporters, in which ATPase subunits energize
      the transport though ATP hydrolysis. Some ABC transporters possess their own
      ATPases, while some share a common ATPase. Here we identified MsmK, an ATPase
      from Streptococcus suis, an emerging zoonotic bacterium causing dead infections
      in pigs and humans. Genetic and biochemistry studies revealed that the MsmK was
      responsible for the utilization of raffinose, melibiose, maltotetraose, glycogen
      and maltotriose. In infected mice, the msmK-deletion mutant showed significant
      defects of survival and colonization when compared with its parental and
      complementary strains. Taken together, MsmK is an ATPase that contributes to
      multiple carbohydrates utilization and host colonization of S. suis. This study
      gives new insight into our understanding of the carbohydrates utilization and its
      relationship to the pathogenesis of this zoonotic pathogen. 

PMID- 26222654
TI  - Prevalence of noncaesarean uterine surgical scars in a maternity population.
AB  - The prevalence of noncaesarean section uterine surgical scars in a general
      obstetric population was 3.0 of 1000 deliveries and among nulliparae 3.4 of 1000
      deliveries, calculated from population data of all delivery records in New South
      Wales from 2005 to 2011. As the population prevalence is low, women with a
      noncaesarean section uterine surgical scar are unlikely to impact the analyses of
      factors associated with caesarean section. 

PMID- 26222655
TI  - Patient and Referring Practitioner Characteristics Associated With the Likelihood
      of Undergoing Bariatric Surgery: A Systematic Review.
AB  - IMPORTANCE: Although bariatric surgery is the most cost-effective treatment for
      severe obesity, less than 1% of severely obese patients undergo it. Reasons for
      this low use are unclear. OBJECTIVES: To identify patient and referring
      practitioner characteristics associated with the likelihood of undergoing
      bariatric surgery. EVIDENCE REVIEW: The PubMed, PsycINFO, CINAHL, and Cochrane
      databases were searched for articles published from January 1, 1998, through
      December 31, 2014. Studies were eligible if they presented descriptive data
      regarding facilitators or barriers to bariatric surgery or if they reported
      statistical associations between patient or practitioner characteristics and
      referral to or receipt of bariatric surgery. Frequency effect sizes were
      calculated as the proportion of studies reporting a finding. FINDINGS: Of the
      7212 records identified in the initial search, 53 were included in full-text
      review. Nine studies met our inclusion criteria and were included in analyses. Of
      those, 4 included descriptive findings, 6 reported statistical associations, and
      1 included both. One study included practitioners as participants, whereas 8
      included patients. Four of 9 studies identified an association between female sex
      and a greater willingness to undergo bariatric surgery. Lack of knowledge about
      bariatric surgery was a barrier in 2 studies. Five of 9 cited patient concerns
      about the outcomes and safety of bariatric surgery as a barrier to undergoing it.
      Patients were more likely to pursue bariatric surgery when it was recommended by
      referring practitioners. Practitioners who believed that obesity treatment should
      be covered by insurance were more likely to recommend bariatric surgery.
      CONCLUSIONS AND RELEVANCE: Limited patient and referring practitioner knowledge
      about the safety and effectiveness of bariatric surgery are important barriers to
      bariatric surgery use. Future efforts focused on improving knowledge and
      identification of the critical determinants of obesity treatment decision making
      from the practitioner and patient perspectives would have an important effect on
      public health.

PMID- 26222656
TI  - PbI2-Based Dipping-Controlled Material Conversion for Compact Layer Free
      Perovskite Solar Cells.
AB  - A two-step sequential deposition method has been extensively employed to prepare
      the CH3NH3PbI3 active layer from the PbI2 precursor in perovskite solar cells
      (PSCs). The variation of the photovoltaic performance of PSCs made by this method
      was always attributed to different dipping times that induce complete/incomplete
      conversion of PbI2 into CH3NH3PbI3. To solve this issue, we employed a solvent
      vapor annealing (SVA) method to prepare PbI2 crystallites with large grain size
      for preparation of high quality perovskite. With this method, the increased PbI2
      dipping time in CH3NH3I solution was found to reduce the photovoltaic performance
      of resulting PSCs without a significant change in PbI2/CH3NH3PbI3 contents in the
      perovskite films. We attribute this abnormal reduction of the photovoltaic
      performance to intercalation/deintercalation of the PbI2 core with a CH3NH3PbI3
      shell, which causes the doping effect on both the PbI2 and CH3NH3PbI3 crystal
      lattices and the formation of a CH3NH3PbI3 capping layer on the surface, as
      revealed by UV-vis absorption, X-ray diffraction, FT-IR, and scanning electron
      microscope measurements. Based on our findings, a multistep dipping-drying
      process was employed as an alternative method to improve the crystalline quality.
      The method achieved power conversion efficiency up to 11.4% for the compact layer
      free PSC sharing a simple device structure of ITO/perovskite/spiro-OMeTAD/Ag. 

PMID- 26222658
TI  - Adrenal Suppression in EoE Treated With Budesonide?

PMID- 26222659
TI  - FTO Polymorphism rs9939609 Contributes to Weight Changes in Children With Celiac
      Disease on Gluten-Free Diet.
AB  - OBJECTIVES: Studies of adults and children with celiac disease have reported an
      increased risk of overweight during gluten-free diet (GFD). The fat mass and
      obesity-associated gene (FTO) variant rs9939609 has been associated with
      increased risk of developing obesity in children and adults. METHODS: In our
      study, we analyzed the effect of this variant on weight gain in a cohort of 280
      children with celiac disease on GFD. RESULTS: We found that after a mean follow
      up time of 3.0 years on GFD, FTO polymorphism influenced significantly the mean
      change in body mass index z score (P = 0.01). CONCLUSIONS: We conclude that the
      FTO gene contributes to determine weight changes in children with celiac disease
      on GFD.

PMID- 26222657
TI  - Sequence- and Structure-Based Immunoreactive Epitope Discovery for Burkholderia
      pseudomallei Flagellin.
AB  - Burkholderia pseudomallei is a Gram-negative bacterium responsible for
      melioidosis, a serious and often fatal infectious disease that is poorly
      controlled by existing treatments. Due to its inherent resistance to the major
      antibiotic classes and its facultative intracellular pathogenicity, an effective
      vaccine would be extremely desirable, along with appropriate prevention and
      therapeutic management. One of the main subunit vaccine candidates is flagellin
      of Burkholderia pseudomallei (FliCBp). Here, we present the high resolution
      crystal structure of FliCBp and report the synthesis and characterization of
      three peptides predicted to be both B and T cell FliCBp epitopes, by both
      structure-based in silico methods, and sequence-based epitope prediction tools.
      All three epitopes were shown to be immunoreactive against human IgG antibodies
      and to elicit cytokine production from human peripheral blood mononuclear cells.
      Furthermore, two of the peptides (F51-69 and F270-288) were found to be dominant
      immunoreactive epitopes, and their antibodies enhanced the bactericidal
      activities of purified human neutrophils. The epitopes derived from this study
      may represent potential melioidosis vaccine components. 

PMID- 26222660
TI  - Prevalence and Clinical Significance of Herpesvirus Infection in Populations of
      Australian Marsupials.
AB  - Herpesviruses have been reported in several marsupial species, but molecular
      classification has been limited to four herpesviruses in macropodids, a
      gammaherpesvirus in two antechinus species (Antechinus flavipes and Antechinus
      agilis), a gammaherpesvirus in a potoroid, the eastern bettong (Bettongia
      gaimardi) and two gammaherpesviruses in koalas (Phascolarctos cinereus). In this
      study we examined a range of Australian marsupials for the presence of
      herpesviruses using molecular and serological techniques, and also assessed risk
      factors associated with herpesvirus infection. Our study population included 99
      koalas (Phascolarctos cinereus), 96 eastern grey kangaroos (Macropus giganteus),
      50 Tasmanian devils (Sarcophilus harrisii) and 33 common wombats (Vombatus
      ursinius). In total, six novel herpesviruses (one alphaherpesvirus and five
      gammaherpesviruses) were identified in various host species. The overall
      prevalence of detection of herpesvirus DNA in our study population was 27.2% (95%
      confidence interval (CI) of 22.6-32.2%), but this varied between species and
      reached as high as 45.4% (95% CI 28.1-63.7%) in common wombats. Serum antibodies
      to two closely related macropodid herpesviruses (macropodid herpesvirus 1 and 2)
      were detected in 44.3% (95% CI 33.1-55.9%) of animals tested. This also varied
      between species and was as high as 92% (95% CI 74.0-99.0%) in eastern grey
      kangaroos. A number of epidemiological variables were identified as positive
      predictors for the presence of herpesvirus DNA in the marsupial samples
      evaluated. The most striking association was observed in koalas, where the
      presence of Chlamydia pecorum DNA was strongly associated with the presence of
      herpesvirus DNA (Odds Ratio = 60, 95% CI 12.1-297.8). Our results demonstrate the
      common presence of herpesviruses in Australian marsupials and provide directions
      for future research.

PMID- 26222661
TI  - ISSLS Prize Winner: Dynamic Loading-Induced Convective Transport Enhances
      Intervertebral Disc Nutrition.
AB  - STUDY DESIGN: Experimental animal study of convective transport in the
      intervertebral disc. OBJECTIVE: To quantify the effects of mechanical loading
      rate on net transport into the healthy and degenerative intervertebral disc in
      vivo. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration is linked with
      a reduction in transport to the avascular disc. Enhancing disc nutrition is,
      therefore, a potential strategy to slow or reverse the degenerative cascade.
      Convection induced by mechanical loading is a potential mechanism to augment
      diffusion of small molecules into the disc. METHODS: Skeletally mature New
      Zealand white rabbits with healthy discs and discs degenerated via needle
      puncture were subjected to low rate axial compression and distraction loading for
      2.5, 5, 10, 15, or 20 minutes after a bolus administration of gadodiamide.
      Additional animals with healthy discs were subjected to high-rate loading for 10
      minutes or no loading for 10 minutes. Transport into the disc for each loading
      regimen was quantified using post-contrast-enhanced magnetic resonance imaging.
      RESULTS: Low-rate loading resulted in the rapid uptake and clearance of
      gadodiamide in the disc. Low-rate loading increased net transport into the
      nucleus by a mean 16.8% and 12.6% in healthy and degenerative discs,
      respectively. The kinetics of small molecule uptake and clearance were
      accelerated in both healthy and degenerative discs with low-rate loading. In
      contrast, high-rate loading reduced transport into nucleus by a mean 16.8%.
      CONCLUSION: These results illustrate that trans-endplate diffusion can be
      enhanced by forced convection in both healthy and degenerative discs in vivo.
      Mechanical loading-induced convection could offer therapeutic benefit for
      degenerated discs by enhancing uptake of nutrients and clearance of by-products.
      LEVEL OF EVIDENCE: 4.

PMID- 26222662
TI  - How Does the Supine MRI Correlate With Standing Radiographs of Different Curve
      Severity in Adolescent Idiopathic Scoliosis?
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To study how the supine magnetic
      resonance image (MRI) correlates with standing radiographs of different curve
      severity in adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA:
      Linear correlation between Cobb angles measured on supine MRI and standing
      radiographs has been identified. However, the effects of different curve severity
      on the correlation have not been studied in depth. METHODS: Girls with AIS with
      standing radiographs and supine MRI were reviewed. From standing radiographs, all
      structural and nonstructural Cobb angles were measured. For those with
      simultaneous lateral radiographs, thoracic kyphosis (TK) and lumbar lordosis (LL)
      angles were measured. On supine MRI, the coronal Cobb angles, TK and LL were
      measured accordingly. The coronal Cobb angles were divided into 3 groups based on
      values measured on standing radiographs: mild group for Cobb angles less than 20
      degrees , moderate group for 20 degrees  to 40 degrees , and severe group for
      more than 40 degrees . Correlation was analyzed using scatter plot. RESULTS:
      Eighty patients with AIS with 122 coronal curves were reviewed. On standing
      radiographs, the coronal Cobb angles were 14.7 degrees +/- 3.2 degrees , 28.2
      degrees +/- 5.1 degrees , and 54.9 degrees +/- 11.3 degrees  for mild, moderate,
      and severe groups. On supine MRI, the Cobb angles averaged 10.1 degrees +/- 5.6
      degrees , 20.0 degrees +/- 6.3 degrees , and 49.4 +/- 12.3 degrees  for each
      group, respectively. TK were 16.3 +/- 9.1 degrees  and 11.8 +/- 6.1 degrees  for
      radiographs and MRI (P < 0.001), whereas the LL averaged 45.5 +/- 12.2 degrees 
      and 39.5 +/- 10.5 degrees  for radiographs and MRI (P < 0.001). Cobb angles
      measured on standing radiographs and supine MRI were linearly correlated with the
      adjusted R being 0.0627, 0.2118, and 0.7999 for the mild, moderate, and severe
      groups. CONCLUSION: Cobb angles measured on supine MRI were linearly correlated
      with Cobb angles measured on standing radiographs and the correlation was more
      reliable in those with Cobb angles more than 40 degrees . Therefore, the supine
      MRI could serve as a reliable alternative to standing radiographs in the
      assessment of Cobb angles more than 40 degrees  in AIS. LEVEL OF EVIDENCE: 3.

PMID- 26222663
TI  - Evaluation of the Fixation Strength of Pedicle Screws Using Cortical Bone
      Trajectory: What Is the Ideal Trajectory for Optimal Fixation?
AB  - STUDY DESIGN: In vivo analysis of insertional torque of pedicle screws using
      cortical bone trajectory (CBT) technique. OBJECTIVE: To investigate factors
      contributing to the fixation strength of CBT screws and to clarify the ideal
      cortical trajectory for lumbar fusion. SUMMARY OF BACKGROUND DATA: CBT has
      developed as a new minimally invasive technique of lumbar instrumentation.
      Despite biomechanical studies demonstrating the superior characteristics of CBT,
      no study has elucidated the most suitable path for optimal fixation or compared
      the fixation within variations of trajectory. METHODS: The insertional torque of
      pedicle screws using CBT was measured intraoperatively in 72 consecutive
      patients. The detailed positions of a total of 268 screws were confirmed using
      postoperative reconstruction computed tomographic scans and were analyzed to
      identify factors contributing to the level of insertional torque. Investigated
      factors were as follows: (1) age, (2) bone mineral density of the femoral neck
      and lumbar vertebrae by dual-energy x-ray absorptiometry; (3) the pedicle width
      and height, (4) the length of the implant, (5) total screw length within the
      vertebra, (6) the screw length within the vertebral body, (7) the screw length
      within the lamina, (8) the cephalad and lateral angle of the trajectory, and (9)
      the distance from the long axis of the screw to the inferior and medial borders
      of the pedicle. RESULTS: Multiple regression analysis showed that bone mineral
      density of the femoral neck, screw length within the lamina, and cephalad angle
      were significant independent factors affecting torque. CONCLUSION: The fixation
      of CBT screws varied depending on technical factors (cephalad angle and screw
      length within the lamina) as well as the individual patient factor of bone
      mineral density. The ideal trajectory was directed 25 degrees  to 30 degrees 
      cranially along the inferior border of the pedicle so as to obtain maximum
      contact with the lamina and sufficient length within the vertebral body. LEVEL OF
      EVIDENCE: 2.

PMID- 26222664
TI  - The Deformity Angular Ratio: Does It Correlate With High-Risk Cases for Potential
      Spinal Cord Monitoring Alerts in Pediatric 3-Column Thoracic Spinal Deformity
      Corrective Surgery?
AB  - STUDY DESIGN: A retrospective analysis. OBJECTIVE: The purpose of this study was
      to determine whether the deformity angular ratio (DAR) can reliably assess the
      neurological risks of patients undergoing deformity correction. SUMMARY OF
      BACKGROUND DATA: Identifying high-risk patients and procedures can help ensure
      that appropriate measures are taken to minimize neurological complications during
      spinal deformity corrections. Subjectively, surgeons look at radiographs and
      evaluate the riskiness of the procedure. However, 2 curves of similar magnitude
      and location can have significantly different risks of neurological deficit
      during surgery. Whether the curve spans many levels or just a few can
      significantly influence surgical strategies. Lenke et al have proposed the DAR,
      which is a measure of curve magnitude per level of deformity. METHODS: The data
      from 35 pediatric spinal deformity correction procedures with thoracic 3-column
      osteotomies were reviewed. Measurements from preoperative radiographs were used
      to calculate the DAR. Binary logistic regression was used to model the
      relationship between DARs (independent variables) and presence or absence of an
      intraoperative alert (dependent variable). RESULTS: In patients undergoing 3
      column osteotomies, sagittal curve magnitude and total curve magnitude were
      associated with increased incidence of transcranial motor evoked potential
      changes. Total DAR greater than 45 degrees  per level and sagittal DAR greater
      than 22 degrees  per level were associated with a 75% incidence of a motor evoked
      potential alert, with the incidence increasing to 90% with sagittal DAR of 28
      degrees  per level. CONCLUSION: In patients undergoing 3-column osteotomies for
      severe spinal deformities, the DAR was predictive of patients developing
      intraoperative motor evoked potential alerts. Identifying accurate
      radiographical, patient, and procedural risk factors in the correction of severe
      deformities can help prepare the surgical team to improve safety and outcomes
      when carrying out complex spinal corrections. LEVEL OF EVIDENCE: 3.

PMID- 26222665
TI  - Letter. IN RESPONSE: Re: Gabel et al. Commenting on Linton et al. Development of
      a Short Form of the Orebro Musculoskeletal Pain Screening Questionnaire.

PMID- 26222668
TI  - Resilience in lesbians and gay men: A review and key findings from a nationwide
      Australian survey.
AB  - Rates of depression and anxiety are disproportionately high among lesbians and
      gay men, and stigma-related stress is thought to be a major factor. While
      reducing stigma remains a priority, developing ways to assist lesbians and gay
      men to build resilience to stigma-related stress is also a growing priority among
      policymakers and health professionals. This article summarizes major conceptual
      work and research on resilience among lesbians and gay men, including key
      findings from a nationwide online survey involving 2,793 Australian lesbians and
      gay men aged 16 years and older that examined demographic and psychosocial
      factors related to resilience. Research on resilience in gay and lesbian
      populations is currently a small field but appears to be growing. As recommended
      in this article, further work is needed to identify circumstances in which
      lesbians and gay men display resilience to stigma-related stress and to
      systematically test resilience training programmes that help to prevent
      depression and anxiety in these at-risk populations. 

PMID- 26222667
TI  - p53-p66(shc)/miR-21-Sod2 signaling is critical for the inhibitory effect of
      betulinic acid on hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third
      cause of cancer-related death. Betulinic acid (BA) is a pentacyclic triterpene,
      possessing potential pro-apoptotic activities. The present study was designed to
      evaluate the effect of BA on tumor growth in mice and HCC cell proliferation in
      vitro. We found that BA dose-dependently inhibited tumor growth in mice induced
      by DEN plus CCl4 (D/C) and suppressed cell viability and proliferation in several
      HCC cell lines. In addition, BA increased mitochondrial ROS generation and
      mitochondrial dysfunction, activating molecular apoptotic events and leading to
      apoptotic cell death. p53 was increased by BA in D/C-treated mice and HCC cells
      and inhibition of p53 significantly suppressed the pro-apoptotic and anti-tumor
      effect of BA. Increase of p66(shc) was involved in the pro-apoptotic and anti
      tumor effect of BA. Moreover, BA-induced increase of p66(shc) was dependent upon
      p53. Sod2 expression was reduced by BA treatment, and a Sod2 mimic (MnTBAP)
      significantly blocked the pro-apoptotic and anti-tumor effect of BA. Furthermore,
      miR-21 was increased by BA in D/C-treated mice and HCC cells and inhibition of
      miR-21 significantly suppressed the pro-apoptotic effect of BA. miR-21 inhibitor
      attenuated BA-induced decrease of Sod2 and p53 inhibitor blocked BA-induced
      increase of miR-21. These results demonstrated that p53 is responsible for the
      anti-tumor effect of BA through up-regulation of p66(shc) and miR-21 and down
      regulation of Sod2 expression, leading to mitochondrial ROS accumulation and
      apoptosis. The p53-p66(shc)/miR-21-Sod2 signaling is critical for BA-inhibited
      tumor growth and cancer cell proliferation. 

PMID- 26222669
TI  - Short Synthesis of [5]- and [7]Phenacenes with Silyl Groups at the Axis
      Positions.
AB  - [5]Phenacene with trimethylsilyl groups at the axis positions was synthesized by
      the ruthenium-catalyzed direct C-H arylation of a 1-formyl-7-phenanthrene-derived
      aldimine, followed by sequential Wittig olefination and bismuth-catalyzed
      cyclization of the resulting vinyl ethers. By using the same synthetic building
      blocks and sequential Wittig olefination and photocyclization, the number of
      fused benzene rings was readily increased to seven to afford 3,12
      disilyl[7]phenacene. The introduction of silyl groups endowed the [n]phenacene
      frameworks with good solubility, as well as enabling further functionalization.
      The electronic structure of these new [n]phenacenes was determined by
      photophysical measurements and by density functional theory calculations, which
      clearly implied effective conjugation throughout the entire pi framework. 

PMID- 26222670
TI  - Iyengar Yoga Therapy Intervention for Ischial Pressure Ulcers in a Patient with
      Amyotrophic Lateral Sclerosis: A Case Study.
AB  - BACKGROUND: Although some research suggests that the formation of pressure ulcers
      is rare in patients with amyotrophic lateral sclerosis (ALS), several patients
      have nonetheless developed this problem. To date, however, no case reports in the
      literature have described patients with ALS who develop ischial pressure ulcers.
      Outside of the ALS literature, evidence suggests that ischial pressure ulcers
      frequently develop in wheelchair users and also in patients treated in various
      health care settings. CASE DESCRIPTION: A patient diagnosed with ALS reported the
      development of ischial pressure ulcers after consistent immobility for 1 year (32
      months after her ALS diagnosis). This patient, who was sitting on the wounds, was
      treated with ointment and morphine; the latter was ineffective in controlling the
      pain. Moving the patient from sitting to supine, lateral, or semilateral
      positions, either on the bed or wheelchair, to separate the ulcers from the
      surface of the chair or bed was deemed impossible because of exaggeration of
      other symptoms, including shortness of breath and pain in other parts of the
      body. A new method of postural alignment was developed to alleviate the pain
      associated with the pressure ulcer. This method, Iyengar yoga therapy, which uses
      props to reposition a patient, alleviated pain and healing of two pressure ulcers
      of the patient after 3 weeks of starting this intervention. CONCLUSION: Although
      the ischial pressure ulcers were successfully treated in a patient with ALS,
      further study is necessary to investigate the effectiveness of this postural
      alignment intervention in ALS and other patient populations for the management of
      ischial pressure ulcers.

PMID- 26222671
TI  - Differential role of gene hypermethylation in adenocarcinomas, squamous cell
      carcinomas and cervical intraepithelial lesions of the uterine cervix.
AB  - Cervical cancer is the third most common cancer in women worldwide. The
      hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell
      carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas
      (ADC) of the uterine cervix (total 181 lesions). Additionally human
      papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 hypermethylation were
      tested in ADC and the results were compared with those obtained previously by our
      group in SCC. P16, TSLC-1 and TSP-1 hypermethylation was more frequent in SCCs
      than in CINs. These percentages and the corresponding ones for EPB41L3, RASSF1
      and RASSF2 genes were also higher in SCCs than in ADCs, except for P16. The
      presence of HPV in ADCs was lower than reported previously in SCC and CIN.
      Patients with RASSF1A hypermethylation showed significantly longer disease-free
      survival (P = 0.015) and overall survival periods (P = 0.009) in ADC patients. To
      our knowledge, this is the first description of the EPB41L3 and RASSF2
      hypermethylation in ADCs. These results suggest that the involvement of DNA
      hypermethylation in cervical cancer varies depending on the histological type,
      which might contribute to explaining the different prognosis of patients with
      these types of tumors. 

PMID- 26222672
TI  - Selective fermentation of carbohydrate and protein fractions of Scenedesmus, and
      biohydrogenation of its lipid fraction for enhanced recovery of saturated fatty
      acids.
AB  - Biofuels derived from microalgae have promise as carbon-neutral replacements for
      petroleum. However, difficulty extracting microalgae-derived lipids and the co
      extraction of non-lipid components add major costs that detract from the benefits
      of microalgae-based biofuel. Selective fermentation could alleviate these
      problems by managing microbial degradation so that carbohydrates and proteins are
      hydrolyzed and fermented, but lipids remain intact. We evaluated selective
      fermentation of Scenedesmus biomass in batch experiments buffered at pH 5.5, 7,
      or 9. Carbohydrates were fermented up to 45% within the first 6 days, protein
      fermentation followed after about 20 days, and lipids (measured as fatty acid
      methyl esters, FAME) were conserved. Fermentation of the non-lipid components
      generated volatile fatty acids, with acetate, butyrate, and propionate being the
      dominant products. Selective fermentation of Scenedesmus biomass increased the
      amount of extractable FAME and the ratio of FAME to crude lipids. It also led to
      biohydrogenation of unsaturated FAME to more desirable saturated FAME (especially
      to C16:0 and C18:0), and the degree of saturation was inversely related to the
      accumulation of hydrogen gas after fermentation. Moreover, the microbial
      communities after selective fermentation were enriched in bacteria from families
      known to perform biohydrogenation, i.e., Porphyromonadaceae and Ruminococcaceae.
      Thus, this study provides proof-of-concept that selective fermentation can
      improve the quantity and quality of lipids that can be extracted from
      Scenedesmus.

PMID- 26222673
TI  - Integrating Molecular Subclassification of Medulloblastomas into Routine Clinical
      Practice: A Simplified Approach.
AB  - Medulloblastoma (MB) is composed of four molecular subgroups viz. WNT, SHH,
      groups 3 and 4, identified using various high-throughput methods. Translation of
      this molecular data into pathologist-friendly techniques that would be applicable
      in laboratories all over the world is a major challenge. Ninety-two MBs were
      analyzed using a panel of 10 IHC markers, real-time PCR for mRNA and miRNA
      expression, and FISH for MYC amplification. beta-catenin, GAB1 and YAP1 were the
      only IHC markers of utility in classification of MBs into three subgroups viz.
      WNT (9.8%), SHH (45.6%) and non-WNT/SHH (44.6%). mRNA expression could further
      classify some non-WNT/SHH tumors into groups 3 and 4. This, however, was
      dependent on integrity of RNA extracted from FFPE tissue. MYC amplification was
      seen in 20% of non-WNT/SHH cases and was associated with the worst prognosis. For
      routine diagnostic practice, we recommend classification of MBs into three
      subgroups: WNT, SHH and non-WNT/SHH, with supplementation by prognostic markers
      like MYC for non-WNT/SHH tumors. Using this panel, we propose a new three-tier
      risk stratification system for MBs. Molecular subgrouping with this limited panel
      is rapid, economical, works well on FFPE tissue and is reliable as it correlates
      significantly with clinicopathological parameters and patient survival.

PMID- 26222674
TI  - Living with Lymphangioleiomyomatosis: An Anesthesiologist's Experience.

PMID- 26222675
TI  - Multidisciplinary rehabilitation for children with brain tumors: A systematic
      review.
AB  - BACKGROUND: There is an increasing need to assess the evidence of a
      multidisciplinary approach for both short-term and long-term management of
      neurological sequelae arising from the diagnosis and treatment of brain tumors in
      childhood. METHODS: We performed a systematic review of the evidence base for
      multidisciplinary paediatric brain tumor rehabilitation using seven databases.
      PRISMA guidelines were adhered to and the review was registered with the PROSPERO
      international prospective register of systematic reviews (registration number
      CRD42014015070). RESULTS: The literature search identified 3,061 results. Three
      service evaluations were included. The review identified limited evidence in
      favor of multidisciplinary rehabilitation for children with brain tumors. Due to
      the lack of controlled trial data and heterogeneity of the interventions and
      outcome measures, no meta-analysis could be performed. CONCLUSIONS: Studies
      utilising a coordinated multi-centre approach with standardized outcome measures
      are recommended in order to enable robust assessment of the efficacy of
      multidisciplinary rehabilitation services.

PMID- 26222676
TI  - Eugenics and Mandatory Informed Prenatal Genetic Testing: A Unique Perspective
      from China.
AB  - The application of genetic technologies in China, especially in the area of
      prenatal genetic testing, is rapidly increasing in China. In the wealthy regions
      of China, prenatal genetic testing is already very widely adopted. We argue that
      the government should actively promote prenatal genetic testing to the poor areas
      of the country. In fact, the government should prioritize resources first to make
      prenatal genetic testing a standard routine care with an opt-out model in these
      area. Healthcare professions would be required to inform pregnant women about the
      availability of genetic testing and provide free testing on a routine basis
      unless the parents choose not to do so. We argue that this proposal will allow
      parents to make a more informed decision about their reproductive choices.
      Secondarily, this proposal will attract more healthcare professionals and other
      healthcare resources to improve the healthcare infrastructures in the less
      developed regions of the country. This will help to reduce the inequity of
      accessing healthcare services between in different regions of China. We further
      argue that this policy proposal is not practicing eugenics.

PMID- 26222677
TI  - Anti-Resorptive Functions of Poly(ethylene sodium phosphate) on Human
      Osteoclasts.
AB  - Osteoporosis involves hyperactive osteoclasts. A large number of current drugs
      result in side effects affecting their efficacy in the clinic. Polyphosphoesters
      are unique polymeric biomaterials because of their biocompatibility,
      biodegradability, and bone affinity. We studied the viability and ability of
      human osteoclasts to resorb bone when dosed with poly(ethylene sodium phosphate)
      (PEP.Na). This did not trigger any change in osteoblast cell viability, however
      the polymer diminished human osteoclasts and their ability to resorb bone at
      concentrations as low as 10(-4) m . mL(-1). This is the first report to validate
      the possibility of using polyphosphoesters for selective inhibition of human
      osteoclast functions, indicating its potential to be used as an effective polymer
      prodrug for treatment of osteoporosis.

PMID- 26222678
TI  - New furoquinoline alkaloid and flavanone glycoside derivatives from the leaves of
      Oricia suaveolens and Oricia renieri (Rutaceae).
AB  - Fractionation of the methanol extract of the leaves of Oricia renieri and Oricia
      suaveolens (Rutaceae) led to the isolation of 13 compounds including the hitherto
      unknown furoquinoline alkaloid named 6,7-methylenedioxy-5-hydroxy-8-methoxy
      dictamnine (1) and a flavanone glycoside named 5-hydroxy-4'-methoxy-7-O-[alpha-L
      rhamnopyranosyl(1'''->5")-beta-D-apiofuranosyl]-flavanoside (2), together with 11
      known compounds (3-13). The structures of the compounds were determined by
      comprehensive analyses of their 1D and 2D NMR, mass spectral data and comparison.
      All compounds isolated were examined for their activity against human carcinoma
      cell lines. The alkaloids 1, 5, 12, 13 and the phenolic 2, 8, 11 tested compounds
      exhibited non-selective moderate cytotoxic activity with IC50 8.7-15.9 MUM
      whereas compounds 3, 4, 6, 7, 9 and 10 showed low activity.

PMID- 26222679
TI  - Differential Expression and Enzymatic Activity of DPPIV/CD26 Affects Migration
      Ability of Cervical Carcinoma Cells.
AB  - Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein that
      inactivates or degrades some bioactive peptides and chemokines. For this reason,
      it regulates cell proliferation, migration and adhesion, showing its role in
      cancer processes. This enzyme is found mainly anchored onto the cell membrane,
      although it also has a soluble form, an enzymatically active isoform. In the
      present study, we investigated DPPIV/CD26 activity and expression in cervical
      cancer cell lines (SiHa, HeLa and C33A) and non-tumorigenic HaCaT cells. The
      effect of the DPPIV/CD26 inhibitor (sitagliptin phosphate) on cell migration and
      adhesion was also evaluated. Cervical cancer cells and keratinocytes exhibited
      DPPIV/CD26 enzymatic activity both membrane-bound and in soluble form. DPPIV/CD26
      expression was observed in HaCaT, SiHa and C33A, while in HeLa cells it was
      almost undetectable. We observed higher migratory capacity of HeLa, when compared
      to SiHa. But in the presence of sitagliptin SiHa showed an increase in migration,
      indicating that, at least in part, cell migration is regulated by DPPIV/CD26
      activity. Furthermore, in the presence of sitagliptin phosphate, SiHa and HeLa
      cells exhibited a significant reduction in adhesion. However this mechanism seems
      to be mediated independent of DPPIV/CD26. This study demonstrates, for the first
      time, the activity and expression of DPPIV/CD26 in cervical cancer cells and the
      effect of sitagliptin phosphate on cell migration and adhesion. 

PMID- 26222681
TI  - Enhanced Stability of Aluminum Nanoparticle-Doped Organic Solar Cells.
AB  - Enhancement of the stability of bulk heterojunction (BHJ) organic photovoltaic
      (OPV) devices is reported by the addition of surfactant-free aluminum (Al)
      nanoparticles (NPs) into the photoactive layer. The universality of the effect is
      demonstrated for two different BHJ systems, namely, the well-studied poly(3
      hexylthiophene-2,5-diyl):phenyl-C61-butyric acid methyl ester (P3HT:PCBM) as well
      as the high efficient poly[N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2
      thienyl-2',1',3'-benzothiadiazole)]:[6,6]-phenyl-C71-butyric acid methyl ester
      (PCDTBT:PC71BM). It is shown that the lifetime of the devices with Al NPs,
      operating under continuous one-sun illumination in ambient conditions, is more
      than three times longer compared to the reference devices. Using complementary
      analytical techniques for in situ studies, we have explored the underlying
      mechanisms behind the observed stability improvement in the case of the P3HT:PCBM
      system. In particular, laser-induced fluorescence (LIF), photoluminescence decay
      and Fourier transform infrared (FTIR) spectroscopy experiments were performed and
      complemented with device degradation electrical measurements. It is found that
      the embedded Al NPs act as performance stabilizers, giving rise to enhanced
      structural stability of the active blend. Furthermore, it is revealed that the
      observed improvement can also be ascribed to NP-mediated mitigation of the photo
      oxidation effect. This study addresses a major issue in OPV devices, that is,
      photoinduced stability, indicating that the exploitation of Al NPs could be a
      successful approach toward fabricating OPVs exhibiting long-term operating
      lifetimes. 

PMID- 26222680
TI  - Inferring Population Genetic Structure in Widely and Continuously Distributed
      Carnivores: The Stone Marten (Martes foina) as a Case Study.
AB  - The stone marten is a widely distributed mustelid in the Palaearctic region that
      exhibits variable habitat preferences in different parts of its range. The
      species is a Holocene immigrant from southwest Asia which, according to fossil
      remains, followed the expansion of the Neolithic farming cultures into Europe and
      possibly colonized the Iberian Peninsula during the Early Neolithic (ca. 7,000
      years BP). However, the population genetic structure and historical biogeography
      of this generalist carnivore remains essentially unknown. In this study we have
      combined mitochondrial DNA (mtDNA) sequencing (621 bp) and microsatellite
      genotyping (23 polymorphic markers) to infer the population genetic structure of
      the stone marten within the Iberian Peninsula. The mtDNA data revealed low
      haplotype and nucleotide diversities and a lack of phylogeographic structure,
      most likely due to a recent colonization of the Iberian Peninsula by a few mtDNA
      lineages during the Early Neolithic. The microsatellite data set was analysed
      with a) spatial and non-spatial Bayesian individual-based clustering (IBC)
      approaches (STRUCTURE, TESS, BAPS and GENELAND), and b) multivariate methods
      [discriminant analysis of principal components (DAPC) and spatial principal
      component analysis (sPCA)]. Additionally, because isolation by distance (IBD) is
      a common spatial genetic pattern in mobile and continuously distributed species
      and it may represent a challenge to the performance of the above methods, the
      microsatellite data set was tested for its presence. Overall, the genetic
      structure of the stone marten in the Iberian Peninsula was characterized by a NE
      SW spatial pattern of IBD, and this may explain the observed disagreement between
      clustering solutions obtained by the different IBC methods. However, there was
      significant indication for contemporary genetic structuring, albeit weak, into at
      least three different subpopulations. The detected subdivision could be
      attributed to the influence of the rivers Ebro, Tagus and Guadiana, suggesting
      that main watercourses in the Iberian Peninsula may act as semi-permeable
      barriers to gene flow in stone martens. To our knowledge, this is the first
      phylogeographic and population genetic study of the species at a broad regional
      scale. We also wanted to make the case for the importance and benefits of using
      and comparing multiple different clustering and multivariate methods in spatial
      genetic analyses of mobile and continuously distributed species. 

PMID- 26222682
TI  - Bioorthogonal SERS Nanoprobes for Mulitplex Spectroscopic Detection, Tumor Cell
      Targeting, and Tissue Imaging.
AB  - A surface-enhanced Raman scattering (SERS) technique shows extraordinary features
      for a range of biological and biomedical applications. Herein, a series of novel
      bioorthogonal SERS nanoprobes were constructed with Gold nanoflower (AuNF) and
      Raman reporters, the signals of which were located in a Raman-silent region of
      biological samples. AS1411 aptamer was also co-conjugated with AuNF through a
      self-assembled monolayer coverage strategy. Multiplex SERS imaging using these
      nanoprobes with three different bioorthogonal small-molecule Raman reporters is
      successfully achieved with high multiplexing capacity in a biologically Raman
      silent region. These Raman nanoprobes co-conjugated with AS1411 showed high
      affinity for tumor cells with overexpressed nucleolin and can be used for
      selective tumor cell screening and tissue imaging. 

PMID- 26222683
TI  - Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up
      Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-kappaB
      Pathways.
AB  - Acute renal failure is a serious complication of the anticancer drug cisplatin.
      The potential role of baicalein, a naturally occurring bioflavonoid on cisplatin
      induced renal injury is unknown. Here, we assessed the effect of baicalein
      against a murine model of cisplatin-induced acute renal failure and investigated
      the underlying possible mechanisms. Renal function, kidney histology,
      inflammation, oxidative stress, renal mitochondrial function, proteins involved
      in apoptosis, nuclear translocation of Nrf2 and effects on intracellular
      signaling pathways such as MAPKs, and NF-kappaB were assessed. Pretreatment with
      baicalein ameliorated the cisplatin-induced renal oxidative stress, apoptosis and
      inflammation and improved kidney injury and function. Baicalein inhibited the
      cisplatin-induced expression of iNOS, TNF-alpha, IL-6 and mononuclear cell
      infiltration and concealed redox-sensitive transcription factor NF-kappaB
      activation via reduced DNA-binding activity, IkappaBalpha phosphorylation and p65
      nuclear translocation in kidneys. Further studies demonstrated baicalein markedly
      attenuated cisplatin-induced p38 MAPK, ERK1/2 and JNK phosphorylation in kidneys.
      Baicalein also restored the renal antioxidants and increased the amount of total
      and nuclear accumulation of Nrf2 and downstream target protein, HO-1 in kidneys.
      Moreover, baicalein preserved mitochondrial respiratory enzyme activities and
      inhibited cisplatin-induced apoptosis by suppressing p53 expression, Bax/Bcl-2
      imbalance, cytochrome c release and activation of caspase-9, caspase-3 and PARP.
      Our findings suggest that baicalein ameliorates cisplatin-induced renal damage
      through up-regulation of antioxidant defense mechanisms and down regulation of
      the MAPKs and NF-kappaB signaling pathways. 

PMID- 26222685
TI  - Deaths: Leading Causes for 2011.
AB  - OBJECTIVES: This report presents final 2011 data on the 10 leading causes of
      death in the United States by age, sex, race, and Hispanic origin. Leading causes
      of infant, neonatal, and postneonatal death are also presented. This report
      supplements ''Deaths: Final Data for 2011,'' the National Center for Health
      Statistics' annual report of final mortality statistics. METHODS: Data in this
      report are based on information from all death certificates filed in the 50
      states and the District of Columbia in 2011. Causes of death classified by the
      International Classification of Diseases, 10th Revision (ICD-10) are ranked
      according to the number of deaths assigned to rankable causes. Cause-of-death
      statistics are based on the underlying cause of death. RESULTS: In 2011, the 10
      leading causes of death were, in rank order: Diseases of heart; Malignant
      neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases;
      Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus;
      Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and
      Intentional self-harm (suicide). They accounted for 74% of all deaths occurring
      in the United States. Differences in the rankings are evident by age, sex, race,
      and Hispanic origin. Leading causes of infant death for 2011 were, in rank order:
      Congenital malformations, deformations and chromosomal abnormalities; Disorders
      related to short gestation and low birth weight, not elsewhere classified; Sudden
      infant death syndrome; Newborn affected by maternal complications of pregnancy;
      Accidents (unintentional injuries); Newborn affected by complications of
      placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress
      of newborn; Diseases of the circulatory system; and Neonatal hemorrhage.
      Important variations in the leading causes of infant death are noted for the
      neonatal and postneonatal periods.

PMID- 26222684
TI  - IL-10-592 A/C polymorphisms is associated with EBV-HLH in Chinese children.
AB  - OBJECTIVES: The aim of this study is to investigate the relationship between
      cytokine gene polymorphisms and Epstein-Barr virus-associated hemophagocytic
      lymphohistiocytosis (EBV-HLH) in children, and to further reveal the possible
      mechanisms of EBV-HLH. METHODS: Forty-one patients with EBV-HLH, 70 patients with
      infectious mononucleosis (IM), and 170 EBV-seropositive healthy children were
      evaluated. Gene polymorphism typing was performed by a polymerase chain reaction
      with a sequence-specific primer of a commercially available cytokine genotyping
      kit. Comparison of cytokine gene polymorphisms between EBV-HLH, IM patients, and
      healthy controls was analyzed statistically using Chi-square test or Fisher's
      exact test. RESULTS: The frequencies of IL-10-592 C allele or IL-10-592 CC
      genotype were significantly higher in patients with EBV-HLH than in IM and
      healthy children (P < 0.001), but no significant difference was observed between
      IM and healthy children. CONCLUSION: IL-10-592 locus gene polymorphism is
      associated with the development of EBV-HLH in Chinese children.

PMID- 26222686
TI  - Metabolic Plasticity and Inter-Compartmental Interactions in Rice Metabolism: An
      Analysis from Reaction Deletion Study.
AB  - More than 20% of the total caloric intake of human population comes from rice.
      The expression of rice genes and hence, the concentration of enzymatic proteins
      might vary due to several biotic and abiotic stresses. It in turn, can influence
      the overall metabolism and survivability of rice plant. Thus, understanding the
      rice cellular metabolism, its plasticity and potential readjustments under
      different perturbations can help rice biotechnologists to design efficient rice
      cultivars. Here, using the flux balance analysis (FBA) method, with the help of
      in-silico reaction deletion strategy, we study the metabolic plasticity of genome
      scale metabolic model of rice leaf. A set of 131 reactions, essential for the
      production of primary biomass precursors is identified; deletion of any of them
      can inhibit the overall biomass production. Usability Index (IU) for the rest of
      the reactions are estimated and based on this parameter, they are classified into
      three categories-maximally-favourable, quasi-favourable and unfavourable for the
      primary biomass production. The lower value of 1 - IU of a reaction suggests that
      the cell cannot easily bypass it for biomass production. While some of the
      alternative paths are energetically equally efficient, others demand for higher
      photon. The variations in (i) ATP/NADPH ratio, (ii) exchange of metabolites
      through chloroplastic transporters and (iii) total biomass production are also
      presented here. Mutual metabolic dependencies of different cellular compartments
      are also demonstrated. 

PMID- 26222687
TI  - Magnetic scavengers as carriers of analytes for flowing atmospheric pressure
      afterglow mass spectrometry (FAPA-MS).
AB  - In this paper, a procedure for the preconcentration and transport of mixtures of
      acids, bases, and drug components to a mass spectrometer using magnetic
      scavengers is presented. Flowing atmospheric pressure afterglow mass spectrometry
      (FAPA-MS) was used as an analytical method for identification of the compounds by
      thermal desorption from the scavengers. The proposed procedure is fast and cheap,
      and does not involve time-consuming purification steps. The developed methodology
      can be applied for trapping harmful substances in minute quantities, to transport
      them to specialized, remotely located laboratories. 

PMID- 26222689
TI  - Electron Spin Density on the N-Donor Atoms of Cu(II)-(Bis)oxamidato Complexes As
      Probed by a Pulse ELDOR Detected NMR.
AB  - We have applied the pulse ELDOR detected NMR (EDNMR) technique to determine the
      tensors of the transferred Cu (S = 1/2) - (14)N (I = 1) hyperfine (HF)
      interaction in single crystals of diamagnetically diluted mononuclear o
      phenylenebis(N(R)-oxamide) complexes of [(n)Bu4N]2[Cu(opboR2)] (R = Et 1, (n)Pr
      2) (1%) in a host lattice of [(n)Bu4N]2[Ni(opboR2)] (R = Et 3, (n)Pr 4) (99%)
      (1@3 and 2@4)). To facilitate the analysis of our EDNMR data and to analyze
      possible manifestations of the nuclear quadrupole interaction in the EDNMR
      spectra, we have treated a model electron-nuclear system of the coupled S = 1/2
      and I = 1 spins using the spin density matrix formalism. It appears that this
      interaction yields a peculiar asymmetry of the EDMR spectra that manifests not
      only in the shift of the positions of the EDNMR lines that correspond to the
      forbidden EPR transitions, as expected, but also in the intensities of the EDNMR
      lines. The symmetric shape of the experimental spectra suggests the conclusion
      that, in the studied complexes, the quadrupole interaction is negligible. This
      has simplified the analysis of the spectra. The HF tensors of all four N donor
      atoms could be accurately determined. On the basis of the HF tensors, an estimate
      of the spin density transferred from the central paramagnetic Cu(II) ion to the N
      donor atoms reveals its unequal distribution. We discuss possible implications of
      our estimates for the magnetic exchange paths and interaction strengths in
      respective trinuclear complexes [Cu3(opboR2) (pmdta)2](NO3)2 (R = Et 6, (n)Pr 7).

PMID- 26222688
TI  - Gender and Obesity Specific MicroRNA Expression in Adipose Tissue from Lean and
      Obese Pigs.
AB  - Obesity is a complex condition that increases the risk of life threatening
      diseases such as cardiovascular disease and diabetes. Studying the gene
      regulation of obesity is important for understanding the molecular mechanisms
      behind the obesity derived diseases and may lead to better intervention and
      treatment plans. MicroRNAs (miRNAs) are short non-coding RNAs regulating target
      mRNA by binding to their 3'UTR. They are involved in numerous biological
      processes and diseases, including obesity. In this study we use a mixed breed pig
      model designed for obesity studies to investigate differentially expressed miRNAs
      in subcutaneous adipose tissue by RNA sequencing (RNAseq). Both male and female
      pigs are included to explore gender differences. The RNAseq study shows that the
      most highly expressed miRNAs are in accordance with comparable studies in pigs
      and humans. A total of six miRNAs are differentially expressed in subcutaneous
      adipose tissue between the lean and obese group of pigs, and in addition gender
      specific significant differential expression is observed for a number of miRNAs.
      The differentially expressed miRNAs have been verified using qPCR. The results of
      these studies in general confirm the trends found by RNAseq. Mir-9 and mir-124a
      are significantly differentially expressed with large fold changes in
      subcutaneous adipose tissue between lean and obese pigs. Mir-9 is more highly
      expressed in the obese pigs with a fold change of 10 and a p-value < 0.001. Mir
      124a is more highly expressed in the obese pigs with a fold change of 114 and a p
      value < 0.001. In addition, mir-124a is significantly higher expressed in
      abdominal adipose tissue in male pigs with a fold change of 119 and a p-value <
      0.05. Both miRNAs are also significantly higher expressed in the liver of obese
      male pigs where mir-124a has a fold change of 12 and mir-9 has a fold change of
      1.6, both with p-values < 0.05. 

PMID- 26222690
TI  - Soil Nitrogen-Cycling Responses to Conversion of Lowland Forests to Oil Palm and
      Rubber Plantations in Sumatra, Indonesia.
AB  - Rapid deforestation in Sumatra, Indonesia is presently occurring due to the
      expansion of palm oil and rubber production, fueled by an increasing global
      demand. Our study aimed to assess changes in soil-N cycling rates with conversion
      of forest to oil palm (Elaeis guineensis) and rubber (Hevea brasiliensis)
      plantations. In Jambi Province, Sumatra, Indonesia, we selected two soil
      landscapes - loam and clay Acrisol soils - each with four land-use types: lowland
      forest and forest with regenerating rubber (hereafter, "jungle rubber") as
      reference land uses, and rubber and oil palm as converted land uses. Gross soil-N
      cycling rates were measured using the 15N pool dilution technique with in-situ
      incubation of soil cores. In the loam Acrisol soil, where fertility was low,
      microbial biomass, gross N mineralization and NH4+ immobilization were also low
      and no significant changes were detected with land-use conversion. The clay
      Acrisol soil which had higher initial fertility based on the reference land uses
      (i.e. higher pH, organic C, total N, effective cation exchange capacity (ECEC)
      and base saturation) (P<=0.05-0.09) had larger microbial biomass and NH4+
      transformation rates (P<=0.05) compared to the loam Acrisol soil. Conversion of
      forest and jungle rubber to rubber and oil palm in the clay Acrisol soil
      decreased soil fertility which, in turn, reduced microbial biomass and
      consequently decreased NH4+ transformation rates (P<=0.05-0.09). This was further
      attested by the correlation of gross N mineralization and microbial biomass N
      with ECEC, organic C, total N (R=0.51-0. 76; P<=0.05) and C:N ratio (R=-0.71 - 
      0.75, P<=0.05). Our findings suggest that the larger the initial soil fertility
      and N availability, the larger the reductions upon land-use conversion. Because
      soil N availability was dependent on microbial biomass, management practices in
      converted oil palm and rubber plantations should focus on enriching microbial
      biomass.

PMID- 26222691
TI  - Inadequate Models of Adolescent Substance Use Prevention: Looking for Options to
      Promote Pro-Social Change and Engagement.
AB  - In the adolescent substance use prevention two competing models can be found:
      negative and positive. The negative model is entirely focused on risks and
      problems that young people should avoid. The positive model goes beyond that
      problem-oriented perspective and calls for positive youth growth and development.
      Both models of prevention seems to be inadequate to address effectively the
      challenging problem of adolescent substance use associated consequences. Both
      models are in fact flawed, but in different ways. Old, negative model neglects
      the power of individual strengths and ecological developmental assets, while new,
      positive model is often instrumentally used by politicians and other stakeholders
      for completely different goals than an informed, science-based prevention. As a
      result many substance use prevention programs implemented at schools and in
      communities are neither theoretically nor empirically informed. In order to
      address these flaws, the model of balanced prevention was outlined. It posits
      that triple well informed efforts are needed to achieve both specific substance
      use prevention goals and youth personal/social development. These efforts include
      protection building, risks reducing and individual assets development support.
      The proposed model is an ongoing work in progress. It can be considered as an
      encouragement for international dialogue to build a balanced conceptual
      foundation for adolescent substance use prevention. 

PMID- 26222693
TI  - Geleganidines A-C, Unusual Monoterpenoid Indole Alkaloids from Gelsemium elegans.
AB  - The first rotameric monoterpenoid indole alkaloids (MIAs), 1a and 1b, and two
      unusual dimeric MIAs, 2 and 3, with new dimerization patterns, together with
      their putative biosynthetic intermediates 4-7, were isolated from the roots of
      Gelsemium elegans. Compounds 2 and 3 represent the first natural aromatic azo-
      and the first urea-linked dimeric MIAs, respectively. Their structures and
      absolute configurations were elucidated by means of NMR spectroscopy, single
      crystal X-ray diffraction, and electronic circular dichroism data analyses. The
      interconverting mechanism of rotamers 1a and 1b was studied by density functional
      theory computation. Compounds 2 and 3 showed moderate cytotoxic activity against
      MCF-7 and PC-12 cells, respectively. In addition, a plausible biosynthesis
      pathway for the new alkaloids was proposed on the basis of the coexistence of
      their biosynthetic precursors. 

PMID- 26222692
TI  - Ketamine/Xylazine-Induced Corneal Damage in Mice.
AB  - PURPOSE: We have observed that the commonly used ketamine/xylazine anesthesia mix
      can induce a focally severe and permanent corneal opacity. The purpose of this
      study was to establish the clinical and histological features of this deleterious
      side effect, its sensitivity with respect to age and anesthesia protocol, and
      approaches for avoiding it. METHODS: Young C57BL/6J, C57BLKS/J, and SJL/J mice
      were treated with permutations of anesthesia protocols and compared using slit
      lamp exams, optical coherence tomography, histologic analyses, and telemetric
      measurements of body temperature. RESULTS: Ketamine/xylazine induces corneal
      damage in mice with a variable frequency. Among 12 experimental cohorts, corneal
      damage associated with ketamine/xylazine was observed in 9 of them. Despite
      various treatments to avoid corneal dehydration during anesthesia, the frequency
      of corneas experiencing damage among responding cohorts was 42% (26% inclusive of
      all cohorts), which is significantly greater than the natural prevalence (5%).
      The damage was consistent with band keratopathy. It appeared as a white or gray
      horizontal band located proximal to the pupil and was positive for subepithelial
      calcium deposition with von Kossa stain. CONCLUSIONS: The sum of our clinical and
      histological observations is consistent with ketamine/xylazine-induced band
      keratopathy in mice. This finding is relevant for mouse studies involving the eye
      and/or vision-dependent behavioral assays, which would both be prone to artifact
      without appreciation of the damage caused by ketamine/xylazine anesthesia. Use of
      yohimbine is suggested as a practical means of avoiding this complication.

PMID- 26222694
TI  - Frequency of the p.Gly262Asp mutation in congenital Factor X deficiency.
AB  - INTRODUCTION: Congenital factor X (FX) deficiency is a rare bleeding disorder
      inherited as an autosomal recessive trait with an incidence of 1 : 500 000-1 000
      000. A total or partial deficiency of FX causes an impairment of clot formation,
      leading to a haemorrhagic disease, which manifests with bleeding symptoms of
      different severity, also unprovoked. AIM: We analysed the clinical
      manifestations, laboratory phenotype and genotype in 12 patients from Turkey
      affected with severe FX deficiency. METHODS: Prothrombin time (PT), activated
      partial thromboplastin time (APTT), FX activity (FX:C) and FX antigen level
      (FX:Ag) were measured, and mutation analysis was performed for all patients.
      RESULTS: The most frequent bleeding episodes in patients were epistaxis and easy
      bruising (11/12, 91%), followed by haemarthroses (10/12, 83%). FX:C was <1% in 11
      patients, and 4% in one. FX:Ag was reduced in all patients, consistent with type
      II deficiency. Direct sequencing of the factor X gene (F10) identified two
      different mutations: the novel 33 bp in-frame deletion p.Thr176_Gln186,
      c.526_558del, which seems to be associated with milder bleeding symptoms and the
      c.785G>A, p.Gly262Asp missense mutation (previously reported as Gly222Asp), which
      is associated with severe bleeding symptoms. CONCLUSION: The p.Gly262Asp missense
      mutation was identified in 11 of the 12 patients in this study. Previously
      published cases on the same p.Gly262Asp mutation were Iranian patients
      originating from the border between Turkey and Iran suggesting that this mutation
      may be candidate as a good tool for mutational screening analysis in this area.

PMID- 26222697
TI  - Correction: Establishment and Characterization of PCL12, a Novel CD5+ Chronic
      Lymphocytic Leukaemia Cell Line.

PMID- 26222696
TI  - BAI1-Associated Protein 2-Like 1 (BAIAP2L1) Is a Potential Biomarker in Ovarian
      Cancer.
AB  - Brain-specific angiogenesis inhibitor 1 (BAI1)-associated protein 2-like 1
      (BAIAP2L1), also known as insulin receptor tyrosine kinase substrate (IRTKS), is
      involved in plasma membrane protrusion and actin formation during cell
      morphogenesis and migration. BAIAP2L1 is recently reported to promote cell
      proliferation through activation of the EGFR-ERK pathway in hepatocellular
      carcinoma. In this study, we report the first comprehensive study of BAIAP2L1
      upregulation in human ovarian cancer. Upregulation of BAIAP2L1 in ovarian tumors
      was first found during RNA screening and confirmed by immunohistochemical studies
      on ovarian cancers and other cancer types. Significant upregulation of BAIAP2L1
      in ovarian cancer was validated by analyzing multiple independent cohorts in
      publicly available data sets. Furthermore, BAIAP2L1 protein expression in
      metastatic lesions was higher than the corresponding primary tumors. Functional
      assays in ovarian cancer cells revealed that BAIAP2L1 is involved in promoting
      cell proliferation and avoiding apoptosis. In conclusion, results of this study
      not only indicate that BAIAP2L1 can be used as a biomarker for human ovarian
      cancer but also reveal its role in cancer biology. Further elucidation of the
      role of BAIAP2L1 in context of the insulin receptor signaling pathways of cancer
      cells is warranted for developing cancer therapeutics by targeting cancer
      specific metabolism. 

PMID- 26222698
TI  - Disturbed Intracardiac Flow Organization After Atrioventricular Septal Defect
      Correction as Assessed With 4D Flow Magnetic Resonance Imaging and Quantitative
      Particle Tracing.
AB  - OBJECTIVES: Four-dimensional (3 spatial directions and time) velocity-encoded
      flow magnetic resonance imaging with quantitative particle tracing analysis
      allows assessment of left ventricular (LV) blood flow organization. Corrected
      atrioventricular septal defect (AVSD) patients have an abnormal left
      atrioventricular valve shape. We aimed to analyze flow organization in corrected
      AVSD patients and healthy controls. METHODS: A total of 32 patients (age, 25 +/-
      14 years), 21 after partial AVSD correction and 11 after complete/intermediate
      AVSD correction, and 30 healthy volunteers (26 +/- 12 years) underwent whole
      heart four-dimensional velocity-encoded flow magnetic resonance imaging. Particle
      tracing in the 16-segment LV cavity model was used to quantitatively evaluate
      blood flow organization discriminating multiple components. RESULTS: Patients
      showed a smaller percentage of direct flow compared with controls (30% +/- 9% vs
      44% +/- 11%; P < 0.001). In patients, more inflow was observed in the basal
      inferior segment (22% +/- 11% vs controls, 17% +/- 5%; P = 0.005), with less
      direct but more retained inflow (ie, part of inflow that is not ejected from LV
      in subsequent systole). In patients, more inflow reached the midventricular level
      (68% +/- 13% vs controls, 58% +/- 9%; P < 0.001), most notably as retained inflow
      in the lateral segments. Subsequently, in patients, more (mostly retained) inflow
      reached the apex (23% +/- 13% vs 14% +/- 7%; P < 0.001), which correlated with
      early peak filling velocity (r = 0.637, P < 0.001). Patients with a corrected
      complete or intermediate AVSD presented with less direct flow (24% +/- 8% vs 33%
      +/- 8%; P = 0.003) and more apical inflow (30% +/- 14% vs 18% +/- 12%; P = 0.014)
      compared with a corrected partial AVSD. CONCLUSION: Multicomponent particle
      tracing combined with 16-segment analysis quantitatively demonstrated altered LV
      flow organization after AVSD correction, with less direct and more retained
      inflow in apical and lateral LV cavity segments, which may contribute to
      decreased cardiac pumping efficiency.

PMID- 26222699
TI  - Educational outcomes associated with childhood obesity in the United States:
      cross-sectional results from the 2011-2012 National Survey of Children's Health.
AB  - BACKGROUND: Past research examining the effects of childhood obesity has largely
      focused on its projected effects into adulthood. However, there is emerging
      evidence that childhood obesity may have more immediate effects on school-related
      outcomes. We examine a range of educational attainment indicators to examine the
      possible pathway between obesity status and academic performance, while
      investigating the proximal effects of childhood obesity on health and utilization
      of health services, and whether these variables attenuate the relationship
      between obesity status and educational outcomes. METHODS: Data for the current
      study come from the 2011-2012 National Survey of Children's Health, which details
      the impacts of childhood obesity on a range of outcomes among a nationally
      representative sample of children and adolescents aged 10-17 years (N=45,255).
      Educational outcomes (school absences, school problems, repeating a grade and
      school engagement) were modeled by logistic regression as a function of BMI,
      overall health status, health care utilization, and a range of sociodemographic
      variables. RESULTS: BMI status was significantly associated with all educational
      outcomes (p<0.001 for all), overall health status (p<0.001), and health care
      utilization (p=0.016). Prior to adjustment for covariates, obese children were
      significantly more likely to have school absences and school problems, to repeat
      a grade, and to have lower school engagement than non-overweight children. After
      adjustment for sociodemographic and health/healthcare variables, these outcomes
      remained significant for all but repeating a grade. The odds of having school
      problems, repeating a grade, and low school engagement that were associated with
      obesity were attenuated by the addition of sociodemographic variables into the
      model, while the addition of health and health care variables in the model
      decreased the odds of school absences. CONCLUSIONS: This study provides evidence
      that increased weight status in children is associated with poorer educational
      outcomes. While recognizing that these are cross-sectional data, we suggest that
      1) health-related and sociodemographic factors should be a focus point of
      intervention, and 2) a socio-structural approach including Coordinated School
      Health intervention is crucial to reducing childhood obesity and improving
      educational outcomes in this population.

PMID- 26222700
TI  - Increased serum bile acid concentration following low-dose chronic administration
      of thioacetamide in rats, as evidenced by metabolomic analysis.
AB  - A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based
      metabolomics approach was employed to identify endogenous metabolites as
      potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and
      30mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague
      Dawley (SD) rats for 28days. We then conducted untargeted analyses of endogenous
      serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA)
      was performed on serum and liver samples to evaluate metabolites associated with
      TAA-induced perturbation. TAA administration resulted in altered levels of bile
      acids, acyl carnitines, and phospholipids in serum and in the liver. We
      subsequently demonstrated and confirmed the occurrence of compromised bile acid
      homeostasis. TAA treatment significantly increased serum levels of conjugated
      bile acids in a dose-dependent manner, which correlated well with toxicity.
      However, hepatic levels of these metabolites were not substantially changed. Gene
      expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and
      Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4
      were increased. Decreased levels of Ntcp, Oatp1b2, and Ostalpha proteins in the
      liver were confirmed by western blot analysis. These results suggest that serum
      bile acids might be increased due to the inhibition of bile acid enterohepatic
      circulation rather than increased endogenous bile acid synthesis. Moreover, serum
      bile acids are a good indicator of TAA-induced hepatotoxicity. 

PMID- 26222701
TI  - Critical limb ischemia: thrombogenic evaluation of two autologous cell therapy
      products and biologic profile in treated patients.
AB  - BACKGROUND: Cell therapy has been proposed as a salvage limb procedure in
      critical limb ischemia (CLI). Autologous cell therapy products (CTP) are obtained
      from patients with advanced peripheral arterial disease to be injected at the
      site of ischemia. Thrombogenicity of CTPs has not yet been assessed. The
      objectives were: 1) to assess thrombotic risk in candidates for cell therapy, 2)
      to evaluate two different CTPs in terms of thrombogenic potential, and 3) to
      evaluate clinical thrombotic events. STUDY DESIGN AND METHODS: In this ancillary
      study of a Phase I and II clinical trial, bone marrow (BM)-CTPs (n = 20) and CTPs
      obtained by cytapheresis (peripheral blood [PB]-CTPs; n = 20) were compared.
      Inflammatory and coagulation markers were measured at baseline and 24 hours after
      CTP implantation. CTP cell content and tissue factor (TF) expression (mRNA and
      protein) were analyzed. Thrombin generation assessed CTP-related thrombogenicity.
      RESULTS: All patients presented cardiovascular risk factors. At baseline, the
      patients' biologic profile was characterized by high levels of fibrinogen, C
      reactive protein (CRP), D-dimer, interleukin (IL)-6, and plasmatic TF, whereas IL
      10 was low. Although different in terms of cell composition, both BM- and PB-CTPs
      support low thrombin generation. Twenty-four hours after implantation, biologic
      markers remained stable in the PB-CTP group, except for IL-6. In the BM-CTP
      group, a significant increase of IL-6 but also of CRP and D-dimer was observed.
      Clinically, one single patient developed deep vein thrombosis 24 hours after the
      implantation of autologous PB-CTP. CONCLUSION: CTPs supported low thrombin
      generation and were well tolerated after calf implantation.

PMID- 26222702
TI  - Statistical Analysis of the Exchange Rate of Bitcoin.
AB  - Bitcoin, the first electronic payment system, is becoming a popular currency. We
      provide a statistical analysis of the log-returns of the exchange rate of Bitcoin
      versus the United States Dollar. Fifteen of the most popular parametric
      distributions in finance are fitted to the log-returns. The generalized
      hyperbolic distribution is shown to give the best fit. Predictions are given for
      future values of the exchange rate. 

PMID- 26222703
TI  - Correction: Native Wolbachia from Aedes albopictus Blocks Chikungunya Virus
      Infection In Cellulo.

PMID- 26222705
TI  - Correction: Novel ENU-Induced Mutation in Tbx6 Causes Dominant Spondylocostal
      Dysostosis-Like Vertebral Malformations in the Rat.

PMID- 26222704
TI  - The Michigan Model for Coronary Heart Disease in Type 2 Diabetes: Development and
      Validation.
AB  - OBJECTIVES: The aim of this study was to develop and validate a computer
      simulation model for coronary heart disease (CHD) in type 2 diabetes mellitus
      (T2DM) that reflects current medical and surgical treatments. RESEARCH DESIGN AND
      METHODS: We modified the structure of the CHD submodel in the Michigan Model for
      Diabetes to allow for revascularization procedures before and after first
      myocardial infarction, for repeat myocardial infarctions and repeat
      revascularization procedures, and for congestive heart failure. Transition
      probabilities that reflect the direct effects of medical and surgical therapies
      on outcomes were derived from the literature and calibrated to recently published
      population-based epidemiologic studies and randomized controlled clinical trials.
      Monte Carlo techniques were used to implement a discrete-state and discrete-time
      multistate microsimulation model. Performance of the model was assessed using
      internal and external validation. Simple regression analysis (simulated
      outcome=b(0)+b(1)*published outcome) was used to evaluate the validation results.
      RESULTS: For the 21 outcomes in the six studies used for internal validation,
      R(2) was 0.99, and the slope of the regression line was 0.98. For the 16 outcomes
      in the five studies used for external validation, R(2) was 0.81, and the slope
      was 0.84. CONCLUSIONS: Our new computer simulation model predicted the
      progression of CHD in patients with T2DM and will be incorporated into the
      Michigan Model for Diabetes to assess the cost-effectiveness of alternative
      strategies to prevent and treat T2DM.

PMID- 26222706
TI  - Synthesis of C8-N-Arylamine-Modified 2'-Deoxyguanosine-5'-Triphosphates and Their
      Effects on Primer Extension by DNA Polymerases.
AB  - C8-N-arylamine adducts of 2'-deoxyguanosine (2'-dG) play an important role in the
      induction of the chemical carcinogenesis caused by aromatic amines. C8-N-acetyl-N
      arylamine dG adducts that differ in their substitution pattern in the aniline
      moiety were converted by cycloSal technology into the corresponding C8-N-acetyl-N
      arylamine-2'-deoxyguanosine-5'-triphosphates and C8-NH-arylamine-2'
      deoxyguanosine-5'-triphosphates. Their conformation preference has been
      investigated by NOE spectroscopy and DFT calculations. The substrate properties
      of the C8-dG adducts were studied in primer-extension assays by using Klenow
      fragment exo(-) of Escherichia coli DNA polymerase I and human DNA polymerase
      beta. It was shown that the incorporation was independent of the substitution
      pattern in the aryl moiety and the N-acetyl group. Although the triphosphates
      were poor substrates for the human polymerases, they were incorporated twice
      before the termination of the elongation process occurred; this might demonstrate
      the importance of C8-N-arylamine-2'-deoxyguanosine-5'-triphosphates in chemical
      carcinogenesis. 

PMID- 26222707
TI  - Association of Psoriatic Disease With Uveitis: A Danish Nationwide Cohort Study.
AB  - IMPORTANCE: Psoriasis, psoriatic arthritis, and uveitis are inflammatory
      disorders with significant overlap in their inflammatory pathways. Limited
      evidence is available about the relationship between psoriatic disease and
      uveitis. OBJECTIVE: To investigate the potential bidirectional relationship
      between psoriatic disease, including psoriasis and psoriatic arthritis, and
      uveitis. DESIGN, SETTING, AND PARTICIPANTS: We performed a nationwide cohort
      study of the Danish population from January 1, 1997, through December 31, 2011.
      We included 74,129 Danish patients with psoriasis who were 18 years or older
      during the study period. Patients were identified through administrative
      registries, and information on age, sex, socioeconomic status, medication, and
      comorbidity was obtained using individual-level linkage of administrative
      registers. We performed data analysis from January 27 through March 4, 2015.
      EXPOSURES: Diagnosis of mild or severe psoriasis or psoriatic arthritis for
      uveitis risk and diagnosis of uveitis for the risk for psoriasis or psoriatic
      arthritis. MAIN OUTCOMES AND MEASURES: Diagnosis of uveitis, mild psoriasis,
      severe psoriasis, or psoriatic arthritis. We calculated incidence rates (IRs) and
      estimated IR ratios adjusted for potential confounders using Poisson regression.
      RESULTS: We identified 74,129 cases of psoriasis and psoriatic arthritis and
      13,114 cases of uveitis. The IRs (95% CIs) for uveitis were 2.02 (1.99-2.06),
      2.88 (2.33-3.56), 4.23 (2.40-7.45), and 5.49 (3.36-8.96) for the reference
      population and those with mild psoriasis, severe psoriasis, and psoriatic
      arthritis, respectively. In the reference population, these IRs (95% CIs) were
      9.37 (9.30-9.45), 1.12 (1.10-1.15), and 1.04 (1.01-1.06), and in patients with
      uveitis, these statistics were 15.51 (12.92-18.62), 2.66 (1.72-4.13), and 4.25
      (3.00-6.01) for mild psoriasis, severe psoriasis, and psoriatic arthritis,
      respectively. Adjusted IR ratios (95% CIs) for uveitis were 1.38 (1.11-1.70 [P =
      .02]), 1.40 (0.70-2.81 [P = .34]), and 2.50 (1.53-4.08 [P < .001]) for patients
      with mild psoriasis, severe psoriasis, and psoriatic arthritis, respectively. For
      patients with uveitis, IR ratios (95% CIs) were 1.59 (1.32-1.91 [P < .001]) for
      mild psoriasis, 2.17 (1.40-3.38 [P < .001]) for severe psoriasis, and 3.77 (2.66
      5.34 [P < .001]) for psoriatic arthritis, respectively. CONCLUSIONS AND
      RELEVANCE: We found a bidirectional association between psoriatic disease and
      uveitis. Increased focus on eye symptoms in patients with psoriasis and psoriatic
      arthritis and on skin and joint symptoms in patients with prior or current
      uveitis may be appropriate.

PMID- 26222708
TI  - Effects of Pravastatin on Human Placenta, Endothelium, and Women With Severe
      Preeclampsia.
AB  - Preeclampsia is a major pregnancy complication where excess placental release of
      soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin causes maternal
      endothelial and multisystem organ injury. Clinical trials have commenced
      examining whether pravastatin can be used to treat preeclampsia. However, the
      preclinical evidence supporting pravastatin as a treatment is limited to animal
      models, with almost no studies in human tissues. Therefore, we examined whether
      pravastatin reduced sFlt-1 and soluble endoglin secretion and decreased
      endothelial dysfunction in primary human tissues. Pravastatin reduced sFlt-1
      secretion from primary endothelial cells, purified cytotrophoblast cells, and
      placental explants obtained from women with preterm preeclampsia. It increased
      soluble endoglin secretion from endothelial cells but did not change secretion
      from placental explants. The regulation of sFlt-1 by pravastatin seemed to be
      mediated via the 3-hydroxy-3-methylglutaryl-coenzyme A reductase cholesterol
      synthesis pathway. Pravastatin also reduced markers of endothelial dysfunction,
      including vascular cell adhesion molecule-1 expression and leukocyte adhesion on
      endothelial cells and increased endothelial cell migration and invasion. We also
      treated 4 patients with preterm preeclampsia presenting at <30 weeks of gestation
      with daily pravastatin. Pravastatin seemed to stabilize blood pressure,
      proteinuria, and serum uric acid levels. Furthermore, serum sFlt-1 levels
      decreased. We collected the placentas at delivery and found that pravastatin
      reduced sFlt-1 secretion. These results indicate that pravastatin reduced sFlt-1
      and soluble endoglin production and decreased endothelial dysfunction in primary
      human tissues. We also present pilot data, suggesting that pravastatin can
      stabilize clinical and biochemical features of preterm preeclampsia. Our data
      obtained in human tissues support the concept that pravastatin is a candidate
      therapeutic for preeclampsia. CLINICAL TRIAL REGISTRATION: URL:
      http://www.anzctr.org.au. Unique identifier: ACTRN12613000268741.

PMID- 26222709
TI  - Adherence with antihypertensive drug therapy and the risk of heart failure in
      clinical practice.
AB  - Randomized clinical trials have shown that antihypertensive treatment reduces the
      risk of heart failure (HF). Limited evidence exists, however, on whether and to
      what extent this benefit is translated into real-life practice. A nested case
      control study was carried out by including the cohort of 76 017 patients from
      Lombardy (Italy), aged 40 to 80 years, who were newly treated with
      antihypertensive drugs during 2005. Cases were the 622 patients who experienced
      hospitalization for HF from initial prescription until 2012. Up to 5 controls
      were randomly selected for each case. Logistic regression was used to model the
      HF risk associated with adherence to antihypertensive drugs, which was measured
      by the proportion of days covered by treatment (PDC). Data were adjusted for
      several covariates. Sensitivity analyses were performed to account for possible
      sources of systematic uncertainty. Compared with patients with very low adherence
      (PDC, <=25%), low, intermediate, and high adherences were associated with
      progressively lower risk of HF, reduction in the high-adherence group (>75%)
      being 34% (95% confidence interval, 17%-48%). Similar effects were observed in
      younger (40-70 years) and older (71-80 years) patients and between patients
      treated with angiotensin-converting enzyme inhibitors, angiotensin receptor
      blockers, and diuretics. There was no evidence that adherence with calcium
      channel blockers reduced the HF risk. Antihypertensive treatment lowers the HF
      risk in real-life practice, but adherence to treatment is necessary for a
      substantial benefit to take place. This is the case with a variety of
      antihypertensive drugs. 

PMID- 26222710
TI  - Hypoglycemic effects of Zanthoxylum alkylamides by enhancing glucose metabolism
      and ameliorating pancreatic dysfunction in streptozotocin-induced diabetic rats.
AB  - This study aimed to evaluate the hypoglycemic effect of Zanthoxylum alkylamides
      and explore the potential mechanism in streptozotocin (STZ)-induced diabetic
      rats. Diabetic rats were orally treated with 3, 6, and 9 mg per kg bw alkylamides
      daily for 28 days. As the alkylamide dose increased, the relative weights of the
      liver and kidney, fasting blood glucose, and fructosamine levels were
      significantly decreased. The alkylamides also significantly increased the body
      weight and improved the oral glucose tolerance of the rats. Likewise, the
      alkylamides significantly increased the levels of liver and muscle glycogen and
      plasma insulin. These substances further alleviated the histopathological changes
      in the pancreas of the diabetic rats. The beneficial effects of high-dose
      alkylamides showed a comparable activity to the anti-diabetic drug glibenclamide.
      Western blot and real-time PCR results revealed that the alkylamide treatment
      significantly decreased the expression levels of the key enzymes
      (phosphoenolpyruvate caboxykinase and glucose-6-phosphatase) involved in
      gluconeogenesis and increased the glycolysis enzyme (glucokinase) in the liver,
      and enhanced the expression levels of pancreatic duodenal homeobox-1,
      glucokinase, and glucose transporter 2 in the pancreas. In addition, it was also
      observed that the alkylamides, unlike glibenclamide, increased the transient
      receptor potential cation channel subfamily V member 1 and decreased cannabinoid
      receptor 1 expressions in the liver and pancreas. Therefore, alkylamides can
      prevent STZ-induced hyperglycemia by altering the expression levels of the genes
      related to glucose metabolism and by ameliorating pancreatic dysfunction. 

PMID- 26222711
TI  - Study of high quality spinel zinc gallate nanowires grown using CVD and ALD
      techniques.
AB  - High quality single crystalline zinc gallate (ZnGa2O4) nanowires (NWs) were grown
      using a combination of chemical vapor deposition and atomic layer deposition
      techniques. Morphological, structural and optical investigations revealed the
      formation of Ga2O3-ZnO core-shell NWs and their conversion into ZnGa2O4 NWs after
      annealing via a solid state reaction. This material conversion was systematically
      confirmed for single NWs by various measurement techniques including scanning and
      transmission electron microscopy, Raman spectroscopy and voltage-dependent
      cathodoluminescence. Moreover, a model system based on the obtained results has
      been provided explaining the formation mechanism of the ZnGa2O4 NWs. 

PMID- 26222712
TI  - OROS-Methylphenidate-Induced Raynaud's Phenomenon: A Dose-Related Side Effect.

PMID- 26222713
TI  - Invariom based electron density studies on the C/Si analogues haloperidol/sila
      haloperidol and venlafaxine/sila-venlafaxine.
AB  - The subjects of this study are the structures and electron densities of the
      carbon/silicon analogues haloperidol/sila-haloperidol (1a/1b) and
      venlafaxine/sila-venlafaxine (2a/2b). The parent carbon compounds 1a (an
      antipsychotic agent) and 2a (an antidepressant) are both in clinical use. For
      haloperidol/sila-haloperidol, three published structures were studied in more
      detail: the structures of haloperidol hydrochloride (1a.HCl), haloperidol
      hydropicrate (1a.HPic) and sila-haloperidol hydrochloride (1b.HCl). For
      venlafaxine/sila-venlafaxine, the published structures of venlafaxine (2a),
      venlafaxine hydrochloride (2a.HCl; as orthorhombic (2a.HCl-ortho) and monoclinic
      polymorph (2a.HCl-mono)) and sila-venlafaxine hydrochloride (2b.HCl) were
      investigated. Based on these structures, the molecular electron densities were
      reconstructed by using the invariom formalism. They were further analysed in
      terms of Bader's quantum theory of atoms in molecules, electrostatic potentials
      mapped onto electron density isosurfaces and Hirshfeld surfaces. These studies
      were performed with a special emphasis on the comparison of the corresponding
      carbon/silicon analogues. 

PMID- 26222714
TI  - idDock+: Integrating Machine Learning in Probabilistic Search for Protein-Protein
      Docking.
AB  - Predicting the three-dimensional native structures of protein dimers, a problem
      known as protein-protein docking, is key to understanding molecular interactions.
      Docking is a computationally challenging problem due to the diversity of
      interactions and the high dimensionality of the configuration space. Existing
      methods draw configurations systematically or at random from the configuration
      space. The inaccuracy of scoring functions used to evaluate drawn configurations
      presents additional challenges. Evidence is growing that optimization of a
      scoring function is an effective technique only once the drawn configuration is
      sufficiently similar to the native structure. Therefore, in this article we
      present a method that employs optimization of a sophisticated energy function,
      FoldX, only to locally improve a promising configuration. The main question of
      how promising configurations are identified is addressed through a machine
      learning method trained a priori on an extensive dataset of functionally diverse
      protein dimers. To deal with the vast configuration space, a probabilistic search
      algorithm operates on top of the learner, feeding to it configurations drawn at
      random. We refer to our method as idDock+, for informatics-driven Docking.
      idDock+is tested on 15 dimers of different sizes and functional classes. Analysis
      shows that on all systems idDock+finds a near-native structure and is comparable
      in accuracy to other state-of-the-art methods. idDock+ represents one of the
      first highly efficient hybrid methods that combines fast machine learning models
      with demanding optimization of sophisticated energy scoring functions. Our
      results indicate that this is a promising direction to improve both efficiency
      and accuracy in docking. 

PMID- 26222725
TI  - Safety, Feasibility, and Hemodynamic Effects of Mild Hypothermia in Transcatheter
      Aortic Valve Replacement: The TAVR-CHILL Trial.
AB  - The safety, feasibility, and hemodynamic effects of mild hypothermia (MH) induced
      by transnasal cooling were studied in transcatheter aortic valve replacement
      (TAVR). MH is a common therapy following cardiac arrest and seems to have
      favorable effects in myocardial infarction and on hemodynamic stability. In TAVR,
      hemodynamic instability is common during rapid pacing. Twenty subjects undergoing
      TAVR were randomized 1:1 to hypothermia or normothermia. Hemodynamic endpoints
      were mean arterial blood pressure and required dosage of vasoactive and inotropic
      drugs. Patients were followed up at 6 months. All patients in the MH group (n=10)
      reached the target temperature of 34 degrees C before first rapid pacing.
      Tympanic and urinary bladder temperature remained significantly lower in the MH
      group during the procedure. No adverse effects of cooling were observed. Mean
      arterial pressure was higher in the MH group (90+/-20 mm Hg) than in the control
      group (71+/-13 mm Hg) at the start of the procedure, at first rapid pacing (94+/
      19 vs. 80+/-16 mm Hg), and at balloon aortic valvuloplasty (90+/-17 vs. 73+/-14
      mm Hg). Less norepinephrine was administered to the hypothermia group. Transnasal
      cooling during TAVR was safe and well tolerated. We observed a more stable
      hemodynamic profile in the MH group, indicated by higher blood pressure and lower
      levels of vasoactive drugs required. A larger study of patients with severe
      ventricular dysfunction is required to more comprehensively investigate the
      hemodynamic effects of transnasal cooling in TAVR.

PMID- 26222724
TI  - FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and
      Vascular Injury in Rats with Diabetic Retinopathy.
AB  - Diabetic retinopathy features inflammation as well as injury to glial cells and
      the microvasculature, which are influenced by hypertension and overactivity of
      the renin-angiotensin system. FT011 is an anti-inflammatory and anti-fibrotic
      agent that has been reported to attenuate organ damage in diabetic rats with
      cardiomyopathy and nephropathy. However, the potential therapeutic utility of
      FT011 for diabetic retinopathy has not been evaluated. We hypothesized that FT011
      would attenuate retinopathy in diabetic Ren-2 rats, which exhibit hypertension
      due to an overactive extra-renal renin-angiotensin system. Diabetic rats were
      studied for 8 and 32 weeks and received intravitreal injections of FT011 (50 MUM)
      or vehicle (0.9% NaCl). Comparisons were to age-matched controls. In the 8-week
      study, retinal inflammation was examined by quantitating vascular leukocyte
      adherence, microglial/macrophage density and the expression of inflammatory
      mediators. Macroglial Muller cells, which exhibit a pro-inflammatory and pro
      angiogenic phenotype in diabetes, were evaluated in the 8-week study as well as
      in culture following exposure to hyperglycaemia and FT011 (10, 30, 100 MUM) for
      72 hours. In the 32-week study, severe retinal vasculopathy was examined by
      quantitating acellular capillaries and extracellular matrix proteins. In diabetic
      rats, FT011 reduced retinal leukostasis, microglial density and mRNA levels of
      intercellular adhesion molecule-1 (ICAM-1). In Muller cells, FT011 reduced
      diabetes-induced gliosis and vascular endothelial growth factor (VEGF)
      immunolabeling and the hyperglycaemic-induced increase in ICAM-1, monocyte
      chemoattractant protein-1, CCL20, cytokine-induced neutrophil chemoattractant-1,
      VEGF and IL-6. Late intervention with FT011 reduced acellular capillaries and the
      elevated mRNA levels of collagen IV and fibronectin in diabetic rats. In
      conclusion, the protective effects of FT011 in cardiorenal disease extend to key
      elements of diabetic retinopathy and highlight its potential as a treatment
      approach. 

PMID- 26222727
TI  - 8% phenol solution for the treatment of Epidermal Growth Factor Receptor
      inhibitor-induced periungual pyogenic granulomas.

PMID- 26222726
TI  - Epstein-Barr Virus-Positive Diffuse Large B-Cell Lymphoma in the Elderly: A
      Matched Case-Control Analysis.
AB  - BACKGROUND: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma
      (DLBCL) in the elderly has rarely been reported. This study aimed to explore the
      clinical characteristics and prognosis of this entity. METHODS: In situ
      hybridization (ISH) analysis of Epstein-Barr virus (EBV) and immunohistochemistry
      was performed in 230 tumor specimens from consecutive de novo DLBCL patients over
      50 years old. A matched-case control analysis (1:3) was utilized to compare EBV
      positive and EBV-negative DLBCL in the elderly. RESULTS: A total of 16 patients
      (7.0%) were diagnosed with EBV-positive DLBCL. Of these 16 cases, the median age
      was 62 years, with a male to female ratio of 11:5. Elderly EBV-positive DLBCL
      patients had a higher incidence of non-germinal center B-cell (non-GCB) subtypes
      (87.5%) and high Ki67 (75%) and CD30 expression (93.8%). For EBV-positive
      patients undergoing initial chemotherapy, 7 of 16 (43.8%) had complete remission,
      2 (12.5%) had partial remission, 2 (12.5%) had stable disease, and 5 (31.3%) had
      progressive disease. The median overall survival was 9 months for the EBV
      positive patients. A matched-case control analysis suggested that EBV-positive
      patients had inferior survival outcomes compared with EBV-negative patients (3
      year progression-free survival [PFS]: 25% vs. 76.7%, respectively; 3-year overall
      survival [OS]: 25% vs. 77.4%, respectively; P<0.001). CONCLUSION: EBV-positive
      DLBCL of the elderly is associated with an inferior clinical course and inferior
      survival outcomes. The role of EBV in this disease and the optimal management of
      this subgroup warrants further investigation.

PMID- 26222728
TI  - The purse-string suture: our experience in our 4 best case reports.

PMID- 26222729
TI  - Merkel cell carcinoma arising on a pre-existing Bowen's disease: is it just by
      chance?
AB  - Merkel cell carcinoma (MCC) is a cutaneous carcinoma with neuroendocrine
      differentiation. It arises typically on sun-exposed areas of elderly men as an
      asymptomatic, rapidly growing, red nodule. Although it is usually found as a
      solitary nodule, in almost one third of cases MCC may be associated with other
      malignancies such as basal cell or squamous cell carcinomas. Merkel cell
      carcinoma should be considered as differential diagnosis every time we have a
      rapidly growing, red nodule, arising in an elderly patient with signs of sun
      damage. We report a case of MCC developing in association with a pre-existing
      Bowen's disease. The association between MCC and Bowen's disease is quite common
      and their area of occurrence is usually a sun-exposed area. Ultraviolet radiation
      contributes to the etiology of both the malignancies.

PMID- 26222731
TI  - On Valence-Band Splitting in Layered MoS2.
AB  - As a representative two-dimensional semiconducting transition-metal
      dichalcogenide (TMD), the electronic structure in layered MoS2 is a collective
      result of quantum confinement, interlayer interaction, and crystal symmetry. A
      prominent energy splitting in the valence band gives rise to many intriguing
      electronic, optical, and magnetic phenomena. Despite numerous studies, an
      experimental determination of valence-band splitting in few-layer MoS2 is still
      lacking. Here, we show how the valence-band maximum (VBM) splits for one to five
      layers of MoS2. Interlayer coupling is found to contribute significantly to
      phonon energy but weakly to VBM splitting in bilayers, due to a small interlayer
      hopping energy for holes. Hence, spin-orbit coupling is still predominant in the
      splitting. A temperature-independent VBM splitting, known for single-layer MoS2,
      is, thus, observed for bilayers. However, a Bose-Einstein type of temperature
      dependence of VBM splitting prevails in three to five layers of MoS2. In such few
      layer MoS2, interlayer coupling is enhanced with a reduced interlayer distance,
      but thermal expansion upon temperature increase tends to decouple adjacent layers
      and therefore decreases the splitting energy. Our findings that shed light on the
      distinctive behaviors about VBM splitting in layered MoS2 may apply to other
      hexagonal TMDs as well. They will also be helpful in extending our understanding
      of the TMD electronic structure for potential applications in electronics and
      optoelectronics. 

PMID- 26222733
TI  - A role for chromatin topology in imprinted domain regulation.
AB  - Recently, many advancements in genome-wide chromatin topology and nuclear
      architecture have unveiled the complex and hidden world of the nucleus, where
      chromatin is organized into discrete neighbourhoods with coordinated gene
      expression. This includes the active and inactive X chromosomes. Using X
      chromosome inactivation as a working model, we utilized publicly available
      datasets together with a literature review to gain insight into topologically
      associated domains, lamin-associated domains, nucleolar-associating domains,
      scaffold/matrix attachment regions, and nucleoporin-associated chromatin and
      their role in regulating monoallelic expression. Furthermore, we comprehensively
      review for the first time the role of chromatin topology and nuclear architecture
      in the regulation of genomic imprinting. We propose that chromatin topology and
      nuclear architecture are important regulatory mechanisms for directing gene
      expression within imprinted domains. Furthermore, we predict that dynamic changes
      in chromatin topology and nuclear architecture play roles in tissue-specific
      imprint domain regulation during early development and differentiation. 

PMID- 26222734
TI  - Enhancing Tissue Engineering and Regenerative Medicine Product Commercialization:
      The Role of Science in Regulatory Decision-Making for the TE/RM Product
      Development.
AB  - TERMIS-AM Industry Committee (TERMIS-AM/IC), in collaboration with the TERMIS
      Europe (EU)/IC, conducted a symposium involving the European Medicines Agency and
      the U.S. Food and Drug Administration (FDA) toward building an understanding of
      the rational basis for regulatory decision-making and providing a framework for
      decisions made during the evaluation of safety and efficacy of TE/RM
      technologies. This symposium was held in August 2012 during the TERMIS-WC in
      Vienna, Austria. Emerging from this international initiative by the European
      Union and the United States, representatives from the respective agencies
      demonstrated that there are ongoing interagency efforts for developing common
      national practices toward harmonization of regulatory requirements for the TE/RM
      products. To extend a broad-based understanding of the role of science in
      regulatory decision-making, TERMIS-AM/IC, in cooperation with the FDA, organized
      a symposium at the 2014 TERMIS-AM Annual Meeting, which was held in Washington,
      DC. This event provided insights from leaders in the FDA and TERMIS on the
      current status of regulatory approaches for the approved TE/RM products, the use
      of science in making regulatory decisions, and TE/RM technologies that are in the
      development pipeline to address unmet medical needs. A far-ranging discussion
      with FDA representatives, industrialists, physicians, regenerative medicine
      biologists, and tissue engineers considered the gaps in today's scientific and
      regulatory understanding of TE/RM technologies. The identified gaps represent
      significant opportunities to advance TE/RM technologies toward commercialization.

PMID- 26222735
TI  - Local bone quality affects the outcome of prosthetic total knee arthroplasty.
AB  - Osteoporosis and osteoarthritis commonly coexist in the elderly. In patients
      undergoing prosthetic total knee arthroplasty (TKA), the bone quality around the
      knee joint may affect the safety of prosthetic implantation and consequently
      satisfaction with the surgical outcome. We recruited 50 postmenopausal women
      undergoing TKA for primary osteoarthritis; 43 completed the study protocol. The
      bone quality parameters of the operated knee, including bone mineral density
      assessed using dual-energy X-ray absorptiometry and microarchitecture variables
      assessed using micro-computed tomography, were determined. Surgical outcomes were
      assessed according to immediate (<1 week) postoperative pain quantified using the
      visual analog scale and knee function quantified using the Knee Injury and
      Osteoarthritis Outcome Score (KOOS) at 2 and 6 months postoperatively. The
      influence of bone quality parameters on surgical outcomes was analyzed using
      simple and multiple regression analyses. Volumetric bone mineral density (R(2)  =
      0.187-0.234, p < 0.01), the structural model index (R(2)  = 0.103-0.181, p <
      0.05), and trabecular separation (R(2)  = 0.289-0.424, p < 0.05) were
      significantly associated with postoperative pain and improvement according to the
      KOOS. In conclusion, local bone quality, including mineral content and
      microarchitecture, affects the surgical outcome of TKA.

PMID- 26222736
TI  - Trajectory of platelets in pregnancy - do low-risk women need an intrapartum full
      blood count prior to epidural?
AB  - This study aimed to investigate whether pregnant women with a normal 28-week
      gestation platelet count and no high-risk conditions for thrombocytopenia require
      a pre-epidural platelet count. All 1844 included women (platelet count > 150 *
      10(9) /L at 28 weeks' gestation, term singleton birth, no thrombocytopenia risk
      conditions) had a platelet count > 100 * 10(9) /L prebirth, suggesting low-risk
      pregnant women do not require pre-epidural full blood count solely to check
      platelet count.

PMID- 26222738
TI  - Preventability of Hospital-Acquired Venous Thromboembolism.

PMID- 26222739
TI  - SrCo(0.9)Ti(0.1)O(3-delta) As a New Electrocatalyst for the Oxygen Evolution
      Reaction in Alkaline Electrolyte with Stable Performance.
AB  - The development of efficient, inexpensive, and stable electrocatalysts for the
      oxygen evolution reaction (OER) is critical for many electrochemical energy
      conversion technologies. The prohibitive price and insufficient stability of the
      state-of-the-art IrO2 electrocatalyst for the OER inhibits its use in practical
      devices. Here, SrM0.9Ti0.1O3-delta (M = Co, Fe) perovskites with different B-site
      transition metal elements were investigated as potentially cheaper OER
      electrocatalysts. They were prepared through a typical sol-gel route, and their
      catalytic activities for the OER in alkaline medium were comparatively studied
      using rotating disk electrodes. Both materials show high initial intrinsic
      activities in alkaline electrolyte for the OER, comparable to the benchmark
      perovskite-type electrocatalyst Ba0.5Sr0.5Co0.8Fe0.2O3-delta (BSCF), but
      SrCo0.9Ti0.1O3-delta (SCT) possessed more operational stability than
      SrFe0.9Ti0.1O3-delta (SFT), even better than BSCF and IrO2 catalysts. Based on
      the X-ray photoelectron spectra analysis of the oxidation states of the surface
      Co/Fe in both SFT and SCT before and after the OER tests, an explanation for
      their different operational stabilities was proposed by adopting a reported
      activity descriptor correlated to the eg occupancy of the 3d electron of the
      surface transition metal cations in the perovskite oxides. The above results
      indicate that SCT is a promising alternative electrocatalyst for the OER and can
      be used in electrochemical devices for water oxidation. 

PMID- 26222741
TI  - Time-Dependent Investigation of Surface Nanostructures of Weak-Phase-Separated
      Block Copolymer Films.
AB  - An analysis of the morphological behavior of substrate-supported diblock
      copolymer [polystyrene-block-poly(tert-butyl acrylate) (PS-b-PtBA)] films was
      carried out with the help of selective hydrolysis. The hydrolysis was a pseudo
      first-order rate reaction as proven by infrared (IR) spectra. With the
      hydrolysis, the water-swelled poly(acrylic acid) (PAA) phase was obtained on the
      PtBA phase, and the surface morphology transformation was investigated by tapping
      mode atomic force microscopy (TMAFM). Together with the equilibrium swelling
      experiments, the morphology changes with hydrolysis were recorded in situ and
      time-dependent variation of the phase separation was successfully detected. The
      study made it possible to detect in situ the reorientation of functional groups
      in phase-separated films, which may find broad applications in the field of
      nanosensing. 

PMID- 26222740
TI  - Identification of Spinal Cord MicroRNA and Gene Signatures in a Model of Chronic
      Stress-Induced Visceral Hyperalgesia in Rat.
AB  - INTRODUCTION: Animal studies have shown that stress could induce epigenetic and
      transcriptomic alterations essential in determining the balance between adaptive
      or maladaptive responses to stress. We tested the hypothesis that chronic stress
      in rats deregulates coding and non-coding gene expression in the spinal cord,
      which may underline neuroinflammation and nociceptive changes previously observed
      in this model. METHODS: Male Wistar rats were exposed to daily stress or handled,
      for 10 days. At day 11, lumbar spinal segments were collected and processed for
      mRNA/miRNA isolation followed by expression profiling using Agilent SurePrint Rat
      Exon and Rat miRNA Microarray platforms. Differentially expressed gene lists were
      generated using the dChip program. Microarrays were analyzed using the Ingenuity
      Pathways Analysis (IPA) tool from Ingenuity Systems. Multiple methods were used
      for the analysis of miRNA-mRNA functional modules. Quantitative real time RT-PCR
      for Interleukin 6 signal transducer (gp130), the Signal Transducer And Activator
      Of Transcription 3 (STAT3), glial fibrillary acidic protein and mir-17-5p were
      performed to confirm levels of expression. RESULTS: Gene network analysis
      revealed that stress deregulated different inflammatory (IL-6, JAK/STAT, TNF) and
      metabolic (PI3K/AKT) signaling pathways. MicroRNA array analysis revealed a
      signature of 39 deregulated microRNAs in stressed rats. MicroRNA-gene network
      analysis showed that microRNAs are regulators of two gene networks relevant to
      inflammatory processes. Specifically, our analysis of miRNA-mRNA functional
      modules identified miR-17-5p as an important regulator in our model. We verified
      miR-17-5p increased expression in stress using qPCR and in situ hybridization. In
      addition, we observed changes in the expression of gp130 and STAT3 (involved in
      intracellular signaling cascades in response to gp130 activation), both predicted
      targets for miR-17-5p. A modulatory role of spinal mir17-5p in the modulation of
      visceral sensitivity was confirmed in vivo. CONCLUSION: Using an integrative high
      throughput approach, our findings suggest a link between miR-17-5p increased
      expression and gp130/STAT3 activation providing new insight into the possible
      mechanisms mediating the effect of chronic stress on neuroinflammation in the
      spinal cord.

PMID- 26222743
TI  - Co-endemicity of Plasmodium falciparum and Intestinal Helminths Infection in
      School Age Children in Rural Communities of Kwara State Nigeria.
AB  - BACKGROUND: Malaria and intestinal helminths co-infection are major public health
      problems particularly among school age children in Nigeria. However the magnitude
      and possible interactions of these infections remain poorly understood. This
      study determined the prevalence, impact and possible interaction of Plasmodium
      falciparum and intestinal helminths co-infection among school children in rural
      communities of Kwara State, Nigeria. METHODS: Blood, urine and stool samples were
      collected from 1017 primary school pupils of ages 4-15 years. Stool samples were
      processed using both Kato-Katz and formol-ether concentration techniques and
      microscopically examined for intestinal helminths infection. Urine samples were
      analyzed using sedimentation method for Schistosoma haematobium. Plasmodium
      falciparum was confirmed by microscopy using thick and thin blood films methods
      and packed cell volume (PCV) was determined using hematocrit reader. Univariate
      analysis and chi-square statistical tests were used to analyze the data. RESULTS:
      Overall, 61.2% of all school children had at least an infection of either P.
      falciparum, S. haematobium, or intestinal helminth. S. haematobium accounted for
      the largest proportion (44.4%) of a single infection followed by P. falciparum
      (20.6%). The prevalence of malaria and helminth co-infection in the study was
      14.4%. Four species of intestinal helminths were recovered from the stool samples
      and these were hookworm (22.5%), Hymenolepis species (9.8%), Schistosoma mansoni
      (2.9%) and Enterobius vermicularis (0.6%). The mean densities of P. falciparum in
      children co-infected with S. haematobium and hookworm were higher compared to
      those infected with P. falciparum only though not statistically significant (p =
      0.062). The age distribution of both S. haematobium (p = 0.049) and hookworm (p =
      0.034) infected children were statistically significant with the older age group
      (10-15 years) recording the highest prevalence of 47.2% and 25% respectively.
      Children who were infected with S. haematobium (RR = 1.3) and hookworm (RR = 1.4)
      have equal chances of being infected with P. falciparum as children with no worm
      infection. On the other hand children infected with Hymenolepis spp. (p<0.0001)
      are more likely to be infected with P. falciparum than Hymenolepis spp.
      uninfected children (RR = 2.0). CONCLUSIONS: These findings suggest that multiple
      parasitic infections are common in school age children in rural communities of
      Kwara State Nigeria. The Hymenolepis spp. induced increase susceptibility to P.
      falciparum could have important consequences on how concurrent infections affect
      the expression or pathogenesis of these infections.

PMID- 26222744
TI  - Serum and tissue pharmacokinetics of silibinin after per os and i.v.
      administration to mice as a HP-beta-CD lyophilized product.
AB  - Silibinin, the main active component of Silybum marianum is a hepatoprotective
      and antioxidant agent with antitumor effect, exhibiting very low aqueous
      solubility and oral bioavailability limiting its use in therapeutics. We
      characterized serum and tissue pharmacokinetics of SLB, calculated its absolute
      bioavailability and developed an open loop physiologically based pharmacokinetic
      (PBPK) model, after oral (per os, p.o) and intravenous (i.v.) administration in
      mice as water-soluble silibinin-hydroxypropyl-beta-cyclodextrin (SLB-HP-beta-CD)
      lyophilized product. 60 C57Bl/6J mice were divided into groups of 5, each group
      representing one sampling time point. SLB-HP-beta-CD lyophilized product was
      administered orally (50mg/kg) and i.v. (20mg/kg) after reconstitution with water
      for injection. Blood and tissue samples were collected at selected time points
      after animal sacrificed, properly treated and analyzed with HPLC-PDA for non
      metabolized and total SLB. NONMEM pharmacokinetic analysis revealed a 2
      compartment PK model to describe serum SLB pharmacokinetics, with zero order
      absorption after oral administration and was applied as forcing function to an
      open loop PBPK model incorporating heart, liver, kidneys and lungs. Tissue/plasma
      Kp values were estimated using i.v. data and can be used to predict tissue SLB
      distribution after oral administration. Absolute oral bioavailability of SLB from
      the lyophilized SLB-HP-beta-CD product was 10 times higher than after
      administration of pure SLB. 

PMID- 26222742
TI  - Nucleosome functions in spindle assembly and nuclear envelope formation.
AB  - Chromosomes are not only carriers of the genetic material, but also actively
      regulate the assembly of complex intracellular architectures. During mitosis,
      chromosome-induced microtubule polymerisation ensures spindle assembly in cells
      without centrosomes and plays a supportive role in centrosome-containing cells.
      Chromosomal signals also mediate post-mitotic nuclear envelope (NE) re-formation.
      Recent studies using novel approaches to manipulate histones in oocytes, where
      functions can be analysed in the absence of transcription, have established that
      nucleosomes, but not DNA alone, mediate the chromosomal regulation of spindle
      assembly and NE formation. Both processes require the generation of RanGTP by
      RCC1 recruited to nucleosomes but nucleosomes also acquire cell cycle stage
      specific regulators, Aurora B in mitosis and ELYS, the initiator of nuclear pore
      complex assembly, at mitotic exit. Here, we review the mechanisms by which
      nucleosomes control assembly and functions of the spindle and the NE, and discuss
      their implications for genome maintenance. 

PMID- 26222745
TI  - Polymeric nanoparticles modified with fatty acids encapsulating betamethasone for
      anti-inflammatory treatment.
AB  - Topical glucocorticosteroids were incorporated into nanocarrier-based
      formulations, to overcome side effects of conventional formulations and to
      achieve maximum skin deposition. Nanoparticulate carriers have the potential to
      prolong the anti-inflammatory effect and provide higher local concentration of
      drugs, offering a better solution for treating dermatological conditions and
      improving patient compliance. Nanoparticles were formulated with poly-epsilon
      caprolactone as the polymeric core along with stearic acid as the fatty acid, for
      incorporation of betamethasone-21-acetate. Oleic acid was applied as the coating
      fatty acid. Improvement of the drug efficacy, and reduction in drug degradation
      with time in the encapsulated form was examined, while administering it locally
      through controlled release. Nanoparticles were spherical with mean size of 300 nm
      and negatively charged surface. Encapsulation efficiency was 90%. Physicochemical
      stability in aqueous media of the empty and loaded nanoparticles was evaluated
      for six months. Drug degradation was reduced compared to free drug, after
      encapsulation into nanoparticles, avoiding the potency decline and promoting a
      controlled drug release over one month. Fourier transform infrared spectroscopy
      and thermal analysis confirmed drug entrapment, while cytotoxicity studies
      performed in vitro on human keratinocytes, Saccharomyces cerevisiae models and
      Artemia salina, showed a dose-response relationship for nanoparticles and free
      drug. In all models, drug loaded nanoparticles had a greater inhibitory effect.
      Nanoparticles increased drug permeation into lipid membranes in vitro.
      Preliminary safety and permeation studies conducted on rats, showed betamethasone
      21-acetate in serum after 48 h application of a gel containing nanoparticles. No
      skin reactions were observed. In conclusion, the developed nanoparticles may be
      applied as topical treatment, after encapsulation of betamethasone-21-acetate, as
      nanoparticles promote prolonged drug release, increase drug stability in aqueous
      media, reducing drug degradation, and increase drug permeability through lipid
      membranes.

PMID- 26222746
TI  - Treatment of Cases of Neisseria gonorrhoeae and Chlamydia trachomatis in
      Emergency Department Patients.
AB  - BACKGROUND: The aim of this study was to determine the proportion of patients
      treated appropriately, both presumptively in the emergency department (ED), and
      at follow-up, among those patients who ultimately tested positive for either
      Neisseria gonorrhoeae (NG) or Chlamydia trachomatis (CT). Secondary aims were to
      characterize patients who received appropriate presumptive antibiotic treatment
      of both NG and CT at the time of ED visit and to compare them to patients who did
      not receive appropriate presumptive therapy. METHODS: A retrospective chart
      review was performed on 500 patients randomly chosen from those that had positive
      NG or CT test results performed in the ED between January 10 and June 11. The
      Center for Disease Control and Prevention 2010 STD Treatment Guidelines were used
      to determine appropriate antibiotics. RESULTS: We found 54% (95% confidence
      interval [CI], 49%-58%) of patients received appropriate antibiotics at ED visit
      and an additional 31% (95% CI, 27%-35%) were treated at our medical center on
      follow-up. Fifteen percent did not have documented treatment. Providers
      presumptively treated 46% (95% CI, 42%-50%) of patients studied with antibiotics
      appropriate for both NG and CT. The presence of behavioral risk factors and, for
      males, the presence of genital symptoms were the only factors independently
      associated with presumptive ED treatment. CONCLUSIONS: Among patients diagnosed
      as having NG or CT in this ED, a portion were not documented to ever receive
      appropriate antibiotics, although a call-back system is in place. Presumptive
      treatment was not commonly used in this ED but may be necessary given the high
      number of patients who never got treated.

PMID- 26222748
TI  - Contextual Factors Surrounding Anal Intercourse in Women: Implications for
      Sexually Transmitted Infection/HIV Prevention.
AB  - BACKGROUND: Our objectives were to describe women's reasons for engaging in anal
      intercourse (AI), contextual factors surrounding AI, and how these vary by
      current rectal sexually transmitted infection (STI) status, and to assess women's
      knowledge and concerns about rectal infections. METHODS: Between January 2011 and
      June 2013, we conducted semistructured, qualitative interviews among 40 women
      attending public sexually transmitted disease clinics in Los Angeles County,
      California. Women were eligible if they were at least 18 years of age, reported
      AI in the past 90 days, and were tested for rectal Chlamydia trachomatis and
      Neisseria gonorrhoeae. Interviews, which were guided by the theory of gender and
      power, were transcribed and coded to explore contextual factors surrounding AI.
      RESULTS: On average, participants reported having 3 AI partners in their lifetime
      and most (n = 30) reported being in a serious relationship with a main/regular
      sex partner at the time of the interview. Motivations for engaging in AI and
      feelings about AI varied by rectal STI status. Women with a rectal STI more
      prominently conveyed the idea that AI was intended to please their sexual
      partner, whereas those who did not have a rectal STI reported AI more as a way to
      increase intimacy and personal sexual gratification. Almost all women (regardless
      of rectal STI status) reported limited to no knowledge about the risk of rectal
      STIs. CONCLUSIONS: Among women, risk of acquiring rectal STIs may vary by reason
      for engaging in unprotected AI as well as other contextual factors. Providers
      should consider addressing these contextual factors to reduce risk.

PMID- 26222747
TI  - Hydrogen Peroxide-Producing Lactobacilli Are Associated With Lower Levels of
      Vaginal Interleukin-1beta, Independent of Bacterial Vaginosis.
AB  - BACKGROUND: The presence of hydrogen peroxide (H2O2)-producing lactobacilli in
      the vagina is associated with decreased rates of preterm birth and HIV
      acquisition. We hypothesize that this is due to immunomodulatory effects of these
      species. METHODS: Concentrations of interleukin (IL)-1beta, IL-6, IL-8, secretory
      leukocyte protease inhibitor, and human beta-defensin 2 were quantified from
      vaginal swabs from 4 groups of women: women with and without bacterial vaginosis
      (BV) by Nugent score, further stratified by detection of H2O2-producing
      lactobacilli by semiquantitative culture. Ten quantitative polymerase chain
      reaction assays characterized the presence and quantity of select Lactobacillus
      and BV-associated species in each group. Levels of immune markers and bacteria
      were compared between the 4 groups using analysis of variance, Kruskal-Wallis,
      Mann-Whitney U, or chi tests. RESULTS: Swabs from 110 women from 4 groups were
      included: 26 had a normal Nugent score (BV-), and no H2O2-producing lactobacilli
      detected (H2O2-); 47 were BV-, H2O2+; 27 BV+, H2O2-; and 10 BV+, H2O2+. The
      groups were similar in age, marital status, and reproductive history, but not
      ethnicity: the BV-, H2O2- group had more white participants (P = 0.02). In women
      with and without BV, IL-1beta was lower in the H2O2+ groups. Human beta-defensin
      2 was lowest in BV+ H2O2- women and highest in BV-, H2O2-. Secretory leukocyte
      protease inhibitor was lower in women with BV and did not differ by the presence
      of H2O2-producing lactobacilli. In regression analysis, higher quantities of
      Lactobacillus crispatus were associated with lower quantities of IL-1beta.
      Detection and quantity of BV-associated species by quantitative polymerase chain
      reaction was significantly different between women with and without BV, but not
      between women with and without H2O2-producing lactobacilli within those groups.
      CONCLUSIONS: The presence of H2O2-producing lactobacilli is associated with lower
      levels of some vaginal proinflammatory cytokines, even in women with BV.

PMID- 26222749
TI  - Estimating the Public Health Burden Associated With Adverse Pregnancy Outcomes
      Resulting From Syphilis Infection Across 43 Countries in Sub-Saharan Africa.
AB  - BACKGROUND: Untreated syphilis in pregnancy is associated with adverse clinical
      outcomes to the infant. The study aimed to estimate the public health burden
      resulting from adverse pregnancy outcomes due to syphilis infection among
      pregnant women not screened for syphilis in 43 countries in sub-Saharan Africa.
      METHODS: Estimated country-specific incidence of syphilis was generated from
      annual number of live births, the proportion of women with at least 1 antenatal
      care (ANC) visit, the syphilis prevalence rate, and the proportion of women
      screened for syphilis during ANC.Adverse pregnancy outcome data (stillbirth,
      neonatal death, low birth weight, and congenital syphilis) were obtained from
      published sources. Disability-adjusted life-year (DALY) estimates were calculated
      using undiscounted local life expectancy, the neonatal standard loss function,
      and relevant disability weights. The model assessed the potential impact of
      raising ANC coverage to at least 95% and syphilis screening to at least 95%
      (World Health Organization targets). RESULTS: For all 43 sub-Saharan Africa
      countries, the estimated incidence of adverse pregnancy outcomes was 205,901 (95%
      confidence interval [CI], 113,256-383,051) per year, including stillbirth (88,376
      [95% CI, 60,854-121,713]), neonatal death (34,959 [95% CI, 23,330-50,076]), low
      birth weight (22,483 [95% CI, 0-98,847]), and congenital syphilis (60,084 [95%
      CI, 29,073-112,414]), resulting in approximately 12.5 million DALYs. Countries
      with the greatest burden are (in DALYs, millions) Democratic Republic of the
      Congo (1.809), Nigeria (1.598), Ethiopia (1.466), and Tanzania (0.961). Attaining
      World Health Organization targets could reduce the burden by 8.5 million DALYs.
      CONCLUSIONS: Substantial infant mortality and morbidity results from maternal
      syphilis infection concentrated in countries with low access to ANC or low rates
      of syphilis screening.

PMID- 26222750
TI  - A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study
      Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the
      Treatment of Bacterial Vaginosis.
AB  - BACKGROUND: Bacterial vaginosis (BV), a prevalent infection in women of
      reproductive age, is associated with increased risk of upper genital tract and
      sexually transmitted infections, and complications in pregnancy. Currently
      approved treatments include metronidazole, which requires once or twice daily
      intravaginal administration for 5 days or twice daily oral administration for 7
      days. This phase 3 study determined the safety and efficacy of single-dose
      metronidazole vaginal gel (MVG) 1.3%. METHODS: In this double-blind, vehicle
      controlled study, 651 women with clinical diagnosis of BV were randomized 1:1 to
      receive MVG 1.3% or vehicle vaginal gel. Primary efficacy measure was clinical
      cure (normal discharge, negative "whiff test," and <20% clue cells) at day 21.
      Secondary measures included therapeutic cure (both clinical and bacteriological;
      day 21) and bacteriologic cure (Nugent score <4), clinical cure, and time to
      resolution of symptoms (day 7). RESULTS: A total of 487 participants were
      included in the primary analysis. Clinical and therapeutic cure rates (day 21)
      were higher in participants treated with MVG 1.3% compared with vehicle gel
      (37.2% vs. 26.6% [P = 0.010] and 16.8% vs. 7.2% [P = 0.001], respectively).
      Clinical and bacteriologic cure rates (day 7) were also higher in the MVG 1.3%
      group (46.0% vs. 20.0% [P < 0.001] and 32.7% vs. 6.3% [P < 0.001], respectively).
      The median time to resolution of symptoms was shorter in the MVG 1.3% (day 6)
      than vehicle group (not reached). No serious adverse events were reported, and
      incidence was similar across treatment groups. CONCLUSIONS: Single-dose MVG 1.3%
      was safe and superior to vehicle gel in producing cure among women with BV.

PMID- 26222751
TI  - Factors Associated With Hepatitis C Infection Among HIV-Infected Men Who Have Sex
      With Men With No Reported Injection Drug Use in New York City, 2000-2010.
AB  - BACKGROUND: Hepatitis C (HCV) infection is a major source of morbidity and
      mortality among HIV-infected patients. Despite decreasing HCV incidence in the
      United States, the proportion of cases among men who have sex with men (MSM)
      without history of injection drug use (IDU) in New York City has more than
      tripled between 2000 and 2010. METHODS: Using matched surveillance data, we
      identified non-IDU HIV-infected MSM with and without diagnosed HCV. Differences
      in continuous variables were assessed with Mann-Whitney U tests, and Pearson chi
      tests were used for categorical variables. Poisson regression was used to compare
      HCV diagnosis rates by race/ethnicity and sexual transmitted disease history.
      RESULTS: There were 41,303 non-IDU MSM diagnosed as having HIV before 2010 alive
      as of 2000, of whom 2016 (4.9%) were diagnosed as having HCV after HIV diagnosis.
      The HCV diagnosis rate was 605/100,000 person-years. Adjusting for birth year and
      age at HIV diagnosis, Hispanics (rate ratio [RR], 1.4; 95% confidence interval
      [CI], 1.2-1.5) and non-Hispanic blacks (RR, 1.6; 95% CI, 1.4-1.8) had higher HCV
      diagnosis rates than did non-Hispanic whites. Adjusting for race/ethnicity, birth
      year, and age at HIV diagnosis, MSM diagnosed as having syphilis (RR, 2.5; 95%
      CI, 2.3-2.8) had higher HCV diagnosis rates than did those without syphilis.
      CONCLUSIONS: We found a racial/ethnic disparity in HCV diagnosis rates and an
      association between HCV and syphilis, which is consistent with sexual
      transmission of HCV. With curative HCV treatment available, emphasis should be
      placed on adherence to guidelines recommending annual HCV screening for HIV
      infected MSM, and education and outreach to MSM to prevent sexually transmitted
      HCV infections.

PMID- 26222753
TI  - Consistency of Condom Use During Receptive Anal Intercourse Among Women and Men
      Who Have Sex With Men: Findings From the Safe in the City Behavioral Study.
AB  - BACKGROUND: Unprotected receptive anal intercourse poses HIV risk for men who
      have sex with men (MSM) and heterosexual women. Little is known about differences
      in consistent condom use during anal intercourse among these populations.
      METHODS: Data were analyzed from a nested study conducted from 2004 to 2005
      within a behavioral intervention trial of approximately 40,000 urban US sexually
      transmitted disease clinic patients. Analyses were restricted to women and MSM
      who reported receptive anal intercourse with at least 1 partner in the prior 3
      months at baseline, or 3-month follow-up surveys. Condom use was categorized as
      consistent (100% of receptive acts) or inconsistent/nonuse (0-99% of receptive
      acts). Multivariable regression with general estimating equations was used to
      identify factors associated with consistent condom use within each population.
      RESULTS: Approximately 31% of women and 70% of MSM reported receptive anal
      intercourse at least once in the past 3 months. Men who have sex with men were
      significantly more likely to report consistent condom use compared with women.
      For women, intention to use condoms, partner support for condom use, the belief
      they could stop having sex when condoms were unavailable, and believing their
      partner had not given them a sexually transmitted infection (STI) were associated
      with using condoms consistently. For MSM, intention to use condoms, condom use
      self-efficacy, perceived partner support for condom use, having a nonmain
      partner, believing their partner had not given them an STI, and fewer sex acts
      were associated with consistent condom use. CONCLUSIONS: Findings confirm the
      importance of considering anal intercourse when assessing STI/HIV risk in MSM and
      heterosexual women.

PMID- 26222752
TI  - Intimate Partner Violence and Correlates With Risk Behaviors and HIV/STI
      Diagnoses Among Men Who Have Sex With Men and Men Who Have Sex With Men and Women
      in China: A Hidden Epidemic.
AB  - BACKGROUND: Intimate partner violence (IPV) research has primarily focused on
      heterosexual couples but has largely ignored IPV among men who have sex with men
      (MSM). We examined IPV prevalence among MSM and men who have sex with men and
      women (MSMW) in China. METHODS: Men who have sex with men older than 16 years
      were recruited through 3 MSM-focused Web sites in China. An online survey
      containing items on sociodemographics, risk behaviors, IPV, and self-reported HIV
      or sexually transmitted infection diagnosis was completed. Multivariate
      regression was used to examine associations between IPV and risk behaviors and an
      HIV or sexually transmitted infection diagnosis. RESULTS: Among 610 participants,
      182 (29.8%) reported experiencing at least 1 type of IPV. Men who have sex with
      both men and women were at significantly greater risk for IPV (adjusted odds
      ratio [AOR], 1.65; 95% confidence interval [CI], 1.08-2.53) compared with MSM.
      Men who had experienced IPV were more likely to have participated in group sex
      (AOR, 1.86; 95% CI, 1.08-3.21), to have had sex in exchange for gifts or money
      (AOR, 5.06; 95% CI, 2.47-10.35), and to report a positive HIV diagnosis (AOR,
      2.59; 95% CI, 1.22-5.51). CONCLUSIONS: There is a hidden epidemic of IPV among
      MSM in China, especially among MSMW. The hidden nature of MSM and MSMW suggests
      the need for a clinical environment more conducive to disclosure. Research is
      needed to understand the pathways linking IPV and HIV risk among MSM to optimize
      the design of effective interventions.

PMID- 26222754
TI  - Response to: "What Can We Infer About Incarceration and Sexually Transmitted
      Diseases?".

PMID- 26222755
TI  - One Size Does Not Fit All: The Public Health Ramifications of Proposed Food and
      Drug Administration Premarket Review for Extragenital Gonorrhea and Chlamydia
      Testing.

PMID- 26222756
TI  - Defining the Scope of Sexually Transmitted Hepatitis C Virus Epidemic Among HIV
      Infected Men Who Have Sex With Men in New York City.

PMID- 26222758
TI  - Enhanced Charge Separation Efficiency in Pyridine-Anchored Phthalocyanine
      Sensitized Solar Cells by Linker Elongation.
AB  - A series of zinc phthalocyanine sensitizers (PcS22-24) having a pyridine
      anchoring group are designed and synthesized to investigate the structural
      dependence on performance in dye-sensitized solar cells. The pyridine-anchor zinc
      phthalocyanine sensitizer PcS23 shows 79 % incident-photon to current-conversion
      efficiency (IPCE) and 6.1 % energy conversion efficiency, which are comparable
      with similar phthalocyanine dyes having a carboxylic acid anchoring group. Based
      on DFT calculations, the high IPCE is attributed with the mixture of an excited
      state molecular orbital of the sensitizer and the orbitals of TiO2 . Between
      pyridine and carboxylic acid anchor dyes, opposite trends are observed in the
      linker-length dependence of the IPCE. The red-absorbing PcS23 is applied for co
      sensitization with a carboxyl-anchor organic dye D131 that has a complementary
      spectral response. The site-selective adsorption of PcS23 and D131 on the TiO2
      surface results in a panchromatic photocurrent response for the whole visible
      light region of sun light. 

PMID- 26222759
TI  - The Effect of Lavender Oil in Patients with Renal Colic: A Prospective Controlled
      Study Using Objective and Subjective Outcome Measurements.
AB  - OBJECTIVE: To assess the usability of lavender oil as an adjuvant in the medical
      treatment of pain due to renal stones. METHODS: One hundred patients age 19-64
      years diagnosed with renal colic were included in the study. Group 1 (n=50)
      received standard medical therapy (diclofenac sodium, 75 mg intramuscularly);
      group 2 (n=50) received aromatherapy (lavender oil) in addition to the standard
      medical treatment. In both groups, the severity of the pain was graded between 0
      (no pain) and 10 (severe pain) by using the visual analogue scale (VAS). RESULTS:
      The VAS values at the beginning and at 10 and 30 minutes in group 1 were 7.70+/
      1.61, 5.02+/-2.20, and 2.89+/-1.96, respectively; in group 2, the values were
      7.83+/-2.02, 4.42+/-2.46, and 2.20+/-1.74, respectively. The VAS values for the
      male patients in group 1 at the beginning and at 10 and 30 minutes were 7.61+/
      1.47, 4.80+/-2.00, and 2.67+/-1.74; in the female patients, the values were
      7.81+/-1.80, 5.40+/-2.41, and 3.72+/-1.94. For the male patients in group 2, the
      VAS values at the beginning and at 10 and 30 minutes were 8.25+/-2.01, 4.93+/
      2.72, and 2.96+/-1.90, respectively; for the female patients, the values were
      7.52+/-1.94, 4.15+/-1.95, and 1.21+/-0.91, respectively. Results are presented as
      mean+/-SD. Although there was no significant difference between the VAS values at
      the beginning and at 10 minutes in both groups, the VAS values at 30 minutes in
      the group receiving aromatherapy plus conventional treatment were statistically
      significantly low. CONCLUSION: These findings suggest that the use of
      aromatherapy, which is a nonpharmacologic treatment method, as an adjuvant to
      conventional treatment methods will help decrease pain, particularly in female
      patients.

PMID- 26222760
TI  - Fever pattern and C-reactive protein predict response to rescue therapy in
      Kawasaki disease.
AB  - BACKGROUND: Evidence to guide rescue therapy in refractory Kawasaki disease (KD)
      is lacking. The aim of this study was to determine the most important variables
      in predicting non-response to rescue therapy in refractory KD. METHODS: We
      retrospectively analyzed 171 patients diagnosed with refractory KD resistant to
      initial i.v. immunoglobulin (IVIG). Participants received rescue therapy
      consisting of IVIG monotherapy or IVIG plus prednisolone. Characteristics and
      laboratory variables were compared between rescue therapy non-responders and
      responders. Multivariate logistic regression analysis was performed to determine
      the independent predictors of non-response to rescue therapy. RESULTS: Among the
      171 participants, 54 (31.6%) were non-responders to rescue therapy. On univariate
      analysis, fever pattern after initial IVIG, day of illness at rescue therapy,
      rescue therapy regimen and six laboratory variables (pre-IVIG sodium, C-reactive
      protein [CRP]; post-IVIG white blood cell count, platelet count, sodium, CRP)
      were useful in discriminating between non-responders and responders. These nine
      variables were included in multivariate logistic regression analysis. Persistent
      fever after initial IVIG (aOR, 2.39; 95%CI: 1.07-5.37) and post-IVIG CRP (aOR,
      1.09; 95%CI: 1.02-1.17, per 1 mg/dL increase) were identified as independent
      predictors of non-response to rescue therapy. IVIG rescue monotherapy (aOR, 3.05;
      95%CI: 1.05-8.84) also predicted non-response after adjusting for fever pattern
      and post-IVIG CRP. CONCLUSIONS: Persistent fever and elevated CRP after initial
      IVIG are predictive of non-response to rescue therapy for refractory KD. For
      patients at high risk of non-response, IVIG plus prednisolone, or even further
      intensified rescue therapy regimens may be preferable.

PMID- 26222757
TI  - Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice
      Guideline.
AB  - OBJECTIVE: The objective is to formulate clinical practice guidelines for
      treating Cushing's syndrome. PARTICIPANTS: Participants include an Endocrine
      Society-appointed Task Force of experts, a methodologist, and a medical writer.
      The European Society for Endocrinology co-sponsored the guideline. EVIDENCE: The
      Task Force used the Grading of Recommendations, Assessment, Development, and
      Evaluation system to describe the strength of recommendations and the quality of
      evidence. The Task Force commissioned three systematic reviews and used the best
      available evidence from other published systematic reviews and individual
      studies. CONSENSUS PROCESS: The Task Force achieved consensus through one group
      meeting, several conference calls, and numerous e-mail communications. Committees
      and members of The Endocrine Society and the European Society of Endocrinology
      reviewed and commented on preliminary drafts of these guidelines. CONCLUSIONS:
      Treatment of Cushing's syndrome is essential to reduce mortality and associated
      comorbidities. Effective treatment includes the normalization of cortisol levels
      or action. It also includes the normalization of comorbidities via directly
      treating the cause of Cushing's syndrome and by adjunctive treatments (eg,
      antihypertensives). Surgical resection of the causal lesion(s) is generally the
      first-line approach. The choice of second-line treatments, including medication,
      bilateral adrenalectomy, and radiation therapy (for corticotrope tumors), must be
      individualized to each patient.

PMID- 26222761
TI  - Glycoprofiling effects of media additives on IgG produced by CHO cells in fed
      batch bioreactors.
AB  - Therapeutic monoclonal antibodies (mAbs) are mainly produced by heterologous
      expression in Chinese hamster ovary (CHO) cells. The glycosylation profile of the
      mAbs has major impact on the efficacy and safety of the drug and is therefore an
      important parameter to control during production. In this study, the effect on
      IgG N-glycosylation from feeding CHO cells with eight glycosylation precursors
      during cultivation was investigated. The study was conducted in fed-batch mode in
      bioreactors with biological replicates to obtain highly controlled and comparable
      conditions. We assessed charge heterogeneity and glycosylation patterns of IgG.
      None of the eight feed additives caused statistically significant changes to cell
      growth or IgG productivity, compared to controls. However, the addition of 20 mM
      galactose did result in a reproducible increase of galactosylated IgG from 14% to
      25%. On the other hand, addition of 20 mM N-acetyl-D-glucosamine (GlcNAc) reduced
      relative abundance of galactosylated IgG by 4%. Additionally, supplementation
      with 10 mM mannose slightly reduced GlcNAc occupancy of IgG. Overall, comparing
      the effects of IgG glycosylation, by supplementing the cell culture medium with
      glycosylation precursors during cultivation, revealed an application of these
      glycosylation precursors for modulating N-glycosylation of IgG.

PMID- 26222762
TI  - Investigation of Low Heat Accumulation Asphalt Mixture and Its Impact on Urban
      Heat Environment.
AB  - This study is focused on investigating the effectiveness of low heat accumulation
      asphalt mixture and its impact on the urban heat environment. Infrared radiation
      experiments showed that the temperature of the asphalt mixture decreased with the
      increase in far-infrared radiant material. The results also revealed that,
      compared to asphalt with 0% far-infrared radiant content, the asphalt material
      with a certain ratio of far-infrared radiation material had higher stability at
      high and low temperatures as well as good water absorption capacity. The Marshall
      stability of the specimen mixed with 6% far-infrared radiant was higher by 12.2%
      and had a residual stability of up to 98.9%. Moreover, the low-temperature
      splitting tensile strength of the asphalt mixture with 6% far-infrared radiation
      material increased by 21.3%. The friction coefficient of the asphalt mixtures
      with 6% and 12% far-infrared radiation material increased by 17.7% and 26.9%,
      respectively. 

PMID- 26222763
TI  - CTO, A Challenge Not Only for PCI, But Also for EP.

PMID- 26222765
TI  - Assessment of tissue levels of dickkopf-1 in androgenetic alopecia and alopecia
      areata.
AB  - BACKGROUND: Androgenetic alopecia (AGA) is the commonest form of hair loss in
      men. Alopecia areata (AA) is an organ-specific autoimmune disease. Studies
      revealed that Dickkopf 1 (DKK-1), a powerful suppressor of the Wnt/beta-catenin
      signaling pathway, induced anagen-to-catagen transition in mice. Moreover, in
      vitro studies suggested that DKK-1 played a role in dihydrotestosterone (DHT)
      induced balding. AIM: To evaluate the tissue levels of DKK-1 in patients with AGA
      and AA, to assess its possible role as a pathogenetic mechanism in both
      disorders. METHODS: This study included 24 patients with AGA, 31 patients with
      AA, and 33 healthy controls. Scalp biopsies were taken from all participants for
      the detection of tissue DKK-1 levels. RESULTS: Tissue DKK-1 levels were
      significantly higher in patients with AGA than in controls (P = 0.000) as well as
      in patients with AA than in controls (P = 0.001). In addition, they were
      significantly higher in patients with AGA than in patients with AA (P = 0.000).
      DKK-1 was higher in male than in female patients with AGA. DKK-1 was negatively
      correlated with disease duration in AGA. CONCLUSION: In conclusion, this study
      suggests an important role for DKK-1 in the pathogenesis of AGA and AA through
      documenting higher tissue DKK-1 levels in patients with both hair disorders
      compared to controls and suggests that DKK-1 may be a promising therapeutic
      target for these hair diseases.

PMID- 26222764
TI  - Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer
      on eligibility for breast-conserving surgery and breast conservation rates:
      surgical results from CALGB 40603 (Alliance).
AB  - OBJECTIVE: To assess the efficacy of neoadjuvant systemic therapy (NST) at
      increasing the rate of successful breast-conserving therapy (BCT) in triple
      negative breast cancer. BACKGROUND: Inducing tumor regression to permit BCT is
      often cited to support administration of NST. To quantify this benefit, we
      conducted a surgical companion study to CALGB40603, a randomized phase II, 2*2
      factorial trial of neoadjuvant paclitaxel +/- carboplatin +/- bevacizumab (B)
      followed by doxorubicin plus cyclophosphamide +/- B in stage II-III triple
      negative breast cancer. METHODS: Before and after NST, treating surgeons
      evaluated BCT candidacy by clinico-radiographic criteria; surgery performed was
      at surgeon and patient discretion. We measured (1) conversion rates from BCT
      ineligible to BCT-eligible, (2) surgical choices in BCT candidates, and (3) rates
      of successful BCT with tumor-free margins. RESULTS: Four hundred four patients
      were assessable for surgical outcomes. Two hundred nineteen (54%) were BCT
      candidates before NST. One hundred ninety-seven (90%) remained BCT candidates
      after NST, of whom 138 (70%) chose BCT, which was successful in 130 (94%). Of 185
      (46%) who were not BCT candidates before NST, 78 (42%) converted to candidates
      with NST. Of these, 53 (68%) chose BCT with a 91% (48/53) success rate. The
      overall BCT-eligibility rate rose from 54% to 68% (275/404) with NST. Addition of
      carboplatin, B, or both increased conversion rates. CONCLUSIONS: This is the
      first study to document prospectively a 42% conversion rate from BCT-ineligible
      to BCT-eligible, resulting in a 14% absolute increase in BCT eligibility. BCT was
      successful in 93% of patients who opted for it, but 31% of BCT-eligible patients
      still chose mastectomy.

PMID- 26222766
TI  - Scenedesmus dimorphus (Turpin) Kutzing growth with digestate from biogas plant in
      outdoor bag photobioreactors.
AB  - Digestate coming from an Anaerobic Digestion unit in a Biogas Plant, feeded on
      cow manure and vegetable waste from markets, has been used. About 8-35 L
      polyethylene transparent bags have been employed as cultivation container,
      outdoor. Different aliquots of digestate, alone or mixed with commercial liquid
      fertiliser, were employed to cultivate in batch Scenedesus dimorphus, a
      freshwater green microalga, in the ENEA facilities of Casaccia Research Center,
      near Rome, Italy. The cultivation period was June-July 2013. The average daily
      yields of dry microalgae biomass varied from 20 mg/L/d to 60 mg/L/d, mean 38.2
      mg/L/d. Final dry biomass concentration varied from 0.18 to 1.29 g/L, mean 0.55
      g/L. S. dimorphus proved to be very efficient in removing N and P from the
      culture medium. Another fact emerged from these trials is that S. dimorphus inner
      composition resulted to be variable in response to the tested different culture
      conditions.

PMID- 26222767
TI  - Fuchs' Uveitis Syndrome: No Longer a Syndrome?
AB  - PURPOSE: Rubella virus (RV) has a central role in the etiopathogenesis of Fuchs'
      uveitis syndrome (FUS). We aim to offer new insights by comprehensive analysis of
      recent laboratory and epidemiologic data. METHODS: We conducted a literature
      search for laboratory data and papers on etiopathogenesis. RESULTS: Aqueous
      humour samples of FUS patients show immunoreactivity to RV, in a specific and
      sensitive manner. Identification of RV genome confirm intraocular infection in a
      subset of FUS patients. Epidemiologic findings further support causality. The
      clinical spectrum of RV-associated uveitis is similar but not identical to FUS.
      FUS eyes exhibit a predominance of CD8 + T cells, high IFN-? and IL-10 levels.
      CONCLUSIONS: RV is the leading cause of FUS. Cytokine-based findings mirror a
      viral etiology and chronic low-grade inflammation. RV-associated FUS represents a
      common pathway of intraocular RV inoculation after congenital or acquired
      infection. Other causes, including HSV and CMV, may lead to FUS.

PMID- 26222768
TI  - Anti-Bioadhesive Coating Based on Easy to Make Pseudozwitterionic RAFT Block
      Copolymers for Blood-Contacting Applications.
AB  - Amphiphilic diblock copolymer containing randomly distributed positive and
      negative charged monomers are synthesized using RAFT polymerization technique to
      be used as anti-bioadhesion coatings for hydrophobic surfaces. Quaternized 2
      (dimethylamino) ethyl methacrylate and potassium 3-sulfopropyl methacrylate
      (P[qDMAEMA-co-KSPMA]) are randomly polymerized to yield an anti-bioadhesion block
      which is, in one pot, copolymerized with styrene as an anchoring block. This
      copolymer has demonstrated high anti-bioadhesion properties to avoid the blood
      clotting in medical devices through a simple and facile approach to preparation
      of pseudozwitterionic copolymers. 

PMID- 26222769
TI  - Enhanced Fracture Resistance of Flexible ZnO:Al Thin Films in Situ Sputtered on
      Bent Polymer Substrates.
AB  - Improving the fracture resistance of inorganic thin films is one of the key
      challenges in flexible electronic devices. A nonconventional in situ sputtering
      method is introduced to induce residual compressive stress in ZnO:Al thin films
      during deposition on a bent polymer substrate. The films grown under a larger
      prebending strain resulted in a higher fracture resistance to applied strains by
      exhibiting a ~ 70% improvement in crack-initiating critical strain compared with
      the reference sample grown without bending. This significant improvement is
      attributed to the induced residual stress, which helps to prevent the formation
      of cracks by counteracting the applied strain. 

PMID- 26222770
TI  - Never underestimate inflammatory bowel disease: High prevalence rates and
      confirmation of high incidence rates in Australia.
AB  - BACKGROUND AND AIMS: Regional variations in inflammatory bowel disease (IBD)
      rates have been observed. Limited epidemiological data are available from
      Australasia. IBD prevalence rates have never been assessed in an Australian
      population-based setting. In addition, there are few historical IBD incidence
      data to allow assessment of rate changes. The aims were to calculate Australia's
      first population-based IBD prevalence rates, to reassess local IBD incidence
      rates, and to establish a population-based inception cohort. METHODS: An
      observational, prospective population-based epidemiological study was performed
      to assess IBD prevalence and incidence rates from July 2010 to June 2011 in a
      geographically defined Australian population (Barwon, Victoria). RESULTS: There
      were 1011 prevalent IBD cases identified, representing a crude point prevalence
      rate of 344.6 per 100,000 on June 30, 2011. Crohn's disease was the most common
      prevalent subtype. Seventy-one incident cases of IBD were identified, with a
      crude incidence rate of 24.2 per 100,000. Crohn's disease was again more common.
      Local incidence rates have not changed between 2007 and the present study. All
      incident cases were successfully incorporated into an inception cohort.
      CONCLUSION: The burden of IBD in our local region is high. Demographic
      similarities allow these results to be applied to the broader Australian
      community. We propose that the number of existing and new cases each year in
      Australia has been previously underestimated. These revised figures will be
      important when planning the provision of health resources for these patients in
      the future and when assessing need for research funding priorities.

PMID- 26222771
TI  - Fetal and Perinatal Mortality: United States, 2013.
AB  - OBJECTIVES: This report presents 2013 fetal and perinatal mortality data by
      maternal age, marital status, race, Hispanic origin, and state of residence, as
      well as by fetal birthweight, gestational age, plurality, and sex. Trends in
      fetal and perinatal mortality are also examined. METHODS: Descriptive tabulations
      of data are presented and interpreted. RESULTS: A total of 23,595 fetal deaths at
      20 weeks of gestation or more were reported in the United States in 2013. The
      U.S. fetal mortality rate was 5.96 fetal deaths at 20 weeks of gestation or more
      per 1,000 live births and fetal deaths, not significantly different from the rate
      of 6.05 in 2012. The lack of decline in fetal mortality in recent years, coupled
      with declines in infant mortality, meant that more fetal deaths than infant
      deaths occurred in the United States for 2011-2013 (although the rates were
      essentially the same). In 2013, the fetal mortality rate for non-Hispanic black
      women (10.53) was more than twice the rate for non-Hispanic white (4.88) and
      Asian or Pacific Islander (4.68) women. The rate for American Indian or Alaska
      Native women (6.22) was 27% higher, and the rate for Hispanic women (5.22) was 7%
      higher, than the rate for non-Hispanic white women. Fetal mortality rates were
      highest for teenagers, women aged 35 and over, unmarried women, and women with
      multiple pregnancies.

PMID- 26222772
TI  - Smartphone Use for Cervical Cancer Screening in Low-Resource Countries: A Pilot
      Study Conducted in Madagascar.
AB  - BACKGROUND: Visual inspection of the cervix after application of 5% acetic acid
      (VIA) is a screening technique for cervical cancer used widely in low and middle
      income countries (LMIC). To improve VIA screening performance, digital images
      after acid acetic application (D-VIA) are taken. The aim of this study was to
      evaluate the use of a smartphone for on- and off-site D-VIA diagnosis. MATERIALS
      AND METHODS: Women aged 30-65 years, living in the city of Ambanja, Madagascar,
      were recruited through a cervical cancer screening campaign. Each performed a
      human papillomavirus (HPV) self-sample as a primary screen. Women testing
      positive for HPV were referred for VIA followed by D-VIA, cervical biopsy and
      endocervical curettage according to routine protocol. In addition, the same day,
      the D-VIA was emailed to a tertiary care center for immediate assessment. Results
      were scored as either D-VIA normal or D-VIA abnormal, requiring immediate therapy
      or referral to a tertiary center. Each of the three off-site physicians were
      blinded to the result reported by the one on-site physician and each gave their
      individual assessment followed by a consensus diagnosis. Statistical analyses
      were conducted using STATA software. RESULTS: Of the 332 women recruited, 137
      (41.2%) were HPV-positive and recalled for VIA triage; compliance with this
      invitation was 69.3% (n = 95). Cervical intraepithelial neoplasia was detected in
      17.7% and 21.7% of digital images by on-site and off-site physicians,
      respectively. The on-site physician had a sensitivity of 66.7% (95%CI: 30.0-90.3)
      and a specificity of 85.7% (95%CI: 76.7-91.6); the off-site physician consensus
      sensitivity was 66.7% (95%CI: 30.0-90.3) with a specificity of 82.3% (95%CI: 72.4
      89.1). CONCLUSION: This pilot study supports the use of telemedicine for off-site
      diagnosis of cervical intraepithelial neoplasia, with diagnostic performance
      similar to those achieved on-site. Further studies need to determine if
      smartphones can improve cervical cancer screening efficiency in LMIC.

PMID- 26222773
TI  - [N-Methyl-2-pyrrolidone][C1-C4 carboxylic acid]: a novel solvent system with
      exceptional lignin solubility.
AB  - Novel solvent systems composed of N-methyl-2-pyrrolidone and C1-C4 carboxylic
      acid exhibit unique physicochemical properties, e.g. large polarity, low
      viscosity and excellent hydrogen bonding capacity, which have demonstrated
      excellent lignin solubility that outperforms conventional solvents and ionic
      liquids. 

PMID- 26222774
TI  - Elevated Circulating Osteoprotegerin and Renal Dysfunction Predict 15-Year
      Cardiovascular and All-Cause Mortality: A Prospective Study of Elderly Women.
AB  - BACKGROUND: Data on the predictive role of estimated glomerular filtration rate
      (eGFR) and osteoprotegerin (OPG) for cardiovascular (CVD) and all-cause mortality
      risk have been presented by our group and others. We now present data on the
      interactions between OPG with stage I to III chronic kidney disease (CKD) for all
      cause and CVD mortality. METHODS AND RESULTS: The setting was a 15-year study of
      1,292 women over 70 years of age initially randomized to a 5-year controlled
      trial of 1.2 g of calcium daily. Serum OPG and creatinine levels with complete
      mortality records obtained from the Western Australian Data Linkage System were
      available. Interactions were detected between OPG levels and eGFR for both CVD
      and all-cause mortality (P < 0.05). Compared to participants with eGFR >=60
      ml/min/1.73 m2 and low OPG, participants with eGFR of <60 ml/min/1.73 m2 and
      elevated OPG had a 61% and 75% increased risk of all-cause and CVD mortality
      respectively (multivariate-adjusted HR, 1.61; 95% CI, 1.27-2.05; P < 0.001 and
      HR, 1.75; 95% CI, 1.22-2.55; P = 0.003). This relationship with mortality was
      independent of decline in renal function (P<0.05). Specific causes of death in
      individuals with elevated OPG and stage III CKD highlighted an excess of coronary
      heart disease, renal failure and chronic obstructive pulmonary disease deaths (P
      < 0.05). CONCLUSION: The association between elevated OPG levels with CVD and all
      cause mortality was more evident in elderly women with poorer renal function.
      Assessment of OPG in the context of renal function may be important in studies
      investigating its relationship with all-cause and CVD mortality.

PMID- 26222775
TI  - Structural Characterization of Single-Stranded DNA Monolayers Using Two
      Dimensional Sum Frequency Generation Spectroscopy.
AB  - DNA-covered materials are important in technological applications such as
      biosensors and microarrays, but obtaining structural information on surface-bound
      biomolecules is experimentally challenging. In this paper, we structurally
      characterize single-stranded DNA monolayers of poly(thymine) from 10 to 25 bases
      in length with an emerging surface technique called two-dimensional sum frequency
      generation (2D SFG) spectroscopy. These experiments are carried out by adding a
      mid-IR pulse shaper to a femtosecond broad-band SFG spectrometer. Cross peaks and
      2D line shapes in the 2D SFG spectra provide information about structure and
      dynamics. Because the 2D SFG spectra are heterodyne detected, the monolayer
      spectra can be directly compared to 2D infrared (2D IR) spectra of poly(thymine)
      in solution, which aids interpretation. We simulate the 2D SFG spectra using DFT
      calculations and an excitonic Hamiltonian that relates the molecular geometry to
      the vibrational coupling. Intrabase cross peaks help define the orientation of
      the bases and interbase cross peaks, created by coupling between bases, and
      resolves features not observed in 1D SFG spectra that constrain the relative
      geometries of stacked bases. We present a structure for the poly(T) oligomer that
      is consistent with the 2D SFG data. These experiments provide insight into the
      DNA monolayer structure and set precedent for studying complex biomolecules on
      surfaces with 2D SFG spectroscopy. 

PMID- 26222776
TI  - Community Mobilization and Readiness: Planning Flaws which Challenge Effective
      Implementation of 'Communities that Care' (CTC) Prevention System.
AB  - This article reviews the experience of implementing a community approach to drug
      use and youth delinquency prevention based on the 'Communities that Care' (CTC)
      system implemented in one Croatian county consisting of 12 communities, 2002 to
      2013 (Hawkins, 1999; Hawkins & Catalano, 2004). This overview explores selected
      critical issues which are often not considered in substance use(r) community
      intervention planning, implementation as well as in associated process and
      outcome assessments. These issues include, among others, the mobilization process
      of adequate representation of people; the involvement of relevant key individual
      and organizational stakeholders and being aware of the stakeholders' willingness
      to participate in the prevention process. In addition, it is important to be
      aware of the stakeholders' knowledge and perceptions about the 'problems' of drug
      use and youth delinquency in their communities as well as the characteristics of
      the targeted population(s). Sometimes there are community members and
      stakeholders who block needed change and therefore prevention process enablers
      and 'bridges' should be involved in moving prevention programming forward.
      Another barrier that is often overlooked in prevention planning is community
      readiness to change and a realistic assessment of available and accessible
      resources for initiating the planned change(s) and sustaining them. All of these
      issues have been found to be potentially related to intervention success. At the
      end of this article, I summarize perspectives from prevention scientists and
      practitioners and lessons learned from communities' readiness research and
      practice in Croatian that has international relevance. 

PMID- 26222777
TI  - Comparative Pharmacokinetics and Allometric Scaling of Carboplatin in Different
      Avian Species.
AB  - The use of chemotherapeutics as a possible treatment strategy in avian oncology
      is steadily increasing over the last years. Despite this, literature reports
      regarding dosing strategies and pharmacokinetic behaviour of chemotherapeutics in
      avian species are lacking. The aim of the present study was to investigate the
      pharmacokinetics of carboplatin in a representative species of the order of
      Galliformes, Anseriformes, Columbiformes and Psittaciformes. Eight chickens,
      ducks and pigeons and twenty-eight parakeets were administered carboplatin
      intravenously (5 mg/kg body weight). A specific and sensitive liquid
      chromatography-tandem mass spectrometry method was developed and validated for
      quantification of the free carboplatin in plasma of the four birds species (limit
      of quantification: 20 ng/mL for chicken and duck, 50 ng/mL for pigeon and 100
      ng/mL for parakeets). Non-compartmental pharmacokinetic analysis and allometric
      scaling demonstrated a significant correlation (R2 = 0.9769) between body weight
      (BW) and elimination half-life (T1/2el). T1/2el ranged from 0.41 h in parakeets
      (BW: 61 +/- 8 g) to 1.16 h chickens (BW: 1909 +/- 619 g). T1/2el is a good
      parameter for dose optimization of carboplatin in other avian species, since also
      the previously reported T1/2el in cockatoos (average BW: 769 +/- 68 g) of 1.00 h
      corresponds to the results obtained in the present study. 

PMID- 26222778
TI  - An Integrative Approach for Mapping Differentially Expressed Genes and Network
      Components Using Novel Parameters to Elucidate Key Regulatory Genes in Colorectal
      Cancer.
AB  - For examining the intricate biological processes concerned with colorectal cancer
      (CRC), a systems biology approach integrating several biological components and
      other influencing factors is essential to understand. We performed a
      comprehensive system level analysis for CRC which assisted in unravelling crucial
      network components and many regulatory elements through a coordinated view. Using
      this integrative approach, the perceptive of complexity hidden in a biological
      phenomenon is extensively simplified. The microarray analyses facilitated
      differential expression of 631 significant genes employed in the progression of
      disease and supplied interesting associated up and down regulated genes like jun,
      fos and mapk1. The transcriptional regulation of these genes was deliberated
      widely by examining transcription factors such as hnf4, nr2f1, znf219 and dr1
      which directly influence the expression. Further, interactions of these
      genes/proteins were evaluated and crucial network motifs were detected to
      associate with the pathophysiology of CRC. The available standard statistical
      parameters such as z-score, p-value and significance profile were explored for
      the identification of key signatures from CRC pathway whereas a few novel
      parameters representing over-represented structures were also designed in the
      study. The applied approach revealed 5 key genes i.e. kras, araf, pik3r5, ralgds
      and akt3 via our novel designed parameters illustrating high statistical
      significance. These novel parameters can assist in scrutinizing candidate markers
      for diseases having known biological pathways. Further, investigating and
      targeting these proposed genes for experimental validations, instead being
      spellbound by the complicated pathway will certainly endow valuable insight in a
      well-timed systematic understanding of CRC.

PMID- 26222779
TI  - Isolation, Characterization, and Synthesis of the Barrettides: Disulfide
      Containing Peptides from the Marine Sponge Geodia barretti.
AB  - Two disulfide-containing peptides, barrettides A (1) and B (2), from the cold
      water marine sponge Geodia barretti are described. Those 31 amino acid residue
      long peptides were sequenced using mass spectrometry methods and structurally
      characterized using NMR spectroscopy. The structure of 1 was confirmed by total
      synthesis using the solid-phase peptide synthesis approach that was developed.
      The two peptides were found to differ only at a single position in their
      sequence. The three-dimensional structure of 1 revealed that these peptides
      possess a unique fold consisting of a long beta-hairpin structure that is cross
      braced by two disulfide bonds in a ladder-like arrangement. The peptides are
      amphipathic in nature with the hydrophobic and charged residues clustered on
      separate faces of the molecule. The barrettides were found not to inhibit the
      growth of either Escherichia coli or Staphylococcus aureus but displayed
      antifouling activity against barnacle larvae (Balanus improvisus) without lethal
      effects in the concentrations tested. 

PMID- 26222780
TI  - Hit or Miss: Fertilization Outcomes of Natural Inseminations by Japanese Quail.
AB  - Variation in fertilization success underlies sexual selection, yet mating does
      not guarantee fertilization. The relationship between natural inseminations and
      fertilization success is essential for understanding sexual selection, yet that
      relationship and its underlying mechanisms are poorly understood in sperm-storing
      vertebrates such as birds. Here the relationship is analyzed in mating trials
      using Japanese quail (Coturnix japonica), which show striking variation in the
      fertilizing success of inseminations. Failures of males' inseminations to
      fertilize eggs were mainly due to failures prior to sperm-egg contact.
      Fertilization probabilities on any given day were unrelated to whether the female
      had laid an egg the previous day, arguing against stimulation of sperm release
      from sperm storage tubules by the events of the daily egg-laying cycle. Instead,
      an unfertilized egg laid between two fertilized eggs predicted a longer sperm
      storage interval. Both sexes gained similar numbers of fertilized eggs by mating
      with a second partner the next day, but males, unlike females in a previous
      study, did not gain by having two females to mate with at the same time. Instead,
      they were both behaviorally and sperm limited, whereas females gain by mating
      twice in quick succession. Even double inseminations often failed to fertilize
      any eggs, and multiple matings would be needed for an entire clutch to be
      fertilized with high certainty. Paradoxically, this low and probabilistic
      fertilization success co-occurs with other notable characteristics of male quail
      suggestive of past sexual selection for increased success, including vigorous
      copulatory behavior, forced copulations, foamy secretion aiding in sperm
      competition, large testes and unusual sperm morphology. 

PMID- 26222781
TI  - When maladaptive gene flow does not increase selection.
AB  - Populations receiving high maladaptive gene flow are expected to experience
      strong directional selection-because gene flow pulls mean phenotypes away from
      local fitness peaks. We tested this prediction by means of a large and replicated
      mark-recapture study of threespine stickleback (Gasterosteus aculeatus) in two
      stream populations. One of the populations (outlet) experiences high gene flow
      from the lake population and its morphology is correspondingly poorly adapted.
      The other population (inlet) experiences very low gene flow from the lake
      population and its morphology is correspondingly well adapted. Contrary to the
      above prediction, selection was not stronger in the outlet than in the inlet, a
      result that forced us to consider potential reasons for why maladaptive gene flow
      might not increase selection. Of particular interest, we show by means of a
      simple population genetic model that maladaptive gene flow can-under reasonable
      conditions-decrease the strength of directional selection. This outcome occurs
      when immigrants decrease mean fitness in the resident population, which decreases
      the strength of selection against maladapted phenotypes. We argue that this
      previously unrecognized effect of gene flow deserves further attention in
      theoretical and empirical studies. 

PMID- 26222782
TI  - Plausible underpinnings of ventricular free wall rupture in patients with
      Takotsubo syndrome.

PMID- 26222783
TI  - Epicardial fat and coronary atherosclerosis: the effect of autonomic nervous
      system function.

PMID- 26222784
TI  - Visualization of Sensory Neurons and Their Projections in an Upper Motor Neuron
      Reporter Line.
AB  - Visualization of peripheral nervous system axons and cell bodies is important to
      understand their development, target recognition, and integration into complex
      circuitries. Numerous studies have used protein gene product (PGP) 9.5 [a.k.a.
      ubiquitin carboxy-terminal hydrolase L1 (UCHL1)] expression as a marker to label
      sensory neurons and their axons. Enhanced green fluorescent protein (eGFP)
      expression, under the control of UCHL1 promoter, is stable and long lasting in
      the UCHL1-eGFP reporter line. In addition to the genetic labeling of
      corticospinal motor neurons in the motor cortex and degeneration-resistant spinal
      motor neurons in the spinal cord, here we report that neurons of the peripheral
      nervous system are also fluorescently labeled in the UCHL1-eGFP reporter line.
      eGFP expression is turned on at embryonic ages and lasts through adulthood,
      allowing detailed studies of cell bodies, axons and target innervation patterns
      of all sensory neurons in vivo. In addition, visualization of both the sensory
      and the motor neurons in the same animal offers many advantages. In this report,
      we used UCHL1-eGFP reporter line in two different disease paradigms: diabetes and
      motor neuron disease. eGFP expression in sensory axons helped determine changes
      in epidermal nerve fiber density in a high-fat diet induced diabetes model. Our
      findings corroborate previous studies, and suggest that more than five months is
      required for significant skin denervation. Crossing UCHL1-eGFP with hSOD1G93A
      mice generated hSOD1G93A-UeGFP reporter line of amyotrophic lateral sclerosis,
      and revealed sensory nervous system defects, especially towards disease end
      stage. Our studies not only emphasize the complexity of the disease in ALS, but
      also reveal that UCHL1-eGFP reporter line would be a valuable tool to visualize
      and study various aspects of sensory nervous system development and degeneration
      in the context of numerous diseases. 

PMID- 26222786
TI  - Depressive-like behaviours and decreased dendritic branching in the medial
      prefrontal cortex of mice with tumors: A novel validated model of cancer-induced
      depression.
AB  - Depression is commonly comorbid in cancer patients and has detrimental effects on
      disease progression. Evidence suggests that biological mechanisms may induce the
      onset of cancer-induced depression (CID). The present investigation aims to
      establish a validated preclinical animal model of CID. Female BALB/c mice were
      allocated to four groups: control (n=12), chronic oral exposure to corticosterone
      (CORT) (n=12), CORT exposure followed by chronic low dose fluoxetine (FLX)
      treatment (n=12), and subcutaneous inoculation of 4T1 mammary carcinoma cells
      (n=13). Anhedonia was evaluated using the sucrose preference test (SPT), and
      behavioural despair was evaluated using the forced swim test (FST) and tail
      suspension test (TST). Sholl analyses were used to examine the dendritic
      morphology of Golgi-Cox impregnated neurons from the medial prefrontal cortex
      (mPFC). CORT exposure and tumor burden were both associated with decreased
      sucrose preference, increased FST immobility, and decreased basilar and apical
      dendritic branching of neurons in the mPFC. CORT-induced behavioural and
      dendritic morphological changes were reversible by FLX. No differences in TST
      immobility were observed between groups. On the secondary TST outcome measure,
      CORT exposure and tumor burden were associated with a trend towards decreased
      power of movement. CORT exposure induced a positive control model of a depressive
      like state, with FLX treatment confirming the predictive validity of the model.
      This verified the sensitivity of behavioural and histological tests, which were
      used to assess the CID model. The induction of a depressive-like state in this
      model represents the first successfully validated animal model of CID. 

PMID- 26222785
TI  - Socioeconomic inequalities in children's diet: the role of the home food
      environment.
AB  - BACKGROUND: It is well documented in the literature that low socioeconomic status
      (SES) is associated with lower consumption of healthy foods and that these
      differences in consumption patterns are influenced by neighborhood food
      environments. Less understood is the role that SES differences in physical and
      social aspects of the home food environment play in consumption patterns.
      METHODS: Using data on 4th grade children from the 2009-2011 Texas School
      Physical Activity and Nutrition (SPAN) study, we used mixed-effects regression
      models to test the magnitude of differences in the SPAN Health Eating Index
      (SHEI) by parental education as an indicator of SES, and the extent to which
      adjusting for measures of the home food environment, and measures of the
      neighborhood environment accounted for these SES differences. RESULTS: Small but
      significant differences in children's SHEI by SES strata exist (-1.33 between
      highest and lowest SES categories, p<0.01). However, incorporating home food
      environment and neighborhood environment measures in this model eliminates these
      differences (-0.7, p=0.145). Home food environment explains a greater portion of
      the difference. Both social (mealtime structure) and physical aspects (food
      availability) of the home food environment are strongly associated with
      consumption of healthy and unhealthy foods. CONCLUSIONS: Our findings suggest
      that modifiable parent behaviors at home can improve children's eating habits and
      that the neighborhood may impact diet in ways other than through access to
      healthy food.

PMID- 26222787
TI  - Behavioral and neural correlates of visual emotion discrimination and empathy in
      mild cognitive impairment.
AB  - Emotional and social cognitive deficits were investigated in a group of 24
      individuals with mild cognitive impairment (MCI) and 24 healthy controls.
      Empathic and visual emotional responses were collected, analyzed and correlated
      to brain structural imaging data by means of: (i) a pictorial matching-to-sample
      task with facial and non-facial stimuli; (ii) self-reported questionnaires for
      cognitive and affective emotional components, and alexithymia; (iii) in-depth
      assessment of cognitive functions. Results indicated that visual processing of
      faces in MCI individuals did not benefit from fearful emotional content which in
      healthy controls facilitates stimulus' recognition (emotional enhancement
      effect). This implicit visuo-emotional disorder was specific for the faces, did
      not generalize to other categories, and did not correlate to explicit measures of
      empathy. Thus, our main finding indicates that in MCI individuals, deficits in
      visual recognition of facial emotions may arise already in the earliest stages of
      memorization, during the visual encoding of facial emotions. Voxel-based
      morphometry revealed its association with atrophy in frontal and occipito
      temporal regions, mostly involving the anterior medial prefrontal cortex (P<0.05,
      multiple-comparison correction). Neural evidences were corroborated by clinical
      scores showing significant correlation between reduction of Emotion Enhancement
      Effect and deficits in frontal/executive functions. Crucially, the disorder did
      not appear to be related to the number of impaired cognitive domains (single or
      multiple-domain MCI) but rather to the involvement of frontal brain networks and
      frontal/executive functions. This suggests that in prodromal stages of dementia,
      frontal symptoms may represent a significant signal of emotional recognition
      disorders. 

PMID- 26222788
TI  - Evaluation of blood pressure in feline night monkeys (Aotus azarae infulatus)
      under different restraint protocols.
AB  - BACKGROUND: Feline night monkeys are very susceptible to stress when handled, and
      because of that, the use of anesthetic and physical restraint methods should be
      carefully evaluated. To ensure a safer anesthesia to the animals the present
      study aimed to observe the influence of four restraint protocols in the blood
      pressure of Aotus azarae infulatus. METHODS: Blood pressure was obtained from 10
      animals subjected to restraining protocols using tiletamine and zolazepam,
      isoflurane, ketamine and midazolam, and physical restraint and results were
      evaluated to determine their effect on this exam. RESULTS: Among the restraint
      protocols tested, the anesthetic isoflurane promoted lower blood pressure values
      and no differences were observed between values measured in both arms in all
      groups. CONCLUSION: The results of our study suggest that all restraint protocols
      tested significantly alter blood pressure in this species of primates.

PMID- 26222789
TI  - Mobile DNA Elements: The Seeds of Organic Complexity on Earth.
AB  - Mobile DNA or transposable elements (TEs) are genomic sequences capable of moving
      themselves independently into different parts of the genome. Viral invasion of
      eukaryotic genomes is assumed to be the main source of TEs. Selfish transposition
      of these elements could be a serious threat to the host cell, as they can insert
      themselves into the middle of coding genes and/or induce genomic instability. In
      response, through millions of years of evolution, cells have come up with various
      mechanisms such as genomic imprinting, DNA methylation, heterochromatin
      formation, and RNA interference to deactivate them. Interestingly, these
      processes have also greatly contributed to important cellular functions involved
      in cell differentiation, development, and differential gene expression.
      Propagation of TE copies during the course of evolution have resulted in
      increasing the genome size and providing proper space and flexibility in shaping
      the genome by creating new genes and establishing essential cellular structures
      such as heterochromatin, centromere, and telomeres. Yet, these elements are
      mostly labeled for playing a role in pathogenesis of human diseases. Here, we
      attempt to introduce TEs as factors necessary for making us human rather than
      just selfish sequences or obligatory guests invading our DNA. 

PMID- 26222791
TI  - Correction: Stronger Neural Modulation by Visual Motion Intensity in Autism
      Spectrum Disorders.

PMID- 26222790
TI  - Dynamic Neuromuscular Control of the Lower Limbs in Response to Unexpected Single
      Planar versus Multi-Planar Support Perturbations in Young, Active Adults.
AB  - PURPOSE: An anterior cruciate ligament (ACL) injury involves a multi-planar
      injury mechanism. Nevertheless, unexpected multi-planar perturbations have not
      been used to screen athletes in the context of ACL injury prevention yet could
      reveal those more at risk. The objective of this study was to compare
      neuromuscular responses to multi-planar (MPP) and single-planar perturbations
      (SPP) during a stepping-down task. These results might serve as a basis for
      future implementation of external perturbations in ACL injury screening programs.
      METHODS: Thirteen young adults performed a single leg stepping-down task in eight
      conditions (four MPP and four SPP with a specified amplitude and velocity). The
      amplitudes of vastus lateralis (VL), vastus medialis (VM), hamstrings lateralis
      (HL), hamstrings medialis (HM) EMG activity, medio-lateral and anterior-posterior
      centre of mass (COM) displacements, the peak knee flexion and abduction angles
      were compared between conditions using an one-way ANOVA. Number of stepping
      responses were monitored during all conditions. RESULTS: Significantly greater
      muscle activity levels were found in response to the more challenging MPP and SPP
      compared to the less challenging conditions (p < 0.05). No differences in
      neuromuscular activity were found between the MPP conditions and their
      equivalents in the SPP. Eighteen stepping responses were monitored in the SPP
      versus nine in the MPP indicating that the overall neuromuscular control was even
      more challenged during the SPP which was supported by greater COM displacements
      in the SPP. CONCLUSION: The more intense MPP and SPP evoked different
      neuromuscular responses resulting in greater muscle activity levels compared to
      small perturbations. Based on the results of COM displacements and based on the
      amount of stepping responses, dynamic neuromuscular control of the knee joint
      appeared less challenged during the MPP. Therefore, future work should
      investigate extensively if other neuromuscular differences (i.e. co-activation
      patterns and kinetics) exist between MPP and SPP. In addition, future work should
      examine the influence on the neuromuscular control of the magnitude of the
      perturbations and the magnitude of stepping height and stepping distance.

PMID- 26222792
TI  - In-Vitro Analysis of the Effect of Constructional Parameters and Dye Class on the
      UV Protection Property of Cotton Knitted Fabrics.
AB  - Cotton knitted fabrics were manufactured with different yarn types (conventional
      ring spun yarn and torque-free ring spun yarn) with different fibre types (combed
      cotton and combed Supima cotton) and yarn fineness (Ne30 and Ne40). These fabrics
      were then dyed with three types of dye (reactive, direct and sulphur dye) with
      three dye concentrations (0.1%, 1.0% and 5.0% on-weight of fabric (owf)) in three
      colours (red, yellow and blue). This study examined the impact of constructional
      parameters and dyeing on ultraviolet (UV) protection properties of cotton knitted
      fabric. In-vitro test with spectrophotometer was used for evaluating the UV
      protection property of dyed cotton knitted fabrics. Among the six parameters
      investigated, fineness of yarn and dye concentration were the most significant
      factors affecting UPF while the color effect is the least significant.
      Experimental results revealed that the UPF value of dyed fabrics made from combed
      cotton is generally higher than the combed Supima cotton since combed cotton is
      composed of shorter fibres which facilitate the blocking or absorption of UV
      radiation. Second, fabrics made with twist yarn (i.e. ring spun yarn) have higher
      UPF value than the corresponding ESTex one (i.e. torque-free yarn) in general
      since fabrics made with ring spun yarn tend to shrink during wet processing and
      so it is more compact. Third, the UPF value of fabrics made with 30Ne yarn was
      higher than the 40Ne one since it is thicker and has lower fabric porosity.
      Fourth, fabrics dyed with lower concentration of dye gave the lowest UPF. Fifth,
      the sulphur dyed samples performed worse than the reactive and direct dyed
      samples in terms of UV protection property. Sixth, there is no significant
      difference in UPF for red, yellow and blue coloured fabrics. Seventh, this study
      also demonstrated that lightness of fabric is negatively related to UV protection
      property. 

PMID- 26222793
TI  - Somatostatin Improved B Cells Mature in Macaques during Intestinal Ischemia
      Reperfusion.
AB  - AIMS: Intestinal ischemia-reperfusion has been taken as an important
      pathophysiological process for multiple organ dysfunctions in critical patients.
      Recent studies reported that dual expression programs of the B cells receptors
      and Toll-like receptors on B-lymphocytes permit these ubiquitous cells to
      integrate both adaptive and innate immune functions. Our previous studies found
      that somatostatin inhibited the intestinal inflammatory injury after ischemia
      reperfusion in macaques. However, the changes of B cells and the effects of
      somatostatin on B cells after intestinal ischemia-reperfusion were unclear.
      METHODS: 15 macaques were divided into control, intestinal ischemia-reperfusion
      and somatostatin pretreatment groups. Immunohistochemistry was performed to
      identify the distributions of adaptive and innate immunity markers in the iliac
      mucosa. Hmy2.cir B lymphoblastoid cell line was cultured in vitro study. Enzyme
      linked immunosorbent assay was used to measure IgM, IL-6 and SIgA, and the
      expressions of B cells transcription factors, PAX-5 and BLIMP-1, were detected by
      Western blotting. RESULTS: B2 lymphocytes in normal Peyer's patches were
      presented the phenotype of PAX-5+CD20+CD5-. Ischemia-reperfusion increased the
      numbers and sizes of Peyer's patches but with PAX-5+CD20-CD5- B cells, an
      unmatured set of B cells. Somatostatin partly kept the phenotype of mature B
      cells during ischemia-reperfusion. The innate immunity of B cells was inhibited
      whereas the adaptive immunity was increased in the intestinal mucosa in the
      somatostatin group, compared to the ischemia-reperfusion group. In vitro,
      somatostatin significantly inhibited IL-6 and promoted IgM by increasing the
      expression of both PAX-5 and BLIMP-1 in the proinflammatory condition.
      CONCLUSION: Intestinal ischemia-reperfusion resulted in the proliferation of
      unmatured B cells which were involved in the augmentation of innate immunity.
      Somatostatin, with a bi-directional regulation function on innate as well as
      adaptive immunity of B cells, greatly improved B cells mature in macaques during
      ischemia-reperfusion. Preventive supplements of somatostatin may greatly limit
      intestinal injury and bacterial translocation during ischemia-reperfusion.

PMID- 26222795
TI  - Correction: Enrichment and Analysis of Intact Phosphoproteins in Arabidopsis
      Seedlings.

PMID- 26222794
TI  - Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture.
AB  - Parrot bornavirus 4 is an etiological agent of proventricular dilatation disease,
      a fatal neurologic and gastrointestinal disease of psittacines and other birds.
      We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral
      activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4
      replication in duck embryonic fibroblast cells. Two analytical methods that
      evaluate different products of viral replication, indirect immunocytochemistry
      for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein
      gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 MUg/mL
      inhibited parrot bornavirus 4 replication, decreasing viral mRNA and viral
      protein load, in infected duck embryonic fibroblast cells. The addition of
      guanosine diminished the antiviral activity of ribavirin suggesting that one
      possible mechanism of action against parrot bornavirus 4 may likely be through
      inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot
      bornavirus 4 susceptibility to ribavirin in cell culture. 

PMID- 26222796
TI  - Suicide and Social Processes.

PMID- 26222797
TI  - Concerted Protein and Nucleic Acid Conformational Changes Observed Prior to
      Nucleotide Incorporation in a Bacterial RNA Polymerase: Raman Crystallographic
      Evidence.
AB  - Transcription elongation requires the continuous incorporation of ribonucleotide
      triphosphates into a growing transcript. RNA polymerases (RNAPs) are able to
      processively synthesize a growing RNA chain via translocation of the RNAP enzyme
      along its nucleic acid template strand after each nucleotide addition cycle. In
      this work, a time-resolved Raman spectroscopic analysis of nucleotide addition in
      single crystals of the Thermus thermophilus elongation complex (TthEC) is
      reported. When [(13)C,(15)N]GTP (*GTP) is soaked into crystals of the TthEC,
      large reversible changes in the Raman spectrum that are assigned to protein and
      nucleic acid conformational events during a single-nucleotide incorporation are
      observed. The *GTP population in the TthEC crystal reaches a stable population at
      37 min, while substantial and reversible protein conformational changes (mainly
      ascribed to changes in alpha-helical Raman features) maximize at approximately 50
      min. At the same time, changes in nucleic acid bases and phosphodiester backbone
      Raman marker bands occur. Catalysis begins at approximately 65-70 min, soon after
      the maximal protein and DNA changes, and is monitored via the decline in a
      triphosphate vibrational Raman mode from *GTP. The Raman data indicate that
      approximately 40% of the total triphosphate population, present as *GTP, reacts
      in the crystal. This may suggest that a second population of noncovalently bound
      *GTP resides in a site distinct from the catalytic site. The data reported here
      are an extension of our recent work on the elongation complex (EC) of a bacterial
      RNAP, Thermus thermophilus (Tth), where Raman spectroscopy and polyacrylamide gel
      electrophoresis were employed to monitor incorporation and misincorporation in
      single TthEC crystals [Antonopoulos, I. H., et al. (2015) Biochemistry 54, 652
      665]. Therefore, the initial study establishes the groundwork for this study. In
      contrast to our previous study, in which incorporation takes place very rapidly
      inside the crystals, the data on this single crystal exhibit a slower time
      regime, which allows the dissection of the structural dynamics associated with
      GMP incorporation within the TthEC crystal. 

PMID- 26222798
TI  - Hypomanic Episode Associated with Steroid Eye Drops in an Adolescent.

PMID- 26222799
TI  - Luminescence properties of Eu-complex formations into ordered mesoporous silica
      particles obtained by the spray pyrolysis process.
AB  - Ordered mesoporous, highly luminescent SiO2 particles have been synthesized by
      spray pyrolysis from solutions containing tetraethylorthosilicate (TEOS),
      Eu(NO3)3.6H2O, and cetyltrimethylammonium bromide (CTAB) as structure-directing
      agents. The 1,10-phenantroline (Phen) molecules were coordinated in a post
      synthesis step by a simple wet impregnation method. In addition, other matrices
      were also prepared by the encapsulation of europium complex Eu(fod)3 (where fod =
      6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) into mesoporous silica,
      and then the Phen molecules were encapsulated by different impregnation steps,
      after which the luminescence properties were investigated. The obtained materials
      were characterized by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), powder x-ray diffraction (XRD) and Fourier transform infrared
      (FTIR) spectroscopy. Powders with polydisperse spherical grains were obtained,
      displaying an ordered hexagonal array of mesochannels. Luminescence results
      revealed that Phen molecules had been successfully coordinated as an additional
      ligand in the Eu(fod)3 complex into the channels of the mesoporous particles
      without disrupting the structure. 

PMID- 26222800
TI  - Uniform Concave Polystyrene-Carbon Core-Shell Nanospheres by a Swelling Induced
      Buckling Process.
AB  - We have developed a facile procedure that can create asymmetrical building blocks
      by uniformly deforming nanospheres into C(infinityv) symmetry at low cost and
      high quality. Concave polystyrene@carbon (PS@C) core-shell nanospheres were
      produced by a very simple microwave-assisted alcohol thermal treatment of
      spherical PS@C nanoparticles. The dimensions and ratio of the concave part can be
      precisely controlled by temperature and solvents. The concavity is created by
      varying the alcohol-thermal treatment to tune the swelling properties that lead
      to the mechanical deformation of the PS@C core-shell structure. The driving force
      is attributed to the significant volume increase that occurs upon polystyrene
      core swelling with the incorporation of solvent. We propose a mechanism adapted
      from published models for the depression of soft capsules. An extrapolation from
      this model predicts that the rigid shell is used to generate a cavity in the
      unbuckled shell, which is experimentally confirmed. This swelling and deformation
      route is flexible and should be applicable to other polymeric nanoparticles to
      produce asymmetrical nanoparticles.

PMID- 26222801
TI  - Valle Agricola lentil, an unknown lentil (Lens culinaris Medik.) seed from
      Southern Italy as a novel antioxidant and prebiotic source.
AB  - In order to promote 'Valle Agricola' lentil, an autochthonous lentil of the
      Campania Region, a thorough investigation of its biochemical and nutritional
      properties has been carried out. The macronutrient content (proteins,
      carbohydrates and lipids), free and total amino acids, and unsaturated fatty
      acids were determined. The antioxidant capability of raw 'Valle Agricola'
      lentils, as well as of boiled ones, was estimated in terms of their total phenol
      content (TPC), ORAC value, and free radical scavenging capacities using DPPH and
      ABTS assays. The data obtained evidenced that the boiling process slightly
      decreased Valle Agricola lentil's antioxidant power. Furthermore, when trypsin
      and chymotrypsin inhibitory activities were measured, a large decrease of the
      levels of anti-nutritional factors was estimated. In order to have a
      phytochemical overview of this autochthonous lentil seed, LC-ESI-MS/MS analysis
      was applied to raw and boiled lentil extracts. Flavonol glycosides and free
      flavanols, as well as typical seed prebiotic saccharides, were the most
      representative constituents. 

PMID- 26222802
TI  - Aggregation of inorganic nanoparticles mediated by biomimetic oligomers.
AB  - Assemblies of nanoparticles (NPs) have been broadly used for the construction of
      materials with unique spectroscopic and chiral properties for applications in
      various scientific disciplines such as sensing, bio-nanotechnology and medicine.
      Mediating the aggregation of NPs by synthetic biomimetic oligomers, namely, DNA,
      PNA, peptides and peptide mimics, rather than by small organic molecules has been
      shown to produce interesting supramolecular structures and enable the combination
      of the biocompatibility of the mediators and the spectroscopic properties of the
      NPs. Yet, the key to using this powerful approach for designing new functional
      materials is to understand the NPs aggregation patterns induced by biopolymers
      and biomimetic oligomers. Herein we describe the important developments in this
      field, from early studies to recent work with an emphasis on synthetic methods
      and tools for controlled assembly of metal NPs by biomimetic polymers and
      oligomers. 

PMID- 26222809
TI  - Associations between multiple health risk behaviors and mental health among
      Chinese college students.
AB  - Although there is substantial evidence that health risk behaviors increase risks
      of premature morbidity and mortality, little is known about the multiple health
      risk behaviors in Chinese college students. Here, we investigated the prevalence
      of multiple health risk behaviors and its relation to mental health among Chinese
      college students. A cross-sectional study was conducted in Wuhan, China from May
      to June 2012. The students reported their health risk behaviors using self
      administered questionnaires. Depression and anxiety were assessed using the self
      rating depression scale and self-rating anxiety scale, respectively. A total of
      2422 college students (1433 males) aged 19.7 +/- 1.2 years were participated in
      the study. The prevalence of physical inactivity, sleep disturbance, poor dietary
      behavior, Internet addiction disorder (IAD), frequent alcohol use and current
      smoking was 62.0, 42.6, 29.8, 22.3, 11.6 and 9.3%, respectively. Significantly
      increased risks for depression and anxiety were found among students with
      frequent alcohol use, sleep disturbance, poor dietary behavior and IAD. Two-step
      cluster analysis identified two different clusters. Participants in the cluster
      with more unhealthy behaviors showed significantly increased risk for depression
      (odds ratio (OR): 2.21; 95% confidence interval (CI): 1.83, 2.67) and anxiety
      (OR: 2.32; 95% CI: 1.85, 2.92). This study indicates that a relatively high
      prevalence of multiple health risk behaviors was found among Chinese college
      students. Furthermore, the clustering of health risk behaviors was significantly
      associated with increased risks for depression and anxiety.

PMID- 26222810
TI  - On listening to the dreams of children affected by a serious physical illness.

PMID- 26222811
TI  - The body talks. Psychosomatic disorders during the developmental years.

PMID- 26222812
TI  - Air-Stable and Efficient PbSe Quantum-Dot Solar Cells Based upon ZnSe to PbSe
      Cation-Exchanged Quantum Dots.
AB  - We developed a single step, cation-exchange reaction that produces air-stable
      PbSe quantum dots (QDs) from ZnSe QDs and PbX2 (X = Cl, Br, or I) precursors. The
      resulting PbSe QDs are terminated with halide anions and contain residual Zn
      cations. We characterized the PbSe QDs using UV-vis-NIR absorption,
      photoluminescence quantum yield spectroscopy, X-ray diffraction, X-ray
      photoelectron spectroscopy, and transmission electron microscopy. Solar cells
      fabricated from these PbSe QDs obtained an overall best power conversion
      efficiency of 6.47% at one sun illumination. The solar cell performance without
      encapsulation remains unchanged for over 50 days in ambient conditions; and after
      50 days, the National Renewable Energy Laboratory certification team certified
      the device at 5.9%. 

PMID- 26222814
TI  - Within-breath respiratory impedance and airway obstruction in patients with
      chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Recent work has suggested that within-breath respiratory impedance
      measurements performed using the forced oscillation technique may help to
      noninvasively evaluate respiratory mechanics. We investigated the influence of
      airway obstruction on the within-breath forced oscillation technique in smokers
      and chronic obstructive pulmonary disease patients and evaluated the contribution
      of this analysis to the diagnosis of chronic obstructive pulmonary disease.
      METHODS: Twenty healthy individuals and 20 smokers were assessed. The study also
      included 74 patients with stable chronic obstructive pulmonary disease. We
      evaluated the mean respiratory impedance (Zm) as well as values for the
      inspiration (Zi) and expiration cycles (Ze) at the beginning of inspiration (Zbi)
      and expiration (Zbe), respectively. The peak-to-peak impedance (Zpp=Zbe-Zbi) and
      the respiratory cycle dependence (DeltaZrs=Ze-Zi) were also analyzed. The
      diagnostic utility was evaluated by investigating the sensitivity, the
      specificity and the area under the receiver operating characteristic curve.
      ClinicalTrials.gov: NCT01888705. RESULTS: Airway obstruction increased the within
      breath respiratory impedance parameters that were significantly correlated with
      the spirometric indices of airway obstruction (R=-0.65, p<0.0001). In contrast to
      the control subjects and the smokers, the chronic obstructive pulmonary disease
      patients presented significant expiratory-inspiratory differences (p<0.002). The
      adverse effects of moderate airway obstruction were detected based on the Zpp
      with an accuracy of 83%. Additionally, abnormal effects in severe and very severe
      patients were detected based on the Zm, Zi, Ze, Zbe, Zpp and DeltaZrs with a high
      degree of accuracy (>90%). CONCLUSIONS: We conclude the following: (1) chronic
      obstructive pulmonary disease introduces higher respiratory cycle dependence, (2)
      this increase is proportional to airway obstruction, and (3) the within-breath
      forced oscillation technique may provide novel parameters that facilitate the
      diagnosis of respiratory abnormalities in chronic obstructive pulmonary disease.

PMID- 26222815
TI  - Surgical treatment of endometrial cancer in developing countries: reasons to
      consider systematic two-step surgical treatment.
AB  - OBJECTIVE: The aim of this study was to determine the lymph node status in a
      large cohort of women with endometrial cancer from the public health system who
      were referred to an oncology reference center in Brazil to identify candidates
      for the omission of lymphadenectomy based on clinicopathological parameters.
      METHODS: We retrospectively analyzed a cohort of 310 women with endometrial
      cancer (255 endometrioid, 40 serous, and 15 clear cell tumors) treated between
      2009 and 2014. We evaluated the histological type, grade (low vs. high), tumor
      size (cm), depth of myometrial invasion (<=50%, >50%) and lymphovascular space
      invasion to determine which factors were correlated with the presence of lymph
      node metastasis. RESULTS: The factors related to lymph node involvement were
      tumor size (p=0.03), myometrial invasion (p<0.01), tumor grade (p<0.01), and
      lymphovascular space invasion (p<0.01). The histological type was not associated
      with the nodal status (p=0.52). Only twelve of 176 patients (6.8%) had low-grade
      endometrioid carcinoma, tumor size <=2 cm and <50% myometrial infiltration.
      CONCLUSIONS: The omission of lymphadenectomy based on the histological type,
      grade, tumor size and depth of myometrial invasion is not likely to have a large
      impact on the surgical treatment of endometrial cancer in our population because
      most patients present with large and advanced tumors. New strategies are proposed
      that prioritize hysterectomy performed in a general hospital as soon as possible
      after diagnosis, followed by an evaluation of the need for lymph node dissection
      at a reference center.

PMID- 26222816
TI  - Pfannenstiel incision for intact specimen extraction in laparoscopic
      transperitoneal radical nephrectomy: a longitudinal prospective outcome study.
AB  - OBJECTIVES: To evaluate the intra- and postoperative outcomes of patients
      undergoing laparoscopic radical nephrectomy with intact specimen extraction
      through a Pfannenstiel transverse suprapubic incision. METHODS: Prospective
      follow-up of 26 laparoscopic transperitoneal radical nephrectomies for suspected
      renal tumors in which the kidneys were extracted via a Pfannenstiel lower
      abdominal transverse incision. RESULTS: The mean operating time was 152.3 (80
      255) minutes, and the mean blood loss was 90 (20-300) ml. The mean extraction
      time was 20.4 (12-35) minutes. The mean weight of the removed specimen was 631.5
      (190-1505) grams, and the mean longest diameter of the extracted specimen was
      17.4 (9-25) cm. The mean extraction incision size was 10.7 (7-16) cm. No open
      surgical conversions were necessary. Pain control was excellent, with minimal
      intravenous morphine equivalent narcotic use by patients: 15.7 (0-31) mg in the
      recovery room, 33.8 (0-127) mg on the first postoperative day and 8.7 (0-60) mg
      in the first week after discharge. The patients experienced a short duration to
      full ambulation and normal dietary intake. Postoperative follow-up visits were
      recorded for at least six months. The patients reported a high cosmetic
      satisfaction rate of 97.7% (60-100). No late postoperative complications were
      observed related to the extraction site. CONCLUSIONS: The operative specimen can
      be extracted via a low transverse Pfannenstiel incision during radical
      laparoscopic nephrectomy. This incision ensures the extraction of large specimens
      while preserving the aesthetic and functional advantages of laparoscopy without
      increasing the cancer risk. The absence of muscle cutting maintains the integrity
      of the abdominal wall and elicits minimal pain. No postoperative incisional
      hernias or keloid formations were observed.

PMID- 26222817
TI  - Mean platelet volume is associated with disease severity in patients with
      obstructive sleep apnea syndrome.
AB  - OBJECTIVE: Obstructive sleep apnea syndrome is associated with cardiovascular
      diseases and thromboembolic events. The mean platelet volume (MPV) is a predictor
      of cardiovascular thromboembolic events. The aim of the present study is to
      investigate the association between the MPV and disease severity in patients with
      obstructive sleep apnea syndrome. METHODS: We prospectively included 194
      obstructive sleep apnea syndrome patients without cardiovascular disease (mean
      age 56.5+/-12.5 years) who were undergoing sleep tests. An overnight full
      laboratory polisomnography examination was conducted on each patient. The
      patients were divided into 3 groups according to the apnea-hypopnea index (AHI):
      (1) AHIlow group: 5<=AHI<15, (2) AHImid group: 15<AHI<=30, and (3) AHIhigh group:
      AHI>30. RESULTS: The highest MPV values were found in the AHIhigh group compared
      with other groups (p<0.05 for all). Multiple linear regression analysis indicated
      that the MPV was associated with the AHI (beta=0.500, p<0.001) and the high
      sensitivity C-reactive protein (hs-CRP) level (beta=0.194, p=0.010). CONCLUSION:
      The MPV is independently associated with both disease severity and inflammation
      in patients with obstructive sleep apnea syndrome.

PMID- 26222818
TI  - Liver lobe-based magnetic resonance diffusion-weighted imaging using multiple b
      values in patients with hepatitis B-related liver cirrhosis: association with the
      liver disease severity according to the Child-Pugh class.
AB  - OBJECTIVE: To determine the associations of liver lobe-based magnetic resonance
      diffusion-weighted imaging findings using multiple b values with the presence and
      Child-Pugh class of cirrhosis in patients with hepatitis B. METHODS: Seventy-four
      cirrhotic patients with hepatitis B and 25 healthy volunteers underwent diffusion
      weighted imaging using b values of 0, 500, 800 and 1000 sec/mm2. The apparent
      diffusion coefficients of individual liver lobes for b(0,500), b(0,800) and
      b(0,1000) were derived from the signal intensity averaged across images obtained
      using b values of 0 and 500 sec/mm2, 0 and 800 sec/mm2, or 0 and 1000 sec/mm2,
      respectively, and were statistically analyzed to evaluate cirrhosis. RESULTS: The
      apparent diffusion coefficients for b(0,500), b(0,800) and b(0,1000) inversely
      correlated with the Child-Pugh class in the left lateral liver lobe, the left
      medial liver lobe, the right liver lobe and the caudate lobe (r=-0.35 to -0.60,
      all p<0.05), except for the apparent diffusion coefficient for b(0,1000) in the
      left medial liver lobe (r=-0.17, p>0.05). Among these parameters, the apparent
      diffusion coefficient for b(0,500) in the left lateral liver lobe best
      differentiated normal from cirrhotic liver, with an area under the receiver
      operating characteristic curve of 0.989. The apparent diffusion coefficient for
      b(0,800) in the right liver lobe best distinguished Child-Pugh class A from B-C
      and A-B from C, with areas under the receiver operating characteristic curve of
      0.732 and 0.747, respectively. CONCLUSION: Liver lobe-based apparent diffusion
      coefficients for b(0,500) and b(0,800) appear to be associated with the presence
      and Child-Pugh class of liver cirrhosis.

PMID- 26222819
TI  - Artificial disc and vertebra system: a novel motion preservation device for
      cervical spinal disease after vertebral corpectomy.
AB  - OBJECTIVE: To determine the range of motion and stability of the human cadaveric
      cervical spine after the implantation of a novel artificial disc and vertebra
      system by comparing an intact group and a fusion group. METHODS: Biomechanical
      tests were conducted on 18 human cadaveric cervical specimens. The range of
      motion and the stability index range of motion were measured to study the
      function and stability of the artificial disc and vertebra system of the intact
      group compared with the fusion group. RESULTS: In all cases, the artificial disc
      and vertebra system maintained intervertebral motion and reestablished vertebral
      height at the operative level. After its implantation, there was no significant
      difference in the range of motion (ROM) of C(3-7) in all directions in the non
      fusion group compared with the intact group (p>0.05), but significant differences
      were detected in flexion, extension and axial rotation compared with the fusion
      group (p<0.05). The ROM of adjacent segments (C(3-4), C(6-7)) of the non-fusion
      group decreased significantly in some directions compared with the fusion group
      (p<0.05). Significant differences in the C(4-6) ROM in some directions were
      detected between the non-fusion group and the intact group. In the fusion group,
      the C(4-6) ROM in all directions decreased significantly compared with the intact
      and non-fusion groups (p<0.01). The stability index ROM (SI-ROM) of some
      directions was negative in the non-fusion group, and a significant difference in
      SI-ROM was only found in the C(4-6) segment of the non-fusion group compared with
      the fusion group. CONCLUSION: An artificial disc and vertebra system could
      restore vertebral height and preserve the dynamic function of the surgical area
      and could theoretically reduce the risk of adjacent segment degeneration compared
      with the anterior fusion procedure. However, our results should be considered
      with caution because of the low power of the study. The use of a larger sample
      should be considered in future studies.

PMID- 26222820
TI  - Olmesartan restores the protective effect of remote ischemic perconditioning
      against myocardial ischemia/reperfusion injury in spontaneously hypertensive
      rats.
AB  - OBJECTIVES: Remote ischemic perconditioning is the newest technique used to
      lessen ischemia/reperfusion injury. However, its effect in hypertensive animals
      has not been investigated. This study aimed to examine the effect of remote
      ischemic perconditioning in spontaneously hypertensive rats and determine whether
      chronic treatment with Olmesartan could influence the effect of remote ischemic
      perconditioning. METHODS: Sixty rats were randomly divided into six groups:
      vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic
      perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan
      remote ischemic perconditioning. The left ventricular mass index, creatine kinase
      concentration, infarct size, arrhythmia scores, HIF-1alpha mRNA expression, miR
      21 expression and miR-210 expression were measured. RESULTS: Olmesartan
      significantly reduced the left ventricular mass index, decreased the creatine
      kinase concentration, limited the infarct size and reduced the arrhythmia score.
      The infarct size, creatine kinase concentration and arrhythmia score during
      reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle
      remote ischemic perconditioning group. However, these values were significantly
      decreased in the olmesartan-remote ischemic perconditioning group compared to the
      olmesartan-ischemia/reperfusion injury group. HIF-1alpha, miR-21 and miR-210
      expression were markedly down-regulated in the Olmesartan-sham group compared to
      the vehicle-sham group and significantly up-regulated in the olmesartan-remote
      ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion
      injury group. CONCLUSION: The results indicate that (1) the protective effect of
      remote ischemic perconditioning is lost in vehicle-treated rats and that chronic
      treatment with Olmesartan restores the protective effect of remote ischemic
      perconditioning; (2) chronic treatment with Olmesartan down-regulates HIF-1alpha,
      miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting
      ischemia/reperfusion injury; and (3) recovery of the protective effect of remote
      ischemic perconditioning is related to the up-regulation of HIF-1alpha, miR-21
      and miR-210 expression.

PMID- 26222821
TI  - Effects of ethyl pyruvate on leukocyte-endothelial interactions in the mesenteric
      microcirculation during early sepsis treatment.
AB  - OBJECTIVES: Experimental studies on sepsis have demonstrated that ethyl pyruvate
      is endowed with antioxidant and anti-inflammatory properties. This study aimed to
      investigate the effects of ethyl pyruvate on leukocyte-endothelial interactions
      in the mesenteric microcirculation in a live Escherichia coli-induced sepsis
      model in rats. METHODS: Male Wistar rats were administered an intravenous
      suspension of E. coli bacteria or were subjected to a sham procedure. Three hours
      after bacterial infusion, the rats were randomized into the following groups: a
      control group without treatment, a group treated with lactated Ringer's solution
      (4 mL/kg, i.v.), and a group treated with lactated Ringer's solution (4 mL/kg,
      i.v.) plus ethyl pyruvate (50 mg/kg). At 24 h after bacterial infusion, leukocyte
      endothelial interactions were investigated using intravital microscopy, and the
      expression of P-selectin and intercellular adhesion molecule-1 was evaluated via
      immunohistochemistry. White blood cell and platelet counts were also determined
      at baseline and 3 h and 24 h after E. coli inoculation. RESULTS: The non-treated
      and lactated Ringer's solution-treated groups exhibited increases in the numbers
      of rolling leukocytes (~2.5-fold increase), adherent cells (~3.0-fold), and
      migrated cells (~3.5-fold) compared with the sham group. In contrast, treatment
      with Ringer's ethyl pyruvate solution reduced the numbers of rolling, adherent
      and migrated leukocytes to the levels observed in the sham group. Additionally,
      the expression of P-selectin and intercellular adhesion molecule-1 was
      significantly increased on mesenteric microvessels in the non-treated group
      compared with the sham group (p<0.001). The expression of both adhesion molecules
      was reduced in the other groups, with ethyl pyruvate being more effective than
      lactated Ringer's solution. Infusion of bacteria caused significant leukopenia (3
      h), followed by leukocytosis with granulocytosis (24 h). There was also an
      intense and progressive reduction in the number of platelets. However, no
      differences were observed after treatment with the different solutions.
      CONCLUSIONS: The presented data suggest that ethyl pyruvate efficiently reduces
      the inflammatory response in the mesenteric microcirculation in an experimental
      model of sepsis induced by live E. coli and is associated, at least in part, with
      down-regulation of P-selectin and intercellular adhesion molecule-1.

PMID- 26222822
TI  - Cytomegalovirus infection in transplant recipients.
AB  - Cytomegalovirus infection is a frequent complication after transplantation. This
      infection occurs due to transmission from the transplanted organ, due to
      reactivation of latent infection, or after a primary infection in seronegative
      patients and can be defined as follows: latent infection, active infection, viral
      syndrome or invasive disease. This condition occurs mainly between 30 and 90 days
      after transplantation. In hematopoietic stem cell transplantation in particular,
      infection usually occurs within the first 30 days after transplantation and in
      the presence of graft-versus-host disease. The major risk factors are when the
      recipient is cytomegalovirus seronegative and the donor is seropositive as well
      as when lymphocyte-depleting antibodies are used. There are two methods for the
      diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase
      chain reaction. Serology has no value for the diagnosis of active disease,
      whereas histology of the affected tissue and bronchoalveolar lavage analysis are
      useful in the diagnosis of invasive disease. Cytomegalovirus disease can be
      prevented by prophylaxis (the administration of antiviral drugs to all or to a
      subgroup of patients who are at higher risk of viral replication) or by
      preemptive therapy (the early diagnosis of viral replication before development
      of the disease and prescription of antiviral treatment to prevent the appearance
      of clinical disease). The drug used is intravenous or oral ganciclovir; oral
      valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue
      for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and
      the gold-standard drug is intravenous ganciclovir. Treatment should be given for
      2 to 3 weeks and should be continued for an additional 7 days after the first
      negative result for viremia. 

PMID- 26222823
TI  - Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta
      analysis.
AB  - Recently, a series of studies explored the correlation between the neutrophil to
      lymphocyte ratio and the prognosis of lung cancer. However, the current opinion
      regarding the prognostic role of the neutrophil to lymphocyte ratio in lung
      cancer is inconsistent. We performed a meta-analysis of published articles to
      investigate the prognostic value of the neutrophil to lymphocyte ratio in lung
      cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were
      calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall
      survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; P(heterogeneity)=0.001)
      from multivariate studies and 1.867 (95%CI: 1.487-2.344; P(heterogeneity)=0.047)
      from univariate studies. Subgroup analysis showed that a high neutrophil to
      lymphocyte ratio yielded worse overall survival in non-small cell lung cancer
      (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; P(heterogeneity)=0.003) as well as small
      cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; P(heterogeneity)=0.625)
      in multivariate studies. The synthesized evidence from this meta-analysis of
      published articles demonstrated that an elevated neutrophil to lymphocyte ratio
      was a predictor of poor overall survival in patients with lung cancer.

PMID- 26222824
TI  - Ischemia-modified albumin must be evaluated as an oxidative stress marker
      together with albumin and bilirubin in individuals with acute appendicitis.

PMID- 26222825
TI  - Correction: Quality of life of adolescents with type 1 diabetes.

PMID- 26222826
TI  - Circadian Macronutrients Variations over the First 7 Weeks of Human Milk Feeding
      of Preterm Infants.
AB  - BACKGROUND: Little is known about circadian variations of macronutrients content
      of expressed preterm human milk (HM). This study evaluated diurnal variations of
      macronutrients and energy content of preterm HM over the first 7 weeks of
      lactation and tested the hypothesis that values obtained during a morning sample
      are predictive of those obtained from an evening sample. MATERIALS AND METHODS:
      Expressed HM was obtained from 32 mothers of preterm infants (26-33 weeks in
      gestational age), who routinely expressed all their milk every 3 hours from the
      beginning of the second to the seventh week after delivery. One aliquot was
      obtained from the first morning expression and the second from the evening
      expression. Energy and macronutrients contents were measured using an HM
      analyzer. RESULTS: Mean fat and energy contents of all samples obtained during
      the whole period were significantly higher in evening samples (p < 0.0001). There
      were no significant differences between morning and evening carbohydrates and
      protein contents. Concentrations of protein, carbohydrates, and fat from morning
      samples were predictive of evening concentrations to different extents (R(2) =
      0.720, R(2) = 0.663, and R(2) = 0.20, respectively; p < 0.02). The predictability
      of evening values by morning values was not influenced by the week of lactation
      at sampling or by individual patients. In repeated-measures analysis of variance
      performed on 11 patients who completed the whole 7-week period, over time, there
      was a significant decrease in fat, energy, and protein contents, whereas
      carbohydrates content remained unchanged. Day-night differences remained
      significant only for fat content. CONCLUSIONS: Circadian variations in fat and
      energy concentrations of HM are consistent over the first 7 weeks of lactation.
      There are no consistent circadian variations in HM protein and carbohydrates.
      Over a given day, there are little variations in protein and carbohydrates
      content, but fat concentrations are more variable, and evening values are less
      well predicted by morning sample analysis than values for protein or
      carbohydrates.

PMID- 26222827
TI  - Atlas-based estimation of lung and lobar anatomy in proton MRI.
AB  - PURPOSE: To propose an accurate methodological framework for automatically
      segmenting pulmonary proton MRI based on an optimal consensus of a spatially
      normalized library of annotated lung atlases. METHODS: A library of 62 manually
      annotated lung atlases comprising 48 mixed healthy, chronic obstructive pulmonary
      disease, and asthmatic subjects of a large age range with multiple ventilation
      levels is used to produce an optimal segmentation in proton MRI, based on a
      consensus of the spatially normalized library. An extension of this methodology
      is used to provide best-guess estimates of lobar subdivisions in proton MRI from
      annotated computed tomography data. RESULTS: A leave-one-out evaluation strategy
      was used for evaluation. Jaccard overlap measures for the left and right lungs
      were used for performance comparisons relative to the current state-of-the-art
      (0.966 +/- 0.018 and 0.970 +/- 0.016, respectively). Best-guess estimates for the
      lobes exhibited comparable performance levels (left upper: 0.882 +/- 0.059, left
      lower: 0.868 +/- 0.06, right upper: 0.852 +/- 0.067, right middle: 0.657 +/-
      0.130, right lower: 0.873 +/- 0.063). CONCLUSION: An annotated atlas library
      approach can be used to provide good lung and lobe estimation in proton MRI. The
      proposed framework is useful for subsequent anatomically based analysis of
      structural and/or functional pulmonary image data. Magn Reson Med 76:315-320,
      2016. (c) 2015 Wiley Periodicals, Inc.

PMID- 26222828
TI  - Bacterial Respiration and Growth Rates Affect the Feeding Preferences, Brood Size
      and Lifespan of Caenorhabditis elegans.
AB  - Bacteria serve as live food and nutrients for bacterial-feeding nematodes (BFNs)
      in soils, and influence nematodes behavior and physiology through their
      metabolism. Five bacterial taxa (Bacillus amyloliquefaciens JX1, Variovorax sp.
      JX14, Bacillus megaterium JX15, Pseudomonas fluorescens Y1 and Escherichia coli
      OP50) and the typical BFN Caenorhabditis elegans were selected to study the
      effects of bacterial respiration and growth rates on the feeding preferences,
      brood size and lifespan of nematodes. P. fluorescens Y1 and E. coli OP50 were
      found to be more active, with high respiration and rapid growth, whereas B.
      amyloliquefaciens JX1 and B. megaterium JX15 were inactive. The nematode C.
      elegans preferred active P. fluorescens Y1 and E. coli OP50 obviously.
      Furthermore, worms that fed on these two active bacteria produced more offspring
      but had shorter lifespan, while inactive and less preferred bacteria had
      increased nematodes lifespan and decreased the brood size. Based on these
      results, we propose that the bacterial activity may influence the behavior and
      life traits of C. elegans in the following ways: (1) active bacteria reproduce
      rapidly and emit high levels of CO2 attracting C. elegans; (2) these active
      bacteria use more resources in the nematodes' gut to sustain their survival and
      reproduction, thereby reducing the worm's lifespan; (3) inactive bacteria may
      provide less food for worms than active bacteria, thus increasing nematodes
      lifespan but decreasing their fertility. Nematodes generally require a balance
      between their preferred foods and beneficial foods, only preferred food may not
      be beneficial for nematodes. 

PMID- 26222829
TI  - Growth Factors Cross-Linked to Collagen Microcarriers Promote Expansion and
      Chondrogenic Differentiation of Human Mesenchymal Stem Cells.
AB  - Tissue engineering is a field in progressive expansion and requires constant
      updates in methods and devices. One of the central fields is the development of
      biocompatible, biodegradable, and injectable scaffolds, such as collagen
      microcarriers. To enhance cell attachment and produce a cost-effective cell
      culture solution with local stimulation of cells, basic fibroblast growth factor
      (bFGF) or transforming growth factor-beta1 (TGF-beta1) was covalently immobilized
      on microcarriers either by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N
      hydroxysuccinimide (EDC/NHS) or riboflavin/UV (RB/UV) light-mediated cross
      linking. Collagen microcarriers cross-linked with bFGF or TGF-beta1 were used for
      expansion and chondrogenic differentiation of human mesenchymal stem cells
      (MSCs). Evaluation methods included cell viability test, chondrogenic marker
      expression (aggrecan and collagen type I and type II), histological detection of
      proteoglycans, and immunohistochemical analysis. Cross-linking strengthened the
      collagen structure of the microcarriers and reduced collagenase-mediated
      degradation. MSCs effectively proliferated on microcarriers cross-linked with
      bFGF, especially by EDC/NHS cross-linking. Chondrogenic differentiation of MSCs
      was induced by TGF-beta1 cross-linked on microcarriers, promoting gene expression
      and protein accumulation of aggrecan and collagen type I and type II, as well as
      proteoglycans. Cross-linking by RB/UV enhanced chondrogenesis more than any other
      group. In addition, cross-linking reduced scaffold shrinkage exerted by MSCs
      during chondrogenesis, a desirable feature for microcarriers if used as tissue
      defect filler. In conclusion, cross-linking of bFGF or TGF-beta1 to collagen
      microcarriers supported in vitro proliferation and chondrogenesis, respectively.
      If translated in vivo and in clinical practice, such approach might lead a step
      closer to development of a cost-effective and locally acting device for cell
      based therapy. 

PMID- 26222831
TI  - New Insights on the Reaction Pathway Leading to Lactyl-ThDP: A Theoretical
      Approach.
AB  - In all ThDP-dependent enzymes, the catalytic cycle is initiated with the attack
      of the C2 atom of the ylide intermediate on the Calpha atom of a pyruvate
      molecule to form the lactyl-ThDP (L-ThDP) intermediate. In this study, the
      reaction between the ylide intermediate and pyruvate leading to the formation of
      L-ThDP is addressed from a theoretical point of view. The study includes
      molecular dynamics, exploration of the potential energy surface by means of QM/MM
      calculations, and reactivity analysis on key centers. The results show that the
      reaction occurs via a concerted mechanism in which the carboligation and the
      proton transfers occur synchronically. It is also observed that during the
      reaction the protonation state of the N1' atom changes: the reaction starts with
      the ylide having the N1' atom deprotonated and reaches a transition state showing
      the N1' atom protonated. This conversion leads to the reaction path of minimum
      energy, with an activation energy of about 20 kcal mol(-1). On the other hand, it
      is also observed that the approaching distance between the pyruvate and the
      ylide, i.e., the Calpha-C2 distance, plays a fundamental role in the reaction
      mechanism since it determines the nucleophilic character of key atoms of the
      ylide, which in turn trigger the elemental reactions of the mechanism. 

PMID- 26222830
TI  - Arabidopsis Raf-Like Mitogen-Activated Protein Kinase Kinase Kinase Gene Raf43 Is
      Required for Tolerance to Multiple Abiotic Stresses.
AB  - Mitogen-activated protein kinase (MAPK) cascades are critical signaling modules
      that mediate the transduction of extracellular stimuli into intracellular
      response. A relatively large number of MAPKKKs have been identified in a variety
      of plant genomes but only a few of them have been studied for their biological
      function. In the present study, we identified an Arabidopsis Raf-like MAPKKK gene
      Raf43 and studied its function in biotic and abiotic stress response using a T
      DNA insertion mutant raf43-1 and two Raf43-overexpressing lines Raf43-OE#1 and
      Raf43-OE#13. Expression of Raf43 was induced by multiple abiotic and biotic
      stresses including treatments with drought, mannitol and oxidative stress or
      defense signaling molecule salicylic acid and infection with necrotrophic fungal
      pathogen Botrytis cinerea. Seed germination and seedling root growth of raf43-1
      were significantly inhibited on MS medium containing mannitol, NaCl, H2O2 or
      methyl viologen (MV) while seed germination and seedling root growth of the Raf43
      OE#1 and Raf43-OE#13 lines was similar to wild type Col-0 under the above stress
      conditions. Soil-grown raf43-1 plants exhibited reduced tolerance to MV, drought
      and salt stress. Abscisic acid inhibited significantly seed germination and
      seedling root growth of the raf43-1 line but had no effect on the two Raf43
      overexpressing lines. Expression of stress-responsive RD17 and DREB2A genes was
      significantly down-regulated in raf43-1 plants. However, the raf43-1 and Raf43
      overexpressing plants showed similar disease phenotype to the wild type plants
      after infection with B. cinerea or Pseudomonas syringae pv. tomato DC3000. Our
      results demonstrate that Raf43, encoding for a Raf-like MAPKKK, is required for
      tolerance to multiple abiotic stresses in Arabidopsis. 

PMID- 26222832
TI  - Experimental studies of microbial populations and incidence of zoonotic pathogens
      in the faeces of red deer (Cervus elaphus).
AB  - Wild animals can serve as hosts, amplifiers or reservoirs for various zoonotic
      diseases. Most species of deer in highly fragmented agricultural landscapes,
      search out maximum cover from intrusive human activity. Hence, the likelihood of
      zoonosis transmission is likely to increase the more humans and wildlife
      interact. In our study, we conducted a comparative analysis of bacteria isolated
      from the faeces of red deer (Cervus elaphus) living in their natural environment
      in south-western Poland and brought in from Hungary and Slovakia under a species
      reintroduction programme. The faecal bacterial flora from 120 specimens of deer
      were examined, with particular attention to potentially pathogenic agents. We
      isolated 458 micro-organisms, of which 13 (2.84%) were identified as EHEC
      (Enterohaemorrhagic Escherichia coli) strains, and of these one strain, produced
      the Shiga toxin. No strain was identified as having ESBL (Extended-Spectrum Beta
      Lactamase) resistance. Other bacteria that are important in terms of the health
      of humans and animals included Yersinia enterocolitica (4, 0.67%) and
      Staphylococcus aureus (4, 0.67%), but without methicillin resistance, and
      Listeria monocytogenes (8, 1.75%). Of all the micro-organisms 138 (30.13%) were
      bacteria of the genus Enterococcus, including 12 (2.62%) of the species
      Enterococcus faecium. The results of the study indicate that red deer may play an
      important role in the environmental maintenance of zoonotic pathogens.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A particularly important factor in the
      epidemiology of bacterial infections is the introduction of pathogens posing a
      risk to other animals and humans into the soil, plants and especially water, as
      contaminants together with faeces. Our study presents screening of potentially
      pathogenic bacteria in different populations of deer that were displaced under
      reintroduction programmes. Based on our own research and the literature data, it
      seems that wild ruminants play an important role in the maintenance of zoonotic
      pathogens and information about zoonoses from red deer will become increasingly
      important as deer populations continue to grow, especially in Europe.

PMID- 26222833
TI  - Surface Study of Lithium-Air Battery Oxygen Cathodes in Different Solvent
      Electrolyte pairs.
AB  - The O2/Li2O2 electrode reaction has been studied on low surface area Au
      electrodes in three solvent-electrolyte pairs (0.1 M LiPF6/DMSO, LiPF6/ACN, and
      LiBF4/ACN) using an electrochemical cell coupled to UHV XPS spectrometer, EQCM,
      AFM, and DEMS. The XPS spectra of the surfaces after treatment at selected
      electrode potentials for the O2 reduction and reoxidation of the surface show the
      presence of C and S from solvent decomposition and of F and P from electrolyte
      decomposition. Furthermore, Li 1s and O 1s peaks due to Li2O2 and decomposition
      products such as carbonate, organics, LiF, high oxidation sulfur, and phosphorus
      compounds were also observed. Using ACN instead of DMSO results in less solvent
      decomposition, whereas using LiBF4 results in less electrolyte decomposition.
      XPS, AFM, and EQCM show that O2 reduction products removal only takes place at
      very high overpotentials. In agreement with XPS which shows removal of carbonate
      surface species, DEMS confirms evolution of CO2 and consumption of O2 at 4.5 V,
      but LiF cannot be removed completely in a round trip of the Li-O2 battery
      cathode. 

PMID- 26222836
TI  - Short-range inversions: rethinking organelle genome stability: template switching
      events during DNA replication destabilize organelle genomes.
AB  - In the organelles of plants and mammals, recent evidence suggests that genomic
      instability stems in large part from template switching events taking place
      during DNA replication. Although more than one mechanism may be responsible for
      this, some similarities exist between the different proposed models. These can be
      separated into two main categories, depending on whether they involve a single
      strand-switching or a reciprocal-strand-switching event. Single-strand-switching
      events lead to intermediates containing Y junctions, whereas reciprocal-strand
      switching creates Holliday junctions. Common features in all the described models
      include replication stress, fork stalling and the presence of inverted repeats,
      but no single element appears to be required in all cases. We review the field,
      and examine the ideas that several mechanisms may take place in any given genome,
      and that the presence of palindromes or inverted repeats in certain regions may
      favor specific rearrangements. 

PMID- 26222835
TI  - Temporal changes in calcium-binding proteins in the medial geniculate nucleus of
      the monkey Sapajus apella.
AB  - The subdivisions of the medial geniculate complex can be distinguished based on
      the immunostaining of calcium-binding proteins and by the properties of the
      neurons within each subdivision. The possibility of changes in neurochemistry in
      this and other central auditory areas are important aspects to understand the
      basis that contributing to functional variations determined by environmental
      cycles or the animal's cycles of activity and rest. This study investigated, for
      the first time, day/night differences in the amounts of parvalbumin-, calretinin-
      and calbindin-containing neurons in the thalamic auditory center of a non-human
      primate, Sapajus apella. The immunoreactivity of the PV-IR, CB-IR and CR-IR
      neurons demonstrated different distribution patterns among the subdivisions of
      the medial geniculate. Moreover, a high number of CB- and CR-IR neurons were
      found during day, whereas PV-IR was predominant at night. We conclude that in
      addition to the chemical heterogeneity of the medial geniculate nucleus with
      respect to the expression of calcium-binding proteins, expression also varied
      relative to periods of light and darkness, which may be important for a possible
      functional adaptation of central auditory areas to environmental changes and thus
      ensure the survival and development of several related functions. 

PMID- 26222837
TI  - Highly Electrically Conducting Glass-Graphene Nanoplatelets Hybrid Coatings.
AB  - Hybrid coatings consisting of a heat resistant Y2O3-Al2O3-SiO2 (YAS) glass
      containing 2.3 wt % of graphene nanoplatelets (GNPs) were developed by flame
      spraying homogeneous ceramic powders-GNP granules. Around 40% of the GNPs
      survived the high spraying temperatures and were distributed along the splat
      interfaces, forming a percolated network. These YAS-GNP coatings are potentially
      interesting in thermal protection systems and electromagnetic interference
      shields for aerospace applications; therefore silicon carbide (SiC) materials at
      the forefront of those applications were employed as substrates. Whereas the YAS
      coatings are nonconductive, the YAS-GNP coatings showed in-plane electrical
      conductivity (~10(2) S.m(-1)) for which a low percolation limit (below 3.6 vol %)
      is inferred. Indentation tests revealed the formation of a highly damaged
      indentation zone showing multiple shear displacements between adjacent splats
      probably favored by the graphene sheets location. The indentation radial cracks
      typically found in brittle glass coatings are not detected in the hybrid coatings
      that are also more compliant. 

PMID- 26222838
TI  - Identifying psychosocial risk among mothers in an Australian private maternity
      setting: A pilot study.
AB  - BACKGROUND: Psychosocial assessment and depression screening are recommended for
      all pregnant and postnatal women in Australia. However, women who give birth in
      private maternity settings remain less likely to participate in psychosocial
      assessment programs, making it difficult to comment on the potential resource
      implications. AIMS: To describe the psychosocial profile of a sample of women who
      had recently given birth in a private hospital and to examine the acceptability
      and feasibility of introducing psychosocial assessment as a routine component of
      maternity care. MATERIALS AND METHODS: Two hundred and twenty participants were
      recruited in a four-month period from a private tertiary hospital located in
      Murdoch, Western Australia. All participants completed the Edinburgh Depression
      Scale (EDS) and a Antenatal Risk Questionnaire (ANRQ) prior to discharge via an
      iPad. RESULTS: The mean total score for the EDS was 4.77 (SD = 3.93), with 5% of
      women scoring above the recommended cut-off of 13 or more. The mean total score
      for the ANRQ was 17.73 (SD = 10.72). 45.0% of all women endorsed no significant
      risk factors. The proportion of women scoring above the recommended ANRQ cut-off
      of 23 or more was 32.3%. Approximately 11% of women were referred for additional
      support or treatment. Acceptability of the ANRQ was high at 97.3%. CONCLUSIONS:
      This study describes the psychosocial profile of a sample of women who recently
      gave birth in an Australian private maternity hospital and demonstrates that with
      additional resources, the implementation of psychosocial assessment as a routine
      component of maternity care was feasible and highly acceptable in this setting.

PMID- 26222839
TI  - Silver-catalysed reactions of alkynes: recent advances.
AB  - Silver is a less expensive noble metal. Superior alkynophilicity due to pi
      coordination with the carbon-carbon triple bond makes silver salts ideal
      catalysts for alkyne-based organic reactions. This review highlights the progress
      in alkyne chemistry via silver catalysis primarily over the past five years (ca.
      2010-2014). The discussion is developed in terms of the bond type formed with the
      acetylenic carbon (i.e., C-C, C-N, C-O, C-Halo, C-P and C-B). Compared with other
      coinage metals such as Au and Cu, silver catalysis is frequently observed to be
      unique. This critical review clearly indicates that silver catalysis provides a
      significant impetus to the rapid evolution of alkyne-based organic reactions,
      such as alkynylation, hydrofunctionalization, cycloaddition, cycloisomerization,
      and cascade reactions. 

PMID- 26222841
TI  - Surgical Excision of Orbital Cysticercosis Lodged in Superior Oblique Muscle:
      Clinical Case Report.
AB  - Ocular cysticercosis refers to parasitic infections in humans. Most cases were
      treated by medicine. The case we reviewed was rarely reported with successful
      surgical intervention treatment.This case report describes a patient with
      cysticercosis existing in superior oblique tendon. The main symptom of the
      patient was recurring history of painless orbital swelling and double vision in
      upgaze. Ocular motility examination revealed a restriction of the right eye in
      levoelevation. A contrast-enhanced computed tomographic scan of the orbit
      revealed the presence of a well-defined hypodense cystic lesion within the right
      superior oblique muscle.The patient was diagnosed with orbital space-occupying
      mass with acquired Brown syndrome. Surgical exploration of the superior oblique
      muscle was performed, and the cyst was removed from the eye and confirmed by
      histopathological examination. After surgery, an ocular motility examination
      revealed orthotropia in the primary position and downgaze, with mild restriction
      in levoelevation.Surgical removal could substitute for medical therapy when the
      cysticercosis is lodged in the superior oblique muscle, although, prior to
      surgery, important factors, such as patient requirements, surgical skills of the
      surgeon, and cyst placement, should be considered. 

PMID- 26222840
TI  - Anthropometric and Quality-of-Life Parameters in Acute Intermittent Porphyria
      Patients.
AB  - The porphyrias are a group of rare metabolic disorders. The incidence and
      prevalence are low because the acute intermittent porphyria (AIP) is rare. Our
      aim was to assess the use of anthropometric and quality-of-life parameters in
      porphyric patients in order to identify predictor factors that might help in
      characterizing AIP patients.Sixteen AIP patients from Murcia (Spain) were
      recruited from local health centers in 2008 and 2009. A control group of 16
      healthy people was established. Body composition was assessed by bioelectrical
      impedance analysis (BIA) and anthropometric measurements: body weight; height;
      knee-heel height; waist, hip, upper arm and calf circumferences (CCs); biacromion
      and biiliac diameters; bicondylar and biepicondylar width; and triceps,
      subscapular, supraspinale, and calf skinfold thickness. Anthropometric indicators
      were obtained from anthropometric measurements. A quality-of-life evaluation was
      carried out using the EuroQol-5D (EQ-5D) questionnaire and Barthel and Katz
      indexes. Significant differences in means were tested by unpaired Student t test.
      Group differences in anthropometric measurements were tested with a 2-way
      analysis of variance (group * condition: age group, overweight, and adiposity
      degree). Relative frequencies were obtained for noncontinuous variables.
      Significant differences in prevalence were calculated by means of chi.AIP
      patients showed statistically significant differences in terms of knee-heel
      height, biiliac diameter, CC, triceps skinfold thickness, BIA, ponderal index,
      endomorphy, and ectomorphy. Only 1 quality-of-life indicator, visual analog
      scale, in the EQ-5D questionnaire showed significant differences between
      porphyric and control groups.Some anthropometric parameters and the EQ-5D
      questionnaire could be used to appreciate the presence or follow the evolution of
      the disease in AIP patients. 

PMID- 26222842
TI  - Results of Trabectome Surgery Following Failed Glaucoma Tube Shunt Implantation:
      Cohort Study.
AB  - To evaluate the safety and efficacy of Trabectome after failed tube shunt
      surgery.Twenty patients with prior failed tube shunt surgery who underwent
      Trabectome alone were included. All patients had at least 3 months of follow-up.
      Outcomes measured included intraocular pressure (IOP), glaucoma medications, and
      secondary glaucoma surgeries. The success for Kaplan-Meier survival analysis is
      defined as IOP <=21 mm Hg, IOP reduced by at least 20% from preoperative IOP, and
      no secondary glaucoma surgery.Mean preoperative IOP was 23.7 +/- 6.4 mm Hg and
      mean number of glaucoma medications was 3.2 +/- 1.5. At 12 months, IOP was
      reduced to 15.5 +/- 3.2 mm Hg (P = 0.05) and number of medications was reduced to
      2.4 +/- 1.5 (P = 0.44). Survival rate at 12 months was 84% and 3 patients
      required additional glaucoma surgery with 15 patients reaching 12 months follow
      up. Other than failure of IOP control and transient hypotony (IOP < 3 mm Hg) day
      1 in 2 cases, there were no adverse events.Trabecular bypass procedures have
      traditionally been considered an approach appropriate for early-to-moderate
      glaucoma; however, our study indicates benefit in refractory glaucoma as well.
      Eyes that are prone to conjunctival scarring and hypertrophic wound healing, such
      as those who have failed tube shunt surgery, may benefit from procedures that
      avoid conjunctival incision such as Trabectome. This study indicates potential
      benefits in this patient population.Trabectome was safe and effective in reducing
      IOP at 1-year follow-up in patients with prior failed tube shunt surgery, but not
      effective in reducing medication reliance in these patients.

PMID- 26222843
TI  - Popliteal Artery Aneurysm Repair in the Endovascular Era: Fourteen-Years Single
      Center Experience.
AB  - To compare outcomes of popliteal artery aneurysm (PAA) repair by endovascular
      treatment, great saphenous vein (GSV) bypass, and prosthetic bypass.Single center
      retrospective analysis of patients presenting PAA from 2000 to 2013. Patients
      were divided into endovascular treatment (group A); GSV bypass (group B); and
      prosthetic graft bypass (group C). Outcomes were technical success, perioperative
      mortality, and morbidity. Survival, primary and secondary patency, and freedom
      from reintervention rate were estimated. Differences in ankle-brachial index
      (ABI), in-hospital length of stay (InH-Los), red blood cell (RBC) transfusion,
      and limb loss were reported. Mean follow-up was 49 (median: 35; 1-145; SD 42)
      months.Sixty-seven patients were included; 25 in group A, 28 in group B, and 14
      in group C. PAA was symptomatic in 23 (34%) cases. Technical success was 100%. No
      perioperative death occurred. Three (4.5%) perioperative complications were
      reported with no significant difference between groups (P = 0.866). Five-years
      estimated survival was 78%. Estimated 5-years primary patency for groups A, B,
      and C was 71%, 81%, and 69%, respectively (P = 0.19). Estimated 5-years secondary
      patency for groups A, B, and C was 88%, 85%, and 84% (P = 0.85). Estimated 5
      years freedom from reintervention for groups A, B, and C was 62%, 84%, and 70%,
      respectively (P = 0.16). A significant difference between preoperative ABI versus
      postoperative ABI was observed (P = 0.001). InH-LoS was significantly shorter in
      group A (P < 0.001). RBC transfusions were required significantly less in group A
      when compared to group C (P = 0.045). Overall limb salvage was achieved in all
      but 1 patient.PAA repair has good early and long-term outcomes with different
      treatment options. Endovascular treatment was not inferior to surgical repair
      with a reduced InH-LoS and RBC transfusion. It can be successfully employed even
      in nonelective setting. A randomized controlled trial with long-term follow-up
      and appropriate patient inclusion criteria is necessary to compare these 3
      treatment options.

PMID- 26222844
TI  - "Sudden Drop" in Blood Pressure is Associated With Recanalization After
      Thrombolysis.
AB  - We aim to investigate whether the phenomenon of "sudden drop" in blood pressure
      (BP) within the first 2 hours is associated with vessel recanalization.We
      retrospectively examined clinical and imaging data from a consecutive series of
      patients with stroke with large vessel occlusion treated with intravenous
      thrombolysis (IVT). BP was monitored every 15 minutes during the first 2 hours,
      then every 30 minutes for 6 hours, and then every hour for 16 hours.We observed
      the phenomenon of "sudden drop" in systolic BP (>=20 mm Hg) in 82 (50.9%)
      patients in the first 2 hours and vessel recanalization in 87 (54.0%) patients 24
      hours after treatment. This phenomenon was independently associated with
      recanalization (odds ratio 2.100; 95% confidence interval: 1.085-4.062; P =
      0.028) after adjusting for the history of atrial fibrillation, coronary heart
      disease, and hypertension.The phenomenon of "sudden drop" in systolic BP with 20
      mm Hg or greater between 2 continuous measurements within the first 2 hours is
      associated with recanalization after IVT in patients with large vessel occlusion,
      especially for middle cerebral artery occlusion.

PMID- 26222845
TI  - Prognostic Role of Hypothyroidism in Heart Failure: A Meta-Analysis.
AB  - Hypothyroidism is a risk factor of heart failure (HF) in the general population.
      However, the relationship between hypothyroidism and clinical outcomes in
      patients with established HF is still inconclusive.We conducted a systematic
      review and meta-analysis to clarify the association of hypothyroidism and all
      cause mortality as well as cardiac death and/or hospitalization in patients with
      HF. We searched MEDLINE via PubMed, EMBASE, and Scopus databases for studies of
      hypothyroidism and clinical outcomes in patients with HF published up to the end
      of January 2015. Random-effects models were used to estimate summary relative
      risk (RR) statistics. We included 13 articles that reported RR estimates and 95%
      confidence intervals (95% CIs) for hypothyroidism with outcomes in patients with
      HF. For the association of hypothyroidism with all-cause mortality and with
      cardiac death and/or hospitalization, the pooled RR was 1.44 (95% CI: 1.29-1.61)
      and 1.37 (95% CI: 1.22-1.55), respectively. However, the association disappeared
      on adjustment for B-type natriuretic protein level (RR 1.17, 95% CI: 0.90-1.52)
      and in studies of patients with mean age <65 years (RR 1.23, 95% CI: 0.88
      1.76).We found hypothyroidism associated with increased all-cause mortality as
      well as cardiac death and/or hospitalization in patients with HF. Further
      diagnostic and therapeutic procedures for hypothyroidism may be needed for
      patients with HF. 

PMID- 26222846
TI  - Mild Caloric Restriction Decreases Insulin Requirements in Patients With Type 2
      Diabetes and Severe Insulin Resistance.
AB  - Type 2 diabetes (T2D) affects ~10% of the US population, a subset of whom have
      severe insulin resistance (SIR) (>200 units/d). Treatment of these patients with
      high-dose insulin presents logistical and compliance challenges. We hypothesized
      that mild caloric restriction would reduce insulin requirements in patients with
      T2D and SIR.This was a retrospective study at the National Institutes of Health
      Clinical Center. Inclusion criteria were as follows: T2D, and insulin dose >200
      units/d or >2 units/kg/d. The intervention consisted of mild caloric restriction
      during a 3 to 6-day hospitalization. The major outcomes were change in insulin
      dose and blood glucose from admission to discharge.Ten patients met inclusion
      criteria. Baseline glycated hemoglobin A1c was 10.0 +/- 1.6% and body mass index
      38.8 +/- 9.0 kg/m. Food intake was restricted from 2210 +/- 371 kcal/d
      preadmission to 1810 +/- 202 during the hospital stay (16.5% reduction). Insulin
      dose decreased from 486 +/- 291 units/d preadmission to 223 +/- 127 at discharge
      (44% reduction, P = 0.0025). Blood sugars decreased nonsignificantly in the
      fasting state (from 184 +/- 85 to 141 +/- 42, P = 0.20), before lunch (239 +/- 68
      to 180 +/- 76, P = 0.057), and at bedtime (212 +/- 95 to 176 +/- 48, P = 0.19),
      and significantly decreased before dinner (222 +/- 92 to 162 +/- 70, P =
      0.016).Mild caloric restriction, an accessible and affordable intervention,
      substantially reduced insulin doses in patients with T2D and SIR. Further studies
      are needed to determine if the intervention and results are sustainable outside
      of a hospital setting.

PMID- 26222847
TI  - Effectiveness of Adalimumab in Non-radiographic Axial Spondyloarthritis:
      Evaluation of Clinical and Magnetic Resonance Imaging Outcomes in a Monocentric
      Cohort.
AB  - The primary aim of the study was to evaluate the long-term effectiveness of
      adalimumab (ADA) in a cohort of non-radiographic axial spondyloarthritis (nr
      axSpA), and the secondary aims were to identify predictive factors of response
      and evaluate radiological progression.We evaluated 37 patients (male/female:
      12/25; mean age 49 +/- 14; mean disease duration: 6.3 +/- 5.8) with active nr
      axSpA (Assessment of SpondyloArthritis International Society criteria), despite
      the treatment with >=1 nonsteroidal anti-inflammatory drug for at least 3 months,
      initiating the treatment with ADA 40 mg every other week. Patients were treated
      for 24 months, and evaluated at baseline, 6, 12, and 24 months. Outcome measures
      included Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis
      Functional Index. Radiograph of the spine and sacroiliac joints and magnetic
      resonance of the sacroiliac joints were performed at baseline and according to
      the standard of assessment for the disease.The proportion of patients that
      achieved a BASDAI50 response at 6, 12 and 24 months was 51.3%, 70.3%, and 76.8%,
      respectively. Treatment was well tolerated with no unexpected adverse events
      and/or serious adverse events. All patients remained on treatment for 2 years,
      with a good compliance. We did not identify any predictive factor of response to
      therapy. Moreover, modified Stoke Ankylosing Spondylitis Spine Score and
      Spondyloarthritis Research Consortium of Canada scores showed a trend of
      improvement during the study period.ADA was effective on clinical and
      radiological outcomes at 2-year follow-up; thus, early treatment with ADA may
      prevent radiographic damage and be associated with low disease activity or
      remission. Moreover, data from this cohort study have confirmed safety and
      tolerability profile of ADA in nr-axSpA in the long term.

PMID- 26222848
TI  - Elevated Salivary Alpha-Amylase Level, Association Between Depression and Disease
      Activity, and Stress as a Predictor of Disease Flare in Systemic Lupus
      Erythematosus: A Prospective Case-Control Study.
AB  - Psychological stress has been shown to trigger systemic lupus erythematosus
      (SLE). However, objective evidence of symptom aggravation due to mental stress is
      difficult to identify. We aimed to investigate the relationship between SLE
      disease activity and mental stress, and the usefulness of saliva as an assessment
      index for stress in patients with SLE.We prospectively assessed the salivary
      stress hormone and disease-related biomarkers, and questionnaire data regarding
      stress and depression in 100 patients with SLE and 49 sex- and age-matched normal
      controls (NCs).Patients with SLE had higher mean salivary alpha-amylase levels
      (5.7 +/- 4.6 U/mL vs 2.7 +/- 2.5 U/mL, P < 0.001), anti-chromatin antibody levels
      (25.3 +/- 22.9 U/mL vs 15.9 +/- 10.9 U/mL, P < 0.001), and Beck Depression Index
      (BDI) scores (11.1 +/- 9.2 vs 5.3 +/- 5.1, P < 0.001) than NCs. However, salivary
      cortisol levels and Perceived Stress Scale (PSS) scores did not differ between
      the groups. The BDI scores correlated with the SLE disease activity index
      (SLEDAI) scores (r = 0.253, P = 0.011) and erythrocyte sedimentation rates (r =
      0.234, P = 0.019). SLE patients with the highest-quartile PSS scores had
      significantly increased SLEDAI scores compared to those with the lowest-quartile
      PSS scores after 4 to 5 months' follow-up. Moreover, SLE patients with elevated
      SLEDAI scores had higher baseline PSS scores.Patients with SLE showed uncoupling
      of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis; higher
      salivary alpha-amylase and no different cortisol levels compared with NCs. Also,
      patients with SLE were more depressed, which correlated with disease activity.
      Furthermore, perceived stress was not correlated with disease activity; however,
      disease activity worsened several months later with elevated perceived stress
      levels.

PMID- 26222849
TI  - Revision Surgical Treatment of a Second Lumbar Ewing Sarcoma: A Report of a Rare
      Case.
AB  - We report a case of a 58-year-old man who presented initially with lumbar
      pain.According to radiography, computed tomography, magnetic resonance imaging,
      and bone biopsy results, Ewing sarcoma (ES) was diagnosed. Tumor resection was
      performed, followed by chemotherapy and radiotherapy; pathology confirmed the
      diagnosis of ES. After surgery, the tumor recurred twice with progressive
      symptoms, meriting repeated excisional surgery. At the 4-year follow-up, the
      patient showed apparent improvement, with return of function and strength and
      resolution of pain.We discuss its clinical features and treatment in the light of
      the current knowledge. 

PMID- 26222850
TI  - Synchronous Resectable Metastatic Colorectal Cancer: Lymph Node Involvement
      Predicts Poor Outcome.
AB  - To evaluate the value of lymph node status of primary tumors in predicting the
      prognosis of synchronous resectable metastatic colorectal cancer (mCRC).The
      characteristics of resectable mCRC are substantially different from other
      cancers, and the prognostic factors of resectable mCRC are still
      controversial.The data of 2007 patients with mCRC who received resection of the
      primary tumors and metastatic lesions synchronously were reviewed from the
      Surveillance, Epidemiology and End-Result database. The Kaplan-Meier method was
      used to evaluate the capacity of different prognostic factors. Univariate and
      multivariate logistic regression models were used to evaluate the relationship
      between the lymph node status and other factors. The mRNA profiles of primary
      resectable mCRC tumors were obtained by microarray at our center.The median
      survival times were 50, 36, 32, 27, and 19 months in the N0-stage, N1a-stage, N1b
      stage, N2a-stage, and N2b-stage subgroups according to the 7th American Joint
      Committee on Cancer (AJCC) Tumor Lymph Node Metastasis (TNM) N-classification (P
      = 0.000), and 40, 29, 22, and 15 months in patients with metastatic lymph node
      ratio (LNR) <0.25, 0.25-0.49, 0.5-0.74, and >=0.75 subgroups (P = 0.000). In the
      COX model, the 7th AJCC TNM N-stage and LNR were independent prognostic factors.
      The mRNA profile was not associated with lymph node involvement.Both the N-stage
      according to the 7th AJCC TNM staging system and LNR had the capacity to
      subclassify synchronous resectable mCRC with different prognoses. The lymph node
      might be integrated into the AJCC staging system as a diagnose-delay prognostic
      factor for stage IV disease.

PMID- 26222851
TI  - Plasma Cardiotrophin-1 as a Marker of Hypertension and Diabetes-Induced Target
      Organ Damage and Cardiovascular Risk.
AB  - The search for biomarkers of hypertension and diabetes-induced damage to multiple
      target organs is a priority. We analyzed the correlation between plasma
      cardiotrophin-1 (CT-1), a chemokine that participates in cardiovascular
      remodeling and organ fibrosis, and a wide range of parameters currently used to
      diagnose morphological and functional progressive injury in left ventricle,
      arteries, and kidneys of diabetic and hypertensive patients, in order to validate
      plasma levels of CT-1 as clinical biomarker.This is an observational study with
      93 type 2-diabetic patients, 209 hypertensive patients, and 82 healthy controls
      in which we assessed the following parameters: plasma CT-1, basal glycaemia,
      systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure
      (PP), left ventricular hypertrophy (LVH by electrocardiographic indexes),
      peripheral vascular disease (by pulse wave velocity-PWV, carotid intima-media
      thickness-C-IMT, and ankle-brachial index-ABI), and renal impairment (by
      microalbuminuria, albumin/creatinine urinary ratio, plasma creatinine
      concentrations, and glomerular filtration rate).Hypertensive or diabetic patients
      have higher plasma CT-1 than control patients. CT-1 positively correlates with
      basal glycaemia, SBP, DBP, PP, LVH, arterial damage (increased IMT, decreased
      ABI), and early renal damage (microalbuminuria, elevated albumin/creatinine
      ratio). CT-1 also correlates with increased 10-year cardiovascular risk. Multiple
      linear regression analysis confirmed that CT-1 was associated with arterial
      injury assessed by PWV, IMT, ABI, and cardiac damage evaluated by Cornell voltage
      duration product.Increases in plasma CT-1 are strongly related to the intensity
      of several parameters associated to target organ damage supporting further
      investigation of its diagnostic capacity as single biomarker of cardiovascular
      injury and risk and, possibly, of subclinical renal damage. 

PMID- 26222852
TI  - Longitudinal Evaluation of Cornea With Swept-Source Optical Coherence Tomography
      and Scheimpflug Imaging Before and After Lasik.
AB  - Swept-source optical coherence tomography (OCT) is the latest advancement in
      anterior segment imaging. There are limited data regarding its performance after
      laser in situ keratomileusis (LASIK). We compared the reliability of swept-source
      OCT and Scheimpflug imaging for evaluation of corneal parameters in refractive
      surgery candidates with myopia or myopic astigmatism. Three consecutive
      measurements were obtained preoperatively and 1 year postoperatively using swept
      source OCT and Scheimpflug imaging. The study parameters included central corneal
      thickness (CCT), thinnest corneal thickness (TCT), keratometry at steep (Ks) and
      flat (Kf) axes, mean keratometry (Km), and, anterior and posterior best fit
      spheres (Ant and Post BFS). The main outcome measures included reliability of
      measurements before and after LASIK was evaluated using intraclass correlation
      coefficient (ICC) and reproducibility coefficients (RC). Association between the
      mean value of corneal parameters with age, spherical equivalent (SEQ), and
      residual bed thickness (RBT) and association of variance heterogeneity of corneal
      parameters and these covariates were analyzed. Twenty-six right eyes of 26
      participants (mean age, 32.7 +/- 6.9 yrs; mean SEQ, -6.27 +/- 1.67 D) were
      included. Preoperatively, swept-source OCT demonstrated significantly higher ICC
      for Ks, CCT, TCT, and Post BFS (P <= 0.016), compared with Scheimpflug imaging.
      Swept-source OCT demonstrated significantly smaller RC values for CCT, TCT, and
      Post BFS (P <= 0.001). After LASIK, both devices had significant differences in
      measurements for all corneal parameters (P <= 0.015). Swept-source OCT
      demonstrated a significantly higher ICC and smaller RC for all measurements,
      compared with Scheimpflug imaging (P <= 0.001). Association of variance
      heterogeneity was only found in pre-LASIK Ant BFS and post-LASIK Post BFS for
      swept-source OCT, whereas significant association of variance heterogeneity was
      noted for all measurements except Ks and Km for Scheimpflug imaging.This study
      reported higher reliability of swept-source OCT for post-LASIK corneal
      measurements, as compared with Scheimpflug imaging. The reliability of corneal
      parameters measured with Scheimpflug imaging after LASIK was not consistent
      across different age, SEQ, and RBT measurements. These factors need to be
      considered during follow-up and evaluation of post-LASIK patients for further
      surgical procedures.

PMID- 26222853
TI  - Acute Anticholinesterase Pesticide Poisoning Caused a Long-Term Mortality
      Increase: A Nationwide Population-Based Cohort Study.
AB  - Acute anticholinesterase pesticide (organophosphate and carbamate) poisoning
      (ACPP) often produces severe complications, and sometimes death. We investigated
      the long-term mortality of patients with ACPP because it is not sufficiently
      understood. In this retrospective nationwide population-based cohort study, 818
      patients with ACPP and 16,360 healthy comparisons from 1999 to 2010 were selected
      from Taiwan's National Health Insurance Research Database. They were followed
      until 2011. Ninety-four (11.5%) ACPP patients and 793 (4.9%) comparisons died (P
      < 0.01) during follow-up. The incidence rate ratios (IRRs) of death were 2.5
      times higher in ACPP patients than in comparisons (P < 0.01). The risk of death
      was particularly high in the first month after ACPP (IRR: 92.7; 95% confidence
      interval [CI]: 45.0-191.0) and still high for ~6 months (IRR: 3.8; 95% CI: 1.9
      7.4). After adjusting for age, gender, selected comorbidities, geographic area,
      and monthly income, the hazard ratio of death for ACPP patients was still 2.4
      times higher than for comparisons. Older age (>=35 years), male gender, diabetes
      mellitus, coronary artery disease, hypertension, stroke, mental disorder, and
      lower monthly income also predicted death. ACPP significantly increased long-term
      mortality. In addition to early follow-up after acute treatment, comorbidity
      control and socioeconomic assistance are needed for patients with ACPP.

PMID- 26222854
TI  - Risk Models of Operative Morbidities in 16,930 Critically Ill Surgical Patients
      Based on a Japanese Nationwide Database.
AB  - The aim of the study was to evaluate preoperative variables predictive of lethal
      morbidities in critically ill surgical patients at a national level.There is no
      report of risk stratification for morbidities associated with mortality in
      critically ill patients with acute diffuse peritonitis (ADP).We examined data
      from 16,930 patients operated during 2011 and 2012 in 1546 different hospitals
      for ADP identified in the National Clinical Database of Japan. We analyzed
      morbidities significantly associated with operative mortality. Based on 80% of
      the population, we calculated independent predictors for these morbidities. The
      risk factors were validated using the remaining 20%.The operative mortality was
      14.1%. Morbidity of any grade occurred in 40.2% of patients. Morbidities
      correlated with mortality, including septic shock, progressive renal
      insufficiency, prolonged ventilation >48 hours, systemic sepsis, central nervous
      system (CNS) morbidities, acute renal failure and pneumonia, and surgical site
      infection (SSI), were selected for risk models. A total of 18 to 29 preoperative
      variables were selected per morbidity and yielded excellent C-indices for each
      (septic shock: 0.851; progressive renal insufficiency: 0.878; prolonged
      ventilation >48 h: 0.849; systemic sepsis: 0.839; CNS morbidities: 0.848; acute
      renal failure: 0.868; pneumonia: 0.830; and SSI: 0.688).We report the first risk
      stratification study on lethal morbidities in critically ill patients with ADP
      using a nationwide surgical database. These risk models will contribute to
      patient counseling and help predict which patients require more aggressive
      surgical and novel pharmacological interventions.

PMID- 26222855
TI  - Rosuvastatin Treatment for Preventing Contrast-Induced Acute Kidney Injury After
      Cardiac Catheterization: A Meta-Analysis of Randomized Controlled Trials.
AB  - We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate
      the protective effects of rosuvastatin on contrast-induced acute kidney injury
      (CI-AKI) and major adverse cardiovascular events (MACEs) in patients undergoing
      cardiac catherization.PubMed, MEDLINE, Web of Science, EMBASE,
      ClinicalTrials.gov, and the Cochrane Central RCTs were searched for RCTs from
      inception to May 2015, to compare rosuvastatin for preventing CI-AKI with placebo
      treatment in patients undergoing cardiac catherization.Five RCTs with a total of
      4045 patients involving 2020 patients pretreated with rosuvastatin and 2025
      control patients were identified and analyzed. Patients treated with rosuvastatin
      had a 51% lower risk of CI-AKI compared with the control group based on a fixed
      effect model (OR = 0.49, 95% CI = 0.37-0.66, P < 0.001), and showed a trend
      toward a reduced risk of MACEs (OR = 0.62, 95% CI = 0.36-1.07, P = 0.08). A
      subgroup analysis showed that studies with Jadad score >=3 showed a significant
      reduction of CI-AKI (OR = 0.53, 95% CI, 0.38-0.73, P < 0.001). However, the risk
      of CI-AKI did not significantly differ in the studies with Jadad score <3 (OR =
      0.54, 95% CI, 0.13-2.24, P = 0.40). In addition, the rosuvastatin treatment
      showed no effect for preventing CI-AKI in patients with chronic kidney disease
      (CKD) undergoing elective cardiac catherization (I = 0%, OR = 0.81, 95% CI = 0.41
      1.61, P = 0.55).This updated meta-analysis demonstrated that preprocedural
      rosuvastatin treatment could significantly reduce the incidence of CI-AKI, with a
      trend toward a reduced risk of MACEs in patients undergoing cardiac
      catheterization. However, rosuvastatin treatment did not seem to be effective for
      preventing CI-AKI in CKD patients undergoing elective cardiac catheterization.

PMID- 26222856
TI  - Diameter-Axial-Polar Nephrometry is Predictive of Surgical Outcomes Following
      Partial Nephrectomy.
AB  - This study sought to evaluate the predictive value of the DAP (diameter-axial
      polar) nephrometry system on surgical outcomes following partial nephrectomy
      (PN).This was a retrospective study of 237 patients who underwent open or
      minimally invasive PN for renal tumors at a single tertiary care center between
      2009 and 2013. The primary outcomes included ischemia time >20 minutes and
      percentage of estimated glomerular filtration rate (eGFR) decline >10%.
      Statistical analysis was performed to study associations and predictions.The DAP
      sum score exhibited a statistically significant correlation with ischemia time,
      operative time (OT), estimated blood loss (EBL), length of hospital stay (LOS),
      and percent change in eGFR. The DAP sum score (odds ratio [OR]: 1.749; 95%
      confidence interval [CI] 1.379-2.220; P < 0.001) and conventional laparoscopy and
      laparo-endoscopic single-site (CL&LESS) surgery versus the open surgical approach
      (OR: 5.736; 95% CI: 2.529-13.011; P < 0.001) independently predicted an ischemia
      time >20 minutes. Similarly, the DAP sum score (OR: 1.297; 95% CI 1.051-1.602; P
      = 0.016), age-weighted Charlson comorbidity index (CCI) (OR: 4.730; 95% CI 1.463
      15.291; P = 0.009), EBL (OR 2.433; 95% CI 1.095-5.407; P = 0.029), and ischemia
      time (OR 3.332; 95% CI 1.777-6.249; P < 0.001) were identified as independent
      predictors of eGFR decline >10%. Furthermore, the DAP score * ischemia time
      interactions were statistically significant (P < 0.001).We confirmed the
      predictive value of the DAP nephrometry score with respect to ischemia time and
      renal functional decline in an independent external cohort of patients undergoing
      PN. The effect of the DAP score on renal functional decline partially depends on
      that of ischemia time, and the individual component DAP scores may have different
      effects on clinical outcomes.

PMID- 26222857
TI  - Shoulder Dysfunction After Radiotherapy in Surgically and Nonsurgically Treated
      Necks: A Prospective Study.
AB  - Our goal was to evaluate the shoulder dysfunction after radiotherapy in
      surgically and nonsurgically treated necks.A prospective pair matched design was
      performed. A total of 96 patients from 3 groups were enrolled in the study. The
      patients were asked to complete the shoulder domain section of the University of
      Washington Quality of Life questionnaire on 2 occasions: preoperatively and 12
      months postoperatively.None of the patients had a shoulder impairment before the
      operation. At the follow-up session, 4 patients who had received radiotherapy
      only reported mild shoulder dysfunction, the mean score was 96.3, the difference
      was significant compared with the preoperative score (P = 0.046). For patients
      who had received neck dissection, 7 patients reported that the impaired shoulder
      function caused them to change their work and 14 patients reported that their
      shoulder function was affected a little; the mean score was 71.6. For patients
      who had received both neck dissection and postoperative radiotherapy, 9 patients
      reported that they had changed their work due to shoulder dysfunction and 16
      patients reported mild shoulder impairment; the mean score was 65.3 and the
      difference was not significant (P = 0.304).Radiotherapy does not increase
      shoulder dysfunction in surgically treated necks, but it could induce shoulder
      impairment in nonsurgically treated necks.

PMID- 26222858
TI  - Early-Onset Neonatal Sepsis: Still Room for Improvement in Procalcitonin
      Diagnostic Accuracy Studies.
AB  - To perform a systematic review assessing accuracy and completeness of diagnostic
      studies of procalcitonin (PCT) for early-onset neonatal sepsis (EONS) using the
      Standards for Reporting of Diagnostic Accuracy (STARD) initiative.EONS, diagnosed
      during the first 3 days of life, remains a common and serious problem. Increased
      PCT is a potentially useful diagnostic marker of EONS, but reports in the
      literature are contradictory. There are several possible explanations for the
      divergent results including the quality of studies reporting the clinical
      usefulness of PCT in ruling in or ruling out EONS.We systematically reviewed
      PubMed, Scopus, and the Cochrane Library databases up to October 1, 2014. Studies
      were eligible for inclusion in our review if they provided measures of PCT
      accuracy for diagnosing EONS. A data extraction form based on the STARD checklist
      and adapted for neonates with EONS was used to appraise the quality of the
      reporting of included studies.We found 18 articles (1998-2014) fulfilling our
      eligibility criteria which were included in the final analysis. Overall, the
      results of our analysis showed that the quality of studies reporting diagnostic
      accuracy of PCT for EONS was suboptimal leaving ample room for improvement.
      Information on key elements of design, analysis, and interpretation of test
      accuracy were frequently missing.Authors should be aware of the STARD criteria
      before starting a study in this field. We welcome stricter adherence to this
      guideline. Well-reported studies with appropriate designs will provide more
      reliable information to guide decisions on the use and interpretations of PCT
      test results in the management of neonates with EONS. 

PMID- 26222859
TI  - Sustained Virologic Response to a Dual Peginterferon alfa-2a and Ribavirin in
      Treating Chronic hepatitis C Infection: A Retrospective Cohort Study.
AB  - In Myanmar, hepatitis C virus (HCV) infection prevalence is 2%. A combination
      therapy of pegylated interferon alfa-2a and ribavirin (PEG-IFNa/RBV) is a
      standard treatment, but the effect of this antiviral therapy needs evaluation as
      to determine the efficacy and safety of dual PEG-IFNa/RBV therapy in treating
      patients infected with HCV in Myanmar.This was a retrospective analysis of data
      from a single clinic exclusively for gastrointestinal diseases in Yangon,
      Myanmar. We assessed treatment responses at the defined time points and
      stratified by genotypes of HCV. We also determined incidences of adverse events
      (AEs). We investigated independent predictors of sustained virologic response
      (SVR) in the participants.A total of 362 HCV-infected cases were included in this
      study. The majority were females (51.7%) with mean age of 47.12 years (+/-11.6)
      and noncirrhosis patients (82%). Rapid virologic response (RVR), early virologic
      response (EVR), end of treatment response (ETR), and SVR 24 weeks after
      completion of the dual treatment were 50.3% (178/362), 88% (314/357), 80.1%
      (286/357), and 85.6% (167/195), respectively. The most frequently reported AEs
      were nausea/anorexia (72.8%) and flu-like symptoms (62.4%). In multivariate
      analysis, 4 factors were independently associated with SVR; SVR to genotype 3
      (odds ratio [OR] 2.4, 95% CI: 1.24-4.62), EVR (OR 0.54, 95% CI: 0.3-0.95), and
      duration of treatment (OR 1.52, 95% CI: 1.18-1.98). Study limitations were
      acknowledged.The efficacy and safety of the dual therapy in treating HCV-infected
      patient in Myanmar was acceptable. We recommend a prospective randomized control
      trial looking at duration of therapy and rates of achieving SVR, which could
      significantly impact the care of HCV-infected patients in Myanmar and perhaps
      other countries as well. 

PMID- 26222860
TI  - MELD Score Kinetics in Decompensated HIV+/HCV+ Patients: A Useful Prognostic Tool
      (ANRS HC EP 25 PRETHEVIC Cohort Study).
AB  - To assess prognostic factors for survival and describe Model for End-Stage liver
      disease (MELD) dynamics in human immunodeficiency virus+/hepatitis C virus+
      (HIV+/HCV+) patients after an initial episode of hepatic decompensation.An
      HIV+/HCV+ cohort of patients experiencing an initial decompensation episode
      within the year preceding enrollment were followed prospectively. Clinical and
      biological data were collected every 3 months. Predictors for survival were
      identified using Kaplan-Meier curves and Cox models. A 2-slope-mixed linear model
      was used to estimate MELD score changes as a function of survival.Sixty seven
      patients were included in 32 centers between 2009 and 2012 (72% male; median age:
      48 years [interquartile ratio (IQR):45-52], median follow-up: 22.4 months [range:
      0.5-65.3]). Overall survival rates were 86%, 78%, and 59% at 6, 12, and 24
      months, respectively. Under multivariate analysis, the MELD score at initial
      decompensation was predictive of survival, adjusted for age, type of
      decompensation, baseline CD4 counts, and further decompensation during follow-up
      as a time-dependent variable. The adjusted hazard ratio of death was 1.32 for a
      score 3 points higher (95% CI: [1.06-1.63], P = 0.012). MELD score kinetics
      within the 6 months after initial decompensation differed significantly between
      non-deceased and deceased patients, with a decreased (-0.49/month; P = 0.016),
      versus a flat (+0.06/month, P = 0.753) mean change in score.MELD is an effective
      tool to predict survival in HIV+/HCV+ patients with decompensated cirrhosis. A
      non-decreasing MELD score within 6 months following this initial decompensation
      episode may benefit from privileged access to liver transplantation in this poor
      prognosis population.

PMID- 26222861
TI  - Enhanced Estimates of the Influenza Vaccination Effect in Preventing Mortality: A
      Prospective Cohort Study.
AB  - Mortality is a major end-point in the evaluation of influenza vaccine
      effectiveness. However, this effect is not well known, since most previous
      studies failed to show good control of biases. We aimed to estimate the
      effectiveness of influenza vaccination in preventing all-cause mortality in
      community-dwelling seniors.Since 2009, a population-based cohort study using
      healthcare databases has been conducted in Navarra, Spain. In 2 late influenza
      seasons, 2011/2012 and 2012/2013, all-cause mortality in the period January to
      May was compared between seniors (65 years or over) who received the trivalent
      influenza vaccine and those who were unvaccinated, adjusting for demographics,
      major chronic conditions, dependence, previous hospitalization, and pneumococcal
      vaccination.The cohort included 103,156 seniors in the 2011/2012 season and
      105,140 in the 2012/2013 season (58% vaccinated). Seniors vaccinated in the
      previous season who discontinued vaccination (6% of the total) had excess
      mortality and were excluded to prevent frailty bias. The final analysis included
      80,730 person-years and 2778 deaths. Vaccinated seniors had 16% less all-cause
      mortality than those unvaccinated (adjusted rate ratio [RR] = 0.84; 95%
      confidence interval 0.76-0.93). This association disappeared in the post
      influenza period (adjusted RR = 0.96; 95% confidence interval 0.85-1.09). A
      similar comparison did not find an association in January to May of the 2009/2010
      pandemic season (adjusted RR = 0.98; 95% confidence interval 0.84-1.14), when no
      effect of the seasonal vaccine was expected. On average, 1 death was prevented
      for every 328 seniors vaccinated: 1 for every 649 in the 65 to 74 year age group
      and 1 for every 251 among those aged 75 and over.These results suggest a moderate
      preventive effect and a high potential impact of the seasonal influenza vaccine
      against all-cause mortality. This reinforces the recommendation of annual
      influenza vaccination in seniors.

PMID- 26222862
TI  - Use of Extracorporeal Membrane Oxygenation to Rescue Patients With Refractory
      Ventricular Arrhythmia in Acute Myocardial Infarction.
AB  - Refractory ventricular arrhythmia is a serious problem in acute myocardial
      infarction (AMI), with an extremely high mortality rate and limited effective
      treatment. Extracorporeal membrane oxygenation (ECMO) is useful to rescue
      patients with cardiopulmonary collapse. However, little is known about whether
      ECMO is a potential rescue technique for patients with refractory ventricular
      arrhythmia in AMI.We retrospectively analyzed prospectively collected data on
      patients with AMI and refractory ventricular arrhythmia who underwent ECMO as
      rescue therapy and the bridge to revascularization from February 2001 to January
      2013. Primary endpoint was mortality on index admission, and secondary endpoint
      was mortality on index admission or advanced brain damage at discharge.A total of
      69 (62 men) patients were enrolled in this study. During the index admission, 39
      patients (56.5%) met primary endpoint, and 45 patients (65.2%) met secondary
      endpoint, respectively. In multivariate Cox regression analysis, both the
      presence of profound anoxic encephalopathy and acute renal failure requiring
      dialysis were significant predictive factors for both primary and secondary
      endpoints.ECMO is a feasible rescue therapy and bridge to revascularization in
      patients with refractory ventricular arrhythmia in acute myocardial infarction.
      The presence of profound anoxic encephalopathy and acute renal failure requiring
      dialysis were significant prognostic factors. 

PMID- 26222863
TI  - Risk Factors for Acute and Early HIV Infection Among Men Who Have Sex With Men
      (MSM) in San Diego, 2008 to 2014: A Cohort Study.
AB  - The objectives of this study were to identify risk factors associated with acute
      and early HIV infection (AEH) among men who have sex with men (MSM) undergoing
      community HIV testing and to compare demographics in those diagnosed with AEH
      with those diagnosed at chronic stage of HIV infection.In this retrospective
      cohort study, we analyzed risk factors associated with AEH among 8925 unique MSM
      (including 200 with AEH [2.2%] and 219 [2.5%] with newly diagnosed chronic HIV
      infection) undergoing community-based, confidential AEH screening in San Diego,
      California.The combination of condomless receptive anal intercourse (CRAI) plus
      >=5 male partners, CRAI with an HIV-positive male, CRAI with a person who injects
      drugs, and prior syphilis diagnosis were significant predictors of AEH in the
      multivariable Cox regression model. Individuals reporting >=1 of these 4 risk
      factors had a hazard ratio of 4.6 for AEH. MSM diagnosed with AEH differed in
      race (P = 0.005; more reported white race [P = 0.001], less black race [P =
      0.030], trend toward less Native American race [P = 0.061]), when compared to
      those diagnosed with chronic HIV infection, while there was no difference
      observed regarding age.We established a multivariate model for the predicting
      risk of AEH infection in a cohort of MSM undergoing community HIV screening,
      which could be potentially used to discern those in need of further HIV nucleic
      acid amplification testing for community screening programs that do not test
      routinely for AEH. In addition, we found that race differed between those
      diagnosed with AEH and those diagnosed at chronic stage of HIV infection
      underlining the need for interventions that reduce stigma and promote the uptake
      of HIV testing for black MSM.

PMID- 26222864
TI  - Membranous Nephropathy Associated With Immunological Disorder-Related Liver
      Disease: A Retrospective Study of 10 Cases.
AB  - The association between membranous nephropathy (MN) and immunological disorder
      related liver disease has not been extensively investigated, and the specific
      features of this uncommon association, if any, remain to be determined.We
      retrospectively identified 10 patients with this association. We aimed to
      describe the clinical, biological, and pathological characteristics of these
      patients and their therapeutic management. The possible involvement of the
      phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was
      assessed by immunohistochemistry with renal and liver biopsy specimens.The mean
      delay between MN and liver disease diagnoses was 3.9 years and the interval
      between the diagnosis of the glomerular and liver diseases was <1.5 years in 5
      patients. MN was associated with a broad spectrum of liver diseases including
      primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary
      sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC
      (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease.
      Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test
      was performed under specific immunosuppressive treatment in 3 out of 9 patients.
      Seven of the 9 patients with available renal tissue specimens displayed enhanced
      expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver
      parenchyma from these patients or in normal liver tissue. The study of
      immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most
      frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4
      predominating.Detection of PLA2R antibodies in glomeruli but not in liver
      parenchyma is a common finding in patients with MN associated with autoimmune
      liver disease, suggesting that these autoantibodies are not exclusively detected
      in idiopathic MN.

PMID- 26222865
TI  - Laparoscopy Versus Laparotomy in the Treatment of High-Risk Endometrial Cancer: A
      Propensity Score Matching Analysis.
AB  - The aim of this study was to compare the long-term safety and efficacy of
      laparoscopic surgery and laparotomy for high-risk endometrial cancer (EC).A
      retrospective analysis based on our decade of clinical data of patients with high
      risk EC who were comprehensively surgically staged by laparotomy or laparoscopy
      was performed. The surgical outcomes were compared between different approaches
      using propensity score matching (PSM).Eighty-one pairs of patients from the
      initial 220 enrolled ones were matched by PSM. The mean operative time is similar
      between laparotomy and laparoscopy groups (258 minutes vs. 253 minutes). The
      laparoscopy cohort has less blood loss (107 mL vs.414 mL, P < 0.01), shorter
      hospital stay (14.7 days vs. 17.7 days, P = 0.02) and significant fewer
      intraoperative complications (6.2% vs. 25.9%, P < 0.01). The pelvic lymph nodes
      dissected by laparoscopy (16.4) were significant less than that dissected by
      laparotomy (21.9). The 5- and 10-year survival rate for laparotomy were 89.2% and
      75.8% compared with 85.3% and 85.3% for the laparoscopy. There was no significant
      difference in overall survival (P = 0.97).Laparoscopy is as effective as
      laparotomy in the long term and can be safely carried out in patients with high
      risk EC for surgery treatment.

PMID- 26222867
TI  - Massive Pulmonary Calculi Embolism: A Novel Complication of Pneumatic
      Lithotripsy: A Case Report.
AB  - Pneumatic lithotripsy is a minimally invasive technique mainly for the treatment
      of urinary staghorn stones. Previous literatures have reported some therapeutic
      complications during or after this procedure, but calculi embolism has not been
      mentioned before.We report here a fatal case of calculi-induced pulmonary
      embolism in an adult woman who underwent pneumatic lithotripsy. An autopsy did
      not reveal any evidence of pulmonary embolism. However, light microscopy revealed
      noticeable presence of calculi in pulmonary arterioles and capillaries, as
      evidenced by environmental scanning electron microscope and energy dispersive X
      ray analysis. The primary determinants of calculi embolism include intrarenal
      pressure, and volume and viscosity of the calculi fragments formation. Vascular
      intravasation of smashed calculi might increase pulmonary vascular resistance and
      hypoxemia and decrease cardiac output.This case report intends to provide
      information for clinicians to consider the probability of intraoperative calculi
      embolism during lithotripsies when patients develop typical symptoms of acute
      pulmonary embolism. 

PMID- 26222866
TI  - Brain Metabolism of Less-Educated Patients With Alzheimer Dementia Studied by
      Positron Emission Tomography.
AB  - Alzheimer dementia (AD) is the commonest form of dementia. Although illiteracy is
      associated with high prevalence of dementia of the Alzheimer type (DAT), their
      relationship is still unclear. Nevertheless, mild DAT in illiterate participants
      seems to be due to brain atrophy.In this study, we compared the impact of brain
      metabolism efficiency in healthy participants and less-educated patients with
      mild DAT using 2-fluoro-2-deoxy-D-glucose (F-FDG-PET) positron emission
      tomography. Out of 43 eligible less-educated participants with dementia, only 23
      (14 women and 9 men) met Diagnostic and Statistical Manual (DSM)-III-R or DSM-IV
      criteria for DAT and AD and were included. Participants with intracranial insults
      were excluded by brain magnetic resonance imaging and participants with metabolic
      or systemic conditions were excluded by blood sampling. In addition, 16
      cognitively normal elderly (age >70 years), including 7 women and 9 men, were
      enrolled in the sham group. The PET imaging data were analyzed using statistical
      parametric mapping (SPM8) to determine reliability and specificity.Glucose
      metabolic rate was low in the DAT group, especially in the middle temporal gyrus,
      middle frontal gyrus, superior frontal gyrus, inferior frontal gyrus, posterior
      cingulate gyrus, angular gyrus, parahippocampal gyrus, middle occipital gyrus,
      rectal gyrus, and lingual gyrus.Our results showed that DAT patients with less
      education not only have prominent clinical signs and symptoms related to dementia
      but also decreased gray matter metabolism. 

PMID- 26222868
TI  - Total Laparoscopic Versus Laparotomic Radical Hysterectomy and Lymphadenectomy in
      Cervical Cancer: An Observational Study of 13-Year Experience.
AB  - This article aims to review our 13-year experience in the treatment of patients
      with cervical cancer by comparing total laparoscopic radical hysterectomy and
      lymphadenectomy with laparotomy.We reviewed all patients undergoing total
      laparoscopic or laparotomic radical hysterectomy and lymphadenectomy because of
      cervical cancer between 2001 and 2014 in our hospital.In total, 154 eligible
      patients with International Federation of Gynecology and Obstetrics Ia-IIb were
      enrolled, including 106 patients undergoing total laparoscopic procedure and 48
      patients undergoing laparotomic procedure. In the present study, patients in
      total laparoscopy group were associated with superior surgical outcomes, such as
      significantly lower blood transfusion compared to those in laparotomy group.
      Furthermore, patients had significantly lower postoperative complication rate in
      total laparoscopy group compared with that in laparotomy group (24.5% vs 52.1%)
      (P = 0.001). Three patients (2.8%) in total laparoscopy group had unplanned
      conversion to laparotomy. Disease-free survival rates were 89.7% and 88.9% in
      total laparoscopy and laparotomy groups (P = 0.39), respectively, and overall
      survival rates were 90.2% in total laparoscopy group and 91.3% in laparotomy
      group (P = 0.40).Total laparoscopic procedure is a surgically and oncologically
      safe and reliable alternative to laparotomic procedure in the treatment for
      cervical cancer.

PMID- 26222869
TI  - Genetic Association Between CD143 rs4340 Polymorphism and Pneumonia risk: A Meta
      Analysis.
AB  - rs4340 polymorphism at intron 16 of the angiotensin-converting enzyme (CD143)
      gene was reported to repress cough reflex by reducing bradykinin and substance P
      levels, thus increasing the likelihood to develop pneumonia. There have been
      different reports regarding the correlation of CD143 rs4340 genotypes with
      pneumonia risk, which prompted us to perform a meta-analysis to determine the
      elusive association.We combined multiple keywords to identify the studies
      addressing the association between CD143 rs4340 genotypes and pneumonia risk
      covered in the EMBASE, Google Scholar, PubMed, and CNKI databases. Odds ratios
      (ORs) and 95% confidence intervals (CIs) were calculated to assess the risk of
      pneumonia. The fixed-effects model (FEM) was used.A total of 10 studies were
      analyzed in this quantitative analysis. We found a strong association between
      rs4340 single nucleotide polymorphism (SNP) and pneumonia risk using the
      recessive model (FEM: OR 1.33, 95% CI 1.13-1.57). A significantly increased risk
      was also indicated under the recessive model in Asian populations (FEM: OR 1.57,
      95% CI 1.19-2.07), community-acquired pneumonia (CAP) (FEM: OR 1.31, 95% CI 1.08
      1.60), and nosocomial pneumonia (NP) (FEM: OR 1.52, 95% CI 1.06-2.19).Our meta
      analysis demonstrates that CD143 rs4340 polymorphism may represent a risk factor
      for pneumonia. 

PMID- 26222870
TI  - D-Dimer Can Serve as a Prognostic and Predictive Biomarker for Metastatic Gastric
      Cancer Treated by Chemotherapy.
AB  - Systemic activation of hemostasis and thrombosis has been implicated in tumor
      progression and metastasis. D-dimer has been used as an indicator for the
      thrombosis. Here, we investigated the role of the activation of coagulation in
      patients with metastatic gastric cancer by measuring D-dimer level.We conducted
      an observation study of 46 metastatic gastric cancer patients who received
      palliative chemotherapy (CTx). D-dimer levels were assessed before CTx and at the
      first response evaluation after CTx.The overall survival (OS) of patients with
      pretreatment D-dimer levels <1.5 MUg/mL was significantly longer than that of
      patients with D-dimer levels >=1.5 MUg/mL (22.0 vs 7.9 months, P = 0.019). At the
      first response evaluation, the mean level of D-dimer was significantly decreased
      by 2.11 MUg/mL in patients either with partial response or stable disease (P =
      0.011) whereas the mean level of D-dimer, although the difference did not reach
      statistical significance, was increased by 2.46 MUg/mL in patients with
      progressive disease. In addition, the OS of patients with D-dimer levels <1.0
      MUg/mL at the first response evaluation was significantly longer than that of
      patients with D-dimer levels >=1.0 MUg/mL (22.0 vs 7.0 months, P = 0.009). The
      lower D-dimer levels (<1.0 MUg/mL) at the first response evaluation after CTx was
      independent predictive factor for better survival in multivariate analysis (P =
      0.037).This study suggests that D-dimer levels may serve as a biomarker for
      response to CTx and OS in patients with metastatic gastric cancer.

PMID- 26222872
TI  - Exploring Statins to Decrease HIV-Related Heart Disease Risk.

PMID- 26222871
TI  - Epigenetic Modifications and Accumulation of DNA Double-Strand Breaks in Oral
      Lichen Planus Lesions Presenting Poor Response to Therapy.
AB  - Epigenetics refers to changes in cell characteristics that occur independently of
      modifications to the deoxyribonucleic acid (DNA) sequence. Alterations mediated
      by epigenetic mechanisms are important factors in cancer progression. Although an
      exciting prospect, the identification of early epigenetic markers associated with
      clinical outcome in premalignant and malignant disorders remains elusive. We
      examined alterations in chromatin acetylation in oral lichen planus (OLP) with
      distinct clinical behavior and compared the alterations to the levels of DNA
      double-strand breaks (DSBs). We analyzed 42 OLP patients, who had different
      responses to therapy, for acetyl-histone H3 at lys9 (H3K9ac), which is associated
      with enhanced transcription and nuclear decondensation, and the presence of DSBs,
      as determined by accumulation of phosphorylated gammaH2AX foci. Patients with
      high levels of H3K9ac acetylation failed to respond to therapy or experienced
      disease recurrence shortly after therapy. Similar to H3K9ac, patients who
      responded poorly to therapy had increased accumulation of DNA DSB, indicating
      genomic instability. These findings suggest that histone modifications occur in
      OLP, and H3K9ac and gammaH2AX histones may serve as epigenetic markers for OLP
      recurrence. 

PMID- 26222873
TI  - Testing for Drugs in Exhaled Breath Collected With ExaBreath in a Drug Dependence
      Population: Comparison With Data Obtained in Urine After Liquid Chromatographic
      Tandem Mass Spectrometric Analyses.
AB  - BACKGROUND: Exhaled breath is commonly used in alcohol testing but has been
      recently demonstrated by scientists from Sweden, Switzerland, and the United
      States to contain a large number of both volatile and nonvolatile substances that
      can be measured using dedicated devices. ExaBreath is a sampling device that
      collects the bio-aerosols particles from the donor. Approximately 1-2 minutes
      exhaled breath is enough for the test. The device collects the very small bio
      aerosols on a filter, which is consecutively incubated into methanol to release
      the drugs at the laboratory. METHODS: Eighteen drug addicts from a methadone
      substitution program were recruited for this study. There were 5 women and 13
      men, aged 25-50 years. The daily methadone dosage ranged from 10 to 120 mg,
      mostly as syrup. Urine (in plastic tubes with no preservative) and exhaled breath
      were simultaneously collected. In both fluids, methadone and 2-ethylidene-1,5
      dimethyl-3,3-diphenylpyrrolidine (EDDP) were tested using a specific liquid
      chromatographic-tandem mass spectrometric method, whereas all other compounds
      were screened by liquid chromatographic-tandem mass spectrometric method using a
      home made library of more than 800 compounds. Linearity, imprecision, and limit
      of quantitation were established. In each analytical batch, low and high controls
      were included. RESULTS: All 18 urine specimens tested positive for methadone and
      EDDP. Several other compounds were also identified, including morphine, THC-COOH,
      benzoylecgonine, nicotine, some antidepressants, and neuroleptics. Methadone and
      EDDP were identified in exhaled breath from all 18 patients, with concentrations
      in the range 11-1470 and 29-818 pg per filter, respectively. In 13 cases, the
      ratio methadone/EDDP in exhaled breath was >1 (range 0.4-2.8). Except nicotine (n
      = 7), no other substance was detectable in exhaled breath. CONCLUSION: This study
      gives further support to the possibility of using exhaled breath as a new matrix
      to document exposure to drugs.

PMID- 26222874
TI  - Development of an ELISA-Based Competitive Binding Assay for the Analysis of Drug
      Concentration and Antidrug Antibody Levels in Patients Receiving Adalimumab or
      Infliximab.
AB  - BACKGROUND: There is increasing interest in measuring both drug and antidrug
      antibody (ADA) levels in patients receiving anti-tumor necrosis factor treatment
      as part of algorithms for guiding therapeutic strategies. Many of the current
      assays for ADA detection have limitations with respect to specificity,
      sensitivity, and/or laboratory requirements. Specific identification of ADA based
      on their inhibitory activity in a simple competitive binding assay remains
      problematic. The development of an enzyme-linked immunosorbent assay (ELISA)
      based method for detection of both drug and ADA in patients receiving either
      adalimumab or infliximab would widen availability of monitoring for these
      patients. METHODS: An ELISA for the specific detection of adalimumab and
      infliximab using widely available reagents was developed. A simple modification
      for the detection of ADA capable of competitively inhibiting the in vitro binding
      of drug to solid phase tumor necrosis factor was also developed. Drug and ADA
      levels were analyzed in patients with rheumatoid arthritis and inflammatory bowel
      disease. RESULTS: The ELISA specifically detected drug concentrations in patient
      sera with no evidence of positive or negative interference by rheumatoid factor
      positive control sera. A subset of those patients with low drug concentrations
      had detectable levels of ADA with inhibitory activity in a competitive binding
      assay. Spiking with both drugs confirmed the specificity of the ADA detected.
      CONCLUSIONS: A modified ELISA protocol can be used to for the detection of both
      drug concentrations and ADA in patients receiving either adalimumab or
      infliximab. The ELISA incorporates those features identified in the literature as
      important for the accurate analysis of these antibodies and uses laboratory
      facilities and reagents that are widely available. It therefore provides a
      relatively simple and low cost assay for therapeutic drug monitoring of
      inpatients receiving adalimumab or infliximab.

PMID- 26222875
TI  - Patient involvement in Europe--a comparative framework.
AB  - PURPOSE: The purpose of this paper is to provide and explain the model that
      underlies most of the research reported within this special issue on "Patient
      involvement in health care across Europe". DESIGN/METHODOLOGY/APPROACH: This
      introduction provides a literature review and a conceptual framework for the
      understanding of patient involvement and its potential development within health
      care across Europe. FINDINGS: Patient involvement can be characterised in terms
      of three ideal types: voice, choice and co-production. Policies for developing
      user involvement in healthcare can have disempowering as well as empowering
      consequences. The pattern of dissemination of user involvement across Europe
      varies in form and content largely due to path dependency. RESEARCH
      LIMITATIONS/IMPLICATIONS: The paper provides a template for future comparative
      research on user involvement in health care and one that could be extended to
      social care as well as other varieties of human services. This introduction and
      the special issue highlights the need for further comparative research in this
      area. ORIGINALITY/VALUE: The paper presents a robust model for comparative
      research. The findings may well be useful not only to researchers but also to
      policy makers and analysts.

PMID- 26222876
TI  - Patient involvement in quality management: rationale and current status.
AB  - PURPOSE: The purpose of this paper is to review how patient and public
      involvement (PPI) can contribute to quality improvement functions and describe
      the levels of PPI in quality improvement functions at hospital and departmental
      level in a sample of European hospitals. DESIGN/METHODOLOGY/APPROACH: Literature
      review and cross-sectional study. FINDINGS: PPI takes multiple forms in health
      care and there is not a single strategy or method that can be considered to
      reflect best practice. The literature reveals that PPI can serve important
      functions to support quality improvement efforts. In contrast, the assessment of
      actual PPI in quality improvement shows that PPI is low. RESEARCH
      LIMITATIONS/IMPLICATIONS: Findings are not representative of hospitals in the EU.
      PRACTICAL IMPLICATIONS: A diverse set of methods and tools that can be employed
      to realize PPI. Service providers should consider PPI at all stages, in
      particular in setting quality standards and criteria and in evaluating the
      results. ORIGINALITY/VALUE: Contextualization of empirical findings with case
      studies from the literature that inform further practice and research on PPI.

PMID- 26222877
TI  - Users' involvement in the Italian NHS: the role of associations and self-help
      groups.
AB  - PURPOSE: The purpose of the paper is to show the importance of considering
      patients' and citizens' associations for understanding users' involvement in
      health care systems. DESIGN/METHODOLOGY/APPROACH: The paper is based on both
      qualitative and quantitative data on Italy drawn from various sources (national
      statistics, own survey data, qualitative interviews). FINDINGS: Although the
      paper avoids an excessively positive view of the success and frequency of
      collective patients' participation, it nevertheless shows that the Italian
      National Health Care System (NHS) is undergoing important changes in this regard.
      Voice and co-production among patients, health care services and professionals
      have become more common and important also because of forms of collective action.
      Professionals themselves often belong to or promote such associations and groups.
      The Italian case also shows that voice and co-production tend frequently to merge
      into a single complex strategy where patients' requests go along with their
      direct involvement in health care provision. SOCIAL IMPLICATIONS: The study
      provides useful information for policy makers considering the implementation of
      policies that promote collective action in order to increase an active users'
      participation in health care. ORIGINALITY/VALUE: This is one of the limited
      number of Italian studies which investigates users' involvement in the NHS and
      collective action, thus adding knowledge to the limited research in this field.

PMID- 26222878
TI  - User involvement in assisted reproductive technologies: England and Portugal.
AB  - PURPOSE: The purpose of this paper is to compare user involvement in the case of
      assisted reproductive technologies in England and Portugal through the concepts
      of voice, choice and co-production, assessing the implications for user
      empowerment. DESIGN/METHODOLOGY/APPROACH: This qualitative study draws primarily
      on policy review and uses exploratory semi-structured interviews with key
      informants as a way of illustrating points. Data on the following themes was
      compared: voice (users' representativeness on licensing bodies and channels of
      communication between users and doctors); choice (funding and accessibility
      criteria; choice of fertility centres, doctors and level of care); and co
      production (criteria through which users actively engage with health
      professionals in planning the treatment). FINDINGS: Inter- and intra-healthcare
      systems variations between the two countries on choice and co-production were
      identified. Differences between funding and accessibility, regions, public and
      private sectors and attitudes towards doctor-patient relationship
      (paternalistic/partnership) were the key issues. Although consumer choice and
      indicators of co-production are evident in treatment pathways in both countries,
      user empowerment is not. This is limited by inequalities in accessibility
      criteria, dependence on doctors' individual perspectives and lack of genuine and
      formal hearing of citizens' voice. ORIGINALITY/VALUE: Enhancing users'
      involvement claims for individual and organizational cultures reflecting user
      centred values. Effective ways to incorporate users' knowledge in shared decision
      making and co-design are needed to empower patients and to improve the delivery
      of care.

PMID- 26222879
TI  - User involvement in Slovenian healthcare.
AB  - PURPOSE: The purpose of this paper is to report on current developments in user
      involvement in healthcare in Slovenia and to explore the issue from the macro-,
      mezzo- and micro-levels. DESIGN/METHODOLOGY/APPROACH: User involvement is first
      contextualised within history of the organisation of healthcare system, from its
      socialist past through to its post-transitional developments. Second, user
      involvement is tracked through an analysis of healthcare policies and legislation
      as well as at its institutional and organisational levels. Finally, user
      involvement practices are illustrated from the perspective of individual
      patients. A descriptive and exploratory case study design was employed, including
      a literature review, document analysis and qualitative thematic analysis of nine
      in-depth and four semi-structured interviews. FINDINGS: The findings reveal a
      complex and at times ambivalent picture in which user involvement is still not
      firmly embedded into the healthcare system, despite being generally accepted.
      ORIGINALITY/VALUE: No systematic qualitative research of patient involvement in
      Slovenia has previously been published. This research will establish a basis for
      further investigations of the topic.

PMID- 26222880
TI  - Patient involvement in Danish health care.
AB  - PURPOSE: The purpose of this paper is to investigate different types of patient
      involvement in Denmark, and to discuss the potential implications of pursuing
      several strategies for patient involvement simultaneously.
      DESIGN/METHODOLOGY/APPROACH: The paper presents a preliminary framework for
      analysis of patient involvement in health care. This framework is used to analyze
      key governance features of patient involvement in Denmark based on previous
      research papers and reports describing patient involvement in Danish health care.
      FINDINGS: Patient involvement is important in Denmark at the rhetorical level,
      and many policies and initiatives have been introduced. All three governance
      forms (voice, choice and co-production) are used. However, there are important
      barriers and limitations in translating the rhetoric into practice, and potential
      synergy and negative synergy effects can be identified when pursuing the
      strategies at the same time. RESEARCH LIMITATIONS/IMPLICATIONS: Because of the
      chosen research approach, the research results may lack generalizability.
      Therefore, researchers are encouraged to test the proposed framework further.
      PRACTICAL IMPLICATIONS: The paper includes implications for the development of
      patient involvement in health care. ORIGINALITY/VALUE: This paper fulfills a need
      to study different types of patient involvement and to develop a theoretical
      framework for characterizing and analyzing such involvement strategies.

PMID- 26222881
TI  - A comparative study of contemporary user involvement within healthcare systems
      across England, Poland and Slovenia.
AB  - PURPOSE: The purpose of this paper is to explore how healthcare-users' engagement
      is perceived, how it occurs and how these perceptions differ between three
      European countries: England, Poland and Slovenia, using the concepts of voice,
      choice and coproduction. DESIGN/METHODOLOGY/APPROACH: This comparative,
      qualitative study is based on a review of legal documents, academic literature
      and semi-structured interviews conducted in October and November 2011. A research
      sample consisted of 21 interviewees representing various stakeholders including
      healthcare-users, doctors and managers. Primary and secondary data were analysed
      using theoretical thematic analysis. Emerging themes were identified from the
      interviews and related to the indicators describing healthcare-users' involvement
      in the voice, choice and coproduction model. FINDINGS: Results of the comparative
      qualitative research suggest that the healthcare-users' influence is strongly
      grounded in England where the healthcare system and professionals are prepared to
      include healthcare-users in the decision-making process. In Slovenia, cultural
      development of healthcare-users' involvement seems to proceed the institutional
      development. In Poland, institutions are ready to involve healthcare-users in
      decision-making process although the cultural desirability of involving users
      among doctors and patients is lacking. ORIGINALITY/VALUE: The notion of user
      involvement is increasingly gaining importance and research attention, yet there
      is still little known about the way cultural, political, historical differences
      between various European countries influence it. This paper explores this little
      known area using the original approach of user involvement (Dent et al., 2011)
      with input from various stakeholders including patients, healthcare
      representatives and academics.

PMID- 26222882
TI  - Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis.
AB  - Recommender systems are highly vulnerable to shilling attacks, both by
      individuals and groups. Attackers who introduce biased ratings in order to affect
      recommendations, have been shown to negatively affect collaborative filtering
      (CF) algorithms. Previous research focuses only on the differences between
      genuine profiles and attack profiles, ignoring the group characteristics in
      attack profiles. In this paper, we study the use of statistical metrics to detect
      rating patterns of attackers and group characteristics in attack profiles.
      Another question is that most existing detecting methods are model specific. Two
      metrics, Rating Deviation from Mean Agreement (RDMA) and Degree of Similarity
      with Top Neighbors (DegSim), are used for analyzing rating patterns between
      malicious profiles and genuine profiles in attack models. Building upon this, we
      also propose and evaluate a detection structure called RD-TIA for detecting
      shilling attacks in recommender systems using a statistical approach. In order to
      detect more complicated attack models, we propose a novel metric called DegSim'
      based on DegSim. The experimental results show that our detection model based on
      target item analysis is an effective approach for detecting shilling attacks. 

PMID- 26222883
TI  - Cardiovascular disease (CVD) in Canadians with haemophilia: Age-Related CVD in
      Haemophilia Epidemiological Research (ARCHER study).
AB  - INTRODUCTION: Improvements in haemophilia care have increased life expectancy in
      persons with haemophilia (PWH). This ageing population presents clinicians with
      management challenges as they develop age-related comorbidities such as
      cardiovascular disease (CVD). AIMS: To assess the epidemiology of CVD risk
      factors and events in an ageing Canadian haemophilia population. METHODS: A
      retrospective, multicentre chart review was carried out at five Canadian
      Hemophilia Treatment Centres. PWH (A and B) >=35 years old were included and data
      were extracted on CVD risk factors and events. RESULTS: Data from 294 patients'
      charts were analysed including 222 (75.5%) patients with haemophilia A and 72
      (24.5%) patients with haemophilia B with a median age at end of follow-up of 54
      years (range = 36-90). Mean follow-up duration was 5.86 years. Cardiovascular
      risk factors were common: hypertension 31.3% (n = 90), diabetes mellitus 10.5% (n
      = 29), smoking 21.8% (n = 61), obesity 27.6% (n = 69), dyslipidaemia 22.4% (n =
      65), family history 8.5% (n = 24), antiretroviral therapy 12.2% (n = 36). There
      were 24 CVD events (8.2% of the population) with a median age at event of 63
      years (range = 46-83). Events consisted of coronary artery disease (CAD), 14;
      cerebrovascular disease, 4; and atrial fibrillation, 7. CAD was treated with
      coronary artery bypass grafting in three patients and percutaneous coronary
      intervention in nine patients. CVD events were complicated by six bleeding events
      (three minor and three major). CONCLUSION: Cardiovascular disease risk factors
      and events are relatively common in PWH. PWH can be safely treated for CVD events
      with similar procedures as the non-PWH populations, though specific clotting
      factor prophylaxis protocols are not well defined.

PMID- 26222885
TI  - Engineering nanoscale stem cell niche: direct stem cell behavior at cell-matrix
      interface.
AB  - Biophysical cues on the extracellular matrix (ECM) have proven to be significant
      regulators of stem cell behavior and evolution. Understanding the interplay of
      these cells and their extracellular microenvironment is critical to future tissue
      engineering and regenerative medicine, both of which require a means of
      controlled differentiation. Research suggests that nanotopography, which mimics
      the local, nanoscale, topographic cues within the stem cell niche, could be a way
      to achieve large-scale proliferation and control of stem cells in vitro. This
      Progress Report reviews the history and contemporary advancements of this
      technology, and pays special attention to nanotopographic fabrication methods and
      the effect of different nanoscale patterns on stem cell response. Finally, it
      outlines potential intracellular mechanisms behind this response. 

PMID- 26222884
TI  - Effects of Aged Stored Autologous Red Blood Cells on Human Endothelial Function.
AB  - RATIONALE: A major abnormality that characterizes the red cell "storage lesion"
      is increased hemolysis and reduced red cell lifespan after infusion. Low levels
      of intravascular hemolysis after transfusion of aged stored red cells disrupt
      nitric oxide (NO) bioavailabity, via accelerated NO scavenging reaction with cell
      free plasma hemoglobin. The degree of intravascular hemolysis post-transfusion
      and effects on endothelial-dependent vasodilation responses to acetylcholine have
      not been fully characterized in humans. OBJECTIVES: To evaluate the effects of
      blood aged to the limits of Food and Drug Administration-approved storage time on
      the human microcirculation and endothelial function. METHODS: Eighteen healthy
      individuals donated 1 U of leukopheresed red cells, divided and autologously
      transfused into the forearm brachial artery 5 and 42 days after blood donation.
      Blood samples were obtained from stored blood bag supernatants and the
      antecubital vein of the infusion arm. Forearm blood flow measurements were
      performed using strain-gauge plethysmography during transfusion, followed by
      testing of endothelium-dependent blood flow with increasing doses of
      intraarterial acetylcholine. MEASUREMENTS AND MAIN RESULTS: We demonstrate that
      aged stored blood has higher levels of arginase-1 and cell-free plasma
      hemoglobin. Compared with 5-day blood, the transfusion of 42-day packed red cells
      decreases acetylcholine-dependent forearm blood flows. Intravascular venous
      levels of arginase-1 and cell-free plasma hemoglobin increase immediately after
      red cell transfusion, with more significant increases observed after infusion of
      42-day-old blood. CONCLUSIONS: We demonstrate that the transfusion of blood at
      the limits of Food and Drug Administration-approved storage has a significant
      effect on the forearm circulation and impairs endothelial function. Clinical
      trial registered with www.clinicaltrials.gov (NCT 01137656).

PMID- 26222886
TI  - Adjuvant effect of B domain of staphyloccocal protein A displayed on the surface
      of hepatitis B virus capsid.
AB  - The hepatitis B virus (HBV) capsid-based recombinant particles, which display
      both major hydrophilic region of HBV surface antigen (HBV-MHR) and B domain of
      Staphylococcal protein A (SPAB ), were produced using Escherichia coli as
      expression host. SPAB was used as an adjuvant to elicit the immune response to
      HBV-MHR, and its adjuvant effect in the immunized mice was estimated with varying
      the position and amount of SPAB on the HBV capsid particles. Compared to the
      emulsified aluminum gel (alum gel) that is a currently commercialized vaccine
      adjuvant, SPAB caused the significantly higher level of anti-HBV immunoglobulin G
      (IgG) titer and seroconversion rate, and notably SPAB at the most surface-exposed
      position on the recombinant particle led to the highest immune response.
      Moreover, SPAB caused much lower ratio of IgG1 to IgG2a compared to alum gel,
      indicating that helper T-cell 1-mediated immune response (responsible for
      cytotoxic T-cell stimulation) is relatively more stimulated by SPAB , unlike alum
      gel that mainly stimulates helper T-cell 2-mediated immune response (responsible
      for B-cell stimulation). Although HBV-MHR and HBV capsid particle were used as
      proof-of-concept in this study, SPAB can be used as a highly effective adjuvant
      with other disease-specific antigens on the surface of other virus-like particles
      to produce various recombinant vaccines with high potency.

PMID- 26222888
TI  - Association of Heart Rate Turbulence With Arrhythmia Susceptibility and Heart
      Disease in Mice.
AB  - INTRODUCTION: Recent studies have demonstrated the feasibility of measuring heart
      rate turbulence (HRT) as a marker of baroreflex function in healthy mice. The aim
      of this investigation was to measure HRT in a mouse model with induced structural
      heart defects and to determine if there were threshold values of HRT for
      inducible ventricular tachycardias (VTs). METHODS AND RESULTS: HRT was measured
      during electrophysiological investigations 2 weeks after transverse aortic
      constriction (TAC, n = 13) or myocardial cryoinfarction (MCI, n = 14). Sham
      operated mice served as controls (n = 8 for TAC controls and n = 9 for MCI
      controls). Mice with heart disease lacked an early acceleration (turbulence onset
      [TO]) in heart rate after extrastimulus pacing (heart disease: 0.39% [0.19%
      0.59%] vs. all controls: -0.04% [-0.25-0.19%]; P < 0.01). At a cutoff value of
      >0.25%, TO could be used to classify mice with induced heart disease with a
      sensitivity of 64.0% and specificity of 88.2% (P < 0.01) but did not identify
      mice at higher risk of induced VTs. Animals that were susceptible to VTs (n = 8)
      had lower values for turbulence slope (TS) compared with noninducible mice (6.2
      milliseconds/beat [3.1-9.5 milliseconds/beat] vs. 10.1 milliseconds/beat [7.2
      14.2 milliseconds/beat]; P = 0.03). TS <7.8 milliseconds/beat identified mice
      with inducible VTs with a sensitivity of 75.0% and specificity of 75.8% (P =
      0.02). CONCLUSION: Measurement of HRT is feasible in mouse models with induced
      structural heart disease. More abnormal values for TO were found in the presence
      of structural heart disease but did not predict susceptibility to VTs. Decreased
      TS was associated with VTs induced by programmed stimulation.

PMID- 26222887
TI  - Mapping and Modelling the Geographical Distribution and Environmental Limits of
      Podoconiosis in Ethiopia.
AB  - BACKGROUND: Ethiopia is assumed to have the highest burden of podoconiosis
      globally, but the geographical distribution and environmental limits and
      correlates are yet to be fully investigated. In this paper we use data from a
      nationwide survey to address these issues. METHODOLOGY: Our analyses are based on
      data arising from the integrated mapping of podoconiosis and lymphatic filariasis
      (LF) conducted in 2013, supplemented by data from an earlier mapping of LF in
      western Ethiopia in 2008-2010. The integrated mapping used woreda (district)
      health offices' reports of podoconiosis and LF to guide selection of survey
      sites. A suite of environmental and climatic data and boosted regression tree
      (BRT) modelling was used to investigate environmental limits and predict the
      probability of podoconiosis occurrence. PRINCIPAL FINDINGS: Data were available
      for 141,238 individuals from 1,442 communities in 775 districts from all nine
      regional states and two city administrations of Ethiopia. In 41.9% of surveyed
      districts no cases of podoconiosis were identified, with all districts in Affar,
      Dire Dawa, Somali and Gambella regional states lacking the disease. The disease
      was most common, with lymphoedema positivity rate exceeding 5%, in the central
      highlands of Ethiopia, in Amhara, Oromia and Southern Nations, Nationalities and
      Peoples regional states. BRT modelling indicated that the probability of
      podoconiosis occurrence increased with increasing altitude, precipitation and
      silt fraction of soil and decreased with population density and clay content.
      Based on the BRT model, we estimate that in 2010, 34.9 (95% confidence interval
      [CI]: 20.2-51.7) million people (i.e. 43.8%; 95% CI: 25.3-64.8% of Ethiopia's
      national population) lived in areas environmentally suitable for the occurrence
      of podoconiosis. CONCLUSIONS: Podoconiosis is more widespread in Ethiopia than
      previously estimated, but occurs in distinct geographical regions that are tied
      to identifiable environmental factors. The resultant maps can be used to guide
      programme planning and implementation and estimate disease burden in Ethiopia.
      This work provides a framework with which the geographical limits of podoconiosis
      could be delineated at a continental scale.

PMID- 26222889
TI  - The Urochloa Foliar Blight and Collar Rot Pathogen Rhizoctonia solani AG-1 IA
      Emerged in South America Via a Host Shift from Rice.
AB  - The fungus Rhizoctonia solani anastomosis group (AG)-1 IA emerged in the early
      1990s as an important pathogen causing foliar blight and collar rot on pastures
      of the genus Urochloa (signalgrass) in South America. We tested the hypothesis
      that this pathogen emerged following a host shift or jump as a result of
      geographical overlapping of host species. The genetic structure of host and
      regional populations of R. solani AG-1 IA infecting signalgrass, rice, and
      soybean in Colombia and Brazil was analyzed using nine microsatellite loci in 350
      isolates to measure population differentiation and infer the pathogen
      reproductive system. Phylogeographical analyses based on the microsatellite loci
      and on three DNA sequence loci were used to infer historical migration patterns
      and test hypotheses about the origin of the current pathogen populations. Cross
      pathogenicity assays were conducted to measure the degree of host specialization
      in populations sampled from different hosts. The combined analyses indicate that
      the pathogen populations currently infecting Urochloa in Colombia and Brazil most
      likely originated from a population that originally infected rice. R. solani AG-1
      IA populations infecting Urochloa exhibit a mixed reproductive system including
      both sexual reproduction and long-distance dispersal of adapted clones, most
      likely on infected seed. The pathogen population on Urochloa has a genetic
      structure consistent with a high evolutionary potential and showed evidence for
      host specialization. 

PMID- 26222891
TI  - Erratum.

PMID- 26222890
TI  - A Qualitative Investigation of Health Care Professionals', Patients' and
      Partners' Views on Psychosocial Issues and Related Interventions for Couples
      Coping with Cancer.
AB  - INTRODUCTION: There is growing evidence that cancer affects couples as an
      interdependent system and that couple-based psychosocial interventions are
      efficacious in reducing distress and improving coping skills. However, adoption
      of a couples-focused approach into cancer care is limited. Previous research has
      shown that patients and partners hold differing views from health care
      professionals (HCPs) regarding their psychosocial needs, and HCPs from different
      disciplines also hold divergent views regarding couples' psychosocial needs. This
      study aimed to explore the perspectives of HCPs and couples on the provision of
      couple-focused psychosocial care in routine cancer services. METHODS: A
      qualitative study using semi-structured interviews was undertaken with 20 HCPs
      (medical oncologists, nurses, psycho-oncology professionals) and 20 couples where
      one member had been diagnosed with cancer (breast, prostate, head/neck, bowel,
      multiple myeloma). Interviews were analysed using the framework approach.
      RESULTS: Three core themes were identified: "How Do Couples Cope with Cancer?"
      emphasised the positive and negative coping strategies used by couples, and
      highlighted that partners perceived a lack of engagement by HCPs. "What Is Couple
      focused Psychosocial Care for People with Cancer?" described varying perspectives
      regarding the value of couple-focused psychosocial care and variation in the
      types of support couples need among HCPs and couples. Whereas most couples did
      not perceive a need for specialist couple-focused support and interventions, most
      HCPs felt couple-focused psychosocial care was necessary. "How Can Couple-Focused
      Psychosocial Care be Improved?" described couples' view of a need for better
      provision of information, and the importance of their relationship with oncology
      clinicians. HCPs identified a lack of confidence in responding to the emotional
      needs of couples, and barriers to providing psychosocial care, including
      challenges identifying distress (through screening) and referring distressed
      individuals/couples for specialist assessment. CONCLUSIONS: The three core themes
      revealed discrepancies about couple-focused psychosocial care between HCPs and
      couples, and HCPs from different professional backgrounds, and several barriers
      to the provision of psychosocial care for couples. Despite HCPs and couples
      acknowledging that a couple-focused approach to psycho-social support was
      potentially beneficial, the majority of couples did not feel they needed specific
      couple-focused interventions. These issues and recommendations for future
      research are discussed.

PMID- 26222893
TI  - Moxifloxacin: An Alternative to Ethambutol for the Treatment of Presumed Ocular
      Tuberculosis.
AB  - OBJECTIVE: To present moxifloxacin as an alternative treatment option to
      ethambutol in an anti-tubercular therapy (ATT) regime in patients with presumed
      ocular tuberculosis (TB). METHODS: We identified all cases in our hospital
      referred for treatment of presumed ocular TB between 2009 and 2013. Age, gender,
      ophthalmic examination, blood tests, treatment regimens, adverse drug reactions,
      and outcomes were collected and analyzed for the patients who had moxifloxacin as
      part of their ATT. RESULTS: Forty-three cases of presumed ocular TB were treated
      with moxifloxacin as a part of ATT. Mean age was 44.18 +/- 12.47 years; 62.8%
      were male. A response to treatment, with no evidence of disease recurrence, was
      seen in 72.1% of cases. Shortened ATT duration was associated with increased risk
      of treatment failure (p = 0.02, 95% CI: -0.77 to -0.00). CONCLUSIONS:
      Moxifloxacin can be considered as a safe and effective alternative to ethambutol
      for the treatment of presumed ocular TB.

PMID- 26222892
TI  - N-(2-Hydroxypropyl)methacrylamide Copolymer-Drug Conjugates for Combination
      Chemotherapy of Acute Myeloid Leukemia.
AB  - There is a need for new treatment strategies of acute myeloid leukemia (AML). In
      this study, four different drugs, including cytarabine, daunorubicin, GDC-0980,
      and JS-K, were investigated in vitro for the two-drug combinations treatment of
      AML. The results revealed that cytarabine and GDC-0980 had the strongest
      synergism. In addition, cell cycle analysis was conducted to investigate the
      effect of the different combinations on cell division. For future in vivo
      application, N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-cytarabine and
      GDC-0980 conjugates were synthesized, respectively. In vitro studies demonstrated
      that both conjugates had potent cytotoxicity and their combination also showed
      strong synergy, suggesting a potential chemotherapeutic strategy for future AML
      treatment. 

PMID- 26222894
TI  - Multifunctional Electrochemical Platforms Based on the Michael Addition/Schiff
      Base Reaction of Polydopamine Modified Reduced Graphene Oxide: Construction and
      Application.
AB  - In this paper, a new strategy for the construction of multifunctional
      electrochemical detection platforms based on the Michael addition/Schiff base
      reaction of polydopamine modified reduced graphene oxide was first proposed.
      Inspired by the mussel adhesion proteins, 3,4-dihydroxyphenylalanine (DA) was
      selected as a reducing agent to simultaneously reduce graphene oxide and self
      polymerize to obtain the polydopamine-reduced graphene oxide (PDA-rGO). The PDA
      rGO was then functionalized with thiols and amines by the reaction of thiol/amino
      groups with quinine groups of PDA-rGO via the Michael addition/Schiff base
      reaction. Several typical compounds containing thiol and/or amino groups such as
      1-[(4-amino)phenylethynyl] ferrocene (Fc-NH2), cysteine (cys), and glucose
      oxidase (GOx) were selected as the model molecules to anchor on the surface of
      PDA-rGO using the strategy for construction of multifunctional electrochemical
      platforms. The experiments revealed that the composite grafted with ferrocene
      derivative shows excellent catalysis activity toward many electroactive molecules
      and could be used for individual or simultaneous detection of dopamine
      hydrochloride (DA) and uric acid (UA), or hydroquinone (HQ) and catechol (CC),
      while, after grafting of cysteine on PDA-rGO, simultaneous discrimination
      detection of Pb(2+) and Cd(2+) was realized on the composite modified electrode.
      In addition, direct electron transfer of GOx can be observed when GOx-PDA-rGO was
      immobilized on glassy carbon electrode (GCE). When glucose was added into the
      system, the modified electrode showed excellent electric current response toward
      glucose. These results inferred that the proposed multifunctional electrochemical
      platforms could be simply, conveniently, and effectively regulated through
      changing the anchored recognition or reaction groups. This study would provide a
      versatile method to design more detection or biosensing platforms through a
      chemical reaction strategy in the future. 

PMID- 26222895
TI  - Membrane turnover and receptor trafficking in regenerating axons.
AB  - Peripheral axonal regeneration requires surface-expanding membrane addition. The
      continuous incorporation of new membranes into the axolemma allows the pushing
      force of elongating microtubules to drive axonal growth cones forwards. Hence, a
      constant supply of membranes and cytoskeletal building blocks is required, often
      for many weeks. In human peripheral nerves, axonal tips may be more than 1 m away
      from the neuronal cell body. Therefore, in the initial phase of regeneration,
      membranes are derived from pre-existing vesicles or synthesised locally. Only
      later stages of axonal regeneration are supported by membranes and proteins
      synthesised in neuronal cell bodies, considering that the fastest anterograde
      transport mechanisms deliver cargo at 20 cm/day. Whereas endocytosis and
      exocytosis of membrane vesicles are balanced in intact axons, membrane
      incorporation exceeds membrane retrieval during regeneration to compensate for
      the loss of membranes distal to the lesion site. Physiological membrane turnover
      rates will not be established before the completion of target reinnervation. In
      this review, the current knowledge on membrane traffic in axonal outgrowth is
      summarised, with a focus on endosomal vesicles as the providers of membranes and
      carriers of growth factor receptors required for initiating signalling pathways
      to promote the elongation and branching of regenerating axons in lesioned
      peripheral nerves.

PMID- 26222896
TI  - Skin Transfection Patterns and Expression Kinetics of Electroporation-Enhanced
      Plasmid Delivery Using the CELLECTRA-3P, a Portable Next-Generation Dermal
      Electroporation Device.
AB  - The CELLECTRA-3P dermal electroporation device (Inovio Pharmaceuticals, Plymouth
      Meeting, PA) has been evaluated in the clinic and shown to enhance the delivery
      of an influenza DNA vaccine. To understand the mechanism by which this device
      aids in enhancing the host immune response to DNA vaccines we investigated the
      expression kinetics and localization of a reporter plasmid (pGFP) delivered via
      the CELLECTRA-3P. Histological analysis revealed green fluorescent protein (GFP)
      expression as early as 1 hr posttreatment in the epidermal and dermal layers, and
      as early as 2 hr posttreatment in the subdermal layers. Immunofluorescence
      techniques identified keratinocytes, fibrocytes, dendritic-like cells,
      adipocytes, and myocytes as the principal cell populations transfected. We
      proceeded to demonstrate elicitation of robust host immune responses after
      plasmid DNA (pDNA) vaccination. In guinea pigs equivalent humoral (antibody
      binding titers) immune responses were observed between protocols using either
      CELLECTRA-3P or intramuscular electroporation to deliver the DNA vaccine. In
      nonhuman primates, robust interferon-gamma enzyme-linked immunospot and
      protective levels of hemagglutination inhibition titers after pDNA vaccination
      were observed in groups treated with the CELLECTRA-3P. In conclusion, these
      findings may assist in the future to design efficient, tolerable DNA vaccination
      strategies for the clinic. 

PMID- 26222897
TI  - In vitro investigation of Brazilian Cerrado plant extract activity against
      Plasmodium falciparum, Trypanosoma cruzi and T. brucei gambiense.
AB  - The threatened Brazilian Cerrado biome is an important biodiversity hotspot but
      still few explored that constitutes a potential reservoir of molecules to treat
      infectious diseases. We selected eight Cerrado plant species for screening
      against the erythrocytic stages of Plasmodium falciparum, human intracellular
      stages of Trypanosoma cruzi and bloodstream forms of T. brucei gambiense, and for
      their cytotoxicity upon the rat L6-myoblast cell line. Bioassays were performed
      with 37 hexane, ethyl acetate and ethanol extracts prepared from different plant
      organs. Activities against parasites were observed for 24 extracts: 9 with anti
      P. falciparum, 4 with anti-T. cruzi and 11 with anti-T. brucei gambiense
      activities. High anti-protozoal activity (IC50 values < 10 MUg/mL) without
      obvious cytotoxicity to L6 cells was observed for eight extracts from plants:
      Connarus suberosus, Blepharocalyx salicifolius, Psidium laruotteanum and Myrsine
      guianensis. Overall, studies of plant extracts will contribute to increase the
      biodiversity knowledge essential for Cerrado conservation and sustainable
      development. 

PMID- 26222898
TI  - National Health and Nutrition Examination Survey Biospecimen Program: NHANES III
      (1988-1994) and NHANES 1999-2014.
AB  - BACKGROUND: The National Health and Nutrition Examination Survey's 9NHANES)
      biospecimena program was formed to manage the collection of biospecimena
      (including serum, plasma, urine, and DNA) from NHANES cycles, the storage of
      biospecimens in NHANES biospecimens, accessing of biospecimens by researchers and
      the providing of resulting data to future researchers. Data from biospeceimen
      research can be combined with existing NHANES data. OBJECTIVE: This report
      provides background on the development of NHANES biorepositories and describes
      the collection, processing, and storing of biospecimens; ethical considerations
      and informed consent; and the proposal process for accessing biospecimens and
      resulting data. The number and types of biospecimens collected in each survey
      cycle from NHANES III (1988- 1994) through NHANES 1999-2014 are discussed so that
      researchers can understand what biospecimens are available if they are
      considering using NHANES biospecimens in their research.

PMID- 26222899
TI  - Presynaptic size of associational/commissural CA3 synapses is controlled by
      fibroblast growth factor 22 in adult mice.
AB  - Associational/commissural CA3-CA3 synapses define the recurrent CA3 network that
      generates the input to CA1 pyramidal neurons. We quantified the fine structure of
      excitatory synapses in the stratum radiatum of the CA3d area in adult wild type
      (WT) and fibroblast growth factor 22 knock-out (FGF22KO) mice by using serial 3D
      electron microscopy. WT excitatory CA3 synapses are rather small yet range 10
      fold in size. Spine size, however, was small and uniform and did not correlate
      with the size of the synaptic junction. To reveal mechanisms that regulate
      presynaptic structure, we investigated the role of FGF22, a target-derived signal
      specific for the distal part of area CA3 (CA3d). In adult FGF22KO mice,
      postsynaptic properties of associational CA3 synapses were unaltered.
      Presynaptically, the number of synaptic vesicles (SVs), the bouton volume, and
      the number of vesicles in axonal regions (the super pool) were reduced. This
      concurrent decrease suggests concerted control by FGF22 of presynaptic size. This
      hypothesis is supported by the finding that WT presynapses in the proximal part
      of area CA3 (CA3p) that do not receive FGF22 signaling in WT mice were smaller
      than presynapses in CA3d in WT but of comparable size in CA3d of FGF22KO mice.
      Docked SV density was decreased in CA1, CA3d, and CA3p in FGF22KO mice. Because
      CA1 and CA3p are not directly affected by the loss of FGF22, the smaller docked
      SV density may be an adaptation to activity changes in the CA3 network. Thus,
      docked SV density potentially is a long-term regulator for the synaptic release
      probability and/or the strength of short-term depression in vivo.

PMID- 26222900
TI  - The Flawed Reliance on Randomized Controlled Trials in Studies of HIV Behavioral
      Prevention Interventions for People Who Inject Drugs and Other Populations.
AB  - This article discusses ways in which randomized controlled trials do not
      accurately measure the impact of HIV behavioral interventions. This is because:
      1. Such trials measure the wrong outcomes. Behavior change may have little to do
      with changes in HIV incidence since behavior change in events between HIV
      concordant people have no impact on incidence. Even more important, the
      comparison of HIV incidence rates between study arms of individual-level RCTs
      does not measure the true outcome of interest-whether or not the intervention
      reduces HIV transmission at the community level. This is because this comparison
      cannot measure the extent to which the intervention stops transmission by HIV
      infected people in the study to those outside it. (And this is made even worse if
      HIV-infected are excluded from the evaluation of the intervention.) 2. There are
      potential harms implicit in most cognitively oriented behavioral interventions
      that are not measured in current practice and may not be measurable using RCTs.
      Intervention trials often reinforce norms and values of individual self
      protection. They rarely if ever measure whether doing this reduces community
      trust, solidarity, cohesion, organization, or activism in ways that might
      facilitate HIV transmission. 3. Many interventions are not best conceived of as
      interventions with individuals but rather with networks, cultures of risks, or
      communities. As such, randomizing individuals leads to effective interventions
      that diffuse protection through a community; but these are evaluated as
      ineffective because the changes diffuse to the control arm, which leads to
      systematic and erroneous reductions in the evaluated effectiveness as RCTs
      measure it. The paper ends by discussing research designs that are superior to
      individual-level RCTs at measuring whether an intervention reduces or increases
      new HIV transmission. 

PMID- 26222901
TI  - Rhodium(III)-catalyzed oxidative bicyclization of 4-arylbut-3-yn-1-amines with
      internal alkynes through C-H functionalization.
AB  - A new Rh(iii)-catalyzed oxidative bicyclization through C-H functionalization is
      presented. This reaction allows the selective assembly of diverse benzo[g]indoles
      from 4-arylbut-3-yn-1-amines and internal alkynes via a sequence of aromatic
      C(sp(2))-H functionalization, cyclodimerization and nucleophilic cyclization. 

PMID- 26222902
TI  - The impact of CCR5-Delta32 deletion on C-reactive protein levels and
      cardiovascular disease: Results from the Danish Blood Donor Study.
AB  - BACKGROUND AND PURPOSE: The C-C chemokine receptor 5-Delta32 deletion (CCR5
      Delta32) has been associated with lower levels of C-reactive protein (CRP), but
      the effect on cardiovascular diseases is uncertain. This study addresses the
      impact of CCR5-Delta32 on the risk of low-grade inflammation and hospitalization
      with cardiovascular diseases in a large cohort of blood donors. METHODS:
      Genotyping of 15,206 healthy participants from The Danish Blood Donor Study for
      CCR5-Delta32 was performed and combined with CRP measurements and questionnaire
      data. Cardiovascular disease diagnoses were identified by ICD-10 codes in the
      Danish National Patient Registry. RESULTS: CCR5-Delta32-carriers had a higher
      risk of hospitalization for cardiovascular diseases when compared with wild-type
      homozygotes (hazard ratio = 1.35, 95%-confidence interval: 1.00-1.87). CRP levels
      were unaffected by the CCR5-Delta32 deletion. CONCLUSION: In this cohort,
      carriers of the CCR5-Delta32 deletion had normal CRP levels but a borderline
      significant increased risk of cardiovascular diseases.

PMID- 26222903
TI  - Lipoprotein (a) levels are not associated with carotid plaques and carotid intima
      media thickness in statin-treated patients with familial hypercholesterolemia.
AB  - BACKGROUND: Lipoprotein (a), also called Lp(a), is a cardiovascular disease (CVD)
      risk factor. Statins do not lower Lp(a), this may at least partly explain
      residual CVD risk in statin-treated patients with familial hypercholesterolemia
      (FH). We investigated the association of Lp(a) levels with atherosclerosis in
      these patients. METHODS AND RESULTS: We performed ultrasonography in 191 statin
      treated FH patients (50% men; 48 +/- 15 years) to detect carotid plaques and
      determine carotid intima-media thickness (C-IMT). Patients with high versus low
      Lp(a) levels (<=0.3 g/L) had similar plaque prevalence (36 and 31%, p = 0.4) and
      C-IMT (0.59 +/- 0.12 and 0.59 +/- 0.13 mm, p = 0.8). Patients with and without
      plaques had similar Lp(a) levels (median 0.35 (IQR: 0.57) and 0.24 (0.64) g/L,
      respectively, p = 0.4). CONCLUSIONS: The Lp(a) levels were not associated with
      atherosclerosis in the carotid arteries of statin-treated FH patients. This
      suggests that adequate statin treatment delays carotid atherosclerosis in FH
      independently of Lp(a) levels.

PMID- 26222904
TI  - Simultaneous determination of ginsenoside Rb1, naringin, ginsenoside Rb2 and
      oridonin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study
      after oral administration of Weifuchun tablet.
AB  - A sensitive, specific and rapid liquid chromatography-mass spectrometry (LC-MS)
      method was developed and validated for analysis of ginsenoside Rb1, naringin,
      ginsenoside Rb2 and oridonin in rat plasma using sulfamethoxazole as an internal
      standard (IS). Separation was conducted out on an Agilent Eclipse XDB C18 column
      with liner gradient elution using acetonitrile (A) and 0.1% aqueous acetic acid
      (B). A tandem mass spectrometric detection was conducted using multiple reaction
      monitoring (MRM) via an electrospray ionization (ESI) source. A novel multi
      determination-periods program was executed to achieve a higher sensitivity by
      setting three scanning periods. All analytes exhibited good linearity within the
      concentration range (r>0.9973). The lower limits of quantitation (LLOQ) of
      ginsenoside Rb1, naringin, ginsenoside Rb2 and oridonin were 2.64, 4.32, 2.32 and
      1.56ng/mL, respectively. Intra-day and inter-day precisions of the investigated
      components exhibited an RSD within 8.3%, and the accuracy (RE) ranged from -8.6%
      to 6.0% at all quality control levels. The developed method was successfully
      applied to a pharmacokinetic study of ginsenoside Rb1, naringin, ginsenoside Rb2
      and oridonin in rats after oral administration of a Weifuchun tablet. 

PMID- 26222905
TI  - Inhibitory Effects of Highly Oxygenated Lanostane Derivatives from the Fungus
      Ganoderma lucidum on P-Glycoprotein and alpha-Glucosidase.
AB  - Twelve new highly oxygenated lanostane triterpenoids and nine known ganoderic
      acids were isolated from the fruiting body of Ganoderma lucidum. The new
      compounds were lanostane nortriterpenoids with 27 carbons (1-5 and 8), lanostane
      nor-triterpenoids with 25 carbons (6 and 7), and lanostane triterpenoids (9-12)
      based on multiple spectroscopic data analysis, including HRESIMS, 1D-NMR, 2D-NMR,
      and CD. Compounds 1-5 were identified as rare nor-lanostanoids that contain a
      17beta-pentatomic lactone ring. Compound 13, possessing a lactone ring, had been
      isolated previously. The P-glycoprotein (P-gp) inhibitory effects of compounds 1
      21 were evaluated at a concentration of 20 MUM using an adriamycin (ADM)
      resistant human breast adenocarcinoma cell line (MCF-7/ADR). Compounds 1, 5, 18,
      and 20 and verapamil increased the accumulation of ADM in MCF-7/ADR cells
      approximately 3-fold when compared with the negative control. These data support
      the significant P-glycoprotein inhibitory activities of compounds 1, 5, 18, and
      20. In silico docking analysis suggested these compounds had similar P-gp
      recognition mechanisms compared with those of verapamil (a classical inhibitor).
      Furthermore, in an in vitro bioassay, compounds 2, 4, 5, 6, and 18 showed
      moderate inhibitory effects against alpha-glucosidase compared with those of the
      positive control acarbose. 

PMID- 26222907
TI  - Differences in rheotactic responses contribute to divergent habitat use between
      parapatric lake and stream threespine stickleback.
AB  - Migration among populations is widely thought to undermine adaptive divergence,
      assuming gene flow arises from random movement of individuals. If individuals
      instead differ in dispersal behavior, phenotype-dependent dispersal can reduce
      the effective rate of gene flow or even facilitate divergence. For example,
      parapatric populations of lake and stream stickleback tend to actively avoid
      dispersing into the adjoining habitat. However, the behavioral basis of this
      nonrandom dispersal was previously unknown. Here, we show that lake and stream
      stickleback exhibit divergent rheotactic responses (behavioral response to
      currents). During the breeding season, wild-caught inlet stream stickleback were
      better than lake fish at maintaining position in currents, faced upstream more,
      and spent more time in low-current areas. As a result, stream fish expended
      significantly less energy in currents than did lake fish. These divergent
      rheotactic responses likely contribute to divergent habitat use by lake and
      stream stickleback. Although rheotactic differences were absent in nonbreeding
      fish, divergent behavior of breeding-season fish may suffice for assortative
      mating by breeding location. The resulting reproductive isolation between lake
      and stream fish may explain the fine-scale evolutionary differentiation in
      parapatric stickleback populations. 

PMID- 26222906
TI  - Long-Term Diabetes Mellitus Is Associated with an Increased Risk of Pancreatic
      Cancer: A Meta-Analysis.
AB  - PURPOSE: Previous studies have shown a bidirectional relationship between
      diabetes and pancreatic cancer (PC). In particular, new-onset diabetes might be
      induced by PC, and people with long-term diabetes might be at increased risk for
      the development of PC. The purpose of our study was to examine whether long-term
      diabetes represented an independent risk factor for PC development. METHODOLOGY:
      A literature search was performed by searching electronic databases for studies
      published before July 1, 2014, and relative risks (RRs) and corresponding 95%
      confidence intervals (CIs) were calculated. Data pertaining to diabetes were
      recorded at both individual and study levels, with RRs calculated separately to
      analyze the relationship between the duration of diabetes and the development of
      PC. RESULTS: Forty-four studies were included in this meta-analysis, including 18
      studies with a case-control design, 5 with a nested case-control design and 21
      with a cohort design. The overall summary estimate for the relationship between
      the population with a duration of diabetes >=2 years and PC was 1.64 (1.52-1.78).
      The pooled RR (95% CI) of PC for the population with a duration of diabetes >=5
      years was 1.58 (1.42-1.75). For the population with a duration of diabetes >=10
      years, the RR (95% CI) of PC was 1.50 (1.28-1.75). CONCLUSIONS: Our study
      suggests that long-term diabetes mellitus is associated with an increased risk of
      PC. However, the level of risk is negatively correlated with increasing diabetes
      mellitus duration.

PMID- 26222908
TI  - Muscular Arrangement and Muscle Attachment Sites in the Cervical Region of the
      American Barn Owl (Tyto furcata pratincola).
AB  - Owls have the largest head rotation capability amongst vertebrates. Anatomical
      knowledge of the cervical region is needed to understand the mechanics of these
      extreme head movements. While data on the morphology of the cervical vertebrae of
      the barn owl have been provided, this study is aimed to provide an extensive
      description of the muscle arrangement and the attachment sites of the muscles on
      the owl's head-neck region. The major cervical muscles were identified by gross
      dissection of cadavers of the American barn owl (Tyto furcata pratincola), and
      their origin, courses, and insertion were traced. In the head-neck region nine
      superficial larger cervical muscles of the craniocervical, dorsal and ventral
      subsystems were selected for analysis, and the muscle attachment sites were
      illustrated in digital models of the skull and cervical vertebrae of the same
      species as well as visualised in a two-dimensional sketch. In addition, fibre
      orientation and lengths of the muscles and the nature (fleshy or tendinous) of
      the attachment sites were determined. Myological data from this study were
      combined with osteological data of the same species. This improved the anatomical
      description of the cervical region of this species. The myological description
      provided in this study is to our best knowledge the most detailed documentation
      of the cervical muscles in a strigiform species presented so far. Our results
      show useful information for researchers in the field of functional anatomy,
      biomechanical modelling and for evolutionary and comparative studies. 

PMID- 26222909
TI  - Advanced Hepatocellular Carcinoma: Perfusion Computed Tomography-Based Kinetic
      Parameter as a Prognostic Biomarker for Prediction of Patient Survival.
AB  - OBJECTIVE: The aim of this study was to find prognostic biomarkers in perfusion
      computed tomography (PCT)-based kinetic parameters for advanced hepatocellular
      carcinoma (HCC) treated with antiangiogenic chemotherapy. METHODS: Twenty-two
      patients with advanced HCC underwent PCT imaging and subsequently received
      bevacizumab in combination with gemcitabine and oxaliplatin. Pretreatment PCT
      data within advanced HCC were analyzed using the Tofts-Kety, 2-compartment
      exchange, adiabatic approximation to the tissue homogeneity (AATH), and
      distributed parameter models. Blood flow, blood volume, extraction fraction (E),
      and other 3 parameters were calculated. Kinetic parameters in each model were
      evaluated with 1-year survival discrimination using Kaplan-Meier analysis and
      with overall survival using univariate Cox regression analysis. RESULTS: Only the
      AATH model-derived E was statistically significantly prognostic for 1-year
      survival. The increased AATH model-derived E was significantly associated with
      longer overall survival (P = 0.005). CONCLUSIONS: The AATH model-derived E was an
      effective prognostic biomarker for advanced HCC.

PMID- 26222910
TI  - Increasing access to healthful foods: a qualitative study with residents of low
      income communities.
AB  - BACKGROUND: Inadequate access to healthful foods has been identified as a
      significant barrier to healthful dietary behaviors among individuals who live in
      low-income communities. The purpose of this study was to gather low-income
      community members' opinions about their food purchasing choices and their
      perceptions of the most effective ways to increase access to healthful foods in
      their communities. METHODS: Spanish and English focus groups were conducted in
      low-income, ethnically-diverse communities. Participants were asked about their
      knowledge, factors influencing their food purchasing decisions, and their
      perceptions regarding solutions to increase access to healthful foods. RESULTS: A
      total of 148 people participated in 13 focus groups. The majority of participants
      were female and ethnically diverse (63% Hispanic, 17% African American, 16%
      Caucasian, and 4% "other"). More than 75% of the participants reported making
      less than $1999 USD per month. Participants reported high levels of knowledge and
      preference for healthful foods. The most important barriers influencing healthful
      shopping behaviors included high price of healthful food, inadequate geographical
      access to healthful food, poor quality of available healthful food, and lack of
      overall quality of the proximate retail stores. Suggested solutions to inadequate
      access included placement of new chain supermarkets in their communities.
      Strategies implemented in convenience stores were not seen as effective. Farmers'
      markets, with specific stipulations, and community gardens were regarded as
      beneficial supplementary solutions. CONCLUSION: The results from the focus groups
      provide important input from a needs assessment perspective from the community,
      identify gaps in access, and offer potential effective solutions to provide
      direction for the future.

PMID- 26222911
TI  - Interactions between alphav-Integrin and HER2 and Their Role in the Invasive
      Phenotype of Breast Cancer Cells In Vitro and in Rat Brain.
AB  - BACKGROUND: We tested the hypothesis that alphav-integrin and the human epidermal
      growth factor receptor type 2 (HER2) interact with each other in brain trophic
      metastatic breast cancer cells and influence their invasive phenotype. METHODS:
      Clones of MDA-MB231BR human breast cancer cells with stable knock down of alphav
      integrin in combination with high or low levels of HER2 were created. The
      interactions of these two proteins and their combined effect on cell migration
      and invasion were investigated in vitro and in vivo. RESULTS: Knockdown of alphav
      integrin in MDA-MB231BR clones altered the actin cytoskeleton and cell
      morphology. HER2 co-precipitated with alphav-integrin in three breast cancer cell
      lines in vitro, suggesting they complex in cells. Knockdown of alphav-integrin
      altered HER2 localization from its normal membrane position to a predominantly
      lysosomal localization. When alphav-integrin expression was decreased by 69-93%
      in HER2-expressing cells, cellular motility was significantly reduced. Deficiency
      of both alphav-integrin and HER2 decreased cellular migration and invasion by
      almost 90% compared to cells expressing both proteins (P<0.01). After
      intracerebral inoculation, cells expressing high levels of both alphav-integrin
      and HER2 showed a diffusely infiltrative tumor phenotype, while cells deficient
      in alphav-integrin and/or HER2 showed a compact tumor growth phenotype. In the
      alphav-integrin positive/HER2 positive tumors, infiltrative growth was 57.2 +/-
      19% of tumor volume, compared to only 5.8 +/- 6.1% infiltration in the double
      deficient tumor cells. CONCLUSIONS: alphav-integrin interacts with HER2 in breast
      cancer cells and may regulate HER2 localization. The combined impacts of alphav
      integrin and HER2 influence the invasive phenotype of breast cancer cells.
      Targeting alphav-integrin in HER2-positive breast cancer may slow growth and
      decrease infiltration in the normal brain.

PMID- 26222912
TI  - Deficiency of FHL2 attenuates airway inflammation in mice and genetic variation
      associates with human bronchial hyper-responsiveness.
AB  - BACKGROUND: Asthma is an inflammatory disease that involves airway hyper
      responsiveness and mucus hypersecretion. The LIM-only protein FHL2 is a crucial
      modulator of multiple signal transduction pathways and functions as a scaffold in
      specific protein-protein interactions. OBJECTIVE: We sought to investigate the
      role of FHL2 in airway inflammation. METHODS: Allergic airway inflammation was
      induced in WT and FHL2-knock out (FHL2-KO) mice with ovalbumin (OVA). Lung
      tissue, bronchoalveolar lavage fluid (BALF) and draining lymph node cells were
      analysed for inflammation. FHL2 loss and gain of function studies were performed
      in lung epithelial cells. RESULTS: FHL2-deficient mice challenged with OVA show
      significantly reduced airway inflammation as evidenced by reduced infiltration of
      inflammatory cells including eosinophils, dendritic cells, B cells and T cells.
      Furthermore, mucus production was decreased in FHL2-KO mice. In BALF, the levels
      of IL-5, IL-13, eotaxin-1 and eotaxin-2 were significantly lower in FHL2-KO mice.
      In addition, draining lymph node cells from FHL2-KO mice show reduced levels of
      IL-5 and IL-13. Consistent with this, OVA-specific serum IgG and IgE levels were
      reduced in FHL2-KO mice. We also found that phosphorylation of ERK1/2 is markedly
      attenuated in FHL2-KO lung. Knock-down of FHL2 in human lung epithelial cells
      resulted in a striking decrease in ERK1/2 phosphorylation and mRNA levels of
      inflammatory cytokines and MUC5AC, whereas FHL2 overexpression exhibited opposite
      effects. Finally, the SNP rs4851765 shows an association with the severity of
      bronchial hyper-responsiveness. CONCLUSION: These results highlight functional
      involvement of FHL2 in airway inflammation and identify FHL2 as a novel gene
      associated with asthma severity in human.

PMID- 26222913
TI  - Global expression profiling reveals shared and distinct transcript signatures in
      arrested act2(-) and CDPK4(-) Plasmodium berghei gametocytes.
AB  - Gametocytogenesis and gametogenesis in malaria parasites are complex processes of
      cell differentiation and development likely involving many gene products.
      Gametocytes develop in the blood of the vertebrate host but mature gametocytes
      are not activated until taken up by the mosquito vector. Several distinct mutants
      have been described that block gametogenesis but the detailed molecular causes
      for the mutant phenotypes are not understood. To investigate whether a block in
      gametogenesis also results in a changed transcriptional profile we studied two
      gene deletions mutants; act2(-) lacking stage-specific actin II and CDPK4(-)
      lacking calcium-dependent protein kinase 4. Whole genome microarray analysis was
      performed from RNA of mature gametocytes to compare the transcriptomes of the
      mutants with wild-type Plasmodium berghei. The microarray analysis identified
      ~12% of all genes being differentially expressed in either or both mutants
      compared to normal gametocytes, as defined by at least two-fold change in
      transcript abundance. A large proportion of the differentially expressed genes
      overlapped in the two mutants, consistent with a related outcome of gametocyte
      arrest. Distinct profiles in each mutant were also observed. Among the down
      regulated genes were thioredoxin 2 and members of the merozoite surface protein 7
      family. Generation and characterization of a msp7(-)/mspr1(-)/mspr2(-) triple
      mutant and re-analysis of trx2(-) parasites revealed no impairment of life cycle
      progression. Together, our analysis provides a resource for molecular signatures
      of Plasmodium berghei gametogenesis and exemplifies the potential of expression
      profiling of distinct genetically arrested parasites. 

PMID- 26222914
TI  - Generation of an aquaglyceroporin AQP1 null mutant in Leishmania major.
AB  - The Leishmania aquaglyceroporin AQP1 plays an important physiological role in
      water and uncharged polar solutes transport, volume regulation, osmotaxis, and is
      a key determinant of antimony resistance. By targeted gene disruption, we
      generated a Leishmania major promastigote AQP1 null mutant. This required several
      attempts but a chromosomal null AQP1 mutant was obtained by loss of
      heterozygosity in the presence of a rescue plasmid encoding AQP1. Growth in the
      absence of selection led to the loss of the rescuing plasmid, indicating that
      AQP1 is not essential for Leishmania viability. The AQP1-null mutant was
      resistant to antimonyl tartrate (SbIII) and arsenite (AsIII) due to a decrease
      import of these metalloids. It also exhibited alterations in its osmoregulation
      abilities compared with wild-type cells. This is the first report of the
      generation of a genetic AQP1 null mutant in Leishmania parasite, confirming its
      physiological function and role in resistance to antimonials, the therapeutic
      mainstay against Leishmania. 

PMID- 26222915
TI  - Clinical Study of Allogeneic Graft Reconstruction for Sternum Tumor.
AB  - OBJECTIVES: This paper aimed to study the feasibility, the surgical methodology,
      and technique for reconstruction using allogeneic sternal graft after sternum
      tumor resection. MATERIALS AND METHODS: Three patients (2 men and 1 woman, aged
      19, 44, and 52) with primary sternum malignant tumor were admitted from January
      2008 to December 2010 to the Second Hospital of Shandong University, Jinan,
      China. We conducted subtotal resection of the sternum and simultaneous
      reconstruction with allogeneic sternal graft. Allogeneic sternum was frozen
      beforehand; the scope of removal was 2 cm away from the lesion. Transplanted
      allogeneic sternum was fixed using steel wire and residual cavity was filled with
      the greater omentum. RESULTS: Three patients recovered without major complication
      and were discharged from the hospital with successful operation and satisfactory
      results. They were followed-up for 6 months to 2 years, no tumor relapse or any
      obvious rejection were found. CONCLUSIONS: The freezing allogeneic sternum can be
      used as a substitute for reconstruction after sternum tumor resection.

PMID- 26222917
TI  - Vascular Endothelial Growth Factor Peptide Ligands Explored by Competition Assay
      and Isothermal Titration Calorimetry.
AB  - The v114* cyclic peptide has been identified as a tight vascular endothelial
      growth factor (VEGF) ligand. Here we report on the use of isothermal titration
      calorimetry (ITC), 96-well plate competition assay, and circular dichroism (CD)
      to explore the binding determinants of a new set of related peptides. Anti-VEGF
      antibodies are currently used in the clinic for regulating angiogenesis in cancer
      and age-related macular degeneration treatment. In this context, our aim is to
      develop smaller molecular entities with high affinity for the growth factor by a
      structure activity relationship approach. The cyclic disulfide peptide v114* was
      modified in several ways, including truncation, substitution, and variation of
      the size and nature of the cycle. The results indicated that truncation or
      substitution of the four N-terminal amino acids did not cause severe loss in
      affinity, allowing potential peptide labeling. Increase of the cycle size or
      substitution of the disulfide bridge with a thioether linkage drastically
      decreased the affinity, due to an enthalpy penalty. The leucine C-terminal
      residue positively contributed to affinity. Cysteine N-terminal acetylation
      induced favorable DeltaDeltaG degrees  and DeltaDeltaH degrees  of binding, which
      correlated with free peptide CD spectra changes. We also propose a biochemical
      model to extrapolate Ki from IC50 values measured in the displacement assay.
      These calculated Ki correlate well with the Kd values determined by extensive
      direct and reverse ITC measurements. 

PMID- 26222916
TI  - Substituting Potassium Iodide for Methimazole as the Treatment for Graves'
      Disease During the First Trimester May Reduce the Incidence of Congenital
      Anomalies: A Retrospective Study at a Single Medical Institution in Japan.
AB  - BACKGROUND: To control hyperthyroidism due to Graves' disease, antithyroid drugs
      should be administered. Several studies have shown that exposure to methimazole
      (MMI) during the first trimester of pregnancy increases the incidence of specific
      congenital anomalies that are collectively referred to as MMI embryopathy.
      Congenital anomalies associated with exposure to propylthiouracil (PTU) have also
      recently been reported. METHODS: This study investigated whether substituting
      potassium iodide (KI) for MMI in the first trimester would result in a lower
      incidence of major congenital anomalies than continuing treatment with MMI alone.
      The cases of 283 women with Graves' disease (GD) were reviewed whose treatment
      was switched from MMI to KI in the first trimester (iodine group), as well as the
      cases of 1333 patients treated with MMI alone (MMI group) for comparison. Another
      major outcome of interest was the incidence of neonatal thyroid dysfunction. The
      subjects of the analysis of major congenital anomalies and neonatal thyroid
      dysfunction were live-born infants. RESULTS: The incidence of major anomalies was
      4/260 (1.53%) in the iodine group, which was significantly lower than the
      incidence of 47/1134 (4.14%) in the MMI group. Two neonates in the iodine group
      had anomalies consistent with MMI embryopathy (0.8%), as opposed to 18 neonates
      in the MMI group (1.6%). None of the neonates exposed to KI had thyroid
      dysfunction or goiter. CONCLUSIONS: Substituting KI for MMI as a means of
      controlling hyperthyroidism in GD patients during the first trimester may reduce
      the incidence of congenital anomalies, at least in iodine-sufficient regions.

PMID- 26222918
TI  - Domino reactions of diazodicarbonyl compounds with alpha,beta-unsaturated delta
      amino esters: a convenient way towards 2-oxopiperidines, dihydropyridinones and
      isoquinolinediones.
AB  - Thermal decomposition of a series of diazodicarbonyl compounds in the presence of
      alpha,beta-unsaturated delta-amino esters and sodium hydride gives rise to a
      variety of nitrogenous heterocycles. The direction of these processes is highly
      dependent on the structure of the initial reagents giving rise to the formation
      of multi-functionalized 2-oxopiperidines, 5,6-dihydropyridin-2(1H)-ones or
      tetrahydroisoquinoline-1,6(2H,8aH)-diones. The reactions occur in domino
      processes involving the Wolff rearrangement of diazocarbonyl compounds, NaH
      catalyzed anti-stereoselective intramolecular Michael addition to the alpha,beta
      unsaturated system of amino esters, and in some cases also cycloelimination and
      intramolecular Claisen condensation of the initial products formed. 

PMID- 26222919
TI  - On Deployment and Military Suicide Risk.

PMID- 26222920
TI  - Prognostic Factors for Long-Term Survival in Patients with Renal-Cell Carcinoma
      After Radiofrequency Ablation.
AB  - PURPOSE: To assess the long-term survival and prognostic factors in patients with
      renal-cell carcinoma (RCC) who were treated with radiofrequency ablation (RFA).
      PATIENTS AND METHODS: A retrospective review of the records of all patients who
      underwent RFA of biopsy-proven RCC from February 2006 to December 2010 was
      performed in our institution. Univariate and multivariate analyses were used to
      evaluate the prognostic factors for long-term survival after RFA. RESULTS: RFA
      was performed in 122 patients (102 men, 20 women) with preoperative imaging
      available. Mean patient age was 58.5 years (standard deviation [SD]: 14.5), and
      mean tumor size was 3.4 cm (SD: 1.1). Tumor stage was T1a 93 (76.2%) or T1b 29
      (23.8%). The mean follow-up period for RFA was 64.9 months (+/-11.6) (range 9-83
      mos). In total, 5-year cancer-specific survival, 5-year disease-free survival
      (DFS), 5-year recurrence-free survival (RFS), 5-year metastasis-free survival,
      and 5-year overall survival (OS) of this cohort was 98.3%, 90.8%, 94.2%, 99.2%,
      and 98.4%, respectively. In comparison with patients in >3 cm group, patients in
      <=3 cm group had better 5-year DFS (P = 0.009), 5-year OS (P = 0.036) and 5-year
      RFS (P = 0.011). Age and tumor size affected survival rates significantly at
      univariate analysis (P = 0.031, P = 0.033). Only tumor size was shown to have
      independent prognostic value in multivariate analysis (P = 0.034). CONCLUSION: In
      appropriately selected patients, RFA is an effective treatment option that
      provides comparable long-term survival. With use of RFA, there is a high
      probability of long-term survival of patients with small tumor size.

PMID- 26222921
TI  - Thermo-responsive and aqueous dispersible ZnO/PNIPAM core/shell nanoparticles.
AB  - In this work, we developed a new process to covalently graft a thermoresponsive
      polymer on the surface of fluorescent nanocrystals in order to synthesize
      materials that combine both responsive and fluorescent properties. For the first
      time, poly(N-isopropylacrylamide) (PNIPAM) was grown by activator regenerated by
      electron transfer-atom transfer radical polymerization (ARGET-ATRP) from ZnO
      quantum dots (QDs) by surface-initiated polymerization. This process allowed the
      formation of fluorescent and responsive ZnO/PNIPAM core/shell QDs while only
      requiring the use of a ppm amount of copper for the synthesis. The influence of
      the nature of the silanized layer and the polymerization time on the properties
      of the final nanomaterials were investigated. Results clearly evidence that both
      the PNIPAM layer thickness and the temperature affected the luminescence
      properties of the core/shell nanoparticles, but also that the PNIPAM layer, when
      it is thick enough, could stabilize the QDs' optical properties. 

PMID- 26222922
TI  - Eldercare work, migrant care workers, affective care and subjective proximity.
AB  - OBJECTIVES: To document and explore the experience of migrant care workers
      providing health and social care to the elderly in institutional care settings
      and in the homes of the elderly in the community in New Zealand with a particular
      focus on the affective components of care work. DESIGN: This qualitative study
      involved conducting face-to-face, open-ended, semi-structured interviews with 29
      migrant care workers in the eldercare sector in the cities of Auckland and
      Wellington, New Zealand. Participants were recruited through various agencies
      focusing on aged care and engaged with migrant eldercare workers and snowballing
      through participant referral. Sample size was determined when saturation was
      reached. The interviews were audio recorded, transcribed verbatim, themes were
      identified and then analysed drawing on a body of theoretical work in the fields
      of emotional anthropology and moral geography and the international empirical
      literature addressing migrant eldercare workers. RESULTS: As with the
      international research in this field we found that these workers were vulnerable
      to exploitation, the workforce is largely feminised and stereotypical
      understandings of racial groups and national characteristics informed recruitment
      and the workplace experience. Here attributing gradients of affect to particular
      migrant groups in the workforce was the main mechanism employed to establish
      worker worth and difference. Identifying with these gradients of affect enabled
      these eldercare workers to demonstrate that they met the moral and ethical
      requirements of permanent residency and ultimately citizenship. Eldercare workers
      in the home were vulnerable to 'blurred emotional boundaries' and care recipient
      demand for greater emotional commitment. The migrant eldercare workers in this
      study all shared vulnerable residential status and many feared they would never
      obtain permanent residency or citizenship. All had family who remained in the
      Philippines and towards whom they had an obligation to substitute care support.
      CONCLUSION: Central to understanding how this labour force issue is experienced
      by both caregivers and the elderly is the notion of subjective proximity and how
      emotional and moral trajectories serve to mediate the connection between the
      eldercare worker and workplace, the Filipino migrant eldercare relationship with
      employers, agencies and institutions; and, the transnational nature of this
      mobility and social and actual citizenship.

PMID- 26222923
TI  - Caffeine dimerization: effects of sugar, salts, and water structure.
AB  - Sugars and salts strongly affect the dimerization of caffeine in water. Such a
      change of dimerization, considered to be crucial for bitter taste suppression,
      has long been rationalized by the change of "water structure" induced by the
      additives; "kosmotropic" (water structure enhancing) salts and sugars promote
      dimerization, whereas "chaotropic" (water structure breaking) salts suppress
      dimerization. Based on statistical thermodynamics, here we challenge this
      consensus; we combine the rigorous Kirkwood-Buff theory of solution with the
      classical isodesmic model of caffeine association. Instead of the change of water
      structure, we show that the enhancement of caffeine dimerization is due to the
      exclusion of additives from caffeine, and that the weakening of dimerization is
      due to the binding of additives on caffeine. 

PMID- 26222928
TI  - Editorial: current strategies in advanced renal cell carcinoma.

PMID- 26222929
TI  - Imaging muscle-invasive and metastatic urothelial carcinoma.
AB  - PURPOSE OF REVIEW: Muscle-invasive bladder cancer (MIBC) comprises approximately
      one-third of bladder cancers and is associated with significant morbidity and
      mortality. Accurate staging of bladder cancer is essential because of
      significantly different treatment options and the consequences of inaccurate
      staging. The current recommended method for staging is transurethral resection of
      the bladder tumor followed by contrast-enhanced computed tomography (CT). In this
      review, we discuss cross-sectional imaging approaches used to assess local,
      nodal, and distant metastases in MIBC. RECENT FINDINGS: Determining the most
      accurate imaging method for staging MIBC is a contentious issue. CT with contrast
      is a practical approach; however, there is potential for understaging of small
      lymph nodes or foci of metastasis. Multiparametric MRI is emerging as the imaging
      modality of choice in tumor staging, with a reported accuracy of more than 90%.
      Locoregional lymph node metastasis can also be accurately evaluated using
      functional MRI and specific contrast agents with paramagnetic characteristics.
      PET/CT with conventional radiotracers is a common imaging modality for staging
      distant metastases. SUMMARY: Conventional imaging methods for evaluating MIBC are
      of limited use. However, recent advances in molecular imaging, targeted contrast
      agents, and functional MRI have shown promising results for the staging of
      bladder cancer.

PMID- 26222930
TI  - Dietary and non-dietary correlates of gastrointestinal distress during the cycle
      and run of a triathlon.
AB  - The purpose of this investigation was to assess whether pre-race dietary and non
      dietary factors were associated with gastrointestinal (GI) distress during the
      cycle and run of a 70.3-mile triathlon. Fifty three participants recorded dietary
      details the day before and morning of the triathlon and retrospectively reported
      GI symptoms from the cycle and run. Occurrence and severity of nausea,
      regurgitation and fullness were combined into an upper GI (UGI) category, while
      lower abdominal cramps, flatulence and urge to defecate were combined into a
      lower GI (LGI) category. Spearman's rho coefficients were used to examine whether
      UGI and LGI were associated with: (1) pre-race diet (kilocalories, carbohydrate,
      fibre, fat, protein, caffeine); and (2) non-dietary factors (age, body mass
      index, experience, weight change, GI distress history, finishing time). Of non
      dietary factors, only a history of GI distress showed significant associations
      with GI symptoms during the triathlon (rho = .32-.36; P < .05). Morning
      kilocalorie (rho = .28, P = .04) and carbohydrate (rho = .36, P < .01) intakes
      were modestly, positively associated with UGI during the cycle, while morning
      caffeine intake (rho = .30, P = .03) showed a modest positive association with
      LGI during the run. The associations between diet and GI distress variables
      remained significant after adjusting for non-dietary factors. Competitors of 70.3
      mile triathlons should carefully weigh the benefits of higher race-morning
      energy, carbohydrate and caffeine intakes against their potential to increase GI
      distress. 

PMID- 26222931
TI  - Choosing the Optimal Rigid Receptor for Docking and Scoring in the CSAR 2013/2014
      Experiment.
AB  - The 2013/2014 Community Structure-Activity Resource (CSAR) challenge was designed
      to prospectively validate advancement in the field of docking and scoring
      receptor-small molecule interactions. Purely computational methods have been
      found to be quite limiting. Thus, the challenges assessed methods that combined
      both experimental data and computational approaches. Here, we describe our
      contribution to solve three important challenges in rational drug discovery: rank
      ordering protein primary sequences based on affinity to a compound, determining
      close-to-native bound conformations out of a set of decoy poses, and rank
      ordering sets of congeneric compounds based on affinity to a given protein. We
      showed that the most significant contribution to a meaningful enrichment of
      native-like models was the identification of the best receptor structure for
      docking and scoring. Depending on the target, the optimal receptor for cross
      docking and scoring was identified by a self-consistent docking approach that
      used the Vina scoring function, by aligning compounds to the closest cocrystal or
      by selecting the cocrystal receptor with the largest pocket. For tRNA (m1G37)
      methyltransferase (TRMD), ranking a set of 31 congeneric binding compounds cross
      docked to the optimal receptor resulted in a R(2) = 0.67; whereas, using any
      other of the 13 receptor structures led to almost no enrichment of native-like
      complex structures. Furthermore, although redocking predicted lower RMSDs
      relative to the bound structures, the ranking based on multiple receptor
      structures did not improve the correlation coefficient. Our predictions highlight
      the role of rational structure-based modeling in maximizing the outcome of
      virtual screening, as well as limitations scoring multiple receptors.

PMID- 26222932
TI  - Variable density randomized stack of spirals (VDR-SoS) for compressive sensing
      MRI.
AB  - PURPOSE: To develop a 3D sampling strategy based on a stack of variable density
      spirals for compressive sensing MRI. METHODS: A random sampling pattern was
      obtained by rotating each spiral by a random angle and by delaying for few time
      steps the gradient waveforms of the different interleaves. A three-dimensional
      (3D) variable sampling density was obtained by designing different variable
      density spirals for each slice encoding. The proposed approach was tested with
      phantom simulations up to a five-fold undersampling factor. Fully sampled 3D
      dataset of a human knee, and of a human brain, were obtained from a healthy
      volunteer. The proposed approach was tested with off-line reconstructions of the
      knee dataset up to a four-fold acceleration and compared with other noncoherent
      trajectories. RESULTS: The proposed approach outperformed the standard stack of
      spirals for various undersampling factors. The level of coherence and the
      reconstruction quality of the proposed approach were similar to those of other
      trajectories that, however, require 3D gridding for the reconstruction.
      CONCLUSION: The variable density randomized stack of spirals (VDR-SoS) is an
      easily implementable trajectory that could represent a valid sampling strategy
      for 3D compressive sensing MRI. It guarantees low levels of coherence without
      requiring 3D gridding. Magn Reson Med 76:59-69, 2016. (c) 2015 Wiley Periodicals,
      Inc.

PMID- 26222933
TI  - Can low urinary tract symptoms influence postprostatectomy urinary incontinence?
AB  - BACKGROUND: The aim of this study was to analyze what kind of urinary symptoms
      patients have before receiving treatment by radical prostatectomy (RP), and to
      evaluate their influence on urinary incontinence (UI). METHODS: Between 2002 and
      2012, 758 consecutive patients underwent RP for clinically localized prostate
      cancer (PCa). Surgery was carried out by open retropubic RP in 545 (73.1%) of
      patients and laparoscopic RP in 201 (27%) by 5 surgeons who were excluded from
      data collection and analysis. The following symptoms were collected from the last
      urological check-ups or pre-operative consultation and classified as: storage
      symptoms, voiding symptoms, post micturition symptoms, history of acute urinary
      retention, benign prostatic hyperplasia treatment, history of transurethral
      resection of the prostate (TURP). RESULTS: A total of 661 patients were included
      on analysis: 136 (20.6%) patients reported low urinary tract symptoms (LUTS), 162
      (24.5%) were considered incontinent after RP, and 45 (33.1%) of them reported
      LUTS before surgery. Postprostatectomy urinary incontinence (PPUI) was
      significantly different in patients with LUTS (117 [22.3%] vs. 45 [33.1%],
      P=0.009). The presence of any LUTS influence significantly in the appearance of
      PPUI (OR=1.72 [95% CI: 1.14-2.6), P=0.01). TURP is independently influential in
      PPUI (OR=6.13 [95% CI: 1.86-20.18], P=0.003). A patient with LUTS before surgery
      has an increased risk of 70% or even 200% to suffer PPUI and a patient who
      received treatment by TURP is 6 times at higher risk of PPUI. CONCLUSIONS: In
      conclusion, patients with LUTS are likely to present PPUI. History of TURP is
      influential by itself over PPUI. A good preoperative consultation is important to
      assess continence status and to create realistic expectations to patients before
      RP.

PMID- 26222934
TI  - Psychological well-being of patients with insomnia and its relationship with
      anxiety and depression.
AB  - The aims of the present study are to evaluate the impact of insomnia on
      psychological well-being and to examine the associations of insomnia and
      psychological well-being with anxiety and depression. Forty-one patients
      attending our hospital-based Centre for sleep medicine were administered scales
      for the evaluation of insomnia (ISI), anxiety (STAI-Y), depression (BDI-II) and
      psychological well-being (PWB). The scores were compared to those of a control
      group of 68 subjects attending the hospital for routine examinations or as
      accompanying persons. Significant differences between patients and controls were
      detected for anxiety and depression, as well as for psychological well-being.
      Even if subclinical on average, anxiety and depression symptoms were
      significantly related to poor psychological well-being, whereas insomnia per se
      was not. These findings suggest that patients with insomnia report a relevant
      impact on their psychological well-being, and that such an impact seems to be
      strongly associated with concomitant subthreshold symptoms of anxiety and
      depression. The implications for diagnosis and treatment are discussed. 

PMID- 26222936
TI  - The impact of noise exposure on workers in Mobile Support Units.
AB  - PURPOSE: To investigate the presence of auditory and nonauditory symptoms in
      professionals working in ambulances. METHODS: This was a descriptive cross
      sectional study with a convenience sample. Thirty-six professionals working in
      mobile support units, including drivers and nursing technicians from two private
      urgency and emergency services in the city of Belo Horizonte, Minas Gerais,
      Brazil, participated in the study. A questionnaire containing 17 multiple-choice
      questions was applied to the participants with questions regarding life history
      and occupation, family history of hearing loss, use of medications, and presence
      of auditory and nonauditory symptoms, among others. The professionals answered
      the questionnaire individually, in their workplaces, and received help from the
      researcher to understand the content of questions, if needed. Data were
      statistically analyzed using the Statistical Package for the Social Sciences
      (SPSS) software, version 16.0. RESULTS: The most reported auditory symptoms were
      tinnitus, intolerance to intense sounds, and ear plenitude. The most reported
      nonauditory symptoms were irritability, headache, talking difficulties in noisy
      environments, and sleep alterations. A difference (p<=0.05) was observed when the
      relation between self-perception of drivers and nursing technicians on hearing
      acuity, presence of tinnitus, irritability, and communication difficulty was
      analyzed. CONCLUSION: Auditory and nonauditory symptoms are frequent in workers
      from mobile support units. An association between the worker's symptoms and the
      performed function was also observed. The results indicate a need of developing
      preventive actions regarding general health, which are aimed at the preservation
      of hearing health and quality of life of these professionals.

PMID- 26222937
TI  - Acoustic reflex on newborns: the influence of the 226 and 1,000 Hz probes.
AB  - PURPOSE: To analyze the occurrence of acoustic reflex and its threshold on
      newborns using the 226 and 1,000 Hz probes. METHODS: Thirty-six newborns with
      "PASS" results in newborn hearing screening and tympanogram with one or two peaks
      for both probe tones were included. Group I comprised 20 full-term newborns
      without risk indicator for hearing loss, and Group II comprised 16 newborns with
      at least one risk indicator. The study about ipsilateral acoustic reflex
      thresholds was conducted in 500, 1,000, 2,000, and 4,000 Hz. RESULTS: The groups
      presented the acoustic reflex thresholds between 50 and 100 dB for both probe
      tones. In the comparison between the probes, there were differences in all
      frequencies evaluated in Group I, with the lowest threshold mean for the 1,000 Hz
      probe. In Group II, differences were detected at 2,000 Hz. The mean acoustic
      reflex thresholds were similar in both groups for the 226 Hz probe. There was a
      difference for the 1,000 Hz probe in all tested frequencies. The percentage of
      response was higher in both groups for the 1,000 Hz probe. The kappa test showed
      extremely poor agreement in the comparison of results between both probes.
      CONCLUSION: The occurrence of acoustic reflex was higher in newborns and its
      thresholds were lower with the 1,000 Hz probe both for healthy newborns and for
      newborns at risk.

PMID- 26222938
TI  - Characteristics of the acquisition of sonorant consonants orthography in
      Brazilian children from a Sao Paulo municipality.
AB  - PURPOSE: To describe the spelling performance of children with regard to the
      record of sonorant consonants in Brazilian Portuguese language, to verify if the
      errors in their records were influenced by the accent in the word, and to
      categorize the kinds of errors found. METHODS: For this current survey, 801 text
      productions were selected as a result of the development of 14 different thematic
      proposals, prepared by 76 children from the first grade of primary school, in
      2001, coming from two schools of a city from Sao Paulo, Brazil. Of these
      productions, all words with sonorant consonants in a syllabic position of simple
      onset were selected. They were then organized as they appeared as pre-tonic,
      tonic, and post-tonic syllables, unstressed and tonic monosyllables. RESULTS: The
      following was observed: the number of hits was extremely higher than that of
      errors; higher occurrence of errors in non-accented syllables; higher occurrence
      of phonological substitutions followed by omissions and, at last, orthographic
      substitutions; and higher number of substitutions that involved graphemes
      referring to the sonorant class. CONCLUSION: Considering the distribution of
      orthographic data between hits and errors, as well as their relationship with
      phonetic-phonological aspects, may contribute to the comprehension of school
      difficulties, which are usually found in the first years of literacy instruction.

PMID- 26222939
TI  - Phonemic discrimination and the relationship with other linguistic levels in
      children with typical phonological development and phonological disorder.
AB  - PURPOSE: To compare children with typical language development (TLD) and
      evolutional phonological disorder (EPD) regarding the phonemic discrimination and
      the linguistic performance of language levels (morphological, syntactic,
      semantic, and perceptual and productive vocabulary). METHODS: The sample
      comprised 36 children, aged between 5 years and 7 years and 11 months, with TLD
      and EPD. Children with EPD were awaiting care in the speech units of two higher
      education institutions and children with TLD were screened in public schools. For
      inclusion in the study, the criteria were the following: being authorized by the
      informed consent and being within the required age group. After the inclusion of
      children, all subjects underwent the phonemic discrimination test with figures,
      to the average phrase value test, which assesses the morphosyntactic and
      semantic/lexical aspects, and the expressive vocabulary test. For statistical
      evaluation of the influence of variables, Spearman's nonparametric correlation
      coefficient was used, and for comparison between the groups regarding evaluation
      performance, Mann-Whitney test was used. RESULTS: Only children with EPD showed
      influence of phonemic discrimination in other linguistic levels. In addition, a
      significant difference was observed between the performances of both groups in
      relation to the phonemic discrimination, vocabulary, and all levels assessed in
      the questions and description modality. CONCLUSION: The comparison between both
      groups showed a statistically significant difference in phonemic discrimination
      and morphosyntactic and lexical/semantic development, with better performance in
      the TLD group.

PMID- 26222940
TI  - Profile of reading accuracy acquisition of students from elementary school.
AB  - PURPOSE: To characterize the profile of reading accuracy acquisition of children
      from the elementary school, considering word extension and syllabic structure.
      METHODS: This study counted on 29 children from the third grade and 28 from the
      fourth grade of the Brazilian elementary school, with mean age of 8:5 and 9:3
      years, respectively, who did not present learning disorders. All participants
      underwent oral reading assessment through texts according to each school level.
      The texts were analyzed considering the range of word length and syllabic
      structure. The performance of the students was analyzed according to the accuracy
      percentage concerning word length and syllabic structure. All data underwent
      statistical analysis. RESULTS: We noticed that the variability in the percentage
      increased due to the number of syllables, with more incidences of error in
      students from the third year. Furthermore, data pointed out greater accuracy of
      students from the fourth year with regard to word length and syllabic structure.
      Analysis of variance with repeated measures indicated interaction effect between
      both groups and the studied variables. CONCLUSION: This study showed evidence
      that word length is a strong factor to reading accuracy acquisition in Brazilian
      Portuguese. In addition, words with syllabic structure different from the pattern
      commonly seen in the Portuguese language are more difficult to be read by
      children of lower schooling levels.

PMID- 26222941
TI  - Dysarthria and Quality of Life in neurologically healthy elderly and patients
      with Parkinson's disease.
AB  - PURPOSE: To compare the speech and voice of Parkinson's disease (PD) patients and
      neurologically healthy elderly adults (control group, CG), to find out whether
      these features are related to the disease or the normal aging process, and
      investigate the impact that dysarthria has on the Quality of Life (QoL) of these
      individuals. METHODS: This is a cross-sectional study involving 25 individuals,
      13 patients with PD and 12 CG. All the participants underwent vocal assessment,
      perceptual and acoustic analysis, based on "Dysarthria Assessment Protocol" and
      analysis of QoL using a questionnaire, "Living with Dysarthria". The data
      underwent statistical analysis to compare the groups in each parameter. RESULTS:
      In the assessment of dysarthria, patients with PD showed differences in prosody
      parameter (p=0.012), at the habitual frequency for females (p=0.025) and males
      (p=0.028), and the extent of intensity (p=0.039) when compared to CG. In QoL
      questionnaire, it was observed that patients with PD showed more negative impact
      on the QoL compared to CG, as indicated by the total score (p=0.005) with various
      aspects influencing this result. CONCLUSION: The degree of modification of speech
      and voice of patients with PD resembles those seen in normal aging process, with
      the exception of prosody and the habitual frequency, which are related to the
      greatest negative impact on the QoL of patients with PD.

PMID- 26222942
TI  - Orofacial functions and quality of life in oral health in subjects with
      dentofacial deformity.
AB  - PURPOSE: To investigate the influence of the facial pattern in orofacial
      functions (OFFs) and quality of life (QoL), and their relationship in individuals
      with dentofacial deformities (DFD). METHODS: As approved by the Research Ethics
      Committee, 36 subjects, aged between 18 and 40 years, divided into three groups
      of seven female and five male participants, i.e., facial pattern I (n=12),
      pattern II (n=12) and pattern III (n=12), participated in this study. The OFFs
      were assessed using the MBGR protocol and QoL by the Oral Health Impact Profile
      (OHIP-14) questionnaire. Comparisons between OFFs and facial patterns were made
      using the Kruskal-Wallis test, and the correlation between the facial pattern and
      QoL by means of Spearman's test, considering a 5% significance level. RESULTS: A
      significant difference (p<0.05) was observed when comparing patterns I and II,
      and patterns I and III, with no difference between patterns II and III, neither
      in the OHIP-14 nor in the MBGR. A significant linear correlation (r=0.666;
      p<0.05) was verified between the MBGR and the OHIP-14, showing that the worse the
      OFFs, the worse the QoL. CONCLUSION: The facial pattern influenced the
      performance of the OFFs and the QoL in individuals presenting DFD, with a greater
      occurrence of changes for patterns II and III, and the worse the OFFs, the worse
      the QoL in cases with DFD.

PMID- 26222943
TI  - Relationship between clinical and instrumental assessment of the tongue in
      healthy young adults.
AB  - PURPOSE: To verify the association of tongue clinical evaluation aspects with
      quantitative evaluation of tongue force. METHODS: A cross-sectional study was
      conducted with 48 healthy adults, 13 men and 35 women (ages 20-44 years; mean -
      M=24.8 years; standard deviation - SD=5.3 years). By clinical evaluation, the
      following aspects were checked: tongue force, alternate movements, snap, suction
      and vibration of the tongue. The evaluator also checked if the floor of the mouth
      elevated during tasks of tongue elevation and sucking tongue on palate and the
      occurrence of lingual tremor. Quantitative evaluation was accomplished using the
      FORLING instrument. It is composed of a piston/cylinder assembly attached to a
      mouthguard and to a drive shaft. The force applied by the tongue to the drive
      shaft is hydraulically transmitted to a pressure sensor. Mann-Whitney's test was
      used to verify whether there were differences in average and maximum forces
      according to the characteristics assessed. The test was performed at a 5% level
      of significance. RESULTS: The aspects with the most frequent alteration were
      sucking tongue on palate and tongue vibration. Tremor had a higher occurrence
      during tongue movements. Elevation of the floor of the mouth in sucking tongue on
      palate was the only aspect associated with quantitative evaluation. CONCLUSION:
      The association between elevation of the floor of the mouth during sucking tongue
      on palate and quantitative evaluation can provide insight into the higher
      participation of the suprahyoid muscles in some participants in both tasks.

PMID- 26222944
TI  - Relationship between velopharyngeal closure, hypernasality, nasal air emission
      and nasal rustle in subjects with repaired cleft palate.
AB  - PURPOSE: To investigate the correlation among velopharyngeal closure,
      hypernasality, audible nasal air emission (NAE) and nasal rustle (NR), in
      individuals with repaired cleft palate. METHODS: One hundred patients with
      repaired cleft palate and lip, submitted to pressure-flow study for measurement
      of velopharyngeal orifice area (velopharyngeal area) and speech sample
      recordings. Velopharyngeal area was estimated during the production of the sound
      /p/ inserted in a sentence, and the velopharyngeal closure was classified as
      adequate, borderline or inadequate. Hypernasality was rated using a 4-point
      scale, NAE and NR were rated as absent or present, by three speech language
      pathologists, using recorded speech samples. Inter and intra-judge agreements
      were established. Statistical analysis was performed using the Spearman
      correlation coefficient considering p<0.05. An ordinal logistic regression model
      was developed to investigate whether the characteristics of speech can predict
      velopharyngeal closure. For this, the speech samples included in this analysis
      were those that obtained 100% agreement among raters as to the degree of
      hypernasality (43 out of 100). RESULTS: Significant correlation was found between
      hypernasality and velopharyngeal area; audible NAE and velopharyngeal area. A
      negative correlation was observed between the NR and velopharyngeal area. The
      regression analysis showed that the perceptual speech characteristics contributed
      significantly to predict the velopharyngeal closure. CONCLUSION: There is
      significant correlation between velopharyngeal closure and hypernasality, NAE and
      NR. It suggests that the perceptual speech characteristics can predict
      velopharyngeal closure, favoring the diagnosis and the definition of treatment
      conduct of velopharyngeal dysfunction.

PMID- 26222945
TI  - Organization of the referral and counter-referral system in a speech-language
      pathology and audiology clinic-school.
AB  - OBJECTIVE: To analyze the effectiveness of the referral and counter-referral flow
      in a speech-language pathology and audiology clinic-school and to characterize
      the patients' profiles. METHODS: Evaluation, retrospective, and prospective
      study, in which 503 patient records, without age restriction, were selected from
      a clinic-school and the following variables were analyzed: demographic
      information, speech and hearing diagnosis, and references. Patients were
      distributed into two groups according to the referrals made: internal (G1, n=341)
      and external (G2, n=162) to the clinic-school. RESULTS: A prevalence of male
      subjects under 12 years of age and with diagnosis of language disorders (primary
      and secondary) was found. It was observed that 83% patients in G1 were recalled
      for evaluation and speech therapy after an average of 7 months of waiting; and
      from the patients in G2 that were contacted (n=101), 13.9% were summoned and are
      satisfied with the place indicated for therapy after an average of 4 months of
      waiting. From those who did not receive care, 46% sought another service, and of
      these, 72.5% were successful. CONCLUSION: The data show the effectiveness and
      appropriateness of referrals made internally, suggesting that, when the team
      works together, the network operates more adequately. However, in relation to
      external referrals, they did not reach the proposed goals, indicating a lack of
      speech-language pathologists in public services and the low interest of patients
      in looking for other places of care.

PMID- 26222946
TI  - Auditory-perceptual evaluation of the degree of vocal deviation: correlation
      between the Visual Analogue Scale and Numerical Scale.
AB  - PURPOSE: To analyze the intra- and inter-rater agreement for visual analog scale
      and numerical scale in task of sustained vowel and to determine numerical cutoff
      points to visual analog scale corresponding to the degrees of the numeric scale.
      METHODS: We selected 205 samples of the usual task of the sustained vowel /a/.
      Six voice specialists rated the overall degree of vocal deviation, first by
      visual analog scale and, after two days, by the numeric scale. The results
      obtained by both scales were compared and the intra- and inter-rater agreement,
      the correlation between the scales, and the estimated cutoff points using the
      intraclass correlation and concordance Kappa coefficients, the Spearman
      coefficient, and analysis of variance, and the values of sensitivity and
      specificity were analyzed. RESULTS: A strong correlation was observed between the
      scales. The following numerical cutoff values were found for visual analog scale
      corresponding to the numerical scale: neutral (degree zero) - 0 to 34 mm; mild
      (degree one) - 34.1 to 51 mm; moderate (degree two) - 51.1 to 63.5 mm; intense
      (degree three) - 63.6 to 77.5 mm; and extreme (degree four) - above 77.5 mm.
      CONCLUSION: The visual analog scale and numerical scale showed a strong
      correlation, being observed the greater intra- and inter-rater agreement in
      visual analog scale. Numerical cutoff values for visual analog scale were found.
      This correlation enables the comparison between the results found in the
      evaluation of the overall degree of vocal deviation by both scales, which are
      widely used in research and in the clinical speech therapy routine.

PMID- 26222947
TI  - Self-perception, complaints and vocal quality among undergraduate students
      enrolled in a Pedagogy course.
AB  - PURPOSE: To compare the vocal self-perception and vocal complaints reported by
      two groups of students of the pedagogy course (freshmen and graduates); to relate
      the vocal self-perception to the vocal complaints for these groups; and to
      compare the voice quality of the students from these groups through perceptual
      auditory assessment and acoustic analysis. METHODS: Initially, 89 students from
      the pedagogy course answered a questionnaire about self-perceived voice quality
      and vocal complaints. In a second phase, auditory-perceptual evaluation and
      acoustic analyses of 48 participants were made through voice recordings of
      sustained vowel emission and poem reading. RESULTS: The most reported vocal
      complaints were fatigue while using the voice, sore throat, effort to speak,
      irritation or burning in the throat, hoarseness, tightness in the neck, and
      variations of voice throughout the day. There was a higher occurrence of
      complaints from graduates than from freshmen, with significant differences for
      four of the nine complaints. It was also possible to observe the relationship
      between vocal self-perception and complaints reported by these students. No
      significant differences were observed in the results of auditory-perceptual
      evaluation; however, some graduates had their voices evaluated with higher
      severity of deviation of normalcy. During acoustic analysis no difference was
      observed between groups. CONCLUSION: The increase in vocal demand by the
      graduates may have caused the greatest number and diversity of vocal complaints,
      and several of them are related to the self-assessment of voice quality. The
      auditory-perceptual evaluation and acoustic analysis showed no deviations in
      their voice.

PMID- 26222948
TI  - Frequency Modulation System and speech perception in the classroom: a systematic
      literature review.
AB  - PURPOSE: This review aimed at presenting the benefits regarding the speech
      perception in noise shown by children who wear hearing aid devices and/or
      cochlear implants with the Frequency Modulation (FM) System at school. RESEARCH
      STRATEGY: A bibliographic survey was conducted in an electronic database with
      standardized search until the year 2012, and a manual search was performed by
      using specific keywords. SELECTION CRITERIA: For the selection and evaluation of
      the scientific studies chosen in the search, criteria were established covering
      the following aspects: type of study, participants, adopted intervention, and
      evaluation of results. DATA ANALYSIS: The FM system was verified to improve
      speech perception and speech threshold in noise in all studies. RESULTS:
      Regarding the performance as to type, the best results were obtained when
      children used the personal FM system, followed by the table and the sound field
      systems. CONCLUSION: After extensive review of national and international
      literature, it was concluded that the studies indicate the need for further
      research concerning mainly the impact of the FM system on the school performance
      of children who have sensory devices coupled to the FM system. Findings in the
      literature with relation to the publications focused on speech perception in
      noise did not relate educational and auditory aspects.

PMID- 26222949
TI  - Brazilian Portuguese adaptation of Dyslexia Early Screening Test - Second
      edition: preliminary findings.
AB  - The assessment of language skills in early childhood can provide important
      information about the future of literacy and academic performances. Children with
      reading difficulties should be identified early in their education, before they
      suffer from shortcomings and experience failures and feel discouraged at school.
      Considering the importance of early identification of language disorders and the
      shortage of standardized instruments for the Brazilian scenario, the overall
      objective of this study was to translate and adapt the Dyslexia Early Screening
      Test - Second Edition (DEST-2) to, subsequently, verify its applicability and
      efficacy in preschoolers who had Brazilian Portuguese as their native language.
      The study was composed of 20 children of both genders, regularly enrolled in a
      public school in the metropolitan region of Sao Paulo, none had any complaints
      related to learning and no indicators of sensory, neurological, cognitive, or
      behavioral disorders. It was observed that there was no need for significant
      changes to the original structure of the DEST-2 or in their administration
      instructions format. The performance of the children in the translated and in the
      national exams that were used as a benchmark was compatible, suggesting that the
      adjustments made met the equivalences needed to utilize this instrument with
      Brazilian children. A randomized study that will complement the preliminarily
      data obtained is in progress. Taking into consideration the linguistic and
      cultural diversity of Brazil, it is imperative that the translated version of the
      DEST-2 can be applied on a large scale and in several states of the country, in
      order to allow the use of this instrument as a language assessment tool in
      Brazil. 

PMID- 26222950
TI  - Insight into the Mechanism of Antibacterial Activity of ZnO: Surface Defects
      Mediated Reactive Oxygen Species Even in the Dark.
AB  - A systematic and complete antibacterial study on well-designed and well
      characterized microparticle (micro), nanoparticle (nano), and capped nano ZnO has
      been carried out in both dark and light conditions with the objective of arriving
      at the mechanism of the antibacterial activity of ZnO, particularly in the dark.
      The present systematic study has conclusively proved that reactive oxygen species
      (ROS) such as (*)OH, (*)O2(-), and H2O2 are significantly produced from aqueous
      suspension of ZnO even in the dark and are mainly responsible for the activity in
      the dark up to 17%, rather than Zn(2+) ion leaching as proposed earlier. This
      work further confirms that surface defects play a major role in the production of
      ROS both in the presence and absence of light. In the dark, superoxide ((*)O2(-))
      radical mediated ROS generation through singly ionized oxygen vacancy is proposed
      for the first time, and it is confirmed by EPR and scavenger studies. ROS such as
      (*)O2(-), H2O2, and (*)OH have been estimated by UV-visible spectroscopy using
      nitro blue tetrazolium (NBT), KMnO4 titrations, and fluorescence spectroscopy,
      respectively. These are correlated to the antibacterial activity of ZnO in the
      dark and light. The activity is found to be highest for nano ZnO and least for
      micro ZnO, with capped ZnO between the two, highlighting the important role of
      surface defects in generation of ROS. The surface charge density of ZnO in dark
      and light has been estimated for the first time to the best of our knowledge, and
      it can influence antibacterial activity. Our work proposes a new mechanism
      mediated by superoxide species, for antibacterial activity of ZnO especially in
      the dark. 

PMID- 26222951
TI  - Vertical and Lateral Copper Transport through Graphene Layers.
AB  - A different mechanism was found for Cu transport through multi-transferred single
      layer graphene serving as diffusion barriers on the basis of time-dependent
      dielectric breakdown tests. Vertical and lateral transport of Cu dominates at
      different stress electric field regimes. The classic E-model was modified to
      project quantitatively the effectiveness of the graphene Cu diffusion barrier at
      low electric field based on high-field accelerated stress data. The results are
      compared to industry-standard Cu diffusion barrier material TaN. 3.5 A single
      layer graphene shows the mean time-to-fail comparable to 4 nm TaN, while two-time
      and three-time transferred single-layer graphene stacks give 2* and 3*
      improvements, respectively, compared to single-layer graphene at a 0.5 MV/cm
      electric field. The influences of graphene grain boundaries on Cu vertical
      transport through the graphene layers are explored, revealing that large-grain
      (10-15 MUm) single-layer graphene gives a 2 orders of magnitude longer lifetime
      than small-grain (2-3 MUm) graphene. As a result, it is more effective to further
      enhance graphene barrier reliability by improving single-layer graphene quality
      through increasing grain sizes or using single-crystalline graphene than just by
      increasing thickness through multi-transfer. These results may also be applied
      for graphene as barriers for other metals. 

PMID- 26222954
TI  - Profiling analysis of low molecular weight heparins by multiple heart-cutting two
      dimensional chromatography with quadruple time-of-flight mass spectrometry.
AB  - Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous
      mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is
      important for obtaining deeper insights into the structure of LMWHs. Previous
      oligosaccharide mapping methods are relatively low resolution and are unable to
      show an entire picture of the structural complexity of LMWHs. In the current
      study a profiling method was developed relying on multiple heart-cutting, two
      dimensional, ultrahigh performance liquid chromatography with quadruple time-of
      flight mass spectrometry. This represents an efficient, automated, and robust
      approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing
      reversed-phase chromatography in a two-dimensional separation, LMW components of
      different sizes and LMW components of the same size but with different charges
      and polarities can be resolved, providing a more complete picture of a LMWH.
      Structural information on each component was then obtained with quadrupole time
      of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed
      and unambiguously assigned from the LMWHs, nadroparin and enoxaparin,
      respectively. This method might be useful for quality control of LMWHs and as a
      powerful tool for heparin-related glycomics. 

PMID- 26222955
TI  - Effects of Lithium Niobate Polarization on Cell Adhesion and Morphology.
AB  - Understanding how the interfacial effects influence cell adhesion and morphology
      is of fundamental interest for controlling function, growth, and movement of
      cells in vitro and in vivo. In particular, the influence of surface charges is
      well-known but still controversial, especially when new functional materials and
      methods are introduced. Here, the influence of the spontaneous polarization of
      ferroelectric lithium niobate (LN) on the adhesion properties of fibroblast cells
      is investigated. The spontaneous polarization of LN has one of the largest known
      magnitudes at room temperature (~78 MUC/cm(2)), and its orientation can be
      patterned easily by an external voltage, this motivating highly the investigation
      of its interaction with cells. Immunofluorescence and migration assays show
      strong evidence that the surface polarity regulates the adhesion functions, with
      enhanced spreading of the cytoskeleton on the negative face. The results suggest
      the potential of LN as a platform for investigating the role of charges on
      cellular processes, thus favoring new strategies in fabricating those
      biocompatible constructs used for tissue engineering. In fact, the orientation of
      the high-magnitude polarization can be patterned easily and, in combination with
      piezoelectric, pyroelectric, and photorefractive properties, may open the route
      to more sophisticated charge templates for modulating the cell response. 

PMID- 26222956
TI  - Stress increases DNA methylation of the neuronal PAS domain 4 (Npas4) gene.
AB  - Neuronal Per Arnt Sim domain 4 (Npas4), a brain-specific helix-loop-helix
      transcription factor, was recently shown to regulate the development of GABAergic
      inhibitory neurons. Npas4 mRNA expression levels were decreased in the
      hippocampus of mice exposed to stress, which was accompanied by brain
      dysfunction. We have suggested that transient stress reduced Npas4 transcription
      through the glucocorticoid receptor. In the present report, we investigated the
      potential contribution of epigenetic modifications induced by stress on Npas4
      gene expression. The Npas4 promoter region contains two CpG islands; in the
      hippocampus, chronic restraint stress increases the DNA methylation levels of
      both of these CpG islands. In the Neuro2a cell line, treatment with a DNA
      methyltransferase inhibitor, 5-aza-2'-deoxycytidine, increased Npas4 mRNA levels
      and markedly reduced the DNA methylation levels of CpG island 2 in the Npas4
      promoter. The DNA methylation sites in CpG island 2 overlap with two cyclic
      adenosine monophosphate response element (CRE) sequences. Mutation of these CRE
      sequences reduced Npas4 promoter activity. These results suggest that
      transcription of the Npas4 gene is downregulated by stress through DNA
      methylation of its promoter. 

PMID- 26222953
TI  - Vascularisation of the central nervous system.
AB  - The developing central nervous system (CNS) is vascularised through the
      angiogenic invasion of blood vessels from a perineural vascular plexus, followed
      by continued sprouting and remodelling until a hierarchical vascular network is
      formed. Remarkably, vascularisation occurs without perturbing the intricate
      architecture of the neurogenic niches or the emerging neural networks. We discuss
      the mouse hindbrain, forebrain and retina as widely used models to study
      developmental angiogenesis in the mammalian CNS and provide an overview of key
      cellular and molecular mechanisms regulating the vascularisation of these organs.

PMID- 26222957
TI  - Do metrical incongruities disrupt semantic processing in modern Chinese? An event
      related potential study.
AB  - The present study examined the relationship between prosody and semantic
      processing in the written form of modern Chinese by analysing behavioural data
      and event-related potential data. By manipulating the number of noun syllables in
      verb-objection, we compare the dynamic neural mechanisms of the structure
      bisyllabic verb (V2)+monosyllabic noun (N1) (i.e. V2+N1) with V2+N1 (N2,
      bisyllabic noun). In Chinese, the rhythmic pattern V2+N1 is considered to be a
      metrical incongruity, whereas V2+N2 is considered to be a metrical congruity. For
      example, the verb yunshu (to transport) can be followed by liangshi (cereals).
      However, if yunshu is followed by liang (cereals), yunshu liang is usually
      considered to be metrically incongruous. This paper shows that (i) V2+N1 elicited
      more negative amplitudes than V2+N2 in the 90-170 ms and 450-500 ms windows,
      which indicates that metrical incongruities affect semantic processing in
      Chinese, and (ii) the acceptance rate for V2+N1 is significantly lower than that
      of V2+N2, which implies that metrical incongruities disrupt semantic processing
      in modern Chinese. These results are in agreement with previous studies. This is
      the first study to find that metrical incongruities disrupt semantic processing
      in Chinese. This study provides convergent evidence that metrical congruities
      facilitate semantic processing, whereas metrical incongruities disrupt semantic
      processing. Video abstract available (Supplemental digital content 1,
      http://links.lww.com/WNR/A340).

PMID- 26222958
TI  - Altered functional brain asymmetry for mental rotation: effect of estradiol
      changes across the menstrual cycle.
AB  - Mental rotation is a visuospatial task associated with pronounced sex
      differences. Performance is also affected by gonadal hormones such as
      testosterone and estradiol. To better understand hormonal modulation of the
      neural substrates of mental rotation, the present study examined the influence of
      estradiol using functional MRI. Ten premenopausal women were tested on a 3D
      mental rotation task during the early follicular and late follicular phases of
      the menstrual cycle. Change in estradiol between the two phases was confirmed by
      hormone assays. Brain activation patterns were similar across the two phases, but
      the change in estradiol had different associations with the two hemispheres.
      Better performance in the late follicular than the early follicular phase was
      associated with a pattern of reduced recruitment of the right hemisphere and
      increased recruitment of the left hemisphere. The increased recruitment of the
      left hemisphere was directly associated with greater changes in estradiol. Given
      that the right hemisphere is the dominant hemisphere in visuospatial processing,
      our results suggest that estradiol is associated with reduced functional
      asymmetry, consistent with recent accounts of hormonal modulation of
      neurocognitive function. 

PMID- 26222959
TI  - Contrast improvement of continuous wave diffuse optical tomography reconstruction
      by hybrid approach using least square and genetic algorithm.
AB  - Reconstruction of the absorption coefficient of tissue with good contrast is of
      key importance in functional diffuse optical imaging. A hybrid approach using
      model-based iterative image reconstruction and a genetic algorithm is proposed to
      enhance the contrast of the reconstructed image. The proposed method yields an
      observed contrast of 98.4%, mean square error of 0.638*10-3, and object centroid
      error of (0.001 to 0.22) mm. Experimental validation of the proposed method has
      also been provided with tissue-like phantoms which shows a significant
      improvement in image quality and thus establishes the potential of the method for
      functional diffuse optical tomography reconstruction with continuous wave setup.
      A case study of finger joint imaging is illustrated as well to show the prospect
      of the proposed method in clinical diagnosis. The method can also be applied to
      the concentration measurement of a region of interest in a turbid medium.

PMID- 26222960
TI  - Blind deconvolution estimation of fluorescence measurements through quadratic
      programming.
AB  - Time-deconvolution of the instrument response from fluorescence lifetime imaging
      microscopy (FLIM) data is usually necessary for accurate fluorescence lifetime
      estimation. In many applications, however, the instrument response is not
      available. In such cases, a blind deconvolution approach is required. An
      iterative methodology is proposed to address the blind deconvolution problem
      departing from a dataset of FLIM measurements. A linear combination of a base
      conformed by Laguerre functions models the fluorescence impulse response of the
      sample at each spatial point in our formulation. Our blind deconvolution
      estimation (BDE) algorithm is formulated as a quadratic approximation problem,
      where the decision variables are the samples of the instrument response and the
      scaling coefficients of the basis functions. In the approximation cost function,
      there is a bilinear dependence on the decision variables. Hence, due to the
      nonlinear nature of the estimation process, an alternating least-squares scheme
      iteratively solves the approximation problem. Our proposal searches for the
      samples of the instrument response with a global perspective, and the scaling
      coefficients of the basis functions locally at each spatial point. First, the
      iterative methodology relies on a least-squares solution for the instrument
      response, and quadratic programming for the scaling coefficients applied just to
      a subset of the measured fluorescence decays to initially estimate the instrument
      response to speed up the convergence. After convergence, the final stage computes
      the fluorescence impulse response at all spatial points. A comprehensive
      validation stage considers synthetic and experimental FLIM datasets of ex vivo
      atherosclerotic plaques and human breast cancer cell samples that highlight the
      advantages of the proposed BDE algorithm under different noise and initial
      conditions in the iterative scheme and parameters of the proposal.

PMID- 26222961
TI  - Development of ultraviolet- and visible-light one-shot spectral domain optical
      coherence tomography and in situ measurements of human skin.
AB  - We have developed ultraviolet (UV)- and visible-light one-shot spectral domain
      (SD) optical coherence tomography (OCT) that enables in situ imaging of human
      skin with an arbitrary wavelength in the UV-visible-light region (370-800 nm). We
      alleviated the computational burden for each color OCT image by physically
      dispersing the irradiating light with a color filter. The system consists of SD
      OCT with multicylindrical lenses; thus, mechanical scanning of the mirror or
      stage is unnecessary to obtain an OCT image. Therefore, only a few dozens of
      milliseconds are necessary to obtain single-image data. We acquired OCT images of
      one subject's skin in vivo and of a skin excision ex vivo for red (R, 650 +/- 20
      nm), green (G, 550 +/- 20 nm), blue (B, 450 +/- 20 nm), and UV (397 +/- 5 nm)
      light. In the visible-light spectrum, R light penetrated the skin and was
      reflected at a lower depth than G or B light. On the skin excision, we
      demonstrated that UV light reached the dermal layer. We anticipated that basic
      knowledge about the spectral properties of human skin in the depth direction
      could be acquired with this system.

PMID- 26222962
TI  - Spatiotemporal correlation of optical coherence tomography in-vivo images of
      rabbit airway for the diagnosis of edema.
AB  - Detection of an early stage of subglottic edema is vital for airway management
      and prevention of stenosis, a life-threatening condition in critically ill
      neonates. As an observer for the task of diagnosing edema in vivo, we
      investigated spatiotemporal correlation (STC) of full-range optical coherence
      tomography (OCT) images acquired in the rabbit airway with experimentally
      simulated edema. Operating the STC observer on OCT images generates STC
      coefficients as test statistics for the statistical decision task. Resulting from
      this, the receiver operating characteristic (ROC) curves for the diagnosis of
      airway edema with full-range OCT in-vivo images were extracted and areas under
      ROC curves were calculated. These statistically quantified results demonstrated
      the potential clinical feasibility of the STC method as a means to identify early
      airway edema.

PMID- 26222963
TI  - Photoacoustic and ultrasound imaging of cancellous bone tissue.
AB  - We used ultrasound (US) and photoacoustic (PA) imaging modalities to characterize
      cattle trabecular bones. The PA signals were generated with an 805-nm continuous
      wave laser used for optimally deep optical penetration depth. The detector for
      both modalities was a 2.25-MHz US transducer with a lateral resolution of ~1 mm
      at its focal point. Using a lateral pixel size much larger than the size of the
      trabeculae, raster scanning generated PA images related to the averaged values of
      the optical and thermoelastic properties, as well as density measurements in the
      focal volume. US backscatter yielded images related to mechanical properties and
      density in the focal volume. The depth of interest was selected by time-gating
      the signals for both modalities. The raster scanned PA and US images were
      compared with microcomputed tomography (MUCT) images averaged over the same
      volume to generate similar spatial resolution as US and PA. The comparison
      revealed correlations between PA and US modalities with the mineral volume
      fraction of the bone tissue. Various features and properties of these modalities
      such as detectable depth, resolution, and sensitivity are discussed.

PMID- 26222964
TI  - Errata: Spatially correlated microthermography maps threshold temperature in
      laser-induced damage.

PMID- 26222966
TI  - Neurobiology of Adult ADHD: Emerging Evidence for Network Dysfunctions.

PMID- 26222965
TI  - Primary Peritoneal Mesothelioma Resulting in Small Bowel Obstruction: A Case
      Report and Review of Literature.
AB  - BACKGROUND: Peritoneal mesothelioma is a rare malignancy that affects the serosal
      surfaces of the peritoneum. The peritoneum is the second most common site of
      mesothelium affected following the pleura. The aggressive nature and vague
      presentation pose many obstacles in not only diagnosis but also the treatment of
      patients with this disease. CASE REPORT: We present a case of a 76-year-old woman
      who presented with small bowel obstruction secondary to carcinomatosis secondary
      to primary peritoneal mesothelioma. The patient had multiple risk factors with
      asbestos exposure and prior therapeutic radiation. CONCLUSIONS: We discuss the
      highly varied and elusive presentation of peritoneal mesothelioma. Cumulative
      asbestos exposure, either directly or indirectly, remains the leading cause of
      mesothelioma. However, there are other non-asbestos etiologies. Small bowel
      obstruction often is a late-presenting symptom of widespread tumor burden. A
      concise review of the current diagnostic and surgical treatment of primary
      peritoneal mesothelioma demonstrates that early diagnosis and implementation
      remains vital.

PMID- 26222968
TI  - Correction.

PMID- 26222967
TI  - Pilot Study of Neurological Soft Signs and Depressive and Postconcussive Symptoms
      During Recovery From Mild Traumatic Brain Injury (mTBI).
AB  - Neurological soft signs (NSSs) tap into a variety of perceptual, motor, and
      cognitive functions. The authors administered a battery of NSSs serially to a
      group of 14 pilot patients recruited from an emergency room after they
      experienced a mild traumatic brain injury. Patients were seen within 96 hours
      after injury, and again 30 and 90 days later. Measures of balance, mood, and
      postconcussive symptoms and impairment were also obtained. NSSs and balance
      improved across visits. Across visits, NSSs and balance were not significantly
      associated with any postconcussive outcome measures, although depressive symptoms
      were. Initial neurological impairment appeared to predict subsequent residual
      postconcussive symptoms and impairment, but this result requires replication. 

PMID- 26222969
TI  - A Temporal Link Between Epileptiform Brain Activity, Schizotypy, and Pedophilia.

PMID- 26222970
TI  - Improvement of Central Sleep Apneas Following Ventricular Shunt for Normal
      Pressure Hydrocephalus.

PMID- 26222971
TI  - Transient Global Amnesia as a Presenting Manifestation of Cerebral Venous
      Thrombosis.

PMID- 26222972
TI  - Treatment of Huntington Disease and Comorbid Trichotillomania With Aripiprazole.

PMID- 26222973
TI  - Pharmacotherapy in Bipolar Depression Comorbid With Parkinson's Disease: A Case
      Report.

PMID- 26222974
TI  - Paroxetine-Related Adult-Onset Tic Disorder: A Presentation of Primary
      Progressive Multiple Sclerosis.

PMID- 26222975
TI  - Catatonia After Glioblastoma Multiforme in a Patient With Schizophrenia: The
      Importance of Establishing Etiology.

PMID- 26222976
TI  - Ictal Asomatognosia With Illusory Limb Movement Secondary to Dominant Parietal
      Lobe Lesion.

PMID- 26222977
TI  - Anti-Ma2 Antibody Encephalitis Manifesting as Cognitive Impairment and Psychosis.

PMID- 26222978
TI  - What to expect when you're expecting a hepatopancreatobiliary surgeon: self
      reported experiences of HPB surgeons from different training pathways.
AB  - BACKGROUND: Hepatopancreatobiliary (HPB) surgery fellowship training has multiple
      paths. Prospective trainees and employers must understand the differences between
      training pathways. This study examines self-reported fellowship experiences and
      current scope of practice across three pathways. METHODS: An online survey was
      disseminated to 654 surgeons. These included active Americas Hepato-Pancreato
      Biliary Association (AHPBA) members and recent graduates of HPB, transplant-HPB
      and HPB-heavy surgical oncology fellowships. RESULTS: A total of 416 (64%)
      surgeons responded. Most respondents were male (89%) and most were practising in
      an academic setting (83%). 290 (70%) respondents underwent formal fellowship
      training. Although fellowship experiences varied, current practice was largely
      similar. Minimally invasive surgery (MIS) and ultrasound were the most commonly
      identified areas of training deficiencies and were, respectively, cited as such
      by 47% and 34% of HPB-, 49% and 50% of transplant-, and 52% and 25% of surgical
      oncology-trained respondents. Non-HPB cases performed in current practice
      included gastrointestinal (GI) and general surgery cases (56% and 49%,
      respectively) for HPB-trained respondents, transplant and general surgery cases
      (87% and 21%, respectively) for transplant-trained respondents, and GI surgery
      and non-HPB surgical oncology cases (70% and 28%, respectively) for surgical
      oncology-trained respondents. CONCLUSIONS: Fellowship training in HPB surgery
      varies by training pathway. Training in MIS and ultrasound is deficient in each
      pathway. The ultimate scope of non-transplant HPB practice appears similar across
      training pathways. Thus, training pathway choice is best guided by the training
      experience desired and non-HPB components of anticipated practice.

PMID- 26222979
TI  - Weather Regulates Location, Timing, and Intensity of Dengue Virus Transmission
      between Humans and Mosquitoes.
AB  - BACKGROUND: Dengue is one of the most aggressively expanding mosquito-transmitted
      viruses. The human burden approaches 400 million infections annually. Complex
      transmission dynamics pose challenges for predicting location, timing, and
      magnitude of risk; thus, models are needed to guide prevention strategies and
      policy development locally and globally. Weather regulates transmission-potential
      via its effects on vector dynamics. An important gap in understanding risk and
      roadblock in model development is an empirical perspective clarifying how weather
      impacts transmission in diverse ecological settings. We sought to determine if
      location, timing, and potential-intensity of transmission are systematically
      defined by weather. METHODOLOGY/PRINCIPAL FINDINGS: We developed a high
      resolution empirical profile of the local weather-disease connection across Peru,
      a country with considerable ecological diversity. Applying 2-dimensional weather
      space that pairs temperature versus humidity, we mapped local transmission
      potential in weather-space by week during 1994-2012. A binary classification-tree
      was developed to test whether weather data could classify 1828 Peruvian districts
      as positive/negative for transmission and into ranks of transmission-potential
      with respect to observed disease. We show that transmission-potential is
      regulated by temperature-humidity coupling, enabling epidemics in a limited area
      of weather-space. Duration within a specific temperature range defines
      transmission-potential that is amplified exponentially in higher humidity. Dengue
      positive districts were identified by mean temperature >22 degrees C for 7+ weeks
      and minimum temperature >14 degrees C for 33+ weeks annually with 95% sensitivity
      and specificity. In elevated-risk locations, seasonal peak-incidence occurred
      when mean temperature was 26-29 degrees C, coincident with humidity at its local
      maximum; highest incidence when humidity >80%. We profile transmission-potential
      in weather-space for temperature-humidity ranging 0-38 degrees C and 5-100% at 1
      degrees C x 2% resolution. CONCLUSIONS/SIGNIFICANCE: Local duration in limited
      areas of temperature-humidity weather-space identifies potential locations,
      timing, and magnitude of transmission. The weather-space profile of transmission
      potential provides needed data that define a systematic and highly-sensitive
      weather-disease connection, demonstrating separate but coupled roles of
      temperature and humidity. New insights regarding natural regulation of human
      mosquito transmission across diverse ecological settings advance our
      understanding of risk locally and globally for dengue and other mosquito-borne
      diseases and support advances in public health policy/operations, providing an
      evidence-base for modeling, predicting risk, and surveillance-prevention
      planning.

PMID- 26222980
TI  - Efficacy of a Bio-Absorbable Antibacterial Envelope to Prevent Cardiac
      Implantable Electronic Device Infections in High-Risk Subjects.
AB  - INTRODUCTION: Cardiac implantable electronic device (CIED) infections are
      potentially preventable complications associated with high morbidity, mortality,
      and cost. A recently developed bio-absorbable antibacterial envelope (TYRXTM-A)
      might prevent CIED infections in high-risk subjects. However, data regarding
      safety and efficacy have not been published. METHODS AND RESULTS: In a single
      center retrospective cohort study, we compared the prevalence of CIED infections
      among subjects with >=2 risk factors treated with the TYRXTM-A envelope (N =
      135), the nonabsorbable TYRXTM envelope (N = 353), and controls who did not
      receive an envelope (N = 636). Infection was ascertained by individual chart
      review. The mean (95% confidence interval) number of risk factors was 3.08 (2.84
      3.32) for TYRXTM-A, 3.20 (3.07-3.34) for TYRXTM, and 3.09 (2.99-3.20) for
      controls, P = 0.3. After a minimum 300 days follow-up, the prevalence of CIED
      infection was 0 (0%) for TYRXTM-A, 1 (0.3%) for TYRXTM, and 20 (3.1%) for
      controls (P = 1 for TYRXTM-A vs. TYRXTM, P = 0.03 for TYRXTM-A vs. controls, and
      P = 0.002 for TYRXTM vs. controls). In a propensity score-matched cohort of 316
      recipients of either envelope and 316 controls, the prevalence of infection was 0
      (0%) and 9 (2.8%), respectively, P = 0.004. When limited to 122 TYRXTM-A
      recipients and 122 propensity-matched controls, the prevalence of CIED infections
      was 0 (0%) and 5 (4.1%), respectively, P = 0.024. CONCLUSIONS: Among high-risk
      subjects, the TYRXTM-A bio-absorbable envelope was associated with a very low
      prevalence of CIED related infections that was comparable to that seen with the
      nonabsorbable envelope.

PMID- 26222981
TI  - Health Care Costs and the Perioperative Surgical Home: A Survey Study.
AB  - BACKGROUND: The perceptions of anesthesiologists of US health care finance reform
      are germane to informing the future of our specialty. For this reason, we sought
      to assess anesthesiologists' views of their own importance in cost-reduction
      strategies. In addition, respondents were asked a series of questions related to
      the Perioperative Surgical Home. METHODS: A cross-sectional survey was sent
      through email to 6000 randomly chosen active members of the American Society of
      Anesthesiologists. Respondents were asked to indicate what level of
      responsibility they perceive stakeholders to have in reducing the cost of health
      care and perioperative care delivery. Respondents were then asked to describe
      their relative enthusiasm for cost-reduction strategies. To validate the primary
      outcome, we took advantage of the American Society of Anesthesiologists' recent
      focus on the Perioperative Surgical Home to ask a series of related questions as
      comparators. RESULTS: Thirty-eight percent (95% confidence interval, 35-42) of
      respondents indicated that physicians bear "major responsibility" for cost
      reduction, 58% (55-61) indicated that physicians bear "some responsibility," and
      4%, only a small fraction (0.7-7.5) indicated that physicians bear "no
      responsibility." Respondents also indicated that other entities listed bear
      "major responsibility" for cost reduction including hospitals (57% [54-61]) and
      insurance companies (54% [51-57]). Comparator data from questions not designed to
      directly measure the primary outcome are reported, including questions about the
      Perioperative Surgical Home. CONCLUSIONS: US anesthesiologists surveyed perceive
      other stakeholders, such as hospitals and insurance companies, as having a major
      responsibility in cost reduction. Furthermore, they are not enthusiastic about
      substantial financial reform such as cuts to Medicare payments.

PMID- 26222982
TI  - Screening of antioxidant activity and volatile compounds composition of Chamerion
      angustifolium (L.) Holub ecotypes grown in Lithuania.
AB  - Since biological activity of medicinal plants is dependent on cultivation area,
      climatic conditions, developmental stage, genetic modifications and other
      factors, it is important to study flora present in different growing sites and
      geographical zones. This study was focused on screening of antioxidant activity
      of C. angustifolium harvested in six different locations in Lithuania. The total
      contents of phenolic compounds, flavonoids and 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical scavenging activity were evaluated by spectrophotometric methods.
      A correlation between radical scavenging activity and total phenolic compounds
      content was observed (correlation coefficient 0.98). HPLC with online post-column
      DPPH radical scavenging reaction detection was used for the separation of
      extracts. Oenothein B, rutin and one unidentified compound were predominant.
      Volatile compounds were analysed using solid-phase microextraction coupled with
      gas chromatography-mass spectrometry. Based on the analysis of volatiles, all
      samples were classified into two chemotypes: (I) with predominant alpha- and beta
      caryophyllenes and (II) with predominant anethole. 

PMID- 26222984
TI  - Hydrothermal Synthesis g-C3N4/Nano-InVO4 Nanocomposites and Enhanced
      Photocatalytic Activity for Hydrogen Production under Visible Light Irradiation.
AB  - We synthesized g-C3N4/nano-InVO4 heterojunction-type photocatalyts by in situ
      growth of InVO4 nanoparticles onto the surface of g-C3N4 sheets via a
      hydrothermal process. The results of SEM and TEM showed that the obtained InVO4
      nanoparticles 20 nm in size dispersed uniformly on the surface of g-C3N4 sheets,
      which revealed that g-C3N4 sheets was probably a promising support for in situ
      growth of nanosize materials. The achieved intimate interface promoted the charge
      transfer and inhibited the recombination rate of photogenerated electron-hole
      pairs, which significantly improved the photocatalytic activity. A possible
      growth process of g-C3N4/nano-InVO4 nanocomposites was proposed based on
      different mass fraction of g-C3N4 content. The obtained g-C3N4/nano-InVO4
      nanocomposites could achieve effective separation of charge-hole pairs and
      stronger reducing power, which caused enhanced H2 evolution from water-splitting
      compared with bare g-C3N4 sheets and g-C3N4/micro-InVO4 composites, respectively.
      As a result, the g-C3N4/nano-InVO4 nanocomposite with a mass ratio of 80:20
      possessed the maximum photocatalytic activity for hydrogen production under
      visible-light irradiation. 

PMID- 26222983
TI  - Comparative Analysis of Cesium Chloride- and Iodixanol-Based Purification of
      Recombinant Adeno-Associated Viral Vectors for Preclinical Applications.
AB  - Cesium chloride (CsCl)- and iodixanol-based density gradients represent the core
      step in most protocols for serotype-independent adeno-associated virus (AAV)
      purification established to date. However, despite controversial reports about
      the purity and bioactivity of AAV vectors derived from each of these protocols,
      systematic comparisons of state-of-the-art variants of these methods are sparse.
      To define exact conditions for such a comparison, we first fractionated both
      gradients to analyze the distribution of intact, bioactive AAVs and contaminants,
      respectively. Moreover, we tested four different polishing methods
      (ultrafiltration, size-exclusion chromatography, hollow-fiber tangential flow
      filtration, and polyethylene glycol precipitation) implemented after the
      iodixanol gradient for their ability to deplete iodixanol and protein
      contaminations. Last, we conducted a side-by-side comparison of the CsCl and
      iodixanol/ultrafiltration protocol. Our results demonstrate that iodixanol
      purified AAV preparations show higher vector purity but harbor more (~20%) empty
      particles as compared with CsCl-purified vectors (<1%). Using mass spectrometry,
      we analyzed prominent protein impurities in the AAV vector product, thereby
      identifying known and new, possibly AAV-interacting proteins as major
      contaminants. Thus, our study not only provides a helpful guide for the many
      laboratories entering the AAV field, but also builds a basis for further
      investigation of cellular processes involved in AAV vector assembly and
      trafficking. 

PMID- 26222985
TI  - Endogenous Endophthalmitis in Patients with MRSA Septicemia: A Case Series and
      Review of Literature.
AB  - PURPOSE: To report the presentation, predisposing factors, clinical features and
      outcome in 6 eyes of 3 patients with endogenous endophthalmitis secondary to
      methicillin resistant staphylococcus aureus (MRSA) septicaemia. METHODS:
      Retrospective review of case records of 3 patients who were treated for
      endogenous endophthalmitis secondary to MRSA septicaemia in a tertiary referral
      institution. RESULTS: All three patients had systemic predisposition to
      endogenous endophthalmitis (diabetes, urosepsis). Two patients presented within 1
      week of onset of visual symptoms and the third after 3 months. Blood culture was
      positive for MRSA in all patients. Visual and anatomical improvement was noted in
      two patients who presented early. The third patient's visual outcome despite
      early treatment with intravitreal antibiotics and vitrectomy was not
      satisfactory. CONCLUSION: Endogenous endophthalmitis by MRSA is a rare but
      serious condition. Early and specific therapy based on reliable detection of the
      underlying microorganism is needed for good anatomical and functional outcome.

PMID- 26222986
TI  - Bioreducible Poly-L-Lysine-Poly[HPMA] Block Copolymers Obtained by RAFT
      Polymerization as Efficient Polyplex-Transfection Reagents.
AB  - Polylysine-b-p[HPMA] block copolymers containing a redox-responsive disulfide
      bond between both blocks are synthesized by RAFT polymerization of
      pentafluorphenyl-methacrylate with a macro-CTA from Nepsilon-benzyloxycarbonyl
      (Cbz) protected polylysine (synthesized by NCA polymerization). This polylysine-b
      p[PFMA] precursor block copolymer is converted to polylysine(Cbz)-b-p[HPMA] by
      postpolymerization modification with 2-hydroxypropylamine. After removal of the
      Cbz protecting group, cationic polylysine-b-p[HPMA] copolymers with a
      biosplittable disulfide moiety became available, which can be used as polymeric
      transfection vectors. These disulfide linked polylysine-S-S-b-p[HPMA] block
      copolymers show low cytotoxicity and increased transfection efficiencies (HEK
      293T cells) compared to analogous blockcopolymers without disulfide group making
      them interesting for the transfection of sensitive immune cells.

PMID- 26222987
TI  - A systematic review and economic evaluation of exercise referral schemes in
      primary care: a short report.
AB  - BACKGROUND: It is estimated that only 39% of men and 29% of women in England
      achieve the levels of physical activity that are recommended to protect health
      and prevent disease. One approach to addressing this problem has been the
      development of exercise referral schemes (ERSs), in which health professionals
      refer patients to external exercise providers. These schemes have been widely
      rolled out across the UK despite concerns that they may not produce sustained
      changes in levels of physical activity and, therefore, may not be cost-effective
      interventions. The evidence to determine clinical effectiveness and cost
      effectiveness was evaluated in 2009. This review seeks to update this earlier
      work by incorporating new evidence and re-examining the cost-effectiveness.
      OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of ERSs
      compared with usual care. DESIGN: Exhaustive searches of relevant electronic
      databases and journals were undertaken to identify new studies evaluating ERSs
      using a randomised controlled trial (RCT) design. RCTs that incorporated a
      qualitative evaluation of the intervention were identified in order to explore
      the barriers and facilitators to the uptake of and adherence to ERSs. Data were
      extracted using a previously designed tool and study quality assessed for
      potential bias. Where data could be pooled, meta-analyses were carried out.
      Qualitative analysis was also undertaken using a thematic approach. The cost
      effectiveness was evaluated using a Markov structure which estimated the
      likelihood of becoming physically active and the subsequent risk reduction on
      coronary heart disease (CHD), stroke and type 2 diabetes mellitus. The model
      adopts a lifetime horizon, and a NHS and Personal Social Services perspective was
      taken with discounting at 1.5% for both costs and benefits. RESULTS: The search
      identified one new RCT and one new qualitative study. The new data were pooled
      with existing data from the 2011 review by Pavey et al. [Pavey TG, Anokye N,
      Taylor AH, Trueman P, Moxham T, Fox KR, et al. The clinical effectiveness and
      cost-effectiveness of exercise referral schemes: a systematic review and economic
      evaluation. Health Technol Assess 2011;15(44)] to give a total of eight studies
      with 5190 participants. The proportion of individuals achieving 90-150 minutes of
      at least moderate-intensity activity per week at 6-12 months' follow-up was
      greater for ERSs than usual care (relative risk 1.12; 95% confidence interval
      1.04 to 1.20). Older patients and those referred for CHD risk factors appeared to
      be more likely than others to increase their levels of physical activity.
      Qualitative evidence suggests that interventions enabling the development of
      social support networks are beneficial in promoting uptake and adherence.
      Exercise referral gained 0.003 quality-adjusted life-years (QALYs) at an
      additional cost of L225 per person. The estimated mean incremental cost
      effectiveness ratio (ICER) in the probabilistic sensitivity analysis was L76,276.
      In the univariate sensitivity analysis the results were very sensitive (ICERs
      ranged from < L30,000 to > L100,000) to changes in the effect of ERSs on physical
      activity uptake and the duration of the protective effects and the direct health
      related quality-of-life gains attributable to physical activity. CONCLUSIONS:
      Exercise referral schemes result in a small improvement in the number of people
      who increase their levels of physical activity. The cost-effectiveness analysis
      indicates that the ICER for ERSs compared with usual care is around L76,000 per
      QALY, although the cost-effectiveness of ERSs is subject to considerable
      uncertainty. STUDY REGISTRATION: This study is registered as PROSPERO
      CRD42013005200. FUNDING: National Institute for Health Research Health Technology
      Assessment programme.

PMID- 26222988
TI  - Cognitive state following mild stroke: A matter of hippocampal mean diffusivity.
AB  - The hippocampus is known to play a vital role in learning and memory and was
      demonstrated as an early imaging marker for Alzheimer's disease (AD). However,
      its role as a predictor for mild cognitive impairment and dementia following
      stroke is unclear. The main purpose of this study was to examine the associations
      between hippocampal volume, mean diffusivity (MD) and connectivity and cognitive
      state following stroke. Eighty three consecutive first ever mild to moderate
      stroke or transient ischemic attack (TIA) survivors from our ongoing prospective
      TABASCO (Tel Aviv Brain Acute Stroke Cohort) study underwent magnetic resonance
      imaging scans within 7 days of stroke onset. Hippocampal volume was measured from
      T1 weighted images, hippocampal mean diffusivity was calculated from diffusion
      tensor imaging and connectivity was calculated from resting state fMRI. Global
      cognitive assessments were evaluated during hospitalization and 6 and 12 months
      later using a computerized neuropsychological battery. Multiple linear regression
      analysis was used to test which of the hippocampi measurements best predict
      cognitive state. All three imaging parameters were significantly correlated to
      each other (|r's| >0.3, P's < 0.005), and with cognitive state 6 and 12 months
      after the event. Multiple regression analyses demonstrated the predictive role of
      hippocampal mean diffusivity (beta = -0.382, P = 0.026) on cognitive state, above
      and beyond that of volume and connectivity of this structure. To our knowledge,
      the combination of hippocampal volume, mean diffusivity and connectivity in first
      ever post stroke or TIA patients has not yet been considered in relation to
      cognitive state. The results demonstrate the predictive role of hippocampal mean
      diffusivity, suggesting that these changes may precede and contribute to
      volumetric and connectivity changes in the hippocampi, potentially serving as a
      marker for early identification of patients at risk of developing cognitive
      impairment or dementia.

PMID- 26222989
TI  - Biological Therapies for Atrial Fibrillation: Ready for Prime Time?
AB  - Atrial fibrillation is a prominent cause of morbidity and mortality in developed
      countries. Treatment strategies center on controlling atrial rhythm or
      ventricular rate. The need for anticoagulation is an independent decision from
      the rate versus rhythm control debate. This review discusses novel biological
      strategies that have potential utility in the management of atrial fibrillation.
      Rate controlling strategies predominately rely on G-protein gene transfer to
      enhance cholinergic or suppress adrenergic signaling pathways in the
      atrioventricular node. Calcium channel blocking gene therapy and fibrosis
      enhancing cell therapy have also been reported. Rhythm controlling strategies
      focus on disrupting reentry by enhancing conduction or suppressing
      repolarization. Efforts to suppress inflammation and apoptosis are also under
      study. Resistance to blood clot formation has been shown with thrombomodulin.
      These strategies are in various stages of preclinical development. 

PMID- 26222990
TI  - The Impact of Novel Anticoagulants: Should All AF Patients Now Be Anticoagulated?
AB  - Atrial Fibrillation (AF) is accompanied by an increased risk for thromboembolic
      events in most affected patients. Current guidelines therefore recommend
      antithrombotic therapy with vitamin K antagonist (VKA) or non VKA oral
      anticoagulant (NOAC) in the majority of AF patients. Current AF treatment
      guidelines recommend that only patients younger than 65 years of age with lone
      AF, meaning without further concomitant risk factors for thromboembolic events
      should not be anticoagulated. NOACs, like the direct thrombin inhibitor
      dabigatran and the factor X inhibitors rivaroxaban, apixaban, and edoxaban have
      undergone large phase III clinical trials concerning treatment efficacy and
      bleeding risk in comparison to the VKA warfarin. In most cases, treatment with
      NOACs has been shown to decrease thromboembolic risk and/or decrease bleeding
      risk when compared with warfarin. Especially, as major hemorrhages like life
      threatening or intracranial bleeds are reduced, the question arises, if due to
      favourable adverse event ratios the indication for oral anticoagulation therapy
      should be broadened and all patients with diagnosed AF should be anticoagulated.
      This article gives a review on currently used thromboembolic and bleeding risk
      scores. Furthermore, the impact of NOAC therapy on stroke and bleeding risk is
      summarized, especially taking pharmacological interactions of NOAC therapy
      altering thromboembolic or bleeding risk into consideration. Differences of
      currently available guidelines are discussed. Finally, ongoing recent studies on
      treatment of low risk patients are debated. 

PMID- 26222991
TI  - Selective Heart Rate Reduction Improves Metabolic Syndrome-related Left
      Ventricular Diastolic Dysfunction.
AB  - BACKGROUND: Enhanced heart rate observed in metabolic syndrome (MS) contributes
      to the deterioration of left ventricular (LV) function via impaired LV filling
      and relaxation, increased myocardial O2 consumption, and reduced coronary
      perfusion. However, whether heart rate reduction (HRR) opposes LV dysfunction
      observed in MS is unknown. METHODS: We assessed in Zucker fa/fa rats, a rat model
      of MS, the cardiovascular effects of HRR induced by the If current inhibitor
      S38844 (3 mg . kg(-1) . d(-1)). RESULTS: Delayed short-term (4 days) and long
      term (90 days) HRR induced by S38844 reduced LV end-diastolic pressure and LV end
      diastolic pressure-volume relation, increased myocardial tissue perfusion,
      decreased myocardial oxidized glutathione levels, and preserved cardiac output,
      without modifying LV end-systolic pressure and LV end-systolic pressure-volume
      relation, although only long-term S38844 opposed LV collagen accumulation. Long
      term S38844 improved flow-induced endothelium-dependent dilatation of mesenteric
      arteries, while metabolic parameters, such as plasma glucose levels, and Hb1c,
      were never modified. CONCLUSIONS: In rats with MS, HRR induced by the If
      inhibitor S38844 improved LV diastolic function and endothelium-dependent
      vascular dilatation, independent from modifications in metabolic status.
      Moreover, this improvement in cardiac function involves not only immediate
      effects such as improved myocardial perfusion and reduced oxidative stress but
      also long-term effects such as modifications in the myocardial structure.

PMID- 26222992
TI  - Combining Epinephrine and Esmolol Attenuates Excessive Autophagy and Mitophagy in
      Rat Cardiomyocytes After Cardiac Arrest.
AB  - BACKGROUND: Recent experimental and clinical studies have indicated that the beta
      adrenergic effect of epinephrine significantly increases the severity of
      postresuscitation myocardial dysfunction. The aim of this study was to
      investigate whether the short-acting beta1-selective adrenergic blocking agent,
      esmolol, would impact postresuscitation autophagy and mitophagy in cardiomyocytes
      in a rat cardiac arrest (CA) model. METHODS: CA was induced in Sprague Dawley
      rats by epicardial ventricular fibrillation for 5 minutes. After successful
      resuscitation, the surviving rats were randomly divided into 2 groups that
      received femoral venous injections of epinephrine combined with either esmolol
      (EE group) or epinephrine (E group). Arterial blood samples were obtained at
      times 0, 30, and 180 minutes after return of spontaneous circulation. Surviving
      rats were euthanatized at 12 or 24 hours after return of spontaneous circulation,
      and the hearts were removed for histochemical analysis, electron microscopy,
      Western blotting, and TUNEL experiment. RESULTS: Relative to the E group, the EE
      group had reduced N-Methyl-D-Aspartate receptors expression and reduced arterial
      lactate levels (P < 0.05), suggesting that epinephrine/esmolol can attenuate
      postresuscitation antioxidation and apoptosis. This protective effect also
      correlated with a reduction of excessive autophagy and mitophagy in the
      cardiomyocytes, as evidenced by a reduction in Beclin-1 and Parkin expression (P
      < 0.05). CONCLUSIONS: Esmolol significantly alleviates postresuscitational
      autophagy, including mitophagy, and cardiomyocyte apoptosis in a rat CA model.

PMID- 26222993
TI  - Association Between Bisphosphonates Therapy and Incident Myocardial Infarction:
      Meta-analysis and Trial Sequential Analysis.
AB  - BACKGROUND: Bisphosphonates have shown potential to inhibit atherosclerosis in
      animal experiments; however, whether bisphosphonates therapy lowers the risk of
      incidence of myocardial infarction (MI) is debated. We performed the meta
      analysis and trial sequential analysis (TSA) to investigate the relation between
      bisphosphonates therapy and incident MI. METHODS: Pubmed and Embase databases
      were systematically searched in April 2015 to identify studies, which compared
      the incidence of MI in subjects receiving bisphosphonates with that in subjects
      not receiving the agents. Meta-analysis was conducted using random effects model
      in consideration of statistical heterogeneity between studies. Reliability of the
      results from meta-analysis was examined using TSA. RESULTS: Six observational
      studies (n = 440261) and 3 randomized control trials (RCTs, n = 11,024) met the
      eligible criteria. In the pooled analysis of observational studies,
      bisphosphonates therapy was not associated with reduced risk of MI either using
      unadjusted estimates (relative risk 0.93, 95% confidence interval (CI), 0.75
      1.15) or estimates adjusted for confounding factors (hazard ratio 1.01, 95% CI,
      0.84-1.21). Furthermore, hazard of incident MI did not differ between alendronate
      users and nonusers. TSA showed that evidence from observational studies firmly
      precluded the association between bisphosphonates and incident MI. Pooled
      analysis of RCTs also suggested no benefits of decrease in incident MI associated
      with bisphosphonates therapy (relative risk 1.05, 95% CI, 0.53-2.09). However,
      TSA demonstrated that evidence from RCTs was insufficient to draw a conclusion.
      CONCLUSIONS: Despite the encouraging findings from animal studies,
      bisphosphonates therapy is not associated with reduced risk of MI.

PMID- 26222994
TI  - Evaluation of an optimal preparation of human standardized fecal inocula for in
      vitro fermentation studies.
AB  - This study investigated the optimal preservation approach to prepare human feces
      as inoculum for in vitro fermentations as an alternative to the use of fresh
      feces. The four treatments studied were: Treatment 1) fresh feces resuspended in
      dialysate solution+glycerol; Treatment 2) fresh feces resuspended in dialysate
      solution+glycerol and then stored at -80 degrees C; Treatment 3) fecal sample
      frozen with 1.5 g glycerol; and Treatment 4) fecal sample frozen. All the
      treatments contained 8.75 g of feces, 3.5 ml dialysate and 4.9 ml glycerol when
      inoculated in TIM-2 in vitro system. Treatment 1 (fresh fecal preparation) was
      used as a reference. The effects were evaluated in terms of i) metabolic activity
      and ii) composition of the microbiota using fermentation experiments in the TIM-2
      in vitro system. In all treatments, high levels of acetate were produced followed
      by n-butyrate and propionate. However, the metabolic activity of the bacteria, in
      terms of short-chain fatty acid production, was affected by the different
      treatments. Microbiota composition was analyzed using the IS-pro profiling
      technique. Diversity in Actinobacteria, Firmicutes, Fusobacteria and
      Verrucomicrobia and Proteobacteria groups seemed to be preserved in all
      treatments whereas it was observed to decline in the Bacteroidetes group.
      Preparing a human fecal inoculum resuspended in dialysate solution with glycerol
      and then stored at -80 degrees C showed high similarities to the results obtained
      with fresh feces, and is proposed as the optimal way to freeze fecal material as
      an alternative to fresh feces for in vitro fermentation studies.

PMID- 26222995
TI  - Characterization of amniotic fluid of Dohne Merino ewes (Ovis aries) and its
      possible role in neonatal recognition.
AB  - Amniotic fluid (AF) was investigated as a possible source of the neonatal
      recognition cue that plays a crucial role in ewe-lamb bonding in sheep. A total
      of 70 of the 133 volatile organic compounds (VOCs), previously identified in the
      cranial wool of neonatal Dohne Merino lambs, was also identified in AF collected
      individually from neonatal twins. As in the case of the wool of neonatal lambs,
      the VOC profiles (GC-MS) of the AF of twins were remarkably similar. However, the
      VOC profiles of the AF differed from that of the wool VOCs of the same lambs. The
      VOCs that best represent the total variance in the AF and wool of neonatal lambs
      were not identified as ligands of the AF proteins. These observations suggest
      that it is unlikely that the neonatal recognition cue of sheep could be a
      maternal label derived from the AF in which a lamb is born, and that the neonatal
      recognition cue is probably produced by the lamb. Taking cognizance of the
      temporal changes that take place in the quantitative composition of the cranial
      wool VOCs, we hypothesize that components of the neonatal recognition cue are
      already produced by the lamb well before its birth and that the quantitative
      composition in which these volatiles are released into the AF does not correspond
      to the composition of the recognition cue of the lamb at its birth. When grooming
      the newborn lamb, its mother removes AF containing incorrect chemical information
      from her lamb's body and this affords her enough time to learn its personal
      recognition cue. 

PMID- 26222996
TI  - Evaporation of decamethylcyclopentasiloxane (D5) from selected cosmetic products:
      Implications for consumer exposure modeling.
AB  - Consumer exposure to leave-on cosmetics and personal care products (C&PCPs)
      ingredients of low or moderate volatility is often assumed to occur primarily via
      dermal absorption. In reality they may volatilize from skin and represent a
      significant source for inhalation exposure. Often, evaporation rates of pure
      substances from inert surfaces are used as a surrogate for evaporation from more
      complex product matrices. Also the influence of partitioning to skin is neglected
      and the resulting inaccuracies are not known. In this paper we describe a novel
      approach for measuring chemical evaporation rates from C&PCPs under realistic
      consumer exposure conditions. Series of experiments were carried out in a custom
      made ventilated chamber fitted with a vapor trap to study the disposition of a
      volatile cosmetic ingredient, decamethylcyclopentasiloxane (D5), after its
      topical application on either aluminum foil or porcine skin in vitro. Single
      doses were applied neat and in commercial deodorant and face cream formulations
      at normal room (23 degrees C) and skin temperature (32 degrees C). The condition
      specific evaporation rates were determined as the chemical mass loss per unit
      surface area at different time intervals over 1-1.25h post-dose. Product weight
      loss was monitored gravimetrically and the residual D5 concentrations were
      analyzed with GC/FID. The release of D5 from exposed surfaces of aluminum
      occurred very fast with mean rates of 0.029 mg cm(-2)min(-1) and 0.060 mg cm(
      2)min(-1) at 23 degrees C and 32 degrees C, respectively. Statistical analysis of
      experimental data confirmed a significant effect of cosmetic formulations on the
      evaporation of D5 with the largest effect (2-fold decrease of the evaporation
      rate) observed for the neat face cream pair at 32 degrees C. The developed
      approach explicitly considers the initial penetration and evaporation of a
      substance from the Stratum Corneum and has the potential for application in
      dermal exposure modeling, product emission tests and the formulation of C&PCPs.

PMID- 26222997
TI  - Evaluation of Renal Arteries of 286 Living Donors by Multidetector Computed
      Tomography Angiography: A Single-Center Study.
AB  - OBJECTIVES: In living renal donors, digital subtraction angiography and
      intravenous pyelogram techniques developing traditional evaluation before
      transplant have started to give place to more modern and less-invasive methods
      such as multidetector computerized tomography angiography, and magnetic resonance
      angiography via the developments in the imaging technology. We aimed to evaluate
      the renal arteries of living-renal donors by multidetector computerized
      tomography angiography and to compare the findings with the surgical results.
      MATERIALS AND METHODS: In our renal transplant center, 286 living-donor
      candidates to whom multi-detector computerized tomography angiography was
      applied, were evaluated retrospectively and the findings were compared with the
      surgical operation notes. RESULTS: In 180 of 286 living donor candidates to whom
      computerized tomography angiography was applied, bilateral single renal artery
      was deter-mined. In 79 renal donor candidates, unilateral multiple renal artery;
      and in 27 renal donor candidates, bilateral multiple renal artery were found. In
      58 renal donor candidates, at least 1 polar artery was specified; in 32 renal
      donor candidates, a unilateral single renal artery; in 10 renal donor candidates,
      a bilateral double renal artery was determined. When computerized tomography
      angiography and operative notes were compared, we observed that the findings in
      280 donor candidates were the same. In 6 renal donor candidates, differences in
      the findings were present. Our accuracy rate was 97% and according to the
      operative notes, our sensitivity and specificity ratios in determining multiple
      renal arteries were calculated as 98% and 95%. CONCLUSIONS: Multidetector
      computerized tomography angiography can be used rapidly and efficiently in living
      donor renal candidates with high specificity and sensitivity ratios.

PMID- 26222998
TI  - Exposure to Weight-Stigmatizing Media: Effects on Exercise Intentions,
      Motivation, and Behavior.
AB  - This study aimed to evaluate the impact of exposure to weight-stigmatizing media
      on exercise intentions, motivation, and behavior, as well as to examine the
      interaction between this exposure and past experiences with weight stigma. A
      community sample of 72 women were randomly assigned to view a brief weight
      stigmatizing or neutral video. Participants' choice of taking the stairs versus
      the elevator was observed before they completed measures of exercise intentions,
      motivation, and behavior; psychological well-being; and experiences with weight
      stigma. A follow-up survey was sent to participants 1 week later that assessed
      exercise behavior and intentions. Frequency of past weight stigma correlated with
      worse psychological well-being and more controlled (versus autonomous) exercise
      motivation. Significant interactions were found between past weight-stigmatizing
      experiences and exposure to the weight-stigmatizing video for outcomes of
      exercise intentions, behavior, and drive for thinness. Participants in the stigma
      condition with higher frequency of past experiences reported greater exercise
      intentions and behavior, along with higher drive for thinness. Past experiences
      of weight stigma interact with exposure to weight-stigmatizing media to increase
      exercise intentions and behavior, although this effect is accompanied by a
      heightened drive for thinness that may increase risk for long-term negative
      health consequences. 

PMID- 26222999
TI  - Evolutionary Visual Exploration: Evaluation of an IEC Framework for Guided Visual
      Search.
AB  - We evaluate and analyse a framework for evolutionary visual exploration (EVE)
      that guides users in exploring large search spaces. EVE uses an interactive
      evolutionary algorithm to steer the exploration of multidimensional data sets
      toward two-dimensional projections that are interesting to the analyst. Our
      method smoothly combines automatically calculated metrics and user input in order
      to propose pertinent views to the user. In this article, we revisit this
      framework and a prototype application that was developed as a demonstrator, and
      summarise our previous study with domain experts and its main findings. We then
      report on results from a new user study with a clearly predefined task, which
      examines how users leverage the system and how the system evolves to match their
      needs. While we previously showed that using EVE, domain experts were able to
      formulate interesting hypotheses and reach new insights when exploring freely,
      our new findings indicate that users, guided by the interactive evolutionary
      algorithm, are able to converge quickly to an interesting view of their data when
      a clear task is specified. We provide a detailed analysis of how users interact
      with an evolutionary algorithm and how the system responds to their exploration
      strategies and evaluation patterns. Our work aims at building a bridge between
      the domains of visual analytics and interactive evolution. The benefits are
      numerous, in particular for evaluating interactive evolutionary computation (IEC)
      techniques based on user study methodologies.

PMID- 26223000
TI  - An Effective Evolutionary Hybrid for Solving the Permutation Flowshop Scheduling
      Problem.
AB  - This paper presents an effective evolutionary hybrid for solving the permutation
      flowshop scheduling problem. Based on a memetic algorithm, the procedure uses a
      construction component that generates initial solutions through the use of a
      novel reblocking mechanism operating according to a biased random sampling
      technique. This component is aimed at forcing the operations having smaller
      processing times to appear on the critical path. The goal of the construction
      component is to fill an initial pool with high-quality solutions for a memetic
      algorithm that looks for even higher-quality solutions. In the memetic algorithm,
      whenever a crossover operator and possibly a mutation are performed, the
      offspring genome is fine-tuned by a combination of 2-exchange swap and insertion
      local searches. The same with the employed construction method; in these local
      searches, the critical path notion has been used to exploit the structure of the
      problem. The results of computational experiments on the benchmark instances
      indicate that these components have strong synergy, and their integration has
      created a robust and effective procedure that outperforms several state-of-the
      art procedures on a number of the benchmark instances. By deactivating different
      components enhancing the evolutionary module of the procedure, the effects of
      these components have also been examined.

PMID- 26223001
TI  - Diversity of endophytic and rhizoplane bacterial communities associated with
      exotic Spartina alterniflora and native mangrove using Illumina amplicon
      sequencing.
AB  - Root-associated microbial communities are very important for biogeochemical
      cycles in wetland ecosystems and help to elaborate the mechanisms of plant
      invasions. In the estuary of Jiulong River (China), Spartina alterniflora has
      widely invaded Kandelia obovata-dominated habitats, offering an opportunity to
      study the influence of root-associated bacteria. The community structures of
      endophytic and rhizosphere bacteria associated with selected plant species were
      investigated using the barcoded Illumina paired-end sequencing technique. The
      diversity indices of bacteria associated with the roots of S. alterniflora were
      higher than those of the transition stands and K. obovata monoculture. Using
      principal coordinate analysis with UniFrac metrics, the comparison of beta
      diversity showed that all samples could be significantly clustered into 3 major
      groups, according to the bacteria communities of origin. Four phyla, namely
      Proteobacteria, Bacteroidetes, Chloroflexi, and Firmicutes, were enriched in the
      rhizoplane of both salt marsh plants, while they shared higher abundances of
      Cyanobacteria and Proteobacteria among endophytic bacteria. Members of the phyla
      Spirochaetes and Chloroflexi were found among the endophytic bacteria of S.
      alterniflora and K. obovata, respectively. One of the interesting findings was
      that endophytes were more sensitive in response to plant invasion than were
      rhizosphere bacteria. With linear discriminate analysis, we found some
      predominant rhizoplane and endophytic bacteria, including Methylococcales,
      Pseudoalteromonadacea, Clostridium, Vibrio, and Desulfovibrio, which have the
      potential to affect the carbon, nitrogen, and sulfur cycles. Thus, the results
      provide clues to the isolation of functional bacteria and the effects of root
      associated microbial groups on S. alterniflora invasions. 

PMID- 26223002
TI  - Contact technique and concussions in the South African under-18 Coca-Cola Craven
      Week Rugby tournament.
AB  - In rugby union, understanding the techniques and events leading to concussions is
      important because of the nature of the injury and the severity and potential long
      term consequences, particularly in junior players. Proper contact technique is a
      prerequisite for successful participation in rugby and is a major factor
      associated with injury. However, the execution of proper contact technique and
      its relationship to injury has yet to be studied in matches. Therefore, the aim
      of this study was to compare contact techniques leading to concussion with a
      representative sample of similarly matched non-injury (NI) contact events. Injury
      surveillance was conducted at the 2011-2013 under-18 Craven Week Rugby
      tournaments. Video footage of 10 concussive events (5 tackle, 4 ruck and 1 aerial
      collision) and 83 NI events were identified (19 tackle, 61 ruck and 3 aerial
      collisions). Thereafter, each phase of play was analysed using standardised
      technical proficiency criteria. Overall score for ruck proficiency in concussive
      events was 5.67 (out of a total of 15) vs. 6.98 for NI events (n = 54) (effect
      size = 0.52, small). Overall average score for tackler proficiency was 7.25 (n =
      4) and 6.67 (n = 15) for injury and NI tackles, respectively (out of 16) (effect
      size = 0.19, trivial). This is the first study to compare concussion injury
      contact technique to a player-matched sample of NI contact techniques. Certain
      individual technical criteria had an effect towards an NI outcome, and others had
      an effect towards a concussive event, highlighting that failure to execute
      certain techniques may substantially increase the opportunity for concussion. 

PMID- 26223004
TI  - Influence of yoga and aerobics exercise on fatigue, pain and psychosocial status
      in patients with multiple sclerosis: a randomized trial.
AB  - BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease involving brain and
      spinal cord. Weakness, cognitive impairment, pain, depression and fatigue, as
      common symptoms of MS, may significantly affect on general health of MS patients.
      This study aimed to investigate the influence of yoga and aerobic exercise on
      fatigue, pain, and psychosocial status among these patients. METHODS: In a
      randomized clinical trial study on 90 patients whom were randomly assigned to
      three equal groups of yoga exercises, aerobics exercises, and control group. The
      exercise program was performed as three sessions per week for 12 weeks. The
      exercise program included 40 minutes, including 5-10 minutes for warm-up, 25-30
      minutes of exercise (walking), and 5 minutes for cooling down. Yoga exercises
      were scheduled three sessions a week for 12 weeks as well. RESULTS: There was no
      significant difference in fatigue, pain severity and psychological status among
      three groups prior to the study, but after the study, in yoga and exercise
      groups, fatigue physical function, physical and emotional role which patients
      play throughout daily life, social function, energy, mental status and overall
      hygiene increased, and the pain and fatigue were relieved in the patients.
      CONCLUSIONS: Yoga and aerobics exercise could decrease some of the MS symptoms,
      therapeutic costs, hospital stay, and days lost from work as well as increasing
      the patients' efficiency.

PMID- 26223005
TI  - Improved end-stage high-intensity performance but similar glycemic responses
      after waxy barley starch ingestion compared to dextrose in type 1 diabetes.
AB  - BACKGROUND: Pre-exercise carbohydrate (CHO) ingestion is an effective strategy
      for reducing the occurrence of hypoglycemia during or after exercise in
      individuals with type 1 diabetes (T1DM). The metabolic effects of ingestion of
      different CHOs for glycemic or performance gains have been under-researched. This
      study compared metabolic responses and fuel use during sub-maximal and high
      intensity performance running following pre-exercise ingestion of waxy barley
      starch (WBS) or dextrose (DEX) in T1DM. METHODS: Seven participants attended the
      laboratory on two separate occasions following preliminary testing. On each visit
      participants consumed either 0.6 g/kg body mass of DEX or WBS 2 hours before a 26
      minute discontinuous incremental treadmill protocol (4-minute running: 1.5-min
      rest) finishing at 80+/-4% VO2peak followed by a 10-min performance run on a non
      motorized treadmill. Capillary blood samples were taken at rest, during and
      following exercise and analyzed for glucose (BG) and acid-base variables. Data
      (mean +/- SEM) were analyzed using repeated measures ANOVA (P<0.05). RESULTS: BG
      reached similar peak values one hour after CHO ingestion and immediate pre-sub
      maximal exercise BG were comparable. Resting CHO oxidation was elevated and lipid
      oxidation lower under WBS (P<0.05). There were no metabolic or cardio-respiratory
      differences during the sub-maximal exercise (P>0.05). In the final quartile of
      the performance run, a greater distance was completed under WBS (WBS 323+/-21 vs.
      DEX 301+/-20 m, P=0.02). CONCLUSIONS: Consumption of WBS demonstrated similar
      hyperglycemic responses to dextrose ingestion but a greater rate of CHO use at
      rest. Interestingly, T1DM individuals displayed an improved performance at the
      latter stages of a high-intensity run test.

PMID- 26223006
TI  - Is the WII fit free run activity a feasible mode of exercise for regular
      exercisers: a comparison with treadmill running.
AB  - BACKGROUND: This study compared the metabolic responses between treadmill running
      and the Free Run on the Nintendo Wii when maintaining a constant pace with an aim
      to see whether this would be a feasible option for exercise in persons who
      already exercise. METHODS: Twenty eight university students, mean age 20.7+/-1.38
      years, participated in a repeated measures study. Subjects completed 10 minutes
      running on the treadmill at a self selected pace followed by 10 minutes of Free
      Run on the Nintendo Wii Fit disc. A metronome regulated the running pace during
      the Free Run activity to match the running pace on the treadmill. Oxygen
      consumption, caloric expenditure and heart rate were measured with a Cardio Coach
      Metabolic Cart. Paired t-tests compared the percentage of age predicted maximal
      oxygen consumption (% VO2max), metabolic equivalents (METs), caloric expenditure
      and percentage of estimated maximal heart rate (% HRmax) between the two running
      situations. RESULTS: For all variables of interest the mean values for treadmill
      running was found to be significantly higher than those for the Wii Free Run
      (P<0.001). The mean %HRmax and METs categorized both activities as vigorous
      intensity, however, the Free Run was at the lower end of the ranges whilst
      treadmill running was at the upper. The mean %VO2max classified treadmill running
      as vigorous intensity and Wii Free Run as moderate. CONCLUSIONS: The Wii Free Run
      activity can be used as an additional form of exercise for persons who are
      already engaged in physical activity but should not be considered a replacement
      for treadmill running by those who run.

PMID- 26223007
TI  - Assessing congenital malformation risk from medications used in pregnancy: The
      contribution of NBDPS in pregnancy labeling of prescription drug products.
AB  - BACKGROUND: Obtaining human pregnancy data to inform product labeling is
      important for drug and biological products. METHODS: Collection and analyses of
      safety data on their use during pregnancy is usually performed after approval.
      RESULTS: The Centers for Disease Control National Birth Defects Prevention Study
      has provided important data on the relationship between drug use in pregnancy and
      birth defects. CONCLUSION: The Pregnancy and Lactation Labeling Rule will set new
      and improved standards for the inclusion of information about the use of
      prescription drugs and biological products during pregnancy; the National Birth
      Defects Prevention Study, along with other data sources, will be critical for
      providing safety data to inform product labeling.

PMID- 26223009
TI  - Exploring the molecular basis of neurosteroid binding to the beta3 homopentameric
      GABAA receptor.
AB  - Neurosteroids are the principal endogenous modulators of GABA(A) receptors
      (GABA(A)Rs), which are pentameric membrane-bound proteins that regulate the
      passage of chloride ions from the extracellular to the intracellular compartment.
      As consequence of their ability to modify inhibitory functions in the brain,
      neurosteroids have high physiological and clinical importance and may act as
      anesthetic, anticonvulsant and anxiolytic drugs. Despite their relevance,
      essential issues regarding neurosteroid action on GABA(A)Rs are still unsettled.
      In particular, residues taking part of the steroid recognition are not definitely
      identified. Taking as starting point the first reported crystal structure of a
      human GABAA receptor (a beta3 homopentamer), we have explored through a
      combination of computational methods (a cavity-detection algorithm, docking and
      molecular dynamics simulations) the binding mode of two structurally different
      representative neurosteroids, pregnanolone and allopregnanolone. We have
      identified a neurosteroid binding site between the TM3 of one subunit and TM1 and
      TM4 of the adjacent subunit that is consistent with the set of experimental data
      reported for the action of neurosteroids on beta3 homopentamers. These sites are
      able to properly accommodate both overall torsioned and flat steroidal structures
      and they specifically recognize the 3-OH group, explaining the requirement of a
      3alpha-configuration for the activity. We believe that this work provides for
      first time convincing information about the molecular interaction between
      neurosteroids and a GABA(A)R. This information largely increases our
      understanding of this fundamental ligand-receptor system.

PMID- 26223010
TI  - Steroid receptor coactivator-1 mediates letrozole induced downregulation of
      postsynaptic protein PSD-95 in the hippocampus of adult female rats.
AB  - Hippocampus local estrogen which is converted from androgen that catalyzed by
      aromatase has been shown to play important roles in the regulation of learning
      and memory as well as cognition through action on synaptic plasticity, but the
      underlying mechanisms are poorly understood. Steroid receptor coactivator-1 (SRC
      1) is one of the coactivators of steroid nuclear receptors; it is widely
      distributed in brain areas that related to learning and memory, reproductive
      regulation, sensory and motor information integration. Previous studies have
      revealed high levels of SRC-1 immunoreactivities in the hippocampus; it is
      closely related to the levels of synaptic proteins such as PSD-95 under normal
      development or gonadectomy, but its exact roles in the regulation of these
      proteins remains unclear. In this study, we used aromatase inhibitor letrozole in
      vivo and SRC-1 RNA interference in vitro to investigate whether SRC-1 mediated
      endogenous estrogen regulation of hippocampal PSD-95. The results revealed that
      letrozole injection synchronously decreased hippocampal SRC-1 and PSD-95 in a
      dose-dependant manner. Furthermore, when SRC-1 specific shRNA pool was applied to
      block the expression of SRC-1 in the primary hippocampal neuron culture, both
      immunocytochemistry and Western blot revealed that levels of PSD-95 were also
      decreased significantly. Taking together, these results provided the first
      evidence that SRC-1 mediated endogenous estrogen regulation of hippocampal
      synaptic plasticity by targeting the expression of synaptic protein PSD-95.
      Additionally, since letrozole is frequently used to treat estrogen-sensitive
      breast cancer, the above results also indicate its potential side effects in
      clinical administration. 

PMID- 26223011
TI  - Load-Induced Hydrodynamic Lubrication of Porous Films.
AB  - We present an exploratory study of the tribological properties and mechanisms of
      porous polymer surfaces under applied loads in aqueous media. We show how it is
      possible to change the lubrication regime from boundary lubrication to
      hydrodynamic lubrication even at relatively low shearing velocities by the
      addition of vertical pores to a compliant polymer. It is hypothesized that the
      compressed, pressurized liquid in the pores produces a repulsive hydrodynamic
      force as it extrudes from the pores. The presence of the fluid between two
      shearing surfaces results in low coefficients of friction (MU ~ 0.31). The
      coefficient of friction is reduced further by using a boundary lubricant. The
      tribological properties are studied for a range of applied loads and shear
      velocities to demonstrate the potential applications of such materials in total
      joint replacement devices. 

PMID- 26223013
TI  - Molecular tools to understand the bioremediation effect of plants and earthworms
      on contaminated marine sediments.
AB  - A meso-scale pilot plant was set up to test the efficiency of a bioremediation
      scheme applied to marine sediments contaminated by heavy metals and hydrocarbons.
      The experiment was implemented for three years in two stages using two
      remediation agents: plants (Paspalum vaginatum and Tamarix gallica) and
      earthworms (Eisenia fetida). DNA and RNA-based methodologies were applied to
      elucidate the dynamics of the bacterial population and were related to improving
      biological and chemical conditions of the sediments. Bioremediation strategies
      were successful in removing pollutants from the contaminated sediments and
      specialization within the bacterial community related to the type of
      contamination present was detected in the different stages of the process. The
      highest response of Gram-positive PAH-degraders to the contamination was detected
      at the beginning and after the first stage of the experiment, corresponding to
      the uppermost values of degradation. 

PMID- 26223014
TI  - TiO2-sludge carbon enhanced catalytic oxidative reaction in environmental
      wastewaters applications.
AB  - The enhanced oxidative potential of sludge carbon/TiO2 nano composites (SNCs),
      applied as heterogeneous catalysts in advanced oxidation processes (AOPs), was
      studied. Fabrification of efficient SNCs using different methods and successful
      evaluation of their catalytic oxidative activity is reported for the first time.
      Surface modification processes of hydrothermal deposition, chemical treatment and
      sol-gel solution resulted in improved catalytic activity and good surface
      chemistry of the SNCs. The solids obtained after chemical treatment and
      hydrothermal deposition processes exhibit excellent crystallinity and
      photocatalytic activity. The highest photocatalytic rate was obtained for the
      material prepared using hydrothermal deposition technique, compared to other
      nanocomposites. Further, improved removal of bisphenol A (BPA) from aqueous phase
      by means of catalytic ozonation and catalytic wet air oxidation processes is
      achieved over the solid synthesized using chemical treatment method. The present
      results demonstrate that the addition of TiO2 on the surface of sludge carbon
      (SC) increases catalytic oxidative activity of SNCs. The latter produced from
      harmful sludge materials can be therefore used as cost-effective and efficient
      sludge derived catalysts for the removal of hazardous pollutants. 

PMID- 26223015
TI  - Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under
      ambient UV radiation.
AB  - Paraphenylenediamine (PPD), a derivative of paranitroaniline has been most
      commonly used as an ingredient of oxidative hair dye and permanent tattoos. We
      have studied the phototoxic potential of PPD under ambient ultraviolet radiation.
      PPD is photodegraded and form a novel photoproduct under UV A exposure. PPD shows
      a concentration dependent decrease in cell viability of human Keratinocyte cells
      (HaCaT) through MTT and NRU test. Significant intracellular ROS generation was
      measured by DCFDA assay. It caused an oxidative DNA damage via single stranded
      DNA breaks, micronuclei and CPD formation. Both lysosome and mitochondria is main
      target for PPD induced apoptosis which was proved through lysosomal
      destabilization and release of cathepsin B by immunofluorescence, real time PCR
      and western blot analysis. Cathepsin B process BID to active tBID which induces
      the release of cytochrome C from mitochondria. Mitochondrial depolarization was
      reported through transmission electron microscopy. The cathepsin inhibitor
      reduced the release of cytochrome C in PPD treated cells. Thus study suggests
      that PPD leads to apoptosis via the involvement of lysosome and mitochondria both
      under ambient UV radiation. Therefore, photosensitizing nature of hair dye
      ingredients should be tested before coming to market as a cosmetic product for
      the safety of human beings. 

PMID- 26223016
TI  - Selective adsorption of thiophenic compounds from fuel over TiO2/SiO2 under UV
      irradiation.
AB  - This study investigates selective adsorption of thiophenic compounds from fuel
      over TiO2/SiO2 under UV-irradiation. The TiO2/SiO2 adsorbents were prepared and
      then characterized by N2 adsorption, X-ray diffraction and X-ray photoelectron
      spectroscopy. Adsorption isotherms, selectivity and kinetics of TiO2/SiO2 were
      measured in a UV built-in batch reactor. It was concluded that (a) with the
      employment of UV-irradiation, high organosulfur uptake of 5.12 mg/g was achieved
      on the optimized 0.3TiO2/0.7SiO2 adsorbent at low sulfur concentration of 15 ppmw
      S, and its adsorption selectivity over naphthalene was up to 325.5; (b) highly
      dispersed TiO2 served as the photocatalytic sites for DBT oxidation, while SiO2
      acted as the selective adsorption sites for the corresponding oxidized DBT using
      TiO2 as a promoter, the two types of active sites worked cooperatively to achieve
      the high adsorption selectivity of TiO2/SiO2; (c) The kinetic rate-determining
      step for the UV photocatalysis-assisted adsorptive desulfurization (PADS) over
      TiO2/SiO2 was DBT oxidation; (d) consecutive adsorption-regeneration cycles
      suggested that the 0.3TiO2/0.7SiO2 adsorbent can be regenerated by acetonitrile
      washing followed with oxidative air treatment. This work demonstrated an
      effective PADS approach to greatly enhance adsorption capacity and selectivity of
      thiophenic compounds at low concentrations for deep desulfurization under ambient
      conditions.

PMID- 26223017
TI  - The real-time estimation of hazardous gas dispersion by the integration of gas
      detectors, neural network and gas dispersion models.
AB  - Release of hazardous materials in chemical industries is a major threat to
      surrounding areas. Current gas dispersion models like PHAST and FLACS, use
      release velocity, release elevation, meteorological parameters, and other related
      information as model input. In general, such information is not always available
      during an on-going accident. In this paper, we develop a fast prediction approach
      which could bypass the input parameters that are difficult to obtain and predict
      the released gas concentration at certain off-site location using parameters that
      could be obtained easily. The new approach is an integration of gas detectors,
      artificial neural network (ANN) and one of the aforementioned gas dispersion
      models. PHAST is applied to simulate numbers of release scenarios and the results
      containing the spatial and temporal distributions of released gas concentration
      are prepared as input and target data samples for training the neural network.
      The approach was applied to a case study involving a hypothetical chlorine
      release with varying release rates and atmospheric conditions. The results of the
      approach that are concentration and dispersion time profiles in the environmental
      sensitive locations were validated against PHAST. The validation shows highly
      correlations with PHAST and convincingly demonstrates the effectiveness of the
      proposed approach. 

PMID- 26223018
TI  - Degradation of Trichloroethene with a Novel Ball Milled Fe-C Nanocomposite.
AB  - Nanoscale zero-valent iron (NZVI) is effective in reductively degrading dense non
      aqueous phase liquids (DNAPLs), such as trichloroethene (TCE), in groundwater
      (i.e., dechlorination) although the NZVI technology itself still suffers from
      high material costs and inability to target hydrophobic contaminants in source
      zones. To address these problems, we developed a novel, inexpensive iron-carbon
      (Fe-C) nanocomposite material by simultaneously milling micron-size iron and
      activated carbon powder. Microscopic and X-ray diffraction (XRD) characterization
      of the composite material revealed that nanoparticles of Fe were dispersed in
      activated carbon and a new iron carbide phase was formed. Bench-scale studies
      showed that this material instantaneously sorbed >90% of TCE from aqueous
      solutions and subsequently decomposed TCE into non-chlorinated products. Compared
      to milled Fe, Fe-C nanocomposite dechlorinated TCE at a slightly slower rate and
      favored the production of ethene over other TCE degradation products such as C3-
      C6 compounds. When placed in hexane-water mixture, the Fe-C nanocomposite
      materials are preferentially partitioned into the organic phase, indicating the
      ability of the composite materials to target DNAPL during remediation.

PMID- 26223019
TI  - A comparative study on the heavy metal solidification/stabilization performance
      of four chemical solidifying agents in municipal solid waste incineration fly
      ash.
AB  - Investigated in this paper were the content, specification distribution, and risk
      assessment code (RAC) determination of six targeted heavy metals and potentially
      toxic metals in fly ashes from a municipal solid waste incinerator in China.
      Contained in it is a comparison of the solidification/stabilization performance
      of two novel solidifying agents of sixthio guanidine acid (SGA) and tetrathio
      bicarbamic acid (TBA) with sodium dimethyldithiocarbamate (SDD) and Na2S, and
      analysis of their leachability in accordance with TCLP 1311 of the US EPA and the
      extraction procedures of China (HJ/T 299-2007 and HJ/T300-2007). The total
      concentration of Zn, Cu, Ni, Pb, Cr, Cd is 37383.47, 3080.77, 1583.92, 1356.43,
      566.15, and 77.83 mg/kg, respectively. Cr (3.7%) and Pb (7.50%) pose low risk;
      and Ni (12.93%) and Zn (15.45%) have a medium risk; while Cu (69.84%) and Cd
      (82.5%) have a very high risk according to their RAC score. Compared with SDD and
      Na2S, SGA and TBA show an excellent overall solidifying performance due to their
      multiply hydrosulfide groups that bind with heavy metals very efficiently. The
      obtained results indicate that the leaching content of Cd, Ni, Pb and Zn is
      higher than the thresholds prescribed in GB5085.3-2007, and the excessive acetic
      acid makes its binding capacity stronger in HJ/T 300-2007 than in TCLP 1311.

PMID- 26223020
TI  - Modelling and simulation of photocatalytic oxidation mechanism of
      chlorohalogenated substituted phenols in batch systems: Langmuir-Hinshelwood
      approach.
AB  - This study investigated, modelled and simulated the influence of multi
      chlorohalogenation in heterogeneous photocatalytic degradation of substituted
      phenols (pentachlorophenol (PCP), trichlorophenol (TCP), dichlorophenol (DCP),
      and monochlorophenol (CP)). The Langmuir-Hinshelwood approach was applied to
      determine oxidation kinetics. Aquasim 2.0 computational software was used to
      model, simulate and estimate model parameters of the different chlorophenols.
      Chemical adsorption equilibrium isotherms for the four chlorophenols and phenol
      were studied and modelled for adsorption onto titanium dioxide (TiO2)
      semiconductor catalyst. Langmuir adsorption parameters were determined and used
      to calculate adsorption constant and maximum adsorption capacity. The adsorption
      of chloride phenolics onto titanium dioxide catalyst increased in the order of 4 
      CP < DCP < Ph < TCP < PCP. Photocatalytic studies analysed the efficiency of
      oxidation and found improved degradation with higher chloride substituted
      phenolics in the order of PCP > TCP > DCP >= 4 - CP. Photocatalytic parameters
      were calculated and estimated along with sensitivity and uncertainty analyses.

PMID- 26223021
TI  - Biofilms and extracellular polymeric substances mediate the transport of graphene
      oxide nanoparticles in saturated porous media.
AB  - Understanding the fate and transport of graphene oxide nanoparticles (GONPs) in
      the subsurface environments is of crucial importance since they may pose
      potential risks to the environment and human health. However, little is known
      about the significance of biofilm on mobility of GONPs in the subsurface. Here we
      investigated the transport of GONPs in saturated sand coated with Bacillus
      subtilis (Gram-positive) and Pseudomonas putida (Gram-negative) biofilms, and
      their secreted extracellular polymeric substances (EPS) under environmentally
      relevant ionic strengths (1-50mM NaCl) at pH 7.2. Our results showed that
      irrespective of bacteria type, greater retention of GONPs occurred in biofilm
      coated sand compared to clean sand, likely attributed to the increased surface
      roughness and physical straining. However, EPS showed negligible influence on
      GONPs transport, which was inconsistent with the findings in the presence of
      biofilms, while they exhibited comparable zeta-potentials. The different
      retention phenotype of GONPs in the presence of EPS was induced by hydration
      effect and steric repulsion. A two-site kinetic retention model well-described
      the transport of GONPs in porous media covered with different surface coatings,
      which proves the applicability of mathematical model in predicting nanoparticles'
      mobility in the subsurface environments, when considering the potential effects
      of biofilm and EPS. 

PMID- 26223022
TI  - Recyclable Mg-Al layered double hydroxides for fluoride removal: Kinetic and
      equilibrium studies.
AB  - Mg-Al layered double hydroxides (LDHs) intercalated with NO3(-) (NO3 . Mg-Al LDH)
      and Cl(-) (Cl . Mg-Al LDH) were found to adsorb fluoride from aqueous solutions.
      Fluoride is removed by anion exchange in solution with NO3(-) and Cl(-)
      intercalated in the LDH interlayer. In both cases, the residual F concentration
      is lower than the effluent standards for F in Japan (8 mg/L). The rate
      determining step in the removal of F using NO3 . Mg-Al and Cl . Mg-Al LDH is
      chemical adsorption involving F(-) anion exchange with intercalated NO3(-) and
      Cl(-) ions. The removal of F is described by pseudo-second-order reaction
      kinetics, with Langmuir-type adsorption. The values obtained for the maximum
      adsorption and the equilibrium adsorption constant are respectively 3.3 mmol g(
      1) and 2.8 with NO3 . Mg-Al LDH, and 3.2 mmol g(-1) and 1.5 with Cl . Mg-Al LDH.
      The F in the F . Mg-Al LDH produced in these reactions was found to exchange with
      NO3(-) and Cl(-) ions in solution. The regenerated NO3 . Mg-Al and Cl . Mg-Al
      LDHs thus obtained can be used once more to capture aqueous F. This suggests that
      NO3 . Mg-Al and Cl . Mg-Al LDHs can be recycled and used repeatedly for F
      removal.

PMID- 26223023
TI  - Contrast sensitivity revealed by microsaccades.
AB  - Microsaccades are small rapid and involuntary eye movements that occur during
      fixation in an apparently stochastic manner. They are known to be inhibited in
      response to sensory transients, with a time course that depends on the stimulus
      parameters and attention. However, the temporal precision of their onsets and the
      degree to which they can be used to assess the response of the visual system to
      basic stimulus parameters is currently unknown. Here we studied microsaccade
      response properties as a function of the contrast and spatial frequency of visual
      onsets. Observers (n = 18) viewed and silently counted 2-min sequences of Gabor
      patches presented briefly (100 ms) at 1 Hz. Contrast and spatial frequency were
      randomized in different experiments. We found that the microsaccade response
      time, as measured by the latency of the first microsaccade relative to stimulus
      onset following its release from inhibition, was sensitive to the contrast and
      spatial frequency of the stimulus and could be used to extract a contrast
      response function without the observers' response. We also found that contrast
      detection thresholds, measured behaviorally for different spatial frequencies,
      were highly and positively correlated (R = 0.87) with the microsaccade response
      time measured at high contrast (>4 times the threshold). These results show that
      different measures of microsaccade inhibition, especially the microsaccade
      response time, can provide accurate and involuntary measures of low-level visual
      properties such as contrast response and sensitivity. 

PMID- 26223024
TI  - Mesopic luminance assessed with minimally distinct border perception.
AB  - In photopic vision, the border between two fields is minimally distinct when the
      two fields are isoluminant; that is, when the achromatic luminance of the two
      fields is equal. The distinctness of a border between extrafoveal reference and
      comparison fields was used here as an isoluminance criterion under a variety of
      adaptation conditions ranging from photopic to scotopic. The adjustment was done
      by trading off the amount of blue against the amount of red in the comparison
      field. Results show that isoluminant border settings are linear under all
      constant adaptation conditions, though varying with state of adaptation. The
      relative contribution of rods and cones to luminance was modeled such that the
      linear sum of the suitably weighted scotopic and photopic luminance is constant
      for the mesopic isoluminant conditions. The relative weights change with adapting
      intensity in a sigmoid fashion and also depend strongly on the position of the
      border in the visual field. 

PMID- 26223025
TI  - Orientation perception anisotropies indicate functional segregation within the
      color system.
AB  - When stimuli are luminance-defined, the visual system is known to prefer those
      that are radially oriented with respect to the point of fixation over
      tangentially oriented ones (the radial bias effect). In two contrast detection
      experiments and an orientation discrimination experiment, we investigated whether
      the radial bias effect also exists for chromatic stimuli. The contrast detection
      experiments revealed the radial bias effect to be color-specific; the effect was
      present for isoluminant red-green stimuli but absent or in the opposite direction
      for blue-yellow stimuli with, respectively, low (0.4 c/ degrees ) and medium (1
      c/ degrees ) spatial frequencies. In agreement with previous results, we also
      found distinct sensitivity distributions for red-green and blue-yellow signals as
      a function of eccentricity. The results, thus, demonstrate a functional
      segregation between red-green and blue-yellow signals not only in local but also
      in nonlocal signal processing. 

PMID- 26223026
TI  - Transparent surface segregation enables visual feature binding in rapidly
      alternating displays.
AB  - Visual feature binding-the mechanism by which our typically coherent and unified
      perceptual experience arises from distributed neural representations-is the
      source of much intrigue in the neuroscience of perception. Surprisingly, feature
      binding can occur in rapidly alternating displays of color-orientation
      combinations (e.g., rightward-orange, leftward-blue). However, we found that when
      the angular separation between orientations is reduced, binding is selectively
      impaired at temporal alternation frequencies around 5 Hz. To isolate the
      mechanisms involved, we devised a novel display in which color-orientation
      conjunction information was distributed temporally over two checkered stimuli and
      was perceptually discriminable only within an intermediate range of temporal
      frequencies (7.5-15 Hz). We propose that accurate color-orientation judgments at
      frequencies exceeding 5 Hz depend on the rapid formation of persistent surface
      representations that can be accessed by binding mechanisms, circumventing the
      latter's relatively low temporal resolution. 

PMID- 26223027
TI  - About-face on face recognition ability and holistic processing.
AB  - Previous work found a small but significant relationship between holistic
      processing measured with the composite task and face recognition ability measured
      by the Cambridge Face Memory Test (CFMT; Duchaine & Nakayama, 2006).
      Surprisingly, recent work using a different measure of holistic processing
      (Vanderbilt Holistic Face Processing Test [VHPT-F]; Richler, Floyd, & Gauthier,
      2014) and a larger sample found no evidence for such a relationship. In
      Experiment 1 we replicate this unexpected result, finding no relationship between
      holistic processing (VHPT-F) and face recognition ability (CFMT). A key
      difference between the VHPT-F and other holistic processing measures is that
      unique face parts are used on each trial in the VHPT-F, unlike in other tasks
      where a small set of face parts repeat across the experiment. In Experiment 2, we
      test the hypothesis that correlations between the CFMT and holistic processing
      tasks are driven by stimulus repetition that allows for learning during the
      composite task. Consistent with our predictions, CFMT performance was correlated
      with holistic processing in the composite task when a small set of face parts
      repeated over trials, but not when face parts did not repeat. A meta-analysis
      confirms that relationships between the CFMT and holistic processing depend on
      stimulus repetition. These results raise important questions about what is being
      measured by the CFMT, and challenge current assumptions about why faces are
      processed holistically. 

PMID- 26223028
TI  - Body Mass Index and Waistline are Predictors of Survival for Hepatocellular
      Carcinoma After Hepatectomy.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers
      worldwide especially in China. This article aimed to evaluate the influence of
      body mass index (BMI) and waistline on complications, postoperative death, and
      long-term survival in patients undergoing surgery for HCC. MATERIAL AND METHODS:
      136 patients were enrolled and divided into 4 groups: group A, BMI <25; group B,
      BMI >=25; group C, waistline <90 cm in males or waistline <80 cm in females;
      group D, waistline >=90 cm in males or waistline >=80 cm in females. Clinical
      pathological features and surgical outcomes of these patients were analyzed
      retrospectively. RESULTS: There were no significant differences in postoperative
      complication rate and postoperative death between group A and group B, although
      pulmonary infection showed a significant difference between 2 groups (P=0.017).
      Vascular invasion, waistline, and BMI are the independent prognostic factors for
      long-term survival. The disease-free survival curves after hepatectomy showed no
      statistically significant difference between group A and group B. Group C had the
      better overall survival than group D, and group A had the better overall survival
      than group B. CONCLUSIONS: BMI and waistline are both independent prognostic
      factors for long-term survival of HCC after hepatectomy. Waistline is more
      important than BMI in predicting the disease-free survival of HCC after
      hepatectomy.

PMID- 26223029
TI  - Cervical cytological screening: Assessment of the Fournier (r) self-sampling
      device in a cervical pathology outpatient clinic.
AB  - BACKGROUND: The objective of this study was to investigate the performance of the
      Fournier((r)) self-sampled device in the cytological diagnosis of cervical
      precursor or neoplastic lesions. The colposcopy and cervical biopsy were used as
      the gold standard evaluation. METHOD: This was a case-control study performed at
      a cervical pathology outpatient clinic from January 2008 to October 2009. Samples
      were obtained through physician-collected mode before a colposcopic evaluation.
      Liquid-based cytology slides obtained with the device in question were stained
      using the Papanicolaou method and anti-p16 immunocytochemistry and were analyzed
      by two pathologists blind to the histological and colposcopic diagnoses. RESULTS:
      Diagnostic performance for Fournier device using Papanicolaou technique was
      sensitivity 41.1% (Pathologist 1-P1) and 52.9% (Pathologist 2-P2) for diagnosing
      low-grade intraepithelial lesions; for high-grade lesions and cervical cancer,
      sensitivity was 68.7% (P1) and 75.0% (P2) and specificity was 81.8% (P1) and
      73.8% (P2). When using the anti-p16 immunocytochemistry, the sensitivity for
      diagnosing low-grade intraepithelial lesions was 57.1% (P1) and 62.9% (P2), and
      the sensitivity was 87.5% (P1) and 93.8% (P2) for high-grade lesions and cancer.
      The specificity was 75.0% (P1) and 54.4% (P2). CONCLUSIONS: These results show
      that when used with "blind" physician-collected cytology in an outpatient
      setting, the Fournier((r)) device achieved a sensitivity and specificity
      comparable to those obtained by the Pap test traditionally collected during a
      speculum examination.

PMID- 26223030
TI  - Extracellular aromatic biosurfactant produced by Tsukamurella pseudospumae and T.
      spumae during growth on n-hexadecane.
AB  - Biosurfactants are surface-active agents produced by microorganisms and show
      increasing significance in various industrial applications. A great variety of
      these secondary metabolites are described to occur within actinomycetes, amongst
      trehalose lipids and oligosaccharide lipids produced by the family
      Tsukamurellaceae. This study reports on the production of not yet described
      compounds with surface active behavior by non-pathogenic Tsukamurella
      pseudospumae and Tsukamurella spumae during growth on hydrophobic carbon sources.
      Extracts of the purified compounds differ in terms of structure and performance
      properties to other biosurfactants described within their family. Infrared and
      nuclear magnetic resonance spectroscopic analysis revealed the presence of
      aromatic moieties within the surfactant produced, which to date is only known to
      occur within phenolic glycolipids of some mycobateria. 

PMID- 26223031
TI  - Genetic analysis of 17 Y-STR loci in Han population from Gansu province,
      northwestern China.

PMID- 26223034
TI  - Special feature.  Year in review 2011.

PMID- 26223032
TI  - LINE-1 DNA methylation: A potential forensic marker for discriminating
      monozygotic twins.
AB  - Discriminating individuals within a pair of monozygotic (MZ) twins using genetic
      markers remains unresolved. This inability causes problems in criminal or
      paternity cases involving MZ twins as suspects or alleged fathers. Our previous
      study showed DNA methylation differences in interspersed repeat sequences such as
      Alu and LINE-1 within pairs of newborn MZ twins. To further evaluate the possible
      value of LINE-1 DNA methylation for discriminating MZ twins, this study
      investigated the LINE-1 DNA methylation of a large number of twins. We collected
      blood samples and buccal cell samples from 119 pairs of MZ and 57 pairs of
      dizygotic (DZ) twins. Genomic DNA was extracted and LINE-1 methylation level was
      detected using bisulfite pyrosequencing. The mean methylation level of the three
      CpG sites in the blood sample among the 176 unrelated individuals was 76.60% and
      70.08% in buccal samples. This difference was significant, indicating the tissue
      specificity of LINE-1 DNA methylation. Among 119 pairs of MZ twins, 15 pairs
      could be discriminated according to the difference of CpG methylation level
      between them, which accounted for 12.61% of total number of MZ pairs. As for DZ
      twins, 10 pairs had significant differences between two individuals, which
      accounted for 17.54% of the total 57 DZ pairs. In conclusion, there are global
      DNA methylation differences within some healthy concordant monozygotic (MZ) twin
      pairs. LINE-1 DNA methylation might be a potential marker for helping to
      discriminate individuals within MZ twin pairs, and the tissue specificity must be
      considered in practice. 

PMID- 26223033
TI  - Individualized feedback during simulated laparoscopic training:a mixed methods
      study.
AB  - OBJECTIVE: This study aimed to explore the value of individualized feedback on
      performance, flow and self-efficacy during simulated laparoscopy. Furthermore, we
      wished to explore attitudes towards feedback and simulator training among medical
      students. METHODS: Sixteen medical students were included in the study and
      randomized to laparoscopic simulator training with or without feedback. A teacher
      provided individualized feedback continuously throughout the procedures to the
      target group. Validated questionnaires and scales were used to evaluate self
      efficacy and flow. The Mann-Whitney U test was used to evaluate differences
      between groups regarding laparoscopic performance (instrument path length), self
      efficacy and flow. Qualitative data was collected by group interviews and
      interpreted using inductive thematic analyses. RESULTS: Sixteen students
      completed the simulator training and questionnaires. Instrument path length was
      shorter in the feedback group (median 3.9 m; IQR: 3.3-4.9) as compared to the
      control group (median 5.9 m; IQR: 5.0-8.1), p<0.05. Self-efficacy improved in
      both groups. Eleven students participated in the focus interviews. Participants
      in the control group expressed that they had fun, whereas participants in the
      feedback group were more concentrated on the task and also more anxious. Both
      groups had high ambitions to succeed and also expressed the importance of getting
      feedback. The authenticity of the training scenario was important for the
      learning process. CONCLUSIONS: This study highlights the importance of
      individualized feedback during simulated laparoscopy training. The next step is
      to further optimize feedback and to transfer standardized and individualized
      feedback from the simulated setting to the operating room.

PMID- 26223035
TI  - HIV treatment as prevention--the time is now.

PMID- 26223036
TI  - Antiretroviral pre-exposure prophylaxis; new hope and conundrums.

PMID- 26223037
TI  - Economic factors hamper HIV control efforts.

PMID- 26223038
TI  - Clarity on when to start ART in active TB.

PMID- 26223039
TI  - New HCV treatments look promising for HIV/HCV-coinfected patients.

PMID- 26223040
TI  - HIV continues to target young black MSM ...and syphilis isn't far behind.

PMID- 26223041
TI  - Cure: no longer a four-letter word in HIV research.

PMID- 26223042
TI  - When to start ART in asymptomatic patients.

PMID- 26223043
TI  - Growing the intense inhibitor class--Elvitegravir and Dolutegravir.

PMID- 26223044
TI  - Rilpivirine arrives--with caveats.

PMID- 26223046
TI  - HIV-related immune activation and non-AIDS-related complications: story unfolds.

PMID- 26223045
TI  - NRTI-sparing regimens continue to disappoint.

PMID- 26223047
TI  - Ground Truth for Diffusion MRI in Cancer: A Model-Based Investigation of a Novel
      Tissue-Mimetic Material.
AB  - This work presents preliminary results on the development, characterisation, and
      use of a novel physical phantom designed as a simple mimic of tumour cellular
      structure, for diffusion-weighted magnetic resonance imaging (DW-MRI)
      applications. The phantom consists of a collection of roughly spherical, micron
      sized core-shell polymer 'cells', providing a system whose ground truth
      microstructural properties can be determined and compared with those obtained
      from modelling the DW-MRI signal. A two-compartment analytic model combining
      restricted diffusion inside a sphere with hindered extracellular diffusion was
      initially investigated through Monte Carlo diffusion simulations, allowing a
      comparison between analytic and simulated signals. The model was then fitted to
      DW-MRI data acquired from the phantom over a range of gradient strengths and
      diffusion times, yielding estimates of 'cell' size, intracellular volume fraction
      and the free diffusion coefficient. An initial assessment of the accuracy and
      precision of these estimates is provided, using independent scanning electron
      microscope measurements and bootstrap-style simulations. Such phantoms may be
      useful for testing microstructural models relevant to the characterisation of
      tumour tissue.

PMID- 26223048
TI  - Multiple Orderings of Events in Disease Progression.
AB  - The event-based model constructs a discrete picture of disease progression from
      cross-sectional data sets, with each event corresponding to a new biomarker
      becoming abnormal. However, it relies on the assumption that all subjects follow
      a single event sequence. This is a major simplification for sporadic disease data
      sets, which are highly heterogeneous, include distinct subgroups, and contain
      significant proportions of outliers. In this work we relax this assumption by
      considering two extensions to the event-based model: a generalised Mallows model,
      which allows subjects to deviate from the main event sequence, and a Dirichlet
      process mixture of generalised Mallows models, which models clusters of subjects
      that follow different event sequences, each of which has a corresponding
      variance. We develop a Gibbs sampling technique to infer the parameters of the
      two models from multi-modal biomarker data sets. We apply our technique to data
      from the Alzheimer's Disease Neuroimaging Initiative to determine the sequence in
      which brain regions become abnormal in sporadic Alzheimer's disease, as well as
      the heterogeneity of that sequence in the cohort. We find that the generalised
      Mallows model estimates a larger variation in the event sequence across subjects
      than the original event-based model. Fitting a Dirichlet process model detects
      three subgroups of the population with different event sequences. The Gibbs
      sampler additionally provides an estimate of the uncertainty in each of the model
      parameters, for example an individual's latent disease stage and cluster
      assignment. The distributions and mixtures of sequences that this new family of
      models introduces offer better characterisation of disease progression of
      heterogeneous populations, new insight into disease mechanisms, and have the
      potential for enhanced disease stratification and differential diagnosis.

PMID- 26223049
TI  - Ask the doctor. Is there something to relieve severe neuropathy in someone's
      feet?

PMID- 26223050
TI  - Best ways to manage stress.  Goal setting and relaxation techniques reduce stress
      and ease the physical and emotional burden it can take.

PMID- 26223051
TI  - Does better gum health protect your heart?  Gum disease is associated with
      coronary heart disease.

PMID- 26223052
TI  - Quick-start strength-training program.  Work out at home or in your office to
      improve muscle mass.

PMID- 26223053
TI  - Fight inflammation with food.  Give your body protection with fiber, good fats,
      whole grains, and omega-3s.

PMID- 26223054
TI  - Is that noise pollution, or are you hard of hearing?  A loss of volume and
      clarity can interfere with your ability to understand conversations.

PMID- 26223055
TI  - Staying healthy while using PPIs.  Be mindful of risks for fracture, low B12, and
      a spike in stomach acid.

PMID- 26223056
TI  - Whole grains associated with longevity, say Harvard researchers.

PMID- 26223057
TI  - New concerns about anticholinergic medications.

PMID- 26223058
TI  - U.S. Dental School Deans' Perceptions of   the Rising Cost of Dental Education
      and   Borrowing Pressures on Dental Students:   Report of Survey Results.
AB  - This report presents findings from a survey of U.S. dental school deans designed
      to capture their perceptions regarding the rising cost of dental education and
      its impact on borrowing by dental students to finance their education. The survey
      included questions about factors influencing the cost of dental education,
      concerns about dental student borrowing, and financial awareness resources for
      students. The survey was distributed to the deans of all 63 U.S. dental schools
      in January 2013; 42 deans responded, for a 67% response rate. The results
      indicate that, according to the responding deans, new clinical technologies,
      technology costs, and central university taxes are the main factors that
      contribute to the increasing cost of dental education. Coupled with reduced state
      appropriations at public dental schools and declines in private giving at all
      dental schools, dental school deans face a perplexing set of financial management
      challenges. Tuition and fees are a primary source of revenue for all dental
      schools; however, many deans do not have total control over the cost of attending
      their schools since tuition and fees are often tied to mandates and policies from
      the parent university and the state legislature. The findings of this study
      indicate that U.S. dental school deans are aware of and concerned about the
      impact of increases in tuition and fees on dental student debt and that they are
      using a variety of strategies to address the growth in dental student borrowing.

PMID- 26223059
TI  - THORACIC INVOLVEMENT IN CONNECTIVE TISSUE DISEASES: RADIOLOGICAL PATTERNS AND
      FOLLOW-UP.
AB  - Connective tissue diseases (CTDs) are a heterogeneous group of idiopathic
      inflammatory diseases involving various organs. A thoracic involvement is
      frequent, and chest-CT represents the imaging technique of reference in its
      assessment. Pulmonary abnormalities related to CTDs are various; although several
      disease-specific aspects have been described, the two most clinically relevant
      complications are represented by interstitial lung disease and pulmonary arterial
      hypertension. The early identification of a thoracic involvement, with the
      adoption of specific therapies, can significantly change patient's prognosis. The
      aim of this article is to review the most common typical and atypical CT features
      of thoracic involvement occurring in CT, especially focusing on interstitial lung
      disease.

PMID- 26223060
TI  - THE EFFICIENCY OF ULTRASOUND ELASTOGRAPHY IN THE DIFFERENTIAL DIAGNOSIS OF
      THYROID NODULES.
AB  - AIM: To evaluate the efficiency of ultrasound elastography (USE) in the
      differential diagnosis of thyroid nodules. METHODS: One hundred thyroid nodules
      in 100 patients (79 females, 21 males, age range 18-78; mean age = 45.6 years)
      were evaluated with real-time freehand USE, using Hitachi EUB 7500 equipment and
      elasticity scores were obtained. The elasticity was scored as follows: Score 1,
      elasticity in the entire nodule; Score 2, mainly elastic nodule with the presence
      of inelastic areas not constant during real time examination; Score 3, constant
      inelastic areas prevalently arranged at the periphery of the nodule; Score 4,
      constant inelastic areas prevalently arranged at the center of the nodule; Score
      5, no elasticity in the nodule. Also mean strain ratio values were calculated for
      all nodules. RESULTS: Eighty-four (86%) of cases were benign and sixteen (16%)
      were malignant. Elasticity score 3 and higher and strain ratio higher than 2.485
      had statistically significant relation with malignancy (p < 0.05). CONCLUSIONS:
      USE including strain ratio calculations besides subjective evaluation of
      elasticity scores is an efficient imaging method which may contribute to the
      differential diagnosis of thyroid nodules.

PMID- 26223061
TI  - GASTROINTESTINAL COMPLICATIONS OF ACCIDENTAL INGESTION OF FOREIGN OBJECTS.
AB  - Ingestion of foreign objects is common and most of the time, they pass without
      major problems. However sometimes they could cause significant morbidity or even
      mortality. Most of the time they cause pain in the pharyngeal or oesophageal
      area. In these instants, diagnosing the problem is straightforward, limiting the
      use of radiographic diagnosis. However the intraperitoneal complications include
      stomach or bowel perforation, obstruction, abscedation, septicemia or even
      hemorrhage or thrombosis of the abdominal veins. Because of the considerable
      risks, accompanied by the accidental ingestion of a metallic object, the
      preferred technique for screening is still Computed Tomography. However not all
      of these objects are radio-opaque and therefore could not always be diagnosed
      radiographically. In this article we will describe several cases of
      complications, due to the accidental ingestion of foreign objects. Also we will
      describe certain patient related risk factors significantly increasing, not only
      the amount, but also the severity of those complications. Diverticulosis seems
      the most common risk factor amongst the patients described and so it could be one
      of the more common triggers causing (recidivating) diverticulitis attacks. But
      because not all of the ingested foreign objects are radiopaque or still in the
      gastrointestinal tract, such a theory is difficult to prove.

PMID- 26223062
TI  - A GIANT RETROPERITONEAL LIPOMA PRESENTING AS A SCIATIC HERNIA: MRI FINDINGS.
AB  - Sciatic hernia is a rare condition and its clinical diagnosis is uneasy.
      Herniation of pelvic organs as well as of retroperitoneal neoplasm has been
      reported in the literature. Sciatica occurs as a result of compression of the
      sciatic nerve by the herniated sac. We present a case of retroperitoneal lipoma
      in a patient who had lower leg complaint and describe the imaging findings.

PMID- 26223063
TI  - PSEUDOTUMORAL TOPHACEOUS INVOLVEMENT OF THE ACHILLES PARATENON.
AB  - Gout is the most common form of microcrystalline arthropathy which usually does
      not pose a diagnostic challenge when patients have typical presentation,
      appropriate biochemical picture and classical radiographic appearance. However,
      formation of gouty tophi in unusual locations and with atypical presentations may
      mislead clinicians and radiologists, thereby justifying gout nickname as the
      "great mimicker". When interpreting images of tendon related masses, radiologists
      should be aware of gouty tophi as a possible differential given its variable and
      nonspecific imaging appearance. In this article, we present a case of a patient
      with a painless tophaceous gout nodule, adjacent to the Achilles tendon.

PMID- 26223064
TI  - REPORT OF A RARE ANATOMIC VARIANT: LEFT UPPER LOBE PARTIAL ANOMALOUS PULMONARY
      VENOUS RETURN.
AB  - We report the CT findings in a case of partial anomalous pulmonary venous return
      (PAPVR) from the left upper lobe in an adult. PAPVR is an anatomic variant in
      which one to three pulmonary veins drain into the right atrium or its
      tributaries, rather than into the left atrium. This results in a left-to-right
      shunt with varying clinical presentation. These can range from asymptomatic
      patients to advanced cardiac failure.

PMID- 26223065
TI  - ISCHIOFEMORAL IMPINGEMENT DUE TO A SOLITARY EXOSTOSIS.
AB  - Ischiofemoral impingement is a rare cause of hip pain related to narrowing of the
      space between the ischial tuberosity and the lesser trochanter. It is usually
      seen in middle-aged women. We report a rare case of a young male patient
      presenting with ischiofemoral impingement due to a solitary exostosis at the
      lesser trochanter. Imaging, especially Magnetic Resonance Imaging (MRI), is an
      excellent tool to confirm the diagnosis by demonstrating narrowing of the
      ischiofemoral space and soft tissue edema in the muscle belly of the quadratus
      femoris muscle.

PMID- 26223066
TI  - MACRODYSTROPHIA LIPOMATOSA WITH ULNAR DISTRIBUTION IN HAND: MR EVALUATION OF A
      RARE DISORDER.
AB  - Macrodystrophia lipomatosa is a rare, non-hereditary congenital anomaly
      characterized by localised gigantism in the form of macrodactyly affecting a part
      of limb and rarely entire limb due to overgrowth of all mesenchymal elements.
      Radiological and pathological hallmark is the disproportionate fibroadipose
      tissue proliferation in subcutaneous tissue, nerve sheaths, and periosteum that
      lead to soft tissue and bony enlargement. We present the case of a twenty years
      old female who presented with history of gradual enlargement of the medial aspect
      of right hand along ulnar nerve distribution since birth. MRI showed hypertrophy
      of bones and soft tissue with fatty proliferation, leading to the diagnosis of
      macrodystrophia lipomatosa.

PMID- 26223067
TI  - OSTEOCHONDROMA OF THE PROXIMAL HUMERUS WITH FRICTIONAL BURSITIS AND SECONDARY
      SYNOVIAL OSTEOCHONDROMATOSIS.
AB  - We report a case of multiple hereditary exostosis in a 33-year old patient with
      clinical symptoms of pain and impression of a growing mass of the left shoulder
      alerting potential risk of malignant transformation of an osteochondroma. Imaging
      studies illustrated perilesional bursitis surrounding an osteochondroma of the
      proximal humerus. Malignant transformation was excluded with MRI. Fragments of
      the osteochondroma were dislocated in the inflammatory synovial bursa
      illustrating a case of secondary synovial osteochondromatosis.

PMID- 26223068
TI  - CARDIAC AMYLOIDOSIS DIAGNOSED ON MRI.
AB  - The frequency of cardiac involvement varies among other types of amyloidosis.
      Cardiac amyloidosis leads to systolic and diastolic dysfunction with symptoms of
      heart failure. Cardiac magnetic resonance (CMR) findings are helpful in
      supporting the diagnosis of amyloid cardiomyopathy. We report a case of a 73-year
      old man who presented with shortness of breath. Echocardiography showed a
      hypertrophic, diffusely hypocontractile left ventricle with a restrictive filling
      pattern. The diagnosis of an isolated amyloidosis was made on CMR.

PMID- 26223069
TI  - Gaucher disease presenting with vertebral compression fractures and vertebral
      osteonecrosis.

PMID- 26223070
TI  - Combination of unusual lesions after blunt trauma.

PMID- 26223071
TI  - Umbilical artery pseudoaneurysm.

PMID- 26223072
TI  - Extrapulmonary manifestation of lymphangioleiomyomatosis.

PMID- 26223073
TI  - Arachnoidal cyst arising from the oculomotor cistern.

PMID- 26223074
TI  - Contribution of color Doppler sonography to the characterization of an unusual
      thickening of the common bile duct.

PMID- 26223075
TI  - Foix-Chavany-Marie or opercular syndrome.

PMID- 26223076
TI  - Sclerosing hemangioma of the lung.

PMID- 26223077
TI  - Progressive quadriplegia resulting from septic facet joint arthritis.

PMID- 26223078
TI  - Serpiginous cholesteatoma mimicking a vascular channel.

PMID- 26223079
TI  - A rare case of ischemic stroke following occlusion of the artery of Percheron.

PMID- 26223080
TI  - Preface. What's New in Autoimmunity: New Autoantibodies, New Therapies, New
      Diseases.

PMID- 26223081
TI  - In The Beginning.

PMID- 26223083
TI  - Small-Medium Vessel Vasculitides: is the Complement System a Potential Forgotten
      Target?
AB  - Systemic vasculitides are a group of uncommon diseases characterized by blood
      vessel inflammation. The complement system is involved in the pathogenesis and
      clinical manifestations of several autoimmune diseases, including systemic
      vasculitides. This enzymatic system is a component of the innate immune system.
      Its main function was initially believed to be limited to the recognition and
      elimination of pathogens, but research in recent years has demonstrated the
      important role that complement proteins play in modulating adaptive immunity and
      in bridging innate and adaptive responses. Its activation is also critical for
      the development of T cell immunity and natural antibodies as well as for the
      regulation of autoreactive B cells. In systemic vasculitides, particularly small
      medium vesselvasculitides, the complement system has been shown to contribute to
      the development of inflammatory damage. In view of these crucial functions, the
      complement system represents an attractive therapeutic target for a wide range of
      diseases. including vasculitic disorders.

PMID- 26223082
TI  - Vitamin D Antibodies in Systemic Sclerosis Patients: Findings and Clinical
      Correlations.
AB  - BACKGROUND: Vitamin D is a pivotal factor in calcium homeostasis and exerts
      immunomodulatory effects. Hypovitamin D has been demonstrated in systemic
      sclerosis (SSc) patients and may be related to more severe disease of longer
      duration and with extensive skin involvement. OBJECTIVES: To seek anti-vitamin D
      antibodies in SSc patients, as found by previous research in patients with
      systemic lupus erythematosus (SLE). METHODS: The study included 54 SSc patients
      and 41 volunteers. Immunoglobulin (Ig) G and IgM autoantibody levels against
      25(OH)D and 1,25(OH)D were obtained from patients and controls and were compared.
      SSc patients were assessed for autoantibody profile and disease severity.
      RESULTS: Vitamin D antibodies were present in 87% of SSc patients and 42% of
      controls. Higher levels of anti-25(OH)D IgM antibodies were detected in SSc
      patients compared to controls (0.48 +/- 0.22 vs. 0.29 +/- 0.29, respectively, P =
      0.002); however, IgG levels were lower in the SSc patients. No such
      discriminative. effect was found regarding anti-1,25(OH)D antibodies between SSc
      and controls. No correlation was found between,vitamin D antibodies and other
      autoantibodies, disease severity, or target organ damage. CONCLUSIONS: To the
      best of our knowledge; this is the first study of these novel, anti-vitamin D
      antibodies in SSc patients and the first time a correlation between IgM 25(OH)
      vitamin D antibodies and scleroderma has been identified. Further research on the
      pathophysiological significance and therapeutic potential of vitamin D is
      required.

PMID- 26223084
TI  - Interleukin-1: Ariadne's Thread in Autoinflammatory and Autoimmune Disorders.
AB  - Autoinflammatory and autoimmune disorders are characterized by chronic activation
      of the immune system, which leads to systemic self-directed inflammation in
      genetically predisposed individuals. Mutations in inflammasome-related proteins
      have been associated with autoinflammatory disorders, and the link between
      inflammasome and autoimmune disorders is becoming increasingly clear. As
      researchers learn more about these two areas, other disorders that were once
      thought to be autoimmune are now being considered autoinflammatory, or as having
      at least an autoinflammatory component. This review depicts the role of
      interleukin-1 as "Ariadne's thread" on the path through the labyrinth of
      autoinflammatory and autoimmune disorders and emphasizes the blurred boundary
      between innate and adaptive immune systems.

PMID- 26223085
TI  - Is B Cell-Targeted Therapy Effective in Systemic Lupus Erythematosus?
AB  - In the past decade we have witnessed a dramatic change in the management of
      autoimmune diseases, such as rheumatoid arthritis, due to the development of new
      biologic drugs designed to target key mediators in the autoimmune process.
      However, the development of similar target-specific drugs for the management of
      SLE has not been as successful. The B cell has long been considered central to
      the pathogenesis of SLE and has been regarded as an important target for biologic
      drugs. Several B cell-targeted drugs have been developed and although the
      mechanisms seem promising, most of the studies published to date have failed to
      achieve their primary endpoints, leading to an ongoing debate regarding the role
      of B cell therapy in SLE. The present report discusses the pros and cons of B
      cell-targeted therapy in SLE, reviews the clinical studies, and offers possible
      explanations forthe discrepancies between randomized control studies and real
      life experience.

PMID- 26223086
TI  - Livedo Reticularis: An Enigma.
AB  - Livedo reticularis is a common cutaneous manifestation of APS and may be a
      prognostic marker of more severe disease. It is associated with arterial and
      venous thrombosis and pregnancy morbidity irrespective of the presence of
      antiphospholipid antibodies. Recent results suggest the possibility of an
      association with accelerated atherosclerosis in patients with livedo. Given the
      similarities between APS and livedo (aPL negative), experts in this field believe
      that livedo may represent the so-called seronegative antiphospholipid syndrome,
      although the exact relationship of livedo with seronegative APS remains to be
      elucidated. LV may present as painful cutaneous ulcers that are often difficult
      to treat. The underlying pathology involves prothrombotic as well as
      immunological processes with some overlap with APS. Treatment remains challenging
      and results are often variable.

PMID- 26223087
TI  - New Autoantibodies in Inflammatory Myopathies: Diagnostic Value and Relationship
      with Clinical Phenotypes.

PMID- 26223088
TI  - New Therapeutic Approaches to Anti-Neutrophil Cytoplasmic Antibody-Associated
      Vasculitides: Looking at Tomorrow.

PMID- 26223089
TI  - Tumor Necrosis Factor-Alpha at the Crossroad between Rheumatoid Arthritis and
      Autoimmune Cholangitis.

PMID- 26223090
TI  - Successful Etanercept Treatment for Primary Biliary Cirrhosis Associated with
      Rheumatoid Arthritis.

PMID- 26223091
TI  - Autoimmune Pitfalls of Anti-Tumor Necrosis Factor-Alpha Therapy.

PMID- 26223092
TI  - Transverse Myelitis Activation Post-H1N1 Immunization: A Case of Adjuvant
      Induction?

PMID- 26223093
TI  - What to do when the Diagnosis of Giant Cell Arteritis and Takayasu's Arteritis
      Overlap.

PMID- 26223094
TI  - Digital Ulcers, Systemic Sclerosis Sine Scleroderma and Paraneoplastic Phenomena
      Responding to Bosentan Therapy.

PMID- 26223095
TI  - Immune Mediated Myopathy following Long-Term Statin Therapy.

PMID- 26223096
TI  - Etanercept-Induced Pneumonitis: Severe Complication of Tumor Necrosis Factor
      Alpha Blocker Treatment.

PMID- 26223097
TI  - Infighting over Obamacare Within the GOP and More Challenges for State Health
      Exchanges.

PMID- 26223098
TI  - Four Ways to Avoid a Credentialing Cash Flow Crisis.
AB  - Credentialing a physician for Medicare and private plans is a detailed and time
      consuming process, but it must be completed before a plan will reimburse a
      practice's billed services. Assign a person with the right skills for this
      project, and insist on regular progress reports to be certain credentialing has
      been successfully completed. Submit credentialing applications three to six
      months ahead of opening your practice doors, moving to a new location, or merging
      with another organization. If you're considering outsourcing the credentialing
      process to a service, verify its reputation and work products with its customers.

PMID- 26223099
TI  - The Value of Physician Leaders to Nonphysician Coworkers.
AB  - With few exceptions, physician leaders are perceived as valuable to their
      organizations, helping to define goals, set priorities, and plan future
      direction. In some cases, however, physician leaders are misunderstood or
      devalued by senior business leaders. There could be several reasons for this
      observation: (1) the roles and responsibilities of physician leaders may be
      unclear to business leaders; (2) nonmedical leaders may question the business
      relevance of the activities performed by physician leaders; and (3) some business
      executives may believe (erroneously) that the activities performed by physician
      leaders are nonessential, or could be performed equally well by lesser trained
      healthcare professionals. Under such circumstances, physicians may become
      demoralized and indignant, but they should never lose sight of their importance
      to the everyday coworkers who are the most valuable asset of any organization.

PMID- 26223100
TI  - Developing Composite Quality Measures for EHR-Enabled Primary Care Practices in
      New York City.
AB  - We describe the process of developing composite quality measures (CQMs). During
      the initial consultative process, we grouped quality measures based on the
      associated clinical workflow and difficulty, and then confirmed the groupings
      with factor analysis. The CQMs are estimated as the mean of the measures for each
      group. We used analysis of variance followed by a post hoc analysis to assess:
      (1) performance among the different CQMs each year; and (2) the performance trend
      for each of the composite measures from 2009 to 2011. The four CQMs were Control
      BP, Control-Other, Assessment, and Screening. Performance was highest at baseline
      for Control-BP (58%, SD 15.07), followed by Control-Other (48.04%, SD 22.75),
      Screening (46.49%, SD 20.21), and Assessment (42.15%, SD 19.08). Performance on
      the CQMs increased significantly with time, whereas the gap between the CQMs
      decreased significantly over time. The CQMs reflect the clinical care domains,
      and practice performance is influenced by electronic health record functionality,
      clinician workflow, and clinical difficulty.

PMID- 26223101
TI  - Being Mindful in Your Practice.
AB  - As physician practices function to deliver safe and low-risk patient care, they
      often are susceptible to unexpected events for which the consequences can be
      high. By acting mindfully, physicians can focus on better managing unexpected
      events as well as decreasing the risk of such an event. There are five main
      components of mindfulness that can be implemented within your practice to gain a
      deeper understanding of your own systems in order to become a safer practice:
      sensitivity to operations; reluctance to simplify; preoccupation with failure;
      deference to expertise; and commitment to resilience. Each component is critical
      in the prevention of both unexpected events and complacency.

PMID- 26223102
TI  - Keeping Your Practice Healthy in the Aftermath of a Disaster.

PMID- 26223103
TI  - Evaluation of Practice Tools for Asthma and Cough in Primary Care: A Knowledge-to
      Action Perspective.
AB  - Asthma and cough are two common chronic conditions whose incidence could be
      reduced with appropriate prevention and treatment measures. Practice tools can be
      effective in helping to translate emerging research evidence into clinical
      practice. This study assesses the extent to which two asthma and cough practice
      tools are used in primary care. Thirty-six primary care physicians completed a
      questionnaire on the use, usefulness, and relevance of the two tools, and
      identified barriers to their use. Results show that the tools are seldom used,
      even though physicians find them useful and adapted to their practice. Time
      constraints are the primary barrier to use, followed by a lack of organizational
      resources. Findings from the study will inform the continued development of
      effective knowledge transfer tools that are aligned with the specific practice
      contexts of primary care physicians.

PMID- 26223104
TI  - Management in Ambulance Services: Communicative Challenges.
AB  - Managers in ambulance services face many communicative challenges in their
      interaction with employees working as paramedics in prehospital medical
      practices. This series of three articles will focus on some of these challenges.
      This first article clarifies the context of manager-employee communication in
      ambulance work. The second article will present a study of how supervising
      ambulance managers and paramedics communicate, and the third will discuss how
      this communication can be improved. All the articles accentuate the same general
      point: organizational performance in prehospital medical practice depends on
      successful communication between managers and paramedics.

PMID- 26223105
TI  - Employee Records: What to Keep, How to Keep, and When to Shred.
AB  - Offices receive, generate, and maintain an inordinate volume of documents related
      to employees. Office managers, supervisors, and human resource professionals are
      always looking for ways to clear the clutter in what are often overcrowded
      administrative desks and records areas. While most are well versed in the various
      legal requirements concerning maintenance and destruction of patient records,
      there also are a myriad of laws that cover confidential information and records
      of employees. It is important for those in charge of maintaining such records to
      know what to keep, where to keep it, and for how long.

PMID- 26223106
TI  - Comparison of Healthcare Quality Outcomes Between Accountable Care Organizations
      and Physician Group Practices.
AB  - Accountable Care Organizations (ACOs) were created under the Affordable Care Act
      to deliver better quality of care at reduced cost compare with the traditional
      fee-for-service model. But their effectiveness in achieving healthcare quality
      metrics is unclear. We analyzed ACO and physician group practice (PGP)
      performance rates for the single coronary artery disease measure and four
      diabetes mellitus measures now publicly reported on the Medicare Physician
      Compare Web site for program year 2012. There was no statistically significant
      difference in reported quality measures between ACOs and PGPs. Our study shows
      that PGPs can achieve outcomes at par with ACOs.

PMID- 26223107
TI  - Adventurous Leadership for a New Year.

PMID- 26223108
TI  - Rules and Incentives: The Problem with American Healthcare.
AB  - There are very few within or outside of the American healthcare system who would
      argue that the current system of providing healthcare is badly broken and needs
      fixing. The cost of healthcare has outpaced every other sector of American life.
      We spend 2.5 times more on healthcare than do most developed countries in the
      world. Do we have the best healthcare in the world? The average life expectancy
      is 78.49 years, which ranks us 51st in the world. We spend more on healthcare
      than any other nation but get less for our hard-earned dollars. This article will
      provide suggestions for repairing the broken healthcare system with excerpts
      taken from the book Practical Wisdom, by Dr. Barry Schwartz and Kenneth Sharpe.

PMID- 26223109
TI  - Employment Agreements in the Healthcare Practice.
AB  - Employment agreements, written for partners, associates, and senior
      administrative staff members, provide clear guidance and establish a meeting of
      the minds on those critical issues for the efficient operation of a healthcare
      practice. This article outlines the rationale for the employment agreement and
      describes the basic issues to be considered and included in a good employment
      agreement.

PMID- 26223110
TI  - "Deer in the Headlights": Improving Patient Literacy.
AB  - As patients become more involved in their healthcare, the need for increased
      patient literacy becomes more evident. Unfortunately, too many patients are not
      able to understand their healthcare needs; this, in turn, affects compliance.
      Healthcare providers should strive to increase the patient's level of
      understanding of his or her own healthcare needs, because there is a direct
      correlation between understanding and compliance.

PMID- 26223111
TI  - The Value of an Elective in Business and Leadership for Medical Students.
AB  - This report describes the impact of the implementation of an elective in business
      and leadership targeted to preclinical medical students. Of the 42 students who
      completed the elective, 30 (71%) completed the survey. Students reported that
      they had a better understanding of the U.S. healthcare system (p <.01), had a
      better understanding of the role of physician-leaders (p <.01), and were more
      inclined to pursue managerial positions in medicine during their career (p <.01).
      We determined that an elective in business and leadership in medicine is a
      valuable addition to the standard undergraduate medical curriculum to enhance
      medical student exposure to the principles of the business of medicine and
      physician leadership.

PMID- 26223112
TI  - Ten Most Commonly Asked Questions About Collections in the Medical Practice.

PMID- 26223113
TI  - Waiving Deductibles and Copays: No Good Deed Goes Unpunished.
AB  - In an age of high deductibles, many surgical candidates are requesting that
      practices reduce or waive the self-pay portion of the professional fee. These
      requests come with a risk to the practice. Third-party payer agreements often
      prohibit discounting of fees to patients. Claiming breach of contract and
      interference with actuarial calculations, some third-party payers have sued
      practices for waiving fees owed by their insureds. Only by having the proper
      policies in place may a practice safely engage in fee reductions for patients
      insured by an entity with whom the practice has a contractual relationship.

PMID- 26223115
TI  - M-Health: Evolution or Revolution?

PMID- 26223114
TI  - Managing Your Team's Weakest Link.
AB  - Do you have a poor-performing employee on your medical practice team? If so,
      you're not alone. Unfortunately, this is a problem that many medical practice
      managers face. This article describes the best strategies for managing your
      team's weakest link. It explores common yet very difficult circumstances that
      cause low employee performance and that test the patience, heart, and skills of a
      practice manager. It guides readers through a process of self-discovery to
      determine whether their negative biases or grudges may be causing employees to
      perform poorly. It suggests several possible other reasons for weak employee
      performance, including problems with the job, practice, leadership,
      communication, and fit between the employee and the job. This article also
      suggests the best strategy for communicating concerns about performance to the
      weakest-link employee. It offers guidance to practice managers about protecting
      their time and energy when handling a poor performer. It provides a simple
      formula for calculating the cost of a low-performing employee, 10 possible
      personal reasons for the employee's poor work performance, specific questions to
      ask to uncover the reasons for poor performance, and an eight-rule strategy for
      confronting poor performance effectively. Finally, this article offers practice
      managers a practical strategy for handling resistance from their weakest link,
      illustrated with a sample dialogue.

PMID- 26223116
TI  - Patient Satisfaction: What We Can Learn from Other Industries.
AB  - Most doctors are appreciated by their patients, and most patients are satisfied
      with the care they receive from their doctors. However, how many doctors are
      reaching out and asking, as New York's former Mayor Koch often did, "Hey, how am
      I doing?" This article reviews two examples of effective methods used by other
      industries to gather data and evaluate customer satisfaction, and provides ideas
      and suggestions to measure patient satisfaction in a medical practice.

PMID- 26223117
TI  - [Role of Nrf2 in neurodegenerative diseases and recent progress of its
      activators].
AB  - The nuclear factor erythroid 2 related factor 2 (Nrf2) is a key protein of
      endogenous antioxidant defense systems in the body. In response to oxidative
      stress, Nrf2 translocates to nucleus and binds to antioxidant response elements
      (ARE), regulating the expression of a large amounts of antioxidant genes and
      maintaining a proper redox balance. The pathological processes of
      neurodegenerative diseases are associated with generation of reactive oxygen
      species, which cause oxidative stress. Oxidative stress plays a cardinal role in
      the onset and progression of neurodegenerative diseases. Nrf2-inducer compounds
      can reduce oxidant stress and have shown therapeutic efficacy in many
      neurodegenerative disease models. How to activate the Nrf2 signaling pathway
      effectively has been received much attention. Here we provided an overview of
      specific mechanism of Nrf2-ARE pathway and the protective effects of Nrf2 in
      different neurodegenerative diseases, and summarized the Nrf2 activators recently
      in preclinical study.

PMID- 26223118
TI  - [The TGF-beta signaling pathway induced EMT in breast cancer].
AB  - Epithelial-mesenchymal transition (EMT) refers to tne transition during which
      epithelial cells undergo the loss of apical-basal polarity, acquisition of
      migration capability and transformation into mesenchymal cells. EMT induces
      breast cancer in situ to developing into metastasis and associates with the drug
      resistence. The multiple elements including signal pathways, transcriptional
      factors and downstream genes orchestrate the transition. Among them, the
      transforming growth factor beta (TGF-beta) signaling pathway plays a key role in
      the regulation of EMT in breast cancer. And this paper reviews the development of
      TGF-beta signaling pathway induced EMT in breast cancer.

PMID- 26223119
TI  - [Research advances of M3 receptor: a new target for treating and preventing
      cardiovascular disease].
AB  - Cardiovascular disease, with high morbidity and mortality, has been threatening
      the health of human beings. Therefore, expecting to find a more effective
      therapeutic method, a plenty of researchers devote themselves to the study of the
      cardiovascular disease all the time. Since discovered on the heart, M3 receptor
      of muscarinic acetylcholine receptor (mAchR, M receptor) became a new starting
      point of the research of the cardiovascular disease. With more and more
      investigation, many people found that M3 receptor could protect the heart from
      kinds of cardiovascular disease, which may make it a new hopeful therapeutic
      point. So, expecting to give support to the reference and encouragement for the
      study of disease related to M3 receptor in future, this review expounds M3
      receptor on the heart from the main following aspects: the effect on the heart,
      the influence on the cardiovascular disease and the mechanism of M3 receptor
      involved.

PMID- 26223120
TI  - [Regulation of organic anion transporting polypeptides expression and activity].
AB  - Organic anion transporting polypeptides (OATP), a member of solute carrier (SLC)
      superfamily, is considered as an important transmembrane uptake transporters.
      OATP is involved in the transport of a variety of endo- and xenobiotics (bile
      acids, bilirubin, prostaglandin, thyroid hormones, steroid hormone conjugates),
      drugs and toxins in a Na+ and ATP independent manner. Multiple factors (eg.
      hormones, proinflammatory cytokines, drugs) can affect the distribution,
      expression and activity of OATPs, leading to an altered accumulation of OATP
      substrates and related food-drug and drug-drug interactions. Changes in the
      distribution and expression of OATPs in malignant tissues may be related to the
      pathological process of cancer, while the modulation epigenetic mechanism also
      contributes to its distribution patterns. This review describes the factors that
      can affect the expression or function of OATPs, which may provide a valuable
      reference for drug development and the clarification of pathogenesis.

PMID- 26223122
TI  - [Advances of transforming growth factor-beta inhibitors].
AB  - Transforming growth factor-beta is an important cytokine with various
      bioactivities, including embryonic development, wound healing, chemotaxis and
      cell cycle regulation. Epithelial-mesenchymal transition (EMT) is the main
      pathway of tumor cell to obtain the ability of invasion and metastasis. The TGF
      beta is the key factor known to induce EMT in cancer cells and plays an important
      role in the process. In recent years, some progress has been obtained. Some TGF
      beta inhibitors have approved in the market or in clinical trials. TGF-beta
      inhibitors can play an important role on the treatment of tumors, glaucoma, liver
      and kidney fibrosis disease and scar repair. Novel TGF-beta inhibitors reported
      in recent years were reviewed in this article.

PMID- 26223121
TI  - [Advances in the study of enzymes and transporters-mediated pharmacokinetic
      mechanism for herb-drug interaction].
AB  - With the wide application of Chinese herbal medicine, herb-drug interaction (HDI)
      has become increasingly prominent. Metabolic enzymes and transporters are the
      main targets of HDI, because the changes in expression and function of enzymes
      and transporters can influence the disposition of drugs. Metabolic enzymes are
      responsible for the metabolic clearance of drugs, including cytochrome P450
      (CYP), UDP-glucuronyl transferase (UGT) and sulfotransferases (SULT);
      transporters widely expressed in the intestine, kidney, liver and brain are
      involved in the oral absorption, distribution and excretion of drugs. Pueraria,
      ginkgo, ginseng, St. John's wort and other Chinese herbal medicine often induce a
      HDI because those herbal medicines combined with chemical medicine are widely
      used in clinic. The components of herb medicines mentioned above are prone to
      interact with enzymes and transporters, which often induce a HDI. This paper
      reviews the advances in the study of enzymes and transporters-mediated
      pharmacokinetic mechanism of HDI.

PMID- 26223123
TI  - [Diversity-oriented synthesis and its application in drug discovery].
AB  - Diversity-oriented synthesis (DOS) aims to efficiently generate collections of
      small molecules with diverse appendages, functional groups, stereochemistry and
      skeletons, thus yielding diverse biological activities capable of modulating a
      wide variety of biological processes. In this review, we discussed the common
      strategies employed in DOS with specific examples from recent literature,
      including reagent-based approach, substrate-based approach, build-couple-pair
      strategy and privileged substructure-based DOS. The application of some DOS
      libraries in drug discovery is also presented.

PMID- 26223124
TI  - [Poly(beta-amino esters)-based barriers for tumor targeted delivery system].
AB  - Poly(beta-amino esters) (PBAE) are used for drug carrier and have many
      advantages, such as pH-sensitivity, low toxicity, structural diversity and the
      synthetic method of PBAE is easy. Therefore they are possessed broad application
      prospect in tumor-targeted drugs delivery systems. In this paper, the structural
      features and target drugs delivery property of PBAE are reviewed. The application
      forms of PBAE and different anti-cancer drugs loaded in the copolymer for tumor
      targeted drugs delivery systems are introduced particularly.

PMID- 26223125
TI  - [The in vitro anti-atherosclerotic activity of compound E0869].
AB  - ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I
      (SR-BI/CLA-1) are the key proteins in reverse cholesterol transport (RCT). The
      high expression of ABCA1 and SR-BI/CLA-1 can decrease the danger of
      atherosclerosis. The purpose of the study is to find ABCA1 and CLA-1up-regulators
      for treating atherosclerosis by using cell-based high throughput screening
      models. Among 20 000 compounds screened, E0869 [1-(3, 4-dimethylphenyl)-1
      oxopropan-2-yll4-((methylsulfonyl)methyl)benzoate] was found as the positive hit.
      The up-regulated activities of E0869 in ABCAl1-LUC and bCA-l1-LUC HepG2 cell were
      160% and 175%, respectively. The EC50 values of E0869 in ABCAl1-LUC and CLA-l1
      LUC HepG2 cell were 3.79 and 1.42 pMUol- x ,(-1) respectively. E0869 could
      upregulate the mRNA and protein levels of ABCA1, SR-BI/CLA-1 and ABCGJ1genes in
      HepG2 and RAW264.7 cells by Real-Time Quantitative PCR and Western blotting
      analysis, but could not influence the expression of FAS, SREBP-l1 and CD36. Foam
      cell assay showed that E0869 could inhibit lipids accumulation in mouse
      peritoneal macrophages RAW264.7. Cholesterol efflux assay showed that E0869 could
      induce HDL-mediated cholesterol efflux in mouse peritoneal macrophages RAW264.7.
      In conclusion, E0869 could up-regulate ABCA1 and CLA-1 activity, and had good
      anti-atherosclerotic activity in vitro.

PMID- 26223126
TI  - [Establishment of double targets of high throughput screening model for xanthine
      oxidase inhibitors and superoxide anion scavengers].
AB  - A double targets of high throughput screening model for xanthine oxidase
      inhibitors and superoxide anion scavengers was established. In the reaction
      system of xanthine oxidase, WST-1 works as the probe for the ultra oxygen anion
      generation, and product uric acid works as xanthine oxidase activity indicator.
      By using SpectraMax M5 continuous spectrum enzyme sign reflectoscope reflector,
      the changes of these indicators' concentration were observed and the influence
      factors of this reaction system to establish the high throughput screening model
      were studied. And the model is confirmed by positive drugs. In the reaction
      system, the final volume of reaction system is 50 MUL and the concentrations of
      xanthine oxidase is 4 mU x mL(-1), xanthine 250 MUmol x L(-1) and WST-1 100 MUmol
      x L(-1), separately. The Z'-factor of model for xanthine oxidase inhibitors is
      0.537 4, S/N is 47.519 9; the Z'-factor of model for superoxide anion scavengers
      is 0.507 4, S/N is 5.388 9. This model for xanthine oxidase inhibitors and
      superoxide anion scavengers has more common characteristics of the good
      stability, the fewer reagent types and quantity, the good repeatability, and so
      on. And it can be widely applied in high-throughput screening research.

PMID- 26223127
TI  - [Therapeutic effects and mechanisms of Opuntia dillenii Haw on atherosclerosis of
      rats].
AB  - The research aimed to investigate the therapeutic effects and mechanisms of
      Opuntia dillenii Haw polysaccharide (OPS) on atherosclerosis of rats. First
      atherosclerotic rat models were established by high-fat and high-calcium diet.
      Thirty days later, the rats were treated with low dosage of OPS (0.2 g x kg(-1) x
      d(-1)) or high dosage of OPS (0.4 g x kg(-1) x d(-1)) by intraperitoneal
      injection for 60 days continuously. At the end of treatment, thoracic aorta rings
      were prepared and vasorelaxation of rat thoracic aorta in different experiment
      groups were determined by using 620M multi wire myograph system in vitro. Blood
      and livers of rats were collected. Then plasma levels of total cholesterol (TC),
      triglyceride (TG) and low density lipoprotein (LDL) of rats were separately
      determined using whole automatic biochemical analyzer; protein level of hepatic
      apolipoprotein B (ApoB) and that of hepatic diglyceride acyltransferase (Dgat1)
      were measured by Western Blot technique. Results showed that the ability of rat
      thoracic aorta to relax decreased markedly in the model group compared with that
      in the normal group, and significant differences existed in vasorelaxation ratios
      induced by different concentrations of carbamylcholine chloride (Carb) between
      these two groups (P < 0.01). After OPS treatment, the ability of rat thoracic
      aorta to relax improved markedly, the vasorelaxation ratios induced by Carb at 5
      and 10 MUmol x L(-1) were respectively 0.34 +/- 0.08 and 0.62 +/- 0.15 in the
      group treated with low dosage of OPS, while the ratios induced by Carb at 1 and 5
      MUmol x L(-1) were respectively 0.54 +/- 0.08 and 0.98 +/- 0.02 in the group
      treated with high dosage of OPS, which were all significantly different with
      those in the model group (P < 0.01). Plasma contents of TC, TG and LDL reduced
      significantly by the treatments both with low and high dosages of OPS compared
      with those in the model group (P < 0.01). Protein level of hepatic ApoB and that
      of hepatic Dgat1 decreased significantly after the treatment with high dosage of
      OPS compared with those in the model group (P < 0.01). These results indicate
      that OPS can markedly improve the vasorelaxation of thoracic aorta of
      atherosclerotic rats and has significant anti-atherosclerotic effect; inhibiting
      the expression of ApoB and Dgat1 and thus decreasing the amounts of TC, LDL and
      TG serving as one of the molecular mechanisms of its antiatherosclerosis effect.

PMID- 26223128
TI  - [Borneol is an inducer of rat hepatic CYP2D activity in vivo].
AB  - Borneol is a traditional Chinese medicine. In the past few years, many studies
      showed that borneol can improve the bioavailability of other drugs, promoting
      drugs to cross the blood-brain barrier, so the potential drug interactions
      between borneol and other medicines have attracted great attention, but the
      influence of borneol to CYP450 and its isoforms are rarely reported. In this
      research, male Wistar rats were orally administered by borneol for 7 days, then
      the mRNA and protein expression and the activities of CYP2D were detected, we
      also compared the pharmacokinetic parameters of CYP2D's specific substrate
      between control group and borneol group. The results show that borneol (33, 100
      and 300 mg x kg(-1) x d(-1)) have no significant effect on CYP2D, while the
      activites of CYP2D increased 1.71, 1.97 and 2.89 times comparing to the control
      group. At the same time, borneol (300 mg x kg(-1) x d(-1)) caused the C(max)
      decreased 10.6% (P > 0.05), AUC(0-infinity) decreased 27.5% (P < 0.01), CL/F
      increased 41.1% (P < 0.01), V(z)/F increased 23.1% (P > 0.05) of
      dextromethorphan. Our data provided that borneol speed up dextromethorphan's
      elimination in vivo. Since the activity of CYP2D can be induced by borneol, the
      metabolic interactions might happen when borneol and the substrate drug CYP2D are
      used together.

PMID- 26223129
TI  - [Design, synthesis and antitumor activities of novel E-substituted 2,3-diaryl
      propenoic acyloxy phosphonate derivatives].
AB  - According to the super-position principle of the reinforcement of biological
      activities, a series of novel E-substituted 2, 3-diaryl propenoic acyloxy
      phosphonate derivatives were designed and synthesized. And the structures of the
      target compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis.
      Furthermore, the cytotoxicities of all compounds on A-549, SGC-7901 and EC-109 in
      vitro were evaluated by MTT assay, and some of them showed good antitumor
      activity. Among the active compounds, especially, the IC50 value of compound 3e
      was (12.7 +/- 1.9) MUmol x L(-1) against A-549 cells, similar to cisplatin [IC50
      = (8.0 +/- 1.5) MUmol x L(-1)], compounds 3g and 3k had better inhibition effect
      on EC-109 cells growth, with the IC50 values of (9.5 +/- 1.8) MUmol x L(-1) and
      (11.5 +/- 0.9) MUmol x L(-1) respectively, and compounds 3i and 3k exhibited good
      cytotoxic property on A-549, SGC-7901 and EC-109, which were worth further
      investigation.

PMID- 26223130
TI  - [Synthesis and anti-tumor activity of oleanolic acid derivatives].
AB  - Thirteen novel oleanolic acid (OA) derivatives were designed and synthesized with
      modification at positions of C-3, C-12 and C-28 of OA. Their structures were
      confirmed by MS, 1H NMR and elemental analysis. Their in vitro cytotoxicities
      against various cancer cell lines (SGC7901, MCF-7 and A549) were evaluated by MTT
      assay. The results indicated that the tested derivatives were found to have
      stronger cell growth inhibitory activity than OA. Among them, compounds II2 and
      II3 showed more potent cytotoxicity on MCF-7 and A549 tumor cells than gefitinib
      (positive control). They are worthy to be studied further.

PMID- 26223131
TI  - Chemical constituents from stems and leaves of Micromelum integerrimum.
AB  - A new benzene derivative microintegerrin C (1) and a new norsesquiterpenoid
      microintegerrin D (2), along with six known compounds (3-8), were isolated and
      identified from stems and leaves of Micromelum integerrimum by various
      chromatographies such as silica gel, Sephadex LH-20, RP-18 column chromatography
      and HPLC. Their structures were mainly identified based on the spectral data
      analysis such as 1D-, 2D-NMR and HR-EI-MS. All known compounds were isolated from
      this plant for the first time.

PMID- 26223132
TI  - [Quantitative analysis of seven phenolic acids in eight Yinqiao Jiedu serial
      preparations by quantitative analysis of multi-components with single-marker].
AB  - The study aims to develop a unified method to determine seven phenolic acids
      (neochlorogenic acid, chlorogenic acid, 4-caffeoylquinic acid, caffeic acid,
      isochlorogenic acid B, isochlorogenic acid A and isochlorogenic acid C) contained
      in honeysuckle flower that is the monarch drug of all the eight Yinqiao Jiedu
      serial preparations using quantitative analysis of multi-components by single
      marker (QAMS). Firstly, chlorogenic acid was used as a reference to get the
      average relative correction factors (RCFs) of the other phenolic acids in ratios
      to the reference; columns and instruments from different companies were used to
      validate the durability of the achieved RCFs in different levels of standard
      solutions; and honeysuckle flower extract was used as the reference substance to
      fix the positions of chromatographic peaks. Secondly, the contents of seven
      phenolic acids in eight different Yinqiao Jiedu serial preparations samples were
      calculated based on the RCFs durability. Finally, the quantitative results were
      compared between QAMS and the external standard (ES) method. The results have
      showed that the durability of the achieved RCFs is good (RSD during 0.80% -
      2.56%), and there are no differences between the quantitative results of QAMS and
      ES (the relative average deviation < 0.93%). So it can be successfully used to
      the quantitative control of honeysuckle flower principally prescribed in Yinqiao
      Jiedu serial preparations.

PMID- 26223134
TI  - [Preparation and release behaviour of mesoporous silica/ethylcellulose sustained
      release mini-matrix].
AB  - Hot-melt extrusion was applied to prepare mesoporous silica/ethylcellulose mini
      matrix for sustained release, and fenofibrate was used as a model drug,
      ethylcellulose and xanthan gum were chosen as sustained-release agent and
      releasing moderator, respectively. This novel matrix obtained the controlled
      release ability by combining mesoporous silica drug delivery system and hot-melt
      extrusion technology. And mesoporous silica particle (SBA-15) was chosen as drug
      carrier to increase the dissolution rate of fenofibrate in this martix. Scanning
      electron microscope, transmission electron microscope, small angle X-ray powder
      diffraction and N2 adsorption-desorption were introduced to determine the
      particle morphology, particle size and pore structure of the synthesized SBA-15.
      The results showed that SBA-15 had a very high Brunauer-Emmett-Teller specific
      surface area, a narrow pore size distribution, large pore volume and a ordered
      two-dimensional hexagonal structure of p6mm symmetry. Differential scanning
      calorimetry and X-ray powder diffraction results demonstrated that fenofibrate
      dispersed in an amorphous state inside the pores of the mesoporous silica which
      contributed to the improvement in the dissolution rate. The drug release of mini
      matrices was influenced by ethylcellulose viscosity grades and xanthan gum
      concentration, which increased with the increasing of xanthan gum concentration
      and decreasing of ethylcellulose viscosity. Mini-matrix containing 22% xanthan
      gum exhibited a good sustained release performance, and the drug release behavior
      followed the first-order kinetics.

PMID- 26223133
TI  - [The enantioselective pharmacokinetic study of desvenlafaxine sustained release
      tablet in Chinese healthy male volunteers after oral administration].
AB  - A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS)
      enantiomers in human plasma was developed and applied to a pharmacokinetic study
      on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard
      (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral
      column (150 mm x 4.6 mm, 5 MUm). The assay was linear over the concentration
      range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was
      successfully applied to a stereoselective pharmacokinetic study of 100 mg
      desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under
      fasting conditions. The results showed that the pharmacokinetic parameters were
      similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and
      C(max) of the two enantiomers were about 1.5 times higher than those of blacks
      and whites reported in the literature.

PMID- 26223135
TI  - [Development of microsatellites and genetic diversity analysis of Scutellaria
      baicalensis Georgi using genomic-SSR markers].
AB  - A total of 12 775 SSRs were identified from Scutellaria baicalensis Georgi
      genomic database, accounting for 2.56% of the total genomic sequences. The result
      showed that S. baicalensis SSRs were based on 68.32% dinucleotide and 18.63%
      trinucleotide repeats; CT/GA and TTC/GAA were predominant in the dinucleotide
      motifs and the trinucleotide motifs respectively. Nine primers were selected to
      produce highly reproducible SSR bands and were used in studying the genetic
      diversity of S. baicalensis, 50 individuals from ten populations. 68 SSR
      polymorphic loci were detected, these loci were polymorphic and displayed 4 to 12
      alleles per locus with a mean number of 7; the effect number of alleles was 3.
      Expected heterozygosities were 0.6 and were far more greater than the average in
      dicotyledonous plants. PIC (polymorphism information content) was 0.72, Shannon's
      information index was 1.32, these all proved that S. baicalensis had a high
      genetic diversity in general. Genetic differentiation among population Gst was
      0.131, genetic variation among population accounted for 13.1% and genetic
      variation within population accounted for 86.9%. The cluster analysis showed that
      10 populations S. Baicalensis were classified into 2 groups, but it was not
      associated with geographical distribution.

PMID- 26223136
TI  - An appraisal of convergence failures in the application of logistic regression
      model in published manuscripts.
AB  - BACKGROUND: Logistic regression model is widely used in health research for
      description and predictive purposes. Unfortunately, most researchers are
      sometimes not aware that the underlying principles of the techniques have failed
      when the algorithm for maximum likelihood does not converge. Young researchers
      particularly postgraduate students may not know why separation problem whether
      quasi or complete occurs, how to identify it and how to fix it. OBJECTIVE: This
      study was designed to critically evaluate convergence issues in articles that
      employed logistic regression analysis published in an African Journal of Medicine
      and medical sciences between 2004 and 2013. METHODS: Problems of quasi or
      complete separation were described and were illustrated with the National
      Demographic and Health Survey dataset. A critical evaluation of articles that
      employed logistic regression was conducted. RESULTS: A total of 581 articles was
      reviewed, of which 40 (6.9%) used binary logistic regression. Twenty-four (60.0%)
      stated the use of logistic regression model in the methodology while none of the
      articles assessed model fit. Only 3 (12.5%) properly described the procedures. Of
      the 40 that used the logistic regression model, the problem of convergence
      occurred in 6 (15.0%) of the articles. CONCLUSION: Logistic regression tends to
      be poorly reported in studies published between 2004 and 2013. Our findings
      showed that the procedure may not be well understood by researchers since very
      few described the process in their reports and may be totally unaware of the
      problem of convergence or how to deal with it.

PMID- 26223137
TI  - The influence of sex hormone levels on tear production in postmenopausal Nigerian
      women.
AB  - BACKGROUND: A stable tear film with normal flow is essential for preserving a
      clear cornea. When the tear film becomes insufficient to support the surface of
      the eye due to a lack of production of tears or a decrease in stability of tears,
      dry eye syndrome (DES) occurs. DES is a common disorder of the tear film. It
      affects a significant percentage of the population, especially women. The onset
      of dry eye is very common during menopause and may result from the loss of
      hormonal support. OBJECTIVE: The purpose of this study was to assess the effect
      of sex hormone on tear volume and stability in postmenopausal Nigerian women.
      METHOD: This study was a cross sectional experimental study. Twenty
      postmenopausal women aged 50 to 55 years (mean age 52 +/- 2.32) and twenty
      premenopausal women aged 45 to 52 years (mean age 50 +/- 2.13) were selected by
      systematic random sampling. Schirmer's tear test and the noninvasive tear break
      up time (NITBUT) test were performed on the women. Serum levels of estradiol,
      progesterone and testosterone were determined. RESULTS: The differences in mean
      tear volume, (t = 14.74, p < 0.0001) and tear stability, (t = 11.28, p < 0.04)
      between the postmenopausal and premenopausal women were statistically
      significant. Tear volume was positively correlated with testosterone (r = 0.276,
      p >= 0.05) and progesterone (r = 0.227, p >= 0.05) but negatively correlated with
      estradiol (r = 0.141, p >= 0.05) in the postmenopausal group, with no
      statistically significant associations. CONCLUSION: Changes in hormone levels
      that occur in menopause affect tear volume and tear stability.

PMID- 26223138
TI  - Neurobehavioural activities of the ethanol leaf extract of calophyllum inophyllum
      in rodents.
AB  - AIM: The present study was designed to investigate the central nervous system
      activities of the ethanol leaf extract of Calophyllum inophyllum in rodents.
      METHODS: The neurobehavioural tests used include the hole board, open field,
      elevated plus maze and the light/dark box tests. The animals were divided into
      the control (normal saline, 10 ml/kg) experimental (50-150 mg/kg) and the
      reference groups (indomethacin,10 mg/kg) after which they were subjected to the
      above tests. RESULTS: The results showed that in the hole board test, the 100 and
      200 mg/kg doses resulted in a significant (p < 0.01) reduction in the number of
      head dips compared with the control, while in the light and dark box test there
      was a significant (p < 0.01) increase in the time spent in the dark arena
      compared with the control. The open field test revealed a reduction in the total
      locomotion compared with the control although not statistically significant,
      While the time spent in the closed arm increased significantly (p < 0.05) at all
      doses, the rearing frequencies were significantly (p < 0.05) reduced at all
      doses, only the 200 mg/kg dose reduced the grooming frequencies significantly (p
      < 0.05). CONCLUSION: These results suggest that the ethanol leaf extract of
      Calophyllum inophyllum contains some active principles which may be
      sedative/anxiogenic in nature.

PMID- 26223139
TI  - Regional anaesthetic technique for laparoscopic appendicectomy in Ibadan.
AB  - BACKGROUND: Laparoscopy is now readily being deployed for abdominal surgeries in
      our centre, thanks to the surgeons' interest and the desire to follow best
      practice as obtained in other climes. General anaesthesia (GA) with intermittent
      positive pressure ventilation is usually the preferred mode of anaesthesia for
      this procedure. There are reports of laparoscopic surgery of abdomen performed
      under spinal and or epidural anaesthetic techniques. METHODS: With Intra
      Abdominal Pressure (IAP) from CO2 insufflations limited to 10-12 mmHg,
      Laparoscopic Appendicectomy (LA) was performed under Combined Spinal Epidural
      (CSE) for ten consenting ASA 1 and II patients with mean age 23.6 years and BMI
      of 24.9 kg/m2 in University College Hospital Ibadan, Nigeria. Intra-operative
      events and ease of operation were studied; systemic drugs were administered if
      patients complained of pain and discomfort, and G.A if regional techniques and
      sedation failed. RESULTS: Eight(8) patients had the procedure completed under
      spinal anaesthesia supplemented with sedation, two (2) patients whose block went
      as high as T4 had no need of sedation. There were operative difficulties in four
      patients out of which 2 had sedations and the surgeons could continue operating.
      We converted to GA in two (2) patients when regional techniques and sedation
      failed. CONCLUSION: We concluded that with proper selection of patients and
      limiting IAP to 10-12 mmHg, LA can be safely performed with spinal anaesthesia
      with some supplementation.

PMID- 26223140
TI  - The wits appraisal using three reference planes and its interaction with the ANB
      angle among a sub-set of Nigerians".
AB  - AIMS: Conjoint analysis of orthodontic patients using the Subspinale (A-point)
      Nasion-Supramentale (B point) (ANB) angle and the Wits appraisal is popular in
      many practices. This study aimed to present reference values for the Wits
      appraisal among Nigerians using three horizontal reference planes namely the
      bisected occlusal plane (BOP), the functional occlusal plane (FOP) and the
      maxillomandibular angle bisector (MM degrees  bisector) plane. It also assessed
      the relationship of the Wits appraisal with the ANB angle and its interaction
      with clinical measures of sagittal skeletal relations among subjects with
      malocclusion. METHODOLOGY: One hundred participants with normal occlusion and 120
      with malocclusion were recruited in the study. Cephalometric radiographs were
      taken for all participants. Each radiograph was manually traced on a 0.003 matted
      cellulose acetate tracing paper using a sharpened 2H pencil. The Wits appraisal
      and ANB angle were determined. Data was analyzed using SPSS version 19. RESULTS:
      The mean age was 20.7 +/- 4.9 years for those with normal occlusion and 18.8 +/-
      6.5 years in the malocclusion group. There were 91 (41.4%) males and 129 (58.6%)
      females. Mean values for the Wits appraisal using the BOP as reference, was--1.27
      +/- 2.91mm, with the FOP, it was -3.54 +/- 3.24mm, while with the MM degrees 
      bisector plane, it was--.75? +/- .94mm. The ANB angle showed highest correlation
      with the MM' degrees bisector plane Wits value(P< 0 .001). CCONCLUSION: hen the
      clinical and angular cephalometric findings are at variance, the ANB angle is
      best moderated by the MM' degrees  isector plane Wits appraisal.

PMID- 26223141
TI  - Sanitary conditions of abattoirs in Ibadan, Southwest Nigeria.
AB  - BACKGROUND: The environment in the abattoir is of public health concern because
      of its implications on the quality of meat sold in the markets. The poor sanitary
      states of abattoirs have been reported in the literature. Very few studies have
      provided a comprehensive assessment of the sanitary conditions in the abattoir
      premises. This study sought to assess the compliance of abattoirs in Ibadan,
      Southwest Nigeria with standards set by Federal Ministry of Environment.
      METHODOLOGY: A descriptive cross-sectional study was conducted in Ibadan using an
      observational checklist adapted from Policy guidelines on market and abattoir
      sanitation by the Federal Ministry of Environment. Twelve (12) abattoirs in
      Ibadan metropolis were assessed. Data obtained were analyzed using descriptive
      statistics. RESULTS: Concerning general inspection, only one (8.3%) of the
      abattoirs had adequate access route, potable water supply and functional drainage
      system. Many had poor solid waste management practices as heaps of refuse
      littered the surroundings. Internal inspection of the abattoirs revealed that two
      (16.7%) had adequate space and facilities. Ten (83.3%) had first aid posts even
      though they were not equipped with materials. Eleven (91.7%) abattoirs had toilet
      facilities that were either poorly kept or abandoned. CONCLUSION: This study
      showed that most of the abattoirs in Ibadan metropolis were operating under
      unhygienic and sub-standard conditions and lacked basic requirements for a good
      abattoir as stipulated in the Policy Guidelines on Market and Abattoir
      Sanitation. There is an urgent need to enforce the minimum standards as
      stipulated in the policy guidelines.

PMID- 26223142
TI  - Prevalence and pattern of early childhood caries in Ibadan, Nigeria.
AB  - BACKGROUND: Early childhood caries is a public health problem in a developing
      country such as Nigeria where there are limited resources to combat the
      situation. AIM: The aim of the study is to determine the prevalence and pattern
      of early childhood caries (ECC) among nursery school children aged 3 to 5 years
      in Ibadan, Nigeria. METHODS: A cross sectional study was conducted on 540 nursery
      school children aged 3 to 5 years old in nursery schools within Ibadan. Oral
      examination was performed and dmft (decayed-missing-filled teeth) indices were
      recorded. Data was analyzed using SPSS 16.0 and descriptive statistics was
      applied. The level of significance was taken at p value < 0.05. RESULTS: The
      prevalence of early childhood caries was 23.5% with a total of 353 carious teeth
      seen in 127 children. The mean dmft was 0.65 +/- 1.49 and the decayed (d)
      component constituted 100% of the dmft scores (all dmft was due to untreated
      caries). The second mandibular primary molars were the teeth most affected by
      caries, accounting for 35.4% of all decayed teeth. Severe ECC prevalence was
      2.2%. CONCLUSION: The high caries prevalence observed on the second mandibular
      primary molars reveals the rampant nature of this disease and the absence of any
      missing or filled tooth in the dmft indices shows poor dental awareness among the
      parents/guardians of the children.

PMID- 26223143
TI  - Computed tomography measurement of extra-ocular muscle diameters in a population
      of normal patients in a tertiary hospital in Nigeria.
AB  - BACKGROUND: Measurements of extraocular muscle diameter may be useful in
      diagnosis and as an outcome indicator in the assessment of treatment options in
      thyroid-associated ophthalmopathy. Racial differences are known to account for
      craniofacial variations and orbital sizes. OBJECTIVE: To determine the normal
      diameters of extra-ocular muscles using computed tomography in a homogeneous,
      group of hospital patients in a tertiary hospital in Nigeria. MATERIAL AND
      METHOD: The maximum diameters of extra-ocular muscles were measured for 182
      normal patients on thin slice reconstructed coronal computed tomography images.
      The effects of age and sex were determined. RESULT: Normal ranges for the
      diameters (mean + 2 SDs) of extraocular muscles were 4.5 + 1.2 mm for medial
      rectus, 4.9 + 2.1 mm for lateral rectus, 4.8 + 1.6 mm for inferior rectus and 4.0
      + 1.5 mm for the superior group. The mean diameter of the extra-ocular muscles of
      male patients was not significantly larger than that of female patients (p >
      0.05). There was a small but positive correlation between age and diameter of
      each extra-ocular muscle except in the left medial rectus and right lateral
      rectus muscles (P < 0.05). CONCLUSION: These normative values may serve as
      radiological reference values in the assessment of changes in size and suspected
      enlargement of the extraocular muscles in Nigerian patients. They may also be
      extrapolated to other Black African patients, until population studies become
      available.

PMID- 26223144
TI  - Assessment of nurses' knowledge on evidence-based preventive practices for
      pressure ulcer risk reduction in patients with impaired mobility.
AB  - BACKGROUND: The increase in the prevalence of pressure ulcer among patients with
      impaired physical mobility has currently been associated with nurses' inadequate
      knowledge of preventive interventions. AIM: To assess nurses' knowledge of
      pressure ulcer identification/staging, risk factors and evidence-based preventive
      practices. METHOD: This descriptive study was carried out at the University
      Teaching Hospital Maiduguri (UMTH), Borno State, Nigeria. Total sampling
      technique was utilized in the recruitment of the study participants. An adapted
      75-item-pressure ulcer questionnaire was used for data collection. The data were
      analyzed using SPSS version 16. The hypotheses on nurses' knowledge were tested
      at 0.05 level of significance using Chi square test. RESULTS: A total of 219
      nurses participated in this study with response rate of 68.0%. The nurses' years
      of professional practice ranged from 1 to 35 years with a mean of 11.7 (+/- 7.8)
      years. Approximately, 73% of the nurses demonstrated a low level of knowledge of
      pressure ulcer identification/staging, 69.4% demonstrated an average level of
      knowledge of risk factors and 79.9% demonstrated high level of knowledge of
      preventive practices. The relationship between nurses' knowledge of risk factors
      and knowledge of preventive practices (p = 0.37) was not significant. CONCLUSION:
      Nurses demonstrated a knowledge deficit in core areas on pressure ulcer
      identification/staging, risk factors' assessment and evidence-based preventive
      practices. In order to address this dearth, there is a need to institute an
      educational-based practice-guideline on pressure ulcer prevention for nurses.

PMID- 26223145
TI  - Serum copeptin and its diagnostic performance in schizophrenia.
AB  - BACKGROUND: Inappropriate arginine vasopressin (AVP) secretion has been reported
      in schizophrenic patients. However, there is lack of information on serum level
      of copeptin and its diagnostic performance in schizophrenia. This study
      therefore, evaluated serum copeptin and its diagnostic performance in
      schizophrenic patients. METHODS: Sixty subjects (30.02 +/- 7.17 years) with
      schizophrenia (19 drug naive [DNS] and 41 schizophrenics on treatment [SOT]) and
      30 healthy individuals (33.62 +/- 9.05 years) with no history of schizophrenia
      were enrolled into this study. Schizophrenia was diagnosed using the Tenth
      edition of the International Classification of Diseases and Related Health
      Problems (ICD-10). Estimation of serum copeptin, plasma electrolytes (potassium,
      sodium and chloride) and uric acid was done using ELISA, Ion-Selective electrode
      (ISE) and enzymatic method respectively. RESULTS: Copeptin was significantly
      higher while uric acid, potassium and sodium levels were significantly lower in
      patients with schizophrenia compared with controls. Similarly, copeptin was
      significantly higher while sodium, potassium and uric acid levels were
      significantly lower in DNS and SOT compared with controls. However, insignificant
      elevation in copeptin level and insignificant reduction in sodium, potassium,
      chloride and uric acid levels were observed in DNS compared with SOT. The Area
      under the curve (AUROC) for copeptin was 0.686 (P = 0.004). CONCLUSION: There is
      elevated copeptin level in patients with schizophrenia and that copeptin levels
      might be a valuable tool in the diagnosis of schizophrenia.

PMID- 26223146
TI  - Preliminary study of the baseline characteristics of patients, etiological agents
      of community-acquired pneumonia and mortality in Ibadan, Nigeria.
AB  - BACKGROUND: Studies relating the baseline characteristics of patients with
      community-acquired pneumonia and the bacterial etiological agents to the
      mortality of the disease are scanty in our environment. This study therefore
      aimed at determining the contribution of the baseline characteristics of patients
      with community-acquired pneumonia, the bacterial etiological agents to the
      mortality in our environment. METHODS: Data of patients with community-acquired
      pneumonia were retrieved and the effects of these on mortality were studied
      retrospectively. These data included age, gender, occupations, marital status,
      smoking, severity assessment using CURB 65 score, alcohol use, sources of
      referral, and bacterial etiological agents. These were subjected to statistical
      analysis using the SPSS version 15. RESULTS: The age groups with the highest
      mortality frequencies were those below 30 years (41.1%) and above 60 years
      (29.4%). Marital status, gender of patients, use of alcohol and smoking did not
      seem to affect the mortality rates. Eight patients had concomitant chronic
      obstructive pulmonary disease and four died (50.0%) while 12 patients had
      bronchial asthma, none of whom died. Patients with Pseudomonas aeruginosa
      infections had the highest mortality rates (5.9% and 17.6%) in cases of single
      and multiple pathogens respectively. None of the patients had severity score
      documented on admission. CONCLUSION: This is a preliminary study and further
      studies are necessary to determine the relationship of smoking, alcohol and
      etiological agents to mortality in community-acquired pneumonia using a larger
      population as study size.

PMID- 26223147
TI  - Plasma D-dimer reference ranges in pregnant Nigerians.
AB  - BACKGROUND: The use of D-dimer as a screening test for thromboembolic disorders
      has not been validated in pregnancy thus necessitating further studies. This
      cross sectional study was carried out among Pregnant Nigerians at the Nigerian
      Air Force Hospital Antenatal Clinic, Ikeja, Lagos. OBJECTIVE: This study was to
      determine local reference ranges for plasma D-dimer in both pregnant and non
      pregnant females and compare differences in both populations. METHODS: Structured
      questionnaires were administered on a total of 365 participants which included 71
      apparently healthy non-pregnant females, 64 women in the first trimester of
      pregnancy (<=13 weeks gestation); 65 women at the second trimester of pregnancy
      (14-26 weeks), and 82 pregnant females at the third trimester of pregnancy (> =
      27 weeks). Citrated blood was collected for estimation of prothrombin time (PT),
      activated partial thromboplastin time (aPTT), and D-dimer estimation by ELISA
      method. Aspartate aminotransferase (AST) and alanine aminotransferase enzymes
      (ALT) were estimated using the Hitachi chemistry analyzer. Reference ranges were
      estimated non-parametrically using the Reference Value Advisor V 2.1. RESULTS:
      Median D-dimer level for non-pregnant females was 190 ng/mL, while the median D
      dimer levels for pregnant female in 1st, 2nd, and 3rd trimester were 485 ng/ml;
      620 ng/mL; and 1185 ng/mL respectively.Reference ranges were calculated to be 86
      494 ng/mL; 338-624 ng/mL; 451-799 ng/mL and 665-1262 ng/mL for non-pregnant
      females, 1st, 2nd, and 3rd trimester of pregnancy respectively. CONCLUSION: A
      diagnostic algorithm for venous thromboembolism (VTE) in pregnant women which
      combines clinical suspicion with elevated plasma D-dimers levels above estimated
      reference range for each trimester should precede definitive formal imaging.

PMID- 26223148
TI  - Motor function and behaviour across the ALS-FTD spectrum.
AB  - BACKGROUND: Behavioural/functional disturbances, characteristic of frontotemporal
      dementia (FTD), are also a feature of amyotrophic lateral sclerosis (ALS) and
      patients with combined ALS and FTD (FTD-ALS). AIM OF THE STUDY: To investigate
      the progression of behavioural disturbances in ALS and FTD using the FTD
      functional rating scale (FTDFRS). METHODS: Patients with ALS, FTD-ALS and FTD
      were recruited from specialist clinics. Baseline assessments included the FTDFRS
      and the ALS functional rating scale-revised (ALSFRS-R). Baseline assessments were
      included, as were longitudinal assessments in a proportion of patients. RESULTS:
      In total, 21 ALS, 12 FTD-ALS and 14 behavioural variant FTD (bvFTD) patients were
      included in the study. Moderate or severe behavioural disturbance was common in
      patients with ALS at baseline (47.6%), although less frequent than in bvFTD
      patients; patients with FTD-ALS displayed intermediate impairment. The ALSFRS-R
      showed the opposite pattern and did not correlate with the FTDFRS. During the
      follow-up period, significant (P < 0.05) behavioural deterioration was
      demonstrated in patients with bvFTD and FTD-ALS, with a trend for decline in
      patients with ALS (P = 0.06). CONCLUSION: Motor disturbance is the primary marker
      of disease severity in ALS, but behavioural and functional impairment are common,
      and may decline independently of motor function. As such, the FTDFRS may provide
      valuable information in the assessment and monitoring of ALS.

PMID- 26223150
TI  - Fit to last: Exploring the longevity of the survival processing effect.
AB  - Mounting evidence indicates that processing items for their survival value
      produces superior recall compared to a number of other well-known memory
      enhancing techniques, and that this mnemonic advantage remains up to 48 hours
      after encoding (Raymaekers et al., 2014 ). However, little attention has been
      dedicated to the survival processing effect in location memory, which may
      represent a better test of adaptive memory than retrieval of verbal information.
      The current study aims to fill this gap by exploring the longevity of the
      survival processing effect with both word list (Experiment 1) and location-based
      (Experiment 2) stimuli. Participants rated target items using a single incidental
      encoding scenario, either Survival versus Pleasantness (word stimuli) or Survival
      versus Scavenger Hunt (location stimuli). They were then asked to complete a
      surprise recall task immediately after the ratings and a second recall task 96
      hours later. The results demonstrated that, despite a general reduction in memory
      performance across time, the survival processing advantage was detected at both
      test times for both stimuli types. These findings provide further support for the
      survival processing effect and extend the observed effect duration for both word
      lists and location to 96 hours. 

PMID- 26223149
TI  - Noninvasive Optical Imaging of UV-Induced Squamous Cell Carcinoma in Murine Skin:
      Studies of Early Tumor Development and Vitamin D Enhancement of Protoporphyrin IX
      Production.
AB  - Better noninvasive techniques are needed to monitor protoporphyrin IX (PpIX)
      levels before and during photodynamic therapy (PDT) of squamous cell carcinoma
      (SCC) of the skin. Our aim was to evaluate (1) multispectral fluorescent imaging
      of ultraviolet light (UV)-induced cancer and precancer in a mouse model of SCC
      and (2) multispectral imaging and probe-based fluorescence detection as a tool to
      study vitamin D (VD) effects on aminolevulinic acid (ALA)-induced PpIX synthesis.
      Dorsal skin of hairless mice was imaged weekly during a 24-week UV carcinogenesis
      protocol. Hot spots of PpIX fluorescence were detectable by multispectral imaging
      beginning at 14 weeks of UV exposure. Many hot spots disappeared after cessation
      of UV at week 20, but others persisted or became visible after week 20, and
      corresponded to tumors that eventually became visible by eye. In SCC-bearing mice
      pretreated with topical VD before ALA application, our optical techniques
      confirmed that VD preconditioning induces a tumor-selective increase in PpIX
      levels. Fluorescence-based optical imaging of PpIX is a promising tool for
      detecting early SCC lesions of the skin. Pretreatment with VD can increase the
      ability to detect early tumors, providing a potential new way to improve efficacy
      of ALA-PDT. 

PMID- 26223151
TI  - Duration of priapism is associated with increased corporal oxidative stress and
      antioxidant enzymes in a rat model.
AB  - Ischaemic priapism is characterised by hypoxia, hypercapnia and acidosis with
      resultant corporal fibrosis. Studies reported decreased erectile recovery after
      treatment of priapism longer than 36 h. However, a recent study revealed that
      half of patients with 3 days of priapism achieved recovery after T-shunt,
      although mechanism remains unclear. We aimed to investigate the effect of
      priapism duration on oxidative stress and antioxidant enzymes. Twenty-four male
      rats were divided into four groups. Group 1 served as control. Groups 2, 3 and 4
      represented 1, 2 and 4 h, respectively, of priapism induced by vacuum device and
      rubber band placed at base of erect penis. After 30 min of reperfusion, penectomy
      and blood withdrawal were performed to investigate levels of malondialdehyde
      (MDA), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx). Corporal MDA progressively increased with priapism
      duration (P = 0.01). Corporal SOD significantly differed between groups 1, 2 and
      4. Also, there were significant differences in corporal GPx in groups 1 and 4 (P
      = 0.004) and groups 2 and 4 (P = 0.01). Corporal CAT was higher in group 4, but
      multivariable analysis revealed insignificant differences. Plasma MDA of the
      experimental groups was significantly higher than that of controls. There were no
      differences among groups in terms of other parameters. Increased antioxidant
      enzymes according to duration of priapism suggest that immediate treatment to
      relieve oxidative stress should be initiated in prolonged cases. However, further
      studies should be conducted to determine resistance mechanisms of the corpora to
      prolonged ischaemia.

PMID- 26223152
TI  - Characterization of IS26-composite transposons and multidrug resistance in
      conjugative plasmids from Enterobacter cloacae.
AB  - SHV-12 is the most widespread resistance determinant of Enterobacter cloacae in
      Taiwan; however, blaSHV-12 has rarely been mobilized. Six multidrug-resistant E.
      cloacae isolates were collected. After conjugal transfer, plasmid profiling and
      analysis of incompatibility groups was performed to characterize the genetic
      context of blaSHV-12 -containing fragments. The presence of mobile genetic
      elements was demonstrated by PCR, cloning, sequencing and bioinformatics
      analyses. Four different beta-lactamase genes (blaTEM-1 , blaSHV-12 , blaCTX-M-3
      and/or blaCTX-M-14 ) were observed in the conjugative plasmids belonging to the
      IncHI2 (n = 4), IncI1 or IncP incompatibility groups. The IS26-blaSHV-12 -IS26
      locus was located in five different genetic environments. A novel structural
      organization of a class 1 integron with the aac(6')-IIc cassette truncated by
      IS26 was identified in one isolate. Thus, blaSHV-12 was obtained from different
      plasmids through IS26-mediated homologous recombination. IS26 plays a vital role
      in the distribution of mobile resistance elements between different plasmids
      found in multidrug-resistant E. cloacae isolates.

PMID- 26223153
TI  - Experimental infection by Trypanosoma evansi in sheep: Occurrence of
      transplacental transmission and mice infection by parasite present in the
      colostrum and milk of infected ewes.
AB  - The aims of this study were to evaluate vertical transmission of Trypanosoma
      evansi in sheep experimentally infected, in addition to the mammary transmission
      by colostrum or milk of these infected sheep to mice. Three pregnant sheep were
      used: one uninfected, four months pregnant (Sheep A); and two (Sheep B and C)
      infected intravenously by T. evansi trypomastigotes (4.6*10(6) per animal) on the
      third (Sheep C) and fourth (Sheep B) month of pregnancy. Both infected sheep
      developed low and oscillating parasitemia measured by blood smears. Hemogram was
      performed at seven day intervals, showing anemia, leukocytosis, and lymphocytosis
      on sheep B and C. Three sheep had twins, where sheep A delivered healthy lambs
      and both infected sheep had delivered at least one stillborn. Additionally, lambs
      from sheep B and C died 24 and 72 h post-partum, respectively. Before colostrum
      intake, four lambs from infected sheep were positives for T. evansi according to
      blood smear evaluation, serology (CATT/T. evansi), and PCR. Sheep colostrum and
      milk samples collected from the first four days post-partum were positives for T.
      evansi on PCR, and these samples were able to infect seven mice (out of 10)
      orally (n=4/5) and intraperitoneally (n=3/5). Therefore, we conclude that the
      vertical transmission of T. evansi occurs in pregnant sheep, in addition to a
      strong possibility of the transmission by colostrum and milk.

PMID- 26223154
TI  - FAMACHA(c): A potential tool for targeted selective treatment of chronic
      fasciolosis in sheep.
AB  - The liver fluke Fasciola hepatica causes considerable damage to the health,
      welfare and productivity of ruminants in temperate areas, and its control is
      challenged by anthelmintic resistance. Targeted selective treatment (TST) is an
      increasingly established strategy for preserving anthelmintic efficacy in grazing
      livestock, yet no practical indicators are available to target individuals for
      treatment against fluke infection. This paper evaluates the FAMACHA((c)) system,
      a colour chart for the non-invasive detection of anaemia in small ruminants, for
      this purpose. FAMACHA((c)) scores were collected from 288 sheep prior to
      slaughter during the winter period, when fluke infections were largely mature,
      and condemned livers were recovered and adult flukes extracted. Average
      FAMACHA((c)) score was significantly higher (=paler conjunctivae) in animals
      whose livers were condemned (3.6, n=62) than in those whose livers were not
      condemned (2.1). The number of adult flukes recovered ranged from 2 to 485, and
      was positively correlated with FAMACHA((c)) score (r(2)=0.54, p<0.001). Packed
      cell volume was correlated negatively with both FAMACHA((c)) score (n=240,
      r=0.23, p<0.001) and fluke number (r=0.24, p<0.001). Nematode faecal egg count
      (FEC) did not correlate with FAMACHA((c)) score, and selective treatment of
      individual sheep with FAMACHA((c)) scores above 2 or 3 would have preserved
      between 27 and 100% of nematodes in refugia on the basis of FEC, depending on
      group and the threshold used for treatment. FAMACHA((c)) holds promise as a tool
      for selective treatment of sheep against adult F. hepatica, in support of refugia
      based control of fluke and nematode infections, and further field evaluation is
      warranted. 

PMID- 26223155
TI  - Role of direct-to-consumer genetic testing for complex disease in diagnostics and
      research.

PMID- 26223156
TI  - Benchmarking, key performance indicators and maintaining professional standards
      for cataract surgery in Australia.

PMID- 26223157
TI  - Outcome of children with acute myeloid leukaemia (AML) experiencing primary
      induction failure in the AIEOP AML 2002/01 clinical trial.
AB  - Paediatric patients with acute myeloid leukaemia (AML) who fail induction due to
      primary resistance to chemotherapy account for a significant proportion of cases
      and have a particularly dismal prognosis. We report the clinical and biological
      data, and final outcome of 48 paediatric patients with primary-resistant AML
      enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML
      2002/01 clinical trial. These patients had a significantly higher white blood
      cell count at diagnosis compared to other AML patients. Cytogenetic and molecular
      features did not differ between patients with primary induction failure and
      patients allocated to the high-risk group. For the whole patient population, the
      probability of overall survival, event-free survival (EFS) and disease-free
      survival (DFS) was 21.8% +/- 6.2, 20.4% +/- 5.9, and 49.5% +/- 11.3,
      respectively. Twenty-eight (58%) patients received haematopoietic stem cell
      transplantation (HSCT); 3 were autologous and 25 were allogeneic. Patients who
      underwent HSCT had improved EFS (31.2% vs. 5%, P < 0.0001). Only one of the 20
      patients who did not receive HSCT is alive and disease free. The 19 patients in
      complete remission at time of HSCT showed significantly better DFS than the 9
      with active disease (46% vs. 0%, P = 0.02). This study represents one of the
      largest series with long-term follow up of paediatric AML patients with primary
      refractory disease. Children who underwent transplantation had an encouraging
      long-term outcome. Disease recurrence remains the major cause of treatment
      failure; a better understanding of the disease biology is desirable to develop
      more effective treatment strategies. 

PMID- 26223158
TI  - Graphene-Based Platform for Infrared Near-Field Nanospectroscopy of Water and
      Biological Materials in an Aqueous Environment.
AB  - Scattering scanning near-field optical microscopy (s-SNOM) has emerged as a
      powerful nanoscale spectroscopic tool capable of characterizing individual
      biomacromolecules and molecular materials. However, applications of scattering
      based near-field techniques in the infrared (IR) to native biosystems still await
      a solution of how to implement the required aqueous environment. In this work, we
      demonstrate an IR-compatible liquid cell architecture that enables near-field
      imaging and nanospectroscopy by taking advantage of the unique properties of
      graphene. Large-area graphene acts as an impermeable monolayer barrier that
      allows for nano-IR inspection of underlying molecular materials in liquid. Here,
      we use s-SNOM to investigate the tobacco mosaic virus (TMV) in water underneath
      graphene. We resolve individual virus particles and register the amide I and II
      bands of TMV at ca. 1520 and 1660 cm(-1), respectively, using nanoscale Fourier
      transform infrared spectroscopy (nano-FTIR). We verify the presence of water in
      the graphene liquid cell by identifying a spectral feature associated with water
      absorption at 1610 cm(-1). 

PMID- 26223159
TI  - Fusarium onychomycosis: prevalence, clinical presentations, response to
      itraconazole and terbinafine pulse therapy, and 1-year follow-up in nine cases.
AB  - BACKGROUND: Invasive fusariosis is an infection with Fusarium spp. that primarily
      affects patients with hematologic malignancies and hematopoietic cell transplant
      recipients. Wounds, digital ulcers, onychomycosis, and paronychia are the typical
      cutaneous portals of entry. Early management of mycotic nails in
      immunocompromised and diabetic hosts is crucial to prevent life-threatening
      disease. OBJECTIVES: We report nine cases of Fusarium onychomycosis (F. dimerum,
      n = 5; F. oxysporum, n = 3; Fusarium spp., n = 1) in immunocompetent hosts and
      their response to itraconazole and terbinafine pulse therapy. METHODS: The
      patients received either itraconazole 400 mg daily or terbinafine 500 mg daily
      for 7 d/month; two pulses for fingernails and three pulses for toenails. RESULTS:
      Of the 68 confirmed cases of onychomycosis, eight (11.7%) were Fusarium spp.; the
      ninth patient was culture positive but microscopy negative and responded well to
      itraconazole. Distal subungual onychomycosis was the commonest clinical
      manifestation (seven of nine), one had proximal subungual onychomycosis, and
      total onychodystrophy was noted on four patients. Associated paronychia was
      marked on 66.7% (six of eight) patients. Itraconazole was given to six
      patients/25 nails and terbinafine to three patients/20 nails. All nine patients
      completed treatments, but one defaulted at 12 months follow-up. The efficacy
      parameters were clinical cure (CC) and mycological cure (MC). At month 12 after
      the start of treatment, the response was itraconazole CC 13 of 25 (52%)/MC four
      of six (66.6%) and terbinafine CC four of eight (50%)/MC one of two (50%).
      Recurrence was noted in four of 13 (30.7%) and eight of 13 (61.5%) cured nails in
      the itraconazole group within 3 and 12 months, respectively. CONCLUSIONS:
      Fusarium onychomycosis was clinically indistinguishable from other onychomycosis.
      Both itraconazole and terbinafine pulse therapy were only partially effective on
      Fusarium onychomycosis. Antifungals that are more effective should be sought.

PMID- 26223160
TI  - Myocardial infarction in elderly patients: How to assess their bleeding risk?

PMID- 26223161
TI  - Effects of repeated yohimbine administration on reinstatement of palatable food
      seeking: involvement of dopamine D1 -like receptors and food-associated cues.
AB  - Acute exposure to the pharmacological stressor yohimbine induces relapse to both
      food and drug seeking in a rat model. However, no systematic studies on the
      effects of chronic stress on relapse have been conducted. Because chronic stress
      causes changes in dopamine D1 -like receptor-mediated transmission in prefrontal
      cortex (a relapse node), we tested the hypothesis that chronic exposure to stress
      increases vulnerability to relapse via dopamine-mediated mechanisms.
      Additionally, to determine the role of food-conditioned cues in reinstatement of
      food seeking, we made discrete food-paired cues either available (CS Present) or
      not available (CS Absent) during extinction and reinstatement testing. Rats
      responded for palatable food reinforcers in daily 3-hour sessions, and the
      behavior was extinguished. To model chronic stress, rats were injected daily with
      yohimbine (0.0, 2.5, or 5.0 mg/kg; i.p.) during the first 7 days of extinction.
      Injections were combined with SCH-23390 (0.0, 5.0, or 10.0 ug/kg; i.p.), a D1 
      like receptor antagonist. Rats were then tested for reinstatement of food seeking
      triggered by acute yohimbine (0.0, 1.0, or 2.0 mg/kg; i.p.) and pellet priming.
      Rats treated previously with chronic yohimbine displayed increased responding
      following acute yohimbine priming relative to non-chronically stressed rats, but
      in the CS Absent condition only. Conversely, the lower dose of chronic yohimbine
      caused an increase in pellet-primed reinstatement, but this effect was more
      pronounced in the CS Present condition. Importantly, SCH-23390 combined with
      repeated yohimbine injections attenuated these effects. Thus, chronic stress may
      increase vulnerability to relapse under specific circumstances via a dopamine D1 
      like receptor-mediated mechanism.

PMID- 26223162
TI  - [Factors Associated with Direct Oral Anticoagulants versus Vitamin K Antagonists
      in Patients with Non-valvular Atrial Fibrillation].
AB  - OBJECTIVE: Describing the factors associated with direct oral anticoagulants
      (DOA) prescription in patients with atrial fibrillation (AF). METHOD: This study
      was performed in Toulouse on a cohort of patients received in rhythmology
      consultation, treated with vitamin K antagonists (VKA) or DOA for AF. A
      multivariate model was performed using logistic regression to describe the
      factors associated with DOA prescription and secondly, those associated with
      discontinuation of the anticoagulant. RESULTS: Among the 140 patients included,
      96 (66%) were treated with VKA and 48 (34%) with DOA. Recent AF diagnosis (OR
      7.52, 95% CI [2.41;23.29], p = 0.001), previous exposure to VKA (OR 17.11, 95% CI
      [4.48;60.91], p<0.001), and no current exposure to anti-platelet agents (APA) (OR
      7.69, 95% CI [1.22; 50.00], p = 0.030) were associated to DOA prescription.
      Discontinuation of the anticoagulant (n=24) was associated to DOA intake (OR
      2.71, 95% CI [1.21; 6.08], p = 0.016). DISCUSSION: DOA are less prescribed than
      VKA in patients treated with APA. DOA switch to VKA was not systematic in
      patients diagnosed for a long time. However, international normalized ratio (INR)
      values were stable in most of patients treated with VKA at the switching to DOA.
      A more powerful study would confirm the factors associated with DOA prescription.

PMID- 26223164
TI  - Understanding low caesarean rates.

PMID- 26223163
TI  - [Therapeutic Drug Management for Transplanted Women with a Planned Pregnancy:
      About Two Cases of Lung and Heart-lung Transplantation].
AB  - Advances in lung transplantation allow the women of childbearing age to consider
      becoming mothers. When planning to become pregnant, a therapeutic drug management
      of immunosuppressive drugs and associated therapies is required. It must take
      into account teratogenic and fetotoxic drugs, as well as pharmacokinetic changes
      encountered during pregnancy. Increasingly data are currently available on the
      management of immunosuppressive drugs and associated therapies during pregnancy.
      We report the case management of drug therapy before and during pregnancy in two
      patients after a lung or heart-lung transplantation. To prevent the emergence of
      complications for mother and child, a literature review has been necessary to
      manage drug therapies of each patient. 

PMID- 26223165
TI  - Africa faces a growing threat from neo-colonial alcohol marketing.

PMID- 26223166
TI  - Africa and Latin America: united again.

PMID- 26223167
TI  - One continent--multiple predictions and strategies.

PMID- 26223168
TI  - Response to commentaries.

PMID- 26223169
TI  - 'SBIRT' is the answer? Probably not.

PMID- 26223170
TI  - Bridging the gap between medical settings and specialty addiction treatment.

PMID- 26223171
TI  - Challenges ahead in developing and testing referral to treatment interventions.

PMID- 26223172
TI  - Efficient and final causes of alcohol consumption.

PMID- 26223173
TI  - Response to Tucker & Vuchinich (2015): Behavioral economics in the broader
      context of addiction science.

PMID- 26223174
TI  - Commentary on Jarvis & Feyerabend (2015): A truly smoke-free upbringing, once
      rare, is now commonplace.

PMID- 26223175
TI  - Exploring issues arising from survey non-response.

PMID- 26223176
TI  - Response to Fergusson & Boden (2015): The importance of considering the impacts
      of survey non-participation.

PMID- 26223178
TI  - Prognostic value of human epididymis protein 4 in endometrial cancer and its
      utility for surgical staging.
AB  - AIM: An optimal surgical staging in the group of patients with the high-risk type
      of endometrial cancer is often limited by age and serious internal comorbidities.
      Therefore, in this study we focused on human epididymis protein 4 and its
      contribution to the preoperative differentiation of prognostically distinct
      groups of patients and to individualized surgical treatment as compared with
      cancer antigen (CA) 125 and imaging methods. MATERIAL AND METHODS: The study
      included 115 patients with endometrioid adenocarcinoma diagnosed through
      endometrial biopsy. Before the final operation, blood sampling was performed for
      the determination of human epididymis protein 4 (HE4) and CA125 levels. Serum
      levels of both biomarkers were analyzed in relation to individual prognostic
      factors (stage of disease, depth of myometrial invasion, tumor grade, risk type
      of disease). RESULTS: In the case of HE4, we demonstrated a statistically
      significant difference (P < 0.001) between patients with low and high risk of the
      disease. In our model, achieving the maximum sum of sensitivity and specificity,
      HE4 shows a sensitivity of 72.4% and a specificity of 75.4% for the cut-off 76.5
      pmol/L and is a better predictor in distinguishing the high-risk patients than
      CA125 (area under the curve 0.77 for HE vs 0.71 for CA125). CONCLUSION: HE4 is a
      marker that could complement the findings of imaging techniques and that may be
      useful in decision-making on how to individualize surgical staging. The
      possibility of its introduction as an independent marker in routine practice
      remains, at the moment however, limited. The optimal cut-off for HE4 has not been
      established yet and further studies are needed.

PMID- 26223179
TI  - Kinetics of the cellular intake of a gene expression inducer at high
      concentrations.
AB  - From in vivo single-event measurements of the transient and steady-state
      transcription activity of a single-copy lac-ara-1 promoter in Escherichia coli,
      we characterize the intake kinetics of its inducer (IPTG) from the media. We show
      that the empirical data are well-fit by a model of intake assuming a bilayer
      membrane, with the passage through the second layer being rate-limiting, coupled
      to a stochastic, sub-Poissonian, multi-step transcription process. Using this
      model, we show that for a wide range of extracellular inducer levels (up to 1.25
      mM) the intake process is diffusive-like, suggesting unsaturated membrane
      permeability. Inducer molecules travel from the periplasm to the cytoplasm in, on
      average, 31.7 minutes, strongly affecting cells' response time. The novel
      methodology followed here should aid the study of cellular intake mechanisms at
      the single-event level.

PMID- 26223180
TI  - Interpretation of sequence variants of the FBN1 gene: analog or digital? A
      commentary on decreased frequency of FBN1 missense variants in Ghent criteria
      positive Marfan syndrome and characterization of novel FBN1 variants.

PMID- 26223181
TI  - Genetics of Brugada syndrome.
AB  - The Brugada syndrome is characterized by unique 'coved-type' ST-segment elevation
      in the right precordial leads of electrocardiogram and ventricular fibrillation,
      and is responsible for 4 to 12% of sudden cardiac death in the general
      population. The frequency is higher in Southeast Asia including Japan compared
      with Western countries. Brugada syndrome is an inherited disease usually
      transmitted in an autosomal-dominant manner, and incomplete penetrance is
      frequently seen within affected families. To date, 20 genes have been associated
      with Brugada syndrome, but pathogenic mutations in the genes are identified in
      only about 30% of patients. The genetic background includes mutations in genes
      encoding sodium channel, calcium channels and potassium channels, as well as
      proteins affecting ion channels. Mutations in SCN5A, encoding the cardiac
      predominant sodium channel alpha-subunit, account for 20 to 30% of patients with
      Brugada syndrome and mutations in other genes only account for about 5% of
      patients. Furthermore, a recent genome-wide association study has identified new
      loci associated with the susceptibility of Brugada syndrome. 

PMID- 26223182
TI  - Genetics of autoimmune diseases: insights from population genetics.
AB  - Human genetic diversity is the result of population genetic forces. This genetic
      variation influences disease risk and contributes to health disparities.
      Autoimmune diseases (ADs) are a family of complex heterogeneous disorders with
      similar underlying mechanisms characterized by immune responses against self.
      Collectively, ADs are common, exhibit gender and ethnic disparities, and
      increasing incidence. As natural selection is an important influence on human
      genetic variation, and immune function genes are enriched for signals of positive
      selection, it is thought that the prevalence of AD risk alleles seen in different
      population is partially the result of differing selective pressures (for example,
      due to pathogens). With the advent of high-throughput technologies, new
      analytical methodologies and large-scale projects, evidence for the role of
      natural selection in contributing to the heritable component of ADs keeps
      growing. This review summarizes the genetic regions associated with
      susceptibility to different ADs and concomitant evidence for selection, including
      known agents of selection exerting selective pressure in these regions. Examples
      of specific adaptive variants with phenotypic effects are included as an evidence
      of natural selection increasing AD susceptibility. Many of the complexities of
      gene effects in different ADs can be explained by population genetics phenomena.
      Integrating AD susceptibility studies with population genetics to investigate how
      natural selection has contributed to genetic variation that influences disease
      risk will help to identify functional variants and elucidate biological
      mechanisms. As such, the study of population genetics in human population holds
      untapped potential for elucidating the genetic causes of human disease and more
      rapidly focusing to personalized medicine. 

PMID- 26223184
TI  - Prenatal detection of unilateral nasal airway obstruction caused by a
      dacryocystocele.

PMID- 26223183
TI  - Genetics of congenital heart disease: the contribution of the noncoding
      regulatory genome.
AB  - Congenital heart disease (CHD) is the most common type of birth defect. The
      advent of corrective cardiac surgery and the increase in knowledge concerning the
      longitudinal care of patients with CHD has led to a spectacular increase in life
      expectancy. Therefore, >90% of children with CHD, who survive the first year of
      life, will live into adulthood. The etiology of CHD is complex and is associated
      with both environmental and genetic causes. CHD is a genetically heterogeneous
      disease that is associated with long-recognized chromosomal abnormalities, as
      well as with mutation in numerous (developmental) genes. Nevertheless, the
      genetic factors underlying CHD have remained largely elusive, and it is important
      to realize that in the far majority of CHD patients no causal mutation or
      chromosomal abnormality is identified. However, new insights (alternative
      inheritance paradigms) and technology (next-generation sequencing) have become
      available that can greatly advance our understanding of the genetic factors that
      contribute to CHD; these will be discussed in this review. Moreover, we will
      focus on the discovery of regulatory regions of key (heart) developmental genes
      and the occurrence of variations and mutations within, in the setting of CHD. 

PMID- 26223185
TI  - Predicting formation of adhesions after gynaecological surgery: development of a
      risk score.
AB  - PURPOSE: Risk factors for post-surgical adhesions following gynaecological
      surgery have been identified, but their relative importance has not been
      precisely determined. No practical tool exists to help gynaecological surgeons
      evaluate the risk of adhesions in their patients. The purpose of the study was to
      develop an Adhesion Risk Score to provide a simple tool that will enable
      gynaecological surgeons to routinely quantify the risk of post-surgical adhesions
      in individual patients. METHODS: A group of European gynaecological surgeons
      searched the literature to identify the risk factors and the surgical operations
      reported as carrying a risk of post-surgical adhesions. Through consensus process
      of meetings and communication, a four-point scale was then used by each surgeon
      to attribute a specific weight to each item and collective agreement reached on
      identified risk factors and their relative importance to allow construct of a
      useable risk score. RESULTS: Ten preoperative and 10 intraoperative risk factors
      were identified and weighed, leading to the creation of two sub-scores to
      identify women at risk prior to and during surgery. The Preoperative Risk Score
      can range from 0 to 36, and the Intraoperative Risk Score from 3 to 31. Several
      thresholds between these limits may be used to identify women with low, medium,
      and high risk of post-surgical adhesions. CONCLUSIONS: Gynaecological surgeons
      are encouraged to use this Adhesion Risk Score to identify the risk of adhesions
      in their patients. This will allow better informed use of available resources to
      target preventive measures in women at high risk of post-surgical adhesions.

PMID- 26223186
TI  - DNA damage in spermatozoa from infertile men with varicocele evaluated by sperm
      chromatin dispersion and DBD-FISH.
AB  - PURPOSE: Evaluation of DNA integrity is an important test, possessing greater
      diagnostic and prognostic significance for couples requiring assisted
      reproduction. In this study, we evaluate the levels of DNA damage in infertile
      patients with varicocele with respect to fertile males by the sperm chromatin
      dispersion (SCD) test. The presence of DNA breaks in spermatozoa was confirmed by
      DNA breakage detection-fluorescence in situ hybridization (DBD-FISH). METHODS: In
      this study, the frequency of sperm cells with fragmented DNA was studied in a
      group of 20 infertile patients with varicocele and compared with 20 fertile
      males. The spermatozoa were processed to classify different levels of DNA
      fragmentation using the Halosperm((r)) kit, an improved SCD test, and DBD-FISH.
      RESULTS: Patients with varicocele showed 25.54 +/- 28.17 % of spermatozoa with
      fragmented DNA, significantly higher than those of the group of fertile subjects
      (11.54 +/- 3.88 %). The proportion of degraded cells in total sperm cells with
      fragmented DNA was sixfold higher in the case of patients with varicocele. The
      presence of DNA breaks in spermatozoa was confirmed by DBD-FISH. 5-bp Classical
      satellite-2 regions showed greater sensitivity to damage or "breakage" than
      alphoid satellite regions. CONCLUSIONS: Our finding preliminary demonstrated an
      increase of DNA fragmentation associated to severe sperm damage, in infertile
      patients with varicocele with respect to fertile males. 5-bp Classical satellite
      2 regions showed greater sensitivity to damage or "breakage" than alphoid
      satellite regions.

PMID- 26223187
TI  - Impact of treatment of overactive bladder with anticholinergics on sexual
      function.
AB  - PURPOSE: To establish if an improvement in OAB symptoms by treatment with
      anticholinergics is associated with a corresponding improvement in sexual
      function. METHODS: This was a prospective observational questionnaire study using
      ePAQ-PF (electronic Pelvic Assessment Questionnaire-Pelvic Floor), PISQ 12 and
      PGI-I for overactive bladder and sexual function. Sexually active women with
      overactive bladder were included in the study. Prolapse and voiding dysfunction
      were exclusion criteria for the study. All women were followed up for 6 months
      and were treatment naive. Sexual function before and after treatment was
      compared. The data were analysed using SPSS. Formal ethical approval was
      obtained. RESULTS: 34 women were included in the study. Only 8 % of women
      commenced on anticholinergics had an improvement in sexual function, compared to
      66 % who experienced an improvement in OAB symptoms. Women who did experience a
      benefit in sexual function did so in the first 3 months of treatment of their
      overactive bladder and always noted an improvement in OAB symptoms. CONCLUSIONS:
      Treatment of the overactive bladder symptoms does not guarantee improvement in
      sexual function.

PMID- 26223188
TI  - A Crystal Structure of a Functional RNA Molecule Containing an Artificial
      Nucleobase Pair.
AB  - As one of its goals, synthetic biology seeks to increase the number of building
      blocks in nucleic acids. While efforts towards this goal are well advanced for
      DNA, they have hardly begun for RNA. Herein, we present a crystal structure for
      an RNA riboswitch where a stem C:G pair has been replaced by a pair between two
      components of an artificially expanded genetic-information system (AEGIS), Z and
      P, (6-amino-5-nitro-2(1H)-pyridone and 2-amino-imidazo[1,2-a]-1,3,5-triazin-4
      (8H)-one). The structure shows that the Z:P pair does not greatly change the
      conformation of the RNA molecule nor the details of its interaction with a
      hypoxanthine ligand. This was confirmed in solution by in-line probing, which
      also measured a 3.7 nM affinity of the riboswitch for guanine. These data show
      that the Z:P pair mimics the natural Watson-Crick geometry in RNA in the first
      example of a crystal structure of an RNA molecule that contains an orthogonal
      added nucleobase pair. 

PMID- 26223189
TI  - Relationship between subclinical thyroid dysfunction and the risk of fracture: a
      meta-analysis of prospective cohort studies.
AB  - To identify the relationship between subclinical thyroid dysfunction and the risk
      of fracture, we conducted a meta-analysis of prospective cohort studies. Results
      showed that subclinical hyperthyroidism is associated with an increased risk of
      fracture, especially in elder. INTRODUCTION: There are conflicting data on the
      association between subclinical thyroid dysfunction and the risk of fracture.
      This study is aimed at providing a summary of prospective evidence of the
      relationship between subclinical thyroid dysfunction and the risk of fracture.
      METHODS: We systematically searched the MEDLINE, EMBASE, and the Chinese
      Biomedical literature database (CBM) from 1974 to August 2014 to identify
      prospective cohort studies which have studied the risk of fracture in patients
      with subclinical thyroid dysfunction. Various fractures were reported as the sole
      outcome. RESULTS: Five population-based cohort studies including 314,146
      participants with relationship of endogenous or exogenous subclinical thyroid
      dysfunction or euthyroidism and fractures were identified as eligible for the
      meta-analysis. In an unadjusted model, the relative risk (RR) of subclinical
      hypothyroidism for fracture was 1.30 (CI 1.08-1.56). Risk estimates were lower in
      a multivariable-adjusted model (RR = 1.20, CI 0.70-2.04) and when higher quality
      studies (RR = 0.95, CI 0.58-1.57) were analyzed. For subclinical hyperthyroidism,
      the RR was 1.52 (CI 1.33-1.73) in unadjusted model and 1.25 (CI 1.11-1.41) in a
      multivariable-adjusted model. An analysis of higher quality studies revealed a RR
      1.18 (CI 1.07-1.29). Subgroup analysis indicated that the RR for risk of fracture
      was higher in the endogenous group than the exogenous group, taking thyroid
      altering medicine in subclinical hyperthyroidism. Similar finding was also
      demonstrated in subclinical hypothyroidism. CONCLUSIONS: Despite heterogeneity
      across the studies, data suggest that subclinical hyperthyroidism is associated
      with an increased risk of fracture in the population older than 60 years. No
      evidence could prove a definite association between subclinical hypothyroidism
      and the risk of fracture yet.

PMID- 26223190
TI  - A single CT-guided percutaneous intraosseous injection of thermosensitive
      simvastatin/poloxamer 407 hydrogel enhances vertebral bone formation in
      ovariectomized minipigs.
AB  - The ultimate goal of osteoporosis treatment is prevention of fragile fracture.
      Local treatment targeting specific bone may decrease the incidence of
      osteoporotic fractures. We developed an injectable, thermosensitive
      simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous
      injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The
      greatest hazard associated with osteoporosis is local fragility fractures. An
      adjunct, local treatment might be helpful to decrease the incidence of
      osteoporotic fracture. Studies have found that simvastatin stimulates bone
      formation, but the skeletal bioavailability of orally administered is low.
      Directly delivering simvastatin to the specific bone that is prone to fractures
      may reinforce the target bone and reduce the incidence of fragility fractures.
      METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407
      hydrogel, conducted scanning electron microscopy, rheological, and drug release
      analyses to evaluate the delivery system; injected it into the lumbar vertebrae
      of ovariectomized minipigs via minimally invasive CT-guided percutaneous
      vertebral injection. Three months later, BMD, microstructures, mineral apposition
      rates, and strength were determined by DXA, micro-CT, histology, and
      biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by
      immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective
      controlled delivery system for intraosseous-injected simvastatin. A single
      injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD,
      bone microstructure, and strength; the bone volume fraction and trabecular
      thickness increased nearly 150 %, bone strength almost doubled compared with
      controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and
      osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single
      simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in
      ovariectomized minipigs. The underlying mechanism appears to involve the higher
      expression of VEGF and BMP-2.

PMID- 26223191
TI  - Two models of multiple family therapy in the treatment of adolescent anorexia
      nervosa: a systematic review.
AB  - Multiple family therapy (MFT) is a therapeutic method that brings together
      several families affected by the same pathology. Although from an ideological and
      conceptual point of view, MFT is often linked to family therapy and group
      therapy, it is difficult to define it with precision, a weakness which may in
      turn hinder research on therapeutic effectiveness. This is most notable in the
      field of eating disorders (ED) where, in spite of MFT's great popularity,
      research evidence remains limited. Within the context of a systematic review of
      the literature on MFT in the treatment of anorexia nervosa, the purpose of this
      article is to provide a theoretical and clinical framework for describing two MFT
      models, in an attempt to explore their common and distinct concepts, principles,
      techniques, and factors of change. The first program is a day treatment
      adaptation of the Maudsley family-based MFT approach, developed in Belgium at the
      Therapeutic Centre for Adolescents suffering from Eating Disorders: it focuses on
      the management of ED symptoms, using a strong cognitive behavioral orientation.
      The second is an integrated systemic MFT outpatient and inpatient program carried
      out on the ED unit of a pediatric hospital in Paris, France: it emphasizes intra-
      and inter-family relationships within a systemic framework. Our effort to
      describe and compare these two models constitutes a first step toward determining
      the relative value of different models of MFT. Indeed, each model presents
      specific characteristics that may make it best suited for specific ED populations
      and/or types of families. 

PMID- 26223193
TI  - Phosphorus detection in vitrified bacteria by cryo-STEM annular dark-field
      analysis.
AB  - Bacterial cells often contain dense granules. Among these, polyphosphate bodies
      (PPBs) store inorganic phosphate for a variety of essential functions.
      Identification of PPBs has until now been accomplished by analytical methods that
      required drying or chemically fixing the cells. These methods entail large
      electron doses that are incompatible with low-dose imaging of cryogenic
      specimens. We show here that Scanning Transmission Electron Microscopy (STEM) of
      fully hydrated, intact, vitrified bacteria provides a simple means for mapping of
      phosphorus-containing dense granules based on quantitative sensitivity of the
      electron scattering to atomic number. A coarse resolution of the scattering
      angles distinguishes phosphorus from the abundant lighter atoms: carbon, nitrogen
      and oxygen. The theoretical basis is similar to Z contrast of materials science.
      EDX provides a positive identification of phosphorus, but importantly, the method
      need not involve a more severe electron dose than that required for imaging. The
      approach should prove useful in general for mapping of heavy elements in
      cryopreserved specimens when the element identity is known from the biological
      context. 

PMID- 26223192
TI  - Identification of a novel lymphoid population in the murine epidermis.
AB  - T cell progenitors are known to arise from the foetal liver in embryos and the
      bone marrow in adults; however different studies have shown that a pool of T cell
      progenitors may also exist in the periphery. Here, we identified a lymphoid
      population resembling peripheral T cell progenitors which transiently seed the
      epidermis during late embryogenesis in both wild-type and T cell-deficient mice.
      We named these cells ELCs (Epidermal Lymphoid Cells). ELCs expressed Thy1 and
      CD2, but lacked CD3 and TCRalphabeta/gammadelta at their surface, reminiscent of
      the phenotype of extra- or intra- thymic T cell progenitors. Similarly to
      Dendritic Epidermal T Cells (DETCs), ELCs were radioresistant and capable of self
      renewal. However, despite their progenitor-like phenotype and expression of T
      cell lineage markers within the population, ELCs did not differentiate into
      conventional T cells or DETCs in in vitro, ex vivo or in vivo differentiation
      assays. Finally, we show that ELC expressed NK markers and secreted IFN-gamma
      upon stimulation. Therefore we report the discovery of a unique population of
      lymphoid cells within the murine epidermis that appears related to NK cells with
      as-yet-unidentified functions. 

PMID- 26223195
TI  - Pioneering Metal-Free Oxidative Coupling Strategy of Aromatic Compounds Using
      Hypervalent Iodine Reagents.
AB  - We started our hypervalent iodine research about 30 years ago in the mid-1980s.
      We soon successfully developed the single-electron-transfer oxidation ability of
      a hypervalent iodine reagent, specifically, phenyliodine(III)
      bis(trifluoroacetate) (PIFA), toward aromatic rings of phenyl ethers for forming
      aromatic cation radicals. This was one of the exciting and unexpected events in
      our research studies so far, and the discovery was reported in 1991. It also led
      to the next challenge, developing the metal-free oxidative couplings for C-H
      functionalizations and direct couplings between the C-H bonds of valuable
      aromatic compounds in organic synthesis. In order to realize the effective
      oxidative coupling, pioneering new aromatic ring activations was essential and
      several useful methodologies have been found for oxidizable arenes. The
      achievements regarding this objective obtained in our continuous research are
      herein summarized with classification of the aromatic ring activation strategies.

PMID- 26223194
TI  - MYC Analysis by Fluorescent In Situ Hybridization and Immunohistochemistry in
      Primary Adrenal Angiosarcoma (PAA): a Series of Four Cases.
AB  - Primary adrenal angiosarcomas (PAA) are rare with 36 cases reported in the
      English literature. MYC protein expression and gene amplification have been
      detected in secondary angiosarcoma (AS), and a subset of primary AS. The aim of
      this study was to report the clinicopathologic features of PAA and examine these
      tumors for MYC amplification and protein expression in a small series of four
      cases (resection, n = 4). Three had available material for ancillary studies and
      were investigated for MYC gene abnormalities and protein expression using
      fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC),
      respectively. Tumors occurred in three females and one male with a mean age of 69
      (53-75) years. The sizes ranged from 8.5 to 15 (mean 11.5) cm and were
      epithelioid in morphology. All tumors had prominent necrosis, and the mitotic
      count ranged from 4 to 41/10 high-power fields (HPFs) (mean 20/10 HPFs, *400).
      Immunohistochemically, the tumor cells were positive for CD31 in 4/4 cases, CD34
      in 1/4 cases, and cytokeratin in 4/4 cases. The mean follow-up period was 10.8 (3
      19) months, of which three patients died of disease with distant metastases, and
      one patient was alive with disease. MYC nuclear staining was identified in the
      three cases tested. Two cases showed polysomy of chromosome 8 without MYC
      amplification or rearrangement. Two MYC-positive cases by IHC demonstrated copy
      number gain in chromosome 8, and one MYC-positive case was not associated with a
      chromosome 8/MYC gene abnormality. In the context of new targeted therapies, MYC
      positivity in PAA may be clinically valuable in treating patients with these
      aggressive neoplasms.

PMID- 26223196
TI  - A curable cause of hypertension: renal artery pseudoaneurysm.
AB  - Renal artery aneurysms and pseudoaneurysms are rare vascular abnormalities. These
      anomalies, which are usually asymptomatic, may be associated with hypertension.
      Here, we present the successful treatment of a renal artery pseudoaneurysm in a
      patient with hypertension, with an overview of the literature. 

PMID- 26223198
TI  - Achievement of guideline targets in elderly patients on hemodialysis: a
      multicenter study.
AB  - OBJECTIVES: Advanced age is associated with shorter survival on dialysis. The aim
      of the present study was to compare the adherence with KDOQI guideline targets
      and the association between mortality and satisfying the guidelines targets
      between hemodialysis patients aged 65 years and over and those younger than 65
      years. METHODS: Data were collected using a questionnaire sent to all 46 HD
      centers in Serbia with totally 3868 HD patients. The 24 centers responded and
      sent the data on all patients aged 18 years or older that were on regular HD for
      more than 3 months (2153 patients, 1320 males, aged 18-90 years). Data are
      presented in two groups: a group of patients younger than 65 years (1438, 66.8 %)
      and a group of patients aged 65 years and over (715, 33.2 %). The percentage of
      patients whose values failed to meet the targets recommended by KDOQI Clinical
      Practice Guidelines was calculated for dialysis dose (spKt/V), hemoglobin, serum
      phosphorus, serum calcium and plasma iPTH (150-300 pg/mL). Patients were followed
      from enrollment until their death, kidney transplantation, departure from the
      center or the end of the study. RESULTS: Elderly patients were more likely to
      have hypertension, significantly lower systolic and diastolic blood pressure and
      smaller dialysis vintage than younger patients. They were less frequently treated
      with high-flux membranes and hemodiafiltration and they had significantly lower
      number of dialysis hours per week and significantly lower interdialytic weight
      gain. They used ESA and phosphate binders less frequently than younger patients
      (p < 0.001 and p = 0.002). Older patients had similar Kt/V as younger ones but
      they had significantly more frequent Hb level outside the target range than
      younger patients. During the year follow-up period, by using a Cox proportional
      hazards model it has been confirmed that age, dialysis vintage, weekly dialysis
      time and target values for Kt/V were significant independent predictors of time
      to death for younger patients and gender, dialysis vintage and iPTH were
      independent predictor of time to death for older patients. CONCLUSION: Despite
      less favorable dialysis prescription, older patients had similar Kt/V and less
      frequent deviations from the target values proposed by KDOQI for serum phosphorus
      and iPTH but more frequent deviation for Hb value as compared with younger
      patients. Risk factors for mortality differ between older and younger patients;
      out of five KDOQI targets, only Kt/V proved to be a significant risk factor for
      mortality for younger and iPTH for older patients.

PMID- 26223197
TI  - State-of-the-art biosimilar erythropoietins in the management of renal anemia:
      lessons learned from Europe and implications for US nephrologists.
AB  - The European Medicines Agency (EMA), under a strictly regulated pathway, has
      approved several biosimilar products since 2005, including biosimilar versions of
      the erythropoiesis-stimulating agent (ESA) epoetin alfa since 2007. Subsequent to
      these approvals, the use of biosimilar epoetin alfa in the management of renal
      anemia has grown steadily throughout Europe. With the enactment of the US
      Biologics Price Competition and Innovation Act of 2009, a US Food and Drug
      Administration regulatory approval process for biosimilars was legalized. Thus,
      biosimilar erythropoietin products are expected to be available for prescription
      in the USA by mid-decade, presumably at a price that is competitive with the
      originator brand-name reference products. In this paper, we describe the status
      of originator and biosimilar ESAs, review the clinical development and regulatory
      approval of biosimilar erythropoietins in Europe, and summarize relevant efficacy
      and safety information of biosimilar erythropoietins in relation to their
      reference products to provide a background for US nephrologists as they appraise
      biosimilar erythropoietins as treatment options for renal anemia. Key lessons
      learned from Europe are that (a) EMA-approved biosimilar erythropoietins have
      comparable efficacy and safety profiles to their reference product
      erythropoietin; (b) pharmacovigilance preapproval and postapproval are critical,
      especially with regard to immunogenicity and vascular thromboembolic events; (c)
      strict preapproval and postapproval requirements must guide the regulatory
      pathway for biosimilars; and (d) high-quality manufacturing and production
      processes must be established to ensure quality biosimilar products. The
      availability of biosimilar erythropoietins in the USA will provide nephrologists
      with alternative effective, and potentially more affordable, treatment options
      for patients with renal anemia.

PMID- 26223199
TI  - ExAtlas: An interactive online tool for meta-analysis of gene expression data.
AB  - We have developed ExAtlas, an on-line software tool for meta-analysis and
      visualization of gene expression data. In contrast to existing software tools,
      ExAtlas compares multi-component data sets and generates results for all
      combinations (e.g. all gene expression profiles versus all Gene Ontology
      annotations). ExAtlas handles both users' own data and data extracted semi
      automatically from the public repository (GEO/NCBI database). ExAtlas provides a
      variety of tools for meta-analyses: (1) standard meta-analysis (fixed effects,
      random effects, z-score, and Fisher's methods); (2) analyses of global
      correlations between gene expression data sets; (3) gene set enrichment; (4) gene
      set overlap; (5) gene association by expression profile; (6) gene specificity;
      and (7) statistical analysis (ANOVA, pairwise comparison, and PCA). ExAtlas
      produces graphical outputs, including heatmaps, scatter-plots, bar-charts, and
      three-dimensional images. Some of the most widely used public data sets (e.g.
      GNF/BioGPS, Gene Ontology, KEGG, GAD phenotypes, BrainScan, ENCODE ChIP-seq, and
      protein-protein interaction) are pre-loaded and can be used for functional
      annotations. 

PMID- 26223200
TI  - Knowledge-based reasoning to annotate noncoding RNA using multi-agent system.
AB  - Noncoding RNAs (ncRNAs) have been focus of intense research over the last few
      years. Since characteristics and signals of ncRNAs are not entirely known,
      researchers use different computational tools together with their biological
      knowledge to predict putative ncRNAs. In this context, this work presents ncRNA
      Agents, a multi-agent system to annotate ncRNAs based on the output of different
      tools, using inference rules to simulate biologists' reasoning. Experiments with
      data from the fungus Saccharomyces cerevisiae allowed to measure the performance
      of ncRNA-Agents, with better sensibility, when compared to Infernal, a widely
      used tool for annotating ncRNA. Besides, data of the Schizosaccharomyces pombe
      and Paracoccidioides brasiliensis fungi identified novel putative ncRNAs, which
      demonstrated the usefulness of our approach. NcRNA-Agents can be be found at:
      http://www.biomol.unb.br/ncrna-agents.

PMID- 26223201
TI  - F1FO ATP Synthase Is Expressed at the Surface of Embryonic Rat Heart-Derived H9c2
      Cells and Is Affected by Cardiac-Like Differentiation.
AB  - Taking advantage from the peculiar features of the embryonic rat heart-derived
      myoblast cell line H9c2, the present study is the first to provide evidence for
      the expression of F1FO ATP synthase and of ATPase Inhibitory Factor 1 (IF1) on
      the surface of cells of cardiac origin, together documenting that they were
      affected through cardiac-like differentiation. Subunits of both the catalytic F1
      sector of the complex (ATP synthase-beta) and of the peripheral stalk,
      responsible for the correct F1-FO assembly/coupling, (OSCP, b, F6) were detected
      by immunofluorescence, together with IF1. The expression of ATP synthase-beta,
      ATP synthase-b and F6 were similar for parental and differentiated H9c2, while
      the levels of OSCP increased noticeably in differentiated cells, where the
      results of in situ Proximity Ligation Assay were consistent with OSCP interaction
      within ecto-F1FO complexes. An opposite trend was shown by IF1 whose ectopic
      expression appeared greater in the parental H9c2. Here, evidence for the IF1
      interaction with ecto-F1FO complexes was provided. Functional analyses
      corroborate both sets of data. i) An F1FO ATP synthase contribution to the exATP
      production by differentiated cells suggests an augmented expression of holo-F1FO
      ATP synthase on plasma membrane, in line with the increase of OSCP expression and
      interaction considered as a requirement for favoring the F1-FO coupling. ii) The
      absence of exATP generation by the enzyme, and the finding that exATP hydrolysis
      was largely oligomycin-insensitive, are in line in parental cells with the
      deficit of OSCP and suggest the occurrence of sub-assemblies together evoking
      more regulation by IF1.

PMID- 26223202
TI  - Fetal aortic valve stenosis: a critique of case selection criteria for fetal
      intervention.
AB  - OBJECTIVE: Selection of fetuses with aortic stenosis (AS) for prenatal
      intervention has been influenced by published scoring systems. This study aimed
      to test these scoring systems by retrospective application to consecutive cases
      of fetal AS. METHODS: Retrospective analysis of the echocardiographic findings of
      31 consecutive fetuses with AS evaluated at a tertiary fetal cardiology centre.
      Published 'eHLHS' scores and threshold scores were applied to the group and
      compared to postnatal management, in terms of biventricular repair versus single
      ventricle palliation. RESULTS: Thirty-one fetuses were identified with AS, and
      eHLHS was identified in 17 at the initial echocardiogram. No fetus with a full
      eHLHS score (3/3 or 4/4) achieved a biventricular repair. Three fetuses had a
      favourable threshold score (>=4), one of whom had a successful biventricular
      outcome. Seven fetuses had an unfavourable threshold score (<4) and underwent a
      univentricular pathway. CONCLUSION: The eHLHS score is a reliable predictor for
      the progression to HLHS at term. The score identifies those who would achieve a
      biventricular repair postnatally without prenatal intervention. A minority of
      fetuses with favourable threshold scores may achieve a biventricular repair
      postnatally without prenatal intervention, but eHLHS and an unfavourable
      threshold score (<4) predict a single ventricle pathway postnatally.

PMID- 26223203
TI  - In sickness and in health: A cross-sectional analysis of concordance for
      musculoskeletal pain in 13,507 couples.
AB  - BACKGROUND: Musculoskeletal pain conditions are common and create substantial
      burden for the individual and society. While research has shown concordance
      between couples for risk of some diseases, e.g. heart disease or diabetes, little
      information is available on such effects for musculoskeletal pain conditions. Our
      aims were to investigate the presence of concordance between couples for
      consultations about pain, and to examine theoretical influences on such
      concordance. METHODS: This was a 1-year cross-sectional study of musculoskeletal
      pain consultations in a UK primary care database. In total 27,014 patients
      (13,507 couples) aged between 30 and 74 years were included. The main outcome
      measure was the presence of a musculoskeletal morbidity read code indicating a
      consultation for musculoskeletal conditions (any, back, neck, knee, shoulder,
      foot, osteoarthritis). Logistic regression was used to test associations with
      odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Patients whose
      partner had a musculoskeletal pain consultation were also more likely to consult
      for a musculoskeletal condition (OR 1.22, 95% CI 1.12-1.32). This association was
      found to be strongest for shoulder disorders (OR 1.91, 95% CI 1.06-3.47). No
      significant associations were found for other pain conditions. CONCLUSION:
      Results show that partner concordance is present for consultations for some
      musculoskeletal conditions but not others. Possible explanations for concordance
      include the shared health behaviours between couples leading to potential
      heightened awareness of symptoms. Given the high prevalence of musculoskeletal
      pain within populations, it may be worth considering further the mechanisms that
      explain partner concordance.

PMID- 26223204
TI  - Analysis of iron acquisition and storage-related genes in clinical and non
      clinical strains of Yersinia enterocolitica biovar 1A.
AB  - Possession of mechanisms for iron acquisition and its storage enhances the
      ability of the bacteria to survive in the iron-limiting environment of the host.
      In this study, 81 strains of Yersinia enterocolitica biovar 1A isolated from
      various clinical (n = 51) and non-clinical (n = 30) sources were investigated for
      the presence of the genes related to iron acquisition and storage. Important
      genes which were present in more than 85% of the strains included hasA, foxA,
      bfr, bfd, ftnA, and hmsT as well as the fhuCDB, fepBDGCfesfepA, feoAB, yfuABCD,
      hemPRSTUV, and hmsHFRS gene clusters. Majority of these genes is being reported
      for the first time in biovar 1A strains and showed significant homology with
      genes present in the known pathogenic biovars of Y. enterocolitica. However, no
      significant difference was observed in the distribution of iron acquisition and
      storage-related genes among clinical and non-clinical biovar 1A strains. Thus, it
      may be suggested that the presence of iron acquisition and storage-related genes
      per se might not be responsible for the supposedly better ability of clinical
      biovar 1A strains to cause infections in humans. However, in the backdrop of this
      data, the need to undertake functional studies are highly recommended. 

PMID- 26223205
TI  - Erratum to: Associations Between Glycemic Control, Depressed Mood, Clinical
      Depression, and Diabetes Distress Before and After Insulin Initiation: An
      Exploratory, Post Hoc Analysis.

PMID- 26223206
TI  - Evolution of cytoarchitectural landscapes in the mammalian isocortex: Sirenians
      (Trichechus manatus) in comparison with other mammals.
AB  - The isocortex of several primates and rodents shows a systematic increase in the
      number of neurons per unit of cortical surface area from its rostrolateral to
      caudomedial border. The steepness of the gradient in neuronal number and density
      is positively correlated with cortical volume. The relative duration of
      neurogenesis along the same rostrocaudal gradient predicts a substantial fraction
      of this variation in neuron number and laminar position, which is produced
      principally from layers II-IV neurons. However, virtually all of our quantitative
      knowledge about total and laminar variation in cortical neuron numbers and
      neurogenesis comes from rodents and primates, leaving whole taxonomic groups and
      many intermediate-sized brains unexplored. Thus, the ubiquity in mammals of the
      covariation of longer cortical neurogenesis and increased cortical neuron number
      deriving from cortical layers II-IV is undetermined. To begin to address this
      gap, we examined the isocortex of the manatee using the optical disector method
      in sectioned tissue, and also assembled partial data from published reports of
      the domestic cat brain. The manatee isocortex has relatively fewer neurons per
      total volume, and fewer II-IV neurons than primates with equivalently sized
      brains. The gradient in number of neurons from the rostral to the caudal pole is
      intermediate between primates and rodents, and, like those species, is observed
      only in the upper cortical layers. The cat isocortex (Felis domesticus) shows a
      similar structure. Key species for further tests of the origin, ubiquity, and
      significance of this organizational feature are discussed.

PMID- 26223207
TI  - Impact of Toxigenic Clostridium difficile Colonization on the Risk of Subsequent
      C. difficile Infection in Intensive Care Unit Patients.
AB  - BACKGROUND: Clostridium difficile infection (CDI) in hospitalized patients is
      generally attributed to the current stay, but recent studies reveal high C.
      difficile colonization rates on admission. OBJECTIVE: To determine the rate of
      colonization with toxigenic C. difficile among intensive care unit patients upon
      admission as well as acquired during hospitalization, and the risk of subsequent
      CDI. METHODS: Prospective cohort study from April 15 through July 8, 2013. Adults
      admitted to an intensive care unit within 48 hours of admission to the Johns
      Hopkins Hospital, Baltimore, Maryland, were screened for colonization with
      toxigenic C. difficile. The primary outcome was risk of developing CDI. RESULTS:
      Among 542 patients, 17 (3.1%) were colonized with toxigenic C. difficile on
      admission and an additional 3 patients were found to be colonized during
      hospitalization. Both colonization with toxigenic C. difficile on admission and
      colonization during hospitalization were associated with an increased risk for
      development of CDI (relative risk, 10.29 [95% CI, 2.24-47.40], P=.003; and 15.66
      [4.01-61.08], P<.001, respectively). Using multivariable analysis, colonization
      on admission and colonization during hospitalization were independent predictors
      of CDI (relative risk, 8.62 [95% CI, 1.48-50.25], P=.017; and 10.93 [1.49-80.20],
      P=.019, respectively), while adjusting for potential confounders. CONCLUSIONS: In
      intensive care unit patients, colonization with toxigenic C. difficile is an
      independent risk factor for development of subsequent CDI. Further studies are
      needed to identify populations with higher toxigenic C. difficile colonization
      rates possibly benefiting from screening or avoidance of agents known to promote
      CDI.

PMID- 26223208
TI  - Seminal anti-Mullerian hormone levels during recombinant human follicle
      stimulating hormone treatment in men with idiopathic infertility undergoing
      assisted reproduction cycles.
AB  - A prospective study was designed to investigate the effects of recombinant human
      follicle-stimulating hormone (rhFSH) on seminal anti-Mullerian hormone (AMH)
      levels in men with idiopathic oligoasthenoteratozoospermia (iOAT), researching
      possible relationships between the seminal AMH behavior and the response to the
      treatment. Thirty-nine men who were candidates for intracytoplasmic sperm
      injection (ICSI) because of iOAT were enrolled. Patients were treated on
      alternately days with 150 IU of rhFSH for at least 3 months before assisted
      reproduction cycles. Main outcome measures were seminal AMH concentrations before
      and after rhFSH therapy. After treatment, 16 subjects (responders) showed an
      improvement in their sperm count compared to baseline (7.6 +/- 2.9 vs. 19.3 +/-
      7.7, p < 0.01) whereas 23 men (non-responders) experienced no sperm
      modifications. Baseline seminal AMH concentrations were significantly higher in
      responders than in non-responders (53.0 +/- 30.6 vs. 34.6 +/- 18.5, p < 0.025).
      Following therapy, a greater increase in AMH levels was observed in responders
      compared to non-responders (Delta = 24.8 +/- 36.4 vs. Delta = 6.4 +/- 11.2, p <
      0.028). Seminal AMH levels significantly and positively correlated with sperm
      count (after rhFSH treatment rho = 0.647, p < 0.001). Our study suggests that
      rhFSH improves sperm count in a quota of iOAT men, and the subjects who respond
      to the treatment have higher baseline seminal AMH concentrations than the
      patients who are not responsive. Seminal AMH could be helpful to select those
      infertile men who may benefit from rhFSH treatment. 

PMID- 26223209
TI  - Photoswitching a molecular catalyst to regulate CO2 hydrogenation.
AB  - Inspired by nature's ability to regulate catalysis using physiological stimuli,
      azobenzene was incorporated into Rh(bis)diphosphine CO2 hydrogenation catalysts
      to photoinitiate structural changes to modulate the resulting catalytic activity.
      The rhodium bound diphosphine ligands (P(Ph2)-CH2-N(R)-CH2-P(Ph2)) contain the
      terminal amine of a non-natural amino acid, with the R-group being either beta
      alanine (beta-Ala) or gamma-aminobutyric acid (GABA). For both beta-Ala and GABA
      containing complexes, the carboxylic acids of the amino acids were coupled to the
      amines of diaminoazobenzene, creating a complex consisting of a rhodium bound to
      a photo-responsive tetradentate ligand. The photo-induced cis-trans isomerization
      of the azobenzene-containing complexes imposes structural changes on these
      complexes, as evidenced by NMR studies. We found that the CO2 hydrogenation
      activity for the beta-Ala bound rhodium complex is 40% faster at 27  degrees C
      with the light on, i.e. azobenzene in the cis-conformation (TOF = 16 s(-1)) than
      when the complex was in the dark and the azobenzene in the trans-conformation
      (TOF = 11 s(-1)). In contrast the gamma-aminobutyric acid containing rhodium
      complex has the same rate (TOF ~17 s(-1)) with the azobenzene in either the cis
      or the trans-conformation at 27  degrees C. The corresponding (bis)diphosphine
      complexes without the attached azobenzene were also prepared, characterized, and
      catalytically tested for comparison, and have TOF's of 30 s(-1). Computational
      studies were undertaken to evaluate if the difference in rate between the cis-
      and trans-azobenzene isomers for the beta-Ala bound rhodium complex were due to
      structural differences. These computational investigations revealed major
      structural changes between all cis- and trans-azobenzene structures, but only
      minor structural changes that would be unique to the beta-Ala bound rhodium
      complex. We postulate that the different rates between the cis- and trans
      azobenzene beta-Ala bound containing rhodium complexes are due to subtle changes
      in the bite angle arising from steric strain due to the azobenzene-containing
      tetradentate ligand. This strain alters the hydricity of the subsequent rhodium
      hydride and consequently the rate. 

PMID- 26223210
TI  - Effect of the Ancillary Ligands on the Spectral Properties and G-Quadruplexes DNA
      Binding Behavior: A Combined Experimental and Theoretical Study.
AB  - In an effort to explore the effect of ancillary ligands on the spectral
      properties and overall G-quadruplex DNA binding behavior, two new ruthenium(II)
      complexes [Ru(phen)2 (dppzi)](2+) (1) and [Ru(dmp)2 (dppzi)](2+) (2) (phen=1,10
      phenanthroline, dmp=2,9-dimethyl-1,10-phenanthroline, dppzi=dipyrido[3,2-a:2',3'
      c]phenazine-10,11-imidazole) were prepared. Complex 1 can emit luminescence in
      the absence and presence of G-quadruplexes DNA. However, with -CH3 substituent on
      the 2- and 9-positions of the phen ancillary ligand, no detectable luminescence
      is observed for complex 2 in any organic solvent or in the absence and/or
      presence of G-quadruplex DNA. Experimental and molecular docking studies
      indicated that both complexes interacted with the human telomeric repeat
      AG3(T2AG3)3 (22AG) G-quadruplex with the stoichiometric ratio of 1:1, but the two
      complexes showed different G-quadruplex DNA binding affinity. Complex 1 binds to
      the G-quadruplexes DNA more tightly than complex 2 does. Our results demonstrate
      that methyl groups on the phen ancillary ligand significantly affect the spectral
      properties and the overall DNA binding behavior of the complexes. Such difference
      in spectral properties and DNA binding affinities of these two complexes can be
      reasonably explained by DFT/TD-DFT calculations. This work provides guidance not
      only on exploring the G-quadruplexes DNA binding behavior of complexes, but also
      understanding the unique luminescence mechanism.

PMID- 26223211
TI  - Nuancing insulin's actions in liver through rapid NCOR1 phosphorylation.

PMID- 26223212
TI  - Meaning and ostension in great ape gestural communication.
AB  - It is sometimes argued that while human gestures are produced ostensively and
      intentionally, great ape gestures are produced only intentionally. If true, this
      would make the psychological mechanisms underlying the different species'
      communication fundamentally different, and ascriptions of meaning to chimpanzee
      gestures would be inappropriate. While the existence of different underlying
      mechanisms cannot be ruled out, in fact claims about difference are driven less
      by empirical data than by contested assumptions about the nature of ostensive
      communication. On some accounts, there are no reasons to doubt that great ape
      gestural communication is ostensive. If these accounts are correct, attributions
      of meaning to chimpanzee gestures would be justified. 

PMID- 26223213
TI  - The utility of radiographs prior to pin removal after operative treatment of
      supracondylar humerus fractures in children.
AB  - PURPOSE: To determine the safety, utility, and efficacy of pin removal prior to
      radiographs during the postoperative care of surgically treated displaced
      pediatric supracondylar humerus fractures. METHODS: Retrospective review of 532
      children with supracondylar humerus fractures treated with closed reduction and
      pinning from 2007 to 2012. Group 1: children who had their splint/cast removed
      and radiographs prior to pin removal. Group 2: children with radiographs taken
      after removal. Data recorded and analyzed included: demographic and radiographic
      data at the time of surgery and at final follow-up, including the number of
      radiographs taken prior to pin removal and if pins were ever retained after
      radiographs were performed on the date of intended removal. RESULTS: There was no
      difference between the groups' demographics. The number of postoperative
      radiographs taken prior to pin removal ranged from zero to two. No statistically
      significant change in Baumann's (p = 0.79) or lateral humeral capitellar angles
      (p = 0.19) was noted between the groups. No children in group 1 (0/438) had their
      pins retained after radiographs were taken on the date of intended removal.
      CONCLUSION: Obtaining postoperative radiographs prior to pin removal, although
      commonplace, is not necessary. If fracture stability is noted intraoperatively,
      and there is an uneventful postoperative course, it is safe and effective to
      discontinue immobilization and remove pins prior to X-ray. This is safely done
      without change in alignment or clinical sequelae. Doing so can aid in clinic
      flow, may decrease child anxiety, and limit multiple cast room visits. LEVEL OF
      EVIDENCE: Level III therapeutic study.

PMID- 26223214
TI  - Increased Acetylcholinesterase Expression in Bumble Bees During Neonicotinoid
      Coated Corn Sowing.
AB  - While honey bee exposure to systemic insecticides has received much attention,
      impacts on wild pollinators have not been as widely studied. Neonicotinoids have
      been shown to increase acetylcholinesterase (AChE) activity in honey bees at
      sublethal doses. High AChE levels may therefore act as a biomarker of exposure to
      neonicotinoids. This two-year study focused on establishing whether bumble bees
      living and foraging in agricultural areas using neonicotinoid crop protection
      show early biochemical signs of intoxication. Bumble bee colonies (Bombus
      impatiens) were placed in two different agricultural cropping areas: 1) control
      (>= 3 km from fields planted with neonicotinoid-treated seeds) or 2) exposed
      (within 500 m of fields planted with neonicotinoid-treated seeds), and maintained
      for the duration of corn sowing. As determined by Real Time qPCR, AChE mRNA
      expression was initially significantly higher in bumble bees from exposed sites,
      then decreased throughout the planting season to reach a similar endpoint to that
      of bumble bees from control sites. These findings suggest that exposure to
      neonicotinoid seed coating particles during the planting season can alter bumble
      bee neuronal activity. To our knowledge, this is the first study to report in
      situ that bumble bees living in agricultural areas exhibit signs of neonicotinoid
      intoxication.

PMID- 26223215
TI  - Imprinted silica nanoparticles coated with N-propylsilylmorpholine-4-carboxamide
      for the determination of m-cresol in synthetic and real samples.
AB  - m-Cresol-imprinted silica nanoparticles coated with N-propylsilylmorpholine-4
      carboxamide have been developed that contain specific pockets for the selective
      uptake of m-cresol. Silica nanoparticles were synthesized by a sol-gel process
      followed by functionalization of their surface with N-propylsilylmorpholine-4
      carboxamide. The formation of m-cresol-imprinted silica nanoparticles was
      confirmed by UV-Vis spectrophotometry, infrared spectroscopy, thermogravimetric
      analysis, scanning electron microscopy and transmission electron microscopy.
      Electron microscopic studies revealed the formation of monodispersed imprinted
      silica nanoparticles with spherical shape and an average size of 83 nm. The
      developed nanoparticles were filled in a syringe and used for the extraction of m
      cresol from aqueous samples followed by quantification using high-performance
      liquid chromatography with diode array detection. Various adsorption experiments
      showed that developed m-cresol-imprinted silica nanoparticles exhibited a high
      adsorption capacity and selectivity and offered a fast kinetics for rebinding m
      cresol. The chromatographic quantification was achieved using mobile phase
      consisting of acetonitrile/water (70:30 v/v) at an isocratic flow rate of 1.0
      mL/min using a reversed-phase C18 column and detection at lambdamax = 275 nm. The
      limits of detection and quantification were 1.86 and 22.32 ng/mL, respectively,
      for the developed method. The percent recoveries ranged from 96.66-103.33% in the
      spiked samples. This combination of this nanotechnique with molecular imprinting
      was proved as a reliable, sensitive and selective method for determining the
      target from synthetic and real samples. 

PMID- 26223216
TI  - Erratum to: Preconcentration and determination of lead and cadmium levels in
      blood samples of adolescent workers consuming smokeless tobacco products in
      Pakistan.

PMID- 26223217
TI  - Quantitative analysis of heavy metals in medicinal plants collected from
      environmentally diverse locations in India for use in a novel phytopharmaceutical
      product.
AB  - It is important to monitor the quality of the phytopharmaceutical product as its
      therapeutic potential depends on standardized delivery of active ingredients
      present in the botanical source. Minimal presence of toxic impurities like heavy
      metals (HMs) is warranted to ensure product safety and prevent hazardous health
      impacts. In the present study, conducted as part of the development of a novel
      phytopharmaceutical product, the chemical profile of 13 heavy metals (Fe, Cu, Mn,
      Zn, Ni, Co, Mo, V, Cr, As, Pb, Hg, and Cd) was studied in the whole plant, fruit,
      and rhizome of Bacopa monnieri, Hippophae rhamnoides, and Dioscorea bulbifera,
      respectively, from environmentally diverse regions in India. Most samples had HM
      profiles within permissible limits as established by regulatory authorities, with
      the exception of Cd and Hg in low-altitude regions. This study indicates
      geographical regions in India suitable for procuring raw materials to develop and
      manufacture phytopharmaceutical products. 

PMID- 26223218
TI  - Bioefficacy evaluation and dissipation pattern of nanoformulation versus
      commercial formulation of pyridalyl in tomato (Solanum lycopersicum).
AB  - A study was undertaken to evaluate the decline of the residues of pyridalyl in
      tomatoes grown in two different cultivation systems: open field (conventional
      cultivation) and net house (pot experiment). Field experiment was conducted with
      commercial (10 EC) and nanoformulation of pyridalyl on tomato crop. Tomato plants
      were subjected to pesticide spray, when fruits were close to ripeness. Fruit
      samples were taken periodically and cleaned up using QuEChERS methodology, and
      the residue of pyridalyl was analyzed by ultrahigh-performance liquid
      chromatography (UHPLC). It dissipated in tomato fruit following the first-order
      kinetics. In field, average initial deposit of pyridalyl in tomato was observed
      to be 0.222 and 0.371 MUg g(-1) at recommended and double the recommended
      application rate, respectively, using nanoformulation while it was 0.223 and
      0.393 MUg g(-1) on using commercial formulation, respectively. The half-life
      (t1/2) value of nanopyridalyl in tomato fruit was 2.8 and 3.2 days while for
      commercial formulation, it was 2.5 and 2.6 days for recommended and double the
      recommended dose, respectively. In India, maximum residue limit (MRL) on tomato
      has not been fixed for pyridalyl but its residues were always below European MRLs
      (5 MUg g(-1)) on tomato at both application rates. The results of terminal
      residue showed that pyridalyl residues were below the available MRL. Low residues
      in tomatoes suggested that this pesticide is safe to use under the recommended
      dosage. No statistical differences were observed between the cultivation systems
      in relation to the residue levels of pyridalyl. 

PMID- 26223219
TI  - Spatial and temporal estimation of runoff in a semi-arid microwatershed of
      Southern India.
AB  - In a semi-arid microwatershed of Warangal district in Southern India, daily
      runoff was estimated spatially using Soil Conservation Service (SCS)-curve number
      (CN) method coupled with GIS. The groundwater status in this region is over
      exploited, and precise estimation of runoff is very essential to plan
      interventions for this ungauged microwatershed. Rainfall is the most important
      factor governing runoff, and 75.8% of the daily rainfall and 92.1% of the rainy
      days which occurred were below 25 mm/day. The declines in rainfall and rainy days
      observed in recent years were 9.8 and 8.4%, respectively. The surface runoff
      estimated from crop land for a period of 57 years varied from 0 to 365 mm with a
      mean annual runoff of 103.7 mm or 14.1% of the mean annual rainfall. The mean
      annual runoff showed a significant reduction from 108.7 to 82.9 mm in recent
      years. The decadal variation of annual runoff from crop land over the years
      varied from 49.2 to 89.0% which showed the caution needed while planning
      watershed management works in this microwatershed. Among the four land use land
      cover conditions prevailing in the area, the higher runoff (20% of the mean
      annual rainfall) was observed from current fallow in clayey soil and lower runoff
      of 8.7% from crop land in loamy soil due to the increased canopy coverage. The
      drought years which occurred during recent years (1991-2007) in crop land have
      increased by 3.5%, normal years have increased by 15.6%, and the above normal
      years have decreased by 19.1%. This methodology can be adopted for estimating the
      runoff potential from similar ungauged watersheds with deficient data. It is
      concluded that in order to ensure long-term and sustainable groundwater
      utilization in the region, proper estimation of runoff and implementation of
      suitable water harvesting measures are the need of the hour.

PMID- 26223220
TI  - Dissipation and residues of picoxystrobin in peanut and field soil by QuEChERS
      and HPLC-MS/MS.
AB  - The dissipation and final residues of picoxystrobin in peanut and soil were
      determined by a modified quick, easy, cheap, effective, rugged, and safe
      (QuEChERS) method and high-performance liquid chromatography tandem mass
      spectrometry (HPLC-MS/MS). The dissipation and final residue of picoxystrobin at
      three different provinces (Hebei, Hubei, and Shandong) in China were studied. The
      fortification experiments at three different spiking levels of 0.01, 0.05, and
      0.5 mg kg(-1) in all matrices (soil, peanut seedling, shell, stalk, and kernels)
      were conducted, and the recoveries were 79-114% with relative standard deviations
      of 3-12 (n = 5). The dissipation half-lives of picoxystrobin were 1.5-8.6 days in
      soil, and 2.1-2.8 days in seedlings. The final residues of picoxystrobin in
      supervised field trials were 0.05-6.82 mg kg(-1) in stalk, <=0.381 mg kg(-1) in
      soil, <=0.069 mg kg(-1) in shells, and <=0.005 mg kg(-1) in peanut kernels.
      Considering the final residue levels and the maximum residue limits (MRLs), the
      pre-harvest interval of 14 days was recommended for the safe use of picoxystrobin
      in peanut crop.

PMID- 26223221
TI  - Prevalence of Chronic Pain in a Large Integrated Healthcare Delivery System in
      the U.S.A.
AB  - BACKGROUND: There is a paucity of published data on the prevalence of chronic
      pain conditions within large, integrated healthcare organizations in the U.S.A.
      Such data are essential to inform the development of appropriate treatment
      programs. METHODS: Twenty-five selected pain conditions were used to identify
      patients receiving care within the Henry Ford Health System (HFHS) who were
      enrolled in the Health Alliance Plan (HAP), a subsidiary of HFHS. Patients aged
      >= 18 years, enrolled in HAP in 2010, and having >= 2 encounters, >= 30 days
      apart, with an ICD-9-CM diagnosis code for a pain condition of interest during
      2010 were counted. Variables included in the study were as follows: age, gender,
      body mass index (BMI), and Charlson comorbidity conditions and index score.
      RESULTS: Altogether, 14,784 persons (11.6% of the total adult population) met the
      criteria for having a chronic pain condition. Overall, the study population was
      64.4% female and had mean age (SD) of 61.2 (15.6) years and mean BMI of 31.4
      (7.2) kg/m(2) . Musculoskeletal pain conditions were the most common diagnoses,
      comprising 75.4% of all pain diagnoses. Diabetes and chronic pulmonary disease
      were the most common medical comorbidities. CONCLUSIONS: In this comprehensive
      analysis of 2 years of data from a large, vertically integrated metropolitan
      health system, chronic pain was identified in 12% of adult patients.
      Approximately 75% of chronic pain conditions were musculoskeletal. The triad of
      age >= 60 years, BMI >= 30, and female sex were the most salient demographic
      characteristics of patients with chronic pain conditions. These diagnostic and
      demographic data may be used to inform treatment program development.

PMID- 26223222
TI  - Differences in Relationship Characteristics Between HIV-Negative Male Couples Who
      Used and Did Not Use Substances with Sex.
AB  - Although substance use is linked to HIV seroconversion, little is known about
      male couples substance use with sex. The present study sought to: describe
      whether neither, one, or both partners in the couple used a particular substance
      with sex within or outside their relationship; assess, by substance type used
      with sex, whether relationship factors differed between these groups of couples.
      Dyadic data from 83 behaviorally non-monogamous HIV-negative male couples were
      used with multinomial regression models. Those who used with sex within the
      relationship varied by substance type; outside the relationship, most only had
      one partner who used with sex. Couples with one or both partners who used
      substances with sex within or outside the relationship were more likely to have
      higher commitment to their relationship yet less likely to trust their main
      partner; mixed results were found regarding communication. Further research is
      warranted toward the need for preventive intervention development. 

PMID- 26223223
TI  - The impact of aggregating serogroups in dynamic models of Neisseria meningitidis
      transmission.
AB  - BACKGROUND: Neisseria meningitidis (Nm) is a pathogen of multiple serogroups that
      is highly prevalent in many populations. Serogroups associated with invasive
      meningococcal disease (IMD) in Canada, for example, include A, B, C, W-135, X and
      Y. IMD is a rare but serious outcome of Nm infection, and can be prevented with
      vaccines that target certain serogroups. This has stimulated the development of
      dynamic models to evaluate vaccine impact. However, these models typically
      aggregate the various Nm serogroups into a small number of combined groups,
      instead of modelling each serogroup individually. The impact of aggregation on
      dynamic Nm model predictions is poorly understood. Our objective was to explore
      the impact of aggregation on dynamic model predictions. METHODS: We developed two
      age-structured agent-based models--a 2-strain model and a 4-strain model--to
      simulate vaccination programs in the Canadian setting. The 2-strain model was
      used to explore two different groupings: C, versus all other serogroups combined;
      and B, versus all other serogroups combined. The 4-strain model used the four
      groupings: C, B, Neisseria lactamica, versus all other serogroups combined. We
      compared the predicted impact of monovalent C vaccine, quadrivalent ACWY vaccine
      (MCV-4), and monovalent B vaccine (4CMenB) on the prevalence of serogroup
      carriage under these different models. RESULTS: The 2-strain and 4-strain models
      predicted similar overall impacts of vaccines on carriage prevalence, especially
      with respect to the vaccine-targeted serogroups. However, there were some
      significant quantitative and qualitative differences. Declines in vaccine
      targeted serogroups were more rapid in the 2-strain model than the 4-strain
      model, for both the C and the 4CMenB vaccines. Sustained oscillations, and
      evidence for multiple attractors (i.e., different types of dynamics for the same
      model parameters but different initial conditions), occurred in the 4-strain
      model but not the 2-strain model. Strain replacement was also more pronounced in
      the 4-strain model, on account of the 4-strain model spreading prevalence more
      thinly across groups and thus enhancing competitive interactions. CONCLUSIONS:
      Simplifying assumptions like aggregation of serogroups can have significant
      impacts on dynamic model predictions. Modellers should carefully weigh the
      advantages and disadvantages of aggregation when formulating models for multi
      strain pathogens.

PMID- 26223224
TI  - Should docetaxel be administered earlier in prostate cancer therapy?
AB  - Three randomized studies examining docetaxel early in metastatic prostate cancer
      were recently reported. The CHAARTED and STAMPEDE studies showed a survival
      benefit for docetaxel when started with androgen suppression therapy in men with
      newly diagnosed metastatic prostate cancer. The STAMPEDE study also included men
      with biochemically relapsed prostate cancer. The benefit was a median of 13.6
      months in the CHAARTED study and 10 months in STAMPEDE. The survival benefit in
      CHAARTED was stronger in those with high volume disease. The benefit in STAMPEDE
      was greater in metastatic, rather than biochemically relapsed, prostate cancer.
      The third study, GETUG-AFU 15, was a smaller study without a survival benefit.
      These data have changed how we treat metastatic prostate cancer at our centers,
      as we now offer all men with metastatic castration sensitive prostate cancer
      docetaxel chemotherapy upfront. 

PMID- 26223225
TI  - Comparative investigation of respiratory tract involvement in granulomatosis with
      polyangiitis between PR3-ANCA positive and MPO-ANCA positive cases: a
      retrospective cohort study.
AB  - BACKGROUND: The clinical characteristics of myeloperoxidase antineutrophil
      cytoplasmic antibody (MPO-ANCA) positive granulomatosis with polyangiitis (GPA)
      remain unclear, as does the difference between MPO-ANCA positive GPA and
      proteinase 3 (PR3)-ANCA positive GPA, especially with regard to the details of
      respiratory tract involvement. We investigated the differences in clinical,
      radiological, and histopathological features between PR3-ANCA positive GPA and
      MPO-ANCA positive GPA. METHODS: We retrospectively reviewed 16 patients who were
      newly diagnosed with GPA between December 2000 and July 2014. One patient, who
      was positive for both PR3-ANCA and MPO-ANCA, was excluded. Our review was based
      on the European Medicine Agency (EMA) algorithm. RESULTS: Fifty-six percent of
      GPA patients were positive for PR3-ANCA, 38 % for MPO-ANCA, and the remaining 6 %
      for both. The MPO-ANCA positive group included a greater number of females (67
      %). There were no statistically significant differences in laboratory data,
      symptoms and signs, Birmingham Vasculitis Activity Score, or CT findings between
      the two groups. As for upper respiratory tract involvement, the most common
      manifestation was paranasal sinusitis, whereas lung nodules were most common as
      the lower respiratory tract involvement in both groups. Although the combination
      therapy with prednisone and cyclophosphamide was the most common initial
      treatment in both groups, the relapse rate in MPO-ANCA positive cases was lower
      than that of PR3-ANCA positive cases (17 % and 56 %, respectively). CONCLUSION: A
      high prevalence of MPO-ANCA positive GPA was noted. No significant differences in
      clinico-radiological findings were observed except for the prevalence of relapse
      between the PR3-ANCA positive cases and MPO-ANCA positive cases, suggesting that
      the type of ANCA may be of little help in the diagnosis of GPA. Examination for
      granulomatous findings in the respiratory tract is important, even in MPO-ANCA
      positive cases. There is a need to accumulate more cases and conduct a further
      investigation in the future.

PMID- 26223226
TI  - Misdiagnosed murine typhus in a patient with multiple cerebral infarctions and
      hemorrhage: a case report.
AB  - BACKGROUND: Rickettsias cause a wide spectrum of tick-, flea-, or mite-borne
      infections. Rickettsial infections have no classical manifestations and can often
      lead to encephalitis, which can be fatal if improperly diagnosed. CASE
      PRESENTATION: A 74-year-old male farmer was admitted to the hospital with fevers
      and a headache that had lasted for 10 days, followed by 4 days of
      unconsciousness, and his condition continued to deteriorate. Images showed
      multiple acute lesions in the brain stem, and bilateral cerebral and cerebellar
      hemispheres. He was finally diagnosed with endemic typhus and treated with
      antibiotics that resulted in improvement. CONCLUSION: The present report
      describes a patient with a rickettsial infection and subsequent deterioration to
      coma because of an initial misdiagnosis. Because of the similarity to other
      infectious diseases, physicians should be more vigilant towards the history and
      radiologic results to ensure early detection and avoid complications which may
      prove to be fatal.

PMID- 26223228
TI  - Cognitive biases in response to visual body-related stimuli in eating disorders:
      study protocol for a systematic review and meta-analysis.
AB  - BACKGROUND: Biased processing of body-related information may be linked to the
      development and maintenance of eating disorders (ED). The objective of this
      systematic review will be to examine the occurrence and the extent of cognitive
      biases in response to visual body-related stimuli in individuals with ED and
      individuals with an increased risk to develop ED. METHODS: Studies will be
      identified by searching MEDLINE and PsycINFO. We will include observational and
      experimental studies that examine the association between cognitive biases
      (information processing biases) in response to visual body-related stimuli and
      eating-related pathology in clinical and non-clinical adult samples. In addition
      to database searches, citation tracking will be used. Two reviewers will first
      screen titles and abstracts independently and will then review full texts for
      eligibility. Data extraction will be done independently by two reviewers.
      Conflicts at all levels of screening and extraction will be resolved through
      discussion. Studies will be included if they 1) assess cognitive biases (i.e.,
      attentional biases, memory biases, judgment biases, response biases, and
      interpretation biases) in response to visual body-related stimuli (i.e., pictures
      or photographs of a human body or a human body shape), 2) if they report
      associations between biases and eating-related pathology, 3) if study
      participants are at least 16 years or older, and 4) if no priming task was
      administered prior to the assessment. Descriptive data of studies will also be
      collected. Risk of bias assessment will be undertaken by two independent
      reviewers. Data will be analyzed using random-effects meta-analysis. DISCUSSION:
      This systematic review will synthesize the evidence for cognitive bias in
      response to visual body-related stimuli in individuals with ED and individuals
      with an increased risk of developing an ED. The findings may help to better
      understand information processing in eating-related psychopathology. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42015019165.

PMID- 26223227
TI  - Negative pressure wound therapy use to decrease surgical nosocomial events in
      colorectal resections (NEPTUNE): study protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Surgical site infections (SSIs) are the second most common form of
      nosocomial infection. Colorectal resections have high rates of SSIs secondary to
      the inherently contaminated intraluminal environment. Negative pressure wound
      therapy dressings have been used on primarily closed incisions to reduce surgical
      site infections in other surgical disciplines. No randomized control trials exist
      to support the use of negative pressure wound therapy following elective open
      colorectal resection to reduce surgical site infection. METHODS/DESIGN: In this
      single-center, superiority designed prospective randomized open blinded endpoint
      controlled trial, patients scheduled for a colorectal resection via a laparotomy
      will be considered eligible. Patients undergoing laparoscopic resection will be
      enrolled but only randomized and included if the operation is converted to an
      open procedure. Exclusion criteria are patients receiving an abdominoperineal
      resection or a palliative procedure, as well as pregnant patients and those with
      an adhesive allergy. After informed consent, 300 patients will be randomized to
      the use of a standard adhesive gauze dressing or to a negative pressure wound
      device. Patients will be followed in hospital and reassessed on post-operative
      day 30. The primary outcome measure is SSI within the first 30 post-operative
      days. Secondary outcomes include the length of hospital stay, the number of
      return visits related to a potential or actual SSI, cost, and the need for
      homecare. The primary endpoint analysis follows the intention-to-treat principle.
      DISCUSSION: NEPTUNE is the first randomized controlled trial to investigate the
      role of incisional negative pressure wound therapy in decreasing the rates of
      surgical site infections in the abdominal incisions of patients following an
      elective, open colorectal resection. This low-risk intervention may help decrease
      the morbidity and costs associated with the development of an SSI in our
      patients. TRIAL REGISTRATION: NCT02007018--clinicaltrials.gov; 5 December 2013.

PMID- 26223229
TI  - Immune efficacy of five novel recombinant Bordetella bronchiseptica proteins.
AB  - BACKGROUND: The Gram-negative pathogen Bordetella bronchiseptica causes acute and
      chronic respiratory infection in a variety of animals. Currently, there is no
      vaccine to prevent these infections. To identify useful candidate antigens for
      such a vaccine, five B. bronchiseptica genes including amino acid ATP-binding
      cassette transporter substrate-binding protein (ABC), lipoprotein (PL), outer
      membrane porin protein (PPP), leu/ile/val-binding protein (BPP), and conserved
      hypothetical protein (CHP) were cloned and the recombinant proteins were
      expressed. The immune responses of mice to vaccination with individual
      recombinant proteins were measured. RESULTS: Each of the tested recombinant
      proteins induced a high antibody titer. PPP and PL showed protective indices
      against challenges with B. bronchiseptica. The protection ratios were 62.5 and
      50%, respectively, compared with 12.5% for control vaccinations. The protection
      ratios of ABC, BPP, and CHP were not significantly different from the controls.
      IgG-subtype and cytokine analysis demonstrated that PPP and PL can induce two
      immune responses: a humoral immune response and a cell-mediated immune response.
      The humoral immunity-mediated, Th2-type response dominated. CONCLUSION: The
      identification of PPP and PL, which offer immune-protective potential, identifies
      them as candidates for the development of a diagnostic test or a vaccine for B.
      bronchiseptica.

PMID- 26223230
TI  - Computing all hybridization networks for multiple binary phylogenetic input
      trees.
AB  - BACKGROUND: The computation of phylogenetic trees on the same set of species that
      are based on different orthologous genes can lead to incongruent trees. One
      possible explanation for this behavior are interspecific hybridization events
      recombining genes of different species. An important approach to analyze such
      events is the computation of hybridization networks. RESULTS: This work presents
      the first algorithm computing the hybridization number as well as a set of
      representative hybridization networks for multiple binary phylogenetic input
      trees on the same set of taxa. To improve its practical runtime, we show how this
      algorithm can be parallelized. Moreover, we demonstrate the efficiency of the
      software Hybroscale, containing an implementation of our algorithm, by comparing
      it to PIRNv2.0, which is so far the best available software computing the exact
      hybridization number for multiple binary phylogenetic trees on the same set of
      taxa. The algorithm is part of the software Hybroscale, which was developed
      specifically for the investigation of hybridization networks including their
      computation and visualization. Hybroscale is freely available(1) and runs on all
      three major operating systems. CONCLUSION: Our simulation study indicates that
      our approach is on average 100 times faster than PIRNv2.0. Moreover, we show how
      Hybroscale improves the interpretation of the reported hybridization networks by
      adding certain features to its graphical representation.

PMID- 26223231
TI  - Detection of anaerobic carbon monoxide-oxidizing thermophiles in hydrothermal
      environments.
AB  - Carboxydotrophic anaerobic thermophiles have been isolated from various
      hydrothermal environments and are considered to be important carbon monoxide (CO)
      scavengers or primary producers. However, the ecological factors that influence
      the distribution, abundance and CO-oxidizing activities of these bacteria are
      poorly understood. A previous study detected the carboxydotrophic bacteria
      Carboxydothermus spp. in a hot spring sample and found that they constituted up
      to 10% of the total bacterial cells. In this study, we investigated environmental
      features, potential microbial CO-oxidation activities and the abundance of
      Carboxydothermus spp. in various hot springs to determine environmental factors
      that affect CO oxidizers and to see whether Carboxydothermus spp. are common in
      these environments. We detected potential microbial CO-oxidation activities in
      samples that showed relatively high values of total organic carbon, total
      nitrogen, oxidation-reduction potential and soil-water content. The abundance of
      Carboxydothermus spp. did not correlate with the presence of potential microbial
      CO-oxidation activities; however, Carboxydothermus spp. were detected in a wide
      range of environments, suggesting that these bacteria are widely distributed in
      spite of the relatively low population size. This study implies that thermophilic
      CO oxidizers occur in a wide range of environments and oxidize CO in somewhat
      oxidative environments rich in organic matter. 

PMID- 26223232
TI  - A stepped strategy that aims at the nationwide implementation of the Enhanced
      Recovery After Surgery programme in major gynaecological surgery: study protocol
      of a cluster randomised controlled trial.
AB  - BACKGROUND: Enhanced Recovery After Surgery (ERAS) programmes aim at an early
      recovery after surgical trauma and consequently at a reduced length of
      hospitalisation. This paper presents the protocol for a study that focuses on
      large-scale implementation of the ERAS programme in major gynaecological surgery
      in the Netherlands. The trial will evaluate effectiveness and costs of a stepped
      implementation approach that is characterised by tailoring the intensity of
      implementation activities to the needs of organisations and local barriers for
      change, in comparison with the generic breakthrough strategy that is usually
      applied in large-scale improvement projects in the Netherlands. METHODS: All
      Dutch hospitals authorised to perform major abdominal surgery in gynaecological
      oncology patients are eligible for inclusion in this cluster randomised
      controlled trial. The hospitals that already fully implemented the ERAS programme
      in their local perioperative management or those who predominantly admit
      gynaecological surgery patients to an external hospital replacement care facility
      will be excluded. Cluster randomisation will be applied at the hospital level and
      will be stratified based on tertiary status. Hospitals will be randomly assigned
      to the stepped implementation strategy or the breakthrough strategy. The control
      group will receive the traditional breakthrough strategy with three educational
      sessions and the use of plan-do-study-act cycles for planning and executing local
      improvement activities. The intervention group will receive an innovative stepped
      strategy comprising four levels of intensity of support. Implementation starts
      with generic low-cost activities and may build up to the highest level of
      tailored and labour-intensive activities. The decision for a stepwise increase in
      intensive support will be based on the success of implementation so far. Both
      implementation strategies will be completed within 1 year and evaluated on
      effect, process, and cost-effectiveness. The primary outcome is length of
      postoperative hospital stay. Additional outcome measures are length of recovery,
      guideline adherence, and mean implementation costs per patient. DISCUSSION: This
      study takes up the challenge to evaluate an efficient strategy for large-scale
      implementation. Comparing effectiveness and costs of two different approaches,
      this study will help to define a preferred strategy for nationwide dissemination
      of best practices. TRIAL REGISTRATION: Dutch Trial Register NTR4058.

PMID- 26223234
TI  - Incidence of gastric cancer among patients with gastric precancerous lesions:
      observational cohort study in a low risk Western population.

PMID- 26223233
TI  - Polymorphism in vkorc1 Gene of Natal Multimammate Mice, Mastomys natalensis, in
      Tanzania.
AB  - Resistance of rodents to anticoagulant rodenticides has emerged in several areas
      across the world. Single nucleotide mutations in the vkorc1 gene have been shown
      to elicit various levels of anticoagulant resistance, and these mutations are
      prevalent in several Rattus and Mus musculus populations. In sub-Saharan Africa,
      the Natal multimammate mouse, Mastomys natalensis, is one of the most damaging
      pests to crops, and anticoagulant poisons such as bromadiolone are frequently
      used to control these rodents in agricultural fields. Here, we investigate if
      vkorc1 shows any polymorphism in natural populations of M. natalensis. We
      sequenced the third exon of vkorc1 of 162 M. natalensis captured from 14
      different agricultural sites in Morogoro Region, Tanzania. In addition to 6 SNPs
      in the noncoding flanking region, we detected 3 nonsynonymous SNPs in this exon:
      10 animals (6.2%) carried a Leu108Val variant, 2 animals (1.2%) an Ala140Thr
      variant, and 1 animal (0.6 %) an Arg100His variant, all 3 in heterozygous form.
      Ala140Thr is just one residue from a mutation known to be involved in
      anticoagulant resistance in Rattus and Mus. While in vitro or in vivo experiments
      are needed to link vkorc1 genetic polymorphisms to level of VKOR activity and
      anticoagulant susceptibility, our results suggest that M. natalensis individuals
      may vary in their response to anticoagulant rodenticides. This is the first
      vkorc1 sequence data from a species outside the Rattus or Mus genera, and for the
      first time from a rodent species endemic to Africa. 

PMID- 26223235
TI  - Messenger RNA expression of chicken CLOCK gene in the response to Campylobacter
      jejuni inoculation.
AB  - Campylobacter jejuni (C. jejuni) is a leading cause of human bacterial
      gastroenteritis worldwide. Previous research has shown that circadian rhythm
      plays a critical role in host response to C. jejuni colonization. The CLOCK gene
      is one of the core genes regulating circadian rhythms and shows significant
      expression on 7 d post-C. jejuni inoculation. The objective of this study was to
      investigate temporal and spatial expression of chicken CLOCK gene post-C. jejuni
      inoculation. Cecal and splenic RNA were isolated from 2 distinct chicken breeds
      and used to compare the mRNA expression of CLOCK gene between inoculated and
      noninoculated chickens within each breed and between breeds within each of
      inoculated and noninoculated groups. Our results showed that the CLOCK gene was
      significantly down-regulated at 20 h postinoculation (hpi) in cecum and spleen in
      Jiningbairi chicken. CLOCK gene was significantly down-regulated at 4 and 16 hpi
      and up-regulated at 8 hpi in cecum and spleen in specific pathogen free white
      leghorn noninoculated chicken. The findings suggested that expression of CLOCK
      gene was significantly changed post C. jejuin inoculation. This change was
      affected by genetic background, tissue, and time points postinoculation. 

PMID- 26223236
TI  - Pin Tract Infection Following Correction of Charcot Foot With Static Circular
      Fixation.
AB  - BACKGROUND: The traditional nonsurgical accommodative treatment for diabetes
      associated Charcot foot arthropathy has been unsuccessful in improving the
      quality of life in affected individuals. This has led to the growing interest in
      surgical correction of the acquired deformity with either "super construct"
      internal fixation implants or fine-wire static circular external fixation. The
      use of static circular external fixation without implants has been demonstrated
      to achieve high rates of deformity correction with low complication rates. The
      goal of this investigation was to assess the risk of pin site infection in this
      high-risk patient population. METHODS: Over an 11-year period, 283 consecutive
      diabetic patients underwent single-stage correction of Charcot foot deformity
      with static fine-wire circular external fixation and no internal fixation
      devices. Pin care was minimal. RESULTS: Fifty-nine (20.8%) patients developed
      clinical signs of pin tract infection in at least 1 pin site. Forty-nine occurred
      in patients undergoing surgical correction of deformity in the foot. Eight
      occurred in patients undergoing surgical correction at the ankle level and 2 in
      patients undergoing complex reconstruction for combined foot and ankle deformity.
      Higher rates of pin site infections were observed in patients with osteomyelitis
      present at the time of surgery (25.6%) as compared with patients without evidence
      of infection (17.8%), although the difference was not statistically significant
      (P = .1184). There was no correlation between body mass index and pin site
      infection (P = .288). There was a statistically significant trend (P < .05) for
      higher rates of pin site infection in patients with elevated hemoglobin A1C
      levels. Erythema and drainage resolved in all patients with local pin care and
      empiric oral antibiotic therapy. None of the wires were removed prematurely, and
      all infections resolved following removal of the circular external fixator at the
      scheduled time for removal. CONCLUSIONS: Pin site infection was common following
      surgical correction of the acquired deformity associated with Charcot foot. These
      acquired pin site infections were a nuisance but did not appear to add permanent
      morbidity or require additional surgery to resolve. LEVEL OF EVIDENCE: Level IV,
      retrospective case series.

PMID- 26223237
TI  - Ebola: evaluating vaccines during epidemics.

PMID- 26223238
TI  - Phylogenomics databases for facilitating functional genomics in rice.
AB  - The completion of whole genome sequence of rice (Oryza sativa) has significantly
      accelerated functional genomics studies. Prior to the release of the sequence,
      only a few genes were assigned a function each year. Since sequencing was
      completed in 2005, the rate has exponentially increased. As of 2014, 1,021 genes
      have been described and added to the collection at The Overview of functionally
      characterized Genes in Rice online database (OGRO). Despite this progress, that
      number is still very low compared with the total number of genes estimated in the
      rice genome. One limitation to progress is the presence of functional redundancy
      among members of the same rice gene family, which covers 51.6 % of all non
      transposable element-encoding genes. There remain a significant portion or rice
      genes that are not functionally redundant, as reflected in the recovery of loss
      of-function mutants. To more accurately analyze functional redundancy in the rice
      genome, we have developed a phylogenomics databases for six large gene families
      in rice, including those for glycosyltransferases, glycoside hydrolases, kinases,
      transcription factors, transporters, and cytochrome P450 monooxygenases. In this
      review, we introduce key features and applications of these databases. We expect
      that they will serve as a very useful guide in the post-genomics era of research.

PMID- 26223239
TI  - Gestational Diabetes Mellitus Can Be Prevented by Lifestyle Intervention: The
      Finnish Gestational Diabetes Prevention Study (RADIEL): A Randomized Controlled
      Trial.
AB  - OBJECTIVE: To assess whether gestational diabetes mellitus (GDM) can be prevented
      by a moderate lifestyle intervention in pregnant women who are at high risk for
      the disease. RESEARCH DESIGN AND METHODS: Two hundred ninety-three women with a
      history of GDM and/or a prepregnancy BMI of >=30 kg/m(2) were enrolled in the
      study at <20 weeks of gestation and were randomly allocated to the intervention
      group (n = 155) or the control group (n = 138). Each subject in the intervention
      group received individualized counseling on diet, physical activity, and weight
      control from trained study nurses, and had one group meeting with a dietitian.
      The control group received standard antenatal care. The diagnosis of GDM was
      based on a 75-g, 2-h oral glucose tolerance test at 24-28 weeks of gestation.
      RESULTS: A total of 269 women were included in the analyses. The incidence of GDM
      was 13.9% in the intervention group and 21.6% in the control group ([95% CI 0.40
      0.98%]; P = 0.044, after adjustment for age, prepregnancy BMI, previous GDM
      status, and the number of weeks of gestation). Gestational weight gain was lower
      in the intervention group (-0.58 kg [95% CI -1.12 to -0.04 kg]; adjusted P =
      0.037). Women in the intervention group increased their leisure time physical
      activity more and improved their dietary quality compared with women in the
      control group. CONCLUSIONS: A moderate individualized lifestyle intervention
      reduced the incidence of GDM by 39% in high-risk pregnant women. These findings
      may have major health consequences for both the mother and the child.

PMID- 26223240
TI  - Women With Gestational Diabetes Mellitus Randomized to a Higher-Complex
      Carbohydrate/Low-Fat Diet Manifest Lower Adipose Tissue Insulin Resistance,
      Inflammation, Glucose, and Free Fatty Acids: A Pilot Study.
AB  - OBJECTIVE: Diet therapy in gestational diabetes mellitus (GDM) has focused on
      carbohydrate restriction but is poorly substantiated. In this pilot randomized
      clinical trial, we challenged the conventional low-carbohydrate/higher-fat
      (LC/CONV) diet, hypothesizing that a higher-complex carbohydrate/lower-fat
      (CHOICE) diet would improve maternal insulin resistance (IR), adipose tissue (AT)
      lipolysis, and infant adiposity. RESEARCH DESIGN AND METHODS: At 31 weeks, 12
      diet-controlled overweight/obese women with GDM were randomized to an isocaloric
      LC/CONV (40% carbohydrate/45% fat/15% protein; n = 6) or CHOICE (60%/25%/15%; n =
      6) diet. All meals were provided. AT was biopsied at 37 weeks. RESULTS: After ~7
      weeks, fasting glucose (P = 0.03) and free fatty acids (P = 0.06) decreased on
      CHOICE, whereas fasting glucose increased on LC/CONV (P = 0.03). Insulin
      suppression of AT lipolysis was improved on CHOICE versus LC/CONV (56 vs. 31%, P
      = 0.005), consistent with improved IR. AT expression of multiple proinflammatory
      genes was lower on CHOICE (P < 0.01). Infant adiposity trended lower with CHOICE
      (10.1 +/- 1.4 vs. 12.6 +/- 2%, respectively). CONCLUSIONS: A CHOICE diet may
      improve maternal IR and infant adiposity, challenging recommendations for a
      LC/CONV diet.

PMID- 26223241
TI  - A Scientific Answer to a Scientific Question: The Gender Debate on Intimate
      Partner Violence.
AB  - This article addresses Winstok's critiques and comments on my review and analysis
      of the status of scientific information on intimate partner violence (IPV). I
      present some background on the development of the Revised Conflict Tactics Scales
      (CTS2), an analysis of issues related to the operationalization of gender
      symmetry in IPV, and an evaluation of the hypotheses put forth by Winstok and
      others to explain the multimethod divergence in estimates for IPV gender
      patterns. Happily, we know much more about IPV than we did at the time of the
      creation and publication of the CTS2 in the mid-1990s, and excellent data can be
      brought to bear on many of these hypotheses. A scientific evaluation indicates
      that these hypotheses do not explain all of the data showing multimethod
      divergence. In some cases, these hypotheses have been repeatedly disconfirmed. On
      the other hand, increasing amounts of data indicate that choices regarding the
      operationalization of IPV in surveys have a substantial impact on gender
      patterns. Fairly simply methodological modifications can improve multimethod
      convergence. Evidence-based suggestions for measures showing multimethod
      convergence are provided. The field needs to continue to invest in increasing the
      scientific precision of violence measures.

PMID- 26223242
TI  - Critical Review of Hamby's (2014) Article Titled "Intimate Partner and Sexual
      Violence Research, Scientific Progress, Scientific Challenges, and Gender".
AB  - In a recent article, Hamby advocates the replacement of the "old" Conflict Tactic
      Scales used to measure physical partner violence (PV) with a new measurement
      instrument that represents and supports a thesis that gender use of physical PV
      is asymmetrical rather than symmetrical. This article takes a critical look at
      the logic, assumptions, arguments, examples, interpretations, and conclusions,
      presented in Hamby's article, and in some cases disagrees with them. Furthermore,
      this article uses Hamby's proposals as an opportunity to review and examine core
      issues in the study of perpetration of physical PV, including gender-related
      theoretical and methodological issues.

PMID- 26223243
TI  - [Serious Adverse Drug Reaction and Their Preventability in the Elderly Over 65
      Years].
AB  - AIM: To describe the serious adverse drug reactions (ADR) in elderly subjects
      aged over 65 years and assess their preventability. METHODS: A retrospective
      study was conducted at the Regional Pharmacovigilance Center of Champagne-Ardenne
      (northeast of France) between January and May 2013. Patients aged over 65 years
      who presented a serious ADR notified to the Regional Pharmacovigilance Center
      were included in the study. RESULTS: Over the study period, 100 subjects were
      included in the study. The sex ratio was 0.96. Twenty seven percent of serious
      ADR were preventable. Off-label use accounted for 20% and non-compliance for 5%.
      Bleeding events were the most common serious ADR (36%). The drugs most frequently
      involved in serious ADR were antithrombotic agents (31.4%). CONCLUSION: More than
      a quarter of serious ADR were preventable. Off-label use and non-compliance are
      the main causes identified in the occurrence of preventable serious ADR.

PMID- 26223244
TI  - Bacterial Analysis of Fertilized Eggs of Atlantic Salmon from the Penobscot,
      Naraguagus, and Machias Rivers, Maine.
AB  - Serious losses have occurred at the U.S. Fish and Wildlife Service, Craig Brook
      National Fish Hatchery, East Orland, Maine, among eggs that were taken from
      Atlantic Salmon Salmo salar, which were held as captive broodfish during their
      returns to the Penobscot River, Naraguagus River, and Machias River to spawn.
      Bacterial isolations were attempted from external surfaces and the internal
      contents of individual eggs. Externally and in all cases, Pseudomonas fluorescens
      was the predominant bacterium associated with the surface of all eggs. These
      bacteria were resistant to a surface treatment of 1,667 ppm formalin for 15 min
      and, therefore, the monoclonal nature of P. fluorescens on egg surfaces was
      considered to result from its ability to resist the germicidal activity of
      formalin administered for antifungal treatments. Flavobacterium psychrophilum,
      the cause of bacterial coldwater disease, was isolated from the interior of 23.6,
      18.1, and 29.2% of the dead Atlantic Salmon eggs from Penobscot River egg lots A
      98, A-100, and A-101, respectively, and concentrations of this pathogen ranged
      from 1.0 * 10(3) to >5 * 10(8) CFU per gram of dead egg. Flavobacterium
      psychrophilum was also isolated from 8.3, 26.7, and 10.0% of the dead eggs from
      Naraguagus River egg lots N-158, N-161, and N-163, respectively, in which
      concentrations of this organism ranged from 1.0 * 10(3) to 7.5 * 10(8) CFU per
      gram of egg. This bacterium was also isolated from within 18.3% and 3.3% of the
      dead eggs from Machias River egg lots M-128 and M-142, respectively, and its
      concentrations ranged from 1.0 * 10(3) to 1.5 * 10(8) CFU per gram of egg. The
      finding of F. psychrophilum from within these eggs is indicative of this
      pathogen's widespread and persistent prevalence in Atlantic Salmon in New
      England.

PMID- 26223245
TI  - Non-valvular atrial fibrillation patients with none or one additional risk factor
      of the CHA2DS2-VASc score. A comprehensive net clinical benefit analysis for
      warfarin, aspirin, or no therapy.
AB  - Oral anticoagulation (OAC) to prevent stroke has to be balanced against the
      potential harm of serious bleeding, especially intracranial haemorrhage (ICH). We
      determined the net clinical benefit (NCB) balancing effectiveness and safety of
      no antithrombotic therapy, aspirin and warfarin in AF patients with none or one
      stroke risk factor. Using Danish registries, we determined NCB using various
      definitions intrinsic to our cohort (Danish weights at 1 and 5 year follow-up),
      with risk weights which were derived from the hazard ratio (HR) of death
      following an event, relative to HR of death after ischaemic stroke. When aspirin
      was compared to no treatment, NCB was neutral or negative for both risk strata.
      For warfarin vs no treatment, NCB using Danish weights was neutral where no risk
      factors were present and using five years follow-up. For one stroke risk factor,
      NCB was positive for warfarin vs no treatment, for one year and five year follow
      up. For warfarin vs aspirin use in patients with no risk factors, NCB was
      positive with one year follow-up, but neutral with five year follow-up. With one
      risk factor, NCB was generally positive for warfarin vs aspirin. In conclusion,
      we show a positive overall advantage (i.e. positive NCB) of effective stroke
      prevention with OAC, compared to no therapy or aspirin with one additional stroke
      risk factor, using Danish weights. 'Low risk' AF patients with no additional
      stroke risk factors (i.e.CHA2DS2-VASc 0 in males, 1 in females) do not derive any
      advantage (neutral or negative NCB) with aspirin, nor with warfarin therapy in
      the long run. 

PMID- 26223246
TI  - Proyecto Mama: a lifestyle intervention in overweight and obese Hispanic women: a
      randomised controlled trial--study protocol.
AB  - BACKGROUND: The proportion of women entering pregnancy overweight or obese has
      been rising and, in turn, is associated with adverse maternal and fetal outcomes.
      Gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines
      further increases health risks and has been independently associated with
      postpartum weight retention. Hispanic women are disproportionately affected by
      overweight and obesity, but have had limited access to interventions that promote
      healthy lifestyles due to cultural, socioeconomic, and language barriers.
      Therefore, the overall goal of this randomized controlled trial is to test the
      efficacy of a culturally and linguistically modified, individually-tailored
      lifestyle intervention to reduce excess GWG, increase postpartum weight loss, and
      improve maternal metabolic status among overweight/obese Hispanic women.
      METHODS/DESIGN: Overweight/obese Hispanic women are recruited in early pregnancy
      and randomly assigned to a Lifestyle Intervention (n = 150) or a Comparison
      Health and Wellness (control) intervention (n = 150). Multimodal contacts (i.e.,
      in-person, telephone counseling, and mailed print-based materials) are used to
      deliver the intervention from early pregnancy (12 weeks gestation) to 6 months
      postpartum, with follow-up to 1 year postpartum. Targets of the intervention are
      to achieve IOM Guidelines for GWG and postpartum weight loss; American Congress
      of Obstetrician and Gynecologist guidelines for physical activity; and American
      Diabetes Association guidelines for diet. The intervention draws from Social
      Cognitive Theory and the Transtheoretical Model and includes strategies to
      address the specific social, cultural, and economic challenges faced by low
      income Hispanic women. Assessments are conducted at baseline (~10 weeks
      gestation), mid pregnancy (24-28 weeks gestation), late pregnancy (32-34 weeks
      gestation) and postpartum at 6-weeks, 6-months, and 12-months by bicultural and
      bilingual personnel blinded to the intervention arm. Efficacy is assessed via
      GWG, postpartum weight loss, and biomarkers of glycemic control, insulin
      resistance, and cardiovascular disease risk factors. Changes in physical activity
      and diet are measured via 7-day accelerometer data and 24-h dietary recalls at
      each assessment time period. DISCUSSION: Hispanic women are the fastest growing
      minority group in the U.S. and are disproportionately affected by overweight and
      obesity. This randomised trial uses a high-reach, low-cost strategy that can
      readily be translated into clinical practice in underserved and minority
      populations. TRIAL REGISTRATION: NCT01868230 May 29, 2013.

PMID- 26223247
TI  - Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 26223248
TI  - Has racial difference in cause-specific death improved in older patients with
      late-stage breast cancer?
AB  - BACKGROUND: Research on temporal mortality trends for stage IV breast cancer is
      limited, especially among older patients by race. We evaluated factors associated
      with overall, breast cancer-specific and other-cause mortalities using
      contemporary population data. PATIENTS AND METHODS: Using the Surveillance,
      Epidemiology, and End Results-Medicare linked data, we identified older women (>=
      66 years) with stage IV breast cancer diagnosed in 2002-2009. Overall mortality
      was estimated by the Kaplan-Meier method, compared by log-rank tests, and modeled
      by Cox models. Competing risk analysis was used to evaluate breast cancer
      specific and other-cause mortalities. RESULTS: The median overall survival time
      for non-Hispanic blacks improved from 8.6 months in 2002-2003 to 9.9 months in
      2007-2009, whereas that for non-Hispanic whites improved from 12.1 to 14.8
      months. In the multivariate model, the risk of breast cancer-specific death for
      patients diagnosed in 2007-2009 was significantly lower (P = 0.02), whereas the
      risk of other-cause mortality changed little (P = 0.88) compared with those risks
      for patients diagnosed in 2002-2003. Non-Hispanic blacks had the higher risk of
      both mortality types compared with non-Hispanic whites; a diagnosis time-race
      interaction term was not statistically significant for either cause of death.
      CONCLUSION: Breast cancer-specific mortality among older women modestly improved
      from 2002 to 2009 across all races, but not other-cause mortality. Racial
      disparity in mortality persisted, but did not widen in this period. Efforts
      should be devoted to improving other-cause mortality for all women, with special
      attention toward decreasing breast cancer mortality for non-Hispanic black women.

PMID- 26223249
TI  - Polymorphisms in interleukin 17A gene and coal workers' pneumoconiosis risk in a
      Chinese population.
AB  - BACKGROUND: The interleukin 17A (IL-17A) which is located on chromosome 6p and
      has been linked to chronic inflammation, is an important candidate gene
      conferring coal workers' pneumoconiosis (CWP). The purpose of this study was to
      investigate the genetic association between single nucleotide polymorphisms
      (SNPs) of IL-17A and CWP in a Chinese population. METHODS: We conducted a case
      control study to investigate the role of four common SNPs in the IL-17A gene, and
      evaluated the relationship between these four SNPs and dust-exposure year,
      tobacco smoking and stages of CWP. A total of 1391 subjects was enrolled in this
      study, including 694 subjects in control group and 697 in case group. TaqMan
      based qRT-PCRs were taken to genotype rs2275913, rs3748067, rs4711998, and
      rs8193036 within the IL-17A gene. Luciferase assays were used to determine the
      effects of rs8193036 C > T alleles on the expression of IL-17A. RESULTS:
      Unconditional logistic regression analysis showed that the genotypes of rs3748067
      AA (adjusted OR = 0.43, 95 % CI = 0.23-0.83) and rs8193036 TT (adjusted OR =
      0.59, 95 % CI = 0.40-0.86) were associated with a decreased risk of CWP,
      particularly among subgroups of smokers (adjusted OR =0.34, 95 % CI = 0.13-0.86
      for rs3748076; adjusted OR = 0.41, 95 % CI = 0.23-0.71 for 8193036) and CWP cases
      with stage I (adjusted OR = 0.45, 95 % CI = 0.21-0.98 for rs3748076; adjusted OR
      = 0.46, 95 % CI = 0.28-0.74 for 8193036). Furthermore, the polymorphism of
      rs3748067 significantly reduced the CWP risk among cases with over 27 years of
      dust exposure (adjusted OR = 0.42, 95 % CI = 0.18-0.97). The luciferase assays in
      two cell lines showed that the rs8193036 C > T substitution could reduce the
      expression of IL-17A, which was consistent with the findings of our association
      study. CONCLUSIONS: The rs3748067 G > A and rs8193036 C > T polymorphisms
      decrease CWP risk. These findings could be helpful in identifying individuals at
      decreased risk for CWP and further studies are warranted to validate them.

PMID- 26223250
TI  - Differences in Staphylococcus aureus nasal carriage and molecular characteristics
      among community residents and healthcare workers at Sun Yat-Sen University,
      Guangzhou, Southern China.
AB  - BACKGROUND: The pathogenic potential and commensal nature of Staphylococcus
      aureus allows for easy transmission both within and outside of the hospital
      environment, and nasal carriage may be responsible for some serious infections.
      This study aimed to determine the molecular and epidemiological characteristics
      of nasal colonization by S. aureus in community residents (CR) and healthcare
      workers (HW) at Sun Yat-Sen University, Guangzhou, China. METHODS: A total of 589
      volunteers, both CR (n = 297) and HW (n = 292), were recruited. Each subject
      completed a questionnaire, and specimens were obtained from the anterior nares
      for S. aureus screening. Genotypic analysis included pulsed-field gel
      electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal
      cassette chromosome mec (SCCmec) typing, and virulence gene detection. RESULTS: A
      total of 138 S. aureus isolates were recovered from separate subjects (23.4%,
      138/589), with four isolates showing methicillin resistance (0.7%, 4/589). The
      prevalence of S. aureus carriage was 25.3% (75/297) in CR and 21.6% (63/292) in
      HW. Methicillin-resistant S. aureus (MRSA) were isolated from one CR (0.3%,
      1/297) and three HW (1.0%, 3/292). The most common risk factors for S. aureus
      carriage in CR were being male, age <= 30 years, and nasal cavity cleaning
      habits. Having a household member in the healthcare profession was associated
      with increased risk among HW. Sequence type (ST)188 and ST59 were the most
      prevalent among the 20 observed STs, accounting for 14.6% and 12.2% of all
      isolates, respectively. The four MRSA isolates presented four different STs, with
      one isolate carrying a type IVa SCCmec element and the other three isolates
      containing type III SCCmec. PFGE analysis grouped the 129 isolates into 23
      pulsotypes, with profiles A, N, E, L, and O the most prevalent. The Panton
      Valentine leucocidin gene (pvl) was identified in two of the 138 isolates, while
      57.5% of isolates carried both the Staphylococcus aureus enterotoxin A (sea) and
      enterotoxin B (seb) genes. CONCLUSIONS: These data indicate a low prevalence of
      nasal MRSA carriage but evidence of molecular heterogeneity among S. aureus
      isolates from CR and HW at Sun Yat-Sen University, Guangzhou. Differences in
      epidemiological and molecular characteristics of S. aureus between CR and HW
      populations may be useful for the understanding and prevention of S. aureus
      infection.

PMID- 26223251
TI  - Dehydroandrographolide enhances innate immunity of intestinal tract through up
      regulation the expression of hBD-2.
AB  - BACKGROUND: Dehydroandrographolide (DA) is one of major active components in the
      well-known oriental herbal medicine Andrographis paniculata (Burm.f) Nees which
      belongs to the Acanthaceae family. DA is used for the treatment of infections in
      China. However, DA has not been found to significantly inhibit bacterial and
      viral growth directly. The current study investigates the effect of DA on the
      expression of human beta -defensin-2 (hBD-2) in human intestinal epithelial cells
      and the possible signaling pathways. METHODS: Human intestinal epithelial HCT-116
      cells were incubated with 1-100 MUM DA for 2-24 h. RT-PCR and Western blot were
      used to assess the expression of hBD-2. The specific inhibitors were used and the
      levels of phosphorylation of signaling molecules were detected for dissecting the
      signaling pathways leading to the induction of hBD-2. RESULTS: MTT assay showed
      there was no obvious cytotoxicity for HCT-116 cells by 1-100 MUM DA treatment. RT
      PCR and Western blot assays showed that DA (1-100 MUM) could up-regulate the
      expression of hBD-2, and the effect lasted longer than 24 h. By using SB203580
      and SB202190 (inhibitors of p38), the enhancement of hBD-2 expression were
      significantly attenuated. However, inhibitor of ERK and inhibitor of JNK could
      not block the effect of DA. Furthermore, Western blot found activation of p38 but
      not ERK and JNK in DA-treated HCT-116 cells. CONCLUSION: The results suggested
      that DA enhanced innate immunity of intestinal tract by up-regulating the
      expression of hBD-2 through the p38 MAPK pathways.

PMID- 26223252
TI  - Equalizer reduces SNP bias in Affymetrix microarrays.
AB  - BACKGROUND: Gene expression microarrays measure the levels of messenger
      ribonucleic acid (mRNA) in a sample using probe sequences that hybridize with
      transcribed regions. These probe sequences are designed using a reference genome
      for the relevant species. However, most model organisms and all humans have
      genomes that deviate from their reference. These variations, which include single
      nucleotide polymorphisms, insertions of additional nucleotides, and nucleotide
      deletions, can affect the microarray's performance. Genetic experiments comparing
      individuals bearing different population-associated single nucleotide
      polymorphisms that intersect microarray probes are therefore subject to systemic
      bias, as the reduction in binding efficiency due to a technical artifact is
      confounded with genetic differences between parental strains. This problem has
      been recognized for some time, and earlier methods of compensation have attempted
      to identify probes affected by genome variants using statistical models. These
      methods may require replicate microarray measurement of gene expression in the
      relevant tissue in inbred parental samples, which are not always available in
      model organisms and are never available in humans. RESULTS: By using sequence
      information for the genomes of organisms under investigation, potentially
      problematic probes can now be identified a priori. However, there is no published
      software tool that makes it easy to eliminate these probes from an annotation. I
      present equalizer, a software package that uses genome variant data to modify
      annotation files for the commonly used Affymetrix IVT and Gene/Exon platforms.
      These files can be used by any microarray normalization method for subsequent
      analysis. I demonstrate how use of equalizer on experiments mapping germline
      influence on gene expression in a genetic cross between two divergent mouse
      species and in human samples significantly reduces probe hybridization-induced
      bias, reducing false positive and false negative findings. CONCLUSIONS: The
      equalizer package reduces probe hybridization bias from experiments performed on
      the Affymetrix microarray platform, allowing accurate assessment of germline
      influence on gene expression.

PMID- 26223253
TI  - Intratumoral and peritumoral post-irradiation changes, but not viable tumor
      tissue, may respond to bevacizumab in previously irradiated meningiomas.
AB  - The efficacy of bevacizumab has not been determined for treatment-refractory
      meningiomas. We treated meningiomas with low-dose bevacizumab and compared the
      radiological responses of non-irradiated meningiomas with previously irradiated
      meningiomas. In addition, we assessed intraparenchymal radiation necrosis
      following bevacizumab treatment.Six patients with meningiomas (three anaplastic,
      one atypical, and two grade I) who were previously treated with multiple sessions
      of radiotherapy and subsequently developed perilesional edema were treated with
      bevacizumab. Of six patients, two patients with anaplastic meningiomas developed
      three tumors following radiotherapy, which were defined as non-irradiated tumors.
      There were 12 pre-existing extra-axial tumors that were previously irradiated.
      Some of these tumors demonstrated adjacent intraparenchymal contrast enhancement.
      These tumors were defined as post-irradiated tumors. Four patients had
      intraparenchymal radiation necrosis. Low-dose bevacizumab was administered
      biweekly over 3-6 cycles to all patients.Four tumors decreased in contrast
      enhanced volume, nine tumors were unchanged, and two tumors progressed. Of the
      three non-irradiated tumors, two tumors increased in volume (126 % and 198 %) and
      one tumor was stable (-5 %). The median reduction rates determined by contrast
      volume were -31 % and -71 % in post-irradiated tumors and radiation necrosis,
      respectively. Non-irradiated tumors had a significantly poorer response to
      bevacizumab than post-irradiated tumors and radiation necrosis (p = 0.0013 and p
      = 0.0005, respectively, Tukey-Kramer test).Low-dose bevacizumab did not
      demonstrate efficacy in the treatment of non-irradiated meningiomas. Responses to
      low-dose bevacizumab could be related to its effect on post-irradiation changes,
      rather than its effect on biologically active tumor tissue in post-irradiated
      meningiomas. Radiological responses to low-dose bevacizumab may distinguish
      biologically active tumors from post-irradiation changes in progressive
      meningiomas following radiotherapy. 

PMID- 26223254
TI  - Clinical evaluation of short 6-mm implants alone, short 8-mm implants combined
      with osteotome sinus floor elevation and standard 10-mm implants combined with
      osteotome sinus floor elevation in posterior maxillae: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Nowadays, short dental implants are being increasingly applied in
      extremely resorbed posterior regions. The recent studies have indicated that
      short implants present a similar success rate to conventional implants. It is
      assumed that short implants can avoid additional surgical morbidity and are less
      technically demanding. However, high-quality evidence (>= Ib: evidence from at
      least one randomized controlled trial) on comparing the clinical outcome of short
      implants and longer implants combined with osteotome sinus floor elevation (OSFE)
      technique is limited. METHODS/DESIGN: The proposed study is designed as a
      prospective single-center, three-arm parallel group, randomized controlled trial.
      We plan to enroll 150 patients in need of dental implant treatment in the
      posterior maxilla. The inclusion criteria include: age ? 18 years, partial
      edentulism in the posterior maxilla for at least 3 months from tooth loss,
      residual bone height ranging from 6 to 8 mm, sufficient bone width (>= 6 mm) in
      the edentulous region. The patients will be divided into three groups according
      to a table of random numbers: group 1: short implants (6 mm) alone; group 2:
      short implants (8 mm) combined with osteotome sinus floor elevation (OSFE); group
      3: standard implants (10 mm) combined with OSFE. The assignment will be concealed
      from the clinical operators until the beginning of implant surgery. The outcome
      examiners and patients will be kept blinded to the assignment. Implant survival
      rates, implant success rates, complications, resonance frequency analysis (RFA)
      measurements, marginal bone level, treatment time and patient-reported outcome
      (visual analogue scale for intraoperative discomfort and postoperative pain) will
      be recorded. Clinical re-evaluations will be performed at 12, 24, 36 and 60
      months after crown placement. DISCUSSION: The results of the trial will support
      better decision-making for dental implant treatment in atrophic maxillary ridges.
      If favorable, the use of short implants may avoid adjunct procedures used for
      implant insertion, thus reducing operative time, complexity and postoperative
      discomfort. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02350075
      (registered on 17 February 2015).

PMID- 26223255
TI  - Method for the location of primary wear scars from retrieved metal on metal hip
      replacements.
AB  - BACKGROUND: Retrieved metal-on-metal acetabular cups are valuable resources in
      investigating the wear behaviour of failed hip implants, but adequate methods to
      do so are lacking. To further contribute to addressing this issue, we developed a
      method to detect the in vivo location of the primary wear scar of an explanted
      cup. METHODS: We proposed a new method in which thirteen patients with failed
      metal hip resurfacings were recruited, and their acetabular components retrieved.
      A 3D wear map was generated and the precise location of the primary wear scar in
      each cup was identified using a coordinate measuring machine. This wear scar
      location was noted in relation to the features on the acetabular cup. Having
      identified the location of the wear scar, this 3D positional map was co
      registered to the implant on the patient's pelvic 3D CT scan. RESULTS: Using our
      proposed technique, we were able to demonstrate that the in vivo position of the
      primary wear scar in explanted metal acetabular cups can be variable.
      CONCLUSIONS: This method has utilised existing techniques to better understand
      the three-dimensional properties of wear behaviour, and may be a method which can
      be used in further studies to investigate variables that affect the position of
      the primary wear scar.

PMID- 26223256
TI  - Milk ejection patterns: an intra- individual comparison of breastfeeding and
      pumping.
AB  - BACKGROUND: Milk ejection is a transient episode critical to milk removal and
      women typically have multiple milk ejections during breastfeeding and pumping.
      Recently it was found that milk ejection characteristics such as number of milk
      ejections and periodicity were consistent throughout 12 months of lactation in
      women who expressed their milk with an electric breast pump. It is not known
      whether the stimulation of an infant at the breast influences milk ejection
      patterns or whether this is a programmed event. The aim of this study was to
      compare milk ejection patterns during breastfeeding and expressing milk with an
      electric pump within mothers. METHODS: Twelve lactating mothers with normal milk
      production (502-1356 mL) had milk ejection recorded by measuring the diameter of
      a major milk duct with ultrasound imaging throughout an entire breastfeed and a
      15-min pumping session. Scans were analysed for timing, duration of duct dilation
      and maximum duct diameter. RESULTS: The initial milk ejection defined as the
      first increase in duct diameter was observed earlier during breastfeeding than
      during two phase pumping sessions but was not statistically significant (p =
      .057). There were no significant differences between the duration of the first or
      second milk ejection for mothers when breastfeeding or pumping at their maximum
      comfortable vacuum (p = .18; p = .99). The times taken to reach the peak duct
      diameter, or the first half of the milk ejection were also not found to be
      significantly different between breastfeeding and pumping. CONCLUSION: This study
      suggests that milk ejection patterns remain consistent within individual mothers
      regardless of whether the mother is breastfeeding or expressing milk indicating a
      likelihood of the process either being programmed or innate to the individual.

PMID- 26223257
TI  - A study about the relevance of adding acetylsalicylic acid in primary prevention
      in subjects with type 2 diabetes mellitus: effects on some new emerging
      biomarkers of cardiovascular risk.
AB  - AIM: To evaluate the relevance of adding acetylsalicylic acid (ASA) in primary
      prevention in subjects with type 2 diabetes mellitus. METHODS: 213 patients with
      type 2 diabetes mellitus and hypertension were randomized to amlodipine 5 mg, or
      amlodipine 5 mg + ASA 100 mg for 3 months (Phase A); then, if adequate blood
      pressure control was reached patients terminated the study; otherwise, amlodipine
      was up-titrated to 10 mg/day for further 3 months and compared to amlodipine 10
      mg + ASA 100 mg (Phase B). We assessed at baseline, at the end of Phase A, and at
      the end of Phase B the levels of some new emerging biomarkers of cardiovascular
      risk including: high sensitivity C-reactive protein (Hs-CRP), adiponectin (ADN),
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      myeloperoxidase (MPO), soluble CD40 ligand (sCDL40). RESULTS: Compared to
      baseline, at the end of Phase A, patients treated with amlodipine 5 mg + ASA 100
      mg showed a statistically significant reduction of Hs-CRP (-15.0%), TNF-alpha (
      21.7%), MPO (-9.7%), and sCDL40 (-15.7%), and a statistically significant
      increase of ADN (+15.0%). These values were significantly better than the ones
      obtained with amlodipine alone. Similarly, at the end of Phase B, amlodipine 10
      mg + ASA significantly lowered Hs-CRP (-18.8%), TNF-alpha (-15.0%), MPO (-9.2%),
      and sCDL40 (-20.0%) and increased ADN (+11.8%), with a better effect compared to
      amlodipine alone. CONCLUSION: All biomarkers considered were significantly
      improved by ASA addition. These data suggest that the use of ASA in primary
      prevention could be useful in patients with type 2 diabetes mellitus and
      hypertension. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02064218.

PMID- 26223258
TI  - Visual and Haptic Shape Processing in the Human Brain: Unisensory Processing,
      Multisensory Convergence, and Top-Down Influences.
AB  - Humans are highly adept at multisensory processing of object shape in both vision
      and touch. Previous studies have mostly focused on where visually perceived
      object-shape information can be decoded, with haptic shape processing receiving
      less attention. Here, we investigate visuo-haptic shape processing in the human
      brain using multivoxel correlation analyses. Importantly, we use tangible,
      parametrically defined novel objects as stimuli. Two groups of participants first
      performed either a visual or haptic similarity-judgment task. The resulting
      perceptual object-shape spaces were highly similar and matched the physical
      parameter space. In a subsequent fMRI experiment, objects were first compared
      within the learned modality and then in the other modality in a one-back task.
      When correlating neural similarity spaces with perceptual spaces, visually
      perceived shape was decoded well in the occipital lobe along with the ventral
      pathway, whereas haptically perceived shape information was mainly found in the
      parietal lobe, including frontal cortex. Interestingly, ventrolateral occipito
      temporal cortex decoded shape in both modalities, highlighting this as an area
      capable of detailed visuo-haptic shape processing. Finally, we found haptic shape
      representations in early visual cortex (in the absence of visual input), when
      participants switched from visual to haptic exploration, suggesting top-down
      involvement of visual imagery on haptic shape processing.

PMID- 26223259
TI  - High-Resolution Functional Connectivity Density: Hub Locations, Sensitivity,
      Specificity, Reproducibility, and Reliability.
AB  - Brain regions with high connectivity have high metabolic cost and their
      disruption is associated with neuropsychiatric disorders. Prior neuroimaging
      studies have identified at the group-level local functional connectivity density
      ( L: FCD) hubs, network nodes with high degree of connectivity with neighboring
      regions, in occipito-parietal cortices. However, the individual patterns and the
      precision for the location of the hubs were limited by the restricted
      spatiotemporal resolution of the magnetic resonance imaging (MRI) measures
      collected at rest. In this work, we show that MRI datasets with higher
      spatiotemporal resolution (2-mm isotropic; 0.72 s), collected under the Human
      Connectome Project (HCP), provide a significantly higher precision for hub
      localization and for the first time reveal L: FCD patterns with gray matter (GM)
      specificity >96% and sensitivity >75%. High temporal resolution allowed effective
      0.01-0.08 Hz band-pass filtering, significantly reducing spurious L: FCD effects
      in white matter. These high spatiotemporal resolution L: FCD measures had high
      reliability [intraclass correlation, ICC(3,1) > 0.6] but lower reproducibility
      (>67%) than the low spatiotemporal resolution equivalents. GM sensitivity and
      specificity benchmarks showed the robustness of L: FCD to changes in model
      parameter and preprocessing steps. Mapping individual's brain hubs with high
      sensitivity, specificity, and reproducibility supports the use of L: FCD as a
      biomarker for clinical applications in neuropsychiatric disorders.

PMID- 26223260
TI  - Decoding Concrete and Abstract Action Representations During Explicit and
      Implicit Conceptual Processing.
AB  - Action understanding requires a many-to-one mapping of perceived input onto
      abstract representations that generalize across concrete features. It is debated
      whether such abstract action concepts are encoded in ventral premotor cortex
      (PMv; motor hypothesis) or, alternatively, are represented in lateral
      occipitotemporal cortex (LOTC; cognitive hypothesis). We used fMRI-based
      multivoxel pattern analysis to decode observed actions at concrete and abstract,
      object-independent levels of representation. Participants observed videos of 2
      actions involving 2 different objects, using either an explicit or implicit task
      with respect to conceptual action processing. We decoded concrete action
      representations by training and testing a classifier to discriminate between
      actions within each object category. To identify abstract action representations,
      we trained the classifier to discriminate actions in one object and tested the
      classifier on actions performed on the other object, and vice versa. Region-of
      interest and searchlight analyses revealed decoding in LOTC at both concrete and
      abstract levels during both tasks, whereas decoding in PMv was restricted to the
      concrete level during the explicit task. In right inferior parietal cortex,
      decoding was significant for the abstract level during the explicit task. Our
      findings are incompatible with the motor hypothesis, but support the cognitive
      hypothesis of action understanding.

PMID- 26223263
TI  - Lateral Intermolecular Self-Exchange Reactions for Hole and Energy Transport on
      Mesoporous Metal Oxide Thin Films.
AB  - Intermolecular self-exchange energy and electron-transfer reactions occur without
      a loss of free energy. This behavior can be exploited for energy-transport
      applications when molecules that undergo self-exchange transfer reactions are
      immobilized on a solid support. This Article focuses upon lateral self-exchange
      reactions and the relevant interfacial chemistry that occurs on the mesoporous
      nanocrystalline (anatase) TiO2 thin films that are commonly used in dye
      sensitized solar cells. It has been known for some time that all of the dye
      molecules (termed sensitizers) within such thin films can be reversibly oxidized
      and reduced by lateral self-exchange electron transfer provided that the
      sensitizer surface coverage exceeds a percolation threshold. Under conditions
      where excited-state electron injection into TiO2 is unfavored, lateral
      intermolecular energy-transfer reactions are also known to occur. The self
      exchange rate constants have been quantified by electrochemical, absorption,
      and/or time-resolved anisotropy techniques and understood within the framework of
      Marcus theory. Such analysis reveals that the reorganization energy and the
      electronic coupling are sensitive to the identity of the molecular compound. Time
      resolved anisotropy measurements have shown that lateral charge and energy
      transfer reactions across the TiO2 surface occur in kinetic competition with
      charge recombination and excited-state relaxation, respectively. The extent to
      which lateral self-exchange reactions might be exploited for solar energy
      conversion applications is discussed, as are critical fundamental issues that
      remain unresolved. 

PMID- 26223261
TI  - Resting-State Functional Connectivity of the Locus Coeruleus in Humans: In
      Comparison with the Ventral Tegmental Area/Substantia Nigra Pars Compacta and the
      Effects of Age.
AB  - The locus coeruleus (LC) provides the primary noradrenergic inputs to the
      cerebral cortex. Despite numerous animal studies documenting the functions of the
      LC, research in humans is hampered by the small volume of this midbrain nucleus.
      Here, we took advantage of a probabilistic template, explored the cerebral
      functional connectivity of the LC with resting-state fMRI data of 250 healthy
      adults, and verified the findings by accounting for physiological noise in
      another data set. In addition, we contrasted connectivities of the LC and the
      ventral tegmental area/substantia nigra pars compacta. The results highlighted
      both shared and distinct connectivity of these 2 midbrain structures, as well as
      an opposite pattern of connectivity to bilateral amygdala, pulvinar, and right
      anterior insula. Additionally, LC connectivity to the fronto-parietal cortex and
      the cerebellum increases with age and connectivity to the visual cortex decreases
      with age. These findings may facilitate studies of the role of the LC in arousal,
      saliency responses and cognitive motor control and in the behavioral and
      cognitive manifestations during healthy and disordered aging. Although the first
      to demonstrate whole-brain LC connectivity, these findings need to be confirmed
      with high-resolution imaging.

PMID- 26223262
TI  - Subregional Mesiotemporal Network Topology Is Altered in Temporal Lobe Epilepsy.
AB  - Temporal lobe epilepsy (TLE) is the most frequent drug-resistant epilepsy in
      adults and commonly associated with variable degrees of mesiotemporal atrophy on
      magnetic resonance imaging (MRI). Analyses of inter-regional connectivity have
      unveiled disruptions in large-scale cortico-cortical networks; little is known
      about the topological organization of the mesiotemporal lobe, the limbic
      subnetwork central to the disorder. We generated covariance networks based on
      high-resolution MRI surface-shape descriptors of the hippocampus, entorhinal
      cortex, and amygdala in 134 TLE patients and 45 age- and sex-matched controls.
      Graph-theoretical analysis revealed increased path length and clustering in
      patients, suggesting a shift toward a more regularized arrangement; findings were
      reproducible after split-half assessment and across 2 parcellation schemes.
      Analysis of inter-regional correlations and module participation showed increased
      within-structure covariance, but decreases between structures, particularly with
      regards to the hippocampus and amygdala. While higher clustering possibly
      reflects topological consequences of axonal sprouting, decreases in
      interstructure covariance may be a consequence of disconnection within limbic
      circuitry. Preoperative network parameters, specifically the segregation of the
      ipsilateral hippocampus, predicted long-term seizure freedom after surgery.

PMID- 26223264
TI  - Predicting the combined effect of multiple genetic variants.
AB  - BACKGROUND: Many genetic variants have been identified in the human genome. The
      functional effects of a single variant have been intensively studied. However,
      the joint effects of multiple variants in the same genes have been largely
      ignored due to their complexity or lack of data. This paper uses HMMvar, a hidden
      Markov model based approach, to investigate the combined effect of multiple
      variants from the 1000 Genomes Project. Two tumor suppressor genes, TP53 and
      phosphatase and tensin homolog (PTEN), are also studied for the joint effect of
      compensatory indel variants. RESULTS: Results show that there are cases where the
      joint effect of having multiple variants in the same genes is significantly
      different from that of a single variant. The deleterious effect of a single indel
      variant can be alleviated by their compensatory indels in TP53 and PTEN. Compound
      mutations in two genes, beta-MHC and MyBP-C, leading to severer cardiovascular
      disease compared to single mutations, are also validated. CONCLUSIONS: This paper
      extends the functionality of HMMvar, a tool for assigning a quantitative score to
      a variant, to measure not only the deleterious effect of a single variant but
      also the joint effect of multiple variants. HMMvar is the first tool that can
      predict the functional effects of both single and general multiple variations on
      proteins. The precomputed scores for multiple variants from the 1000 Genomes
      Project and the HMMvar package are available at
      https://bioinformatics.cs.vt.edu/zhanglab/HMMvar/.

PMID- 26223265
TI  - Effectiveness of a training program in compliance with recommendations for venous
      lines care.
AB  - BACKGROUND: The impact of training programs on the care and maintenance of venous
      lines (VL) has been assessed mainly in patients admitted to the intensive care
      unit (ICU). Data on the impact of such programs in a whole general hospital are
      scarce. The objective of this study was to assess compliance with VL care after
      an extensive training program aimed at nurses caring for adult ICU and non-ICU
      patients. METHODS: We performed 2 point prevalence studies in a general hospital.
      A specialized nurse visited all hospitalized adult patients, performed a bedside
      inspection, and reviewed the nursing records for patients with a VL before and
      after a 1-year training program. The program included an interactive on-line
      teaching component and distribution of pocket leaflets and posters with
      recommendations on VL care. RESULTS: Data recorded for the first and second
      prevalence studies were as follows: number of patients visited, 753 vs. 682;
      total number of patients with >= 1 VL implanted on the visit day, 653 (86.7%) vs
      585 (85.8%); catheters considered unnecessary on the study day, 183 (22.9%) vs 48
      (7.1%) (p < 0.001); number of catheters with local clinical evidence of infection
      on the study day, 18 (2.2%) vs 12 (1.8%) (p = 0.52); registration of insertion
      day (42.3% vs 50.1%; p = 0.003); and registration of day of dressing change
      (41.2% vs 49.1%; p = 0.003). Maintenance parameters improved more in non-ICU than
      in ICU patients. CONCLUSION: A multidisciplinary teaching program to improve VL
      care and compliance with recommendations is effective. Point prevalence studies
      are easy to carry out and effective at demonstrating increases in compliance,
      mainly in non-ICU patients.

PMID- 26223267
TI  - Development of a PCR Assay Based on a Single-Base Pair Substitution for the
      Detection of Aeromonas caviae by Targeting the gyrB Gene.
AB  - Aeromonas caviae is a bacterial pathogen that causes various infectious diseases
      in both humans and animals. To facilitate its detection, we developed species
      specific primer sets targeting polymorphisms in the gyrB gene for use in a PCR
      assay. The technique was able to detect 100% (29/29) of the A. caviae strains
      tested using either of two sets of primers (designated ACF1-ACR and ACF3-ACR),
      which produced 293-bp and 206-bp amplicons, respectively. Another set of primers
      (designated ACF2-ACR) yielded a 237-bp amplicon and exhibited 90% (26/29)
      positive results with respect to A. caviae. None of the primer sets exhibited
      cross-reactivity with 12 non-A. caviae isolates and 52 other non-Aeromonas
      bacteria. The detection limit using the ACF2-ACR and ACF3-ACR primer sets in pure
      culture was 1.6 * 10(3) CFU/mL, or 6 CFU per reaction, whereas that of the ACF1
      ACR primer set was 1.6 * 10(4) CFU/mL, or 60 CFU per reaction. In the case of
      spiked Nile Tilapia Oreochromis niloticus, the sensitivity of all primer sets
      without enrichment was 1.8 * 10(4) CFU/g, or 30 CFU per reaction. Primer set ACF3
      ACR was the best for a PCR assay targeting the gyrB gene, and the PCR technique
      developed was rapid, specific, and sensitive for the identification of A. caviae.

PMID- 26223266
TI  - Evolutionary analysis of selective constraints identifies ameloblastin (AMBN) as
      a potential candidate for amelogenesis imperfecta.
AB  - BACKGROUND: Ameloblastin (AMBN) is a phosphorylated, proline/glutamine-rich
      protein secreted during enamel formation. Previous studies have revealed that
      this enamel matrix protein was present early in vertebrate evolution and
      certainly plays important roles during enamel formation although its precise
      functions remain unclear. We performed evolutionary analyses of AMBN in order to
      (i) identify residues and motifs important for the protein function, (ii) predict
      mutations responsible for genetic diseases, and (iii) understand its molecular
      evolution in mammals. RESULTS: In silico searches retrieved 56 complete sequences
      in public databases that were aligned and analyzed computationally. We showed
      that AMBN is globally evolving under moderate purifying selection in mammals and
      contains a strong phylogenetic signal. In addition, our analyses revealed codons
      evolving under significant positive selection. Evidence for positive selection
      acting on AMBN was observed in catarrhine primates and the aye-aye. We also found
      that (i) an additional translation initiation site was recruited in the ancestral
      placental AMBN, (ii) a short exon was duplicated several times in various species
      including catarrhine primates, and (iii) several polyadenylation sites are
      present. CONCLUSIONS: AMBN possesses many positions, which have been subjected to
      strong selective pressure for 200 million years. These positions correspond to
      several cleavage sites and hydroxylated, O-glycosylated, and phosphorylated
      residues. We predict that these conserved positions would be potentially
      responsible for enamel disorder if substituted. Some motifs that were previously
      identified as potentially important functionally were confirmed, and we found
      two, highly conserved, new motifs, the function of which should be tested in the
      near future. This study illustrates the power of evolutionary analyses for
      characterizing the functional constraints acting on proteins with yet
      uncharacterized structure.

PMID- 26223270
TI  - Depression in multiple sclerosis: The utility of common self-report instruments
      and development of a disease-specific measure.
AB  - The ultimate objective of the present investigation was to improve the detection
      of depression in multiple sclerosis (MS) by comparing common self-report
      depression measures to a new, modified measure, which takes into account the
      contribution that symptoms of MS may have on individuals' reports. There has been
      a longstanding concern regarding the accurate assessment of depression in MS,
      particularly with regard to the overlap of MS symptomatology and neurovegetative
      depression symptoms on self-report questionnaires, which may lead to an
      overdiagnosis of depression in MS. To address these difficulties, we previously
      proposed a "trunk and branch" of depression in MS. This model allows for the
      delineation of what symptoms are most reflective of depression in MS. By
      identifying these symptoms, it was possible to develop a modified Beck Depression
      Inventory (BDI) in which only the items found to be most related to depression in
      MS are included in the new measure, the MS Specific BDI (MS-BDI). We compared
      this measure to common self-report instruments (Beck Depression Inventory-Second
      Edition, BDI-II; Beck Depression Inventory-Fast Screen, BDI-FS; Chicago
      Multiscale Depression Inventory, CMDI). Results suggest that cutoffs of 4 on the
      BDI-FS and 23 on the CMDI Mood subscale are most useful when screening for
      depression in MS, with a sensitivity for both of 100%, while a cutoff of 19 on
      the BDI-II, a cutoff of 22 on the CMDI Evaluative scale, and a cutoff of 8 on the
      MS-BDI had high specificities, suggesting they can be used as to assist in
      diagnosing depression in MS. 

PMID- 26223268
TI  - The role of Alu elements in the cis-regulation of RNA processing.
AB  - The human genome is under constant invasion by retrotransposable elements. The
      most successful of these are the Alu elements; with a copy number of over a
      million, they occupy about 10 % of the entire genome. Interestingly, the vast
      majority of these Alu insertions are located in gene-rich regions, and one-third
      of all human genes contains an Alu insertion. Alu sequences are often embedded in
      gene sequence encoding pre-mRNAs and mature mRNAs, usually as part of their
      intron or UTRs. Once transcribed, they can regulate gene expression as well as
      increase the number of RNA isoforms expressed in a tissue or a species. They also
      regulate the function of other RNAs, like microRNAs, circular RNAs, and
      potentially long non-coding RNAs. Mechanistically, Alu elements exert their
      effects by influencing diverse processes, such as RNA editing, exonization, and
      RNA processing. In so doing, they have undoubtedly had a profound effect on human
      evolution.

PMID- 26223269
TI  - The ecdysone receptor signalling regulates microvilli formation in follicular
      epithelial cells.
AB  - Epithelial morphogenesis contributes greatly to the development and homeostasis
      of the organs and body parts. Here, we analysed the consequences of impaired
      ecdysone receptor (EcR) signalling in the Drosophila follicular epithelium.
      Besides governing cell growth, the three EcR isoforms act redundantly in
      controlling follicle cell positioning. Flattening of the microvilli and an
      aberrant actin cytoskeleton arise from defective EcR signalling in follicle
      cells, and these defects impact on the organisation of the oocyte membrane. We
      found that this signalling governs a complex molecular network since its
      impairment affects key molecules as atypical protein kinase C and activated
      Moesin. Interestingly, the activity of the transcription factor Tramtrack69
      isoform is required for microvilli and their actin core morphogenesis as well as
      for follicle cell positioning. In conclusion, our findings provide evidence of
      novel roles for EcR signalling and Tramtrack69 transcription factor in
      controlling stage-specific differentiation events that take place in the
      follicular epithelium. 

PMID- 26223272
TI  - Erratum.

PMID- 26223271
TI  - Regional hyperthermia of the abdomen, a pilot study towards the treatment of
      peritoneal carcinomatosis.
AB  - BACKGROUND: Peritoneal carcinomatosis occurs in different cancer subtypes and is
      associated with a dismal prognosis. Some doubts remain whether the whole abdomen
      can be treated by regional hyperthermia, therefore we analyzed feasibility
      conducting a pilot study. METHODS: A simulation of the abdominopelvic heat
      distribution in 11 patients with peritoneal carcinomatosis was done using the
      HyperPlan software and the SIGMA-60 and SIGMA-Eye applicators. Tissue-specific
      region-related electrical and thermal parameters were used to solve the Maxwell's
      equations and the bioheat-transfer equation. Three-dimensional specific
      absorption rate (SAR) distributions and, additionally, estimated region-related
      perfusion rates were used to solve the bioheat-transfer equation. The predicted
      SAR and temperature distributions were compared with minimally invasive
      measurements in pelvic reference points. RESULTS: In 11 patients (7 of them
      treated in the SIGMA-60 and 4 in the SIGMA-Eye applicator) the measured treatment
      variables (SAR, temperatures in the pelvic reference points) indicated that the
      heated volumes were higher for the SIGMA-Eye applicator. The mean computed
      abdominal SARs were less for the SIGMA-Eye (33 versus 44 W/kg). Nevertheless, the
      temperature distributions in the abdomen (peritoneal cavity) were more
      homogeneous in the SIGMA-Eye applicator as compared to the SIGMA-60 as indicated
      by higher values of T90 (mean 40.2 versus 38.2  degrees C) and T50 (mean 41.1
      versus 40.2  degrees C), while the maximum temperatures were similar (in the
      range 41 to 43  degrees C). Even though the mean abdominal SAR was lower in the
      SIGMA-Eye, the heat distribution covered a larger volume of the abdomen (in
      particular the upper abdomen). For the SIGMA-60 applicator the achieved T90
      appeared to be limited between 41 and 42  degrees C, for the SIGMA Eye applicator
      more effective T90 in the range 42 to 43  degrees C were obtained. CONCLUSION:
      Our results suggest that an adequate heating of the abdomen and therefore
      abdominal regional hyperthermia in PC patients appears feasible. The SIGMA-Eye
      applicator appears to be superior compared to the SIGMA-60 applicator for
      abdominal hyperthermia.

PMID- 26223273
TI  - Lack of the scavenger receptor CD36 alters microglial phenotypes after neonatal
      stroke.
AB  - The stage of brain development at the time of stroke has a major impact on the
      pathophysiological mechanisms of ischemic damage, including the neuroinflammatory
      response. Microglial cells have been shown to contribute to acute and subchronic
      injury in adult stroke models, whereas in neonatal rodents we showed that
      microglial cells serve as endogenous neuroprotectants early following transient
      middle cerebral artery occlusion, limiting neuroinflammation and injury. In the
      neonate, microglial depletion or lack of the scavenger receptor CD36 exacerbates
      injury. In this study we asked if lack of CD36 affects microglial phenotypes
      after neonatal stroke. Using RT-PCR we characterized the patterns of gene
      expression in microglia isolated from injured regions following acute transient
      middle cerebral artery occlusion in postnatal day 10 mice and showed that
      expression of several pro-inflammatory genes, including Toll-like receptors,
      remains largely unaffected in activated microglia in injured regions. Using
      multiple biochemical assays we demonstrated that lack of CD36 alters several
      functions of microglia in acutely injured neonatal brain: it further enhances
      accumulation of the chemokine MCP-1, affects the number of CD11b(+) /CD45(+)
      cells, along with protein expression of its co-receptor, Toll-like receptor 2,
      but does not affect accumulation of superoxide in microglia or the cytokines
      TNFalpha and IL-1beta in injured regions.

PMID- 26223274
TI  - Assessing the cost of contemporary pituitary care.
AB  - OBJECT: Knowledge of the costs incurred through the delivery of neurosurgical
      care has been lagging, making it challenging to design impactful cost-containment
      initiatives. In this report, the authors describe a detailed cost analysis for
      pituitary surgery episodes of care and demonstrate the importance of such
      analyses in helping to identify high-impact cost activities and drive value-based
      care. METHODS: This was a retrospective study of consecutively treated patients
      undergoing an endoscopic endonasal procedure for the resection of a pituitary
      adenoma after implementation and maturation of quality-improvement initiatives
      and the implementation of cost-containment initiatives. RESULTS: The cost data
      pertaining to 27 patients were reviewed. The 2 most expensive cost activities
      during the index hospitalization were the total operating room (OR) and total bed
      assignment costs. Together, these activities represented more than 60% of the
      cost of hospitalization. Although value-improvement initiatives contributed to
      the reduction of variation in the total cost of hospitalization, specific cost
      activities remained relatively variable, namely the following: 1) OR charged
      supplies, 2) postoperative imaging, and 3) use of intraoperative neuromonitoring.
      These activities, however, each contributed to less than 10% of the cost of
      hospitalization. Bed assignment was the fourth most variable cost activity. Cost
      related to readmission/reoperation represented less than 5% of the total cost of
      the surgical episode of care. CONCLUSIONS: After completing a detailed assessment
      of costs incurred throughout the management of patients undergoing pituitary
      surgery, high-yield opportunities for cost containment should be identified among
      the most expensive activities and/or those with the highest variation. Strategies
      for safely reducing the use of the targeted resources, and related costs
      incurred, should be developed by the multidisciplinary team providing care for
      this patient population.

PMID- 26223275
TI  - A scoping review of biomechanical testing for proximal humerus fracture implants.
AB  - BACKGROUND: Fixation failure is a relatively common sequela of surgical
      management of proximal humerus fractures (PHF). The purpose of this study is to
      understand the current state of the literature with regard to the biomechanical
      testing of proximal humerus fracture implants. METHODS: A scoping review of the
      proximal humerus fracture literature was performed, and studies testing the
      mechanical properties of a PHF treatment were included in this review.
      Descriptive statistics were used to summarize the characteristics and methods of
      the included studies. RESULTS: 1,051 proximal humerus fracture studies were
      reviewed; 67 studies met our inclusion criteria. The most common specimen used
      was cadaver bone (87%), followed by sawbones (7%) and animal bones (4%). A two
      part fracture pattern was tested most frequently (68%), followed by three-part
      (23%), and four-part (8%). Implants tested included locking plates (52%),
      intramedullary devices (25%), and non-locking plates (25%). Hemi-arthroplasty was
      tested in 5 studies (7%), with no studies using reverse total shoulder
      arthroplasty (RTSA) implants. Torque was the most common mode of force applied
      (51%), followed by axial loading (45%), and cantilever bending (34%). Substantial
      testing diversity was observed across all studies. CONCLUSIONS: The biomechanical
      literature was found to be both diverse and heterogeneous. More complex fracture
      patterns and RTSA implants have not been adequately tested. These gaps in the
      current literature will need to be addressed to ensure that future biomechanical
      research is clinically relevant and capable of improving the outcomes of
      challenging proximal humerus fracture patterns.

PMID- 26223276
TI  - MMP1 gene expression enhances myoblast migration and engraftment following
      implanting into mdx/SCID mice.
AB  - Myoblast transplantation (MT) is a method to introduce healthy genes into
      abnormal skeletal muscle. It has been considered as a therapeutic modality in the
      last few decades for diseases such as Duchenne Muscular Dystrophy (DMD). However,
      challenges including cell death and poor graft engraftment have limited its
      application. The current experiment utilizes MMP1 gene transfer to improve the
      efficacy of myoblast transplantation into the diseased dystrophic skeletal muscle
      of mdx mice. Our results indicated that MMP1 expression can promote myogenic
      differentiation and fusion capacities, increase migration of MMP1 expressing
      myoblasts in vitro, as well as improve engraftment of dystrophin positive
      myofibers in vivo. Taken together, our observation suggests that the addition of
      MMP1 can overcome limitations in MT and improve its clinical efficacy. 

PMID- 26223281
TI  - Competing infant feeding information in mothers' networks: advice that supports
      v. undermines clinical recommendations.
AB  - OBJECTIVE: To identify the social contextual factors, specifically the presence
      of information that supports v. undermines clinical recommendations, associated
      with infant feeding behaviours among mothers in low-income areas. DESIGN: Cross
      sectional survey evaluating social support networks and social relationships
      involved in providing care to the infant along with feeding beliefs and
      practices. SETTING: Out-patient paediatric and government-funded (Women, Infants,
      and Children) clinics in an urban, low-income area of the south-eastern USA.
      SUBJECTS: Eighty-one low-income mothers of infants between 0 and 12 months old.
      RESULTS: Most mothers reported receiving both supportive and undermining advice.
      The presence of breast-feeding advice that supports clinical recommendations was
      associated with two infant feeding practices that are considered beneficial to
      infant health: ever breast-feeding (OR=6.7; 95% CI 1.2, 38.1) and not adding
      cereal in the infant's bottle (OR=15.9; 95% CI 1.1, 227.4). Advice that
      undermines clinical recommendations to breast-feed and advice about solid foods
      were not associated with these behaviours. CONCLUSIONS: Efforts to facilitate
      optimal infant feeding practices may focus on increasing information supportive
      of clinical recommendations while concentrating less on reducing the presence of
      undermining information within mothers' networks. Cultural norms around breast
      feeding may be stronger than the cultural norms around the introduction of solid
      foods in mothers' social environments; thus, additional efforts to increase
      information regarding introduction of solid foods earlier in mothers' infant care
      career may be beneficial.

PMID- 26223282
TI  - Impact of delays in initiating postoperative chemoradiation while determining the
      MGMT promoter-methylation statuses of patients with primary glioblastoma.
AB  - BACKGROUND: The benefits of new innovations in glioblastoma therapies should not
      be curtailed as a result of delays in commencement of radiation therapy, caused
      by clinical circumstances as well as diagnostic procedures. This study evaluates
      whether delays in chemo-radiotherapy after surgery, while determining O6
      methylguanine-DNA-methyltransferase (MGMT) promoter status, affect the survival
      rates of patients with glioblastoma (GBM). METHODS: Our sample comprised 50 GBM
      patients in a retrospective analysis of three prospective studies that focused on
      combined radiotherapy and required MGMT promoter-status testing as inclusion
      criteria. Results were compared with a reference group of 127 favourable GBM
      cases (Karnofsky performance-status scale >= 70), in which the patients underwent
      standard postoperative chemo-radiotherapy with temozolomide. Survival time was
      calculated using the Kaplan-Meier method, and a multivariate analysis of the
      delays between surgical and radiotherapy procedures was performed using the Cox
      regression model. RESULTS: The study group's median overall survival time was
      16.2 months (with a range of 2 to 56 months), versus the reference group's
      survival time of 18.2 months (with a range of 1 to 92 months) (p = 0.64). The
      delay between surgery and radiotherapy was increased by 8 days in the study
      patients (p < 0.001), with a median delay of 35 days (range: 18-49 days)
      corresponding to the typical 27-day delay (range: 5-98 days) for those in the
      reference group. Univariate and multivariate analyses did not show any negative
      association between survival time and delaying radiation therapy to determine
      MGMT-promoter status; commencement of radiation therapy sooner than 24 days after
      surgery was the threshold for significantly decreased overall survival (p = 0.01)
      and progression-free (p = 0.03) survival. CONCLUSION: Delaying postoperative
      chemoradiation for GBM patients--carried out in order to determine MGMT-promoter
      status-did not have a negative impact on survival time. Indeed, the data of the
      present study shows that initiating radiation therapy sooner than 24 days after
      surgery has a negative impact on progression and survival.

PMID- 26223283
TI  - Gallic acid protects against cyclophosphamide-induced toxicity in testis and
      epididymis of rats.
AB  - The protective role of gallic acid (GA) on reproductive toxicity induced by
      cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar
      rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received
      distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg(-1)
      for 14 consecutive days, respectively. Group 4 received a single intraperitoneal
      dose of CPA at 200 mg kg(-1) on day 1. Groups 5 and 6 received a single dose of
      CPA (200 mg kg(-1) ) intraperitoneally on day 1 followed by treatment with GA at
      60 and 120 mg kg(-1) for 14 consecutive days, respectively. In testes and
      epididymis of the treated rats, CPA administration resulted in significant
      elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide
      levels. There was a significant decrease in the activities of superoxide
      dismutase and glutathione-S-transferase. Furthermore, there were significant
      reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH)
      and testosterone levels, which were accompanied by significant decrease in sperm
      motility and viability in CPA-treated rats. Histological examination revealed
      marked testicular and epididymal atrophy in CPA alone treated rats and these
      aberrations were reversed by GA. In conclusion, GA has capacity to protect
      against reproductive toxicity induced by cyclophosphamide.

PMID- 26223285
TI  - Preparation of hybrid monolithic columns via "one-pot" photoinitiated thiol
      acrylate polymerization for retention-independent performance in capillary liquid
      chromatography.
AB  - A novel "one-pot" approach was developed for ultrarapid preparation of various
      hybrid monolithic columns in UV-transparent fused-silica capillaries via
      photoinitiated thiol-acrylate polymerization of an acrylopropyl polyhedral
      oligomertic silsesquioxane (acryl-POSS) and a monothiol monomer (1
      octadecanethiol or sodium 3-mercapto-1-propanesulfonate) within 5 min, in which
      the acrylate not only homopolymerizes, but also couples with the thiol. This
      unique combination of two types of free-radical reaction mechanisms offers a
      simple way to fabricate various acrylate-based hybrid monoliths. The physical
      characterization, including scanning electron microscopy (SEM), Fourier transform
      infrared (FT-IR) spectroscopy, and thermal gravimetric analysis was performed.
      The results indicated that the monothiol monomers were successfully incorporated
      into acryl-POSS-based hybrid monoliths. The column efficiencies for alkylbenzenes
      on the C18-functionalized hybrid monolithic column reached to 60 000-73 500
      plates/m at the velocity of 0.33 mm/s in capillary liquid chromatography, which
      was far higher than that of previously reported POSS-based columns prepared via
      thermal-initiated free-radical polymerization without adding any thiol monomers.
      By plotting the plate height (H) of the alkylbenzenes versus the linear velocity
      (u) of the mobile phase, the results revealed a retention-independent efficient
      performance of small molecules in the isocratic elution. These results indicated
      that more homogeneous hybrid monoliths formed via photoinitiated thiol-acrylate
      polymerization; particularly, the use of the multifunctional cross-linker
      possibly prevented the generation of gel-like micropores, reducing mass transfer
      resistance (C-term). Another sulfonate-containing hybrid monolithic column also
      exhibited hydrophobicity and ion-exchange mechanism, and the dynamic binding
      capacity was calculated as 71.1 ng/cm (75 MUm i.d.). 

PMID- 26223284
TI  - A postpartum haemorrhage package with condom uterine balloon tamponade: a
      prospective multi-centre case series in Kenya, Sierra Leone, Senegal, and Nepal.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of an ultra-low-cost uterine
      balloon tamponade package (ESM-UBTTM) for facility-based management of
      uncontrolled postpartum haemorrhage (PPH) in Kenya, Sierra Leone, Senegal, and
      Nepal. DESIGN: Prospective multi-centre case series. SETTING: Facilities in
      resource-scarce areas of Kenya, Sierra Leone, Nepal, and Senegal. POPULATION:
      Women with uncontrolled postpartum haemorrhage in 307 facilities across the four
      countries. METHODS: A standardised ESM-UBT package was implemented in 307
      facilities over 29 months (1 September 2012 to 1 February 2015). Data were
      collected via a multi-pronged approach including data card completion, chart
      reviews, and provider interviews. Beginning in August 2014, women who had
      previously undergone UBT placement were sought and queried regarding potential
      complications associated with UBT use. MAIN OUTCOME MEASURES: All-cause survival,
      survival from PPH, and post-UBT use complications (surgery, hospitalisation,
      antibiotics for pelvic infection) associated with UBT use. RESULTS: 201 UBTs were
      placed for uncontrolled vaginal haemorrhage refractory to all other
      interventions. In all, 38% (71/188) of women were either unconscious or confused
      at the time of UBT insertion. All-cause survival was 95% (190/201). However, 98%
      (160/163) of women survived uncontrolled PPH if delivery occurred at an ESM-UBT
      online facility. One (1/151) potential UBT-associated complication (postpartum
      endometritis) was identified and two improvised UBTs were placed in women with a
      ruptured uterus. CONCLUSIONS: These pilot data suggest that the ESM-UBT package
      is a clinically promising and safe method to arrest uncontrolled postpartum
      haemorrhage and save women's lives. The UBT was successfully placed by all levels
      of facility-based providers. Future studies are needed to further evaluate the
      effectiveness of ESM-UBT in low-resource settings. TWEETABLE ABSTRACT: Evidence
      for ESM-UBT as a clinically promising and safe method to arrest uncontrolled PPH
      and save women's lives.

PMID- 26223286
TI  - Octreotide protects ovary against ischemia-reperfusion injury in rats: Evaluation
      of histological and biochemical parameters.
AB  - AIM: This study investigated the efficacy of octreotide for prevention of
      ischemia-reperfusion injury in rat ovary. METHODS: Thirty-two adult female rats
      were included. Rats were divided into five groups: in the sham group, the
      abdominal wall was only opened and closed; in the torsion group, ischemia was
      induced for 3 h using a torsion model involving atraumatic vascular clips; in the
      torsion/octreotide group, rats were given 100 ug/kg i.p. octreotide 30 min before
      torsion was induced; in the torsion/detorsion group, rats underwent 3 h ischemia
      3 h reperfusion; in the torsion/detorsion/octreotide group, rats underwent 3 h
      ischemia followed by 100 ug/kg octreotide i.p. 30 min prior to 3 h reperfusion.
      Ovarian tissue damage was scored on histopathology. Ovarian tissue
      malondialdehyde and plasma pentraxin 3 were measured biochemically. RESULTS: In
      comparison with the sham group, both the torsion and torsion/detorsion groups had
      significantly higher scores for follicular degeneration, vascular congestion,
      edema, hemorrhage and leukocyte infiltration. Octreotide significantly decreased
      these scores in both groups. Ovarian malondialdehyde and plasma pentraxin 3 were
      significantly higher both in the torsion and torsion/detorsion groups compared
      with the sham group. Octreotide also decreased these levels significantly both in
      the torsion/octreotide and torsion/detorsion/octreotide groups. CONCLUSION:
      Octreotide ameliorated the potential side-effects of ovarian ischemia-reperfusion
      injury in a rat model.

PMID- 26223287
TI  - Cytochrome P450 2C19 polymorphisms and valproic acid-induced weight gain.
AB  - OBJECTIVES: Cytochrome P450 (CYP) 2C19 plays a role in the biotransformation of
      clinically relevant drugs as well as endogenous compounds, including sex
      hormones, which are known to be modulators of food intake and energy balance in
      humans. We attempted to investigate the influence of CYP2C19 polymorphisms on
      valproic acid (VPA)-induced weight gain. MATERIALS AND METHODS: This
      retrospective longitudinal study included 85 VPA-treated and 93 carbamazepine
      (CBZ)-treated (as a reference) young patients with epilepsy. The body mass index
      (BMI) gap between the patient's BMI and the cutoff value for being overweight was
      calculated in each patient during the follow-up period. The longitudinal
      associations of the CYP2C19 genotype with the BMI gap and risk for becoming
      overweight during VPA or CBZ therapy were examined retrospectively using the
      generalized estimating equations approach and the Kaplan-Meier method. RESULTS:
      During the follow-up period, the values of the BMI gap were significantly greater
      (P = 0.002 or P = 0.005) and the cumulative incidence of becoming overweight
      tended to be higher (P = 0.032) in the VPA-treated female patients with one or
      two loss-of-function CYP2C19 alleles than in the females without the loss-of
      function CYP2C19 alleles. No associations were observed among the VPA-treated
      male patients and CBZ-treated male and female patients (P > 0.05). CONCLUSIONS:
      This is the first report to show a relationship between the CYP2C19 polymorphism
      and VPA-induced weight gain in female patients with epilepsy. Further
      investigations are needed to verify these findings.

PMID- 26223288
TI  - Similar outcome of upfront-unrelated and matched sibling stem cell
      transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of
      the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe
      Aplastic Anaemia Working Party of EBMT.
AB  - We explored the feasibility of unrelated donor haematopoietic stem cell
      transplant (HSCT) upfront without prior immunosuppressive therapy (IST) in
      paediatric idiopathic severe aplastic anaemia (SAA). This cohort was then
      compared to matched historical controls who had undergone first-line therapy with
      a matched sibling/family donor (MSD) HSCT (n = 87) or IST with horse
      antithymocyte globulin and ciclosporin (n = 58) or second-line therapy with
      unrelated donor HSCT post-failed IST (n = 24). The 2-year overall survival in the
      upfront cohort was 96 +/- 4% compared to 91 +/- 3% in the MSD controls (P = 0.30)
      and 94 +/- 3% in the IST controls (P = 0.68) and 74 +/- 9% in the unrelated donor
      HSCT post-IST failure controls (P = 0.02).The 2-year event-free survival in the
      upfront cohort was 92 +/- 5% compared to 87 +/- 4% in MSD controls (P = 0.37), 40
      +/- 7% in IST controls (P = 0.0001) and 74 +/- 9% in the unrelated donor HSCT
      post-IST failure controls (n = 24) (P = 0.02). Outcomes for upfront-unrelated
      donor HSCT in paediatric idiopathic SAA were similar to MSD HSCT and superior to
      IST and unrelated donor HSCT post-IST failure. Front-line therapy with matched
      unrelated donor HSCT is a novel treatment approach and could be considered as
      first-line therapy in selected paediatric patients who lack a MSD. 

PMID- 26223289
TI  - Substance P in the anterior thalamic paraventricular nucleus: promotion of
      ethanol drinking in response to orexin from the hypothalamus.
AB  - The paraventricular nucleus of the thalamus (PVT) appears to participate in drug
      addiction. Recent evidence in rats shows that ethanol drinking is increased by
      orexin/hypocretin (OX) afferents from the hypothalamus, acting specifically in
      the anterior (aPVT) rather than posterior (pPVT) PVT subregion. The present study
      sought to identify neuropeptides transcribed within the PVT, which themselves
      might contribute to ethanol drinking and possibly mediate the actions of OX. We
      discovered that substance P (SP) in the aPVT can stimulate intermittent-access
      ethanol drinking, similar to OX, and that SP receptor [neurokinin 1
      receptor/tachykinin receptor 1 (NK1R)] antagonists in this subregion reduce
      ethanol drinking. As with OX, this effect is site specific, with SP in the pPVT
      or dorsal third ventricle having no effect on ethanol drinking, and it is
      behaviorally specific, with SP in the aPVT reducing the drinking of sucrose and
      stimulating it in the pPVT. A close relationship between SP and OX was
      demonstrated by a stimulatory effect of local OX injection on SP mRNA and peptide
      levels, specifically in the aPVT but not pPVT, and a stimulatory effect of OX on
      SP expression in isolated thalamic neurons, reflecting postsynaptic actions. A
      functional relationship between OX and SP in the aPVT is suggested by our
      additional finding that ethanol drinking induced by OX is blocked by a local NK1R
      antagonist administered at a sub-threshold dose. These results, suggesting that
      SP in the aPVT mediates the stimulatory effect of OX on ethanol drinking,
      identify a new role for SP in the control of this behavior.

PMID- 26223290
TI  - Biocompatibility of a titanium dioxide-coating method for denture base acrylic
      resin.
AB  - OBJECTIVES: Ease of denture cleaning is of paramount importance in geriatric
      patients and those with limited dexterity. We have previously investigated
      methods of coating dentures with titanium dioxide (TiO2 ) and reported the
      effects (self-cleaning and antibacterial) of such treatments in in vitro studies.
      This study was to verify the biocompatibility of a TiO2 -coated acrylic resin
      produced by the new coating method with spray-coating technique. METHODS:
      Specimens were prepared from denture base acrylic resin and polished up to grit
      #1000. The TiO2 -coating agent was sprayed onto the specimens using an airbrush
      gun. Specimens were then divided into 'polymethyl methacrylate (PMMA)', 'primer
      coated PMMA' and 'TiO2 -coated PMMA' groups to be evaluated for biological safety
      using a hamster oral mucosa irritation test, a guinea pig skin sensitisation test
      and a rabbit intracutaneous test. The biological reaction was scored. RESULTS:
      Reaction scores were considerably <1.0, the acceptable limit set by the ISO, in
      all three tests. Indeed, in most samples, there was no deleterious effect at all.
      CONCLUSION: These results tested on animals demonstrate that denture base resin
      coated with TiO2 by this method does not cause irritation or sensitisation of the
      oral mucosa, skin or intracutaneous tissue and is therefore good biocompatibility
      for use in close proximity to oral mucosa and skin.

PMID- 26223291
TI  - Teasing apart the anticipatory and consummatory processing of monetary
      incentives: An event-related potential study of reward dynamics.
AB  - The monetary incentive delay (MID) task has been widely used in fMRI studies to
      investigate the neural networks involved in anticipatory and consummatory reward
      processing. Previous efforts to adapt the MID task for use with ERPs, however,
      have had limited success. Here, we sought to further decompose reward dynamics
      using a comprehensive set of anticipatory (cue-N2, cue-P3, contingent negative
      variation [CNV]) and consummatory ERPs (feedback negativity [FN], feedback P3 [fb
      P3]). ERP data was recorded during adapted versions of the MID task across two
      experiments. Unlike previous studies, monetary incentive cues modulated the cue
      N2, cue-P3, and CNV; however, cue-related ERPs and the CNV were uncorrelated with
      one another, indicating distinct anticipatory subprocesses. With regard to
      consummatory processing, FN amplitude primarily tracked outcome valence (reward
      vs. nonreward), whereas fb-P3 amplitude primarily tracked outcome salience
      (uncertain vs. certain). Independent modulation of the cue-P3 and fb-P3 was
      observed, indicating that these two P3 responses may uniquely capture the
      allocation of attention during anticipatory and consummatory reward processing,
      respectively. Overall, across two samples, consistent evidence of both
      anticipatory and consummatory ERP activity was observed on an adapted version of
      the MID paradigm, demonstrating for the first time how these ERP components may
      be integrated with one another to more fully characterize the time course of
      reward processing. This ERP-MID paradigm is well suited to parsing reward
      dynamics, and can be applied to both healthy and clinical populations. 

PMID- 26223292
TI  - Quantification of Amino Groups on Solid Surfaces Using Cleavable Fluorescent
      Compounds.
AB  - We quantified amino groups displayed on inorganic and organic surfaces in aqueous
      solution using different types of cleavable fluorescent compounds and an aldehyde
      dye. The cleavable fluorescent compounds were designed to bind covalently to
      amino groups and then liberated under specific conditions. Among the investigated
      materials, cleavable coumarin was most appropriate for the quantification of
      amino groups on silica and resin surfaces. The developed method can measure small
      amounts (~pmol/cm(2)) of amino groups on a flat polymeric surface, detecting only
      amino groups that are exposed to aqueous solution and available for surface
      immobilization of ligands and biomolecules. 

PMID- 26223293
TI  - Biomimetic peptide-based models of [FeFe]-hydrogenases: utilization of phosphine
      containing peptides.
AB  - Two synthetic strategies for incorporating diiron analogues of [FeFe]
      hydrogenases into short peptides via phosphine functional groups are described.
      First, utilizing the amine side chain of lysine as an anchor, phosphine
      carboxylic acids can be coupled via amide formation to resin-bound peptides.
      Second, artificial, phosphine-containing amino acids can be directly incorporated
      into peptides via solution phase peptide synthesis. The second approach is
      demonstrated using three amino acids each with a different phosphine substituent
      (diphenyl, diisopropyl, and diethyl phosphine). In total, five distinct
      monophosphine-substituted, diiron model complexes were prepared by reaction of
      the phosphine-peptides with diiron hexacarbonyl precursors, either (MU
      pdt)Fe2(CO)6 or (MU-bdt)Fe2(CO)6 (pdt = propane-1,3-dithiolate, bdt = benzene-1,2
      dithiolate). Formation of the complexes was confirmed by UV/Vis, FTIR and (31)P
      NMR spectroscopy. Electrocatalysis by these complexes is reported in the presence
      of acetic acid in mixed aqueous-organic solutions. Addition of water results in
      enhancement of the catalytic rates. 

PMID- 26223294
TI  - Lupus in a patient with cystinosis: is it drug induced?
AB  - A 9-year-old girl with a diagnosis of cystinosis since 2 years of age, on
      cysteamine therapy, presented with complaints of serositis and arthritis, and
      laboratory tests revealed high antinuclear antibody titers with
      hypocomplementemia. Kidney biopsy was not consistent with lupus nephritis. With
      prednisolone treatment her complaints resolved and creatinine level decreased,
      but on follow-up, serological features of systemic lupus erythematosus (SLE)
      continued. Six years after cessation of prednisolone, lupus features were
      reactivated, with positive antihistone antibodies and ANCA. Coincidence of
      cystinosis and SLE is very rare, and to the best of our knowledge this is the
      fourth case reported in the literature. Physicians should be aware that
      cystinosis patients may have some autoimmune manifestations with features of true
      or drug-induced lupus. In the light of this case, pathophysiology and treatment
      are discussed. 

PMID- 26223295
TI  - Elevated expressions of myeloid-related proteins-8 and -14 are danger biomarkers
      for lupus nephritis.
AB  - Myeloid-related proteins, MRP-8 and -14, which have been identified as molecules
      that mediate the danger signaling in innate immune response, are also known as
      the DAMPs (damage associated molecular pattern molecules). The proteins were
      found in infiltrating macrophages and neutrophils at inflammatory sites. Their
      expression was correlated with severe forms of glomerulonephritis. Therefore,
      this study examined whether or not MRP-8 and -14 can be used as biomarkers for
      identifying severely active lupus nephritis (LN). Total blood leukocyte samples
      and renal biopsy tissues from a prospective cohort of LN patients were used to
      determine mRNA and protein expression levels of MRP-8 and -14. The mRNA levels of
      MRP-8 and -14 in total blood leukocytes were significantly higher in active LN
      patients than quiescent LN patients and healthy controls. Moreover, the mRNA
      levels of MRP-8 and -14 in the total blood leukocytes and kidney tissues were
      significantly correlated with therapeutic response and the mRNA expression levels
      in the kidney were associated with an early loss of the kidney function. MRP-8
      and -14 can be used as non-invasive prognostic biomarkers in patients with LN. 

PMID- 26223296
TI  - Assessment of anti-Mullerian hormone levels in premenopausal patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: The ovarian reserve of patients with systemic lupus erythematosus
      (SLE) may be affected by disease activity and medication use. Studies have found
      that patients with SLE have similar fertility rates as healthy women of the same
      age. The goal of the present study was to investigate the ovarian reserve of
      patients with SLE by measuring anti-Mullerian hormone (AMH) levels, and compare
      it to that of healthy controls. METHOD: This was a case-control study performed
      on 80 premenopausal women, of whom 40 fulfilled the 1997 American College of
      Rheumatology (ACR) criteria for SLE and 40 healthy controls paired by oral
      contraceptive use. Serum concentrations of AMH in peripheral venous blood were
      measured using a human AMH ELISA kit (CUSABIO, Wuhan, China). RESULTS: AMH serum
      levels did not differ between patients with SLE and controls (22.79 +/- 17.32
      ng/ml versus 21.41 +/- 16.22 ng/ml, respectively, p = 0.7), even after adjusting
      for age (21.03 +/- 2.074 ng/ml versus 23.97 +/- 2.71 ng/ml; p = 0.5). AHM levels
      were not significantly correlated with disease duration (r = 0.2; p = 0.3), body
      mass index (r = 0.2; p = 0.2) and disease activity (SLEDAI (r = 0.1; p = 0.7))
      and damage indices (SLICC (r = 0.1; p = 0.7)). No associations were found between
      AMH and ethnicity, current smoking, as well as current or prior use of
      cyclophosphamide and other immunosuppressants. CONCLUSION: In this cross
      sectional study, women with SLE demonstrated similar AMH levels as healthy
      controls, suggesting preserved ovarian reserve in this population.

PMID- 26223297
TI  - Juvenile systemic lupus erythematosus: onset patterns and short-term outcome in
      Egyptian children, a single-center experience.
AB  - OBJECTIVE: The objective of this article is to define disease onset pattern and
      understand the response to therapy in children with systemic lupus erythematosus
      (SLE) in Egypt. METHODS: A prospective cohort of 41 Egyptian children diagnosed
      with SLE was analyzed. SLE Disease Activity Index (SLEDAI) score was used to
      record disease activity at onset, and renal biopsy was performed to define the
      stage of lupus nephritis. Response to therapy over a follow-up period ranging
      from 10 to 50 months was evaluated. RESULTS: The mean age at diagnosis was 12.12
      +/- 3.45 years. Thirty-six (87.8%) patients were females. Most patients had
      multiple manifestations at onset. The most common presenting symptoms were pallor
      and fever (51.2% and 43.9%, respectively). Lupus nephritis was found in 27
      (65.9%) children. International Society of Nephrology (ISN) classes I and III
      were the most common findings on renal biopsy. Neuropsychiatric manifestations
      were present at disease onset in 19 patients (46.3%) with a bad prognostic
      course. At diagnosis, high SLEDAI scores were recorded (mean: 29.95 +/- 2.06).
      The mean renal SLEDAI score was 10.2 +/- 4. At follow-up 16 (39.02%) patients
      were in complete remission, 10 (24.39%) were in partial remission, two (4.87%)
      had active disease, five (12.9%) had relapsed, four (9.75%) had died and four
      (9.75%) patients were lost to follow-up. CONCLUSIONS: Egyptian children with SLE
      appear to have severe disease on presentation with high SLEDAI scores and high
      prevalence of lupus nephritis, but respond well to therapy with a favorable short
      term prognosis.

PMID- 26223298
TI  - Drug-induced hearing loss: Infection raises the odds.
AB  - Inflammation due to bacterial infection exacerbates hearing loss caused by
      aminoglycoside antibiotic treatment in a mouse model of sepsis (Koo et al.). 

PMID- 26223299
TI  - Clinical research: Should patients pay to play?
AB  - Permitting patients to pay for participation in clinical research threatens the
      principles of social value and fair subject selection as well as robust clinical
      trial design. 

PMID- 26223300
TI  - Cancer chemoprevention: Evidence of a nonlinear dose response for the protective
      effects of resveratrol in humans and mice.
AB  - Resveratrol is widely promoted as a potential cancer chemopreventive agent, but a
      lack of information on the optimal dose prohibits rationally designed trials to
      assess efficacy. To challenge the assumption that "more is better," we compared
      the pharmacokinetics and activity of a dietary dose with an intake 200 times
      higher. The dose-response relationship for concentrations generated and the
      metabolite profile of [(14)C]-resveratrol in colorectal tissue of cancer patients
      helped us to define clinically achievable levels. In Apc(Min) mice (a model of
      colorectal carcinogenesis) that received a high-fat diet, the low resveratrol
      dose suppressed intestinal adenoma development more potently than did the higher
      dose. Efficacy correlated with activation of adenosine monophosphate-activated
      protein kinase (AMPK) and increased expression of the senescence marker p21.
      Nonlinear dose responses were observed for AMPK and mechanistic target of
      rapamycin (mTOR) signaling in mouse adenoma cells, culminating in autophagy and
      senescence. In human colorectal tissues exposed to low dietary concentrations of
      resveratrol ex vivo, we measured enhanced AMPK phosphorylation and autophagy. The
      expression of the cytoprotective NAD(P)H dehydrogenase, quinone 1 (NQO1) enzyme
      was also increased in tissues from cancer patients participating in our [(14)C]
      resveratrol trial. These findings warrant a revision of developmental strategies
      for diet-derived agents designed to achieve cancer chemoprevention. 

PMID- 26223302
TI  - Tyrosine kinase inhibitor-induced CD70 expression mediates drug resistance in
      leukemia stem cells by activating Wnt signaling.
AB  - In chronic myelogenous leukemia (CML), oncogenic BCR-ABL1 activates the Wnt
      pathway, which is fundamental for leukemia stem cell (LSC) maintenance. Tyrosine
      kinase inhibitor (TKI) treatment reduces Wnt signaling in LSCs and often results
      in molecular remission of CML; however, LSCs persist long term despite BCR-ABL1
      inhibition, ultimately causing disease relapse. We demonstrate that TKIs induce
      the expression of the tumor necrosis factor (TNF) family ligand CD70 in LSCs by
      down-regulating microRNA-29, resulting in reduced CD70 promoter DNA methylation
      and up-regulation of the transcription factor specificity protein 1. The
      resulting increase in CD70 triggered CD27 signaling and compensatory Wnt pathway
      activation. Combining TKIs with CD70 blockade effectively eliminated human
      CD34(+) CML stem/progenitor cells in xenografts and LSCs in a murine CML model.
      Therefore, targeting TKI-induced expression of CD70 and compensatory Wnt
      signaling resulting from the CD70/CD27 interaction is a promising approach to
      overcoming treatment resistance in CML LSCs. 

PMID- 26223301
TI  - Endotoxemia-mediated inflammation potentiates aminoglycoside-induced ototoxicity.
AB  - The ototoxic aminoglycoside antibiotics are essential to treat severe bacterial
      infections, particularly in neonatal intensive care units. Using a bacterial
      lipopolysaccharide (LPS) experimental model of sepsis, we tested whether LPS
      mediated inflammation potentiates cochlear uptake of aminoglycosides and
      permanent hearing loss in mice. Using confocal microscopy and enzyme-linked
      immunosorbent assays, we found that low-dose LPS (endotoxemia) greatly increased
      cochlear concentrations of aminoglycosides and resulted in vasodilation of
      cochlear capillaries without inducing paracellular flux across the blood
      labyrinth barrier (BLB) or elevating serum concentrations of the drug.
      Additionally, endotoxemia increased expression of both serum and cochlear
      inflammatory markers. These LPS-induced changes, classically mediated by Toll
      like receptor 4 (TLR4), were attenuated in TLR4-hyporesponsive mice. Multiday
      dosing with aminoglycosides during chronic endotoxemia induced greater hearing
      threshold shifts and sensory cell loss compared to mice without endotoxemia.
      Thus, endotoxemia-mediated inflammation enhanced aminoglycoside trafficking
      across the BLB and potentiated aminoglycoside-induced ototoxicity. These data
      indicate that patients with severe infections are at greater risk of
      aminoglycoside-induced hearing loss than previously recognized. 

PMID- 26223304
TI  - Influence of Dietary Ascorbic Acid on the Immune Responses of Juvenile Korean
      Rockfish Sebastes schlegelii.
AB  - Juvenile Korean Rockfish Sebastes schlegelii (length, 13.6 +/- 1.4 cm [mean +/-
      SD]; weight, 53.6 +/- 4.2 g) were fed twice daily with diets containing varying
      levels of ascorbic acid (0, 50, 100, 200, and 400 mg/kg) for 4 weeks. Significant
      increases in daily weight and length occurred in fish fed more than 50 mg/kg
      ascorbic acid. The lysozyme activity of fish fed diets containing ascorbic acid
      was considerably increased in rockfish plasma at 400 mg/kg ascorbic acid and in
      kidney at over 50 mg/kg ascorbic acid. Total plasma immunoglobulin M (IgM) levels
      were markedly elevated in fish fed 400 mg/kg ascorbic acid. The results suggest
      that dietary ascorbic acid supplementation in juvenile rockfish can induce a
      significant increase in growth and in immunological features such as lysozyme
      activity and plasma IgM levels.

PMID- 26223305
TI  - Automated in situ brain imaging for mapping the Drosophila connectome.
AB  - Mapping the connectome, a wiring diagram of the entire brain, requires large
      scale imaging of numerous single neurons with diverse morphology. It is a
      formidable challenge to reassemble these neurons into a virtual brain and
      correlate their structural networks with neuronal activities, which are measured
      in different experiments to analyze the informational flow in the brain. Here, we
      report an in situ brain imaging technique called Fly Head Array Slice Tomography
      (FHAST), which permits the reconstruction of structural and functional data to
      generate an integrative connectome in Drosophila. Using FHAST, the head capsules
      of an array of flies can be opened with a single vibratome sectioning to expose
      the brains, replacing the painstaking and inconsistent brain dissection process.
      FHAST can reveal in situ brain neuroanatomy with minimal distortion to neuronal
      morphology and maintain intact neuronal connections to peripheral sensory organs.
      Most importantly, it enables the automated 3D imaging of 100 intact fly brains in
      each experiment. The established head model with in situ brain neuroanatomy
      allows functional data to be accurately registered and associated with 3D images
      of single neurons. These integrative data can then be shared, searched,
      visualized, and analyzed for understanding how brain-wide activities in different
      neurons within the same circuit function together to control complex behaviors. 

PMID- 26223306
TI  - Decreased VEGF-A and sustained PEDF expression in a human retinal pigment
      epithelium cell line cultured under hypothermia.
AB  - BACKGROUND: Previous reports have described a decrease in retinal temperature and
      clinical improvement of wet age-related macular degeneration (AMD) after
      vitrectomy. We hypothesized that the retinal temperature decrease after
      vitrectomy plays a part in the suppression of wet AMD development. To test this
      hypothesis, we evaluated the temperature dependence of the expression of vascular
      endothelial growth factor-A (VEGF-A) and in vitro angiogenesis in retinal pigment
      epithelium (RPE). RESULTS: We cultured ARPE-19 cells at 37, 35, 33 and 31 
      degrees C and measured the expression of VEGF-A, VEGF-A splicing variants, and
      pigment epithelium-derived factor (PEDF). We performed an in vitro tube formation
      assay. The dehydrogenase activity was also evaluated at each temperature.
      Expression of VEGF-A significantly decreased with decreased temperature while
      PEDF expression did not. VEGF165 expression and in vitro angiogenesis also were
      temperature dependent. The dehydrogenase activity significantly decreased as the
      culture temperature decreased. CONCLUSIONS: RPE cultured under hypothermia that
      decreased cellular metabolism also had decreased VEGF-A and sustained PEDF
      expression, creating an anti-angiogenic environment. This mechanism may be
      associated with a beneficial effect after vitrectomy in patients with wet AMD.

PMID- 26223307
TI  - A novel process-based model of microbial growth: self-inhibition in Saccharomyces
      cerevisiae aerobic fed-batch cultures.
AB  - BACKGROUND: Microbial population dynamics in bioreactors depend on both nutrients
      availability and changes in the growth environment. Research is still ongoing on
      the optimization of bioreactor yields focusing on the increase of the maximum
      achievable cell density. RESULTS: A new process-based model is proposed to
      describe the aerobic growth of Saccharomyces cerevisiae cultured on glucose as
      carbon and energy source. The model considers the main metabolic routes of
      glucose assimilation (fermentation to ethanol and respiration) and the occurrence
      of inhibition due to the accumulation of both ethanol and other self-produced
      toxic compounds in the medium. Model simulations reproduced data from classic and
      new experiments of yeast growth in batch and fed-batch cultures. Model and
      experimental results showed that the growth decline observed in prolonged fed
      batch cultures had to be ascribed to self-produced inhibitory compounds other
      than ethanol. CONCLUSIONS: The presented results clarify the dynamics of
      microbial growth under different feeding conditions and highlight the relevance
      of the negative feedback by self-produced inhibitory compounds on the maximum
      cell densities achieved in a bioreactor.

PMID- 26223308
TI  - Identifying new sex-linked genes through BAC sequencing in the dioecious plant
      Silene latifolia.
AB  - BACKGROUND: Silene latifolia represents one of the best-studied plant sex
      chromosome systems. A new approach using RNA-seq data has recently identified
      hundreds of new sex-linked genes in this species. However, this approach is
      expected to miss genes that are either not expressed or are expressed at low
      levels in the tissue(s) used for RNA-seq. Therefore other independent approaches
      are needed to discover such sex-linked genes. RESULTS: Here we used 10 well
      characterized S. latifolia sex-linked genes and their homologs in Silene
      vulgaris, a species without sex chromosomes, to screen BAC libraries of both
      species. We isolated and sequenced 4 Mb of BAC clones of S. latifolia X and Y and
      S. vulgaris genomic regions, which yielded 59 new sex-linked genes (with S.
      vulgaris homologs for some of them). We assembled sequences that we believe
      represent the tip of the Xq arm. These sequences are clearly not pseudoautosomal,
      so we infer that the S. latifolia X has a single pseudoautosomal region (PAR) on
      the Xp arm. The estimated mean gene density in X BACs is 2.2 times lower than
      that in S. vulgaris BACs, agreeing with the genome size difference between these
      species. Gene density was estimated to be extremely low in the Y BAC clones. We
      compared our BAC-located genes with the sex-linked genes identified in previous
      RNA-seq studies, and found that about half of them (those with low expression in
      flower buds) were not identified as sex-linked in previous RNA-seq studies. We
      compiled a set of ~70 validated X/Y genes and X-hemizygous genes (without Y
      copies) from the literature, and used these genes to show that X-hemizygous genes
      have a higher probability of being undetected by the RNA-seq approach, compared
      with X/Y genes; we used this to estimate that about 30% of our BAC-located genes
      must be X-hemizygous. The estimate is similar when we use BAC-located genes that
      have S. vulgaris homologs, which excludes genes that were gained by the X
      chromosome. CONCLUSIONS: Our BAC sequencing identified 59 new sex-linked genes,
      and our analysis of these BAC-located genes, in combination with RNA-seq data
      suggests that gene losses from the S. latifolia Y chromosome could be as high as
      30 %, higher than previous estimates of 10-20%.

PMID- 26223309
TI  - Telecoaching plus a portion control plate for weight care management: a
      randomized trial.
AB  - BACKGROUND: Obesity is a leading preventable cause of death and disability and is
      associated with a lower health-related quality of life. We evaluated the impact
      of telecoaching conducted by a counselor trained in motivational interviewing
      paired with a portion control plate for obese patients in a primary care setting.
      METHODS: We conducted a randomized, clinical trial among patients in a primary
      care practice in the midwestern United States. Patients were randomized to either
      usual care or an intervention including telecoaching with a portion control
      plate. The intervention was provided during a 3-month period with follow-up of
      all patients through 6 months after randomization. The primary outcomes were
      weight, body mass index (BMI),waist circumference, and waist to hip ratio
      measured at baseline, 6, 12, 18, and 24 weeks. Secondary outcomes included
      measures assessing eating behaviors, self-efficacy, and physical activity at
      baseline and at 12 and 24 weeks. RESULTS: A total of 1,101 subjects were pre
      screened, and 90 were randomly assigned to telecoaching plus portion control
      plate (n = 45) or usual care (n = 45). Using last-value carried forward without
      adjustment for baseline demographics, significant reductions in BMI (estimated
      treatment effect -0.4 kg/m(2), P = .038) and waist to hip ratio (estimated
      treatment effect -.02, P = .037) at 3 months were observed in the telecoaching
      plus portion control plate group compared to usual care. These differences were
      not statistically significant at 6 months. In females, the telecoaching plus
      portion control plate intervention was associated with significant reductions in
      weight and BMI at both 3 months (estimated treatment effect -1.6 kg, P = .016 and
      -0.6 kg/m(2), P = .020) and 6 months (estimated treatment effect -2.3 kg, P =
      .013 and -0.8 kg/m(2), P = .025). In males, the telecoaching plus portion control
      intervention was associated with a significant reduction in waist to hip ratio at
      3 months (estimated treatment effect -0.04, P = .017), but failed to show a
      significant difference in weight and BMI. CONCLUSION: Telecoaching with a portion
      control plate can produce positive change in body habitus among obese primary
      care patients; however, changes depend upon sex. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02373878, 13 February 2015.
      https://clinicaltrials.gov/ct2/show/NCT02373878.

PMID- 26223310
TI  - Cost-effectiveness of Interferon-free therapy for Hepatitis C in Germany--an
      application of the efficiency frontier approach.
AB  - BACKGROUND: The approval of direct-acting antivirals for Interferon-free
      treatment revolutionized the therapy of chronic Hepatitis C infection. As of
      August 2014, two treatment regimens for genotype 1 infection received conditional
      approval in the European Union: Sofosbuvir and Ribavirin for 24 weeks and
      Sofosbuvir and Simeprevir with or without Ribavirin for 12 weeks. We aim to
      analyze the cost-effectiveness of both regimens in Germany. METHODS: We set up a
      Markov model with a lifetime horizon to simulate immediate treatment success and
      long-term disease progression for treatment-naive patients. The model analyzes
      both short-term and long-term costs and benefits from the perspective of the
      German Statutory Health Insurance. We apply the efficiency frontier method, which
      was suggested by German Institute for Quality and Efficiency in Health Care for
      cost-effectiveness analysis in Germany. RESULTS: The efficiency frontier is
      defined by dual therapy and first generation direct-acting antiviral Boceprevir,
      yielding a maximum of ? 1,447.69 per additional percentage point of sustained
      virologic response gained. Even without rebates, Sofosbuvir/Simeprevir is very
      close with ? 1,560.13 per additional percentage point. It is both more effective
      and less expensive than Sofosbuvir/Ribavirin. CONCLUSIONS: In addition to higher
      sustained virologic response rates, new direct-acting antivirals save long-term
      costs by preventing complications such as liver cirrhosis, hepatocellular
      carcinoma and ultimately liver transplants, thereby offsetting part of higher
      drug costs. Our findings are in line with the guidance published by German
      Society for Gastroenterology, Digestive and Metabolic Diseases, which recommends
      Sofosbuvir/Simeprevir for Interferon ineligible or intolerant patients.

PMID- 26223303
TI  - Quality and quantity of TFH cells are critical for broad antibody development in
      SHIVAD8 infection.
AB  - Broadly neutralizing antibodies (bNAbs) protect against HIV-1 infection, yet how
      they are generated during chronic infection remains unclear. It is known that T
      follicular helper (TFH) cells are needed to promote affinity maturation of B
      cells during an immune response; however, the role of TFH during HIV-1 infection
      is undefined within lymph node germinal centers (GCs). We use nonhuman primates
      to investigate the relationship in the early stage of chronic SHIVAD8 (simian
      human immunodeficiency virus AD8) infection between envelope (Env)-specific TFH
      cells, Env-specific B cells, virus, and the generation of bNAbs during later
      infection. We found that both the frequency and quality of Env-specific TFH cells
      were associated with an expansion of Env-specific immunoglobulin G-positive GC B
      cells and broader neutralization across HIV clades. We also found a correlation
      between breadth of neutralization and the degree of somatic hypermutation in Env
      specific memory B cells. Finally, we observed high viral loads and greater
      diversity of Env sequences in rhesus macaques that developed cross-reactive
      neutralization as compared to those that did not. These studies highlight the
      importance of boosting high-quality TFH populations as part of a robust vaccine
      regimen aimed at eliciting bNabs. 

PMID- 26223312
TI  - The reliability and minimal detectable change of Timed Up and Go test in
      individuals with grade 1-3 knee osteoarthritis.
AB  - BACKGROUND: The Timed Up and Go (TUG) test is quick and easy tests to assess
      patients' functional mobility. However, its reliability in individuals with knee
      osteoarthritis (OA) has not been well established. The aims of this study were to
      determine the reliability and minimal detectable change of the TUG test in
      individuals with doubtful to moderate (Grade 1-3) knee OA. METHODS: Sixty-five
      subjects (25 male, 40 female), aged 45-70 years, with knee OA participated. Inter
      rater reliability was assessed using two observers at different times of the same
      day in an alternating order. Intra-rater reliability was assessed on two
      consecutive visits with a 2-day interval. The standard error of measurement (SEM)
      and the minimum detectable change (MDC) were calculated to determine
      statistically meaningful changes. RESULTS: Intra-rater and inter-rater
      reliability were 0.97 (95% confidence interval [CI], 0.95 - 0.98) and 0.96 (95%
      confidence interval [CI], 0.94 - 0.97), respectively. The MDC, based on
      measurements by a single rater and between raters, was 1.10 and 1.14 seconds,
      respectively. CONCLUSIONS: The TUG is a reliable test with adequate MDC for
      clinical use in individuals with doubtful to moderate knee OA.

PMID- 26223311
TI  - Targeting anti-apoptotic Bcl-2 by AT-101 to increase radiation efficacy: data
      from in vitro and clinical pharmacokinetic studies in head and neck cancer.
AB  - BACKGROUND: Pro-survival Bcl-2 family members can promote cancer development and
      contribute to treatment resistance. Head and neck squamous cell carcinoma (HNSCC)
      is frequently characterized by overexpression of anti-apoptotic Bcl-2 family
      members. Increased levels of these anti-apoptotic proteins have been associated
      with radio- and chemoresistance and poor clinical outcome. Inhibition of anti
      apoptotic Bcl-2 family members therefore represents an appealing strategy to
      overcome resistance to anti-cancer therapies. The aim of this study was to
      evaluate combined effects of radiation and the pan-Bcl-2 inhibitor AT-101 in
      HNSCC in vitro. In addition, we determined human plasma levels of AT-101 obtained
      from a phase I/II trial, and compared these with the effective in vitro
      concentrations to substantiate therapeutic opportunities. METHODS: We examined
      the effect of AT-101, radiation and the combination on apoptosis induction and
      clonogenic survival in two HNSCC cell lines that express the target proteins.
      Apoptosis was assessed by bis-benzimide staining to detect morphological nuclear
      changes and/or by propidium iodide staining and flow-cytometry analysis to
      quantify sub-diploid apoptotic nuclei. The type of interaction between AT-101 and
      radiation was evaluated by calculating the Combination Index (CI) and by
      performing isobolographic analysis. For the pharmacokinetic analysis, plasma AT
      101 levels were measured by HPLC in blood samples collected from patients
      enrolled in our clinical phase I/II study. These patients with locally advanced
      HNSCC were treated with standard cisplatin-based chemoradiotherapy and received
      dose-escalating oral AT-101 in a 2-weeks daily schedule every 3 weeks. RESULTS:
      In vitro results showed that AT-101 enhances radiation-induced apoptosis with
      CI's below 1.0, indicating synergy. This effect was sequence-dependent.
      Clonogenic survival assays demonstrated a radiosensitizing effect with a DEF37 of
      1.3 at sub-apoptotic concentrations of AT-101. Pharmacokinetic analysis of
      patient blood samples taken between 30 min and 24 h after intake of AT-101 showed
      a dose-dependent increase in plasma concentration with peak levels up to 300-700
      ng/ml between 1.5 and 2.5 h after intake. CONCLUSION: AT-101 is a competent
      enhancer of radiation-induced apoptosis in HNSCC in vitro. In addition, in vitro
      radiosensitization was observed at clinically attainable plasma levels. These
      finding support further evaluation of the combination of AT-101 with radiation in
      Bcl-2-overexpressing tumors.

PMID- 26223313
TI  - Population-based SEER trend analysis of overall and cancer-specific survival in
      5138 patients with gastrointestinal stromal tumor.
AB  - BACKGROUND: The objective of the present population-based analysis was to assess
      survival patterns in patients with resected and metastatic GIST. METHODS:
      Patients with histologically proven GIST were extracted from the Surveillance,
      Epidemiology and End Results (SEER) database from 1998 through 2011. Survival was
      determined applying Kaplan-Meier-estimates and multivariable Cox-regression
      analyses. The impact of size and mitotic count on survival was assessed with a
      generalized receiver-operating characteristic-analysis. RESULTS: Overall, 5138
      patients were included. Median age was 62 years (range: 18-101 years), 47.3% were
      female, 68.8% Caucasians. GIST location was in the stomach in 58.7% and small
      bowel in 31.2%. Lymph node and distant metastases were found in 5.1 and 18.0%,
      respectively. For non-metastatic GIST, three-year overall survival increased from
      68.5% (95 % CI: 58.8-79.8%) in 1998 to 88.6% (95 % CI: 85.3-92.0%) in 2008,
      cancer-specific survival from 75.3% (95 % CI: 66.1-85.9%) in 1998 to 92.2% (95 %
      CI: 89.4-95.1%) in 2008. For metastatic GIST, three-year overall survival
      increased from 15.0% (95 % CI: 5.3-42.6%) in 1998 to 54.7% (95 % CI: 44.4-67.3%)
      in 2008, cancer-specific survival from 15.0% (95 % CI: 5.3-42.6%) in 1998 to
      61.9% (95 % CI: 51.4-74.5%) in 2008 (all PTrend < 0.05). CONCLUSIONS: This is the
      first SEER trend analysis assessing outcomes in a large cohort of GIST patients
      over a 11-year time period. The analysis provides compelling evidence of a
      statistically significant and clinically relevant increase in overall and cancer
      specific survival from 1998 to 2008, both for resected as well as metastatic
      GIST.

PMID- 26223315
TI  - Clinical Observations About The Strange Case of Dr. Jekyll and Mr. Hyde in
      Relation to Bipolar Disorder.

PMID- 26223316
TI  - Experiences of Psychological Distress and Sources of Stress and Support During
      Medical Training: a Survey of Medical Students.
AB  - OBJECTIVE: The authors examine the prevalence of psychological distress, the
      stressors experienced, and the supports used by medical students and residents
      during their medical training at a Canadian university. METHOD: This study used
      an online survey that included a standardized instrument to evaluate
      psychological distress (Kessler-10) and Likert-based survey items that examined
      stress levels related to family relationships, living accommodations, commuting,
      finances, and program requirements. Depressive symptoms, substance use, and
      suicidal ideation were also measured, as were supports accessed (e.g.,
      counseling) and students' perceptions of the overall supportiveness of the
      university. Non-parametric descriptive statistics were used to examine the
      prevalence of psychological distress, sources of stress, and supports accessed.
      RESULTS: Surveys were received from 381 students (37% response). Most students
      (60%) reported normal levels of psychological distress on the K10 (M = 19.5, SD =
      6.25), and a subgroup reported high to very high levels of psychological
      distress. A small number also reported substance use, symptoms of depression,
      and/or suicidal ideation. CONCLUSION: These results indicate that students
      experience psychological distress from a number of stressors and suggest that
      medical schools should act as key partners in supporting student well-being by
      promoting self-care, educating students on the risks of burnout, and developing
      programs to support at-risk students.

PMID- 26223317
TI  - Metabolism and toxicokinetics of 1,4-dioxane in humans after inhalational
      exposure at rest and under physical stress.
AB  - The present study investigated the toxicokinetics of 1,4-dioxane in humans
      exposed at rest and during physical stress. Eighteen volunteers were divided into
      three groups of six individuals each, who were exposed separately in three
      experiments to 20 ppm (73 mg/m(3)) 1,4-dioxane for 8 h. The first group was
      exposed at rest (Experiment 1), whereas the other groups performed exercises on a
      bicycle ergometer for 10 min every hour, corresponding to a physical exercise of
      50 W (Experiment 2) and 75 W (Experiment 3), respectively. Blood samples were
      collected after 4 and 8 h, and all urine samples were collected over 24 h. The
      samples were analysed for 1,4-dioxane and its metabolite 2-(2
      hydroxyethoxy)acetic acid (HEAA). The amount of urinary-eliminated HEAA increased
      during exposure and showed its maximum 9.8 +/- 1.9 h after the beginning of
      exposure. The levels of 1,4-dioxane in blood and urine, however, barely rose
      above the limit of detection. Depending on the physical stress of the volunteers,
      the maximum elimination rate of HEAA in urine was significantly increased with
      23.2 +/- 7.7, 30.4 +/- 7.2 and 41.8 +/- 23.8 mg/h for Experiments 1, 2 and 3,
      respectively. Likewise, the cumulative HEAA excretion over 24 h increased with
      increasing physical stress; 53 +/- 15 % of the theoretical inhaled 1,4-dioxane
      dose was excreted as HEAA in urine during the first 24 h. The average maximum
      level of HEAA ranged between 378 and 451 mg/g creatinine and increased with the
      applied physical stress. The half-life of HEAA was found to be 3.4 +/- 0.5 h.
      Twenty-four hours after the beginning of the exposure, 31-51 mg HEAA/g creatinine
      were still detected in urine, indicating only a low accumulation of the
      metabolite during a working week. The study results revealed an increasing effect
      of the applied physical stress on the total eliminated amounts of HEAA as well as
      on the maximum HEAA levels at the end of exposure. For the estimation of
      biomonitoring equivalents to occupational exposure limits, this effect should be
      taken into account. 

PMID- 26223318
TI  - Selective cancer-killing ability of metal-based nanoparticles: implications for
      cancer therapy.
AB  - There has been little focus on the promising ability of metal-based nanoparticles
      (NPs) to kill cancer cells while sparing normal cells. Many in vitro and in vivo
      reports suggest that certain metal-based NPs are able to induce apoptosis and
      autophagy in cancer cells at specific concentrations that are not significantly
      toxic to non-cancerous cells. Those NPs are thought to exploit the oxidative
      stress conditions that prevail in cancer cells, which are largely exhausted of
      antioxidant ability. This review considers the induction of reactive oxygen
      species (ROS) by metal-based NPs as a mechanism for the specific killing of
      cancer cells. The article concomitantly provides a comprehensive description of
      the important pathways and molecules leading to programmed cell death (PCD),
      which occurs mainly via apoptosis, autophagy, and necroptosis. The PCD pathways
      are followed as ROS-burdened cancer cells succumb to ROS-generating metal-based
      NPs. Exploration of nanotechnology interventions in anticancer therapy demands
      further research into the mechanism of intracellular induction of ROS by metal
      based NPs. Furthermore, the induction of ROS by NPs should be strictly controlled
      if ROS-based therapy is to become a paradigm in cancer therapy. 

PMID- 26223319
TI  - Endoplasmic reticulum stress and Oxidative stress in the pathogenesis of Non
      alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of
      metabolic syndrome. The underlying causes of the disease progression in NAFLD are
      unclear. Recent evidences suggest endoplasmic reticulum stress in the development
      of lipid droplets (steatosis) and subsequent generation of reactive oxygen
      species (ROS) in the progression to non-alcoholic steatohepatitis (NASH). The
      signalling pathway activated by disruption of endoplasmic reticulum (ER)
      homoeostasis, called as unfolded protein response, is linked with membrane
      biosynthesis, insulin action, inflammation and apoptosis. ROS are important
      mediators of inflammation. Protein folding in ER is linked to ROS. Therefore
      understanding the basic mechanisms that lead to ER stress and ROS in NAFLD have
      become the topics of immense interest. The present review focuses on the role of
      ER stress and ROS in the pathogenesis of NAFLD. We also highlight the cross talk
      between ER stress and oxidative stress which suggest and encourage the
      development of therapeutics for NAFLD. Further we have reviewed various
      strategies used for the management of NAFLD/NASH and limitations of such
      strategies. Our review therefore highlights the need for newer strategies with
      regards to ER stress and oxidative stress. 

PMID- 26223320
TI  - Chicken skin virome analyzed by high-throughput sequencing shows a composition
      highly different from human skin.
AB  - Recent studies show that human skin at homeostasis is a complex ecosystem whose
      virome include circular DNA viruses, especially papillomaviruses and
      polyomaviruses. To determine the chicken skin virome in comparison with human
      skin virome, a chicken swabs pool sample from fifteen indoor healthy chickens of
      five genetic backgrounds was examined for the presence of DNA viruses by high
      throughput sequencing (HTS). The results indicate a predominance of herpesviruses
      from the Mardivirus genus, coming from either vaccinal origin or presumably
      asymptomatic infection. Despite the high sensitivity of the HTS method used
      herein to detect small circular DNA viruses, we did not detect any
      papillomaviruses, polyomaviruses, or circoviruses, indicating that these viruses
      may not be resident of the chicken skin. The results suggest that the turkey
      herpesvirus is a resident of chicken skin in vaccinated chickens. This study
      indicates major differences between the skin viromes of chickens and humans. The
      origin of this difference remains to be further studied in relation with skin
      physiology, environment, or virus population dynamics. 

PMID- 26223321
TI  - Toward structured peer support interventions in oncology: a qualitative insight
      into the experiences of gynaecological cancer survivors providing peer support.
AB  - PURPOSE: Research into dyadic (one-to-one) peer support has predominantly focused
      on the recipients of peer support whilst neglecting the impact on the peer
      support providers (PSPs). Increasingly, structured/protocolised peer support
      interventions are employed. The aim of this qualitative study was to explore the
      experience of providing peer support within a protocolised intervention and how
      common key characteristics of such interventions (guidelines and checklists,
      rigorous training and partnerships with health professionals) may influence PSPs'
      experiences. This research was conducted within the context of an ongoing
      randomised controlled trial investigating a protocolised peer support
      intervention (the Peer and Nurse support Trial to Assist women in Gynaecological
      Oncology (PeNTAGOn) study). METHODS: Eleven women (gynaecological cancer
      survivors) providing peer support within the PeNTAGOn study participated in semi
      structured telephone interviews. Transcribed interviews were analysed using
      interpretative phenomenological analysis. RESULTS: Five key themes were
      identified which described the overall experience of providing protocolised peer
      support: (i) fitting oneself to the protocolised PSP role, (ii) the impact of
      personal beliefs about the value of research, (iii) protocolisation as both
      blessing and curse, (iv) discussing taboo or sensitive topics and (v) the impact
      of interactions with study personnel. CONCLUSIONS: These insights into the
      advantages and disadvantages of protocolised peer support can be used to inform
      future research and social support programs and maximise the effectiveness of
      such programs for patients, PSPs and the health-care system.

PMID- 26223322
TI  - Mutant p53 promotes ovarian cancer cell adhesion to mesothelial cells via
      integrin beta4 and Akt signals.
AB  - Missense mutations in the TP53 gene resulting in the accumulation of mutant
      proteins are extremely common in advanced ovarian cancer, which is characterised
      by peritoneal metastasis. Attachment of cancer cells to the peritoneal
      mesothelium is regarded as an initial, key step for the metastatic spread of
      ovarian cancer. In the present study, we investigated the possible role of a p53
      mutant in the mesothelial adhesion of ovarian cancer cells. We found that OVCAR-3
      cells with the R248 TP53 mutation (p53(R248)) were more adhesive to mesothelial
      Met5A cells than were A2780 cells expressing wild-type p53. In addition, ectopic
      expression of p53(R248) in p53-null SKOV-3 cells significantly increased adhesion
      to Met5A cells. Knockdown of mutant p53 significantly compromised p53(R248)
      induced cell adhesion to Met5A cells. Microarray analysis revealed that several
      adhesion-related genes, including integrin beta4, were markedly up-regulated, and
      certain signalling pathways, including PI3K/Akt, were activated in p53(R248)
      transfectants of SKOV-3 cells. Inhibition of integrin beta4 and Akt signalling
      using blocking antibody and the inhibitor LY294002, respectively, significantly
      attenuated p53(R248)-mediated ovarian cancer-mesothelial adhesion. These data
      suggest that the p53(R248) mutant endows ovarian cancer cells with increased
      adhesiveness and that integrin beta4 and Akt signalling are associated with the
      mutation-enhanced ovarian cancer-mesothelial cell adhesion. 

PMID- 26223323
TI  - Effect of ultra-low-dose estriol and lactobacilli vaginal tablets (Gynoflor(r))
      on inflammatory and infectious markers of the vaginal ecosystem in postmenopausal
      women with breast cancer on aromatase inhibitors.
AB  - This study was a detailed microscopic analysis of the changes of vaginal
      microflora characteristics after application of 0.03 mg estriol-lactobacilli
      combination on the vaginal ecosystem in postmenopausal breast cancer (BC)
      survivors on aromatase inhibitors (AI) with severe atrophic vaginitis. A total of
      16 BC women on AI applied daily one vaginal tablet of Gynoflor(r) for 28 days
      followed by a maintenance therapy of three tablets weekly for 8 weeks. During
      four follow up visits a smear from the upper lateral vaginal wall was analysed by
      phase contrast microscopy at 400 times magnification in order to classify the
      lactobacillary grades(LBG), bacterial vaginosis (BV), aerobic vaginitis (AV),
      vulvovaginal candidosis (VVC), proportional number of leukocytes and evidence of
      parabasal cells and epitheliolysis. LBG improved from 81% LBG-III at entry to 88%
      LBG-I&IIa after 2 weeks of initial therapy, which further improved upon follow up
      (p < 0.001). Whereas BV was a rare event, AV was frequent and substantially
      improved during treatment (p < 0.01). While at entry most patients had moderate
      or severe AV, after maintenance therapy no patient except one had AV. The number
      of leukocytes dropped dramatically from a score of 1.78 +/- 0.70 to 1.06 +/- 0.25
      which was consistent till the end of the study (p < 0.01). Parabasal cells
      dropped from a score of 3.4 +/- 0.64 at entry to 1.3 +/- 0.60 at the final visit
      (p trend < 0.01). Starting from a low rate of Candida colonisation of 2/14 (14%),
      a sudden rise to 7/16 (44%) occurred after 2 weeks, to return back to base levels
      at subsequent visits. The vaginal use of ultra-low dose estriol and lactobacilli
      results in rapid and enduring improvement of all markers of the vaginal
      microflora and epithelial vaginal cell quality in women with breast cancer on AI
      with dyspareunia. Candida may develop soon after its use, but rapidly disappears
      again upon their prolonged use. Due to its excellent safety profiles and clinical
      efficacy we recommend this product as first choice in women on AI with severe
      dyspareunia.

PMID- 26223324
TI  - Clinical characteristics of 154 patients suspected of having Ebola virus disease
      in the Ebola holding center of Jui Government Hospital in Sierra Leone during the
      2014 Ebola outbreak.
AB  - This article sought to analyze the clinical features of 154 patients suspected of
      having Ebola virus disease (EVD) in an Ebola holding center in Sierra Leone from
      October 1 through November 9, 2014. We found that 108 of the 154 patients were
      confirmed with EVD. Eighty-five had known outcomes. Forty-nine of the 85 patients
      had been exposed to EVD. The average mortality rate was 60%. The mean interval
      between the onset of symptoms and hospitalization was 5.8 +/- 3.3 days. The mean
      incubation period was 9.2 +/- 6.7 days. Common symptoms of the EVD patients on
      admission were fatigue (85.2%), anorexia (84.3%), fever (75.9%), and headache
      (72.2%). Our data showed that the total symptoms of confirmed EVD patients were
      significantly higher than those of non-EVD patients (9 vs. 5.5; p < 0.001). The
      likelihood of EVD was 87.6% when a patient presented more than 6 out of 21
      symptoms on admission. The survivors were significantly younger than non
      survivors (24.0 +/- 10.0 years vs. 31.3 +/- 15.3 years; p = 0.016). The real-time
      polymerase chain reaction (PCR) analysis showed that, in the survivors, the virus
      load was significantly lower (Ct value: 25.2 +/- 4.1 vs. 28.7 +/- 5.7; p =
      0.002). Multivariate analysis showed that age, fever, and viral load were
      independent predictors of mortality. Taken together, our data suggested that a
      cutoff of six symptoms could be used to predict patients with high or low risk of
      EVD. It seemed that age, fever, and viral load were the main risk factors
      associated with EVD mortality.

PMID- 26223326
TI  - The impact of the global economic crisis on HIV and AIDS programmes directed at
      women and children in Zambia.
AB  - This investigation sought to ascertain the extent to which the global economic
      crisis of 2008-2009 affected the delivery of HIV/AIDS-related services directed
      at pregnant and lactating mothers, children living with HIV and children orphaned
      through HIV in Zambia. Using a combined macroeconomic analysis and a multiple
      case study approach, the authors found that from mid-2008 to mid-2009 the Zambian
      economy was indeed buffeted by the global economic crisis. During that period the
      case study subjects experienced challenges with respect to the funding, delivery
      and effectiveness of services that were clearly attributable, directly or
      indirectly, to the global economic crisis. The source of funding most often
      compromised was external private flows. The services most often compromised were
      non-medical services (such as the delivery of assistance to orphans and
      counselling to HIV-positive mothers) while the more strictly medical services
      (such as antiretroviral therapy) were protected from funding cuts and service
      interruptions. Impairments to service effectiveness were experienced relatively
      equally by (HIV-positive) pregnant women and lactating mothers and children
      orphaned through HIV. Children living with AIDS were least affected because of
      the primacy of ARV therapy in their care. 

PMID- 26223325
TI  - Actin-related protein 2/3 complex-based actin polymerization is critical for male
      fertility.
AB  - The actin-related protein 2/3 (Arp2/3) complex is critical for regulation of
      actin polymerization, which is associated with sperm motility and capacitation
      status. However, the function of the Arp2/3 complex in male fertility has not yet
      been fully elucidated. Therefore, this study was designed to investigate the role
      of the Arp2/3 complex in different processes in spermatozoa and its consequences
      on fertilization and early embryonic development. In this in vitro study, mouse
      spermatozoa were incubated with different concentrations (10, 100, and 500 MUm)
      of CK-636, an Arp2/3 complex antagonist. Our results demonstrated that inhibition
      of the Arp2/3 complex by high concentrations (100 and 500 MUm) of CK-636 induced
      hyper-activated motility and acrosomal reaction, whereas intracellular calcium
      and tyrosine phosphorylation levels in spermatozoa were inhibited. Moreover,
      exposure of spermatozoa to the highest concentration of CK-636 reduced
      fertilization and embryo development. Interestingly, fertilization was
      significantly increased after treatment with 100 MUm CK-636, whereas embryonic
      development was significantly decreased. Therefore, we conclude that the Arp2/3
      complex plays a decisive role in regulation of sperm function and male fertility
      via actin polymerization. We anticipate that the Arp2/3 complex may have clinical
      application as marker for male fertility and male contraceptive targeting. 

PMID- 26223327
TI  - HIV health literacy, sexual behaviour and self-reports of having tested for HIV
      among students.
AB  - The HIV prevalence among young South African adults makes it important to
      understand their HIV knowledge, sexual behaviour and HIV counselling and testing
      (HCT) behaviour in this group. This paper presents the demographics, knowledge,
      sexual behaviour and cues to action as reported by sexually active students' who
      had HCT. A cross-sectional study conducted in 10 high schools in the eThekwini
      and Ugu districts, KwaZulu-Natal, surveyed students' HIV knowledge, sexual
      behaviour and HCT behaviour. Complete information was available from 1 114
      (97.9%) students who participated in the survey. Of these, 378 (33.9%) were
      sexually active and were included in this analysis. Logistic regression models
      tested for significant associations between the independent and the dependent
      variables under study, nesting the students within schools and controlling for
      age, sex, grade and school location (urban/rural).The median age of students was
      17 years (range: 14-23 years) with most being male (n=287; 75.9%). The lifetime
      median number of sexual partners of students was 3 (range: 1-27). Students who
      used condoms with their regular partners were more likely to have had counselling
      for HIV (OR :1.79; 95% CI: 1.06-3.01). Those students who were more likely to
      have been tested for HIV were female (OR: 44.90; 95% CI: 7.77-259.38), those who
      had always used a condom with their non-regular partner (OR: 2.75; 95% CI: 1.01
      7.47), and those who knew a person who had tested for HIV (OR: 15.28; 95% CI:
      5.16-45.23). Targeting students, especially males early in adolescence and
      reinforcing safe sex behaviour messages through their high school years, can
      encourage HCT among students. 

PMID- 26223328
TI  - On the road again: concurrency and condom use among Uganda truck drivers.
AB  - Long-distance truck drivers have been shown to be a critical population in the
      spread of HIV in Africa. In 2009, surveys with 385 Ugandan long-distance truck
      drivers measured concurrency point prevalence with two methods; it ranged from
      37.4% (calendar-method) to 50.1% (direct question). The majority (84%) of
      relationships reported were long-term resulting in a long duration of overlap
      (average of 58 months) across concurrent partnerships. Only 7% of these men
      reported using any condoms with their spouses during the past month. Among all
      non-spousal relationships, duration of relationship was the factor most strongly
      associated with engaging in unprotected sex in the past month in a multivariable
      analyses controlling for partner and relationship characteristics. Innovative
      intervention programs for these men and their partners are needed that address
      the realities of truck drivers' lifestyles. 

PMID- 26223329
TI  - Factors associated with mothers' decisions on male neonatal circumcision in
      Swaziland.
AB  - Neonatal male circumcision is safer, easier and cheaper than adult male
      circumcision, but is not widely practised in Swaziland. It has been suggested as
      one of several ways of controlling the spread of HIV. We conducted research aimed
      at assessing mothers' knowledge, attitudes and perceptions towards circumcision
      and reasons why mothers have their newly born male children circumcised. A cross
      sectional study was conducted at Hlatikulu Government Hospital, a rural hospital
      in Shiselweni region, Swaziland. The target population was mothers with children
      younger than 6 months old who presented at the hospital. Of the 392 participants
      who were interviewed, 43 (11.2%) had circumcised their children. The
      participants' ages ranged from 15 to 44 with a mean age of 25.3 years. All the
      respondents had a mean knowledge score of 7.8 out of a maximum possible of 11, a
      mean attitudes score of 3.6 out of 6 and a mean perception score of 1.8 out of 3.
      The main reasons for mothers circumcising their children were to keep the penile
      organ clean (97.7%), to reduce sexually transmitted infections when one is
      sexually active (97.7%) and to reduce HIV transmission (97.7%). Participants who
      did not circumcise their children cited mainly that their spouses did not approve
      (84.5%), that they were anxious about complications after the operation (44.4%)
      and fear that their newborns would feel pain (54.4%). The mothers in this study
      had high knowledge, positive attitudes and perceptions towards male neonatal
      circumcision, but the circumcision levels are still very low. Interventions need
      to be directed towards providing accurate information and resources that
      facilitate mothers, and to a greater extend fathers, in making the decision to
      circumcise their male children and being able to act on that decision. 

PMID- 26223330
TI  - Attracting female sex workers to HIV testing and counselling in Ethiopia: a
      qualitative study with sex workers in Addis Ababa.
AB  - Despite growing efforts to increase HIV testing and counselling (HTC) services
      for most at risk populations in Ethiopia, the use of these services by female sex
      workers (FSWs) remains low. With rising numbers of FSWs in Addis Ketema and
      concerns about their high risk behaviours, exploring and addressing the barriers
      to uptake is crucial. This qualitative study explores the barriers to utilising
      HTC facilities and identifies the motives and motivations of FSWs who seek HTC
      through in-depth and semi-structured interviews with female sex workers,
      healthcare workers and key informants. Results indicate that FSWs face numerous
      barriers including inability to seek treatment if found to be positive due to the
      requirement of an identity (ID) card many do not own. Many FSWs reported
      discriminatory behaviour from healthcare workers and a lack of dedicated
      services. What is clear from the findings is that distinct strategies, which
      differ from those of the broader population, are required to attract FSWs-
      strategies which take into account the barriers and maximise the reported motives
      and motivations for testing.

PMID- 26223331
TI  - "Managing identities" and parental disclosure of HIV sero-status in Zimbabwe.
AB  - Drawing from a small sample of HIV infected respondents, this paper examines
      parents' perceptions on the decision to disclose or not to disclose their HIV
      sero-status to their children. It explores how parents control the information in
      the interactional ritual with their children. The paper uses Goffman's concept of
      dramaturgy to analyse how parents manage and control disclosure within a context
      where HIV and AIDS is associated with stigma. Disclosure is a strategic encounter
      in which the interactants (parents) manage to create a desired identity or spoil
      an identity. Qualitative research incorporating focus group discussions and in
      depth interviews was used to examine the perceptions of parents who are HIV
      positive on disclosure of their status to their children. Such a methodological
      approach allows for a nuanced understanding of the context in which decision to
      disclose status happens. The study findings show that in a social context
      involving parents and children as actors there are complex expectations which
      affect parental disclosure of HIV sero-status to their children. The desire to
      manage an expected identity militated or enabled disclosure in a parental
      relationship. 

PMID- 26223333
TI  - Gender perspectives in care provision and care receipt among older people
      infected and affected by HIV in Uganda.
AB  - The objective of this study was to examine gender roles in the provision and
      receipt of care among older Ugandans. Survey data on care work were collected in
      2009-2010 from 510 older people infected or affected by HIV/AIDS, at one rural
      and one semi-urban site. The questionnaire was adapted from the WHO Study on
      global AGEing and adult health survey. The type of care work done by older men
      and women for children in their households differs, yet, both men and women are
      taking on various types of care work. Women were more likely to report taking
      part in health/personal and physical care, whereas men were more likely to report
      providing financial assistance. Some older people, particularly women, were
      providing care at the same time as needing care. The finding on reciprocity of
      care suggests the need for further studies focused on how the reciprocity of care
      may affect health and well-being in older age. 

PMID- 26223332
TI  - Sexual HIV risk among substance-using female commercial sex workers in Durban,
      South Africa.
AB  - This study examined data collected from a sample of female sex workers (FSWs)
      during the first two years of a brief risk-reduction intervention for vulnerable
      populations that focused on substance use and HIV risk-related behaviours (2007
      2009) as part of a rapid assessment and response evaluation study. In 2007, in
      collaboration with a local non-governmental organisation (NGO), an initiative was
      begun to roll out targeted harm reduction strategies for drug-using street based
      FSWs in Durban, South Africa. Data were collected on demographic characteristics,
      substance use and HIV risk behaviours to tailor these harm reduction strategies
      with participants. Over the first two years of the intervention, data were
      collected from 646 FSWs: 428 who reported being at low risk for HIV and 218 who
      reported being at high risk for HIV (defined as engaging in unprotected sex with
      sexual partners in the past 90 days). FSWs who had previously been diagnosed with
      HIV or a sexually transmitted disease (STD) were significantly less likely to
      report engaging in unprotected sex. Those who used over-the-counter or
      prescription (OTC/PRE) drugs reported engaging in unprotected sex significantly
      more often than FSWs who did not use these substances, while those who used
      heroin were less likely to report unprotected sex. The findings are encouraging
      in that those who are aware of their HIV status are less likely to engage in
      risky sexual behaviour, and therefore HIV testing and counselling is recommended.
      It indicates the need to identify strategies to encourage the likelihood of all
      FSWs, particularly those who are HIV-positive, to use condoms. It also encourages
      further research to investigate specific substances as possible predictors of
      high risk behaviours in high-risk populations of sex workers. 

PMID- 26223334
TI  - The emotional wellbeing of lay HIV counselling and testing counsellors.
AB  - The HIV testing, treatment and care programme of the South African public
      healthcare system depends on HIV counselling and testing (HCT) that is primarily
      delivered by lay counsellors. Lay counsellors are expected to educate clients
      about HIV/AIDS, advocate behaviour change, convey test results and support those
      infected and affected to cope with the emotional and social challenges associated
      with HIV/AIDS. This research focuses on the emotional wellbeing of lay HCT
      counsellors because this influences the quality of services they provide. A mixed
      methods approach was used. The emotional wellbeing, level of burnout, depression
      and coping style of 50 lay HCT counsellors working at the City of Tshwane clinics
      were assessed. Additionally, five focus group discussions were conducted. The
      results showed that HCT counsellors reported average emotional wellbeing, high
      levels of emotional exhaustion and depression. They had a sense of personal
      accomplishment and positive coping skills. The results revealed that they may
      have difficulty dealing with clients' emotional distress without adequate
      training and supervision. This creates a dilemma for service delivery. In the
      light of the important role they play in service delivery, the role of the lay
      HCT counsellor needs to be reconsidered. HCT should develop as a profession with
      specific training and supervision to develop their emotional competencies to
      conduct effective counselling sessions. 

PMID- 26223335
TI  - The epistemology of AIDS in South Africa: lessons from three scenario projects.
AB  - This article reviews the methodology of future scenario-building in the context
      of HIV and AIDS in Africa. It considers three scenario studies conducted in the
      past decade: UNAIDS (2005), Metropolitan Holdings (2006) and the AIDS Governance
      scenarios (2015). The article is a critical reflection of Future Studies
      epistemology which claims to contribute a unique heuristic niche in the study of
      AIDS. The article offers several methodological insights: (1) despite claims to
      the contrary, scenario methodology remains profoundly influenced by existing
      political and research agenda; instead of denying these, scenarists should
      acknowledge this; (2) the utility of scenario studies is strongly influenced by
      their unit of analysis and their time frame, which determine their applicability
      and therefore their policy relevance; and (3) scenario planners should guard
      against perpetuating the myth that this methodology is a crystal ball into the
      future because they are powerful tools for strategic planning about the present,
      rather than the distant future. In addition to these methodological insights, the
      article finds that future scenario studies are useful in identifying significant
      discursive and policy shifts in the AIDS response. 

PMID- 26223336
TI  - Neuroleptic Malignant Syndrome: Complications, Outcomes, and Mortality.
AB  - OBJECTIVE: Our study objective was to identify real-world rates of complications,
      mortality, and outcomes in patients with neuroleptic malignant syndrome (NMS)
      over the last decade in the United States. METHODS: A total of 1346 patients were
      obtained from the nationwide inpatient sample for the years 2002-2011. Common
      complications known to be associated with NMS were identified. Multivariable
      regression analyses were used to identify predictors of mortality. RESULTS: The
      most prevalent complication was rhabdomyolysis (30.1%). Other common
      complications were acute respiratory failure (16.1%), acute kidney injury
      (17.7%), sepsis (6.2%), and other systemic infections. Unadjusted mortality rate
      was 5.6%. Older age, acute respiratory failure, acute kidney injury, sepsis, and
      comorbid congestive heart failure were significant predictors of mortality. Acute
      respiratory failure was the strongest independent mortality predictor (p <
      0.001). CONCLUSION: In our large sample population-based study on NMS, we were
      able to identify the rates of several preselected complications and the
      mortality. The identification of independent mortality predictors in this study
      can guide physicians in the management and prognostication of this rare syndrome.

PMID- 26223337
TI  - Altered regional cortical thickness and subcortical volume in women with primary
      dysmenorrhoea.
AB  - BACKGROUND: There is emerging evidence that primary dysmenorrhoea (PDM) is
      associated with altered brain function and structure. However, few studies have
      investigated changes in regional cortical thickness and subcortical volumes in
      PDM patients. The purpose of this study was to characterize differences in both
      cortical thickness and subcortical volumes between PDM patients and healthy
      controls (HCs). METHODS: T1-weighted magnetic resonance images were obtained from
      44 PDM patients and 32 HCs matched for age and handedness. Cortical thickness was
      compared in multiple locations across the continuous cortical surface, and
      subcortical volumes were compared on a structure-by-structure basis. Correlation
      analysis was then used to evaluate relationships between the clinical symptoms
      and abnormal brain structure in PDM. RESULTS: PDM patients had significantly
      increased cortical thickness in the orbitofrontal cortex (OFC), insula (IN),
      primary/secondary sensory area (SI/SII), superior temporal cortex (STC),
      precuneus (pCUN) and posterior cingulate cortex (PCC). Meanwhile, significantly
      decreased subcortical volumes of the caudate, thalamus and amygdala were found in
      PDM patients. Moreover, there were significant positive correlations between the
      PDM-related duration and the OFC, SFC, STC and IN. The MPQ scores were positively
      correlated with the pCUN. CONCLUSIONS: These findings provide further evidence
      for grey matter changes in patients with PDM, and in addition, the results
      support relationships between the structural abnormalities and their role in
      symptom production. All these results are likely to be potential valuable to
      provide us with direct information about the neural basis of PDM.

PMID- 26223338
TI  - Evaluation of lead and essential elements in whole blood during pregnancy: a
      cross-sectional study.
AB  - AIM: Physiological concentrations of some elements fluctuate during pregnancy due
      to the increased requirements of growing fetus and changes in the maternal
      physiology. The aim of the study is to evaluate the distribution at different
      stages of pregnancy in healthy Chinese women and to show the association between
      trace elements and gestational age-specific reference intervals. METHODS: A cross
      sectional study was performed in 1089 pregnant women and 677 nonpregnant control
      women. Five element concentrations, including Cu, Zn, Ca, Mg, Pb in the blood
      were determined by atomic absorption spectrometry. Spearman's rank correlation
      test was used to assess the relationship between weeks of gestation and blood
      element concentrations. RESULTS: The mean levels of Cu and Mg were 23.64 +/- 4.69
      MUmol/L and 1.36 +/- 0.12 mmol/L, respectively, in the control women. While 0.68
      % of all pregnant women showed Cu levels below the normal ranges, the levels of
      Mg were comparable in different groups. Though the overall mean blood zinc and Ca
      concentrations (83.84 +/- 17.50 MUmol/L and 1.60 +/- 0.15 mmol/L, respectively)
      increased gradually with the progress of gestation, the Zn and Ca deficiency
      levels (16.6 and 3.6 %, respectively) decreased with the advance of gestation.
      Compared with nonpregnant group, the concentrations of Cu, Zn, Ca, Mg, Pb during
      the different stages of pregnancy, as a whole, were significantly different.
      Positive correlations were observed between weeks of gestation and blood Cu, Ca,
      Pb concentrations (r = 0.301, 0.221, 0.223; P < 0.05). There was a negative
      correlation blood Mg concentrations and weeks of gestation (r = -0.321; P <
      0.05). A weak positive correlation was noted between Zn concentrations and weeks
      of gestation (r = 0.125; P < 0.05). CONCLUSION: The importance of Cu and Mg
      deficiency and supplementation is well realized, but, Zn/Ca deficiency and Pb
      exposure is still exist; the overall deficiency of pregnant women was not so
      optimistic. During pregnancy, the established reference values will provide an
      important guidance for the reasonable supplementation of essential elements and
      surveillance of lead overexposure.

PMID- 26223339
TI  - Effects of peripheral blood mononuclear cells on Haemonchus contortus larval
      motility in vitro.
AB  - The objective of this experiment was to determine effects of peripheral blood
      mononuclear cells (PBMC), derived from parasite-resistant St. Croix (STC) and
      parasite-susceptible Suffolk (SF) sheep, on motility of Haemonchus contortus L3
      stage larvae in vitro. Peripheral blood mononuclear cells were collected from 10
      lambs of each breed, 5 naive and 5 which had received a priming infection with H.
      contortus. Larval motility was quantified using a MIF Nikon Sweptfield microscope
      and NIS Elements AR software, and measurements included path length (PL) (MUm),
      velocity (VEL) (MUm/s) and acceleration (ACC) (MUm/s2 ). After 18 h of
      incubation, PL and VEL were greatest in larvae cultured with SF-derived PMBC and
      were significantly different from all other groups (P < 0.01). No difference was
      observed in PL or VEL between larvae exposed to naive or primed STC-derived PBMC
      and primed-SF PBMC. Differences in ACC were detected between larvae cultured with
      primed STC-derived PBMC (10.91 MUm/s2 ) and naive SF-derived PBMC (45.7 MUm/s2 )
      (P = 0.035). These data indicate an innate ability of STC-derived PBMC to
      severely inhibit larval motility.

PMID- 26223340
TI  - Long-Term Survival is not Impaired After the Complete Resection of Neuroendocrine
      Tumors of the Appendix.
AB  - BACKGROUND: Appendiceal neuroendocrine tumors (aNET) are a common entity in
      routine medical care, with a rate per appendectomy as high as 0.3-0.9 %.
      Considering the relatively young age at diagnosis for these patients, exact
      information about the long-term prognosis of aNET is required. Survival rates
      vary substantially between 71 and 100 % and are mostly limited to 5 years. This
      investigation assessed the long-term mortality rates of patients who underwent
      aNET resections at fifteen hospitals. METHODS: Between 1990 and 2003, the 10-year
      survival rates of 79 patients were analyzed using risk-adjusted Cox proportional
      hazard regression models adjusted for population-based baseline mortality.
      Additionally, prognostic factors for the oncologic outcomes were assessed.
      RESULTS: The median follow-up of all patients was 12.1 and 13.7 years for those
      alive. All patients underwent curative R0 resections. No distant metastases were
      diagnosed. A total of 31 (39.2 %), 29 (36.7 %), 18 (22.8 %), and 1 (1.3 %)
      patients had stage I, IIA, IIB, and IIIB aNET, respectively, according to the
      latest classification by the European Neuroendocrine Tumor Society. The 10-year
      overall and relative survival rates were 83.6 % (95 % CI 75.5-92.6 %) and 96.7 %
      (95 % CI 87.5-107 %), respectively. The 10-year relative survival rate after
      resection of aNET did not differ from the survival of the average national
      population with the same age and gender (p = 0.947). Second primary malignancies
      (hazard ratio of death 7.0, 95 % CI 1.6-30.6) were identified as a significant
      prognosticator for long-term survival. CONCLUSIONS: Long-term survival is not
      significantly depreciated after the curative resection of aNET.

PMID- 26223341
TI  - Is Radical Surgery for Liver Hydatid Cyst the Right Way?

PMID- 26223344
TI  - Obstetrician training associated with better outcomes.

PMID- 26223343
TI  - Circulating annexin A5 predicts mortality in patients with heart failure.
AB  - BACKGROUND: Natriuretic peptides are currently used to predict mortality in
      patients with heart failure (HF). However, novel independent biomarkers are
      needed to improve risk stratification in these patients. We hypothesized that
      annexin A5 (anxA5) would be highly expressed by organs which are generally
      affected by HF and that circulating anxA5 levels would predict mortality in HF
      patients. METHODS: We prospectively determined the diagnostic value of anxA5, N
      terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and
      estimated glomerular filtration rate (eGFR) to predict mortality in 180 HF
      patients during a median follow-up of 3.6 years. Studies were conducted with
      anxA5(-/-) mice to investigate the underlying mechanisms. RESULTS: AnxA5 levels
      were significantly elevated in HF patients compared to healthy control subjects.
      Cox regression analysis demonstrated that anxA5, NT-proBNP and eGFR all predict
      mortality independently. AnxA5 significantly improved the diagnostic efficiency
      of NT-proBNP alone (improvement of c-statistic from 0.662 to 0.705, P < 0.001)
      and also combined with eGFR and CRP (improvement of c-statistic from 0.675 to
      0.738, P < 0.001) to predict mortality in the Cox regression model. Receiver
      operating characteristic curve analysis showed that anxA5 predicted 3-year
      survival (area under curve 0.708) with an optimal cut-off value of 2.24 ng mL(-1)
      . Using anxA5(-/-) mice, we demonstrated that anxA5 is highly expressed in organs
      that are often affected by HF including lung, kidney, liver and spleen. Lysis of
      these organs in vitro resulted in a marked and significant increase in anxA5
      concentrations. CONCLUSION: AnxA5 improves the diagnostic efficiency of
      conventional biomarkers to predict mortality in HF patients. Whereas natriuretic
      peptides originate from the myocardium, high circulating anxA5 levels in patients
      with HF are likely to reflect peripheral organ damage secondary to HF.

PMID- 26223342
TI  - Conserved size and periodicity of pyramidal patches in layer 2 of medial/caudal
      entorhinal cortex.
AB  - To understand the structural basis of grid cell activity, we compare medial
      entorhinal cortex architecture in layer 2 across five mammalian species (Etruscan
      shrews, mice, rats, Egyptian fruit bats, and humans), bridging ~100 million years
      of evolutionary diversity. Principal neurons in layer 2 are divided into two
      distinct cell types, pyramidal and stellate, based on morphology,
      immunoreactivity, and functional properties. We confirm the existence of patches
      of calbindin-positive pyramidal cells across these species, arranged periodically
      according to analyses techniques like spatial autocorrelation, grid scores, and
      modifiable areal unit analysis. In rodents, which show sustained theta
      oscillations in entorhinal cortex, cholinergic innervation targeted calbindin
      patches. In bats and humans, which only show intermittent entorhinal theta
      activity, cholinergic innervation avoided calbindin patches. The organization of
      calbindin-negative and calbindin-positive cells showed marked differences in
      entorhinal subregions of the human brain. Layer 2 of the rodent medial and the
      human caudal entorhinal cortex were structurally similar in that in both species
      patches of calbindin-positive pyramidal cells were superimposed on scattered
      stellate cells. The number of calbindin-positive neurons in a patch increased
      from ~80 in Etruscan shrews to ~800 in humans, only an ~10-fold over a 20,000
      fold difference in brain size. The relatively constant size of calbindin patches
      differs from cortical modules such as barrels, which scale with brain size. Thus,
      selective pressure appears to conserve the distribution of stellate and pyramidal
      cells, periodic arrangement of calbindin patches, and relatively constant neuron
      number in calbindin patches in medial/caudal entorhinal cortex.

PMID- 26223345
TI  - Randomized, controlled trial of entecavir versus placebo in children with
      hepatitis B envelope antigen-positive chronic hepatitis B.
AB  - This ongoing, randomized phase III study assesses the safety and efficacy of
      entecavir versus placebo in nucleos(t)ide-naive children (2 to <18 years) with
      hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B (CHB). Blinded
      treatment was administered for a minimum of 48 weeks. After week 48, patients
      with HBeAg seroconversion continued blinded treatment; those without switched to
      open-label entecavir. The primary endpoint was HBeAg seroconversion and HBV DNA
      <50 IU/mL at week 48. A total of 180 patients were randomized (2:1) and treated.
      Baseline median age was 12 years, with approximately 50% of children ages >12 to
      <18, and 25% each ages >=2 to <=6 and >6 to <=12. Rates for the primary endpoint
      at week 48 were significantly higher with entecavir than placebo (24.2% [29 of
      120] vs. 3.3% [2 of 60]; P = 0.0008). Furthermore, higher response rates were
      observed with entecavir compared with placebo for the key week 48 secondary
      endpoints: HBV DNA <50 IU/mL (49.2% [59 of 120] vs. 3.3% [2 of 60]; P < 0.0001);
      alanine aminotransferase normalization (67.5% [81 of 120] vs. 23.3% [14 of 60]; P
      < 0.0001); and HBeAg seroconversion (24.2% [29 of 120] vs. 10.0% [6 of 60]; P =
      0.0210). Among entecavir-randomized patients, there was an increase in all
      efficacy endpoints between weeks 48 and 96, including an increase from 49% to 64%
      in virological suppression. The cumulative probability of emergent entecavir
      resistance through years 1 and 2 of entecavir was 0.6% and 2.6%, respectively.
      Entecavir was well tolerated with no observed differences in adverse events or
      changes in growth compared with placebo. CONCLUSION: In childhood CHB, entecavir
      demonstrated superior antiviral efficacy to placebo with a favorable safety
      profile. These results support the use of entecavir as a therapeutic option in
      children and adolescents with CHB.

PMID- 26223346
TI  - Association between pre hemodialysis serum sodium concentration and blood
      pressure: results from a retrospective analysis from the international monitoring
      dialysis outcomes (MONDO) initiative.
AB  - A recent study from the United Kingdom indicates an association between pre
      hemodialysis (HD) serum sodium (SNa(+)) and systolic and diastolic blood pressure
      (SBP and DBP) in chronic HD patients. We extend this analysis to an international
      cohort of incident HD patients. The Monitoring Dialysis Outcomes initiative
      encompasses patients from 41 countries. Over 2 years monthly pre-HD SNa(+) levels
      were used as predictors of pre-HD SBP and DBP in a linear mixed model (LMM)
      adjusted for age, gender, interdialytic weight gain, diabetes, serum albumin and
      calcium. Similar models were constructed with DBP as outcome. Analyses were
      carried out stratified by continent (North and South America; Europe and Asia).
      LMMs were also constructed for the entire observation period of 2 years, and
      separately the first and the second year after HD initiation. We studied 17 050
      incident patients and found SNa(+) to have a significant slope estimate in the
      LMM predicting pre-HD SBP and DBP (ranging from 0.22 to 0.29 and 0.10 to 0.21 mm
      Hg per mEq l(-1), respectively, between the continents). The findings were
      similar in subsets of SBP and SNa(+) tertiles, and separately analyzed for the
      first and second year. Our analysis shows an independent association between SNa,
      SBP and DBP in a large intercontinental database, indicating that this relation
      is a profound biological phenomenon in incident and prevalent HD patients,
      generalizable to an international level and independent of SBP and DBP magnitude.

PMID- 26223347
TI  - Relationship between blood pressure variability and renal activity of the renin
      angiotensin system.
AB  - Local renin-angiotensin system (RAS) activity in the kidneys is a pathogenetic
      factor in patients with primary hypertension. This study aimed to determine the
      relationship between local kidney RAS activity and blood pressure variability, as
      the literature currently lacks any such study. The study included 73 consecutive
      primary hypertensive patients. All patients underwent 24-h ambulatory blood
      pressure monitoring to determine the average real variability (ARV) index, as an
      indicator of blood pressure variability. Local RAS activity was determined using
      the urine angiotensinogen/creatinine (UAGT/UCre) ratio. The high UAGT/UCre ratio
      group had significantly higher mean 24-h systolic ARV than the low UAGT/UCre
      ratio group (13.2+/-3.4 vs 11.0+/-2.6, P=0.003). Similarly, the high UAGT/UCre
      ratio group had significantly higher mean 24-h diastolic ARV than the low
      UAGT/UCre ratio group (10.8+/-3.2 vs 8.7+/-2.2, P=0.001). Multivariate regression
      analysis showed that Log(UAGT/UCre) was an independent predictor of both 24-h
      diastolic ARV and 24-h systolic ARV. Local RAS activity in the kidneys might have
      a role in blood pressure variability. On the basis of these findings, we think
      that additional prospective studies are needed to more fully discern the effect
      of local RAS activity on blood pressure variability. 

PMID- 26223348
TI  - Differential peptidomics assessment of strain and age differences in mice in
      response to acute cocaine administration.
AB  - Neurochemical differences in the hypothalamic-pituitary axis between individuals
      and between ages may contribute to differential susceptibility to cocaine abuse.
      This study measured peptide levels in the pituitary gland (Pit) and lateral
      hypothalamus (LH) in adolescent (age 30 days) and adult (age 65 days) mice from
      four standard inbred strains, FVB/NJ, DBA/2J, C57BL/6J, and BALB/cByJ, which have
      previously been characterized for acute locomotor responses to cocaine.
      Individual peptide profiles were analyzed using mass spectrometric profiling and
      principal component analysis. Sequences of assigned peptides were verified by
      tandem mass spectrometry. Principal component analysis classified all strains
      according to their distinct peptide profiles in Pit samples from adolescent mice,
      but not adults. Select pro-opiomelanocortin-derived peptides were significantly
      higher in adolescent BALB/cByJ and DBA/2J mice than in FVB/NJ or C57BL/6J mice. A
      subset of peptides in the LH, but not in the Pit, was altered by cocaine in
      adolescents. A 15 mg/kg dose of cocaine induced greater peptide alterations than
      a 30 mg/kg dose, particularly in FVB/NJ animals, with larger differences in
      adolescents than adults. Neuropeptides in the LH affected by acute cocaine
      administration included pro-opiomelanocortin-, myelin basic protein-, and
      glutamate transporter-derived peptides. The observed peptide differences could
      contribute to differential behavioral sensitivity to cocaine among strains and
      ages. Peptides were measured using mass spectrometry (MALDI-TOF) in individual
      lateral hypothalamus and pituitary samples from four strains and two ages of
      inbred mice in response to acute cocaine administration. Principal component
      analyses (PCA) classified the strains according to their peptide profiles from
      adolescent mice, and a subset of peptides in the lateral hypothalamus was altered
      by cocaine in adolescents.

PMID- 26223350
TI  - Ipsilateral radiotherapy for squamous cell carcinoma of the tonsil.
AB  - The purpose of this study is to update our institution's experience with
      ipsilateral radiation therapy (RT) for squamous cell carcinoma of the tonsillar
      area. Outcome study of 76 patients treated between 1984 and 2012 with ipsilateral
      RT for squamous cell carcinoma of the tonsil. Patients had either cT1 (n = 41, 54
      %) or cT2 (n = 35, 46 %) primaries and cN0 (n = 27, 36 %), cN1 (n = 15, 20 %),
      cN2a (n = 8, 11 %), or cN2b (n = 26, 34 %) nodal disease. Of these, 32 (42 %)
      patients underwent a planned neck dissection and 21 (28 %) patients received
      concomitant chemotherapy. Median follow-up for all patients was 7.1 years (range
      0.1-27.2) and 7.8 years (range 2.1-27.2 years) for living patients. The 2- and 5
      year control and survival rates were as follows: local control, 98.6 and 96.9 %;
      local-regional control 95.8 and 92.6 %; cause-specific survival 95.9 and 93.1 %;
      and overall survival, 92.1 and 83.8 %. One patient failed in the contralateral,
      non-radiated neck 3 years after primary treatment. Univariate analysis revealed
      that overall survival was significantly influenced by whether the patient had a
      primary tumor in the anterior tonsillar pillar versus the tonsillar fossa with
      the latter performing better. The incidence of severe late complications was 16
      %. Ipsilateral RT for patients with squamous cell carcinoma of the anterior
      tonsillar pillar or tonsillar fossa with no base of tongue or soft palate
      extension is an efficacious treatment that provides excellent control rates with
      a relatively low incidence of late complications. 

PMID- 26223349
TI  - Effects of chronic alcohol consumption on neuronal function in the non-human
      primate BNST.
AB  - Alterations in hypothalamic-pituitary-adrenal axis function contribute to many of
      the adverse behavioral effects of chronic voluntary alcohol drinking, including
      alcohol dependence and mood disorders; limbic brain structures such as the bed
      nucleus of the stria terminalis (BNST) may be key sites for these effects. Here,
      we measured circulating levels of several steroid hormones and performed whole
      cell electrophysiological recordings from acutely prepared BNST slices of male
      rhesus monkeys allowed to self-administer alcohol for 12 months or a control
      solution. Initial comparisons revealed that BNST neurons in alcohol-drinking
      monkeys had decreased membrane resistance, increased frequency of spontaneous
      inhibitory postsynaptic currents (sIPSCs) with no change in spontaneous
      excitatory postsynaptic currents (sEPSCs). We then used a combined variable
      cluster analysis and linear mixed model statistical approach to determine whether
      specific factors including stress and sex hormones, age and measures of alcohol
      consumption and intoxication are related to these BNST measures. Modeling results
      showed that specific measures of alcohol consumption and stress-related hormone
      levels predicted differences in membrane conductance in BNST neurons. Distinct
      groups of adrenal stress hormones were negatively associated with the frequency
      of sIPSCs and sEPSCs, and alcohol drinking measures and basal neuronal membrane
      properties were additional positive predictors of inhibitory, but not excitatory,
      PSCs. The amplitude of sEPSCs was highly positively correlated with age,
      independent of other variables. Together, these results suggest that chronic
      voluntary alcohol consumption strongly influences limbic function in non-human
      primates, potentially via interactions with or modulation by other physiological
      variables, including stress steroid hormones and age.

PMID- 26223351
TI  - The endoscopic study of human middle ear mucociliary transport.
AB  - The mucociliary clearance (MCC) is an important defence mechanism of the middle
      ear. The mucociliary transport (MCT) is a part of MCC. We measured the duration
      of MCT and visualised its routes in middle ears of 31 patients (mean age 45
      years; range 7-61 years; SD 11.6) with intact tympanic membrane, with ventilated
      middle ears and without a history of prolonged otitis media. The transition time
      of indigo carmine dye from the promontory mucosa to the middle ear orifice of the
      Eustachian tube (ET) was observed with a rigid 30 degrees , 1.7-mm-diameter
      tympanoscope. The dye took an average of 7 min (range 4.5-15 min; SD 3.4; median
      4.5) to reach the ET orifice in 25 (81 %) patients. Three main ciliary pathways
      were detected: (1) below and parallel to the tensor tympani muscle; (2)
      downwards, anterior to the round window, and then ascending to the ET; and (3)
      straight across the promontory. 

PMID- 26223352
TI  - The contralateral ear in cholesteatoma.
AB  - Middle ear cholesteatoma has been extensively studied. Theories of cholesteatoma
      pathogenesis involving previous tympanic membrane retraction are the most widely
      accepted, but the contralateral ear in patients with cholesteatoma remains
      unstudied. This study aimed to investigate the contralateral ear in patients with
      cholesteatoma, and to determine whether the characteristics of it differ
      according to patient age and cholesteatoma growth patterns. This study was cross
      sectional. We evaluated 356 patients with middle ear cholesteatoma in at least
      one ear, and no history of surgery, between August 2000 and March 2013.
      Otoendoscopy was conducted on both the affected and the contralateral ear. They
      were classified as normal, tympanic membrane perforation, moderate to severe
      tympanic membrane retraction and cholesteatoma. The mean age of the patients was
      32.77 years, and 53.1 % of the cohort were female. Only 34.8 % of the
      contralateral ears were normal. The most common abnormality was moderate to
      severe tympanic membrane retraction (41.6 %). Cholesteatoma was identified in 16
      %. Children exhibited a greater frequency of tympanic membrane retractions,
      whereas adults exhibited a greater frequency of cholesteatoma. All of the
      contralateral ears in the anterior epitympanic group were normal, but otherwise
      there were no differences in the contralateral ear when we compared the
      cholesteatoma growth patterns. We conclude that patients diagnosed with acquired
      cholesteatoma of one ear are significantly more likely to exhibit abnormalities
      of the contralateral ear. 

PMID- 26223353
TI  - Computer-aided transrectal ultrasound: does prostate HistoScanningTM improve
      detection performance of prostate cancer in repeat biopsies?
AB  - BACKGROUND: An imaging tool providing reliable prostate cancer (PCa) detection
      and localization is necessary to improve common diagnostic pathway with
      ultrasound targeted biopsies. To determine the performance of transrectal
      ultrasound (TRUS) augmented by prostate HistoScanning(TM) analysis (PHS) we
      investigated the detection of prostate cancer (PCa) foci in repeat prostate
      biopsies (Bx). METHODS: 97 men with a mean age of 66.2 (44-82) years underwent
      PHS augmented TRUS analysis prior to a repeat Bx. Three PHS positive foci were
      defined in accordance with 6 bilateral prostatic sectors. Targeted Bx (tBx)
      limited to PHS positive foci and a systematic 14-core backup Bx (sBx) were taken.
      Results were correlated to biopsy outcome. Sensitivity, specificity, predictive
      accuracy, negative predictive value (NPV) and positive predictive value (PPV)
      were calculated. RESULTS: PCa was found in 31 of 97 (32%) patients. Detection
      rate in tBx was significantly higher (p < .001). Detection rate in tBx and sBx
      did not differ on patient level (p >= 0.7). PHS sensitivity, specificity,
      predictive accuracy, PPV and NPV were 45%, 83%, 80%, 19% and 95%, respectively.
      CONCLUSIONS: PHS augmented TRUS identifies abnormal prostatic tissue. Although
      sensitivity and PPV for PCa are low, PHS information facilitates Bx targeting to
      vulnerable foci and results in a higher cancer detection rate. PHS targeted Bx
      should be considered in patients at persistent risk of PCa.

PMID- 26223354
TI  - A functional genetic variant in fragile-site gene FATS modulates the risk of
      breast cancer in triparous women.
AB  - BACKGROUND: The fragile-site associated tumor suppressor (FATS, formerly known as
      C10orf90), a regulator of p53-p21 pathway has been involved in the onset of
      breast cancer. Recent data support the idea that the crosstalk between FATS and
      p53 may be of physiological importance for reproduction during evolution. The aim
      of the current study was to test the hypothesis that FATS genetic polymorphism
      can influence the risk of breast cancer. METHODS: We conducted population-based
      studies in two independent cohorts comprising 1 532 cases and 1 573 controls in
      Tianjin of North China, and 804 cases and 835 controls in Guangzhou of South
      China, coupled with functional validation methods, to investigate the role of
      FATS genetic variant in breast cancer risk. RESULTS: We identified a functional
      variant rs11245007 (905C > T, 262D/N) in fragile-site gene FATS that modulates
      p53 activation. FATS-262 N exhibited stronger E3 activity to polyubiquitinate p53
      than did FATS-262D, leading to the stronger transcriptional activity of p53 and
      more pronounced stabilization of p53 protein and its activation in response to
      DNA damage. Case-control studies found that CT or TT genotype was significantly
      associated with a protective effect on breast cancer risk in women with parity >=
      3, which was not affected by family history. CONCLUSIONS: Our findings suggest
      the role of FATS-p53 signaling cascade in suppressing pregnancy-related
      carcinogenesis and potential application of FATS genotyping in breast cancer
      prevention.

PMID- 26223355
TI  - Are biological agents toxic to human chondrocytes and osteocytes?
AB  - PURPOSE: The aim of the present study is to investigate the effects of biological
      agents (BAs) on human chondrocytes and osteocytes in vitro. METHODS: Primary cell
      cultures obtained from gonarthrosis patients were divided into four groups, two
      of which were designated as control cultures of chondrocyte and osteocyte, and
      the other two groups were exposed to BAs administered via the culture medium.
      Cultured cells were characterized by immunophenotyping. Before and after
      administration of the agents, the cultures were observed by inverted and
      environmental scanning electron microscopy (ESEM). The number of live cells and
      the proliferation rate were monitored by MTT assay. RESULTS: Rituximab and
      adalimumab were the least toxic agents to chondrocytes, whereas adalimumab and
      etanercept were to osteocytes. CONCLUSION: During periods of intense active
      inflammation, the concentration of the preferred BAs after inhibition of
      inflammation needs to be emphasized when their effects on cartilage and bone
      tissue are considered at the cellular level if the clinical practice is to
      continue.

PMID- 26223357
TI  - Maternally transferred dioxin-like compounds can affect the reproductive success
      of European eel.
AB  - Reported concentrations of dioxin-like compounds accumulated in the European eel
      (Anguilla anguilla) were used to perform a risk assessment for eel larval
      survival, taking into account a modeled amplification of tissue concentrations
      with a factor of 1.33 during spawning migration. The calculated concentrations of
      dioxin-like compounds finally deposited in the eggs were compared with the
      internal effect concentrations for survival of early life stages of the European
      eel; these concentrations, by lack of experimental data, were estimated from a
      sensitivity distribution based on literature data by assuming that eel larvae are
      among the 10% most sensitive teleost fish species. Given concentrations of dioxin
      like contaminants and assuming a relatively high sensitivity, it can be expected
      that larvae from eggs produced by eel from highly contaminated locations in
      Europe will experience increased mortality as a result of maternally transferred
      dioxin-like contaminants. As historical persistent organic pollutant
      concentrations in eel tissue were higher, this impact must have been stronger in
      the past. Potential effects of other compounds or effects on the migration,
      condition, and fertility of the parental animals were not taken into account. It
      is important to further study the overall impact of contaminants on the
      reproductive success of the European eel as this may have been underestimated
      until now.

PMID- 26223356
TI  - Leukocyte presence does not increase microbicidal activity of Platelet-rich
      Plasma in vitro.
AB  - BACKGROUND: Human platelets are a rich reservoir of molecules that promote
      regenerative processes and microbicidal activity. This activity might be
      increased by concentration in platelet-rich plasma (PRP) products and modulated
      by the presence of leukocytes. Despite extensive use in clinical procedures, only
      few studies have investigated PRP's real microbicidal potential. Therefore, this
      study aimed at comparing the in vitro microbicidal activity of platelets and
      leukocyte-enriched PRP (L-PRP) to pure platelet-rich plasma (P-PRP) and the
      contribution of leukocytes to microbicidal properties. Antimicrobial effects of P
      and L-PRP were tested against Escherichia Coli, Staphylococcus Aureus,
      Klebsiella Pneumoniae, Pseudomonas Aeruginosa and Enterococcus Faecalis.
      Furthermore, L-PRP was frozen (L-PRP cryo) to assess whether the preparation
      maintained in vitro characteristics. Microbicidal proteins released by the three
      preparations were also evaluated. RESULTS: L-PRP, L-PRP cryo and P-PRP generally
      induced comparable bacterial growth inhibition for up to 4 h' incubation, range 1
      4 log. MIP-1alpha, RANTES, GRO-alpha, IL-8, NAP-2, SDF-1alpha and IL-6 showed
      strong microbicidal potential. CONCLUSIONS: We found in vitro antibacterial
      activity of L-PRP and P-PRP and the possibility to cryopreserve L-PRP, without
      important changes to its effectiveness; similar microbicidal activity between
      preparations containing or not leukocytes; and the contribution of three new
      molecules (NAP-2, SDF-1alpha and IL-6).

PMID- 26223358
TI  - Erratum to: Biosynthesis of caffeic acid in Escherichia coli using its endogenous
      hydroxylase complex.

PMID- 26223360
TI  - Should Health Care Providers Uphold the DNR of a Terminally Ill Patient Who
      Attempts Suicide?
AB  - An individual's right to refuse life-sustaining treatment is a fundamental
      expression of patient autonomy; however, supporting this right poses ethical
      dilemmas for healthcare providers when the patient has attempted suicide.
      Emergency physicians encounter patients who have attempted suicide and are likely
      among the first medical providers to face the dilemma of honoring the patient's
      DNR or intervening to reverse the effects of potentially fatal actions. We
      illustrate this issue by introducing a case example in which the DNR of a
      terminally ill woman was not honored because the cause of her cardiac arrest was
      suicide. We argue that although a terminal diagnosis should change the way health
      care providers respond to a suicide attempt, many of the theoretical
      underpinnings for how one should treat suicide attempts-especially the criterion
      of external reasonability, that is the action to withhold or withdraw life
      sustaining measures is reasonable independent of the precipitating event-are
      common to all situations (Brown et al. in Am J Bioeth 13(3):3-12, 2013). The
      presumption that patients who attempt suicide lack capacity due to acute mental
      illness is flawed because it fails to account for a competent individual's
      reasonable preference to not be forced to live in an unbearable, terminal
      condition. In states without legislation allowing physician aid in dying,
      patients and providers must grapple with these limitations on a case-by-case
      basis. In cases where the patient has a limited life expectancy and there is not
      concern for psychiatric illness as the primary cause of the suicidal action, we
      argue that the negative right to refuse life-sustaining treatment should prevail.

PMID- 26223359
TI  - Neutrophil to lymphocyte ratio (NLR) improves the risk assessment of ISS staging
      in newly diagnosed MM patients treated upfront with novel agents.
AB  - Recent reports identify the ratio between absolute neutrophil count (ANC) and
      absolute lymphocyte count (ALC), called neutrophil to lymphocyte ratio (NLR), as
      a predictor of progression-free survival (PFS) and overall survival (OS) in
      various malignancies. We retrospectively examined the NLR in a cohort of 309
      newly diagnosed multiple myeloma (MM) patients treated upfront with novel agents.
      NLR was calculated using data obtained from the complete blood count (CBC) at
      diagnosis and subsequently correlated with PFS and OS. The median NLR was 1.9
      (range 0.4-15.9). Higher NLR was independent of international staging system
      (ISS) stage, plasma cell infiltration or cytogenetics. The 5-year PFS and OS
      estimates were, respectively, 18.2 and 36.4 % for patients with NLR >= 2 versus
      25.5 and 66.6 % in patients with NLR < 2. Among younger patients (age <65 years,
      N = 179), NLR >= 2 had a negative prognostic impact on both PFS and OS, in all
      ISS stages. By combining ISS stage and NLR in a model limited to young patients,
      we found that 19 % of the patients were classified as very low risk, 70 %
      standard risk and 11 % very high risk. The 5-year estimates were 39.3, 19.4 and
      10.9 % for PFS and 95.8, 50.9 and 23.6 % for OS for very low, standard-risk and
      very high-risk groups. We found NLR to be a predictor of PFS and OS in MM
      patients treated upfront with novel agents. NLR can be combined with ISS staging
      system to identify patients with dismal outcome. However, larger cohorts and
      prospective studies are needed to use NLR as additional parameter to personalise
      MM therapy in the era of novel agents. 

PMID- 26223361
TI  - Results of a large retrospective analysis of the effect of intended dose
      intensity of R-CHOP on outcome in a cohort of consecutive, unselected elderly
      patients with de novo diffuse large B cell lymphoma.

PMID- 26223363
TI  - Diabetes-related nutrition knowledge and dietary intake among adults with type 2
      diabetes.

PMID- 26223362
TI  - Immature spinal cord neurons are dynamic regulators of adult nociceptive
      sensitivity.
AB  - Chronic pain is a debilitating condition with unknown mechanism. Nociceptive
      sensitivity may be regulated by genetic factors, some of which have been
      separately linked to neuronal progenitor cells and neuronal differentiation. This
      suggests that genetic factors that interfere with neuronal differentiation may
      contribute to a chronic increase in nociceptive sensitivity, by extending the
      immature, hyperexcitable stage of spinal cord neurons. Although adult rodent
      spinal cord neurogenesis was previously demonstrated, the fate of these
      progenitor cells is unknown. Here, we show that peripheral nerve injury in adult
      rats induces extensive spinal cord neurogenesis and a long-term increase in the
      number of spinal cord laminae I-II neurons ipsilateral to injury. The production
      and maturation of these new neurons correlates with the time course and
      modulation of nociceptive behaviour, and transiently mimics the cellular and
      behavioural conditions present in genetically modified animal models of chronic
      pain. This suggests that the number of immature neurons present at any time in
      the spinal cord dorsal horns contributes to the regulation of nociceptive
      sensitivity. The continuous turnover of these neurons, which can fluctuate
      between normal and injured states, is a dynamic regulator of nociceptive
      sensitivity. In support of this hypothesis, we find that promoters of neuronal
      differentiation inhibit, while promoters of neurogenesis increase long-term
      nociception. TrkB agonists, well-known promoters of nociception in the short
      term, significantly inhibit long-term nociception by promoting the
      differentiation of newly produced immature neurons. These findings suggest that
      promoters of neuronal differentiation may be used to alleviate chronic pain. 

PMID- 26223364
TI  - Hysteroscopy prior to repeat embryo transfer may improve pregnancy outcomes for
      asymptomatic women with repeated implantation failure.
AB  - AIM: The aim of this study was to evaluate the efficacy of hysteroscopy (HS) in
      detecting intrauterine abnormalities prior to repeat embryo transfer and
      improving pregnancy outcomes in asymptomatic women with repeated implantation
      failure (RIF). MATERIAL AND METHODS: A prospective cohort study was conducted
      involving 672 asymptomatic RIF women from a Chinese university hospital.
      Pregnancy outcomes between the HS (subdivided into patients with and without
      intrauterine abnormalities) and non-HS groups were compared. RESULTS: The
      incidence of intrauterine abnormalities in the HS group was 37.13%. The most
      common abnormalities included endometrial polyps or polypoid endometrium,
      endometrial hyperplasia and intrauterine adhesions. Clinical pregnancy and
      implantation rates in the HS group were significantly higher than in the non-HS
      group (41.92% vs 32.25%; 23.82% vs 18.60%, respectively). There were no
      significant differences in early abortion, ectopic pregnancy, late abortion and
      live birth rates. The clinical pregnancy and implantation rates in both HS
      subgroups were significantly higher when compared to the non-HS group, whereas
      there were no significant differences between the subgroups. CONCLUSION: HS
      improved pregnancy outcomes in women with or without intrauterine abnormalities.
      HS may be routinely performed before repeat embryo transfer in RIF women.

PMID- 26223365
TI  - Termination of pregnancy for fetal abnormalities: main arguments and a decision
      tree model.
AB  - INTRODUCTION: By looking through our ethical committee cases, we demonstrate the
      main arguments we use for making a judgment in face of fetal abnormalities. Our
      decision making model is a simplified algorithm of the arguments and concepts we
      use in scientific-ethic discussion. MATERIALS AND METHODS: A retrospective
      analysis was conducted from single, tertiary referral center of patients
      evaluated for fetal abnormalities from 2004 to 2014. We hypothesized that all our
      judgments would fit into a decision-tree model. RESULTS: 553 fetal abnormality
      cases were discussed, 348 (63%) were given termination of pregnancy (TOP)
      proposal. When detected <24 weeks, fetuses with chromosomal abnormality/genetic
      disorders (n:100) and with mental retardation risk (n:93) ended up with TOP
      proposal. For incompatibility with life cases (n:111) and the multimorbidity
      cases (n:44) the committee suggest TOP, regardless of gestational age. The
      highest family approval ratios were in chromosomal abnormalities/genetic
      disorders group (93%), and the lowest figures were in mental retardation risk
      group (80%). DISCUSSION: Continuously changing literature on prenatal and
      postnatal therapy options and the long term outcome of various fetal
      abnormalities influence committee decisions. Theoretical high success rates and
      inconsistent data on long term prognosis of some anomaly groups resulted in
      heterogenous decisions and various approval ratios.

PMID- 26223366
TI  - Strychnine as Target, Samarium Diiodide as Tool: A Personal Story.
AB  - Strychnine stands out from the group of classical natural products as one of the
      first complex compounds to be isolated in pure form and an extreme challenge to
      be structurally characterized. It has played a central role in natural product
      total syntheses and the surge in the development of innovative synthetic methods
      for many decades. Recently, we have accomplished one of the shortest formal total
      syntheses of strychnine (in ten steps and 14% overall yield or even shorter in
      eight steps and 10% overall yield). The evolution of a productive synthetic
      strategy, as well as the synthetic challenges tackled, are described here in
      detail, including examples of related transformations. The successful synthetic
      strategy was inspired by the premise that the core structure could be derived
      from simple aromatic indole precursors by a reductive SmI2 -induced ketyl-aryl
      coupling. Other key reactions included a diastereoselective reduction and a
      regioselective elimination protocol. Altogether one of the shortest syntheses of
      iso-strychnine and hence of strychnine was established. 

PMID- 26223367
TI  - Flexible Linker Modulates Glycosaminoglycan Affinity of Decorin Binding Protein
      A.
AB  - Decorin binding protein A (DBPA) is a glycosaminoglycan (GAG)-binding adhesin
      found on the surface of the bacterium Borrelia burgdorferi (B. burgdorferi), the
      causative agent of Lyme disease. DBPA facilitates bacterial adherence to
      extracellular matrices of human tissues and is crucial during the early stage of
      the infection process. Interestingly, DBPA from different strains (B31, N40, and
      PBr) show significant differences in GAG affinities, but the structural basis for
      the differences is not clear. In this study, we show that GAG affinity of N40
      DBPA is modulated in part by flexible segments that control access to the GAG
      binding site, such that shortening of the linker leads to higher GAG affinity
      when analyzed using ELISA, gel mobility shift assay, solution NMR, and isothermal
      titration calorimetry. Our observation that GAG affinity differences among
      different B. burgdorferi strains can be attributed to a flexible linker domain
      regulating access to the GAG-binding domain is novel. It also provides a rare
      example of how neutral amino acids and dynamic segments in GAG binding proteins
      can have a large influence on GAG affinity and provides insights into why the
      number of basic amino acids in the GAG-binding site may not be the only factor
      determining GAG affinity of proteins. 

PMID- 26223368
TI  - Exclusive olive oil consumption has a protective effect on coronary artery
      disease; overview of the THISEAS study.
AB  - OBJECTIVE: The aims of the current report are to present the demographic
      characteristics, clinical characteristics/biochemical indices and lifestyle
      habits of the population and to explore the potential association of exclusive
      olive oil consumption, in relation to lifestyle factors, with coronary artery
      disease risk. DESIGN: Demographic, lifestyle, dietary and biochemical variables
      were recorded. Logistic regression analysis was performed in order to estimate
      the relative risks of developing coronary artery disease. SETTING: The Hellenic
      study of Interactions between Single nucleotide polymorphisms and Eating in
      Atherosclerosis Susceptibility (THISEAS), a medical centre-based case-control
      study conducted in Greek adults. SUBJECTS: We consecutively enrolled 1221 adult
      patients with coronary artery disease and 1344 adult controls. RESULTS: A higher
      prevalence of the conventional established risk factors was observed in cases
      than in controls. Physical activity level was higher in controls (1.4 (sd 0.2)
      than in cases (1.3 (sd 0.3); P<0.001). Regarding current and ex-smokers, the case
      group reported almost double the pack-years of the control group (54.6 (sd 42.8)
      v. 28.3 (sd 26.3), respectively; P<0.001). Exclusive olive oil consumption was
      associated with 37 % lower likelihood of developing coronary artery disease, even
      after taking into account adherence to the Mediterranean diet (OR=0.63; 95 % CI
      0.42, 0.93; P=0.02). CONCLUSIONS: Exclusive olive oil consumption was associated
      with lower risk of coronary artery disease, even after adjusting for adoption of
      an overall healthy dietary pattern such as the Mediterranean diet.

PMID- 26223369
TI  - Phase and redox shifted four iron/four sulfur clusters: fluorous analogs of
      metalloenzyme cofactors.
AB  - Reactions of (1) [Q]2[Fe4S4(SC(CH3)3)4] and the fluorous thiols HS(CH2)nRf8 (n =
      2, 3; Rf8 = (CF2)7CF3)), or (2) [Na]2[Fe4S4(S(CH2)nRf8)4] (n = 2, 3) and
      [PhCH2P((CH2)3Rf6)3][Br] or [PPN][Cl] (PPN = Ph3P[horiz bar, triple dot
      above]N[horiz bar, triple dot above]PPh3), give the title compounds
      [Q]2[Fe4S4(S(CH2)nRf8)4], comprised of a fluorous dianion and in some cases
      fluorous cations, with (1) Q/n = Ph4P/2 (, 67%), Ph4P/3 (, 67%), Me4N/3 (69%),
      and Ph3P(CH2)2Rf6/2 (73%) or (2) PhCH2P((CH2)3Rf6)3/2 (, 39%),
      PhCH2P((CH2)3Rf6)3/3 (, 63%), and PPN/2 (36%). The educt
      [Ph3P(CH2)2Rf6]2[Fe4S4(SC(CH3)3)4] is in turn prepared from FeCl3,
      HSC(CH3)3/CH3ONa, and [Ph3P(CH2)2Rf6][I], and the educts
      [Na]2[Fe4S4(S(CH2)nRf8)4] from [Na]2[Fe4S4(SC(CH3)3)4] and HS(CH2)nRf8. The
      SCH2(1)H and (13)C NMR signals of these paramagnetic salts appear 8.7-10.3 and
      32.3-34.9 ppm downfield from those of the corresponding thiols, but the chemical
      shifts of other signals are nearly normal. The UV-visible spectra show bands
      similar to those of non-fluorous analogs (290-298 nm and 406-415 nm; epsilon = 25
      700 and 19 200 M(-1) cm(-1) for ). The singly fluorous salts are soluble in
      organic solvents of moderate polarity, but not in fluorous solvents. The doubly
      fluorous salts , are soluble in all fluorous solvents assayed, with partition
      coefficients of >99.65 : <0.35 (CF3C6F11/toluene) and 93.2-93.1 : 6.9-6.8 (FC
      72/THF). Cyclic voltammograms carried out using a platinum working microelectrode
      show that is 0.08 V thermodynamically easier to reduce than . 

PMID- 26223370
TI  - Dietary-flavonoid-rich flowers of Rumex nervosus Vahl: Liquid chromatography with
      electrospray ionization tandem mass spectrometry profiling and in vitro anti
      inflammatory effects.
AB  - Rumex nervosus is a plant species found widely in Eastern Africa and the Arabian
      Peninsula. In addition to its uses in traditional medicinal, the plant shows
      various biological activities, such as antiviral, antibacterial, and antioxidant
      activity. In this study, nine flavonols, six flavones, three flavanones, and one
      flavanol were characterized from the flowers of R. nervosus using liquid
      chromatography with electrospray ionization tandem mass spectrometry and
      literature data. Validation data indicated that the determination coefficients
      (R(2) ) were >= 0.9914. The limits of detection and quantification were in the
      ranges of 0.15-1.24 and 0.50-4.13 mg/L, respectively. Recoveries at 10 and 50
      mg/L were 71.1-110.2 and 65.4-115.1%, with relative standard deviations of 7.4
      40.1 and 2.1-13.0%, respectively. Quercetin 3-O-rhamnoside (10) was the dominant
      component, contributing 30.8% of total flavonoids (1003.0 +/- 26.2 mg/kg fresh
      flower sample), whereas luteolin 6-C-glucoside (3) was the lowest yielding
      compound (0.1%). The 19 flavonoids identified were characterized for the first
      time. In vitro anti-inflammatory studies showed that this mixture can suppress
      the production of inflammatory mediators, including inducible nitric oxide
      synthase, cyclooxygenase-2, kappa B inhibitor, and interleukin-1beta, by down
      regulating the nuclear factor-kappa B and mitogen-activated protein kinases
      pathways. The results of this study may provide information for processing R.
      nervosus as a potential source of functional food. 

PMID- 26223371
TI  - Quantitative MR Imaging of Brain Tissue and Brain Pathologies.
AB  - Measurement of basic quantitative magnetic resonance (MR) parameters (e.g.,
      relaxation times T1, T2*, T2 or respective rates R (1/T)) corrected for
      radiofrequency (RF) coil bias yields different conventional and new tissue
      contrasts as well as volumes for tissue segmentation. This approach also provides
      quantitative measures of microstructural and functional tissue changes. We herein
      demonstrate some prospects of quantitative MR imaging in neurological diagnostics
      and science.

PMID- 26223372
TI  - Constructing sequence-dependent protein models using coevolutionary information.
AB  - Recent developments in global statistical methodologies have advanced the
      analysis of large collections of protein sequences for coevolutionary
      information. Coevolution between amino acids in a protein arises from
      compensatory mutations that are needed to maintain the stability or function of a
      protein over the course of evolution. This gives rise to quantifiable
      correlations between amino acid sites within the multiple sequence alignment of a
      protein family. Here, we use the maximum entropy-based approach called mean field
      Direct Coupling Analysis (mfDCA) to infer a Potts model Hamiltonian governing the
      correlated mutations in a protein family. We use the inferred pairwise
      statistical couplings to generate the sequence-dependent heterogeneous
      interaction energies of a structure-based model (SBM) where only native contacts
      are considered. Considering the ribosomal S6 protein and its circular permutants
      as well as the SH3 protein, we demonstrate that these models quantitatively agree
      with experimental data on folding mechanisms. This work serves as a new framework
      for generating coevolutionary data-enriched models that can potentially be used
      to engineer key functional motions and novel interactions in protein systems.

PMID- 26223373
TI  - A2E and lipofuscin distributions in macaque retinal pigment epithelium are
      similar to human.
AB  - The accumulation of lipofuscin, an autofluorescent aging marker, in the retinal
      pigment epithelium (RPE) has been implicated in the development of age-related
      macular degeneration (AMD). Lipofuscin contains several visual cycle byproducts,
      most notably the bisretinoid N-retinylidene-N-retinylethanolamine (A2E). Previous
      studies with human donor eyes have shown a significant mismatch between
      lipofuscin autofluorescence (AF) and A2E distributions. The goal of the current
      project was to examine this relationship in a primate model with a retinal
      anatomy similar to that of humans. Ophthalmologically naive young (<10 years., N
      = 3) and old (>10 years., N = 4) Macaca fascicularis (macaque) eyes, were
      enucleated, dissected to yield RPE/choroid tissue, and flat-mounted on indium-tin
      oxide-coated conductive slides. To compare the spatial distributions of
      lipofuscin and A2E, fluorescence and mass spectrometric imaging were carried out
      sequentially on the same samples. The distribution of lipofuscin fluorescence in
      the primate RPE reflected previously obtained human results, having the highest
      intensities in a perifoveal ring. Contrarily, A2E levels were consistently
      highest in the periphery, confirming a lack of correlation between the
      distributions of lipofuscin and A2E previously described in human donor eyes. We
      conclude that the mismatch between lipofuscin AF and A2E distributions is related
      to anatomical features specific to primates, such as the macula, and that this
      primate model has the potential to fill an important gap in current AMD research.

PMID- 26223374
TI  - Imiquimod and Photodynamic Therapy Are Useful in the Treatment of Porokeratosis
      in Children with Bone Marrow Transplantation.
AB  - Porokeratosis is an uncommon disorder that affects keratinization.
      Immunosuppression may favor the development of porokeratotic lesions. Patients
      who receive allogenic transplants represent a therapeutic challenge to
      dermatologists. We report two cases of porokeratosis in children with bone marrow
      transplant and their excellent response to imiquimod and photodynamic therapy. 

PMID- 26223375
TI  - Refractory acne keloidalis nuchae treated with radiotherapy.
AB  - Acne keloidalis nuchae (AKN) is difficult to treat, and the clinical response is
      usually poor. Few reports have been published about scarring alopecia treated
      with radiotherapy (RT). We report a case of AKN that had been refractory to
      various other treatments but which responded to RT with excellent clinical and
      cosmetic results.

PMID- 26223376
TI  - The investigation of circulating microRNAs associated with lipid metabolism in
      childhood obesity.
AB  - BACKGROUND: Childhood obesity is an increasing health challenge related to
      increased risk of chronic diseases. microRNAs (miRNAs) are noncoding short RNA
      molecules regulating multiple biological processes linked to obesity. OBJECTIVES:
      We aimed at evaluating the association between circulating miRNA levels and lipid
      metabolism in obese and non-obese children and adolescents. METHODS: By
      constituting study group, 45 obese children and adolescents were recruited. To
      perform comparisons with study group, 41 lean controls were matched for age and
      sex. Using real-time quantitative PCR analysis, circulating miRNAs were evaluated
      in both groups. RESULTS: Circulating miR-335 (P < 0.001), miR-143 (P = 0.001) and
      miR-758 (P = 0.006) in obese children were significantly lower than those of
      controls. However, circulating miR-27 (P = 0.032), miR-378 (P < 0.001) and miR
      370 (P = 0.045) in obese children were significantly higher, compared with those
      of controls. In addition, circulating miR-33 in obese children was higher than
      those of controls, but no significant difference was present (P = 0.687).
      CONCLUSION: Our findings showed that a significant association is present between
      circulating miR-370, miR-33, miR-378, miR-27, miR-335, miR-143 and miR-758
      values, and childhood obesity. Low levels of miR-335, miR-143 and miR-758, and
      high levels of miR-27, miR-378, miR-33 and miR-370 may have been responsible for
      elevated triglycerides and low-density lipoprotein (LDL-C) levels, and low level
      of high-density lipoprotein (HDL-C) in obese subjects. Therefore, miRNAs may be a
      good novel biomarker for childhood obesity.

PMID- 26223377
TI  - First report of the invasive mosquito species Aedes koreicus in the Swiss-Italian
      border region.
AB  - BACKGROUND: In 2012 and 2013, an entomological survey of Aedes albopictus, the
      Asian tiger mosquito, was carried out in the border region of southern
      Switzerland and northern Italy, using ovitraps. In July 2013, besides A.
      albopictus already known to the region several unusual eggs were recovered.
      FINDINGS: A total of 548 seemingly different eggs were found within three
      communities: Chiasso (Switzerland), and Como and Brunate (Italy). Proteomic
      diagnostics based on matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-TOF MS) and morphological identification of one reared adult
      revealed the presence of at least 18 A. (Finlaya) koreicus (Edwards, 1917)
      specimens. A. koreicus is a species native to Southeast Asia and is competent to
      transmit Japanese encephalitis and potentially other arboviruses, as well as the
      dog heartworm Dirofilaria immitis. While new to Switzerland, this invasive
      species has previously been reported from Belgium, north-eastern Italy and
      European Russia. CONCLUSIONS: This is the first report of the introduction of
      this exotic mosquito species into Switzerland and Lombardy, Italy, suggesting the
      range of A. koreicus is expanding in Central Europe. As A. koreicus is competent
      to vector pathogens its establishment imposes a risk to public and veterinary
      health. From a technical point of view, the presence of A. koreicus alongside A.
      albopictus requires careful analysis and reliable diagnostics. As a diagnostic
      tool the use of the recently developed MALDI-TOF MS approach has proofed to be a
      very useful approach, particularly since hatching rates of A. koreicus seem to be
      low, making identification by classic morphology difficult, if not impossible.

PMID- 26223378
TI  - Population genetics and evolution of the mangrove rivulus Kryptolebias
      marmoratus, the world's only self-fertilizing hermaphroditic vertebrate.
AB  - The mangrove rivulus, Kryptolebias marmoratus (Rivulidae, Cyprinodontiformes), is
      phylogenetically embedded within a large clade of oviparous (egg laying) and
      otherwise mostly gonochoristic (separate sex) killifish species in the
      circumtropical suborder Aplocheiloidei. It is unique in its reproductive mode: K.
      marmoratus is essentially the world's only vertebrate species known to engage
      routinely in self-fertilization as part of a mixed-mating strategy of selfing
      plus occasional outcrossing with gonochoristic males. This unique form of
      procreation has profound population-genetic and evolutionary-genetic consequences
      that are the subject of this review.

PMID- 26223379
TI  - Progress in the identification of subgroups in ALK-negative anaplastic large-cell
      lymphoma.

PMID- 26223381
TI  - Development and evaluation of anti-malarial bio-conjugates: artesunate-loaded
      nanoerythrosomes.
AB  - Biodegradable cellular carrier has desired properties for achieving effective
      long-term controlled release of drugs having short half life. To reduce the
      undesired effects of drug, advanced drug delivery systems are needed which are
      based on specific cell targeting module. Artesunate (ART) conjugation on
      nanoerythrosomes (NE) can have controlled delivery to avoid drug leakage,
      increase the stability, and reduce cost and toxicities. In this study nanosized
      lipoprotein membrane vesicles bearing ART were prepared by extrusion method.
      Developed ART-NE conjugate formulations were optimized on the basis of vesicle
      morphology, size and size distribution, polydispersity index, integrity of
      membrane, loaded drug concentration, drug leakage, effect of temperature and
      viscosity, syringeability, in vitro release profile and in vivo plasma
      concentration estimation studies. Fourier transform infrared (FTIR) spectroscopy
      reveals that lipid chain order of RBCs are insignificantly affected in moderate
      conditions after ART loading. The formulated ART-NE carrier revealed non
      aggregated, uniformly sized particles with smooth surfaces. The maximum drug
      loading was found to be 25.20 +/- 1.3 MUg/ml. ART-NE formulation was best fit for
      zero order kinetics and was found to be capable of controlled release of drug for
      8 hrs. ART-NE formulation showed good redispersibility with desirable properties
      for parenteral administration. Formulation was stable when subjected to stress by
      centrifugal force of 7500 rpm and could bear turbulence shock of 15 passes from
      hypodermic needle of size 23 gauges. The ART-NE formulation administered
      intravenously showed higher plasma concentration compared to free drug signifying
      not only controlled release but higher rate of in vivo release. The developed
      formulation exhibited zero order release profile as per kinetic study analysis
      suggesting the suitability of carrier for the sustained and targeted delivery of
      ART. The developed ART-NE drug delivery system offers improved pharmacokinetic
      profile with assurance of increased therapeutic efficacy.

PMID- 26223380
TI  - Temporal trends and clonal diversity of penicillin non-susceptible pneumococci
      from meningitis cases from 1996 to 2012, in Salvador, Brazil.
AB  - BACKGROUND: Hospital-based surveillance for pneumococcal meningitis has been
      conducted since January 1996 in the city of Salvador, Brazil. The purpose of this
      study was to describe the temporal evolution of Penicillin Non-Susceptible
      Streptococcus pneumoniae (PNSSP) in regards to serotype distributions and clonal
      diversity recovered from meningitis cases over 17 years. METHODS: Broth
      microdilution was used to identify pneumococcal isolates that were PNSSP (Minimum
      Inhibitory Concentration > 0.12 MUg/ml). The annual incidence rate of meningitis
      cases was calculated. Serotyping was defined using multiplex polymerase chain
      reaction assays and quellung reaction. Genetic diversity of PNSSP isolates was
      assessed using both pulsed-field gel electrophoresis (PFGE) and Multilocus
      Sequence Typing (MLST) analyses. RESULTS: A total of 854 cerebrospinal fluid
      (CSF) culture pneumococcal isolates were tested by broth microdilution method and
      serotyped. A total of 173 (20.3%) were penicillin non-susceptible (PNSSP)
      (Minimum Inhibitory concentration >= 0.12 MUg/ml). The annual incidence of
      meningitis cases declined from 1.65/100,000 population (1996) to 0.2/100,000
      population in 2012 and the rate due to PNSSP declined 82% over the 17-years of
      surveillance. PNSSP isolates were restricted to 13 serotypes, being the most
      common ones serotypes 14 (45.1%; 78/173), 23 F (19.1%; 33/173), 6B (14.4%;
      25/173), 19 F (9.2%; 16/173) and 19A (5.2%; 9/173). Among the PNSSP isolates, 94%
      had serotypes represented in the 10-valent conjugate vaccine (PCV10). The
      predominant serotype 14 clonal groups were identified as PFGE group A/multilocus
      sequence type 66 (ST66) [35.3% (61/173)] and PFGE group GK/ST156 [4.6% (8/173)],
      the latter one associated with high level resistance to penicillin and
      ceftriaxone. CONCLUSIONS: Our results show sustained reductions in pneumococcal
      meningitis cases in the Metropolitan region of Salvador from 1996 to 2012. This
      might reflect a beneficial impact of conjugate vaccines. Continued surveillance
      and further studies need to be conducted to better understanding on PCV10 vaccine
      impact.

PMID- 26223382
TI  - Microneedles for drug and vaccine delivery and patient monitoring.

PMID- 26223383
TI  - The impact of oral contraceptives on cardiometabolic parameters.
AB  - PURPOSE: There is much controversy regarding the use of oral contraceptive pills
      (OCPs) on cardiometabolic parameters, which is why this longitudinal population
      based study was conducted to assess the impact of OCP use and its duration on
      cardiometabolic factors. METHODS: Of 5532 reproductive-aged participants of the
      Tehran lipid and glucose study, 3160 women who met our inclusion criteria were
      subdivided according to the duration of OCPs consumption into four sub-groups:
      (1) Non-users; (2) <11 month users; (3) 12-35 month users, and (4) >=36 month
      users, and their cardiometabolic parameters were compared. RESULTS: No
      statistical significant differences were observed between the cardiometabolic
      parameters of these sub-groups, after further adjustment for confounding factors
      including age, parity, and education, except for mean low-density lipoprotein
      cholesterol which was significantly higher in women who used OCPs for >36 months
      in comparison to non-OCP users. The odds ratio of hypercholesterolemia was
      significantly higher in women who used OCPs for >36 months in comparison to non
      OCP users; being 1.5 times higher than non-users (95 % CI 1.01-2.2). CONCLUSION:
      Results showed that if used for less than 3 years, OCPs have no cardiometabolic
      effects.

PMID- 26223384
TI  - Photobiomodulation and bone healing in diabetic rats: evaluation of bone response
      using a tibial defect experimental model.
AB  - Diabetes mellitus (DM) leads to a delay in bone healing. Thus, some therapeutic
      approaches have been used to accelerate the process of bone repair such as
      photobiomodulation (PBM). Therefore, the present study aimed to evaluate the
      effects of PBM, in different fluences, in bone repair in an experimental model of
      tibial bone defects in diabetic rats. Sixty-four Wistar rats were submitted to a
      surgical procedure to perform bone defect and distributed in four groups:
      diabetic control group (DCG), diabetic laser group 30 J/cm(2) (L30), diabetic
      laser group 60 J/cm(2) (L60), and diabetic laser group 120 J/cm(2) (L120). A 808
      nm Ga-Al-As (DMC Equipment, Sao Carlos, SP, Brazil) laser, 100 mW; 0.028 cm(2);
      3.57 W/cm(2); 30, 60, and 120 J/cm(2); 0.84, 1.68, and 3.36 J; 8, 16, and 33 s
      was used. Animals were euthanized 15 and 30 days after the surgery. Histological,
      morphometric, immunohistochemistry, and biomechanical analyses were performed. In
      the histological and morphometric evaluation, all laser-treated groups showed a
      better histological pattern and a higher amount of newly formed bone compared to
      DCG. An intense RUNX2 immunoexpression was observed in the laser-treated groups,
      15 days after the surgery. Receptor activator of nuclear factor kappa-beta ligand
      (RANK-L) immunohistochemistry analysis showed a significant decrease in the
      immunoreactivity for L30 and L120, 30 days after surgery. There was no
      statistical difference in the biomechanical analysis among the groups. In
      conclusion, PBM, in all fluences used, showed an osteogenic potential in bone
      healing of diabetic rats.

PMID- 26223385
TI  - The cost and intensity of behavioral interventions to promote HIV treatment for
      prevention among HIV-positive men who have sex with men.
AB  - Recently, behavioral prevention interventions for HIV have been criticized as
      being ineffective, costly, or inefficient. In this commentary, using HIV-positive
      men who have sex with men (MSM) as an illustrative high-risk population, we argue
      that the opposite is true-that behavioral interventions for HIV prevention, if
      implemented with the populations who need them, are affordable and critical for
      future prevention efforts. We base this argument on recent evidence showing that
      (1) adherence to antiretroviral treatment (ART) for prevention purposes is
      necessary to suppress HIV replication and reduce transmissibility, (2)
      individuals living with HIV have multiple psychosocial concerns that impact self
      care and moderate the potential effectiveness of health behavior interventions,
      and (3) intensive interventions targeting both concerns together (psychosocial
      and HIV care) can show clinically significant improvement. We follow by comparing
      the cost of these types of interventions to the cost of standard clinical
      treatment for HIV with ART and demonstrate a cost-savings of potential intensive
      behavioral interventions for, in this case, HIV-positive MSM who have
      uncontrolled virus. Keeping this evidence in mind, we conclude that individual
      intervention must remain a mainstay of HIV prevention for certain critical
      populations. 

PMID- 26223386
TI  - Direct Measurement of Macromolecule-Coated Colloid-Mucus Interactions.
AB  - We report measurements of macromolecule-coated colloids interacting with mucus to
      understand colloidal particle diffusion near mucus-coated surfaces. Total
      internal reflection microscopy is used to measure colloids with adsorbed
      poly(ethylene glycol) (PEG), bovine serum albumin (BSA), and polyelectrolyte
      bilayers (PEB) interacting with mucus to obtain kT-scale energy landscapes and
      nanometer-scale diffusivity landscapes. Energy landscapes are quantified as a
      superposition of van der Waals, steric, and tethering potentials, and diffusivity
      landscapes are modeled by considering lubrication in the presence of permeable
      layers. PEG- and BSA-coated colloids have soft repulsion with mucus that could
      enable diffusion of small particles within mucus pores. PEB-coated colloids
      display attractive tethers to mucus that produce irreversible binding. Different
      interaction potentials for each particle coating confirm that the zeta-potential
      is not a successful predictor of particle-mucus interactions and diffusion.
      Diffusivity landscapes show thick mucus layers are permeable to the solvent and
      dominate particle-mucus hydrodynamic interactions relative to the thin,
      impermeable particle coatings. Our results show direct measurements and models to
      understand how particle coating properties (e.g., elasticity, porosity) control
      particle interactions and transport near mucus films to potentially aid the
      design of better particle-based therapeutics and diagnostics. 

PMID- 26223387
TI  - Comparative analysis of essential genes in prokaryotic genomic islands.
AB  - Essential genes are thought to encode proteins that carry out the basic functions
      to sustain a cellular life, and genomic islands (GIs) usually contain clusters of
      horizontally transferred genes. It has been assumed that essential genes are not
      likely to be located in GIs, but systematical analysis of essential genes in GIs
      has not been explored before. Here, we have analyzed the essential genes in 28
      prokaryotes by statistical method and reached a conclusion that essential genes
      in GIs are significantly fewer than those outside GIs. The function of 362
      essential genes found in GIs has been explored further by BLAST against the
      Virulence Factor Database (VFDB) and the phage/prophage sequence database of
      PHAge Search Tool (PHAST). Consequently, 64 and 60 eligible essential genes are
      found to share the sequence similarity with the virulence factors and
      phage/prophages-related genes, respectively. Meanwhile, we find several toxin
      related proteins and repressors encoded by these essential genes in GIs. The
      comparative analysis of essential genes in genomic islands will not only shed new
      light on the development of the prediction algorithm of essential genes, but also
      give a clue to detect the functionality of essential genes in genomic islands. 

PMID- 26223388
TI  - Pancreatectomy with vein reconstruction: technique matters.
AB  - BACKGROUND: A variety of techniques have been described for portal vein (PV)
      and/or superior mesenteric vein (SMV) resection/reconstruction during a
      pancreatectomy. The ideal strategy remains unclear. METHODS: Patients who
      underwent PV/SMV resection/reconstruction during a pancreatectomy from 2005 to
      2014 were identified. Medical records and imaging were retrospectively reviewed
      for operative details and outcomes, with particular emphasis on patency. RESULTS:
      Ninety patients underwent vein resection/reconstruction with one of five
      techniques: (i) longitudinal venorrhaphy (LV, n = 17); (ii) transverse
      venorrhaphy (TV, n = 9); (iii) primary end-to-end (n = 28); (iv) patch venoplasty
      (PV, n = 17); and (v) interposition graft (IG, n = 19). With a median follow-up
      of 316 days, thrombosis was observed in 16/90 (18%). The rate of thrombosis
      varied according to technique. All patients with primary end-to-end or TV
      remained patent. LV, PV and IG were all associated with significant rates of
      thrombosis (P = 0.001 versus no thrombosis). Comparing thrombosed to patent,
      there were no differences with respect to pancreatectomy type, pre-operative
      knowledge of vein involvement and neoadjuvant therapy. Prophylactic aspirin was
      used in 69% of the total cohort (66% of patent, 81% of thrombosed) and showed no
      protective benefit. CONCLUSIONS: Primary end-to-end and TV have superior patency
      than the alternatives after PV/SMV resection and should be the preferred
      techniques for short (<3 cm) reconstructions.

PMID- 26223389
TI  - Ruthenium-Catalyzed O- to S-Alkyl Migration: A Pseudoreversible Barton-McCombie
      Pathway.
AB  - A practical ruthenium-catalyzed O- to S-alkyl migration affords structurally
      diverse thiooxazolidinones in excellent yields. Our studies suggest this
      catalytic transformation proceeds through a pseudoreversible radical pathway
      drawing mechanistic parallels to the classic Barton-McCombie reaction. 

PMID- 26223390
TI  - [Sociedad Chilena de Pediatria. New management, new challenges].

PMID- 26223391
TI  - [Current perspectives on genome-based diagnostic tests in Pediatrics].
AB  - Etiological diagnosis is essential in the clinical management of individual
      patients. Some children with complex medical conditions are subjected to numerous
      testing, known as "diagnostic odyssey", which often gives no conclusive results.
      In recent years, a revolution in genomic medicine is underway with the use of
      technologies that promise to increase the ability to make a diagnosis and reduce
      the time involved. The main advantages and limitations of genomic diagnosis, as
      opposed to usual methodologies are reviewed with an emphasis on Pediatrics. 

PMID- 26223392
TI  - [Nutritional status and socio-epidemiological features of schoolchildren, WHO
      2007].
AB  - INTRODUCTION: Current Chilean childhood obesity fi res are within the highest in
      the world. OBJECTIVE: To describe the nutritional status of Quilpue
      schoolchildren and its relationship with demographic and socioeconomic variables.
      METHODS: The nutritional status (OMS 2007) of 1091 schoolchildren was assessed
      using measurements of height and weight obtained in the "Pilot School Health
      Program" conducted in the schools of the Municipal Corporation of Quilpue, which
      included pupils from kindergarten to 4th grade. The program described above, as
      well as SINAE databases, were used for the Healthcare and School Vulnerability
      Index (SVI) variables, respectively, as well as the the number of hours of
      physical education, type of lunches, and the presence of vendors at school, were
      obtained using a questionnaire in schools. RESULTS: Obesity was observed in 26.3%
      of students, and a further 27.7% were overweight. Obesity was more frequent in
      boys (32.3%) compared to girls (20.1%) (P<.01); in third grade (31.8%) (P=.01);
      if lunches were parental choices (26.7%) (P<.01); and with the presence of school
      vendors (26.3%) (P=.01). No significant differences in socioeconomic status
      regarding BMI were found, but the most vulnerable children (municipal schools,
      high SVI, Fonasa A healthcare) had lower average height and higher rates of
      chronic malnutrition (height <-2 SD). CONCLUSIONS: A high prevalence of obesity
      was found in this study, which highlights the need for monitoring and nutrtional
      intervention strategies at school age (which once finalized, the Healthy Child
      Surveillance does not carry out any more controls), taking into account the most
      vulnerable sectors.

PMID- 26223393
TI  - [Nutritional status in children with intellectual disabilities based on
      anthropometric profile].
AB  - INTRODUCTION: Anthropometric variables such as weight, height and body length in
      children and adolescents with and without intellectual disabilities should be
      studied in connection with nutritional status, physical growth and biological
      maturation. OBJECTIVE: a) to analyze the anthropometric profile based on
      nutritional status, b) to determine the prevalence of overweight and short
      stature c) to propose equations for predicting height from anthropometric
      variables. METHODS: A total of 49 children and adolescents with intellectual
      disabilities, and from a special education school were studied (30 boys and 19
      girls). Weight, height, trunk-cephalic height, forearm and foot length were
      evaluated. The calculation of nutritional status resulted in the establishment of
      nutritional categories: underweight, normal and overweight. RESULTS: The
      anthropometric profile of males varies significantly when classified according to
      nutritional categories (P<.05); however no variations were observed in the girls
      (P>.05). Also, high values of overweight prevalence were observed in both genders
      (43% of boys and 26% of girls). Variables such as age, weight, length of the
      forearm in females, and foot length in males are good predictors of height (R(2)
      = 91-94% males and R(2) = 87% females). CONCLUSIONS: A high percentage of
      overweight cases were observed; therefore, rigorous control and monitoring of
      nutritional status are suggested. The proposed regression equations could be an
      option in schools to easily and simply predict height.

PMID- 26223394
TI  - [Mother-newborn relational risk - Study of prevalence and associated variables].
AB  - INTRODUCTION: Clinical evidence reveals the importance of mother-newborn bonding
      experience for health promoting and maintenance of human life. If the newborn
      lacks care and affection, she/he may develop an attachment disorder. A predictive
      scale regarding the risk of mothernewborn relationships is available, which makes
      possible an early intervention to prevent the development of relational
      disorders. The aim of this study is to apply the Kimelman measurement scale to
      determine the relational risk in mother-newborn pairs, as well as the prevalence
      and the associated biopsychosocial variables. PATIENTS AND METHODS: A cross
      sectional study with a probabilistic sample of 333 mother-infant pairs in
      postpartum maternity at Temuco hospital. The Kimelman mother-newborn attachment
      assessment guide was used. Biopsychosocial variables were obtained from the
      mothers studied. The association of biopsychosocial variables with relational
      risk was analyzed using OR and confidence intervals of 95%. RESULTS: The
      prevalence of high relational risk was 43.8%. The associated biopsychosocial
      variables included, women with no steady partner, single parent, teenage mothers,
      unwanted and unplanned pregnancy. CONCLUSION: Almost half of the mothers were in
      the high risk group. Early identification of relational risk and its related
      variables could help in the intervention in this vulnerable group.

PMID- 26223395
TI  - [Breastfeeding as a protective factor against overweight and obesity among pre
      school children].
AB  - INTRODUCTION: The rates of overweight and obesity among children have
      significantly increased in Chile. OBJECTIVE: To assess the benefits of
      breastfeeding in preventing malnutrition by excessive intake of foods in Chilean
      pre-school children. METHODS: A case-control study was conducted in 2011 on
      pediatric patients treated in a private Chilean healthcare center (San Joaquin
      Medical Center, Catholic University). Gender, age, weight, height, nutritional
      diagnosis, type of feeding during the first 6 months of life, socioeconomic
      status, parental education and obesity, television viewing, and kindergarten
      attendance were analyzed. RESULTS: A total of 209 patients were included in the
      study, 53.1% of whom were male, and 60.3% were predominantly breastfed for the
      first 6 months of life. More than half (51.7%) were eutrophic, 29.7% were
      overweight, and 18.6% obese. The patients were between the ages of 2 and 3 years
      11 months. The crude Odds Ratio of breast-feeding versus formula during the first
      6 months of life in patients with normal weight versus overweight children was
      0.442 (95% CI 0.204-0.961). CONCLUSIONS: It was found that predominantly
      breastfeeding during the first 6 months of life acted as a protective factor
      against malnutrition by excessive intake of foods in Chilean pre-school children
      treated in this private medical center.

PMID- 26223396
TI  - [Dental caries and early childhood development: a pilot study].
AB  - OBJECTIVE: To investigate the association between dental caries and early
      childhood development in 3-year-olds from Talca, Chile. METHOD: A pilot study
      with a convenience sample of 3-year-olds from Talca (n = 39) who attend public
      healthcare centers. Child development was measured by the Psychomotor Development
      Index (PDI), a screening tool used nationally among pre-school children to assess
      language development, fine motor skills and coordination areas. Dental caries
      prevalence was evaluated by decayed, missing, filled teeth (DFMT) and decayed,
      missing, filled tooth surfaces (DFMS) ceo-d and ceo-s indexes. The children were
      divided into two groups according to the PDIscore: those with a score of 40 or
      more were considered developmentally normal (n = 32), and those with a score
      below 40 were considered as having impaired development (n = 7). RESULTS: The
      severity of caries (DMFT) was negatively correlated with PDI (r = -0.82), and
      children with the lowest TEPSI score had the highest DFMT values. The average
      DMFT in children with normal development was 1.31, and 3.57 for those with
      impaired development. CONCLUSION: This pilot study indicates that the severity of
      dental caries is correlated with early childhood development.

PMID- 26223397
TI  - [Low-flow synovial vascular malformation of the knee (hemangiolymphangioma) -
      Case report].
AB  - INTRODUCTION: Low-flow vascular malformation, which usually develops during the
      first stage of infancy, is a rare cause of recurrent effusion of the knee.
      History, laboratory and X-rays are usually non-specific. OBJECTIVE: To describe a
      rare disease in pediatrics, emphasizing the correct classification and suspicion.
      CASE REPORT: A case is presented of a two-year-old patient with a history of
      effusion of the right knee who required multiple hospitalizations and antibiotic
      treatments. Laboratory work-up was normal. Plain X-rays of the knee revealed no
      bone changes. MR imaging reported low-flow vascular malformation. Surgical
      resection was performed, evidencing vascular lesion among the muscle fibers of
      the vastus lateralis of quadriceps until the capsule of the knee, as well as
      dissection of the fibers until the vastus lateralis of the right leg. Histology
      was consistent with low-flow vascular malformation. Due to the benign outcome and
      favorable evolution, an outpatient management was possible. CONCLUSIONS: Although
      low-flow synovial vascular malformation is a rare disease among the pediatric
      population, it should be considered in the differential diagnosis of patients
      with repeated hemarthrosis and no history of either coagulopathy or hemophilia.

PMID- 26223398
TI  - [Sjogren's syndrome - case report].
AB  - INTRODUCTION: Sjogren's syndrome (SS) is a chronic autoimmune disease that
      primarily affects the lacrimal and salivary exocrine glands. In children, it is a
      rare condition. OBJECTIVE: To present the case of an adolescent with non-specific
      symptoms, but with a clinical suspicion of SS. CASE REPORT: A male 12-year old
      patient, with history of arthralgias for 3 years and suspicion of xerophthalmia.
      Physical examination showed mild conjunctival congestion, dry mouth and
      hypermobility of the knees. Laboratory work: blood count and ESR were normal,
      antinuclear antibodies (+) > 60, Ro (+) > 60 U, and rheumatoid factor
      concentration (+) 160 IU / ml. SS was suspected, and a study was carried out:
      Schirmer test determined mild dry eye, salivary gland scintigraphy showed parotid
      and submandibular gland dysfunction, and salivary gland biopsy reported focal
      lymphocytic acinar and periductal infiltration. SS was confirmed and treated with
      prednisone 7.5mg/day and hydroxychloroquine 200mg/day, and local treatment, with
      good response. CONCLUSIONS: The diagnostic criteria for SS in adults identified
      only 39% of pediatric patients, due to the low frequency of sicca symptoms. Still
      there are no validated diagnostic criteria for children. A good diagnosis will
      alleviate symptoms, prevent complications and detect associated diseases.

PMID- 26223399
TI  - [Cutaneous manifestations of cystic fibrosis in an infant: acrodermatitis
      enteropathica and gray hair].
AB  - INTRODUCTION: Cutaneous manifestations at the time of CF diagnosis are rare.
      OBJECTIVE: To describe the case of an infant with an unusual cutaneous
      presentation of cystic fibrosis. CASE REPORT: The case is presented of an infant
      with delayed physical growth at two months, and at the age of four months,
      presented with a skin rash and gray hair. Tests revealed the presence of
      hypoproteinemia and anemia, with the diagnosis of Cystic Fibrosis being confirmed
      by genetic testing. The rash was completely resolved after pancreatic enzyme
      replacement therapy. This is the second gray hair case reported in children with
      this disease. CONCLUSION: Metabolic diseases such as cystic fibrosis should be
      suspected in malnourished children who develop skin disorders.

PMID- 26223400
TI  - [Limitation of the therapeutic effort in pediatric intensive care].
AB  - Pediatric intensive care is a relatively new medical specialty, which has
      experienced significant technological advances in recent years. These
      developments have led to a prolongation of the dying process, with additional
      suffering for patients and their families, creating complex situations, and often
      causing a painful life extension. The term, limitation of the therapeutic effort
      refers to the adequacy and/or proportionality of the treatment, trying to avoid
      obstinacy and futility. The English literature does not talk about limitation of
      treatments, but instead the terms, withholding or withdrawal of life-sustaining
      treatment, are used. The removal or the non-installation of certain life support
      measures and the absence of CPR are the types of limitation most used. Also,
      there is evidence of insufficient medical training in bioethics, which is
      essential, as most doctors in the PICU discuss and make decisions regarding the
      end of life without the opinion of bioethicists. This article attempts to review
      the current status of knowledge concerning the limitation of therapeutic efforts
      to support pediatric clinical work. 

PMID- 26223401
TI  - [Twenty observations on spinal poliomyelitis. Revista Chilena de Pediatria 1938].

PMID- 26223402
TI  - [Viewing competition reality shows and risk of eating disorders in adolescent
      schoolchildren].

PMID- 26223403
TI  - Life span variation in 13 Drosophila species: a comparative study on life span,
      environmental variables and stress resistance.
AB  - Recently, heterogeneity of the environment has been suggested as an important
      player in the evolution of life span variation. Established ageing theories
      propose that life span variation is the result of coevolution with other traits,
      such as stress resistance. This study aimed to compare these alternative
      hypotheses by examining the relationship between four environmental variables and
      different types of stress resistance traits with life span in 13 Drosophila
      species originating from tropical, subtropical and temperate environments
      (ecotypes). Average life span was found to differ significantly both between
      species and sexes, but only male life span correlated with the environment and
      cold resistance. While controlling for phylogeny, the environmental variable
      precipitation seasonality and resistance against cold-induced stress explained
      most variation in male life span. Furthermore, male life span varied between
      species in a manner represented by environmental variables linked to the
      different ecotypes, such that tropical species lived longer and were less cold
      resistant. The current results suggest that general mechanisms underlying stress
      resistance and life span are unlikely. In addition, our results point to the
      environment independently shaping variation in life span and cold resistance
      rather than genetic interactions. 

PMID- 26223404
TI  - Activation of Carbon Dioxide by Silyl Triflate-Based Frustrated Lewis Pairs.
AB  - Silyl triflates of the form R4-n Si(OTf)n (n=1, 2; OTf=OSO3 CF3 ) are shown to
      activate carbon dioxide when paired with bulky alkyl-substituted Group 15 bases.
      Combinations of silyl triflates and 2,2,6,6-tetramethylpiperidine react with CO2
      to afford silyl carbamates via a frustrated Lewis pair-type mechanism. With
      trialkylphosphines, the silyl triflates R3 Si(OTf) reversibly bind CO2 affording
      [R'3 P(CO2 )SiR3 ][OTf] whereas when Ph2 Si(OTf)2 is used one or two molecules of
      CO2 can be sequestered. The latter bis-CO2 product is favoured at low
      temperatures and by excess phosphine.

PMID- 26223405
TI  - Improving performance amongst nursing students through the discovery of
      discrepancies during simulation.
AB  - Discrepancy creation is a form of self-regulated learning which can be used to
      improve individual performance. Discrepancy can be created as a result of
      comparison against an occupational standard or when an individual strives to
      achieve higher personal goals. This study explores the process of discrepancy
      discovery and reduction following simulation sessions. Second year under-graduate
      nursing students undertook three simulation sessions over a one year period.
      After each session the participants completed a series of visual analogue scales
      to rate their own performance and the perceived performance of peers, final year
      student and a newly registered nurse. Once discrepancy had been identified,
      participants were asked to produce a short written action plan on how the
      discrepancy could be addressed and to work on this action plan between sessions.
      A total of 70 students completed discrepancy scores for all three scenarios. The
      most common areas of discrepancy were understanding physiology, understanding
      medicines and pharmacology, patient assessment and handover (hand off). Wilcoxon
      Signed Ranks suggested a statistically significant difference between student
      scores in all areas with the exception of team-work. All of the participants used
      peers as their comparator when identifying discrepancy. There was also a
      statistically significant difference in the scores following each simulation
      session suggesting improved performance. 

PMID- 26223406
TI  - Erratum to: P2 receptors in atherosclerosis and postangioplasty restenosis.

PMID- 26223407
TI  - The social gradient in preventive healthcare use: what can we learn from socially
      mobile individuals?
AB  - Little is known about the origins of the stratified nature of preventive health
      behaviour. In this paper, we introduce theory and methodology from the field of
      social mobility research. Intergenerational socially mobile individuals can
      provide insights into the central discussion about how health lifestyles or
      cultural health capital develop over the life course, as they have encountered
      different contexts of socialisation, each with its own characteristic health
      related practices. We study the use of regular mammography screening by Belgian
      women using data from the Survey of Health, Aging and Retirement and we
      operationalise social mobility as occupational mobility using the International
      Standard Classification of Occupations (ISCO-88). By means of diagonal reference
      models, we are able to discern the effects of the social position of origin, the
      social position of destination and social mobility itself, contrary to the less
      rigorous linear regression approach that prevails in health behaviour research.
      As expected, the take up of mammography screening is strongly influenced by
      social position. It seems that both upwardly and downwardly mobile women adapt to
      the mammography screening practices in their position of destination. This study
      shows the potential for social mobility research to enrich the debate on health
      lifestyles. 

PMID- 26223408
TI  - Epidemiology of painful procedures performed in neonates: A systematic review of
      observational studies.
AB  - BACKGROUND AND OBJECTIVE: Procedural pain in neonates has been a concern in the
      last two decades. The purpose of this review was to provide a critical appraisal
      and a synthesis of the published epidemiological studies about procedural pain in
      neonates admitted to intensive care units. The aims were to determine the
      frequency of painful procedures and pain management interventions as well as to
      identify their predictors. DATABASES AND DATA TREATMENT: Academic Search, CINAHL,
      LILACS, Medic Latina, MEDLINE and SciELO databases were searched for
      observational studies on procedural pain in neonates admitted to intensive care
      units. Studies in which neonatal data could not be extracted from the paediatric
      population were excluded. RESULTS: Eighteen studies were included in the review.
      Six studies with the same study duration, the first 14 days of the neonate life
      or admission in the unit of care, identified 6832 to 42,413 invasive procedures,
      with an average of 7.5-17.3 per neonate per day. The most frequent procedures
      were heel lance, suctioning, venepuncture and insertion of peripheral venous
      catheter. Pharmacological and nonpharmacological approaches were inconsistently
      applied. Predictors of the frequency of procedures and analgesic use included the
      neonate's clinical condition, day of unit stay, type of procedure, parental
      presence and pain assessment. The existence of pain protocols was not a predictor
      of analgesia. CONCLUSIONS: Painful procedures were performed frequently and often
      with inadequate pain management. Unlike neonate clinical factors, organizational
      factors may be modified to promote a context of care more favourable to pain
      management.

PMID- 26223409
TI  - Healthcare waste management practice in the West Black Sea Region, Turkey: A
      comparative analysis with the developed and developing countries.
AB  - The need for proper healthcare waste management has been a crucial issue in many
      developing countries as it is in Turkey. The regulation regarding healthcare
      wastes in Turkey was updated in 2005 in accordance with the European Union (EU)
      waste directives, but it still falls behind meeting the requirements of current
      waste treatment technologies. Therefore, this study aims to reveal deficiencies,
      inconsistencies, and improper applications of healthcare waste management in the
      western part of the Turkish Black Sea Region. In this study, it was revealed that
      nearly 1 million people live in the region, resulting in 5 million hospital
      admissions annually. All the healthcare waste produced (1000 tons yr(-1)) is
      treated in an autoclave plant. However, treating some categories of healthcare
      wastes in autoclave units mismatches with the EU waste regulations, as
      alternative treatment technologies are not technically able to treat all types of
      healthcare wastes. A proper waste management system, therefore, requires an
      internal segregation scheme to divert these wastes from the main healthcare waste
      stream. The existing malpractice in the region could cause serious health
      problems if no measure is taken urgently. It is expected that healthcare waste
      management in the region and then all across Turkey will be improved with the
      significant deficiencies and inconsistencies pointed out in this research.
      IMPLICATIONS: In developed countries, specific rules and regulations have already
      been implemented along with the recommendations for handling of healthcare waste.
      However, in Turkey, these wastes are treated in autoclave units, which mismatches
      with the European Union waste regulations, as alternative treatment technologies
      are not technically capable to treat all types of healthcare wastes. The existing
      malpractice could cause serious health problems if no measure is taken urgently.
      The authors demonstrated the existing status of Turkish waste management and
      revealed deficiencies, inconsistencies, and improper applications in comparison
      with developed and developing nations to align Turkish practice to European Union
      requirements.

PMID- 26223410
TI  - Diabetes News.

PMID- 26223411
TI  - Temporal processing in the auditory brainstem response by full-term 6-week- and 9
      month-old infants.
AB  - Early auditory temporal processing abilities are important for language
      acquisition and for later reading abilities. In the present study, auditory
      brainstem responses (ABRs) were recorded in a forward-masking paradigm in
      healthy, full-term infants aged 6 weeks (n = 111) and 9 months (n = 62). Our
      purpose was to establish normative values of forward-masking ABRs and investigate
      the development of auditory temporal processing in infants at these ages. Infants
      were presented with pairs of stimuli (an initial "masker" followed by a "probe")
      separated by different time intervals (8, 16, and 64 ms). Results showed that as
      masker-probe intervals became longer and as infants got older, Wave V latency to
      the probe shortened. The greatest improvements in Wave V latencies from 6 weeks
      to 9 months of age were observed in the 64-ms masker-probe interval, suggesting
      that central auditory nervous system related to the temporal processing at this
      interval might undergo rapid development during the first year of life.

PMID- 26223413
TI  - Philosophy and mathematics.

PMID- 26223414
TI  - [Bachelard and the mathematical pulsation].
AB  - The working mathematician knows a specific gesture named " mathematical pulsation
      ", a necessary creative moving in diagrams of thoughts and interpretations of
      mathematical writings. In this perspective the fact of being an object is
      definitely undecided, and related to the game of relations. The purpose of this
      paper today is to construct this pulsation, starting from the epistemology of
      Bachelard, concerning mathematics as well as mathematical physics. On the way, we
      recover links between ideas of Bachelard and more recent specific propositions by
      Gilles Ch-let, Charles Alunni, or Rene Guitart. Also are used authors like
      Jacques Lacan, Arthur Koestler, Alfred N. Whitehead, Charles S. Peirce. We
      conclude that the mathematical work consists with pulsative moving in the space
      of diagrams; we claim that this view is well compatible with the Bachelard's
      analysis of scientific knowledge: the intellectual or formal mathematical data
      preceeds the empirical objects, and in some sense these objects result from the
      pulsative gestures of the thinkers. So we finish with a categorical scheme of the
      pulsation. 

PMID- 26223415
TI  - [Gaston Bachelard anagogical reverie and surrational at stake].
AB  - The latest studies on epistemological thought of Gaston Bachelard, especially in
      France and Italy, they are highlighting some fundamental issues, such as creative
      and propulsive assigned to mathematics in the construction of physical reality.
      The studies of Bachelard on the quantum mechanics of the '30s, and especially on
      the theoretical physics of Paul Dirac, introduced a particular concept of
      "anagogical reverie" precisely in order to understand the increasingly abstract
      and creative thinking of mathematics in the various levels of physical reality.
      In the wake of what Federigo Enriques called "mathematical poetry", Bachelard
      comes to propose a real "noumenologie mathematique" which characterizes the
      contemporary scientific thought and which provides the basis epistemic
      appropriate to understand the 'rational effectiveness' of mathematics and the
      real meaning of their application to the real. For these reasons, Bachelard in
      the '30s used a new term to describe his rationalist engagement, the
      "surrationalisme", just to understand in depth what Enriques called the "implicit
      philosophy" in sciences, the "pensee des sciences", where mathematics, thanks to
      the "anagogical reverie", put in place continue "enjeux" of the rational. 

PMID- 26223412
TI  - Bioactive nanoparticles improve calcium handling in failing cardiac myocytes.
AB  - AIMS: To evaluate the ability of N-acetylglucosamine (GlcNAc) decorated
      nanoparticles and their cargo to modulate calcium handling in failing cardiac
      myocytes (CMs). MATERIALS & METHODS: Primary CMs isolated from normal and failing
      hearts were treated with GlcNAc nanoparticles in order to assess the ability of
      the nanoparticles and their cargo to correct dysfunctional calcium handling in
      failing myocytes. RESULTS & CONCLUSION: GlcNAc particles reduced aberrant calcium
      release in failing CMs and restored sarcomere function. Additionally,
      encapsulation of a small calcium-modulating protein, S100A1, in GlcNAc
      nanoparticles also showed improved calcium regulation. Thus, the development of
      our bioactive nanoparticle allows for a 'two-hit' treatment, by which the cargo
      and also the nanoparticle itself can modulate intracellular protein activity.

PMID- 26223416
TI  - [Althusser/Bachelard: An epistemological break at stake].
AB  - Louis Althusser claimed that Bachelard and french historical epistemology were an
      influence on his own attempt to reconstruct Marxism. Yet, both the nature and the
      working of this influence are far from obvious. The links between Bachelard and
      Althusser have often been reduce to a serie of formulas that endeed up
      concealing, rather than revealing, the way Althusser used epistemology and
      philosophy of science. 

PMID- 26223417
TI  - Law and rule in the Essay towards solving a problem in the doctrine of chances.
AB  - In his famous Essay towards solving a problem in the doctrine of chances, Bayes
      calculates probabilities as chances to be in the right in one's guess or as
      fractions of certainty. He was led to use two schemas. The first one is a
      monetary schema. But he forwarded a second schema of a square table on which a
      ball is thrown and the points where it rests are located and recorded. This
      schema was to him the best possible one to give shape to the problem of
      ascertaining the degree of trust to be given to a guess when, having at one's
      disposal only a small number of data about the conjunction of subsequent events,
      one extrapolates from this small number to a greater number. The purpose of my
      paper is to examine the nature of the "I" of the "I guess", which must be
      understood in a transcendental or intersubjective way rather than in a private or
      individual sense. But then, the right interpretation of the Bayesian "I guess"
      might well be found in terms of the theory of games, as convincingly expounded by
      J. C. Harsanyi. 

PMID- 26223418
TI  - Econometricians, your probabilities are close to their end. Economists, now look
      for a new world!
AB  - The article examines several stochastic layers of epistemic reasoning at work in
      econometrics and in the current economic methods: (1) the argumentative level;
      (2) the reasoning based on the analogy with gambling; (3) the models based on
      analytical calculation of probabilities, where the phenomenon is held centered,
      its uncertainty being controlled by white noise as to its fluctuation; (4) the
      axiomatic calculus. Entanglement of these strata is observed. The article calls
      for reflexion on the topic. Doing so, it introduces the concept of stochastic
      cognitive artifacts. 

PMID- 26223419
TI  - [Two problems regarding transitive epistemological mathematics].

PMID- 26223421
TI  - Ultrathin descemet stripping automated endothelial keratoplasty using a
      femtosecond laser to cut grafts from the endothelial side.

PMID- 26223420
TI  - Gastroprotective bio-guiding study of fruits from Mimusops balata.
AB  - Mimusops spp. is used as plant-based antiulcer drugs in Indian traditional
      medicine. In this study, a bio-guiding study of methanolic extracts of Mimusops
      balata edible fruits was performed to identify an antiulcer gastric compound. The
      gastric lesions induced by HCl/ethanol in mice were significantly improved by
      methanolic extract from seed (MESe, 300 mg/kg), but not by methanolic extract
      from peel (MEPe, 300 mg/kg) or pulp (MEPu, 300 mg/kg), when compared to the
      vehicle group. Treatment with MESe also decreased gastric ulceration induced by
      indomethacin. The antiulcerogenic activity of MESe appears to involve the
      maintainance of GSH levels, reduction of LPO content, inhibition of neutrophil
      migration (as evidenced by a decrease in the MPO activity) and a potent free
      radical scavenger activity (IC50 = 3.4 MUg/ml). Moreover, MESe decrease the
      gastric volume, pH, total acidity, and pepsin activity in the gastric juice.
      Exceptionally, MESe showed a high content of phenolic compound, identified by
      layer chromatography and Folin-Ciocalteu reagent. Considering the better
      pharmacological and phytochemical profile, MESe was successively partitioned and
      resulted in isolation and identification of a constituent, the flavonoid
      taxifolin, identified by spectroscopic methods ((1)H, (13)C NMR, and HPLC).
      Taxifolin also inhibited the ulcerogenic effect of HCl/ethanol at a low dose of
      1.14 mg/kg and inhibited in vitro H+/K(+)-ATPase activity by 41% at a
      concentration of 100 MUg/ml. Taken together, these results evidenced the
      gastroprotective potential of fruits from M. balata and showed that this effect
      is exclusive to the seeds.

PMID- 26223422
TI  - Detection of rotavirus species A, B and C in domestic mammalian animals with
      diarrhoea and genotyping of bovine species A rotavirus strains.
AB  - Rotaviruses (RVs) are a major cause of neonatal diarrhoea in humans and animals
      worldwide. In this study, 425 faecal samples were collected between 1999 and 2013
      from diarrhoeic livestock and companion animals at different locations in Germany
      and tested for RVs. A previously published real-time RT-PCR assay was optimized
      for detection of a larger variety of RV species A (RVA) strains, and real-time RT
      PCR assays for detection of RV species B (RVB) and C (RVC) were newly developed.
      The detection limits of the assays were 1.54*10(2), 3.95*10(2) and 3.60*10(3)
      genome copies for RVA, RVB and RVC, respectively. RVA was identified in 85.2% of
      bovine samples, 51.2% of porcine samples, 50.0% of feline samples, 43.2% of
      equine samples and 39.7% of canine samples. RVB was found in 3.0% of bovine
      samples, 2.7% of equine samples and 1.6% of porcine samples. RVC was detected in
      31.0% of porcine samples, 21.7% of feline samples, 9.0% of canine samples and
      6.0% of bovine samples. For genotyping, 101 RVA-positive bovine samples were
      further analysed by semi-nested RT-PCR. Genotype combination G6P[5] was most
      frequently detected (67.3% of samples), followed by G6P[11] (13.9%), G10P[5]
      (4.0%), G8P[11] (3.0%), G6P[1] (1.0%), and G10P[11] (1.0%). Mixed RVA infections
      were detected in 5.9% of samples; no or incomplete typing was possible in 4.0% of
      the samples. This first overview on RV species and RVA genotypes in diarrhoeic
      livestock and companion animals from Germany indicates a broad circulation of a
      large variety of RVs. 

PMID- 26223423
TI  - Early loading of splinted implants supporting a two-unit fixed partial denture in
      the posterior maxilla: 13-month results from a randomized controlled clinical
      trial of two different implant systems.
AB  - OBJECTIVES: The aim of this study was to evaluate early-loaded implants
      supporting a two-unit fixed dental prosthesis in the posterior maxilla and to
      compare the clinical and radiological outcomes of two different implant systems
      in terms of success rates, implant stability quotient (ISQ) values, and peri
      implant parameters. MATERIALS AND METHODS: Thirty patients with the unilateral
      loss of two consecutive maxillary posterior teeth were randomly assigned to two
      different implant systems: SLActive Bone level implant (Institut Straumann AG,
      Basel, Switzerland) in the control group and CMI IS-II active implant (Neobiotech
      Co., Seoul, Korea) in the experimental group. The patients received provisional
      and definitive two-unit fixed prostheses at 4 weeks and 6 months after implant
      surgery, respectively. The peak insertion torque was recorded at surgery. The
      stability of each implant was evaluated during surgery and at 2, 3, and 4 weeks
      and 6 and 13 months after implant placement by means of ISQ values. In addition,
      periapical radiographs and peri-implant parameters were taken throughout the
      trial. RESULTS: Overall, comparable results were obtained between the control and
      experimental groups in terms of insertion torque, ISQ values, marginal bone loss,
      and peri-implant soft tissue parameters. All 60 implants had 100% of success
      rate. The average insertion torque was 36.83 +/- 6.09 (control) and 35.33 +/-
      3.20 (test) Ncm. The ISQ values remained steady until 4 weeks and then increased
      with statistical significance during 4 weeks to 13 months after surgery. Both
      groups exhibited no stability dip during the early phase of healing. The average
      marginal bone loss from the baseline of implant placement for the control and
      experimental groups was 0.38 and 0.45 mm after 4 weeks and 0.98 and 0.61 mm after
      13 months. All of the soft tissue parameters were within normal limits.
      CONCLUSIONS: The results of this study indicate that the concept of early loading
      at 4 weeks after placement in the posterior maxilla can be an effective treatment
      option, even in the areas of low bone density, when implants satisfy the
      inclusion criteria of minimum insertion torque and ISQ of 30 Ncm and 65,
      respectively.

PMID- 26223424
TI  - Continuous and long-term treatment is more important than dosage for the
      protective effect of thiazide use on bone metabolism and fracture risk.
AB  - BACKGROUND: Data from observational studies have suggested that thiazide
      diuretics protect against fractures. Few studies have investigated time frames
      from initiation of treatment to fracture occurrence. OBJECTIVE: To evaluate the
      time to spinal, hip, femur, wrist and upper extremity fracture occurrence before
      and after thiazide exposure. METHODS: A matched retrospective cohort study of
      patient information from national Danish patient databases was conducted.
      Patients with reimbursed prescriptions for noncompounded thiazide diuretics with
      potassium supplementation (Anatomical Therapeutic Chemical classification system
      code C03AB) between 1996 and 2011 were matched with nonexposed control subjects
      by date of birth and gender. Weekly odds ratios (ORs) of fracture occurrence and
      total incidence rates (IRs) and incidence rate ratios (IRRs) of fracture risk
      were calculated for the periods before treatment initiation, weeks 1-42 and weeks
      43-780. RESULTS: A total of 1,602,141 'thiazide exposure periods' (46,8271
      individuals) and 1,530,233 'nonexposure periods' (655,399 individuals) were
      included in the analysis. Thiazide use was associated with factors of increased
      de novo fracture risk. Weekly adjusted fracture risk between exposure and
      nonexposure was increased prior to commencing thiazide therapy, further
      increasing from weeks 1-42 weeks and then decreasing gradually from weeks 43-780.
      There was a decreasing trend in total age-adjusted risk during these periods: IRR
      [95% confidence interval 1.44 [1.42; 1.47], 1.27 [1.24; 1.29] and 1.14 [1.11;
      1.18], respectively. Prescription patterns showed several treatment breaks
      amongst thiazide users. CONCLUSIONS: It appears that thiazides reduce the
      background risk of fracture that is increased prior to commencing therapy. Long
      duration and continuity of thiazide exposure seems to be important to obtain this
      protective effect on fracture risk, but we have found in this study that this
      approach is not always used in clinical practice.

PMID- 26223425
TI  - Assessing adherence to guidelines with administrative data in psychiatric
      outpatients.
AB  - RATIONALE, AIMS AND OBJECTIVES: To assess (feasibility) of adherence to treatment
      guidelines among outpatients with common mental disorders in a routine Dutch
      clinical outpatient setting for common mental disorders using administrative
      data. METHODS: In a retrospective cohort study, we analysed routinely collected
      administrative data of 5346 patients, treated for mood, anxiety or somatoform
      disorders with pharmacotherapy, psychotherapy or a combination of both. Available
      administrative data allowed assessment of guideline adherence with a disorder
      independent set of five quality indicators, assessing psychotherapy,
      pharmacotherapy, a combination of both and routine outcome measurements (ROM)
      during diagnostic and therapeutic phases. Associations between the socio
      demographic variables age, gender, clinical diagnosis and treatment type on the
      one hand and non-adherence to guidelines were tested using logistic regression
      analysis. RESULTS: Patients were aged 39.5 years (SD 13.0) on average. The
      majority of patients were treated with a combination of pharmacotherapy and
      psychotherapy (50.1%), followed by psychotherapy (44.2%) and pharmacotherapy
      (5.6%). The majority of patients were suffering from a mood disorder (50.0%),
      followed by anxiety (43.9%) and somatoform disorders (6.1%). A diagnosis of
      anxiety or somatoform disorder was associated with higher odds of suboptimal
      duration [odds ratio (OR): 1.55 and 1.82[ and suboptimal frequency of
      psychotherapeutic treatment (OR of 0.89 and 0.63), and absence of ROM in the
      diagnostic phase (ORs 1.31 and 1.36, respectively) compared with depressive
      disorders. No ROM in the diagnostic phase was also predicted for by increasing
      age (ORs for the age categories of 56 and older of 1.48). CONCLUSIONS: In this
      proof of principal study, we were able to assess some key indicators assessing
      adherence to clinical guidelines by using administrative data. Also, we could
      identify predictors of adherence with simple parameters available in every
      administrative data. Administrative data could help to monitor and aid guideline
      adherence in routine care, although quality may vary between settings.

PMID- 26223427
TI  - Aspartate aminotransferase to platelet ratio and fibrosis-4 as biomarkers in
      biopsy-validated pediatric cystic fibrosis liver disease.
AB  - Up to 10% of cystic fibrosis (CF) children develop cirrhosis by the first decade.
      We evaluated the utility of two simple biomarkers, aspartate aminotransferase to
      platelet ratio index (APRI) and FIB-4, in predicting degree of fibrosis in
      pediatric CF liver disease (CFLD) validated by liver biopsy. In this
      retrospective, cross-sectional study, 67 children with CFLD had dual-pass liver
      biopsies and 104 age- and sex-matched CF children without liver disease (CFnoLD)
      had serum to calculate APRI and FIB-4 collected at enrollment. CFLD was defined
      as having two of the following: (1) hepatomegaly+/-splenomegaly; (2)>6 months
      elevation of ALT (>1.5* upper limit of normal ULN); or (3) abnormal liver
      ultrasound findings. Biopsies were staged according to Metavir classification by
      two blinded pathologists. Receiver operating characteristic (ROC) analysis and
      continuation ratio logistic regression were performed to assess the
      predictability of these biomarkers to distinguish CFLD from CFnoLD and determine
      fibrosis stage-specific cut-off values. The AUC for APRI was better than FIB-4
      (0.75 vs. 0.60; P=0.005) for predicting CFLD and severe CFLD (F3-F4) (0.81). An
      APRI score>0.264 demonstrated a sensitivity (95% confidence interval [CI]) of
      73.1% (60.9, 83.2) and specificity of 70.2% (60.4, 78.8) in predicting CFLD. A
      50% increase in APRI was associated with a 2.4-fold (95% CI: 1.7, 3.3) increased
      odds of having CFLD. APRI demonstrated full agreement with histology staging 37%
      of the time, but was within one stage 73% of the time. Only FIB-4 predicted
      portal hypertension at diagnosis (area under the receiver operator characteristic
      curve [AUC 0.91; P<0.001). CONCLUSION: This is the first liver biopsy-validated
      study of APRI and FIB-4 in pediatric CFLD. APRI appears superior to FIB-4 in
      differentiating CFLD versus CFnoLD. APRI also exhibited a high AUC in predicting
      severe liver fibrosis with specific cutoffs for lower stages.

PMID- 26223428
TI  - The role of Pannexin gene variants in schizophrenia: systematic analysis of
      phenotypes.
AB  - Pannexins are a group of brain-expressed channel proteins thought to be
      regulators of schizophrenia-linked pathways including glutamate release, synaptic
      plasticity and neural stem proliferation. We got evidence for linkage of a
      catatonic phenotype to the PANX2 locus in a family study. Aim of our study was to
      evaluate the role of Pannexins in schizophrenia and clinical phenotypes,
      particularly with regard to periodic catatonia. We genotyped six single
      nucleotide polymorphisms at PANX1, five at PANX2 and three at PANX3 in 1173
      German cases with schizophrenia according to DSM-5 and 480 controls. Our sample
      included 338 cases with periodic catatonia corresponding to Leonhard's
      classification. Association with schizophrenia according to DSM-5 was limited to
      genotype rs4838858-TT [p = 0.02, odds ratio (OR) 3.1] and haplotype rs4838858T
      rs5771206G (p = 0.02, OR 2.7) at PANX2. We found no significant association with
      clinical phenotypes. Our limited findings do not support a major contribution of
      PANX1-3 to disease risk of schizophrenia according to DSM-5. We cannot confirm an
      association of the PANX2 loci at chromosome 22q13 with periodic catatonia. 

PMID- 26223426
TI  - Genes associated with Parkinson's disease: regulation of autophagy and beyond.
AB  - Substantial progress has been made in the genetic basis of Parkinson's disease
      (PD). In particular, by identifying genes that segregate with inherited PD or
      show robust association with sporadic disease, and by showing the same genes are
      found on both lists, we have generated an outline of the cause of this condition.
      Here, we will discuss what those genes tell us about the underlying biology of
      PD. We specifically discuss the relationships between protein products of PD
      genes and show that common links include regulation of the autophagy-lysosome
      system, an important way by which cells recycle proteins and organelles. We also
      discuss whether all PD genes should be considered to be in the same pathway and
      propose that in some cases the relationships are closer, whereas in other cases
      the interactions are more distant and might be considered separate. Beilina and
      Cookson review the links between genes for Parkinson's disease (red) and the
      autophagy-lysosomal system. They propose the hypothesis that many of the known PD
      genes can be assigned to pathways that affect (I) turnover of mitochondria via
      mitophagy (II) turnover of several vesicular structures via macroautophagy or
      chaperone-mediated autophagy or (III) general lysosome function. This article is
      part of a special issue on Parkinson disease.

PMID- 26223429
TI  - Trichoscopic changes in hair during treatment of hirsutism with 1064-nm
      neodymium:yttrium-aluminum-garnet laser.
AB  - BACKGROUND: Laser hair removal has become an accepted form of long-term hair
      reduction and is now one of the most common dermatologic procedures. Trichoscan
      is a validated method of assessing hair length, thickness, and density and growth
      rate using dermoscopy. OBJECTIVE: The study aimed to evaluate the trichoscopic
      changes during treatment of hirsutism with 1064-nm neodymium:yttrium-aluminum
      garnet laser. METHODS: Seventy patients with idiopathic facial hirsutism
      referring to the laser centers of Al-Azhar University hospital (Asyut and Cairo)
      between December 2012 and October 2014 were enrolled in this open-label,
      multicentric study. All participants received six sessions of 1064-nm Nd:YAG
      laser at 4-week intervals. Mean hair density/cm(2) , percentage of
      terminal/vellus hair ratio, and hair thickness (mm) were assessed at baseline and
      1 month after each session for six sessions using trichoscan. RESULTS: Seventy
      female patients completed the study protocol. At the final visit, mean hair
      density, terminal/vellus hair ratio, and hair thickness were significantly
      decreased from baseline (73.7 + 20.6, 72.5 + 14.7, 0.095 + 0.02, respectively) to
      (19.4 + 5.6, 21.3 + 5.2, 0.02 +/- 0.007, respectively) (P < 0.05 for each).
      CONCLUSION: One thousand and sixty-four-nm Nd:YAG laser is an effective and safe
      method in the reduction of unwanted facial hair. Trichoscan is an easy and more
      accurate method in monitoring the treatment of hair disorders.

PMID- 26223430
TI  - Zonal differences in meniscus MR relaxation times in response to in vivo static
      loading in knee osteoarthritis.
AB  - This study assessed the effects of static loading on MRI relaxation times of
      menisci in individuals with and without radiographic knee OA. High-resolution
      fast spin-echo (FSE) and T(1rho)/T(2) relaxation time MR sequences were obtained
      with and without loading at 50% body weight in 124 subjects. T(1rho)/T(2)
      relaxation times were calculated in menisci, and meniscus lesions were assessed
      through clinical grading. Student's t-test compared OA and control unloaded
      relaxation times as well as within-group changes with loading, Generalized Linear
      Models evaluated zonal variation, and ANCOVA compared loading response between
      groups. Unloaded T(1rho) and T(2) in the middle and inner zones of the lateral
      anterior horn and outer zone of the medial posterior horn were significantly
      higher in OA and suggest that meniscal OA change occurs unevenly. Zonal T(1rho)
      and T(2) showed differing patterns between anterior and posterior horns,
      suggesting differences in macromolecular organization. Significant increases with
      loading were seen largely in the T(2) of controls and less frequently in subjects
      with OA. In the medial posterior horn, T(1rho) and T(2) decreased with loading in
      OA but changed negligibly in controls; these significantly different loading
      responses between groups may indicate load transmission failure in OA menisci.

PMID- 26223432
TI  - Could a sugar tax help combat obesity?

PMID- 26223431
TI  - The Impact of Certificate-of-Need Laws on Nursing Home and Home Health Care
      Expenditures.
AB  - Over the past two decades, nursing homes and home health care agencies have been
      influenced by several Medicare and Medicaid policy changes including the adoption
      of prospective payment for Medicare-paid postacute care and Medicaid-paid long
      term home and community-based care reforms. This article examines how spending
      growth in these sectors was affected by state certificate-of-need (CON) laws,
      which were designed to limit the growth of providers and have remained unchanged
      for several decades. Compared with states without CON laws, Medicare and Medicaid
      spending in states with CON laws grew faster for nursing home care and more
      slowly for home health care. In particular, we observed the slowest growth in
      community-based care in states with CON for both the nursing home and home health
      industries. Thus, controlling for other factors, public postacute and long-term
      care expenditures in CON states have become dominated by nursing homes. 

PMID- 26223434
TI  - Prolonged remission in Caucasian patients with SLE: prevalence and outcomes.
AB  - AIM: To assess the prevalence of prolonged remission in Caucasian patients
      affected with systemic lupus erythematosus (SLE) and its relationship with damage
      accrual. METHODS: Caucasian patients diagnosed with SLE between 1990 and 2009 and
      quarterly seen from 2009 to 2013 were included in the study. We defined remission
      as prolonged when lasting >=5 consecutive years. Three levels of remission were
      defined using the SLE Disease Activity Index-2000 (SLEDAI-2K): complete
      remission: no disease activity in corticosteroid-free and immunosuppressant-free
      patients; clinical remission off corticosteroids: serologically active clinical
      quiescent (SACQ) disease in corticosteroid-free patients and clinical remission
      on corticosteroids: SACQ disease in patients taking prednisone 1-5 mg/day. Damage
      was measured by the SLICC/American College of Rheumatology Damage Index (SDI).
      RESULTS: 224 patients fulfilled inclusion criteria: 196 (87.5%) were women,
      mean+/-SD disease duration 11.2+/-6.8 years. During the 5-year follow-up, 16
      patients (7.1%) achieved prolonged complete remission, 33 (14.7%) prolonged
      clinical remission off corticosteroids and 35 (15.6%) prolonged clinical
      remission on corticosteroids. At the multivariate analysis, vasculitis (OR 4.95),
      glomerulonephritis (OR 2.38) and haematological manifestations (OR 2.19) over the
      patients' disease course were associated with an unremitted disease. SDI
      increased more frequently in unremitted (72/140, 51.4%) than in remitted patients
      (22/84, 26.2%; p=0.001); SDI median increase was higher in unremitted than in
      remitted patients: 1 (0-3) vs 0 (0-2), respectively (p<0.001). At multivariate
      analysis, unremitted disease (OR 2.52) and high-dose corticosteroid intake (OR
      2.35) were risk factors for damage accrual. CONCLUSIONS: Thirty-seven percent of
      our Caucasian patients achieved a prolonged remission, which was associated with
      a better outcome in terms of damage accrual.

PMID- 26223435
TI  - Melanoma: summary of NICE guidance.

PMID- 26223433
TI  - FSD-C10: A more promising novel ROCK inhibitor than Fasudil for treatment of CNS
      autoimmunity.
AB  - Rho-Rho kinase (Rho-ROCK) triggers an intracellular signalling cascade that
      regulates cell survival, death, adhesion, migration, neurite outgrowth and
      retraction and influences the generation and development of several neurological
      disorders. Although Fasudil, a ROCK inhibitor, effectively suppressed
      encephalomyelitis (EAE), certain side effects may limit its clinical use. A novel
      and efficient ROCK inhibitor, FSD-C10, has been explored. In the present study,
      we present chemical synthesis and structure of FSD-C10, as well as the
      relationship between compound concentration and ROCK inhibition. We compared the
      inhibitory efficiency of ROCKI and ROCK II, the cell cytotoxicity, neurite
      outgrowth and dendritic formation, neurotrophic factors and vasodilation between
      Fasudil and FSD-C10. The results demonstrated that FSD-C10, like Fasudil, induced
      neurite outgrowth of neurons and dendritic formation of BV-2 microglia and
      enhanced the production of neurotrophic factor brain-derived neurotrophic factor
      (BDNF), glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT
      3). However, the cell cytotoxicity and vasodilation of FSD-C10 were relatively
      small compared with Fasudil. Although Fasudil inhibited both ROCK I and ROCK II,
      FSD-C10 more selectively suppressed ROCK II, but not ROCK I, which may be related
      to vasodilation insensitivity and animal mortality. Thus, FSD-C10 may be a safer
      and more promising novel ROCK inhibitor than Fasudil for the treatment of several
      neurological disorders.

PMID- 26223436
TI  - A Phase I study of MEDI-575, a PDGFRalpha monoclonal antibody, in Japanese
      patients with advanced solid tumors.
AB  - PURPOSE: MEDI-575 is a fully human monoclonal antibody that selectively binds to
      platelet-derived growth factor receptor alpha (PDGFRalpha). This open-label Phase
      I study assessed the safety and tolerability of MEDI-575 in Japanese patients
      with advanced solid tumors. METHODS: The study comprised two parts: Part A, dose
      escalation; Part B, dose expansion in patients with hepatocellular cancer. In
      Part A, patients were enrolled into three cohorts: MEDI-575 was administered
      intravenously over a 21-day treatment cycle at doses of 9 and 15 mg/kg/week
      (cohorts 1, 2) and 35 mg/kg/3-weekly (cohort 3). In Part B, MEDI-575 25 mg/kg/3
      weekly was administered. Secondary measures included assessment of the maximum
      tolerated dose, pharmacokinetics, immunogenicity and anti-tumor activity.
      RESULTS: Ten and 12 patients were treated in Parts A and B, respectively. There
      were no dose-limiting toxicities; the maximum tolerated dose was not determined.
      Common treatment-related adverse events were fatigue (30%) and decreased appetite
      (20%) in Part A and decreased appetite (33.3%) in Part B. All treatment-related
      adverse events were grade 1 or 2 in severity. No patients discontinued MEDI-575
      because of an adverse event and there were no patient deaths due to adverse
      events. MEDI-575 binding with PDGFRalpha resulted in a dose-dependent increase in
      PDGF-AA ligand, with plateau levels observed within 2 days and sustained during
      the dosing interval. None of the patients in Part A or B experienced complete or
      partial responses to treatment. CONCLUSIONS: MEDI-575 once weekly and 3-weekly
      was well tolerated with a favorable pharmacokinetic profile in Japanese patients
      with advanced solid tumors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01102400.

PMID- 26223437
TI  - FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese
      Population.
AB  - It is well known that the human innate immune and adaptive immune response play
      important role in tuberculosis (TB) infection and progress. Emerging evidence
      shows that FOXO3 plays an important role in the human immune system. Recent
      research has shown that the FOXO3 genetic variants are associated malaria
      infection. In this study, 268 confirmed TB patients, 321 patients with latent
      tuberculosis infection (LTBI), and 475 TB-free controls were recruited; the
      single-nucleotide polymorphism (SNP) rs12212067: T > G in FOXO3 was genotyped
      using predesigned TaqMan(r) allelic discrimination assays. The results showed
      that the G allele of rs12212067 in FOXO3 was more common in health control and
      the latent TB group compared with the active TB group (p = 0.048, odds ratio (OR)
      95 % confidence intervals (CI) = 1.37 (1.00-1.89); p = 0.042, OR 95 % CI = 1.42
      (1.01-1.99), respectively); furthermore, within active TB patients, the G allele
      of rs12212067 in FOXO3 was more frequent in extra-pulmonary tuberculosis (EPTB)
      group compared to pulmonary tuberculosis (PTB) group (p = 0.035, OR 95 % CI =
      0.57 (0.33-0.97). In conclusion, this study found that rs12212067 in FOXO3 was
      associated with increased risk of active TB. The minor G allele might be a
      protection factor which was found more common in latent TB patients and healthy
      controls than active TB patients.

PMID- 26223439
TI  - Inherited metabolic disorders: prenatal diagnosis of lysosomal storage disorders.
AB  - OBJECTIVE: To offer accurate prenatal diagnosis of lysosomal storage disorders in
      early pregnancy. METHOD: Prenatal enzymatic diagnoses of Gaucher, Fabry, Pompe,
      Niemann Pick A/B, Tay Sach, Sandoff, GM1, mucoplysaccharidoses, Wolman, Krabbe,
      Metachromatic leukodystrophy and Batten diseases were made in uncultured
      chorionic villi samples by fluorometric/spectrophotometric methods. RESULTS: Of
      331 prenatal enzymatic diagnosis, 207 fetuses (67%) were normal and 124 (37%)
      were affected. The interpretation of affected, normal and carrier fetuses was
      done using their respective reference ranges as well as % enzyme activity of
      normal mean. The prenatal molecular confirmation was feasible in 43 biochemically
      diagnosed fetuses. Of the 207 normal reported fetuses, post natal enzymatic
      confirmation was done in 23 babies, clinical status of another 165 babies was
      assessed as unaffected via questionnaire on telephone and 19 were lost to follow
      up. In affected pregnancies, 123 opted for termination of which 44 were confirmed
      enzymatically after abortion. A single false positive was determined to be a
      carrier by prenatal mutation analysis and carried to term. CONCLUSION: We
      recommend uncultured chorionic villi for reliable prenatal enzymatic diagnosis of
      various lysosomal storage disorders on account of the low rate of false positive
      (0.5%) and false negative (2.2%) results.

PMID- 26223440
TI  - Australia's nutrition transition 1961-2009: a focus on fats--CORRIGENDUM.

PMID- 26223441
TI  - External iliac artery thrombosis after common iliac artery balloon occlusion
      during cesarean hysterectomy for placenta accreta in cervico-isthmic pregnancy.
AB  - Although the role of interventional radiology in the field of obstetrical
      hemorrhage has been widely reported upon recently, the rate of procedure-related
      complications has not been fully determined. We present the case of a patient who
      developed an external iliac artery thrombosis, a rarely reported complication
      associated with prophylactic common iliac artery balloon occlusion (CIABO). After
      CIABO, we found that the dorsalis pedis artery of the right foot was weak and the
      foot was cold, despite the fact that the patient had no complaints. Computed
      tomography demonstrated a linear thrombus in the right external iliac artery. We
      managed the patient conservatively using a heparin drip without the need for
      thromboembolectomy. Our experience suggests that it is important to consider the
      risk of thrombosis formation after CIABO. Physical examination post-procedure is
      key to identifying this complication early. 

PMID- 26223442
TI  - N-Heterotriangulenes: Fascinating Relatives of Triphenylamine.
AB  - Carbonyl- and dimethylmethylene-bridged triphenylamines called N
      heterotriangulenes are not only aesthetically pleasing pi-conjugated scaffolds
      interesting on their own but also provide numerous possibilities for further
      synthetic modifications to serve as versatile precursors for the construction of
      functional organic molecules. In this Personal Account we give a historical
      synopsis depicting the long way from the initial synthesis of N
      heterotriangulenes back in the 1970s to their derivatization followed by recent
      applications in organic electronics. As a part of our ongoing research on
      heteroatom-doped pi-conjugated scaffolds we provide an overview of our synthetic
      efforts involving the N-heterotriangulene scaffolds and discuss the
      optoelectronic, redox, and self-assembly properties of the resulting molecular
      entities. 

PMID- 26223443
TI  - Metaproteomics of aquatic microbial communities in a deep and stratified estuary.
AB  - Here we harnessed the power of metaproteomics to assess the metabolic diversity
      and function of stratified aquatic microbial communities in the deep and
      expansive Lower St. Lawrence Estuary, located in eastern Canada. Vertical
      profiling of the microbial communities through the stratified water column
      revealed differences in metabolic lifestyles and in carbon and nitrogen
      processing pathways. In productive surface waters, we identified heterotrophic
      populations involved in the processing of high and low molecular weight organic
      matter from both terrestrial (e.g. cellulose and xylose) and marine (e.g. organic
      compatible osmolytes) sources. In the less productive deep waters, chemosynthetic
      production coupled to nitrification by MG-I Thaumarchaeota and Nitrospina
      appeared to be a dominant metabolic strategy. Similar to other studies of the
      coastal ocean, we identified methanol oxidation proteins originating from the
      common OM43 marine clade. However, we also identified a novel lineage of methanol
      oxidizers specifically in the particle-rich bottom (i.e. nepheloid) layer.
      Membrane transport proteins assigned to the uncultivated MG-II Euryarchaeota were
      also specifically detected in the nepheloid layer. In total, these results
      revealed strong vertical structure of microbial taxa and metabolic activities, as
      well as the presence of specific "nepheloid" taxa that may contribute
      significantly to coastal ocean nutrient cycling. 

PMID- 26223444
TI  - Preparation, characterization and properties of four new trivalent lanthanide
      complexes constructed using 2-bromine-5-methoxybenzoic acid and 1,10
      phenanthroline.
AB  - Four dinuclear trivalent lanthanide complexes of the general formula [Ln2(2-Br-5
      MOBA)6(phen)2] (Ln = Nd(), Sm(), Ho(), Er(); 2-Br-5-MOBA = 2-bromine-5
      methoxybenzoate, phen = 1,10-phenanthroline) were prepared and structurally
      characterized. The complexes to are isostructural with a coordination number of
      nine. The carboxylic acid ligands adopt bridging, bidentate chelating, and
      tridentate chelating bridging modes to coordinate with Ln(iii) ions. The
      structures of the complexes were confirmed on the basis of elemental analysis,
      molar conductance, thermogravimetric analysis (TGA), and IR and UV spectra. The
      heat capacities and thermal circulating processes of the prepared complexes were
      performed on a differential scanning calorimeter under a nitrogen atmosphere. Two
      remarkable solid-solid phase transitions existed both in the heat capacities and
      thermal circulating processes. The bacteriostatic activities of the complexes
      were evaluated against Candida albicans, Escherichia coli and Staphylococcus
      aureus. Besides, the luminescent property of complex was also investigated, and
      the magnetic properties of complexes and were also discussed in detail. 

PMID- 26223445
TI  - [Use of ECMO in adult patients with cardiogenic shock: a position paper of the
      Austrian Society of Cardiology].
AB  - The use of ECMO to stabilize critically ill patients with severely depressed
      cardiac function and hemodynamics increased in the last years due to broader
      availability, better performance and easier implantation of the devices. The
      present guidelines of the Austrian Society of Cardiology focus on the use of ECMO
      in adult non-operated patients with cardiac diseases. Not only indications and
      contraindications are highlighted, but also the equally important issues of
      monitoring, complication management, measures during implantation and operation,
      and weaning of the devices are treated in detail. Thereby the present guidelines
      aim to optimize the use of ECMO in the individual centers, and aim to help
      current non-ECMO centers in developing a local ECMO-program or to contact ECMO
      centers for discussion of individual patients. 

PMID- 26223446
TI  - Evaluating whole transcriptome amplification for gene profiling experiments using
      RNA-Seq.
AB  - BACKGROUND: RNA-Seq has enabled high-throughput gene expression profiling to
      provide insight into the functional link between genotype and phenotype. Low
      quantities of starting RNA can be a severe hindrance for studies that aim to
      utilize RNA-Seq. To mitigate this bottleneck, whole transcriptome amplification
      (WTA) technologies have been developed to generate sufficient sequencing targets
      from minute amounts of RNA. Successful WTA requires accurate replication of
      transcript abundance without the loss or distortion of specific mRNAs. Here, we
      test the efficacy of NuGEN's Ovation RNA-Seq V2 system, which uses linear
      isothermal amplification with a unique chimeric primer for amplification, using
      white adipose tissue from standard laboratory rats (Rattus norvegicus). Our goal
      was to investigate potential biological artifacts introduced through WTA
      approaches by establishing comparisons between matched raw and amplified RNA
      libraries derived from biological replicates. RESULTS: We found that 93% of
      expressed genes were identical between all unamplified versus matched amplified
      comparisons, also finding that gene density is similar across all comparisons.
      Our sequencing experiment and downstream bioinformatic analyses using the Tuxedo
      analysis pipeline resulted in the assembly of 25,543 high-quality transcripts.
      Libraries constructed from raw RNA and WTA samples averaged 15,298 and 15,253
      expressed genes, respectively. Although significant differentially expressed
      genes (P < 0.05) were identified in all matched samples, each of these represents
      less than 0.15% of all shared genes for each comparison. CONCLUSIONS:
      Transcriptome amplification is efficient at maintaining relative transcript
      frequencies with no significant bias when using this NuGEN linear isothermal
      amplification kit under ideal laboratory conditions as presented in this study.
      This methodology has broad applications, from clinical and diagnostic, to field
      based studies when sample acquisition, or sample preservation, methods prove
      challenging.

PMID- 26223447
TI  - Recency and frequency of HIV testing among men who have sex with men in Germany
      and socio-demographic factors associated with testing behaviour.
AB  - BACKGROUND: Testing for presence of HIV infection is a pre-requisite to qualify
      for antiretroviral treatment. A considerable proportion of German men who have
      sex with men (MSM) infected with HIV have a CD4 cell count below 350 cells/MUl at
      time of diagnosis and are thus defined as "late presenters". Late presentation
      increases the risk of adverse disease outcomes. In addition, knowledge and
      assessment of HIV status is often used for decisions about condom use and anal
      intercourse with steady and non-steady partners. Incorrect assumptions may result
      in high risk for HIV transmission. METHODS: Between 11/2013 and 01/2014 MSM were
      recruited to an online survey predominantly by personalized invitation messages
      from MSM social networking and dating websites. Respondents were asked about
      demographic characteristics, HIV testing history, reasons for testing decisions,
      and sexual behaviours. We describe reasons for not testing and analyse factors
      associated with not or infrequent testing using univariable and multivariable
      multinomial regression. RESULTS: Questions on HIV testing history were answered
      by 15,297 respondents. An HIV test within the last 12 months was reported by 38%,
      a test more than 12 months ago by 27% and 35% had never been tested for HIV.
      Compared to recently tested, respondents who had never tested were more likely to
      be younger than 25 years (adjusted relative risk ratio (aRRR) 2.90, 95% CI 2.11
      3.99), living in a settlement with less than 100,000 inhabitants (aRRR 1.47, 95%
      CI 1.18-1.83), being less open about their sexual orientation to their co
      workers/classmates, and particularly to their primary care provider (aRRR 4.54,
      95% CI 4.02-5.11). Untested and less frequently tested respondents reported less
      sex partners and a lower proportion reported unprotected anal intercourse (UAI)
      with a non-steady partner (24% compared to 38% among those recently tested).
      CONCLUSIONS: MSM who were younger, who did not live in large cities, and who were
      not out about their sexual orientation tested less frequently for HIV. Apart from
      strengthening protection from sexual orientation-related discrimination and
      empowering MSM who conceal their orientation, more opportunities to test
      anonymously and without revealing one's sexual orientation should be provided.

PMID- 26223449
TI  - Reversible sol-gel transitions of aqueous dispersions of silica nanoparticles
      grafted with diblock copolymer brushes composed of a thermosensitive inner block
      and a charged outer block.
AB  - We report in this article that aqueous dispersions of thermosensitive diblock
      copolymer brush-grafted 17 nm silica nanoparticles (hairy NPs) can undergo in
      situ, reversible sol-gel transitions in response to temperature changes. The
      brushes consisted of a thermosensitive poly(methoxydi(ethylene glycol)
      methacrylate) (PDEGMMA) inner block and a charge-carrying, poly(DEGMMA-co-2
      (methacryloyloxy)ethyltrimethylammonium iodide) outer block, which were prepared
      by a one-pot, surface-initiated atom transfer radical polymerization and
      subsequent quaternization of tertiary amine moieties in the second block with
      iodomethane. Above a critical concentration, the aqueous dispersion of hairy NPs
      with an appropriate block copolymer composition exhibited a reversible transition
      from a free flowing liquid to a free standing hydrogel upon cooling from elevated
      temperatures, which was driven by the lower critical solution temperature
      transition of the thermosensitive inner block of hairy NPs as confirmed by
      dynamic light scattering study. At the same concentration of hairy NPs, the sol
      gel transition temperature was higher when the highly hydrated, charged outer
      block was longer. The transition temperature decreased with decreasing the
      concentration of hairy NPs in the dispersion; reversible gelation was achieved
      with a concentration of hairy NPs in water as low as 5.5 wt%. Interestingly, the
      LCST transition of the inner thermosensitive PDEGMMA block disappeared and no sol
      gel transition was observed in the studied temperature range when the charged
      outer block was sufficiently long. 

PMID- 26223448
TI  - Recurrent candida prosthetic endocarditis over fifteen years managed with medical
      therapy and four valvular surgeries: a case report and review of literature.
AB  - BACKGROUND: Candida prosthetic endocarditis (CPE) is an uncommon disease
      involving less than 1 % of infective endocarditis patients and associated with
      high recurrence rate. Immunosuppresion, intravenous drug abuse, cardiac surgery
      and indwelling foreign bodies are the major risk factors for CPE. There are very
      few reported cases of CPE where more than one surgery was performed and there has
      generally been limited follow up on these cases. CASE PRESENTATION: We report a
      case of a 35 year old woman who had mitral valve annuloplasty complicated by
      recurrent episodes of CPE leading to multiple mitral valve replacements (MVR).
      She underwent MVR surgeries a total of four times over an eighteen year period
      and had good functionality during most of this time while being on antifungal
      suppressive treatment. This is a unique case in terms of numbers of surgeries
      performed, the length of the follow up and the involvement of three different
      Candida species. CONCLUSION: Current guidelines for the treatment of candida
      endocarditis recommend surgical treatment followed by long term antifungal
      therapy although the cure rate by all treatments is low. However we feel that
      based on this one case it is reasonable to consider multiple redo valve
      replacement surgeries in conjunction with antifungal treatment for selected
      patients stable enough to tolerate the surgery.

PMID- 26223450
TI  - Implications for changes in Anopheles darlingi biting behaviour in three
      communities in the peri-Iquitos region of Amazonian Peru.
AB  - BACKGROUND: Malaria transmission in the peri-Iquitos region of Amazonian Peru has
      been designated as seasonal and hypo-endemic with recently described hyper
      endemic hotspots. Despite relatively recent distribution of long-lasting
      insecticidal bed nets (LLINs), malaria in Amazonian Peru persists and increased
      substantially in 2014 compared to previous years. Anopheles darlingi, identified
      as the main malaria vector, is known for its variable behaviour depending on
      locality and environment. METHODS: To evaluate vector biology metrics in relation
      to seasonality and malaria transmission, mosquito collections were carried out in
      three localities in the peri-Iquitos region, Loreto, Peru in 2011-2012. Human
      landing catch (HLC) collection method, Shannon (SHA) and CDC trap types were
      compared for effectiveness in a neotropical setting. Abundance, human biting rate
      and entomological inoculation rate (EIR) were measured to provide an updated view
      of transmission patterns post-LLIN distribution. RESULTS: HLC collected
      significantly more anopheline mosquitoes than SHA and CDC light traps. Anopheles
      darlingi was the most prevalent species in all three villages (84% overall).
      Biting patterns varied depending on trap type, season and village. EIR varied
      temporally (monthly) and spatially and the highest (2.52) occurred during the
      2012 malaria outbreak in Cahuide. Unexpectedly there was a high infection rate
      (1.47 and 1.75) outside the normal malaria transmission season, coincident with a
      second local outbreak in Cahuide. The first identification of Anopheles dunhami
      and Anopheles oswaldoi C in Peru, using molecular markers, is also reported in
      this study. CONCLUSION: These data underscore the importance of HLC as the most
      meaningful collection method for measuring vector biology indices in this region.
      The highest monthly EIR provides additional evidence of seasonal transmission in
      riverine localities correlated with high river levels, and An. darlingi as the
      only contributor to transmission. The trend of an increase in outdoor-biting
      together with early-evening infected mosquitoes may undermine the effectiveness
      of LLINs as a primary malaria intervention.

PMID- 26223452
TI  - Mental health issues and discrimination among older LGBTI people.
AB  - LGBT is an acronym used to describe people from diverse sexual orientation or
      gender identity, people that are gay, lesbian, bisexual, or transgender. LGBT
      people do not constitute a single group nor does each individual "group"
      constitute a homogeneous unity. However, as higher rates of depression and/or
      anxiety have been observed in older LGBT people, compared to their heterosexual
      counterparts (Guasp, 2011) there is a need to raise the profile of mental health
      issues amongst these groups. The additional letter I is also often included in
      the acronym LGBTI as intersex people are often included as another gender diverse
      group. However, there is very little research that includes intersex people and
      none on older intersex people's mental health so this editorial is restricted to
      consideration of older LGBT people. 

PMID- 26223451
TI  - 'Candidatus Phytoplasma phoenicium' associated with almond witches'-broom
      disease: from draft genome to genetic diversity among strain populations.
AB  - BACKGROUND: Almond witches'-broom (AlmWB), a devastating disease of almond, peach
      and nectarine in Lebanon, is associated with 'Candidatus Phytoplasma phoenicium'.
      In the present study, we generated a draft genome sequence of 'Ca. P. phoenicium'
      strain SA213, representative of phytoplasma strain populations from different
      host plants, and determined the genetic diversity among phytoplasma strain
      populations by phylogenetic analyses of 16S rRNA, groEL, tufB and inmp gene
      sequences. RESULTS: Sequence-based typing and phylogenetic analysis of the gene
      inmp, coding an integral membrane protein, distinguished AlmWB-associated
      phytoplasma strains originating from diverse host plants, whereas their 16S rRNA,
      tufB and groEL genes shared 100 % sequence identity. Moreover, dN/dS analysis
      indicated positive selection acting on inmp gene. Additionally, the analysis of
      'Ca. P. phoenicium' draft genome revealed the presence of integral membrane
      proteins and effector-like proteins and potential candidates for interaction with
      hosts. One of the integral membrane proteins was predicted as BI-1, an inhibitor
      of apoptosis-promoting Bax factor. Bioinformatics analyses revealed the presence
      of putative BI-1 in draft and complete genomes of other 'Ca. Phytoplasma'
      species. CONCLUSION: The genetic diversity within 'Ca. P. phoenicium' strain
      populations in Lebanon suggested that AlmWB disease could be associated with
      phytoplasma strains derived from the adaptation of an original strain to diverse
      hosts. Moreover, the identification of a putative inhibitor of apoptosis
      promoting Bax factor (BI-1) in 'Ca. P. phoenicium' draft genome and within
      genomes of other 'Ca. Phytoplasma' species suggested its potential role as a
      phytoplasma fitness-increasing factor by modification of the host-defense
      response.

PMID- 26223453
TI  - A useful development in measuring activities of daily living.

PMID- 26223454
TI  - Impact of Screening for Hepatic Hemangiomas in Patients with Multiple Cutaneous
      Infantile Hemangiomas.
AB  - OBJECTIVES: Hepatic hemangiomas are often found in association with multiple
      cutaneous infantile hemangiomas. Screening abdominal ultrasonography has been
      recommended for patients with five or more cutaneous lesions. We sought to
      determine whether hemangiomas found through screening had improved clinical
      outcomes. METHODS: Patients entered into our hepatic hemangioma registry between
      1995 and 2012 were reviewed. RESULTS: Seventy-two patients with multiple
      cutaneous and hepatic hemangiomas were identified; 43 (60%) were detected through
      screening. The median age at diagnosis was 41 days for screened patients and 53
      days for those not screened. Screening detected 40 (93%) multifocal and 3 (7%)
      diffuse hemangiomas, compared to 18 (62%) and 11 (38%), respectively, in the
      nonscreened group. Patients identified by screening had lower incidences of
      congestive heart failure and hypothyroidism and were less likely to receive
      treatment for their hemangiomas. The mortality rate in the children not screened
      was 28% (n = 8). None of the patients found by screening died (p < 0.001).
      Multivariate analysis of treated patients demonstrated that screening was a
      significant predictor of reduced mortality (p = 0.04). CONCLUSION: Hepatic
      hemangiomas found through screening ultrasonography are less likely to develop
      serious clinical sequelae. Although the reasons for this may include detection of
      hemangiomas that are less likely to progress to symptomatic disease, it appears
      that it also allows for earlier intervention for more concerning (e.g. diffuse)
      subtypes. Screening may allow for closer surveillance and earlier treatment
      before life-threatening progression in a subset of infants with liver
      hemangiomas, preventing complications and reducing mortality.

PMID- 26223455
TI  - Keeping a child's donor sperm conception secret is not linked to family and child
      functioning during middle childhood: An Australian comparative study.
AB  - BACKGROUND AND AIM: Controversy exists as to whether children conceived using
      donor sperm should be told about their origins and the possible deleterious
      effects of secrecy. MATERIALS AND METHODS: The Follow-Up of Children Conceived
      through Donor Insemination research compares 'family functioning' and 'child well
      being' in 62 families where donor-conceived children aged between 5 and 13 years
      had been 'told' (N = 29) and 'not told' (N = 33) of their genetic heritage.
      Couples were treated through the Prince Henry's Institute of Medical Research
      Reproductive Medicine Clinic. Standardised measures of family functioning and
      child well-being collected from mothers were modelled to estimate mean
      differences according to knowledge of conception. RESULTS: Mean differences
      between the two 'knowledge of conception' groups were generally very small and
      not statistically significant; adjustment for covariates did not make a
      substantive difference to the interpretation of group differences. Scores on
      family functioning and child well-being measures were within normal limits for
      both the 'told' and 'not told' groups. CONCLUSION: Further research on parents'
      experiences would usefully inform discussion on the forms of education and
      support that would encourage parents to engage with the issues of disclosure and
      nondisclosure, and promote transparency as well as societal awareness, acceptance
      and understanding of this method of family formation.

PMID- 26223456
TI  - Corrigendum: "Turn on" and label-free core-shell Ag@SiO2 nanoparticles-based
      metal-enhanced fluorescent (MEF) aptasensor for Hg(2+).

PMID- 26223457
TI  - Crunchiness Loss and Moisture Toughening in Puffed Cereals and Snacks.
AB  - Upon moisture uptake, dry cellular cereals and snacks loose their brittleness and
      become soggy. This familiar phenomenon is manifested in smoothing their
      compressive force-displacement curves. These curves' degree of jaggedness,
      expressed by their apparent fractal dimension, can serve as an instrumental
      measure of the particles' crunchiness. The relationship between the apparent
      fractal dimension and moisture content or water activity has a characteristic
      sigmoid shape. The relationship between the sensorily perceived crunchiness and
      moisture also has a sigmoid shape whose inflection point lies at about the same
      location. The transition between the brittle and soggy states, however, appears
      sharper in the apparent fractal dimension compared with moisture plot. Less
      familiar is the observation that at moderate levels of moisture content, while
      the particles' crunchiness is being lost, their stiffness actually rises, a
      phenomenon that can be dubbed "moisture toughening." We show this phenomenon in
      commercial Peanut Butter Crunch(r) (sweet starch-based cereal), Cheese Balls
      (salty starch-based snack), and Pork Rind also known as "Chicharon" (salty deep
      fried pork skin), 3 crunchy foods that have very different chemical composition.
      We also show that in the first 2 foods, moisture toughening was perceived
      sensorily as increased "hardness." We have concluded that the partial
      plasticization, which caused the brittleness loss, also inhibited failure
      propagation, which allowed the solid matrix to sustain higher stresses. This can
      explain other published reports of the phenomenon in different foods and model
      systems. 

PMID- 26223458
TI  - Does Chondrocalcinosis Associate With a Distinct Radiographic Phenotype of
      Osteoarthritis in Knees and Hips? A Case-Control Study.
AB  - OBJECTIVE: To examine if knee chondrocalcinosis (CC), hip CC, or CC at distant
      joints associates with a distinct radiographic phenotype of osteoarthritis (OA)
      in knees or hips. METHODS: We conducted a case-control study using data from the
      Genetics of Osteoarthritis and Lifestyle (GOAL) study (n = 3,170). All
      participants of the GOAL study had radiographs of knees, hands, and pelvis, which
      have been scored for CC and for individual radiographic features of OA. For this
      study, cases had radiographic OA and CC, and controls had radiographic OA without
      CC at the index joint. Data for knees and hips were analyzed separately. Binary
      logistic regression was used to examine the association between each radiographic
      phenotype and CC in joints with OA. Generalized estimating equation analysis was
      used to account for correlated data. RESULTS: Knee CC, and CC at any distant
      joint (without knee CC), associated with attrition in knee OA (adjusted odds
      ratio 2.32 [95% confidence interval 1.42-3.79] and 2.42 [1.41-4.13],
      respectively). There was no association between knee CC and osteophytosis or
      joint space narrowing (JSN) in knees with OA. Hip CC associated negatively with
      the summated osteophyte score and minimum JSN in hip OA. However, in hips with
      OA, CC did not associate with cysts or sclerosis. Additionally, distant joint CC
      did not associate with any structural change in hip OA. CONCLUSION: This study
      demonstrates that knee CC and CC at distant joints associate with attrition in
      knee OA, and hip CC associates with a milder hip OA phenotype. There was no
      evidence that CC associates with a hypertrophic OA phenotype.

PMID- 26223459
TI  - SMN deficiency disrupts gastrointestinal and enteric nervous system function in
      mice.

PMID- 26223460
TI  - Identification of the possible new odor-active compounds "12-methyltridecanal and
      its analogs" responsible for the characteristic aroma of ripe Gouda-type cheese.
AB  - The aroma concentrates of the three maturation stages of Gouda-type cheeses were
      prepared by combining the solvent extraction and the solvent assisted flavor
      evaporation techniques. The aroma extract dilution analysis applied to the
      volatile fraction revealed 31 odorants that were identified or tentatively
      identified from the 38 odor-active peaks with FD factors between 4(3) and 4(8).
      By comparison with the FD factors in the three maturation stages of the cheeses,
      16 odorants, including 12-methyltridecanal, which is a newly identified odorant
      from the cheese, increased with the increasing maturation stage of the cheese. In
      addition, many iso- and anteiso-methyl-branched long-chain aliphatic aldehydes
      could be identified as the analogs of 12-methyltridecanal, which have a unique
      odor note. It may be then expected that these aldehydes were able to influence
      the flavor of the highly ripened Gouda cheese, since these compounds also
      increased with the increasing maturation stage. 

PMID- 26223462
TI  - HPTLC Determination of Three Gliptins in Binary Mixtures with Metformin.
AB  - A single, simple, selective and validated high performance thin layer
      chromatographic (HPTLC) method was developed for the determination of either
      linagliptin (LGP), saxagliptin (SGP) or vildagliptin (VGP) in their binary
      mixtures with metformin (MET) in pharmaceutical preparations using
      environmentally preferable green mobile phase system. Separation was carried out
      on Merck HPTLC aluminum sheets of silica gel 60 F254 using methanol-0.5% w/v
      aqueous ammonium sulfate (8 : 2, v/v) as mobile phase. Densitometric measurement
      of the spots was performed at 225 nm for LGP/MET mixture and at 208 nm for both
      SGP/MET and VGP/MET mixtures. The linear regression analysis data were used for
      the regression line in the range of 0.05-0.5 ug/band for LGP and SGP and 0.2-2
      and 5-40 ug/band for VGP and MET, respectively. The method was validated and
      showed good performances in terms of linearity, limits of detection and
      quantitation, precision, accuracy, selectivity and specificity. The calculated
      percentage relative error values and percentage relative standard deviation for
      intra- and interday precision studies did not exceed 2%. The developed method was
      satisfactorily applied for the analysis of pharmaceutical preparations and proved
      to be specific and accurate for the quality control of the cited drugs in their
      dosage forms. 

PMID- 26223461
TI  - Microenvironment-related biomarkers and novel targets in classical Hodgkin's
      lymphoma.
AB  - Classical Hodgkin's lymphoma accounts for approximately 10% of all malignant
      lymphomas. Although most patients can be cured with modern treatment strategies,
      approximately 25% of them experience either primary or secondary
      chemorefractoriness or disease relapse, thus requiring novel treatments.
      Increasing preclinical and clinical evidences have demonstrated the role of
      microenvironment in the molecular pathogenesis of classical Hodgkin's lymphoma
      and elucidated the complex cross-talk between the malignant Hodgkin Reed
      Sternberg cells and the nonmalignant, reactive cells of the microenvironment,
      strongly supporting novel therapeutic approaches aimed at targeting Hodgkin's
      Reed-Sternberg cells along with reactive cells in order to overcome
      chemorefractoriness. In the near future, these novel therapies will also be
      tested in chemosensitive patients to reduce long-term toxicities of chemo
      radiotherapy. 

PMID- 26223463
TI  - HILIC-MS Determination of Genotoxic Impurity of 2-Chloro-N-(2
      Chloroethyl)Ethanamine in the Vortioxetine Manufacturing Process.
AB  - In the last decade, pharmaceutical regulatory agencies are focused on monitoring
      and evaluation of trace-level genotoxic impurities (GTIs) in drug substances,
      which requires manufacturers to deliver innovative approaches for their analysis
      and control. GTIs in the low p.p.m. level rising from the process of drug
      production have to be positively identified and quantified. Therefore, sensitive
      and selective analytical methods are necessary for required quantification level
      of these GTIs. Unfortunately, general guidance on how to develop strategy of the
      analysis and control of GTIs is currently missing in the pharmaceutical industry.
      Therefore, practical example of the analytical control of 2-chloro-N-(2
      chloroethyl)ethanamine GTI in the vortioxetine (VOR) manufacturing process was
      demonstrated in this work. QDa mass detection with electrospray ionization in
      selected-ion recording mode was utilized for quantitation of GTIs. The method of
      hydrophilic interaction liquid chromatography coupled with mass spectrometry
      detection (HILIC-MS) was validated as per International Conference on
      Harmonization guidelines and was able to quantitate GTIs at 75 p.p.m. with
      respect to VOR. The HILIC-MS method was achieved using a Primesep B column (150 *
      4.6 mm, 5.0 um; Sielc, USA) using mobile phase consisting of 10 mM ammonium
      formate buffer pH 3.0 and acetonitrile (5 : 95, v/v) at 0.8 mL/min flow rate. The
      QDa mass detector was operated in the positive ion mode. Quadrupole mass analyzer
      was employed in selected-ion monitoring mode using target ion at m/z 142 as
      [M+H](+). 

PMID- 26223464
TI  - A 1,1-Carboboration Route to Bora-Nazarov Systems.
AB  - Hydroboration of the conjugated enynes 1 a and 1 b with Piers' borane [HB(C6F5)2]
      gave the respective dienylboranes trans-2 c and trans-2 d. Their photolysis
      resulted in the formation of the dihydroborole products 3 c and 3 d. Both were
      converted to their pyridine adducts 5 c and 5 d, respectively. Compounds 3 c and
      5 c,d were characterized by X-ray diffraction. The reaction of the
      bis(enynyl)boranes 6 a and 6 b with B(C6F5)3 resulted in the formation of the
      dihydroboroles 7 a and 7 b, respectively. This reaction is thought to proceed by
      1,1-carboboration of one of the enynyl substituents at boron to generate the
      dienylborane intermediates 8 a/8 b, followed by thermally induced bora-Nazarov
      ring-closure and subsequent stabilizing 1,2-pentafluorophenyl group migration
      from boron to carbon. Compound 7 a was characterized by X-ray diffraction and
      solid-state (11)B NMR spectroscopy.

PMID- 26223465
TI  - Asymmetric cyclopropanation of conjugated cyanosulfones using a novel cupreine
      organocatalyst: rapid access to delta(3)-amino acids.
AB  - An organocatalytic asymmetric synthesis of a novel, highly functionalised
      cyclopropane system furnished with versatile substituents and containing a
      quaternary centre is described. The process utilises a new bifunctional catalyst
      based on the cinchona alkaloid framework and the products made using this
      catalyst were obtained as single diastereoisomers, with very high
      enantioselectivities (up to 96% ee). We have also demonstrated that these
      resulting cyclopropanes are very useful synthetic intermediates to interesting
      products, such as the difficult to access delta(3)-amino acids. 

PMID- 26223466
TI  - Intermediate outcomes of rheumatic mitral stenosis post-balloon mitral valvotomy.
AB  - BACKGROUND: Balloon mitral valvotomy is a standard therapeutic modality for
      managing rheumatic mitral stenosis. Data on intermediate outcomes of this
      procedure are limited. Thus we investigated the intermediate outcome after
      balloon mitral valvotomy performed at a large tertiary center in India. METHODS:
      Case records and follow-up data of 2330 patients who underwent valvotomy from
      June 1999 to December 2005 were retrieved from the hospital information system
      and analyzed. RESULTS: The median age of the patients was 32 +/- 11 years, 1363
      were female including 36 who were pregnant, and 379 were in atrial fibrillation.
      Follow-up ranged from 1 to 14 years (mean 4.5 years, median 4.0 years). The
      procedural success rate was 93%. Atrial fibrillation, higher functional class,
      and worse valve morphology were independent predictors of a poor procedural
      outcome. Patients with sinus rhythm had better event-free survival (10.43 years,
      95% confidence interval: 10.1-10.7) compared to those with atrial fibrillation
      (8.17 years, 95% confidence interval: 7.5-8.8). Patients who achieved a valve
      area >1.75 cm(2) had a better event-free survival (11.7 years, 95% confidence
      interval: 11.4-12.0) than those with a valve area of 1.5-1.74 cm(2) (9.3 years,
      95% confidence interval: 9.0-9.7). On multivariate analysis, higher functional
      class, worse valve morphology, and new significant mitral regurgitation were
      predictors of a poor outcome. Achieved mitral valve area >1.75 cm(2) was an
      independent predictor of a good outcome. CONCLUSION: Patients with sinus rhythm,
      less gross valve deformity, and a post-balloon mitral valvotomy area >1.75 cm(2)
      had better intermediate outcomes.

PMID- 26223467
TI  - Rescue surgery for neonate with huge rhabdomyoma and left outflow obstruction.
AB  - We describe a rescue operation in a neonate with a large left ventricular tumor
      obstructing the left ventricular outflow tract. Surgical resection was performed
      through an aortotomy and transseptal approach. We excised the main part of the
      tumor, which was obstructing the outflow tract, leaving a portion that was
      strongly attached to posterior wall of the left ventricle and mitral valve
      annulus, which was not feasible to remove. Histological examination showed a
      rhabdomyoma with benign features. The girl was doing well after 3 months, with no
      residual tumor growth and no signs of obstruction of the left ventricular outflow
      tract.

PMID- 26223468
TI  - Bridging computational approaches to speech production: The semantic-lexical
      auditory-motor model (SLAM).
AB  - Speech production is studied from both psycholinguistic and motor-control
      perspectives, with little interaction between the approaches. We assessed the
      explanatory value of integrating psycholinguistic and motor-control concepts for
      theories of speech production. By augmenting a popular psycholinguistic model of
      lexical retrieval with a motor-control-inspired architecture, we created a new
      computational model to explain speech errors in the context of aphasia. Comparing
      the model fits to picture-naming data from 255 aphasic patients, we found that
      our new model improves fits for a theoretically predictable subtype of aphasia:
      conduction. We discovered that the improved fits for this group were a result of
      strong auditory-lexical feedback activation, combined with weaker auditory-motor
      feedforward activation, leading to increased competition from phonologically
      related neighbors during lexical selection. We discuss the implications of our
      findings with respect to other extant models of lexical retrieval.

PMID- 26223469
TI  - Media multitasking and memory: Differences in working memory and long-term
      memory.
AB  - Increasing access to media in the 21st century has led to a rapid rise in the
      prevalence of media multitasking (simultaneous use of multiple media streams).
      Such behavior is associated with various cognitive differences, such as
      difficulty filtering distracting information and increased trait impulsivity.
      Given the rise in media multitasking by children, adolescents, and adults, a full
      understanding of the cognitive profile of media multitaskers is imperative. Here
      we investigated the relationship between chronic media multitasking and working
      memory (WM) and long-term memory (LTM) performance. Four key findings are
      reported (1) heavy media multitaskers (HMMs) exhibited lower WM performance,
      regardless of whether external distraction was present or absent; (2) lower
      performance on multiple WM tasks predicted lower LTM performance; (3) media
      multitasking-related differences in memory reflected differences in
      discriminability rather than decision bias; and (4) attentional impulsivity
      correlated with media multitasking behavior and reduced WM performance. These
      findings suggest that chronic media multitasking is associated with a wider
      attentional scope/higher attentional impulsivity, which may allow goal-irrelevant
      information to compete with goal-relevant information. As a consequence, heavy
      media multitaskers are able to hold fewer or less precise goal-relevant
      representations in WM. HMMs' wider attentional scope, combined with their
      diminished WM performance, propagates forward to yield lower LTM performance. As
      such, chronic media multitasking is associated with a reduced ability to draw on
      the past--be it very recent or more remote--to inform present behavior.

PMID- 26223470
TI  - Erratum to: The reliability of retro-cues determines the fate of noncued visual
      working memory representations.

PMID- 26223471
TI  - Fukutin, identified by the Escherichia coli ampicillin secretion trap (CAST)
      method, participates in tumor progression in gastric cancer.
AB  - BACKGROUND: Gastric cancer (GC) is the fifth commonest malignancy worldwide and
      still one of the leading causes of cancer-related death. The aim of this study
      was to identify a novel prognostic marker or therapeutic target for GC. METHODS:
      We analyzed candidate genes from our previous Escherichia coli ampicillin
      secretion trap (CAST) libraries in detail, and focused on the FKTN gene because
      it was overexpressed in both GC cell line CAST libraries, MKN-1 and MKN-45.
      RESULTS: Quantitative reverse transcriptase PCR analysis of FKTN revealed that
      FKTN messenger RNA was overexpressed in nine of 28 (32.1 %) GC tissue samples
      compared with nonneoplastic gastric mucosa. Immunostaining of fukutin showed that
      297 of 695 cases (42.7 %) were positive for fukutin. Fukutin-positive GC cases
      were significantly associated with differentiated histological features, and
      advanced T grade and N grade. In addition, fukutin expression was observed more
      frequently in the intestinal phenotype (51 %) of GC than in other phenotypes (37
      %) when defined by the expression patterns of mucin 5AC, mucin 6, mucin 2, and
      CD10. FKTN small interfering RNA treatment decreased GC cell proliferation.
      CONCLUSIONS: These results indicate that the expression of fukutin may be a key
      regulator for progression of GC with the intestinal mucin phenotype.

PMID- 26223473
TI  - Cohort Effects in the Genetic Influence on Smoking.
AB  - We examine the hypothesis that the heritability of smoking has varied over the
      course of recent history as a function of associated changes in the composition
      of the smoking and non-smoking populations. Classical twin-based heritability
      analysis has suggested that genetic basis of smoking has increased as the
      information about the harms of tobacco has become more prevalent-particularly
      after the issuance of the 1964 Surgeon General's Report. In the present paper we
      deploy alternative methods to test this claim. We use data from the Health and
      Retirement Study to estimate cohort differences in the genetic influence on
      smoking using both genomic-relatedness-matrix restricted maximum likelihood and a
      modified DeFries-Fulker approach. We perform a similar exercise deploying a
      polygenic score for smoking using results generated by the Tobacco and Genetics
      consortium. The results support earlier claims that the genetic influence in
      smoking behavior has increased over time. Emphasizing historical periods and
      birth cohorts as environmental factors has benefits over existing GxE research.
      Our results provide additional support for the idea that anti-smoking policies of
      the 1980s may not be as effective because of the increasingly important role of
      genotype as a determinant of smoking status. 

PMID- 26223472
TI  - Comparative analysis of upper gastrointestinal endoscopy, double-contrast upper
      gastrointestinal barium X-ray radiography, and the titer of serum anti
      Helicobacter pylori IgG focusing on the diagnosis of atrophic gastritis.
AB  - BACKGROUND: Upper gastrointestinal endoscopy (UGI-ES) and double-contrast upper
      gastrointestinal barium X-ray radiography (UGI-XR) are two major image-based
      methods to diagnose atrophic gastritis, which is mostly induced by Helicobacter
      pylori infection. However, there have been few studies directly comparing them.
      METHODS: Atrophic gastritis was evaluated using the data of 962 healthy subjects
      who underwent UGI-ES and UGI-XR within 1 year. RESULTS AND CONCLUSION: Based on
      UGI-ES and UGI-XR, 602 subjects did not have atrophic gastritis and 254 subjects
      did have it. Considering UGI-ES-based atrophic gastritis as the standard,
      sensitivity and specificity of UGI-XR-based atrophic gastritis were 92.0 %
      (254/276) and 92.8 % (602/649), respectively. The seven-grade Kimura-Takemoto
      classification of UGI-ES-based atrophic gastritis showed a strong and significant
      association with the four-grade UGI-XR-based atrophic gastritis. Sensitivity and
      specificity of serum anti-Helicobacter pylori IgG to detect UGI-ES/UGI-XR-based
      atrophic gastritis were 89.4 % (227/254) and 99.8 % (601/602), indicating that
      atrophic gastritis can be overlooked according to serum anti-Helicobacter pylori
      IgG alone.

PMID- 26223474
TI  - Exploring bubble oscillation and mass transfer enhancement in acoustic-assisted
      liquid-liquid extraction with a microfluidic device.
AB  - We investigated bubble oscillation and its induced enhancement of mass transfer
      in a liquid-liquid extraction process with an acoustically-driven, bubble-based
      microfluidic device. The oscillation of individually trapped bubbles, of known
      sizes, in microchannels was studied at both a fixed frequency, and over a range
      of frequencies. Resonant frequencies were analytically identified and were found
      to be in agreement with the experimental observations. The acoustic streaming
      induced by the bubble oscillation was identified as the cause of this enhanced
      extraction. Experiments extracting Rhodanmine B from an aqueous phase (DI water)
      to an organic phase (1-octanol) were performed to determine the relationship
      between extraction efficiency and applied acoustic power. The enhanced efficiency
      in mass transport via these acoustic-energy-assisted processes was confirmed by
      comparisons against a pure diffusion-based process. 

PMID- 26223475
TI  - Increased morbidity and mortality of a concomitant colectomy during a
      pancreaticoduodenectomy: an NSQIP propensity-score matched analysis.
AB  - BACKGROUND: Select patients with peri-ampullary cancers require concomitant colon
      resection (CR) during a pancreaticoduodenectomy (PD) for margin-negative
      resections. This study analysed the impact of concomitant CR on major morbidity
      (MM) and mortality. METHODS: National Surgical Quality Improvement Program
      (NSQIP) patients undergoing PD for peri-ampullary cancers were identified from
      2005 to 2012. A 4 : 1 propensity-score matched analysis isolated the impact of CR
      upon PD. Risk factors for 30-day MM and mortality were analysed to determine post
      operative sequelae of PD+CR. RESULTS: From 10 965 PD and 159 PD+CR patients, 624
      and 156, respectively, were selected for 4 : 1 matched analysis. PD+CR resulted
      in a higher MM and mortality (50.0% and 9.0%) versus PD alone (28.8% and 2.9%,
      respectively, P < 0.001). Multivariate analysis identified risk factors for MM
      after PD: concomitant CR [odds ratio (OR)-3.19, P < 0.001], smoking (OR-1.92, P =
      0.005), a lack of functional independence (OR-3.29, P = 0.018), cardiac disease
      (OR-2.39, P = 0.011), decreased albumin (per g/dl, OR-1.38, P = 0.033) and a
      longer operative time (versus median time, OR-1.56, P = 0.029). Independent
      predictors of mortality included concomitant CR (OR-3.16, P = 0.010), ventilator
      dependence (OR-13.87, P < 0.001) and septic shock (OR-6.02, P < 0.001).
      CONCLUSIONS: CR was an independent predictor of MM and mortality after a PD.
      Patients requiring PD+CR should be identified pre-operatively, maximally
      optimized and referred to experienced surgeons at expert centres.

PMID- 26223476
TI  - Influence of host nutritional condition on post-infection traits in the
      association between the manipulative acanthocephalan Pomphorhynchus laevis and
      the amphipod Gammarus pulex.
AB  - BACKGROUND: Several parasites with complex life-cycles induce phenotypic
      alterations in their intermediate hosts. According to the host manipulation
      hypothesis, such phenotypic alterations are supposed to increase the fitness of
      the parasite at the expense of that of its intermediate hosts through increasing
      the probability of transmission to next hosts. Although the phenomenon has
      received a large attention, the proximate factors modulating the occurrence and
      intensity of host manipulation remain poorly known. It has however, been
      suggested that the amount of energy reserves in the intermediate host might be a
      key parameter, although its precise influence on the intensity of manipulation
      remains unclear. Dietary depletion in the host may also lead to compromise with
      other parasite traits, such as probability of establishing or growth or
      virulence. METHODS: Here, we address the question through performing experimental
      infections of the freshwater amphipod Gammarus pulex with two different
      populations of the acanthocephalan fish parasite Pomphorhynchus laevis, and
      manipulation of host nutritional condition. Following exposure, gammarids were
      given either a "standard" diet (consisting of elm leaves and chironomid larvae)
      or a "deprived" food treatment (deprived in proteins), and infection parameters
      were recorded. Once parasites reached the stage at which they become infective to
      their definitive host, refuge use (a behavioural trait presumably implied in
      trophic transmission) was assessed, and metabolic rate was measured. RESULTS:
      Infected gammarids exposed to the deprived food treatment showed a lower
      metabolic rate, indicative of a lower body condition, compared to those exposed
      to the standard food treatment. Parasite size was smaller, and, depending on the
      population of origin of the parasites, intensity of infection was lower or
      mortality was higher in deprived hosts. However, food treatment had no effect on
      either the timing or intensity of behavioural modifications. CONCLUSIONS:
      Overall, while our results suggest that acanthocephalan parasites develop better
      in hosts in good condition, no evidence was found for an influence of host
      nutritional condition on host manipulation by parasites.

PMID- 26223478
TI  - Nickel-Catalyzed Cyclopropanation with NMe4OTf and nBuLi.
AB  - Nickel was identified as a catalyst for the cyclopropanation of unactivated
      olefins by using in situ generated lithiomethyl trimethylammonium triflate as a
      methylene donor. A mechanistic hypothesis is proposed in which the generation of
      a reactive nickel carbene explains several interesting observations.
      Additionally, our findings shed light on a report by Franzen and Wittig published
      in 1960 that had been retracted later owing to irreproducibility, and provide a
      rational basis for the systematic development of the reaction for preparative
      purposes as an alternative to diazomethane or Simmons-Smith conditions. 

PMID- 26223477
TI  - Surgical site infection in critically ill patients with secondary and tertiary
      peritonitis: epidemiology, microbiology and influence in outcomes.
AB  - BACKGROUND: Surgical site infection (SSI) remains a significant problem in the
      postoperative period that can negatively affect clinical outcomes. Microbiology
      findings are typically similar to other nosocomial infections, with differences
      dependent on microbiology selection due to antibiotic pressure or the resident
      flora. However, this is poorly understood in the critical care setting. We
      therefore aimed to assess the incidence, epidemiology and microbiology of SSI and
      its association with outcomes in patients with severe peritonitis in the
      intensive care unit (ICU). METHODS: We prospectively studied 305 consecutive
      patients admitted to our surgical ICU from 2010 to 2014 with a diagnosis of
      secondary or tertiary peritonitis. We collected the following data: SSI
      diagnosis, demographics, Acute Physiology and Chronic Health Evaluation (APACHE)
      II score, Simplified Acute Physiology Score (SAPS) II score, type of surgery,
      microbiology, antibiotic treatment and outcomes. Microbiological sampling was
      done by means of swabs. RESULTS: We identified 269 episodes of SSI in 162
      patients (53.1%) aged 64.4 +/- 14.3 years, of which 200 episodes occurred in men
      (64.6%). The mean APACHE II and SAPS II scores were 19.7 +/- 7.8 and 36.5 +/-
      16.1 respectively. The mean ICU and hospital stays were 19.8 +/- 24.8 and 21.7 +/
      30 days respectively. Pseudomonas spp. (n = 52, 19.3%), Escherichia coli (n =
      55, 20.4%) and Candida spp. (n = 46, 17.1%) were the most frequently isolated
      microorganisms, but gram-positive cocci (n = 80, 29.7%) were also frequent.
      Microorganisms isolated from SSIs were associated with a higher incidence of
      antibiotic resistance (64.9%) in ICU patients, but not with higher in-hospital
      mortality. However, patients who suffered from SSI had longer ICU admissions
      (odds ratio = 1.024, 95% confidence interval 1.010-1.039, P = 0.001).
      CONCLUSIONS: The incidence of SSI in secondary or tertiary peritonitis requiring
      ICU admission is very high. Physicians may consider antibiotic-resistant
      pathogens, gram-positive cocci and fungi when choosing empiric antibiotic
      treatment for SSI, although more studies are needed to confirm our results due to
      the inherent limitations of the microbiological sampling with swabs performed in
      our research. The presence of SSI may be associated with prolonged ICU stays, but
      without any influence on overall mortality.

PMID- 26223479
TI  - A New Conformation With an Extraordinarily Long, 3.04 A Two-Electron, Six-Center
      Bond Observed for the pi-[TCNE]2 (2-) Dimer in [NMe4 ]2 [TCNE]2
      (TCNE=Tetracyanoethylene).
AB  - [NMe4 ]2 [TCNE]2 (TCNE=tetracyanoethenide) formed from the reaction of TCNE and
      (NMe4 )CN in MeCN has nuCN IR absorptions at 2195, 2191, 2172, and 2156 cm(-1)
      and a nuCC absorption at 1383 cm(-1) that are characteristic of reduced TCNE. The
      TCNEs have an average central C?C distance of 1.423 A that is also characteristic
      of reduced TCNE. The reduced TCNE forms a previously unknown non-eclipsed,
      centrosymmetric pi-[TCNE]2 (2-) dimer with nominal C2 symmetry, 12 sub van der
      Waals interatomic contacts <3.3 A, a central intradimer separation of 3.039(3) A,
      and comparable intradimer C???N distances of 3.050(3) and 2.984(3) A. The two
      pairs of central C???C atoms form a ?C-C???C-C of 112.6 degrees  that is
      substantially greater than the 0 degrees  observed for the eclipsed D2h pi
      [TCNE]2 (2-) dimer possessing a two-electron, four-center (2e(-) /4c) bond with
      two C???C components from a molecular orbital (MO) analysis. A MO study combining
      CAS(2,2)/MRMP2/cc-pVTZ and atoms-in-molecules (AIM) calculations indicates that
      the non-eclipsed, C2 pi-[TCNE]2 (2-) dimer exhibits a new type of a long,
      intradimer bond involving one strong C???C and two weak C???N components, that
      is, a 2e(-) /6c bond. The C2 pi-[TCNE]2 (2-) conformer has a singlet, diamagnetic
      ground state with a thermally populated triplet excited state with J/kB =1000 K
      (700 cm(-1) ; 86.8 meV; 2.00 kcal mol(-1) ; H=-2 JSa ?Sb ); at the CAS(2,2)/MBMP2
      level the triplet is computed to be 9.0 kcal mol(-1) higher in energy than the
      closed-shell singlet ground state. The results from CAS(2,2)/NEVPT2/cc-pVTZ
      calculations indicate that the C2 and D2h conformers have two different local
      metastable minima with the C2 conformer being 1.3 kcal mol(-1) less stable. The
      different natures of the C2 and D2h conformers are also noted from the results of
      valence bond (VB) qualitative diagram that shows a 10e(-) /6c bond with one C???C
      and two C???N bonding components for the C2 conformer as compared to the 6e(-)
      /4c bond for the D2h conformer with two C???C bonding components.

PMID- 26223480
TI  - Improving geographical knowledge--Links and apps.

PMID- 26223481
TI  - Emission enhancement and polarization of semiconductor quantum dots with
      nanoimprinted plasmonic cavities: towards scalable fabrication of plasmon-exciton
      displays.
AB  - Here we present an application of a high throughput nanofabrication technique to
      the creation of a plasmonic metasurface and demonstrate its application to the
      enhancement and control of radiation by quantum dots (QDs). The metasurface
      consists of an array of cold-forged rectangular nanocavities in a thin silver
      film. High quantum efficiency graded alloy CdSe/CdS/ZnS quantum dots were spread
      over the metasurface and the effects of the plasmon-exciton interactions
      characterised. We found a four-fold increase in the QDs radiative decay rate and
      emission brightness, compared to QDs on glass, along with a degree of linear
      polarisation of 0.73 in the emitted field. Such a surface could be easily
      integrated with current QD display or organic solar cell designs. 

PMID- 26223483
TI  - Bowel Perforation After Treatment with Sorafenib: A Case Report and Review of
      Literature.

PMID- 26223482
TI  - The impact of an inosine triphosphate pyrophosphatase genotype on bilirubin
      increase in chronic hepatitis C patients treated with simeprevir, pegylated
      interferon plus ribavirin.
AB  - BACKGROUND: Hyperbilirubinemia, mild or moderate, is a commonly observed
      laboratory abnormality in chronic hepatitis C patients treated with simeprevir
      with pegylated interferon (Peg-IFN) plus ribavirin. In this prospective,
      multicenter study, we aimed to investigate the clinical features and factors
      associated with bilirubin increases during the therapy. METHODS: A total of 192
      patients with chronic hepatitis C who were treated with simeprevir with Peg-IFN
      plus ribavirin were analyzed. RESULTS: The mean serum bilirubin level increased
      significantly during the initial 12 weeks of simeprevir administration and peaked
      at 2 weeks after the administration. Hyperbilirubinemia of more than 2 mg/dl
      developed in 18% of the patients; in 85% of those patients, the bilirubin levels
      peaked within 6 weeks and gradually decreased thereafter. A univariable analysis
      revealed that an increase in serum total bilirubin of 1.0 mg/dl or more from
      baseline was significantly associated with the sex, red blood cell count, serum
      hemoglobin level, serum alanine aminotransferase level, serum creatinine level
      and inosine triphosphate pyrophosphatase (ITPA) genotype. In the multivariable
      analysis, the ITPA genotype (CC odds ratio 4.990, p = 0.011) was found to be the
      only independent factor. Consistent with this result, there was a significant
      correlation between hyperbilirubinemia and the degree of hemolytic anemia.
      CONCLUSIONS: Hyperbilirubinemia develops at early time points after simeprevir
      administration in most cases and is dependent on the ITPA genotype. Careful
      attention should be paid to hyperbilirubinemia, which occurs at later time points
      or in patients with an ITPA non-CC genotype so that a diagnosis of liver damage
      with hyperbilirubinemia is not missed.

PMID- 26223484
TI  - CPAP therapy induces favorable short-term changes in epicardial fat thickness and
      vascular and metabolic markers in apparently healthy subjects with obstructive
      sleep apnea-hypopnea syndrome (OSAHS).
AB  - BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent
      risk factor for hypertension, coronary artery disease, and diabetes mellitus.
      Epicardial fat has been recently recognized as a new risk factor and active
      participant on cardiometabolic risk. The aim of this study was to assess an
      independent relationship between sleep apnea severity, metabolic and vascular
      markers, and epicardial fat, at baseline and after 3 months of continuous
      positive airway pressure (CPAP) therapy. MATERIALS AND METHOD: Our study group
      consisted of 48 patients with suspected OSAHS and no prior history of
      cardiovascular disease or diabetes mellitus. All patients underwent full
      overnight polysomnography. Thickness of epicardial and visceral adipose tissue,
      brachial artery flow-mediated dilation (FMD), carotid intima media thickness
      (cIMT), pulse wave velocity (PWV), plasma C-reactive protein (CRP) levels,
      fasting glucose levels, HbA1c, homeostatic model assessment of insulin resistance
      index (HOMA), and lipid profile were measured at baseline and after 3 months of
      CPAP use in patients with moderate to severe OSAHS. RESULTS: In OSAHS patients
      (Apnea-hypopnea index (AHI) >=15/h, N = 28), epicardial fat correlated with
      fasting glucose (rho = 0.406, p = 0.04) and HOMA (rho = 0.525, p = 0.049) but was
      not associated with visceral fat (rho = 0.126, p = 0.595). Epicardial adipose
      tissue (EAT) (p = 0.022) increased across AHI severity along with PWV (p = 0.045)
      and carotid intima media thickness (IMT) (p = 0.034) while FMD (p = 0.017)
      decreased. Therapy with CPAP reduced both epicardial (p < 0.001) and visceral fat
      (p = 0.001). Alterations in epicardial fat across the follow-up were associated
      with changes in PWV (p = 0.026) and HOMA (p = 0.037) independently of major
      confounders. CONCLUSIONS: Epicardial fat thickness was associated with OSA
      severity and may be an additional marker of cardiovascular risk as well as of
      future diabetes in these patients. CPAP therapy reduced epicardial fat,
      suggesting its potentially beneficial role in reducing cardiometabolic risk in
      OSA patients.

PMID- 26223486
TI  - Sentinel lymph node assessment in breast cancer patients receiving neo-adjuvant
      chemotherapy: to biopsy before or after?

PMID- 26223485
TI  - Patients' Expectations Predict Surgery Outcomes: A Meta-Analysis.
AB  - BACKGROUND: Several studies indicate that patients' presurgical expectations can
      influence postsurgical health outcome. PURPOSE: To estimate the potential for
      clinical exploitation of this association, a meta-analysis of prospective studies
      which assess the association between patients' presurgical expectations and
      postsurgical quality of life is applied to accumulate the overall effect.
      METHODS: We searched the databases MEDLINE, CENTRAL, and PsychINFO for English-
      and German-language articles published from 1980 until December 2013.
      Additionally, manual searches of bibliographies of retrieved articles and
      relevant reviews were conducted. Prospective studies measuring presurgical
      expectations and postsurgical quality of life in patients aging 18-65 were
      selected. Correlations between presurgical expectations and postsurgical quality
      of life were extracted or provided by the authors. RESULTS: The search yielded 21
      prospective studies (including 2611 patients undergoing surgery) with a follow-up
      period ranging from 1 week to 13 years. The pooled correlations were 0.369 (95%
      confidence interval (CI), 0.264 to 0.466; P for heterogeneity <0.001; random
      effects model) for overall quality of life (11 studies), 0.126 (95% CI, 0.079 to
      0.172; P for heterogeneity = 0.63; random-effects model) for physical quality of
      life (12 studies), and 0.208 (95% CI, 0.113 to 0.299; P for heterogeneity <0.001;
      random-effects model) for mental quality of life (12 studies), indicating low to
      moderate associations between presurgery patients' expectations and postsurgery
      quality of life. CONCLUSIONS: These results confirm the importance of patients'
      expectations in the prediction of postsurgical outcomes and underline the
      necessity to optimize these expectations in order to improve postoperative
      quality of life.

PMID- 26223488
TI  - Treatment of odor by a seashell biofilter at a wastewater treatment plant.
AB  - Biofilters are becoming an increasingly popular treatment device for odors and
      other volatiles found at wastewater treatment plants. A seashell media based
      biofilter was installed in April 2011 at Lake Wildwood Wastewater Treatment Plant
      located in Penn Valley, California. It was sampled seasonally to examine its
      ability to treat odorous compounds found in the air above the anaerobic
      equalization basin at the front end of the plant and to examine the properties of
      the biofilter and its recirculating water system. The odor profile method sensory
      panels found mainly sulfide odors (rotten eggs and rotten vegetable) and some
      fecal odors. This proved to be a useful guidance tool for selecting the required
      types of chemical sampling. The predominant odorous compounds found were hydrogen
      sulfide, methyl mercaptan and dimethyl sulfide. These compounds were effectively
      removed by the biofilter at greater than 99% removal efficiency therein reducing
      the chemical concentrations to below their odor thresholds. Aldehydes found in
      the biofilter were below odor thresholds but served as indicators of biological
      activity. Gas chromatography with mass spectrometry and gas chromatography with
      sensory detection showed the presence of dimethyl disulfide and dimethyl
      trisulfide as well, but barely above their respective odor thresholds. The
      neutrality of the pH of the recirculating water was variable depending on
      conditions in the biofilter, but a local neutral pH was found in the shells
      themselves. Other measurements of the recirculating water indicated that the
      majority of the bio-activity takes place in the first stage of the biofilter. All
      measurements performed suggest that this seashell biofilter is successful at
      removing odors found at Lake Wildwood. This study is an initial examination into
      the mechanism of the removal of odorous compounds in a seashell biofilter.
      IMPLICATIONS: This paper presents a thorough examination of a seashell media
      biofilter, a sustainable treatment technology used to remove reduced sulfide
      compounds. The durable performance of the seashell biofilter ensures that odors
      will be adequately controlled, preventing odor nuisance to surrounding
      residences, which is an emerging problem faced by waste management facilities.
      The odor profile method technique used in this study can be applied in many
      situations by waste management facilities and regulatory air management
      organizations for source tracking in relation to prevention and management of
      odor complaints, respectively.

PMID- 26223487
TI  - Regulated expression of murine CD40L by a lentiviral vector transcriptionally
      targeted through its endogenous promoter.
AB  - BACKGROUND: Targeted lentiviral vectors may contribute to circumventing
      genotoxicity associated with uncontrolled transcription of therapeutic genes.
      Some vectors replacing strong viral sequences for gene promoters such as beta
      globin, CD4, CD19 or Igkappa were able to drive tissue-specific expression of the
      transgene. Gene therapy, however, faces even greater hurdles when the therapeutic
      transgene is subject to strict regulatory mechanisms. This is the case of the
      CD40LG gene, which encodes for the CD154 (also known as CD40L) molecule,
      transiently expressed upon activation on CD4(+) T cells. Mutations in this gene
      cause the X-linked hyper IgM syndrome (HIGM1) in humans because the interaction
      of CD40L with its ligand CD40 triggers signals that are critical for the
      immunobiology of B lymphocytes. METHODS: We developed a lentiviral vector
      containing the murine Cd40lg cDNA under the control of its endogenous promoter.
      RESULTS: The CD4(+) BW5147 T cells transduced with the pCd40lg-Cd40lg lentiviral
      vector express CD40L only upon stimulation. The intensity of the expression
      correlates with the number of vector integrations per cell and detected molecules
      rapidly decay after removing the stimulating agent. The tissue-specific,
      activation-dependent and reversible expression of CD40L fully mimics the
      physiological induction and disappearance of the molecule from the surface of
      murine T lymphocytes. The functional activity of the regulated lentiviral vector
      is demonstrated by the ability of transduced BW5147 cells to promote the
      proliferation of purified B cell splenocytes. CONCLUSIONS: We have developed a
      fine-regulated lentiviral vector that can be a model for expressing molecules
      subject to stringent regulatory mechanisms.

PMID- 26223489
TI  - Array-based sensing of purine derivatives with fluorescent dyes.
AB  - Natural and synthetic purine derivatives such as caffeine, theophylline, 6
      mercaptopurine and 8-chlorotheophylline are important drugs. Due to the
      structural similarity of these compounds, it is intrinsically difficult to
      prepare chemosensors for their selective optical detection. Here, we describe a
      sensor array which can be used to differentiate pharmacologically important
      purine derivatives with good accuracy. The array is composed of four
      polysufonated fluorescent dyes, all of which can bind purines viapi-stacking
      interactions. The complexation of the analytes results in partial quenching of
      the fluorescence. The fluorescence response of the four dyes provides a
      characteristic signal pattern, enabling the identification of thirteen purine
      derivatives at low millimolar concentration. Furthermore, it is possible to use
      the array for obtaining information about the quantity and purity of purine
      samples. 

PMID- 26223490
TI  - Appropriate therapy for type 2 diabetes mellitus in view of pancreatic beta-cell
      glucose toxicity: "the earlier, the better".
AB  - Pancreatic beta-cells secrete insulin when blood glucose levels become high;
      however, when beta-cells are chronically exposed to hyperglycemia, beta-cell
      function gradually deteriorates, which is known as beta-cell glucose toxicity. In
      the diabetic state, nuclear expression of the pancreatic transcription factors
      pancreatic and duodenal homeobox 1 (PDX-1) and v-Maf musculoaponeurotic
      fibrosarcoma oncogene family, protein A (MafA) is decreased. In addition,
      incretin receptor expression in beta-cells is decreased, which is likely involved
      in the impairment of incretin effects in diabetes. Clinically, it is important to
      select appropriate therapy for type 2 diabetes mellitus (T2DM) so that beta-cell
      function can be preserved. In addition, when appropriate pharmacological
      interventions against beta-cell glucose toxicity are started at the early stages
      of diabetes, beta-cell function is substantially restored, which is not observed
      if treatment is started at advanced stages. These observations indicate that it
      is likely that downregulation of pancreatic transcription factors and/or incretin
      receptors is involved in beta-cell dysfunction observed in T2DM and it is very
      important to start appropriate pharmacological intervention against beta-cell
      glucose toxicity in the early stages of diabetes. 

PMID- 26223491
TI  - The role of dynamically induced variability in the recent warming trend slowdown
      over the Northern Hemisphere.
AB  - Since the slowing of the trend of increasing surface air temperature (SAT) in the
      late 1990 s, intense interest and debate have arisen concerning the contribution
      of human activities to the warming observed in previous decades. Although several
      explanations have been proposed for the warming-trend slowdown (WTS), none has
      been generally accepted. We investigate the WTS using a recently developed
      methodology that can successfully identify and separate the dynamically induced
      and radiatively forced SAT changes from raw SAT data. The dynamically induced SAT
      changes exhibited an obvious cooling effect relative to the warming effect of the
      adjusted SAT in the hiatus process. A correlation analysis suggests that the
      changes are dominated primarily by the North Atlantic Oscillation (NAO), Pacific
      Decadal Oscillation (PDO), and Atlantic Multidecadal Oscillation (AMO). Our
      results confirm that dynamically induced variability caused the WTS. The
      radiatively forced SAT changes are determined mainly by anthropogenic forcing,
      indicating the warming influence of greenhouse gases (GHGs), which reached levels
      of 400 ppm during the hiatus period. Therefore, the global SAT will not remain
      permanently neutral. The increased radiatively forced SAT will be amplified by
      increased dynamically induced SAT when the natural mode returns to a warming
      phase in the next period.

PMID- 26223492
TI  - Dosimetric evaluation of anatomical changes during treatment to identify criteria
      for adaptive radiotherapy in oesophageal cancer patients.
AB  - BACKGROUND: Some oesophageal cancer patients undergoing chemotherapy and
      concomitant radiotherapy (chemoRT) show large interfractional anatomical changes
      during treatment. These changes may modify the dose delivered to the target and
      organs at risk (OARs). The aim of the presenwt study was to investigate the
      dosimetric consequences of anatomical changes during treatment to obtain criteria
      for an adaptive RT decision support system. MATERIAL AND METHODS: Twenty-nine
      patients were treated with chemoRT for oesophageal and gastro-oesophageal
      junction cancer and set up according to daily cone beam computed tomography
      (CBCTs) scans. All patients had an additional replanning CT scan at median
      fraction number 10 (9-14), which was deformably registered to the original
      planning CT. Gross tumour volumes (GTVs), clinical target volumes (CTVs) and OARs
      were transferred to the additional CT and corrected by an exwperienced physician.
      Treatment plans were recalculated and dose to targets and OARs was evaluated.
      Treatment was adapted if the volume receiving 95% of the prescribed dose (V95%)
      coverage of CTV decreased > 1% or planning target volume (PTV) decreased by > 3%.
      RESULTS: In total, nine adaptive events were observed: All nine were triggered by
      PTV V95% decrease > 3% [median 11% (5-41%)] and six of these were additionally
      triggered by CTV V95% decrease > 1% [median 5% (2-35%)]. The largest
      discrepancies were caused by interfractional baseline or amplitude shifts in
      diaphragm position (n = 5). Mediastinal (n = 6), oesophageal (n = 6) and bowel
      filling changes (n = 2) caused the remainder of the changes. For patients with
      dosimetric changes exceeding the adaptation limits, the discrepancies were
      confirmed by inspecting the daily CBCTs. In 31% of all patients, heart V30Gy
      increased more than 2% (maximum 5%). Only minor changes in lung dose or liver
      dose were seen. CONCLUSION: Target coverage throughout the course of chemoRT
      treatment is compromised in some patients due to interfractional anatomical
      changes. Dose to the heart may increase as well.

PMID- 26223493
TI  - Modulatory effects of ketamine, risperidone and lamotrigine on resting brain
      perfusion in healthy human subjects.
AB  - RATIONALE: Resting brain perfusion, measured using the MRI-based arterial spin
      labelling (ASL) technique, is sensitive to detect central effects of single,
      clinically effective, doses of pharmacological compounds. However,
      pharmacological interaction experiments, such as the modulation of one drug
      response in the presence of another, have not been widely investigated using a
      task-free ASL approach. OBJECTIVES: We assessed the effects of three psychoactive
      compounds (ketamine, risperidone and lamotrigine), and their interaction, on
      resting brain perfusion in healthy human volunteers. METHODS: A multivariate
      Gaussian process classification (GPC) and more conventional univariate analyses
      were applied. The four pre-infusion conditions for each subject comprised
      risperidone, lamotrigine and two placebo sessions. The two placebo conditions
      enabled us to evaluate the classification performance in a test-retest setting,
      in addition to its performance in distinguishing the active oral drugs from
      placebo (direct effect on brain perfusion). The post ketamine- or saline-infusion
      scans allowed the effect of ketamine, and its interaction with risperidone and
      lamotrigine, on brain perfusion to be characterised. RESULTS: The pseudo
      continuous ASL measurements of perfusion were sensitive to the effects of
      ketamine infusion and risperidone. The GPC captured consistent changes in
      perfusion across the group and contextualised the univariate changes with a
      larger pattern of regions contributing to accurate discrimination of ketamine
      from placebo. CONCLUSIONS: The findings argue against perfusion changes
      confounding in the previously described evoked BOLD response to ketamine and
      emphasise the blockade of the NMDA receptor over neuronal glutamate release in
      determining the perfusion changes induced by ketamine.

PMID- 26223495
TI  - Knotless technique for iridodialysis repair.

PMID- 26223494
TI  - Cortical GluN2B deletion attenuates punished suppression of food reward-seeking.
AB  - RATIONALE: Compulsive behavior, which is a hallmark of psychiatric disorders such
      as addiction and obsessive-compulsive disorder, engages corticostriatal circuits.
      Previous studies indicate a role for corticostriatal N-methyl-D-aspartate
      receptors (NMDARs) in mediating compulsive-like responding for drugs of abuse,
      but the specific receptor subunits controlling reward-seeking in the face of
      punishment remain unclear. OBJECTIVES: The current study assessed the involvement
      of corticostriatal GluN2B-containing NMDARs in measures of persistent and
      punished food reward-seeking. METHODS: Mice with genetic deletion of GluN2B in
      one of three distinct neuronal populations, cortical principal neurons, forebrain
      interneurons, or striatal medium spiny neurons, were tested for (1) sustained
      food reward-seeking when reward was absent, (2) reward-seeking under a
      progressive ratio schedule of reinforcement, and (3) persistent reward-seeking
      after a footshock punishment. RESULTS: Mutant mice with genetic deletion of
      GluN2B in cortical principal neurons demonstrated attenuated suppression of
      reward-seeking during punishment. These mice performed normally on other
      behavioral measures, including an assay for pain sensitivity. Mutants with
      interneuronal or striatal GluN2B deletions were normal on all behavioral assays.
      CONCLUSIONS: Current findings offer novel evidence that loss of GluN2B-containing
      NMDARs expressed on principal neurons in the cortex results in reduced punished
      food reward-seeking. These data support the involvement of GluN2B subunit in
      cortical circuits regulating cognitive flexibility in a variety of settings, with
      implications for understanding the basis of inflexible behavior in
      neuropsychiatric disorders including obsessive-compulsive disorders (OCD) and
      addictions.

PMID- 26223497
TI  - Value of a facilitated quality improvement initiative on cardiovascular disease
      risk: findings from an evaluation of the Aggressively Treating Global
      Cardiometabolic Risk Factors to Reduce Cardiovascular Events (AT GOAL).
AB  - RATIONALE, AIMS AND OBJECTIVES: In the United States, cardiovascular disease
      (CVD) is the leading cause of death. The US Centers for Disease Control and
      Prevention contracted an evaluation of the Aggressively Treating Global
      Cardiometabolic Risk Factors to Reduce Cardiovascular Events (AT GOAL) programme
      as part of its effort to identify strategies to address CVD risk factors.
      METHODS: This study analysed patient-level data from 7527 patients in 43 primary
      care practices. The researchers assessed average change in control rates for CVD
      related measures across practices, and then across patients between baseline and
      a patient's last visit during the practice's tenure in the programme (referred to
      as 'end line') using repeated measures analysis of variance and random effects
      generalized least squares, respectively. RESULTS: Among non-diabetic patients,
      there were significant increases in control rates for overall blood pressure
      (74.3% to 78.0%, P = 0.0002), systolic blood pressure (70.3% to 80.6%, P =
      0.0099), diastolic blood pressure (90.1% to 92.7%, P = 0.0001) and low-density
      lipoprotein (LDL; 48.6% to 53.1%, P = 0.0001) between baseline and end line.
      Among diabetic patients, there was a significant increase in diastolic blood
      pressure control (59.8% to 61.9%, P = 0.0141). While continuous CVD-related
      outcomes show an overall trend between baseline and end line, patients with
      uncontrolled measures at baseline showed a decrease between baseline and end line
      relative to their counterparts who were controlled at baseline. CONCLUSIONS:
      Findings from the AT GOAL evaluation support the value of a facilitated quality
      improvement (QI) initiative on managing CVD risk.

PMID- 26223499
TI  - Mutational profile of childhood myeloproliferative neoplasms.

PMID- 26223500
TI  - Genetic deletion of monoacylglycerol lipase leads to impaired cannabinoid
      receptor CB1R signaling and anxiety-like behavior.
AB  - Endocannabinoids (eCB) are key regulators of excitatory/inhibitory
      neurotransmission at cannabinoid-1-receptor (CB1 R)-expressing axon terminals.
      The most abundant eCB in the brain, that is 2-arachidonoylglycerol (2-AG), is
      hydrolyzed by the enzyme monoacylglycerol lipase (MAGL), whose chronic inhibition
      in the brain was reported to cause CB1 R desensitization. We employed the MAGL
      knock-out mouse (MAGL-/-), a genetic model of congenital and sustained elevation
      of 2-AG levels in the brain, to provide morphological and biochemical evidence
      for beta-arrestin2-mediated CB1 R desensitization in brain regions involved in
      the control of emotional states, that is, the prefrontal cortex (PFC), amygdala,
      hippocampus and cerebellar cortex. We found a widespread CB1 R/beta-arrestin2 co
      expression in the mPFC, amygdala and hippocampus accompanied by impairment of
      extracellular signal-regulated kinase signaling and elevation of vesicular
      glutamate transporter (VGluT1) at CB1 R-positive excitatory terminals in the
      mPFC, or vesicular GABA transporter (VGAT) at CB1 R-positive inhibitory terminals
      in the amygdala and hippocampus. The impairment of CB1 R signaling in MAGL-/-
      mice was also accompanied by enhanced excitatory drive in the basolateral
      amygdala (BLA)-mPFC circuit, with subsequent elevation of glutamate release to
      the mPFC and anxiety-like and obsessive-compulsive behaviors, as assessed by the
      light/dark box and marble burying tests, respectively. Collectively, these data
      provide evidence for a beta-arrestin2-mediated desensitization of CB1 R in MAGL-/
      mice, with impact on the synaptic plasticity of brain circuits involved in
      emotional functions. In this study, the authors provide evidence that
      congenitally enhanced endocannabinoid levels in the neuronal circuits underlying
      anxiety-like behavioral states (mainly medial prefrontal cortex, amygdala and
      hippocampus) lead to CB1R desenistization and anxiety and depression. MAGL-/-
      mice, a model of congenital overactivity of the eCB system, exhibited a
      compensatory impairment of CB1R signaling in anxiety-associated brain areas and a
      subsequent change in excitatory/inhibitory tone associated with altered score in
      the marble burying and light/dark box test, in concomitance with anxiety and
      depression behavior states. These findings may have potential relevance to the
      understanding of the neurochemical effects of chronic CB1R overstimulation in
      cannabis abusers.

PMID- 26223502
TI  - Nasseem Husain: homage to a pioneer of cytology automation.
AB  - Dr Oliver Anthony Nasseem Husain, who died on 22 September 2014, aged 90 years,
      was one of the great names of European cytology, a pioneer of automated cervical
      screening and a founding member of both the British Society for Clinical Cytology
      (BSCC) and the European Federation of Cytology Societies (EFCS). The life of this
      one remarkable man involved much of the pioneering work, which is reviewed in
      this article, that has brought conventional cytology to the complex multimodal
      discipline it is today. 

PMID- 26223503
TI  - Dynamic multi-coil tailored excitation for transmit B1 correction at 7 Tesla.
AB  - PURPOSE: Tailored excitation (TEx) based on interspersing multiple radio
      frequency pulses with linear gradient and higher-order shim pulses can be used to
      obtain uniform flip angle in the presence of large radio frequency transmission
      (B 1+) inhomogeneity. Here, an implementation of dynamic, multislice tailored
      excitation using the recently developed multi-coil nonlinear shim hardware (MC
      DTEx) is reported. METHODS: MC-DTEx was developed and tested both in a phantom
      and in vivo at 7 T, and its efficacy was quantitatively assessed. Predicted
      outcomes of MC-DTEx and DTEx based on spherical harmonic shims (SH-DTEx) were
      also compared. RESULTS: For a planned 30  degrees  flip angle, in a phantom, the
      standard deviation in excitation improved from 28% (regular excitation) to 12%
      with MC-DTEx. The SD in in vivo excitation improved from 22 to 12%. The
      improvements achieved with experimental MC-DTEx closely matched the theoretical
      predictions. Simulations further showed that MC-DTEx outperforms SH-DTEx for both
      scenarios. CONCLUSION: Successful implementation of multislice MC-DTEx is
      presented and is shown to be capable of homogenizing excitation over more than
      twofold B 1+ variations. Its benefits over SH-DTEx are also demonstrated. A
      distinct advantage of MC hardware over SH shim hardware is the absence of
      significant eddy current effects, which allows for a straightforward, multislice
      implementation of MC-DTEx. Magn Reson Med 76:83-93, 2016. (c) 2015 Wiley
      Periodicals, Inc.

PMID- 26223504
TI  - Gene expression profiling offers insights into the role of innate immune
      signaling in SSc.
AB  - Systemic sclerosis (SSc) is characterized by inflammation, vascular dysfunction,
      and ultimately fibrosis. Progress in understanding disease pathogenesis and
      developing effective disease treatments has been hampered by an incomplete
      understanding of SSc heterogeneity. To clarify this, we have used genomic
      approaches to identify distinct patient subsets based on gene expression patterns
      in SSc skin and other end-target organs. Here, we review what is known about the
      gene expression-based subsets in SSc, currently defined as the inflammatory,
      fibroproliferative, limited, and normal-like subsets. The inflammatory subset of
      patients is characterized by infiltrating immune cells that include T cells,
      macrophages, and possibly dendritic cells, although little is known about the
      mediators these cells secrete and the pathways that govern cell activation. Prior
      studies have suggested a role for pathogens as a trigger of immune responses in
      SSc, and recent data have identified viral and mycobiome components as potential
      environmental triggers. We present a model based on analyses of gene expression
      data and a review of the literature, which suggests that the gene expression
      subsets observed in patients possibly represent distinct, interconnected
      molecular states of disease, to which an innate immune response is central that
      results in the generation of clinical disease. 

PMID- 26223506
TI  - Quantitative comparison of topical aluminum salt solution efficacy for management
      of sweating: a randomized, controlled trial.
AB  - BACKGROUND: There is a lack of studies objectively comparing the efficacy of
      topical antiperspirants in reducing sweat. OBJECTIVE: To objectively and
      quantitatively compare the efficacy of two aluminum salt solutions for the
      reduction of induced sweating. METHODS: A subject, rater, and statistician
      blinded, randomized, controlled trial. Nineteen subjects were exposed to a
      standardized heat challenge for 3 h. Topical agent A (20% aluminum chloride
      hexahydrate) was randomized to either axilla, and topical agent B (1% aluminum
      acetate) assigned to the contralateral side. A sauna suit induced sweating during
      three 30-min heat intervals: (1) with no study agents (pre); (2) with both study
      agents, one on each side; and (3) after the agents were washed off (post). Sweat
      levels were measured by securing Whatman((r)) filter paper to each axilla and
      measuring the paper weight after each heat interval. The difference in paper
      weight following each heat interval between Study Agent A and Study Agent B was
      measured by a gravimetric scale. RESULTS: Topical agent A had a significantly
      greater effect at reducing axillary sweating than B (P = 0.0002). CONCLUSION: In
      a sweating simulation, 20% aluminum chloride hexahydrate quantitatively and
      objectively appeared to reduce sweat more effectively than 1% aluminum acetate.

PMID- 26223507
TI  - Chlorhexidine markedly potentiates the oxidants scavenging abilities of Candida
      albicans.
AB  - The oxidant scavenging ability (OSA) of catalase-rich Candida albicans is
      markedly enhanced by chlorhexidine digluconate (CHX), polymyxin B, the bile salt
      ursodeoxycholate and by lysophosphatidylcholine, which all act as detergents
      facilitating the penetration of oxidants and their intracellular decomposition.
      Quantifications of the OSA of Candida albicans were measured by a highly
      sensitive luminol-dependent chemiluminescence assay and by the Thurman's assay,
      to quantify hydrogen peroxide (H2O2). The OSA enhancing activity by CHX depends
      to some extent on the media on which candida grew. The OSA of candida treated by
      CHX was modulated by whole human saliva, red blood cells, lysozyme, cationic
      peptides and by polyphenols. Concentrations of CHX, which killed over 95 % of
      Candida albicans cells, did not affect the cells' abilities to scavenge reactive
      oxygen species (ROS). The OSA of Candida cells treated by CHX is highly
      refractory to H2O2 (50 mM) but is strongly inhibited by hypochlorous acid,
      lecithin, trypan blue and by heparin. We speculate that similarly to catalase
      rich red blood cells, Candida albicans and additional catalase-rich microbiota
      may also have the ability to scavenge oxidants and thus can protect catalase
      negative anaerobes and facultative anaerobes cariogenic streptococci against
      peroxide and thus secure their survival in the oral cavity.

PMID- 26223508
TI  - First trimester ultrasound screening for Down syndrome based on maternal age,
      fetal nuchal translucency and different combinations of the additional markers
      nasal bone, tricuspid and ductus venosus flow.
AB  - OBJECTIVE: To examine the performance of screening for Down syndrome based on
      maternal age, fetal nuchal translucency (NT) and different combinations of the
      additional ultrasound parameters: nasal bone (NB), tricuspid flow (TF) and ductus
      venosus (DV). METHODS: Retrospective study at the University of Tuebingen,
      Germany including women who underwent chorionic villous sampling between 2008 and
      2014. Prior to invasive testing, the crown rump length, NT, NB, TF and DV were
      measured. In each case, the added value of the additional markers NB, TF and DV
      were compared with screening for trisomy 21 based on maternal age (MA) and NT
      thickness alone. RESULTS: A total of 1916 pregnancies met the inclusion criteria,
      including 1823 fetuses with a normal karyotype and 93 with trisomy 21. Screening
      based on MA, fetal NT and one, two and three of the additional ultrasound markers
      resulted in a detection rate of about 80%, 87% and 94%, respectively for a false
      positive rate of 3%. CONCLUSION: Detection rates for trisomy 21 in first
      trimester ultrasound screening are substantially higher if all three additional
      markers rather than just one are assessed.

PMID- 26223505
TI  - Control of autoimmune CNS inflammation by astrocytes.
AB  - Multiple sclerosis is a neurologic disease caused by immune cell infiltration
      into the central nervous system, resulting in gray and white matter inflammation,
      progressive demyelination, and neuronal loss. Astrocytes, the most abundant cell
      population in the central nervous system (CNS), have been considered inert
      scaffold or housekeeping cells for many years. However, recently, it has become
      clear that this cell population actively modulates the immune response in the CNS
      at multiple levels. While being exposed to a plethora of cytokines during ongoing
      autoimmune inflammation, astrocytes modulate local CNS inflammation by secreting
      cytokines and chemokines, among other factors. This review article gives an
      overview of the most recent understanding about cytokine networks operational in
      astrocytes during autoimmune neuroinflammation and highlights potential targets
      for immunomodulatory therapies for multiple sclerosis. 

PMID- 26223498
TI  - The UK-PBC risk scores: Derivation and validation of a scoring system for long
      term prediction of end-stage liver disease in primary biliary cholangitis.
AB  - The biochemical response to ursodeoxycholic acid (UDCA)--so-called "treatment
      response"--strongly predicts long-term outcome in primary biliary cholangitis
      (PBC). Several long-term prognostic models based solely on the treatment response
      have been developed that are widely used to risk stratify PBC patients and guide
      their management. However, they do not take other prognostic variables into
      account, such as the stage of the liver disease. We sought to improve existing
      long-term prognostic models of PBC using data from the UK-PBC Research Cohort. We
      performed Cox's proportional hazards regression analysis of diverse explanatory
      variables in a derivation cohort of 1,916 UDCA-treated participants. We used
      nonautomatic backward selection to derive the best-fitting Cox model, from which
      we derived a multivariable fractional polynomial model. We combined linear
      predictors and baseline survivor functions in equations to score the risk of a
      liver transplant or liver-related death occurring within 5, 10, or 15 years. We
      validated these risk scores in an independent cohort of 1,249 UDCA-treated
      participants. The best-fitting model consisted of the baseline albumin and
      platelet count, as well as the bilirubin, transaminases, and alkaline
      phosphatase, after 12 months of UDCA. In the validation cohort, the 5-, 10-, and
      15-year risk scores were highly accurate (areas under the curve: >0.90).
      CONCLUSIONS: The prognosis of PBC patients can be accurately evaluated using the
      UK-PBC risk scores. They may be used to identify high-risk patients for closer
      monitoring and second-line therapies, as well as low-risk patients who could
      potentially be followed up in primary care.

PMID- 26223509
TI  - Levels of Toxocara infections in dogs and cats from urban Vietnam together with
      associated risk factors for transmission.
AB  - The aims of the present study were to assess the prevalence of Toxocara infection
      in household cats and dogs, together with the presence of anti-Toxocara IgG
      antibodies in humans and the level of egg contamination in soil and vegetable
      samples from the local environment. Prevalence values of 47.8% of 253 cats and
      37.7% of 284 dogs were recorded, together with 35.8% of eggs in soil samples,
      25.0% in garden vegetables and in 56.3% of 16 dog-hair samples. The risk of the
      infection was higher for dogs and cats in households with egg-contaminated soil
      compared to those without evidence of soil contamination. The high prevalence of
      dog and cat Toxocara infection and their indiscriminate defecation behaviour
      contribute to a significant risk of transmission to humans as 58.7% of human
      blood samples were seropositive for Toxocara. Anthelmintic treatment of dogs and
      cats, plus educating household members, must be emphasized in any prevention
      programme in Vietnam. 

PMID- 26223510
TI  - Retinal detachment in hemolysis, elevated liver enzymes, and low platelet count
      (HELLP) syndrome: Color vision abnormality as the first and predominant
      manifestation.
AB  - Serous retinal detachment is sometimes caused by hypertensive disorders in
      pregnancy and its associated conditions, in which the predominant eye symptoms
      are blurred vision, distorted vision, and reduced visual acuity. To our best
      knowledge, this is the first report of a puerperal woman with hemolysis, elevated
      liver enzymes, and low platelet count (HELLP) syndrome in whom color vision
      abnormality was the first and predominant manifestation of serous retinal
      detachment. At 32 weeks of gestation, the 34-year-old Japanese woman underwent
      cesarean section due to HELLP syndrome. She complained of color vision
      abnormality on day 1 post-partum and ophthalmological examination revealed serous
      retinal detachment of both eyes. The visual acuity was preserved. With supportive
      therapy, her color vision abnormality gradually ameliorated and retinal
      detachment completely resolved on day 34 post-partum without any sequelae.
      Obstetricians should be aware that color vision abnormality can be the first and
      predominant symptom of HELLP-related serous retinal detachment. 

PMID- 26223511
TI  - Feasibility and Participant Experiences of a Written Emotional Disclosure
      Intervention for Parental Caregivers of People with Psychosis.
AB  - Caregivers are at increased risk of poor health but often cannot engage with
      health care because of practical constraints. Writing therapies such as written
      emotional disclosure (WED) might represent an accessible therapy for this
      population. This study aimed to determine whether WED is a suitable therapy for
      caregivers of people with psychosis. Data were collected from a feasibility trial
      comparing WED with a neutral writing task. Twenty four participants completed
      writing tasks; the content was analysed using the Linguistic Inquiry Word Count
      (LIWC) programme. Twenty one participants provided feedback about the writing
      task, and data were analysed using Burnard's thematic content analysis. WED was
      feasible to implement in caregivers of people with psychosis. All participants
      ascribed benefit to writing tasks, the majority describing a cathartic effect,
      enjoying time to oneself or distraction from caregiving. Quantitative comparison
      indicated differences in emotional content between intervention and control
      writing. However, qualitative analysis showed that control participants found it
      challenging to write neutrally, the majority citing the care-recipient in their
      writing. Community-based WED is a feasible therapy for caregivers of people with
      psychosis. The need for refinement of the control writing task for use in
      caregivers is discussed. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26223514
TI  - Properly reading the histone code by MS-based proteomics.
AB  - Histone proteins are essential elements for DNA packaging. Their PTMs contribute
      in modeling chromatin structure and recruiting enzymes involved in gene
      regulation, DNA repair, and chromosome condensation. This fundamental aspect,
      together with the fact that histone PTMs can be epigenetically inherited through
      cell generations, enlightens their importance in chromatin biology, and the
      consequent necessity of having biochemical techniques for their characterization.
      Nanoflow LC coupled to MS (nanoLC-MS) is the strategy of choice for protein PTM
      accurate quantification. However, histones require adjustments to the digestion
      protocol such as lysine derivatization to obtain suitable peptides for the
      analysis. nanoLC-MS has numerous advantages, spanning from high confidence
      identification to possibility of high throughput analyses, but the peculiarity of
      the histone preparation protocol requires continuous monitoring with the most
      modern available technologies to question its reliability. The work of Meert et
      al. (Proteomics 2015, 15, 2966-2971) establishes which protocols lead to either
      incomplete derivatization or derivatization of undesired amino acid residues
      using a combination of high resolution MS and bioinformatics tools for the
      alignment and the characterization of nanoLC-MS runs. As well, they identify a
      number of side reactions that could be potentially misinterpreted as biological
      PTMs. 

PMID- 26223513
TI  - Tuning the structures based on polyoxometalates from 1-D to 2-D by using
      different secondary organic ligands.
AB  - Six new organic-inorganic hybrid compounds based on [XM12O40](4-) (X =
      heteroatom, M = metal atom), namely [Cu(pic)2][H2XM12O40].2Hapy.2apy (X = Si, M =
      W for , X = Ge, M = W for and X = Si, M = Mo for ), [Cu(2,2'-bpy)2][Cu(2,2'
      bpy)(H2O)][Cu(pic)2]0.5[XM12O40].nH2O (X = Si, M = Mo, n = 0.5 for , X = Ge, M =
      W, n = 1 for ) and [Cu(phen)(H2O)]2[Cu(pic)2][GeW12O40].2.5H2O () (pic =
      deprotonated picolinic acid, apy = 2-aminopyridine, 2,2'-bpy = 2,2'-bipyridine,
      phen = phenanthroline), have been synthesized and characterized by IR, UV-Vis,
      XRD, cyclic voltammetric measurements and single crystal X-ray diffraction
      analysis. Single crystal X-ray analysis reveals that compounds are isomorphous
      and isostructural, in which each is based on [H2XM12O40](2-) and [Cu(pic)2].
      Compounds and are also isomorphous and isostructural, of which the structures are
      more interesting than those of compounds . Both structures are constructed from
      [XM12O40](4-) and metal mixed-organic-ligand complexes. Compound is also
      constructed from Keggin ions and metal mixed-organic-ligand complexes, which are,
      however, thoroughly different from those of compounds and . The photodegradation
      properties of compounds have been analyzed. Compounds also exhibit rapid
      absorption properties for RhB (Rhodamine B). Detailed analysis of the
      photodegradation properties of compounds reveals that the molybdate POM has
      stronger degradation ability for RhB than the tungstate one. 

PMID- 26223515
TI  - [Move to improve : New guidelines on positional therapy and early mobilization].

PMID- 26223516
TI  - Correction factors for self-selection when evaluating screening programmes.
AB  - OBJECTIVE: In screening programmes there is recognized bias introduced through
      participant self-selection (the healthy screenee bias). Methods used to evaluate
      screening programmes include Intention-to-screen, per-protocol, and the "post
      hoc" approach in which, after introducing screening for everyone, the only
      evaluation option is participants versus non-participants. All methods are prone
      to bias through self-selection. We present an overview of approaches to correct
      for this bias. METHODS: We considered four methods to quantify and correct for
      self-selection bias. Simple calculations revealed that these corrections are
      actually all identical, and can be converted into each other. Based on this,
      correction factors for further situations and measures were derived. The
      application of these correction factors requires a number of assumptions.
      RESULTS: Using as an example the German Neuroblastoma Screening Study, no
      relevant reduction in mortality or stage 4 incidence due to screening was
      observed. The largest bias (in favour of screening) was observed when comparing
      participants with non-participants. CONCLUSIONS: Correcting for bias is
      particularly necessary when using the post hoc evaluation approach, however, in
      this situation not all required data are available. External data or further
      assumptions may be required for estimation.

PMID- 26223517
TI  - Skirmish over seven day working.

PMID- 26223519
TI  - Management of sharps injuries in the healthcare setting.

PMID- 26223521
TI  - Feasibility of three wearable sensors for 24 hour monitoring in middle-aged
      women.
AB  - BACKGROUND: The purpose of this study is to determine the feasibility of three
      widely used wearable sensors in research settings for 24 h monitoring of sleep,
      sedentary, and active behaviors in middle-aged women. METHODS: Participants were
      21 inactive, overweight (M Body Mass Index (BMI) = 29.27 +/- 7.43) women, 30 to
      64 years (M = 45.31 +/- 9.67). Women were instructed to wear each sensor on the
      non-dominant hip (ActiGraph GT3X+), wrist (GENEActiv), or upper arm (BodyMedia
      SenseWear Mini) for 24 h/day and record daily wake and bed times for one week
      over the course of three consecutive weeks. Women received feedback about their
      daily physical activity and sleep behaviors. Feasibility (i.e., acceptability and
      demand) was measured using surveys, interviews, and wear time. RESULTS: Women
      felt the GENEActiv (94.7%) and SenseWear Mini (90.0%) were easier to wear and
      preferred the placement (68.4, 80% respectively) as compared to the ActiGraph
      (42.9, 47.6% respectively). Mean wear time on valid days was similar across
      sensors (ActiGraph: M = 918.8 +/- 115.0 min; GENEActiv: M = 949.3 +/- 86.6;
      SenseWear: M = 928.0 +/- 101.8) and well above other studies using wake time only
      protocols. Informational feedback was the biggest motivator, while appearance,
      comfort, and inconvenience were the biggest barriers to wearing sensors. Wear
      time was valid on 93.9% (ActiGraph), 100 % (GENEActiv), and 95.2% (SenseWear) of
      eligible days. 61.9, 95.2, and 71.4% of participants had seven valid days of data
      for the ActiGraph, GENEActiv, and SenseWear, respectively. CONCLUSION: Twenty
      four hour monitoring over seven consecutive days is a feasible approach in middle
      aged women. Researchers should consider participant acceptability and demand, in
      addition to validity and reliability, when choosing a wearable sensor. More
      research is needed across populations and study designs.

PMID- 26223520
TI  - Hypoxia inducible prolyl hydroxylase PHD3 maintains carcinoma cell growth by
      decreasing the stability of p27.
AB  - BACKGROUND: Hypoxia can halt cell cycle progression of several cell types at the
      G1/S interface. The arrest needs to be overcome by cancer cells. We have
      previously shown that the hypoxia-inducible cellular oxygen sensor PHD3/EGLN3
      enhances hypoxic cell cycle entry at the G1/S boundary. METHODS: We used PHD3
      knockdown by siRNA and shRNA in HeLa and 786-0 renal cancer cells. Flow cytometry
      with cell synchronization was used to study cell growth at different cell cycle
      phases. Total and phosphospecific antibodies together with cycloheximide chase
      were used to study p27/CDKN1B expression and fractionations for subcellular
      protein localization. RESULTS: Here we show that PHD3 enhances cell cycle by
      decreasing the expression of the CDK inhibitor p27/CDKN1B. PHD3 reduction led to
      increased p27 expression under hypoxia or VHL mutation. p27 was both required and
      sufficient for the PHD3 knockdown induced cell cycle block. PHD3 knockdown did
      not affect p27 transcription and the effect was HIF-independent. In contrast,
      PHD3 depletion increased the p27 half-life from G0 to S-phase. PHD3 depletion led
      to an increase in p27 phosphorylation at serine 10 without affecting threonine
      phosphorylation. Intact serine 10 was required for normal hypoxic and PHD3
      mediated degradation of p27. CONCLUSIONS: The data demonstrates that PHD3 can
      drive cell cycle entry at the G1/S transition through decreasing the half-life of
      p27 that occurs by attenuating p27S10 phosphorylation.

PMID- 26223522
TI  - Dynamics of mussel plaque detachment.
AB  - Mussels are well known for their ability to generate and maintain strong, long
      lasting adhesive bonds under hostile conditions. Many prior studies attribute
      their adhesive strength to the strong chemical interactions between the holdfast
      and substrate. While chemical interactions are certainly important, adhesive
      performance is also determined by contact geometry, and understanding the
      coupling between chemical interactions and the plaque shape and mechanical
      properties is essential in deploying bioinspired strategies when engineering
      improved adhesives. To investigate how the shape and mechanical properties of the
      mussel's plaque contribute to its adhesive performance, we use a custom built
      load frame capable of fully characterizing the dynamics of the detachment. With
      this, we can pull on samples along any orientation, while at the same time
      measuring the resulting force and imaging the bulk deformations of the plaque as
      well as the holdfast-substrate interface where debonding occurs. We find that the
      force-induced yielding of the mussel plaque improves the bond strength by two
      orders of magnitude and that the holdfast shape improves bond strength by an
      additional order of magnitude as compared to other simple geometries. These
      results demonstrate that optimizing the contact geometry can play as important a
      role on adhesive performance as optimizing the chemical interactions as observed
      in other organisms and model systems. 

PMID- 26223523
TI  - A realist evaluation of community-based participatory research: partnership
      synergy, trust building and related ripple effects.
AB  - BACKGROUND: Community-Based Participatory Research (CBPR) is an approach in which
      researchers and community stakeholders form equitable partnerships to tackle
      issues related to community health improvement and knowledge production. Our 2012
      realist review of CBPR outcomes reported long-term effects that were touched upon
      but not fully explained in the retained literature. To further explore such
      effects, interviews were conducted with academic and community partners of
      partnerships retained in the review. Realist methodology was used to increase the
      understanding of what supports partnership synergy in successful long-term CBPR
      partnerships, and to further document how equitable partnerships can result in
      numerous benefits including the sustainability of relationships, research and
      solutions. METHODS: Building on our previous realist review of CBPR, we contacted
      the authors of longitudinal studies of academic-community partnerships retained
      in the review. Twenty-four participants (community members and researchers) from
      11 partnerships were interviewed. Realist logic of analysis was used, involving
      middle-range theory, context-mechanism-outcome configuration (CMOcs) and the
      concept of the 'ripple effect'. RESULTS: The analysis supports the central
      importance of developing and strengthening partnership synergy through trust. The
      ripple effect concept in conjunction with CMOcs showed that a sense of trust
      amongst CBPR members was a prominent mechanism leading to partnership
      sustainability. This in turn resulted in population-level outcomes including: (a)
      sustaining collaborative efforts toward health improvement; (b) generating spin
      off projects; and (c) achieving systemic transformations. CONCLUSION: These
      results add to other studies on improving the science of CBPR in partnerships
      with a high level of power-sharing and co-governance. Our results suggest
      sustaining CBPR and achieving unanticipated benefits likely depend on trust
      related mechanisms and a continuing commitment to power-sharing. These findings
      have implications for building successful CBPR partnerships to address
      challenging public health problems and the complex assessment of outcomes.

PMID- 26223525
TI  - The detection and characterization of pleiotropy: discovery, progress, and
      promise.
AB  - The impact of a single genetic locus on multiple phenotypes, or pleiotropy, is an
      important area of research. Biological systems are dynamic complex networks, and
      these networks exist within and between cells. In humans, the consideration of
      multiple phenotypes such as physiological traits, clinical outcomes and drug
      response, in the context of genetic variation, can provide ways of developing a
      more complete understanding of the complex relationships between genetic
      architecture and how biological systems function in health and disease. In this
      article, we describe recent studies exploring the relationships between genetic
      loci and more than one phenotype. We also cover methodological developments
      incorporating pleiotropy applied to model organisms as well as humans, and
      discuss how stepping beyond the analysis of a single phenotype leads to a deeper
      understanding of complex genetic architecture. 

PMID- 26223526
TI  - A very simple and fast way to access and validate algorithms in reproducible
      research.
AB  - The reproducibility of research in bioinformatics refers to the notion that new
      methodologies/algorithms and scientific claims have to be published together with
      their data and source code, in a way that other researchers may verify the
      findings to further build more knowledge on them. The replication and
      corroboration of research results are key to the scientific process, and many
      journals are discussing the matter nowadays, taking concrete steps in this
      direction. In this journal itself, a recent opinion note has appeared
      highlighting the increasing importance of this topic in bioinformatics and
      computational biology, inviting the community to further discuss the matter. In
      agreement with that article, we would like to propose here another step into that
      direction with a tool that allows the automatic generation of a web interface,
      named web-demo, directly from source code in a simple and straightforward way. We
      believe this contribution can help make research not only reproducible but also
      more easily accessible. A web-demo associated to a published paper can accelerate
      an algorithm validation with real data, wide-spreading its use with just a few
      clicks. 

PMID- 26223524
TI  - Sucrose accumulation in sweet sorghum stems occurs by apoplasmic phloem unloading
      and does not involve differential Sucrose transporter expression.
AB  - BACKGROUND: Sorghum (Sorghum bicolor L. Moench) cultivars store non-structural
      carbohydrates predominantly as either starch in seeds (grain sorghums) or sugars
      in stems (sweet sorghums). Previous research determined that sucrose accumulation
      in sweet sorghum stems was not correlated with the activities of enzymes
      functioning in sucrose metabolism, and that an apoplasmic transport step may be
      involved in stem sucrose accumulation. However, the sucrose unloading pathway
      from stem phloem to storage parenchyma cells remains unelucidated. Sucrose
      transporters (SUTs) transport sucrose across membranes, and have been proposed to
      function in sucrose partitioning differences between sweet and grain sorghums.
      The purpose of this study was to characterize the key differences in carbohydrate
      accumulation between a sweet and a grain sorghum, to define the path sucrose may
      follow for accumulation in sorghum stems, and to determine the roles played by
      sorghum SUTs in stem sucrose accumulation. RESULTS: Dye tracer studies to
      determine the sucrose transport route revealed that, for both the sweet sorghum
      cultivar Wray and grain sorghum cultivar Macia, the phloem in the stem veins was
      symplasmically isolated from surrounding cells, suggesting sucrose was
      apoplasmically unloaded. Once in the phloem apoplasm, a soluble tracer diffused
      from the vein to stem parenchyma cell walls, indicating the lignified mestome
      sheath encompassing the vein did not prevent apoplasmic flux outside of the vein.
      To characterize carbohydrate partitioning differences between Wray and Macia, we
      compared the growth, stem juice volume, solute contents, SbSUTs gene expression,
      and additional traits. Contrary to previous findings, we detected no significant
      differences in SbSUTs gene expression within stem tissues. CONCLUSIONS: Phloem
      sieve tubes within sweet and grain sorghum stems are symplasmically isolated from
      surrounding cells; hence, unloading from the phloem likely occurs apoplasmically,
      thereby defining the location of the previously postulated step for sucrose
      transport. Additionally, no changes in SbSUTs gene expression were detected in
      sweet vs. grain sorghum stems, suggesting alterations in SbSUT transcript levels
      do not account for the carbohydrate partitioning differences between cultivars. A
      model illustrating sucrose phloem unloading and movement to stem storage
      parenchyma, and highlighting roles for sucrose transport proteins in sorghum
      stems is discussed.

PMID- 26223527
TI  - Adult degenerative scoliosis associated with increased aortic diameter and plaque
      burden and composition.
AB  - OBJECTIVE: In this study, we aimed to investigate the relationship between adult
      degenerative scoliosis (ADS) and the aortic plaques and diameters. METHOD: We
      included 219 patients with ADS and 100 control patients without ADS. Diameters of
      ascending, arch, descending and abdominal aorta and number, localization and
      types of the aortic plaques, and the Cobb angles of all patients were measured
      from computed tomography (CT) images. We divided the patients with ADS into three
      groups according to the Cobb angle, and divided them into four groups according
      to level of spine deformity. RESULTS: The patients with ADS had a larger aorta
      and more aortic plaques (both, p < 0.001). The patients with ADS had more fibro
      fatty and mix plaques (both, p < 0.001). The patients with severe ADS had larger
      diameters of the ascending and arch of the aorta (p = 0.026 and p = 0.027,
      respectively). The patients with the main thoracic curve had a larger ascending
      aorta and the patients with a thoracolumbar curve had more aortic plaques (p =
      0.035 and p = 0.029, respectively). In multivariate regression analysis, the ADS
      was an independent risk factor for both aortic dilatation (>3.6 cm) and aortic
      plaque build-up (both, p < 0.001). CONCLUSION: The ADS may be a risk factor for
      aortic dilatation and aortic atherosclerosis.

PMID- 26223528
TI  - Elective endovascular vs. open repair for abdominal aortic aneurysm in
      octogenarians.
AB  - PURPOSE: The purpose of this study was to investigate the operative mortality and
      short-term and midterm outcomes of treatment of abdominal aortic aneurysm in
      Japanese patients over 80 years of age. METHODS: Between January 2007 and
      December 2011, 207 patients underwent elective repair of infrarenal abdominal
      aortic aneurysms. Comorbidities, operative morbidity and mortality, midterm
      outcomes were analyzed retrospectively. RESULTS: The average age (endovascular
      aneurysm repair, 84.4 +/- 0.3; open, 82.8 +/- 0.3, P < 0.01) and the percentage
      of hostile abdomen (endovascular aneurysm repair, 22.2%; open repair, 11.1%, P <
      0.05) were higher in the endovascular aneurysm repair group. Percentage of
      outside IFU was higher in open repair (endovascular aneurysm repair, 38.5%; open
      repair, 63.3%, P < 0.01). The cardiac complication (endovascular aneurysm repair,
      0%; open repair, 5.6%, P < 0.01) and length of postoperative hospital stay
      (endovascular aneurysm repair, 10.3 +/- 0.8 days; open, 18.6 +/- 1.6 days, P <
      0.05) were significantly lower in the endovascular aneurysm repair group. There
      were no differences in operative mortality (endovascular aneurysm repair, 0%;
      open, 1.1%, P = 0.43) and the aneurysm-related death was not observed. The rate
      of secondary interventions (EVAR, 5.1%; open repair, 0%, P < 0.01) and midterm
      mortality rate were much higher in the endovascular aneurysm repair group.
      CONCLUSIONS: Endovascular aneurysm repair is less invasive than open repair and
      useful for treating abdominal aortic aneurysm in octogenarians; however, open
      repair can be acceptable treatment in the inappropriate case treated by
      endovascular aneurysm repair.

PMID- 26223529
TI  - Distal bypass to a critically ischemic foot increases the skin perfusion pressure
      at the opposite site of the distal anastomosis.
AB  - INTRODUCTION: The purpose of the study was to reveal the effect of blood flow
      supply to the foot by analyzing the skin perfusion pressure values and the pedal
      arch connection after bypass surgery. PATIENTS AND METHODS: We selected 48
      operated limbs whose skin perfusion pressure was measured pre- and post
      operatively on the opposite site of distal anastomosis. We also assigned the
      ischemic limbs to three groups according to the patency of the pedal arch: good,
      intermediate, and poor. RESULTS: The mean value of skin perfusion pressure
      increased significantly from 27.0 +/- 14.9 to 52.8 +/- 16.0 (p < 0.001) post
      operatively. Skin perfusion pressure improved in most of the limbs post
      operatively and decreased or unchanged in only four limbs, all of which showed
      improved tissue loss. Three amputated limbs were due to infection, and all showed
      an increase in skin perfusion pressure. CONCLUSION: It was difficult to correlate
      limb prognosis to skin perfusion pressure and the pedal arch connection.

PMID- 26223530
TI  - Comment on "The value of a new image classification system for planning treatment
      and prognosis of spontaneous isolated superior mesenteric artery dissection".

PMID- 26223531
TI  - Aortic aneurysm trials in octogenarians: Are we really measuring the outcomes
      that matter?
AB  - PURPOSE: This study is a systematic review to determine the types of outcomes
      reported in abdominal aortic aneurysm (AAA) studies of patients aged 80 and over.
      Specifically, it determines the types of patient-centered outcomes reported.
      METHOD: MEDLINE and EMBASE were searched from 2000 to 2014 for studies on AAA
      surgery with outcome data on patients aged 80 and over. Outcomes were categorized
      according to Donabedian's framework for health quality indicators, with further
      classification as procedural, complication, resource or patient-centered outcome
      indicators. FINDINGS: Forty studies were reviewed. Patient-centered outcomes were
      infrequently reported (13%, n=5), with limited outcomes specifically relevant to
      older patients. No studies reported physical function, activities of daily living
      or cognition using validated assessment methods. Short-term mortality (95%, n=38)
      and complications (85%, n=34) were reported most frequently. CONCLUSION:
      Reporting of aortic surgery outcomes in patients aged 80 and over requires a
      focus upon outcomes of primary importance to people of this age.

PMID- 26223532
TI  - Heparin-free continuous vena-venous hemofiltration as a veno-venous bypass in
      inferior vena cava reconstruction.
AB  - OBJECTIVE: This paper investigated the effects of continuous vena-venous
      hemofiltration on inferior vena cava reconstruction. METHOD: Totally, 11 patients
      were observed, vascular access in right internal jugular vein and femoral vein
      catheterization was established guided by ultrasound, and heparin-free continuous
      vena-venous hemofiltration was used to substitute for extracorporeal veno-venous
      bypass. Furthermore, blood pressure, central venous pressure, urine volume, blood
      platelet, serum albumin, renal function, serum cystatin C, CRP, TBil, AST, ALT,
      serum amylase, serum lipase, PLT, PT, APTT, Fig, D-mier, and adverse events were
      determined. RESULTS: All operations were completed successfully. Average time of
      continuous vena-venous hemofiltration was 2.96 +/- 0.76 h. No hematoma and blood
      leakage was occurred when catheters were inserted, and no luminal stenosis and
      catheter-related infections were observed. Visceral congestion was observed when
      the inferior vena cava was clamped, but significantly improved immediately after
      the continuous vena-venous hemofiltration was begun. No hemofilter was changed
      due to clotting during continuous vena-venous hemofiltration therapy. Blood
      pressure, central venous pressure, and urine volume of the patients maintained
      stable. No significant change was observed in blood platelet, serum albumin, and
      serum creatinin. Serum cystatin and hsCRP increased after operation, but still in
      normal level. CONCLUSION: Heparin-free continuous vena-venous hemofiltration was
      an effective mode as veno-venous bypass in the treatment of inferior vena cava
      interruption and reconstruction.

PMID- 26223533
TI  - Aneurysm of an aberrant splenic artery: An extremely rare occurrence.
AB  - An aberrant splenic artery arising from the superior mesenteric artery, also
      known as the splenomesenteric trunk, is a rare anatomical variant seen in less
      than 1% of the population and is more common in females. Aneurysms of the splenic
      artery originating anomalously from the superior mesenteric artery are extremely
      rare; only 35 cases of aneurysm of an aberrant splenic artery have been described
      so far in the English medical literature. We report an extremely rare case of
      aneurysm of aberrant splenic artery in a 28-year-old man in whom the lesion was
      detected during routine abdominal scanning and confirmed on computed tomography
      angiography. Aneurysms of an anomalous splenic artery originating from the
      superior mesenteric artery are extremely rare; however, they are clinically
      important because possible rupture could be catastrophic. Exploring these
      variations is important especially if surgical intervention is contemplated. This
      could greatly affect the surgical planning and avoid injuries to major arteries
      and organs intraoperatively. 

PMID- 26223534
TI  - Coming to terms with chromatin structure.
AB  - Chromatin, once thought to serve only as a means to package DNA, is now
      recognized as a major regulator of gene activity. As a result of the wide range
      of methods used to describe the numerous levels of chromatin organization, the
      terminology that has emerged to describe these organizational states is often
      imprecise and sometimes misleading. In this review, we discuss our current
      understanding of chromatin architecture and propose terms to describe the various
      biochemical and structural states of chromatin. 

PMID- 26223535
TI  - Independent validation test of the vote-counting strategy used to rank biomarkers
      from published studies.
AB  - AIM: Vote counting is frequently used in meta-analyses to rank biomarker
      candidates, but to our knowledge, there have been no independent assessments of
      its validity. Here, we used predictions from a recent meta-analysis to determine
      how well number of supporting studies, combined sample size and mean fold change
      performed as vote-counting strategy criteria. MATERIALS & METHODS: Fifty miRNAs
      previously ranked for their ability to distinguish lung cancer tissue from normal
      were assayed by RT-qPCR using 45 paired tumor-normal samples. RESULTS: Number of
      supporting studies predicted biomarker performance (p = 0.0006; r = 0.44), but
      sample size and fold change did not (p > 0.2). CONCLUSION: Despite limitations,
      counting the number supporting studies appears to be an effective criterion for
      ranking biomarkers. Predictions based on sample size and fold change provided
      little added value. External validation studies should be conducted to establish
      the performance characteristics of strategies used to rank biomarkers.

PMID- 26223537
TI  - Nonbullous Erythema Multiforme in Hospitalized Children: A 10-Year Survey.
AB  - BACKGROUND: Nonbullous erythema multiforme (NBEM) is an acute, immune-mediated,
      self-limiting skin disease with distinctive target lesions. Its pathogenesis is
      unclear, but most cases are considered to be infection related or drug related.
      In adults, the main precipitating factor is infection. This study reviewed a 10
      year experience with hospitalized children with NBEM in a tertiary pediatric
      medical center in Israel with a focus on precipitating factors. METHODS: The
      medical files of all children hospitalized from 2001 to 2011 with the diagnosis
      of NBEM were reviewed. RESULTS: Ninety-seven patients (55 boys and 42 girls) met
      the inclusion criteria. The mean age was 4.0 years. At least one precipitating
      factor was recognized in 72 cases; the remainders were classified as idiopathic.
      The most common factor was drugs (n = 45), particularly penicillin (n = 30),
      followed by infection with various pathogens (n = 27) including Epstein-Barr
      virus (7), group A Streptococcus (n = 6), Mycoplasma pneumoniae (n = 5) and
      herpes simplex virus (n = 4). Analysis according to age showed that medication
      was the most common precipitating factor in the first year of life, and infection
      was as common as drugs in the older age groups (1-18 years). CONCLUSIONS: Unlike
      adult NBEM, the majority of pediatric NBEM is associated with medications,
      especially penicillin. This may be due to the frequent use of antibiotics in
      children.

PMID- 26223536
TI  - Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic
      association study, meta-analysis and geo-epidemiological investigation.
AB  - INTRODUCTION: Giant cell arteritis (GCA) is an autoimmune disease commonest in
      Northern Europe and Scandinavia. Previous studies report various associations
      with HLA-DRB1*04 and HLA-DRB1*01; HLA-DRB1 alleles show a gradient in population
      prevalence within Europe. Our aims were (1) to determine which amino acid
      residues within HLA-DRB1 best explained HLA-DRB1 allele susceptibility and
      protective effects in GCA, seen in UK data combined in meta-analysis with
      previously published data, and (2) to determine whether the incidence of GCA in
      different countries is associated with the population prevalence of the HLA-DRB1
      alleles that we identified in our meta-analysis. METHODS: GCA patients from the
      UK GCA Consortium were genotyped by using single-strand oligonucleotide
      polymerization, allele-specific polymerase chain reaction, and direct sequencing.
      Meta-analysis was used to compare and combine our results with published data,
      and public databases were used to identify amino acid residues that may explain
      observed susceptibility/protective effects. Finally, we determined the
      relationship of HLA-DRB1*04 population carrier frequency and latitude to GCA
      incidence reported in different countries. RESULTS: In our UK data (225 cases and
      1378 controls), HLA-DRB1*04 carriage was associated with GCA susceptibility (odds
      ratio (OR) = 2.69, P = 1.5*10(-11)), but HLA-DRB1*01 was protective (adjusted OR
      = 0.55, P = 0.0046). In meta-analysis combined with 14 published studies (an
      additional 691 cases and 4038 controls), protective effects were seen from HLA
      DR2, which comprises HLA-DRB1*15 and HLA-DRB1*16 (OR = 0.65, P = 8.2*10(-6)) and
      possibly from HLA-DRB1*01 (OR = 0.73, P = 0.037). GCA incidence (n = 17
      countries) was associated with population HLA-DRB1*04 allele frequency (P =
      0.008; adjusted R(2) = 0.51 on univariable analysis, adjusted R(2) = 0.62 after
      also including latitude); latitude also made an independent contribution.
      CONCLUSIONS: We confirm that HLA-DRB1*04 is a GCA susceptibility allele. The
      susceptibility data are best explained by amino acid risk residues V, H, and H at
      positions 11, 13, and 33, contrary to previous suggestions of amino acids in the
      second hypervariable region. Worldwide, GCA incidence was independently
      associated both with population frequency of HLA-DRB1*04 and with latitude
      itself. We conclude that variation in population HLA-DRB1*04 frequency may partly
      explain variations in GCA incidence and that HLA-DRB1*04 may warrant
      investigation as a potential prognostic or predictive biomarker.

PMID- 26223538
TI  - Variation in hospital caesarean section rates for preterm births.
AB  - BACKGROUND: Evidence about optimal mode of delivery for preterm birth is lacking,
      and there is thought to be considerable variation in practice. OBJECTIVE: To
      assess whether variation in hospital preterm caesarean section rates (Robson
      Classification Group 10) and outcomes are explained by casemix, labour or
      hospital characteristics. MATERIALS AND METHODS: Population-based cohort study in
      NSW, 2007-2011. Births were categorised according to degree of prematurity and
      hospital service capability: 26-31, 32-33 and 34-36 weeks' gestation. Hospital
      preterm caesarean rates were investigated using multilevel logistic regression
      models, progressively adjusting for casemix, labour and hospital factors. The
      association between hospital caesarean rates, and severe maternal and neonatal
      morbidity rates was assessed. RESULTS: At 26-31 weeks' gestation, the caesarean
      rate was 55.2% (seven hospitals, range 43.4-58.4%); 50.9% at 32-33 weeks (12
      hospitals, 43.4-58.1%); and 36.4% at 34-36 weeks (51 hospitals, 17.4-48.3%). At
      26-31 weeks and 32-33 weeks' gestation, 81% and 59% of the variation between
      hospitals was explained with no hospital significantly different from the state
      average after adjustment. At 34-36 weeks' gestation, although 59% of the
      variation was explained, substantial unexplained variation persisted. Hospital
      caesarean rates were not associated with severe maternal morbidity rates at any
      gestational age. At 26-31 weeks' gestation, medium and high caesarean rates were
      associated with higher severe neonatal morbidity rates, but there was no evidence
      of this association >=32 weeks. CONCLUSION: Both casemix and practice differences
      contributed to the variation in hospital caesarean rates. Low preterm caesarean
      rates were not associated with worse outcomes.

PMID- 26223539
TI  - Mixed Linear Model Approaches of Association Mapping for Complex Traits Based on
      Omics Variants.
AB  - Precise prediction for genetic architecture of complex traits is impeded by the
      limited understanding on genetic effects of complex traits, especially on gene-by
      gene (GxG) and gene-by-environment (GxE) interaction. In the past decades, an
      explosion of high throughput technologies enables omics studies at multiple
      levels (such as genomics, transcriptomics, proteomics, and metabolomics). The
      analyses of large omics data, especially two-loci interaction analysis, are very
      time intensive. Integrating the diverse omics data and environmental effects in
      the analyses also remain challenges. We proposed mixed linear model approaches
      using GPU (Graphic Processing Unit) computation to simultaneously dissect various
      genetic effects. Analyses can be performed for estimating genetic main effects,
      GxG epistasis effects, and GxE environment interaction effects on large-scale
      omics data for complex traits, and for estimating heritability of specific
      genetic effects. Both mouse data analyses and Monte Carlo simulations
      demonstrated that genetic effects and environment interaction effects could be
      unbiasedly estimated with high statistical power by using the proposed
      approaches. 

PMID- 26223540
TI  - Home-based HIV testing for men preferred over clinic-based testing by pregnant
      women and their male partners, a nested cross-sectional study.
AB  - BACKGROUND: Male partner HIV testing and counseling (HTC) is associated with
      enhanced uptake of prevention of mother-to-child HIV transmission (PMTCT), yet
      male HTC during pregnancy remains low. Identifying settings preferred by pregnant
      women and their male partners may improve male involvement in PMTCT. METHODS:
      Participants in a randomized clinical trial (NCT01620073) to improve male partner
      HTC were interviewed to determine whether the preferred male partner HTC setting
      was the home, antenatal care (ANC) clinic or VCT center. In this nested cross
      sectional study, responses were evaluated at baseline and after 6 weeks.
      Differences between the two time points were compared using McNemar's test and
      correlates of preference were determined using logistic regression. RESULTS:
      Among 300 pregnant female participants, 54% preferred home over ANC clinic
      testing (34.0%) or VCT center (12.0%). Among 188 male partners, 68% preferred
      home-based HTC to antenatal clinic (19%) or VCT (13%). Men who desired more
      children and women who had less than secondary education or daily income < $2 USD
      were more likely to prefer home-based over other settings (p < 0.05 for all
      comparisons). At 6 weeks, the majority of male (81%) and female (65%)
      participants recommended home over alternative HTC venues. Adjusting for whether
      or not the partner was tested during follow-up did not significantly alter
      preferences. CONCLUSIONS: Pregnant women and their male partners preferred home
      based compared to clinic or VCT-center based male partner HTC. Home-based HTC
      during pregnancy appears acceptable and may improve male testing and involvement
      in PMTCT.

PMID- 26223542
TI  - Effects of anatomic characteristics of aneurysms on packing density in
      endovascular coil embolization: analysis of a single center's experience.
AB  - When embolizing cerebral aneurysms, dense coil packing may prevent recanalization
      but this may be influenced by the aneurysm morphology. We have analyzed
      retrospectively the relationship between anatomic features and the volumetric
      coil packing density. We analyzed 452 aneurysms in 434 patients treated by coil
      embolization without stenting, expressing packing density as volume embolization
      ratio (VER, volume of inserted coils/aneurysm volume). Six morphological
      variables (neck width, height, maximum diameter, dome to neck ratio (DNR), and
      aspect ratio), aneurysm location, and whether the aneurysm was ruptured or
      unruptured were analyzed with respect to dense (VER >=20%) or loose (VER <20%)
      packing densities, using logistic regression analysis and ROC analysis. Among 452
      aneurysms, VERs >20% were achieved for 272 aneurysms, with a mean VER of 24.7%.
      The mean VER of the remaining 180 aneurysms was 15.6%. In univariate analyses,
      the predictors for dense packing were having an anterior circulation, DNR, aspect
      ratio, and neck width. In multivariate analysis, the independent predictors were
      smaller neck width (odds ratio (OR) 0.8735; 95% confidence interval (CI) 0.7635
      0.9993) and larger aspect ratio (OR 1.6679; 95% CI 1.0460-2.6594). ROC analysis
      showed optimal cutoff values for an aspect ratio of 1.35 (sensitivity 69.5%,
      specificity 51.7%) and a neck width of 3.13 mm (sensitivity 51.1%, specificity
      27.8%). Although dense coil packing is still difficult to achieve in wide-necked
      aneurysms without the use of stents, packing with VER >20% is expected to be
      achieved when the height is 1.35 times larger than the neck width.

PMID- 26223541
TI  - Orexin receptors exert a neuroprotective effect in Alzheimer's disease (AD) via
      heterodimerization with GPR103.
AB  - Orexins are neuropeptides that regulate the sleep-wake cycle and feeding
      behaviour. QRFP is a newly discovered neuropeptide which exerts similar
      orexigenic activity, thus playing an important role in energy homeostasis and
      regulation of appetite. The exact expression and signalling characteristics and
      physiological actions of QRFP and its receptor GPR103 are poorly understood.
      Alzheimer's disease (AD) patients experience increased nocturnal activity,
      excessive daytime sleepiness, and weight loss. We hypothesised therefore that
      orexins and QRFP might be implicated in the pathophysiology of AD. We report that
      the down-regulation of hippocampal orexin receptors (OXRs) and GPR103
      particularly in the cornu ammonis (CA) subfield from AD patients suffering from
      early onset familial AD (EOFAD) and late onset familial AD (LOAD). Using an in
      vitro model we demonstrate that this downregulation is due to to Abeta-plaque
      formation and tau hyper-phosphorylation. Transcriptomics revealed a
      neuroprotective role for both orexins and QRFP. Finally we provide conclusive
      evidence using BRET and FRET that OXRs and GPR103 form functional hetero-dimers
      to exert their effects involving activation of ERK1/2. Pharmacological
      intervention directed at the orexigenic system may prove to be an attractive
      avenue towards the discovery of novel therapeutics for diseases such as AD and
      improving neuroprotective signalling pathways. 

PMID- 26223544
TI  - Examining the Efficiency of Models Using Tangent Coordinates or Principal
      Component Scores in Allometry Studies.
AB  - Most of the studies in medical and biological sciences are related to the
      examination of geometrical properties of an organ or organism. Growth and
      allometry studies are important in the way of investigating the effects of
      diseases and the environmental factors effects on the structure of the organ or
      organism. Thus, statistical shape analysis has recently become more important in
      the medical and biological sciences. Shape is all geometrical information that
      remains when location, scale and rotational effects are removed from an object.
      Allometry, which is a relationship between size and shape, plays an important
      role in the development of statistical shape analysis. The aim of the present
      study was to compare two different models for allometry which includes tangent
      coordinates and principal component scores of tangent coordinates as dependent
      variables in multivariate regression analysis. The results of the simulation
      study showed that the model constructed by taking tangent coordinates as
      dependent variables is more appropriate than the model constructed by taking
      principal component scores of tangent coordinates as dependent variables, for all
      sample sizes. 

PMID- 26223543
TI  - A Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Adalimumab in
      Pediatric Patients With Enthesitis-Related Arthritis.
AB  - OBJECTIVE: Enthesitis-related arthritis (ERA) is a juvenile idiopathic arthritis
      (JIA) category, primarily affecting entheses and peripheral joints. This study
      evaluated efficacy, safety, and pharmacokinetics of adalimumab versus placebo in
      patients with ERA. METHODS: This is a phase III, multicenter, randomized double
      blind study in patients ages >=6 to <18 years with ERA treated with adalimumab
      (24 mg/m(2) , maximum dose 40 mg every other week) or placebo for 12 weeks,
      followed by up to 192 weeks of open-label adalimumab. The primary end point was
      percent change from baseline in number of active joints with arthritis (AJC) at
      week 12. Samples were collected to determine adalimumab serum concentrations.
      Adverse events (AEs) were assessed throughout the study. RESULTS: Forty-six
      patients were randomized (31 adalimumab/15 placebo). At baseline, mean age was
      12.9 years, mean duration of ERA symptoms was 2.6 years, mean AJC was 7.8, and
      mean enthesitis count was 8.1. Mean percent change from baseline in AJC at week
      12 was greater in the adalimumab group versus placebo (-62.6% versus -11.6%; P =
      0.039). Most secondary variables favored adalimumab versus placebo at week 12.
      Treatment response further increased with continued adalimumab therapy through
      week 52. Mean steady-state adalimumab serum concentrations were 7.5-11.8 MUg/ml,
      similar to patients age >=2 years with polyarticular JIA. AE rates were similar
      between placebo and adalimumab: any AE (53.3% versus 67.7%), serious AEs (0%
      versus 3.2%), and infectious AEs (20.0% versus 29.0%). CONCLUSION: Adalimumab
      reduced signs and symptoms of ERA at week 12, with improvement sustained through
      week 52. The safety profile was consistent with previous adalimumab studies.

PMID- 26223545
TI  - Design of Potential RNAi (miRNA and siRNA) Molecules for Middle East Respiratory
      Syndrome Coronavirus (MERS-CoV) Gene Silencing by Computational Method.
AB  - The Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that
      manifests itself in viral infection with fever, cough, shortness of breath, renal
      failure and severe acute pneumonia, which often result in a fatal outcome. MERS
      CoV has been shown to spread between people who are in close contact.
      Transmission from infected patients to healthcare personnel has also been
      observed and is irredeemable with present technology. Genetic studies on MERS-CoV
      have shown that ORF1ab encodes replicase polyproteins and play a foremost role in
      viral infection. Therefore, ORF1ab replicase polyprotein may be used as a
      suitable target for disease control. Viral activity can be controlled by RNA
      interference (RNAi) technology, a leading method for post transcriptional gene
      silencing in a sequence-specific manner. However, there is a genetic
      inconsistency in different viral isolates; it is a great challenge to design
      potential RNAi (miRNA and siRNA) molecules which can silence the respective
      target genes rather than any other viral gene simultaneously. In the current
      study, four effective miRNA and five siRNA molecules for silencing of nine
      different strains of MERS-CoV were rationally designed and corroborated using
      computational methods, which might lead to knockdown the activity of virus. siRNA
      and miRNA molecules were predicted against ORF1ab gene of different strains of
      MERS-CoV as effective candidate using computational methods. Thus, this method
      may provide an insight for the chemical synthesis of antiviral RNA molecule for
      the treatment of MERS-CoV, at genomic level. 

PMID- 26223546
TI  - Design and Implementation of a Telecardiology System for Mobile Devices.
AB  - This paper presents the design and implementation of a system for digital
      telecardiology on mobile devices called Remote Cardio Consultation (RCC). Using
      RCC may improve first intervention procedures in case of heart attack. In fact,
      it allows physicians to remotely consult ECG signals from a mobile device or
      smartphone by using a so-called app. The remote consultation is implemented by a
      server application collecting physician availability to answer upon client
      support requests. The app can be used by first intervention clinicians and allows
      reducing delays and decision errors in emergency interventions. Thus, best
      decision, certified and supported by cardiologists, can be obtained in case of
      heart attacks and first interventions even by base medical doctors able to
      produce and send an ECG. RCC tests have been performed, and the prototype is
      freely available as a service for testing. 

PMID- 26223547
TI  - In Silico Analysis of Sequence-Structure-Function Relationship of the Escherichia
      coli Methionine Synthase.
AB  - The molecular evolution of various metabolic pathways in the organisms can be
      employed for scrutinizing the molecular aspects behind origin of life. In the
      present study, we chiefly concerned about the sequence-structure-function
      relationship between the Escherichia coli methionine synthase and their
      respective animal homologs by in silico approach. Using homology prediction
      technique, it was observed that only 79 animal species showed similarity with the
      E. coli methionine synthase. Also, multiple sequence alignment depicted only 25
      conserved patterns between the E. coli methionine synthase and their respective
      animal homologs. Based on that, Pfam analysis identified the protein families of
      22 conserved patterns among the attained 25 conserved patterns. Furthermore, the
      3D structure was generated by HHpred and evaluated by corresponding Ramachandran
      plot specifying 93% of the phi and psi residues angles in the most ideal regions.
      Hence, the designed structure was established as a good quality model for the
      full length of E. coli methionine synthase.

PMID- 26223548
TI  - Ultrastructural Visualization of Vaccine Adjuvant Uptake In Vitro and In Vivo.
AB  - Adjuvants are substances that enhance adaptive immune responses when formulated
      in a vaccine. Alum and MF59 are two vaccine adjuvants licensed for human
      vaccination. Their mode of action has not been completely elucidated. Here we
      show the first ultrastructural visualization of Alum and MF59 interaction with
      immune cells in vitro and in vivo. We observed that Alum is engulfed by cells as
      inclusions of laminae that are detectable within draining lymph nodes. MF59 is
      instead engulfed by cells in vitro as low-electron-dense lipid-like inclusions
      that display a vesicle pattern, as confirmed by confocal microscopy using
      fluorescently labeled MF59. However, lipid-like inclusions with different high-
      and low-electron-dense content are detected within cells of draining lymph nodes
      when injecting MF59. As high-electron-dense lipid-like inclusions are also
      detected upon injection of Alum, our results suggest that the low-electron-dense
      inclusions are formed by engulfed MF59, whereas the high-electron-dense
      inclusions are proper lipid inclusions. Thus, we demonstrated that vaccine
      adjuvants are engulfed as inclusions by lymph node cells and hypothesize that
      adjuvant treatment may modify lipid metabolism. 

PMID- 26223549
TI  - Voltage and Dopant Concentration Measurements of Semiconductors using a Band-Pass
      Toroidal Energy Analyzer Inside a Scanning Electron Microscope.
AB  - This paper presents experimental results obtained from a scanning electron
      microscope (SEM) second-order focusing toroidal electron energy analyzer
      attachment. The results demonstrate that the analyzer can be used to obtain high
      signal-to-noise voltage and dopant concentration measurements on semiconductors
      in the presence of different electric field conditions at the sample. The
      experimentally calculated relative error of measurement typically varies from 31
      to 63, corresponding to secondary electron (SE) signal mean shifts of 9-18 mV.
      The millivolt accuracy of these results is over one order of magnitude better
      than earlier quantitative dopant concentration measurements made by a retarding
      field analyzer. 

PMID- 26223551
TI  - Theory and New Applications of Ex Situ Lift Out.
AB  - The ex situ lift out (EXLO) adhesion forces are reviewed and new applications of
      EXLO for focused ion beam (FIB)-prepared specimens are described. EXLO is used to
      manipulate electron transparent specimens on microelectromechanical systems
      carrier devices designed for in situ electron microscope analysis. A new patented
      grid design without a support film is described for EXLO. This new slotted grid
      design provides a surface for holding the specimen in place and also allows for
      post lift out processing. Specimens may be easily manipulated into a backside
      orientation to reduce FIB curtaining artifacts with this slotted grid. Large EXLO
      specimens can be manipulated from Xe+ plasma FIB prepared specimens. Finally,
      applications of EXLO and manipulation of FIB specimens using a vacuum probe lift
      out method are shown. The vacuum probe provides more control for placing
      specimens on the new slotted grids and also allows for easy manipulation into a
      backside configuration. 

PMID- 26223550
TI  - Multiplexed TEM Specimen Preparation and Analysis of Plasmonic Nanoparticles.
AB  - We describe a system for rapidly screening hundreds of nanoparticle samples using
      transmission electron microscopy (TEM). The system uses a liquid handling robot
      to place up to 96 individual samples onto a single standard TEM grid at separate
      locations. The grid is then transferred into the TEM and automated software is
      used to acquire multiscale images of each sample. The images are then analyzed to
      extract metrics on the size, shape, and morphology of the nanoparticles. The
      system has been used to characterize plasmonically active nanomaterials. 

PMID- 26223552
TI  - Comparison of mechanical parameters between tissue-engineered and native
      cartilage: a numerical study.

PMID- 26223553
TI  - Exploring How Knowledge Translation Can Improve Sustainability of Community-based
      Health Initiatives for People with Intellectual/Developmental Disabilities.
AB  - Community-based health initiatives (CBHI) play an important role in maintaining
      the health, function and participation of people with intellectual/developmental
      disabilities (I/DD) living in the community. However, implementation and long
      term sustainability of CBHI is challenging. The Promoting Action on Research
      Implementation in Health Services (PARiHS) is a knowledge translation (KT)
      framework that is particularly relevant to intellectual/developmental
      disabilities research as it identifies the barriers and facilitators of
      implementation and action plans. This framework provides a foundation for
      understanding how KT can be used to aid the implementation and sustainability of
      CBHI for people with intellectual/developmental disabilities. The following study
      explores how KT - specifically the PARiHS framework - can be used to help sustain
      CBHI for people with intellectual/developmental disabilities. 

PMID- 26223554
TI  - Comparison of CT-based volumetric dosimetry with traditional prescription points
      in the treatment of cervical cancer with PDR brachytherapy.
AB  - INTRODUCTION: The traditional use of two-dimensional geometric prescription
      points in intracavitary brachytherapy planning for locally advanced cervical
      cancer is increasingly being replaced by three-dimensional (3D) planning. This
      study aimed to directly compare the two planning methods to validate that CT
      planning provides superior dosimetry for both tumour and organs at risk (OARs) in
      our department. METHODS: The CT planning data of 10 patients with locally
      advanced cervical cancer was audited. For each CT dataset, two new brachytherapy
      plans were created, comparing the dosimetry of conventional American
      Brachytherapy Society points and 3D-optimised volumes created for the high-risk
      clinical target volume (HR CTV) and OARs. Total biologically equivalent doses for
      these structures were calculated using the modified EQD2 formula and comparative
      dose-volume histogram (DVH) analysis performed. RESULTS: DVH analysis revealed
      that for the 3D-optimised plans, the prescription aim of D90 >= 100% was achieved
      for the HR CTV in all 10 patients. However, when prescribing to point A, only 50%
      of the plans achieved the minimum required dose to the HR CTV. Rectal and bladder
      dose constraints were met for all 3D-optimised plans but exceeded in two and one
      of the conventional plans, respectively. CONCLUSIONS: This study confirms that
      the regionally relevant practice of CT-based 3D-optimised planning results in
      improved tumour dose coverage compared with traditional points-based planning
      methods and also improves dose to the rectum and bladder.

PMID- 26223556
TI  - Moving forward with article level metrics: introducing altmetrics.

PMID- 26223555
TI  - Carbohydrate-binding modules influence substrate specificity of an endoglucanase
      from Clostridium thermocellum.
AB  - Most cellulases contain carbohydrate-binding modules (CBMs) that largely
      contribute to their activity for insoluble substrates. Clostridium thermocellum
      Cel5E is an endoglucanase having xylanolytic activity. The Cel5E originally has a
      family 11 CBM preferentially binding to beta-1,4- and beta-1,3-1,4-mixed linkage
      glucans. In this study, we replaced the CBM with a different type of CBM, either
      a family 3 microcrystalline cellulose-directed CBM from Clostridium josui
      scaffoldin, or a family 6 xylan-directed CBM from Clostridium stercorarium
      xylanase 11A. Chimeric endoglucanases showed enhanced activity that was affected
      by CBM binding specificity. These chimeric enzymes could efficiently degrade
      milled lignocellulosic materials, such as corn hulls, because of heterologous
      components in the plant cell wall, indicating that diverse CBMs play roles in
      degradation of lignocellulosic materials.

PMID- 26223557
TI  - Erectile dysfunction and its detection in the healthcare setting: 10 years on.

PMID- 26223558
TI  - Pneumococcal pneumonia and risk of acute pancreatitis.

PMID- 26223559
TI  - Author's reply to pneumococcal pneumonia and risk of acute pancreatitis.

PMID- 26223560
TI  - Using a participatory action research framework to listen to Aboriginal and
      Torres Strait Islander people in Australia about pandemic influenza.
AB  - INTRODUCTION: This article describes the use and effectiveness of the
      participatory action research (PAR) framework to better understand community
      members' perceptions and risks of pandemic influenza. In 2009, the H1N1 influenza
      pandemic affected Indigenous populations more than non-Indigenous populations in
      Oceania and the Americas. Higher prevalence of comorbidities (diabetes, obesity,
      asthma and chronic obstructive pulmonary disease) as well as pregnancy in
      Indigenous communities may have contributed to the higher risks of severe
      disease. Social disparity, institutionalised racism within health services and
      differences in access to culturally safe health services have also been reported
      as contributors to disadvantage and delayed appropriate treatment. METHODS: Given
      these factors and the subsequent impact they had on Australian Aboriginal and
      Torres Strait Islander communities, the authors set out to ensure that the
      Australian national, state and territory pandemic plans adequately reflected the
      risk status of Aboriginal and Torres Strait Islander peoples and promoted
      meaningful engagement with communities to mitigate this risk. A national study
      explored the views of Aboriginal and Torres Strait Islander people and their
      experiences with H1N1 and used a qualitative PAR framework that was effective in
      gaining deep understandings from participants. Aboriginal and Torres Strait
      Islander community-controlled organisations and health services were involved in
      the implementation, interpretation and monitoring of this project. RESULTS: As a
      result, important features of the implementation of this PAR framework with
      Aboriginal and Torres Strait Islander communities and organisations emerged.
      These features included the importance of working in a multidisciplinary team
      with Aboriginal and Torres Strait Islander researchers; the complexities and
      importance of obtaining multi-site human research ethics approval processes; the
      importance and value of building the research capacity of both experienced and
      novice researchers in PAR; the need to use localised sampling protocols; and the
      process of undertaking a collective research process and enacting action research
      and feedback. CONCLUSIONS: The most effective responses of this project were
      embedded in pre-existing relationships with individuals within organisations that
      had been established over a long period of time between Aboriginal medical
      services and investigators; however, research relationships established
      specifically for the purposes of the project were less successful because of
      changes in personnel and organisational support. The participatory approach used
      in this study has the potential to be applied to vulnerable populations in other
      countries.

PMID- 26223561
TI  - Familial colorectal cancer risk may be lower than previously thought: a Danish
      cohort study.
AB  - BACKGROUND: The risk of colorectal cancer (CRC) is reportedly increased two-fold
      if at least one first-degree relative (FDR) is affected with CRC, increasing to
      three- to four-fold if multiple FDRs are affected or if one FDR was diagnosed at
      a young age. We evaluated familial risk of CRC, systematically excluding
      monogenetic high-risk families with polyposis or Lynch syndrome/hereditary non
      polyposis colorectal cancer (HNPCC). METHODS: FDRs of 1196 Danish CRC patients
      diagnosed between 1995 and 1998 (baseline) were identified and the family history
      of cancer was assessed at baseline using Danish medical registries; 4182 FDRs
      without CRC from 1060 of the families were matched on age and gender with ten
      individuals from the general population and followed from baseline to 2010.
      Family history was updated with any new cancer event during follow-up. RESULTS:
      Using Cox proportional hazard modeling the risk estimates were: at least one
      relative with CRC: hazard ratio (HR)=1.78 (95%CI: 1.45, 2.17), one relative with
      CRC diagnosed after the age of 50: HR=1.68 (95%CI: 1.32, 2.14), one relative with
      CRC diagnosed before the age of 50: HR=1.86 (95%CI: 0.70, 4.94), and multiple
      affected relatives: HR=2.04 (95%CI: 1.38, 3.00). CONCLUSION: Although the overall
      risk in FDRs of CRC patients in our study was comparable with the results of
      previous studies, the risk in families with multiple relatives with CRC or one
      CRC patient diagnosed young may be lower than reported previously.

PMID- 26223562
TI  - Tenancy and African American Marriage in the Postbellum South.
AB  - The pervasiveness of tenancy in the postbellum South had countervailing effects
      on marriage between African Americans. Tenancy placed severe constraints on
      African American women's ability to find independent agricultural work.
      Freedwomen confronted not only planters' reluctance to contract directly with
      women but also whites' refusal to sell land to African Americans. Marriage
      consequently became one of African American women's few viable routes into the
      agricultural labor market. We find that the more counties relied on tenant
      farming, the more common was marriage among their youngest and oldest African
      American residents. However, many freedwomen resented their subordinate status
      within tenant marriages. Thus, we find that tenancy contributed to union
      dissolution as well as union formation among freedpeople. Microdata tracing
      individuals' marital transitions are consistent with these county-level results. 

PMID- 26223563
TI  - Predicting and managing heat dissipation from a neural probe.
AB  - Light stimulating neural probes are rapidly increasing our understanding of
      neural pathways. Relocating the externally coupled light source to the probe tip
      has the potential to dramatically improve the flexibility of the technique.
      However, this approach would generate heat within the embedded probe where even
      minor temperature excursions could easily damage tissues under study. A COMSOL
      model was used to study the thermal effects of these heated probes in the brain
      including blood perfusion and metabolic heating, and to investigate the effect of
      passive methods for improving heat dissipation. The probe temperature initially
      decreases with insertion depth, and then becomes steady. Extending the probe
      beyond the heated region has a similar effect, while increasing the size of the
      heated region steadily decreases the probe temperature. Increasing the thermal
      conductivity of the probe promotes spreading, decreasing the probe temperature.
      The effects of insertion depth and probe power dissipation were experimentally
      tested with a microfabricated, heated mock neural probe. The heated probe was
      tested in 0.65 % agarose gel at room temperature and in ex vivo cow brain at body
      temperature. The thermal resistance between the probe and the neural tissue or
      agarose gel was determined at a range of insertion depths and compared to the
      COMSOL model.

PMID- 26223565
TI  - Effect of number of motor units and muscle fibre type on surface electromyogram.
AB  - Reduction in number of motor units (nMU) and fast fibre ratio (FFR) is associated
      with disease or atrophy when this is rapid. There is a need to study the effect
      of nMU and FFR to analyse the association with ageing and disease. This study has
      developed a mathematical model to investigate the relationship between nMU and
      FFR on surface electromyogram (sEMG) of the biceps muscles. The model has been
      validated by comparing the simulation outcomes with experiments comparing the
      sEMG of physically active younger and older cohort. The results show that there
      is statistically significant difference between the two groups, and the
      simulation studies closely model the experimental results. This model can be
      applied to identify the cause of muscle weakness among the elderly due to factors
      such as muscle dystrophy or preferential loss of type F muscle fibres. 

PMID- 26223568
TI  - Morphine Synovial Fluid Concentrations After Intravenous Regional Limb Perfusion
      in Standing Horses.
AB  - OBJECTIVE: To determine synovial concentrations of morphine after intravenous
      regional limb perfusion (IVRLP) with morphine or morphine in combination with
      gentamicin in clinically healthy, standing sedated horses. STUDY DESIGN:
      Experimental. ANIMALS: Adult horses (n = 6). METHODS: IVRLP was performed using
      0.1 mg/kg morphine (M) in standing sedated horses. After a 3-week washout period,
      IVRLP was performed on the same forelimb with a combination of 0.1 mg/kg morphine
      and 1 g gentamicin (M/G). Synovial fluid from the middle carpal joint of the
      perfused limb and jugular blood samples were collected immediately before each
      perfusion and 20 minutes, and 2, 8, and 24 hours after IVRLP. Morphine and
      gentamicin concentrations were determined by ELISA. Data were assessed using 2
      way repeated measures ANOVA with significance set at P <= .05. RESULTS: Synovial
      fluid morphine concentrations were greatest 20 minutes after perfusion. Mean +/-
      SD peak synovial morphine concentrations over 12 perfusions were 3903 +/- 4881
      ng/mL. There was no significant difference in morphine synovial concentrations
      after M or M/G. Plasma morphine concentrations peaked within 2 hours of perfusion
      (range, 11-63 ng/mL). Mean peak gentamicin concentrations in synovial fluid were
      76,315 +/- 39,809 ng/mL. IVRLP morphine did not cause clinically apparent adverse
      effects. CONCLUSIONS: IVRLP in standing sedated horses results in measurable
      levels of morphine in synovial fluid and synovial concentrations of gentamicin
      after perfusion in combination with morphine are equivalent to those previously
      reported.

PMID- 26223569
TI  - Assessment of Intrathecal Pressure in Chondrodystrophic Dogs With Acute
      Thoracolumbar Disk Disease.
AB  - OBJECTIVES: To assess intrathecal pressure (ITP) in chondrodystrophic dogs with
      thoracolumbar disk extrusion. STUDY DESIGN: Prospective cohort study. ANIMALS:
      Group 1: 11 chondrodystrophic dogs with thoracolumbar disk extrusion and present
      deep pain sensation. Group 2 (control): 3 healthy chondrodystrophic laboratory
      dogs without spinal disease. METHODS: Diagnosis was based on neurologic signs,
      magnetic resonance imaging (MRI) findings, and surgical confirmation. Blood
      pressure was maintained within physiologic range during anesthesia. A
      standardized surgical procedure was applied to minimize factors that could
      influence measurement readings. An extended hemilaminectomy was performed and ITP
      was measured with a fiber optic catheter. The catheter was inserted in the
      subarachnoid space 1 spinal segment caudal to the level of herniation and its tip
      was advanced to the site of compression. RESULTS: Significantly higher ITP
      occurred in chondrodystrophic dogs with acute thoracolumbar disk disease compared
      with controls. ITP was not associated with duration of clinical signs, neurologic
      status, outcome, degree of spinal cord compression, or signal intensity changes
      as assessed by MRI. CONCLUSION: Acute thoracolumbar disk disease leads to
      elevated ITP in chondrodystrophic dogs, which may contribute to increased
      compression of spinal cord parenchyma.

PMID- 26223570
TI  - Myostatin inhibitors in sports drug testing: Detection of myostatin-neutralizing
      antibodies in plasma/serum by affinity purification and Western blotting.
AB  - PURPOSE: Myostatin is a key regulator of skeletal muscle growth and inhibition of
      its signaling pathway results in an increased muscle mass and function. The aim
      of this study was to develop a qualitative detection assay for myostatin
      neutralizing antibodies for doping control purposes by using immunological
      approaches. EXPERIMENTAL DESIGN: To detect different types of myostatin
      neutralizing antibodies irrespective of their amino acid sequence, an
      immunological assay specific for antibodies directed against myostatin and having
      a human Fc domain was established. Affinity purification and Western blotting
      strategies were combined to allow extracting and identifying relevant analytes
      from 200 MUL of plasma/serum in a non-targeted approach. The assay was
      characterized regarding specificity, linearity, precision, robustness, and
      recovery. RESULTS: The assay was found to be highly specific, robust, and linear
      from 0.1 to 1 MUg/mL. The precision was successfully specified at three different
      concentrations and the recovery of the affinity purification was 58%. CONCLUSIONS
      AND CLINICAL RELEVANCE: Within this study, an immunological detection assay for
      myostatin-neutralizing antibodies present in plasma/serum specimens was developed
      and successfully characterized. The presented approach can easily be modified to
      include other therapeutic antibodies and serves as proof-of-concept for the
      detection of antibody-based myostatin inhibitors in doping control samples.

PMID- 26223571
TI  - Diagnosis and treatment of bronchopulmonary neuroendocrine tumours: State of the
      art.
AB  - Bronchopulmonary neuroendocrine tumours (BP-NET) are a heterogeneous population
      of neoplasms with different pathology, clinical behaviour and prognosis compared
      to the more common lung cancers. The management of BP-NET patients is largely
      based on studies with a low level of evidence and extrapolation of data obtained
      from more common types of neuroendocrine tumours. This review reflects our view
      of the current state of the art of diagnosis and treatment of patients with BP
      NET. 

PMID- 26223572
TI  - Size-selective yolk-shell nanoreactors with nanometer-thin porous polymer shells.
AB  - Yolk-shell nanoreactors with metal nanoparticle core and ultrathin porous polymer
      shells are effective catalysts for heterogeneous reactions. Polymer shells
      provide size-selectivity and improved reusability of catalyst. Nanocapsules with
      single-nanometer porous shells are prepared by vesicle-templated directed
      assembly. Metal nanoparticles are formed either by selective initiation in pre
      fabricated nanocapsules or simultaneously with the creation of a crosslinked
      polymer shell. In this study, we investigated the oxidation of benzyl alcohol and
      benzaldehyde catalyzed by gold nanoparticles and hydrogenation of cyclohexene
      catalyzed by platinum nanoparticles. Comparison of newly created nanoreactors
      with commercially available nanoparticles revealed superior reusability and size
      selectivity in nanoreactors while showing no negative effect on reaction
      kinetics. 

PMID- 26223573
TI  - Biological processes and pathway changes in isoflurane-induced anesthesia
      revealed by bioinformatics analysis of gene expression profiles.
AB  - OBJECTIVE: To identify differentially expressed genes (DEGs) and further analyze
      potential biological processes and pathways involved in isoflurane-induced
      anesthesia. METHODS: Microarray data (ID: GSE64617) from rat brains treated with
      exposure to either isoflurane in oxygen (2%) (test group) or oxygen alone
      (control group) for 15 min were downloaded from Gene Expression Omnibus. Data pre
      processing was performed using the Affy package, followed by DEG screening using
      the limma package. Protein-protein interactions (PPIs) among DEGs were obtained
      from STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), and
      then visualized by constructing a network using Cytoscape. Functional and pathway
      enrichment analyses were further implemented to identify the biological processes
      and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways enriched by DEGs.
      RESULTS: A total of 240 DEGs were identified between the test and control groups,
      including 128 up-regulated DEGs and 112 down-regulated DEGs in the test group, of
      which 17 DEGs with a connectivity degree >4 were identified as hub genes (e.g.,
      Pik3r1 and Pik3r2) in the constructed PPI network. Additionally, Slc17a7 and
      Camk4 interacted with Syn1, and Pik3r1 interacted with Pik3r2. Enrichment
      analysis further revealed the significantly enriched biological processes of
      'synaptic transmission', 'cell-cell signaling' and 'transmission of nerve
      impulse' (e.g., Slc17a7, Camk4, Syn1, Gria1, Prkcg and Lphn1), as well as KEGG
      pathways including 'focal adhesion', 'Fc gamma R-mediated phagocytosis' (e.g.,
      Prkcg, Pik3r1 and Pik3r2), and 'regulation of actin cytoskeleton' (e.g., Pik3r1
      and Pik3r2). CONCLUSIONS: The identified DEGs significantly enriched in
      biological processes and KEGG pathways might be implicated in isoflurane-induced
      anesthesia.

PMID- 26223574
TI  - Continuous rocuronium administration for tracheomalacia.

PMID- 26223575
TI  - Regio- and Enantioselective Aza-Diels-Alder Reactions of 3-Vinylindoles: A
      Concise Synthesis of the Antimalarial Spiroindolone NITD609.
AB  - An asymmetric aza-Diels-Alder reaction of 3-vinylindoles with isatin-derived
      ketimines has been developed. A series of spiroindolone derivatives were thus
      obtained in good to excellent yields with excellent enantioselectivity (up to 96
      % yield and 99 % ee). Furthermore, the antimalarial compound NITD609 could be
      obtained in three steps with an overall yield of 40.6 %. Control experiments and
      operando IR experiments imply a concerted reaction pathway. The regioselectivity
      and exo selectivity result from pi-pi interactions between the two indoline rings
      of the two reactants.

PMID- 26223576
TI  - Role of microRNAs Located on Chromosome Arm 10q in Malignant Gliomas.
AB  - Deletions of chromosome arm 10q are found in most glioblastomas and subsets of
      lower grade gliomas. Mutations in the PTEN gene at 10q23.3 are restricted to less
      than half of the 10q-deleted gliomas, suggesting additional glioma-associated
      tumor suppressors on 10q. We investigated 64 astrocytic gliomas of different
      malignancy grades for aberrant expression of 16 microRNAs (miRNAs) on 10q.
      Thereby, we identified four miRNAs (miR-107, miR-146b-5p, miR-346, miR-1287-5p)
      whose expression was frequently down-regulated in anaplastic astrocytomas and/or
      glioblastomas. DNA methylation analyses revealed 5'-CpG site hypermethylation of
      miR-346 in more than two-thirds of primary glioblastomas, while aberrant 5'-CpG
      site methylation of miR-146b-5p was frequent in IDH1-mutant astrocytomas and
      secondary glioblastomas. Overexpression of either of the four miRNAs in glioma
      cell lines reduced cell proliferation and/or increased caspase-3/7 activity.
      Expression analyses of miRNA overexpressing glioma cells and 3'-untranslated
      region luciferase reporter gene assays revealed evidence that these miRNAs post
      transcriptionally regulate expression of glioma-relevant genes, including CDK6
      (miR-107), EGFR (miR-146b-5p, miR-1287-5p), TERT and SEMA6A (miR-346), all of
      which are overexpressed in malignant gliomas in situ. In summary, we show that
      the 10q-located miRNAs miR-107, miR-146b-5p, miR-346 and miR-1287-5p are
      frequently down-regulated in malignant gliomas and thereby may support
      overexpression of important glioma growth-promoting genes.

PMID- 26223577
TI  - Effect of re-transfusion systems on physiotherapy participation and transfusion
      in total knee joint arthroplasty.
AB  - BACKGROUND: Total knee joint arthroplasty is associated with significant blood
      loss. We hypothesized that re-transfusion drains would be associated with a
      lesser requirement for allogeneic blood transfusion and result in earlier
      physiotherapy participation and decreased length of hospital stay. METHODS: We
      performed a retrospective analysis of 303 patients with a mean age of 68.3 years
      (44-91) who underwent unilateral primary total knee joint arthroplasty within a
      single orthopaedic unit. A re-transfusion drain, deep drain, superficial drain or
      no drain was placed at the time of surgery. Blood tests were taken pre- and post
      operatively, and blood transfusions were given based on the haemoglobin and
      clinical symptoms. Medical records data were used to determine the day patients
      sat out of bed, mobilized more than 10 m and were discharged from hospital.
      RESULTS: Patients with a re-transfusion drain were able to sit out of bed (P =
      0.006), mobilize more than 10 m (P = 0.006) and were ready for discharge earlier
      (P = 0.013) than those without a re-transfusion drain. The use of a re
      transfusion drain showed no effect on allogenic blood transfusion requirement;
      however, it was associated with decreased haemoglobin drop when compared with
      other drain types (P = 0.003). CONCLUSION: Our results suggest that the use of a
      re-transfusion system following total knee arthroplasty has beneficial
      physiotherapy outcomes and a decreased length of stay.

PMID- 26223578
TI  - Grip forces during fast point-to-point and continuous hand movements.
AB  - Three experiments investigated the grip force exerted by the fingers on an object
      displaced actively in the near-body space. In one condition (unimanual) the
      object was held by one hand with the tripod grip and was moved briskly back and
      forth along one of the three coordinate directions (up-down, left-right, near
      far). In the second condition (bimanual) the same point-to-point movements were
      performed while holding the object with the index and middle fingers of both
      hands. In the third condition (bimanual) the object was held as in the second
      condition and moved along a circular path lying in one of the three coordinate
      planes (horizontal, frontal, sagittal). In all conditions participants were asked
      to exert a baseline level of grip force largely exceeding the safety margin
      against slippage. Both grip forces and hand displacements were measured with high
      accuracy. As reported in previous studies, in the two point-to-point conditions
      we observed an upsurge of the grip force at the onset and at the end the
      movements. However, the timing of the transient increases of the grip force
      relative to hand kinematics did not confirm the hypothesis set forth by several
      previous studies that grip modulation is a pre-planned action based on an
      internal model of the expected effects of the movement. In the third condition,
      the systematic modulation of the grip force also for circular movements was again
      at variance with the internal model hypothesis because it cannot be construed as
      a pre-planned action aiming at countering large changes in dynamic load. We argue
      that a parsimonious account of the covariations of load and grip forces can be
      offered by taking into account the visco-elastic properties of the neuromuscular
      system. 

PMID- 26223580
TI  - Validation and utility of the Attitudes to Ageing Questionnaire: Links to
      menopause and well-being trajectories.
AB  - OBJECTIVES: Qualitative studies show that women link menopause to the ageing
      process, and yet surprisingly little research has investigated how attitudes to
      ageing might shape women's experience of menopause, as well as their overall well
      being at midlife. This study validated the Attitudes to Ageing Questionnaire
      (AAQ) for use among midlife women, and explored the AAQ's role in predicting
      menopausal factors and 10 year well-being trajectories in the midlife group.
      STUDY DESIGN: Scale validation involved cross-sectional group comparisons of the
      AAQ factor structure between a sample of midlife women aged 40-60 (n=517) and
      sample of women aged over 60 (n=259). Longitudinal data on 10-year change in
      subjective well-being was analysed for a subsample of the midlife group (n=492).
      MAIN OUTCOME MEASURES: Hot flush interference ratings, menopausal beliefs,
      subjective well-being. RESULTS: Assessment of measurement invariance showed
      support for configural and scalar invariance, with partial support for strict
      invariance. Midlife women exhibited more negative attitudes to ageing on the
      psychosocial loss subscale compared to older women. Attitude to psychosocial loss
      was the strongest predictor of women's experience of menopause, and women with a
      negative attitude to psychosocial loss did not experience gains in subjective
      well-being with age that were characteristic of those with a positive attitude.
      CONCLUSIONS: Findings demonstrate the validity and utility of the AAQ for use
      among midlife women. Policies to enhance attitudes to ageing could be beneficial
      to protect well-being during the second half of life.

PMID- 26223581
TI  - Urinary isoflavone and lignan phytoestrogen levels and risk of uterine fibroid in
      Jamaican women.
AB  - BACKGROUND: Isoflavones and lignans are phytoestrogens, and therefore, are able
      to bind to and activate estrogen receptors. The resultant estrogenic or
      antiestrogenic effect is dependent on the concentration of these phytoestrogens
      relative to endogenous estrogens and the site of their action, among others.
      Thus, isoflavones and lignans act as selective estrogen receptor modulators;
      having a beneficial effect in some tissues while simultaneously causing
      deleterious changes in others. OBJECTIVE: This case-control study investigates
      the relationship between urinary concentrations of genistein, daidzein, equol,
      and enterolactone, and the presence of uterine leiomyomas (fibroids) in Jamaican
      women. DESIGN: Phytoestrogen concentration in spot urine samples from 157 uterine
      fibroid cases and 171 fibroid-free controls diagnosed by ultrasonography, were
      assessed by Time-resolved Fluoroimmnoassay. Statistical evaluations were
      performed using SPSS 12.0. RESULTS: The median concentration of urinary
      enterolactone was significantly different between uterine fibroid cases and
      controls (p=0.029). However, this was not observed to affect risk of uterine
      fibroid, as trends across quartiles of urine enterolactone did not differ
      significantly between cases and controls. Median urinary genistein (p=0.510),
      daidzein (p=0.838), equol (p=0.621), total isoflavones (0.510) and total
      phytoestrogens (p=0.084) were similar for both groups. Binary logistic regression
      analysis of quartiles of urine genistein, daidzein, equol, enterolactone, total
      isoflavones, and total phytoestrogens showed no association with uterine fibroid.
      CONCLUSIONS: Uterine fibroid cases had a higher median urine concentration of
      enterolactone compared with controls. However, this was not observed to affect
      ones risk of fibroid. Neither was urine genistein, daidzein, equol total
      isoflavones, and total phytoestrogens observed to be associated with risk of
      uterine fibroid.

PMID- 26223579
TI  - Self-motion direction discrimination in the visually impaired.
AB  - Despite the close interrelation between vestibular and visual processing (e.g.,
      vestibulo-ocular reflex), surprisingly little is known about vestibular function
      in visually impaired people. In this study, we investigated thresholds of passive
      whole-body motion discrimination (leftward vs. rightward) in nine visually
      impaired participants and nine age-matched sighted controls. Participants were
      rotated in yaw, tilted in roll, and translated along the interaural axis at two
      different frequencies (0.33 and 2 Hz) by means of a motion platform. Superior
      performance of visually impaired participants was found in the 0.33 Hz roll tilt
      condition. No differences were observed in the other motion conditions. Roll
      tilts stimulate the semicircular canals and otoliths simultaneously. The results
      could thus reflect a specific improvement in canal-otolith integration in the
      visually impaired and are consistent with the compensatory hypothesis, which
      implies that the visually impaired are able to compensate the absence of visual
      input. 

PMID- 26223582
TI  - Small molecule and RNAi induced phenotype transition of expanded and primary
      colonic epithelial cells.
AB  - Recent progress in mammalian intestinal epithelial cell culture led to novel
      concepts of tissue modeling. Especially the development of phenotypically stable
      cell lines from individual animals enables an investigation of distinct
      intestinal loci and disease states. We here report primary and prolonged culture
      of normal porcine epithelial cells from colon for cell line development. In
      addition, a novel primary three-dimensional intestinal culture system is
      presented, which generated organoids composed of a highly polarized epithelial
      layer lining a core of subepithelial tissue. Cellular characterization of
      monolayer cell lines revealed epithelial identity and pointed to a proliferative
      crypt cell phenotype. We evaluated both RNAi and chemical approaches to induce
      epithelial differentiation in generated cell lines by targeting promoters of
      epithelial to mesenchymal transition (EMT). By in silico prediction and ectopic
      expression, miR-147b was proven to be a potent trigger of intestinal epithelial
      cell differentiation. Our results outline an approach to generate phenotypically
      stable cell lines expanded from primary colonic epithelial cultures and
      demonstrate the relevance of miR-147b and chemical inhibitors for promoting
      epithelial differentiation features. 

PMID- 26223583
TI  - Solid waste forecasting using modified ANFIS modeling.
AB  - Solid waste prediction is crucial for sustainable solid waste management.
      Usually, accurate waste generation record is challenge in developing countries
      which complicates the modelling process. Solid waste generation is related to
      demographic, economic, and social factors. However, these factors are highly
      varied due to population and economy growths. The objective of this research is
      to determine the most influencing demographic and economic factors that affect
      solid waste generation using systematic approach, and then develop a model to
      forecast solid waste generation using a modified Adaptive Neural Inference System
      (MANFIS). The model evaluation was performed using Root Mean Square Error (RMSE),
      Mean Absolute Error (MAE) and the coefficient of determination (R2). The results
      show that the best input variables are people age groups 0-14, 15-64, and people
      above 65 years, and the best model structure is 3 triangular fuzzy membership
      functions and 27 fuzzy rules. The model has been validated using testing data and
      the resulted training RMSE, MAE and R2 were 0.2678, 0.045 and 0.99, respectively,
      while for testing phase RMSE =3.986, MAE = 0.673 and R2 = 0.98. IMPLICATIONS: To
      date, a few attempts have been made to predict the annual solid waste generation
      in developing countries. This paper presents modeling of annual solid waste
      generation using Modified ANFIS, it is a systematic approach to search for the
      most influencing factors and then modify the ANFIS structure to simplify the
      model. The proposed method can be used to forecast the waste generation in such
      developing countries where accurate reliable data is not always available.
      Moreover, annual solid waste prediction is essential for sustainable planning.

PMID- 26223584
TI  - Optimizing the pre-referral workup for gastroenterology and hepatology specialty
      care: consensus using the Delphi method.
AB  - RATIONALE, AIMS AND OBJECTIVES: Specialty care referrals have doubled in the last
      decade. Optimization of the pre-referral workup by a primary care doctor can lead
      to a more efficient first specialty visit with the patient. Guidance regarding
      pre-referral laboratory testing is a first step towards improving the specialty
      referral process. Our aim was to establish consensus regarding appropriate pre
      referral workup for common gastrointestinal and liver conditions. METHODS: The
      Delphi method was used to establish local consensus for recommending certain
      laboratory tests prior to specialty referral for 13 clinical conditions. Seven
      conditions from The University of Michigan outpatient referral guidelines were
      used as a baseline. An expert panel of three PCPs and nine gastroenterologists
      from three academic hospitals participated in three iterative rounds of
      electronic surveys. Each panellist ranked each test using a 5-point Likert scale
      (strongly disagree to strongly agree). Local panellists could recommend
      additional tests for the initial diagnoses, and also recommended additional
      diagnoses needing guidelines: iron deficiency anaemia, abdominal pain, irritable
      bowel syndrome, fatty liver disease, liver mass and cirrhosis. Consensus was
      defined as >=70% of experts scoring >=4 (agree or strongly agree). RESULTS:
      Applying Delphi methodology to extrapolate externally developed referral
      guidelines for local implementation resulted in considerable modifications. For
      some conditions, many tests from the external group were eliminated by the local
      group (abdominal bloating; iron deficiency anaemia; irritable bowel syndrome). In
      contrast, for chronic diarrhoea, abnormal liver enzymes and viral hepatitis,
      all/most original tests were retained with additional tests added. For liver
      mass, fatty liver disease and cirrhosis, there was high concordance among the
      panel with few tests added or eliminated. CONCLUSIONS: Consideration of
      externally developed referral guidelines using a consensus-building process leads
      to significant local tailoring and adaption. Our next steps include
      implementation and dissemination of these guidelines and evaluating their impact
      on care efficiency in clinical practice.

PMID- 26223585
TI  - Molecular cloning and characterization of two YGL039w genes encoding broad
      specificity NADPH-dependent aldehyde reductases from Kluyveromyces marxianus
      strain DMB1.
AB  - Two genes from Kluyveromyces marxianus strain DMB1, YGL039w1 and YGL039w2, encode
      putative uncharacterized oxidoreductases that respectively share 42 and 44%
      identity with the Saccharomyces cerevisiae S288c NADPH-dependent methylglyoxal
      reductase (EC 1.1.1.283). To determine the enzymatic characteristics of their
      products, the two genes were expressed in recombinant Escherichia coli cells,
      after which the YGL039w1 and YGL039w2 proteins were purified to homogeneity. In
      the presence of NADPH, both enzymes showed reductive activities toward at least
      nine aldehyde substrates, but no NADP(+)-dependent oxidative activities. These
      two YGL039w proteins thus appear to be aldehyde reductases. In addition, although
      both enzymes retained more than 70% of their activities after incubation for 30
      min at temperatures below 40 degrees C or at pHs between 5.5 and 11.3, YGL039w2
      was slightly more thermostable than YGL039w1. 

PMID- 26223586
TI  - Bringing guest scientists to the university biology classroom via the web.
AB  - This commentary describes an initiative to bring national and international guest
      scientists to undergraduate and introductory graduate classrooms via web
      videoconferencing to facilitate interesting and effective research-informed
      teaching. Interactions center around both journal articles authored by the guests
      that are in line with weekly course lecture topics and on learning about the
      nature of academia in other parts of the world. Some particularly interesting
      perspectives from guests have come about by connecting with a journal editor-in
      chief, a textbook author and with a scientist who shared a recently rejected
      manuscript and peer reviews. Beyond allowing students a unique behind-the-scenes
      look into how research questions are asked and answered, this initiative helps
      overcome the limited nature of a single instructor's research area to better
      complement the comprehensive scope of university courses. 

PMID- 26223587
TI  - Absence of a gene encoding cytosine deaminase in the genome of the agaricomycete
      Coprinopsis cinerea enables simple marker recycling through 5-fluorocytosine
      counterselection.
AB  - Coprinopsis cinerea is a model species for molecular genetics studies of sexual
      development in agaricomycetes or homobasidiomycetes. Recently, efficient gene
      targeting was established in this fungus by generating Cc.ku70 or Cc.lig4
      disruptants. To determine the molecular mechanisms underlying sexual development,
      which involves many genes, generating multiple gene disruptants is required.
      However, the number of transformation markers available for C. cinerea is
      limited. This problem would be solved by establishing marker recycling. In this
      study, we found that C. cinerea lacks a gene encoding a homolog of Saccharomyces
      cerevisiae cytosine deaminase (Fcy1p) in its genome, which is present in many
      other fungi. We also observed that C. cinerea is resistant to 5-fluorocytosine.
      Based on these findings, we established a simple marker recycling method in this
      fungus using 5-fluorocytosine counterselection after heterologous expression of
      FCY1 derived from Pleurotus ostreatus, together with the hygromycin resistance
      gene. This study proposes a simple genetic manipulation system that can be
      performed using wild-type strains of several fungi that lack a gene homologous to
      S. cerevisiae FCY1 in their genomes. 

PMID- 26223588
TI  - Secret service.

PMID- 26223589
TI  - Realistic risks.

PMID- 26223590
TI  - Faith and science can find common ground.

PMID- 26223602
TI  - Antibody drugs for Alzheimer's show glimmers of promise.

PMID- 26223604
TI  - NASA spies Earth-sized exoplanet orbiting Sun-like star.

PMID- 26223603
TI  - NASA launches mission to Greenland.

PMID- 26223605
TI  - Neanderthals had outsize effect on human biology.

PMID- 26223607
TI  - 'Half-pipe' telescope will probe dark energy in teen Universe.

PMID- 26223606
TI  - Budget showdown leaves US science agencies in limbo.

PMID- 26223609
TI  - Hospital checklists are meant to save lives - so why do they often fail?

PMID- 26223610
TI  - The boom in mini stomachs, brains, breasts, kidneys and more.

PMID- 26223611
TI  - History: From blackboards to bombs.

PMID- 26223612
TI  - Policy: Define biomass sustainability.

PMID- 26223614
TI  - World Heritage Site: Many ways to access hominin fossil finds.

PMID- 26223615
TI  - Europe: Universities aim for a sustainable future.

PMID- 26223616
TI  - Education: Initiatives to bridge faith and science.

PMID- 26223617
TI  - Forests: Tree rings track climate trade-offs.

PMID- 26223618
TI  - Irwin Allan Rose (1926-2015).

PMID- 26223619
TI  - Inorganic chemistry: Movies of a growth mechanism.

PMID- 26223620
TI  - Materials science: Composite for energy storage takes the heat.

PMID- 26223621
TI  - Strong-field physics: Harmonic radiation from crystals.

PMID- 26223622
TI  - Correction.

PMID- 26223623
TI  - Magnetospherically driven optical and radio aurorae at the end of the stellar
      main sequence.
AB  - Aurorae are detected from all the magnetized planets in our Solar System,
      including Earth. They are powered by magnetospheric current systems that lead to
      the precipitation of energetic electrons into the high-latitude regions of the
      upper atmosphere. In the case of the gas-giant planets, these aurorae include
      highly polarized radio emission at kilohertz and megahertz frequencies produced
      by the precipitating electrons, as well as continuum and line emission in the
      infrared, optical, ultraviolet and X-ray parts of the spectrum, associated with
      the collisional excitation and heating of the hydrogen-dominated atmosphere. Here
      we report simultaneous radio and optical spectroscopic observations of an object
      at the end of the stellar main sequence, located right at the boundary between
      stars and brown dwarfs, from which we have detected radio and optical auroral
      emissions both powered by magnetospheric currents. Whereas the magnetic activity
      of stars like our Sun is powered by processes that occur in their lower
      atmospheres, these aurorae are powered by processes originating much further out
      in the magnetosphere of the dwarf star that couple energy into the lower
      atmosphere. The dissipated power is at least four orders of magnitude larger than
      what is produced in the Jovian magnetosphere, revealing aurorae to be a
      potentially ubiquitous signature of large-scale magnetospheres that can scale to
      luminosities far greater than those observed in our Solar System. These
      magnetospheric current systems may also play a part in powering some of the
      weather phenomena reported on brown dwarfs. 

PMID- 26223624
TI  - Real-time observation of interfering crystal electrons in high-harmonic
      generation.
AB  - Acceleration and collision of particles has been a key strategy for exploring the
      texture of matter. Strong light waves can control and recollide electronic
      wavepackets, generating high-harmonic radiation that encodes the structure and
      dynamics of atoms and molecules and lays the foundations of attosecond science.
      The recent discovery of high-harmonic generation in bulk solids combines the idea
      of ultrafast acceleration with complex condensed matter systems, and provides
      hope for compact solid-state attosecond sources and electronics at optical
      frequencies. Yet the underlying quantum motion has not so far been observable in
      real time. Here we study high-harmonic generation in a bulk solid directly in the
      time domain, and reveal a new kind of strong-field excitation in the crystal.
      Unlike established atomic sources, our solid emits high-harmonic radiation as a
      sequence of subcycle bursts that coincide temporally with the field crests of one
      polarity of the driving terahertz waveform. We show that these features are
      characteristic of a non-perturbative quantum interference process that involves
      electrons from multiple valence bands. These results identify key mechanisms for
      future solid-state attosecond sources and next-generation light-wave electronics.
      The new quantum interference process justifies the hope for all-optical band
      structure reconstruction and lays the foundation for possible quantum logic
      operations at optical clock rates. 

PMID- 26223625
TI  - Flexible high-temperature dielectric materials from polymer nanocomposites.
AB  - Dielectric materials, which store energy electrostatically, are ubiquitous in
      advanced electronics and electric power systems. Compared to their ceramic
      counterparts, polymer dielectrics have higher breakdown strengths and greater
      reliability, are scalable, lightweight and can be shaped into intricate
      configurations, and are therefore an ideal choice for many power electronics,
      power conditioning, and pulsed power applications. However, polymer dielectrics
      are limited to relatively low working temperatures, and thus fail to meet the
      rising demand for electricity under the extreme conditions present in
      applications such as hybrid and electric vehicles, aerospace power electronics,
      and underground oil and gas exploration. Here we describe crosslinked polymer
      nanocomposites that contain boron nitride nanosheets, the dielectric properties
      of which are stable over a broad temperature and frequency range. The
      nanocomposites have outstanding high-voltage capacitive energy storage
      capabilities at record temperatures (a Weibull breakdown strength of 403
      megavolts per metre and a discharged energy density of 1.8 joules per cubic
      centimetre at 250 degrees Celsius). Their electrical conduction is several orders
      of magnitude lower than that of existing polymers and their high operating
      temperatures are attributed to greatly improved thermal conductivity, owing to
      the presence of the boron nitride nanosheets, which improve heat dissipation
      compared to pristine polymers (which are inherently susceptible to thermal
      runaway). Moreover, the polymer nanocomposites are lightweight, photopatternable
      and mechanically flexible, and have been demonstrated to preserve excellent
      dielectric and capacitive performance after intensive bending cycles. These
      findings enable broader applications of organic materials in high-temperature
      electronics and energy storage devices.

PMID- 26223626
TI  - Onset of Antarctic Circumpolar Current 30 million years ago as Tasmanian Gateway
      aligned with westerlies.
AB  - Earth's mightiest ocean current, the Antarctic Circumpolar Current (ACC),
      regulates the exchange of heat and carbon between the ocean and the atmosphere,
      and influences vertical ocean structure, deep-water production and the global
      distribution of nutrients and chemical tracers. The eastward-flowing ACC occupies
      a unique circumglobal pathway in the Southern Ocean that was enabled by the
      tectonic opening of key oceanic gateways during the break-up of Gondwana (for
      example, by the opening of the Tasmanian Gateway, which connects the Indian and
      Pacific oceans). Although the ACC is a key component of Earth's present and past
      climate system, the timing of the appearance of diagnostic features of the ACC
      (for example, low zonal gradients in water-mass tracer fields) is poorly known
      and represents a fundamental gap in our understanding of Earth history. Here we
      show, using geophysically determined positions of continent-ocean boundaries,
      that the deep Tasmanian Gateway opened 33.5 +/- 1.5 million years ago (the errors
      indicate uncertainty in the boundary positions). Following this opening,
      sediments from Indian and Pacific cores recorded Pacific-type neodymium isotope
      ratios, revealing deep westward flow equivalent to the present-day Antarctic
      Slope Current. We observe onset of the ACC at around 30 million years ago, when
      Southern Ocean neodymium isotopes record a permanent shift to modern Indian
      Atlantic ratios. Our reconstructions of ocean circulation show that massive
      reorganization and homogenization of Southern Ocean water masses coincided with
      migration of the northern margin of the Tasmanian Gateway into the mid-latitude
      westerly wind band, which we reconstruct at 64 degrees  S, near to the northern
      margin. Onset of the ACC about 30 million years ago coincided with major changes
      in global ocean circulation and probably contributed to the lower atmospheric
      carbon dioxide levels that appear after this time. 

PMID- 26223627
TI  - Mitochondrial reticulum for cellular energy distribution in muscle.
AB  - Intracellular energy distribution has attracted much interest and has been
      proposed to occur in skeletal muscle via metabolite-facilitated diffusion;
      however, genetic evidence suggests that facilitated diffusion is not critical for
      normal function. We hypothesized that mitochondrial structure minimizes
      metabolite diffusion distances in skeletal muscle. Here we demonstrate a
      mitochondrial reticulum providing a conductive pathway for energy distribution,
      in the form of the proton-motive force, throughout the mouse skeletal muscle
      cell. Within this reticulum, we find proteins associated with mitochondrial
      proton-motive force production preferentially in the cell periphery and proteins
      that use the proton-motive force for ATP production in the cell interior near
      contractile and transport ATPases. Furthermore, we show a rapid, coordinated
      depolarization of the membrane potential component of the proton-motive force
      throughout the cell in response to spatially controlled uncoupling of the cell
      interior. We propose that membrane potential conduction via the mitochondrial
      reticulum is the dominant pathway for skeletal muscle energy distribution. 

PMID- 26223629
TI  - Brick tunnel randomization and the momentum of the probability mass.
AB  - The allocation space of an unequal-allocation permuted block randomization can be
      quite wide. The development of unequal-allocation procedures with a narrower
      allocation space, however, is complicated by the need to preserve the
      unconditional allocation ratio at every step (the allocation ratio preserving
      (ARP) property). When the allocation paths are depicted on the K-dimensional
      unitary grid, where allocation to the l-th treatment is represented by a step
      along the l-th axis, l = 1 to K, the ARP property can be expressed in terms of
      the center of the probability mass after i allocations. Specifically, for an ARP
      allocation procedure that randomizes subjects to K treatment groups in w1 :?:wK
      ratio, w1 +?+wK =1, the coordinates of the center of the mass are (w1 i,...,wK
      i). In this paper, the momentum with respect to the center of the probability
      mass (expected imbalance in treatment assignments) is used to compare ARP
      procedures in how closely they approximate the target allocation ratio. It is
      shown that the two-arm and three-arm brick tunnel randomizations (BTR) are the
      ARP allocation procedures with the tightest allocation space among all allocation
      procedures with the same allocation ratio; the two-arm BTR is the minimum
      momentum two-arm ARP allocation procedure. Resident probabilities of two-arm and
      three-arm BTR are analytically derived from the coordinates of the center of the
      probability mass; the existence of the respective transition probabilities is
      proven. Probability of deterministic assignments with BTR is found generally
      acceptable. Copyright (c) 2015 John Wiley & Sons, Ltd. 

PMID- 26223630
TI  - Periodontal disease, tooth loss and coronary heart disease assessed by coronary
      angiography: a cross-sectional observational study.
AB  - OBJECTIVE AND BACKGROUND: To evaluate the association between periodontal
      disease, tooth loss and coronary heart disease (CHD). There is still controversy
      about the relationship between periodontal disease and tooth loss with vessel
      obstruction assessed using coronary angiography. MATERIAL AND METHODS: This cross
      sectional study included 195 patients that underwent coronary angiography and
      presented with at least six teeth. Patients were classified into three categories
      of coronary obstruction severity: absence; one or more vessels with <= 50%
      obstruction; and one or more vessels with >= 50% obstruction. The extent of
      coronary obstruction was dichotomized into 0 and >= 1 affected vessels. A
      periodontist blinded to patient CHD status conducted a full mouth examination to
      determine mean clinical attachment loss, mean periodontal probing depth and tooth
      loss. Multiple logistic regression models were applied adjusting for age, gender,
      hypertension, smoking, body mass index, low-density lipoprotein cholesterol and C
      reactive protein. RESULTS: Most patients were males (62.1%) older than 60 years
      (50.8%), and 61% of them had CHD. Mean periodontal probing depth, clinical
      attachment loss and tooth loss were 2.64 +/- 0.72 mm, 4.40 +/- 1.31 mm and 12.50
      +/- 6.98 teeth respectively. In the multivariable models, tooth loss was
      significantly associated with a higher chance of having at least one obstructed
      vessel (odds ratio = 1.04; 95% confidence interval 1.01-1.09) and with vessel
      obstruction >= 50% (odds ratio = 1.06; 95% confidence interval 1.01-1.11). No
      significant associations were found between periodontal variables and vessel
      obstruction. CONCLUSION: Tooth loss was found to be a risk indicator for CHD.

PMID- 26223631
TI  - Treating codeine dependence with buprenorphine: Dose requirements and induction
      outcomes from a retrospective case series in New South Wales, Australia.
AB  - INTRODUCTION AND AIMS: Codeine dependence is an emerging public health concern,
      yet no studies have specifically examined the treatment of codeine dependence.
      Given the lower potency of codeine it cannot be assumed that buprenorphine dose
      requirements for heroin dependence will generalise to codeine. This is the first
      study to examine buprenorphine treatment for codeine dependence. DESIGN AND
      METHODS: Retrospective case series of 19 codeine-dependent treatment entrants who
      received sublingual buprenorphine maintenance treatment through six specialist
      inpatient and outpatient treatment centres. Baseline codeine doses and
      buprenorphine dose at days 7 and 28 were collected, in addition to details on
      general demographics, pain and mental health, substance use and outcomes after 28
      days of buprenorphine treatment. RESULTS: A significant linear relationship was
      found between initial codeine dose and dose of buprenorphine given at days 7 and
      28 for the codeine dose range of 50-960 mg day-1 (mean: 564 mg; 95% confidence
      interval 431-696 mg). Median buprenorphine dose was 12.0 mg (interquartile range
      9.5 mg, range 4-32 mg) at day 7 and 16.0 mg (interquartile range 13.5 mg, range 4
      32 mg) at day 28. Buprenorphine doses received were markedly higher than
      estimated codeine doses based on standard dose conversion tables. DISCUSSION AND
      CONCLUSIONS: With increasing presentations relating to codeine dependence, these
      findings provide important guidance to clinicians. Buprenorphine doses were
      consistently higher than doses estimated based on the dose of codeine consumed,
      and were comparable with doses used in the treatment of dependence with heroin
      and more potent prescription opioids. [Nielsen S, Bruno R, Murnion B, Dunlop A,
      Degenhardt L, Demirkol A, Muhleisen P, Lintzeris N. Treating codeine dependence
      with buprenorphine: Dose requirements and induction outcomes from a retrospective
      case series in New South Wales, Australia. Drug Alcohol Rev 2015].

PMID- 26223632
TI  - Adenovirus E4-ORF3 Targets PIAS3 and Together with E1B-55K Remodels SUMO
      Interactions in the Nucleus and at Virus Genome Replication Domains.
AB  - Adenovirus E4-ORF3 and E1B-55K converge in subverting critical overlapping
      cellular pathways to facilitate virus replication. Here, we show that E1B-55K and
      E4-ORF3 induce sumoylation and the assembly of SUMO2/3 viral genome replication
      domains. Using a conjugation-deficient SUMO2 construct, we demonstrate that
      SUMO2/3 is recruited to E2A viral genome replication domains through noncovalent
      interactions. E1B-55K and E4-ORF3 have critical functions in inactivating MRN and
      ATM to facilitate viral genome replication. We show that ATM kinase inhibitors
      rescue DeltaE1B-55K/DeltaE4-ORF3 viral genome replication and that the assembly
      of E2A domains recruits SUMO2/3 independently of E1B-55K and E4-ORF3. However,
      the morphology and organization of SUMO2/3-associated E2A domains is strikingly
      different from that in wild-type Ad5-infected cells. These data reveal that E1B
      55K and E4-ORF3 specify the nuclear compartmentalization and structure of SUMO2/3
      associated E2A domains, which could have important functions in viral
      replication. We show that E4-ORF3 specifically targets and sequesters the
      cellular E3 SUMO ligase PIAS3 but not PIAS1, PIAS2, or PIAS4. The assembly of E4
      ORF3 into a multivalent nuclear matrix is required to target PIAS3. In contrast
      to MRN, PIAS3 is targeted by E4-ORF3 proteins from disparate adenovirus
      subgroups. Our studies reveal that PIAS3 is a novel and evolutionarily conserved
      target of E4-ORF3 in human adenovirus infections. Furthermore, we reveal that
      viral proteins not only disrupt but also usurp SUMO2/3 to transform the nucleus
      and assemble novel genomic domains that could facilitate pathological viral
      replication. IMPORTANCE: SUMO is a key posttranslational modification that
      modulates the function, localization, and assembly of protein complexes. In the
      ever-escalating host-pathogen arms race, viruses have evolved strategies to
      subvert sumoylation. Adenovirus is a small DNA tumor virus that is a global human
      pathogen and key biomedical agent in basic research and therapy. We show that
      adenovirus infection induces global changes in SUMO localization and conjugation.
      Using virus and SUMO mutants, we demonstrate that E1B-55K and E4-ORF3 disrupt and
      usurp SUMO2/3 interactions to transform the nucleus and assemble highly
      structured and compartmentalized viral genome domains. We reveal that the
      cellular E3 SUMO ligase PIAS3 is a novel and conserved target of E4-ORF3 proteins
      from disparate adenovirus subgroups. The induction of sumoylation and SUMO2/3
      viral replication domains by early viral proteins could play an important role in
      determining the outcome of viral infection.

PMID- 26223633
TI  - Attenuated Human Parainfluenza Virus Type 1 (HPIV1) Expressing the Fusion
      Glycoprotein of Human Respiratory Syncytial Virus (RSV) as a Bivalent HPIV1/RSV
      Vaccine.
AB  - Live attenuated recombinant human parainfluenza virus type 1 (rHPIV1) was
      investigated as a vector to express the respiratory syncytial virus (RSV) fusion
      (F) glycoprotein, to provide a bivalent vaccine against RSV and HPIV1. The RSV F
      gene was engineered to include HPIV1 transcription signals and inserted
      individually into three gene locations in each of the two attenuated rHPIV1
      backbones. Each backbone contained a single previously described attenuating
      mutation that was stabilized against deattenuation, specifically, a non
      temperature-sensitive deletion mutation involving 6 nucleotides in the
      overlapping P/C open reading frames (ORFs) (C(Delta170)) or a temperature
      sensitive missense mutation in the L ORF (L(Y942A)). The insertion sites in the
      genome were pre-N (F1), N-P (F2), or P-M (F3) and were identical for both
      backbones. In vitro, the presence of the F insert reduced the rate of virus
      replication, but the final titers were the same as the final titer of wild-type
      (wt) HPIV1. High levels of RSV F expression in cultured cells were observed with
      rHPIV1-C(Delta170)-F1, -F2, and -F3 and rHPIV1-L(Y942A)-F1. In hamsters, the
      rHPIV1-C(Delta170)-F1, -F2, and -F3 vectors were moderately restricted in the
      nasal turbinates, highly restricted in lungs, and genetically stable in vivo.
      Among the C(Delta170) vectors, the F1 virus was the most immunogenic and
      protective against wt RSV challenge. The rHPIV1-L(Y942A) vectors were highly
      restricted in vivo and were not detectably immunogenic or protective, indicative
      of overattenuation. The C(Delta170)-F1 construct appears to be suitably
      attenuated and immunogenic for further development as a bivalent intranasal
      pediatric vaccine. IMPORTANCE: There are no vaccines for the pediatric
      respiratory pathogens RSV and HPIV. We are developing live attenuated RSV and
      HPIV vaccines for use in virus-naive infants. Live attenuated RSV strains in
      particular are difficult to develop due to their poor growth and physical
      instability, but these obstacles could be avoided by the use of a vaccine vector.
      We describe the development and preclinical evaluation of live attenuated rHPIV1
      vectors expressing the RSV F protein. Two different attenuated rHPIV1 backbones
      were each engineered to express RSV F from three different gene positions. The
      rHPIV1-C(Delta170)-F1 vector, bearing an attenuating deletion mutation
      (C(Delta170)) in the P/C gene and expressing RSV F from the pre-N position, was
      attenuated, stable, and immunogenic against the RSV F protein and HPIV1 in the
      hamster model and provided substantial protection against RSV challenge. This
      study provides a candidate rHPIV1-RSV-F vaccine virus suitable for continued
      development as a bivalent vaccine against two major childhood pathogens.

PMID- 26223634
TI  - Fitness-Balanced Escape Determines Resolution of Dynamic Founder Virus Escape
      Processes in HIV-1 Infection.
AB  - To understand the interplay between host cytotoxic T-lymphocyte (CTL) responses
      and the mechanisms by which HIV-1 evades them, we studied viral evolutionary
      patterns associated with host CTL responses in six linked transmission pairs. HIV
      1 sequences corresponding to full-length p17 and p24 gag were generated by 454
      pyrosequencing for all pairs near the time of transmission, and seroconverting
      partners were followed for a median of 847 days postinfection. T-cell responses
      were screened by gamma interferon/interleukin-2 (IFN-gamma/IL-2) FluoroSpot using
      autologous peptide sets reflecting any Gag variant present in at least 5% of
      sequence reads in the individual's viral population. While we found little
      evidence for the occurrence of CTL reversions, CTL escape processes were found to
      be highly dynamic, with multiple epitope variants emerging simultaneously. We
      found a correlation between epitope entropy and the number of epitope variants
      per response (r = 0.43; P = 0.05). In cases in which multiple escape mutations
      developed within a targeted epitope, a variant with no fitness cost became fixed
      in the viral population. When multiple mutations within an epitope achieved
      fitness-balanced escape, these escape mutants were each maintained in the viral
      population. Additional mutations found to confer escape but undetected in viral
      populations incurred high fitness costs, suggesting that functional constraints
      limit the available sites tolerable to escape mutations. These results further
      our understanding of the impact of CTL escape and reversion from the founder
      virus in HIV infection and contribute to the identification of immunogenic Gag
      regions most vulnerable to a targeted T-cell attack. IMPORTANCE: Rapid
      diversification of the viral population is a hallmark of HIV-1 infection, and
      understanding the selective forces driving the emergence of viral variants can
      provide critical insight into the interplay between host immune responses and
      viral evolution. We used deep sequencing to comprehensively follow viral
      evolution over time in six linked HIV transmission pairs. We then mapped T-cell
      responses to explore if mutations arose due to adaption to the host and found
      that escape processes were often highly dynamic, with multiple mutations arising
      within targeted epitopes. When we explored the impact of these mutations on
      replicative capacity, we found that dynamic escape processes only resolve with
      the selection of mutations that conferred escape with no fitness cost to the
      virus. These results provide further understanding of the complicated viral-host
      interactions that occur during early HIV-1 infection and may help inform the
      design of future vaccine immunogens.

PMID- 26223635
TI  - An A14U Substitution in the 3' Noncoding Region of the M Segment of Viral RNA
      Supports Replication of Influenza Virus with an NS1 Deletion by Modulating
      Alternative Splicing of M Segment mRNAs.
AB  - The NS1 protein of influenza virus has multiple functions and is a determinant of
      virulence. Influenza viruses with NS1 deletions (DelNS1 influenza viruses) are a
      useful tool for studying virus replication and can serve as effective live
      attenuated vaccines, but deletion of NS1 severely diminishes virus replication,
      hampering functional studies and vaccine production. We found that WSN-DelNS1
      viruses passaged in cells consistently adapted to gain an A14U substitution in
      the 3' noncoding region of the M segment of viral RNA (vRNA) which restored
      replicative ability. DelNS1-M-A14U viruses cannot inhibit interferon expression
      in virus infected-cells, providing an essential model for studying virus
      replication in the absence of the NS1 protein. Characterization of DelNS1-M-A14U
      virus showed that the lack of NS1 has no apparent effect on expression of other
      viral proteins, with the exception of M mRNAs. Expression of the M transcripts,
      M1, M2, mRNA3, and mRNA4, is regulated by alternative splicing. The A14U
      substitution changes the splicing donor site consensus sequence of mRNA3,
      altering expression of M transcripts, with M2 expression significantly increased
      and mRNA3 markedly suppressed in DelNS1-M-A14U, but not DelNS1-M-WT, virus
      infected cells. Further analysis revealed that the A14U substitution also affects
      promoter function during replication of the viral genome. The M-A14U mutation
      increases M vRNA synthesis in DelNS1 virus infection and enhances alternative
      splicing of M2 mRNA in the absence of other viral proteins. The findings
      demonstrate that NS1 is directly involved in influenza virus replication through
      modulation of alternative splicing of M transcripts and provide strategic
      information important to construction of vaccine strains with NS1 deletions.
      IMPORTANCE: Nonstructural protein (NS1) of influenza virus has multiple
      functions. Besides its role in antagonizing host antiviral activity, NS1 is also
      believed to be involved in regulating virus replication, but mechanistic details
      are not clear. The NS1 protein is a virulence determinant which inhibits both
      innate and adaptive immunity and live attenuated viruses with NS1 deletions show
      promise as effective vaccines. However, deletion of NS1 causes severe attenuation
      of virus replication during infection, impeding functional studies and vaccine
      development. We characterized a replication-competent DelNS1 virus which carries
      an A14U substitution in the 3' noncoding region of the vRNA M segment. We found
      that M-A14U mutation supports virus replication through modulation of alternative
      splicing of mRNAs transcribed from the M segment. Our findings give insight into
      the role of NS1 in influenza virus replication and provide an approach for
      constructing replication-competent strains with NS1 deletions for use in
      functional and vaccine studies.

PMID- 26223636
TI  - Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis
      Guanylhydrazone.
AB  - Macrophages are a target for infection with HIV and represent one of the viral
      reservoirs that are relatively resistant to current antiretroviral drugs. Here we
      demonstrate that methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine analog and
      potent S-adenosylmethionine decarboxylase inhibitor, decreases HIV expression in
      monocytes and macrophages. MGBG is selectively concentrated by these cells
      through a mechanism consistent with active transport by the polyamine
      transporter. Using a macrophage-tropic reporter virus tagged with the enhanced
      green fluorescent protein, we demonstrate that MGBG decreases the frequency of
      HIV-infected cells. The effect is dose dependent and correlates with the
      production of HIV p24 in culture supernatants. This anti-HIV effect was further
      confirmed using three macrophage-tropic primary HIV isolates. Viral life cycle
      mapping studies show that MGBG inhibits HIV DNA integration into the cellular DNA
      in both monocytes and macrophages. IMPORTANCE: Our work demonstrates for the
      first time the selective concentration of MGBG by monocytes/macrophages, leading
      to the inhibition of HIV-1 expression and a reduction in proviral load within
      macrophage cultures. These results suggest that MGBG may be useful in adjunctive
      macrophage-targeted therapy for HIV infection.

PMID- 26223637
TI  - Pathogenesis and Transmission of Novel Highly Pathogenic Avian Influenza H5N2 and
      H5N8 Viruses in Ferrets and Mice.
AB  - A novel highly pathogenic avian influenza (HPAI) H5N8 virus, first detected in
      January 2014 in poultry and wild birds in South Korea, has spread throughout Asia
      and Europe and caused outbreaks in Canada and the United States by the end of the
      year. The spread of H5N8 and the novel reassortant viruses, H5N2 and H5N1 (H5Nx),
      in domestic poultry across multiple states in the United States pose a potential
      public health risk. To evaluate the potential of cross-species infection, we
      determined the pathogenicity and transmissibility of two Asian-origin H5Nx
      viruses in mammalian animal models. The newly isolated H5N2 and H5N8 viruses were
      able to cause severe disease in mice only at high doses. Both viruses replicated
      efficiently in the upper and lower respiratory tracts of ferrets; however, the
      clinical symptoms were generally mild, and there was no evidence of systemic
      dissemination of virus to multiple organs. Moreover, these influenza H5Nx viruses
      lacked the ability to transmit between ferrets in a direct contact setting. We
      further assessed viral replication kinetics of the novel H5Nx viruses in a human
      bronchial epithelium cell line, Calu-3. Both H5Nx viruses replicated to a level
      comparable to a human seasonal H1N1 virus, but significantly lower than a
      virulent Asian-lineage H5N1 HPAI virus. Although the recently isolated H5N2 and
      H5N8 viruses displayed moderate pathogenicity in mammalian models, their ability
      to rapidly spread among avian species, reassort, and generate novel strains
      underscores the need for continued risk assessment in mammals. IMPORTANCE: In
      2015, highly pathogenic avian influenza (HPAI) H5 viruses have caused outbreaks
      in domestic poultry in multiple U.S. states. The economic losses incurred with
      H5N8 and H5N2 subtype virus infection have raised serious concerns for the
      poultry industry and the general public due to the potential risk of human
      infection. This recent outbreak underscores the need to better understand the
      pathogenesis and transmission of these viruses in mammals, which is an essential
      component of pandemic risk assessment. This study demonstrates that the newly
      isolated H5N2 and H5N8 viruses lacked the ability to transmit between ferrets and
      exhibited low to moderate virulence in mammals. In human bronchial epithelial
      (Calu-3) cells, both H5N8 and H5N2 viruses replicated to a level comparable to a
      human seasonal virus, but significantly lower than a virulent Asian-lineage H5N1
      (A/Thailand/16/2004) virus. The results of this study are important for the
      evaluation of public health risk.

PMID- 26223638
TI  - The Structure of Immature Virus-Like Rous Sarcoma Virus Gag Particles Reveals a
      Structural Role for the p10 Domain in Assembly.
AB  - The polyprotein Gag is the primary structural component of retroviruses. Gag
      consists of independently folded domains connected by flexible linkers.
      Interactions between the conserved capsid (CA) domains of Gag mediate formation
      of hexameric protein lattices that drive assembly of immature virus particles.
      Proteolytic cleavage of Gag by the viral protease (PR) is required for maturation
      of retroviruses from an immature form into an infectious form. Within the
      assembled Gag lattices of HIV-1 and Mason-Pfizer monkey virus (M-PMV), the C
      terminal domain of CA adopts similar quaternary arrangements, while the N
      terminal domain of CA is packed in very different manners. Here, we have used
      cryo-electron tomography and subtomogram averaging to study in vitro-assembled,
      immature virus-like Rous sarcoma virus (RSV) Gag particles and have determined
      the structure of CA and the surrounding regions to a resolution of ~8 A. We found
      that the C-terminal domain of RSV CA is arranged similarly to HIV-1 and M-PMV,
      whereas the N-terminal domain of CA adopts a novel arrangement in which the
      upstream p10 domain folds back into the CA lattice. In this position the cleavage
      site between CA and p10 appears to be inaccessible to PR. Below CA, an extended
      density is consistent with the presence of a six-helix bundle formed by the
      spacer-peptide region. We have also assessed the affect of lattice assembly on
      proteolytic processing by exogenous PR. The cleavage between p10 and CA is indeed
      inhibited in the assembled lattice, a finding consistent with structural
      regulation of proteolytic maturation. IMPORTANCE: Retroviruses first assemble
      into immature virus particles, requiring interactions between Gag proteins that
      form a protein layer under the viral membrane. Subsequently, Gag is cleaved by
      the viral protease enzyme into separate domains, leading to rearrangement of the
      virus into its infectious form. It is important to understand how Gag is arranged
      within immature retroviruses, in order to understand how virus assembly occurs,
      and how maturation takes place. We used the techniques cryo-electron tomography
      and subtomogram averaging to obtain a detailed structural picture of the CA
      domains in immature assembled Rous sarcoma virus Gag particles. We found that
      part of Gag next to CA, called p10, folds back and interacts with CA when Gag
      assembles. This arrangement is different from that seen in HIV-1 and Mason-Pfizer
      monkey virus, illustrating further structural diversity of retroviral structures.
      The structure provides new information on how the virus assembles and undergoes
      maturation.

PMID- 26223639
TI  - Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal
      H1N1 Influenza Viruses.
AB  - Influenza viruses continue to present global threats to human health. Antigenic
      drift and shift, genetic reassortment, and cross-species transmission generate
      new strains with differences in epidemiology and clinical severity. We compared
      the temporal transcriptional responses of human dendritic cells (DC) to infection
      with two pandemic (A/Brevig Mission/1/1918, A/California/4/2009) and two seasonal
      (A/New Caledonia/20/1999, A/Texas/36/1991) H1N1 influenza viruses. Strain
      specific response differences included stronger activation of NF-kappaB following
      infection with A/New Caledonia/20/1999 and a unique cluster of genes expressed
      following infection with A/Brevig Mission/1/1918. A common antiviral program
      showing strain-specific timing was identified in the early DC response and found
      to correspond with reported transcript changes in blood during symptomatic human
      influenza virus infection. Comparison of the global responses to the seasonal and
      pandemic strains showed that a dramatic divergence occurred after 4 h, with only
      the seasonal strains inducing widespread mRNA loss. IMPORTANCE: Continuously
      evolving influenza viruses present a global threat to human health; however,
      these host responses display strain-dependent differences that are incompletely
      understood. Thus, we conducted a detailed comparative study assessing the immune
      responses of human DC to infection with two pandemic and two seasonal H1N1
      influenza strains. We identified in the immune response to viral infection both
      common and strain-specific features. Among the stain-specific elements were a
      time shift of the interferon-stimulated gene response, selective induction of NF
      kappaB signaling by one of the seasonal strains, and massive RNA degradation as
      early as 4 h postinfection by the seasonal, but not the pandemic, viruses. These
      findings illuminate new aspects of the distinct differences in the immune
      responses to pandemic and seasonal influenza viruses.

PMID- 26223640
TI  - Identification and Functional Analysis of Novel Nonstructural Proteins of Human
      Bocavirus 1.
AB  - Human bocavirus 1 (HBoV1) is a single-stranded DNA parvovirus that causes lower
      respiratory tract infections in young children worldwide. In this study, we
      identified novel splice acceptor and donor sites, namely, A1' and D1', in the
      large nonstructural protein (NS1)-encoding region of the HBoV1 precursor mRNA.
      The novel small NS proteins (NS2, NS3, and NS4) were confirmed to be expressed
      following transfection of an HBoV1 infectious proviral plasmid and viral
      infection of polarized human airway epithelium cultured at an air-liquid
      interface (HAE-ALI). We constructed mutant pIHBoV1 infectious plasmids which
      harbor silent mutations (sm) smA1' and smD1' at the A1' and D1' splice sites,
      respectively. The mutant infectious plasmids maintained production of HBoV1
      progeny virions at levels less than five times lower than that of the wild-type
      plasmid. Importantly, the smA1' mutant virus that does not express NS3 and NS4
      replicated in HAE-ALI as effectively as the wild-type virus; however, the smD1'
      mutant virus that does not express NS2 and NS4 underwent an abortive infection in
      HAE-ALI. Thus, our study identified three novel NS proteins, NS2, NS3, and NS4,
      and suggests an important function of the NS2 protein in HBoV1 replication in HAE
      ALI. IMPORTANCE: Human bocavirus 1 infection causes respiratory diseases,
      including acute wheezing in infants, of which life-threatening cases have been
      reported. In vitro, human bocavirus 1 infects polarized human bronchial airway
      epithelium cultured at an air-liquid interface that mimics the environment of
      human lower respiratory airways. Viral nonstructural proteins are often important
      for virus replication and pathogenesis in infected tissues or cells. In this
      report, we identified three new nonstructural proteins of human bocavirus 1 that
      are expressed during infection of polarized human bronchial airway epithelium.
      Among them, we proved that one nonstructural protein is critical to the
      replication of the virus in polarized human bronchial airway epithelium. The
      creation of nonreplicating infectious HBoV1 mutants may have particular utility
      in vaccine development for this virus.

PMID- 26223641
TI  - Bub1 in Complex with LANA Recruits PCNA To Regulate Kaposi's Sarcoma-Associated
      Herpesvirus Latent Replication and DNA Translesion Synthesis.
AB  - Latent DNA replication of Kaposi's sarcoma-associated herpesvirus (KSHV)
      initiates at the terminal repeat (TR) element and requires trans-acting elements,
      both viral and cellular, such as ORCs, MCMs, and latency-associated nuclear
      antigen (LANA). However, how cellular proteins are recruited to the viral genome
      is not very clear. Here, we demonstrated that the host cellular protein, Bub1, is
      involved in KSHV latent DNA replication. We show that Bub1 constitutively
      interacts with proliferating cell nuclear antigen (PCNA) via a highly conserved
      PIP box motif within the kinase domain. Furthermore, we demonstrated that Bub1
      can form a complex with LANA and PCNA in KSHV-positive cells. This strongly
      indicated that Bub1 serves as a scaffold or molecular bridge between LANA and
      PCNA. LANA recruited PCNA to the KSHV genome via Bub1 to initiate viral
      replication in S phase and interacted with PCNA to promote its monoubiquitination
      in response to UV-induced damage for translesion DNA synthesis. This resulted in
      increased survival of KSHV-infected cells. IMPORTANCE: During latency in KSHV
      infected cells, the viral episomal DNA replicates once each cell cycle. KSHV does
      not express DNA replication proteins during latency. Instead, KSHV LANA recruits
      the host cell DNA replication machinery to the replication origin. However, the
      mechanism by which LANA mediates replication is uncertain. Here, we show that
      LANA is able to form a complex with PCNA, a critical protein for viral DNA
      replication. Furthermore, our findings suggest that Bub1, a spindle checkpoint
      protein, serves as a scaffold or molecular bridge between LANA and PCNA. Our data
      further support a role for Bub1 and LANA in PCNA-mediated cellular DNA
      replication processes as well as monoubiquitination of PCNA in response to UV
      damage. These data reveal a therapeutic target for inhibition of KSHV persistence
      in malignant cells.

PMID- 26223642
TI  - R5 Macrophage-Tropic HIV-1 in the Male Genital Tract.
AB  - The entry tropism of HIV-1 Env proteins from virus isolated from the blood and
      genital tract of five men with compartmentalized lineages was determined. The Env
      proteins isolated from the genital tract of subject C018 were macrophage-tropic
      proteins, while the remaining cloned env genes encoded R5 T cell-tropic proteins.
      The detection of a macrophage-tropic lineage of HIV-1 within the male genital
      tract strongly suggests that evolution of macrophage-tropic viruses can occur in
      anatomically isolated sites outside the central nervous system.

PMID- 26223643
TI  - Innate Immune Activity Correlates with CD4 T Cell-Associated HIV-1 DNA Decline
      during Latency-Reversing Treatment with Panobinostat.
AB  - The pharmaceutical reactivation of dormant HIV-1 proviruses by histone
      deacetylase inhibitors (HDACi) represents a possible strategy to reduce the
      reservoir of HIV-1-infected cells in individuals treated with suppressive
      combination antiretroviral therapy (cART). However, the effects of such latency
      reversing agents on the viral reservoir size are likely to be influenced by host
      immune responses. Here, we analyzed the immune factors associated with changes in
      proviral HIV-1 DNA levels during treatment with the potent HDACi panobinostat in
      a human clinical trial involving 15 cART-treated HIV-1-infected patients. We
      observed that the magnitude, breadth, and cytokine secretion profile of HIV-1
      specific CD8 T cell responses were unrelated to changes in HIV-1 DNA levels in
      CD4 T cells during panobinostat treatment. In contrast, the proportions of CD3(-)
      CD56(+) total NK cells and CD16(+) CD56(dim) NK cells were inversely correlated
      with HIV-1 DNA levels throughout the study, and changes in HIV-1 DNA levels
      during panobinostat treatment were negatively associated with the corresponding
      changes in CD69(+) NK cells. Decreasing levels of HIV-1 DNA during latency
      reversing treatment were also related to the proportions of plasmacytoid
      dendritic cells, to distinct expression patterns of interferon-stimulated genes,
      and to the expression of the IL28B CC genotype. Together, these data suggest that
      innate immune activity can critically modulate the effects of latency-reversing
      agents on the viral reservoir and may represent a target for future
      immunotherapeutic interventions in HIV-1 eradication studies. IMPORTANCE:
      Currently available antiretroviral drugs are highly effective in suppressing HIV
      1 replication, but the virus persists, despite treatment, in a latent form that
      does not actively express HIV-1 gene products. One approach to eliminate these
      cells, colloquially termed the "shock-and-kill" strategy, focuses on the use of
      latency-reversing agents that induce active viral gene expression in latently
      infected cells, followed by immune-mediated killing. Panobinostat, a histone
      deacetylase inhibitor, demonstrated potent activities in reversing HIV-1 latency
      in a recent pilot clinical trial and reduced HIV-1 DNA levels in a subset of
      patients. Interestingly, we found that innate immune factors, such as natural
      killer cells, plasmacytoid dendritic cells, and the expression patterns of
      interferon-stimulated genes, were most closely linked to a decline in the HIV-1
      DNA level during treatment with panobinostat. These data suggest that innate
      immune activity may play an important role in reducing the residual reservoir of
      HIV-1-infected cells.

PMID- 26223644
TI  - RIG-I Mediates an Antiviral Response to Crimean-Congo Hemorrhagic Fever Virus.
AB  - In the cytoplasm, the retinoic acid-inducible gene I (RIG-I) senses the RNA
      genomes of several RNA viruses. RIG-I binds to viral RNA, eliciting an antiviral
      response via the cellular adaptor MAVS. Crimean-Congo hemorrhagic fever virus
      (CCHFV), a negative-sense RNA virus with a 5'-monophosphorylated genome, is a
      highly pathogenic zoonotic agent with significant public health implications. We
      found that, during CCHFV infection, RIG-I mediated a type I interferon (IFN)
      response via MAVS. Interfering with RIG-I signaling reduced IFN production and
      IFN-stimulated gene expression and increased viral replication. Immunostimulatory
      RNA was isolated from CCHFV-infected cells and from virion preparations, and RIG
      I coimmunoprecipitation of infected cell lysates isolated immunostimulatory CCHFV
      RNA. This report serves as the first description of a pattern recognition
      receptor for CCHFV and highlights a critical signaling pathway in the antiviral
      response to CCHFV. IMPORTANCE: CCHFV is a tick-borne virus with a significant
      public health impact. In order for cells to respond to virus infection, they must
      recognize the virus as foreign and initiate antiviral signaling. To date, the
      receptors involved in immune recognition of CCHFV are not known. Here, we
      investigate and identify RIG-I as a receptor involved in initiating an antiviral
      response to CCHFV. This receptor initially was not expected to play a role in
      CCHFV recognition because of characteristics of the viral genome. These findings
      are important in understanding the antiviral response to CCHFV and support
      continued investigation into the spectrum of potential viruses recognized by RIG
      I.

PMID- 26223645
TI  - Antagonistic Relationship between Human Cytomegalovirus pUL27 and pUL97
      Activities during Infection.
AB  - Human cytomegalovirus (HCMV) is a member of the betaherpesvirus family. During
      infection, an array of viral proteins manipulates the host cell cycle. We have
      previously shown that expression of HCMV pUL27 results in increased levels of the
      cyclin-dependent kinase (CDK) inhibitor p21(Cip1). In addition, pUL27 is
      necessary for the full antiviral activity of the pUL97 kinase inhibitor maribavir
      (MBV). The purpose of this study was to define the relationship between pUL27 and
      pUL97 and its role in MBV antiviral activity. We observed that expression of wild
      type but not kinase-inactive pUL97 disrupted pUL27-dependent induction of
      p21(Cip1). Furthermore, pUL97 associated with and promoted the phosphorylation of
      pUL27. During infection, inhibition of the kinase resulted in elevated levels of
      p21(Cip1) in wild-type virus but not a pUL27-deficient virus. We manipulated the
      p21(Cip1) levels to evaluate the functional consequence to MBV. Overexpression of
      p21(Cip1) restored MBV activity against a pUL27-deficient virus, while disruption
      reduced activity against wild-type virus. We provide evidence that the functional
      target of p21(Cip1) in the context of MBV activity is CDK1. One CDK-like activity
      of pUL97 is to phosphorylate nuclear lamin A/C, resulting in altered nuclear
      morphology and increased viral egress. In the presence of MBV, we observed that
      infection using a pUL27-deficient virus still altered the nuclear morphology.
      This was prevented by the addition of a CDK inhibitor. Overall, our results
      demonstrate an antagonistic relationship between pUL27 and pUL97 activities
      centering on p21(Cip1) and support the idea that CDKs can complement some
      activities of pUL97. IMPORTANCE: HCMV infection results in severe disease upon
      immunosuppression and is a leading cause of congenital birth defects. Effective
      antiviral compounds exist, yet they exhibit high levels of toxicity, are not
      approved for use during pregnancy, and can result in antiviral resistance. Our
      studies have uncovered new information regarding the antiviral efficacy of the
      HCMV pUL97 kinase inhibitor MBV as it relates to the complex interplay between
      pUL97 and a second HCMV protein, pUL27. We demonstrate that pUL97 functions
      antagonistically against pUL27 by phosphorylation-dependent inactivation of pUL27
      mediated induction of p21(Cip1). In contrast, we provide evidence that p21(Cip1)
      functions to antagonize overlapping activities between pUL97 and cellular CDKs.
      In addition, these studies further support the notion that CDK inhibitors or
      p21(Cip1) activators might be useful in combination with MBV to effectively
      inhibit HCMV infections.

PMID- 26223648
TI  - Psychiatric hospital admission and long-term care in patients with very-late
      onset schizophrenia-like psychosis.
AB  - OBJECTIVE: In this register-based study the rates and durations of psychiatric
      hospitalizations were compared between patients with very-late-onset
      schizophrenia-like psychosis (VLOSLP, n = 918) and elderly patients with illness
      onset before 60 years (n = 6142). The proportion of patients ending up in long
      term care (LTC) or long-lasting psychiatric hospital care (LLP) was also studied.
      METHODS: A sample of patients with schizophrenia aged 65 or over was collected
      from the Finnish Hospital Discharge Register. Psychiatric hospitalizations were
      calculated per year, and logistic regression was used to compare onset groups and
      factors associated with ending up in LTC/LLP. RESULTS: Between 1999 and 2003, 27%
      of patients with VLOSLP and 23% of patients with earlier onset had at least one
      psychiatric hospitalization (p = 0.020). When the rates of patients' stays in
      psychiatric hospital per year were compared, the only difference was that in the
      first year 14% (141/918) and 11% (679/6142) had at least one day in psychiatric
      hospital (p < 0.001) respectively. In logistic regression onset group of
      schizophrenia was not associated with LTC/LLP, except weakly the VLOSLP group in
      women (p = 0.042, OR 1.23). Patients having any cardiovascular disease (p <
      0.001, OR 0.63) or a respiratory disease (p = 0.008, OR 0.73) were less likely to
      end up in LTC/LLP. CONCLUSION: The patients with VLOSLP needed more psychiatric
      hospital care than those with earlier illness onset. Ending up in LTC/LLP was
      equally common in both onset groups, but some physical diseases, such as
      cardiovascular and respiratory, diminished the likelihood of this.

PMID- 26223646
TI  - Elite Control, Gut CD4 T Cell Sparing, and Enhanced Mucosal T Cell Responses in
      Macaca nemestrina Infected by a Simian Immunodeficiency Virus Lacking a gp41
      Trafficking Motif.
AB  - Deletion of Gly-720 and Tyr-721 from a highly conserved GYxxO trafficking signal
      in the SIVmac239 envelope glycoprotein cytoplasmic domain, producing a virus
      termed DeltaGY, leads to a striking perturbation in pathogenesis in rhesus
      macaques (Macaca mulatta). Infected macaques develop immune activation and
      progress to AIDS, but with only limited and transient infection of intestinal
      CD4(+) T cells and an absence of microbial translocation. Here we evaluated
      DeltaGY in pig-tailed macaques (Macaca nemestrina), a species in which SIVmac239
      infection typically leads to increased immune activation and more rapid
      progression to AIDS than in rhesus macaques. In pig-tailed macaques, DeltaGY also
      replicated acutely to high peak plasma RNA levels identical to those for
      SIVmac239 and caused only transient infection of CD4(+) T cells in the gut lamina
      propria and no microbial translocation. However, in marked contrast to rhesus
      macaques, 19 of 21 pig-tailed macaques controlled DeltaGY replication with plasma
      viral loads of <15 to 50 RNA copies/ml. CD4(+) T cells were preserved in blood
      and gut for up to 100 weeks with no immune activation or disease progression.
      Robust antiviral CD4(+) T cell responses were seen, particularly in the gut. Anti
      CD8 antibody depletion demonstrated CD8(+) cellular control of viral replication.
      Two pig-tailed macaques progressed to disease with persisting viremia and
      possible compensatory mutations in the cytoplasmic tail. These studies
      demonstrate a marked perturbation in pathogenesis caused by DeltaGY's ablation of
      the GYxxO trafficking motif and reveal, paradoxically, that viral control is
      enhanced in a macaque species typically predisposed to more pathogenic
      manifestations of simian immunodeficiency virus (SIV) infection. IMPORTANCE: The
      pathogenesis of human immunodeficiency virus (HIV) and simian immunodeficiency
      virus (SIV) reflects a balance between viral replication, host innate and
      adaptive antiviral immune responses, and sustained immune activation that in
      humans and Asian macaques is associated with persistent viremia, immune escape,
      and AIDS. Among nonhuman primates, pig-tailed macaques following SIV infection
      are predisposed to more rapid disease progression than are rhesus macaques. Here,
      we show that disruption of a conserved tyrosine-based cellular trafficking motif
      in the viral transmembrane envelope glycoprotein cytoplasmic tail leads in pig
      tailed macaques to a unique phenotype in which high levels of acute viral
      replication are followed by elite control, robust cellular responses in mucosal
      tissues, and no disease. Paradoxically, control of this virus in rhesus macaques
      is only partial, and progression to AIDS occurs. This novel model should provide
      a powerful tool to help identify host-specific determinants for viral control
      with potential relevance for vaccine development.

PMID- 26223649
TI  - Allele and haplotype frequencies of HLA-A, B, C, DRB1 and DQB1 genes in
      polytransfused patients in ethnically diverse populations from Brazil.
AB  - The red blood transfusion is a practice often used in patients with
      haematological and oncological diseases. However, the investigation of human
      leucocyte antigen (HLA) system frequency in these individuals is of great
      importance because multiple transfusions may lead to HLA alloimmunization. Brazil
      is a country that was colonized by many other ethnicities, leading to a mixed
      ethnicity and regionalized population. In view of the importance of HLA typing in
      these patients, the aim of this study was to investigate the allele and haplotype
      frequencies from polytransfused patients from three different regions from
      Brazil. HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genotyping of 366 patients was
      performed by PCR-SSO, based on the Luminex technology (One Lambda((r)) ), and the
      anti-HLA class I and class II antibodies were analysed using LabScreen Single
      Antigen Antibody Detection (One Lambda, Inc.). Allele and haplotype frequencies
      of polytransfused patients of three regions from Brazil were obtained using the
      Arlequin program. The most frequent allele frequencies observed were HLA-A*02,
      A*03, B*15, B*35, B*51, C*07, C*04, C*03, DRB1*13, DRB1*11, DRB1*07, DRB1*03,
      DRB1*01, DQB1*03, DQB1*02, DQB1*06 and DQB1*05. There were differences between
      the groups for allele variants HLA-B*57 (between Group 1 and Group 2) and HLA
      C*12 (between Group 1 and Group 3). The most frequent haplotypes found in the
      sample were HLA-A*01B*08DRB1*03, DRBI*07DQB1*02, DRB1*01DQB1*05, DRB1*13DQB1*06
      and A*02B*35. HLA class I and II antibodies were detected in 77.9% and 63.9%
      patients, respectively, while the both alloantibodies were detected in 62 (50.9%)
      patients. In conclusion, the HLA typing for polytransfused patients in each
      region has a great importance, as seen in this study; individuals from different
      regions from Brazil have HLA distribution not completely homogeneous. 

PMID- 26223647
TI  - Vaccinia Virus B1 Kinase Is Required for Postreplicative Stages of the Viral Life
      Cycle in a BAF-Independent Manner in U2OS Cells.
AB  - The vaccinia virus B1R gene encodes a highly conserved protein kinase that is
      essential for the poxviral life cycle. As demonstrated in many cell types, B1
      plays a critical role during viral DNA replication when it inactivates the
      cellular host defense effector barrier to autointegration factor (BAF or BANF1).
      To better understand the role of B1 during infection, we have characterized the
      growth of a B1-deficient temperature-sensitive mutant virus (Cts2 virus) in U2OS
      osteosarcoma cells. In contrast to all other cell lines tested to date, we found
      that in U2OS cells, Cts2 viral DNA replication is unimpaired at the nonpermissive
      temperature. However, the Cts2 viral yield in these cells was reduced more than
      10-fold, thus indicating that B1 is required at another stage of the vaccinia
      virus life cycle. Our results further suggest that the host defense function of
      endogenous BAF may be absent in U2OS cells but can be recovered through either
      overexpression of BAF or fusion of U2OS cells with mouse cells in which the
      antiviral function of BAF is active. Interestingly, examination of late viral
      proteins during Cts2 virus infection demonstrated that B1 is required for optimal
      processing of the L4 protein. Finally, execution point analyses as well as
      electron microscopy studies uncovered a role for B1 during maturation of poxviral
      virions. Overall, this work demonstrates that U2OS cells are a novel model system
      for studying the cell type-specific regulation of BAF and reveals a role for B1
      beyond DNA replication during the late stages of the viral life cycle.
      IMPORTANCE: The most well characterized role for the vaccinia virus B1 kinase is
      to facilitate viral DNA replication by phosphorylating and inactivating BAF, a
      cellular host defense responsive to foreign DNA. Additional roles for B1 later in
      the viral life cycle have been postulated for decades but are difficult to
      examine directly due to the importance of B1 during DNA replication. Here, we
      demonstrate that in U2OS cells, a B1 mutant virus escapes the block in DNA
      replication observed in other cell types and, instead, this mutant virus exhibits
      impaired late protein accumulation and incomplete maturation of new virions.
      These data provide the clearest evidence to date that B1 is needed for multiple
      critical junctures in the poxviral life cycle in a manner that is both dependent
      on and independent of BAF.

PMID- 26223650
TI  - 454-Pyrosequencing Reveals Microbial Community Structure and Composition in a
      Mesophilic UAFB System Treating PTA Wastewater.
AB  - To well understand the community structure and composition of mesophilic
      microorganisms in anaerobic system fed with PTA wastewater, an up-flow anaerobic
      fixed bed reactor was continuously run at 33 and 37  degrees C for 75 and 60
      days, respectively. Both fluorescence in situ hybridization analysis and 454
      pyrosequencing were applied to investigate the microbial distinction within
      mesophilic ranges. A preferable performance was achieved at 37 than 33  degrees
      C. The taxonomic complexities of two samples were further compared at phylum,
      class, and genus levels. Notably, microbial diversity differed a lot and the
      change of populations was observed mainly in the shared OTUs. Genus level
      analysis showed that when temperature was increased to 37  degrees C, the
      abundance of Thauera and Hydrogenophaga (beta-Proteobacteria) decreased by 93.75
      and 61.47 %, respectively, whereas that of Syntrophorhabdus (delta
      Proteobacteria) increased from 4.93 to 16.01 %. Furthermore, the dominant
      archaeal Methanobacterium at both temperatures indicated the prevailing
      contribution of hydrogenotrophic methanogens in mesophilic anaerobic system.

PMID- 26223651
TI  - IL-7/IL-7 Receptor Signaling Differentially Affects Effector CD4+ T Cell Subsets
      Involved in Experimental Autoimmune Encephalomyelitis.
AB  - IL-17-producing CD4(+) T (Th17) cells, along with IFN-gamma-expressing Th1 cells,
      represent two major pathogenic T cell subsets in experimental autoimmune
      encephalomyelitis (EAE), the animal model of multiple sclerosis (MS). The
      cytokines and transcription factors involved in the development and effector
      functions of Th1 and Th17 cells have been largely characterized. Among them, IL
      23 is essential for the generation of stable and encephalitogenic Th17 cells and
      for the development of EAE. The IL-7/IL-7R signaling axis participates in cell
      survival, and perturbation of this pathway has been associated with enhanced
      susceptibility to MS. A link between IL-23-driven pathogenic T cells and IL-7/IL
      7R signaling has previously been proposed, but has not been formally addressed.
      In the current study, we showed that Th17 cells from mice with EAE express high
      levels of IL-7Ralpha compared with Th1 cells. Using mice that constitutively
      express IL-7Ralpha on T cells, we determined that sustained IL-7R expression in
      IL-23R-deficient mice could not drive pathogenic T cells and the development of
      EAE. IL-7 inhibited the differentiation of Th17 cells, but promoted IFN-gamma and
      GM-CSF secretion in vitro. In vivo IL-7/anti-IL-7 mAb complexes selectively
      expanded and enhanced the proliferation of CXCR3-expressing Th1 cells, but did
      not impact Th17 cells and EAE development in wild-type and IL-23R-deficient mice.
      Importantly, high IL-7 expression was detected in the CNS during EAE and could
      drive the plasticity of Th17 cells to IFN-gamma-producing T cells. Together,
      these data address the contribution of IL-23/IL-23R and IL-7/IL-7R signaling in
      Th17 and Th1 cell dynamics during CNS autoimmunity.

PMID- 26223652
TI  - MicroRNAs miR-155 and miR-16 Decrease AID and E47 in B Cells from Elderly
      Individuals.
AB  - Our research in the past few years has identified B cell-specific biomarkers able
      to predict optimal Ab responses in both young and elderly individuals. These
      biomarkers are activation-induced cytidine deaminase (AID), the enzyme of class
      switch recombination and somatic hypermutation; the transcription factor E47,
      crucial for AID expression; and the ability to generate optimal memory B cells.
      Moreover, we have found that the increased proinflammatory status of the elderly,
      both in sera and intrinsic to B cells, negatively impacts B cell function. We
      have now investigated whether particular inflammatory microRNAs (miRs) contribute
      to decreased E47 and AID in aged B cells. Our data indicate that E47 and AID mRNA
      stability is lower in stimulated B cells from elderly individuals. We measured
      the expression of two miRs crucial for class switch recombination, miR-155 and
      miR-16, in human unstimulated B cells from young and elderly individuals with the
      rationale that increases in these before stimulation would decrease E47/AID upon
      cell activation. We found these miRs and B cell-intrinsic inflammation
      upregulated in aged unstimulated B cells and negatively associated with AID in
      the same B cells after stimulation with CpG. We propose that the downregulation
      of AID in aged human B cells may occur through binding of miR-155 to the 3'
      untranslated regions of AID mRNA and/or binding of miR-16 to the 3'-untranslated
      regions of E47 mRNA, as well as at the transcriptional level of less E47 for AID.
      Our results indicate novel molecular pathways leading to reduced B cell function
      with aging.

PMID- 26223653
TI  - CD36 Is Essential for Regulation of the Host Innate Response to Staphylococcus
      aureus alpha-Toxin-Mediated Dermonecrosis.
AB  - Staphylococcus aureus is the primary cause of skin and skin structure infections
      (SSSIs) in the United States. alpha-Hemolysin (Hla), a pore-forming toxin
      secreted by S. aureus and a major contributor to tissue necrosis, prompts
      recruitment of neutrophils critical for host defense against S. aureus
      infections. However, the failure to clear apoptotic neutrophils can result in
      damage to host tissues, suggesting that mechanisms of neutrophil clearance are
      essential to limiting Hla-mediated dermonecrosis. We hypothesized that CD36, a
      scavenger receptor which facilitates recognition of apoptosing cells, would play
      a significant role in regulating Hla-mediated inflammation and tissue injury
      during S. aureus SSSI. In this study, we show that CD36 on macrophages negatively
      regulates dermonecrosis caused by Hla-producing S. aureus. This regulation is
      independent of bacterial burden, as CD36 also limits dermonecrosis caused by
      intoxication with sterile bacterial supernatant or purified Hla. Dermonecrotic
      lesions of supernatant intoxicated CD36(-/-) mice are significantly larger, with
      increased neutrophil accumulation and IL-1beta expression, compared with
      CD36(+/+) (wild-type) mice. Neutrophil depletion of CD36(-/-) mice prevents this
      phenotype, demonstrating the contribution of neutrophils to tissue injury in this
      model. Furthermore, administration of CD36(+/+) but not CD36(-/-) macrophages
      near the site of intoxication reduces dermonecrosis, IL-1beta production and
      neutrophil accumulation to levels seen in wild-type mice. This therapeutic effect
      is reversed by inhibiting actin polymerization in the CD36(+/+) macrophages,
      supporting a mechanism of action whereby CD36-dependent macrophage phagocytosis
      of apoptotic neutrophils regulates Hla-mediated dermonecrosis. Taken together,
      these data demonstrate that CD36 is essential for controlling the host innate
      response to S. aureus skin infection.

PMID- 26223654
TI  - Chronic Psoriatic Skin Inflammation Leads to Increased Monocyte Adhesion and
      Aggregation.
AB  - Psoriasis patients exhibit an increased risk of death by cardiovascular disease
      (CVD) and have elevated levels of circulating intermediate (CD14(++)CD16(+))
      monocytes. This elevation could represent evidence of monocyte dysfunction in
      psoriasis patients at risk for CVD, as increases in circulating CD14(++)CD16(+)
      monocytes are predictive of myocardial infarction and death. An elevation in the
      CD14(++)CD16(+) cell population has been previously reported in patients with
      psoriatic disease, which has been confirmed in the cohort of our human psoriasis
      patients. CD16 expression was induced in CD14(++)CD16(-) classical monocytes
      following plastic adhesion, which also elicited enhanced beta2 but not beta1
      integrin surface expression, suggesting increased adhesive capacity. Indeed, we
      found that psoriasis patients have increased monocyte aggregation among
      circulating PBMCs, which is recapitulated in the KC-Tie2 murine model of
      psoriasis. Visualization of human monocyte aggregates using imaging cytometry
      revealed that classical (CD14(++)CD16(-)) monocytes are the predominant cell type
      participating in these aggregate pairs. Many of these pairs also included CD16(+)
      monocytes, which could account for apparent elevations of intermediate monocytes.
      Additionally, intermediate monocytes and monocyte aggregates were the predominant
      cell type to adhere to TNF-alpha- and IL-17A-stimulated dermal endothelium.
      Ingenuity Pathway Analysis demonstrated that monocyte aggregates have a distinct
      transcriptional profile from singlet monocytes and monocytes following plastic
      adhesion, suggesting that circulating monocyte responses to aggregation are not
      fully accounted for by homotypic adhesion, and that further factors influence
      their functionality.

PMID- 26223655
TI  - Cutting Edge: cGAS Is Required for Lethal Autoimmune Disease in the Trex1
      Deficient Mouse Model of Aicardi-Goutieres Syndrome.
AB  - Detection of intracellular DNA triggers activation of the stimulator of IFN genes
      dependent IFN-stimulatory DNA (ISD) pathway, which is essential for antiviral
      immune responses. However, chronic activation of this pathway is implicated in
      autoimmunity. Mutations in TREX1, a 3' repair exonuclease that degrades cytosolic
      DNA, cause Aicardi-Goutieres syndrome and chilblain lupus. Trex1 (-/-) mice
      develop lethal, IFN-driven autoimmune disease that is dependent on activation of
      the ISD pathway, but the DNA sensors that detect the endogenous DNA that
      accumulates in Trex1 (-/-) mice have not been defined. Multiple DNA sensors have
      been proposed to activate the ISD pathway, including cyclic GMP-AMP synthase
      (cGAS). In this study, we show that Trex1 (-/-) mice lacking cGAS are completely
      protected from lethality, exhibit dramatically reduced tissue inflammation, and
      fail to develop autoantibodies. These findings implicate cGAS as a key driver of
      autoimmune disease and suggest that cGAS inhibitors may be useful therapeutics
      for Aicardi-Goutieres syndrome and related autoimmune diseases.

PMID- 26223656
TI  - Vibrio vulnificus VvpE Stimulates IL-1beta Production by the Hypomethylation of
      the IL-1beta Promoter and NF-kappaB Activation via Lipid Raft-Dependent ANXA2
      Recruitment and Reactive Oxygen Species Signaling in Intestinal Epithelial Cells.
AB  - An inflammatory response is a hallmark of necrosis evoked by bacterial pathogens.
      Vibrio vulnificus, VvpE, is an elastase that is responsible for tissue necrosis
      and inflammation; however, the molecular mechanism by which it regulates host
      cell death has not been characterized. In the present study, we investigate the
      cellular mechanism of VvpE with regard to host cell death and the inflammatory
      response of human intestinal epithelial (INT-407) cells. The recombinant protein
      (r)VvpE (50 pg/ml) caused cytotoxicity mainly via necrosis coupled with IL-1beta
      production. The necrotic cell death induced by rVvpE is highly susceptible to the
      knockdown of annexin A (ANXA)2 and the sequestration of membrane cholesterol. We
      found that rVvpE induces the recruitment of NADPH oxidase 2 and neutrophil
      cytosolic factor 1 into membrane lipid rafts coupled with ANXA2 to facilitate the
      production of reactive oxygen species (ROS). The bacterial signaling of rVvpE
      through ROS production is uniquely mediated by the phosphorylation of redox
      sensitive transcription factor NF-kappaB. The silencing of NF-kappaB inhibited IL
      1beta production during necrosis. rVvpE induced hypomethylation and region
      specific transcriptional occupancy by NF-kappaB in the IL-1beta promoter and has
      the ability to induce pyroptosis via NOD-, LRR-, and pyrin domain-containing 3
      inflammasome. In a mouse model of V. vulnificus infection, the mutation of the
      vvpE gene from V. vulnificus negated the proinflammatory responses and maintained
      the physiological levels of the proliferation and migration of enterocytes. These
      results demonstrate that VvpE induces the hypomethylation of the IL-1beta
      promoter and the transcriptional regulation of NF-kappaB through lipid raft
      dependent ANXA2 recruitment and ROS signaling to promote IL-1beta production in
      intestinal epithelial cells.

PMID- 26223657
TI  - Small Ubiquitin-like Modifier Alters IFN Response.
AB  - IFNs orchestrate immune defense through induction of hundreds of genes. Small
      ubiquitin-like modifier (SUMO) is involved in various cellular functions, but
      little is known about its role in IFN responses. Prior work identified STAT1
      SUMOylation as an important mode of regulation of IFN-gamma signaling. In this
      study, we investigated the roles of SUMO in IFN signaling, gene expression,
      protein stability, and IFN-induced biological responses. We first show that SUMO
      overexpression leads to STAT1 SUMOylation and to a decrease in IFN-induced STAT1
      phosphorylation. Interestingly, IFNs exert a negative retrocontrol on their own
      signaling by enhancing STAT1 SUMOylation. Furthermore, we show that expression of
      each SUMO paralog inhibits IFN-gamma-induced transcription without affecting that
      of IFN-alpha. Further, we focused on IFN-induced gene products associated to
      promyelocytic leukemia (PML) nuclear bodies, and we show that neither IFN-alpha
      nor IFN-gamma could increase PML and Sp100 protein expression because they
      enhanced their SUMO3 conjugation and subsequent proteasomal degradation. Because
      it is known that SUMO3 is important for the recruitment of RING finger protein 4,
      a poly-SUMO-dependent E3 ubiquitin ligase, and that PML acts as a positive
      regulator of IFN-induced STAT1 phosphorylation, we went on to show that RING
      finger protein 4 depletion stabilizes PML and is correlated with a positive
      regulation of IFN signaling. Importantly, inhibition of IFN signaling by SUMO is
      associated with a reduction of IFN-induced apoptosis, cell growth inhibition,
      antiviral defense, and chemotaxis. Conversely, inhibition of SUMOylation results
      in higher IFN-gamma-induced STAT1 phosphorylation and biological responses.
      Altogether, our results uncover a new role for SUMO in the modulation of IFN
      response.

PMID- 26223658
TI  - Phenotypic Complexity of the Human Regulatory T Cell Compartment Revealed by Mass
      Cytometry.
AB  - Regulatory T cells (Tregs) are an essential component of the cellular immune
      response, occupying a key role in maintaining immunological tolerance and present
      an attractive therapeutic target in a range of immunopathologies. Comprehensive
      analysis of the human Treg compartment has been restricted due to technical
      limitations. The advent of mass cytometry enables simultaneous assessment of
      vastly increased phenotypic parameters at single-cell resolution. In this study,
      we used mass cytometry to examine the complexity of human Tregs using an
      extensive panel of surface markers associated with Treg function and phenotype.
      We applied unsupervised clustering analysis, revealing 22 distinct subpopulations
      of Tregs, representing previously identified and novel subpopulations. Our data
      represent the most in-depth phenotypic description of the human Treg compartment
      at single-cell resolution and show a hitherto unrecognized degree of phenotypic
      complexity among cells of the regulatory lineage.

PMID- 26223659
TI  - Venous hemostasis postcatheter ablation of atrial fibrillation while under
      therapeutic levels of oral and intravenous anticoagulation.
AB  - PURPOSE: Catheter ablation of atrial fibrillation (AF) requires utilizing
      multiple venous femoral sheaths in conjunction with aggressive periprocedural
      anticoagulation, which can lead to increased risk of vascular access
      complications. The objective of this study is to evaluate the safety and efficacy
      of the "figure-of-eight" ("F-8") suture technique for femoral venous hemostasis
      while on therapeutic doses of intravenous anticoagulation at the time of sheath
      removal. METHODS: In this case-control analysis, 376 consecutive patients
      underwent AF ablation while on uninterrupted oral anticoagulation and received
      intraprocedural heparin. In the first 253 patients (the control group), manual
      pressure was used for femoral venous hemostasis after reversal of heparin
      effects. The subsequent 123 patients (the F-8 group) had femoral venous
      hemostasis using the F-8 suture technique and while under therapeutic heparin
      effects. RESULTS: The F-8 subcutaneous suture technique achieved adequate venous
      hemostasis in 98.4% of patients. As compared to the control group, there was
      significantly less frequent utilization of the FemoStop compression assist device
      (1.2 vs. 16.8%, p < 0.0001) and in a significantly shorter interval (6.8 +/- 5.7
      vs. 50.7 +/- 12.2 min, p < 0.0001). Vascular access complications and
      thromboembolic events occurred in 9.8% in the F-8 group vs. 13.0% in the control
      group (p = 0.678). CONCLUSIONS: Immediate hemostasis of the femoral venous access
      sites after insertion of multiple sheaths for AF ablation in the presence of
      anticoagulation can be safely and effectively achieved using the F-8 suture
      technique. This technique helps minimize the period of inadequate anticoagulation
      immediately following ablation and shortens the time required to achieve adequate
      hemostasis.

PMID- 26223660
TI  - Flagellin-dependent TLR5/caveolin-1 as a promising immune activator in
      immunosenescence.
AB  - The age-associated decline of immune responses causes high susceptibility to
      infections and reduced vaccine efficacy in the elderly. However, the mechanisms
      underlying age-related deficits are unclear. Here, we found that the expression
      and signaling of flagellin (FlaB)-dependent Toll-like receptor 5 (TLR5), unlike
      the other TLRs, were well maintained in old macrophages, similar to young
      macrophages. The expression and activation of TLR5/MyD88, but not TLR4, were
      sensitively regulated by the upregulation of caveolin-1 in old macrophages
      through direct interaction. This interaction was also confirmed using macrophages
      from caveolin-1 or MyD88 knockout mice. Because TLR5 and caveolin-1 were well
      expressed in major old tissues including lung, skin, intestine, and spleen, we
      analyzed in vivo immune responses via a vaccine platform with FlaB as a mucosal
      adjuvant for the pneumococcal surface protein A (PspA) against Streptococcus
      pneumoniae infection in young and aged mice. The FlaB-PspA fusion protein induced
      a significantly higher level of PspA-specific IgG and IgA responses and
      demonstrated a high protective efficacy against a lethal challenge with live S.
      pneumoniae in aged mice. These results suggest that caveolin-1/TLR5 signaling
      plays a key role in age-associated innate immune responses and that FlaB-PspA
      stimulation of TLR5 may be a new strategy for a mucosal vaccine adjuvant against
      pneumococcal infection in the elderly. 

PMID- 26223661
TI  - Using software-modified smartphones to validate self-reported mobile phone use in
      young people: A pilot study.
AB  - A newly developed smartphone application was piloted to characterize and validate
      mobile phone use in young people. Twenty-six volunteers (mean age 17.3 years)
      from France, Spain, and the Netherlands used a software-modified smartphone for 4
      weeks; the application installed on the phone recorded number and duration of
      calls, data use, laterality, hands-free device usage, and communication system
      used for both voice calls and data transfer. Upon returning the phone,
      participants estimated their mobile phone use during those 4 weeks via an
      interviewer-administered questionnaire. Results indicated that participants on
      average underestimated the number of calls they made, while they overestimated
      total call duration. Participants held the phone for about 90% of total call time
      near the head, mainly on the side of the head they reported as dominant. Some
      limitations were encountered when comparing reported and recorded data use and
      speaker use. When applied in a larger sample, information recorded by the
      smartphone application will be very useful to improve radiofrequency (RF)
      exposure modeling from mobile phones to be used in epidemiological research.

PMID- 26223662
TI  - Mycoplasma pneumoniae and Chlamydophila pneumoniae: a comparative study in
      patients with nasal polyposis and healthy controls.
AB  - INTRODUCTION: The role played by Mycoplasma pneumoniae and Chlamydophila
      pneumoniae in the pathogenesis of chronic rhinosinusitis with nasal polyps has
      been the object of ongoing debate. We used real-time polymerase chain reaction to
      investigate the prevalence of both microorganisms in the nasal tissue samples of
      patients and controls. METHODS: We extracted DNA from nasal polyp samples
      obtained during functional endoscopic sinus surgery and the inferior turbinate
      samples of controls undergoing septoplasty. We used the highly sensitive real
      time polymerase chain reaction to detect the presence of M pneumoniae and C
      pneumoniae DNA. RESULTS: Patients with chronic rhinosinusitis with nasal polyps
      consisted of 62 individuals (39 men; mean age 51 years); the control group
      consisted of 24 individuals (13 men; mean age 45 years). All samples from both
      groups were negative for M pneumoniae and C pneumoniae DNA. CONCLUSION: We have
      demonstrated that the likelihood of M pneumoniae and C pneumoniae acting as an
      ongoing inflammatory stimulus in chronic rhinosinusitis with nasal polyps is
      slim.

PMID- 26223663
TI  - Optimal composite scores for longitudinal clinical trials under the linear mixed
      effects model.
AB  - Clinical trials of chronic, progressive conditions use rate of change on
      continuous measures as the primary outcome measure, with slowing of progression
      on the measure as evidence of clinical efficacy. For clinical trials with a
      single prespecified primary endpoint, it is important to choose an endpoint with
      the best signal-to-noise properties to optimize statistical power to detect a
      treatment effect. Composite endpoints composed of a linear weighted average of
      candidate outcome measures have also been proposed. Composites constructed as
      simple sums or averages of component tests, as well as composites constructed
      using weights derived from more sophisticated approaches, can be suboptimal, in
      some cases performing worse than individual outcome measures. We extend recent
      research on the construction of efficient linearly weighted composites by
      establishing the often overlooked connection between trial design and composite
      performance under linear mixed effects model assumptions and derive a formula for
      calculating composites that are optimal for longitudinal clinical trials of
      known, arbitrary design. Using data from a completed trial, we provide example
      calculations showing that the optimally weighted linear combination of scales can
      improve the efficiency of trials by almost 20% compared with the most efficient
      of the individual component scales. Additional simulations and analytical results
      demonstrate the potential losses in efficiency that can result from alternative
      published approaches to composite construction and explore the impact of weight
      estimation on composite performance.

PMID- 26223664
TI  - Native gel analysis of macromolecular protein complexes in cultured mammalian
      cells.
AB  - Native gel electrophoresis enables separation of cellular proteins in their non
      denatured state. In experiments aimed at analysing proteins in higher order or
      multimeric assemblies (i.e. protein complexes) it offers some advantages over
      rival approaches, particularly as an interface technology with mass spectrometry.
      Here we separated fractions from HEK293 cells by native electrophoresis in order
      to survey protein complexes in the cytoplasmic, nuclear and chromatin
      environments, finding 689 proteins distributed among 217 previously described
      complexes. As expected, different fractions contained distinct combinations of
      macromolecular complexes, with subunits of the same complex tending to co
      migrate. Exceptions to this observation could often be explained by the presence
      of subunits shared among different complexes. We investigated one identified
      complex, the Polycomb Repressor Complex 2 (PRC2), in more detail following
      affinity purification of the EZH2 subunit. This approach resulted in the
      identification of all previously reported members of PRC2. Overall, this work
      demonstrates that the use of native gel electrophoresis as an upstream separating
      step is an effective approach for analysis of the components and cellular
      distribution of protein complexes. 

PMID- 26223665
TI  - Temperature-Jump Fluorescence Provides Evidence for Fully Reversible Microsecond
      Dynamics in a Thermophilic Alcohol Dehydrogenase.
AB  - Protein dynamics on the microsecond (MUs) time scale were investigated by
      temperature-jump fluorescence spectroscopy as a function of temperature in two
      variants of a thermophilic alcohol dehydrogenase: W87F and W87F:H43A. Both
      mutants exhibit a fast, temperature-independent MUs decrease in fluorescence
      followed by a slower full recovery of the initial fluorescence. The results,
      which rule out an ionizing histidine as the origin of the fluorescence quenching,
      are discussed in the context of a Trp49-containing dimer interface that acts as a
      conduit for thermally activated structural change within the protein interior. 

PMID- 26223666
TI  - [Papillary tumors - therapeutic concepts].
AB  - Papillary tumors originate from the various structures of the ampulla of Vater;
      therefore, these rare tumors represent a heterogeneous group of tumor entities.
      Intestinal differentiated adenomas are the most common benign lesions, whereas
      intestinal differentiated papillary carcinomas are the most common malignant
      tumors. Carcinomas with pancreaticobiliary differentiation have a poorer
      prognosis. Mesenchymal and neuroendocrine tumors are among the least frequent
      papillary tumors. Diagnosis is performed by side-view upper endoscopy and biopsy.
      In cases of suspected malignancy a complete staging with computed tomography (CT)
      and endoscopic ultrasound scanning is indicated to determine local tumor
      spread.Adenomas are removed by endoscopic snare papillectomy whereas the therapy
      of choice for papillary carcinomas is pancreatic head resection with systematic
      lymphadenectomy. Patients with papillary carcinomas are most likely to benefit
      from adjuvant therapy, which should be determined in an interdisciplinary
      consensus conference considering the histological differentiation of the tumor. 

PMID- 26223667
TI  - [Not Available].

PMID- 26223668
TI  - [Lymph node dissection after primary surgery and neoadjuvant radiochemotherapy of
      rectal cancer. Interim analysis of a multicenter prospective observational study
      (OCUM)].
AB  - INTRODUCTION: The OCUM trial (NCT01325649) aims to clarify whether low rates of
      local recurrence are also achieved when the indications for neoadjuvant
      radiochemotherapy are not based on the clinical TNM staging but on preoperative
      magnetic resonance imaging with measurement of the tumor distance to the
      circumferential resection margin. In this interim analysis the lymph node status
      in OCUM patients was investigated as a surrogate parameter for quality of surgery
      and histopathological work-up. MATERIAL AND METHODS: Until now a total of 560
      patients have been included in this study. Total mesorectal excision (TME)
      without pretreatment was undertaken in 338 patients (60.4 %) and neoadjuvant
      radiochemotherapy was administered in 222 (39.6 %) patients. The histological
      work-up was performed according to the guidelines of the German Association of
      Pathologists. Data are given as median values and ranges in brackets. RESULTS:
      The lymph node yield was 24 (7-79) in 338 patients undergoing primary TME surgery
      without pretreatment, while 20 (3-56) lymph nodes were identified in patients
      after neoadjuvant radiochemotherapy (p = 0.001). A minimum of 12 lymph nodes were
      analyzed in 335 out of 338 patients (99.1 %) and in 209 out of 222 patients (94.1
      %) following neoadjuvant radiochemotherapy (p = 0.001). Lymph node metastasis was
      identified (p = 0.362) in 116 out of 338 patients without pretreatment (34.3 %)
      and in 71 out of 222 patients after neoadjuvant radiochemotherapy (32.0 %).
      Patient age did not influence the number of identified lymph nodes or rate of
      lymph node metastasis. CONCLUSION: In this trial the number of identified lymph
      nodes suggests that the quality of surgery and histopathological work-up were
      adequate compared to the standards defined by national guidelines. Neoadjuvant
      radiochemotherapy led to a reduced lymph node yield compared to surgery without
      pretreatment; however, this did not influence the rate of lymph node metastasis.

PMID- 26223669
TI  - [Report of 12 years experience in the surgical treatment of 286 paraesophageal
      hernias].
AB  - BACKGROUND: In contrast to axial hiatus hernias, paraesophageal hernias are rare
      but can lead to chronic iron deficiency anemia and severe acute complications.
      Treatment is manifold and consistent standards are lacking. OBJECTIVES: The aim
      of this study was to describe our experiences of 286 patients with paraesophageal
      hernias, who underwent surgery from 2003 to 2014 at a tertiary referral center.
      The study was particularly concerned with morbidity, mortality, quality of life
      and recurrence rates. MATERIAL AND METHODS: In 12 years a total of 286
      paraesophageal hernias were surgically treated, 255 with a minimally invasive
      procedure and 31 with an open approach. In 138 patients (48 %) the suture-based
      hiatoplasty was reinforced by means of a lightweight mesh, which was fixed with
      fibrin glue in 90 cases. Abdominal fixation of the stomach consisted of a
      gastropexy and anterior (n = 244) or posterior (n = 42) fundoplication. RESULTS:
      Complications arose in 8.4 % of the patients. The mean hospital stay was 5.3 (+/-
      2.8) days for elective surgery and 24.7 (+/- 17.8) days for emergency operations.
      The gastrointestinal quality of life index according to Eypasch significantly
      increased from mean preoperative values of 92.8 (+/- 22.5) to 109.6 (+/- 20.2) in
      the postoperative course (p < 0.001). Of the patients 20 (7 %) suffered a
      recurrence requiring surgery, including 7 early and 13 late recurrences. During
      the immediate postoperative period radiographically detected recurrences were
      promptly revised. The strategy of late recurrences in the long-term course was
      based on patient symptoms and asymptomatic hernias were treated conservatively
      while symptomatic hernias were surgically treated. Symptomatic late recurrences
      developed in 4.6 % of the patients, including 7.4 % (11 out of 148) without and
      1.4 % (2 out of 138) with primary mesh repair. CONCLUSION: The repair of
      paraesophageal hernias in 286 patients provided excellent patient satisfaction
      and symptom improvement with low perioperative morbidity and mortality. Mesh
      reinforcement reduced the recurrence rate. The quality of life index is a
      suitable clinical course parameter for evaluation of paraesophageal hernias.

PMID- 26223670
TI  - [Minimally invasive esophagus resection: Results of a prospective multicenter
      study].

PMID- 26223671
TI  - [Treatment of recurrent hepatocellular cancer after liver resection].

PMID- 26223672
TI  - [Adrenocortical tumors > 8 cm should be treated by open surgery].

PMID- 26223673
TI  - Efficacy of multiple microwave endometrial ablation technique for menorrhagia
      resulting from adenomyosis.
AB  - AIM: Conventional microwave endometrial ablation (MEA) can be insufficient to
      control menorrhagia resulting from adenomyosis. We compared the standard single
      ablation technique with multiple MEA - repeating ablation three times in the same
      region - in patients with adenomyosis and menorrhagia. MATERIAL AND METHODS: We
      performed single MEA in 18 patients and multiple MEA in seven patients between
      2007 and 2013. We compared the efficacy of single and multiple MEA using a visual
      analog scale (VAS) for menorrhagia, dysmenorrhea, and patient satisfaction. We
      also evaluated the incidence of menorrhagia recurrence, amenorrhea, and procedure
      complications in relation to patients' clinical factors. RESULTS: VAS scores for
      improved menorrhagia and patient satisfaction were significantly higher in the
      multiple MEA group than in the single MEA group; however, the operative time was
      longer in the multiple-treatment group. There were no statistical differences
      between groups in hemoglobin levels, VAS improvement for dysmenorrhea,
      menorrhagia recurrence, frequency of complications, or amenorrhea rate.
      CONCLUSION: Multiple MEA successfully controls menorrhagia from adenomyosis and
      achieves a higher satisfaction rate than single MEA.

PMID- 26223674
TI  - Merging open metal sites and Lewis basic sites in a NbO-type metal-organic
      framework for improved C2H2/CH4 and CO2/CH4 separation.
AB  - A new three-dimensional NbO-type porous metal-organic framework ZJNU-47 was
      synthesized via a solvothermal reaction of Cu(NO3)2.3H2O and a Lewis basic
      nitrogen donor site-rich tetracarboxylate, namely, 5,5'-(pyridazine-3,6-diyl)
      diisophthalate, and the structure was characterized by single-crystal X-ray
      diffraction to be isostructural with NOTT-101. With the synergistic effect of
      open metal sites, Lewis basic sites and a suitable pore space, the MOF material
      ZJNU-47a after activation can take up a large amount of C2H2 and CO2. The
      gravimetric C2H2 uptake of 214 cm(3) (STP) g(-1) at room temperature and 1 atm is
      the highest among all reported MOFs to date, and the gravimetric CO2 uptake of
      108 cm(3) (STP) g(-1) is also among the highest reported for MOFs. Compared to
      the isostructural MOF NOTT-101a, ZJNU-47a exhibits a significant increase in C2H2
      and CO2 uptake and thus improved C2H2/CH4 and CO2/CH4 separations. Significantly,
      comprehensive DFT studies of C2H2 and CO2 adsorption have revealed that the open
      nitrogen donor sites are comparable and even superior to open metal sites
      regarding the adsorption sites. This work demonstrated that the simultaneous
      introduction of Lewis basic nitrogen donor sites and Lewis acidic metal sites
      into the framework is a promising approach to improve the gas sorption toward CO2
      and C2H2 and thus to produce materials possessing enhanced C2H2/CH4 and CO2/CH4
      separation performance. 

PMID- 26223675
TI  - Maternal and neonatal outcomes in pregnant women with PCOS: comparison of
      different diagnostic definitions.
AB  - STUDY QUESTION: Does the prevalence of adverse maternal and neonatal outcomes
      vary in women diagnosed with polycystic ovary syndrome (PCOS) according to
      different definitions? SUMMARY ANSWER: A comparison of different criteria
      revealed that there is a substantial risk for perinatal complications in PCOS
      women, regardless of the used definition. WHAT IS KNOWN ALREADY: Pregnant women
      with PCOS are susceptible to perinatal complications. At present, there are three
      main definitions for PCOS. So far, we are aware of only one study, which found
      that the elevated risk for complications varied widely depending on the different
      phenotypes and features but only considered a relatively small sample size for
      some of the phenotypes. STUDY DESIGN, SIZE, DURATION: Retrospective matched
      cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data of primiparous women
      with PCOS according to ESHRE/ASRM 2003 criteria and healthy controls giving birth
      to neonates >=500 g were included. A total of 885 women were analysed: out of 177
      women with PCOS, 85 (48.0%) met the National Institutes of Health (NIH) 1990
      criteria, another 14 (7.9%) featured the additional phenotypes defined by The
      Androgen Excess and PCOS Society (AE-PCOS) 2006 criteria, 78 (44.1%) were
      classified as PCOS exclusively by the ESHRE/ASRM 2003 definition, and 708
      represented the control group. MAIN RESULTS AND THE ROLE OF CHANCE: The
      prevalence of adverse maternal (49.4 versus 64.3 versus 60.3%, P = 0.313) and
      neonatal (27.1 versus 35.7 versus 23.1%, P = 0.615) outcomes did not differ
      within the three PCOS groups (ESHRE/ASRM, NIH, AE-PCOS, respectively). Compared
      with healthy controls, the risk for maternal complications was increased in PCOS
      patients [odds ratio (OR) 2.57; 95% confidence interval (CI) 1.82-3.64; P <
      0.001] while there was no difference in neonatal complications (OR 0.83; 95% CI
      0.56-1.21; P = 0.343). LIMITATIONS, REASONS FOR CAUTION: A limitation of our
      study is its retrospective design and the relatively small sample size,
      particularly in the AE-PCOS subgroup. WIDER IMPLICATIONS OF THE FINDINGS: Since
      women with PCOS have, regardless of the used definition, a high risk of maternal
      and neonatal complications they should be informed and advised to follow regular
      checks in units where problems can be detected early to allow specialized care.
      STUDY FUNDING/COMPETING INTERESTS: Marietta Blau Grant (Austrian Agency for
      International Cooperation in Education and Research; OeAD-GmbH) and mobility
      scholarship (Medical University of Graz).

PMID- 26223676
TI  - Chromosome segregation regulation in human zygotes: altered mitotic histone
      phosphorylation dynamics underlying centromeric targeting of the chromosomal
      passenger complex.
AB  - STUDY QUESTION: Are the kinase feedback loops that regulate activation and
      centromeric targeting of the chromosomal passenger complex (CPC), functional
      during mitosis in human embryos? SUMMARY ANSWER: Investigation of the regulatory
      kinase pathways involved in centromeric CPC targeting revealed normal
      phosphorylation dynamics of histone H2A at T120 (H2ApT120) by Bub1 kinase and
      subsequent recruitment of Shugoshin, but phosphorylation of histone H3 at
      threonine 3 (H3pT3) by Haspin failed to show the expected centromeric enrichment
      on metaphase chromosomes in the zygote. WHAT IS KNOWN ALREADY: Human cleavage
      stage embryos show high levels of chromosomal instability. What causes this high
      error rate is unknown, as mechanisms used to ensure proper chromosome segregation
      in mammalian embryos are poorly described. STUDY DESIGN, SIZE, DURATION: In this
      study, we investigated the pathways regulating CPC targeting to the inner
      centromere in human embryos. We characterized the distribution of the CPC in
      relation to activity of its two main centromeric targeting pathways: the Bub1
      H2ApT120-Sgo-CPC and Haspin-H3pT3-CPC pathways. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: The study was conducted between May 2012 and March 2014 on human surplus
      embryos resulting from in vitro fertilization treatment and donated for research.
      In zygotes, nuclear envelope breakdown was monitored by time-lapse imaging to
      allow timed incubations with specific inhibitors to arrest at prometaphase and
      metaphase, and to interfere with Haspin and Aurora B/C kinase activity.
      Functionality of the targeting pathways was assessed through characterization of
      histone phosphorylation dynamics by immunofluorescent analysis, combined with
      gene expression by RT-qPCR and immunofluorescent localization of key pathway
      proteins. MAIN RESULTS AND THE ROLE OF CHANCE: Immunofluorescent analysis of the
      CPC subunit Inner Centromere Protein revealed the pool of stably bound CPC
      proteins was not strictly confined to the inner centromere of prometaphase
      chromosomes in human zygotes, as observed in later stages of preimplantation
      development and somatic cells. Investigation of the regulatory kinase pathways
      involved in centromeric CPC targeting revealed normal phosphorylation dynamics of
      histone H2A at T120 (H2ApT120) by Bub1 kinase and subsequent recruitment of
      Shugoshin. However, phosphorylation of histone H3 at threonine 3 (H3pT3) by
      Haspin kinase failed to show the expected centromeric enrichment on metaphase
      chromosomes in the zygote, but not at later stages. Inhibition of Haspin revealed
      this activity to be essential for proper mitotic checkpoint complex activation in
      human zygotes, thus demonstrating an active mitotic checkpoint under normal
      conditions. Abolishment of H3pT3 during zygotic prometaphase further shows that
      centromeric H2ApT120 alone is not sufficient for proper shugoshin and CPC
      localization. As the removal of H3pT3 from the chromosome arms during
      prometaphase normally contributes to further centromeric enrichment of the CPC in
      somatic cells, CPC targeting may be less accurate in human zygotes. LIMITATIONS,
      REASONS FOR CAUTION: Owing to ethical limitations, tripronuclear zygotes were
      used in functional experiments. Although these represent the best available
      models, it is unknown if they are completely representative for dipronuclear
      zygotes. In addition, further research is needed to determine to what extent the
      differences we observed in H3T3 phosphorylation dynamics and CPC localization
      affect chromosome attachment. WIDER IMPLICATIONS OF THE FINDINGS: In the zygote,
      paternal and maternal chromosomes coming from two separate pronuclei, and with
      contrasting epigenetic signatures, need to be aligned on a single metaphase
      plate. Our results suggest that adaptations in mechanisms regulating CPC
      targeting exist in the human zygote, to ensure symmetric recruitment despite the
      epigenetic asymmetry between maternal and paternal chromosomes. This adaptation
      may come at a price regarding chromosome segregation fidelity. STUDY
      FUNDING/COMPETING INTERESTS: This study was funded by the Portuguese Fundacao
      para a Ciencia e Tecnologia and the Netherlands Organization for Scientific
      Research. The authors have no conflicts of interest to declare.

PMID- 26223678
TI  - Effect of fluid-colloid interactions on the mobility of a thermophoretic
      microswimmer in non-ideal fluids.
AB  - Janus colloids propelled by light, e.g., thermophoretic particles, offer
      promising prospects as artificial microswimmers. However, their swimming behavior
      and its dependence on fluid properties and fluid-colloid interactions remain
      poorly understood. Here, we investigate the behavior of a thermophoretic Janus
      colloid in its own temperature gradient using numerical simulations. The
      dissipative particle dynamics method with energy conservation is used to
      investigate the behavior in non-ideal and ideal-gas like fluids for different
      fluid-colloid interactions, boundary conditions, and temperature-controlling
      strategies. The fluid-colloid interactions appear to have a strong effect on the
      colloid behavior, since they directly affect heat exchange between the colloid
      surface and the fluid. The simulation results show that a reduction of the heat
      exchange at the fluid-colloid interface leads to an enhancement of colloid's
      thermophoretic mobility. The colloid behavior is found to be different in non
      ideal and ideal fluids, suggesting that fluid compressibility plays a significant
      role. The flow field around the colloid surface is found to be dominated by a
      source-dipole, in agreement with the recent theoretical and simulation
      predictions. Finally, different temperature-control strategies do not appear to
      have a strong effect on the colloid's swimming velocity. 

PMID- 26223677
TI  - Expression of melanocortin receptors in human endometrium.
AB  - STUDY QUESTION: Are melanocortin receptors (MCR1-5) expressed in the endometrium?
      SUMMARY ANSWER: MCR1-5 are expressed in endometrium to varying degrees, with
      MC2R, MC3R and MC5R being the most abundant and the majority of expression being
      observed in glandular epithelium. WHAT IS KNOWN ALREADY: Women with Addison's
      disease who were being administered synthetic ACTH reported menstrual
      complications as a side effect. There is no previous literature on expression of
      the melanocortin receptors within the endometrium, and therefore whether ACTH may
      directly affect the endometrial vasculature. STUDY DESIGN, SIZE, DURATION:
      Endometrial biopsies were taken from hysterectomy specimens in control women
      without endometrial pathology (n = 4 for each of proliferative and late-secretory
      phases). Biopsies were formalin fixed and embedded in paraffin wax. Decidual
      samples (n = 7) were cultured in a range of concentrations of synthetic ACTH for
      3 days before being formalin fixed and embedded in paraffin wax.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial paraffin embedded sections
      were immunostained for MCR1-5 and assessed using a modified quickscore with
      luminal epithelium, glandular epithelium, stromal cells, endothelial cells and
      vascular smooth muscle cells all being assessed separately. Cultured decidual
      biopsy paraffin embedded sections were immunostained for H-caldesmon and the
      number of layers of vascular smooth muscle cells surrounding the vessel assessed.
      MAIN RESULTS AND THE ROLE OF CHANCE: All five melanocortin receptors were shown
      to be immunolocalised to the endometrium, with MC5R, MC2R and MC3R being the most
      abundant and limited immunostaining being observed for MC1R and MC4R. Treatment
      of decidual biopsies with synthetic adrenocorticotropin (ACTH) resulted in loss
      of vascular integrity. LIMITATIONS, REASONS FOR CAUTION: This is an observational
      study and does not definitively demonstrate a link between synthetic ACTH
      administration and menstrual complications. WIDER IMPLICATIONS OF THE FINDINGS:
      This is the first study to demonstrate widespread expression of melanocortin
      receptors within the endometrium. Further study is required to determine the role
      of this hormone family in endometrial function. STUDY FUNDING/COMPETING
      INTERESTS: The work was part funded by MRC grant G09000001. The authors have no
      competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 26223679
TI  - An IVC filter and anticoagulation for 3 months is unlikely to show a benefit over
      anticoagulation alone for high-risk patients with acute pulmonary embolism.

PMID- 26223680
TI  - Day case surgery: a good news story for the NHS.

PMID- 26223681
TI  - Rehabilitation Interventions for Improving Social Participation After Stroke: A
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: Despite the fact that social participation is considered a pivotal
      outcome of a successful recovery after stroke, there has been little attention on
      the impact of activities and services on this important domain. OBJECTIVE: To
      present a systematic review and meta-analysis from randomized controlled trials
      (RCTs) on the effects of rehabilitation interventions on social participation
      after stroke. METHODS: A total of 8 electronic databases were searched for
      relevant RCTs that evaluated the effects of an intervention on the outcome of
      social participation after stroke. Reference lists of selected articles were hand
      searched to identify further relevant studies. The methodological quality of the
      studies was assessed using the Physiotherapy Evidence Database Scale.
      Standardized mean differences (SMDs) and confidence intervals (CIs) were
      estimated using fixed- and random-effect models. RESULTS: In all, 24 RCTs
      involving 2042 stroke survivors were identified and reviewed, and 21 were
      included in the meta-analysis. There was a small beneficial effect of
      interventions that utilized exercise on social participation (10 studies; SMD =
      0.43; 95% CI = 0.09, 0.78;P= .01) immediately after the program ended. Exercise
      in combination with other interventions (13 studies; SMD = 0.34; 95% CI = 0.10,
      0.58;P= .006) also resulted in beneficial effects. No significant effect was
      observed for interventions that involved support services over 9 studies (SMD =
      0.09 [95% CI = -0.04, 0.21];I(2)= 0%;P= .16). CONCLUSIONS: The included studies
      provide evidence that rehabilitation interventions may be effective in improving
      social participation after stroke, especially if exercise is one of the
      components.

PMID- 26223682
TI  - Stratifin accelerates progression of lung adenocarcinoma at an early stage.
AB  - BACKGROUNDS: Adenocarcinoma in situ (AIS) of the lung has an extremely favorable
      prognosis. However, early but invasive adenocarcinoma (eIA) sometimes has a fatal
      outcome. We had previously compared the expression profiles of AIS with those of
      eIA showing lymph node metastasis or a fatal outcome, and found that stratifin
      (SFN, 14-3-3 sigma) was a differentially expressed gene related to cell
      proliferation. Here, we performed an in vivo study to clarify the role of SFN in
      initiation and progression of lung adenocarcinoma. FINDINGS: Suppression of SFN
      expression in A549 (a human lung adenocarcinoma cell line) by siSFN significantly
      reduced cell proliferation activity and the S-phase subpopulation. In vivo, tumor
      development or metastasis to the lung was reduced in shSFN-transfected A549
      cells. Moreover, we generated SFN-transgenic mice (Tg-SPC-SFN(+/-)) showing lung
      specific expression of human SFN under the control of a tissue-specific enhancer,
      the SPC promoter. We found that Tg-SPC-SFN(+/-) mice developed lung tumors at a
      significantly higher rate than control mice after administration of chemical
      carcinogen, NNK. Interestingly, several Tg-SPC-SFN(+/-) mice developed tumors
      without NNK. These tumor cells showed high hSFN expression. CONCLUSION: These
      results suggest that SFN facilitates lung tumor development and progression. SFN
      appears to be a novel oncogene with potential as a therapeutic target.

PMID- 26223683
TI  - Mutations of short tandem repeat loci in cases of paternity testing in Chinese.
AB  - In order to find out the characteristics of genetic mutations in 15 short tandem
      repeat (STR) loci, 3734 parentage cases were analyzed using AmpFlSTR Sinofiler
      kit. The allele source, mutation rate, and mutation rule of the STR loci were
      determined. Seventy mutations were observed in all cases for paternity testing.
      Among 15 STR loci, the highest mutation rate was observed in D12S391 (0.21 %),
      but the D5S818 gene mutation rate was relatively low (0.02 %). One-step mutation
      cases accounted for 95.7 % of all of the cases monitored. And the mutations in
      this study mainly showed paternal mutation (64/70). The research results are of
      great significance for identification and paternity tests and for the improvement
      of genetic studies on Chinese population in the future. 

PMID- 26223684
TI  - Falsely elevated capillary glucose and ketone levels and use of skin lightening
      creams.

PMID- 26223685
TI  - Optimization protocol for the extraction of 6-gingerol and 6-shogaol from
      Zingiber officinale var. rubrum Theilade and improving antioxidant and anticancer
      activity using response surface methodology.
AB  - BACKGROUND: Analysis and extraction of plant matrices are important processes for
      the development, modernization, and quality control of herbal formulations.
      Response surface methodology is a collection of statistical and mathematical
      techniques that are used to optimize the range of variables in various
      experimental processes to reduce the number of experimental runs, cost , and
      time, compared to other methods. METHODS: Response surface methodology was
      applied for optimizing reflux extraction conditions for achieving high 6-gingerol
      and 6-shogaol contents, and high antioxidant activity in Zingiber officinale var.
      rubrum Theilade . The two-factor central composite design was employed to
      determine the effects of two independent variables, namely extraction temperature
      (X1: 50-80  degrees C) and time (X2: 2-4 h), on the properties of the extracts.
      The 6-gingerol and 6-shogaol contents were measured using ultra-performance
      liquid chromatography. The antioxidant activity of the rhizome extracts was
      determined by means of the 1,1-diphenyl-2-picrylhydrazyl assay. Anticancer
      activity of optimized extracts against HeLa cancer cell lines was measured using
      MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.
      RESULTS: Increasing the extraction temperature and time induced significant
      response of the variables. The optimum extraction condition for all responses was
      at 76.9  degrees C for 3.4 h. Under the optimum condition, the corresponding
      predicted response values for 6-gingerol, 6-shogaol, and the antioxidant activity
      were 2.89 mg/g DW, 1.85 mg/g DW, and 84.3%, respectively. 6-gingerol and 6
      shogaol were extracted under optimized condition to check the viability of the
      models. The values were 2.92 and 1.88 mg/g DW, and 84.0% for 6-gingerol, 6
      shogaol, and the antioxidant activity respectively. The experimental values
      agreed with those predicted, thus indicating suitability of the models employed
      and the success of RSM in optimizing the extraction condition. With optimizing of
      reflux extraction anticancer activity of extracts against HeLa cancer cells
      enhanced about 16.8%. The half inhibition concentration (IC50) value of optimized
      and unoptimized extract was found at concentration of 20.9 and 38.4 MUg/mL
      respectively. Optimized extract showed more distinct anticancer activities
      against HeLa cancer cells in a concentration of 40 MUg/mL (P < 0.01) without
      toxicity to normal cells. CONCLUSIONS: The results indicated that the
      pharmaceutical quality of ginger could be improved significantly by optimizing of
      extraction process using response surface methodology.

PMID- 26223686
TI  - Monocyte chemotactic protein-1 elevation prior to the onset of rheumatoid
      arthritis among women.
AB  - OBJECTIVE: To examine monocyte chemotactic protein-1 (MCP-1) concentration and
      future rheumatoid arthritis (RA) risk, and investigate effect modification by
      human leukocyte antigen-shared epitope (HLA-SE) and several lifestyle factors.
      METHODS: We conducted a nested case-control study using stored plasma samples
      from the Nurses' Health Studies. Each pre-RA case was matched to three controls
      (N case = 220, N control = 675). Odds ratios (OR) for RA associated with MCP-1
      concentration and interactions with HLA-SE, smoking, BMI and alcohol intake were
      estimated. RESULTS: MCP-1 concentration was associated with both seropositive and
      seronegative RA, in particular <5 years of blood draw (OR: 2.42), and among HLA
      SE positive (OR: 2.05). No interactions with smoking, BMI or alcohol were
      detected. CONCLUSION: MCP-1 was associated with risk of RA, especially among HLA
      SE positive, but did not differ by smoking status, BMI or alcohol intake.

PMID- 26223687
TI  - Perception of drinking water safety and factors influencing acceptance and
      sustainability of a water quality intervention in rural southern India.
AB  - BACKGROUND: Acceptance and long-term sustainability of water quality
      interventions are pivotal to realizing continued health benefits. However, there
      is limited research attempting to understand the factors that influence
      compliance to or adoption of such interventions. METHODS: Eight focus group
      discussions with parents of young children--including compliant and not compliant
      households participating in an intervention study, and three key-informant
      interviews with village headmen were conducted between April and May 2014 to
      understand perceptions on the effects of unsafe water on health, household
      drinking water treatment practices, and the factors influencing acceptance and
      sustainability of an ongoing water quality intervention in a rural population of
      southern India. RESULTS: The ability to recognize health benefits from the
      intervention, ease of access to water distribution centers and the willingness to
      pay for intervention maintenance were factors facilitating acceptance and
      sustainability of the water quality intervention. On the other hand, faulty
      perceptions on water treatment, lack of knowledge about health hazards associated
      with drinking unsafe water, false sense of protection from locally available
      water, resistance to change in taste or odor of water and a lack of support from
      male members of the household were important factors impeding acceptance and long
      term use of the intervention. CONCLUSION: This study highlights the need to
      effectively involve communities at important stages of implementation for long
      term success of water quality interventions. Timely research on the factors
      influencing uptake of water quality interventions prior to implementation will
      ensure greater acceptance and sustainability of such interventions in low income
      settings.

PMID- 26223688
TI  - Factors associated with spontaneous preterm birth risk assessed by transvaginal
      ultrasound following cervical cerclage.
AB  - OBJECTIVE: To determine the predictive value of various cervical length
      measurements postcerclage for the outcome of preterm birth following both
      elective and rescue cerclage. MATERIALS AND METHODS: Over a five-year period, we
      identified 59 women who had a transvaginal cerclage inserted followed by serial
      cervical length measurement. Of these, 18 were elective cerclages placed at 14
      weeks of gestation on the basis of a history of cervical insufficiency and 41
      were rescue cerclages performed at gestations ranging from 17 to 23 weeks
      following a diagnosis of shortened cervix on ultrasound. The women were
      asymptomatic throughout. RESULTS: There was a strong correlation between cervical
      length postcerclage and gestation at delivery. For both groups, preterm birth
      could be predicted by the total cervical length. In the rescue cerclage group,
      the change in cervical length was predictive, with positive changes associated
      with later gestation at delivery. The presence of funnelling was predictive of
      preterm birth in the elective cerclage group only. CONCLUSION: Transvaginal
      cervical length measurement is useful in the prediction of preterm birth
      postcerclage placement. Serial cervical length measurement postcerclage may
      assist with timely addition of interventions such, progesterone and antenatal
      cortico steroids for fetal lung maturation.

PMID- 26223689
TI  - The quality of economic evaluations of ultra-orphan drugs in Europe - a
      systematic review.
AB  - An orphan disease is defined in the EU as a disorder affecting less than 1 in 2
      000 individuals. The concept of ultra-orphan has been proposed for diseases with
      a prevalence of less than 1:50 000. Drugs for ultra-orphan diseases are amongst
      the most expensive medicines on a cost-per-patient basis. The extremely high
      prices have prompted initiatives to evaluate cost-effectiveness and cost-utility
      in EU-member states. The objective of this review was to evaluate the quality of
      cost-effectiveness and cost-utility studies on ultra-orphan drugs. We searched 2
      databases and the reference lists of relevant systematic reviews. Studies
      reporting on full economic evaluations, or at least aiming at such evaluation,
      were eligible for inclusion. Quality was assessed with the use of the Consensus
      on Health Economic Criteria (CHEC)-list. Two-hundred-fifty-one studies were
      identified. Of these, 16 fitted our inclusion criteria. A study on enzyme
      replacement and substrate reduction therapies for lysosomal storage disorders did
      not perform a full economic evaluation due to the high drug costs and the lack of
      a measurable effect on either clinical or health-related quality of life
      outcomes. Likewise, a cost-effectiveness analysis of laronidase for
      mucopolysaccharidosis type 1 was considered unfeasible due to lack of clinical
      effectiveness data, while in the same study a crude model was used to estimate
      cost-utility of enzyme replacement therapy (ERT) for Fabry disease. Three
      additional studies, one on ERT for Fabry disease, one on ERT for Gaucher disease
      and one on eculizumab for paroxysmal nocturnal haemoglobinuria, used an approach
      that was too simplistic to lead to a realistic estimate of the incremental cost
      effectiveness (ICER) or cost-utility ratio (ICUR). In all other studies (N = 11)
      more sophisticated pharmacoeconomic models were used to estimate cost
      effectiveness and cost-utility of the specific drug, mostly ERT or drugs
      indicated for pulmonary arterial hypertension (PAH). Seven studies used a Markov
      state-transition model. Other models used were patient-level simulation models (N
      = 3) and decision trees (N = 1). Only 4 studies adopted a societal perspective.
      All but 2 studies discounted costs and effects appropriately. Drugs for metabolic
      diseases appeared to be significantly less cost-effective than drugs indicated
      for PAH, with ICERs ranging from ?43 532 (Gaucher disease) to ?3 282 252 (Fabry
      disease). Quality of studies using a Markov-state-transition or patient-level
      simulation model is in general good with 14-19 points on the CHEC-list. We
      therefore conclude that economic evaluations of ultra-orphan drugs are feasible
      if pharmacoeconomic modelling is used. Considering the need for modelling of
      several disease states and the small patient groups, a Markov-state-transition
      model seems to be most suitable type of model. However, it should be realised
      that ultra-orphan drugs will usually not meet the conventional criteria for cost
      effectiveness. Nevertheless, ultra-orphan drugs are often reimbursed. Further
      discussion on the use of economic evaluations and their consequences in case of
      ultra-orphan drugs is therefore warranted. 

PMID- 26223690
TI  - Psychosocial Outcomes of Participating in Pediatric Diabetes Camp.
AB  - OBJECTIVE: There are approximately 18,400 youth who are newly diagnosed with Type
      1 diabetes mellitus (T1DM) in the United States each year. Because of the
      potential for hypoglycemia, frequent need to monitor blood glucose, and other
      medical care associated with T1DM, children may not be able to participate in the
      typical summer camp experience. The aims of this study were (1) to evaluate the
      impact of camp on the child's attitude toward their illness, (2) to evaluate the
      child's confidence in self-care management of their diabetes, (3) to assess the
      child's perception and satisfaction with the camp experience, and (4) to evaluate
      the perception of camp experience by the parents. DESIGN AND SAMPLE: Thirty-eight
      parent-child dyads participated in a pretest, posttest quasi-experimental
      research study evaluating the benefits of a camping experience for the child with
      T1DM. RESULTS: Pre- and postcamp comparisons revealed improved attitude toward
      illness and improved self-efficacy after the camping experience. CONCLUSION:
      Results of the study support the psychosocial benefits of a camping experience
      for children with T1DM. Findings from the study can be used by health care
      providers as evidence to support the benefits of sending children with T1DM to
      residential summer camp.

PMID- 26223691
TI  - A Model based Survey of Colour Deconvolution in Diagnostic Brightfield
      Microscopy: Error Estimation and Spectral Consideration.
AB  - Colour deconvolution is a method used in diagnostic brightfield microscopy to
      transform colour images of multiple stained biological samples into images
      representing the stain concentrations. It is applied by decomposing the
      absorbance values of stain mixtures into absorbance values of single stains. The
      method assumes a linear relation between stain concentration and absorbance,
      which is only valid under monochromatic conditions. Diagnostic applications, in
      turn, are often performed under polychromatic conditions, for which an accurate
      deconvolution result cannot be achieved. To show this, we establish a
      mathematical model to calculate non-monochromatic absorbance values based on
      imaging equipment typically used in histology and use this simulated data as the
      ground truth to evaluate the accuracy of colour deconvolution. We show the non
      linear characteristics of the absorbance formation and demonstrate how it leads
      to significant deconvolution errors. In particular, our calculations reveal that
      polychromatic illumination causes 10-times higher deconvolution errors than
      sequential monochromatic LED illumination. In conclusion, our model can be used
      for a quantitative assessment of system components--and also to assess and
      compare colour deconvolution methods.

PMID- 26223692
TI  - Admission hypoxia-inducible factor 1alpha levels and in-hospital mortality in
      patients with acute decompensated heart failure.
AB  - BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a critical regulator for
      cellular oxygen balance. Myocardial hypoxia can induce the increased expression
      of HIF-1alpha. Our goals were to evaluate the value of HIF-1alpha in predicting
      death of patients with acute decompensated heart failure (ADHF) and describe the
      in vivo relationship between serum HIF-1alpha and N-terminal-pro-brain
      natriuretic peptide (NT-proBNP) levels. METHOD: We included 296 patients who were
      consecutively admitted to the emergency department for ADHF. The primary end
      point was in-hospital death. The patients were categorized as HFrEF (patients
      with reduced systolic function) and HFpEF (patients with preserved systolic
      function) groups. RESULTS: In our patients, the median admission HIF-1alpha level
      was 2.95 +/- 0.85 ng/ml. The HIF-1alpha level was elevated significantly in HFrEF
      patients and deceased patients compared with HFpEF patients and patients who
      survived. The HIF-1alpha level was positively correlated with NT-proBNP and
      cardiac troponin T levels, and negatively correlated with left ventricular
      ejection fraction and systolic blood pressure. Kaplan-Meier curves revealed a
      significant increase in in-hospital mortality in ADHF patients with higher HIF
      1alpha levels. Multivariable Cox regression analysis showed that HIF-1alpha
      levels were not correlated with the short-term prognosis of ADHF patients.
      CONCLUSIONS: This is the first study to evaluate the circulating levels of HIF
      1alpha in ADHF patients. Serum HIF-1alpha levels may reflect a serious state in
      patients with ADHF. Due to the limitations of the study, serum HIF-1alpha levels
      were not correlated with the in-hospital mortality based on regression analysis.
      Further studies are needed to demonstrate the diagnostic and/or prognostic role
      of HIF-1alpha as a risk biomarker in patients with ADHF.

PMID- 26223694
TI  - Incomplete Systemic Lupus Erythematosus: Early Diagnosis or Overdiagnosis?

PMID- 26223693
TI  - Significance of preoperative butyrylcholinesterase as an independent predictor of
      biochemical recurrence-free survival in patients with prostate cancer treated
      with radical prostatectomy.
AB  - BACKGROUND: Butyrylcholinesterase (BChE) is an alpha-glycoprotein found in the
      nervous system and liver. Its serum level is reduced in many clinical conditions,
      such as liver damage, inflammation, injury, infection, malnutrition, and
      malignant disease. In this study, we analyzed the potential prognostic
      significance of preoperative BChE levels in patients with prostate cancer (PCa)
      undergoing radical prostatectomy (RP). METHODS: We retrospectively evaluated 535
      patients with PCa who underwent RP from 1996-2014 at a single institution. Serum
      BChE was routinely measured in all patients before operation. Covariates included
      age, preoperative laboratory data [prostate-specific antigen (PSA), hemoglobin,
      total protein, albumin, BChE, lactate dehydrogenase, C-reactive protein],
      clinical T, biopsy Gleason score, D'Amico risk classification, and RP
      with/without neoadjuvant therapy. Univariate and multivariate analyses were
      performed to identify clinical factors associated with biochemical recurrence
      free survival (BRFS). Univariate analyses were performed using the Kaplan-Meier
      and log-rank methods, and multivariate analysis was performed using a Cox
      proportional hazard model. RESULTS: The median BChE level was 255 U/L (normal
      range 168-470 U/L). The median age of the enrolled patients was 68 years, and the
      median PSA level at diagnosis of PCa was 8.39 ng/mL. The median follow-up period
      was 65 months. The 5-year BRFS rate was 72.9 %. The 5-year BRFS rates in the BChE
      >= 168 and <= 167 U/L groups were 77.7 and 55.0 %, respectively (P < 0.001). In
      univariate analysis, BChE, cT, biopsy Gleason score, and D'Amico risk
      classification were significantly associated with BRFS. Multivariate analysis
      revealed that BChE was significantly associated with BRFS. CONCLUSIONS: This
      study validated preoperative serum BChE levels as an independent prognostic
      factor for PCa after RP.

PMID- 26223695
TI  - Biochemical nature of Russell Bodies.
AB  - Professional secretory cells produce and release abundant proteins. Particularly
      in case of mutations and/or insufficient chaperoning, these can aggregate and
      become toxic within or amongst cells. Immunoglobulins (Ig) are no exception. In
      the extracellular space, certain Ig-L chains form fibrils causing systemic
      amyloidosis. On the other hand, Ig variants lacking the first constant domain
      condense in dilated cisternae of the early secretory compartment, called Russell
      Bodies (RB), frequently observed in plasma cell dyscrasias, autoimmune diseases
      and chronic infections. RB biogenesis can be recapitulated in lymphoid and non
      lymphoid cells by expressing mutant Ig-MU, providing powerful models to
      investigate the pathophysiology of endoplasmic reticulum storage disorders. Here
      we analyze the aggregation propensity and the biochemical features of the intra-
      and extra-cellular Ig deposits in human cells, revealing beta-aggregated features
      for RB. 

PMID- 26223696
TI  - A Trial of Telephone Support Services to Prevent Further Intimate Partner
      Violence.
AB  - We conducted a randomized-controlled trial of telephone support services (TSS)
      versus enhanced usual care (EUC) for women who had reported intimate partner
      violence (IPV) within the past year during a visit to a pediatric emergency
      department. TSS nurse interventionists identified appropriate referrals to
      community programs, helped participants by problem-solving barriers to obtaining
      these local services, and provided social support. Three hundred women, ages 18
      years and above were recruited. The TSS and EUC groups did not differ on any
      outcome variable, including IPV victimization, feelings of chronic vulnerability
      to a perpetrator, depressive symptoms, and posttraumatic stress disorder
      symptoms. 

PMID- 26223697
TI  - Micellization properties of cardanol as a renewable co-surfactant.
AB  - With the aim to improve the features of surfactant solutions in terms of
      sustainability and renewability we propose the use of hydrogenated natural and
      sustainable plant-derived cardanol as an additive to commercial surfactants. In
      the present study we demonstrated that its addition, in amounts as high as 10%,
      to commercial surfactants of different charge does not significantly affect
      surfactant properties. Conversely, the presence of hydrogenated cardanol can
      strongly affect spectrophotometric determination of CMC if preferential
      interactions with the dyes used take place. This latter evidence may be
      profitably exploited in surfactant manufacturing by considering that the
      concurrent presence of a rigid organic molecule such as Orange OT and 10%
      hydrogenated cardanol decreases the CMC of CTAB up to 65 times. 

PMID- 26223698
TI  - Nutritional evaluation, antioxidant studies and quantification of poly phenolics,
      in Roscoea purpurea tubers.
AB  - BACKGROUND: Roscoea purpurea (Zingiberaceae) is commonly known as "kakoli".
      Traditionally, various parts like leaves, roots and flower etc. are used for the
      treatment of diabetic, hypertension, diarrhea, fever, inflammation etc. In Nepal
      tubers are boiled for edible purpose and also used in traditional veterinary
      medicine. The study aims for nutritional characterization, chemical profiling of
      R. purpurea (tubers) methanol extract (RPE) along with evaluation of its anti
      oxidant activity. Physicochemical and nutritional content were estimated as per
      standard protocols. Chemical profiling of markers includes method optimization,
      identification & quantification of bioactive poly phenolics through HPTLC. Anti
      oxidant potential RPE was analyzed via. Total phenolics (TPC), total flavonoids
      (TFC), reducing power assay, DPPH and beta-carotene bleaching model. RESULTS:
      Physicochemical and nutritional standards were established. Kaempferol (0.30%),
      vanillic acid (0.27%), protocatechuic (0.14%), syringic (0.80%) and ferulic acid
      (0.05%) were identified and then quantified. TPC and TFC content were found to be
      7.10 +/- 0.115 and 6.10 +/- 0.055%, reducing power of extract also increases
      linearly (r(2) = 0.946) with concentration, similar to standards. IC50 value of
      extract in DPPH and beta-carotene bleaching model was observed at 810.66 +/-
      1.154 and 600.66 +/- 1.154 ug/ml, which is significantly different from standards
      (p < 0.05). Although there is a positive, significant correlation between the
      phenolic and flavonoid content with anti oxidant activity of extract. CONCLUSION:
      Thus, study will authenticates the identity, utility of herb as nutrient
      supplement and an important medicinal plant having promising pharmacological
      activities for further elaborated/extended investigation work.

PMID- 26223699
TI  - Impact of real-time three-dimensional transesophageal echocardiography on
      procedural success for mitral valve repair.
AB  - BACKGROUND: For mitral valve repair, minimally invasive cardiac surgery as well
      as transcatheter valvular intervention have been developed. Under these
      conditions, three-dimensional transesophageal echocardiography (3D-TEE) plays a
      key role for planning the surgical treatment strategy. However, few data exist
      regarding the role of 3D-TEE in mitral valve repair. Therefore, we examined the
      impact of 3D-TEE on procedural success of mitral valve repair. METHODS AND
      RESULTS: We examined 86 consecutive patients who underwent mitral valve repair
      for degenerative mitral valve prolapse. Among them, 39 patients were examined by
      only two-dimensional transesophageal echocardiography (2D-TEE) and 47 patients
      underwent 3D-TEE in addition to 2D-TEE. The cardiac surgeons and physicians
      discussed the repair procedure preoperatively with the echocardiographic images.
      As a result, 18 patients of the 2D-TEE group and 37 patients of the 3D-TEE group
      underwent mitral valve repair by small thoracotomy including robotic approach.
      Simple repair was done in 21 with 2D-TEE and 21 with 3D-TEE and complex repair
      was done in 18 with 2D-TEE and 26 with 3D-TEE. Importantly, three patients with
      2D-TEE before surgery had to undergo reoperation due to recurrent severe mitral
      regurgitation with dehiscence of the annuloplasty rings, although none with 3D
      TEE did. CONCLUSIONS: These results demonstrate that 3D-TEE is helpful in
      assessing the morphology of mitral apparatus and complexity of mitral valve
      repair, particularly in minimally invasive cardiac surgery including robotic
      ones. We would suggest that sonographers, cardiologists, and cardiac surgeons
      should be familiar with 3D-TEE and work together throughout the perioperative
      period for better outcomes.

PMID- 26223701
TI  - Estimation of subject-specific ligament length variation during knee flexion.

PMID- 26223700
TI  - Why are people with dengue dying? A scoping review of determinants for dengue
      mortality.
AB  - BACKGROUND: Dengue is a viral disease whose clinical spectrum ranges from
      unapparent to severe forms and fatal outcomes. Although dengue death is 99%
      avoidable, every year around 20,000 deaths are estimated to occur in more than
      100 countries. We consider that, along with biological factors, social
      determinants of health (SDHs) are related to dengue deaths as well. METHODS: A
      scoping review was conducted to explore what has been written about the role of
      SDHs in dengue mortality. The inclusion criteria were that documents (grey or
      peer-reviewed) had to include information about dengue fatal cases in humans and
      be published between 1997 and 2013 and written in English, Spanish, Portuguese or
      French. The search was conducted using a set of key words related to dengue
      mortality in several electronic databases: PubMed, LILACS, COCHRANE, Scielo,
      Science Direct, WHOLIS, OpenGrey, OpenSingle and Google Scholar. Information on
      SDHs was categorized under individual, social and environmental, and health
      systems dimensions. A summative content analysis using QDA Miner was conducted to
      assess the frequency of information on SDHs and its contextual meaning in the
      reviewed literature. The role of each SDH in dengue mortality was assessed using
      content analysis results. RESULTS: From a total of 971 documents retrieved, 78
      met the criteria. Those documents were published in the Americas region (50.0%),
      Asia (38.4%), Europe (9.0%) and Africa (2.6%). The described SDHs related to
      dengue deaths included, in the individual dimension: age, ethnicity, education,
      type of infection and immunological status; and in the social dimension: poverty
      and care-seeking behavior. The health systems dimension included access,
      opportunity, and quality of care, as well as health staff knowledge. Ethnicity
      was considered a determinant that depends on cultural and socioeconomic
      conditions. CONCLUSIONS: Along with biological factors, there are several SDHs
      related to dengue mortality. However, only a few of these have been
      systematically analyzed, suggesting the need for more studies on this subject to
      inform the design and implementation of sustainable interventions to decrease
      dengue mortality. These findings nevertheless provide a better understanding of
      the non-biological factors involved in dengue mortality.

PMID- 26223702
TI  - Transparent Electrodes Printed with Nanocrystal Inks for Flexible Smart Devices.
AB  - Transparent electrodes (TEs) are crucial in a wide range of modern electronic and
      optoelectronic devices. However, traditional TEs cannot meet the requirements of
      smart devices under development in unique fields, such as electronic skins,
      wearable electronics, robotic skins, flexible and stretchable displays, and solar
      cells. Emerging TEs printed with nanocrystal (NC) inks are inexpensive and
      compatible with solution processes, and have huge potential in flexible,
      stretchable, and wearable devices. Every development in ink-based electrodes
      makes them more competitive for practical applications in various smart devices.
      Herein, we provide an overview of emergent ink-based electrodes, such as
      transparent conducting oxides, metal nanowires, graphene, and carbon nanotubes,
      and their application in solution-based flexible and stretchable devices. 

PMID- 26223703
TI  - Sexual scripting of heterosexual penile-anal intercourse amongst participants in
      an HIV prevention trial in South Africa, Uganda and Zimbabwe.
AB  - Sexual risk-taking is influenced by individual, interpersonal and social factors.
      This paper presents findings from a qualitative follow-up study to a clinical
      trial evaluating biomedical HIV prevention products among African women, explored
      participants' perceptions and experiences of heterosexual penile-anal
      intercourse, as well as the gendered power dynamics and relationship contexts in
      which this sexual behaviour occurs. In-depth interviews were conducted with 88
      women from South Africa, Uganda and Zimbabwe. Findings reveal that despite its
      social stigmatisation, women engage in penile-anal intercourse for reasons
      including male pleasure, relationship security, hiding infidelity, menstruation,
      vaginal infections, money and beliefs that it will prevent HIV transmission. In
      addition, participants described experiences of non-consensual penile-anal
      intercourse. We used sexual scripting theory as an analytical framework with
      which to describe the sociocultural and relationship contexts and gendered power
      dynamics in which these practices occur. These data on the distinct individual,
      dyadic and social contexts of heterosexual penile-anal intercourse, and the
      specific factors that may contribute to women's HIV risk, make a unique
      contribution to our understanding of heterosexual behaviour in these sub-Saharan
      countries, thereby helping to inform both current and future HIV prevention
      efforts for women in the region. 

PMID- 26223704
TI  - Insurance company denial of payment and enforced changes in the type and dose of
      opioid analgesics for patients with cancer pain.
AB  - Opioids are the mainstay of treatment for moderate to severe cancer pain. The
      variations in average monthly cost can make it difficult for most patients to
      procure them without adequate insurance coverage. There are increasing numbers of
      denials of payment and statements made by insurance agents and other sources
      regarding inappropriate opioid use, resulting in severe pain and emotional
      distress for cancer patients and their families. This case series describes five
      events where the insurer was a major barrier to opioid access. 

PMID- 26223705
TI  - Making the most out of life: Exploring the contribution of attention restorative
      theory in developing a non-pharmacological intervention for fatigue--ERRATUM.

PMID- 26223706
TI  - Up-regulation of lymphocyte antigen 6 complex expression in side-population cells
      derived from a human trophoblast cell line HTR-8/SVneo.
AB  - The continual proliferation and differentiation of trophoblasts are critical for
      the maintenance of pregnancy. It is well known that the tissue stem cells are
      associated with the development of tissues and pathologies. It has been
      demonstrated that side-population (SP) cells identified by fluorescence-activated
      cell sorting (FACS) are enriched with stem cells. The SP cells in HTR-8/SVneo
      cells derived from human primary trophoblast cells were isolated by FACS. HTR
      8/SVneo-SP cell cultures generated both SP and non-SP (NSP) subpopulations. In
      contrast, NSP cell cultures produced NSP cells and failed to produce SP cells.
      These SP cells showed self-renewal capability by serial colony-forming assay.
      Microarray expression analysis using a set of HTR-8/SVneo-SP and -NSP cells
      revealed that SP cells overexpressed several stemness genes including caudal type
      homeobox2 (CDX2) and bone morphogenic proteins (BMPs), and lymphocyte antigen 6
      complex locus D (LY6D) gene was the most highly up-regulated in HTR-8/SVneo-SP
      cells. LY6D gene reduced its expression in the course of a 7-day cultivation in
      differentiation medium. SP cells tended to reduce its fraction by treatment of
      LY6D siRNA indicating that LY6D had potential to maintain cell proliferation of
      HTR-8/SVneo-SP cells. On ontology analysis, epithelial-mesenchymal transition
      (EMT) pathway was involved in the up-regulated genes on microarray analysis. HTR
      SVneo-SP cells showed enhanced migration. This is the first report that LY6D was
      important for the maintenance of HTR-8/SVneo-SP cells. EMT was associated with
      the phenotype of these SP cells. 

PMID- 26223707
TI  - Assessment of pancreatic adenocarcinoma: Use of low-dose whole pancreatic CT
      perfusion and individualized dual-energy CT scanning.
AB  - INTRODUCTION: The objective of this study was to investigate the value of low
      dose whole pancreatic computed tomography (CT) perfusion integrated with
      individualized dual-energy CT (DECT) scanning in the diagnosis of pancreatic
      adenocarcinoma. METHODS: Twenty patients with pancreatic adenocarcinoma underwent
      pancreatic CT perfusion as well as individualized dual-phase DECT pancreatic
      scans. Perfusion characteristics of non-tumourous pancreatic parenchyma and
      pancreatic adenocarcinoma were analysed. Weighted-average 120 kVp images and the
      optimal monoenergetic images in dual phase were reconstructed and the contrast
      noise ratio (CNR) of pancreas-to-tumour were compared. RESULTS: There were
      significant difference on blood flow as well as blood volume between pancreatic
      adenocarcinoma and the non-tumourous pancreatic parenchyma (P < 0.05), whereas no
      difference on permeability (P > 0.05). CNRs of pancreas-to-tumour in
      individualized pancreatic phase were significantly higher than those in venous
      phase (P < 0.05), and CNRs of optimal monoenergetic images were higher than those
      on weighted-average 120 kVp images (P < 0.05) in both phase. Total effective
      radiation dose of CT examination was around 9.32-13.75 mSv. CONCLUSIONS: Low-dose
      whole pancreatic CT perfusion can provide functional information, and the
      individualized pancreatic phase DECT scan is the optimal method for detecting
      pancreatic adenocarcinomas. The integration of the two techniques has great value
      in clinical application.

PMID- 26223708
TI  - Successful treatment with 4-phenylbutyrate in a patient with benign recurrent
      intrahepatic cholestasis type 2 refractory to biliary drainage and bilirubin
      absorption.
AB  - AIM: Benign recurrent intrahepatic cholestasis type 2 (BRIC2) is caused by
      mutations in ABCB11, a gene encoding the bile salt export pump (BSEP) that
      mediates biliary bile salt secretion, and presents with repeated intermittent
      cholestasis with refractory itching. Currently, no effective medical therapy has
      been established. We previously provided experimental and clinical evidence
      suggesting the therapeutic potential of 4-phenylbutyrate (4PB) for the
      cholestatic attacks of BRIC2. METHODS: After examining the potential therapeutic
      use of 4PB treatment by in vitro studies, a patient with BRIC2 was treated p.o.
      with 4PB at gradually increasing doses (200, 350, and 500 mg/kg per day) for 4
      months. Biochemical, histological and clinical data were collected. RESULTS: The
      patient was diagnosed with BRIC2 because he had non-synonymous mutations
      (c.1211A>G [p.D404G] and 1331T>C [p.V444A]) in ABCB11, reduced hepatocanalicular
      expression of BSEP and low biliary bile salt concentrations. In vitro analysis
      showed that 4PB treatment partially restored the decreased expression of BSEP
      caused by p.D404G mutation. During the first 2 months of 4PB therapy at 200 and
      350 mg/kg per day, the patient had no relief from his symptoms. No beneficial
      effect was observed after additional treatment with bilirubin absorption and
      endoscopic nasobiliary drainage. However, after starting treatment at a dose of
      500 mg/kg per day, the patient's liver function tests and intractable itching
      were markedly improved. No apparent side-effects were observed during or after
      4PB therapy. The symptoms relapsed within 1.5 months after cessation of 4PB
      therapy. CONCLUSION: 4PB therapy would have a therapeutic effect on the
      cholestatic attacks of BRIC2.

PMID- 26223709
TI  - The Potential Protective Effects of 2-aminoethyl Diphenylborinate against Inner
      Ear Acoustic Trauma: Experimental Study Using Transmission and Scanning Electron
      Microscopy.
AB  - OBJECTIVE: In this prospective experimental study, we investigated the preventive
      effects of 2-aminoethyl diphenylborinate (2-APB) in rats exposed to acoustic
      trauma (AT). Light microscopic, transmission electron microscopic (TEM), and
      scanning electron microscopic (SEM) examinations were performed. MATERIALS AND
      METHODS: Eighteen healthy Wistar albino rats were divided into the following
      three groups: groups 1 (control), 2 (AT), and 3 (AT+APB). The rats in groups 2
      and 3 were exposed to AT; in group 3 rats, 2-APB at 2 mg/kg was also
      administered, initially transperitoneally, after 10 min. RESULTS: During the
      light microscopic, TEM, and SEM examinations, the structures of the cochlear hair
      cells, stereocilia, and Deiter's cells were normal in the control group. In the
      AT group, the organ of Corti and proximate structures were damaged according to
      the light microscopic examination. During the TEM examination, intense cellular
      damage and stereocilia loss were detected, while during the SEM examination,
      extensive damage and stereocilia loss were observed. Decreased damage with
      preserved cochlear structure was detected during the light microscopic
      examination in the AT+APB group than in the AT group. During the TEM and SEM
      examinations, although stereocilia loss occurred in the AT+APB group, near-normal
      cell, cilia, and tectorial membrane structures were also observed in the AT+APB
      group compared with the AT group. CONCLUSION: 2-APB may have protective effects
      against AT damage of the cochlea. The main mechanism underlying this effect is
      the inhibition of the vasoconstriction of the cochlear spiral modiolar artery,
      thereby improving cochlear blood flow. We conclude that 2-APB may also be
      effective if used immediately following AT.

PMID- 26223710
TI  - Evaluation of the Effect of Betahistine on Noise-Induced Hearing Loss Using
      Distortion Product Otoacoustic Emission and Scanning Electron Microscopy.
AB  - OBJECTIVE: To evaluate the protective effect of betahistine on noise-induced
      hearing loss (NIHL) using scanning electron microscopy (SEM) and distortion
      product otoacoustic emission (DPOAE). MATERIALS AND METHODS: A total of 8 adult
      albino guinea pigs were used in this study (study group: n=4 and control group:
      n=4). DPOAE measurements of both groups were performed before the procedure. Two
      hours before noise exposure, 0.9% NaCl solution was injected perorally to the
      control group and betahistine was administered through a peroral catheter to the
      study group. Both groups were then exposed to 105-dB sound pressure level (SPL) 4
      kHz frequency-based narrow-band noise for 2 h per day for 5 days. DPOAE
      measurements were performed again on the 6th day and cochleae were dissected and
      examined by SEM on the 7(th) day. RESULTS: Regarding the results of DPOAE, NIHL
      was observed in both groups on the 6th day (p<0.05). Loss, flattening, and
      fusion, which are findings of permanent hearing loss, were determined in the
      stereocilia of the inner and outer hair cells by SEM. These findings were
      evaluated as signs of permanent increase in the threshold. When DPOAE
      measurements and SEM results were evaluated in the study group, no significant
      difference was observed in NIHL compared with the control group (p>0.05).
      CONCLUSION: In our study, it was observed that simultaneous administration of
      betahistine during noise had no protective effect on permanent increase in the
      threshold. However, further studies on noise and long-term use of betahistine can
      be performed.

PMID- 26223711
TI  - N-acetylcysteine Prevents Gentamicin Ototoxicity in a Rat Model.
AB  - OBJECTIVE: The possible preventive effect of N-acetylcysteine (NAC) in gentamicin
      ototoxicity was studied with auditory brain stem responses (ABRs), otoacoustic
      emissions (OAEs), and histopathological investigation of the cochlea. MATERIALS
      AND METHODS: This study is conducted on 36 rats in three groups. Gentamicin,
      gentamicin plus NAC, and NAC alone were intraperitoneally administered for 15
      days. The rats were sacrificed to study the cochleas after testing hearing
      levels. RESULTS: ABR thresholds and OAEs were attenuated in the gentamicin group,
      in which apoptosis was detected with histopathological investigation. The group
      that received NAC in addition to gentamicin had better ABR thresholds and better
      OAEs. The histopathological evidence of apoptosis in was considerably less in
      this group. CONCLUSION: Gentamicin ototoxicity can be detected by ABR and OAE
      testing in rats, and NAC may protect the cochlear cells from apoptosis.

PMID- 26223712
TI  - Apoptotic Effects of Sanguinarine on the Organ of Corti 1 Cells: Comparison with
      Cisplatin.
AB  - OBJECTIVE: Sanguinarine is an alkaloid obtained from the root of Sanguinaria
      canadensis and other plants from the Papaveraceae family and is well known to
      possess a broad range of biological functions, such as antimicrobial, antifungal,
      anti-inflammatory, and antineoplastic activities. We aimed to specify the in
      vitro effect of sanguinarine on the House Ear Institute-Organ of Corti 1 (HEI
      OC1) cells and to compare this effect with the ototoxic effect of cisplatin
      (CDDP). MATERIALS AND METHODS: We performed cell proliferation assay for
      determining the in vitro effect of sanguinarine alone and compared it with the
      effect of cisplatin. Flow cytometry annexin-V apoptosis detection was performed.
      RESULTS: We found that sanguinarine and CDDP inhibited the cell growth in a dose
      dependant manner in HEI-OC1 cells after 24 h of incubation. In sanguinarine
      treated group, apoptosis was 6.6%, necrosis was 26.7%, and the cell viability was
      66.7%. Further, in CDDP-treated group, apoptosis was 5.6%, necrosis was 45.4%,
      and the cell viability was 48.7%. According to the annexin-V apoptosis detection
      results, we found that sanguinarine caused 3.9% apoptosis and 1.3% necrosis,
      while CDDP caused 2.9% apoptosis and 20% necrosis on HEI-OC1 cells. CONCLUSION:
      Our findings suggested that lower doses of sanguinarine are promising
      antineoplastic agents, which did not indicate any toxic effect on HEI-OC1 cells.
      Application of these data to clinical practice requires further support by in
      vivo studies.

PMID- 26223713
TI  - Effect of Growth Factor Supplementation on the Hair Cell Specific Markers of
      Cells Harvested from Basilar Membrane.
AB  - OBJECTIVE: Loss of auditory hair cells is a major cause of deafness. The presence
      of auditory progenitor cells in the inner ear raises the hope for mammalian inner
      ear cell regeneration. In this study, we aimed to investigate the effect of
      growth factor supplementations, namely a combination of epidermal growth factor
      (EGF), insulin-like growth factor (IGF), and beta (beta)-fibroblast growth factor
      (betaFGF), on the expression of hair cell-specific markers by cells harvested
      from the cochlear membrane. This would provide an insight into the capability of
      these cells to differentiate into hair cells. MATERIALS AND METHODS: EGF, IGF,
      and betaFGF were supplemented into the culture medium. The cells were evaluated
      by morphology, growth kinetic, gene expression, and protein expression. RESULTS:
      The cultured cells of mouse basilar membrane were spindle shaped. Growth factors
      enriched medium promotes a significantly higher proliferative activity than the
      basic culture medium but did not alter the cell morphology. Growth factors
      enriched medium did not show any significant differences in the protein
      expression of the hair cell-specific markers myosin VIIa and calretinin and the
      stem-cell marker nestin. Gene expression analysis showed that the expression of
      the hair cell-specific genes myosin VIIa and calretinin as well as the stem cell
      genes nestin, Rex1, and Sox2 was reduced after the cells were passaged in the
      growth factor-supplemented medium. Cells in the basic medium expressed a
      significantly higher level of hair cell-specific genes at certain passages.
      CONCLUSION: Growth factor supplementation could not maintain the expression of
      hair cell-specific markers by cells obtained from the cochlear membrane.

PMID- 26223714
TI  - Association between Family History and Idiopathic Sudden Sensorineural Hearing
      Loss.
AB  - OBJECTIVE: Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss
      of at least 30 dB occurring within three days over at least three contiguous
      frequencies. The etiology of SSNHL cannot always be precisely determined; in such
      cases, this condition is termed idiopathic SSNHL (ISSNHL). This unique study
      investigates the relationship between ISSNHL and positive family history for
      ISSNHL. MATERIALS AND METHODS: In total, 125 patients diagnosed with ISSNHL were
      retrospectively reviewed. The presence of ISSNHL in the family medical history
      and degree of kinship of family members diagnosed with ISSNHL were determined.
      For univariate analysis, a chi-squared test and/or Fisher's exact test was used
      for between-group comparisons of qualitative variables; a t-test was used for
      quantitative variables. Significant variables in the univariate analysis were
      introduced into stepwise logistic regression for multivariate analysis. P<0.05
      indicated statistical significance. RESULTS: Fifty-nine (47.2%) patients were
      male and 66 (52.8%) were female. Statistical analysis revealed no significant
      difference between sex and development of ISSNHL (p=0.04). Forty-two (33.6%)
      patients had a family medical history of ISSNHL, whereas 83 (66.4%) did not. A
      statistically significant association between the development of ISSNHL and a
      family history of ISSNHL was observed (p<0.05). CONCLUSION: Our study supports an
      association between ISSNHL and genetic predisposition. Proving genetic
      susceptibility to ISSNHL will lead to improvements in the prediction, early
      diagnosis, and treatment of this disease.

PMID- 26223715
TI  - Comparison of Tone Burst, Click and Chirp Stimulation in Vestibular Evoked
      Myogenic Potential Testing in Healthy People.
AB  - OBJECTIVE: Vestibular evoked myogenic potential (VEMP) is a clinical test used in
      the diagnosis of vestibular diseases. VEMP uses several stimulants to stimulate
      the vestibular system and measure myogenic potentials. The aim of this study was
      to compare the effects of tone burst, click, and chirp stimulation in VEMP on the
      latency and amplitude of myogenic potentials. MATERIALS AND METHODS: We compared
      the results of 78 ears from 39 volunteers. We measured the sternocleidomastoid
      muscle potential of each ear following a 500-Hz tone burst, click, and chirp
      stimulation while in a sitting position and evaluated the latency and amplitude.
      RESULTS: The tone burst stimulus resulted in waves with longer latency (15.8+/
      1.9 ms) but higher amplitude (35.9+/-17.1 uV) compared with the other stimuli,
      and the chirp stimulus resulted in waves with shorter latency (9.9+/-2.4 ms) but
      lower amplitude (33+/-18.6 uV) (p<0.001). The VEMP asymmetry ratio did not
      significantly differ. ONCLUSION: Because the amplitudes and latencies of
      different stimuli significantly differ, further studies including more patients
      and stimulus types are needed to obtain standardized VEMP protocols.

PMID- 26223716
TI  - Automatic Pre-Attentive Auditory Responses: MMN to Tone Burst Frequency Changes
      in Autistic School-Age Children.
AB  - OBJECTIVE: Autism is a pervasive developmental disorder that includes deficits in
      socialization, communication, and adaptive functioning. The mismatch negativity
      (MMN) is a component of evoked response potentials that reflects pre-attentive
      change detection. The purpose of this study was to determine whether a group of
      autistic school-age children had abnormal changes in auditory MMN and to analyze
      and compare the results with an age-matched group of normal children. MATERIALS
      AND METHODS: This prospective study was carried out on 31 autistic school-age
      children. Thirty age-, gender-, and IQ-matched children served as a control
      group. The children were evaluated through diagnostic procedures that included
      psychometric and speech language tests and audiological assessments. Auditory
      MMNs were recorded from all participants, and the peak amplitudes and latencies
      were measured. RESULTS: The mean ages were 11.3+/-2.8 and 11.2+/-3.2 years for
      the autistic and normal children, respectively. The MMN amplitudes obtained from
      the two groups were found to be statistically significantly different. The MMN
      amplitudes were reduced, and latencies were prolonged in autistic versus normal
      children. CONCLUSION: Our results suggest that children with autism do have
      auditory changes at the level measured by MMN, mainly pre-attentive response,
      which argues for a doubt on affection of the supposed origin of auditory MMN in
      those children.

PMID- 26223717
TI  - What Is the Audiological Evaluation Time for those Aged 0-5 Years and Older?
AB  - OBJECTIVE: The purpose of this study was to determine the time taken to perform
      audiological evaluation under routine clinical test conditions. We also aimed to
      investigate relevant variables and reasons for increases in test time. MATERIALS
      AND METHODS: The total test times of 300 patients were recorded and calculated
      using an "Audiological Evaluation Time Calculation Form." Behavioral and
      objective test times were determined and calculated separately. The patients were
      divided into groups on the basis of age, educational status, cooperation, and
      coordination in order to determine the effects of these factors on the test time.
      RESULTS: The mean time for behavioral tests was 41.85 min for children below the
      age of 6 years and 36.2 min for those above that age. The times for transient
      evoked otoacoustic emission, distortion product otoacoustic emission, automated
      auditory brainstem response, and auditory brainstem response tests were 6.4/4.3
      min, 4.8/6.9 min, 14.4 min, and 48.0/47.5 min, respectively, for the two age
      groups. The shortest total test times were obtained from the 15-29 age group,
      high school/university levels, and patients who cooperated. Conversely, the
      longest total test times were found in 6-14 age group, those with no literacy,
      and who hardly cooperated. CONCLUSION: Although audiological evaluation methods
      have well-defined international standards, numerous factors, including patient
      conditions, clinician experience, and equipment, may have an adverse effect on
      test times. Determining the optimum patient number in one working day can help
      reduce workload and work stress and prevent possible errors of
      diagnosis/treatment. It will also help determine staff numbers needed in
      audiology clinics.

PMID- 26223718
TI  - The Impact of Systemic and Local Administration of Ascorbic Acid on Traumatic
      Perforation of Tympanic Membrane and Myringosclerosis.
AB  - OBJECTIVE: In the present study, tympanic membranes (TM) harvested from
      myringotomized rats were analyzed histopathologically to compare the systemic and
      local effects of ascorbic acid on the development of myringosclerosis. MATERIALS
      AND METHODS: Forty male Wistar-Albino rats weighing between 350-400 g were
      included in this study. Under otomicroscopic examination, a standard 2-mm
      myringotomy incision was made on the posteroinferior quadrant of the TM of both
      ears. Rats were randomized into five groups as control, topical ascorbic acid 50
      mg/kg, systemic ascorbic acid 50, 100, and 200 mg/kg groups, each group
      containing eight rats. On the 15th day of the study, the rats were decapitated,
      and bullas of the rats were extracted. Sections were stained with hematoxylin
      eosin and examined through light microscopy. Inflammation, distribution width of
      plaques, edema, and neovascularization were observed on the lamina propria.
      Thickness of the TM was evaluated under the microscope and scored
      semiquantitatively. RESULTS: When intergroup comparisons of parameters related to
      total TM thickness were performed, differences between the control group and
      topical AA (ascorbic acid) or systemic treatment groups were found to be
      statistically significant (p<0.005). A statistically significant difference was
      detected among control, topical and systemic 200 mg/kg ascorbic acid groups for
      the edematous lamina propria (p=0.003 and p<0.05, respectively). CONCLUSION: For
      the total TM thickness, systemic and topical ascorbic acid use was effective when
      compared with the control group. It has been concluded that systemic use of
      higher doses of (200 mg/kg) ascorbic acid is beneficial in the resolution of the
      edematous lamina propria.

PMID- 26223719
TI  - Value of Echo-Planar Diffusion-Weighted Magnetic Resonance Imaging for Detecting
      Tympanomastoid Cholesteatoma.
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of echo
      planar diffusion-weighted magnetic resonance imaging (EP-DWI) and high-resolution
      computed tomography (HRCT) in the detection and localization of cholesteatoma.
      MATERIALS AND METHODS: Fifty-four patients were prospectively included in this
      study. Patients with suspected primary or residual cholesteatoma were evaluated
      by EP-DWI and HRCT before tympanomastoid surgery. Radiological findings were
      correlated with intraoperative findings. RESULTS: EP-DWI and HRCT accurately
      predicted the presence or absence of cholesteatoma in 49 of 54 (90.7%) and 37 of
      54 (68.5%) patients, respectively. The sensitivity, specificity, and positive and
      negative predictive values of EP-DWI were 88.4%, 92.8%, 92%, and 89.6%,
      respectively. However, sensitivity, specificity, and positive and negative
      predictive values of HRCT were 69%, 67.8%, 66.6%, and 73.07%, respectively.
      CONCLUSION: This study demonstrates that EP-DWI is more reliable in predicting
      the presence and localization of cholesteatoma compared with HRCT, before
      tympanomastoid surgery.

PMID- 26223720
TI  - Does Diffusion-Weighted MR Imaging Change the Follow-Up Strategy in Cases with
      Residual Cholesteatoma?
AB  - OBJECTIVE: To analyze the effectiveness of diffusion-weighted magnetic resonance
      imaging (DW-MRI) in the evaluation of recurrent cholesteatomas. MATERIALS AND
      METHODS: Twenty-three patients undergoing second-look surgery were included in
      our study. There were 14 men and 9 women with ages ranging from 10 to 50. All
      patients underwent DW-MRI prior to second-look surgery. All magnetic resonance
      imaging (MRI) examinations were performed with a 1.5-T MRI unit using a standard
      8-channel neurovascular coil. DW-MRI and apparent diffusion coefficient maps were
      included in the examination. Cholesteatoma was diagnosed on the DW-MRI as a
      marked hyperintense signal in comparison with brain tissue. All cases were
      classified as positive or negative. RESULTS: The sensitivity and specificity of
      DW-MRI were 86% and 87%, respectively. The positive predictive value of DW-MRI
      was 92%, while the negative predictive value was 77%. CONCLUSION: The DW-MRI
      technique is an important and effective technique in the evaluation of residual
      cholesteatoma. It can be an alternative method to second-look surgery, which can
      spare patients repeat operations.

PMID- 26223721
TI  - Is Middle Ear Pressure Effected by Nasal Packings after Septoplasty?
AB  - OBJECTIVE: To investigate the effects of different types of nasal packings on
      middle ear pressure in patients undergoing septoplasty. MATERIALS AND METHODS:
      Sixty patients who were suffering from nasal obstruction and who had to undergo
      septoplasty because of nasal septal deviation were included in the study. After
      the septoplasty, Merocel packings and internal nasal splints were
      intraoperatively applied in thirty patients each. Middle ear pressure was
      evaluated by tympanometry. Tympanometric peak pressures were used for this aim.
      Acoustic impedance measurements were performed in both ears, and the average
      values of the two ears were calculated. Tympanometric measurements were performed
      for patients during the preoperative period and on the 2(nd) and 5(th)
      postoperative days. RESULTS: There were 30 (5 females, 25 males; average age 23
      years) patients in the internal nasal splint group and 30 (8 females, 22 males;
      average age 26 years) patients in the anterior Merocel packing group. When the
      values obtained by acoustic impedancemetry before the operation and on the
      postoperative 5(th) day were compared, there was no statistically significant
      difference between the groups. The middle ear pressure significantly decreased in
      the anterior Merocel packing group compared with that in the internal nasal
      splint group. The intragroup comparison of the acoustic impedance measurements of
      the internal nasal splint group revealed no significant difference between the
      preoperative acoustic impedance values and the values obtained on the
      postoperative 2(nd) day. CONCLUSION: Cannulated silicone intranasal splints are
      better in terms of patient comfort after an intranasal surgery without effecting
      eustachian tube function.

PMID- 26223722
TI  - Role of Laryngopharyngeal Reflux in the Pathogenesis of Otitis Media with
      Effusion.
AB  - OBJECTIVE: To determine whether there is an association between otitis media with
      effusion and laryngopharyngeal reflux in children. MATERIALS AND METHODS: This
      study included 31 children with otitis media with effusion. The pepsinogen level
      in the middle ear fluid of all patients was measured by sandwich enzyme-linked
      immunosorbent assay. Each patient's middle ear fluid was investigated for
      Helicobacter pylori (H. pylori) using the Campylobacter-like organism (CLO) test.
      The middle ear pepsinogen levels were compared with those in the serum. The
      correlation between pepsinogen levels and H. pylori positivity in the middle ear
      fluid was investigated. RESULTS: The mean middle ear pepsinogen level (211.69
      ng/mL) was significantly higher than that in the serum (24.18 ng/mL) in patients
      with otitis media with effusion. The middle ear aspirates of six patients (19%)
      were positive for H. pylori, and the correlation between H. pylori positivity and
      increased pepsinogen levels in the middle ear fluid was statistically significant
      in patients with otitis media with effusion. CONCLUSION: We detected higher
      pepsinogen levels and H. pylori positivity rates in the middle ear fluid than in
      the serum of patients with otitis media with effusion. These results support the
      role of laryngopharyngeal reflux in the pathogenesis of otitis media with
      effusion.

PMID- 26223723
TI  - Malignant Otitis Externa - A Retrospective Study of 15 Patients Treated in a
      Tertiary Healthcare Center.
AB  - OBJECTIVE: Malignant otitis externa (MOE) is an uncommon but potentially fatal
      disease of the external auditory canal. The study aimed at evaluating the
      demographic profile, coexisting disabilities, clinical presentations, and
      management of MOE. MATERIALS AND METHODS: This is a retrospective study of
      patients with MOE who were treated at the Otorhinolaryngology Department of our
      institution. The case records of patients treated between 2006 and 2013 for MOE
      were reviewed from the Medical Records Department of the hospital. The details
      were tabulated in a master chart, and the data were analyzed. RESULTS: Fifteen
      patients with MOE were treated as inpatients at the Otorhinolaryngology
      Department of our hospital during the study period. Of these, 12 were males and
      three were females. Among the 15 patients, 14 were diabetic and one was non
      diabetic. Earache was the most common symptom observed in all patients; edema and
      granulations in the ear canal was the most common sign observed in 12 patients.
      Pseudomonas aeruginosa was isolated in 11 patients. All patients were managed
      medically with intravenous antibiotics. CONCLUSION: MOE is a rare but aggressive
      condition affecting the external ear, which is commonly observed in elderly
      diabetic individuals. Immune senescence may be the cause of MOE in elderly
      people. Pseudomonas is the most common causative organism isolated in this
      condition. Most of these patients can be managed with medical treatment;
      reserving surgery only for the removal of granulation tissue and for
      histopathological examination.

PMID- 26223724
TI  - Temporal Bone Posterior Wall Defect, a New Clinic Entity?
AB  - OBJECTIVE: To define clinical and audiological findings in patients with temporal
      bone posterior wall defects (TBPWD) and to investigate possible relationships
      between these findings and the characteristics of the defect. MATERIALS AND
      METHODS: The computed tomography (CT) views of 1198 patients with
      vestibulocochlear symptoms between 2007 and 2012 were retrospectively evaluated,
      and TBPWD and associated anomalies were investigated. Patients who had TBPWD were
      called back, and clinical and audiological examinations (tympanometry, pure tone
      audiometry, acoustic reflexes, and otoacoustic emission) were performed. RESULTS:
      Twenty-eight (2.34%) patients had TBPWD. Twenty-three of them were eligible for
      the study. Size of the defect was significantly correlated with the presence of
      tinnitus and/or vertigo (p<0.005). The cut-off values for the largest size of
      TBPWD were 1.65 mm [sensitivity: 0.67 and specificity: 0.77 (95% CI: 0.58-0.97);
      p=0.04] in case of the presence of tinnitus and 1.85 for vertigo (sensitivity:
      0.78 and specificity: 0.86 (95% CI: 0.67-0.99); p=0.006). In pure tone audiometry
      tests, mixed-type hearing loss was present in four (17%) patients, sensorineural
      hearing loss was present in three (13%) patients, and conductive-type hearing
      loss was present only in one (4%) patient. Otoacoustic emission tests revealed
      significant differences in signal/noise ratios at frequencies of 500, 750, 1000,
      and 6000 Hz. CONCLUSION: For the first time in the literature, we defined
      clinical and audiological findings in patients with TBPWDs. These defects seem to
      cause more prevalent symptoms of vertigo and tinnitus and disturb the
      audiological characteristics of patients.

PMID- 26223725
TI  - Consensus-Based Recommendations on the Definition and Classification of
      Cholesteatoma.
AB  - Development of a consensus on the definitions and classification of cholesteatoma
      is essential for scientific community to exchange information on clinical studies
      and compare their outcomes. The aim of the study is to reach a consensus among
      members of the European Academy of Otology and Neurotology (EAONO) regarding the
      definitions and classification related to cholesteatoma. A set of statements was
      developed by the authors utilizing the literature on the definition and
      classification of cholesteatoma. A questionnaire was sent to the members of the
      EAONO, inviting them to state if they are in agreement with each of the
      statements and if not, then to provide comments or suggestions for revision.
      Responses were evaluated and modified using online questionnaire and survey
      software based on the Delphi technique, a cyclical process of gathering
      information, summarizing, and re-submitting the revised statements to the same
      target population until a consensus is reached. Target agreement among the
      responders was set at a minimum of 80%, and the cycle of revision and re
      submission of the statements were repeated until a consensus was reached on a
      majority of the statements. A steering group has been established to evaluate the
      results of the survey and worked via the process of cognitive debriefing. Out of
      364 EAONO members, 123 responded to the first consensus cycle, 77 to the second
      cycle, and 53 to the third cycle. After three cycles, all statements concerning
      cholesteatoma definitions reached the target of 80% consensus. However, a
      consensus on the classification of cholesteatoma could not be achieved. The
      steering group excluded four statements of cholesteatoma definition and
      established a consensus on cholesteatoma classification. A consensus on
      cholesteatoma definitions was reached among the members of the EAONO. The final
      revision on consensus statements for cholesteatoma definition and classification
      has been made via the process of cognitive debriefing of the steering group. 

PMID- 26223726
TI  - Giant Cell Tumor of Infratemporal Fossa and Mandibular Condyle: A Case Report.
AB  - Giant cell tumors (GCT) of the bone are uncommon primary bone neoplasms that
      occur mainly in the epiphyses of long bones. However, GCT with tumoral growth in
      the cranium is rarely encountered, particularly in the temporal bone. GCT
      demonstrates benign histological features but is locally aggressive, and surgical
      excision is the treatment of choice. The authors describe a 31-year-old man who
      presented with trismus and an extensive GCT, which originated in the petrous and
      squamous portions of the temporal bone and extended into the left mandibular
      ramus and middle ear. He was treated by en bloc resection of the tumor by left
      temporal craniectomy using an extended pterional approach and canal wall down
      mastoidectomy. In addition to the description of this unusual case of GCT of the
      temporal bone presenting with trismus, a review of the related literature is
      included. 

PMID- 26223727
TI  - Conchal Lipoma: A New Lipoma Site.
AB  - Lipomas, the most common benign tumors, rarely originate from the external ear.
      The first case of a lipoma originating from the concha of the auricle was
      reported and described in the current study. It was successfully removed under
      local anesthesia. This directs the attention of surgeons toward lipomas as a
      cause of conchal mass because the early diagnosis of a lipoma when it is still
      small allows its easy, safe, and complete removal. 

PMID- 26223728
TI  - Two Cases of Angioleiomyoma of the Auricle.
AB  - Angioleiomyoma is a benign tumor originating from the muscularis layer of blood
      vessel walls. It usually occurs in extremities, and the auricle is not a frequent
      site for the development of this tumor. We present two cases of auricular
      angioleiomyoma diagnosed after pathological examination along with a review of
      literature. 

PMID- 26223729
TI  - Letter to the Editor regarding article by Yucedag et al. "The Effects of
      Nonylphenol on Hearing in Rats".

PMID- 26223730
TI  - The untapped potential of a low cost evidence based smartphone application for
      smokeless tobacco cessation.

PMID- 26223732
TI  - Ibrutinib: from bench side to clinical implications.
AB  - The activation of the B cell receptor (BCR) is nowadays known to play a primary
      role in the etiopathogenesis of a multitude of B cell malignancies, being one of
      the main factors responsible for the enhanced proliferation and survival of
      transformed cells. Thanks to the characterization and continuous discovery of the
      pathways driving B cell proliferation in consequence to BCR activation, it has
      been possible to develop a small molecule inhibitor specifically antagonizing the
      Bruton's tyrosine kinase (BTK), an enzyme located in an early strategic position
      within the whole pathway. Ibrutinib, formerly PCI-32765, is a first in class,
      potent, specific, irreversible and relatively safe BTK inhibitor, demonstrating
      so far an impressive efficacy in the treatment of chronic lymphocytic leukemia,
      diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma (MCL),
      Waldenstrom macroglobulinemia and multiple myeloma. This review will summarize
      the most important pharmacological evidences available as of today and will take
      in consideration the latest findings regarding the mechanism of action of
      ibrutinib. 

PMID- 26223733
TI  - Erratum to: Technological Innovations for High-Throughput Approaches to In Vitro
      Allergy Diagnosis.

PMID- 26223734
TI  - A Multiscale Model of Cardiovascular System Including an Immersed Whole Heart in
      the Cases of Normal and Ventricular Septal Defect (VSD).
AB  - A mathematical and computational model combining the heart and circulatory system
      has been developed to understand the hemodynamics of circulation under normal
      conditions and ventricular septal defect (VSD). The immersed boundary method has
      been introduced to describe the interaction between the moving two-dimensional
      heart and intracardiac blood flow. The whole-heart model is governed by the
      Navier-Stokes system; this system is combined with a multi-compartment model of
      circulation using pressure-flow relations and the linearity of the discretized
      Navier-Stokes system. We investigate the velocity field, flowmeters, and pressure
      volume loop in both normal and VSD cases. Simulation results show qualitatively
      good agreements with others found in the literature. This model, combining the
      heart and circulation, is useful for understanding the complex, hemodynamic
      mechanisms involved in normal circulation and cardiac diseases. 

PMID- 26223735
TI  - Extension and Justification of Quasi-Steady-State Approximation for Reversible
      Bimolecular Binding.
AB  - The quasi-steady-state approximation (QSSA) is commonly applied in chemical
      kinetics without rigorous justification. We provide details of such a
      justification in the ubiquitous case of reversible two-step bimolecular binding
      in which molecules as an intermediate step of the reaction form a transient
      complex. First, we justify QSSA in the regime that agrees with the results in the
      literature and is characterized by max{R0, L0} ? K(m). Here, R0 and L0 are the
      initial concentrations of reacting receptor and ligand, respectively, and K(m) is
      the Michaelis constant. We also validate QSSA under an alternative condition that
      can be viewed as partially irreversible binding, and it does not require a tight
      bound on R0 and L0 but rather requires k2 + k-2 ? k-1. Here, k-1 is the rate
      constant of decomposition of the transient complex to the ligand and the
      receptor, and k2 and k-2 are the forward and the reverse rate constants of
      transformation of the complex to the product, respectively. Furthermore, we
      provide arguments that QSSA can also be accurate in a regime when max{R0, L0} ~
      K(m) and k2 + k-2 ~ k-1 if |R0 - L0| ? K(m). The derived conditions may be of
      practical use as they provide weaker requirements for the validity of QSSA
      compared to the existing results.

PMID- 26223736
TI  - In Situ Powder Diffraction Studies of Electrode Materials in Rechargeable
      Batteries.
AB  - The ability to directly track the charge carrier in a battery as it
      inserts/extracts from an electrode during charge/discharge provides unparalleled
      insight for researchers into the working mechanism of the device. This
      crystallographic-electrochemical information can be used to design new materials
      or modify electrochemical conditions to improve battery performance
      characteristics, such as lifetime. Critical to collecting operando data used to
      obtain such information in situ while a battery functions are X-ray and neutron
      diffractometers with sufficient spatial and temporal resolution to capture
      complex and subtle structural changes. The number of operando battery experiments
      has dramatically increased in recent years, particularly those involving neutron
      powder diffraction. Herein, the importance of structure-property relationships to
      understanding battery function, why in situ experimentation is critical to this,
      and the types of experiments and electrochemical cells required to obtain such
      information are described. For each battery type, selected research that
      showcases the power of in situ and operando diffraction experiments to understand
      battery function is highlighted and future opportunities for such experiments are
      discussed. The intention is to encourage researchers to use in situ and operando
      techniques and to provide a concise overview of this area of research.

PMID- 26223737
TI  - From para-Benziporphyrin to Rhodium(III) 21-Carbaporphyrins: Imprinting
      Rh???eta(2)-CC, Rh???eta(2)-CO, and Rh???eta(2)-CH Coordination Motifs.
AB  - Rhodium(III) para-benziporphyrin alters the fundamental reactivity of the built
      in para-phenylene moiety. Due to additional macrocyclic stabilization, a sequence
      of intramolecular rearrangements are triggered to afford rhodium(III) 21
      carbaporphyrin, which incorporates the rhodacyclopropane motif. The peculiar
      reversible transformations of the bridging methylene unit provide an example of
      selective and reversible aliphatic C-H bond elimination. Rhodium(III) 21
      carbaporphyrin can be oxygenated to rhodium(III) 21-oxy-21-carbaporphyrin,
      whereas the metal ion interacts with the C(21)-O(25) fragment in an eta(2)
      fashion. This species demonstrates a remarkable axial affinity toward alkenes.

PMID- 26223738
TI  - Lanthanide Luminescence Modulation by Cation-pi Interaction in a Bioinspired
      Scaffold: Selective Detection of Copper(I).
AB  - A prototype luminescent turn-on probe for Cu(+) (and Ag(+)) is described,
      harnessing a selective binding site (log Kass = 9.4 and 7.3 for Cu(+) and Ag(+),
      respectively) based on the coordinating environment of the bacterial metallo
      chaperone CusF, integrated with a terbium-ion-signaling moiety. Cation-pi
      interactions were shown to enhance tryptophan triplet population, which
      subsequently sensitized, on the microsecond timescale, the long-lived terbium
      emission, offering a novel approach in bioinspired chemosensor design.

PMID- 26223739
TI  - Quality assurance in radiology: peer review and peer feedback.
AB  - Peer review in radiology means an assessment of the accuracy of a report issued
      by another radiologist. Inevitably, this involves a judgement opinion from the
      reviewing radiologist. Peer feedback is the means by which any form of peer
      review is communicated back to the original author of the report. This article
      defines terms, discusses the current status, identifies problems, and provides
      some recommendations as to the way forward, concentrating upon the software
      requirements for efficient peer review and peer feedback of reported imaging
      studies. Radiologists undertake routine peer review in their everyday clinical
      practice, particularly when reporting and preparing for multidisciplinary team
      meetings. More formal peer review of reported imaging studies has been advocated
      as a quality assurance measure to promote good clinical practice. It is also a
      way of assessing the competency of reporting radiologists referred for
      investigation to bodies such as the General Medical Council (GMC). The literature
      shows, firstly, that there is a very wide reported range of discrepancy rates in
      many studies, which have used a variety of non-comparable methodologies; and
      secondly, that applying scoring systems in formal peer review is often
      meaningless, unhelpful, and can even be detrimental. There is currently a lack of
      electronic peer feedback system software on the market to inform radiologists of
      any review of their work that has occurred or to provide them with clinical
      outcome information on cases they have previously reported. Learning
      opportunities are therefore missed. Radiologists should actively engage with the
      medical informatics industry to design optimal peer review and feedback software
      with features to meet their needs. Such a system should be easy to use, be fully
      integrated with the radiological information and picture archiving systems used
      clinically, and contain a free-text comment box, without a numerical scoring
      system. It should form a temporary record that cannot be permanently archived. It
      must provide automated feedback to the original author. Peer feedback, as part of
      everyday reporting, should enhance daily learning for radiologists. Software
      requirements for everyday peer feedback differ from those needed for a formal
      peer review process, which might only be necessary in the setting of a formal GMC
      enquiry into a particular radiologist's reporting competence, for example. 

PMID- 26223740
TI  - The colour spectrum of lies.
AB  - In this reply to Ceci, Burd, and Helm, we discuss future directions for
      developmental research to (1) study the motivations underlying white lies and (2)
      how to classify lies that reflect other-regard and self-interest simultaneously. 

PMID- 26223742
TI  - EUROSPINE 2015 Copenhagen, Denmark, September 2-4 : ORAL PRESENTATIONS.

PMID- 26223741
TI  - Salvage surgery for recurrent oropharyngeal cancer: post-operative oncologic and
      functional outcomes.
AB  - CONCLUSION: Post-operative outcomes of salvage surgery for recurrent
      oropharyngeal squamous-cell carcinoma (OPSCC) were acceptable. Pathologic
      overall, T- or N-stage and patient comorbidities were the main predictors of
      patient clinical outcomes. OBJECTIVES: To evaluate post-operative outcomes of
      salvage surgery in patients with recurrent OPSCC and to determine their
      predictive factors. MATERIALS AND METHODS: This study retrospectively reviewed
      the electronic medical records of all patients who underwent salvage surgery for
      recurrent OPSCC, between 2000-2013, in our institution. Overall survival (OS) and
      cause-specific survival (SS) were determined by Kaplan-Meier analysis. Predictive
      factors of post-operative outcomes were investigated by using univariate and
      multivariate analyses. RESULTS: A total of 34 patients were included in this
      study. Local and general post-operative complication rates were 26% and 27%,
      respectively. A high level of comorbidity (Kaplan Feinstein Index: KFI >= 2) was
      the only factor associated with a higher risk of local (p = 0.03) and general (p
      = 0.04) complications. OS and SS rates at 3 years were 48% and 61%, respectively.
      In multivariate analysis, pathologic overall stage >= III was a significant
      predictor of OS (p = 0.02) and pathologic T-stage >= 3 was a significant
      predictor of SS (p = 0.01). Mean pre-operative and post-operative DOSS (dysphagia
      outcome and severity scale) scores were 4.4 and 3.9, respectively.

PMID- 26223743
TI  - A comparison of feasibility and safety of percutaneous fluoroscopic guided
      thoracic pedicle screws between Europeans and Asians: is there any difference?
AB  - PURPOSE: To directly compare the safety of fluoroscopic guided percutaneous
      thoracic pedicle screw placement between Caucasians and Asians. METHODS: This was
      a retrospective computerized tomography (CT) evaluation study of 880 fluoroscopic
      guided percutaneous pedicle screws. 440 screws were inserted in 73 European
      patients and 440 screws were inserted in 75 Asian patients. Screw perforations
      were classified into Grade 0: no violation; Grade 1: <2 mm perforation; Grade 2:
      2-4 mm perforation; and Grade 3: >4 mm perforation. For anterior perforations,
      the pedicle perforations were classified into Grade 0: no violation, Grade 1: <4
      mm perforation; Grade 2: 4-6 mm perforation; and Grade 3: >6 mm perforation.
      RESULTS: The inter-rater reliability was adequate with a kappa value of 0.83. The
      mean age of the study group was 58.3 +/- 15.6 years. The indications for surgery
      were tumor (70.3 %), infection (18.2 %), trauma (6.8 %), osteoporotic fracture
      (2.7 %) and degenerative diseases (2.0 %). The overall screw perforation rate was
      9.7 %, in Europeans 9.1 % and in Asians 10.2 % (p > 0.05). Grade 1 perforation
      rate was 8.4 %, Grade 2 was 1.2 % and Grade 3 was 0.1 % with no difference in the
      grade of perforations between Europeans and Asians (p > 0.05). The perforation
      rate was the highest in T1 (33.3 %), followed by T6 (14.5 %) and T4 (14.0 %).
      Majority of perforations occurred medially (43.5 %), followed by laterally (25.9
      %), and anteriorly (23.5 %). There was no statistical significant difference (p >
      0.05) in the perforation rates between right-sided pedicle screws and left-sided
      pedicle screws (R: 10.0 %, L: 9.3 %). CONCLUSIONS: There were no statistical
      significant differences in the overall perforation rates, grades of perforations,
      direction of perforations for implantation of percutaneous thoracic pedicle
      screws insertion using fluoroscopic guidance between Europeans and Asians. The
      safety profile for this technique was comparable to the current reported
      perforation rates for conventional open pedicle screw technique.

PMID- 26223744
TI  - Microendoscopic posterior decompression for the treatment of thoracic myelopathy
      caused by ossification of the ligamentum flavum: a technical report.
AB  - PURPOSE: Ossification of the ligamentum flavum (OLF) is a common cause of
      progressive thoracic myelopathy in East Asia. Good surgical results are expected
      for patients who already show myelopathy. Surgical decompression using a
      posterior approach is commonly used to treat OLF. This study investigated the use
      of microendoscopic posterior decompression for the treatment of thoracic OLF.
      METHODS: Microendoscopic posterior decompression was performed on 9 patients with
      myelopathy. Patients had a mean age of 59.8 years and single-level involvement,
      mostly at the T10-11 and T11-12 vertebrae. Computed tomography and magnetic
      resonance imaging were used to classify the OLF. A tubular retractor and
      endoscopic system were used for microendoscopic posterior decompression. Midline
      and unilateral paramedian approaches were performed in 2 and 7 patients,
      respectively. Intraoperative motor evoked potentials (MEPs) of 7 patients were
      monitored. Pre- and postoperative neurological status was evaluated using the
      modified Japanese Orthopaedic Association (mJOA) score. RESULTS: Thoracic OLF for
      all patients were classed as bilateral type with a round morphology. Improvement
      of MEPs at least one muscle area was recorded in all patients following posterior
      decompression. A dural tear in one patient was the only observed complication.
      The mean recovery rate was 44.9 %, as calculated from mJOA scores at a mean
      follow-up period of 20 months. CONCLUSIONS: Microendoscopic posterior
      decompression combined with MEP monitoring can be used to treat patients with
      thoracic OLF. The optimal surgical indication is OLF at a single vertebral level
      and of a unilateral or bilateral nature, without comma and tram track signs, and
      a round morphology.

PMID- 26223746
TI  - Advocacy.

PMID- 26223745
TI  - Comparison between Oxford Cobbmeter and digital Cobbmeter for measurement of Cobb
      angle in adolescent idiopathic scoliosis.
AB  - PURPOSE: The purpose of this study was to compare Cobb angle measurements
      performed using an Oxford Cobbmeter and digital Cobbmeter in a series of 20
      adolescent idiopathic scoliosis (AIS) patients. METHODS: Four observers measured
      major Cobb angles on 20 standing postero-anterior radiographs of AIS patients
      with both Oxford Cobbmeter and digital Cobbmeter (iPhone Cobbmeter Application).
      The measurements were repeated a week after the original measurements. RESULTS:
      The mean Cobb angle in this study was 43.6 degrees  +/- 23.62 degrees . The mean
      measurement time for an observer to measure the 20 Cobb angles was 24.9 min for
      the smart phone compared with 25.6 min for the Oxford Cobbmeter. The 95 %
      confidence interval for differences between smart phone and Oxford Cobbmeter
      measurements on the same radiograph was +/-3.68 degrees . The intra-observer
      variability of the smart phone is equivalent to the Oxford Cobbmeter. The 95 %
      confidence intervals for inter-observer error were +/-5 degrees  and +/-5.8
      degrees  for the smart phone and Oxford Cobbmeter, respectively. CONCLUSIONS: We
      conclude that the smart phone with integrated Tiltmeter and Cobbmeter application
      is an equivalent Cobb measurement tool to the Oxford Cobbmeter. The advantages of
      smart phone are the accuracy of determining the most inclined vertebrae and
      accordingly more precise Cobb angle measurement. The new smart phones with these
      integrated applications may be really helpful to the spine surgeons, especially
      in hospitals where PACS or Oxford Cobbmeter is not available.

PMID- 26223747
TI  - The respiratory examination.

PMID- 26223748
TI  - HeadCheck: A concussion app.

PMID- 26223750
TI  - Tahlia.

PMID- 26223751
TI  - A child found in extremis.

PMID- 26223752
TI  - The blood-stained nappy.

PMID- 26223759
TI  - Safety of melatonin.

PMID- 26223760
TI  - Benign cystic mesothelioma in a boy: An uncommon case mimicking a lymphangioma.

PMID- 26223761
TI  - Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths
      Involving Opioid and Benzodiazepine Combinations.
AB  - Effects of benzodiazepines on postmortem opioid parent and parent/metabolite
      blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone
      , or oxycodone-related accidental deaths. These opioids are partially metabolized
      by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam.
      Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl,
      hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent
      opioid concentrations were analyzed for 877 deaths. Parent/metabolite
      concentration ratios were analyzed for 349 deaths, excluding cases with co
      intoxicants present known to interfere with opioid elimination. Alprazolam in
      combination with diazepam significantly decreased median hydrocodone
      concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone
      parent/metabolite concentration ratio was reduced by 35% in the presence of
      diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not
      statistically significantly affect fentanyl or oxycodone concentrations. Possible
      factors affecting opioid concentrations and possible toxicity development,
      including any differential effects on specific opioids, should continue to be
      explored. 

PMID- 26223763
TI  - Erratum.

PMID- 26223762
TI  - Medium-Chain Acyl-CoA Dehydrogenase Deficiency in Adulthood: A Potential
      Diagnosis in a Patient with Mental Status Changes Suspected of Drug Toxicity.
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a rare but important
      component of the differential diagnosis for adults with a history of premortem
      mental status changes and the postmortem finding of hepatic steatosis. This case
      report describes a 30-year-old white man who, following a period of nausea and
      vomiting, was admitted to the hospital with sudden mental status deterioration
      followed rapidly by clinical deterioration and death. Treating physicians in this
      case suspected acute illicit drug toxicity with synthetic cathinones based on
      social history. Clinicians and medical examiners should be aware that the
      presentation, signs, and symptoms described may indicate an underlying inborn
      error of metabolism such as MCAD deficiency and take action accordingly. 

PMID- 26223764
TI  - Restoring normal eating behaviour in adolescents with anorexia nervosa: A video
      analysis of nursing interventions.
AB  - An important part of inpatient treatment for adolescents with anorexia nervosa is
      to restore normal eating behaviour. Health-care professionals play a significant
      role in this process, but little is known about their interventions during
      patients' meals. The purpose of the present study was to describe nursing
      interventions aimed at restoring normal eating behaviour in patients with
      anorexia nervosa. The main research question was: 'Which interventions aimed at
      restoring normal eating behaviour do health-care professionals in a specialist
      eating disorder centre use during meal times for adolescents diagnosed with
      anorexia nervosa? The present study was a qualitative, descriptive study that
      used video recordings made during mealtimes. Thematic data analysis was applied.
      Four categories of interventions emerged from the data: (i) monitoring and
      instructing; (ii) encouraging and motivating; (iii) supporting and understanding;
      and (iv) educating. The data revealed a directive attitude aimed at promoting
      behavioural change, but always in combination with empathy and understanding. In
      the first stage of clinical treatment, health-care professionals focus primarily
      on changing patients' eating behaviour. However, they also address the
      psychosocial needs that become visible in patients as they struggle to restore
      normal eating behaviour. The findings of the present study can be used to assist
      health-care professionals, and improve multidisciplinary guidelines and health
      care professionals' training programmes. 

PMID- 26223765
TI  - Physiological increases in lactate inhibit intracellular calcium transients,
      acidify myocytes and decrease force in term pregnant rat myometrium.
AB  - Lactate is increased in myometrial capillary blood from women in slow or non
      progressive labour (dystocia), suggesting that it is detrimental to uterine
      contractions. There are, however, no studies of the effect of lactate on the
      myometrium. We therefore investigated its effects and mechanism of action on
      myometrial strips from term pregnant rats. The effects on spontaneous and
      oxytocin-induced contractility in response to sodium lactate and other weak acids
      (1-20 mM) were studied. In some experiments, simultaneous force and intracellular
      Ca(2+) or pH (pH(i)) were measured with Indo-1 or Carboxy-SNARF, respectively.
      Statistical differences were tested using non-parametric tests. Lactate
      significantly decreased spontaneous contractility with an EC50 of 3.9 mM.
      Propionate, butyrate and pyruvate also reduced contractions with similar potency.
      The effects of lactate were reduced in the presence of oxytocin but remained
      significant. Lactate decreased pH(i) and nulling the decrease in pH(i) abolished
      its effects. We also show that lactate inhibited Ca(2+) transients, with these
      changes mirroring those produced on force. If Ca(2+) entry was enhanced by
      depolarization (high KCl) or applying the Ca(2+) channel agonist, Bay K 4644, the
      effects of lactate were abolished. Taken together, these data show that lactate
      in the physiological range potently decreases myometrial contractility as a
      result of its inhibition of Ca(2+) transients, which can be attributed to the
      induced acidification. The present study suggests that the accumulation of
      extracellular lactate will reduce myometrial contractions and could therefore
      contribute to labour dystocia.

PMID- 26223766
TI  - MStern Blotting-High Throughput Polyvinylidene Fluoride (PVDF) Membrane-Based
      Proteomic Sample Preparation for 96-Well Plates.
AB  - We describe a 96-well plate compatible membrane-based proteomic sample processing
      method, which enables the complete processing of 96 samples (or multiples
      thereof) within a single workday. This method uses a large-pore hydrophobic PVDF
      membrane that efficiently adsorbs proteins, resulting in fast liquid transfer
      through the membrane and significantly reduced sample processing times. Low
      liquid transfer speeds have prevented the useful 96-well plate implementation of
      FASP as a widely used membrane-based proteomic sample processing method. We
      validated our approach on whole-cell lysate and urine and cerebrospinal fluid as
      clinically relevant body fluids. Without compromising peptide and protein
      identification, our method uses a vacuum manifold and circumvents the need for
      digest desalting, making our processing method compatible with standard liquid
      handling robots. In summary, our new method maintains the strengths of FASP and
      simultaneously overcomes one of the major limitations of FASP without
      compromising protein identification and quantification. 

PMID- 26223767
TI  - Voltage-dependent anion channel (VDAC-1) is required for olfactory sensing in
      Caenorhabditis elegans.
AB  - The Ras-MAP kinase signaling pathway plays important roles for the olfactory
      reception in olfactory neurons in Caenorhabditis elegans. However, given the
      absence of phosphorylation targets of MAPK in the olfactory neurons, the
      mechanism by which this pathway regulates olfactory function is unknown. Here, we
      used proteomic screening to identify the mitochondrial voltage-dependent anion
      channel VDAC-1 as a candidate target molecule of MAPK in the olfactory system of
      C. elegans. We found that Amphid Wing "C" (AWC) olfactory neuron-specific
      knockdown of vdac-1 caused severe defects in chemotaxis toward AWC-sensed
      odorants. We generated a new vdac-1 mutant using the CRISPR-Cas9 system, with
      this mutant also showing decreased chemotaxis toward odorants. This defect was
      rescued by AWC-specific expression of vdac-1, indicating that functions of VDAC-1
      in AWC neurons are essential for normal olfactory reception in C. elegans. We
      observed that AWC-specific RNAi of vdac-1 reduced AWC calcium responses to
      odorant stimuli and caused a decrease in the quantity of mitochondria in the
      sensory cilia. Behavioral abnormalities in vdac-1 knockdown animals might
      therefore be due to reduction of AWC response, which might be caused by loss of
      mitochondria in the cilia. Here, we showed that the function of VDAC-1 is
      regulated by phosphorylation and identified Thr175 as the potential
      phosphorylation site of MAP kinase. 

PMID- 26223768
TI  - Immunological Analysis During Interferon-Free Therapy for Chronic Hepatitis C
      Virus Infection Reveals Modulation of the Natural Killer Cell Compartment.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection is a global health problem,
      resulting in liver failure, hepatocellular carcinoma, and liver-related death.
      Natural killer (NK) cells are innate immune cells, and their activity is known to
      correlate to viral treatment response of HCV. In this study, we investigate the
      immune effects of viral load decline with direct-acting antivirals (DAAs) in
      blood. METHODS: Twelve patients with chronic HCV were treated with asunaprevir
      and daclatasvir, and peripheral blood was analyzed at various time points during
      therapy. RESULTS: In line with previous studies, we confirmed restoration of HCV
      specific T-cell frequency upon viral load decline. In addition, we show that
      serum interferon (IFN)-gamma inducible-protein 10, interleukin (IL)-12p40, and IL
      18 levels decreased early after start of therapy. Surface expression of
      activation receptors NKp30, NKp46, and inhibitory receptor NKG2A on blood NK
      cells reduced during therapy. In addition, the expression of TRAIL on NK cells
      was reduced during IFN-free therapy, suggesting a decrease in TRAIL-mediated
      killing by NK cells. CONCLUSIONS: We show that viral load decline as a
      consequence of treatment with novel DAAs in chronic HCV patients reduces serum
      levels of NK cell-stimulating cytokines and causes correction of the altered NK
      cell phenotype observed in chronic HCV patients. CLINICAL TRIALS REGISTRATION:
      NCT02282709.

PMID- 26223769
TI  - Enhanced cuticular penetration as the mechanism for synergy of insecticidal
      constituents of rosemary essential oil in Trichoplusia ni.
AB  - Synergistic interactions between constituents of essential oils have been
      reported for several areas of research. In the present study, mechanisms that
      could explain the synergistic action of the two major insecticidal constituents
      of rosemary oil, 1,8-cineole and camphor against the cabbage looper, Trichoplusia
      ni were investigated. 1,8-Cineole was more toxic than camphor when applied
      topically to larvae, and when coadministered in their ratio naturally occurring
      in rosemary oil, the binary mixture was synergistic. However, when injected
      directly into larvae, camphor was more toxic than 1,8-cineole. GC-MS analyses
      showed that penetration of topically-applied camphor was significantly enhanced
      when it was mixed with 1,8-cineole in the natural ratio. A bioassay combining
      injection and topical application methods confirmed the increased penetration of
      both compounds when mixed, showing the same bioactivity as seen for higher
      amounts applied individually. Lowered surface tension as well as increased
      solubility of camphor by 1,8-cineole, along with the interaction between 1,8
      cineole and the lipid layer of the insect's cuticle may explain the enhanced
      penetration of camphor. Because of the similarities in biological function of
      animal and microbial membranes, our finding has potential for application in
      other fields of study. 

PMID- 26223770
TI  - Strand displacement and duplex invasion into double-stranded DNA by pyrrolidinyl
      peptide nucleic acids.
AB  - The so-called acpcPNA system bears a peptide backbone consisting of 4'
      substituted proline units with (2'R,4'R) configuration in an alternating
      combination with (2S)-amino-cyclopentane-(1S)-carboxylic acids. acpcPNA forms
      exceptionally stable hybrids with complementary DNA. We demonstrate herein (i)
      strand displacements by single-stranded DNA from acpcPNA-DNA hybrids, and by
      acpcPNA strands from DNA duplexes, and (ii) strand invasions by acpcPNA into
      double-stranded DNA. These processes were studied in vitro using synthetic
      oligonucleotides and by means of our concept of wavelength-shifting fluorescent
      nucleic acid probes, including fluorescence lifetime measurements that allow
      quantifying energy transfer efficiencies. The strand displacements of preannealed
      14mer acpcPNA-7mer DNA hybrids consecutively by 10mer and 14mer DNA strands occur
      with rather slow kinetics but yield high fluorescence color ratios (blue : yellow
      or blue : red), fluorescence intensity enhancements, and energy transfer
      efficiencies. Furthermore, 14mer acpcPNA strands are able to invade into 30mer
      double-stranded DNA, remarkably with quantitative efficiency in all studied
      cases. These processes can also be quantified by means of fluorescence. This
      remarkable behavior corroborates the extraordinary versatile properties of
      acpcPNA. In contrast to conventional PNA systems which require 3 or more
      equivalents PNA, only 1.5 equivalents acpcPNA are sufficient to get efficient
      double duplex invasion. Invasions also take place even in the presence of 250 mM
      NaCl which represents an ionic strength nearly twice as high as the physiological
      ion concentration. These remarkable results corroborate the extraordinary
      properties of acpcPNA, and thus acpcPNA represents an eligible tool for
      biological analytics and antigene applications. 

PMID- 26223771
TI  - Estimates of community exposure and health risk to sulfur dioxide from power
      plant emissions using short-term mobile and stationary ambient air monitoring.
AB  - To estimate plausible health effects associated with peak sulfur dioxide (SO2)
      levels from three coal-fired power plants in the Baltimore, Maryland, area, air
      monitoring was conducted between June and September 2013. Historically, the
      summer months are periods when emissions are highest. Monitoring included a 5-day
      mobile and a subsequent 61-day stationary monitoring study. In the stationary
      monitoring study, equipment was set up at four sites where models predicted and
      mobile monitoring data measured the highest average concentrations of SO2.
      Continuous monitors recorded ambient concentrations each minute. The 1-min data
      were used to calculate 5-min and 1-hr moving averages for comparison with
      concentrations from clinical studies that elicited lung function decrement and
      respiratory symptoms among asthmatics. Maximum daily 5-min moving average
      concentrations from the mobile monitoring study ranged from 70 to 84 ppb (183-220
      ug/m3), and maximum daily 1-hr moving average concentrations from the mobile
      monitoring study ranged from 15 to 24 ppb (39-63 ug/m3). Maximum 5-min moving
      average concentrations from stationary monitoring ranged from 39 to 229 ppb (102
      600 ug/m3), and maximum daily 1-hr average concentrations ranged from 15 to 134
      ppb (40-351 ug/m3). Estimated exposure concentrations measured in the vicinity of
      monitors were below the lowest levels that have demonstrated respiratory symptoms
      in human clinical studies for healthy exercising asthmatics. Based on 5-min and 1
      hr monitoring, the exposure levels of SO2 in the vicinity of the C.P. Crane,
      Brandon Shores, and H.A. Wagner power plants were not likely to elicit
      respiratory symptoms in healthy asthmatics. IMPLICATIONS: Mobile and stationary
      air monitoring for SO2 were conducted to quantify short-term exposure risk, to
      the surrounding community, from peak emissions of three coal-fired power plants
      in the Baltimore area. Concentrations were typically low, with only a few 5-min
      averages higher than levels indicated during clinical trials to induce changes in
      lung capacity for healthy asthmatics engaged in exercise outdoors.

PMID- 26223772
TI  - Transabdominal and transrectal ultrasonography of fetuses in Wurttemberg ewes:
      Correlation with gestational age.
AB  - It is useful to determine the gestational age in sheep to provide essential
      information for effective flock management practices. The aims of this study were
      to evaluate the efficacy and practical aspects for using two ultrasound
      techniques, transabdominal and transrectal, in determining the gestational age in
      Wurttemberg ewes. Monitoring of embryo and fetus developmental stages during the
      ewes' gestation was carried out with real time ultrasound using a transabdominal
      convex probe, frequency 3.5 MHz, and a transrectal linear probe, frequency 7.5
      MHz. The size of the embryonic vesicle during the period from the 23rd to the
      38th day of gestation can be used as a confirmational indicator of gestational
      age when the transrectal probe is used. The occipital nasal diameter correlated
      with the gestational age with both transabdominal (P < 0.05) and transrectal
      probes (P < 0.01) from the 46th to the 63rd day of gestation. The biparietal
      diameter of the fetal head measured by transabdominal probe during the period
      from the 46th to the 63rd day of gestation correlates with gestation age (P <
      0.05). The diameter of the fetal eye orbit monitored by transrectal probe from
      the 46th to the 63rd day of gestation also correlated well with gestational age
      (P < 0.05). 

PMID- 26223773
TI  - Respiratory and Metabolic Impacts of Crustacean Immunity: Are there Implications
      for the Insects?
AB  - Extensive similarities in the molecular architecture of the crustacean immune
      system to that of insects give credence to the current view that the Hexapoda,
      including Insecta, arose within the clade Pancrustacea. The crustacean immune
      system is mediated largely by hemocytes, relying on suites of pattern recognition
      receptors, effector functions, and signaling pathways that parallel those of
      insects. In crustaceans, as in insects, the cardiovascular system facilitates
      movement of hemocytes and delivery of soluble immune factors, thereby supporting
      immune surveillance and defense along with other physiological functions such as
      transport of nutrients, wastes, and hormones. Crustaceans also rely heavily on
      their cardiovascular systems to mediate gas exchange; insects are less reliant on
      internal circulation for this function. Among the largest crustaceans, the
      decapods have developed a condensed heart and a highly arteriolized
      cardiovascular system that supports the metabolic demands of their often large
      body size. However, recent studies indicate that mounting an immune response can
      impair gas exchange and metabolism in their highly developed vascular system.
      When circulating hemocytes detect the presence of potential pathogens, they
      aggregate rapidly with each other and with the pathogen. These growing aggregates
      can become trapped in the microvasculature of the gill where they are melanized
      and may be eliminated at the next molt. Prior to molting, trapped aggregates of
      hemocytes also can impair hemolymph flow and oxygenation at the gill. Small
      shifts to anaerobic metabolism only partially compensate for this decrease in
      oxygen uptake. The resulting metabolic depression is likely to impact other
      energy-expensive cellular processes and whole-animal performance. For crustaceans
      that often live in microbially-rich, but oxygen-poor aquatic environments, there
      appear to be distinct tradeoffs, based on the gill's multiple roles in
      respiration and immunity. Insects have developed a separate tracheal system for
      the delivery of oxygen to tissues, so this particular tradeoff between oxygen
      transport and immune function is avoided. Few studies in crustaceans or insects
      have tested whether mounting an immune response might impact other functions of
      the cardiovascular system or alter integrity of the gut, respiratory, and
      reproductive epithelia where processes of the attack on pathogens, defense by the
      host, and physiological functions play out. Such tradeoffs might be fruitfully
      addressed by capitalizing on the ease of molecular and genetic manipulation in
      insects. Given the extensive similarities between the insect and the crustacean
      immune systems, such models of epithelial infection could benefit our
      understanding of the physiological consequences of immune defense in all of the
      Pancrustacea. 

PMID- 26223775
TI  - Norwegian public health investigation shows that antibiotic resistance concerns
      us all.

PMID- 26223774
TI  - Caesarean section at full cervical dilatation.
AB  - BACKGROUND: Caesarean section at full cervical dilatation has many implications
      for maternal and neonatal morbidity as well as subsequent pregnancy outcomes.
      However, increasing trends are reported internationally for second-stage
      caesarean delivery. OBJECTIVES: To review the rate and indication for a caesarean
      section at full dilatation over a 5-year period at a tertiary referral obstetric
      centre in Sydney. MATERIALS AND METHODS: Retrospective cohort review of all women
      with a singleton, cephalic presenting fetus at >=37(0)  weeks' gestation
      delivered by caesarean section in the second stage of labour between 1 January
      2009 and 31 December 2013 at Royal Prince Alfred Hospital. Medical records were
      reviewed, and demographic, maternal and fetal outcome data were obtained.
      Consultant supervision and documentation standards were recorded. The main
      outcome measures were the rate of caesarean section at full cervical dilatation,
      maternal and fetal morbidity. RESULTS: During the study period, 8449/26063
      (32.4%) babies were born by caesarean section. Of these surgical births, 476
      (5.6%) were performed at full cervical dilatation at >37 weeks' gestation. There
      was no observed trend over the 5 years. The majority of women delivered by
      caesarean section at full dilatation were nulliparous and in spontaneous labour.
      More than half of these women were delivered without a trial of instrumental
      delivery. Consultant obstetricians were present for 7% of public second-stage
      caesarean deliveries. CONCLUSION: We report a 5-year experience with caesarean
      delivery at full dilatation at a tertiary unit. The rate was variable over the 5
      years. Secondary outcome measures suggest that consultant supervision is uncommon
      and documentation standards require improvement.

PMID- 26223776
TI  - Radiation dose during CT-guided percutaneous cryoablation of renal tumors: Effect
      of a dose reduction protocol.
AB  - PURPOSE: To estimate and compare the radiation dose using a standard protocol and
      that of a dose reduction protocol in patients undergoing CT-guided percutaneous
      cryoablation of renal tumors. MATERIALS AND METHODS: An IRB-approved, HIPAA
      compliant retrospective study of 97 CT-guided cryoablation procedures to treat a
      solitary renal tumor in each of 97 patients (64 M, 33 F; range 31-84 yrs) was
      performed. Fifty patients were treated using a standard dose protocol (kVp=120,
      mean mAs=180, monitoring scans every 3 min during freezes), and an additional 47
      patients were treated using a dose reduction protocol (kVp=100, mean mAs=100,
      monitoring scans less frequently than every 3 min during freezes). Multiple
      Wilcoxon Mann-Whitney (rank-sum) tests were used to compare dose-length product
      (DLP) between the two groups. Fisher's exact test was used to compare technique
      effectiveness at 12 months post ablation between the two groups. RESULTS: Median
      DLP for the standard protocol group was 4833.5 mGy*cm (range, 1667-8267 mGy*cm);
      median DLP for the dose reduction group was 2648 mGy*cm (range, 850-7169 mGy*cm),
      significantly less than that of the standard protocol group (p<0.01). The
      technique effectiveness for the dose reduction group was not significantly
      different from that of the standard protocol group at 12 month follow up
      (p=0.434). CONCLUSION: The radiation dose during percutaneous CT-guided
      cryoablation of renal tumors was substantial in both the standard and the dose
      reduction groups; however, it was significantly lower with the protocol change
      that reduced dose parameters and decreased the number of CT scans.

PMID- 26223777
TI  - Fever after lung radiofrequency ablation: Prospective evaluation of its incidence
      and associated factors.
AB  - PURPOSE: To prospectively investigate the incidence of post-lung radiofrequency
      (RF) ablation fever as well as its associated factors, according to the grade of
      fever. MATERIALS AND METHODS: A total of 56 patients who underwent 67 lung RF
      sessions were analyzed. Post-ablation fever (>= 37.0 degrees C) was graded
      according to the common toxicity criteria of adverse events v. 4.0. Fever >= 37.0
      degrees C and <38.0 degrees C was defined as grade 0 fever. The 67 RF sessions
      were divided into two groups according to the presence of post-ablation fever,
      and the factors associated with fever were determined using univariate and
      multivariate analyses. Subsequently, the RF sessions accompanied by post-ablation
      fever were further divided into two groups according to the grade of fever (grade
      0 vs. grade >= 1), and the factors associated with the grade of fever were
      determined. RESULTS: Grade 0, 1, and 2 fever accompanied 36 (54%), 11 (16%), and
      2 (3%) sessions, respectively. Post-ablation fever was significantly associated
      with larger ablated parenchymal volume (P=0.001) and development of pulmonary
      infiltration (P=0.004). Additionally, development of pulmonary infiltration
      (P=0.048) was also significantly and independently associated with higher grade
      of fever in the multivariate analysis. CONCLUSIONS: The incidences of grade 0, 1,
      and 2 post-ablation fever were 54%, 16%, and 3%, respectively. Larger ablated
      parenchymal volume and development of pulmonary infiltration were found to be
      associated with the development of post-ablation fever, with the latter being an
      independent factor associated with higher grade of fever.

PMID- 26223778
TI  - High-performance n-type black phosphorus transistors with type control via
      thickness and contact-metal engineering.
AB  - Recent work has demonstrated excellent p-type field-effect switching in
      exfoliated black phosphorus, but type control has remained elusive. Here, we
      report unipolar n-type black phosphorus transistors with switching polarity
      control via contact-metal engineering and flake thickness, combined with oxygen
      and moisture-free fabrication. With aluminium contacts to black phosphorus, a
      unipolar to ambipolar transition occurs as flake thickness increases from 3 to 13
      nm. The 13-nm aluminium-contacted flake displays graphene-like symmetric hole and
      electron mobilities up to 950 cm(2) V(-1) s(-1) at 300 K, while a 3 nm flake
      displays unipolar n-type switching with on/off ratios greater than 10(5) (10(7))
      and electron mobility of 275 (630) cm(2) V(-1) s(-1) at 300 K (80 K). For
      palladium contacts, p-type behaviour dominates in thick flakes, while 2.5-7 nm
      flakes have symmetric ambipolar transport. These results demonstrate a leap in n
      type performance and exemplify the logical switching capabilities of black
      phosphorus. 

PMID- 26223779
TI  - Risk assessment of wandering behavior in mild dementia.
AB  - OBJECTIVE: This prospective longitudinal study aims to determine the risk factors
      of wandering-related adverse consequences in community-dwelling persons with mild
      dementia. These adverse consequences include negative outcomes of wandering
      (falls, fractures, and injuries) and eloping behavior. METHODS: We recruited 143
      dyads of persons with mild dementia and their caregivers from a veteran's
      hospital and memory clinic in Florida. Wandering-related adverse consequences
      were measured using the Revised Algase Wandering Scale - Community Version.
      Variables such as personality (Big Five Inventory), behavioral response to
      stress, gait, and balance (Tinetti Gait and Balance), wayfinding ability
      (Wayfinding Effectiveness Scale), and neurocognitive abilities (attention,
      cognition, memory, language/verbal skills, and executive functioning) were also
      measured. Bivariate and logistic regression analyses were performed to assess the
      predictors of these wandering-related adverse consequences. RESULTS: A total of
      49% of the study participants had falls, fractures, and injuries due to wandering
      behavior, and 43.7% demonstrated eloping behaviors. Persistent walking (OR = 2.6)
      and poor gait (OR = 0.9) were significant predictors of negative outcomes of
      wandering, while persistent walking (OR = 13.2) and passivity (OR = 2.55)
      predicted eloping behavior. However, there were no correlations between wandering
      related adverse consequences and participants' characteristics (age, gender,
      race, ethnicity, and education), health status (Charlson comorbidity index), or
      neurocognitive abilities. CONCLUSION: Our results highlight the importance of
      identifying at-risk individuals so that effective interventions can be developed
      to reduce or prevent the adverse consequences of wandering.

PMID- 26223780
TI  - Anti-fibrotic effects of phenolic compounds on pancreatic stellate cells.
AB  - BACKGROUND: Pancreatic fibrosis is a prominent histopathological characteristic
      of chronic pancreatitis and plausibly a dynamic process of transition to the
      development of pancreatic ductal adenocarcinoma. Conversely, the activation of
      pancreatic stellate cells (PSCs) has been recently suggested as the key
      initiating step in pancreatic fibrosis. As natural polyphenols had been largely
      applied in complementary therapies in the past decade, in this study, we aimed to
      investigate which groups of phenolic compounds exert promising inhibitory actions
      on fibrogenesis as there are few effective strategies for the treatment of
      pancreatic fibrosis to date. METHODS: We examined the anti-fibrotic effects of a
      variety of herbal constituents using a cellular platform, the LTC-14 cells, which
      retained essential characteristics and morphologies of primary PSCs, by means of
      various biochemical assays including cell viability test, real-time polymerase
      chain reaction and Western blotting analysis. RESULTS: Among a number of commonly
      used herbal constituents, we found that the application of rhein, emodin,
      curcumin and resveratrol significantly suppressed the mRNA and protein levels of
      several fibrotic mediators namely alpha-smooth muscle actin, type I collagen and
      fibronectin in LTC-14 cells against transforming growth factor-beta stimulation.
      Though the values of cytotoxicity varied, the mechanism of the anti-fibrotic
      action of these four phenolic compounds was principally associated with a
      decrease in the activation of the nuclear factor-kappaB signaling pathway.
      CONCLUSIONS: Our findings suggest that the mentioned phenolic compounds may serve
      as anti-fibrotic agents in PSC-relating disorders and pathologies, particularly
      pancreatic fibrosis.

PMID- 26223781
TI  - Cultural adaptation of a brief motivational intervention for heavy drinking among
      Hispanics in a medical setting.
AB  - BACKGROUND: Hispanics, particularly men of Mexican origin, are more likely to
      engage in heavy drinking and experience alcohol-related problems, but less likely
      to obtain treatment for alcohol problems than non-Hispanic men. Our previous
      research indicates that heavy-drinking Hispanics who received a brief
      motivational intervention (BMI) were significantly more likely than Hispanics
      receiving standard care to reduce subsequent alcohol use. Among Hispanics who
      drink heavily the BMI effectively reduced alcohol use but did not impact alcohol
      related problems or treatment utilization. We hypothesized that an adapted BMI
      that integrates cultural values and addresses acculturative stress among
      Hispanics would be more effective. METHODS/DESIGN: We describe here the protocol
      for the design and implementation of a randomized (approximately 300 patients per
      condition) controlled trial evaluating the comparative effectiveness of a
      culturally adapted (CA) BMI in contrast to a non-adapted BMI (NA-BMI) in a
      community hospital setting among men of Mexican origin. Study participants will
      include men who were hospitalized due to an alcohol related injury or screened
      positive for heavy drinking. By accounting for risk and protective factors of
      heavy drinking among Hispanics, we hypothesize that CA-BMI will significantly
      decrease alcohol use and alcohol problems, and increase help-seeking and
      treatment utilization. DISCUSSION: This is likely the first study to directly
      address alcohol related health disparities among non-treatment seeking men of
      Mexican origin by comparing the benefits of a CA-BMI to a NA-BMI. This study
      stands to not only inform interventions used in medical settings to reduce
      alcohol-related health disparities, but may also help reduce the public health
      burden of heavy alcohol use in the United States. TRIAL REGISTRATION: Trial
      registration clinicaltrials.gov identifier NCT02429401; Registration date: April
      28, 2015.

PMID- 26223782
TI  - Involving patients in enrolment decisions for acute myocardial infarction trials.

PMID- 26223784
TI  - Predictors of health-related quality of life in patients with irritable bowel
      syndrome. A cross-sectional study in Norway.
AB  - BACKGROUND: Reduced quality of life (QoL) is often the main problem for patients
      with irritable bowel syndrome (IBS). This study aimed at finding predictors of
      reduced physical and mental quality of life (QoL) accessible for intervention.
      METHODS: Consecutive patients with IBS (according to the Rome II criteria)
      visiting a general practitioner were included in a prospective cohort study and
      followed up for 6-9 months. At the last visit, information about sociodemographic
      characteristics, abdominal complaints, QoL and a range of physical and mental
      comorbidities were collected. Physical and mental QoL were measured with the
      generic QoL instrument Short Form-12 Physical Component Score (SF-12 PCS) and
      Short Form-12 Mental Component Score (SF-12 MCS) respectively. The normal scores
      are 50. This cross-sectional study used data from the last visit. RESULTS: Out of
      208 patients included in the cohort study, 149 (female/male: 105/44) with a mean
      age of 52 years (SD 15.3) were available for the analyses. Physical and mental
      QoL were reduced, the mean SF-12 PCS and SF-12 MCS scores were 38.4 (SD 11.9) and
      45.0 (SD 11.3) respectively. The main independent predictors of low SF-12 PCS and
      SF-12 MCS were subjective health complaints and organic diseases, and affective
      disorders respectively. The severity of IBS symptoms was of minor clinical
      importance. CONCLUSIONS: To help patients with IBS and reduced QoL, treatment
      should focus on QoL and not on relief of IBS symptoms. The different causes of
      reduced physical and mental QoL make an individually directed treatment
      necessary.

PMID- 26223785
TI  - ICD-10 and its Impact on our Practice.

PMID- 26223783
TI  - Studies of lipopolysaccharide effects on the induction of alpha-synuclein
      pathology by exogenous fibrils in transgenic mice.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder
      that is pathologically characterized by loss of dopaminergic neurons from the
      substantia nigra, the presence of aggregated alpha-synuclein (alphaS) and
      evidence of neuroinflammation. Experimental studies have shown that the cerebral
      injection of recombinant fibrillar alphaS, especially in alphaS transgenic mouse
      models, can induce the formation and spread of alphaS inclusion pathology.
      However, studies reporting this phenomenon did not consider the presence of
      lipopolysaccharide (LPS) in the injected alphaS, produced in E. coli, as a
      potential confound. The objectives of this study are to develop a method to
      remove the LPS contamination and investigate the differences in pathologies
      induced by alphaS containing LPS or alphaS highly purified of LPS. RESULTS AND
      CONCLUSIONS: We were able to remove >99.5% of the LPS contamination from the
      alphaS preparations through the addition of a cation exchange step during
      purification. The alphaS pathology induced by injection of fibrils produced from
      alphaS containing LPS or purified of LPS, showed a similar distribution pattern;
      however, there was less spread into the cortex of the mice injected with alphaS
      containing higher levels of LPS. As previously reported, injection of alphaS
      fibrils could induce astrogliosis, and alphaS inclusions were present within
      astrocytes in mice injected with fibrils comprised of alphaS with or without
      cation exchange purification. Furthermore, we identified the presence of alphaS
      pathology in ependymal cells in both groups of mice, which suggests the
      involvement of a novel mechanism for spread in this model of alphaS pathology.

PMID- 26223786
TI  - Prevalence of stress among medical students: a comparative study between public
      and private medical schools in Bangladesh.
AB  - BACKGROUND: Throughout the world all health professionals face stress because of
      time-pressures, workload, multiple roles and emotional issues. Stress does not
      only exist among the health professionals but also in medical students.
      Bangladesh has currently 77 medical colleges 54 of which are private. This study
      was designed to collect baseline data of stress-level among Bangladeshi students,
      which we believe will form the basis for further in depth studies. METHODS: A
      cross-sectional study was conducted on medical students from 2 public and 6
      private medical-schools in Bangladesh. All medical schools have common curriculum
      formulated by the Government of Bangladesh. The study population was 1,363
      medical students of Year-III and IV of academic session 2013/2014. Universal
      sampling technique was used. The period of study was February to June 2014. Data
      was collected using a validated instrument, compiled and analysed using SPSS
      version-20. RESULTS: A total of 990 (73%) out 1,363 medical students participated
      in the study, of which 36% were male and 64% were female. The overall prevalence
      of stress of the study population was 54%. 53% of male and 55% of female were
      reported suffering from stress. 54% of Year-III students and 55% of Year-IV were
      noted suffering from stress. There was statistically significant (p = 0.005)
      differences in the level of stress between public (2.84 +/- 0.59) and private
      (2.73 +/- 0.57) medical schools student. CONCLUSIONS: More than half of
      Bangladeshi medical students are suffering from measureable academic stress. It
      would be pertinent if the relevant authorities could address the issue so as to
      provide a conducive medical learning environment.

PMID- 26223788
TI  - Coordination polymers from a highly flexible alkyldiamine-derived ligand:
      structure, magnetism and gas adsorption studies.
AB  - The synthesis and structural, magnetic and gas adsorption properties of a series
      of coordination polymer materials prepared from a new, highly flexible and
      internally functional tetrakis-carboxybenzyl ligand H4L derived from 1,2
      diaminoethane have been examined. The compound poly-[Ni3(HL)2(OH2)4].2DMF.2H2O 1,
      a two-dimensional coordination polymer, contains aqua- and carboxylato-bridged
      trinuclear Ni(II) clusters, the magnetic behaviour of which can be well described
      through experimental fitting and ab initio modelling to a ferromagnetically
      coupled trimer with a positive axial zero-field splitting parameter D. Compound
      poly-[Zn2L].2DMF.3H2O 2, a three-dimensional coordination polymer displaying frl
      topology, contains large and well-defined solvent channels, which are shown to
      collapse on solvent exchange or drying. Compound poly-[Zn2(L)(DMSO)4].3DMSO.3H2O
      3, a highly solvated two-dimensional coordination polymer, displayed poor
      stability characteristics, however a structurally related material poly
      [Zn2(L)(bpe)(DMSO)2].DMSO.3H2O 4 was prepared under similar synthetic conditions
      by including the 1,2-bis(4-pyridyl)ethylene bpe co-ligand. Compound 4, containing
      small one-dimensional solvent channels, shows excellent structural resilience to
      solvent exchange and evacuation, and the evacuated material displays selective
      adsorption of CO2 over N2 at 273 K in the pressure range 0-1 atm. Each of the
      coordination polymers displays subtle differences in the conformation and binding
      mode of the ligand species, with switching between two distinct conformers (X
      shaped and H-shaped), as well as a variable protonation state of the central
      core, with significant effects on the resulting network structures and physical
      properties of the materials. 

PMID- 26223787
TI  - Assessment of self-restraint using a functional analysis of self-injury.
AB  - When self-restraint and self-injurious behavior (SIB) co-occur, self-restraint
      might be maintained by negative reinforcement through the removal of SIB. The
      current study evaluated this possibility with an individual who exhibited hand-to
      head SIB. Three functional analyses of SIB were conducted: (a) no consequences
      for self-restraint, (b) self-restraint blocked, and (c) hypothesized aversive
      effects of SIB blocked. The outcomes of the 3 analyses suggested that self
      restraint was maintained by negative reinforcement. 

PMID- 26223789
TI  - Interactions of Condensed Tannins with Saccharomyces cerevisiae Yeast Cells and
      Cell Walls: Tannin Location by Microscopy.
AB  - Interactions between grape tannins/red wine polyphenols and yeast cells/cell
      walls was previously studied within the framework of red wine aging and the use
      of yeast-derived products as an alternative to aging on lees. Results evidenced a
      quite different behavior between whole cells (biomass grown to elaborate yeast
      derived products, inactivated yeast, and yeast inactivated after autolysis) and
      yeast cell walls (obtained from mechanical disruption of the biomass). Briefly,
      whole cells exhibited a high capacity to irreversibly adsorb grape and wine
      tannins, whereas only weak interactions were observed for cell walls. This last
      point was quite unexpected considering the literature and called into question
      the real role of cell walls in yeasts' ability to fix tannins. In the present
      work, tannin location after interactions between grape and wine tannins and yeast
      cells and cell walls was studied by means of transmission electron microscopy,
      light epifluorescence, and confocal microscopy. Microscopy observations evidenced
      that if tannins interact with cell walls, and especially cell wall mannoproteins,
      they also diffuse freely through the walls of dead cells to interact with their
      plasma membrane and cytoplasmic components. 

PMID- 26223790
TI  - Effects of Yerba Mate (IIex paraguariensis) on Histomorphometry, Biomechanics,
      and Densitometry on Bones in the Rat.
AB  - Yerba mate (Ilex paraguariensis) is a xanthine-containing beverage, which is also
      rich in caffeine. Because caffeine has a negative impact on bone mineral density
      (BMD) mainly associated with low calcium (Ca) diets, there would be expected a
      negative effect of yerba mate on bone. In this study, Sprague-Dawley rats were
      used and randomly assigned into four groups (n = 6/group): Control + Ca 0.2 g %;
      Control + Ca 0.9 g %; Yerba + Ca 0.2 g %; Yerba + Ca 0.9 g %. At the end of the
      experiment, tibias and femurs were obtained for BMD, morphometric,
      histomorphometric, and biomechanical analyses. While there was no difference in
      bone parameters between rats with and without yerba mate consumption, a negative
      effect of low Ca diet was observed in BMD, morphometric, histomorphometric, and
      biomechanical results. Interaction between Ca content in the diet and yerba mate
      was only found in trabecular bone volume, which would indicate that the negative
      effect of low Ca intake on bone volume is reversed in part by yerba mate
      infusion. However, yerba mate was not able to reverse the negative effect of low
      Ca content on biomechanical properties and trabecular connectivity. In summary,
      at least in our study, yerba mate would not have a negative effect on bone and
      would be safe for the bone health of consumers. 

PMID- 26223791
TI  - Definitions of Sarcopenia: Associations with Previous Falls and Fracture in a
      Population Sample.
AB  - Sarcopenia is common in later life and may be associated with adverse health
      outcomes such as disability, falls and fracture. There is no consensus definition
      for its diagnosis although diagnostic algorithms have been proposed by the
      European Working Group for Sarcopenia in Older People (EWGSOP), the International
      Working Group on Sarcopenia (IWGS) and the Foundation for the National Institutes
      of Health Sarcopenia Project (FNIH). More recently, Binkley and colleagues
      devised a score-based system for the diagnosis of "dysmobility syndrome" in an
      attempt to combine adverse musculoskeletal phenotypes, including sarcopenia and
      osteoporosis, in order to identify older individuals at particular risk. We
      applied these criteria to participants from the Hertfordshire Cohort Study to
      define their prevalence in an unselected cohort of UK community-dwelling older
      adults and assess their relationships with previous falls and fracture. Body
      composition and areal bone mineral density were measured using dual-energy X-ray
      absorptiometry, gait speed was determined by a 3-m walk test and grip strength
      was assessed with a Jamar hand-held dynamometer. Researcher-administered
      questionnaires were completed detailing falls and fracture history. The
      prevalence of sarcopenia in this cohort was 3.3, 8.3 and 2.0% using the EWGSOP,
      IWGS and related definition of FNIH, respectively; 24.8% of individuals had
      dysmobility syndrome. Individuals with dysmobility reported significantly higher
      number of falls (last year and since the age of 45 years) (p < 0.01) than those
      without it, but no increased fracture rate was observed in this group (p = 0.96).
      Those with sarcopenia as defined by the IWGS reported significantly higher falls
      in the last year and prevalent fractures (falls in the last year: OR 2.51; CI
      1.09-5.81; p = 0.03; fractures OR 2.50; CI 1.05-5.92; p = 0.04) but these
      significant associations were not seen when the EWGSOP definition was applied.
      The IWGS definition of sarcopenia appears to be an effective means of identifying
      individuals at risk of prevalent adverse musculoskeletal events.

PMID- 26223792
TI  - Synthesis and characterization of polystyrene embolization particles doped with
      tantalum oxide nanoparticles for X-ray contrast.
AB  - Radiopaque and fluorescent embolic particles have been synthesized and
      characterised to match the size of vasculature found in tumours to ensure
      effective occlusion of the vessels. A literature search showed that the majority
      of vessels surrounding a tumour were less than 50 um and therefore polydispersed
      polystyrene particles with a peak size of 50 um have been synthesised. The
      embolic particles contain 5-8 nm amorphous tantalum oxide nanoparticles which
      provide X-ray contrast. Embolic particles containing up to 9.4 wt% tantalum oxide
      were prepared and showed significant contrast compared to the undoped polystyrene
      particles. The X-ray contrast of the embolic particles was shown to be linear
      (R(2) = 0.9) with respect to the concentration of incorporated tantalum
      nanoparticles. A model was developed which showed that seventy-five 50 um embolic
      particles containing 10% tantalum oxide could provide the same contrast as 5 cm
      of bone. Therefore, the synthesized particles would provide sufficient X-ray
      contrast to enable visualisation within a tumour.

PMID- 26223793
TI  - Dermatophytosis in farmed mink (Mustela vison) caused by Trichophyton equinum.
AB  - This report details 2 outbreaks of dermatophytosis in 2 different mink ranches.
      On the first farm, only kits were affected, while on the second farm, small
      numbers of adults were infected. Affected mink were otherwise clinically healthy
      and in good body condition. Three animals were euthanized and submitted for
      autopsy. Grossly, mink exhibited locally extensive to coalescing areas of
      crusting alopecia but no other significant gross lesions in internal organs.
      Microscopically, skin lesions were characterized by chronic hyperplastic
      dermatitis with folliculitis, furunculosis, occasional intracorneal pustules, and
      large numbers of intrafollicular fungal arthrospores and hyphae. The dermatophyte
      was cultured and identified as Trichophyton equinum based on molecular barcoding
      of the internal transcribed spacer region of the ribosomal DNA gene. 

PMID- 26223794
TI  - Semiconducting Polymer Nanoparticles with Persistent Near-Infrared Luminescence
      for In Vivo Optical Imaging.
AB  - Materials with persistent luminescence are attractive for in vivo optical imaging
      since they have a long lifetime that allows the separation of excitation of
      fluorophores and image acquisition for time-delay imaging, thus eliminating
      tissue autofluorescence associated with fluorescence imaging. Persistently
      luminescent nanoparticles have previously been fabricated from toxic rare-earth
      metals. This work reports that nanoparticles made of the conjugated polymer MEH
      PPV can generate luminescence persisting for an hour upon single excitation. A
      near-infrared dye was encapsulated in the conjugated polymer nanoparticle to
      successfully generate persistent near-infrared luminescence through resonance
      energy transfer. This new persistent luminescence nanoparticles have been
      demonstrated for optical imaging applications in living mice. 

PMID- 26223795
TI  - Hepatitis B virus sero-profiles and genotypes in HIV-1 infected and uninfected
      injection and Non-injection drug users from coastal Kenya.
AB  - BACKGROUND: Information about HBV sero-markers, infection stages and genotypes in
      HIV-1 infected and uninfected injection and non-injection drug users (IDUs) in
      Kenya remains elusive. METHODS: A cross-sectional study examining HBV sero
      marker, infection stages and genotypes was conducted among HIV-1 infected and
      uninfected, respectively, IDUs (n = 157 and n = 214) and non-IDUs (n = 139 and n
      = 48), and HIV-1 uninfected non-drug using controls (n = 194) from coastal,
      Kenya. HBV sero-marker and infection stages were based on HBV 5-panel rapid test
      plasma sero-reactivity. DNA was extracted from acute and chronic plasma samples
      and genotypes established by nested-PCR and direct sequencing. RESULTS: HBsAg
      positivity was higher in HIV-1 infected IDUs (9.6%) relative to HIV-1 uninfected
      IDUs (2.3%), HIV-1 infected non-IDUs (3.6%), HIV-1 uninfected non-IDUs (0.0%) and
      non-drug users (2.6%; P = 0.002). Contrastingly, HBsAb positivity was higher in
      HIV-1 uninfected IDUs (14.6%) and non-IDUs (16.8) in comparison to HIV-1 infected
      IDUs (8.3%), and non-IDUs (8.6%), and non-drug users (8.2%; P = 0.023). HBcAb
      positivity was higher in HIV-1 infected IDUs (10.2%) compared to HIV-1 uninfected
      IDUs (3.3%), HIV-1 infected non-IDUs (6.5%), HIV-1 uninfected non-IDUs (2.1%) and
      non-drug users (4.6%; P = 0.038). Acute (5.7%, 1.4%, 0.0%, 0.0% and 1.5%) and
      chronic (5.1%, 0.9%, 3.6%, 0.0% and 1.5%) stages were higher in HIV-1 infected
      IDUs, compared to HIV-1 uninfected IDUs, HIV-1 infected and uninfected non-IDUs
      and non-drug users, respectively. However, vaccine type response stage was higher
      in HIV-1 uninfected IDUs (15.4%) relative to HIV-1 infected IDUs (6.4%), and HIV
      1 infected (6.5%), and uninfected (10.4%) non-IDUs, and non-drug users (5.7%; P =
      0.003). Higher resolved infection rates were also recorded in HIV-1 uninfected
      IDUs (11.2%) compared to HIV-1 infected IDUs (8.3%), and HIV-1 infected (7.2%),
      uninfected (6.3%) non-IDUs, and non-drug users (6.7%; P = 0.479), respectively.
      Only A1 genotype showing minimal diversity was detected among the study
      participants. CONCLUSION: HBV sero-markers and infection staging are valuable in
      diagnosis and genotyping of HBV infections. Among IDUs, higher HBsAg and HBcAb
      positivity in HIV-1 infected and higher HBsAb positivity in HIV-1 negative IDUs
      suggests frequent exposure. Additionally, HBV genotype A is the dominant
      circulating genotype in both high and low risk populations of Kenya.

PMID- 26223796
TI  - Role of SIRT3 in Angiotensin II-induced human umbilical vein endothelial cells
      dysfunction.
AB  - BACKGROUND: SIRT3, a member of the sirtuin family of NAD(+)-dependent
      deacetylases, resides primarily in the mitochondria and has been shown to
      deacetylate several metabolic and respiratory enzymes that regulate important
      mitochondrial functions. Previous researches show an important role of SIRT3 in
      regulating the production of reactive oxygen species (ROS), and highlight the
      ability of SIRT3 to protect cells from oxidative damage. A key substance of renin
      angiotensin-aldosterone system (RAAS), Angiotensin II (AngII) can induce cells
      dysfunction by increasing the production of ROS. In this paper, we focus on the
      role of SIRT3 in AngII-induced human umbilical vein endothelial cells (HUVECs)
      dysfunction. METHODS: To study the influence of AngII on SIRT3 expression, HUVECs
      were treated with AngII of 10(-7), 10(-6), 10(-5) mol/L for 24 h. SIRT3
      expression was detected by wester-blotting analysis and RT-PCR. In addition, to
      research the role of SIRT3 in AngII-induced HUVECs,we used SIRT3 siRNA to knock
      down SIRT3 expression in HUVECs. Cells pretreated with negative control siRNA or
      SIRT3 siRNA were exposed to AngII for 24 h, and endothelial nitric oxide synthase
      (eNOS) expression, eNOS activity, total level of nitric oxide (NO) and ROS
      generation of each group were detected. RESULTS: Here we show that AngII
      treatment could increase generation of ROS, and decrease eNOS activity and total
      level of NO, while upregulated eNOS expression as a compensatory mechanism. The
      stimulation of AngII upregulated the expression of SIRT3 in HUVECs. SIRT3 siRNA
      worsen the AngII-induced effects above, besides, downregulated eNOS protein
      expression. CONCLUSION: These data suggest that SIRT3 plays a role of protection
      in AngII-induced HUVECs dysfunction via regulation of ROS generation.

PMID- 26223797
TI  - Methemoglobinemia secondary to rasburicase in cancer: Non drug-related oxidative
      stress.

PMID- 26223798
TI  - Comparison between a new electronic bidet and conventional sitz baths: a
      manometric evaluation of the anal resting pressure in normal healthy volunteers.
AB  - BACKGROUND: A bidet has been proposed as a replacement for the sitz bath. Like a
      sitz bath, it brings water into contact with the perineum. However, the high
      force of water from commercially used electronic bidets may harm the anus. We
      developed a new electronic bidet and evaluated its effects on anal resting
      pressure compared with a warm sitz bath. METHODS: Forty volunteers used the
      electronic bidet and sitz bath on separate days. The electronic bidet was newly
      designed with warm (38  degrees C) water and very low force (10 mN) with a
      fountain type of flow. Anal resting pressure at the high-pressure zone was
      measured before (control) and after the electronic bidet and sitz bath. Pressure
      changes after bidet or sitz bath were expressed as percentages compared with
      control. Water temperatures and rectal temperatures were also recorded. RESULTS:
      The anal resting pressures before the electronic bidet and sitz bath were 90.2 +/
      24.6 and 88.1 +/- 16.8 mmHg, respectively. At 3 min after the electronic bidet
      and sitz bath, the anal resting pressures were 71.3 +/- 23.4 and 69.6 +/- 19.8
      mmHg, respectively. The pressure changes compared with the control were 78.2 +/-
      12.9 and 78.1 +/- 12.5%, respectively, which were not significantly different.
      The maximal increase and minimal decrease were not significantly different. The
      rectal temperature was not elevated, and the water temperature decreased
      significantly with the sitz bath (p < 0.001). CONCLUSIONS: Our new electronic
      bidet may reduce the anal resting pressure much like a warm sitz bath does.

PMID- 26223799
TI  - BDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation
      Through the Proteasome.
AB  - Brain-derived neurotrophic factor (BDNF) promotes synaptic strengthening through
      the regulation of kinase and phosphatase activity. Conversely, striatal-enriched
      protein tyrosine phosphatase (STEP) opposes synaptic strengthening through
      inactivation or internalization of signaling molecules. Here, we investigated
      whether BDNF regulates STEP levels/activity. BDNF induced a reduction of STEP61
      levels in primary cortical neurons, an effect that was prevented by inhibition of
      tyrosine kinases, phospholipase C gamma, or the ubiquitin-proteasome system
      (UPS). The levels of pGluN2B(Tyr1472) and pERK1/2(Thr202/Tyr204), two STEP
      substrates, increased in BDNF-treated cultures, and blockade of the UPS prevented
      STEP61 degradation and reduced BDNF-induced GluN2B and ERK1/2 phosphorylation.
      Moreover, brief or sustained cell depolarization reduced STEP61 levels in
      cortical neurons by different mechanisms. BDNF also promoted UPS-mediated STEP61
      degradation in cultured striatal and hippocampal neurons. In contrast, nerve
      growth factor and neurotrophin-3 had no effect on STEP61 levels. Our results thus
      indicate that STEP61 degradation is an important event in BDNF-mediated effects.

PMID- 26223800
TI  - Can Exercise Ameliorate Aromatase Inhibitor-Induced Cognitive Decline in Breast
      Cancer Patients?
AB  - Aromatase inhibitors (AIs) have been commonly used as an effective adjuvant
      therapy in treatment of breast cancer, especially for menopausal women with
      estrogen receptor-positive breast cancer. Due to the nature of aromatase, the key
      enzyme for endogenous estrogen synthesis, inhibitory of aromatase-induced side
      effects, such as cognitive impairment has been reported in both human and animal
      studies. While extensive evidence suggested that physical exercises can improve
      learning and memory activity and even prevent age-related cognitive decline,
      basic research revealed some common pathways between exercise and estrogen
      signaling that affected cognitive function. This review draws on clinical and
      basic studies to assess the potential impact of exercise in cognitive function
      from women treated with AIs for breast cancer and explore the potential mechanism
      and effects of exercise on estrogen-related cognition.

PMID- 26223801
TI  - Extremely Low Frequency Magnetic Field (ELF-MF) Exposure Sensitizes SH-SY5Y Cells
      to the Pro-Parkinson's Disease Toxin MPP(.).
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      dopaminergic neuron loss, with an etiopathogenesis involving both genetic and
      environmental factors. The occupational/residential exposure to the
      electromagnetic fields has been recently associated with an increased risk of
      neurodegenerative diseases; it has been thus proposed that the extremely low
      frequency magnetic field (ELF-MF) may contribute to neurodegenerative
      etiopathogenesis, as its interaction with biological systems directly impairs
      redox homeostasis in specific areas of the brain. The molecular mechanisms
      elicited by ELF-MF, and their potential involvement in PD onset, still remain
      unclear. To this end, we set up a generator of ELF-MF able to stably and
      homogeneously reproduce environmental prolonged exposure to ELF-MF (50 Hz, 1 mT).
      Results obtained indicate that ELF-MF exposure alters cell response of SH-SY5Y
      cells to MPP(+). We demonstrate that ELF-MF does not affect per se survival,
      shape, and morphology of both proliferating and differentiated SH-SY5Y cells but
      significantly impairs redox homeostasis and thiol content, triggering an increase
      in protein carbonylation. As a result, toxicity of MPP(+), even at low doses, is
      highly enhanced in ELF-MF-exposed cells due to a significant increase in ROS
      levels, potentiation of oxidative damage, and induction of a caspase-dependent
      apoptosis. Pre-incubation with the thiol antioxidants N-acetyl-L-cysteine and GSH
      ethyl-ester significantly reduces the extent of oxidative damage and protects
      cells from death induced by the combined treatment ELF-MF/MPP(+). Taken overall,
      our results demonstrate the redox-based molecular interaction between ELF-MF and
      PD neurotoxins in vitro, and open a new scenario for defining the synergy of
      environmental factors in PD onset.

PMID- 26223802
TI  - ALCAR Exerts Neuroprotective and Pro-Neurogenic Effects by Inhibition of Glial
      Activation and Oxidative Stress via Activation of the Wnt/beta-Catenin Signaling
      in Parkinsonian Rats.
AB  - Oxidative stress and neuroinflammation are known causative factors in progressive
      degeneration of dopaminergic (DAergic) neurons in Parkinson's disease (PD).
      Neural stem cells (NSCs) contribute in maintaining brain plasticity; therefore,
      survival of NSCs and neuroblasts during neurodegenerative process becomes
      important in replenishing the pool of mature neuronal population. Acetyl-L
      carnitine (ALCAR), present in almost all body cells, increases endogenous
      antioxidants and regulates bioenergetics. Currently, no information is available
      about the putative mechanism and neuroprotective effects of ALCAR in 6
      hydroxydopamine (6-OHDA)-induced rat model of PD-like phenotypes. Herein, we
      investigated the effect of ALCAR on death/survival of DAergic neurons,
      neuroblasts and NSCs and associates mechanism of neuroprotection in 6-OHDA
      induced rat model of PD-like phenotypes. ALCAR (100 mg/kg/day, intraperitoneal
      (i.p.)) treatment started 3 days prior to 6-OHDA lesioning and continued for
      another 14 day post-lesioning. We found that ALCAR pretreatment in 6-OHDA
      lesioned rats increased expression of neurogenic and the Wnt pathway genes in the
      striatum and substantia nigra pars compacta (SNpc) region. It suppressed the
      glial cell activation, improved antioxidant status, increased NSC/neuroblast
      population and rescued the DAergic neurons in nigrostriatal pathway. ALCAR
      pretreatment in 6-OHDA-lesioned rats decreased GSK-3beta activation and increased
      nuclear translocation of beta-catenin. Functional deficits were restored
      following ALCAR pretreatment in 6-OHDA-lesioned rats as demonstrated by improved
      motor coordination and rotational behaviour, confirming protection of DAergic
      innervations in lesioned striatum. These results indicate that ALCAR exerts
      neuroprotective effects through the activation of Wnt/beta-catenin pathway,
      suggesting its therapeutic use to treat neurodegenerative diseases by enhancing
      regenerative capacity.

PMID- 26223805
TI  - Elevated body temperature is linked to fatigue in an Italian sample of relapsing
      remitting multiple sclerosis patients.
AB  - Elevated body temperature was recently reported for the first time in patients
      with relapsing-remitting multiple sclerosis (RRMS) relative to healthy controls.
      In addition, warmer body temperature was associated with worse fatigue. These
      findings are highly novel, may indicate a novel pathophysiology for MS fatigue,
      and therefore warrant replication in a geographically separate sample. Here, we
      investigated body temperature and its association to fatigue in an Italian sample
      of 44 RRMS patients and 44 age- and sex-matched healthy controls. Consistent with
      our original report, we found elevated body temperature in the RRMS sample
      compared to healthy controls. Warmer body temperature was associated with worse
      fatigue, thereby supporting the notion of endogenous temperature elevations in
      patients with RRMS as a novel pathophysiological factor underlying fatigue. Our
      findings highlight a paradigm shift in our understanding of the effect of heat in
      RRMS, from exogenous (i.e., Uhthoff's phenomenon) to endogenous. Although
      randomized controlled trials of cooling treatments (i.e., aspirin, cooling
      garments) to reduce fatigue in RRMS have been successful, consideration of
      endogenously elevated body temperature as the underlying target will enhance our
      development of novel treatments. 

PMID- 26223803
TI  - Organotypic Hippocampal Slices as Models for Stroke and Traumatic Brain Injury.
AB  - Organotypic hippocampal slice cultures (OHSCs) have been used as a powerful ex
      vivo model for decades. They have been used successfully in studies of neuronal
      death, microglial activation, mossy fiber regeneration, neurogenesis, and drug
      screening. As a pre-animal experimental phase for physiologic and pathologic
      brain research, OHSCs offer outcomes that are relatively closer to those of whole
      animal studies than outcomes obtained from cell culture in vitro. At the same
      time, mechanisms can be studied more precisely in OHSCs than they can be in vivo.
      Here, we summarize stroke and traumatic brain injury research that has been
      carried out in OHSCs and review classic experimental applications of OHSCs and
      its limitations.

PMID- 26223804
TI  - Molecular regulation of hypothalamic development and physiological functions.
AB  - The hypothalamus is composed of many heterogeneous nuclei that control distinct
      physiological functions. Investigating molecular mechanisms that regulate the
      specification of these nuclei and specific neuronal subtypes, and their
      contribution to diverse hypothalamic functions, is an exciting research focus.
      Here, we begin by summarizing the hypothalamic functions of feeding regulation,
      sleep-wake cycles, stress responses, and circadian rhythm, and describing their
      anatomical bases. Next, we review the molecular regulation of formation of
      hypothalamic territories, specification of nuclei and subnuclei, and generation
      of specific neurons. Finally, we highlight physiological and behavioral
      consequences of altered hypothalamic development. Identifying molecules that
      regulate hypothalamic development and function will increase our understanding of
      hypothalamus-related disorders, such as obesity and diabetes, and aid in the
      development of therapies aimed specifically at their etiologies.

PMID- 26223806
TI  - The full spectrum of ethical issues in the care of patients with ALS: a
      systematic qualitative review.
AB  - Dealing systematically with ethical issues in amyotrophic lateral sclerosis (ALS)
      care requires an unbiased awareness of all the relevant ethical issues. The aim
      of the study was to determine systematically and transparently the full spectrum
      of ethical issues in ALS care. We conducted a systematic review in Medline and
      Google Books (restricted to English and German literature published between 1993
      and 2014). We applied qualitative text analysis and normative analysis to
      categorise the spectrum of ethical issues in ALS care. The literature review
      retrieved 56 references that together mentioned a spectrum of 103 ethical issues
      in ALS care. The spectrum was structured into six major categories that consist
      of first and second-order categories of ethical issues. The systematically
      derived spectrum of ethical issues in ALS care presented in this paper raises
      awareness and understanding of the complexity of ethical issues in ALS care. It
      also offers a basis for the systematic development of informational and training
      materials for health professionals, patients and their relatives, and society as
      a whole. Finally, it supports a rational and fair selection of all those ethical
      issues that should be addressed in health policies, position papers and clinical
      practice guidelines. Further research is needed to identify ways to
      systematically select the most relevant ethical issues not only in the clinical
      environment, but also for the development of clinical practice guidelines. 

PMID- 26223807
TI  - DNA methylation plasticity contributes to the natural history of metastasis.

PMID- 26223808
TI  - Survival benefit associated with early cyclosporine treatment for dermatomyositis
      associated interstitial lung disease.
AB  - Interstitial lung disease (ILD) is the most common cause of death in
      dermatomyositis (DM). Cyclosporine A (CsA) has shown to be effective in DM
      associated ILD (DM-ILD). This study aimed to define the optimal time of CsA
      administration. A total of 47 patients with DM-ILD, who were treated with CsA at
      Seoul National University Hospital between January 1998 and June 2013, were
      enrolled. ILD was diagnosed based on typical chest high-resolution computed
      tomography (HRCT) findings. Patients with early and delayed CsA treatment were
      compared in regard to the mortality and ILD progression on HRCT. The early (n =
      16) and the delayed treatment group (n = 31) did not differ in regard to baseline
      clinical characteristics including HRCT scores and pulmonary function. Patients
      with clinically amyopathic DM (CADM) were more common in the early treatment
      group. The mortality rate was significantly lower in the early treatment group
      than in the delayed treatment group (p = 0.009). The survival benefit of early
      CsA treatment remained significant even after adjusting for age, degree of
      dyspnea, CADM status, and the year of CsA treatment (hazard ratio 0.057, 95 %
      confidence interval 0.007-0.472). CsA stabilized disease progression on HRCT in
      the early treatment group (p = 0.738). Delay in CsA treatment is associated with
      a worse survival in patients with DM-ILD. Early CsA treatment should be
      considered at DM-ILD diagnosis especially in patients at a higher risk of
      developing a rapidly progressive ILD.

PMID- 26223809
TI  - The utility of pregnancy-associated plasma protein A for determination of
      prognosis in a cohort of patients with coronary artery disease.
AB  - BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is discussed as a
      biomarker representing unstable plaques in coronary artery disease (CAD).
      METHODS: In this study 927 patients with CAD (534 with stable angina and 393 with
      acute coronary syndrome [ACS]) and 217 patients without CAD and measured PAPP-A
      levels were included. Follow-up for a median of 5 years was documented. RESULTS:
      Rising quartiles of PAPP-A concentration had a higher cardiovascular mortality in
      the overall cohort of patients with CAD (p = 0.002) and the cohort with ACS (p =
      0.01). Patients with suspected ACS below the LOD for troponin I but elevated PAPP
      A levels had an increased cardiovascular mortality. A cut-off of 11.4 IU/l
      identified patients with a higher mortality during follow-up. CONCLUSION: Rising
      PAPP-A levels are prognostic in patients with CAD. PAPP-A levels were especially
      predictive in ACS patients with troponin below 10% CV of the 99 th percentile for
      cardiovascular mortality.

PMID- 26223810
TI  - Late Nailfold Videocapillaroscopy Pattern Associated With Hand Calcinosis and
      Acro-Osteolysis in Systemic Sclerosis.
AB  - OBJECTIVE: To determine whether calcinosis and acro-osteolysis are related to
      specific nailfold videocapillaroscopy (NVC) features in patients with systemic
      sclerosis (SSc; scleroderma). METHODS: NVC and bilateral hand radiographs were
      systematically performed in 155 consecutively recruited patients with SSc during
      a 24-month period. Radiologic assessment of calcinosis and acro-osteolysis was
      performed blinded for the results on NVC features. RESULTS: Patients with
      calcinosis (n = 29) or acro-osteolysis (n = 25) on radiographs were more likely
      to have the late pattern on NVC, defined by severe loss of capillaries and
      neoangiogenesis (P = 0.003 and P < 0.001, respectively). A reduced number of
      capillaries was significantly found in patients with calcinosis (mean +/- SD 3.55
      +/- 1.76 versus 5.53 +/- 2.32 capillaries per finger; P < 0.001) and acro
      osteolysis (mean +/- SD 2.88 +/- 1.30 versus 5.60 +/- 2.26 capillaries per
      finger; P < 0.001). In addition, neoangiogenesis was more frequently observed in
      patients with severe acro-osteolysis (P = 0.021). Multivariate logistic
      regression analysis confirmed the independent association between the late NVC
      pattern and calcinosis (odds ratio [OR] 3.04, 95% confidence interval [95% CI]
      1.20-7.68) or acro-osteolysis (OR 4.57, 95% CI 1.66-12.55), together with history
      of and/or active digital ulcers. CONCLUSION: Acro-osteolysis and calcinosis are
      independently associated with the late NVC pattern and particularly with severe
      capillary loss. These results strengthen the link between these radiographic
      lesions and digital destructive vasculopathy. Moreover, severe acro-osteolysis
      was more likely to occur with neoangiogenesis, which may suggest an attempt to
      compensate bone resorption. Further studies are now needed to better understand
      the physiopathology of calcinosis and acro-osteolysis and determine whether any
      agent may modify the course of these lesions by influencing vessel damages.

PMID- 26223811
TI  - Inhibitory effects of advanced glycation end-products and Porphyromonas
      gingivalis lipopolysaccharide on the expression of osteoblastic markers of rat
      bone marrow cells in culture.
AB  - BACKGROUND AND OBJECTIVES: Diabetes is a major risk factor for periodontitis and
      there is a close relationship between the degree of hyperglycemia and the
      severity of periodontitis. Advanced glycation end-products (AGEs) accumulate in
      various tissues under diabetic conditions. AGEs in the periodontal tissues
      probably play a role in upregulating periodontal inflammation; however, the
      association of AGEs with the severity of periodontitis has not been fully
      clarified. Lipopolysaccharide from Porphyromonas gingivalis (P-LPS) is a potent
      pathogenic factor in periodontitis. Although the independent effect of AGE or P
      LPS on osteoblastic cells has been reported in vitro, the effect of adding both
      has not been clearly elucidated. In this study, to explore factors aggravating
      diabetic periodontitis, we investigated the effects of AGE and P-LPS on the
      expression of osteoblastic markers and the expression of inflammation-related
      markers in vitro. MATERIAL AND METHODS: Rat bone marrow cells were cultured, and
      alkaline phosphatase activity and bone nodule formation were evaluated as
      osteoblastic markers. Reverse transcription-polymerase chain reaction was
      performed to determine the mRNA expression of molecules associated with bone and
      inflammation. Protein levels of osteocalcin and interleukin-1beta (IL-1beta) were
      measured using enzyme-linked immunosorbent assay. RESULTS: AGEs and P-LPS
      independently reduced alkaline phosphatase activity and bone nodule formation.
      The addition of both AGE and P-LPS (AGE+P-LPS) further decreased these markers.
      Reverse transcription-polymerase chain reaction analysis revealed that AGE+P-LPS
      markedly decreased the mRNA expression of osteoblast-related molecules such as
      type 1 collagen, osteocalcin and Cbfa1, and markedly increased that of
      inflammation-related molecules such as IL1beta and S100A8. AGE and P-LPS
      decreased the protein level of osteocalcin and increased that of IL-1beta, and a
      further increase of IL-1beta was detected for AGE+P-LPS. CONCLUSION: AGEs and P
      LPS inhibited the expression of osteoblastic markers and increased the levels of
      inflammatory markers in rat bone marrow cells, suggesting that both AGE and P-LPS
      may be important factors associated with the aggravation of diabetic
      periodontitis.

PMID- 26223812
TI  - A proposal for a new classification of T4 breast cancer as stage IIIC: a report
      from the Korean Breast Cancer Society.
AB  - The objective of this study is to investigate staging system of the stage IIIB
      and stage IIIC Breast cancer and determine the criteria for an update of the
      classification system. Since AJCC 6th edition, it is pointed out that stage IIIB
      showed a worse outcome compared with stage IIIC. Using information from two
      databases, including the nationwide Korean Breast Cancer Registry (KBCR), three
      cohorts composed of patients from the Asan Medical Center from 1989 to 2002
      (cohort I), from 2003 to 2008 (cohort II), and KBCR from 2003 to 2005 (cohort
      III) were assembled. New classifications were suggested that rearranged stage
      IIIB as T1-3N3 disease and stage IIIC as T4 any N disease. From the joint
      analysis of 9640, invasive breast cancer patients from cohorts I and II showed
      the stage IIIB group showed a significantly worse DFS (HR 10.4, 95% CI 6.9-15.7)
      compared with the stage IIIC group (HR 7.2, 95% CI 5.9-8.7). T4d breast cancer
      showed worse DFS than T4 abc breast cancer but not significant (p = 0.505). The
      survival of patients with T1N3 and T2N3 tumors was higher than the other groups,
      and patients with T4N3 tumors showed the worst survival outcomes in terms of DFS,
      CSS. Using new suggested classification, in cohort III, the stage IIIB HR for CSS
      was changed from 15.4 (95% CI 10.6-22.1) in the AJCC 6th edition to 12.6 (95% CI
      10.1-15.6) in the proposed new staging system. The stage IIIC HR for CSS was
      changed from 13.3 (95% CI 10.7-16.4) in the AJCC 6th edition to 18.9 (95% CI 14.0
      25.6) in the proposed new staging using stage I as a reference. Reclassification
      of T4 any N disease as stage IIIC and T1-3N3 disease as stage IIIB is
      appropriate.

PMID- 26223813
TI  - Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell
      lines.
AB  - Heat shock factor 1 (HSF1) has long been recognized as the master transcription
      factor that regulates heat shock proteins (HSPs).  More recently HSF1 has been
      associated with a broader role in regulating response to a variety of cellular
      stresses beyond heat-shock.  We previously found that high HSF1 expression is
      associated with poor outcome in lung, breast and colon cancers. Importantly,
      however, the HSF1 signature correlated with poor outcome in these studies was not
      related to the heat shock response, which suggested that tumor outcome associated
      with high HSF expression may be due to processes other than stress response.
      Hence, we explored the question whether high HSF1 expression might be associated
      with the cancer stem cell (CSC) phenotype. To do so, we examined the association
      of HSF1 with CSC phenotype by FACS and immunofluorescence. In addition, we
      evaluated the effects of HSF1 over-expression and knock-down on sphere formation
      and CSC marker expression in breast cancer cell lines. Here, we report results
      demonstrating that high HSF1 not only correlates with CSC marker expression, but
      inducible HSF1 over-expression augments and HSF1 knock-down inhibits CSC
      phenotype. Furthermore, HSF1 expression confers resistance to chemotherapeutic
      drugs and increases CSC frequency. In conclusion, our study indicates that one of
      the potential HSP-independent HSF1 driven mechanisms that may contribute to poor
      outcome in human tumors involves regulation of the CSC phenotype. Hence,
      therapeutic inhibition of HSF1 may be one route to target CSCs in human tumors. 

PMID- 26223814
TI  - Assessment of HER2 status in invasive breast cancers with increased centromere 17
      copy number.
AB  - This study was designed to evaluate usefulness of additional fluorescence in situ
      hybridization (FISH) using other reference genes on chromosome 17 for assessment
      of HER2 status in invasive breast cancers with increased centromere 17 copy
      number, and to compare this approach with conventional methods based on the 2007
      and 2013 ASCO/CAP guidelines. We performed FISH with probes for SMS, RARA, and
      TP53 on 253 breast cancers with centromeric probe CEP17 copy number >= 2.6 using
      tissue microarrays. If one or more gene had a mean copy number <2.6, the largest
      number for that gene(s) was chosen as an alternative to CEP17 copy number. Of the
      243 cases in which re-grading was possible, only 2 had copy numbers >= 2.6 for
      RARA, SMS, and TP53. Of the 151 breast cancers which were considered HER2 non
      amplified by the 2007 ASCO/CAP guidelines using the HER2:CEP17 ratio, 42 (27.8%)
      were re-graded as amplified and 33 (21.8%) as equivocal after FISH using
      additional reference genes. Of the 101 HER2-non-amplified cases by the 2013
      ASCO/CAP guidelines, 2 (2.0%) were reclassified as amplified and 24 (23.8%) as
      equivocal. Of 46 equivocal cases, 35 (76.1%) were re-graded as amplified. After
      re-grading, HER2-amplified cases were significantly increased, and the
      concordance between HER2 FISH and HER2 immunohistochemistry decreased. And some
      pathologic features of the cases which were designated to have HER2 amplification
      after additional FISH were not compatible with those of HER2-amplified breast
      cancers. The use of additional reference genes has been suggested as an option
      for accurate assessment of HER2 status in breast cancers with increased CEP17
      copy number. However, this has limitations in that it can cause over-grading of
      HER2 status in tumors that lose the new reference genes. Thus, at present, it
      seems that additional FISH using other reference gene such as SMS, RARA, and TP53
      for the cases with increased CEP17 copy number is not suitable for daily
      practice.

PMID- 26223815
TI  - Proteomics of ionomycin-induced ascidian sperm reaction: Released and exposed
      sperm proteins in the ascidian Ciona intestinalis.
AB  - Sperm proteins mediating sperm-egg interaction should be exhibited on the sperm
      surface, or exposed or released when sperm approach an egg. In ascidians
      (protochordates), sperm undergo a sperm reaction, characterized by enhanced sperm
      motility and mitochondrial swelling and shedding on contact with the vitelline
      coat (VC) or by treatment with Ca(2+) ionophore. Here, proteomic analysis was
      conducted on sperm exudates and sperm surface proteins using ionomycin-induced
      sperm reaction and cell-impermeable labeling in Ciona intestinalis type A (C.
      robusta). In the exudate from sperm treated with ionomycin, membrane proteins
      including a possible VC receptor CiUrabin were abundant, indicating the release
      of membranous compartments during sperm reaction. Among the surface proteins
      XP_009859314.1 (uncharacterized protein exhibiting homology to HrTTSP-1) was most
      abundant before the sperm reaction, but XP_004227079.1 (unknown Ig superfamily
      protein) appears to be most abundantly exposed by the sperm reaction. Moreover,
      proteins containing a notable set of domains, astacin-like metalloprotease domain
      and thrombospondin type 1 repeat(s), were found in this fraction. Possible roles
      in fertilization as well as localizations and behaviors of these proteins are
      discussed. 

PMID- 26223816
TI  - Quality standards for bone conduction implants.
AB  - CONCLUSION: Bone conduction implants are useful in patients with conductive and
      mixed hearing loss for whom conventional surgery or hearing aids are no longer an
      option. They may also be used in patients affected by single-sided deafness.
      OBJECTIVES: To establish a consensus on the quality standards required for
      centers willing to create a bone conduction implant program. METHOD: To ensure a
      consistently high level of service and to provide patients with the best possible
      solution the members of the HEARRING network have established a set of quality
      standards for bone conduction implants. These standards constitute a realistic
      minimum attainable by all implant clinics and should be employed alongside
      current best practice guidelines. RESULTS: Fifteen items are thoroughly analyzed.
      They include team structure, accommodation and clinical facilities, selection
      criteria, evaluation process, complete preoperative and surgical information,
      postoperative fitting and assessment, follow-up, device failure, clinical
      management, transfer of care and patient complaints.

PMID- 26223818
TI  - Pulmonary high-resolution ultrashort TE MR imaging: Comparison with thin-section
      standard- and low-dose computed tomography for the assessment of pulmonary
      parenchyma diseases.
AB  - BACKGROUND: To determine the accuracy of pulmonary MR imaging with ultrashort
      echo time (UTE) for lung and mediastinum assessments using computed tomography
      (CT) as the reference standard, for various pulmonary parenchyma diseases.
      METHODS: Eight-five consecutive patients (46 males: mean age, 69 years and 39
      females: mean age, 69 years) with various pulmonary parenchyma diseases were
      examined with chest standard- and low-dose CTs and pulmonary MR imaging with UTE.
      This was followed by visual assessment using a 5-point system of the presence of
      nodules or masses, ground-glass opacity, micronodules, nodules, patchy shadow or
      consolidation, emphysema or bullae, bronchiectasis, reticular opacity, and
      honeycomb and traction bronchiectasis. Presence of aneurysms, pleural or
      pericardial effusions, pleural thickening or tumor, and lymph adenopathy was also
      evaluated using a 5-point system. To compare the capability of the methods for
      lung parenchyma and mediastinum evaluation, intermethod agreement was evaluated
      by means of kappa statistics and chi2 test. Receiver operating characteristic
      analyses were used to compare diagnostic performance of all methods. RESULTS:
      Intermethod agreements between pulmonary MR imaging and standard-dose and low
      dose CT were significant and either substantial or almost perfect (0.67 <= kappa
      <= 0.98; P < 0.0001). Areas under the curve for emphysema or bullae,
      bronchiectasis or traction bronchiectasis and reticular opacity on standard-dose
      CT were significantly larger than those on low-dose CT (emphysema or bullae: P =
      0.0002; reticular opacity: P < 0.0001) and pulmonary MR imaging (emphysema or
      bullae: P < 0.0001; bronchiectasis: P = 0.008; reticular opacity: P < 0.0001).
      CONCLUSION: Pulmonary MR imaging with UTE is useful for lung and mediastinum
      assessment and evaluation of radiological findings for patients with various
      pulmonary parenchyma diseases.

PMID- 26223817
TI  - Controlled release of an anthrax toxin-neutralizing antibody from hydrolytically
      degradable polyethylene glycol hydrogels.
AB  - In this study, hydrophilic and hydrolytically degradable poly (ethylene glycol)
      (PEG) hydrogels were formed via Michael-type addition and employed for sustained
      delivery of a monoclonal antibody against the protective antigen of anthrax.
      Taking advantage of the PEG-induced precipitation of the antibody, burst release
      from the matrix was avoided. These hydrogels were able to release active
      antibodies in a controlled manner from 14 days to as long as 56 days in vitro by
      varying the polymer architectures and molecular weights of the precursors.
      Analysis of the secondary and tertiary structure and the in vitro activity of the
      released antibody showed that the encapsulation and release did not affect the
      protein conformation or functionality. The results suggest the promise for
      developing PEG-based carriers for sustained release of therapeutic antibodies
      against toxins in various applications.

PMID- 26223819
TI  - Dual roles of endogenous and exogenous galectin-1 in the control of testicular
      immunopathology.
AB  - Galectin-1 (Gal-1), a proto-type member of galectin family, is highly expressed
      in immune privileged sites, including the testis. However, in spite of
      considerable progress the relevance of endogenous and exogenous Gal-1 in testis
      pathophysiology have not yet been explored. Here we evaluated the in vivo roles
      of Gal-1 in experimental autoimmune orchitis (EAO), a well-established model of
      autoimmune testicular inflammation associated with subfertility and infertility.
      A significant reduction in the incidence and severity of EAO was observed in mice
      genetically deficient in Gal-1 (Lgals1(-/-)) versus wild-type (WT) mice.
      Testicular histopathology revealed the presence of multifocal testicular damage
      in WT mice characterized by an interstitial mononuclear cell infiltrate and
      different degrees of germ cell sloughing of seminiferous tubules. TUNEL assay and
      assessment of active caspase-3 expression, revealed the prevalence of apoptotic
      spermatocytes mainly localized in the adluminal compartment of seminiferous
      tubules in EAO mice. A significant increased number of TUNEL-positive germ cells
      was detected in EAO testis from WT compared with Lgals1(-/-) mice. In contrast,
      exogenous administration of recombinant Gal-1 to WT mice undergoing EAO
      attenuated the severity of the disease. Our results unveil a dual role of
      endogenous versus exogenous Gal-1 in the control of autoimmune testis
      inflammation. 

PMID- 26223820
TI  - Electrostatic Localization of RNA to Protocell Membranes by Cationic Hydrophobic
      Peptides.
AB  - Cooperative interactions between RNA and vesicle membranes on the prebiotic earth
      may have led to the emergence of primitive cells. The membrane surface offers a
      potential platform for the catalysis of reactions involving RNA, but this
      scenario relies upon the existence of a simple mechanism by which RNA could
      become associated with protocell membranes. Here, we show that electrostatic
      interactions provided by short, basic, amphipathic peptides can be harnessed to
      drive RNA binding to both zwitterionic phospholipid and anionic fatty acid
      membranes. We show that the association of cationic molecules with phospholipid
      vesicles can enhance the local positive charge on a membrane and attract RNA
      polynucleotides. This phenomenon can be reproduced with amphipathic peptides as
      short as three amino acids. Finally, we show that peptides can cross bilayer
      membranes to localize encapsulated RNA. This mechanism of polynucleotide
      confinement could have been important for primitive cellular evolution. 

PMID- 26223821
TI  - Allowing Physicians to Choose the Value of Compensation for Participation in a
      Web-Based Survey: Randomized Controlled Trial.
AB  - BACKGROUND: Survey response rates among physicians are declining, and determining
      an appropriate level of compensation to motivate participation poses a major
      challenge. OBJECTIVE: To estimate the effect of permitting intensive care
      physicians to select their preferred level of compensation for completing a short
      Web-based survey on physician (1) response rate, (2) survey completion rate, (3)
      time to response, and (4) time spent completing the survey. METHODS: A total of
      1850 US intensivists from an existing database were randomized to receive a
      survey invitation email with or without an Amazon.com incentive available to the
      first 100 respondents. The incentive could be instantly redeemed for an amount
      chosen by the respondent, up to a maximum of US $50. RESULTS: The overall
      response rate was 35.90% (630/1755). Among the 35.4% (111/314) of eligible
      participants choosing the incentive, 80.2% (89/111) selected the maximum value.
      Among intensivists offered an incentive, the response was 6.0% higher (95% CI 1.5
      10.5, P=.01), survey completion was marginally greater (807/859, 94.0% vs
      892/991, 90.0%; P=.06), and the median number of days to survey response was
      shorter (0.8, interquartile range [IQR] 0.2-14.4 vs 6.6, IQR 0.3-22.3; P=.001),
      with no difference in time spent completing the survey. CONCLUSIONS: Permitting
      intensive care physicians to determine compensation level for completing a short
      Web-based survey modestly increased response rate and substantially decreased
      response time without decreasing the time spent on survey completion.

PMID- 26223822
TI  - The role of personal models in clinical management: Exploring health care
      providers' beliefs about psoriasis.
AB  - OBJECTIVES: Individuals' illness representations, including beliefs about
      psoriasis (a complex immune-mediated condition), and their emotional responses to
      the condition guide self-management behaviour. It is also plausible that health
      care providers' illness representations guide their own management of psoriasis.
      Patients commonly report poor health care experiences related to psoriasis, and
      the role of health care providers' beliefs, emotions, as well as their knowledge,
      experiences and behaviours ('personal models') in this is unexplored. This study
      aimed explore health care providers' personal models of psoriasis. DESIGN AND
      METHODS: Qualitative analysis of 23 semi-structured interviews with health care
      professionals providing care for psoriasis patients was performed. Purposive
      sampling achieved maximum variation regarding participant discipline, level of
      experience, gender and age. The self-regulatory/common sense model informed data
      collection and initial data analysis. Principles of framework analysis were used
      to generate predetermined and emergent key issues related to practitioners'
      personal models. RESULTS: Three types of personal model emerged. Sophisticated
      Linear Model: 70% of practitioners recognized psoriasis as a complex condition
      but managed it as a skin condition. Mixed Model: 17% of practitioners
      recognized/managed some elements of psoriasis as complex and some as a skin
      condition. Sophisticated-Sophisticated Model: 13% recognized and managed
      psoriasis as a complex condition. Across the data set, five themes emerged
      illustrating key patterns underpinning these different models including (1)
      Recognising complexity, (2) Putting skin first, (3) Taking on the complexities of
      psoriasis with the patient, (4) Aiming for clearance, and (5) Affective
      experiences within psoriasis consultations. CONCLUSIONS: Health care providers
      recognized psoriasis as a complex condition but commonly reported managing
      psoriasis as a simple skin condition. Providers' beliefs and management
      approaches varied in the extent to which they were consistent with one another;
      and their emotional experiences during consultations may vary depending upon
      their personal model. Findings could inform future dermatology training
      programmes by highlighting the role of health care providers' illness
      representations in clinical management of the condition. STATEMENT OF
      CONTRIBUTION: What is already known on this subject? Health behaviour is
      predicted by underlying beliefs and emotions associated with an illness and its
      treatment. Few studies have examined health care providers' beliefs and emotions
      about the illnesses they manage in clinical practice. Many patients are
      dissatisfied with dermatology consultations and wish to be treated holistically.
      What does this study add? Qualitative exploration of health care providers'
      beliefs/emotions revealed their personal models of psoriasis. Providers' personal
      models of psoriasis vary in coherence and are often skin rather than whole person
      focused. Further investigation of health care providers' models of psoriasis and
      their impact on health outcomes is needed.

PMID- 26223824
TI  - Rural-urban difference in female breast cancer diagnosis in Missouri.
AB  - INTRODUCTION: The stage at cancer diagnosis has a tremendous impact on type of
      treatment, recovery and survival. In most cases the earlier the cancer is
      detected and treated the higher the survival rate for the patient. The purpose of
      this study was to examine the impact of spatial access to healthcare services on
      late detection of female breast cancer diagnosis in Missouri, taking into account
      access and distance to the nearest mammography center and/or hospital. METHODS:
      This was a cross-sectional retrospective study of female breast cancer diagnosis
      in different geographic regions of Missouri. The sample was restricted to
      Missouri women diagnosed with breast cancer, whose cases had been reported to the
      Missouri Cancer Registry and Research Center between 2003 and 2008. A geographic
      information system network analysis was used to calculate distance traveled by
      road from the centroid of each county to the nearest healthcare facility.
      RESULTS: A total of 28 536 cases of female breast cancers were reported to the
      Missouri Cancer Registry and Research Center between 2003 and 2008. Of these 25
      743 (90.2%) were Caucasian (white) while 2793 (9.8%) were African-American
      (black). Analysis showed that the proportion of African-Americans with late-stage
      detection exceeded that of whites in almost all rural and urban locations. From
      2003 to 2005 more than 50% of all late-stage diagnoses of African-American women
      occurred in metropolitan (metro) medium (55.6%) and completely rural counties
      (66.7%). Other locations recorded a smaller number of late-stage detection among
      African-American women: metro small (42.3%), urban large (47.4%) and urban small
      (44.9%) counties. Most of the late-stage diagnoses of white women were reported
      in urban small (32.2%) and rural (32.3%) counties. Between 2006 and 2008, again,
      the proportion of late-stage diagnoses among black women was the highest. Access
      to hospitals is fairly distributed among all counties. Women from disadvantaged
      non-metro areas have the same level of access to hospitals as those in metro
      areas within a travel time of 15 to 30 minutes. However, although there are
      almost 180 mammography screening centers across the state, access to these
      services is not evenly distributed. A network analysis of the closest facility of
      the type showed that women living in 19 non-metro rural counties have to travel
      more than 45 minutes one way by car for mammography services. Thirteen of the 19
      counties are classified as completely rural. CONCLUSIONS: Women with breast
      cancer living in areas with limited access to healthcare services are more likely
      to have been diagnosed with late-stage breast cancer.

PMID- 26223825
TI  - Effect of Mesoporous Structured Cathode Materials on Charging Potentials and Rate
      Capability of Lithium-Oxygen Batteries.
AB  - Solid and nonconductive discharge products that form on the cathode of Li-O2
      batteries are difficult to decompose efficiently into Li(+) and O2 during
      charging, which induces a high overcharge potential, low energy efficiency, and
      poor cyclability. In this paper, we investigated the effects of the mesoporous
      structure on the morphology of the discharge products, the capacities of the
      cells, and the discharging/charging potentials. To isolate the effect of the
      mesostructures, mesoporous carbons, CMK-3 and MSU-F-C, were used without the
      addition of other electrocatalysts. The discharge products were confined within
      the pores. Consequently, the charging potentials were decreased owing to small
      and amorphous lithium oxides. The large, 3 D interconnected pores of MSU-F-C
      lowered the charging potentials at a high current density and increased the rate
      capabilities relative to the parameters found for the small pores of CMK-3. These
      results demonstrate that control of the porous structure is necessary to enhance
      the performance of Li-O2 batteries. 

PMID- 26223826
TI  - Sarcopenia is a risk factor for the recurrence of hepatocellular carcinoma after
      curative treatment.
AB  - BACKGROUND AND AIM: Sarcopenia, initially proposed as decreased of muscle mass
      and strength, is associated with aging and malignant diseases. The aim of the
      present study was to determine whether there is a correlation between sarcopenia
      and the recurrence of hepatocellular carcinoma (HCC) after curative treatment.
      METHODS: We conducted a retrospective analysis of consecutive naive patients with
      HCC who underwent curative resection or radiofrequency ablation. To eliminate the
      influence of cause or the severity of liver damage, subjects were limited to
      those with HCC with hepatitis C-related cirrhosis and Child-Pugh class A liver
      function. Patients were assessed using computed tomographic measurement of muscle
      mass at the level of the third lumbar (L3) vertebrae, the L3 skeletal muscle
      index (L3 SMI). Sarcopenia was defined by using previously published, sex
      specific cut-off value. RESULTS: Sarcopenia was present in 61 of 92 patients.
      Patients' median age was 71.5 years (range, 47-84), and the baseline
      characteristics of patients were comparable between patients with and without
      sarcopenia except for sex, serum albumin level, prothrombin time, diabetes
      mellitus and body mass index. Recurrence rates at 1, 3 and 5 years were
      39.1%,77.1%,81.7% for patients with sarcopenia and 23.5%,59.5% and 75.7% for
      patients without sarcopenia, respectively (P = 0.03). Multivariate Cox analysis
      revealed that sarcopenia and preoperative alpha-fetoprotein of more than 40 ng/mL
      were significant independent factors for recurrence. CONCLUSION: Sarcopenia is a
      risk factor for recurrence in patients with HCC who were treated with curative
      treatment.

PMID- 26223827
TI  - Distribution of Ventricular Fibrosis Associated With Life-Threatening Ventricular
      Tachyarrhythmias in Patients With Nonischemic Dilated Cardiomyopathy.
AB  - BACKGROUND: Current guidelines recommend the implantation of an implantable
      cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death
      (SCD) in a subgroup of patients with nonischemic cardiomyopathy (NICM) who have a
      left ventricular ejection fraction (LVEF) <= 30-35%, and are NYHA functional
      class II or III. However, the majority of patients with an ICD implantation for
      primary prevention did not receive appropriate ICD therapy. The purpose of this
      study was to evaluate the association between myocardial fibrosis detected by
      cardiovascular magnetic resonance (CMR) imaging and life-threatening ventricular
      arrhythmic events in NICM patients. METHODS: One hundred and seventy-five NICM
      patients with an LVEF ? 35 % and NYHA functional class II or III, (60 +/- 15
      years, LVEF 29 +/- 5.4%) were studied. Myocardial fibrosis was identified with a
      late gadolinium enhancement (LGE) on CMR. Clinical events were defined as SCD or
      life-threatening ventricular arrhythmic events and were followed up for 5.1 +/-
      3.3 years. RESULTS: The presence of an LGE was detected in 122 patients (70%). No
      life-threatening ventricular arrhythmia events occurred in patients with the
      absence of an LGE. A total of 18 ventricular tachycardia and 8 ventricular
      fibrillation events were found in patients with the presence of an LGE (P <
      0.01). Sensitivity, specificity, and positive and negative predictive value of
      LGE in predicting life-threatening ventricular arrhythmia events were 100%, 34%,
      and 15% and 100%, respectively. Multivariate analysis showed that the presence of
      both septal and lateral mid-wall LGE was associated with life-threatening
      ventricular arrhythmic events (hazard ratio 23.1 CI; 2.88-184.9, P = 0.003).
      CONCLUSIONS: The absence of an LGE predicts a low potential risk of SCD and life
      threatening ventricular arrhythmia events in the near future. CMR may be a useful
      tool for selecting suitable patients for primary ICD implantations in NICM
      patients.

PMID- 26223828
TI  - CT colonography: a survey of general practitioners' knowledge and interest.
AB  - PURPOSE: To verify the knowledge and interest of general practitioners on
      computed tomography colonography (CTC). MATERIALS AND METHODS: In 2014, a Web
      based questionnaire was proposed to all general practitioners of [Milan, Italy].
      The questionnaire consisted of ten questions concerning general practitioners'
      knowledge about CTC, including application of guidelines in clinical scenarios
      and diagnostic performance. RESULTS: Out of 1,053 general practitioners, 231
      (22%), 155 men and 76 women (mean age 58 years), completed the survey. We found a
      significant difference between the age of responders and that of non-responders
      (p = 0.0033). Of the 231 responders, 84% were aware of the possibility of using
      CTC as a method for examining the colon-rectum. However, only 57% were aware
      about low X-ray exposure delivered by CTC and about the possibility of using a
      reduced cleansing protocol. Only 48% were aware that CTC accuracy in diagnosing
      10-mm or larger polyps and colorectal cancers was similar to that of conventional
      colonoscopy, while 62% were informed about CTC advantages in comparison with
      double-contrast barium enema; 59% thought that CTC had a potential role as a
      screening test; 85-86% suggested CTC in the case of refused or incomplete
      conventional colonoscopy; 79% suggested immediate conventional colonoscopy in the
      case of at least one 10-mm polyp. About 54% usually prescribe one CTC every 4-6
      months, while 36% never have, 3% one CTC per month, and 7% one every 2-3 months.
      Ninety-four per cent declared that they were willing to attend a course on CTC.
      CONCLUSION: General practitioners have limited knowledge concerning CTC.
      Radiological societies should fill this gap offering dedicated educational
      initiatives.

PMID- 26223829
TI  - Structural mechanism of complex assemblies: characterisation of beta
      lactoglobulin and pectin interactions.
AB  - Knowledge of how proteins and polysaccharides interact is the key to
      understanding encapsulation and emulsification in these composite systems and
      ultimately to understanding the structures of many biological network systems. As
      a model system we have studied beta-lactoglobulin A (betaLgA) interacting with
      pectins of various amounts and distribution patterns of charge. The studies were
      conducted at pH 4 at minimal ionic strength, where the betaLgA and the pectins
      are oppositely charged, resulting in an electrostatic attraction to each other.
      Isothermal titration calorimetry (ITC) experiments were performed to determine
      the thermodynamics associated with betaLgA-pectin titration. It was found that
      betaLgA only interacted with pectins with an adequate amount of charge, and that
      the complexation between betaLgA and pectin was a two-step process initially
      involving binding of the protein to available sites on the pectin, and
      subsequently binding of the protein onto the bound protein that has previously
      adsorbed. Circular dichroism (CD) and intrinsic tryptophan fluorescence were also
      measured of betaLgA during its interaction with the pectin samples, and show that
      the binding leads to significant conformational changes in betaLgA. An increase
      in the turbidity of the solution of the resultant complexes indicates the
      formation of large-scale interpolymer associations of the primary complexes
      mediated by protein-rich domains. 

PMID- 26223830
TI  - Borohydride Ionic Liquids as Hypergolic Fuels: A Quest for Improved Stability.
AB  - Hydrazine and its derivatives are used as fuels in rocket propellant systems;
      however, due to high vapor pressure, toxicity, and carcinogenicity, handling of
      such compounds is extremely hazardous. Hypergolic ionic liquids have shown great
      promise to become viable replacements for hydrazines as fuels. Borohydride
      containing ionic liquids have now been synthesized using a more efficient
      synthetic pathway that does not require liquid ammonia and halide precursors.
      Among the eight new compounds, 1-allyl-3-n-butyl-imidazolium borohydride (1) and
      1, 3-diallylimidazolium borohydride (5) exhibit very short ignition-delay times
      (ID) of 8 and 3 ms, respectively. The hydrolytic stability of borohydride
      compounds has been greatly improved by attaching long-chain alkyl substituents to
      the imidazole ring. 1,3-Di-(n-octyl)-imidazolium borohydride (3) is a water
      stable borohydride-containing ionic liquid. 1,3-Di-(n-butyl)-imidazolium
      borohydride (2) is a unique example of a borohydride liquid crystal. These ionic
      liquids have some unusual advantages, including negligible vapor pressures, good
      ignition delay (ID) times, and reduced synthetic and storage costs, thereby
      showing good application potential as environmentally friendly fuels in
      bipropellant formulations. In addition, they also have potential applications in
      the form of reducing agents and hydrogen storage materials. 

PMID- 26223831
TI  - Benefits of Exercise Training in Multiple Sclerosis.
AB  - Exercise training represents a behavioral approach for safely managing many of
      the functional, symptomatic, and quality of life consequences of multiple
      sclerosis (MS). This topical review paper summarizes evidence from literature
      reviews and meta-analyses, supplemented by recent individual studies, indicating
      that exercise training can yield small but important improvements in walking,
      balance, cognition, fatigue, depression, and quality of life in MS. The paper
      highlights limitations of research on exercise training and its consequences and
      future research directions and provides an overview for promotion of exercise
      training in MS based on recent prescriptive guidelines. Collectively, the
      evidence for the benefits of exercise training in MS suggests that the time is
      ripe for the promotion of exercise by healthcare providers, particularly
      neurologists as a central part of the clinical care and management of MS
      patients. 

PMID- 26223832
TI  - Complicating Symmetric Peripheral Gangrene after Dopamine Therapy to Patients
      with Septic Shock.
AB  - Dopamine is commonly used as a first-line agent in the treatment of patients with
      septic shock. The use of dopamine rarely causes symmetric peripheral dry
      gangrene. If the symmetric peripheral dry gangrene occurs in the patient after
      dopamine injection, it easily leads to disagreement between doctors and patients.
      A 60-year-old woman who had sudden septic shock was sent to intensive care unit
      (ICU). She was received dopamine injection according to the routine during
      treatment. Over the next 3 months, her limbs developed to dry gangrene and
      required amputation. The result shows that the occurrence of dry gangrene could
      only be associated with the long-term excessive use of dopamine according to the
      medical records. Although dopamine is a conventional drug for the treatment of
      septic shock, the forensic workers and clinicians must realize that vasopressors
      such as dopamine have been implicated directly or as a contributory cause in dry
      gangrene cases.

PMID- 26223833
TI  - The effect of ladder-climbing exercise on atrophy/hypertrophy-related myokine
      expression in middle-aged male Wistar rats.
AB  - We investigated the change in myokine expression related to hypertrophy (IL-4, IL
      6, IL-10) and atrophy (TNF-alpha, NFkappaB, IL-1beta) in middle-aged rats after
      resistance exercise with ladder climbing. 50- and 10-week-old male Wistar rats
      were randomly assigned to two groups: the sedentary and exercise groups. The
      exercise groups underwent a ladder-climbing exercise for 8 weeks. While the
      tibialis anterior muscle mass in the young group significantly increased after
      the ladder-climbing exercise, the middle-aged group did not show any changes
      after undergoing the same exercise. To understand the molecular mechanism causing
      this difference, we analyzed the change in hypertrophy- and atrophy-related
      myokine levels from the tibialis anterior muscle. After 8 weeks of ladder
      climbing exercise, the IL-4 and IL-10 protein levels did not change. However, the
      IL-6 level significantly increased after exercise training, but the amount of
      increase in the young training group was higher than in the middle-aged training
      group. IL-1beta and TNF-alpha as well as NFkappaB protein levels were
      significantly higher in the middle-aged group than in the young group. Except for
      TNF-alpha, exercise training did not affect IL-1beta and NFkappaB protein levels.
      The TNF-alpha level significantly decreased in the middle-aged exercise training
      group. AMPK and PGC-1alpha levels also significantly increased after exercise
      training, but there was no difference between age-related groups. Therefore, 8
      week high-intensity exercise training using ladder climbing downregulates the
      skeletal muscle production of myokine involved in atrophy and upregulates
      hypertrophic myokine. However, the extent of these responses was lower in the
      middle-aged than young group.

PMID- 26223834
TI  - Laparoscopic versus open distal gastrectomy for early gastric cancer in Japan:
      long-term clinical outcomes of a randomized clinical trial.
AB  - PURPOSE: We report the long-term clinical outcomes of a randomized clinical trial
      comparing laparoscopy-assisted distal gastrectomy (LADG) with open DG (ODG).
      METHODS: Between 2005 and 2008, 63 patients with clinical T1 (cT1) gastric cancer
      were randomly assigned to undergo either LADG or ODG. Long-term clinical outcomes
      included prospective questionnaire-based symptoms and survival. RESULTS: Based on
      the responses to the prospective questionnaires, patients who underwent LADG
      reported greater satisfaction and were more likely to favor the procedure than
      those who underwent ODG. The most notable difference in symptoms was related to
      wound pain and diarrhea. After ODG, wound pain reduced in intensity but persisted
      throughout the follow-up. Surprisingly, diarrhea was more frequent after LADG
      than after ODG, possibly due to overeating, because symptoms elicited by
      overeating, such as vomiting after a meal or heartburn, were also more frequent
      after LADG. In terms of long-term survival, there were no cases of recurrence in
      either group. CONCLUSIONS: LADG was associated with less wound pain during long
      term follow-up after surgery, whereas symptoms related to overeating were common.
      Based on our findings and the patients' reported satisfaction, we recommend LADG
      for cT1 gastric cancer as an effective procedure with excellent long-term
      survival.

PMID- 26223835
TI  - The extracellular matrix molecule brevican is an integral component of the
      machinery mediating fast synaptic transmission at the calyx of Held.
AB  - KEY POINTS: The proteoglycan brevican is a major component of the extracellular
      matrix of perineuronal nets and is highly enriched in the perisynaptic space
      suggesting a role for synaptic transmission. We have introduced the calyx of Held
      in the auditory brainstem as a model system to study the impact of brevican on
      dynamics and reliability of synaptic transmission. In vivo extracellular single
      unit recordings at the calyx of Held in brevican-deficient mice yielded a
      significant increase in the action potential (AP) transmission delay and a
      prolongation of pre- and postsynaptic APs. The changes in dynamics of signal
      transmission were accompanied by the reduction of presynaptic vGlut1 and
      ultrastructural changes in the perisynaptic space. These data show that brevican
      is an important mediator of fast synaptic transmission at the calyx of Held.
      ABSTRACT: The extracellular matrix is an integral part of the neural tissue. Its
      most conspicuous manifestation in the brain are the perineuronal nets (PNs) which
      surround somata and proximal dendrites of distinct neuron types. The chondroitin
      sulfate proteoglycan brevican is a major component of PNs. In contrast to other
      PN-comprising proteoglycans (e.g. aggrecan and neurocan), brevican is mainly
      expressed in the perisynaptic space closely associated with both the pre- and
      postsynaptic membrane. This specific localization prompted the hypothesis that
      brevican might play a role in synaptic transmission. In the present study we
      specifically investigated the role of brevican in synaptic transmission at a
      central synapse, the calyx of Held in the medial nucleus of the trapezoid body,
      by the use of in vivo electrophysiology, immunohistochemistry, biochemistry and
      electron microscopy. In vivo extracellular single-unit recordings were acquired
      in brevican-deficient mice and the dynamics and reliability of synaptic
      transmission were compared to wild-type littermates. In knockout mice, the speed
      of pre-to-postsynaptic action potential (AP) transmission was reduced and the
      duration of the respective pre- and postsynaptic APs increased. The reliability
      of signal transmission, however, was not affected by the lack of brevican. The
      changes in dynamics of signal transmission were accompanied by the reduction of
      (i) presynaptic vGlut1 and (ii) the size of subsynaptic cavities. The present
      results suggest an essential role of brevican for the functionality of high-speed
      synaptic transmission at the calyx of Held.

PMID- 26223837
TI  - Regional gastrointestinal transit and pH studied in 215 healthy volunteers using
      the wireless motility capsule: influence of age, gender, study country and
      testing protocol.
AB  - BACKGROUND: The wireless motility capsule (WMC) offers the ability to investigate
      luminal gastrointestinal (GI) physiology in a minimally invasive manner. AIM: To
      investigate the effect of testing protocol, gender, age and study country on
      regional GI transit times and associated pH values using the WMC. METHODS:
      Regional GI transit times and pH values were determined in 215 healthy volunteers
      from USA and Sweden studied using the WMC over a 6.5-year period. The effects of
      test protocol, gender, age and study country were examined. RESULTS: For GI
      transit times, testing protocol was associated with differences in gastric
      emptying time (GET; shorter with protocol 2 (motility capsule ingested
      immediately after meal) vs. protocol 1 (motility capsule immediately before):
      median difference: 52 min, P = 0.0063) and colonic transit time (CTT; longer with
      protocol 2: median 140 min, P = 0.0189), but had no overall effect on whole gut
      transit time. Females had longer GET (by median 17 min, P = 0.0307), and also
      longer CTT by (104 min, P = 0.0285) and whole gut transit time by (263 min, P =
      0.0077). Increasing age was associated with shorter small bowel transit time (P =
      0.002), and study country also influenced small bowel and CTTs. Whole gut and
      CTTs showed clustering of data at values separated by 24 h, suggesting that
      describing these measures as continuous variables is invalid. Testing protocol,
      gender and study country also significantly influenced pH values. CONCLUSIONS:
      Regional GI transit times and pH values, delineated using the wireless motility
      capsule (WMC), vary based on testing protocol, gender, age and country.
      Standardisation of testing is crucial for cross-referencing in clinical practice
      and future research.

PMID- 26223836
TI  - miRNA-133 augments coelomocyte phagocytosis in bacteria-challenged Apostichopus
      japonicus via targeting the TLR component of IRAK-1 in vitro and in vivo.
AB  - In this study, we explored the potential roles of miRNA-133 in regulating TLR
      pathways in the sea cucumber Apostichopus japonicus. Target screening of RNA-Seq
      data successfully identified interleukin-1 receptor-associated kinase (AjIRAK-1)
      as a putative target of miR-133. This result was further validated by negative
      expression profiles in Vibrio splendidus-challenged coelomocytes and
      lipopolysaccharide (LPS)-exposed cell cultures. HEK-293T cells transfected with a
      dual-luciferase reporter fused to the 3'UTR of wild-type or mutant AjIRAK-1
      exhibited a 52.9% reduction in luciferase activity (p < 0.01) compared to
      controls. Co-infection with a miR-133 mimics or a specific siRNA targeting AjIRAK
      1 significantly repressed the mRNA and protein expression levels of AjIRAK-1 and
      its downstream molecules, such as AjTRAF6 and Ajp105, in primary coelomocytes. In
      contrast, a miR-133 inhibitor significantly increased the expression of these TLR
      pathway members. The injection of miR-133 agomir or AjIRAK-1 siRNA into sea
      cucumbers not only decreased the expression of AjIRAK-1 and its downstream
      molecules but also significantly increased V. splendidus coelomocyte
      phagocytosis. All of the present data provide direct evidence that miR-133 is
      involved in TLR cascade modulation through AjIRAK-1 targeting to promote V.
      splendidus coelomocyte phagocytosis in these non-model invertebrates. 

PMID- 26223838
TI  - Avoiding prepositional pile-up.

PMID- 26223839
TI  - Epidemiological features and prognostic parameters of multiple primary melanomas
      in CDKN2A-mutations patients.

PMID- 26223841
TI  - Perinatal inflammation: a common factor in the early origins of cardiovascular
      disease?
AB  - Cardiovascular disease continues to be the leading cause of global morbidity and
      mortality. Traditional risk factors account for only part of the attributable
      risk. The origins of atherosclerosis are in early life, a potential albeit
      largely unrecognized window of opportunity for early detection and treatment of
      subclinical cardiovascular disease. There are robust epidemiological data
      indicating that poor intrauterine growth and/or prematurity, and perinatal
      factors such as maternal hypercholesterolaemia, smoking, diabetes and obesity,
      are associated with adverse cardiovascular intermediate phenotypes in childhood
      and adulthood. Many of these early-life risk factors result in a heightened
      inflammatory state. Inflammation is a central mechanism in the development of
      atherosclerosis and cardiovascular disease, but few studies have investigated the
      role of overt perinatal infection and inflammation (chorioamnionitis) as a
      potential contributor to cardiovascular risk. Limited evidence from human and
      experimental models suggests an association between chorioamnionitis and cardiac
      and vascular dysfunction. Early life inflammatory events may be an important
      mechanism in the early development of cardiovascular risk and may provide
      insights into the associations between perinatal factors and adult cardiovascular
      disease. This review aims to summarise current data on the early life origins of
      atherosclerosis and cardiovascular disease, with particular focus on perinatal
      inflammation. 

PMID- 26223842
TI  - Benefit of Earlier Anti-TNF Treatment on IBD Disease Complications?
AB  - BACKGROUND: Anti-tumour necrosis factor [anti-TNF] treatment was demonstrated to
      have disease-modifying abilities in inflammatory bowel disease [IBD]. In this
      study, we aimed to determine the effect of anti-TNF treatment timing on IBD
      disease complications and mucosal healing [MH]. METHODS: The following IBD
      related complications were tested in relation to timing of anti-TNF therapy start
      in newly diagnosed IBD patients [n = 413]: fistula formation, abscess formation,
      extra-intestinal manifestations [EIM], surgery, referral to academic centre, and
      MH. RESULTS: A total of 85 patients [21%] received anti-TNF (66 Crohn's disease
      [CD], 16 ulcerative colitis [UC], 3 inflammatory bowel disease unclassified
      [IBDU]) of whom 57% [48 patients] were treated < 16 months after diagnosis.
      Patients receiving anti-TNF early [< 16 months] did not differ from patients
      receiving anti-TNF late [> 16 months] regarding gender, age, smoking status, and
      familial IBD. More importantly, patients receiving anti-TNF early did not suffer
      less IBD-related complications during follow-up as compared with patients started
      on anti-TNF late, nor was more MH observed. Similar results were obtained when
      anti-TNF treated patient were stratified more stringently, ie < 12 months [40
      patients] vs >2 4 months [24 patients]. Cox regression analysis showed no
      beneficial correlations between anti-TNF timing and IBD-related complications.
      Anti-TNF treated patients achieving MH were 11 times less likely to develop EIMs
      compared with patients who did not achieved MH while on anti-TNF. CONCLUSIONS:
      This study was unable to confirm a benefit of earlier anti-TNF treatment on IBD
      disease complications. This could be explained by more aggressive treatment
      earlier in disease, resulting in fewer IBD complications. However, it seems more
      likely that inappropriate selection of patients for therapy leads to suboptimal
      treatment and subsequently suboptimal outcome.

PMID- 26223840
TI  - Substance P enhances microglial density in the substantia nigra through
      neurokinin-1 receptor/NADPH oxidase-mediated chemotaxis in mice.
AB  - The distribution of microglia varies greatly throughout the brain. The substantia
      nigra (SN) contains the highest density of microglia among different brain
      regions. However, the mechanism underlying this uneven distribution remains
      unclear. Substance P (SP) is a potent proinflammatory neuropeptide with high
      concentrations in the SN. We recently demonstrated that SP can regulate nigral
      microglial activity. In the present study, we further investigated the
      involvement of SP in modulating nigral microglial density in postnatal developing
      mice. Nigral microglial density was quantified in wild-type (WT) and SP-deficient
      mice from postnatal day 1 (P1) to P30. SP was detected at high levels in the SN
      as early as P1 and microglial density did not peak until around P30 in WT mice.
      SP-deficient mice (TAC1(-/-)) had a significant reduction in nigral microglial
      density. No differences in the ability of microglia to proliferate were observed
      between TAC1(-/-) and WT mice, suggesting that SP may alter microglial density
      through chemotaxic recruitment. SP was confirmed to dose-dependently attract
      microglia using a trans-well culture system. Mechanistic studies revealed that
      both the SP receptor neurokinin-1 receptor (NK1R) and the superoxide-producing
      enzyme NADPH oxidase (NOX2) were necessary for SP-mediated chemotaxis in
      microglia. Furthermore, genetic ablation and pharmacological inhibition of NK1R
      or NOX2 attenuated SP-induced microglial migration. Finally, protein kinase
      Cdelta (PKCdelta) was recognized to couple SP/NK1R-mediated NOX2 activation.
      Altogether, we found that SP partly accounts for the increased density of
      microglia in the SN through chemotaxic recruitment via a novel NK1R-NOX2 axis
      mediated pathway. 

PMID- 26223843
TI  - Multifocal Motor Neuropathy Associated with Infliximab.
AB  - BACKGROUND: The anti-tumour necrosis factor [TNF] monoclonal antibody,
      infliximab, is commonly prescribed in both ulcerative colitis and Crohn's
      disease. Neurological side effects such as optic neuritis are well recognised,
      although not as frequently seen as hypersensitivity and serious infections. CASE:
      We present a case of peripheral neuropathy in a young man on infliximab therapy
      for ulcerative colitis. This presented as an asymmetrical and slowly progressive
      weakness in his right upper limb, severely impacting on function. Investigations
      confirmed a diagnosis of multifocal motor neuropathy [MMN]. This has been
      previously described in patients receiving infliximab for rheumatological
      conditions. The exact mechanism is unclear, but the neuropathy responds well to
      intravenous immunoglobulin. In our case, infliximab was discontinued. The patient
      was treated with immunoglobin for 5 days and recovered rapidly. Mercaptopurine
      was instituted as maintanence therapy, with good effect. CONCLUSION:
      Gastroenterologists prescribing infliximab should be cognisant of both peripheral
      and central neurological complications, ensuring prompt withdrawal of the
      offending agent and appropriate alternative treatment.

PMID- 26223844
TI  - Renal Involvement in Inflammatory Bowel Diseases.
AB  - The prevalence of extraintestinal manifestations in inflammatory bowel diseases
      varies from 6% to 46%. The aetiology of extraintestinal manifestations remains
      unclear. There are theories based on an immunological response influenced by
      genetic factors. Extraintestinal manifestations can involve almost every organ
      system. They may originate from the same pathophysiological mechanism of
      intestinal disease, or as secondary complications of inflammatory bowel diseases,
      or autoimmune diseases susceptibility. The most frequently involved organs are
      the joints, skin, eyes, liver and biliary tract. Renal involvement has been
      considered as an extraintestinal manifestation and has been described in both
      Crohn's disease and ulcerative colitis. The most frequent renal involvements in
      patients with inflammatory bowel disease are nephrolithiasis, tubulointerstitial
      nephritis, glomerulonephritis and amyloidosis. The aim of this review is to
      evaluate and report the most important data in the literature on renal
      involvement in patients with inflammatory bowel disease. Bibliographical searches
      were performed of the MEDLINE electronic database from January 1998 to January
      2015 with the following key words (all fields): (inflammatory bowel disease OR
      Crohn's disease OR ulcerative colitis) AND (kidney OR renal OR nephrotoxicity OR
      renal function OR kidney disease OR renal disease OR glomerulonephritis OR
      interstitial nephritis OR amyloidosis OR kidney failure OR renal failure) AND (5
      aminosalicylic acid OR aminosalicylate OR mesalazine OR TNF-alpha inhibitors OR
      cyclosporine OR azathioprine OR drugs OR pediatric). 

PMID- 26223845
TI  - A Sensor Array Using Multi-functional Field-effect Transistors with Ultrahigh
      Sensitivity and Precision for Bio-monitoring.
AB  - Mechanically adaptive electronic skins (e-skins) emulate tactition and
      thermoception by cutaneous mechanoreceptors and thermoreceptors in human skin,
      respectively. When exposed to multiple stimuli including mechanical and thermal
      stimuli, discerning and quantifying precise sensing signals from sensors embedded
      in e-skins are critical. In addition, different detection modes for mechanical
      stimuli, rapidly adapting (RA) and slowly adapting (SA) mechanoreceptors in human
      skin are simultaneously required. Herein, we demonstrate the fabrication of a
      highly sensitive, pressure-responsive organic field-effect transistor (OFET)
      array enabling both RA- and SA- mode detection by adopting easily deformable,
      mechano-electrically coupled, microstructured ferroelectric gate dielectrics and
      an organic semiconductor channel. We also demonstrate that the OFET array can
      separate out thermal stimuli for thermoreception during quantification of SA-type
      static pressure, by decoupling the input signals of pressure and temperature.
      Specifically, we adopt piezoelectric-pyroelectric coupling of highly crystalline,
      microstructured poly(vinylidene fluoride-trifluoroethylene) gate dielectric in
      OFETs with stimuli to allow monitoring of RA- and SA-mode responses to dynamic
      and static forcing conditions, respectively. This approach enables us to apply
      the sensor array to e-skins for bio-monitoring of humans and robotics. 

PMID- 26223846
TI  - Feasibility of granular bed filtration of an aerosol of ultrafine metallic
      particles including a pressure drop regeneration system.
AB  - A process for filtering an aerosol of ultrafine metallic particles (UFP) has been
      designed and tested, based on the principle of a multistage granular bed. The
      filtration system comprised a succession of granular beds of varying thickness
      composed of glass beads of different diameters. This system allows the pressure
      drop to be regenerated during filtration ("on-line" mode) using a vibrating
      probe. Tests monitoring the pressure drop were conducted on a "10-L/min" low
      airflow rate device and on a "100-m(3)/hr" prototype. Granular bed unclogging is
      automated on the latter. The cyclic operation and filtration performances are
      similar to that of filter medium-based industrial dust collectors. IMPLICATIONS:
      Filtration of ultrafine metallic particles generated by different industrial
      processes such as arc welding, metal cutting, or spraying constitutes a difficult
      problem due to the high filter clogging properties of these particles and to the
      high temperatures generally encountered. Granular beds represent an advantageous
      means of filtering these aerosols with difficult properties.

PMID- 26223847
TI  - [Value of clinical key symptoms in the primary treatment of severely injured
      patients].
AB  - BACKGROUND: The initial diagnostic procedure of severely injured patients in the
      emergency room (ER) during the primary survey is first and foremost a clinical
      examination. The clinical S3 guidelines provide recommendations for the treatment
      of patients with severe and multiple injuries. OBJECTIVES: The study was
      performed to investigate the reliability of clinical key symptoms or red flags
      registered in the ER that lead to further diagnostic or therapeutic procedures.
      MATERIAL AND METHODS: An evaluation of key symptoms as a synopsis of the current
      literature considering aspects of probability calculation and medical experience
      was carried out. RESULTS: Key symptoms registered during the clinical examination
      are not sufficiently safe to be solely relied upon for further diagnostic and
      therapeutic decisions. This confirms the sense of purpose of the strict approach
      according to the advanced trauma life support (ATLS) algorithm. Red flags can
      serve as a warning to focus on relevant injuries early on. A rational imaging
      diagnostic procedure must follow.

PMID- 26223849
TI  - Improving the continuity of smoking cessation care delivered by quitline
      services.
AB  - OBJECTIVES: This study identified smokers' intended use of new quitline features
      aimed at improving smoking cessation such as having the same quitline advisor for
      each call, longer-term telephone counselling and provision of additional
      cessation treatments. METHODS: Smokers who had previously used quitline
      counselling completed a computer-assisted telephone interview examining intended
      use of potential quitline enhancements. RESULTS: The majority of smokers (61.1%)
      thought their chances of quitting would have increased a lot/moderately if they
      had the same quitline advisor for each call. Most smokers reported likely use of
      longer-term quitline telephone support after a failed (58.3%) or successful (60%)
      quit attempt. Smokers were likely to use quitline support long-term (mean=9.9
      months). Most smokers would be likely to use free or subsidised nicotine
      replacement therapy (NRT) (74.9%) if offered by quitlines. Younger smokers had
      greater odds of being likely to use text messages, whereas less educated smokers
      had greater odds of being likely to use free or subsidised NRT. CONCLUSIONS:
      Smokers appear interested in quitlines offering longer-term telephone support,
      increased continuity of care and additional effective quitting strategies.
      PRACTICE IMPLICATIONS: Quitlines could adopt a stepped care model that involves
      increasingly intensive treatments and extended telephone counselling delivered by
      the same quitline advisor.

PMID- 26223850
TI  - Healthcare providers' accuracy in assessing patients' pain: A systematic review.
AB  - OBJECTIVE: Healthcare providers satisfy an important role in providing
      appropriate care in the prevention and management of acute and chronic pain,
      highlighting the importance of providers' abilities to accurately assess
      patients' pain. We systematically reviewed the literature on healthcare
      providers' pain assessment accuracy. METHODS: A systematic literature search was
      conducted in PubMed and PsycINFO to identify studies addressing providers' pain
      assessment accuracy, or studies that compared patients' self-report of pain with
      providers' assessment of pain. RESULTS: 60 studies met the inclusion criteria.
      Healthcare providers had moderate to good pain assessment accuracy. Physicians
      and nurses showed similar pain assessment accuracy. Differences in pain
      assessment accuracy were found according to providers' clinical experience, the
      timing of the pain assessment, vulnerable patient populations and patients' pain
      intensity. CONCLUSION: Education and training aimed at improving providers with
      poor pain assessment accuracy is discussed especially in relation to those with
      limited clinical experience (<4 years) or a great deal of clinical experience
      (>10 years) and those providing care for vulnerable patient populations. PRACTICE
      IMPLICATIONS: More research on characteristics that influence providers' pain
      assessment accuracy and trainings to improve pain assessment accuracy in medical
      and continuing education may improve pain treatment for patients.

PMID- 26223851
TI  - Exploring the influence of patient-provider communication on intraocular pressure
      in glaucoma patients.
AB  - OBJECTIVE: We examined whether six patient-provider communication behaviors
      directly affected the intraocular pressure (IOP) of glaucoma patients or whether
      patient medication adherence and eye drop technique mediated the relationship
      between self-efficacy, communication, and IOP. METHODS: During an 8-month,
      longitudinal study of 279 glaucoma patients and 15 providers, two office visits
      were videotape-recorded, transcribed, and coded for six patient-provider
      communication behaviors. Medication adherence was measured electronically and IOP
      was extracted from medical records. We ran generalized estimating equations to
      examine the direct effects of communication on IOP and used bootstrapping to test
      whether medication adherence and eye drop technique mediated the effect of
      communication on IOP. RESULTS: Provider education about medication adherence (B=
      0.50, p<0.05) and inclusion of patient input into the treatment plan (B=-0.35,
      p<0.05) predicted improved IOP. There was no evidence of significant mediation.
      CONCLUSION: The positive effects of provider education and provider inclusion of
      patient input in the treatment plan were not mediated by adherence and eye drop
      technique. PRACTICE IMPLICATIONS: Providers should educate glaucoma patients
      about the importance of medication adherence and include patient input into their
      treatment plan.

PMID- 26223852
TI  - Success factors for BakriTM balloon usage secondary to uterine atony: a
      retrospective, multicentre study.
AB  - BACKGROUND: Post-partum haemorrhage (PPH) is one of the major obstetric
      complications and remains a cause of avoidable maternal mortality and morbidity.
      AIMS: The aims of this study were to assess the success and practicability of a
      BakriTM balloon intrauterine tamponade for PPH and evaluate the predictive
      factors for success. MATERIALS AND METHODS: Women who received the BakriTM
      balloon secondary to uterine atony and subsequent failure of routine drug
      treatment were identified at 6 hospital sites. Demographic, obstetric and
      specific factors in regard to the BakriTM balloon use were recorded. Factors
      predictive of BakriTM balloon success were evaluated. RESULTS: Intrauterine
      BakriTM balloon tamponade was used in 36 women with uterine atony of which 28
      received the balloon treatment after vaginal delivery: more than 50% of women
      (16/28) presented with PPH with blood loss > 1000 mL (mean blood loss: 1130 mL).
      Two balloon insertions failures were identified. Bakri balloon success was 100%
      for women with bleeding < 1000 mL. Twenty-five women (69%) did not require
      invasive treatment; seven (19%) required arterial embolisation and four (11%)
      surgical management. No short-term complication was observed after balloon
      insertion. CONCLUSION: The use of the BakriTM balloon method, if undertaken
      early, is effective for the management of PPH with uterine atony (100% success
      compared to 69% overall success rate). Intrauterine balloon tamponade should
      included in PPH management guidelines.

PMID- 26223853
TI  - Effects of three methane mitigation agents on parameters of kinetics of total and
      hydrogen gas production, ruminal fermentation and hydrogen balance using in vitro
      technique.
AB  - Methane (CH4 ) can be mitigated through directly inhibiting methanogen activity
      and starving methanogens by hydrogen (H2 ) sink. Three types of mechanism (i.e.
      bromoethanesulphonate (BES), nitrate and emodin) and doses of CH4 mitigation
      agents were employed to investigate their pathways of CH4 inhibition. Results
      indicated that both BES and emodin inhibited CH4 production and altered H2
      balance, which could be accompanied by decreased dry matter disappearance (DMD),
      fractional rate of gH2 formation, volatile fatty acid (VFA) production, ability
      to produce and use reducing equivalences and molecular H2 , and increased final
      asymptotic gH2 production, time to the peak of gH2 , discrete lag time of gH2
      production and fermentation efficiency. However, emodin decreased gas volume
      produced by rapidly fermentable components of substrate and the rate of
      fermentation at early stage of incubation, while BES supplementation inhibited
      gas volume produced by both rapidly and slowly fermentable components of
      substrate and the rate of fermentation at middle or late stage of incubation. The
      nitrate supplementation inhibited CH4 production without affecting VFA profile,
      because of its dual role as H2 sink and being toxic to methanogens. Nitrate
      supplementation had more complicated pattern of fermentation, VFA production and
      profile and H2 balance in comparison to BES and emodin supplementation. 

PMID- 26223854
TI  - Flow-driven assembly of VWF fibres and webs in in vitro microvessels.
AB  - Several systemic diseases, including thrombotic thrombocytopenic purpura,
      manifest much of their pathology through activation of endothelium and thrombotic
      occlusion of small blood vessels, often leading to multi-organ failure and death.
      Modelling these diseases is hampered by the complex three-dimensional
      architecture and flow patterns of the microvasculature. Here, we employ
      engineered microvessels of complex geometry to examine the pathological responses
      to endothelial activation. Our most striking finding is the capacity of
      endothelial-secreted von Willebrand factor (VWF) to assemble into thick bundles
      or complex meshes, depending on the vessel geometry and flow characteristics.
      Assembly is greatest in vessels of diameter <=300 MUm, with high shear stress or
      strong flow acceleration, and with sharp turns. VWF bundles and webs bind
      platelets, leukocytes and erythrocytes, obstructing blood flow and sometimes
      shearing passing erythrocytes. Our findings uncover the biophysical requirements
      for initiating microvascular thrombosis and suggest mechanisms for the onset and
      progression of microvascular diseases. 

PMID- 26223855
TI  - Understanding male cancer patients' barriers to participating in cancer
      rehabilitation.
AB  - The aim was to describe male cancer survivors' barriers towards participation in
      cancer rehabilitation as a means to guiding future targeted men's cancer
      rehabilitation. Symbolic Interactionism along with the interpretive descriptive
      methodology guided the study of 35 male cancer survivors representing seven
      cancer types. Data were generated through a 5-month fieldwork study comprising
      participant observations, semi-structured individual interviews and informal
      conversations. The analyses revealed two overarching findings shedding light on
      male cancer survivors' barriers to rehabilitation: 'Fear of losing control' and
      'Striving for normality'. While 'Fear of losing control' signified what the men
      believed rehabilitation would invoke: 'Reduced manliness', 'Sympathy and
      dependency' and 'Confrontation with death', 'Striving for normality' was based on
      what the men believed rehabilitation would hinder: 'Autonomy and purpose',
      'Solidarity and fellowship' and 'Forget and move on'. This study of male cancer
      survivors' and cancer rehabilitation documents how masculine ideals may
      constitute barriers for participation in rehabilitation and provides insights
      about why men are underrepresented in rehabilitation. The findings can guide
      practice to develop research-based rehabilitation approaches focused on
      preserving control and normality. Further empirical evidence is needed to: (1)
      explore the conduct of health professionals' towards male cancer patients and (2)
      address gender inequalities in cancer rehabilitation. 

PMID- 26223848
TI  - An Overview of Genome Organization and How We Got There: from FISH to Hi-C.
AB  - In humans, nearly two meters of genomic material must be folded to fit inside
      each micrometer-scale cell nucleus while remaining accessible for gene
      transcription, DNA replication, and DNA repair. This fact highlights the need for
      mechanisms governing genome organization during any activity and to maintain the
      physical organization of chromosomes at all times. Insight into the functions and
      three-dimensional structures of genomes comes mostly from the application of
      visual techniques such as fluorescence in situ hybridization (FISH) and molecular
      approaches including chromosome conformation capture (3C) technologies. Recent
      developments in both types of approaches now offer the possibility of exploring
      the folded state of an entire genome and maybe even the identification of how
      complex molecular machines govern its shape. In this review, we present key
      methodologies used to study genome organization and discuss what they reveal
      about chromosome conformation as it relates to transcription regulation across
      genomic scales in mammals. 

PMID- 26223856
TI  - Microsurgical anatomy of the trochlear nerve.
AB  - The trochlear nerve is the cranial nerve with the longest intracranial course,
      but also the thinnest. It is the only nerve that arises from the dorsal surface
      of the brainstem and decussates in the superior medullary velum. After leaving
      the dorsal surface of the brainstem, it courses anterolaterally around the
      lateral surface of the brainstem and then passes anteriorly just beneath the free
      edge of the tentorium. It passes forward to enter the cavernous sinus, traverses
      the superior orbital fissure and terminates in the superior oblique muscle in the
      orbit. Because of its small diameter and its long course, the trochlear nerve can
      easily be injured during surgical procedures. Therefore, precise knowledge of its
      surgical anatomy and its neurovascular relationships is essential for approaching
      and removing complex lesions of the orbit and the middle and posterior fossae
      safely. This review describes the microsurgical anatomy of the trochlear nerve
      and is illustrated with pictures involving the nerve and its surrounding
      connective and neurovascular structures.

PMID- 26223857
TI  - Utility of cardiac computed tomography for inflow cannula patency assessment and
      prediction of clinical outcome in patients with the HeartMate II left ventricular
      assist device.
AB  - OBJECTIVES: Proper inflow cannula orientation during implantation of the
      HeartMate II (HMII) left ventricular assist device (LVAD) is important for
      optimal pump function. This article describes our experience with cardiac
      computed tomography (CCT) to evaluate inflow cannula patency and predict future
      adverse outcomes (AE) after HMII LVAD implantation. METHODS: Ninety-three
      patients underwent HMII LVAD implantation for end-stage cardiomyopathy from
      January 2010 until March 2014. A total of 25 consecutive patients had CCT after
      the implantation; 3 patients were excluded from the analysis due to associated
      abnormality of the outflow graft. The 22 patients with CCT after HMII LVAD were
      censored for adverse events related to LVAD malfunction after HMII LVAD
      implantation. The maximum percentage of inflow cannula obstruction on CCT was
      recorded. We analysed the predictive value of CCT in addition to other clinical
      and diagnostic variables for future AEs. RESULTS: Seven of the 22 patients (32%)
      experienced AEs after HMII LVAD implantation. The degree of inflow cannula
      obstruction was higher in the group of patients who experienced an AE (70 vs 14%;
      P < 0.001). Inflow cannula obstruction >30% showed excellent correlation with AE
      longitudinally based on receiver operating curve (0.829). The group with AEs more
      frequently experienced CHF symptoms (P = 0.054). CONCLUSIONS: Inflow cannula
      obstruction >30% on CCT predicts future adverse events in patients with HMII
      LVAD; the need for surgical intervention in terms of LVAD exchange or urgent
      listing for heart transplantation should be considered in good surgical risk
      patients. Cardiac computed tomography should be considered routinely
      postoperatively in patients with HMII LVAD.

PMID- 26223858
TI  - Basing seven day working policy on evidence not political expediency.

PMID- 26223859
TI  - Decreasing transition times in elementary school classrooms: Using computer
      assisted instruction to automate intervention components.
AB  - Research suggests that students spend a substantial amount of time transitioning
      between classroom activities, which may reduce time spent academically engaged.
      This study used an ABAB design to evaluate the effects of a computer-assisted
      intervention that automated intervention components previously shown to decrease
      transition times. We examined the effects of the intervention on the latency to
      on-task behavior of 4 students in 2 classrooms. Data also were collected on
      students' on-task behavior during activities and teachers' use of prompts and
      praise statements. Implementation of the intervention substantially decreased
      students' latencies to on-task behavior and increased on-task behavior overall.
      Further, the 2 teachers used fewer prompts to cue students to transition and stay
      on task and provided more praise during intervention phases. We discuss how
      automating classroom interventions may affect student and teacher behavior as
      well as how it may increase procedural fidelity. 

PMID- 26223860
TI  - Extremely bulky secondary phosphinoamines as substituents for sterically hindered
      aminosilanes.
AB  - The synthesis of a series of extremely bulky secondary amines with a phosphine
      function, Ar(?)(PR2)NH (Ar(?) = C6H2{C(H)Ph2}2Pr(i)-2,6,4; R = Ph, NEt2, NPr(i)2)
      is described. Deprotonation with either n-BuLi or KH yields the respective alkali
      metal amides in some cases. Their reaction with the chlorosilanes SiCl4, HSiCl3,
      Cl2SiPh2, Cl3Si-SiCl3 and Si5Cl10 allows access to monomeric molecular compounds
      bearing the extremely bulky amino substituents via salt elimination. The products
      obtained may serve as precursors for subsequent reduction reactions to access
      sterically protected low valent and low coordinate silicon compounds. 

PMID- 26223861
TI  - Making patient centered care a reality: a survey of patient educational programs
      in Italian Cancer Research and Care Institutes.
AB  - BACKGROUND: Educational intervention represents an essential element of care for
      cancer patients; while several single institutions develop their own patient
      education (PE) programs on cancer, little information is available on the
      effective existence of PE programs at the level of research and care institutes.
      In Italy such institutes--Istituti di Ricovero e Cura a Carattere Scientifico-
      are appointed by the Ministry of Health, and 11 (Cancer Research & Care Istitute
      CRCI) of the 48 are specific for cancer on the basis of specific requirements
      regarding cancer care, research and education. Therefore, they represent an ideal
      and homogeneous model through which to investigate PE policies and activities
      throughout the country. The objective of this study was to assess PE activities
      in Italian CRCI. METHODS: We carried out a survey on PE strategies and services
      through a questionnaire. Four key points were investigated: a) PE as a cancer
      care priority, b) activities that are routinely part of PE, c) real involvement
      of the patients, and d) involvement of healthcare workers in PE activities.
      RESULTS: Most CRCI (85%) completed the survey. All reported having ongoing PE
      activities, and 4 of the 11 considered PE an institutional activity. More than
      90% of CRCI organize classes and prepare PE handouts, while other PE activities
      (e.g., Cancer Information Services, mutual support groups) are less frequently
      part of institutional PE programs. Patients are frequently involved in the
      organization and preparation of educational activities on the basis of their own
      needs. Various PE activities are carried out for caregivers in 8 (73%) out of 11
      institutes. Finally, health care workers have an active role in the organization
      of PE programs, although nurses take part in these activities in only half of
      CRCI and pharmacists are seldom included. CONCLUSIONS: The information arising
      from our research constitutes a necessary framework to identify areas of
      development and to design new strategies and standards to disseminate the culture
      of PE. This may ultimately help and stimulate the establishment of institutional
      integrated PE programs, including policies and interventions that can benefit a
      significant proportion of cancer patients.

PMID- 26223862
TI  - Chitosan Controls Postharvest Decay on Cherry Tomato Fruit Possibly via the
      Mitogen-Activated Protein Kinase Signaling Pathway.
AB  - The inhibitive effects of chitosan on gray mold caused by Botrytis cinerea on
      cherry tomato fruit were evaluated. Decay incidence was tested on tomato stored
      at 22  degrees C. Hydrogen peroxide accumulation, malondialdehyde (MDA)
      production, peroxidase (POD) activity, and several related gene expressions
      (including MPK3, MPK6, PR1a1, and PR5) were determined. Results showed that 0.2%
      of chitosan solution significantly inhibited the tomato gray mold 3 days after
      inoculation. Hydrogen peroxide accumulated in the fruit epidermal peel along with
      chitosan treatment, while MDA production was not increased. POD activity was
      remarkably enhanced by the application of chitosan. The relative expressions of
      MPK3, MPK6, and PR1a1 were significantly induced in 10 min after chitosan
      treatment, while PR5 was induced in 20 min. These findings suggested that the
      effects of chitosan on inhibiting gray mold in cherry tomato fruit were probably
      associated with the mitogen-activated protein kinase (MAPK) signaling pathway. 

PMID- 26223863
TI  - Mathematical Models Describing Chinese Hamster Ovary Cell Death Due to
      Electroporation In Vitro.
AB  - Electroporation is a phenomenon used in the treatment of tumors by
      electrochemotherapy, non-thermal ablation with irreversible electroporation, and
      gene therapy. When treating patients, either predefined or variable electrode
      geometry is used. Optimal pulse parameters are predetermined for predefined
      electrode geometry, while they must be calculated for each specific case for
      variable electrode geometry. The position and number of electrodes are also
      determined for each patient. It is currently assumed that above a certain
      experimentally determined value of electric field, all cells are
      permeabilized/destroyed and under it they are unaffected. In this paper,
      mathematical models of survival in which the probability of cell death is
      continuously distributed from 0 to 100 % are proposed and evaluated. Experiments
      were performed on cell suspensions using electrical parameters similar to
      standard electrochemotherapy and irreversible electroporation parameters. The
      proportion of surviving cells was determined using clonogenic assay for assessing
      the ability of a cell to grow into a colony. Various mathematical models (first
      order kinetics, Hulsheger, Peleg-Fermi, Weibull, logistic, adapted Gompertz,
      Geeraerd) were fitted to experimental data using a non-linear least-squares
      method. The fit was evaluated by calculating goodness of fit and by observing the
      trend of values of models' parameters. The most appropriate models of cell
      survival as a function of treatment time were the adapted Gompertz and the
      Geeraerd models and, as a function of the electric field, the logistic, adapted
      Gompertz and Peleg-Fermi models. The next steps to be performed are validation of
      the most appropriate models on tissues and determination of the models'
      predictive power.

PMID- 26223864
TI  - Comparison of an advanced minimally invasive cardiac output monitoring with a
      continuous invasive cardiac output monitoring during lung transplantation.
AB  - The aim of this study was to compare a continuous non-calibrated left heart
      cardiac index (CI) measurement by arterial waveform analysis
      (FloTrac((r))/Vigileo((r))) with a continuous calibrated right heart CI
      measurement by pulmonary artery thermodilution (CCOmbo-PAC((r))/Vigilance
      II((r))) for hemodynamic monitoring during lung transplantation. CI was measured
      simultaneously by both techniques in 13 consecutive lung transplants (n = 4
      single-lung transplants, n = 9 sequential double-lung transplants) at distinct
      time points perioperatively. Linear regression analysis and Bland-Altman analysis
      with percentage error calculation were used for statistical comparison of CI
      measurements by both techniques. In this study the FloTrac((r)) system
      underestimated the CI in comparison with the continuous pulmonary arterial
      thermodilution (p < 0.000). For all measurement pairs we calculated a bias of 
      0.55 l/min/m(2) with limits of agreement between -2.31 and 1.21 l/min/m(2) and a
      percentage error of 55 %. The overall correlations before clamping a branch oft
      the pulmonary artery (percentage error 41 %) and during the clamping periods of a
      branch oft the pulmonary artery (percentage error 66 %) failed to reached the
      required percentage error of less than 30 %. We found good agreement of both CI
      measurements techniques only during the measurement point "15 min after starting
      the second one-lung ventilation period" (percentage error 30 %). No agreement was
      found during all other measurement points. This pilot study shows for the first
      time that the CI of the FloTrac((r)) system is not comparable with the continuous
      pulmonary-artery thermodilution during lung transplantation including the time
      periods without clamping a branch of the pulmonary artery. Arterial waveform and
      continuous pulmonary artery thermodilution are, therefore, not interchangeable
      during these complex operations. 

PMID- 26223865
TI  - Allogeneic hematopoietic stem cell transplantation could improve survival of
      cytogenetically normal adult acute myeloid leukemia patients with DNMT3A
      mutations.
AB  - DNMT3A mutations are frequent in cytogenetically normal acute myeloid leukemia
      (cn-AML) patients and associated with poor survival. The role of allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) in DNMT3A(mut) cn-AML
      patients remains unclear. In this study, we retrospectively analyzed the
      prognostic impact of DNMT3A mutations and explored the role of allo-HSCT in 308
      cn-AML patients who received consolidation of intensive chemotherapy or allo-HSCT
      in our center from March 2005 to May 2014. In the whole cohort, 63 patients
      (20.5%) were identified with DNMT3A exon 23 mutations and R882H was the most
      frequent variant. DNMT3A(mut) patients had shorter overall survival (3-year OS:
      31.9% vs. 52.0%, P = 0.009) and disease-free survival (3-year DFS: 21.8% vs.
      40.1%, P = 0.004) compared with DNMT3A(wt) patients. Based on FLT3/NPM1/CEBPA
      mutations, 308 cn-AML patients were divided into favorable/intermediate group (n
      = 262) and unfavorable group (n = 46). There were no significant differences in 3
      year OS and 3-year DFS between DNMT3A(mut) and DNMT3A(wt) patients in both
      favorable/intermediate and unfavorable groups. Additionally, in multivariate
      analysis, DNMT3A mutation remained an independent adverse prognostic factor for
      the survival. In the DNMT3A(mut) cohort, 23 complete remission (CR) patients
      received allo-HSCT consolidation and 32 CR patients received chemotherapy
      consolidation, dramatic differences were observed in 3-year OS (51.7% vs. 28.9%,
      P = 0.048) and 3-year DFS (41.6% vs. 14.9%, P = 0.024) between allo-HSCT group
      and chemotherapy group. Collectively, DNMT3A mutation is a poor prognostic factor
      for cn-AML patients and allo-HSCT could improve survival of cn-AML patients with
      DNMT3A mutations.

PMID- 26223866
TI  - HIV, Hepatitis B and C among people who inject drugs: high prevalence of HIV and
      Hepatitis C RNA positive infections observed in Delhi, India.
AB  - BACKGROUND: India has large PWID (persons who inject drugs) population estimated
      at 177,000. PWIDs are at high risk for HIV, Hepatitis B (HBV) and Hepatitis C
      (HCV) infections. We report the prevalence of HIV, HBV and HCV infections and
      correlates of HIV-HCV co-infection among male PWIDs in Delhi. METHODS: 3748 male
      PWIDs were recruited for a longitudinal HIV incidence study. Participants were
      tested for HBV and HCV infections at their first follow-up visit (FV1) using
      serum HBV-surface antigen, and HCV-antibody tests followed by HCV RNA PCR,
      respectively. All PWIDs who were HIV-negative at enrollment, were re-tested for
      HIV at FV1. Multinomial logistic regression was employed to identify predictors
      of HIV, HCV and HIV-HCV co-infection. RESULTS: Overall prevalence of HIV, HBV and
      HCV among 2,292 participants tested at FV1 was 25.9%, 9.7% and 53.7%,
      respectively. 6.4% of the participants had HIV mono-infection, 34.1% had HCV mono
      infection, and 19.6% had HIV-HCV co-infection. 26% of HIV-positive participants
      without HCV were HBsAg positive. In the regression model, having practiced at
      least one risky injection in the past month (relative risk ratio (RRR): 1.38; 95%
      CI: 1.01-1.89) and not knowing his own HIV status (RRR: 1.65, 95% CI: 1.25-2.17)
      were independent predictors for HIV-HCV co-infection. Longer duration of drug
      injections was associated with a higher likelihood of HCV mono-infection (2-5
      years RRR: 2.13; 6-10 years RRR: 2.74; >=11 years RRR: 3.14) and HIV-HCV co
      infection (2-5 years RRR: 5.14; 6-10 years RRR: 8.53; >11 years RRR: 8.03).
      Higher frequency of injection days/month was associated with a higher likelihood
      of HCV mono-infection (<=10 days/month RRR: 1.61; 11-20 days/month RRR: 3.15; 21
      30 days/month RRR: 3.47) and HIV-HCV co-infections (<=10 days/month RRR: 2.26; 11
      20 days/month RRR: 3.46; 21-30 days/month RRR: 4.83). CONCLUSIONS: We report a
      high prevalence of HIV, HCV and HIV-HCV co-infection among male PWIDs in Delhi. A
      tenth of the participants were HBsAg positive. Targeted Intervention programs
      should make HBV/HCV testing, prevention and care more accessible for PWIDs.

PMID- 26223867
TI  - MicroRNA-106b promotes colorectal cancer cell migration and invasion by directly
      targeting DLC1.
AB  - BACKGROUND: Growing evidence suggests that microRNAs (miRNAs) play an important
      role in tumor development, progression and metastasis. Aberrant miR-106b
      expression has been reported in several cancers. However, the role and underlying
      mechanism of miR-106 in colorectal cancer (CRC) have not been addressed. METHODS:
      Quantitative RT-PCR(qRT-PCR) was performed to evaluate miR-106b levels in CRC
      cell lines and patient specimens. Cell proliferation was detected using MTT
      assay, and cell migration and invasion ability were evaluated by wound healing
      assay and transwell assay. The target gene of miR-106b was determined by qRT-PCR,
      western blot and luciferase assays. RESULTS: miR-106b was significantly up
      regulated in metastatic CRC tissues and cell lines, and high miR-106b expression
      was associated with lymph node metastasis and advanced clinical stage. In
      addition, miR-106b overexpression enhances, whereas miR-106b depletion reduces
      CRC cell migration and invasion. Moreover, we identify DLC1 as a direct target of
      miR-106b, reveal its expression to be inversely correlated with miR-106b in CRC
      samples and show that its re-introduction reverses miR-106b-induced CRC cell
      migration and invasion. Furthermore, survival analyses showed the patients with
      high mi-106b/low DLC1 had shorter overall survival (OS) and disease-free survival
      (DFS) rates, and confirmed miR-106b may be an independent prognostic factor for
      OS and DFS in CRC patients. CONCLUSIONS: Our findings indicate that miR-106b
      promotes CRC cell migration and invasion by targeting DLC1. This miRNA may serve
      as a potential prognostic biomarker and therapeutic target for CRC.

PMID- 26223868
TI  - Driver perception of brake notifications under real driving conditions.
AB  - The amount of information to be processed by drivers increases with the number of
      driver assistance systems (DAS). This implies that all relevant perception
      channels have to be used to convey information. The paper's contribution is to
      enable system designers to use differences in longitudinal acceleration as an
      information element in DAS. We conduct a study of the actual application context
      and examine the perceptible difference in longitudinal acceleration (kinaesthetic
      distortion). Thereby, we discuss dependencies of the perceptible difference on
      speed and acceleration immediately before the distortion. Furthermore, we
      investigate the spread of perceptional performance of different drivers. The
      results demonstrate smaller perceptible differences in acceleration at higher
      speed and weaker perception when the acceleration immediately before the warning
      is greater. This paper aims to provide a guideline for the implementation of
      brake warnings for informative DAS and for the adaption of the brake intensity
      according to current vehicle dynamics. PRACTITIONER SUMMARY: This paper aims to
      enable the kinaesthetic perception channel for informative driver assistance
      systems. A real world driving study reveals the perceptible difference in
      longitudinal acceleration (kinaesthetic distortion) depending on vehicle speed
      and acceleration and serves as a guideline for applying brake warnings as an
      information element in vehicles.

PMID- 26223869
TI  - A functional variant in the UBE2B gene promoter is associated with idiopathic
      azoospermia.
AB  - BACKGROUND: A variety of genetic variants lead to abnormal human spermatogenesis.
      The ubiquitin-conjugating enzyme E2B (UBE2B) plays a significant role in
      spermatogenesis as Ube2b-knockout male mice are infertile. METHODS: In this
      study, we sequenced the exon and promoter region of UBE2B in 776 patients
      diagnosed with idiopathic azoospermia (IA) and 709 proven fertile men to examine
      whether UBE2B is involved in the pathogenesis of IA. RESULTS: In the exon region,
      two novel synonymous variants were detected in the patient group. In the promoter
      region, four known variants and four novel variants were identified in the
      patient group. Of the novel variants in the promoter region, three were located
      at the binding site of specificity protein 1 (SP1) transcription factor analyzed
      by TRANSFAC software. Luciferase assays demonstrated that one heterozygous
      variant (Chr5.133706925 A > G) inhibited the transcriptional regulation activity
      of SP1. CONCLUSIONS: A novel variant (Chr5.133706925 A > G) residing in the UBE2B
      gene promoter region confers a high risk for IA in a Chinese population. These
      results support a role for UBE2B in the pathogenesis of IA.

PMID- 26223870
TI  - Efficacy of weekly docetaxel in locally advanced cardiac angiosarcoma.
AB  - BACKGROUND: Primary cardiac angiosarcoma is extremely aggressive; however, it is
      often misdiagnosed because of its rarity. For locally advanced tumors,
      doxorubicin-based chemotherapy regimens are the standard of treatment, even if
      the gain in term of progression-free survival is limited and is no longer than 5
      months. CASE PRESENTATION: We report the case of a Caucasian 23-year-old man with
      locally advanced cardiac angiosarcoma who underwent radical surgical resection
      after a prolonged response to weekly docetaxel and complementary radiotherapy.
      CONCLUSION: Combined treatment with weekly docetaxel and radiotherapy may be a
      valid alternative for the treatment of locally advanced cardiac angiosarcoma; the
      combination can lead to radical surgical resections, avoiding the cumulative
      cardiotoxicity of antracycline-based regimens.

PMID- 26223871
TI  - The bacterial colonization in tunneled cuffed dialysis catheter and its effects
      on residual renal function in incident hemodialysis patients.
AB  - BACKGROUND: The bacterial colonization of hemodialysis catheter occurs frequently
      and reaches to the catheter-related bloodstream infections (CRBSIs). We
      hypothesized bacterial colonization promotes inflammation and that might be
      associated with renal outcome. The aim of this study was to investigate the
      colonization status for tunneled cuffed dialysis catheter (TCC) and the factors
      for contributing to the catheter colonization and explore whether bacterial
      colonization would be related with declining of residual renal function (RRF).
      METHODS: 115 patients who received TCC removal operation and underwent catheter
      tip culture from January 2005 to June 2014 were enrolled. The follow-up data such
      as urine output (UO), time to anuria and patients' survival were collected from
      the patients or their family members by telephone in June, 2014. RESULTS: There
      were nineteen patients (16.5 %, 19/115) with positive tip culture (colonization
      group). In the analysis of demographic and biochemical parameters, there were no
      significant differences between both groups. Fifty of all the subjects responded
      to the telephone survey and ten patients (20.0 %, 10/50) belonged to colonization
      group. The monthly decreasing rate of UO was significantly more rapid in
      colonization group (p = 0.001). The survival analysis showed that colonization
      group had worse estimated anuria-free survival than non-colonization group (p <
      0.001). In multivariate cox regression, bacterial colonization of TCC was an
      independent factor influencing the loss of RRF (HR 4.29, 95 % CI: 1.905-9.683, p
      <= 0.001). CONCLUSIONS: Bacterial colonization of TCC was associated with rapid
      loss of RRF.

PMID- 26223872
TI  - Current Concepts in Management of Pulmonary Hypertension: Fighting the Old Demon
      with Modern Weapons.
AB  - Pulmonary hypertension in children is a rare disease associated with high
      morbidity and mortality. The pathogenesis is not fully understood. Diagnostic
      evaluation focuses on ruling out other etiologies of pulmonary hypertension and
      prognosticating the disease. Congenital heart disease and left sided heart
      disease associated pulmonary hypertension are more common in children. Therapies
      for idiopathic pulmonary hypertension have evolved over the past decade.
      Phosphodiesterase 5 inhibitors (sildenafil, tadalafil), endothelin antagonists
      (Bosentan and ambrisentan) and prostanoids are the classes of drugs shown to be
      useful in pulmonary hypertension. However, use of these drugs in children is
      based on extrapolation of adult usage and on expert consensus rather than based
      on randomized controlled trial evidence. Despite these advances, the outcomes of
      various forms of pulmonary hypertension remain poor, especially in India, where
      some forms of therapy are not available and children often are diagnosed at an
      advanced stage of disease.

PMID- 26223873
TI  - Correlation of Bone Mineral Parameters with Anthropometric Measurements and the
      Effect of Glucocorticoids on Bone Mineral Parameters in Congenital Adrenal
      Hyperplasia.
AB  - OBJECTIVE: To correlate the bone mineral parameters [bone mineral content (BMC)
      and bone mineral density (BMD)] using Dual energy X ray Absorptiometry (DXA) scan
      with anthropometric measurements and to study the effect of glucocorticoid
      therapy on BMC/BMD in children with Congenital adrenal hyperplasia (CAH).
      METHODS: A cross-sectional study was carried out in the Pediatric Endocrinology
      unit from January 2012 through March 2013 at Kanchi Kamakoti CHILDS Trust
      hospital, Chennai. Thirteen CAH children aged 0-132 mo with classic salt wasting
      due to 21 hydroxylase deficiency were included in the study. All children were
      treated with T.hydrocortisone @10-15 mg/m(2)/d twice daily and T. fludrocortisone
      50 MUg once daily orally at the time of enrollment into the study. The duration
      of glucocorticoid (hydrocortisone) treatment from the date of diagnosis till the
      time of enrollment into the study was noted and categorized as children receiving
      < 5 and > 5 y of glucocorticoid therapy. None received Vitamin D/calcium
      supplementation at the time of enrollment. BMC and areal BMD for the lumbar spine
      and total body less head (TBLH) were measured with Lunar DXA machine. RESULTS:
      The mean height, weight and BMI of children were 87.3 +/- 33 cm, 13.49 +/- 11.2
      kg and 14 +/- 4.07 kg/m(2) respectively. TBLH BMC was 369.14 +/- 312.18 g and
      TBLH BMD was 0.63 +/- 0.11 g/cm(2). There was a significant correlation between
      height and total body less head BMC/BMD in the index series [P < 0.05,
      significant]. The TBLH and spine BMD were also assessed with regards to the
      duration of glucocorticoid therapy and it has been observed that TBLH and spine
      BMD decreased with increased duration of steroid therapy (p < 0.05, significant).
      CONCLUSIONS: In the absence of normative data or z scores, BMC/BMD correlates
      well with height for age. Children who received more than 5 y of glucocorticoid
      treatment had lower TBLH and spine BMD scores and hence, calcium and Vitamin D
      supplementation should be considered.

PMID- 26223874
TI  - Home Mechanical Ventilation in Children.
AB  - The number of children dependent on home mechanical ventilation has been reported
      to be increasing in many countries around the world. Home mechanical ventilation
      has been well accepted as a standard treatment of children with chronic
      respiratory failure. Some children may need mechanical ventilation as a lifelong
      therapy. To send mechanically ventilated children back home may be more difficult
      than adults. However, relatively better outcomes have been demonstrated in
      children. Children could be safely ventilated at home if they are selected and
      managed properly. Conditions requiring home ventilation include increased
      respiratory load from airway or lung pathologies, ventilatory muscle weakness and
      failure of neurologic control of ventilation. Home mechanical ventilation should
      be considered when the patient develops progressive respiratory failure or
      intractable failure to wean mechanical ventilation. Polysomnography or overnight
      pulse oximetry plus capnometry are used to detect nocturnal hypoventilation in
      early stage of respiratory failure. Ventilator strategy including non-invasive
      and invasive approach should be individualized for each patient. The author
      strongly believes that parents and family members are able to take care of their
      child at home if they are trained and educated effectively. A good team work with
      dedicated members is the key factor of success. 

PMID- 26223875
TI  - Superselective Angiographic Embolization for Arteriovenous Fistula after a
      Protocol Biopsy in a Kidney Transplanted Child.

PMID- 26223876
TI  - An immunohistochemical analysis of SERT in the blood-brain barrier of the male
      rat brain.
AB  - 5-Hydroxytryptamine (5-HT) was originally discovered as a vasoconstrictor. 5-HT
      lowers blood pressure when administered peripherally to both normotensive and
      hypertensive male rats. Because the serotonin transporter (SERT) can function
      bidirectionally, we must consider whether 5-HT can be transported from the
      bloodstream to the central nervous system (CNS) in facilitating the fall in blood
      pressure. The blood-brain barrier (BBB) is a highly selective barrier that
      restricts movement of substances from the bloodstream to the CNS and vice versa,
      but the rat BBB has not been investigated in terms of SERT expression. This
      requires us to determine whether the BBB of the rat, the species in which we
      first observed a fall in blood pressure to infused 5-HT, expresses SERT. We
      hypothesized that SERT is present in the BBB of the male rat. To test this
      hypothesis, over 500 blood vessels were sampled from coronal slices of six male
      rat brains. Immunofluorescence of these coronal slices was used to determine
      whether SERT and RecA-1 (an endothelial cell marker) colocalized to the BBB.
      Blood vessels were considered to be capillaries if they were between 1.5 and 23
      um (intraluminal diameter). SERT was identified in the largest pial vessels of
      the BBB (mean +/- SEM = 228.70 +/- 18.71 um, N = 9) and the smallest capillaries
      (mean +/- SEM = 2.75 +/- 0.12 um, N = 369). SERT was not identified in the
      endothelium of blood vessels ranging from 20 to 135 um (N = 45). The expression
      of SERT in the rat BBB means that 5-HT entry into the CNS must be considered a
      potential mechanism when investigating 5-HT-induced fall in blood pressure. 

PMID- 26223877
TI  - Transepithelial electrical resistance (TEER): a functional parameter to monitor
      the quality of oviduct epithelial cells cultured on filter supports.
AB  - Cultivation of oviduct epithelial cells on porous filters fosters in vivo-like
      morphology and functionality. However, due to the optical properties of the
      filter materials and the cells' columnar shape, cell quality is hard to assess
      via light microscopy. In this study, we aim to evaluate transepithelial
      electrical resistance (TEER) measurement as a prognostic quality indicator for
      the cultivation of porcine oviduct epithelial cells (POEC). POEC were maintained
      in four different types of media for 3 and 6 w to achieve diverse culture
      qualities, and TEER was measured before processing samples for histology. Culture
      quality was scored using morphological criteria (presence of cilia, confluence
      and cell polarity). We furthermore analyzed the correlation between cellular
      height (as a measure of apical-basal polarization) and TEER in fully
      differentiated routine cultures (biological variation) and in cultures with
      altered cellular height due to hormonal stimulation. Fully differentiated
      cultures possessed a moderate TEER between 500 and 1100 Omega*cm(2). Only 5% of
      cultures which exhibited TEER values in this defined range had poor quality. Sub
      differentiated cultures showed either very low or excessively high TEER. We
      unveiled a highly significant (P < 0.0001) negative linear correlation between
      TEER and epithelial height in well-differentiated cultures (both routine and
      hormone stimulated group). This may point toward the interaction between tight
      junction assembly and epithelial apical-basal polarization. In conclusion, TEER
      is a straightforward quality indicator which could be routinely used to monitor
      the differentiation status of oviduct epithelial cells in vitro.

PMID- 26223878
TI  - The unpredictable consequences of CDKN1B/p27Kip1 mutations in cancer.

PMID- 26223879
TI  - Effect of low-pressure plasma treatment on the color and oxidative stability of
      raw pork during refrigerated storage.
AB  - The effect of low-pressure plasma on quality attributes of meat is an important
      aspect, which must be considered before application in food. The aim of this
      study was to determine the color, fatty acid composition, lipid oxidation
      expressed as thiobarbituric acid reactive substances and total antioxidant
      capacity of raw pork samples exposed to helium low-pressure plasma treatment (20
      kPa) for 0, 2, 5, and 10 min during the storage period. The thiobarbituric acid
      reactive substance concentrations of all plasma-treated samples during storage
      were in the range from 0.26 to 0.61 mg malondialdehyde/kg. Exposure time caused
      significant changes only in total color difference, hue angle, and chroma after
      10 min of treatment. Ferric reducing ability of plasma values of meat samples
      decreased from 1.93 to 1.40 mmol Trolox Eq/kg after 14 days of storage. The
      storage period significantly affected proportion of polyunsaturated fatty acids,
      with an increase about 3% after 14 days of refrigeration storage while the
      content of saturated fatty acids was at the same level. Helium low-pressure
      plasma does not induce oxidative processes. Application of this decontamination
      technique while maintaining product quality is possible in food industry. 

PMID- 26223880
TI  - Publishing and sharing multi-dimensional image data with OMERO.
AB  - Imaging data are used in the life and biomedical sciences to measure the
      molecular and structural composition and dynamics of cells, tissues, and
      organisms. Datasets range in size from megabytes to terabytes and usually contain
      a combination of binary pixel data and metadata that describe the acquisition
      process and any derived results. The OMERO image data management platform allows
      users to securely share image datasets according to specific permissions levels:
      data can be held privately, shared with a set of colleagues, or made available
      via a public URL. Users control access by assigning data to specific Groups with
      defined membership and access rights. OMERO's Permission system supports simple
      data sharing in a lab, collaborative data analysis, and even teaching
      environments. OMERO software is open source and released by the OME Consortium at
      www.openmicroscopy.org.

PMID- 26223881
TI  - Orthology for comparative genomics in the mouse genome database.
AB  - The mouse genome database (MGD) is the model organism database component of the
      mouse genome informatics system at The Jackson Laboratory. MGD is the
      international data resource for the laboratory mouse and facilitates the use of
      mice in the study of human health and disease. Since its beginnings, MGD has
      included comparative genomics data with a particular focus on human-mouse
      orthology, an essential component of the use of mouse as a model organism. Over
      the past 25 years, novel algorithms and addition of orthologs from other model
      organisms have enriched comparative genomics in MGD data, extending the use of
      orthology data to support the laboratory mouse as a model of human biology. Here,
      we describe current comparative data in MGD and review the history and refinement
      of orthology representation in this resource. 

PMID- 26223882
TI  - Site-specific activity of the acyltransferases HtrB1 and HtrB2 in Pseudomonas
      aeruginosa lipid A biosynthesis.
AB  - Pseudomonas aeruginosa (PA) is an opportunistic Gram-negative pathogen associated
      with nosocomial infections, acute infections and chronic lung infections in
      patients with cystic fibrosis. The ability of PA to cause infection can be
      attributed to its ability to adapt to a multitude of environments. Modification
      of the lipid A portion of lipopolysaccharide (LPS) is a vital mechanism Gram
      negative pathogens use to remodel the outer membrane in response to environmental
      stimuli. Lipid A, the endotoxic moiety of LPS, is the major component of the
      outer leaflet of the outer membrane of Gram-negative bacteria making it a
      critical factor for bacterial adaptation. One way PA modifies its lipid A is
      through the addition of laurate and 2-hydroxylaurate. This secondary or late
      acylation is carried out by the acyltransferase, HtrB (LpxL). Analysis of the PA
      genome revealed the presence of two htrB homologs, PA0011 (htrB1) and PA3242
      (htrB2). In this study, we were able to show that each gene identified is
      responsible for site-specific modification of lipid A. Additionally, deletions of
      either gene altered resistance to specific classes of antibiotics, cationic
      antimicrobial peptides and increased membrane permeability suggesting a role for
      these enzymes in maintaining optimal membrane organization and integrity. 

PMID- 26223883
TI  - Hemagglutinin gene shuffling among Clostridium botulinum serotypes C and D yields
      distinct sugar recognition of the botulinum toxin complex.
AB  - Clostridium botulinum strains produce a large-sized toxin complex (TC) that is
      composed of botulinum neurotoxin (BoNT), non-toxic non-hemagglutinin and three
      different hemagglutinins (HA-70, HA-33 and HA-17). HA components enhance toxin
      delivery across the intestinal cell wall in a sugar chain-dependent manner. Here
      we characterized the sugar recognition of serotype D strain 1873 (D-1873)
      botulinum L-TC. Most L-TCs produced by serotype C and D strains bind to cells via
      interactions between HA-33 and cell surface sialo-oligosaccharides. However, like
      the previously reported L-TC produced by serotype C strain Yoichi (C-Yoichi), D
      1873 L-TC binds only to cells that have been treated with neuraminidase,
      indicating that they recognize asialo-oligosaccharides. The D-1873 HA-33 amino
      acid sequence is similar to that of C-Yoichi, but had lower similarity to the
      majority of serotype C and D HA-33s. A comparison of TC component primary
      structures for 12 serotype C and D strains suggested that at least three types of
      HA-33 genes exist, and these are shuffled among the serotype C and D strains
      independently of BoNT serotype. This shuffling produces the distinct sugar
      recognition of serotype C and D botulinum TCs. 

PMID- 26223884
TI  - Prognostic molecular markers in resected extrahepatic biliary tract cancers; a
      systematic review and meta-analysis of immunohistochemically detected biomarkers.
AB  - Better prognostic information for resected extrahepatic cholangiocarcinoma could
      guide treatment strategies and potentially improve outcome. This study performed
      a systematic review and meta-analysis to identify prognostic biomarkers for
      further investigation. METHODS: Relevant literature was identified using Medline,
      EMBASE and Web of Science. Primary end point was overall survival assessed on
      univariate analysis. Log hazard ratio and variance were calculated and pooled
      using a random effects inverse variance approach. Hazard ratio and 95% confidence
      intervals were calculated. RESULTS: Thirty-seven studies, including 2371
      patients, met the inclusion criteria. Subsequently nine biomarkers predictive of
      OS were identified (HR, 95% CI): VEGF (2.32, 1.57-3.44), COX-2 (1.94, 1.01-3.71),
      GLUT-1 (2.09, 1.52-2.89), Cyclin D1 (1.96, 1.02-3.76), p16 (0.68, 0.47-0.98), p27
      (0.48, 0.3-0.78), E-Cadherin (0.47, 0.35-0.63), Fascin (2.19, 1.35-3.55), and Ki
      67 (1.69, 1.02-2.79). CONCLUSION: Meta-analysis has identified a number of
      prognostic biomarkers for resected extrahepatic cholangiocarcinoma. These markers
      warrant further investigation as potential therapeutic targets and validation in
      a prospective setting.

PMID- 26223885
TI  - QSPR study on refractive indices of solvents commonly used in polymer chemistry
      using flexible molecular descriptors.
AB  - A predictive Quantitative Structure-Property Relationship (QSPR) for the
      refractive indices of 370 solvents commonly used in the processing and analysis
      of polymers is presented, using as chemical information descriptors the
      simplified molecular input line entry system (SMILES). The model employs a
      flexible molecular descriptor and a conformation-independent approach. Various
      well-known techniques, such as the use of an external test set of compounds, the
      cross-validation method, and Y-randomization were used to test and validate the
      established equations. The predicted values were finally compared with published
      results from the literature. The simple model proposed correlates the refractive
      index values with good accuracy, and it is not dependent on 3D-molecular
      geometries. 

PMID- 26223886
TI  - Association of malocclusion, happiness, and oral health-related quality of life
      (OHRQoL) in schoolchildren.
AB  - OBJECTIVE: The aim of this study was to assess the impact of malocclusion on
      children's oral health-related quality of life (COHRQoL) and self-reported
      happiness. METHODS: A cross-sectional study was conducted in a representative
      sample of 12-year-old schoolchildren from Santa Maria, South Brazil. Four
      calibrated examiners carried out clinical exams to evaluate malocclusion [Dental
      Aesthetic Index (DAI)], dental caries (DMFT), and dental trauma (O'Brien
      classification, used in the Children's dental health survey in the UK, 1994).
      Participants answered the Brazilian versions of the Child Perceptions
      Questionnaire (CPQ11-14 ) and the Subjective Happiness Scale (SHS). Parents
      completed a structured questionnaire regarding socioeconomic status. Data
      analysis was conducted using multilevel Poisson regression models. RESULTS: A
      total of 1,134 adolescents (boys: 45.8 percent; girls: 54.1 percent) were
      enrolled in the study. The DAI overall score ranged from 13 to 63 (mean: 25.19,
      standard error: 0.19); 57.6 percent of the subjects had minor or no malocclusion
      and 24.4 percent had definite malocclusion. Severe malocclusion and handicapping
      malocclusion were found in 10.4 percent and 7.4 percent of the subjects,
      respectively. After adjustment, the severity of malocclusion was associated with
      high mean values of the CPQ11-14 overall score, and the emotional well-being and
      social well-being domains were the most affected. Lower levels of happiness were
      also associated with the severity of malocclusion: those with definite
      malocclusion presented lower scores on the SHS scale (Rate Ratio 0.97; 95 percent
      CI 0.94-0.99). CONCLUSION: Malocclusion had a negative impact on COHRQoL and
      happiness, mainly on the emotional and social domains.

PMID- 26223887
TI  - Medium-chain acyl-CoA dehydrogenase deficiency associated with a novel splice
      mutation in the ACADM gene missed by newborn screening.
AB  - BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most
      common disorder of mitochondrial fatty acid beta-oxidation and a target disease
      of newborn screening in many countries. CASE PRESENTATION: We report on two
      siblings with mild MCAD deficiency associated with a novel splice site mutation
      in the ACADM gene. The younger sibling was detected by newborn screening, while
      the older sister was missed, but diagnosed later on by genetic family testing.
      Both children were found to be compound heterozygous for the common c.985A > G
      (p.K329E) mutation and a novel splice site mutation, c.600-18G > A, in the ACADM
      gene. To determine the biological consequence of the c.600-18G > A mutation
      putative missplicing was investigated at RNA level in granulocytes and monocytes
      of one of the patients. The splice site mutation was shown to lead to partial
      missplicing of the ACADM pre-mRNA. Of three detected transcripts two result in
      truncated, non-functional MCAD proteins as reflected by the reduced octanoyl-CoA
      oxidation rate in both patients. In one patient a decrease of the octanoyl-CoA
      oxidation rate was found during a febrile infection indicating that missplicing
      may be temperature-sensitive. CONCLUSIONS: Our data indicate that the c.600-18G >
      A variant activates a cryptic splice site, which competes with the natural splice
      site. Due to only partial missplicing sufficient functional MCAD protein remains
      to result in mild MCADD that may be missed by newborn screening.

PMID- 26223888
TI  - The assumption of radon-induced cancer risk.

PMID- 26223889
TI  - Urinary melatonin and risk of ovarian cancer.
AB  - PURPOSE: Melatonin has anti-carcinogenic properties, including modulation of
      estradiol production, cell cycle regulation, and promotion of apoptosis. Urinary
      melatonin has been inversely associated with breast cancer in some studies, but
      the association with ovarian cancer has not been investigated. METHODS: We
      measured urinary 6-sulfatoxymelatonin (aMT6s) in nested ovarian cancer case
      control studies in the Nurses' Health Study (NHS; n = 100 cases; 199 controls)
      and NHSII (n = 52 cases; 105 controls); samples were mainly from first morning
      voids. Controls were matched to cases on year of birth, menopause status, use of
      menopausal hormone therapy, and urine collection characteristics. We evaluated
      the association of tertiles of aMT6s, corrected for creatinine concentrations,
      with risk of ovarian cancer using conditional logistic regression. Models were
      adjusted for key ovarian cancer risk factors, and we additionally evaluated
      adjustment for usual sleep duration, snoring, and history of rotating night shift
      work. RESULTS: aMT6s was not significantly associated with risk of ovarian
      cancer. In multivariable models, the odds ratio comparing the highest tertile of
      aMT6s to the lowest was 0.79, 95 % confidence interval (CI) 0.40-1.56 in the NHS
      and 2.88, and 95 % CI in the NHSII 0.97-8.52. Additional adjustment for sleep
      habits and night shift work had little impact on the observed results. We
      observed no clear association between urinary melatonin and ovarian cancer risk.
      CONCLUSIONS: These results are consistent with our previous study in which we
      reported no association between night shift work and ovarian cancer; however,
      given the small sample size in our study, additional evaluation in larger studies
      is warranted.

PMID- 26223890
TI  - Persistence of Trichomonas vaginalis serostatus in men over time.
AB  - PURPOSE: Previous epidemiologic studies have observed positive associations
      between Trichomonas vaginalis (Tv) serostatus and both prostate cancer (PCa) risk
      and mortality. However, only a few small older studies have examined Tv antibody
      persistence over time, all of which were composed mainly of female patients.
      Therefore, we examined Tv antibody persistence over time, as well as intra
      individual variability, among middle- to older-aged men in the Southern Community
      Cohort Study (SCCS). METHODS: We tested baseline and repeat plasma specimens
      (collected 1-3 years later) from 248 male participants for Tv antibodies. We used
      the same enzyme-linked immunosorbent assay as in previous studies of Tv
      serostatus and PCa. RESULTS: At baseline, 46 (18.5 %) participants were
      seropositive for Tv infection. Seventy-six percent of these men were still
      seropositive 1-3 years later. A similar proportion of men "seroconverted" (4.0 %)
      as "seroreverted" (4.4 %), all of whom had absorbance values near the cutoff
      point for seropositivity. Overall, substantial agreement was observed between
      baseline and repeat serostatus (kappa = 0.72, 95 % confidence interval 0.60
      0.83). CONCLUSION: Tv seropositivity was largely persistent between plasma
      specimens collected 1-3 years apart from middle- to older-aged men. These high
      levels of persistence are similar to those observed for other sexually
      transmitted infections frequently investigated in relation to PCa.

PMID- 26223891
TI  - FGF21 protects against ox-LDL induced apoptosis through suppressing CHOP
      expression in THP1 macrophage derived foam cells.
AB  - BACKGROUND: FGF21,as a member of the fibroblast growth factor superfamily, is an
      important endogenous regulator to systemic glucose and lipid metabolism. Elevated
      serum FGF21 levels have been reported in subjects with coronary heart disease and
      carotid artery plaques. The formation and apoptosis of foam cell, induced by ox
      LDL and oxysterols, are key steps in the development of atherosclerosis. METHODS:
      In this study, THP1 derived macrophages were induced into foam cells by ox-LDL or
      sterols. The formation and apoptosis of foam cells treated with or without FGF21
      were analyzed. RESULTS: We demonstrated that the accumulation of cholesterol was
      decreased after FGF21 treatment in THP1 macrophage derived foam cells.
      Consistently, the apoptosis of macrophage was alleviated dramatically with FGF21
      treatment. ERK1/2 knockdown didn't abrogate the effect of FGF21 on THP1
      macrophage derived foam cells. However, FGF21 suppressed the induced expression
      of CHOP and DR5 in THP1 macrophage derived foam cells. CONCLUSION: FGF21 protects
      against the formation and apoptosis of THP1 macrophages derived foam cells
      through suppressing the expression of CHOP.

PMID- 26223892
TI  - Population-specific plasma proteomes of marine and freshwater three-spined
      sticklebacks (Gasterosteus aculeatus).
AB  - Molecular phenotypes that distinguish resident marine (Bodega Harbor) from
      landlocked freshwater (FW, Lake Solano) three-spined sticklebacks were revealed
      by label-free quantitative proteomics. Secreted plasma proteins involved in lipid
      transport, blood coagulation, proteolysis, plasminogen-activating cascades,
      extracellular stimulus responses, and immunity are most abundant in this species.
      Globulins and albumins are much less abundant than in mammalian plasma. Unbiased
      quantitative proteome profiling identified 45 highly population-specific plasma
      proteins. Population-specific abundance differences were validated by targeted
      proteomics based on data-independent acquisition. Gene ontology enrichment
      analyses and known functions of population-specific plasma proteins indicate
      enrichment of processes controlling cell adhesion, tissue remodeling, proteolytic
      processing, and defense signaling in marine sticklebacks. Moreover, fetuin B and
      leukocyte cell derived chemotaxin 2 are much more abundant in marine fish. These
      proteins promote bone morphogenesis and likely contribute to population-specific
      body armor differences. Plasma proteins enriched in FW fish promote translation,
      heme biosynthesis, and lipid transport, suggesting a greater presence of plasma
      microparticles. Many prominent population-specific plasma proteins (e.g.
      apoptosis-associated speck-like protein containing a CARD) lack any homolog of
      known function or adequate functional characterization. Their functional
      characterization and the identification of population-specific environmental
      contexts and selective pressures that cause plasma proteome diversification are
      future directions emerging from this study. 

PMID- 26223893
TI  - The predictive role of infiltrative growth pattern in early pharyngeal cancers.
AB  - CONCLUSION: The infiltrative growth pattern may predict tumor depth and lymph
      node metastasis. INF-a seems to fall into a low-risk category, and no additional
      treatment may be required immediately. OBJECTIVES: Tumor depth is a predictor of
      lymph node metastasis in early pharyngeal cancers. An infiltrative growth pattern
      is also a prognostic factor in other cancers. This study aimed to elucidate the
      predictive role of infiltrative growth pattern in early pharyngeal cancers.
      METHODS: Thirty-eight lesions from 37 patients who had undergone trans-oral
      resection of pharyngeal cancers were included. According to the Japanese
      Classification of Esophageal Cancer, infiltrative growth pattern was classified
      into three groups; INF-a, INF-b, and INF-c. The correlation between infiltrative
      growth pattern and tumor depth, cervical lymph node metastasis was analyzed.
      RESULTS: Of the 38 lesions, 25 were INF-a, nine were INF-b, and four were INF-c
      lesions. Lymph node metastasis was observed in three INF-b and one INF-c lesions.
      In contrast, no INF-a had lymph node metastasis. All INF-a lesions showed shallow
      invasion of the sub-epithelium; INF-b and INF-c lesions had significantly greater
      depth than INF-a.

PMID- 26223894
TI  - ADHD across the lifespan-IMpACT on genetics of adult ADHD.

PMID- 26223895
TI  - The Medical Cost Attributable to Obesity and Overweight in China: Estimation
      Based on Longitudinal Surveys.
AB  - With its rapid economic growth and fast changing lifestyle, China witnessed
      expansionary prevalence of obesity and overweight during the recent decades. This
      paper provides the first nationally representative estimate of the medical cost
      attributable to obesity and overweight in China. We improve upon the traditional
      estimation methodology (two-part model) by jointly adopting the instrumental
      variable approach and the panel data methods in order to correct for the
      potential endogeneity of body size and the individual heterogeneity in medical
      expenditure. Using longitudinal data from 2000-2009 China Health and Nutrition
      Surveys, we find that body size has a significant impact on the individual
      expected medical expenditure and the per capita medical cost attributable to
      obesity and overweight in a single medical event is estimated to be 6.18 Yuan, or
      5.29% of the total personal medical expenditure. This translates to 24.35 billion
      Yuan annual cost on the national scale, accounting for 2.46% of China's national
      health care expenditure. The subsample analyses also show that such cost is
      higher for the urban, women, and better educated people and increases over time.
      Our results contribute to the literature on the economic impact of obesity in
      developing countries and bear policy implications on controlling the rising
      health care costs in China. Copyright (c) 2015 John Wiley & Sons, Ltd.

PMID- 26223896
TI  - Rapid Column-Free Enrichment of Mononuclear Cells from Solid Tissues.
AB  - We have developed a rapid negative selection method to enrich rare mononuclear
      cells from human tissues. Unwanted and antibody-tethered cells are selectively
      depleted during a Ficoll separation step, and there is no need for magnetic-based
      reagents and equipment. The new method is fast, customizable, inexpensive,
      remarkably efficient, and easy to perform, and per sample the overall cost is
      less than one-tenth the cost associated with a magnetic column-based method. 

PMID- 26223897
TI  - Dietary Advanced Glycation End Products Consumption as a Direct Modulator of
      Insulin Sensitivity in Overweight Humans: A Study Protocol for a Double-Blind,
      Randomized, Two Period Cross-Over Trial.
AB  - BACKGROUND: Advanced glycation end products (AGEs) are formed during the
      processing, storage, and cooking of foods. As part of a western diet, AGEs are
      consumed in excess and impair glucose metabolism in patients with type 2
      diabetes. In the absence of diabetes, AGE-mediated decreases in insulin
      sensitivity and signaling have been postulated. However, randomized studies to
      test this relationship in humans are limited. OBJECTIVE: The primary aim of this
      trial is to determine whether dietary consumption of AGEs will decrease insulin
      sensitivity in healthy overweight adults. A secondary aim is to determine the
      effects of dietary AGEs on insulin secretion, circulating soluble receptor for
      AGEs (sRAGE), and inflammation markers. METHODS: Overweight, but otherwise
      healthy, non-diabetic adults (N=20) aged 18-50 years old will complete a
      randomized cross-over design intervention study alternating low and high (4-fold
      increase) AGE diets (2-week duration). At baseline, participants will undergo a
      medical review including an intravenous glucose tolerance test (IVGTT), a
      hyperinsulinemic-euglycemic clamp, and anthropometric measures and questionnaires
      assessing diet, physical activity, and general wellness. Each test diet will be
      followed for 14 days, followed by a 4-week washout period before commencement of
      the second alternate dietary period. Energy, macronutrient, and AGE intake will
      be calculated for each dietary period. Additionally, the AGE content of foods
      used in the study will be measured by ultra performance liquid chromatography
      mass spectrometry. All measurements will be repeated at the beginning and end of
      each dietary period. Primary and secondary outcomes will be expressed as a change
      over the dietary period for insulin sensitivity, secretion, anthropometric
      parameters, sRAGE, and inflammation markers and compared by paired t test and
      analysis of variance (ANOVA). RESULTS: The study will be completed in early 2016.
      CONCLUSION: The proposed trial will provide much needed clinical evidence on the
      impact of excess dietary AGE consumption on insulin sensitivity and will indicate
      whether lowering dietary AGE intake can improve insulin sensitivity and/or
      secretion, thereby decreasing risk for type 2 diabetes. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT00422253; https://clinicaltrials.gov/ct2/show/NCT00422253
      (Archived by Webcite at http://www.webcitation.org/6ZXLhT89c).

PMID- 26223898
TI  - An Investigation of Organizational and Regulatory Discourses of Workplace
      Bullying.
AB  - Organizations use policies to set standards for employee behaviors. Although many
      organizations have policies that address workplace bullying, previous studies
      have found that these policies affect neither workplace bullying for targets who
      are seeking assistance in ending the behaviors nor managers who must address
      incidents of bullying. This article presents the findings of a study that used
      critical discourse analysis to examine the language used in policies written by
      health care organizations and regulatory agencies to regulate workplace bullying.
      The findings suggest that the discussion of workplace bullying overlaps with
      discussions of disruptive behaviors and harassment. This lack of conceptual
      clarity can create difficulty for managers in identifying, naming, and
      disciplining incidents of workplace bullying. The documents also primarily
      discussed workplace bullying as a patient safety concern. This language is in
      conflict with organizations attending to worker well-being with regard to
      workplace bullying. 

PMID- 26223899
TI  - An Overview of Metformin and Implications in the Workplace.
AB  - Diabetes mellitus is expensive; one of the top 10 most costly health concerns for
      employers. Individuals with type 2 diabetes mellitus (T2DM) who achieve glycemic
      targets through healthy lifestyles and appropriate glucose-lowering agents lessen
      diabetes-related complications. The purpose of this article is to provide a brief
      review of a first-line agent used in treating T2DM, the biguanide metformin
      hydrochloride. Implications for health providers who assist employees who use
      metformin also are addressed. 

PMID- 26223900
TI  - Risk factors for service use and trends in coverage of different HIV testing and
      counselling models in northwest Tanzania between 2003 and 2010.
AB  - OBJECTIVES: To investigate the relative effectiveness of different HIV testing
      and counselling (HTC) services in improving HIV diagnosis rates and increasing
      HTC coverage in African settings. METHODS: Patient records from three HTC
      services [community outreach HTC during cohort study rounds (CO-HTC), walk-in HTC
      at the local health centre (WI-HTC) and antenatal HIV testing (ANC-HTC)] were
      linked to records from a community cohort study using a probabilistic record
      linkage algorithm. Characteristics of linked users of each HTC service were
      compared to those of cohort participants who did not use the HTC service using
      logistic regression. Data from three cohort study rounds between 2003 and 2010
      were used to assess trends in the proportion of persons testing at different
      service types. RESULTS: The adjusted odds ratios for HTC use among men with
      increasing numbers of sexual partners in the past year, and among HIV-positive
      men and women compared to HIV-negative men and women, were higher at WI-HTC than
      at CO-HTC and ANC-HTC. Among sero-survey participants, the largest numbers of HIV
      positive men and women learned their status via CO-HTC. However, we are likely to
      have underestimated the numbers diagnosed at WI-HTC and ANC-HTC, due to low
      sensitivity of the probabilistic record linkage algorithm. CONCLUSIONS: Compared
      to CO-HTC or ANC-HTC, WI-HTC was most likely to attract HIV-positive men and
      women, and to attract men with greater numbers of sexual partners. Further
      research should aim to optimise probabilistic record linkage techniques, and to
      investigate which types of HTC services most effectively link HIV-positive people
      to treatment services relative to the total cost per diagnosis made.

PMID- 26223901
TI  - Global emergency medicine: a review of the literature from 2014.
AB  - OBJECTIVES: The Global Emergency Medicine Literature Review (GEMLR) conducts an
      annual search of peer-reviewed and gray literature relevant to global emergency
      medicine (EM) to identify, review, and disseminate the most important new
      research in this field to a worldwide audience of academics and clinical
      practitioners. METHODS: This year 6,376 articles written in six languages were
      identified by our search. These articles were distributed among 20 reviewers for
      initial screening based on their relevance to the field of global EM. An
      additional two reviewers searched the gray literature. A total of 477 articles
      were deemed appropriate by at least one reviewer and approved by the editor for
      formal scoring of overall quality and importance. RESULTS: Of the 477 articles
      that met our predetermined inclusion criteria, 63% were categorized as emergency
      care in resource-limited settings, 13% as EM development, and 23% as disaster and
      humanitarian response. Twenty-five articles received scores of 17.5 or higher and
      were selected for formal summary and critique. Inter-rater reliability for two
      reviewers using our scoring system was good, with an intraclass correlation
      coefficient of 0.657 (95% confidence interval = 0.589 to 0.713). Studies and
      reviews focusing on infectious diseases, trauma, and the diagnosis and treatment
      of diseases common in resource-limited settings represented the majority of
      articles selected for final review. CONCLUSIONS: In 2014, there were fewer total
      articles, but a slightly higher absolute number of articles screening in for
      formal scoring, when compared to the 2013 review. The number of EM development
      articles decreased, while the number of disaster and humanitarian response
      articles increased. As in prior years, the majority of articles focused on
      infectious diseases and trauma.

PMID- 26223902
TI  - Carcinoid heart disease: a remarkable recovery.
AB  - A 65-year-old female patient with metastatic neuroendocrine tumour of the small
      intestine developed carcinoid valve disease and intractable right heart failure.
      She underwent successful cardiac valve replacement of both tricuspid and
      pulmonary valves. One year after surgery, she has regained full functional
      capacity. 

PMID- 26223904
TI  - Carnosic acid protects normal mouse hepatocytes against H2 O2 -induced
      cytotoxicity via sirtuin 1-mediated signaling.
AB  - AIM: Carnosic acid (CA) is well known for its antioxidant properties. The aim of
      this study was to examine the effects of CA on cytotoxicity under oxidative
      stress. METHODS: Primary hepatocytes and AML12 cells were treated with: (i) 0.1
      MUM, 1 MUM and 10 MUM CA; (ii) 3 mM H2 O2 with or without 1 MUM CA; or (iii) 3 mM
      H2 O2 with 1 MUM CA and 0.04 MUM sirtuin 1 (SIRT1) inhibitor EX527 or 10 MUM
      mitogen-activated protein kinase (MAPK) inhibitor U0126. Cell viability,
      intracellular reactive oxygen species (ROS) and lactate dehydrogenase (LDH)
      leakage were determined. In addition, total protein levels of cleaved caspase 3,
      SIRT1, phosphorylated Nrf2, 5'-adenosine monophosphate-activated protein kinase
      (AMPK) and MAPKs were evaluated by western blot analysis and suspension array
      system. RESULTS: First, although 10 MUM CA produced cytotoxicity, CA at
      concentrations at or below 1 MUM did not inhibit cell viability. Second, H2 O2
      increased total cellular ROS and LDH leakage and decreased cell viability,
      whereas co-treatment with H2 O2 and 1 MUM CA significantly inhibited these
      effects of H2 O2 . Third, CA at 1 MUM increased protein levels of SIRT1.
      Pretreatment with EX527 or transfection of siRNA-targeting SIRT1 weakened the
      protective effects of CA against H2 O2 -induced cell death. Fourth, H2 O2 induced
      phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in
      primary hepatocytes. U0126 inhibited oxidative damage induced by H2 O2 . Co
      treatment with CA inhibited ERK1/2 activation induced by H2 O2 . CONCLUSION: Our
      data indicate that CA protects against oxidative stress-induced cytotoxicity via
      SIRT1 by regulating subsequent downstream factors such as ERK1/2.

PMID- 26223903
TI  - Muscle-Bone Crosstalk in Amyotrophic Lateral Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS), also called Lou Gehrig's disease, is a fatal
      neuromuscular disorder characterized by degeneration of motor neurons and by
      skeletal muscle atrophy. Although the death of motor neurons is a pathological
      hallmark of ALS, the potential role of other organs in disease progression
      remains to be elucidated. Skeletal muscle and bone are the two largest organs in
      the human body. They are responsible not only for locomotion but also for
      maintaining whole body normal metabolism and homeostasis. Patients with ALS
      display severe muscle atrophy, which may reflect intrinsic defects in
      mitochondrial respiratory function and calcium (Ca) signaling in muscle fibers,
      in addition to the role of axonal withdrawal associated with ALS progression.
      Incidence of fractures is high in ALS patients, indicating there are potential
      bone defects in individuals with this condition. There is a lifelong interaction
      between skeletal muscle and bone. The severe muscle degeneration that occurs
      during ALS progression may potentially have a significant impact on bone
      function, and the defective bone may also contribute significantly to
      neuromuscular degeneration in the course of the disease. Due to the nature of the
      rapid and severe neuromuscular symptoms, a majority of studies on ALS have
      focused on neurodegeneration. Just a few studies have explored the possible
      contribution of muscle defects, even fewer on bone defects, and fewer still on
      possible muscle-bone crosstalk in ALS. This review article discusses current
      studies on bone defects and potential defects in muscle-bone crosstalk in ALS.

PMID- 26223905
TI  - Activation Effect of Fullerene C60 on the Carbon Dioxide Absorption Performance
      of Amine-Rich Polypropylenimine Dendrimers.
AB  - Converting amine-rich compounds into highly effective carbon dioxide (CO2 )
      sorbents requires a better understanding and control of their properties. The
      reaction of fullerene C60 with polyethyleneimine converts the polymer into a high
      performance CO2 sorbent. In this study, experimental evidence is reported for the
      activation effect of C60 on the amine moieties of the polymer. To do so,
      polypropylenimine (PPI) dendrimers that allowed for a systematic comparison of
      molecular composition and CO2 absorption were used. The addition of C60 to PPI to
      form PPI-C60 results in a reduction of the energy barrier of CO2 absorption, but
      also in a parallel decrease in the frequency of successful collisions between CO2
      and PPI-C60 due to a possible disruption of the hydrogen-bonding network of amino
      groups and bound water in PPI. This finding supports the existence of a non
      affinity "repulsive" effect between hydrophobic C60 and hydrophilic amines that
      forces them to be actively exposed to CO2.

PMID- 26223906
TI  - Amphiphilic triblocks to control assembly of mixed or segregated bilayers and
      monolayers.
AB  - Triblock amphiphilic molecules composed of three distinct segments provide a
      large parameter space to obtain self-assembled structures beyond what is
      achievable with conventional amphiphiles. To obtain a molecular understanding of
      the thermodynamics of self-assembly, we develop a coarse-grained triblock polymer
      model and apply self-consistent field theory to investigate the packing mechanism
      into layer structures. By tuning the structural and interaction asymmetry, we are
      able to obtain bilayers and monolayers, where the latter may additionally be
      mixed (symmetric) or segregated (asymmetric). Of particular interest for a
      variety of applications are the asymmetric monolayers, where segregation of end
      blocks to opposite surfaces is expected to have important implications for the
      development of functional nanotubes and vesicles with distinct surface
      chemistries. 

PMID- 26223908
TI  - Base-Promoted/Gold-Catalyzed Intramolecular Highly Selective and Controllable
      Detosylative Cyclization.
AB  - A highly selective, controllable and synthetically useful base-promoted
      intramolecular detosylative cyclization of bis-N-tosylhydrazones has been
      achieved, affording N-containing heterocycles and cyclic olefins under transition
      metal-free or gold-catalyzed procedures, respectively. Moreover, an effective and
      practical metal-free or gold-catalyzed approach to synthesize polycyclic aromatic
      compounds is also reported. 

PMID- 26223907
TI  - Feasibility of Genome-Wide Screening for Biosafety Assessment of Probiotics: A
      Case Study of Lactobacillus helveticus MTCC 5463.
AB  - Recent years have witnessed an explosion in genome sequencing of probiotic
      strains for accurate identification and characterization. Regulatory bodies are
      emphasizing on the need for performing phase I safety studies for probiotics. The
      main hypothesis of this study was to explore the feasibility of using genome
      databases for safety screening of strains. In this study, we attempted to develop
      a framework for the safety assessment of a potential probiotic strain,
      Lactobacillus helveticus MTCC 5463 based on genome mining for genes associated
      with antibiotic resistance, production of harmful metabolites, and virulence. The
      sequencing of MTCC 5463 was performed using GS-FLX Titanium reagents. Genes
      coding for antibiotic resistance and virulence were identified using Antibiotic
      Resistance Genes Database and Virulence Factors Database. Results indicated that
      MTCC 5463 carried antibiotic resistance genes associated with beta-lactam and
      fluoroquinolone. There is no threat of transfer of these genes to host gut
      commensals because the genes are not plasmid encoded. The presence of genes for
      adhesion, biofilm, surface proteins, and stress-related proteins provides
      robustness to the strain. The presence of hemolysin gene in the genome revealed a
      theoretical risk of virulence. The results of in silico analysis complemented the
      in vitro studies and human clinical trials, confirming the safety of the
      probiotic strain. We propose that the safety assessment of probiotic strains
      administered live at high doses using a genome-wide screening could be an
      effective and time-saving tool for identifying prognostic biomarkers of
      biosafety. 

PMID- 26223909
TI  - Enigmatic entity in childhood: clival chordoma from a tertiary center's
      perspective.
AB  - PURPOSE: Chordoma is a rare neoplasm that arises from embryonic notochordal
      remnants along the axial skeleton (i.e., clivus, sacrum) and the vertebral
      bodies. They comprise less than 1 % of CNS tumors and 1-4 % of all bone
      malignancies. It rarely affects children and adolescents (<5 %). Chordomas are
      locally aggressive and highly recurrent. Their management is challenging for
      clinicians. METHODS: This retrospective study includes six pediatric patients
      with pathological evidence of clival chordoma. These cases were identified over a
      period of 15 years in a tertiary care institute. RESULTS: There were two boy and
      four girls with a mean age of 10.6 years (range, 4-16 years). The chief complaint
      was due to cranial nerve palsy (or dysfunction), mostly affecting lower cranial
      nerves (66.6 %), followed by diplopia and headache. One patient had obstructive
      sleep apnea. All patients were operated and a total of 15 surgeries were
      performed (mean, 2.5). Tumor recurrence was observed in four patients (67 %). Two
      year and 5-year progression-free survivals (PFS) were 67 and 33 %, respectively.
      None of the patients were lost either during the surgery or the follow-up period
      (6.9 years: 1-14 years). CONCLUSIONS: Clival chordomas are challenging tumors in
      neurosurgical practice. A multidisciplinary approach is warranted in each
      patient. Today, the best management strategy seems to be surgical resection
      followed by radiotherapy. Chemotherapy should be considered in selective and
      preference basis. Sharing institutional experiences will provide future insights
      in prognosis of these rare tumors. Implementing newer surgical instruments,
      endoscope in particular, is encouraged in management of the clival chordomas.

PMID- 26223910
TI  - Cerebellar and bone metastasis from primary cardiac sarcoma: an unusual case.

PMID- 26223911
TI  - Deep brain stimulation as treatment for dystonic storm in pantothenate kinase
      associated neurodegeneration syndrome: case report of a patient with homozygous
      C.628 2 T > G mutation of the PANK2 gene.
AB  - Pantothenate kinase-associated neurodegeneration (PKAN) syndrome is an autosomal
      recessive neurodegenerative disease that causes progressive generalized dystonia.
      Currently, the disorder remains pharmacologically intractable. Herein we report
      the first case in which deep brain stimulation helped to relieve dystonic storm
      in a patient with PKAN syndrome who had homozygous c.628 2 T > G mutation of the
      PANK2 gene. A 10-year-old boy with PKAN disease presented with dystonic storm and
      was admitted to the emergency department. Examination revealed generalized
      dystonia and impaired breathing due to involvement of the respiratory muscles.
      The patient underwent surgery for bilateral globus pallidus internus deep brain
      stimulation. The patient showed marked response to treatment.

PMID- 26223912
TI  - Binding of human SWI1 ARID domain to DNA without sequence specificity: A
      molecular dynamics study.
AB  - SWI1 is a member of a new class of tumor DNA-binding proteins named as the AT
      rich interaction domain family (ARID), and considered to bind with AT base pairs
      specifically. Genomic and functional data support ARID1A as a tumor suppressor
      because ARID1A/BAF250a (SWI1) subunit of the SWI/SNF chromatin-remodeling complex
      has emerged as recurrently mutated in a broad array of tumor types. But the
      crystal structure of SWI1 has not been solved as yet. Using docking and molecular
      dynamics, we predicted the DNA interaction pattern of human SWI1 ARID and made
      comparisons with the other two representative ARID family members, human Mrf-2
      ARID and Drosophila Dri ARID. Dynamic results revealed that the N-terminal and
      loop L1 of SWI1 ARID bound with the DNA major groove, while the loop L2 and helix
      H6 bound with the minor groove. Moreover, it was found that SWI1 ARID bound with
      DNA apparently in a sequence-nonspecific manner. It was concluded that SWI1 ARID
      can form stable complex with sequence-nonspecific DNA segment comparing to Mrf-2
      ARID/DNA and Dri ARID/DNA sequence-specific complexes. 

PMID- 26223913
TI  - Umbilical cord blood-derived mesenchymal stem cells ameliorate graft-versus-host
      disease following allogeneic hematopoietic stem cell transplantation through
      multiple immunoregulations.
AB  - Although mesenchymal stem cells (MSCs) are increasingly used to treat graft
      versus-host disease (GVHD), their immune regulatory mechanism in the process is
      elusive. The present study aimed to investigate the curative effect of third
      party umbilical cord blood-derived human MSCs (UCB-hMSCs) on GVHD patients after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their immune
      regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were
      treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK cells,
      Treg cells and dendritic cells (DCs) and cytokines including interleukin-17 (IL
      17) and tumor necrosis factor-alpha (TNF-alpha) were monitored before and after
      MSCs transfusion. The results showed that the symptoms of GVHD were alleviated
      significantly without increased relapse of primary disease and transplant-related
      complications after MSCs transfusion. The number of CD3(+), CD3(+)CD4(+) and
      CD3(+)CD8(+) cells decreased significantly, and that of NK cells remained
      unchanged, whereas the number of CD4(+) and CD8(+) Tregs increased and reached a
      peak at 4 weeks; the number of mature DCs, and the levels of TNF-alpha and IL-17
      decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate
      GVHD and spare GVL effect via immunoregulations.

PMID- 26223914
TI  - Resveratrol-downregulated phosphorylated liver kinase B1 is involved in
      senescence of acute myeloid leukemia stem cells.
AB  - Senescence is an important obstacle to cancer development. Engaging a senescent
      response may be an effective way to cure acute myeloid leukemia (AML). The aim of
      this study was to examine the effect of resveratrol-downregulated phosphorylated
      liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem
      cells. The protein expressions of pLKB1 and Sirtuin 1 (SIRT1), a regulator of
      pLKB1, were measured in CD34(+)CD38(-) KG1a cells treated with resveratrol (40
      MUmol/L) or not by Western blotting. Senescence-related factors were examined,
      including p21 mRNA tested by real-time PCR, cell morphology by senescence
      associated beta-galactosidase (SA-beta-gal) staining, cell proliferation by MTT
      assay and cell cycle by flow cytometry. Besides, apoptosis was flow
      cytometrically determined. The results showed that pLKB1 was highly expressed in
      CD34(+)CD38(-) KG1a cells, and resveratrol, which could downregulate pLKB1
      through activation of SIRT1, induced senescence and apoptosis of CD34(+)CD38(-)
      KG1a cells. It was concluded that resveratrol-downregulated pLKB1 is involved in
      the senescence of AML stem cells. 

PMID- 26223915
TI  - Effect of high-fat diet on cholesterol metabolism in rats and its association
      with Na+/K+-ATPase/Src/pERK signaling pathway.
AB  - Abnormal cholesterol metabolism is associated with an elevated risk of developing
      atherosclerosis, hypertension, and diabetes etc. Na(+)/K(+)-ATPase was found to
      regulate cholesterol synthesis, distribution and trafficking. This study aimed to
      examine the effect of high-fat diet on cholesterol metabolism in rats and the
      role of Na(+)/K(+)-ATPase/Src/ERK signaling pathway in the process. Forty male SD
      rats were evenly divided into high-fat diet group and control group at random.
      Animals in the former group were fed on high-fat diet for 12 weeks, and those fed
      on basic diet served as control. Blood lipids, including total cholesterol (TC),
      triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density
      lipoprotein-cholesteral (LDL-C) levels, were detected at 3, 6 and 12 weeks. The
      ratio of cholesterol content in cytoplasm to that in cell membrane was detected
      in liver tissues. RT-PCR and Western blotting were used to measure the expression
      of lipid metabolism-associated genes (HMG-CoA reductase and SREBP-2) after 12
      week high-fat diet. Na(+)/K(+)-ATPase/Src/ERK signaling pathway-related
      components (Na(+)/K(+)-ATPase alpha1, Src-PY418 and pERK1/2) were also measured
      by Western blotting. The results showed that the serum TC, TG, and LDL-C levels
      were significantly higher in high-fat diet group than those in control group,
      while the HDL-C level was significantly lower in high-fat diet group at 6 weeks
      (P<0.01). High-fat diet led to an increase in the cholesterol content in the
      cytoplasm and cell membrane. The ratio of cholesterol content in cytoplasm to
      that in cell membrane was elevated over time. The expression of HMG-CoA reductase
      and SREBP-2 was significantly suppressed at mRNA and protein levels after 12-week
      high-fat diet (P<0.05). Moreover, high-fat diet promoted the expression of
      Na(+)/K(+)-ATPase alpha1 but suppressed the phosphorylation of Src-PY418 and
      ERK1/2 at 12 weeks (P<0.05). It was concluded that high-fat diet regulates
      cholesterol metabolism, and Na(+)/K(+)-ATPase signaling pathway is involved in
      the process possibly by regulating the expression of lipid metabolism-associated
      proteins HMG-CoA reductase and SREBP-2. 

PMID- 26223916
TI  - Regulatory effects of AT1R-TRAF6-MAPKs signaling on proliferation of intermittent
      hypoxia-induced human umbilical vein endothelial cells.
AB  - Endothelial dysfunction induced by intermittent hypoxia (IH) participates in
      obstructive sleep apnea syndrome (OSAS)-associated cardiovascular disorders.
      Myeloid differentiation primary response 88 (MyD88) and tumor necrosis factor
      receptor-associated factor 6 (TRAF6) regulate numerous downstream adaptors like
      mitogen-activated protein kinases (MAPKs) and the subsequent oxidative stress and
      inflammatory responses. This study aimed to characterize the role of MyD88/TRAF6
      in IH-treated cell function and its associated signaling. Human umbilical vein
      endothelial cells (HUVECs) were randomly exposed to IH or normoxia for 0, 2, 4
      and 6 h. Western blotting was used to detect the expression pattern of target
      gene proteins [angiotensin 1 receptor (AT1R), p-ERK1/2, p-p38MAPK, MyD88 and
      TRAF6], and the relationships among these target genes down-regulated by the
      corresponding inhibitors were studied. Finally, the influence of these target
      genes on proliferation of HUVECs was also assessed by EdU analysis. Protein
      levels of AT1R, TRAF6 and p-ERK1/2 were increased after IH exposure, with a
      slight rise in MyD88 and a dynamic change in p-p38MAPK. The down-regulation of
      TRAF6 by siRNA reduced ERK1/2 phosphorylation during IH without any effects on
      AT1R. Blockade of AT1R with valsartan decreased TRAF6 and p-ERK1/2 protein
      expression after IH exposure. ERK1/2 inhibition with PD98059 suppressed only AT1R
      expression. IH promoted HUVECs proliferation, which was significantly suppressed
      by the inhibition of TRAF6, AT1R and ERK1/2. The findings demonstrate that TRAF6
      regulates the proliferation of HUVECs exposed to short-term IH by modulating cell
      signaling involving ERK1/2 downstream of AT1R. Targeting the AT1R-TRAF6-p-ERK1/2
      signaling pathway might be helpful in restoring endothelial function.

PMID- 26223917
TI  - Single nucleotide polymorphism of CYP3A4 intron 2 and its influence on CYP3A4
      mRNA expression and liver enzymatic activity in human liver.
AB  - In adult liver, CYP3A4 plays an important role in the metabolism of a wide range
      of endogenous and exogenous compounds. To investigate whether there is a single
      nucleotide polymorphism (SNP) of CYP3A4 intron 2 in the liver and its effects on
      the mRNA expression and enzymatic activity of CYP3A4, genomic DNA was extracted
      from 96 liver tissue samples obtained from patients who had undergone liver
      surgery. An SNP of CYP3A4 intron 2 was identified by polymerase chain reaction
      (PCR)-single-strand confirmation polymorphism and DNA sequencing. The mRNA
      expression of CYP3A4 was determined by the fluorescence quantitative PCR
      technique. The enzymatic activity of CYP3A4 was measured using erythromycin and
      testosterone as probe substrates. Twelve patients were found to have the
      SNP/T4127G CYP3A4 within intron 2. The mRNA levels of CYP3A4 in wild-type and
      SNP/T4127G samples were 2.62+/-1.09 and 2.79+/-1.63, respectively (P>0.05).
      Erythromycin N-demethylase activity in wild-type and SNP/T4127G samples were
      121.2+/-32.8 and 124.7+/-61.6 nmol.mg(-1).min(-1), respectively (P>0.05). The
      activity of testosterone 6beta-hydroxylase was significantly different between
      wild-type (648+/-173 pmol.mg(-1).min(-1)) and SNP/T4127G samples (540+/-196
      pmol.mg(-1).min(-1); P<0.05). In conclusion, the SNP/T4127G of CYP3A4 intron 2
      exists in the liver. This SNP does not affect the mRNA expression of CYP3A4 but
      significantly decreases the hepatic microsomal testosterone 6beta-hydroxylase
      activity of CYP3A4. Furthermore, this study indicates that the appropriate
      selection of probe substrates is very important in studying the relationship
      between the genotype and phenotype of CYP3A4.

PMID- 26223918
TI  - Effects of lanthanum carbonate on vascular calcification in elderly maintenance
      hemodialysis patients.
AB  - The effect of lanthanum carbonate on abdominal aortic calcification (AAC) in the
      elderly maintenance hemodialysis (MHD) patients was investigated. Fifty-four
      cases subjected to routine MHD complicated with skin pruritus admitted to our
      hospital were selected and randomly divided into case group (n=28) and control
      group (n=26). The control group was given routine MHD alone. The case group was
      given lanthanum carbonate additionally on the basis of routine MHD. The changes
      of itching degrees at first and third month, and serum calcium, phosphorus,
      calcium-phosphorus products, intact parathyroid hormone (iPTH) levels and AAC
      scores at third month after treatments were compared between the two groups. The
      correlation between calcium-phosphorus products and AAC scores was also analyzed.
      There was no significant difference in the baseline of blood urea nitrogen (BUN),
      serum creatinine (Scr), uric acid, albumin, hemoglobin, C reactive protein (CRP),
      low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride,
      total cholesterol between case group and control group (P>0.05 for all). There
      was also no significant difference in the baseline itching scores between the
      case group and the control group (P>0.05). At 1st and 3rd month after treatment,
      the itching scores in the case group were 14.2 +/- 3.2 and 10.5 +/- 2.3,
      respectively, which were significantly lower than the baseline and those in the
      control group (P<0.05 for all). At 1st and 3rd month after treatment, the itching
      scores in the control group were 23.6 +/- 5.9 and 24.8 +/- 6.3, respectively,
      which were significantly higher than the baseline (P<0.05). There was no
      significant difference in the baseline of serum calcium, phosphorus, calcium
      phosphorus products, iPTH levels between the case group and control group
      (P>0.05). At 3rd month after treatment, serum phosphorus, calcium-phosphorus
      products and iPTH levels in the case group were decreased significantly as
      compared with the baseline (P<0.05), and the serum calcium, phosphorus, calcium
      phosphorus products, and iPTH levels were statistically decreased as compared
      with those in the control group (P<0.05). The AAC scores showed statistically
      significant difference between the case group and the control group (P<0.05). The
      serum phosphorus and AAC scores showed a positive correlation in both two groups.
      It was suggested that the administration of lanthanum carbonate in the elderly
      MHD patients can effectively relieve itching, and simultaneously reduce serum
      phosphorus and iPTH levels, resulting in the attenuation of vascular
      calcification.

PMID- 26223919
TI  - Neuroprotective effect of escitalopram oxalate in rats with chronic
      hypoperfusion.
AB  - The neuroprotective effects of escitalopram oxalate in rats with chronic
      hypoperfusion and the possible mechanism were explored. Chronic hypoperfusion (2
      VO) model was prepared and given escitalopram oxalate (experimental group) or PBS
      (control group) after 6 weeks. Eight weeks after the operation, Morris water maze
      test was carried out to evaluate the learning and memory ability of the rats. The
      cell proliferation, three-dimensional vascular distribution, cell morphological
      changes in ischemic area and the plasma vascular endothelial growth factor (VEGF)
      were detected to explore the possible mechanisms. (1) Morris water maze test
      showed that the escape latency in the experimental group was significantly
      shorter than in the control group, while the first quadrant swimming time in the
      experimental group was significantly longer than the control group (both P<0.01).
      (2) Cerebrovascular confocal detection results showed that the inside diameter of
      capillaries was significantly less in the experimental group than in the control
      group; the vascular density was significantly increased in the experimental group
      and the total area of capillaries was also significantly increased in the
      experimental group as compared with the control group. (3) There was
      statistically significant difference in BrdU-positive cells in the ischemic brain
      tissue between the experimental group and the control group (P=0.003<0.01). (4)
      VEGF concentrations in the plasma and the ischemic area were higher in the
      experimental group than in the control group (P<0.05). It was concluded that
      escitalopram oxalate could significantly improve the learning and memory ability
      of the rats with chronic cerebral ischemia probably by the VEGF-mediated
      angiogenesis. 

PMID- 26223920
TI  - Effects of Yinchenhao decoction on self-regulation of renin-angiotensin system by
      targeting angiotensin converting enzyme 2 in bile duct-ligated rat liver.
AB  - In order to investigate whether Yinchenhao decoction (YCHD) attenuates hepatic
      fibrogenesis in the bile duct ligation (BDL) model via recovering and restoring
      the self-regulation and balance of the renin-angiotensin system (RAS), 33
      specific-pathogen-free (SPF) male Sprague-Dawley rats with common BDL and
      scission were randomly divided into five groups as follows: G1, the sham group
      (n=4); G2, BDL 7-day group (n=5); G3, BDL+YCHD 430 mg/mL (n=8); G4, BDL+losartan
      0.65 mg/mL (ARB group, n=8); G5, model group (BDL without any treatment, n=8).
      YCHD and losartan (10 mL.kg(-1).day(-1)) were given by gastric gavage for 16 days
      following BDL in G3 and G4 groups, respectively. The effect of YCHD on liver
      fibrosis and the detailed molecular mechanisms were assessed by liver function
      including total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin
      (IDBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST).
      Histological changes were observed by transmission electron microscopy (TEM) and
      Masson trichrome staining. Western blotting was used to detect the protein
      expression level of the renin-angiotensin system (RAS) components including
      angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), ACE2,
      angiotensin II (AngII) as well as transforming growth factor beta1 (TGFbeta1).
      The experimental data were analyzed by principle component analytical method of
      pattern recognition. The results showed that biochemically, serum TBIL, DBIL,
      IDBIL, ALT and AST levels were markedly increased following BDL as compared with
      the sham group (P<0.05). Serum TBIL, IDBIL and DBIL levels in G3 group were
      dramatically decreased as compared with G5 and G4 groups (P<0.05). Serum AST
      level in G3 was significantly lowered than in G5 group (P<0.05), but there was no
      significant difference in ALT among G3, G4 and G5 groups (P>0.05).
      Histologically, livers in G3 group showed less hepatocytes necrosis, less bile
      duct hyperplasia and less collagen formation than in G4 and G5 groups. The
      protein expression levels of ACE2, ACE, AngII, AT1R and TGFbeta1 in G2, G3 and G4
      groups were significantly higher than in sham group (P<0.05), and lower than in
      G5 group (P<0.05). However, the differences among G2, G3 and G4 groups were not
      significant (P>0.05). ACE2 protein expression in G3 group was significantly
      higher than in G2 group (P<0.05) and there was no significant difference in
      comparison with G4 group (P>0.05). Moreover, the protein expression of TGFbeta1
      in G3 group was significantly lower than in G5 and G4 groups (P<0.05). Our
      findings suggest that the antifibrotic effects of YCHD may be associated with the
      decreased classical RAS pathway components and TGFbeta1 downexpression so as to
      recover and rebuild self-regulation of the RAS by elevating the protein
      expression of ACE2.

PMID- 26223921
TI  - Effect of Qing'e formula on circulating sclerostin levels in patients with
      postmenopausal osteoporosis.
AB  - Serum sclerostin is positively associated with serum 25 hydroxyvitamin D
      concentration. Our preliminary studies confirmed that Qing'e formula (QEF) could
      effectively increase serum 25 hydroxyvitamin D concentration in patients with
      postmenopausal osteoporosis (PMOP), but the effect of supplementation with QEF on
      serum sclerostin is unknown. This study investigated the effects of
      supplementation of QEF on serum sclerostin levels in patients with PMOP. Totally
      120 outpatients and inpatients with PMOP treated in our hospital between January
      and October 2012 were randomly divided into QEF+calcium group,
      alfacalcidol+calcium group, and placebo+calcium group (n=40 each), with a follow
      up period of 2 years. The serum levels of sclerostin, 25 hydroxyvitamin D, and
      bone turnover markers (beta-CTX, N-MID and T-PINP) at baseline and at the 6th
      month, 1st year, 1.5th year, and 2nd year after treatment were measured. The
      results showed that the levels of circulating sclerostin were increased
      significantly at the 6th month after treatment in QEF+calcium group and
      alfacalcidol+calcium group as compared with placebo+calcium group (P<0.05), but
      there was no significant difference between the former two groups (P>0.05). The
      levels of beta-CTX, N-MID and T-PINP in serum were decreased in both QEF+calcium
      group and alfacalcidol+calcium group at the 6th month after treatment, without
      significant difference between the two groups (P>0.05). But the levels were
      significantly lower than that in placebo+calcium group (P<0.05). These results
      suggest that the mechanism by which QEF modulates bone metabolism in patients
      with PMOP might be related with the effect of QEF in increasing sclerostin
      expression. Our findings provide a scientific rationale for using QEF as an
      effective drug to prevent bone loss in PMOP. 

PMID- 26223922
TI  - Effect of Pin1 inhibitor juglone on proliferation, migration and angiogenic
      ability of breast cancer cell line MCF7Adr.
AB  - This study aimed to evaluate the effects of Pin1 inhibitor Juglone on
      proliferation, migration and the angiogenic ability of breast cancer cell line
      MCF7Adr. MCF7Adr cells were cultured and separately treated with Pin1 inhibitor
      Juglone (treatment group) and DMEM without drug (control group). The cell cycle
      was examined by flow cytometry. Cell migration was measured by wound-healing
      assay. Cyclin E protein content was detected by Western blotting. The
      angiogenesis factor vascular endothelial growth factor (VEGF) in cell media was
      determined by enzyme linked immunosorbent assay. The results showed that the
      percentage of cells in G2/M phase in treatment group was significantly higher
      than that in control group (25.5% vs. 10.1%, P<0.05), and that in G0/G1 phase and
      S stage in treatment group was significantly lower than that in control group
      (40.5% vs. 48.2%, and 33.7% vs. 41.7%, P<0.05). Cyclin E protein content in
      treatment group was significantly lower than that in control group (39.2 +/- 7.4
      vs. 100 +/- 23.1, P<0.05). (A0-A24)/A0 value in treatment group was significantly
      lower than that in control group (23.9 +/- 3.8 vs. 100 +/- 14.4, P<0.05). VEGF-A,
      -B, and -C contents in cell media of treatment group were significantly lower
      than those in control group (P<0.05). It was suggested that Pin1 inhibitor
      Juglone can effectively inhibit the proliferation, migration and the angiogenic
      ability of MCF7Adr cells, and can be used as an alternative drug therapy for
      breast cancer.

PMID- 26223923
TI  - Synergistic suppressive effect of PARP-1 inhibitor PJ34 and HDAC inhibitor SAHA
      on proliferation of liver cancer cells.
AB  - Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors and histone deacetylase (HDAC)
      inhibitors have recently emerged as promising anticancer drugs. The aim of this
      study was to investigate the effect of combination treatment with the PARP
      inhibitor PJ34 and HDAC inhibitor SAHA on the proliferation of liver cancer
      cells. Cell proliferation and apoptosis were assessed in three human liver cancer
      cell lines (HepG2, Hep3B and HCC-LM3) treated with PJ34 (8 MUmol/L) and SAHA (1
      MUmol/L), alone or combined, by Cell Counting Kit-8 assay and flow cytometry,
      respectively. The nude mice bearing subcutaneous HepG2 tumors were administered
      different groups of drugs (10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34+25 mg/kg
      SAHA), and the inhibition rates of tumor growth were compared between groups. The
      results showed that combined use of PJ34 and SAHA could synergistically inhibit
      the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The
      apoptosis rate of HepG2 cells treated with PJ34+SAHA was significantly higher
      than that of HepG2 cells treated with PJ34 or SAHA alone (P<0.05). In vivo, the
      tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34+SAHA
      groups, respectively. The combined use of PJ34 and SAHA could significantly
      inhibit the xenograft tumor growth when compared with use of PJ34 or SAHA alone
      (P<0.05). It was led to conclude that PJ34 and SAHA can synergistically suppress
      the proliferation of liver cancer cells. 

PMID- 26223924
TI  - Long non-coding RNA MEG3 induces renal cell carcinoma cells apoptosis by
      activating the mitochondrial pathway.
AB  - This study aimed to examine the effect of long non-coding RNA (LncRNA) MEG3 on
      the biological behaviors of renal cell carcinoma (RCC) cells 786-0 and the
      possible mechanism. MEG3 expression levels were detected by RT-qPCR in tumor
      tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786
      0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 (MEG3
      overexpression plasmid) and GV144 (control plasmid) were stably transfected into
      786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT,
      cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining,
      apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT
      qPCR in the transfected cells. The results showed that MEG3 was evidently
      downregulated in RCC tissues (P<0.05) and RCC cell lines (P<0.05). The
      viabilities of 786-0 cells were decreased significantly after transfection with
      GV144-MEG3 for over 24 h (P<0.05). Consistently, the apoptosis rate was
      significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h
      (P<0.05). Furthermore, overexpression of MEG3 could reduce the expression of Bcl
      2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein,
      and promote the release of cytochrome c protein to cytoplasm (P<0.05).
      Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression (P<0.05). It
      was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating
      the mitochondrial pathway.

PMID- 26223925
TI  - Effects of beta-catenin on differentially expressed genes in multiple myeloma.
AB  - This study aimed to identify the differentially expressed genes after silencing
      of beta-catenin in multiple myeloma transduced with beta-catenin shRNA. The DNA
      microarray dataset GSE17385 was downloaded from Gene Expression Omnibus,
      including 3 samples of MM1.S (human multiple myeloma cell lines) cells transduced
      with control shRNA and 3 samples of MM1.S cells transduced with beta-catenin
      shRNA. Then the differentially expressed genes (DEGs) were screened by using
      Limma. Their underlying functions were analyzed by employing Gene Ontology and
      Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Moreover,
      DEGs annotation was conducted based on the databases of tumor associated genes,
      tumor suppressed genes and the transcriptional regulation from patterns to
      profiles. Furthermore, the protein-protein interaction (PPI) relationship was
      obtained from STRING and the protein-protein interaction network and the
      functional modules were visualized by Cytoscape. Then, the pathway enrichment for
      the DEGs in the functional module was performed. A total of 301 DEGs, including
      124 up-regulated and 117 down-regulated DEGs, were screened. Functional
      enrichment showed that CCNB1 and CDK1 were significantly related to the function
      of cell proliferation. FOS and JUN were related to innate immune response
      activating signal transduction. Pathway enrichment analysis indicated that CCNB1
      and CDK1 were most significantly enriched in the pathway of cell cycle. Besides,
      FOS and JUN were significantly enriched in the Toll-like receptor signaling
      pathway. FOXM1 was identified as a transcription factor. Moreover, there existed
      interactions among CCNB1, FOXM1 and CDK1 in PPI network. The expression of FOS,
      JUN, CCNB1, FOXM1 and CDK1 may be affected by beta-catenin in multiple myeloma. 

PMID- 26223926
TI  - Serum sex hormone levels in different severity of male adult obstructive sleep
      apnea-hypopnea syndrome in East Asians.
AB  - Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a serious health issue,
      which can impact the hormone secretion. The aim of this study is to analyze the
      relationship between serum sex hormone concentrations and different severity
      degree of OSAHS, and to evaluate the influence of OSAHS on sex hormone levels. We
      enrolled 116 subjects who were subjected to polysomnography (PSG). They were
      divided into three groups: control group (n=10) [apnea hypopnea index (AHI)
      <5/h], mild-moderate OSAHS group (n=15) (5<=AHI<30/h), and severe OSAHS group
      (n=91) (AHI>=30/h). The patients in OSAHS group were subdivided into obesity and
      non-obesity subgroups. The parameters such as AHI, body mass index (BMI), lowest
      oxygen saturation (LSaO2), and mean oxygen saturation (MSaO2) were recorded.
      Serum levels of testosterone, polactin, estradiol, follicle stimulating hormone
      (FSH) and luteinizing hormone (LH) were determined in the morning immediately
      after waking up. Mean levels of hormones were compared among groups. The
      correlation between hormone levels and sleep-breathing parameters was analyzed.
      No significant differences in serum sex hormone levels were found among control,
      mild-moderate OSAHS, and severe OSAHS groups (P>0.05). There was no correlation
      between AHI and sex hormone levels (P>0.05). Testosterone was significantly
      negatively correlated with BMI (P<0.05). These results suggested that BMI might
      have a direct effect on testosterone level, and it might be an important factor
      affecting testosterone level in male OSAHS patients, and there may be no
      correlation between severity of OSAHS and sex hormones levels.

PMID- 26223927
TI  - Management of sphenoidal sinus lesions by septal-assisted approach: Surgical
      skills and advantages.
AB  - The aim of this study was to develop a less invasive trans-septal approach for
      the endoscopic management of sphenoid sinus lesions. We performed a septal
      assisted surgical procedure for endoscopic sphenoidectomy in 38 patients with
      isolated or combined sphenoidal sinus lesions, including fungal balls, mucoceles,
      purulent cystic sphenoidal sinusitis, etc. The posterior portion of the nasal
      septum became flexible after removal of the vomer and the sphenoidal rostrum. The
      superior portion of the common meatus was expanded to accommodate the endoscope
      after the septum was repositioned contra-laterally. The lesions were individually
      managed through the enlarged ostiums while damage to the mucosa of the front
      sphenoidal wall was avoided. All the procedures were completed successfully
      without intraoperative complications, and the bony ostiums were identified easily
      and enlarged accurately. During the follow-up period of 16 weeks to 2 years, no
      re-atresia or restenosis was observed. The recurrence rate was 0. No
      postoperative complications were recorded. All the responses from the patients
      were satisfactory. It was concluded that endoscopic sphenoidectomy assisted by
      trans-septal approach is a feasible, safe, effective and minimally invasive
      approach for selected cases with unilateral or bilateral lesions in the sphenoid
      sinuses. 

PMID- 26223928
TI  - Novel application of vacuum sealing drainage with continuous irrigation of
      potassium permanganate for managing infective wounds of gas gangrene.
AB  - Traumatic gas gangrene is a fatal infection mainly caused by Clostridium
      perfringens. It is a challenge to manage gas gangrene in open wounds and control
      infection after debridement or amputation. The aim of the present study was to
      use vacuum sealing drainage (VSD) with continuous irrigation of potassium
      permanganate to manage infective wounds of gas gangrene and observe its clinical
      efficacy. A total of 48 patients with open traumatic gas gangrene infection were
      included in this study. Amputations were done for 27 patients, and limb salvage
      procedures were performed for the others. After amputation or aggressive
      debridement, the VSD system, including polyvinyl alcohol (PVA) foam dressing and
      polyurethane (PU) film, with continuous irrigation of 1:5000 potassium
      permanganate solutions, was applied to the wounds. During the follow-up, all the
      patients healed without recurrence within 8-18 months. There were four
      complications. Cardiac arrest during amputation surgery occurred in one patient
      who suffered from severe septic shock. Emergent resuscitation was performed and
      the patient returned to stable condition. One patient suffered from mixed
      infection of Staphylococcal aureus, and a second-stage debridement was performed.
      One patient suffered from severe pain of the limb after the debridement.
      Exploratory operation was done and the possible reason was trauma of a local
      peripheral nerve. Three cases of crush syndrome had dialysis treatment for
      concomitant renal failure. In conclusion, VSD can convert open wound to closed
      wound, and evacuate necrotic tissues. Furthermore, potassium permanganate
      solutions help eliminate anaerobic microenvironment and achieve good therapeutic
      effect on gas gangrene and mixed infection. VSD with continuous irrigation of
      potassium permanganate is a novel, simple and feasible alternative for severe
      traumatic open wounds with gas gangrene infection. 

PMID- 26223929
TI  - Initial CT-guided percutaneous biopsy of vertebral lesions: Evaluation of its
      diagnostic accuracy and clinical value.
AB  - This study aimed to examine the diagnostic accuracy and clinical efficacy of
      initial CT-guided percutaneous biopsy of the vertebral lesions. A total of 305
      percutaneous biopsies of the vertebral lesions were performed under either CT
      guidance (n=127) or C-arm guidance (n=178). The diagnostic accuracy rate was
      evaluated by comparing the histopathological diagnosis with the ultimate
      diagnosis. The histopathological diagnosis was consistent with the ultimate
      diagnosis in 108 (85.0%, 108/127) cases of CT-guided biopsy and in 135 (75.8%,
      135/178) cases of C-arm guided biopsy and there was a significant difference. The
      accuracy of diagnosis based on biopsies varied with different diseases, including
      primary benign or malignant tumors, metastatic tumors, inflammatory lesions and
      fractures. A second biopsy or further examinations were required for patients
      with negative result obtained in the initial biopsy. The complication rate was
      3.1% (4/127) in CT-guided biopsy and 7.3% (13/178) in C-arm guided biopsy. In
      conclusion, CT-guided percutaneous biopsy is an accurate and safe technique for
      biopsy of the vertebral lesions. 

PMID- 26223930
TI  - Left ventricular systolic intraventricular flow field assessment in
      hyperthyroidism patients using vector flow mapping.
AB  - Intraventricular hydrodynamics is considered an important component of cardiac
      function assessment. Vector flow mapping (VFM) is a novel flow visualization
      method to describe cardiac pathophysiological condition. This study examined use
      of new VFM and flow field for assessment of left ventricular (LV) systolic
      hemodynamics in patients with simple hyperthyroidism (HT). Thirty-seven simple HT
      patients were enrolled as HT group, and 38 gender- and age-matched healthy
      volunteers as control group. VFM model was used to analyze LV flow field at LV
      apical long-axis view. The following flow parameters were measured, including
      peak systolic velocity (Vs), peak systolic flow (Fs), total systolic negative
      flow (SQ) in LV basal, middle and apical level, velocity gradient from the apex
      to the aortic valve (DeltaV), and velocity according to half distance (V1/2). The
      velocity vector in the LV cavity, stream line and vortex distribution in the two
      groups were observed. The results showed that there were no significant
      differences in the conventional parameters such as left ventricular ejection
      fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and left atrium
      diameter (LAD) between HT group and control group (P>0.05). Compared with the
      control group, a brighter flow and more vortexes were detected in HT group. Non
      uniform distribution occurred in the LV flow field, and the stream lines were
      discontinuous in HT group. The values of Vs and Fs in three levels, SQ in middle
      and basal levels, DeltaV and V1/2 were higher in HT group than in control group
      (P<0.01). DeltaV was positively correlated with serum free thyroxin (FT4)
      (r=0.48, P<0.01). Stepwise multiple regression analysis showed that LVEDD, FT4,
      and body surface area (BSA) were the influence factors of DeltaV. The unstable
      left ventricular systolic hydrodynamics increased in a compensatory manner in
      simple HT patients. The present study indicated that VFM may be used for early
      detection of abnormal ventricle contraction in clinical settings. 

PMID- 26223931
TI  - Laser-induced interstitial thermotherapy via a single-needle delivery system:
      Optimal conditions of ablation, pathological and ultrasonic changes.
AB  - This study aimed to examine the optimal conditions of laser-induced interstitial
      thermotherapy (LITT) via a single-needle delivery system, and the ablation
      related pathological and ultrasonic changes. Ultrasound (US)-guided LITT
      (EchoLaser system) was performed at the output power of 2-4 Wattage (W) for 1-10
      min in ex vivo bovine liver. Based on the results of the ex vivo study, the
      output power of 3 and 4 W with different durations was applied to in vivo rabbit
      livers (n=24), and VX2 tumors implanted in the hind limbs of rabbits (n=24). The
      ablation area was histologically determined by hematoxylin-eosin (HE) staining.
      Traditional US and contrast enhanced ultrasound (CEUS) were used to evaluate the
      treatment outcomes. The results showed: (1) In the bovine liver, ablation
      disruption was grossly seen, including a strip-like ablation crater, a
      carbonization zone anteriorly along the fiber tip, and a surrounding gray-white
      coagulation zone. The coagulation area, 1.2 cm in length and 1.0 cm in width, was
      formed in the bovine liver subjected to the ablation at 3 W for 5 min and 4 W for
      4 min, and it extended slightly with the ablation time. (2) In the rabbit liver,
      after LITT at 3 W for 3 min and more, the coagulation area with length greater
      than or equal to 1.2 cm, and width greater than or equal to 1.0 cm, was found.
      Similar coagulation area was seen in the implanted VX2 carcinoma at 3 W for 5
      min. (3) Gross examination of the liver and carcinoma showed three distinct
      regions: ablation crater/carbonization, coagulation and congestion distributed
      from the center outwards. (4) Microscopy revealed four zones after LITT,
      including ablation crater/carbonization, coagulation, edema and congestion from
      the center outwards. A large area with coagulative necrosis was observed around a
      vessel in the peripheral area with edema and hyperemia. (5) The size of
      coagulation was consistent well to the CEUS findings. It was concluded that
      EchoLaser system at low power can produce a coagulation area larger than 1.0
      cm*1.0 cm during a short time period. The real-time US imaging can be used to
      effectively guide and assess the treatment. 

PMID- 26223932
TI  - Nucleus transfer efficiency of ear fibroblast cells isolated from Bama miniature
      pigs at various ages.
AB  - Somatic cell nucleus transfer (SCNT) has been considered the most effective
      method for conserving endangered animals and expanding the quantity of adult
      animal models. Bama miniature pigs are genetically stable and share similar
      biological features to humans. These pigs have been used to establish animal
      models for human diseases, and for many other applications. However, there is a
      paucity of studies on the effect of ear fibroblasts derived from different age of
      adult Bama miniature pigs on nucleus transfer (NT). The present study examined
      the NT efficiency of ear fibroblasts from fetal, newborn, 1-, 2-, 4-, 6-, 12
      month-old miniature pigs by using trypan blue staining, flow cytometry and NT
      technique, etc., and the cell biological function and SCNT efficiency were
      compared between groups. The results showed that ear fibroblasts grew well after
      passage in each group. Spindle-shaped cells initially predominated, and gradually
      declined with increase of culture time and replaced by polygonal cells. Irregular
      cell growth occurred in the 2-month-old group and the elder groups. The growth
      curves of the ear fibroblasts were "S-shaped" in different age groups. The cell
      proliferation of postnatal ear fibroblasts, especially those from 2-, 4-, 6-, 12
      month-old miniature pigs was significantly different from that of fetus ear
      fibroblasts (P<0.05 or P<0.01). Two-month- and 4-month-old ear fibroblasts had a
      significantly higher proportion of G1 stage cells (85% to 91%) than those at 6
      and 12 months (66% to 74%, P<0.01). The blastocyst rate of reconstructed embryos
      originating from newborn, 1-, 2-, 4-month-old donor pigs was 6.06% to 7.69% with
      no significant difference from that in fetus fibroblast group (8.06%). It was
      concluded that <4-month-old adult Bama miniature pigs represent a better donor
      cell resource than elder pigs. 

PMID- 26223933
TI  - BRAF(V600E) mutation and its association with clinicopathological features of
      papillary thyroid microcarcinoma: A meta-analysis.
AB  - Recent studies have demonstrated that the BRAF(V600E) mutation is associated with
      aggressive clinicopathological features of papillary thyroid carcinoma (PTC).
      However, the BRAF mutation as a prognostic biomarker in papillary thyroid
      microcarcinoma (PTMC) is unclear. A systematic search of the electronic
      databases, including Medline, Scopus, CNKI and the Cochrane Library was performed
      up to July 1, 2014. Outcomes of interest included age, gender, concomitant
      hashimoto thyroiditis or nodular goiter, tumor size, pathological stage, tall
      cell variant of PTMC (TCVPTMC), multifocality, extrathyroidal extension (ETE) and
      lymph node metastasis (LNM). A total of 19 studies published from 2008 to 2014
      comprising 2253 patients fulfilled the inclusion criteria and were included in
      the meta-analysis, and 1143 (50.7%) of these patients were BRAF mutation
      positive. BRAF mutation was associated with larger tumor size (OR: 1.64; 95% CI:
      1.16-2.32), multifocality (OR: 1.58; 95% CI: 1.25-2.00), ETE (OR: 2.59; 95% CI:
      2.03-3.29), LNM (OR: 1.73; 95% CI: 1.14-2.62), advanced stage (OR: 2.03; 95% CI:
      1.14-3.64) and TCVPTMC (OR: 5.07; 95% CI: 1.49-17.27; P=0.009). Additionally, the
      BRAF mutation was found to be not associated with age, gender, concomitant
      hashimoto thyroiditis or nodular goiter (P>0.05 for all). This meta-analysis
      revealed that in patients with PTMC, BRAF mutation is associated with tumor size,
      multifocality, ETE, LNM, advanced stage and TCVPTMC, and it may be used as a
      predictive factor for prognosis of PTMC.

PMID- 26223934
TI  - Management of the middle hepatic vein in right lobe living donor liver
      transplantation: A meta-analysis.
AB  - Living donor liver transplantation (LDLT) is a curative treatment for end stage
      liver disease. It is advantageous due to the shortage of deceased donors.
      However, in LDLT, whether the middle hepatic vein (MHV) should be preserved in
      donors remains controversial. We conducted searches in Pubmed, Embase, Cochrane
      Library, Web of Science, Ovid, and Google Scholar using the key words "living
      donor liver transplantation" and "middle hepatic vein". Due to ethical issues,
      there were no randomized control trails focusing on MHV in LDLT. The majority of
      reports were retrospective studies. We examined the reference lists to identify
      related investigations. Google Scholar was then used to obtain full texts. Nine
      observational studies were analyzed. There were no significant differences in
      liver function (WMD, -5.51; P=0.12) and complications (RR, 0.98; P=0.89) in
      donors with or without MHV. However, the liver function in recipients was greatly
      improved after LDLT with MHV (WMD, -78.32; P=0.01). No definite conclusion was
      obtained in terms of the liver regeneration indices between LDLT with or without
      MHV. It was conclude that grafts with MHV in LDLT favor recipient outcomes and do
      not harm the living donor if a careful preoperative evaluation is performed. 

PMID- 26223935
TI  - Health disparities among the western, central and eastern rural regions of China
      after a decade of health promotion and disease prevention programming.
AB  - Health disparities between the western, central and eastern regions of rural
      China, and the impact of national health improvement policies and programming
      were assessed. A total of 400 counties were randomly sampled. ANOVA and Logistic
      regression modeling were employed to estimate differences in health outcomes and
      determinants. Significant differences were found between the western, central and
      eastern rural regions in community infrastructure and health outcomes. From 2000
      to 2010, health indicators in rural China were improved significantly, and the
      infant mortality rate (IMR), maternal mortality rate (MMR) and under 5 mortality
      rate (U5MR) had fallen by 62.79%, 71.74% and 61.92%, respectively. Central rural
      China had the greatest decrease in IMR (65.05%); whereas, western rural China had
      the greatest reduction in MMR (72.99%) but smallest reduction in U5MR (57.36%).
      Despite these improvements, Logistic regression analysis showed regional
      differences in key health outcome indicators (odds ratios): IMR (central: 2.13;
      western: 5.31), U5MR (central: 2.25; western: 5.69), MMR (central: 1.94; western:
      3.31), and prevalence of infectious diseases (central: 1.62; western: 3.58). The
      community infrastructure and health outcomes of the western and central rural
      regions of China have been improved markedly during the first decade of the 21st
      century. However, health disparities still exist across the three regions.
      National efforts to increase per capita income, community empowerment and
      mobilization, community infrastructure, capacity of rural health facilities, and
      health literacy would be effective policy options to attain health equity. 

PMID- 26223936
TI  - Systematic review: bile acids and intestinal inflammation-luminal aggressors or
      regulators of mucosal defence?
AB  - BACKGROUND: Inflammatory bowel diseases (IBD), comprising Crohn's disease and
      ulcerative colitis (UC), are chronic conditions attributed to an aberrant immune
      response to luminal triggers. Recently, published work suggests a pathogenic role
      for bile acids in this context. AIM: To perform a systematic review of studies
      investigating the role of bile acids in intestinal inflammation and present
      potentially relevant clinical implications. METHODS: Pubmed search for English
      language articles published up to May 2015. Terms used were: 'bile', 'bile acid',
      'barrier', 'small bowel injury', 'Crohn's' and 'colitis'. RESULTS: Experimental
      studies support a variable role for bile acids in intestinal barrier
      homoeostasis. This may be attributed to different physicochemical properties,
      variable effects on epithelia and immune cells via bile acids-specific receptors,
      or through a cross-talk with the gut microbiome. A reduction in the bile acids
      pool, with lower concentrations of secondary forms, has been recognised for some
      time in Crohn's disease and associated to ileal dysfunction and bile acids
      malabsorption. Recent work suggests that these changes, including an increase in
      sulphated forms, are related to inflammatory activity in both Crohn's disease and
      UC. The detrimental effects of 'western diet' elements such as emulsifiers and
      fat, which have been implicated in the development of the current IBD and obesity
      epidemics, may also be bile acid-mediated. CONCLUSIONS: Although there are only a
      few observational clinical studies to support an interaction, in vivo human and
      animal studies support an association between bile acids metabolism, the gut
      microbiome and intestinal inflammation. This may well prove to have significant
      diagnostic and therapeutic implications.

PMID- 26223937
TI  - DNA Analysis and Document Examination: The Impact of Each Technique on Respective
      Analyses.
AB  - Threatening letters, counterfeit documents, and anonymous notes can commonly be
      encountered in criminal situations. Such handwritten documents may encourage DNA
      to transfer from the writer's hands and lower arms when these areas come into
      contact with the document. As any DNA transferred is likely to be at a low level,
      sensitive low copy number (LCN) DNA analysis can be employed for testing document
      exhibits. In this study, we determine locations on the document that are most
      commonly touched during writing and handling and compare DNA recovery from these
      sites. We describe the impact of DNA sampling on subsequent document examination
      techniques including the ESDA((r)) and likewise the effect of the ESDA((r)) and
      two other document examination techniques on subsequent DNA analysis. The
      findings from this study suggest that DNA results can be obtained through
      targeted sampling of document evidence, but that care is required when ordering
      these examination strategies. 

PMID- 26223938
TI  - Salivary Gland Epithelial-Myoepithelial Carcinoma with High-Grade Transformation
      in a Dog.
AB  - An 8-year-old male neutered standard dachshund was presented with a slowly
      growing mass in the left submandibular salivary gland. Histopathological
      examination revealed a tumour that was composed of bilayered duct-like structures
      with an inner layer of ductal cells and an outer layer of clear cells. Both inner
      and outer cells in the greater part of the tumour exhibited low to moderate
      atypia and low mitotic activity. However, a focal area towards the periphery
      showed enhanced cellular atypia and mitotic activity in tumour cells.
      Immunohistochemically, the outer layer of clear cells expressed myoepithelial
      markers, while the inner layer cells were positive for a luminal epithelial
      marker. No local recurrence or lymph node or distant metastasis was observed 18
      months following surgery. Based on the morphology and immunohistochemical
      findings, a final diagnosis of epithelial-myoepithelial carcinoma with high-grade
      transformation was made. 

PMID- 26223939
TI  - Epidural analgesia does not influence anastomotic leakage incidence after open
      colorectal surgery for cancer: A retrospective study on 1,474 patients.
AB  - BACKGROUND: Anastomotic leakage is a major cause of morbidity after colorectal
      surgery. Epidural analgesia is the most effective method for postoperative pain
      relief after major abdominal surgery. Anyhow, its effect on anastomotic leakage
      rate is still controversial. This study aimed to compare epidural versus
      intravenous analgesia as risk factor for anastomotic leakage requiring
      reoperation in patients undergoing open colorectal surgery for cancer. METHODS: A
      retrospective study on 1,474 patients was performed. The Cox proportional hazards
      model was used to study the relation between primary and secondary factors of
      risk and anastomotic leakage occurrence within 30 days after elective operation.
      RESULTS: Overall 30-day anastomotic leakage requiring reoperation was 4.9%
      (95%CI: 3.8-6.0%). No difference in anastomotic leakage occurrence was observed
      between the epidural analgesia group and the intravenous analgesia group (Hazard
      ratio: 0.94; 95%CI: 0.53-1.67%; P = 0.8338). Females had a rate of anastomotic
      leakage 43% lower than males (P = 0.0301). The diverting stoma resulted to be
      protective for anastomotic leakage occurrence (P = 0.0052). AL significantly
      increased postoperative median length of stay but not in-hospital mortality.
      CONCLUSIONS: Epidural analgesia does not influence the AL risk after open
      colorectal surgery for cancer.

PMID- 26223940
TI  - Decrease of mRNA Editing after Spinal Cord Injury is Caused by Down-regulation of
      ADAR2 that is Triggered by Inflammatory Response.
AB  - We recently showed that spinal cord injury (SCI) leads to a decrease in mRNA
      editing of serotonin receptor 2C (5-HT2CR) contributing to post-SCI spasticity.
      Here we study post-SCI mRNA editing and global gene expression using massively
      parallel sequencing. Evidence is presented that the decrease in 5-HT2CR editing
      is caused by down-regulation of adenosine deaminase ADAR2 and that editing of at
      least one other ADAR2 target, potassium channel Kv1.1, is decreased after SCI.
      Bayesian network analysis of genome-wide transcriptome data indicates that down
      regulation of ADAR2 (1) is triggered by persistent inflammatory response to SCI
      that is associated with activation of microglia and (2) results in changes in
      neuronal gene expression that are likely to contribute both to post-SCI
      restoration of neuronal excitability and muscle spasms. These findings have broad
      implications for other diseases of the Central Nervous System and could open new
      avenues for developing efficacious antispastic treatments. 

PMID- 26223941
TI  - Acute Effects of a Glucagon-Like Peptide 2 Analogue, Teduglutide, on
      Gastrointestinal Motor Function and Permeability in Adult Patients With Short
      Bowel Syndrome on Home Parenteral Nutrition.
AB  - BACKGROUND: Glucagon-like peptide 2 (GLP-2) agonists decrease the need for
      parenteral nutrition (PN) in short bowel syndrome (SBS); mechanisms evaluated to
      date have focused on the intestinotrophic effect of GLP-2 agonists such as
      increased absorptive capacity of the remnant intestine and increased citrulline
      levels. Other mechanisms may also play a role in effects of GLP-2 agonists. AIM:
      To measure effects of a GLP-2 agonist, teduglutide (TED), compared with placebo
      (PLA) on gastric emptying (GE), overall gut transit, fluid balance, intestinal
      monosaccharide absorption, and permeability in patients with SBS on home PN
      (HPN). MATERIALS AND METHODS: In 8 adults with SBS on HPN, we compared daily
      subcutaneous TED (0.05 mg/kg) and PLA (crossover design, each treatment 7 days
      with a 14-day washout) on gut transit, intestinal absorption, and permeability
      after oral mannitol (200 mg) and lactulose (1 g), as well as stool weight and
      urine volume over 8 hours. Analysis used the paired t test. RESULTS: Of 8
      patients, 4 were men, with a mean +/- SD age of 54 +/- 1 years, body mass index
      of 25 +/- 4 kg/m2, residual small intestine of 63 +/- 12 cm, and 25% +/- 15% of
      residual colon. The overall gut transit (% emptied at 6 hours) was 53.4% +/- 15%
      for TED vs 62.4% +/- 15.2% for PLA (P = .075), with no effect on GE (P = .74).
      TED increased urine mannitol excretion at 0-2 hours (16.2 +/- 3.6 mg TED vs 11.3
      +/- 2.2 mg PLA, P = .20) and 0-8 hours (32.7 +/- 5.9 mg PLA vs 48.8 +/- 8.9 mg
      TED, P = .17). There were no differences in urine lactulose excretion or
      lactulose/mannitol ratio (0.024 +/- 0.005 TED vs 0.021 +/- 0.005 PLA). Over 8
      hours, TED (vs PLA) numerically reduced stool weight (mean +/- SEM, 77 +/- 18 g
      TED vs 106 +/- 43 g PLA, P = .42) and increased urine volume (408.9 +/- 52.2 mL
      TED vs 365.7 +/- 57.3 mL PLA, P = .34). CONCLUSION: Seven-day TED treatment in 8
      participants suggests beneficial effects on fluid balance and monosaccharide
      absorption, and it retarded overall gut transit with no effects on GE or mucosal
      permeability. Larger, longer, mechanistic studies of TED in SBS are warranted.
      This trial was registered at clinicaltrials.gov as NCT02099084.

PMID- 26223942
TI  - omega-3 Fatty Acids Reduce Chemotherapy-Induced Hematological Toxicity by Bone
      Marrow Stimulation in Mice.
AB  - BACKGROUND: omega-3 Fatty acids exert several benefits during chemotherapy, such
      as preventing intestinal mucosal damage and improving response to chemotherapy.
      However, little is known about the effect of omega-3 fatty acids on chemotherapy
      induced hematological toxicities. METHODS: Mice that had consumed either an omega
      3-rich or an omega-3-poor diet for 2 weeks were intraperitoneally administered
      cisplatin. The resultant changes in blood cell count, bone marrow cell count, and
      cytokine levels in bone marrow supernatant were analyzed. The effect of omega-3
      fatty acids on human peripheral blood mononuclear cells (PBMCs) exposed to
      cisplatin was also examined. RESULTS: Although peripheral blood cell counts
      decreased after cisplatin treatment in both groups of mice, the decrease in white
      blood cell count was significantly lower in mice that consumed the omega-3-rich
      diet. The decrease in bone marrow cells after cisplatin treatment was also
      reduced in mice that consumed the omega-3-rich diet. Levels of stem cell factor
      (SCF) and fibroblast growth factor 1 (FGF-1) were significantly higher in bone
      marrow supernatants from mice that consumed the omega-3-rich diet. The rate of
      apoptosis in PBMCs (after exposure to cisplatin) cultured in medium containing
      omega-3 fatty acids was significantly lower than in PBMCs cultured in control
      medium. CONCLUSION: omega-3-Rich diets reduced chemotherapy-induced leukopenia in
      mice. This may be the result of increased numbers of bone marrow cells due to
      higher levels of SCF and FGF-1 in the bone marrow.

PMID- 26223943
TI  - Biological approaches to treating intervertebral disk degeneration: devising stem
      cell therapies.
AB  - Intervertebral disk (IVD) degeneration is a common, chronic, and complex
      degeneration process that frequently leads to back pain and disability, resulting
      in a major public health issue. In this review we describe biological therapies
      under preclinical or clinical development with an emphasis on stem cell-based
      multimodal approaches that target prevention and treatment of IVD degeneration.
      Systematical review of the basic science and clinical literature was performed to
      summarize the current status of devising biological approaches to treating IVD
      degeneration. Since the exact mechanisms underlying IVD degeneration have not yet
      been fully elucidated and conservative managements appear to be mostly
      ineffective, current surgical treatment focuses on removal of the pathological
      disk tissues combined with spinal fusion. The treatment options, however, often
      produce insufficient efficacy and even serious complications. Therefore, there
      have been growing demands and endeavors for developing novel regenerative biology
      guided strategies for repairing the IVD via delivery of exogenous growth factors,
      introduction of therapeutic genes, and transplantation of stem cells, or
      combinatorial therapies. Overall, the data suggest that when applied under a
      recovery neurobiology principle, multimodal regimens comprising ex vivo
      engineered stem cell-based disks hold a high potential promise for efficacious
      clinical translations. 

PMID- 26223944
TI  - 7-endo selenocyclization reactions on chiral 3-prenyl and 3-cinnamyl-2
      hydroxymethylperhydro-1,3-benzoxazine derivatives. A way to enantiopure 1,4
      oxazepanes.
AB  - Enantiopure 1,4-oxazepane derivatives have been prepared by
      selenocyclofunctionalization of chiral 3-prenyl- and 3-cinnamyl-2-hydroxymethyl
      substituted perhydro-1,3-benzoxazine derivatives. The 7-endo-cyclization occurs
      in high yields and diastereoselection. The regio- and stereochemistry of the
      cyclization products was dependent on the substitution pattern of the double
      bond, the nature of the hydroxyl group and the experimental conditions. 

PMID- 26223945
TI  - Influence of UDP-Glucuronosyltransferase Polymorphisms on Stable Warfarin Doses
      in Patients with Mechanical Cardiac Valves.
AB  - AIM: This study aimed to evaluate the effect of uridine diphosphate (UDP)
      glucuronosyltransferase (UGT) polymorphisms on warfarin dosing requirements in
      patients with mechanical cardiac valves. METHODS: A total of 191 patients with
      stable warfarin doses from the EAST Group of Warfarin were included in this
      study. The influence of genetic polymorphisms on stable warfarin doses was
      investigated by genotyping 6 single nucleotide polymorphisms (SNPs): vitamin K
      epoxide reductase complex 1 (VKORC1) rs9934438, cytochrome P450 (CYP) 2C9
      rs1057910, CYP4F2 rs2108622, and UGT1A1 (rs887829, rs4148323, and rs4124874). An
      additional subgroup analysis was carried out using patients with wild-type
      homozygote carriers of CYP2C9. RESULTS: One UGT1A1 SNP of rs887829 (C>T)
      exhibited significant association with stable warfarin doses in the study
      population and subgroup. Patients with the T allele in UGT1A1 rs887829 (CT or TT)
      required higher doses than those with the CC genotype in the study population
      (6.3 +/- 2.4 mg vs. 5.2 +/- 1.6 mg, P = 0.003). Similarly, in the subpopulation
      of AA carriers in the CYP2C9 gene, patients with the T allele required
      significantly higher doses of warfarin than those with other genotypes of
      rs887829 (6.5 +/- 2.4 vs. 5.3 +/- 1.5 mg, P = 0.002). Approximately 45.1% of
      overall interindividual variability in warfarin dose requirement was explained by
      the multivariate regression model. VKORC1, CYP2C9, UGT1A1 rs887829, age, and
      CYP4F2 accounted for 28.2%, 6.6%, 5.5%, 3.0%, and 1.8% of the variability,
      respectively. CONCLUSION: Our results suggest that UGT1A1 could be a determinant
      of stable warfarin doses.

PMID- 26223946
TI  - Movement Analysis of Flexion and Extension of Honeybee Abdomen Based on an
      Adaptive Segmented Structure.
AB  - Honeybees (Apis mellifera) curl their abdomens for daily rhythmic activities.
      Prior to determining this fact, people have concluded that honeybees could curl
      their abdomen casually. However, an intriguing but less studied feature is the
      possible unidirectional abdominal deformation in free-flying honeybees. A high
      speed video camera was used to capture the curling and to analyze the changes in
      the arc length of the honeybee abdomen not only in free-flying mode but also in
      the fixed sample. Frozen sections and environment scanning electron microscope
      were used to investigate the microstructure and motion principle of honeybee
      abdomen and to explore the physical structure restricting its curling. An
      adaptive segmented structure, especially the folded intersegmental membrane
      (FIM), plays a dominant role in the flexion and extension of the abdomen. The
      structural features of FIM were utilized to mimic and exhibit movement
      restriction on honeybee abdomen. Combining experimental analysis and theoretical
      demonstration, a unidirectional bending mechanism of honeybee abdomen was
      revealed. Through this finding, a new perspective for aerospace vehicle design
      can be imitated. 

PMID- 26223947
TI  - Identification of Core Alpha 1,3-Fucosyltransferase Gene From Silkworm: An Insect
      Popularly Used to Express Mammalian Proteins.
AB  - Silkworm has great potential as production system of recombinant mammalian
      proteins. When the protein products are used for medical purpose, it is required
      to reduce the risk of an allergy, the content of core alpha 1,3-fucosyl residue
      attached to the N-glycan of proteins, for example. We isolated the gene of an
      enzyme responsible for the transfer of core alpha 1,3-fucosyl residue, core alpha
      1,3-fucosyltransferase (Fuc-T C3), from silkworm. A candidate cDNA for silkworm
      Fuc-T C3 was isolated as a homolog of the fruit fly enzyme gene fucTA. The gene
      was located on chromosome 7 of the silkworm genome and was composed of seven
      exons, which spanned approximately 10 kb on the genome. The coding region of the
      gene was 1,350 bp and encoded a 450-amino acid protein with a molecular mass of
      52.2 kDa. Deduced amino acid sequence of the coding region showed one
      transmembrane domain in its N-terminal and typical motifs common to
      fucosyltransferases including Fuc-T C3s of other organisms in its C-terminal. The
      extract of CHO cells transfected with the cDNA showed Fuc-T C3 activity using GDP
      fucose and DABS-GnGn peptide as substrates. These results showed this cDNA clone
      actually encodes silkworm Fuc-T C3. 

PMID- 26223948
TI  - Description of a New Species of the Genus Psectrosciara and a New Record of
      Parascatopse sonorensis (Diptera: Scatopsidae) From Florida.
AB  - Psectrosciara floridensis sp. nov. belonging to the scatopsiformis group is
      described and illustrated. This species is closely related to Psectrosciara
      scatopsiformis Enderlein, 1912, Psectrosciara californica (Cole, 1912),
      Psectrosciara brevipennis Cook, 1958, and Psectrosciara serrata Cook, 1958. A new
      record of Parascatopse sonorensis Cook is reported from the state of Florida. 

PMID- 26223949
TI  - Slowing the Spread of Grapevine Leafroll-Associated Viruses in Commercial
      Vineyards With Insecticide Control of the Vector, Pseudococcus maritimus
      (Hemiptera: Pseudococcidae).
AB  - Vineyards were surveyed for grapevine leafroll-associated viruses and their
      insect vectors in New York State's Finger Lakes region in 2006-2008. Grape
      mealybug, Pseudococcus maritimus (Erhorn) (Hemiptera: Pseudococcidae), European
      Fruit Lecanium, Parthenolecanium corni (Bouche), and Cottony Maple Scale,
      Pulvinaria acericola (Walsh and Riley) (Hemiptera: Coccidae) were identified as
      vector species in this region. An increase in the incidence of Grapevine leafroll
      associated virus 1 (GLRaV-1) and GLRaV-3 was observed in 8 of the 20 vineyards
      surveyed, which implies transmission by these insect vectors. Two of the
      vineyards for which a temporal increase in disease incidence was documented were
      then used to evaluate the efficacy of foliar applications of horticultural oil
      and two classes of insecticides for control of P. maritimus and for slowing virus
      spread over 2 years of vine protection. Delayed dormant applications of
      horticultural oil contributed to control of early season crawlers; however, this
      was not the case for control of summer populations. Applications of acetamiprid
      and spirotetramat achieved control in summer populations; however, spirotetramat
      outperformed acetamiprid in percent reduction of treated compared with control
      vines and in a side-by-side trial. Vines treated with spirotetramat had a lower
      percentage of new vines testing positive for GLRaV-1 than control vines after 2
      years, while no other spray program altered the increase in incidence of GLRaV-1
      or -3. 

PMID- 26223950
TI  - Histone H4 acetylation required for chromatin decompaction during DNA
      replication.
AB  - Faithful DNA replication is a prerequisite for cell proliferation. Several
      cytological studies have shown that chromosome structures alter in the S-phase of
      the cell cycle. However, the molecular mechanisms behind the alteration of
      chromosome structures associated with DNA replication have not been elucidated.
      Here, we investigated chromatin structures and acetylation of specific histone
      residues during DNA replication using the meiotic nucleus of the fission yeast
      Schizosaccharomyces pombe. The S. pombe meiotic nucleus provides a unique
      opportunity for measuring the levels of compaction of chromatin along the
      chromosome in a defined orientation. By direct measurement of chromatin
      compaction in living cells, we demonstrated that decompaction of chromatin occurs
      during meiotic DNA replication. This chromatin decompaction was suppressed by
      depletion of histone acetyltransferase Mst1 or by arginine substitution of
      specific lysine residues (K8 and K12) of histone H4. These results suggest that
      acetylation of histone H4 residues K8 and K12 plays a critical role in loosening
      chromatin structures during DNA replication. 

PMID- 26223952
TI  - Comparison and characterization of biosorption by Weissella viridescens MYU 205
      of periodic group 12 metal ions.
AB  - Because heavy metals cause various health hazards, we studied biosorption by
      Weissella viridescens MYU 205. MYU 205 showed high biosorption for Cd (II) and Hg
      (II) and was low for Zn (II). The Hg (II) biosorption rate was high at about 80%.
      Different biosorptions were shown for each metal after successive incubation.
      About 20% of the Zn (II) biosorption was observed after 3 h. Cd (II) biosorption
      increased in a time-dependent manner until 3 h, then gradually decreased. Hg (II)
      was immediately sorbed at 79.6 +/- 4.7% and decreased at 3 h to 52.9 +/- 2.6%,
      and then gradually increased to 77.8 +/- 3.6%. Using heat-killed cells, the rate
      of biosorption of Zn (II) and Cd (II) decreased whereas Hg (II) tended to
      increase. The metal resistance was high, that is Zn (II) > Cd (II) > Hg (II);
      while the affinity was opposite where MYU 205 showed high affinity to Hg (II) and
      low affinity to Zn (II). Our data shows lactic acid bacteria may be powerful
      heavy metal sorbents for detoxification. 

PMID- 26223951
TI  - Actin nucleation by WH2 domains at the autophagosome.
AB  - Autophagy is a catabolic process whereby cytosolic components and organelles are
      degraded to recycle key cellular materials. It is a constitutive process required
      for proper tissue homoeostasis but can be rapidly regulated by a variety of
      stimuli (for example, nutrient starvation and chemotherapeutic agents). JMY is a
      DNA damage-responsive p53 cofactor and actin nucleator important for cell
      survival and motility. Here we show that JMY regulates autophagy through its
      actin nucleation activity. JMY contains an LC3-interacting region, which is
      necessary to target JMY to the autophagosome where it enhances the autophagy
      maturation process. In autophagosomes, the integrity of the WH2 domains allows
      JMY to promote actin nucleation, which is required for efficient autophagosome
      formation. Thus our results establish a direct role for actin nucleation mediated
      by WH2 domain proteins that reside at the autophagosome. 

PMID- 26223953
TI  - [Shock wave lithotripsy in Germany: Results of a nationwide survey].
AB  - BACKGROUND: Following its introduction in the 1980s extracorporeal shock wave
      lithotripsy (SWL) became the gold standard for therapy of ureteral and renal
      calculi. The research data published during the last decade suggest a paradigm
      shift to endourological techniques. OBJECTIVES: The purpose of this study was to
      compare whether the suggested loss of status for SWL corresponds with actual real
      life treatment in Germany. A further aim was to assess the quality of SWL therapy
      in German hospitals. MATERIALS AND METHODS: The board of the German Society for
      Shock Wave Lithotripsy (DGSWL) sent a questionnaire to 306 urological departments
      in Germany, which encompassed medical, technical and organizational topics in the
      therapy of ureteral and renal calculi. A total of 99 (33%) questionnaires were
      returned. CONCLUSION: With the exception of a few departments, non-invasive SWL
      still plays a major role in the treatment of urolithiasis and a loss of the gold
      standard status is not in sight. The performance of SWL in German hospitals is
      carried out at a high level of quality. To maintain and optimize this status a
      structured SWL training and adherence to clinical practice guidelines are needed.

PMID- 26223954
TI  - [Sub-threshold prostate-specific antigen levels after resection of metachronous
      pulmonary metastases].
AB  - Radical prostatectomy is a curative therapy for prostate cancer with a lifetime
      follow-up because there is a high risk of recurrence, especially in the first
      years of follow-up. In our case disseminated metachronous pulmonary metastases
      were detected by imaging 4 years after prostatectomy because of elevated levels
      of serum prostate-specific antigen (PSA). After complete resection of the
      thoracic metastases the PSA levels have remained below the detection threshold
      with a recurrence-free survival of 24 months. This case demonstrates that the
      resection of pulmonary metastases may also be useful for specific individual
      patients with prostate cancer. 

PMID- 26223955
TI  - [Extracorporeal shock wave lithotripsy (ESWL) versus percutaneous nephrolithotomy
      (PCNL) or retrograde intrarenal surgery (RIRS) for kidney stones].

PMID- 26223956
TI  - Efficacy of Ginkgo biloba extract EGb 761(r) in dementia with behavioural and
      psychological symptoms: A systematic review.
AB  - OBJECTIVES: To review current evidence of efficacy of Ginkgo biloba extract EGb
      761(r) in dementia with behavioural and psychological symptoms (BPSD). METHODS:
      Randomized, placebo-controlled trials assessing the effects of EGb 761(r) in
      dementia patients with BPSD were included if the diagnosis was made in accordance
      with internationally accepted criteria, the treatment period was at least 22
      weeks, outcome measures covered BPSD and at least two of the following domains of
      assessment, i.e. cognition, activities of daily living and clinical global
      assessment, and methodological quality was adequate. An analysis of covariance
      (ANCOVA) model was used to calculate the pooled effect estimates and to compare
      effects of EGb 761(r) and placebo; furthermore, combined risk differences of
      response rates were calculated. RESULTS: Four published trials were identified,
      involving altogether 1,628 outpatients with mild to moderate dementia. Least
      square mean differences for change from baseline in cognition, BPSD (including
      caregiver distress rating), activities of daily living, clinical global
      impression, and quality of life favoured EGb 761(r) (P < 0.001 for all
      comparisons). CONCLUSIONS: The pooled analyses provide evidence of efficacy of
      EGb 761(r) at a daily dose of 240 mg in the treatment of out-patients suffering
      from Alzheimer's, vascular or mixed dementia with BPSD.

PMID- 26223957
TI  - Neuroinflammation in suicide: Toward a comprehensive model.
AB  - OBJECTIVES: Suicidal behaviour (SB) entered the DSM-5, underlying a specific
      biological vulnerability. Then, recent findings suggested a possible role of the
      immune system in SB pathogenesis. The objective of this review is to present
      these main immune factors involved in SB pathogenesis. METHODS: We conducted a
      review using Preferred Reporting Items for Systematic reviews and Meta-Analysis
      criteria, and combined ("Inflammation") AND ("Suicidal ideation" OR "Suicidal
      attempt" OR "suicide"). RESULTS: Post mortem studies demonstrated associations
      between suicide and inflammatory cytokines in the orbitofrontal cortex, a brain
      region involved in suicidal vulnerability. Also, microgliosis and monocyte
      macrophage system activation may be a useful marker of suicide neurobiology.
      Kynurenine may influence inflammatory processes, and related molecular pathways
      may be involved in SB pathophysiology. Few recent studies associated inflammatory
      markers with suicidal vulnerability: serotonin dysfunction, impulsivity and
      childhood trauma. Interestingly, the perception of threat that leads suicidal
      individuals to contemplate suicide may activate biological stress responses,
      including inflammatory responses. CONCLUSIONS: Translational projects would be
      crucial to identify a specific marker in SB disorders, to investigate its
      clinical correlations, and the interaction between inflammatory cytokines and
      monoamine systems in SB. These researches might lead to new biomarkers and novel
      directions for therapeutic strategies.

PMID- 26223958
TI  - Combined methylphenidate and atomoxetine pharmacotherapy in attention deficit
      hyperactivity disorder.
AB  - OBJECTIVES: Pharmacological treatment of attention deficit hyperactivity disorder
      (ADHD) includes stimulant and non-stimulant medications. Our purpose in this
      study is to investigate efficacy, safety and tolerability of combined
      methylphenidate and atomoxetine pharmacotherapy. METHODS: We included 12 patients
      of the 824 patients with ADHD using methylphenidate and atomoxetine combined
      therapy between the years 2010 and 2014. Kiddie-SADS, Turgay DSM-IV Based Child
      and Adolescent Behavior Disorders Screening and Rating Scale, Child Behavior
      Checklist, Clinic Global Impression Scale Severity and Impression (CGIS-S-I)
      scales were used. RESULTS: Patients were between the ages of 7 and 17 years.
      Before combined pharmacotherapy the CGIS-S score mean was 5.08. Mean CGIS-S score
      after the combined pharmacotherapy was 3.08 (P = 0.03; -2,980). The most common
      side effects were irritability (n = 5, 41.6%), appetite reduction (n = 3, 25%),
      palpitations (n = 2, 16.7%), headache (n = 1, 8.3%). CONCLUSIONS: Nine of these
      12 patients showed significant improvement in their symptoms, combined therapy
      enhanced the effectiveness of monotherapy.

PMID- 26223959
TI  - Delineating subtypes of self-injurious behavior maintained by automatic
      reinforcement.
AB  - Self-injurious behavior (SIB) is maintained by automatic reinforcement in roughly
      25% of cases. Automatically reinforced SIB typically has been considered a single
      functional category, and is less understood than socially reinforced SIB.
      Subtyping automatically reinforced SIB into functional categories has the
      potential to guide the development of more targeted interventions and increase
      our understanding of its biological underpinnings. The current study involved an
      analysis of 39 individuals with automatically reinforced SIB and a comparison
      group of 13 individuals with socially reinforced SIB. Automatically reinforced
      SIB was categorized into 3 subtypes based on patterns of responding in the
      functional analysis and the presence of self-restraint. These response features
      were selected as the basis for subtyping on the premise that they could reflect
      functional properties of SIB unique to each subtype. Analysis of treatment data
      revealed important differences across subtypes and provides preliminary support
      to warrant additional research on this proposed subtyping model. 

PMID- 26223960
TI  - Early fetal echocardiography: Experience of a tertiary diagnostic service.
AB  - BACKGROUND: There is a growing body of evidence that most of the major cardiac
      abnormalities can be diagnosed at 14-15 weeks of gestation. We present our
      experience of early fetal echocardiography. MATERIALS AND METHODS: This is a
      retrospective cohort study of women referred for early fetal echocardiography at
      13-16 weeks of gestation at Royal Prince Alfred Hospital and Sydney Ultrasound
      for Women between August 2011 and March 2014. Findings of early fetal
      echocardiography, details of subsequent ultrasound examinations and pregnancy
      outcome were recorded. RESULTS: Early fetal echocardiography was performed in 400
      euploid fetuses at a mean gestational age of 15(+2)  weeks. 85% of women were
      referred for increased nuchal translucency. 383/400 (96%) women had both normal
      early and late fetal echocardiograms 15/400 (3.7%) were found to have a cardiac
      defect at early fetal echocardiography, including 14 major and one minor
      abnormality. Two additional minor cardiac defects were diagnosed at later
      antenatal ultrasounds. One case, defined as being normal antenatally, was found
      to have a minor cardiac abnormality post-natally. Eight (57%) women whose fetus
      had a major cardiac defect chose to terminate the pregnancy. In the pregnancies
      that continued, the sensitivity and specificity for major cardiac defects was
      100%, 95% CI (0.98-1.00). CONCLUSION: Early fetal echocardiography is feasible
      and highly sensitive and specific in experienced hands. The high specificity
      facilitates early reassurance of those women assessed at increased risk for fetal
      cardiac malformations.

PMID- 26223961
TI  - Surveillance of waiting times for access to treatment: a registry-based computed
      approach in breast cancer care.
AB  - The current study set out to automatically generate waiting times for access to
      surgery, chemotherapy and radiotherapy, and to analyse their determinants for non
      metastatic breast cancer patients. We used data from the Poitou-Charentes
      regional cancer registry of women diagnosed with stages I-III breast carcinoma
      between 2008 and 2010. Waiting times were automatically computed from a
      previously validated algorithm modelling the care trajectory and then compared
      with national guidelines. The population of this study included 1082 patients.
      The compliance with guidelines ranged from 52.4% (access to adjuvant
      chemotherapy) to 89.2% (access to adjuvant radiotherapy). Younger age, a higher
      TNM stage, a lower grade, having a triple negative tumour, being the subject of
      multidisciplinary meetings and being a patient at a public hospital were
      associated with longer waiting times. The main result was the significant
      heterogeneity between geographical areas of treatment for all waiting times
      studied. The original, reproducible use of a registry-based automated algorithm
      to generate waiting times will help to follow these indicators routinely and
      efficiently. 

PMID- 26223962
TI  - Hybrid Organic-Inorganic Perovskites (HOIPs): Opportunities and Challenges.
AB  - The conclusions reached by a diverse group of scientists who attended an intense
      2-day workshop on hybrid organic-inorganic perovskites are presented, including
      their thoughts on the most burning fundamental and practical questions regarding
      this unique class of materials, and their suggestions on various approaches to
      resolve these issues. 

PMID- 26223963
TI  - Application of Minicircle Technology of Self-Reproducing Synthetic Protein Drugs
      in Preventing Skin Allograft Rejection.
AB  - BACKGROUND: Recently, it has been reported that minicircle vectors could allow
      the expression of transgenes using the protein synthesis system of the host.
      Here, we tested a novel strategy to permit the production of synthetic biologics
      using minicircle technology and evaluated their feasibility as a therapeutic tool
      in a skin allograft model. MATERIAL AND METHODS: We engineered vectors to carry
      cassette sequences for tocilizumab [anti-soluble interleukin-6 receptor (sIL-6R)
      antibody] and/or etanercept [tumor necrosis factor receptor 2 (TNFR2)-Fc fusion
      protein], and then isolated minicircle vectors from the parent vectors. We
      verified the production of proteins from minicircles and their duration in
      HEK293T cells and mice. We also evaluated whether these proteins were expressed
      at levels sufficient to ameliorate skin allograft rejection in mice. RESULTS:
      Each minicircle transfected into cells was detectable for at least 30 days. In
      mice, the drugs were mainly expressed in the liver and were detectable for at
      least 10 days after a single injection. These drugs were also detected in the
      blood. Treatment of mice with minicircles prolonged skin allograft survival,
      which was accompanied by a reduction of the number of interferon-gamma+ or
      interleukin-17+ lymphocytes and an induction of forkhead box P3 expression. These
      findings suggest that blocking of sIL-6R and/or TNF-alpha using minicircles
      encoding tocilizumab and/or etanercept was functionally active and relevant for
      preventing acute allograft rejection. CONCLUSIONS: Self-reproducing synthetic
      protein drugs produced using minicircle technology are potentially powerful tools
      for preventing acute rejection in transplantation.

PMID- 26223964
TI  - Acoustic Voice Analysis of Young Turkish Speakers.
AB  - OBJECTIVE/HYPOTHESIS: One of the objective assessments of voice is acoustic
      analysis, particularly, the parameters fundamental frequency (F0), jitter,
      shimmer, and noise-to-harmonics ratio (NHR). Because the normative data for
      healthy native Turkish male and female speakers are lacking in the literature,
      this study aimed to obtain F0, perturbation parameters, and NHR in three
      sustained vowels (/Lambda/, /i/, and /u/) among young Turkish speaking adults.
      METHODS: The native Turkish speakers with normal voice aged between 18 and 32
      years were included in the study (44 women, 39 men). Voice samples were recorded
      using Computerized Speech Lab, and data were analyzed with the statistics
      software SPSS Statistics 21.0 (IBM Corp., Armonk, NY, USA). RESULTS: The F0
      values of vowels /Lambda/, /i/, and /u/ were greater for women (239.78 Hz, 251.97
      Hz, and 250.29 Hz, respectively) than for men (127.11 Hz, 137.23 Hz, and 134.15
      Hz, respectively). All shimmer values for all vowels and jitter values for
      /Lambda/ and /u/ were found significantly low in men; however, no difference was
      found for jitter values of /i/ between genders. There is no effect of gender on
      NHR. Only in women, NHR of high vowels was found to be lower than that of vowel
      /Lambda/. CONCLUSIONS: There is a significant difference for F0 values between
      the genders as expected. Comparisons of perturbation values were significantly
      different for some pairs of vowels. There was no significant difference between
      NHR values between the genders. These findings can be compared with Turkish
      speakers who have different voice disorders for the further studies.

PMID- 26223965
TI  - Retraction.

PMID- 26223966
TI  - Bubble sorting in pinched microchannels for ultrasound contrast agent enrichment.
AB  - Ultrasound contrast agent (UCA) suspensions contain encapsulated microbubbles
      with a wide size distribution, with radii between 1 and 10 MUm. Medical
      transducers generally operate at a narrow frequency bandwidth, severely limiting
      the fraction of bubbles that resonates to the driving ultrasound. Thus, the
      sensitivity of contrast enhanced ultrasound imaging, molecular imaging with
      targeted bubbles, and drug delivery with microbubbles can be improved by
      narrowing down the size distribution of the bubble suspension. Here, we use a low
      cost lab-on-a-chip method for the sorting of microbubbles by their size without
      external actuation, based on a microfluidic separation technique known as pinched
      flow fractionation (PFF). We show by numerical investigation that the inclusion
      of particle rotation in the pinched segment is essential for an accurate
      description of the sorting behavior of particles with sizes close to the pinched
      segment width. Successful enrichment of a polydisperse contrast agent into a
      bubble suspension with a narrow size distribution (radius 1.56 +/- 0.30 MUm) was
      achieved with a PFF-based microdevice. This sorting technique can be readily
      parallelized, and may thus lead to an easy-to-use and robust device capable of
      enriching ultrasound contrast agents, leading to an improvement in the
      sensitivity of contrast ultrasound imaging. 

PMID- 26223967
TI  - The Specific Requirements for CR1 Retrotransposition Explain the Scarcity of
      Retrogenes in Birds.
AB  - Chicken repeat 1 (CR1) retroposons are the most abundant superfamily of
      transposable elements in the genomes of birds, crocodilians, and turtles.
      However, CR1 mobilization remains poorly understood. In this article, I document
      that the diverse CR1 lineages of land vertebrates share a highly conserved
      hairpin structure and an octamer microsatellite motif at their very 3' ends.
      Together with the presence of these same motifs in the tails of CR1-mobilized
      short interspersed elements, this suggests that the minimum requirement for CR1
      transcript recognition and retrotransposition is a complex >50-nt structure. Such
      a highly specific recognition sequence readily explains why CR1-dominated genomes
      generally contain very few retrogenes. Conversely, the mammalian richness in
      retrogenes results from CR1 extinction in their early evolution and subsequent
      establishment of L1 dominance. 

PMID- 26223968
TI  - Understanding the Stress Process of Chinese- and Korean-American Breast Cancer
      Survivors.
AB  - Guided by the stress process model (SPM), this study investigated the direct and
      indirect pathways of primary (negative self-image and life stress), secondary
      stressors (family communication strain) and family coping (external and internal)
      on mental health outcomes among Chinese- and Korean-American breast cancer
      survivors (BCS). A total of 156 Chinese- and Korean-American BCS were surveyed.
      Results showed primary and secondary stressors had a negative effect on better
      mental health outcomes. External coping was associated with better mental health.
      Family communication strain mediated the relationship between life stress and
      mental health outcomes. External coping mediated the relationship between family
      communication strain and mental health outcomes. Multi-group analysis revealed
      the stress process did not differ across ethnic groups. Findings suggest the SPM
      may be applicable to understand the stress process of Chinese- and Korean
      American BCS and provide valuable insight into the role of family communication
      and external coping on mental health outcomes.

PMID- 26223970
TI  - Spectroscopic and Crystal Field Consequences of Fluoride Binding by [Yb?DTMA](3+)
      in Aqueous Solution.
AB  - Yb?DTMA forms a ternary complex with fluoride in aqueous solution by displacement
      of a bound solvent molecule from the lanthanide ion. [Yb?DTMA?F](2+) and
      [Yb?DTMA?OH2 ](3+) are in slow exchange on the relevant NMR timescale (<2000 s(
      1) ), and profound differences are observed in their respective NMR and EPR
      spectra of these species. The observed differences can be explained by drastic
      modification of the ligand field states due to the fluoride binding. This changes
      the magnetic anisotropy of the Yb(III) ground state from easy-axis to easy-plane
      type, and this change is easily detected in the observed magnetic anisotropy
      despite thermal population of more than just the ground state. The spectroscopic
      consequences of such drastic changes to the ligand field represent important new
      opportunities in developing fluoride-responsive complexes and contrast agents. 

PMID- 26223969
TI  - MicroRNA-181a, a potential diagnosis marker, alleviates acute graft versus host
      disease by regulating IFN-gamma production.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a valuable
      therapeutic strategy for a wide variety of diseases. Acute graft-versus-host
      disease (aGVHD) is a major complication in up to 75% of allo-HSCT. The absence of
      a reliable predicative marker for aGVHD onset prevents preemptive treatment and
      impedes widespread and successful application of this therapy. In this study we
      found that after allo-HSCT, the levels of miR-181a were reduced significantly
      prior to the onset of aGVHD. More importantly, the degree of its reduction
      correlated with the severity of aGVHD. Mechanistically, miR-181a affects the
      function of T lymphocytes by down-regulating IFN-gamma in a dose-dependent
      manner. Meanwhile, we confirmed that miR-181a can effectively preserve the anti
      leukemic effect in vitro. Using a murine allo-HSCT model, we demonstrated that
      murine miR-181b, the human miR-181a homolog, served as an effective predictor of
      aGVHD. Moreover, expression of this microRNA ameliorated the severity of aGVHD.
      Collectively, these results show that the level of miR-181a may serve as a
      reliable marker for the diagnosis and prognosis the onset of aGVHD. Am. J.
      Hematol. 90:998-1007, 2015. (c) 2015 Wiley Periodicals, Inc. 

PMID- 26223972
TI  - Pankaj Sharma: Addicted to playing polo.

PMID- 26223971
TI  - Near-infrared spectroscopy as a tool for driving research.
AB  - Driving a motor vehicle requires various cognitive functions to process
      surrounding information, to guide appropriate actions, and especially to respond
      to or integrate with numerous contextual and perceptual hindrances or risks. It
      is, thus, imperative to examine driving performance and road safety from a
      perspective of cognitive neuroscience, which considers both the behaviour and the
      functioning of the brain. However, because of technical limitations of current
      brain imaging approaches, studies have primarily adopted driving games or
      simulators to present participants with simulated driving environments that may
      have less ecological validity. Near-infrared spectroscopy (NIRS) is a relatively
      new, non-invasive brain-imaging technique allowing measurement of brain
      activations in more realistic settings, even within real motor vehicles. This
      study reviews current NIRS driving research and explores NIRS' potential as a new
      tool to examine driving behaviour, along with various risk factors in natural
      situations, promoting our understanding about neural mechanisms of driving
      safety. Practitioner Summary: Driving a vehicle is dependent on a range of
      neurocognitive processing abilities. Near-infrared spectroscopy (NIRS) is a non
      invasive brain-imaging technique allowing measurement of brain activation even in
      on-road studies within real motor vehicles. This study reviews current NIRS
      driving research and explores the potential of NIRS as a new tool to examine
      driving behaviour. 

PMID- 26223973
TI  - A qualitative study of patient (dis)trust in public and private hospitals: the
      importance of choice and pragmatic acceptance for trust considerations in South
      Australia.
AB  - BACKGROUND: This paper explores the nature and reasoning for (dis)trust in
      Australian public and private hospitals. Patient trust increases uptake of,
      engagement with and optimal outcomes from healthcare services and is therefore
      central to health practice, policy and planning. METHODS: A qualitative study in
      South Australia, including 36 in-depth interviews (18 from public and 18 from
      private hospitals). RESULTS: 'Private patients' made active choices about both
      their hospital and doctor, playing the role of the 'consumer', where trust and
      choice went hand in hand. The reputation of the doctor and hospital were key
      drivers of trust, under the assumption that a better reputation equates with
      higher quality care. However, making a choice to trust a doctor led to personal
      responsibility and the additional requirement for self-trust. 'Public patients'
      described having no choice in their hospital or doctor. They recognised
      'problems' in the public healthcare system but accepted and even excused these as
      'part of the system'. In order to justify their trust, they argued that doctors
      in public hospitals tried to do their best in difficult circumstances, thereby
      deserving of trust. This 'resigned trust' may stem from a lack of alternatives
      for free health care and thus a dependence on the system. CONCLUSION: These two
      contrasting models of trust within the same locality point to the way different
      configurations of healthcare systems, hospital experiences, insurance coverage
      and related forms of 'choice' combine to shape different formats of trust, as
      patients act to manage their vulnerability within these contexts.

PMID- 26223974
TI  - MiRNA-149 modulates chemosensitivity of ovarian cancer A2780 cells to paclitaxel
      by targeting MyD88.
AB  - BACKGROUND: The low effectiveness of anticancer drugs remains a major unresolved
      obstacle to successful chemotherapy. Recently, much evidence on the roles of
      miRNAs in determining drug-sensitivity/resistance has been emerging. The
      relationship between miRNA-149 expression and paclitaxel chemoresistance in human
      ovarian cancer cells remains largely unknown. METHODS: This study investigated
      the relationship between miRNA-149 expression and the sensitivity of ovarian
      cancer A2780 cells to paclitaxel treatment. To achieve the down-regulation of
      miRNA-149 gene expression in A2780 cell line, the cells were infected with
      lentivirus carrying inhibitor of miRNA-149. Western blot and qRT-PCR were used to
      detect relevant protein levels and the expressions of mRNAs of interest. Cell
      proliferation was measured by CCK-8 assay. Flow cytometry was used to measure
      cell cycle and apoptosis. Transwell migration assay was used to observe the
      change of migration of transfected cells. RESULTS: Down-regulation of miRNA-149
      decreased the sensitivity of ovarian cancer A2780 cells to paclitaxel. After
      paclitaxel treatment, decreased apoptosis and G2 phase ratio, increased cell
      migration, increased level of Bcl-2, and decreased level of Bax were found in
      miRNA-149-down-regulated A2780 cells. MiRNA-149 down-regulation resulted in
      increased expression of MyD88 in A2780 cells. Down-regulation of miRNA-149 in
      A2780 cells increased MyD88 expression and decreased their sensitivity to
      paclitaxel treatment. CONCLUSION: Our findings suggest that miRNA-149 mediates
      the susceptibility of paclitaxel by regulating MyD88 expression in ovarian cancer
      cells.

PMID- 26223975
TI  - A cost-utility analysis of cervical cancer screening and human papillomavirus
      vaccination in the Philippines.
AB  - BACKGROUND: Cervical cancer is the second leading cause of cancer cases and
      deaths among Filipino women because of inadequate access to screening and
      treatment services. This study aims to evaluate the health and economic benefits
      of HPV vaccination and its combination with different screening strategies to
      find the most optimal preventive strategy in the Philippines. METHODS: A cost
      utility analysis was conducted using an existing semi-Markov model to evaluate
      different screening (i.e., Pap smear, visual inspection with acetic acid) and
      vaccination strategies against HPV infection implemented alone or as part of a
      combination strategy at different coverage scenarios. The model was run using
      country-specific epidemiologic, cost and clinical parameters from a health system
      perspective. Sensitivity analysis was performed for vaccine efficacy, duration of
      protection and costs of vaccination, screening and treatment. RESULTS: Across all
      coverage scenarios, VIA has been shown to be a dominant and cost-saving screening
      strategy with incremental cost-effectiveness ratio (ICER) ranging from dominant
      to Php 61,059 (1443 USD) per QALY gained. VIA can reduce cervical cancer cases
      and deaths by 25%. Pap smear screening was found to be not cost-effective due to
      its high cost in the Philippines. Adding HPV vaccination at a cost of 54 USD per
      vaccinated girl on top of VIA screening was found to be potentially cost
      effective using a threshold of 1 GDP per capita (i.e., Php 120,000 or 2835 USD/
      QALY) with the most favorable assumption of providing lifelong immunity against
      high-risk oncogenic HPV types 16/18. The highest incremental QALY gain was
      achieved with 80% coverage of the combined strategy of VIA at 35 to 45 years old
      done every five years following vaccination at 11 years of age with an ICER of
      Php 33,126 (783 USD). This strategy may result in a two-thirds reduction in
      cervical cancer burden. HPV vaccination is not cost-effective when vaccine
      protection lasts for less than 20 years. CONCLUSION: High VIA coverage targeting
      women aged 35-45 years old at five-year intervals is the most efficient and cost
      saving strategy in reducing cervical cancer burden in the Philippines. Adding a
      vaccination program at high coverage among 11-year-old girls is potentially cost
      effective in the Philippines assuming a life-long duration of vaccine efficacy.

PMID- 26223976
TI  - Factors affecting hospital readmission and rehospitalization following
      percutaneous nephrolithotomy.
AB  - PURPOSE: To identify patient- and procedure-related factors that increase the
      risk of hospital readmission and emergency room (ER) visits after percutaneous
      nephrolithotomy (PNL). MATERIALS AND METHODS: We retrospectively reviewed the
      records of patients with kidney stones treated via PNL in two tertiary referral
      hospitals between 2008 and 2014. Patient demographics including age, body mass
      indices, ASA score, stone size, presence of anatomic abnormality and comorbidity,
      operative and postoperative measures, and ER visit and rehospitalization rates
      were reviewed. Unplanned readmission to the hospital, including elective, and ER
      visits due to any reason related to the PNL procedure were primarily examined.
      The factors affecting ER visit and rehospitalization rate were analyzed using
      logistic regression analysis. RESULTS: A total of 1024 patients (mean age 46.57
      years) were enrolled into the study. Mean stone size was 28.5 mm. Stone-free
      status was achieved in 81.7 % of the procedures. Complications occurred at a rate
      of 6.44 % in the postoperative period. ER visit and rehospitalization rates were
      5.76 and 5.27 %, respectively. While stone complexity, anatomic abnormalities,
      and postoperative course were found to be factors affecting ER visit,
      postoperative course and hospitalization time were main predictors for
      rehospitalization rate. CONCLUSIONS: Our outcomes demonstrate that patients, who
      had an anatomic abnormality and complex kidney stone, were more likely to have an
      unplanned hospital readmission. Patients with a history of perioperative and/or
      postoperative complication seem to have a tendency to unplanned readmission and
      rehospitalization.

PMID- 26223977
TI  - Combined infectious bronchitis virus Arkansas and Massachusetts serotype
      vaccination suppresses replication of Arkansas vaccine virus.
AB  - Polyvalent infectious bronchitis virus vaccination is common worldwide. The
      possibility of vaccine interference after simultaneous combined vaccination with
      Arkansas (Ark) and Massachusetts (Mass)-type vaccines was evaluated in an effort
      to explain the high prevalence of Ark-type infectious bronchitis virus in
      vaccinated chickens. Chickens ocularly vaccinated with combinations of Ark and
      Mass showed predominance of Mass vaccine virus before 9 days post-vaccination
      (DPV) in tears. Even when Mass and Ark vaccines were inoculated into separate
      eyes, Mass vaccine virus was able to outcompete Ark vaccine virus. Although Mass
      vaccine virus apparently had a replication advantage over Ark vaccine in ocular
      tissues, Ark vaccine virus appeared to have an advantage in spreading to and/or
      replicating in the trachea. When chickens vaccinated with Ark or Mass vaccine
      were housed together, Mass vaccine virus was able to spread to Ark-vaccinated
      chickens, but the Ark vaccine was not detected in Mass-vaccinated chickens. Only
      Mass vaccine was detected in tears of sentinel birds introduced into groups
      receiving both vaccines. Furthermore, Ark vaccine virus RNA was not detectable
      until 10 DPV in most tear samples from chickens vaccinated with both Ark and Mass
      vaccines at varying Ark vaccine doses, while high concentrations of Mass virus
      RNA were detectable at 3-7 DPV. In contrast, Ark vaccine virus replicated
      effectively early after vaccination in chickens vaccinated with Ark vaccine
      alone. The different replication dynamics of Ark and Mass viruses in chickens
      vaccinated with combined vaccines did not result in reduced protection against
      Ark challenge at 21 DPV. Further studies are needed to clarify if the viral
      interference detected determines differences in protection against challenge at
      other time points after vaccination. 

PMID- 26223978
TI  - Effects of 24 weeks of Tai Chi Exercise on Postural Control among Elderly Women.
AB  - This study examined the effects of 24 weeks of Tai Chi Quan on the postural
      control of elderly women. A total of 43 women aged 55-68 years participated in
      the study. A Tai Chi group (n = 22) underwent an organized Tai Chi exercise,
      whereas the control group (n = 21) maintained a habitual, no-regular-exercise
      lifestyle. A Good Balance tester (Metitur, Finland) was used to measure the time,
      paths and velocity of the center of pressure (COP) of subjects during stance
      while shifting COP to targeted positions shown on a monitor. After 24 weeks, the
      Tai Chi group showed significantly shorter total (18.6%, p = 0.005), mediolateral
      (21.9%, p = 0.002) and anteroposterior (18.3%, p = 0.002) COP sway paths than the
      control group. The results indicate that 24 weeks of the Tai Chi exercise
      improved the efficiency of postural control for elderly women. 

PMID- 26223980
TI  - Synthesis of chiral hexacyclic steroids via [8pi + 2pi] cycloaddition of
      diazafulvenium methides.
AB  - First examples of [8pi + 2pi] cycloaddition of 16-dehydropregnenolone (16-DPA)
      acetate with diazafulvenium methides leading to chiral 4,5,6,7
      tetrahydropyrazolo[1,5-a]pyridine-fused steroids are reported. These hexacyclic
      steroids were obtained exclusively or selectively with the approach of the 1,7
      dipole by the less hindered alpha-face of 16-DPA. Quantum chemical calculations
      at the DFT level were carried out, using the cycloaddition of 1-methyl- and 1
      benzyl-diazafulvenium methides with N-phenylmaleimide as model reactions, in
      order to rationalize the stereochemistry outcome. The results indicate that endo
      cycloadditions of the more stable dipole conformation, having the 1-substituent
      pointing outward, are significantly more favorable than the alternative exo
      cycloaddition. 

PMID- 26223979
TI  - Production of mono- and sesquiterpenes in Camelina sativa oilseed.
AB  - MAIN CONCLUSION: Camelina was bioengineered to accumulate (4 S )-limonene and (+)
      delta-cadinene in seed. Plastidic localization of the recombinant enzymes
      resulted in higher yields than cytosolic localization. Overexpressing 1-deoxy- d 
      xylulose-5-phosphate synthase ( DXS ) further increased terpene accumulation.
      Many plant-derived compounds of high value for industrial or pharmaceutical
      applications originate from plant species that are not amenable to cultivation.
      Biotechnological production in low-input organisms is an attractive alternative.
      Several microbes are well established as biotechnological production platforms;
      however, their growth requires fermentation units, energy input, and nutrients.
      Plant-based production systems potentially allow the generation of high-value
      compounds on arable land with minimal input. Here we explore whether Camelina
      sativa (camelina), an emerging low-input non-foodstuff Brassicaceae oilseed crop
      grown on marginal lands or as a rotation crop on fallow land, can successfully be
      refactored to produce and store novel compounds in seed. As proof-of-concept, we
      use the cyclic monoterpene hydrocarbon (4S)-limonene and the bicyclic
      sesquiterpene hydrocarbon (+)-delta-cadinene, which have potential biofuel and
      industrial solvent applications. Post-translational translocation of the
      recombinant enzymes to the plastid with concurrent overexpression of 1-deoxy-D
      xylulose-5-phosphate synthase (DXS) resulted in the accumulation of (4S)-limonene
      and (+)-delta-cadinene up to 7 mg g(-1) seed and 5 mg g(-1) seed, respectively.
      This study presents the framework for rapid engineering of camelina oilseed
      production platforms for terpene-based high-value compounds.

PMID- 26223981
TI  - The CCR5Delta32 (rs333) polymorphism is not a predisposing factor for severe
      pandemic influenza in the Brazilian admixed population.
AB  - BACKGROUND: Recent studies have tried to identify host genetic variants that
      could explain severe cases and deaths in infection with Influenza A(H1N1)pdm09,
      especially among children and young adults. CCR5 is a chemokine receptor
      expressed on T cells, macrophages and dendritic cells, which is an important
      mediator of leukocyte chemotaxis during the immune response. A deletion mutation
      (Delta32) in this gene interferes with the response of immune cells, impairing
      viral clearance. We evaluated the CCR5Delta32 polymorphism (rs333) in individuals
      of the Brazilian admixed population with a diagnosis of Influenza A(H1N1)pdm09
      infection. METHODS: A total of 330 subjects with a diagnosis of Influenza
      A(H1N1)pdm09, evaluated at health services in the northern and northeastern
      regions of Brazil between June 2009 and August 2010, were genotyped for the
      Delta32 deletion (rs333). The cases were classified according to the progression
      of infection into a group of hospitalized patients (n = 156) and a group of non
      hospitalized patients (n = 174). RESULTS: No significant differences in the
      allele or genotype frequencies of the CCR5Delta32 polymorphism were observed
      between non-hospitalized and hospitalized patients (p = 0.289 and p = 0.431,
      respectively). CONCLUSION: The Delta32 deletion in the CCR5 gene is not
      associated with an unfavorable outcome in patients infected with Influenza
      A(H1N1)pdm09 in the Brazilian admixed population.

PMID- 26223983
TI  - A prospective evaluation of indications for neurological consultation in the
      emergency department.
AB  - BACKGROUND: Recognizing the diverse presentation of neurological conditions that
      emergency physicians encounter can be challenging, and management of these
      patients often requires consultation with a neurologist. Accurate diagnosis is
      critical in neurological emergencies because patient outcomes are often dependent
      on timely treatment. Our primary objective was to ascertain whether consultant
      neurologists understood the reason for consultation in the emergency department.
      METHODS: The authors conducted a prospective study of a non-consecutive sample of
      94 patients seen in an academic tertiary care emergency department (ED) who
      underwent consultation by neurologist over 4 consecutive months. At the time a
      consult was requested, we independently surveyed the treating ED physician for
      their differential diagnosis. Neurologists were also queried as to whether there
      was a clear indication for consultation. We then followed the patients to
      determine their final diagnosis and outcome. RESULTS: The median age was 57 years
      (interquartile range 45-78). 45.7 % were male. The clinical reasons for all the
      consults were 61 % focal symptom, 12 % concern about a specific diagnosis, 9 %
      radiological finding, 9 % diagnostic ambiguity, and 11 % other. There was no
      significant difference in the rate of a final neurological diagnosis based on the
      clinical reason for consult (p = 0.13). In the 17 % of patients for whom the
      treating neurologist reported a lack of a clear indication for the consultation,
      25 % were later admitted to a neurological service, and 69 % ultimately had a
      neurological diagnosis. CONCLUSIONS: Although patients with neurological
      emergencies can have diverse presentations, emergency physicians appear to
      utilize neurologic consultation appropriately. Additionally, nearly 70 % of
      patients for whom the consultant did not precisely understand the need for the
      consultation had neurological diagnoses. Time and resource constraints in the ED
      create challenges in making correct diagnosis.

PMID- 26223982
TI  - Kruppel-like factor 12 is a novel negative regulator of forkhead box O1
      expression: a potential role in impaired decidualization.
AB  - BACKGROUND: Decidualization is a prerequisite for successful implantation and the
      establishment of pregnancy. Kruppel-like factor 12 (KLF12) is a negative
      regulator of endometrial decidualization in vitro. We investigated whether KLF12
      was associated with impaired decidualization under conditions of repeated
      implantation failure (RIF). METHODS: Uterine tissues were collected from a mouse
      model of early pregnancy and artificial decidualization for immunohistochemistry,
      Western blot and real-time PCR analysis. Reporter gene assays, chromatin
      immunoprecipitation-PCR and avidin-biotin conjugate DNA precipitation assays were
      performed to analyze the transcriptional regulation of forkhead box O1 (FOXO1) by
      KLF12. Furthermore, the protein levels of KLF12 and FOXO1 in patients with RIF
      were analyzed by Western blot and immunohistochemistry. RESULTS: KLF12 led to
      defective implantation and decidualization in the mouse uterine model of early
      pregnancy and artificial decidualization by directly binding to the FOXO1
      promoter region and inhibiting its expression in human endometrial stromal cells.
      Elevated KLF12 expression was accompanied by decreased FOXO1 expression in the
      endometria of patients with RIF. CONCLUSIONS: As a novel regulator, KLF12
      predominantly controls uterine endometrial differentiation during early pregnancy
      and leads to implantation failure.

PMID- 26223984
TI  - What's in a name? Upper extremity fracture eponyms (Part 1).
AB  - Eponymous extremity fractures are commonly encountered in the emergency setting.
      Correct eponym usage allows rapid, succinct communication of complex injuries. We
      will review both common and less frequently encountered extremity fracture
      eponyms, focusing on imaging features to identify and differentiate these
      injuries. We focus on plain radiographic findings, with supporting computed
      tomography (CT) images. For each injury, important radiologic descriptors are
      discussed which may need to be communicated to consultants. Aspects of management
      and follow-up imaging recommendations are included. This is a two-part review:
      Part 1 focuses on fracture eponyms of the upper extremity, while Part 2 covers
      fracture eponyms of the lower extremity. 

PMID- 26223985
TI  - What's in a name? Lower extremity fracture eponyms (Part 2).
AB  - Eponymous extremity fractures are commonly encountered in the emergency setting.
      Correct eponym usage allows rapid, succinct communication of complex injuries. We
      review both common and less frequently encountered extremity fracture eponyms,
      focusing on imaging features to identify and differentiate these injuries. We
      focus on plain radiographic findings, with supporting computed tomography (CT)
      images. For each injury, important radiologic descriptors are discussed which may
      need to be communicated to clinicians. Aspects of management and follow-up
      imaging recommendations are included. This is a two-part review: Part 1 focuses
      on fracture eponyms of the upper extremity, while Part 2 encompasses fracture
      eponyms of the lower extremity. 

PMID- 26223986
TI  - Exercise stress echocardiography with tissue Doppler imaging in risk
      stratification of mild to moderate aortic stenosis.
AB  - BACKGROUND: Patients with mild to moderate aortic stenosis (AS) seem to have a
      worse outcome than commonly expected. Early identification of subjects who may
      develop a rapid disease progression or cardiovascular events is critical in order
      to apply adequate risk management. STUDY DESIGN: Observational prospective single
      centre study. OBJECTIVE: To determine the prognostic role of exercise stress
      echocardiography (ESE) in patients with mild and moderate asymptomatic AS.
      PATIENTS: Ninety consecutive patients (mean age 74 +/- 12 years) with isolated
      mild and moderate AS were enrolled into the study protocol over a 20 months
      period. Follow-up time was 12 months. METHODS: A complete echocardiographic study
      with tissue Doppler imaging (TDI) was performed at baseline and during semi
      supine symptom-limited exercise test to evaluate: (1) the occurrence of symptoms,
      (2) ST segment changes, (3) transaortic pressure gradient, (4) the E/A ratio, (5)
      the E/e' ratio and (6) the systolic pulmonary artery pressure. MAIN OUTCOME
      MEASURES: During the 1 year follow-up time, we evaluated the occurrence of
      adverse cardiac events, defined as any of the following: (1) cardio-vascular
      hospitalization; (2) requirement for aortic valve replacement; (3) cardiac death.
      RESULTS: During follow-up, three patients died, 11 underwent aortic valve
      replacement and 26 had cardiovascular hospitalizations. On univariate analysis,
      patients who exhibited symptoms during exercise (HR 2.93, p = 0.003); the
      occurrence of a >= 2 mm exercise-induced ST segment depression (HR 3.12, p =
      0.001); a >= 15 mmHg increase in mean transaortic pressure gradient during
      exercise (HR 2.77, p = 0.001); a >= 50 mmHg exercise-induced increase in systolic
      pulmonary artery pressure (HR 2.90, p = 0.009); an exercise-induced pseudo
      normalization of the E/A ratio (E/A >= 1) (HR 7.50, p = 0.0001) and,
      particularly, a >= 15 exercise-induced increase in the E/e' ratio (HR 7.69, p =
      0.0001) had a significantly higher risk of cardiac events during the follow-up
      time. On multivariate analysis, only the latter covariate (HR 6.04, p = 0.009)
      was independently associated with adverse cardiac events. CONCLUSIONS: A >= 15
      stress-induced increase in E/e' ratio is highly predictive of cardiac events in
      patients with mild to moderate AS. Assessment of diastolic function using TDI
      during ESE provides additional prognostic information in such patients.

PMID- 26223987
TI  - The accuracy of International Classification of Diseases coding for dental
      problems not associated with trauma in a hospital emergency department.
AB  - OBJECTIVES: Emergency department (ED) visits for nontraumatic dental conditions
      (NTDCs) may be a sign of unmet need for dental care. The objective of this study
      was to determine the accuracy of the International Classification of Diseases
      codes (ICD-10-CA) for ED visits for NTDC. METHODS: ED visits in 2008-2099 at one
      hospital in Toronto were identified if the discharge diagnosis in the
      administrative database system was an ICD-10-CA code for a NTDC (K00-K14). A
      random sample of 100 visits was selected, and the medical records for these
      visits were reviewed by a dentist. The description of the clinical signs and
      symptoms were evaluated, and a diagnosis was assigned. This diagnosis was
      compared with the diagnosis assigned by the physician and the code assigned to
      the visit. RESULTS: The 100 ED visits reviewed were associated with 16 different
      ICD-10-CA codes for NTDC. Only 2 percent of these visits were clearly caused by
      trauma. The code K0887 (toothache) was the most frequent diagnostic code (31
      percent). We found 43.3 percent disagreement on the discharge diagnosis reported
      by the physician, and 58.0 percent disagreement on the code in the administrative
      database assigned by the abstractor, compared with what it was suggested by the
      dentist reviewing the chart. CONCLUSION: There are substantial discrepancies
      between the ICD-10-CA diagnosis assigned in administrative databases and the
      diagnosis assigned by a dentist reviewing the chart retrospectively. However, ICD
      10-CA codes can be used to accurately identify ED visits for NTDC.

PMID- 26223988
TI  - Adhesion-induced instabilities and pattern formation in thin films of elastomers
      and gels.
AB  - A hydrostatically stressed soft elastic film circumvents the imposed constraint
      by undergoing a morphological instability, the wavelength of which is dictated by
      the minimization of the surface and the elastic strain energies of the film.
      While for a single film, the wavelength is entirely dependent on its thickness, a
      co-operative energy minimization dictates that the wavelength depends on both the
      elastic moduli and thicknesses of two contacting films. The wavelength can also
      depend on the material properties of a film if its surface tension has a
      pronounced effect in comparison to its elasticity. When such a confined film is
      subjected to a continually increasing normal displacement, the morphological
      patterns evolve into cracks, which, in turn, govern the adhesive fracture
      behavior of the interface. While, in general, the thickness provides the relevant
      length scale underlying the well-known Griffith-Kendall criterion of debonding of
      a rigid disc from a confined film, it is modified non-trivially by the elasto
      capillary number for an ultra-soft film. Depending upon the degree of confinement
      and the spatial distribution of external stress, various analogs of the canonical
      instability patterns in liquid systems can also be reproduced with thin confined
      elastic films. 

PMID- 26223989
TI  - Preoperative cytological diagnosis of malignant mesothelioma of tunica vaginalis.
AB  - Malignant mesothelioma of tunica vaginalis testis is a rare aggressive neoplasm
      with ~200 cases reported so far. A correct preoperative diagnosis of this rare
      tumor is difficult. Fine-needle aspiration cytology (FNAC) is a rapid and
      inexpensive diagnostic tool that may prove helpful in such cases. Very few cases
      have been diagnosed on cytology so far, and the descriptions of the cytological
      features have rarely been described in the literature. In this report we present
      the cytological features of malignant mesothelioma of tunica vaginalis testis
      which was diagnosed by FNAC and subsequently confirmed by histopatholoy and
      immunohistochemical (IHC) studies.

PMID- 26223990
TI  - Reply to Naucler and Berge.

PMID- 26223991
TI  - Editorial Commentary: This Little Piggy Went to Market-but Perhaps Should Have
      Stayed Home.

PMID- 26223992
TI  - Incidence and Patterns of Extended-Course Antibiotic Therapy in Patients
      Evaluated for Lyme Disease.
AB  - BACKGROUND: Most patients with Lyme disease (LD) can be treated effectively with
      2-4 weeks of antibiotics. The Infectious Disease Society of America guidelines do
      not currently recommend extended treatment even in patients with persistent
      symptoms. METHODS: To estimate the incidence of extended use of antibiotics in
      patients evaluated for LD, we retrospectively analyzed claims from a nationwide
      US health insurance plan in 14 high-prevalence states over 2 periods: 2004-2006
      and 2010-2012. RESULTS: As measured by payer claims, the incidence of extended
      antibiotic therapy among patients evaluated for LD was higher in 2010-2012 (14.72
      per 100 000 person-years; n = 684) than in 2004-2006 (9.94 per 100 000 person
      years; n = 394) (P < .001). Among these patients, 48.8% were treated with >=2
      antibiotics in 2010-2012 and 29.9% in 2004-2006 (P < .001). In each study period,
      a distinct small group of providers (roughly 3%-4%) made the diagnosis in >20% of
      the patients who were evaluated for LD and prescribed extended antibiotic
      treatment. CONCLUSIONS: Insurance claims data suggest that the use of extended
      courses of antibiotics and multiple antibiotics in the treatment of LD has
      increased in recent years.

PMID- 26223993
TI  - Long-Term Outcomes of Adding HPV Vaccine to the Anal Intraepithelial Neoplasia
      Treatment Regimen in HIV-Positive Men Who Have Sex With Men.
AB  - BACKGROUND: Recent evidence shows that quadrivalent human papillomavirus (qHPV)
      vaccination in men who have sex with men (MSM) who have a history of high-grade
      anal intraepithelial neoplasia (HGAIN) was associated with a 50% reduction in the
      risk of recurrent HGAIN. We evaluated the long-term clinical and economic
      outcomes of adding the qHPV vaccine to the treatment regimen for HGAIN in human
      immunodeficiency virus (HIV)-positive MSM aged >=27 years. METHODS: We
      constructed a Markov model based on anal histology in HIV-positive MSM comparing
      qHPV vaccination with no vaccination after treatment for HGAIN, the current
      practice. The model parameters, including baseline prevalence, disease
      transitions, costs, and utilities, were either obtained from the literature or
      calibrated using a natural history model of anal carcinogenesis. The model
      outputs included lifetime costs, quality-adjusted life years, and lifetime risk
      of developing anal cancer. We estimated the incremental cost-effectiveness ratio
      of qHPV vaccination compared to no qHPV vaccination and decrease in lifetime risk
      of anal cancer. We also conducted deterministic and probabilistic sensitivity
      analyses to evaluate the robustness of the results. RESULTS: Use of qHPV
      vaccination after treatment for HGAIN decreased the lifetime risk of anal cancer
      by 63% compared with no vaccination. The qHPV vaccination strategy was cost
      saving; it decreased lifetime costs by $419 and increased quality-adjusted life
      years by 0.16. Results were robust to the sensitivity analysis. CONCLUSIONS:
      Vaccinating HIV-positive MSM aged >=27 years with qHPV vaccine after treatment
      for HGAIN is a cost-saving strategy. Therefore, expansion of current vaccination
      guidelines to include this population should be a high priority.

PMID- 26223994
TI  - Live Animal Markets in Minnesota: A Potential Source for Emergence of Novel
      Influenza A Viruses and Interspecies Transmission.
AB  - BACKGROUND: Live animal markets have been implicated in transmission of influenza
      A viruses (IAVs) from animals to people. We sought to characterize IAVs at 2 live
      animal markets in Minnesota to assess potential routes of occupational exposure
      and risk for interspecies transmission. METHODS: We implemented surveillance for
      IAVs among employees, swine, and environment (air and surfaces) during a 12-week
      period (October 2012-January 2013) at 2 markets epidemiologically associated with
      persons with swine-origin IAV (variant) infections. Real-time reverse
      transcription polymerase chain reaction (rRT-PCR), viral culture, and whole
      genome sequencing were performed on respiratory and environmental specimens, and
      serology on sera from employees at beginning and end of surveillance. RESULTS:
      Nasal swabs from 11 of 17 (65%) employees tested positive for IAVs by rRT-PCR; 7
      employees tested positive on multiple occasions and 1 employee reported influenza
      like illness. Eleven of 15 (73%) employees had baseline hemagglutination
      inhibition antibody titers >=40 to swine-origin IAVs, but only 1 demonstrated a 4
      fold titer increase to both swine-origin and pandemic A/Mexico/4108/2009 IAVs.
      IAVs were isolated from swine (72/84), air (30/45), and pen railings (5/21).
      Whole-genome sequencing of 122 IAVs isolated from swine and environmental
      specimens revealed multiple strains and subtype codetections. Multiple gene
      segment exchanges among and within subtypes were observed, resulting in new
      genetic constellations and reassortant viruses. Genetic sequence similarities of
      99%-100% among IAVs of 1 market customer and swine indicated interspecies
      transmission. CONCLUSIONS: At markets where swine and persons are in close
      contact, swine-origin IAVs are prevalent and potentially provide conditions for
      novel IAV emergence.

PMID- 26223996
TI  - Editorial Commentary: The Mismatch Between Physicians' Expectations and
      Microbiologic Reality.

PMID- 26223995
TI  - Trends in Antibiotic Use and Nosocomial Pathogens in Hospitalized Veterans With
      Pneumonia at 128 Medical Centers, 2006-2010.
AB  - BACKGROUND: In 2005, pneumonia practice guidelines recommended broad-spectrum
      antibiotics for patients with risk factors for nosocomial pathogens. The impact
      of these recommendations on the ability of providers to match treatment with
      nosocomial pathogens is unknown. METHODS: Among hospitalizations with a principal
      diagnosis of pneumonia at 128 Department of Veterans Affairs medical centers from
      2006 through 2010, we measured annual trends in antibiotic selection; initial
      blood or respiratory cultures positive for methicillin-resistant Staphylococcus
      aureus (MRSA), Pseudomonas aeruginosa, and Acinetobacter species; and alignment
      between antibiotic coverage and culture results for MRSA and P. aeruginosa,
      calculating sensitivity, specificity, and diagnostic odds ratio using a 2 * 2
      contingency table. RESULTS: In 95 511 hospitalizations for pneumonia, initial use
      of vancomycin increased from 16% in 2006 to 31% in 2010, and piperacillin
      tazobactam increased from 16% to 27%, and there was a decrease in both
      ceftriaxone (from 39% to 33%) and azithromycin (change from 39% to 36%) (P < .001
      for all). The proportion of hospitalizations with cultures positive for MRSA
      decreased (from 2.5% to 2.0%; P < .001); no change was seen for P. aeruginosa
      (1.9% to 2.0%; P = .14) or Acinetobacter spp. (0.2% to 0.2%; P = .17). For both
      MRSA and P. aeruginosa, sensitivity increased (from 46% to 65% and 54% to 63%,
      respectively; P < .001) and specificity decreased (from 85% to 69% and 76% to
      68%; P < .001), with no significant changes in diagnostic odds ratio (decreases
      from 4.6 to 4.1 [P = .57] and 3.7 to 3.2 [P = .95], respectively). CONCLUSIONS:
      Between 2006 and 2010, we found a substantial increase in the use of broad
      spectrum antibiotics for pneumonia despite no increase in nosocomial pathogens.
      The ability of providers to accurately match antibiotic coverage to nosocomial
      pathogens remains low.

PMID- 26223997
TI  - High Risk Features Contrast With Favorable Outcomes in HIV-associated Hodgkin
      Lymphoma in the Modern cART Era, ANRS CO16 LYMPHOVIR Cohort.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with a
      high risk of classical Hodgkin's lymphoma (cHL) in the combined antiretroviral
      therapy (cART) era. METHODS: We analyzed the characteristics and outcome of HIV
      associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir
      cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with
      cHL. HIV-HL patients were compared with a series of non-HV-infected patients
      consecutively diagnosed with HL. RESULTS: Most patients (76%) had Ann-Arbor
      stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median
      CD4 T-cell count was 387/uL and 94% of patients were treated with cART. All
      patients received cART after diagnosis. Five patients died from early progression
      (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during
      follow-up. Two-year overall and progression free survivals (PFS) were 94% [95%
      CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with
      progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45
      years. The PFS of Lymphovir patients appeared similar to PFS of HIV-negative
      patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk
      features than HIV-negative patients. CONCLUSIONS: Although high-risk features
      still predominate in HIV-HL, the prognosis of these patients, treated with cART
      and mainly ABVD, has markedly improved in the modern cART era and is now similar
      to non-HIV-infected patients.

PMID- 26223998
TI  - Reply to Tien et al.

PMID- 26223999
TI  - Screening Algorithm to Perform Transesophageal Echocardiography in Patients With
      Staphylococcus aureus Bacteremia.

PMID- 26224000
TI  - Tolerability of Fluoroquinolones in Management of Latent Tuberculosis in Liver
      Transplant Candidates.

PMID- 26224001
TI  - Immunization costs and programmatic barriers at an urban HIV clinic.
AB  - BACKGROUND: Although the increasing number of recommended immunizations is
      essential for patients infected with human immunodeficiency virus (HIV), the
      potentially uncompensated costs of expanded immunizations will present
      significant challenges for clinics and health systems serving HIV-infected
      patients. METHODS: We estimated costs of providing Gardasil, Prevnar, and
      Zostavax to eligible patients at a US Ryan White Part C academically affiliated
      HIV clinic in 2013. Clinic expenditures were calculated using vaccine price and
      administrative fees. Revenue was calculated using insurance reimbursement data
      for vaccination and administration. Three scenarios were used: 100% uptake of
      vaccines, adjusted uptake based on published rates, and adjusted reimbursement
      according to pre-Affordable Care Act (ACA) insurance status. RESULTS: 2887
      patients (27% Medicare, 13% Alabama Medicaid, 26% Commercial, 34% Uninsured),
      received care with wide variation in immunization reimbursement ($0 to $210) by
      insurance and vaccine. The net yield (revenue minus expenditure) was calculated
      for each vaccine. Prevnar was most costly: annual net yield of -$60 691.
      Provision of all 3 vaccines would lead to a net yield of -$97 122. Adjusting for
      reduced uptake led to annual clinic losses of $44 119. Using pre-ACA
      reimbursement for immunization of the uninsured led to reduced clinic losses (
      $62 326), attributable to reimbursement via Ryan White funds. CONCLUSIONS: A cost
      analysis of 3 vaccines shows great variation in insurance coverage, with
      potential losses of almost $100 000 for one HIV clinic if eligible patients
      received vaccinations in one calendar year. Adequate, cost neutral reimbursement
      should be instituted if medical providers and health systems are to achieve
      Advisory Committee on Immunization Practices immunization recommendations for
      both HIV positive and negative adults.

PMID- 26224002
TI  - Create Allies, IDSA Stewardship Commitments Should Prioritize Health Professions
      Learners.

PMID- 26224003
TI  - 5Alpha-Reduced Steroids Are Major Metabolites in the Early Equine Embryo Proper
      and Its Membranes.
AB  - Steroid production and metabolism by early conceptuses are very important for the
      establishment and maintenance of pregnancy in horses. Our earlier work suggested
      the possible formation of 5alpha-reduced steroids in equine conceptuses. We have
      now demonstrated the formation of 5alpha-reduced metabolites of androstenedione,
      testosterone, and progesterone by the embryo and its membranes. A total of 44
      conceptuses were collected from 26 mares between 20 and 31 days of pregnancy.
      Tissues from the embryo proper and from the separated components of the conceptus
      (bilaminar and trilaminar trophoblast, allantois) were incubated with tritium
      labeled substrates. 5Alpha-reduced metabolites (5alpha-dihydro- and 3beta,5alpha
      tetrahydro- steroids) as radiolabeled products were identified from a series of
      chromatographic steps using four solvent systems for high-performance liquid
      chromatography. Use of a 5alpha-reductase inhibitor confirmed the metabolites
      were indeed 5alpha-reduced steroids. For the embryo, the only products from
      androstenedione were 5alpha-dihydroandrostenedione and 3beta,5alpha
      tetrahydroandrostenedione, with no evidence of more polar metabolites; there was
      some 3beta,5alpha-tetrahydrotestosterone but no 5alpha-dihydrotestosterone from
      testosterone, and formation of androstenedione was followed by the production of
      5alpha-dihydroandrostenedione and 3beta,5alpha-tetrahydroandrostenedione. The
      major 5alpha-reduced product from progesterone was 3beta,5alpha
      tetrahydroprogesterone, with lesser amounts of 5alpha-dihydroprogesterone. For
      the membranes, reductions to tetrahydro, 5alpha-reduced steroids were prominent
      in most instances, but also present were considerable amounts of products more
      polar than the substrates. The well-recognized activity of some 5alpha-reduced
      steroids--for example, 5alpha-dihydrotestosterone in male sexual differentiation-
      provokes interest in their even earlier appearance, as seen in this study, and
      suggests a possible role for them in early embryonic development in horses and,
      more generally, in other species.

PMID- 26224005
TI  - Left-Biased Spermatogenic Failure in 129/SvJ Dnd1Ter/+ Mice Correlates with
      Differences in Vascular Architecture, Oxygen Availability, and Metabolites.
AB  - Homozygosity for the Ter mutation in the RNA-binding protein Dead end 1
      (Dnd1(Ter/Ter)) sensitizes germ cells to degeneration in all mouse strains. In
      129/SvJ mice, approximately 10% of Dnd1(Ter/+) heterozygotes develop
      spermatogenic failure, and 95% of unilateral cases occur in the left testis. The
      first differences between right and left testes were detected at Postnatal Day 15
      when many more spermatogonial stem cells (SSCs) were undergoing apoptosis in the
      left testis compared to the right. As we detected no significant left/right
      differences in the molecular pathway associated with body axis asymmetry or in
      the expression of signals known to promote proliferation, differentiation, and
      survival of germ cells, we investigated whether physiological differences might
      account for asymmetry of the degeneration phenotype. We show that left/right
      differences in vascular architecture are associated with a decrease in hemoglobin
      saturation and increased levels of HIF-1alpha in the left testis compared to the
      right. In Dnd1 heterozygotes, lower oxygen availability was associated with
      metabolic differences, including lower levels of ATP and NADH in the left testis.
      These experiments suggest a dependence on oxygen availability and metabolic
      substrates for SSC survival and suggest that Dnd1(Ter/+) SSCs may act as
      efficient sensors to detect subtle environmental changes that alter SSC fate. 

PMID- 26224004
TI  - BRCA Mutations, DNA Repair Deficiency, and Ovarian Aging.
AB  - Oocyte aging has a significant impact on reproductive outcomes both
      quantitatively and qualitatively. However, the molecular mechanisms underlying
      the age-related decline in reproductive success have not been fully addressed.
      BRCA is known to be involved in homologous DNA recombination and plays an
      essential role in double-strand DNA break repair. Given the growing body of
      laboratory and clinical evidence, we performed a systematic review on the current
      understanding of the role of DNA repair in human reproduction. We find that BRCA
      mutations negatively affect ovarian reserve based on convincing evidence from in
      vitro and in vivo results and prospective studies. Because decline in the
      function of the intact gene occurs at an earlier age, women with BRCA1 mutations
      exhibit accelerated ovarian aging, unlike those with BRCA2 mutations. However,
      because of the still robust function of the intact allele in younger women and
      because of the masking of most severe cases by prophylactic oophorectomy or
      cancer, it is less likely one would see an effect of BRCA mutations on fertility
      until later in reproductive age. The impact of BRCA2 mutations on reproductive
      function may be less visible because of the delayed decline in the function of
      normal BRCA2 allele. BRCA1 function and ataxia-telangiectasia-mutated (ATM)
      mediated DNA repair may also be important in the pathogenesis of age-induced
      increase in aneuploidy. BRCA1 is required for meiotic spindle assembly, and
      cohesion function between sister chromatids is also regulated by ATM family
      member proteins. Taken together, these findings strongly suggest the implication
      of BRCA and DNA repair malfunction in ovarian aging. 

PMID- 26224007
TI  - Unstable Foxp3+ regulatory T cells and altered dendritic cells are associated
      with lipopolysaccharide-induced fetal loss in pregnant interleukin 10-deficient
      mice.
AB  - Maternal interleukin (IL) 10 deficiency elevates susceptibility to fetal loss
      induced by the model Toll-like receptor agonist lipopolysaccharide, but the
      mechanisms are not well elucidated. Here, we show that Il10 null mutant (Il10(-/
      )) mice exhibit altered local T cell responses in pregnancy, exhibiting
      pronounced hyperplasia in para-aortic lymph nodes draining the uterus with >6
      fold increased CD4(+) and CD8(+) T cells compared with wild-type controls. Among
      these CD4(+) cells, Foxp3(+) T regulatory (Treg) cells were substantially
      enriched, with 11-fold higher numbers at Day 9.5 postcoitum. Lymph node
      hypertrophy in Il10(-/-) mice was associated with more activated phenotypes in
      dendritic cells and macrophages, with elevated expression of MHCII, scavenger
      receptor, and CD80. Affymetrix microarray revealed an altered transcriptional
      profile in Treg cells from pregnant Il10(-/-) mice, with elevated expression of
      Ctse (cathepsin E), Il1r1, Il12rb2, and Ifng. In vitro, Il10(-/-) Treg cells
      showed reduced steady-state Foxp3 expression, and polyclonal stimulation caused
      greater loss of Foxp3 and reduced capacity to suppress IL17 in CD4(+)Foxp3(-) T
      cells. We conclude that despite a substantially expanded Treg cell pool, the
      diminished stability of Treg cells, increased numbers of effector T cells, and
      altered phenotypes in dendritic cells and macrophages in pregnancy all
      potentially confer vulnerability to inflammation-induced fetal loss in Il10(-/-)
      mice. These findings suggest that IL10 has a pivotal role in facilitating robust
      immune protection of the fetus from inflammatory challenge and that IL10
      deficiency could contribute to human gestational disorders in which altered T
      cell responses are implicated. 

PMID- 26224006
TI  - Male Rat Germ Cells Display Age-Dependent and Cell-Specific Susceptibility in
      Response to Oxidative Stress Challenges.
AB  - For decades male germ cells were considered unaffected by aging, due to the fact
      that males continue to generate sperm into old age; however, evidence indicates
      that germ cells from aged males are of lower quality than those of young males.
      The current study examines the effects of aging on pachytene spermatocytes and
      round spermatids, and is the first study to culture these cells in isolation for
      an extended period. Our objective is to determine the cell-specific responses
      germ cells have to aging and oxidative insult. Culturing isolated germ cells from
      young and aged Brown Norway rats revealed that germ cells from aged males
      displayed an earlier decline in viability, elevated levels of reactive oxygen
      species (ROS), and increased spermatocyte DNA damage, compared to young males.
      Furthermore, oxidative insult by prooxidant 3-morpholinosydnonimine provides
      insight into how spermatocytes and spermatids manage excess ROS. Genome-wide
      microarray analyses revealed that several transcripts for antioxidants, Sod1,
      Cat, and Prdxs, were up-regulated in response to ROS in germ cells from young
      males while being expressed at lower levels in the aged. In contrast, the
      expression of DNA damage repair genes Rad50 and Atm were increased in the germ
      cells from aged animals. Our data indicate that as germ cells undergo
      spermatogenesis, they adapt and respond to oxidative stress differently,
      depending on their phase of development, and the process of aging results in
      redox dysfunction. Thus, even at early stages of spermatogenesis, germ cells from
      aged males are unable to mount an appropriate response to manage oxidative
      stress. 

PMID- 26224008
TI  - Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat
      Adult Offspring.
AB  - Previous studies have demonstrated that perinatal nicotine exposure increased
      blood pressure (BP) in adult offspring. However, the underlying mechanisms were
      unclear. The present study tested the hypothesis that perinatal nicotine-induced
      programming of hypertensive response is mediated by enhanced reactive oxygen
      species (ROS) in the vasculature. Nicotine was administered to pregnant rats via
      subcutaneous osmotic mini-pumps from Day 4 of gestation to Day 10 after birth, in
      the absence or presence of the ROS inhibitor N-acetyl-cysteine (NAC) in the
      drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal
      nicotine treatment resulted in a significant increase in arterial ROS production
      in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP
      responses were significantly higher in nicotine-treated group than in saline
      treated control group, and NAC treatment blocked the nicotine-induced increase in
      BP response. Consistent with that, the nicotine treatment significantly increased
      both Ang II-induced and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)
      induced arterial contractions in adult offspring, which were blocked by NAC
      treatment. In addition, perinatal nicotine treatment significantly attenuated
      acetylcholine-induced arterial relaxation in offspring, which was also inhibited
      by NAC treatment. Results demonstrate that inhibition of ROS blocks the nicotine
      induced increase in arterial reactivity and BP response to vasoconstrictors in
      adult offspring, suggesting a key role for increased oxidative stress in nicotine
      induced developmental programming of hypertensive phenotype in male offspring. 

PMID- 26224009
TI  - Effects of synchronous and asynchronous embryo transfer on postnatal development,
      adult health, and behavior in mice.
AB  - Asynchronous embryo transfer (ET) is a common assisted reproduction technique
      used in several species, but its biological effects on postnatal and early
      development remain unknown. The aim of this study was to determine whether
      asynchronous ET produces long-term effects in mice. Postnatal development, animal
      weight, systolic blood pressure (SBP), relative organ weight (liver, spleen,
      kidneys, heart, lungs, brain, and testicles), and behavior (assessed in open
      field and elevated plus maze tests) were assessed in CD1 mice produced by
      different ET procedures: 1) the transfer of Day 3.5 (D3.5) blastocysts to the
      uterus (BL-UT); 2) the transfer of D3.5 blastocysts to the oviduct (BL-OV); or 3)
      the transfer of D0.5 zygotes to the oviduct (Z-OV). In vivo conceived animals
      served as controls (CT). The transfer of blastocysts to the uterus or zygotes to
      the oviduct was defined as synchronous, and transfer of blastocysts to the
      oviduct was defined as asynchronous. Both synchronous and asynchronous ET
      resulted in increased weight at birth that normalized thereafter with the
      exception of asynchronous ET females. In this group, female BL-OV, a clear lower
      body weight was recorded along postnatal life when compared with controls (P <
      0.05). No effects on animal weight were produced during postnatal development in
      the synchronous ET groups (BL-UT, Z-OV, and CT). Both synchronous and
      asynchronous ET had impacts on adult (Wk 30) organ weight. SBP was modified in
      animals derived from blastocyst but not zygote ET. Effects on behavior (anxiety
      in the plus maze) were only detected in the BL-UT group (P < 0.05). Our findings
      indicate that zygotes are less sensitive than blastocysts to ET and that both
      synchronous and asynchronous blastocyst ET may have long-term consequences on
      health, with possible impacts on weight, arterial pressure, relative organ
      weight, and behavior. 

PMID- 26224010
TI  - Molecular characterization of ring chromosome 18 by low-coverage next generation
      sequencing.
AB  - BACKGROUND: Ring chromosomes are one category of structurally abnormal
      chromosomes that can lead to severe growth retardation and other clinical
      defects. Traditionally, their diagnosis and characterization has largely relied
      on conventional cytogenetics and fluorescence in situ hybridization, array-based
      comparative genomic hybridization and single nucleotide polymorphism array-based
      comparative genomic hybridization. However, these methods are ineffectively at
      characterizing the ring chromosome structure and only offer a low resolution
      mapping of breakpoints. Here, we applied whole-genome low-coverage paired-end
      next generation sequencing (NGS) to two suspected cases of ring chromosome 18
      (r(18)) and characterized the ring structure including the chromosome dosage
      changes and the breakpoint junction. METHODS: The breakpoints and chromosome copy
      number variations (CNVs) of r(18) were characterized by whole-genome low-coverage
      paired-end NGS. We confirmed the dosage change by single nucleotide polymorphisms
      array, and validated the junction site regions using PCR followed by Sanger
      sequencing. RESULTS: We successfully and fully characterized the r(18) in two
      cases by NGS. We mapped the breakpoints with a high resolution and identified all
      CNVs in both cases. We analyzed the breakpoint regions and discovered two
      breakpoints located within repetitive sequence regions, and two near the
      repetitive sequence regions. One of the breakpoints in case 2 was located within
      the gene METTL4, while the other breakpoints were intergenic. CONCLUSIONS: We
      demonstrated that whole-genome low-coverage paired-end NGS can be used directly
      to map breakpoints with a high molecular resolution and detect all CNVs on r(18).
      This approach will provide new insights into the genotype-phenotype correlations
      on r(18) and the underlying mechanism of ring chromosomes formation. Our results
      also demonstrate that this can be a powerful approach for the diagnosis and
      characterization of ring chromosomes in the clinic.

PMID- 26224011
TI  - 12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell
      Proliferation via PKC Activation.
AB  - BACKGROUND: Neuropsychiatric and neurological disorders frequently occur after
      brain insults associated with neuronal loss. Strategies aimed to facilitate
      neuronal renewal by promoting neurogenesis constitute a promising therapeutic
      option to treat neuronal death-associated disorders. In the adult brain,
      generation of new neurons occurs physiologically throughout the entire life
      controlled by extracellular molecules coupled to intracellular signaling
      cascades. Proteins participating in these cascades within neurogenic regions
      constitute potential pharmacological targets to promote neuronal regeneration of
      injured areas of the central nervous system. METHODOLOGY: We have performed in
      vitro and in vivo approaches to determine neural progenitor cell proliferation to
      understand whether activation of kinases of the protein kinase C family
      facilitates neurogenesis in the adult brain. RESULTS: We have demonstrated that
      protein kinase C activation by phorbol-12-myristate-13-acetate induces neural
      progenitor cell proliferation in vitro. We also show that the nontumorogenic
      protein kinase C activator prostratin exerts a proliferative effect on neural
      progenitor cells in vitro. This effect can be reverted by addition of the protein
      kinase C inhibitor G06850, demonstrating that the effect of prostratin is
      mediated by protein kinase C activation. Additionally, we show that prostratin
      treatment in vivo induces proliferation of neural progenitor cells within the
      dentate gyrus of the hippocampus and the subventricular zone. Finally, we
      describe a library of diterpenes with a 12-deoxyphorbol structure similar to that
      of prostratin that induces a stronger effect than prostratin on neural progenitor
      cell proliferation both in vitro and in vivo. CONCLUSIONS: This work suggests
      that protein kinase C activation is a promising strategy to expand the endogenous
      neural progenitor cell population to promote neurogenesis and highlights the
      potential of 12-deoxyphorbols as pharmaceutical agents to facilitate neuronal
      renewal.

PMID- 26224012
TI  - Why item response theory should be used for longitudinal questionnaire data
      analysis in medical research.
AB  - BACKGROUND: Multi-item questionnaires are important instruments for monitoring
      health in epidemiological longitudinal studies. Mostly sum-scores are used as a
      summary measure for these multi-item questionnaires. The objective of this study
      was to show the negative impact of using sum-score based longitudinal data
      analysis instead of Item Response Theory (IRT)-based plausible values. METHODS:
      In a simulation study (varying the number of items, sample size, and distribution
      of the outcomes) the parameter estimates resulting from both modeling techniques
      were compared to the true values. Next, the models were applied to an example
      dataset from the Amsterdam Growth and Health Longitudinal Study (AGHLS). RESULTS:
      The results show that using sum-scores leads to overestimation of the within
      person (repeated measurement) variance and underestimation of the between person
      variance. CONCLUSIONS: We recommend using IRT-based plausible value techniques
      for analyzing repeatedly measured multi-item questionnaire data.

PMID- 26224013
TI  - Long-term follow-up of late onset vestibular complaints in patients with cochlear
      implant.
AB  - CONCLUSION: Patients with cochlear implants should be treated no differently than
      non-implanted patients with similar symptomatology. OBJECTIVES: To describe the
      spectrum of symptomatology, treatment, and long-term follow-up of patients with
      cochlear implant and vestibular complaints. METHODS: This retrospective study
      included 25 patients with late onset vestibular complaints (more than 1 month
      post-implantation). Each patient underwent an extensive interrogatory and
      physical exam with ancillary test to complete a diagnosis. Treatment was given
      according to this and all patients followed a vestibular rehabilitation program.
      RESULTS: The total population was 72% male and 28% female, median age was 58
      years; minimal follow-up was 9 months (mean = 51, median = 34). Cochleostomy was
      performed in eight cases and round window insertion was performed in 19 (two
      patients were removed from each group in the analysis due to their bilateral
      implantation under a different approach). The mean time from implant to
      vestibular symptoms was 53 months, median = 32; a Kaplan Meier graphic showed the
      round window approach has faster onset of symptoms with statistical significance
      (p = 0.020). The most common complaint was instability in all patients and after
      both surgical approaches. No difference in symptoms was found with a Kruskall
      Wallis test except for vertigo spells (more common in the round window approach).
      In 12 patients the symptomatology was attributed to the implanted side. In the
      long-term follow-up a relatively high number of patients (20/25) recovered with
      standard treatment, suggesting the presence of the implant is not associated with
      poor recovery prognosis.

PMID- 26224014
TI  - Joint associations of smoking and physical activity with disability retirement: a
      register-linked cohort study.
AB  - OBJECTIVES: We examined the risk of disability retirement by smoking and physical
      activity, and particularly whether the risk due to smoking is affected by the
      level of physical activity. Additionally, the contribution of baseline health,
      sociodemographic and work-related factors to the joint associations of smoking
      and physical activity with disability retirement was considered. DESIGN: Cohort
      study. SETTING: Helsinki, Finland. PARTICIPANTS: Employees of the City of
      Helsinki, aged 40-60 years at baseline in 2000-2002, were followed up using
      complete register data from the Finnish Centre of Pensions until the end of 2010
      (n=6390, with a consent to register linkage from 74%). PRIMARY OUTCOME MEASURE:
      All-cause disability retirement (ICD-10). RESULTS: Altogether, 608 employees
      (9.5%) retired due to disability during the follow-up. Cox regression models were
      fitted to examine the joint associations of smoking and physical activity with
      subsequent disability retirement. Never-smokers, ex-smokers and moderate smokers
      who were inactive or moderately active had an increased risk of disability
      retirement, but if they were vigorously active, they had no excess risk. Instead,
      all heavy smokers (15 or more cigarettes per day among women, and 20 or more
      among men), irrespective of physical activity, had an increased risk of
      disability retirement. The examined associations attenuated but remained for ex
      smokers and heavy smokers after adjustments for gender, age, socioeconomic
      position, mental and physical workload, problem drinking, body mass index and
      self-rated health. No gender interactions were found. CONCLUSIONS: Vigorous
      physical activity might help prevent disability retirement not only among never
      smokers, but even among ex-smokers and moderate smokers. However, among heavy
      smokers, physical activity is not sufficient to eliminate the adverse effects of
      smoking on health and work ability.

PMID- 26224015
TI  - Perinatal consequences of a category 1 caesarean section at term.
AB  - OBJECTIVE: To characterise maternal demographics, obstetric risk factors and
      neonatal outcomes associated with term category 1 caesarean sections (CS). DESIGN
      AND SETTING AND MAIN OUTCOME MEASURES: Retrospective study of term singleton
      pregnancies delivering at a major tertiary unit in Brisbane, Australia. Category
      1 CS were defined as one that required a decision-to-delivery time interval of
      <30 min when there was an immediate threat to the life of a woman or fetus.
      Neonatal outcomes analysed were gestation at delivery, birth weight, Apgar
      scores, acidosis at birth, need for resuscitation, admission to neonatal
      intensive care and neonatal seizures and death. RESULTS: A total of 30,719 women
      delivering at term were included. Of these, 1179 (3.8%) women required a category
      1 CS. A further 3527 women underwent non-category 1 CS. Most category 1 CS were
      performed for non-reassuring fetal status (65.9%, 777/1179). The indications for
      non-category 1 CS were for failure to progress (46.5%, 1641/3527) and non
      reassuring fetal status (19%, 671/3527). Maternal age, body mass index and
      medical disease did not differ significantly between the two cohorts. Caucasian
      women were equally as likely to undergo a category 1 CS as a non-category 1 CS,
      while indigenous women and women of Asian ethnicity were more likely to undergo a
      category 1 CS. Significantly higher (p<0.001) perinatal complications were seen
      in the category 1 CS cohort--Apgar scores <7 at 1 min (20.4%, 241/1179 vs 10.7%,
      377/3527) and 5 min (5.8%, 68/1179 vs 1.9%, 67/3527), umbilical arterial pH<7.2
      (23.7%, 279/1179 vs 9.1%, 321/3527), neonatal resuscitation (59.9%, 706/1179 vs
      51.8%, 1828/3527), neonatal intensive care unit admission (9.8%, 116/1179 vs
      2.5%, 87/3527) and seizures (0.8%, 10/1179 vs 0.3%, 9/3527), respectively.
      CONCLUSIONS: These results demonstrate significantly poorer outcomes associated
      with term category 1 CS compared with non-category 1 emergency CS.

PMID- 26224016
TI  - Proposal for an annual skin examination by a general practitioner for patients at
      high risk for melanoma: a French cohort study.
AB  - OBJECTIVE: To evaluate the efficacy of a targeted screening for melanoma in high
      risk patients following the receipt of a mailed invitation to an annual skin
      examination by a general practitioner (GP). METHODS: A prospective cohort study
      was conducted in a primary care setting in western France. A total of 3897
      patients at elevated risk of melanoma (identified using the Self-Assessment of
      Melanoma Risk Score) consented to participate in a targeted melanoma screening
      project in 2011. One year later, the participants were invited by mail to consult
      their GP for an annual skin examination. Efficacy of the procedure was evaluated
      according to patient participation and the number of melanomas detected. The
      consultation dates and results were collected during the 12 months postreminder
      and were analysed using SAS. Analyses of whether participation decreased compared
      with that during the year of inclusion and whether populations at risk for thick
      melanoma showed reduced participation in the screening were performed. RESULTS:
      Of the 3745 patients who received the mailed invitation, 61% underwent a skin
      examination. The participation of patients at risk for thick melanoma (any
      patient over 60 years of age and men over 50 years of age) was significantly
      greater than that of the patients in the other subgroups (72.4% vs 49.6%,
      p<0.001; and 66% vs 52.4%, p<0.001, respectively). The patients referred to the
      dermatologist after 1 year were more compliant compared with those referred
      during the first year (68.8% vs 59.1%, p=0.003). Six melanomas were detected
      within 1 year postreminder; therefore, the incidence of melanoma in the study
      population was 160/100 000. CONCLUSIONS: This study confirms the benefits of
      developing a targeted screening strategy in primary care. In particular, after
      the annual reminder, patient participation and the diagnosis of melanoma remained
      high in the patients at elevated risk of thick melanomas. TRIAL REGISTRATION
      NUMBER: NCT01610531.

PMID- 26224017
TI  - Retrospective study using MRI to measure depths of acupuncture points in neck and
      shoulder region.
AB  - OBJECTIVES: There are safety issues associated with acupuncture treatment.
      Previous studies regarding needling depth of acupuncture points revealed
      inconsistent results due to vague depth definition, acupuncture point
      localisation and measuring tools. The objective of this study is to find and
      compare the differences of the mean depths of 11 acupuncture points in the neck
      and shoulder region between subjects, with variables including gender and body
      mass index (BMI). SETTING: This study was conducted at a single medical center in
      Taiwan. PARTICIPANTS: Three hundred and ninety-four participants were included in
      this study. Participants were grouped according to gender and BMI. Acupuncture
      points were localised by WHO standard and measured by MRI. OUTCOME MEASURES: The
      distance from the needle insertion point (surface of the skin) to any tissues
      that would cause possible/severe complications. RESULTS: Mean depths of 11 points
      were obtained in groups of different BMI and gender. Mean depths of all
      participants regardless of BMI and gender are as follows, in centimetres:
      GB21=5.6, SI14=5.2, SI15=8.8, GV15=4.9, GV16=4.6, GB20=5.0, ST9=1.6, SI16=1.8,
      SI17=2.4, TE16=3.1, LI18=1.3. Participants with higher BMI had greater measured
      depths in both gender groups. Male participants had larger mean depths than
      female participants regardless of BMI except in SI17 and LI18. When taking BMI
      into consideration, depths in male participants are greater than in female
      participants in most of the points except the following: GB21, TE16 in obesity
      group; ST9 in underweight and obesity group; SI16 in ideal body weight,
      overweight and obesity group; SI17, LI18 in each group. CONCLUSIONS: Participants
      with higher BMI had greater measured depths and males tended to have greater
      depths in most of the points. Clinical practitioners are recommended to consider
      this information to prevent complications when applying acupuncture treatment to
      their patients.

PMID- 26224018
TI  - Prevalence and determinants of excessive daytime sleepiness in hypertensive
      patients: a cross-sectional study in Douala, Cameroon.
AB  - OBJECTIVE: To determine the prevalence and determinants of excessive daytime
      sleepiness (EDS) among a group of sub-Saharan Africans living with hypertension.
      DESIGN: A cross-sectional study. SETTING: Cardiology outpatient unit of the
      Douala General Hospital in Cameroon. PARTICIPANTS: Patients aged 15 years and
      over, being followed for hypertension between 1st January and 31st July 2013.
      Patients with unstable heart failure, stroke and head trauma were excluded. MAIN
      OUTCOME MEASURE: EDS was the outcome of interest. It was defined as an Epworth
      sleeping scale greater or equal to 10. Logistic regression was used to identify
      factors associated with EDS. RESULTS: A total of 411 patients participated in
      this study, with a sex ratio (male/female) of 0.58 and a mean age of 55.56 years.
      No patient was underweight and the mean body mass index was 30 kg/m(2).
      Controlled blood pressure was found in 92 (22.4%) patients. The prevalence of EDS
      was 62.78% (95% CI 58.08 to 67.47). The factors independently associated with EDS
      were: type 2 diabetes (OR 2.51; 95% CI 1 to 6.29), obesity (OR 2.75; 95% CI 1.52
      to 4.97), snoring (OR 7.92; 95% CI 4.43 to 14.15) and uncontrolled blood pressure
      (OR 4.34; 95% CI 2.24 to 8.40). CONCLUSIONS: A significant proportion of
      hypertensive patients suffer from EDS and present a high risk of sleep apnoea.
      Preventive measures targeted on weight loss, type 2 diabetes and snoring should
      be considered among these patients.

PMID- 26224019
TI  - A favourable prognostic marker for EGFR mutant non-small cell lung cancer:
      immunohistochemical analysis of MUC5B.
AB  - OBJECTIVES: To determine the use of the mucin proteins MUC5B and MUC5AC as
      prognosis markers for non-small cell lung cancer (NSCLC) carrying epidermal
      growth factor receptor (EGFR) mutations. SETTING: Patients who underwent surgical
      resection at Nagasaki University Hospital and related facilities in Japan between
      June 1996 and March 2013. PARTICIPANT: 159 Japanese patients (male: n=103;
      female: n=56) with NSCLC, who underwent surgical resection (EGFR-mutant type:
      n=78, EGFR wild type: n=81). RESULTS: Patients whose tumours expressed MUC5B had
      significantly longer overall survival and relapse-free survival compared to the
      MUC5B-negative patients with EGFR mutant NSCLC (p=0.0098 and p=0.0187,
      respectively). In patients with EGFR wild-type NSCLC, there was no association
      with MUC5B expression. MUC5AC expression was not different between EGFR mutant
      and wild-type NSCLC. CONCLUSIONS: Present findings indicate that MUC5B, but not
      MUC5AC, is a novel prognostic biomarker for patients with NSCLC carrying EGFR
      mutations but not for patients with NSCLC carrying wild-type EGFR.

PMID- 26224021
TI  - Impact of Performance-Based Financing in a Low-Resource Setting: A Decade of
      Experience in Cambodia.
AB  - This paper exploits the geographic expansion of performance-based financing (PBF)
      in Cambodia over a decade to estimate its effect on the utilization of maternal
      and child health services. PBF is estimated to raise the proportion of births
      occurring in incentivized public health facilities by 7.5 percentage points
      (25%). A substantial part of this effect arises from switching the location of
      institutional births from private to public facilities; there is no significant
      impact on deliveries supervised by a skilled birth attendant, nor is there any
      significant effect on neonatal mortality, antenatal care and vaccination rates.
      The impact on births in public facilities is much greater if PBF is accompanied
      by maternity vouchers that cover user fees, but there is no significant effect
      among the poorest women. Heterogeneous effects across schemes differing in design
      suggest that maintaining management authority within a health district while
      giving explicit service targets to facilities is more effective in raising
      utilization than contracting management to a non-governmental organization while
      denying it full autonomy and leaving financial penalties vague. Copyright (c)
      2015 John Wiley & Sons, Ltd.

PMID- 26224022
TI  - Traumatic brain injury and bipolar psychosis in the Genomic Psychiatry Cohort.
AB  - Approximately three million individuals in the United States sustain traumatic
      brain injury (TBI) every year, with documented impact on a range of neurological
      and psychiatric disturbances including mania, depression, and psychosis.
      Identification of subsets of individuals that may demonstrate increased
      propensity for posttraumatic symptoms and who may share genetic vulnerabilities
      for gene-environment interactions can enhance efforts to understand, predict, and
      prevent these phenomena. A sample of 11,489 cases from the Genomic Psychiatry
      Cohort (GPC), a NIMH-managed data repository for the investigation of
      schizophrenia and bipolar disorder, was used for this study. Cases were excluded
      if TBI was deemed causal to their mental illness. A k-means clustering algorithm
      was used to probe differences between schizophrenia and bipolar disorder
      associated with variables including onset age, hallucinations, delusions, head
      injury, and TBI. Cases were separated into an optimum number of seven clusters,
      with two clusters including all cases with brain injury. Bipolar disorder with
      psychosis and TBI were significantly correlated in one cluster in which 72% of
      cases were male and 99.2% sustained head injury. This cluster also carried the
      longest average period of unconsciousness. This study demonstrates an association
      of TBI with psychosis in a subset of bipolar cases, suggesting that traumatic
      stressors may have the ability to impact gene expression in a vulnerable
      population, and/or there is a heightened occurrence of TBI in individuals with
      underlying psychosis. Further studies should more closely examine the interplay
      between genetic variation in bipolar disorder and susceptibility to psychosis
      following TBI. (c) 2015 Wiley Periodicals, Inc.

PMID- 26224020
TI  - A peptide resource for the analysis of Staphylococcus aureus in host-pathogen
      interaction studies.
AB  - Staphylococcus aureus is an opportunistic human pathogen, which can cause life
      threatening disease. Proteome analyses of the bacterium can provide new insights
      into its pathophysiology and important facets of metabolic adaptation and, thus,
      aid the recognition of targets for intervention. However, the value of such
      proteome studies increases with their comprehensiveness. We present an MS-driven,
      proteome-wide characterization of the strain S. aureus HG001. Combining 144 high
      precision proteomic data sets, we identified 19 109 peptides from 2088 distinct
      S. aureus HG001 proteins, which account for 72% of the predicted ORFs. Peptides
      were further characterized concerning pI, GRAVY, and detectability scores in
      order to understand the low peptide coverage of 8.7% (19 109 out of 220 245
      theoretical peptides). The high quality peptide-centric spectra have been
      organized into a comprehensive peptide fragmentation library (SpectraST) and used
      for identification of S. aureus-typic peptides in highly complex host-pathogen
      interaction experiments, which significantly improved the number of identified S.
      aureus proteins compared to a MASCOT search. This effort now allows the
      elucidation of crucial pathophysiological questions in S. aureus-specific host
      pathogen interaction studies through comprehensive proteome analysis. The S.
      aureus-specific spectra resource developed here also represents an important
      spectral repository for SRM or for data-independent acquisition MS approaches.
      All MS data have been deposited in the ProteomeXchange with identifier PXD000702
      (http://proteomecentral.proteomexchange.org/dataset/PXD000702). 

PMID- 26224023
TI  - A One-Step Staining Probe for Phosphatidylethanolamine.
AB  - Phosphatidylethanolamine (PE) is an abundant phospholipid in cellular membranes,
      but relatively little is known about the kinetics of PE in biological membrane
      systems. Characterizing PE on a cellular level has been challenging owing to a
      lack of proper molecular tools. The lantibiotic duramycin and its structural
      analogue, cinnamycin, are currently the only known polypeptides that have an
      established stereospecific structure for binding membrane PE with high affinity
      and high specificity. These lantibiotics are recognized for their potential as
      molecular probes for studying PE kinetics in various membranes. However, owing to
      their antibiotic nature, duramycin and cinnamycin exhibit appreciable levels of
      cytotoxicity at low micromolar concentrations in cultured mammalian cells by
      inducing membrane distortion and possible PE redistribution. These issues can
      potentially complicate study design and data interpretation. Here, we report the
      construction of a molecular probe consisting of duramycin attached to the C
      terminus of green fluorescent protein (GFP) by a PEG linker at a stoichiometry of
      1. The construct retained specific binding toward PE and essentially no
      cytotoxicity compared to native duramycin. The biological utilities of this probe
      were demonstrated in a number of cellular staining studies involving PE dynamics.
      The availability of a one-step, nontoxic molecular probe for PE will enable
      characterization of the biology of this important phospholipid.

PMID- 26224024
TI  - Mitral Annular Calcification and Cardiovascular Diseases: Does Correlation Imply
      Causation?

PMID- 26224025
TI  - Ant trophallactic networks: simultaneous measurement of interaction patterns and
      food dissemination.
AB  - Eusocial societies and ants, in particular, maintain tight nutritional regulation
      at both individual and collective levels. The mechanisms that underlie this
      control are far from trivial since, in these distributed systems, information
      about the global supply and demand is not available to any single individual.
      Here we present a novel technique for non-intervening frequent measurement of the
      food load of all individuals in an ant colony, including during trophallactic
      events in which food is transferred by mouth-to-mouth feeding. Ants are imaged
      using a dual camera setup that produces both barcode-based identification and
      fluorescence measurement of labeled food. This system provides detailed
      measurements that enable one to quantitatively study the adaptive food
      distribution network. To demonstrate the capabilities of our method, we present
      sample observations that were unattainable using previous techniques, and could
      provide insight into the mechanisms underlying food exchange. 

PMID- 26224026
TI  - Association between maternal dental periapical infections and pregnancy outcomes:
      results from a cross-sectional study in Malawi.
AB  - OBJECTIVES: Maternal infections are associated with intrauterine growth
      restriction (IUGR) and preterm birth (PTB). Dental infections are common in low
      income settings, but their contribution to adverse pregnancy outcomes is unknown.
      We studied the epidemiology of dental periapical infections among pregnant women
      and their association to foetal growth restriction and the duration of pregnancy
      in a rural sub-Saharan African population. METHODS: This was a cross-sectional
      study on the association between maternal dental periapical infections and birth
      outcomes, in Malawi, Africa. We assessed oral health clinically and
      radiologically among recently delivered women with known duration of pregnancy
      and measured birthweight (BW), length and head circumference of their infants.
      RESULTS: Of 1024 analysed participants, 23.5% had periapical infections. Mean
      duration of pregnancy was 39.4 weeks, BW 2979 g and length 49.7 cm. Women with
      periapical infection had mean (95% CI) pregnancy duration 0.4 weeks (0.1-0.8)
      shorter and delivered infants with 79 g (13-145) lower BW and 0.5 cm (0.2-0.9)
      shorter neonatal length than women without periapical infection. The incidence of
      PTB was 10.0% among women with periapical infection and 7.3% among those without
      (adjusted difference 3.5%, 95% CI -1.1-8.1%). Corresponding prevalences for
      stunting were 20.9% and 14.2% (adjusted difference 9.0%, 95% CI 2.7%-15.2%). The
      population-attributable risk fraction attributable to periapical infection was
      9.7% for PTB and 12.8% for stunting. CONCLUSIONS: Periapical infection was
      associated with shorter pregnancy duration and IUGR in the study area;
      interventions addressing this risk factor may improve birth outcomes in low
      income settings.

PMID- 26224027
TI  - Spiranthes sinensis Suppresses Production of Pro-Inflammatory Mediators by Down
      Regulating the NF-kappaB Signaling Pathway and Up-Regulating HO-1/Nrf2 Anti
      Oxidant Protein.
AB  - Spiranthes sinensis is an east Asian wild orchid used in Chinese folk medicine.
      In this study, an ethyl acetate fraction from S. sinensis(SSE) was found to
      suppress the production of LPS-stimulated inflammatory mediators in RAW264.7
      cells and BALB/c mice. SSE inhibited the production of pro-inflammatory mediators
      such as nitric oxide (NO), prostaglandin E2 (PGE2), tumo necrosis factor-alpha
      (TNF-alpha), IL-1beta, and IL-6 in LPS-stimulated RAW264.7 cells. SSE also
      significantly suppressed LPS-stimulated protein levels of iNOS and mPGES-1 by
      blocking IkappaB phosphorylation, NF-kappaB nuclear translocation, and MAPKs
      phosphorylation. In addition, SSE treatment also enhanced protein levels of HO-1
      and anti-oxidant enzymes (SOD-1, CAT, and GPx-1) through the nuclear
      translocation of Nrf2 in LPS-stimulated RAW264.7 cells. In vivo, we demonstrated
      that SSE attenuated the levels of pro-inflammatory mediators (NO, TNF-alpha, IL
      1beta, and IL-6), ALT, and AST in the serum of LPS-stimulated BALB/c mice.
      Western blotting revealed that SSE enhanced HO-1 expression in lung and liver
      tissue after LPS injection in mice. These results suggest that the anti
      inflammatory properties of SSE involve the suppression of iNOS, mPGES-1, and
      inflammatory mediators by inducing the HO-1 pathway in LPS-stimulated RAW264.7
      cells and BALB/c mice. 

PMID- 26224028
TI  - Inhibitory Effects of Epimedium Herb on the Inflammatory Response In Vitro and In
      Vivo.
AB  - Epimedium Herb (EH) is a medicinal herb used in traditional Eastern Asia. In this
      study described, we investigated the biological effects of Epimedium Herb water
      extract (EHWE) on lipopolysaccharide (LPS)-mediated inflammation in macrophages
      and local inflammation in vivo. We also investigated the biological effects of
      EHWE on the production of inflammatory mediators, pro-inflammatory cytokines and
      related products, as well as nuclear factor kappaB (NF-kappaB) and mitogen
      activated protein kinase (MAPK) activation in LPS-stimulated macrophages. The
      analgesic effect of the acetic acid-induced writhing response and inhibitory
      activity on xylene-induced ear edema was also evaluated in mice. EHWE exhibited
      anti-inflammatory effects by inhibiting the production of nitric oxide (NO),
      interleukin (IL)-6 and IL-1beta. In addition, EHWE strongly suppressed inducible
      nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO
      1) expression, and inhibited NF-kappaB activation as well as MAPK pathway
      phosphorylation. Furthermore, EHWE exhibited an analgesic effect on the writhing
      response and an inhibitory effect on ear edema in mice. For the first time, we
      demonstrated the anti-inflammatory effects and inhibitory mechanism in
      macrophages, as well as the inhibitory activity of EHWE in vivo. Our results
      indicate a potential use of EHWE as an inflammatory therapeutic agent developed
      from a natural substance. 

PMID- 26224029
TI  - Anemone altaica Induces Apoptosis in Human Osteosarcoma Cells.
AB  - In the past decade, no significant improvement has been made in chemotherapy for
      osteosarcoma (OS). To develop improved agents against OS, we screened 70 species
      of medicinal plants and treated two human OS cell lines with different agent
      concentrations. We then examined cell viability using the MTT assay. Results
      showed that a candidate plant, particularly the rhizomes of Anemone altaica
      Fisch. ex C. A. Mey aqueous extract (AAE), suppressed the viability of HOS and
      U2OS cells in a concentration-dependent manner. Flow cytometry analysis revealed
      that AAE significantly increased the amount of cell shrinkage (Sub-G1 fragments)
      in HOS and U2OS cells. Moreover, AAE increased cytosolic cytochrome c and Bax,
      but decreased Bcl-2. The amount of cleaved caspase-3 and poly-(ADP-ribose)
      polymerase-1 (PARP-1) were significantly increased. AAE suppressed the growth of
      HOS and U2OS through the intrinsic apoptotic pathway. Data suggest that AAE is
      cytotoxic to HOS and U2OS cells and has no significant influence on human
      osteoblast hFOB cells. The high mRNA levels of apoptosis-related factors
      (PPP1R15A, SQSTM1, HSPA1B, and DDIT4) and cellular proliferation markers (SKA2
      and BUB1B) were significantly altered by the AAE treatment of HOS and U2OS cells.
      Results show that the anticancer activity of AAE could up-regulate the expression
      of a cluster of genes, especially those in the apoptosis-related factor family
      and caspase family. Thus, AAE has great potential as a useful therapeutic drug
      for human OS. 

PMID- 26224030
TI  - Ameliorative Effect of Aspalathin and Nothofagin from Rooibos (Aspalathus
      linearis) on HMGB1-Induced Septic Responses In Vitro and In Vivo.
AB  - The ubiquitous nuclear protein, high mobility group box 1 (HMGB1), is released by
      activated macrophages and human umbilical vein endothelial cells (HUVECs) and
      functions as a late mediator of experimental sepsis. Aspalathin (Asp) and
      nothofagin (Not), which have been reported to have anti-oxidant activity, are the
      two major active dihydrochalcones found in green rooibos. In this study, we
      investigated the antiseptic effects and underlying mechanisms of Asp and Not
      against HMGB1-mediated septic responses in HUVECs and mice. The anti-inflammatory
      activities of Asp and Not were determined by measuring permeability, monocyte
      adhesion and migration, and activation of proinflammatory proteins in HMGB1
      activated HUVECs and mice. According to the results, Asp and Not effectively
      inhibited lipopolysaccharide (LPS)-induced release of HMGB1, and suppressed HMGB1
      mediated septic responses, such as hyperpermeability, adhesion and migration of
      leukocytes, and expression of cell adhesion molecules. In addition, Asp and Not
      suppressed the production of tumor necrosis factor alpha (TNF-alpha) and
      interleukin 6 (IL-6), the activation of nuclear factor-kappaB (NF-kappaB) and
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) by HMGB1. Collectively,
      these results indicate that Asp and Not could be potential therapeutic agents for
      the treatment of various severe vascular inflammatory diseases via the inhibition
      of the HMGB1 signaling pathway. 

PMID- 26224031
TI  - Evaluation of Cognitive Symptoms Following Concussion.
AB  - The assessment of cognitive symptoms following concussion has evolved over the
      last several decades as a distinct focus in research and an essential component
      of clinical decision making and management. The aims of this paper are to (1)
      identify issues related to assessment of postconcussion cognitive functioning and
      (2) provide a review of common self-report and performance-based measures,
      including computerized-based assessments (CBAs), and, more traditional,
      comprehensive neuropsychological evaluations. We conclude that (1) there has yet
      to emerge one cognitive-symptom measurement method that can be considered the
      "gold standard" for all settings, (2) the usefulness of cognitive symptoms
      assessment findings in the clinical management decisions rests a great deal on
      the background of the practitioner, and (3) cognitive-symptom assessment needs to
      be considered in the context of a broader evaluation of other postconcussion
      symptoms. 

PMID- 26224032
TI  - Selective balloon-occluded transarterial chemoembolization for patients with one
      or two hepatocellular carcinoma nodules: Retrospective comparison with
      conventional super-selective TACE.
AB  - AIM: Selective balloon-occluded transarterial chemoembolization (B-TACE) enables
      strong TACE; infusion of more volume of lipiodol emulsion and forceful injection
      of embolization materials. The aim of this study is to analyze the efficacy of B
      TACE for patients with one or two hepatocellular carcinoma (HCC) nodules compared
      with conventional super-selective TACE using a microcatheter (C-TACE). METHODS:
      We retrospectively selected patients without previous history of TACE, with one
      or two HCC nodules, with performance status 0/1, and with liver function of Child
      Pugh score A/B. Between 2008 and 2010, a 3-Fr microballoon catheter was used for
      targeted TACE (B-TACE group). Between 2005 and 2008, a 2-Fr microcatheter was
      used (C-TACE group). Control rates of primary nodule, overall survival rates and
      tumor-free rates in the liver were calculated for each group using the Kaplan
      Meier method. Univariate analysis was performed to compare between the groups
      using the log-rank test. Multivariate analysis was performed for analysis of
      prognostic factors using Cox's proportional hazard model. The factors were B-TACE
      versus C-TACE, Child-Pugh score A versus B, single nodule versus double, large
      nodule versus small , elder versus not, and prior radiofrequency ablation
      treatment versus not. RESULTS: Control rates of the primary nodule were improved
      by B-TACE. B-TACE was an independent factor to improve both control rates of the
      primary nodule and overall survival rates. Child-Pugh score A was an independent
      factor to increase overall survival rates. There was no statistically significant
      difference in overall survival or tumor-free survival rates between the groups.
      CONCLUSION: B-TACE was an independent factor to improve overall survival rates on
      multivariate analysis, but there was no significant difference in overall
      survival rates between B-TACE and C-TACE groups on univariate analysis.

PMID- 26224033
TI  - Gold-Catalyzed Reductive Transformation of Nitro Compounds Using Formic Acid:
      Mild, Efficient, and Versatile.
AB  - Developing new efficient catalytic systems to convert abundant and renewable
      feedstocks into valuable products in a compact, flexible, and target-specific
      manner is of high importance in modern synthetic chemistry. Here, we describe a
      versatile set of mild catalytic conditions utilizing a single gold-based solid
      catalyst that enables the direct and additive-free preparation of four distinct
      and important amine derivatives (amines, formamides, benzimidazoles, and
      dimethlyated amines) from readily available formic acid (FA) and nitro starting
      materials with high level of chemoselectivity. By controlling the stoichiometry
      of the employed FA, which has attracted considerable interest in the area of
      sustainable chemistry because of its potential as an entirely renewable hydrogen
      carrier and as a versatile C1 source, a facile atom- and step-efficient
      transformation of nitro compounds can be realized in a modular fashion. 

PMID- 26224034
TI  - Comparison of train-of-four count by anesthesia providers versus TOF-Watch(r) SX:
      a prospective cohort study.
AB  - PURPOSE: Qualitative monitoring of neuromuscular blockade using the train-of-four
      (TOF) count is widely used to determine the timing and dose of reversal agents
      for neuromuscular blockade. We compared TOF count measured manually by anesthesia
      providers with that determined by TOF-Watch(r) SX. METHODS: This prospective
      observational cohort study included patients who were American Society of
      Anesthesiologists physical status III or less and undergoing elective surgery.
      During recovery from an intubating dose of rocuronium or vecuronium, the TOF
      count was measured every 15 sec using TOF-Watch SX. Anesthesia providers assessed
      the TOF count twice at each level of TOF-count, 15 sec after the TOF-Watch SX
      count increased to the next level and then two to five minutes later. RESULTS: In
      75 patients, 687 observations were collected. There was agreement between the TOF
      Watch SX and the subjective assessment by the provider in 386 (56%) of these
      observations. The agreement was 87% at TOF counts of 0 and 4. In the 409
      observations at TOF counts 1, 2, and 3, the agreement was 36%. Among the 264
      observations with disagreement at these TOF counts, providers assessed a higher
      TOF count in 254 (96%) observations and a lower count in 10 (4%) observations
      compared with the TOF-Watch SX. CONCLUSION: Anesthesia providers report higher
      values of TOF count compared with the TOF-Watch SX, especially at intermediate
      levels of neuromuscular blockade. Since the dosing guidelines for the timing and
      dose of reversal agents are based on the TOF count derived from the TOF-Watch SX,
      a manually assessed TOF count may lead to inadequate dosing and/or premature
      administration of reversal agents.

PMID- 26224035
TI  - Effects of confinement, surface-induced orientations and strain on dynamical
      behaviors of bacteria in thin liquid crystalline films.
AB  - We report on the organization and dynamics of bacteria (Proteus mirabilis)
      dispersed within lyotropic liquid crystal (LC) films confined by pairs of
      surfaces that induce homeotropic (perpendicular) or hybrid (homeotropic and
      parallel orientations at each surface) anchoring of the LC. By using motile
      vegetative bacteria (3 um in length) and homeotropically aligned LC films with
      thicknesses that exceed the length of the rod-shaped cells, a key finding
      reported in this paper is that elastic torques generated by the LC are
      sufficiently large to overcome wall-induced hydrodynamic torques acting on the
      cells, thus leading to LC-guided bacterial motion near surfaces that orient LCs.
      This result extends to bacteria within LC films with hybrid anchoring, and leads
      to the observation that asymmetric strain within a hybrid aligned LC rectifies
      motions of motile cells. In contrast, when the LC film thickness is sufficiently
      small that confinement prevents alignment of the bacteria cells along a
      homeotropically aligned LC director (achieved using swarm cells of length 10-60
      um), the bacterial cells propel in directions orthogonal to the director,
      generating transient distortions in the LC that have striking "comet-like"
      optical signatures. In this limit, for hybrid LC films, we find LC elastic
      stresses deform the bodies of swarm cells into bent configurations that follow
      the LC director, thus unmasking a coupling between bacterial shape and LC strain.
      Overall, these results provide new insight into the influence of surface-oriented
      LCs on dynamical bacterial behaviors and hint at novel ways to manipulate
      bacteria using confined LC phases that are not possible in isotropic solutions. 

PMID- 26224036
TI  - Diastereoselective synthesis of cyclopentanoids: applications to the construction
      of the ABCD tetracyclic core of retigeranic acid A.
AB  - A concise and efficient approach for the construction of the tetracyclic carbon
      skeleton of retigeranic acid A is described. The key transformations include a
      novel Rh-catalyzed [3+2] cycloaddition of enyol to afford cyclopentanoid E,
      bearing two contiguous quaternary stereocenters at the bridgehead positions, and
      an intramolecular Pauson-Khand reaction to construct the advanced tetracyclic
      core structure of retigeranic acid A. 

PMID- 26224037
TI  - No association of FAM47E rs6812193, SCARB2 rs6825004 and STX1B rs4889603
      polymorphisms with Parkinson's disease in a Chinese Han population.
AB  - Recently, a series of studies found that the single-nucleotide polymorphisms
      (SNPs) rs6812193 in the family with sequence similarity 47, member E (FAM47E),
      rs6825004 in the scavenger receptor class B member 2 (SCARB2) and rs4889603 in
      the Syntaxin1B (STX1B) genes increase the risk for Parkinson's disease (PD).
      However, the results of subsequent independent studies were inconsistent. To
      explore the associations between the three SNPs and PD in the Chinese population,
      a large cohort was analyzed in a case-control study. A total of 1994 subjects,
      including 1179 PD and 815 healthy controls (HCs), were investigated. All subjects
      were genotyped for rs6812193, rs6825004 and rs4889603 using the Sequenom iPLEX
      Assay. There was no significant difference in additive genetic model of
      rs6812193, rs6825004 and rs4889603 between PD and controls, even after being
      stratified by sex and age. In addition, no significant differences were found
      between other subgroups of PD patients with regard to clinical presentation. Our
      findings suggested that FAM47E rs6812193, SCARB2 rs6825004 and STX1B rs4889603 do
      not confer a significant risk for PD in Chinese population. 

PMID- 26224038
TI  - Early Parkinson's disease patients on rasagiline present with better odor
      discrimination.
AB  - The effects of rasagiline on olfaction in animal studies are convincing. However,
      apart from various anecdotal patient reports, they could not be reproduced in
      prospective studies in humans. Cross-sectional data of large patient groups are
      still missing. The aim of this study was therefore to determine the olfactory
      function in a broad heterogeneous Parkinson's disease (PD) population with and
      without rasagiline intake. In this single-center, cross-sectional study 224 PD
      patients with and without rasagiline (1 mg/day) participated. Seventy-four of
      them received rasagiline as mono, or adjunct therapy. One-hundred fifty patients
      were untreated or received PD medication other than rasagiline. Comprehensive
      olfactory testing was performed for phenyl-ethyl alcohol odor thresholds, odor
      discrimination, and odor identification. Olfactory function did not differ
      between the two treatment groups with disease duration up to 29 years. Rasagiline
      treated patients with disease duration of less than 8 years, however, presented
      with significant better odor discrimination abilities compared to PD patients
      without rasagiline treatment. This effect was no longer evident in patients with
      longer disease duration and proofed to be independent of age, sex, and
      medication. Our results may suggest that rasagiline treatment has a positive
      effect on the processing of olfactory information in early PD. 

PMID- 26224039
TI  - Neoadjuvant Chemoradiotherapy and Surgery Versus Surgery Alone in Resectable
      Pancreatic Cancer: A Single-Center Prospective, Randomized, Controlled Trial
      Which Failed to Achieve Accrual Targets.
AB  - OBJECTIVE: The objective of the study is to evaluate the usefulness of
      neoadjuvant chemoradiotherapy in resectable pancreatic cancer. METHODS: A single
      center RCT of patients affected by resectable pancreatic adenocarcinoma which
      included arm A (surgery alone) and arm B (neoadjuvant chemoradiation and
      surgery). The primary endpoint was R0 resection; the secondary endpoints were
      toxicity; number of patients who completed the neoadjuvant therapy; radiological
      and pathological response after chemoradiation; and pTNM stage, postoperative
      morbidity, mortality, and overall and disease-free survival. A sample size of 32
      patients was required for each group. RESULTS: The study was terminated early,
      and 38 patients were randomized: 20 in arm A and 18 in arm B. There was no
      significant difference regarding R0 resection rate in the two groups (intention
      to-treat, OR = 1.91, P = 0.489). Neoadjuvant chemoradiotherapy was completed in
      14 out of 18 cases (77.8 %) and the radiological and pathological response was
      efficacious in 72.3 and 90.9 % of cases, respectively. CONCLUSIONS: Neoadjuvant
      chemoradiation was feasible, safe, and efficacious, although non-significant
      results were obtained as a result of the underpowered data due to the difficulty
      in recruiting patients. Additional multicenter RCTs are needed in the future.

PMID- 26224041
TI  - Changes in the Factors Influencing Public Acceptance of Nuclear Power Generation
      in Japan Since the 2011 Fukushima Daiichi Nuclear Disaster.
AB  - Public support for nuclear power generation has decreased in Japan since the
      Fukushima Daiichi nuclear accident in March 2011. This study examines how the
      factors influencing public acceptance of nuclear power changed after this event.
      The influence factors examined are perceived benefit, perceived risk, trust in
      the managing bodies, and pro-environmental orientation (i.e., new ecological
      paradigm). This study is based on cross-sectional data collected from two online
      nationwide surveys: one conducted in November 2009, before the nuclear accident,
      and the other in October 2011, after the accident. This study's target
      respondents were residents of Aomori, Miyagi, and Fukushima prefectures in the
      Tohoku region of Japan, as these areas were the epicenters of the Great East
      Japan Earthquake and the locations of nuclear power stations. After the accident,
      trust in the managing bodies was found to have a stronger influence on perceived
      risk, and pro-environmental orientation was found to have a stronger influence on
      trust in the managing bodies; however, perceived benefit had a weaker positive
      influence on public acceptance. We also discuss the theoretical and practical
      implications of these findings. 

PMID- 26224040
TI  - Defining a Subgroup Treatable for Laparoscopic and Endoscopic Cooperative Surgery
      in Undifferentiated Early Gastric Cancer: the Role of Lymph Node Metastasis.
AB  - BACKGROUND: Recently, the use of endoscopic submucosal dissection (ESD) for early
      gastric cancer (EGC) and the development of laparoscopic and endoscopic
      cooperative surgery (LECS) have enabled either the preservation of the stomach or
      the minimization of the extent of partial resection. ESD has recently been
      practiced on a differentiated type of EGC. However, there is no clear evidence
      for endoscopic treatments of undifferentiated EGC. The purposes of this study are
      to investigate predictive factors of lymph node metastasis (LNM) in
      undifferentiated EGC and expand the possibility of using LECS for the treatment
      of undifferentiated EGC. METHODS: Data from 116 patients with undifferentiated
      EGC and surgically treated were collected, and the association between the
      clinicopathological factors and the presence of LNM was retrospectively analyzed
      by univariate and multivariate logistic regression analyses. Odds ratios (OR)
      with 95 % confidence interval (95 % CI) were calculated. RESULTS: The tumor size
      (OR = 11.748, 95 % CI 2.034-62.213, P = 0.008), depth of invasion (OR = 13.928,
      95 % CI 1.971-92.434, P = 0.016), and lymphatic vessel involvement (OR = 11.522,
      95 % CI 2.645-59.172, P = 0.021) that were significantly associated with LNM by
      univariate analysis were found to be significant and independent risk factors for
      LNM by multivariate analysis. The LNM rate was 5.9 % (4/68) and 29.2 % (14/48)
      with intramucosal and submucosal undifferentiated EGC, respectively. LNM was
      observed in 66.7 % (2/3) of patients with both risk factors (tumor larger than or
      equal to 2.0 cm and the presence of lymphatic vessel involvement (LVI)), but in
      none of 36 patients without the two risk factors in intramucosal undifferentiated
      EGC. The 5-year survival rates were 88.9, 72.4, and 33.3 %, respectively, in
      cases with none, one, and two of the risk factors, respectively, in intramucosal
      undifferentiated EGC (P < 0.05). CONCLUSIONS: ESD alone may be a sufficient
      treatment for intramucosal undifferentiated EGC if the tumor is less than 2.0 cm
      in size and when LVI is absent upon postoperative histological examination. LECS
      is feasible and safe for patients with undifferentiated EGC.

PMID- 26224042
TI  - Evaluation of blood neutrophil to lymphocyte and platelet to lymphocyte ratios
      according to plasma glucose status and serum insulin-like growth factor 1 levels
      in patients with acromegaly.
AB  - INTRODUCTION: Cardiovascular, respiratory, and cerebrovascular diseases and
      malignancies are responsible for morbidity and mortality in acromegaly. Also
      these diseases are associated with chronic inflammation. The neutrophil to
      lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are currently
      gaining interest as new markers of inflammation. Moreover, increased morbidity
      and mortality are positively correlated with the presence of diabetes and levels
      of insulin-like growth factor 1 (IGF-1) in acromegaly. The objective of the
      present study was to investigate the relationship between these markers and
      acromegaly according to plasma glucose status and serum IGF-1 levels. MATERIALS
      AND METHODS: We retrospectively analyzed data from 61 acromegaly patients who
      were in a newly diagnosed period (35 male, 26 female; mean age 38.13 +/- 13.98).
      Patients with normal plasma glucose (n = 27), impaired fasting glucose (n = 18),
      and diabetes mellitus (n = 16) were categorized into three different groups. NLR
      and PLR were compared between the study groups and were evaluated according to
      IGF-1 levels. RESULTS: There were no statistically significant differences in NLR
      and PLR measurements among the study groups (p > 0.05). However, there were
      significant positive correlations between NLR and IGF-1 levels and between PLR
      and IGF-1 levels when all patients were evaluated (r = 0.334, p = 0.011 and r =
      0.277, p = 0.035, respectively). CONCLUSIONS: This is the first report studying
      the relationship of NLR and PLR with glucose status and IGF-1 levels in
      acromegaly patients. Our study results suggest that subclinical inflammation may
      play a role in increased incidence of mortality and morbidity, which depends on
      uncontrolled IGF-1 levels in patients with acromegaly.

PMID- 26224043
TI  - Iron overload induced by ferric ammonium citrate triggers reactive oxygen species
      mediated apoptosis via both extrinsic and intrinsic pathways in human hepatic
      cells.
AB  - BACKGROUND: Hepatic iron overload is common in patients with myelodysplastic
      syndromes undergoing hematopoietic cell transplantation (HCT) and may predispose
      to peri- and post-HCT toxicity. To better understand the mechanisms of iron
      overload-induced liver injury, we examined the effects of iron overload induced
      by ferric ammonium citrate (FAC) on oxidative stress and apoptosis signaling
      pathway in human hepatic cell line HH4. METHODS AND RESULTS: Hepatic HH4 cells
      were exposed to FAC to force iron uptake, and cellular responses were determined.
      Incubation with 5 mM FAC resulted in increased intracellular iron content in a
      time-dependent manner. High concentration of FAC impaired cell viability and
      increased level of reactive oxygen species (ROS), and addition of antioxidant
      reagent such as glutathione or N-acetylcysteine dramatically reduced FAC-induced
      intracellular ROS generation. FAC overload significantly increased the
      phosphorylation of inhibitor of kappaB-alpha, p38 mitogen-activated protein
      kinase (MAPK), and nuclear factor kappa light chain enhancer of activated B cells
      (NF-kappaB) p65 and promoted the nuclear translocation of NF-kappaB p65.
      Knockdown of Fas and Bid expression by small interfering RNA in iron-treated HH4
      cells resulted in restoration of cell viability. CONCLUSIONS: We reported that
      FAC treatment is capable of inducing both extrinsic death receptor and intrinsic
      mitochondrial signaling pathway-mediated HH4 cells apoptosis through ROS
      activated p38 MAPK and NF-kappaB pathways.

PMID- 26224044
TI  - Beneficial effects of carnosine and carnosine plus vitamin E treatments on
      doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in
      rats.
AB  - OBJECTIVE: Oxidative stress plays an important role in doxorubicin (DOX)-induced
      toxicity. Carnosine (CAR) is a dipeptide with antioxidant properties. The aim of
      this study was to evaluate the decreasing or preventive effect of CAR alone or
      combination with vitamin E (CAR + Vit E) on DOX-induced toxicity in heart, liver,
      and brain of rats. METHODS: Rats were treated with CAR (250 mg kg(-1) day(-1);
      intraperitoneally (i.p.)) or CAR + Vit E (equals 200 mg kg(-1) alpha-tocopherol;
      once every 3 days; intramuscularly) for 12 consecutive days. On the 8th day of
      treatment, rats were injected with a single dose of DOX (30 mg kg(-1), i.p.).
      Serum cardiac troponin I (cTnI), urea, and creatinine levels; alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) activities; and
      oxidative stress parameters in tissues were measured. We also determined
      thiobarbituric acid reactive substances, diene conjugate, protein carbonyl (PC),
      and glutathione levels and antioxidant enzyme activities. RESULTS: DOX resulted
      in increased serum cTnI, ALT, AST, urea, and creatinine levels and increased
      lipid peroxide and PC levels in tissues. CAR or CAR + Vit E treatments led to
      decreases in serum cTnI levels and ALT and AST activities. These treatments
      reduced prooxidant status and ameloriated histopathologic findings in the
      examined tissues. CONCLUSION: Our results may indicate that CAR alone, especially
      in combination with Vit E, protect against DOX-induced toxicity in heart, liver,
      and kidney tissues of rats. This was evidenced by improved cardiac, hepatic, and
      renal markers and restoration of the prooxidant state and amelioration of
      histopathologic changes.

PMID- 26224045
TI  - Severe Mental Illness, Somatic Delusions, and Attempted Mass Murder.
AB  - A case of an attempted mass shooting at a large psychiatric hospital in the
      United States by a 30-year-old male with severe mental illness, somatic
      delusions, and exceptional access to healthcare professionals is reported. Six
      persons were shot, one died at the scene, and the shooter was then killed by the
      police. Data were gathered from court documents and media accounts. An analysis
      of the shooter's psychiatric history, his interactions with healthcare
      professionals, and communications prior to the shooting suggest a rare form of
      mass murder, a random attack by a documented psychotic and delusional individual
      suffering with somatic delusions. Despite his being psychotic, the killer planned
      the attack and made a direct threat 1 month prior to the shootings. This case
      highlights problems with the healthcare system, indicating that it might be ill
      equipped to appropriately deal with severe mental illness.

PMID- 26224046
TI  - Effects of polymorphic variation on the mechanism of Endoplasmic Reticulum
      Aminopeptidase 1.
AB  - Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) generates antigenic peptides for
      loading onto Major Histocompatibility Class I molecules (MHCI) and can regulate
      adaptive immune responses. During the last few years, many genetic studies have
      revealed strong associations between coding Single Nucleotide Polymorphisms
      (SNPs) in ERAP1 and common human diseases ranging from viral infections to cancer
      and autoimmunity. Functional studies have established that these SNPs affect
      enzyme activity resulting to changes in antigenic peptide processing,
      presentation by MHCI and cellular cytotoxic responses. These disease-associated
      polymorphisms are, however, located away from the enzyme's active site and are
      interspersed to different structural domains. As a result, the mechanism by which
      these SNPs can affect function remains largely elusive. ERAP1 utilizes a complex
      catalytic mechanism that involves a large conformational change between inactive
      and active forms and has the unique property to trim larger peptides more
      efficiently than smaller ones. We analyzed two of the most consistently
      discovered disease-associated polymorphisms, namely K528R and Q730E, for their
      effect on the ability of the enzyme to select substrates based on length and to
      undergo conformational changes. By utilizing enzymatic and computational analysis
      we propose that disease-associated SNPs can affect ERAP1 function by influencing:
      (i) substrate length selection and (ii) the conformational distribution of the
      protein ensemble. Our results provide novel insight on the mechanisms by which
      polymorphic variation distal from the active site of ERAP1 can translate to
      changes in function and contribute to immune system variability in humans. 

PMID- 26224047
TI  - Berberine ameliorates TNBS induced colitis by inhibiting inflammatory responses
      and Th1/Th17 differentiation.
AB  - Th1 and Th17 cells, and their associated cytokines, have been associated with the
      pathogenesis of Crohn's disease. Berberine (BBR), a compound long used in
      traditional Chinese medicines, has been reported to have therapeutic effects in
      treating experimental colitis. In this study, we show that BBR had a protective
      effect on mice with TNBS-induced colitis. BBR inhibited levels of IFN-gamma, IL
      17, IL-6, IL-1beta and TNF-alpha both in the local colon and sera, and
      transiently increased levels of IL-22. BBR also markedly increased sIgA
      expression in the colon. BBR had pronounced effects on macrophage populations.
      Treatment with BBR adjusted the M2/M1 ratio. In addition, BBR exerted effects on
      adaptive immunity by suppressing numbers of Th1 and Th17 cells, as well as
      expression levels of their associated cytokines and transcriptional factors. BBR
      downregulated STAT3 and STAT1 phosphorylation, and inhibited phosphorylation of
      NF-kB. In vitro experiments showed that BBR inhibited the differentiation of Th17
      and, to a lesser degree, Th1 cells, without affecting regulatory T cells.
      Therefore, we conclude that BBR plays a regulatory role in modulating the balance
      of immune responses in TNBS-induced colitis. Our study will help us understand
      the regulatory mechanisms exerted by BBR in the treatment of IBD. 

PMID- 26224048
TI  - Dietary Sodium Consumption Predicts Future Blood Pressure and Incident
      Hypertension in the Japanese Normotensive General Population.
AB  - BACKGROUND: Although there is a close relationship between dietary sodium and
      hypertension, the concept that persons with relatively high dietary sodium are at
      increased risk of developing hypertension compared with those with relatively low
      dietary sodium has not been studied intensively in a cohort. METHODS AND RESULTS:
      We conducted an observational study to investigate whether dietary sodium intake
      predicts future blood pressure and the onset of hypertension in the general
      population. Individual sodium intake was estimated by calculating 24-hour urinary
      sodium excretion from spot urine in 4523 normotensive participants who visited
      our hospital for a health checkup. After a baseline examination, they were
      followed for a median of 1143 days, with the end point being development of
      hypertension. During the follow-up period, hypertension developed in 1027
      participants (22.7%). The risk of developing hypertension was higher in those
      with higher rather than lower sodium intake (hazard ratio 1.25, 95% CI 1.04 to
      1.50). In multivariate Cox proportional hazards regression analysis, baseline
      sodium intake and the yearly change in sodium intake during the follow-up period
      (as continuous variables) correlated with the incidence of hypertension.
      Furthermore, both the yearly increase in sodium intake and baseline sodium intake
      showed significant correlations with the yearly increase in systolic blood
      pressure in multivariate regression analysis after adjustment for possible risk
      factors. CONCLUSIONS: Both relatively high levels of dietary sodium intake and
      gradual increases in dietary sodium are associated with future increases in blood
      pressure and the incidence of hypertension in the Japanese general population.

PMID- 26224049
TI  - Hypothyroidism Is Associated With Coronary Endothelial Dysfunction in Women.
AB  - BACKGROUND: Hypothyroidism is associated with an increased risk of coronary
      artery disease, beyond that which can be explained by its association with
      conventional cardiovascular risk factors. Coronary endothelial dysfunction
      precedes atherosclerosis, has been linked to adverse cardiovascular events, and
      may account for some of the increased risk in patients with hypothyroidism. The
      aim of this study was to determine whether there is an association between
      epicardial and microvascular coronary endothelial dysfunction and hypothyroidism.
      METHODS AND RESULTS: In 1388 patients (mean age 50.5 [12.3] years, 34% male)
      presenting with stable chest pain to Mayo Clinic, Rochester, MN for diagnostic
      coronary angiography, and who were found to have nonobstructive coronary artery
      disease (<40% stenosis), we invasively assessed coronary artery endothelial
      dependent microvascular and epicardial function by evaluating changes in coronary
      blood flow (% Delta CBF Ach) and diameter (% Delta CAD Ach), respectively, in
      response to intracoronary infusions of acetylcholine. Patients were divided into
      2 groups: hypothyroidism, defined as a documented history of hypothyroidism or a
      thyroid-stimulating hormone (TSH) >10.0 mU/mL, n=188, and euthyroidism, defined
      as an absence of a history of hypothyroidism in the clinical record and/or
      0.3<TSH<=10.0 mU/mL, n=1200. Subjects with a history of hypothyroidism had a
      significantly lower % Delta CBF Ach (48.26 [80.66] versus 64.58 [128.30])
      compared to patients with euthyroidism, while the % Delta CAD Ach did not vary
      significantly between groups. After adjusting for covariates, females with
      hypothyroidism still had a significantly lower % Delta CBF Ach (estimated
      difference in % Delta CBF Ach [SE]: -16.79 [8.18]). CONCLUSIONS: Hypothyroidism
      in women is associated with microvascular endothelial dysfunction, even after
      adjusting for confounders, and may explain some of the increased risk of
      cardiovascular disease in these patients.

PMID- 26224050
TI  - Semimechanistic model describing gastric emptying and glucose absorption in
      healthy subjects and patients with type 2 diabetes.
AB  - The integrated glucose-insulin (IGI) model is a previously published
      semimechanistic model that describes plasma glucose and insulin concentrations
      after glucose challenges. The aim of this work was to use knowledge of physiology
      to improve the IGI model's description of glucose absorption and gastric emptying
      after tests with varying glucose doses. The developed model's performance was
      compared to empirical models. To develop our model, data from oral and
      intravenous glucose challenges in patients with type 2 diabetes and healthy
      control subjects were used together with present knowledge of small intestinal
      transit time, glucose inhibition of gastric emptying, and saturable absorption of
      glucose over the epithelium to improve the description of gastric emptying and
      glucose absorption in the IGI model. Duodenal glucose was found to inhibit
      gastric emptying. The performance of the saturable glucose absorption was
      superior to linear absorption regardless of the gastric emptying model applied.
      The semiphysiological model developed performed better than previously published
      empirical models and allows better understanding of the mechanisms underlying
      glucose absorption. In conclusion, our new model provides a better description
      and improves the understanding of dynamic glucose tests involving oral glucose. 

PMID- 26224052
TI  - Marked alterations of neutrophil functions during sepsis-induced
      immunosuppression.
AB  - Severe septic syndromes deeply impair innate and adaptive immunity and are
      responsible for sepsis-induced immunosuppression. Although neutrophils represent
      the first line of defense against infection, little is known about their
      phenotype and functions a few days after sepsis, when the immunosuppressive phase
      is maximal (i.e., between d 3 and 8). The objective of the present study was to
      perform, for the first time, a global evaluation of neutrophil alterations in
      immunosuppressed septic patients (at d 3-4 and d 6-8) using phenotypic and
      functional studies. In addition, the potential association of these parameters
      and deleterious outcomes was assessed. Peripheral blood was collected from 43
      septic shock patients and compared with that of 23 healthy controls. In the
      septic patients, our results highlight a markedly altered neutrophil chemotaxis
      (functional and chemokine receptor expressions), oxidative burst, and lactoferrin
      content and an increased number of circulating immature granulocytes (i.e.,
      CD10(dim)CD16(dim)). These aspects were associated with an increased risk of
      death after septic shock. In contrast, phagocytosis and activation capacities
      were conserved. To conclude, circulating neutrophils present with phenotypic,
      functional, and morphologic alterations a few days after sepsis onset. These
      dysfunctions might participate in the deleterious role of sepsis-induced
      immunosuppression. The present results open new perspectives in the mechanisms
      favoring nosocomial infections after septic shock. They deserve to be further
      investigated in a larger clinical study and in animal models recapitulating these
      alterations. 

PMID- 26224053
TI  - Reply: Reversible cerebral vasoconstriction syndrome might account for the
      headaches simulating subarachnoid haemorrhage.

PMID- 26224054
TI  - Reply: A unique manifestation of primary adrenal insufficiency or a miss after
      all?

PMID- 26224055
TI  - Lynch syndrome in the 21st century: clinical perspectives.
AB  - Lynch syndrome (LS) is the most common of all inherited cancer syndromes,
      associated with substantially elevated risks for colonic and extracolonic
      malignancies, earlier onset and high rates of multiple primary cancers. At the
      genetic level, it is caused by a defective mismatch repair (MMR) system due to
      presence of germline defects in at least one of the MMR genes- MLH1, MSH2, MSH6,
      PMS2 or EPCAM. An impaired MMR function during replication introduces infidelity
      in DNA sequence and leads to ubiquitous mutations at simple repetitive sequences
      (microsatellites), causing microsatellite instability (MSI). Although previously,
      clinicopathological criteria such as Amsterdam I/II and Revised Bethesda
      Guidelines were commonly used to identify suspected LS mutation carriers, there
      has been a recent push towards universally testing, especially in case of
      colorectal cancers (CRCs), through immunohistochemistry for expression of MMR
      proteins or through molecular tests (polymerase chain reaction, PCR) for MSI, in
      order to identify LS mutation carriers and subject them to genetic testing to
      ascertain the specific gene implicated. In this review, we have discussed the
      latest diagnostic strategies and the current screening and treatment guidelines
      for colonic and extracolonic cancers in clinically affected and at-risk
      individuals for LS. 

PMID- 26224056
TI  - A unique manifestation of primary adrenal insufficiency or a miss after all?

PMID- 26224057
TI  - Resting-state functional brain networks in Parkinson's disease.
AB  - The network approach is increasingly being applied to the investigation of normal
      brain function and its impairment. In the present review, we introduce the main
      methodological approaches employed for the analysis of resting-state neuroimaging
      data in Parkinson's disease studies. We then summarize the results of recent
      studies that used a functional network perspective to evaluate the changes
      underlying different manifestations of Parkinson's disease, with an emphasis on
      its cognitive symptoms. Despite the variability reported by many studies, these
      methods show promise as tools for shedding light on the pathophysiological
      substrates of different aspects of Parkinson's disease, as well as for
      differential diagnosis, treatment monitoring and establishment of imaging
      biomarkers for more severe clinical outcomes. 

PMID- 26224059
TI  - Recanalisation and ulcer recurrence rates following ultrasound-guided foam
      sclerotherapy.
AB  - OBJECTIVES: The aim was to assess vein recanalisation and ulcer recurrence in
      patients with chronic venous ulceration following ultrasound-guided foam
      sclerotherapy. METHOD: Open (CEAP 6) or recently healed (CEAP 5) chronic venous
      leg ulcers were treated with foam sclerotherapy between July 2010 and August
      2012. Venous duplex scans were performed two weeks and one and two years post
      treatment, recording recanalisation and reflux. One- and two-year ulcer
      recurrence rates were calculated using Kaplan-Meier survival analysis. RESULTS: A
      total of 100 legs were treated in 92 patients; 86 were CEAP 5 and 14 were CEAP 6.
      At two weeks complete or short segment occlusion was demonstrated in 99/100 legs.
      Complete follow-up was 93% at one year and 88% at two years. Complete and
      segmental recanalisation with new reflux was recorded in 11/93 (12%) legs and
      25/93 (27%) legs, respectively (overall 36/93; 39%) at one year; and 6/88 (7%)
      legs and 15/88 (17%) legs, respectively (overall 21/88; 24%) at two years. Kaplan
      Meier survival analysis shows 64% ulcers healed at 24 weeks and 86% at one year.
      Ulcer recurrence rate at one and two years was 2.3% and 5.1%. CONCLUSIONS: Over
      one-third of superficial veins treated with foam sclerotherapy recanalised at one
      year and just under a quarter of superficial veins recanalised at two years.
      Despite this, ulcer recurrence rates were low, and recanalisation failed to
      predict recurrence.

PMID- 26224058
TI  - Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation
      in opposite directions.
AB  - Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the
      bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and
      large subunit, respectively, impacts translation by controlling intersubunit
      rotation. Here we show that aminoglycosides chemically related to neomycin
      paromomycin, ribostamycin and neamine-each bind to sites within h44 and H69 to
      perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which
      only differ by their ring-I 6'-polar group, drive subunit rotation in opposite
      directions. This suggests that their distinct actions hinge on the 6'-substituent
      and the drug's net positive charge. By solving the crystal structure of the
      paromomycin-ribosome complex, we observe specific contacts between the apical tip
      of H69 and the 6'-hydroxyl on paromomycin from within the drug's canonical h44
      binding site. These results indicate that aminoglycoside actions must be framed
      in the context of bridge B2 and their regulation of subunit rotation. 

PMID- 26224061
TI  - Lifetime risk of being diagnosed with, or dying from, prostate cancer by major
      ethnic group in England 2008-2010.
AB  - BACKGROUND: In the UK, a man's lifetime risk of being diagnosed with prostate
      cancer is 1 in 8. We calculated both the lifetime risk of being diagnosed with
      and dying from prostate cancer by major ethnic group. METHODS: Public Health
      England provided prostate cancer incidence and mortality data for England (2008
      2010) by major ethnic group. Ethnicity and mortality data were incomplete,
      requiring various assumptions and adjustments before lifetime risk was calculated
      using DevCan (percent, range). RESULTS: The lifetime risk of being diagnosed with
      prostate cancer is approximately 1 in 8 (13.3 %, 13.2-15.0 %) for White men, 1 in
      4 (29.3 %, 23.5-37.2 %) for Black men, and 1 in 13 (7.9 %, 6.3-10.5 %) for Asian
      men, whereas that of dying from prostate cancer is approximately 1 in 24 (4.2 %,
      4.2-4.7 %) for White men, 1 in 12 (8.7 %, 7.6-10.6 %) for Black men, and 1 in 44
      (2.3 %, 1.9-3.0 %) for Asian men. CONCLUSIONS: In England, Black men are at twice
      the risk of being diagnosed with, and dying from, prostate cancer compared to
      White men. This is an important message to communicate to Black men. White,
      Black, and Asian men with a prostate cancer diagnosis are all as likely to die
      from the disease, independent of their ethnicity. Nonetheless, proportionally
      more Black men are dying from prostate cancer in England.

PMID- 26224062
TI  - Socioeconomic factors and other sources of variation in the prevalence of genital
      chlamydia infections: A systematic review and meta-analysis.
AB  - BACKGROUND: The success of chlamydia screening programmes relies on their ability
      to effectively target those with greatest need. Young people from disadvantaged
      backgrounds may be at greater need for chlamydia screening, but existing evidence
      on the variation of prevalence with social position is inconclusive. We carried
      out a systematic review to examine variation in chlamydia prevalence in
      populations and possible sources of this variation. METHODS: Studies were
      eligible if they reported chlamydia prevalence derived from population-based
      samples that included young people aged 15-24 years from Europe, North America or
      Australia. Systematic searches of the following databases were undertaken from
      their inception to November 2014: MEDLINE, Embase, Web of Science and PsychINFO.
      There were no restrictions by language or publication date. Independent screening
      for eligibility and data extraction were carried out by two reviewers. Where
      possible, data were pooled in a meta-analysis using a random effects model.
      Heterogeneity was further investigated using meta-regression techniques. RESULTS:
      Of 1248 unique titles and abstracts and 263 potentially relevant full texts, 29
      studies were eligible for inclusion. There was relatively strong evidence that
      disadvantaged young people had an increased risk of having a chlamydia infection
      across multiple measures of disadvantage, including lower educational attainment
      (OR 1.94, 95% CI: 1.52 to 2.47), lower occupational class (OR 1.49, 95% CI: 1.07
      to 2.08) and residence in deprived areas (OR 1.76, 95% CI: 1.15 to 2.71) with an
      overall OR of 1.66 (95% CI: 1.37 to 2.02). Socioeconomic disadvantage was
      associated with chlamydia infection in both men and women. There was weaker
      evidence that prevalence estimates also varied by gender and age. CONCLUSIONS:
      This review provides evidence of a consistent association between socioeconomic
      disadvantage and higher risk of Chlamydia infection. This association may reflect
      a number of factors including social variation in engagement with Chlamydia
      control programmes. Chlamydia screening could therefore reduce or increase health
      inequalities, depending on service provision and uptake by different
      socioeconomic groups.

PMID- 26224063
TI  - Implementation of the ABL-90 blood gas analyzer in a ground-based mobile
      emergency care unit.
AB  - Point-of Care analysis is increasingly being applied in the prehospital scene.
      Arterial blood gas analysis is one of many new initiatives adding to the
      diagnostic tools of the prehospital physician. In this paper we present a study
      on the feasibility of the Radiometer ABL-90 in a ground-based Mobile Emergency
      Care Unit and report on some clinical situations in which the apparatus has
      proven beneficial. 

PMID- 26224064
TI  - Assessing the structure of non-routine decision processes in Airline Operations
      Control.
AB  - Unfamiliar severe disruptions challenge Airline Operations Control professionals
      most, as their expertise is stretched to its limits. This study has elicited the
      structure of Airline Operations Control professionals' decision process during
      unfamiliar disruptions by mapping three macrocognitive activities on the decision
      ladder: sensemaking, option evaluation and action planning. The relationship
      between this structure and decision quality was measured. A simulated task was
      staged, based on which think-aloud protocols were obtained. Results show that the
      general decision process structure resembles the structure of experts working
      under routine conditions, in terms of the general structure of the macrocognitive
      activities, and the rule-based approach used to identify options and actions.
      Surprisingly, high quality of decision outcomes was found to relate to the use of
      rule-based strategies. This implies that successful professionals are capable of
      dealing with unfamiliar problems by reframing them into familiar ones, rather
      than to engage in knowledge-based processing. Practitioner Summary: We examined
      the macrocognitive structure of Airline Operations Control professionals'
      decision process during a simulated unfamiliar disruption in relation to decision
      quality. Results suggest that successful professionals are capable of dealing
      with unfamiliar problems by reframing them into familiar ones, rather than to
      engage in knowledge-based processing. 

PMID- 26224065
TI  - Reported health related headlines are often unhelpful.

PMID- 26224066
TI  - Disinhibition-induced transitions between absence and tonic-clonic epileptic
      seizures.
AB  - Electrophysiological experiments have long revealed the existence of two-way
      transitions between absence and tonic-clonic epileptic seizures in the cerebral
      cortex. Based on a modified spatially-extended Taylor &Baier neural field model,
      we here propose a computational framework to mathematically describe the
      transition dynamics between these epileptic seizures. We first demonstrate the
      existence of various transition types that are induced by disinhibitory functions
      between two inhibitory variables in an isolated Taylor &Baier model. Moreover, we
      show that these disinhibition-induced transitions can lead to stable tonic-clonic
      oscillations as well as periodic spike with slow-wave discharges, which are the
      hallmark of absence seizures. We also observe fascinating dynamical states, such
      as periodic 2-spike with slow-wave discharges, tonic death, bursting
      oscillations, as well as saturated firing. Most importantly, we identify paths
      that represent physiologically plausible transitions between absence and tonic
      clonic seizures in the modified spatially-extended Taylor &Baier model. 

PMID- 26224067
TI  - Dairy and nondairy beverage consumption for childhood atopic eczema: what health
      advice to give?
AB  - BACKGROUND: Many parents of children with atopic eczema (AE) practise empirical
      dietary avoidance and supplementation, and seek healthcare advice on whether
      consumption of dairy and nondairy beverages may be beneficial or detrimental for
      this condition. AIM: We investigated if frequency of consumption of beverages was
      associated with disease severity and quality of life (QoL). METHODS: Parent
      reported frequency of drinks and beverages were recorded in consecutive children
      with AE, and disease severity (Nottingham Eczema Severity Score; NESS), QoL
      (Children's Dermatology Life Quality Index; CDLQI), skin hydration (SH),
      transepidermal water loss (TEWL), blood pressure (BP), resting heart rate (RHR)
      and body mass index (BMI) were evaluated. RESULTS: AE was associated with worse
      QoL than miscellaneous non-AE skin diseases (P < 0.001). Compared with children
      without AE, there was a trend for children with AE to drink less milk (P = 0.06)
      and more miscellaneous beverages (such as Chinese herbal tea and soymilk; P =
      0.03). In children with AE, NESS correlated with CDLQI (rho = 0.66, P < 0.001)
      and reduced SH (rho = -0.32, P < 0.001), whereas CDLQI correlated with a higher
      RHR (rho = 0.25, P < 0.01). Multiple logistic regression showed that male sex (OR
      = 0.44, 95% CI 0.20-0.97; P = 0.04) and drinking fresh milk (OR = 0.42, 95% CI
      0.20-0.93; P = 0.03) were independent factors associated with less severe
      disease. Moderate to severe impairment of CDLQI was associated with NESS (OR =
      1.48, 95% CI 1.28-1.71; P < 0.001) and RHR (OR = 1.05, 95% CI 1.02-1.08; P <
      0.01) but not with reported habits of beverage consumption. Concerning
      cardiovascular health in AE, frequency of formula milk consumption was associated
      with RHR (rho = 0.17, P = 0.04), and soft drink consumption was associated with
      higher systolic blood pressure (SBP) (rho = 0.18, P = 0.04). CONCLUSION: This
      study provides evidence for parental/patient guidance. Children with AE who
      reported more fresh milk consumption had less severe disease. There was no
      correlation between consumption of nondairy beverages with disease severity or
      QoL, but frequency of soft drink consumption correlated with SBP. With these
      results being supported by a literature review, it is reasonable to advise
      parents that fresh milk can be consumed by unsensitized children with AE. Soft
      drinks and other beverages should not be consumed in excess for optimal
      cardiovascular health and for other health reasons.

PMID- 26224068
TI  - HMGB1 promotes the activation of NLRP3 and caspase-8 inflammasomes via NF-kappaB
      pathway in acute glaucoma.
AB  - BACKGROUND: Acute glaucoma is a significantly sight-threatening cause of
      irreversible blindness in the world characterized by a sudden and substantial
      intraocular pressure (IOP) increase and subsequent retinal ganglion cell (RGC)
      death. This study aims to explore the role of high-mobility group box 1 (HMGB1)
      in an acute glaucoma mouse model. METHODS: An acute glaucoma model was induced by
      a rapid and substantial increase IOP to 70 mmHg for 60 min via anterior chamber
      punctured and affused with Balance Salt Solution in C57BL/6 mice. Retinal tissue
      ischemic damage and loss of RGCs were assessed at 6, 24, 48, 72 h after high IOP
      treatment, and at 48 h, group with or without recombinant high-mobility group box
      1 (rHMGB1), the HMGB1 inhibitor, glycyrrhizic acid (GA), and by HE and
      immunofluorescent staining. The nuclear factor kappaB (NF-kappaB) inhibitor, JSH
      23, and caspase-8 inhibitor, Z-IETD-fmk, were injected into vitreous. Reverse
      transcription and semi-quantitative reverse transcription polymerase chain
      reaction (RT-PCR), western blotting, and immunoprecipitation were performed to
      evaluate the expression level of nucleotide-binding domain, leucine-rich repeat
      containing protein 3 (NLRP3), phosphor-NF-kappaB p65, caspase-8, caspase-1,
      apoptosis-associated speck-like protein containing a CARD (ASC), and interleukin
      1beta (IL-1beta). RESULTS: HMGB1 was increased in ischemic retinal tissue during
      acute glaucoma as early as 6 h after rapid IOP elevation. Exogenous HMGB1
      exacerbated retinal ischemic damage, RGC loss, and inhibition of endogenous HMGB1
      significantly reduced the severity of disease. HMGB1 significantly induced the
      elevation of canonical NLRP3, ASC, caspase-1, and non-canonical capase-8-ASC
      inflammasome and promoted the processing of IL-1beta. Furthermore, the effect of
      HMGB1 on NLRP3 inflammasome activation and IL-1beta production was dependent on
      NF-kappaB pathway. Thus, HMGB1/caspase-8 pathway promoted the processing of IL
      1beta via NF-kappaB pathway. CONCLUSION: The findings of this study identified a
      novel signaling pathway in which HMGB1, in response to acutely elevated
      intraocular pressure, activated the canonical NLRP3 and non-canonical caspase-8
      inflammasomes and production of IL-1beta during acute glaucoma development. These
      results provide new insights to the understanding of the innate response that
      contributes to pathogenesis of acute glaucoma.

PMID- 26224069
TI  - Early statin use in ischemic stroke patients treated with recanalization therapy:
      retrospective observational study.
AB  - BACKGROUND: We aimed to determine whether early statin use following
      recanalization therapy improves the functional outcome of ischemic stroke.
      METHODS: Using a prospective stroke registry database, we identified a
      consecutive 337 patients within 6 h of onset who had symptomatic stenosis or
      occlusion of major cerebral arteries and received recanalization therapy. Based
      on commencement of statin therapy, patients were categorized into administration
      on the first (D1, 13.4%), second (D2, 20.8%) and third day or later (D >= 3,
      15.4%) after recanalization therapy, and no use (NU, 50.4%). The primary efficacy
      outcome was a 3-month modified Rankin Scale score of 0-1, and the secondary
      outcomes were neurologic improvement, neurologic deterioration and symptomatic
      hemorrhagic transformation during hospitalization. RESULTS: Earlier use of statin
      was associated with a better primary outcome in a dose-response relationship (P
      for trend = 0.01) independent of premorbid statin use, stroke history, atrial
      fibrillation, stroke subtype, calendar year, and methods of recanalization
      therapy. The odds of a better primary outcome increased in D1 compared to NU
      (adjusted odds ratio, 2.96; 95% confidence interval, 1.19-7.37). Earlier statin
      use was significantly associated with less neurologic deterioration and
      symptomatic hemorrhagic transformation in bivariate analyses but not in
      multivariable analyses. Interaction analysis revealed that the effect of early
      statin use was not altered by stroke subtype and recanalization modality (P for
      interaction = 0.97 and 0.26, respectively). CONCLUSION: Early statin use after
      recanalization therapy in ischemic stroke may improve the likelihood of a better
      functional outcome without increasing the risk of intracranial hemorrhage.

PMID- 26224070
TI  - Double robust and efficient estimation of a prognostic model for events in the
      presence of dependent censoring.
AB  - In longitudinal data arising from observational or experimental studies,
      dependent subject drop-out is a common occurrence. If the goal is estimation of
      the parameters of a marginal complete-data model for the outcome, biased
      inference will result from fitting the model of interest with only uncensored
      subjects. For example, investigators are interested in estimating a prognostic
      model for clinical events in HIV-positive patients, under the counterfactual
      scenario in which everyone remained on ART (when in reality, only a subset had).
      Inverse probability of censoring weighting (IPCW) is a popular method that relies
      on correct estimation of the probability of censoring to produce consistent
      estimation, but is an inefficient estimator in its standard form. We introduce
      sequentially augmented regression (SAR), an adaptation of the Bang and Robins
      (2005. Doubly robust estimation in missing data and causal inference models.
      Biometrics 61, 962-972.) method to estimate a complete-data prediction model,
      adjusting for longitudinal missing at random censoring. In addition, we propose a
      closely related non-parametric approach using targeted maximum likelihood
      estimation (TMLE; van der Laan and Rubin, 2006. Targeted maximum likelihood
      learning. The International Journal of Biostatistics 2 (1), Article 11). We
      compare IPCW, SAR, and TMLE (implemented parametrically and with Super Learner)
      through simulation and the above-mentioned case study.

PMID- 26224071
TI  - Cohort Profile: The Rotterdam Periconceptional Cohort (Predict Study).

PMID- 26224072
TI  - Long-term cardiac prognosis and risk stratification in 260 adults presenting with
      mitochondrial diseases.
AB  - AIMS: The aim of this study is to assess the long-term cardiac prognosis of
      adults with mitochondrial diseases. METHODS AND RESULTS: Between January 2000 and
      May 2014, we retrospectively included in this study 260 consecutive patients (60%
      women) >=18 years (interquartile range 31-54), with genetically proven
      mitochondrial diseases, including 109 with mitochondrial DNA (mtDNA) single large
      scale deletions, 64 with the m.3243A>G mutation in MT-TL1, 51 with other mtDNA
      point mutations, and 36 patients with nuclear gene mutations. Cardiac involvement
      was present at baseline in 81 patients (30%). Single and multiple variable
      analyses were performed in search of predictors of major adverse cardiac events
      (MACEs), and hazard ratios (HRs) and 95% confidence intervals (CI) were
      calculated. Over a median follow-up of 7 years (3.6-11.7), 27 patients (10%)
      suffered a MACE, defined as sudden death, death due to heart failure (HF),
      resuscitated cardiac arrest, third-degree atrioventricular block, sinus node
      dysfunction, cardiac transplantation, or hospitalization for management of HF.
      Patients with single large-scale mtDNA deletions or m.3243A>G mutations had the
      highest incidence of MACE. By multiple variable analysis, intraventricular
      conduction block (HR = 16.9; 95% CI: 7.2-39.4), diabetes (HR = 7.0; 95% CI: 2.9
      16.7), premature ventricular complexes (HR = 3.6; 95% CI: 1.4-9.2), and left
      ventricular (LV) hypertrophy (HR = 2.5; 95% CI: 1.1-5.8) were independent
      predictors of MACEs. In patients with zero, one, and two or more risk factors,
      the incidences of MACE were 1.7, 15 and 42%, respectively. CONCLUSION: Patients
      with mitochondrial diseases are at high risk of MACE, independently predicted by
      intraventricular conduction block, diabetes, ventricular prematurity, and LV
      hypertrophy.

PMID- 26224073
TI  - Unveiling wild-type transthyretin cardiac amyloidosis as a significant and
      potentially modifiable cause of heart failure with preserved ejection fraction.

PMID- 26224074
TI  - Unusual echocardiographic image of a left circumflex coronary artery with
      anomalous origin from the right coronary sinus.

PMID- 26224075
TI  - Ghrelin restores nitric oxide availability in resistance circulation of essential
      hypertensive patients: role of NAD(P)H oxidase.
AB  - AIMS: We assessed whether acute intra-arterial infusion of exogenous ghrelin can
      improve endothelial dysfunction by restoring nitric oxide (NO) availability in
      the forearm microcirculation of essential hypertensive patients. The effect of
      ghrelin on endothelial dysfunction (pressurized myograph), vascular oxidative
      stress generation (fluorescent dihydroethidium), and phosphorylation of p47phox
      (western blot), an index of NAD(P)H oxidase activation, in isolated small
      arteries taken from essential hypertensive patients (subcutaneous biopsy) were
      also investigated. METHODS AND RESULTS: In 18 normotensive control subjects and
      18 essential hypertensive patients, we studied the forearm blood flow (strain
      gauge plethysmography) response to intra-arterial acetylcholine, repeated under
      NO synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA) or the antioxidant
      ascorbic acid. The protocol was repeated at the end of exogenous ghrelin intra
      arterial infusion. In hypertensive patients, ghrelin normalized the blunted
      response to acetylcholine, restored the inhibiting effect of l-NMMA and abrogated
      the potentiating effect of ascorbic acid on acetylcholine. In controls, ghrelin
      failed to modify these vascular responses. In hypertensive patients, ghrelin
      decreased venous levels of malondialdehyde, lipoperoxide, and interleukin-6, and
      concomitantly increased endogenous antioxidant capacity. Small vessels from
      hypertensive patients showed an enhanced intravascular oxidative stress, which
      was strongly and similarly decreased by incubation with ghrelin, the NAD(P)H
      oxidase inhibitor gp91 ds-tat, or both. Ghrelin also normalized the
      overexpression of p47 phosphorylation and restored the NO availability in small
      vessels from hypertensive patients. CONCLUSIONS: Exogenous ghrelin increases
      endothelial dysfunction by restoring NO availability in the forearm
      microcirculation of essential hypertensive patients, an effect ascribable to an
      antioxidant effect via inhibition of NAD(P)H oxidase activation.

PMID- 26224076
TI  - Wild-type transthyretin amyloidosis as a cause of heart failure with preserved
      ejection fraction.
AB  - AIMS: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous
      clinical syndrome with multiple underlying causes. Wild-type transthyretin (TTR)
      amyloidosis (ATTRwt) is an underdiagnosed cause of HFpEF that might benefit from
      new specific treatments. ATTRwt can be diagnosed non-invasively by (99m)Tc-3,3
      diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy. We sought to
      determine the prevalence of ATTRwt among elderly patients admitted due to HFpEF.
      METHODS AND RESULTS: We prospectively screened all consecutive patients >=60
      years old admitted due to HFpEF [left ventricular (LV) ejection fraction >=50%]
      with LV hypertrophy (>=12 mm). All eligible patients were offered a (99m)Tc-DPD
      scintigraphy. The study included 120 HFpEF patients (59% women, 82 +/- 8 years).
      A total of 16 patients (13.3%; 95% confidence interval: 7.2-19.5) showed a
      moderate-to-severe uptake on the (99m)Tc-DPD scintigraphy. All patients with a
      positive scan underwent genetic testing of the TTR gene, and no mutations were
      found. An endomyocardial biopsy was performed in four patients, confirming ATTRwt
      in all cases. There were no differences in age, gender, hypertension, diabetes,
      coronary artery disease, or atrial fibrillation between ATTRwt patients and
      patients with other HFpEF forms. Although patients with ATTRwt exhibited higher
      median N-terminal pro-brain natriuretic peptide (6467 vs. 3173 pg/L; P = 0.019),
      median troponin I (0.135 vs. 0.025 ug/L; P < 0.001), mean LV maximal wall
      thickness (17 +/- 3.4 vs. 14 +/- 2.5 mm; P = 0.001), rate of pericardial effusion
      (44 vs. 19%; P = 0.047), and rate of pacemakers (44 vs. 12%; P = 0.004), clinical
      overlap between ATTRwt and other HFpEF forms was high. CONCLUSION: ATTRwt is an
      underdiagnosed disease that accounts for a significant number (13%) of HFpEF
      cases. The effect of emerging TTR-modifying drugs should be evaluated in these
      patients.

PMID- 26224077
TI  - Corrigendum to: 2014 ESC Guidelines on the diagnosis and management of acute
      pulmonary embolism.

PMID- 26224078
TI  - Adolfo J. de Bold PhD OC FRSC: a pioneer  in cardiovascular medicine.
AB  - Eugene Braunwald MD discusses the discovery of the Natriuretic Peptide System by
      A J de Bold, which as a consequence, made it possible for the Federal Drug
      Administration to approve the first ARNi on 7 July 2015.

PMID- 26224079
TI  - Research ethics needs fine tuning, not rigidity: how to promote evidence in
      neglected patient populations by rethinking informed consent.

PMID- 26224080
TI  - Hypoxia Promotes the Inflammatory Response and Stemness Features in Visceral Fat
      Stem Cells From Obese Subjects.
AB  - Low-grade chronic inflammation is a salient feature of obesity and many
      associated disorders. This condition frequently occurs in central obesity and is
      connected to alterations of the visceral adipose tissue (AT) microenvironment.
      Understanding how obesity is related to inflammation may allow the development of
      therapeutics aimed at improving metabolic parameters in obese patients. To
      achieve this aim, we compared the features of two subpopulations of adipose
      derived stem cells (ASC) isolated from both subcutaneous and visceral AT of obese
      patients with the features of two subpopulations of ASC from the same isolation
      sites of non-obese individuals. In particular, the behavior of ASC of obese
      versus non-obese subjects during hypoxia, which occurs in obese AT and is an
      inducer of the inflammatory response, was evaluated. Obesity deeply influenced
      ASC from visceral AT (obV-ASC); these cells appeared to exhibit clearly
      distinguishable morphology and ultrastructure as well as reduced proliferation,
      clonogenicity and expression of stemness, differentiation and inflammation
      related genes. These cells also exhibited a deregulated response to hypoxia,
      which induced strong tissue-specific NF-kB activation and an NF-kB-mediated
      increase in inflammatory and fibrogenic responses. Moreover, obV-ASC, which
      showed a less stem-like phenotype, recovered stemness features after hypoxia. Our
      findings demonstrated the peculiar behavior of obV-ASC, their influence on the
      obese visceral AT microenvironment and the therapeutic potential of NF-kB
      inhibitors. These novel findings suggest that the deregulated hyper
      responsiveness to hypoxic stimulus of ASC from visceral AT of obese subjects may
      contribute via paracrine mechanisms to low-grade chronic inflammation, which has
      been implicated in obesity-related morbidity.

PMID- 26224081
TI  - miR-375 Modulates Radiosensitivity of HR-HPV-Positive Cervical Cancer Cells by
      Targeting UBE3A through the p53 Pathway.
AB  - BACKGROUND: Prediction of radioresistance of HR-HPV-positive (+) cervical cancer,
      especially before the course of radiotherapy, is quite beneficial to develop an
      optimal treatment strategy for individual patients. Unfortunately, the mechanisms
      responsible for radioresistance of cervical cancer are still largely unexplored.
      HR-HPV infection leads to a series of changes to normal biophysical process,
      including miRNAs expression. In this study, we explored the association between
      miR-375 and radioresistance in HR-HPV (+) cervical cancer. MATERIAL AND METHODS:
      qRT-PCR analysis was performed to determine miR-375 expression in HR-HPV-positive
      (+) cervical cancer patients and in HPV-16-positive SiHa and HPV-18-positive HeLa
      cervical cancer cell lines. The influence of miR-375 on radiosensitivity and the
      downstream regulative network were further explored in the cell line models.
      RESULTS: The results verified a putative binding site between miR-375 and UBE3A.
      miR-375 overexpression could significantly reduce UBE3A expression. UBE3A
      knockdown led to significantly reduced cell survival under radiation treatment.
      miR-375 promoted radiosensitivity of HR-HPV (+) cancer through decreasing p53
      degradation and thereby increasing radiation-induced apoptosis. CONCLUSIONS: The
      miR-375-UBE3A axis is important in modulating radiosensitivity of HR-HPV (+)
      cervical cancer.

PMID- 26224083
TI  - Mass Cytometry: A High-Throughput Platform to  Visualize the Heterogeneity of
      Acute Myeloid Leukemia.
AB  - Behbehani and colleagues use mass cytometry to profile the heterogeneity of acute
      myeloid leukemia (AML ) as compared with normal hematopoiesis. By using this
      approach and characterizing leukemic stem cells, important differences in
      response to chemotherapy between AML subsets can potentially be explained and new
      targeted approaches considered.

PMID- 26224082
TI  - Rosette Nanotubes Alter IgE-Mediated Degranulation in the Rat Basophilic Leukemia
      (RBL)-2H3 Cell Line.
AB  - In this study, the effects of rosette nanotube (RNT) exposure on immune cell
      viability and function were investigated in vitro using the rat basophilic
      leukemia (RBL)-2H3 cell line. RBL-2H3 viability was decreased in a dose- and time
      dependent manner after lysine-functionalized RNT (K-RNT) exposure. In addition, K
      RNTs had a significant effect on RBL-2H3 degranulation. When K-RNT exposure was
      concurrent with IgE sensitization, 50 and 100 mg l(-1) K-RNTs elicited a
      heightened degranulatory response compared with IgE alone. Exposure to 50 and 100
      mg l(-1) K-RNTs also caused degranulation in RBL-2H3 cells not sensitized with
      IgE (0 ng ml(-1) IgE). Furthermore, in cells preexposed to K-RNTs for 2 h and
      subsequently washed, sensitized, and stimulated with IgE, a potentiated
      degranulatory response was observed. Using confocal laser scanning microscopy and
      a fluorescein isothiocyanate (FITC)-functionalized RNT construct (termed
      FITC(1)/TBL(19)-RNT), we demonstrated a strong and direct affiliation between
      RNTs and RBL-2H3 cell membranes. We also demonstrated cellular internalization of
      RNTs after 2 h of exposure. Together, these data demonstrate that RNTs may
      affiliate with the cellular membrane of RBL-2H3 cells and can be internalized.
      These interactions can affect viability and alter the ability of these cells to
      elicit IgE-FcepsilonR mediated degranulation.

PMID- 26224084
TI  - DNA-PKcs Emerges as Master Driver of Metastasis.

PMID- 26224085
TI  - Effects of Bone Vibrator Position on Auditory Spatial Perception Tasks.
AB  - OBJECTIVE: This study assessed listeners' ability to localize spatially
      differentiated virtual audio signals delivered by bone conduction (BC) vibrators
      and circumaural air conduction (AC) headphones. BACKGROUND: Although the skull
      offers little intracranial sound wave attenuation, previous studies have
      demonstrated listeners' ability to localize auditory signals delivered by a pair
      of BC vibrators coupled to the mandibular condyle bones. The current study
      extended this research to other BC vibrator locations on the skull. METHOD: Each
      participant listened to virtual audio signals originating from 16 different
      horizontal locations using circumaural headphones or BC vibrators placed in front
      of, above, or behind the listener's ears. The listener's task was to indicate the
      signal's perceived direction of origin. RESULTS: Localization accuracy with the
      BC front and BC top positions was comparable to that with the headphones, but
      responses for the BC back position were less accurate than both the headphones
      and BC front position. CONCLUSION: This study supports the conclusion of previous
      studies that listeners can localize virtual 3D signals equally well using AC and
      BC transducers. Based on these results, it is apparent that BC devices could be
      substituted for AC headphones with little to no localization performance
      degradation. APPLICATION: BC headphones can be used when spatial auditory
      information needs to be delivered without occluding the ears. Although vibrator
      placement in front of the ears appears optimal from the localization standpoint,
      the top or back position may be acceptable from an operational standpoint or if
      the BC system is integrated into headgear.

PMID- 26224086
TI  - Cutting the vagal highway blocks one point of entry for prion-like alpha
      synuclein.

PMID- 26224087
TI  - A Versatile Approach Towards Nucleobase-Modified Aptamers.
AB  - A novel and versatile method has been developed for modular expansion of the
      chemical space of nucleic acid libraries, thus enabling the generation of
      nucleobase-modified aptamers with unprecedented recognition properties.
      Reintroduction of the modification after enzymatic replication gives broad access
      to many chemical modifications. This wide applicability, which is not limited to
      a single modification, will rapidly advance the application of in vitro selection
      approaches beyond what is currently feasible and enable the generation of
      aptamers to many targets that have so far not been addressable. 

PMID- 26224088
TI  - Validity of single item responses to short message service texts to monitor
      depression: an mHealth sub-study of the UK ACUDep trial.
AB  - BACKGROUND: An increasing number of research designs are using text messaging
      (SMS) as a means of self-reported symptom and outcome monitoring in a variety of
      long-term health conditions, including severity ratings of depressed mood. The
      validity of such a single item SMS score to measure latent depression is not
      currently known and is vital if SMS data are to inform clinical evaluation in the
      future. METHODS: A sub-set of depressed participants in the UK ACUDep trial
      submitted a single SMS text score (R-SMS-DS) between 1 and 9 on how depressed
      they felt around the same time as completing the PHQ-9 depression questionnaire
      on paper at 3 months follow-up of the trial. Exploratory categorical data factor
      analysis (EFA) was used to ascertain the alignment of R-SMS-DS scores with the
      factor structure of the PHQ-9. Any response bias with regard to age or gender was
      assessed by differential item functioning (DIF) analysis. RESULTS: Depression
      scores based on the PHQ-9 and R-SMS-DS at 3 months were available for 337
      participants (74 % female; mean age: 42 years, SD = 11.1), 213 of which completed
      the two outcomes within 6 days of each other. R-SMS-DS scores aligned with the
      underlying latent depression of the PHQ-9 (factor loading of 0.656) and in
      particular its affective rather than somatic dimension. The R-SMS-DS score was
      most strongly correlated with depressed mood (r = 0.607), feeling bad about
      oneself (r = 0.588) and anhedonia (r = 0.573). R-SMS-DS responses were invariant
      with respect to gender (p = 0.302). However, there was some evidence for age
      related response bias (p = 0.031), with older participants being more likely to
      endorse lower R-SMS-DS scores than younger ones. CONCLUSIONS: The R-SMS-DS used
      in the ACUDep trial was found to be a valid measure of latent affective
      depression with no gender related response bias. This text message item may
      therefore represent a useful assessment and monitoring tool meriting evaluation
      in further research. For future study designs we recommend the collection of
      outcome data by new health technologies in combination with gold standard
      instruments to ensure concurrent validity.

PMID- 26224089
TI  - Factors influencing full immunization coverage among 12-23 months of age children
      in Ethiopia: evidence from the national demographic and health survey in 2011.
AB  - BACKGROUND: Immunization remains one of the most important public health
      interventions to reduce child morbidity and mortality. The 2011 national
      demographic and health survey (DHS) indicated low full immunization coverage
      among children aged 12-23 months in Ethiopia. Factors contributing to the low
      coverage of immunization have been poorly understood. The aim of this study was
      to identify factors associated with full immunization coverage among children
      aged 12-23 months in Ethiopia. METHODS: This study used the 2011 Ethiopian
      demographic and health survey data. The survey was cross sectional by design and
      used a multistage cluster sampling procedure. A total of 1,927 mothers with
      children of 12-23 months of age were extracted from the children's dataset.
      Mothers' self-reported data and observations of vaccination cards were used to
      determine vaccine coverage. An adjusted odds ratio (AOR) with 95% confidence
      intervals (CI) was used to outline the independent predictors. RESULTS: The
      prevalence of fully immunized children was 24.3%. Specific vaccination coverage
      for three doses of DPT, three doses of polio, measles and BCG were 36.5%, 44.3%,
      55.7% and 66.3%, respectively. The multivariable analysis showed that sources of
      information from vaccination card [AOR 95% CI; 7.7 (5.95-10.06)], received
      postnatal check-up within two months after birth [AOR 95% CI; 1.8 (1.28-2.56)],
      women's awareness of community conversation program [AOR 95% CI; 1.9 (1.44-2.49)]
      and women in the rich wealth index [AOR 95% CI; 1.4 (1.06-1.94)] were the
      predictors of full immunization coverage. Women from Afar [AOR 95% CI; 0.07 (0.01
      0.68)], Amhara [AOR 95% CI; 0.33 (0.13-0.81)], Oromiya [AOR 95% CI; 0.15 (0.06
      0.37)], Somali [AOR 95% CI; 0.15 (0.04-0.55)] and Southern Nation and
      Nationalities People administrative regions [AOR 95% CI; 0.35 (0.14-0.87)] were
      less likely to fully vaccinate their children. CONCLUSION: The overall full
      immunization coverage in Ethiopia was considerably low as compared to the
      national target set (66%). Health service use and access to information on
      maternal and child health were found to predict full immunization coverage.
      Appropriate strategies should be devised to enhance health information and
      accessibility for full immunization coverage by addressing the variations among
      regions.

PMID- 26224090
TI  - Nutritional status of adolescents with cystic fibrosis treated at a reference
      center in the southeast region of Brazil.
AB  - BACKGROUND: Several factors can interfere with the full physical and emotional
      growth of adolescents, among them chronic diseases. The aim was to determine the
      nutritional status of adolescents and to associate it with puberty, pancreatic
      sufficiency, lung function and age range of Cystic Fibrosis (CF) diagnosis.
      METHODS: An observational, cross-sectional, retrospective and analytical study
      was conducted using the data of medical records. SETTING: Reference center in the
      northeastern region of the state of Sao Paulo - Brazil. PATIENTS: All adolescents
      with CF attended in 2010 were included. Some variables included: pancreatic
      sufficiency (steatocrit >2 %), pancreatic enzymes replacement (yes/no), pubertal
      status-Tanner criteria (prepubertal: M1/G1, pubertal: M2/G2 to M4/G4,
      postpubertal: M5/G5), age at CF diagnosis (<2 and >=2 years of age), Lung
      function, measured as a predicted forced expiratory volume in 1 s (FEV1). Main
      outcome measures Nutritional indicators: body mass index for age (BMI/A) and
      height for age (H/A) with z-score calculated with Anthro Plus software. Cut-off
      reference points: >= z-score -3 and < z-score -2 (thinness); z-score -2 and <= z
      score-z +1 (normal weight); >z-score +1 (overweight or obesity), and z-score <-2
      (low or very low H/A). The groups were compared by the Kruskal-Wallis test. Level
      of significance: p<0.05. RESULTS: Thirty adolescents. Median (min;max) age: 14.4
      (10.1;19.8) years. BMI/A and H/A z-score, respectively: early diagnosis of CF (
      0.8; -1.1) or late diagnosis of CF (-0.5;-0.8); with pancreatic insufficiency (
      0.7; -0.8) or without pancreatic insufficiency (-0.8; -0.5) and prepubertal (
      0.8; -0.7) pubertal (-0.2; -1.5) or postpubertal (-0.7; -0.5). No significant
      difference (p>0.05) was observed. Patients with and without pancreatic
      insufficiency, presented H/A borderline z-score (p=0.05). Association between H/A
      and FEV1 was borderline (p=0.05). CONCLUSIONS: Adolescents presented adequate
      nutritional status, although with slightly lower values than those of developed
      countries. FEV1 lower levels occurred more frequently in adolescents with low
      H/A.

PMID- 26224091
TI  - What do people really think of generic medicines? A systematic review and
      critical appraisal of literature on stakeholder perceptions of generic drugs.
AB  - BACKGROUND: Considerable emphasis is presently being placed on usage of generic
      medicines by governments focussed on the potential economic benefits associated
      with their use. Concurrently, there is increasing discussion in the lay media of
      perceived doubts regarding the quality and equivalence of generic medicines. The
      objective of this paper is to report the outcomes of a systematic search for peer
      reviewed, published studies that focus on physician, pharmacist and
      patient/consumer perspectives of generic medicines. METHODS: Literature published
      between January 2003 and November 2014, which is indexed in PubMed and Scopus, on
      the topic of opinions of physicians, pharmacists and patients with respect to
      generic medicines was searched, and articles within the scope of this review were
      appraised. Search keywords used included perception, opinion, attitude and view,
      along with keywords specific to each cohort. RESULTS: Following review of titles
      and abstracts to identify publications relevant to the scope, 16 papers on
      physician opinions, 11 papers on pharmacist opinions and 31 papers on
      patient/consumer opinions were included in this review. Quantitative studies (n =
      37) were the most common approach adopted by researchers, generally in the form
      of self-administered questionnaires/surveys. Qualitative methodologies (n = 15)
      were also reported, albeit in fewer cases. In all three cohorts, opinions of
      generic medicines have improved but some mistrust remains, most particularly in
      the patient group where there appears to be a strongly held belief that less
      expensive equals lower quality. Acceptance of generics appears to be higher in
      consumers with higher levels of education while patients from lower socioeconomic
      demographic groups, hence generally having lower levels of education, tend to
      have greater mistrust of generics. CONCLUSIONS: A key factor in improving
      confidence in generic products is the provision of information and education,
      particularly in the areas of equivalency, regulation and dispelling myths about
      generic medicines (such as the belief that they are counterfeits). Further, as
      patient trust in their physician often overrules their personal mistrust of
      generic medicines, enhancing the opinions of physicians regarding generics may
      have particular importance in strategies to promote usage and acceptance of
      generic medicines in the future.

PMID- 26224092
TI  - Clinicopathological features of double-hit B-cell lymphomas with MYC and BCL2,
      BCL6 or CCND1 rearrangements.
AB  - Double-hit (DH) lymphomas are B-cell lymphomas characterized by chromosomal
      rearrangements, specifically of MYC and either BCL2, BCL6 or CCND1. We reviewed
      22 cases of DH lymphomas. BCL2/MYC DH lymphomas constituted the majority of these
      DH lymphomas (17 cases; 77%), followed by BCL6/MYC (2 cases; 9%) lymphomas.
      Assessing morphological features using the 2008 World Health Organization
      classification system, 15 cases (68%) were determined to be B-cell lymphoma,
      unclassifiable with features intermediate between diffuse large B-cell lymphoma
      (DLBCL) and Burkitt lymphoma (BCLU) (10 cases; 45%), or as DLBCL (5 cases; 23%),
      and 2 cases (9%) were classified as morphologically untransformed follicular
      lymphoma. Burkitt lymphoma was rare (1 case; 5%) among DH lymphomas. Nineteen
      cases were treated with R-CHOP or a high dose chemotherapy regimen. After a
      median follow-up of 11 months, 7 patients had died, and the 1-year survival rate
      was 62.5%. High dose chemotherapy did not improve the outcome. We suggest that
      screening of genetic variations to detect DH lymphomas is required in diagnosing
      all lymphomas, even those determined morphologically to be follicular lymphoma. 

PMID- 26224093
TI  - Doctors must advocate for action on the high levels of child poverty.

PMID- 26224094
TI  - Voluntary exercise attenuates LPS-induced reductions in neurogenesis and
      increases microglia expression of a proneurogenic phenotype in aged mice.
AB  - BACKGROUND: Microglia can acquire various phenotypes of activation that mediate
      their inflammatory and neuroprotective effects. Aging causes microglia to become
      partially activated towards an inflammatory phenotype. As a result, aged animals
      display a prolonged neuroinflammatory response following an immune challenge.
      Currently unknown is whether this persistent neuroinflammation leads to greater
      reductions in hippocampal neurogenesis. Exercise has been shown to alter
      microglia activation in aged animals, but the nature of these changes has yet to
      be fully elucidated. The present study assessed whether aged mice show enhanced
      reductions in hippocampal neurogenesis following an acute immune challenge with
      lipopolysaccharide (LPS). Further, we assessed whether voluntary wheel running
      protects against the effects of LPS. METHODS: Adult (4 months) and aged (22
      months) male C57BL6/J mice were individually housed with or without a running
      wheel for a total of 9 weeks. After 5 weeks, mice received a single
      intraperitoneal LPS or saline injection in combination with four daily injections
      of bromodeoxyuridine (BrdU) to label dividing cells. Tissue was collected 4 weeks
      later and immunohistochemistry was conducted to measure new cell survival, new
      neuron numbers, and microglia activation. RESULTS: Data show that LPS reduced the
      number of new neurons in aged, but not adult, mice. These LPS-induced reductions
      in neurogenesis in the aged mice were prevented by wheel running. Further,
      exercise increased the proportion of microglia co-labeled with brain-derived
      neurotrophic factor (BDNF) in the aged. CONCLUSIONS: Collectively, findings
      indicate that voluntary wheel running may promote a neuroprotective microglia
      phenotype and protect against inflammation-induced reductions in hippocampal
      neurogenesis in the aged brain.

PMID- 26224095
TI  - Spinal cord hemorrhage in a patient with neurosarcoidosis on long-term
      corticosteroid therapy: case report.
AB  - BACKGROUND: Central nervous system bleeding is a rare complication of
      neurosarcoidosis: only 18 cases of spontaneous cerebral hematoma have been
      reported. We present the first recorded case of spinal cord hemorrhage in
      neurosarcoidosis. CASE PRESENTATION: A 48-year-old Caucasian woman had relapsing
      neurosarcoidosis for 5 years, with inflammatory spinal and cerebral lesions.
      While on 20 mg corticosteroids, she experienced subacute paraparesia with right
      leg pain. A spine MRI revealed a low thoracic hematomyelia at the T10-T11 level.
      Despite high doses of corticosteroids, her condition continued to worsen.
      Surgical evacuation of the hematoma was performed 10 days after the onset of
      bleeding, and she partially recovered. CONCLUSION: This report highlights the
      possibility of spinal cord hemorrhage secondary to sarcoid vasculitis. The
      patient improved after surgical evacuation of the intramedullary hematoma. Immuno
      modulating agents must be envisaged in severe neurosarcoidosis, to prevent
      complications.

PMID- 26224096
TI  - Neoadjuvant proton beam irradiation followed by transscleral resection of uveal
      melanoma in 106 cases.
AB  - AIMS: To describe results after neoadjuvant proton beam irradiation followed by
      transscleral resection of large uveal melanoma. METHODS: Retrospective
      interventional case series, including 106 consecutive patients. Local tumour
      control, enucleation and metastasis development were assessed with survival
      curves. Predictors of local recurrence and metastasis were investigated with log
      rank testing. RESULTS: Mean follow-up was 3.2 years. Local recurrence occurred in
      five cases with an estimated risk of 4.2% and 10.4% at 3 and 5 years after
      treatment, respectively. Enucleation was performed in 10 cases with an estimated
      risk of 9.2% and 18.4% at 3 and 5 years, respectively. Significant risk factors
      for local recurrence were not evident. Metastasis was estimated to occur in 28.4%
      at 3 years and 40.3% at 5 years, correlating with patient's age only (p=0.01).
      Seventy four patients (69.8%) underwent vitreoretinal surgery for complications
      after tumour resection. Median visual acuity (VA) was 20/50 at diagnosis and
      20/400 in the third year after treatment. VA preservation of 20/200 or better was
      achieved in 33 patients (31.1%). CONCLUSION: Neoadjuvant proton beam irradiation
      may help to prevent local recurrence after transscleral resection. Additional
      vitreoretinal surgery was frequently needed in the presented series. The majority
      of patients avoided enucleation and functional blindness.

PMID- 26224097
TI  - Arginine methyltransferases mediate an epigenetic ovarian response to
      endometriosis.
AB  - Endometriosis is associated with infertility and debilitating chronic pain.
      Abnormal epigenetic modifications in the human endometrium have recently been
      implicated in the pathogenesis of this condition. However, whether an altered
      epigenetic landscape contributes to pathological changes in the ovary is unknown.
      Using an established baboon endometriosis model, early-, and late-stage
      epigenetic changes in the ovary were investigated. Transcript profiling of key
      chromatin-modifying enzymes using pathway-focused PCR arrays on ovarian tissue
      from healthy control animals and at 3 and 15 months of endometriosis revealed
      dramatic changes in gene expression in a disease duration-dependent manner.
      Ingenuity Pathway Analysis indicated that transcripts for chromatin-remodeling
      enzymes associated with reproductive system disease and cancer development were
      abnormally regulated, most prominently the arginine methyltransferases CARM1,
      PRMT2, and PRMT8. Downregulation of CARM1 protein expression was also detected in
      the ovary, fully-grown oocytes and eutopic endometrium following 15 months of
      endometriosis. Sodium bisulfite sequencing revealed DNA hypermethylation within
      the PRMT8 promoter, suggesting that deregulated CpG methylation may play a role
      in transcriptional repression of this gene. These results demonstrate that
      endometriosis is associated with changes of epigenetic profiles in the primate
      ovary and suggest that arginine methyltransferases play a prominent role in
      mediating the ovarian response to endometriosis. Owing to the critical role of
      CARM1 in nuclear receptor-mediated transcription and maintenance of pluripotency
      in the cleavage stage embryo, our results suggest that epigenetic alterations in
      the ovary may have functional consequences for oocyte quality and the etiology of
      infertility associated with endometriosis. 

PMID- 26224098
TI  - Novel molecular mechanisms involved in hormonal regulation of lactate production
      in Sertoli cells.
AB  - The aim of the study was to analyze molecular mechanisms involved in FSH and
      basic fibroblast growth factor (bFGF) regulation of lactate production in rat
      Sertoli cells. The regulation of the availability of pyruvate, which is converted
      to lactate, could be a mechanism utilized by hormones to ensure lactate supply to
      germ cells. On one hand, the regulation of 6-phosphofructo-2-kinase/fructose-2,6
      biphosphatase (PFKFB) expression could result in increased glycolysis, while an
      increase in pyruvate availability may also result from a lower conversion to
      acetyl-CoA by negative regulation of pyruvate dehydrogenase complex (PDC)
      activity by phosphorylation. Sertoli cell cultures obtained from 20-day-old rats
      were used. Stimulation of the cultures with FSH or bFGF showed that FSH increases
      Pfkfb1 and Pfkfb3 expression while bFGF increases Pfkfb1 mRNA levels.
      Additionally, we observed that FSH-stimulated lactate production was inhibited in
      the presence of a PFKFB3 inhibitor, revealing the physiological relevance of this
      mechanism. As for the regulation of PDC, analysis of pyruvate dehydrogenase
      kinase (Pdk) expression showed that FSH increases Pdk3 and decreases Pdk4 mRNA
      levels while bFGF increases the expression of all Pdks. In addition, we showed
      that bFGF increases phosphorylated PDC levels and that bFGF-stimulated lactate
      production is partially inhibited in the presence of a PDK inhibitor. Altogether,
      these results add new information regarding novel molecular mechanisms involved
      in hormonal regulation of lactate production in Sertoli cells. Considering that
      lactate is essential for the production of energy in spermatocytes and
      spermatids, these mechanisms might be relevant in maintaining spermatogenesis and
      male fertility. 

PMID- 26224099
TI  - Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1
      diabetes.
AB  - AIMS/HYPOTHESIS: The rate of progression from islet autoimmunity to clinical type
      1 diabetes depends on the rate of beta cell destruction. The HLA-A*24 gene is
      associated with early diabetes onset, but previous studies have shown attenuated
      humoral responses to islet antigens in individuals with both recent and long
      standing type 1 diabetes carrying HLA-A*24. We aimed to establish whether HLA
      A*24 is also associated with attenuated humoral responses in individuals at high
      risk of type 1 diabetes. METHODS: We established HLA-A*24, DQ and rs9258750 (an
      HLA-A*24 tagged single-nucleotide polymorphism) genotype, as well as GAD, zinc
      transporter 8 (ZnT8), insulin, islet antigen-2 (IA-2), and IA-2beta autoantibody
      status in 373 islet cell antibody-positive first-degree relatives participating
      in the European Nicotinamide Diabetes Intervention Trial. RESULTS: Univariate
      regression analyses showed that humoral responses to GAD, ZnT8 and insulin were
      less common in relatives carrying HLA-A*24. The prevalence of GAD and ZnT8
      autoantibodies remained negatively associated with HLA-A*24 and rs9258750 after
      adjusting for age, sex, proband relationship and HLA class II genotype.
      CONCLUSIONS/INTERPRETATION: HLA-A*24 is associated with attenuated humoral
      responses in individuals at high risk of type 1 diabetes, and this may reflect a
      distinct phenotype of rapid beta cell loss.

PMID- 26224100
TI  - VAV2, a guanine nucleotide exchange factor for Rac1, regulates glucose-stimulated
      insulin secretion in pancreatic beta cells.
AB  - AIMS/HYPOTHESIS: Rho GTPases (Ras-related C3 botulinum toxin substrate 1 [Rac1]
      and cell division cycle 42 [Cdc42]) have been shown to regulate glucose
      stimulated insulin secretion (GSIS) via cytoskeletal remodelling, trafficking and
      fusion of insulin-secretory granules with the plasma membrane. GTP loading of
      these G proteins, which is facilitated by GDP/GTP exchange factors, is a
      requisite step in the regulation of downstream effector proteins. Guanine
      nucleotide exchange factor VAV2 (VAV2), a member of the Dbl family of proteins,
      has been identified as one of the GDP/GTP exchange factors for Rac1. Despite
      recent evidence on the regulatory roles of VAV2 in different cell types, roles of
      this guanine nucleotide exchange factor in the signalling events leading to GSIS
      remain undefined. Using immunological, short interfering RNA (siRNA),
      pharmacological and microscopic approaches we investigated the role of VAV2 in
      GSIS from islet beta cells. METHODS: Co-localisation of Rac1 and VAV2 was
      determined by Triton X-114 phase partition and confocal microscopy. Glucose
      induced actin remodelling was quantified by live cell imaging using the LifeAct
      GFP fluorescent biosensor. Rac1 activation was determined by G protein linked
      immunosorbent assay (G-LISA). RESULTS: Western blotting indicated that VAV2 is
      expressed in INS-1 832/13 beta cells, normal rat islets and human islets. Vav2
      siRNA markedly attenuated GSIS in INS-1 832/13 cells. Ehop-016, a newly
      discovered small molecule inhibitor of the VAV2-Rac1 interaction, or siRNA
      mediated knockdown of VAV2 markedly attenuated glucose-induced Rac1 activation
      and GSIS in INS-1 832/13 cells. Pharmacological findings were recapitulated in
      primary rat islets. A high glucose concentration promoted co-localisation of Rac1
      and VAV2. Real-time imaging in live cells indicated a significant inhibition of
      glucose-induced cortical actin remodelling by Ehop-016.
      CONCLUSIONS/INTERPRETATION: Our data provide the first evidence to implicate VAV2
      in glucose-induced Rac1 activation, actin remodelling and GSIS in pancreatic beta
      cells.

PMID- 26224101
TI  - Mechanisms through which a small protein and lipid preload improves glucose
      tolerance.
AB  - AIMS/HYPOTHESIS: Small protein or lipid preloads are able to improve glucose
      tolerance to a different extent and through different and poorly defined
      mechanisms. We aimed at quantifying the effect of a mixed protein and lipid
      preload and at evaluating the underlying mechanisms. METHODS: Volunteers with
      normal (NGT, n = 12) or impaired (IGT, n = 13) glucose tolerance and patients
      with type 2 diabetes (n = 10) underwent two OGTTs coupled to the double glucose
      tracer protocol, preceded by either 50 g of parmesan cheese, a boiled egg and 300
      ml of water, or 500 ml of water. We measured plasma glucose, insulin, C-peptide,
      glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide
      (GIP), pancreatic polypeptide (PP), NEFA and glucose tracers, and calculated
      glucose fluxes, beta cell function variables, insulin sensitivity and clearance.
      RESULTS: After the nutrient preload, the OGTT-induced rise of plasma glucose was
      lower than after water alone in each study group. This reduction-more pronounced
      across classes of glucose tolerance (NGT -32%, IGT -37%, type 2 diabetes -49%; p
      < 0.002)-was the result of different combinations of slower exogenous glucose
      rate of appearance, improved beta cell function and reduced insulin clearance, in
      this order of relevance, which were associated with an only mild stimulation of
      GIP and GLP-1. CONCLUSIONS/INTERPRETATION: After a non-glucidic nutrient preload,
      glucose tolerance improved in proportion to the degree of its baseline
      deterioration through mechanisms that appear particularly effective in type 2
      diabetes. Exploiting the physiological responses to nutrient ingestion might
      reveal, at least in the first stages of the diabetic disease, a potent tool to
      improve daily life glycaemic control. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT02342834 FUNDING: This work was supported by grants from the University of
      Pisa (Fondi di Ateneo) and by FCT grant (PIC/IC/82956/2007).

PMID- 26224102
TI  - Gut microorganisms as promising targets for the management of type 2 diabetes.
AB  - Each human intestine harbours not only hundreds of trillions of bacteria but also
      bacteriophage particles, viruses, fungi and archaea, which constitute a complex
      and dynamic ecosystem referred to as the gut microbiota. An increasing number of
      data obtained during the last 10 years have indicated changes in gut bacterial
      composition or function in type 2 diabetic patients. Analysis of this 'dysbiosis'
      enables the detection of alterations in specific bacteria, clusters of bacteria
      or bacterial functions associated with the occurrence or evolution of type 2
      diabetes; these bacteria are predominantly involved in the control of
      inflammation and energy homeostasis. Our review focuses on two key questions:
      does gut dysbiosis truly play a role in the occurrence of type 2 diabetes, and
      will recent discoveries linking the gut microbiota to host health be helpful for
      the development of novel therapeutic approaches for type 2 diabetes? Here we
      review how pharmacological, surgical and nutritional interventions for type 2
      diabetic patients may impact the gut microbiota. Experimental studies in animals
      are identifying which bacterial metabolites and components act on host immune
      homeostasis and glucose metabolism, primarily by targeting intestinal cells
      involved in endocrine and gut barrier functions. We discuss novel approaches
      (e.g. probiotics, prebiotics and faecal transfer) and the need for research and
      adequate intervention studies to evaluate the feasibility and relevance of these
      new therapies for the management of type 2 diabetes.

PMID- 26224103
TI  - Introducing a model incorporating early integration of specialist palliative
      care: A qualitative research study of staff's perspectives.
AB  - BACKGROUND: Palliative care has evolved to encompass early integration, with
      evaluation of patient and organisational outcomes. However, little is known of
      staff's experiences and adaptations when change occurs within palliative care
      services. AIM: To explore staff experiences of a transition from a service
      predominantly focused on end-of-life care to a specialist service encompassing
      early integration. DESIGN: Qualitative research incorporating interviews, focus
      groups and anonymous semi-structured questionnaires. Data were analysed using a
      comparative approach. Service activity data were also aggregated.
      SETTING/PARTICIPANTS: A total of 32 medical, nursing, allied health and
      administrative staff serving a 22-bed palliative care unit and community
      palliative service, within a large health service. RESULTS: Patients cared for
      within the new model were significantly more likely to be discharged home (7.9%
      increase, p = 0.003) and less likely to die in the inpatient unit (10.4%
      decrease, p < 0.001). While early symptom management was considered valuable,
      nurses particularly found additional skill expectations challenging, and
      perceived patients' acute care needs as detracting from emotional and end-of-life
      care demands. Staff views varied on whether they regarded the new model's faster
      paced work-life as consistent with fundamental palliative care principles. Less
      certainty about care goals, needing to prioritise care tasks, reduced shared
      support rituals and other losses could intensify stress, leading staff to develop
      personalised coping strategies. CONCLUSION: Services introducing and researching
      innovative models of palliative care need to ensure adequate preparation,
      maintenance of holistic care principles in faster work-paced contexts and assist
      staff dealing with demands associated with caring for patients at different
      stages of illness trajectories.

PMID- 26224104
TI  - The role of the practice facilitators in Ontario primary healthcare quality
      improvement.
AB  - BACKGROUND: Practice facilitation is a key component of quality improvement in
      primary healthcare. Studies have reported the effectiveness of practice
      facilitation in improving quality management and care delivery. However, little
      has been published about practice facilitators' training, facilitation
      activities, and their perceived role in quality improvement in primary
      healthcare. This study examined practice facilitators' training and the
      perceptions of the practice facilitator role in a provincial primary healthcare
      learning collaborative quality improvement initiative in Ontario, Canada. METHOD:
      Descriptive and qualitative methods were used to outline the practice facilitator
      training as well as to look into the experiences and perceptions of practice
      facilitators and primary healthcare teams regarding the practice facilitation
      role in quality improvement. Data collection included training artifacts,
      activity logs, self-reflection reports, and semi-structured interviews with
      practice facilitators and primary healthcare participants. Reflections and
      interviews were analyzed to identify the role of the practice facilitators from
      their own experience, and from the perspective of the participants. Descriptive
      statistics were used to learn about categories of facilitation activities
      undertaken and frequency of these activities. RESULTS: Sixteen practice
      facilitators and seven family healthcare teams participated in the study.
      Practice facilitators received a two-day intensive training workshop and
      continued training. Their time was spent mostly working directly with
      participating teams, continued learning and training, communications and
      administration. They served as coaches, resource providers, enablers and
      motivators. Participating teams expressed satisfaction with the practice
      facilitator role, although they had hoped this position would provide onsite and
      hands-on support in conducting activities of quality improvement at the practice
      level. CONCLUSIONS: Practice facilitators played a crucial role in the
      implementation of quality improvement in Ontario's learning collaborative
      program. The practice facilitator role is perceived to be that of a coach,
      enabler and motivator. This study suggests that the practice facilitator
      successfully supported participating teams to undertake quality improvement
      activities in primary healthcare settings.

PMID- 26224105
TI  - Genetic variation for leaf morphology, leaf structure and leaf carbon isotope
      discrimination in European populations of black poplar (Populus nigra L.).
AB  - To buffer against the high spatial and temporal heterogeneity of the riparian
      habitat, riparian tree species, such as black poplar (Populus nigra L.), may
      display a high level of genetic variation and phenotypic plasticity for
      functional traits. Using a multisite common garden experiment, we estimated the
      relative contribution of genetic and environmental effects on the phenotypic
      variation expressed for individual leaf area, leaf shape, leaf structure and leaf
      carbon isotope discrimination (Delta(13)C) in natural populations of black
      poplar. Twenty-four to 62 genotypes were sampled in nine metapopulations covering
      a latitudinal range from 48  degrees N to 42  degrees N in France and in Italy
      and grown in two common gardens at Orleans (ORL) and at Savigliano (SAV). In the
      two common gardens, substantial genetic variation was expressed for leaf traits
      within all metapopulations, but its expression was modulated by the environment,
      as attested by the genotype * environment (G * E) interaction variance being
      comparable to or even greater than genetic effects. For LA, G * E interactions
      were explained by both changes in genotype ranking between common gardens and
      increased variation in SAV, while these interactions were mainly attributed to
      changes in genotype ranking for Delta(13)C. The nine P. nigra metapopulations
      were highly differentiated for LA, as attested by the high coefficient of genetic
      differentiation (QST = 0.50 at ORL and 0.51 at SAV), and the pattern of
      metapopulation differentiation was highly conserved between the two common
      gardens. In contrast, they were moderately differentiated for Delta(13)C (QST =
      0.24 at ORL and 0.25 at SAV) and the metapopulation clustering changed
      significantly between common gardens. Our results evidenced that the nine P.
      nigra metapopulations present substantial genetic variation and phenotypic
      plasticity for leaf traits, which both represent potentially significant
      determinants of populations' capacities to respond, on a short-term basis and
      over generations, to environmental variations.

PMID- 26224106
TI  - Aromatic Stabilization and Hybridization Trends in Photoelectron Imaging of
      Heterocyclic Radicals and Anions.
AB  - We examine the photoelectron spectra and laboratory-frame angular distributions
      in the photodetachment of furanide (C4H3O(-)), thiophenide (C4H3S(-)), and
      thiazolide (C3H2NS(-)) and compare the results to the previously reported studies
      of pyridinide (C5H4N(-)) and oxazolide (C3H2NO(-)). Using the mixed s-p model for
      the angular distributions, the results are interpreted in terms of the effective
      fractional p character of the highest-occupied molecular orbitals of these
      heterocyclic anions, revealing trends related to the aromaticity. We conclude
      that aromatic stabilization across a series of systems may be tracked using the
      photoelectron angular distributions. In addition, we report an improved (higher
      precision) electron affinity (EA) for the thiophenyl radical, EA((*)C4H3S) =
      2.089(8) eV. The EA of thiazolyl falls within the 2.5(1) eV range, but it is not
      clear if this determination corresponds to the 2- or 5-cyclic species or the 2
      ring-open isomer. These results are analyzed in conjunction with the properties
      of other heterocyclic radicals (pyridinyl, furanyl, and oxazolyl) and interpreted
      in terms of the C-H bond dissociation energies (BDEs) of the corresponding closed
      shell molecules. The BDEs of all five-membered-ring heterocyclics studied fall
      within the 116-120 kcal/mol range, contrasting the lower BDE = 110.4(2.0)
      kcal/mol of the more aromatic six-membered-ring pyridine. The observed
      aromaticity trends are consistent with the findings derived from the anion
      photoelectron angular distributions. 

PMID- 26224107
TI  - Polymorphism of JY-1 gene is not associated with reproductive traits in goats.
AB  - Reproductive traits show either low to moderate heritability and are measured
      late in life. Thus molecular markers are required to improve the pace of genetic
      gain in these traits of economic value. Recent publications report the
      association of polymorphism in JY-1 gene with cattle reproductive traits. In this
      study, the only known single nucleotide polymorphism (C15329T) of caprine JY-1
      gene was explored for its association with reproductive traits; age at first
      heat, age at first service and age at first kidding. Black Bengal (n = 70), a
      sexually precocious and prolific goat breed of India was genotyped for the SNP by
      designing PCR-RFLP. Effect of year of birth and genotype was found to be non
      significant at 1% for all three traits. However, the effect of season of birth
      was highly significant (p <= 0.01) on age at first kidding. Polymorphism in 3'UTR
      of the JY-1 gene is not associated with the reproductive traits of goats. In
      future, studies involving large number of animals from different goat breeds as
      well as investigation of other regions of this gene would be exciting to perform.

PMID- 26224108
TI  - MR enterography under the age of 10 years: a single institutional experience.
AB  - BACKGROUND: MR enterography (MRE) plays a major role in the imaging of pediatric
      patients with inflammatory bowel disease (IBD) but can be challenging to perform
      in young children. OBJECTIVE: To review our institutional experience regarding
      the performance of MRE in children younger than 10 years of age, including the
      use of general anesthesia (GA). MATERIALS AND METHODS: Institutional review board
      approval was obtained. Radiology and anesthesia records were searched to identify
      MRE exams in children younger than 10 years old between June 2009 and May 2013.
      The following information was documented: demographics, indications for MRE, use
      of GA, imaging diagnoses, and documented GA-related side effects or adverse
      events. Imaging was reviewed to document study length, quality and progression of
      oral contrast material. RESULTS: One hundred six children (59 boys [56%]) younger
      than 10 years old underwent 119 MRE examinations (age range: 1 month to 9 years,
      11 months). Common indications for MRE included known IBD (42%) and suspected IBD
      (38%). One hundred ten (92%) examinations were performed under GA. Mean exam
      length was 52 +/- 13 min for GA patients with a range of 31--113 min. Median time
      under GA was 155 min. Oral contrast material reached the terminal ileum in 31%.
      Side effects/adverse events associated with GA were uncommon and minor, including
      transient nausea in 13 children (11%) and emesis in 9 (8%). CONCLUSION:
      Diagnostic-quality MRE can be performed successfully in young children. The
      majority of MRE exams were performed under GA, with only occasional minor side
      effects/adverse events.

PMID- 26224109
TI  - Serum level of taurine would be associated with the amelioration of minimal
      hepatic encephalopathy in cirrhotic patients.
AB  - AIM: A variety of treatment modalities including L-carnitine have been tried for
      cirrhotic patients with minimal hepatic encephalopathy (MHE), which improved MHE
      for some patients, but were not effective for the other patients. We aimed to
      identify pre-therapeutic independent factors to predict the amelioration of MHE
      after L-carnitine treatment. METHODS: We performed a prospective cohort study on
      a total of 64 consecutive outpatients of cirrhotic patients who underwent blood
      biochemical examinations and neuropsychiatric (NP) test at Kobe University
      Hospital. MHE patients diagnosed by the NP test were p.o. administrated L
      carnitine for 3 months. The patients with and without MHE amelioration were
      compared, and the independent factors were statistically examined. Predictive
      scoring systems of the amelioration of MHE were established using multivariate
      logistic regression. RESULTS: The amelioration of MHE was found in 45.8% of MHE
      patients. Serum taurine before the treatment was the best predictive factor of
      the amelioration of MHE (P = 0.046). The predictive model using serum taurine
      discriminated well between patients with and without the amelioration of MHE
      (area under the receiver-operator curve, 0.748; 95% confidence interval, 0.531
      0.901). The predictive scores of the amelioration of MHE enable the patient
      specific probability to be easily looked up. CONCLUSION: Serum taurine before L
      carnitine treatment was shown to be an independent factor associated with the
      amelioration of MHE 3 months after the treatment. The easy pre-therapeutic
      prediction of MHE amelioration after L-carnitine treatment would help in
      improving awareness of the selection of MHE patients with good response to L
      carnitine, thus being beneficial from a financial perspective.

PMID- 26224111
TI  - A novel multi-parameter assay to dissect the pharmacological effects of different
      modes of integrin alphaLbeta2 inhibition in whole blood.
AB  - BACKGROUND AND PURPOSE: The integrin alphaLbeta2 plays central roles in leukocyte
      adhesion and T cell activation, rendering alphaLbeta2 an attractive therapeutic
      target. Compounds with different modes of alphaLbeta2 inhibition are in
      development, currently. Consequently, there is a foreseeable need for bedside
      assays, which allow assessment of the different effects of diverse types of
      alphaLbeta2 inhibitors in the peripheral blood of treated patients. EXPERIMENTAL
      APPROACH: Here, we describe a flow cytometry-based technology that simultaneously
      quantitates alphaLbeta2 conformational change upon inhibitor binding, alphaLbeta2
      expression and T cell activation at the single-cell level in human blood. Two
      classes of allosteric low MW inhibitors, designated alpha I and alpha/beta I
      allosteric alphaLbeta2 inhibitors, were investigated. The first application
      revealed intriguing inhibitor class-specific profiles. KEY RESULTS: Half-maximal
      inhibition of T cell activation was associated with 80% epitope loss induced by
      alpha I allosteric inhibitors and with 40% epitope gain induced by alpha/beta I
      allosteric inhibitors. This differential establishes that inhibitor-induced
      alphaLbeta2 epitope changes do not directly predict the effect on T cell
      activation. Moreover, we show here for the first time that alpha/beta I
      allosteric inhibitors, in contrast to alpha I allosteric inhibitors, provoked
      partial downmodulation of alphaLbeta2, revealing a novel property of this
      inhibitor class. CONCLUSIONS AND IMPLICATIONS: The multi-parameter whole blood
      alphaLbeta2 assay described here may enable therapeutic monitoring of alphaLbeta2
      inhibitors in patients' blood. The assay dissects differential effect profiles of
      different classes of alphaLbeta2 inhibitors.

PMID- 26224113
TI  - Low-Dimensional Conduction Mechanisms in Highly Conductive and Transparent
      Conjugated Polymers.
AB  - Electronic conduction in conjugated polymers is of emerging technological
      interest for high-performance optoelectronic and thermoelectric devices. A
      completely new aspect and understanding of the conduction mechanism on conducting
      polymers is introduced, allowing the applicability of materials to be optimized.
      The charge-transport mechanism is explained by direct experimental evidence with
      a very well supported theoretical model. 

PMID- 26224112
TI  - Unmet information needs and clinical characteristics in patients with
      precancerous oral lesions.
AB  - The purpose of this study was to investigate associated factors of the unmet
      information needs of patients with precancerous oral lesions. For this cross
      sectional descriptive study, we recruited patients with precancerous oral lesions
      from the otolaryngology outpatient department of a single medical centre in
      central Taiwan. Patients were assessed using a set of structure questionnaires to
      measure patients' state anxiety levels, attitudes towards cancer prevention and
      need for information. Patients' anxiety and attitudes towards cancer prevention
      were evaluated based on unmet needs and associated factors were determined. Among
      the 106 subjects surveyed, the most prominent unmet information needs were about
      obtaining the test results as soon as possible. Patients with precancerous oral
      lesions who had high levels of state anxiety, long duration of time since
      quitting betel nut chewing and were without a history of oral cancer were more
      likely to have unmet information needs. A high level of anxiety about
      precancerous oral lesions was more prevalent among patients with unmet
      information needs than among those whose information needs were met. Health
      education and individual counselling should be provided to satisfy the
      information needs of this population. 

PMID- 26224115
TI  - Pre- and post-operative clinical findings of tympanomastoid surgery in female
      divers (Haenyeo) of Jeju Island with chronic otitis media.
AB  - CONCLUSIONS: A tympanomastoid surgery can control chronic otitis media (COM) and
      improve hearing effectively in Jeju women divers (Haenyeo) without any
      complications. OBJECTIVE: To evaluate the long-term results of tympanomastoid
      surgery in Haenyeo patients with COM to determine any link between their diving
      behavior and COM. METHODS: The medical records of 207 COM patients who underwent
      tympanomastoid surgery were reviewed for demographic characteristics, etiologic
      analyses, pre- and post-operative hearing levels, types of tympanomastoid surgery
      with ossiculoplasty, and post-operative complications. The patients were divided
      into a 'Haenyeo COM group' of 98 patients and a 'general COM group' of 109, and
      followed up for at least 3 years. RESULTS: In the audiologic study, the Haenyeo
      COM group showed a relatively larger pre-operative air-bone gap than the general
      COM group. There were no statistically significant differences in middle ear swab
      culture results, the rates of re-perforation of the tympanic membrane or re
      operation, or the risk of post-operative complications between the two groups.
      However, the possibility of COM accompanying cholesteatoma was higher and the
      canal wall down mastoidectomy was more frequently performed in the Haenyeo COM
      group (both p < 0.05).

PMID- 26224114
TI  - Subepicardial delayed gadolinium enhancement in asymptomatic athletes: let
      sleeping dogs lie?
AB  - BACKGROUND: Subepicardial delayed gadolinium enhancement (DGE) patches without
      underlying cardiomyopathy is poorly understood. It is often reported as the
      result of prior silent myocarditis. Its prognostic relevance in asymptomatic
      athletes is unknown; therefore, medical clearance for competitive sports
      participation is debated. This case series aims to relate this pattern of DGE in
      athletes to outcome. METHODS: We report on seven young asymptomatic athletes with
      isolated subepicardial DGE detected during workup of abnormalities on their
      regular screening examination, that is, pathological T-wave inversions on ECG
      (n=4) or ventricular arrhythmias on exercise test (n=3). All underwent a
      comprehensive initial investigation in order to assess left ventricular (LV)
      function at rest and exercise (exercise cardiac MRI and/or exercise
      echocardiography) and occurrence of arrhythmias (exercise test, 24 h-ECG Holter,
      electrophysiological study). All underwent a careful follow-up with biannual
      evaluation. RESULTS: All athletes had extensive subepicardial DGE (12.0+/-4.8% of
      LV mass), predominantly in the lateral wall. Three athletes had non-sustained
      ventricular arrhythmias, whereas two of them had LV ejection fraction <50% at
      rest with no contractile reserve at exercise. During a follow-up of 3.0+/-1.5
      years in the four remaining athletes, two had symptomatic ventricular tachycardia
      and one demonstrated progressive LV dysfunction. Hence, six of seven athletes had
      to be excluded from competitive sports participation. CONCLUSIONS: Isolated large
      areas of subepicardial DGE in an asymptomatic athlete are not benign and require
      a careful evaluation at exercise and a strict follow-up. These findings question
      whether extreme exercise during silent myocarditis may facilitate fibrosis
      generation and adverse remodelling.

PMID- 26224117
TI  - Leishman and Giemsa stain: a new reliable staining technique for blood/bone
      marrow smears.
AB  - INTRODUCTION: Peripheral blood and bone marrow smear examination is an important
      basic tool for the diagnosis of different haematological conditions including
      haematological malignancies. We created a newer modification of the conventional
      Leishman and Giemsa stains as Leishman and Giemsa (L&G) stain and compared the
      efficacy and reliability of this stain with conventional stains. The study was
      performed to evaluate the staining efficacy, feasibility, time and cost of L&G
      stain over the conventional Leishman and Giemsa stains. METHODS: A pilot study
      was carried out in the Department of Haematology of our hospital from October
      2013 to December 2013. Hundred selected cases, each with peripheral blood and
      bone marrow smears were taken, and three sets of the smears were prepared from
      each sample--one for L&G stain and other two--one each for conventional Leishman
      and Giemsa stains. This staining is further incorporated in our routine standard
      operating protocols for staining of all the peripheral blood smears in automated
      stainer, Sysmex SP10. RESULT: The average grading score from each staining
      methods from all the three experts was compiled. The average grading score of L&G
      staining method was noted to be significantly higher than the other two methods
      (analysis of variance test, P value < 0.05). When modified L&G stain (C) was
      compared with stain conventional stains (A and B), a P value of <0.001 was noted
      in all parameters except between Leishman stain and L&G stain in mature RBC and
      WBC nucleus and RBC inclusions (P value between 0.05 and 0.001). CONCLUSION: L&G
      staining is a newer staining technique of immense help in high-throughput
      haematology laboratories by offering a time-saving, cost-effective and better
      staining option to conventional staining methods. It gives a better nuclear and
      cytoplasmic differential staining and can also be used in automated blood
      counters/stainer.

PMID- 26224116
TI  - Simultaneous MEMS-based electro-mechanical phenotyping of breast cancer.
AB  - Carcinomas are the most commonly diagnosed cancers originating in the skin,
      lungs, breasts, pancreas, and other organs and glands. In most of the cases, the
      microenvironment within the tissue changes with the progression of disease. A key
      challenge is to develop a device capable of providing quantitative indicators in
      diagnosing cancer by measuring alteration in electrical and mechanical property
      of the tissues from the onset of malignancy. We demonstrate micro-electro
      mechanical-systems (MEMS) based flexible polymer microsensor array capable of
      simultaneously measuring electro-mechanical properties of the breast tissues
      cores (1 mm in diameter and 10 MUm in thickness) from onset through progression
      of the cancer. The electrical and mechanical signatures obtained from the tissue
      cores shows the capability of the device to clearly demarcate the specific stages
      of cancer in epithelial and stromal regions providing quantitative indicators
      facilitating the diagnosis of breast cancer. The present study shows that electro
      mechanical properties of the breast tissue core at the micro-level are different
      than those at the macro-level. 

PMID- 26224118
TI  - Widespread flower color convergence in Solanaceae via alternate biochemical
      pathways.
AB  - Phenotypic convergence is rampant throughout the tree of life. While recent
      studies have made significant progress in ascertaining the proximate mechanisms
      underlying convergent phenotypes, less is known about the frequency and
      predictability with which convergent phenotypes arise via the same or multiple
      pathways at the macroevolutionary scale. We investigated the proximate causes and
      evolutionary patterns of red flower color in the tomato family, Solanaceae, using
      large-scale data mining and new sequence data to reconstruct a megaphylogeny of
      1341 species. We then combined spectral and anatomical data to assess how many
      times red flowers have evolved, the relative contribution of different pathways
      to independent origins of red, and whether the underlying pathway is predicted by
      phylogenetic relatedness. We estimated at least 30 relatively recent origins of
      red flowers using anthocyanins, carotenoids, or a dual production of both
      pigments, with significant phylogenetic signal in the use of anthocyanins and
      dual production, indicating that closely related red-flowered species tend to
      employ the same mechanism for coloration. Our study is the first to test whether
      developmental pathways exhibit phylogenetic signal and implies that historical
      contingency strongly influences the evolution of new phenotypes. 

PMID- 26224119
TI  - Chaos in high-dimensional dissipative dynamical systems.
AB  - For dissipative dynamical systems described by a system of ordinary differential
      equations, we address the question of how the probability of chaotic dynamics
      increases with the dimensionality of the phase space. We find that for a system
      of d globally coupled ODE's with quadratic and cubic non-linearities with
      randomly chosen coefficients and initial conditions, the probability of a
      trajectory to be chaotic increases universally from ~10(-5)- 10(-4) for d = 3 to
      essentially one for d ~ 50. In the limit of large d, the invariant measure of the
      dynamical systems exhibits universal scaling that depends on the degree of non
      linearity, but not on the choice of coefficients, and the largest Lyapunov
      exponent converges to a universal scaling limit. Using statistical arguments, we
      provide analytical explanations for the observed scaling, universality, and for
      the probability of chaos.

PMID- 26224120
TI  - Galectin-Binding O-Glycosylations as Regulators of Malignancy.
AB  - Cancer cells commonly display aberrant surface glycans and related glycoconjugate
      scaffolds. Compared with their normal counterparts, cancer cell glycans are
      variably produced and often structurally distinct, serving as biomarkers of
      cancer progression or as functional entities to malignancy. The glycan signature
      of a cancer cell is created by the collaborative activities of
      glycosyltransferases, glycosidases, nucleotide-sugar transporters,
      sulfotransferases, and glycan-bearing protein/lipid scaffolds. In a coordinated
      fashion, these factors regulate the synthesis of cancer cell glycans and thus are
      considered correlates of cancer cell behavior. Functionally, cancer cell glycans
      can serve as binding targets for endogenous lectin effectors, such as C-type
      selectins and S-type galectins. There has been a recent surge of important
      observations of the role of glycosytransferases, specifically alpha2,6
      sialyltransferases, in regulating the length and lectin-binding features of
      serine/threonine (O)-glycans found on cancer cells. The capping activity of O
      glycan-specific alpha2,6 sialyltransferases, in particular, has been found to
      regulate cancer growth and metastasis in a galectin-dependent manner. These
      findings highlight the functional importance of cancer cell O-glycans and related
      galectin-binding features in the virulent activity of cancer and raise the
      prospect of targeting cancer cell glycans as effective anticancer therapeutics.

PMID- 26224121
TI  - Mitochondrial DNA in Tumor Initiation, Progression, and Metastasis: Role of
      Horizontal mtDNA Transfer.
AB  - Mitochondrial DNA (mtDNA), encoding 13 out of more than 1,000 proteins of the
      mitochondrial proteome, is of paramount importance for the bioenergetic machinery
      of oxidative phosphorylation that is required for tumor initiation, propagation,
      and metastasis. In stark contrast to the widely held view that mitochondria and
      mtDNA are retained and propagated within somatic cells of higher organisms,
      recent in vitro and in vivo evidence demonstrates that mitochondria move between
      mammalian cells. This is particularly evident in cancer where defective
      mitochondrial respiration can be restored and tumor-forming ability regained by
      mitochondrial acquisition. This paradigm shift in cancer cell biology and
      mitochondrial genetics, concerning mitochondrial movement between cells to meet
      bioenergetic needs, not only adds another layer of plasticity to the armory of
      cancer cells to correct damaged mitochondria, but also points to potentially new
      therapeutic approaches.

PMID- 26224122
TI  - Establishment of biochemistry reference values for healthy Tanzanian infants,
      children and adolescents in Kilimanjaro Region.
AB  - OBJECTIVE: To establish common biochemistry reference intervals for Tanzanian
      infants, children and adolescents living in the Kilimanjaro Region. METHODS: We
      recruited healthy, HIV-uninfected Tanzanian infants, children and youth between
      the ages of 1 month and 17 years from local schools and clinics to participate in
      this study. Only afebrile children without signs of physical or chronic illness
      were enrolled. Nonparametric methods were used to determine 95% reference limits
      and their 90% confidence intervals, with outliers removed by the Tukey method.
      RESULTS: A total of 619 healthy infants, children and adolescents were enrolled
      into the study. Twenty-three biochemistry parameters were measured. Compared to
      US reference intervals, several of the biochemistry parameters showed notable
      differences, namely alkaline phosphatase, phosphorus, amylase and lipase.
      Comparing our data to the US National Institutes of Health (NIH) Division of AIDS
      (DAIDS) grading criteria for classification of adverse events, we found that for
      selected parameters, up to 15% of infants or children in certain age groups would
      have been categorised as having an adverse event as defined by DAIDS.
      CONCLUSIONS: Our study further confirms the need to use locally established
      reference intervals to define reference laboratory parameters among children in
      Africa, rather than relying on those derived from US or European populations. To
      our knowledge, this study provides the first set of locally validated
      biochemistry reference ranges for a paediatric population in Tanzania.

PMID- 26224124
TI  - Anesthesia machine flush valve malfunction: detection, implications and
      resolution.

PMID- 26224123
TI  - Effect of pre-stroke statin use on stroke severity and early functional recovery:
      a retrospective cohort study.
AB  - BACKGROUND: Experimental studies suggest that pre-stroke statin treatment has a
      dual effect of neuroprotection during ischemia and neurorestoration after
      ischemic injury. The aim of this study was to evaluate the effect of pre-stroke
      statin use on initial stroke severity and early clinical outcome. METHODS: We
      used a prospective database enrolling patients with acute ischemic stroke from 12
      hospitals in Korea between April 2008 and January 2012. Primary endpoint was the
      initial stroke severity as measured by the National Institutes of Health Stroke
      Scale (NIHSS) score. Secondary endpoints were good outcome (modified Rankin Scale
      [mRS], 0-2) and overall mRS distribution at discharge. Multivariable regression
      model and propensity score (PS) matching were used for statistical analyses.
      RESULTS: Among the 8340 patients included in this study, 964 patients (11.6%)
      were pre-stroke statin users. The initial NIHSS score (mean [95% CI]) was lower
      among pre-stroke statin users vs. non-users in multivariable analysis (5.7 [5.2
      6.3] versus 6.4 [5.9-6.9], p = 0.002) and PS analysis (5.2 [4.7-5.7] versus 5.7
      [5.4-6.0], p = 0.043). Pre-stroke statin use was associated with increased
      achievement of mRS 0-2 outcome (multivariable analysis: OR [95% CI], 1.55 [1.25
      1.92], p < 0.001; PS matching: OR [95% CI], 1.47 [1.16-1.88]; p = 0.002) and
      favorable shift on the overall mRS distribution (multivariable analysis: OR [95%
      CI], 1.29 [1.12-1.51], p = 0.001; PS matching: OR [95% CI], 1.31 [1.11-1.54]; p =
      0.001). CONCLUSIONS: Pre-stroke statin use was independently associated with
      lesser stroke severity at presentation and better early functional recovery in
      patients with acute ischemic stroke.

PMID- 26224125
TI  - Towards a Fuzzy Bayesian Network Based Approach for Safety Risk Analysis of
      Tunnel-Induced Pipeline Damage.
AB  - Tunneling excavation is bound to produce significant disturbances to surrounding
      environments, and the tunnel-induced damage to adjacent underground buried
      pipelines is of considerable importance for geotechnical practice. A fuzzy
      Bayesian networks (FBNs) based approach for safety risk analysis is developed in
      this article with detailed step-by-step procedures, consisting of risk mechanism
      analysis, the FBN model establishment, fuzzification, FBN-based inference,
      defuzzification, and decision making. In accordance with the failure mechanism
      analysis, a tunnel-induced pipeline damage model is proposed to reveal the cause
      effect relationships between the pipeline damage and its influential variables.
      In terms of the fuzzification process, an expert confidence indicator is proposed
      to reveal the reliability of the data when determining the fuzzy probability of
      occurrence of basic events, with both the judgment ability level and the
      subjectivity reliability level taken into account. By means of the fuzzy Bayesian
      inference, the approach proposed in this article is capable of calculating the
      probability distribution of potential safety risks and identifying the most
      likely potential causes of accidents under both prior knowledge and given
      evidence circumstances. A case concerning the safety analysis of underground
      buried pipelines adjacent to the construction of the Wuhan Yangtze River Tunnel
      is presented. The results demonstrate the feasibility of the proposed FBN
      approach and its application potential. The proposed approach can be used as a
      decision tool to provide support for safety assurance and management in tunnel
      construction, and thus increase the likelihood of a successful project in a
      complex project environment. 

PMID- 26224126
TI  - Cancer survival is a poor indicator of quality of care.

PMID- 26224127
TI  - Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in
      ACS and CAD.
AB  - Platelets play a pivotal role in chronic inflammation leading to progression of
      atherosclerosis and acute coronary events. Recent discoveries on novel mechanisms
      and platelet-dependent inflammatory targets underpin the role of platelets to
      maintain a chronic inflammatory condition in cardiovascular disease. There is
      strong and clinically relevant crosslink between chronic inflammation and
      platelet activation. Antiplatelet therapy is a cornerstone in the prevention and
      treatment of acute cardiovascular events. The benefit of antiplatelet agents has
      mainly been attributed to their direct anti-aggregatory impact. Some anti
      inflammatory off-target effects have also been described. However, it is unclear
      whether these effects are secondary due to inhibition of platelet activation or
      are caused by direct distinct mechanisms interfering with inflammatory pathways.
      This article will highlight novel platelet associated targets that contribute to
      inflammation in cardiovascular disease and elucidate mechanisms by which
      currently available antiplatelet agents evolve anti-inflammatory capacities, in
      particular by carving out the differential mechanisms directly or indirectly
      affecting platelet mediated inflammation. It will further illustrate the
      prognostic impact of antiplatelet therapies by reducing inflammatory marker
      release in recent cardiovascular trials. 

PMID- 26224128
TI  - Simplified technique for injection of Botulinum Toxin to Obturator Internus
      muscle using ultrasound-guided nerve stimulation for persistent pelvic pain.
AB  - Botulinum toxin (BoNT) injections have been used to reduce muscle spasm in the
      presence of severe pelvic pain. However, while pubococcygeus is easily accessed
      vaginally, injection to obturator internus is more complex - with variation in
      operative technique and needle placement confounding the ability to assess
      outcomes. We describe a simplified technique for BoNT injection to obturator
      internus using neurostimulation under ultrasound guidance. 

PMID- 26224129
TI  - Efficacy of Bovine Lactoferrin Supplementation in Preventing Late-onset Sepsis in
      low Birth Weight Neonates: A Randomized Placebo-Controlled Clinical Trial.
AB  - OBJECTIVES: To evaluate the efficacy of bovine lactoferrin (BLF) in preventing
      first episode of late-onset sepsis (LOS) in low birth weight (LBW) neonates.
      METHODS: In this study conducted from May 2012 to July 2013 in the neonatal
      intensive care unit (NICU) of a tertiary care hospital, inborn asymptomatic
      neonates, <2000 g, admitted to NICU in first 12 h of birth with no maternal risk
      factors for sepsis were randomized to receive BLF or placebo from 1st to 28th day
      of life. The incidence of culture-proven sepsis and sepsis-attributable mortality
      after 72 h of life was recorded. Increasing doses of BLF were used with higher
      birth weights. RESULTS: Incidence of first episode of culture-proven LOS was
      significantly lower in the BLF group vs. placebo [2/63 (3.2%) vs. 9/67(13.4%);
      risk ratio, 0.211; 95% CI, 0.044-1.019; p = 0.036]. Statistically significant
      reduction in the sepsis-attributable mortality was also seen after use of
      prophylactic BLF [0/63 (0%) vs. 5/67 (7.5%); p = 0.027]. CONCLUSION: BLF
      supplementation in LBW neonates reduced the incidence of first episode of LOS.

PMID- 26224131
TI  - Clinical translation for endometrial cancer stem cells hypothesis.
AB  - Endometrial cancer is the most frequent gynecological malignancy in developed
      world. Cancer stem cells (CSC) are recognized as a small proportion of cells
      among the tumor cell population that are capable of self-renewal, aberrant
      differentiation, and escape homeostasis. This review aims to systematize the
      existing evidence of CSC of endometrial cancer and its clinical translation. In
      endometrial cancer, the cancer stem cell hypothesis has been studied in vitro
      using the isolation of colony forming units, side population with dye efflux
      capacity, and tumorospheres. The stem cell markers for endometrial cancer do not
      have uniform characteristics, albeit CD133 and aldehyde dehydrogenase (ALDH) were
      being associated with CSC phenotype. The application of endometrial CSC on
      xenograft models proves the tumorigenic capacity of this small group of cells.
      The metastatic process has been explained due to epithelial-mesenchymal
      transition (EMT) in which CSC seems to have a critical role. The chemoresistance
      is characteristic of CSC that in endometrial cancer has been shown in CSC
      phenotype and associated with CSC markers. The most ambitious potential for CSC
      is the development of targeted therapies. Its application on endometrial cancer
      is still poor, being a future perspective for research. 

PMID- 26224132
TI  - Revisit dietary fiber on colorectal cancer: butyrate and its role on prevention
      and treatment.
AB  - Colorectal cancer is still a major health problem worldwide. Based on the most
      recent released data by the World Health Organization GLOBOCAN in 2012,
      colorectal cancer is the third most prevalent type of cancer in males and the
      second in females. In 1999, it was published the first report showing evidence of
      a strong correlation between diet and cancer incidence, being its positive or
      negative impact intimately linked to dietary patterns. A diet rich in fiber is
      associated with a low risk of developing colorectal cancer. The fermentation of
      the dietary fiber by intestinal microflora results in production of butyrate,
      which plays a plurifunctional role on the colonocytes, and it has also been
      reported as a chemopreventive agent. However, there are limited studies focusing
      its anti-cancer potential. Here, we review the recent new insights that focus
      butyrate and its role in colorectal cancer prevention and treatment, from its
      synthesis, metabolism, and transport, through its involvement on several cancer
      related signaling pathways, to the novel existing approaches for its clinical
      use. 

PMID- 26224134
TI  - Clinical outcomes of hydronephrosis in patients with systemic lupus
      erythematosus.
AB  - AIM: Hydronephrosis is a rare complication of systemic lupus erythematosus (SLE).
      Bladder and/or gastrointestinal involvement in SLE are associated with
      development of hydronephrosis, but the management and treatment outcomes of
      hydronephrosis are largely unknown. Therefore, we investigated the clinical
      manifestations and factors associated with the treatment response in patients
      with SLE complicated by hydronephrosis. METHOD: A retrospective analysis was
      performed of all 634 SLE patients who underwent computed tomography and/or
      ultrasonography between January 1998 and December 2013. We reviewed the clinical
      characteristics and treatment outcomes of patients with SLE-associated
      hydronephrosis. RESULTS: Hydronephrosis was identified in 15 patients with SLE
      complicated by cystitis and/or enteritis. All patients were treated initially
      with moderate to high doses of corticosteroids. A follow-up imaging study showed
      that 11 (73.3%) of 15 patients experienced improvements in hydronephrosis, and
      urinary obstruction was resolved without urological intervention in the majority
      of these patients (8/11, 72.7%). The four patients who experienced no improvement
      in hydronephrosis were older than those who responded to treatment (median age
      [interquartile range]; 43.0 [37.5-53.0] years vs. 28.0 [21.0-38.5] years; P =
      0.026). In addition, delayed treatment (>= 1 month after onset of symptoms) with
      corticosteroids was more frequently observed in the non-responding patients than
      in the responding patients (P = 0.011). CONCLUSION: Our findings suggest that
      treatment with corticosteroids alone leads to favorable outcomes in patients with
      SLE-associated hydronephrosis, except when treatment is delayed, particularly in
      elderly patients.

PMID- 26224133
TI  - Fibroblast growth factor receptor signaling in hereditary and neoplastic disease:
      biologic and clinical implications.
AB  - Fibroblast growth factors (FGFs) and their receptors (FGFRs) are transmembrane
      growth factor receptors with wide tissue distribution. FGF/FGFR signaling is
      involved in neoplastic behavior and also development, differentiation, growth,
      and survival. FGFR germline mutations (activating) can cause skeletal disorders,
      primarily dwarfism (generally mutations in FGFR3), and craniofacial malformation
      syndromes (usually mutations in FGFR1 and FGFR2); intriguingly, some of these
      activating FGFR mutations are also seen in human cancers. FGF/FGFR aberrations
      reported in cancers are mainly thought to be gain-of-function changes, and
      several cancers have high frequencies of FGFR alterations, including breast,
      bladder, or squamous cell carcinomas (lung and head and neck). FGF ligand
      aberrations (predominantly gene amplifications) are also frequently seen in
      cancers, in contrast to hereditary syndromes. There are several pharmacologic
      agents that have been or are being developed for inhibition of FGFR/FGF
      signaling. These include both highly selective inhibitors as well as multi-kinase
      inhibitors. Of note, only four agents (ponatinib, pazopanib, regorafenib, and
      recently lenvatinib) are FDA-approved for use in cancer, although the approval
      was not based on their activity against FGFR. Perturbations in the FGFR/FGF
      signaling are present in both inherited and malignant diseases. The development
      of potent inhibitors targeting FGF/FGFR may provide new tools against disorders
      caused by FGF/FGFR alterations. 

PMID- 26224135
TI  - Selective Generation of Dopaminergic Precursors from Mouse Fibroblasts by Direct
      Lineage Conversion.
AB  - Degeneration of midbrain dopaminergic (DA) neurons is a key pathological event of
      Parkinson's disease (PD). Limited adult dopaminergic neurogenesis has led to
      novel therapeutic strategies such as transplantation of dopaminergic precursors
      (DPs). However, this strategy is currently restrained by a lack of cell source,
      the tendency for the DPs to become a glial-restricted state, and the tumor
      formation after transplantation. Here, we demonstrate the direct conversion of
      mouse fibroblasts into induced DPs (iDPs) by ectopic expression of Brn2, Sox2 and
      Foxa2. Besides expression with neural progenitor markers and midbrain genes
      including Corin, Otx2 and Lmx1a, the iDPs were restricted to dopaminergic
      neuronal lineage upon differentiation. After transplantation into MPTP-lesioned
      mice, iDPs differentiated into DA neurons, functionally alleviated the motor
      deficits, and reduced the loss of striatal DA neuronal axonal termini.
      Importantly, no iDPs-derived astrocytes and neoplasia were detected in mouse
      brains after transplantation. We propose that the iDPs from direct reprogramming
      provides a safe and efficient cell source for PD treatment.

PMID- 26224137
TI  - Patients' experience with cancer recurrence: a meta-ethnography.
AB  - OBJECTIVE: Recurrence is a difficult stage in the cancer journey as it brings to
      the fore the life-threatening nature of the illness. This meta-ethnography
      examines and synthesises the findings of qualitative research regarding patients'
      experience of cancer recurrence. METHODS: A systematic search of the qualitative
      studies published between January 1994 to April 2014 was undertaken. Seventeen
      relevant papers were identified, and a meta-ethnography was conducted. RESULTS:
      Six third-order concepts were developed to capture patients' experiences:
      experiencing emotional turmoil following diagnosis, which described the emotional
      impact of diagnosis and the influence of previous experiences on how the news
      were received; experiencing otherness, encompassing changed relationships;
      seeking support in the health care system, describing the extent of information
      needs and the importance of the relationship with health care professionals;
      adjusting to a new prognosis and uncertain future, highlighting the changes
      associated with uncertainty; finding strategies to deal with recurrence,
      describing ways of maintaining emotional well-being and regaining a sense of
      control over cancer; and facing mortality, describing the difficulties in facing
      death-related concerns and associated consequences. CONCLUSIONS: This meta
      ethnography clarifies the fundamental aspects of patients' experience of
      recurrence. It suggests that health care professionals can promote a positive
      experience of care and help lessen the psychosocial impact of recurrence by
      providing information in an approachable way and being sensitive to their
      changing needs. It also points to the importance of supporting patients in
      adopting strategies to regain a sense of control and to address their potential
      mortality and its impact on loved ones.

PMID- 26224136
TI  - Parental age effects on odor sensitivity in healthy subjects and schizophrenia
      patients.
AB  - A schizophrenia phenotype for paternal and maternal age effects on illness risk
      could benefit etiological research. As odor sensitivity is associated with
      variability in symptoms and cognition in schizophrenia, we examined if it was
      related to parental ages in patients and healthy controls. We tested Leukocyte
      Telomere Length (LTL) as an explanatory factor, as LTL is associated with
      paternal age and schizophrenia risk. Seventy-five DSM-IV patients and 46 controls
      were assessed for detection of PEA, WAIS-III for cognition, and LTL, assessed by
      qPCR. In healthy controls, but not schizophrenia patients, decreasing sensitivity
      was monotonically related to advancing parental ages, particularly in sons. The
      relationships between parental aging and odor sensitivity differed significantly
      for patients and controls (Fisher's R to Z: chi(2)  = 6.95, P = 0.009). The
      groups also differed in the association of odor sensitivity with cognition;
      lesser sensitivity robustly predicted cognitive impairments in patients (<0.001),
      but these were unassociated in controls. LTL was unrelated to odor sensitivity
      and did not explain the association of lesser sensitivity with cognitive
      deficits.Parental aging predicted less sensitive detection in healthy subjects
      but not in schizophrenia patients. In patients, decreased odor sensitivity
      strongly predicted cognitive deficits, whereas more sensitive acuity was
      associated with older parents. These data support separate risk pathways for
      schizophrenia. A parental age-related pathway may produce psychosis without
      impairing cognition and odor sensitivity. Diminished odor sensitivity may
      furthermore be useful as a biomarker for research and treatment studies in
      schizophrenia. (c) 2015 Wiley Periodicals, Inc.

PMID- 26224138
TI  - The Risk Instrument for Screening in the Community (RISC): a new instrument for
      predicting risk of adverse outcomes in community dwelling older adults.
AB  - BACKGROUND: Predicting risk of adverse healthcare outcomes, among community
      dwelling older adults, is difficult. The Risk Instrument for Screening in the
      Community (RISC) is a short (2-5 min), global subjective assessment of risk
      created to identify patients' 1-year risk of three outcomes:institutionalisation,
      hospitalisation and death. METHODS: We compared the accuracy and predictive
      ability of the RISC, scored by Public Health Nurses (PHN), to the Clinical
      Frailty Scale (CFS) in a prospective cohort study of community dwelling older
      adults (n = 803), in two Irish PHN sectors. The area under the curve (AUC), from
      receiver operating characteristic curves and binary logistic regression models,
      with odds ratios (OR), compared the discriminatory characteristics of the RISC
      and CFS. RESULTS: Follow-up data were available for 801 patients. The 1-year
      incidence of institutionalisation, hospitalisation and death were 10.2, 17.7 and
      15.6 % respectively. Patients scored maximum-risk (RISC score 3,4 or 5/5) at
      baseline had a significantly greater rate of institutionalisation (31.3 and 7.1
      %, p < 0.001), hospitalisation (25.4 and 13.2 %, p < 0.001) and death (33.5 and
      10.8 %, p < 0.001), than those scored minimum-risk (score 1 or 2/5). The RISC had
      comparable accuracy for 1-year risk of institutionalisation (AUC of 0.70 versus
      0.63), hospitalisation (AUC 0.61 versus 0.55), and death (AUC 0.70 versus 0.67),
      to the CFS. The RISC significantly added to the predictive accuracy of the
      regression model for institutionalisation (OR 1.43, p = 0.01), hospitalisation
      (OR 1.28, p = 0.01), and death (OR 1.58, p = 0.001). CONCLUSION: Follow-up
      outcomes matched well with baseline risk. The RISC, a short global subjective
      assessment, demonstrated satisfactory validity compared with the CFS.

PMID- 26224140
TI  - Sheath rendezvous method: a novel distal protection technique during endovascular
      treatment of subclavian artery occlusions.
AB  - To describe an innovative distal protection technique, "sheath rendezvous
      method", during endovascular treatment for subclavian arterial occlusions. 4.5F
      and 6F guiding sheath were inserted from left brachial and common femoral artery,
      respectively. 0.014" guidewire retrogradely passed through occlusion and into
      antegrade sheath to establish a pull-through system. 3.0 mm balloon was used to
      expand occlusion and anchor to deliver retrograde sheath into antegrade one. Both
      sheaths locked by balloon dilatation crossed occlusion until antegrade sheath
      passed over lesion. Balloon expandable stent was delivered within antegrade
      sheath. Sheath was removed, and stent was implanted. We obtained an excellent
      outcome without complications. 

PMID- 26224139
TI  - Quality indicators in continuous renal replacement therapy (CRRT) care in
      critically ill patients: protocol for a systematic review.
AB  - BACKGROUND: Renal replacement therapy is increasingly utilized in the intensive
      care unit (ICU), of which continuous renal replacement therapy (CRRT) is most
      common. Despite CRRT being a relatively resource-intensive and expensive
      technology, there remains wide practice variation in its application. This
      systematic review will appraise the evidence for quality indicators (QIs) of CRRT
      care in critically ill patients. METHODS: Ovid MEDLINE, Ovid EMBASE, CINAHL, and
      the Cochrane Library including the Cochrane Database of Systematic Reviews, the
      Cochrane Central Register of Controlled Trials (CENTRAL), and databases from the
      National Information Center of Health Services Research and Health Care
      Technology will be searched for original studies involving QIs in CRRT. Gray
      literature sources will be searched for technical reports, practice guidelines,
      and conference proceedings. Websites of relevant organizations will be
      identified, and industry leaders in the development and marketing of CRRT
      technology and non-profit organizations that represent key opinion leads in the
      use of CRRT will be contacted. We will search the Agency of Healthcare Research
      and Quality National Quality Measures Clearinghouse for CRRT-related QIs. Studies
      will be included if they contain quality measures, occur in critically ill
      patients, and are associated with CRRT. Analysis will be primarily descriptive.
      Each QI will be evaluated for importance, scientific acceptability, usability,
      and feasibility using the four criteria proposed by the United States Strategic
      Framework Board for a National Quality Measurement and Reporting System. Finally,
      QIs will be appraised for their potential operational characteristics, for their
      potential to be integrated into electronic medical records, and on their
      affordability, if applicable. DISCUSSION: This systematic review will
      comprehensively identify and synthesize QIs in CRRT. The results of this study
      will fuel the development of an inventory of essential QIs to support the
      appropriate, safe, and efficient delivery of CRRT in critically ill patients.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015530.

PMID- 26224142
TI  - Effect of magnetic resonance imaging on microleakage of amalgam restorations: an
      in vitro study.

PMID- 26224141
TI  - Antiviral Phosphorodiamidate Morpholino Oligomers are Protective against
      Chikungunya Virus Infection on Cell-based and Murine Models.
AB  - Chikungunya virus (CHIKV) infection in human is associated with debilitating and
      persistent arthralgia and arthritis. Currently, there is no specific vaccine or
      effective antiviral available. Anti-CHIKV Phosphorodiamidate Morpholino Oligomer
      (CPMO) was evaluated for its antiviral efficacy and cytotoxcity in human cells
      and neonate murine model. Two CPMOs were designed to block translation initiation
      of a highly conserved sequence in CHIKV non-structural and structural
      polyprotein, respectively. Pre-treatment of HeLa cells with CPMO1 significantly
      suppressed CHIKV titre, CHIKV E2 protein expression and prevented CHIKV-induced
      CPE. CPMO1 activity was also CHIKV-specific as shown by the lack of cross
      reactivity against SINV or DENV replication. When administered prophylactically
      in neonate mice, 15 MUg/g CPMO1v conferred 100% survival against CHIKV disease.
      In parallel, these mice demonstrated significant reduction in viremia and viral
      load in various tissues. Immunohistological examination of skeletal muscles and
      liver of CPMO1v-treated mice also showed healthy tissue morphology, in contrast
      to evident manifestation of CHIKV pathogenesis in PBS- or scrambled sCPMO1v
      treated groups. Taken together, our findings highlight for the first time that
      CPMO1v has strong protective effect against CHIKV infection. This warrants future
      development of morpholino as an alternative antiviral agent to address CHIKV
      infection in clinical applications.

PMID- 26224143
TI  - Can A Denaturant Stabilize DNA? Pyridine Reverses DNA Denaturation in Acidic pH.
AB  - The stability of DNA is highly dependent on the properties of the surrounding
      solvent, such as ionic strength, pH, and the presence of denaturants and
      osmolytes. Addition of pyridine is known to unfold DNA by replacing pi-pi
      stacking interactions between bases, stabilizing conformations in which the
      nucleotides are solvent exposed. We show here experimental and theoretical
      evidences that pyridine can change its role and in fact stabilize the DNA under
      acidic conditions. NMR spectroscopy and MD simulations demonstrate that the
      reversal in the denaturing role of pyridine is specific, and is related to its
      character as pseudo groove binder. The present study sheds light on the nature of
      DNA stability and on the relationship between DNA and solvent, with clear
      biotechnological implications. 

PMID- 26224144
TI  - Invasive bark beetle-associated microbes degrade a host defensive monoterpene.
AB  - Conifers respond to herbivore attack with defensive chemicals, which are toxic to
      both insects and their associated microorganisms. Microorganisms associated with
      insects have been widely reported to metabolize toxic chemicals, which may help
      both microorganisms and host insects overcome host conifer defense. Dendroctonus
      valens LeConte, an introduced exotic pest from North America to China, has killed
      millions of healthy pines. Alpha-pinene is the most abundant defensive
      monoterpene in Chinese Pinus tabuliformis. Although microorganisms associated
      with D. valens have already been investigated, little is known about their
      bioactivities when encountering host defensive monoterpenes. In this study, we
      evaluated the influences of different concentrations of alpha-pinene to D. valens
      and the three most frequently isolated yeasts and bacteria of D. valens, and
      further assayed microorganisms' capabilities to degrade alpha-pinene. Results
      showed that the gallery lengths and body weight changes of bark beetles were
      significantly affected by 6 mg/mL and 12 mg/mL of alpha-pinene applied in media
      compared to controls. The tolerance of experimental microorganisms to alpha
      pinene varied depending on the microbial species. Two out of three yeast strains
      and all three bacterial strains degraded 20%-50% of alpha-pinene compared to
      controls in 24 h in vitro. The microorganisms capable of alpha-pinene degradation
      in vitro and their tolerance to high levels of alpha-pinene suggested that D.
      valens-associated microorganisms may help both microorganisms and the bark beetle
      overcome host alpha-pinene defense. 

PMID- 26224145
TI  - Ergonomics standards and guidelines for computer workstation design and the
      impact on users' health - a review.
AB  - This paper presents an overview of global ergonomics standards and guidelines for
      design of computer workstations, with particular focus on their inconsistency and
      associated health risk impact. Overall, considerable disagreements were found in
      the design specifications of computer workstations globally, particularly in
      relation to the results from previous ergonomics research and the outcomes from
      current ergonomics standards and guidelines. To cope with the rapid advancement
      in computer technology, this article provides justifications and suggestions for
      modifications in the current ergonomics standards and guidelines for the design
      of computer workstations. Practitioner Summary: A research gap exists in
      ergonomics standards and guidelines for computer workstations. We explore the
      validity and generalisability of ergonomics recommendations by comparing previous
      ergonomics research through to recommendations and outcomes from current
      ergonomics standards and guidelines. 

PMID- 26224146
TI  - Methylome sequencing for fibrolamellar hepatocellular carcinoma depicts
      distinctive features.
AB  - With the goal of studying epigenetic alterations in fibrolamellar hepatocellular
      carcinoma (FLC) and establish an associated DNA methylation signature, we
      analyzed LINE-1 methylation in a cohort of FLC and performed next-generation
      sequencing of DNA methylation in a training set of pure-FLCs and non-cirrhotic
      hepatocellular carcinomas (nc-HCC). DNA methylation was correlated with gene
      expression. Furthermore, we established and validated an epigenetic signature
      differentiating pure-FLC from other HCCs. LINE-1 methylation correlated with
      shorter recurrence-free survival and overall survival in resected pure-FLC
      patients. Unsupervised clustering using CG sites located in islands distinguished
      pure-FLC from nc-HCC. Major DNA methylation changes occurred outside promoters,
      mainly in gene bodies and intergenic regions located in the vicinity of liver
      developmental genes (i.e., SMARCA4 and RXRA). Partially methylated domains were
      more prone to DNA methylation changes. Furthermore, we identified several
      putative tumor suppressor genes (e.g., DLEU7) and oncogenes (e.g., DUSP4). While
      ~ 70% of identified gene promoters gaining methylation were marked by bivalent
      histone marks (H3K4me3/H3K27me3) in embryonic stem cells, ~ 70% of those losing
      methylation were marked by H3K4me3. Finally, we established a pure FLC DNA
      methylation signature and validated it in an independent dataset. Our analysis
      reveals a distinct epigenetic signature of pure FLC as compared to nc-HCC, with
      DNA methylation changes occurring in the vicinity of liver developmental genes.
      These data suggest new options for targeting FLC based on cancer epigenome
      aberrations.

PMID- 26224147
TI  - Three-Dimensional Integrated Survey for Building Investigations.
AB  - The study shows the results of a survey aimed to represent a building collapse
      and the feasibility of the modellation as a support of structure analysis. An
      integrated survey using topographic, photogrammetric, and terrestrial laser
      techniques was carried out to obtain a three-dimensional (3D) model of the
      building, plans and prospects, and the particulars of the collapsed area. Authors
      acquired, by a photogrammetric survey, information about regular parties of the
      structure; while using laser scanner data they reconstructed a set of more
      interesting architectural details and areas with higher surface curvature.
      Specifically, the process of texture provided a detailed 3D structure of the
      areas under investigation. The analysis of the data acquired resulted to be very
      useful both in identifying the causes of the disaster and also in helping the
      reconstruction of the collapsed corner showing the contribution that the
      integrated surveys can give in preserving architectural and historic heritage.

PMID- 26224148
TI  - Quantification of fluid shear stress in bone tissue engineering scaffolds with
      spherical and cubical pore architectures.
AB  - Recent studies have shown that mechanical stimulation, in the form of fluid
      perfusion and mechanical compression, can enhance osteogenic differentiation of
      mesenchymal stem cells and bone cells within tissue engineering scaffolds in
      vitro. The precise nature of mechanical stimulation within tissue engineering
      scaffolds is not only dictated by the exogenously applied loading regime, but
      also depends on the geometric features of the scaffold, in particular
      architecture, pore size and porosity. However, the precise contribution of each
      geometric feature towards the resulting mechanical stimulation within a scaffold
      is difficult to characterise due to the wide range of interacting parameters. In
      this study, we have applied a fluid-structure interaction model to investigate
      the role of scaffold geometry (architecture, pore size and porosity) on pore wall
      shear stress (WSS) under a range of different loading scenarios: fluid perfusion,
      mechanical compression and a combination of perfusion and compression. It is
      found that scaffold geometry (spherical and cubical pores), in particular the
      pore size, has a significant influence on the stimulation within scaffolds.
      Furthermore, we observed an amplified WSS within scaffolds under a combination of
      fluid perfusion and mechanical compression, which exceeded that caused by
      individual fluid perfusion or mechanical compression approximately threefold. By
      conducting this comprehensive parametric variation study, an expression was
      generated to allow the design and optimisation of 3D TE scaffolds and inform
      experimental loading regimes so that a desired level of mechanical stimulation,
      in terms of WSS is generated within the scaffold.

PMID- 26224149
TI  - Three-Ring-Based Room-Temperature Bent-Core Nematic Compounds: Synthesis and
      Characterization.
AB  - We report the synthesis and characterization of a new class of achiral three-ring
      bent-core compounds with an amide and ester linkage at the molecular bend, which
      are shown to exhibit nematic/phases in wide temperature ranges around room
      temperature (RT) and undulated SmC phases below RT. In contrast to previous
      studies, the compounds reported in this Communication show a true RT nematic
      phase with fluid physical appearance. They show strong photoluminescence in the
      mesophase and are found to display a one-dimensional array of intermolecular
      hydrogen bonding. Furthermore, the nematic phases exhibited by these compounds
      show a good homeotropic alignment that can be exploited in applications such as
      optics and sensing. Considering the scarcity of bent-core materials exhibiting an
      RT nematic mesophase, this new class of materials is promising.

PMID- 26224150
TI  - Clinic First: Prioritizing Primary Care Outpatient Training for Family Medicine
      Residents at Group Health Cooperative.

PMID- 26224151
TI  - Capsule Commentary on Kiechle et. al, Different Measures, Different Outcomes? A
      Systematic Review of Performance-Based versus Self-Reported Measures of Health
      Literacy and Numeracy.

PMID- 26224152
TI  - Capsule Commentary on Al-Khatib et al., Future Research Prioritization:
      Implantable Cardioverter Defibrillator Therapy in Older Patients.

PMID- 26224153
TI  - Use of Interpreters by Physicians.

PMID- 26224154
TI  - Patient-Reported Outcomes as a Measure of Healthcare Quality.

PMID- 26224155
TI  - Medical Debates and Medical Reversal.

PMID- 26224157
TI  - Management Strategies for Post-Prostatectomy Bladder Neck Contractures.
AB  - Patients who develop bladder neck contracture (BNC) after surgical treatment for
      prostate cancer often present with progressive lower urinary tract symptoms.
      Multiple risk factors contribute to BNC development including patient-related
      factors and technical considerations at the time of surgery. Initial management
      begins with endoscopic therapies, including dilation, transurethral incision
      (TUIBNC), and injection of adjunctive agents. When BNC remains refractory to
      these therapies, surgical reconstruction of the vesicourethral anastomosis or
      urinary diversion can be considered in select cases. This review presents an
      outline of the management of BNC after radical prostatectomy (RP), highlighting
      the recent literature related to the subject. 

PMID- 26224158
TI  - C-F bond substitution via aziridinium ion intermediates.
AB  - Aliphatic 1,2-aminofluorides undergo extremely fast substitution reactions under
      the influence of lanthanum tris(hexamethyldisilazide). The substitution proceeds
      via an in situ generated aziridinium ion intermediate, which subsequently
      undergoes ring opening by addition of a nucleophile, yielding various beta
      substituted amines. 

PMID- 26224156
TI  - TAR DNA-binding protein 43 and pathological subtype of Alzheimer's disease impact
      clinical features.
AB  - OBJECTIVE: The aim of this study was to determine whether the frequency of TAR
      DNA-binding protein 43 (TDP-43) deposition in Alzheimer's disease (AD) differs
      across pathologically defined AD subtypes (hippocampal sparing [HpSp]; typical
      and limbic) and further examine the relationship between TDP-43, pathological
      subtype, and clinical features in AD. METHODS: We identified all cases with
      pathologically confirmed AD (NIA-Reagan intermediate-high probability, Braak
      stage IV-VI) independent of cognitive status (n = 188). Neurofibrillary tangle
      counts were performed using thioflavin-S microscopy in hippocampus and three
      neocortical regions, and all cases were subtyped: HpSp AD pathology (n = 19);
      typical AD pathology (n = 136); and limbic AD pathology (n = 33). TDP-43
      immunoreactivity was performed in multiple brain regions to assess for the
      presence of TDP-43 and TDP-43 stage. All cases were clinically subclassified at
      presentation as amnestic AD dementia versus atypical AD dementia. Statistical
      analysis was performed using linear and penalized logistic regression to assess
      associations with pathological subtype, and the effects of TDP-43, accounting for
      possible interactions between pathological subtype and TDP-43. RESULTS: TDP-43
      deposition was frequent in typical (59%) and limbic AD pathologies (67%), but not
      HpSp AD pathology (21%; p = 0.003). The observed associations of TDP-43 with
      greater memory loss, naming and functional decline, and smaller hippocampal
      volumes, closest to death, did not differ across AD pathological subtype.
      Clinical presentation was associated with pathological subtype (p = 0.01), but
      not TDP-43 (p = 0.69). INTERPRETATION: Although the frequency of TDP-43
      deposition in AD varies by pathological subtype, the observed effects of TDP-43
      on clinical/magnetic resonance imaging features are consistent across
      pathological subtypes. Clinical presentation in AD is driven by pathological
      subtype, not by TDP-43.

PMID- 26224159
TI  - 3,4,5-Tricaffeoylquinic Acid Attenuates TRAIL-induced Apoptosis in Human
      Keratinocytes by Suppressing Apoptosis-related Protein Activation.
AB  - Caffeoyl derivatives exhibit antiinflammatory and antioxidant effects. However,
      the effect of 3,4,5-tricaffeoylquinic acid on the tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL)-induced apoptosis in keratinocytes that may be
      involved in skin diseases has not been studied. In this respect, we investigated
      the effect of 3,4,5-tricaffeoylquinic acid on TRAIL-induced apoptosis in human
      keratinocytes. 3,4,5-Tricaffeoylquinic acid and oxidant scavengers attenuated the
      decrease in the cytosolic levels of Bid, Bcl-2, and survivin proteins; the
      increase in the levels of cytosolic Bax, p53, and phosphorylated p53; the
      increase in the levels of phosphorylated p38; the increase in the mitochondrial
      levels of the voltage-dependent anion channel; loss of the mitochondrial
      transmembrane potential; the release of cytochrome c; activation of caspases (8,
      9, and 3); cleavage of poly [ADP-ribose] polymerase-1; production of reactive
      oxygen species; the depletion of glutathione (GSH); nuclear damage; and cell
      death in keratinocytes treated with TRAIL. These results suggest that 3,4,5
      tricaffeoylquinic acid may reduce TRAIL-induced apoptosis in human keratinocytes
      by suppressing the activation of the caspase-8 and Bid pathways and the
      mitochondria-mediated cell death pathway. The effect appears to be associated
      with the inhibitory effect on the production of reactive oxygen species and
      depletion of GSH. 3,4,5-Tricaffeoylquinic acid appears to be effective in the
      prevention of TRAIL-induced apoptosis-mediated skin diseases.

PMID- 26224160
TI  - Involvement of CD9 and PDGFR in migration is evolutionarily conserved from
      Drosophila glia to human glioma.
AB  - Platelet-derived growth factor receptor (PDGFR) signaling plays an important role
      in the biology of malignant gliomas. To investigate mechanisms modulating PDGFR
      signaling in gliomagenesis, we employed a Drosophila glioma model and genetic
      screen to identify genes interacting with Pvr, the fly homolog of PDGFRs. Glial
      expression of constitutively activated Pvr (lambdaPvr) led to glial over
      migration and lethality at late larval stage. Among 3316 dsRNA strains crossed
      against the tester strain, 128 genes shifted lethality to pupal stage, including
      tetraspanin 2A (tsp2A). In a second step knockdown of all Drosophila tetraspanins
      was investigated. Of all tetraspanin dsRNA strains only knockdown of tsp2A
      partially rescued the Pvr-induced phenotype. Human CD9 (TSPAN29/MRP-1), a close
      homolog of tsp2A, was found to be expressed in glioma cell lines A172 and U343MG
      as well as in the majority of glioblastoma samples (16/22, 73 %). Furthermore, in
      situ proximity ligation assay revealed close association of CD9 with PDGFR alpha
      and beta. In U343MG cells, knockdown of CD9 blocked PDGF-BB stimulated migration.
      In conclusion, modulation of PDGFR signaling by CD9 is evolutionarily conserved
      from Drosophila glia to human glioma and plays a role in glia migration. 

PMID- 26224162
TI  - The self-evaluation of upper-gastrointestinal symptoms in Chinese patients with
      digestive disease: A multicenter questionnaire survey.
AB  - AIM: To investigate the self-evaluation of upper gastrointestinal symptoms in
      Chinese patients. To observe the role of patients' characters, such as sex, age,
      education background, and clinic visits, which might affect the self
      understanding of patients. METHODS: The nationwide cross-sectional questionnaire
      was administered to 3000 patients with upper gastrointestinal symptoms at 50
      hospitals across 9 provinces in China. Questionnaire items covered four basic
      patients' characters and five major upper gastrointestinal symptoms. RESULTS: A
      total of 2799 questionnaires (response rate: 93.3%) were analyzed. Only 35.29%
      patients could precisely understand the definition of dyspepsia. The
      misunderstanding of lower-gastroenterology discomforts is the major reason
      leading to low accuracy rate of dyspepsia. The accuracy rate of early satiety and
      postprandial fullness is 37.7% and 52.27% separately; they are most interrelated
      and easily confused concepts to each other. The accuracy rate of heartburn is
      30.02%, while the location of burning sensation is the key aspect for
      misunderstanding of heartburn. The self-understanding of symptoms in patients was
      decreased with increasing age, and enhanced with higher education background and
      time of clinic visits. Gender is not the independent factor. CONCLUSION: Based on
      the low accuracy rate of self-understanding of patients, this survey suggests
      that the gastroenterologists should re-evaluate the symptoms of patients during
      the clinical inquiry.

PMID- 26224163
TI  - Patchiness in a microhabitat chip affects evolutionary dynamics of bacterial
      cooperation.
AB  - Localized interactions are predicted to favour the evolution of cooperation
      amongst individuals within a population. One important factor that can localize
      interactions is habitat patchiness. We hypothesize that habitats with greater
      patchiness (greater edge-to-area ratio) can facilitate the maintenance of
      cooperation. This outcome is believed to be particularly relevant in pathogenic
      microbes that can inhabit patchy habitats such as the human respiratory tract. To
      test this hypothesis in a simple but spatially controlled setting, we designed a
      transparent microhabitat chip (MHC) with multiple patchiness treatments at the
      100 micron scale. The MHC is a closed system that sustains bacterial replication
      and survival for up to 18 hours, and allows spatial patterns and eco-evolutionary
      dynamics to be observed undisturbed. Using the opportunistic pathogen Pseudomonas
      aeruginosa, we tracked the growth of wild-type cooperators, which produce the
      public good pyoverdin, in competition with mutant defectors or cheaters that use,
      but do not produce, pyoverdin. We found that while defectors on average
      outperformed cooperators in all habitats, habitat patchiness significantly
      alleviated the ecological pressure against cooperation due to defection, leading
      to coexistence. Our results confirmed that habitat-level spatial heterogeneity
      can be important for cooperation. The MHC enables novel experiments, allows
      multiple parameters to be precisely varied and studied simultaneously, and will
      help uncover dynamical features of spatial ecology and the evolution of
      pathogens. 

PMID- 26224161
TI  - Differential gene methylation in paired glioblastomas suggests a role of immune
      response pathways in tumor progression.
AB  - DNA and histone methylation are post-transcriptional modifications that have been
      recently described in gliomas. Indeed, glioma CpG island hypermethylated
      phenotype has been identified as prognostic biomarker and as a surrogate marker
      of IDH1/2 mutations. However, the role of DNA methylation in glioblastoma
      progression is unknown. We sought to analyze DNA methylation levels in paired
      (initial and recurrent) primary glioblastoma samples to identify candidate
      pathways that may prone to glioblastoma progression. We have analyzed 12 samples
      (5 paired samples, two of them with three surgeries) using methylation arrays. We
      have analyzed differential methylation at probe and at gene region level.
      Finally, pathway analysis has been performed using differentially methylated
      regions. All analysis has been performed with R and Bioconductor packages. Mean
      methylation level at initial sample compared to recurrence was strongly
      positively correlated (R(2) = 0.98). There was no differentially methylation at
      probe level. However, at gene level 3080 regions were differentially methylated.
      Interestingly, pathways analysis showed that the most differentially methylated
      genes are involved in cellular response to macrophage colony-stimulating factor
      stimulus (GO:0036006). Methylation levels were strongly conserved when comparing
      initial to recurrence in primary glioblastomas. Interestingly, differentially
      methylated pathway analysis suggests that a modulation of methylation in immune
      response genes may play a role in glioblastoma progression. Further studies are
      needed to validate the role of methylation of glioblastoma immune response genes
      in tumor progression. 

PMID- 26224166
TI  - Haploinsufficiency caused by a nonsense mutation in NCSTN underlying hidradenitis
      suppurativa in a Chinese family.
AB  - Hidradenitis suppurativa (HS) is a chronic disease of follicular occlusion. It
      involves the axilla, groin, perianal and perineal regions, and is characterized
      by recurrent draining sinuses, skin abscesses and disfiguring scars. Loss-of
      function mutations in the genes encoding gamma-secretase have been identified as
      a cause of HS. We collected skin samples from three patients with HS from a
      Chinese family carrying a NCSTN mutation (c.1258C>T (p.Q420X)) and three
      unrelated healthy controls (HCs). Expression level of nicastrin in skin tissue
      and cultured keratinocytes and fibroblasts of patients and HCs was determined by
      real-time quantitative PCR and western blotting. We found that the mRNA and
      protein levels of nicastrin were significantly reduced in the whole skin,
      epidermis, dermis, and cultured keratinocytes and fibroblasts compared with HCs.
      Therefore, we conclude that haploinsufficiency of the NCSTN gene caused by the
      nonsense mutation c.1258C>T (p.Q420X) contributes to the occurrence of HS in this
      family. 

PMID- 26224165
TI  - Atmospheric Dispersal of Bioactive Streptomyces albidoflavus Strains Among
      Terrestrial and Marine Environments.
AB  - Members of the Streptomyces albidoflavus clade, identified by 16S rRNA sequencing
      and phylogenetic analyses, are widespread among predominant terrestrial lichens
      (Flavoparmelia caperata and Xanthoria parietina) and diverse intertidal and
      subtidal marine macroalgae, brown red and green (Phylum Heterokontophyta,
      Rhodophyta, and Chlorophyta) from the Cantabrian Cornice. In addition to these
      terrestrial and coastal temperate habitats, similar strains were also found to
      colonize deep-sea ecosystems and were isolated mainly from gorgonian and solitary
      corals and other invertebrates (Phylum Cnidaria, Annelida, Echinodermata,
      Arthropoda, and Porifera) living up to 4700-m depth and at a temperature of 2-4 
      degrees C in the submarine Aviles Canyon. Similar strains have been also
      repeatedly isolated from atmospheric precipitations (rain drops, snow, and
      hailstone) collected in the same area throughout a year observation time. These
      ubiquitous strains were found to be halotolerant, psychrotolerant, and
      barotolerant. Bioactive compounds with diverse antibiotic and cytotoxic
      activities produced by these strains were identified by high-performance liquid
      chromatography (HPLC) and database comparison. These include antibacterials
      (paulomycins A and B), antifungals (maltophilins), antifungals displaying also
      cytotoxic activities (antimycins and 6-epialteramides), and the antitumor
      compound fredericamycin. A hypothetical dispersion model is here proposed to
      explain the biogeographical distribution of S. albidoflavus strains in
      terrestrial, marine, and atmospheric environments.

PMID- 26224167
TI  - Efficacy of additional radiofrequency ablation after transcatheter arterial
      chemoembolization for intermediate hepatocellular carcinoma.
AB  - AIM: For intermediate hepatocellular carcinoma (HCC), transcatheter arterial
      chemoembolization (TACE) therapy is recommended in the guidelines as a
      monotherapy, although TACE is a non-curative therapy. The aims of the present
      study were to evaluate the efficacy of adding radiofrequency ablation (RFA) to
      TACE in patients with intermediate HCC, and to identify the factors that were
      associated with favorable survival in these patients. METHODS: Fifty-nine
      patients with intermediate HCC were enrolled in this retrospective study. Thirty
      nine patients were treated with TACE alone and 20 patients were treated with
      additional RFA after TACE. RESULTS: The recurrence-free survival rates at 0.5, 1
      and 2 years for the additional RFA group were 32%, 19% and 13%, respectively, and
      these were significantly higher than those of the TACE group (8%, 3% and 0%,
      respectively; log-rank test, P = 0.001). The cumulative survival rates of the
      additional RFA group were significantly higher than those of the TACE group (log
      rank test, P = 0.002), although this significant difference was not found in the
      subgroup of treatment naive patients because of small sample size. Multivariate
      analysis indicated male sex, lower total bilirubin, lower alpha-fetoprotein,
      lower des-gamma-carboxyprothrombin, newly recurrent HCC nodules within the last
      12 months and additional RFA as independent factors that were significantly
      associated with favorable overall survival. CONCLUSION: Additional RFA of nodules
      insufficiently treated by TACE is effective therapy for obtaining favorable
      disease-free survival in patients with intermediate HCC, and leads to better
      overall survival particularly in recurrent patients.

PMID- 26224164
TI  - Bacterial Diversity in Microbial Mats and Sediments from the Atacama Desert.
AB  - The Atacama Desert has extreme environmental conditions that allow the
      development of unique microbial communities. The present paper reports the
      bacterial diversity of microbial mats and sediments and its mineralogical
      components. Some physicochemical conditions of the water surrounding these
      ecosystems have also been studied trying to determine their influence on the
      diversity of these communities. In that way, mats and sediments distributed among
      different hypersaline lakes located in salt flats of the Atacama Desert were
      subjected to massive parallel sequencing of the V4 region of the 16S rRNA genes
      of Bacteria. A higher diversity in sediment than in mat samples have been found.
      Lakes that harbor microbial mats have higher salinity than lakes where mats are
      absent. Proteobacteria and/or Bacteroidetes are the major phyla represented in
      all samples. An interesting item is the finding of a low proportion or absence of
      Cyanobacteria sequences in the ecosystems studied, suggesting the possibility
      that other groups may be playing an essential role as primary producers in these
      extreme environments. Additionally, the large proportion of 16S rRNA gene
      sequences that could not be classified at the level of phylum indicates potential
      new phyla present in these ecosystems. 

PMID- 26224168
TI  - A radical approach for fluorescent turn 'on' detection, differentiation and
      bioimaging of methanol.
AB  - A simple Schiff base (RC) has been explored as a smart example of fluorescent
      material for the selective detection, differentiation and bioimaging of methanol.
      The nucleophilic attack of methanol on the cyclic control unit of RC leads to its
      opening and formation of a highly fluorescent moiety, RO. The RC displays a good
      sensitivity for MeOH with a detection limit of 0.042 wt% in water. 

PMID- 26224169
TI  - The Second Zambian National Tuberculosis Drug Resistance survey - a comparison of
      conventional and molecular methods.
AB  - OBJECTIVE: The prevalence of MDR-TB in Zambia was estimated to be 1.8% in 2001. A
      second drug resistance survey was conducted in 2008 to determine trends; the use
      of the Genotype MTBDRplus assay was applied to compare results to the gold
      standard. METHOD: A two-stage cluster sampling, with health facilities as primary
      sampling units. Processed sputum specimens were inoculated on solid media for
      culture; heat-inactivated bacterial suspensions from sputum samples were tested
      on a commercial line probe assay for the identification of rifampicin and
      isoniazid resistance. RESULTS: A total of 917 patients with TB were enrolled and
      883 (96.3%) analysed. A total of 574 (65%) had LJ results and 824 (93.3%) had
      results from MTBDRplus assay. The median age was 32, and 63.3% were males. MDR-TB
      according to LJ-based DST was 1.1% (CI 0.1-2.4) whereas according to MDTBDRplus
      assay was 1.6% (CI 0.6-2.6). Isoniazid monoresistance in new cases was 2.4% (CI
      0.613-4.26) based on LJ results and 5.0% (CI 3.2-6.7) based on the MTBDRplus; in
      retreatment cases, it was 4.4% (CI 0.3-8.6) and 2.40% (CI <0.1-5.1) on LJ and
      MTBDRplus, respectively. Rifampicin monoresistance in new cases was 0.1% (CI <0.1
      0.4) based on LJ and 0.6% (CI 0.01-1.1) based on the MTBDRplus; in retreatment
      cases, it was 0% (CI 0-3.8) and 1.8% (CI <0.1-4.0) on LJ and MTBDRplus,
      respectively. There were no XDR-TB cases found and no association between MDR-TB
      and HIV. CONCLUSION: There was no increase in MDR-TB prevalence in Zambia from
      2001 to 2008; results from the two methods were similar. Molecular methods were
      quicker and simpler to use.

PMID- 26224170
TI  - Conditions for obtaining polyvinyl alcohol/trisodium trimetaphosphate hydrogels
      as vitreous humor substitute.
AB  - Hydrogels are polymeric materials with numerous medical and biological
      applications because of their physicochemical properties. In this context, the
      conditions were defined for obtaining a hydrogel with characteristics similar to
      the vitreous humor using polyvinyl alcohol (PVA) and trisodium trimetaphosphate
      (STMP). The concentration of PVA (X1 ), PVA/STMP ratio (X2 ), and initial pH (X3
      ) were modified, and their effect was analyzed in terms of the refractive index
      (Y1 ), density (Y2 ), dynamic viscosity (Y3 ), and final pH (Y4 ). The results
      demonstrated that X1 interferes with Y1 , Y2 , and Y3 , and X2 interferes with Y2
      and Y3 . The best condition for obtaining a hydrogel with characteristics similar
      to the vitreous humor was 4.2586% PVA (wt/wt), STMP/PVA ratio of 1:6.8213
      (wt/wt), and initial pH of 9.424. DSC, ATR-FTIR, swelling degree, and AFM
      analysis confirmed the PVA reticulation with STMP. Furthermore, STMP increased
      the glass transition temperature and decreased the water uptake of ~50% of the
      hydrogels, which can be explained by the crosslinking of PVA chains. Infrared
      spectroscopy revealed a decrease of hydroxyl bonds and confirmed the reticulation
      between PVA and STMP. (c) 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 104B: 1386-1395, 2016.

PMID- 26224171
TI  - [Value of Heidelberg retinal tomography in glaucoma diagnostics].
AB  - BACKGROUND: The Heidelberg retinal tomography (HRT) is a technique that has been
      used for more than 20 years for glaucoma diagnostics and management. Many
      hundreds of scientific investigations have tested the reliability and accuracy of
      HRT for the early diagnosis of glaucoma and just as many studies can be found on
      the detection of progression in glaucoma. It is still one of the leading imaging
      systems for the detection and follow-up of glaucoma. Hardware and statistical
      methods implemented for progression detection have been regularly updated by the
      company and internationally known glaucoma specialists. METHODS: Besides the
      analysis of stereometric parameters and trend analyses, the primary method for
      assessing glaucomatous change using the HRT is the topographic change analysis
      (TCA), a technique that compares the variability within a baseline examination to
      that between baseline and follow-up examinations.Furthermore, the flicker
      comparison enables detection of small topographic changes over time. CONCLUSION:
      The use of HRT does not replace clinical examinations but facilitates the
      assessment and management of glaucoma depending on observer experience. This
      imaging method will still have a significant value in the future for glaucoma
      diagnostics, with a special emphasis on assessment of progression.

PMID- 26224172
TI  - [Investigation of color vision in acute unilateral optic neuritis using a web
      based color vision test].
AB  - BACKGROUND: In acute unilateral optic neuritis (ON) color vision defects combined
      with a decrease in visual acuity and contrast sensitivity frequently occur. This
      study investigated whether a web-based color vision test is a reliable detector
      of acquired color vision defects in ON and, if so, which charts are particularly
      suitable. METHODS: In 12 patients with acute unilateral ON, a web-based color
      vision test ( www.farbsehtest.de ) with 25 color plates (16 Velhagen/Broschmann
      and 9 Ishihara color plates) was performed. For each patient the affected eye was
      tested first and then the unaffected eye. RESULTS: The mean best-corrected
      distance visual acuity (BCDVA) in the ON eye was 0.36 +/- 0.20 and 1.0 +/- 0.1 in
      the contralateral eye. The number of incorrectly read plates correlated with the
      visual acuity. For the ON eye a total of 134 plates were correctly identified and
      166 plates were incorrectly identified, while for the disease-free fellow eye,
      276 plates were correctly identified and 24 plates were incorrectly identified.
      Both of the blue/yellow plates were identified correctly 14 times and incorrectly
      10 times using the ON eye and exclusively correctly (24 times) using the fellow
      eye. The Velhagen/Broschmann plates were incorrectly identified significantly
      more frequently in comparison with the Ishihara plates. In 4 out of 16
      Velhagen/Broschmann plates and 5 out of 9 Ishihara plates, no statistically
      significant differences between the ON eye and the fellow eye could be detected.
      CONCLUSION: The number of incorrectly identified plates correlated with a
      decrease in visual acuity. Red/green and blue/yellow plates were incorrectly
      identified significantly more frequently with the ON eye, while the
      Velhagen/Broschmann color plates were incorrectly identified significantly more
      frequently than the Ishihara color plates. Thus, under defined test conditions
      the web-based color vision test can also be used to detect acquired color vision
      defects, such as those caused by ON. Optimization of the test by altering the
      combination of plates may be a useful next step.

PMID- 26224173
TI  - [A 37-year-old man with peripheral retinal dystrophy].

PMID- 26224175
TI  - Appropriate use of oxygen in acute medicine.

PMID- 26224177
TI  - Making sense of alcohol consumption data in Australia.

PMID- 26224178
TI  - Precision medicine: are we there?

PMID- 26224179
TI  - Partnering with consumers: national standards and lessons from other countries.

PMID- 26224180
TI  - Medical tourism raises questions that highlight the need for care and caution.

PMID- 26224181
TI  - Acute HIV infection presenting as erythema multiforme in a 45-year-old
      heterosexual man.

PMID- 26224182
TI  - Effectiveness of a care bundle to reduce central line-associated bloodstream
      infections.

PMID- 26224183
TI  - Effectiveness of a care bundle to reduce central line-associated bloodstream
      infections.

PMID- 26224184
TI  - A new era in the treatment of multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease of the central nervous system
      with a multifactorial aetiology and highly variable natural history. A growing
      understanding of the immunopathogenesis of the condition has led to an expanding
      array of therapies for this previously untreatable disease. While a cure for MS
      remains elusive, the potential to reduce inflammatory disease activity by
      preventing relapses and minimising disease progression is achievable. The
      importance of early treatment in minimising long-term disability is increasingly
      recognised. Most of the newer, more effective therapies are associated with risks
      and practical problems that necessitate an active management strategy and
      continuous vigilance. While the initiation of these therapies is likely to remain
      the responsibility of neurologists, other specialist physicians and general
      practitioners will be involved in the identification and management of adverse
      effects. 

PMID- 26224185
TI  - Revalidation is not to be feared and can be achieved by continuous objective
      assessment.
AB  - Revalidation is defined by the International Association of Medical Regulatory
      Authorities as "the process by which doctors have to regularly show that they are
      up to date, and fit to practice medicine". In December 2012, the General Medical
      Council in the United Kingdom introduced revalidation processes that involve
      medical practitioners collecting a portfolio of evidence for assessment and
      appraisal by a "responsible officer". The responsible officer is usually the
      medical director of the hospital or group of primary care providers and reports
      directly to the General Medical Council on the fitness of the doctor to practice
      in their current role. The time taken to collect and analyse the portfolio and
      sources available are all contentious issues, along with the cost of the
      revalidation process. We propose that effective revalidation processes based on
      performance measurement would be cost-effective and, if correctly applied, could
      lead to significant cost savings in Australian health care. The driving force for
      an effective and efficient revalidation process should be the professional and
      ethical responsibility that each doctor has to their patients and to the society
      which has granted them the right to practice. 

PMID- 26224186
TI  - Actual availability of general practice appointments for mildly ill children.
AB  - OBJECTIVE: To determine actual availability and cost of general practitioner
      appointments for children with conditions of low acuity and low urgency, from the
      perspective of the child's family. DESIGN, PARTICIPANTS AND SETTING: A "secret
      shopper" method, whereby research assistants posing as parents seeking
      appointments for mildly ill children telephoned a random sample of 225 general
      practice clinics within three Melbourne Medicare Local catchments, which included
      urban, suburban and regional areas; the study was conducted between 1 August and
      30 September 2014. MAIN OUTCOME MEASURES: Availability of same-day appointments
      and time until appointment; bulk-billing status of the clinic and/or the
      potential cost of an appointment. RESULTS: High availability of appointments was
      found in all three catchment areas (range, 72%-81% of clinics contacted). About
      half (49%) had appointments available within 4 hours. Between 72% and 80% of
      clinics contacted in the three Medicare Local catchment areas offered bulk
      billing for paediatric appointments. CONCLUSION: There is extensive same-day new
      patient GP appointment availability for mildly ill children in the catchment
      areas of Melbourne studied. Further, as most of the available appointments are in
      clinics that bulk bill, financial access should not affect this availability.
      Increased paediatric presentations to emergency departments are not likely to be
      the result of limited GP availability. These findings provide an important base
      for developing data-driven policy approaches to the development and use of
      primary care.

PMID- 26224187
TI  - Use of complementary and alternative medicines for menopausal symptoms in
      Australian women aged 40-65 years.
AB  - OBJECTIVE: To document the prevalence of, and factors associated with, the use of
      complementary and alternative medicines (CAMs) for vasomotor symptoms (VMS) and
      other symptoms of menopause in Australian women aged 40-65 years. DESIGN, SETTING
      AND PARTICIPANTS: Cross-sectional questionnaire-based study of Australian women
      aged 40-65 years living independently in the community. Women able to complete a
      questionnaire in English were recruited by telephone between October 2013 and
      March 2014 from a large, representative, national, continually refreshed database
      derived from the electoral roll. MAIN OUTCOME MEASURES: Use of CAMs for VMS and
      other menopausal symptoms (eg, arthralgia, depression and sleep disturbance),
      assessed using the Menopause-Specific Quality of Life questionnaire. RESULTS: Of
      5850 women contacted, 2911 agreed to participate, and 2020 eligible women
      returned completed questionnaires (response rate, 34.53%). Most of the women were
      postmenopausal (54.90%), resided in metropolitan areas (62.70%) and were born in
      Australia (80.43%). The prevalence of use of CAMs for VMS was 13.22%.
      Phytoestrogens were most commonly used for VMS (6.29%), followed by evening
      primrose oil (3.91%) and ginseng (1.73%). Compared with premenopausal women,
      perimenopausal women (odds ratio [OR], 2.09; 95% CI, 1.42-3.06) and early
      postmenopausal women (OR, 1.83, 95% CI, 1.21-2.76) were more likely to use any
      CAM for VMS. The prevalence of use of CAMs for other symptoms was 32.23%; being
      postmenopausal and older were the factors associated with this use. CONCLUSIONS:
      Australian women at midlife are using CAMs that are known to be ineffective for
      managing VMS. Health care providers need to be more involved in guiding women in
      the treatment of VMS and other menopausal symptoms. More judicious use of
      supplements such as fish oil and glucosamine, particularly by older women, is
      needed until their efficacy and safety profiles are better understood.

PMID- 26224188
TI  - General practitioner understanding of abbreviations used in hospital discharge
      letters.
AB  - OBJECTIVES: To determine the incidence of abbreviation use in electronic hospital
      discharge letters (eDLs) and general practitioner understanding of abbreviations
      used in eDLsDesign, setting and participants: Retrospective audit of abbreviation
      use in 200 sequential eDLs was conducted at Nepean Hospital, Sydney, a tertiary
      referral centre, from 18 December to 31 December 2012. The 15 most commonly used
      abbreviations and five clinically important abbreviations were identified from
      the audit. A survey questionnaire using these abbreviations in context was then
      mailed to 240 GPs in the area covered by the Nepean Blue Mountains Local Health
      District to determine their understanding of these abbreviations. MAIN OUTCOME
      MEASURES: Number of abbreviations and frequency of their use in eDLs, and GPs'
      understanding of abbreviations used in the survey. RESULTS: 321 abbreviations
      were identified in the eDL audit; 48.6% were used only once. Fifty five per cent
      of GPs (132) responded to the survey. No individual abbreviation was correctly
      interpreted by all GPs. Six abbreviations were misinterpreted by more than a
      quarter of GPs. These were SNT (soft non-tender), TTE (transthoracic
      echocardiogram), EST (exercise stress test), NKDA (no known drug allergies), CTPA
      (computed tomography pulmonary angiogram), ORIF (open reduction and internal
      fixation). These abbreviations were interpreted incorrectly by 47.0% (62), 33.3%
      (44), 33.3% (44) 32.6% (43), 31.1% (41) and 28.0% (37) of GPs, respectively.
      CONCLUSION: Abbreviations used in hospital eDLs are not well understood by the
      GPs who receive them. This has potential to adversely affect patient care in the
      transition from hospital to community care.

PMID- 26224189
TI  - Splenic abscess complicating gastroenteritis due to Salmonella Virchow in an
      immunocompetent host.

PMID- 26224191
TI  - Splenic infarction after reversal of warfarin using Prothrombinex-VF in a patient
      with a mechanical aortic valve.

PMID- 26224192
TI  - Can I jump puddles alone?

PMID- 26224193
TI  - Some truths about the "low" childhood vaccination coverage in Sydney's eastern
      suburbs.

PMID- 26224194
TI  - I'm an alien, I'm a legal alien; I'm a French doctor in New South Wales!

PMID- 26224196
TI  - Elucidating the role of disorder and free-carrier recombination kinetics in
      CH3NH3PbI3 perovskite films.
AB  - Apart from broadband absorption of solar radiation, the performance of
      photovoltaic devices is governed by the density and mobility of photogenerated
      charge carriers. The latter parameters indicate how many free carriers move away
      from their origin, and how fast, before loss mechanisms such as carrier
      recombination occur. However, only lower bounds of these parameters are usually
      obtained. Here we independently determine both density and mobility of charge
      carriers in a perovskite film by the use of time-resolved terahertz spectroscopy.
      Our data reveal the modification of the free carrier response by strong
      backscattering expected from these heavily disordered perovskite films. The
      results for different phases and different temperatures show a change of kinetics
      from two-body recombination at room temperature to three-body recombination at
      low temperatures. Our results suggest that perovskite-based solar cells can
      perform well even at low temperatures as long as the three-body recombination has
      not become predominant. 

PMID- 26224197
TI  - Mode of birth and early postnatal psychological morbidity.
AB  - BACKGROUND: Postnatal depression affects the well-being of women and families.
      While several studies have shown an association between mode of birth and
      symptoms of postnatal depression, others have found no relationship. AIMS: To
      determine whether women who have instrumental or caesarean births report higher
      levels of poor coping, sleep or appetite disturbance, or relationship
      difficulties, than women who have vaginal births, at the time of Universal
      Postnatal Contact (7-10 days post-discharge). MATERIALS AND METHODS:
      Retrospective cohort study of term, singleton births from 1st January 2013 to
      31st December 2013 at a tertiary obstetric facility. Outcomes were compared for
      1816 women having vaginal births versus 1205 women having instrumental or
      caesarean births. RESULTS: When adjusted for confounders, no association could be
      demonstrated between mode of birth and reporting of any postnatal symptom of
      psychological morbidity. However, the model did demonstrate an association
      between reporting of symptoms and nulliparity (aOR 1.69 (1.08-2.63); P = 0.02),
      as well as having an unplanned pregnancy with a supportive partner (aOR 0.54
      (0.29-0.97); P = 0.04). CONCLUSIONS: Mode of birth does not appear to be
      associated with the reporting of symptoms of psychological morbidity in the early
      postnatal period. However, these symptoms may be associated with nulliparity and
      in the context of an unplanned pregnancy, a lack of partner support. These
      findings highlight the ongoing need for antenatal screening with respect to
      pregnancy intention and the presence of a social support system, to facilitate
      the implementation of interventions for women at risk of postnatal depression.

PMID- 26224198
TI  - Genome-wide construction of a series of designed segmental aneuploids in
      Saccharomyces cerevisiae.
AB  - Segmental aneuploidy can play an important role in environmental adaptation.
      However, study of segmental aneuploids is severely hampered by the difficulty of
      creating them in a designed fashion. Here, we describe a PCR-mediated chromosome
      duplication (PCDup) technology that enables the generation of segmental
      aneuploidy at any desired chromosomal region in Saccharomyces cerevisiae. We
      constructed multiple strains harboring 100 kb to 200 kb segmental duplications
      covering the whole of the S. cerevisiae genome. Interestingly, some segmental
      aneuploidies confer stress tolerance, such as to high temperature, ethanol and
      strong acids, while others induce cell lethality and stress sensitivity,
      presumably as result of the simultaneous increases in dosages of multiple genes.
      We suggest that our PCDup technology will accelerate studies into the phenotypic
      changes resulting from alteration of gene dosage balance of multiple genes and
      will provide new insights into the adaptive molecular mechanisms in the genome in
      segmental aneuploidy-derived human diseases.

PMID- 26224200
TI  - Undetermined stroke with an embolic pattern--a common phenotype with high early
      recurrence risk.
AB  - INTRODUCTION: Undetermined strokes with an embolic pattern (USEP) represent a
      common phenotype. We assessed their frequency and compared USEP with
      cardioembolic stroke with a known source and non-cardioembolic stroke etiology.
      METHODS: Study patients were 540 consecutive ischemic stroke patients admitted to
      Helsinki University Hospital with primary end-point of recurrent stroke in a 21
      month follow-up. Cox regression adjusting for CHA2DS2-VASc and anticoagulation
      estimated the risk of USEP on recurrent stroke. RESULTS: A total of 229 (42.4%)
      patients had a non-cardioembolic stroke etiology, 184 (34.1%) had a cardioembolic
      stroke with a known source, and 127 (23.5%) were classified as USEP. USEP
      patients had less diabetes and prior TIA, with more severe symptoms than the non
      cardioembolic stroke cases. They were younger, had fewer comorbidities, and less
      severe symptoms than the cardioembolic stroke patients. Cumulative risk of
      recurrent stroke was 10.0% (95% CI 4.1%-15.9%) for USEP, 5.0% (1.1%-8.9%) for
      cardioembolic strokes, and 5.0% (3.0%-7.0%) for non- cardioembolic strokes (P =
      0.089). USEP associated with a higher risk of recurrent stroke compared to non
      cardioembolic strokes (hazard ratio 2.36, 95% CI 1.02-5.47; P = 0.046) and
      cardioembolic stroke with a known source (1.83, 1.07-3.14; P = 0.028).
      CONCLUSIONS: Despite their younger age and more favorable risk factor profile
      compared with other phenotypes, USEP exhibited a high risk of stroke recurrence.

PMID- 26224199
TI  - Independent predictors of poor vitamin K antagonist control in venous
      thromboembolism patients. Data from the EINSTEIN-DVT and PE studies.
AB  - Vitamin K antagonists (VKA) are used to prevent recurrent disease in patients
      with venous thromboembolism (VTE). Their efficacy and safety depend on individual
      time in therapeutic range (iTTR) and variability of International Normalised
      Ratios (INR). We aimed to identify independent predictors of poor VKA control >
      28 days. In a prospective cohort of 3825 VTE patients, separate logistic
      regression analyses were performed to identify predictors of low iTTR (first
      quartile) and instability (iTTR <median and variability >median). Subsequently,
      the association between these predictors and clinical outcomes was investigated.
      Weight < 50 kg (odds ratio [OR]=1.89; 95 % confidence interval [CI] 1.03-3.49),
      active cancer at baseline (OR=1.52; CI1.05-2.19), secondary VTE (OR=1.42; CI1.20
      1.68), and INR < 2.0 at stop of double therapy (OR=1.35; CI1.09-1.67) were
      independent predictors of low iTTR. The first two were also predictive for
      instability (OR=1.96; CI1.06-3.63 and OR=1.95; CI1.36-2.80, respectively). ORs of
      early (<= 28 days) low iTTR and instability depended on VKA type. In
      acenocoumarol users, early low iTTR was an independent predictor of subsequent
      low iTTR (OR=1.92; CI1.31-2.80) and instability (OR=1.55; CI1.07-2.23). In
      warfarin users, early low iTTR (OR=1.36; CI1.09-1.69) and instability (OR=1.25;
      CI1.01-1.55) were additionally predictive for low iTTR, but only the latter was
      predictive for instability (OR=1.91; CI1.57-2.32). Many predictors of VKA control
      also predicted premature discontinuation, but only region was prognostic for
      clinical outcome. In conclusion, we identified several independent predictors of
      low iTTR and instability > 28 days, which showed some similarities but did not
      fully overlap. Early VKA control was of additional value for prediction of both,
      but had to be interpreted in the context of VKA type. 

PMID- 26224201
TI  - Age and gender variations of sleep in subjects without sleep disorders.
AB  - OBJECTIVE: Although sleep is a biomarker for general health and pathological
      conditions, its changes across age and gender are poorly understood. METHODS:
      Subjective evaluation of sleep was assessed by questionnaires in 5,064 subjects,
      and 2,966 were considered without sleep disorders. Objective evaluation was
      performed by polysomnography in 2,160 subjects, and 1,147 were considered without
      sleep disorders. Only subjects without sleep disorders were included (aged 40-80
      years). RESULTS: Aging was strongly associated with morning preference. Older
      subjects, especially women, complained less about sleepiness, and pathological
      sleepiness was significantly lower than in younger subjects. Self-reported sleep
      quality and daytime functioning improved with aging. Sleep latency increased with
      age in women, while sleep efficiency decreased with age in both genders. Deep
      slow-wave sleep decreased with age, but men were more affected. Spectral power
      densities within slow waves (< 5 Hz) and fast spindles (14-14.75 Hz) decreased,
      while theta-alpha (5-1 Hz) and beta (16.75-25 Hz) power in non-rapid eye movement
      sleep increased with aging. In REM sleep, aging was associated with a progressive
      decrease in delta (1.25-4.5 Hz) and increase in higher frequencies. CONCLUSIONS:
      Our findings indicate that sleep complaints should not be viewed as part of
      normal aging but should prompt the identification of underlying causes.

PMID- 26224202
TI  - Medicare outcomes have improved markedly over past two decades, study indicates.

PMID- 26224203
TI  - Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach
      for characterizing clobazam drug-drug interactions.
AB  - A metabolic mechanism-based characterization of antiepileptic drug-drug
      interactions (DDIs) with clobazam in patients with Lennox-Gastaut syndrome (LGS)
      was performed using a population pharmacokinetic (PPK) approach. To characterize
      potential DDIs with clobazam, pharmacokinetic (PK) data from 153 patients with
      LGS in study OV-1012 (NCT00518713) and 18 healthy participants in bioavailability
      study OV-1017 were pooled. Antiepileptic drugs (AEDs) were grouped based on their
      effects on the cytochrome P450 (CYP) isozymes responsible for the metabolism of
      clobazam and its metabolite, N-desmethylclobazam (N-CLB): CYP3A inducers
      (phenobarbital, phenytoin, and carbamazepine), CYP2C19 inducers (valproic acid,
      phenobarbital, phenytoin, and carbamazepine), or CYP2C19 inhibitors (felbamate,
      oxcarbazepine). CYP3A4 inducers-which did not affect the oral clearance of
      clobazam-significantly increased the formation of N-CLB by 9.4%, while CYP2C19
      inducers significantly increased the apparent elimination rate of N-CLB by 10.5%,
      resulting in a negligible net change in the PK of the active metabolite. CYP2C19
      inhibitors did not affect N-CLB elimination. Because concomitant use of AEDs that
      are either CYP450 inhibitors or inducers with clobazam in the treatment of LGS
      patients had negligible to no effect on clobazam PK in this study, dosage
      adjustments may not be required for clobazam in the presence of the AEDs
      investigated here. 

PMID- 26224204
TI  - IPSCs, a Promising Tool to Restore Muscle Atrophy.
AB  - Induced pluripotent stem cells (iPSCs) are a promising tool for regenerative
      medicine in chronic conditions associated with muscle atrophy since iPSCs are
      easier to obtain, pose less ethical limitations and can better capture human
      genetic diversity compared with human embryonic stem cells. We highlight the
      potentiality of iPSCs for treating muscle-affecting conditions for which no
      effective cure is yet available, notably aging sarcopenia and inherited
      neurometabolic conditions. J. Cell. Physiol. 231: 259-260, 2016. (c) 2015 Wiley
      Periodicals, Inc. 

PMID- 26224206
TI  - Augmenting the Deliberative Method for Ranking Risks.
AB  - The Department of Homeland Security (DHS) characterized and prioritized the
      physical cross-border threats and hazards to the nation stemming from terrorism,
      market-driven illicit flows of people and goods (illegal immigration, narcotics,
      funds, counterfeits, and weaponry), and other nonmarket concerns (movement of
      diseases, pests, and invasive species). These threats and hazards pose a wide
      diversity of consequences with very different combinations of magnitudes and
      likelihoods, making it very challenging to prioritize them. This article presents
      the approach that was used at DHS to arrive at a consensus regarding the threats
      and hazards that stand out from the rest based on the overall risk they pose. Due
      to time constraints for the decision analysis, it was not feasible to apply
      multiattribute methodologies like multiattribute utility theory or the analytic
      hierarchy process. Using a holistic approach was considered, such as the
      deliberative method for ranking risks first published in this journal. However,
      an ordinal ranking alone does not indicate relative or absolute magnitude
      differences among the risks. Therefore, the use of the deliberative method for
      ranking risks is not sufficient for deciding whether there is a material
      difference between the top-ranked and bottom-ranked risks, let alone deciding
      what the stand-out risks are. To address this limitation of ordinal rankings, the
      deliberative method for ranking risks was augmented by adding an additional step
      to transform the ordinal ranking into a ratio scale ranking. This additional step
      enabled the selection of stand-out risks to help prioritize further analysis. 

PMID- 26224205
TI  - Leveraging Cancer Therapeutics for the HIV Cure Agenda: Current Status and Future
      Directions.
AB  - Despite effective antiretroviral therapy (ART) and undetectable HIV RNA in the
      plasma, latent replication-competent HIV persists indefinitely in long-lived
      cells. Cessation of ART results in rebound of HIV from these persistent
      reservoirs. While this was thought to be an insurmountable obstacle to viral
      eradication, recent cases suggest otherwise. To date one patient has been "cured"
      of HIV and several others have been able to interrupt ART without viral rebound
      for prolonged periods. These events have sparked renewed interest in developing
      strategies that will allow eradication of HIV in infected individuals. We review
      the current knowledge of HIV latency and the viral reservoir, describe the
      potential utility of emerging cancer therapeutics in HIV cure research with an
      emphasis on pathways implicated in reservoir persistence, and outline
      opportunities and challenges in the context of the current clinical trial and
      regulatory environment.

PMID- 26224207
TI  - Roles of Carbonic Anhydrase IX in Development of Pancreatic Cancer.
AB  - The aim of this study was to study the effects of carbonic anhydrase IX (CA IX)
      towards the invasion and metastasis of pancreatic cancer. The expressions of CA
      IX in 58 cases of pancreatic cancer and paired paracancerous normal tissues,
      obtained from 2005 to 2012 in the first Affiliated Hospital of China Medical
      University, were detected, as well as its expressions in different pancreatic
      cancer cell lines, aiming to detect the impacts of CA IX silencing towards the
      invasion and metastasis of pancreatic cancer cells. The CA IX expressions in 58
      pancreatic cancer cases were higher than those in the paired paracancerous normal
      tissues (P < 0.01), and positively correlated with the tumor size and the UICC
      staging UICC (P < 0.05), the multivariate analysis showed that the high
      expression of CA IX was the independent risk factor towards the prognosis of
      pancreatic cancer (P < 0.05). The CA IX was highly expressed in AxPC-1 and
      Miapaca-2, and the interference effects were significant. CA IX silencing could
      significantly inhibit the invasion and metastasis of AxPC-1 and Miapaca. We
      support a pro-tumor role of CA IX in the development and progression of
      pancreatic cancer.

PMID- 26224208
TI  - Combination of granulocyte colony-stimulating factor and CXCR4 antagonist AMD3100
      for effective harvest of endothelial progenitor cells from peripheral blood and
      in vitro formation of primitive endothelial networks.
AB  - Endothelial progenitor cells (EPC) derived from the circulation may be used to
      enhance neovascularization. Since the combination of granulocyte colony
      stimulating factor (GCSF) and CXCR4 antagonist AMD3100 efficiently mobilizes
      hematopoietic stem cells into peripheral circulation, it may increase the pool of
      endogenously circulating EPC. We tested this hypothesis by administering GCSF and
      AMD3100 to adult rabbits and rats, isolating mononuclear cells from peripheral
      blood by Ficoll density gradient centrifugation, and characterizing the blood
      derived EPC based on morphology, immunophenotyping, gene expression and other
      functional analyses. These EPC showed clonal growth similar to that of human
      umbilical vein endothelial cells when cultured in complete EGM-2 medium on
      collagen I-precoated culture plates. The EPC exhibited a typical cobblestone-like
      morphology and were relatively homogeneous by the third passage. The cells
      expressed the typical endothelial marker CD31 based on flow cytometry and
      fluorescence microscopy, formed capillary-like structures when cultured in
      Matrigel, internalized DiI-acetylated low-density lipoprotein, bound Ulex
      europaeus agglutinin-1, and expressed CD31 and several other endothelial markers
      (VEGFR2, VE-cadherin, Tie-2, eNOS, vWF) at significantly higher levels than bone
      marrow-derived mesenchymal stem cells. These results suggest that the combination
      of GCSF and AMD3100 can efficiently release stem cells into peripheral
      circulation and generate EPC that show the desired morphological,
      immunophenotypic and functional characteristics. This minimally invasive approach
      may be useful for autologous cell transplantation for postnatal neovasculogenesis
      and tissue repair.

PMID- 26224209
TI  - Medical training in Greece: A crisis in progress.
AB  - OBJECTIVES: We sought to evaluate the opinions of medical students and graduates
      regarding the quality of medical education in Greece. METHODS: Two online
      questionnaires concerning the undergraduate medical education and specialty
      training respectively were distributed. RESULTS: Regarding the quality of
      undergraduate medical education, 52.1% of participants replied favorably while
      clinical training was found satisfactory by 45.1. Dissatisfaction rates with
      research opportunities and support from tutors reached 88.4 and 83.3%,
      respectively. The majority (75.3%) supported the introduction of examinations for
      commencing specialty training. 52.3% of physicians were satisfied with the
      quality of specialty training. The most common complaint was the absence of a
      formal educational program. 67.2% of participants were dissatisfied with working
      conditions during their specialty training, with 70.1% working >60 h per week.
      Physicians practicing medical specialties were more satisfied with the quality of
      specialty training than those practicing surgical specialties (odds ratio: 1.43;
      95% confidence limits: 1.09-1.87) and were less likely to work for >60 h per week
      (odds ratio: 0.66; 95% confidence limits: 0.48-0.9). CONCLUSION: Opinions
      expressed in this survey highlight the need for reforming medical education in
      Greece.

PMID- 26224210
TI  - Community-acquired pneumonia: An overview.
AB  - Community-acquired pneumonia is still a significant cause of morbidity and
      mortality and is often misdiagnosed and inappropriately treated. Although it can
      be caused by a wide variety of micro-organisms, the pneumococcus, atypicals, such
      as Mycoplasma pneumoniae and Chlamydophila pneumoniae, Staphylococcus aureus and
      certain Gram-negative rods are the usual pathogens encountered. The site-of-care
      decision is critical in determining the site and type of care as well as the
      extent of diagnostic workup. Antimicrobial therapy should be started as soon as
      possible particularly in those requiring admission to hospital, but typically the
      physician does not know with any degree of certainty the identity of the
      etiologic pathogen. A number of national guidelines have been published to help
      the physician with this choice. The initial drug(s) can be modified if necessary
      if the pathogen and its antimicrobial susceptibility pattern becomes known.
      Adjunctive therapy such as pressors and fluid replacement are of value and
      macrolides appear to help as well, likely secondary to their immunomodulatory
      effects. Recent data also suggest a role for steroids. 

PMID- 26224211
TI  - Tunable Keplerate Type-Cluster "Mo132 " Cavity with Dicarboxylate Anions.
AB  - The internal functionalization of the Keplerate-type capsule Mo132 has been
      carried out by ligand exchange leading to the formation of glutarate and
      succinate containing species isolated as ammonium or dimethylammonium salts.
      Solution NMR analysis is consistent with asymmetric inner dicarboxylate ions
      containing one carboxylato group grafted onto the inner side of the spheroidal
      inorganic shell while the second hangs toward the center of the cavity. Such a
      disposition has been confirmed by the single-crystal X-ray diffraction analysis
      of the glutarate containing {Mo132 } species. A detailed NMR solution study of
      the ligand-exchange process allowed determining the binding constant KL of
      acetate (AcO(-) ), succinate (HSucc(-) ) or glutarate (HGlu(-) ) ligands at the
      30 inner coordinating sites, which vary such as K AcO -<K HGlu -<K HSucc -
      supported by the associated thermodynamic parameters Deltar S* and Deltar H*.
      Such a variation is mainly explained by a positive entropic gain attenuated by
      unfavorable steric effect. Furthermore, these results are completed by (1) H DOSY
      and (1) H EXSY NMR experiments which are in agreement with bulky guests firmly
      trapped within the cavity. At last, variable temperature (1) H NMR study below
      290 K revealed a striking line broadening occurring abruptly within a 5 K range.
      Such an effect appears closely related to the presence of the ammonium cations
      suspected to be present within the cavity and then has been interpreted as an
      inner-phase transition leading to a frozen state. 

PMID- 26224212
TI  - Effect of rosiglitazone on asymmetric dimethylarginine metabolism in
      thioacetamide-induced acute liver injury.
AB  - Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase
      inhibitor, is metabolized in the liver by dimethylarginine dimethylaminohydrolase
      (DDAH). We aimed to investigate the effect of rosiglitazone, a peroxysome
      proliferator-activated receptor-gamma (PPAR-gamma) agonist, on ADMA metabolism in
      acute liver injury. Male Sprague Dawley rats were injected thioacetamide (TAA;
      500mgkg(-1)) intraperitoneally in order to induce acute liver injury. ADMA, SDMA
      and arginine levels were determined in plasma by the HPLC. Liver DDAH activity
      and malondialdehyde (MDA) levels were measured by spectrophotometric procedures.
      TAA injection caused marked increases in ALT and AST activities. Plasma ADMA
      levels were increased, while arginine levels and arginine/ADMA ratio were
      decreased. Liver DDAH activity was significantly diminished and MDA levels were
      elevated. In another group of animals which were treated with a PPAR-gamma
      agonist (rosiglitazone, 5mgkg(-1)) daily via gastric intubation for a week prior
      to TAA injection, significant recoveries in DDAH activity and antioxidant status
      were observed when compared with solely TAA-injected animals. Rosiglitazone
      pretreatment improved the plasma arginine/ADMA ratio. Our findings indicated that
      PPAR-gamma agonist rosiglitazone beneficially influenced hepatic metabolism of
      ADMA in TAA-induced acute liver damage. 

PMID- 26224215
TI  - Transport efficiency through uniformity: organization of veins and stomata in
      angiosperm leaves.
AB  - Leaves of vascular plants use specific tissues to irrigate the lamina (veins) and
      to regulate water loss (stomata), to approach homeostasis in leaf hydration
      during photosynthesis. As both tissues come with attendant costs, it would be
      expected that the synthesis and spacing of leaf veins and stomata should be
      coordinated in a way that maximizes benefit to the plant. We propose an
      innovative geoprocessing method based on image editing and a geographic
      information system to study the quantitative relationships between vein and
      stomatal spatial patterns on leaves collected from 31 angiosperm species from
      different biomes. The number of stomata within each areole was linearly related
      to the length of the looping vein contour. As a consequence of the presence of
      free-ending veinlets, the minimum mean distance of stomata from the nearest veins
      was invariant with areole size in most of the species, and species with smaller
      distances carried a higher density of stomata. Uniformity of spatial patterning
      was consistent within leaves and species. Our results demonstrate the existence
      of an optimal spatial organization of veins and stomata, and suggest their
      interplay as a key feature for achieving a constant mesophyll hydraulic
      resistance throughout the leaf. 

PMID- 26224214
TI  - Asymmetry in structure of the eggshell in Osmylus fulvicephalus (Neuroptera:
      Osmylidae): an exceptional case of breaking symmetry during neuropteran
      oogenesis.
AB  - Ovaries of neuropterans are of meroistic-polytrophic type. The ovarian tubes, the
      ovarioles, are divided into two major parts: a germarium, comprised of newly
      formed germ cell clusters; and a vitellarium, housing linearly arranged ovarian
      follicles. Each ovarian follicle consists of the germ cell cluster diversified
      into different number of nurse cells, and the oocyte enclosed by follicular
      epithelium. In Osmylus fulvicephalus, a representative of Neuroptera, during
      consecutive stages of oogenesis, the follicular cells undergo a multistep process
      of diversification which leads to the appearance of several follicular cell
      subpopulations i.e., the main-body follicular cells, the stretched cells, the
      anterior centripetal cells, and posterior centripetal cells. The anterior
      centripetal cells occupy the anterior pole of the oocyte and in advanced
      oogenesis due to hypertrophy that transform into anterior fold cells. Initially,
      the anterior fold cells form a symmetric fold, but in advanced oogenesis, quite
      different from other neuropterans studied so far, they undergo uneven
      hypertrophic growth which results in breaking symmetry of the anterior fold that
      becomes shifted to the ventral side of the oocyte. Since the anterior fold cells
      participate in the production of the specialized chorion structure, the
      micropyle, asymmetric structure of the anterior fold, is reflected both in its
      asymmetric position and in the asymmetric construction of the micropyle. As a
      consequence of breaking symmetry of the anterior fold, Osmylus eggshell gains
      dorso-ventral polarity, which is unusual for neuropterans. 

PMID- 26224216
TI  - Working well? Studying the nursing workforce.

PMID- 26224213
TI  - p24 family proteins: key players in the regulation of trafficking along the
      secretory pathway.
AB  - p24 family proteins have been known for a long time, but their functions have
      remained elusive. However, they are emerging as essential regulators of protein
      trafficking along the secretory pathway, influencing the composition, structure,
      and function of different organelles in the pathway, especially the ER and the
      Golgi apparatus. In addition, they appear to modulate the transport of specific
      cargos, including GPI-anchored proteins, G-protein-coupled receptors, or K/HDEL
      ligands. As a consequence, they have been shown to play specific roles in
      signaling, development, insulin secretion, and the pathogenesis of Alzheimer's
      disease. The search of new putative ligands may open the way to discover new
      functions for this fascinating family of proteins. 

PMID- 26224217
TI  - Individual and contextual antecedents of workplace aggression in aged care nurses
      and certified nursing assistants.
AB  - Employees in aged care are at high risk of workplace aggression. Research rarely
      examines the individual and contextual antecedents of aggression for specific
      types of workers within these settings, such as nurses and certified nursing
      assistants (CNAs). The study aimed to explore characteristics of the job demands
      resources model (JD-R), negative affectivity (NA) and demographics related to
      workplace aggression for aged care workers. The survey study was based on 208
      nurses and 83 CNAs working within aged care. Data from each group were analysed
      separately using ordinal regressions. Both aged care nurses and CNAs reported
      high rates of bullying, external emotional abuse, threat of assault and physical
      assault. Elements of the JD-R model and individual characteristics were related
      to aggression types for both groups. Characteristics of the JD-R model, NA and
      demographics are important in understanding the antecedents of aggression
      observed among aged care workers. 

PMID- 26224218
TI  - The differential effects of fluency due to repetition and fluency due to color
      contrast on judgments of truth.
AB  - Two experiments contrast the effects of fluency due to repetition and fluency due
      to color contrast on judgments of truth, after participants learn to associate
      high levels of fluency with falseness (i.e., a reversal of the fluency-truth
      link). Experiment 1 shows that the interpretation of fluency as a sign of truth
      is harder to reverse when learning is promoted with repetition rather than with
      perceptual fluency. Experiment 2 shows that when color contrast and repetition
      are manipulated orthogonally, the reversal of the truth effect learned with color
      contrast does not generalize to repetition. These results suggest specificities
      in the processing experiences generated by different sources of fluency, and that
      their influences can be separated in contexts that allow the contrast of their
      distinctive features. We interpret and discuss these results in light of the
      research addressing the convergence vs. dissociation of the effects elicited by
      different fluency sources. 

PMID- 26224219
TI  - Social Stigma and Childbearing for Women Living With HIV/AIDS.
AB  - As more women become infected with HIV, the issue of childbearing becomes
      increasingly salient. A more nuanced understanding of women's situations is
      needed to provide high-quality and relevant services and support. We examined
      reproductive decision making among 20 women living with HIV through in-depth
      interviews. These women made decisions within situations of chaos, instability,
      and trauma, which often limited their ability to make truly informed choices
      about their lives and childbearing. Despite their HIV, many of the women wanted
      children, but experienced stigmatization related both to their HIV and to their
      decisions to have children. This stigmatization came from multiple sources,
      including health care providers, some of whom encouraged their patients to abort
      pregnancies because of their HIV. Participants, however, demonstrated resistance
      to stigmatization, through building supportive communities and developing
      trusting relationships with HIV providers. These results support the need for
      specialized HIV care for women of childbearing age. 

PMID- 26224220
TI  - "How Would We Deserve Better?" Rural-Urban Dichotomy in Health Seeking for the
      Chronically Ill Elderly in China.
AB  - As China's older adult population has rapidly increased, the attending increase
      in chronic disease poses serious concerns regarding disparities in medical care
      utilization for elders. Drawing on 48 semistructured interviews with elders with
      chronic conditions and their caregivers in China, this article analyzes two
      opposite patterns of health-seeking behavior in urban and rural areas. Presenting
      the findings as a relational model, we argue that the interplay between
      structures of medical care and cultural discourses about health and
      (un)worthiness generates different habitus as sets of practices and beliefs that
      facilitate or hinder elders' and their caregivers' decisions to engage with
      medical care. By demonstrating the Chinese state's social health insurance
      reform's failure to improve health-seeking behavior on the ground, our findings
      suggest that efforts to understand and promote health-seeking behavior need to
      address the intersections of structural and cultural factors. 

PMID- 26224221
TI  - Antenatal magnetic resonance imaging versus ultrasound for predicting neonatal
      macrosomia: a systematic review and meta-analysis.
AB  - BACKGROUND: Fetal macrosomia is associated with an increased risk of adverse
      maternal and neonatal outcomes. OBJECTIVES: To compare the accuracy of antenatal
      two-dimensional (2D) ultrasound, three-dimensional (3D) ultrasound, and magnetic
      resonance imaging (MRI) in predicting fetal macrosomia at birth. SEARCH STRATEGY:
      Medline (1966-2013), Embase, the Cochrane Library and Web of Knowledge. SELECTION
      CRITERIA: Cohort or diagnostic accuracy studies of women with a singleton
      pregnancy, who had third-trimester imaging to predict macrosomia (>4000 g, >4500
      g or >90th or >95th centile). DATA COLLECTION AND ANALYSIS: Two reviewers
      screened studies, performed data extraction and assessed methodological quality.
      The bivariate model was used to obtain summary sensitivities, specificities and
      likelihood ratios. MAIN RESULTS: Fifty-eight studies (34 367 pregnant women) were
      included. Most were poorly reported. Only one study assessed 3D ultrasound
      volumetry. For predicting birthweight >4000 g or >90th centile, the summary
      sensitivity for 2D ultrasound (Hadlock) estimated fetal weight (EFW) >90th
      centile or >4000 g (29 studies) was 0.56 (95% CI 0.49-0.61), 2D ultrasound
      abdominal circumference (AC) >35 cm (four studies) was 0.80 (95% confidence
      interval [95% CI] 0.69-0.87) and MRI EFW (three studies) was 0.93 (95% CI 0.76
      0.98). The summary specificities were 0.92 (95% CI 0.90-0.94), 0.86 (95% CI 0.74
      0.93) and 0.95 (95% CI 0.92-0.97), respectively. CONCLUSION: There is
      insufficient evidence to conclude that MRI EFW is more sensitive than 2D
      ultrasound AC (which is more sensitive than 2D EFW); although it was more
      specific. Further primary research is required before recommending MRI EFW for
      use in clinical practice. TWEETABLE ABSTRACT: Systematic review of antenatal
      imaging to predict macrosomia. MRI EFW is more sensitive than ultrasound EFW.

PMID- 26224222
TI  - Screening for lupus anticoagulants in patients treated with vitamin K
      antagonists.
AB  - INTRODUCTION: The dRVVT test for detecting lupus anticoagulants (LA) is difficult
      to interpret when patients are treated with vitamin K antagonists (VKA). METHODS:
      We performed LA testing in 33 VKA-treated patients with definite antiphospholipid
      syndrome (APS) and compared the results with 100 controls subjects not receiving
      VKA and 110 APL-negative patients anticoagulated for reasons other than APS.
      RESULTS: Compared with the dRVVT ratio before the initiation of VKA therapy, a
      higher cutoff value, defined as the 99th percentile, was established for VKA
      treated patients with INR values between 2.0 and 3.5. A dRVVT ratio of >1.7
      yielded a sensitivity of 81.3%, specificity of 99.1%, and positive and negative
      predictive values of 98.7% and 85.8%, respectively, for detecting LA. Cohen's
      kappa coefficient indicated good agreement for the dRVVT ratio obtained from
      testing with and without VKA treatment (kappa = 0.813; 95% CI: 0.773-0.853),
      which was higher (kappa = 0.941; 95% CI: 0.917-0.965) when the LA diagnosis was
      based on the results of both the dRVVT and a second test system (i.e., Mixcon-LA
      assay). CONCLUSIONS: Lupus anticoagulants testing in VKA-treated patients with
      APS according to current guidelines appears to be possible for the majority of
      patients without discontinuing anticoagulant therapy.

PMID- 26224223
TI  - Changes in ghrelin, leptin and pro-inflammatory cytokines after therapy in
      Obstructive Sleep Apnea Syndrome (OSAS) patients.
AB  - INTRODUCTION: The correlations between the levels of cytokines, apnea, and
      obesity are not well understood. The aim of this study was to investigate the
      relationship between sleep apnea, body mass index (BMI) and plasma levels of
      leptin, ghrelin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF
      alpha). MATERIALS AND METHODS: Levels of leptin, ghrelin, IL-6, and TNF-alpha
      were compared in 20 obese (BMI > 30 kg/m2) and 6 non-obese patients (BMI < 27
      kg/m2) with Obstructive Sleep Apnea Syndrome (OSAS), and in 13 obese and 11 non
      obese control subjects without OSAS. All patients were investigated with
      Polysomnography (PSG) and ENT examination with flexible endoscopy and Muller's
      maneuver. Twelve patients were treated with continuous positive airway pressure
      (CPAP) and 14 with surgery. Fasting leptin, ghrelin and cytokine levels were
      measured at baseline, 2 days and 6 months after initiation of CPAP treatment, and
      6 months after surgery. RESULTS: Leptin, ghrelin and cytokine levels did not
      change significantly from baseline after 2 days of CPAP. After 6 months of CPAP
      or surgery, leptin, IL-6, and TNF-alpha levels were decreased in all OSAS
      patients. No difference in ghrelin levels was observed. DISCUSSION: Elevated
      leptin levels are not determined by obesity alone, since they decreased with
      Apnea Hypopnea Index reduction. Higher pro-inflammatory cytokine basal levels
      observed in patients with OSAS were not correlated with BMI.

PMID- 26224224
TI  - Supraclavicular artery pedicled flap in reconstruction of pharyngocutaneous
      fitulas after total laryngectomy.
AB  - The aim of the study was to analyze the efficacy of treatment of closure of
      cutaneopharyngeal fistulas, following total laryngectomy, using a fasciocutaneous
      flap. In the group of 6 patients treated in years 2013-2014, in 4 (67%) patients
      the healing process was successful, in one patient complete flap necrosis was
      noted on the 6th day, in another patient a small cutaneopharyngeal fistula was
      recognized, which closed secondarily with no intervention. Flaps of this type,
      having a small risk of local complications at donor site and satisfactory
      functional and aesthetic results, may be an alternative form of flap to others
      used in the reconstruction of superficial deficits in the head and neck areas.

PMID- 26224225
TI  - Compensatory hypertrophy of the contralateral inferior turbinate in patients with
      unilateral nasal septal deviation. A computed tomography study.
AB  - INTRODUCTION: The compensatory hypertrophy of the inferior turbinate in patients
      with septal deviation to one of the nostrils is considered to protect the airways
      from the excess of air that could enter through the nostril and its potential
      negative effects such as dryness, alteration of air filtration, mucociliary flow,
      or lung involvement. MATERIALS AND METHODS: A prospective, longitudinal, non
      randomized study. Patients were divided in two groups: 10 consecutive patients,
      with nasal septal deviation and compensatory hypertrophy of the inferior
      turbinate in the contralateral nasal cavity (10 non-hypertrophied turbinates as
      control and 10 contralateral hypertrophied turbinates as study cases), and the
      second group with 5 patients without any nasal pathology (10 turbinates without
      any obvious pathology). In both groups CT scans of the nasal region were
      performed. A comparison of patients with nasal septal deviation with compensatory
      hypertrophy of the inferior turbinate in the contralateral nasal cavity and with
      non-pathological inferior turbinate was carried out. RESULTS: When analyzing the
      groups of patients with septal deviation, the contralateral hypertrophied
      turbinate and the non-hypertrophied turbinate side, we found a significant
      hypertrophy in the anterior portion of the inferior turbinate, at the level of
      the medial mucosa (P = 0.002) and bone (P = 0.001) in the group of patients with
      contralateral hypertrophied turbinate. However, when we compared the
      contralateral hypertrophic turbinate with the turbinate of patients without
      septal deviation, we found a significant difference in all volumes of the medial
      and lateral mucosa and the bone portion (P = 0.001, P = 0.005). CONCLUSION:
      Surgical correction of the nasal septum and lateralization or reduction of the
      volume of the inferior turbinate (which may include the medial mucosa, head or
      part of the bone) is necessary in order to improve air passage into the nasal
      valve.

PMID- 26224226
TI  - How useful is ultrasound in the assessment of local advancement of laryngeal
      cancer?
AB  - AIM: The aim of the presented study was to examine the possibility of assessing
      the advancement of laryngeal cancer by ultrasound (USG) in patients qualified for
      laryngectomy. MATERIAL AND METHODS: Ultrasound examination of the larynx was
      performed in 25 patients before the planned surgery. The staging of larynx tumor
      was evaluated according to the guidelines of the American Joint Committee on
      Cancer (AJCC). Laryngectomy was performed eventually in 22 patients. The results
      of histopathological examination of the excised larynx and lymph nodes were
      compared with the results obtained by ultrasound examination performed prior to
      surgery using McNemar test to estimate the accuracy, sensitivity, and specificity
      of the method. RESULTS: The evaluation of tumor location with ultrasound was
      appropriate in all patients in the presented study. The accuracy of staging tumor
      advancement was 81% for USG (18/22). The sensitivity and specificity of
      ultrasound in detecting infiltration of paraglottic space was 91.7% and 83.3%,
      respectively, and in detecting subglottic infiltration - 100% and 95.2%,
      respectively. The sensitivity of ultrasound in the assessment of preepiglotic
      space infiltration and invasion of the laryngeal cartilage was 75% and
      specificity - 100% and 88.9%, respectively. The sensitivity of ultrasound in the
      assessment of extralaryngeal infiltration was 50% and the specificity 100%.
      CONCLUSIONS: Ultrasound can provide a valuable complement to laryngoscopy and
      tomography in patients with laryngeal cancer. It enables the real-time evaluation
      of cancer advancement before planned surgery. Moreover, it can also be used in
      screening.

PMID- 26224227
TI  - US in preoperative evaluation of parotid gland neoplasms.
AB  - Salivary gland neoplasms account for only 3% of all tumors of the head and neck
      area, but as they represent a wide variety of histological types, they are a big
      diagnostic challenge. The cornerstone of salivary gland neoplasm treatment, both
      for the benign and malignant lesions, is surgery. The main goal of the therapy is
      not only to achieve complete surgical tumor resection, but also to preserve
      adjacent structures (facial nerve, parapharyngeal space structures).
      Ultrasonography is an examination commonly used in the preoperative diagnosis of
      the lesions localized within salivary glands. Very often it is the only
      diagnostic imaging method used in these cases. The aim of the study was to
      establish diagnostic value of US examination and its parameters for the
      assessment of parotid gland tumors. A prospective study was performed on a group
      of 51 patients with parotid gland neoplasms, who over a period of 3 years
      underwent surgery in Otolaryngology and Laryngological Oncology Department with
      Craniomaxillofacial Surgery Department of Central Clinical Hospital of Ministry
      of Defence in Warsaw. All the included patients underwent US examination in the
      preoperative period. The parameters selected for the assessment were: ill-defined
      tumor margins, tumor vascularity and the presence of enlarged regional lymph
      nodes. The results of imaging examination were compared to the final diagnosis
      based on pathological examination of the surgical specimen. The parameters of the
      US examination such as sensitivity, specificity, positive predictive value (PPV),
      and negative predictive value (NPV) for the evaluation of parotid gland tumors
      were established based on the examination results. An analysis was performed and
      ill-defined parotid tumor margins turned out to be a US parameter with higher
      diagnostic value for differentiating benign and malignant lesions than increased
      tumor vascularity. The presence of enlarged regional lymph nodes with blurred
      echostructure on the US examination had little value for differentiating lesions.
      The sensitivity of the US examination in terms of detecting malignant parotid
      gland neoplasms increased significantly in the setting of simultaneous assessment
      of several parameters.

PMID- 26224228
TI  - Stylalgia: A Missed Diagnosis.
AB  - AIMS AND OBJECTIVE: To study the occurrence of stylalgia in patients presenting
      with pain in the head and neck region and appropriate management options.
      MATERIALS AND METHODS: This was a hospital-based study. This study analyzed
      prospectively patients who presented to the otolaryngology outpatient department
      with complaints of throat pain, globus, neck pain, facial pain, odynophagia,
      throat pain associated with earache, and neuralgic pain, and were diagnosed with
      stylalgia and managed with styloidectomy or subjected to medical treatment.
      RESULTS: Out of 20 patients (4 males and 16 females), 14 patients became symptom
      free, while 6 patients experienced relief of symptoms. There was no worsening of
      symptoms in any of the patients. CONCLUSION: The incidence of Stylalgia is higher
      in a female population. Elective management of patients after assessing the
      response to treatment, and then offering surgical management is of value for
      adequate patient care, prevention of unnecessarily delayed diagnosis and
      appropriate treatment.

PMID- 26224230
TI  - Tinea capitis in Campania, Italy: a 9-year retrospective study.
AB  - AIM: The present work was carried out to study the prevalence of Tinea capitis
      (TC) in Campania over a 9-year period and also to delineate the prevalence of the
      causative fungus responsible and the clinical forms of tinea capitis. METHODS:
      This retrospective study included all the cases of TC occurring between January
      2004 and December 2012 to the Mycology Laboratory at the University of Naples
      "Federico II" and mycologically confirmed. Samples for potassium hydroxide 20%
      mounts and fungal cultures were collected. Sabouraud dextrose agar were
      inoculated with the samples. RESULTS: TC was diagnosed by direct microscopy and
      culture in 143 patients. TC was found to be most common in the group including
      patients aged between 1-18 years; 13% of patients were over 18 years old. Non
      inflammatory clinical forms were the most common type (80.4%). M. canis was the
      dermatophyte most frequently isolated (64.1%). Microscopic examination revealed
      an ectothrix pattern of hair invasion to be more common (72% cases). CONCLUSION:
      TC was clinical and mycologically diagnosed in 143 patients. It was prevalent in
      patients aged 1-18 years old; 73.2% of adults affected by TC had possible risk
      factors and in these patients TC often presented in atypical forms; atypical
      forms were also observed in children. M. canis was the most common dermatophyte
      species isolated in children, T. rubrum in adults. We noticed a significant
      increase of anthropophilic dermatophytes possibly linked to the immigration from
      African countries. For the diagnosis of TC, mycological examinations are
      essential.

PMID- 26224231
TI  - Merkel cell carcinoma: a review.
AB  - Merkel cell carcinoma (MCC) is a rare aggressive primary cutaneous carcinoma with
      high mortality and rising incidence. The exact etiology of MCC remains unclear,
      but it is likely multifactorial with many factors playing a role, among these,
      ultraviolet radiation, immunosuppression, and recently, Merkel cell polyomavirus.
      Clinically MCC appears as an asymptomatic, firm, skin colored, sometimes reddish
      blue, dome-shaped papule or plaque or subcutaneous nodule typically localized on
      the head and neck region that has grown rapidly. As its clinical presentation is
      generally non specific, the diagnosis relies on histological and
      immunohistochemical findings. Once diagnosis is established, adequate staging
      requires evaluation of regional and distant metastases. Treatment is based on
      multidisciplinary management although optimal therapy is controversial, at least
      in part due to a lack of quality data. Aggressive surgery frequently associated
      with adjuvant radiotherapy is used to improve the rates of locoregional
      recurrence and overall survival as well. Future targeted therapies may open new
      perspectives for the treatment of patients although high-quality, multicentre and
      randomized studies are needed. In this article, the current knowledge about MCC
      is reviewed and discussed. 

PMID- 26224232
TI  - Effect of an antioxydant cream versus placebo in patients with vitiligo in
      association with excimer laser. A pilot randomized, investigator-blinded, and
      half-side comparison trial.
AB  - The aim of this study was to evaluate the combined effect of excimer laser and a
      topical antioxidant in the treatment for vitiligo. The study was conducted in a
      single blinded design on 10 vitiligo patients with symmetrical vitiligo lesions
      treated with the active antioxidant or a placebo that were irradiated with an
      excimer laser. Results have shown that the lesions treated with the active cream
      achieved earlier regimentation compared to the placebo. The use of a cream
      containing antioxidants may improve the results of excimer laser treatment in
      patients with vitiligo. 

PMID- 26224233
TI  - Cyclosporine A microemulsion in dermatological practice: is oral solution better
      tolerated than soft gelatin capsules?

PMID- 26224234
TI  - Outbreak of onychomadesis in a nursery: which diagnosis?

PMID- 26224235
TI  - Two cases of successful efavirenz desensitization in patients with several anti
      HIV drugs hypersensitivities.

PMID- 26224236
TI  - Tattoo: an immune-marked area.

PMID- 26224237
TI  - Acne infantum case presentation: how difficult is it to treat? Is it an alarm
      signal for an underlying endocrinological disorder?

PMID- 26224238
TI  - A case of an uncommonly rapid growing, therapy resistant squamous cell carcinoma
      of the nose in an immunocompetent patient.

PMID- 26224239
TI  - Tricholemmoma, sebaceoma, syringocystadenoma papilliferum, basal cell carcinoma,
      trichilemmal cyst arising within a nevus sebaceous.

PMID- 26224240
TI  - A solitary atrophic lesion of the left arm.

PMID- 26224241
TI  - YouTubeTM as a Source of Instructional Videos on Bowel Preparation: a Content
      Analysis.
AB  - Instructional videos on bowel preparation have been shown to improve bowel
      preparation scores during colonoscopy. YouTubeTM is one of the most frequently
      visited website on the internet and contains videos on bowel preparation. In an
      era where patients are increasingly turning to social media for guidance on their
      health, the content of these videos merits further investigation. We assessed the
      content of bowel preparation videos available on YouTubeTM to determine the
      proportion of YouTubeTM videos on bowel preparation that are high-content videos
      and the characteristics of these videos. YouTubeTM videos were assessed for the
      following content: (1) definition of bowel preparation, (2) importance of bowel
      preparation, (3) instructions on home medications, (4) name of bowel cleansing
      agent (BCA), (5) instructions on when to start taking BCA, (6) instructions on
      volume and frequency of BCA intake, (7) diet instructions, (8) instructions on
      fluid intake, (9) adverse events associated with BCA, and (10) rectal effluent.
      Each content parameter was given 1 point for a total of 10 points. Videos with
      >=5 points were considered by our group to be high-content videos. Videos with
      <=4 points were considered low-content videos. Forty-nine (59 %) videos were low
      content videos while 34 (41 %) were high-content videos. There was no association
      between number of views, number of comments, thumbs up, thumbs down or engagement
      score, and videos deemed high-content. Multiple regression analysis revealed
      bowel preparation videos on YouTubeTM with length >4 minutes and non-patient
      authorship to be associated with high-content videos.

PMID- 26224242
TI  - Virtual Learning Environment in Continuing Education for Nursing in Oncology: an
      Experimental Study.
AB  - Nurses working in oncology require continuing education and nowadays distance
      education is a possibility. To compare learning outcomes of the professionals
      participating in classroom learning versus distance learning; describing the
      sociodemographic characteristics and digital fluency of participants; comparing
      learning outcomes with independent variables; assessing the adequacy of
      educational practices in Virtual Environment Moodle Learning through the
      constructivist online learning environment survey. An experimental, randomized
      controlled study; conducted at the A C Camargo Cancer Center, located in Sao
      Paulo, SP, Brazil. The study included 97 nurses, with average training of 1 to 2
      years. A control group (n = 44) had face to face training and the experiment
      group (n = 53) had training by distance learning, both with identical program
      content. The dependent variable was the result of learning, measured by applying
      a pre-assessment questionnaire and post-intervention for both groups. The
      sociodemographic and digital fluency data were uniform among the groups. The
      performance of both groups was statistically significant (p 0.005), and the
      control group had a greater advantage (40.4 %). Distance education has proven to
      be an effective alternative for training nurses, especially when they have more
      complex knowledge, more experience in the area and institutional time. Distance
      Education may be a possibility for the training of nurses for work in oncology.
      The association of age, training time and the institution, and the experience in
      Oncology interfered in the performance of both groups.

PMID- 26224243
TI  - The dragon in the cockpit: how western aviation concepts conflicts with chinese
      value systems.

PMID- 26224244
TI  - Ticagrelor, prasugrel, or clopidogrel in ST-segment elevation myocardial
      infarction: which one to choose?
AB  - INTRODUCTION: Clopidogrel, prasugrel, and ticagrelor are the currently available
      oral P2Y12 inhibitors for the treatment of ST-segment elevation myocardial
      infarction (STEMI), in association with aspirin. These agents bind the P2Y12
      platelet receptor and thus inhibit platelet aggregation. Large randomized
      clinical trials have provided efficacy and safety data on P2Y12 inhibitors in
      STEMI patients. AREAS COVERED: This review focuses on key pharmacologic and
      clinical aspects of clopidogrel, prasugrel, and ticagrelor, highlighting their
      differences. Results from the main clinical trials are discussed, as well as the
      current STEMI guideline recommendations, to help inform agent selection for
      patients presenting with STEMI. EXPERT OPINION: Clinical trials studying newer
      P2Y12 inhibitors with increased potency have shown further reduction of
      cardiovascular events compared with clopidogrel, therefore suggesting the use of
      ticagrelor or prasugrel as a first-line agent for STEMI treatment. There are
      still clinical situations - such as fibrinolysis, high risk of bleeding, use of
      oral anticoagulant, and financial hurdles - in which clopidogrel maintains a role
      in the treatment of STEMI.

PMID- 26224245
TI  - Methionine sulfoxide reductase A (MsrA) contributes to Salmonella Typhimurium
      survival against oxidative attack of neutrophils.
AB  - Salmonella Typhimurium (ST) must evade neutrophil assault for infection
      establishment in the host. Myeloperoxidase generated HOCl is the key
      antimicrobial agent produced by the neutrophils; and methionine (Met) residues
      are the primary targets of this oxidant. Oxidation of Mets leads to methionine
      sulfoxide (Met-SO) formation and consequently compromises the protein
      function(s). Methionine sulfoxide reductase A (MsrA) reductively repairs Met-SO
      to Mets. In this manner, MsrA maintains the function(s) of key proteins which are
      important for virulence of ST and enhance the survival of this bacterium under
      oxidative stress. We constructed msrA gene deletion strain (DeltamsrA). The
      primers located in the flanking regions to DeltamsrA gene amplified 850 and 300
      bp amplicons in ST and DeltamsrA strains, respectively. The DeltamsrA strain grew
      normally in in vitro broth culture. However, DeltamsrA strain showed high
      susceptibility (p<0.001) to very low concentrations of HOCl which was restored
      (at least in part) by plasmid based complementation. DeltamsrA strain was
      hypersensitive (than ST) to the granules isolated from neutrophils. Further, the
      DeltamsrA strain was significantly (p<0.05) more susceptible to neutrophil
      mediated killing.

PMID- 26224247
TI  - Antitumor and cytotoxic properties of a humanized antibody specific for the
      GM3(Neu5Gc) ganglioside.
AB  - Gangliosides are sialic acid-bearing glycosphingolipids expressed on all
      mammalian cell membranes, and participate in several cellular processes. During
      malignant transformation their expression changes, both at the quantitative and
      qualitative levels. Of particular interest is the overexpression by tumor cells
      of Neu5Gc-gangliosides, which are absent, or detected in trace amounts, in human
      normal cells. The GM3(Neu5Gc) ganglioside in particular has been detected in many
      human tumors, and it is considered one of the few tumor specific antigen. We
      previously demonstrated that a humanized antibody specific for this molecule,
      named 14F7hT, retained the binding and cytotoxic properties of the mouse
      antibody. In this work, we confirm that 14F7hT exerts a non-apoptotic cell death
      mechanism in vitro and shows its potent in vivo antitumor activity on a solid
      mouse myeloma model. Also, we demonstrate, in contrast to the murine counterpart,
      the capacity of this antibody to induce antibody-dependent cell-mediated
      cytotoxicity using human effector cells, which increases its potential for the
      treatment of GM3(Neu5Gc)-expressing human tumors. 

PMID- 26224246
TI  - Treg depletion attenuates irradiation-induced pulmonary fibrosis by reducing
      fibrocyte accumulation, inducing Th17 response, and shifting IFN-gamma, IL-12/IL
      4, IL-5 balance.
AB  - Irradiation-induced pulmonary fibrosis results from thoracic radiotherapy and
      severely limits radiotherapy approaches. CD4(+) CD25(+) FoxP3(+) regulatory T
      cells (Tregs) are involved in experimentally induced murine lung fibrosis.
      However, the precise contribution of Tregs to irradiation-induced pulmonary
      fibrosis still remains unclear. We have previously established the mouse model of
      irradiation-induced pulmonary fibrosis and observed an increased frequency of
      Tregs during the process. This study aimed to investigate the effects of Treg
      depletion on irradiation-induced pulmonary fibrosis and on fibrocyte, Th17 cell
      response and production of multiple cytokines in mice. Treg-depleted mice were
      generated by intraperitoneal injection with anti-CD25 mAb 2h after 20 Gy (60)CO
      gamma-ray thoracic irradiation and every 7 days thereafter. Pulmonary fibrosis
      was semi-quantitatively assessed using Masson's trichrome staining. The
      proportions of Tregs, fibrocyte and Th17 cells were detected by flow cytometry.
      Th1/Th2 cytokines were assessed by Luminex assays. We found that Treg depletion
      decelerated the process of irradiation-induced pulmonary fibrosis and hindered
      fibrocyte recruitment to the lung. In response to Treg depletion, the number of
      CD4(+) T lymphocytes and Th17 cells increased. Moreover, Th1/Th2 cytokine balance
      was disturbed into Th1 dominance upon Treg depletion. Our study demonstrates that
      Tregs are involved in irradiation-induced pulmonary fibrosis by promoting
      fibrocyte accumulation, attenuating Th17 response and regulating Th1/Th2 cytokine
      balance in the lung tissues, which suggests that Tregs may be therapeutically
      manipulated to decelerate the progression of irradiation-induced pulmonary
      fibrosis.

PMID- 26224248
TI  - Nuclear volume effects in equilibrium stable isotope fractionations of mercury,
      thallium and lead.
AB  - The nuclear volume effects (NVEs) of Hg, Tl and Pb isotope systems are
      investigated with careful evaluation on quantum relativistic effects via the
      Dirac's formalism of full-electron wave function. Equilibrium (202)Hg/(198)Hg,
      (205)Tl/(203)Tl, (207)Pb/(206)Pb and (208)Pb/(206)Pb isotope fractionations are
      found can be up to 3.610/00, 2.540/00, 1.480/00 and 3.720/00 at room temperature,
      respectively, larger than fractionations predicted by classical mass-dependent
      isotope fractionations theory. Moreover, the NVE can cause mass-independent
      fractionations (MIF) for odd-mass isotopes and even-mass isotopes. The plot of
      [formula in text] for Hg-bearing species falls into a straight line with the
      slope of 1.66, which is close to previous experimental results. For the first
      time, Pb(4+)-bearing species are found can enrich heavier Pb isotopes than Pb(2+)
      bearing species to a surprising extent, e.g., the enrichment can be up to
      4.340/00 in terms of (208)Pb/(206)Pb at room temperature, due to their NVEs are
      in opposite directions. In contrast, fractionations among Pb(2+)-bearing species
      are trivial. Therefore, the large Pb fractionation changes provide a potential
      new tracer for redox conditions in young and closed geologic systems. The
      magnitudes of NVE-driven even-mass MIFs of Pb isotopes (i.e., [formula in text])
      and odd-mass MIFs (i.e., [formula in text) are almost the same but with opposite
      signs.

PMID- 26224249
TI  - Translational research in ARDS patients: new biological phenotypes.

PMID- 26224250
TI  - Cafe Variome: general-purpose software for making genotype-phenotype data
      discoverable in restricted or open access contexts.
AB  - Biomedical data sharing is desirable, but problematic. Data "discovery"
      approaches-which establish the existence rather than the substance of data
      precisely connect data owners with data seekers, and thereby promote data
      sharing. Cafe Variome (http://www.cafevariome.org) was therefore designed to
      provide a general-purpose, Web-based, data discovery tool that can be quickly
      installed by any genotype-phenotype data owner, or network of data owners, to
      make safe or sensitive content appropriately discoverable. Data fields or content
      of any type can be accommodated, from simple ID and label fields through to
      extensive genotype and phenotype details based on ontologies. The system provides
      a "shop window" in front of data, with main interfaces being a simple search box
      and a powerful "query-builder" that enable very elaborate queries to be
      formulated. After a successful search, counts of records are reported grouped by
      "openAccess" (data may be directly accessed), "linkedAccess" (a source link is
      provided), and "restrictedAccess" (facilitated data requests and subsequent
      provision of approved records). An administrator interface provides a wide range
      of options for system configuration, enabling highly customized single-site or
      federated networks to be established. Current uses include rare disease data
      discovery, patient matchmaking, and a Beacon Web service. 

PMID- 26224251
TI  - Trials and tribulations of conducting interventional studies in urban slums of a
      developing country: Experiences from Kolkata, India.
AB  - Experimental studies involving human subjects provide most internally valid
      evidences in epidemiological research due to their robust methodology. While
      conducting population-based interventional studies, to achieve external validity,
      inclusion of information from vulnerable groups like urban slum-dwellers of the
      developing world, in the epidemiological estimates is of paramount importance.
      The challenges faced while conducting 2 consecutive large-scale, community-based
      vaccine trials in urban slums of Kolkata, India are presented in this article.
      Interventions in these communities often get constrained by issues pertaining to
      human rights and benefits, socio-cultural factors, political environment,
      methodological shortcomings in addition to the challenges in ensuring community
      participation. While conducting these trials although we intermittently faced
      obstacles, by virtue of having a long term and robust surveillance system and
      developing a trusted relationship between the researchers, community leaders and
      residents we were able to come up with a commendable community participation
      which culminated into the success of the interventions. Bridging the gap between
      research and field operations by incorporating knowledge gathered from
      interventional studies and making strategies to improve health conditions of
      these informal settlers is a major unfulfilled agenda. We believe the lessons
      learnt during our research will help researchers while developing efficient
      interventions in similar setting. 

PMID- 26224252
TI  - Weber-Christian disease presenting with lung nodules dramatically improved with
      corticosteroid therapy: one case report and literature review.
AB  - Weber-Christian disease (WCD) is a chronic recurrent organ disease characterized
      by the formation of painful dense nodes in subcutaneous fat tissues, free from
      suppuration and accompanied by episodic temperature changes, chills and muscular
      pain. Sometimes it can involve the visceral organs. WCD often relapses during
      irregular intervals. It is a rare autoimmune inflammatory disorder of
      subcutaneous adipose tissue. However, lung involvement in WCD is rare. Here we
      report a man presenting with lung nodules. He was diagnosed as having WCD and
      successfully treated by corticosteroid and immonosuppressive agents. A 53-year
      old male presented with a 2.5-year history of painful subcutaneous nodules on his
      trunk and limbs, accompanied by fever, night sweats, fatigue and malaise. A skin
      biopsy showed fat degeneration with foamy cells and infiltration of mononuclear
      cells. He was diagnosed as panniculitis and effectively treated by corticosteroid
      therapy at first. However, symptoms relapsed when the dosage of corticosteroid
      was tapered, and multiple lung nodules were found with the symptom of dyspnea in
      chest computed tomography scan during the follow-up period. Histological
      examination of the biopsy specimens from the lung was compatible with
      panniculitis change in the subcutanous nodule. Combination therapy of
      corticosteroid with cyclophosphamide was effective during the following 27
      months.

PMID- 26224253
TI  - Efficacy of Multilayered Hepatocyte Sheet Transplantation for Radiation-Induced
      Liver Damage and Partial Hepatectomy in a Rat Model.
AB  - Although cell sheet technology has recently been developed for use in both animal
      experiments and in the clinical setting, it remains unclear whether transplanted
      hepatocyte sheets improve the liver function in vivo. Radiation-induced liver
      damage (RILD) combined with partial hepatectomy (PH) has been reported to
      suppress the proliferation of host hepatocytes and induce critical liver failure.
      The aim of this study was to improve the liver function in the above-mentioned
      diseased rat model (RILD + PH) using multilayered hepatocyte sheet
      transplantation. In this study, we used Fischer rats as a donor for primary
      hepatocytes and dermal fibroblast isolation. Cocultured multilayered hepatocyte
      sheets were generated by disseminating hepatocytes onto fibroblasts cultured
      beforehand on temperature-responsive culture dishes. Four cell sheets were
      transplanted into the recipient rats subcutaneously. Prior to transplantation,
      RILD (50 Gy) with 2/3PH was induced in the recipients. The same model was applied
      in the control group without transplantation. The serum was collected each week.
      The rats in both groups were sacrificed at 2 months after transplantation for the
      histological analysis. Consequently, the serum albumin concentrations were
      significantly higher in the transplant group than in the control group (54.3 +/-
      9.6 vs. 32.7 +/- 5.7 mg/ml; p < 0.01) after 2 months and comparable to the serum
      albumin levels in the normal rats (58.1 +/- 6.4 mg/ml). In addition, treatment
      with the transplanted sheets significantly improved the survival rate (57% vs.
      22%, p < 0.05), and the hepatocyte sheets showed the storage of albumin,
      glycogen, and bile canaliculus structures. Some hepatocytes and fibroblasts were
      positive for Ki-67, and vascularization was observed around the cell sheets.
      Transplanted multilayered hepatocyte sheets can survive with additional
      proliferative activity, thereby maintaining the liver function in vivo for at
      least 2 months, providing metabolic support for rats with RILD. 

PMID- 26224254
TI  - Graphene with outstanding anti-irradiation capacity as multialkylated
      cyclopentanes additive toward space application.
AB  - Multialkylated cyclopentanes (MACs), a class of synthetic hydrocarbon fluid have
      attracted intensive interest as possible space lubricants due to a series of
      unique physical and chemical properties. Here, we used graphene with high
      mechanical strength and chemical inertness as lubricant additive to explore its
      potential for space application. The effects of space irradiation on graphene and
      the tribological properties of graphene as lubricant additive were firstly
      investigated in detail under simulated space environment composed of high vacuum,
      high/low temperature and irradiation. Results demonstrate that graphene not only
      possesses outstanding anti-irradiation capacity but also significantly improves
      the space performance and tribological properties of MACs, which depends on the
      excellent physicochemical properties and high load-carrying ability of graphene
      as well as more effective separation of the sliding surfaces. 

PMID- 26224255
TI  - Freshwater ice as habitat: partitioning of phytoplankton and bacteria between ice
      and water in central European reservoirs.
AB  - Abundant phytoplankton and bacteria were identified by high-throughput 16S rRNA
      tag Illumina sequencing of samples from water and ice phases collected during
      winter at commercial fish ponds and a sand pit lake within the UNESCO Trebon
      Basin Biosphere Reserve, Czech Republic. Bacterial reads were dominated by
      Proteobacteria and Bacteroidetes. Despite dominance by members of just two phyla,
      UniFrac principal coordinates analysis of the bacterial community separated the
      water community of Klec fish pond, as well as the ice-associated community of
      Klec-Sand Pit from other samples. Both phytoplankton and cyanobacteria were
      represented with hundreds of sequence reads per sample, a finding corroborated by
      microscopy. In particular, ice from Klec-Sand Pit contained high contributions
      from photoautotrophs accounting for 25% of total reads with reads dominated by
      single operational taxonomic units (OTUs) of the cyanobacterium Planktothrix sp.
      and two filamentous diatoms. Dominant OTUs recovered from ice were largely absent
      (< 0.01%) from underlying water suggestive of low floristic similarity of
      phytoplankton partitioned between these phases. Photosynthetic characterization
      of phototrophs resident in water and ice analysed by variable chlorophyll a
      fluorescence showed that communities from both phases were photosynthetically
      active, thus supporting ice as viable habitat for phytoplankton in freshwater
      lakes and reservoirs. 

PMID- 26224256
TI  - Tuning the stereoselectivity of a DNA-catalyzed michael addition through covalent
      modification.
AB  - Complexes of G-quadruplex DNA and Cu(II) ions have previously been applied as
      catalysts in asymmetric reactions, but the largely unspecific and noncovalent
      nature of the interaction has impeded understanding of the structural basis of
      catalysis. To better control the formation of a catalytically competent species,
      DNA quadruplexes were derivatized with linker-bpy-Cu(II) complexes in a site
      specific manner and applied in asymmetric aqueous Michael additions. These
      modified quadruplexes exhibited high rate acceleration and stereoselectivity.
      Different factors were found to be important for the catalytic performance of the
      modified G-quadruplexes, among them, the position of modification, the topology
      of the quadruplex, the nature of the ligand, and the length of the linker between
      the ligand and DNA. Moving the same ligand by just two nucleotides inverted the
      stereochemical outcome: quadruplexes modified at position 10 formed the (-)
      enantiomer with up to 92 % ee, while DNA derivatized at position 12 formed the
      (+)-enantiomer with up to 75 % ee. This stereopreference was maintained when
      applied to structurally different Michael acceptors. This work demonstrates a new
      and simple way to tune the stereoselectivity in DNA-based asymmetric catalysis. 

PMID- 26224257
TI  - A Model-based approach for microvasculature structure distortion correction in
      two-photon fluorescence microscopy images.
AB  - This paper investigates a postprocessing approach to correct spatial distortion
      in two-photon fluorescence microscopy images for vascular network reconstruction.
      It is aimed at in vivo imaging of large field-of-view, deep-tissue studies of
      vascular structures. Based on simple geometric modelling of the object-of
      interest, a distortion function is directly estimated from the image volume by
      deconvolution analysis. Such distortion function is then applied to subvolumes of
      the image stack to adaptively adjust for spatially varying distortion and reduce
      the image blurring through blind deconvolution. The proposed technique was first
      evaluated in phantom imaging of fluorescent microspheres that are comparable in
      size to the underlying capillary vascular structures. The effectiveness of
      restoring three-dimensional (3D) spherical geometry of the microspheres using the
      estimated distortion function was compared with empirically measured point-spread
      function. Next, the proposed approach was applied to in vivo vascular imaging of
      mouse skeletal muscle to reduce the image distortion of the capillary structures.
      We show that the proposed method effectively improve the image quality and reduce
      spatially varying distortion that occurs in large field-of-view deep-tissue
      vascular dataset. The proposed method will help in qualitative interpretation and
      quantitative analysis of vascular structures from fluorescence microscopy images.

PMID- 26224259
TI  - Route memory in an unfamiliar homogeneous environment: a comparison of two
      strategies.
AB  - Humans use many strategies for navigation. Strategies utilizing cognitive
      salience of landmark have not been tested for application. In this study, we
      compared two strategies that humans use while navigating in an unfamiliar
      homogenous environment to remember the route. First strategy, called route
      learning, involved remembering sequence of turns, while second strategy used a
      commonly known memory technique method of loci with slight modification. In route
      learning, participants did not rely on any landmark (no-landmark condition),
      while in method of loci they visualized personally significant landmarks
      (imagined condition). Two videos, each having nine identical turns (3 rights, 3
      lefts and 3 straights) with no distinguishing feature at any turn, were developed
      using Trimble Sketchup and shown to 32 participants. The experiment was conducted
      in three phases. In the first phase, participants generated a list of personally
      known items to be used as landmarks. In the second phase, they saw the first
      video and were required to remember the sequence of turns. In the second video,
      they were required to imagine a landmark from the list generated in the first
      phase at each turn and associate the turn with the imaginary landmark. In both
      the tasks, the participants were asked to recall the sequence of turns as it
      appeared in the video. In the third phase, the participants were again asked to
      recall the sequence of turns. Result showed that memory of route was better
      without landmarks compared to imaginary landmark condition. This difference was
      insignificant when participants were tested again 20 min later. However, route
      memory was still better for no-landmark condition. The finding does not support
      earlier findings on route memory. Potential uses of method of loci for human
      wayfinding are mentioned.

PMID- 26224258
TI  - Single-case study in rehabilitation with SaM method (Sense and Mind): a proposal
      and analysis.
AB  - OBJECTIVE: The aim of the present case report is to describe a new rehabilitation
      approach for traumatic brain injury (TBI). BACKGROUND: TBI is a heterogeneous
      disorder that could be associated with cognitive and behavioral impairments. The
      clinical complexity of TBI patients requires a specialized and integrated
      approach that involves several rehabilitation experts (Mazzucchi in La
      riabilitazione neuropsicologica, Elsevier-Masson, Milan, 2012). SaM method (SaMM)
      (Risoli in La riabilitazione spaziale, Carocci Faber, Rome, 2013) is a new
      rehabilitation approach based on "embodied cognition" theory (Gallese and Lakoff
      in Cogn Neuropsychol 22(3):455-479, 2005) and has the aim to improve spatial
      abilities through structured body exercises. MATERIALS AND METHODS: The patient
      was a 35-year-old male who had TBI 9 months before. The patient was evaluated,
      before and after the treatment, with neuropsychological tests (Rey Test copy and
      reproduction, Elithorn Test, Trail Making Test, Rey Auditory Verbal Learning
      Test), Lawton Index for IADL, level of cognitive functioning, and a qualitative
      process-oriented assessment with SaMM exercises. The patient was treated with
      SaMM for 4 months, three times a week. RESULTS: Several of the executed
      assessments showed an improvement after SaMM treatment. The patient also reported
      amelioration in some daily activities such as swimming and using phone and money.
      DISCUSSION: Further investigations are necessary, but the SaMM appeared to be a
      useful complementary restitutive approach for TBI patients.

PMID- 26224260
TI  - Situated cognition and the phenomenology of place: lifeworld, environmental
      embodiment, and immersion-in-world.
AB  - This article makes use of a passage from novelist Gabriel Garcia Marquez's One
      Hundred Years of Solitude to illustrate Merleau-Ponty's phenomenology of the
      lived body and to consider what the related phenomenological concepts of place,
      environmental embodiment, and immersion-in-world might offer research in situated
      cognition. 

PMID- 26224261
TI  - Does pointing facilitate the recall of serial positions in visuospatial working
      memory?
AB  - The present study examined the question of whether pointing enhances the serial
      recall of visuospatial positions. Thirty-six participants were presented with 40
      target arrays varying in length from five to eight items, with each position
      appearing sequentially in red for 1 s. The task was to reproduce the order of
      presentation of the positions on a blank matrix. Results showed that, for five-,
      six-, and seven-item arrays, order memory was significantly better in the passive
      view than in the pointing condition, and the serial position curves displayed
      both recency and priority effects. Interestingly, the advantage of the passive
      view condition was more pronounced in the early than in the late positions. For
      eight-item arrays, no significant differences were found between the passive view
      and the pointing conditions. Overall, the present data provide no evidence in
      support of the view that pointing facilitates the recall of serial positions.

PMID- 26224262
TI  - Immersion as an embodied cognition shift: aesthetic experience and spatial
      situated cognition.
AB  - BACKGROUND: The main hypothesis of situated cognition is related to the origin of
      mental processes: the environment is thought to be the source of all cognitive
      processes. However, immersion enables a dual perception of space by enabling to
      perceive both the routine environment and a new way to see the world. AIMS: We
      want to provide a further insight into the transition from on-line cognition to
      off-line cognition: we want to show that aesthetic experience towards immersive
      art comes from the awareness that one's cognition depends on the environment.
      Although this specific cognition is not independent from the general environment,
      it abstracts the individuals from their idiosyncratic environment. Therefore,
      immersive art may induce cognitive processes that are borderline cases of
      situated cognition. METHOD: Aesthetic experience regarding spatial cognition will
      be described using an approach of embodied aesthetics, that is to say an approach
      which connects phenomenology of perception and cognitive sciences. RESULTS: No
      experiments are contemplated as of now. CONCLUSIONS: The experience of immersive
      art makes individuals become aware that their perceptual processes can adapt to
      the environment. Thus, the self-experience, which is typical of aesthetic
      experience, may be the cornerstone of off-line cognition.

PMID- 26224263
TI  - Perception of affordances during long-term exposure to weightlessness in the
      International Space station.
AB  - On Earth, visual eye height (VEH)--the distance from the observer's line of gaze
      to the ground in the visual scene--constitutes an effective cue in perceiving
      affordance such as the passability through apertures, based on the assumption
      that one's feet are on the ground. In the present study, we questioned whether an
      observer continues to use VEH to estimate the width of apertures during long-term
      exposure to weightlessness, where contact with the floor is not required. Ten
      astronauts were tested in preflight, inflight in the International Space Station,
      and postflight sessions. They were asked to adjust the opening of a virtual
      doorway displayed on a laptop device until it was perceived to be just wide
      enough to pass through (i.e., the critical aperture). We manipulated VEH by
      raising and lowering the level of the floor in the visual scene. We observed an
      effect of VEH manipulation on the critical aperture. When VEH decreased, the
      critical aperture decreased too, suggesting that widths relative to the body were
      perceived to be larger when VEH was smaller. There was no overall significant
      session effect, but the analysis of between-subjects variability revealed two
      participant profile groups. The effect of weightlessness was different for these
      two groups even though the VEH strategy remained operational during spaceflight.
      This study shows that the VEH strategy appears to be very robust and can be used,
      if necessary, in inappropriate circumstances such as free-floating, perhaps
      promoted by the nature of the visual scene.

PMID- 26224264
TI  - The "social" and "interpersonal" body in spatial cognition. The role of agency
      and interagency.
AB  - In order to interact effectively, we need to represent our action as produced by
      human beings. According to direct access theories, the first steps of visual
      information processing offer us an informed direct grasp of the situation,
      especially when social and interpersonal components are implicated. Biological
      system detection may be the gateway of such smart processes and then may
      influence initial stages of perception fostering adaptive social behaviour. To
      investigate early neural correlates of human agency detection in ecological
      situations with more high or low social impact, we compared scenes showing a
      human versus artificial agent interacting with a human agent. Twenty volunteers
      participated in the study. They were asked to observe dynamic visual stimuli
      showing realistic interactions. ERP (event-related potentials) were recorded.
      Each stimulus depicted an arm executing a gesture addressed to a human agent.
      Visual features of the arm were manipulated: in half of trials, it was real; in
      other trials, it was deprived of some details and transformed in a statue-like
      arm. EEG morphological analysis revealed an early negative deflection peaking at
      about 155 ms. Peak amplitude data have been statistically analysed by repeated
      measures ANOVAs. It was found that the peak was ampler in the left inferior
      posterior region when the gesturing arm was human. The early negative deflection,
      N150, which we found to be different between the human and artificial conditions,
      is presumably associated with human agency detection in high interpersonal
      context. 

PMID- 26224265
TI  - Automatic imitation of the arm kinematic profile in interacting partners.
AB  - Cognitive neuroscience, traditionally focused on individual brains, is just
      beginning to investigate social cognition through realistic interpersonal
      interaction. However, quantitative investigation of the dynamical sensorimotor
      communication among interacting individuals in goal-directed ecological tasks is
      particularly challenging. Here, we recorded upper-body motion capture of 23
      dyads, alternating their leader/follower role, in a tower-building task. Either a
      strategy of joining efforts or a strategy of independent action could in
      principle be used. We found that arm reach velocity profiles of participants
      tended to converge across trials. Automatic imitation of low-level motor control
      parameters demonstrates that the task is achieved through continuous action
      coordination as opposed to independent action planning. Moreover, the leader
      produced more consistent and predictable velocity profiles, suggesting an
      implicit strategy of signaling to the follower. This study serves as a validation
      of our joint goal-directed non-verbal task for future applications. In fact, the
      quantification of human-to-human continuous sensorimotor interaction, in a way
      that can be predicted and controlled, is probably one of the greatest challenges
      for the future of human-robot interaction. 

PMID- 26224266
TI  - Planning grasps for object manipulation: integrating internal preferences and
      external constraints.
AB  - Grasp selection for object manipulation depend on a person's preferences (e.g.,
      comfortable grasp) and the object's shape (i.e., how the object can be grasped).
      Both have to be matched when planning to grasp an object. According to the
      simulation hypothesis, humans simulate the action outcome for each of the grasp
      options to select the best grasp. However, if an object offers many different
      grasp options, further processing is necessary to reduce the number of
      possibilities. According to the preference hypothesis, a preferred grasp is first
      computed and then adjusted to comply with the objects' shape, if necessary. To
      test the hypotheses, we asked participants to grasp knobs that could be grasped
      with two, four, or an unconstrained range of grasps. When participants chose
      among two or four options, planning time increased with the number of possible
      grasps which is in line with the simulation hypothesis. However, when grasps were
      unconstrained, planning times were as short as in the two-grasp condition,
      suggesting another--possibly preference-based--selection process in this case. In
      contrast to planning time, grasp choices were comparable regardless of the knob's
      shape. This suggests a common criterion most likely determined grasp selection in
      all conditions.

PMID- 26224267
TI  - Long-lasting reduction in postural asymmetry by prism adaptation after right
      brain lesion without neglect.
AB  - BACKGROUND: Right brain damage (RBD) involves postural asymmetry and spatial
      frame disorders. In acute RBD patients, postural asymmetry is immediately reduced
      after one single session of prism adaptation (PA), without assessment of effects
      on spatial frames. AIM: To assess long-term effects of PA on posture and spatial
      frames in chronic RBD patients, without neglect. METHOD: Six chronic RBD patients
      without neglect (mean delay 45 months) were included. Each patient sustained 10
      PA sessions of 20 min during 2 weeks. Outcome measures were: (1) posturographic
      analysis (mediolateral position of centre of pressure (X cop), (2) subjective
      straight ahead (SSA) and perception of longitudinal body axis (LBA). Each
      parameter was assessed by three pretests and three post-tests (+2 h, day + 3 and
      day + 7). RESULTS: In pretests, patients showed a shift of the X cop and SSA. In
      post-tests, results displayed (1) a significant reduction in mediolateral
      postural asymmetry at D + 7; (2) a significant left deviation of SSA at D + 3 and
      enduring at D + 7; and (3) no significant modification of LBA. The mean curves of
      X cop and SSA between pre- and post-tests were similar. CONCLUSIONS: PA involves
      persistent reduction in postural asymmetry in RBD patients without neglect. These
      findings were obtained at a chronic stage. This new effect cannot be explained by
      reduction in spatial attentional shift. Improvement may be explained by a better
      calibration of extra personal space frames used for posture, without effect on
      personal space frame. Findings argue in favour of a bottom-up effect of PA on
      mechanisms underlying spatial cognition.

PMID- 26224268
TI  - Formation of spatial thinking skills through different training methods.
AB  - Spatial training can be durable and transferable if the training involves
      cognitive process-based tasks. The current study explored different spatial
      training methods and investigated the sequences of process-based mental
      simulation that was facilitated by various structures of external spatial
      representation, 3D technology, spatial cues, and/or technical languages. A total
      of 115 Columbia University's students were conducted through three experiments
      using a between-subjects design to examine the effects of spatial training
      methods on spatial ability performance. The conditions for training environments
      included 3D-virtual and 3D-physical interactions with abstract (nonsense
      geometric) and concrete (everyday-object) contents. Overall, learners in the
      treatment conditions improved in their spatial skills significantly more than
      those in the control conditions. Particularly, 3D-direct-manipulation conditions
      in the third experiment added promising results about the specific sequences
      during spatial thinking formation processes. 

PMID- 26224269
TI  - Socio-Spatial Intelligence: social media and spatial cognition for territorial
      behavioral analysis.
AB  - Investigative analysts gather data from different sources, especially from social
      media (SM), in order to shed light on cognitive factors that may explain criminal
      spatial behavior. A former research shows how tweets can be used to estimate
      private points of interest. Authors' aim was to demonstrate, as they extend the
      analysis to a wider statistical base, how social maps and Web applications could
      be used in investigative analysis and spatial cognition research. A total of 100
      Twitter accounts with approximately 250 tweets each were submitted to common
      geographical techniques (measures such as Convex-Hull, Mean-Center, Median
      Center, Standard-Deviation-Ellipse) in order to test the hypothesis that user
      areas of activity are predictable. Predictions were tested through a set of
      specific information: clear reference to areas of activity and clear reference
      about user's residence. Simple algorithms and procedures demonstrated that they
      could be used to predict where SM users live, giving positive results in about
      4/5 cases and giving indications about their home location. In fact, all home
      positions were found in the Convex-Hull and most of them in the Standard
      Deviation-Ellipse. Furthermore, in up to 80% of cases, houses were found within a
      buffer zone of 1.500 m with Median-Center as centrum (70% using Median-Center as
      centrum) with a minimum effectiveness threshold of 12-13 tweets. SM may help in
      studying people mobility and their cognition of space and, moreover, where they
      live, or their traveling behavior. The processing of geographical data in
      conjunction with the SM analysis may facilitate the construction of models
      describing specific behavior of people. The use of geographical information
      system tools and SM analysis represents an effective approach in order to acquire
      spatial and territorial information, referred to social relationship. The results
      may be used successfully in the understanding of social dynamics and for the
      prevention of criminal behavior.

PMID- 26224270
TI  - Neuromodelling based on evolutionary robotics: on the importance of motor control
      for spatial attention.
AB  - Mainstream approaches to modelling cognitive processes have typically focused on
      (1) reproducing their neural underpinning, without regard to sensory-motor
      systems and (2) producing a single, ideal computational model. Evolutionary
      robotics is an alternative possibility to bridge the gap between neural substrate
      and behavior by means of a sensory-motor apparatus, and a powerful tool to build
      a population of individuals rather than a single model. We trained 4 populations
      of neurorobots, equipped with a pan/tilt/zoom camera, and provided with different
      types of motor control in order to perform a cancellation task, often used to tap
      spatial cognition. Neurorobots' eye movements were controlled by (a) position,
      (b) velocity, (c) simulated muscles and (d) simulated muscles with fixed level of
      zoom. Neurorobots provided with muscle and velocity control showed better
      performances than those controlled in position. This is an interesting result
      since muscle control can be considered a particular type of position control.
      Finally, neurorobots provided with muscle control and zoom outperformed those
      without zooming ability. 

PMID- 26224271
TI  - Which numbers do you have in mind? Number generation is influenced by reading
      direction.
AB  - In Western participants, small numbers are associated with left and larger
      numbers with right space. A biological account proposes that brain asymmetries
      lead to these attentional asymmetries in number space. In contrast, a cultural
      account proposes that the direction of this association is shaped by reading
      direction. We explored whether number generation is influenced by reading
      direction in participants from a left-to-right (UK) and a right-to-left (Arab)
      reading culture. Participants generated numbers randomly while lying on their
      left and right side. The mean number generated by participants from a left-to
      right reading culture was smaller when they lay on their left than on their right
      side, and the opposite was found for participants from a right-to-left reading
      culture. Asymmetries in number space observed in number generation are more
      compatible with a cultural than biological account. 

PMID- 26224273
TI  - Decoupling, situated cognition and immersion in art.
AB  - Situated cognition seems incompatible with strong decoupling, where
      representations are deployed in the absence of their targets and are not oriented
      toward physical action. Yet, in art consumption, the epitome of a strongly
      decoupled cognitive process, the artwork is a physical part of the environment
      and partly controls the perception of its target by the audience, leading to
      immersion. Hence, art consumption combines strong decoupling with situated
      cognition. 

PMID- 26224272
TI  - Age-related differences in pointing accuracy in familiar and unfamiliar
      environments.
AB  - This study aimed to investigate age-related differences in spatial mental
      representations of familiar and unfamiliar places. Nineteen young adults (aged 18
      23) and 19 older adults (aged 60-74), all living in the same Italian town,
      completed a set of visuospatial measures and then pointed in the direction of
      familiar landmarks in their town and in the direction of landmarks in an unknown
      environment studied on a map. Results showed that older adults were less accurate
      in the visuospatial tasks and in pointing at landmarks in an unfamiliar
      environment, but performed as well as the young adults when pointing to familiar
      places. Pointing performance correlated with visuospatial tests accuracy in both
      familiar and unfamiliar environments, while only pointing in an unknown
      environment correlated with visuospatial working memory (VSWM). The spatial
      representation of well-known places seems to be well preserved in older adults
      (just as well as in young adults), while it declines for unfamiliar environments.
      Spatial abilities sustain the mental representations of both familiar and
      unfamiliar environments, while the support of VSWM resources is only needed for
      the latter. 

PMID- 26224274
TI  - Representations of body and space: theoretical concepts and controversies.
AB  - Recent years have seen a revived interest in how body and space are represented
      perceptually and how they affect human cognition and behaviour. Various
      conceptualisations of body and space have been proposed, alternately stressing
      neurophysiological, cognitive, or social aspects, but unified approaches are
      scarce. This short paper will give an overview of different views on body and
      space. At least three relevant dimensions can be identified in which concepts of
      body and space may differ: (1) perspective: while we conceptually differentiate
      between body and space perception, they imply each other and the underlying
      mechanisms overlap. (2) Level: representations of body and space may emerge at
      different processing levels, from spinal mechanisms guiding reflex movements to
      those we construct in our imagination. (3) Affect: representations of body and
      space are closely linked to affect, but this relationship has not received enough
      attention yet. Despite many empirical findings, our current views on body and
      space representations remain ambiguous. One problem may lie in the implicit
      diversity of "bodies" and "spaces" examined in different studies. Specifications
      of these concepts may help understand existing results better and are important
      for guiding future research. 

PMID- 26224276
TI  - Situational context is important: perceptual grouping modulates temporal
      perception.
AB  - Subjective time of an event in the sub-second range is often compressed or
      dilated by the situational context created by preceding and succeeding stimuli.
      How such context distorts psychological time is still an open question. Here, we
      pursued this issue by examining whether the perceptual grouping among successive
      visual stimuli modulates the perceived duration. Using a duration comparison
      task, we asked observers to judge the relative duration of a target and a
      comparison item, and estimated the apparent duration of the target from the
      corresponding psychometric function. The target was temporally flanked by a
      preceding item and a succeeding item. In different conditions, the target was
      more similar to either the preceding or the succeeding item. Results showed that
      perceptual grouping based on similarity modulated perceived duration.
      Specifically, when the target was grouped with the preceding item, its subjective
      duration was shorter than when it was grouped with the succeeding item.
      Interestingly, this pattern was observed when the preceding and target items were
      kept constant while the succeeding item was manipulated, suggesting that the
      effect depends, to some degree, on the holistic perceptual grouping rather than
      on fragmented processes. These results demonstrate that the situational context
      is an important factor in shaping temporal codes, thus bridging the seemingly
      independent perceptual feature processes and temporal representation. 

PMID- 26224275
TI  - Neurophysiological correlates of embodiment and motivational factors during the
      perception of virtual architectural environments.
AB  - The recent efforts aimed at providing neuroscientific explanations of how people
      perceive and experience architectural environments have largely justified the
      initial belief in the value of neuroscience for architecture. However, a
      systematic development of a coherent theoretical and experimental framework is
      missing. To investigate the neurophysiological reactions related to the
      appreciation of ambiances, we recorded the electroencephalographic (EEG) signals
      in an immersive virtual reality during the appreciation of interior designs. Such
      data have been analyzed according to the working hypothesis that appreciated
      environments involve embodied simulation mechanisms and circuits mediating
      approaching stimuli. EEG recordings of 12 healthy subjects have been performed
      during the perception of three-dimensional interiors that have been simulated in
      a CAVE system and judged according to dimensions of familiarity, novelty,
      comfort, pleasantness, arousal and presence. A correlation analysis on personal
      judgments returned that scores of novelty, pleasantness and comfort are
      positively correlated, while familiarity and novelty are in negative way.
      Statistical spectral maps reveal that pleasant, novel and comfortable interiors
      produce a de-synchronization of the mu rhythm over left sensorimotor areas.
      Interiors judged more pleasant and less familiar generate an activation of left
      frontal areas (theta and alpha bands), along an involvement of areas devoted to
      spatial navigation. An increase in comfort returns an enhancement of the theta
      frontal midline activity. Cerebral activations underlying appreciation of
      architecture could involve different mechanisms regulating corporeal, emotional
      and cognitive reactions. Therefore, it might be suggested that people's
      experience of architectural environments is intrinsically structured by the
      possibilities for action. 

PMID- 26224277
TI  - What's so difficult with adopting imagined perspectives?
AB  - Research on spatial cognition suggests that transformation processes and/or
      spatial conflicts may influence performance on mental perspective-taking tasks.
      However, conflicting findings have complicated our understanding about the
      processes involved in perspective-taking, particularly those giving rise to
      angular disparity effects, whereby performance worsens as the imagined
      perspective adopted deviates from one's actual perspective. Based on data from
      experiments involving mental perspective-taking in immediate and remote spatial
      layouts, we propose here a novel account for the difficulty with perspective
      taking. According to this account, the main difficulty lies in maintaining an
      imagined perspective in working memory, especially in the presence of salient
      sensorimotor information. 

PMID- 26224278
TI  - Transitive and intransitive gesture execution and observation compared to resting
      state: the hemodynamic measures (fNIRS).
AB  - The present study explored cortical correlates of gesture execution and
      observation in peripersonal space, using functional near-infrared spectroscopy
      (fNIRS). Moreover, a direct comparison was realized between resting state
      condition and execution/observation. Meaningful gestures produced in the presence
      (transitive action) or in the absence (intransitive action) of the object were
      considered in a real context (situated representation of gestures). Subjects were
      required to execute or observe transitive versus intransitive gestures during
      fNIRS registration. Gesture execution was related to higher brain activity
      (increased oxygenated hemoglobin levels) with respect to observation in motor
      areas (premotor cortex, PMC; supplementary motor cortex, SM1). In contrast, the
      posterior parietal cortex was similarly activated in case of both execution and
      observation task. Moreover, both tasks showed increased brain activity within
      these areas compared to resting state. Finally, it was shown that action
      execution and observation of transitive gestures was supported by similar
      parietal posterior areas. These findings support the hypothesis of a partial
      common network for observation and execution of gestures within peripersonal
      space, mainly in transitive condition. 

PMID- 26224279
TI  - Switching reference frame preferences during verbally assisted haptic graph
      comprehension.
AB  - Haptic-audio interfaces allow haptic exploration of statistical line graphs
      accompanied by sound or speech, thus providing access to exploration by visually
      impaired people. Verbally assisted haptic graph exploration can be seen as a task
      oriented collaborative activity between two partners, a haptic explorer and an
      observing assistant, who are disposed to individual preferences for using
      reference frames. The experimental findings reveal that haptic explorers' spatial
      reference frames are mostly induced by hand movements, leading to action
      perspective instead of conventionally left-to-right spatiotemporal perspective.
      Moreover, the communicational goal may result in a switch in perspective. 

PMID- 26224280
TI  - Promoting health wellness-The essentials of Chinese medicine.
AB  - Chinese medicine is a healing medicine which respect the power of human body
      itself. The essentials of Chinese medicine is promoting health wellness instead
      of disease management. Modern medicine just realized the limits of its theory. P4
      medicine (personalized, predictive, preventive, and participatory/precision)
      similar to Chinese medicine theory is beginning to representing the pioneer in
      the Western world. In this review, we summarized different domains of Chinese
      medicine. Based on the basic of promoting health wellness, we compared the
      fundamental theory of Chinese medicine to the new merging P4 medicine idea of
      Western medicine. We also discussed the potential for using modern computational
      medicine technique to integrate Chinese medicine theory and Western medicine
      theory. 

PMID- 26224281
TI  - Chinese medicine and integrative medicine in the United States.
AB  - Health wellness is a state of the homeostasis. Chinese medicine incorporate many
      concept including holistic medicine and individualized medicine to promote health
      wellness. Different domains of Chinese medicine were exclusively adopted after
      the first introduction of acupuncture to USA. Mayo as one of the best USA
      hospital created a foundation for the more widespread introduction of Chinese
      medicine into the US especially on the health wellness promotion. 

PMID- 26224282
TI  - The expression of calcitonin gene-related peptide on the neurons associated
      Zusanli (ST 36) in rats.
AB  - OBJECTIVE: To investigate the biochemical characteristic of the neurons
      associated Zusanli (ST 36) in the rat by using Alexa Fluor 594 conjugated cholera
      toxin subunit B (AF594-CTB) neural tracing and calcitonin gene-related peptide
      (CGRP) fluorescent immunohistochemical techniques. METHODS: Four male Sprague
      Dawley rats were injected with AF594-CTB into the corresponding area of the
      Zusanli in the human body. After 3 surviving days, the rat's spinal cord and
      dorsal root ganglia (DRGs) at lumbar segments were dissected following perfusion
      with 4% paraformaldehyde, cut into sections, and then stained with
      CGRPfluorescent immunohistochemical method. RESULTS: AF594-CTB labeled sensory
      neurons were detected in the L3-L6 DRGs with high concentration in L4 DRG, and
      the labeled motor neurons located in the dorsolateral and intermediate regions of
      lamina IX from L3-L5 segments with high concentration at L4. Meanwhile,
      CGRPpositive neural labeling distributed symmetrically on both sides of DRGs,
      anterior and dorsal horns of spinal cord. In the AF594-CTB labeled neurons, 37%
      sensory neurons and 100% motor neurons expressed CGRPpositive. CONCLUSION: These
      findings present the morphological evidence to demonstrate that the sensory and
      motor neurons associated Zusanli in the rat distributed with segmental and
      regional patterns, and contained CGRP-expression.

PMID- 26224284
TI  - Subjective Accounts of the Turning Points that Facilitate Desistance From
      Intimate Partner Violence.
AB  - The transition from persistence to desistance in male perpetrators of intimate
      partner violence (IPV) is an understudied phenomenon. This article examines the
      factors that initiate and facilitate primary desistance from IPV. The narratives
      of 22 male perpetrators of IPV (13 desisters and 9 persisters), 7 female
      survivors, and 9 programme (IPV interventions) facilitators, in England, were
      analysed using thematic analysis. In their accounts, the participants described
      how the change from persister to desister did not happen as a result of discrete
      unique incidents but instead occurred through a number of catalysts or stimuli of
      change. These triggers were experienced gradually and accumulated over time in
      number and in type. In particular, Negative consequences of violence and Negative
      emotional responses needed to accumulate so that the Point of resolve: Autonomous
      decision to change was finally realised. This process facilitated and initiated
      the path of change and thus primary desistance from IPV.

PMID- 26224283
TI  - A destructive feedback loop mediated by CXCL10 in central nervous system
      inflammatory disease.
AB  - OBJECTIVE: Paraneoplastic neurologic disorders (PND) are autoimmune diseases
      associated with cancer and ectopic expression of a neuronal antigen in a
      peripheral tumor. Patients with PND harbor high-titer antibodies and T cells in
      their serum and cerebrospinal fluid (CSF) that are specific to the tumor antigen,
      and treatment with the immunosuppressant FK506 (tacrolimus) decreases CSF white
      blood cell counts. The objective of this study was to determine the effect of
      FK506 on CSF chemokine levels in PND patients. METHODS: CSF samples before and
      after FK506 treatment were tested by multiplex assay for the presence of 27
      cytokines. Follow-up in vitro experiments aimed to determine whether T cells
      secrete CXCL10 in response to cognate antigen. RESULTS: Here we report that PND
      patients harbor high levels of the chemokine CXCL10 in their CSF. CXCL10 is a
      cytokine that recruits CXCR3(+) cells such as activated T cells, and we found
      that FK506 treatment specifically decreased CSF CXCL10 from among 27 cytokines
      tested. In vitro, CXCL10 was only produced during antigen-specific cognate
      interactions between T cells and antigen-presenting cells (APCs) when interferon
      gamma (IFNgamma) receptors were present on the T cell. INTERPRETATION: These
      results support a model in which antigen-specific T cell stimulation by PND APCs
      triggers IFNgamma, followed by CXCL10 production and further lymphocyte
      recruitment, suggesting that treatments targeting T cells or CXCL10 in the
      central nervous system (CNS) may interrupt a destructive positive feedback loop
      present in CNS inflammation.

PMID- 26224285
TI  - Abuse Experiences of Family Members, Child Maltreatment, and the Development of
      Sex Offending Among Incarcerated Adolescent Males.
AB  - Child sexual abuse is considered a risk factor for the development of sexual
      offending in adolescence. Beyond this, comparisons of the risk factor profiles
      between adolescent sex offenders (ASOs) and adolescent non-sex offenders (ANSOs)
      have uncovered minimal differences. However, differences between ASOs and ANSOs
      in terms of patterns in the abuse histories of their family members have rarely
      been studied. The aim in the current study was to retrospectively examine
      histories of abuse among family members of ASOs compared with ANSOs to determine
      whether and how these were related to youth abuse experiences and sexual
      offending in adolescence. The current study is based on a sample of 482
      incarcerated male adolescents (ASOs = 67, ANSOs = 415). Latent class analysis was
      conducted to determine multidimensional familial abuse profiles, and a series of
      logistic regression models were used to examine the relationship between family
      abuse profiles, youth abuse experiences, and adolescent sexual offending.
      Overall, familial abuse profiles were related to subsequent youth abuse
      experiences and sexual offending, and these abuse profiles differentiated ASOs
      and ANSOs.

PMID- 26224286
TI  - Support for Restorative Justice in a Sample of U.S. University Students.
AB  - Theories of restorative justice suggest that the practice works best when
      offenders are enmeshed in multiple interdependencies or attachments to others and
      belong to a culture that facilitates communitarianism instead of individualism.
      Restorative justice principles and practices are thus believed to be incongruent
      with the individualistic culture and legal system of the United States,
      especially compared with that of nations like Australia and Japan. Using a
      nonprobability convenience sample of students enrolled in a large public
      university in the United States, our study examines attitudes toward restorative
      justice as a fair and just process for reintegrating offenders and meeting the
      needs of victims. Results indicate that our sample holds less punitive attitudes
      than citizens in either Australia or Japan. Our findings are discussed in light
      of recent policy shifts in the United States that suggest a concerted move toward
      decarceration following the 2008 recession.

PMID- 26224287
TI  - Multiparametric MRI as an early biomarker of individual therapy effects during
      concomitant treatment of brain tumours.
AB  - The aim of this study was to determine the ability of multiparametric MRI to
      identify the early effects of individual treatment, during combined chemo
      radiotherapy on brain tumours. Eighty male rats bearing 9L gliosarcomas were
      randomized into four groups: untreated, anti-angiogenic therapy (SORA group),
      microbeam radiation therapy (MRT group) and both treatments (MRT+SORA group).
      Multiparametric MRI (tumour volume, diffusion-weighted MR imaging (ADC), blood
      volume fraction (BVf), microvessel index (VSI), vessel wall integrity (AUC(P846))
      and tissue oxygen saturation (StO2)) was performed 1 day before and 2, 5 and 8
      days after treatment initiation. Unpaired t-tests and one-way ANOVA were used for
      statistical analyses. Each MR parameter measured in our protocol was revealed to
      be sensitive to tumour changes induced by any of the therapies used (individually
      or combined). When compared with untreated tumours, SORA induced a decrease in
      BVf, VSI, StO2 and AUC(P846), MRT generated an increase in ADC and AUC(P846) and
      combined therapies yielded mixed effects: an increase in ADC and AUC(P846) and a
      decrease in BVf, StO2 and AUC(P846). MRT and MRT+SORA significantly slowed tumour
      growth. Despite these two groups presenting with similar tumour sizes, the
      information yielded from MR multiparameter assessment indicated that, when used
      concomitantly, each therapy induced distinguishable and appreciable physiological
      changes in the tumour. Our results suggest that multiparametric MRI can monitor
      the effects of individual treatments, used concomitantly, on brain tumours. Such
      monitoring would be useful for the detection of tumour resistance to
      drug/radiotherapy in patients undergoing concomitant therapies.

PMID- 26224288
TI  - Effect of Melatonin on Glutamate: BDNF Signaling in the Cerebral Cortex of
      Polychlorinated Biphenyls (PCBs)-Exposed Adult Male Rats.
AB  - Various epidemiological survey suggests that the central nervous system is the
      target for many environmental contaminants. One among them is Aroclor 1254, a
      mixture of polychlorinated biphenyls (PCBs) which explore a spectrum of
      biochemical and neurotoxic responses in humans and laboratory animals. Learning
      and motor coordination deficits are the profound effects of PCBs which may be
      related to cerebral dysfunction. The aim of the study is to elicit the protective
      effect of melatonin (Mel), a potent, blood brain permeable antioxidant against
      the effect of Aroclor 1254 on the signaling of glutamate-principal excitatory
      neurotransmitter and brain derived neurotrophic factor (BDNF) in the cerebral
      cortex of adult rats which plays a key role in brain functions. Adult male Wistar
      rats were grouped into four and treated intraperitonealy (i.p) Group I with corn
      oil (Control), Group II with PCBs (2 mg/kg/bwt), Group III with PCBs + Mel (2
      mg/kg/bwt + 5 mg/kg/bwt) and Group IV with Mel (5 mg/kg/bwt). The protein
      expression of glutamate signaling molecules and mRNA expressions of GLAST, BDNF
      signaling molecules were analyzed. The results suggest that simultaneous
      melatonin treatment significantly attenuated the NMDA receptor mediated glutamate
      excitotoxicity and protects the inhibition of BDNF signaling caused by PCBs
      exposure in cerebral cortex of adult male rats. Schematic pathway illustrating
      the proposed mechanism by which melatonin protects against A1254 mediated
      glutamate induced neurodegeneration in the cerebral cortex of adult male rats.
      PCBs induced neurodegeneration is caused by the overactivation of NMDAR, followed
      by the activation of voltage dependent calcium channels leading to the increase
      in intracellular Ca(2+) that stimulates calpain. Calpain inturn inhibits the PKA
      alpha and neurtrophin BDNF, its receptor and downstream signaling MAPK pathway
      leading to neurodegeneration. Melatonin had scavenged the ROS produced by PCBS
      and decreased the NMDAR expression which inturn protected the cells from
      neurodegeneration. 

PMID- 26224290
TI  - CORR Insights: The Minimum Clinically Important Difference of the Patient-rated
      Wrist Evaluation Score for Patients With Distal Radius Fractures.

PMID- 26224289
TI  - Biochemical, Metabolic, and Behavioral Characteristics of Immature Chronic
      Hyperphenylalanemic Rats.
AB  - Phenylketonuria and hyperphenylalanemia are inborn errors in metabolism of
      phenylalanine arising from defects in steps to convert phenylalanine to tyrosine.
      Phe accumulation causes severe mental retardation that can be prevented by timely
      identification of affected individuals and their placement on a Phe-restricted
      diet. In spite of many studies in patients and animal models, the basis for
      acquisition of mental retardation during the critical period of brain development
      is not adequately understood. All animal models for human disease have advantages
      and limitations, and characteristics common to different models are most likely
      to correspond to the disorder. This study established similar levels of Phe
      exposure in developing rats between 3 and 16 days of age using three models to
      produce chronic hyperphenylalanemia, and identified changes in brain amino acid
      levels common to all models that persist for ~16 h of each day. In a
      representative model, local rates of glucose utilization (CMRglc) were determined
      at 25-27 days of age, and only selective changes that appeared to depend on Phe
      exposure were observed. CMRglc was reduced in frontal cortex and thalamus and
      increased in hippocampus and globus pallidus. Behavioral testing to evaluate
      neuromuscular competence revealed poor performance in chronically
      hyperphenylalanemic rats that persisted for at least 3 weeks after cessation of
      Phe injections and did not occur with mild or acute hyperphenylalanemia. Thus,
      the abnormal amino acid environment, including hyperglycinemia, in developing rat
      brain is associated with selective regional changes in glucose utilization and
      behavioral abnormalities that are not readily reversed after they are acquired.

PMID- 26224292
TI  - Erratum to: frequent femoral neck osteolysis with Birmingham mid-head resection
      resurfacing arthroplasty in young patients.

PMID- 26224291
TI  - Regional Intraosseous Administration of Prophylactic Antibiotics is More
      Effective Than Systemic Administration in a Mouse Model of TKA.
AB  - BACKGROUND: In human TKA studies, intraosseous regional administration (IORA) of
      prophylactic antibiotics achieves local tissue antibiotic concentrations 10 times
      greater than systemic administration. However, it is unclear if such high
      concentrations provide more effective prophylaxis. QUESTIONS/PURPOSES: We asked:
      (1) What prophylaxis dosage and route (intravenous [IV] versus IORA of
      prophylactic antibiotics) produce less in vivo bacterial burden compared with no
      antibiotic controls? (2) Compared with controls, what prophylaxis dosage and
      route yield fewer colony-forming units (CFUs) in euthanized animals in a model of
      TKA? (3) Is prophylactic IORA of antibiotics more effective than same-dose IV
      antibiotic administration in reducing CFUs? METHODS: Mice (six to nine per group)
      were block randomized to one of six prophylaxis regimens: control, systemic
      cefazolin (C100IV), IORA of cefazolin (C100IORA), systemic vancomycin (V110IV),
      low-dose systemic vancomycin (V25IV), and low-dose IORA of vancomycin (V25IORA).
      Surgery involved placement of an intraarticular knee prosthesis, followed by an
      inoculum of bioluminescent Staphylococcus aureus strain Xen36. Biophotonic
      imaging assessed in vivo bacterial loads, and after 4 days bacterial load was
      quantified using culture-based techniques. Comparisons were made for each
      prophylactic regimen to controls and between same-dose IV and IORA of
      prophylactic antibiotic regimens. RESULTS: Mice treated with systemic high-dose
      vancomycin, IORA of vancomycin, or IORA of cefazolin had lower in vivo
      Staphylococcus aureus burdens (median area under curve, Control: 5.0 * 10(6);
      V110IV: 1.5 * 10(6), difference of medians 3.5 * 10(6), p = 0.003; V25IV: 1.94 *
      10(6), difference 3.07 * 10(6), p = 0.49; V25IORA: 1.51 * 10(6), difference 3.5 *
      10(6), p = 0.0011; C100IORA: 1.55 * 10(6), difference 3.46 * 10(6), p = 0.0016;
      C100IV: 2.35 * 10(6), difference 2.66 * 10(6), p = 0.23.) Similar findings were
      seen with culture-based techniques on recovered implants. IORA of prophylactic
      antibiotics was more effective than same-dose IV administration in reducing
      bacterial load on recovered implants (median CFUs < 7.0 * 10(0) vs 2.83 * 10(2),
      p = 0.0183). CONCLUSIONS: IORA of prophylactic cefazolin and vancomycin was more
      effective than the same dose of antibiotic given systemically. The effectiveness
      of vancomycin in particular was enhanced by IORA of prophylactic antibiotics
      despite using a lower dose. CLINICAL RELEVANCE: Our study supports previous
      studies of IORA of prophylactic antibiotics in humans and suggests this novel
      form of administration has the potential to enhance the effectiveness of
      prophylaxis in TKA. Because of concerns regarding antibiotic stewardship, IORA of
      prophylactic vancomycin may be more appropriately restricted to patients having
      TKA who are at greater risk of infection, and clinical trials are in progress.

PMID- 26224293
TI  - Women demonstrate more pain and worse function before THA but comparable results
      12 months after surgery.
AB  - BACKGROUND: Many studies report differences in patient-reported outcome measures
      (PROMs) for men and women undergoing total hip arthroplasty (THA). Few studies
      have evaluated whether these are explained by corresponding differences in
      important preoperative factors. QUESTIONS/PURPOSES: (1) Are there differences
      between men and women in PROM scores preoperatively and 12 months after THA? (2)
      Do baseline differences in comorbidity, age, body mass index (BMI), and mental
      health status explain these differences in PROM scores? METHODS: Preoperatively,
      300 patients completed the Oxford Hip Score (OHS), WOMAC, and SF-12; 261 (86%) of
      them (129 women, 64 +/- 11 years; 132 men, 66 +/- 10 years) completed the same
      questionnaires 12 months postoperatively and also rated the acceptability of
      their current symptoms and change in general health. RESULTS: Preoperatively,
      women showed worse scores than men in the OHS (-1.9; 95% confidence interval, 
      3.6 to -0.3) and WOMAC (-6.3; -10.9 to -1.7). At 12 months postoperatively, the
      absolute scores for all PROMs were not significantly different. After controlling
      for BMI, age, comorbidity, SF-12 mental health scores, and sociodemographic
      characteristics, the baseline differences remained. CONCLUSIONS: Surgeons may be
      more reluctant to operate on women than men because they perceive that, because
      of their worse baseline status, women are likely to have worse outcomes; however,
      given that we found no evidence for differences in patient-reported outcomes at
      12 months, these suspicions would appear to be unfounded. Women and men can be
      expected to benefit to a similar extent from THA. LEVEL OF EVIDENCE: Level III,
      therapeutic study.

PMID- 26224294
TI  - A beta-mannanase from Paenibacillus sp.: Optimization of production and its
      possible prebiotic potential.
AB  - A thermotolerant bacterium Paenibacillus thiaminolyticus with an ability to
      produce extracellular beta-mannanase was isolated from a soil sample. Bacterium
      produced 45 U/mL beta-mannanase at 50  degrees C. The culture conditions for high
      level production of beta-mannanase were optimized. Optimized MS medium [wheat
      bran 2% (w/v), ammonium sulfate 0.3% (w/v), yeast extract, and peptone (0.025%
      each) pH 6.5] was inoculated with 2% of 16 H old culture.  The culture was
      incubated at 50  degrees C for 48 H resulting in 24-folds higher beta-mannanase
      production (1,100 +/- 50 U/mL). Optimum pH and temperature for enzyme activity of
      the crude enzyme was 6.0 and 60  degrees C, respectively. The enzyme demonstrated
      65% relative enzyme activity at 37  degrees C. The hydrolytic activity of the
      crude enzymatic preparation was assessed on various agro residues. Thin-layer
      chromatographic analysis showed that the enzyme activity to saccharify
      heteromannans resulted in production of a mixture of manno-oligosaccharides (MOS)
      and enzyme exhibited classic endo-activity. To evaluate the possible prebiotic
      potential of the MOS thus obtained, initial screening for their ability to
      support the growth of probiotics was carried out by the pure culture method.
      Bifidobacterium and Lactobacillus sp. responded positively to the addition of
      enzymatically derived oligosaccharides and their numbers increased significantly.

PMID- 26224295
TI  - Viscosity measurement based on the tapping-induced free vibration of sessile
      droplets using MEMS-based piezoresistive cantilevers.
AB  - We report a simple technique to measure the free vibration of microlitre-sized
      droplets using an array of thirteen MEMS-based piezoresistive cantilevers and
      demonstrate its application for the measurement of viscosity. Because the damping
      of the free vibration of a liquid droplet is known to be affected by the
      viscosity of the liquid, measuring the vibration of a droplet allows the
      viscosity to be estimated from a dilute sample volume. However, conventional
      methods to measure the droplet vibration require sophisticated apparatuses, which
      hinder the development of a portable viscometer. Here, we show that MEMS-based
      piezoresistive cantilevers can be an excellent tool to measure the vibration of a
      sessile droplet due to the high sensitivity and simplicity of the readout scheme.
      Using the cantilever array, we analyse the normal force distribution on the
      contact area of a sessile droplet in the static state and during the vibration.
      Next, we show that the viscosity (from ~1-30 mPa s) can be estimated within an
      error of less than 10% from the attenuation rate of the cantilever output during
      the tapping-induced vibration of small droplets (~2.4 MUL). In addition to the
      advantage of the small sample volume, the proposed viscometer has simple
      operation and readout schemes, which are desirable for many applications,
      including point-of-care testing and drug development. 

PMID- 26224296
TI  - Midupper arm circumference and weight-for-length z scores have different
      associations with body composition: evidence from a cohort of Ethiopian infants.
AB  - BACKGROUND: A midupper arm circumference (MUAC) <115 mm and weight-for-height z
      score (WHZ) or weight-for-length z score (WLZ) less than -3, all of which are
      recommended to identify severe wasting in children, often identify different
      children. The reasons behind this poor agreement are not well understood.
      OBJECTIVE: We investigated the association between these 2 anthropometric indexes
      and body composition to help understand why they identify different children as
      wasted. DESIGN: We analyzed weight, length, MUAC, fat-mass (FM), and fat-free
      mass (FFM) data from 2470 measurements from 595 healthy Ethiopian infants
      obtained at birth and at 1.5, 2.5, 3.5, 4.5, and 6 mo of age. We derived WLZs by
      using 2006 WHO growth standards. We derived length-adjusted FM and FFM values as
      unexplained residuals after regressing each FM and FFM against length. We used a
      correlation analysis to assess associations between length, FFM, and FM (adjusted
      and nonadjusted for length) and the MUAC and WLZ and a multivariable regression
      analysis to assess the independent variability of length and length-adjusted FM
      and FFM with either the MUAC or the WLZ as the outcome. RESULTS: At all ages,
      length showed consistently strong positive correlations with the MUAC but not
      with the WLZ. Adjustment for length reduced observed correlation coefficients of
      FM and FFM with the MUAC but increased those for the WLZ. At all ages, both
      length-adjusted FM and FFM showed an independent association with the WLZ and
      MUAC with higher regression coefficients for the WLZ. Conversely, length showed
      greater regression coefficients for the MUAC. At all ages, the MUAC was shown to
      be more influenced than was the WLZ by the FM variability relative to the FFM
      variability. CONCLUSIONS: The MUAC and WLZ have different associations with body
      composition, and length influences these associations differently. Our results
      suggest that the WLZ is a good marker of tissue masses independent of length. The
      MUAC acts more as a composite index of poor growth indexing jointly tissue masses
      and length. This trial was registered at www.controlled-trials.com as
      ISRCTN46718296.

PMID- 26224298
TI  - Lean-seafood intake reduces cardiovascular lipid risk factors in healthy
      subjects: results from a randomized controlled trial with a crossover design.
AB  - BACKGROUND: Observational studies have strongly indicated an association between
      fish consumption and reduced risk of cardiovascular disease, but data from
      randomized controlled trials have been inconclusive. OBJECTIVE: Our primary
      outcome in this study was to elucidate the potentials of the 2 main dietary
      protein sources lean seafood and nonseafood to modulate fasting and postprandial
      lipids in healthy subjects. We hypothesized that lean-seafood intake would reduce
      cardiovascular lipid risk factors in healthy subjects more than would the intake
      of nonseafood protein sources. DESIGN: This study was a randomized controlled
      trial with a crossover design. After 3-wk run-in periods and separated by a 5-wk
      washout period, 20 healthy subjects (7 men and 13 women) consumed 2 balanced
      diets that varied in main protein sources (60% of total dietary proteins from
      lean-seafood or nonseafood sources for 4 wk). At days 1 and 28 of each
      intervention, fasting and postprandial blood samples were collected before and
      after consumption, respectively, of test meals with cod or lean beef. RESULTS:
      Relative to the nonseafood intervention, the lean-seafood intervention reduced
      fasting (relative difference by diets: 0.31 mmol/L; P = 0.03) and postprandial (P
      = 0.01) serum triacylglycerol concentrations. The lower serum triacylglycerol
      concentration was associated with reduced fasting triacylglycerol in chylomicrons
      and very-low-density lipoproteins (VLDLs) (P = 0.004), reduced fasting VLDL
      particle size (P = 0.04), and a reduced postprandial concentration of medium
      sized VLDL particles (P = 0.02). The lean-seafood intervention prevented the
      elevated ratio of total cholesterol to HDL cholesterol in the fasted serum (P =
      0.03) and postprandial serum (P = 0.01) that was observed after the nonseafood
      intervention. CONCLUSION: The dietary protein source determines fasting and
      postprandial lipids in healthy individuals in a manner that may have an effect on
      the long-term development of cardiovascular disease. This study was registered at
      clinicaltrials.gov as NCT01708681.

PMID- 26224297
TI  - B-vitamin status and bone mineral density and risk of lumbar osteoporosis in
      older females in the United States.
AB  - BACKGROUND: Previous data suggest that elevated serum total homocysteine (tHcy)
      may be a risk factor for bone fracture and osteoporosis. Nutritional causes of
      elevated tHcy are suboptimal B-vitamin status. To our knowledge, this is the
      first nationally representative report on the relation of B vitamins and bone
      health from a population with folic acid fortification. OBJECTIVE: The purpose of
      this analysis was to examine the relation between B-vitamin status biomarkers and
      bone mineral density (BMD), risk of osteoporosis, and biomarkers of bone
      turnover. DESIGN: We examined the relation of tHcy, methylmalonic acid (MMA), and
      serum/red blood cell folate and total-body and lumbar spine BMD in women aged
      >=50 y participating in the NHANES 1999-2004 (n = 2806), a nationally
      representative cross-sectional survey. These are the only years with concurrent
      measurement of tHcy and whole-body dual-energy X-ray absorptiometry. We also
      examined B-vitamin biomarkers relative to bone turnover markers, bone alkaline
      phosphatase, and urinary N-terminal cross-linked telopeptide of type I collagen
      in a 1999-2002 subset with available data (n = 1813). RESULTS: In comparison with
      optimal concentrations, women with elevated tHcy were older with lower serum
      vitamin B-12, red blood cell folate, and dietary micronutrient intakes and had
      significantly higher mean +/- SE markers of bone turnover (bone alkaline
      phosphatase: 15.8 +/- 0.59 compared with 14.0 +/- 0.25 MUg/L; urinary N-terminal
      cross-linked telopeptide of type I collagen: 48.2 +/- 2.9 compared with 38.9 +/-
      0.90 nmol bone collagen equivalents per mmol creatinine/L). Elevated MMA (OR:
      1.88; 95% CI: 1.10, 3.18) and tHcy (OR: 2.17; 95% CI: 1.14, 4.15) were related to
      increased risk of lumbar osteoporosis. When examined as a continuous variable,
      tHcy was negatively associated, serum folates were positively associated, and MMA
      and vitamin B-12 were not significantly associated with lumbar and total-body
      BMD. CONCLUSION: In this nationally representative population of older US women
      with high exposure to B vitamins through food fortification and dietary
      supplements, only elevated tHcy and MMA were independently associated with risk
      of lumbar spine osteoporosis.

PMID- 26224299
TI  - Impact of an early-life intervention on the nutrition behaviors of 2-y-old
      children: a randomized controlled trial.
AB  - BACKGROUND: Despite an extensive well-child health service, 30% of New Zealand's
      2- to 4-y old children are overweight or obese. This suggests that additional
      intervention is necessary to establish healthy nutrition behaviors. OBJECTIVE:
      The aim of this study was to assess the effect of intervention from 0 to 18 mo of
      age on food and nutrient intake, eating behaviors, and parental feeding practices
      in 18- to 24-mo-old children. DESIGN: In total, 802 families with healthy infants
      were randomly allocated to 1 of 4 groups: Usual Care (UC); Food, Activity, and
      Breastfeeding (FAB); Sleep; or FAB and Sleep (Combination). All groups received
      standard "well-child" care. The FAB intervention comprised 7-8 additional
      contacts for education and support around breastfeeding, food, and activity. The
      Sleep intervention comprised 2 additional contacts for guidance about sleeping
      habits. Combination families received both interventions. A validated food
      frequency questionnaire assessed food intake at 2 y. A questionnaire assessed
      eating behaviors and parental feeding practices at 18 and 24 mo. RESULTS: At 2 y,
      there were no statistically significant differences in food and nutrient intake
      or eating behaviors in the groups receiving the FAB intervention (FAB,
      Combination; 325 children) compared with the groups who did not (Sleep, UC; 341
      children). With the use of a 5-point scale, small but statistically significant
      differences in parental feeding practices were observed in the groups receiving
      the FAB intervention: greater child control over eating (difference: 0.14; 95%
      CI: 0.02, 0.26) and less pressure to eat (difference: 0.18; 95% CI: 0.04, 0.32)
      at 18 mo, as well as greater encouragement of nutrient-dense foods at 24 mo
      (difference: 0.16; 95% CI: 0.03, 0.30). No statistically significant differences
      were observed between the groups who received the Sleep intervention (Sleep,
      Combination; 313 children) and those who did not, except higher meat intake in
      the former (11 g/d). CONCLUSION: Additional education and support for parents
      from birth did not improve nutrition behaviors in this population at 2 y of age.
      This trial was registered at clinicaltrials.gov as NCT00892983.

PMID- 26224301
TI  - Retraction of Tang G, Hu Y, Yin S-a, Wang Y, Dallal GE, Grusak MA, and Russell
      RM. beta-Carotene in Golden Rice is as good as beta-carotene in oil at providing
      vitamin A to children. Am J Clin Nutr 2012;96:658-64.

PMID- 26224300
TI  - Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a
      randomized trial.
AB  - BACKGROUND: Few well-controlled studies have comprehensively examined the effects
      of very-low-carbohydrate diets on type 2 diabetes (T2D). OBJECTIVE: We compared
      the effects of a very-low-carbohydrate, high-unsaturated fat, low-saturated fat
      (LC) diet with a high-carbohydrate, low-fat (HC) diet on glycemic control and
      cardiovascular disease risk factors in T2D after 52 wk. DESIGN: In this
      randomized controlled trial that was conducted in an outpatient research clinic,
      115 obese adults with T2D [mean +/- SD age: 58 +/- 7 y; body mass index (in
      kg/m(2)): 34.6 +/- 4.3; glycated hemoglobin (HbA1c): 7.3 +/- 1.1%; duration of
      diabetes: 8 +/- 6 y] were randomly assigned to consume either a hypocaloric LC
      diet [14% of energy as carbohydrate (carbohydrate <50 g/d), 28% of energy as
      protein, and 58% of energy as fat (<10% saturated fat)] or an energy-matched HC
      diet [53% of energy as carbohydrate, 17% of energy as protein, and 30% of energy
      as fat (<10% saturated fat)] combined with supervised aerobic and resistance
      exercise (60 min; 3 d/wk). Outcomes were glycemic control assessed with use of
      measurements of HbA1c, fasting blood glucose, glycemic variability assessed with
      use of 48-h continuous glucose monitoring, diabetes medication, weight, blood
      pressure, and lipids assessed at baseline, 24, and 52 wk. RESULTS: Both groups
      achieved similar completion rates (LC diet: 71%; HC diet: 65%) and mean (95% CI)
      reductions in weight [LC diet: -9.8 kg (-11.7, -7.9 kg); HC diet: -10.1 kg (
      12.0, -8.2 kg)], blood pressure [LC diet: -7.1 (-10.6, -3.7)/-6.2 (-8.2, -4.1) mm
      Hg; HC diet: -5.8 (-9.4, -2.2)/-6.4 (-8.4, -4.3) mm Hg], HbA1c [LC diet: -1.0% (
      1.2%, -0.7%); HC diet: -1.0% (-1.3%, -0.8%)], fasting glucose [LC diet: -0.7
      mmol/L (-1.3, -0.1 mmol/L); HC diet: -1.5 mmol/L (-2.1, -0.8 mmol/L)], and LDL
      cholesterol [LC diet: -0.1 mmol/L (-0.3, 0.1 mmol/L); HC diet: -0.2 mmol/L (-0.4,
      0.03 mmol/L)] (P-diet effect >= 0.10). Compared with the HC-diet group, the LC
      diet group achieved greater mean (95% CI) reductions in the diabetes medication
      score [LC diet: -0.5 arbitrary units (-0.7, -0.4 arbitrary units); HC diet: -0.2
      arbitrary units (-0.4, -0.06 arbitrary units); P = 0.02], glycemic variability
      assessed by measuring the continuous overall net glycemic action-1 [LC diet: -0.5
      mmol/L (-0.6, -0.3 mmol/L); HC diet: -0.05 mmol/L (-0.2, -0.1 mmol/L); P =
      0.003], and triglycerides [LC diet: -0.4 mmol/L (-0.5, -0.2 mmol/L); HC diet: 
      0.01 mmol/L (-0.2, 0.2 mmol/L); P = 0.001] and greater mean (95% CI) increases in
      HDL cholesterol [LC diet: 0.1 mmol/L (0.1, 0.2 mmol/L); HC diet: 0.06 mmol/L (
      0.01, 0.1 mmol/L); P = 0.002]. CONCLUSIONS: Both diets achieved substantial
      weight loss and reduced HbA1c and fasting glucose. The LC diet, which was high in
      unsaturated fat and low in saturated fat, achieved greater improvements in the
      lipid profile, blood glucose stability, and reductions in diabetes medication
      requirements, suggesting an effective strategy for the optimization of T2D
      management. This trial was registered at www.anzctr.org.au as
      ACTRN12612000369820.

PMID- 26224302
TI  - Synthesis and physicochemical properties of novel lophine derivatives as
      chemiluminescent in vitro activators for detection of free radicals.
AB  - The overproduction of free radicals and reactive oxygen species (ROS) has been
      proved as a basic damage mechanism and cause for oxidative stress. Their
      measurement is often hindered by the low signal. This could be resolved with the
      application of luminescent probes (lophines, luminol, lucigenin, etc.). The focus
      of this study is to synthesize and describe the spectral properties and
      physicochemical characteristics of lophine and its derivatives as new
      chemiluminescent in vitro activators. The prepared luminophores are analogues of
      lophine. Their absorption maxima are in the range 329-340 nm, with good-to-high
      extinction coefficients. Their spectral properties are measured in methanol and
      buffer solutions with pH 3.5, 7.4 and 8.5. Same conditions were applied in the
      systems for chemiluminescent assay in vitro: (1) Fenton's (Fe(2+)+H2O2) for the
      generation of .OH and -OH species, (2) Hydrogen peroxide (H2O2), (3) Iron (II)
      sulfate (FeSO4), (4) Glutathione-peroxidase, monitoring the deactivation of H2O2,
      (5) Ascorbic acid-Fenton's reagent: Vit.C appears a strong oxidant, generating
      free-radical products when applied in higher than physiological concentrations,
      (6) Reduced alpha-nicotinamide adenine dinucleotide (NADH)-phenazine methosulfate
      for the generation of superoxide radicals (O2 (.-)). Lophine and all novel
      compounds do not alter the kinetics, except of the dimethyl amino substituted
      derivative (4-(3a,11b-dihydro-1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-N,N
      dimethylaniline) in the glutathione-peroxidase system, at pH 8.5. Same derivative
      showed a comparable or higher activity than Lucigenin and Rhodamine 6G. In
      neutral and acidic medium, in the Fenton's system, Rhodamine 6G was the most
      appropriate probe. In alkaline pH and oxidant H2O2, Lucigenin induced a signal
      twice as strong as the signal compared to all other activators.

PMID- 26224303
TI  - Fluorescence spectroscopic analysis of the structure and dynamics of Bacillus
      subtilis lipase A governing its activity profile under alkaline conditions.
AB  - Because of their vast diversity of substrate specificity and reaction conditions,
      lipases are versatile materials for biocatalysis. Lipase A from Bacillus subtilis
      (BSLA) is the smallest lipase yet discovered. It has the typical alpha/beta
      hydrolase fold but lacks a lid covering the substrate cleft. In this study, the
      pH-dependence of the activity, stability, structure, and dynamics of BSLA was
      investigated by fluorescence spectroscopy. By use of a fluorogenic substrate it
      was revealed that the optimum pH for BSLA activity is 8.5 whereas thermodynamic
      and kinetic stability are maximum at pH 10. The origin of this behavior was
      clarified by investigation of ANS (8-anilino-1-naphthalenesulfonic acid) binding
      and fluorescence quenching of the two single tryptophan mutants W31F and W42F.
      Variations in segmental dynamics were investigated by use of time-resolved
      fluorescence anisotropy. This analysis showed that the activity maximum is
      governed by high surface hydrophobicity and high segmental mobility of surface
      loops whereas the stability optimum is a result of low segmental mobility and
      surface hydrophobicity.

PMID- 26224305
TI  - Drug-induced hypereosinophilia related to tocilizumab therapy for rheumatoid
      arthritis.

PMID- 26224304
TI  - Citrus consumption and risk of basal cell carcinoma and squamous cell carcinoma
      of the skin.
AB  - Animal experiments have demonstrated the photocarcinogenic properties of
      furocoumarins, a group of naturally occurring chemicals that are rich in citrus
      products. We conducted a prospective study for citrus consumption and risk of
      basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on
      data from 41530 men in the Health Professionals Follow-up Study (1986-2010) and
      63759 women in the Nurses' Health Study (1984-2010) who were free of cancers at
      baseline. Over 24-26 years of follow-up, we documented 20840 incident BCCs and
      3544 incident SCCs. Compared to those who consumed citrus products less than
      twice per week, the pooled multivariable-adjusted hazard ratios were 1.03 [95%
      confidence interval (95% CI): 0.99-1.08] for BCC and 1.14 (95% CI: 1.00-1.30) for
      SCC for those who consumed two to four times per week, 1.06 (95% CI: 1.01-1.11)
      for BCC and 1.15 (95% CI: 1.02-1.28) for SCC for five to six times per week, 1.11
      (95% CI: 1.06-1.16) for BCC and 1.22 (95% CI: 1.08-1.37) for SCC for once to 1.4
      times per day and 1.16 (95% CI: 1.09-1.23) for BCC and 1.21 (95% Cl: 1.06-1.38)
      for SCC for 1.5 times per day or more (P trend = 0.001 for BCC and 0.04 for SCC).
      In contrast, consumption of non-citrus fruit and juice appeared to be inversely
      associated with risk of BCC and SCC. Our findings support positive associations
      between citrus consumption and risk of cutaneous BCC and SCC in two cohorts of
      men and women, and call for further investigations to better understand the
      potential photocarcinogenesis associated with dietary intakes. 

PMID- 26224306
TI  - Validity and measurement precision of the PROMIS physical function item bank and
      a content validity-driven 20-item short form in rheumatoid arthritis compared
      with traditional measures.
AB  - OBJECTIVE: To evaluate the content validity and measurement properties of the
      Patient-Reported Outcome Measurement Information System (PROMIS) physical
      function item bank and a 20-item short form in patients with RA in comparison
      with the HAQ disability index (HAQ-DI) and 36-item Short Form Health Survey (SF
      36) physical functioning scale (PF-10). METHODS: The content validity of the
      instruments was evaluated by linking their items to the International
      Classification of Functioning, Disability and Health (ICF) core set for RA. The
      measures were administered to 690 RA patients enrolled in the Dutch Rheumatoid
      Arthritis Monitoring registry. Measurement precision was evaluated using item
      response theory methods and construct validity was evaluated by correlating
      physical function scores with other clinical and patient-reported outcome
      measures. RESULTS: All 207 health concepts identified in the physical function
      measures referred to activities that are featured in the ICF. Twenty-three of 26
      ICF RA core set domains are featured in the full PROMIS physical function item
      bank compared with 13 and 8 for the HAQ-DI and PF-10, respectively. As
      hypothesized, all three physical function instruments were highly intercorrelated
      (r 0.74-0.84), moderately correlated with disease activity measures (r 0.44-0.63)
      and weakly correlated with age (rs 0.07-0.14). Item response theory-based
      analysis revealed that a 20-item PROMIS physical function short form covered a
      wider range of physical function levels than the HAQ-DI or PF-10. CONCLUSION: The
      PROMIS physical function item bank demonstrated excellent measurement properties
      in RA. A content-driven 20-item short form may be a useful tool for assessing
      physical function in RA.

PMID- 26224307
TI  - Predicting and preventing the development of rheumatoid arthritis.

PMID- 26224308
TI  - Src and cortactin promote lamellipodia protrusion and filopodia formation and
      stability in growth cones.
AB  - Src tyrosine kinases have been implicated in axonal growth and guidance; however,
      the underlying cellular mechanisms are not well understood. Specifically, it is
      unclear which aspects of actin organization and dynamics are regulated by Src in
      neuronal growth cones. Here, we investigated the function of Src2 and one of its
      substrates, cortactin, in lamellipodia and filopodia of Aplysia growth cones. We
      found that up-regulation of Src2 activation state or cortactin increased
      lamellipodial length, protrusion time, and actin network density, whereas down
      regulation had opposite effects. Furthermore, Src2 or cortactin up-regulation
      increased filopodial density, length, and protrusion time, whereas down
      regulation promoted lateral movements of filopodia. Fluorescent speckle
      microscopy revealed that rates of actin assembly and retrograde flow were not
      affected in either case. In summary, our results support a model in which Src and
      cortactin regulate growth cone motility by increasing actin network density and
      protrusion persistence of lamellipodia by controlling the state of actin-driven
      protrusion versus retraction. In addition, both proteins promote the formation
      and stability of actin bundles in filopodia. 

PMID- 26224309
TI  - Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in
      Schwann cell myelination.
AB  - During early development of the peripheral nervous system, Schwann cell
      precursors proliferate, migrate, and differentiate into premyelinating Schwann
      cells. After birth, Schwann cells envelop neuronal axons with myelin sheaths.
      Although some molecular mechanisms underlying myelination by Schwann cells have
      been identified, the whole picture remains unclear. Here we show that signaling
      through Tyro3 receptor tyrosine kinase and its binding partner, Fyn nonreceptor
      cytoplasmic tyrosine kinase, is involved in myelination by Schwann cells.
      Impaired formation of myelin segments is observed in Schwann cell neuronal
      cultures established from Tyro3-knockout mouse dorsal root ganglia (DRG). Indeed,
      Tyro3-knockout mice exhibit reduced myelin thickness. By affinity chromatography,
      Fyn was identified as the binding partner of the Tyro3 intracellular domain, and
      activity of Fyn is down-regulated in Tyro3-knockout mice, suggesting that Tyro3,
      acting through Fyn, regulates myelination. Ablating Fyn in mice results in
      reduced myelin thickness. Decreased myelin formation is observed in cultures
      established from Fyn-knockout mouse DRG. Furthermore, decreased kinase activity
      levels and altered expression of myelination-associated transcription factors are
      observed in these knockout mice. These results suggest the involvement of Tyro3
      receptor and its binding partner Fyn in Schwann cell myelination. This
      constitutes a newly recognized receptor-linked signaling mechanism that can
      control Schwann cell myelination. 

PMID- 26224310
TI  - The Myopic-Ubpy-Hrs nexus enables endosomal recycling of Frizzled.
AB  - Endosomal trafficking of signaling proteins plays an essential role in cellular
      homeostasis. The seven-pass transmembrane protein Frizzled (Fz) is a critical
      component of Wnt signaling. Although Wnt signaling is proposed to be regulated by
      endosomal trafficking of Fz, the molecular events that enable this regulation are
      not completely understood. Here we show that the endosomal protein Myopic (Mop)
      regulates Fz trafficking in the Drosophila wing disk by inhibiting the
      ubiquitination and degradation of Hrs. Deletion of Mop or Hrs results in
      endosomal accumulation of Fz and therefore reduced Wnt signaling. The in situ
      proximity ligation assay revealed a strong association between Mop and Hrs in the
      Drosophila wing disk. Overexpression of Hrs rescues the trafficking defect caused
      by mop knockdown. Mop aids in the maintenance of Ubpy, which deubiquitinates (and
      thus stabilizes) Hrs. In the absence of the ubiquitin ligase Cbl, Mop is
      dispensable. These findings support a previously unknown role for Mop in
      endosomal trafficking of Fz in Wnt-receiving cells. 

PMID- 26224311
TI  - Interlocked positive and negative feedback network motifs regulate beta-catenin
      activity in the adherens junction pathway.
AB  - The integrity of epithelial tissue architecture is maintained through adherens
      junctions that are created through extracellular homotypic protein-protein
      interactions between cadherin molecules. Cadherins also provide an intracellular
      scaffold for the formation of a multiprotein complex that contains signaling
      proteins, including beta-catenin. Environmental factors and controlled tissue
      reorganization disrupt adherens junctions by cleaving the extracellular binding
      domain and initiating a series of transcriptional events that aim to restore
      tissue homeostasis. However, it remains unclear how alterations in cell adhesion
      coordinate transcriptional events, including those mediated by beta-catenin in
      this pathway. Here were used quantitative single-cell and population-level in
      vitro assays to quantify the endogenous pathway dynamics after the proteolytic
      disruption of the adherens junctions. Using prior knowledge of isolated elements
      of the overall network, we interpreted these data using in silico model-based
      inference to identify the topology of the regulatory network. Collectively the
      data suggest that the regulatory network contains interlocked network motifs
      consisting of a positive feedback loop, which is used to restore the integrity of
      adherens junctions, and a negative feedback loop, which is used to limit beta
      catenin-induced gene expression. 

PMID- 26224312
TI  - CFAP54 is required for proper ciliary motility and assembly of the central pair
      apparatus in mice.
AB  - Motile cilia and flagella play critical roles in fluid clearance and cell
      motility, and dysfunction commonly results in the pediatric syndrome primary
      ciliary dyskinesia (PCD). CFAP221, also known as PCDP1, is required for ciliary
      and flagellar function in mice and Chlamydomonas reinhardtii, where it localizes
      to the C1d projection of the central microtubule apparatus and functions in a
      complex that regulates flagellar motility in a calcium-dependent manner. We
      demonstrate that the genes encoding the mouse homologues of the other C.
      reinhardtii C1d complex members are primarily expressed in motile ciliated
      tissues, suggesting a conserved function in mammalian motile cilia. The
      requirement for one of these C1d complex members, CFAP54, was identified in a
      mouse line with a gene-trapped allele. Homozygous mice have PCD characterized by
      hydrocephalus, male infertility, and mucus accumulation. The infertility results
      from defects in spermatogenesis. Motile cilia have a structural defect in the C1d
      projection, indicating that the C1d assembly mechanism requires CFAP54. This
      structural defect results in decreased ciliary beat frequency and perturbed cilia
      driven flow. This study identifies a critical role for CFAP54 in proper assembly
      and function of mammalian cilia and flagella and establishes the gene-trapped
      allele as a new model of PCD. 

PMID- 26224313
TI  - The cellular prion protein PrPc is a partner of the Wnt pathway in intestinal
      epithelial cells.
AB  - We reported previously that the cellular prion protein (PrP(c)) is a component of
      desmosomes and contributes to the intestinal barrier function. We demonstrated
      also the presence of PrP(c) in the nucleus of proliferating intestinal epithelial
      cells. Here we sought to decipher the function of this nuclear pool. In human
      intestinal cancer cells Caco-2/TC7 and SW480 and normal crypt-like HIEC-6 cells,
      PrP(c) interacts, in cytoplasm and nucleus, with gamma-catenin, one of its
      desmosomal partners, and with beta-catenin and TCF7L2, effectors of the canonical
      Wnt pathway. PrP(c) up-regulates the transcriptional activity of the beta
      catenin/TCF7L2 complex, whereas gamma-catenin down-regulates it. Silencing of
      PrP(c) results in the modulation of several Wnt target gene expressions in human
      cells, with different effects depending on their Wnt signaling status, and in
      mouse intestinal crypt cells in vivo. PrP(c) also interacts with the Hippo
      pathway effector YAP, suggesting that it may contribute to the regulation of gene
      transcription beyond the beta-catenin/TCF7L2 complex. Finally, we demonstrate
      that PrP(c) is required for proper formation of intestinal organoids, indicating
      that it contributes to proliferation and survival of intestinal progenitors. In
      conclusion, PrP(c) must be considered as a new modulator of the Wnt signaling
      pathway in proliferating intestinal epithelial cells. 

PMID- 26224315
TI  - Studying early stages of fibronectin fibrillogenesis in living cells by atomic
      force microscopy.
AB  - Fibronectin (FN) is an extracellular matrix protein that can be assembled by
      cells into large fibrillar networks, but the dynamics of FN remodeling and the
      transition through intermediate fibrillar stages are still incompletely
      understood. Here we have used a combination of fluorescence microscopy and time
      lapse atomic force microscopy (AFM) to visualize initial stages of FN
      fibrillogenesis in living fibroblasts at high resolution. Initial FN nanofibrils
      form within <5 min of cell-matrix contact and subsequently extend at a rate of
      0.25 MUm/min at sites of cell membrane retraction. FN nanofibrils display a
      complex linear array of globular features spaced at varying distances, indicating
      the coexistence of different conformational states within the fibril. In some
      cases initial fibrils extended in discrete increments of ~800 nm during a series
      of cyclical membrane retractions, indicating a stepwise fibrillar extension
      mechanism. In presence of Mn2+, a known activator of integrin adhesion to FN,
      fibrillogenesis was accelerated almost threefold to 0.68 MUm/min and fibrillar
      dimensions were increased, underlining the importance of integrin activation for
      early FN fibrillogenesis. FN fibrillogenesis visualized by time-lapse AFM thus
      provides new structural and mechanistic insight into initial steps of cell-driven
      FN fibrillogenesis.

PMID- 26224314
TI  - Inflammation-induced desmoglein-2 ectodomain shedding compromises the mucosal
      barrier.
AB  - Desmosomal cadherins mediate intercellular adhesion and control epithelial
      homeostasis. Recent studies show that proteinases play an important role in the
      pathobiology of cancer by targeting epithelial intercellular junction proteins
      such as cadherins. Here we describe the proinflammatory cytokine-induced
      activation of matrix metalloproteinase 9 and a disintegrin and metalloproteinase
      domain-containing protein 10, which promote the shedding of desmosomal cadherin
      desmoglein-2 (Dsg2) ectodomains in intestinal epithelial cells. Epithelial
      exposure to Dsg2 ectodomains compromises intercellular adhesion by promoting the
      relocalization of endogenous Dsg2 and E-cadherin from the plasma membrane while
      also promoting proliferation by activation of human epidermal growth factor
      receptor 2/3 signaling. Cadherin ectodomains were detected in the inflamed
      intestinal mucosa of mice with colitis and patients with ulcerative colitis.
      Taken together, our findings reveal a novel response pathway in which
      inflammation-induced modification of columnar epithelial cell cadherins decreases
      intercellular adhesion while enhancing cellular proliferation, which may serve as
      a compensatory mechanism to promote repair. 

PMID- 26224316
TI  - N-glycosylation controls the function of junctional adhesion molecule-A.
AB  - Junctional adhesion molecule-A (JAM-A) is an adherens and tight junction protein
      expressed by endothelial and epithelial cells. JAM-A serves many roles and
      contributes to barrier function and cell migration and motility, and it also acts
      as a ligand for the leukocyte receptor LFA-1. JAM-A is reported to contain N
      glycans, but the extent of this modification and its contribution to the
      protein's functions are unknown. We show that human JAM-A contains a single N
      glycan at N185 and that this residue is conserved across multiple mammalian
      species. A glycomutant lacking all N-glycans, N185Q, is able to reach the cell
      surface but exhibits decreased protein half-life compared with the wild- type
      protein. N-glycosylation of JAM-A is required for the protein's ability to
      reinforce barrier function and contributes to Rap1 activity. We further show that
      glycosylation of N185 is required for JAM-A-mediated reduction of cell migration.
      Finally, we show that N-glycosylation of JAM-A regulates leukocyte adhesion and
      LFA-1 binding. These findings identify N-glycosylation as critical for JAM-A's
      many functions. 

PMID- 26224318
TI  - Necrotizing pulmonary aspergillosis and ventricular assist device infection: case
      report and review of literature.
AB  - Necrotizing pulmonary aspergillosis and Aspergillus device infection are rare and
      have potentially fatal complications after left ventricular assist device (LVAD)
      implantation. To date, few cases of patients surviving Aspergillus device
      infection have been published, with survival reported only after device removal.
      We present a patient implanted with an LVAD in whom necrotizing pulmonary
      aspergillosis with device involvement was successfully treated by segmentectomy
      and prolonged antifungal treatment without device exchange or removal. Similar
      cases in the literature were searched for and are discussed in view of the
      severity of this complication. 

PMID- 26224319
TI  - Regio- and stereoselective synthesis of 2'-beta-substituted-fluoroneplanocin A
      analogues as potential anticancer agents.
AB  - A series of 2'-beta-substituted-6'-fluoro-cyclopentenyl-pyrimidines and -purines
      8 and 9 were successfully synthesized from d-ribose in a regio- and
      stereoselective manner. The functionalization at the C2-position of 6'-fluoro
      cyclopentenyl nucleosides was achieved via regioselective protection of a
      hydroxyl group at the C3-position and stereoselective formation of C2-triflate
      followed by direct SN2 reaction with a fluoro or azido nucleophile. All the
      synthesized compounds were evaluated for their anticancer activities in several
      tumor cell lines, but were found to be neither active nor toxic. 

PMID- 26224317
TI  - Tumor necrosis factor-related apoptosis-inducing ligand induces the expression of
      proinflammatory cytokines in macrophages and re-educates tumor-associated
      macrophages to an antitumor phenotype.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      candidate for cancer therapy, because it can induce apoptosis in various tumor
      cells but not in most normal cells. Although it is well known that TRAIL and its
      receptors are expressed in many types of normal cells, including immune cells,
      their immunological effects and regulatory mechanisms are still obscure. In the
      present study, we demonstrated that TRAIL affected the activity of NF-kappaB
      (nuclear factor-kappaB) and the expression of its downstream proinflammatory
      cytokines IL-1beta (interleukin-1beta), IL-6, and tumor necrosis factor alpha in
      macrophages. TRAIL also induced microRNA-146a (miR-146a) expression in an NF
      kappaB-dependent manner. As a result, miR-146a was involved as a negative
      feedback regulator in the down-regulation of proinflammatory cytokine expression.
      In addition, the suppression of histone deacetylase (HDAC) activities by
      trichostatin A improved miR-146a expression due to the up-regulation of the DNA
      binding activity of NF-kappaB at the miR-146a promoter in TRAIL-induced
      macrophages, suggesting that histone acetylation was involved in the suppression
      of miR-146a expression. Further investigation revealed that the HDAC subtype
      HDAC1 directly regulated the expression of miR-146a in TRAIL-stimulated
      macrophages. Finally, the TRAIL-sensitive human non small cell lung carcinoma
      cell line NCI-H460 was used to elucidate the physiological significance of TRAIL
      with respect to tumor-associated macrophages (TAMs). We demonstrated that TRAIL
      re-educated TAMs to an M1-like phenotype and induced cytotoxic effects in the
      tumor cells. These data provide new evidence for TRAIL in the immune regulation
      of macrophages and may shed light on TRAIL-based antitumor therapy in human
      patients. 

PMID- 26224320
TI  - Blood micronutrients and DNA damage in children.
AB  - SCOPE: Maintenance of normal cellular phenotype depends largely on accurate DNA
      replication and repair. DNA damage causes gene mutations and predisposes to
      cancer and other chronic diseases. Growing evidence indicates that nutritional
      factors are associated with DNA damage in adults; here, we investigate these
      associations in children. METHODS AND RESULTS: We conducted a cross-sectional
      study among 462 healthy children 3, 6, and 9 years of age. Blood was collected
      and micronutrient levels were measured. The cytokinesis-block micronucleus cytome
      assay was used to measure chromosomal DNA damage (micronuclei, nucleoplasmic
      bridges, and nuclear buds) in lymphocytes. Cell apoptosis, necrosis, and the
      nuclear division index were also measured. Nine loci in genes involved in folate
      metabolism and DNA repair were genotyped. Data were analyzed using linear
      regression with adjustment for potential confounders. Plasma calcium was
      positively associated with micronuclei and necrosis, and alpha-tocopherol
      negatively associated with apoptosis, nuclear division index, and nucleoplasmic
      bridges; lutein was positively associated with nucleoplasmic bridges. alpha
      tocopherol was positively associated with necrosis. CONCLUSION: DNA damage in
      healthy children may be influenced by blood micronutrient levels and certain
      genotypes. Further investigation of associations between nutritional status and
      genomic integrity in children is needed to shed additional light on potential
      mechanisms.

PMID- 26224321
TI  - Antibiotic resistance of Streptococcus pneumoniae colonising the nasopharynx of
      HIV-exposed Tanzanian infants.
AB  - OBJECTIVES: To determine antibiotic susceptibility of colonising pneumococcal
      serotypes in HIV-exposed infants before the introduction of the 13-valent
      pneumococcal conjugate vaccine (PCV13), because HIV-exposed infants are at
      increased risk of invasive pneumococcal infections. METHODS: Antibiotic
      susceptibility of 104 pneumococcal isolates, cultured from the nasopharynx from
      Tanzanian HIV-exposed infants, was determined using the disc diffusion method and
      the E-test according to EUCAST version 4.0 (2014) criteria. RESULTS: A total of
      69.2% of isolates were intermediately susceptible for benzyl penicillin (MIC 0.06
      2 mg/l ); no high-level resistance was found. All isolates but one were
      susceptible to ampicillin. Regarding non-beta-lactam antibiotics, 19.2% of
      isolates were resistant to doxycycline, 3.8% to erythromycin and 97.1% to
      trimethoprim/sulfamethoxazole. A total of 15.4% of isolates were resistant to
      three antibiotic classes or more. There were no differences in antibiotic
      susceptibility between vaccine and non-vaccine serotypes. Reduced susceptibility
      of colonising pneumococcal isolates for commonly used antibiotics is common in
      HIV-exposed Tanzanian infants. CONCLUSIONS: High-dose penicillin and ampicillin
      remain appropriate first choices for non-meningeal pneumococcal infections in
      this group.

PMID- 26224322
TI  - Nonsteroidal anti-inflammatory drugs for dysmenorrhoea.
AB  - BACKGROUND: Dysmenorrhoea is a common gynaecological problem consisting of
      painful cramps accompanying menstruation, which in the absence of any underlying
      abnormality is known as primary dysmenorrhoea. Research has shown that women with
      dysmenorrhoea have high levels of prostaglandins, hormones known to cause
      cramping abdominal pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs
      that act by blocking prostaglandin production. They inhibit the action of
      cyclooxygenase (COX), an enzyme responsible for the formation of prostaglandins.
      The COX enzyme exists in two forms, COX-1 and COX-2. Traditional NSAIDs are
      considered 'non-selective' because they inhibit both COX-1 and COX-2 enzymes.
      More selective NSAIDs that solely target COX-2 enzymes (COX-2-specific
      inhibitors) were launched in 1999 with the aim of reducing side effects commonly
      reported in association with NSAIDs, such as indigestion, headaches and
      drowsiness. OBJECTIVES: To determine the effectiveness and safety of NSAIDs in
      the treatment of primary dysmenorrhoea. SEARCH METHODS: We searched the following
      databases in January 2015: Cochrane Menstrual Disorders and Subfertility Group
      Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL,
      November 2014 issue), MEDLINE, EMBASE and Web of Science. We also searched
      clinical trials registers (ClinicalTrials.gov and ICTRP). We checked the
      abstracts of major scientific meetings and the reference lists of relevant
      articles. SELECTION CRITERIA: All randomised controlled trial (RCT) comparisons
      of NSAIDs versus placebo, other NSAIDs or paracetamol, when used to treat primary
      dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two review authors independently
      selected the studies, assessed their risk of bias and extracted data, calculating
      odds ratios (ORs) for dichotomous outcomes and mean differences for continuous
      outcomes, with 95% confidence intervals (CIs). We used inverse variance methods
      to combine data. We assessed the overall quality of the evidence using GRADE
      methods. MAIN RESULTS: We included 80 randomised controlled trials (5820 women).
      They compared 20 different NSAIDs (18 non-selective and two COX-2-specific)
      versus placebo, paracetamol or each other. NSAIDs versus placeboAmong women with
      primary dysmenorrhoea, NSAIDs were more effective for pain relief than placebo
      (OR 4.37, 95% CI 3.76 to 5.09; 35 RCTs, I(2) = 53%, low quality evidence). This
      suggests that if 18% of women taking placebo achieve moderate or excellent pain
      relief, between 45% and 53% taking NSAIDs will do so.However, NSAIDs were
      associated with more adverse effects (overall adverse effects: OR 1.29, 95% CI
      1.11 to 1.51, 25 RCTs, I(2) = 0%, low quality evidence; gastrointestinal adverse
      effects: OR 1.58, 95% CI 1.12 to 2.23, 14 RCTs, I(2) = 30%; neurological adverse
      effects: OR 2.74, 95% CI 1.66 to 4.53, seven RCTs, I(2) = 0%, low quality
      evidence). The evidence suggests that if 10% of women taking placebo experience
      side effects, between 11% and 14% of women taking NSAIDs will do so. NSAIDs
      versus other NSAIDsWhen NSAIDs were compared with each other there was little
      evidence of the superiority of any individual NSAID for either pain relief or
      safety. However, the available evidence had little power to detect such
      differences, as most individual comparisons were based on very few small trials.
      Non-selective NSAIDs versus COX-2-specific selectorsOnly two of the included
      studies utilised COX-2-specific inhibitors (etoricoxib and celecoxib). There was
      no evidence that COX-2-specific inhibitors were more effective or tolerable for
      the treatment of dysmenorrhoea than traditional NSAIDs; however data were very
      scanty. NSAIDs versus paracetamolNSAIDs appeared to be more effective for pain
      relief than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, three RCTs, I(2) = 0%, low
      quality evidence). There was no evidence of a difference with regard to adverse
      effects, though data were very scanty.Most of the studies were commercially
      funded (59%); a further 31% failed to state their source of funding. AUTHORS'
      CONCLUSIONS: NSAIDs appear to be a very effective treatment for dysmenorrhoea,
      though women using them need to be aware of the substantial risk of adverse
      effects. There is insufficient evidence to determine which (if any) individual
      NSAID is the safest and most effective for the treatment of dysmenorrhoea. We
      rated the quality of the evidence as low for most comparisons, mainly due to poor
      reporting of study methods.

PMID- 26224323
TI  - Complicated vascular access port removals: incidence, antecedents and avoidance.
AB  - PURPOSE: Port removal is usually a straightforward procedure delegated to
      trainees. However, some port removals are complicated by central venous catheter
      (CVC) fragmentation, a challenge for even experienced surgeons. This study aimed
      to determine the incidence of, and risk factors for, complicated port removal in
      children. METHODS: A single-centre study assessed the outcome of removal for all
      paediatric ports inserted from 1996 to 2012. Data were recorded detailing
      patient, insertion, device and removal characteristics. Risk factors for
      complicated removals were scrutinised using Chi-square tests; p < 0.05
      significant. RESULTS: Of 628 ports inserted from 1996 to 2012, 443 were
      subsequently removed at the same centre. 8/443 (1.8%) removals were complicated
      by CVC fragmentation, a median of 3.3 (2.4-3.9) years after insertion. Of
      complicated cases, 8/8 underwent formal neck dissection, 3/8 intravascular
      dissection, and 1/8 endovascular retrieval. 2/8 cases have retained intravascular
      CVC fragments. Risk factors for complication were CVC caliber <6Fr (p < 0.001)
      and use duration >2 years (p < 0.001). CONCLUSION: Greatest care and senior
      supervision should be ensured when removing ports with CVC caliber <6Fr and/or >2
      years since insertion. However, complications also occur with larger CVCs or
      after shorter durations. Therefore, the key to avoiding complicated port removal
      may simply be: preparation, preparation, neck preparation.

PMID- 26224324
TI  - Association between DEFB103 gene copy number variation and ankylosing
      spondylitis: a case-control study.
AB  - In this brief communication, we investigate the role of DEFB103 gene copy number
      variation (CNV) in ankylosing spondylitis (AS) susceptibility. A total of 807
      Chinese individuals including 406 AS patients and 401 controls were enrolled. The
      DEFB103 copy number was measured by two sets of probes to obtain a stable result
      in a custom-by-design Multiplex AccuCopy(TM) kit (Genesky Biotechnologies Inc.,
      Shanghai, China) based on a multiplex fluorescence competitive polymerase chain
      reaction (PCR) principle. The copy number of DEFB103 ranged from 2 to 6 in both
      AS patients and controls. Mann-Whitney U test and chi-squared test were performed
      to analyze the difference of DEFB103 copy number between AS patients and controls
      while no statistical difference has been found. We considered the copy number of
      DEFB103 gene may not associate with susceptibility to AS. 

PMID- 26224325
TI  - Rediscovery of Good-Turing estimators via Bayesian nonparametrics.
AB  - The problem of estimating discovery probabilities originated in the context of
      statistical ecology, and in recent years it has become popular due to its
      frequent appearance in challenging applications arising in genetics,
      bioinformatics, linguistics, designs of experiments, machine learning, etc. A
      full range of statistical approaches, parametric and nonparametric as well as
      frequentist and Bayesian, has been proposed for estimating discovery
      probabilities. In this article, we investigate the relationships between the
      celebrated Good-Turing approach, which is a frequentist nonparametric approach
      developed in the 1940s, and a Bayesian nonparametric approach recently introduced
      in the literature. Specifically, under the assumption of a two parameter Poisson
      Dirichlet prior, we show that Bayesian nonparametric estimators of discovery
      probabilities are asymptotically equivalent, for a large sample size, to suitably
      smoothed Good-Turing estimators. As a by-product of this result, we introduce and
      investigate a methodology for deriving exact and asymptotic credible intervals to
      be associated with the Bayesian nonparametric estimators of discovery
      probabilities. The proposed methodology is illustrated through a comprehensive
      simulation study and the analysis of Expressed Sequence Tags data generated by
      sequencing a benchmark complementary DNA library. 

PMID- 26224326
TI  - The geometric phase controls ultracold chemistry.
AB  - The geometric phase is shown to control the outcome of an ultracold chemical
      reaction. The control is a direct consequence of the sign change on the
      interference term between two scattering pathways (direct and looping), which
      contribute to the reactive collision process in the presence of a conical
      intersection (point of degeneracy between two Born-Oppenheimer electronic
      potential energy surfaces). The unique properties of the ultracold energy regime
      lead to an effective quantization of the scattering phase shift enabling maximum
      constructive or destructive interference between the two pathways. By taking the
      O+OH->H+O2 reaction as an illustrative example, it is shown that inclusion of the
      geometric phase modifies ultracold reaction rates by nearly two orders of
      magnitude. Interesting experimental control possibilities include the application
      of external electric and magnetic fields that might be used to exploit the
      geometric phase effect reported here and experimentally switch on or off the
      reactivity. 

PMID- 26224328
TI  - Probing the Catalytic Mechanism Involved in the Isocitrate Lyase Superfamily:
      Hybrid Quantum Mechanical/Molecular Mechanical Calculations on 2,3-Dimethylmalate
      Lyase.
AB  - The isocitrate lyase (ICL) superfamily catalyzes the cleavage of the C(2)-C(3)
      bond of various alpha-hydroxy acid substrates. Members of the family are found in
      bacteria, fungi, and plants and include ICL itself, oxaloacetate hydrolase (OAH),
      2-methylisocitrate lyase (MICL), and (2R,3S)-dimethylmalate lyase (DMML) among
      others. ICL and related targets have been the focus of recent studies to treat
      bacterial and fungal infections, including tuberculosis. The catalytic process by
      which this family achieves C(2)-C(3) bond breaking is still not clear. Extensive
      structural studies have been performed on this family, leading to a number of
      plausible proposals for the catalytic mechanism. In this paper, we have applied
      quantum mechanical/molecular mechanical (QM/MM) methods to the most recently
      reported family member, DMML, to assess whether any of the mechanistic proposals
      offers a clear energetic advantage over the others. Our results suggest that
      Arg161 is the general base in the reaction and Cys124 is the general acid, giving
      rise to a rate-determining barrier of approximately 10 kcal/mol. 

PMID- 26224327
TI  - Induced pluripotent stem cell technology for dissecting the cancer epigenome.
AB  - Cancer arises through the accumulation of both genetic and epigenetic
      alterations. Although the causal role of genetic mutations on cancer development
      has been established in vivo, similar evidence for epigenetic alterations is
      limited. Moreover, mutual interactions between genetic mutations and epigenetic
      alterations remain unclear. Cellular reprogramming technology can be used to
      actively modify the epigenome without affecting the underlying genomic sequences.
      Here we introduce recent studies that have utilized this property for cancer
      research. We propose that just as it has potential for regenerative medicine and
      disease modeling, cell reprogramming could also be a powerful tool for dissecting
      the role of the cancer epigenome in the development and maintenance of cancer
      cells. 

PMID- 26224329
TI  - Neutrophil-to-lymphocyte ratio: an inflammation marker related to cardiovascular
      risk in children.
AB  - Low-grade chronic inflammation plays a pathogenic role in cardiovascular disease.
      An increase in the ratio of circulating neutrophils to lymphocytes (N/L ratio)
      may serve as a marker of cardiovascular risk in adults. It was the study
      objective to study whether N/L ratio associates with vascular parameters in
      children. Subjects were 501 prepubertal and early pubertal Caucasian children
      (mean age 8.0 years; mean body mass index (BMI) Z-score 0.2 +/- 0.9; 266 boys and
      235 girls) recruited within an ongoing population-based study. The subjects were
      stratified into three groups according to age. Neutrophil, lymphocyte, BMI, waist
      circumference, systolic blood pressure (SBP) and carotid intima-media thickness
      (cIMT), assessed in all children. The N/L ratio, derived from the absolute
      neutrophil and lymphocyte counts. In children aged < 7 years (n=190, all
      prepubertal), no associations were observed between N/L ratio and either
      anthropometric or cardiovascular parameters. In children aged 7-9 years (n=171,
      1.7% early pubertal), higher N/L ratio associated with higher BMI Z-score and
      waist circumference (p=0.008 to p < 0.0001). In children aged >9 years (n=140,
      29.2% early pubertal), N/L ratio associated again with BMI Z-score and waist
      circumference and also positively with SBP and cIMT (all p=0.008 to p<0.0001).
      These associations remained significant in linear regression models following
      adjustment for possible confounding variables such as age, gender, fasting
      triglycerides, C-reactive protein and puberty (and for SBP and cIMT, adjustment
      also for BMI). In conclusion, our results provide the first evidence that a
      higher N/L ratio is associated with a less favourable cardiovascular profile in
      children and delineate the development of these associations from late childhood
      onwards.

PMID- 26224330
TI  - Dietary intake habits and controlled training on body composition and strength in
      elite female volleyball players during the season.
AB  - The purpose of this study was to assess dietary intake of elite female volleyball
      players (EFVPs, n = 22) during the first 11 weeks of the competitive season.
      Further, we compared findings for total energy intake and specific macronutrient
      distribution with the established recommendations for high-intensity athletes.
      Subjects also engaged in periodized training and we assessed changes in body
      composition (BC) and strength. Twenty-two EFVPs had dietary intake (7-day dietary
      recall and food-frequency questionnaire), BC (body mass index (BMI), body fat
      percentage, fat mass, muscle mass), and 1-repetition maximum (1RM) strength
      (bench press, military press, back squat, power clean, clean and jerk, pull-over)
      assessed at baseline (T0, before preseason) and 11 weeks later (T11). Athletes
      consumed less total kilocalories and carbohydrates (CHO) compared with
      established recommendations (total kilocalories: 40.7 +/- 5.2 kcal/(kg . day)(-1)
      vs. RECOMMENDATIONS: 50-80 kcal/(kg . day)(-1); CHO: 4.3 +/- 0.6 g/(kg . day)(-1)
      vs. RECOMMENDATIONS: 5-8 g/(kg . day)(-1)). Further, subjects consumed greater
      protein (2.1 +/- 0.4 g/(kg . day)(-1)) compared with recommendations (1.6-1.8
      g/(kg . day)(-1)) and greater fat (36.1 +/- 4.6% of total kilocalories) than
      recommendations (20%-35% of total kilocalories). There were improvements (p <
      0.05) in BC from T0-T11 (body fat percentage: 17.9% +/- 4.2%-16.8% +/- 3.6%, 
      4.7% +/- 7.4%; fat mass: 12.7 +/- 4.2-11.9 +/- 3.8 kg, -4.0% +/- 9.2%; muscle
      mass: 42.8% +/- 3.4%-43.3% +/- 3.0%, +1.3 +/- 3.1%) and 1RM strength (bench
      press: 39.1 +/- 4.5-43.4 +/- 4.9 kg; +11.4% +/- 9.3%; clean and jerk: 29.7 +/-
      6.3-34 +/- 5.8 kg; +17.7% +/- 23.8%); however, there was no change (p > 0.05) in
      BMI or military press and pull-over. Back squat (p = 0.054; +33.0% +/- 83.7%) and
      power clean (p = 0.056; +26.2% +/- 49.0%) increases approached significance. Our
      findings indicate that EFVPs improved BC and strength despite a dietary intake
      different from recommendations. This is possibly due to different substrate
      utilization during exercise in females versus males, thus new recommendations
      should be considered for high-intensity athletes, which are sex-specific.

PMID- 26224331
TI  - Transcriptional profiling of macrophages derived from monocytes and iPS cells
      identifies a conserved response to LPS and novel alternative transcription.
AB  - Macrophages differentiated from human induced pluripotent stem cells (IPSDMs) are
      a potentially valuable new tool for linking genotype to phenotype in functional
      studies. However, at a genome-wide level these cells have remained largely
      uncharacterised. Here, we compared the transcriptomes of naive and
      lipopolysaccharide (LPS) stimulated monocyte-derived macrophages (MDMs) and
      IPSDMs using RNA-Seq. The IPSDM and MDM transcriptomes were broadly similar and
      exhibited a highly conserved response to LPS. However, there were also
      significant differences in the expression of genes associated with antigen
      presentation and tissue remodelling. Furthermore, genes coding for multiple
      chemokines involved in neutrophil recruitment were more highly expressed in
      IPSDMs upon LPS stimulation. Additionally, analysing individual transcript
      expression identified hundreds of genes undergoing alternative promoter and 3'
      untranslated region usage following LPS treatment representing a previously under
      appreciated level of regulation in the LPS response. 

PMID- 26224332
TI  - Therapeutic drug monitoring of cyclosporine and area under the curve prediction
      using a single time point strategy: appraisal using peak concentration data.
AB  - There is an ongoing debate on the use of a single concentration time point C2 for
      therapeutic drug monitoring (TDM) and exposure prediction for cyclosporine. The
      objective of the present work was to evaluate the relationship between the peak
      concentration (Cmax ) versus area under the curve (AUC) for cyclosporine. Using
      published data from renal transplant patients from an 8-12 week study with two
      formulations, a simple linear regression model represented by AUC - cyclosporine
      = Cmax - Cyclosporine * 3.9965 + 384.5 (r = 0.9647; p < 0.001) was developed.
      Using the regression equation, predictions of AUC from the reported Cmax data
      were performed; the fold difference between observed vs predicted AUC was
      computed and the root mean square error for the prediction was calculated. While
      all but one of the predicted AUCs were contained within a 0.5-2-fold difference
      (99.1%), a greater proportion of the AUC values were predicted within a narrower
      range of 0.75 to 1.5-fold difference (78.2%), suggesting the utility of Cmax as
      the right surrogate for predicting the AUC for cyclosporine with a correlation
      coefficient of 0.8698 (n = 126; p < 0.001) and a RMSE of 26.2%. Since the time to
      Cmax generally varies from 1 to 2 h, although the results validate the use of C2,
      there may be an opportunity to explore the suitability of C1 or C1.5 in a
      prospective study for the purpose of TDM and AUC prediction of cyclosporine.

PMID- 26224333
TI  - Axon terminals from the nucleus isthmi pars parvocellularis control the ascending
      retinotectofugal output through direct synaptic contact with tectal ganglion cell
      dendrites.
AB  - The optic tectum in birds and its homologue the superior colliculus in mammals
      both send major bilateral, nontopographic projections to the nucleus rotundus and
      caudal pulvinar, respectively. These projections originate from widefield tectal
      ganglion cells (TGCs) located in layer 13 in the avian tectum and in the lower
      superficial layers in the mammalian colliculus. The TGCs characteristically have
      monostratified arrays of brush-like dendritic terminations and respond mostly to
      bidimensional motion or looming features. In birds, this TGC-mediated tectofugal
      output is controlled by feedback signals from the nucleus isthmi pars
      parvocellularis (Ipc). The Ipc neurons display topographically organized axons
      that densely ramify in restricted columnar terminal fields overlapping various
      neural elements that could mediate this tectofugal control, including the retinal
      terminals and the TGC dendrites themselves. Whether the Ipc axons make synaptic
      contact with these or other tectal neural elements remains undetermined. We
      double labeled Ipc axons and their presumptive postsynaptic targets in the tectum
      of chickens (Gallus gallus) with neural tracers and performed an ultrastructural
      analysis. We found that the Ipc terminal boutons form glomerulus-like structures
      in the superficial and intermediate tectal layers, establishing asymmetric
      synapses with several dendritic profiles. In these glomeruli, at least two of the
      postsynaptic dendrites originated from TGCs. We also found synaptic contacts
      between retinal terminals and TGC dendrites. These findings suggest that, in
      birds, Ipc axons control the ascending tectal outflow of retinal signals through
      direct synaptic contacts with the TGCs.

PMID- 26224334
TI  - Learning from the crowd while mapping to LOINC.
AB  - OBJECTIVE: To describe the perspectives of Regenstrief LOINC Mapping Assistant
      (RELMA) users before and after the deployment of Community Mapping features,
      characterize the usage of these new features, and analyze the quality of mappings
      submitted to the community mapping repository. METHODS: We evaluated Logical
      Observation Identifiers Names and Codes (LOINC) community members' perceptions
      about new "wisdom of the crowd" information and how they used the new RELMA
      features. We conducted a pre-launch survey to capture users' perceptions of the
      proposed functionality of these new features; monitored how the new features and
      data available via those features were accessed; conducted a follow-up survey
      about the use of RELMA with the Community Mapping features; and analyzed
      community mappings using automated methods to detect potential errors. RESULTS:
      Despite general satisfaction with RELMA, nearly 80% of 155 respondents to our pre
      launch survey indicated that having information on how often other users had
      mapped to a particular LOINC term would be helpful. During the study period, 200
      participants logged into the RELMA Community Mapping features an average of 610
      times per month and viewed the mapping detail pages a total of 6686 times. Fifty
      respondents (25%) completed our post-launch survey, and those who accessed the
      Community Mapping features unanimously indicated that they were useful. Overall,
      95.3% of the submitted mappings passed our automated validation checks.
      CONCLUSION: When information about other institutions' mappings was made
      available, study participants who accessed it agreed that it was useful and
      informed their mapping choices. Our findings suggest that a crowd-sourced
      repository of mappings is valuable to users who are mapping local terms to LOINC
      terms.

PMID- 26224335
TI  - Extracting relations from traditional Chinese medicine literature via
      heterogeneous entity networks.
AB  - OBJECTIVE: Traditional Chinese medicine (TCM) is a unique and complex medical
      system that has developed over thousands of years. This article studies the
      problem of automatically extracting meaningful relations of entities from TCM
      literature, for the purposes of assisting clinical treatment or poly-pharmacology
      research and promoting the understanding of TCM in Western countries. METHODS:
      Instead of separately extracting each relation from a single sentence or
      document, we propose to collectively and globally extract multiple types of
      relations (eg, herb-syndrome, herb-disease, formula-syndrome, formula-disease,
      and syndrome-disease relations) from the entire corpus of TCM literature, from
      the perspective of network mining. In our analysis, we first constructed
      heterogeneous entity networks from the TCM literature, in which each edge is a
      candidate relation, then used a heterogeneous factor graph model (HFGM) to
      simultaneously infer the existence of all the edges. We also employed a semi
      supervised learning algorithm estimate the model's parameters. RESULTS: We
      performed our method to extract relations from a large dataset consisting of more
      than 100,000 TCM article abstracts. Our results show that the performance of the
      HFGM at extracting all types of relations from TCM literature was significantly
      better than a traditional support vector machine (SVM) classifier (increasing the
      average precision by 11.09%, the recall by 13.83%, and the F1-measure by 12.47%
      for different types of relations, compared with a traditional SVM classifier).
      CONCLUSION: This study exploits the power of collective inference and proposes an
      HFGM based on heterogeneous entity networks, which significantly improved our
      ability to extract relations from TCM literature.

PMID- 26224336
TI  - Review and evaluation of electronic health records-driven phenotype algorithm
      authoring tools for clinical and translational research.
AB  - OBJECTIVE: To review and evaluate available software tools for electronic health
      record-driven phenotype authoring in order to identify gaps and needs for future
      development. MATERIALS AND METHODS: Candidate phenotype authoring tools were
      identified through (1) literature search in four publication databases (PubMed,
      Embase, Web of Science, and Scopus) and (2) a web search. A collection of tools
      was compiled and reviewed after the searches. A survey was designed and
      distributed to the developers of the reviewed tools to discover their
      functionalities and features. RESULTS: Twenty-four different phenotype authoring
      tools were identified and reviewed. Developers of 16 of these identified tools
      completed the evaluation survey (67% response rate). The surveyed tools showed
      commonalities but also varied in their capabilities in algorithm representation,
      logic functions, data support and software extensibility, search functions, user
      interface, and data outputs. DISCUSSION: Positive trends identified in the
      evaluation included: algorithms can be represented in both computable and human
      readable formats; and most tools offer a web interface for easy access. However,
      issues were also identified: many tools were lacking advanced logic functions for
      authoring complex algorithms; the ability to construct queries that leveraged un
      structured data was not widely implemented; and many tools had limited support
      for plug-ins or external analytic software. CONCLUSIONS: Existing phenotype
      authoring tools could enable clinical researchers to work with electronic health
      record data more efficiently, but gaps still exist in terms of the
      functionalities of such tools. The present work can serve as a reference point
      for the future development of similar tools.

PMID- 26224337
TI  - Teneligliptin, a Dipeptidyl Peptidase-4 Inhibitor, Improves Early-Phase Insulin
      Secretion in Drug-Naive Patients with Type 2 Diabetes.
AB  - INTRODUCTION: It remains unknown whether dipeptidyl peptidase-4 (DPP-4)
      inhibitors improve early-phase insulin secretion in Japanese patients with type 2
      diabetes (T2D), a disease characterized by impaired insulin secretion. We
      investigated the changes in insulin secretion before and after treatment with the
      DPP-4 inhibitor teneligliptin in patients with T2D with a low insulinogenic index
      (IGI) determined by the oral glucose tolerance test (OGTT). METHODS: An open
      label, prospective clinical study was conducted. Thirteen drug-naive patients
      (mean age 55.5 +/- 3.9 years) with T2D underwent OGTT before and after
      teneligliptin 20 mg/day monotherapy. Plasma levels of glucose (PG), insulin, and
      C-peptide were measured at 0, 30, 60, 90, and 120 min after glucose loading in
      the OGTT. Homeostasis model assessment (HOMA)-beta, IGI, and the total or
      incremental area under the curve (AUC) for PG and insulin were measured.
      AUC120min for the secretory units of islets in transplantation (SUIT) index was
      also measured. RESULTS: HbA1c significantly decreased from 8.3 +/- 0.4% at
      baseline to 6.3 +/- 0.2% after 12 weeks of teneligliptin treatment (p < 0.05).
      Incremental AUC120min PG also significantly decreased, and beta-cell function
      assessed by IGI30min, AUC120min insulin, and the AUC120min SUIT index
      significantly increased (0.16 +/- 0.05 vs. 0.28 +/- 0.06, 2692 +/- 333 uU.2h/mL
      vs. 3537 +/- 361 uU.2h/mL, and 4261 +/- 442 vs. 8290 +/- 1147, respectively; all
      p < 0.05). HOMA-beta was unchanged. The reduction in incremental AUC120min PG was
      significantly associated with the augmentation of IGI30min and the AUC120min SUIT
      index. No severe adverse events were observed. CONCLUSIONS: Twelve weeks of
      teneligliptin treatment improved IGI30min, AUC120min, and the SUIT index in drug
      naive Japanese patients with T2D.

PMID- 26224338
TI  - Mid-term haemodynamic and clinical results after aortic valve replacement using
      the Freedom Solo stentless bioprosthesis versus the Carpentier Edwards Perimount
      stented bioprosthesis.
AB  - OBJECTIVES: The aim of this study was to investigate the mid-term haemodynamic
      and clinical results after aortic valve replacement (AVR) using the Sorin Freedom
      Solo (SFS) stentless bioprosthesis, compared with the standard Carpentier Edwards
      Perimount (CEP) stented bioprosthesis. METHODS: In this retrospective cohort
      study of prospectively collected data, 116 patients were included in the SFS
      group (53 males; median age 74 years, range 56-85 years), and 122 patients in the
      CEP group (85 males; median age 73 years, range 43-88 years) between July 2007
      and January 2013. Echocardiography was performed at 6 weeks after surgery in our
      centre, and the most recent echocardiography (in our centre or in referring
      cardiology departments) was requested. Between September 2013 and April 2014, all
      patients were called by the same researcher to gain clinical follow-up data.
      RESULTS: Mid-term mortality was 16.4% in the SFS group (19 patients) and 21.3% in
      the CEP group (26 patients); (P = 0.3). The mean transvalvular gradient was 7.4
      +/- 3.1 mmHg in the SFS group, and 11.6 +/- 3.2 mmHg in the CEP group at 6 weeks
      postoperatively (P < 0.001). When stratified by labelled valve size, mean
      gradients were significantly lower in the SFS group for every size (P <= 0.03).
      After 3.3 +/- 1.4 years of follow-up, the mean gradient was still significantly
      lower in the SFS group than that in the CEP group (P < 0.001). Clinical follow-up
      showed relatively low complication rates. CONCLUSION: These data suggest that the
      Sorin Freedom Solo stentless bioprosthesis is as safe as the Carpentier Edwards
      bioprosthesis, and provides better short- and mid-term haemodynamic performance
      than the Carpentier Edwards bioprosthesis.

PMID- 26224339
TI  - Aortic events after isolated aortic valve replacement for bicuspid aortic valve
      root phenotype: echocardiographic follow-up study.
AB  - OBJECTIVES: Various forms of bicuspid aortic valve (BAV) aortopathy exist, and
      the optimal treatment for the different subgroups is insufficiently defined. We
      aimed to analyse the risk of adverse aortic events after aortic valve replacement
      (AVR) for BAV insufficiency and concomitant mild-to-moderate dilatation of the
      aortic root (i.e. BAV root phenotype). METHODS: A total of 56 consecutive
      patients (mean age 47 +/- 11 years, 95% men) with BAV insufficiency and a root
      diameter of 40-50 mm underwent AVR surgery from 1995 to 2008. All patients, as
      identified from our institutional BAV database, had a dilated aortic annulus
      (i.e. defined as valve prosthesis size >=27 mm) without aortic stenosis (i.e.
      mean gradient <=20 mmHg). Patients who underwent concomitant aortic surgery were
      excluded. Follow-up (622 patient-years) including echocardiography data was
      available for all patients. Aortic events were defined as the need for proximal
      aortic surgery, the occurrence of aortic dissection/rupture, echocardiographic
      evidence of increasing aortic root diameter/occurrence of late paravalvular
      leakage or sudden death during follow-up. RESULTS: Actuarial survival was 90% at
      10 years and 78% at 15 years. Adverse aortic events occurred in 19 (34%) study
      patients. Redo aortic surgery was performed in 6 patients (11%), 2 of which were
      for aortic dissection. Four patients (7%) suffered sudden cardiac death.
      Moreover, follow-up echocardiography revealed a significant, progressive
      enlargement of the aortic root diameter in 7 (13%) patients and occurrence of
      late de novo paravalvular leakage in 2 (3%) patients. The resultant freedom from
      aortic events was 81% at 10 years and 51% at 15 years. CONCLUSIONS: Patients with
      a BAV root phenotype are at significant risk of aortic events after isolated AVR.
      Simultaneous root/ascending aortic surgery should be strongly considered in such
      patients.

PMID- 26224340
TI  - Exacerbation of bleomycin-induced injury by lipopolysaccharide in mice:
      establishment of a mouse model for acute exacerbation of interstitial lung
      diseases.
AB  - OBJECTIVES: Interstitial lung disease (ILD) is sometimes seen in patients with
      primary lung cancer. Therapeutic interventions for lung cancer patients with ILD
      sometimes provoke acute exacerbation (AE) of pre-existing lung disease. Although
      postoperative AE after lung resection is a potentially fatal complication,
      prophylactic treatments have yet to be established. Prophylaxis for postoperative
      AE is imperative for thoracic surgeons. However, no animal models for preclinical
      research into postoperative management and prophylactic interventions for AE of
      ILD have been developed. The objective of this study was to establish a new mouse
      model of AE of ILD, for further investigation of prophylactic interventions.
      METHODS: C57BL/6 mice were intratracheally administered bleomycin (BLM, 1 mg/kg)
      or saline on Day 0 to induce pulmonary fibrosis, and lipopolysaccharide (LPS, 0.5
      mg/kg) or saline to induce inflammatory stimulation on Day 7. Mice were divided
      into four groups: control group; LPS group; BLM group and BLM + LPS group.
      Histological changes and computed tomography (CT) images of the lung, lung water
      content, oxygen partial pressure (pO2) of arterial blood and cell counts and
      inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were assessed
      on Day 8. Survival rates were also determined. RESULTS: In the BLM + LPS group,
      chest CT showed diffuse ground-glass opacities, and pO2 was significantly
      decreased. The most severe inflammatory reaction was evident in the BLM + LPS
      group, with increased infiltrating cells on histopathology and increased lung
      water content. Total cell and neutrophil counts and levels of cytokines such as
      monocyte chemoattractant protein-1, interleukin-6 and keratinocyte
      chemoattractant in the BALF were significantly elevated in the BLM + LPS group.
      These findings mimic human AE of ILD. Furthermore, survival curves demonstrated
      that the BLM + LPS group had the lowest survival rate among all groups.
      CONCLUSIONS: A new mouse model of AE of ILD was developed. This model represents
      an attractive experimental method for preclinical research of postoperative
      management and prophylactic interventions for AE of ILD in lung cancer patients.

PMID- 26224341
TI  - Validity of Self-Report Data in Hypertension Research: Findings From The Study on
      Global Ageing and Adult Health.
AB  - Several studies indicate little congruence between self-report and biometric
      data, yet very few have examined the reasons for such differences. This paper
      contributes to the limited but growing body of literature that tracks
      inconsistent reports of hypertension using data from the Study on Global Ageing
      and Adult Health (SAGE). Focusing on five countries with different levels of
      development (Ghana, China, India, South Africa, and Russia), this study offers a
      comparative perspective that is missing in the literature. Data were obtained
      from wave 1 of SAGE collected in 2007/2008. A multinomial logit model was used to
      examine the effects of demographic and socioeconomic variables on the likelihood
      of respondents self-reporting that they are not hypertensive when their biometric
      data show otherwise. The authors also model the likelihood of respondents self
      reporting that they are hypertensive when in fact their biometric data show they
      are not. Socioeconomic and demographic variables were shown to be significantly
      associated with inconsistent reporting of hypertension. For instance, it was
      observed that wealth was associated with a lower likelihood of self-reporting
      that one is not hypertensive when their biometric data indicate otherwise.
      Tracking such inconsistent reports is crucial to minimizing measurement errors
      and generating unbiased and more precise parameter estimates in hypertension
      research. 

PMID- 26224343
TI  - Compelling evidence linking sugary drinks with diabetes.

PMID- 26224344
TI  - Development of shampoo, soap and ointment formulated by green synthesised silver
      nanoparticles functionalised with antimicrobial plants oils in veterinary
      dermatology: treatment and prevention strategies.
AB  - Many scientists have focused their research on the role of nanotechnology for the
      control of human pathogens, but there are also many topical pathogens present in
      animals, which infect animals and transfer to humans. Topical therapy is
      extremely important for the management of dermatological condition in animals.
      Therefore, the present study aims to evaluate the efficacy of biogenic silver
      nanoparticles (AgNPs) in combination with herbal oils against animal skin
      infections which may be responsible for causing infections in human beings. Here,
      the authors synthesised and characterised the AgNPs from Azadirachta indica. The
      oils were extracted from medicinal plants including Cymbopogon citratus,
      Cymbopogon martini, Eucalyptus globules, A. indica and Ocimum sanctum and the
      antifungal and antibacterial activity of plant oils along with AgNPs were
      evaluated. An excision wound model was used for the study of wound healing
      activity in rabbits. AgNPs functionalised oil has demonstrated remarkable
      antimicrobial activity against pathogens present on the skin of animals. The nano
      functionalised antimicrobial oils were used in the formulation of shampoo, soap
      and ointment for veterinary dermatology. Antimicrobial products of plant origin
      with AgNPs are valuable, safe and have a specific role in controlling diseases.
      The authors believe that this approach will be a good alternative therapy to
      solve the continuous antibiotic resistance developed by many bacterial pathogens
      and will be utilised in various animal contacting areas in medicine. 

PMID- 26224342
TI  - Integrating GRK2 and NFkappaB in the Pathophysiology of Cardiac Hypertrophy.
AB  - G protein coupled receptor kinase type 2 (GRK2) plays an important role in the
      development and maintenance of cardiac hypertrophy and heart failure even if its
      exact role is still unknown. In this study, we assessed the effect of GRK2 on the
      regulation of cardiac hypertrophy. In H9C2 cells, GRK2 overexpression increased
      atrial natriuretic factor (ANF) activity and enhanced phenylephrine-induced ANF
      response, and this is associated with an increase of NFkappaB transcriptional
      activity. The kinase dead mutant and a synthetic inhibitor of GRK2 activity
      exerted the opposite effect, suggesting that GRK2 regulates hypertrophy through
      upregulation of NFkappaB activity in a phosphorylation-dependent manner. In two
      different in vivo models of left ventricle hypertrophy (LVH), the selective
      inhibition of GRK2 activity prevented hypertrophy and reduced NFkappaB
      transcription activity. Our results suggest a previously undisclosed role for
      GRK2 in the regulation of hypertrophic responses and propose GRK2 as potential
      therapeutic target for limiting LVH. 

PMID- 26224345
TI  - In vitro cytotoxic activity of chitosan-bullfrog oil microemulsion against
      melanoma cells.
AB  - Microemulsion-based animal oils, alone or associated with polymers have been
      extensively used in pharmacy, medicine and cosmetics, since the major lipid
      constituents of the oils show several biological activities. Despite showing
      antimicrobial activity, there are no reports in the literature regarding the
      effects of bullfrog oil on cytotoxic activity against tumor cells. The aim of the
      present study was to synthesize, characterise and evaluate the in vitro effects
      on melanoma cell line (B16F10) of bullfrog oil microemulsions associated or not
      with chitosan, surfactant and bullfrog oil (CSBO) and surfactant and bullfrog oil
      (SBO), respectively. The microemulsions were developed and their physical
      chemical characteristics were evaluated by light microscopy, dynamic light
      scattering, atomic force microscopy and zeta potential. The microemulsions showed
      regular spherical shapes, high polydispersity and excellent (+82.2 +/- 1.0 mV) to
      low (-16.0 +/- 0.5 mV), colloidal stability. The systems significantly decreased
      the in vitro cell viability of melanoma skin cancer by up to 90.2% (CSBO) and
      91.8% (SBO); while free bullfrog oil showed no effects. The results obtained from
      microemulsions of bullfrog oil indicate the potential of the microemulsions
      developed, alone or in combination with other chemotherapeutic agents, for future
      use in biomedical approaches aiming towards cancer therapy. 

PMID- 26224346
TI  - Fungal biomolecules assisted biosynthesis of Au-Ag alloy nanoparticles and
      evaluation of their catalytic property.
AB  - The catalytic reduction of methylene blue was studied using biosynthesised gold
      silver (Au-Ag) alloy nanoparticles (NPs). The fungal biomass of Trichoderma
      harzianum was used as a reducing and stabilising agent in the synthesis of Au-Ag
      alloy NPs. The synthesised NPs were well characterised by UV-vis spectroscopy,
      dynamic light scattering, X-ray diffraction, transmission electron microscopy,
      energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy.
      The plausible synthesis mechanism involved in the formation of Au-Ag alloy NPs
      was also discussed with diagrammatic representation. A series of experiments was
      performed to investigate the catalytic activity of the as-prepared Au-Ag alloy
      NPs and found that the alloy NPs show excellent catalytic activity. 

PMID- 26224347
TI  - Phoenix dactylifera (date palm) pit aqueous extract mediated novel route for
      synthesis high stable silver nanoparticles with high antifungal and antibacterial
      activity.
AB  - The biological synthesis of silver nanoparticles (AgNPs) was conducted using date
      palm pit aqueous extract. The first visible sign of the synthesis of AgNPs was
      the change in colour of reaction mixtures from yellowish to reddish brown. The
      resulting synthesised AgNPs were characterised using UV-visible spectroscopy, X
      ray diffraction (XRD), transmission electron microscopy (TEM) and dynamic light
      scattering (DLS). The UV-visible spectra gave surface plasmon resonance at 428
      nm. XRD confirmed that the silver particles formed in our experiments were in the
      form of nanocrystals. TEM images revealed the formation of AgNPs with spherical
      shape and sizes in the range between 1-40 nm. DLS showed nanoparticles with an
      average size of 27 nm. Fourier transform infrared spectroscopy indicated the role
      of different possible functional groups (carboxyl, amine, aromatic and hydroxyl)
      in the formation of AgNPs. AgNPs were stable at 28 degrees C in vitro for over a
      year without any precipitation or decreased production of antimicrobial effect.
      Then, the antifungal and antibacterial activities of synthesised AgNPs were
      investigated. The synthesised AgNPs showed significant inhibitory effects on
      Rhizoctonia solani (AG2_2) cultures, so that the concentration of 25 ug/ml
      prevented approximately 83% of the mycelium growth of the fungus. Then, the broth
      macro-dilution method was used for examining antibacterial effect of AgNPs. The
      minimum inhibitory concentration and minimum bactericide concentration against
      Klebsiella pneumonia (PCI 602) and Acinetobacter baumannii (ATCC 19606) were
      recorded as 1.56 and 3.12 ug/ml AgNPs, respectively. 

PMID- 26224348
TI  - Drug release, cell adhesion and wound healing evaluations of electrospun
      carboxymethyl chitosan/polyethylene oxide nanofibres containing phenytoin sodium
      and vitamin C.
AB  - In this work, N, O-carboxymethyl chitosan (CMCS) samples from virgin chitosan
      (CS) were synthesised and CMCS/polyethylene oxide (PEO) (50/50) blend nanofibrous
      samples were successfully electrospun from their aqueous solution. The
      electrospinning conditions to achieve smooth and fine diameter nanofibrous mats
      were optimised via D-optimal design approach. Afterwards, vitamin C and phenytoin
      sodium (PHT-Na) were added to these samples for producing wound dressing
      materials. H-nuclear magnetic resonance, scanning electron microscopy and Fourier
      transform infrared tests for the evaluation of functionalised CS, morphology and
      biodegradability studies of CMCS/PEO blend nanofibrous samples were applied. The
      kinetic and drug release mechanism for vitamin C and PHT-Na drug-loaded
      electrospun samples were also investigated by UV-vis spectrophotometer and high
      performance liquid chromatography, respectively. The results showed an
      approximately similar drug release rate of the two drugs and followed Higuchi's
      kinetic model. The stem cells viability and their adhesion on the surface of the
      samples containing PHT-Na and vitamin C were carried out using MTT assay and the
      best cells' biocompatibility was obtained using both drugs into the CMCS/PEO
      nanofibrous samples. Moreover, the in vivo animal wound model results revealed
      that the electrospun samples containing vitamin C and PHT-Na (1%) had a
      remarkable efficiency in the wounds' closure and their healing process compared
      with vitamin C/PHT-Na (50/50) ointment. Finally, the histology observations
      showed that the wound treated with optimised electrospun samples containing two
      drugs enabled regeneration of epidermis layers due to collagen fibres
      accumulation followed by granulating tissues formation without necrosis. 

PMID- 26224349
TI  - Facile and novel synthetic method to prepare nano molybdenum and its catalytic
      activity.
AB  - This study reports on a facile and economical synthetic method to prepare nano
      molybdenum by solid-state reaction technique. Metallic nano molybdenum was
      synthesised from molybdenum trioxide, molybdenum IV oxide and molybdenum VI oxide
      through thermal decomposition technique. Metallic nano molybdenum prepared from
      molybdenum IV oxide was used to study the catalytic effect of molybdenum
      nanoparticles on the growth of Anabaena sp. The increase in concentration of nano
      molybdenum from 0.1 to 100% in BG11 (N- Mo- + nano Mo) medium increases
      heterocyst frequency. The chlorophyll and protein content in Anabaena sp. was
      found to improve when compared with bulk molybdenum particles and showed a
      positive influence to be used as a nano nutrient for Anabaena sp.

PMID- 26224350
TI  - Detection and qualification of optimum antibacterial and cytotoxic activities of
      silver-doped bioactive glasses.
AB  - This study aims to detect the optimum antibacterial activity of silver-doped
      bioactive glasses (Ag-BGs) for prevention of post-transplant infections in tissue
      engineering. The results have shown that the Ag-BG samples had broad-spectrum
      antibacterial efficacy in an Ag concentration-dependent manner. The 2% Ag-BG had
      the highest effect during the first 10 min to 72 h. The minimum inhibitory
      concentration of 2% Ag-BG was estimated to be 2 mg/ml for Escherichia coli (E.
      coli) and Pseudomonas aeruginosa (P. aeruginosa) and 2.66 mg/ml for
      Staphylococcus aureus (S. aureus). A concentration of 0.5% Ag-BG repressed growth
      of E. coli after 1 h, but did not have any detectable antibacterial effect for
      longer periods. Evaluation of the effects of prepared Ag-BG on human osteoblast
      cells viability showed that 1 and 2% samples changed the cell proliferation rate
      in masses of more than 3.33 and 2 mg/ml, respectively. Moreover, in a typical
      manner, the release of Ag ions from the glass structure started immediately,
      continued steadily and affected bacterial growth when it reached its critical
      concentration in the medium. This systematic study can illustrate the optimum
      antibacterial property of the Ag-BG samples in masses of 3.33 and 2 mg/ml for 1
      and 2% Ag, respectively, for prevention of post-transplant infections. 

PMID- 26224351
TI  - Production of micro- and nanosilica from soil inhabiting Folsomia candida fed
      with treated rice husk.
AB  - Rice husk was employed as a source for producing silica micro- and nanoparticles
      through its digestion by soil fauna. Although many physicochemical methods for
      producing nanostructures have been studied, the biological processes remain
      mostly unexplored. Alkaline hydrogen peroxide with continuous control of reaction
      pH allowed removal of lignin bonds while preserving most of the cell wall and the
      silica present in the rice husk. The accessibility of lignocellulose was achieved
      without removing appreciable amounts of lignin, so this agricultural byproduct
      can be employed as feeding material for microarthropods Folsomia candida
      (Collembola). When these microarthropods are placed on a substrate of treated
      rice husk, more than 85% of degraded material is obtained, as compared to the
      untreated rice husk substrate, while the silica particles obtained show a slight
      decrease in average size. 

PMID- 26224352
TI  - Biological synthesis of manganese dioxide nanoparticles by Kalopanax pictus plant
      extract.
AB  - Manganese dioxide (MnO2) nanoparticles were synthesised by the reduction of
      potassium permanganate (KMnO4) using Kalopanax pictus leaf extract at room
      temperature. A transparent dark-brown colour appeared after the addition of K.
      pictus leaf extract to the solution of permanganate. The time course of the
      reduction of KMnO4and synthesis of MnO2 nanoparticles was monitored by means of
      UV-Vis spectra. The reduction of KMnO4occurred after addition of plant extract
      with disappearance of KMnO4specific peaks and emergence of peak specific for
      MnO2nanoparticles. MnO2nanoparticles showed absorption maxima at 404 nm. The
      electron dispersive X-ray spectroscopy analyses confirmed the presence of Mn and
      O in the sample. X-ray photoelectron spectroscopy revealed characteristic binding
      energies for MnO2nanoparticles. Transmission electron microscopy micrographs
      revealed presence of uniformly dispersed spherical shaped particles with average
      size of 19.2 nm. The selected area electron diffraction patterns revealed the
      crystalline nature of MnO2nanoparticles. Fourier transform-infrared spectroscopy
      spectra of pure MnO2show the occurrence of O-Mn-O vibrational mode at around 518
      cm-1. The phyto-synthesised MnO2nanoparticles showed degradation ability of dyes
      (congo red and safranin O) similar to chemically synthesised MnO2nanoparticles.
      This study shows simple and eco-friendly synthesis of MnO2nanoparticles by plant
      extract and their utilisation for dye degradation for the first time.

PMID- 26224353
TI  - Design of a DNA-based reversible arithmetic and logic unit.
AB  - Owing to the emergence of better characteristics such as parallelism, low power
      consumption and data compactness, DNA computing has drawn great attention in
      recent years. In this study, the authors realise an arithmetic and logic unit
      (ALU) using deoxyribonucleic acid (DNA). Inputs and outputs of the proposed ALU
      keep the logical reversibility in computation processes. The proposed ALU is
      capable of performing four logical (AND, OR, EX-OR and NOT) with three arithmetic
      (addition, subtraction and multiplication) operations. They use DNA-based
      multiplexer to carry out final output. Compared to silicon-based computation, the
      proposed ALU is faster and requires less space and power due to parallelism,
      replication properties, compactness and formation of DNA strands. However,
      compared to one existing DNA-based system, fewer signals are required in each
      step. Besides, another existing DNA-based ALU requires five complex biological
      steps to compute, whereas the proposed ALU requires three biological steps. Also,
      the time complexities of that existing system are O(mln2n) for addition and
      subtraction operations; O(m) for logical operations and O(m(ln2n)(2)) for
      multiplication operation, while the proposed system has O(1) for logical
      operations and O(n) for others; here n is the number of bits and m is the number
      of test tubes for operands.

PMID- 26224354
TI  - In vitro effect of biogenic silver nanoparticles on sterilisation of tobacco leaf
      explants and for higher yield of protoplasts.
AB  - Isolation of protoplasts from leaves is useful in plant research. The standard
      reference methods for isolation of protoplasts are tedious, cause cell damage,
      are low-yield, time consuming and prone to microbial contamination. To overcome
      this problem, the authors used silver nanoparticles (AgNPs) for the control of
      microbial contamination and with low concentration of enzyme mixture for rapid
      release of protoplasts. The leaf explants were sterilised with 95% ethanol for 30
      s followed by biologically synthesised AgNPs (1, 5, 10 and 15 mg/l) for 10 to 20
      min. The authors found that 10 mg/l concentration of AgNPs treatment on explants
      showed remarkable inhibitory effect on microbial contamination with high level of
      tolerance. Moreover, during protoplasts isolation, the addition of 10 mg/l AgNPs
      in leaf incubation buffer yielded 34% viable protoplasts in 3 h. This is the
      first report of AgNPs synthesis from waste plant medium, which was applied for
      the sterilisation of explants and rapid isolation of protoplasts. 

PMID- 26224355
TI  - SuRankCo: supervised ranking of contigs in de novo assemblies.
AB  - BACKGROUND: Evaluating the quality and reliability of a de novo assembly and of
      single contigs in particular is challenging since commonly a ground truth is not
      readily available and numerous factors may influence results. Currently available
      procedures provide assembly scores but lack a comparative quality ranking of
      contigs within an assembly. RESULTS: We present SuRankCo, which relies on a
      machine learning approach to predict quality scores for contigs and to enable the
      ranking of contigs within an assembly. The result is a sorted contig set which
      allows selective contig usage in downstream analysis. Benchmarking on datasets
      with known ground truth shows promising sensitivity and specificity and favorable
      comparison to existing methodology. CONCLUSIONS: SuRankCo analyzes the
      reliability of de novo assemblies on the contig level and thereby allows quality
      control and ranking prior to further downstream and validation experiments.

PMID- 26224356
TI  - Maternal obesity regulates gene expression in the hearts of offspring.
AB  - BACKGROUND AND AIMS: Growing evidence suggests maternal obesity leads to adverse
      outcomes for offspring, including increased cardiovascular disease (CVD).
      Alterations in taste preferences of offspring from mothers consuming a high fat
      diet (HFD) have also been reported. Given recent reports describing cardiac taste
      receptors, we examined whether the expression of umami and bitter taste receptors
      is modulated by maternal obesity, and compared this with the physiological
      challenge of maternal exercise. METHODS AND RESULTS: Female Sprague-Dawley rats
      were fed chow (C) or HFD (F) and half of each were provided with a running wheel
      to enable voluntary exercise (CE or FE), the others remaining sedentary (CS or
      FS). Two pups from each mother were killed at postnatal day 19. Both lean and
      obese dams undertook similar amounts of exercise (8.1 +/- 2.4 vs 5.1 +/- 1.5 km).
      Maternal obesity increased offspring body weight, adiposity, net and weight
      corrected heart ventricle weight, with no effect of exercise. Maternal obesity
      also increased offspring plasma leptin concentrations, which were normalised by
      maternal exercise. Cardiac ventricle mRNA expression of bitter taste receptors,
      beta-adrenoceptor (Adrbk1) and angiotensin II receptor type 1a (Agtr1a) were
      significantly decreased in response to maternal obesity, with maternal exercise
      decreasing Agtr1a in FE offspring. No changes in umami receptors were observed.
      FTO mRNA expression was down-regulated by maternal HFD with an up-regulation in
      offspring of CE mothers. CONCLUSION: Maternal obesity affected the expression of
      bitter taste receptors and other genes in the heart ventricle, potentially
      implicating these genes in the development of CVD associated with maternal
      obesity.

PMID- 26224357
TI  - Functionalized corannulene carbocations: a structural overview.
AB  - A detailed structural overview of a family of bowl-shaped polycyclic aromatic
      carbocations of the type [C20 H10 R](+) with different R functionalities tethered
      to the interior surface of corannulene (C20 H10 ) is provided. Changing the
      identity of the surface-bound groups through alkyl chains spanning from one to
      four carbon atoms and incorporating a different degree of halogenation has led to
      the fine tuning of the bowl structures and properties. The deformation of the
      corannulene core upon functionalization has been revealed based on X-ray
      crystallographic analysis and compared for the series of cations with R=CH3 , CH2
      Cl, CHCl2 , CCl3 , CH2 CH3 , CH2 CH2 Cl, and CH2 CH2 Br. The resulting
      carbocations have been isolated with several metal-based counterions, varying in
      size and coordinating abilities ([AlCl4 ](-) , [AlBr4 ](-) , [(SnCl)(GaCl4 )2 ](
      ) , and [Al(OC(CF3 )3 )4 ](-) ). A variety of aggregation patterns in the solid
      state has been revealed based on different intermolecular interactions ranging
      from cation-anion to pi-pi stacking and to halogen???pi interactions. For the
      [C20 H10 CH2 Cl](+) ion crystallized with several different counterions, the
      conformation of the R group attached to the central five-membered ring of
      corannulene moiety was found to depend on the solid-state environment defined by
      the identity of anions. Solution NMR and UV/Vis investigations have been used to
      complement the X-ray diffraction studies for this series of corannulene-based
      cations and to demonstrate their different association patterns with the solvent
      molecules. 

PMID- 26224358
TI  - Characterising an aluminium oxide dosimetry system.
AB  - In vivo dosimetry is recommended as a defence-in-depth strategy in radiotherapy
      treatments and is currently employed by clinics around the world. The
      characteristics of a new optically stimulated luminescence dosimetry system were
      investigated for the purpose of replacing an aging thermoluminescence dosimetry
      system for in vivo dosimetry. The stability of the system was not sufficient to
      satisfy commissioning requirements and therefore it has not been released into
      clinical service at this time. 

PMID- 26224359
TI  - Which Lymph Nodes Contain Metastases in Colon Cancer Patients? A Retrospective
      Histopathological Evaluation of 156 Patients.
AB  - BACKGROUND: We hypothesized that a reliable N0 status can be established by
      sampling and evaluating the largest lymph nodes in the resected large-bowel
      specimen of patients with colon cancer. PATIENTS AND METHODS: This was a
      retrospective analysis of all surgical colon cancer patients treated between 2008
      and 2010, excluding those who had received neoadjuvant treatment. We analyzed the
      relationship between lymph node size and the presence of metastasis. Furthermore,
      we examined other prognostic factors for a histopathological N+ status. RESULTS:
      Our patient group consisted of 156 patients with a median age of 73 years (range
      = 29-91 years). A total of 2044 lymph nodes (a median of 12 per patient, range =
      2-47 nodes) were harvested, 1803 (88.2%) without and 241 (11.8%) with tumor
      spread. Using a unique ranking model, we found that in 58 out of the 59 N+
      patients (98.3%, 95% confidence interval = 90.9% to 99.9%), the largest tumor
      positive node was among the 5 largest lymph nodes in the specimen. The
      examination of >=10 lymph nodes had no effect on the chance of finding a positive
      lymph node compared with examination of <10 nodes (P = .46). CONCLUSION: In our
      study, the N-stage was determined by the 5 largest nodes in almost all specimens.
      The chance of finding a small tumor-positive node when the larger ones were clean
      was very small.

PMID- 26224360
TI  - Enhanced Neuroprotection of Minimally Invasive Surgery Joint Local Cooling Lavage
      against ICH-induced Inflammation Injury and Apoptosis in Rats.
AB  - Hypothermia treatment is one of the neuroprotective strategies that improve
      neurological outcomes effectively after brain damage. Minimally invasive surgery
      (MIS) has been an important treatment of intracerebral hemorrhage (ICH). Herein,
      we evaluated the neuroprotective effect and mechanism of MIS joint local cooling
      lavage (LCL) treatment on ICH via detecting the inflammatory responses, oxidative
      injury, and neuronal apoptosis around the hematoma cavity in rats. ICH model was
      established by type IV collagenase caudatum infusion. The rats were treated with
      MIS 6 h after injection, and then were lavaged by normothermic (37  degrees C)
      and hypothermic (33  degrees C) normal saline in brain separately. The results
      indicated that MIS joint LCL treatment showed enhanced therapeutic effects
      against ICH-induced inflammation injury and apoptosis in rats, as convinced by
      the decline of TUNEL-positive cells, followed by the decrease of IL-1beta and LDH
      and increase of IL-10 and SOD. This study demonstrated that the strategy of using
      MIS joint LCL may achieve enhanced neuroprotection against ICH-induced
      inflammation injury and apoptosis in rats with potential clinic application. 

PMID- 26224361
TI  - Transient suppression of hepatocellular replication in the mouse liver following
      transduction with recombinant adeno-associated virus.
AB  - Recombinant vectors based on adeno-associated virus (AAV) are proving to be
      powerful tools for genetic manipulation of the liver, for both discovery and
      therapeutic purposes. The system can be used to deliver transgene cassettes for
      expression or, alternatively, DNA templates for genome editing via homologous
      recombination. The replicative state of target cells is known to influence the
      efficiency of these processes and knowledge of the host-vector interactions
      involved is required for optimally effective vector deployment. Here we show, for
      the first time in vivo, that in addition to the known effects of hepatocellular
      replication on AAV-mediated gene transfer, the vector itself exerts a potent,
      albeit transient suppressive effect on cell cycle progression that is relieved on
      a time course that correlates with the known rate of clearance of input single
      stranded vector DNA. This finding requires further mechanistic investigation,
      delineates an excellent model system for such studies and further deepens our
      insight into the complexity of interactions between AAV vectors and the cell
      cycle in a clinically promising target tissue. 

PMID- 26224362
TI  - Collagen production of osteoblasts revealed by ultra-high voltage electron
      microscopy.
AB  - In the bone, collagen fibrils form a lamellar structure called the "twisted
      plywood-like model." Because of this unique structure, bone can withstand various
      mechanical stresses. However, the formation of this structure has not been
      elucidated because of the difficulty of observing the collagen fibril production
      of the osteoblasts via currently available methods. This is because the formation
      occurs in the very limited space between the osteoblast layer and bone matrix. In
      this study, we used ultra-high-voltage electron microscopy (UHVEM) to observe
      collagen fibril production three-dimensionally. UHVEM has 3-MV acceleration
      voltage and enables us to use thicker sections. We observed collagen fibrils that
      were beneath the cell membrane of osteoblasts elongated to the outside of the
      cell. We also observed that osteoblasts produced collagen fibrils with polarity.
      By using AVIZO software, we observed collagen fibrils produced by osteoblasts
      along the contour of the osteoblasts toward the bone matrix area. Immediately
      after being released from the cell, the fibrils run randomly and sparsely. But as
      they recede from the osteoblast, the fibrils began to run parallel to the
      definite direction and became thick, and we observed a periodical stripe at that
      area. Furthermore, we also observed membrane structures wrapped around
      filamentous structures inside the osteoblasts. The filamentous structures had
      densities similar to the collagen fibrils and a columnar form and diameter. Our
      results suggested that collagen fibrils run parallel and thickly, which may be
      related to the lateral movement of the osteoblasts. UHVEM is a powerful tool for
      observing collagen fibril production. 

PMID- 26224363
TI  - The association between vitamin D and parathyroid hormone and bone mineral
      density: the Dong-gu Study.
AB  - The primary objective of the present study was to investigate the relationship
      between 25-hydroxyvitamin D (25[OH]D) and areal bone mineral density (aBMD) in
      Korean subjects from the general population aged >=50 years. This study included
      8,857 individuals who completed the baseline survey of the Dong-gu study, which
      was conducted in Korea from 2007-2010. The participants who fulfilled the
      detailed inclusion criteria underwent assessment of the femoral neck and lumbar
      spine aBMD as well as measurement of serum 25(OH)D and parathyroid hormone (PTH)
      levels. After adjusting for other covariates and log-PTH values, the mean aBMD of
      the femoral neck exhibited a significant increase with increasing 25(OH)D levels
      in both males (p < 0.001) and females (p = 0.005). Additionally, the mean aBMD of
      the lumbar spine exhibited a significant increase with increasing 25(OH)D levels
      in males (p = 0.011) but not females (p = 0.252). After adjusting for covariates
      and log-25(OH)D values, the mean aBMD values of the femoral neck and lumbar spine
      showed significant decreases with increasing PTH levels in both males and females
      (p < 0.001). The present findings demonstrate that the aBMD of the femoral neck
      was significantly associated with 25(OH)D levels independent of PTH in both males
      and females and that the aBMD of the lumbar spine was significantly associated
      with 25(OH)D levels independent of PTH in males, but not females. 

PMID- 26224365
TI  - SPX proteins regulate Pi homeostasis and signaling in different subcellular
      level.
AB  - To cope with low phosphate (Pi) availability, plants have to adjust its gene
      expression profile to facilitate Pi acquisition and remobilization. Sensing the
      levels of Pi is essential for reprogramming the gene expression profile to adapt
      to the fluctuating Pi environment. AtPHR1 in Arabidopsis and OsPHR2 in rice are
      central regulators of Pi signaling, which regulates the expression of phosphate
      starvation-induced (PSI) genes by binding to the P1BS elements in the promoter of
      PSI genes. However, how the Pi level affects the central regulator to regulate
      the PSI genes have puzzled us for a decade. Recent progress in SPX proteins
      indicated that the SPX proteins play important role in regulating the activity of
      central regulator AtPHR1/OsPHR2 in a Pi dependent manner at different subcellular
      levels. 

PMID- 26224364
TI  - Severe Influenza in 33 US Hospitals, 2013-2014: Complications and Risk Factors
      for Death in 507 Patients.
AB  - BACKGROUND: Influenza A (H1N1) pdm09 became the predominant circulating strain in
      the United States during the 2013-2014 influenza season. Little is known about
      the epidemiology of severe influenza during this season. METHODS: A retrospective
      cohort study of severely ill patients with influenza infection in intensive care
      units in 33 US hospitals from September 1, 2013, through April 1, 2014, was
      conducted to determine risk factors for mortality present on intensive care unit
      admission and to describe patient characteristics, spectrum of disease,
      management, and outcomes. RESULTS: A total of 444 adults and 63 children were
      admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4
      children (6.3%) died. By logistic regression analysis, the following factors were
      significantly associated with mortality among adult patients: older age (>65
      years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9],
      P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of
      malignant tumor with chemotherapy administered within the prior 6 months (12.1
      [3.9-37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for
      each increase by 1 in score, 1.3 [1.2-1.4], P<.001). CONCLUSION: Risk factors for
      death among US patients with severe influenza during the 2013-2014 season, when
      influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in
      the first postpandemic season in which it predominated toward those of a more
      typical epidemic influenza season.

PMID- 26224366
TI  - Interplay of the PtsN (EIIA(Ntr)) protein of Pseudomonas putida with its target
      sensor kinase KdpD.
AB  - The nitrogen phosphotransferase system (PTS(Ntr) ) of Pseudomonas putida is a
      multi-component regulatory device that participates in controlling a variety of
      physiological processes in a post-translational fashion. A general survey of
      genes regulated by PtsN exposed transcription of the kdpFABC operon is most
      conspicuously affected. Measurements of kdpFp promoter activity in different pts
      mutants showed that PtsN is responsible for repression of kdpFABC transcription.
      This effect could be assigned mainly to PtsN~P, depending on the external K(+)
      concentration. Bacterial two-hybrid assays demonstrated that kdpFp regulation is
      implemented through direct interaction of the PtsN protein with the sensor kinase
      KdpD of the KdpD/KdpE two-component system. Interaction between KdpD and PtsN was
      detectable with a PtsN variant that imitates the non-phosphorylated form as well
      as with a PtsN type mimicking the phosphorylated form of PtsN. These results
      raise a regulatory scenario in which the Kdp system is regulated by the action of
      PtsN through direct interaction with the sensor kinase KdpD, and the outcome of
      such an interaction depends on the phosphorylation state of PtsN as well as on
      the external K(+) concentration. 

PMID- 26224367
TI  - Immune system changes after sexual abuse in adolescents.
AB  - BACKGROUND: The immunological changes in diseases such as rheumatoid arthritis
      and multiple sclerosis have been found to be similar to the immunological changes
      in adults with post-traumatic stress disorder (PTSD). The biological consequences
      of and immunological disruptions associated with psychological trauma in sexually
      abused adolescents were investigated in this study. METHODS: Number of peripheral
      blood cells, intracellular cytokine level and cytotoxic activity of natural
      killer cells were measured on routine blood examination samples in adolescents
      aged 13-18 referred to the outpatient unit for forensic evaluation. Forty-three
      adolescents (patients with present/lifetime PTSD [PTSD-P/PTSD-L] associated with
      a history of childhood sexual abuse, n = 33; and 10 controls) were evaluated.
      RESULTS: Eosinophil percentage was high (P < 0.05), whereas stimulated
      intracellular interferon-gamma was low (P < 0.05) in adolescents with PTSD-L
      compared with the control group. In PTSD-P patients exposed to repeated sexual
      abuse, CD3(+) HLA-DR(+) T-lymphocyte count was low (P < 0.05) compared with those
      with one-time sexual abuse. CONCLUSION: The increase in some immune system
      parameters and the decrease in several others, suggests a dysregulation of the
      immune system related to trauma in adolescents. Dysregulation of the immune
      system is known to cause autoimmune and chronic disease.

PMID- 26224369
TI  - A large-field polarisation-resolved laser scanning microscope: applications to
      CARS imaging.
AB  - Laser-scanning imaging techniques are frequently used to probe the molecule
      spatial orientation in a sample of interest by exploiting selection rules
      depending on the polarisation of the excitation light. For the successful
      implementation of these techniques the precise control of the polarisation at the
      sample level is of fundamental importance. Polarisation distortions induced by
      the optical elements are often the main limitation factor for the maximum size of
      the field-of-view in polarisation-resolved (PR) laser-scanning microscopy, since
      for large scanning angles the polarisation distortions may mask the real sample
      structure. Here we shall demonstrate the implementation of large-field-of-view PR
      microscopy and show PR CARS imaging of mouse spinal cord thanks to a careful
      design of the laser-beam optical path. We shall show that this design leads to
      strongly suppressed distortions and quantify their effects on the final images.
      Although the focus of this work is on CARS imaging, we stress that the approaches
      described here can be successfully applied to a wide range of PR laser-scanning
      techniques. 

PMID- 26224368
TI  - Calcipotriol Targets LRP6 to Inhibit Wnt Signaling in Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy in need of
      more effective treatment approaches. One potential therapeutic target is Wnt/beta
      catenin signaling, which plays important roles in PDAC tumor initiation and
      progression. Among Wnt inhibitors with suitable in vivo biologic activity is
      vitamin D, which is known to antagonize Wnt/beta-catenin signaling in colorectal
      cancer and have antitumor activity in PDAC. For this study, the relationship
      between vitamin D signaling, Wnt/beta-catenin activity, and tumor cell growth in
      PDAC was investigated through the use of calcipotriol, a potent non-hypercalcemic
      vitamin D analogue. PDAC tumor cell growth inhibition by calcipotriol was
      positively correlated with vitamin D receptor expression and Wnt/beta-catenin
      activity. Furthermore, vitamin D and Wnt signaling activity were found to be
      reciprocally linked through feedback regulation. Calcipotriol inhibited autocrine
      Wnt/beta-catenin signaling in PDAC cell lines in parallel with decreased protein
      levels of the low-density lipoprotein receptor-related protein 6 (LRP6), a
      requisite coreceptor for ligand-dependent canonical Wnt signaling. Decrease in
      LRP6 protein seen with calcipotriol was mediated through a novel mechanism
      involving transcriptional upregulation of low-density lipoprotein receptor
      adaptor protein 1 (LDLRAP1). Finally, changes in LRP6 or LDLRAP1 expression
      directly altered Wnt reporter activity, supporting their roles as regulators of
      ligand-dependent Wnt/beta-catenin signaling. IMPLICATIONS: This study provides a
      novel biochemical target through which vitamin D signaling exerts inhibitory
      effects on Wnt/beta-catenin signaling, as well as potential biomarkers for
      predicting and following tumor response to vitamin D-based therapy.

PMID- 26224370
TI  - Accuracy of Near Infrared-Guided Surgery in Morbidly Obese Subjects Undergoing
      Laparoscopic Cholecystectomy.
AB  - BACKGROUND: Fluorescence cholangiography represents an incisionless technique
      that can be applied during laparoscopic cholecystectomy to visualize bile ducts.
      Our objective was to evaluate and detect variances of fluorescence imaging in
      obese and non-obese patients. METHODS: Prospective patients were selected for
      laparoscopic cholecystectomies. Subjects were divided into groups based on their
      body mass index. Fluorescence imaging was applied preceding any dissection of
      extrahepatic ducts and again after dissection. Positive and negative
      identifications of biliary ducts were recorded. RESULTS: Seventy-one patients
      participated, with 53.5 % classified as obese. The cystic, hepatic, common bile
      duct, and accessory ducts were identified as follows: 100, 70.4, 87.3, and 7.0 %
      of patients, respectively. No differences in hepatic duct, common bile duct, and
      accessory duct visualization were detected in the obese and non-obese groups (p
      value 0.09, 0.16, and 0.66, respectively). CONCLUSIONS: Fluorescent
      cholangiography is a useful technique in the obese and non-obese population.
      Obesity does not affect fluorescence visualization of bile ducts.

PMID- 26224371
TI  - The Surgical Management of Complex Fistulas After Sleeve Gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining acceptance as the
      preferred option for treating obesity. Risks of leak and subsequent fistula after
      sleeve gastrectomy still present significant concerns in clinical practice. This
      current series presents unusual fistulas post-LSG and their surgical management.
      METHODS: The series presents chronic leaks that have progressed into fistulas.
      Three patients with fistulas are presented: gastrocolic, gastropleural, and
      gastrosplenic. Surgical intervention was warranted in all cases with en-bloc
      resection of the fistula with subtotal gastrectomy and Roux-en-Y
      esophagojejunostomy reconstruction. A subtotal colectomy with ileo-descending
      colon anastomosis was additionally necessary in the gastrocolic patient. RESULTS:
      The patients with the gastropleural and gastrosplenic fistulas were discharged
      home on postoperative Day 6 and Day 7, respectively. The patient with the
      gastrocolic fistula had an extended postoperative hospital course and was
      discharged home on postoperative Day 35. All cases were negative for staple line
      leaks. To date, the fistulas healed with no recurrence. CONCLUSIONS: En-bloc
      resection of the fistula with proximal gastrectomy and Roux-en-Y
      esophagojejunostomy (PGRYEJ) is a surgical option to treat chronic staple line
      leakage when non-operative therapy is rendered ineffective. Adequate preoperative
      planning with optimization of nutritional status and control of local and
      systemic sepsis is paramount for ultimate success. A symptomatic leak requires
      immediate operation regardless of the time interval between the primary sleeve
      operation and appearance of the leak.

PMID- 26224372
TI  - Preoperative Slow-Release Morphine Reduces Need of Postoperative Analgesics and
      Shortens Hospital Stay in Laparoscopic Gastric Bypass.
AB  - BACKGROUND: As most bariatric procedures are performed by laparoscopy, hospital
      stay is exceptionally short, despite the habitus of patients and the rather
      extensive intra-abdominal surgery. To facilitate postoperative mobilization, most
      patients are given repeated single doses of morphine, a drug with several side
      effects. We aimed to evaluate the effect of preoperative treatment with a tablet
      of slow-release morphine (SRM) on postoperative analgesic consumption and length
      of stay (LOS) in laparoscopic gastric bypass (LGBP). METHODS: The SRM group (244
      patients) was retrospectively compared to a control group (197 patients)
      concerning postoperative pain management and hospital stay by studying medical
      charts and data from Scandinavian Obesity Surgery Registry (SOReg). RESULTS:
      Patients in the SRM group needed significantly less analgesics during days 0, 1,
      and 2 postoperatively, morphine 10.7 vs. 13.6 mg, 10.2 vs. 13.9 mg, and 1.1 vs.
      3.6 mg, respectively, p < 0.05, as well as acetaminophen, p < 0.05. According to
      a subgroup analysis, 20 mg of SRM was needed to obtain these effects. In
      addition, SRM patients had shorter hospital stay (2.3 vs. 3.5 days, p < 0.05)
      than the control group. No negative side effects were seen. CONCLUSIONS:
      Preoperatively administered slow-release morphine significantly reduced the need
      for postoperative analgesics and shortened hospital stay, without side effects or
      other complications. At our department, the studied regime is now routinely used
      in all bariatric surgery and we have started to use the concept in other groups
      of surgical patients.

PMID- 26224373
TI  - Gastrobronchial Fistula in Sleeve Gastrectomy and Roux-en-Y Gastric Bypass--A
      Systematic Review.
AB  - Gastrobronchial fistula (GBF) is a rare surgical complication after bariatric
      surgery. We aimed to identify the clinical aspects of GBF and establish
      diagnostic and treatment strategies. A literature search was conducted in
      December 2013, in the PubMed electronic database. Eleven studies were selected,
      comprising a total of 36 patients. Most patients presented with a gastric leak
      prior to the diagnosis of GBF. Mean period until diagnosis was 7.2 months, and
      main presenting symptoms were productive cough (n = 13) and subphrenic abscess (n
      = 12). Endoscopic treatment was successful in 18 out of 20 patients, with minimal
      complication. Surgical treatment was successful in 17 cases with significant
      complications. GBF can be effectively treated with both endoscopic and surgical
      approach; however, surgical treatment can be associated with more complication. 

PMID- 26224374
TI  - Optimal Drug Dosing in the Obese--Still Many Years Ahead.

PMID- 26224375
TI  - What Does the Excised Stomach from Sleeve Gastrectomy Tell us?
AB  - INTRODUCTION: Staple-line leak and haemorrhage are the most serious complications
      following sleeve gastrectomy. The operation is often performed without prior
      endoscopy. Given that gastric inflammatory conditions are common, could they
      predispose patients to suffering a serious complication following sleeve
      gastrectomy? METHODS: Consecutive patients undergoing laparoscopic sleeve
      gastrectomy from March 2007 to May 2014 were included in the study. All final
      histologic reports were coded and investigated against whether or not the patient
      had a post-operative leak and/or haemorrhage. Associations were explored using
      Fisher's exact test. RESULTS: Over this period, 976 laparoscopic sleeve
      gastrectomies were performed with a pre-operative gastroscopy rate of 2.2%. Over
      half of the specimens demonstrated a histopathologic abnormality. Helicobacter
      pylori infection occurred in 8.6%, and the most common histopathologic
      abnormality was chronic gastritis in 38.9%. There was no association between H.
      pylori infection or inflammation and staple-line leak and/or haemorrhage.
      CONCLUSION: We conclude that inflammatory gastric conditions are unlikely to
      predispose patients to staple-line leaks or haemorrhages following sleeve
      gastrectomy and that selective pre-operative gastroscopy may be an appropriate
      standard of care.

PMID- 26224376
TI  - The Protective Effects of Melatonin Against Oxidative Stress and Inflammation
      Induced by Acute Cadmium Exposure in Mice Testis.
AB  - Cadmium (Cd) is widely used in daily life and was recently recognized as a
      possible source of human toxicity due to its ability to accumulate in organs.
      Previous studies have shown that Cd exposure may cause testicular toxicity
      through oxidative stress and an inflammatory effect. Melatonin has been
      demonstrated to be an effective anti-oxidant and has an anti-inflammatory effect.
      The aim of the present study was to investigate the toxicological effects of Cd
      on reproduction in male mice and the potential protective action of melatonin
      against these adverse effects. Adult male mice were injected intraperitoneally
      with Cd at a dose of 2 mg/kg body weight per day for seven consecutive days with
      or without melatonin pretreatment. Sex organ weight, sperm parameters including
      sperm quality, apoptosis, acrosome integrity, mitochondrial membrane potential,
      testicular morphology, serum sex hormone, inflammatory status, and oxidative
      stress were evaluated. The results showed that significant adverse effects were
      observed in the male reproductive system after Cd exposure, including alterations
      in sperm parameters, increased DNA damage, and sex hormone disturbance. Acute Cd
      exposure also significantly increased malondialdehyde (MDA) contents, decreased
      glutathione (GSH) and superoxide dismutase (SOD) activities, and upregulated
      levels of the pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF
      alpha), and interleukin-1beta (IL-1beta), in the testis. In contrast, melatonin
      pretreatment significantly alleviated these toxic effects, and its mechanism may
      involve inhibiting MDA level, restoring GSH and SOD activities, and reducing the
      upregulation of TNF-alpha and IL-1beta. Our data suggest that oxidative stress
      and inflammation are involved in Cd-induced toxicity in the male reproductive
      system and that co-administration of melatonin exerts a protective effect against
      Cd-induced male reproductive toxicity. 

PMID- 26224377
TI  - All-Carbon [3+3] Oxidative Annulations of 1,3-Enynes by Rhodium(III)-Catalyzed C
      H Functionalization and 1,4-Migration.
AB  - 1,3-Enynes containing allylic hydrogens cis to the alkyne function as three
      carbon components in rhodium(III)-catalyzed, all-carbon [3+3] oxidative
      annulations to produce spirodialins. The proposed mechanism of these reactions
      involves the alkenyl-to-allyl 1,4-rhodium(III) migration. 

PMID- 26224378
TI  - Carbon Nanotube-CoF2 Multifunctional Cathode for Lithium Ion Batteries: Effect of
      Electrolyte on Cycle Stability.
AB  - Transition metal fluorides (MFx ) offer remarkably high theoretical energy
      density. However, the low cycling stability, low electrical and ionic
      conductivity of metal fluorides have severely limited their applications as
      conversion-type cathode materials for lithium ion batteries. Here, a scalable and
      low-cost strategy is reported on the fabrication of multifunctional cobalt
      fluoride/carbon nanotube nonwoven fabric nanocomposite, which demonstrates a
      combination of high capacity (near-theoretical, 550mAhgCoF2-1) and excellent
      mechanical properties. Its strength and modulus of toughness exceed that of many
      aluminum alloys, cast iron, and other structural materials, fulfilling the use of
      MFx -based materials in batteries with load-bearing capabilities. In the course
      of this study, cathode dissolution in conventional electrolytes has been
      discovered as the main reason that leads to the rapid growth of the solid
      electrolyte interphase layer and attributes to rapid cell degradation. And such
      largely overlooked degradation mechanism is overcome by utilizing electrolyte
      comprising a fluorinated solvent, which forms a protective ionically conductive
      layer on the cathode and anode surfaces. With this approach, 93% capacity
      retention is achieved after 200 cycles at the current density of 100 mA g(-1) and
      over 50% after 10 000 cycles at the current density of 1000 mA g(-1) . 

PMID- 26224379
TI  - Delivery-related risk factors for covert postpartum urinary retention after
      vaginal delivery.
AB  - INTRODUCTION AND HYPOTHESIS: Postpartum urinary retention (PUR) is a common
      consequence of bladder dysfunction after vaginal delivery. Patients with covert
      PUR are able to void spontaneously but have a postvoid residual bladder volume
      (PVRV) of >=150 mL. Incomplete bladder emptying may predispose to bladder
      dysfunction at a later stage of life. The aim of this cross-sectional study was
      to identify independent delivery-related risk factors for covert PUR after
      vaginal delivery in order to identify women with an increased risk of covert PUR.
      METHODS: The PVRV of women who delivered vaginally was measured after the first
      spontaneous micturition with a portable bladder-scanning device. A PVRV of 150 mL
      or more was defined as covert PUR. Independent risk factors for covert PUR were
      identified in multivariate regression analysis. RESULTS: Of 745 included women,
      347 (47%) were diagnosed with covert PUR (PVRV >=150 mL), of whom 197 (26%) had a
      PVRV >=250 mL (75th percentile) and 50 (7%) a PVRV >=500 mL (95th percentile). In
      multivariate regression analysis, episiotomy (OR 1.7, 95% CI 1.02 - 2.71),
      epidural analgesia (OR 2.08, 95% CI 1.36 - 3.19) and birth weight (OR 1.03, 95%
      CI 1.01 - 1.06) were independent risk factors for covert PUR. Opioid analgesia
      during labour (OR 3.19, 95% CI 1.46 - 6.98), epidural analgesia (OR 3.54, 95% CI
      1.64 - 7.64) and episiotomy (OR 3.72, 95% CI 1.71 - 8.08) were risk factors for
      PVRV >=500 mL. CONCLUSIONS: Episiotomy, epidural analgesia and birth weight are
      risk factors for covert PUR. We suggest that the current cut-off values for
      covert PUR should be reevaluated when data on the clinical consequences of
      abnormal PVRV become available.

PMID- 26224380
TI  - Female paraurethral leiomyoma: treatment and long-term follow-up.
AB  - INTRODUCTION: We describe our experience with evaluating the ideal management of
      female paraurethral leiomyomas from imaging to surgery and follow-up. METHODS:
      Between January 2009 and January 2012, we treated six women (age range 32-49
      years) affected by paraurethral leiomyoma of different sizes. RESULTS: All the
      six patients underwent transvaginal excision of the mass. They are free of
      recurrence at follow-up (range 32-72 months). Two patients developed stress
      urinary incontinence after the excision: in both cases, incontinence was
      corrected by a tension-free vaginal tape-obturator (TVT-O) placement. In one
      patient, a fascial sling was necessary to repair a urethral lesion that developed
      during surgical excision of the mass. CONCLUSION: A well-defined protocol for
      diagnosing and managing a paraurethral mass had not been established as yet due
      the rarity of the mass. We suggest performing pelvic magnetic resonance imaging
      (MRI) as a primary examination, followed by lesion biopsy. Complete surgical
      resection performed transvaginally should be the treatment of choice. As
      paraurethral leiomyomas does not originate from intraurethral smooth-muscle
      component, urethral lesion is rare. Excision of female urethral leiomyoma
      transvaginally is safe, and postoperative urinary incontinence, if any, can be
      easily corrected with minimally invasive tecniques.

PMID- 26224381
TI  - Risk factors for severe obstetric perineal lacerations.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the occurrence
      of severe perineal lacerations in vaginal delivery and its relationship with
      predisposing clinical and obstetric factors. METHODS: A retrospective cohort
      analysis using an electronic clinical database at a University Referral Center
      for high-risk pregnancies was performed. A total of 941 vaginal deliveries were
      analyzed, over 10 consecutive months in 2013 and 2014. The relationship between
      obstetric and clinical characteristics and lacerations, especially severe forms,
      was analyzed. The frequency and severity of birth canal lacerations were compiled
      and classified as mild (unintentional laceration grades I and II, and
      mediolateral episiotomy) and severe (grades III and IV). The crude and adjusted
      odds ratios and 95% confidence intervals were estimated in univariate and
      multivariate logistic regression models. RESULTS: The overall incidence of
      perineal lacerations in vaginal delivery was 78.2% (n = 731). Lacerations were
      considered mild in 708 women (75.7%) and severe in 23 women (2.5%). Maternal age,
      parity, use of forceps, mediolateral episiotomy, and birth weight influenced the
      occurrence of some degree of tear. The chance of severe lacerations increased
      1.77-fold per week with the gestational age (1.03-3.03, P = 0.025), while
      primiparity increased the chance of laceration 5.32-fold. Episiotomy did not show
      a protective effect against severe laceration occurrence (P = 0.999).
      CONCLUSIONS: Severe perineal lacerations were associated with operative delivery,
      primiparity, gestational age, and epidural anesthesia. Episiotomy was not
      protective.

PMID- 26224382
TI  - Cannabinoid receptor expression in the bladder is altered in detrusor
      overactivity.
AB  - INTRODUCTION: Immunohistochemical (IHC) evidence shows that cannabinoid receptors
      (CB) are expressed in human bladders and cannabinoid agonists are known to
      inhibit detrusor contractility. However, the mechanism for this inhibition
      remains unknown. In addition, the role of CB in detrusor overactivity (DO) is
      under-investigated. The aim of this study was to compare CB expression in normal
      and DO human bladders and to further characterise these receptors. METHODS:
      Polymer chain reaction (PCR) was used to detect differences in CB transcripts in
      bladder samples. Differences in CB protein expression was assessed by IHC.
      Immunofluorescence (IF) was used to evaluate co-localisation of CB with nerve
      fibres. Receptor density and binding affinity were measured using the cannabinoid
      radioligand [(3)H]-CP-55,940. RESULTS: There were higher levels of CB1
      transcripts in the urothelium of patients with DO and lower levels in the
      detrusor, compared with normal bladders. Radioligand binding revealed CB density
      of 421 +/- 104 fmol/mg protein in normal human bladders. IHC confirmed these
      findings at the protein level. IF staining demonstrated co-localisation of CB1
      with choline acetyltransferase-(ChAT)-positive nerves in the detrusor and co
      localisation with PGP9.5 in both urothelium and detrusor. CB2 was co-localised
      with both ChAT and PGP9.5 in the urothelium and the detrusor. CONCLUSIONS:
      Cannabinoid receptor expression is reduced in the detrusor of patients with DO,
      which may play a role in the pathophysiology of the disease. Co-localisation of
      CB receptors with cholinergic nerves may suggest that CB1, being localised on pre
      and postsynaptic terminals, could influence neurotransmitter release. Our
      findings suggest the potential role of cannabinoid agonists in overactive bladder
      pharmacotherapy.

PMID- 26224384
TI  - Are current archiving systems reliable enough?

PMID- 26224383
TI  - Assessment of urethral support using MRI-derived computational modeling of the
      female pelvis.
AB  - INTRODUCTION AND HYPOTHESIS: This study aimed to assess the role of individual
      anatomical structures and their combinations to urethral support function.
      METHODS: A realistic pelvic model was developed from an asymptomatic female
      patient's magnetic resonance (MR) images for dynamic biomechanical analysis using
      the finite element method. Validation was performed by comparing simulation
      results with dynamic MR imaging observations. Weaknesses of anatomical support
      structures were simulated by reducing their material stiffness. Urethral mobility
      was quantified by examining urethral axis excursion from rest to the final state
      (intra-abdominal pressure = 100 cmH2O). Seven individual support structures and
      five of their combinations were studied. RESULT: Among seven urethral support
      structures, we found that weakening the vaginal walls, puborectalis muscle, and
      pubococcygeus muscle generated the top three largest urethral excursion angles. A
      linear relationship was found between urethral axis excursions and intra
      abdominal pressure. Weakening all three levator ani components together caused a
      larger weakening effect than the sum of each individually weakened component,
      indicating a nonlinearly additive pattern. The pelvic floor responded to
      different weakening conditions distinctly: weakening the vaginal wall developed
      urethral mobility through the collapsed vaginal canal, while weakening the
      levator ani showed a more uniform pelvic floor deformation. CONCLUSIONS: The
      computational modeling and dynamic biomechanical analysis provides a powerful
      tool to better understand the dynamics of the female pelvis under pressure
      events. The vaginal walls, puborectalis, and pubococcygeus are the most important
      individual structures in providing urethral support. The levator ani muscle group
      provides urethral support in a well-coordinated way with a nonlinearly additive
      pattern.

PMID- 26224385
TI  - Topographical relationships between the obturator nerve, artery, and vein in the
      lateral pelvic wall.
AB  - INTRODUCTION AND HYPOTHESIS: The aims of this study were to determine the
      topographical relationships between the obturator nerve (ON), artery (OA), and
      vein (OV) in the lateral pelvic wall. METHODS: One hundred and fifty hemipelvises
      of 84 Korean cadavers were dissected. RESULTS: The ON, OA, and OV ran in that
      order (from upper to lower) within the lateral pelvic wall in 46.7 % of
      specimens. In 32 % of cases, the three structures were separated at the posterior
      portion of the wall and then converged toward the obturator canal (OC). In 10 %,
      the OA and OV were in contact with each other and separate from the ON; in 2 %,
      the ON was contiguous with the OA and separate from the OV; in 2.7 %, all three
      structures were in contact with each another. Alternately, the order of ON, OA,
      and OV was altered in the lateral pelvic wall in 41.3 % of specimens. Finally, in
      12 % specimens, either the OA or OV or both were absent from the lateral pelvic
      wall. CONCLUSIONS: The possibility of the presence of either the OA or OV being
      between the ON and the external iliac vein, and the potential contact between the
      ON and either the OA or OV in the lateral pelvic wall, should be borne in mind
      during pelvic procedures.

PMID- 26224386
TI  - Out of the blue: adaptive visual pigment evolution accompanies Amazon invasion.
AB  - Incursions of marine water into South America during the Miocene prompted
      colonization of freshwater habitats by ancestrally marine species and present a
      unique opportunity to study the molecular evolution of adaptations to varying
      environments. Freshwater and marine environments are distinct in both spectra and
      average intensities of available light. Here, we investigate the molecular
      evolution of rhodopsin, the photosensitive pigment in the eye that activates in
      response to light, in a clade of South American freshwater anchovies derived from
      a marine ancestral lineage. Using likelihood-based comparative sequence analyses,
      we found evidence for positive selection in the rhodopsin of freshwater anchovy
      lineages at sites known to be important for aspects of rhodopsin function such as
      spectral tuning. No evidence was found for positive selection in marine lineages,
      nor in three other genes not involved in vision. Our results suggest that an
      increased rate of rhodopsin evolution was driven by diversification into
      freshwater habitats, thereby constituting a rare example of molecular evolution
      mirroring large-scale palaeogeographic events. 

PMID- 26224387
TI  - Grazer-induced morphological defense in Scenedesmus obliquus is affected by
      competition against Microcystis aeruginosa.
AB  - The green alga Scenedesmus is known for its phenotypic plasticity in response to
      grazing risk. However, the benefits of colony formation induced by infochemicals
      from zooplankton should come with costs. That is, a tradeoff in benefit-to-cost
      ratios is likely under complex environmental conditions. In this study, we
      hypothesized that the coexistence of Scenedesmus and its competitors decreases
      the formation of anti-grazer colonies in Scenedesmus. Results demonstrated that
      the presence of a competitor Microcystis aeruginosa inhibited inducible defensive
      colony formation of Scenedesmus obliquus, and the established defensive colonies
      negatively affected the competitive ability of S. obliquus. The proportion of
      induced defensive colonies in cultures was dependent on the relative abundance of
      competitors. Under low competition intensity, large amount of eight-celled
      colonies were formed but at the cost of decreased competitive inhibition on M.
      aeruginosa. By contrast, defensive colony formation of S. obliquus slacked in the
      presence of high competition intensity to maintain a high displacement rate
      (competitive ability). In conclusion, S. obliquus exhibited different responses
      to potential grazing pressure under different intensities of competition, i.e.,
      Scenedesmus morphological response to grazing infochemicals was affected by
      competition against Microcystis. 

PMID- 26224389
TI  - Maternal adaptation to pregnancy is at least in part influenced by fetal gender.

PMID- 26224388
TI  - Volatile organic compounds in truffle (Tuber magnatum Pico): comparison of
      samples from different regions of Italy and from different seasons.
AB  - In this paper volatile organic compounds (VOCs) from Tuber magnatum fruiting
      bodies were analyzed using a PTR-TOF-MS instrument. The aim was to characterize
      the VOC's profile of the fruiting bodies and identify if any VOCs were specific
      to a season and geographical areas. Multiple factorial analysis (MFA) was carried
      out on the signals obtained by MS. Experiments using ITS region sequencing proved
      that the T. magnatum life cycle includes the formation of fruiting bodies at two
      different times of the year. The VOCs profiles diverge when different seasonal
      and geographical productions are considered. Using PTR-TOF-MS, compounds present
      at levels as low pptv were detected. This made it possible to determine both the
      origin of fruiting bodies (Alba and San Miniato) and the two biological phases of
      fruiting bodies formation in San Miniato truffles.

PMID- 26224390
TI  - Stenting and Adjunctive Delivery of Paclitaxel Via Balloon Coating Versus Durable
      Polymeric Matrix for De Novo Coronary Lesions: Clinical and Angiographic Results
      from the Prospective Randomized Trial.
AB  - BACKGROUND: There is limited comparative clinical data regarding the safety and
      efficacy profile of paclitaxel delivery via balloon versus stent-polymer matrix.
      In this study, we aimed to compare the clinical and angiographic results of two
      different methods of paclitaxel delivery among patients undergoing percutaneous
      coronary intervention (PCI) for single de novo coronary lesions. METHODS: A total
      of 202 patients undergoing PCI due to symptomatic heart disease and at least one
      significant coronary artery lesion were prospectively enrolled in a multicenter
      non-inferiority trial. Eligible patients were randomized to a revascularization
      with either a paclitaxel eluting stent (PES = Coroflex Please, B.Braun) or a bare
      metal stent (BMS) followed by a paclitaxel coated balloon (PCB) dilation (BMS =
      Coroflex + PCB = Sequent Please, B.Braun). Clinical follow-up was obtained at 9
      months in all patients, whereas angiographic in a subset of 94 (46.5%) patients.
      RESULTS: The baseline characteristics were well balanced between groups. At 9
      months, the primary endpoint of in-stent late lumen loss in BMS + PCB was
      comparable and non-inferior to PES (0.21 +/- 0.5 vs. 0.30 +/- 0.7 mm,
      respectively. P(non-inf)  < 0.05). At 9 months, the incidence of MACE (7.0 vs.
      6.9%, HR = 1, 95%CI: 0.3-2.8; P = 0.99), comprising the occurrence of myocardial
      infarction (4.9 vs. 3.0%, HR = 1.62, 95%CI: 0.4-6.5; P = 0.32), target lesion
      revascularization (6.9 vs. 5.0%, HR = 1.42, 95%CI: 0.4-4.4; p = 0.54) and stent
      thrombosis (4.9 vs. 3.0%, HR = 2.01, 95%CI: 0.5-7.4; P = 0.74) was comparable
      between BMS + PCB and PES, respectively. In the BMS + PCB group, thrombosis
      tended to occur within 30 days (3.9 vs. 1.0%; P = 0.38). CONCLUSIONS: Paclitaxel
      delivery via drug coated balloon or polymer-stent matrix achieved comparable
      angiographic and clinical results among patients with de novo coronary lesions.
      BMS + PCB revascularization was associated with a higher rate of stent thrombosis
      when compared to newer generation drug eluting stents, therefore, should be
      recommended as a bail-out for PCB alone angioplasty.

PMID- 26224391
TI  - Effectiveness of Biodegradable Magnesium Alloy Stents in Coronary Artery and
      Femoral Artery.
AB  - OBJECTIVES: To access the biocompatibility, effectiveness, and safety of
      biodegradable magnesium (Mg) alloy stent (BMAS) in the coronary artery and
      femoral artery. BACKGROUND: Atherosclerosis is a lesion of cardiovascular system,
      including the diseases in heart and blood vessels. METHODS: The aluminum (Al) and
      zinc (Zn)-based BMAS was designed by cold drawing methods. Forty healthy
      immunized mongrel dogs were randomly divided into 8 groups. Five dogs who have
      not been treated with stent were included in control group. The other dogs were
      implanted with an absorbable magnesium (Mg) alloy in the coronary and/or femoral
      artery, and their artery angiography were observed at 7 time points (1, 3, 5, 7,
      14, 21, and 28 days; n = 5) follow-up. Dogs from each cohort were sacrificed
      following angiography for pathology assessment. The histological response
      including inflammatory response, thrombosis, and intimal hyperplasia were
      analyzed by hematoxylin-eosin staining. Lumen area (La), intimal hyperplasia area
      (IHa), and the ratio of IHa were calculated by image analysis software. RESULTS:
      The thin-walled BMAS were designed and produced by cold-drawing technology. Fifty
      one devices were implanted into coronary artery of 35 dogs successfully. During
      the follow-up days, the angiography of coronary artery and femoral artery had
      confirmed that the lumen was clear and there were no elastic recoil and
      thrombosis. The stents were completely disappeared at 7 days after implantation.
      Moderate intimal hyperplasia was found at 14 days after implantation. CONCLUSION:
      The BMAS stent proved to be of good biocompatibility, safety, and effectiveness.
      (J Interven Cardiol 2015;XXXX:XX-XX).

PMID- 26224392
TI  - Feasibility and Efficacy of Herculink Elite ((TM)) Biliary Stent Implantation in
      Large Coronary Arteries (>= 5 mm) and Venous Conduits: An Observational Study.
AB  - BACKGROUND AND OBJECTIVES: Percutaneous coronary intervention (PCI) in patients
      with lesions of large calibre coronary arteries (>= 5 mm) and saphenous venous
      grafts (>= 5 mm) can be challenging. There are no separate guidelines available
      to treat these vessels with PCI. Standard coronary stents of 4 mm diameter are
      used to treat these lesions conventionally but carry the risk of under
      deployment, distortion of stent architecture and future stent thrombosis even if
      they are subsequently expanded beyond 5 mm. METHODS AND RESULTS: Biliary stents
      (Herculink EliteTM) provide a better alternative to standard coronary stents in
      these patients. These stents are of larger diameter (5-7 mm) and can be safely
      delivered over a 6 French sheath. In our case series, we demonstrate the use of
      intravascular ultrasound examination to confirm that biliary stents provide
      improved stent strut apposition within the coronary artery associated with
      extremely low repeat revascularisation rates. CONCLUSION: Our paper highlights
      that PCI of lesions in patients with large calibre coronary arteries can
      successfully be achieved using biliary stents.

PMID- 26224393
TI  - Evolving Techniques to Improve Radial/Ulnar Artery Access: Crossover Rate of 0.3%
      in 1,000 Consecutive Patients Undergoing Cardiac Catheterization and/or
      Percutaneous Coronary Intervention via the Wrist.
AB  - OBJECTIVES: To evaluate several techniques to reduce crossover rates in wrist
      artery access in patients undergoing cardiac catheterization (CC)/percutaneous
      coronary intervention (PCI). BACKGROUND: Palpation-guided radial artery (RA)
      access for CC/PCI is associated with a crossover rate to femoral artery (FA)
      access in up to 7.6%. METHODS: A retrospective analysis of a single-center
      consecutive series of patients undergoing CC/PCI was performed. After one 0.4 mg
      sublingual NTG tablet, the RA and UA were assessed by intraprocedural ultrasound
      imaging to select the more suitable artery for ultrasound-guided access. A tight
      "knuckle wire" technique using a 0.014 inch Prowater(r) coronary wire was used to
      negotiate RA, UA, and brachial loops when a standard wire would not easily cross.
      Crossover was defined as any reason requiring secondary arterial access from the
      contralateral arm or FA. RESULTS: A total of 1,162 consecutive patients treated
      from January 2012 to April 2014 were evaluated. Primary arterial access from the
      wrist (RA/UA) was performed in 1,000 (86.1%, RA: 977, UA 23) and planned FA
      access in 162 patients (13.9%). The overall crossover rate from the wrist was
      0.3% as a result of 3/1,000 patients requiring crossover to the contralateral arm
      (radial loop: n = 1, brachial loop: n = 1, vessel injury: n = 1). No crossover to
      the FA was necessary. All primary FA access sites were successful. CONCLUSIONS:
      Crossover rates of primary wrist artery access to alternative arterial access for
      CC/PCI can be reduced to less than 1% applying the aforementioned techniques.

PMID- 26224394
TI  - Letter to the Editor: "CABG after STEMI"--Is Anytime the Right Time?

PMID- 26224395
TI  - Paper diagnostic device for quantitative electrochemical detection of ricin at
      picomolar levels.
AB  - We report a paper-based assay platform for detection of ricin a chain. The paper
      platform is assembled by simple origami paper folding. The sensor is based on
      quantitative, electrochemical detection of silver nanoparticle labels linked to a
      magnetic microbead support via a ricin immunosandwich. Importantly, ricin was
      detected at concentrations as low as 34 pM. Additionally, the assay is robust,
      even in the presence of 100-fold excess hoax materials. Finally, the device is
      easily remediated after use by incineration. The cost of the device, not
      including reagents, is just $0.30. The total assay time, including formation of
      the immunosandwich, is 9.5 min. 

PMID- 26224396
TI  - In Vitro Assessment of Uptake and Lysosomal Sequestration of Respiratory Drugs in
      Alveolar Macrophage Cell Line NR8383.
AB  - PURPOSE: To assess accumulation and lysosomal sequestration of 9 drugs used in
      respiratory indications (plus imipramine as positive control) in the alveolar
      macrophage (AM) cell line NR8383. METHODS: For all drugs, uptake at 5 MUM was
      investigated at 37 and 4 degrees C to delineate active uptake and passive
      diffusion processes. Accumulation of basic clarithromycin, formoterol and
      imipramine was also assessed over 0.1-100 MUM concentration range. Lysosomal
      sequestration was investigated using ammonium chloride (NH4Cl), monensin and
      nigericin. Impact of lysosomal sequestration on clarithromycin accumulation
      kinetics was investigated. RESULTS: Both cell-to-medium concentration ratio (Kp)
      and uptake clearance (CLuptake) ranged > 400-fold for the drugs investigated. The
      greatest Kp was observed for imipramine (391) and clarithromycin (82), in
      contrast to no accumulation seen for terbutaline. A concentration-dependent
      accumulation was evident for the basic drugs investigated. Imipramine and
      clarithromycin Kp and CLuptake were reduced by 59-85% in the presence of NH4Cl
      and monensin/nigericin, indicating lysosomal accumulation, whereas lysosomal
      sequestration was not pronounced for the other 8 respiratory drugs.
      Clarithromycin uptake rate was altered by NH4Cl, highlighting the impact of
      subcellular distribution on accumulation kinetics. CONCLUSIONS: This study
      provides novel evidence of the utility of NR8383 for investigating accumulation
      and lysosomal sequestration of respiratory drugs in AMs.

PMID- 26224397
TI  - Wilms tumor gene single nucleotide polymorphism rs16754 predicts a favorable
      outcome in children with acute lymphoblastic leukemia.
AB  - PURPOSE: Wilms tumor gene single nucleotide polymorphism (WT1 SNP) rs16754 has
      been described as a favorable risk marker in patients with acute myeloid
      leukemia. Subsequent studies revealed inconsistent results in both adult and
      pediatric patients. We analyzed its impact on clinical outcome in children with
      acute lymphoblastic leukemia (ALL) for the first time. METHODS: WT1 SNP rs16754
      of 158 children with ALL treated according to ALL Berlin-Frankfurt-Munster
      treatment trials from 1990 to 2009 and 43 hematopoietic stem cell donors was
      analyzed by allelic discrimination. WT1 SNP status was correlated with disease
      characteristics and clinical outcome comparing SNP (WT1(GG/AG)) and wildtype
      (WT1(AA)). RESULTS: At least one minor allele was found in 23.4 % of patients and
      34.9 % of donors (P = 0.07). Distribution of patient and disease characteristics
      was similar between WT1(GG/AG) and WT1(AA). In multivariate analyses, WT1 SNP was
      an independent good prognostic marker for cumulative incidence of relapse (CIR
      WT1(AA) vs. WT1(GG/AG) HR = 3.384, P = 0.021) and event-free survival (EFS; event
      risk WT1(AA) vs. WT1(GG/AG) HR = 2.503, P = 0.036). Univariate subanalyses of
      patients who underwent an allogeneic hematopoietic stem cell transplantation
      revealed more significant differences in CIR (P = 0.017), EFS (P = 0.012), and
      overall survival (OS; P = 0.017). Donor's WT1 SNP status did not affect outcome.
      We found no correlation between WT1 SNP and WT1 expression level at diagnosis (P
      = 0.634). CONCLUSION: WT1 SNP rs16754 predicts improved CIR and EFS. Outcome
      differences were more prominent in transplanted children. Our findings identify
      WT1 SNP rs16754 as a favorable risk marker in pediatric ALL which is independent
      from known risk factors.

PMID- 26224399
TI  - Understanding the association between developing a fatty liver and subsequent
      cardio-metabolic complications.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic
      liver disease in Western countries and is also predicted to become the most
      frequent indication for liver transplantation by 2030. In the last decade, it has
      become evident that the clinical burden of NAFLD is not restricted to liver
      related morbidity or mortality, but there is now compelling evidence that NAFLD
      is a multisystem disease, affecting many extra-hepatic organs. In this article,
      we discuss the evidence linking NAFLD with important cardiometabolic
      complications (mainly Type 2 diabetes and cardiovascular disease) and the
      putative underlying mechanisms by which NAFLD may contribute to the development
      of these complications. 

PMID- 26224400
TI  - Metabolic Syndrome and Cardiovascular Risk in Elderly Treated Hypertensive
      Patients.
AB  - BACKGROUND: The independent prognostic significance of the metabolic syndrome
      (MetS) in the elderly is not yet clear. We investigated the association between
      MetS and cardiovascular risk (composite endpoint of stroke and coronary events)
      in elderly treated hypertensive patients. METHODS: Cardiovascular outcome was
      evaluated in 1,191 elderly treated hypertensive patients (>=60 years). Among
      them, 578 (48.5%) had MetS according to a modified joint interim statement
      definition (body mass index in place of waist circumference). RESULTS: During the
      follow-up (9.1+/-4.9 years, range 0.4-20 years), 139 strokes and 120 coronary
      events occurred. In univariate analysis, patients with MetS had higher risk of
      the composite endpoint (hazard ratio (HR) 1.322, 95% confidence interval (CI)
      1.035-1.688, P < 0.05). Among the single components of MetS, only blood pressure
      (BP) level and impaired fasting glucose/diabetes were significantly associated
      with increased cardiovascular risk. After adjustment for age, previous events,
      estimated glomerular filtration rate (eGFR), left ventricular (LV) hypertrophy
      and left atrial (LA) enlargement, the prognostic relevance of MetS was attenuated
      (HR 1.245, 95% CI 0.974-1.591, P = 0.08). After further adjustment for the above
      mentioned variables and ambulatory BP parameters and impaired fasting
      glucose/diabetes, Cox regression analysis showed that MetS was not independently
      associated with increased cardiovascular risk (HR 1.090, 95% CI 0.805-1.475, P =
      0.58). CONCLUSIONS: In elderly treated hypertensive patients, MetS is associated
      with increased cardiovascular risk, but not independently of BP and glucose
      levels and of organ damage.

PMID- 26224402
TI  - Evaluation of Adjuvant Radiation Therapy for Resected Gallbladder Carcinoma: A
      Multi-institutional Experience.
AB  - PURPOSE: The role of adjuvant radiation for gallbladder carcinoma (GBC) is
      uncertain. We combine the experience of six National Cancer Institute-designated
      cancer centers to explore the impact of adjuvant radiation following oncologic
      resection of GBC. METHODS: Patients who underwent extended surgery for GBC at
      Johns Hopkins, Mayo Clinic, Duke University, Oregon Health & Science University,
      University of Michigan, and University of Texas MD Anderson between 1985 and 2008
      were reviewed. Patients with metastatic disease at surgery, gross residual
      disease, or missing pathologic information were excluded. RESULTS: Of the 112
      patients identified, 61 % received adjuvant radiation, 93 % of whom received
      concurrent chemotherapy. Median follow-up of surviving patients was 47.3 (range
      2.2-167.7) months. Patients who received adjuvant radiation had a higher rate of
      advanced T-stage (57 vs. 16 %, p < 0.01), lymph node involvement (63 vs. 18 %, p
      < 0.01), and positive microscopic margins (37 vs. 9 %, p < 0.01) compared with
      patients managed with surgery alone, but overall survival (OS) was comparable
      between the two cohorts (5-year OS: 49.7 vs. 52.5 %, p = 0.20). Lymph node
      involvement had the strongest association with poor OS (p < 0.01). Adjuvant
      radiation was associated with decreased isolated local failure (hazard ratio
      0.17, 95 % confidence interval 0.05-0.63, p = 0.01). However, 71 % of recurrences
      included distant failure. CONCLUSIONS: Following oncologic resection for GBC,
      adjuvant radiation may offer improved local control compared with observation.
      The benefit of adjuvant radiation beyond chemotherapy alone should therefore be
      explored. Certainly, the high rate of distant failure highlights the need for
      more effective systemic therapy.

PMID- 26224403
TI  - Melanoma: Advances in Targeted Therapy and Molecular Markers.
AB  - PURPOSE AND DESIGN: In recent years, there have been dramatic improvements in the
      diagnosis and treatment of patients with melanoma. The development of molecular
      markers and associated targeted therapies have given new hope to subsets of
      patients with advanced disease. Here we discuss the most important advances in
      molecular targeted therapy and how these developments are likely to affect the
      practice of the clinical surgeon. RESULTS AND CONCLUSIONS: Germ-line and somatic
      mutations are common in melanoma and provide prognostic information that can now
      be harnessed to provide a more personalized approach to cancer treatment. BRAF
      mutation at the V600 position is the most commonly identified mutation in
      patients with melanoma. Treatment with targeted inhibitors in patients with BRAF
      mutant melanoma has afforded dramatic responses in about half of selected
      patients. Unfortunately, disease control is not durable and recurrences are
      common. We predict an increasing role for the surgeon in the multidisciplinary
      treatment of patients with metastatic disease, as well as a role for molecular
      profiling in patients with high-risk early stage disease. Further, we are only
      beginning to understand the prognostic significance of various gene mutations in
      patients with melanoma.

PMID- 26224401
TI  - Associations Between Genetic Variants of the Natriuretic Peptide System and Blood
      Pressure Response to Dietary Sodium Intervention: The GenSalt Study.
AB  - BACKGROUND: The aim of this study was to comprehensively test the association of
      genetic variants in the natriuretic peptide (NP) system with blood pressure (BP)
      response to dietary sodium intervention in a Chinese population. METHODS: We
      conducted a 7-day low-sodium intervention followed by a 7-day high-sodium
      intervention among 1,906 participants in rural China. BP measurements were
      obtained at baseline and each dietary intervention using a random-zero
      sphygmomanometer. Linear mixed-effect models were used to assess the associations
      of 48 single-nucleotide polymorphisms (SNPs) in 6 genes of NP system with BP
      response to dietary sodium intervention. RESULTS: SNP rs5063 in the NPPA gene and
      SNP rs2077386 in the NPPC gene exhibited significant associations with BP
      response to low-sodium dietary intervention under recessive genetic model. For
      rs5063, absolute mean arterial pressure responses (95% confidence interval) to
      the low-sodium intervention were 1.31 (-1.08, 3.70) mm Hg for TT genotype and 
      3.74 (-4.01, -3.46) mm Hg for CC or TC genotype, respectively (P = 4.1 * 10(-5)).
      Individuals with at least one copy of the C allele of rs2077386 had significantly
      reduction in systolic BP during the low-sodium intervention compared to those
      with genotype GG with responses of -5.48 (-5.83, -5.14) vs. -2.76 (-3.52, -2.00)
      mm Hg, respectively (P = 1.9 * 10(-13)). CONCLUSIONS: These novel findings
      suggested that genetic variants of NP system may contribute to the variation of
      BP response to sodium intervention in Chinese population. Certainly, replication
      of these results in other populations and further functional studies are
      warranted to clarify their role in the regulation of BP and hypertension.

PMID- 26224404
TI  - Normal Axillary Ultrasound Excludes Heavy Nodal Disease Burden in Patients with
      Breast Cancer.
AB  - BACKGROUND: Axillary lymph node stage is important in guiding adjuvant treatment
      for breast cancer. The role of axillary ultrasound (AUS) in axillary staging is
      uncertain. METHODS: From an institutional database, all newly diagnosed invasive
      breast carcinomas from February 1, 2011 to October 31, 2014 were identified;
      exclusions were for stage IV disease, palpable adenopathy, or receipt of
      neoadjuvant chemotherapy. AUS findings, categorized as suspicious versus not
      suspicious, were correlated with the number of nodal metastasis from surgical
      pathology. The false-negative rate of nonsuspicious AUS for identifying >=3 lymph
      nodes positive on final pathology was calculated. RESULTS: A total of 513 cancers
      were included. Overall, 400 AUSs were not suspicious (78%), and 113 were
      suspicious (22%). The sensitivity and specificity of AUS for predicting >=3 nodal
      metastasis were 71 and 83%, respectively. The false-negative rate for detecting
      >=3 nodal metastasis was 4%. False-negative rate was higher for lobular versus
      nonlobular carcinomas (12.0 vs. 2.3%, p = 0.004) and for pT2-pT4 tumors versus
      pT1 tumors (8.2 vs. 1.7 %, p = 0.005). CONCLUSIONS: Patients with normal axillary
      physical exam and ultrasound rarely harbor a large nodal disease burden.
      Randomized trials of sentinel lymph node biopsy versus no axillary surgery in
      patients with normal AUS must be powered for subgroup analysis of patients with
      invasive lobular carcinoma and pT2-pT4 tumors. Preoperative identification of
      nodal metastasis may decrease the need for second surgeries and identify
      candidates for neoadjuvant chemotherapy. AUS is a noninvasive means of predicting
      disease burden preoperatively and as such is a powerful tool to individualize
      treatment plans.

PMID- 26224405
TI  - Predictors of Residual Tumor in Breast-Conserving Therapy.
AB  - BACKGROUND: Breast-conserving therapy is considered to be the standard treatment
      for early breast tumors (T1-T2). In up to 82 % of breast-conserving surgery,
      tumor cells were still found to be present at or near the cut edge of the
      surgical specimen after surgery. Thus, it is of clinical need to identify tumors
      at high probability for reexcision in the preoperative setting. METHODS: A total
      of 686 patients with invasive or in situ breast cancers and primary breast
      conserving surgery were included. In 169 cases (24.6 %), breast-conserving
      therapy was either incomplete or the presence of residual tumor could not be
      assessed. By univariate analysis, the following parameters were associated with
      increased probability for reexcision: carcinoma in situ component next to the
      invasive tumor (p < 0.001), lower age (p = 0.025), premenopausal status (p =
      0.033), tumor size (p < 0.001), multifocality (p < 0.001), involved lymph nodes
      (p = 0.006) and lymphovascular invasion (p < 0.001), differentiation (p = 0.002),
      and overexpression of the Her2/neu receptor (p = 0.004). The variables with the
      strongest impact on the reexcision probability in multivariate analyses were
      tumor size and histology (both p < 0.001), followed by multifocality (p = 0.002)
      and an accompanying carcinoma in situ (p = 0.004). Lymphovascular invasion (p =
      0.016) and age (p = 0.047) also were significantly associated with increased
      reexcision probability in multivariate analyses. A nomogram for predicting
      residual tumor in breast-conserving therapy was developed. CONCLUSIONS: The
      clinical and pathological parameters associated with increased reexcision rates
      will help to assess an optimized surgical margin, to decrease reexcision rates,
      and therefore to improve patient care and the quality of life for patients.

PMID- 26224406
TI  - Performance and Practice Guideline for the Use of Neoadjuvant Systemic Therapy in
      the Management of Breast Cancer.
AB  - PURPOSE: The American Society of Breast Surgeons (ASBrS) sought to provide an
      evidence-based guideline on the use of neoadjuvant systemic therapy (NST) in the
      management of clinical stage II and III invasive breast cancer. METHODS: A
      comprehensive nonsystematic review was performed of selected peer-reviewed
      literature published since 2000. The Education Committee of the ASBrS convened to
      develop guideline recommendations. RESULTS: A performance and practice guideline
      was prepared to outline the baseline assessment and perioperative management of
      patients with clinical stage II-III breast cancer under consideration for NST.
      RECOMMENDATIONS: Preoperative or NST is emerging as an important initial strategy
      for the management of invasive breast cancer. From the surgeon's perspective, the
      primary goal of NST is to increase the resectability of locally advanced breast
      cancer, increase the feasibility of breast-conserving surgery and sentinel node
      biopsy, and decrease surgical morbidity. To ensure optimal patient selection and
      efficient patient care, the guideline recommends: (1) baseline breast and
      axillary imaging; (2) minimally invasive biopsies of breast and axillary lesions;
      (3) determination of tumor biomarkers; (4) systemic staging; (5) care
      coordination, including referrals to medical oncology, radiation oncology,
      plastic surgery, social work, and genetic counseling, if indicated; (6)
      initiation of NST; (7) post-NST breast and axillary imaging; and (8) decision for
      surgery based on extent of disease at presentation, patient choice, clinical
      response to NST, and genetic testing results, if performed.

PMID- 26224407
TI  - Clinical Outcome of Esophagectomy in Elderly Patients With and Without
      Neoadjuvant Therapy for Thoracic Esophageal Cancer.
AB  - BACKGROUND: Esophageal cancer occurs predominantly in elderly people. To date,
      there is no standardized treatment protocol for elderly patients with esophageal
      cancer. The aim of the present study was to assess the effect of old age (>= 80
      years) on treatment and outcome of esophageal cancer. METHODS: We divided 722
      patients who underwent esophagectomy between January 2000 and December 2012 into
      4 age groups (<70, >= 70 to <75, >= 75 to <80, and >= 80 years) and analyzed the
      differences among the groups in treatment strategy (preoperative treatment and
      surgery) and short- and long-term outcome after esophagectomy. RESULTS:
      Preoperative chemotherapy was significantly less frequently used for the
      octogenarians than the other groups. Three-field lymphadenectomy was less
      frequently used with increasing age. Advanced age tended to be associated with
      higher frequency of postoperative pulmonary and cardiovascular complications, but
      not with change in mortality rate, compared with younger patients. The overall
      survival rate was significantly lower in patients of the group >= 75 to <80 and
      group >= 80, compared with group<70 (p = 0.011, p = 0.002). Advanced age, low
      body mass index, postoperative complications, and pathological stage were
      independent and significant prognostic factors in elderly patients who underwent
      esophagectomy. CONCLUSIONS: Elderly patients aged 75 years and more, especially
      octogenarians, showed relatively poor prognosis compared with younger patients
      partly because they less often received neoadjuvant therapy. Aggressive treatment
      may be recommended for elderly patients after taking into careful consideration
      the overall physical condition.

PMID- 26224408
TI  - Novel Homozygous Mutation of the Internal Translation Initiation Start Site of
      VHL is Exclusively Associated with Erythrocytosis: Indications for Distinct
      Functional Roles of von Hippel-Lindau Tumor Suppressor Isoforms.
AB  - Congenital secondary erythrocytosis is a rare disorder characterized by increased
      red blood cell production. An important cause involves defects in the oxygen
      sensing pathway, in particular the PHD2-VHL-HIF axis. Mutations in VHL are also
      associated with the von Hippel-Lindau tumor predisposition syndrome. The
      differences in phenotypic expression of VHL mutations are poorly understood. We
      report on three patients with erythrocytosis, from two unrelated families. All
      patients show exceptionally high erythropoietin (EPO) levels, and are homozygous
      for a novel missense mutation in VHL: c.162G>C p.(Met54Ile). The c.162G>C
      mutation is the most upstream homozygous VHL mutation described so far in
      patients with erythrocytosis. It abolishes the internal translational start
      codon, which directs expression of VHLp19, resulting in the production of only
      VHLp30. The exceptionally high EPO levels and the absence of VHL-associated
      tumors in the patients suggest that VHLp19 has a role for regulating EPO levels
      that VHLp30 does not have, whereas VHLp30 is really the tumor suppressor isoform.

PMID- 26224409
TI  - On the quest for stress-free surgery - a response.

PMID- 26224410
TI  - Monitoring of reversible boronic acid-diol interactions by fluorine NMR
      spectroscopy in aqueous media.
AB  - Recognition and sensing of various biologically relevant species using boronic
      acid-based chemosensors have become increasingly popular over the last few years.
      Herein, we describe a new convenient method for monitoring boronic acid-diol
      interactions in aqueous media based on (19)F NMR spectroscopy with fluorinated
      boronic acid probes. 

PMID- 26224411
TI  - Arabidopsis GERANYLGERANYL DIPHOSPHATE SYNTHASE 11 is a hub isozyme required for
      the production of most photosynthesis-related isoprenoids.
AB  - Most plastid isoprenoids, including photosynthesis-related metabolites such as
      carotenoids and the side chain of chlorophylls, tocopherols (vitamin E),
      phylloquinones (vitamin K), and plastoquinones, derive from geranylgeranyl
      diphosphate (GGPP) synthesized by GGPP synthase (GGPPS) enzymes. Seven out of 10
      functional GGPPS isozymes in Arabidopsis thaliana reside in plastids. We aimed to
      address the function of different GGPPS paralogues for plastid isoprenoid
      biosynthesis. We constructed a gene co-expression network (GCN) using GGPPS
      paralogues as guide genes and genes from the upstream and downstream pathways as
      query genes. Furthermore, knock-out and/or knock-down ggpps mutants were
      generated and their growth and metabolic phenotypes were analyzed. Also,
      interacting protein partners of GGPPS11 were searched for. Our data showed that
      GGPPS11, encoding the only plastid isozyme essential for plant development,
      functions as a hub gene among GGPPS paralogues and is required for the production
      of all major groups of plastid isoprenoids. Furthermore, we showed that the
      GGPPS11 protein physically interacts with enzymes that use GGPP for the
      production of carotenoids, chlorophylls, tocopherols, phylloquinone, and
      plastoquinone. GGPPS11 is a hub isozyme required for the production of most
      photosynthesis-related isoprenoids. Both gene co-expression and protein-protein
      interaction likely contribute to the channeling of GGPP by GGPPS11. 

PMID- 26224416
TI  - High resolution nanomechanical characterization of multi-domain model membranes
      by fast Force Volume.
AB  - Plasma membrane is a complex structure, mainly composed by lipids and proteins,
      which plays a pivotal role in cell metabolism by regulating its selective
      permeability to ions and molecules. According to the "raft hypothesis", lipids in
      the bilayer are not forming a structurally passive solvent, but are rather
      organized in specific domains, which present different structural and functional
      characteristics. The mechanical properties of the lipid part of plasma membrane
      have been recently characterized through Atomic Force Microscopy, by analyzing
      the features of force vs distance curves collected on supported lipid bilayers
      (SLBs). In case of lipid domains sizing from tens to hundreds of nanometers,
      which mimic in a good way the lateral organization of real membranes, a high
      lateral resolution and a large number of curves are often required for properly
      expressing the complexity of the system, with a consequent exponential growth of
      acquisition and processing time. In this paper we propose a method, based on a
      recently developed high speed Force Volume technique and on home-built data
      processing software, for the mechanical characterization of nanostructured SLBs.
      With our software we have been able to process data set composed by tens of
      thousands of curves, collected with a spatial resolution ranging from 8 to 40
      nm/pixel. Multiparametric maps and distribution histograms produced by our
      analysis allowed identifying a specific behavior for each lipid phase in the
      investigated model membranes, even in presence of nanosized features.

PMID- 26224417
TI  - Synthesis and characterization of Ba3Si6O12N2:Eu(2+) phosphor.
AB  - Eu(2+)-doped Ba3Si6O12N2 phosphors were prepared successfully via a modified
      solid-state diffusion method. The phosphors were characterized by X-ray
      diffraction (XRD), scanning electron microscopy (SEM) and photoluminescence
      measurements. These phosphors were effectively excited at 355 nm and an intense
      emission peaking in the range 480 nm to 525 nm in the blue region was observed.
      The optimized dopant concentration was determined to be 1 mol% of Eu(2+) ion. The
      colour coordinates for phosphor were found to be (0.196, 0.326) in the blue
      region. This phosphor may find application for near-ultraviolet (NUV) excited
      lamp phosphors. The thermoluminescence study shows the complex glow curve.
      Trapping parameters (activation energy and frequency factor) were calculated for
      individual deconvoluted peaks by Chen's peak shape method, the initial rise
      method and the whole glow peak method.

PMID- 26224418
TI  - 1.688 g/cm(3) satellite-related repeats: a missing link to dosage compensation
      and speciation.
AB  - Despite the important progress that has been made on dosage compensation (DC), a
      critical link in our understanding of the X chromosome recognition mechanisms is
      still missing. Recent studies in Drosophila indicate that the missing link could
      be a family of DNA repeats populating the euchromatin of the X chromosome. In
      this opinion article, I discuss how these findings add a new fresh twist on the
      DC problem. In the following sections, I first summarize our understanding of DC
      in Drosophila and integrate these recent discoveries into our knowledge of the X
      chromosome recognition problem. Next, I introduce a model according to which,
      1.688 g/cm(3) satellite-related (SR) repeats would be the primary recognition
      elements for the dosage compensation complex. Contrary to the current belief, I
      suggest that the DC system in Drosophila is not conserved and static, but it is
      continuously co-evolving with the target SR repeats. The potential role of the SR
      repeats in hybrid incompatibilities and speciation is also discussed. 

PMID- 26224420
TI  - Morphologic and cytogenetic variables affect the flow cytometric recovery of
      plasma cell myeloma cells in bone marrow aspirates.
AB  - INTRODUCTION: It is widely recognized that plasma cells (PCs) are under
      represented in flow cytometry (FC) studies, but the causes of this phenomenon are
      poorly understood. We sought to study potential variables that affect PC recovery
      by flow cytometry (FC) in the analysis of plasma cell myeloma (PCM). METHODS: We
      retrospectively performed PC differential counts and morphologic assessment on
      PCM peripheral blood (PB) smears, bone marrow (BM) aspirate smears and
      posterythrocyte lysis cytospins. PCs were enumerated by FC, excluding erythroid
      events/debris, and were defined as CD38(bright+), CD45(dim to negative) events.
      PC recovery was calculated as follows: cytospin/aspirate, FC/aspirate, and
      FC/cytospin. RESULTS: Sixty-four BM analyses from 42 patients showed a mean
      aspirate PC% of 32.9 +/- 23.2%. The mean PC% decreased in both the cytospin
      (10.9%) and by FC (8.2%). The difference between PC% in the cytospin and by FC
      was statistically significant (P < 0.03). Mature PC morphology and lower aspirate
      PC% had poorer recovery (P < 0.05) but higher-risk cytogenetics (deletions of 13q
      and TP53) was associated with increased PC recovery. Immunophenotype, heavy chain
      type, and treatment did not affect PC recovery. PB specimens had superior
      recovery compared with BM samples. CONCLUSIONS: Similar to prior reports, the
      greatest loss of PC in BM evaluation occurs between the aspirate and postlysis
      specimens; however, a small amount occurs from further processing. Additional
      morphologic and cytogenetic factors also appear to influence recovery in addition
      to overall PC%.

PMID- 26224419
TI  - Sleep deficits but no metabolic deficits in premanifest Huntington's disease.
AB  - OBJECTIVE: Huntington disease (HD) is a fatal autosomal dominant,
      neurodegenerative condition characterized by progressively worsening motor and
      nonmotor problems including cognitive and neuropsychiatric disturbances, along
      with sleep abnormalities and weight loss. However, it is not known whether sleep
      disturbances and metabolic abnormalities underlying the weight loss are present
      at a premanifest stage. METHODS: We performed a comprehensive sleep and metabolic
      study in 38 premanifest gene carrier individuals and 36 age- and sex-matched
      controls. The study consisted of 2 weeks of actigraphy at home, 2 nights of
      polysomnography and multiple sleep latency tests in the laboratory, and body
      composition assessment using dual energy x-ray absorptiometry scanning with
      energy expenditure measured over 10 days at home by doubly labeled water and for
      36 hours in the laboratory by indirect calorimetry along with detailed cognitive
      and clinical assessments. We performed a principal component analyses across all
      measures within each studied domain. RESULTS: Compared to controls, premanifest
      gene carriers had more disrupted sleep, which was best characterized by a
      fragmented sleep profile. These abnormalities, as well as a theta power (4-7Hz)
      decrease in rapid eye movement sleep, were associated with disease burden score.
      Objectively measured sleep problems coincided with the development of cognitive,
      affective, and subtle motor deficits and were not associated with any metabolic
      alterations. INTERPRETATION: The results show that among the earliest
      abnormalities in premanifest HD is sleep disturbances. This raises questions as
      to where the pathology in HD begins and also whether it could drive some of the
      early features and even possibly the pathology.

PMID- 26224421
TI  - An integrative review: understanding driving retirement decisions for individuals
      living with a dementia.
AB  - AIM: To synthesise primary research exploring decision making practices used to
      determine the time to retire from driving for individuals living with a dementia.
      BACKGROUND: Driving requires complex cognitive and physical skills potentially
      compromised due to the progressive nature of dementia. Whilst on-road assessments
      are considered reliable indicators of driving capacity by clinicians, drivers
      with dementia disagree. DESIGN: Integrative literature review informed by
      Whittemore & Knafl (2005). DATA SOURCES: Electronic database search of Medline,
      CINAHL, Web of Science, Google Scholar 1997-2012; and incremental hand search.
      REVIEW METHODS: Primary studies published in peer reviewed journals were
      appraised against quality assessment criteria using CASP methodological
      assessment tools. RESULTS: A total of 43 studies were retained for synthesis. Key
      findings were abstracted and a themes matrix was generated to identify patterns
      of meaning. Six themes emerged: (i) dementia may compromise the complex task of
      driving; (ii) defining onset and severity of dementia is problematic; (iii)
      symptom progression impacts on driving skills; (iv) assessment of fitness to
      drive remains subjective; (v) some drivers are reluctant to accept negative
      assessment outcomes; and (vi) the search for effective strategies to enhance
      acceptance of driver retirement continues. CONCLUSION: This integrative
      literature review identified a large body of knowledge exploring the issues of
      driving cessation for drivers with dementia. However a challenge remains for
      practitioners, drivers and their family carers regarding how best to address this
      highly emotive issue. Findings could inform a structured approach to address this
      sensitive topic in a timely manner.

PMID- 26224422
TI  - Evidence for Coexistence of Bulk Superconductivity and Itinerant
      Antiferromagnetism in the Heavy Fermion System CeCo(In(1-x)Cdx)5.
AB  - In the generic phase diagram of heavy fermion systems, tuning an external
      parameter such as hydrostatic or chemical pressure modifies the superconducting
      transition temperature. The superconducting phase forms a dome in the temperature
      tuning parameter phase diagram, which is associated with a maximum of the
      superconducting pairing interaction. Proximity to antiferromagnetism suggests a
      relation between the disappearance of antiferromagnetic order and
      superconductivity. We combine muon spin rotation, neutron scattering, and x-ray
      absorption spectroscopy techniques to gain access to the magnetic and electronic
      structure of CeCo(In(1-x)Cdx)5 at different time scales. Different magnetic
      structures are obtained that indicate a magnetic order of itinerant character,
      coexisting with bulk superconductivity. The suppression of the antiferromagnetic
      order appears to be driven by a modification of the bandwidth/carrier
      concentration, implying that the electronic structure and consequently the
      interplay of superconductivity and magnetism is strongly affected by hydrostatic
      and chemical pressure.

PMID- 26224423
TI  - Hospital admission patterns in adult patients with skin and soft tissue
      infections: Identification of potentially avoidable hospital admissions through a
      retrospective database analysis.
AB  - BACKGROUND: Despite the substantial hospitalization costs associated with the
      management of patients with skin and soft tissue infections (SSTIs) in the
      inpatient setting, there is limited guidance on patients who should be managed in
      the hospital relative to the outpatient setting. Studies have demonstrated that
      SSTI patients without major complications or comorbidities can be successfully
      managed in the outpatient setting. However, there are limited data on current
      hospital admission patterns for patients with SSTI. OBJECTIVES: Given this
      literature gap, this study described the current hospital admission patterns
      among adult patients with SSTI using data from a US hospital research database.
      METHODS: To determine the subset of hospitalized SSTI patients who could likely
      be managed in the outpatient setting (potentially avoidable hospital admissions),
      the distribution of hospital admissions was categorized by infection severity and
      Charlson Comorbidity Index (CCI) score. RESULTS: During the study observational
      period, there were 610,867 medical encounters across 520 hospitals. Of the
      610,867, 125,743 (20.6%) were treated as inpatients. Nearly all patients with
      life-threatening conditions or systemic symptoms or a CCI score of 2 or greater
      were admitted. Among those with no life-threatening conditions and no systemic
      symptoms, admission rates exceeded 10 and 30% for patients with a CCI score of
      zero and 1, respectively. While the admissions rates for these patient
      populations were low, they accounted for nearly 60% of all admissions (75,255 of
      125,743 hospital admissions). On average, patients with CCI score of zero or 1,
      independent of the presence of systemic symptoms, were treated in the hospital
      for about 4 days, costing $6000-$7000 on average. CONCLUSIONS: Given the cost
      associated with the management of patients with SSTIs in the inpatient setting,
      the findings highlight the critical need for healthcare systems to develop well
      defined criteria for hospital admission based on presence of comorbid conditions
      and infection severity.

PMID- 26224424
TI  - Managing MERS-CoV in the healthcare setting.
AB  - Middle East respiratory Syndrome Coronavirus (MERS-CoV) has caused at least 1118
      reported cases in 24 countries with at least 423 deaths worldwide. All cases are
      epidemiologically linked to the Arabian Penninsula with most cases reported from
      the Kingdom of Saudi Arabia. MERS-CoV has three patterns of presentation:
      sporadic isolated cases, small clusters of intra-familial transmission and large
      healthcare-associated infections. The disease presentation varies from
      asymptomatic/mild cases to severe and fatal cases. The source of the virus has
      focused on bats and dromedary camels but the exact mode of disease transmission
      continues to be debated. Current data indicate that the virus spreads from human
      to human through droplet and contact routes, while performing aerosole-generating
      procedures predispose to airborne transmission. The best diagnostic tests rely on
      the identification of MERS-CoV by PCR, and lower respiratory tract samples should
      be favoured for the diagnosis whenever this is possible in order to avoid false
      negative results. Recently, the World Health Organization added serology to the
      list of confirmatory tests. Currently, there is no proven therapy, with
      supportive treatment being the mainstay of treatment. 

PMID- 26224425
TI  - Glycemic control in the critically ill: What have we learned since NICE-SUGAR?
AB  - Since publication of the Normoglycemia in Intensive Care Evaluation - Survival
      Using Glucose Algorithm Regulation trial in 2009, demonstrating increased 90-day
      mortality in a large cohort of critically ill patients treated with the
      intensive, rather than moderate blood glucose (BG) target, enthusiasm has
      dampened for 'tight glucose control' in intensive care units. Nevertheless, a
      burgeoning literature has clarified limitations of the interventional trials of
      intensive insulin therapy in the critically ill and explored key clinical aspects
      of glycemic control in this population. This review provides an overview of the
      last 6 years of research in this field. Topics include advances in understanding
      the domains of glycemic control - hyperglycemia, hypoglycemia and glucose
      variability; the role of diabetic status in modulating the relationship of these
      domains of control to mortality; the importance of premorbid glucose control in
      patients with diabetes; the central role that measurement frequency has in
      determining success in achieving desired BG control and, finally, new data
      exploring time in targeted BG range, a potentially 'unifying' metric. 

PMID- 26224426
TI  - Efficient two-step chemo-enzymatic synthesis of all-trans-retinyl palmitate with
      high substrate concentration and product yield.
AB  - A new two-step chemo-enzymatic approach for highly efficient synthesis of all
      trans-retinyl palmitate is constructed in this study. In the first step, retinyl
      acetate as starting material was fully hydrolyzed to retinol by potassium
      hydroxide. In the hydrolysis system, anhydrous ethanol was the best co-solvent to
      increase the solubility of retinyl acetate. The addition amounts of 5 M potassium
      hydroxide and anhydrous ethanol were 8 and 10 mL against 10 g retinyl acetate,
      respectively, and 100 % hydrolysis rate was obtained. In the second step,
      esterification was catalyzed by immobilized lipase on macroporous acrylic resin
      AB-8 using the extracted retinol and palmitic acid as substrates in non-aqueous
      system. After optimization, the parameters of esterification reaction were
      confirmed as follows: non-aqueous solvent was selected as n-hexane, washing times
      of extraction solution was four times, retinol concentration was 300 g/L,
      substrate molar ratio of retinol to palmitic acid was 1:1.1, the amount of
      immobilized enzyme was 10 g/L, and the esterification temperature was 30  degrees
      C. Under the optimal conditions, this protocol resulted in a 97.5 % yield of all
      trans-retinyl palmitate in 700-L reactor. After purification, all-trans-retinyl
      palmitate was obtained with above 99 % of purity and 88 % of total recovery rate.
      This methodology provides a promising strategy for the large-scale production of
      all-trans-retinyl palmitate.

PMID- 26224427
TI  - Improved biomass and protein production in solid-state cultures of an Aspergillus
      sojae strain harboring the Vitreoscilla hemoglobin.
AB  - The biotechnological value of Aspergillus sojae ATCC 20235 (A. sojae) for
      production of pectinases in solid-state fermentation (SSF) has been demonstrated
      recently. However, a common drawback of fungal solid-state cultures is the poor
      diffusion of oxygen into the fungi that limits its growth and biological
      productivity. The bacterial Vitreoscilla hemoglobin (VHb) has favored the
      metabolism and productivities of various bacterial and yeast strains besides
      alleviating hypoxic conditions of its native host, but the use of VHb in
      filamentous fungi still remains poor explored. Based on the known effects of VHb,
      this study assessed its applicability to improve A. sojae performance in SSF. The
      VHb gene (vgb) under control of the constitutive Aspergillus nidulants gpdA
      promoter was introduced into the genome of A. sojae by Agrobacterium-mediated
      transformation. Successful fungal transformants were identified by fluorescence
      microscopy and polymerase chain reaction (PCR) analyses. In solid-state cultures,
      the content of protease, exo-polygalacturonase (exo-PG), and exo
      polymethylgalacturonase (exo-PMG) of the transformed fungus (A. sojae vgb+)
      improved were 26, 60, and 44 % higher, respectively, in comparison to its
      parental strain (A. sojae wt). Similarly, biomass content was also 1.3 times
      higher in the transformant strain. No significant difference was observed in endo
      polygalacturonase (endo-PG) content between both fungal strains, suggesting
      dissimilar effects of VHb towards different enzymatic productions. Overall, our
      results show that biomass, protease, and exo-pectinase content of A. sojae in SSF
      can be improved by transformation with VHb.

PMID- 26224428
TI  - High Blood Pressure in Sub-Saharan Africa: The Urgent Imperative for Prevention
      and Control.

PMID- 26224430
TI  - Acceptance, commissioning and clinical use of the WOmed T-200 kilovoltage X-ray
      therapy unit.
AB  - OBJECTIVE: The objective of this work was to characterize the performance of the
      WOmed T-200-kilovoltage (kV) therapy machine. METHODS: Mechanical functionality,
      radiation leakage, alignment and interlocks were investigated. Half-value layers
      (HVLs) (first and second HVLs) from X-ray beams generated from tube potentials
      between 30 and 200 kV were measured. Reference dose was determined in water. Beam
      start-up characteristics, dose linearity and reproducibility, beam flatness, and
      uniformity as well as deviations from inverse square law were assessed. Relative
      depth doses (RDDs) were determined in water and water-equivalent plastic. The
      quality assurance program included a dosimetry audit with thermoluminescent
      dosemeters. RESULTS: All checks on machine performance were satisfactory. HVLs
      ranged between 0.45-4.52 mmAl and 0.69-1.78 mmCu. Dose rates varied between 0.2
      and 3 Gy min(-1) with negligible time-end errors. There were differences in
      measured RDDs from published data. Beam outputs were confirmed with the dosimetry
      audit. The use of published backscatter factors was implemented to account for
      changes in phantom scatter for treatments with irregularly shaped fields.
      CONCLUSION: Guidance on the determination of HVL and RDD in kV beams can be
      contradictory. RDDs were determined through measurement and curve fitting. These
      differed from published RDD data, and the differences observed were larger in the
      low-kV energy range. ADVANCES IN KNOWLEDGE: This article reports on the
      comprehensive and novel approach to the acceptance, commissioning and clinical
      use of a modern kV therapy machine. The challenges in the dosimetry of kV beams
      faced by the medical physicist in the clinic are highlighted.

PMID- 26224429
TI  - Frontal and frontoparietal injury differentially affect the ipsilateral
      corticospinal projection from the nonlesioned hemisphere in monkey (Macaca
      mulatta).
AB  - Upper extremity hemiplegia is a common consequence of unilateral cortical stroke.
      Understanding the role of the unaffected cerebral hemisphere in the motor
      recovery process has been encouraged, in part, by the presence of ipsilateral
      corticospinal projections (iCSP). We examined the neuroplastic response of the
      iCSP from the contralesional primary motor cortex (cM1) hand/arm area to spinal
      levels C5-T1 after spontaneous long-term recovery from isolated frontal lobe
      injury and isolated frontoparietal injury. High-resolution tract tracing,
      stereological, and behavioral methodologies were applied. Recovery from frontal
      motor injury resulted in enhanced numbers of terminal labeled boutons in the iCSP
      from cM1 compared with controls. Increases occurred in lamina VIII and the
      adjacent ventral sectors of lamina VII, which are involved in axial/proximal limb
      sensorimotor processing. Larger frontal lobe lesions were associated with greater
      numbers of terminal boutons than smaller frontal lobe lesions. In contrast,
      frontoparietal injury blocked this response; total bouton number was similar to
      controls, demonstrating that disruption of somatosensory input to one hemisphere
      has a suppressive effect on the iCSP from the nonlesioned hemisphere. However,
      compared with controls, elevated bouton numbers occurred in lamina VIII, at the
      expense of lamina VII bouton labeling. Lamina IX boutons were also elevated in
      two frontoparietal lesion cases with extensive cortical injury. Because laminae
      VIII and IX collectively harbor axial, proximal, and distal motoneurons,
      therapeutic intervention targeting the ipsilateral corticospinal linkage from cM1
      may promote proximal, and possibly distal, upper-limb motor recovery following
      frontal and frontoparietal injury.

PMID- 26224431
TI  - Ischaemic heart disease incidence and mortality in an extended cohort of Mayak
      workers first employed in 1948-1982.
AB  - OBJECTIVE: Incidence and mortality from ischaemic heart disease (IHD) was studied
      in an extended cohort of 22,377 workers first employed at the Mayak Production
      Association during 1948-82 and followed up to the end of 2008. METHODS: Relative
      risks and excess relative risks per unit dose (ERR/Gy) were calculated based on
      the maximum likelihood using Epicure software (Hirosoft International
      Corporation, Seattle, WA). Dose estimates used in analyses were provided by an
      updated "Mayak Worker Dosimetry System-2008". RESULTS: A significant increasing
      linear trend in IHD incidence with total dose from external gamma-rays was
      observed after having adjusted for non-radiation factors and dose from internal
      radiation {ERR/Gy = 0.10 [95% confidence interval (CI): 0.04 to 0.17]}. The pure
      quadratic model provided a better fit of the data than did the linear one. No
      significant association of IHD mortality with total dose from external gamma-rays
      after having adjusted for non-radiation factors and dose from internal alpha
      radiation was observed in the study cohort [ERR/Gy = 0.06 (95% CI: <0 to 0.15)].
      A significant increasing linear trend was observed in IHD mortality with total
      absorbed dose from internal alpha radiation to the liver after having adjusted
      for non-radiation factors and dose from external gamma-rays in both the whole
      cohort [ERR/Gy = 0.21 (95% CI: 0.01 to 0.58)] and the subcohort of workers
      exposed at alpha dose <1.00 Gy [ERR/Gy = 1.08 (95% CI: 0.34 to 2.15)]. No
      association of IHD incidence with total dose from internal alpha radiation to the
      liver was found in the whole cohort after having adjusted for non-radiation
      factors and external gamma dose [ERR/Gy = 0.02 (95% CI: not available to 0.10)].
      Statistically significant dose effect was revealed in the subcohort of workers
      exposed to internal alpha radiation at dose to the liver <1.00 Gy [ERR/Gy = 0.44
      (95% CI: 0.09 to 0.85)]. CONCLUSION: This study provides strong evidence of IHD
      incidence and mortality association with external gamma-ray exposure and some
      evidence of IHD incidence and mortality association with internal alpha-radiation
      exposure. ADVANCES IN KNOWLEDGE: It is the first time the validity of internal
      radiation dose estimates has been shown to affect the risk of IHD incidence.

PMID- 26224432
TI  - Re.: Russell and Burch's 3Rs Then and Now.

PMID- 26224433
TI  - Blood Lipid Distribution, Aortic Cholesterol Concentrations, and Selected
      Inflammatory and Bile Metabolism Markers in Syrian Hamsters Fed a Standard
      Breeding Diet.
AB  - Hamsters are often used to determine the effects of various dietary ingredients
      on the development of cardiovascular disease (CVD). The study was conducted to
      obtain baseline data on CVD risk factors and mRNA expression of selected genes in
      hamsters fed a standard maintenance diet (STD) for 24 wk, beginning when animals
      were 7 wk old. Plasma triacylglycerol and aortic cholesteryl ester concentrations
      did not significantly change during the study. Total plasma cholesterol (75.9
      127.9 mg/dL), LDL- (3.2-12.2 mg/dL), and HDL- (53.8-98.9 mg/dL) cholesterols
      increased over the 24wk study. Aortic total cholesterol increased from 9.72 to
      12.20 MUg/mg protein, whereas aortic cholesteryl ester, a measure of
      atherosclerosis development, was less than 0.18 MUg/mg protein throughout the
      study. The expression of hepatic endothelin 1, peroxisome proliferator-activated
      receptor alpha, and hepatic cholesterol 7-alpha-hydroxylase mRNA did not change
      throughout the study, indicating that fatty acid beta-oxidation and cholesterol
      metabolism remained consistent. The mRNA expression of ATP-binding cassette,
      subfamily B member 11 increased between wk 0 and 8 but then remained unchanged,
      suggesting increased requirements for cholesterol in early growth. These results
      indicate that the consumption of a STD does not increase atherosclerotic disease
      risk factors in golden Syrian hamsters through 31 wk of age. 

PMID- 26224434
TI  - Hematology and Clinical Chemistry Measures During and After Pregnancy and Age-
      and Sex-Specific Reference Intervals in African Green Monkeys (Chlorocebus
      aethiops sabaeus).
AB  - Clinical decisions and experimental analyses often involve the assessment of
      hematology and clinical chemistry. Using clinical pathology to assess the health
      status of NHP in breeding colonies or data from studies than involve pregnancy
      can often be complicated by pregnancy status. This study had 2 objectives
      regarding the hematology and clinical chemistry of African green monkeys (AGM,
      Chlorocebus aethiops sabaeus): 1) to compare pregnant or recently postpartum
      animals with nonpregnant, nonlactating animals and 2) to create age- and sex
      specific reference intervals. Subjects in this study were 491 AGM from the Vervet
      Research Colony of the Wake Forest University Primate Center. Results indicated
      that changes in BUN, serum total protein, albumin, ALP, GGT, calcium, phosphorus,
      sodium, potassium, cholesterol, total CO2, globulins, lipase, amylase, WBC,
      neutrophils, lymphocytes, platelets, RBC, Hgb, and Hct occur during pregnancy and
      the postpartum period. Age- and sex-specific reference intervals consistent with
      guidelines from the American Society for Veterinary Clinical Pathology were
      established and further expand the understanding of how to define health in AGM
      on the basis of clinical pathology. The combination of understanding the changes
      that occur in pregnancy and postpartum and expansive reference intervals will
      help guide clinical and experimental decisions. 

PMID- 26224435
TI  - A Simple and Reliable Method for Early Pregnancy Detection in Inbred Mice.
AB  - The study of normal and abnormal development typically requires precise embryonic
      staging. In mice, this task is accomplished through timed matings and the
      detection of a copulation plug. However, the presence of a plug is not a
      definitive indicator of true pregnancy, particularly in inbred mice, in which
      false-pregnancy rates have been reported to be 50% or higher, depending on the
      strain. This high rate poses considerable financial and animal use burdens
      because manipulation of the putative dam is often required before pregnancy can
      be confirmed by palpation or visual inspection. To address this problem, we
      examined weight gain in a population of 275 wildtype C57BL/6J mice (age, 12 wk or
      older) between the time of plug detection and during early embryogenesis
      (gestational days 7 to 10). In this population, assessing pregnancy according to
      the presence of a plug alone yielded a 37.1% false-positive rate. Pregnant mice
      gained an average of 3.49 g, whereas non-pregnant mice gained only 1.15 g.
      Beginning at gestational day 7.75, implementing an optimal weight-gain
      discrimination threshold of 1.75 g reduced the false-positive rate to 10.5%,
      without excluding any pregnant mice. These results were consistent with those
      from younger (age, 8 wk) wildtype C57BL/6J and FVB/NTac female mice, suggesting
      broad applicability of this method across age and strain. Our findings provide a
      simple and effective method for reducing animal use and study costs. 

PMID- 26224436
TI  - Characteristics of Vibration that Alter Cardiovascular Parameters in Mice.
AB  - We hypothesized that short-term exposure of mice to vibration within a frequency
      range thought to be near the resonant frequency range of mouse tissue and at an
      acceleration of 0 to 1 m/s(2) would alter heart rate (HR) and mean arterial
      pressure (MAP). We used radiotelemetry to evaluate the cardiovascular response to
      vibration in C57BL/6 and CD1 male mice exposed to vertical vibration of various
      frequencies and accelerations. MAP was consistently increased above baseline
      values at an acceleration near 1 m/s(2) and a frequency of 90 Hz in both strains,
      and HR was increased also in C57BL/6 mice. In addition, MAP increased at 80 Hz in
      individual mice of both strains. When both strains were analyzed together, mean
      MAP and HR were increased at 90 Hz at 1 m/s(2), and HR was increased at 80 Hz at
      1 m/s(2). No consistent change in MAP or HR occurred when mice were exposed to
      frequencies below 80 Hz or above 90 Hz. The increase in MAP and HR occurred only
      when the mice had conscious awareness of the vibration, given that these changes
      did not occur when anesthetized mice were exposed to vibration. Tested vibration
      acceleration levels lower than 0.75 m/s(2) did not increase MAP or HR at 80 or 90
      Hz, suggesting that a relatively high level of vibration is necessary to increase
      these parameters. These data are important to establish the harmful frequencies
      and accelerations of environmental vibration that should be minimized or avoided
      in mouse facilities. 

PMID- 26224437
TI  - Effects of Habitat Complexity on Pair-Housed Zebrafish.
AB  - Sexually mature zebrafish were housed as single male-female pairs with or without
      plastic vegetation for 1, 5, or 10 d for comparison of whole-body cortisol
      measured by radioimmunoassay. Individually housed male zebrafish were used as
      controls. In the fish that were pair-housed without vegetation (NVeg), one animal
      died in 5 of 24 pairs, and one animal was alive but wounded in an additional
      pair. No deaths or wounds occurred in the fish that were pair-housed with
      vegetation (Veg). Cortisol levels did not differ between the treatment groups on
      day 1. On day 5, cortisol values were higher in the Veg group than in the
      individually housed fish (P < 0.0005) and the NVeg fish (P = 0.004). On day 10,
      the relationships were inversed: cortisol levels had risen in the individually
      housed and NVeg groups and had fallen to baseline levels in the Veg group.
      Cortisol values on day 10 were lower in the Veg group than in the individually
      housed (P = 0.004) and NVeg (P = 0.05) groups. Cortisol levels in individually
      housed male zebrafish increased over time. Although this study did not
      demonstrate a reduction in cortisol levels associated with providing vegetation,
      this enrichment prevented injury and death from fighting. These findings show how
      commonly used housing situations may affect the wellbeing of laboratory
      zebrafish. 

PMID- 26224438
TI  - Alopecia in Outdoor Group- and Corral-Housed Baboons (Papio hamadryas spp.).
AB  - Alopecia has been reported to occur in several species of captive NHP. Much of
      this research has focused on macaque monkeys; whether other primate species such
      as baboons are affected similarly is unknown. Because alopecia can be a focus of
      inspectors and a possible marker of wellbeing, the purpose of the current study
      was to survey the occurrence of alopecia in 2 baboon populations and to identify
      potential risk factors. Subjects were 262 group-housed and 279 corral-housed
      baboons. Alopecia was assessed cage-side (group-housed) and on sedated animals
      (corral-housed). Although alopecia was mild in both populations, there were
      significant effects of season and sex. Alopecia was greater in the winter (group
      housed) and the fall (corral-housed) and in female baboons. In addition, the
      group-housed baboons showed a significant negative effect of age and a lesser
      effect of group size on alopecia. These results demonstrate that variables other
      than those associated with animal management practices can affect hair loss in
      baboons. 

PMID- 26224439
TI  - Decision Making and the IACUC: Part 1- Protocol Information Discussed at Full
      Committee Reviews.
AB  - IACUC protocols can be reviewed by either the full committee or designated
      members. Both review methods use the principles of the 3 Rs (reduce, refine,
      replace) as the overarching paradigm, with federal regulations and policies
      providing more detailed guidance. The primary goal of this study was to determine
      the frequency of topics discussed by IACUC during full-committee reviews and
      whether the topics included those required for consideration by IACUC (for
      example, pain and distress, number of animals used, availability of alternatives,
      skill and experience of researchers). We recorded and transcribed 87 protocol
      discussions undergoing full-committee review at 10 academic institutions. Each
      transcript was coded to capture the key concepts of the discussion and analyzed
      for the frequency of the codes mentioned. Pain and distress was the code
      mentioned most often, followed by the specific procedures performed, the study
      design, and the completeness of the protocol form. Infrequently mentioned topics
      were alternatives to animal use or painful or distressful procedures, the
      importance of the research, and preliminary data. Not all of the topics required
      to be considered by the IACUC were openly discussed for all protocols, and many
      of the discussions were limited in their depth. 

PMID- 26224440
TI  - Contribution of Endemic Listeriosis to Spontaneous Abortion and Stillbirth in a
      Large Outdoor-housed Colony of Rhesus Macaques (Macaca mulatta).
AB  - Listeria monocytogenes is an endemic agent in the primate population at the
      California National Primate Research Center and has been associated with both
      sporadic cases and a general outbreak of pregnancy failures. The primary
      objective of this study was to verify the incidence of L. monocytogenes
      associated abortion and fetal deaths in the Center's outdoor breeding colony. In
      addition, we sought to compare the group of female macaques that presented with
      Listeria-associated abortion with both those with nonlisteria-associated abortion
      and animals with successful pregnancy outcome. We calculated the incidence of L.
      monocytogenes-associated abortion and stillbirth by dividing the number of
      positive L. monocytogenes cultures from aborted fetuses by the number of pregnant
      female macaques from 1989 through 2009. To compare the pregnancy outcome of
      female macaques that have presented L. monocytogenes-associated abortion and
      stillbirth, we created 2 control groups: female macaques with successful
      pregnancy outcomes during the 1999 breeding season and animals with nonlisteria
      associated pregnancy failure. These macaques were followed for 2 subsequent
      breeding seasons. The results showed a range in the incidence of L. monocytogenes
      associated abortion and stillbirth from 0% to 8.39% throughout the 1989 to 2009
      breeding seasons. In addition, the Listeria-associated abortion group did not
      present statistically significant differences in fertility and abortion rates
      when compared with the control groups. We conclude that although L. monocytogenes
      is an endemic agent at the Center's outdoor breeding colony, the agent's
      incidence varied in significance. Furthermore, an episode of L. monocytogenes
      associated abortion did not affect subsequent pregnancies.

PMID- 26224441
TI  - Analgesic Efficacy of Firocoxib, a Selective Inhibitor of Cyclooxygenase 2, in a
      Mouse Model of Incisional Pain.
AB  - Pain management in laboratory animals is generally accomplished by using opioids
      and NSAIDs. However, opioid use is hindered by controlled substance requirements
      and a relatively short duration of action. In this study, we compared the
      analgesic efficacy of firocoxib (a cyclooxygenase-2-selective NSAID) with that of
      buprenorphine in the mouse model of plantar incisional pain by objective
      measurement of mechanical allodynia and thermal hyperalgesia using von Frey and
      Hargreaves equipment, respectively. Our experimental design included 5 treatment
      groups: firocoxib at 10 mg/kg IP every 24 h (F10 group); firocoxib at 20 mg/kg IP
      every 24 h (F20); buprenorphine at 0.2 mg/kg SC every 8 h; intraperitoneal normal
      saline every 24 h; and sham group (anesthesia, no incision) treated with
      firocoxib at 20 mg/kg IP every 24 h (sham+F20). All mice underwent nociceptive
      assays at 24 h before and 4, 24, 48, and 72 h after surgery. Buprenorphine
      alleviated allodynia at all time points after incision. The F10 treatment
      alleviated allodynia at 4, 24, and 48 h, whereas F20 alleviated allodynia at 24,
      48, and 72 h. None of the treatments alleviated thermal hyperalgesia at 4h.
      Except for F10 and buprenorphine at 24 h, all treatments alleviated thermal
      hyperalgesia at 24, 48, and 72 h. No significant differences were noted between
      the 2 doses of firocoxib and buprenorphine regarding mechanical allodynia and
      thermal hyperalgesia at all time points. In conclusion, the analgesic efficacy of
      firocoxib is comparable to that of buprenorphine in this mouse pain model. 

PMID- 26224442
TI  - Efficacy of Tramadol as a Sole Analgesic for Postoperative Pain in Male and
      Female Mice.
AB  - Tramadol is a centrally acting weak MU opioid agonist that has few of the adverse
      side effects common to other opioids. Little work has been done to establish an
      effective analgesic dose of tramadol specific for surgical laparotomy and
      visceral manipulation in mice. We used general appearance parameters to score
      positive indicators of pain including posture, coat condition, activity,
      breathing, and interactions with other mice, activity events (that is, the number
      of times each mouse stretched up in a 3-min period) used as an indicator of
      decreased pain, von Frey fibers, and plasma levels of corticosterone to determine
      whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and
      female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a
      model of postoperative pain. In male mice, none of the markers differed between
      groups that received tramadol (regardless of dose) and the saline-treated
      controls. However, general appearance scores and plasma corticosterone levels
      were lower in female mice that received 80 mg/kg tramadol compared with saline.
      In summary, for severe postoperative pain after laparotomy and aseptic
      typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested.
      Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this
      dose is very close to the threshold reported to cause toxic side effects, such as
      tremors and seizures. Therefore, we do not recommend the use of tramadol as a
      sole analgesic in this mouse model of postoperative pain. 

PMID- 26224444
TI  - Assessment of an Orofacial Operant Pain Assay as a Preclinical Tool for
      Evaluating Analgesic Efficacy in Rodents.
AB  - A model system capable of providing clinically relevant analgesic doses with
      minimal trauma has been elusive in laboratory animal medicine. Our laboratory has
      developed an orofacial operant pain system that effectively discriminates between
      non-noxious and noxious thermal stimuli in rats and mice. Male and female rats
      (Crl:SD) and mice (Crl:SKR-HR(hr)) were trained to perform a task (placing their
      face through an opening and having their cheeks stay in contact with thermodes)
      to receive a reward (a solution of sweetened condensed milk). Currently accepted
      doses of buprenorphine were tested by using a crossover design. Pain was induced
      in both species by sensitizing the depilated skin over both cheeks with capsaicin
      cream or by creating a surgical incision (rats only) and then allowing the
      animals to contact a temperature-regulated thermode while obtaining a reward.
      Optimal antinociceptive doses included 0.05 and 0.1 mg/kg in male mice but only
      0.05 mg/kg in female mice. In rats, optimal antinociceptive doses included 0.03
      and 0.05 mg/kg for male rats but only 0.03 mg/kg for female rats. The 2 pain
      induction models in rats (capsaicin cream and surgical incision) did not differ.
      Our orofacial operant pain assay can determine clinically relevant analgesic
      doses for rodents in a preclinical assay. The automated, investigator-independent
      nature of the assay, in conjunction with its high sensitivity, makes this method
      an improvement over traditional noninvasive methods, providing better data for
      developing optimal analgesic recommendations for rats and mice.

PMID- 26224443
TI  - Efficacy of Common Analgesics for Postsurgical Pain in Rats.
AB  - Each year, millions of rats undergo surgery for research purposes and receive
      analgesics to alleviate pain. We sought to evaluate the efficacy of common
      analgesics in tests of hot-plate nociception and postsurgical pain by using the
      Rat Grimace Scale. Rats received a single dose of one of several drug-dose
      combinations and were tested by using the hot-plate test (acute pain) or after
      laparotomy (with either prophylactic or intraoperative analgesic). The efficacy
      of analgesics for hot-plate pain was generally not predictive of efficacy for
      surgical pain. Carprofen and ketoprofen were rarely effective in any of the
      conditions tested. With the exception of the opioid buprenorphine, several of the
      drugs we tested required higher-than-recommended doses to alleviate pain. Taken
      together, our data suggest that current analgesic use frequently is insufficient,
      and many rats may experience significant postsurgical pain even when analgesics
      are used in commonly recommended doses. 

PMID- 26224445
TI  - Use of Neonatal Fostering To Remove Helicobacter spp. from Deer Mice (Peromyscus
      maniculatus).
AB  - Helicobacter species can be found in a wide variety of animals and remain common
      contaminants of laboratory rodents. Fostering of neonatal pups has been used to
      eliminate Helicobacter spp. from various laboratory rodents, including laboratory
      mice and gerbils. Deer mice (Peromyscus maniculatus) from a captive colony
      enzootic for at least one Helicobacter species were mated, and the pups produced
      were fostered on laboratory mice 24 h after birth. After 2 rounds of fostering,
      both foster dams and pups were free of Helicobacter spp. as determined by fecal
      PCR analysis. Removal of Helicobacter infection through neonatal fostering has
      not been described previously for Peromyscus maniculatus. 

PMID- 26224447
TI  - Corrigendum: Parkinson-causing alpha-synuclein missense mutations shift native
      tetramers to monomers as a mechanism for disease initiation.

PMID- 26224446
TI  - Long non-coding RNA Fer-1-like protein 4 suppresses oncogenesis and exhibits
      prognostic value by associating with miR-106a-5p in colon cancer.
AB  - Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been confirmed to
      play crucial regulatory roles in tumor progression. It exerts an impact on tumor
      suppression and functions as a competing endogenous RNA (ceRNA) by sponging miR
      106a-5p in gastric cancer. However, its clinical significance in colon cancer is
      completely unknown. The aim of the present study was to annotate the role of
      FER1L4 and its clinical value in colon cancer. The results showed the aberrant
      expression of FER1L4 and miR-106a-5p in colon cancer tissues. In addition,
      significant negative correlation between FER1L4 and miR-106a-5p expression levels
      was observed. Among the colon cancer cell lines, FER1L4 levels were relatively
      lower, with concurrent high levels of miR-106a-5p. Restoration of FER1L4
      decreased the expression of miR-106a-5p, and had a significant influence on colon
      cancer cell proliferation, migration and invasion. The FER1L4 expression was
      correlated with depth of tumor invasion, lymph node metastasis, vascular invasion
      and clinical stage. Moreover, striking differences in overall survival and
      disease-free survival were observed for the cases with both low FER1L4 expression
      and high miR-106a-5p expression compared with cases with high FER1L4 expression
      and low miR-106a-5p expression. Circulating FER1L4 and miR-106a-5p levels were
      decreased and increased, respectively, in colon cancer patients after surgery.
      Our findings indicated that FER1L4 could exert a tumor suppressive impact on
      colon cancer, which at least, in part, through suppressing miR-106a-5p
      expression, and depletion of FER1L4, alone or combined with overexpression of miR
      106a-5p, is predictive of poor prognosis in colon cancer and may play a crucial
      role in cancer prevention and treatment. 

PMID- 26224448
TI  - Drifting Diaphyses: Asymmetry in Diametric Growth and Adaptation Along the
      Humeral and Femoral Length.
AB  - This study quantifies regional histomorphological variation along the human
      humeral and femoral diaphysis in order to gain information on diaphyseal growth
      and modeling drift patterns. Three thin sections at 40, 50, and 60% bone length
      were prepared from a modern Mexican skeletal sample with known age and sex to
      give a longitudinal perspective on the drifting cortex (12 adults and juveniles
      total, 7 male and 5 female). Point-count techniques were applied across eight
      cross-sectional regions of interest using the starburst sampling pattern to
      quantify percent periosteal and endosteal primary lamellar bone at each
      diaphyseal level. The results of this study show a posterio-medial drift pattern
      in the humerus with a posterior rotational trend along the diaphysis. In the
      femur, we observed a consistent lateral to anteriolateral drift and an increase
      in primary lamellar bone area of both, periosteal and endosteal origin, towards
      the distal part of the diaphysis. These observations characterize drifting
      diaphyses in greater detail, raising important questions about how to resolve
      microscopic and macroscopic cross-sectional analysis towards a more complete
      understanding of bone growth and mechanical adaptation. Accounting for modeling
      drift has the potential to positively impact age and physical activity
      estimation, and explain some of the significant regional variation in bone
      histomorphology seen within (and between) bone cross-sections due to differing
      ages of tissue formation. More study is necessary, however, to discern between
      possible drift scenarios and characterize populational variation.

PMID- 26224449
TI  - Comment on: "Healthy Decisions: Towards Uncertainty Tolerance in Healthcare
      Policy".

PMID- 26224450
TI  - Regulation of Escherichia coli RNase III activity.
AB  - Bacterial cells respond to changes in the environment by adjusting their
      physiological reactions. In cascades of cellular responses to stresses of various
      origins, rapid modulation of RNA function is known to be an effective biochemical
      adaptation. Among many factors affecting RNA function, RNase III, a member of the
      phylogenetically highly conserved endoribonuclease III family, plays a key role
      in posttranscriptional regulatory pathways in Escherichia coli. In this review,
      we provide an overview of the factors affecting RNase III activity in E. coli. 

PMID- 26224451
TI  - Aliisedimentitalea scapharcae gen. nov., sp. nov., isolated from ark shell
      Scapharca broughtonii.
AB  - A Gram-negative, aerobic, non-spore-forming, motile and ovoid or rod-shaped
      bacterial strain, designated MA2-16(T), was isolated from ark shell (Scapharca
      broughtonii) collected from the South Sea, South Korea. Strain MA2-16(T) was
      found to grow optimally at 30 degrees C, at pH 7.0-8.0 and in the presence of
      2.0% (w/v) NaCl. Neighbour-joining, maximum-likelihood and maximum-parsimony
      phylogenetic trees based on 16S rRNA gene sequences revealed that strain MA2
      16(T) clustered with the type strain of Sedimentitalea nanhaiensis. The novel
      strain exhibited a 16S rRNA gene sequence similarity value of 97.1% to the type
      strain of S. nanhaiensis. In the neighbour-joining phylogenetic tree based on
      gyrB sequences, strain MA2-16(T) formed an evolutionary lineage independent of
      those of other taxa. Strain MA2-16(T) contained Q-10 as the predominant
      ubiquinone and C18:1 omega7c and 11-methyl C18:1 omega7c as the major fatty
      acids. The major polar lipids of strain MA2-16(T) were phosphatidylcholine,
      phosphatidylglycerol, phosphatidylethanolamine, an unidentified aminolipid and an
      unidentified lipid. The DNA G+C content of strain MA2-16(T) was 57.7 mol% and its
      DNA-DNA relatedness values with the type strains of S. nanhaiensis and some
      phylogenetically related species of the genera Leisingera and Phaeobacter were 13
      24%. On the basis of the data presented, strain MA2-16(T) is considered to
      represent a novel genus and novel species within the family Rhodobacteraceae, for
      which the name Aliisedimentitalea scapharcae gen. nov., sp. nov. is proposed. The
      type strain is MA2-16(T) (=KCTC 42119(T) =CECT 8598(T)). 

PMID- 26224452
TI  - Description of a novel pectin-degrading bacterial species Prevotella pectinovora
      sp. nov., based on its phenotypic and genomic traits.
AB  - Five strictly anaerobic Gram-negative bacterial strains, P4-65, P4-76(T), P5-60,
      P5-119, and P5-125, presumably belonging to the genus Prevotella were isolated
      from pig fecal samples. Strains were tested for various phenotypic traits and
      nearcomplete genome sequences were obtained and analyzed. Phylogenetic analysis
      based on 16S rRNA gene sequences and multilocus sequence analysis based on five
      conserved genes confirmed that the strains belong to the genus Prevotella,
      revealing that they represent a novel and discrete lineage distinct from other
      known species of this genus. The size of the genome of the isolated strains is 3
      3.3 Mbp, and the DNA G+C content is 47.5-48.1 mol%. The isolates are strictly
      anaerobic, rod-shaped with rounded ends, non-motile and non-spore-forming. The
      main fermentation products are succinate and acetate, with minor concentrations
      of isovalerate, propionate and isobutyrate. Hydrogen is also produced. Major
      cellular fatty acids consist of anteiso-C(15:0) and iso-C(15:0), and a number of
      additional acids are present in lower concentrations. A substantial portion of
      genes involved in carbohydrate utilization is devoted to pectin degradation and
      utilization, while those supporting growth on xylan in ruminal Prevotella could
      not have been revealed. On the basis of the presented results, a novel species,
      Prevotella pectinovora sp. nov. is proposed. The type strain is P4-76(T) (=DSM
      29996(T) =ZIM B1020(T)).

PMID- 26224453
TI  - Isolation of an algicide from a marine bacterium and its effects against the
      toxic dinoflagellate Alexandrium catenella and other harmful algal bloom species.
AB  - The aim of this study was to isolate and identify bacteria demonstrating an
      algicidal effect against Alexandrium catenella and to determine the activity and
      range of any algicide discovered. The morphological and biochemical attributes of
      an algicidal bacterium, isolate YS-3, and analysis of its 16S rRNA gene sequence
      revealed it to be a member of the genus Brachybacterium. This organism,
      designated Brachybacterium sp. YS-3, showed the greatest effect against A.
      catenella cells of all bacteria isolated, and is assumed to produce secondary
      metabolites. When 10% solutions of culture filtrates from this strain were
      applied to A. catenella cultures, over 90% of cells were killed within 9 h.
      Bioassay-guided isolation of the algicide involved led to the purification and
      identification of an active compound. Based on physicochemical and spectroscopic
      data, including nuclear magnetic resonance and mass analyses, this compound was
      identified as 1-acetyl-beta-carboline. This algicide showed significant activity
      against A. catenella and a wide range of harmful algal bloom (HAB)-forming
      species. Taken together, our results suggest that Brachybacterium sp. YS-3 and
      its algicide represent promising candidates for use in HAB control. 

PMID- 26224454
TI  - Characterization of MocR, a GntR-like transcriptional regulator, in
      Bradyrhizobium japonicum: its impact on motility, biofilm formation, and soybean
      nodulation.
AB  - Bradyrhizobium japonicum is a Gram-negative soil bacterium that can fix nitrogen
      into ammonia by developing a symbiotic relationship with the soybean plant. MocR
      proteins make up a subfamily of GntR superfamily, one of the most widely
      distributed and prolific groups of the helix-turn-helix transcription factors. In
      this study, we constructed a mutant strain for mocR (blr6977) to investigate its
      role in cellular processes and symbiosis in B. japonicum. Although growth rate
      and morphology of the mutant were indistinguishable from those of the wild type,
      the mutant showed significant differences in motility and attachment (i.e.,
      biofilm formation) from the wild type. The mutant displayed a decrease in biofilm
      formation, but was more motile than the wild type. The inactivation of mocR did
      not affect the number of nodules on soybean roots, but caused delayed nodulation.
      Delayed nodulation intrigued us to study competitiveness of the mutant infecting
      soybeans. The mutant was less competitive than the wild type, indicating that
      delayed nodulation might be due to competitiveness. Gene expressions of other
      MocR subfamily members were also compared between the wild type and mutant
      strains. None of the mocR-like genes examined in this study were differentially
      expressed between both strains. 

PMID- 26224455
TI  - Role of the extracytoplasmic function sigma factor CarQ in oxidative response of
      Bradyrhizobium japonicum.
AB  - As a nitrogen-fixing bacterium, Bradyrhizobium japonicum can establish a
      symbiotic relationship with the soybean plant (Glycine max). To be a successful
      symbiont, B. japonicum must deal with plant defense responses, such as an
      oxidative burst. Our previous functional genomics study showed that carQ
      (bll1028) encoding extracytoplasmic function (ECF) sigma factor was highly
      expressed (107.8-fold induction) under oxidative stress. Little is known about
      the underlying mechanisms of how CarQ responds to oxidative stress. In this
      study, a carQ knock-out mutant was constructed using site-specific mutagenesis to
      identify the role of carQ in the oxidative response of B. japonicum. The carQ
      mutant showed a longer generation time than the wild type and exhibited
      significantly decreased survival at 10 mM H(2)O(2) for 10 min of exposure.
      Surprisingly, there was no significant difference in expression of oxidative
      stress-responsive genes such as katG and sod between the wild type and carQ
      mutant. The mutant also showed a significant increase in susceptibility to
      H(2)O(2) compared to the wild type in the zone inhibition assay. Nodulation
      phenotypes of the carQ mutant were distinguishable compared to those of the wild
      type, including lower numbers of nodules, decreased nodule dry weight, decreased
      plant dry weight, and a lower nitrogen fixation capability. Moreover, desiccation
      of mutant cells also resulted in significantly lower percent of survival in both
      early (after 4 h) and late (after 24 h) desiccation periods. Taken together, this
      information will provide an insight into the role of the ECF sigma factor in B.
      japonicum to deal with a plant-derived oxidative burst.

PMID- 26224456
TI  - Functional properties of the major outer membrane protein in Stenotrophomonas
      maltophilia.
AB  - Stenotrophomonas maltophilia is an opportunistic pathogen that is closely
      associated with high morbidity and mortality in debilitated and immunocompromised
      individuals. Therefore, to investigate the pathogenesis mechanism is urgently
      required. However, there are very few studies to evaluate the functional
      properties of outer membrane protein, which may contribute to the pathogenesis in
      S. maltophilia. In this study, three abundant proteins in the outer membrane
      fraction of S. maltophilia were identified by liquid chromatography-tandem mass
      spectrometry as OmpW1, MopB, and a hypothetical protein. MopB, a member of the
      OmpA family, was firstly chosen for functional investigation in this study
      because many OmpA-family proteins are known to be involved in pathogenesis and
      offer potential as vaccines. Membrane fractionation analyses demonstrated that
      MopB was indeed the most abundant outer membrane protein (OMP) in S. maltophilia.
      For functional studies, the mopB mutant of S. maltophilia (SmMopB) was
      constructed by insertional mutation. MopB deficiency resulted in a change in the
      protein composition of OMPs and altered the architecture of the outer membrane.
      The SmMopB strain exhibited reduced cytotoxicity toward L929 fibroblasts and was
      more sensitive to numerous stresses, including human serum, sodium dodecyl
      sulfate, and hydrogen peroxide compared with wildtype S. maltophilia. These
      results suggest that MopB may be a good candidate for the design of vaccines or
      anti-MopB drugs for controlling serious nosocomial infections of multidrug
      resistant S. maltophilia, especially in immunosuppressed patients. 

PMID- 26224457
TI  - The role of programmed death ligand 1 pathway in persistent biomaterial
      associated infections.
AB  - Staphylococcus epidermidis is commonly involved in biomaterial-associated
      infections. Bacterial small colony variants (SCV) seem to be well adapted to
      persist intracellularly in professional phagocytes evading the host immune
      response. We studied the expression of PD-L1/L2 on macrophages infected with
      clinical isolates of S. epidermidis SCV and their parent wild type (WT) strains.
      The cytokine pattern which is triggered by the examined strains was also
      analysed. In the study, we infected macrophages with S. epidermidis WT and SCV
      strains. Persistence and release from macrophages were monitored via lysostaphin
      protection assays. Moreover, the effect of IFN-gamma pre-treatment on bacterial
      internalisation was investigated. Expression of PD-L1/L2 molecules was analysed
      with the use of FACS. Inflammatory reaction was measured by IL-10, TNF-alpha
      ELISAs, and transcriptional induction of TNF-alpha. Our study revealed that
      clinical SCV isolates were able to persist and survive in macrophages for at
      least 3 days with a low cytotoxic effect and a reduced proinflammatory response
      as compared to WT strains. Bacteria upregulated PD-L1/L2 expression on
      macrophages as compared to non-stimulated cells. The results demonstrated that
      the ability of S. epidermidis SCVs to induce elevated levels of anti-inflammatory
      cytokine, IL-10, and reduced transcriptional induction of TNF-alpha, together
      with expression of PD-L1 on macrophages and the ability to persist
      intracellularly without damaging the host cell could be the key factor
      contributing to chronicity of SCV infections. 

PMID- 26224458
TI  - Antagonistic effect of peptidoglycan of Streptococcus sanguinis on
      lipopolysaccharide of major periodontal pathogens.
AB  - Streptococcus sanguinis is often found in subgingival biofilm including
      periodontopathogens, and is correlated with a delay in colonization by
      periodontopathogens. However, the effect of S. sanguinis on inflammation induced
      by periodontopathogens is poorly understood. Thus, this study investigated the
      effect of S. sanguinis peptidoglycan (PGN) on induction of TNF-alpha, IL-6, and
      IL-8 expression by lipopolysaccharide (LPS) of periodontal pathogens. LPS was
      extracted from Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis,
      and Tannerella forsythia, and PGN was isolated from S. sanguinis. THP-1 cells, a
      monocytic cell-line, were cotreated with LPS of the periodontal pathogens and S.
      sanguinis PGN, and then the expression of inflammatory cytokines was analyzed by
      real-time RT-PCR. To analyze the underlying mechanism, the binding assay of the
      LPS to CD14 or LPS-binding protein (LBP) was performed in the presence or absence
      of the PGN after coating recombinant human CD14 and LBP on EIA plate. The PGN
      inhibited the binding of LPS to CD14 and LBP in a dose-dependent manner. Also,
      THP-1 cells were co-treated with the LPS in the presence of N-acetylmuramic acid
      and N-acetylglucosamine, as components of PGN, and the competition binding assay
      to CD14 and LBP was performed. N-acetylmuramic acid inhibited the induction of
      inflammatory cytokine expression by LPS and the binding of LPS to CD14 or LBP
      whereas N-acetylglucosamine did not show such effect. Collectively, the results
      suggest that S. sanguinis PGN inhibited the cytokine expression induced by the
      LPS of periodontopathogens due to the inhibition of LPS binding to LBP and CD14.
      N-acetylmuramic acid of PGN may play a role in inhibition of the LPS binding of
      periodontopathogens to CD14 and LBP. 

PMID- 26224459
TI  - Requirement of the N-terminal residues of human cytomegalovirus UL112-113
      proteins for viral growth and oriLyt-dependent DNA replication.
AB  - The UL112-113 region of the human cytomegalovirus (HCMV) genome encodes four
      phosphoproteins of 34, 43, 50, and 84 kDa that promote viral DNA replication. Co
      transfection assays have demonstrated that self-interaction of these proteins via
      the shared N-termini is necessary for their intranuclear distribution as foci and
      for the efficient relocation of a viral DNA polymerase processivity factor (UL44)
      to the viral replication sites. However, the requirement of UL112-113 N-terminal
      residues for viral growth and DNA replication has not been fully elucidated.
      Here, we investigated the effect of deletion of the N-terminal regions of UL112
      113 proteins on viral growth and oriLyt-dependent DNA replication. A deletion of
      the entire UL112 region or the region encoding the 25 N-terminal amino-acid
      residues from the HCMV (Towne strain) bacmid impaired viral growth in bacmid
      transfected human fibroblast cells, indicating their requirement for viral
      growth. In co-immunoprecipitation assays using the genomic gene expressing the
      four UL112-113 proteins together, the 25 N-terminal amino-acid residues were
      found to be necessary for stable expression of UL112-113 proteins and their self
      interaction. These residues were also required for efficient binding to and
      relocation of UL44, but not for interaction with IE2, an origin-binding
      transcription factor. In co-transfection/replication assays, replication of the
      oriLyt-containing plasmid was promoted by expression of intact UL112-113
      proteins, but not by the expression of 25-amino-acid residue-deleted proteins.
      Our results demonstrate that the 25 N-terminal amino-acid residues of UL112-113
      proteins that mediate self-interaction contribute to viral growth by promoting
      their binding to UL44 and the initiation of oriLyt-dependent DNA replication. 

PMID- 26224461
TI  - [Intrathecal Baclofen Therapy for Cerebral Palsy].

PMID- 26224460
TI  - Molecular characterization of mammalian-adapted Korean-type avian H9N2 virus and
      evaluation of its virulence in mice.
AB  - Avian influenza A virus (AIV) is commonly isolated from domestic poultry and wild
      migratory birds, and the H9N2 subtype is the most prevalent and the major cause
      of severe disease in poultry in Korea. In addition to the veterinary concerns
      regarding the H9N2 subtype, it is also considered to be the next potential human
      pandemic strain due to its rapid evolution and interspecies transmission. In this
      study, we utilize serial lung-to-lung passage of a low pathogenic avian influenza
      virus (LPAI) H9N2 (A/Ck/Korea/163/04, WT163) (Y439-lineage) in mice to increase
      pathogenicity and investigate the potential virulence marker. Mouse-adapted H9N2
      virus obtained high virulence (100% mortality) in mice after 98 serial passages.
      Sequence results show that the mouse adaptation (ma163) possesses several
      mutations within seven gene segments (PB2, PA, HA, NP, NA, M, and NS) relative to
      the wild-type strain. The HA gene showed the most mutations (at least 11) with
      one resulting in the loss of an N-glycosylation site (at amino acid 166).
      Moreover, reverse genetic studies established that an E627K substitution in PB2
      and the loss of the N-glycosylation site in the HA protein (aa166) are critical
      virulence markers in the mouse-adapted H9N2 virus. Thus, these results add to the
      increasing body of mutational analysis data defining the function of the viral
      polymerase and HA genes and their roles in mammalian host adaptation. To our
      knowledge, this is first report of the generation of a mammalian-adapted Korea
      H9N2 virus (Y493-lineages). Therefore, this study offers valuable insights into
      the molecular evolution of the LPAI Korean H9N2 in a new host and adds to the
      current knowledge of the molecular markers associated with increased virulence. 

PMID- 26224462
TI  - [Molecular-Targeted Drug Therapy for Glioma Angiogenesis and Invasion].

PMID- 26224463
TI  - [Epidemiological Investigation of Patients in Persistent Vegetative States in
      Aomori, Japan].
AB  - The actual number and condition of Japanese patients in persistent vegetative
      states have not yet been fully understood. The aim of this study is to
      investigate the epidemiology of patients in persistent vegetative states in the
      Aomori prefecture. We sent questionnaires regarding gender, age, cause of
      persistent vegetative state, and residence of patient to all medical institutions
      in the Aomori prefecture (n=682). Two hundreds and seventeen institutions (31.8%)
      replied to the questionnaire, and eleven hundred ninety-eight
      patients(Male/Female=381/817) were included. Patients over 80 years-old were the
      most common (63.4%), and cerebrovascular stroke was the major cause (64.4%) of
      persistent vegetative state. Nursing homes (48.1%) and hospitals (34.6%) were the
      main care institutions. Population based analysis revealed that 869 persistent
      vegetative state patients per million were cared for in the Aomori prefecture.
      This result was twice as many as was previously reported in Miyagi prefecture.
      The number of patients in persistent vegetative states will increase in the
      future, due to an increasing elderly population and a high incidence of stroke in
      this demographic. We therefore predict that increased medical and administrative
      support will be required in the future.

PMID- 26224464
TI  - [Modified Technique for Primary Dural Closure in the Lateral Suboccipital
      Approach:Dural Moisturizing with Fibrin Glue Coating].
AB  - OBJECTIVE: When employing the lateral suboccipital approach, the thin dura
      shrinks due to the drying effect of illumination and air exposure, and dural
      substitutes are often needed for closure. We developed a new technique involving
      dural moisturizing with fibrin glue coating that facilitates primary dural
      closure. PATIENTS AND METHODS: We used this technique in 12 adults who underwent
      the lateral suboccipital approach for 5 hemifacial spasms, 3 trigeminal
      neuralgias, 2 cerebellopontine meningiomas, 1 vestibular schwannoma, and 1
      vertebral artery aneurysm. Fibrin glue was sprayed on the outer surface before
      opening the dura, and additionally sprayed on the inner surface of the reflected
      dural flap after opening the dura. After the intradural procedures the dura was
      closed with the usual knotted sutures. RESULTS: Dural closure was performed 65
      340 minutes (mean: 161.9 minutes) post-durotomy. This technique resulted in
      primary dural closure with a sufficient area of preserved dura in all but one
      patient. In this patient, the dura shrank due to coagulation of the dural
      attachment to the meningioma for which a small autologous substitute was
      required. There were no procedure-related complications such as cerebrospinal
      fluid leakage and meningitis. CONCLUSIONS: Dural moisturizing with fibrin glue
      coating is simple, protects the dura from drying and shrinkage, and facilitates
      primary dural closure in patients undergoing the lateral suboccipital approach.

PMID- 26224465
TI  - [A Case of Peripheral Middle Cerebral Artery Aneurysm Showing Repeated
      Morphological Changes].
AB  - We describe a case of a peripheral ruptured middle cerebral artery(MCA)aneurysm
      showing repeated morphological changes within a short period of 3 months. A 69
      year-old woman was admitted to her primary care hospital with headache. Cranial
      computed tomography (CT) showed subarachnoid hemorrhage (SAH), but ruptured
      aneurysm was not confirmed on 4-vessel cerebral angiography. Conservative
      treatment was provided in the form of pain relief and blood pressure control.
      However, left internal carotid artery angiography (ICAG) conducted 12 days post
      onset showed a peripheral MCA aneurysm, which was enlarged 1 week later. The
      patient did not tolerate balloon test occlusion, showing neurological deficit.
      Direct surgery was planned, but angiography on day 30 revealed a reduction in
      aneurysm size. Medical therapy was therefore continued for 1 month; however, the
      aneurysm showed repeated enlargements over 3 months. The patient therefore
      consulted our hospital for surgery, which was performed using a transsylvian
      approach. As we were unable to rule out pseudoaneurysm, we performed superficial
      temporal artery-MCA anastomosis as a form of trapping surgery. However, the
      lesion appeared to likely represent a congenital aneurysm when viewed
      macroscopically, so we performed neck clipping as a definitive treatment.
      Navigation and motor-evoked potential monitoring were useful to approach the
      aneurysm and predict the preservation of motor function. Histological examination
      revealed a congenital aneurysm with organized thrombus. The postoperative course
      was uneventful and the patient was discharged 2 weeks after surgery without any
      neurological deficit.

PMID- 26224466
TI  - [A Case of Traumatic Carotid Cavernous Fistula Treated with a Single Procedure
      Selective Transarterial Embolization Using Hydrogel Coils].
AB  - A 30-year-old man was admitted to our hospital after a bicycle accident.
      Proptosis, conjunctival congestion, and orbital vascular bruit appeared one month
      after the accident. Neuroradiological findings showed a traumatic carotid
      cavernous fistula(CCF). CCF is a pathologic arteriovenous shunt between the
      carotid artery and cavernous sinus. A detachable balloon was the standard device
      used for treatment of high flow direct CCF, although it is currently unavailable
      in Japan. Therefore, many other constructive strategies are being developed. We
      successfully treated this patient with single transarterial embolization using
      hydrogel coils. Hydrogel coils are platinum coils coated with polymeric water
      gels, and can be used at a prospect of delayed volume expansion. In our case, the
      patency of the internal carotid artery was maintained using the coils, and the
      symptoms improved shortly after the procedure. The use of hydrogel coils for the
      treatment of CCF appears to be safe and effective. 

PMID- 26224467
TI  - [A Case of Subgaleal Hematoma with Exophthalmos and Diplopia].
AB  - A 9-year-old girl struck the left side of her head on a doorknob, after which she
      gradually developed swelling. She was treated conservatively at another hospital
      before being referred and admitted to our hospital 9 days after injury, with
      complaints of exophthalmos and diplopia. Computed tomography (CT) scanning and
      magnetic resonance imaging (MRI) revealed a subgaleal hematoma (SGH). We
      therefore attempted to treat the patient by aspiration of the hematoma via needle
      puncture through the skin, for which we wrapped an elastic band around the head
      while infusing a hemostatic agent. No vascular anomalies and no abnormal shunts
      were identified by angiography under general anesthesia 13 days after injury. The
      patient was treated surgically due to increased head swelling and deteriorated
      exophthalmos. The liquefied, dark-red SGH was aspirated via a few cm of skin and
      a galeal incision on the left side of her head. A multiperforated drainage
      catheter was introduced into the hematoma cavity and the drainage catheter was
      connected to the vacuum-drain pump. After the surgery, the left exophthalmos
      disappeared. Twenty-three days after injury, she was discharged from our hospital
      without any neurological deficits.

PMID- 26224468
TI  - [A Case of Foix-Alajouanine Syndrome due to Perimedullary AVF: Remission and
      Aggravation Mechanism Considered by an Open Surgical Biopsy and Intraoperative
      ICG Angiography].
AB  - Foix-Alajouanine syndrome (FAS), also known as congestive myelopathy due to
      spinal vascular malformations, presents with paraplegia, sensory disturbance of
      lower limbs, and dysfunction of the bladder and rectum. Although FAS is
      characterized by a subacute onset of neurological symptoms that may wax and wane
      over a few years, the progression mechanism remains unclear. We report a case of
      FAS due to an angiographically occult arteriovenous fistula (AVF) that was
      diagnosed by an open surgical biopsy and intraoperative indocyanine green (ICG)
      angiography. The patient was a 74-year-old female who presented with a one-year
      history of gradually progressive gait disturbance, weakness, and decreased
      sensation in her legs associated with bladder and rectum dysfunction. MRI showed
      intramedullary T1 hypointensity, T2 hyperintensity at level Th4-12, and
      intramedullary enhancing with a Gd-DTPA lesion at level Th8-12. A true-FISP image
      of the MRI revealed an abnormal tortuous vessel in the dorsal spinal subarachnoid
      space, but digital subtraction angiography of the spine at the C1-L5 level showed
      no abnormality. The patient also underwent Th8-12 laminectomy for open biopsy.
      ICG angiography revealed blood flow stagnation in an abnormally enlarged
      posterior spinal vein. Histological findings indicated necrotizing myelopathy and
      stenosis with wall thickening of the posterior spinal vein. We hypothesized that
      the progression mechanism in the present case may have resulted from histological
      changes in the draining veins of an AVF. Intraoperative ICG angiography may be a
      valuable method, not only for diagnosing AVFs but also for determining the
      existence and pathological characteristics of FAS.

PMID- 26224469
TI  - [Drainage of the Frontal Sinus to Cure Epidural and Brain Abscesses Developed
      after Surgery via Anterior Interhemispheric Approach].
AB  - We report a woman whose anterior communicating artery (AcomA) aneurysm was
      clipped via an anterior interhemispheric approach when she was 49 years old. At
      the age of 51, she presented with a subcutaneous abscess and osteomyelitis, so
      the cranioplastic bone was removed. Six months later, she underwent cranioplasty
      using hydroxyapatite. Her subcutaneous abscess recurred and the epidural abscess
      and hydroxyapatite were removed 11 years later after the first operation. The
      patient underwent observation therapy for the next 4 years, as the dura was
      ossified. She presented with frontal swelling 15 years after aneurysmal clipping,
      and neither abscess puncture nor the administration of antibacterial drugs was
      curative. The patient also complained of chill, thirst, and tremor, and developed
      disorientation 25 days later. Computed tomography (CT) and magnetic resonance
      imaging (MRI) showed extension of the epidural and subcutaneous abscesses to a
      frontal brain abscess. After consulting an otolaryngologist, we performed frontal
      drainage into the nasal cavity. After making a bicoronal skin incision, the
      subcutaneous, epidural, and intracapsular brain abscesses were removed while
      taking care not to damage the capsules. A silicone T-tube was placed in the
      bifrontal epidural cavity (previous frontal sinus), and its tip was inserted into
      the nasal cavity through the nasofrontal duct for abscess drainage. After 3
      months, the tube was removed. A CT scan acquired 10 years later showed no brain
      abscess, perifocal edema, or epidural and subcutaneous abscesses.

PMID- 26224470
TI  - [A Case of Symptomatic Cyst Formation after BCNU Wafer Implantation for
      Glioblastoma].
AB  - We report a case of a 56-year-old woman admitted to our hospital for status
      epilepticus. Three months before hospitalization, the patient underwent gross
      total removal of a glioblastoma with BCNU wafer implantation in the left parietal
      lobe. The cavity was subsequently lined with five BCNU wafers. After admission,
      magnetic resonance imaging(MRI)showed cyst formation accompanied by strong edema,
      with no recurrence of glioblastoma. She was initially administered antiepileptic
      drugs and glycerol with betamethasone, after which her seizures stopped but
      recurred one month later due to a decrease in betamethasone. The BCNU wafers were
      removed four months after the initial surgery, after which the seizures
      completely stopped. Histopathological examination of the cavity indicated the
      presence of inflamed tissue and no recurrence of glioblastoma. Neurosurgeons
      should be aware of the possibility of cyst formation after BCNU wafer
      implantation for malignant gliomas. In this manuscript, we provide a case
      presentation and a review of the literature. 

PMID- 26224471
TI  - [A Case of Cavernous Sinus Dural Arteriovenous Fistula after Transverse-Sigmoid
      Sinus Dural Arteriovenous Fistula Treatment with Radical Transvenous Coil
      Embolization].
AB  - PURPOSE: We report a case of cavernous sinus dural arteriovenous fistula (dAVF)
      that developed after the treatment of a transverse-sigmoid sinus dAVF using
      transvenous embolization (TVE). CASE PRESENTATION: A 72-year-old woman presented
      with headache and left-sided tinnitus. Angiography demonstrated the presence of a
      left transverse-sigmoid sinus dAVF. After TVE, the patient's symptoms completely
      disappeared. Three years later, she complained of left-sided tinnitus and
      diplopia, and angiography revealed the presence of a left cavernous sinus dAVF.
      We performed transvenous coil embolization, and the dAVF disappeared.
      CONCLUSIONS: TVE has been widely recognized as an effective treatment for dAVF.
      However, dAVF may develop at a different location after TVE in a few cases. A
      long-term follow-up is therefore recommended.

PMID- 26224472
TI  - A V-shaped polyaromatic amphiphile: solubilization of various nanocarbons in
      water and enhanced photostability.
AB  - Nanocarbons are synthetic carbon-rich compounds with polyaromatic frameworks that
      have lately attracted attention as emerging functional materials. However, their
      extreme hydrophobicity and aggregation peculiarity, besides their shape and size
      diversities, precluded their study in solution, especially in "green" water. More
      convenient and general solubilizing methods of nanocarbon frameworks are required
      by using non-covalent supramolecular interactions. Here we report a protocol for
      solubilizing a wide range of nanocarbons, that is, fullerenes (C60 , C70 , C84 ,
      and C120 ), polyarenes (tetracene, pentacene, perylene, coronene, and
      hexabenzocoronene), and carbon nanotubes (single-walled and multi-walled CNTs),
      in water through manual grinding with V-shaped polyaromatic amphiphiles. The
      obtained aqueous nanocomposites are composed of nanocarbons encircled by the
      polyaromatic frameworks of the amphiphiles through multiple aromatic-aromatic
      interactions. Notably, the encapsulated photosensitive nanocarbons, such as
      tetracene, pentacene, and fullerene dimer, exhibit unusual stability toward
      UV/Vis light. 

PMID- 26224473
TI  - Exhaled nitric oxide and carbon monoxide in lung transplanted patients.
AB  - BACKGROUND: Exhaled nitric oxide (eNO) and carbon monoxide (eCO) are markers of
      pulmonary inflammation associated with acute graft rejection and lung infections
      in lung transplant (LTX) recipients. Regarding eNO and eCO levels in LTX patients
      affected by bronchiolitis obliterans syndrome (BOS), published data are
      discordant. OBJECTIVES: We aim to evaluate eNO at multiple flows, alveolar
      concentration of nitric oxide (CalvNO), maximum conducting airway wall flux
      (J'awNO) and eCO levels in LTX patients to assess the potential role of these
      parameters in BOS evaluation. METHODS: Fractional exhaled nitric oxide (FeNO),
      CalvNO and J'awNO were analysed in 30 healthy subjects and 27 stable LTX patients
      (12 BOS patients). Pulmonary function tests were performed after eNO and eCO
      assessment. Receiver operating characteristic (ROC) curves were conducted to
      evaluate diagnostic accuracy for BOS of eNO parameters. RESULTS: LTX patients
      reported higher values of FeNO at flow rates of 50 (p < 0.01), 150 (p < 0.05),
      350 ml/s (p < 0.001), and CalvNO (p < 0.0001) than healthy controls. BOS patients
      showed higher FeNO at flow rates of 150 (p < 0.05) and 350 ml/s (p < 0.01) and
      CalvNO (p < 0.001) than non-BOS patients. CalvNO reported a remarkable diagnostic
      accuracy for BOS (AUC: 0.82). There were no significant differences of eCO levels
      between LTX patients and healthy controls. CONCLUSION: LTX patients affected by
      BOS showed higher levels of FeNO 150 and 350, and CalvNO than non-BOS LTX
      patients, probably due to chronic airway inflammation and fibrotic remodelling.
      CalvNO may be a potential biomarker of BOS in LTX patients.

PMID- 26224474
TI  - The role of stearoyl-coenzyme A desaturase 1 in clear cell renal cell carcinoma.
AB  - This study aimed to investigate the correlations of stearoyl-coenzyme A
      desaturase 1 (SCD-1) with clear cell renal cell carcinoma (ccRCC) severity and
      PI3K-AKT-mTOR signaling pathway. From 2004 to 2006, tumor tissue and normal
      pericarcinomatous tissue from ccRCC samples were collected from ccRCC patients at
      Renji Hospital of Shanghai Jiaotong University. The expression of SCD-1 in the
      collected ccRCC samples and four cell lines (A498, 769-P, 786-O, and CAKI) was
      detected by Western blot. The correlation between SCD-1 expression and ccRCC
      severity was also analyzed by immunohistochemistry. Stable 786-O and 769-P ccRCC
      cells expressing SCD-1 short hairpin RNA (shRNA) were constructed, and the
      expression of proteins in the PI3K-AKT-mTOR signaling pathway was also detected.
      Finally, the inhibitory effect of PI3K-AKT-mTOR inhibitors (PI103, MK2206,
      rapamycin, AZD8055, and RAD001) on ccRCC cells stably expressing SCD-1 shRNA was
      also measured. Higher SCD-1 expression level was observed in ccRCC tissues
      compared with normal tissues. SCD-1 expression level was the highest in 786-O.
      SCD-1 expression was positively correlated with the tumor-node-metastasis (TNM)
      stage, grade of tumor cells, and lymphatic metastasis. There were no changes in
      the expression of AKT, ERK, PI3K, and PDK1. Significant differences were observed
      in the expression of p-AKT (at the Ser473 and Thr308 site), p-ERK, and two mTOR
      downstream molecules (4E-BP1 and p-P70S6K1) in cells stably expressing SCD-1
      shRNA. PI103 and AZD8055 could enhance the inhibitory effect of SCD-1
      interference on proliferation and migration of 786-O and 769-P cells. AZD8055 is
      recommended for the combined ccRCC treatment with shRNA interference. 

PMID- 26224475
TI  - Serum miR-483-5p: a novel diagnostic and prognostic biomarker for patients with
      oral squamous cell carcinoma.
AB  - Deregulation of microRNAs (miRNAs) is essential to tumor development, and serum
      miRNA profiles have been reported in several cancers. However, the serum miRNA
      profile in oral squamous cell carcinoma (OSCC) remained unclear. The present
      study aimed to explore abnormal miRNA profile in sera samples from OSCC patients
      and the association of miR-483-5p with patient prognosis. Microarray analysis was
      performed in sera from OSCC patients versus healthy controls. miR-483-5p
      expression was measured by reverse transcription (RT)-PCR and correlated to
      clinicopathological characteristics of OSCC patients. The prognostic significance
      was then evaluated with a Kaplan-Meier curve and log-rank tests, using a Cox
      proportional hazard model. According to microRNA array, 16 miRNAs were
      upregulated and 10 were downregulated in OSCC patient sera. miR-483-5p expression
      was significantly increased in OSCC patients (3.23-fold, p < 0.01), and this was
      significantly correlated with tumor nodal metastasis (TNM) stage and lymph nodal
      metastases (p < 0.01, p < 0.01). For predicting OSCC, receiver operating
      characteristic (ROC)/area under the curve (AUC) analysis confirmed a AUC of 0.85
      (sensitivity of 0.853 and specificity of 0.746). OSCC patients with high serum
      miR-483-5p had lower survival than those with low expression, and multivariate
      analyses for overall survival revealed that high serum miR-483-5p expression was
      an independent prognostic factor for OSCC (HR = 2.32, 95 %CI 1.20-4.48). miR-483
      5p expression increased in OSCC patient sera, and this may be a novel diagnostic
      and prognostic biomarker for OSCC. 

PMID- 26224477
TI  - MiR-375 targets KLF4 and impacts the proliferation of colorectal carcinoma.
AB  - MiR-375 has been identified as oncogenes or tumor suppressor genes which has the
      potential to the development and growth of cancers. However, the limited
      information concerning the expression and role of miR-375 in colorectal cancer
      (CRC) is available. In this work, we provide evidence for a function of miR-375
      in the inhibition of CRC proliferation. Here, we showed that miR-375, down
      modulated in human colorectal cancer tissues compared with normal human colon
      tissues, including several colorectal cancer cell lines. Subsequently, using the
      luciferase reporter assays, we found that the KLF4 untranslated region (3'UTR)
      carries the direct binding site of miR-375. In terms of function in vitro, CCK-8
      assay, colony formation assay, and cell cycle assay demonstrated that the
      overexpression of miR-375 suppressed CRC cell proliferation. Inhibition of KLF4
      performed similar effects with miR-375 overexpression on CRC cells, and
      overexpression of KLF4 could significantly reverse the tumor suppressive effects
      of miR-375 on CRC cells. Furthermore, we found overexpressed miR-375 effectively
      repressed tumor growth via KLF4 in xenograft animal experiment. Taken together,
      these results illustrated that miR-375 depresses proliferation of CRC through
      regulating 3'UTR of KLF4 mRNA, which might be a promising therapeutic target for
      treating colorectal cancers. 

PMID- 26224476
TI  - Prognostic significance of human tissue kallikrein-related peptidases 11 and 15
      in gastric cancer.
AB  - Human tissue kallikrein-related peptidases (KLK) are a group of 15 serine
      proteases which have been investigated as potential cancer biomarkers. This study
      determined the prognostic significance of KLK 11 and 15 expression levels in
      gastric carcinoma specimens. Expression of KLK11 and KLK15 was assessed by
      immunohistochemistry staining on a tissue microarray constructed from 113
      gastrectomy specimens from patients with gastric carcinoma. To minimize inter
      observer variability, expression levels were quantified using an automated
      algorithm. Epithelial and stromal staining were assessed separately. Both KLK11
      and KLK15 were expressed in gastric carcinoma. There was no significant
      correlation between either KLK11 or KLK15 expression and the presence of lymph
      node metastases or Lauren classification (intestinal vs. diffuse). Higher levels
      of KLK11 expression in gastric carcinoma were associated with significantly worse
      overall survival (p = 0.008), and a multivariate analysis showed that it had
      prognostic value independent of tumor stage and differentiation (p = 0.004).
      Variations in KLK15 expression were not significantly associated with prognosis.
      KLK11 shows promise as a potential independent prognostic marker for gastric
      carcinoma. 

PMID- 26224478
TI  - Transforming growth factor-beta signaling pathway cross-talking with ERalpha
      signaling pathway on regulating the growth of uterine leiomyoma activated by
      phenolic environmental estrogens in vitro.
AB  - The aim of this paper is to study the participation of transforming growth factor
      beta (TGF-beta) signaling pathway in mediating the growth of human uterine
      leiomyoma (UL) activated by phenolic environmental estrogens (EEs), via the
      interaction between TGF-beta and ER signaling pathways. The UL cells were
      prepared by primary culture and subculture methods. To validate the role of TGF
      beta3 (5 ng/ml) for the viability of human uterine leiomyoma cells, CCK-8 assay
      was performed in each of five treatment groups including E2 group (E2 10(9)
      mol/l), BPA group (bisphenol A 10 MUmol/l), NP group (nonylphenol 32 MUmol/l), OP
      group (octylphenol 8 MUmol/l), or control group (DMSO only). Subsequently, qRT
      PCR was applied to detect mRNA expressions of ERalpha and c-fos, while western
      blot assay was used to test the expressions of p-Smad3, SnoN, and c-fos proteins
      in all settings mentioned above; the expressions were compared among different
      groups, and also in settings with and without synchronous treatment of ICI
      182,780. Primarily cultured UL cells were successfully established. Compared with
      the control group, there were statistically significant increases in the
      proliferation rate of the UL cells in all EE groups or treated with TGF-beta3
      only (p < 0.05). Nevertheless, a slight decrease in proliferation rate of UL was
      detected in coexistence with TGF-beta3 in all EE groups (p > 0.05).
      Interestingly, mRNA expressions of ERalpha and c-fos reduced in the setting of
      coexistence of TGF-beta3 and EEs compared to isolated EE treatment (p < 0.05).
      Compared with the control group, the expression of p-Smad3 and c-fos proteins
      significantly decreased (p < 0.05) in each of E2, BPA, NP, and OP group, and the
      expression of SnoN protein also significantly reduced only in BPA and NP groups
      (p < 0.05), followed by TGF-beta3 treatment. When adding ICI 182,780, the
      expression of p-Smad3 protein significantly increased in OP group (p < 0.05), but
      slightly increased in E2, BPA, NP, and OP groups (p > 0.05). However, compared
      with the control group, the expressions of SnoN and c-fos proteins significantly
      decreased (p < 0.05) after adding ICI182,780. Moreover, there was a significant
      statistical difference in the expression of p-Smad3, SnoN, and c-fos proteins
      between pre- and post-treatment of ICI 182,780 in all groups (p < 0.05). The
      ERalpha signaling pathway and TGF-beta signaling pathway have different roles in
      the control of UL cell proliferation. The phenolic EEs can be a promoter of UL
      cell proliferation, which is mediated by ERalpha signaling pathway and its cross
      talking with TGF-beta signaling pathway. Both less exposure to EEs and blockade
      of TGF signaling pathway are necessary strategies to prevent UL. 

PMID- 26224479
TI  - Down-regulation of Sphk2 suppresses bladder cancer progression.
AB  - Bladder cancer is the second most common urological malignancy around the world
      and is by far the most frequent urological malignancy in China. The abnormal
      expression of sphingosine kinase 2 (SphK2) is associated with tumor progression
      and a poor patient survival rate, however, the effect of SphK2 on the bladder
      cancer cells remains unclear. The aim of the paper was to study the expression of
      SphK2 in bladder cancer and the role of SphK2 on the cell proliferation,
      metastasis, and apoptosis in bladder cancer in vitro. Our results showed that
      SphK2 is up-regulated in bladder cancer tissues compared with the corresponding
      adjacent non-neoplastic tissues, and the expression level of SphK2 was
      significantly higher in human bladder cancer cells in comparison with normal
      bladder epithelial cells. Silencing of SphK2 could inhibit the proliferation
      ability of T24 cells in vitro. In addition, SphK2 knockdown could induce a
      significant increase in the number of apoptotic cells. Furthermore, the transwell
      assay also showed significant cell migration inhibition in SphK2 siRNA
      transfectant compared with cell lines transfected with NC. Thus, this study
      suggested that SphK2 inhibition may provide a promising treatment for bladder
      cancer patients. 

PMID- 26224480
TI  - Downregulation of microRNA-217 and microRNA-646 acts as potential predictor
      biomarkers in progression, metastasis, and unfavorable prognosis of human
      osteosarcoma.
AB  - Despite the progress in therapeutic targets, it remains dissatisfactory for most
      osteosarcoma patients with metastasis or recurrence osteosarcoma. Therefore, it
      is required to determine the involved mechanisms of osteosarcoma. The aim of this
      study was to investigate the expression level of MiR-217 and miR-646 and also
      their association with clinicopathological features in patients with
      osteosarcoma. Total RNA was purified from patients with osteosarcoma and
      noncancerous bone tissues, and then quantitative real-time PCR was applied to
      evaluate the expression level of microRNAs. Our result suggested that miR-217
      expression was remarkably deceased in osteosarcoma bone tissue when compared with
      noncancerous bone tissues (mean +/- SD 5.32 +/- 1.231, 2.01 +/- 0.78; P = 0.024)
      and miR-646 expression decreased in osteosarcoma bone tissue in comparison with
      normal tissues (mean +/- SD 4.56 +/- 1.45, 1.76 +/- 1.24; P = 0.041). Our
      findings indicated that decreased expression of MiR-217 and miR-646 was strongly
      correlated with high tumor, node, and metastasis (TNM) stage (P = 0.015, P =
      0.002) and large cancer diameter (P = 0.041, P = 0.053). Kaplan-Meier survival
      and log-rank analysis indicated that shorter overall survival was strongly linked
      to decreased expression of miR-217 and miR-646 (log-rank test P = 0.034, P =
      0.026). In terms of miR-217, multivariate Cox proportional hazards model analysis
      has showed that reduction of miR-217 expression (P = 0.001), TNM stage (P =
      0.046), and lymph node metastasis (P = 0.006) were independently linked to a
      short-time survival of patients. In terms of miR-646, low expression of miR-646
      (P = 0.021), TNM stage (P = 0.052), and tumor size (P = 0.043) were independently
      associated with poor survival of patients as prognostic factors. Our findings
      suggested that downregulation of MiR-217 and miR-646 was associated with
      progression of osteosarcoma. MiR-217 and miR-646 may play a key role in
      suppression of tumor in osteosarcoma and would be applied as a novel therapeutic
      agent. 

PMID- 26224481
TI  - PPARgamma ameliorated LPS induced inflammation of HEK cell line expressing both
      human Toll-like receptor 4 (TLR4) and MD2.
AB  - TLR4 is transmembrane pattern-recognition receptor that initiates signals in
      response to diverse pathogen-associated molecular patterns especially LPS.
      Recently, there have been an increasing number of studies about the role of TLRs
      in the pathogenesis of several disorders as well as the therapeutic potential of
      TLR intervention in such diseases. Peroxisome proliferator-activated receptor
      gamma (PPARgamma) is a ligand-activated transcription factor with numerous
      biological effects. PPARgamma has been shown to exert a potential anti
      inflammatory effect through suppression of TLR4-mediated inflammation. Therefore,
      PPARgamma agonists may have a potential to combat inflammatory conditions in
      pathologic states. The current study aims to show the decrease of inflammation by
      overexpression of PPARgamma in a cell reporter model. To reach this goal,
      recombinant pBudCE4.1 (+) containing encoding sequences of human TLR4 and MD2 was
      constructed and used to transfect HEK cells. Subsequently, inflammation was
      induced by LPS treatment as control group. In the treatment group, overexpression
      of PPARgamma prior to inflammation was performed and the expression of
      inflammatory markers was assessed in this condition. The expression of
      inflammatory markers (TNFalpha and iNOS) was defined by quantitative real time
      PCR and the amount of phosphorylated NF-kappaB was measured by western blot. Data
      indicated expression of TNFalpha and iNOS increased in LPS induced inflammation
      of stably transformed HEK cells with MD2 and TLR4. In this cell reporter model
      overexpression of PPARgamma dramatically prevented LPS-induced inflammation
      through the blocking of TLR4/NF-kappaB signaling. PPARgamma was shown to
      negatively regulate TLR4 activity and therefore exerts its anti-inflammatory
      action against LPS induced inflammation. 

PMID- 26224482
TI  - A comparative study on expression profile of developmentally important genes
      during pre-implantation stages in buffalo hand-made cloned embryos derived from
      adult fibroblasts and amniotic fluid derived stem cells.
AB  - Abnormal gene expression in somatic cell nuclear transfer embryos due to aberrant
      epigenetic modifications of the donor nucleus may account for much of the
      observed diminished viability and developmental abnormalities. The present study
      compared the developmentally important gene expression pattern at 4-cell, 8- to
      16-cell, morula, and blastocyst stages of buffalo nuclear transfer (NT) embryos
      from adult fibroblasts (AFs) and amniotic fluid stem cells (AFSCs). In vitro
      fertilized embryos were used as control embryos. Alterations in the expression
      pattern of genes implicated in transcription and pluripotency (OCT4, STAT3,
      NANOG), DNA methylation (DNMT1, DNMT3A), histone deacetylation (HDAC2), growth
      factor signaling, and imprinting (IGF2, IGF2R), apoptosis (BAX, BCL2), oxidative
      stress (MnSOD), metabolism (GLUT1) regulation were observed in cloned embryos.
      The expression of transcripts in AFSC-NT embryos more closely followed that of
      the in vitro fertilized embryos compared with AF-NT embryos. It is concluded that
      AFSCs with a relatively undifferentiated genome may serve as suitable donors
      which could be reprogrammed more efficiently to reactivate expression of early
      embryonic genes in buffalo NT. 

PMID- 26224483
TI  - Assessment of ventricular function in adults with repaired Tetralogy of Fallot
      using myocardial deformation imaging.
AB  - AIMS: Many patients with repaired Tetralogy of Fallot (ToF) have right
      ventricular (RV) volume overload due to pulmonary regurgitation (PR). We studied
      the effect of volume overload on global and regional RV and left ventricular (LV)
      deformation, and their relationships with conventional diagnostic parameters.
      METHODS AND RESULTS: In this cross-sectional study, 94 prospectively recruited
      ToF patients (61% male, age 32.8 +/- 9.5 years, age at repair 1.9 [0.8-5.7]
      years, 39% pulmonary homograft) and 85 healthy controls of similar age and sex
      underwent echocardiography and electrocardiography. In a subset of patients,
      cardiac magnetic resonance imaging, bicycle ergometry, and NT-proBNP measurement
      were performed within the same day. With speckle-tracking echocardiography, we
      analysed peak systolic global longitudinal strain (GLS), segmental longitudinal
      strain and strain rate of the RV free wall, LV lateral wall, and septum. Patients
      had a lower RV free wall strain than controls (-18.1 +/- 4.5 vs. -26.5 +/- 4.5%,
      P < 0.001), especially at the apical segment (-15.9 +/- 7.4 vs. -28.2 +/- 7.7%, P
      < 0.001), and lower RV strain rate. LV GLS was also lower (-17.4 +/- 2.5 vs. 
      19.6 +/- 1.9%, P < 0.001), mainly due to the interventricular septum. Patients
      with PR >25% had higher LV GLS and RV free wall strain than patients with PR
      <=25% (P = 0.004, P = 0.039, respectively). No relationships were found with NT
      proBNP or exercise capacity. CONCLUSION: RV free wall strain and strain rate are
      decreased in adults late after ToF repair, especially at the apical segment
      suggesting that apical function is most affected in these RVs. Regarding the LV,
      septal strain is decreased indicating that RV dysfunction adversely affects LV
      function, probably by mechanical coupling of the ventricles.

PMID- 26224484
TI  - A comparative study of thermo-sensitive hydrogels with water-insoluble paclitaxel
      in molecule, nanocrystal and microcrystal dispersions.
AB  - In situ thermo-sensitive hydrogels have attracted increasing attention for
      alternative cancer therapies due to their long-term and effective drug levels at
      local sites. Besides synthesizing new thermo-sensitive polymers, we can also
      fabricate this delivery system by combining a hydrogel with a thermo-response and
      drug in a different dispersion state, such as drug nanocrystals. However, the
      impact of the drug dispersion state or dimension on the quality of such a local
      injectable system is still unknown. So, here we developed and compared three
      types of F127 hydrogel systems with either paclitaxel or the near infra-red probe
      DiR in molecules (MOs), nanocrystals (NCs) and microcrystals (MCs), respectively.
      With 120 nm rod-shape nanocrystals, the NCs-Gel achieved a high drug loading,
      moderate drug release rate and gel erosion in vitro and in vivo, medium
      intratumoral drug residue but the best anti-tumor efficacy in 4T1 tumor bearing
      BALB/c mice. With the free drug solubilized in 20 nm micelles of the gel, the MOs
      Gel system demonstrated the least drug loading and the fastest drug release and
      gel erosion, leading to the least intratumoral residue as well as the lowest anti
      tumor effect. Finally, when dispersed in micron-grade rod-shape drug crystals,
      the MCs-Gel exhibited a high drug loading but poor stability, precipitating in
      vitro and in vivo, the highest intratumoral residue but the least drug release,
      resulting in moderate tumor inhibition. In conclusion, this study clarifies the
      effect of the drug dispersion state and scale on the behavior of a thermo
      sensitive hydrogel, indicating the advantage of the NCs-Gel system, and it
      provides a basis for the future design of the local delivery of hydrophobic anti
      cancer agents. 

PMID- 26224485
TI  - Compassion: hard to define, impossible to mandate.

PMID- 26224486
TI  - Comparison of phosphorylation patterns across eukaryotes by discriminative N-gram
      analysis.
AB  - BACKGROUND: How protein phosphorylation relates to kingdom/phylum divergence is
      largely unknown and the amino acid residues surrounding the phosphorylation site
      have profound importance on protein kinase-substrate interactions. Standard motif
      analysis is not adequate for large scale comparative analysis because each
      phophopeptide is assigned to a unique motif and perform poorly with the
      unbalanced nature of the input datasets. RESULTS: First the discriminative n
      grams of five species from five different kingdom/phyla were identified. A
      signature with 5540 discriminative n-grams that could be found in other species
      from the same kingdoms/phyla was created. Using a test data set, the ability of
      the signature to classify species in their corresponding kingdom/phylum was
      confirmed using classification methods. Lastly, ortholog proteins among proteins
      with n-grams were identified in order to determine to what degree was the
      identity of the detected n-grams a property of phosphosites rather than a
      consequence of species-specific or kingdom/phylum-specific protein inventory. The
      motifs were grouped in clusters of equal physico-chemical nature and their
      distribution was similar between species in the same kingdom/phylum while clear
      differences were found among species of different kingdom/phylum. For example,
      the animal-specific top discriminative n-grams contained many basic amino acids
      and the plant-specific motifs were mainly acidic. Secondary structure prediction
      methods show that the discriminative n-grams in the majority of the cases lack
      from a regular secondary structure as on average they had 88% of random coil
      compared to 66% found in the phosphoproteins they were derived from. CONCLUSIONS:
      The discriminative n-grams were able to classify organisms in their corresponding
      kingdom/phylum, they show different patterns among species of different
      kingdom/phylum and these regions can contribute to evolutionary divergence as
      they are in disordered regions that can evolve rapidly. The differences found
      possibly reflect group-specific differences in the kinomes of the different
      groups of species.

PMID- 26224488
TI  - TGF-beta1 inhibits the production of IFN in response to CpG DNA via
      ubiquitination of TNF receptor-associated factor (TRAF) 6.
AB  - The effect of TGF-beta1 on CpG DNA-induced type I IFN production was examined by
      reconstituting a series of signaling molecules in TLR 3 signaling. TGF-beta1
      inhibited CpG DNA-induced IFN-alpha4 productivity in HeLa cells. Transfection of
      IFN regulatory factor (IRF)7 but not TNF receptor-associated factor (TRAF)6 and
      TRAF3 into cells triggered IFN-alpha4 productivity, and TGF-beta1 inhibited IRF7
      mediated type I IFN production in the presence of TRAF6. TGF-beta1 induced
      ubiquitination of TRAF6, although CpG DNA did not induce it. Moreover, TGF-beta1
      accelerated the ubiquitination of TRAF6 in the presence of CpG DNA. TGF-beta1
      ubiquitinated TRAF6 at K63 but not K48. TGF-beta1 also induced ubiquitination of
      IRF7. Further, TGF-beta1 did not impair the interaction of IRF7 and TRAF6. CpG
      DNA induced the phosphorylation of IRF7 in the presence of TRAF6, whereas TGF
      beta1 inhibited the IRF7 phosphorylation. Blocking of TRAF6 ubiquitination
      abolished the inhibition of CpG DNA-induced type I IFN production by TGF-beta.
      Taken together, TGF-beta was suggested to inhibit CpG DNA-induced type I IFN
      production transcriptionally via ubiquitination of TRAF6. 

PMID- 26224487
TI  - Augmentation of autophagy by atorvastatin via Akt/mTOR pathway in spontaneously
      hypertensive rats.
AB  - Autophagy is activated in hypertension-induced cardiac hypertrophy. However, the
      mechanisms and significance of an activated autophagy are not clear. This study
      was designed to determine the role of atorvastatin (ATO) in cardiac autophagy and
      associated benefits on cardiac remodeling and left ventricular function in
      spontaneously hypertensive rats (SHRs). Twenty-eight male SHRs at 8 weeks of age
      were randomized to treatment with vehicle (saline solution; SHR+V) or ATO
      (SHR+ATO; 50 mg kg(-1) per day) for 6 or 12 months. Age-matched male Wistar-Kyoto
      (WKY) rats were used as normotensive controls. Cardiac magnetic resonance was
      used to evaluate cardiac function and structure. Compared with WKY rats, SHRs
      showed significant left ventricle (LV) dysfunction, remodeling and increases in
      cardiomyocyte size, which were all attenuated by 6 and 12 months of ATO
      treatment. Compared with WKY rats, autophagy was activated in the hearts of SHRs
      and this effect was amplified by chronic ATO treatment, particularly following 12
      months of treatment. Protein expression levels of microtubule-associated protein
      1 light chain 3-II and beclin-1, the biomarkers of an activated cardiac
      autophagy, were significantly elevated in ATO-treated versus vehicle-treated SHRs
      and control WKY rats. Cardiac Akt and phosphorylated mammalian target of
      rapamycin (mTOR) expression were also increased in the hearts of SHR versus WKY
      rats, and this effect was attenuated by ATO treatment. These findings suggest
      that ATO-mediated improvements in LV function and structure in SHRs may be, in
      part, through its regulation of cardiac autophagy via the Akt/mTOR pathway. 

PMID- 26224489
TI  - g-Engineering in Hybrid Rotaxanes To Create AB and AB2 Electron Spin Systems: EPR
      Spectroscopic Studies of Weak Interactions between Dissimilar Electron Spin
      Qubits.
AB  - Hybrid [2]rotaxanes and pseudorotaxanes are reported where the magnetic
      interaction between dissimilar spins is controlled to create AB and AB2 electron
      spin systems, allowing independent control of weakly interacting S=${{ 1/2 }}$
      centers. 

PMID- 26224490
TI  - Examination of virtual phantoms with respect to their possible use in assessing
      compliance with the electromagnetic field exposure limits specified by Directive
      2013/35/EU.
AB  - According to Directive 2013/35/EU, any assessment of hazards associated with
      exposure to electromagnetic fields (EMF) in the workplace needs an evaluation of
      quantities characterizing biophysical effects caused inside human bodies by
      exposure. Such quantities (induced electric field or specific energy absorption
      rate) may be evaluated by computer simulations in virtual models (phantoms),
      representing interaction between EMF and the worker's body with respect to
      modelling the EMF source, the structure of the working environment and the human
      body. The paper describes the effects of the properties of various virtual
      phantoms used in recently published studies on various aspects of EMF exposure
      with respect to their possible involvement in assessing occupational
      electromagnetic hazards as required by Directive 2013/35/ EU. The parameters of
      phantoms have been discussed with reference to: dimensions, posture, spatial
      resolution and electric contact with the ground. Such parameters should be
      considered and specified, and perhaps also standardized, in order to ensure that
      the numerical simulations yield reliable results in a compliance analysis against
      exposure limits or in an exposure assessment for EMF-related epidemiological
      studies. The outcomes of the presented examination of virtual phantoms used in
      numerical simulations show that they can be effectively used in the assessment of
      compliance with the exposure limits specified by Directive 2013/35/EU, but
      various other factors should be also considered, e.g., the relationship between
      phantom posture and a realistic exposure situation (flexible phantoms use),
      limited resolution preventing reliable evaluation of physical estimators of
      exposure, or a non-realistic area of phantom surface in contact with the ground. 

PMID- 26224491
TI  - Effects of real and simulated weightlessness on the cardiac and peripheral
      vascular functions of humans: A review.
AB  - Weightlessness is an extreme environment that can cause a series of adaptive
      changes in the human body. Findings from real and simulated weightlessness
      indicate altered cardiovascular functions, such as reduction in left ventricular
      (LV) mass, cardiac arrhythmia, reduced vascular tone and so on. These alterations
      induced by weightlessness are detrimental to the health, safety and working
      performance of the astronauts, therefore it is important to study the effects of
      weightlessness on the cardiovascular functions of humans. The cardiovascular
      functional alterations caused by weightlessness (including long-term spaceflight
      and simulated weightlessness) are briefly reviewed in terms of the cardiac and
      peripheral vascular functions. The alterations include: changes of shape and mass
      of the heart; cardiac function alterations; the cardiac arrhythmia; lower body
      vascular regulation and upper body vascular regulation. A series of conclusions
      are reported, some of which are analyzed, and a few potential directions are
      presented. 

PMID- 26224492
TI  - Endotoxin exposure and changes in short-term pulmonary function among sewage
      workers.
AB  - OBJECTIVES: The inhaled endotoxin is considered as a causative factor in the
      process of acute bronchial obstruction, which can be measured by a decrease in
      forced expiratory volume in 1 s (FEV1). The aim of this study was to assess
      endotoxin exposure among sewage treatment plant workers (STPW) and its effect on
      across-shift changes in respiratory airflow. MATERIAL AND METHODS: A group of 78
      STPW from a large sewage treatment plant was studied. Inhalable dust for
      endotoxin assessment was collected using personal aerosol samplers. Endotoxin was
      assayed with the kinetic, chromogenic Limulus amebocyte lysate test. Across-shift
      spirometric measurements were performed on Mondays, after 2-days absence from
      work, with the use of portable spirometer. The forced vital capacity (FVC), and
      FEV1 parameters were analyzed. Multifactor regression modeling was performed to
      determine parameters significantly associated with endotoxin exposure. RESULTS:
      The concentration of inhalable dust and endotoxin ranged from 0.01-1.38 mg/m3 and
      0.68-214 endotoxin units per cubic meter of air (EU/m3), respectively. Endotoxins
      were characterized with the skewed distribution (arithmetic mean (AM) = 38.8
      EU/m3, geometric mean (GM) = 15.4 EU/m3, geometric standard deviation (GSD) =
      4.21). Through the use of multifactor analysis, which excluded the main
      confounders (inhalable dust and smoking habit) it was found that, despite low
      levels of endotoxin, it had significant impact on the observed across-shift
      decline in FEV1 (p = 0.044). For this parameter, the regression slope was
      additionally calculated (r = -0.017, p = 0.071). CONCLUSIONS: Relatively low
      levels of endotoxin among sewage treatment plant workers may cause small, but
      significant across-shift declines in FEV1. The observed relationship was
      independent of organic dust concentrations and smoking habit. The respiratory
      protection should be provided for STPW.

PMID- 26224493
TI  - Assessment of exposure to fungi in the heavily contaminated work environment (a
      solid waste sorting plant) based on the ergosterol analysis.
AB  - OBJECTIVES: This paper reports on the results of the study aimed at application
      of ergosterol as an quantitative indicator of fungal bioaerosol present in the
      indoor air in occupational environment heavily contaminated with organic dust as
      well as its comparison with the culturable method. MATERIAL AND METHODS: The
      study was conducted in the indoor solid waste sorting plant. Using Andersen
      impactor adapted to 1 plate at the flow rate of 30 l/min, indoor air was sampled
      in the workers' breathing zone. Ergosterol was sampled using gelatinous filter
      (1000 l of air) and then analyzed by means of the spectrophotometric method.
      Fungi were sampled on malt extract agar (MEA) medium (3 replications: 2 l, 7.5 l,
      15 l of air) and analyzed by means of the culturable method. Based on ergosterol
      analyzes, concentration of fungi was calculated. Results were given as the range
      assuming min. as 5.1 pg ergosterol/spore and max as 1.7 pg ergosterol/spore.
      RESULTS: The average concentrations of ergosterol in a working room (arithmetic
      mean (AM), standard deviation (SD); minimum-maximum (min.-max)) were,
      respectively: 2.16, 0.72; 0.85-2.92 MUg/m3; fungi calculated based on ergosterol 
      424.1*103-1272.4*103, 140.1*103- 420.4*103, 167*103-1716.5*103 CFU/m3, and
      culturable fungi - 13*103, 9.7*103, 1.9*103-34*103 CFU/m3). It was revealed that
      concentrations of calculated fungi were even 2 orders of magnitude higher than
      culturable fungi. CONCLUSIONS: The quantitative assessment of moldiness by means
      of ergosterol measurement seems to be a reliable indicator for environments
      heavily contaminated with organic dust, where viable and non-viable fungi are
      present in high proportions. Based on that result, more restrictive (as compared
      to a similar assessment carried out by means of the culturable method) hygienic
      recommendations, especially those related to the use of preventive measures
      protecting the employees' respiratory tract, should have been undertaken.

PMID- 26224494
TI  - An approach to represent a combined exposure to air pollution.
AB  - OBJECTIVES: The objective of this study was to present a technique for estimating
      the effect of ambient air pollution mix on health outcomes. MATERIAL AND METHODS:
      We created a technique of indexing air pollution mix as a cause of the increased
      odds of health problems. As an illustrative example, we analyzed the impact of
      pollution on the frequency of emergency department (ED) visits due to colitis
      among young patients (age < 15 years, N = 11 110). Our technique involves 2
      steps. First, we considered 6 ambient air pollutants (carbon monoxide, nitrogen
      dioxide, sulphur dioxide, ozone, and 2 measures of particulate matter) treating
      each pollutant as a single exposure. Odds ratios (ORs) for ED visits associated
      with a standard increase (interquartile range - IQR) in the pollutants levels
      were calculated using the case-crossover technique. The ORs and their 95%
      confidence intervals (95% CIs) were also found for lagged exposures (for lags 1-9
      days). Second, we defined a Health Air Study Index (HASI) to represent the
      combined impact of the 6 air pollutants. RESULTS: We obtained positive and
      statistically significant results for individual air pollutants and among them
      the following estimations: OR = 1.06 (95% CI: 1.02-1.1, NO2 lag 3, IQR = 12.8
      ppb), OR = 1.04 (95% CI: 1.01-1.07, SO2 lag 4, IQR = 2.3 ppb), OR = 1.04 (95% CI:
      1-1.06, PM lag 3, IQR = 6.2 MUg/m3). Among the re-calculated ORs with the HASI
      values as an exposure, the highest estimated value was OR = 1.37 (95% CI: 1.12
      1.68, for 1 unit of the HASI, lag 3). CONCLUSIONS: The proposed index (HASI)
      allows to confirm the pattern of associations for lags obtained for individual
      air pollutants. In the presented example the used index (HASI) indicates the
      strongest relation with the exposure lagged by 3 days.

PMID- 26224495
TI  - Health risk to medical personnel of surgical smoke produced during laparoscopic
      surgery.
AB  - OBJECTIVES: During laparoscopic cholecystectomy, the removal of the gall bladder,
      pyrolysis occurs in the peritoneal cavity. Chemical substances which are formed
      during this process escape into the operating room through trocars in the form of
      surgical smoke. The aim of this study was to identify and quantitatively measure
      a number of selected chemical substances found in surgical smoke and to assess
      the risk they carry to medical personnel. MATERIAL AND METHODS: The study was
      performed at the Maria Sklodowska-Curie Memorial Provincial Specialist Hospital
      in Zgierz between 2011 and 2013. Air samples were collected in the operating room
      during laparoscopic cholecystectomy. RESULTS: A complete qualitative and
      quantitative analysis of the air samples showed a number of chemical substances
      present, such as aldehydes, benzene, toluene, ethylbenzene, xylene, ozone,
      dioxins and others. CONCLUSIONS: The concentrations of these substances were much
      lower than the hygienic standards allowed by the European Union Maximum
      Acceptable Concentration (MAC). The calculated risk of developing cancer as a
      result of exposure to surgical smoke during laparoscopic cholecystectomy is
      negligible. Yet it should be kept in mind that repeated exposure to a cocktail of
      these substances increases the possibility of developing adverse effects. Many of
      these compounds are toxic, and may possibly be carcinogenic, mutagenic or
      genotoxic. Therefore, it is necessary to remove surgical smoke from the operating
      room in order to protect medical personnel.

PMID- 26224496
TI  - Molecular profile of sensitization in subjects with short occupational exposure
      to latex.
AB  - OBJECTIVES: We examined the prevalence of latex allergy in subjects with
      occupational exposure to latex allergens for less than 5 years, determining the
      disease spectrum in symptomatic workers. We identified the most frequent
      molecular allergens by Immuno- CAP (ICAP), correlating the findings with skin
      prick test (SPT) results. MATERIAL AND METHODS: Seven hundred twenty-three
      healthcare students using latex gloves on a regular basis were invited to
      participate in a baseline questionnaire screening. An ICAP serum test was
      performed only when a possible latex allergy was indicated by the questionnaire.
      RESULTS: The total number of participants responding to the baseline survey was
      619. Glove-related symptoms were indicated by 4% (N = 25) of the students. The
      most common symptom was contact dermatitis (N = 18, 72%). In 12 subjects, ICAP
      revealed a real sensitization to latex, with a recombinant latex allergen profile
      showing a high frequency for rHev b 6.01 specific immunoglobulin E (sIgE) (N = 9,
      67%). In these individuals, skin symptoms were more prevalent than other types
      (88%). CONCLUSIONS: The combined positivity for rHev b 6.01, rHev 8 and rHev b 5
      determined by ICAP identified 92% of latex-allergic subjects with short-term
      exposure to latex.

PMID- 26224497
TI  - Occupational exposure to asbestos is associated with increased mortality in men
      recruited for a population-based study in Germany.
AB  - OBJECTIVES: Occupational exposure to asbestos is associated with increased
      mortality which, however, has not been thoroughly validated in a general
      population. We have aimed at exploring whether this association may be confirmed
      within a population-based setting after adjustment for confounders. Furthermore,
      the impact of tobacco consumption on the association between occupational
      exposure to asbestos and mortality is assessed. MATERIAL AND METHODS: We used
      data from 2072 (224 exposed) male participants of the Study of Health in
      Pomerania. Information on exposure to asbestos is based on a selfreport. Median
      follow-up time was 11.3 years. All-cause mortality and cause-specific mortality
      of exposed and non-exposed men were compared using mortality rate ratios, Kaplan
      Meier analyses and multivariable Cox regression. RESULTS: During the follow-up,
      52 (23.2%) exposed and 320 (17.3%) non-exposed participants deceased. Exposed
      subjects had increased hazard ratios (HR) for all-cause mortality (HR=1.48, 95%
      CI: 1.1-2), benign lung disease mortality (HR=3, 95% CI: 1.18- 7.62) and stomach
      cancer mortality (HR=4.59, 95% CI: 1.53-13.76). The duration of exposure (per 10
      years) was associated with all-cause (HR=1.21, 95% CI: 1.07-1.36) and benign lung
      disease mortality (HR=1.68, 95% CI: 1.26-2.22). Smokers occupationally exposed to
      asbestos had the highest risk for all-cause (HR=3.70, 95% CI: 2.19-6.27) and
      cancer mortality (HR=4.56, 95% CI: 1.99-10.48) as compared to non-asbestos
      exposed non-smokers. CONCLUSIONS: Our results confirm associations of
      occupational exposure to asbestos with all-cause, benign lung disease, and
      stomach cancer mortality and underline the impact of joint effects of asbestos
      and smoking on mortality.

PMID- 26224498
TI  - Post-exercise proteinuria in the cadets trained on Special Aerial Gymnastics
      Instruments.
AB  - OBJECTIVES: Assessment of the effect of training on Special Aerial Gymnastics
      Instruments (SAGI) on the urine beta-2- microglobulin (beta-2M), albumin (ALB),
      total protein (TP), N-acetyl-beta-D-glucosaminidase EC.3.2.1.30 (NAG), expressed
      as creatinine (Cr) and on the physical fitness of the examined cadets in
      comparison with the control group. MATERIAL AND METHODS: The study involved 55
      cadets aged 20, divided into group A (N = 41) trained on SAGI, and group B (N =
      14) - a control group. The urine was collected twice: before the training (BT)
      and after the training (AT) at the start (training I), during (training II), and
      after completion of the training program (training III). Urine proteins were
      assayed with commercially available kits. RESULTS: In group A, results obtained
      in trainings I, II and III showed a statistically significant increase in beta
      2M/Cr, NAG/Cr, TP/Cr, ALB/Cr indices in AT compared with the baseline BT values.
      Similarly in group B, a statistically significant increase in beta-2M/Cr, NAG/Cr
      (trainings I, II), TP/Cr, AT compared with the baseline BT values in trainings I,
      II, and III was noted. Comparison of both groups showed a higher value of the
      post-exercise proteinuria in group B than in group A. In group A, a significant
      correlation between TP/Cr vs. ALB/Cr, NAG/Cr vs. TP/Cr, beta-2M/Cr vs. TP/Cr,
      i.e., r = 0.62 at p < 0.001; r = 0.33 at p = 0.03; r = 0.60 at p < 0.001, and r =
      0.52 at p < 0.001, respectively, was observed in group A, training III, AT.
      CONCLUSIONS: Assayed urine proteins depend on the intensity of physical exercise,
      the type of exercise, and the level of physical fitness.

PMID- 26224499
TI  - Work locus of control and burnout in Polish physiotherapists: The mediating
      effect of coping styles.
AB  - OBJECTIVES: The aim of this study was to explain the relationship between work
      locus of control and burnout in Polish physiotherapists through the mediation of
      coping styles. In particular, we hypothesized that external work locus of control
      may have a positive direct relationship with burnout symptoms via positive
      relationship with emotion-focused and avoidant coping styles, and a negative
      relationship with problem-focused style. MATERIAL AND METHODS: We tested the
      mediational hypothesis using structural equation modeling of self-report data
      from 155 Polish physiotherapists. RESULTS: The relationship between external work
      locus of control and physiotherapists' burnout was shown to be mediated by a
      positive relationship with emotion-focused coping and an inverse relationship
      with problem-focused coping. The variables included in the model explained about
      15% of the variance of emotional exhaustion, 14% of depersonalization, and 14% of
      personal accomplishment. CONCLUSIONS: Physiotherapists perceiving the situation
      as difficult to control, feel more burned out when they use more emotion-focused
      strategies, and less problem-focused strategies. This indicates the importance of
      including both, problem-focused coping training and increasing the perception of
      the situation controllability in preventing physiotherapists' burnout programs.

PMID- 26224500
TI  - Protecting and promoting mental health of nurses in the hospital setting: Is it
      cost-effective from an employer's perspective?
AB  - OBJECTIVES: Nurses are at elevated risk of burnout, anxiety and depressive
      disorders, and may then become less productive. This begs the question if a
      preventive intervention in the work setting might be cost-saving from a business
      perspective. MATERIAL AND METHODS: A cost-benefit analysis was conducted to
      evaluate the balance between the costs of a preventive intervention among nurses
      at elevated risk of mental health complaints and the cost offsets stemming from
      improved productivity. This evaluation was conducted alongside a cluster
      randomized trial in a Dutch academic hospital. The control condition consisted of
      screening without feedback and unrestricted access to usual care (N = 206). In
      the experimental condition screen-positive nurses received personalized feedback
      and referral to the occupational physician (N = 207). RESULTS: Subtracting
      intervention costs from the cost offsets due to reduced absenteeism and
      presenteeism resulted in net-savings of 244 euros per nurse when only absenteeism
      is regarded, and 651 euros when presenteeism is also taken into account. This
      corresponds to a return-on-investment of 5 euros up to 11 euros for every euro
      invested. CONCLUSIONS: Within half a year, the cost of offering the preventive
      intervention was more than recouped. Offering the preventive intervention
      represents a favorable business case as seen from the employer's perspective.

PMID- 26224501
TI  - Seroprevalence and occupational risk survey for Coxiella burnetii among exposed
      workers in Sicily, Southern Italy.
AB  - OBJECTIVES: The aim of this survey was to assess the seroprevalence of antibodies
      against Coxiella burnetii (C. burnetii) in subjects at risk of exposure in
      Sicily, Southern Italy. MATERIAL AND METHODS: Prevalence of IgG antibodies to C.
      burnetii phase II antigens was evaluated by ELISA in a group of 140 workers at
      risk of exposure (38 veterinarians, 38 slaughterhouse workers, 44 livestock
      handlers, 20 laboratory and technical personnel) included in a medical
      surveillance program and in 42 control subjects. Positive samples were classified
      as suggestive of prior exposure to C. burnetii. RESULTS: Antibodies against C.
      burnetii were detected in 88 out of 140 (62.9%) exposed workers and in 6 out of
      42 (14.3%) subjects of the control group. The variables evaluated did not seem to
      have a significant effect on seropositivity to Coxiella with the exception of
      symptoms in the last 6 months preceding the survey. CONCLUSIONS: Our study
      demonstrated a high seroprevalence of C. burnetii in the group of exposed workers
      in comparison to non-exposed subjects of the control group. Clinical illness
      appears to be rare; nevertheless, physicians should consider Q fever in patients
      with compatible symptoms and occupational exposure to animals and their products.
      As aerosols represent the main route of infection in animals and humans, these
      workers are strongly advised to wear respiratory masks. In addition, occupational
      physicians should consider routine serologic evaluation and vaccination of
      occupationally exposed workers.

PMID- 26224502
TI  - Increased risk of horse sensitization in southwestern Iranian horse riders.
AB  - OBJECTIVES: The aim of this study has been to investigate the frequency of
      sensitization to horse allergens and clinical symptoms in horse riders. MATERIAL
      AND METHODS: A total of 42 horse riders and 50 healthy individuals were examined
      by means of skin prick tests for a panel of horse and common animal allergens,
      and pulmonary function tests were done by spirometry. RESULTS: The rate of
      sensitization to horse allergens was 31% as proven by the skin prick test in
      horse riders whereas horse sensitization was not seen in the control group.
      Occupational allergy symptoms were reported by 19 horse riders. Two horse riders
      with no history of clinical symptoms showed positive skin reactions to horse
      allergens. CONCLUSIONS: To decrease the high risk of occupational sensitization
      among horse riders, workplace conditions should be improved to reduce the load of
      airborne horse allergens.

PMID- 26224503
TI  - N-hexane neuropathy with vertigo and cold allodynia in a silk screen printer: A
      case study.
AB  - N-hexane neuropathy is an occupational disease caused by exposure to n-hexane,
      which is used as a solvent in silk screen printing. Here, we describe a 35-year
      old man, a silk screen printer by profession, who presented with dizziness,
      distal swelling of both lower limbs for 10 months and tingling and burning
      sensation in both feet for 9.5 months along with cold allodynia. The patient had
      normal results of a motor and sensory system examination, apart from an impaired
      temperature sense. Nerve conduction tests showed a conduction block in bilateral
      common peroneal nerves and absence of conduction in bilateral sural nerves. These
      symptoms resolved when further exposure to n-hexane was ceased but cold allodynia
      remained. Thus, cold allodynia and impaired temperature sense can be a
      manifestation of n-hexane neuropathy. Hence, abnormalities on nerve conduction
      studies can be detected in n-hexane neuropathy patients, even before clinical
      examination detects any such abnormalities. In the case of the patients
      presenting with sensory motor neuropathy, history of occupational exposure to n
      hexane becomes important, as the sooner the disease is detected, the better the
      chances of recovery. 

PMID- 26224505
TI  - President's report.

PMID- 26224504
TI  - History of previous bleeding and C-reactive protein improve assessment of
      bleeding risk in elderly patients (>= 80 years) with myocardial infarction.
AB  - We aimed to assess whether the CRUSADE risk score represents a robust instrument
      for stratification of bleeding risk in elderly myocardial infarction (MI)
      patients (>= 80 years) and further aimed to identify age-specific predictors of
      major bleeding events. Binary logistic regression models were applied to assess
      the effect of variables on the occurrence of bleeding events during hospital
      stay. Receiver operating characteristic (ROC) analysis was used to evaluate the
      discriminatory power. Out of 387 patients in the final study cohort, 74 patients
      (19.1 %) experienced a major bleeding event according to the definition of the
      International Society on Thrombosis and Haemostasis. The CRUSADE risk score
      demonstrated only a weak discriminatory power to predict bleeding in this group
      of patients (area under the ROC curve: 0.57 [0.51-0.65]; p=0.05). In the
      multivariate regression analysis, history of bleeding with an adjusted hazard
      ratio (HR) of 3.21 (95 % confidence interval: 1.29-8.03, p=0.01) and C-reactive
      protein with an adjusted HR per increase of 10 mg/l of 1.05 (1.01-1.10) were
      independent predictors of major bleeding. Integration of both variables into the
      CRUSADE score demonstrated a significantly improved performance for bleeding as
      indicated by a significant increase in the ROC analysis (area under the curve:
      0.64 vs 0.57; for comparison p< 0.045), net reclassification index (35.6 %;
      p=0.006) and integrated discrimination increment (0.0242; p=0.02). In conclusion,
      bleeding history and C-reactive protein significantly improve the modest
      predictive power of the CRUSADE risk score in elderly patients with MI. These
      results point towards a specific risk profile for bleeding events in this high
      risk group of patients. 

PMID- 26224506
TI  - The 18th APEC Conference, 9-10 April 2015, Amman-Jordan.

PMID- 26224509
TI  - Prognostic relevance of microsatellite instability in pT3N0M0 colon cancer: a
      population-based study.
AB  - Although surgery alone represents a curative approach for patients with pT3N0M0
      colon cancer, about 15-20% of these patients develop a relapse of disease.
      Microsatellite instability (MSI) is one of the most important molecular markers
      in colorectal cancer. The aim of this study was to investigate the prognostic
      relevance of MSI in all pT3N0M0 tumors recorded in the Cancer Registry of the
      Province of Modena--(Northern Italy) within the 2002-2006 period in patients who
      showed a relapse of disease during the 5-year period of follow-up (59 cases).
      They were compared to 59 controls similar in clinical and pathological features
      but with good prognosis. None of the subjects received adjuvant chemotherapy. MSI
      status was tested using BAT25, BAT26, NR24, and CAT25 fluorescent-labeled
      mononucleotide markers. The overall prevalence of MSI was 12.7% (15 of 118
      cases). MSI was detected mainly in mucinous adenocarcinoma (p < 0.003), in high
      grade tumors (p < 0.008), in right-sided neoplasms (p < 0.005), and in patients
      with a better prognosis, though the difference was not statistically significant
      (11/59 patients -18.6% vs 4/59 patients -6.7%; OR 0.36 CI 95% 0.11-1.15; p =
      0.08). However, in multivariate analysis, MSI status becomes the strongest
      independent factor associated with relapse (OR 0.21, CI 95% 0.06-0.81; p =
      0.023), together with mucinous histological type (OR 0.40, CI 90% 0.18-0.92). MSI
      is a relevant prognostic factor in stage pT3N0M0 colon cancer suitable to
      discriminate those patients with a high risk of relapse.

PMID- 26224510
TI  - August 2015 Update.

PMID- 26224511
TI  - Study of enrichment factors for six beta-blockers in aliphatic alcohols by hollow
      fiber liquid-phase microextraction.
AB  - The selectivity of a suitable organic solvent is key for extraction in liquid
      phase microextraction experiments. Nevertheless, the screening process remains a
      daunting task. Our research aimed to study the relationship between extraction
      efficiency and extraction solvents, analytes, and finally select the appropriate
      extraction solvent. In the present article, beta-blockers and six extraction
      solvents were chosen as the models and hollow-fiber liquid-phase microextraction
      was conducted. The relationship was built by statistical analysis on the data.
      Factors affecting extraction efficiency including the logarithms of the
      octanol/water partition coefficient (logPo/w ) of analytes, acid dissociation
      constants, the logarithms of the octanol/water partition coefficient of solvents
      and pH of the sample solution were investigated. The results showed that a low
      water solubility of extraction solvent is the foundation to ensure higher
      extraction efficiency. Moreover, when DeltalogPo/w > 0, a higher extraction
      efficiency is observed at lower DeltalogPo/w , on the contrary, when DeltalogPo/w
      < 0, extraction efficiency is higher as the absolute value of DeltalogPo/w
      becomes greater. Finally, the relationship between enrichment factor and
      extraction solvents, analytes was established and a helpful guidance was provided
      for the selection of an optimal solvent to obtain the best extraction efficiency
      by liquid-phase microextraction. 

PMID- 26224512
TI  - High protists diversity in the plankton of sulfurous lakes and lagoons examined
      by 18s rRNA gene sequence analyses.
AB  - Diversity of small protists was studied in sulfidic and anoxic (euxinic)
      stratified karstic lakes and coastal lagoons by 18S rRNA gene analyses. We
      hypothesized a major sulfide effect, reducing protist diversity and richness with
      only a few specialized populations adapted to deal with low-redox conditions and
      high-sulfide concentrations. However, genetic fingerprinting suggested similar
      ecological diversity in anoxic and sulfurous than in upper oxygen rich water
      compartments with specific populations inhabiting euxinic waters. Many of them
      agreed with genera previously identified by microscopic observations, but also
      new and unexpected groups were detected. Most of the sequences matched a rich
      assemblage of Ciliophora (i.e., Coleps, Prorodon, Plagiopyla, Strombidium,
      Metopus, Vorticella and Caenomorpha, among others) and algae (mainly
      Cryptomonadales). Unidentified Cercozoa, Fungi, Stramenopiles and Discoba were
      recurrently found. The lack of GenBank counterparts was higher in deep
      hypolimnetic waters and appeared differentially allocated in the different taxa,
      being higher within Discoba and lower in Cryptophyceae. A larger number of
      populations than expected were specifically detected in the deep sulfurous
      waters, with unknown ecological interactions and metabolic capabilities.

PMID- 26224513
TI  - Osteoblast differentiation is enhanced by a nano-to-micro hybrid titanium surface
      created by Yb:YAG laser irradiation.
AB  - OBJECTIVES: The aim of this study was to analyze the capacity of a new modified
      laser surface to stimulate calvarial osteoblasts isolated from neonatal mouse
      bones to differentiate and form mineralized nodules. METHODS: Titanium discs were
      subjectezd or not to laser irradiation according to specific parameters and
      characterized. Osteoblasts isolated from neonatal mouse calvaria were cultured
      over the discs, and the capacity of these cells to proliferate (MTT assay), form
      mineralized nodules (Alizarin red assay), and enhance alkaline phosphatase
      activity (ALPase activity) was analyzed. Real-time PCR was used for
      quantification of gene expression. RESULTS: Laser-irradiated titanium discs (L)
      presented a rough nano-to-micrometric oxidized surface contrasting with the
      smooth pattern on polished discs (P). The Ra on the micrometric level increased
      from 0.32 +/- 0.01 MUm on P surfaces to 10.57 +/- 0.39 MUm on L surfaces. When
      compared with P, L promoted changes in osteoblast morphology, increased
      mineralized nodule formation in osteoblasts cultured on the surfaces for 14 days,
      and enhanced ALPase activity at days 7 and 14. Transcription factors triggering
      osteoblast differentiation (Runx2 and Sp7) and genes encoding the bone
      extracellular matrix proteins collagen type-1 (Col1a1), osteopontin (Spp1), and
      osteocalcin (Bglap) were upregulated in cells on L surfaces compared with those
      on P surfaces at days 1-14. CONCLUSION: Laser treatment of titanium surfaces
      created a rough surface that stimulated osteoblast differentiation. CLINICAL
      RELEVANCE: Laser treatment of titanium generates a reproducible and efficient
      surface triggering osteoblast differentiation that can be of importance for
      osteointegration.

PMID- 26224514
TI  - Functional diversity and properties of multiple xylanases from Penicillium
      oxalicum GZ-2.
AB  - A multiple xylanase system with high levels of xylanase activity produced from
      Penicillium oxalicum GZ-2 using agricultural waste as a substrate has been
      previously reported. However, the eco-physiological properties and origin of the
      multiplicity of xylanases remain unclear. In the present study, eight active
      bands were detected using zymography, and all bands were identified as putative
      xylanases using MALDI-TOF-MS/MS. These putative xylanases are encoded by six
      different xylanase genes. To evaluate the functions and eco-physiological
      properties of xylanase genes, xyn10A, xyn11A, xyn10B and xyn11B were expressed in
      Pichia pastoris. The recombinant enzymes xyn10A and xyn10B belong to the
      glycoside hydrolase (GH) family 10 xylanases, while xyn11A and xyn11B belong to
      GH11 xylanases. Biochemical analysis of the recombinant proteins revealed that
      all enzymes exhibited xylanase activity against xylans but with different
      substrate specificities, properties and kinetic parameters. These results
      demonstrated that the production of multiple xylanases in P. oxalicum GZ-2 was
      attributed to the genetic redundancy of xylanases and the post-translational
      modifications, providing insight into a more diverse xylanase system for the
      efficient degradation of complex hemicelluloses. 

PMID- 26224515
TI  - Correction: Microfluidic pumping, routing and metering by contactless metal-based
      electro-osmosis.
AB  - Correction for 'Microfluidic pumping, routing and metering by contactless metal
      based electro-osmosis' by Xiaotong Fu et al., Lab Chip, 2015, DOI:
      10.1039/c5lc00504c. 

PMID- 26224518
TI  - Effect of daytime CO2 supplement on productivity and biochemical composition of
      Scenedesmus armatus under outdoor cultivation.
AB  - The cultivation of Scenedesmus armatus was carried out under outdoor Thailand
      climate conditions. The highest actual growth rate occurred at around 9:00 a.m.
      to 3:00 p.m., with a wide pH range of 6.4 to 11. The supply of CO2 had slight
      influence on growth characteristics but did exert some observable effects on
      nutritional accumulations. Adding CO2 from 2 to 15% by volume in the aeration
      (0.2 vvm) caused an increase in lipid and protein from 19.8 to 25.6 and 37.8 to
      48.2% w/w, respectively, whereas carbohydrate decreased from 42.5 to 26.2% w/w.
      Scenedesmus armatus cultivated with 2% CO2-enriched air provided the highest the
      average of the average biomass productivity of 91.25 mg L(-1) d(-1), which
      corresponded to a CO2 fixation of 165 mg CO2 L(-1) d(-1) with the average lipid,
      protein, and carbohydrate productivities of 22.24, 38.34, and 30.67 mg L(-1) d(
      1).

PMID- 26224517
TI  - Role of Oxidative Stress in the Worsening of Neurologic Wilson Disease Following
      Chelating Therapy.
AB  - Patients with neurologic Wilson disease (NWD) may worsen on treatment, but there
      is no study evaluating the role of oxidative stress. We report the role of plasma
      glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA) in
      the worsening of NWD following treatment. Fifty-one treatment-naive NWD patients
      were subjected to detailed clinical evaluation. The severity of NWD was noted,
      and dystonia was measured by Burke-Fahn-Marsden (BFM) score. Their hematological,
      serum chemistry, ultrasound abdomen and cranial MRI changes were noted. Plasma
      GSH, TAC and MDA, serum free copper (Cu) and 24-h urinary Cu were measured at
      admission and at 3 and 6 months after treatment. The patients were considered
      worsened if there was one or more grade deterioration in severity scale, >10 %
      deterioration in BFM score or appearance of new neurologic signs. The median age
      of the patients was 11 (5-37) years, and 12 were females. Following treatment, 25
      patients improved, 12 worsened, and 14 had stationary course. The worsened group
      at 3 months had lower GSH (1.99 +/- 0.17 vs. 2.30 +/- 0.30 mg/dl; P = 0.004) and
      TAC (1.59 +/- 0.12 vs. 1.82 +/- 0.17 mmol Trolox equivalent/L; P = 0.001) and
      higher MDA (5.24 +/- 0.22 vs. 4.34 +/- 0.46 nmol/ml; P < 0.001) levels compared
      to the improved group. These changes were associated with increased serum free Cu
      (41.81 +/- 3.31 vs. 35.62 +/- 6.40 ug/dl; P = 0.02) and 24-h urinary Cu (206.42
      +/- 41.61 vs. 121.99 +/- 23.72 ug/24 h; P < 0.001) in the worsened compared to
      the improved group. All the patients having worsening were on penicillamine.
      Worsening following chelating treatment in NWD may be due to oxidative stress
      which is induced by increased serum free Cu. These results may have future
      therapeutic implication and needs further study.

PMID- 26224520
TI  - Atomic force microscope, molecular imaging, and analysis.
AB  - Image visibility is a central issue in analyzing all kinds of microscopic images.
      An increase of intensity contrast helps to raise the image visibility, thereby to
      reveal fine image features. Accordingly, a proper evaluation of results with
      current imaging parameters can be used for feedback on future imaging
      experiments. In this work, we have applied the Laplacian function of image
      intensity as either an additive component (Laplacian mask) or a multiplying
      factor (Laplacian weight) for enhancing image contrast of high-resolution AFM
      images of two molecular systems, an unknown protein imaged in air, provided by
      AFM COST Action TD1002 (http://www.afm4nanomedbio.eu/), and tobacco mosaic virus
      (TMV) particles imaged in liquid. Based on both visual inspection and
      quantitative representation of contrast measurements, we found that the Laplacian
      weight is more effective than the Laplacian mask for the unknown protein, whereas
      for the TMV system the strengthened Laplacian mask is superior to the Laplacian
      weight. The present results indicate that a mathematical function, as exemplified
      by the Laplacian function, may yield varied processing effects with different
      operations. To interpret the diversity of molecular structure and topology in
      images, an explicit expression for processing procedures should be included in
      scientific reports alongside instrumental setups.

PMID- 26224516
TI  - The Dynamics of Interactions Among Immune and Glioblastoma Cells.
AB  - Glioblastoma is the most common intracranial malignancy that constitutes about 50
      % of all gliomas. Despite aggressive, multimodal therapy consisting of surgery,
      radiation, and chemotherapy, the outcome of patients with glioblastoma remains
      poor with 5-year survival rates of <10 %. Resistance to conventional therapies is
      most likely caused by several factors. Alterations in the functions of local
      immune mediators may represent a critical contributor to this resistance. The
      tumor microenvironment contains innate and adaptive immune cells in addition to
      the cancer cells and their surrounding stroma. These various cells communicate
      with each other by means of direct cell-cell contact or by soluble factors
      including cytokines and chemokines, and act in autocrine and paracrine manners to
      modulate tumor growth. There are dynamic interactions among the local immune
      elements and the tumor cells, where primarily the protective immune cells attempt
      to overcome the malignant cells. However, by developing somatic mutations and
      epigenetic modifications, the glioblastoma tumor cells acquire the capability of
      counteracting the local immune responses, and even exploit the immune cells and
      products for their own growth benefits. In this review, we survey those immune
      mechanisms that likely contribute to glioblastoma pathogenesis and may serve as a
      basis for novel treatment strategies.

PMID- 26224521
TI  - Local sample thickness determination via scanning transmission electron
      microscopy defocus series.
AB  - The usable aperture sizes in (scanning) transmission electron microscopy ((S)TEM)
      have significantly increased in the past decade due to the introduction of
      aberration correction. In parallel with the consequent increase of convergence
      angle the depth of focus has decreased severely and optical sectioning in the
      STEM became feasible. Here we apply STEM defocus series to derive the local
      sample thickness of a TEM sample. To this end experimental as well as simulated
      defocus series of thin Si foils were acquired. The systematic blurring of high
      resolution high angle annular dark field images is quantified by evaluating the
      standard deviation of the image intensity for each image of a defocus series. The
      derived dependencies exhibit a pronounced maximum at the optimum defocus and drop
      to a background value for higher or lower values. The full width half maximum
      (FWHM) of the curve is equal to the sample thickness above a minimum thickness
      given by the size of the used aperture and the chromatic aberration of the
      microscope. The thicknesses obtained from experimental defocus series applying
      the proposed method are in good agreement with the values derived from other
      established methods. The key advantages of this method compared to others are its
      high spatial resolution and that it does not involve any time consuming
      simulations. 

PMID- 26224523
TI  - A Phase-Based Electrical Plethysmography Approach to Bladder Volume Measurement.
AB  - Neuromodulation approaches to treating lower urinary tract dysfunction could be
      substantially improved by a sensor able to detect when the bladder is full. A
      number of approaches to this problem have been proposed, but none has been found
      entirely satisfactory. Electrical plethysmography approaches attempt to relate
      the electrical impedance of the bladder to its volume, but have previously
      focused only on the amplitudes of the measured signals. We investigated whether
      the phase relationships between sinusoidal currents applied through a pair of
      stimulating electrodes and measured through a pair of recording electrodes could
      provide information about bladder volume. Acute experiments in a rabbit model
      were used to investigate how phase-to-volume or amplitude-to-volume regression
      models could be used to predict bladder volumes in future recordings, with and
      without changes to the saline conductivity. Volume prediction errors were found
      to be 6.63 +/- 1.12 mL using the phase information and 8.32 +/- 3.88 mL using the
      amplitude information (p = 0.44 when comparing the phase and amplitude results, n
      = 6), where the volume of the filled bladder was about 25 mL. When a full/empty
      binary decision rule was applied based on the regression model, the difference
      between the actual threshold that would result from this rule and the desired
      threshold was found to be 4.24 +/- 0.65 mL using the phase information and 106.92
      +/- 189.82 mL using the amplitude information (p = 0.03, n = 6). Our results
      suggest that phase information can form the basis for more effective and robust
      electrical plethysmography approaches to bladder volume measurement.

PMID- 26224522
TI  - Emerging Trends in Heart Valve Engineering: Part IV. Computational Modeling and
      Experimental Studies.
AB  - In this final portion of an extensive review of heart valve engineering, we focus
      on the computational methods and experimental studies related to heart valves.
      The discussion begins with a thorough review of computational modeling and the
      governing equations of fluid and structural interaction. We then move onto
      multiscale and disease specific modeling. Finally, advanced methods related to in
      vitro testing of the heart valves are reviewed. This section of the review series
      is intended to illustrate application of computational methods and experimental
      studies and their interrelation for studying heart valves. 

PMID- 26224525
TI  - Terrain and Direction Classification of Locomotion Transitions Using
      Neuromuscular and Mechanical Input.
AB  - To perform seamless transitions in powered lower limb prostheses, accurate
      classification of transition type is required a priori. We propose a structure to
      detect direction (ascent or descent) and terrain (ramp or stairs) patterns when a
      person transitions from over ground to stairs or ramp locomotion. We compared
      electromyography (EMG) and accelerometry performance with an emphasis on sensor
      fusion for improving classification. Seven healthy subjects were recruited for
      this initial study. Data were collected with accelerometers and EMG electrodes on
      the dominant leg, while subjects transitioned from over ground to ramp (ascent
      and descent) and stair (ascent and descent) locomotion. Linear discriminant
      analysis and support vector machine approaches were used as classifiers using
      feature spaces of both sensor types. The results indicate that transitions are
      better classified as terrain type than direction type (p < 0.001), suggesting a
      terrain focused approach for an efficient structure. We also show that EMG and
      accelerometry data sources are complementary across the transitional gait cycle,
      suggesting sensor fusion for robust classification. These findings suggest that a
      terrain and direction focused classification approach will be useful for
      inclusion in classification approaches utilized in lower limb amputee samples.

PMID- 26224524
TI  - Regurgitation Hemodynamics Alone Cause Mitral Valve Remodeling Characteristic of
      Clinical Disease States In Vitro.
AB  - Mitral valve regurgitation is a challenging clinical condition that is frequent,
      highly varied, and poorly understood. While the causes of mitral regurgitation
      are multifactorial, how the hemodynamics of regurgitation impact valve tissue
      remodeling is an understudied phenomenon. We employed a pseudo-physiological flow
      loop capable of long-term organ culture to investigate the early progression of
      remodeling in living mitral valves placed in conditions resembling mitral valve
      prolapse (MVP) and functional mitral regurgitation (FMR). Valve geometry was
      altered to mimic the hemodynamics of controls (no changes from native geometry),
      MVP (5 mm displacement of papillary muscles towards the annulus), and FMR (5 mm
      apical, 5 mm lateral papillary muscle displacement, 65% larger annular area).
      Flow measurements ensured moderate regurgitant fraction for regurgitation groups.
      After 1-week culture, valve tissues underwent mechanical and compositional
      analysis. MVP conditioned tissues were less stiff, weaker, and had elevated
      collagen III and glycosaminoglycans. FMR conditioned tissues were stiffer, more
      brittle, less extensible, and had more collagen synthesis, remodeling, and
      crosslinking related enzymes and proteoglycans, including decorin, matrix
      metalloproteinase-1, and lysyl oxidase. These models replicate clinical findings
      of MVP (myxomatous remodeling) and FMR (fibrotic remodeling), indicating that
      valve cells remodel extracellular matrix in response to altered mechanical
      homeostasis resulting from disease hemodynamics.

PMID- 26224526
TI  - Corn stover harvest increases herbicide movement to subsurface drains - Root Zone
      Water Quality Model simulations.
AB  - BACKGROUND: Crop residue removal for bioenergy production can alter soil
      hydrologic properties and the movement of agrochemicals to subsurface drains. The
      Root Zone Water Quality Model (RZWQM), previously calibrated using measured flow
      and atrazine concentrations in drainage from a 0.4 ha chisel-tilled plot, was
      used to investigate effects of 50 and 100% corn (Zea mays L.) stover harvest and
      the accompanying reductions in soil crust hydraulic conductivity and total
      macroporosity on transport of atrazine, metolachlor and metolachlor oxanilic acid
      (OXA). RESULTS: The model accurately simulated field-measured metolachlor
      transport in drainage. A 3 year simulation indicated that 50% residue removal
      reduced subsurface drainage by 31% and increased atrazine and metolachlor
      transport in drainage 4-5-fold when surface crust conductivity and macroporosity
      were reduced by 25%. Based on its measured sorption coefficient, approximately
      twofold reductions in OXA losses were simulated with residue removal. CONCLUSION:
      The RZWQM indicated that, if corn stover harvest reduces crust conductivity and
      soil macroporosity, losses of atrazine and metolachlor in subsurface drainage
      will increase owing to reduced sorption related to more water moving through
      fewer macropores. Losses of the metolachlor degradation product OXA will decrease
      as a result of the more rapid movement of the parent compound into the soil.
      Published 2015. This article is a U.S. Government work and is in the public
      domain in the USA.

PMID- 26224527
TI  - Pelvic floor changes: consequences of pregnancy and delivery.

PMID- 26224529
TI  - Pleiotropy and the evolution of floral integration.
AB  - Floral traits often show correlated variation, both within and across species.
      One explanation for this pattern of floral integration is that different elements
      of floral phenotypes are controlled by the same genes, that is, that the genetic
      architecture is pleiotropic. Recent studies from a range of model systems suggest
      that the pleiotropy is common among the loci responsible for floral divergence.
      Moreover, the effects of allelic substitutions at these loci are overwhelmingly
      aligned with direction of divergence, suggesting that the nature of the
      pleiotropic effects was adaptive. Molecular genetic studies have revealed the
      functional basis for some of these effects, although much remains to be
      discovered with respect to the molecular, biochemical and developmental
      mechanisms underlying most quantitative trait loci (QTL) responsible for floral
      differences. Developing a detailed understanding of the nature of pleiotropic
      mutations and their phenotypic consequences is crucial for modeling how the
      genetic architecture of trait variation influences the tempo and trajectory of
      floral evolution.

PMID- 26224528
TI  - Prediction of therapy response in acromegalic patients under pegvisomant therapy
      within the German ACROSTUDY cohort.
AB  - PURPOSE: This study aimed at investigating predicting factors for therapy
      response under growth hormone receptor antagonist therapy with a focus on
      subjective and patient-oriented measures. METHODS: Observational, multicenter
      nested-cohort study including 271 selected patients with the diagnosis of
      acromegaly and a minimum of one-year follow-up period within the German ACROSTUDY
      cohort (total cohort: n = 514). Outcome measures were the change of the biomarker
      IGF-1 (IGF-1 change and IGF-1 normalisation) between baseline and after 1 year of
      pegvisomant therapy (12 +/- 6 months). Main predictors were patient-assessed
      subjective measures according to the Patient-Assessed Acromegaly Symptom
      Questionnaire (PASQ) in conjugation with age, gender, BMI, max. dosage of
      pegvisomant at follow-up and IGF-1 before the start of pegvisomant therapy.
      RESULTS: The mean age of the study population was 51.2 (13.9) years and the mean
      BMI was 29.5 (5.1) kg/m(2). In adjusted analyses, none of the individual
      perceived health (PASQ) scores, but age, BMI and IGF-1 at baseline were
      predictive for an IGF-1 decrease after 1 year of pegvisomant therapy and BMI and
      IGF-1, but equally none of the PASQ items, were predicting IGF-1 normalisation.
      CONCLUSIONS: Age, BMI and baseline IGF-1 but not subjective perceived health
      measures predict therapy response under second line medical therapy with
      pegvisomant.

PMID- 26224530
TI  - Assessing the optimal strategy for dual antiplatelet therapy.
AB  - Coronary artery disease remains a leading cause of morbidity and mortality
      worldwide. Each year, millions of patients undergo stent placement to treat
      coronary artery disease. As stents are prone to thrombosis, which can potentially
      be devastating, patients are treated with dual antiplatelet therapy with aspirin
      plus a thienopyridine for at least 6-12 months after stent placement. New
      evidence suggests that long-term dual antiplatelet therapy beyond 1 year prevents
      ischemic events but also leads to increased risk of bleeding. To determine the
      optimal strategy for dual antiplatelet therapy after stent placement, the
      benefits and risks must be carefully considered and individualized for each
      patient. 

PMID- 26224533
TI  - OVERLOAD of joints and its role in osteoarthritis : Towards understanding and
      preventing progression of primary osteoarthritis. English version.

PMID- 26224532
TI  - [Empowerment by patient education in rheumatology].
AB  - Due to the chronic course, rheumatic diseases may be associated with both long
      lasting pain and movement limitations. Those afflicted by these disorders thus
      face continuous challenges regarding both adapting to their illness as well as
      changing their lifestyle habits, for example increasing the physical activity
      levels. However, patient education may provide patients with the competencies
      they need to cope with their illness and modify their behavior. Therefore,
      patient education programs are core elements of rehabilitation in rheumatology.
      The German Society for Rheumatology has performed pioneering work concerning
      conceptualization and evaluation of standardized educational programs. In this
      article some more recent developments and up to date standards for contents and
      didactics of self-management programs are presented. Empowerment may be
      considered the overriding aim of these programs, i.e. enabling patients to make
      informed decisions in situations where their health is involved. Patient-centered
      didactic methods as used in state of the art concepts mirror the empowerment
      approach. To foster sustainability of lifestyle changes, detailed planning of
      behavioral modifications is recommended, thus increasing the chance of
      transferring changes adopted during rehabilitation into everyday living. Such
      methods have been proven to be effective and are employed in the updated
      education concept for patients with fibromyalgia syndrome, which is described
      here as an example. The Centre for Patient Education offers support in updating
      and evaluating patient education concepts. 

PMID- 26224534
TI  - The complex phylogeography of the Indo-Malayan Alophoixus bulbuls with the
      description of a putative new ring species complex.
AB  - The Indo-Malayan bioregion has provided some of the most spectacular discoveries
      of new vertebrate species (e.g. saola, khanyou, bare-faced bulbul) over the last
      25 years. Yet, very little is known about the processes that led to the current
      biodiversity in this region. We reconstructed the phylogeographic history of a
      group of closely related passerines, the Alophoixus bulbuls. These birds are
      continuously distributed in Indo-Malaya around the Thailand lowlands such that
      their distribution resembles a ring. Our analyses revealed a single colonization
      event of the mainland from Sundaland with sequential divergence of taxa from
      southwest to northeast characterized by significant gene flow between parapatric
      taxa, and reduced or ancient gene flow involving the two taxa at the extremities
      of the ring. We detected evidence of population expansion in two subspecies,
      including one that was involved in the closing of the ring. Hence, our analyses
      indicate that the diversification pattern of Alophoixus bulbuls fits a ring
      species model driven by geographic isolation. To our knowledge, the Alophoixus
      bulbuls represent the first case of a putative broken ring species complex in
      Indo-Malaya. We also discuss the implications of our results on our understanding
      of the biogeography in Indo-Malaya. 

PMID- 26224535
TI  - Recessive ITPA mutations cause an early infantile encephalopathy.
AB  - OBJECTIVE: To identify the etiology of a novel, heritable encephalopathy in a
      small group of patients. METHODS: Magnetic resonance imaging (MRI) pattern
      analysis was used to select patients with the same pattern. Homozygosity mapping
      and whole exome sequencing (WES) were performed to find the causal gene
      mutations. RESULTS: Seven patients from 4 families (2 consanguineous) were
      identified with a similar MRI pattern characterized by T2 signal abnormalities
      and diffusion restriction in the posterior limb of the internal capsule, often
      also optic radiation, brainstem tracts, and cerebellar white matter, in
      combination with delayed myelination and progressive brain atrophy. Patients
      presented with early infantile onset encephalopathy characterized by progressive
      microcephaly, seizures, variable cardiac defects, and early death. Metabolic
      testing was unrevealing. Single nucleotide polymorphism array revealed 1
      overlapping homozygous region on chromosome 20 in the consanguineous families. In
      all patients, WES subsequently revealed recessive predicted loss of function
      mutations in ITPA, encoding inosine triphosphate pyrophosphatase (ITPase). ITPase
      activity in patients' erythrocytes and fibroblasts was severely reduced.
      INTERPRETATION: Until now ITPA variants have only been associated with adverse
      reactions to specific drugs. This is the first report associating ITPA mutations
      with a human disorder. ITPase is important in purine metabolism because it
      removes noncanonical nucleotides from the cellular nucleotide pool. Toxicity of
      accumulated noncanonical nucleotides, leading to neuronal apoptosis and
      interference with proteins normally using adenosine triphosphate/guanosine
      triphosphate, probably explains the disease. This study confirms that combining
      MRI pattern recognition to define small, homogeneous patient groups with WES is a
      powerful approach for providing a fast diagnosis in patients with an unclassified
      genetic encephalopathy.

PMID- 26224536
TI  - Assessment of metastatic colorectal cancer with hybrid imaging: comparison of
      reading performance using different combinations of anatomical and functional
      imaging techniques in PET/MRI and PET/CT in a short case series.
AB  - PURPOSE: The purpose was to investigate the diagnostic performance of different
      combinations of anatomical and functional imaging techniques in PET/MRI and
      PET/CT for the evaluation of metastatic colorectal cancer lesions. METHODS: Image
      data of 15 colorectal cancer patients (FDG-PET/CT and subsequent FDG-PET/MRI)
      were retrospectively evaluated by two readers in five reading sessions: MRI
      (morphology) alone, MRI/diffusion-weighted MRI (DWI), MRI/PET, MRI/DWI/PET; and
      PET/CT. Diagnostic performance of lesion detection with each combination was
      assessed in general and organ-based. The reference standard was given by
      histology and/or follow-up imaging. Separate analysis of mucinous tumours was
      performed. RESULTS: One hundred and eighty lesions (110 malignant) were evaluated
      (intestine n = 6, liver n = 37, lymph nodes n = 55, lung n = 4, and peritoneal n
      = 74). The overall lesion-based diagnostic accuracy was 0.46 for MRI, 0.47 for
      MRI/DWI, 0.57 for MRI/PET, 0.69 for MRI/DWI/PET and 0.66 for PET/CT. In the organ
      based assessment, MRI/DWI/PET showed the highest accuracy for liver metastases
      (0.74), a comparable accuracy to PET/CT in peritoneal lesions (0.55), and in
      lymph node metastases (0.84). The accuracy in mucinous tumour lesions was limited
      in all modalities (MRI/DWI/PET = 0.52). CONCLUSIONS: PET/MRI including DWI is
      comparable to PET/CT in the evaluation of colorectal cancer metastases, with a
      markedly higher accuracy when using combined imaging data than the modalities
      separately. Further improvement is needed in the imaging of peritoneal
      carcinomatosis and mucinous tumours.

PMID- 26224537
TI  - The protein and transcript profiles of human semen.
AB  - The increasing use of "-omics" (genomic, transcriptomic, proteomic, epigenomic,
      and metabolomic) high-throughput measurement technologies over the past decade is
      beginning to reveal the complexity of human biology and physiology through the
      interactions of DNA, RNA, related proteins and small molecules. In reproductive
      medicine, the majority of this work, has thus far focused on the female factors,
      e.g., the oocyte, since they provide both the environment and the majority of
      elements required for embryogenesis. State-of-the-art sequencing and
      computational analyses have enabled a deeper understanding of the underlying
      components. Contrary to being simply a silent delivery vehicle to the oocyte of
      the packaged male DNA, sperm provide both a specific epigenetically marked genome
      together with a complex population of RNAs and proteins that are crucial for
      early embryogenesis. In addition to the sperm, seminal fluid appears to serve
      multiple roles providing a supplementary series of components that allow the
      sperm to successfully reach and fertilize the oocyte and prepare the female
      immune system to tolerate the semiallosteric embryo. A global analysis and review
      of what is presently known regarding the unique role of each component of the
      male factor and their associated interactions begins to shed light on this
      emergent field.

PMID- 26224538
TI  - The challenges involved in elucidating the molecular basis of sperm-egg
      recognition in mammals and approaches to overcome them.
AB  - Sexual reproduction is used by many different organisms to create a new
      generation of genetically distinct progeny. Cells originating from separate sexes
      or mating types segregate their genetic material into haploid gametes which must
      then recognize and fuse with each other in a process known as fertilization to
      form a diploid zygote. Despite the central importance of fertilization, we know
      remarkably little about the molecular mechanisms that are involved in how gametes
      recognize each other, particularly in mammals, although the proteins that are
      displayed on their surfaces are almost certainly involved. This paucity of
      knowledge is largely due to both the unique biological properties of mammalian
      gametes (sperm and egg) which make them experimentally difficult to manipulate,
      and the technical challenges of identifying interactions between membrane
      embedded cell surface receptor proteins. In this review, we will discuss our
      current knowledge of animal gamete recognition, highlighting where important
      contributions to our understanding were made, why particular model systems were
      helpful, and why progress in mammals has been particularly challenging. We
      discuss how the development of mammalian in vitro fertilization and targeted gene
      disruption in mice were important technological advances that triggered progress.
      We argue that approaches employed to discover novel interactions between cell
      surface gamete recognition proteins should account for the unusual biochemical
      properties of membrane proteins and the typically highly transient nature of
      their interactions. Finally, we describe how these principles were applied to
      identify Juno as the egg receptor for sperm Izumo1, an interaction that is
      essential for mammalian fertilization.

PMID- 26224539
TI  - Inhibition of differentiation and function of osteoclasts by dimethyl sulfoxide
      (DMSO).
AB  - Dimethyl sulfoxide (DMSO) is an FDA-approved organosulfur solvent that is
      reported to have therapeutic value in osteoarthritis and osteopenia. DMSO is used
      as a cryoprotectant for the cryopreservation of bone grafts and mesenchymal stem
      cells which are later used for bone repair. It is also used as a solvent in the
      preparation of various scaffolds used for bone tissue engineering purposes. DMSO
      has been reported to inhibit osteoclast formation in vitro but the mechanism
      involved has remained elusive. We investigated the effect of DMSO on osteoclast
      differentiation and function using a conventional model system of RAW 264.7
      cells. The differentiation of RAW 264.7 cells was induced by adding 50 ng/ml
      RANKL and the effect of DMSO (0.01 and 1% v/v) on RANKL-induced
      osteoclastogenesis was investigated. Addition of 1% DMSO significantly inhibited
      RANKL-induced formation of TRAP+, multinucleated, mature osteoclasts and
      osteoclast late-stage precursors (c-Kit(-) c-Fms(+) Mac-1(+) RANK(+)). While DMSO
      did not inhibit proliferation per se, it did inhibit the effect of RANKL on
      proliferation of RAW 264.7 cells. Key genes related to osteoclast function (TRAP,
      Integrin alphaVbeta3, Cathepsin K and MMP9) were significantly down-regulated by
      DMSO. RANKL-induced expression of RANK gene was significantly reduced in the
      presence of DMSO. Our data, and reports from other investigators, that DMSO
      enhances osteoblastic differentiation of mesenchymal stem cells and also prevents
      bone loss in ovarietcomized rats, suggest that DMSO has tremendous potential in
      the treatment of osteoporosis and bone diseases arising from uncontrolled
      activities of the osteoclasts.

PMID- 26224540
TI  - Combined effect of ligament stem cells and umbilical-cord-blood-derived CD34+
      cells on ligament healing.
AB  - Transplantation of ligament-tissue-derived stem cells has become a promising
      approach in the repair of injured ligament. Neovascularization plays an important
      role in ligament healing and remodeling. Recently, human umbilical-cord-blood
      derived CD34+ cells have been reported to contribute to neoangiogenesis.
      Therefore, we performed a series of experiments to test our hypothesis that the
      combination of medial collateral ligament stem cells (MCL-SCs) and umbilical-cord
      blood-derived CD34+ cells has synergistic effects on tendon healing. MCL-SCs and
      umbilical-cord-blood-derived CD34+ cells were isolated and cultured. Rat MCL
      injury was treated by MCL-SCs and/or CD34+ cells. Response to the cell therapy
      was assessed by gross observation, histological evaluation and biomechanical
      testing at 2 and 4 weeks after each treatment. Although each cell therapy group
      induced macroscopic and morphological recovery in healing MCLs, the combined use
      of MCL-SCs/CD34+ cells led to further improvement in healing quality. Capillary
      density was significantly higher in the CD34+ cell transplantation groups than in
      the other groups at week 2. Biomechanical testing demonstrated that the failure
      load of the healing ligament was greatest in the combination therapy group. The
      combination of MCL-SCs and CD34+ cells as a cell therapeutic thus enhances
      healing and restores biomechanical function toward normal after MCL injury. The
      findings obtained in our study suggest that the combination of MCL-SCs and CD34+
      cells transplantation represents a promising strategy for ligament injury.

PMID- 26224541
TI  - Erratum to: growth/differentiation factor-15 and its role in peripheral nervous
      system lesion and regeneration.

PMID- 26224543
TI  - Long-Term Effects of Low-Dose Spironolactone on Chronic Dialysis Patients: A
      Randomized Placebo-Controlled Study.
AB  - The purpose of this 2-year multicentric, randomized, placebo-controlled study was
      to evaluate the long-term effects and adverse effects of spironolactone on
      chronic dialysis patients. A total of 253 non-heart failure dialysis patients
      with end-stage renal disease were randomly assigned to 2-year treatment with
      spironolactone (25 mg once daily, n=125) or a matching placebo (n=128) as add-on
      therapy. The primary outcome was a composite of death from cardiocerebrovascular
      (CCV) events, aborted cardiac arrest, and sudden cardiac death, and the secondary
      outcome was death from all causes. Other CCV-related indexes such as left
      ventricular mass index, left ventricular ejection fraction, heart rate
      variability, vascular endothelial function, and blood pressure-lowering effect
      were analyzed for patients who completed the whole 2-year follow-up study.
      Sociodemographic, clinical, and relevant laboratory data were also collected.
      During the 2-year follow-up, the primary outcome occurred less frequently in the
      spironolactone group vs the control group (7.2% vs 18.0%; adjusted hazard ratio
      [HR], 0.42; 95% confidence interval [CI], 0.26-0.78). Death from CCV events
      occurred in 4.0% of patients in the spironolactone group and in 11.7% of patients
      in the control group. Neither aborted cardiac arrest nor sudden cardiac death was
      significantly reduced by spironolactone treatment. The secondary outcome occurred
      less frequently in the spironolactone group vs the control group (9.6% vs 19.5%;
      adjusted HR, 0.52; 95% CI, 0.29-0.94). Other CCV-related indexes except for heart
      rate variability were significantly improved. This study demonstrates that use of
      low-dose spironolactone in non-heart failure dialysis patients can effectively
      reduce the risks of both CCV morbidity and mortality with few side effects.
      Moreover, the beneficial effect was mediated through improving the endothelial
      function or reducing left ventricular size independent of blood pressure changes,
      rather than mediation through changes in salt or potassium handling in the
      kidney.

PMID- 26224542
TI  - Activation of TRESK channels by the inflammatory mediator lysophosphatidic acid
      balances nociceptive signalling.
AB  - In dorsal root ganglia (DRG) neurons TRESK channels constitute a major current
      component of the standing outward current IKSO. A prominent physiological role of
      TRESK has been attributed to pain sensation. During inflammation mediators of
      pain e.g. lysophosphatidic acid (LPA) are released and modulate nociception. We
      demonstrate co-expression of TRESK and LPA receptors in DRG neurons. Heterologous
      expression of TRESK and LPA receptors in Xenopus oocytes revealed augmentation of
      basal K(+) currents upon LPA application. In DRG neurons nociception can result
      from TRPV1 activation by capsaicin or LPA. Upon co-expression in Xenopus oocytes
      LPA simultaneously increased both depolarising TRPV1 and hyperpolarising TRESK
      currents. Patch-clamp recordings in cultured DRG neurons from TRESK[wt] mice
      displayed increased IKSO after application of LPA whereas under these conditions
      IKSO in neurons from TRESK[ko] mice remained unaltered. Under current-clamp
      conditions LPA application differentially modulated excitability in these
      genotypes upon depolarising pulses. Spike frequency was attenuated in TRESK[wt]
      neurons and, in contrast, augmented in TRESK[ko] neurons. Accordingly, excitation
      of nociceptive neurons by LPA is balanced by co-activation of TRESK channels.
      Hence excitation of sensory neurons is strongly controlled by the activity of
      TRESK channels, which therefore are good candidates for the treatment of pain
      disorders. 

PMID- 26224544
TI  - Arterial Vascularization of the Gastrointestinal Tract of the Pampas Deer
      (Ozotoceros bezoarticus, Linnaeus, 1758).
AB  - Based on gross dissection of fifteen adult animals (11 females, 4 males), we
      described the arterial supply of the stomach and intestines of the pampas deer
      (Ozotoceros bezoarticus), a South American endangered species. The coeliac artery
      emitted the splenic, left gastric and hepatic arteries. The splenic artery
      directed towards the spleen, and the right ruminal artery, which is its only
      collateral directed towards the stomach, being the main artery of the rumen. The
      left gastric artery gave origin to the left ruminal, the reticular and the left
      gastroepiploic arteries. The left gastroepiploic artery originated the reticular
      accessory artery. Both arteries, gastric and left gastroepiploic, anastomosed
      their right counterparts derived from the hepatic artery on the curvatures of the
      abomasum. The cranial mesenteric artery irrigated the second half of the duodenum
      until the beginning of the descending colon. The thickest branch emitted by the
      cranial mesenteric artery was the ileocolic artery, which was destined to the
      ascending colon, caecum and ileum. The colic branches and the right colic
      arteries were irradiated on the right surface of the spiral loop of the ascending
      colon and distributed to both centripetal and centrifugal coils of the ascending
      colon; the colic branches were also anastomosed with the last jejunals and ileals
      and with the right colic arteries. There were no variations in the origin of any
      of the main branches derived from the coeliac and cranial mesenteric arteries.
      This species had a basic pattern of arterial distribution similar to small
      domestic ruminants. 

PMID- 26224545
TI  - gamma-Tubulin complex in Trypanosoma brucei: molecular composition, subunit
      interdependence and requirement for axonemal central pair protein assembly.
AB  - gamma-Tubulin complex constitutes a key component of the microtubule-organizing
      center and nucleates microtubule assembly. This complex differs in complexity in
      different organisms: the budding yeast contains the gamma-tubulin small complex
      (gammaTuSC) composed of gamma-tubulin, gamma-tubulin complex protein (GCP)2 and
      GCP3, whereas animals contain the gamma-tubulin ring complex (gammaTuRC) composed
      of gammaTuSC and three additional proteins, GCP4, GCP5 and GCP6. In Trypanosoma
      brucei, the composition of the gamma-tubulin complex remains elusive, and it is
      not known whether it also regulates assembly of the subpellicular microtubules
      and the spindle microtubules. Here we report that the gamma-tubulin complex in T.
      brucei is composed of gamma-tubulin and three GCP proteins, GCP2-GCP4, and is
      primarily localized in the basal body throughout the cell cycle. Depletion of
      GCP2 and GCP3, but not GCP4, disrupted the axonemal central pair microtubules,
      but not the subpellicular microtubules and the spindle microtubules. Furthermore,
      we showed that the gammaTuSC is required for assembly of two central pair
      proteins and that gammaTuSC subunits are mutually required for stability.
      Together, these results identified an unusual gamma-tubulin complex in T. brucei,
      uncovered an essential role of gammaTuSC in central pair protein assembly, and
      demonstrated the interdependence of individual gammaTuSC components for
      maintaining a stable complex. 

PMID- 26224546
TI  - Excitatory and inhibitory innervation of the mouse orofacial motor nuclei: A
      stereological study.
AB  - Neurons in the trigeminal (Mo5), facial (Mo7), ambiguus (Amb), and hypoglossal
      (Mo12) motor nuclei innervate jaw, facial, pharynx/larynx/esophagus, and tongue
      muscles, respectively. They are essential for movements subserving feeding,
      exploration of the environment, and social communication. These neurons are
      largely controlled by sensory afferents and premotor neurons of the reticular
      formation, where central pattern generator circuits controlling orofacial
      movements are located. To provide a description of the orofacial nuclei of the
      adult mouse and to ascertain the influence of excitatory and inhibitory afferents
      upon them, we used stereology to estimate the number of motoneurons as well as of
      varicosities immunopositive for glutamate (VGluT1+, VGluT2+) and GABA/glycine
      (known as VIAAT+ or VGAT+) vesicular transporters in the Mo5, Mo7, Amb, and Mo12.
      Mo5, Mo7, Amb, and Mo12 contain ~1,000, ~3,000, ~600, and ~1,700 cells,
      respectively. VGluT1+, VGluT2+, and VIAAT+ varicosities respectively represent:
      28%, 41%, and 31% in Mo5; 2%, 49%, and 49% in Mo7; 12%, 42%, and 46% in Amb; and
      4%, 54%, and 42% in Mo12. The Mo5 jaw-closing subdivision shows the highest
      VGluT1+ innervation. Noticeably, the VGluT2+ and VIAAT+ varicosity density in Mo7
      is 5-fold higher than in Mo5 and 10-fold higher than in Amb and Mo12. The high
      density of terminals in Mo7 likely reflects the convergence and integration of
      numerous inputs to motoneurons subserving the wide range of complex behaviors to
      which this nucleus contributes. Also, somatic versus neuropil location of
      varicosities suggests that most of these afferents are integrated in the
      dendritic trees of Mo7 neurons.

PMID- 26224547
TI  - Transferability and additivity of dihedral parameters in polarizable and
      nonpolarizable empirical force fields.
AB  - Recent advances in polarizable force fields have revealed that major
      reparameterization is necessary when the polarization energy is treated
      explicitly. This study is focused on the torsional parameters, which are crucial
      for the accurate description of conformational equilibria in biomolecules. In
      particular, attention is paid to the influence of polarization on the (i)
      transferability of dihedral terms between molecules, (ii) transferability between
      different environments, and (iii) additivity of dihedral energies. To this end,
      three polarizable force fields based on the induced point dipole model designed
      for use in AMBER are tested, including two recent ff02 reparameterizations.
      Attention is paid to the contributions due to short range interactions (1-2, 1-3,
      and 1-4) within the four atoms defining the dihedral angle. The results show that
      when short range 1-2 and 1-3 polarization interactions are omitted, as for
      instance in ff02, the 1-4 polarization contribution is rather small and unlikely
      to improve the description of the torsional energy. Conversely, when screened 1-2
      and 1-3 interactions are included, the polarization contribution is sizeable and
      shows potential to improve the transferability of parameters between different
      molecules and environments as well as the additivity of dihedral terms. However,
      to reproduce intramolecular polarization effects accurately, further fine-tuning
      of the short range damping of polarization is necessary.

PMID- 26224548
TI  - Predatory publishing: Take care that you are not caught in the Open Access net.

PMID- 26224550
TI  - The use of colonic and anorectal high-resolution manometry and its place in
      clinical work and in research.
AB  - BACKGROUND: In the esophagus, high-resolution manometry (HRM) has become a
      standard diagnostic tool in the investigation of suspected motility disorders.
      However, at the opposite end of the digestive tract (i.e., the colon and
      anorectum), the use of HRM still remains in its infancy, with relatively few
      published studies in the scientific literature. Further, the clinical utility of
      those studies that have been performed is largely undetermined. PURPOSE: This
      review assesses all of the HRM studies published to date from both the colon and
      anorectum, explores the catheter types used, and attempts to determine the worth
      of HRM over traditional 'low-resolution' recordings from the same regions.
      Ultimately, this review addresses whether HRM currently provides information that
      will benefit patient diagnosis and treatment.

PMID- 26224549
TI  - The GINA asthma strategy report: what's new for primary care?
AB  - The Global Initiative for Asthma (GINA) was established in 1993 by the World
      Health Organization and National Heart Lung and Blood Institute to develop a
      global strategy for managing and preventing asthma. GINA reports, now funded
      independently through the sale of GINA products, have provided the foundation for
      many national guidelines. They are prepared by international experts from
      primary, secondary and tertiary care, and are annually updated following a review
      of evidence. In 2014, a major revision of the GINA report was published, that
      took into account advances in evidence not only about asthma and its treatment,
      but also about how to improve implementation of evidence-based recommendations in
      clinical practice. This paper summarises key changes relevant to primary care in
      the new GINA report. A noticeable difference is the report's radically different
      approach, now clinically-focussed, with multiple practical tools and flow charts
      to improve its utility for busy frontline clinicians. Key changes in
      recommendations include a new, diagnosis-centred definition of asthma; more
      detail about how to assess current symptom control and future risk; a
      comprehensive approach to tailoring treatment for individual patients; expanded
      indications for commencing inhaled corticosteroids; new recommendations for
      written asthma action plans; a new chapter on diagnosis and initial treatment of
      patients with asthma-COPD overlap syndrome; and a revised approach to diagnosing
      asthma in preschool children. The 2014 GINA report (further updated in 2015)
      moved away from a 'textbook' approach to provide clinicians with up-to-date
      evidence about strategies to control symptoms and minimise asthma risk, in a
      practical, practice-centred format. 

PMID- 26224551
TI  - Transcriptomic analysis of rice in response to iron deficiency and excess.
AB  - BACKGROUND: Iron (Fe) is essential micronutrient for plants and its deficiency as
      well as toxicity is a serious agricultural problem. The mechanisms of Fe
      deficiency are reasonably understood, however our knowledge about plants response
      to excess Fe is limited. Moreover, the regulation of small open reading frames
      (sORFs) in response to abiotic stress has not been reported in rice.
      Understanding the regulation of rice transcriptome in response to Fe deficiency
      and excess could provide bases for developing strategies to breed plants tolerant
      to Fe deficiency as well as excess Fe. RESULTS: We used a novel rice 110 K
      microarray harbouring ~48,620 sORFs to understand the transcriptomic changes that
      occur in response to Fe deficiency and excess. In roots, 36 genes were
      upregulated by excess Fe, of which three were sORFs. In contrast, 1509 genes were
      upregulated by Fe deficiency, of which 90 (6%) were sORFs. Co-expression analysis
      revealed that the expression of some sORFs was positively correlated with the
      genes upregulated by Fe deficiency. In shoots, 50 (19%) of the genes upregulated
      by Fe deficiency and 1076 out of 2480 (43%) genes upregulated by excess Fe were
      sORFs. These results suggest that excess Fe may significantly alter metabolism,
      particularly in shoots. CONCLUSION: These data not only reveal the genes
      regulated by excess Fe, but also suggest that sORFs might play an important role
      in the response of plants to Fe deficiency and excess.

PMID- 26224552
TI  - A candidate factor that interacts with RF2, a restorer of fertility of Lead rice
      type cytoplasmic male sterility in rice.
AB  - BACKGROUND: The pollen function of cytoplasmic male sterile (CMS) plants is often
      recovered by the Restorer of fertility (Rf) gene encoded by the nuclear genome.
      An Rf gene of Lead rice type CMS, Rf2, encodes a small mitochondrial glycine-rich
      protein. RF2 is expected to function by interacting with other proteins, because
      RF2 has no motifs except for glycine-rich domain. FINDINGS: To elucidate the
      protein that interacts with RF2, we performed yeast two-hybrid screening. We
      identified four genes and named RF2-interacting candidate factors (RIF1 to RIF4).
      A study of subcellular localization demonstrated that only RIF2 was targeted to
      mitochondria. A pull-down assay using E. coli-produced recombinant GST-tagged RF2
      and His-tagged RIF2 confirmed that RF2 interacted with RIF2. RIF2 encodes
      ubiquitin domain-containing protein. CONCLUSIONS: These results suggest that RIF2
      is a candidate factor of a fertility restoration complex of RF2.

PMID- 26224553
TI  - Defining the genome structure of 'Tongil' rice, an important cultivar in the
      Korean "Green Revolution".
AB  - BACKGROUND: Tongil (IR667-98-1-2) rice, developed in 1972, is a high-yield rice
      variety derived from a three-way cross between indica and japonica varieties.
      Tongil contributed to the self-sufficiency of staple food production in Korea
      during a period known as the 'Korean Green Revolution'. We analyzed the
      nucleotide-level genome structure of Tongil rice and compared it to those of the
      parental varieties. RESULTS: A total of 17.3 billion Illumina Hiseq reads, 47*
      genome coverage, were generated for Tongil rice. Three parental accessions of
      Tongil rice, two indica types and one japonica type, were also sequenced at
      approximately 30x genome coverage. A total of 2,149,991 SNPs were detected
      between Tongil and Nipponbare varieties. The average SNP frequency of Tongil was
      5.77 per kb. Genome composition was determined based on SNP data by comparing
      Tongil with three parental genome sequences using the sliding window approach.
      Analyses revealed that 91.8% of the Tongil genome originated from the indica
      parents and 7.9% from the japonica parent. Copy numbers of SSR motifs, ORF gene
      distribution throughout the whole genome, gene ontology (GO) annotation, and some
      yield-related QTLs or gene locations were also comparatively analyzed between
      Tongil and parental varieties using sequence-based tools. Each genetic factor was
      transferred from the parents into Tongil rice in amounts that were in proportion
      to the whole genome composition. CONCLUSIONS: Tongil was derived from a three-way
      cross among two indica and one japonica varieties. Defining the genome structure
      of Tongil rice demonstrates that the Tongil genome is derived primarily from the
      indica genome with a small proportion of japonica genome introgression.
      Comparative gene distribution, SSR, GO, and yield-related gene analysis support
      the finding that the Tongil genome is primarily made up of the indica genome.

PMID- 26224554
TI  - Meloidogyne incognita - rice (Oryza sativa) interaction: a new model system to
      study plant-root-knot nematode interactions in monocotyledons.
AB  - BACKGROUND: Plant-parasitic nematodes developed strategies to invade and colonize
      their host plants, including expression of immune suppressors to overcome host
      defenses. Meloidogyne graminicola and M. incognita are root-knot nematode (RKN)
      species reported to damage rice (Oryza sativa L.) cultivated in upland and
      irrigated systems. Despite M. incognita wide host range, study of the molecular
      plant - RKN interaction has been so far limited to a few dicotyledonous model
      plants. The aim of this study was to investigate if the rice cv. Nipponbare
      widely used in rice genomic studies could be used as a suitable monocotyledon
      host plant for studying M. incognita pathogenicity mechanisms. Here we compared
      the ability of M. graminicola and M. incognita to develop and reproduce in
      Nipponbare roots. Next, we tested if RKNs modulates rice immunity-related genes
      expression in galls during infection and express the Mi-crt gene encoding an
      immune suppressor. RESULTS: Root galling, mature females, eggs and newly formed
      J2s nematodes were obtained for both species in rice cultivated in hydroponic
      culture system after 4-5 weeks. Meloidogyne graminicola reproduced at higher
      rates than M. incognita on Nipponbare and the timing of infection was shorter. In
      contrast, the infection characteristics compared by histological analysis were
      similar for both nematode species. Giant cells formed from 2 days after infection
      (DAI) with M. graminicola and from 6 DAI with M. incognita. Real-time PCR (qRT
      PCR) data indicated that RKNs are able to suppress transcription of immune
      regulators genes, such as OsEDS1, OsPAD4 and OsWRKY13 in young galls. Four M.
      incognita reference genes (Mi-eif-3, Mi-GDP-2, Mi-Y45F10D.4, and Mi-actin) were
      selected for normalizing nematode gene expression studies in planta and in pre
      parasitic J2s. Meloidogyne incognita expressed the immune suppressor calreticulin
      gene (Mi-crt) in rice roots all along its infection cycle. CONCLUSION: RKNs
      repress the transcription of key immune regulators in rice, likely in order to
      lower basal defence in newly-formed galls. The calreticulin Mi-CRT can be one of
      the immune-modulator effectors secreted by M. incognita in rice root tissues.
      Together, these data show that rice is a well suited model system to study host-
      M. incognita molecular interactions in monocotyledons.

PMID- 26224555
TI  - A non-radioactive method for small RNA detection by northern blotting.
AB  - BACKGROUND: Small non-coding RNAs are essential regulators of gene expression at
      the transcriptional and posttranscriptional levels. High-throughput sequencing
      has revealed thousands of predicted small RNAs; however, only a few of these have
      been well characterized. Northern blotting is the most convincing method for
      small RNA validation. FINDINGS: In this study, we improved the Northern blot
      method by using biotin-labeled probes. miRNAs and siRNAs derived from both
      Arabidopsis thaliana and Oryza sativa were investigated. The results suggest that
      this improved method is sensitive and efficient, with approximately 5 MUg of
      total RNA being sufficient for detection. Furthermore, long-term storage of
      probes labeled in this manner is more convenient, less contaminative and
      degradative compared with traditional probes. CONCLUSIONS: This protocol is an
      alternative strategy for small RNA detection and represents an efficient means of
      researching small RNAs.

PMID- 26224557
TI  - A fertility restorer gene, Rf4, widely used for hybrid rice breeding encodes a
      pentatricopeptide repeat protein.
AB  - BACKGROUND: Uncontrolled expression of a certain mitochondrial gene often causes
      cytoplasmic male sterility (CMS) in plants. This phenotype is prevented by the
      presence of a fertility restorer (Rf) gene in the nuclear genome. Such CMS/Rf
      systems have been successfully used for breedings of F1 hybrid cultivars. In
      rice, approximately 99% of F1 hybrid cultivars have been developed using a wild
      abortive type of CMS (WA-CMS) and its Rf genes. Recently, a newly identified
      mitochondrial gene, orf352, was reported as a WA-CMS-causing gene. FINDINGS: We
      cloned and functionally characterized Rf4, a major Rf gene for WA-CMS. We
      revealed that Rf4 encoded a pentatricopeptide repeat-containing protein and
      reduced the orf352-containing transcripts, thereby restoring pollen fertility.
      CONCLUSIONS: Through a map-based cloning, we have independently identified an
      allele of a recently reported Rf4 gene and demonstrated that the fertility
      restoration is controlled sporophytically.

PMID- 26224556
TI  - Iron deficiency responses in rice roots.
AB  - Iron (Fe) is an essential element for most living organisms. To acquire sparingly
      soluble Fe from the rhizosphere, rice roots rely on two Fe acquisition pathways.
      The first of these pathways involves Fe(III) chelators specific to graminaceous
      plants, the mugineic acid family phytosiderophores, and the second involves
      absorption of Fe(2+). Key components in this response include enzymes involved in
      the biosynthesis of deoxymugineic acid (OsNAS1, OsNAS2, OsNAAT1, and OsDMAS1),
      the deoxymugineic acid efflux transporter (TOM1), the Fe(III)-deoxymugineic acid
      transporter (OsYSL15), and Fe(2+) transporters (OsIRT1, OsIRT2, and OsNRAMP1). In
      whole roots, these proteins are expressed in a coordinated manner with strong
      transcriptional induction in response to Fe deficiency. Radial transport of Fe to
      xylem and phloem is also mediated by the mugineic acid family phytosiderophores,
      as well as other chelators and their transporters, including Fe(II)-nicotianamine
      transporter (OsYSL2), phenolics efflux transporters (PEZ1 and PEZ2), and citrate
      efflux transporter (OsFRDL1). Among these, OsYSL2 is strongly induced under
      conditions of Fe deficiency. Both transcriptional induction and potential
      feedback repression mediate the expressional regulation of the genes involved in
      Fe uptake and translocation in response to Fe deficiency. The transcription
      factors IDEF1, IDEF2, and OsIRO2 are responsible for transcriptional induction,
      whereas the ubiquitin ligases OsHRZ1 and OsHRZ2, as well as the transcription
      factors OsIRO3 and OsbHLH133, are thought to mediate negative regulation.
      Furthermore, IDEF1 and OsHRZs bind Fe and other metals, and are therefore
      candidate Fe sensors. The interacting functions of these regulators are thought
      to fine tune the expression of proteins involved in Fe uptake and translocation. 

PMID- 26224558
TI  - The roots of future rice harvests.
AB  - Rice production faces the challenge to be enhanced by 50% by year 2030 to meet
      the growth of the population in rice-eating countries. Whereas yield of cereal
      crops tend to reach plateaus and a yield is likely to be deeply affected by
      climate instability and resource scarcity in the coming decades, building rice
      cultivars harboring root systems that can maintain performance by capturing water
      and nutrient resources unevenly distributed is a major breeding target. Taking
      advantage of gathering a community of rice root biologists in a Global Rice
      Science Partnership workshop held in Montpellier, France, we present here the
      recent progresses accomplished in this area and focal points where an
      international network of laboratories should direct their efforts. 

PMID- 26224559
TI  - Genes controlling root development in rice.
AB  - In this review, we report on the recent developments made using both genetics and
      functional genomics approaches in the discovery of genes controlling root
      development in rice. QTL detection in classical biparental mapping populations
      initially enabled the identification of a very large number of large chromosomal
      segments carrying root genes. Two segments with large effects have been
      positionally cloned, allowing the identification of two major genes. One of these
      genes conferred a tolerance to low phosphate content in soil, while the other
      conferred a tolerance to drought by controlling root gravitropism, resulting in
      root system expansion deep in the soil. Findings based on the higher-resolution
      QTL detection offered by the development of association mapping are discussed. In
      parallel with genetics approaches, efforts have been made to screen mutant
      libraries for lines presenting alterations in root development, allowing for the
      identification of several genes that control different steps of root development,
      such as crown root and lateral root initiation and emergence, meristem
      patterning, and the control of root growth. Some of these genes are closely
      phylogenetically related to Arabidopsis genes involved in the control of lateral
      root initiation. This close relationship stresses the conservation among plant
      species of an auxin responsive core gene regulatory network involved in the
      control of post-embryonic root initiation. In addition, we report on several
      genetic regulatory pathways that have been described only in rice. The
      complementarities and the expected convergence of the direct and reverse genetic
      approaches used to decipher the genetic determinants of root development in rice
      are discussed in regards to the high diversity characterizing this species and to
      the adaptations of rice root system architecture to different edaphic
      environments. 

PMID- 26224560
TI  - Rice miR172 induces flowering by suppressing OsIDS1 and SNB, two AP2 genes that
      negatively regulate expression of Ehd1 and florigens.
AB  - BACKGROUND: Rice is a facultative short-day plant that flowers under long days
      (LD) after a lengthy vegetative phase. Although several inhibitors that delay
      flowering have been identified, the process by which rice eventually flowers
      under non-permissive LD conditions is not well understood. RESULTS:
      Overexpression of miR172 reduced flowering time significantly, suggesting its
      role as an inducer. Levels of miR172 increased as plants aged, further supporting
      our findings. Transcripts of SNB and OsIDS1, two members of the AP2 family that
      have the miR172 target site, were reduced in older plants as the level of miR172
      rose. Overexpression of those AP2 genes delayed flowering; overexpression of
      miR172-resistant forms of SNB or OsIDS1 further delayed this process. This
      demonstrated that the AP2 genes function downstream of miR172. Two florigen genes
      -- Hd3a and RFT1 -- and their immediate upstream regulator Ehd1 were suppressed
      in the AP2 overexpression plants. This suggested that the AP2 genes are upstream
      repressors of Ehd1. In phytochrome mutants, miR172d levels were increased whereas
      those of SNB and OsIDS1 were decreased. Thus, it appears that phytochromes
      inhibit miR172d, an AP2 suppresser. CONCLUSIONS: We revealed that miR172d
      developmentally induced flowering via repressing OsIDS1 and SNB, which suppressed
      Ehd1. We also showed that phytochromes negatively regulated miR172.

PMID- 26224561
TI  - Phenotypic analyses of rice lse2 and lse3 mutants that exhibit hyperaccumulation
      of starch in the leaf blades.
AB  - BACKGROUND: To identify genes that potentially regulate the accumulation,
      mobilization, and transport of photoassimilates in rice (Oryza sativa L.) leaves,
      we recently screened a mutant collection of rice by iodine staining to visualize
      leaf starch contents. From this screening, we isolated a rice mutant that
      exhibits hyperaccumulation of starch in leaves and designated it as the Leaf
      Starch Excess 1 (LSE1) mutant. Here, we report two other rice LSE mutants, LSE2
      and LSE3. RESULTS: Unlike lse1 plants, lse2 and lse3 plants displayed retarded
      growth; lse2 showed an extremely dwarf phenotype and rarely survived in paddy
      fields; lse3 showed inhibited growth with pale green leaf blades, low tiller
      numbers, reduced height, and low grain yield. In lse2 and lse3 plants, the mature
      source leaves contained larger amounts of starch and sucrose than those in wild
      type and lse1 plants. Furthermore, microscopic observations of leaf transverse
      sections indicated that hyperaccumulation of starch in chloroplasts of mesophyll
      and bundle sheath cells occurred in lse2 and lse3 plants, while that in vascular
      cells was noticeable only in lse3 leaves. CONCLUSIONS: The distinct phenotypes of
      these three LSE mutants suggest that the LSE2 and LSE3 mutations occur because of
      disruption of novel genes that might be involved in the path of sucrose transport
      from mesophyll cells to phloem sieve elements in rice leaves, the mechanism for
      which has not yet been elucidated.

PMID- 26224562
TI  - Marker-assisted breeding of Indonesia local rice variety Siputeh for semi-dwarf
      phonetype, good grain quality and disease resistance to bacterial blight.
AB  - BACKGROUND: Rice is one of the most important staple food crops in Asia. Since
      the first green revolution beginning in 1960s, high-yield semidwarf modern rice
      varieties have been widely planted; however, traditional rice varieties with tall
      plant type are still grown in many countries due to their good grain quality and
      adaptation to local climate and environment. Siputeh, a local rice variety mainly
      planted in Java and Sumatra islands of Indonesia, produces long grain rice with
      good cooking and eating quality. However, the variety has low yield with tall
      plant type and long growth duration and is highly susceptible to biotic and
      abiotic stress. RESULTS: Siputeh as the recurrent female was crossed with the
      donor line WH421, an elite paternal line of hybrid rice containing the sd1, Wx
      (b), Xa4 and Xa21 genes, followed by backcrossing and self-pollination. TS4, a
      BC3F4 line derived from the breeding program, was obtained through marker
      assisted selection for the sd1, Wx (b), Xa4 and Xa21 loci. TS4 has semi-dwarf
      phenotype and short growth duration. TS4 conferred disease resistance to multiple
      Xanthomonas oryzae pv. oryzae (Xoo) strains collected from different countries
      around the world. TS4 achieved higher grain yield than Siputeh in two field
      trials conducted in Banda Aceh, Indonesia and Lingshui, China, respectively.
      Finally, TS4 has better grain quality than Siputeh in terms of degree of
      chalkiness and amylose content. CONCLUSION: An improved rice line, designed as
      TS4, has been developed to contain semi-dwarf gene sd1, low amylase content gene
      Wx (b) and bacterial light resistance genes Xa4 and Xa21 through marker-assisted
      selection. TS4 has semi-dwarf phenotype with reduced growth duration, produces
      high yield with good grain quality and provides broad-spectrum resistance to Xoo
      strains. The development of TS4 enriches the diversity of local rice varieties
      with high yield potential and good grain quality.

PMID- 26224563
TI  - Socio-economic vulnerability to climate change in the central mountainous region
      of eastern Mexico.
AB  - Climate change effects are expected to be more severe for some segments of
      society than others. In Mexico, climate variability associated with climate
      change has important socio-economic and environmental impacts. From the central
      mountainous region of eastern Veracruz, Mexico, we analyzed data of total annual
      precipitation and mean annual temperature from 26 meteorological stations (1922
      2008) and from General Circulation Models. We developed climate change scenarios
      based on the observed trends with projections to 2025, 2050, 2075, and 2100,
      finding considerable local climate changes with reductions in precipitation of
      over 700 mm and increases in temperature of ~9 degrees C for the year 2100.
      Deforested areas located at windward were considered more vulnerable,
      representing potential risk for natural environments, local communities, and the
      main crops cultivated (sugarcane, coffee, and corn). Socio-economic vulnerability
      is exacerbated in areas where temperature increases and precipitation decreases.

PMID- 26224564
TI  - Biomarker Discovery and Verification of Esophageal Squamous Cell Carcinoma Using
      Integration of SWATH/MRM.
AB  - We propose an efficient integration of SWATH with MRM for biomarker discovery and
      verification when the corresponding ion library is well established. We strictly
      controlled the false positive rate associated with SWATH MS signals and carefully
      selected the target peptides coupled with SWATH and MRM. We collected 10 samples
      of esophageal squamous cell carcinoma (ESCC) tissues paired with tumors and
      adjacent regions and quantified 1758 unique proteins with FDR 1% at protein level
      using SWATH, in which 467 proteins were abundance-dependent with ESCC. After
      carefully evaluating the SWATH MS signals of the up-regulated proteins, we
      selected 120 proteins for MRM verification. MRM analysis of the pooled and
      individual esophageal tissues resulted in 116 proteins that exhibited similar
      abundance response modes to ESCC that were acquired with SWATH. Because the ESCC
      related proteins consisted of a high percentile of secreted proteins, we
      conducted the MRM assay on patient sera that were collected from pre- and
      postoperation. Of the 116 target proteins, 42 were identified in the ESCC sera,
      including 11 with lowered abundances postoperation. Coupling SWATH and MRM is
      thus feasible and efficient for the discovery and verification of cancer-related
      protein biomarkers. 

PMID- 26224565
TI  - Aflibercept a new target therapy in cancer treatment: a review.
AB  - Angiogenesis is the process through which new blood vessels are formed from pre
      existing vessels and is essential for the growth of all solid tumors. Vascular
      endothelial growth factor (VEGF) is a regulator of angiogenesis, which is crucial
      for tumor growth and metastasis. Its inhibition with antiangiogenic drugs is
      thought to improve delivery of chemotherapy through vascular normalization and
      disruption of tumor vasculature. Aflibercept is a recombinant fusion protein of
      the VEGF receptor (VEGFR)1 and VEGFR2 extracellular domains that binds to VEGF-A,
      VEGF-B, placental growth factor (PlGF) 1 and 2. Aflibercept has demonstrated
      preclinical efficacy in different tumor types and exerts its antiangiogenic
      effects through regression of tumor vasculature, remolding of vasculature, and
      inhibition of new tumor vessel growth. This review examines the effects of
      aflibercept on tumor vasculature and on different types of solid tumors, and
      explores the preclinical and clinical benefits of inclusion aflibercept into
      anticancer treatment strategies. 

PMID- 26224567
TI  - Hydrodynamic drag constrains head enlargement for mouthbrooding in cichlids.
AB  - Presumably as an adaptation for mouthbrooding, many cichlid fish species have
      evolved a prominent sexual dimorphism in the adult head. Since the head of fishes
      serves as a bow during locomotion, an evolutionary increase in head volume to
      brood more eggs can trade-off with the hydrodynamic efficiency of swimming. Here,
      the differences between males and females in three-dimensional shape and size of
      the external head surfaces and the effect thereof on drag force during locomotion
      was analysed for the Nile tilapia (Oreochromis niloticus), a maternal
      mouthbrooder. To do so, three-dimensional body surface reconstructions from laser
      scans and computational fluid dynamics simulations were performed. After scaling
      the scanned specimens to post-cranial body volume, in order to theoretically
      equalize propulsive power, the external volume of the head of females was 27%
      larger than that of males (head length + 14%; head width + 9%). These differences
      resulted in an approximate 15% increase in drag force. Yet, hydrodynamics imposed
      important constraints on the adaptation for mouthbrooding as a much more drastic
      drop in swimming efficiency seems avoided by mainly enlarging the head along the
      swimming direction. 

PMID- 26224568
TI  - Cell shape regulation through mechanosensory feedback control.
AB  - Cells undergo controlled changes in morphology in response to intracellular and
      extracellular signals. These changes require a means for sensing and interpreting
      the signalling cues, for generating the forces that act on the cell's physical
      material, and a control system to regulate this process. Experiments on
      Dictyostelium amoebae have shown that force-generating proteins can localize in
      response to external mechanical perturbations. This mechanosensing, and the
      ensuing mechanical feedback, plays an important role in minimizing the effect of
      mechanical disturbances in the course of changes in cell shape, especially during
      cell division, and likely in other contexts, such as during three-dimensional
      migration. Owing to the complexity of the feedback system, which couples
      mechanical and biochemical signals involved in shape regulation, theoretical
      approaches can guide further investigation by providing insights that are
      difficult to decipher experimentally. Here, we present a computational model that
      explains the different mechanosensory and mechanoresponsive behaviours observed
      in Dictyostelium cells. The model features a multiscale description of myosin II
      bipolar thick filament assembly that includes cooperative and force-dependent
      myosin-actin binding, and identifies the feedback mechanisms hidden in the
      observed mechanoresponsive behaviours of Dictyostelium cells during micropipette
      aspiration experiments. These feedbacks provide a mechanistic explanation of
      cellular retraction and hence cell shape regulation. 

PMID- 26224569
TI  - Original antigenic sin with human bocaviruses 1-4.
AB  - Human bocavirus (HBoV) 1 is a widespread parvovirus causing acute respiratory
      disease in young children. In contrast, HBoV2 occurs in the gastrointestinal
      tract and is potentially associated with gastroenteritis, whilst HBoV3 and -4
      infections are less frequent and have not yet been linked with human disease. Due
      to HBoV1 DNA persistence in the nasopharynx, serology has been advocated as a
      better alternative for diagnosing acute infections. In constitutionally healthy
      children, we previously noted that pre-existing HBoV2 immunity in a subsequent
      HBoV1 infection typically resulted in low or non-existent HBoV1-specific antibody
      responses. A phenomenon describing such immunological events among related
      viruses has been known since the 1950s as 'original antigenic sin' (OAS). The aim
      of this study was to characterize this putative OAS phenomenon in a more
      controlled setting. Follow-up sera of 10 rabbit pairs, inoculated twice with
      HBoV1-4 virus-like particles (VLPs) or control antigens, in various combinations,
      were analysed with HBoV1-4 IgG enzyme immunoassays with and without depletion of
      heterotypic HBoV antibodies. There were no significant IgG boosts after the
      second inoculation in either the heterologously or the homologously HBoV
      inoculated rabbits, but a clear increase in cross-reactivity was seen with time.
      We could, however, distinguish a distinct OAS pattern from plain cross
      reactivity: half of the heterologously inoculated rabbits showed IgG patterns
      representative of the OAS hypothesis, in line with our prior results with
      naturally infected children. HBoVs are the first parvoviruses to show the
      possible existence of OAS. Our findings provide new information on HBoV1-4
      immunity and emphasize the complexity of human bocavirus diagnosis. 

PMID- 26224566
TI  - Biomechanics of oral mucosa.
AB  - The prevalence of prosthodontic treatment has been well recognized, and the need
      is continuously increasing with the ageing population. While the oral mucosa
      plays a critical role in the treatment outcome, the associated biomechanics is
      not yet fully understood. Using the literature available, this paper provides a
      critical review on four aspects of mucosal biomechanics, including static,
      dynamic, volumetric and interactive responses, which are interpreted by its
      elasticity, viscosity/permeability, apparent Poisson's ratio and friction
      coefficient, respectively. Both empirical studies and numerical models are
      analysed and compared to gain anatomical and physiological insights. Furthermore,
      the clinical applications of such biomechanical knowledge on the mucosa are
      explored to address some critical concerns, including stimuli for tissue
      remodelling (interstitial hydrostatic pressure), pressure-pain thresholds, tissue
      displaceability and residual bone resorption. Through this review, the state of
      the art in mucosal biomechanics and their clinical implications are discussed for
      future research interests, including clinical applications, computational
      modelling, design optimization and prosthetic fabrication. 

PMID- 26224570
TI  - TWEAK/Fn14 interaction promotes oxidative stress through NADPH oxidase activation
      in macrophages.
AB  - AIM: The interaction between TNF-like weak inducer of apoptosis (TWEAK, Tnfsf12)
      and the receptor, fibroblast growth factor-inducible 14 (Fn14), regulates
      vascular damage through different mechanisms, including inflammation. Oxidative
      stress plays a major role in inflammation and the development of atherosclerosis,
      but the relationship between TWEAK and oxidative stress is, however, poorly
      understood. METHODS AND RESULTS: In this study, we found that TWEAK and Fn14 are
      co-localized with the NADPH subunits, p22phox and Nox2, in human advanced
      atherosclerotic plaques. Using primary human macrophages and a murine macrophage
      cell line, we demonstrate that TWEAK promotes ROS production and enhances NADPH
      oxidase activity. Hence, we show a direct involvement of the TWEAK-Fn14 axis in
      oxidative stress, as genetic silencing of Fn14 or Nox2 abrogates the TWEAK
      induced ROS production. Furthermore, our results point at Rac1 as an upstream
      mediator of TWEAK during oxidative stress. Finally, using an in vivo murine model
      we confirmed the major role of TWEAK in oxidative stress, as genetic silencing of
      Tnfsf12 in an ApoE(-/-) background reduces the number of DHE and 8
      hydroxydeoxyguanosine-positive macrophages by 50%. CONCLUSIONS: Our results
      suggest that TWEAK regulates vascular damage by stimulating ROS production in an
      Nox2-dependent manner. These new insights into the TWEAK/Fn14 axis underline
      their potential use as therapeutic targets in atherosclerosis.

PMID- 26224571
TI  - Micro(RNA) management of smooth muscle cell phenotype and response to vascular
      injury.

PMID- 26224572
TI  - Complex regional pain syndrome.
AB  - Complex regional pain syndrome is a chronic pain condition characterized by
      autonomic and inflammatory features. It occurs acutely in about 7% of patients
      who have limb fractures, limb surgery, or other injuries. Many cases resolve
      within the first year, with a smaller subset progressing to the chronic form.
      This transition is often paralleled by a change from "warm complex regional pain
      syndrome," with inflammatory characteristics dominant, to "cold complex regional
      pain syndrome" in which autonomic features dominate. Multiple peripheral and
      central mechanisms seem to be involved, the relative contributions of which may
      differ between individuals and over time. Possible contributors include
      peripheral and central sensitization, autonomic changes and sympatho-afferent
      coupling, inflammatory and immune alterations, brain changes, and genetic and
      psychological factors. The syndrome is diagnosed purely on the basis of clinical
      signs and symptoms. Effective management of the chronic form of the syndrome is
      often challenging. Few high quality randomized controlled trials are available to
      support the efficacy of the most commonly used interventions. Reviews of
      available randomized trials suggest that physical and occupational therapy
      (including graded motor imagery and mirror therapy), bisphosphonates, calcitonin,
      subanesthetic intravenous ketamine, free radical scavengers, oral
      corticosteroids, and spinal cord stimulation may be effective treatments.
      Multidisciplinary clinical care, which centers around functionally focused
      therapies is recommended. Other interventions are used to facilitate engagement
      in functional therapies and to improve quality of life. 

PMID- 26224573
TI  - Predicting erectile dysfunction in sexually active patients seeking prostate
      health screening: proposal for a multivariable risk stratification.
AB  - To address the severity of erectile dysfunction (ED) in consecutive sexually
      active men seeking a prostate health screening through a multivariable risk
      stratification including comorbidities and lower urinary tract symptoms (LUTS).
      Four hundred and twenty five consecutive subjects with stable sexual relationship
      with normal testosterone levels were enrolled. The International Index of
      Erectile Function (IIEF-5) and the International Prostate Symptom Score (IPSS)
      questionnaires were collected and health-significant comorbidities were scored
      with the Charlson comorbidity index (CCI). All the independent predictors of ED
      were combined to form four different risk categories of ED: low (age?65 years and
      IPSS<8 and CCI=0), intermediate (one of the following: age>65 years, IPSS?8 or
      CCI?1), high (two of the following: age>65 years, IPSS?8 or CCI?1) and very high
      (age >65 years, IPSS?8 and CCI?1). The prevalence of ED increased with increase
      of CCI (chi(2) likelihood ratio: 40.85, P=0.001). The median of the IIEF-5
      significantly reduced with the increase of the CCI (P<0.001) and with the
      worsening of our risk group stratification (P<0.001). At univariate logistic
      regression analysis very high risk was significantly associated with of ED (odds
      ratio: 26.85, P<0.001). Very high-risk group predicted ED with 88% and 56% of
      specificity and sensitivity, respectively. Combining these risk factors through
      our risk stratification may be usefulness in revealing an underling ED. 

PMID- 26224575
TI  - ADHD and the QbTest: Diagnostic Validity of QbTest.
AB  - OBJECTIVE: We assess the diagnostic accuracy of the QbTest, which measures the
      cardinal symptoms of ADHD. METHOD: The study group comprised 182 children (mean
      age about 10 years), of whom 124 had ADHD and 58 had other clinical diagnosis of
      which 81% had ASD. RESULTS: Only QbTest parameters for inattention and
      hyperactivity differentiated between ADHD and other clinical diagnoses at the p
      <= .01 level, not for measures of impulsivity. Sensitivity ranged from 47% to 67%
      and specificity from 72% to 84%. Positive predictive value ranged from 41% to
      86%, and negative predictive value from 43% to 86%. Area under the curve varied
      from .70 to .80. CONCLUSION: The ability of the individual QbTest parameters to
      identify ADHD was moderate. The test's ability to discriminate between ADHD
      subtypes was unsatisfactory.

PMID- 26224574
TI  - Results from an online survey investigating ED patients' insights and treatment
      expectations.
AB  - Data suggest that the currently available therapies for erectile dysfunction (ED)
      do not meet all the patients' and their partners' expectations. The aim was to
      assess ED patients' treatment expectations for a variety of sex- and drug-related
      aspects such as importance of spontaneity, partner satisfaction, ideal onset of
      action and ideal duration of action. A total of n=1124 men with ED and n=410
      healthy men, aged 30-75, participated in this online survey. The ED sample was
      further divided into patients currently undergoing treatment (CTG), patients who
      had been undergoing treatment in the past (PTG) and naive patients (NG). The
      International Index of Erectile Function as well as a mix of study-specific
      questions was used. All groups considered 'maintaining an erection until the
      partner reaches orgasm' the most important aspect regarding erectile function.
      'Being able to please the partner' was considered as the most important aspect
      for a fulfilled sex life. The majority of men (38.1%) further considered an onset
      of action of about 15 min to be desirable. In all, 95.9% further considered a
      duration of action up to 4 h to be desirable whereas approximately 71% of men
      considered a duration of more than 12 h to be too long. It seems that once the
      basic functional aspects related to erectile function have been covered,
      additional benefits such as 'spontaneity' and 'pleasing the partner' become
      important and may be critical for choosing the optimum individual treatment, to
      improve the sexual satisfaction and the adherence to the treatment.

PMID- 26224576
TI  - Lessons Learned From Google Glass: Telemedical Spark or Unfulfilled Promise?
AB  - IMPORTANCE: Wearable devices such as Google Glass could potentially be used in
      the health care setting to expand access and improve quality of care. OBJECTIVE:
      This study aims to assess the demographics of Google Glass users in health care
      and determine the obstacles to using Google Glass by surveying those who are
      known to use the device. DESIGN: A 48-question survey was designed to assess
      demographics of users, technological limitations of Google Glass, and obstacles
      to implementation of the device. SETTING: The physicians surveyed worked in
      various fields of health care, with 50% of the respondents being surgeons.
      PARTICIPANTS: Potential participants were found using an Internet search for
      physicians using Google Glass in their practice. MAIN OUTCOME MEASURES: Outcome
      measures were divided into demographic information of users, technological
      limitations of the device, and administrative obstacles. RESULTS: A 43.6%
      response rate was observed. The majority of users were male, assistant
      professors, in academic hospitals, and in the United States. Numerous
      technological limitations were observed by the majority, including device
      ergonomics, display location, video quality, and audio quality. Patient
      confidentiality and data security were the major concerns among administrative
      obstacles. CONCLUSIONS AND RELEVANCE: Despite the potential of Google Glass,
      numerous obstacles exist that limit its use in health care. While Google Glass
      has been discontinued, the results of this study may be used to guide future
      designs of wearable devices.

PMID- 26224577
TI  - cAMP induces hypertrophy and alters DNA methylation in HL-1 cardiomyocytes.
AB  - cAMP is a highly regulated secondary messenger involved in many biological
      processes. Chronic activation of the cAMP pathway by catecholamines results in
      cardiac hypertrophy and fibrosis; however, the mechanism by which elevated cAMP
      leads to cardiomyopathy is not fully understood. To address this issue, we
      increased intracellular cAMP levels in HL-1 cardiomyocytes, a cell line derived
      from adult mouse atrium, using either the stable cAMP analog N(6),2'-O
      dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) or phosphodiesterase (PDE)
      inhibitors caffeine and theophylline. Elevated cAMP levels increased cell size
      and altered expression levels of cardiac genes and micro-RNAs associated with
      hypertrophic cardiomyopathy (HCM), including Myh6, Myh7, Myh7b, Tnni3, Anp, Bnp,
      Gata4, Mef2c, Mef2d, Nfatc1, miR208a, and miR208b. In addition, DBcAMP altered
      the expression of DNA methyltransferases (Dnmts) and Tet methylcytosine
      dioxygenases (Tets), enzymes that regulate genomic DNA methylation levels.
      Changes in expression of DNA methylation genes induced by elevated cAMP led to
      increased global DNA methylation in HL-1 cells. In contrast, inhibition of DNMT
      activity with 5-azacytidine treatment decreased global DNA methylation levels and
      blocked the increased expression of several HCM genes (Myh7, Gata4, Mef2c,
      Nfatc1, Myh7b, Tnni3, and Bnp) observed with DBcAMP treatment. These results
      demonstrate that cAMP induces cardiomyocyte hypertrophy and altered HCM gene
      expression in vitro and that DNA methylation patterns mediate the upregulation of
      HCM genes induced by cAMP. These data identify a previously unknown mechanism by
      which elevated levels of cAMP lead to increased expression of genes associated
      with cardiomyocyte hypertrophy. 

PMID- 26224578
TI  - Hydrogen sulfide: a novel gaseous signaling molecule and intracellular Ca2+
      regulator in rat parotid acinar cells.
AB  - In addition to nitric oxide (NO), hydrogen sulfide (H2S) is recognized as a
      crucial gaseous messenger that exerts many biological actions in various tissues.
      An attempt was made to assess the roles and underlying mechanisms of both gases
      in isolated rat parotid acinar cells. Ductal cells and some acinar cells were
      found to express NO and H2S synthases. Cevimeline, a muscarinic receptor agonist
      upregulated endothelial NO synthase in parotid tissue. NO and H2S donors
      increased the intracellular Ca(2+) concentration ([Ca(2+)]i). This was not
      affected by inhibitors of phospholipase C and inositol 1,4,5-trisphosphate
      receptors, but was decreased by blockers of ryanodine receptors (RyRs), soluble
      guanylyl cyclase, and protein kinase G. The H2S donor evoked NO production, which
      was decreased by blockade of NO synthases or phosphoinositide 3-kinase or by
      hypotaurine, an H2S scavenger. The H2S donor-induced [Ca(2+)]i increase was
      diminished by a NO scavenger or the NO synthases blocker. These results suggest
      that NO and H2S play important roles in regulating [Ca(2+)]i via soluble guanylyl
      cyclase-cGMP-protein kinase G-RyRs, but not via inositol 1,4,5-trisphosphate
      receptors. The effect of H2S may be partially through NO produced via
      phosphoinositide 3-kinase-Akt-endothelial NO synthase. It was concluded that both
      gases regulate [Ca(2+)]i in a synergistic way, mainly via RyRs in rat parotid
      acinar cells. 

PMID- 26224580
TI  - The impact of statins on biological characteristics of stem cells provides a
      novel explanation for their pleiotropic beneficial and adverse clinical effects.
AB  - Statins reduce atherosclerotic events and cardiovascular mortality. Their side
      effects include memory loss, myopathy, cataract formation, and increased risk of
      diabetes. As cardiovascular mortality relates to plaque instability, which
      depends on the integrity of the fibrous cap, we hypothesize that the inhibition
      of the potential of mesenchymal stem cells (MSCs) to differentiate into
      macrophages would help to explain the long known, but less understood "non-lipid
      associated" or pleiotropic benefit of statins on cardiovascular mortality. In the
      present investigation, MSCs were treated with atorvastatin or pravastatin at
      clinically relevant concentrations and their proliferation, differentiation
      potential, and gene expression profile were assessed. Both types of statins
      reduced the overall growth rate of MSCs. Especially, statins reduced the
      potential of MSCs to differentiate into macrophages while they exhibited no
      direct effect on macrophage function. These findings suggest that the limited
      capacity of MSCs to differentiate into macrophages could possibly result in
      decreased macrophage density within the arterial plaque, reduced inflammation,
      and subsequently enhance plaque stability. This would explain the non-lipid
      associated reduction in cardiovascular events. On a negative side, statins
      impaired the osteogenic and chondrogenic differentiation potential of MSCs and
      increased cell senescence and apoptosis, as indicated by upregulation of p16, p53
      and Caspase 3, 8, and 9. Statins also impaired the expression of DNA repair
      genes, including XRCC4, XRCC6, and Apex1. While the effect on macrophage
      differentiation explains the beneficial side of statins, their impact on other
      biologic properties of stem cells provides a novel explanation for their adverse
      clinical effects. 

PMID- 26224581
TI  - Experimental validation of a nonlinear MUFE model based on cohesive-frictional
      plasticity for trabecular bone.
AB  - Trabecular bone is a porous mineralized tissue playing a major load bearing role
      in the human body. Prediction of age-related and disease-related fractures and
      the behavior of bone implant systems needs a thorough understanding of its
      structure-mechanical property relationships, which can be obtained using
      microcomputed tomography-based finite element modeling. In this study, a
      nonlinear model for trabecular bone as a cohesive-frictional material was
      implemented in a large-scale computational framework and validated by comparison
      of MUFE simulations with experimental tests in uniaxial tension and compression.
      A good correspondence of stiffness and yield points between simulations and
      experiments was found for a wide range of bone volume fraction and degree of
      anisotropy in both tension and compression using a non-calibrated, average set of
      material parameters. These results demonstrate the ability of the model to
      capture the effects leading to failure of bone for three anatomical sites and
      several donors, which may be used to determine the apparent behavior of
      trabecular bone and its evolution with age, disease, and treatment in the future.

PMID- 26224579
TI  - Cellular and molecular processes in ovarian cancer metastasis. A Review in the
      Theme: Cell and Molecular Processes in Cancer Metastasis.
AB  - Ovarian cancer is the most lethal gynecological malignancy. It is usually
      diagnosed at a late stage, with a 5-yr survival rate of <30%. The majority of
      ovarian cancer cases are diagnosed after tumors have widely spread within the
      peritoneal cavity, limiting the effectiveness of debulking surgery and
      chemotherapy. Owing to a substantially lower survival rate at late stages of
      disease than at earlier stages, the major cause of ovarian cancer deaths is
      believed to be therapy-resistant metastasis. Although metastasis plays a crucial
      role in promoting ovarian tumor progression and decreasing patient survival
      rates, the underlying mechanisms of ovarian cancer spread have yet to be
      thoroughly explored. For many years, researchers have believed that ovarian
      cancer metastasizes via a passive mechanism by which ovarian cancer cells are
      shed from the primary tumor and carried by the physiological movement of
      peritoneal fluid to the peritoneum and omentum. However, the recent discovery of
      hematogenous metastasis of ovarian cancer to the omentum via circulating tumor
      cells instigated rethinking of the mode of ovarian cancer metastasis and the
      importance of the "seed-and-soil" hypothesis for ovarian cancer metastasis. In
      this review we discuss the possible mechanisms by which ovarian cancer cells
      metastasize from the primary tumor to the omentum, the cross-talk signaling
      events between ovarian cancer cells and various stromal cells that play crucial
      roles in ovarian cancer metastasis, and the possible clinical implications of
      these findings in the management of this deadly, highly metastatic disease. 

PMID- 26224582
TI  - Quality of life in anterior cruciate ligament-deficient individuals: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Physical and psychological impairments impacting quality of life
      (QOL) are common following ACL reconstruction. Rehabilitation alone is an
      effective alternative to reconstruction for some patients, warranting the
      investigation of QOL in ACL-deficient individuals. PURPOSE: To report and compare
      QOL in ACL-deficient individuals with population norms and ACL-reconstructed
      groups, and investigate relationships between participant characteristics and
      QOL. STUDY DESIGN: Systematic review and meta-analysis. METHODS: We
      systematically identified and methodologically appraised all studies reporting
      QOL in ACL-deficient individuals >=5 years following ACL rupture. Knee-related
      and health-related QOL scores in ACL-deficient cohorts were compared to ACL
      reconstructed groups using a random-effects meta-analysis. Descriptive
      comparisons were made with population norms. RESULTS: Eleven studies reported QOL
      in 473 ACL-deficient individuals, a mean of 10 (range 5-23) years following ACL
      rupture. Eight studies reported knee-related QOL using the Knee injury and
      Osteoarthritis Outcome Score QOL subscale (KOOS-QOL); scores (mean+/-SD) ranging
      from 54+/-17 to 77+/-22 were impaired compared to population norms. Health
      related QOL, measured with the SF-36 domain scores in five studies, was similar
      to population norms, but impaired compared to physically active populations. Meta
      analysis revealed no significant differences in KOOS-QOL (mean difference (95%
      CI) 2.9 (-3.3 to 9.1)) and SF-36 scores (for all SF-36 domains except Vitality)
      between ACL-deficient and ACL-reconstructed groups. CONCLUSIONS: This systematic
      review found impaired knee-related QOL in ACL-deficient individuals >=5 years
      after ACL rupture, compared to population norms. Meta-analysis revealed similar
      knee-related QOL in ACL-deficient and ACL-reconstructed groups, and no difference
      in health-related QOL scores for seven of the eight SF-36 domains.

PMID- 26224583
TI  - Identifying features of 'pathological demand avoidance' using the Diagnostic
      Interview for Social and Communication Disorders (DISCO).
AB  - The term 'pathological demand avoidance' (PDA) was coined by Elizabeth Newson to
      describe children within the autism spectrum who exhibit obsessive resistance to
      everyday demands and requests (Newson et al., Arch Dis Child 88:595-600, 2003).
      Clinical accounts describe avoidance strategies including apparently strategic
      use of distraction or socially shocking behaviour, and obsessive need for
      control, reflected in domineering behaviour to peers and adults. Educational and
      management approaches effective for PDA reportedly differ from those for
      'typical' autism spectrum disorders (ASD), and include novelty, humour and
      flexibility. Identification of PDA in individuals with ASD may have important
      implications for management (Eaton and Banting, J Learn Disabil Offending Behav
      3:150-157, 2012). Despite increasing interest, no clinician-rated instrument for
      PDA has been developed. Here, items relevant to PDA were identified from the
      Diagnostic Interview for Social and Communication Disorder (DISCO) (Wing et al.,
      J Child Psychol Psychiatry 43:307-325, 2002). The most PDA-specific subset of
      relevant DISCO items was selected, based on low endorsement in general across a
      sample of 153 individuals assessed for possible ASD using the DISCO. Having
      selected 11 DISCO PDA items for the measure, a subset of individuals with a high
      number of these features was identified (N = 27). Consistent with Newson's
      descriptions, this high scoring group was characterised by lack of co-operation,
      use of apparently manipulative behaviour, socially shocking behaviour,
      difficulties with other people, anxiety and sudden behavioural changes from
      loving to aggression. All but one case met criteria for an ASD. This study brings
      the field a step closer to a clinician-rated measure of PDA features and
      highlights the need for further elucidation of the PDA phenotype.

PMID- 26224585
TI  - Temporal lobe connects regression and macrocephaly to autism spectrum disorders.
AB  - Interictal electroencephalogram (EEG) abnormalities are frequently associated
      with autism spectrum disorders (ASD), although their relationship with the
      clinical features of ASD, particularly the regressive onset, remains
      controversial. The aim of this study was to investigate whether the
      characteristics of interictal EEG abnormalities might help to distinguish and
      predict definite phenotypes within the heterogeneity of ASD. We reviewed the
      awake and sleep interictal EEGs of 220 individuals with idiopathic ASD, either
      with or without a history of seizures. EEG findings were analyzed with respect to
      a set of clinical variables to explore significant associations. A brain
      morphometry study was also carried out on a subgroup of patients. EEG
      abnormalities were seen in 154/220 individuals (70%) and were mostly focal (p <
      0.01) with an anterior localization (p < 0.001). They were detected more
      frequently during sleep (p < 0.01), and were associated with a regressive onset
      of ASD (p < 0.05), particularly in individuals with focal temporal localization
      (p < 0.05). This association was also stronger in regressive patients with
      concurrent macrocephaly, together with a relative volumetric reduction of the
      right temporal cortex (p < 0.05). Indeed, concurrence of temporal EEG
      abnormalities, regression and macrocephaly might possibly define a distinct
      endophenotype of ASD. EEG-based endophenotypes could be useful to untangle the
      complexity of ASD, helping to establish anatomic or pathophysiologic subtypes of
      the disorder.

PMID- 26224584
TI  - Social skills and psychopathic traits in maltreated adolescents.
AB  - Child maltreatment has frequently been associated with impaired social skills and
      antisocial features, but there are still controversies about the effect of each
      type of maltreatment on social behaviour. The aim of this study was to compare
      the social functioning and psychopathic traits of maltreated adolescents (MTA)
      with a control group (CG) and to investigate what types of maltreatments and
      social skills were associated with psychopathic traits in both groups. The types
      and intensity of maltreatment were evaluated through the Childhood Trauma
      Questionnaire (CTQ) in 107 adolescents, divided into the MTA group (n = 66) and
      non-maltreated youths (n = 41), our CG. The Hare Psychopathy Checklist: Youth
      Version (PCL: YV) and a detailed inventory for evaluation of social skills in
      adolescents were also applied in all individuals. MTA presented more psychopathic
      traits than the CG, in all domains measured by PCL: YV, independently of IQ
      levels and the presence of psychiatric disorders. Interestingly, the groups did
      not differ significantly from each other on indicators of social skills. Multiple
      regression analysis revealed that emotional neglect was the only maltreatment
      subtype significantly associated with psychopathic traits, more specifically with
      the PCL: YV interpersonal factor (F1), and that some social skills (empathy, self
      control and social confidence) were related to specific psychopathic factors. The
      results highlight that emotional neglect may be more detrimental to social
      behaviours than physical and sexual abuse, and that neglected children require
      more specific and careful attention.

PMID- 26224586
TI  - Heterotrimeric G proteins as emerging targets for network based therapy in
      cancer: End of a long futile campaign striking heads of a Hydra.
AB  - Most common diseases, e.g., cancer are driven by not one, but multiple cell
      surface receptors that trigger and sustain a pathologic signaling network. The
      largest fraction of therapeutic agents that target individual receptors/pathways
      eventually fail due to the emergence of compensatory mechanisms that reestablish
      the pathologic network. Recently, a rapidly emerging paradigm has revealed
      GIV/Girdin as a central platform for receptor cross-talk which integrates signals
      downstream of a myriad of cell surface receptors, and modulates several key
      pathways within downstream signaling network, all via non-canonical activation of
      trimeric G proteins. Unlike canonical signal transduction via G proteins, which
      is spatially and temporally restricted, the temporal and spatial features of non
      canonical activation of G protein via GIV is unusually unrestricted.
      Consequently, the GIV?G protein interface serves as a central hub allowing for
      control over several pathways within the pathologic signaling network, all at
      once. The relevance of this new paradigm in cancer and other disease states and
      the pros and cons of targeting the GIV?G protein interface are discussed. 

PMID- 26224587
TI  - Cinacalcet therapy in patients affected by primary hyperparathyroidism associated
      to Multiple Endocrine Neoplasia Syndrome type 1 (MEN1).
AB  - Primary hyperparathyroidism is the main endocrinopathy associated with Multiple
      Endocrine Neoplasia type 1 syndrome. Cinacalcet is a calcimimetic agent licensed
      for the treatment of secondary hyperparathyroidism in patients with end-stage
      renal disease, and for the reduction of marked hypercalcemia in patients with
      parathyroid carcinoma and sporadic hyperparathyroidism requiring surgery but for
      whom parathyroidectomy is contraindicated. It may provide a medical alternative
      for the management of primary hyperparathyroidism in subjects affected by
      Multiple Endocrine Neoplasia type 1. In this longitudinal, intervention study, 33
      MEN1 patients had been enrolled, 10 males and 23 females with a mean age of 40 +/
      11.9 years, range 20-63. Primary hyperparathyroidism was the first clinical
      manifestation in 12 patients. All subjects commenced with Cinacalcet 30 mg/day,
      22 patients starting therapy with calcimimetics as an alternative to surgery, and
      11 patients opting for the medication after the onset of persistent post-surgical
      primary hyperparathyroidism. Duration of follow-up was 12 months. The results of
      this study show significant reductions in serum calcium. The changes in hormonal
      secretions of pituitary and gastroenteropancreatic glands were not significant,
      demonstrating the overall safety of this drug in this disease. Cinacalcet has
      been well tolerated by 28 patients, whereas five individuals complained of
      heartburn and grade 1 nausea, which did not prevent the completion of the study.
      In conclusion, Cinacalcet has resulted to be well tolerated and safe in patients
      with MEN1 syndrome and the calcium homeostasis was stabilized. 

PMID- 26224588
TI  - New genomic somatic amplifications and deletions in papillary thyroid cancer.

PMID- 26224589
TI  - The role of early 18F-FDG PET/CT in therapeutic management and ongoing risk
      stratification of high/intermediate-risk thyroid carcinoma.
AB  - Little is known about the role in ongoing risk stratification of fluorine-18
      fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG
      PET/CT) performed early after radioactive iodine (RAI) ablation in differentiated
      thyroid carcinoma (DTC). The aim of the study is to investigate whether 18F-FDG
      PET/CT performed early after RAI ablation is useful to detect disease and to
      influence therapy and ongoing risk stratification. Patients with
      high/intermediate risk of recurrent DTC were included. 18F-FDG PET/CT scan was
      performed within 6 months after RAI ablation. We confirmed results with other
      imaging techniques, pathology reports, or follow-up. We classified the patient
      response as excellent, acceptable, or incomplete. Modified Hicks criteria were
      used to evaluate clinical impact. We included 81 patients with high/intermediate
      risk of recurrent DTC. Forty-one (50.6%) had positive uptake in 18F-FDG PET/CT,
      with negative (131)I whole-body scan ((131)I WBS). Sensitivity, specificity, and
      diagnostic accuracy of 18F-FDG PET/CT were 92.5, 90.2, and 91.4%, respectively.
      18F-FDG PET/CT results had an impact on therapy in 38.3% of patients. One year
      after initial therapy, 45.7% showed excellent response, 8.6% acceptable response,
      and 45.7% incomplete response. A statistically significant relationship was found
      between negative 18F-FDG PET/CT and excellent response (80 vs. 12.2%, p < 0.001;
      OR 52.8). 18F-FDG PET/CT scan performed early in surveillance of patients with
      high/intermediate-risk thyroid carcinoma provides important additional
      information not available with conventional follow-up methods and had a high
      impact on therapy. A negative 18F-FDG PET/CT predicts an excellent response to
      therapy in the new ongoing risk stratification.

PMID- 26224590
TI  - The early life of a fly glial cell.
AB  - Throughout evolution, glia have key regulatory roles in neural development and
      function. Typically, they control the response to developmental and/or
      pathological signals, thereby affecting neural proliferation, remodeling,
      survival, and regeneration. Such complex biology depends on the plastic features
      of glial cells, but also on the presence of different classes of glial cells,
      hence the importance of understanding the cellular and the molecular mechanisms
      underlying their development. The fly community has made major breakthroughs by
      characterizing the bases of gliogenesis and here we describe the glial lineages
      as well as the glial promoting factor active in the embryo of Drosophila
      melanogaster. WIREs Dev Biol 2016, 5:67-84. doi: 10.1002/wdev.200 For further
      resources related to this article, please visit the WIREs website. 

PMID- 26224592
TI  - ANZJP Weltanschauung.

PMID- 26224591
TI  - Quantitative magnetic resonance imaging of hepatic steatosis: Validation in ex
      vivo human livers.
AB  - Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have
      demonstrated tremendous promise for accurate quantification of hepatic
      triglyceride concentration. These methods quantify the proton density fat
      fraction (PDFF), which reflects the concentration of triglycerides in tissue.
      Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading
      for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with
      the underlying hepatic triglyceride content remained unknown. The aim of this ex
      vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of
      hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic
      resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction, and
      histology as three independent reference standards. A secondary aim was to
      compare the precision of MRI-PDFF relative to biopsy for the quantification of
      hepatic steatosis. MRI-PDFF was prospectively performed at 1.5 Tesla in 13
      explanted human livers. We performed colocalized paired evaluation of liver fat
      content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117) and
      tissue wedges for biochemical triglyceride extraction (n=117), and five core
      biopsies performed in each segment for histologic grading (n=585). Accuracy of
      MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride
      extraction, and histology. Intraobserver agreement, interobserver agreement, and
      repeatability of MRI-PDFF and histologic grading were assessed through Bland
      Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984,
      confidence interval 0.978-0.989) and strong correlation with histology (r=0.850,
      confidence interval 0.791-0.894) and triglyceride extraction (r=0.871, confidence
      interval 0.818-0.909). Intraobserver agreement, interobserver agreement, and
      repeatability showed a significantly smaller variance for MRI-PDFF than for
      histologic steatosis grading (all P<0.001). CONCLUSION: MRI-PDFF is an accurate,
      precise, and reader-independent noninvasive imaging biomarker of liver
      triglyceride content, capable of steatosis quantification over the entire liver.

PMID- 26224593
TI  - Amyotrophic lateral sclerosis presentation of a human T-lymphotropic virus type-1
      myelopathy--insight into pathogenesis.
AB  - A 41-year-old human T-lymphotropic virus type 1-positive woman developed a
      syndrome with upper and lower motor neuron signs sometime after bilateral
      vertebral artery dissections. Over 2 years, she developed a progressive
      myelopathy affecting predominantly the motor system. She had the picture of a
      'person in a barrel' and died from complications. At autopsy, spinal cord
      revealed inflammatory infiltrates and extensive gliosis involving mainly the
      anterior horns. The vertebral arterial dissections may have permitted the entry
      of infected lymphocytes and macrophages, secreting cytokines and
      metalloproteinases, into the medulla progressing to the spinal cord. Few cases
      with pathological correlation have been reported. 

PMID- 26224594
TI  - Evolution of macrolide resistance in Streptococcus pyogenes over 14 years in an
      area of central Italy.
AB  - We evaluated temporal fluctuations in macrolide resistance rates, analysing
      genetic determinants of resistance and clonal evolution in a population of 2744
      S. pyogenes isolates collected in the period 2000-2013. The total resistance rate
      to erythromycin of the isolates was 17.9 %. A maximum of erythromycin resistance
      emerged in 2000 (38.6 %), followed by a significant decrease to 5.2 % in 2012 (P
      < 0.0001). Molecular analysis revealed the presence and co-presence of known
      genetic resistance determinants mefA, mefE, ermTR and ermB, in line with
      phenotypes. PFGE analysis identified genetically related groups in 2000 and 2007
      2008, mainly the MLS and M phenotypes, respectively. The most prevalent emm types
      among a representative subset of resistant isolates were emm2, emm75 and emm77.
      All emm2 and 88.2 % of the strains harbouring the emm75 gene were only recorded
      in M-phenotype strains, whilst all emm77-positive strains had the inducible MLS
      phenotype. The analysed susceptible isolates showed several emm types partially
      shared with resistant ones. Our results suggest that changes in bacterial
      population clonality, rather than horizontal transfer of resistance determinants,
      plays a major epidemiological role in S. pyogenes. Continuous monitoring of
      microbiological epidemiology seems to be crucial for correct and effective
      management of streptococcal infections. 

PMID- 26224595
TI  - New friends for Ago2 in neuronal plasticity.

PMID- 26224596
TI  - Scissors for autolysosome tubules.

PMID- 26224597
TI  - Huntington's disease--the sting in the tail.

PMID- 26224598
TI  - Barriers and Promoters for Enrollment to a Community-Based Tai Chi Program for
      Older, Low-Income, and Ethnically Diverse Adults.
AB  - BACKGROUND: Low-income, ethnically diverse, older adults may be at greater health
      risk owing to their lower activity levels and potential cultural barriers to
      physical activity (PA) programs. To explore the specific barriers and promoters
      to enrollment to a 16-week Tai Chi (TC) program, we interviewed 87 lower
      socioeconomic older adults from multiple ethnic backgrounds before the initiation
      of a TC program. METHOD: Semistructured qualitative focus group interviews were
      conducted with questions focused on themes of barriers and promoters to
      enrollment in a TC program that might or might not be culturally or gender
      related. RESULTS: Important issues emerged that covered six categories.
      Categories included physical and mental health, time of day, socialization,
      program pairing, accessibility, and appropriate leadership/teacher. CONCLUSION:
      This information may have value for tailoring future PA programming in the
      community that could lead to improved health outcomes through better enrollment
      and increased participation in PA and exercise.

PMID- 26224599
TI  - Reproductive and productive performances of Santa Ines ewes submitted to breeding
      in different periods of the Amazonian humid tropical climate.
AB  - The objective of this study was to evaluate the reproductive and productive
      performance of Santa Ines ewes bred at different times of the year in humid
      tropical climate. One hundred and forty-eight Santa Ines ewes were grouped
      according to the time of the year of their breeding season (i.e., mating period)
      (dry/wet, wet, wet/dry, and dry season). The service type was natural mating and
      the ewes and rams were kept together every night for 45 days. Reproductive
      efficiency was assessed by service, pregnancy, lambing, prolificacy, twinning,
      pregnancy loss, weaning, and lamb mortality rates. Ewes were weighed at the
      beginning and at the end of the breeding season and before and after parturition,
      and sequential weighing of the lambs was performed (at birth, 15, 30, 60, and 90
      days). Reproductive efficiency index (number of lambs weaned/total of served
      ewes) and productive efficiency (kg of weaned lamb/kg of served or lambed ewes)
      were calculated. All ewes expressed estrus early in the breeding season; however,
      a higher percentage (53.5 and 7.1 % at 30 and 45 days, respectively) of ewes
      returned to estrus during the wet/dry period. The lower rates (13.9 %) of return
      to estrus at 30 days were during the wet season (P < 0.05). There were no (P >
      0.05) effects of breeding seasons on the remaining reproductive rates. Ewes that
      lambed during the wet/dry transition period weighted less, before (40.5 +/- 2.5
      kg) and after (38.6 +/- 1.6 kg) parturition, than those of other groups (P <
      0.05). Lamb weight at birth did not vary between groups, however, weight at
      weaning was higher (15.6 +/- 2.1 kg) in lambs born during the wet season (P <
      0.05). The reproductive efficiency index was lower (0.66) when the breeding
      season took place during the dry/wet period (P < 0.05). Productive rates were
      significantly higher (0.29 and 0.33 for kg of weaned lamb/kg of served and lambed
      ewes, respectively; P < 0.05) in ewes served in the dry season. The reproductive
      performance of Santa Ines ewes was not significantly influenced by the period of
      the year in which the breeding seasons took place, allowing for four breeding
      seasons a year in the Amazon region. Variations between periods in return to
      estrus rates, weight of ewes close to parturition and lamb weight at weaning
      indicate that climate changes can also affect reproductive rates. 

PMID- 26224600
TI  - Geographical assessment of body measurements and qualitative traits in West
      African cattle.
AB  - A total of 1015 adult cows belonging to nine West African cattle breeds were
      assessed for 16 body measurements and 18 qualitative traits to ascertain the
      existence of geographical patterns of variation. Sampling was carried out in 29
      different provinces of Mali, Burkina Faso and Benin. For body measurements,
      taurine breeds took lower average values than the zebu breeds. Sanga cattle took
      intermediate values. Qualitative traits did not allow to differentiate among
      cattle groups (taurine, zebu or sanga) or breeds. Principal component analysis
      identified two factors explaining 56.4 and 9.2 % of the variance for body
      measurements, respectively. Two correspondence analysis dimensions computed on
      qualitative traits explained a small proportion of the variability (20.8 and 13.5
      %, respectively). Contour plots were constructed using the eigenvalues computed
      for each individual and either factor or dimension identified; confidence regions
      calculated confirmed that body measurements clearly differentiated zebu and
      taurine cattle breeds while qualitative traits did not. Factor 1 was projected on
      a geographical map, using provinces as nodes, to assess breed-free variation for
      body measurements. A pattern of continuous variation from the Sahel area
      southwards was identified. Probably, breeding decisions promoting the crosses
      between zebu-like and taurine cattle are underlying this geographical pattern of
      variation. The implementation of selection strategies aiming at the increase of
      the productivity of native West African taurine cattle breeds while avoiding
      looses in trypanotolerant ability would be highly advisable. 

PMID- 26224601
TI  - Topological insights into the 1/1 diacetyl/water complex gained using a new
      methodological approach.
AB  - The 1/1 diacetyl/water complex is of atmospheric relevance. Previous experimental
      and theoretical studies have focused on two isomeric forms, and geometry
      optimizations were carried out on them. Herein, we propose a six-step
      methodological approach based on topological properties to search for and
      characterize all of the isomeric forms of the 1/1 noncovalent diacetyl/water
      complex: (1) a molecular electrostatic potential (MESP) study to get an overview
      of the V min and V max regions on the molecular surfaces of the separate
      molecules (diacetyl and water); (2) a topological (QTAIM and ELF) study allowing
      thorough characterization of the electron densities (QTAIM) and irreducible ELF
      basins of the separate molecules; (3) full optimization of the predicted
      structures based on the interaction between complementary reaction sites; (4)
      energetic characterization based on a symmetry-adapted perturbation theory (SAPT)
      analysis; (5) topological characterization of the optimized complexes; (6)
      analysis of the complexes in terms of orbital overlaps (natural bond orbitals,
      NBO analysis). Using this approach, in addition to achieving the topological
      characterization of the two isomeric forms already reported, a third possible
      isomer was identified and characterized. Graphical Abstract Topological tools to
      study monohydrated complexes. 

PMID- 26224602
TI  - Modelling of crystal structure of cis-1,2,3,6 and 3,4,5,6-tetrahydrophthalic
      anhydrides using lattice energy calculations.
AB  - Lattice energy calculations using a model potential were performed to model the
      crystal structures of cis-1,2,3,6- and 3,4,5,6-tetrahydrophthalic (THP)
      anhydrides. The optimized molecular models using the DFT method at the B3LYP/6
      31G** level were found consistent with the available experimental evidence and
      allowed all differences observed in crystal packing between cis-1,2,3,6- and
      3,4,5,6-THP anhydrides to be reproduced. Calculations provide evidence for the
      presence of dipole-dipole C=O?C=O intermolecular interactions and support the
      idea that the molecules distort from their ideal geometries, improving packing in
      both crystals. The search for minima in the lattice energy of both crystals
      amongst the more common space groups with Z' = 1, using a simulated annealing
      crystal structure prediction procedure followed by lattice energy minimization
      showed that the observed structure of 3,4,5,6-THP anhydride (Z' = 2) is the
      thermodynamically most stable, and allowed us to justify why 3,4,5,6-THP
      anhydride crystallizes in such a complex structure with 16 molecules in the unit
      cell. The computational model was successful in predicting the second observed
      form at 173 K for cis-1,2,3,6-THP anhydride as a polymorph, and could predict
      several hypothetical structures with Z' = 1 that appear competitive with the
      observed structures. The results of phonon estimates of zero point intermolecular
      vibrational energy and entropy suggest that crystal structures of cis-1,2,3,6-THP
      anhydride cannot be predicted solely on the basis of lattice energy; factors
      other than thermodynamics favor the observed structures.

PMID- 26224603
TI  - Free-radical scavenging by tryptophan and its metabolites through electron
      transfer based processes.
AB  - Free-radical scavenging by tryptophan and eight of its metabolites through
      electron transfer was investigated in aqueous solution at physiological pH, using
      density functional theory and the Marcus theory. A test set of 30 free radicals
      was employed. Thermochemical and kinetic data on the corresponding reactions are
      provided here for the first time. Two different pathways were found to be the
      most important: sequential proton loss electron transfer (SPLET) and sequential
      double proton loss electron transfer (SdPLET). Based on kinetic analyses, it is
      predicted that the tryptophan metabolites kynurenic acid and xanthurenic acid are
      the best free-radical scavengers among the tested compounds; they were estimated
      to be at least 24 and 12 times more efficient than Trolox for scavenging (*)OOH.
      These findings are in line with previous reports suggesting that the antioxidant
      activity that has been attributed to tryptophan is actually due to its
      metabolites, and they demonstrate the particular importance of phenolic
      metabolites to such activity. Graphical Abstract Kynurenic acid (KNA) and
      xanthurenic acid (XNA) are the major contributors to the free-radical scavenging
      activity of tryptophan. 

PMID- 26224604
TI  - The solvatochromism of phenolate betaines: comparing different cavities of a
      polarized continuum model.
AB  - Two variations of the polarized continuum model employing default ("PCM model")
      and SMD radii ("SMD model") were compared for the reproduction of the
      solvatochromic behavior of Reichardt's betaine dye, and of eight other phenolate
      betaines that exhibit a negative, positive or an inverted solvatochromic
      behavior. Molecules were optimized at the CAM B3LYP/6-31+G(d,p) level of theory,
      and transition energies were calculated with the TD-DFT method. The PCM model
      failed to reproduce the negative and the inverted solvachromism of these dyes in
      protic solvents. The SMD model, though not entirely accounting for hydrogen-bond
      effects in small, polar hydroxylic solvents, should be recommended as a better
      alternative for the theoretical simulation of the solvatochromism of phenolate
      betaines in medium to highly polar solvents. Graphical Abstract A comparison of
      two polarized continuum models ("default PCM" and "PCM/SMD") for reproducing the
      solvatochromism of phenolate betaines, with nine examples of negative, positive,
      and inverted behavior. 

PMID- 26224605
TI  - "Maternal High-Fat-Diet Programs Rat Offspring Liver Fatty Acid Metabolism":
      Might Reduced Vitamin D Availability Due to Increases in Maternal Body Fat
      Contribute to This Effect?

PMID- 26224606
TI  - Evaluation of mucositis induced by irinotecan after microbial colonization in
      germ-free mice.
AB  - Mucositis is one of the most debilitating side effects of chemotherapy and some
      previous studies suggest a role for indigenous microbiota in the course of this
      pathology. Therefore, the aim of our study was to evaluate the differences in
      phenotype between germ-free (GF) and conventional (CV) mice, and the role of beta
      glucuronidase-producing bacteria in the development of irinotecan treatment in a
      murine model. After mucositis induction, CV mice showed a significant increase in
      all inflammatory parameters when compared to GF mice. CV animals also showed more
      lesions of the intestinal epithelium, coherent with their higher intestinal
      permeability. The conventionalization of GF animals reversed their phenotype to
      that found in CV mice. In addition, gnotobiotic mice monoassociated with an
      Escherichia coli strain producing beta-glucuronidase showed an increased
      permeability when compared to gnotobiotic mice monoassociated with an E. coli
      strain deleted for the gene encoding beta-glucuronidase, but these did not show
      any differences in the influx of neutrophils, eosinophils or histological
      characteristics. Our data confirmed that components of the gut microbiota are
      involved in the signs of mucositis. Nevertheless, other mechanisms than this
      enzyme are involved in the irinotecan treatment, since the monoassociation was
      not able to restore the entire phenotype observed in the CV animals with
      irinotecan treatment in our murine model.

PMID- 26224607
TI  - Metabolomics based on liquid chromatography with mass spectrometry reveals the
      chemical difference in the stems and roots derived from Ephedra sinica.
AB  - To better understand different traditional uses of the stems (known as Mahuang)
      and roots (known as Mahuanggen) of Ephedra sinica, their chemical difference
      should be investigated. In this study, an ultra-fast liquid chromatography
      coupled with ion trap time-of-flight mass spectrometry untargeted metabolomics
      approach was established to reveal global chemical difference between Mahuang and
      Mahuanggen. Clear separation was observed in scores plots of principal component
      analysis and orthogonal partial least squares-discriminant analysis. Twenty two
      chemical markers responsible for such separation were screened out and
      unambiguously/tentatively characterized. Then chemical markers of
      pharmacologically important ephedrine and pseudoephedrine were absolutely
      quantified using liquid chromatography coupled with tandem mass spectrometry
      under multiple reaction monitoring mode. The results showed that Mahuang was rich
      in ephedrine-type alkaloids, while Mahuanggen was rich in macrocyclic spermine
      alkaloids. Additionally, different types of flavan-3-ols and flavones exist in
      Mahuang and Mahuanggen extracts. This research facilitates a better understanding
      of different traditional uses of Mahuang and Mahuanggen and provides references
      for chemical analysis of other medicinal plants. 

PMID- 26224608
TI  - Biophysical and biochemical markers at 35-37 weeks' gestation in the prediction
      of adverse perinatal outcome.
AB  - OBJECTIVE: To investigate the potential value of biophysical and biochemical
      markers at 35-37 weeks' gestation in the prediction of adverse perinatal outcome.
      METHODS: This was a screening study in 3953 singleton pregnancies at 35-37 weeks'
      gestation. Estimated fetal weight (EFW), uterine artery pulsatility index (UtA
      PI), umbilical artery (UA)-PI, fetal middle cerebral artery (MCA)-PI, mean
      arterial pressure (MAP), serum placental growth factor (PlGF) and soluble fms
      like tyrosine kinase-1 (sFlt-1) were measured. The detection rate (DR) and false
      positive rate (FPR) of screening by each biomarker were estimated for pre
      eclampsia (PE), delivery of small-for-gestational-age (SGA) neonates, Cesarean
      section for fetal distress before or during labor, umbilical arterial cord blood
      pH <= 7.0 or umbilical venous cord blood pH <= 7.1, 5-min Apgar score < 7 and
      admission to the neonatal unit (NNU). RESULTS: Multivariable regression analysis
      demonstrated that significant prediction of PE was provided by PlGF, sFlt-1 and
      MAP, with a DR of 73% at a 10% FPR. Prediction of SGA was provided by EFW, PlGF
      and UtA-PI, with a DR of 63% at a 10% FPR. Prediction of Cesarean section for
      fetal distress before labor was provided by EFW and UA-PI with DR of 100% at 10%
      FPR. Prediction of fetal distress in labor was provided by EFW and sFlt-1, with a
      DR of 15% at a 10% FPR. There were no significant differences between those with
      a normal outcome and those with low cord blood pH, low Apgar score or NNU
      admission for any of the biomarkers assessed. CONCLUSION: At 35-37 weeks'
      gestation biomarkers of impaired placentation and fetal hypoxemia provide good
      prediction of PE, SGA and fetal distress before labor, but poor or no prediction
      of adverse events in labor or after birth.

PMID- 26224609
TI  - Dynamic ligand reactivity in a rhodium pincer complex.
AB  - Ligand cooperativity provides (transition) metal complexes with new reactivities
      in substrate activation and catalytic reactions, but usually the ligand acts as
      an internal (Bronsted) base, while the metal acts as a (Lewis) acid. We describe
      the synthesis and stepwise activation of a new phosphane-pyridine-amide ligand
      PNN(H2) in combination with Rh(I) . The ligand is susceptible to stepwise proton
      and hydride loss from the nitrogen arm (imine formation) and deprotonation at the
      pyridylphosphine arm (dearomatization), giving rise to amine complex 1, amido
      species 2, imine complex 3 and dearomatized compound 4. Complex 4 bears a dual
      mode cooperative PNN' ligand containing both a (nucleophilic) basic methine
      fragment and a reactive (electrophilic) imine moiety. The basic ligand arm
      enables substrate deprotonation while the imine ligand arm enables reversible
      "storage" of the activated (nucleophilic) form of a sulfonamide substrate at the
      ligand. In combination with metal-based reactivity, this allows for the mono
      alkylation of o-toluenesulfonamide with iodomethane. Compounds 1, 3 and 4 are
      structurally characterized. We also report the first structurally characterized
      example of an aminal in the coordination sphere of rhodium, complex 5,
      [Rh(CO)(PNN'')], formed by sequential N?H activation of sulfonamide by the
      dearomatized ligand PNN' and follow-up nucleophilic attack of anionic sulfonamide
      onto the imine fragment. 

PMID- 26224610
TI  - The influence of stem offset and neck shaft angles on the range of motion in
      total hip arthroplasty.
AB  - PURPOSE: To evaluate the influence of stem offset and neck shaft angles on the
      range of motion before component impingement (ROMCI) and bony impingement
      (ROMBI), and the types of impingement in total hip arthroplasty (THA). METHODS:
      Using the computed tomography data of 101 patients who underwent THA, three
      dimensional dynamic motion analysis was performed using a modular implant
      (Kinectiv((r)) stem) that enabled adjustment of offset and leg length
      independently. We defined offset as horizontal offset (HO) and leg length as
      vertical offset (VO), and measured the ROMCI and ROMBI in flexion (Flex),
      internal rotation (Int-R) and external rotation (Ext-R) with the configuration of
      each horizontal/vertical offset. RESULTS: We found that HO lengthening increased
      the ROMCI and ROMBI in Flex and Int-R by delaying bony impingement, although
      excessive lengthening had minimal effect. On the contrary, VO lengthening
      decreased the ROMCI and ROMBI in Flex and ROMCI in Int-R. As for Ext-R, VO
      lengthening had positive effects on the ROMCI and ROMBI, whereas lengthening of
      HO had negative effects on the ROMCI and ROMBI. CONCLUSIONS: We demonstrated that
      the appropriate long offset with a low shaft angle increased the ROM in Flex and
      Int-R, and a high neck shaft angle increased the ROM in Ext-R. We should use
      implants properly in accordance with the types of impingement for avoiding
      dislocations in THA.

PMID- 26224611
TI  - One-stage revision of infected hip arthroplasty: outcome of 39 consecutive hips.
AB  - PURPOSE: There are various options for treating periprosthetic joint infection
      (PJI). Two-stage exchange has traditionally been the gold standard. However, if
      the appropriate surgical intervention is chosen according to a rational
      algorithm, the outcome is similar when using all types of interventions. In an
      observational cohort study, the outcome of patients with PJI after hip
      replacement treated with one-stage revision was analysed. METHODS: All patients
      fulfilling all criteria for one-stage exchange according to the Infectious
      Diseases Society of America (IDSA) guidelines and six without preoperative
      identification of a microorganism were included. Implant removal, debridement and
      cemented or uncemented reimplantations were performed in a single intervention.
      If a cemented device was implanted, commercially available gentamicin cement was
      used in all cases. Antibiotic treatment was administered intravenously for at
      least 2 weeks, followed by oral therapy for a total duration of 3 months.
      Patients had standardised clinical and radiological follow-up visits. RESULTS:
      Between 1996 and 2011, 38 patients (39 hips) were treated with a one-stage
      procedure and followed for at least 2 years. Coagulase-negative staphylococci
      were the most frequent pathogens, and polymicrobial infection was observed in
      five cases. In 25 hips, an uncemented revision stem was implanted, and 37 hips
      received an acetabular reinforcement ring. The mean follow-up was 6.6 (2.0-15.1)
      years. No patient had persistent, recurrent or new infection. There were four
      stem revisions for aseptic loosening. The mean Harris Hip Score was 81 points (26
      99) at the final follow-up. CONCLUSIONS: Excellent cure rate and function seen in
      our study suggest that one-stage exchange is a safe procedure, even without local
      antibiotic treatment, provided that the patient has no sinus tract or severe soft
      tissue damage, no major bone grafting is required and the microorganism is
      susceptible to orally administered agents with high bioavailability.

PMID- 26224612
TI  - Ten to fifteen-year clinical and radiographic follow-up with a third-generation
      cementless stem in a young patient population.
AB  - PURPOSE: Outcome data beyond 11 years of follow-up is not available for the third
      generation Zweymuller femoral stem in combination with a polyethylene bearing. We
      report ten to 15-year results with this total hip arthroplasty (THA) combination
      in a young population. METHODS: A retrospective, observational, non-randomised,
      single-centre, clinical observational study was conducted in which 311 primary
      THAs were performed in 276 patients between 1996 and 2000 using a third
      generation Zweymuller stem. The mean age of the patients at operation was 47.4
      years (range 18-77 years). RESULTS: Stem survival for any reason was 93.5% after
      ten years and 89.6% after 13 years, and the probability of aseptic stem loosening
      was 98.7% at both ten and 13 years. The occurrence of femoral radiolucent lines
      was low, at just 17.2%. Minor femoral osteolysis was identified in 30% of
      patients and was attributed to polyethylene liner wear. Clinical and patient
      satisfaction outcomes were in line with previous investigations, and the rate of
      adverse events was low. CONCLUSIONS: The third-generation Zweymuller stem shows
      good radiographic and clinical results and good longevity, including in the
      younger osteoarthritic patient. The use of low-wear bearings may further reduce
      the rate of osteolysis and wear-related revision in young and active patients.

PMID- 26224613
TI  - A randomized study of autologous conditioned plasma and steroid injections in the
      treatment of lateral epicondylitis.
AB  - PURPOSE: Chronic tendinopathy of lateral epicondyle of the humerus, commonly
      known as "tennis elbow" is one of the most frequent tendinopathies caused by
      recurrent overload of the muscle origins. The aim of the study was to assess the
      effectiveness of treating lateral epicondylitis (LE) with autologous conditioned
      plasma (ACP) and betamethasone injections, and to compare these methods over the
      course of a one year follow-up. METHODS: Patients were randomly placed into one
      of into two groups: 53 were treated with ACP, and 46 with 1 ml betamethasone
      injections and 2 ml of 1 % lignocaine. Both those groups were comparable in terms
      of initial DASH score. RESULTS: After six weeks and six months, the mean DASH
      score was significantly better in the betamethasone group, but was better in ACP
      group after one year. Full recovery (patients with no symptoms) at all time
      points was more common in the betamethasone group. A comparison of grouped DASH
      scores revealed more very good and good results in the ACP group after one year.
      More patients had pain symptoms related to injection in the ACP group than the
      betamethasone group. CONCLUSIONS: ACP therapy of LE allows better results to be
      obtained at 12 months. Betamethasone injections give more rapid improvement, but
      the therapeutic effect is longer lasting in the ACP group.

PMID- 26224614
TI  - Slip abductor pollicis longus suspension tendinoplasty for management of trapezio
      metacarpal joint osteoarthritis.
AB  - PURPOSE: Trapezio-metacarpal (TM) joint arthritis is a common cause of pain and
      functional disability of the hand. The ideal surgical procedure for TM joint
      osteoarthritis is still controversial. The aim of the current study is to assess
      the outcome of complete trapezial excision and abductor pollicis longus tendon
      interposition arthroplasty in the treatment of TM osteoarthritis. METHODS: Twenty
      patients (16 women and 4 men) were prospectively enrolled in the current study
      with average age of 51.5 years (36-64). All patients had complete trapezial
      excision and abductor pollicis longus tendon interposition arthroplasty with
      minimum follow-up of 24 months. RESULTS: At final follow-up there was significant
      improvement as regard pain, range of motion, and functional assessment scores.
      Pre-operative visual analogue scale (VAS) for pain improved from 6.2 (+/-1.54) to
      1.1 (+/-0.97), and the average Quick DASH Score improved from 47.6 (+/-8.81)
      points pre-operatively to 13.6 (+/-5.46) points post-operatively. The mean pre
      operative Buck-Gramcko score system improved from 21 (+/-6.2) points to 41.5 (+/
      7). The average post-operative satisfaction score was 9.1(+/-2.1), with all the
      patients somewhat satisfied and recommending operation to other patients.
      CONCLUSIONS: The total trapeziectomy tendinoplasty with suspension and
      interposition using the abductor pollicis longus is a reliable procedure for the
      treatment of TMJ osteoarthritis, providing satisfactory functional results.

PMID- 26224615
TI  - Description and evaluation of operative deformity correction in calcium
      deficiency rickets in Kaduna, northern Nigeria.
AB  - PURPOSE: Rickets is a recurrent disease worldwide, especially in countries with
      limited resources (Nield et al Am Fam Physician 74(4):619-626, 2006; Thacher et
      al Ann Trop Paediatr 26(1):1-16, 2006). Medical therapy including orally
      administered calcium substitution is shown to improve a patients clinical
      symptoms and positively impact bone deformities, especially in the lower
      extremity. Even though orthopaedic intervention is necessary in a significant
      percentage of patients, few reports exist about operative deformity correction in
      patients wtih rickets. METHODS: We describe our concept of operative treatment by
      single-stage, three-dimensional closing-wedge osteotomies on 45 deformed legs in
      27 patients from the rural area of Kaduna, North Nigeria, with calcium-deficiency
      rickets and evaluate the early results in a 1.5-year follow-up. RESULTS: We found
      a significant improvement in parameters of quality of life, functionality,
      clinical and radiological angulation and angles following the definition of Paley
      et al., with a complication rate of 4 % under 88 osteotomies (Paley et al Orthop
      Clin North Am 25(3):425-65, 1994). CONCLUSION: The described operative therapy
      shows to be sufficient and with satisfactory results in correcting rickets
      related leg deformities under rural circumstances with low availability of
      medical resources.

PMID- 26224616
TI  - Stromal vascular stem cell treatment decreases muscle fibrosis following chronic
      rotator cuff tear.
AB  - PURPOSE: Rotator cuff injuries are associated with atrophy and fat infiltration
      into the muscle, commonly referred to as "fatty degeneration." As the poor
      function of chronically torn muscles may limit recovery after surgical repair,
      there is considerable interest in finding therapies to enhance muscle
      regeneration. Stromal vascular fraction stem cells (SVFCs) can improve muscle
      regeneration in other chronic injury states, and our objective was to evaluate
      the ability of SVFCs to reduce fibrosis and fat accumulation, and enhance muscle
      fibre specific force production after chronic rotator cuff tear. METHODS: Chronic
      supraspinatus tears were induced in adult immunodeficient rats, and repaired one
      month following tear. Rats received vehicle control, or injections of 3 * 10(5)
      or 3 * 10(6) human SVFCs into supraspinatus muscles. RESULTS: Two weeks following
      repair, we detected donor human DNA and protein in SVFC treated muscles. There
      was a 40 % reduction in fibrosis in the treated groups compared to controls (p =
      0.03 for 3 * 10(5), p = 0.04 for 3 * 10(6)), and no differences between groups
      for lipid content or force production were observed. CONCLUSIONS: As there has
      been much interest in the use of stem cell-based therapies in musculoskeletal
      regenerative medicine, the reduction in fibrosis and trend towards an improvement
      in single fiber contractility suggest that SVFCs may be beneficial to enhance the
      treatment and recovery of patients with chronic rotator cuff tears.

PMID- 26224617
TI  - Reliability of the Lisfranc injury radiological classification (Myerson-modified
      Hardcastle classification system).
AB  - PURPOSE: The objective of our study was to assess the reliability of the
      radiological classification system (Myerson-modified Hardcastle Classification
      System) for Lisfranc injury. The classification system is a three-grade ordinal
      scale based on fracture displacement. METHODS: Thirty-nine Lisfranc injury
      radiographs were evaluated by 38 independent observers consisting of consultant
      orthopaedic surgeons (18), orthopaedic surgery residents (17) and consultant
      musculoskeletal radiologists (3) on two separate occasions after receiving
      training in the use of the classification. RESULTS: The intra- and inter-observer
      reliability was assessed using the intraclass correlation coefficient (ICC) and
      found to be excellent. The mean weighted intra- and inter-observer ICCs were 0.94
      (95 % CI 0.89-0.97, p < 0.01) and 0.81 (95 % CI 0.68-0.89, p < 0.01),
      respectively. CONCLUSION: The Myerson-modified Hardcastle classification system
      in our study was shown to be reliable and can be used in outcome studies and
      provide standard terminology among clinicians for Lisfranc injuries.

PMID- 26224618
TI  - Lateral femoral cutaneous nerve injury with the direct anterior approach for
      total hip arthroplasty.
AB  - PURPOSE: Although injury of the lateral femoral cutaneous nerve (LFCN) is a known
      complication after total hip arthroplasty (THA) via the direct anterior approach
      (DAA), the impact of this complication on postoperative quality of life (QOL) is
      unclear. This study aims to investigate the incidence of LFCN injury after DAA
      for THA, and to determine the impact of LFCN injury on QOL and hip function.
      METHODS: We prospectively investigated 122 hips operated upon using the DAA
      regarding the incidence of LFCN injury using self-reported questionnaires, hip
      functional scores such as the Harris Hip Score (HHS) and the Japanese Orthopaedic
      Association (JOA) score, and patient-reported outcomes such as the Western
      Ontario and McMaster Universities Osteoarthritis Index, the Japanese Orthopaedic
      Association Hip disease Evaluation Questionnaire (JHEQ), and the Forgotten Joint
      Score-12 (FJS). RESULTS: LFCN injury was seen in 39 hips (31.9 %). In affected
      hips, the leading symptom was hypo-aesthesia (46.2 %), followed by tingling or
      jolt-like sensation (28.2 %). There was no difference in the HHS and JOA score
      between those with LFCN injury and those without. There was a significant
      difference in the FJS-12 between the two groups (50.9 +/- 25.3 for hips with LFCN
      injury vs 64.3 +/- 25.7 without, p = 0.01). There was a non-significant tendency
      for patients with LFCN injury to have a lower JHEQ than those without (63.6 +/-
      19.6 for hips with LFCN injury vs 70.8 +/- 22.9 without, p = 0.13). CONCLUSIONS:
      The incidence of LFCN injury decreased QOL but not hip function after DAA for
      THA.

PMID- 26224619
TI  - Erratum to: Different thermal conductivity in drilling of cemented compared with
      cementless hip prostheses in the treatment of periprosthetic fractures of the
      proximal femur--an experimental biomechanical analysis.

PMID- 26224621
TI  - Horizontal Gene Transfer.

PMID- 26224620
TI  - Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts
      Attentional Behavior in Mouse.
AB  - Attention is disrupted commonly in psychiatric disorders, yet mechanistic insight
      remains limited. Deficits in this function are associated with dorsal anterior
      cingulate cortex (dACC) excitotoxic lesions and pharmacological disinhibition;
      however, a causal relationship has not been established at the cellular level.
      Moreover, this association has not yet been examined in a genetically tractable
      species such as mice. Here, we reveal that dACC neurons causally contribute to
      attention processing by combining a chemogenetic approach that reversibly
      suppresses neural activity with a translational, touchscreen-based attention task
      in mice. We virally expressed inhibitory hM4Di DREADD (designer receptor
      exclusively activated by a designer drug) in dACC neurons, and examined the
      effects of this inhibitory action with the attention-based five-choice serial
      reaction time task. DREADD inactivation of the dACC neurons during the task
      significantly increased omission and correct response latencies, indicating that
      the neuronal activities of dACC contribute to attention and processing speed.
      Selective inactivation of excitatory neurons in the dACC not only increased
      omission, but also decreased accuracy. The effect of inactivating dACC neurons
      was selective to attention as response control, motivation, and locomotion remain
      normal. This finding suggests that dACC excitatory neurons play a principal role
      in modulating attention to task-relevant stimuli. This study establishes a
      foundation to chemogenetically dissect specific cell-type and circuit mechanisms
      underlying attentional behaviors in a genetically tractable species. 

PMID- 26224623
TI  - Trends in non-metal doping of the SrTiO3 surface: a hybrid density functional
      study.
AB  - Doping of the SrTiO3 surface with non-metal atoms (X = C, N, F, Si, P, S, Cl, Se,
      Br and I) has been considered in a systematic study by performing periodic
      density functional theory calculations using the hybrid HSE06 functional, with
      the objective of improving its photocatalytic activity for water splitting under
      visible light. Our results found that the doping in the top layer of the
      SrTiO3(001) surface is energetically favored. An X (X = C, N and F) atom with a
      relatively small atomic radius tends to substitute the O atom in the TiO2
      terminated surface, while the preferential occupation of the X (X = P, S, Cl, Se
      and Br) atom with larger atomic radius takes place at the O position in the SrO
      terminated surface. X-doped surfaces (X = C, Si and P) show the presence of
      discrete midgap states, which are detrimental to photocatalysis. Due to the
      appearance of surface O 2p states, the band gap of the pure TiO2-terminated
      surface is calculated to be 2.56 eV, which is much narrower than that of bulk
      SrTiO3 (3.4 eV). Our results indicate that the band alignments of N-doped, Br
      doped and I-doped SrTiO3(001) surfaces are well positioned for the feasibility of
      photo-oxidation and photo-reduction of water, which are promising for water
      splitting in the visible light region. 

PMID- 26224622
TI  - Toll-like receptor 4 signaling in neurons of trigeminal ganglion contributes to
      nociception induced by acute pulpitis in rats.
AB  - Pain caused by acute pulpitis (AP) is a common symptom in clinical settings.
      However, its underlying mechanisms have largely remained unknown. Using AP model,
      we demonstrated that dental injury caused severe pulp inflammation with up
      regulated serum IL-1beta. Assessment from head-withdrawal reflex thresholds
      (HWTs) and open-field test demonstrated nociceptive response at 1 day post
      injury. A consistent up-regulation of Toll-like receptor 4 (TLR4) in the
      trigeminal ganglion (TG) ipsilateral to the injured pulp was found; and
      downstream signaling components of TLR4, including MyD88, TRIF and NF-kappaB, and
      cytokines such as TNF-alpha and IL-1beta, were also increased. Retrograde
      labeling indicated that most TLR4 positve neuron in the TG innnervated the pulp
      and TLR4 immunoreactivity was mainly in the medium and small neurons. Double
      labeling showed that the TLR4 expressing neurons in the ipsilateral TG were TRPV1
      and CGRP positive, but IB4 negative. Furthermore, blocking TLR4 by eritoran (TLR4
      antagonist) in TGs of the AP model significantly down-regulated MyD88, TRIF, NF
      kappaB, TNF-alpha and IL-1beta production and behavior of nociceptive response.
      Our findings suggest that TLR4 signaling in TG cells, particularly the
      peptidergic TRPV1 neurons, plays a key role in AP-induced nociception, and
      indicate that TLR4 signaling could be a potential therapeutic target for
      orofacial pain. 

PMID- 26224625
TI  - Comment on: Technical Issues Behind Molecular Monitoring in Chronic Myeloid
      Leukemia.

PMID- 26224626
TI  - Authors' Reply to Crampe and Langabeer: Technical Issues Behind Molecular
      Monitoring in Chronic Myeloid Leukemia.

PMID- 26224624
TI  - Interleukin-35 administration counteracts established murine type 1 diabetes-
      possible involvement of regulatory T cells.
AB  - The anti-inflammatory cytokine IL-35 is produced by regulatory T (Treg) cells to
      suppress autoimmune and inflammatory responses. The role of IL-35 in type 1
      diabetes (T1D) remains to be answered. To elucidate this, we investigated the
      kinetics of Treg cell response in the multiple low dose streptozotocin induced
      (MLDSTZ) T1D model and measured the levels of IL-35 in human T1D patients. We
      found that Treg cells were increased in MLDSTZ mice. However, the Treg cells
      showed a decreased production of anti-inflammatory (IL-10, IL-35, TGF-beta) and
      increased pro-inflammatory (IFN-gamma, IL-2, IL-17) cytokines, indicating a
      phenotypic shift of Treg cells under T1D condition. IL-35 administration
      effectively both prevented development of, and counteracted established MLDSTZ
      T1D, seemingly by induction of Eos expression and IL-35 production in Treg cells,
      thus reversing the phenotypic shift of the Treg cells. IL-35 administration
      reversed established hyperglycemia in NOD mouse model of T1D. Moreover,
      circulating IL-35 levels were decreased in human T1D patients compared to healthy
      controls. These findings suggest that insufficient IL-35 levels play a pivotal
      role in the development of T1D and that treatment with IL-35 should be
      investigated in treatment of T1D and other autoimmune diseases. 

PMID- 26224627
TI  - Murine Double-Minute 2 Homolog Single Nucleotide Polymorphisms 285 and 309 in
      Cervical Carcinogenesis.
AB  - BACKGROUND AND OBJECTIVE: In Caucasians, the MDM2 single nucleotide polymorphism
      (SNP) 285 G>C (rs117039649) neutralizes the effect of 309 T>G (rs2279744), which
      increases MDM2 expression and impairs the p53 pathway. In this study, we examined
      the distribution of these two SNPs in Polish women with squamous cell carcinoma
      (SCC) (n = 379), adenocarcinoma (n = 59) and other cervical tumor types (n = 18).
      METHODS: The polymerase chain reaction-restriction fragment length polymorphism
      technique and DNA sequencing were employed in our study. RESULTS: The P trend
      value calculated for the MDM2 285 G>C polymorphism was statistically significant
      (P trend = 0.016) for SCC. Using logistical regression analysis adjusted for the
      effect of age, pregnancy, oral contraceptive use, tobacco smoking, and menopausal
      status, we observed that the MDM2 285 G>C SNP protected against SCC, with an
      adjusted odd ratio (OR) for the C carriers versus G/G genotype of 0.536 (P =
      0.019). Stratified analyses of MDM2 285 G>C revealed a protective role of the C
      allele against SCC in women with a positive history of oral contraceptive use
      (age-adjusted OR 0.413, P = 0.021) and in premenopausal women (age-adjusted OR
      0.362, P = 0.022). We also found that the 285GG/309GG vs 285GG/309 TT genotype
      increased the risk of SCC (adjusted OR 1.890, P = 0.005). However, the
      285CC/309GG + 285GC/309GG versus 285GG/309GG genotype reduced the risk of SCC
      (adjusted OR 0.311, P = 0.004). CONCLUSION: Our results demonstrate that the MDM2
      285C gene variant and 285CC/309GG + 285GC/309GG genotypes protect against SCC,
      most likely by neutralizing the effect of the 309 T>G SNP. The 285GG/309GG
      genotype increases the risk of SCC possibly due to increased MDM2 expression.

PMID- 26224628
TI  - The MLLE domain of the ubiquitin ligase UBR5 binds to its catalytic domain to
      regulate substrate binding.
AB  - E3 ubiquitin ligases catalyze the transfer of ubiquitin from an E2-conjugating
      enzyme to a substrate. UBR5, homologous to the E6AP C terminus (HECT)-type E3
      ligase, mediates the ubiquitination of proteins involved in translation
      regulation, DNA damage response, and gluconeogenesis. In addition, UBR5 functions
      in a ligase-independent manner by prompting protein/protein interactions without
      ubiquitination of the binding partner. Despite recent functional studies, the
      mechanisms involved in substrate recognition and selective ubiquitination of its
      binding partners remain elusive. The C terminus of UBR5 harbors the HECT
      catalytic domain and an adjacent MLLE domain. MLLE domains mediate
      protein/protein interactions through the binding of a conserved peptide motif,
      termed PAM2. Here, we characterize the binding properties of the UBR5 MLLE domain
      to PAM2 peptides from Paip1 and GW182. The crystal structure with a Paip1 PAM2
      peptide reveals the network of hydrophobic and ionic interactions that drive
      binding. In addition, we identify a novel interaction of the MLLE domain with the
      adjacent HECT domain mediated by a PAM2-like sequence. Our results confirm the
      role of the MLLE domain of UBR5 in substrate recruitment and suggest a potential
      role in regulating UBR5 ligase activity. 

PMID- 26224629
TI  - CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling and Early
      Embryogenesis.
AB  - NF-kappaB essential modulator (NEMO) and cylindromatosis protein (CYLD) are
      intracellular proteins that regulate the NF-kappaB signaling pathway. Although
      mice with either CYLD deficiency or an alteration in the zinc finger domain of
      NEMO (K392R) are born healthy, we found that the combination of these two gene
      defects in double mutant (DM) mice is early embryonic lethal but can be rescued
      by the absence of TNF receptor 1 (TNFR1). Notably, NEMO was not recruited into
      the TNFR1 complex of DM cells, and consequently NF-kappaB induction by TNF was
      severely impaired and DM cells were sensitized to TNF-induced cell death.
      Interestingly, the TNF signaling defects can be fully rescued by reconstitution
      of DM cells with CYLD lacking ubiquitin hydrolase activity but not with CYLD
      mutated in TNF receptor-associated factor 2 (TRAF2) or NEMO binding sites.
      Therefore, our data demonstrate an unexpected non-catalytic function for CYLD as
      an adapter protein between TRAF2 and the NEMO zinc finger that is important for
      TNF-induced NF-kappaB signaling during embryogenesis. 

PMID- 26224630
TI  - Changes in Structural-Mechanical Properties and Degradability of Collagen during
      Aging-associated Modifications.
AB  - During aging, changes occur in the collagen network that contribute to various
      pathological phenotypes in the skeletal, vascular, and pulmonary systems. The aim
      of this study was to investigate the consequences of age-related modifications on
      the mechanical stability and in vitro proteolytic degradation of type I collagen.
      Analyzing mouse tail and bovine bone collagen, we found that collagen at both
      fibril and fiber levels varies in rigidity and Young's modulus due to different
      physiological changes, which correlate with changes in cathepsin K (CatK)
      mediated degradation. A decreased susceptibility to CatK-mediated hydrolysis of
      fibrillar collagen was observed following mineralization and advanced glycation
      end product-associated modification. However, aging of bone increased CatK
      mediated osteoclastic resorption by ~27%, and negligible resorption was observed
      when osteoclasts were cultured on mineral-deficient bone. We observed significant
      differences in the excavations generated by osteoclasts and C-terminal
      telopeptide release during bone resorption under distinct conditions. Our data
      indicate that modification of collagen compromises its biomechanical integrity
      and affects CatK-mediated degradation both in bone and tissue, thus contributing
      to our understanding of extracellular matrix aging. 

PMID- 26224631
TI  - Structural Characterization of Interaction between Human Ubiquitin-specific
      Protease 7 and Immediate-Early Protein ICP0 of Herpes Simplex Virus-1.
AB  - Human ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme that
      prevents protein degradation by removing polyubiquitin chains from its
      substrates. It regulates the stability of a number of human transcription factors
      and tumor suppressors and plays a critical role in the development of several
      types of cancer, including prostate and small cell lung cancer. In addition,
      human USP7 is targeted by several viruses of the Herpesviridae family and is
      required for effective herpesvirus infection. The USP7 C-terminal region (C-USP7)
      contains five ubiquitin-like domains (UBL1-5) that interact with several USP7
      substrates. Although structures of the USP7 C terminus bound to its substrates
      could provide vital information for understanding USP7 substrate specificity, no
      such data has been available to date. In this work we have demonstrated that the
      USP7 ubiquitin-like domains can be studied in isolation by solution NMR
      spectroscopy, and we have determined the structure of the UBL1 domain.
      Furthermore, we have employed NMR and viral plaque assays to probe the
      interaction between the C-USP7 and HSV-1 immediate-early protein ICP0 (infected
      cell protein 0), which is essential for efficient lytic infection and virus
      reactivation from latency. We have shown that depletion of the USP7 in HFF-1
      cells negatively affects the efficiency of HSV-1 lytic infection. We have also
      found that USP7 directly binds ICP0 via its C-terminal UBL1-2 domains and mapped
      the USP7-binding site for ICP0. Therefore, this study represents a first step
      toward understanding the molecular mechanism of C-USP7 specificity toward its
      substrates and may provide the basis for future development of novel antiviral
      and anticancer therapies. 

PMID- 26224632
TI  - Vesicular glutamate transporter 1 orchestrates recruitment of other synaptic
      vesicle cargo proteins during synaptic vesicle recycling.
AB  - A long standing question in synaptic physiology is how neurotransmitter-filled
      vesicles are rebuilt after exocytosis. Among the first steps in this process is
      the endocytic retrieval of the transmembrane proteins that are enriched in
      synaptic vesicles (SVs). At least six types of transmembrane proteins must be
      recovered, but the rules for how this multiple cargo selection is accomplished
      are poorly understood. Among these SV cargos is the vesicular glutamate
      transporter (vGlut). We show here that vGlut1 has a strong influence on the
      kinetics of retrieval of half of the known SV cargos and that specifically
      impairing the endocytosis of vGlut1 in turn slows down other SV cargos,
      demonstrating that cargo retrieval is a collective cargo-driven process. Finally,
      we demonstrate that different cargos can be retrieved in the same synapse with
      different kinetics, suggesting that additional post-endocytic sorting steps
      likely occur in the nerve terminal. 

PMID- 26224633
TI  - Functional and Biochemical Characterization of Hepatitis C Virus (HCV) Particles
      Produced in a Humanized Liver Mouse Model.
AB  - Lipoprotein components are crucial factors for hepatitis C virus (HCV) assembly
      and entry. As hepatoma cells producing cell culture-derived HCV (HCVcc) particles
      are impaired in some aspects of lipoprotein metabolism, it is of upmost interest
      to biochemically and functionally characterize the in vivo produced viral
      particles, particularly regarding how lipoprotein components modulate HCV entry
      by lipid transfer receptors such as scavenger receptor BI (SR-BI). Sera from
      HCVcc-infected liver humanized FRG mice were separated by density gradients.
      Viral subpopulations, termed HCVfrg particles, were characterized for their
      physical properties, apolipoprotein association, and infectivity. We demonstrate
      that, in contrast to the widely spread distribution of apolipoproteins across the
      different HCVcc subpopulations, the most infectious HCVfrg particles are highly
      enriched in apoE, suggesting that such apolipoprotein enrichment plays a role for
      entry of in vivo derived infectious particles likely via usage of apolipoprotein
      receptors. Consistent with this salient feature, we further reveal previously
      undefined functionalities of SR-BI in promoting entry of in vivo produced HCV.
      First, unlike HCVcc, SR-BI is a particularly limiting factor for entry of HCVfrg
      subpopulations of very low density. Second, HCVfrg entry involves SR-BI lipid
      transfer activity but not its capacity to bind to the viral glycoprotein E2. In
      conclusion, we demonstrate that composition and biophysical properties of the
      different subpopulations of in vivo produced HCVfrg particles modulate their
      levels of infectivity and receptor usage, hereby featuring divergences with in
      vitro produced HCVcc particles and highlighting the powerfulness of this in vivo
      model for the functional study of the interplay between HCV and liver components.

PMID- 26224634
TI  - A Hybrid Mechanism for the Synechocystis Arsenate Reductase Revealed by
      Structural Snapshots during Arsenate Reduction.
AB  - Evolution of enzymes plays a crucial role in obtaining new biological functions
      for all life forms. Arsenate reductases (ArsC) are several families of arsenic
      detoxification enzymes that reduce arsenate to arsenite, which can subsequently
      be extruded from cells by specific transporters. Among these, the Synechocystis
      ArsC (SynArsC) is structurally homologous to the well characterized thioredoxin
      (Trx)-coupled ArsC family but requires the glutaredoxin (Grx) system for its
      reactivation, therefore classified as a unique Trx/Grx-hybrid family. The
      detailed catalytic mechanism of SynArsC is unclear and how the "hybrid" mechanism
      evolved remains enigmatic. Herein, we report the molecular mechanism of SynArsC
      by biochemical and structural studies. Our work demonstrates that arsenate
      reduction is carried out via an intramolecular thiol-disulfide cascade similar to
      the Trx-coupled family, whereas the enzyme reactivation step is diverted to the
      coupling of the glutathione-Grx pathway due to the local structural difference.
      The current results support the hypothesis that SynArsC is likely a molecular
      fossil representing an intermediate stage during the evolution of the Trx-coupled
      ArsC family from the low molecular weight protein phosphotyrosine phosphatase
      (LMW-PTPase) family. 

PMID- 26224635
TI  - Substrate-bound structures of benzylsuccinate synthase reveal how toluene is
      activated in anaerobic hydrocarbon degradation.
AB  - Various bacteria perform anaerobic degradation of small hydrocarbons as a source
      of energy and cellular carbon. To activate non-reactive hydrocarbons such as
      toluene, enzymes conjugate these molecules to fumarate in a radical-catalyzed, C
      C bond-forming reaction. We have determined x-ray crystal structures of the
      glycyl radical enzyme that catalyzes the addition of toluene to fumarate,
      benzylsuccinate synthase (BSS), in two oligomeric states with fumarate alone or
      with both substrates. We find that fumarate is secured at the bottom of a long
      active site cavity with toluene bound directly above it. The two substrates adopt
      orientations that appear ideal for radical-mediated C-C bond formation; the
      methyl group of toluene is positioned between fumarate and a cysteine that forms
      a thiyl radical during catalysis, which is in turn adjacent to the glycine that
      serves as a radical storage residue. Toluene is held in place by fumarate on one
      face and tight packing by hydrophobic residues on the other face and sides. These
      hydrophobic residues appear to become ordered, thus encapsulating toluene, only
      in the presence of BSSbeta, a small protein subunit that forms a tight complex
      with BSSalpha, the catalytic subunit. Enzymes related to BSS are able to
      metabolize a wide range of hydrocarbons through attachment to fumarate. Using our
      structures as a guide, we have constructed homology models of several of these "X
      succinate synthases" and determined conservation patterns that will be useful in
      understanding the basis for catalysis and specificity in this family of enzymes. 

PMID- 26224636
TI  - ETS-related transcription factors ETV4 and ETV5 are involved in proliferation and
      induction of differentiation-associated genes in embryonic stem (ES) cells.
AB  - The pluripotency and self-renewal capacity of embryonic stem (ES) cells is
      regulated by several transcription factors. Here, we show that the ETS-related
      transcription factors Etv4 and Etv5 (Etv4/5) are specifically expressed in
      undifferentiated ES cells, and suppression of Oct3/4 results in down-regulation
      of Etv4/5. Simultaneous deletion of Etv4 and Etv5 (Etv4/5 double knock-out (dKO))
      in ES cells resulted in a flat, epithelial cell-like appearance, whereas the
      morphology changed into compact colonies in a 2i medium (containing two
      inhibitors for GSK3 and MEK/ERK). Expression levels of self-renewal marker genes,
      including Oct3/4 and Nanog, were similar between wild-type and dKO ES cells,
      whereas proliferation of Etv4/5 dKO ES cells was decreased with overexpression of
      cyclin-dependent kinase inhibitors (p16/p19, p15, and p57). A differentiation
      assay revealed that the embryoid bodies derived from Etv4/5 dKO ES cells were
      smaller than the control, and expression of ectoderm marker genes, including
      Fgf5, Sox1, and Pax3, was not induced in dKO-derived embryoid bodies. Microarray
      analysis demonstrated that stem cell-related genes, including Tcf15, Gbx2, Lrh1,
      Zic3, and Baf60c, were significantly repressed in Etv4/5 dKO ES cells. The
      artificial expression of Etv4 and/or Etv5 in Etv4/5 dKO ES cells induced re
      expression of Tcf15 and Gbx2. These results indicate that Etv4 and Etv5,
      potentially through regulation of Gbx2 and Tcf15, are involved in the ES cell
      proliferation and induction of differentiation-associated genes in ES cells. 

PMID- 26224638
TI  - Circulating chromosome 19 miRNA cluster microRNAs in pregnant women with severe
      pre-eclampsia.
AB  - AIM: To clarify the association between circulating chromosome 19 miRNA cluster
      (C19MC) microRNAs in maternal plasma and severe pre-eclampsia. METHOD: Maternal
      blood samples (7 mL) at 27-34 weeks of gestation were obtained from 20 pregnant
      women with severe pre-eclampsia (sPE group) and from 20 uncomplicated pregnant
      women (NP group). Twenty cases of severe pre-eclampsia were classified into late
      onset (sPELO group; n = 14) and early onset (sPEEO group; n = 6). Plasma
      concentration of C19MC microRNAs (miR-518b, -1323, -516b, -516a-5p, -525-5p, -515
      5p, -520 h, -520a-5p, -519d and -526b) was measured on quantitative real-time
      reverse transcription-polymerase chain reaction. RESULTS: The circulating levels
      of all 10 C19MC microRNAs in maternal plasma were significantly increased in the
      sPE group compared with the NP group. Plasma concentration of all 10 C19MC
      microRNAs tested was significantly increased in the sPEEO group compared with the
      NP group, while plasma concentration of nine miRNAs, except for miR-519d, was
      significantly increased in the sPELO group compared with the NP group. Of the 10
      C19MC microRNAs measured, plasma concentration of eight miRNAs, except for miR
      518b and miR-519d, was significantly increased in the sPEEO group compared with
      the sPELO group. CONCLUSIONS: Increased levels of C19MC microRNAs in maternal
      plasma are a characteristic phenomenon of established severe pre-eclampsia, and
      it has been shown for the first time that the upregulation of C19MC miRNAs
      occurred as a consequence of, not in advance of, the onset of pre-eclampsia.

PMID- 26224637
TI  - Evidence that the DNA mismatch repair system removes 1-nucleotide Okazaki
      fragment flaps.
AB  - The DNA mismatch repair (MMR) system plays a major role in promoting genome
      stability and suppressing carcinogenesis. In this work, we investigated whether
      the MMR system is involved in Okazaki fragment maturation. We found that in the
      yeast Saccharomyces cerevisiae, the MMR system and the flap endonuclease Rad27
      act in overlapping pathways that protect the nuclear genome from 1-bp insertions.
      In addition, we determined that purified yeast and human MutSalpha proteins
      recognize 1-nucleotide DNA and RNA flaps. In reconstituted human systems,
      MutSalpha, proliferating cell nuclear antigen, and replication factor C activate
      MutLalpha endonuclease to remove the flaps. ATPase and endonuclease mutants of
      MutLalpha are defective in the flap removal. These results suggest that the MMR
      system contributes to the removal of 1-nucleotide Okazaki fragment flaps. 

PMID- 26224639
TI  - The association between tumor necrosis factor-alpha-308 G/A polymorphism and risk
      for vitiligo: a meta-analysis.
AB  - BACKGROUND: The contribution of tumor necrosis factor-alpha (TNF-alpha)-308 G/A
      gene polymorphism (rs1800629) to risk for vitiligo is subject to controversy.
      OBJECTIVES: The fundamental purpose of the present meta-analysis was to
      investigate large-scale evidence to determine the overall association between TNF
      alpha-308 G/A polymorphism and susceptibility to vitiligo. METHODS: A literature
      search of the PubMed, EMBASE, Web of Science, and China National Knowledge
      Infrastructure (CNKI) databases was conducted to identify all studies referring
      to an association between TNF-alpha-308 G/A polymorphism and vitiligo published
      to June 1, 2014. The principal outcome measure for evaluating the strength of the
      association was the crude odds ratio (OR) along with the corresponding 95%
      confidence interval (CI). Data were extracted, and statistical analyses were
      implemented using stata Version 12.0. RESULTS: Data for a total of 1505 vitiligo
      cases and 2253 controls from five case-control studies concentrating on the
      association between TNF-alpha-308 G/A polymorphism and vitiligo were included in
      this meta-analysis. Combined analysis revealed there to be no association between
      this polymorphism and susceptibility to vitiligo in five genetic models under
      random-effects models. A subgroup analysis by clinical type also demonstrated the
      absence of any association between TNF-alpha-308 G/A polymorphism and generalized
      vitiligo. However, a significant association was detected in the miscellaneous
      subgroup under the dominant model (fixed-effects model: OR 5.69, 95% CI 4.70
      6.88; P = 0.000) and overdominant model (random-effects model: OR 5.24, 95% CI
      2.26-12.17; P = 0.000). CONCLUSIONS: This meta-analysis indicates that TNF-alpha
      308 G/A polymorphism is not a genetic risk factor for vitiligo.

PMID- 26224640
TI  - Intrafamilial clinical variability in individuals carrying the CHCHD10 mutation
      Gly66Val.
AB  - OBJECTIVES: Mutations in the CHCHD10 gene, which encodes a mitochondrially
      targeted protein, have emerged as an important cause of motor neuron disease and
      frontotemporal lobar degeneration. The aim of this study was to assess the
      clinical variability in a large family carrying the p.Gly66Val mutation of the
      CHCHD10 gene. This mutation has recently been reported to cause late-onset spinal
      muscular atrophy (SMAJ) or sensorimotor axonal Charcot-Marie-Tooth neuropathy
      (CMT2) in the Finnish population. MATERIALS AND METHODS: Nine affected members of
      an extended Finnish pedigree were included in the study. Detailed clinical and
      neurophysiological examinations were performed. The CHCHD10 p.Gly66Val mutation
      was examined by Sanger sequencing. RESULTS: The heterozygous p.Gly66Val mutation
      was present in all affected individuals from whom a DNA sample was available. The
      clinical phenotype varied from proximal sensorimotor neuropathy to spinal
      muscular atrophy and in one case resembled motor neuron disease ALS at its early
      stages. The age of onset varied from 30 to 73 years. CONCLUSIONS: Our data
      demonstrate that even within the same family, the p.Gly66Val variant can cause
      variable phenotypes ranging from CMT2-type axonal neuropathy to spinal muscular
      atrophy, which may also present as an ALS-like disease. The spectrum of CHCHD10
      related neuromuscular disease has widened rapidly, and we recommend keeping the
      threshold for genetic testing low particularly when dominant inheritance or
      mitochondrial pathology is present.

PMID- 26224641
TI  - PTEN Overexpression Cooperates With Lithium to Reduce the Malignancy and to
      Increase Cell Death by Apoptosis via PI3K/Akt Suppression in Colorectal Cancer
      Cells.
AB  - Lithium is a well-established non-competitive inhibitor of glycogen synthase
      kinase-3beta (GSK-3beta), a kinase that is involved in several cellular processes
      related to cancer progression. GSK-3beta is regulated upstream by PI3K/Akt, which
      is negatively modulated by PTEN. The role that lithium plays in cancer is
      controversial because lithium can activate or inhibit survival signaling pathways
      depending on the cell type. In this study, we analyzed the mechanisms by which
      lithium can modulate events related to colorectal cancer (CRC) progression and
      evaluated the role that survival signaling pathways such as PI3K/Akt and PTEN
      play in this context. We show that the administration of lithium decreased the
      proliferative potential of CRC cells in a GSK-3beta-independent manner but
      induced the accumulation of cells in G2/M phase. Furthermore, high doses of
      lithium increased apoptosis, which was accompanied by decreased proteins levels
      of Akt and PTEN. Then, cells that were induced to overexpress PTEN were treated
      with lithium; we observed that low doses of lithium strongly increased apoptosis.
      Additionally, PTEN overexpression reduced proliferation, but this effect was
      minor compared with that in cells treated with lithium alone. Furthermore, we
      demonstrated that PTEN overexpression and lithium treatment separately reduced
      cell migration, colony formation, and invasion, and these effects were enhanced
      when lithium treatment and PTEN overexpression were combined. In conclusion, our
      findings indicate that PTEN overexpression and lithium treatment cooperate to
      reduce the malignancy of CRC cells and highlight lithium and PTEN as potential
      candidates for studies to identify new therapeutic approaches for CRC treatment.

PMID- 26224642
TI  - Capsule Studies Performed in a Tertiary Care Center Versus Community Referrals
      Prior to Single-Balloon Enteroscopy: Does It Matter?
AB  - BACKGROUND AND AIMS: Within the community, patients with positive capsule
      endoscopy (CE) are often referred to centers performing balloon-assisted
      enteroscopy. There is limited data evaluating the concordance and
      diagnostic/therapeutic yield of CE performed in the community versus CE conducted
      at institutions experienced with enteroscopy. The primary aim of this
      retrospective study was to evaluate the concordance between CE and SBE after CE
      was performed either in the community or at our tertiary care center. METHODS: A
      total of 141 patients were analyzed after selecting patients undergoing
      evaluation of obscure GI bleeding from January 2010 to May 2014. Forty-seven CE
      were performed inside and the remaining 94 CE were performed at outside
      institutions prior to single-balloon enteroscopy at our institution. Agreement
      beyond chance was evaluated using kappa coefficient. A p value <5% was considered
      significant. RESULTS: The most frequent findings on CE were vascular lesions in
      39 patients (41.5%) within the referral group and 23 within inside patients
      (48.9%), followed by active bleeding/clots in 23 patients (24.5%) and in 14
      patients (29.8%) respectively. There was a fair degree of concordance in the
      referral group for vascular lesions 0.23 (0.03-0.42) compared to a good degree in
      the inside group 0.65 (0.44-0.87). Fair agreement was found looking at ulcers
      within the referral group 0.29 (0.06-0.65) compared to a moderate agreement in
      the inside group 0.55 (0.17-0.94). CONCLUSIONS: Degree of concordance for
      vascular lesions and ulcers was significantly higher for patients undergoing CE
      at our institution compared to those referred from the community. Patients
      referred to tertiary care centers for balloon-assisted enteroscopy may benefit
      from advanced endoscopists re-reading the capsule findings or even potentially
      repeating CE in hemodynamically stable patients if the study is not available.

PMID- 26224643
TI  - Evaluation of experimental methods for nitric oxide release from cardiovascular
      implants; bypass grafts as an exemplar.
AB  - BACKGROUND: There is a great potential for nitric oxide (NO) eluting biomaterials
      in biomedical applications. These include the development of cardiovascular
      implants, wound healing products, or applications in cancer and respiratory
      therapy. While the potential of these materials as a therapy is becoming clearer,
      the real-time monitoring of NO is not easy and the success in the development of
      such materials depends on the accurate quantification of NO release. METHOD: To
      emphasize on the importance of a measurement technique on the outcome of an
      experiment, we compared total NO released from S-nitroso-N-acetyl-d-penicillamine
      (SNAP) incorporated nanocomposite polymer in the form of bypass grafts under
      simulated physiological conditions using amperometric and chemiluminescence
      techniques. RESULTS: We found that the total amount of NO measured by the
      amperometric technique was 35.8% of the theoretical amount. Similarly, on
      measuring NO release from the bypass grafts, we demonstrated that the
      chemiluminesence technique detected NO at a relatively higher level. CONCLUSIONS:
      The results of this study clearly demonstrate the relative difference between
      analysis techniques for accurate NO detection that can be applied to distinct
      experimental models associated with NO-eluting cardiovascular implants.

PMID- 26224645
TI  - Immunodeficiency and severe susceptibility to bacterial infection associated with
      a loss-of-function homozygous mutation of MKL1.
AB  - Megakaryoblastic leukemia 1 (MKL1), also known as MAL or myocardin-related
      transcription factor A (MRTF-A), is a coactivator of serum response factor, which
      regulates transcription of actin and actin cytoskeleton-related genes. MKL1 is
      known to be important for megakaryocyte differentiation and function in mice, but
      its role in immune cells is unexplored. Here we report a patient with a
      homozygous nonsense mutation in the MKL1 gene resulting in immunodeficiency
      characterized predominantly by susceptibility to severe bacterial infection. We
      show that loss of MKL1 protein expression causes a dramatic loss of filamentous
      actin (F-actin) content in lymphoid and myeloid lineage immune cells and
      widespread cytoskeletal dysfunction. MKL1-deficient neutrophils displayed reduced
      phagocytosis and almost complete abrogation of migration in vitro. Similarly,
      primary dendritic cells were unable to spread normally or to form podosomes.
      Silencing of MKL1 in myeloid cell lines revealed that F-actin assembly was
      abrogated through reduction of globular actin (G-actin) levels and disturbed
      expression of multiple actin-regulating genes. Impaired migration of these cells
      was associated with failure of uropod retraction likely due to altered
      contractility and adhesion, evidenced by reduced expression of the myosin light
      chain 9 (MYL9) component of myosin II complex and overexpression of CD11b
      integrin. Together, our results show that MKL1 is a nonredundant regulator of
      cytoskeleton-associated functions in immune cells and fibroblasts and that its
      depletion underlies a novel human primary immunodeficiency. 

PMID- 26224644
TI  - Fifteen years of genomewide scans for selection: trends, lessons and unaddressed
      genetic sources of complication.
AB  - Genomewide scans for natural selection (GWSS) have become increasingly common
      over the last 15 years due to increased availability of genome-scale genetic
      data. Here, we report a representative survey of GWSS from 1999 to present and
      find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while
      from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating
      increased focus on nonmodel organisms; (ii) the large majority of GWSS
      incorporate interpopulation or interspecific comparisons using, for example
      F(ST), cross-population extended haplotype homozygosity or the ratio of
      nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of
      directional selection rather than other modes such as balancing selection; and
      (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers
      to dense SNP data. A survey of GWSS meant to identify loci positively selected in
      response to severe hypoxic conditions support an approach to GWSS in which a list
      of a priori candidate genes based on potential selective pressures are used to
      filter the list of significant hits a posteriori. We also discuss four frequently
      ignored determinants of genomic heterogeneity that complicate GWSS: mutation,
      recombination, selection and the genetic architecture of adaptive traits. We
      recommend that GWSS methodology should better incorporate aspects of genomewide
      heterogeneity using empirical estimates of relevant parameters and/or realistic,
      whole-chromosome simulations to improve interpretation of GWSS results. Finally,
      we argue that knowledge of potential selective agents improves interpretation of
      GWSS results and that new methods focused on correlations between environmental
      variables and genetic variation can help automate this approach.

PMID- 26224646
TI  - Effects of eltrombopag on platelet count and platelet activation in Wiskott
      Aldrich syndrome/X-linked thrombocytopenia.
AB  - Because Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT)
      patients have microthrombocytopenia, hemorrhage is a major problem. We asked
      whether eltrombopag, a thrombopoietic agent, would increase platelet counts,
      improve platelet activation, and/or reduce bleeding in WAS/XLT patients. In 9
      WAS/XLT patients and 8 age-matched healthy controls, platelet activation was
      assessed by whole blood flow cytometry. Agonist-induced platelet surface
      activated glycoprotein (GP) IIb-IIIa and P-selectin in WAS/XLT patients were
      proportional to platelet size and therefore decreased compared with controls. In
      contrast, annexin V binding showed no differences between WAS/XLT and controls.
      Eltrombopag treatment resulted in an increased platelet count in 5 out of 8
      patients. Among responders to eltrombopag, immature platelet fraction in 3
      WAS/XLT patients was significantly less increased compared with 7 pediatric
      chronic immune thrombocytopenia (ITP) patients. Platelet activation did not
      improve in 3 WAS/XLT patients whose platelet count improved on eltrombopag. IN
      CONCLUSION: (1) the reduced platelet activation observed in WAS/XLT is primarily
      due to the microthrombocytopenia; and (2) although the eltrombopag-induced
      increase in platelet production in WAS/XLT is less than in ITP, eltrombopag has
      beneficial effects on platelet count but not platelet activation in the majority
      of WAS/XLT patients. This trial was registered at www.clinicaltrials.gov as
      #NCT00909363.

PMID- 26224647
TI  - Transmembrane TNF-alpha preferentially expressed by leukemia stem cells and
      blasts is a potent target for antibody therapy.
AB  - To design an effective antibody therapy to improve clinical outcomes in leukemia,
      the identification of novel cell surface antigens is needed. Herein, we
      demonstrate a role for transmembrane tumor necrosis factor-alpha (tmTNF-alpha) in
      leukemia. To characterize tmTNF-alpha expression in acute leukemia (AL), normal
      hematopoietic cells, and nonhematopoietic tissues, we used a monoclonal antibody,
      termed C1, which specifically recognizes the tmTNF-alpha domain. We found that
      tmTNF-alpha was preferentially expressed by AL and leukemia stem cells (LSCs).
      More abundant expression correlated with poor risk stratification, extramedullary
      infiltration, and adverse clinical parameters. Moreover, knockdown of tmTNF
      alpha(+) expression rendered leukemia cells more sensitive to chemotherapy in
      vitro and delayed regeneration of leukemia in NOD-SCID mice. Targeting tmTNF
      alpha by C1 resulted in leukemia cell killing via antibody-dependent cell
      mediated and complement-dependent cytotoxicity in vitro and inhibited leukemia
      cell growth in vivo while simultaneously sparing normal hematopoietic cells.
      Notably, C1 administration impaired the regeneration of leukemia in secondary
      serial transplantation into NOD-SCID mice. In conclusion, tmTNF-alpha has a
      favorable AL- and LSC-associated expression profile and is important for the
      survival and proliferation of these cells. C1-mediated targeting shows potent
      anti-LSC activity, indicating that tmTNF-alpha represents a novel target antigen
      in AL. 

PMID- 26224648
TI  - Folic acid attenuates the effects of amyloid beta oligomers on DNA methylation in
      neuronal cells.
AB  - PURPOSE: Alzheimer's disease (AD) is a highly prevalent type of dementia. The
      epigenetic mechanism of gene methylation provides a putative link between
      nutrition, one-carbon metabolism, and disease progression because folate
      deficiency may cause hypomethylation of promoter regions in AD-relevant genes. We
      hypothesized that folic acid supplementation may protect neuron cells from
      amyloid beta (Abeta) oligomer-induced toxicity by modulating DNA methylation of
      APP and PS1 in AD models. METHODS: Primary hippocampal neuronal cells and
      hippocampal HT-22 cells were incubated for 24 h with a combination of folic acid
      and either Abeta oligomers or vehicle and were then incubated for 72 h with
      various concentrations of folic acid. AD transgenic mice were fed either folate
      deficient or control diets and gavaged daily with various doses of folic acid (0
      or 600 MUg/kg). DNA methyltransferase (DNMT) activity, cell viability,
      methylation potential of cells, APP and PS1 expression, and the methylation of
      the respective promoters were determined. RESULTS: Abeta oligomers lowered DNMT
      activity, increased PS1 and APP expression, and decreased cell viability. Folic
      acid dose-dependently stimulated methylation potential and DNMT activity, altered
      PS1 and APP promoter methylation, decreased PS1 and APP expression, and partially
      preserved cell viability. Folic acid increased PS1 and APP promoter methylation
      in AD transgenic mice. CONCLUSION: These results suggest a mechanism by which
      folic acid may prevent Abeta oligomer-induced neuronal toxicity.

PMID- 26224649
TI  - beta-catenin in epithelial tumorigenesis.

PMID- 26224651
TI  - HCC criteria for liver transplantation: Controversies.

PMID- 26224650
TI  - Lymphatic response to depilation-induced inflammation in mouse ear assessed with
      label-free optical lymphangiography.
AB  - BACKGROUND AND OBJECTIVES: Optical microangiography (OMAG) is a noninvasive
      technique capable of imaging 3D microvasculature. OMAG-based optical
      lymphangiography has been developed for 3D visualization of lymphatic vessels
      without the need for exogenous contrast agents. In this study, we utilize the
      optical lymphangiography to investigate dynamic changes in lymphatic response
      within skin tissue to depilation-induced inflammation by using mouse ear as a
      simple tissue model. MATERIALS AND METHODS: A spectral-domain optical coherence
      tomography (OCT) system is used in this study to acquire volumetric images of
      mouse ear. The system operates under the ultrahigh-sensitive OMAG scanning
      protocol with five repetitions for each B frame. An improved adaptive-threshold
      based method is proposed to segment lymphatic vessels from OCT microstructure
      images. Depilation is achieved by placing hair removal lotion on mouse ear pinna
      for 5 minutes. Three acquisitions are made before depilation, 3-minute and 30
      minute post-depilation, respectively. RESULTS: Right after the application of
      depilation lotion on the skin, we observe that the blind-ended sacs of initial
      lymphatics are mainly visible in a specific area of the normal tissue. At 5
      minutes, more collecting lymphatic vessels start to form, evidenced by their
      valve structure that only exists in collecting lymphatic vessels. The
      lymphangiogenesis is almost completed within 8 minutes in the inflammatory
      tissue. CONCLUSIONS: Our experimental results demonstrate that the OMAG-based
      optical lymphangiography has great potential to improve the understanding of
      lymphatic system in response to various physiological conditions, thus would
      benefit the development of effective therapeutics.

PMID- 26224652
TI  - Age effects on the nucleus of the lateral olfactory tract of the rat.
AB  - The olfactory deficits that occur during aging influence the quality of life and
      have been regarded as a risk factor for malnutrition in the elderly. The nucleus
      of the lateral olfactory tract (nLOT) is a cortical nucleus of the pallial
      amygdala that has been implicated in feeding behavior. Here we present
      quantitative data on the anatomy of the nLOT in the adult rat and on the effects
      of age on its structure and neurochemistry. Total neuron numbers, neuronal
      volumes, and volumes of layers 1-3 of the nLOT were estimated in adult and old
      male rats using stereological techniques. We also estimated the total number of
      interneurons expressing neuropeptide Y (NPY) and vasoactive intestinal
      polypeptide (VIP), and the numerical density of the nLOT cholinergic
      varicosities. Our data show that aging is associated with a reduction of the
      total neuron numbers in the nLOT, due to cell loss in layers 2 and 3. There were
      no age-related variations in neuronal volumes. Similarly, the volume of the nLOT
      was unchanged in aged rats, except in layer 3 where it was reduced. The numerical
      density of cholinergic varicosities was also unchanged in aged rats. Conversely,
      the total numbers of NPY- and VIP-immunoreactive neurons were reduced by 55% and
      30%, respectively, in aged rats. These findings include the nLOT in the list of
      cortical olfactory structures susceptible to aging and raise the possibility that
      the age-related changes that occur in the nLOT might contribute for the decline
      in olfactory functions reported in normal aging.

PMID- 26224653
TI  - Dunaliella tertiolecta (Chlorophyta) Avoids Cell Death Under Ultraviolet
      Radiation By Triggering Alternative Photoprotective Mechanisms.
AB  - The effect of different ultraviolet radiation (UVR) treatments combining PAR (P),
      UVA (A) and UVB (B) on the molecular physiology of Dunaliella tertiolecta was
      studied during 6 days to assess the response to chronic UVR exposure. UVR reduced
      cell growth but did not cause cell death, as shown by the absence of SYTOX Green
      labeling and cellular morphology. However, caspase-like enzymatic activities
      (CLs), (regarded as cell death proteases), were active even though the cells were
      not dying. Maximal quantum yield of fluorescence (Fv /Fm ) and photosynthetic
      electron transport rate (ETR) dropped. Decreased nonphotochemical quenching (NPQ)
      paralleled a drop in xanthophyll cycle de-epoxidation under UVB. Reactive oxygen
      species (ROS) and D1 protein accumulation were inversely correlated. PAB
      exhibited elevated ROS production at earlier times. Once ROS decayed, D1 protein
      recovered two-fold compared with P and PA at later stages. Therefore, PsbA gene
      was still transcribed, suggesting ROS involvement in D1 recovery by its direct
      effect on mRNA-translation. We add evidence of an UVB-induced positive effect on
      the cells when P is present, providing photoprotection and resilience, by means
      of D1 repair. This allowed cells to survive. The photoprotective mechanisms
      described here (which are counterintuitive in principle) conform to an important
      ecophysiological response regarding light stress acclimation. 

PMID- 26224654
TI  - A candidate packaging signal of human rotavirus differentiating Wa-like and DS-1
      like genomic constellations.
AB  - Rotavirus A (RVA) possesses a genome of 11 segmented RNAs. In human RVA, two
      major genomic constellations are represented by prototype strains Wa and DS-1.
      Here packaging signals differentiating Wa-like and DS-1-like genomic
      constellations were searched for by analyzing genomic sequences of Wa-like and DS
      1-like strains. One pair of 11 nucleotide sites in the coding regions of viral
      structural protein (VP) 2 and VP6 was found to be complementary specifically
      among Wa-like strains. These sites tended to be free from base-pairing in
      secondary structures of genomic segments, suggesting that they may serve as a
      packaging signal in Wa-like strains.

PMID- 26224655
TI  - Optimizing immobilization of avidin on surface-modified magnetic nanoparticles:
      characterization and application of protein-immobilized nanoparticles.
AB  - A simple optimization method of immobilization of avidin on magnetic
      nanoparticles (MNPs)' surface was proposed in this study. The avidin-immobilized
      MNPs were then developed and used to immobilize a model enzyme [Horseradish
      peroxidase (HRP)]. The loading capacity (LC) and activity of avidin-immobilized
      MNPs were optimized through selecting the most appropriate nanoparticle's size
      and shape, glutaraldehyde concentration, cross-linking reaction time, ultrasonic
      processing time, and initial concentration of avidin. The LC under optimized
      conditions was 63.37 +/- 1.29 mg avidin/g MNPs, and the immobilized protein was
      still able to maintain its high biological activity of 10.86 +/- 0.13 U/mg
      (biotin-binding activity of nature avidin was 14.1 U/mg) and better thermal
      stability compared to free avidin. A highly reusable, stable, and easily
      recovered immobilized HRP was obtained using MNPs as carriers. The immobilized
      HRP was reused repeatedly more than 9 times and retained more than 65 % of its
      original activity. 

PMID- 26224656
TI  - Fetal cerebral redistribution: a marker of compromise regardless of fetal size.

PMID- 26224657
TI  - Reentrainment Impairs Spatial Working Memory until Both Activity Onset and Offset
      Reentrain.
AB  - Compression of the active phase (alpha) during reentrainment to phase-shifted
      light-dark (LD) cycles is a common feature of circadian systems, but its
      functional consequences have not been investigated. This study tested whether
      alpha compression in Siberian hamsters (Phodopus sungorus) impaired their spatial
      working memory as assessed by spontaneous alternation (SA) behavior in a T-maze.
      Animals were exposed to a 1- or 3-h phase delay of the LD cycle (16 h light/8 h
      dark). SA behavior was tested at 4 multiday intervals after the phase shift, and
      alpha was quantified for those days. All animals failed at the SA task while
      alpha was decompressing but recovered spatial memory ability once alpha returned
      to baseline levels. A second experiment exposed hamsters to a 2-h light pulse
      either early or late at night to compress alpha without phase-shifting the LD
      cycle. SA behavior was impaired until alpha decompressed to baseline levels. In a
      third experiment, alpha was compressed by changing photoperiod (LD 16:8, 18:6,
      20:4) to see if absolute differences in alpha were related to spatial memory
      ability. Animals performed the SA task successfully in all 3 photoperiods. These
      data show that the dynamic process of alpha compression and decompression impairs
      spatial working memory and suggests that alpha modulation is a potential
      biomarker for assessing the impact of transmeridian flight or shift work on
      memory. 

PMID- 26224659
TI  - A method to tune the shape of protein-encapsulated polymeric microspheres.
AB  - Protein encapsulation technologies of polymeric microspheres currently in use
      have been optimized to effectively protect their "protein cargo" from
      inactivation occurring in biological environments, preserving its bioactivity
      during release up to several weeks. The scenario of protein delivery would
      greatly benefit by strategies enabling the production of non-spherical particles.
      Herein we report an easy and effective stamp-based method to produce poly-lactic
      glycolic-acid (PLGA) microparticles encapsulating Vascular Endothelial Growth
      Factor (VEGF) of different shapes. We demonstrate that PLGA microspheres can be
      deformed at room temperature exploiting solvent/non-solvent plasticization in
      order to preserve the properties of the starting microspheres. This gentle method
      allows the production of shaped particles that provide a prolonged release of
      VEGF in active form, as verified by an angiogenic assay. The retention of the
      biological activity of an extremely labile molecule, i.e. VEGF, lets us
      hypothesize that a wide variety of drug and protein encapsulated polymeric
      microspheres can be processed using this method. 

PMID- 26224660
TI  - Renal colic due to fatty tissue obstruction of the ureter following selective
      arterial embolisation of a 10 cm angiomyolipoma.
AB  - A 47-year-old man was admitted for preventive embolisation of a 10 cm
      angiomyolipoma (AML) of the right kidney. Three weeks after embolisation, he was
      readmitted at the emergency unit for a right renal colic. The CT scan confirmed
      the obstruction of the right ureter due to the presence of fatty tissue into the
      lumen. Understanding fatty tissue migration into the collecting system is not
      simple. We hypothesised that the use of alcohol during the embolisation procedure
      could have led to focal necrosis of the collecting system, thus enabling
      migration of fatty tissue into the renal calyces.

PMID- 26224658
TI  - Progress toward norovirus vaccines: considerations for further development and
      implementation in potential target populations.
AB  - Human norovirus infection causes significant medical and financial costs in the
      USA and abroad. Some populations, including young children, the elderly, and the
      immunocompromised, are at heightened risk of infection with this virus and
      subsequent complications, while others, such as healthcare workers and food
      handlers are at increased risk of transmitting it, and some are at risk of both.
      Human noroviruses are heterogeneous with new strains emerging periodically. In
      addition to viral diversity, incompletely understood characteristics, such as
      virus-host cell binding and duration of immunity after infection add to the
      challenges of creating a norovirus vaccine. Although much progress has been made
      in recent years, many questions remain to be answered. In this review, we discuss
      the important areas and relevant literature in considering human norovirus
      vaccine development and potential targets for implementation. 

PMID- 26224661
TI  - Human chemerin correlation in gingival crevicular fluid and tear fluid as markers
      of inflammation in chronic periodontitis and type-2 diabetes mellitus.
AB  - AIM: The aim of the present study was to evaluate the levels and correlation of
      human chemerin in gingival crevicular fluid (GCF) and tear fluid in chronic
      periodontitis (CP) subjects with and without type-2 diabetes mellitus (DM).
      MATERIALS AND METHODS: A total of 40 subjects were divided into three groups:
      group 1 had 10 periodontally healthy subjects; group 2 consisted of 15 CP
      subjects and group 3 had 15 type-2 DM subjects with CP. The GCF and tear fluid
      levels of human chemerin were quantified using enzyme linked immunosorbent assay
      (ELISA). Systemic parameters such as body mass index, glycated hemoglobin levels
      and fasting plasma glucose levels were evaluated. The clinical outcomes evaluated
      were gingival index (GI), probing depth (PD), and clinical attachment level
      (CAL), and the correlations of the two inflammatory mediators with clinical
      parameters were evaluated. RESULTS: Human chemerin levels increased from group 1
      to group 2 to group 3. The GCF and tear-fluid values of the inflammatory
      mediators correlated positively with each other and with the evaluated
      periodontal parameters (P < 0.05). CONCLUSION: Human chemerin can be considered
      as possible GCF and tear-fluid markers of inflammatory activity in CP and DM.

PMID- 26224662
TI  - A targeted functional RNA interference screen uncovers glypican 5 as an entry
      factor for hepatitis B and D viruses.
AB  - Chronic hepatitis B and D infections are major causes of liver disease and
      hepatocellular carcinoma worldwide. Efficient therapeutic approaches for cure are
      absent. Sharing the same envelope proteins, hepatitis B virus and hepatitis delta
      virus use the sodium/taurocholate cotransporting polypeptide (a bile acid
      transporter) as a receptor to enter hepatocytes. However, the detailed mechanisms
      of the viral entry process are still poorly understood. Here, we established a
      high-throughput infectious cell culture model enabling functional genomics of
      hepatitis delta virus entry and infection. Using a targeted RNA interference
      entry screen, we identified glypican 5 as a common host cell entry factor for
      hepatitis B and delta viruses. CONCLUSION: These findings advance our
      understanding of virus cell entry and open new avenues for curative therapies. As
      glypicans have been shown to play a role in the control of cell division and
      growth regulation, virus-glypican 5 interactions may also play a role in the
      pathogenesis of virus-induced liver disease and cancer.

PMID- 26224663
TI  - Impact of the serum ferritin concentration in liver transplantation.
AB  - The serum ferritin (SF) concentration is a widely available and objective
      laboratory parameter. SF is also widely recognized as an acute-phase reactant.
      The purpose of the present study was to identify the chronological changes in the
      recipient's SF concentration during liver transplantation (LT) and to clarify
      factors having an effect on the recipient's intraoperative SF level. In addition,
      the study retrospectively evaluated the usefulness of measuring SF during LT.
      Ninety-eight pediatric recipients were retrospectively analyzed. The data were
      analyzed and compared according to the SF level in the recipient. Patients were
      classified into 2 groups based on the intraoperative peak SF levels of <= 1000
      ng/mL (low-SF group) or >1000 ng/mL (high-SF group). The SF value increased
      dramatically after reperfusion and fell to normal levels within the early
      postoperative period. The warm ischemia time (WIT) was significantly longer in
      the high-SF group (47.0 versus 58.5 minutes; P = 0.003). In addition, a
      significant positive correlation was observed between the peak SF value and WIT
      (r = 0.35; P < 0.001). There were significant positive correlations between the
      peak SF value and the donors' preoperative laboratory data, including
      transaminases, cholinesterase, hemoglobin, transferrin saturation, and SF, of
      which SF showed the strongest positive correlation (r = 0.74; P < 0.001). The
      multivariate analysis revealed that WIT and donor's SF level were a significant
      risk factor for high SF level in the recipient (P = 0.007 and 0.02,
      respectively). In conclusion, the SF measurement can suggest the degree of
      ischemia/reperfusion injury (IRI). A high SF level in the donor is associated
      with the risk of further acute reactions, such as IRI, in the recipient.

PMID- 26224664
TI  - The canonical DHHC motif is not absolutely required for the activity of the yeast
      S-acyltransferases Swf1 and Pfa4.
AB  - Protein S-acyltransferases, also known as palmitoyltransferases (PATs), are
      characterized by the presence of a 50-amino acid domain called the DHHC domain.
      Within this domain, these four amino acids constitute a highly conserved motif.
      It has been proposed that the palmitoylation reaction occurs through a palmitoyl
      PAT covalent intermediate that involves the conserved cysteine in the DHHC motif.
      Mutation of this cysteine results in lack of function for several PATs, and DHHA
      or DHHS mutants are used regularly as catalytically inactive controls. In a
      genetic screen to isolate loss-of-function mutations in the yeast PAT Swf1, we
      isolated an allele encoding a Swf1 DHHR mutant. Overexpression of this mutant is
      able to partially complement a swf1Delta strain and to acylate the Swf1
      substrates Tlg1, Syn8, and Snc1. Overexpression of the palmitoyltransferase Pfa4
      DHHA or DHHR mutants also results in palmitoylation of its substrate Chs3. We
      also investigated the role of the first histidine of the DHHC motif. A Swf1 DQHC
      mutant is also partially active but a DQHR is not. Finally, we show that Swf1
      substrates are differentially modified by both DHHR and DQHC Swf1 mutants. We
      propose that, in the absence of the canonical mechanism, alternative suboptimal
      mechanisms take place that are more dependent on the reactivity of the acceptor
      protein. These results also imply that caution must be exercised when proposing
      non-canonical roles for PATs on the basis of considering DHHC mutants as
      catalytically inactive and, more generally, contribute to an understanding of the
      mechanism of protein palmitoylation. 

PMID- 26224665
TI  - Enhanced Photocatalytic Reduction of CO2 to CO through TiO2 Passivation of InP in
      Ionic Liquids.
AB  - A robust and reliable method for improving the photocatalytic performance of InP,
      which is one of the best known materials for solar photoconversion (i.e., solar
      cells). In this article, we report substantial improvements (up to 18*) in the
      photocatalytic yields for CO2 reduction to CO through the surface passivation of
      InP with TiO2 deposited by atomic layer deposition (ALD). Here, the main
      mechanisms of enhancement are the introduction of catalytically active sites and
      the formation of a pn-junction. Photoelectrochemical reactions were carried out
      in a nonaqueous solution consisting of ionic liquid, 1-ethyl-3-methylimidazolium
      tetrafluoroborate ([EMIM]BF4), dissolved in acetonitrile, which enables CO2
      reduction with a Faradaic efficiency of 99% at an underpotential of +0.78 V.
      While the photocatalytic yield increases with the addition of the TiO2 layer, a
      corresponding drop in the photoluminescence intensity indicates the presence of
      catalytically active sites, which cause an increase in the electron-hole pair
      recombination rate. NMR spectra show that the [EMIM](+) ions in solution form an
      intermediate complex with CO2(-), thus lowering the energy barrier of this
      reaction.

PMID- 26224666
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Integrated treatments
      for osteoporosis toward harmony of bone and muscle].
AB  - Osteoporosis and sarcopenia directly affect healthy life expectancy in elderly
      people ; therefore, both diseases become social problem around the world.
      Sarcopenia increases the risk of osteoporotic fracture. Thus, not only agents
      affecting bone tissue directly but also treatments for sarcopenia are important
      for management of osteoporosis. Recently, it has been shown that there is an
      interaction between bone and muscle. Several hormones affect muscle and bone
      simultaneously. Moreover, myokines secreted from muscle are reported to regulate
      bone metabolism. On the other hand, several systemic and local factors derived
      from bone also affect muscle tissue. Therefore, further studies are necessary to
      develop the integrated treatments for osteoporosis toward harmony of bone and
      muscle. 

PMID- 26224667
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Regulation of
      chondrogenesis and cartilage regeneration by molecular and developmental
      biology].
AB  - In decades, the signaling pathways that regulate chondrogenesis and the
      differentiation of chondrocytes have been identified. Molecular biological
      understanding of the commitment of mesenchymal cells to the chondrogenic lineage,
      which leads to endochondral bone formation, is necessary to understand
      pathophysiology of bone/cartilage metabolic diseases and cartilage degenerative
      diseases. In this review, we show how multiple growth factors and signaling
      molecules are integrated to activate a series of transcription factors in
      connection with morphological cell features, which regulates chondrogenesis and
      chondrocyte differentiation. 

PMID- 26224668
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Genomic medicine of bone
      and joint diseases : present and future].
AB  - Susceptibility genes for various kinds of common diseases have been identified by
      the genome-wide association study (GWAS) and the outcome is changing the clinical
      medicine significantly. Musculoskeletal disease is no exception. In this paper, I
      review the current status and prospect of GWAS in musculoskeletal diseases in
      Japan by focusing on representative common musculoskeletal diseases : disc
      herniation, adolescent idiopathic scoliosis and ossification of the posterior
      longitudinal ligament of the spine. 

PMID- 26224669
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Bone metabolism and
      intercellular network].
AB  - Bone is an active organ under continuous bone remodeling that consists of bone
      resorption and synthesis. The process requires precise communication among bone
      cells including osteoclasts, osteoblasts and osteocytes. However, the detailed
      mechanisms of bone cell interactions have been poorly understood. Technological
      advances and the accumulating evidence in recent years enabled a better
      understanding of the communication and coupling mechanisms at the cellular and
      molecular levels. These studies provide new insights into bone disease
      pathogenesis and molecular basis for novel therapeutic approaches. 

PMID- 26224670
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Gene regulatory network
      in development and maintenance of skeletal muscle cells].
AB  - In this section, we describe about key upstream factors to lead to the
      activation, differentiation of skeletal muscle cells in the mouse and chick
      models, such as Pax3/Pax7 genes. They are involved in gene regulatory networks at
      various sites of skeletal muscle formation. And microRNAs intervene with emerging
      evidences for novel roles to regulate key factors in myogenesis. We discuss new
      myogenic insights into mechanisms underlying the transcriptional activity of
      these factors. 

PMID- 26224671
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Sex hormone receptors
      dependent gene expression mechanisms in locomotive tissues].
AB  - There are large sex differences in the prevalence of locomotive diseases such as
      osteoporosis and osteoarthritis. Given that the onset of diseases is the failure
      of homeostasis, there might be a sex difference in the maintenance of homeostasis
      of locomotive organs/tissues. The factors of sex differences consist of sex
      chromosomes and sex hormones. Because the majority of locomotive diseases were
      occurred in the elderly people, the deficiency of sex hormones might play a role
      in pathogenesis of locomotive diseases. Sex hormones exert their functions by
      binding with their own specific nuclear receptors, which regulate transcription
      of the target genes in the target tissues. In this chapter, the transcriptional
      regulation by sex hormone receptors in bone and muscle will be discussed based on
      the reports about the mice lacking sex hormone receptor (s). 

PMID- 26224672
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. The role of
      extracellular matrix and its pathogenesis in musculoskeletal disorders].
AB  - Extracellular matrix is present in all organs, but its strength and character
      differ greatly from structure to structure. Organs in the musculoskeletal system
      require tissue specific strength, resistance to strains and elasticity.
      Extracellular matrix that forms the scaffold in tissues, is able to detect
      mechanical stress, and undergoes remodeling to dissipate the strain. Here we
      explain how excess mechanical and biochemical stresses disrupt normal matrix
      remodeling resulting in reduced strength/elasticity. 

PMID- 26224673
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Use of iPS cells in
      regenerative therapy and drug discovery for cartilage diseases].
AB  - Induced pluripotent stem (iPS) cells can be generated by transiently expressing
      defined factors in somatic cells such as dermal fibroblasts and blood cells and
      culturing them in specific medium. iPS cells are expected to provide new tools
      for research and development of therapies for various diseases because of two
      important properties : 1) they can be differentiated into any type of somatic
      cell (pluripotency) and 2) they can be expanded infinitely (self renew). Research
      for the transplantation of iPS cell-derived cartilage/chondrocytes and drug
      discovery by iPS cell-based disease modeling are ongoing. 

PMID- 26224674
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. The research for
      musculoskeletal disease using genome editing technology].
AB  - Genome editing is a genetic technology by which any DNA sequence is inserted,
      replaced or deleted. Genome editing has been making rapid progress recently, with
      the development of new techniques such as ZFN, TALEN and CRISPR/Cas9. Genome
      editing can be applied to various fields ranging from the production of knock out
      animals to gene therapy. This section summarizes these new genome editing
      technologies and its applications. 

PMID- 26224675
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Musculoskeletal disease
      research by using imaging technique].
AB  - Intravital fluorescence imaging technique is a method that enables to visualize
      behavior and function of molecules and cells in vivo . Recently, the intravital
      fluorescence imaging technique has developed rapidly. In particular, development
      of functional fluorescent proteins and fluorescent dyes in conjunction with
      appropriate equipment including two-photon fluorescence microscope and image
      processing software enables to investigate bone and cartilage tissues in vivo .
      Here we show recent technological development of the intravital fluorescence
      imaging in biology. Moreover, we would discuss about issues of the intravital
      fluorescence imaging and the application of the fluorescent imaging approaches to
      bone and cartilage biology. 

PMID- 26224676
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Pathology and therapy
      for skeletal disorder].
AB  - There are a lot of skeletal disorders, and the pathogenesis underlying those
      diseases is varied. However, mechanisms underlying some disorders, particularly
      osteoporosis and rheumatoid arthritis, were, at least in part, clarified and
      therapeutic targets for those diseases were identified. Hypoxia inducible factor
      1 alpha was identified to be required for osteoclast activation in postmenopausal
      osteoporosis, while signal transducer and activator of transcription 3 was
      demonstrated to contribute for development of chronic arthritis and joint
      destruction in rheumatoid arthritis. 

PMID- 26224677
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Pathophysiology of
      articular cartilage and its new therapeutic targets].
AB  - Osteoarthritis (OA) is a group of heterogenetic disorders occurring due to a
      variety of causes, resulting in cartilage degeneration and finally in cartilage
      loss. No conservative drug therapy with high-quality evidence in terms of OA
      treatment has been developed as of yet. In recent years, the relation between OA
      and lifestyle related diseases along with the involvement of joint tissues other
      than the cartilage is becoming clarified through many epidemiological studies and
      basic researches. These topics are introduced in order to put new OA therapeutic
      targets into perspective. Moreover, problems in the evaluation for intraarticular
      injection of hyaluronic acid, which is a drug therapy used in medical practice
      for long term, are investigated and a discussion is carried out on the evaluation
      method of future drug therapies for OA. 

PMID- 26224678
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Recent progress in
      molecular pathogensis and treatment for muscle disorders].
AB  - There are a variety of different skeletal muscle diseases, each of which carries
      its own unique set of symptoms. One of the most common characteristics affecting
      the skeletal muscles is muscular atrophy. Indeed, muscle atrophy occurs under a
      variety of pathologyical conditions, including sarcopenia, glucocortcoid
      treatment. Recently, its underlying molecular has been intensively studied and
      novel therapy is being developed. 

PMID- 26224679
TI  - [Analysis of Musculoskeletal Systems and Their Diseases. Pathology and treatment
      for injuries of the tendon and ligament].
AB  - Tendons and ligaments are dense connective fibers mainly composed of type I
      collagen. However, the structure, function, and cellular behavior are different
      between tendons and ligaments. Anatomic, biological, and developmental studies
      have revealed the distinct differentiation process of tendons, ligaments, and
      these attachments to the bones (so-called entheses). In addition, arthroscopic
      devices, surgical materials, and operative techniques for the treatment of
      tendon/ligament injuries have been dramatically improved. Based on these
      backgrounds, the treatment strategies of tendon/ligament disorders have changed
      in recent years. This review focused on the pathology of tendon and ligament
      injuries involved in the tear of the rotator cuff and anterior cruciate ligament.
      We also described the current treatment for the tendon/ligament injuries and the
      future regeneration therapy against these connective tissue injuries. 

PMID- 26224680
TI  - [Bone and Calcium Metabolisms Associated with Dental and Oral-Maxillofacial
      Diseases. Bone remodeling and alveolar bone homeostasis].
AB  - Bone, which support motile organ and periodontal tissue, is renewing throughout
      our life. This restructuring process is called "bone remodeling" , and
      osteoclasts and osteoblasts play a crucial role in this process. Bone remodeling
      is important not only for normal bone mass and strength, but also for mineral
      homeostasis. Bone remodeling is stringently regulated by communication between
      bone component cells such as osteoclasts, osteoblasts and osteocytes. An
      imbalance of this process is often linked to various bone diseases. Alveolar bone
      remodeling is directly influenced by occlusal force from the teeth. Thus, the
      elucidation of the regulatory mechanisms involved in alveolar bone remodeling is
      critical for a deeper understanding of the maintenance of healthy tooth and
      dental disease. 

PMID- 26224681
TI  - PI3K Inhibitor Combined With Chemotherapy Can Enhance the Apoptosis of
      Neuroblastoma Cells In Vitro and In Vivo.
AB  - Activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is a
      novel poor prognostic indicator of neuroblastoma (NB), and the positive effects
      of chemotherapy on NB have been confirmed. In this study, we investigated the
      effect of small molecule PI3K inhibitor PI103 on chemosensitivity. The PI3K
      inhibitor cooperates with doxorubicin to synergistically induce apoptosis and to
      reduce tumor growth of NB in in vitro and in vivo models. Human NB cells, SH-SY5Y
      and SK-N-BE(2), were treated with PI103 combined doxorubicin-enhanced Bid
      cleavage, activated Bax, and caspase 3. Activation of caspase 3 was also observed
      in xenografts of NB in nude mice upon combination of doxorubicin with the
      specific PI3K inhibitor PI103. Cell viability was assessed with 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Both PI103 and
      doxorubicin inhibited growth of NB in vitro and PI103 induced a G1 arrest of NB
      cells. PI103 combined doxorubicin significantly inhibits the growth of
      established NB tumors, induced apoptosis of tumor cells, and improved the
      survival of mice in vivo Taken together, our findings suggest that PI3K
      inhibition seems to be a promising option to sensitize tumor cells for
      chemotherapy in NB, which may be effective in the treatment of NBs.

PMID- 26224682
TI  - Development of an MgO-based binder for stabilizing fine sediments and storing
      CO2.
AB  - An MgO-based binder was developed that could stabilize fine dredged sediments for
      reuse and store CO2. Initially, a binder consisting of fly ash (FA) and blast
      furnace slag (BFS) was developed by using alkaline activators such as KOH, NaOH,
      and lime. The FA0.4-BFS0.6 binder (mixed at a FA-to-BFS weight ratio of 4:6)
      showed the highest compressive strength of 10.7 MPa among FA/BFS binders when 5 M
      KOH was used. When lime (L) was tested as an alkaline activator, the strength was
      comparable with those obtained when KOH or NaOH was used. The L0.1
      (FA0.4BFS0.6)0.9 binder (10 % lime mixed with the FA/BFS binder) showed the
      highest strength of 11.0 MPa. Finally, by amending this L0.1-(FA0.4BFS0.6)0.9
      binder with MgO, a novel MgO-based binder (MgO0.5-(L0.1-(FA0.4BFS0.6)0.9) 0.5)
      was developed, which demonstrated the 28th day strength of 11.9 MPa. The MgO
      based binder was successfully applied to stabilize a fine sediment to yield a
      compressive strength of 4.78 MPa in 365 days, which was higher than that obtained
      by the Portland cement (PC) system (3.22 MPa). Carbon dioxide sequestration was
      evidenced by three observations: (1) the decrease in pH of the treated sediment
      from 12.2 to 11.0; (2) the progress of the carbonation front inward the treated
      sediment; and (3) the presence of magnesium carbonates. The thermogravimetric
      analysis (TGA) results showed that 67.2 kg of CO2 per ton of the treated sediment
      could be stored under the atmospheric condition during 1 year.

PMID- 26224683
TI  - Environmental modeling of uranium interstitial compositions of non-stoichiometric
      oxides: experimental and theoretical analysis.
AB  - Study of uranium interstitial compositions of non-stoichiometric oxides UO2+x (x
      ? 0.1-0.02) in gas and condense phases has been presented, using various soft
      ionization mass spectrometric methods such as ESI-, APCI-, and MALDI-MS at a wide
      dynamic temperature gradient (? 25-300  degrees C). Linearly polarized
      vibrational spectroscopy has been utilized in order to assign unambiguously, the
      vibrational frequencies of uranium non-stoichiometric oxides. Experimental design
      has involved xUO2.66.yUO2.33, xUO2.66.yUO2.33/SiO2, xUO2.66.yUO2.33/SiO2 (NaOH)
      and SiO2/x'NaOH.y'UO2(NO3)2.6H2O, multicomponent systems (x = 1, y ? 0.1-1.0 and
      x' = 1, y' ? 0.1-0.6) as well as phase transitions UO2(NO3)2.6H2O ->
      {U4O9(UO2.25)} -> U3O7(UO2.33) -> U3O8(UO2.66) -> {UO3}, thus ensuring a maximal
      representativeness to real environmental conditions, where diverse chemical,
      geochemical and biochemical reactions, including complexation and sorption onto
      minerals have occurred. Experimental factors such as UV-irradiation, pH,
      temperature, concentration levels, solvent types and ion strength have been taken
      into consideration, too. As far as uranium speciation represents a challenging
      analytical task in terms of chemical identification diverse coordination species,
      mechanistic aspects relating incorporation of oxygen into UO 2+x form the shown
      full methods validation significantly impacts the field of environmental
      radioanalytical chemistry. UO2 is the most commonly used fuel in nuclear reactors
      around the globe; however, a large non-stoichiometric range ? UO1.65-UO2.25 has
      occurred due to radiolysis of water on UO2 surface yielding to H2O2, OH(.), and
      more. Each of those compositions has different oxygen diffusion. And in this
      respect enormous effort has been concentrated to study the potential impact of
      hazardous radionuclide on the environment, encompassing from the reprocessing to
      the disposal stages of the fuel waste, including the waste itself, the processes
      in the waste containers, the clay around the containers, and geological
      processes. In a broader sense, thereby, this study contributes to field of
      environmental analysis highlighting the great ability of various soft-ionization
      MS methods, particularly, MALDI-MS one, for direct assay of complex
      multicomponent heterogeneous mixtures at fmol-attomol concentration ranges, along
      with it the great instrumental features allowing, not only meaningful
      quantitative, but also structural information of the analytes, thus making the
      method indispensable for environmental speciation of radionuclides, generally.

PMID- 26224684
TI  - Imaging lexicon for acute pancreatitis: 2012 Atlanta Classification revisited.
AB  - The original 1992 Atlanta Classification System for acute pancreatitis was
      revised in 2012 by the Atlanta Working Group, assisted by various national and
      international societies, through web-based consensus. This revised classification
      identifies two phases of acute pancreatitis: early and late. Acute pancreatitis
      can be either oedematous interstitial pancreatitis or necrotizing pancreatitis.
      Severity of the disease is categorized into three levels: mild, moderately severe
      and severe, depending upon organ failure and local/systemic complications.
      According to the type of pancreatitis, collections are further divided into acute
      peripancreatic fluid collection, pseudocyst, acute necrotic collection, and
      walled-off necrosis. Insight into the revised terminology is essential for
      accurate communication of imaging findings. In this review article, we will
      summarize the updated nomenclature and illustrate corresponding imaging findings
      using examples. 

PMID- 26224685
TI  - Pancreatitis of ectopic pancreatic tissue: a rare cause of gastric outlet
      obstruction.
AB  - Inflammation in ectopic pancreatic tissue can clinically present with pain or
      obstructive symptoms, depending on the location of the ectopic tissue. We present
      a rare case of gastric outlet obstruction secondary to pancreatitis of ectopic
      pancreatic tissue in the pylorus.

PMID- 26224686
TI  - Social stress in mice induces urinary bladder overactivity and increases TRPV1
      channel-dependent afferent nerve activity.
AB  - Social stress has been implicated as a cause of urinary bladder hypertrophy and
      dysfunction in humans. Using a murine model of social stress, we and others have
      shown that social stress leads to bladder overactivity. Here, we show that social
      stress leads to bladder overactivity, increased bladder compliance, and increased
      afferent nerve activity. In the social stress paradigm, 6-wk-old male C57BL/6
      mice were exposed for a total of 2 wk, via barrier cage, to a C57BL/6 retired
      breeder aggressor mouse. We performed conscious cystometry with and without
      intravesical infusion of the TRPV1 inhibitor capsazepine, and measured pressure
      volume relationships and afferent nerve activity during bladder filling using an
      ex vivo bladder model. Stress leads to a decrease in intermicturition interval
      and void volume in vivo, which was restored by capsazepine. Ex vivo studies
      demonstrated that at low pressures, bladder compliance and afferent activity were
      elevated in stressed bladders compared with unstressed bladders. Capsazepine did
      not significantly change afferent activity in unstressed mice, but significantly
      decreased afferent activity at all pressures in stressed bladders.
      Immunohistochemistry revealed that TRPV1 colocalizes with CGRP to stain nerve
      fibers in unstressed bladders. Colocalization significantly increased along the
      same nerve fibers in the stressed bladders. Our results support the concept that
      social stress induces TRPV1-dependent afferent nerve activity, ultimately leading
      to the development of overactive bladder symptoms. 

PMID- 26224687
TI  - Two inwardly rectifying potassium channels, Irk1 and Irk2, play redundant roles
      in Drosophila renal tubule function.
AB  - Inwardly rectifying potassium channels play essential roles in renal physiology
      across phyla. Barium-sensitive K(+) conductances are found on the basolateral
      membrane of a variety of insect Malpighian (renal) tubules, including Drosophila
      melanogaster. We found that barium decreases the lumen-positive transepithelial
      potential difference in isolated perfused Drosophila tubules and decreases fluid
      secretion and transepithelial K(+) flux. In those insect species in which it has
      been studied, transcripts from multiple genes encoding inwardly rectifying K(+)
      channels are expressed in the renal (Malpighian) tubule. In Drosophila
      melanogaster, this includes transcripts of the Irk1, Irk2, and Irk3 genes. The
      role of each of these gene products in renal tubule function is unknown. We found
      that simultaneous knockdown of Irk1 and Irk2 in the principal cell of the fly
      tubule decreases transepithelial K(+) flux, with no additive effect of Irk3
      knockdown, and decreases barium sensitivity of transepithelial K(+) flux by ~50%.
      Knockdown of any of the three inwardly rectifying K(+) channels individually has
      no effect, nor does knocking down Irk3 simultaneously with Irk1 or Irk2.
      Irk1/Irk2 principal cell double-knockdown tubules remain sensitive to the
      kaliuretic effect of cAMP. Inhibition of the Na(+)/K(+)-ATPase with ouabain and
      Irk1/Irk2 double knockdown have additive effects on K(+) flux, and 75% of
      transepithelial K(+) transport is due to Irk1/Irk2 or ouabain-sensitive pathways.
      In conclusion, Irk1 and Irk2 play redundant roles in transepithelial ion
      transport in the Drosophila melanogaster renal tubule and are additive to
      Na(+)/K(+)-ATPase-dependent pathways. 

PMID- 26224688
TI  - Limited capacity for glucose oxidation in fetal sheep with intrauterine growth
      restriction.
AB  - Intrauterine growth-restricted (IUGR) fetal sheep, produced by placental
      insufficiency, have lower oxygen concentrations, higher lactate concentrations,
      and increased hepatic glucose production that is resistant to suppression by
      insulin. We hypothesized that increased lactate production in the IUGR fetus
      results from reduced glucose oxidation, during basal and maximal insulin
      stimulated conditions, and is used to support glucose production. To test this,
      studies were performed in late-gestation control (CON) and IUGR fetal sheep under
      basal and hyperinsulinemic-clamp conditions. The basal glucose oxidation rate was
      similar and increased by 30-40% during insulin clamp in CON and IUGR fetuses (P <
      0.005). However, the fraction of glucose oxidized was 15% lower in IUGR fetuses
      during basal and insulin-clamp periods (P = 0.05). IUGR fetuses also had four
      fold higher lactate concentrations (P < 0.001) and lower lactate uptake rates (P
      < 0.05). In IUGR fetal muscle and liver, mRNA expression of pyruvate
      dehydrogenase kinase (PDK4), an inhibitor of glucose oxidation, was increased
      over fourfold. In IUGR fetal liver, but not skeletal muscle, mRNA expression of
      lactate dehydrogenase A (LDHA) was increased nearly fivefold. Hepatic expression
      of the gluconeogenic genes, phosphoenolpyruvate carboxykinase (PCK)1, and PCK2,
      was correlated with expression of PDK4 and LDHA. Collectively, these in vivo and
      tissue data support limited capacity for glucose oxidation in the IUGR fetus via
      increased PDK4 in skeletal muscle and liver. We speculate that lactate production
      also is increased, which may supply carbon for glucose production in the IUGR
      fetal liver. 

PMID- 26224689
TI  - The effect of resting blood flow occlusion on exercise tolerance and W'.
AB  - It has previously been postulated that the anaerobic work capacity (W') may be
      utilized during resting blood flow occlusion in the absence of mechanical work.
      We tested the hypothesis that W' would not be utilized during an initial range of
      time following the onset of resting blood flow occlusion, after which W' would be
      utilized progressively more. Seven men completed blood flow occlusion constant
      power severe intensity handgrip exercise to task failure following 0, 300, 600,
      900, and 1,200 s of resting blood flow occlusion. The work performed above
      critical power (CP) was not significantly different between the 0-, 300-, and 600
      s conditions and was not significantly different from the total W' available.
      Significantly less work was performed above CP during the 1,200-s condition than
      the 900-s condition (P < 0.05), while both conditions were significantly less
      than the 0-, 300-, and 600-s conditions (P < 0.05). The work performed above CP
      during these conditions was significantly less than the total W' available (P <
      0.05). The utilization of W' during resting blood flow occlusion did not begin
      until 751 +/- 118 s, after which time W' was progressively utilized. The current
      findings demonstrate that W' is not utilized during the initial ~751 s of resting
      blood flow occlusion, but is progressively utilized thereafter, despite no
      mechanical work being performed. Thus, the utilization of W' is not exclusive to
      exercise, and a constant amount of work that can be performed above CP is not the
      determining mechanism of W'. 

PMID- 26224690
TI  - Economic Burden of HIV Antiretroviral Therapy Adverse Events in the United
      States.
AB  - OBJECTIVE: To estimate health care costs associated with medical events
      identified as antiretroviral therapy (ART)-attributable adverse events (AEs).
      METHODS: During September 2006 to June 2012, adults with >=1 HIV International
      Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code
      (042/V08), >=1 claim for ART prescription (March 2007-June 2011; index date), and
      continuous health plan enrollment for >=6 months pre- and >=12 months postindex
      were included (IMS' PharMetrics Plus Health Plan Claims Database). Patients with
      events of interest/ART claim during preindex period or with pregnancy/hepatitis C
      virus diagnosis/hepatitis B virus/cancer/tuberculosis during the study period
      were excluded. Postindex medical events were defined as first diagnosis code of
      event with ART claim <=60 days prior to start of the event. RESULTS: Differences
      in median total all-cause health care costs observed for diabetes/insulin
      resistance management (US$14,547 median all-cause health care costs during time
      periods identified as diabetes/insulin resistance medical events versus US$11,237
      without diabetes/insulin resistance events; P=.0021), lipid disorders (US$12,825
      versus US$10,033; P=.0004), and renal disorders (US$1389 versus US$0; P<.0001).
      DISCUSSION/CONCLUSION: Health care costs of ART AEs should be key consideration
      for payers/providers in HIV management.

PMID- 26224691
TI  - Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation
      of Vaccine Efficacy.
AB  - The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus
      macaques (CMs) to establish the relationship among vaccine doses, antibody
      titers, and survival following an aerosol challenge with a lethal dose of
      Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V
      doses on a three-dose schedule (days 0, 56, and 121) to provide a range of
      survival outcomes. The humoral immune response following vaccination was
      evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked
      immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on
      day 149. Vaccine doses and antibody responses were each significantly associated
      with the probability of CM survival (P < 0.0001). Vaccination also decreased
      signs of pneumonic plague in a dose-dependent manner. There were statistically
      significant correlations between the vaccine dose and the time to onset of fever
      (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to
      onset of elevated respiratory rate (P = 0.0003), and the time to onset of
      decreased activity (P = 0.0251) postinfection in animals exhibiting these
      clinical signs. Delays in the onset of these clinical signs of disease were
      associated with larger doses of rF1V. Immunization with >= 12 MUg of rF1V
      resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody
      titers correlate with survival, rF1V bridge ELISA titers can be used as a
      correlate of protection.

PMID- 26224693
TI  - [Pain and old age].

PMID- 26224692
TI  - The effect of antibiotics on the microbiome in acute exacerbations of chronic
      rhinosinusitis.
AB  - BACKGROUND: Current treatment of acute exacerbations of chronic rhinosinusitis
      (CRS) is driven by identification of predominant bacteria using culture-based
      methods and determination of antibiotic sensitivities. The objective of this
      study was to evaluate the response of the sinonasal microbiome to antibiotic
      therapy in the setting of an acute exacerbation of CRS. METHODS: Aspirate and
      swab samples for culture and DNA analysis were collected bilaterally from 8 CRS
      patients presenting with acute exacerbations. Patients were started on a 2-week
      course of a culture-directed antibiotic after sensitivities were determined.
      Repeat samples were taken immediately on the completion of treatment. DNA was
      extracted from each sample, amplified using bacterial 16S primers and sequenced.
      Bacterial abundance was determined by quantitative polymerase chain reaction
      (qPCR). Diversity metrics of the microbiota between pretreatment and
      posttreatment samples were calculated. RESULTS: There was significantly more
      bacterial DNA present in the pretreatment group than in the posttreatment group.
      An increase in alpha-diversity was found in the posttreatment group relative to
      the pretreatment group (p < 0.05 in each comparison) with swab sampling, but not
      by aspirate sampling. The predominant organism identified by 16S sequencing
      correlated with the culture-identified bacteria genus in each patient.
      CONCLUSION: Significant differences exist in the diversity of bacteria
      populations during acute exacerbations of CRS and after antimicrobial treatment.
      After therapy, the increase in diversity is accompanied by a decrease in the
      total of abundance of the bacterial population.

PMID- 26224694
TI  - Systematic review of the economic evidence on home visitation programmes for
      vulnerable pregnant women.
AB  - INTRODUCTION: A systematic review of the economic evidence on home visitation
      programmes for young or vulnerable pregnant women was undertaken to provide a
      summary of the existing literature of these interventions. SOURCES OF DATA:
      Relevant studies were identified from a number of sources including large
      databases, free text search on Google Scholar as well as hand-searching of the
      obtained references. The search yielded a large number of papers, of which 12
      were considered appropriate to be included in the review. These were either full
      or partial economic evaluations: four studies were cost-benefit analyses, three
      were cost-effectiveness analyses and the remaining were costing studies. AREAS OF
      AGREEMENT: The review highlighted the paucity of good quality economic
      evaluations in the area of home visiting programmes for young or vulnerable
      pregnant women. Methods varied substantially between the studies spanning from
      differing data sources (e.g. single randomized trials or meta-analyses) to
      different perspectives taken, cost items and outcomes included in the analysis.
      AREAS OF CONTROVERSY: It is difficult to establish a coherent body of economic
      evidence for these interventions and draw a firm conclusion on their value for
      money. GROWING POINTS: Home visiting programmes are complex interventions, with
      impact on the lives of mothers and their children. The funding of such
      interventions should be based on rigorous effectiveness and economic evidence.
      AREAS TIMELY FOR DEVELOPING RESEARCH: There is a need for well-designed economic
      evaluations which will follow the appropriate methodological guidelines and also
      take into account the complexity of such interventions. These analyses should
      preferably consider multiple perspectives and allow for the fact that the
      majority of the benefits accrue in the long-term future.

PMID- 26224695
TI  - Commissioning for equity in the NHS: rhetoric and practice.
AB  - BACKGROUND: This paper reviews evidence on equity as a policy goal of resource
      allocation in the English NHS, focussing on the role of clinical commissioning
      groups (CCGs) as purchasers of health services since 2013 and their capacity to
      achieve equity through the process of commissioning. SOURCES OF DATA: A
      systematic search of literature published since 1990 and review of grey
      literature, including policy documents published by CCGs and other organizations
      in the healthcare system. AREAS OF AGREEMENT: Despite a stated policy commitment
      to equity of access in the NHS, the 2012 reforms have created a structure that
      allows and encourages great variation between devolved purchasers of care. AREAS
      OF CONTROVERSY: Evidence suggests that CCGs, which are structurally separated
      from public health, have limited capacity and incentives to commission for
      equity. Concepts of equity of access and health inequalities lack consistent
      definitions and may not be implemented. However, it remains unclear whether
      variation between CCGs implies inequity. GROWING POINTS: The 2012 reforms have
      sought to contain costs and improve quality, thus achieving efficiency gains,
      while equity has remained an afterthought. The NHS should be expected to work
      towards equity of access to healthcare and can contribute to reducing health
      inequalities; however to achieve a more equitable distribution of health, wider
      social policies are also needed. AREAS TIMELY FOR DEVELOPING RESEARCH: Additional
      assessments of structural capacity should be complemented by further development
      of indicators of equity of access and studies that quantify inequities. Research
      should also explore how an equity principle can be embedded in commissioning,
      which currently revolves around cost containment and efficiency.

PMID- 26224696
TI  - Police Mental Health Partnership project: Police Ambulance Crisis Emergency
      Response (PACER) model development.
AB  - OBJECTIVES: To review internationally recognized models of police interactions
      with people experiencing mental health crises that are sometimes complex and
      associated with adverse experience for the person in crisis, their family and
      emergency service personnel. To develop, implement and review a partnership model
      trial between mental health and emergency services that offers alternative
      response pathways with improved outcomes in care. METHODS: Three unique models of
      police and mental health partnership in the USA were reviewed and used to develop
      the PACER (Police Ambulance Crisis Emergency Response) model. A three month trial
      of the model was implemented and evaluated. RESULTS: Significant improvements in
      response times, the interactions with and the outcomes for people in crisis were
      some of the benefits shown when compared with usual services. CONCLUSIONS: The
      pilot showed that a partnership involving mental health and police services in
      Melbourne, Australia could be replicated based on international models. Initial
      data supported improvements compared with usual care. Further data collection
      regarding usual care and this new model is required to confirm observed benefits.

PMID- 26224697
TI  - Assessing and managing suicidal patients in the emergency department.
AB  - OBJECTIVE: The objective of this article is to set out consensus guidelines for
      the assessment and management of "suicidal patients" in the emergency department.
      CONCLUSIONS: Clinicians should be respectful and reassuring. They should review
      old notes, conduct a full history and examination, and talk to friends, family
      and any practitioners already involved in the patient's care. Management should
      be guided, where possible, by the patient's preferences, not by notions of risk.
      Every negotiated management plan and its rationale should be carefully
      documented.

PMID- 26224698
TI  - Delays in accessing electroconvulsive therapy: a comparison between two urban and
      two rural populations in Australia.
AB  - OBJECTIVE: A comparison of the timing, rates and characteristics of
      electroconvulsive therapy use between urban and rural populations. METHOD: The
      medical records of patients who received an acute course of electroconvulsive
      therapy at two rural and two urban psychiatric hospitals in New South Wales
      (NSW), Australia, in 2010 were reviewed retrospectively. Main outcome measures
      were the time from symptom onset, diagnosis and admission to commencing
      electroconvulsive therapy. Rates of use of electroconvulsive therapy were also
      compared between rural and urban hospitals using NSW statewide data. RESULTS:
      There was a significant delay in the time it took for rural patients to receive
      electroconvulsive therapy compared with urban patients when measured both from
      the time of symptom onset and from when they received a diagnosis. There were
      corresponding delays in the time taken for rural patients to be admitted to
      hospital compared with urban patients. There was no difference in the time it
      took to commence electroconvulsive therapy once a patient was admitted to
      hospital. NSW statewide urban-rural comparisons showed rates of electroconvulsive
      therapy treatment were significantly higher in urban hospitals. CONCLUSIONS:
      Patients in rural areas receive electroconvulsive therapy later in their acute
      illness due to delays in being admitted to hospital. The rate of use of
      electroconvulsive therapy also differs geographically.

PMID- 26224699
TI  - An innovative community organizing campaign to improve mental health and
      wellbeing among Pacific Island youth in South Auckland, New Zealand.
AB  - OBJECTIVE: To examine whether being an organizer in a community organizing
      program improves personal agency and self-reported mental health outcomes among
      low-income Pacific Island youth in Auckland, New Zealand. METHOD: Counties
      Manukau Health initiated a community organizing campaign led and run by Pacific
      Island youth. We used interviews, focus groups and pre- and post-campaign surveys
      to examine changes among 30 youths as a result of the campaign. RESULTS: Ten
      youths completed both pre- and post-campaign surveys. Eleven youths participated
      in focus groups, and four in interviews. Overall, youths reported an increased
      sense of agency and improvements to their mental health. CONCLUSIONS: Community
      organizing has potential as a preventive approach to improving mental health and
      developing agency over health among disempowered populations.

PMID- 26224700
TI  - Improving quality of a rural CAMHS service using the Choice and Partnership
      Approach.
AB  - OBJECTIVE: This study outlines the service issues and adjustments associated with
      the implementation of Choice and Partnership Approach (CAPA) into a rural Child
      and Adolescent Mental Health Service (CAMHS). METHOD: A mixed-methods approach
      examined the impacts of the CAPA implementation. A qualitative review of the
      minutes from team and implementation group meetings illustrated themes according
      to 11 key CAPA components. Quantitative internal audit data illustrated waiting
      list times. RESULTS: Findings showed that inclusive language has replaced the
      traditional, pathology-driven psychiatric discourse, though this has been met
      with mixed response from CAMHS clinicians, service users and referrers. Data also
      showed that a waiting list for clinician allocation has been eliminated, and the
      waiting time between the referral date and the first face-to-face contact has
      decreased from 63.9 days to 10.7 days. CONCLUSION: A modified CAPA Choice
      appointment system has allowed quick access without a waiting list, in line with
      government guidelines. A full-booking system and focussed, goal-oriented
      interventions has led to lower caseloads and optimum use of CAMHS clinician
      skillsets.

PMID- 26224701
TI  - Immunophenotype of Spontaneous Hematolymphoid Tumors Occurring in Young and Aging
      Female CD-1 Mice. [Corrected].
AB  - A few reports indicated the incidence of hematolymphoid neoplasms in old CD-1
      mice, but the cellular lineage of CD-1 mouse neoplasms has not been published. In
      this study, immunohistochemistry (IHC) was used to characterize the cellular
      lineage of spontaneous hematolymphoid neoplasms arising in 24 young female CD-1
      mice used as health-monitoring sentinels and 32 aging female CD-1 mice used as
      controls in 80-week carcinogenesis studies. Lymphoblastic lymphomas of T-cell and
      B-cell lineage were common in mice aged 12 months or less, whereas a wide range
      of non-lymphoblastic B-cell lymphomas and lymphoblastic B-cell lymphomas were
      common in mice >12-mo-old. Renal hyaline droplets positive for lysozyme were
      observed in aged mice with a histiocytic-associated large B-cell lymphoma (HA
      BCL) and a myeloid leukemia. Endogenous ecotropic mouse leukemia virus (MuLV)
      genes have been recovered from CD-1 mice, but MuLV protein expression has not
      been previously demonstrated. We reported for the first time the expression of a
      MuLV protein p30 by IHC in lymphomas and some normal tissues of both young and
      aging CD-1 mice. This report should help to differentiate spontaneous lymphomas
      and leukemias in CD-1 mice from those induced by chemicals and other methods. 

PMID- 26224702
TI  - NICE issues draft guideline on end of life care.

PMID- 26224703
TI  - Comparative Genomics of a Bacterivorous Green Alga Reveals Evolutionary
      Causalities and Consequences of Phago-Mixotrophic Mode of Nutrition.
AB  - Cymbomonas tetramitiformis-a marine prasinophyte-is one of only a few green algae
      that still retain an ancestral particulate-feeding mechanism while harvesting
      energy through photosynthesis. The genome of the alga is estimated to be 850 Mb
      1.2 Gb in size-the bulk of which is filled with repetitive sequences-and is
      annotated with 37,366 protein-coding gene models. A number of unusual metabolic
      pathways (for the Chloroplastida) are predicted for C. tetramitiformis, including
      pathways for Lipid-A and peptidoglycan metabolism. Comparative analyses of the
      predicted peptides of C. tetramitiformis to sets of other eukaryotes revealed
      that nonphagocytes are depleted in a number of genes, a proportion of which have
      known function in feeding. In addition, our analysis suggests that obligatory
      phagotrophy is associated with the loss of genes that function in biosynthesis of
      small molecules (e.g., amino acids). Further, C. tetramitiformis and at least one
      other phago-mixotrophic alga are thus unique, compared with obligatory
      heterotrophs and nonphagocytes, in that both feeding and small molecule synthesis
      related genes are retained in their genomes. These results suggest that early,
      ancestral host eukaryotes that gave rise to phototrophs had the capacity to
      assimilate building block molecules from inorganic substances (i.e.,
      prototrophy). The loss of biosynthesis genes, thus, may at least partially
      explain the apparent lack of instances of permanent incorporation of
      photosynthetic endosymbionts in later-divergent, auxotrophic eukaryotic lineages,
      such as metazoans and ciliates. 

PMID- 26224704
TI  - A Genome-Wide Landscape of Retrocopies in Primate Genomes.
AB  - Gene duplication is a key factor contributing to phenotype diversity across and
      within species. Although the availability of complete genomes has led to the
      extensive study of genomic duplications, the dynamics and variability of gene
      duplications mediated by retrotransposition are not well understood. Here, we
      predict mRNA retrotransposition and use comparative genomics to investigate their
      origin and variability across primates. Analyzing seven anthropoid primate
      genomes, we found a similar number of mRNA retrotranspositions (~7,500
      retrocopies) in Catarrhini (Old Word Monkeys, including humans), but a surprising
      large number of retrocopies (~10,000) in Platyrrhini (New World Monkeys), which
      may be a by-product of higher long interspersed nuclear element 1 activity in
      these genomes. By inferring retrocopy orthology, we dated most of the primate
      retrocopy origins, and estimated a decrease in the fixation rate in recent
      primate history, implying a smaller number of species-specific retrocopies.
      Moreover, using RNA-Seq data, we identified approximately 3,600 expressed
      retrocopies. As expected, most of these retrocopies are located near or within
      known genes, present tissue-specific and even species-specific expression
      patterns, and no expression correlation to their parental genes. Taken together,
      our results provide further evidence that mRNA retrotransposition is an active
      mechanism in primate evolution and suggest that retrocopies may not only
      introduce great genetic variability between lineages but also create a large
      reservoir of potentially functional new genomic loci in primate genomes. 

PMID- 26224705
TI  - Environmental variability uncovers disruptive effects of species' interactions on
      population dynamics.
AB  - How species respond to changes in environmental variability has been shown for
      single species, but the question remains whether these results are transferable
      to species when incorporated in ecological communities. Here, we address this
      issue by analysing the same species exposed to a range of environmental
      variabilities when (i) isolated or (ii) embedded in a food web. We find that all
      species in food webs exposed to temporally uncorrelated environments (white
      noise) show the same type of dynamics as isolated species, whereas species in
      food webs exposed to positively autocorrelated environments (red noise) can
      respond completely differently compared with isolated species. This is owing to
      species following their equilibrium densities in a positively autocorrelated
      environment that in turn enables species-species interactions to come into play.
      Our results give new insights into species' response to environmental variation.
      They especially highlight the importance of considering both species'
      interactions and environmental autocorrelation when studying population dynamics
      in a fluctuating environment. 

PMID- 26224706
TI  - Exposure to static electric fields leads to changes in biogenic amine levels in
      the brains of Drosophila.
AB  - Natural and anthropogenic static electric fields are commonly found in the
      environment and can have both beneficial and harmful effects on many animals.
      Here, we asked how the fruitfly responds to these fields and what the
      consequences of exposure are on the levels of biogenic amines in the brain. When
      given a choice in a Y-tube bioassay Drosophila avoided electric fields, and the
      greater the field strength the more likely Drosophila were to avoid it. By
      comparing wild-type flies, flies with wings surgically removed and vestigial
      winged flies we found that the presence of intact wings was necessary to produce
      avoidance behaviour. We also show that Coulomb forces produced by electric fields
      physically lift excised wings, with the smaller wings of males being raised by
      lower field strengths than larger female wings. An analysis of neurochemical
      changes in the brains showed that a suite of changes in biogenic amine levels
      occurs following chronic exposure. Taken together we conclude that physical
      movements of the wings are used by Drosophila in generating avoidance behaviour
      and are accompanied by changes in the levels of amines in the brain, which in
      turn impact on behaviour. 

PMID- 26224707
TI  - Isolation by resistance across a complex coral reef seascape.
AB  - A detailed understanding of the genetic structure of populations and an accurate
      interpretation of processes driving contemporary patterns of gene flow are
      fundamental to successful spatial conservation management. The field of seascape
      genetics seeks to incorporate environmental variables and processes into analyses
      of population genetic data to improve our understanding of forces driving genetic
      divergence in the marine environment. Information about barriers to gene flow
      (such as ocean currents) is used to define a resistance surface to predict the
      spatial genetic structure of populations and explain deviations from the widely
      applied isolation-by-distance model. The majority of seascape approaches to date
      have been applied to linear coastal systems or at large spatial scales (more than
      250 km), with very few applied to complex systems at regional spatial scales
      (less than 100 km). Here, we apply a seascape genetics approach to a peripheral
      population of the broadcast-spawning coral Acropora spicifera across the Houtman
      Abrolhos Islands, a high-latitude complex coral reef system off the central coast
      of Western Australia. We coupled population genetic data from a panel of
      microsatellite DNA markers with a biophysical dispersal model to test whether
      oceanographic processes could explain patterns of genetic divergence. We
      identified significant variation in allele frequencies over distances of less
      than 10 km, with significant differentiation occurring between adjacent sites but
      not between the most geographically distant ones. Recruitment probabilities
      between sites based on simulated larval dispersal were projected into a measure
      of resistance to connectivity that was significantly correlated with patterns of
      genetic divergence, demonstrating that patterns of spatial genetic structure are
      a function of restrictions to gene flow imposed by oceanographic currents. This
      study advances our understanding of the role of larval dispersal on the fine
      scale genetic structure of coral populations across a complex island system and
      applies a methodological framework that can be tailored to suit a variety of
      marine organisms with a range of life-history characteristics.

PMID- 26224709
TI  - A photoactivatable green-fluorescent protein from the phylum Ctenophora.

PMID- 26224708
TI  - Costs of CRISPR-Cas-mediated resistance in Streptococcus thermophilus.
AB  - CRISPR-Cas is a form of adaptive sequence-specific immunity in microbes. This
      system offers unique opportunities for the study of coevolution between bacteria
      and their viral pathogens, bacteriophages. A full understanding of the
      coevolutionary dynamics of CRISPR-Cas requires knowing the magnitude of the cost
      of resisting infection. Here, using the gram-positive bacterium Streptococcus
      thermophilus and its associated virulent phage 2972, a well-established model
      system harbouring at least two type II functional CRISPR-Cas systems, we obtained
      different fitness measures based on growth assays in isolation or in pairwise
      competition. We measured the fitness cost associated with different components of
      this adaptive immune system: the cost of Cas protein expression, the constitutive
      cost of increasing immune memory through additional spacers, and the conditional
      costs of immunity during phage exposure. We found that Cas protein expression is
      particularly costly, as Cas-deficient mutants achieved higher competitive
      abilities than the wild-type strain with functional Cas proteins. Increasing
      immune memory by acquiring up to four phage-derived spacers was not associated
      with fitness costs. In addition, the activation of the CRISPR-Cas system during
      phage exposure induces significant but small fitness costs. Together these
      results suggest that the costs of the CRISPR-Cas system arise mainly due to the
      maintenance of the defence system. We discuss the implications of these results
      for the evolution of CRISPR-Cas-mediated immunity. 

PMID- 26224710
TI  - A spatial theory for characterizing predator-multiprey interactions in
      heterogeneous landscapes.
AB  - Trophic interactions in multiprey systems can be largely determined by prey
      distributions. Yet, classic predator-prey models assume spatially homogeneous
      interactions between predators and prey. We developed a spatially informed theory
      that predicts how habitat heterogeneity alters the landscape-scale distribution
      of mortality risk of prey from predation, and hence the nature of predator
      interactions in multiprey systems. The theoretical model is a spatially explicit,
      multiprey functional response in which species-specific advection-diffusion
      models account for the response of individual prey to habitat edges. The model
      demonstrates that distinct responses of alternative prey species can alter the
      consequences of conspecific aggregation, from increasing safety to increasing
      predation risk. Observations of threatened boreal caribou, moose and grey wolf
      interacting over 378 181 km(2) of human-managed boreal forest support this
      principle. This empirically supported theory demonstrates how distinct responses
      of apparent competitors to landscape heterogeneity, including to human
      disturbances, can reverse density dependence in fitness correlates. 

PMID- 26224712
TI  - The extended Price equation quantifies species selection on mammalian body size
      across the Palaeocene/Eocene Thermal Maximum.
AB  - Species selection, covariation of species' traits with their net diversification
      rates, is an important component of macroevolution. Most studies have relied on
      indirect evidence for its operation and have not quantified its strength relative
      to other macroevolutionary forces. We use an extension of the Price equation to
      quantify the mechanisms of body size macroevolution in mammals from the latest
      Palaeocene and earliest Eocene of the Bighorn and Clarks Fork Basins of Wyoming.
      Dwarfing of mammalian taxa across the Palaeocene/Eocene Thermal Maximum (PETM),
      an intense, brief warming event that occurred at approximately 56 Ma, has been
      suggested to reflect anagenetic change and the immigration of small bodied
      mammals, but might also be attributable to species selection. Using previously
      reconstructed ancestor-descendant relationships, we partitioned change in mean
      mammalian body size into three distinct mechanisms: species selection operating
      on resident mammals, anagenetic change within resident mammalian lineages and
      change due to immigrants. The remarkable decrease in mean body size across the
      warming event occurred through anagenetic change and immigration. Species
      selection also was strong across the PETM but, intriguingly, favoured larger
      bodied species, implying some unknown mechanism(s) by which warming events affect
      macroevolution. 

PMID- 26224711
TI  - Pervasive and strong effects of plants on soil chemistry: a meta-analysis of
      individual plant 'Zinke' effects.
AB  - Plant species leave a chemical signature in the soils below them, generating fine
      scale spatial variation that drives ecological processes. Since the publication
      of a seminal paper on plant-mediated soil heterogeneity by Paul Zinke in 1962, a
      robust literature has developed examining effects of individual plants on their
      local environments (individual plant effects). Here, we synthesize this work
      using meta-analysis to show that plant effects are strong and pervasive across
      ecosystems on six continents. Overall, soil properties beneath individual plants
      differ from those of neighbours by an average of 41%. Although the magnitudes of
      individual plant effects exhibit weak relationships with climate and latitude,
      they are significantly stronger in deserts and tundra than forests, and weaker in
      intensively managed ecosystems. The ubiquitous effects of plant individuals and
      species on local soil properties imply that individual plant effects have a role
      in plant-soil feedbacks, linking individual plants with biogeochemical processes
      at the ecosystem scale. 

PMID- 26224713
TI  - Life-history evolution at the molecular level: adaptive amino acid composition of
      avian vitellogenins.
AB  - Avian genomes typically encode three distinct vitellogenin (VTG) egg yolk
      proteins (VTG1, VTG2 and VTG3), which arose by gene duplication prior to the most
      recent common ancestor of birds. Analysis of VTG sequences from 34 avian species
      in a phylogenetic framework supported the hypothesis that VTG amino acid
      composition has co-evolved with embryo incubation time. Embryo incubation time
      was positively correlated with the proportions of dietary essential amino acids
      (EAAs) in VTG1 and VTG2, and with the proportion of sulfur-containing amino acids
      in VTG3. These patterns were seen even when only semi-altricial and/or altricial
      species were considered, suggesting that the duration of embryo incubation is a
      major selective factor on the amino acid composition of VTGs, rather than
      developmental mode alone. The results are consistent with the hypothesis that the
      level of EAAs provided to the egg represents an adaptation to the loss of amino
      acids through breakdown over the course of incubation and imply that life-history
      phenotypes and VTG amino acid composition have co-evolved throughout the
      evolutionary history of birds. 

PMID- 26224715
TI  - Children's radiology services lack specialist input, audit finds.

PMID- 26224714
TI  - Vestibular migraine in multicenter neurology clinics according to the appendix
      criteria in the third beta edition of the International Classification of
      Headache Disorders.
AB  - BACKGROUND: Vestibular migraine (VM), the common term for recurrent vestibular
      symptoms with migraine features, has been recognized in the appendix criteria of
      the third beta edition of the International Classification of Headache Disorders
      (ICHD-3beta). We applied the criteria for VM in a prospective, multicenter
      headache registry study. METHODS: Nine neurologists enrolled consecutive patients
      visiting outpatient clinics for headache. The presenting headache disorder and
      additional VM diagnoses were classified according to the ICHD-3beta. The rates of
      patients diagnosed with VM and probable VM using consensus criteria were
      assessed. RESULTS: A total of 1414 patients were enrolled. Of 631 migraineurs, 65
      were classified with VM (10.3%) and 16 with probable VM (2.5%). Accompanying
      migraine subtypes in VM were migraine without aura (66.2%), chronic migraine
      (29.2%), and migraine with aura (4.6%). Probable migraine (75%) was common in
      those with probable VM. The most common vestibular symptom was head motion
      induced dizziness with nausea in VM and spontaneous vertigo in probable VM. The
      clinical characteristics of VM did not differ from those of migraine without VM.
      CONCLUSION: We diagnosed VM in 10.3% of first-visit migraineurs in neurology
      clinics using the ICHD-3beta. Applying the diagnosis of probable VM can increase
      the identification of VM.

PMID- 26224716
TI  - A novel and sensitive assay for heme oxygenase activity.
AB  - Heme oxygenase (HO) is a renoprotective protein in the microsome that degrades
      heme and produces biliverdin. Biliverdin is then reduced to a potent antioxidant
      bilirubin by biliverdin reductase in the cytosol. Because HO activity does not
      necessarily correlate with HO mRNA or protein levels, a reliable assay is needed
      to determine HO activity. Spectrophotometric measurement is tedious and requires
      a relatively large amount of kidney samples. Moreover, bilirubin is unstable and
      spontaneously oxidized to biliverdin in vitro. We developed a novel and sensitive
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify
      biliverdin to measure HO activity in mice. Biliverdin and its internal standard,
      a deuterated biliverdin-d4, have MS/MS fragments with m/z transitions of 583 to
      297 and 587 to 299, respectively. We prepared lysates of mouse kidneys, and added
      excess hemin, NADPH, and bilirubin oxidase to convert all bilirubin produced to
      biliverdin. After 30-min incubation at 37 or 4 degrees C, the samples were
      analyzed by LC-MS/MS. The difference in the amount of biliverdin between the two
      temperatures is HO activity. Treating mice with cobalt protoporphyrin, which
      induces the expression of HO, increased HO activity as determined by biliverdin
      production. Measuring the production of biliverdin using LC-MS/MS is a more
      sensitive and specific way to determine HO activity than the spectrophotometric
      method and allows the detection of subtle changes in renal or other HO activity. 

PMID- 26224719
TI  - A Case of Culture: Defendant Gender and Juror Decision-Making.
AB  - The purpose of this study was to investigate the use of cultural evidence toward
      an automatism defense, and whether such evidence would be detrimental or
      beneficial to a male versus a female defendant. U.S. participants ( N = 208),
      recruited via Amazon's Mechanical Turk, read a fictional spousal homicide case in
      which the defendant claimed to have blacked out during the crime. We manipulated
      the gender of the defendant and whether a culture-specific issue was claimed to
      have precipitated the defendant's blackout. ANOVAs revealed that cultural
      evidence positively affected perceived credibility for the female defendant,
      whereas there were no differences for the male defendant. Results also
      demonstrated that when cultural evidence was presented, the female defendant was
      seen as less in control of her actions than was the male defendant. Furthermore,
      lower credibility and higher perceived defendant control predicted harsher
      verdict decisions. This investigation may aid scholars in discussing concerns
      regarding a clash between multicultural and feminist objectives in the courtroom.

PMID- 26224717
TI  - NBCe1 expression is required for normal renal ammonia metabolism.
AB  - The mechanisms regulating proximal tubule ammonia metabolism are incompletely
      understood. The present study addressed the role of the proximal tubule
      basolateral electrogenic Na(+)-coupled bicarbonate cotransporter (NBCe1; Slc4a4)
      in renal ammonia metabolism. We used mice with heterozygous and homozygous NBCe1
      gene deletion and compared these mice with their wild-type littermates. Because
      homozygous NBCe1 gene deletion causes 100% mortality before day 25, we studied
      mice at day 8 (+/-1 day). Both heterozygous and homozygous gene deletion caused a
      gene dose-related decrease in serum bicarbonate. The ability to lower urinary pH
      was intact, and even accentuated, with NBCe1 deletion. However, in contrast to
      the well-known effect of metabolic acidosis to increase urinary ammonia
      excretion, NBCe1 deletion caused a gene dose-related decrease in ammonia
      excretion. There was no identifiable change in proximal tubule structure by light
      microscopy. Examination of proteins involved in renal ammonia metabolism showed
      decreased expression of phosphate-dependent glutaminase and phosphoenolpyruvate
      carboxykinase, key enzymes in proximal tubule ammonia generation, and increased
      expression of glutamine synthetase, which recycles intrarenal ammonia and
      regenerates glutamine. Expression of key proteins involved in ammonia transport
      outside of the proximal tubule (rhesus B glycoprotein and rhesus C glycoprotein)
      was not significantly changed by NBCe1 deletion. We conclude from these findings
      that NBCe1 expression is necessary for normal proximal tubule ammonia metabolism.

PMID- 26224720
TI  - Longitudinal Predictors of Child Sexual Abuse in a Large Community-Based Sample
      of South African Youth.
AB  - Sexual abuse has severe negative impacts on children's lives, but little is known
      about risk factors for sexual abuse victimization in sub-Saharan Africa. This
      study examined prospective predictors of contact sexual abuse in a random
      community-based sample of children aged 10 to 17 years ( N = 3,515, 56.6% female)
      in South Africa. Self-report questionnaires using validated scales were completed
      at baseline and at 1-year follow-up (96.8% retention rate). Cross-sectional and
      longitudinal associations between hypothesized factors and sexual abuse were
      examined. For girls, previous sexual abuse (odds ratio [OR] = 3.44, 95%
      confidence interval [CI] = [2.03, 5.60]), baseline school dropout (OR = 2.76, 95%
      CI = [1.00, 6.19]), and physical assault in the community (OR = 2.17, 95% CI =
      [1.29, 3.48]) predicted sexual abuse at follow-up. Peer social support (OR =
      0.84, 95% CI = [0.74, 0.98]) acted as a protective factor. Previous contact
      sexual abuse was the strongest predictor of subsequent sexual abuse
      victimization. In addition, peer support moderated the relationship between
      baseline assault and subsequent sexual abuse. For boys, no longitudinal
      predictors for sexual abuse victimization were identified. These results indicate
      that the most vulnerable girls-those not in school and with a history of
      victimization-are at higher risk for sexual abuse victimization. High levels of
      peer support reduced the risk of sexual abuse victimization and acted as a
      moderator for those who had experienced physical assault within the community.
      Interventions to reduce school drop-out rates and revictimization may help
      prevent contact sexual abuse of girls in South Africa.

PMID- 26224718
TI  - Renal denervation for the treatment of resistant hypertension: review and
      clinical perspective.
AB  - When introduced clinically 6 years ago, renal denervation was thought to be the
      solution for all patients whose blood pressure could not be controlled by
      medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated
      great magnitudes of blood pressure reduction within 6 mo of the procedure and
      were based on a number of assumptions that may not have been true, including
      strict adherence to medication and absence of white-coat hypertension. The
      SYMPLICITY HTN-3 trial controlled for all possible factors believed to influence
      the outcome, including the addition of a sham arm, and ultimately proved the
      demise of the initial overly optimistic expectations. This trial yielded a much
      lower blood pressure reduction compared with the previous SYMPLICITY trials.
      Since its publication in 2014, there have been many analyses to try and
      understand what accounted for the differences. Of all the variables examined that
      could influence blood pressure outcomes, the extent of the denervation procedure
      was determined to be inadequate. Beyond this, the physiological mechanisms that
      account for the heterogeneous fall in arterial pressure following renal
      denervation remain unclear, and experimental studies indicate dependence on more
      than simply reduced renal sympathetic activity. These and other related issues
      are discussed in this paper. Our perspective is that renal denervation works if
      done properly and used in the appropriate patient population. New studies with
      new approaches and catheters and appropriate controls will be starting later this
      year to reassess the efficacy and safety of renal denervation in humans. 

PMID- 26224721
TI  - Performance Evaluations and Victim Satisfaction With State Compensation for
      Violent Crime: A Prospective Study.
AB  - Satisfaction with a particular good or service represents an affective state in
      response to an individual's evaluation of the performance of that good or
      service. This evaluation involves a comparison between perceived actual
      performance and prior expectations. The current study used this theoretical idea
      to study violent crime victims' levels of satisfaction with services provided by
      a Dutch state compensation scheme. One hundred and seventy-seven victims of
      violent crime who had applied for compensation from the Dutch Violent Offences
      Compensation Fund (DVOCF) participated in two brief telephone interviews: one
      before receipt of the fund's decision upon their request for compensation and one
      after receipt of that decision. Based on the theories of distributive and
      procedural justice, measurement of prior expectations was differentiated in
      expectations about receipt of compensation, treatment by fund workers, and
      information provision. Results suggested that satisfaction with the DVOCF
      depended on fulfillment of expectations about treatment by fund workers and
      information provision, but not on fulfillment of expectations about receipt of
      compensation. Other predictors of victim satisfaction were as follows: duration
      of the application procedure, approval upon request for compensation, and
      satisfaction assessed during the first interview. Results were discussed in light
      of theory, policy implications, study limitations, and future research.

PMID- 26224723
TI  - Medicare could save up to $16bn if allowed to negotiate drug prices, paper finds.

PMID- 26224722
TI  - Comparison of the Effects of Elaeagnus angustifolia Flower Capsule and Sildenafil
      Citrate Tablet on Anxiety Resulting From Sexual Dysfunction in Women Referring to
      the Selected Clinics of Shiraz University of Medical Sciences.
AB  - Dissatisfaction from sexual relationships can result in deprivation as well as
      problems, such as depression, anxiety, and destruction of family's mental health.
      One hundred twenty-five women (18 to 40 years) who suffered from hypoactive
      sexual desire disorder were divided into Elaeagnus angustifolia flower (4.5 g g
      daily for 35 days), sildenafil citrate tablet (50 mg for 4 weeks), and control
      groups. The study data were collected using the Female Sexual Function Index and
      Spielberger's questionnaire and measurement of thyroid-stimulating hormone and
      prolactin hormone. In the Elaeagnus angustifolia group, the mean score of state
      and trait anxiety decreased after the intervention. In the sildenafil citrate
      group also, the mean score of state anxiety decreased from 22.15 +/- 4.98 to 20.1
      +/- 5.15 (P = .001) and that of trait anxiety decreased from 23.07 +/- 4.44 to
      21.55 +/- 4.82 (P = .002) after the intervention. Consumption of sildenafil
      citrate tablet was effective in reduction of the mean score of anxiety resulting
      from sexual dysfunction. 

PMID- 26224724
TI  - Involving Communities in Deciding What Benefits They Receive in Multinational
      Research.
AB  - There is wide agreement that communities in lower-income countries should benefit
      when they participate in multinational research. Debate now focuses on how and to
      what extent these communities should benefit. This debate has identified
      compelling reasons to reject the claim that whatever benefits a community agrees
      to accept are necessarily fair. Yet, those who conduct clinical research may
      conclude from this rejection that there is no reason to involve communities in
      the process of deciding how they benefit. Against this possibility, the present
      manuscript argues that involving host communities in this process helps to
      promote four important goals: (1) protecting host communities, (2) respecting
      host communities, (3) promoting transparency, and (4) enhancing social value. 

PMID- 26224725
TI  - TPP1 deficiency: Rare cause of isolated childhood-onset progressive ataxia.

PMID- 26224726
TI  - Education Research: Changing medical student perceptions of dementia: an arts
      centered experience.
AB  - BACKGROUND: Medical students' comfort level working with dementia is poorly
      understood, and may impact subsequent experiences with patients and caregivers.
      Early experiences that take place in a nonmedical setting may allow students to
      gain a more comprehensive understanding of quality of life and disease management
      in everyday life. METHODS: We studied Columbia University preclinical medical
      students' perceptions of dementia relative to attending a nonclinical art
      centered, museum-based experience designed for people with dementia and their
      caregivers. Participants individually attended a single 90-minute museum-based
      art-centered program designed to engage patients with dementia and caregivers;
      programs are attended by 6-10 patient-caregiver dyads and led by trained museum
      educators at existing New York City sites including The Metropolitan Museum of
      Art, The Cloisters, The Studio Museum in Harlem, and The New-York Historical
      Society. RESULTS: The Dementia Attitudes Scale (DAS) was administered before and
      after the intervention (least favorable = 20, neutral = 80, most favorable =
      140). A total of 19 students completed baseline and postintervention DAS. At
      baseline, DAS mean = 97.4 (SD = 11.2). To limit bias of taking the test, 9
      students completed a second preintervention DAS (>=1 week apart); among these,
      DAS increased from 95.7 (SD = 7.7) to 98.7 (SD = 7.4) (p = 0.09). Following the
      intervention, DAS favorably and significantly increased to 105.8 (SD = 11.0) (p
      <= 0.01 for all comparisons, paired-samples t test); greater differences were
      identified in comfort than knowledge of dementia. CONCLUSIONS: Although further
      study is warranted to confirm findings, given the increasing availability of such
      programs, it is reasonable to consider inclusion of these alongside other
      nonclinical programs that are already part of medical school curricula.

PMID- 26224728
TI  - Gene sleuthing in pyridoxine-dependent epilepsy.

PMID- 26224727
TI  - Response to endovascular reperfusion is not time-dependent in patients with
      salvageable tissue.
AB  - OBJECTIVE: To evaluate whether time to treatment modifies the effect of
      endovascular reperfusion in stroke patients with evidence of salvageable tissue
      on MRI. METHODS: Patients from the Diffusion and Perfusion Imaging Evaluation for
      Understanding Stroke Evolution 2 (DEFUSE 2) cohort study with a perfusion
      diffusion target mismatch were included. Reperfusion was defined as a decrease in
      the perfusion lesion volume of at least 50% between baseline and early follow-up.
      Good functional outcome was defined as a modified Rankin Scale score <=2 at day
      90. Lesion growth was defined as the difference between the baseline and the
      early follow-up diffusion-weighted imaging lesion volumes. RESULTS: Among 78
      patients with the target mismatch profile (mean age 66 +/- 16 years, 54% women),
      reperfusion was associated with increased odds of good functional outcome
      (adjusted odds ratio 3.7, 95% confidence interval 1.2-12, p = 0.03) and
      attenuation of lesion growth (p = 0.02). Time to treatment did not modify these
      effects (p value for the time * reperfusion interaction is 0.6 for good
      functional outcome and 0.3 for lesion growth). Similarly, in the subgroup of
      patients with reperfusion (n = 46), time to treatment was not associated with
      good functional outcome (p = 0.2). CONCLUSION: The association between
      endovascular reperfusion and improved functional and radiologic outcomes is not
      time-dependent in patients with a perfusion-diffusion mismatch. Proof that
      patients with mismatch benefit from endovascular therapy in the late time window
      should come from a randomized placebo-controlled trial.

PMID- 26224729
TI  - Art and Alzheimer dementia: a museum experience for patients may benefit medical
      students.

PMID- 26224730
TI  - Intragenic deletions of ALDH7A1 in pyridoxine-dependent epilepsy caused by Alu
      Alu recombination.
AB  - OBJECTIVE: To investigate the role of intragenic deletions of ALDH7A1 in patients
      with clinical and biochemical evidence of pyridoxine-dependent epilepsy but only
      a single identifiable mutation in ALDH7A1. METHODS: We designed a custom
      oligonucleotide array with high-density probe coverage across the ALDH7A1 gene.
      We performed array comparative genomic hybridization in 6 patients with clinical
      and biochemical evidence of pyridoxine-dependent epilepsy but only a single
      detectable mutation in ALDH7A1 by sequence analysis. RESULTS: We found partial
      deletions of ALDH7A1 in 5 of 6 patients. Breakpoint analysis reveals that the
      deletions are likely a result of Alu-Alu recombination in all cases. The density
      of Alu elements within introns of ALDH7A1 suggests susceptibility to recurrent
      rearrangement. CONCLUSION: Patients with clinical pyridoxine-dependent epilepsy
      and a single identifiable mutation in ALDH7A1 warrant further investigation for
      copy number changes involving the ALHD7A1 gene.

PMID- 26224731
TI  - Elevation of Kynurenine Metabolites in Rat Liver and Serum: A Potential
      Additional Mechanism of the Alcohol Aversive and Anti-cancer Effects of
      Disulfiram?
AB  - AIMS: The tryptophan metabolites 3-hydroxykynurenine (3-HK) and 3
      hydroxyanthranilic acid (3-HAA) inhibit the liver mitochondrial low Km aldehyde
      dehydrogenase and possess alcohol-aversive and immunosuppressant properties. As
      the disulfiram (DS) metabolite carbon disulphide activates enzymes forming 3-HK
      and 3-HAA, we investigated if repeated disulfiram treatment increases the hepatic
      and serum levels of these 2 metabolites. METHODS: Livers and sera of male Wistar
      rats were analysed for tryptophan and kynurenine metabolites after repeated DS
      treatment for 7 days. RESULTS: DS increased liver and serum [3-HK] and [3-HAA]
      possibly by increasing the flux of tryptophan down the hepatic kynurenine pathway
      and activation of kynurenine hydroxylase and kynureninase. CONCLUSIONS: We
      provisionally suggest that elevation of some kynurenine metabolites may be an
      additional mechanism of the alcohol-aversive and anticancer effects of
      disulfiram.

PMID- 26224732
TI  - The effects of pentobarbital, ketamine-pentobarbital and ketamine-xylazine
      anesthesia in a rat myocardial ischemic reperfusion injury model.
AB  - To achieve reliable experimental data, the side-effects of anesthetics should be
      eliminated. Since anesthetics exert a variety of effects on hemodynamic data and
      incidence of arrhythmias, the selection of anesthetic agents in a myocardial
      ischemic reperfusion injury model is very important. The present study was
      performed to compare hemodynamic variables, the incidence of ventricular
      arrhythmias, and infarct size during 30 min of ischemia and 120 min of
      reperfusion in rats using pentobarbital, ketamine-pentobarbital or ketamine
      xylazine anaesthesia. A total of 30 rats were randomly divided into three groups.
      In group P, pentobarbital (60 mg/kg, intraperitoneally [IP]) was used solely; in
      group K-P, ketamine and pentobarbital (50 and 30 mg/kg, respectively, IP) were
      used in combination; and in group K-X, ketamine and xylazine (75 and 5 mg/kg,
      respectively, IP) were also used in combination. Hemodynamic data and occurrence
      of ventricular arrhythmias were recorded throughout the experiments. The ischemic
      area was measured by triphenyltetrazolium chloride staining. The combination of
      ketamine-xylazine caused bradycardia and hypotension. The greatest reduction in
      mean arterial blood pressure during ischemia was in the P group. The most
      stability in hemodynamic parameters during ischemia and reperfusion was in the K
      P group. The infarct size was significantly less in the K-X group. Whereas none
      of the rats anesthetized with ketamine-xylazine fibrillated during ischemia,
      ventricular fibrillation occurred in 57% of the animals anesthetized with
      pentobarbital or ketamine-pentobarbital. Because it offers the most stable
      hemodynamic parameters, it is concluded that the ketamine-pentobarbital
      anesthesia combination is the best anesthesia in a rat ischemia reperfusion
      injury model. 

PMID- 26224733
TI  - A Novel Aerosol Foam Formulation of Calcipotriol and Betamethasone Has No Impact
      on HPA Axis and Calcium Homeostasis in Patients With Extensive Psoriasis
      Vulgaris.
AB  - BACKGROUND: Fixed combination calcipotriol 50 ug/g (Cal; as hydrate) plus
      betamethasone 0.5 mg/g (as dipropionate; BD) has been formulated in an innovative
      aerosol foam. OBJECTIVE: To assess systemic safety of Cal/BD aerosol foam.
      METHODS: In a multicentre, single-arm, open-label, maximal-use systemic-exposure
      trial, adult patients with moderate to severe, extensive psoriasis (15%-30% of
      body surface area, including >=30% of scalp) applied Cal/BD foam once daily.
      Endpoints were week 4 abnormal adrenocorticotropic hormone (ACTH) challenge test
      and change in albumin-corrected serum calcium, 24-hour urinary calcium excretion,
      and urinary calcium-creatinine ratio. RESULTS: 35 patients reaching week 4
      exhibited normal ACTH responses. At week 4, changes in calcium homeostasis were
      minor and not clinically relevant; no patients experienced elevations above
      normal. Disease severity generally improved, and 49% of patients achieved
      treatment success according to the Physician's Global Assessment of Disease
      Severity. CONCLUSION: No clinically relevant HPA axis or calcium homeostasis
      impact was observed with 4 weeks of once-daily Cal/BD foam in patients with
      extensive psoriasis vulgaris.

PMID- 26224734
TI  - Bayesian Nonparametric Inference of Population Size Changes from Sequential
      Genealogies.
AB  - Sophisticated inferential tools coupled with the coalescent model have recently
      emerged for estimating past population sizes from genomic data. Recent methods
      that model recombination require small sample sizes, make constraining
      assumptions about population size changes, and do not report measures of
      uncertainty for estimates. Here, we develop a Gaussian process-based Bayesian
      nonparametric method coupled with a sequentially Markov coalescent model that
      allows accurate inference of population sizes over time from a set of
      genealogies. In contrast to current methods, our approach considers a broad class
      of recombination events, including those that do not change local genealogies. We
      show that our method outperforms recent likelihood-based methods that rely on
      discretization of the parameter space. We illustrate the application of our
      method to multiple demographic histories, including population bottlenecks and
      exponential growth. In simulation, our Bayesian approach produces point estimates
      four times more accurate than maximum-likelihood estimation (based on the sum of
      absolute differences between the truth and the estimated values). Further, our
      method's credible intervals for population size as a function of time cover 90%
      of true values across multiple demographic scenarios, enabling formal hypothesis
      testing about population size differences over time. Using genealogies estimated
      with ARGweaver, we apply our method to European and Yoruban samples from the 1000
      Genomes Project and confirm key known aspects of population size history over the
      past 150,000 years. 

PMID- 26224735
TI  - Genotype-Frequency Estimation from High-Throughput Sequencing Data.
AB  - Rapidly improving high-throughput sequencing technologies provide unprecedented
      opportunities for carrying out population-genomic studies with various organisms.
      To take full advantage of these methods, it is essential to correctly estimate
      allele and genotype frequencies, and here we present a maximum-likelihood method
      that accomplishes these tasks. The proposed method fully accounts for
      uncertainties resulting from sequencing errors and biparental chromosome sampling
      and yields essentially unbiased estimates with minimal sampling variances with
      moderately high depths of coverage regardless of a mating system and structure of
      the population. Moreover, we have developed statistical tests for examining the
      significance of polymorphisms and their genotypic deviations from Hardy-Weinberg
      equilibrium. We examine the performance of the proposed method by computer
      simulations and apply it to low-coverage human data generated by high-throughput
      sequencing. The results show that the proposed method improves our ability to
      carry out population-genomic analyses in important ways. The software package of
      the proposed method is freely available from https://github.com/Takahiro
      Maruki/Package-GFE. 

PMID- 26224737
TI  - ASSESSMENT OF EYE LENS DOSES IN INTERVENTIONAL RADIOLOGY: A SIMULATION IN
      LABORATORY CONDITIONS.
AB  - As workers in interventional radiology belong to one of the most occupationally
      exposed groups, methods for sufficiently accurate quantification of their
      external exposure are sought. The objective of the authors' experiment was to
      investigate the relations between eye lens dose and Hp(10), Hp(3) or Hp(0.07)
      values measured with a conventional whole-body personal thermoluminescence
      dosemeter (TLD). Conditions of occupational exposure during common interventional
      procedures were simulated in laboratory. An anthropomorphic phantom represented a
      physician. The TLDs were fixed to the phantom in different locations that are
      common for purposes of personal dosimetry. In order to monitor the dose at the
      eye lens level during the exposures, a special thermoluminescence eye dosemeter
      was fixed to the phantom's temple. Correlations between doses measured with the
      whole-body and the eye dosemeters were found. There are indications that
      personnel in interventional radiology do not need to be unconditionally equipped
      with additional eye dosemeters, especially if an appropriate whole-body dosimetry
      system has been already put into practice. 

PMID- 26224736
TI  - Lesion-Induced Mutation in the Hyperthermophilic Archaeon Sulfolobus
      acidocaldarius and Its Avoidance by the Y-Family DNA Polymerase Dbh.
AB  - Hyperthermophilic archaea offer certain advantages as models of genome
      replication, and Sulfolobus Y-family polymerases Dpo4 (S. solfataricus) and Dbh
      (S. acidocaldarius) have been studied intensively in vitro as biochemical and
      structural models of trans-lesion DNA synthesis (TLS). However, the genetic
      functions of these enzymes have not been determined in the native context of
      living cells. We developed the first quantitative genetic assays of replication
      past defined DNA lesions and error-prone motifs in Sulfolobus chromosomes and
      used them to measure the efficiency and accuracy of bypass in normal and dbh(-)
      strains of Sulfolobus acidocaldarius. Oligonucleotide-mediated transformation
      allowed low levels of abasic-site bypass to be observed in S. acidocaldarius and
      demonstrated that the local sequence context affected bypass specificity; in
      addition, most erroneous TLS did not require Dbh function. Applying the technique
      to another common lesion, 7,8-dihydro-8-oxo-deoxyguanosine (8-oxo-dG), revealed
      an antimutagenic role of Dbh. The efficiency and accuracy of replication past 8
      oxo-dG was higher in the presence of Dbh, and up to 90% of the Dbh-dependent
      events inserted dC. A third set of assays, based on phenotypic reversion, showed
      no effect of Dbh function on spontaneous -1 frameshifts in mononucleotide tracts
      in vivo, despite the extremely frequent slippage at these motifs documented in
      vitro. Taken together, the results indicate that a primary genetic role of Dbh is
      to avoid mutations at 8-oxo-dG that occur when other Sulfolobus enzymes replicate
      past this lesion. The genetic evidence that Dbh is recruited to 8-oxo-dG raises
      questions regarding the mechanism of recruitment, since Sulfolobus spp. have
      eukaryotic-like replisomes but no ubiquitin. 

PMID- 26224738
TI  - Dose evaluation for foetal computed tomography with a 320-row unit in wide-volume
      mode and an 80-row unit in helical scanning mode: a phantom study.
AB  - The purpose of this study was to evaluate the maternal and foetal effective doses
      during foetal computed tomography (CT) and to compare the radiation dose, dose
      profile and image noise on 80-row CT in helical scanning mode and 320-row CT in
      wide-volume scanning mode. The radiation doses were measured using
      thermoluminescent dosemeters implanted at various organ sites of an
      anthropomorphic pregnant phantom. The foetal doses in the 320-row multi-detector
      CT (MDCT) and 80-row MDCT units were higher than the volume CT dose index
      (CTDIvol). The dose profile in the 320-row MDCT overlapped in two places but
      showed no overlap in the 80-row MDCT. There were no significant differences in
      image noise between the two scanning modes. The foetal dose evaluation by CTDIvol
      may underestimate the foetal radiation risk. When using the wide-volume mode,
      operators must take into account the number of scans and overlap between
      volumetric sections. 

PMID- 26224739
TI  - Shielding activation of petawatt laser facilities in Romania: a FLUKA preliminary
      evaluation.
AB  - The FLUKA 2011.2c code was used to evaluate the activity induced in the
      irradiation chamber walls by secondary charged particles emitted during the
      interaction of 1 petawatt laser beam with the targets. The results have shown
      that, even in the most conservative approaches, i.e. 300 and 100 MeV secondary
      electrons and protons, respectively, the maximum equivalent dose rate, at 1 cm in
      front of the chamber wall, 1 min after the end of irradiation, was of ~23 nSv h(
      1). Three minutes later, it falls at ~60 pSv h(-1), negligible with respect to
      the environmental radiation background of 90-110 nSv h(-1), as reported for
      Romania. 

PMID- 26224742
TI  - A Longitudinal Causal Analysis of Impact Made by Collaborative Engagement and
      Service Receipt on Likelihood of Substantiated Re-Report.
AB  - In a temporal-ordering causal analysis, we explored impacts of parent's receipt
      of services and caseworker-parent collaborative engagement on substantiated child
      maltreatment re-report. Our sample of 2,368 parents came from the National Survey
      of Child and Adolescent Well-Being. Using generalized estimating equations, we
      found likelihood of substantiated re-report to drop significantly in association
      with collaborative engagement, length of current in-home spell, and family
      income. In turn, parental alcohol dependence, initial substantiated sexual
      maltreatment, and prior in-home spells were linked to increased likelihood.
      Practice implications are discussed. 

PMID- 26224743
TI  - Child Protection Investigations in Out-of-Home Care: Perpetrators, Victims, and
      Contexts.
AB  - Keeping children safe in out-of-home care requires an understanding of the
      contexts under which maltreatment occurs. This study examines how maltreatment
      investigations differ across four settings (nonrelative foster, informal kinship,
      formal kinship, and congregate care). I focus on four elements of maltreatment:
      the perpetrator's role (e.g., out-of-home caregiver and peer), maltreatment type,
      probability of substantiation, and victim characteristics. I use statewide
      Wisconsin administrative data in years 2005-2012, which has an analytic sample of
      over 96,000 placements. Data are analyzed using descriptive statistics and multi
      level logistic regression. Alleged maltreatment is not uncommon in out-of-home
      care-the total investigation rate ranged from 5% (congregate care) to 15%
      (informal kinship care). Four percent of all placements were investigated for
      maltreatment by an out-of-home caregiver, of which 9% were substantiated.
      Maltreatment by peers (siblings or other foster children) was investigated in 1%
      of all placements, of which 20% were substantiated. Neglect was the most commonly
      alleged maltreatment type in informal kinship care, whereas physical abuse was
      most commonly alleged in all other placement types. Children who were female,
      Black, or between ages 6 and 10 experienced heightened risk of maltreatment in
      out-of-home care. 

PMID- 26224744
TI  - Photo Quiz. Pulmonary Nodule and Subcutaneous Abscess in a 71-Year-Old Patient
      With Multiple Myeloma.

PMID- 26224746
TI  - Micro-skills of group formulations in care settings: Working with expressions of
      staff distress.
AB  - The help of specialist clinicians is often sought to advise staff in residential
      and nursing care homes about how to work with people with dementia whose
      behaviour is challenging. The Newcastle Model ( James, 2011 ) is a framework and
      a process developed to help care staff understand and improve their care of this
      group. The model emphasises the use of sharing information with staff to develop
      effective care plans. In the Shared Formulation Sessions characteristic of the
      Newcastle Model, clinicians take the role of a group facilitator, helping the
      staff reach a consensus about what needs to change. These sessions can be
      difficult to manage as intra and inter-group processes emerge and the group
      express their anxieties. This paper aims to explore the processes that might be
      in play Shared Formulation Sessions and to suggest ways in which the facilitator
      might approach this to manage effective collaborative working.

PMID- 26224747
TI  - Return on investment (ROI) modelling in public health: strengths and limitations.

PMID- 26224748
TI  - How Robustly Does Cannabis Use Associate to College Grades? Findings From Two
      Cohorts.
AB  - Along with recent changes in cannabis legalization and decriminalization, there
      has been an increasing amount of attention aimed at cannabis use and outcomes in
      college. Although some amount of cannabis use might be expected under theories of
      collegiate identity development, public health research indicates that cannabis
      use ultimately associates with negative vocational outcomes. To examine how
      cannabis use associates with college grade point average specifically, we
      surveyed n = 1,080 full-time college students and a replication sample of n =
      590. Results showed that even after accounting for other measures of student
      identity formation and drug use, increased cannabis use was robustly associated
      with lower grade point average. Future research should examine the mechanisms
      underlying this association. Nevertheless, while laws and attitudes toward
      cannabis evolve, initiatives to decrease college use should continue.

PMID- 26224749
TI  - Extracts of Fruits and Vegetables Activate the Antioxidant Response Element in
      IMR-32 Cells.
AB  - BACKGROUND: The biological effects of antioxidant nutrients are mediated in part
      by activation of antioxidant response elements (AREs) on genes for enzymes
      involved in endogenous pathways that prevent free radical damage. Traditional
      approaches for identifying antioxidant molecules in foods, such as total phenolic
      compound (TP) content or oxygen radical absorption capacity (ORAC), do not
      measure capacity to activate AREs. OBJECTIVES: The goal of this study was to
      develop an assay to assess the ARE activation capacity of fruit and vegetable
      extracts and determine whether such capacity was predicted by TP content and/or
      ORAC activity. METHODS: Fruits and vegetables were homogenized, extracted with
      acidified ethanol, lyophilized, and resuspended in growth medium. Human IMR-32
      neuroblastoma cells, transfected with an ARE-firefly luciferase reporter, were
      exposed to extracts for 5 h. Firefly luciferase was normalized to constitutively
      expressed Renilla luciferase with tertiary butylhydroquinone (tBHQ) as a positive
      control. TP content and ORAC activity were measured for each extract. Relations
      between TPs and ORAC and ARE activity were determined. RESULTS: A total of 107 of
      134 extracts tested significantly activated the ARE-luciferase reporter from 1.2-
      to 58-fold above that of the solvent control (P < 0.05) in human IMR-32 cells.
      ARE activity, TP content, and ORAC ranked higher in peels than in associated
      flesh. Despite this relation, ARE activity did not correlate with TP content
      (Spearman rho = 0.05, P = 0.57) and only modestly but negatively correlated with
      ORAC (Spearman rho = -0.24, P < 0.01). Many extracts activated the ARE more than
      predicted by the TP content or ORAC. CONCLUSIONS: The ARE reporter assay
      identified many active fruit and vegetable extracts in human IMR-32 cells. There
      are components of fruits and vegetables that activate the ARE but are not
      phenolic compounds and are low in ORAC. The ARE-luciferase reporter assay is
      likely a better predictor of the antioxidant benefits of fruits and vegetables
      than TP or ORAC.

PMID- 26224750
TI  - The Skeletal Muscle Anabolic Response to Plant- versus Animal-Based Protein
      Consumption.
AB  - Clinical and consumer market interest is increasingly directed toward the use of
      plant-based proteins as dietary components aimed at preserving or increasing
      skeletal muscle mass. However, recent evidence suggests that the ingestion of the
      plant-based proteins in soy and wheat results in a lower muscle protein synthetic
      response when compared with several animal-based proteins. The possible lower
      anabolic properties of plant-based protein sources may be attributed to the lower
      digestibility of plant-based sources, in addition to greater splanchnic
      extraction and subsequent urea synthesis of plant protein-derived amino acids
      compared with animal-based proteins. The latter may be related to the relative
      lack of specific essential amino acids in plant- as opposed to animal-based
      proteins. Furthermore, most plant proteins have a relatively low leucine content,
      which may further reduce their anabolic properties when compared with animal
      proteins. However, few studies have actually assessed the postprandial muscle
      protein synthetic response to the ingestion of plant proteins, with soy and wheat
      protein being the primary sources studied. Despite the proposed lower anabolic
      properties of plant vs. animal proteins, various strategies may be applied to
      augment the anabolic properties of plant proteins. These may include the
      following: 1) fortification of plant-based protein sources with the amino acids
      methionine, lysine, and/or leucine; 2) selective breeding of plant sources to
      improve amino acid profiles; 3) consumption of greater amounts of plant-based
      protein sources; or 4) ingesting multiple protein sources to provide a more
      balanced amino acid profile. However, the efficacy of such dietary strategies on
      postprandial muscle protein synthesis remains to be studied. Future research
      comparing the anabolic properties of a variety of plant-based proteins should
      define the preferred protein sources to be used in nutritional interventions to
      support skeletal muscle mass gain or maintenance in both healthy and clinical
      populations. 

PMID- 26224751
TI  - Jejunal Casein Feeding Is Followed by More Rapid Protein Digestion and Amino Acid
      Absorption When Compared with Gastric Feeding in Healthy Young Men.
AB  - BACKGROUND: Dietary protein is required to attenuate the loss of muscle mass and
      to support recovery during a period of hospitalization. Jejunal feeding is
      preferred over gastric feeding in patients who are intolerant of gastric feeding.
      However, the impact of gastric vs. jejunal feeding on postprandial dietary
      protein digestion and absorption kinetics in vivo in humans remains largely
      unexplored. OBJECTIVE: We compared the impact of gastric vs. jejunal feeding on
      subsequent dietary protein digestion and amino acid (AA) absorption in vivo in
      healthy young men. METHODS: In a randomized crossover study design, 11 healthy
      young men (aged 21 +/- 2 y) were administered 25 g specifically produced
      intrinsically l-[1-(13)C]phenylalanine-labeled intact casein via a nasogastric
      and a nasojejunal tube placed ~30 cm distal to the ligament of Treitz. Protein
      was provided in a 240-mL solution administered over a 65-min period in both
      feeding regimens. Blood samples were collected during the 7-h postprandial period
      to assess the increase in plasma AA concentrations and dietary protein-derived
      plasma l-[1-(13)C]phenylalanine enrichment. RESULTS: Jejunal feeding compared
      with gastric feeding resulted in higher peak plasma phenylalanine, leucine, total
      essential AA (EAA), and total AA concentrations (all P < 0.05). This was
      attributed to a more rapid release of dietary protein-derived AAs into the
      circulation, as evidenced by a higher peak plasma l-[1-(13)C]phenylalanine
      enrichment concentration (2.9 +/- 0.2 vs. 2.2 +/- 0.2 mole percent excess; P <
      0.05). The total postprandial plasma AA incremental area under the curve and time
      to peak did not differ after jejunal vs. gastric feeding. Plasma insulin
      concentrations increased to a greater extent after jejunal feeding when compared
      with gastric feeding (275 +/- 38 vs. 178 +/- 38 pmol/L; P < 0.05). CONCLUSIONS:
      Jejunal feeding of intact casein is followed by more rapid protein digestion and
      AA absorption when compared with gastric feeding in healthy young men. The
      greater postprandial increase in circulating EAA concentrations may allow a more
      robust increase in muscle protein synthesis rate after jejunal vs. gastric casein
      feeding. This trial was registered at trialregister.nl as NTR2801.

PMID- 26224752
TI  - Effectiveness of Prompts on Fourth-Grade Children's Dietary Recall Accuracy
      Depends on Retention Interval and Varies by Gender.
AB  - BACKGROUND: Dietary recall accuracy is related to retention interval (RI) (i.e.,
      time between to-be-reported meals and the interview), and possibly to prompts. To
      the best of our knowledge, no study has evaluated their combined effect.
      OBJECTIVE: The combined influence of RI and prompts on children's recall accuracy
      was investigated in this study. Two RIs [short (prior-24-h recall obtained in
      afternoon) and long (previous-day recall obtained in morning)] were crossed with
      4 prompts [forward (distant-to-recent), meal-name (breakfast, lunch, etc.), open
      (no instructions), and reverse (recent-to-distant)], creating 8 conditions.
      METHODS: Fourth-grade children (n = 480; 50% girls) were randomly selected from
      consenting children at 10 schools in 4 districts in a southern state during 3
      school years (2011-2012, 2012-2013, and 2013-2014). Each child was observed
      eating school-provided breakfast and lunch, and interviewed one time under 1 of
      the 8 conditions. Condition assignment was constrained so that each had 60
      children (30 girls). Accuracy measures were food-item omission and intrusion
      rates, and energy correspondence rate and inflation ratio. For each measure,
      linear models determined effects of RI, prompt, gender, and interactions (2-way,
      3-way); race/ethnicity, school year, and district were control variables.
      RESULTS: RI (P values < 0.015) and prompt (P values < 0.005) were significant for
      all 4 accuracy measures. RI * prompt (P values < 0.001) was significant for 3
      accuracy measures (not intrusion rate). Prompt * gender (P = 0.005) was
      significant for omission rate. RI * prompt * gender was significant for intrusion
      rate and inflation ratio (P values < 0.001). For the short vs. long RI across
      prompts and genders, accuracy was better by 33-50% for each accuracy measure.
      CONCLUSIONS: To obtain the most accurate recalls possible from children, studies
      should be designed to use a short rather than long RI. Prompts affect children's
      recall accuracy, although the effectiveness of different prompts depends on RI
      and varies by gender: at a short RI, the choice of prompts has little systematic
      effect on accuracy, whereas at a long RI, reverse prompts may elicit the most
      accurate recalls.

PMID- 26224754
TI  - Unequal Inequalities: The Stratification of the Use of Formal Care Among Older
      Europeans.
AB  - Objectives: The general aim of the article is to incorporate the stratification
      perspective into the study of (long-term) care systems. In particular, 3 issues
      are investigated: the extents to which (a) personal and family resources
      influence the likelihood of using formal care in later life; (b) the unequal
      access to formal care is mediated by differences in the availability of informal
      support; (c) the relationship between individuals' resources and the use of
      formal care in old age varies across care regimes and is related to the
      institutional design of long-term care policies. Method: Data from Waves 1 and 2
      of the Survey of Health, Ageing and Retirement in Europe for 4 countries:
      Denmark, Germany, France, and Italy, and population aged at least 65 (N = 9,824)
      were used. Population-averaged logit models were used. Results: Logit models
      revealed that in terms of access to formal care: an individual's educational
      level plays a limited role; family networks function similarly across the
      countries studied; in general, financial wealth does not have a significant
      effect; there is a positive relation between income and the use of formal care in
      Germany and Italy, and no significant relation in France and Denmark; home
      ownership has a negative effect in Germany and Denmark. On accounting for
      informal care, inequality associated with individuals' economic resources remains
      substantially unaltered. Discussion: The study shows that care systems based on
      services provision grant higher access to formal care and create lower
      inequalities. Moreover, countries where cash-for-care programs and family
      responsibilities are more important register inequalities in the use of formal
      care. Access to informal care does not mediate the distribution of formal care.

PMID- 26224753
TI  - DNA hypermethylation in hyperhomocysteinemia contributes to abnormal
      extracellular matrix metabolism in the kidney.
AB  - Hyperhomocysteinemia (HHcy) is prevalent in patients with chronic kidney disease
      (CKD) and end-stage renal disease (ESRD). Emerging studies suggest that
      epigenetic mechanisms contribute to the development and progression of fibrosis
      in CKD. HHcy and its intermediates are known to alter the DNA methylation
      pattern, which is a critical regulator of epigenetic information. In this study,
      we hypothesized that HHcy causes renovascular remodeling by DNA hypermethylation,
      leading to glomerulosclerosis. We also evaluated whether the DNA methylation
      inhibitor, 5-aza-2'-deoxycytidine (5-Aza) could modulate extracellular matrix
      (ECM) metabolism and reduce renovascular fibrosis. C57BL/6J (wild-type) and
      cystathionine-beta-synthase (CBS(+/-)) mice, treated without or with 5-Aza (0.5
      mg/kg body weight, i.p.), were used. CBS(+/-) mice showed high plasma Hcy levels,
      hypertension, and significant glomerular and arteriolar injury. 5-Aza treatment
      normalized blood pressure and reversed renal injury. CBS(+/-) mice showed global
      hypermethylation and up-regulation of DNA methyltransferase-1 and -3a.
      Methylation-specific PCR showed an imbalance between matrix metalloproteinase
      (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and -2 and also
      increased collagen and galectin-3 expression. 5-Aza reduced abnormal DNA
      methylation and restored the MMP-9/TIMP-1, -2 balance. In conclusion, our data
      suggest that during HHcy, abnormal DNA methylation and an imbalance between MMP-9
      and TIMP-1 and -2 lead to ECM remodeling and renal fibrosis.

PMID- 26224755
TI  - Age Effects in Adaptive Criterion Learning.
AB  - OBJECTIVE: Although prior work has examined age-related changes to criterion
      placement and flexibility, no study tested these constructs through a paradigm
      that employs adaptive feedback to encourage specific criterion changes. The goal
      of this study was to assess age differences in how young and older adults adapt
      and shift criteria in recognition memory decisions based on trial-by-trial
      feedback. METHOD: Young and older adults completed an adaptive criterion learning
      paradigm. Over 3 study/test cycles, a biased feedback technique at test
      encouraged more liberal or strict responding by false-positive feedback toward
      false alarms or misses. RESULTS: Older adults were more conservative than young,
      even when feedback first encouraged a liberal response bias, and older adults
      adaptively placed criteria in response to biased feedback, much like young
      adults. After first being encouraged to respond conservatively, older adults
      shifted criteria less than young when feedback encouraged more lenient
      responding. DISCUSSION: These findings evidence labile adaptive criteria
      placement and criteria shifting with age. However, age-related tendencies toward
      conservative response biases may limit the extent to which criteria can be
      shifted in a lenient direction.

PMID- 26224756
TI  - Importance of Numeracy as a Risk Factor for Elder Financial Exploitation in a
      Community Sample.
AB  - OBJECTIVES: To examine the role of numeracy, or comfort with numbers, as a
      potential risk factor for financial elder exploitation in a community sample.
      METHOD: Individually administered surveys were given to 201 independent,
      community-dwelling adults aged 60 and older. Risk for financial elder
      exploitation was assessed using the Older Adult Financial Exploitation Measure
      (OAFEM). Other variables of interest included numeracy, executive functioning,
      and other risk factors identified from the literature. Assessments were completed
      individually at the Wood Lab at Scripps College in Claremont, CA and neighboring
      community centers. RESULTS: After controlling for other variables, including
      education, lower numeracy was related to higher scores on the OAFEM consistent
      with higher risk for financial exploitation. Self-reported physical and mental
      health, male gender, and younger age were also related to increased risk.
      CONCLUSIONS: Results indicated that numeracy is a significant risk factor for
      elder financial exploitation after controlling for other commonly reported
      variables. These findings are consistent with the broader literature relating
      numeracy to wealth and debt levels and extend them to the area of elder financial
      exploitation.

PMID- 26224757
TI  - Response-Conflict Moderates the Cognitive Control of Episodic and Contextual Load
      in Older Adults.
AB  - OBJECTIVES: Decline in cognitive control is one of the primary cognitive changes
      in normal aging. Reaching a consensus regarding the nature of these age-related
      changes, however, is complicated by the complexity of cognitive control as a
      construct. METHODS: Healthy older and younger adults participated in a
      multifactorial test of cognitive control. Within participants, the procedure
      varied as a function of the amount contextual load, episodic load, and response
      conflict load present. RESULTS: We found that older adults showed impaired
      performance relative to younger adults. We also found, however, that the response
      selection process underlying the response-conflict manipulation was a major
      moderator of age-related differences in both the contextual and episodic load
      conditions-suggesting a hierarchical organization. DISCUSSION: These findings are
      consistent with previous findings, suggesting that deficits in cognitive control
      in older adults are directly related to the resolution of response-conflict and
      that other apparent deficits may be derivative upon the more basic response
      conflict related deficit.

PMID- 26224758
TI  - Age Differences in Interpreting Ambiguous Situations: The Effects of Content
      Themes and Depressed Mood.
AB  - OBJECTIVES: This study aimed to investigate the boundary conditions of the
      positivity effect on appraisals of ambiguous situations across content themes and
      emotional states. We differentiated the processes of interpretation generation
      and selection to see whether older adults recognize negative aspects of ambiguous
      situations but tend to select positive interpretations. METHOD: Seventy-six
      younger and 67 older adults went through sad and neutral mood inductions and
      completed ambiguous situation tasks. Participants were asked to generate
      interpretations and select one as the most likely explanation for each scenario.
      RESULTS: Results demonstrated that compared with younger adults, older adults
      selected less negative interpretations across content themes but generated fewer
      negative interpretations in interpersonal but not in health situations. Depressed
      mood led to more negative interpretations at both generation and selection for
      younger adults but not older adults. CONCLUSIONS: Our results showed that
      thematic factors had an effect on the positivity effect on interpretation
      generation, but regardless of content themes, older adults selected a less
      negative interpretation as the most likely, despite knowing alternative negative
      explanations. The positivity effect remained for older adults in high trait and
      state depressed mood. Together these findings are consistent with the pattern of
      older adults' tendency to maximize emotional well-being through less negative
      interpretations of ambiguous situations.

PMID- 26224759
TI  - Greater Perceived Age Discrimination in England than the United States: Results
      from HRS and ELSA.
AB  - OBJECTIVES: We examined cross-national differences in perceptions of age
      discrimination in England and the United States. Under the premise that the
      United States has had age discrimination legislation in place for considerably
      longer than England, we hypothesized that perceptions of age discrimination would
      be lower in the United States. METHODS: We analyzed data from two nationally
      representative studies of aging, the U.S. Health and Retirement Study (n = 4,818)
      and the English Longitudinal Study of Ageing (n = 7,478). Respondents aged 52
      years and older who attributed any experiences of discrimination to their age
      were treated as cases of perceived age discrimination. We used multivariable
      logistic regression to estimate the odds ratios of experiencing perceived age
      discrimination in relation to selected sociodemographic factors. RESULTS:
      Perceptions of age discrimination were significantly higher in England than the
      United States, with 34.8% of men and women in England reporting age
      discrimination compared with 29.1% in the United States. Associations between
      perceived age discrimination and older age and lower levels of household wealth
      were observed in both countries, but we found differences between England and the
      United States in the relationship between perceived age discrimination and
      education. DISCUSSION: Our study revealed that levels of perceived age
      discrimination are lower in the United States than England and are less socially
      patterned. This suggests that differing social and political circumstances in the
      two countries may have an important role to play.

PMID- 26224760
TI  - Improving the Quality of Outpatient Diabetes Care Using an Information Management
      System: Results From the Observational VISION Study.
AB  - BACKGROUND: This study aimed to evaluate the effects of information management
      system (IMS) use with individuals with type 1 and type 2 diabetes who were
      treated in outpatient settings. METHODS: In this 7-month, prospective,
      observational study, 965 adults with diabetes, mean (SD) baseline HbA1c
      8.61(1.2)% (70.6[13.1] mmol/mol), were recruited from 132 outpatient care centers
      in Germany and Denmark. HbA1c was measured at baseline, month 4, and month 7. IMS
      reports were generated from uploaded self-monitored blood glucose data and
      therapy adjustments were documented at months 1 and 4. Hypoglycemic events were
      documented. RESULTS: Mean (SD) HbA1c decreased from baseline in type 1 and type 2
      diabetes patients at month 4 (-0.61[1.03]% (-6.7[11.3] mmol/mol), n = 213; 
      0.88[1.22]% (-9.6[13.3] mmol/mol), n = 589, respectively) and month 7 (
      0.64[1.02]% (-7.0[11.1] mmol/mol), n = 219; -0.93[1.27]% (-10.2[13.9] mmol/mol),
      n = 594, respectively), all P < .0001, with no increase in hypoglycemic events.
      Therapy was adjusted in 106(42.7)% type 1 and 349(52.4)% type 2 diabetes patients
      at months 1 and 105(42.3)% type 1 and 282(42.3)% type 2 diabetes patients at
      month 4. Physicians used IMS reports to make therapy adjustments in 90% of
      patients at month 1 and 86% of patients at month 4. CONCLUSIONS: Integration of
      the IMS into outpatient care facilitates significant improvements in glycemic
      control.

PMID- 26224761
TI  - Accuracy Evaluation of Two Blood Glucose Monitoring Systems Following ISO
      15197:2013.

PMID- 26224762
TI  - Multisite Study of an Implanted Continuous Glucose Sensor Over 90 Days in
      Patients With Diabetes Mellitus.
AB  - BACKGROUND: Continuous glucose monitoring (CGM), which enables real-time glucose
      display and trend information as well as real-time alarms, can improve glycemic
      control and quality of life in patients with diabetes mellitus. Previous reports
      have described strategies to extend the useable lifetime of a single sensor from
      1-2 weeks to 28 days. The present multisite study describes the characterization
      of a sensing platform achieving 90 days of continuous use for a single, fully
      implanted sensor. METHOD: The Senseonics CGM system is composed of a long-term
      implantable glucose sensor and a wearable smart transmitter. Study subjects
      underwent subcutaneous implantation of sensors in the upper arm. Eight-hour
      clinic sessions were performed every 14 days, during which sensor glucose values
      were compared against venous blood lab reference measurements collected every 15
      minutes using mean absolute relative differences (MARDs). RESULTS: All subjects
      (mean +/- standard deviation age: 43.5 +/- 11.0 years; with 10 sensors inserted
      in men and 14 in women) had type 1 diabetes mellitus. Most (22 of 24) sensors
      reported glucose values for the entire 90 days. The MARD value was 11.4 +/- 2.7%
      (range, 8.1-19.5%) for reference glucose values between 40-400 mg/dl. There was
      no significant difference in MARD throughout the 90-day study (P = .31). No
      serious adverse events were noted. CONCLUSIONS: The Senseonics CGM, composed of
      an implantable sensor, external smart transmitter, and smartphone app, is the
      first system that uses a single sensor for continuous display of accurate glucose
      values for 3 months.

PMID- 26224764
TI  - Aging Together: Caring Relations in Families of Adults With Intellectual
      Disabilities.
AB  - Purpose of the Study: To examine the dynamics of caring relations in older
      families that include an adult with Intellectual Disabilities (ID). To date,
      there has been very little research exploring the experiences of aging families
      of community-dwelling adults with ID. Design and Methods: An exploratory,
      qualitative study was conducted in British Columbia, Canada. Eight participants
      were recruited through purposive sampling. In-depth, semistructured interviews
      were conducted to explore the experience of aging concurrently with a community
      dwelling relative with ID. Data were analyzed using a thematic approach. Results:
      Three main themes emerged: (a) Recognizing the Changes of Aging, (b)
      Strengthening Connections, and (c) Planning for the Future. Implications: Aging
      concurrently with a community-dwelling relative with ID is a unique experience
      for older adults and challenges traditional views of familial caring relations.
      These relationships are characterized by evolving patterns of care and exchange.
      There is also a sense of urgency to securing future care arrangements for the
      adult relative with ID. Advanced care-planning is complicated by the adult with
      ID' understanding of death and dying. Family caregiving policies and practices
      that take into account the complexities of these relationships are needed.

PMID- 26224763
TI  - Certified Nursing Assistants Balancing Family Caregiving Roles: Health Care
      Utilization Among Double- and Triple-Duty Caregivers.
AB  - PURPOSE OF THE STUDY: This study examines how certified nursing assistants (CNAs)
      balancing family caregiving roles-child care (double-duty child caregivers),
      elder care (double-duty elder caregivers), and both child and elder care (triple
      duty caregivers)-utilize health care services relative to nonfamily caregiving
      counterparts (formal-only caregivers). DESIGN AND METHODS: A sample of 884 CNAs
      from the Work, Family and Health Study was drawn on to assess the number of acute
      care (i.e., emergency room or urgent care facility) and other health care (i.e.,
      outpatient treatment or counseling) visits made during the past 6 months.
      RESULTS: Double-duty elder and triple-duty caregivers had higher acute care
      utilization rates than formal-only caregivers. CNAs with and without family
      caregiving roles had similar rates of other health care visits. IMPLICATIONS:
      CNAs providing informal care for older adults have higher acute care visit rates.
      Given the increasing need for family caregivers and the vital importance of the
      health of the nursing workforce for the health of others, future research on how
      double- and triple-duty caregivers maintain their health amidst constant
      caregiving should be a priority.

PMID- 26224766
TI  - Hollow Fiber System Model for Tuberculosis: The European Medicines Agency
      Experience.
AB  - The in vitro hollow fiber system model has been qualified by the European
      Medicines Agency as a methodology for use in support of selection and development
      of antituberculosis regimens. More data are expected to be generated in the
      future to further characterize its value. 

PMID- 26224765
TI  - Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia
      and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale
      and design of the MARLINA-T2DTM trial.
AB  - Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects with
      Renal Disease with LINAgliptin (MARLINA-T2DTM), a multicentre, multinational,
      randomized, double-blind, placebo-controlled, parallel-group, phase 3b clinical
      trial, aims to further define the potential renal effects of dipeptidyl peptidase
      4 inhibition beyond glycaemic control. A total of 350 eligible individuals with
      inadequately controlled type 2 diabetes and evidence of renal disease are planned
      to be randomized in a 1:1 ratio to receive either linagliptin 5 mg or placebo in
      addition to their stable glucose-lowering background therapy for 24 weeks. Two
      predefined main endpoints will be tested in a hierarchical manner: (1) change
      from baseline in glycated haemoglobin and (2) time-weighted average of percentage
      change from baseline in urinary albumin-to-creatinine ratio. Both endpoints are
      sufficiently powered to test for superiority versus placebo after 24 weeks with
      alpha = 0.05. MARLINA-T2DTM is the first of its class to prospectively explore
      both the glucose- and albuminuria-lowering potential of a dipeptidyl peptidase-4
      inhibitor in patients with type 2 diabetes and evidence of renal disease. 

PMID- 26224767
TI  - Systematic Analysis of Hollow Fiber Model of Tuberculosis Experiments.
AB  - BACKGROUND: The in vitro hollow fiber system model of tuberculosis (HFS-TB), in
      tandem with Monte Carlo experiments, was introduced more than a decade ago. Since
      then, it has been used to perform a large number of tuberculosis
      pharmacokinetics/pharmacodynamics (PK/PD) studies that have not been subjected to
      systematic analysis. METHODS: We performed a literature search to identify all
      HFS-TB experiments published between 1 January 2000 and 31 December 2012. There
      was no exclusion of articles by language. Bias minimization was according to
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
      Steps for reporting systematic reviews were followed. RESULTS: There were 22 HFS
      TB studies published, of which 12 were combination therapy studies and 10 were
      monotherapy studies. There were 4 stand-alone Monte Carlo experiments that
      utilized quantitative output from the HFS-TB. All experiments reported drug
      pharmacokinetics, which recapitulated those encountered in humans. HFS-TB studies
      included log-phase growth studies under ambient air, semidormant bacteria at pH
      5.8, and nonreplicating persisters at low oxygen tension of <= 10 parts per
      billion. The studies identified antibiotic exposures associated with optimal kill
      of Mycobacterium tuberculosis and suppression of acquired drug resistance (ADR)
      and informed predictions about optimal clinical doses, expected performance of
      standard doses and regimens in patients, and expected rates of ADR, as well as a
      proposal of new susceptibility breakpoints. CONCLUSIONS: The HFS-TB model offers
      the ability to perform PK/PD studies including humanlike drug exposures, to
      identify bactericidal and sterilizing effect rates, and to identify exposures
      associated with suppression of drug resistance. Because of the ability to perform
      repetitive sampling from the same unit over time, the HFS-TB vastly improves
      statistical power and facilitates the execution of time-to-event analyses and
      repeated event analyses, as well as dynamic system pharmacology mathematical
      models.

PMID- 26224768
TI  - Correlations Between the Hollow Fiber Model of Tuberculosis and Therapeutic
      Events in Tuberculosis Patients: Learn and Confirm.
AB  - BACKGROUND: The hollow fiber system model of tuberculosis (HFS-TB) is designed to
      perform pharmacokinetics/pharmacodynamics (PK/PD) experiments, and hence the
      design of optimal doses and dose schedules for the treatment of tuberculosis. To
      determine if this model is useful for deriving PK/PD data relevant to clinical
      outcomes, we compared its quantitative output to that from clinical trials.
      METHODS: We performed a PubMed search to identify clinical studies performed with
      antituberculosis therapy in which PK/PD data and/or parameters were documented or
      a dose-scheduling study design was employed. The search period was from January
      1943 to December 2012. All clinical studies were published prior to HFS-TB
      experiments. Bias minimization was done according to the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses. Clinical publications were scored
      for quality of evidence, with 1 as the highest score (randomized controlled
      trials or meta-analyses of such studies), and 4 as the lowest score. RESULTS: We
      identified 17 studies that examined the same parameters as in 8 HFS-TB studies.
      Fifteen of 17 studies had a quality-of-evidence score of 1. The sterilizing and
      bactericidal effect rates for isoniazid, rifampin, pyrazinamide, and ethambutol
      were the same in the HFS-TB as in patients. Time to emergence of resistance for
      monotherapy was the same as in patients. The PK/PD indices associated with
      efficacy were the same in HFS-TB as in patients for all drugs examined.
      CONCLUSIONS: The HFS-TB model is highly accurate at identifying optimal drug
      exposures, doses, and dosing schedules for use in the clinic.

PMID- 26224769
TI  - Forecasting Accuracy of the Hollow Fiber Model of Tuberculosis for Clinical
      Therapeutic Outcomes.
AB  - BACKGROUND: The hollow fiber system model of tuberculosis (HFS-TB), in tandem
      with Monte Carlo experiments, represents a drug development tool (DDT) with the
      potential for use to develop tuberculosis treatment regimens. However, the
      predictive accuracy of the HFS-TB, or any other nonclinical DDT such as an animal
      model, has yet to be robustly evaluated. METHODS: To avoid hindsight bias, a
      literature search was performed to identify clinical studies published at least 6
      months after HFS-TB experiments' quantitative predictions. Steps to minimize bias
      and for reporting systematic reviews were applied as outlined in the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses. Publications were
      scored for quality of evidence. Accuracy was calculated using the mean absolute
      percentage error, then summated with weighting assigned by sample size and
      quality-of-evidence score. Given the lack of a gold-standard tuberculosis DDT,
      the forecasting accuracy of a completely unreliable tool was also calculated from
      1000 simulated experiments for a random or "total guesswork" model. RESULTS: The
      quantitative forecasting accuracy (95% confidence interval [CI]) for the "total
      guesswork" model was 15.6% (95% CI, 8.7%-22.5%); bias was -0.1% (95% CI, -2.5% to
      2.2%). Twenty clinical studies were published after HFS-TB experiments predicted
      optimal drug exposures and doses, susceptibility breakpoints, and optimal
      combination regimens. Based on these clinical studies, the predictive accuracy of
      the HFS-TB was 94.4% (95% CI, 84.3%-99.9%), and bias was 1.8% (95% CI, -13.7% to
      6.2%). CONCLUSIONS: The HFS-TB model is highly accurate at forecasting optimal
      drug exposures, doses, and dosing schedules for use in the clinic.

PMID- 26224770
TI  - The Hollow Fiber System Model in the Nonclinical Evaluation of Antituberculosis
      Drug Regimens.

PMID- 26224771
TI  - Strategic Regulatory Evaluation and Endorsement of the Hollow Fiber Tuberculosis
      System as a Novel Drug Development Tool.
AB  - The first nonclinical drug development tool (DDT) advanced by the Critical Path
      to TB Drug Regimens (CPTR) Initiative through a regulatory review process has
      been endorsed by leading global regulatory authorities. DDTs with demonstrated
      predictive accuracy for clinical and microbiological outcomes are needed to
      support decision making. Regulatory endorsement of these DDTs is critical for
      drug developers, as it promotes confidence in their use in Investigational New
      Drug and New Drug Application filings. The in vitro hollow fiber system model of
      tuberculosis (HFS-TB) is able to recapitulate concentration-time profiles
      (exposure) observed in patients for single drugs and combinations, by evaluating
      exposure measures for the ability to kill tuberculosis in different physiologic
      conditions. Monte Carlo simulations make this quantitative output useful to
      inform susceptibility breakpoints, dosage, and optimal combination regimens in
      patients, and to design nonclinical experiments in animal models. The Pre
      Clinical and Clinical Sciences Working Group within CPTR executed an evidence
      based evaluation of the HFS-TB for predictive accuracy. This extensive effort was
      enabled through the collaboration of subject matter experts representing the
      pharmaceutical industry, academia, product development partnerships, and
      regulatory authorities including the Food and Drug Administration (FDA) and the
      European Medicines Agency (EMA). A comprehensive analysis plan following the
      regulatory guidance documents for DDT qualification was developed, followed by
      individual discussions with the FDA and the EMA. The results from the
      quantitative analyses were submitted to both agencies, pursuing regulatory DDT
      endorsement. The EMA Qualification Opinion for the HFS-TB DDT was published 26
      January 2015 (available at:
      http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/doc
      ment_listing_000319.jsp). 

PMID- 26224772
TI  - Minimizing the caliber of myelinated axons by means of nodal constrictions.
AB  - In myelinated axons, most of the voltage-gated ion channels are concentrated at
      the nodes of Ranvier, which are short gaps in the myelin sheath. This arrangement
      leads to saltatory conduction and a larger conduction velocity than in
      nonmyelinated axons. Intriguingly, axons in the peripheral nervous system that
      exceed about 2 MUm in diameter exhibit a characteristic narrowing of the axon at
      nodes that results in a local reduction of the axonal cross-sectional area. The
      extent of constriction increases with increasing internodal axonal caliber,
      reaching a threefold reduction in diameter for the largest axons. In this paper,
      we use computational modeling to investigate the effect of nodal constrictions on
      axonal conduction velocity. For a fixed number of ion channels, we find that
      there is an optimal extent of nodal constriction which minimizes the internodal
      axon caliber that is required to achieve a given target conduction velocity, and
      we show that this is sensitive to the precise geometry of the axon and myelin
      sheath in the flanking paranodal regions. Thus axonal constrictions at nodes of
      Ranvier appear to be a biological adaptation to minimize axonal volume, thereby
      maximizing the spatial and metabolic efficiency of these processes, which can be
      a significant evolutionary constraint. We show that the optimal nodal
      morphologies are relatively insensitive to changes in the number of nodal sodium
      channels. 

PMID- 26224773
TI  - Neural coordination during reach-to-grasp.
AB  - When reaching to grasp, we coordinate how we preshape the hand with how we move
      it. To ask how motor cortical neurons participate in this coordination, we
      examined the interactions between reach- and grasp-related neuronal ensembles
      while monkeys reached to grasp a variety of different objects in different
      locations. By describing the dynamics of these two ensembles as trajectories in a
      low-dimensional state space, we examined their coupling in time. We found
      evidence for temporal compensation across many different reach-to-grasp
      conditions such that if one neural trajectory led in time the other tended to
      catch up, reducing the asynchrony between the trajectories. Granger causality
      revealed bidirectional interactions between reach and grasp neural trajectories
      beyond that which could be attributed to the joint kinematics that were
      consistently stronger in the grasp-to-reach direction. Characterizing cortical
      coordination dynamics provides a new framework for understanding the functional
      interactions between neural populations. 

PMID- 26224774
TI  - Distinct dynamics of ramping activity in the frontal cortex and caudate nucleus
      in monkeys.
AB  - The prefronto-striatal network is involved in many cognitive functions, including
      perceptual decision making and reward-modulated behaviors. For well-trained
      subjects, neural responses frequently show similar patterns in the prefrontal
      cortex and striatum, making it difficult to tease apart distinct regional
      contributions. Here I show that, despite similar mean firing rate patterns,
      prefrontal and striatal responses differ in other temporal dynamics for both
      perceptual and reward-based tasks. Compared with simulation results, the temporal
      dynamics of prefrontal activity are consistent with an accumulation of sensory
      evidence used to solve a perceptual task but not with an accumulation of reward
      context-related information used for the development of a reward bias. In
      contrast, the dynamics of striatal activity is consistent with an accumulation of
      reward context-related information and with an accumulation of sensory evidence
      during early stimulus viewing. These results suggest that prefrontal and striatal
      neurons may have specialized functions for different tasks even with similar
      average activity. 

PMID- 26224775
TI  - Mammalian target of rapamycin is required for phrenic long-term facilitation
      following severe but not moderate acute intermittent hypoxia.
AB  - Phrenic long-term facilitation (pLTF) is a persistent increase in phrenic nerve
      activity after acute intermittent hypoxia (AIH). Distinct cell-signaling cascades
      give rise to pLTF depending on the severity of hypoxemia within hypoxic episodes.
      Moderate AIH (mAIH; three 5-min episodes, PaO2 ~35-55 mmHG) elicits pLTF by a
      serotonin (5-HT)-dependent mechanism that requires new synthesis of brain-derived
      neurotrophic factor (BDNF), activation of its high-affinity receptor (TrkB), and
      ERK MAPK signaling. In contrast, severe AIH (sAIH; three 5-min episodes, PaO2 ~25
      30 mmHG) elicits pLTF by an adenosine-dependent mechanism that requires new TrkB
      synthesis and Akt signaling. Although both mechanisms require spinal protein
      synthesis, the newly synthesized proteins are distinct, as are the neurochemicals
      inducing plasticity (serotonin vs. adenosine). In many forms of neuroplasticity,
      new protein synthesis requires translational regulation via mammalian target of
      rapamycin (mTOR) signaling. Since Akt regulates mTOR activity, we hypothesized
      that mTOR activity is necessary for sAIH- but not mAIH-induced pLTF. Phrenic
      nerve activity in anesthetized, paralyzed, and ventilated rats was recorded
      before, during, and 60 min after mAIH or sAIH. Rats were pretreated with
      intrathecal injections of 20% DMSO (vehicle controls) or rapamycin (0.1 mM, 12
      MUl), a selective mTOR complex 1 inhibitor. Consistent with our hypothesis,
      rapamycin blocked sAIH- but not mAIH-induced pLTF. Thus spinal mTOR activity is
      required for adenosine-dependent (sAIH) but not serotonin-dependent (mAIH) pLTF,
      suggesting that distinct mechanisms regulate new protein synthesis in these forms
      of spinal neuroplasticity. 

PMID- 26224777
TI  - Homotypic synaptic coupling and the cellular bases of gamma oscillatory activity.
AB  - Although the importance of gamma oscillatory activity in brain function is well
      established, the exact contributions of neuron and synapse type remains unclear.
      In their study, Hu and Agmon (J Neurophysiol 114: 624-637, 2015) show that
      precision as well as firing rate dependence of gamma synchrony rely primarily on
      cellular coupling type (chemical, electrical, or dual), rather than properties
      intrinsic to cell type. These findings are discussed with a focus on current
      ramifications and the implications for future research. 

PMID- 26224776
TI  - Maps of interaural delay in the owl's nucleus laminaris.
AB  - Axons from the nucleus magnocellularis form a presynaptic map of interaural time
      differences (ITDs) in the nucleus laminaris (NL). These inputs generate a field
      potential that varies systematically with recording position and can be used to
      measure the map of ITDs. In the barn owl, the representation of best ITD shifts
      with mediolateral position in NL, so as to form continuous, smoothly overlapping
      maps of ITD with iso-ITD contours that are not parallel to the NL border. Frontal
      space (0 degrees ) is, however, represented throughout and thus overrepresented
      with respect to the periphery. Measurements of presynaptic conduction delay,
      combined with a model of delay line conduction velocity, reveal that conduction
      delays can account for the mediolateral shifts in the map of ITD. 

PMID- 26224778
TI  - Neuroligin-2 and the tightrope of excitation/inhibition balance in the prefrontal
      cortex.
AB  - Excitation/inhibition imbalance is implicated in symptoms of neuropsychiatric
      disorders. We discuss a study by Liang et al. (Mol Psychiatry 20: 850-859, 2015)
      demonstrating that the conditional knockout of neuroligin-2, a postsynaptic
      adhesion protein, in the prefrontal cortex of adult mice results in alterations
      in inhibitory synaptic properties. However, behavioral impairments emerged prior
      to the development of detectable changes in excitation/inhibition ratio. This
      suggests there may be network-specific excitation/inhibition ratios, some of
      which are more vulnerable to disruption than others. 

PMID- 26224779
TI  - Mushroom body extrinsic neurons in the honeybee (Apis mellifera) brain integrate
      context and cue values upon attentional stimulus selection.
AB  - Multimodal GABA-immunoreactive feedback neurons in the honeybee brain connecting
      the output region of the mushroom body with its input are expected to tune the
      input to the mushroom body in an experience-dependent way. These neurons are
      known to change their rate responses to learned olfactory stimuli. In this work
      we ask whether these neurons also transmit learned attentional effects during
      multisensory integration. We find that a visual context and an olfactory cue
      change the rate responses of these neurons after learning according to the
      associated values of both context and cue. The learned visual context promotes
      attentional response selection by enhancing olfactory stimulus valuation at both
      the behavioral and the neural level. During a rewarded visual context, bees
      reacted faster and more reliably to a rewarded odor. We interpreted this as the
      result of the observed enhanced neural discharge toward the odor. An unrewarded
      context reduced already low rate responses to the unrewarded odor. In addition to
      stimulus valuation, these feedback neurons generate a neural error signal after
      an incorrect behavioral response. This might act as a learning signal in feedback
      neurons. All of these effects were exclusively found in trials in which the
      animal prepares for a motor response that happens during attentional stimulus
      selection. We discuss possible implications of the results for the feedback
      connections of the mushroom body. 

PMID- 26224780
TI  - Connectivity between the superior colliculus and the amygdala in humans and
      macaque monkeys: virtual dissection with probabilistic DTI tractography.
AB  - It has been suggested that some cortically blind patients can process the
      emotional valence of visual stimuli via a fast, subcortical pathway from the
      superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide
      in vivo evidence for connectivity between the SC and the amygdala via the
      pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor
      imaging tractography revealed a streamlined path that passes dorsolaterally
      through the pulvinar before arcing rostrally to traverse above the temporal horn
      of the lateral ventricle and connect to the lateral amygdala. To obviate
      artifactual connectivity with crossing fibers of the stria terminalis, the stria
      was also dissected. The putative streamline between the SC and amygdala traverses
      above the temporal horn dorsal to the stria terminalis and is positioned medial
      to it in humans and lateral to it in monkeys. The topography of the streamline
      was examined in relation to lesion anatomy in five patients who had previously
      participated in behavioral experiments studying the processing of emotionally
      valenced visual stimuli. The pulvinar lesion interrupted the streamline in two
      patients who had exhibited contralesional processing deficits and spared the
      streamline in three patients who had no deficit. Although not definitive, this
      evidence supports the existence of a subcortical pathway linking the SC with the
      amygdala in primates. It also provides a necessary bridge between behavioral data
      obtained in future studies of neurological patients, and any forthcoming evidence
      from more invasive techniques, such as anatomical tracing studies and
      electrophysiological investigations only possible in nonhuman species. 

PMID- 26224781
TI  - Physical and Psychological Consequences of Left Cardiac Sympathetic Denervation
      in Long-QT Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia.
AB  - BACKGROUND: Left cardiac sympathetic denervation reduces risk in long-QT syndrome
      (LQTS) and catecholaminergic polymorphic ventricular tachycardia. Side effects
      and patient satisfaction have not been systematically analyzed in patients who
      underwent left cardiac sympathetic denervation. Aims of this study included
      documenting physical and psychological consequences and patient satisfaction
      after left cardiac sympathetic denervation in LQTS or catecholaminergic
      polymorphic ventricular tachycardia. METHODS AND RESULTS: Patients with LQTS
      (N=40) and catecholaminergic polymorphic ventricular tachycardia (N=7) underwent
      video-assisted thoracoscopic left cardiac sympathetic denervation, with a median
      follow-up of 29 months (range, 1-67 months). Clinical records were reviewed; 44
      patients completed a telephone survey. Of 47 patients (53%), 25 were
      preoperatively symptomatic (15 syncope, 7 near-drowning, and 3 resuscitated
      sudden death). Indications for left cardiac sympathetic denervation included beta
      blocker intolerance (15; 32%) or nonadherence (10; 21%) and disease factors (18;
      38%; catecholaminergic polymorphic ventricular tachycardia [6], near-drowning
      [2], exertional syncope [1], symptoms on therapy [2], LQT3 [1], QTc>520 ms [6]).
      Other indications were competitive sports participation (2), family history of
      sudden death (1), and other (1). Median QTc did not change among patients with
      LQTS (461+/-60 to 476+/-54 ms; P=0.49). Side effects were reported by 42 of 44
      (95%). Twenty-nine patients (66%) reported dryness on left side, 26 (59%) a
      Harlequin-type (unilateral) facial flush, 24 (55%) contralateral hyperhidrosis,
      17 (39%) differential hand temperatures, 5 (11%) permanent and 4 (9%) transient
      ptosis, 5 (11%) thermoregulation difficulties, 4 (9%) a sensation of left arm
      paresthesia, and 3 (7%) sympathetic flight/fright response loss. Majority of the
      patients were satisfied postoperatively: 38 (86%) were happy with the procedure,
      33 (75%) felt safer, 40 (91%) recommended the procedure to others, and 40 (91%)
      felt happy with their scar appearance. CONCLUSIONS: Despite significant morbidity
      resulting from left cardiac sympathetic denervation, patients with LQTS and CPVT
      have high levels of postoperative satisfaction.

PMID- 26224782
TI  - High-Density Genotypes of Inbred Mouse Strains: Improved Power and Precision of
      Association Mapping.
AB  - Human genome-wide association studies have identified thousands of loci
      associated with disease phenotypes. Genome-wide association studies also have
      become feasible using rodent models and these have some important advantages over
      human studies, including controlled environment, access to tissues for molecular
      profiling, reproducible genotypes, and a wide array of techniques for
      experimental validation. Association mapping with common mouse inbred strains
      generally requires 100 or more strains to achieve sufficient power and mapping
      resolution; in contrast, sample sizes for human studies typically are one or more
      orders of magnitude greater than this. To enable well-powered studies in mice, we
      have generated high-density genotypes for ~175 inbred strains of mice using the
      Mouse Diversity Array. These new data increase marker density by 1.9-fold, have
      reduced missing data rates, and provide more accurate identification of
      heterozygous regions compared with previous genotype data. We report the
      discovery of new loci from previously reported association mapping studies using
      the new genotype data. The data are freely available for download, and Web-based
      tools provide easy access for association mapping and viewing of the underlying
      intensity data for individual loci.

PMID- 26224783
TI  - Fingerprinting Soybean Germplasm and Its Utility in Genomic Research.
AB  - The United States Department of Agriculture, Soybean Germplasm Collection
      includes 18,480 domesticated soybean and 1168 wild soybean accessions introduced
      from 84 countries or developed in the United States. This collection was
      genotyped with the SoySNP50K BeadChip containing greater than 50K single
      nucleotide polymorphisms. Redundant accessions were identified in the collection,
      and distinct genetic backgrounds of soybean from different geographic origins
      were observed that could be a unique resource for soybean genetic improvement. We
      detected a dramatic reduction of genetic diversity based on linkage
      disequilibrium and haplotype structure analyses of the wild, landrace, and North
      American cultivar populations and identified candidate regions associated with
      domestication and selection imposed by North American breeding. We constructed
      the first soybean haplotype block maps in the wild, landrace, and North American
      cultivar populations and observed that most recombination events occurred in the
      regions between haplotype blocks. These haplotype maps are crucial for
      association mapping aimed at the identification of genes controlling traits of
      economic importance. A case-control association test delimited potential genomic
      regions along seven chromosomes that most likely contain genes controlling seed
      weight in domesticated soybean. The resulting dataset will facilitate germplasm
      utilization, identification of genes controlling important traits, and will
      accelerate the creation of soybean varieties with improved seed yield and
      quality. 

PMID- 26224784
TI  - The Genetics of Resistance to Morinda Fruit Toxin During the Postembryonic Stages
      in Drosophila sechellia.
AB  - Although a great deal has been learned regarding the genetic changes that give
      rise to adaptation in bacteria and yeast, an understanding of how new complex
      traits arise in multicellular organisms is far less complete. Many phytophagous
      insect species are ecological specialists that have adapted to utilize a single
      host plant. Drosophila sechellia is a specialist that utilizes the ripe fruit of
      Morinda citrifolia, which is toxic to its sibling species, D. simulans. Here we
      apply multiplexed shotgun genotyping and QTL analysis to examine the genetic
      basis of resistance to M. citrifolia fruit toxin in interspecific hybrids. We
      identify a locus of large effect on the third chromosome (QTL-IIIsima) in the D.
      simulans backcross that was not detected in previous analyses. We also identify a
      highly significant QTL of large effect on the X chromosome, QTL-Xsim. Additional
      smaller-effect loci were also identified in the D. simulans and D. sechellia
      backcrosses. We did not detect significant epistasis between loci. Instead, our
      analysis reveals large and smaller-effect loci that contribute to M. citrifolia
      resistance additively. The additive effect of each locus suggests that partial
      resistance to lower levels of M. citrifolia toxin could be passed through
      introgression from D. sechellia to D. simulans in nature. The identification of
      the major effect loci, QTL-IIIsima and QTL-Xsim, is an important step toward
      identifying the molecular basis of adaptation in a multicellular organism.

PMID- 26224786
TI  - The trans-sialidase, the major Trypanosoma cruzi virulence factor: Three decades
      of studies.
AB  - Chagas' disease is a potentially life-threatening disease caused by the protozoan
      parasite Trypanosoma cruzi. Since the description of Chagas'disease in 1909
      extensive research has identified important events in the disease in order to
      understand the biochemical mechanism that modulates T. cruzi-host cell
      interactions and the ability of the parasite to ensure its survival in the
      infected host. Exactly 30 years ago, we presented evidence for the first time of
      a trans-sialidase activity in T. cruzi (T. cruzi-TS). This enzyme transfers
      sialic acid from the host glycoconjugates to the terminal beta-galactopyranosyl
      residues of mucin-like molecules on the parasite's cell surface. Thenceforth,
      many articles have provided convincing data showing that T. cruzi-TS is able to
      govern relevant mechanisms involved in the parasite's survival in the mammalian
      host, such as invasion, escape from the phagolysosomal vacuole, differentiation,
      down-modulation of host immune responses, among others. The aim of this review is
      to cover the history of the discovery of T. cruzi-TS, as well as some well
      documented biological effects encompassed by this parasite's virulence factor, an
      enzyme with potential attributes to become a drug target against Chagas disease. 

PMID- 26224785
TI  - Novel Abetalipoproteinemia Missense Mutation Highlights the Importance of the N
      Terminal beta-Barrel in Microsomal Triglyceride Transfer Protein Function.
AB  - BACKGROUND: The use of microsomal triglyceride transfer protein (MTP) inhibitors
      is limited to severe hyperlipidemias because of associated hepatosteatosis and
      gastrointestinal adverse effects. Comprehensive knowledge about the structure
      function of MTP might help design new molecules that avoid steatosis.
      Characterization of mutations in MTP causing abetalipoproteinemia has revealed
      that the central alpha-helical and C-terminal beta-sheet domains are important
      for protein disulfide isomerase binding and lipid transfer activity. Our aim was
      to identify and characterize mutations in the N-terminal domain to understand its
      function. METHODS AND RESULTS: We identified a novel missense mutation (D169V) in
      a 4-month-old Turkish male child with severe signs of abetalipoproteinemia. To
      study the effect of this mutation on MTP function, we created mutants via site
      directed mutagenesis. Although D169V was expressed in the endoplasmic reticulum
      and interacted with apolipoprotein B (apoB) 17, it was unable to bind protein
      disulfide isomerase, transfer lipids, and support apoB secretion. Computational
      modeling suggested that D169 could form an internal salt bridge with K187 and
      K189. Mutagenesis of these lysines to leucines abolished protein disulfide
      isomerase heterodimerization, lipid transfer, and apoB secretion, without
      affecting apoB17 binding. Furthermore, mutants with preserved charges (D169E,
      K187R, and K189R) rescued these activities. CONCLUSIONS: D169V is detrimental
      because it disrupts an internal salt bridge leading to loss of protein disulfide
      isomerase binding and lipid transfer activities; however, it does not affect apoB
      binding. Thus, the N-terminal domain of MTP is also important for its lipid
      transfer activity.

PMID- 26224787
TI  - Coronary Artery Calcification Score as A Predictor of All-Cause Mortality and
      Cardiovascular Outcome in Peritoneal Dialysis Patients.
AB  - ? BACKGROUND: This study aimed to examine whether the coronary artery
      calcification score (CaCS) was associated with the prognosis of peritoneal
      dialysis (PD) patients. ? METHODS: Adult PD patients who were clinically stable
      for at least 2 months were recruited for this prospective, observational cohort
      study. Coronary artery calcification was assessed using multislice spiral
      computed tomography and was recorded according to the Agatston score. The
      endpoints including all-cause mortality, cardiovascular events, and
      cardiovascular mortality were assessed. Multivariate Cox regression was used to
      identify independent predictors of all-cause mortality, cardiovascular events
      (CVEs), and cardiovascular mortality. ? RESULTS: A total of 179 PD patients (86
      men) with a mean age of 63.5 +/- 14.8 years were recruited for this study.
      Coronary artery calcification scores ranging from 0 to 5,257 were stratified as
      follows: no (CaCS = 0, n = 54), low (0 < CaCS < 400, n = 72), and high (CaCS >=
      400, n = 53) calcification. The follow-up duration was 30.6 +/- 16.2 (24-63)
      months. Compared with the no calcification group, patients with a higher CaCS
      were older and had lower diastolic blood pressure, residual renal function, and
      serum albumin, and higher HbA1C and serum insulin. Multivariate Cox regression
      revealed that the CaCS was an independent predictor for all the 3 endpoints after
      adjustment in PD patients. ? CONCLUSIONS: CaCS was an independent predictor of
      all-cause mortality, cardiovascular events, and cardiovascular mortality in
      patients receiving peritoneal dialysis.

PMID- 26224788
TI  - Phosphate Removal by Peritoneal Dialysis: The Effect of Transporter Status and
      Peritoneal Dialysis Prescription.
AB  - ? BACKGROUND: Interventional trials failed to demonstrate that increasing urea
      clearance improved peritoneal dialysis (PD) patient survival. Hyperphosphatemia
      is a well-recognized predictor of cardiovascular and all-cause mortality in PD
      patients. Simplification of PD small solute clearance targets focuses away from
      larger solutes, including phosphate. In the US and UK, increasing use of
      automated peritoneal dialysis (APD) cyclers with shorter dwell times could also
      potentially reduce peritoneal phosphate removal compared to continuous ambulatory
      peritoneal dialysis (CAPD). ? METHODS: Total phosphate and peritoneal phosphate
      clearances were measured in a prospective observational cohort of 380 adult PD
      patients attending a tertiary university hospital between 1996 and 2013 for
      routine assessment of PD adequacy. ? RESULTS: Eighty-seven patients (22.9%) were
      hyperphosphatemic. Taking the mean 4-hour dialysate to plasma (D/P) ratio for
      phosphate, 193 (50.8%) were fast and fast-average transporters and 187 (49.2%)
      were slow and slow-average transporters (compared to 276 [72.6%] and 104 [27.4%],
      respectively, for peritoneal creatinine transporter status). Faster peritoneal
      phosphate transporter status was associated with over-hydration (odds ratio [OR]
      = 2.45 [1.43 - 4.20], p = 0.001). Whereas the 4-hour D/P creatinine and
      peritoneal weekly creatinine clearance did not differ between those who were
      hyperphosphatemic or not, the hyperphosphatemic patients had lower 4-hour D/P
      phosphate and lower peritoneal weekly phosphate clearance (p = 0.019, and p =
      0.06 respectively). We found greater peritoneal phosphate clearance for patients
      choosing CAPD compared to APD, irrespective of the peritoneal phosphate
      transporter status. ? CONCLUSION: Peritoneal creatinine transporter status and
      creatinine clearance cannot be used as surrogate markers of peritoneal phosphate
      transport and clearance. Hyperphosphatemia was more common in PD patients with
      slower peritoneal transporter status and lower peritoneal phosphate clearance.
      Greater peritoneal phosphate clearance was achieved with CAPD prescriptions.
      Slower peritoneal transporters should be advised to choose CAPD to improve serum
      phosphate control.

PMID- 26224789
TI  - Influence of Different Payment Schemes on the Clinical Outcome in Peritoneal
      Dialysis Patients.
AB  - ? BACKGROUND: Cost is always a big issue for dialysis patients. In the present
      study, we analyzed the effect of different payment schemes on dialysis adequacy
      and clinical outcome in our peritoneal dialysis program. ? METHODS: This is a
      single-center cohort study. A total of 175 patients who began dialysis from
      January 2006 to December 2007 were included. Baseline data, including volume
      status, dietary intake and nutrition status, dialysis adequacy, and sodium
      removal were collected at 6 months after peritoneal dialysis. Based on the
      different payment schemes, the patients were divided into 2 groups, higher
      payment group (GHP, 130 cases, with more than 85% reimbursement), and lower
      payment group (GLP, 45 cases, with less than 50% payment or totally self-paid).
      Patients were followed up until dropout or until December 31, 2013. ? RESULTS: At
      baseline, patients in the 2 groups had nearly the same residual renal function.
      But the GLP group patients dialyzed at a lower dose (4,516.91 +/- 1,768.20 mL vs
      6,058.17 +/- 2,013.43 mL, p < 0.001). They had lower creatinine clearance (51.64
      +/- 24.23 L/w vs 70.54 +/- 30.27 L/w, p < 0.001), sodium removal (2.23 +/- 1.29 g
      vs 2.77 +/- 1.29 g, p = 0.027), and fluid removal (970.33 +/- 545.97 mL vs
      1,146.66 +/- 460.93 mL, p = 0.038). Normalized by height (in meters), the GLP
      group patients still had a lower normalized dialysis dose (2,890.61 +/- 1084.44
      mL/m vs 3,761.34 +/- 1,237.10 mL/m, p < 0.001). Baseline nutritional and dietary
      parameters were comparable except that a lower daily protein intake (42.73 +/-
      10.99 g vs 47.26 +/- 14.30 g, p = 0.032) and higher serum urea level (23.43 +/-
      6.88 mmol/L vs 19.84 +/- 5.92 mmol/L, p < 0.001) were presented in the GLP group.
      There was no difference in volume status. During the follow-up, Kaplan-Meier
      analysis showed that there was no significant difference in patient survival and
      technique survival. In multivariate Cox regression analysis, after adjusting for
      related factors, payment was again not a strong predictor of survival in the
      study population. ? CONCLUSION: Our study found that GLP group patients were
      adherent to lifestyle modification with lower dialysis doses, and they also had
      nearly the same long-term clinical outcome as the GHP group patients. Thus, lower
      dialysis doses combined with controlled dietary intake may be an effective
      approach to solve the dialysis problem for the low socio-economic status (SES)
      population.

PMID- 26224790
TI  - The Effect of Exit-Site Antibacterial Honey Versus Nasal Mupirocin Prophylaxis on
      the Microbiology and Outcomes of Peritoneal Dialysis-Associated Peritonitis and
      Exit-Site Infections: A Sub-Study of the Honeypot Trial.
AB  - ? BACKGROUND: The HONEYPOT study recently reported that daily exit-site
      application of antibacterial honey was not superior to nasal mupirocin
      prophylaxis for preventing overall peritoneal dialysis (PD)-related infection.
      This paper reports a secondary outcome analysis of the HONEYPOT study with
      respect to exit-site infection (ESI) and peritonitis microbiology, infectious
      hospitalization and technique failure. ? METHODS: A total of 371 PD patients were
      randomized to daily exit-site application of antibacterial honey plus usual exit
      site care (N = 186) or intranasal mupirocin prophylaxis (in nasal Staphylococcus
      aureus carriers only) plus usual exit-site care (control, N = 185). Groups were
      compared on rates of organism-specific ESI and peritonitis, peritonitis- and
      infection-associated hospitalization, and technique failure (PD withdrawal). ?
      RESULTS: The mean peritonitis rates in the honey and control groups were 0.41
      (95% confidence interval [CI] 0.32 - 0.50) and 0.41 (95% CI 0.33 - 0.49) episodes
      per patient-year, respectively (incidence rate ratio [IRR] 1.01, 95% CI 0.75 -
      1.35). When specific causative organisms were examined, no differences were
      observed between the groups for gram-positive (IRR 0.99, 95% CI 0.66 - 1.49),
      gram-negative (IRR 0.71, 95% CI 0.39 - 1.29), culture-negative (IRR 2.01, 95% CI
      0.91 - 4.42), or polymicrobial peritonitis (IRR 1.08, 95% CI 0.36 - 3.20). Exit
      site infection rates were 0.37 (95% CI 0.28 - 0.45) and 0.33 (95% CI 0.26 - 0.40)
      episodes per patient-year for the honey and control groups, respectively (IRR
      1.12, 95% CI 0.81 - 1.53). No significant differences were observed between the
      groups for gram-positive (IRR 1.10, 95% CI 0.70 - 1.72), gram-negative (IRR:
      0.85, 95% CI 0.46 - 1.58), culture-negative (IRR 1.88, 95% CI 0.67 - 5.29), or
      polymicrobial ESI (IRR 1.00, 95% CI 0.40 - 2.54). Times to first peritonitis
      associated and first infection-associated hospitalization were similar in the
      honey and control groups. The rates of technique failure (PD withdrawal) due to
      PD-related infection were not significantly different between the groups. ?
      CONCLUSION: Compared with standard nasal mupirocin prophylaxis, daily topical
      exit-site application of antibacterial honey resulted in comparable rates of
      organism-specific peritonitis and ESI, infection-associated hospitalization, and
      infection-associated technique failure in PD patients.

PMID- 26224791
TI  - Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis
      Associated Peritonitis.
AB  - ? BACKGROUND: As an immune system regulator, vitamin D is commonly deficient
      among patients on peritoneal dialysis (PD), which may contribute to their
      impaired immune function and increased risk for PD-related peritonitis. In this
      study, we aimed to investigate whether vitamin D deficiency could predict the
      risk of peritonitis in a prospective cohort of patients on PD. ? METHODS: We
      collected 346 prevalent and incident PD patients from 2 hospitals. Baseline
      demographic data and clinical characteristics were recorded. Serum 25
      hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The
      mean doses of oral active vitamin D used during the study period were also
      recorded. The outcome was the occurrence of peritonitis. ? RESULTS: The mean age
      of patients and duration of PD were 58.95 +/- 13.67 years and 28.45 (15.04 -
      53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 - 21.16)
      nmol/L, which was closely associated with diabetic status, longer PD duration,
      malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence
      of peritonitis independently of active vitamin D supplementation with a hazard
      ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 - 0.98) after adjusting for
      recognized confounders (age, gender, dialysis duration, diabetes, albumin,
      residual renal function, and history of peritonitis). Compared to the low
      tertile, middle and high 25(OH)D level tertiles were associated with a decreased
      risk for peritonitis with HRs of 0.54 (95% CI 0.31 - 0.94) and 0.39 (95% CI 0.20 
      0.75), respectively. ? CONCLUSIONS: Vitamin D deficiency evaluated by serum
      25(OH)D rather than active vitamin D supplementation is closely associated with a
      higher risk of peritonitis.

PMID- 26224792
TI  - Clinical Risk Stratification for Primary Prevention Implantable Cardioverter
      Defibrillators.
AB  - BACKGROUND: A conceptualized model may be useful for understanding risk
      stratification of primary prevention implantable cardioverter defibrillators
      considering the competing risks of appropriate implantable cardioverter
      defibrillator shock versus mortality. METHODS AND RESULTS: In a prospective,
      multicenter, population-based cohort with left ventricular ejection fraction
      <=35% referred for primary prevention implantable cardioverter defibrillator, we
      developed dual risk stratification models to determine the competing risks of
      appropriate defibrillator shock versus mortality using a Fine-Gray
      subdistribution hazard model. Among 7020 patients referred, 3445 underwent
      defibrillator implant (79.7% men, median, 66 years [25th, 75th: 58-73]). During
      5918 person-years of follow-up, appropriate shock occurred in 204 patients (3.6
      shocks/100 person-years) and 292 died (4.9 deaths/100 person-years). Competing
      risk predictors of appropriate shock included nonsustained ventricular
      tachycardia, atrial fibrillation, serum creatinine concentration, digoxin or
      amiodarone use, and QRS duration near 130-ms peak. One-year cumulative incidence
      of appropriate shock was 0.9% in the lowest risk category, and 1.7%, 2.5%, 4.9%,
      and 9.3% in low, intermediate, high, and highest risk groups, respectively.
      Hazard ratios for appropriate shock ranged from 4.04 to 7.79 in the highest 3
      deciles (all P<=0.001 versus lowest risk). Cumulative incidence of 1-year death
      was 0.6%, 1.9%, 3.3%, 6.2%, and 17.7% in lowest, low, intermediate, high, and
      highest risk groups, respectively. Mortality hazard ratios ranged from 11.48 to
      36.22 in the highest 3 deciles (all P<0.001 versus lowest risk). CONCLUSIONS:
      Simultaneous estimation of risks of appropriate shock and mortality can be
      performed using clinical variables, providing a potential framework for
      identification of patients who are unlikely to benefit from prophylactic
      implantable cardioverter defibrillator.

PMID- 26224795
TI  - Bromodomain-Containing Protein 4: The Epigenetic Origin of Pulmonary Arterial
      Hypertension.
AB  - RATIONALE: Pulmonary arterial hypertension (PAH) is a vasculopathy characterized
      by enhanced pulmonary artery (PA) smooth muscle cell (PASMC) proliferation and
      suppressed apoptosis. Decreased expression of microRNA-204 has been associated to
      this phenotype. By a still elusive mechanism, microRNA-204 downregulation
      promotes the expression of oncogenes, including nuclear factor of activated T
      cells, B-cell lymphoma 2, and Survivin. In cancer, increased expression of the
      epigenetic reader bromodomain-containing protein 4 (BRD4) sustains cell survival
      and proliferation. Interestingly, BRD4 is a predicted target of microRNA-204 and
      has binding sites on the nuclear factor of activated T cells promoter region.
      OBJECTIVE: To investigate the role of BRD4 in PAH pathogenesis. METHODS AND
      RESULTS: BRD4 is upregulated in lungs, distal PAs, and PASMCs of patients with
      PAH compared with controls. With mechanistic in vitro experiments, we
      demonstrated that BRD4 expression in PAH is microRNA-204 dependent. We further
      studied the molecular downstream targets of BRD4 by inhibiting its activity in
      PAH-PASMCs using a clinically available inhibitor JQ1. JQ1 treatment in PAH
      PASMCs increased p21 expression, thus triggering cell cycle arrest. Furthermore,
      BRD4 inhibition, by JQ1 or siBRD4, decreased the expression of 3 major oncogenes,
      which are overexpressed in PAH: nuclear factor of activated T cells, B-cell
      lymphoma 2, and Survivin. Blocking this oncogenic signature led to decreased PAH
      PASMC proliferation and increased apoptosis in a BRD4-dependent manner. Indeed,
      pharmacological JQ1 or molecular (siRNA) inhibition of BRD4 reversed this
      pathological phenotype in addition to restoring mitochondrial membrane potential
      and to increasing cells spare respiratory capacity. Moreover, BRD4 inhibition in
      vivo reversed established PAH in the Sugen/hypoxia rat model. CONCLUSIONS: BRD4
      plays a key role in the pathological phenotype in PAH, which could offer new
      therapeutic perspectives for patients with PAH.

PMID- 26224794
TI  - Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation.
AB  - RATIONALE: In the working heart, coronary blood flow is linked to the production
      of metabolites, which modulate tone of smooth muscle in a redox-dependent manner.
      Voltage-gated potassium channels (Kv), which play a role in controlling membrane
      potential in vascular smooth muscle, have certain members that are redox
      sensitive. OBJECTIVE: To determine the role of redox-sensitive Kv1.5 channels in
      coronary metabolic flow regulation. METHODS AND RESULTS: In mice (wild-type [WT],
      Kv1.5 null [Kv1.5(-/-)], and Kv1.5(-/-) and WT with inducible, smooth muscle
      specific expression of Kv1.5 channels), we measured mean arterial pressure,
      myocardial blood flow, myocardial tissue oxygen tension, and ejection fraction
      before and after inducing cardiac stress with norepinephrine. Cardiac work was
      estimated as the product of mean arterial pressure and heart rate. Isolated
      arteries were studied to establish whether genetic alterations modified vascular
      reactivity. Despite higher levels of cardiac work in the Kv1.5(-/-) mice (versus
      WT mice at baseline and all doses of norepinephrine), myocardial blood flow was
      lower in Kv1.5(-/-) mice than in WT mice. At high levels of cardiac work, tissue
      oxygen tension dropped significantly along with ejection fraction. Expression of
      Kv1.5 channels in smooth muscle in the null background rescued this phenotype of
      impaired metabolic dilation. In isolated vessels from Kv1.5(-/-) mice, relaxation
      to H2O2 was impaired, but responses to adenosine and acetylcholine were normal
      compared with those from WT mice. CONCLUSIONS: Kv1.5 channels in vascular smooth
      muscle play a critical role in coupling myocardial blood flow to cardiac
      metabolism. Absence of these channels disassociates metabolism from flow,
      resulting in cardiac pump dysfunction and tissue hypoxia.

PMID- 26224796
TI  - Anal Cancer Incidence in the United States, 1977-2011: Distinct Patterns by
      Histology and Behavior.
AB  - BACKGROUND: Although anal squamous cell carcinoma (SCC) and adenocarcinoma (ADC)
      are generally combined in cancer surveillance, their etiologies likely differ.
      Here, we describe demographic characteristics and trends in incidence rates (IR)
      of anal cancer by histology (SCC, ADC) and behavior (invasive, in situ) in the
      United States. METHODS: With data from the Surveillance, Epidemiology, and End
      Results (SEER) Program, we estimated age-adjusted anal cancer IRs across
      behavior/histology by demographic and tumor characteristics for 2000-2011. Trends
      in IRs and annual percent changes during 1977-2011 were also estimated and
      compared with rectal cancer. RESULTS: Women had higher rates of SCC [rate ratio
      (RR), 1.45; 95% confidence interval (CI), 1.40-1.50] and lower rates of ADC (RR,
      0.68; 95% CI, 0.62-0.74) and squamous carcinoma in situ (CIS; RR, 0.36; 95% CI,
      0.34-0.38) than men. Blacks had lower rates of SCC (RR, 0.82; 95% CI, 0.77-0.87)
      and CIS (RR, 0.90; 95% CI, 0.83-0.98) than non-Hispanic whites, but higher rates
      of ADC (RR, 1.48; 95% CI, 1.29-1.70). Anal cancer IRs were higher in men and
      blacks aged <40 years. During 1992-2011, SCC IRs increased 2.9%/year, ADC IRs
      declined nonsignificantly, and CIS IRs increased 14.2%/year. SCC and ADC IR
      patterns and trends were similar across anal and rectal cancers. CONCLUSIONS:
      Rates of anal SCC and CIS have increased strongly over time, in contrast to rates
      of anal ADC, similar to trends observed for rectal SCC and ADC. IMPACT: Anal SCC
      and ADC likely have different etiologies, but may have similar etiologies to
      rectal SCC and ADC, respectively. Strong increases in CIS IRs over time may
      reflect anal cancer screening patterns.

PMID- 26224798
TI  - Circulating C-Reactive Protein and Breast Cancer Risk-Systematic Literature
      Review and Meta-analysis of Prospective Cohort Studies.
AB  - We conducted a systematic literature review to explore the association between
      circulating C-reactive protein (CRP), a low-grade inflammation biomarker, and
      breast cancer risk. Relevant prospective studies in women were identified in
      PubMed and Web of Science until February 2015. Random-effects dose-response meta
      analysis was conducted, overall and in postmenopausal women. Twelve out of 15
      studies identified were included in the meta-analysis on any breast cancers
      (3,522 cases; 69,610 women) and nine on postmenopausal breast cancer (2,516
      cases; 36,847 women). For each doubling of CRP concentration, a 7% [95%
      confidence interval (CI), 2%-12%] and 6% (95% CI, 1%-11%) increased risk was
      observed (I(2) = 47% and 32%; Pheterogeneity = 0.04 and 0.17), respectively. The
      association was linear over most of the range of CRP concentrations. Positive
      associations remained in the studies that examined the exclusion of early years
      of follow-up. Associations were attenuated in studies adjusted for lifestyle
      factors, which partly explained the significant heterogeneity between studies in
      the overall analysis. On average, the associations in studies adjusted or not
      adjusted for body mass index were similar. Low-grade inflammation may have a role
      in breast cancer development. Additional prospective studies are needed to better
      understand confounding and effect modification from lifestyle factors.

PMID- 26224797
TI  - Intake of Meat Mutagens and Risk of Prostate Cancer in a Cohort of U.S. Health
      Professionals.
AB  - BACKGROUND: Evidence relating heterocyclic aromatic amines (HCA), associated with
      high-temperature cooking methods, to prostate cancer risk is inconsistent.
      METHODS: In a large U.S. cohort study, intakes of 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline
      (DiMeIQx) and a meat-derived mutagenicity (MDM) index were assessed using a
      cooking method questionnaire administered in 1996. Until 2010, 2,770 prostate
      cancer cases were observed among 26,030 participants. RESULTS: Intake of PhIP
      from red meat was statistically significantly associated with total prostate
      cancer risk (top vs. bottom quintile HR, 1.18; 95% confidence intervals; CI, 1.03
      1.35), but not other HCAs (MeIQx, 1.12; 0.98-1.27, PhIP from white meat, 1.08;
      0.95-1.22, DiMeIQx, 1.09; 0.97-1.21) or MDM (1.13; 1.00-1.28). For high-grade
      (Gleason sum 7 with pattern 4+3 and Gleason sum 8-10, n = 483 cases) and advanced
      cancers (n = 281), we only observed positive associations for PhIP from red meat
      (top vs. bottom quintile: high grade: HR, 1.44; 95% CI, 1.04-1.98, Ptrend = 0.03;
      advanced: HR, 1.50; 95% CI, 0.99-2.26; Ptrend = 0.12), but associations for
      advanced cancers did not reach statistical significance. Observed associations
      remained similar after adjustment for total, unprocessed, or processed red meat
      intake. CONCLUSION: Observed positive associations between PhIP intake from red
      meat and prostate cancer, particularly high-grade and possibly also advanced
      prostate cancer, need to be confirmed in other studies. IMPACT: Results do not
      provide strong evidence that HCAs increase risk of prostate cancers.

PMID- 26224799
TI  - No Association Between Vitamin D Intake, VDR Polymorphisms, and Colorectal Cancer
      in a Population-Based Case-Control Study.
AB  - BACKGROUND: Epidemiologic evidence indicates that greater intakes of vitamin D
      may decrease the risk of colorectal cancer. Variants in the vitamin D receptor
      (VDR) gene have the potential to modify associations between vitamin D intake and
      colorectal cancer. METHODS: Associations between intakes of vitamin D and
      colorectal cancer were studied in a large case-control study conducted in central
      and northeastern Pennsylvania including 1,012 cases with histologically confirmed
      colorectal cancer and 1,080 population-based controls. Associations between 35
      tagSNPs encompassing the VDR gene and risk for colorectal cancer as well as gene
      diet associations were also assessed among a subset of the population (770
      controls, 710 cases). RESULTS: No significant trends were observed between
      vitamin D intake and colorectal cancer risk. After adjustment for multiple
      comparisons, none of the SNPs or haplotypes within the VDR gene were associated
      with colorectal cancer. There were also no interactions between dietary factors
      and variants in the entire VDR gene. CONCLUSIONS: Overall, results from this
      study suggest that vitamin D intake and variants in the VDR gene have little
      effect on risk for colorectal cancer. IMPACT: Increasing vitamin D intake from
      the diet may not result in decreasing the incidence of colorectal cancer.

PMID- 26224800
TI  - Half-of-the-Sites Reactivity of the Castor Delta9-18:0-Acyl Carrier Protein
      Desaturase.
AB  - Fatty acid desaturases regulate the unsaturation status of cellular lipids. They
      comprise two distinct evolutionary lineages, a soluble class found in the
      plastids of higher plants and an integral membrane class found in plants, yeast
      (Saccharomyces cerevisiae), animals, and bacteria. Both classes exhibit a dimeric
      quaternary structure. Here, we test the functional significance of dimeric
      organization of the soluble castor Delta9-18:0-acyl carrier protein desaturase,
      specifically, the hypothesis that the enzyme uses an alternating subunit half-of
      the-sites reactivity mechanism whereby substrate binding to one subunit is
      coordinated with product release from the other subunit. Using a fluorescence
      resonance energy transfer assay, we demonstrated that dimers stably associate at
      concentrations typical of desaturase assays. An active site mutant T104K/S202E,
      designed to occlude the substrate binding cavity, was expressed, purified, and
      its properties validated by x-ray crystallography, size exclusion chromatography,
      and activity assay. Heterodimers comprising distinctly tagged wild-type and
      inactive mutant subunits were purified at 1:1 stoichiometry. Despite having only
      one-half the number of active sites, purified heterodimers exhibit equivalent
      activity to wild-type homodimers, consistent with half-of-the-sites reactivity.
      However, because multiple rounds of turnover were observed, we conclude that
      substrate binding to one subunit is not required to facilitate product release
      from the second subunit. The observed half-of-the-sites reactivity could
      potentially buffer desaturase activity from oxidative inactivation. That soluble
      desaturases require only one active subunit per dimer for full activity
      represents a mechanistic difference from the membrane class of desaturases such
      as the Delta9-acyl-CoA, Ole1p, from yeast, which requires two catalytically
      competent subunits for activity. 

PMID- 26224801
TI  - Populus euphratica APYRASE2 Enhances Cold Tolerance by Modulating Vesicular
      Trafficking and Extracellular ATP in Arabidopsis Plants.
AB  - Apyrase and extracellular ATP play crucial roles in mediating plant growth and
      defense responses. In the cold-tolerant poplar, Populus euphratica, low
      temperatures up-regulate APYRASE2 (PeAPY2) expression in callus cells. We
      investigated the biochemical characteristics of PeAPY2 and its role in cold
      tolerance. We found that PeAPY2 predominantly localized to the plasma membrane,
      but punctate signals also appeared in the endoplasmic reticulum and Golgi
      apparatus. PeAPY2 exhibited broad substrate specificity, but it most efficiently
      hydrolyzed purine nucleotides, particularly ATP. PeAPY2 preferred Mg(2+) as a
      cofactor, and it was insensitive to various, specific ATPase inhibitors. When
      PeAPY2 was ectopically expressed in Arabidopsis (Arabidopsis thaliana), cold
      tolerance was enhanced, based on root growth measurements and survival rates.
      Moreover, under cold stress, PeAPY2-transgenic plants maintained plasma membrane
      integrity and showed reduced cold-elicited electrolyte leakage compared with wild
      type plants. These responses probably resulted from efficient plasma membrane
      repair via vesicular trafficking. Indeed, transgenic plants showed accelerated
      endocytosis and exocytosis during cold stress and recovery. We found that low
      doses of extracellular ATP accelerated vesicular trafficking, but high
      extracellular ATP inhibited trafficking and reduced cell viability. Cold stress
      caused significant increases in root medium extracellular ATP. However, under
      these conditions, PeAPY2-transgenic lines showed greater control of extracellular
      ATP levels than wild-type plants. We conclude that Arabidopsis plants that
      overexpressed PeAPY2 could increase membrane repair by accelerating vesicular
      trafficking and hydrolyzing extracellular ATP to avoid excessive, cold-elicited
      ATP accumulation in the root medium and, thus, reduced ATP-induced inhibition of
      vesicular trafficking. 

PMID- 26224803
TI  - Mutations in the Prokaryotic Pathway Rescue the fatty acid biosynthesis1 Mutant
      in the Cold.
AB  - The Arabidopsis (Arabidopsis thaliana) fatty acid biosynthesis1 (fab1) mutant has
      increased levels of the saturated fatty acid 16:0 due to decreased activity of 3
      ketoacyl-acyl carrier protein (ACP) synthase II. In fab1 leaves,
      phosphatidylglycerol, the major chloroplast phospholipid, contains up to 45% high
      melting-point molecular species (molecules that contain only 16:0, 16:1-trans,
      and 18:0), a trait associated with chilling-sensitive plants, compared with less
      than 10% in wild-type Arabidopsis. Although they do not exhibit typical chilling
      sensitivity, when exposed to low temperatures (2 degrees C-6 degrees C) for long
      periods, fab1 plants do suffer collapse of photosynthesis, degradation of
      chloroplasts, and eventually death. A screen for suppressors of this low
      temperature phenotype has identified 11 lines, some of which contain additional
      alterations in leaf-lipid composition relative to fab1. Here, we report the
      identification of two suppressor mutations, one in act1, which encodes the
      chloroplast acyl-ACP:glycerol-3-phosphate acyltransferase, and one in lpat1,
      which encodes the chloroplast acyl-ACP:lysophosphatidic acid acyltransferase.
      These enzymes catalyze the first two steps of the prokaryotic pathway for
      glycerolipid synthesis, so we investigated whether other mutations in this
      pathway would rescue the fab1 phenotype. Both the gly1 mutation, which reduces
      glycerol-3-phosphate supply to the prokaryotic pathway, and fad6, which is
      deficient in the chloroplast 16:1/18:1 fatty acyl desaturase, were discovered to
      be suppressors. Analyses of leaf-lipid compositions revealed that mutations at
      all four of the suppressor loci result in reductions in the proportion of high
      melting-point molecular species of phosphatidylglycerol relative to fab1. We
      conclude that these reductions are likely the basis for the suppressor
      phenotypes. 

PMID- 26224802
TI  - Constitutive Expression of Rice MicroRNA528 Alters Plant Development and Enhances
      Tolerance to Salinity Stress and Nitrogen Starvation in Creeping Bentgrass.
AB  - MicroRNA528 (miR528) is a conserved monocot-specific small RNA that has the
      potential of mediating multiple stress responses. So far, however, experimental
      functional studies of miR528 are lacking. Here, we report that overexpression of
      a rice (Oryza sativa) miR528 (Osa-miR528) in transgenic creeping bentgrass
      (Agrostis stolonifera) alters plant development and improves plant salt stress
      and nitrogen (N) deficiency tolerance. Morphologically, miR528-overexpressing
      transgenic plants display shortened internodes, increased tiller number, and
      upright growth. Improved salt stress resistance is associated with increased
      water retention, cell membrane integrity, chlorophyll content, capacity for
      maintaining potassium homeostasis, CATALASE activity, and reduced ASCORBIC ACID
      OXIDASE (AAO) activity; while enhanced tolerance to N deficiency is associated
      with increased biomass, total N accumulation and chlorophyll synthesis, nitrite
      reductase activity, and reduced AAO activity. In addition, AsAAO and COPPER ION
      BINDING PROTEIN1 are identified as two putative targets of miR528 in creeping
      bentgrass. Both of them respond to salinity and N starvation and are
      significantly down-regulated in miR528-overexpressing transgenics. Our data
      establish a key role that miR528 plays in modulating plant growth and development
      and in the plant response to salinity and N deficiency and indicate the potential
      of manipulating miR528 in improving plant abiotic stress resistance. 

PMID- 26224804
TI  - A Single Amino Acid Substitution in an ORANGE Protein Promotes Carotenoid
      Overaccumulation in Arabidopsis.
AB  - Carotenoids are crucial for plant growth and human health. The finding of ORANGE
      (OR) protein as a pivotal regulator of carotenogenesis offers a unique
      opportunity to comprehensively understand the regulatory mechanisms of carotenoid
      accumulation and develop crops with enhanced nutritional quality. Here, we
      demonstrated that alteration of a single amino acid in a wild-type OR greatly
      enhanced its ability to promote carotenoid accumulation. Whereas overexpression
      of OR from Arabidopsis (Arabidopsis thaliana; AtOR) or from the agronomically
      important crop sorghum (Sorghum bicolor; SbOR) increased carotenoid levels up to
      2-fold, expression of AtOR(His) (R90H) or SbOR(His) (R104H) variants dramatically
      enhanced carotenoid accumulation by up to 7-fold in the Arabidopsis calli.
      Moreover, we found that AtOR(Ala) (R90A) functioned similarly to AtOR(His) to
      promote carotenoid overproduction. Neither AtOR nor AtOR(His) greatly affected
      carotenogenic gene expression. AtOR(His) exhibited similar interactions with
      phytoene synthase (PSY) as AtOR in posttranscriptionally regulating PSY protein
      abundance. AtOR(His) triggered biogenesis of membranous chromoplasts in the
      Arabidopsis calli, which shared structures similar to chromoplasts found in the
      curd of the orange cauliflower (Brassica oleracea) mutant. By contrast, AtOR did
      not cause plastid-type changes in comparison with the controls, but produced
      plastids containing larger and electron-dense plastoglobuli. The unique ability
      of AtOR(His) in mediating chromoplast biogenesis is responsible for its induced
      carotenoid overproduction. Our study demonstrates OR(His/Ala) as powerful tools
      for carotenoid enrichment in plants, and provides insights into the mechanisms
      underlying OR(His)-regulated carotenoid accumulation. 

PMID- 26224805
TI  - A Revolution in Plant Metabolism: Genome-Enabled Pathway Discovery.
AB  - Genome-enabled discoveries are the hallmark of 21st century biology, including
      major discoveries in the biosynthesis and regulation of plant metabolic pathways.
      Access to next generation sequencing technologies has enabled research on the
      biosynthesis of diverse plant metabolites, especially secondary metabolites,
      resulting in a broader understanding of not only the structural and regulatory
      genes involved in metabolite biosynthesis but also in the evolution of chemical
      diversity in the plant kingdom. Several paradigms that govern secondary
      metabolism have emerged, including that (1) gene family expansion and
      diversification contribute to the chemical diversity found in the plant kingdom,
      (2) genes encoding biochemical pathway components are frequently
      transcriptionally coregulated, and (3) physical clustering of nonhomologous genes
      that encode components of secondary metabolic pathways can occur. With an
      increasing knowledge base that is coupled with user-friendly and inexpensive
      technologies, biochemists are poised to accelerate the annotation of biochemical
      pathways relevant to human health, agriculture, and the environment. 

PMID- 26224807
TI  - Nontraditional Markers of Cardiovascular Disease Risk Can Improve the 2013
      American College of Cardiology/American Heart Association Prevention Guidelines:
      Insights From the Multi-Ethnic Study of Atherosclerosis Investigation.

PMID- 26224808
TI  - Utility of Nontraditional Risk Markers in Individuals Ineligible for Statin
      Therapy According to the 2013 American College of Cardiology/American Heart
      Association Cholesterol Guidelines.
AB  - BACKGROUND: In the general population, the majority of cardiovascular events
      occur in people at the low to moderate end of population risk distribution. The
      2013 American College of Cardiology/American Heart Association guideline on the
      treatment of blood cholesterol recommends consideration of statin therapy for
      adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD)
      risk >=7.5% based on traditional risk factors. Whether use of nontraditional risk
      markers can improve risk assessment in those below this threshold for statin
      therapy is unclear. METHODS AND RESULTS: Using data from the Multi-Ethnic Study
      of Atherosclerosis (MESA), a population sample free of clinical CVD at baseline,
      we calibrated the Pooled Cohort Equations (cPCE). ASCVD was defined as myocardial
      infarction, coronary heart disease death, or fatal or nonfatal stroke. Adults
      with an initial cPCE <7.5% and elevated levels of additional risk markers
      (abnormal test) whose new calculated risk was >=7.5% were considered statin
      eligible: low-density lipoprotein cholesterol >=160 mg/dL; family history of
      ASCVD; high-sensitivity C-reactive protein >=2 mg/dL; coronary artery calcium
      score >=300 Agatston units or >=75th percentile for age, sex, and ethnicity; and
      ankle-brachial index <0.9. We compared the absolute and relative ASCVD risks
      among those with versus without elevated posttest estimated risk. We calculated
      the number needed to screen to identify 1 person with abnormal test for each risk
      marker, defined as the number of participants with baseline cPCE risk <7.5%
      divided by the number with an abnormal test reclassified as statin eligible. Of
      5185 participants not taking statins with complete data (age, 45-84 years), 4185
      had a cPCE risk <7.5%. During 10 years of follow-up, 57% of the ASCVD events (183
      of 320) occurred among adults with a cPCE risk <7.5%. When people with diabetes
      mellitus were excluded, the coronary artery calcium criterion reclassified 6.8%
      upward, with an event rate of 13.3%, absolute risk of 10%, relative risk of 4.0
      (95% confidence interval [CI], 2.8-5.7), and number needed to screen of 14.7. The
      corresponding numbers for family history of ASCVD were 4.6%, 15.1%, 12%, 4.3 (95%
      CI, 3.0-6.4), and 21.8; for high-sensitivity C-reactive protein criteria, 2.6%,
      10%, 6%, 2.6 (95% CI, 1.4-4.8), and 39.2; for ankle-brachial index criteria,
      0.6%, 9%, 5%, 2.3 (95% CI, 0.6-8.6), and 176.5; and for low-density lipoprotein
      cholesterol criteria, 0.5%, 5%, 1%, 1.2 (95% CI, 0.2-8.4), and 193.3,
      respectively. Of the 3882 with <7.5% cPCE risk, 431 (11.1%) were reclassified to
      >=7.5% (statin eligible) by at least 1 of the additional risk marker criteria.
      CONCLUSIONS: In this generally low-risk population sample, a large proportion of
      ASCVD events occurred among adults with a 10-year cPCE risk <7.5%. We found that
      the coronary artery calcium score, high-sensitivity C-reactive protein, family
      history of ASCVD, and ankle-brachial index recommendations by the American
      College of Cardiology/American Heart Association cholesterol guidelines (Class
      IIB) identify small subgroups of asymptomatic population with a 10-year cPCE risk
      <7.5% but with observed ASCVD event rates >7.5% who may warrant statin therapy
      considerations.

PMID- 26224809
TI  - A Not-So-Little Role for Lipoprotein(a) in the Development of Calcific Aortic
      Valve Disease.

PMID- 26224810
TI  - Autotaxin Derived From Lipoprotein(a) and Valve Interstitial Cells Promotes
      Inflammation and Mineralization of the Aortic Valve.
AB  - BACKGROUND: Mendelian randomization studies have highlighted that lipoprotein(a)
      [Lp(a)] was associated with calcific aortic valve disease (CAVD). Lp(a)
      transports oxidized phospholipids with a high content in lysophosphatidylcholine.
      Autotaxin (ATX) transforms lysophosphatidylcholine into lysophosphatidic acid. We
      hypothesized that ATX-lysophosphatidic acid could promote
      inflammation/mineralization of the aortic valve. METHODS AND RESULTS: We have
      documented the expression of ATX in control and mineralized aortic valves. By
      using different approaches, we have also investigated the role of ATX
      lysophosphatidic acid in the mineralization of isolated valve interstitial cells
      and in a mouse model of CAVD. Enzyme-specific ATX activity was elevated by 60% in
      mineralized aortic valves in comparison with control valves. Immunohistochemistry
      studies showed a high level of ATX in mineralized aortic valves, which
      colocalized with oxidized phospholipids and apolipoprotein(a). We detected a high
      level of ATX activity in the Lp(a) fraction in circulation. Interaction between
      ATX and Lp(a) was confirmed by in situ proximity ligation assay. Moreover, we
      documented that valve interstitial cells also expressed ATX in CAVD. We showed
      that ATX-lysophosphatidic acid promotes the mineralization of the aortic valve
      through a nuclear factor kappaB/interleukin 6/bone morphogenetic protein pathway.
      In LDLR(-/-)/ApoB(100/100)/IGFII mice, ATX is overexpressed and lysophosphatidic
      acid promotes a strong deposition of hydroxyapatite of calcium in aortic valve
      leaflets and accelerates the development of CAVD. CONCLUSIONS: ATX is transported
      in the aortic valve by Lp(a) and is also secreted by valve interstitial cells.
      ATX-lysophosphatidic acid promotes inflammation and mineralization of the aortic
      valve and thus could represent a novel therapeutic target in CAVD.

PMID- 26224811
TI  - Extracranial Systemic Embolic Events in Patients With Nonvalvular Atrial
      Fibrillation: Incidence, Risk Factors, and Outcomes.
AB  - BACKGROUND: Nonvalvular atrial fibrillation is a major cause of thromboembolic
      events. In comparison with atrial fibrillation-related stroke, extracranial
      systemic embolic events (SEEs) remain poorly defined. METHODS AND RESULTS: All
      suspected SEEs reported among 37 973 participants of 4 large contemporary
      randomized clinical trials of anticoagulation in atrial fibrillation were
      independently readjudicated for clinical and objective evidence of sudden loss of
      perfusion of a limb or organ. Over 91 746 patient-years of follow-up, 221 SEEs
      occurred in 219 subjects. The SEE incidence was 0.24 of 100 and stroke incidence
      was 1.92 of 100 patient-years. In comparison with patients with stroke, those
      with SEE were more often female (56% versus 47%; P=0.01) and had comparable mean
      age (73.1+/-8.5 versus 73.5+/-8.8 years; P=0.57) and mean CHADS2 scores (2.4+/
      1.3 versus 2.5+/-1.2; P=0.33). SEEs more frequently involved the lower extremity
      (58%) than visceral-mesenteric (31%) or upper extremity (10%). SEE-related care
      involved clinic assessment alone in 5%, 30% were hospitalized without procedures,
      60% underwent endovascular or surgical intervention, and 5% underwent amputation.
      Within 30 days, 54% of patients recovered fully, 20% survived with deficits, and
      25% died. Thirty-day mortality was greater after visceral-mesenteric than lower-
      or upper-extremity SEE (55%, 17%, and 9%, respectively, P<=0.0001). The relative
      risk of death throughout follow-up was 4.33 (95% confidence interval, 3.29-5.70)
      after SEE versus 6.79 (95% confidence interval, 6.22-7.41) after stroke in
      comparison with patients without either event. CONCLUSIONS: SEE constituted 11.5%
      of clinically recognized thromboembolic events in patients with atrial
      fibrillation and was associated with high morbidity and mortality. SEE mortality
      was comparable to that of ischemic stroke and varied by anatomic site.

PMID- 26224812
TI  - Systemic Embolic Events (SEE) in Atrial Fibrillation: SEEing Embolic Risk More
      Clearly.

PMID- 26224813
TI  - Unmet need, or need to ration?

PMID- 26224814
TI  - Cost effectiveness of percutaneous fixation with Kirschner wires versus locking
      plate for adult patients with a dorsally displaced fracture of the distal radius
      from the DRAFFT trial: a commentary.

PMID- 26224815
TI  - The influence of sagittal spinal deformity on anteversion of the acetabular
      component in total hip arthroplasty.
AB  - The interaction between the lumbosacral spine and the pelvis is dynamically
      related to positional change, and may be complicated by co-existing pathology.
      This review summarises the current literature examining the effect of sagittal
      spinal deformity on pelvic and acetabular orientation during total hip
      arthroplasty (THA) and provides recommendations to aid in placement of the
      acetabular component for patients with co-existing spinal pathology or long
      spinal fusions. Pre-operatively, patients can be divided into four categories
      based on the flexibility and sagittal balance of the spine. Using this
      information as a guide, placement of the acetabular component can be optimal
      based on the type and significance of co-existing spinal deformity.

PMID- 26224816
TI  - Adverse local tissue reactions in metal-on-polyethylene total hip arthroplasty
      due to trunnion corrosion: the risk of misdiagnosis.
AB  - Adverse reaction to wear and corrosion debris is a cause for concern in total hip
      arthroplasty (THA). Modular junctions are a potential source of such wear
      products and are associated with secondary pseudotumour formation. We present a
      consecutive series of 17 patients treated at our unit for this complication
      following metal-on-highly cross-linked polyethylene (MoP) THA. We emphasise the
      risk of misdiagnosis as infection, and present the aggregate laboratory results
      and pathological findings in this series. The clinical presentation was pain,
      swelling or instability. Solid, cystic and mixed soft-tissue lesions were noted
      on imaging and confirmed intra-operatively. Corrosion at the head-neck junction
      was noted in all cases. No bacteria were isolated on multiple pre- and intra
      operative samples yet the mean erythrocyte sedimentation rate was 49 (9 to 100)
      and C-reactive protein 32 (0.6 to 106) and stromal polymorphonuclear cell counts
      were noted in nine cases. Adverse soft-tissue reactions can occur in MoP THA
      owing to corrosion products released from the head-neck junction. The diagnosis
      should be carefully considered when investigating pain after THA. This may avoid
      the misdiagnosis of periprosthetic infection with an unidentified organism and
      mitigate the unnecessary management of these cases with complete single- or two
      stage exchange.

PMID- 26224817
TI  - Revision arthroplasty for periprosthetic femoral fracture using an uncemented
      modular tapered conical stem.
AB  - Periprosthetic femoral fracture (PFF) is a potentially devastating complication
      after total hip arthroplasty, with historically high rates of complication and
      failure because of the technical challenges of surgery, as well as the prevalence
      of advanced age and comorbidity in the patients at risk. This study describes the
      short-term outcome after revision arthroplasty using a modular, titanium,
      tapered, conical stem for PFF in a series of 38 fractures in 37 patients. The
      mean age of the cohort was 77 years (47 to 96). A total of 27 patients had an
      American Society of Anesthesiologists grade of at least 3. At a mean follow-up of
      35 months (4 to 66) the mean Oxford Hip Score (OHS) was 35 (15 to 48) and
      comorbidity was significantly associated with a poorer OHS. All fractures united
      and no stem needed to be revised. Three hips in three patients required further
      surgery for infection, recurrent PFF and recurrent dislocation and three other
      patients required closed manipulation for a single dislocation. One stem subsided
      more than 5 mm but then stabilised and required no further intervention. In this
      series, a modular, tapered, conical stem provided a versatile reconstruction
      solution with a low rate of complications.

PMID- 26224818
TI  - Revision total hip arthroplasty using cemented collarless double-taper femoral
      components at a mean follow-up of 13 years (8 to 20): an update.
AB  - The outcome of 219 revision total hip arthroplasties (THAs) in 98 male and 121
      female patients, using 137 long length and 82 standard length cemented collarless
      double-taper femoral stems in 211 patients, with a mean age of 72 years (30 to
      90) and mean follow-up of six years (two to 18) have been described previously.
      We have extended the follow-up to a mean of 13 years (8 to 20) in this cohort of
      patients in which the pre-operative bone deficiency Paprosky grading was IIIA or
      worse in 79% and 73% of femurs with long and standard stems, respectively. For
      the long stem revision group, survival to re-revision for aseptic loosening at 14
      years was 97% (95% confidence interval (CI) 91 to 100) and in patients aged > 70
      years, survival was 100%. Two patients (two revisions) were lost to follow-up and
      86 patients with 88 revisions had died. Worst-case analysis for survival to re
      revision for aseptic loosening at 14 years was 95% (95% CI 89 to 100) and 99%
      (95% CI 96 to 100) for patients aged > 70 years. One additional long stem was
      classified as loose radiographically but not revised. For the standard stem
      revision group, survival to re-revision for aseptic loosening at 14 years was 91%
      (95% CI 83 to 99). No patients were lost to follow-up and 49 patients with 51
      hips had died. No additional stems were classified as loose radiographically.
      Femoral revision using a cemented collarless double-taper stem, particularly with
      a long length stem, and in patients aged > 70 years, continues to yield excellent
      results up to 20 years post-operatively, including in hips with considerable
      femoral metaphyseal bone loss.

PMID- 26224819
TI  - The functional and financial impact of isolated and recurrent dislocation after
      total hip arthroplasty.
AB  - The aims of this study were to determine the functional impact and financial
      burden of isolated and recurrent dislocation after total hip arthroplasty (THA).
      Our secondary goal was to determine whether there was a difference between
      patients who were treated non-operatively and those who were treated operatively.
      We retrospectively reviewed 71 patients who had suffered dislocation of a primary
      THA. Their mean age was 67 years (41 to 92) and the mean follow-up was 3.8 years
      (2.1 to 8.2). Because patients with recurrent dislocation were three times more
      likely to undergo operative treatment (p < 0.0001), they ultimately had a
      significantly higher mean Harris Hip Score (HHS) (p = 0.0001), lower mean Western
      Ontario and McMaster Universities Arthritis Index (WOMAC) scores (p = 0.001) and
      a higher mean SF-12 score (p < 0.0001) than patients with a single dislocation.
      Likewise, those who underwent operative treatment had a higher mean HHS (p <
      0.0001), lower mean WOMAC score (p < 0.0001) and a higher mean SF-12 score (p <
      0.0001) than those who were treated non-operatively. Recurrent dislocation and
      operative treatment increased costs by 300% (L11 456; p < 0.0001) and 40% (L5217;
      p < 0.0001), respectively. The operative treatment of recurrent dislocation
      results in significantly better function than non-operative management. Moreover,
      the increase in costs for operative treatment is modest compared with that of non
      operative measures.

PMID- 26224820
TI  - Reconstruction of chronic abductor deficiency after revision hip arthroplasty
      using an extensor mechanism allograft.
AB  - This study reports the clinical outcome of reconstruction of deficient abductor
      muscles following revision total hip arthroplasty (THA), using a fresh-frozen
      allograft of the extensor mechanism of the knee. A retrospective analysis was
      conducted of 11 consecutive patients with a severe limp because of abductor
      deficiency which was confirmed on MRI scans. The mean age of the patients (three
      men and eight women) was 66.7 years (52 to 84), with a mean follow-up of 33
      months (24 to 41). Following surgery, two patients had no limp, seven had a mild
      limp, and two had a persistent severe limp (p = 0.004). The mean power of the
      abductors improved on the Medical Research Council scale from 2.15 to 3.8 (p <
      0.001). Pre-operatively, all patients required a stick or walking frame; post
      operatively, four patients were able to walk without an aid. Overall, nine
      patients had severe or moderate pain pre-operatively; ten patients had no or mild
      pain post-operatively. At final review, the Harris hip score was good in five
      patients, fair in two and poor in four. We conclude that using an extensor
      mechanism allograft is relatively effective in the treatment of chronic abductor
      deficiency of the hip after THA when techniques such as local tissue transfer are
      not possible. Longer-term follow-up is necessary before the technique can be
      broadly applied.

PMID- 26224821
TI  - The change in position of the sciatic nerve during the posterior approach to the
      hip.
AB  - The aim of this cadaver study was to identify the change in position of the
      sciatic nerve during arthroplasty using the posterior surgical approach to the
      hip. We investigated the position of the nerve during this procedure by
      dissecting 11 formalin-treated cadavers (22 hips: 12 male, ten female). The
      distance between the sciatic nerve and the femoral neck was measured before and
      after dislocation of the hip, and in positions used during the preparation of the
      femur. The nerve moves closer to the femoral neck when the hip is flexed to > 30
      degrees  and internally rotated to 90 degrees  (90 degrees  IR). The mean
      distance between the nerve and femoral neck was 43.1 mm (standard deviation (sd)
      8.7) with the hip at 0 degrees  of flexion and 90 degrees  IR; this significantly
      decreased to a mean of 36.1 mm (sd 9.5), 28.8 mm (sd 9.8) and 19.1 mm (sd 9.7) at
      30 degrees , 60 degrees  and 90 degrees  of hip flexion respectively (p < 0.001).
      In two hips the nerve was in contact with the femoral neck when the hip was
      flexed to 90 degrees . This study demonstrates that the sciatic nerve becomes
      closer to the operative field during hip arthroplasty using the posterior
      approach with progressive flexion of the hip.

PMID- 26224822
TI  - Function of the extensor mechanism of the knee after using the 'patellar-loop
      technique' to reconstruct the patellar tendon when replacing the proximal tibia
      for tumour.
AB  - The aim of this study was to analyse the gait pattern, muscle force and
      functional outcome of patients who had undergone replacement of the proximal
      tibia for tumour and alloplastic reconstruction of the extensor mechanism using
      the patellar-loop technique. Between February 1998 and December 2009, we carried
      out wide local excision of a primary sarcoma of the proximal tibia, proximal
      tibial replacement and reconstruction of the extensor mechanism using the
      patellar-loop technique in 18 patients. Of these, nine were available for
      evaluation after a mean of 11.6 years (0.5 to 21.6). The strength of the knee
      extensors was measured using an Isobex machine and gait analysis was undertaken
      in our gait assessment laboratory. Functional outcome was assessed using the
      American Knee Society (AKS) and Musculoskeletal Tumor Society (MSTS) scores. The
      gait pattern of the patients differed in ground contact time, flexion heel
      strike, maximal flexion loading response and total sagittal plane excursion. The
      mean maximum active flexion was 91 degrees  (30 degrees  to 110 degrees ). The
      overall mean extensor lag was 1 degrees  (0 degrees  to 5 degrees ). The mean
      extensor muscle strength was 25.8% (8.3% to 90.3%) of that in the non-operated
      leg (p < 0.001). The mean functional scores were 68.7% (43.4% to 83.3%) (MSTS)
      and 71.1 (30 to 90) (AKS functional score). In summary, the results show that
      reconstruction of the extensor mechanism using this technique gives good
      biomechanical and functional results. The patients' gait pattern is close to
      normal, except for a somewhat stiff knee gait pattern. The strength of the
      extensor mechanism is reduced, but sufficient for walking.

PMID- 26224823
TI  - A patient's recollection of pre-operative status is not accurate one year after
      arthroplasty of the hip or knee.
AB  - If patients could recall their physical status before total hip (THA) or knee
      arthroplasty (TKA) accurately it could have valuable applications both clinically
      and for research. This study evaluated the accuracy of a patient's recollection
      one year after either THA or TKA using the Oxford hip or knee scores (OHS and
      OKS). In total, 113 patients (59 THA, 54 TKA) who had completed the appropriate
      score pre-operatively were asked to complete the score again at a mean of 12.4
      months (standard deviation (sd) 0.8) after surgery, recalling their pre-operative
      state. While there were no significant differences between the actual and
      recalled pre-operative scores (OHS mean difference 0.8, sd 6.21, 95% confidence
      interval (CI) -0.82 to 2.42, p = 0.329; OKS mean difference -0.11, sd 7.34, 95%
      CI -2.11 to 1.89, p = 0.912), absolute differences were relatively large (OHS,
      5.24; OKS, 5.41), correlation was weak (OHS r = 0.7, OKS r = 0.61) and agreement
      between actual and recalled responses for individual questions was poor in half
      of the OHS and two thirds of the OKS. A patient's recollection of pre-operative
      pain and function is inaccurate one year after THA or TKA.

PMID- 26224824
TI  - The epidemiology of revision total knee and hip arthroplasty in England and
      Wales: a comparative analysis with projections for the United States. A study
      using the National Joint Registry dataset.
AB  - Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are recognised and
      proven interventions for patients with advanced arthritis. Studies to date have
      demonstrated a steady increase in the requirement for primary and revision
      procedures. Projected estimates made for the United States show that by 2030 the
      demand for primary TKA will grow by 673% and for revision TKA by 601% from the
      level in 2005. For THA the projected estimates are 174% and 137% for primary and
      revision surgery, respectively. The purpose of this study was to see if those
      predictions were similar for England and Wales using data from the National Joint
      Registry and the Office of National Statistics. Analysis of data for England and
      Wales suggest that by 2030, the volume of primary and revision TKAs will have
      increased by 117% and 332%, respectively between 2012 and 2030. The data for the
      United States translates to a 306% cumulative rate of increase between 2012 and
      2030 for revision surgery, which is similar to our predictions for England and
      Wales. The predictions from the United States for primary TKA were similar to our
      upper limit projections. For THA, we predicted an increase of 134% and 31% for
      primary and revision hip surgery, respectively. Our model has limitations,
      however, it highlights the economic burden of arthroplasty in the future in
      England and Wales as a real and unaddressed problem. This will have significant
      implications for the provision of health care and the management of orthopaedic
      services in the future.

PMID- 26224825
TI  - Cost effectiveness of treatment with percutaneous Kirschner wires versus volar
      locking plate for adult patients with a dorsally displaced fracture of the distal
      radius: analysis from the DRAFFT trial.
AB  - We present an economic evaluation using data from the Distal Radius Acute
      Fracture Fixation Trial (DRAFFT) to compare the relative cost effectiveness of
      percutaneous Kirschner wire (K-wire) fixation and volar locking-plate fixation
      for patients with dorsally-displaced fractures of the distal radius. The cost
      effectiveness analysis (cost per quality-adjusted life year; QALY) was derived
      from a multi-centre, two-arm, parallel group, assessor-blind, randomised
      controlled trial which took place in 18 trauma centres in the United Kingdom.
      Data from 460 patients were available for analysis, which includes both a
      National Health Service cost perspective including costs of surgery, implants and
      healthcare resource use over a 12-month period after surgery, and a societal
      perspective, which includes the cost of time off work and the need for additional
      private care. There was only a small difference in QALYs gained for patients
      treated with locking-plate fixation over those treated with K-wires. At a mean
      additional cost of L714 (95% confidence interval 588 to 865) per patient, locking
      plate fixation presented an incremental cost effectiveness ratio (ICER) of
      L89,322 per QALY within the first 12 months of treatment. Sensitivity analyses
      were undertaken to assess the ICER of locking-plate fixation compared with K
      wires. These were greater than L30,000. Compared with locking-plate fixation, K
      wire fixation is a 'cost saving' intervention, with similar health benefits.

PMID- 26224826
TI  - A combination of subscapularis tendon transfer and small-head hemiarthroplasty
      for cuff tear arthropathy: a pilot study.
AB  - This pilot study reports the clinical outcomes of a combination of partial
      subscapularis tendon transfer and small-head hemiarthroplasty in patients with
      rotatator cuff arthropathy. A total of 30 patients (30 shoulders; eight men and
      22 women) with a mean age of 74 years (55 to 84) were assessed at a mean follow
      up of 31 months (24 to 60). The inclusion criteria were painful cuff tear
      arthropathy with normal deltoid function and a non-degenerative subscapularis
      muscle and tendon and a preserved teres minor. Outcome was assessed using the
      University of California Los Angeles score, the Japanese Orthopaedic Association
      score, and the Oxford Shoulder Score. Radiographic measurements included the
      centre of rotation distance and the length of the deltoid. All clinical scores
      were significantly improved post-operatively. The active flexion and external
      rotation improved significantly at the most recent follow-up (p < 0.035).
      Although the mean centre of rotation distance changed significantly (p < 0.001),
      the mean length of the deltoid did not change significantly from the pre
      operative value (p = 0.29). The change in the length of the deltoid with < 100
      degrees  flexion was significantly less than that with > 100 degrees  (p <
      0.001). Progressive erosion of the glenoid was seen in four patients. No patient
      required revision or further surgery. A combination of partial subscapularis
      tendon transfer and small-head hemiarthroplasty effectively restored function and
      relieved pain in patients with rotator cuff arthropathy.

PMID- 26224827
TI  - Triceps-sparing ulnar approach for total elbow arthroplasty.
AB  - To prevent insufficiency of the triceps after total elbow arthroplasty, we have,
      since 2008, used a triceps-sparing ulnar approach. This study evaluates the
      clinical results and post-operative alignment of the prosthesis using this
      approach. We reviewed 25 elbows in 23 patients. There were five men and 18 women
      with a mean age of 69 years (54 to 83). There were 18 elbows with rheumatoid
      arthritis, six with a fracture or pseudoarthrosis and one elbow with
      osteoarthritis. Post-operative complications included one intra-operative
      fracture, one elbow with heterotopic ossification, one transient ulnar nerve
      palsy, and one elbow with skin necrosis, but no elbow was affected by
      insufficiency of the triceps. Patients were followed for a mean of 42 months (24
      to 77). The mean post-operative Japanese Orthopaedic Association Elbow Score was
      90.8 (51 to 100) and the mean Mayo Elbow Performance score 93.8 (65 to 100). The
      mean post-operative flexion/extension of the elbow was 135 degrees /-8 degrees .
      The Manual Muscle Testing score of the triceps was 5 in 23 elbows and 2 in two
      elbows (one patient). The mean alignment of the implants examined by 3D-CT was
      2.8 degrees  pronation (standard deviation (sd) 5.5), 0.3 degrees  valgus (sd
      2.7), and 0.7 degrees  extension (sd 3.2) for the humeral component, and 9.3
      degrees  pronation (sd 9.7), 0.3 degrees  valgus (sd 4.0), and 8.6 degrees 
      extension (sd 3.1) for the ulnar component. There was no radiolucent line or
      loosening of the implants on the final radiographs. The triceps-sparing ulnar
      approach allows satisfactory alignment of the implants, is effective in
      preventing post-operative triceps insufficiency, and gives satisfactory short
      term results.

PMID- 26224828
TI  - Decreasing spine implant costs and inter-physician cost variation: the impact of
      programme of cost containment on implant expenditure in spinal surgery.
AB  - The demand for spinal surgery and its costs have both risen over the past decade.
      In 2008 the aggregate hospital bill for surgical care of all spinal procedures
      was reported to be $33.9 billion. One key driver of rising costs is spinal
      implants. In 2011 our institution implemented a cost containment programme for
      spinal implants which was designed to reduce the prices of individual spinal
      implants and to reduce the inter-surgeon variation in implant costs. Between
      February 2012 and January 2013, our spinal surgeons performed 1493 spinal
      procedures using implants from eight different vendors. By applying market
      analysis and implant cost data from the previous year, we established references
      prices for each individual type of spinal implant, regardless of vendor, who were
      required to meet these unit prices. We found that despite the complexity of
      spinal surgery and the initial reluctance of vendors to reduce prices,
      significant savings were made to the medical centre.

PMID- 26224829
TI  - The number and characteristics of prevalent vertebral fractures in elderly men
      are associated with low bone mass and osteoporosis.
AB  - We sought to determine whether specific characteristics of vertebral fractures in
      elderly men are associated with low bone mineral density (BMD) and osteoporosis.
      Mister Osteoporosis Sweden is a population based cohort study involving 3014 men
      aged 69 to 81 years. Of these, 1427 had readable lateral radiographs of the
      thoracic and lumbar spine. Total body (TB) BMD (g/cm2) and total right hip (TH)
      BMD were measured by dual energy x-ray absorptiometry. The proportion of men with
      osteoporosis was calculated from TH BMD. There were 215 men (15.1%) with a
      vertebral fracture. Those with a fracture had lower TB BMD than those without (p
      < 0.001). Among men with a fracture, TB BMD was lower in those with more than
      three fractures (p = 0.02), those with biconcave fractures (p = 0.02) and those
      with vertebral body compression of > 42% (worst quartile) (p = 0.03). The mean
      odds ratio (OR) for having osteoporosis when having any type of vertebral
      fracture was 6.1 (95% confidence interval (CI) 3.9 to 9.5) compared with those
      without a fracture. A combination of more than three fractures and compression in
      the worst quartile had a mean OR of 114.2 (95% CI 6.7 to 1938.3) of having
      osteoporosis compared with those without a fracture. We recommend BMD studies to
      be undertaken in these subcohorts of elderly men with a vertebral fracture.

PMID- 26224830
TI  - The accuracy and safety of fluoroscopically guided percutaneous pedicle screws in
      the lumbosacral junction and the lumbar spine: a review of 880 screws.
AB  - We undertook a retrospective study investigating the accuracy and safety of
      percutaneous pedicle screws placed under fluoroscopic guidance in the lumbosacral
      junction and lumbar spine. The CT scans of patients were chosen from two centres:
      European patients from University Medical Center Hamburg-Eppendorf, Germany, and
      Asian patients from the University of Malaya, Malaysia. Screw perforations were
      classified into grades 0, 1, 2 and 3. A total of 880 percutaneous pedicle screws
      from 203 patients were analysed: 614 screws from 144 European patients and 266
      screws from 59 Asian patients. The mean age of the patients was 58.8 years (16 to
      91) and there were 103 men and 100 women. The total rate of perforation was 9.9%
      (87 screws) with 7.4% grade 1, 2.0% grade 2 and 0.5% grade 3 perforations. The
      rate of perforation in Europeans was 10.4% and in Asians was 8.6%, with no
      significant difference between the two (p = 0.42). The rate of perforation was
      the highest in S1 (19.4%) followed by L5 (14.9%). The accuracy and safety of
      percutaneous pedicle screw placement are comparable to those cited in the
      literature for the open method of pedicle screw placement. Greater caution must
      be taken during the insertion of L5 and S1 percutaneous pedicle screws owing to
      their more angulated pedicles, the anatomical variations in their vertebral
      bodies and the morphology of the spinal canal at this location.

PMID- 26224831
TI  - Return of functional mobility after an open tibial fracture: a sensor-based
      longitudinal cohort study using the Hamlyn Mobility Score.
AB  - In this study we quantified and characterised the return of functional mobility
      following open tibial fracture using the Hamlyn Mobility Score. A total of 20
      patients who had undergone reconstruction following this fracture were reviewed
      at three-month intervals for one year. An ear-worn movement sensor was used to
      assess their mobility and gait. The Hamlyn Mobility Score and its constituent
      kinematic features were calculated longitudinally, allowing analysis of mobility
      during recovery and between patients with varying grades of fracture. The mean
      score improved throughout the study period. Patients with more severe fractures
      recovered at a slower rate; those with a grade I Gustilo-Anderson fracture
      completing most of their recovery within three months, those with a grade II
      fracture within six months and those with a grade III fracture within nine
      months. Analysis of gait showed that the quality of walking continued to improve
      up to 12 months post-operatively, whereas the capacity to walk, as measured by
      the six-minute walking test, plateaued after six months. Late complications
      occurred in two patients, in whom the trajectory of recovery deviated by > 0.5
      standard deviations below that of the remaining patients. This is the first
      objective, longitudinal assessment of functional recovery in patients with an
      open tibial fracture, providing some clarification of the differences in
      prognosis and recovery associated with different grades of fracture.

PMID- 26224832
TI  - Diagnostic accuracy of the gravity stress test and clinical signs in cases of
      isolated supination-external rotation-type lateral malleolar fractures.
AB  - We prospectively assessed the diagnostic accuracy of the gravity stress test and
      clinical findings to evaluate the stability of the ankle mortise in patients with
      supination-external rotation-type fractures of the lateral malleolus without
      widening of the medial clear space. The cohort included 79 patients with a mean
      age of 44 years (16 to 82). Two surgeons assessed medial tenderness, swelling and
      ecchymosis and performed the external rotation (ER) stress test (a reference
      standard). A diagnostic radiographer performed the gravity stress test. For the
      gravity stress test, the positive likelihood ratio (LR) was 5.80 with a 95%
      confidence interval (CI) of 2.75 to 12.27, and the negative LR was 0.15 (95% CI
      0.07 to 0.35), suggesting a moderate change from the pre-test probability. Medial
      tenderness, both alone and in combination with swelling and/or ecchymosis,
      indicated a small change (positive LR, 2.74 to 3.25; negative LR, 0.38 to 0.47),
      whereas swelling and ecchymosis indicated only minimal changes (positive LR, 1.41
      to 1.65; negative LR, 0.38 to 0.47). In conclusion, when gravity stress test
      results are in agreement with clinical findings, the result is likely to predict
      stability of the ankle mortise with an accuracy equivalent to ER stress test
      results. When clinical examination suggests a medial-side injury, however, the
      gravity stress test may give a false negative result.

PMID- 26224833
TI  - Revisiting the 'bag of bones': functional outcome after the conservative
      management of a fracture of the distal humerus.
AB  - The best method of managing a fracture of the distal humerus in a frail low
      demand patient with osteoporotic bone remains controversial. Total elbow
      arthroplasty (TEA) has been recommended for patients in whom open reduction and
      internal fixation (ORIF) is not possible. Conservative methods of treatment,
      including the 'bag of bones' technique (acceptance of displacement of the bony
      fragments and early mobilisation), are now rarely considered as they are believed
      to give a poor functional result. We reviewed 40 elderly and low-demand patients
      (aged 50 to 93 years, 72% women) with a fracture of the distal humerus who had
      been treated conservatively at our hospital between March 2008 and December 2013,
      and assessed their short- and medium-term functional outcome. In the short-term,
      the mean Broberg and Morrey score improved from 42 points (poor; 23 to 80) at six
      weeks after injury to 67 points (fair; 40 to 88) by three months. In the medium
      term, surviving patients (n = 20) had a mean Oxford elbow score of 30 points (7
      to 48) at four years and a mean Disabilities of the Arm, Shoulder and Hand score
      of 38 points (0 to 75): 95% reported a functional range of elbow flexion. The
      cumulative rate of fracture union at one year was 53%. The mortality at five
      years approached 40%. Conservative management of a fracture of the distal humerus
      in a low-demand patient only gives a modest functional result, but avoids the
      substantial surgical risks associated with primary ORIF or TEA.

PMID- 26224834
TI  - The ongoing relevance of acetabular fracture classification.
AB  - The most widely used classification system for acetabular fractures was developed
      by Judet, Judet and Letournel over 50 years ago primarily to aid surgical
      planning. As population demographics and injury mechanisms have altered over
      time, the fracture patterns also appear to be changing. We conducted a
      retrospective review of the imaging of 100 patients with a mean age of 54.9 years
      (19 to 94) and a male to female ratio of 69:31 seen between 2010 and 2013 with
      acetabular fractures in order to determine whether the current spectrum of injury
      patterns can be reliably classified using the original system. Three consultant
      pelvic and acetabular surgeons and one senior fellow analysed anonymous imaging.
      Inter-observer agreement for the classification of fractures that fitted into
      defined categories was substantial, (kappa = 0.65, 95% confidence interval (CI)
      0.51 to 0.76) with improvement to near perfect on inclusion of CT imaging (kappa
      = 0.80, 95% CI 0.69 to 0.91). However, a high proportion of injuries (46%) were
      felt to be unclassifiable by more than one surgeon; there was moderate agreement
      on which these were (kappa = 0.42 95% CI 0.31 to 0.54). Further review of the
      unclassifiable fractures in this cohort of 100 patients showed that they tended
      to occur in an older population (mean age 59.1 years; 22 to 94 vs 47.2 years; 19
      to 94; p = 0.003) and within this group, there was a recurring pattern of
      anterior column and quadrilateral plate involvement, with or without an
      incomplete posterior element injury.

PMID- 26224835
TI  - Profiling microRNA expression in fracture nonunions: Potential role of microRNAs
      in nonunion formation studied in a rat model.
AB  - MicroRNAs (miRNAs ) are small non-coding RNAs that regulate gene expression. We
      hypothesised that the functions of certain miRNAs and changes to their patterns
      of expression may be crucial in the pathogenesis of nonunion. Healing fractures
      and atrophic nonunions produced by periosteal cauterisation were created in the
      femora of 94 rats, with 1:1 group allocation. At post-fracture days three, seven,
      ten, 14, 21 and 28, miRNAs were extracted from the newly generated tissue at the
      fracture site. Microarray and real-time polymerase chain reaction (PCR) analyses
      of day 14 samples revealed that five miRNAs, miR-31a-3p, miR-31a-5p, miR-146a-5p,
      miR-146b-5p and miR-223-3p, were highly upregulated in nonunion. Real-time PCR
      analysis further revealed that, in nonunion, the expression levels of all five of
      these miRNAs peaked on day 14 and declined thereafter. Our results suggest that
      miR-31a-3p, miR-31a-5p, miR-146a-5p, miR-146b-5p and miR-223-3p may play an
      important role in the development of nonunion. These findings add to the
      understanding of the molecular mechanism for nonunion formation and may lead to
      the development of novel therapeutic strategies for its treatment.

PMID- 26224836
TI  - The mechanical effects of extracorporeal irradiation on bone.
AB  - Extracorporeal irradiation of an excised tumour-bearing segment of bone followed
      by its re-implantation is a technique used in bone sarcoma surgery for limb
      salvage when the bone is of reasonable quality. There is no agreement among
      previous studies about the dose of irradiation to be given: up to 300 Gy have
      been used. We investigated the influence of extracorporeal irradiation on the
      elastic and viscoelastic properties of bone. Bone was harvested from mature
      cattle and subdivided into 13 groups: 12 were exposed to increasing levels of
      irradiation: one was not and was used as a control. The specimens, once
      irradiated, underwent mechanical testing in saline at 37 degrees C. The
      mechanical properties of each group, including Young's modulus, storage modulus
      and loss modulus, were determined experimentally and compared with the control
      group. There were insignificant changes in all of these mechanical properties
      with an increasing level of irradiation. We conclude that the overall mechanical
      effect of high levels of extracorporeal irradiation (300 Gy) on bone is
      negligible. Consequently the dose can be maximised to reduce the risk of local
      tumour recurrence.

PMID- 26224837
TI  - Key bioactive reaction products of the NO/H2S interaction are S/N-hybrid species,
      polysulfides, and nitroxyl.
AB  - Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S)
      signaling pathways are intimately intertwined, with mutual attenuation or
      potentiation of biological responses in the cardiovascular system and elsewhere.
      The chemical basis of this interaction is elusive. Moreover, polysulfides
      recently emerged as potential mediators of H2S/sulfide signaling, but their
      biosynthesis and relationship to NO remain enigmatic. We sought to characterize
      the nature, chemical biology, and bioactivity of key reaction products formed in
      the NO/sulfide system. At physiological pH, we find that NO and sulfide form a
      network of cascading chemical reactions that generate radical intermediates as
      well as anionic and uncharged solutes, with accumulation of three major products:
      nitrosopersulfide (SSNO(-)), polysulfides, and dinitrososulfite [N
      nitrosohydroxylamine-N-sulfonate (SULFI/NO)], each with a distinct chemical
      biology and in vitro and in vivo bioactivity. SSNO(-) is resistant to thiols and
      cyanolysis, efficiently donates both sulfane sulfur and NO, and potently lowers
      blood pressure. Polysulfides are both intermediates and products of SSNO(-)
      synthesis/decomposition, and they also decrease blood pressure and enhance
      arterial compliance. SULFI/NO is a weak combined NO/nitroxyl donor that releases
      mainly N2O on decomposition; although it affects blood pressure only mildly, it
      markedly increases cardiac contractility, and formation of its precursor sulfite
      likely contributes to NO scavenging. Our results unveil an unexpectedly rich
      network of coupled chemical reactions between NO and H2S/sulfide, suggesting that
      the bioactivity of either transmitter is governed by concomitant formation of
      polysulfides and anionic S/N-hybrid species. This conceptual framework would seem
      to offer ample opportunities for the modulation of fundamental biological
      processes governed by redox switching and sulfur trafficking. 

PMID- 26224838
TI  - Live-cell superresolution microscopy reveals the organization of RNA polymerase
      in the bacterial nucleoid.
AB  - Despite the fundamental importance of transcription, a comprehensive analysis of
      RNA polymerase (RNAP) behavior and its role in the nucleoid organization in vivo
      is lacking. Here, we used superresolution microscopy to study the localization
      and dynamics of the transcription machinery and DNA in live bacterial cells, at
      both the single-molecule and the population level. We used photoactivated single
      molecule tracking to discriminate between mobile RNAPs and RNAPs specifically
      bound to DNA, either on promoters or transcribed genes. Mobile RNAPs can explore
      the whole nucleoid while searching for promoters, and spend 85% of their search
      time in nonspecific interactions with DNA. On the other hand, the distribution of
      specifically bound RNAPs shows that low levels of transcription can occur
      throughout the nucleoid. Further, clustering analysis and 3D structured
      illumination microscopy (SIM) show that dense clusters of transcribing RNAPs form
      almost exclusively at the nucleoid periphery. Treatment with rifampicin shows
      that active transcription is necessary for maintaining this spatial organization.
      In faster growth conditions, the fraction of transcribing RNAPs increases, as
      well as their clustering. Under these conditions, we observed dramatic phase
      separation between the densest clusters of RNAPs and the densest regions of the
      nucleoid. These findings show that transcription can cause spatial reorganization
      of the nucleoid, with movement of gene loci out of the bulk of DNA as levels of
      transcription increase. This work provides a global view of the organization of
      RNA polymerase and transcription in living cells. 

PMID- 26224841
TI  - Evaluation of Two Phenotypic Screening Tests for Carbapenemase-Producing
      Enterobacteriaceae.
AB  - We evaluated the performance of two rapid tests for detection of carbapenemase
      producing Enterobacteriaceae (CPE) strains. The sensitivities and the
      specificities were 97.6% and 94.4% for the Rapid CARB Screen and 98.8% and 93.1%
      for the KPC/MBL & OXA-48 Confirm tests, providing the usefulness of these tools
      for screening CPE in microbiology wards. 

PMID- 26224840
TI  - Allocation of Klebsiella pneumoniae Bloodstream Isolates into Four Distinct
      Groups by ompK36 Typing in a Taiwanese University Hospital.
AB  - The OmpK36 porin plays a role in carbapenem resistance and may contribute to
      bacterial virulence in Klebsiella pneumoniae. This study aimed to investigate the
      characteristics of different groups of K. pneumoniae separated by ompK36 typing.
      Among 226 nonduplicate K. pneumoniae bloodstream isolates collected at a
      Taiwanese hospital in 2011, four ompK36 types, designated types A, B, C, and D,
      were identified by PCR in 61, 28, 100, and 36 isolates, respectively; 1 isolate
      was untypeable. Statistical analysis showed significantly higher rates of
      antimicrobial resistance (all tested antibiotics except meropenem), extended
      spectrum beta-lactamases or DHA-1 (47.5% together), Qnr-type quinolone resistance
      determinants (50.8%), and IncFIIA-type plasmids (49.2%) in group A than in
      others. Seventeen isolates were identified as belonging to 3 international high
      risk clones (4 sequence type 11 [ST11], 10 ST15, and 3 ST147 isolates); all
      isolates but 1 ST15 isolate were classified in group A. The significant
      characteristics of group C were hypermucoviscosity (62.0%) and a higher virulence
      gene content. This group included all serotype K1 (n = 30), K2 (n = 25), and K5
      (n = 3) isolates, 6 of 7 K57 isolates, all isolates of major clones associated
      with pyogenic liver abscesses (29 ST23, 11 ST65, 5 ST86, 7 ST373, and 1 ST375
      isolates), and 16 (94.1%) of 17 isolates causing bacteremic liver abscesses.
      Twelve (42.9%) of the group B isolates were responsible for bacteremic biliary
      tract infections. Group D was predominant (83.3%) among 12 K20 isolates. This
      study suggests that most clinical K. pneumoniae isolates can be allocated into
      four groups with distinct characteristics based on ompK36 types. 

PMID- 26224842
TI  - Leprosy Agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico: a
      Clarification.

PMID- 26224839
TI  - Na, K-ATPase alpha3 is a death target of Alzheimer patient amyloid-beta assembly.
AB  - Neurodegeneration correlates with Alzheimer's disease (AD) symptoms, but the
      molecular identities of pathogenic amyloid beta-protein (Abeta) oligomers and
      their targets, leading to neurodegeneration, remain unclear. Amylospheroids
      (ASPD) are AD patient-derived 10- to 15-nm spherical Abeta oligomers that cause
      selective degeneration of mature neurons. Here, we show that the ASPD target is
      neuron-specific Na(+)/K(+)-ATPase alpha3 subunit (NAKalpha3). ASPD-binding to
      NAKalpha3 impaired NAKalpha3-specific activity, activated N-type voltage-gated
      calcium channels, and caused mitochondrial calcium dyshomeostasis, tau
      abnormalities, and neurodegeneration. NMR and molecular modeling studies
      suggested that spherical ASPD contain N-terminal-Abeta-derived "thorns"
      responsible for target binding, which are distinct from low molecular-weight
      oligomers and dodecamers. The fourth extracellular loop (Ex4) region of NAKalpha3
      encompassing Asn(879) and Trp(880) is essential for ASPD-NAKalpha3 interaction,
      because tetrapeptides mimicking this Ex4 region bound to the ASPD surface and
      blocked ASPD neurotoxicity. Our findings open up new possibilities for knowledge
      based design of peptidomimetics that inhibit neurodegeneration in AD by blocking
      aberrant ASPD-NAKalpha3 interaction. 

PMID- 26224843
TI  - Cloacibacillus sp., a Potential Human Pathogen Associated with Bacteremia in
      Quebec and New Brunswick.
AB  - Bacteremia due to Cloacibacillus species is poorly described. We present three
      cases involving either Cloacibacillus evryensis or Cloacibacillus porcorum. The
      isolates were identified by 16S rRNA gene sequencing and were susceptible to
      antibiotics commonly used for anaerobic infections. The clinical significance of
      these organisms as potential emerging pathogens is discussed. 

PMID- 26224844
TI  - Differentiation of Acinetobacter Genomic Species 13BJ/14TU from Acinetobacter
      haemolyticus by Use of Matrix-Assisted Laser Desorption Ionization-Time of Flight
      Mass Spectrometry (MALDI-TOF MS).

PMID- 26224845
TI  - Transmission and Progression to Disease of Mycobacterium tuberculosis
      Phylogenetic Lineages in The Netherlands.
AB  - The aim of this study was to determine if mycobacterial lineages affect infection
      risk, clustering, and disease progression among Mycobacterium tuberculosis cases
      in The Netherlands. Multivariate negative binomial regression models adjusted for
      patient-related factors and stratified by patient ethnicity were used to
      determine the association between phylogenetic lineages and infectivity (mean
      number of positive contacts around each patient) and clustering (as defined by
      number of secondary cases within 2 years after diagnosis of an index case sharing
      the same fingerprint) indices. An estimate of progression to disease by each risk
      factor was calculated as a bootstrapped risk ratio of the clustering index by the
      infectivity index. Compared to the Euro-American reference, Mycobacterium
      africanum showed significantly lower infectivity and clustering indices in the
      foreign-born population, while Mycobacterium bovis showed significantly lower
      infectivity and clustering indices in the native population. Significantly lower
      infectivity was also observed for the East African Indian lineage in the foreign
      born population. Smear positivity was a significant risk factor for increased
      infectivity and increased clustering. Estimates of progression to disease were
      significantly associated with age, sputum-smear status, and behavioral risk
      factors, such as alcohol and intravenous drug abuse, but not with phylogenetic
      lineages. In conclusion, we found evidence of a bacteriological factor
      influencing indicators of a strain's transmissibility, namely, a decreased
      ability to infect and a lower clustering index in ancient phylogenetic lineages
      compared to their modern counterparts. Confirmation of these findings via follow
      up studies using tuberculin skin test conversion data should have important
      implications on M. tuberculosis control efforts. 

PMID- 26224846
TI  - Actinomyces Species Isolated from Breast Infections.
AB  - Actinomycosis is a chronic infection caused by Actinomyces species characterized
      by abscess formation, tissue fibrosis, and draining sinuses. The spectrum of
      infections caused by Actinomyces species ranges from classical invasive
      actinomycosis to a less invasive form of superficial skin and soft tissue
      infection. We present a review detailing all Actinomyces species isolated from
      breast infections in NHS Lothian between 2005 and 2013, Actinomyces species
      isolated from breast infections referred to the United Kingdom Anaerobe Reference
      Unit between 1988 and 2014, and cases describing Actinomyces breast infections
      published in the medical literature since 1994. Actinomyces species are
      fastidious organisms which can be difficult to identify and are likely to be
      underascertained as a cause of breast infections. Due to improved diagnostic
      methods, they are increasingly associated with chronic, recurrent breast
      infections and may play a more significant role in these infections than has
      previously been appreciated. 

PMID- 26224847
TI  - Direct Detection of Erythromycin-Resistant Bordetella pertussis in Clinical
      Specimens by PCR.
AB  - Resistance of Bordetella pertussis to erythromycin has been increasingly
      reported. We developed an allele-specific PCR method for rapid detection of
      erythromycin-resistant B. pertussis directly from nasopharyngeal (NP) swab
      samples submitted for diagnostic PCR. Based on the proven association of
      erythromycin resistance with the A2047G mutation in the 23S rRNA of B. pertussis,
      four primers, two of which were designed to be specific for either the wild-type
      or the mutant allele, were used in two different versions of the allele-specific
      PCR assay. The methods were verified with results obtained by PCR-based
      sequencing of 16 recent B. pertussis isolates and 100 NP swab samples submitted
      for diagnostic PCR. The detection limits of the two PCR assays ranged from 10 to
      100 fg per reaction for both erythromycin-susceptible and -resistant B.
      pertussis. Two amplified fragments of each PCR, of 286 and 112 bp, respectively,
      were obtained from a mutant allele of the isolates and/or NP swab samples
      containing B. pertussis DNAs. For the wild-type allele, only a 286-bp fragment
      was visible when the allele-specific PCR assay 1 was performed. No amplification
      was found when a number of non-Bordetella bacterial pathogens and NP swab samples
      that did not contain the DNAs of B. pertussis were examined. This assay can serve
      as an alternative for PCR-based sequencing, especially for local laboratories in
      resource-poor countries. 

PMID- 26224848
TI  - Clonogrouping, a Rapid Multiplex PCR Method for Identification of Major Clones of
      Listeria monocytogenes.
AB  - Three multiplex PCR assays were developed to identify the 11 most common Listeria
      monocytogenes clones in clinical and food samples; 270 (95.7%) of 282 strains of
      serogroups IVb, IIb, IIa, and IIc were identified accurately. This novel tool is
      a rapid and efficient alternative to multilocus sequence typing for
      identification of L. monocytogenes clones. 

PMID- 26224849
TI  - Making Memories That Last.

PMID- 26224850
TI  - Subthalamic Nucleus Cell-Specific Expression of Nicotinic Acetylcholine Receptors
      Uncovers Novel Basal Ganglia Microcircuits.

PMID- 26224851
TI  - Structural Variability within Frontoparietal Networks and Individual Differences
      in Attentional Functions: An Approach Using the Theory of Visual Attention.
AB  - Visuospatial attention allows us to select and act upon a subset of behaviorally
      relevant visual stimuli while ignoring distraction. Bundesen's theory of visual
      attention (TVA) (Bundesen, 1990) offers a quantitative analysis of the different
      facets of attention within a unitary model and provides a powerful analytic
      framework for understanding individual differences in attentional functions.
      Visuospatial attention is contingent upon large networks, distributed across both
      hemispheres, consisting of several cortical areas interconnected by long
      association frontoparietal pathways, including three branches of the superior
      longitudinal fasciculus (SLF I-III) and the inferior fronto-occipital fasciculus
      (IFOF). Here we examine whether structural variability within human
      frontoparietal networks mediates differences in attention abilities as assessed
      by the TVA. Structural measures were based on spherical deconvolution and
      tractography-derived indices of tract volume and hindrance-modulated
      orientational anisotropy (HMOA). Individual differences in visual short-term
      memory (VSTM) were linked to variability in the microstructure (HMOA) of SLF II,
      SLF III, and IFOF within the right hemisphere. Moreover, VSTM and speed of
      information processing were linked to hemispheric lateralization within the IFOF.
      Differences in spatial bias were mediated by both variability in microstructure
      and volume of the right SLF II. Our data indicate that the microstructural and
      macrostrucutral organization of white matter pathways differentially contributes
      to both the anatomical lateralization of frontoparietal attentional networks and
      to individual differences in attentional functions. We conclude that individual
      differences in VSTM capacity, processing speed, and spatial bias, as assessed by
      TVA, link to variability in structural organization within frontoparietal
      pathways. 

PMID- 26224852
TI  - Reelin Prevents Apical Neurite Retraction during Terminal Translocation and
      Dendrite Initiation.
AB  - The mechanisms controlling cortical dendrite initiation and targeting are poorly
      understood. Multiphoton imaging of developing mouse cortex reveals that apical
      dendrites emerge by direct transformation of the neuron's leading process during
      the terminal phase of neuronal migration. During this ~110 min period, the
      dendritic arbor increases ~2.5-fold in size and migration arrest occurs below the
      first stable branch point in the developing arbor. This dendritic outgrowth is
      triggered at the time of leading process contact with the marginal zone (MZ) and
      occurs primarily by neurite extension into the extracellular matrix of the MZ. In
      reeler cortices that lack the secreted glycoprotein Reelin, a subset of neurons
      completed migration but then retracted and reorganized their arbor in a
      tangential direction away from the MZ soon after migration arrest. For these
      reeler neurons, the tangential oriented primary neurites were longer lived than
      the radially oriented primary neurites, whereas the opposite was true of wild
      type (WT) neurons. Application of Reelin protein to reeler cortices destabilized
      tangential neurites while stabilizing radial neurites and stimulating dendritic
      growth in the MZ. Therefore, Reelin functions as part of a polarity signaling
      system that links dendritogenesis in the MZ with cellular positioning and
      cortical lamination. SIGNIFICANCE STATEMENT: Whether the apical dendrite emerges
      by transformation of the leading process of the migrating neuron or emerges de
      novo after migration is completed is unclear. Similarly, it is not clear whether
      the secreted glycoprotein Reelin controls migration and dendritic growth as
      related or separate processes. Here, multiphoton microscopy reveals the direct
      transformation of the leading process into the apical dendrite. This
      transformation is coupled to the successful completion of migration and neuronal
      soma arrest occurs below the first stable branch point of the nascent dendrite.
      Deficiency in Reelin causes the forming dendrite to avoid its normal target area
      and branch aberrantly, leading to improper cellular positioning. Therefore, this
      study links Reelin-dependent dendritogenesis with migration arrest and cortical
      lamination.

PMID- 26224853
TI  - Nonspecific Inhibition of the Motor System during Response Preparation.
AB  - Motor system excitability is transiently inhibited during the preparation of
      responses. Previous studies have attributed this inhibition to the operation of
      two mechanisms, one hypothesized to help resolve competition between alternative
      response options, and the other to prevent premature response initiation. By this
      view, inhibition should be restricted to task-relevant muscles. Although this
      prediction is supported in one previous study (Duque et al., 2010), studies of
      stopping ongoing actions suggest that some forms of motor inhibition may be
      widespread (Badry et al., 2009). This motivated us to conduct a series of
      transcranial magnetic stimulation (TMS) experiments to examine in detail the
      specificity of preparatory inhibition in humans. Motor-evoked potentials were
      inhibited in task-irrelevant muscles during response preparation, even when the
      muscles were contralateral and not homologous to the responding effector.
      Inhibition was also observed in both choice and simple response task conditions,
      with and without a preparatory interval. Control experiments ruled out that this
      inhibition is due to expectancy of TMS or a possible need to cancel the prepared
      response. These findings suggest that motor inhibition during response
      preparation broadly influences the motor system and likely reflects a process
      that occurs whenever a response is selected. We propose a reinterpretation of the
      functional significance of preparatory inhibition, one by which inhibition
      reduces noise to enhance signal processing and modulates the gain of a selected
      response. SIGNIFICANCE STATEMENT: Motor preparation entails the recruitment of
      excitatory and inhibitory neural mechanisms. The current experiments address the
      specificity of inhibitory mechanisms, asking whether preparatory inhibition
      affects task-irrelevant muscles. Participants prepared a finger movement to be
      executed at the end of a short delay period. Transcranial magnetic stimulation
      over primary motor cortex provided an assay of corticospinal excitability.
      Consistent with earlier work, the agonist muscle for the forthcoming response was
      inhibited during the preparatory period. Moreover, this inhibition was evident in
      task-irrelevant muscles, although the magnitude of inhibition depended on whether
      the response was fixed or involved a choice. These results implicate a broadly
      tuned inhibitory mechanism that facilitates response preparation, perhaps by
      lowering background activity before response initiation.

PMID- 26224854
TI  - Function and Circuitry of VIP+ Interneurons in the Mouse Retina.
AB  - Visual processing in the retina depends on coordinated signaling by interneurons.
      Photoreceptor signals are relayed to ~20 ganglion cell types through a dozen
      excitatory bipolar interneurons, each responsive to light increments (ON) or
      decrements (OFF). ON and OFF bipolar cell pathways become tuned through specific
      connections with inhibitory interneurons: horizontal and amacrine cells. A major
      obstacle for understanding retinal circuitry is the unknown function of most of
      the ~30-40 amacrine cell types, each of which synapses onto a subset of bipolar
      cell terminals, ganglion cell dendrites, and other amacrine cells. Here, we used
      a transgenic mouse line in which vasoactive intestinal polypeptide-expressing
      (VIP+) GABAergic interneurons express Cre recombinase. Targeted whole-cell
      recordings of fluorescently labeled VIP+ cells revealed three predominant types:
      wide-field bistratified and narrow-field monostratified cells with somas in the
      inner nuclear layer (INL) and medium-field monostratified cells with somas in the
      ganglion cell layer (GCL). Bistratified INL cells integrated excitation and
      inhibition driven by both ON and OFF pathways with little spatial tuning. Narrow
      field INL cells integrated excitation driven by the ON pathway and inhibition
      driven by both pathways, with pronounced hyperpolarizations at light offset.
      Monostratified GCL cells integrated excitation and inhibition driven by the ON
      pathway and showed center-surround spatial tuning. Optogenetic experiments showed
      that, collectively, VIP+ cells made strong connections with OFF delta, ON-OFF
      direction-selective, and W3 ganglion cells but weak, inconsistent connections
      with ON and OFF alpha cells. Revealing VIP+ cell morphologies, receptive fields
      and synaptic connections advances our understanding of their role in visual
      processing. SIGNIFICANCE STATEMENT: The retina is a model system for
      understanding nervous system function. At the first stage, rod and cone
      photoreceptors encode light and communicate with a complex network of
      interneurons. These interneurons drive the responses of ganglion cells, which
      form the optic nerve and transmit visual information to the brain. Presently, we
      lack information about many of the retina's inhibitory amacrine interneurons. In
      this study, we used genetically modified mice to study the light responses and
      intercellular connections of specific amacrine cell types. The results show
      diversity in the shape and function of the studied amacrine cells and elucidate
      their connections with specific types of ganglion cell. The findings advance our
      understanding of the cellular basis for retinal function.

PMID- 26224855
TI  - Negative Energy Balance Blocks Neural and Behavioral Responses to Acute Stress by
      "Silencing" Central Glucagon-Like Peptide 1 Signaling in Rats.
AB  - Previous reports indicate that caloric restriction attenuates anxiety and other
      behavioral responses to acute stress, and blunts the ability of stress to
      increase anterior pituitary release of adrenocorticotropic hormone. Since
      hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin
      releasing peptide (PrRP) neurons participate in behavioral and endocrine stress
      responses, and are sensitive to the metabolic state, we examined whether
      overnight food deprivation blunts stress-induced recruitment of these neurons and
      their downstream hypothalamic and limbic forebrain targets. A single overnight
      fast reduced anxiety-like behavior assessed in the elevated-plus maze and
      acoustic startle test, including marked attenuation of light-enhanced startle.
      Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure]
      robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted
      rats. Fasting also significantly blunted the ability of acute stress to activate
      c-Fos expression within the anterior ventrolateral bed nucleus of the stria
      terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats
      that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist
      blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP
      and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast
      "silences" GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic
      responses to acute stress. The partial mimicking of these fasting-induced effects
      in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential
      mechanism by which short-term negative energy balance attenuates neuroendocrine
      and behavioral responses to acute stress. SIGNIFICANCE STATEMENT: The results
      from this study reveal a potential central mechanism for the "metabolic tuning"
      of stress responsiveness. A single overnight fast, which markedly reduces anxiety
      like behavior in rats, reduces or blocks the ability of acute stress to activate
      hindbrain neurons that are immunoreactive for either prolactin-releasing peptide
      or glucagon-like peptide 1, and attenuates the activation of their stress
      sensitive projection targets in the limbic forebrain. In nonfasted rats, central
      antagonism of glucagon-like peptide 1 receptors partially mimics the effect of an
      overnight fast by blocking the ability of acute stress to inhibit food intake,
      and by attenuating stress-induced activation of hindbrain and limbic forebrain
      neurons. We propose that caloric restriction attenuates behavioral and
      physiological responses to acute stress by "silencing" central glucagon-like
      peptide 1 signaling pathways.

PMID- 26224856
TI  - IL-1alpha Gene Deletion Protects Oligodendrocytes after Spinal Cord Injury
      through Upregulation of the Survival Factor Tox3.
AB  - Spinal cord injury (SCI) causes the release of danger signals by stressed and
      dying cells, a process that leads to neuroinflammation. Evidence suggests that
      inflammation plays a role in both the damage and repair of injured neural tissue.
      We show that microglia at sites of SCI rapidly express the alarmin interleukin
      (IL)-1alpha, and that infiltrating neutrophils and macrophages subsequently
      produce IL-1beta. Infiltration of these cells is dramatically reduced in both IL
      1alpha(-/-) and IL-1beta(-/-) mice, but only IL-1alpha(-/-) mice showed rapid (at
      day 1) and persistent improvements in locomotion associated with reduced lesion
      volume. Similarly, intrathecal administration of the IL-1 receptor antagonist
      anakinra restored locomotor function post-SCI. Transcriptome analysis of SCI
      tissue at day 1 identified the survival factor Tox3 as being differentially
      regulated exclusively in IL-1alpha(-/-) mice compared with IL-1beta(-/-) and wild
      type mice. Accordingly, IL-1alpha(-/-) mice have markedly increased Tox3 levels
      in their oligodendrocytes, beginning at postnatal day 10 (P10) and persisting
      through adulthood. At P10, the spinal cord of IL-1alpha(-/-) mice showed a
      transient increase in mature oligodendrocyte numbers, coinciding with increased
      IL-1alpha expression in wild-type animals. In adult mice, IL-1alpha deletion is
      accompanied by increased oligodendrocyte survival after SCI. TOX3 overexpression
      in human oligodendrocytes reduced cellular death under conditions mimicking SCI.
      These results suggest that IL-1alpha-mediated Tox3 suppression during the early
      phase of CNS insult plays a crucial role in secondary degeneration. SIGNIFICANCE
      STATEMENT: The mechanisms underlying bystander degeneration of neurons and
      oligodendrocytes after CNS injury are ill defined. We show that microglia at
      sites of spinal cord injury (SCI) rapidly produce the danger signal interleukin
      (IL)-1alpha, which triggers neuroinflammation and locomotor defects. We uncovered
      that IL-1alpha(-/-) mice have markedly increased levels of the survival factor
      Tox3 in their oligodendrocytes, which correlates with the protection of this cell
      population, and reduced lesion volume, resulting in unprecedented speed, level,
      and persistence of functional recovery after SCI. Our data suggest that central
      inhibition of IL-1alpha or Tox3 overexpression during the acute phase of a CNS
      insult may be an effective means for preventing the loss of neurological function
      in SCI, or other acute injuries such as ischemia and traumatic brain injuries.

PMID- 26224858
TI  - Losing Control: Excessive Alcohol Seeking after Selective Inactivation of Cue
      Responsive Neurons in the Infralimbic Cortex.
AB  - Loss of control over drinking is a key deficit in alcoholism causally associated
      with malfunction of the medial prefrontal cortex (mPFC), but underlying molecular
      and cellular mechanisms remain unclear. Cue-induced reinstatement of alcohol
      seeking activates a subset of mPFC neurons in rats, identified by their common
      expression of the activity marker cFos and comprised of both principal and
      interneurons. Here, we used cFos-lacZ and pCAG-lacZ transgenic rats for activity
      dependent or nonselective inactivation of neurons, respectively, which by their
      lacZ encoded beta-galactosidase activity convert the inactive prodrug Daun02 into
      the neurotoxin daunorubicin. We report that activity-dependent ablation of a
      neuronal ensemble in the infralimbic but not the prelimbic subregion induced
      excessive alcohol seeking. The targeted neuronal ensemble was specific for the
      cue-induced response because stress-induced reinstatement was not affected in
      these animals. Importantly, nonselective inactivation of infralimbic neurons,
      using pCAG-lacZ rats, was without functional consequence on the cue-induced
      reinstatement task. Thus, inhibitory control over alcohol seeking is exerted by
      distinct functional ensembles within the infralimbic cortex rather than by a
      general inhibitory tone of this region on the behavioral output. This indicates a
      high level of functional compartmentation within the rat mPFC whereat many
      functional ensembles could coexist and interact within the same subregion.
      SIGNIFICANCE STATEMENT: Hebb's (1949) idea of memories as being represented in
      local neuronal networks is supported by identification of transiently stable
      activity patterns within subgroups of neurons. However, it is difficult to link
      individual networks to specific memory tasks, for example a learned behavior. By
      a novel approach of activity-dependent ablation, here we identify a specific
      neuronal ensemble located in the infralimbic subregion of the medial prefrontal
      cortex that controls a seeking response for alcohol in rats. Our data demonstrate
      that functional output depends on specific neuronal ensembles within a given
      brain region rather than on the global activity of that region, which raises
      important questions about the interpretation of numerous earlier experiments
      using site-directed silencing or stimulation for elucidating brain function.

PMID- 26224857
TI  - Trib3 Is Elevated in Parkinson's Disease and Mediates Death in Parkinson's
      Disease Models.
AB  - Parkinson's disease (PD) is characterized by the progressive loss of select
      neuronal populations, but the prodeath genes mediating the neurodegenerative
      processes remain to be fully elucidated. Trib3 (tribbles pseudokinase 3) is a
      stress-induced gene with proapoptotic activity that was previously described as
      highly activated at the transcriptional level in a 6-hydroxydopamine (6-OHDA)
      cellular model of PD. Here, we report that Trib3 immunostaining is elevated in
      dopaminergic neurons of the substantia nigra pars compacta (SNpc) of human PD
      patients. Trib3 protein is also upregulated in cellular models of PD, including
      neuronal PC12 cells and rat dopaminergic ventral midbrain neurons treated with 6
      OHDA, 1-methyl-4-phenylpyridinium (MPP+), or alpha-synuclein fibrils (alphaSYN).
      In the toxin models, Trib3 induction is substantially mediated by the
      transcription factors CHOP and ATF4. Trib3 overexpression is sufficient to
      promote neuronal death; conversely, Trib3 knockdown protects neuronal PC12 cells
      as well as ventral midbrain dopaminergic neurons from 6-OHDA, MPP+, or alphaSYN.
      Mechanism studies revealed that Trib3 physically interacts with Parkin, a
      prosurvival protein whose loss of function is associated with PD. Elevated Trib3
      reduces Parkin expression in cultured cells; and in the SNpc of PD patients,
      Parkin levels are reduced in a subset of dopaminergic neurons expressing high
      levels of Trib3. Loss of Parkin at least partially mediates the prodeath actions
      of Trib3 in that Parkin knockdown in cellular PD models abolishes the protective
      effect of Trib3 downregulation. Together, these findings identify Trib3 and its
      regulatory pathways as potential targets to suppress the progression of neuron
      death and degeneration in PD. SIGNIFICANCE STATEMENT: Parkinson's disease (PD) is
      the most common neurodegenerative movement disorder. Current treatments
      ameliorate symptoms, but not the underlying neuronal death. Understanding the
      core neurodegenerative processes in PD is a prerequisite for identifying new
      therapeutic targets and, ultimately, curing this disease. Here, we describe a
      novel pathway involving the proapoptotic protein Trib3 in neuronal death
      associated with PD. These findings are supported by data from multiple cellular
      models of PD and by immunostaining of postmortem PD brains. Upstream, Trib3 is
      induced by the transcription factors ATF4 and CHOP; and downstream, Trib3
      interferes with the PD-associated prosurvival protein Parkin to mediate death.
      These findings establish this new pathway as a potential and promising
      therapeutic target for treatment of PD.

PMID- 26224859
TI  - The Stress-Induced Atf3-Gelsolin Cascade Underlies Dendritic Spine Deficits in
      Neuronal Models of Tuberous Sclerosis Complex.
AB  - Hyperactivation of the mechanistic target of rapamycin (mTOR) kinase, as a result
      of loss-of-function mutations in tuberous sclerosis complex 1 (TSC1) or TSC2
      genes, causes protein synthesis dysregulation, increased cell size, and aberrant
      neuronal connectivity. Dysregulated synthesis of synaptic proteins has been
      implicated in the pathophysiology of autism spectrum disorder (ASD) associated
      with TSC and fragile X syndrome. However, cell type-specific translational
      profiles in these disease models remain to be investigated. Here, we used high
      fidelity and unbiased Translating Ribosome Affinity Purification (TRAP)
      methodology to purify ribosome-associated mRNAs and identified translational
      alterations in a rat neuronal culture model of TSC. We find that expression of
      many stress and/or activity-dependent proteins is highly induced while some
      synaptic proteins are repressed. Importantly, transcripts for the activating
      transcription factor-3 (Atf3) and mitochondrial uncoupling protein-2 (Ucp2) are
      highly induced in Tsc2-deficient neurons, as well as in a neuron-specific Tsc1
      conditional knock-out mouse model, and show differential responses to the mTOR
      inhibitor rapamycin. Gelsolin, a known target of Atf3 transcriptional activity,
      is also upregulated. shRNA-mediated block of Atf3 induction suppresses expression
      of gelsolin, an actin-severing protein, and rescues spine deficits found in Tsc2
      deficient neurons. Together, our data demonstrate that a cell-autonomous program
      consisting of a stress-induced Atf3-gelsolin cascade affects the change in
      dendritic spine morphology following mTOR hyperactivation. This previously
      unidentified molecular cascade could be a therapeutic target for treating
      mTORopathies. SIGNIFICANCE STATEMENT: Tuberous sclerosis complex (TSC) is a
      genetic disease associated with epilepsy and autism. Dysregulated protein
      synthesis has been implicated as a cause of this disease. However, cell type
      specific translational profiles that are aberrant in this disease are unknown.
      Here we show that expression of many stress and/or activity-dependent proteins is
      highly induced while some synaptic proteins are repressed in neurons missing the
      Tsc2 gene expression. Identification of genes whose translation is abnormal in
      TSC may provide insights to previously unidentified therapeutic targets.

PMID- 26224860
TI  - Differential Muscarinic Modulation in the Olfactory Bulb.
AB  - Neuromodulation of olfactory circuits by acetylcholine (ACh) plays an important
      role in odor discrimination and learning. Early processing of chemosensory
      signals occurs in two functionally and anatomically distinct regions, the main
      and accessory olfactory bulbs (MOB and AOB), which receive extensive cholinergic
      input from the basal forebrain. Here, we explore the regulation of AOB and MOB
      circuits by ACh, and how cholinergic modulation influences olfactory-mediated
      behaviors in mice. Surprisingly, despite the presence of a conserved circuit,
      activation of muscarinic ACh receptors revealed marked differences in cholinergic
      modulation of output neurons: excitation in the AOB and inhibition in the MOB.
      Granule cells (GCs), the most abundant intrinsic neuron in the OB, also exhibited
      a complex muscarinic response. While GCs in the AOB were excited, MOB GCs
      exhibited a dual muscarinic action in the form of a hyperpolarization and an
      increase in excitability uncovered by cell depolarization. Furthermore, ACh
      influenced the input-output relationship of mitral cells in the AOB and MOB
      differently showing a net effect on gain in mitral cells of the MOB, but not in
      the AOB. Interestingly, despite the striking differences in neuromodulatory
      actions on output neurons, chemogenetic inhibition of cholinergic neurons
      produced similar perturbations in olfactory behaviors mediated by these two
      regions. Decreasing ACh in the OB disrupted the natural discrimination of
      molecularly related odors and the natural investigation of odors associated with
      social behaviors. Thus, the distinct neuromodulation by ACh in these circuits
      could underlie different solutions to the processing of general odors and
      semiochemicals, and the diverse olfactory behaviors they trigger. SIGNIFICANCE
      STATEMENT: State-dependent cholinergic modulation of brain circuits is critical
      for several high-level cognitive functions, including attention and memory. Here,
      we provide new evidence that cholinergic modulation differentially regulates two
      parallel circuits that process chemosensory information, the accessory and main
      olfactory bulb (AOB and MOB, respectively). These circuits consist of remarkably
      similar synaptic arrangement and neuronal types, yet cholinergic regulation
      produced strikingly opposing effects in output and intrinsic neurons. Despite
      these differences, the chemogenetic reduction of cholinergic activity in freely
      behaving animals disrupted odor discrimination of simple odors, and the
      investigation of social odors associated with behaviors signaled by the
      Vomeronasal system.

PMID- 26224861
TI  - In Vivo Cochlear Hair Cell Generation and Survival by Coactivation of beta
      Catenin and Atoh1.
AB  - The mammalian cochlea exhibit minimal spontaneous regeneration, and loss of
      sensory hair cells (HCs) results in permanent hearing loss. In nonmammalian
      vertebrates, spontaneous HC regeneration occurs through both proliferation and
      differentiation of surrounding supporting cells (SCs). HC regeneration in
      postnatal mammalian cochleae in vivo remains limited by the small HC number and
      subsequent death of regenerated HCs. Here, we describe in vivo generation of 10
      fold more new HCs in the mouse cochlea than previously reported, most of which
      survive to adulthood. We achieved this by combining the expression of a
      constitutively active form of beta-catenin (a canonical Wnt activator) with
      ectopic expression of Atoh1 (a HC fate determination factor) in neonatal Lgr5+
      cells (the presumed SC and HC progenitors of the postnatal mouse cochlea), and
      discovered synergistic increases in proliferation and differentiation. The new
      HCs were predominantly located near the endogenous inner HCs, expressed early HC
      differentiation markers, and were innervated despite incomplete alignment of
      presynaptic and postsynaptic markers. Surprisingly, genetic tracing revealed that
      only a subset of Lgr5+ cells that lie medial to the inner HCs respond to this
      combination, highlighting a previously unknown heterogeneity that exists among
      Lgr5+ cells. Together, our data indicate that beta-catenin and Atoh1 mediate
      synergistic effects on both proliferation and differentiation of a subset of
      neonatal cochlear Lgr5+ cells, thus overcoming major limitations of HC
      regeneration in postnatal mouse cochleae in vivo. These results provide a basis
      for combinatorial therapeutics for hearing restoration. SIGNIFICANCE STATEMENT:
      Hearing loss in humans from aging, noise exposure, or ototoxic drugs (i.e.,
      cisplatin or some antibiotics) is permanent and affects every segments of the
      population, worldwide. However, birds, frog, and fish have the ability to recover
      hearing, and recent studies have focused on understanding and applying what we
      have learned from them for restoring hearing in humans. However, studies have
      been hampered by low efficiency, limited cell numbers, and subsequent death of
      these newly generated auditory cells. Here, we describe a combinatorial approach,
      which results in the generation of auditory cells in greater numbers than
      previously reported, with most of them surviving to adult ages in vivo. These
      results provide a basis for combinatorial therapeutics for hearing restoration
      efforts.

PMID- 26224862
TI  - Toll-Like Receptors Promote Mitochondrial Translocation of Nuclear Transcription
      Factor Nuclear Factor of Activated T-Cells in Prolonged Microglial Activation.
AB  - Microglia are resident macrophages in the CNS that scavenge pathogens, dying
      cells, and molecules using pattern recognition Toll-like receptors (TLRs).
      Nuclear factor of activated T-cells (NFAT) family transcription factors also
      regulate inflammatory responses in microglia. However, whether there exists cross
      talk between TLR and NFAT signaling is unclear. Here we show that chronic
      activation of murine microglia by prolonged stimulation of Toll-like receptor 4
      (TLR4) ligand lipopolysaccharides (LPSs) leads to unexpected translocation of
      NFAT1 into mitochondria. This mitochondrial import of NFAT1 is independent of
      calcium/calcineurin signaling. Instead, inhibition of Toll/interleukin 1 receptor
      domain-containing adapter-inducing interferon-beta (TRIF) pathway blocks the
      mitochondrial translocation of NFAT1. Functionally, inhibition of NFAT1 reduces
      the TRIF-mediated expression of interferon-beta and compromises the production of
      ATP and reactive oxygen species in LPS-treated microglia. Therefore, our findings
      reveal a new inflammatory signaling pathway that links TLR with NFAT in
      regulating cytokine production and mitochondrial activity during chronic
      microglial activation. SIGNIFICANCE STATEMENT: Nuclear factor of activated T
      cells (NFAT) family transcription factors are known to undergo nuclear
      translocation in response to inflammatory stimulation. In this study, we
      uncovered a surprise transportation of NFATs into mitochondria in microglia after
      a prolonged treatment with bacteria endotoxin lipopolysaccharides (LPSs). LPSs
      activated Toll-like receptor 4 and its downstream Toll/interleukin 1 receptor
      domain-containing adapter-inducing interferon-beta (TRIF) to regulate the
      mitochondrial translocation of NFAT in microglia, whereas genetic inhibition of
      NFAT1 compromised TRIF-mediated cytokine production and reduced ATP and reactive
      oxygen species generation. These findings reveal a previously undescribed
      mitochondrial translocation of NFAT in microglia responding to extended
      activation of Toll-like receptor-mediated signaling transduction pathways.

PMID- 26224864
TI  - Probiotics Improve Inflammation-Associated Sickness Behavior by Altering
      Communication between the Peripheral Immune System and the Brain.
AB  - Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis,
      inflammatory bowel disease, chronic liver disease) commonly develop debilitating
      symptoms (i.e., sickness behaviors) that arise from changes in brain function.
      The microbiota-gut-brain axis alters brain function and probiotic ingestion can
      influence behavior. However, how probiotics do this remains unclear. We have
      previously described a novel periphery-to-brain communication pathway in the
      setting of peripheral organ inflammation whereby monocytes are recruited to the
      brain in response to systemic TNF-alpha signaling, leading to microglial
      activation and subsequently driving sickness behavior development. Therefore, we
      investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters
      this periphery-to-brain communication pathway, thereby reducing subsequent
      sickness behavior development. Using a well characterized mouse model of liver
      inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness
      behavior development in mice with liver inflammation without affecting disease
      severity, gut microbiota composition, or gut permeability. Attenuation of
      sickness behavior development was associated with reductions in microglial
      activation and cerebral monocyte infiltration. These events were paralleled by
      changes in markers of systemic immune activation, including decreased circulating
      TNF-alpha levels. Our observations highlight a novel pathway through which
      probiotics mediate cerebral changes and alter behavior. These findings allow for
      the potential development of novel therapeutic interventions targeted at the gut
      microbiome to treat inflammation-associated sickness behaviors in patients with
      systemic inflammatory diseases. SIGNIFICANCE STATEMENT: This research shows that
      probiotics, when eaten, can improve the abnormal behaviors (including social
      withdrawal and immobility) that are commonly associated with inflammation.
      Probiotics are able to cause this effect within the body by changing how the
      immune system signals the brain to alter brain function. These findings broaden
      our understanding of how probiotics may beneficially affect brain function in the
      context of inflammation occurring within the body and may open potential new
      therapeutic alternatives for the treatment of these alterations in behavior that
      can greatly affect patient quality of life.

PMID- 26224863
TI  - Genetically Identified Suppressed-by-Contrast Retinal Ganglion Cells Reliably
      Signal Self-Generated Visual Stimuli.
AB  - Spike trains of retinal ganglion cells (RGCs) are the sole source of visual
      information to the brain; and understanding how the ~20 RGC types in mammalian
      retinae respond to diverse visual features and events is fundamental to
      understanding vision. Suppressed-by-contrast (SbC) RGCs stand apart from all
      other RGC types in that they reduce rather than increase firing rates in response
      to light increments (ON) and decrements (OFF). Here, we genetically identify and
      morphologically characterize SbC-RGCs in mice, and target them for patch-clamp
      recordings under two-photon guidance. We find that strong ON inhibition (glycine
      > GABA) outweighs weak ON excitation, and that inhibition (glycine > GABA)
      coincides with decreases in excitation at light OFF. These input patterns explain
      the suppressive spike responses of SbC-RGCs, which are observed in dim and bright
      light conditions. Inhibition to SbC-RGC is driven by rectified receptive field
      subunits, leading us to hypothesize that SbC-RGCs could signal pattern
      independent changes in the retinal image. Indeed, we find that shifts of random
      textures matching saccade-like eye movements in mice elicit robust inhibitory
      inputs and suppress spiking of SbC-RGCs over a wide range of texture contrasts
      and spatial frequencies. Similarly, stimuli based on kinematic analyses of mouse
      blinking consistently suppress SbC-RGC spiking. Receiver operating
      characteristics show that SbC-RGCs are reliable indicators of self-generated
      visual stimuli that may contribute to central processing of blinks and saccades.
      SIGNIFICANCE STATEMENT: This study genetically identifies and morphologically
      characterizes suppressed-by-contrast retinal ganglion cells (SbC-RGCs) in mice.
      Targeted patch-clamp recordings from SbC-RGCs under two-photon guidance elucidate
      the synaptic mechanisms mediating spike suppression to contrast steps, and reveal
      that SbC-RGCs respond reliably to stimuli mimicking saccade-like eye movements
      and blinks. The similarity of responses to saccade-like eye movements and blinks
      suggests that SbC-RGCs may provide a unified signal for self-generated visual
      stimuli.

PMID- 26224866
TI  - Neuroanatomical Markers of Social Hierarchy Recognition in Humans: A Combined
      ERP/MRI Study.
AB  - Social hierarchy is an ubiquitous principle of social organization across animal
      species. Although some progress has been made in our understanding of how humans
      infer hierarchical identity, the neuroanatomical basis for perceiving key social
      dimensions of others remains unexplored. Here, we combined event-related
      potentials and structural MRI to reveal the neuroanatomical substrates of early
      status recognition. We designed a covertly simulated hierarchical setting in
      which participants performed a task either with a superior or with an inferior
      player. Participants showed higher amplitude in the N170 component when presented
      with a picture of a superior player compared with an inferior player. Crucially,
      the magnitude of this effect correlated with brain morphology of the posterior
      cingulate cortex, superior temporal gyrus, insula, fusiform gyrus, and caudate
      nucleus. We conclude that early recognition of social hierarchies relies on the
      structural properties of a network involved in the automatic recognition of
      social identity. SIGNIFICANCE STATEMENT: Humans can perceive social hierarchies
      very rapidly, an ability that is key for social interactions. However, some
      individuals are more sensitive to hierarchical information than others.
      Currently, it is unknown how brain structure supports such fast-paced processes
      of social hierarchy perception and their individual differences. Here, we
      addressed this issue for the first time by combining the high temporal resolution
      of event-related potentials (ERPs) and the high spatial resolution of structural
      MRI. This methodological approach allowed us to unveil a novel association
      between ERP neuromarkers of social hierarchy perception and the morphology of
      several cortical and subcortical brain regions typically assumed to play a role
      in automatic processes of social cognition. Our results are a step forward in our
      understanding of the human social brain.

PMID- 26224865
TI  - Sustained Perceptual Deficits from Transient Sensory Deprivation.
AB  - Sensory pathways display heightened plasticity during development, yet the
      perceptual consequences of early experience are generally assessed in adulthood.
      This approach does not allow one to identify transient perceptual changes that
      may be linked to the central plasticity observed in juvenile animals. Here, we
      determined whether a brief period of bilateral auditory deprivation affects sound
      perception in developing and adult gerbils. Animals were reared with bilateral
      earplugs, either from postnatal day 11 (P11) to postnatal day 23 (P23) (a
      manipulation previously found to disrupt gerbil cortical properties), or from P23
      P35. Fifteen days after earplug removal and restoration of normal thresholds,
      animals were tested on their ability to detect the presence of amplitude
      modulation (AM), a temporal cue that supports vocal communication. Animals reared
      with earplugs from P11-P23 displayed elevated AM detection thresholds, compared
      with age-matched controls. In contrast, an identical period of earplug rearing at
      a later age (P23-P35) did not impair auditory perception. Although the AM
      thresholds of earplug-reared juveniles improved during a week of repeated
      testing, a subset of juveniles continued to display a perceptual deficit.
      Furthermore, although the perceptual deficits induced by transient earplug
      rearing had resolved for most animals by adulthood, a subset of adults displayed
      impaired performance. Control experiments indicated that earplugging did not
      disrupt the integrity of the auditory periphery. Together, our results suggest
      that P11-P23 encompasses a critical period during which sensory deprivation
      disrupts central mechanisms that support auditory perceptual skills. SIGNIFICANCE
      STATEMENT: Sensory systems are particularly malleable during development. This
      heightened degree of plasticity is beneficial because it enables the acquisition
      of complex skills, such as music or language. However, this plasticity comes with
      a cost: nervous system development displays an increased vulnerability to the
      sensory environment. Here, we identify a precise developmental window during
      which mild hearing loss affects the maturation of an auditory perceptual cue that
      is known to support animal communication, including human speech. Furthermore,
      animals reared with transient hearing loss display deficits in perceptual
      learning. Our results suggest that speech and language delays associated with
      transient or permanent childhood hearing loss may be accounted for, in part, by
      deficits in central auditory processing mechanisms.

PMID- 26224867
TI  - C-Terminally Truncated Forms of Tau, But Not Full-Length Tau or Its C-Terminal
      Fragments, Are Released from Neurons Independently of Cell Death.
AB  - Recent evidence suggests that tau aggregation may spread via extracellular
      release and subsequent uptake by synaptically connected neurons, but little is
      known about the processes by which tau is released or the molecular forms of
      extracellular tau. To gain insight into the nature of extracellular tau, we used
      highly sensitive ELISAs, which, when used in tandem, are capable of
      differentiating between full-length (FL) tau, mid-region-bearing fragments, and C
      terminal (CT) fragments. We applied these assays to the systematic study of the
      conditioned media of N2a cells, induced pluripotent stem cell-derived human
      cortical neurons, and primary rat cortical neurons, each of which was carefully
      assessed for viability. In all three neuronal models, the bulk of extracellular
      tau was free-floating and unaggregated and <0.2% was encapsulated in exosomes.
      Although most intracellular tau was FL, the majority of extracellular tau was CT
      truncated and appeared to be released both actively by living neurons and
      passively by dead cells. In contrast, only a small amount of extracellular tau
      was aggregation-competent tau (i.e., contained the microtubule-binding regions)
      and this material appears to be released solely due to a low level of cell death
      that occurs in all cell culture systems. Importantly, amyloid beta-protein
      (Abeta)-induced neuronal compromise significantly increased the quantity of all
      forms of extracellular tau, but the presence of Abeta before detectable cell
      compromise did not increase extracellular tau. Collectively, these results
      suggest that factors that induce neuronal death are likely to be necessary to
      initiate the extracellular spread of tau aggregation. SIGNIFICANCE STATEMENT:
      Recent studies suggest that the transfer of tau between neurons underlies the
      characteristic spatiotemporal progression of neurofibrillary pathology. We
      searched for tau in the conditioned medium of N2a cells, induced pluripotent stem
      cell-derived human cortical neurons, and primary rat cortical neurons and
      analyzed the material present using four different tau ELISAs. We demonstrate
      that the majority of tau released from healthy neurons is C-terminally truncated
      and lacks the microtubule-binding region (MTBR) thought necessary for self
      aggregation. A small amount of MTBR-containing tau is present outside of cells,
      but this appears to be solely due to cell death. Therefore, if propagation of tau
      aggregation is mediated by extracellular tau, our findings suggest that neuronal
      compromise is required to facilitate this process.

PMID- 26224868
TI  - Loss of Consciousness Is Associated with Stabilization of Cortical Activity.
AB  - What aspects of neuronal activity distinguish the conscious from the unconscious
      brain? This has been a subject of intense interest and debate since the early
      days of neurophysiology. However, as any practicing anesthesiologist can attest,
      it is currently not possible to reliably distinguish a conscious state from an
      unconscious one on the basis of brain activity. Here we approach this problem
      from the perspective of dynamical systems theory. We argue that the brain, as a
      dynamical system, is self-regulated at the boundary between stable and unstable
      regimes, allowing it in particular to maintain high susceptibility to stimuli. To
      test this hypothesis, we performed stability analysis of high-density
      electrocorticography recordings covering an entire cerebral hemisphere in monkeys
      during reversible loss of consciousness. We show that, during loss of
      consciousness, the number of eigenmodes at the edge of instability decreases
      smoothly, independently of the type of anesthetic and specific features of brain
      activity. The eigenmodes drift back toward the unstable line during recovery of
      consciousness. Furthermore, we show that stability is an emergent phenomenon
      dependent on the correlations among activity in different cortical regions rather
      than signals taken in isolation. These findings support the conclusion that
      dynamics at the edge of instability are essential for maintaining consciousness
      and provide a novel and principled measure that distinguishes between the
      conscious and the unconscious brain. SIGNIFICANCE STATEMENT: What distinguishes
      brain activity during consciousness from that observed during unconsciousness?
      Answering this question has proven difficult because neither consciousness nor
      lack thereof have universal signatures in terms of most specific features of
      brain activity. For instance, different anesthetics induce different patterns of
      brain activity. We demonstrate that loss of consciousness is universally and
      reliably associated with stabilization of cortical dynamics regardless of the
      specific activity characteristics. To give an analogy, our analysis suggests that
      loss of consciousness is akin to depressing the damper pedal on the piano, which
      makes the sounds dissipate quicker regardless of the specific melody being
      played. This approach may prove useful in detecting consciousness on the basis of
      brain activity under anesthesia and other settings.

PMID- 26224870
TI  - Linking Objects to Actions: Encoding of Target Object and Grasping Strategy in
      Primate Ventral Premotor Cortex.
AB  - Neural activity in ventral premotor cortex (PMv) has been associated with the
      process of matching perceived objects with the motor commands needed to grasp
      them. It remains unclear how PMv networks can flexibly link percepts of objects
      affording multiple grasp options into a final desired hand action. Here, we use a
      relational encoding approach to track the functional state of PMv neuronal
      ensembles in macaque monkeys through the process of passive viewing, grip
      planning, and grasping movement execution. We used objects affording multiple
      possible grip strategies. The task included separate instructed delay periods for
      object presentation and grip instruction. This approach allowed us to distinguish
      responses elicited by the visual presentation of the objects from those
      associated with selecting a given motor plan for grasping. We show that PMv
      continuously incorporates information related to object shape and grip strategy
      as it becomes available, revealing a transition from a set of ensemble states
      initially most closely related to objects, to a new set of ensemble patterns
      reflecting unique object-grip combinations. These results suggest that PMv
      dynamically combines percepts, gradually navigating toward activity patterns
      associated with specific volitional actions, rather than directly mapping
      perceptual object properties onto categorical grip representations. Our results
      support the idea that PMv is part of a network that dynamically computes motor
      plans from perceptual information. SIGNIFICANCE STATEMENT: The present work
      demonstrates that the activity of groups of neurons in primate ventral premotor
      cortex reflects information related to visually presented objects, as well as the
      motor strategy used to grasp them, linking individual objects to multiple
      possible grips. PMv could provide useful control signals for neuroprosthetic
      assistive devices designed to interact with objects in a flexible way.

PMID- 26224871
TI  - Dysfunctional Antibodies in the Tumor Microenvironment Associate with Impaired
      Anticancer Immunity.
AB  - PURPOSE: Studies have demonstrated that cancer-associated matrix
      metalloproteinases (MMP) can generate single peptide bond cleavages in the hinge
      region of immunoglobulin G1 (IgG1). This study investigated the cleavage of
      endogenous IgGs by MMPs in the tumor microenvironment and the consequences of the
      IgG hinge cleavage for humoral immunity. EXPERIMENTAL DESIGN: We investigated the
      occurrence of single peptide bond cleaved IgGs (scIgG) in tumor tissues and
      plasma samples collected from a cohort of breast cancer patients (n = 60).
      Samples from healthy people (n = 20) were used as the control. Antibody hinge
      cleavage was detected by multiple assays, including IHC, ELISA, and flow
      cytometry. A correlation analysis was conducted between scIgG levels and patient
      clinical parameters. RESULTS: Levels of scIgGs in tumors were significantly
      higher than in normal tissues. In addition, scIgG levels in tumors were enriched
      compared with that in the plasma of the same patients. The appearance of scIgGs
      in tumor tissues was associated with altered host IgG content and decreased IgG1.
      Increased tumor scIgGs were found to be positively correlated with adverse
      clinical factors, such as elevated tumor-associated macrophages, increased
      expression of MMP9 and other MMPs, and local metastasis to axillary lymph nodes.
      CONCLUSIONS: The study contributes to mounting evidence for the presence of hinge
      cleaved antibodies with reduced Fc immune effector function in the tumor
      microenvironment. The results highlight a link between tumor scIgGs and poor
      patient outcomes, and reveal a component of compromised humoral immunity within
      tumors that could point to new immunotherapeutic strategies to rescue host
      immunity.

PMID- 26224869
TI  - Reversal of Aging-Related Neuronal Ca2+ Dysregulation and Cognitive Impairment by
      Delivery of a Transgene Encoding FK506-Binding Protein 12.6/1b to the
      Hippocampus.
AB  - Brain Ca2+ regulatory processes are altered during aging, disrupting neuronal,
      and cognitive functions. In hippocampal pyramidal neurons, the Ca2+ -dependent
      slow afterhyperpolarization (sAHP) exhibits an increase with aging, which
      correlates with memory impairment. The increased sAHP results from elevated L
      type Ca2+ channel activity and ryanodine receptor (RyR)-mediated Ca2+ release,
      but underlying molecular mechanisms are poorly understood. Previously, we found
      that expression of the gene encoding FK506-binding protein 12.6/1b (FKBP1b), a
      small immunophilin that stabilizes RyR-mediated Ca2+ release in cardiomyocytes,
      declines in hippocampus of aged rats and Alzheimer's disease subjects.
      Additionally, knockdown/disruption of hippocampal FKBP1b in young rats augments
      neuronal Ca2+ responses. Here, we test the hypothesis that declining FKBP1b
      underlies aging-related hippocampal Ca2+ dysregulation. Using microinjection of
      adeno-associated viral vector bearing a transgene encoding FKBP1b into the
      hippocampus of aged male rats, we assessed the critical prediction that
      overexpressing FKBP1b should reverse Ca2+ -mediated manifestations of brain
      aging. Immunohistochemistry and qRT-PCR confirmed hippocampal FKBP1b
      overexpression 4-6 weeks after injection. Compared to aged vector controls, aged
      rats overexpressing FKBP1b showed dramatic enhancement of spatial memory, which
      correlated with marked reduction of sAHP magnitude. Furthermore, simultaneous
      electrophysiological recording and Ca2+ imaging in hippocampal neurons revealed
      that the sAHP reduction was associated with a decrease in parallel RyR-mediated
      Ca2+ transients. Thus, hippocampal FKBP1b overexpression reversed key aspects of
      Ca2+ dysregulation and cognitive impairment in aging rats, supporting the novel
      hypothesis that declining FKBP1b is a molecular mechanism underlying aging
      related Ca2+ dysregulation and unhealthy brain aging and pointing to FKBP1b as a
      potential therapeutic target. SIGNIFICANCE STATEMENT: This paper reports critical
      tests of a novel hypothesis that proposes a molecular mechanism of unhealthy
      brain aging and possibly, Alzheimer's disease. For more than 30 years, evidence
      has been accumulating that brain aging is associated with dysregulation of
      calcium in neurons. Recently, we found that FK506-binding protein 12.6/1b
      (FKBP1b), a small protein that regulates calcium, declines with aging in the
      hippocampus, a brain region important for memory. Here we used gene therapy
      approaches and found that raising FKBP1b reversed calcium dysregulation and
      memory impairment in aging rats, allowing them to perform a memory task as well
      as young rats. These studies identify a potential molecular mechanism of brain
      aging and may also have implications for treatment of Alzheimer's disease.

PMID- 26224872
TI  - Integrative Protein-Based Prognostic Model for Early-Stage Endometrioid
      Endometrial Cancer.
AB  - PURPOSE: Endometrioid endometrial carcinoma (EEC) is the major histologic type of
      endometrial cancer, the most prevalent gynecologic malignancy in the United
      States. EEC recurrence or metastasis is associated with a poor prognosis. Early
      stage EEC is generally curable, but a subset has high risk of recurrence or
      metastasis. Prognosis estimation for early-stage EEC mainly relies on
      clinicopathologic characteristics, but is unreliable. We aimed to identify
      patients with high-risk early-stage EEC who are most likely to benefit from more
      extensive surgery and adjuvant therapy by building a prognostic model that
      integrates clinical variables and protein markers. EXPERIMENTAL DESIGN: We used
      two large, independent early-stage EEC datasets as training (n = 183) and
      validation cohorts (n = 333), and generated the levels of 186 proteins and
      phosphoproteins using reverse-phase protein arrays. By applying an initial
      filtering and the elastic net to the training samples, we developed a prognostic
      model for overall survival containing two clinical variables and 18 protein
      markers and optimized the risk group classification. RESULTS: The Kaplan-Meier
      survival analyses in the validation cohort confirmed an improved discriminating
      power of our prognostic model for patients with early-stage EEC over key clinical
      variables (log-rank test, P = 0.565 for disease stage, 0.567 for tumor grade, and
      1.3 * 10(-4) for the integrative model). Compared with clinical variables (stage,
      grade, and patient age), only the risk groups defined by the integrative model
      were consistently significant in both univariate and multivariate analyses across
      both cohorts. CONCLUSIONS: Our prognostic model is potentially of high clinical
      value for stratifying patients with early-stage EEC and improving their treatment
      strategies.

PMID- 26224873
TI  - Tankyrase Inhibition Blocks Wnt/beta-Catenin Pathway and Reverts Resistance to
      PI3K and AKT Inhibitors in the Treatment of Colorectal Cancer.
AB  - PURPOSE: Oncogenic mutations in the KRAS/PI3K/AKT pathway are one of the most
      frequent alterations in cancer. Although PI3K or AKT inhibitors show promising
      results in clinical trials, drug resistance frequently emerges. We previously
      revealed Wnt/beta-catenin signaling hyperactivation as responsible for such
      resistance in colorectal cancer. Here we investigate Wnt-mediated resistance in
      patients treated with PI3K or AKT inhibitors in clinical trials and evaluate the
      efficacy of a new Wnt/tankyrase inhibitor, NVP-TNKS656, to overcome such
      resistance. EXPERIMENTAL DESIGN: Colorectal cancer patient-derived sphere
      cultures and mouse tumor xenografts were treated with NVP-TNKS656, in combination
      with PI3K or AKT inhibitors.We analyzed progression-free survival of patients
      treated with different PI3K/AKT/mTOR inhibitors in correlation with Wnt/beta
      catenin pathway activation, oncogenic mutations, clinicopathological traits, and
      gene expression patterns in 40 colorectal cancer baseline tumors. RESULTS:
      Combination with NVP-TNKS656 promoted apoptosis in PI3K or AKT inhibitor
      resistant cells with high nuclear beta-catenin content. High FOXO3A activity
      conferred sensitivity to NVP-TNKS656 treatment. Thirteen of 40 patients presented
      high nuclear beta-catenin content and progressed earlier upon PI3K/AKT/mTOR
      inhibition. Nuclear beta-catenin levels predicted drug response, whereas
      clinicopathologic traits, gene expression profiles, or frequent mutations (KRAS,
      TP53, or PIK3CA) did not. CONCLUSIONS: High nuclear beta-catenin content
      independently predicts resistance to PI3K and AKT inhibitors. Combined treatment
      with a Wnt/tankyrase inhibitor reduces nuclear beta-catenin, reverts such
      resistance, and represses tumor growth. FOXO3A content and activity predicts
      response to Wnt/beta-catenin inhibition and together with beta-catenin may be
      predictive biomarkers of drug response providing a rationale to stratify
      colorectal cancer patients to be treated with PI3K/AKT/mTOR and Wnt/beta-catenin
      inhibitors.

PMID- 26224874
TI  - Imaging Tumor Acidity: pH-Low Insertion Peptide Probe for Optoacoustic
      Tomography.
AB  - Optoacoustic tomography has been used for the detection of pancreatic ductal
      adenocarcinoma targeted by pH-low insertion peptide (pHLIP) conjugated to near
      infrared fluorescent dye. It was proved that tumor targeting is pH dependent. The
      approach could have major implication for detection and monitoring of pancreatic
      and other cancers.

PMID- 26224875
TI  - The persistent clustering of adult body mass index by school attended in
      adolescence.
AB  - BACKGROUND: It is well known that adolescent body mass index (BMI) shows school
      level clustering. We explore whether school-level clustering of BMI persists into
      adulthood. METHODS: Multilevel models nesting young adults in schools they
      attended as adolescents are fit for 3 outcomes: adolescent BMI, self-report adult
      BMI and measured adult BMI. Sex-stratified and race/ethnicity-stratified (black,
      Hispanic, white, other) analyses were also conducted. RESULTS: School-level
      clustering (wave 1 intraclass correlation coefficient (ICC)=1.3%) persists over
      time (wave 4 ICC=2%), and results are comparable across stratified analyses of
      both sexes and all racial/ethnic groups (except for Hispanics when measured BMIs
      are used). Controlling for BMI in adolescence partially attenuates this effect.
      CONCLUSIONS: School-level clustering of BMI persists into young adulthood.
      Possible explanations include the salience of school environments in establishing
      behaviours and trajectories, the selection of adult social networks that resemble
      adolescent networks and reinforce previous behaviours, and characteristics of
      school catchment areas associated with BMI.

PMID- 26224876
TI  - The caspase-3-p120-RasGAP module generates a NF-kappaB repressor in response to
      cellular stress.
AB  - The nuclear factor kappaB (NF-kappaB) transcription factor is a master regulator
      of inflammation. Short-term NF-kappaB activation is generally beneficial.
      However, sustained NF-kappaB might be detrimental, directly causing apoptosis of
      cells or leading to a persistent damaging inflammatory response. NF-kappaB
      activity in stressed cells needs therefore to be controlled for homeostasis
      maintenance. In mildly stressed cells, caspase-3 cleaves p120 RasGAP, also known
      as RASA1, into an N-terminal fragment, which we call fragment N. We show here
      that this fragment is a potent NF-kappaB inhibitor. Fragment N decreases the
      transcriptional activity of NF-kappaB by promoting its export from the nucleus.
      Cells unable to generate fragment N displayed increased NF-kappaB activation upon
      stress. Knock-in mice expressing an uncleavable p120 RasGAP mutant showed
      exaggerated NF-kappaB activation when their epidermis was treated with anthralin,
      a drug used for the treatment of psoriasis. Our study provides biochemical and
      genetic evidence of the importance of the caspase-3-p120-RasGAP stress-sensing
      module in the control of stress-induced NF-kappaB activation. 

PMID- 26224877
TI  - The lysine demethylase LSD1 is required for nuclear envelope formation at the end
      of mitosis.
AB  - The metazoan nucleus breaks down and reassembles during each cell division. Upon
      mitotic exit, the successful reestablishment of an interphase nucleus requires
      the coordinated reorganization of chromatin and formation of a functional nuclear
      envelope. Here, we report that the histone demethylase LSD1 (also known as KDM1A)
      plays a crucial role in nuclear assembly at the end of mitosis. Downregulation of
      LSD1 in cells extends telophase and impairs nuclear pore complex assembly. In
      vitro, LSD1 demethylase activity is required for the recruitment of MEL28 (also
      known as ELYS and AHCTF1) and nuclear envelope precursor vesicles to chromatin,
      crucial steps in nuclear reassembly. Accordingly, the formation of a closed
      nuclear envelope and nuclear pore complex assembly are impaired upon depletion of
      LSD1 or inhibition of its activity. Our results identify histone demethylation by
      LSD1 as a new regulatory mechanism linking the chromatin state and nuclear
      envelope formation at the end of mitosis. 

PMID- 26224878
TI  - Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary
      Hyperparathyroidism.
AB  - CKD and CKD-related mineral and bone disorders (CKD-MBDs) are associated with
      high cardiovascular and mortality risks. In randomized clinical trials (RCTs), no
      single drug intervention has been shown to reduce the high mortality risk in
      dialysis patients, but several robust secondary analyses point toward important
      potential beneficial effects of controlling CKD-MBD-related factors and secondary
      hyperparathyroidism. The advent of cinacalcet, which has a unique mode of action
      at the calcium-sensing receptor, represented an important step forward in
      controlling CKD-MBD. In addition, new RCTs have conclusively shown that
      cinacalcet improves achievement of target levels for all of the metabolic
      abnormalities associated with CKD-MBD and may also attenuate the progression of
      vascular and valvular calcifications in dialysis patients. However, a final
      conclusion on the effect of cinacalcet on hard outcomes remains elusive.
      Tolerance of cinacalcet is limited by frequent secondary side effects such as
      nausea, vomiting, hypocalcemia and oversuppression of parathyroid hormone, which
      may cause some management difficulties, especially for those lacking experience
      with the drug. Against this background, this review aims to summarize the results
      of studies on cinacalcet, up to and including the publication of the recent
      ADVANCE and EVOLVE RCTs, as well as recent post hoc analyses, and to offer
      practical guidance on how to improve the clinical management of the most frequent
      adverse events associated with cinacalcet, based on both currently available
      information and personal experience. In addition, attention is drawn to less
      common secondary effects of cinacalcet treatment and advisable precautions. 

PMID- 26224880
TI  - RootGraph: a graphic optimization tool for automated image analysis of plant
      roots.
AB  - This paper outlines a numerical scheme for accurate, detailed, and high
      throughput image analysis of plant roots. In contrast to existing root image
      analysis tools that focus on root system-average traits, a novel, fully automated
      and robust approach for the detailed characterization of root traits, based on a
      graph optimization process is presented. The scheme, firstly, distinguishes
      primary roots from lateral roots and, secondly, quantifies a broad spectrum of
      root traits for each identified primary and lateral root. Thirdly, it associates
      lateral roots and their properties with the specific primary root from which the
      laterals emerge. The performance of this approach was evaluated through
      comparisons with other automated and semi-automated software solutions as well as
      against results based on manual measurements. The comparisons and subsequent
      application of the algorithm to an array of experimental data demonstrate that
      this method outperforms existing methods in terms of accuracy, robustness, and
      the ability to process root images under high-throughput conditions. 

PMID- 26224881
TI  - Constraints to the potential efficiency of converting solar radiation into
      phytoenergy in annual crops: from leaf biochemistry to canopy physiology and crop
      ecology.
AB  - A new simple framework was proposed to quantify the efficiency of converting
      incoming solar radiation into phytoenergy in annual crops. It emphasizes the need
      to account for (i) efficiency gain when scaling up from the leaf level to the
      canopy level, and (ii) efficiency loss due to incomplete canopy closure during
      early and late phases of the crop cycle. Equations are given to estimate losses
      due to the constraints in various biochemical or physiological steps. For a given
      amount of daily radiation, a longer daytime was shown to increase energy use
      efficiency, because of the convex shape of the photosynthetic light response. Due
      to the higher cyclic electron transport, C4 leaves were found to have a lower
      energy loss via non-photochemical quenching, compared with C3 leaves. This
      contributes to the more linear light response in C4 than in C3 photosynthesis.
      Because of this difference in the curvature of the light response, canopy-to-leaf
      photosynthesis ratio, benefit from the optimum acclimation of the leaf nitrogen
      profile in the canopy, and productivity gain from future improvements in leaf
      photosynthetic parameters and canopy architecture were all shown to be higher in
      C3 than in C4 species. The indicative efficiency of converting incoming solar
      radiation into phytoenergy is ~2.2 and 3.0% in present C3 and C4 crops,
      respectively, when grown under well-managed conditions. An achievable efficiency
      via future genetic improvement was estimated to be as high as 3.6 and 4.1% for C3
      and C4 crops, respectively. 

PMID- 26224879
TI  - Pravastatin Therapy and Biomarker Changes in Children and Young Adults with
      Autosomal Dominant Polycystic Kidney Disease.
AB  - BACKGROUND AND OBJECTIVES: Disease-specific treatment options for autosomal
      dominant polycystic kidney disease are limited. Clinical intervention early in
      life is likely to have the greatest effect. In a 3-year randomized double-blind
      placebo-controlled phase 3 clinical trial, the authors recently showed that
      pravastatin decreased height-corrected total kidney volume (HtTKV) progression of
      structural kidney disease over a 3-year period. However, the underlying
      mechanisms have not been elucidated. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Participants were recruited nationally from July 2007 through
      October 2009. Plasma and urine samples collected at baseline, 18 months, and 36
      months from 91 pediatric patients enrolled in the above-mentioned clinical trial
      were subjected to mass spectrometry-based biomarker analysis. Changes in
      biomarkers over 3 years were compared between placebo and pravastatin-treated
      groups. Linear regression was used to evaluate the changes in biomarkers with the
      percent change in HtTKV over 3 years. RESULTS: Changes in plasma concentrations
      of proinflammatory and oxidative stress markers (9- hydroxyoctadecadienoic acid,
      13-hydroxyoctadecadienoic acid, and 15-hydroxyeicosatetraenoic acid [HETE]) over
      3 years were significantly different between the placebo and pravastatin-treated
      groups, with the pravastatin group showing a lower rate of biomarker increase.
      Urinary 8-HETE, 9-HETE, and 11-HETE were positively associated with the changes
      in HtTKV in the pravastatin group. CONCLUSIONS: Pravastatin therapy diminished
      the increase of cyclooxygenase- and lipoxygenase-derived plasma lipid mediators.
      The identified biomarkers and related molecular pathways of inflammation and
      endothelial dysfunction may present potential targets for monitoring of disease
      severity and therapeutic intervention of autosomal dominant polycystic kidney
      disease.

PMID- 26224882
TI  - Different 2-Aminothiazole Therapeutics Produce Distinct Patterns of Scrapie Prion
      Neuropathology in Mouse Brains.
AB  - Because no drug exists that halts or even slows any neurodegenerative disease,
      developing effective therapeutics for any prion disorder is urgent. We recently
      reported two compounds (IND24 and IND81) with the 2-aminothiazole (2-AMT)
      chemical scaffold that almost doubled the incubation times in scrapie prion
      infected, wild-type (wt) FVB mice when given in a liquid diet. Remarkably, oral
      prophylactic treatment with IND24 beginning 14 days prior to intracerebral prion
      inoculation extended survival from ~120 days to over 450 days. In addition to
      IND24, we evaluated the pharmacokinetics and efficacy of five additional 2-AMTs;
      one was not followed further because its brain penetration was poor. Of the
      remaining four new 2-AMTs, IND114338 doubled and IND125 tripled the incubation
      times of RML-inoculated wt and Tg4053 mice overexpressing wt mouse prion protein
      (PrP), respectively. Neuropathological examination of the brains from untreated
      controls showed a widespread deposition of self-propagating, beta-sheet-rich
      "scrapie" isoform (PrP(Sc)) prions accompanied by a profound astrocytic gliosis.
      In contrast, mice treated with 2-AMTs had lower levels of PrP(Sc) and associated
      astrocytic gliosis, with each compound resulting in a distinct pattern of
      deposition. Notably, IND125 prevented both PrP(Sc) accumulation and astrocytic
      gliosis in the cerebrum. Progressive central nervous system dysfunction in the
      IND125-treated mice was presumably due to the PrP(Sc) that accumulated in their
      brainstems. Disappointingly, none of the four new 2-AMTs prolonged the lives of
      mice expressing a chimeric human/mouse PrP transgene inoculated with Creutzfeldt
      Jakob disease prions. 

PMID- 26224884
TI  - Ectopic UCP1 Overexpression in White Adipose Tissue Improves Insulin Sensitivity
      in Lou/C Rats, a Model of Obesity Resistance.
AB  - Brown adipose tissue (BAT), characterized by the presence of uncoupling protein 1
      (UCP1), has been described as metabolically active in humans. Lou/C rats,
      originating from the Wistar strain, are resistant to obesity. We previously
      demonstrated that Lou/C animals express UCP1 in beige adipocytes in inguinal
      white adipose tissue (iWAT), suggesting a role of this protein in processes such
      as the control of body weight and the observed improved insulin sensitivity. A
      beta3 adrenergic agonist was administered for 2 weeks in Wistar and Lou/C rats to
      activate UCP1 and delineate its metabolic impact. The treatment brought about
      decreases in fat mass and improvements in insulin sensitivity in both groups. In
      BAT, UCP1 expression increased similarly in response to the treatment in the two
      groups. However, the intervention induced the appearance of beige cells in iWAT,
      associated with a marked increase in UCP1 expression, in Lou/C rats only. This
      increase was correlated with a markedly enhanced glucose uptake measured during
      euglycemic-hyperinsulinemic clamps, suggesting a role of beige cells in this
      process. Activation of UCP1 in ectopic tissues, such as beige cells in iWAT, may
      be an interesting therapeutic approach to prevent body weight gain, decrease fat
      mass, and improve insulin sensitivity. 

PMID- 26224886
TI  - Seven-Day Caloric and Saturated Fat Restriction Increases Myocardial Dietary
      Fatty Acid Partitioning in Impaired Glucose-Tolerant Subjects.
AB  - Subjects with impaired glucose tolerance (IGT) have increased myocardial
      partitioning of dietary fatty acids (DFAs) with left ventricular dysfunction,
      both of which are improved by modest weight loss over 1 year induced by lifestyle
      changes. Here, we determined the effects of a 7-day hypocaloric diet (-500
      kcal/day) low in saturated fat (<7% of energy) (LOWCAL study) versus isocaloric
      with the usual amount saturated fat (~10% of energy) diet (ISOCAL) on DFA
      metabolism in subjects with IGT. Organ-specific DFA partitioning and cardiac and
      hepatic DFA fractional uptake rates were measured in 15 IGT subjects (7 males/8
      females) using the oral 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid positron
      emission tomography method after 7 days of an ISOCAL diet versus a LOWCAL diet
      using a randomized crossover design. The LOWCAL diet led to reductions in weight
      and postprandial insulin area under the curve. Myocardial DFA partitioning over 6
      h was increased after the LOWCAL diet (2.3 +/- 0.1 vs. 1.9 +/- 0.2 mean standard
      uptake value, P < 0.04). However, the early (90-120 min) myocardial DFA
      fractional uptake was unchanged after the LOWCAL diet (0.055 +/- 0.025 vs. 0.046
      +/- 0.009 min(-1), P = 0.7). Liver DFA partitioning was unchanged, but liver
      fractional uptake of DFA tended to be increased. Very short-term caloric and
      saturated fat dietary restrictions do not lead to the same changes in organ
      specific DFA metabolism as those associated with weight loss in subjects with
      IGT.

PMID- 26224885
TI  - ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac
      Dysfunction in Response to Diet-Induced Obesity.
AB  - Obesity is increasing in prevalence and is strongly associated with metabolic and
      cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key
      pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2
      (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied
      the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and
      wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied
      at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased
      glucose intolerance, epicardial adipose tissue (EAT) inflammation, and
      polarization of macrophages into a proinflammatory phenotype in response to HFD.
      Similarly, human EAT in patients with obesity and heart failure displayed a
      proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD
      mice was associated with decreased myocardial adiponectin, decreased
      phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and
      myocardial insulin resistance, which worsened heart function. Ang 1-7 (24
      ug/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation
      and reduced cardiac steatosis and lipotoxicity, resulting in normalization of
      heart failure. In conclusion, ACE2 plays a novel role in heart disease associated
      with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation
      and cardiac insulin resistance.

PMID- 26224887
TI  - Natural Variation in Interleukin-2 Sensitivity Influences Regulatory T-Cell
      Frequency and Function in Individuals With Long-standing Type 1 Diabetes.
AB  - Defective immune homeostasis in the balance between FOXP3+ regulatory T cells
      (Tregs) and effector T cells is a likely contributing factor in the loss of self
      tolerance observed in type 1 diabetes (T1D). Given the importance of interleukin
      2 (IL-2) signaling in the generation and function of Tregs, observations that
      polymorphisms in genes in the IL-2 pathway associate with T1D and that some
      individuals with T1D exhibit reduced IL-2 signaling indicate that impairment of
      this pathway may play a role in Treg dysfunction and the pathogenesis of T1D.
      Here, we have examined IL-2 sensitivity in CD4+ T-cell subsets in 70 individuals
      with long-standing T1D, allowing us to investigate the effect of low IL-2
      sensitivity on Treg frequency and function. IL-2 responsiveness, measured by
      STAT5a phosphorylation, was a very stable phenotype within individuals but
      exhibited considerable interindividual variation and was influenced by T1D
      associated PTPN2 gene polymorphisms. Tregs from individuals with lower IL-2
      signaling were reduced in frequency, were less able to maintain expression of
      FOXP3 under limiting concentrations of IL-2, and displayed reduced suppressor
      function. These results suggest that reduced IL-2 signaling may be used to
      identify patients with the highest Treg dysfunction and who may benefit most from
      IL-2 immunotherapy.

PMID- 26224889
TI  - Single-incision laparoscopic management of a giant hepatic cyst.
AB  - Large symptomatic hepatic cysts may warrant surgical management. Traditional
      multiport laparoscopic technique is typically preferred over open laparotomy, but
      the use of the single-incision laparoscopic approach for this diagnosis is not
      well documented. Here, we describe the case of a 68-year-old woman who underwent
      complete anterior wall fenestration, excision and cauterization of a simple
      hepatic cyst via a single-incision laparoscopic technique through an incision at
      the umbilicus. The objective of this case report is to document single-incision
      laparoscopy as a safe, feasible and cosmetically appealing approach for the
      management of a large hepatic cyst. 

PMID- 26224883
TI  - Advances in the Diagnosis of Human Schistosomiasis.
AB  - Schistosomiasis is a major neglected tropical disease that afflicts more than 240
      million people, including many children and young adults, in the tropics and
      subtropics. The disease is characterized by chronic infections with significant
      residual morbidity and is of considerable public health importance, with
      substantial socioeconomic impacts on impoverished communities. Morbidity
      reduction and eventual elimination through integrated intervention measures are
      the focuses of current schistosomiasis control programs. Precise diagnosis of
      schistosome infections, in both mammalian and snail intermediate hosts, will play
      a pivotal role in achieving these goals. Nevertheless, despite extensive efforts
      over several decades, the search for sensitive and specific diagnostics for
      schistosomiasis is ongoing. Here we review the area, paying attention to earlier
      approaches but emphasizing recent developments in the search for new diagnostics
      for schistosomiasis with practical applications in the research laboratory, the
      clinic, and the field. Careful and rigorous validation of these assays and their
      cost-effectiveness will be needed, however, prior to their adoption in support of
      policy decisions for national public health programs aimed at the control and
      elimination of schistosomiasis. 

PMID- 26224890
TI  - An additional middle cuneiform?
AB  - Additional cuneiform bones of the foot have been described in reference to the
      medial bipartite cuneiform or as small accessory ossicles. An additional middle
      cuneiform has not been previously documented. We present the case of a patient
      with an additional ossicle that has the appearance and location of an additional
      middle cuneiform. Recognizing such an anatomical anomaly is essential for ruling
      out second metatarsal base or middle cuneiform fractures and for the preoperative
      planning of arthrodesis or open reduction and internal fixation procedures in
      this anatomical location. 

PMID- 26224888
TI  - Hypofractionated electron-beam radiation therapy for keloids: retrospective study
      of 568 cases with 834 lesions.
AB  - We aimed to analyze the outcomes of hypofractionated high-energy electron beam
      radiotherapy for the treatment of keloids. From February 1998 to January 2012,
      568 patients with a total of 834 keloids underwent radiotherapy: 826 lesions with
      postoperative radiotherapy, and 36 with skin-grafting. Lesion size was >5 cm in
      335 keloids. An electron-beam of 6 or 7 MeV was used, with a total dose of 18 Gy
      (two fractions with a 1-week interval) covering the lesion with a 1-cm margin.
      The time between surgery and radiotherapy was 24-48 h. Skin-grafted patients
      underwent radiotherapy 10-15 days after the operation. The median follow-up was
      40 months (range: 12-160 months). The local control rate was 88.25% (736/834).
      The relapse rate was 9.59% (80/834), and the time to relapse was 6-28 months
      (median: 12 months). Univariate analyses showed that gender, age, keloid size,
      keloid site, skin grafting, and operation-to-irradiation interval influenced the
      local control rate. Multivariate analysis showed that the relapse rate was
      correlated with gender (P = 0.048), age (P < 0.01), operation-to-irradiation
      interval (P < 0.01), keloid site (P < 0.01), surgical method (P = 0.04) and
      keloid size (P < 0.02). Adverse effects were observed in 9.83% (82/834). No
      radiation-induced cancers were observed. Hypofractionated high-energy electron
      beam radiotherapy for keloids yielded excellent outcomes, especially in cases
      without skin grafting. Early postoperative radiotherapy with limited
      hypofractionation could be a good choice for keloid treatment. 

PMID- 26224891
TI  - Cylindroma-like basaloid anal cancer presenting as a large pelvic mass in a
      patient with ulcerative colitis.
AB  - Basaloid cancers of the lower gastrointestinal tract are rare. The lack of
      mucosal involvement of this type of tumor is uncharacteristic and, to our
      knowledge, has not been described. In addition, the cylindroma-like appearance of
      this cancer has only a few examples in the literature. A 51-year-old male
      presented to us with a history of ulcerative colitis (UC) and obstruction of the
      anal canal. Imaging and colonoscopy revealed an entirely extraluminal tumor.
      Percutaneous biopsy yielded a diagnosis of cylindroma-like basaloid carcinoma of
      the anal region. Neoadjuvant chemotherapy and radiation resulted in stable
      disease by RECIST criteria. Surgical planning ensued, which led to R0 resection
      of the tumor, total colectomy and end ileostomy for his UC, and reconstruction of
      the perineal defect with a rectus myocutaneous flap. Surveillance at 6 months
      demonstrated no evidence of disease. 

PMID- 26224892
TI  - Influence of interface structure on mass transport in phase boundaries between
      different ionic materials: Experimental studies and formal considerations.
AB  - ABSTRACT: Internal and external interfaces in solids exhibit completely different
      transport properties compared to the bulk. Transport parallel to grain or phase
      boundaries is usually strongly enhanced. Transport perpendicular to an interface
      is usually blocked, i.e., transport across an interface is often much slower. Due
      to the high density of interfaces in modern micro- and nanoscaled devices, a
      severe influence on the total transport properties can be expected. In contrast
      to diffusion in metal grain boundaries, transport phenomena in boundaries of
      ionic materials are still less understood. The specific transport properties
      along metal grain boundaries are explained by structural factors like packing
      densities or dislocation densities in the interface region. In most studies
      dealing with ionic materials, the interfacial transport properties are merely
      explained by the influence of space charge regions. In this study the influence
      of the interface structure on the interfacial transport properties of ionic
      materials is discussed in analogy to metallic materials. A qualitative model
      based on the density of misfit dislocations and on interfacial strain is
      introduced for (untilted and untwisted) phase boundaries. For experimental
      verification, the interfacial ionic conductivity of different multilayer systems
      consisting of stabilised ZrO2 and an insulating oxide is investigated as a
      funtion of structural mismatch. As predicted by the model, the interfacial
      conductivity increases when the lattice mismatch is increased. GRAPHICAL
      ABSTRACT: 

PMID- 26224893
TI  - Gay-Straight Alliances, Social Justice Involvement, and School Victimization of
      Lesbian, Gay, Bisexual, and Queer Youth: Implications for School Well-Being and
      Plans to Vote.
AB  - Few studies have investigated school-based, positive development for lesbian,
      gay, bisexual, and queer (LGBQ) youth, despite knowledge of their heightened
      negative school experiences compared to heterosexual youth (e.g., school
      victimization). This study examines associations among participation in Gay
      Straight Alliance (GSA)-related social justice activities, GSA presence, and GSA
      membership with victimization based on sexual orientation and school-based well
      being (i.e., school safety, school belongingness, grade point average [GPA]) and
      future plans to vote. Using data from the Preventing School Harassment Study, a
      survey of 230 LGBQ students in 7th through 12th grades, the study finds that
      participation in GSA-related social justice activities and the presence of a GSA
      are positively associated with school belongingness and GPA. GSA membership is
      also positively associated with school belongingness. However, moderation
      analyses suggest that the positive benefits of GSA-related social justice
      involvement and the presence of a GSA dissipate at high levels of school
      victimization. Implications for schools are discussed.

PMID- 26224895
TI  - Pleiotropic Activities of Vitamin D Receptors - Adequate Activation for Multiple
      Health Outcomes.
AB  - The vitamin D receptor (VDR), a nuclear transcription factor, elicits
      physiological regulation of gene transcription following binding of its ligand,
      1,25-dihydroxyvitamin D. The major biological activities of vitamin D contribute
      to regulation of plasma calcium and phosphate homeostasis and bone remodeling,
      although recent evidence suggests that vitamin D, like other steroid hormone
      receptors, can regulate a diverse range of biological activities across many
      tissues. Such properties raise the notion that vitamin D deficiency may not only
      be detrimental to bone and muscular health, but also a risk factor for a number
      of adverse health outcomes including increased risk of cardiovascular disease,
      inflammation, immune system disorders and cancer. Advances in transcriptional
      research provide data not only on ligand-dependent activities of the VDR, but
      other activities of vitamin D extending to rapid modulation of intra-cellular
      signaling pathways as well as apparent ligand-independent interactions between
      the VDR and other transcriptionally active proteins. In this review, we detail
      the chief molecular activities of the VDR in regulating gene transcription,
      intracellular signaling and actions of VDR via binding to transcriptional
      regulating proteins. The breadth of biological activities attributed to vitamin D
      informs clinical biochemists and health care professionals on the implications of
      vitamin D deficiency for health. 

PMID- 26224896
TI  - Regional Variation in Analytical Techniques used in the Diagnosis and Monitoring
      of Porphyria: a Case for Harmonisation?
AB  - BACKGROUND: The Royal College of Pathologists of Australasia (RCPA) Porphyrin
      Quality Assurance Program assesses the measurement of urine, faecal, plasma and
      whole blood porphyrins and their components plus urinary porphobilinogen and
      delta aminolaevulinic acid and has laboratories enrolled from around the world.
      It was observed that there was a wide scatter in results submitted to some
      subsections of the program. METHODS: A detailed questionnaire covering the
      analytical techniques used in the diagnosis of porphyria was sent to all
      laboratories enrolled in the RCPA Porphyrin Quality Assurance Program.
      Additionally, self-enrolment data over a five year period was examined for
      trends/changes in standardisation, reagent sources and analytical technique.
      RESULTS: Twenty of the 45 laboratories enrolled in the Porphyrin Quality
      Assurance Program completed the survey, providing a snapshot of the analytical
      techniques used world-wide. Post survey self enrolment data indicated only little
      or no noticeable changes to analytical standardisation of techniques despite the
      continual lack of agreement of results in subsections of the External Quality
      Assurance program. CONCLUSIONS: While some aspects of porphyria testing are
      relatively consistent between laboratories, other diagnostic techniques vary
      widely. A wide variety of individualised reference intervals and reporting
      techniques is currently in use world-wide. While most of the participants in the
      survey are regional reference centres specialising in the diagnosis of porphyria
      and, as such, their diagnostic capability is not in question, international
      guidelines or global harmonisation of analytical techniques should allow better
      inter-laboratory comparisons to be made, ultimately improving diagnostic
      accuracy.

PMID- 26224897
TI  - Adventures with Creatinine and eGFR - A National, International and Personal
      Story - AACB Roman Lecture 2014.
AB  - In Australia and New Zealand today there is a commonality in all laboratories in
      many areas of testing related to Chronic Kidney Disease (CKD). These include
      creatinine assay standardisation, estimated Glomerular Filtration Rate (eGFR)
      reporting and the use of common units for serum creatinine and eGFR. This is
      supported by a single definition for diagnosis and staging of CKD, agreed
      indications for who and how to test together with detailed advice on test
      interpretation and patient management provided by our nephrology colleagues.
      These outcomes are the product of a decade of effort within Australia and New
      Zealand with collaboration between clinical disciplines and amongst laboratories.
      These local activities have been based on and supported by international actions
      in assay standardisation, eGFR formula development, understanding of clinical
      outcomes and guideline development. It is my belief that the local implementation
      of the current laboratory-based CKD testing processes is an outstanding example
      of good laboratory practice. This paper outlines the local and international
      activities and provides a view of my personal adventures with creatinine and
      eGFR. 

PMID- 26224894
TI  - Steroid Receptor-Associated Immunophilins: A Gateway to Steroid Signalling.
AB  - The steroid receptor-associated immunophilins FKBP51, FKBP52, CyP40 and PP5 have
      specific roles in steroid receptor function that impact steroid hormone-binding
      affinity, nucleocytoplasmic shuttling and transcriptional activation of target
      genes in a tissue-specific manner. Aberrant expression of these functionally
      unique immunophilins has the potential to cause steroid-based diseases, including
      breast and prostate cancer, diabetes and related metabolic disorders, male and
      female infertility and major depressive disorders. This review addresses the
      function of these proteins as co-chaperones in steroid receptor-Hsp90 complexes
      and extensively covers current knowledge of the link between the steroid receptor
      associated immunophilins and human disease. An improved understanding of their
      mechanisms of action has revealed opportunities for molecular therapies to
      enhance or inhibit cellular processes under immunophilin control that contribute
      both to human health and disease. 

PMID- 26224898
TI  - Ultra-low background measurements of decayed aerosol filters.
AB  - Aerosol samples collected on filter media were analyzed using HPGe detectors
      employing varying background-reduction techniques in order to experimentally
      evaluate the opportunity to apply ultra-low background measurement methods to
      samples collected, for instance, by the Comprehensive Test Ban Treaty
      International Monitoring System (IMS). In this way, realistic estimates of the
      impact of low-background methodology on the sensitivity obtained in systems such
      as the IMS were assessed. The current detectability requirement of stations in
      the IMS is 30 MUBq/m3 of air for 140Ba, which would imply ~106 fissions per daily
      sample. Importantly, this is for a fresh aerosol filter. One week of decay
      reduces the intrinsic background from radon daughters in the sample allowing much
      higher sensitivity measurement of relevant isotopes, including 131I. An
      experiment was conducted in which decayed filter samples were measured at a
      variety of underground locations using Ultra-Low Background (ULB) gamma
      spectroscopy technology. The impacts of the decay and ULB are discussed.

PMID- 26224899
TI  - Novel functionalized mesopore of SBA-15 as prospective sorbent for praseodymium
      and lutetium.
AB  - In the present work, results of gamma-irradiation on normal and functionalized
      SBA-15 by aurintricarboxylic acid have been reported. Characterization of normal
      and functionalized SBA-15 particles before and after gamma-irradiation was
      carried out using Fourier-transform infrared technique. Aurintricarboxylic acid
      ligand connected to SBA-15 was also analyzed using UV/Vis spectrophotometer. The
      modified sorbent was then used as a new sorbent for separation of trace amounts
      of praseodymium and lutetium ions from nuclear waste waters in batch techniques.
      Based on the results of distribution coefficients determination, and
      investigation of sorption process in various conditions, the parameters were
      optimized for separation lanthanides. It can be concluded that the functionalized
      SBA-15 is a promising sorbent for praseodymium and lutetium cations.

PMID- 26224900
TI  - Uranium isotopes in well water samples as drinking sources in some settlements
      around the Semipalatinsk Nuclear Test Site, Kazakhstan.
AB  - Radiochemical results of U isotopes (234U, 235U and 238U) and their activity
      ratios are reported for well waters as local sources of drinking waters collected
      from the ten settlements around the Semipalatinsk Nuclear Test Site (SNTS),
      Kazakhstan. The results show that 238U varies widely from 3.6 to 356 mBq/L (0.3
      28.7 MUg/L), with a factor of about 100. The 238U concentrations in some water
      samples from Dolon, Tailan, Sarzhal and Karaul settlements are comparable to or
      higher than the World Health Organization's restrictive proposed guideline of 15
      MUg (U)/L. The 234U/238U activity ratios in the measured water samples are higher
      than 1, and vary between 1.1 and 7.9, being mostly from 1.5 to 3. The measured
      235U/238U activity ratios are around 0.046, indicating that U in these well
      waters is of natural origin. It is probable that the elevated concentration of
      238U found in some settlements around the SNTS is not due to the close-in fallout
      from nuclear explosions at the SNTS, but rather to the intensive weathering of
      rocks including U there. The calculated effective doses to adults resulting from
      consumption of the investigated waters are in the range 1.0-18.7 MUSv/y. Those
      doses are lower than WHO and IAEA reference value (100 MUSv/y) for drinking
      water.

PMID- 26224901
TI  - Modified method of alpha determination in the 1/E1+alpha epithermal neutron
      spectrum of reactor.
AB  - A modified method has been developed for the alpha determination in the
      1/E1+alpha epithermal neutron spectrum of reactor. It is based on the Cd-covered
      and without Cd-covered irradiations of two monitors. This method was applied to
      determine the alpha value in the channels of Dalat reactor and the results were
      compared with those obtained by the other methods. It appeared that the results
      of the modified method were in quite good agreement with those of other methods.
      It also showed that the modified method was simple in practical uses and a good
      application in the experiment of alpha determination in the reactor irradiation
      channels.

PMID- 26224902
TI  - Is there a future for biomonitoring of elemental air pollution? A review focused
      on a larger-scaled health-related (epidemiological) context.
AB  - The present paper focuses on biomonitoring of elemental atmospheric pollution,
      which is reviewed in terms of larger-scaled biomonitoring surveys in an
      epidemiological context. Based on the literature information, today's
      availability of solar-powered small air filter samplers and fibrous ion exchange
      materials is regarded as adequate or an even better alternative for biomonitor
      transplant materials used in small-scaled set-ups, but biomonitors remain
      valuable in larger-scaled set-ups and in unforeseen releases and accidental
      situations. In the latter case, in-situ biomonitoring is seen as the only option
      for a retrospective study: biomoniors are there before one even knows that they
      are needed. For biomonitoring, nuclear analytical techniques are discussed as key
      techniques, especially because of the necessary multi-element assessments in both
      source recognition and single-element interpretation. To live up to the demands
      in an epidemiological context, larger-scaled in-situ biomonitoring asks for large
      numbers of samples, and consequently, for large total sample masses, this all to
      ensure representation of both local situations and survey area characteristics.
      Possibly, this point should direct studies into new "easy-to-sample" biomonitor
      organisms, of which high masses and numbers may be obtained in field work, rather
      than continue with biomonitors such as lichens. This also means that both sample
      handling and processing are of key importance in these studies. To avoid problems
      in comparability of analytical general procedures in milling, homogenization and
      digestion of samples of large masses, the paper proposes to involve only few but
      high-quality laboratories in the total element assessment routines. In this
      respect, facilities that can handle large sample masses in the assessment of
      element concentrations are to be preferred. This all highlights the involvement
      of large-sample-volume nuclear facilities, which, however, should be upgraded and
      automated in their operation to ensure the necessary sample throughput in larger
      scaled biomonitoring.

PMID- 26224903
TI  - Further results in search for transuranium elements in effluents discharged to
      air from nuclear power plants.
AB  - In this work we present data on transuranium nuclides 238Pu, 239,240Pu, 241Am,
      242Cm and 244Cm in effluents discharged to air (activity concentrations and
      annually discharged activities of individual radionuclides) from 7 stacks in 2004
      2009. In the effluents discharged to air from one stack low activities of
      transuranium nuclides were observed throughout the studied period. Transuranium
      nuclides had been discharged to air from this stack also in previous years since
      1996 when defect in the cladding of a fuel element and consequent contamination
      of the primary circuit occurred. In the effluents discharged to air from another
      stack transuranium nuclides were observed only in some monitoring periods of
      studied years. We could not prove the presence of transuranium nuclides in the
      effluents of the other stacks up to 2006. The transuranium nuclides in discharged
      effluents were registered in the second half-year of 2006. In 2007-2008
      especially low activities of 241Am were found in these effluents.

PMID- 26224904
TI  - Determination of 210Po and uranium in high salinity water samples.
AB  - A method for the determination of uranium and 210Po in high salinity water
      samples has been elaborated. Both radionuclides are preconcentrated from 0.5 dm3
      saline media by co-precipitation with hydrated manganese dioxide, followed by
      dissolution of the precipitate in 200 mL of 1 M HCl. Uranium isotopes 235U and
      238U can be directly determined by ICP MS method with a detection limit of 0.01
      ppb for 238U. Prior to a selective determination of 210Po, the majority of other
      naturally occurring alpha-emitting radionuclides (uranium, thorium and
      protactinium) can be stripped from this solution by their extraction with a 50%
      solution of HDEHP in toluene. Finally, 210Po is simply separated by direct
      transfer to an extractive scintillator containing 5% of trioctylphosphine oxide
      in Ultima Gold F cocktail and determined by an alpha/beta separation liquid
      scintillation technique with detection limit below 0.1 mBq/dm3.

PMID- 26224905
TI  - Why is monoalkylation versus bis-alkylation of the Ni(II) complex of the Schiff
      base of (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide and glycine so
      selective? MP2 modelling and topological QTAIM analysis of chiral metallocomplex
      synthons of alpha-amino acids used for the preparation of radiopharmaceuticals
      for positron emission tomography.
AB  - Chiral Ni(II) complexes are used for the preparation of carbon-11 or fluorine-18
      enantiomerically pure alpha-amino acids for positron emission tomography (PET).
      They enable the selective monoalkylation of a glycine synthon with high
      stereoselectivity and the preparation of enantiomerically pure alpha-amino acids
      with quarternary alpha-carbon. Molecular modelling of non-, mono- and di
      substituted complexes using quantum theory of atoms-in-molecule (QTAIM)
      topological analysis of electron density allowed us to formulate a new theory
      explaining the reasons for highly selective monomethylation of the complexes. In
      the non-substituted complex (GK), the alpha-carbon atom exhibits a higher atomic
      volume and a more positive charge in comparison with mono- and di-substituted
      complexes. This unusual behaviour is accompanied by increasing the bond critical
      point (BCP) ellipticity of the iminic bond in GK explained by the higher
      mechanical strain. Both phenomena indicate the increased reactivity and probably
      originate in more compact core of GK where shorter distances in the internal
      coordination sphere result in the higher strain of its bonds.

PMID- 26224907
TI  - Determination of neutron temperature in irradiation channels of reactor.
AB  - The neutron temperature is a characteristic parameter in irradiation channels of
      reactor. For nuclides which have resonances in the thermal neutron energy range,
      their Westcott g-factors are different from unity. The values of g-factors and
      cross-sections of (n, gamma) reaction of these nuclides are temperature
      dependence. The standard energy for tabulation of thermal neutron cross-section
      (sigma0) is that of room temperature (293.59 K or 20.43  degrees C),
      corresponding to a neutron energy 0.0253 eV or to a neutron velocity of 2200 m/s.
      However, in the irradiation channels of reactor, the temperature is not exact at
      20.43  degrees C. Thus, the temperature at the irradiation position must be known
      to convert sigma0 to sigma(T). A method for determination of the neutron
      temperature in irradiation channels of Dalat reactor is presented by fitting the
      thermal neutron spectrum obtained from the calculation using MCNP code.

PMID- 26224906
TI  - Preparation of 99mTc-PQQ and preliminary biological evaluation for the NMDA
      receptor.
AB  - Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox
      modulator and nerve growth factor found in a class of enzymes called
      quinoproteins, was labeled with 99mTc by using stannous fluoride (SnF2) method.
      Radiolabeling qualification, quality control and characterization of 99mTc-PQQ
      and its biodistribution studies in mice were performed and discussed. Effects of
      pH values, temperature, time and reducing agents concentration on the
      radiolabeling yield were investigated. The quality control procedure of 99mTc-PQQ
      was determined by thin layer chromatography (TLC), radio high-performance liquid
      chromatography (RHPLC) and paper electrophoresis methods. The average
      radiolabeling yield was 94 +/- 1% under optimum conditions of 0.99 mg of PQQ, 30
      MUg of SnF2, 0.5 mg of ethylenediaminetetraacetic acid disodium salt (EDTA-2Na)
      and 18.5 MBq of Na99mTcO4 at pH 6 and 25  degrees C with a response volume of 1
      +/- 0.1 mL. 99mTc-PQQ was stable and anionic. Lipid-water partition coefficient
      of 99mTc-PQQ was -1.49 +/- 0.16. The pharmacokinetics parameters of 99mTc-PQQ
      were t1/2alpha = 18.16 min, t1/2beta = 100.45 min, K12 = 0.013 min-1, K21 = 0.017
      min-1, Ke = 0.016 min-1, AUC (area under the curve) = 1040.78 ID% g-1 min and CL
      (plasma clearance) = 0.096 mL min-1. The dual-exponential equation was Y = 10.88e
      0.038t  + 5.21e-0.0069t . The biodistribution of 99mTc-PQQ was studied in ICR
      (Institute for Cancer Research 7701 Burhelme Are., Fox Chase, Philadelphia, PA
      1911 USA) mice. In vitro autoradiographic studies clearly showed that the 99mTc
      PQQ radioactivity accumulated predominantly in the hippocampus and cortex, which
      had a high density of N-methyl-d-aspartate Receptor (NMDAR). The enrichment can
      be blocked by NMDAR redox modulatory site antagonists-ebselen (EB) and 99mTc-PQQ
      is therefore a promising candidate for the molecular imaging of NMDAR. To date,
      however, there have been no studies characterizing 99mTc-PQQ.

PMID- 26224908
TI  - Reduction of 68Ge activity containing liquid waste from 68Ga PET chemistry in
      nuclear medicine and radiopharmacy by solidification.
AB  - PET with 68Ga from the TiO2- or SnO2- based 68Ge/68Ga generators is of increasing
      interest for PET imaging in nuclear medicine. In general, radionuclidic purity
      (68Ge vs. 68Ga activity) of the eluate of these generators varies between 0.01
      and 0.001%. Liquid waste containing low amounts of 68Ge activity is produced by
      eluting the 68Ge/68Ga generators and residues from PET chemistry. Since clearance
      level of 68Ge activity in waste may not exceed 10 Bq/g, as stated by European
      Directive 96/29/EURATOM, our purpose was to reduce 68Ge activity in solution from
      >10 kBq/g to <10 Bq/g; which implies the solution can be discarded as regular
      waste. Most efficient method to reduce the 68Ge activity is by sorption of TiO2
      or Fe2O3 and subsequent centrifugation. The required 10 Bq per mL level of 68Ge
      activity in waste was reached by Fe2O3 logarithmically, whereas with TiO2
      asymptotically. The procedure with Fe2O3 eliminates >=90% of the 68Ge activity
      per treatment. Eventually, to simplify the processing a recirculation system was
      used to investigate 68Ge activity sorption on TiO2, Fe2O3 or Zeolite. Zeolite was
      introduced for its high sorption at low pH, therefore 68Ge activity containing
      waste could directly be used without further interventions. 68Ge activity
      containing liquid waste at different HCl concentrations (0.05-1.0 M HCl), was
      recirculated at 1 mL/min. With Zeolite in the recirculation system, 68Ge activity
      showed highest sorption.

PMID- 26224909
TI  - Radiolytic decomposition of pesticide carbendazim in waters and wastes for
      environmental protection.
AB  - The radiolytic degradation of widely used fungicide, carbendazim, in synthetic
      aqueous solutions and industrial wastewater was investigated employing gamma
      irradiation. The effect of the absorbed dose, initial concentration and pH of
      irradiated solution on the effectiveness of carbendazim decomposition were
      investigated. Decomposition of carbendazim in 100 MUM concentration in synthetic
      aqueous solutions required irradiation with 600 Gy dose. The aqueous solutions of
      carbendazim have been irradiated in different conditions, where particular active
      radical species from water radiolysis predominate. The obtained data have been
      compared with the kinetic modeling. The reversed-phase high-performance liquid
      chromatography was used for the determination of carbendazim and its radiolytic
      decomposition products in irradiated solutions. The changes of toxicity of
      irradiated solutions were examined with different test organisms and human
      leukemia cells.

PMID- 26224910
TI  - The comparison of four neutron sources for Prompt Gamma Neutron Activation
      Analysis (PGNAA) in vivo detections of boron.
AB  - A Prompt Gamma Ray Neutron Activation Analysis (PGNAA) system, incorporating an
      isotopic neutron source has been simulated using the MCNPX Monte Carlo code. In
      order to improve the signal to noise ratio different collimators and a filter
      were placed between the neutron source and the object. The effect of the
      positioning of the neutron beam and the detector relative to the object has been
      studied. In this work the optimisation procedure is demonstrated for boron. Monte
      Carlo calculations were carried out to compare the performance of the proposed
      PGNAA system using four different neutron sources (241Am/Be, 252Cf, 241Am/B, and
      DT neutron generator). Among the different systems the 252Cf neutron based PGNAA
      system has the best performance.

PMID- 26224911
TI  - Opportunities for innovation in neutron activation analysis.
AB  - Neutron activation laboratories worldwide are at a turning point at which new
      staff has to be found for the retiring pioneers from the 1960s-1970s. A
      scientific career in a well-understood technique, often characterized as 'mature'
      may only be attractive to young scientists if still challenges for further
      improvement and inspiring new applications can be offered. The strengths and
      weaknesses of neutron activation analysis (NAA) are revisited to identify
      opportunities for innovation. Position-sensitive detection of elements in large
      samples, Monte Carlo calculations replacing the use of standards, use of
      scintillator detectors and new deconvolution techniques for increasing the
      sensitivity are examples of challenging new roads in NAA. Material science
      provides challenges for the application of NAA in both bulk samples, ultrathin
      layers and ultrapure materials.

PMID- 26224912
TI  - Performance and robustness of a multi-user, multi-spectrometer system for INAA.
AB  - The laboratory for instrumental neutron activation analysis at the Reactor
      Institute Delft, Delft University of Technology uses a network of 3 gamma-ray
      spectrometers with well-type detectors and 2 gamma-ray spectrometers with coaxial
      detectors, all equipped with modern sample changers, as well as 2 spectrometers
      with coaxial detectors at the two fast rabbit systems. A wide variety of samples
      is processed through the system, all at specific optimized (and thus different)
      analytical protocols, and using different combination of the spectrometer
      systems. The gamma-ray spectra are analyzed by several qualified operators. The
      laboratory therefore needs to anticipate on the occurrence of random and
      systematic inconsistencies in the results (such as bias, non-linearity or wrong
      assignments due to spectral interferences) resulting from differences in operator
      performance, selection of analytical protocol and experimental conditions. This
      has been accomplished by taking advantage of the systematic processing of
      internal quality control samples such as certified reference materials and blanks
      in each test run. The data from these internal quality control analyses have been
      stored in a databank since 1991, and are now used to assess the various method
      performance indicators as indicators for the method's robustness.

PMID- 26224913
TI  - Trendwatcher or trendsetter; 50 years of MTAA.
AB  - The development on neutron activation analysis (NAA) into a technique of
      practical interest effectively started about 60 years ago, when nuclear reactors
      became available and widely accessible as intense sources of neutrons. During 50
      out these 60 years, the series of Modern Trends in Activation Analysis (MTAA)
      Conferences acted as a true companion and facilitator of this growth. As
      trendwatcher they signalized the many initiatives that contributed to the
      development of activation analysis and its applications. A period has come to an
      end of impressive development resulting from sometimes revolutionary changes in
      radiation detection and data processing, and much improved irradiation
      facilities, NAA has reached a full stage of development, with emphasis on routine
      application and with remaining developments of in marginal impact. NAA is being
      challenged increasingly in the last 30 years by alternative techniques for multi
      trace element analysis. The MTAA Conference and with it the ICAA, the
      International Committee on Activation Analysis, can play an important and active
      role in this process of identifying and selecting key areas, and even promoting
      concerted action in those areas. Such an evolution of focus from retrospective to
      prospective, from trendwatcher to trendsetter, may well allow the MTAA Conference
      to continue and even expand its role in future development of NAA and its
      applications. The ideas about the future of the MTAA Conferences and its
      organization are elaborated upon and some possible subjects for focused
      development activities are indicated.

PMID- 26224914
TI  - Photoneutrons from a beryllium reflector: a potential source of problems with Zr
      Au flux monitors in k0 standardization based neutron activation analysis.
AB  - The assumption that the shape of the epithermal neutron spectrum can be
      described, in any research reactor, by the 1/E1+alpha function is a fundamental
      starting point of the k0 standardization. This assumption may be questioned from
      a reactor physics viewpoint. The type of moderator, the existence of neutron
      reflectors, the additional production of (gamma, n) neutrons and resonance
      capture by construction materials may be different for each reactor, with
      consequences for the shape of the neutron spectrum. This dependency may explain
      that various practitioners reported contradicting experiences with the use of Zr
      Au flux monitors for the determination of the alpha-parameter. An objective view
      on the influence of the design of the reactor and irradiation facility on the
      shape of the neutron spectrum can be obtained by modeling. This has been applied
      in the Reactor Institute Delft for reactor configurations in which the
      irradiation facilities face the fuel elements with the presence of beryllium
      reflector elements. The Monte Carlo calculations indicate a distortion of the
      1/E1+alpha relationship at the higher energy edge of the epithermal neutron
      spectrum. This distortion is attributed to the formation and thermalisation of
      both photoneutrons and (n, 2n) produced fast neutrons in the beryllium, and has a
      direct impact on the resonance activation of 95Zr, other than represented by the
      1/E1+alpha function. The obtained relationship between neutron flux and neutron
      energy was also used for estimating the f-value and compared with the value
      obtained by the Delft Cr-Mo-Au flux monitor.

PMID- 26224915
TI  - TRLFS study on the speciation of uranium in seepage water and pore water of heavy
      metal contaminated soil.
AB  - In situ leaching of uranium ores with sulfuric acid during active uranium mining
      activity on the Gessenheap has caused longstanding environmental problems of acid
      mine drainage and elevated concentrations of uranium. To study there remediation
      measures the test site Gessenwiese, a recultivated former uranium mining heap
      near Ronnenburg/East Thuringia/Germany, was installed as a part of a research
      program of the Friedrich-Schiller University Jena to study, among other
      techniques, the phytoremediation capacity of native and selected plants towards
      uranium. In the first step the uranium speciation in surface seepage and soil
      pore waters from Gessenwiese, ranging in pH from 3.2 to 4.0, were studied by time
      resolved laser-induced fluorescence spectroscopy (TRLFS). Both types of water
      samples showed mono-exponential luminescence decay, indicating the presence of
      only one major species. The detected emission bands were found at 477.5, 491.8,
      513.0, 537.2, 562.3, and 590.7 nm in case of the surface water samples, and were
      found at 477.2, 493.2, 513.8, 537.0, 562.4, and 590.0 nm in case of the soil
      water samples. These characteristic peak maxima together with the observed mono
      exponential decay indicated that the uranium speciation in the seepage and soil
      pore waters is dominated by the uranium (VI) sulfate species UO2SO4(aq). Due to
      the presence of luminescence quenchers in the natural water samples the measured
      luminescence lifetimes of the UO2SO4(aq) species of 1.0-2.6 MUs were reduced in
      comparison to pure uranium sulfate solutions, which show a luminescence lifetime
      of 4.7 MUs. These results convincingly show that in the pH range of 3.2-4.0 TRLFS
      is a suitable and very useful technique to study the uranium speciation in
      naturally occurring water samples.

PMID- 26224916
TI  - Treatment of phosphogypsum waste using suitable organic extractants.
AB  - Phosphogypsum (PG) is a residue of the phosphate fertilizer industry that has
      relatively high concentrations of harmful radioactive materials. The reduction in
      concentration of the radionuclides from PG was investigated. The removal process
      is based on leaching of radionuclides using suitable organic extractants. The
      studied radionuclides were 226Ra, 210Pb, 238U and 40K. The factors affect the
      leaching process such as type of leaching materials, contact time, concentration
      of the desired solvent, liquid to solid ratio, and temperature were studied.
      Based on the experimental results, about 71.1, 76.4, 62.4, and 75.7% of 226Ra,
      210Pb, 238U and 40K respectively were successfully removed from the PG. The
      reduction in the concentration of radionuclides was accompanied by reduction in
      the concentration of rare earth elements (?REE) equals to 69.8%. Using the
      desired organic extractant under optimum conditions for treatment of the PG waste
      leads to obtain a decontaminated product that can be safely used in many
      industrial applications.

PMID- 26224917
TI  - Natural radioactivity in rocks of the Modane-Aussois region (SE France).
AB  - The activity concentrations of 40K, 232Th, and 238U in the characteristic rocks
      of the Modane-Aussois region (Western Alps, France) were determined using an HPGe
      gamma-ray spectrometry system. The activity concentrations of 40K varied from 18
      Bqkg-1 (limestone dolomite) to 392 Bqkg-1 (calcschist), while those of 232Th
      varied from 0.7 Bqkg-1 (limestone dolomite) to 18 Bqkg-1 (calcschist). The
      activities associated with 238U ranged from 9 (quartzite) to 29 Bqkg-1
      (dolomite). In the investigated rock samples, concentrations of 238U (ppm) and
      40K (%) had a strong negative correlation.

PMID- 26224918
TI  - Seasonal changes of 137Cs in benthic plants from the southern Baltic Sea.
AB  - 137Cs activity concentrations were determined in samples of macrophytes
      Polysiphonia fucoides (red algae) and Zostera marina (vascular plant) collected
      during the entire vegetation season in the Gulf of Gdansk in the southern Baltic
      Sea. The measurements showed considerable seasonality of 137Cs activity in both
      species; an increase of cesium concentrations was observed from spring to autumn
      with maximal levels 49.1 +/- 1.4 Bq kgd.w.-1 (P. fucoides) and 14.5 +/- 1.0 Bq
      kgd.w.-1 (Z. marina) in late autumn. 137Cs concentrations observed in a given
      season are the result of a number of processes, the intensity of which can differ
      depending on external environmental conditions. The effects of these processes
      can differ and their directions can frequently be opposite to one another. The
      examined macrophytobenthic plant species could serve as bioindicators of
      radionuclide pollution for monitoring purposes on condition that the samples of
      plants are taken within a strictly defined period of the year to give comparable
      results and to supply realistic information about pollution levels.

PMID- 26224919
TI  - Quantum-mechanical equilibrium isotopic fractionation correction to radiocarbon
      dating: a theory study.
AB  - This paper relates the quantum-mechanical equilibrium isotopic fractionation
      correction to the radiocarbon dating method by Eq. 9, and also shows the
      significant influence of temperature on the method. It is suggested that the
      correction is a function of the frequencies and temperature of a specific sample
      and these two variables can be evaluated theoretically by the ab initio quantum
      calculations and experimentally by analyzing the clumped-isotope ratios in it,
      respectively. This paper also suggests that the 14C/12C ratio in the atmosphere
      in geological time can be calculated by Eq. 10.

PMID- 26224920
TI  - Gamma background measurements in the Laboratoire Souterrain de Modane.
AB  - In situ gamma-ray measurements were taken at six locations in the Modane
      Underground Laboratory. Count rates for gamma radiation within the energy range
      of 7-2734 keV varied from 15 to 108 gammas-1. The arithmetic mean was 79 gammas-1
      for measurements taken without a collimator. The metamorphic rocks surrounding
      the Lab are characterized by low activity concentrations of uranium and thorium
      equal to 12 and 10 Bq kg-1, respectively.

PMID- 26224921
TI  - Biosorption of uranium(VI) by a mangrove endophytic fungus Fusarium sp. #ZZF51
      from the South China Sea.
AB  - The uranium(VI) accumulation was studied in detail by using the biomass of
      mangrove endophytic fungus Fusarium sp.#ZZF51 from the South China Sea. The
      uranium(VI) biosorption process onto the tested fungus powders was optimized at
      pH 4.0, adsorption time 60 min, and uranium(VI) initial concentration 50 mg L-1
      with 61.89% of removal efficiency. According to Fourier transform infrared
      spectra for the tested fungus before and after loaded with uranium(VI), the
      results showed that both of hydroxyl and carboxyl groups acted as the important
      roles in the adsorption process. In addition, the experimental data were analyzed
      by using parameter and kinetic models, and it was obtained that the Langmuir
      isotherm model and the pseudo-second-order kinetic model provided better
      correlation with the experimental data for adsorption of uranium(VI).

PMID- 26224922
TI  - Uranium isotopes as a tracer of groundwater transport studies.
AB  - The activity concentrations of 234U and 238U in thermal groundwater, deep well
      water and river water samples from Central Poland were determined. Concentration
      of 234U and 238U in the examined waters varied from <0.013 (LLD) to 16.8 mBq/dm3
      and from <0.013 (LLD) to 45.5 mBq/dm3 respectively. The highest uranium activity
      concentrations were measured in the thermal groundwater from Mszczonow and
      Cieplice, while the lowest were observed in thermal ground water from Uniejow and
      Poddebice. In thermal groundwater from Skierniewice, uranium activity
      concentrations were below lower limit of detection (0.013 mBq/dm3). The 234U/238U
      activity ratio varied from 0.37 (Cieplice) to 1.30 (Poddebice well water).

PMID- 26224923
TI  - Thermal and X-ray diffraction analysis studies during the decomposition of
      ammonium uranyl nitrate.
AB  - Two types of ammonium uranyl nitrate (NH4)2UO2(NO3)4.2H2O and NH4UO2(NO3)3, were
      thermally decomposed and reduced in a TG-DTA unit in nitrogen, air, and hydrogen
      atmospheres. Various intermediate phases produced by the thermal decomposition
      and reduction process were investigated by an X-ray diffraction analysis and a
      TG/DTA analysis. Both (NH4)2UO2(NO3)4.2H2O and NH4UO2(NO3)3 decomposed to
      amorphous UO3 regardless of the atmosphere used. The amorphous UO3 from
      (NH4)2UO2(NO3)4.2H2O was crystallized to gamma-UO3 regardless of the atmosphere
      used without a change in weight. The amorphous UO3 obtained from decomposition of
      NH4UO2(NO3)3 was crystallized to alpha-UO3 under a nitrogen and air atmosphere,
      and to beta-UO3 under a hydrogen atmosphere without a change in weight. Under
      each atmosphere, the reaction paths of (NH4)2UO2(NO3)4.2H2O and NH4UO2(NO3)3 were
      as follows: under a nitrogen atmosphere: (NH4)2UO2(NO3)4.2H2O ->
      (NH4)2UO2(NO3)4.H2O -> (NH4)2UO2(NO3)4 -> NH4UO2(NO3)3 -> A-UO3 -> gamma-UO3 ->
      U3O8, NH4UO2(NO3)3 -> A-UO3 -> alpha-UO3 -> U3O8; under an air atmosphere:
      (NH4)2UO2(NO3)4.2H2O -> (NH4)2UO2(NO3)4.H2O -> (NH4)2UO2(NO3)4 -> NH4UO2(NO3)3 ->
      A-UO3 -> gamma-UO3 -> U3O8, NH4UO2(NO3)3 -> A-UO3 -> alpha-UO3 -> U3O8; and under
      a hydrogen atmosphere: (NH4)2UO2(NO3)4.2H2O -> (NH4)2UO2(NO3)4.H2O ->
      (NH4)2UO2(NO3)4 -> NH4UO2(NO3)3 -> A-UO3 -> gamma-UO3 -> alpha-U3O8 -> UO2, NH4
      UO2(NO3)3 -> A-UO3 -> beta-UO3 -> alpha-U3O8 -> UO2.

PMID- 26224924
TI  - Determination of the mean aerosol residence times in the atmosphere and
      additional 210Po input on the base of simultaneous determination of 7Be, 22Na,
      210Pb, 210Bi and 210Po in urban air.
AB  - The significant differences in the activities of 210Pb, 210Bi, 210Po and
      cosmogenic 7Be and 22Na radionuclides in the urban aerosol samples collected in
      the summers 2010 and 2011 in the Lodz city of Poland were observed. Simultaneous
      measurement of these radionuclides, after a simple modification of the one
      compartment model, allows us to calculate both: the corrected aerosol residence
      times in the troposphere (1 / 25 days) and in the lower stratosphere (103 / 205
      days). The relative input of the additional sources (beside of the 222Rn decay in
      the air) to the total activity concentrations of 210Pb, 210Bi and 210Po
      radionuclides in the urban air, plays a substantial role (up to 97% of the total
      activity) only in the case of 210Po.

PMID- 26224925
TI  - Distribution of 137Cs in benthic plants along depth profiles in the outer Puck
      Bay (Baltic Sea).
AB  - A study was conducted on three macroalgae species: Polysiphonia fucoides and
      Furcellaria lumbricalis, the species of the red algae division, and Cladophora
      glomerata, representing the green algae division, as well as Zostera marina,
      representing vascular plants. The main aim of the study was to recognize the
      level of 137Cs concentrations in the plants, which could be used as a measurement
      of bioaccumulation efficiency in the selected macrophytes at varying depths, and
      in the seasonal resolution of the vegetation period: spring-summer and autumnal.
      The plants' biomass clearly showed seasonal variability, as did the 137Cs
      concentrations in the plants. Cesium activity also changed with depth. Seasonal
      variability in radionuclide content in the plants, as well as the differences in
      its activity determined along the depth profile, were related mainly to the plant
      biomass and the dilution effect caused by the biomass increment and reflected the
      growth dynamics. P. fucoides showed much greater bioaccumulation ability at each
      depth as compared to C. glomerata, a green algae. Lower concentrations of 137Cs
      were also identified in F. lumbricalis and in Z. marina, mostly as a result of
      differences in morphology and physiology. P. fucoides can be recommended as a
      bioindicator for the monitoring of 137Cs contamination due to the high efficiency
      of bioaccumulation and the available biomass along the depth profile, as well as
      the occurrence throughout the entire vegetation season.

PMID- 26224926
TI  - On variations of volumetric activity of 90Sr and 137Cs in the Baltic Sea coastal
      waters near the shore of Lithuania in 2005-2009.
AB  - The article presents the measurement results of the volumetric activity (VA) of
      artificial radionuclides 90Sr and 137Cs in the coastal waters of the Baltic Sea
      near the Curonian Peninsula in 2005-2009. The annual average values for this
      period of time were 12 Bq/m3 (90Sr) and 40 Bq/m3 (137Cs). Considerable variations
      in the VA of the radionuclide in individual measurements compared to the average
      results were observed. The extreme values were 6 and 16 Bq/m3 for 90Sr and for
      137Cs-27 and 75 Bq/m3. It is proposed to allow such variations under the
      influence of a variety of external factors such as hydro meteorological
      situations, inflowing rivers and bays, storm activity and etc. Besides, a
      possibility of penetration of radionuclides into the sea waters from the
      additional radioactive sources is not excluded.

PMID- 26224927
TI  - Solid-phase extraction of plutonium in various oxidation states from simulated
      groundwater using N-benzoylphenylhydroxylamine.
AB  - Solid-phase extraction of plutonium in different individual and mixed oxidation
      states from simulated groundwater (pH 8.5) was studied. The extraction of
      plutonium species was carried out in a dynamic mode using DIAPAK C16 cartridges
      modified by N-benzoylphenylhydroxylamine (BPHA). It was shown that the extent of
      recovery depends on the oxidation state of plutonium. The extraction of Pu(IV)
      was at the level of 98-99% regardless of the volume and flow-rate of the sample
      solution. Pu(V) was extracted by 90-95% and 75-80% from 10- and 100-mL aliquots
      of the samples, respectively, whereas the extraction of Pu(VI) did not exceed 45
      50%. An equimolar mixture of Pu(IV), Pu(V), and Pu(VI) was extracted by 74%. The
      distribution coefficients (Kd) and kinetic exchange capacities (S) of plutonium
      in various oxidation states were measured. It was found that during the sorption
      process, Pu(V) was reduced to Pu(IV) by 80-90% after an hour-long contact with
      the solid phase. Pu(VI) is reduced to Pu(V) by 34% and to Pu(IV) by 55%. In the
      case of mixed-valent solution of plutonium, only Pu(V) and Pu(IV) were found in
      the effluents.

PMID- 26224928
TI  - Search of ligands suitable for 212Pb/212Bi in vivo generators.
AB  - The short half-life of 212Bi and 213Bi limits the application of these
      radionuclides in alpha radionuclide therapy. The labeling of biomolecules with
      212Pb (mother nuclide of 212Bi) instead of 212Bi or 213Bi has the advantage of
      obtaining a conjugate with a half-life of 10.6 h, compared with of 60 min for
      212Bi or 46 min for 213Bi. Previous attempts to prepare a potential in vivo
      generator with 212Pb complexed by the DOTA chelator failed, because about 36 % of
      Bi was reported to escape as a result of the radioactive decay [Formula: see
      text]. Herein, we report studies on the stability of the 212Pb complexes with
      eight selected polydentate ligands, which demonstrate high affinity for 3+ metal
      cations. From the ligand studied DOTP and BAPTA show a sufficient 212Pb labeling
      yields but only 212Pb-DOTP complex is stable in isotonic solution of sodium
      chloride making this way radioactivity level of released 212Bi is below the limit
      of detection. It should be emphasized that the DOTP complex is stable only in the
      case when the concentration of free DOTP exceeds 10-4 M.

PMID- 26224929
TI  - Gamma background measurements in the Gran Sasso National Laboratory.
AB  - In situ gamma-ray measurements were taken at eight locations in the Gran Sasso
      National Laboratory (Italy). Count rates for gamma radiation within the energy
      range of 7-2,734 keV varied from 8 to 60 gamma s-1. The arithmetic mean was 49
      gamma s-1 for measurements taken without a collimator. The average gamma flux
      inside the Lab was 0.25 gamma cm-2 s-1. The sedimentary rocks surrounding the Lab
      are characterized by low activity concentrations of uranium and thorium, equal to
      1.7 and 1.4 Bq kg-1, respectively.

PMID- 26224930
TI  - A preliminary study on 226Ra, 232Th, 40K and 137Cs activity concentrations in
      vegetables and fruits frequently consumed by inhabitants of Elazig Region,
      Turkey.
AB  - Determining radioactivity levels in foodstuffs is of great importance for the
      protection of human health. In addition, the literature includes few studies
      related to this subject in Turkey. In this study, gamma spectroscopic system was
      used in order to measure 226Ra, 232Th, 40K and 137Cs activity concentrations in
      vegetables and fruits produced in Elazig Region. The average activity
      concentrations in vegetables was calculated as 0.64 +/- 0.26 Bq kg-1 for 226Ra,
      0.65 +/- 0.14 Bq kg-1 for 232Th, 13.98 +/- 1.22 Bq kg-1 for 40K, and 0.54 +/-
      0.04 Bq kg-1 for 137Cs. The average activity concentrations in fruits were 1.52
      +/- 0.34, 0.98 +/- 0.23, 18.66 +/- 1.13 and 0.59 +/- 0.16 Bq kg-1, respectively
      for 226Ra, 232Th, 40K and 137Cs. Total committed effective dose value was
      determined as 20 and 30.55 MUSv y-1, respectively for vegetables and fruits. The
      findings were compared with previous data reported for Turkey and other regions
      of the world.

PMID- 26224931
TI  - Synthesis of multidentate ligands with amido or amino donor groups for the
      preparation of rhenium and technetium radiopharmaceuticals.
AB  - A new method to prepare novel semi-rigid multidentate ligands containing nitrogen
      atom, to coordinate with rhenium and technetium, was established. The method was
      based on formylation of substituted anilines, followed by Mannich reaction with
      glycine and paraformaldehyde. The method was very promising to design ligands of
      various molecular structures (L1-L5) to coordinate with rhenium metal ions. The
      complexes were prepared through ligand exchange with the complex ReOCl3(PPh3)2,
      giving new complex of the structure ReOCl3L(1-5). The prepared ligands and
      complexes were identified by the use of UV-vis, and infrared absorption
      spectrometric techniques, elemental analysis, molecular weight determination by
      depression of freezing point. These ligands were labeled with 99mTc
      pertechnetate, and the labeling efficiency of the complexes was measured using a
      well type scintillation gamma counter equipment and obtained a good yield.

PMID- 26224932
TI  - Stability of 47Sc-complexes with acyclic polyamino-polycarboxylate ligands.
AB  - The aim of this study was to evaluate acyclic ligands which can be applied for
      labeling proteins such as monoclonal antibodies and their fragments with scandium
      radionuclides. Recently, scandium isotopes (47Sc, 44Sc) are more available and
      their properties are convenient for radiotherapy or PET imaging. They can be used
      together as "matched pair" in theranostic approach. Because proteins denaturize
      at temperature above 42  degrees C, ligands which efficiently form complexes at
      room temperature, are necessary for labelling such biomolecules. For complexation
      of scandium radionuclides open chain ligands DTPA, HBED, BAPTA, EGTA, TTHA and
      deferoxamine have been chosen. We found that the ligands studied (except HBED)
      form strong complexes within 10 min and that the radiolabelling yield varies
      between 96 and 99 %. The complexes were stable in isotonic NaCl, but stability of
      46Sc-TTHA, 46Sc-BAPTA and 46Sc-HBED in PBS buffer was low, due to formation by
      Sc3+stronger complexes with phosphates than with the studied ligands. From the
      radiolabelling studies with n.c.a. 47Sc we can conclude that the most stable
      complexes are formed by the 8-dentate DTPA and EGTA ligands.

PMID- 26224933
TI  - Radon concentrations in kindergartens and schools in two cities: Kalisz and
      Ostrow Wielkopolski in Poland.
AB  - Plastic PicoRad detectors with activated charcoal have been used for radon
      monitoring in local kindergartens and schools in two cities, Kalisz and Ostrow
      Wielkopolski, in the region of Greater Poland. Detectors were exposed for a
      standard time of 48 h during the autumn and winter of 2011 in 103 rooms (Kalisz)
      and 55 rooms (Ostrow Wlkp), respectively. The detectors were calibrated in the
      certified radon chamber of the Central Laboratory for Radiological Protection in
      Warsaw, Poland. The arithmetic and geometric means of indoor radon concentrations
      in the examined rooms were 46.0 and 30.3 Bq/m3 for Kalisz and 48.9 and 29.8 Bq/m3
      for Ostrow Wlkp, respectively. The measured levels of the indoor radon
      concentrations were relatively low, since the main source of indoor radon for
      these low storey (max. three storeys) buildings is radon escaping from the
      underlying soil with a low 226Ra concentration (~15 Bq/m3). Therefore, the
      calculated annual effective doses from that source for the children in Kalisz and
      Ostrow Wlkp were also low 0.35 mSv.

PMID- 26224934
TI  - 226Ra, 210Pb, 210Bi and 210Po deposition and removal from surfaces and liquids.
AB  - Deposition of 226Ra from water on nylon was investigated. Measurements performed
      for different pH and different radium concentrations in the water gave similar
      absolute activities deposited on the foil surface. Obtained results were used to
      estimate the amount of 226Ra plated-out on the nylon scintillator vessel in the
      solar neutrino experiment BOREXINO during filling of the detector. Another
      problem studied in the frame of BOREXINO was the removal of 210Pb from its
      organic liquid scintillator by applying distillation and water extraction. After
      several tests had been performed for both methods it was found that after the
      water extraction the initial lead content in the scintillator sample was reduced
      only accordingly to the ratio of the volumes of the applied liquids (simple
      dilution). In contrast to this, distillation was very effective providing in the
      best case a 210Pb reduction factor higher than 100. Removal efficiencies of the
      long-lived 222Rn daughters during etching from surfaces of standard and high
      purity germanium were investigated in the frame of the GERDA experiment, which
      aims to search for neutrino-less double beta decay of 76Ge. The standard etching
      procedure of Canberra used during production of high purity n-type germanium
      diodes was applied to germanium discs, which had been exposed earlier to a strong
      222Rn source for its progenies deposition. In contrast to copper and stainless
      steel, 210Pb, 210Bi and 210Po was removed from germanium very efficiently. An
      evidence of a reverse process was also observed-the isotopes were transferred
      from the etchant to the clean germanium surface.

PMID- 26224935
TI  - New approaches to reprocessing of oxide nuclear fuel.
AB  - Dissolution of UO2, U3O8, and solid solutions of actinides in UO2 in subacid
      aqueous solutions (pH 0.9-1.4) of Fe(III) nitrate was studied. Complete
      dissolution of the oxides is attained at a molar ratio of ferric nitrate to
      uranium of 1.6. During this process actinides pass into the solution in the form
      of U(VI), Np(V), Pu(III), and Am(III). In the solutions obtained U(VI) is stable
      both at room temperature and at elevated temperatures (60  degrees C), and at
      high U concentrations (up to 300 mg mL-1). Behavior of fission products
      corresponding to spent nuclear fuel of a WWER-1000 reactor in the process of
      dissolution the simulated spent nuclear fuel in ferric nitrate solutions was
      studied. Cs, Sr, Ba, Y, La, and Ce together with U pass quantitatively from the
      fuel into the solution, whereas Mo, Tc, and Ru remain in the resulting insoluble
      precipitate of basic Fe salt and do not pass into the solution. Nd, Zr, and Pd
      pass into the solution by approximately 50 %. The recovery of U or jointly U + Pu
      from the dissolution solution of the oxide nuclear fuel is performed by
      precipitation of their peroxides, which allows efficient separation of actinides
      from residues of fission products and iron.

PMID- 26224936
TI  - Evaluation of a new radiolabeled bombesin derivative with 99mTc as potential
      targeted tumor imaging agent.
AB  - Gastrin-releasing peptide (GRP) receptors are over-expressed in various human
      tumor including breast and prostate which can be targeted with bombesin for
      diagnosis and targeted therapy. High abdominal accumulation and the poor in vivo
      stability of radiolabeled bombesin analogues may represent a limitation for
      diagnostic imaging and targeted therapy. In this study a new bombesin derivative
      was labeled with 99mTc via HYNIC and tricine as a coligand and investigated
      further. The peptide HYNIC conjugate was synthesized on a solid phase using Fmoc
      strategy. Labeling with 99mTc was performed at 100  degrees C for 10 min and
      radiochemical analysis involved ITLC and HPLC methods. The stability of
      radiopeptide was checked in the presence of human serum at 37  degrees C up to 24
      h. Internalization was studied with the human GRP receptor cell line PC-3. The
      Biodistribution was studied in mice. Labeling yield of >98 % was obtained to
      correspond a specific activity of ~80.9 GBq/MUmol. Radioconjugate internalization
      into PC-3 cells was high and specific (15.6 +/- 1.9 % at 4 h). A high and
      specific uptake in GRP-receptor-positive organs such as mouse tumor and pancreas
      (2.11 +/- 0.18 and 1.78 +/- 0.09 % ID/g after 1 h respectively) was also
      determined.

PMID- 26224937
TI  - A purification system for 64Cu produced by a biomedical cyclotron for antibody
      PET imaging.
AB  - Ion exchange is a simple and efficient method for separating no-carrier-added
      64Cu from an irradiated Ni target. We developed a semi-automated two-round 64Cu
      separation system equipped with a strong-base anion exchange resin column. We
      first verified the efficiency of the system using a non-radioactive substitute
      consisting of 25 mg of Ni and 127 ng of Cu, and confirmed that Cu was completely
      eluted at the second round of the separation step. After the bombardment,
      separation of 64Cu from the Ni target was achieved with high radiochemical
      purity. 64Cu produced and separated in this study had an extremely low level of
      Ni impurity. It could be used for labeling monoclonal antibodies for antibody
      positron emission tomography imaging and synthesizing radiopharmaceuticals.

PMID- 26224938
TI  - Extraction of the 131Cs from neutron irradiated barium oxide under microwave
      radiation.
AB  - In this work, the solubility dependence of radioactive baric samples under
      influence of microwave radiation (MWR) has been investigated at various
      concentrations of HCl after irradiation of BaO target at a flux of thermal
      neutrons. It is established that the use of MWR for dissolution of a sparingly
      soluble barium oxide will accelerate a dissolution process at almost an order of
      magnitude in comparison with usual heating. Each time after separation of the
      131Cs from radioactive barium solution analyses on radionuclide purity of the
      131Cs product solutions were carried out.

PMID- 26224939
TI  - Fast procedure for self-absorption correction for low gamma energy radionuclide
      210Pb determination in solid environmental samples.
AB  - Low-energy X and gamma radiations (for example of 210Pb: Egamma = 46.5 keV) are
      effectively self-absorbed even in thin environmental samples, including air
      filters with captured dust or contaminated soil, as well as in bottom sediment
      matrixes with limited quantities of the samples. In this paper, a simple method
      for the direct analysis of 210Pb (T1/2 = 22.3 years) by gamma-ray spectrometry in
      environmental samples with self-absorption correction is described. The method is
      based on the comparison of two gamma peak activities coming from other natural
      radionuclides, usually present in environmental samples. We have analyzed the
      dependence of the self-absorption correction factor for the 210Pb activity on the
      activity ratios of 911 and 209 keV peaks and 609 and 295 keV peaks coming from
      nuclides of 238U or 232Th rows, present in typical environmental samples.

PMID- 26224940
TI  - Accelerator mass spectrometry (AMS) in plutonium analysis.
AB  - The paper summarizes the results of the 240Pu/239Pu atomic ratio studies in
      atmospheric fallout samples collected in 1986 over Gdynia (Poland) as well as
      three Baltic fish species collected in 1997 using the accelerator mass
      spectrometry. A new generation of AMS has been developed during last years and
      this method is an efficient and good technique to measure long-lived
      radioisotopes in the environment and provides the most accurate determination of
      the atomic ratios between 240Pu and 239Pu. The nuclide compositions of plutonium
      in filter samples correspond to their means of production. AMS measurements of
      atmospheric fallout collected in April showed sufficient increase of the
      240Pu/239Pu atomic ratio from 0.28 from March to 0.47. Also such high increase of
      240Pu/239Pu atomic ratio, close to reactor core 240Pu/239Pu atomic ratio, was
      observed in September and equaled 0.47.

PMID- 26224941
TI  - A novel approach towards development of real time chemical dosimetry using
      pulsating sensor-based instrumentation.
AB  - The paper presents an innovative approach towards development of real time
      dosimetry using a chemical dosimeter for measurement of absorbed radiation dose
      in the range between 1 and 400 Gy. Saturated chloroform solution in water, a well
      known chemical dosimeter, is used to demonstrate the concept of online
      measurement of radiation dose. The measurement approach involves online
      monitoring of increase in conductivity of saturated chloroform solution due to
      progressive build up of traces of highly conducting HCl during exposure to gamma
      irradiation. A high performance pulsating sensor-based conductivity monitoring
      instrument has been used to monitor such real time change in conductivity of
      solution. A relation between conductivity shift and radiation dose has been
      established using radiochemical yield value (G value) of HCl. The G value of HCl
      in saturated chloroform dosimeter has been determined using laboratory developed
      pulsating sensor-based devices. In this connection dose rate of Co-60 gamma
      chamber was determined using Fricke dosimeter following a simple potentiometric
      measurement approach developed in-house besides conventional spectrophotometry.
      Results obtained from both measurement approaches agreed well. Complete
      instrumentation package has also been developed to measure real time radiation
      dose. The proposed real time radiation dosimeter is successfully tested in
      several measurement campaigns in order to assure its performance prior to its
      deployment in field.

PMID- 26224942
TI  - Radiation graft post-polymerization of sodium styrene sulfonate onto
      polyethylene.
AB  - Post-irradiation grafting of sodium styrene sulfonate (SSS) in the presence of
      acrylic acid (AA) has been investigated on polyethylene (PE) pre-exposed to gamma
      radiation at room temperature in the air. Special attention was paid to the
      effect of low molecular weight salt additives on the kinetics of graft
      copolymerization of SSS and AA. The presence of SSS links in the grafted PE
      copolymers was detected by the methods of UV and FTIR spectroscopy. Based on the
      FITR spectroscopy and element analysis data, a mechanism was proposed for graft
      copolymerization of SSS and AA onto PE. The mechanical properties of the graft
      copolymers were studied. It was established that PE copolymers grafted with
      sulfonic acid and carboxyl groups have higher strength characteristics (16.3 MPa)
      compared to the samples containing only carboxyl groups (11 MPa).

PMID- 26224943
TI  - Innovative concept for a major breakthrough in atmospheric radioactive xenon
      detection for nuclear explosion monitoring.
AB  - The verification regime of the comprehensive test ban treaty (CTBT) is based on a
      network of three different waveform technologies together with global monitoring
      of aerosols and noble gas in order to detect, locate and identify a nuclear
      weapon explosion down to 1 kt TNT equivalent. In case of a low intensity
      underground or underwater nuclear explosion, it appears that only radioactive
      gases, especially the noble gas which are difficult to contain, will allow
      identification of weak yield nuclear tests. Four radioactive xenon isotopes,
      131mXe, 133mXe, 133Xe and 135Xe, are sufficiently produced in fission reactions
      and exhibit suitable half-lives and radiation emissions to be detected in
      atmosphere at low level far away from the release site. Four different monitoring
      CTBT systems, ARIX, ARSA, SAUNA, and SPALAXTM have been developed in order to
      sample and to measure them with high sensitivity. The latest developed by the
      French Atomic Energy Commission (CEA) is likely to be drastically improved in
      detection sensitivity (especially for the metastable isotopes) through a higher
      sampling rate, when equipped with a new conversion electron (CE)/X-ray
      coincidence spectrometer. This new spectrometer is based on two combined
      detectors, both exhibiting very low radioactive background: a well-type NaI(Tl)
      detector for photon detection surrounding a gas cell equipped with two large
      passivated implanted planar silicon chips for electron detection. It is
      characterized by a low electron energy threshold and a much better energy
      resolution for the CE than those usually measured with the existing CTBT
      equipments. Furthermore, the compact geometry of the spectrometer provides high
      efficiency for X-ray and for CE associated to the decay modes of the four
      relevant radioxenons. The paper focus on the design of this new spectrometer and
      presents spectroscopic performances of a prototype based on recent results
      achieved from both radioactive xenon standards and air sample measurements. Major
      improvements in detection sensitivity have been reached and quantified,
      especially for metastable radioactive isotopes 131mXe and 133mXe with a gain in
      minimum detectable activity (about 2 * 10-3 Bq) relative to current CTBT SPALAXTM
      system (air sampling frequency normalized to 8 h) of about 70 and 30
      respectively.

PMID- 26224944
TI  - Radionuclides and heavy metal concentrations as complementary tools for studying
      the impact of industrialization on the environment.
AB  - The aim of the study was to determine whether using chemical and radiochemical
      analysis of lake sediments can highlight changes in the climate. Also it was
      studied whether human impact on the environment can be observed and to what
      extent such changes are in agreement with historical data. Samples of 16 cm thick
      sediment cores from the Smreczynski Staw Lake were collected and divided into 1
      cm thick sub-samples. The samples were air dried and homogenized. The
      quantitative analysis of Fe, Mn, Zn, Cr, Cu, Ni, Cd, and Pb in the digested
      sediment samples was made by using atomic absorption spectrometry.
      Simultaneously, the radioactivity of 137Cs using gamma spectrometry and 210Pbuns
      using alpha spectrometry, were measured for sediment layer dating. Results showed
      that iron concentration was in the range 0.3-over 1 % (w/w), and zinc 0.01-0.05 %
      (w/w). Lesser concentrations were found for copper 18.37-43.6 ppm, manganese 37.5
      50.7 ppm, lead 146.1-432 ppm, chromium 12.3-37.4 ppm, nickel 3.1-10.8 ppm and
      cadmium 0.9-34.6 ppm. Changes in 137Cs radioactivity was in the range of 89 +/-
      11 to 865 +/- 62 (Bq kg-1). Sediments composition can accurately reflect (in
      terms of time and to what extent) air pollution and natural geo-chemical
      processes in the environment. However, the choice of the analysed object is
      crucial in this respect. The Smreczynski Staw Lake, due to its location in the
      mountains and hydrological situation, proved to be very useful for providing
      undisturbed analytical samples.

PMID- 26224945
TI  - Determination of air-loop volume and radon partition coefficient for measuring
      radon in water sample.
AB  - A simple method for the direct determination of the air-loop volume in a RAD7
      system as well as the radon partition coefficient was developed allowing for an
      accurate measurement of the radon activity in any type of water. The air-loop
      volume may be measured directly using an external radon source and an empty
      bottle with a precisely measured volume. The partition coefficient and activity
      of radon in the water sample may then be determined via the RAD7 using the
      determined air-loop volume. Activity ratios instead of absolute activities were
      used to measure the air-loop volume and the radon partition coefficient. In order
      to verify this approach, we measured the radon partition coefficient in deionized
      water in the temperature range of 10-30  degrees C and compared the values to
      those calculated from the well-known Weigel equation. The results were within 5 %
      variance throughout the temperature range. We also applied the approach for
      measurement of the radon partition coefficient in synthetic saline water (0-75
      ppt salinity) as well as tap water. The radon activity of the tap water sample
      was determined by this method as well as the standard RAD-H2O and BigBottle RAD
      H2O. The results have shown good agreement between this method and the standard
      methods.

PMID- 26224946
TI  - Gamma background measurements in the Boulby Underground Laboratory.
AB  - To determine background radiation levels that might influence experiments, we
      measured in situ gamma-ray emissions at ten locations in the Boulby Underground
      Laboratory. For gamma radiation in the energy range of 7-2,734 keV, the counts
      varied from 6.5 to 28 gamma s-1. For measurements inside the Lab, the arithmetic
      mean was 24 gamma s-1. The sedimentary rocks that surrounded the Lab, halite and
      mudstone, were characterized by very low activity concentrations of uranium (0.8
      7.1 Bq kg-1) and thorium (0.6-3.9 Bq kg-1).

PMID- 26224947
TI  - Separation of fission produced 106Ru from simulated high level nuclear wastes for
      production of brachytherapy sources.
AB  - An effective and simple process for the isolation of 106Ru from high-level liquid
      wastes was developed. Radioactive ruthenium was oxidized by H5IO6 in HNO3
      solution and was extracted to CCl4 phase in the form of RuO4. In order to obtain
      ruthenium in the suitable form for production of brachytherapy sources, RuO4 in
      organic phase was reduced and re-extracted to aqueous phase. The efficiency of
      extraction of 103Ru to organic phase was 86 %, re-extraction to aqueous solution
      was near 100 %, so the overall recovery of 103Ru is estimated at more than 80 %.

PMID- 26224948
TI  - Rapid determination of 237Np in soil samples by multi-collector inductively
      coupled plasma mass spectrometry and gamma spectrometry.
AB  - A radiochemical procedure is developed for the determination of 237Np in soil
      with multi-collector inductively-coupled plasma mass spectrometry (MC-ICP-MS) and
      gamma-spectrometry. 239Np (milked from 243Am) was used as an isotopic tracer for
      chemical yield determination. The neptunium in the soil is separated by thenoyl
      trifluoracetone extraction from 1 M HNO3 solution after reducing Np to Np(IV)
      with ferrous sulfamate, and then purified with Dowex 1 * 2 anion exchange resin.
      239Np in the resulting solution is measured with gamma-spectrometry for chemical
      yield determination while the 237Np is measured with MC-ICP-MS. Measurement
      results for soil samples are presented together with those for two reference
      samples. By comparing the determined value with the reference value of the 237Np
      activity concentration, the feasibility of the procedure was validated.

PMID- 26224949
TI  - Generation of the additional fluorescence radiation in the elastomeric shields
      used in computer tomography (CT).
AB  - Two commercially available (EP, Z) and eight new elastomeric composites (M1-M4,
      G1-G4, of thickness ~1 mm) containing mixtures of differing proportions of heavy
      metal additives (Bi, W, Gd and Sb) have been synthesised and examined as
      protective shields. The intensity of the X-ray fluorescence radiation generated
      in the typical elastomeric shields for CT, containing Bi and other heavy metal
      additives influence on the practical shielding properties. A method for assessing
      the radiation shielding properties of elastomeric composites used in CT
      examination procedures via X-ray spectrometry has been proposed. To measure the
      radiation reduction ability of the protective shields, the dose reduction factor
      (DRF) has been determined. The lead equivalents for the examined composites were
      within the ranges of 0.046-0.128 and 0.048-0.130 mm for 122.1 and 136.5 keV
      photons, respectively. The proposed method, unlike to the common approach,
      includes a dose contribution from the induced X-ray fluorescence radiation of the
      heavy metal elements in the protective shields. The results clearly indicate that
      among the examined compositions, the highest values DRF have been achieved with
      preparations containing Bi+W, Bi+W+Gd and Bi+W+Sb mixtures with gradually
      decreasing content of heavy metal additives in the following order: Bi, W, Gd and
      Sb. The respective values of DRF obtained for the investigated composites were
      21, 28 and 27 % dose reduction for a 1 mm thick shield and 39 and ~50 % for a 2
      mm thick layer (M1-M4).

PMID- 26224950
TI  - A new approach to analysis of relationships between 137Cs activity concentrations
      in forest soil horizons.
AB  - The measurements results of 137Cs activity concentrations in forest soil profiles
      are discussed. In studies some simplifications were considered. First of them
      concerns disregarding of soil subtype in data analysis. However initially this
      parameter was considered in data analysis, it was finally ignored. The second
      assumption drops information about specific soil horizon. Description of 137Cs
      accumulation is based on relationships between its relative activity
      concentrations in soil layers. The model formulation was based on the results of
      exploratory data analysis of the relative 137Cs activity concentrations. In
      studies the methods designed for compositional data analysis were used. The
      results of analysis showed that the relationships between the relative activity
      concentrations of 137Cs in soil layers, due to their nature, might be divided
      into two groups. The first of them concerns layers located close to soil surface.
      The relative activity concentrations of 137Cs in these layers are proportional to
      each other, and distribution mechanism of cesium within them has the
      characteristics of the process leading to thermodynamic equilibrium. The second
      group is related to layers that are located deeper. The calculation results
      suggest lack of thermodynamic equilibrium between these layers and layers
      situated above. Utilization of a linear model for description of changes in
      relative activity concentrations of 137Cs in deeper layers supposes that these
      changes occur much slower than in layers lying above.

PMID- 26224951
TI  - Liquid-liquid extraction of uranium(VI) in the system with a membrane contactor.
AB  - Raising role of the nuclear power industry, including governmental plans for the
      construction of first nuclear power plant in Poland, creates increasing demand
      for the uranium-based nuclear fuels. The project implemented by Institute of
      Nuclear Chemistry and Technology concerns the development of effective methods
      for uranium extraction from low-grade ores and phosphorites for production of
      yellow cake-U3O8. The Liqui-Cel(r) Extra-Flow 2.5 * 8 Membrane Contactor produced
      by CELGARD LLC (Charlotte, NC) company is the main component of the installation
      for liquid-liquid extraction applied for processing of post leaching liquors. In
      the process of membrane extraction the uranyl ions from aqueous phase are
      transported through the membrane into organic phase. The flow of two phases in
      the system was arranged in co-current mode. The very important element of the
      work was a selection of extracting agents appropriate for the membrane process.
      After preliminary experiments comprising tests of membrane resistivity and
      determination of extraction efficiency, di(2-ethylhexyl)phosphoric acid was found
      to be most favourable. An important aspect of the work was the adjustment of
      hydrodynamic conditions in the capillary module. To avoid the membrane
      wettability by organic solvent and mixing two phases equal pressure drops along
      the membrane module to minimize the transmembrane pressure, were assumed.
      Determination of pressure drop along the module was conducted using Bernoulli
      equation. The integrated process of extraction/re-extraction conducted in
      continuous mode with application of two contactors was designed.

PMID- 26224952
TI  - The evaluation of 137Cs radioactivities in soils taken from the Babia Gora
      National Park.
AB  - The aim of this work was to determine 137Cs and 40K radioactivities in soil
      samples taken from the Babia Gora National Park (BPN) in south Poland. The
      cluster analysis (CA) and principal component analysis (PCA) were used to discuss
      the obtained data. 10 cm thick soil cores were collected from the BPN area. Each
      sample was divided into three sub-samples. The samples were dried, homogenized
      and packed in polyethylene containers. The radioactivities of 137Cs and 40K were
      measured by means of gamma spectrometry. It was found that 137Cs radioactivity in
      the whole 10 cm soil cores was in the range from 1,916 to 28,551 Bq m-2. The
      radioactivity of 40K varied from 1,642 to 25,654 Bq m-2. Using CA it was possible
      to diverse the soils taking into account soil types. By use of the PCA method, it
      was chosen three factors which are appropriate to characterize researched
      parameters.

PMID- 26224953
TI  - Study on the rate of plutonium vertical migration in various soil types of Lublin
      region (Eastern Poland).
AB  - Soil contamination level with 239+240Pu of Lublin region was determined using the
      alpha spectrometric method. Results were compared with similar data from the
      study performed 15 year earlier. Decrease in total 239+240Pu concentration and
      reducing quantity of Chernobyl fraction (up to almost negligible value of 1 %)
      has been observed in upper soil layer. Determination of 239+240Pu concentration
      in soil profile layers allows calculating a vertical migration velocity of
      plutonium applying a compartment migration model. It was found that 239+240Pu
      migration rate varies depending on soil type from 0.29 cm year-1 in Podsols to
      0.58 cm year-1 in Fluvisols with mean value of 0.5 cm year-1.

PMID- 26224954
TI  - Synthesis of microspheres of triuranium octaoxide by simultaneous water and
      nitrate extraction from ascorbate-uranyl sols.
AB  - A new method for synthesis of uranium oxide microspheres (diameter <100 MUm) has
      been developed. It is a variant of our patented Complex Sol-Gel Process, which
      has been used to synthesize high-quality powders of a wide variety of complex
      oxides. Starting uranyl-nitrate-ascorbate sols were prepared by addition of
      ascorbic acid to uranyl nitrate hexahydrate solution and alkalizing by aqueous
      ammonium hydroxide and then emulsified in 2-ethylhexanol-1 containing 1v/o SPAN
      80. Drops of emulsion were firstly gelled by extraction of water by the solvent.
      Destruction of the microspheres during thermal treatment, owing to highly
      reactive components in the gels, requires modification of the gelation step by
      Double Extraction Process-simultaneously extraction of water and nitrates using
      Primene JMT, which completely eliminates these problem. Final step was
      calcination in air of obtained microspheres of gels to triuranium octaoxide.

PMID- 26224956
TI  - Target preparation for research with charged projectiles.
AB  - The paper reviews in a compact format the techniques most frequently used for
      target preparation, such as rolling, powder compacting, and vacuum deposition.
      The survey covers also the techniques used for target characterisation
      (thickness, purity) and problems related to the extension of target life-time and
      time of uninterrupted experiments with use of targets.

PMID- 26224955
TI  - Enzymatic synthesis of tryptamine and its halogen derivatives selectively labeled
      with hydrogen isotopes.
AB  - Nine isotopomers of tryptamine and its halogen derivatives, labeled with
      deuterium, tritium in side chain, i.e., [(1R)-2H]-, [(1R)-3H]-, 5-F-[(1R)-2H]-, 5
      F-[(1R)-3H]-, 5-Br-[(1R)-2H]-, double labeled [(1R)-2H/3H]-, 5-F-[(1R)-2H/3H]-,
      and ring labeled [4-2H]-, and [5-2H]-tryptamine, were obtained by enzymatic
      decarboxylation of l-Trp and its appropriate derivatives in deuteriated or
      tritiated media, respectively. Intermediates: [5'-2H]-l-Trp used for further
      decarboxylation was synthesized by enzymatic coupling of [5-2H]-indole with S
      methyl-l-cysteine, and [4'-2H]-l-Trp was obtained by isotope exchange 1H/2H of
      the authentic l-Trp dissolved in heavy water induced by UV-irradiation. Doubly
      labeled [(1R)-2H/3H]- and 5-F-[(1R)-2H/3H]-tryptamine were obtain by
      decarboxylation of l-Trp or [5'-F]-l-Trp carried out in 2H3HO incubation medium.

PMID- 26224957
TI  - Fine plastic foil as backing for sputtered nickel targets.
AB  - Targets of 58Ni and 60Ni with areal density between 71 and 105 MUg/cm2 backed
      with polyimide foil of 35-40 MUg/cm2 were prepared by sputtering with Ar ions
      produced by a home made sputtering device at the Target Laboratory, University of
      Jyvaskyla. The efficiency of the procedure was about 20 %.

PMID- 26224958
TI  - Uranium concentration in blood samples of Southern Iraqi leukemia patients using
      CR-39 track detector.
AB  - The simple and effective technique of fission track etch has been applied to
      determine trace concentration of uranium in human blood samples taken from two
      groups of male and female participants: leukemia patients and healthy subjects
      group. The blood samples of leukemia patients and healthy subjects were collected
      from three key southern governorates namely, Basrah, Muthanna and Dhi-Qar. These
      governorates were the centers of intensive military activities during the 1991
      and 2003 Gulf wars, and the discarded weapons are still lying around in these
      regions. CR-39 track detector was used for registration of induced fission
      tracks. The results show that the highest recorded uranium concentration in the
      blood samples of leukemia patients was 4.71 ppb (female, 45 years old, from
      Basrah) and the minimum concentration was 1.91 ppb (male, 3 years old, from
      Muthanna). For healthy group, the maximum uranium concentration was 2.15 ppb
      (female, 55 years old, from Basrah) and the minimum concentration was 0.86 ppb
      (male, 5 years old, from Dhi-Qar). It has been found that the uranium
      concentrations in human blood samples of leukemia patients are higher than those
      of the healthy group. These uranium concentrations in the leukemia patients group
      were significantly different (P < 0.001) from those in the healthy group.

PMID- 26224959
TI  - Radon (222Rn) in underground drinking water supplies of the Southern Greater
      Poland Region.
AB  - Activity concentration of the 222Rn radionuclide was determined in drinking water
      samples from the Sothern Greater Poland region by liquid scintillation technique.
      The measured values ranged from 0.42 to 10.52 Bq/dm3 with the geometric mean
      value of 1.92 Bq/dm3. The calculated average annual effective doses from
      ingestion with water and inhalation of this radionuclide escaping from water were
      1.15 and 11.8 MUSv, respectively. Therefore, it should be underlined that,
      generally, it's not the ingestion of natural radionuclides with water but
      inhalation of the radon escaping from water which is a substantial part of the
      radiological hazard due to the presence of the natural radionuclides from the
      uranium and thorium series in the drinking water.

PMID- 26224960
TI  - Concentrations of 137Cs and 40K radionuclides and some heavy metals in soil
      samples from the eastern part of the Main Ridge of the Flysch Carpathians.
AB  - The aim of the study is to present the results of determination of radioactivity
      of artificial 137Cs and natural 40K and certain heavy metals in soil samples
      collected from the eastern part of the Main Ridge of Carpathians, including the
      Beskid Niski Mts and the Bieszczady Mts. The evaluation of level of radionuclides
      was based on the bulk density analysis of the soil. A valuable finding of the
      study was a good linear correlation between the level of 137Cs concentration and
      bulk density of the soil as well as an inverse correlation between radioactivity
      of natural 40K and tested soil density. This might indicate though a high
      competitiveness of these elements between each other. Moreover, a good
      correlation between the concentrations of artificial element 137Cs and Pb has
      been also observed in soil samples collected from the Beskid Niski Mts. In most
      cases, the level of artificial 137Cs was lower comparing to an average 137Cs
      concentration established for soils in Poland.

PMID- 26224961
TI  - Studies on enzymatic oxidation of 3',4'-dihydroxy-l-phenylalanine to dopachrome
      using kinetic isotope effect methods.
AB  - We report the studies on the mechanism of oxidation of 3',4'-dihydroxy-l
      phenylalanine (l-DOPA) to neurotoxic dopachrome catalyzed by enzyme horseradish
      peroxidase (EC 1.11.1.7) using the kinetic (KIE), and solvent (SIE), isotope
      effect methods. For kinetic studies two specifically deuterated isotopomers:
      [2',5',6'-2H3]-l-DOPA was synthesized by the acid catalyzed isotopic exchange
      between native l-DOPA and heavy water, and [5'-2H]-l-DOPA was synthesized in two
      step reaction. The first step involved acid catalyzed isotopic exchange between l
      tyrosine and deuterated water and resulting product [3',5'-2H2]-l-tyrosine was
      hydroxylated by enzyme tyrosinase (EC 1.14.18.1). The values of deuterium KIEs
      and SIE's in the enzymatic oxidation of l-DOPA and its isotopomers are determined
      using non-competitive spectrophotometric method. The measured values were: KIE on
      Vmax (1.1 and 2.2) and KIE on Vmax/KM (1.7 and 3.2) for [2',5',6'-2H3]-l-DOPA and
      [5'-2H]-l-DOPA, respectively, while the corresponding values of SIE were: SIE on
      Vmax (2.1, 2.4, and 2.1) and SIE on Vmax/KM (1.3. 1.6, and 1.1) for l-DOPA,
      [2',5',6'-2H3]-l-DOPA, and [5'-2H]-l-DOPA, respectively. The size of KIE and SIE,
      typical for secondary isotope effects indicate that both the solvent and presence
      of deuterium at the 2'-, 5', and 6'-positions of l-DOPA has the little impact on
      the enzymatic oxidation of this compound.

PMID- 26224963
TI  - Bioaccumulation of gamma emitting radionuclides in Polysiphonia fucoides.
AB  - The article presents the results of a study on the bioaccumulation abilities of
      Polysiphonia fucoides, a red algae specific to the southern Baltic Sea, towards
      (of) gamma emitting isotopes. A laboratory experiment was carried out to
      determine changes in the activities of some isotopes-54Mn, 57Co, 65Zn,
      110mAg,113Sn, 134Cs, 137Cs and 241Am-occurring in P. fucoides exposed to a
      seawater medium containing these isotopes over the course of 1 month. All
      analyzed isotopes showed the greatest increase of radioactive activity in plant
      tissue in the first 24 h of exposure. The temporary concentration factors of
      cesium isotopes were increasing linearly during the experiment from 114 to 274 in
      the case of 137Cs, and from 144 to 351 in the case of 134Cs. The level of the
      initial concentration factor of cesium isotopes in the plant proved to be
      independent of the initial concentration of the isotope in seawater and it took
      the lowest (125 dm3 kg-1) level among the studied isotopes. In the case of a
      mixture of gamma emitting isotopes, a linear relation between the individual
      isotope activity in P. fucoides and its initial concentration in seawater was
      established after the first day of exposure; the isotopes initial concentration
      factors ranged from 767 to 874 dm3 kg-1. Having reached the maximal concentration
      level, a statistically significant decline in radioactivity concentrations of the
      five isotopes in the plant tissue was observed. A half-life of biological removal
      of the isotopes from the plant tissue was established at: 3.8 days in the case of
      54Mn, 4 days-57Co, 4 days-60Co, 4.2 days-137Cs and 241Am-3.5 days.

PMID- 26224962
TI  - Plutonium, 90Sr and 241Am in human bones from southern and northeastern parts of
      Poland.
AB  - The paper presents the results of our study on 238Pu, 239Pu, 240Pu, 241Am and
      90Sr concentration in human bones carried out on a set of 88 individual samples
      of central Europe origin. Bone tissue samples were retrieved under surgery while
      introducing hip joint implants. The conducted surgeries tend to cover either
      southern or northeastern parts of Poland. While for the southern samples only
      global fallout was expected to be seen, a mixed global and Chernobyl fallout were
      to be reflected in the others. Alpha spectrometry was applied to obtain activity
      concentration for 238Pu, 239+240Pu, 241Am, while liquid scintillation
      spectrometry for 90Sr and mass spectrometry to receive 240Pu/239Pu mass ratio.
      Surprisingly enough, and to the contrary to our expectations we could not see any
      significant differences in either Pu activity or Pu mass ratio between the
      studied populations. In both populations Chernobyl fraction proved marginal. The
      results on 90Sr and 241Am confirm similarities between the two examined groups.

PMID- 26224964
TI  - Monitoring 60Co activity for the characterization of the sorption process of Co2+
      ions in municipal activated sludge.
AB  - In large volumes produced activated sludges from wastewater treatment plants
      (WWTPs) with low concentrations of heavy metals can be utilized as agricultural
      fertilizers and soil conditioners. Increased contents of toxic xenobiotics are
      limiting factors that affect the utilization of these heterogeneous wastes. The
      main aim of our paper was to show the utilization of dried activated sludge (DAS)
      from municipal WWTP as potential Co2+ ions sorbent i.e. for non-agricultural
      purposes. The radio indicator method by radionuclide 60Co and gamma-spectrometry
      for characterization DAS sorption properties was used. DAS soluble and solid
      fractions were characterized by biochemical, ETAAS and CEC analysis. The sorption
      of Co2+ ions by DAS was rapid process and equilibrium was reached within 2 h.
      Sorption capacity of DAS (Q) increased with the initial concentration of CoCl2 in
      the range from 100 to 4,000 MUmol l-1, reaching 20 and 160 MUmol g-1. Obtained Q
      values were depent on pH value from 2.0 to 8.0. The maximum sorption capacity
      (Qmax) of DAS at pH 6 calculated from mathematical model of Langmuir adsorption
      isotherm was 175 +/- 9 MUmol g-1. FT-IR analyses showed the crucial role of
      carboxyl functional groups of DAS surfaces on cobalt uptake. For confirmation ion
      exchange mechanism in sorption process of Co2+ ions by DAS scanning electron
      microscopy and EDX analysis were used.

PMID- 26224965
TI  - Interaction of 3H+ (as HTO) and 36Cl- (as Na36Cl) with crushed granite and
      corresponding fracture infill material investigated in column experiments.
AB  - The transport of 3H+ (as HTO) and 36Cl- (as Na36Cl) was investigated in the
      dynamic system, i.e., in the columns filled with crushed pure granite and
      fracture infill of various grain sizes. The aim of column experiments was to
      determine important transport parameter, such as the retardation, respectively
      distribution coefficients, Peclet numbers and hydrodynamic dispersion
      coefficients. Furthermore, the research was focused to quantification of the
      effect of grain size on migration of studied radionuclides. The experimental
      breakthrough curves were fitted by a model based on the erfc-function, assuming a
      linear reversible equilibrium sorption/desorption isotherm, and the above
      mentioned transport parameters were determined. The results showed that influence
      of grain size on sorption of 3H+ and 36Cl- was negligible. Retardation and
      distribution coefficients of both tracers converged to one and zero,
      respectively, in case of all fractions of crushed granite and infill material.
      Generally, the presumed ion exclusion of 36Cl in anionic form was proved under
      given conditions, only very weak one seems to exist in a case of infill material.
      In principal, both radionuclides behaved as non-sorbing, conservative tracers. On
      the other hand, the influence of grain size on Peclet numbers value and on
      dispersion coefficient was observed for both crystalline materials, namely in
      agreement with theoretical suppositions that the values of Peclet numbers
      decrease with increasing grain size and values of dispersion coefficient
      increase.

PMID- 26224966
TI  - Rapid method for plutonium-241 determination in soil samples.
AB  - A simple and rapid procedure for the determination of plutonium isotopes in the
      environment is presented. The procedure combines alpha spectrometry, solvent
      extraction and liquid scintillation measurements to ensure that both alpha- and
      beta-emitting isotopes are determined. Of five tested extractants, bis-(2
      ethylhexyl) phosphoric acid was found to be the best choice. The procedure was
      applied to soil samples contaminated with Chernobyl fallout.

PMID- 26224967
TI  - Adsorption of citrate ions on hydroxyapatite synthetized by various methods.
AB  - The specific adsorption of citric acid ions at hydroxyapatite interface was
      investigated by the means of radioisotope method (14C) as a function of citric
      acid ions concentration, NaCl concentration and pH. Application of the
      hydroxyapatite has become wide in the biomaterial field as the Ca10(OH)2(PO4)6
      possess biocompatibility with human hard tissue. Hydroxyapatite was synthesized
      using three different methods. The physical properties of the resulting powder
      were characterized by DTA/TG, XRD, AFM and SEM microscopy. Physicochemical
      qualities characterizing the electrical double layer of the hydroxyapatite/NaCl
      solution interface were determined. The zeta potential and the adsorption of
      citric acid molecule were studied as a function of pH. The point of zero charge
      and the isoelectric point of samples were determined. Electrical double layer
      parameters of hydroxyapatite/NaCl interface are influenced by a synthesis method.
      The points pHpzc and pHIEP for sample 1 are pHpzc 7.5 and pHIEP 3; for sample 2
      pHpzc 7.05 and pHIEP 3, for smaple 3 pHpzc 6.7 and pHIEP 3. Temperature has weak
      influence both on pure substance and with citric acid adsorbed, as
      derivatographic analysis has shown, and characterization of hydroxyapatite
      structure may be carried out by this thermal analysis. Two phenomena are
      responsible for citric acid adsorption: phosphate group's replacement at
      hydroxyapatite surface by citric ions parallel to intraspherical complexes
      formation.

PMID- 26224968
TI  - Thin layer spectroelectrochemical (RVC-OTTLE) studies of pertechnetate reduction
      in acidic media.
AB  - The electroreduction of the pertechnetate ions has been examined in sulfuric acid
      solutions (0.5-4 M) using optically transparent thin layer spectroelectrochemical
      (RVC-OTTLE) cell. Soluble Tc(III), TcO2+ and [Tc(MU-O)2Tc]3+/4+ species with
      absorption bands at 420-450, 400, and 502 nm, respectively, were found to be
      formed during the reduction of TcO4- ions. The strongly acidic medium was found
      to stabilize technetium ionic forms with lower oxidation states.
      Spectroelectrochemical measurements performed in 4 M H2SO4 show different
      stability of dimeric structure of Tc(III, IV) and simple TcO2+ ions. The
      monooxotechnetium(IV) ions can be electrooxidized at potentials lower than 0.6 V
      versus Ag,AgCl(sat.) while dimeric structures of Tc, [Tc(MU-O)2Tc]3+/4+, are
      electrooxidized to pertechnetate ions at potentials higher than 0.8 V versus
      Ag,AgCl(sat.).

PMID- 26224969
TI  - Optimization of the heavy metal (Bi-W-Gd-Sb) concentrations in the elastomeric
      shields for computer tomography (CT).
AB  - Eight elastomeric composites (NRU, GR1-GR4, NRBG08-NRBG24) containing mixtures of
      different proportions of heavy metal additives (Bi, W, Gd and Sb) have been
      synthesized and examined as protective shields. The NRU sample was a pure rubber
      matrix and served as a reference sample for heavy metal modified composites.
      Experimental procedure used for evaluation of the composite shields and their
      attenuation properties was based on the utilization of HPGe spectrometry and
      analysis of X-ray fluorescence radiation intensity of the heavy metal additives
      in the following energy ranges for: Sb (20-35 keV), Gd (35-55 keV), W (55-70 keV)
      and Bi (70-90 keV). The main contributor to the induced X-ray fluorescence
      radiation within the shield is Bi additive and the intensity of the X-ray
      radiation generated within the energy range of 70-90 keV strongly depends on its
      concentration. It was found that decreasing concentration of the Bi fraction from
      0.35 (GR samples) to 0.15 (NRBG samples) results in significant lowering Bi X-ray
      fluorescence radiation within the 70-90 keV energy range. Secondary effect of
      decreasing Bi concentration was efficient diminishing excitation processes for
      lower Z heavy metal additives (W, Gd and Sb, GR vs. NRBG samples). As the final
      quality parameter of the shielding properties for the examined elastomers, dose
      reduction factor (DRF) coefficients were calculated for each shield. It was
      found, that the best shielding properties are observed for composites with lower
      Bi concentration (0.15 vs. 0.35 Bi mass fraction) with only slight further
      improvement of their parameters (DRF) with increasing of Gd concentration (Gd
      mass fraction 0.08, 0.16 and 0.24). The most efficient dose reduction composite
      was found to be NRBG24 elastomer with DRF value 0.47 (53 % dose reduction) for
      ca. 2 mm and 0.44 g/cm2 layer thickness.

PMID- 26224970
TI  - Intercomparison of diffusion coefficient derived from the through-diffusion
      experiment using different numerical methods.
AB  - Diffusion is a dominant mechanism regulating the transport of released nuclides.
      The through-diffusion method is typically applied to determine the diffusion
      coefficients (D). Depending on the design of the experiment, the concentrations
      in the source term [i.e., inlet reservoir (IR)] or the end term [i.e., outlet
      reservoir (OR)] can be fixed or vary. The combinations involve four distinct
      models (i.e., the CC-CC model, CC-VC model, VC-CC model, and the VC-VC model).
      Studies discussing the VC-CC model are scant. An analytical method considering
      the decay effect is required to accurately interpret the radioactive nuclide
      diffusion experiment results. Therefore, we developed a CC-CC model and a CC-VC
      model with a decay effect and the simplified formulas of these two models to
      determine the diffusion coefficient (i.e., the CC-CC method and CC-VC method). We
      also proposed two simplified methods using the VC-VC model to determine the
      diffusion coefficient straightforwardly based upon the concentration variation in
      IR and OR. More importantly, the best advantage of proposed method over others is
      that one can derive three diffusion coefficients based on one run of experiment.
      In addition, applying our CC-VC method to those data reported from Radiochemica
      Acta 96:111-117, 2008; and J Contam Hydrol 35:55-65, 1998, derived comparable
      diffusion coefficient lying in the identical order of magnitude. Furthermore, we
      proposed a formula to determine the conceptual critical time (Tc), which is
      particularly beneficial for the selection of using CC-VC or VC-VC method. Based
      on our proposed method, it becomes possible to calculate diffusion coefficient
      from a through-diffusion experiment in a shorter period of time.

PMID- 26224971
TI  - Activity disequilibrium between 234U and 238U isotopes in natural environment.
AB  - The aim of this work was to calculate the values of the 234U/238U activity ratio
      in natural environment (water, sediments, Baltic organisms and marine birds from
      various regions of the southern Baltic Sea; river waters (the Vistula and the
      Oder River); plants and soils collected near phosphogypsum waste heap in Wislinka
      (Northern Poland) and deer-like animals from Northern Poland. On the basis of the
      studies it was found that the most important processes of uranium geochemical
      migration in the southern Baltic Sea ecosystem are the sedimentation of suspended
      material and the vertical diffusion from the sediments into the bottom water.
      Considerable values of the 234U/238U are characterized for the Vistula and Oder
      Rivers and its tributaries. The values of the 234U/238U activity ratio in
      different tissues and organs of the Baltic organisms, sea birds and wild deer are
      varied. Such a large variation value of obtained activity ratios indicates
      different behavior of uranium isotopes in the tissues and organisms of sea birds
      and wild animals. This value shows that uranium isotopes can be disposed at a
      slower or faster rate. The values of the 234U/238U activity ratio in the analyzed
      plants, soils and mosses collected in the vicinity of phosphogypsum dumps in
      Wislinka are close to one and indicate the phosphogypsum origin of the analyzed
      nuclides. Uranium isotopes 234U and 238U are not present in radioactive
      equilibrium in the aquatic environment, which indicates that their activities are
      not equal. The inverse relationship is observed in the terrestrial environment,
      where the value of the of the 234U/238U activity ratio really oscillates around
      unity.

PMID- 26224972
TI  - Cosmogenic 22Na, 7Be and terrestrial 137Cs, 40K radionuclides in ground level air
      samples collected weekly in Krakow (Poland) over years 2003-2006.
AB  - A low background gamma spectrometer with an Etruscan, 2500 years old lead shield
      and a muon veto detector were applied to study 22Na and 7Be activity
      concentration in ground level air aerosol samples collected weekly over the years
      2003-2006 in Krakow. Each sample was formed with ca 100 000 m3 of passed air,
      collected with two parallel ASS-500 high volume air samplers. The results for 40K
      and 137Cs are also presented for reference and comparison. Presented frequency
      distributions for activity concentration and correlation between the obtained
      results are discussed. The activity concentration results confirmed seasonal
      variation of activity to be different for all the investigated radionuclides.
      Moreover, the seasonal variation in nucleus activity ratio was also noticed for
      22Na and 7Be. Cosmogenic radionuclides being mainly of stratospheric origin, are
      subsequently attached to fine aerosols, via which they are transported to the
      ground level air. The mean aerosol transport time within the troposphere was
      estimated as equal to 7.5 days on average, reaching even 50 days in warm seasons.
      Limitations of the applied model were identified.

PMID- 26224973
TI  - Variation of counting efficiency in determination of 131I activity in the thyroid
      gland as a result of its position relative to the detector.
AB  - The appropriate determination of the 131I which was absorbed into the human body,
      especially by thyroid, depends not only on individual features of each
      measurement subjects but also on reproducibility of their position or the
      thyroid's position in the human neck. Possible uncertainties caused by changes of
      the thyroid position relative to detector were studied in a series of
      measurements. The research has shown that the dispersion of the results can reach
      up even to the level of 50 %.

PMID- 26224974
TI  - Cs-137 in the natural environment of the Gorce Mountains (Poland).
AB  - Concentration of activity of Cs-137 and its spatial distribution in soils and
      lichen Hypogymnia physodes were determined in the Gorce Mts. (several hundred
      km2) in S Poland. The authors distinguished two areas of the Gorce Mts. on the
      basis of markedly different Cs-137 depositions, whose respective average values
      are 4.4 and 9.9 kBq/m2 as at 1st July 2005. The average Cs-137 activity
      concentration in the lichen H. physodes from the Gorce is 47 Bq/kg d.m. A
      significant local variability of quantities measured amounts to a few dozen
      percent was found.

PMID- 26224975
TI  - 222Rn and 226Ra activity concentrations in groundwaters of southern Poland: new
      data and selected genetic relations.
AB  - Since 2008, the authors have been conducting research into 222Rn and 226Ra
      activity concentrations in shallow circulation groundwaters in southern Poland.
      Measurements have been performed with a liquid-scintillation method and ultra low
      level liquid-scintillation spectrometers alpha/beta Quantulus 1220. The research
      carried out so far has demonstrated that in the Sudetes groundwaters with high
      activity concentrations of 222Rn and 226Ra are common. In other studied areas in
      southern Poland no shallow circulation groundwaters with high radon or radium
      concentrations have been found yet. The conducted research has demonstrated that
      the activity concentration of 222Rn dissolved in shallow circulation groundwaters
      in the Sudetes depends chiefly on the amount of radon, which after being released
      as gas from reservoir rocks is dissolved in waters flowing through these rocks.
      At the same time, the concentration of 222Rn dissolved in some shallow
      circulation groundwaters in the Carpathians is influenced significantly by the
      amount of radon produced from the decay of its parent ion 226Ra2+ dissolved in
      these waters.

PMID- 26224976
TI  - Adsorption of 137Cs on titanate nanostructures.
AB  - Various types of sodium and potassium titanate nanostructures (nanotubes,
      nanofibers, nanoribbons, nanwires) were synthesized and characterized by X-ray
      diffraction, SEM and TEM, as well BET and BJH methods. Adsorption of radiotracer
      137Cs+ ions from aqueous solutions on synthesized titanate nanostructures was
      investigated in batch technique as a function of contact time, concentration of
      sodium ions and pH of the solutions. It was found that among the studied
      nanostructures nanotubes shows the highest selectivity for 137Cs, which is
      related to a zeolitic character of Cs+ adsorption. The efficient adsorption of
      137Cs was obtained in Na+ solutions with concentration below 10-2 M, at pH 7-9
      and in contact time above 2 h. Moreover, nanotubes have the higher specific
      surface area than other nanostructures, which results in better availability of
      ion exchange groups and high ion exchange capacity. These properties of nanotubes
      indicate that they may be used for adsorption of 137Cs from various types of
      nuclear wastes.

PMID- 26224977
TI  - Kinetic study of uranium residue dissolution in ammonium carbonate media.
AB  - The purpose of this study was to determine the kinetics of the dissolution of a
      uranium residue in ammonium carbonate media. The residue is generated in the
      production of medical isotopes. The effects of parameters, such as varying
      peroxide and carbonate concentrations, dissolution time as well as temperature on
      the extraction rate have been separately studied. Results indicate complete
      dissolution of the residue at 60  degrees C, after 30 min, in ammonium carbonate
      solution enriched with hydrogen peroxide. The yield and rate of uranium
      extraction were found to increase as a function of both temperature, in the range
      of 25-60  degrees C, and hydrogen peroxide concentration. The extraction process
      was governed by chemical reaction as the activation energy was found to be 45.5
      kJ/mol. The order of reaction with respect to uranium concentration was found to
      be approximately first order.

PMID- 26224978
TI  - Adsorption of 137Cs on titanium ferrocyanide and transformation of the sorbent to
      lithium titanate: a new method for long term immobilization of 137Cs.
AB  - Dynamic adsorption of radiocesium on titanium ferrocyanide grains from reactor
      coolant simulating solution containing salts at moderate concentrations has been
      investigated. Effective decontamination of the neutral solutions has been
      achieved, in the amounts of a more than 20 thousand bed volumes. After adsorption
      the titanium ferrocyanide was transferred to titanates and calcined at 900 
      degrees C. The leaching test of the obtained lithium titanates indicates that the
      loaded adsorbent can serve as an effective primary barrier in nuclear waste
      repositories.

PMID- 26224979
TI  - Mineralogy and uranium leaching of ores from Triassic Peribaltic sandstones.
AB  - The recovery of uranium and other valuable metals from Polish Peribaltic
      sandstones were examined. The solid-liquid extraction is the first stage of the
      technology of uranium production and it is crucial for the next stages of
      processing. In the laboratory experiments uranium was leached with efficiencies
      71-100 % by acidic lixiviants. Satisfactory results were obtained for the
      alkaline leaching process. Almost 100 % of uranium was leached with alkaline
      carbonate solution. In post leaching solutions only uranium and small amounts of
      vanadium were present.

PMID- 26224980
TI  - Quick algorithms for real-time discrimination of neutrons and gamma rays.
AB  - Several new methods for the digital discrimination of neutrons and gamma-rays in
      a mixed radiation field are presented. The methods introduced discriminate
      neutrons and gamma rays successfully in the digital domain. They are
      mathematically simple and exploit samples during the life time of the pulse,
      hence appropriate for field measurements. All these methods are applied to a set
      of mixed neutron and photon signals from a stilbene scintillator and their
      discrimination qualities are compared.

PMID- 26224981
TI  - Use of radiometric (234/238U and 228/226Ra) and mass spectrometry (87/86Sr)
      methods for studies of the stability of groundwater reservoirs in Central Poland.
AB  - The uranium (234U/238U) and radium (228Ra/226Ra) activity ratios and 87Sr/86Sr
      isotopic ratio in thermal groundwater, subsurface water (groundwater) and river
      water from Poddebice and Uniejow were determined. The uranium and radium activity
      ratios and strontium isotopic ratio varied from 0.629 to 1.471, from 0.396 to
      4.961 and from 0.708438 to 0.710344, respectively. The results for the thermal
      groundwater samples showed that the radiometric method together with mass
      spectrometry stable strontium isotope ratio measurements can be used for
      underground water transport studies. On the basis of the uranium and radium
      activity and the strontium isotopic ratio differences in subsurface water
      (groundwater) and in river water, any possible water influx between these
      adjacent reservoirs can be observed. The obtained results exclude any water
      transport from surface and subsurface water to thermal ground water reservoirs in
      this region of Poland.

PMID- 26224982
TI  - Extraction of natural radionuclides from aqueous solutions by novel maltolate
      based task-specific ionic liquids.
AB  - Two novel maltol-based ionic liquids, namely [A336][Mal] and [C101][Mal], were
      synthesized as potential extracting agents for radionuclides from water. These
      two room temperature task-specific ionic liquids could be easily prepared by
      anion metathesis starting from commercially available materials. The isolated
      compounds were characterized by standard analytical methods. Their application as
      extraction agent for Unat., 234Th, 210Pb, 210Bi, 210Po and 226Ra was elucidated
      by liquid-liquid extraction and scintillation counting. Uranium was totally
      extracted by both ionic liquids over a broad pH range (2-8), while the other
      radionuclides were removed with differing efficacies depending on the respective
      pH value.

PMID- 26224983
TI  - Radionuclide monitoring in foodstuff: overview of the current implementation in
      the EU countries.
AB  - The Member States (MS) of the European Union (EU) are obliged to monitor the
      radioactivity in the environment since the signature of the Euratom Treaty
      (Treaty establishing the European Atomic Energy Community). Numerous secondary
      legislations derived from the Treaty can be found stating restrictions and
      maximum permitted levels of radionuclides in foodstuff. But to that purpose, no
      common integrated measurement methods are used with well-defined measurands. The
      present work consists of two parts. First, the current European regulations in
      force were collected, and then the food monitoring results, provided by the MS,
      were analysed.

PMID- 26224984
TI  - Determination of uranium reference levels in the urine of Warsaw residents
      (Poland).
AB  - This paper presents the results of determination of activity concentration of
      238U and 234U in urine samples of people living in Warsaw (capital of Poland) to
      evaluate background level of these radionuclides excretion rate (mBq day-1). The
      samples were taken from women and men in age between 3 and 97 years. The results
      obtained for 238U daily excretion rate were in range 0.44-30.54 mBq day-1 and for
      234U in range 0.33-28.61 mBq day-1. 70 % results were below 6 mBq day-1 upper
      limit recommended by ICRP for non-exposed people (ICRP, ICRP publications No. 23,
      report of the task group on reference man, 1975). The results are discussed and
      some conclusions based upon average values were drawn.

PMID- 26224986
TI  - Development of a versatile sample preparation method and its application for rare
      earth pattern and Nd isotope ratio analysis in nuclear forensics.
AB  - An improved sample preparation procedure for trace-levels of lanthanides in
      uranium-bearing samples was developed. The method involves a simple co
      precipitation using Fe(III) carrier in ammonium carbonate medium to remove the
      uranium matrix. The procedure is an effective initial pre-concentration step for
      the subsequent extraction chromatographic separations. The applicability of the
      method was demonstrated by the measurement of REE pattern and 143Nd/144Nd isotope
      ratio in uranium ore concentrate samples.

PMID- 26224985
TI  - Monitoring of radioactive contamination in Polish surface waters in 2012-2013.
AB  - The 90Sr and 137Cs contamination in Polish surface waters has been monitoring
      since 1994. Surface water samples from six lakes and the Vistula and Oder Rivers
      were collected in spring and autumn 2012 and 2013. The mean 90Sr and 137Cs
      concentrations were 3.92 +/- 0.40 and 4.49 +/- 2.00 mBq L-1, respectively.
      Correlations were identified between the radionuclide concentrations and
      meteorological conditions and the original fallout distribution from the
      Chernobyl disaster. The annual average radionuclide concentrations were not
      significantly different from the concentrations found between 1994 and 2011. The
      137Cs and 90Sr concentrations have been decreasing only slowly.

PMID- 26224988
TI  - Challenges in the quality assurance of elemental and isotopic analyses in the
      nuclear domain benefitting from high resolution ICP-OES and sector field ICP-MS.
AB  - Accurate analytical data reinforces fundamentally the meaningfulness of nuclear
      fuel performance assessments and nuclear waste characterization. Regularly
      lacking matrix-matched certified reference materials, quality assurance of
      elemental and isotopic analysis of nuclear materials remains a challenging
      endeavour. In this context, this review highlights various dedicated experimental
      approaches envisaged at the European Commission-Joint Research Centre-Institute
      for Transuranium Elements to overcome this limitation, mainly focussing on the
      use of high resolution-inductively coupled plasma-optical emission spectrometry
      (HR-ICP-OES) and sector field-inductively coupled plasma-mass spectrometry (SF
      ICP-MS). However, also alpha- and gamma-spectrometry are included here to help
      characterise extensively the investigated actinide solutions for their actual
      concentration, potential impurities and isotopic purity.

PMID- 26224987
TI  - 99mTc-3P-RGD2 molecular imaging targeting integrin alphavbeta3 in head and neck
      squamous cancer xenograft.
AB  - 99mTc-3P-RGD2 and SPECT/CT were valuable tools for selecting patient likely
      benefit from integrin alphavbeta3 blocking therapy. To evaluate the feasibility
      of 99mTc-3P-RGD2 imaging to detect head and neck squamous cell carcinoma, 99mTc
      3P-RGD2 was prepared and the relationship between its accumulation and integrin
      alphavbeta3 expression in nude mice bearing HEP-2 or CNE-1 carcinoma xenograft
      were analyzed. This study demonstrated that 99mTc-3P-RGD2, with high affinity to
      integrin alphavbeta3, will provide basis for alphavbeta3 involved individual
      therapy.

PMID- 26224989
TI  - Development of synthetic nuclear melt glass for forensic analysis.
AB  - A method for producing synthetic debris similar to the melt glass produced by
      nuclear surface testing is demonstrated. Melt glass from the first nuclear weapon
      test (commonly referred to as trinitite) is used as the benchmark for this study.
      These surrogates can be used to simulate a variety of scenarios and will serve as
      a tool for developing and validating forensic analysis methods.

PMID- 26224990
TI  - Future U.S. supply of Mo-99 production through fission based LEU/LEU technology.
AB  - Coqui RadioPharmaceuticals Corp. (Coqui) has the goal of establishing a medical
      isotope production facility for securing a continuous domestic supply of the
      radioisotope molybdenum-99 for U.S. citizens. Coqui will use an LEU/LEU proven
      and implemented open pool, light-water, 10 MW, reactor design. The facility is
      being designed with twin reactors for reliability an on-site hot lab chemical
      processing and a waste conditioning area and a possible generator producing radio
      chemistry lab. Coqui identified a 25 acre site adjacent to an existing industrial
      park in northern central Florida. This land was gifted and transferred to Coqui
      by the University of Florida Foundation. We are in the process of developing
      licensing documents related to the facility. The construction permit application
      for submission to the U.S. Nuclear Regulatory Commission is currently being
      prepared. Submission is scheduled for mid to late 2015. Community reaction to the
      proposed development has been positive. We expect to create 220 permanent jobs
      and we have an anticipated to be operational by 2020.

PMID- 26224991
TI  - Behavior of technetium in nuclear waste vitrification processes.
AB  - Nearly 100 tests were performed with prototypical melters and off-gas system
      components to investigate the extents to which technetium is incorporated into
      the glass melt, partitioned to the off-gas stream, and captured by the off-gas
      treatment system components during waste vitrification. The tests employed
      several simulants, spiked with 99mTc and Re (a potential surrogate), of the low
      activity waste separated from nuclear wastes in storage in the Hanford tanks,
      which is planned for immobilization in borosilicate glass. Single-pass technetium
      retention averaged about 35 % and increased significantly with recycle of the off
      gas treatment fluids. The fraction escaping the recycle loop was very small.

PMID- 26224992
TI  - A Case Study of Early Development in Williams Syndrome: Implications for Early
      Intervention.
AB  - The aim of this article is to provide an in-depth description of the behavioral
      phenotype of Williams syndrome in a preschool-aged child. Williams syndrome is a
      neurodevelopmental, multisystem genetic disorder associated with mental
      retardation that predisposes individuals to a characteristic pattern of strengths
      and weaknesses in neuropsychological functioning. While much is known about
      functioning in adults, very few descriptions of early development are available
      in the literature. Implications for designing early intervention programs for
      children with this debilitating disorder are discussed.

PMID- 26224993
TI  - On the rotational equations of motion in rigid body dynamics when using Euler
      parameters.
AB  - Many models of three-dimensional rigid body dynamics employ Euler parameters as
      rotational coordinates. Since the four Euler parameters are not independent, one
      has to consider the quaternion constraint in the equations of motion. This is
      usually done by the Lagrange multiplier technique. In the present paper, various
      forms of the rotational equations of motion will be derived, and it will be shown
      that they can be transformed into each other. Special attention is hereby given
      to the value of the Lagrange multiplier and the complexity of terms representing
      the inertia forces. Particular attention is also paid to the rotational
      generalized external force vector, which is not unique when using Euler
      parameters as rotational coordinates.

PMID- 26224994
TI  - ESR and X-ray Structure Investigations on the Binding and Mechanism of Inhibition
      of the Native State of Myeloperoxidase with Low Molecular Weight Fragments.
AB  - As an early visitor to the injured loci, neutrophil-derived human Myeloperoxidase
      (hMPO) offers an attractive protein target to modulate the inflammation of the
      host tissue through suitable inhibitors. We describe a novel methodology of using
      low temperature ESR spectroscopy (6 K) and FASTTM technology to screen a diverse
      series of small molecules that inhibit the peroxidase function through reversible
      binding to the native state of MPO. Our initial efforts to profile molecules on
      the inhibition of MPO-initiated nitration of the Apo-A1 peptide (AEYHAKATEHL)
      assay showed several potent (with sub-micro molar IC50s) but spurious inhibitors
      that either do not bind to the heme pocket in the enzyme or retain high (>50 %)
      anti oxidant potential. Such molecules when taken forward for X-ray did not yield
      inhibitor-bound co-crystals. We then used ESR to confirm direct binding to the
      native state enzyme, by measuring the binding-induced shift in the electronic
      parameter g to rank order the molecules. Molecules with a higher rank order-those
      with g-shift Rrelative >=15-yielded well-formed protein-bound crystals (n = 33
      structures). The co-crystal structure with the LSN217331 inhibitor reveals that
      the chlorophenyl group projects away from the heme along the edges of the Phe366
      and Phe407 side chain phenyl rings thereby sterically restricting the access to
      the heme by the substrates like H2O2. Both ESR and antioxidant screens were used
      to derive the mechanism of action (reversibility, competitive substrate
      inhibition, and percent antioxidant potential). In conclusion, our results point
      to a viable path forward to target the native state of MPO to tame local
      inflammation.

PMID- 26224995
TI  - Missing species among Mediterranean non-Siphonophoran Hydrozoa.
AB  - Hydrozoa of the Mediterranean Sea are well known and a recent monograph covers
      457 species. Mediterranean non-Siphonophoran Hydrozoa comprises 398 species, an
      increasing number due to continuous updates, representing about 10 % of the 3,702
      currently valid species reported in a recent world assessment of hydrozoan
      diversity. Many new records are non indigenous species, previously described
      species that occurred elsewhere and whose arrival was presumably caused by human
      activities. However, many species reported in the past are not recorded in recent
      times. Realistic assessments of species pools require addition of new species,
      but also subtraction of species not found since a certain period. With the
      confidence of extinction index, cases of putative extinction can be raised. Out
      of the 398 known species, only 162 (41 %) have been reported in the last decade,
      while 53 (13 %) are not recorded in the literature since at least 41 years.
      According to the confidence of extinction index, 60 % of the 53 missing species
      are extinct, and 11 % are putatively extinct from the basin. From a
      biogeographical point of view, the missing species are: 34 % endemic, 19 %
      boreal, 15 % Mediterranean-Atlantic, 11 % Indo-Pacific, 11 % circumtropical, 4 %
      cosmopolitan, 2 % tropical-Atlantic, 4 % non-classifiable. Fluctuations in
      species composition into a certain area cause heavy variability in the expression
      of both structural and functional biodiversity. As consequence, the regional
      biodiversity should be analyzed through its temporal evolution, to detect changes
      and their possible causes. This approach has profound consequences on
      biodiversity assessments and also on the compilation of red lists.

PMID- 26224996
TI  - The maxillofacial surgeon's march towards a smarter future-smartphones.
AB  - The latest mobile phone in addition to being a communication device now is also
      able to do most functions of a computer. These mobile devices are now called
      smartphones. These smartphones can use various applications (called apps) which
      have revolutionized the use of these devices. We discuss the uses of smartphones
      in maxillofacial surgery and how they have made the work of the maxfac surgeon
      easier. 

PMID- 26224997
TI  - Autogenous Reconstructive Modalities of TMJ Ankylosis-A Retrospective Analysis of
      45 Cases.
AB  - The study reports the authors' experience in managing temporomandibular joint
      (TMJ) ankylosis in Chennai, India (1995-2006) and compares the surgical
      modalities used. Forty-five patients (67 joints) were reviewed in this
      retrospective study. Pre- and post-operative assessment included history,
      radiological, physical examination, and range of mouth opening. Age, gender,
      aetiology, joint(s) affected, surgical modality, complications and follow-up
      periods were evaluated. Various types (fibrous, fibroosseous and bony) of TMJ
      ankylosis were diagnosed. Trauma was the commonest aetiology. The patients' age
      range was 2-50 years, 51.1 % were males and the follow-up period ranged from 14
      to 96 months. Average mouth opening was significantly increased to 32 mm 12
      months post-operatively. Mouth opening was compared following different
      interpositional materials like temporalis interpositioning (33 mm), costochondral
      graft (30.6 mm) and autograft (30 mm). Minor and major complications were
      encountered in 37.4 % of cases, including 6.7 % recurrence rate. Early release of
      TMJ ankylosis; reconstruction of the ramus height with distraction osteogenesis
      or bone grafting combined with interpositional arthroplasty, followed by vigorous
      physiotherapy is a successful strategy for the management of TMJ ankylosis. 

PMID- 26224998
TI  - Nasotracheal Intubation: An Overview.
AB  - INTRODUCTION: Nasotracheal intubation is the commonest method used to induce
      anaesthesia in oral surgery patients. It has a distinct advantage of providing
      good accessibility for oral surgical procedures. ANATOMY AND PROCEDURE: One must
      know the anatomy involved, the pathway and procedure of intubation, the pre
      anaesthetic medication and complications which may be seen at the time of
      intubation. The surgeon must have the knowhow of the tube and the procedure which
      are explained in detail in the article. COMPLICATIONS: Several complications can
      arise while performing the procedure which may be operator induced or arising due
      to anatomical variations. CONCLUSION: It is prudent for the oral surgeon to know
      the basics of nasotracheal intubation in order to form a useful team member for
      management of complications arising from anaesthesia. Recent years have seen
      improvement in the armamentarium. These help negate the blindness of the
      procedure.

PMID- 26224999
TI  - Trigeminocardiac Reflex: A Reappraisal with Relevance to Maxillofacial Surgery.
AB  - PURPOSE: The purpose of this paper was to undertake a review of literature on
      trigeminocardiac reflex in oral and maxillofacial online data-base and discuss
      the pathophysiology, risk factor assessment, presentation of the reflex,
      prevention, management with emphasis on the role of the attending anaesthetist
      and the maxillofacial surgeon. MATERIALS AND METHODS: The available literature
      relevant to oral and maxillofacial surgery in online data-base of the United
      States National Library of Medicine: Pubmed (http://www.ncbi.nlm.nih.gov/pubmed/)
      was searched. The inclusion criterion was to review published clinical papers,
      abstracts and evidence based reviews on trigeminocardiac reflex relevant to oral
      and maxillofacial surgery. RESULTS: Sixty-five articles were found with the
      search term "trigeminocardiac reflex" in the literature searched. Eighteen
      articles met the inclusion criteria for this study. The relevant data was
      extracted, tabulated and reviewed to draw evidence based conclusions for the
      management of trigeminocardiac reflex. CONCLUSIONS: Conclusions were drawn and
      discussed based on the reviewed maxillofacial literature with emphasis on the
      anaesthetist's and the surgeon's role in the management of this detrimental event
      in maxillofacial surgical practice.

PMID- 26225000
TI  - A Comprehensive Proforma for Evaluation of Mandibular Third Molar Impactions.
AB  - We have developed a simple, but comprehensive proforma for evaluating mandibular
      third molar impactions and formulating a proper treatment plan. This proforma is
      aimed at residents in Oral and Maxillofacial Surgery, to help them during their
      initial phase, in evaluating and treating impacted mandibular third molars. This
      comprehensive proforma will help them to analyse third molar impactions, assess
      and anticipate the difficulty, judge intraoperative problems they might
      encounter, and evaluate the patient at post operative follow-up. 

PMID- 26225001
TI  - Bisphosphonate Related Osteonecrosis of the Jaw: An Update.
AB  - OBJECTIVES: The aim of this paper is to summarize different diagnostic criteria
      as well as probable aetiopathogenesis of bisphosphonates related osteonecrosis of
      the jaw. MATERIALS AND METHODS: The electronic search of peer-reviewed journals
      were performed in MEDLINE (PubMed) database in order to find the relevant
      articles on bisphosphonates related osteonecrosis of the jaw (BP-related ONJ).
      The search was restricted to English language articles, published from January
      2002 to May 2013. On the basis of these articles, probable aetiopathogenesis and
      different diagnostic criteria of BP-related ONJ were summarized. RESULTS: BP
      related ONJ is related to the development of avascular necrosis or dead jaw
      bones. In recent literature many given hypotheses show the aetiopathogenesis and
      diagnosis of BP-related ONJ which are interlinked and have multifactorial nature.
      Their diagnosis revolves around four main diagnostic criteria that differentiate
      it from other conditions which can delay bone healing. CONCLUSIONS: Factors like
      potency of bisphosphonates, biology of jaw bone, antiangiogenic property of
      bisphosphonates and soft tissue toxicity in combination with present infection,
      other drugs, pre-existing pathologies, compromised immune response and
      dentoalveolar trauma may lead to development of BP-related ONJ.

PMID- 26225002
TI  - New Management Strategies of Oral Tongue Cancer in Bangladesh.
AB  - INTRODUCTION: Malignancies of the tongue represent one of the greatest management
      challenges for the maxillofacial surgeons as well as oncologists, because of the
      adverse effects of treatment on oral and pharyngeal function, the eventual
      quality of life, and the poor prognosis of advanced disease. Therefore, it is
      important to use judgment and experience in determining the best method of
      treatment. MATERIAL AND METHODS: We reviewed forty cases of oral tongue cancer
      patients admitted in the Dental and Facio-Maxillary Surgical Oncology department
      in National Institute of Cancer Research and Hospital, and department of Oral and
      Maxillofacial Surgery, Dhaka Dental College and Hospital, Dhaka, Bangladesh,
      during the past four years and followed till the lesion healed or recurred and
      followed later on upto two years. All cases were thoroughly examined,
      investigated with routine blood examinations and radiography of the involved
      region. Preoperative biopsy of the lesion and staging was done in each and every
      case. Postoperative biopsy was taken where there was a doubt about the
      possibility of recurrence. RESULTS: Squamous cell carcinoma (well differentiated)
      is by far the most common malignancy of the oral tongue. Generally a correlation
      is recognized between tumor size, nodal presence, metastasis, and eventual
      prognosis. When surgeons detect oral tongue cancer at an early stage, they can
      often treat it with surgery or can, often treat it with surgery or radiation. In
      later stages the cancer may require a combination of surgery, radiation and
      chemotherapy. CONCLUSION: Standard and uniform protocol has not been explored
      till now for the practice in our country. So current management strategies of
      oral tongue cancer cannot be underestimated.

PMID- 26225003
TI  - Maxillary Sinus Augmentation with Autologous and Heterologous Bone Graft: A
      Clinical and Radiographic Report of Immediate and Delayed Implant Placement.
AB  - PURPOSE: The aim of this study was to evaluate cumulative survival rate of
      implants placed on augmented maxillary sinus using a mixture of autologous bone
      harvested from the maxillary tuberosity and bovine-derived HA and to assess the
      height of the grafted material through radiographic evaluation. METHODS: Thirty
      five patients were treated with maxillary sinus augmentation and 93 implant
      fixtures were installed. The height of the augmented sinus and the gain of bone
      volume were measured by Cone Beam CT Scan and intraoral radiographs immediately
      after augmentation and up to 48 months subsequently. Changes in the height of the
      sinus graft material were calculated radiographically. RESULTS: The cumulative
      survival rate was 98.92 % in all 93 implants. Additionally, normal healing
      process without any complication was observed in all patients. The original sinus
      height was a mean of 4.52 mm (range 2.0-6.4 mm) and the augmented sinus height
      was a mean of 14.1 mm (range 12.0-16.5 mm) after the surgery. The bone volume
      gain was a mean 9.613 mm (range 7-13 mm). CONCLUSIONS: Within the limitations of
      this study, it would appear from the clinical and radiographic results that the
      sinus lift procedure with autologous bone graft harvested from the maxillary
      tuberosity combined with deproteinized bovine bone allows for a predictable
      outcome regarding the amount of bone formation in sinus floor augmentation and
      the immediate placement of implants, when possible, is recommended.

PMID- 26225004
TI  - Lamotrigine Versus Pregabalin in the Management of Refractory Trigeminal
      Neuralgia: A Randomized Open Label Crossover Trial.
AB  - BACKGROUND: Carbamazepine (CBZ) formed the gold standard drug in trigeminal
      neuralgia (TN) treatment but faces high therapeutic failure. This defined the
      need to explore a second line of drug therapy. The study aimed at comparing two
      alternate drugs i.e. Lamotrigine (LTG) and Pregabalin (PGB), in the management of
      TN refractory to therapeutic doses of CBZ. METHODS: Twenty-two patients with
      diagnosis of refractory TN were enrolled and randomly allotted into 2 groups of
      11 each. Each group was subjected to a crossover analysis using LTG and PGB
      together with CBZ, for a period of 6 weeks. Patients maintained a pain diary, the
      scores of which, along with global evaluation scores, determined the primary
      outcome. Reevaluation of symptoms after 6 months was done to assess long term
      efficacy with study drugs. RESULTS: Both LTG and PGB were effective over CBZ
      alone (p < 0.05); however, statistically insignificant difference (p > 0.05) was
      observed between the two groups using Mann-Whitney tests. Unlike LTG, side
      effects like nausea, insomnia and concentration loss were minimal with PGB thus
      exhibiting greater patient compliance. Secondary analysis showed complete relief
      in 4 patients on PGB (mean dose 240.68 mg/day) while 6 had partial relief. Three
      patients on LTG (mean dose 310.90 mg/day) reported relapse of acute symptoms and
      required peripheral alcohol blocks. CONCLUSION: Pregabalin has potential anti
      neuralgia properties comparable to LTG. However, the level of patient's tolerance
      seen with PGB exceeds that with LTG. 6 months follow-up records suggest that PGB
      together with CBZ offers a more reliable pain control than with LTG.

PMID- 26225005
TI  - Awareness About Needle Stick Injures and Sharps Disposal: A Study Conducted at
      Army College of Dental Sciences.
AB  - BACKGROUND: The present study aims to assess the knowledge and attitude about
      needle stick injuries and sharps disposal. METHODS: A self designed questionnaire
      of 15 questions was handed out to 200 participants including undergraduate
      students (group 1), postgraduate students (group 2), faculty members (group 3)
      and auxiliary staff members (group 4). The data was collected and analyzed using
      Chi square test. RESULTS: Sixty-one percent of total participants reported of
      experiencing needle stick injury and 25.5 % knew that there could be several
      causes for this. Only 22 % of total population studied got the source tested.
      Immunization status of group 4 was very low and they also lacked the knowledge of
      sharps disposal and hepatitis C being spread by needle stick injuries. 57 %
      participants confirmed that there was no reporting facility and 66 % were not
      familiar with the guidelines of reporting. CONCLUSIONS: There is a definite scope
      of improvement in terms of reporting and prevention of needle stick injuries.
      There is a need to improve knowledge and awareness of dental health care workers
      about the post exposure protocol.

PMID- 26225006
TI  - Why and How Maxillofacial Disability and Impairment Due to Trauma Should be
      Quantified for Compensation: A Need for Nationwide Guidelines.
AB  - INTRODUCTION: India being is a country with different social, cultural,
      geographical and economic backgrounds; it is also grounds of rapid
      industrialization, mechanization of farming and increase in vehicular traffic
      which increases the no. of accidents and issues related to disablement and
      compensation of maxillofacial injuries. NEED FOR THE STUDY: There is no system
      available for evaluation for such injuries. The pathological condition states the
      nature of an illness but not the extent of the remaining health. Since the
      individual reacts as an integer it is important to include some appraisal of the
      physical factors influencing his work efficiency. As there is little clarity for
      disability and impairment, its separate assessment for maxillofacial injury is
      necessary. There are complex maxillofacial injuries that may cause impairment of
      sense, esthetic compromises, and functional loss. Epidemiology of craniofacial
      trauma-approximately 50 % of 12 million annual traumatic wounds treated in
      emergency rooms involve the head and neck. Being most common along with other
      injuries but is never considered for compensation. Facial region being the one
      that is the identity and factor that influences its social and emotional
      behavioral changes has not been considered. In this article various aspects have
      been considered for evaluation of compensation and disablement due to
      maxillofacial injuries.

PMID- 26225007
TI  - Comparative Analysis of the Anesthetic Efficacy of 0.5 and 0.75 % Ropivacaine for
      Inferior Alveolar Nerve Block in Surgical Removal of Impacted Mandibular Third
      Molars.
AB  - INTRODUCTION: Ropivacaine belongs to pipecoloxylidide group of local anesthetics.
      There are reports supporting the use of ropivacaine as a long acting local
      anesthetic in oral and maxillofacial surgical procedures, with variable data on
      the concentration that is clinically suitable. MATERIALS AND METHODS: A
      prospective randomized double-blind study protocol was undertaken to assess the
      efficacy of 0.5 and 0.75 % ropivacaine for inferior alveolar nerve block in
      surgical extraction of impacted mandibular third molars. A total of 60 procedures
      were performed, of which thirty patients received 0.5 % and thirty received 0.75
      % concentration of the study drug. RESULTS: All the patients in both the study
      groups reported subjective numbness of lip and tongue. The time of onset was
      longer for 0.5 % ropivacaine when compared to 0.75 % solution. 90 % of the study
      patients in 0.5 % ropivacaine group reported pain corresponding to VAS >=3 during
      bone guttering and 93.3 % patients reported pain corresponding to VAS >4 during
      tooth elevation. None of the patients in 0.75 % ropivacaine group reported VAS >3
      at any stage of the surgical procedure. The duration of soft tissue anesthesia
      recorded with 0.75 % ropivacaine was average 287.57 +/- 42.0 min. CONCLUSION:
      0.75 % ropivacaine was found suitable for inferior alveolar nerve blocks in
      surgical extraction of impacted mandibular third molars.

PMID- 26225008
TI  - Dental Caries and Periodontal Disease Status in Patients with Oral Squamous Cell
      Carcinoma: A Screening Study in Urban and Semiurban Population of Karnataka.
AB  - OBJECTIVES: To test the validity of numerous anecdotal claims of poor oral
      hygiene status being a contributory or etiology for Oral Squamous Cell Carcinoma
      (OSCC) and to isolate the microorganisms associated with oral cancer, to
      elucidate their role if any, in oral cancer. MATERIALS AND METHODS: A total of
      242 OSCC patients and 254 controls were screened. Questionnaires were used to
      inquire about the past condition of the oral health. Dental caries, oral hygiene
      status and periodontal disease status were assessed using indices. Microorganisms
      were identified by bacterial culture methods. RESULTS: Majority of cases (Group
      1) (57.85 %) never visited the dentist compared to controls (Group-2) (46.06 %).
      Group-1 brushed once in a day (93.4 %) and less often twice a day (6.6 %)
      compared to Group-2 (81.1 % and 18.9 %). There was no significant difference in
      caries experience in both groups. Teeth missing due to periodontal reasons were
      more in Group-1 (40 %) than Group-2 (26 %) (p < 0.002). Poor oral hygiene and
      increased pocket depth were seen in Group-1 than in Group-2 (p < 0.001).
      Streptococcus species (alpha-hemolytic) followed by Staphylococcus species were
      the predominant microorganisms isolated from Group-1 compared to Group-2 with (62
      % vs. 66 %) and without habits (40 % vs. 66 %). CONCLUSION: Tobacco consumption,
      lack of dental visits and infrequent brushing are significantly associated with
      increased risk of oral cancer. There seems to be no association between dental
      caries and OSCC. However, periodontal disease experience is directly proportional
      to OSCC. Increased pathogenic flora may produce carcinogenic metabolites or post
      operative infections.

PMID- 26225009
TI  - Management of Temporomandibular Disorders with Low Level Laser Therapy.
AB  - PURPOSE: To evaluate the efficacy of low level laser therapy (LLLT) in the
      treatment of temporomandibular disorders (TMD) in relation to pain intensity,
      tender points, joint sounds and jaw movements. MATERIALS AND METHODS: Twenty
      patients received 6 sessions of LLLT (3 times a week for 2 weeks) with
      semiconductive diode laser (gallium arsenide; 904 nm, 0.6 W, 60 s, 4 J/cm(2)).
      Pain intensity, number of tender points, joint sounds and active range of motion
      were assessed before and immediately after each session and after 1, 2 weeks, 1,
      3 and 6 months. RESULTS: Statistically significant results were achieved in all
      study parameters. CONCLUSION: LLLT promoted satisfactory results in reducing the
      pain intensity, number of tender points, joint sounds and improvement in the
      range of jaw motion. Hence it is an effective and efficient treatment method for
      TMDs.

PMID- 26225010
TI  - Radiodensitometric Assessment of the Effect of Pulsed Electromagnetic Field
      Stimulation Versus Low Intensity Laser Irradiation on Mandibular Fracture Repair:
      A Preliminary Clinical Trial.
AB  - PURPOSE: Closed reduction of mandibular fractures usually entails a relatively
      long period of immobilization, with the subsequent delay of rehabilitation.
      Therefore, shorter immobilization period with various approaches to protect or
      enhance bone healing have been investigated. The aim of this study was to analyze
      the effects of pulsed electromagnetic field (PEMF) and low intensity laser
      irradiation (LILI) on the fracture healing process, through radiodensitometric
      assessment of the bone callus. PATIENTS AND METHODS: Eighteen patients with
      mandibular fractures at the tooth bearing area participated in this prospective
      study. They were treated by closed reduction using maxillo-mandibular fixation
      (MMF) and were consecutively assigned into 1 of 3 groups. In group A, the
      fracture sites were exposed to PEMF for 2 h daily for 12 days. In group B, the
      fracture sites were exposed to LILI on the tenth and twelfth postoperative days
      (2 sessions of 6 min per day 2 h apart). The fracture sites in group C acted as
      controls. MMF was maintained for 2 weeks in group A and 4 weeks in groups B and
      C. The bone fracture healing was evaluated clinically by investigating the union
      of the fractured segments and radiographically using computerized densitometry.
      The union of the fractured segments was tested by manual manipulation and the
      occlusion was assessed upon removal of MMF. Standardized digital panoramic
      radiographs were performed for each patient, immediately postoperatively as well
      as at 2 and 4 weeks. The digital images were manipulated using the IDRISI
      software. A rectangular area of 10 * 15 mm was drawn along the center of the
      fracture line. The obtained densitometry values were expressed in gray levels
      from 0 to 256. The collected data were then tabulated and statistically analyzed.
      RESULTS: After releasing the MMF, the bimanual mobility test of the fractured
      segments in all patients showed stability of the segments. The preinjury
      occlusion was maintained in all patients. The postoperative radiographs of all
      patients revealed good bony alignment of the bony segments. In all groups,
      comparison between the study intervals with respect to both means and changes
      percentages of the bone density values showed insignificant differences. At 2nd
      postoperative week, the mean bone density at the fracture sites decreased by
      4.74, 6.6 and 27.89 % in groups A, B and C respectively. The period from the 2nd
      to the 4th postoperative weeks showed increase in the bone density by 1.49, 1.95
      and 14.12 % in groups A, B and C respectively. Insignificant difference was found
      between the means of bone densities of group A and B throughout the study
      intervals. On the other hand, both groups showed insignificant difference with
      group C immediately postoperative and significant increase in bone density at the
      2nd and 4th postoperative weeks. CONCLUSIONS: Short period immobilization of
      mandibular fractures for 2 weeks supplemented with PEMF is recommended. Further
      studies are needed to evaluate the efficacy of LILI as a supplement to reduce the
      mandibular fracture immobilization period.

PMID- 26225011
TI  - Aneurysmal Bone Cyst of the Jaws: Clinicopathological Study.
AB  - AIM: The aim of the present study was to analyze clinical, radiological and
      histopathological features of aneurysmal bone cysts (ABCs) of jaws. MATERIALS AND
      METHODS: Archival data from 2009 to 2012 present in the Oral Pathology Department
      was retrieved and clinicopathological features of all the cases which had been
      previously diagnosed as ABC were analyzed in detail. RESULTS: Seven cases ranging
      in age from 10 to 50 years were included, in which maximum (5/7) cases were below
      20 years. Ratio of presentation of lesion in male to female and in maxilla to
      mandible was 3:6 and 1:6 respectively. Swelling and pain were the most common
      presenting features. Variable presentation of the lesion was observed
      radiographically; although multilocular, well defined, bone expansion and
      perforation were the most common observations. Histopathological analysis
      revealed association of one case with ossifying fibroma and two cases with
      trabecular variety of juvenile ossifying fibroma. Predominance of solid variety
      was noted and other features like stroma, giant cells, nature of blood vessels,
      bone destruction and perforation and presence of any osteoid or calcified
      material was also accounted for. The current study showed association of two
      cases with trabecular variety of juvenile ossifying fibroma, which is a rare
      finding. CONCLUSION: ABCs of jaws, thus have varying patterns of presentation
      which are diagnostically challenging. A thorough examination of the
      incisional/excisional tissue is thus required to confirm the association with any
      other lesion which will affect the treatment plan for the patient.

PMID- 26225012
TI  - Comparative, Histological and Histomorphometric Analysis of Three Anorganic
      Bovine Xenogenous Bone Substitutes: Bio-Oss, Bone-Fill and Gen-Ox Anorganic.
AB  - INTRODUCTION: Anorganic bovine xenogenous grafts show the best performance as
      bone substitutes in implantodontics. Bio-Oss is the world's most widely used and
      investigated anorganic bone substitute. This article compares two anorganic
      bovine bone substitutes (Bone-Fill and Gen-Ox anorganic) with Bio-Oss. MATERIALS
      AND METHODS: Eight New Zealand rabbits were implanted with 4 titanium cylinders
      randomly filled with Bio-Oss, Bone-Fill, Gen-Ox anorganic or a blood clot. Four
      animals were sacrificed after 8 weeks; 12 weeks later, the remaining four were
      sacrificed. The contents of the cylinders were removed, cut and stained with HE
      before they were evaluated with an optical microscope. The samples were submitted
      to histomorphometry for analysis. RESULTS: The bone formation with Bio-Oss at 8
      weeks was 8.43 mm(2); at 12 weeks, it was 9.32 mm(2). The bone formation with
      Bone-Fill at 8 weeks was 7.24 mm(2); at 12 weeks, it was 9.01 mm(2). The bone
      formation with Gen-Ox anorganic at 8 weeks was 2.78 mm(2); at 12 weeks, it was
      3.02 mm(2). The bone formation with the blood clot at 8 weeks was 0.65 mm(2); at
      12 weeks, it was 0.63 mm(2). CONCLUSION: Following this model, Bone-Fill was
      comparable to Bio-Oss and superior to Gen-Ox and blood clot.

PMID- 26225013
TI  - Skeletal Relapse After Mandibular Setback in Bi Max Surgery: Intraoral Vertical
      Ramus versus Bilateral Sagittal Split Osteotomies.
AB  - OBJECTIVES: This study aimed to measure and compare the postoperative horizontal
      and vertical changes (relapse) that occur at B point and pogonion after intraoral
      vertical ramus osteotomy (IVRO) without fixation and bilateral sagittal split
      osteotomy (BSSO) with semi rigid internal fixation in bimax surgery. MATERIALS
      AND METHODS: Eleven patients with skeletal class III malocclusion mandibular
      prognathism and maxillary hypoplasia were chosen. Six cases underwent BSSO; and
      five IVRO. All patients underwent Lefort I osteotomy without genioplasty. RESULT:
      Postoperative changes (relapse) of B-point and pogonion in horizontal and
      vertical axes from 1 week post operatively (T0) to 1 year post operatively (T2)
      were assessed and the percentage of relapse of each point and each axis was
      compared. It was noted that the horizontal relapse in IVRO was 27.7 % at B point
      and 40.6 % at pogonion while, in BSSO group it was noted that the horizontal
      relapse was 28.1 % at B point and a greater number i.e., 40.9 % at pogonion.
      CONCLUSION: The percentage of horizontal relapse after IVRO without fixation is
      equal to that after BSSO with semi rigid internal fixation.

PMID- 26225014
TI  - Evaluation of a Single Dose Intravenous Paracetamol for Pain Relief After
      Maxillofacial Surgery: A Randomized Clinical Trial Study.
AB  - OBJECTIVE: The aim of this study was to evaluate, using a single dose of
      intravenous paracetamol, pain relief after maxillofacial surgery. MATERIALS AND
      METHODS: This is a controlled, randomized, uni- blind, clinical trial study to
      evaluate using a single dose of IV paracetamol for pain relief after
      maxillofacial surgery. The subjects were randomly divided into two groups with 40
      subjects in each: group I received paracetamol (Apotel)* as a single dose and
      group II received placebo. Subjects were randomly allocated according to
      randomization lists. Paracetamol was used as a single dose (20 mg/kg in 100 cc of
      normal saline which was infused for 10 min after surgery in recovery room just
      before discharging). We used a visual analogue scale to investigate pain relief
      at various times. RESULTS: Analysis of the data, did not show any significant
      difference for age, sex and weight between the treatment group and the control
      group. Pain decreased 6 h after paracetamol infusion; then it increased mildly.
      In the control group, pain severity increased after operation, then it decreased
      mildly. Results showed a correlation between duration of surgery and pain
      severity in both the groups. CONCLUSION: Paracetamol is effective on pain relief
      after maxillofacial surgeries. Operation time may be an important factor for
      induction of pain after the surgeries.

PMID- 26225015
TI  - Comprehensive Survey to Study Awareness, Knowledge and Attitude Towards HIV/AIDS
      and Hepatitis B Amongst Dental Professionals Working in Rural India.
AB  - INTRODUCTION: Thirty years into the human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS) pandemic, social and behavioral research on
      HIV/AIDS remains limited. Data on sexual behavior and AIDS-related knowledge and
      attitudes are sparse and difficult to compare. The present survey aims primarily
      towards acquiring unique source of information from health professionals in rural
      population in order to document AIDS and hepatitis B awareness. The Surveys is an
      attempt to contain a wealth of data on HIV/AIDS and hepatitis B which until now
      was not disseminated to rural audience. MATERIALS AND METHODS: Pre-formed
      questionnaire of 45 questions will be given to all dental professionals,
      practicing in rural sector, willing to participate in study. Instructions will be
      given regarding filling the questionnaire. All participants requested to complete
      the questionair with best of their knowledge and without any assistance.
      Questionnair were completed in front of author and collected back personally.
      CONCLUSIONS: The outcomes of the present study, it is clear that our efforts in
      the last two decades in spreading the knowledge about the disease have met with
      some limited success. The fact that increasing number of cases of HIV/AIDS are
      being reported from rural parts, there is certainly a need to reorient the
      ongoing training programmes towards rural population.

PMID- 26225016
TI  - Evaluation of Retro Mandibular Approach to Open Reduction and Internal Fixation
      of Condylar Fractures: A Cross-sectional Study.
AB  - PURPOSE: The present study was carried out to evaluate the usefulness of mini
      retromandibular approach on accessibility, scarring and stability in open
      reduction and internal fixation of sub condylar fractures. MATERIALS AND METHODS:
      Fifteen patients underwent open reduction and rigid fixation of middle and low
      subcondylar fractures, with mini-retro mandibular approach. RESULTS: No signs of
      infection were observed in any patient postoperatively. Surgical scar was
      imperceptible and esthetically acceptable in all the cases. Out of 15 patients,
      only one patient had discrepancy in occlusion and after 2 months satisfactory
      centric occlusion was achieved. Salivary fistula (parotid fistula) was observed
      in 3 cases within 1 week postoperatively, which was treated spontaneously with
      the use of hypertonic saline. Transient facial nerve weakness was observed in 2
      patients, in one patient it resolved in 4 weeks postoperatively and in second
      patient 3 months postoperatively. Mouth opening increased in all the patients
      with time. Average mouth opening at 1 week interval was 19.6 mm, at 2 months
      interval 28.2 mm, and after 6 months 38.33 mm suggesting that mouth opening
      gradually increased with time. At the end of 2 months postoperatively none of the
      patients had any restriction in lateral movements. At 2 months postoperatively 4
      patients had deviation but none of the patients had any deviation 6 months
      postoperatively. CONCLUSION: It is evident from the results of our study that
      open reduction and internal fixation using mini-retromandibular approach is good
      treatment option in management of mandibular condylar fractures.

PMID- 26225017
TI  - Comparison of Efficacy of Methylprednisolone Injection into Masseter Muscle
      Versus Gluteal Muscle for Surgical Removal of Impacted Lower Third Molar.
AB  - PURPOSE: To compare the efficacy, advantages and disadvantages of the use of
      preoperative injection of methylprednisolone into masseter muscle versus gluteal
      muscle to minimize postoperative swelling after the surgical removal of lower
      third molar. MATERIALS AND METHODS: A prospective randomized study was planned
      comprising of 10 subjects, undergoing elective surgery for bilateral impacted
      lower third molar removal with similar severity index. The subjects were randomly
      assigned into two groups-group I who received intrabuccal masseteric injection
      and group II who received gluteal injection of 40 mg of methylprednisolone after
      inferior alveolar nerve and long buccal nerve block (prior to the surgical
      removal of the impacted lower third molars). We evaluated the postoperative pain,
      trismus, swelling, advantages and disadvantages of the injection techniques.
      Statistical analysis was done using student t test. RESULTS: Ten patients of mean
      age 27 +/- 6 years were selected for the study including six males and four
      females. The mean age was 27 years (SD 6). The differences in measurements of
      preoperative and postoperative pain, swelling and mouth opening between group I
      and group II were not statistically significant. CONCLUSION: The study evidently
      proves that there is no statistically significant difference between the
      intrabuccal approach of masseteric injection and gluteal injection of
      methylprednisolone in terms of pain, swelling and trismus following surgical
      removal of impacted lower third molars. However, the intrabuccal approach of
      masseteric injection was found to be more convenient when compared to gluteal
      injection, for the surgeon as well as the patient. It also has an additional
      advantage of being a painless steroidal injection on an anesthetized injection
      site.

PMID- 26225018
TI  - The Anatomic Inter Relationship of the Neurovascular Structures Within the
      Inferior Alveolar Canal: A Cadaveric and Histological Study.
AB  - OBJECTIVE: The location and inter relationship of the structures of the inferior
      alveolar neurovascular bundle within the mandibular canal has not been clearly
      defined. The knowledge of the same is important while planning surgeries in the
      posterior mandible. METHODS: Eight cadaveric mandibles were dissected and
      sections were made at the distal aspect of every tooth. The inferior alveolar
      neurovascular bundle was identified and examined for the location of the inferior
      alveolar artery, vein and nerve. Hematoxylin and Eosin sections were made for
      each specimen to confirm the position of these structures. RESULTS: All the
      sections in all the specimens confirmed that a blood vessel lies superior to the
      nerve. This position appeared consistent in all the positions relative to all the
      posterior teeth. There was a variation in the bucco-lingual positioning of these
      structures relative to each other for the various mandibles. CONCLUSION: A blood
      vessel is found to always lie superior to the inferior alveolar nerve within the
      mandibular canal. Variations in the inter relationship of the structures is
      present. SIGNIFICANCE: This cadaveric study proves that all along the course of
      the neurovascular bundle, at various cross-sections studied, the inferior nerve
      is always inferior to a blood vessel. There can be great variations to the
      positioning of the structures within the neurovascular bundle in the bucco
      lingual dimension and also in the exit of the nerve in various mandibles.
      Knowledge of the location of the structures is of importance during surgical
      procedures carried out in the vicinity of these structures.

PMID- 26225019
TI  - Current Trend of Antimicrobial Prescription for Oral Implant Surgery Among
      Dentists in India.
AB  - OBJECTIVES: The aim of our study was to evaluate antimicrobial prescription
      behaviour amongst dentists performing oral implant surgery in India. STUDY
      DESIGN: Dentists performing oral implant surgery from different parts of India
      were personally approached during various national events such as conferences and
      academic meetings and information regarding their prescription habits for
      antimicrobial agents in routine oral implant surgery was collected using a
      structured questionnaire. RESULTS: Out of a total sample of 332 dentists, 85.5 %
      prescribed 17 different groups or combinations of antibiotics routinely for oral
      implant surgery in the normal healthy patient. Majority preferred the peri
      operative protocol of drug therapy (72.2 %) with variable and prolonged duration
      of therapy after surgery, ranging from 3 to 10 days. An antimicrobial mouthwash
      was routinely prescribed by all the doctors (14.5 %) not in favour of prescribing
      antimicrobials in a normal healthy patient. CONCLUSIONS: Our findings suggest
      that there is a trend of antimicrobial agent misuse by dentists performing oral
      implant surgery in India, both in terms of drugs used and the protocols
      prescribed. The majority of these dentists prescribed a variety of antimicrobial
      agents for prolonged durations routinely even in the normal, healthy patients.

PMID- 26225020
TI  - Photometric Evaluation of Soft Tissue Changes in CLP Patients: Le Fort I
      Advancement Osteotomy (ALO) Versus Anterior Maxillary Distraction (AMD).
AB  - AIM: This paper is a comparative photometric evaluation of soft tissue changes in
      patients with CLP associated with maxillary deficiency treated with conventional
      Le Fort I advancement osteotomy (ALO) and anterior maxillary distraction (AMD).
      MATERIALS AND METHODS: Twenty patients with maxillary hypoplasia associated with
      cleft lip and palate who had undergone either LeFort I osteotomy or distraction
      osteogenesis with maxillary advancement were included in this study. Frontal and
      profile photographs were used to ascertain the changes post-surgically.
      Photographs were obtained before treatment and 1 year after surgical correction
      in both groups. RESULTS: Vertical as well as horizontal changes in pronasale was
      well observed in both groups. A substantial increase in nasal parameters was
      noted in case of AMD group in comparison to ALO group. Though maxillary
      advancement was quite evident in AMD and ALO groups, a significant and consistent
      change was observed in AMD group. Significant vertical and horizontal changes
      were seen with respect to subnasale and labrale superius in AMD group.
      CONCLUSION: The hard and soft tissue changes produced by AMD by intra oral
      distractors were being evaluated so far. The results of the above studies have
      proved the excellence of AMD over conventional osteotomies. The present study
      goes hand in hand with the research outcomes till date.

PMID- 26225021
TI  - The "Rubber Band" and "Slingshot" Effects of the Posterior Airway Space in
      Mandibular Orthognathic Surgeries.
AB  - INTRODUCTION: Mandibular surgeries are the most common orthognathic procedures
      that are undertaken. The pharyngeal airway space (PAS) is influenced by the
      changes in the sagittal changes of the mandible. Mandibular advancement surgeries
      are used to an advantage in obstructive sleep apnea cases to improve the airway
      space. On the contrary, there can be a considerable decrease in the airway space
      during mandibular setback procedures. Numerous studies have been conducted to
      study the effect of changes in the PAS during mandibular procedures. However, a
      combined radiographic and endoscopic analysis of the airway space has been
      sparsely done in recent literature. MATERIALS AND METHODS: Thirty-one patients
      with mandibular discrepancies who needed mandibular surgeries were chosen. The
      assessment of PAS was done using both lateral cephalograms and endoscopic
      examination. RESULTS: As lateral cephalograms can study only the two-dimensional
      changes in the PAS, endoscopic examination both pre operatively and post
      operatively enabled the exact assessment of mandibular surgeries on the PAS. The
      PAS responds to setback mandibular surgery by modifying itself- called the
      "Rubber band" effect and in advancement surgeries as "Slingshot effect".

PMID- 26225022
TI  - Treatment of Mandibular Fractures Using Intermaxillary Fixation and Vacuum
      Forming Splints: A Comparative Study.
AB  - OBJECTIVE: The study was done to compare the clinical efficacy of vacuum formed
      splints and arch bar in treating minimally displaced mandibular fractures.
      METHOD: Forty patients were included in two groups. Group 1 was treated with
      custom made splints and group 2 with conventional arch bar. Patients were
      recalled on 3rd, 7th, 14th day and on the day of removal of the appliance.
      Periodontal status, stability of appliance and chair side time were evaluated.
      RESULTS: The mean chair side time taken by vacuum formed splint was 18.05 min and
      conventional arch bar fixation was 68.25 min. 8.3 % of patients with vacuum
      formed splints had poor oral hygiene in comparison with 25 % of patients with
      conventional arch bar. 70 % of patients with vacuum formed splints and 60 % of
      the patients with conventional arch bars were comfortable in mastication during
      treatment. CONCLUSION: Vacuum formed splints has better advantages over arch bar
      with respect to chair side time, periodontal health, patient's compliance of
      maintaining oral hygiene, mastication and speech. Vacuum formed splints avoid
      needle stick injuries. So, they can be used for intermaxillary fixation in
      minimally displaced mandibular fractures.

PMID- 26225023
TI  - Detection of Bacterial Flora in Orofacial Space Infections and Their Antibiotic
      Sensitivity Profile.
AB  - INTRODUCTION: Most odontogenic infections arise as a sequel of pulp necrosis
      caused by caries, trauma, periodontitis, etc. They range from periapical
      abscesses to superficial and deep infections in neck. Some resolve with little
      consequence and some lead to severe infections of head and neck region. The
      purpose of this study was to identify microbial flora present in orofacial space
      infection of odontogenic origin and thereby provide better perspective in
      management of odontogenic infection. MATERIALS AND METHODS: Twenty-six patients
      with space infection of odontogenic origin were selected irrespective of their
      age and gender. Pus samples were collected and processed in the microbiology
      laboratory for the growth of anaerobic and aerobic bacteria and antibiotic
      sensitivity profile. RESULTS: Demographic profile of the patients showed that
      male patients were more commonly involved and most patients fell in to the third
      and fourth decade of age groups. Most common site of involvement was
      submandibular space. Alpha hemolytic streptococci were the frequent aerobic
      bacterial isolate and among anaerobes, anaerobic streptococci followed by
      bacteroids were the major pathogens. Clindamycin, Gentamycin, Linezolid, Imipenam
      were the most effective antibiotics. 20 % of the aerobes were resistant to
      penicillin. CONCLUSION: Streptococcus species are still the commonest pathogen in
      orofacial infections of odontogenic origin. Administration of amoxicillin
      clavulanic acid combination and metronidazole followed by surgical drainage of
      abscess and extraction of infected teeth, yielded satisfactory resolution of
      infection.

PMID- 26225024
TI  - Prevalence of Various Orofacial Pain Symptoms and Their Overall Impact on Quality
      of Life in a Tertiary Care Hospital in India.
AB  - BACKGROUND: Pain is a major public health problem and is the most commonly
      reported symptom of oral and dental disease that has a significant impact on both
      individual and community. The present study was prevalence of various orofacial
      pain symptoms and their overall impact on the quality of life in a tertiary care
      hospital. MATERIALS AND METHODS: This study was carried out in the outpatient
      department of the Government Dental College and Research Institute, Bangalore.
      The severity of the chronic orofacial pain symptoms was assessed using the
      Chronic Pain Grade Questionnaire by Von Korff. RESULTS: The results showed that
      toothache (57.6 %) was the most commonly reported symptom and burning mouth
      sensation (6.4 %) was the least commonly reported. Majority of the patients had
      grade 3 level of pain-related disability (34.8 %) followed by grade 2 (26.8 %),
      grade 1 (22.4 %) and grade 4 levels (16 %). The mean pain intensity was reported
      to be more among females and maximum among patients with facial pain. CONCLUSION:
      The present study demonstrated that orofacial pain symptoms have a significant
      impact on the patients suffering from it. Therefore, proper measures should be
      taken for the management of the patients with these symptoms and associated
      conditions.

PMID- 26225025
TI  - Evaluation of Vertical Bone Gain Following Alveolar Distraction Osteogenesis in
      the Anterior Edentulous Mandible: A Clinical Study.
AB  - AIM AND OBJECTIVES: To calculate the gain in bony height and volume of the
      distracted upper segment using an extraosseous unidirectional device to improve
      the retention of the future prosthesis. MATERIALS AND METHODS: Ten cases with
      completely or partially edentulous but severely or considerably resorbed anterior
      mandibles were managed by vertical alveolar distraction osteogenesis. All the
      patients were evaluated preoperatively, intraoperatively and post-operatively for
      various parameters clinically and radiographically i.e. on OPG, lateral
      cephalogram and on CT scan, at different time intervals. In all cases there was
      increase in vertical bone height. RESULTS: The study showed mean vertical bone
      gain (VBG) on OPG as 8.2 mm. The mean VBG on lateral cephalogram was 8.1 mm. The
      mean VBG on CT scan at right canine was 8.35 mm, at left canine was 8.2 mm and at
      midline was 8.27 mm. CONCLUSION: Alveolar distraction osteogenesis is a
      predictable method for restoring alveolar ridges prior to implant placement or
      prosthesis. Distraction osteogenesis is ideally suited for recreating missing
      tissue in the anterior esthetic zone by increasing vertical bone height as well
      as good width and soft tissue growth.

PMID- 26225026
TI  - Closure of Anterior Palatal Fistula by Tongue Flap: A Prospective Study.
AB  - AIM: To check the efficacy of dorsal tongue flap in closure of anterior palatal
      fistula without using any fixation devices. MATERIAL AND METHOD: It is a
      prospective study in which 20 patients of anterior palatal fistula, larger than 5
      mm, attending the outpatient department of oral and maxillofacial surgery,
      Genesis Institute of Dental Sciences and Research, Ferozpur over a period of 5
      years (from November 2005 to January 2011) were included. The surgical treatment
      was divided into 2 stages-raising of the flap on the tongue and transfer of the
      flap from the dorsum of the tongue to fistula site and then separation of flap
      and its adjustment at the site of defect after an interval of 3 weeks minimum.
      Follow-up was done for 3 and 6 months. RESULT: Successful closure was achieved in
      90 % of the cases. 80 % patients experienced decrease in hypernasality. In none
      of the cases decrease in size of tongue, loss or change in taste sensation,
      difficulty in speech, difficulty in swallowing or bulkiness of flap was observed.
      CONCLUSION: The results obtained during the course of this study strongly support
      the method used to close the anterior palatal fistula. It is concluded that the
      dorsal tongue flap is the highly successful method without the need of additional
      fixation devices in closure of anterior palatal fistula.

PMID- 26225028
TI  - Evaluation of Elongated Styloid Process in Patients with Oral Submucous Fibrosis
      Using Panoramic Radiographs.
AB  - INTRODUCTION: Oral submucous fibrosis (OSF) is an insidious disease affecting the
      oral cavity, pharynx, and upper digestive tract. It is characterized by a
      juxtaepithelial inflammatory reaction followed by fibroelastic change in the
      lamina propria and associated epithelial atrophy. Higher levels of TGF-beta
      present in patients with OSF could be responsible for impetus to remnants of
      Reichert's cartilage present in styloid complex leading to partial or complete
      ossification of associated ligaments. So, a study was conducted to evaluate the
      elongation of the styloid process in patients with OSF by using panoramic
      radiographs. MATERIALS AND METHODS: Panoramic radiographs of patients with OSF
      were studied from 2007-2011. The apparent lengths of styloid process were
      measured with the help of divider and steel metric ruler. The length of the
      styloid process and/or ossification of stylomandibular ligaments which were
      longer than 30 mm were considered. RESULTS: Out of 47 patients, 35 patients (34
      males & 1 female) met the inclusion criteria. Eleven patients (31.4%) were found
      to have elongated styloid processes which included 10 male patients and 1 female
      patient. CONCLUSION: It had been estimated that between 2 % and 4% of the general
      population presents radiographic evidence of an ossified portion of the styloid
      complex. The high incidence of elongation of styloid process (31.4 %) in patients
      with oral submucous fibrosis highlights that progressive OSF might have some
      influence on elongation of styloid process.

PMID- 26225027
TI  - Management of Cleft Maxillary Hypoplasia with Anterior Maxillary Distraction: Our
      Experience.
AB  - Maxillary hypoplasia is a common developmental problem in cleft lip and palate
      deformities. Since 1970s these deformities have traditionally been corrected by
      means of orthognathic surgery. Management of skeletal deformities in the
      maxillofacial region has been an important challenge for maxillofacial surgeons
      and orthodontists. Distraction osteogenesis is a surgical technique that uses
      body's own repairing mechanisms for optimal reconstruction of the tissues. We
      present four cases of anterior maxillary distraction osteogenesis with tooth
      borne distraction device-Hyrax, which were analyzed retrospectively for the
      efficacy of the tooth borne device-Hyrax and skeletal stability of distracted
      anterior maxillary segment. 

PMID- 26225029
TI  - Retrospective Analysis of Ossifying Fibroma of Jaw Bones Over a Period of 10
      Years with Literature Review.
AB  - OBJECTIVE: The purpose of this retrospective analysis is to document and discuss
      the features, treatment rendered and result of 25 histologically proven cases of
      ossifying fibromas of jaw bones operated by a single surgeon over a period of 10
      years. MATERIALS AND METHODS: The records of ossifying fibroma were obtained from
      the archives of Oral and Maxillofacial Surgery at Maulana Azad Institute of
      Dental Sciences (MAIDS) from 2001 to 2011. Only those cases were included in the
      study where definitive surgery was performed based on clinical, radiological &
      histopathological features. RESULTS: Twenty-five patients were analyzed with a
      final diagnosis of ossifying fibroma comprising of 14 males (56 %) and 11 females
      (44 %). The age range was 11-45 years with a mean of 24.12 years. Mandible was
      involved in 72 % and maxilla in 28 % cases with a predominance of mandibular
      posterior [19 (76 %)] cases. The study showed similar findings in regard to
      clinical, radiographic & histological features of ossifying fibroma as compared
      to other studies. It also showed that the treatment rendered in the form of
      eneucleation, curettage or resection of the lesion depending on its stage and
      extent were adequate, as no recurrence has been reported till date. CONCLUSION:
      Enucleation is preferred in small and well demarcated lesions. Curettage should
      be done in relatively large lesions with ill defined borders, not involving basal
      bone of mandible or cortical perforation. Resection should be reserved for
      aggressive and extensive cases with involvement of basal bone or perforation of
      cortices.

PMID- 26225030
TI  - Reconstruction of Nasal Cleft Deformities Using Expanded Forehead Flaps: A Case
      Series.
AB  - INTRODUCTION: Reconstruction of the nasal clefts is a challenging task
      considering the nasal anatomic complexity and their possible association with
      craniofacial defects. The reconstruction of these defects needs extensive amounts
      of soft tissue that warrant the use of forehead flaps. Often presence of cranial
      defects and low hairline compromise the amount of tissue available for
      reconstruction warrenting tissue expansion. AIM: To evaluate the efficacy of
      tissue expansion in reconstruction of congenital nasal clefts. SUBJECTS AND
      METHODS: 9 patients with congenital nasal clefts involving multiple sub units
      were taken up for nasal reconstruction with expanded forehead flaps. The average
      amount of expansion needed was 200 ml. The reconstruction was performed in 3
      stages. RESULTS: Expanded forehead flaps proved to be best modality for
      reconstruction providing the skin cover needed for ala, columella and dorsum with
      minimal scarring at the donor site. CONCLUSION: Expansion of the forehead flap is
      a viable option for multiple sub unit reconstruction in congenital nasal cleft
      deformities.

PMID- 26225031
TI  - Total Alloplastic Temporomandibular Joint Reconstruction for Management of TMJ
      Ankylosis.
AB  - INTRODUCTION: Temporomandibular joint (TMJ) ankylosis involves the fusion of the
      mandibular condyle to the glenoid fossa, the skull base. The dilemma with regards
      to treatment planning whether distraction is done before gap arthroplasty or as a
      simultaneous procedure or after gap arthroplasty is still a controversy. In an
      attempt to carry out both the procedures simultaneously there is loss of vector
      control of the distal segment and the risk of pseudoarthrosis at the osteotomy
      site. This combined problem could be overcome by the use of total alloplastic
      joint prosthesis which offers a firm posterior stop for the proximal segment and
      negates aggressive physiotherapy. MATERIAL AND METHODS: The reference literatures
      were retrieved from Pub Med and Science Direct database. Three case reports of
      bilateral recurrent TMJ ankylosis successfully treated with custom made total TMJ
      by the authors are illustrated. CONCLUSION: The purpose of this article is to
      review the world literature on various alloplastic joints available for TMJ
      reconstruction and to introduce our indigenous total joint prosthesis in the
      management of recurrent ankylosis.

PMID- 26225032
TI  - Randomised Comparative Study on Propofol and Diazepam as a Sedating Agent in Day
      Care Surgery.
AB  - OBJECTIVE: The study was conducted to assess the usefulness by qualitative
      comparison between the two intravenous sedative drugs, Diazepam and Propofol and
      to provide sedation in apprehensive and uncooperative patients undergoing day
      care oral surgical procedures. METHODS: The present study was conducted on 20
      adult patients, 10 in each group (Propofol and Diazepam) irrespective of age and
      sex. Intravenous sedation of Propofol compared with Diazepam in terms of onset of
      action, recovery, and anterograde amnesia, patient co-operation, surgeon's
      convenience and side effects and other parameters. RESULTS: Propofol was found to
      be the superior sedating agent compared to Diazepam, having rapid onset and
      predictability of action, profoundness of amnesia and a faster recovery period,
      offering advantages of early patient discharge and better patient compliance.
      CONCLUSION: Propofol was found to be an ideal sedating agent in day care oral
      surgical procedures.

PMID- 26225033
TI  - A Prospective Study on Management of Mandibular Angle Fracture.
AB  - PURPOSE: To evaluate the results of management of mandibular angle fracture by
      open reduction and internal fixation using single non compression miniplate via
      transbuccal, intraoral or extraoral approaches. PATIENTS AND METHODS: In this
      prospective study, 30 patients were randomly selected regardless of age, sex
      requiring open reduction and internal fixation of non comminuted angle fracture
      with/or without other associated fractures of the mandible. All the patients were
      operated under general anaesthesia following routine haematological, biochemical,
      general physical examination and routine radiographic examination. Patients were
      randomly distributed into 3 groups namely: (1) intraoral, (2) transbuccal, and
      (3) extraoral groups depending on the surgical approach used for open reduction
      and internal fixation of fracture of the angle of mandible. In the intraoral
      group (12 patients), angle fracture was approached through the intraoral
      vestibular incision similar to sagittal split incision. In the transbuccal group
      (8 patients), angle fracture was approached through the intraoral vestibular
      incision and transbuccal stab incision for screw fixation via trochar. In the
      extraoral group (10 patients), angle fracture was approached through the Risdon's
      submandibular incision. In all the patients, fractures were reduced with upper
      and lower Erich's arch bar fixation as means for IMF intraoperatively. In all the
      patients, fracture of the angle of the mandible was fixed with single non
      compression 2.5 mm, 4 holed with gap stainless steel miniplate and 6/8 mm
      monocortical screws. All patients were followed up for minimum of 6 months to
      maximum of 24 months. RESULTS: Complications were relatively minor such as
      paresthesia (on average 26.7 % first post-operative day which was gradually
      improved and on average after 1 month was 3.3 %), mild to moderate occlusal
      discrepancies (on average 36.7 %) which needed the post-operative intermaxillary
      fixation with elastics for 1-2 weeks, infection (20 % on average) was mild to
      moderate which was managed with antibiotic therapy and/or incision and drainage
      except in one case, plate removal was done under general anaesthesia (extraoral
      group) because of recurrent infection. Post-operative pain was mild to moderate
      (mean VAS score pre operative-6.17, post-operative 1 week-1.63) which was managed
      with analgesics. Mouth opening was recorded in all patients which was on average
      20.98 mm preoperatively which improved to 40.57 mm after 1 month. CONCLUSION: The
      use of a single non compression miniplate for fractures of the angle of the
      mandible is a simple, reliable technique with relatively rare major complications
      and few minor complications irrespective of the surgical approach used for the
      open reduction.

PMID- 26225034
TI  - A Comparative Pilot Study to Evaluate the Adjunctive Role of Levosulpride with
      Trigger Point Injection Therapy in the Management of Myofascial Pain Syndrome of
      Orofacial Region.
AB  - PURPOSE: To evaluate the effect of therapy with levosulpride combined with
      conventional trigger point injection therapy in terms of pain and depression in
      the chronic myofascial pain syndrome patients. MATERIALS AND METHODS: This was a
      comparative prospective study in which subjects with at least one trigger point
      and symptom duration of at least 3 months were recruited and randomized into two
      groups. Group A subjects received trigger point injections with 0.5 % bupivacaine
      and tablet levosulpride and group B received trigger point injections and a
      placebo. Subjects were assessed for pain with visual analog scale (VAS) and
      depression with Beck's depression inventory (BDI) at the follow-up periods of 1,
      4, 6 and 12 weeks. The treatment effect was measured in terms of mean difference
      of BDI and VAS scores at various studied intervals from the baseline values.
      RESULTS: The sample was composed of 15 subjects with 8 in group A (6 females and
      2 males, with a mean age of 41.88 +/- 15.13 years, disease duration of 12.37 +/-
      16.11 months) and 7 in group B (6 females and 1 male, with a mean age of 43.86 +/
      12.34 years, disease duration of 9.64 +/- 9.34 months). The mean baseline VAS
      score and BDI score was 6.75 +/- 1.03 in group A and 6.86 +/- 1.06 in group B and
      24.25 +/- 10.20 in group A and 24.43 +/- 11.16 in group B respectively. The mean
      difference of VAS scores at 12th week interval from the baseline values was
      highly significant. Although the mean difference of VAS scores at all the other
      intervals and mean difference of BDI scores at all the intervals was
      statistically nonsignificant, there was improvement in the mean differences at
      all the follow-up intervals in terms of both pain as well as depression.
      CONCLUSIONS: The combined therapy with conventional trigger point injection and
      levosulpride as antidepressant significantly reduce pain and depression in the
      study subjects suffering from chronic myofascial pain with moderate to severe
      depression in the orofacial region.

PMID- 26225035
TI  - Intraoral Periapical Radiographs with Grids for Implant Dentistry.
AB  - There are ample modern diagnostic imaging tools available, but the affordability,
      availability and radiation exposure remains the concern. Intraoral periapical
      radiographs (IOPAR) are widely used for the preoperative planning and evaluation
      for most minor oral surgical procedures owing to it simplicity, significantly
      lower cost, less radiation exposure and easy availability in a dental clinical
      set-up. Using these radiographs with a grid aids in increasing the accuracy of
      the linear measurements for the treatment planning. 

PMID- 26225036
TI  - Protocol for Removal of Third Molar Root Tips from the Inferior Alveolar Canal
      Crossing the line.
AB  - INTRODUCTION: The safe removal of third molars involved with the inferior
      alveolar canal (IAC) has been an area of concern since long. Many times we
      hesitate for the removal of third molars, fearing injury to the inferior alveolar
      nerve. MATERIALS AND METHODS: The authors here describe a simple technique which
      can be used to remove third molars showing evidence of proximity to IAC on
      presurgical radiographic evaluation, as well as those root tips which, during
      removal, accidentally enter the IAC space. CONCLUSION: A step-by-step protocol is
      presented along with necessary precautions during the operative procedure.

PMID- 26225037
TI  - An Inexpensive Suturing Training Model.
AB  - INTRODUCTION: Demonstrations and training on live-subjects are not always the
      optimal means of introducing the students to minor oral surgery. Hence, the use
      of teaching models permit the students to handle the surgical instruments in a
      limited field under a semi-realistic circumstance and also helps in developing
      psychomotor skills in an non stressed situation. One among the competent exercise
      in oral surgery is suturing. Though there exist a variety of commercially
      available suturing training models, cost factor restrain their acquirement in few
      units. METHODS & MATERIALS: This paper describes the construction of a simple and
      cost-effective suturing model for preclinical training. The construction of this
      model requires an orange peel, putty impression material and plaster of paris.
      This suturing model can be created in ten minutes. CONCLUSION: This model can be
      constructed by the students with minimal effort and low cost in order to practice
      suturing.

PMID- 26225038
TI  - The "Red Line" Conundrum: A Concept Beyond Its Expiry Date?
AB  - Introduction George Winter attempted to assess the depth and difficulty of
      extracting impacted mandibular wisdom molars by describing three imaginary lines
      drawn on an intra-oral radiograph. Of these lines, the red line is the only one
      which is measured and great importance is attached to its actual length. Method
      The authors of this short paper describe the difficulty in drawing this red line
      accurately through examples. Conclusion The authors believe that Winter's lines
      and their interpretation are only of historical value and have no place in
      contemporary texts on oral surgery. 

PMID- 26225039
TI  - Surgical Interventions in Oral Submucous Fibrosis: A Systematic Analysis of the
      Literature.
AB  - BACKGROUND: Oral submucous fibrosis (OSMF) is a potentially malignant disorder of
      the oral cavity. The surgical management of this condition involves excision of
      the fibrotic bands and interpositional grafts to retain the increased oral
      opening. Various procedures and graft material have been utilised with differing
      success rates. OBJECTIVES: The present review aims to collate and analyze from
      world literature the different modalities utilized in the surgical management of
      OSMF. The reasons for the choice of a particular surgical procedure, the study
      protocol, the average follow-up period and the results were scrutinized.
      MATERIALS AND METHODS: The PRISMA protocol was followed for the systematic
      review. Search engines and medical databases like Ovid, Medline, Pubgate,
      Researchgate, PubMed, Google etc. were tapped for information related to the
      subject. The search words "OSMF", "surgical interventions in OSMF", "flaps and
      grafts in treatment of OSMF" were employed for retrieval of data. An analysis of
      the treatment modalities, the reason for the selection of a particular modality,
      the organization of the sample selection and the follow-up periods including the
      proclaimed success rates was done. RESULTS: The review resulted in a total of 56
      articles on the subject from the sources mentioned above. A total of 995
      surgically treated cases were included in the analysis. Interestingly the review
      revealed very few controlled clinical trials, most being random trials on
      surgical procedures in small groups of patients with very short follow up
      periods. The choice of procedure seems to be determined entirely by the
      preference of the operator/s. CONCLUSIONS: There exist no definite protocols for
      the adoption of a particular treatment mode in OSMF. Adequate documentation and
      follow up need to be established to statistically analyse the results and
      proclaimed successes of various treatment modalities.

PMID- 26225040
TI  - Giant Parapharyngeal Space Pleomorphic Adenoma of the Deep Lobe of Parotid
      Presenting as Obstructive Sleep Apnoea: A Case Report & Review of the Diagnostic
      and Therapeutic Approaches.
AB  - INTRODUCTION: Salivary gland tumours constitute about less than 4 % of all head
      and neck tumours. Pleomorphic adenoma, also called benign mixed tumour, is the
      most common tumour of the salivary glands. About 80-90 % of these tumours occur
      in the major salivary gland mainly parotid gland and 10 % of them occur in the
      minor salivary glands. AIMS AND METHODS: Aim of this case report is to discuss
      the unique case of giant parotid pleomorphic adenomas arising in the deep lobe
      involving the parapharyngeal space and difficulty in respiration at sleep during
      nights repoted at this institute. The patient was undergoing treatment for
      obstructive sleep apnea syndrome when she reported at this institute for
      disturbed sleep. Diagnosis was based on computed tomography scan and magnetic
      resonance imaging and cytology by means of fine needle aspiration biopsy.
      CONCLUSION: An exhaustive pre-operative diagnostic algorithm is mandatory before
      approaching such lesions involving parapharyngeal space. Fine needle aspiration
      biopsy is, in our opinion, mandatory to avoid histological surprises. The
      surgical approach varies according to the location of the tumour and should
      provide excellent visibility with wide surgical exposure to secure local
      neurovascular structures.

PMID- 26225041
TI  - Rising from Plagiarising.
AB  - Amongst the various forms of scientific misconduct, plagiarism has become
      increasingly prevalent in today's scientific process. Plagiarism is copying
      another author's ideas or words and portraying them as your own. Inclusion of
      another source's contents without giving credit to the source results in this
      unethical practice. Text derived directly from a source must always be put under
      quotation marks. Decreased awareness about plagiarism and what exactly
      constitutes it results in unintentional plagiarism. Plagiarism can be that of the
      ideas in which the author projects others' ideas as his own. It can also be that
      of the text also known as word to word plagiarism. Mosaic plagiarism is another
      form. Various guidelines formulated by esteemed scientific bodies such as World
      Association of Medical Editors, Committee on publication Ethics have provided an
      insight to authors, editors, publishers and peer reviewers into the practice of
      ethical writing. By understanding the true essence of plagiarism and following
      strict guidelines, it is certainly possible to avoid plagiarism. Various
      softwares are available to detect plagiarism. These softwares have a wide
      database which is scanned to reveal any kind of malpractice. If detected, it can
      have grave consequences causing not only retraction of the article but also loss
      of dignity. Failure to detect plagiarism reflects negatively on a journal.
      Originality is the true essence of any research or scientific paper. Any
      violation of this fact is an unforgivable offence. Thus, this review article
      attempts to cover the meaning, types, risks and ways to avoid plagiarism. 

PMID- 26225042
TI  - Keratocystic Odontogenic Tumours: Etiology, Pathogenesis and Treatment Revisited.
AB  - INTRODUCTION: Among the pathological entities that affect the maxillofacial
      region, Keratocystic odontogenic tumour has been subject to a lot of debates,
      controversies and speculations because of its diverse nature and high recurrence
      rates. MATERIALS AND METHODS: The authors conducted a search in English
      literature using the following keywords; "Odontogenic keratocyst" and
      "Keratocystic odontogenic tumour". The aim of the paper was to review all aspects
      of the entity, including etiology, pathogenesis, clinical and radiological
      manifestations, growth potential, recurrence and treatment modalities.
      CONCLUSION: The controversial nature of the pathology not withstanding, there is
      in general a broad consensus on treating the entity conservatively with emphasis
      on a long term review.

PMID- 26225043
TI  - "Vanishing Bone Disease" in Maxillofacial Region: A Review and Our Experience.
AB  - Vanishing bone disease (VBD) is a rare disease of unknown etiology which is
      characterised by progressive replacement of bony framework by proliferation of
      endothelial lined lymphatic vessels. It has been given numerous names like
      massive osteolysis, Gorham's disease, phantom bone disease, and progressive
      osteolysis. It has no age, sex or race predilection. It may involve single or
      multiple bones and spread of the disease does not respect the relevant joint as
      boundary. The first report of the disease was published around two decades back
      but the mysterious nature of its etiology and ideal management strategy has still
      not been completely unfolded. The disease may functionally or aesthetically
      effect the patient and also has the potential to be life threatening. The first
      case of VBD in maxillofacial region was reported by Romer in 1924, Handbuch der
      speziellen pathologischen Anatomie and histology, Springer, Berlin. Since then,
      there have been few case reports of the same in maxillofacial region. We present
      a review of cases of VBD in maxillofacial region reported in literature along
      with our experience of a case. 

PMID- 26225044
TI  - Keratocystic Odontogenic Tumor (KCOT/OKC)-Clinical Guidelines for Resection.
AB  - PURPOSE: There is no clinical consensus for the treatment of Keratocystic
      Odontogenic Tumor (KCOT). KCOTs are regarded as benign aggressive tumors and
      resection is usually considered as a last option. We review the clinical
      indications for resection based on a case series. METHODS: This is a
      retrospective study of patients with KCOT treated in a single unit over 17 years.
      Eighty patients were identified, of which 12 (15 %) underwent resection. The
      remaining 68 patients were managed by enucleation and curettage, enucleation with
      peripheral ostectomy, or decompression with secondary enucleation. Data extracted
      includes gender, age, race, location, previous treatment for the lesion, surgery
      and outcome/follow up. RESULTS: Twelve patients treated by resection were
      identified. The location in the ten benign resected KCOTs was either the
      mandibular ramus or the posterior maxilla. All mandibular KCOTs exhibited
      perforation of the lingual plate and involvement of the pterygoid musculature.
      Seven of the ten cases were recurrent KCOTs and three had no prior treatment. Two
      had malignant changes in the KCOT and were also resected. CONCLUSION: The primary
      reason for resection of KCOT was involvement of the pterygoid muscles. The
      presence of malignant change was a separate indication for resection.

PMID- 26225045
TI  - Costochondral Graft as Interpositional material for TMJ Ankylosis in Children: A
      Clinical Study.
AB  - ABSTRACT: TMJ ankylosis is one of the most disruptive anomaly that affects the
      masticatory system. The inability to move the mandible has significant functional
      ramification, such as the inability to eat a normal diet. Additionally, speech is
      affected, making it difficult for some individuals to communicate and express
      themselves to others. As there are several biologic and anatomic similarities to
      the mandibular condyles, autogenous costochondral grafts have been considered to
      be the most acceptable tissue for temporomandibular joint reconstruction. In
      addition donor site complications are infrequent and regeneration of the rib
      usually occurs within a year post operatively in children. AIM: The aim of this
      study was to evaluate the function of costochondral grafts to replace the
      mandibular condyles and to assess the position, growth, overgrowth, function,
      success, failure and resorption of costochondral grafts. MATERIALS AND METHODS:
      Ten TMJ ankylosis patients were operated in the Department of Oral and
      Maxillofacial Surgery at Institute of Dental Sciences, Bareilly. Out of the 10
      cases 6 were male patients and 4 female patients in age group of <=14 years; of
      which 8 patients were of unilateral TMJ ankylosis and 2 were of bilateral TMJ
      ankylosis. All ten patients underwent interpositional gap arthroplasty with
      reconstruction of the condyle by costochondral graft. RESULTS: All patients with
      costochondral grafts had improved mandibular symmetry and growth with adequate
      mouth opening. CONCLUSION: This study indicates that using costochondral grafts
      to reconstruct TMJ ankylosis in children provides a good result.

PMID- 26225046
TI  - The Need for Lateral Piriform Rim Augmentation in Patients with Unilateral Cleft
      Lip/Palate During Alveolar Cleft Bone Grafting.
AB  - BACKGROUND: Alveolar bone grafting in unilateral cleft lip/palate (CLP) patients
      can improve nasal symmetry and facial esthetic. In some cases lateral piriform
      hypoplasia cannot be compensated by soft tissue thickness of the face,
      necessitating onlay bone grafting. This study was designed to estimate the
      proportion of patients among unilateral CLP patients requiring this procedure.
      MATERIALS AND METHODS: In a retrospective study, unilateral CLP patients with
      severe paranasal deficiency, who were managed by paranasal augmentation with
      cortico-cancellous bone graft during the alveolar cleft bone grafting, were
      included. RESULTS: From 85 unilateral CLP patients treated from 2005 to 2011 in
      the Oral and Maxillofacial Surgery Department, Mashhad University of Medical
      Sciences, fourteen patients were treated with lateral piriform augmentation
      technique. Mean age of the patients at the time of operation was 16 +/- 4.8
      years. Follow-up period was 2-6 years. CONCLUSION: Concomitant alveolar bone
      grafting and lateral piriform augmentation is needed at least in 16.5 % of
      unilateral CLP patients.

PMID- 26225047
TI  - Efficacy of Simvastatin in Bone Regeneration After Surgical Removal of Mandibular
      Third Molars: A Clinical Pilot Study.
AB  - INTRODUCTION: Simvastatin, a common cholesterol-lowering drug that inhibits
      hepatic hydroxymethylglutaryl coenzyme A reductase, the rate-limiting enzyme in
      the mevalonate pathway, increases expression of the BMP-2 gene and thus promotes
      bone regeneration. MATERIALS AND METHODS: A study was conducted in mandibular
      third molar sockets to study the efficacy of the drug by implanting it into
      sockets (experimental group) and observations were made over 3 months to compare
      the healing with the (control group). CONCLUSION: The results showed faster
      regeneration of the bone in the simvastatin site using the gray level histogram
      values.

PMID- 26225048
TI  - The Effects of Topical Hemocoagulase Solution on the Healing Process of Post
      extraction Wounds: A Split Mouth Design.
AB  - OBJECTIVES: To evaluate the effects of topical hemocoagulase on intra-oral
      extraction sockets and impact on the healing process as well as to produce a
      clinico-histological healing score. STUDY DESIGN: This prospective study compared
      two extraction sites in each subject. One site received topical hemocoagulase
      while other site did not receive it. Both the sites were chosen in the same
      patient and extraction was done at separate intervals. The biopsy was done on a
      random basis with the pathologist being blinded to the study. Clinical evaluation
      was done on days 7, 14 and 21. Biopsy was done either on days 7 or 14 for the
      case as well as for the control. A clinical as well as histological score was
      developed and the healing was assessed. Statistical analysis was done using
      Wilcoxon signed rank test and p value <= 0.05 was considered significant and z
      score was also calculated. RESULTS: The clinical score did not show any
      statistical significance. The histological total score on day 14 and combined
      overall analysis of days 7 and 14 showed statistical significance. There was an
      increased incidence (n = 4) of osteoid formation in the hemocoagulase group on
      day 14. CONCLUSION: The application of hemocoagulase may improve and accelerates
      the process of wound healing in extraction sockets.

PMID- 26225049
TI  - A Study on the Influence of the Osteotomy Slope on Bony Changes after Advancement
      Genioplasty.
AB  - INTRODUCTION: The slope of the osteotomy used for the genioplasty dictates the
      vertical change. The horizontal bony changes after advancement genioplasty are
      not identical to the intercortical bony changes, because the variety of osteotomy
      slopes result in different vertical changes. MATERIAL AND METHODOLOGY: Ten of
      these patients had additional osteotomies as follows: five maxillary, three
      mandibular and two both maxillary and mandibular. Pre-operative and post
      operative (at least 6 months) lateral cephalograms were retrospectively analyzed
      to assess horizontal and vertical movements of the chin. The following landmarks
      were used, Hard tissue pogonion (Pog), Occlusal plane (OPL), Menton (Me), Menton
      plane (MePL). The following parameters were calculated: DeltaH = H-H, DeltaV = V
      V, The ratio between DeltaH and DeltaV equals tangent alpha, Calculated alpha =
      inverse tangent alpha . RESULTS: The Mean Horizontal bony movements was 3.75 mm
      (SD 1.4 mm, range -6 to 15 mm). The Mean Vertical bony movements was 1.4 mm (SD
      0.8 mm, range 0.5-2 mm). The Mean Measured Osteotomy slope angle was 82.2 (SD
      7.4, range 75-91). The Calculated Mean Slope Angle based on the DeltaH/DeltaV
      ratio was 82.3 (SD 7.0, range 74-95). DISCUSSION: The slope of the osteotomy used
      for the genioplasty dictates the vertical change. The osteotomy slope angle was
      defined as the angle between the osteotomy and a line perpendicular to the
      occlusal plane. The measured angle was compared with the calculated angle deduced
      from the horizontal and vertical genial post-operative changes.

PMID- 26225050
TI  - Reliability of Incision Biopsy for Diagnosis of Oral Verrucous Carcinoma: A
      Multivariate Clinicopathological Study.
AB  - INTRODUCTION: Studies have reported 20 % of conventional squamous cell carcinoma
      in patients with verrucous carcinoma (VC), later these cancers were termed as
      hybrid VC. It is important to distinguish both while planning treatment since
      hybrid VC requires addressing regional lymphatics in addition to respective
      surgery. Information on odds of missing the foci of invasion on routine incision
      biopsy might be useful in this regard. PATIENTS AND METHODS: Records of all the
      patients surgically treated for oral cancer from Jan 2010 to Oct 2013 in a
      Tertiary Cancer Centre was analyzed. Patients diagnosed with primary VC or
      Verrucous Hyperplasia on incision biopsy were included in the study. Proportion
      of patients undiagnosed for invasive component on incision biopsy was calculated,
      multivariate analysis of the sample was performed to find associated cofounders.
      RESULTS: Fifty-five patients who reported with the diagnosis of VC (n = 53) or
      Verrucous Hyperplasia (n = 2) on incision biopsy were included in the study.
      Twenty-seven were diagnosed as VC and 28 as hybrid VC after excision. This
      corresponded to 51 % (n = 28) of cases missing invasive component on incision
      biopsy. VC was significantly more commonly seen in lip and in buccal mucosa,
      hybrid VC was more commonly seen in tongue and gingiva and this association was
      statistically significant (p = 0.031) in our study. CONCLUSION: Incision biopsy
      is extremely unreliable to diagnose and differentiate oral Hybrid VC from VC or
      Verrucous Hyperplasia. Caution is required while planning treatment of these
      patients regarding possibility of presence of conventional squamous cell
      carcinoma within these tumors.

PMID- 26225051
TI  - Reconstruction of Orbital Floor Fractures with Autogenous Bone Graft Application
      from Anterior Wall of Maxillary Sinus: A Retrospective Study.
AB  - INTRODUCTION: Orbital wall fracture implies a situation where disruptions of the
      walls or floor have occurred. It is a blowout type fracture where bone fragments
      with torn periosteum are pushed outside of the original bony orbit. There is no
      intact bone even near the defect area except the thin bone rim surrounding the
      blowout fracture. The purpose of this defect repair is to support orbital
      contents, free entrapped tissue, and, especially, restore the original orbital
      volume. MATERIAL AND METHODS: Ten patients (seven males and three females) who
      underwent repair of orbital floor factures with maxillary sinus bone grafts were
      included in this study. Surgical procedure for harvesting graft and its fixation
      was almost same in all operated cases. CONCLUSION: The collection in the
      maxillary sinus due to fracture of floor of orbit, blood and bony fragments
      collected in the maxillary sinus can be easily drained and removed after removal
      of anterior wall of maxillary sinus and through the same approach you can reduce
      the floor of orbit manually to the proper position which helps to decease the
      orbital floor defect.

PMID- 26225052
TI  - Periotome as an Aid to Atraumatic Extraction: A Comparative Double Blind
      Randomized Controlled Trial.
AB  - AIM: The aim of this study was to evaluate the efficacy of periotomes in single
      rooted nonsurgical tooth extractions. MATERIALS AND METHODS: A double blind,
      randomized controlled clinical trial of 100 patients requiring nonsurgical single
      rooted tooth extractions was performed. The subjects were randomized into the
      experimental group (underwent extractions with periotome and conventional
      extraction forceps) or into the control group (subjects underwent extractions
      using periosteal elevator and conventional extraction forceps). Pain was assessed
      using visual analogue scale all throughout 7 days postoperatively. Gingival
      laceration, duration of surgery, number and frequency of analgesics consumed and
      complications (if present) were also noted. RESULTS: On inter-group comparison,
      all the parameters were statistically significant in control group (p < 0.05).
      Also on pre and post-operative inter-group comparison, statistically significant
      pain reduction was noted in experimental group (52.8 %) whereas pain increased in
      control group (65 %). CONCLUSION: The results of this study suggest that use of
      periotome may be helpful in reducing post extraction discomfort.

PMID- 26225053
TI  - Superselective Intra-arterial Infusion Chemotherapy with Nedaplatin for Oral
      Cancer: A Pharmacological Study of the Dose Clearance.
AB  - INTRODUCTION: Nedaplatin (cis-diammine-glycolate platinum) is a new anticancer
      agent developed in Japan. It is especially designed to reduce adverse side
      effects of CDDP such as renal toxicity and neurotoxicity. AIM: We used nedaplatin
      as a superselective intra-arterial infusion chemotherapy for oral cancers and
      carried out a pharmacological study of the dose clearance of nedaplatin based on
      renal function as well as evaluating its efficacy, including hematological side
      effects. PATIENTS AND METHODS: Typical regimens of this chemotherapy consisted of
      5-days straight of 24-h continuous intravenous infusion of 5-Fu with a single
      shot of nedaplatin via transfemoral artery on day 4. The dose of nedaplatin was
      calculated based on the 24-h creatine clearance. A total of 37 patients who had
      oral cancer and had received 68 courses (total) of chemotherapy were found to be
      eligible for this study. RESULTS: Total and free platinum concentrations in the
      plasma were measured at each of the time points, and the area under the curve
      (AUC, measured in units of ug h/ml) was calculated based on the platinum
      concentration with the following formula: CL (clearance of free platinum: l/h) =
      0.042 * CCr (ml/min) + 5.84. The response rate was 70.1 % (in CR 51 %, in PR 19
      %). Histological CR was seen in 28.6 % of surgical specimens. Moderate
      hematological side effects were seen. However, severe adverse events were not
      observed, including those associated with cannulation of the femoral artery.
      CONCLUSION: The dose-clearance formula that was established by our study can most
      likely be utilized to accurately predict the optimal administered dose of
      nedaplatin for arterial infusion chemotherapy.

PMID- 26225054
TI  - Evaluation of Three-Dimensional Volumetric Changes After Sinus Floor Augmentation
      with Mineralized Cortical Bone Allograft.
AB  - AIM: The aim of this retrospective study was to quantify three-dimensional (3D)
      volumetric bone changes over a two-year period in maxillary sinuses augmented
      with a mineralized cortical bone allograft material (MCBA) material. PATIENTS AND
      METHODS: Eleven patients (6 males and 5 females) with mean of age of 51.6 (range:
      46-61) years were treated to increase the vertical dimension of the alveolar
      crest by maxillary sinus floor augmentation procedure. Study data were collected
      from patient records and by analyzing preoperative radiographs and cone beam
      computed tomography (CBCT) scans taken within the first two weeks after maxillary
      sinus lift (T0), immediately before implant placement four months after grafting
      (T1), and after one year of implant loading (T2). All DICOM-formatted images were
      rendered into volumetric images using software that automatically calculated the
      volume of the grafted material in cubic centimeters. RESULTS: Mean graft volume
      was 16.24 +/- 1.54 cm(3) at T0, 14.48 +/- 1.48 cm(3) at T1 and 13.06 +/- 1.39
      cm(3) at T2. Mean volume retraction resulted in 1.76 +/- 0.34 cm(3) DeltaV1 (T0
      T1) and 1.42 +/- 0.4 cm(3) DeltaV2 (T1-T2) and was 10.83 % of the initial total
      volume at (T0-T1) and 9.8 % of the total volume (T1-T2). CONCLUSION: The present
      retrospective investigation demonstrated a 20.63 % decrease in graft volume.
      Volumetric 3D assessment of CBCT scans with the selected software appeared to be
      a promising approach to quantifying long-term changes in the grafted area.

PMID- 26225055
TI  - Ramus Condyle Unit Reconstruction Using Vertical Ramus Osteotomy in
      Temporomandibular Joint Ankylosis.
AB  - INTRODUCTION: Treatment of bony Temporomandibular Joint (TMJ) Ankylosis includes
      release of the ankylosis and creation of a gap with or without insertion of
      interposing material and complete reconstruction of the joint using e.g.
      costochondral, autogenous coronoid/ankylosed mass, sternoclavicular, clavicular
      bone grafts etc. As these are non-pedicled grafts, there is eventual resorption
      with subsequent decrease in height of the ramus, facial asymmetry, deviated mouth
      opening and reankylosis. The authors have applied the method of vertical ramus
      osteotomy (VRO) on the posterior border of the mandibular ramus for
      reconstruction of the ramus condyle unit (RCU) as a pedicled graft along with
      Myofascial Temporalis Interposition for the correction of TMJ Ankylosis.
      MATERIALS AND METHODS: Ten patients of TMJ Ankylosis were included in this study.
      All ten patients were treated using VRO for the RCU reconstruction with posterior
      border of mandibular ramus after Gap Arthroplasty. Temporalis myofascial flap was
      used as an interpositional material in all patients. Patients were followed from
      20 to 30 months (mean 24 months). RESULTS: As a result of successful procedure
      the post-operative maximal mouth opening of 32-45 mm (mean 37 mm) was achieved.
      No patient experienced pain and infection at surgical site. None of the patients
      had graft rejection and reankylosis at follow-up. CONCLUSION: The results showed
      that VRO on the posterior border of the mandibular ramus seems to be an
      alternative and promising method for RCU reconstruction in patients with TMJ
      Ankylosis.

PMID- 26225056
TI  - Histological Comparison of New Biodegradable Magnesium-Based Implants for
      Maxillofacial Applications.
AB  - BACKGROUND: A variety of materials have been used for bone augmentation,
      distraction osteotomy, and in post-cancer patients following tumor removal.
      However, a temporary metal implant that would resorb after successful treatment
      is a new concept. Magnesium was suggested as a suitable material for these
      purposes because it is biocompatible, has better mechanical properties than
      titanium, and stimulates new bone formation. This study evaluates histological
      appearance of magnesium-based implants and the surrounding bone. MATERIALS AND
      METHODS: Three magnesium-based biomaterials were tested in a rabbit bone defect
      model: magnesium-hydroxyapatite (Mg-HA), W4 (96 % magnesium, 4 % yttrium), and
      pure magnesium (pure Mg). Animals were sacrificed after 6 and 12 weeks and the
      samples were analyzed histologically and histomorphometrically. RESULTS: Mg-HA
      had the highest mean amount of tartrate-resistant acid phosphatase (TRAP)
      positive cells at the implantation site of all groups. It had shown the fastest
      degradation rate already at 6 weeks but the least amount of new bone formation.
      New bone was seen forming in direct contact with pure Mg and W4. The mean gas
      volume was highest in W4 compared to pure Mg and Mg-HA but this difference was
      not statistically significant. W4 had the lowest mean number of TRAP-positive
      cells of all materials. CONCLUSION: Pure Mg and W4 were shown to be the most
      promising materials in this study in respect to the bone response to the implant
      material. They could be used for screws and plates in bone augmentation
      procedures.

PMID- 26225057
TI  - Risk of Ear-Associated Diseases After Zygomaticomaxillary Complex Fracture.
AB  - PURPOSE: Investigate the risk of ear-associated diseases after
      zygomaticomaxillary complex (ZMC) fracture in a population-based retrospective
      cohort study. MATERIALS AND METHODS: This is a retrospective cohort study using
      Taiwan's National Health Insurance Research Database of reimbursement claims. A
      total of 1,330 ZMC fracture patients and 5,320 non-ZMC fracture participants were
      included and newly developed ear-associated disease data were collected. A
      Poisson regression and multivariate Cox proportion hazard regression were used
      for data analysis. RESULTS: The ZMC fracture cohort had a higher incidence of
      tinnitus than non-ZMC fracture cohort (IRR 1.64, 95 % CI 1.37-1.96), particularly
      in younger patients (<=34 years of age; IRR 4.05, 95 % CI 3.18-5.15) and male
      patients (IRR 2.08, 95 % CI 1.12-3.73). ZMC fracture patients also showed a
      significantly increased risk of having trigeminal neuralgia [IRR 4.06, 95 % CI
      3.34-4.94, adjusted HR 4.07 (1.02-16.3)]. For sudden hearing loss and peripheral
      vertigo, the incidence densities were higher in the ZMC fracture cohort, but
      these relationships were not significant in the multivariate Cox proportional
      hazard regression analyses (HR 2.69, 95 % CI 0.76-9.53 for risk of sudden hearing
      loss; HR 1.36, 95 % CI 0.77-2.40 for risk of peripheral vertigo). CONCLUSIONS:
      The findings of the study suggest an increased risk of ear-associated diseases
      among individuals with ZMC fractures, particularly within 2-years follow-ups
      after injury. We suggest performing detailed examinations for ear-associated
      diseases in patients with ZMC fractures for early diagnosis and adequate
      treatment.

PMID- 26225058
TI  - The Effect of a Combination Saliva Substitute for the Management of Xerostomia
      and Hyposalivation.
AB  - OBJECTIVE: The objective of this study was to evaluate the difference between the
      combination agent of xylitol, beatine and olive oil in a chewable capsule versus
      the control agent of a sorbitol tablet in subjects with hyposalivation and
      xerostomia. MATERIALS AND METHODS: The subjects had xerostomia over 3 months and
      a measured hyposalivation. The study was 3 weeks in duration, with 2 treatment
      phases of 1 week and a 7 day wash out period in between. At the end of each
      treatment phase, subjects returned for a follow up evaluation. At this visit they
      were given the subjective sensation questionnaire, as well as their unstimulated
      whole salivary flow and stimulated whole salivary flow were measured. RESULTS:
      There was a greater increase in the unstimulated and stimulated whole salivary
      flow rate, although the results were not statistically significant. The
      subjective evaluation as measured by the questionnaire showed that both agents
      reduced the mean score as compared to the baseline, although only the findings in
      the active agent was statistically significant (p = 0.0015). CONCLUSION: The
      significant conclusions found in this study were that the active agent provided a
      significant subjective improvement in speech, swallowing, and decreased
      subjective xerostomia as compared to the control tablet. CLINICAL RELEVANCE: This
      combination agent has a significant effect on patients with subjective xerostomia
      but does not have a significant effect on objective hyposalivation.

PMID- 26225059
TI  - Evaluation of Crystallized Biosilicate in the Reconstruction of Calvarial
      Defects.
AB  - INTRODUCTION: The objective of this study was to assess the bone repair process
      of crystallized Biosilicate in surgically created defects on rats' calvaria. This
      biomaterial was recently developed for odontological use. MATERIALS AND METHODS:
      We used fifteen rats (rattus norvegicus albinus, Wistar), and two 5 mm surgical
      defects were performed on each of them; the defects were made with trephine drill
      on the calvarium region prior to the biomaterial placement. Groups were divided
      as follows: Group 1-defect filled with clot; Group 2-defect filled with
      crystallized Biosilicate. After 7, 14 and 28 days the animals were killed, the
      parts were retrieved and slides were prepared for histological studies. RESULTS:
      Bone formation was satisfactory in all groups, with direct contact between
      biomaterial surface and bone and absence of infection signs. The 28 days periods
      showed better results, and statistically significant difference between Clot
      Group (90.2 %) and Biosilicate (58 %; p = 0.002) was seen, regarding presence of
      bone tissue on the surgical defects. CONCLUSION: Our study revealed that defects
      filled with clot present better results on bone formation compared to
      crystallized Biosilicate, which is considered a biocompatible material with
      favorable osteoconductive properties.

PMID- 26225060
TI  - Importance of Early Cranioplasty in Reversing the "Syndrome of the Trephine/Motor
      Trephine Syndrome/Sinking Skin Flap Syndrome".
AB  - INTRODUCTION: The "Motor Trephine Syndrome (MTS)" also known as the "Sunken brain
      and Scalp Flap Syndrome" or the "Sinking Skin Flap Syndrome (SSFS)" or the
      "Syndrome of the trephined" is an unusual syndrome in which neurological
      deterioration occurs following removal of a large skull bone flap. This syndrome
      is associated with sensorimotor deficit and neurological deterioration following
      decompressive craniectomy which is performed for various neurosurgical conditions
      involving cerebral swelling causing mass effect. The neurological deterioration
      can be exacerbated or precipitated by CSF diversion procedures like a Ventriculo
      Peritoneal shunt. OBJECTIVE: It was the objective of this study to observe if any
      improvement in the patient's condition, or if any beneficial effects in his
      sensorimotor deficit could be gained by performing an early cranioplasty as
      against after the usual delay of one to two years normally allowed for post
      craniectomy cases. METHODS: A 52 year old male suffered severe head injury in a
      road traffic accident and underwent a craniectomy and contusectomy of the left
      Fronto-Temporo-Parietal (FTP) region for treatment of Acute Subdural hematoma
      (SDH) as well as hemorrhagic and non-hemorrhagic contusions of the brain with
      severe mass effect. On recovery from this acute event he was bed bound, on
      tracheostomy, his GCS was E4VTrM4 with residual right sided hemiparesis. Three
      months later, he developed Hydrocephalus for which a Right Ventriculo-Peritoneal
      (V-P) shunt was performed. Following this procedure, severe depression of the
      skin/scalp flap occurred and the neurological recovery was not as expected. He
      was diagnosed as a case of "Syndrome of the trephined". An immediate Cranioplasty
      was performed, on the third month following the craniectomy procedure, in an
      attempt to resolve the rapidly deteriorating neurological status of the patient.
      RESULTS: In the case presented, following the early Cranioplasty which was
      performed within three months of the initial craniectomy, the patient's
      neurological condition and cognitive functions showed a remarkable, immediate and
      dramatic improvement. The early Cranioplastic repair led to a remarkable clinical
      recovery of the patient, with improvement in the cognitive behavior and motor
      deficit with a rapid reversal of the sensorimotor paresis, reflecting an
      improvement in brain perfusion. CONCLUSION: Patients with the classical "Motor
      trephine syndrome/ Sinking skin flap syndrome" following large craniectomy
      defects, may hugely benefit from an early cranioplasty procedure, with a reversal
      of features of this syndrome and early recovery of their neurological and
      cognitive functions. Hence, an early cranioplasty can serve as a therapeutic
      procedure, rather than merely a cosmetic one.

PMID- 26225061
TI  - Assessment of the Efficacy of Submental Intubation in the Management of Midfacial
      and Panfacial Trauma Patients.
AB  - INTRODUCTION: Securing an airway in maxillofacial injuries remains a challenge
      and is an important objective on the part of a maxillofacial surgeon to
      thoroughly understand its management. PURPOSE: The aim of this study was to
      evaluate the efficacy and complications of submental intubation in the management
      of midfacial/panfacial trauma patients where oro-endotracheal or naso
      endotracheal intubation is contraindicated and tracheostomy can be avoided.
      PATIENTS AND METHODS: Twenty patients with maxillofacial injuries were selected
      for submental intubation who were admitted in Kamineni Hospital, Narketpally,
      Nalgonda during a 2 year period (2010-2012). The parameters used to assess the
      efficacy were; restoration of the occlusion, duration of the surgery, presence of
      scar, presence of infection, damage to vital structures or any post-operative
      salivary fistula. RESULTS: Submental intubation allowed reduction and fixation of
      all fractures without the interference of the tube during surgical procedure in
      all of the patients. There were no intra-operative complications and none of the
      patients required post-operative ventilation. There were no significant post
      operative complications. However, in one of the cases (case 4) infection of
      submental wound was seen and in another case (case 11) salivary fistula was
      formed. Both the cases were appropriately managed without any difficulty. The
      submental scar was well accepted by all the patients. CONCLUSION: Submental
      intubation is a safe and extremely useful procedure in severe maxillofacial
      injuries. It presents a low incidence of operative and post operative
      complications. It allows both the surgeon and the anaesthetist to deliver a
      better quality of patient care.

PMID- 26225062
TI  - Effect of Orthognathic Surgery on the Posterior Airway Space in Patients Affected
      by Skeletal Class III Malocclusion.
AB  - INTRODUCTION: Dentofacial deformity refers to deviations from normal facial
      proportions and dental relationships that are severe enough to be handicapping.
      These anomalies involve many aspects of patient's life and are sometimes also
      associated with a reduction of pharyngeal air space. Through orthognathic surgery
      it is possible to treat dentofacial deformities: this kind of surgery has several
      effects on skeletal structures and it has changes, as it is demonstrated by many
      studies, also on the upper airways. The orthognathic surgeries commonly used to
      correct this deformity are the mandibular setback and the maxillary advancement
      procedures. This study aims to evaluate the effects of maxillary and mandibular
      surgery on pharyngeal airway dimensions in skeletal class III malocclusions.
      MATERIALS AND METHODS: This study considers 76 patients, treated between 2007 and
      2013 by maxillary advancement (11 patients), maxillary advancement and mandibular
      setback (39 patients), maxillary advancement, mandibular setback and genioplasty
      reduction (26 patients). Cranial latero-lateral radiography was used to compare
      oropharyngeal airway morphologies before and 1 year after surgery. CONCLUSION:
      The surgeon should consider bimaxillary surgery rather than mandibular setback
      surgery to correct a class III deformity to prevent the development of
      obstructive sleep apnea syndrome; in fact, bimaxillary surgery might have less
      effect on reduction of the pharyngeal airway than mandibular setback surgery
      only.

PMID- 26225063
TI  - Pediatric Maxillofacial Trauma Outcomes Based on a Survey of 65 Patients: A
      Prospective Study of Etiology, Incidence and Methods of Treatment.
AB  - BACKGROUND: The purpose of this study was to assess the etiology, incidence, and
      various methods of treatment of maxillofacial injuries in children presenting at
      our centre and to compare our findings with literature. PATIENTS AND METHODS: We
      carried out prospective study of 65 pediatric maxillofacial trauma patients
      treated from January 2011 to October 2012 at our centre. Data was collected on
      age, gender, etiological factors, anatomic site and treatment methods. Follow-up
      was performed by recall survey. RESULTS: Out of 65 patients 17 (26.15 %)
      presented with isolated soft tissue injuries and 48 (73.84 %) patients reported
      with 81 craniomaxillofacial fractures. Falls were most common mode of injury with
      53 fractures (81.53 %). Treatment for fractures in our series comprised of
      periodic observation for non-displaced fractures (46.15 %), closed reduction
      (maxillomandibular fixation with IMF screws, acrylic cap splints) for minimally
      displaced fractures (15.38 %) and open reduction and internal fixation (ORIF) for
      grossly displaced fractures (12.30 %). CONCLUSION: Paediatric maxillofacial
      trauma can be managed conservatively and surgical treatment by ORIF is required
      in a very small group of children with grossly displaced fractures as a result of
      high velocity injuries. LEVEL OF EVIDENCE: Prognostic study, Level II.

PMID- 26225064
TI  - Kapetansky-Juri Technique to Correct the Whistlers Lip in the Multiple Operated
      Cleft Patient.
AB  - PURPOSE: One of the common sequels of a cleft lip repair may be "whistling lip
      deformity" but other deformities are also seen particularly in failed or multiple
      resurgery cases. This retrospective study was carried out to evaluate the
      usefulness of "Kapetansky-Juri" advancement flap technique to correct such
      deformities. METHODS: Ten patients of bilateral cleft lip with history of minimum
      five failed cleft lip surgeries and having residual lip deformity were operated
      using "Kapetansky-Juri" advancement flap technique and were followed up to
      minimum 36 months. RESULTS: All patients showed good tissue fullness and complete
      correction of the deformity. There was no contracture of surrounding skin or
      vermilion during follow-up period. In eight patients minimal scar formation was
      seen while two showed midline scar formation. CONCLUSION: No tissue loss due to
      vascular insufficiency was observed. The technique gives good tissue distribution
      and minimal surface scar formation.

PMID- 26225065
TI  - Bisphosphonate-Related Osteonecrosis of the Jaws and Its Array of Manifestations.
AB  - PURPOSE: Bisphosphonate (BP) therapy in the treatment of bone diseases and
      malignancy may induce a major side effect known as bisphosphonate-related
      osteonecrosis of the jaws (BRONJ). A particular view of this condition is
      reported in this case series investigating eight patients. The aim of the study
      was to evaluate the BRONJ lesions concerning their aspects and progression. Also,
      identify if it is possible to predict the degree of severity in these cases.
      METHODS: Patients were evaluated by their condition and systemic health. The
      lesions were evaluated in clinical and radiographic aspects. The patients were
      followed-up for 2 years. RESULTS: The patients presented with specific
      peculiarities, and the BRONJ lesions varied in several characteristics. The BRONJ
      lesions ranged from simple to severe conditions, and the complicated cases
      presented with major pain, swelling, secondary infection and an extensive
      necrotic area, classified with high grade of severity. CONCLUSIONS: The patients
      presented here confirm the existence of a relation between multiple features and
      BRONJ and to understand the whole process of aggravation, all systemic and local
      information have to be taken into account, together with all data related to the
      BP utilized. Regardless of the low incidence of this side effect in relation to
      osteoporosis treatment, in some cases, the BRONJ may become a severe condition
      and compromise the patient's quality of life.

PMID- 26225066
TI  - Contribution of Ultrasonography to the Diagnosis of Submucosal and Subcutaneous
      Nodular Lesions of the Oral and Maxillofacial Region: Analysis of Cases.
AB  - OBJECTIVE: The aim of this study was to evaluate the contribution of
      ultrasonography in the establishment of the diagnosis of nonspecific nodular
      lesions of the oral soft tissues. We determined the indication of use and
      reliability of ultrasonography in the field of dentistry, considering whether it
      was of value in the conclusive diagnosis of these pathologies. MATERIALS AND
      METHODS: We recruited 65 patients from the Oral Medicine Unit of Sao Lucas
      Hospital, who had submucosal and subcutaneous nodules, without established
      diagnosis. They were subjected to ultrasonography of the lesion, carried out with
      standardization of the protocol and equipment, utilizing a Doppler system. The
      ultrasonographic report was prepared by an experienced professional, noting the
      imaging characteristics as well as the possibility of diagnosis. Two calibrated
      examiners analyzed the data, comparing the ultrasonographic report with the final
      diagnosis. Accordingly, we used established scoring, where zero corresponded to
      no contribution to the final diagnosis, 1 helped in the management of the case,
      and 2 when imaging determined the diagnosis. RESULTS: A zero score was obtained
      for 12.3 % of the examinations performed, and 1 and 2 accounted for respectively
      41.5 and 46.1 %, totaling a contribution of about 88 %. Ultrasonography was of
      value in the diagnosis of vascular lesions in 93.3 % and of neoplasms in 87.5 %.
      In the salivary gland diseases, it contributed to the final diagnosis in 75 %.
      CONCLUSION: The results demonstrated that ultrasonography is an effective tool in
      the determination of the definitive diagnosis of nonspecific nodular lesions of
      the soft tissues of the oral and maxillofacial region.

PMID- 26225067
TI  - Preoperative and Postoperative CT Scan Assessment of Pterygomaxillary Junction in
      Patients Undergoing Le Fort I Osteotomy: Comparison of Pterygomaxillary
      Dysjunction Technique and Trimble Technique-A Pilot Study.
AB  - PURPOSE: To determine the rate of complications and occurrence of pterygoid plate
      fractures comparing two techniques of Le Fort I osteotomy i.e., Classic
      Pterygomaxillary Dysjunction technique and Trimble technique and to know whether
      the dimensions of pterygomaxillary junction [determined preoperatively by
      computed tomography (CT) scan] have any influence on pterygomaxillary separation
      achieved during surgery. MATERIALS AND METHODS: The study group consisted of
      eight South Indian patients with maxillary excess. A total of 16 sides were
      examined by CT. Preoperative CT was analyzed for all the patients. The thickness
      and width of the pterygomaxillary junction and the distance of the greater
      palatine canal from the pterygomaxillary junction was noted. Pterygomaxillary
      dysjunction was achieved by two techniques, the classic pterygomaxillary
      dysjunction technique (Group I) and Trimble technique (Group II). Patients were
      selected randomly and equally for both the techniques. Dysjunction was analyzed
      by postoperative CT. RESULTS: The average thickness of the pterygomaxillary
      junction on 16 sides was 4.5 +/- 1.2 mm. Untoward pterygoid plate fractures
      occurred in Group I in 3 sides out of 8. In Trimble technique (Group II), no
      pterygoid plate fractures were noted. The average width of the pterygomaxillary
      junction was 7.8 +/- 1.5 mm, distance of the greater palatine canal from
      pterygomaxillary junction was 7.4 +/- 1.6 mm and the length of fusion of
      pterygomaxillary junction was 8.0 +/- 1.9 mm. DISCUSSION: The Le Fort I osteotomy
      has become a standard procedure for correcting various dentofacial deformities.
      In an attempt to make Le Fort I osteotomy safer and avoid the problems associated
      with sectioning with an osteotome between the maxillary tuberosity and the
      pterygoid plates, Trimble suggested sectioning across the posterior aspect of the
      maxillary tuberosity itself. In our study, comparison between the classic
      pterygomaxillary dysjunction technique and the Trimble technique was made by
      using postoperative CT scan. It was found that unfavorable pterygoid plate
      fractures occurred only in dysjunction group and not in Trimble technique group.
      Preoperative CT scan assessment was done for all the patients to determine the
      dimension of the pterygomaxillary region. Preoperative CT scan proved to be
      helpful in not only determining the dimensions of the pterygomaxillary region but
      we also found out that thickness of the pterygomaxillary junction was an
      important parameter which may influence the separation at the pterygomaxillary
      region. CONCLUSION: No untoward fractures of the pterygoid plates were seen in
      Trimble technique (Group II) which makes it a safer technique than classic
      dysjunction technique. It was noted that pterygoid plate fractures occurred in
      patients in whom the thickness of the pterygomaxillary junction was <3.6 mm
      (preoperatively). Therefore, preoperative evaluation is important, on the basis
      of which we can decide upon the technique to be selected for safer and acceptable
      separation of pterygomaxillary region.

PMID- 26225068
TI  - Hybrid Implant: A Novel Implant System.
AB  - INTRODUCTION: Replacement of missing tooth has evolved from removable dentures to
      fixed dentures and recently to dental implants. The need of sufficient bone
      around the endosseous implant is critical for the success of the implant. The
      present study was aimed to evaluate the efficacy of a novel implant (HYBRID
      IMPLANT-submitted for patency) for replacement of the missing teeth. MATERIALS
      AND METHODS: 1. Research design A prospective research design with a follow up
      after 1st week ,2nd week ,3rd week,1st month ,3rd month,6th month and 1st year
      postoperatively. 2. Sampling method Population: All patients who reported for
      replacement of missing teeth. Inclusion criteria 1. All patients above the age
      group of 16years 2. Patients who need replacement of single or multiple teeth in
      the anterior or posterior region of the maxilla and mandible. Exclusion criteria
      1. Medically compromised patients. 2. Patients having craniofacial syndromes. 3.
      Sample size 5 patients were selected taking into consideration the inclusion and
      exclusion Criteria. Results PAIN All the patients were non symptomatic during the
      1st month to 1st year postoperative periods. MOBILITY: We experienced mobility
      during the 1st and 2nd postoperative periods where the implants were inserted in
      the mandibular molar region. BONE LOSS: Radiographic assessment showed no bone
      loss during the postoperative periods. CONCLUSION: The novel implant (hybrid
      implant) showed good stability and minimum patient discomfort during one year
      postoperative period evaluation. The implant system leads to new prospect in the
      field of prosthetic rehabilitation.

PMID- 26225069
TI  - Management and Treatment Outcomes of Maxillofacial Fibro-osseous Lesions: A
      Retrospective Study.
AB  - INTRODUCTION: Fibro-osseous lesions are a diverse group of bone disorders and
      include developmental, reactive or dysplastic diseases and neoplasms. They share
      overlapping clinical, radiographic and histopathologic features and demonstrate a
      wide range of biological behaviour. AIM: To evaluate the characteristics,
      treatment and outcome of benign fibro-osseous lesions of the jaws. PATIENTS AND
      METHOD: All patients with fibro-osseous lesions of the jaws treated at the
      department of Oral and Maxillofacial Surgery of the Kamineni Institute of Dental
      Sciences from 2007 to 2013 were included in this study. RESULTS: Six males and
      four females were treated. Juvenile ossifying fibroma was most often encountered
      (40 %), and the mandible was the most frequent location (70 %). Main clinical
      feature in most of the cases was a painless expansile swelling with facial
      asymmetry, and radiologically mixed (radiolucent and radiopaque lesions) were
      seen in majority of cases. All cases were surgically treated and
      histopathologically confirmed. Segmental ostectomy was performed in six cases;
      maxillectomy was done in one case and excision along with margin in three cases.
      Mean follow-up was of 3.3 years with no recurrence. CONCLUSIONS: Fibro-osseous
      lesions, although sharing similar microscopic features, exhibit a variety of
      clinical behavior rendering their treatment highly individualized. Radical
      treatment is the choice to achieve an outcome without recurrence.

PMID- 26225070
TI  - Disc Anchoring with an Orthodontic Mini-Screw for Chronic Meniscocondylar
      Dislocation of TMJ.
AB  - INTRODUCTION: Various surgical modalities have been tried for the correction of
      chronic recurrent dislocation of the temporomandibular joint. However, most of
      these techniques are aimed at creating an artificial block or removing any
      interference in the path of the translating condyle. Chronic dislocation can also
      be classified as meniscotemporal and menisocondylar, depending upon whether the
      dislocation occurs between the condyle-disc unit and temporal bone
      (meniscotemporal), or between the disc and condyle (meniscocondylar). Very few
      procedures address the primary issue of a malpositioned disc, which is the cause
      of meniscocondylar dislocation. MATERIALS AND METHODS: This study was conducted
      on 17 patients (27 joints) who reported with chronic dislocation of the
      temporomandibular joint, with MRI-proven meniscocondylar dislocation. After
      exposure of the condyle and disc through a standard pre-auricular incision, an
      orthodontic mini-screw was fixed to the posterior aspect of the condylar head and
      a 1-0 Prolene suture passed through the screw-head eyelet, plicating the
      posterior edge of the disc to the condyle. This ensured that the condyle and disc
      would move in unison. RESULTS: All the patients showed improvement in their
      symptoms of dislocation in the postoperative period, including seven patients in
      whom only a unilateral procedure was carried out. None of the patients had any
      recurrence till the 1-year followup. CONCLUSION: Our procedure addresses the
      fundamental etiology of meniscocondylar dislocation by anchoring the disc to the
      condyle by using an orthodontic mini-implant and correcting the condyle-disc
      disharmony. This technique is reliable, technically feasible, and cost-effective
      in the Indian set up.

PMID- 26225071
TI  - Importance of Clinical and Radiological Parameters in Assessment of Surgical
      Difficulty in Removal of Impacted Mandibular 3rd Molars: A New Index.
AB  - OBJECTIVE: The aim of the study is to assess the clinical and radiological
      factors that increase the surgical difficulty in removal of mandibular impacted
      3rd molar and design a new difficulty predictive index. METHODS: The data was
      collected from 100 patients with impacted mandibular 3rd molar who presented to
      Department of Oral and Maxillofacial Surgery, K.L.E's Institute of Dental
      Sciences. Clinical and radiological parameters included in the New Index were
      noted. The tooth was then removed under local anesthesia and time taken for the
      removal was noted. The Pederson Index, New Index and time taken were co-related
      using kappa statistical analysis. RESULTS: The kappa agreement between Pederson
      Index and time taken was 66.50 % (0.2231) whereas between New Index and time was
      89 % (0.7177) indicating that New Index is a better predictor of the difficulty.
      CONCLUSION: The New Index is a reliable tool in predicting the difficulty in the
      removal of mandibular impacted third molar.

PMID- 26225072
TI  - Dexmedetomidine Supported Office Based Genioplasty: A Pilot Study.
AB  - INTRODUCTION: Despite the availability of wide variety of pharmacological agents
      for dental procedural sedation, there has always been a continuous search for
      newer sedative agents. Dexmedetomidine is a newer sedative agent for provision of
      short-term sedation (<24 h) in adult patients in the intensive care unit setting.
      It is a selective alpha2 adrenergic receptor agonist. The reports on off-label
      use of this drug in a variety of settings for invasive and non invasive
      procedural sedation have provided encouraging results. MATERIAL AND METHODS: The
      present paper reports a pilot study observing clinical efficacy of the newer drug
      dexmedetomidine in patients undergoing office based sliding genioplasty for
      correction of facial asymmetry. Subjects were sedated with dexmedetomidine with a
      loading dose of 0.5 mcg/kg over 10 min followed by a continuous infusion dose of
      0.1 mcg/kg/h, the recovery process was observed for 60 min after the
      dexmedetomidine infusion was stopped. The patients were observed pre operatively,
      intra operatively (every 10 min) and postoperatively for the following parameters
      oxygen saturation (SpO2), mean arterial pressure (MAP), heart rate (HR), and
      Ramsay sedation score (RSS), respiratory rate, pain scale.

PMID- 26225073
TI  - Efficacy of Autogenous Split Thickness Calvarial Graft in the Management of
      Residual Cranial Defect.
AB  - INTRODUCTION: The patients with cranial deformity suffer from headache,
      dizziness, irritability, loss of concentration, depression, anxiety, intolerance
      to noise and vibration and neuromotor weakness. It is therefore essential to
      restore the calvarium. MATERIAL AND METHOD: This study was conducted in the
      Department of Oral and Maxillofacial Surgery, Armed Forces Medical College, Pune
      between Oct 2010 and Mar 2012. The study population was selected from the
      outpatient department and from the referred cases. The aim was to study the
      uptake of split thickness calvarial graft in the management of residual cranial
      defect. After applying the inclusion and exclusion criterions, ten cases were
      selected with residual cranial deformity, operated for cranioplasty using split
      thickness calvarial graft and evaluated. CONCLUSION: It was concluded that
      cranioplasty using autogenous split thickness calvarial graft for restoring
      cranial defects is a useful technique and this procedure allows the surgeon to
      reconstruct a moderate-to-large cranial defect, without breaching the inner
      cortical plate.

PMID- 26225074
TI  - Use of N-Butyl-2-Cyanoacrylate (Glubran2((r))) in Fractures of Orbital-Maxillo
      Zygomatic Complex.
AB  - INTRODUCTION: Fractures of the orbital-maxillo-zygomatic complex are among the
      most common fractures affecting the facial skeleton. Goal of surgical treatment
      is the realignment of fracture lines for a complete functional and aesthetic
      rehabilitation. MATERIALS AND METHODS: From January 2008 to January 2011 in the
      Department of Maxillofacial Surgery of Complesso Integrato Columbus of the
      Universita Cattolica del Sacro Cuore in Rome, 25 patients, affected by comminute
      fractures of the anterior wall of the maxillary sinus associated with fractures
      of the orbital-maxillary complex were selected. The synthesis of the larger
      fracture fragments was performed by plates and screws (1.5 mm) while a
      biocompatible glue (N-Butyl-2-Cyanoacrylate-Glubran2((r))) was applied to treat
      the comminute fractures of the anterior wall of the maxillary sinus. RESULTS AND
      CONCLUSION: The aim of our article is to report our experience and a review of
      the literature on application of-Butyl-2-Cyanoacrylate for treatment of comminute
      fractures of the anterior wall of the maxillary sinus. According to the results
      achieved in our study the N-Butyl-2-Cyanoacrylate can be indicated to treat
      comminuted fractures of the anterior wall of the maxillary sinus which could not
      easily be treated with internal rigid fixation.

PMID- 26225075
TI  - Perceptions of Pre- to Postsurgical Profile Changes in Orthognathic Surgery
      Patients and Their Correlation with Photogrammetric Changes: A Panel Study.
AB  - PURPOSE: The objective was to compare the pre- and postsurgical profile changes
      after surgical correction of prognathism and maxillary hypoplasia, as perceived
      by panels of orthodontists, maxillofacial surgeons, laypersons and patients and
      to identify photogrammetric changes that might be related to preferred ratings.
      MATERIALS AND METHODS: Each panel consisted of six males and six females who
      rated sets of pre- and postsurgical lateral photographs of 20 female and 20 male
      patients using a five-point scale. Patients rated their own set of photographs.
      Pre- to postsurgical differences of photogrammetrically assessed landmarks were
      recorded as a surgical change. RESULTS: No significant differences in ratings
      between panels and patients could be detected. Significant correlation
      coefficients (r) were obtained between the ratings of all panel groups and
      between the ratings and changes in facial convexity (r = 0.351-0.542).
      Correlations with changes of the mentolabial angle were found to be significant
      for old orthodontists, male laypersons, and male patients (r = 0.332-0.609).
      Ratings of female and young laypersons were correlated with the horizontal
      changes in the lower face (r = 0.324-0.379). CONCLUSION: Information gathered
      from this study will support the cooperation of the medical staff and might
      assist in treatment planning.

PMID- 26225076
TI  - Comparitive Evaluation of Propofol and Midazolam as Conscious Sedatives in Minor
      Oral Surgery.
AB  - OBJECTIVE: The objective of the study was to assess the efficacy of propofol and
      midazolam as an intravenous sedative agent in minor oral surgical procedures in
      terms of: (a) the onset of action, (b) heart rate, (c) oxygen saturation, (d)
      systolic and diastolic blood pressure, (e) respiratory rate, (f) pain during the
      injection of sedative agent, (g) recovery period, (h) side effects, (i) patient's
      cooperation during the surgery. METHODOLOGY: This was a double blind randomized
      study in which one group of 20 patients received propofol with the induction dose
      of 0.5 mg/kg and 50 MUg/kg/min which was administered by syringe infusion pump as
      a maintenance dose and the other group received midazolam in a single dose of 75
      MUg/kg and no maintenance dose was given, instead 5 % dextrose was administered
      by syringe infusion pump at the rate of 50 MUg/kg/min. Since propofol was milky
      white in colour, a green cloth was covered over the infusion pump in all cases.
      The surgeon, assistants and observers were blind about the medications which
      would be given to the patient for sedation. After the administration of the
      sedative, local anesthesia was achieved with 2 % lignocaine hydrochloride.
      RESULTS: The onset of action in propofol group was significant as onset of action
      was faster. The maximum increase in heart rate in propofol group was at 10 min
      intraoperatively (Mean +/- 80.40 +/- 12.73) and that in midazolam group was at 15
      min intraoperatively (Mean 79.25 +/- 13.44). Post operatively the heart rate
      decreased near to the baseline value in both the groups. The average oxygen
      saturation before induction in propofol group was 99.7 +/- 0.73 % and that of
      midazolam group was 99.15 +/- 01.31 P = 0.314. None of the patients in this study
      developed apnea. The systolic blood pressure (Mean +/- SD) before induction in
      both the groups decreased from the baseline value after the administration of
      sedatives. The diastolic blood pressure (Mean +/- SD) before induction in both
      the groups decreased from the baseline value after the administration of
      sedatives and the decreased diastolic blood pressure was maintained throughout
      the procedure. The respiratory rate (Mean +/- SD) before induction in both the
      groups decreased from the baseline value after the administration of sedatives.
      The decreased respiratory rate remained throughout the surgical procedure. Pain
      during the injection of the sedatives was reported by nine patients (45 %) in the
      propofol group whereas none of the patients in midazolam group complained of pain
      during the injection. This is statistically significant (P = 0.001). The recovery
      time (Mean +/- SD) in propofol group was 22.50 +/- 3.04 (range 15-25 min) and
      that in midazolam group was 33.75 +/- 3.93 (range 30-40 min), which was
      statistically significant (P < 0.001). Patients in the propofol group were
      significantly less co-operative than midazolam group at both 10 and 25 min intra
      operatively. CONCLUSION: The design of the present study permitted qualitative
      assessment of propofol and midazolam as sedative agents in minor oral surgical
      procedures. The ideal anesthetic agent should provide rapid onset of action,
      profound intra operative amnesia while ensuring rapid recovery without much
      complications. There were no significant differences in either patient
      demographics or surgical characteristics between the two groups. The propofol
      group was less co-operative than midazolam group. Pain during the injection of
      sedative was a significant adverse effect in the propofol group. Cardiovascular
      parameters remained stable throughout the procedure in both study groups and no
      intervention was required. However recovery and onset of action was faster in the
      propofol group as compared with the midazolam group.

PMID- 26225077
TI  - Role of Rapid Tetanus Antibody Test in Accident and Emergency Department.
AB  - INTRODUCTION: Tetanus remains a problem of immense concern worldwide. Management
      of tetanus with its attendant complications are challenges to the physician and
      its prevention is the chief priority. The choice of tetanus prophylaxis for
      patients with wounds depends on obtaining their vaccination history, which has
      been demonstrated to be unreliable. The tetanus antibody test may avoid
      inadequate prophylactic measures and reduce costs. PURPOSE: This study is
      conducted to determine the feasibility of rapid tetanus antibody test (SD
      Bioline) in the accident and emergency department. METHODS: A randomized
      prospective study was conducted on 50 patients, divided into two groups-A and B
      with 25 patients each respectively. Group A had patients with a history of
      tetanus immunization <5 years elapsed from the last booster dose. Group B had
      patients who did not know the immunization status or more than 5 years elapsed
      from the last booster dose of tetanus immunization. Groups A and B were further
      classified into Group 1 and Group 2 based on whether the wound is tetanus prone
      or a clean wound respectively. Tetanus antibody test was done using whole-blood
      from the patients by finger prick. RESULTS: Among the 50 patients, 25 (50 %) were
      classified as 'unprotected' according to the history. Thirteen of the 25 patients
      showed tetanus antibody positive. In Group A, only 9 of the 25 patients showed
      tetanus antibody positive. CONCLUSION: The rapid tetanus antibody test in the
      emergency room could make tetanus prevention more accurate with improved
      technical feasibility. The test may eliminate unnecessary injecting of vaccine,
      reduce the cost and can be performed at the hospital setting.

PMID- 26225078
TI  - Post-operative Stability After Bimaxillary Surgery in Patients with Facial
      Asymmetry: Comparison of Differences Among Different Original Skeletal Class
      Patterns.
AB  - PURPOSE: When improving jaw deformity by two-jaw surgery, we are of the opinion
      from our clinical experience that a certain degree of undercorrection is
      occasionally beneficial from the perspective of stability. Functional
      deterioration is not always seen with undercorrection. We conducted this
      retrospective study to assess post-operative stability in patients with facial
      asymmetry, with the aim of both clarifying differences between the original three
      skeletal class patterns, and confirming the efficacy of surgery performed on the
      basis of our concept. PATIENTS AND METHODS: All patients received optimal
      orthognathic treatment before and after surgery. Surgery was performed by our
      concept that undercorrection is not always bad. Nineteen patients were enrolled,
      and separated into three skeletal classes according to the ANB angle, because of
      the difference of the treatment modalities between them. Evaluations were
      performed by cephalometric measurements taken at least two-year post-operatively.
      Transverse occlusal cant, chin deviation, point A, point B, overjet and overbite
      were assessed. RESULTS: In all patients, transverse occlusal cant improved to <4
      degrees , which has been reported as the threshold for visual recognition of
      facial symmetry. Chin deviation was also improved to the degree at which soft
      tissue can sufficiently mask the asymmetry. The changes remained stable
      throughout follow-up and satisfaction was obtained from all patients.
      CONCLUSIONS: Irrespective of original skeletal class patterns, post-operative
      stability of patients with facial asymmetry was achieved. Undercorrection is thus
      by no means problematic from the clinical perspective of stability and our
      concept of approach appears valid.

PMID- 26225079
TI  - Study of Efficacy and the Comparison Between 2.0 mm Locking Plating System and
      2.0 mm Standard Plating System in Mandibular Fractures.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy and comparison
      between 2.0 mm locking plate system and 2.0 mm Champy's titanium mini plating
      system in mandible fractures. MATERIALS AND METHODS: A total of 20 patients with
      mandibular fractures were selected and divided into two groups A and B on
      randomized basis. Group A was treated with open reduction internal fixation using
      2.0 mm locking plates and group B with 2.0 mm Champy's titanium miniplates. All
      patients were followed up for 12 weeks postoperatively. RESULTS: Results of the
      study show less screw loosening, less precision in plate adaptation and less
      alteration of the osseous or occlusal relationship upon screw tightening in group
      A. Chi square test was applied to compare the results between the two groups.
      Statistical analysis did not show significant difference of incidence of
      malocclusion between the two groups (p value = 0.606). Statistical analysis using
      un-paired t test showed significant difference of working time between the two
      groups (p value = 0.00296). When comparing the overall complication rates
      according to plates used, the chi(2) test showed no statistically significant
      difference between the locking and nonlocking plates (p > 0.05). CONCLUSION: It
      is observed in our study that the locking plate/screw system offers significant
      advantages over the conventional plating system. The precise adaptation required
      for using conventional plates is not needed when this locking plate/screw system
      is used. Locking plate/screw system provides better stability than the
      conventional plate/screw system.

PMID- 26225080
TI  - Mandibular Third Molar Extraction Wound Healing With and Without Platelet Rich
      Plasma: A Comparative Prospective Study.
AB  - AIMS: To evaluate the efficacy of autologous platelet rich plasma (PRP) in
      regeneration of bone and to assess clinical compatibility of the material in
      mandibular third molar extraction socket. OBJECTIVE OF THE STUDY: To compare the
      healing of mandibular third molar extraction wounds with and without PRP.
      MATERIALS AND METHODS: Group A consists of the 30 patients where PRP will be
      placed in the extraction socket before closure of the socket. Group B consists of
      30 patients who will be the control group where the extraction sockets will be
      closed without any intra socket medicaments. The patients would be allocated to
      the groups randomly. RESULTS: Soft tissue healing was better in study site
      compared to control site. The result of the study shows rapid bone regeneration
      in the extraction socket treated with PRP when compared with the socket without
      PRP. Evaluation for bone blending and trabecular bone formation started earlier
      in PRP site compared to control, non PRP site. Also there was less postoperative
      discomfort on the PRP treated side. CONCLUSION: Autologous PRP is biocompatible
      and has significant improved soft tissue healing, bone regeneration and increase
      in bone density in extraction sockets.

PMID- 26225081
TI  - Autotransplantation of Teeth Associated with Dentigerous Cyst: A Case Report.
AB  - This paper discusses the treatment of impacted permanent incisors and unerupted
      ectopic canine associated with a dentigerous cyst in mixed dentition that was
      successfully managed by the combined approach of decompression followed by
      enucleation, primary closure, autotransplantation and endodontic therapy which
      enabled the utilization of teeth which were hitherto nonfunctional, transferred
      to an optimal functional and esthetic position. Decompression is a less invasive
      technique which reduces the cystic pressure, avoids a more stressful surgical
      procedure and necessity for general anesthesia. It gives more pleasing results as
      the body's own mechanism heals the defect gradually. Autotransplantation of teeth
      induces bone formation around the root with the help of viable periodontal
      ligament on their root surface. In this case, bone lost by cyst was regenerated
      and lamina dura was appreciable in the follow up radiographs and transplanted
      teeth are functioning well. 

PMID- 26225082
TI  - Recurrent Ameloblastoma in the Free Fibula Flap: Review of Literature and an
      Unusual Case Report.
AB  - Ameloblastoma is the second most common odontogenic tumor of the oral cavity with
      the primary site being the mandible. The ratio of maxillomandibular involvement
      however is 5:1 in favor of the mandible. The most common complaint is a painless
      swelling over the mandibular area. Despite its benign nature, ameloblastoma has a
      high local recurrence rate, with the most recurrences seen within 5 years after
      operation. Biopsy and radiological evaluation may be helpful in differentiating
      the subtypes of ameloblastoma. Differentiation is important because some subtypes
      are more aggressive than the others. Preoperative planning may be done according
      to this classification, which can help decrease the recurrence rate. In our case,
      a 26-year-old female patient with recurrent ameloblastoma which developed on the
      fibular flap is presented. The free fibular flap and the left parasymphyseal part
      of the mandible were totally excised. Ameloblastoma was confirmed on pathological
      examination. We reconstructed the left mandibular site with a reconstruction
      plate and recurrence was not seen during follow up period. 

PMID- 26225083
TI  - Bilateral Calcifying Odontogenic Cyst: A Rare Entity.
AB  - The calcifying odontogenic cyst (COC) accounts for 1 % of jaw cysts, found most
      commonly as central lesion. The COC usually manifests itself as a painless, slow
      growing swelling, anterior to the first molar region. Radiographically it appears
      as a well-defined, unilocular radiolucency, and may have a radiopaque mass in its
      center. Majority of the cases appear before the fourth decade of life. The COC is
      found rarely in patients in the first decade of life. Histopathological features
      include a cystic lining demonstrating characteristic "Ghost" epithelial cells
      with a propensity to calcify. Here we report the unusual occurrence of a case of
      8 year child diagnosed with bilateral COC on right and left side of mandible. 

PMID- 26225084
TI  - Foreign Body in the Orbital Floor: A Case Report.
AB  - An 11 year old girl reported to the department with the complaint of redness and
      pus discharge from her left eye. History revealed that the patient had a fall
      from bicycle and injured her left eye one month earlier. CT scan reported an ill
      defined radiolucency present in the floor of the orbit. On surgical exploration
      we retrieved a wooden piece along with its disintegrated particles from the
      orbital floor. The need for clinical suspicion, proper history, diagnostic
      modalities and management of intra orbital foreign bodies are discussed in this
      article. 

PMID- 26225085
TI  - Giant Osteoma of Mandible Causing Dyspnea: A Rare Case Presentation and Review of
      the Literature.
AB  - Osteomas are benign slow growing tumors of bone. Tumors are usually asymptomatic
      until they attain remarkable size and cause asymmetry or dysfunction. In view of
      few reported cases of giant osteoma of mandible, this article presents a case of
      giant osteoma of left mandible in a 53-year old male causing dyspnea due to
      compression of air way space. 

PMID- 26225086
TI  - An Unusual Presentation of Stafne Bone Cyst.
AB  - Stafne bone cyst is a rare mandibular defect. It is a developmental abnormality
      that commonly presents as a small, well demarcated, and asymptomatic radiolucency
      seen at the angle of the mandible below the mandibular canal. There are usually
      no clinical signs nor symptoms. Diagnosis is commonly by plain X-ray, but use of
      more accurate imaging such as MRI is required in atypical cases. This case study
      reports an unusual presentation of Stafne bone cyst in the ramus of the mandible
      in a young man and reviews the relevant literature. 

PMID- 26225087
TI  - Calibre Persistent Labial Artery: Clinical Features and Immunohistochemistry
      Diagnosis.
AB  - Calibre persistent labial artery (CPLA) usually presents as an asymptomatic
      papule on the lower lip and can be easily misdiagnosed as a mucocele,
      haemangioma, venous lake, varix or fibroma. When it is ulcerated, squamous cell
      carcinoma is the most usual differential diagnosis. Here, we report a case of a
      25-year-old woman with no previous relevant medical history who presented with a
      complaint of an asymptomatic, non-ulcerated, progressively growing nodule (over
      the last 5 months) on the upper lip. In this case, the diagnosis was made
      clinically and confirmed by immunohistochemical analysis. We conclude that
      clinicians should be aware of CPLA and it should be included in the differential
      diagnosis of labial mucosal papules. Sometimes, the immunohistochemical analysis
      is necessary to make a correct diagnosis. 

PMID- 26225088
TI  - Restoration of Atrophic Edentulous Maxilla of a Patient with Ectodermal Dysplasia
      Using Quadruple Zygomatic Implants: A Case Report.
AB  - Rehabilitation of patients with ectodermal dysplasia often presents clinical
      challenge due to hypodontia, anodontia, and severe atrophy of edentulous ridges.
      Zygomatic implant therapy can be used as a method of achieving osseointegration
      without bone grafting in such situations. This clinical report describes the
      dental rehabilitation of atrophic maxilla of a 26-year old female patient with a
      fixed prosthesis, immediately loaded on four zygomatic implants. 

PMID- 26225089
TI  - Oral Cysticercosis: A Case Report and Review of Literature.

PMID- 26225090
TI  - Karapandzic Flap in Reconstruction of Post-traumatic Lower Lip Defects: Report of
      Two Cases.
AB  - Reconstruction of lower lip is a challenge to the surgeon who seeks excellence in
      restoration of both aesthetics and functions. The defects may arise either due to
      trauma, developmental anomaly or post-excision of malignant conditions. The
      reconstruction of rectangular shaped full thickness defects of lip may be
      achieved with bilateral advancements of the remaining lip segments. We report two
      cases with post-traumatic full thickness avulsion of central two third of lower
      lip, reconstructed with Karapandzic flap. 

PMID- 26225091
TI  - Ophthalmic Complication Following Posterior Superior Alveolar Nerve Block for
      Tooth Extraction! A Rare Occurrence.
AB  - One of the most commonly asked question by a patient who comes for extraction
      especially in the rural areas is whether the procedure will cause problems to the
      eye!! In reality however, ophthalmic complications following routine maxillary
      molar extractions are practically unheard of. When they occur they can be
      extremely unnerving not just to the patient but also to the surgeon. Patients
      generally panic which makes it tougher for the clinician to assess the situation.
      We present a case of a 26 year old female patient developing ophthalmic
      complication following local anesthesia administration during extraction of upper
      left maxillary third molar. In this article, ophthalmic complications arising
      from posterior superior alveolar nerve block are discussed and management
      guidelines are highlighted. 

PMID- 26225092
TI  - A Simple Technique for Removal of Broken Root Tip of Maxillary Premolars: A
      Technical Note.
AB  - INTRODUCTION: Therapeutic extraction of maxillary premolars is often indicated
      for orthodontic treatment. Extraction as well as retrieval of broken root tips in
      cases should be minimally invasive aiming to preserve the alveolus as well as the
      buccal and palatal cortical plates. MATERIALS AND METHODS: Here a technique is
      described that we have been employing for retrieving broken maxillary premolar
      root tips which have the bevel towards the buccal cortex. CONCLUSION: The method
      is simple, atraumatic and effective.

PMID- 26225093
TI  - Tunnel Technique for the Closure of an Oroantral Fistula with a Pedicled Palatal
      Mucoperiosteal Flap.
AB  - BACKGROUND: Oroantral fistula may develop as a complication of tooth extraction
      owing to infection, trauma, or removal of maxillary cyst or tumors. Closure by
      using a palatal mucoperiosteal flap with the greater palatine vessels is a very
      traditional and basic technique. The palatal mucosa is thick and is firm.
      However, deformation can occur with shifting of the mucoperiosteal flap, survival
      of the flap may be unsuccessful, and patients may have substantial intraoral
      discomfort felt until healing of the eminence with the arcuation. As a method to
      relieve these problems, we present a mucoperiosteal tunnel technique for the
      closure of oroantral fistula by using a palatal mucoperiosteal flap pedicled with
      the greater palatine vessels. METHOD: A 42-year-old man and a 69-year-old woman
      each had a palatal fistula after palatal tumor resection and tooth extraction,
      respectively. We designed a mucoperiosteal flap pedicled with the left greater
      palatine vessel. We ablated the mucoperiosteum between the fistula and the
      mucoperiosteal flap, and passed this flap under the ablated mucoperiosteum as a
      tunnel. RESULT: One year after surgery, the fistula had not reappeared and the
      mucoperiosteal flap harvest did not generate dyskinesis of the soft palate.
      CONCLUSION: Tunnel technique for the closure of an oroantral fistula with a
      pedicled palatal mucoperiosteal flap is obtains good fructification.

PMID- 26225094
TI  - "Bat Wing Surgical Approach for the Temporomandibular Joint".
AB  - INTRODUCTION: The temporomandibular joint (TMJ) is anatomically complex; with its
      close proximity to neurovascular structures, including the facial nerve that
      gives a high degree of difficulty during surgical exposure. When the first
      description on TMJ surgery by Orlow in 1913 was published it gave an account
      describing the basic retroauricular, preauricular, endoaural and submandibular
      approaches, on treatment of articular pathologies as used today. The proposed
      study of the 'Bat Wing' approach, first described in 1993 by Garcia y Sanchez
      J.M. as a surgical alternative, offers great advantages is that it avoids the
      section of the ear canal and provides a wide surgical field. The management of
      the proposed technique has wide application with multiple joints addressed,
      achieving major objectives such as avoiding facial nerve damage, as well as
      avoiding the section of the external auditory canal with an optimum visibility of
      the operative field. MATERIAL AND METHODS: The Department of Maxillofacial
      Surgery National Medical Center XXI Century records over a period of
      approximately 18 months have completed twenty TMJ surgeries using the 'Bat Wing',
      approach. CONCLUSIONS: The bat wing approach is a surgical alternative that
      offers broad exposure of the surgical field in TMJ, it is effective and meets the
      goal of exposing the area to intervene safely, good visibility and access to the
      site to intervene. It perfectly fulfills the above described.

PMID- 26225095
TI  - Effectiveness of Hexetidine 0.1% in Eliminating Candida albicans Colonizing
      Dentures: A Randomized Clinical In Vivo Study.
AB  - BACKGROUND: Effective cleaning of dentures is important to maintain a good oral
      hygiene for patients suffering from denture stomatitis (DS). This study aimed to
      evaluate the efficacy of hexetidine 0.1% in eliminating C. albicans colonizing
      dentures. MATERIALS AND METHODS: A total of 40 denture wearers (18 men, 22 women;
      age range 40-80 years) with clinical evidence of DS were randomly divided into 2
      groups, 1 test, and 1 control. The dentures of the test group were treated by
      immersion in hexetidine 0.1% while those of the control group were immersed in
      distilled water. Swab samples from the palatal surfaces of the upper dentures
      were collected before and after of cleaner use and examined mycologically.
      RESULTS: Reduction in the number of colony-forming units (CFU) of C. albicans
      after immersion of the dentures with hexetidine 0.1% was evaluated compared to
      those of the control group. CONCLUSION: Hexetidine 0.1% solution tested for the
      first time as a product of disinfection of the acrylic dentures showed average
      results after immersion of 8 night hours for 4 days.

PMID- 26225096
TI  - Clinical and Radiographic Evaluation of Median Lingualized Occlusion in Implant
      Retained Mandibular Complete Overdenture.
AB  - BACKGROUND: The purpose of this study was to evaluate clinically and
      radiographically median lingualized occlusion in implant-retained mandibular
      complete overdenture. MATERIALS AND METHODS: Ten completely edentulous male
      patients were participated in this study. Each patient received two implants in
      the intraforaminal area of the edentulous mandible that were left unloaded for 4
      months. Patients were received conventional maxillary complete denture and
      implant mandibular overdenture with ball and socket attachment. The posterior
      teeth were set according to median lingualized occlusion scheme. All patients
      were evaluated clinically and radiographically immediately after denture
      insertion, 6 and 12 months of overdenture insertion. RESULTS: The results
      revealed significant differences in probing depth, gingival index, plaque index,
      and marginal bone height between the different follow-up periods. With the
      limitation of this study, and according to the results of the mean marginal bone
      loss and the other peri-implant parameters after 1 year of loading. CONCLUSION:
      The implant retained overdenture with the median lingualized occlusal scheme may
      be recognized as being acceptable according to the general implant success rates
      and criteria.

PMID- 26225097
TI  - In Vitro Solubility and Wear Rates of Silorane and Dimethacrylate Resin Based
      Composite Restorative Materials under Different pH Conditions.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of different pH
      solutions on the solubility and wear resistance of Silorane and dimethacrylate
      resin based composite restorative materials. MATERIALS AND METHODS: Two different
      resin based restorative materials (Filtek Silorane P90 and hybrid composite Z100)
      were tested. Different pH solutions (2.5 and 5) also were used. A total of 60
      samples of each type of selected composite were prepared. Specimens were immersed
      in each type of pH solutions (2.5 and 5) and distilled water as a control group
      for 24 h then the specimens was subjected to the required mechanical tests.
      RESULTS: Significant statistical differences were observed regarding water
      solubility and wear values in different pH solutions. Filtek Silorane presented
      the smallest values of water solubility and wear values. CONCLUSION: Under tested
      experimental conditions, the pH solutions used in this study showed pronounced
      effect on water solubility and wear values of both two restorative materials.
      Finally, within the limitation of this study we recommended to use Filtek
      Silorane (P90) instead of hybrid (Z100) due to its low solubility values under
      different pH solutions.

PMID- 26225098
TI  - Frequency of Iatrogenic Errors through Root Canal Treatment Procedure in 1335
      Charts of Dental Patients.
AB  - BACKGROUND: Endodontic procedures such as root canal treatment would be at the
      risk of failure like other medical interventions due to any unsuitable
      conditions. This has a causative effect in making the procedure more complicated
      to resulting in weak prognosis finally. Technical errors such as ledge,
      perforation, obstruction, broken instrument, etc. make infection control too hard
      or impossible. The aims of this study are common errors frequency and types of
      root canal treatments focusing on defined groups of dental students in Qazvin,
      Iran. MATERIALS AND METHODS: All the errors were divided into three major kinds
      of: (1) During providing access cavity, (2) cleaning and preparation and (3)
      canal obturation. RESULTS: A total number of 1335 charts of the cases were
      studied in the field of root canal treatment. The whole number of charts, which
      reported errors was 880 (66%) while 455 (34%) error-free ones. The most frequent
      error in upper incisors was void with the rate of 50.9%, followed by overfilling
      (apical perforation) in 18.2%. The same errors were also most common for lower
      incisors in addition to imperfect cleaning. CONCLUSIONS: The current study
      identified the least mistakes through the process of providing access cavity and
      instrumentation phase comparing obturation phase, which had the most frequent
      errors including void, overfilling and imperfect cleaning.

PMID- 26225099
TI  - Effect of Emergency Primary Care Training Workshops: A Survey on 45 Iranian
      Dental School Interns.
AB  - BACKGROUND: Dentistry is a therapeutic health care profession that is related to
      people's health. Moreover medical emergencies often occur in dental offices that
      little awareness of the professional workers can have unpleasant consequences.
      MATERIALS AND METHODS: In this interventional study, a survey of 45 final year
      dental students was examined. To do so, a test in terms of knowledge was taken as
      a standard questionnaire, and in the practical part a test was taken as on
      objective structured clinical examinations (OSCE) test in three stations, before
      and after the workshop; identification of emergency instruments, the performance
      of intramuscular and intravenous injections and cardiopulmonary resuscitations
      before and after the workshop obtained data were analyzed using, SPSS version 16,
      Student's t-test and paired T. RESULTS: Using the t-test, mean score of the
      students' knowledge prior to and after the workshop were 51 +/- 13.08 and 83.41
      +/- 8.65 respectively (P = 0.000). The practical score (OSCE) of dental students
      was 50.85 +/- 13.09, which after the workshop came up to 85.73 +/- 7.06 came up
      (P = 0.000). T-test of the performance before and after the workshop had a
      significant difference in each of the three stations. Significant differences
      between male and female students' knowledge and performance scores don't exist
      before and after the workshop (P > 0.05). CONCLUSION: The level of knowledge and
      performance of students were assessed as average, therefore, training courses and
      revised the curriculum units are required.

PMID- 26225100
TI  - Difficulties Encountered during Transition from Preclinical to Clinical
      Endodontics among Salman bin Abdul Aziz University Dental Students.
AB  - BACKGROUND: The quality of academic training can best be analyzed by including
      the student's perceptions. The aim of this study is to evaluate the short comings
      in preclinical endodontic training and also to find out key areas to stress upon
      for better student understanding and treatment outcome. MATERIALS AND METHODS: A
      total of 72 structured questionnaires were distributed to the dental students who
      have already entered or finished clinical endodontic training in 4(th) year after
      successfully completing the preclinical endodontic course in 3(rd) year. The
      questions were focused on the list of difficulties encountered during each step
      of endodontics including patient consideration, access related difficulties,
      difficulties during working length determination, cleaning and shaping and
      obturation. The difficulty level for each of the questions was also rated on a
      scale of 1-3. About 88% of the questionnaires were returned for evaluation. The
      obtained answers were analyzed generating a data showing the type and level of
      difficulty. RESULTS: Locating the apical constriction and controlling the length
      of the master cone has the highest percentage of difficulty among all the groups.
      CONCLUSIONS: This study helped in highlighting key areas of difficulties faced by
      the students. The training for students in future needs to be amended so that
      they are better able to manage such difficulties.

PMID- 26225101
TI  - Shear Bond Strength of Superficial, Intermediate and Deep Dentin In Vitro with
      Recent Generation Self-etching Primers and Single Nano Composite Resin.
AB  - BACKGROUND: This in vitro study is intended to compare the shear bond strength of
      recent self-etching primers to superficial, intermediate, and deep dentin levels.
      MATERIALS AND METHODS: All teeth were sectioned at various levels and grouped
      randomly into two experimental groups and two control groups having three
      subgroups. The experimental groups consisted of two different dentin bonding
      system. The positive control group consisted of All Bond 2 and the negative
      control group was without the bonding agent. Finally, the specimens were
      subjected to shear bond strength study under Instron machine. The maximum shear
      bond strengths were noted at the time of fracture. The results were statistically
      analyzed. RESULTS: Comparing the shear bond strength values, All Bond 2 (Group
      III) demonstrated fairly higher bond strength values at different levels of
      dentin. Generally comparing All Bond 2 with the other two experimental groups
      revealed highly significant statistical results. CONCLUSION: In the present
      investigation with the fourth generation, higher mean shear bond strength values
      were recorded compared with the self-etching primers. When intermediate dentin
      shear bond strength was compared with deep dentin shear bond strength
      statistically significant results were found with Clearfil Liner Bond 2V, All
      Bond 2 and the negative control. There was a statistically significant difference
      in shear bond strength values both with self-etching primers and control groups
      (fourth generation bonding system and without bonding system) at superficial,
      intermediate, and deep dentin. There was a significant fall in bond strength
      values as one reaches deeper levels of dentin from superficial to intermediate to
      deep.

PMID- 26225102
TI  - Fracture Resistance of Teeth Restored with Various Post Designs and Cemented with
      Different Cements: An In-vitro Study.
AB  - BACKGROUND: Studies have been carried out on endodontically treated teeth
      restored with and without ferrule, and influence of the cementing medium, to
      evaluate their effect on fracture resistance. This study was conducted on 28
      freshly extracted maxillary central incisors. Specimens were restored with two
      types of post designs, and cemented with two different luting agents, and tested
      for fracture resistance. MATERIALS AND METHODS: A total of 28 freshly extracted
      maxillary central incisors were used. Specimens were restored with two types of
      post designs and cemented with two different luting agents and tested using
      Instron universal testing machine. The statistical analysis was performed using
      the Kruskal-Wallis test (H) and Tukey honest significant test. RESULTS: Ferrule
      helped in increasing the fracture resistance of endodontically treated teeth.
      Resin cement showed better results than zinc phosphate cement. The combination of
      the post with ferrule and resin cement showed the greatest resistance. The
      combination of the post without ferrule and zinc phosphate cement showed the
      least resistance. Resin cement increased the resistance of even without ferrule.
      CONCLUSION: There was a positive effect of a ferrule in increasing the fracture
      resistance. Resin cement showed better resistance than zinc phosphate cement.

PMID- 26225103
TI  - Comparison of Cone Beam Computed Tomography, Orthopantomography with Direct Ridge
      Mapping for Pre-Surgical Planning to Place Implants in Cadaveric Mandibles: An Ex
      Vivo Study.
AB  - BACKGROUND: Implant treatment is today a common and most widely accepted
      prosthetic therapy worldwide. The quality and quantity of the bone available at
      the anticipated implant site is of prime importance. Accurate measurement of
      alveolar bone and adjacent anatomic structures are of paramount importance in
      implant insertion. Proper pre-surgical assessment requires precise radiographic
      visualization of anatomic structures and pathologic conditions. However, the
      concern for radiation exposure has also grown. MATERIALS AND METHODS: A total of
      15 partially or completely edentulous human cadaveric mandibles were used which
      were further subdivided into three further groups for cone-beam computed
      tomography (CBCT), orthopantomography (OPG), and direct measurements (DM).
      Mandibles were prepared for each sample and subjected to radiographs according to
      the respective techniques, and radiographic measurements were done using the
      appropriate software. The cadaveric mandibles were then sectioned, and the actual
      measurements were done using a digital vernier caliper. RESULTS: Analysis of
      variance test revealed that there was no significant difference among the three
      different measurements techniques. CONCLUSION: A sizable portion of the CBCT
      measurements with respect to width showed slight overestimation when compared to
      DMs. There were no statistically significant differences found between CBCT, OPG,
      and DM when height was taken into consideration.

PMID- 26225104
TI  - Comparative Evaluation of Bond Strength of Dual-Cured Resin Cements: An In-Vitro
      Study.
AB  - BACKGROUND: To compare the microtensile bond strength of resin cements to enamel
      and dentin and to determine the type of bond failure using stereomicroscope.
      MATERIALS AND METHODS: In this in-vitro study 40 teeth were embedded in acrylic
      resin and divided into two main groups i.e., Group A for enamel and Group B for
      dentin. Each group is again subdivided into four subgroups, which are as follows;
      Subgroup 1 for Calibra resin cement, Subgroup 2 for Paracem, Subgroup 3 for
      Variolink II and Subgroup 4 for Rely X ARC. These resin cements were applied on
      enamel and dentin according to manufacturer's instructions followed by
      incremental build-up of composite resin on the top of resin cements. Each tooth
      was sectioned perpendicular to the resin-substrate interface with a slow speed
      diamond saw under water cooling yielding sections of approximately 1 mm(2). On an
      average, three sections from each tooth were used for testing. The beams obtained
      after sectioning were stressed to failure under tension in a custom made
      stainless steel forceps held in a universal testing machine (Lloyd) at a
      crosshead speed of 1.0 mm/min. Results were analyzed using two-way analysis of
      variance, independent t-test, and Tukey's HSD post-hoc test. RESULTS: Cements
      bonded to enamel substrates showed higher mean bond strength compared to dentin,
      which is statistically significant. Rely X ARC showed highest mean bond strength
      to both the substrates. CONCLUSION: There was a significant difference between
      the bond strength to enamel and dentin and, Rely X ARC resin cement showed higher
      bond strength compared with the other groups.

PMID- 26225105
TI  - Incidence of Tooth Size Discrepancy in Different Groups of Malocclusion and its
      Relation to Extraction.
AB  - BACKGROUND: For proper intercuspation, the teeth must be proportional in size. If
      teeth are mismatched, with unusually large teeth in one arch compared to the
      other, then an ideal occlusion cannot be attained. This study has been done to
      determine the prevalence of tooth size discrepancies among orthodontic patients
      in general and also between different malocclusion groups, sex, and to analyze
      the change in the degree of severity in Bolton discrepancy before and after the
      hypothetical premolar extraction. METHODS: The study was carried out on randomly
      collected 100 pre-treatment dental casts. Tooth size analyses were performed on
      these pre-treatment models and Mesio distal tooth size ratios were measured as
      described by Bolton before and after various patterns of hypothetical extraction.
      RESULT: The results were statistically evaluated using ANOVA and paired samples t
      test. 5 out of 100 patients are seen with severe Bolton discrepancy with Bolton
      values (BV) ranging above and below 2 standard deviation. Statistically
      insignificant difference is seen between males and females and also between
      various groups of malocclusion. The difference between the pre-treatment and post
      extraction BV was found statistically significant for the first premolar
      extraction and insignificant for others. CONCLUSION: The results of this study
      indicate a new point of view to the question of which teeth to extract when
      evaluated for tooth size aspect only.

PMID- 26225106
TI  - Evaluation of Bond Strength of Acrylic Teeth to Denture Base using Different
      Polymerization Techniques: A Comparative Study.
AB  - BACKGROUND: Acrylic teeth have long been used in the treatment of a complete
      denture. One of the primary advantages of acrylic teeth is their ability to
      adhesively bond to the denture base resins. Although the bonding seems
      satisfactory, however, bond failures at the acrylic teeth and denture base resin
      interface are still a common clinical problem in prosthodontics. The purpose of
      this study was to evaluate the bond strength of acrylic teeth to denture base
      using different polymerizing techniques. MATERIALS AND METHODS: Acrylic resin
      teeth were bonded to heat cure acrylic resin and were polymerized by conventional
      water bath and microwave energy. The samples are then retrieved from the flask;
      trimmed and polished. The samples were then subjected to tensile forces till
      failure by using the Instron Universal testing machine. The machine used a direct
      pull on the incisal portion of the lingual surface in a labial direction at a
      height above the denture base resin bar with a crosshead speed of 0.5 mm/min.
      RESULTS: In the present study, it was found that conventionally cured specimens
      exhibited higher bond strength than microwave cured specimens and majority of
      fractures occur within the body of the tooth. It was found that debonding occurs
      within the body of the tooth rather than tooth acrylic interface, so there is no
      need of surface treatment of ridge lap surface. CONCLUSION: Conventionally cured
      specimens possess statistically higher bond strength than microwave cured
      specimens.

PMID- 26225107
TI  - Shaping Ability of 5(th) Generation Ni-Ti Rotary Systems for Root Canal
      Preparation in Curved Root Canals using CBCT: An In Vitro Study.
AB  - BACKGROUND: Various root canal systems are available commercially with each
      manufacturer stating superior characteristics of their respective systems. Fifth
      generation root canal systems claim to have better flexibility and superior
      debris elimination due to their offset design. This study aims to compare the
      effects of fifth generation rotary systems on canal curvature, transportation and
      centering ratio of curved mesial root canals of mandibular molar via cone-beam
      computed tomographic (CBCT) imaging. MATERIALS AND METHODS: A total of 60
      mandibular first molars with an angle of curvature ranging from 20 to 40 degrees 
      of the mesiobuccal root were divided into three groups with 20 canals each.
      Before instrumentation, the groups were balanced with respect to the angle and
      radius of canal curvature based on CBCT images taken. All root canals were shaped
      to an apical size of 25: OneShape (OS) (Micro Mega, Besancon, France), ProTaper
      Next X2 (PTN) (Dentsply Maillefer), Revo S(RS) (Micro Mega, Besancon, France).
      CBCT assessment was done post instrumentation. SPSS version 16 software was used
      for statistical analysis. The significance level was set at P = 0.05. RESULTS:
      The OS system maintained better canal centricity and less transportation as
      compared to PTN and RS. There was no significant difference among the three
      groups in canal curvature after instrumentation. CONCLUSIONS: All file systems
      used straightened the root canal curvature similarly. OS instrumentation
      exhibited superior performance compared with the RS and PTN systems with respect
      to transportation and centering ratio.

PMID- 26225108
TI  - Comparative Evaluation of Push Out Bond Strength of a Fiber Post System using
      Four Different Resin Cements: An In-Vitro Study.
AB  - BACKGROUND: Debonding is one of the frequent causes of failure experienced in
      fiber-reinforced composite posts, and establish along post space-dentin adhesive
      interface. The purpose of this study was to assess push-out bond strength of a
      fiber-reinforced post system using four different resin cements. MATERIALS AND
      METHODS: In this in-vitro study 40 mandibular premolars were decoronated, and
      roots were treated endodontically. Following the post space preparation, the
      roots were grouped into four groups of 10 specimens each. Fiber-reinforced
      composite posts were cemented with four resin cement systems: (a) Multilink
      Speed, (b) Rely X Unicem, (c) Calibra, and (d) Permaflo DC. Three sections of
      each root, with a thickness of 3 mm, were prepared. The push-out test was with a
      universal testing machine at a crosshead speed of 1 mm/min, and bond strength
      values were evaluated. The data were analyzed with using multivariate analysis of
      variance (MANOVA) and post-hoc Scheffe test. RESULT: The mean push-out bond
      strength was highest for Rely X Unicem (18.0 +/- 1.81), followed by Multilink
      Speed (13.1 +/- 0.75) and Permaflo DC (12.8 +/- 0.95). The lowest mean push-out
      bond strength was seen with Calibra (11.8 +/- 0.69). There were statistically
      significant differences seen in the push-out bond strength of resin cement in
      different root canal regions using MANOVA and post-hoc Scheffe test. CONCLUSION:
      Mean push-out bond strength was highest for Rely X Unicem, followed by Multilink
      Speed and Permaflo DC. Lowest mean push-out bond strength was seen with respect
      to Calibra.

PMID- 26225109
TI  - A Fatal Outcome of Rhino-orbito-cerebral Mucormycosis Following Tooth Extraction:
      A Case Report.
AB  - Rhino-orbito-cerebral mucormycosis is an uncommon aggressive life-threatening
      opportunistic fungal infection that affects mainly the immunocompromised
      population with mortality rate up to 50%. Due to its aggressive nature, early
      detection and prompt management are of great importance for a good prognosis. Our
      report describes a fatal outcome of a case of rhino-orbito-cerebral mucormycosis
      following tooth extraction in an uncontrolled non-insulin-dependent diabetes
      mellitus patient after 14 days of admission.